PMID- 15713959
TI  - Complementary, alternative therapies should face rigorous testing, IOM concludes.

PMID- 15713960
TI  - Do increases in the market share of managed care influence quality of cancer care
      in the fee-for-service sector?
AB  - BACKGROUND: Increases in the market share of managed care in an area are
      associated with decreases in expenditures in the fee-for-service sector (i.e., a
      spillover effect). Given concerns that these decreases in expenditures result
      from reductions in necessary care, we examined associations between increases in
      managed care market share and changes in the quality of care delivered to cancer
      patients in the fee-for-service sector. METHODS: We studied a population-based
      sample of fee-for-service Medicare beneficiaries aged 66 years or older who were
      diagnosed with breast (N = 41,394) or colorectal (N = 48,027) cancer during 1993
      1999. We used fixed effects regression analysis of SEER cancer registry and
      Medicare claims data to assess whether county-level increases in the market share
      of managed care over time were associated with the quality of cancer care. All
      statistical tests were two-sided. RESULTS: Increases in the market share of
      managed care were not associated with most quality indicators, including receipt
      of surveillance mammography after diagnosis for patients with breast cancer (P =
      .83), receipt of radiation after breast-conserving surgery among women who
      underwent breast-conserving surgery (P = .16), receipt of adjuvant chemotherapy
      for patients with stage III colorectal cancer (P = .94), or surveillance
      colonoscopy after treatment for colorectal cancer (P = .39). Increases in the
      market share of managed care were associated with increased rates of surveillance
      carcinoembryonic antigen testing for colorectal cancer patients (P = .001).
      CONCLUSIONS: Increases in managed care market share had limited or no effect on
      the quality of care for cancer patients. Concerns that increases in managed care
      would have large negative spillover effects on the quality of cancer care appear
      to be unfounded; however, the potential for managed care to stimulate improved
      quality throughout the medical care system have not yet been realized.

PMID- 15713961
TI  - Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a
      prospective study in men.
AB  - BACKGROUND: Although chronic infection with hepatitis B virus (HBV) has been
      established as a cause of hepatocellular carcinoma (HCC), the roles of viral load
      and HBV genotype remain unclear. METHODS: From 1988 through 1992, baseline blood
      samples were collected from 4841 Taiwanese men who were HBV carriers but had not
      been diagnosed with HCC. We used real-time polymerase chain reaction assays of
      plasma DNA samples to quantify HBV DNA levels (a measure of viral load) and
      determine HBV genotypes for 154 case patients who were diagnosed with HCC during
      14 years of follow-up and 316 control subjects. Unconditional logistic regression
      was used to assess odds ratios (ORs) of HCC for HBV-related factors. All
      statistical tests were two-sided. RESULTS: The risk of HCC increased with
      increasing HBV viral load (adjusted OR for the highest versus the lowest quintile
      of HBV DNA copies/mL = 7.26, 95% confidence interval [CI] = 3.54 to 14.89;
      P(trend)<.001). Genotype C HBV was associated with an increased risk of HCC
      compared with other HBV genotypes (adjusted OR = 5.11, 95% CI = 3.20 to 8.18).
      Both viral load and genotype were positively associated with HCC within 10-year
      age categories among subjects aged 30 years old to older than 60 years. Genotype
      C HBV was associated with increased viral load, and associations of HBV genotype
      and viral load with HCC risk were additive. The adjusted OR of HCC for those
      carrying genotype C HBV and with viral load in the highest quintile was 26.49
      (95% CI = 10.41 to 67.42) compared with HBV carriers with other HBV genotypes and
      viral load in the lowest two quintiles. CONCLUSIONS: Measurements of HBV viral
      load and genotype may help to define which male HBV carriers aged 30 years or
      older are at high risk for HCC.

PMID- 15713962
TI  - Detection of hypermethylated genes in women with and without cervical neoplasia.
AB  - BACKGROUND: DNA methylation changes are an early event in carcinogenesis and are
      often present in the precursor lesions of various cancers. We examined whether
      DNA methylation changes might be used as markers of cervical intraepithelial
      neoplasia (CIN) and invasive cervical cancer (ICC). METHODS: We used methylation
      specific polymerase chain reaction (PCR) to analyze promoter hypermethylation of
      20 genes, selected on the basis of their role in cervical cancer, in 319
      exfoliated cell samples and matched tissue biopsy specimens collected during two
      studies of Senegalese women with increasingly severe CIN and ICC (histology
      negative/atypical squamous cells of undetermined significance [ASCUS] = 142, CIN
      1 = 39, CIN-2 = 23, CIN-3/carcinoma in situ [CIS] = 23, ICC = 92). Logic
      regression was used to determine the best set of candidate genes to use as
      disease markers. All statistical tests were two-sided. RESULTS: Similar promoter
      methylation patterns were seen in genes from exfoliated cell samples and
      corresponding biopsy specimens. For four genes (CDH13, DAPK1, RARB, and TWIST1),
      the frequency of hypermethylation increased statistically significantly with
      increasing severity of neoplasia present in the cervical biopsy (P<.001 for
      each). By using logic regression, we determined that the best panel of
      hypermethylated genes included DAPK1, RARB, or TWIST1. At least one of the three
      genes was hypermethylated in 57% of samples with CIN-3/CIS and in 74% of samples
      with ICC but in only 5% of samples with CIN-1 or less. The estimated specificity
      of the three-gene panel was 95%, and its sensitivity was 74% (95% confidence
      interval [CI] = 73% to 75%) for ICC and 52% (95% CI = 49% to 55%) for CIN-3/CIS.
      By extrapolation, we estimated that, among Senegalese women presenting to
      community-based clinics, detection of the DAPK1, RARB, or TWIST1 hypermethylated
      gene would reveal histologically confirmed CIN-3 or worse with a sensitivity of
      60% (95% CI = 57% to 63%) and a specificity of 95% (95% CI = 94% to 95%).
      CONCLUSIONS: Aberrant promoter methylation analysis on exfoliated cell samples is
      a potential diagnostic tool for cervical cancer screening that potentially may be
      used alone or in conjunction with cytology and/or human papillomavirus testing.

PMID- 15713963
TI  - Coffee, tea, and caffeine consumption and incidence of colon and rectal cancer.
AB  - BACKGROUND: Frequent coffee consumption has been associated with a reduced risk
      of colorectal cancer in a number of case-control studies. Cohort studies have not
      revealed such an association but were limited in size. We explored the
      association between consumption of coffee and tea and the incidence of colorectal
      cancer in two large prospective cohorts of women and men. METHODS: We used data
      from the Nurses' Health Study (women) and the Health Professionals' Follow-up
      Study (men). Consumption of coffee and tea and total caffeine intake were
      assessed and updated in 1980, 1984, 1986, 1990, and 1994 among women and in 1986,
      1990, and 1994 among men. The incidence of cancer of the colon or rectum was
      ascertained through 1998. Hazard ratios were calculated using Cox proportional
      hazards models that adjusted for potential confounders. All tests of statistical
      significance were two-sided. RESULTS: During almost 2 million person-years of
      follow-up, 1438 cases of colorectal cancer were observed. Consumption of
      caffeinated coffee or tea with caffeine or caffeine intake was not associated
      with the incidence of colon or rectal cancer in either cohort. For both cohorts
      combined, the covariate-adjusted hazard ratio for colorectal cancer associated
      with consumption of each additional cup of caffeinated coffee was 0.99 (95%
      confidence interval [CI] = 0.96 to 1.03). However, participants who regularly
      consumed two or more cups of decaffeinated coffee per day had a 52% (95% CI = 19%
      to 71%) lower incidence of rectal cancer than those who never consumed
      decaffeinated coffee. CONCLUSIONS: Consumption of caffeinated coffee, tea with
      caffeine, or caffeine was not associated with incidence of colon of rectal
      cancer, whereas regular consumption of decaffeinated coffee was associated with a
      reduced incidence of rectal cancer.

PMID- 15713964
TI  - Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a
      prospective study in Japan.
AB  - BACKGROUND: An association between coffee drinking and reduced risk of liver
      cancer has been suggested by animal studies, but epidemiologic evidence of such
      an association in a high-risk population is lacking. We conducted a large-scale
      population-based cohort study of the association between coffee drinking and
      hepatocellular carcinoma (HCC) in a Japanese population. METHODS: Newly diagnosed
      case patients (250 men and 84 women) with HCC were identified from a 10-year
      follow-up of the Japan Public Health Center-based Prospective Study, which
      consists of 90,452 middle-aged and elderly Japanese subjects (43,109 men and
      47,343 women). Case patients were grouped according to coffee intake and were
      stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and
      previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and
      95% confidence intervals (CIs) for HCC were calculated with Cox proportional
      hazards modeling. All statistical tests were two-sided. RESULTS: Subjects (men
      and women combined) who consumed coffee on a daily or almost daily basis had a
      lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36
      to 0.66]); risk decreased with the amount of coffee consumed (compared with
      nondrinkers, the HR for 1-2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3-4
      cups per day = 0.48 [95% CI = 0.28 to 0.83]; for > or =5 cups per day = 0.24 [95%
      CI = 0.08 to 0.77], P(trend) < .001). The risk of liver cancer in almost never
      drinkers in this population was 547.2 cases per 100,000 people over 10 years, but
      it was 214.6 cases per 100 000 people with drinking coffee on a daily basis. The
      inverse association persisted when the participants were stratified by lifestyle
      factors. Similar associations were observed when the analysis was restricted to
      hepatitis C virus-positive patients (all daily drinkers compared with
      nondrinkers: HR =0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive
      patients (HR = 0.60 [95% CI = 0.31 to 1.18]) and to subjects with no past history
      of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67]). CONCLUSIONS: In the
      Japanese population, habitual coffee drinking may be associated with reduced risk
      of HCC.

PMID- 15713965
TI  - Zinc concentration in esophageal biopsy specimens measured by x-ray fluorescence
      and esophageal cancer risk.
AB  - BACKGROUND: In rodents, zinc deficiency potentiates the effects of certain
      nitrosamines that act as esophageal carcinogens. Studies of the association
      between zinc and esophageal squamous cell carcinoma in humans have been hampered
      by plasma zinc homeostasis, which obscures individual differences in total zinc
      stores, and by the uncertainty regarding zinc bioavailability when estimating
      dietary zinc intake because phytate from whole grains effectively prohibits zinc
      absorption. By using baseline tissue biopsy specimens collected in a prospective
      observational study, we determined the association between incident esophageal
      squamous cell carcinoma and baseline element concentrations in tissue sections
      from residents of Linzhou, China, participating in a nutrition intervention
      trial. METHODS: We used x-ray fluorescence spectroscopy to measure zinc, copper,
      iron, nickel, and sulfur concentrations in single 5-microm-thick sections from
      formalin-fixed, paraffin-embedded esophageal biopsy specimens collected in 1985
      from 60 eventual case and 72 control subjects. Subjects were matched on baseline
      histology and followed for 16 years. We used Cox proportional hazards models to
      estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the
      association between each element and risk of incident esophageal cancer. All
      statistical tests were two-sided. RESULTS: The risk of developing esophageal
      cancer was much lower for subjects in the highest quartile of esophageal tissue
      zinc concentration compared with those in the lowest quartile (HR = 0.21, 95% CI
      = 0.065 to 0.68). The association was statistically significant across quartiles
      (P(trend) = .015). Individuals in the highest quartile of sulfur concentration
      had a lower risk of esophageal cancer than individuals in the lowest quartile (HR
      = 0.29, 95% CI = 0.095 to 0.85), but the association across quartiles was not
      statistically significant (P(trend) = .081). There was no association between
      copper, iron, or nickel concentrations and risk of esophageal cancer. CONCLUSION:
      High tissue zinc concentration was strongly associated with a reduced risk of
      developing esophageal squamous cell carcinoma. X-ray fluorescence spectroscopy
      can be used to assess relationships among concentrations of both nutritional and
      toxic elements and disease risk in banked tissue specimens.

PMID- 15713966
TI  - Signal in noise: evaluating reported reproducibility of serum proteomic tests for
      ovarian cancer.
AB  - Proteomic profiling of serum initially appeared to be dramatically effective for
      diagnosis of early-stage ovarian cancer, but these results have proven difficult
      to reproduce. A recent publication reported good classification in one dataset
      using results from training on a much earlier dataset, but the authors have since
      reported that they did not perform the analysis as described. We examined the
      reproducibility of the proteomic patterns across datasets in more detail. Our
      analysis reveals that the pattern that enabled successful classification is
      biologically implausible and that the method, properly applied, does not classify
      the data accurately. We show that the method used in previously published studies
      does not establish reproducibility and performs no better than chance for
      classifying the second dataset, in part because the second dataset is easy to
      classify correctly. We conclude that the reproducibility of the proteomic
      profiling approach has yet to be established.

PMID- 15713967
TI  - Importance of communication between producers and consumers of publicly available
      experimental data.
AB  - The application of mass spectrometry to discover new cancer biomarkers is in its
      infancy. Many of these new markers are low-abundance proteins that exist as
      fragments associated with carrier proteins. Although reproducibility is key to
      the use of mass spectrometry for ion fingerprint analysis, the scientific
      community has yet to establish a common platform or standardized operating
      procedures that are necessary for intra- and inter-laboratory comparison. In an
      effort to assist others who are perfecting mass spectrometry platforms for
      profiling, ongoing experimental data were posted for public consumption. An
      unintended consequence of unrestricted access to experimental data is the risk of
      inappropriate conclusions drawn and publicly disseminated that could have been
      avoided by communication between the producers and consumers of the data. Such
      disputes, however, should not divert us from the validation of this promising new
      approach.

PMID- 15713968
TI  - Lessons from controversy: ovarian cancer screening and serum proteomics.
AB  - In 2002 a study reported that a blood test, based on pattern-recognition
      proteomics mass spectroscopy analysis of serum, was nearly 100% sensitive and
      specific to detect ovarian cancer. Plans to introduce a commercial screening test
      by early 2004 were delayed amid concerns about whether the approach was
      reproducible and reliable. In this issue of JNCI, two commentaries discuss
      whether the initial results are reproducible and whether bias may account for
      results. This essay describes how threats to validity from chance and bias may
      cause erroneous results and inflated expectations in the kind of observational
      research being conducted in several "-omics" fields to assess molecular markers
      for diagnosis and prognosis of cancer. To address such threats and to realize the
      potential of new -omics technology will require application of appropriate rules
      of evidence in the design, conduct, and interpretation of clinical research about
      molecular markers.

PMID- 15713969
TI  - Re: Association between biallelic and monoallelic germline MYH gene mutations and
      colorectal cancer risk.

PMID- 15713970
TI  - Re: Corporations flock to selling for the (breast cancer) cure.

PMID- 15713971
TI  - Bioethics: an emerging discipline.

PMID- 15713973
TI  - Need for constant monitoring of dengue infections.

PMID- 15713972
TI  - Carbohydrate diets, postprandial hyperlipidaemia, abdominal obesity and Asian
      Indians: a recipe for atherogenic disaster.

PMID- 15713974
TI  - Genetic alteration in drug resistance markers of Plasmodium falciparum.
AB  - Plasmodium falciparum shows plasticity in its genome. For its survival it can
      delete certain genes (or portions) if not needed for its growth and has the
      capability to regulate its genes under various stages of its life cycle as well
      as under unfavourable environmental conditions. Parasite shows enormous amount of
      antigenic variation under immune pressure leading to the emergence of vaccine
      resistant strains. Similarly, under drug pressure it allows mutations to settle
      in the target genes. It is becoming more and more clear that with the continuous
      exposure to a drug, the parasite accumulates more and more number of mutations in
      these genes. By measuring the number of these point mutations among field
      isolates one can predict the efficacy of a particular drug. Therefore, these
      markers are useful tools at epidemiological level. This molecular surveillance
      can also help in slowing down the drug resistance if supported by a careful drug
      usage policy. Further studies are required to develop molecular markers for rest
      of the antimalarial drugs as well as the improvement on the existing molecular
      tools for accurate and rapid detection of drug resistant malaria.

PMID- 15713975
TI  - Carbohydrate-induced hypertriglyceridaemia among West Indian diabetic and non
      diabetic subjects after ingestion of three local carbohydrate foods.
AB  - BACKGROUND AND OBJECTIVE: Studies suggest that the link between postprandial
      hyperglycaemia and cardiovascular risk in type 2 diabetes mellitus might be
      related to postprandial hypertriglyceridaemia and the increased levels of the
      highly atherogenic small and dense low density lipoprotein (LDL) particles. In
      this study we therefore aimed to determine which of the three popular
      carbohydrate foods has the highest potential of increasing postprandial
      triglyceride levels in type 2 diabetic patients and in healthy non diabetic
      individuals. METHODS: All subjects were studied on three different occasions
      seven days apart after an overnight fast. On each day of study, anthropometric
      indices were measured and after collecting fasting blood sample, subjects
      consumed bread, roti or rice within 10 min and water taken as wished.
      Subsequently, 7 ml of venous blood samples were collected at 60, 90, 120 and 150
      min for insulin, glucose and lipids determinations. RESULTS: The diabetic and non
      diabetic healthy subjects had similar baseline body mass index, insulin,
      triglyceride, total and LDL-cholesterol. The mean percentage triglyceride
      increase after ingestion of the test foods was highest with bread and lowest with
      rice irrespective of diabetic status or ethnicity, and despite similar baseline
      triglyceride, insulin and body mass index levels, the diabetic patients of East
      Indian origin had comparatively higher incremental triglyceride levels for the
      three test foods than those of African origin. INTERPRETATION AND CONCLUSION:
      Contrary to anecdotal perception, the commercially prepared whole wheat bread has
      the highest propensity to induce hypertriglyceridaemia especially among diabetic
      patients of East Indian origin.

PMID- 15713976
TI  - Validity of Queen's College Step Test for estimation of maximum oxygen uptake in
      female students.
AB  - BACKGROUND AND OBJECTIVES: Maximum oxygen uptake (VO(2) max) is internationally
      accepted parameter to evaluate the cardiorespiratory fitness. But determination
      of VO(2)max is restricted within well equipped laboratory because of its
      exhausting, hazardous and complicated experimental protocol. Various attempts
      have been made to enumerate indirect and easy protocols for prediction of
      VO(2)max but such record is unavailable in Indian women. The present study was
      conducted to validate the applicability of Queen's College Step Test (QCT) for
      indirectly estimating the maximum oxygen uptake in female sedentary university
      students. METHODS: Forty sedentary female university students of same socio
      economic background were recruited by simple random sampling from University of
      Calcutta, Kolkata. VO(2)max of each participant was determined by direct
      procedure and indirect QCT method with a gap of four days in between the tests.
      Direct estimation of VO(2)max comprised incremental bicycle exercise followed by
      expired gas analysis by Scholander micro-gas analyzer whereas VO(2)max was
      indirectly predicted by standard protocol of QCT. RESULTS: The difference between
      the mean VO(2)max values directly measured and indirectly predicted (PVO(2)max)
      was statistically significant (P<0.001). Limit of agreement analysis revealed
      poor confidence level for application of current method of QCT in the studied
      population. VO(2)max value exhibited significant correlation (r = -0.83, P<0.001)
      with QCT pulse rate. For precise and reliable estimation of VO(2)max in the
      studied population a new equation was computed. INTERPRETATION AND CONCLUSION:
      Our results suggest that QCT in its original form cannot be applied due to its
      poor agreement with the direct method but can be applied with the modified
      equation in this population to evaluate maximum oxygen uptake, especially when
      large numbers of participants are to be tested in absence of a well equipped
      laboratory.

PMID- 15713977
TI  - Serodiagnosis of dengue during an outbreak at a tertiary care hospital in Delhi.
AB  - Dengue, an important human arboviral infection, is endemic in many parts of
      India. Outbreaks are now reported quite frequently from different parts of the
      country. We report here findings of serological investigation of serum samples
      received during a recent outbreak of dengue infection in Delhi from September to
      November 2003. Acute phase serum samples from suspected cases of dengue infection
      (including dengue fever, dengue haemorrhagic fever and dengue shock syndrome) of
      duration 5 days, were tested for dengue specific IgM antibodies by enzyme linked
      immuno sorbant assay (ELISA). Of the 874 serum samples tested, 456 (52.3% ) were
      positive for dengue specific IgM antibodies. The maximum number of positive cases
      was reported in October, peaking in second and third week. Patients in the age
      group of 21-30 yr accounted for 34.2 per cent of positive cases. This outbreak
      was less severe as compared to the previous 1996 outbreak and showed a shift
      towards an older age group.

PMID- 15713978
TI  - Postnatal development of alcohol dehydrogenase in liver and intestine of rats
      exposed to ethanol in utero.
AB  - BACKGROUND AND OBJECTIVES: Ethanol exposure during gestation induces marked
      aberrations in growth and development of offsprings collectively known as foetal
      alcohol syndrome (FAS);. However, its effects on the postnatal development of
      alcohol dehydrogenase (ADH) are not adequately investigated. Therefore, ADH
      activity in liver and intestine of rats exposed to ethanol during gestation was
      studied in relation to postnatal development. METHODS: Pregnant female rats
      beginning at day 1 of gestation were fed 1 ml of 30 per cent ethanol daily during
      the entire gestation period. ADH activity was determined in liver and intestine
      postnatally at day 4, 8, 14, 20 and 30. DNA and RNA contents and intestinal
      histology were also examined. RESULTS: During the first two weeks of postnatal
      life, there was no difference in ADH levels of rat liver and intestine in control
      and prenatally ethanol exposed pups but ADH levels were significantly reduced at
      3-4 wk in ethanol fed group compared to control. A similar decrease in DNA and
      RNA contents of intestine and changes in tissue morphology were observed in
      ethanol exposed pups during postnatal development. INTERPRETATION AND CONCLUSION:
      The findings of our study suggested that prenatal ethanol exposure modified ADH
      activity in liver and intestine during postnatal development. This could affect
      ethanol metabolism under these conditions.

PMID- 15713979
TI  - The role of p53 and anaplastic lymphoma kinase genes in the progression of
      cutaneous CD30(+) lymphoproliferative diseases.
AB  - BACKGROUND AND OBJECTIVES: Molecular events that precede transformations from
      lymphomatoid palulosis (LyP) to mycosis fungoides (MF) or to cutaneous anaplastic
      large cell lymphoma (ALCL) in the CD 30(+) cutaneous lymphoproliferative diseases
      (LPDs) are not known. Altered p(53) gene may be responsible since overexpression
      of the p(53) gene product has been reported in higher, but not in lower grades of
      cutaneous lymphomas. Expression of the anaplastic lymphoma kinase (ALK) gene
      product has also been described as an important prognostic indicator in ALCL. ALK
      positive systemic nodal ALCL are associated with a good prognosis. However,
      primary cutaneous ALCL that are ALK negative have a better overall survival. The
      current study was done to see if mutated p(53) gene or ALK reactivity were poor
      prognostic indicators in those patients with CD 30(+) cutaneous LPD who showed
      progression of the disease. METHODS: Mutations of the p(53) gene and expression
      of the ALK gene product were analysed in 36 patients (23 of LyP and 13 of CD30(+)
      cutaneous ALCL). Follow up data were available up till 5 yr in all patients.
      RESULTS: Clinical progression or histological transformation in sequential biopsy
      specimens was found in 9 of 36 patients. Transformation occurred in 5 patients (4
      from LyP to ALCL and 1 from MF to ALCL) and clinical progression in 4 patients
      with ALCL. Mutations of the p(53) gene were found in two biopsy specimens of LyP.
      ALK gene products were not detected in any of the biopsy specimens of LyP and
      primary cutaneous ALCL. INTERPRETATION AND CONCLUSION: Although 9 of 36 patients
      with cutaneous CD30(+) LPDs had progression of their disease, neither mutations
      of the p(53) gene nor ALK immunoreactivity were found in any of these biopsies.
      The two cases of LyP that had mutated p(53) gene in their biopsy specimens showed
      no progression of their disease in the 5 yr follow up period. It appears that
      these molecular events may not play any significant role in the pathogenesis,
      progression or transformation of cutaneous CD30(+) LPD.

PMID- 15713980
TI  - Evaluation of bifenthrin treated mosquito nets against anopheline and culicine
      mosquitoes.
AB  - BACKGROUND AND OBJECTIVES: The main rural malaria vector Anopheles culicifacies
      has developed resistance to dichloro diphenyl trichloroethane (DDT), hexachloro
      cyclo hexane (HCH) and malathion in the state of Haryana in northern India. An
      alternative synthetic pyrethroid insecticide bifenthrin was therefore evaluated
      on mosquito nets against anopheline and culicine mosquitoes, in two villages
      Jagdishpur and Garh Mirakpur of Community Health Center (CHC) Badhkhalsa in
      district Sonipat, Haryana state. METHODS: Two formulations of bifenthrin,
      suspension concentrate (SC) and micro-emulsion (ME) were compared with micro
      capsule suspension (CS) of lambdacyhalothrin. The impact of three doses of
      bifenthrin (10, 25 and 50 mg/m(2)) impregnated on mosquito nets was compared with
      lambdacyhalothrin (25 mg/m(2)) and untreated control. Quality assessment of
      treatment on treated nets was carried out by residue analysis and the persistence
      of the insecticide on nets was determined by contact bioassays. Efficacy of
      treated nets on mosquito density was assessed by calculating mosquito entry rate,
      immediate mortality, delayed mortality and excito-repellency to the insecticides.
      RESULTS: In susceptibility tests An. culicifacies was susceptible to bifenthrin
      (0.1% test papers) and to lambdacyhalothrin (0.05% test papers). Bioassays on
      treated nets against A. culicifacies recorded 100 per cent mortality up to tenth
      fortnight for all the doses of impregnation with bifenthrin (SC and ME) and
      lambdacyhalothrin (CS). Ring-net bioassays against An. culicifacies showed median
      knock-down time between 3.1 to 11.4 min. Behavioural indices were also studied
      for anopheline and culicine mosquitoes. The reduction in entry rates of
      anopheline and culicine mosquitoes into the rooms with treated nets compared to
      control indicated good efficacy with all the formulations and doses of the
      insecticides. INTERPRETAION AND CONCLUSION: Indoor (immediate) mortality of
      mosquitoes with bifenthrin ME formulation was relatively lower compared to SC
      fomulation of bifenthrin and based on delayed mortility and continued
      susceptibility in bioassays, bifenthrin ME at the rate of 10 mg/m(2) dose was
      found suitable for the impregnation of mosquito nets for phase III trial.

PMID- 15713981
TI  - Profile of bacterial isolates from patients with ventilator associated pneumonias
      in a tertiary care hospital in India.

PMID- 15713983
TI  - Novel treatments for drug-induced toxic epidermal necrolysis (Lyell's syndrome).
AB  - Drug-induced toxic epidermal necrolysis (TEN) is a life-threatening disease
      characterized by extensive destruction of the epidermis. It apparently results
      from the formation of specific toxic drug metabolites by the keratinocytes. The
      mortality rate which averages 25-30% is mainly due to secondary septicemia, and
      to ionic and metabolic disturbances following loss of epidermal integrity.
      Apoptosis is the likely mechanism leading to massive keratinocyte death in TEN.
      Dysregulations in the tumor necrosis factor-alpha (TNF-alpha) pathway, CD95
      system (Fas ligand, CD95L; Fas receptor, CD95R) and calcium homeostasis in the
      epidermis are involved in this apoptotic process. An active role has also been
      ascribed to T lymphocytes, macrophages and factor XIIIa-positive dermal
      dendrocytes. Despite progress, treatment of TEN remains controversial. In the
      past, systemic glucocorticoids were used in order to target the inflammatory
      reaction in TEN. However, there was no evidence for improvement of the healing
      process, while corticosteroids worsened the prognosis by increasing the risk of
      septicemia. Only a few cases have been treated with other drugs including
      cyclophosphamide, pentoxyfilline, thalidomide, anti-TNF-alpha antibodies and
      cyclosporin A. In the recent past, some TEN patients were treated with
      intravenous human immunoglobulins (IVIG). The rationale for such a treatment was
      to block the CD95 system on keratinocytes. The early promising clinical results
      of IVIG treatment in TEN were subsequently challenged. This review compares the
      effectiveness and drawbacks of the major drugs presently used in TEN treatment.
      Some future prospects in TEN management are also discussed.

PMID- 15713984
TI  - Immunoglobulin replacement therapy in primary antibody deficiency diseases-
      maximizing success.
AB  - Antibody or humoral immunodeficiencies comprise the largest group of primary
      immunodeficiency diseases. Since the first description of patients with low
      gammaglobulin levels more than four decades ago, a great wealth of information
      has been accumulated. Especially in the last several years, the application of
      molecular and genetic techniques has unraveled many of these disorders,
      identifying disorders of B cell development, failure of class switch
      recombination and abnormalities of specific antibody production. Regardless of
      the underlying defect, the mainstay of therapy has been and remains
      immunoglobulin (Ig) replacement therapy, currently by intravenous infusion or
      subcutaneous injection. With advances in manufacturing, a number of products are
      not only safe for intravenous administration but doses can be increased to
      provide even more effective infection prophylaxis. However, manufacturing
      processes, methods of viral inactivation and removal and final composition differ
      widely among the available preparations. How these variables impact clinical
      outcome is not clear, but they have the potential to do so. As a result, careful
      selection of an intravenous immunoglobulin (IVIG), matching patient needs and
      risks to those risks associated with a specific IVIG, is necessary to optimize
      outcomes and maximize the success of Ig replacement therapy.

PMID- 15713985
TI  - In vitro analysis of birch-pollen-associated food allergy by use of recombinant
      allergens in the basophil activation test.
AB  - BACKGROUND: Basophil activation is associated with the expression of CD63. In
      birch-pollen-associated food allergy to celery, carrot and apple, Bet v 1, Api g
      1, Dau c 1 and Mal d 1 are major allergens. Recombinant allergens have not yet
      been used in the CD63-based basophil activation test (BAT). OBJECTIVE: To
      evaluate the feasibility of using recombinant allergens in the BAT in the
      diagnosis of allergy to apple, carrot and celery and to compare results with
      routine tests, i.e. skin prick tests (SPTs) and specific IgE. METHODS: Thirty-two
      patients with an oral allergy syndrome induced by apple, carrot or celery and 22
      controls were studied. SPTs were performed with native foods. Specific IgE was
      determined by the CAP method and basophil activation by flowcytometry upon double
      staining with anti-IgE/anti-CD63 monoclonal antibodies after incubating with
      purified recombinant Bet v 1, Bet v 2, Api g 1, Dau c 1 and Mal d 1. RESULTS: By
      the combined use of the BAT and the CAP method, sensitization to Bet v 1 and Bet
      v 2 was detected in 100 and 25% of all subjects, respectively. Sensitivity of
      specific IgE for apple, carrot and celery was 60, 70 and 75% with corresponding
      specificities of 64, 86 and 82%. Sensitivity of the BAT for Mal d 1, Dau c 1 and
      Api g 1 was 75, 65 and 75% with corresponding specificities of 68, 100 and 77%.
      CONCLUSIONS: The BAT using recombinant allergens provides a valuable new in vitro
      method for the detection of sensitization to foods. Although double-blind placebo
      controlled food challenges remain the gold standard to confirm food allergy, the
      CD63-based BAT with recombinant allergens may supplement routine tests for
      allergy diagnosis.

PMID- 15713986
TI  - Chronic mild hyperhomocysteinemia induces aortic endothelial dysfunction but does
      not elevate arterial pressure in rats.
AB  - Mild hyperhomocysteinemia is prevalent in the general population and has been
      linked to endothelial dysfunction and high arterial pressure (AP) in clinical
      studies. The present study was designed to determine whether a rise in AP was
      induced by mild hyperhomocysteinemia and whether the potential rise in AP is
      secondary or prior to endothelial dysfunction. Experiments were performed in a
      rat model of mild hyperhomocysteinemia induced by oral administration of
      homocysteine for 1-4 months. Aortic endothelial dysfunction was observed 2 months
      after homocysteine treatment while endothelium-independent vasodilation was
      normal. In parallel, homocysteine treatment increased phenylephrine-induced
      contraction in aortas with endothelium, but did not modify the contraction in
      aortas without endothelium, suggesting a decrease of basal NO production. In
      conscious unrestrained rats, AP was not significantly different 1, 2, 3 and 4
      months after homocysteine treatment. In correlation, endothelial function of a
      resistance vessel (mesenteric artery), mainly non-NO nonprostanoid factor
      mediated, was preserved, indicating that homocysteine treatment only affected the
      NO pathway. In conclusion, mild hyperhomocysteinemia alone is not sufficient to
      elevate arterial blood pressure, at least in the rat model. Aortic endothelial
      dysfunction produced by mild hyperhomocysteinemia is independent of hemodynamic
      factors.

PMID- 15713987
TI  - Prevention of irinotecan-induced diarrhea by oral sodium bicarbonate and
      influence on pharmacokinetics.
AB  - Alkalization of the intestinal tract by oral administration of sodium bicarbonate
      has been reported to be a promising method for preventing delayed diarrhea, a
      dose-limiting toxicity in patients receiving chemotherapy with irinotecan
      hydrochloride. However, it is feared that this method may adversely affect the
      pharmacokinetics of irinotecan by inhibiting its intestinal absorption and that
      of its active metabolites. We compared the pharmacokinetics and toxicity of
      irinotecan with and without oral alkalization in a cross-over study that enrolled
      10 colorectal cancer patients. We found that alkalization did not decrease the
      blood levels of irinotecan and its active metabolite. In fact, the area under
      concentration versus time curves (AUCs) of irinotecan and 7-ethyl-10
      hydroxycamptothecin glucuronide (SN-38G) were statistically equivalent both with
      and without oral alkalization. Also, the AUC of SN-38 with alkalization was
      statistically equivalent or larger than that without alkalization. Oral
      alkalization reduced the incidence of diarrhea and gastrointestinal symptoms, and
      these adverse effects were not worsened by long-term administration. These
      results suggest that oral alkalization can control diarrhea and gastrointestinal
      toxicity without decreasing the blood levels of irinotecan and its active
      metabolites, thus improving the tolerability of long-term chemotherapy without
      reducing efficacy.

PMID- 15713988
TI  - Raltitrexed plus gemcitabine (TOMGEM) in advanced pancreatic cancer. Results of a
      Belgian multicentre phase II study.
AB  - OBJECTIVES: This multicenter phase II study was designed to determine the
      activity and tolerance of gemcitabine and raltitrexed in advanced pancreatic
      adenocarcinoma. PATIENTS AND METHODS: Thirty-three chemonaive patients with
      measurable disease received the TOMGEM regimen consisting of Raltitrexed 3
      mg/m(2) in 15 min followed by Gemcitabine 1,000 mg/m(2) in 30 min on day 1,
      Gemcitabine alone 1,000 mg/m(2) on day 8 and repeated on day 21. RESULTS: Thirty
      three patients (median age: 62; locally advanced/metastatic disease: 5/28) were
      enrolled; the total number of cycles administered was 173 (median: 4). There were
      10 partial response (confirmed), 2 stable disease (SD) >/=24 weeks, 7 SD <24
      weeks, and 14 progressive disease for a response rate of 30.3% (95% CI: 14-46%);
      a clinical benefit was observed in 8/30 patients assessed (30%); median duration
      of response was 9.1 months. National Cancer Institute Common Toxicity Criteria
      grade III or IV neutropenia/thrombocytopenia were observed in 42 and 12% of the
      patients, respectively. Relevant nonhematological toxicities (grade III-IV) were
      rare although one toxic death was observed. Median time to progression was 2.8
      months; one-year survival was 21%; median survival was 4.7 months. CONCLUSION:
      Our data suggest that the combination of raltitrexed/gemcitabine is a very
      convenient regimen with an acceptable toxicity, and is active in advanced
      pancreatic cancer.

PMID- 15713989
TI  - The reproducibility of a binary tumor grading system for uterine endometrial
      endometrioid carcinoma, compared with FIGO system and nuclear grading.
AB  - OBJECTIVE: A binary grading system has been proposed to assess the amount of
      solid growth, the pattern of invasion, and the presence of necrosis, and thereby
      divide endometrial endometrioid carcinomas into low- and high-grade tumors. We
      analyzed this system for predicting the prognosis, with respect to inter- and
      intraobserver reproducibility and treatment modalities. METHODS: A total of 200
      endometrial carcinomas, based on hysterectomy specimens, were graded according to
      the binary grading system, for comparison against The International Federation of
      Gynecology and Obstetrics (FIGO) system and nuclear grading. RESULTS: Both inter-
      and intraobserver agreement using the binary grading system (kappa = 0.57;
      percent agreement: 82% and kappa = 0.62; 84%) were superior compared with the
      FIGO system (0.50; 60% and 0.62; 73%) and the nuclear grading (0.23; 49% and
      0.43; 65%). Patients with early-stage low-grade tumors had a 98% rate for 5-year
      survival (5YS). Patients with early-stage high-grade tumors, and those with
      advanced-stage low-grade tumors, had respectively 86% to 87% rates for 5YS. But
      patients with advanced-stage high-grade tumors had a 49% rate for 5YS. In binary
      low-grade early-stage tumors, the patient outcome was better with no adjuvant
      therapy and chemotherapy, compared with other therapies. CONCLUSION: A binary
      grading system was superior to others in permitting greater reproducibility and
      predicting the prognosis of endometrial cancer patients.

PMID- 15713990
TI  - Higher farnesyl diphosphate synthase activity in human colorectal cancer
      inhibition of cellular apoptosis.
AB  - OBJECTIVE: Farnesyl diphosphate synthase (FPPs) produces FPP which is considered
      a branch-point intermediate in the synthesis of sterols and isoprenylated
      cellular metabolites. In this study we investigated whether detectable FPPs
      activity was present in human colorectal cancer (CRC), also evaluating in vitro
      the role of this enzyme in the growth and apoptosis of CRC cells by using
      Pamidronate (PAM), a FPPs activity inhibitor. METHODS: The activity level of FPPs
      was determined in CRC and the normal surrounding mucosa of 50 patients by
      radiochemical assay. The FPPs mRNA expression was investigated in 15 of 50
      patients by quantitative reverse transcriptase polymerase chain reaction (RT
      PCR). K-ras mutation was evaluated using PCR and restriction enzyme analysis.
      Cell growth and apoptosis, after PAM treatment, in human CRC cell line DLD-1 were
      measured by MTT test and DNA fragmentation, respectively. RESULTS: FPPs activity
      was detectable in human CRC. FPPs activity and its mRNA were significantly more
      abundant in cancer samples than in normal mucosa. In vitro PAM resulted in a
      significant reduction of cell growth and also gave rise to a marked proapoptotic
      effect. CONCLUSIONS: This study provides the first evidence of the presence of
      FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant
      role in colon cancer proliferation.

PMID- 15713991
TI  - Increased serum CA-15.3 levels in patients with megaloblastic anemia due to
      vitamin B12 deficiency.
AB  - OBJECTIVES: To estimate the usefulness of serum tumor markers' monitoring, as
      predictors of gastric cancer in patients with pernicious anemia. PATIENTS AND
      METHODS: We investigated serum levels of carcinoembryonic antigen (CEA), alpha
      fetal protein, cancer antigen (CA)-19.9, CA-125 and CA-15.3 in 50 patients with
      pernicious anemia and in 24 healthy controls, matched for age and sex. In 38
      patients, the evaluation was repeated 1-6 months after the correction of
      cobalamin deficiency. RESULTS: All patients and controls had normal serum CEA and
      alpha-FP, and the levels of these markers as well as those of CA-125 and CA-19.9
      did not differ between the two groups. All 50 patients, but only 2 controls
      exhibited increased serum CA-15.3, and the difference between the two groups was
      very significant (129.4 +/- 84.9 vs. 19.8 +/- 7.3 IU/ml, p < 0.001), while no
      difference between males and females was found. A thorough clinical examination
      of all patients, and mammographic study in 18 females did not reveal any finding
      suspicious of breast cancer. CA-15.3 levels were positively correlated with serum
      lactate dehydrogenase, and negatively with B(12) and hemoglobin, but they were
      substantially decreased after the correction of anemia, in all 38 patients
      tested, and in 33 of them they were restored to normal. After a median follow-up
      of 34 months, one patient developed a colon cancer, but none showed any sign
      suspicious of breast cancer. CONCLUSIONS: Serum CA-15.3 shows an aberrant
      increase in untreated patients with pernicious anemia, which is reversed after
      the correction of the anemia. The possible origin seems unrelated to mammary
      tissue, and may be released by the apoptosing bone marrow megaloblastic
      erythroblasts.

PMID- 15713992
TI  - Dose escalation of busulfan with pentoxifylline and ciprofloxacin in patients
      with breast cancer undergoing autologous transplants.
AB  - OBJECTIVE: There is evidence that pentoxifylline (PTX) and ciprofloxacin (Cipro)
      may protect patients from the effects of chemotherapy and radiation, which could
      allow further drug dose escalation. This study was conducted to determine whether
      oral and intravenous (IV) PTX and Cipro permits increased dose levels of oral
      busulfan (BU) with a fixed dose of IV cyclophosphamide (CY) in patients with
      breast cancer receiving autologous or syngeneic hematopoetic cell
      transplantation. METHODS: Sixty-seven patients received PTX and Cipro with CY of
      150 mg/kg and escalating doses of BU. The BU dosing began at 15 mg/kg, escalating
      in 1 mg/kg increments in groups of 4 patients. If no grade 3 or 4 regimen-
      related toxicities (RRT) were observed, the next 4 patients were treated at a
      higher dose. RESULTS: Excessive RRT was not observed until BU 21 mg/kg was
      reached. Two patients at this dose level had RRTs and their BU steady-state
      concentration (Css) were 1,414 and 1,545 ng/ml. At a BU dose of 20 mg/kg ,
      average BU Css 1,280 ng/ml, 0/4 had RRT. Among 10 patients who had BU Css
      targeted to 1,350 ng/ml, RRTs occurred in 2 (20%). CONCLUSIONS: In this
      preliminary study with PTX and Cipro, the maximum tolerated dose of BU that can
      be given with CY (150 mg/kg) was 20 mg/kg, a BU Css of approximately 1,300 ng/ml.
      A randomized trial is necessary to determine whether PTX and Cipro reduce the
      toxicities of this regimen.

PMID- 15713993
TI  - Gemcitabine combined with oxaliplatin (GEMOX) as second-line chemotherapy in
      patients with advanced ovarian cancer refractory or resistant to platinum and
      taxane.
AB  - OBJECTIVES: The aim of this multicenter feasibility study was to determine the
      toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin
      combination as second-line treatment in platinum plus paclitaxel
      resistant/refractory advanced ovarian cancer. METHODS: Twenty patients received a
      30-60-min infusion of gemcitabine a week for 2 weeks, followed by 120-180 min
      infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m(2),
      respectively. Seventeen cases (85% of the total) were platinum resistant and 3
      (15%) were platinum refractory. RESULTS: Grade 3/4 thrombocytopenia occurred in
      14/20 of cases (70%); there were no symptomatic cases. 2 patients required
      platelet transfusion and 8 patients received hydrocortisone. The dose- limiting
      toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in
      8/20 (40%) of cases (no sepsis was registered). Five patients were treated with
      recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF
      prophylactically from the first cycle. The overall response rate of the
      combination in terms of antitumor activity was 26% (95% CI = 9-51%). CONCLUSION:
      A combination of gemcitabine and oxaliplatin using this schedule gave rise to a
      moderate/severe toxicity profile and would be feasible only if growth factors
      were used and/or gemcitabine were administered at lower doses. The antitumor
      activity of the combination was insufficient reward for the resultant toxicity
      profile. However, equivalent to that of other drugs used in platinum refractory
      and resistant patients.

PMID- 15713994
TI  - Clinicopathological features of extranodal lymphomas: Kuwait experience.
AB  - A total of 935 patients with extranodal non-Hodgkin lymphoma (NHL) diagnosed in
      the period between January 1985 and December 2000 in Kuwait Cancer Center,
      serving the whole population of Kuwait, were used to describe the
      clinicopathological and epidemiological features of extranodal lymphomas in
      Kuwait. Extranodal lymphomas accounted for 45% of all NHL observed during this
      time. All NHL cases from Kuwait Cancer registry were analyzed and pathologically
      reclassified using the latest WHO (2000) classification. The most common lymphoma
      observed was diffuse large B-cell lymphoma (58.60%) followed by Burkitt s
      lymphoma (BL) (3.80%). In the pediatric group, BL comprises more than two thirds
      of all patients (77.20%). The most common extranodal sites were stomach (19.70%)
      and skin (17.80%) in the adult group, large intestine (29.80%) and small
      intestine (19.30%) in the pediatric age group. The majority (73.40%) of adult
      extranodal lymphomas was in stage IE-IIE and had a very good prognosis. On the
      contrary, the majority of pediatric extranodal lymphomas were found to be in
      stage III and IV. Variations in treatment policies (single agent or combined
      chemotherapy, radiotherapy, combined modality treatment) adopted and changed
      during the time period of 16 years of this retrospective study were documented.

PMID- 15713995
TI  - The cost of treatment of skeletal-related events in patients with bone metastases
      from lung cancer.
AB  - PURPOSE: Patients with bone metastases from lung cancer often experience skeletal
      related events (SREs) including pathological fracture, spinal cord compression,
      hypercalcemia or pain requiring surgery, radiotherapy or opioid analgesics. These
      complications result in impaired mobility and reduced quality of life and have a
      significant negative impact on survival. The economic consequences of SREs in
      patients with lung cancer have not been examined. METHODS: We conducted a
      retrospective analysis using a large US health insurance claims database to
      estimate the incidence and costs of treatment of SREs in patients with bone
      metastases of lung cancer treated in a naturalistic setting. Study subjects had
      >/=2 encounters with a diagnosis of primary lung cancer and >/=2 encounters with
      a diagnosis of metastases to bone. SREs were identified based on the occurrence
      on or after the date of first diagnosis of bone metastases, of (1) >/=1 encounter
      with a diagnosis of pathological fracture, spinal cord compression or
      hypercalcemia, (2) >/=1 bone surgery or radiotherapy procedure, or (3) the
      initiation of opioid analgesic therapy. Survival and costs of SRE-related care in
      patients with SREs were estimated using Kaplan-Meier methods. RESULTS: We
      identified 534 patients with lung cancer and bone metastases, including 295 (55%)
      with >/=1 SRE. Radiotherapy (68%) and fracture (35%) were the most common SREs.
      Median survival after the first identified SRE was 4.1 months (95% confidence
      interval: 3.6-5.5 months). The estimated lifetime SRE-related cost per patient
      was USD 11,979 (95% confidence interval: USD 10,193-13,766). Radiotherapy
      accounted for the greatest proportion of cost (61%) by SRE type. CONCLUSION: The
      economic burden of SREs in patients with bone metastases of lung cancer is
      substantial. Intravenous bisphosphonates, such as zoledronic acid, which have
      been shown to prevent these events, may reduce these costs.

PMID- 15713996
TI  - S100A4 expression is an early event of papillary carcinoma of the thyroid.
AB  - OBJECTIVES: S100A4 is a calcium-binding protein related to the metastatic
      potential of carcinoma. In order to elucidate its contribution to the progression
      of thyroid carcinoma, we investigated S100A4 expression in various thyroid
      neoplasms. METHODS: We immunohistochemically examined S100A4 expression in 195
      cases of thyroid neoplasms. RESULTS: Although S100A4 was absent in normal
      follicular cells and follicular adenoma, S100A4 was positive in all 115 cases of
      papillary carcinoma examined, including 58 microcarcinomas. However, a
      significant relationship could not be established between S100A4 expression and
      clinicopathological features of papillary carcinoma. In follicular carcinoma, the
      widely invasive type expressed S100A4 more frequently than the minimally invasive
      type (p = 0.0028). In anaplastic carcinoma, S100A4 was expressed in 61.9% of
      cases, but the incidence was significantly lower (p < 0.0001) than that in
      papillary carcinoma. CONCLUSIONS: These findings suggest that (1) S100A4 plays a
      constitutive role in papillary carcinoma and (2) S100A4 may be a useful marker
      for early the detection of this carcinoma.

PMID- 15713997
TI  - The effect of Edrecolomab (Mo17-1A) or fluorouracil-based chemotherapy on
      specific immune parameters in patients with colorectal cancer. A comparative
      study.
AB  - OBJECTIVES: We investigated the immune profile of patients with resected Dukes'
      stage C colorectal cancer (CRC), receiving adjuvant therapy with edrecolomab
      (Mo17-1A) or first-line 5-fluorouracil (5-FU)-based chemotherapy. PATIENTS AND
      METHODS: Patients received either 5 doses of Mo17-1A over 13 weeks, or 5
      FU/leucovorin, or 5-FU/levamisole over 6 and 12 months, respectively. Peripheral
      blood was collected postoperatively and 4 months after therapy initiation.
      Peripheral blood mononuclear cells were tested in the autologous mixed lymphocyte
      reaction (AMLR), for natural killer (NK) and lymphokine-activated killer (LAK)
      cell activity. Serum cytokines were quantified by ELISA. RESULTS: Fifty-two
      patients entered the study. Postoperatively, they exhibited decreased levels of
      interleukin (IL)-2, interferon-gamma, IL-12, granulocyte-macrophage colony
      stimulating factor and IL-15, low cellular immune responses (AMLR, NK- and LAK
      cytotoxicity) and increased levels of IL-1beta, tumor necrosis factor-alpha, IL
      6, IL-10 and prostaglandin E(2). After four months of therapy, patients receiving
      edrecolomab demonstrated enhanced AMLR, NK, LAK activity, increased serum levels
      of cytokines regulating such responses and reduced levels of acute-phase
      cytokines and immune suppressors, compared to patients treated with conventional
      chemotherapy. CONCLUSIONS: Postoperative adjuvant therapy with edrecolomab
      restores the in vivo deficient immune responses of patients with resected Dukes'
      C CRC despite its clinical ineffectiveness in recent randomized adjuvant trials.
      These results suggest that further immunological studies with the combination of
      edrecolomab and chemotherapy are required.

PMID- 15713998
TI  - The expression of a type II transmembrane serine protease (Seprase) in human
      gastric carcinoma.
AB  - OBJECTIVE: The invasion and metastasis of carcinoma cells require the proteolytic
      degradation of the extracellular matrix by various cell surface proteases. Among
      these, seprase is a type II transmembrane serine protease absent in normal
      tissues and it has been implicated in the invasion of the extracellular matrix by
      both tumor and stromal cells in human breast carcinoma and melanoma. In the
      present study, the expression of seprase mRNA, protein and its gelatin-degrading
      activity in human gastric carcinoma were examined to substantiate the potential
      role of seprase in gastric carcinoma invasion. METHODS: We have examined the
      seprase expression in human gastric carcinoma (n = 34) by RT-PCR, Western
      immunoblotting analysis, immunohistochemistry, and gelatin zymography. RESULTS:
      Immunoblotting analysis using mAb D8 directed against seprase showed that the
      carcinoma tissues in 26 out of 34 cases of gastric cancer expressed a dimeric
      form of seprase but their normal counterparts did not. Gelatin zymography
      confirmed that the isolated seprase exhibited the gelatin-degrading activity and
      was active. Seprase-expressing carcinoma tissues were more often found in the
      scirrhous type than in other types of gastric carcinoma. RT-PCR analysis showed
      that seprase mRNA was present in carcinoma tissues but not in normal tissues.
      Immunohistochemically, seprase was mainly located in gastric carcinoma cells,
      weakly in stromal cells and microvessel endothelial cells in the tumor nest, and
      none in normal cells. CONCLUSIONS: Our studies showed the unique expression and
      localization of seprase in the tumor and stromal cells within human gastric
      carcinoma but not in normal tissues, suggesting a role of seprase in the invasive
      and metastatic progression of gastric carcinoma.

PMID- 15713999
TI  - Divergent patterns of allelic alterations in premalignant laryngeal lesions
      indicate differences in the impact of morphological grading characteristics.
AB  - OBJECTIVES: Classic histological grading and molecular genetic analysis of
      epithelial hyperplastic laryngeal lesions (EHLL) were correlated in an attempt to
      elucidate, which classic marker reflects best the gradual progression of
      laryngeal premalignant lesions as determined by an increasing number of molecular
      genetic aberrations. METHODS: Thirty-two EHLL were grouped according to four
      grades of nuclear atypia, four degrees of epithelial maturation and three groups
      of overall and suprabasal mitotic activity. Overall and suprabasal proliferative
      activity were measured by MIB-1 immunostaining and staged according to four
      levels. Allelic imbalance was determined by PCR using 32 microsatellite loci at
      nine chromosomal arms. RESULTS: Of the six classic criteria, only progressive
      mitotic indices correlated with allelic alterations in a remarkable variety of
      microsatellite markers, especially at chromosome 17p. CONCLUSION: Using the
      number of allelic alterations as standard for assessment, this preliminary study
      gives first evidence that certain morphological criteria could reflect
      differently the gradual progression of premalignant laryngeal lesions with
      mitotic index being the most promising marker. Further studies with long-term
      follow-up are required to prove the predictive value of these criteria in daily
      practice.

PMID- 15714000
TI  - Reduction in p48-ISGFgamma levels confers resistance to interferon-alpha2a in
      MHCC97 cells.
AB  - OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most prevalent
      malignancies in China and, due to the limited efficacy of currently available
      therapies, is responsible for a large number of deaths. IFN-alpha therapy has
      shown promise in the treatment of various forms of human cancer and is considered
      in the treatment of HCC. Previous results from our group showed that high doses
      of IFN-alpha exert a significant antiproliferative effect on MHCC97 human
      xenografts in nude mice, but not on MHCC97 cells when tested in vitro. Here we
      present experiments designed to characterize the molecular mechanism underlying
      the defective response of MHCC97 cells to IFN-alpha. Elucidation of the mechanism
      underlying the defective response of MHCC97 to IFN-alpha may help to explain and
      possibly to overcome clinical failures of this form of tumor therapy. METHODS:
      IFN-alpha(2a) was administered between 3,000 and 10,000 IU/ml, a range strongly
      inhibiting proliferation in other cell lines. Gene expression profiles of MHCC97
      cells were obtained before and after treatment with IFN-alpha(2a) using cDNA
      microarray analysis. The transcriptional activity of relevant genes responding to
      IFN-alpha(2a) in the cDNA microarray experiments was confirmed by RT-PCR and
      Northern blot analysis. Transient transfection with an expression vector was used
      to restore p48-ISGFgamma (IRF9) protein levels. Cell proliferation was evaluated
      using the MTT assay. RESULTS: Although IFN-alpha treatment caused the activation
      of several signal transduction pathways in MHCC97 cells, the lack of an
      antiproliferative effect was found to mainly derive from a defect in the
      activation of the transcription factor ISGF3 required for Jak/STATS signaling. We
      show that the defect in ISGF3 activation is mainly caused by the absence of one
      of its essential components, the protein p48-ISGFgamma from MHCC97 cells. Indeed,
      transient expression of p48-ISGFgamma restores sensitivity to IFN-alpha(2a).
      Although the mRNA levels of p48-ISGFgamma were normal in MHCC97 cells, mutations
      could be detected in the gene coding for the protein. We hypothesize, therefore,
      that these mutations alter the message or protein stability, leading to the
      reduced protein levels observed. CONCLUSION: Our results confirm the important
      role of Jak/STATS signaling in the antiproliferative effects of IFN-alpha in
      tumor cells and indicate that defects in ISGF3 can cause resistance to IFN
      alpha(2a) treatment.

PMID- 15714001
TI  - Cell density modulates the metastatic aggressiveness of a mouse colon cancer cell
      line, colon 26.
AB  - OBJECTIVE: Although cell density in cultured cells has demonstrated several
      alterations in the nature of cell kinetics, the changes in the metastatic
      aggressiveness of cancer lines under different cell densities have not yet been
      studied. METHODS: In the current study, we investigated the influence of changing
      the cell density of cultured cancer cells (colon 26 and B16-F10) injected into
      the tail vein in BALB/c mice on the metastatic activity by evaluating the number
      of lung metastases, and the possible mechanisms of this phenomenon were discussed
      based on the basis of the results of an invasion assay and a cell adhesion assay.
      RESULTS: The number of metastatic nodules was significantly higher in the high
      density group than in the low one in colon 26 (p < 0.005), however, this
      phenomenon was not seen in B16-F10. Next, we performed the same experiment by
      changing the environment to the opposite conditions for the cells in the low- and
      high-density groups, and the results showed the metastatic activities to be
      always higher in the high-density group. Moreover, although no difference was
      seen regarding the invasive activity between the high- and low-density groups, an
      adhesion assay showed the difference in the adhesion cell rate to be
      significantly higher in the high-density group especially in early period after
      coculture with human umbilical vein endothelial cells (HUVEC) (p < 0.05).
      CONCLUSION: In some cell types, the metastatic activity could be altered and
      reversed by changing the environment, such as the cell density, during a
      relatively short period. As a result, the epigenetic changes of cancer cells are
      thus suggested to play a certain role in the malignant potentiality.

PMID- 15714002
TI  - ERK, PKC and PI3K/Akt pathways mediate extracellular ATP and adenosine-induced
      proliferation of U138-MG human glioma cell line.
AB  - OBJECTIVE: Extracellular nucleotides and nucleosides induce proliferation in a
      set of human glioma cell lines. In this study we investigate the signal
      transduction pathways involved in ATP and adenosine-mediated proliferation in
      U138-MG human glioma cells. METHODS: Cell proliferation was accessed through
      [(3)H]thymidine incorporation, cell counting and flow cytometry. Protein
      phosphorylation was detected through Western blotting. RESULTS: ATP or adenosine
      (100 microM) induced extracellular signal-regulated protein kinase (ERK), Akt and
      GSK3beta phosphorylation. The increase in [(3)H]thymidine incorporation induced
      by ATP or adenosine was decreased when cells were incubated with LY 294002 (by +/
      90%), GF 109203X (by +/-76%) or PD 098059 (by +/-63%). The increase in cell
      numbers with ATP or adenosine was less after a 48-hour treatment of cells with
      ATP or adenosine plus GF 109203X (by +/-66%) or LY 294002 (by +/-83%). Percentage
      of cells in S phase was decreased in cells treated with LY 294002 plus ATP when
      compared to ATP- treated cells. CONCLUSION: Stimulation of purinergic receptors
      in U138-MG cells leads to cell proliferation mediated by PI3K/Akt, ERK and PKC
      signaling. It may be clinically important for pharmacological intervention in
      gliomas to associate purinergic receptor antagonists and signal transduction
      pathways blockers.

PMID- 15714003
TI  - Centrosome hyperamplification and chromosomal damage after exposure to radiation.
AB  - OBJECTIVE: In order to elucidate the effects of radiation on centrosome
      hyperamplification (CH), we examined the centrosome duplication cycle in KK47
      bladder cancer cells following irradiation. METHODS: KK47 cells were irradiated
      with various doses of radiation and were examined for CH immunostaining for gamma
      tubulin. RESULTS: Nearly all control cells contained one or two centrosomes, and
      mitotic cells displayed typical bipolar spindles. The centrosome replication
      cycle is well regulated in KK47. Twenty-four hours after 5-Gy irradiation,
      approximately 80% of irradiated cells were arrested in G2 phase, and at 48 h
      after irradiation, 56.9% of cells contained more than two centrosomes. Laser
      scanning cytometry performed 48 h after irradiation showed the following two
      pathways: (1) unequal distribution of chromosomes to daughter cells, or (2)
      failure to undergo cytokinesis, resulting in polyploidy. With mitotic collection,
      M-phase cells with CH could be divided into G1 cells with micronuclei and
      polyploidal cells. Fluorescence in situ hybridization analysis showed clear signs
      of chromosomal instability (CIN) at 48 h after irradiation. The present study had
      two major findings: (1) continual duplication of centrosomes occurred in the cell
      cycle-arrested cells upon irradiation, leading to centrosome amplification; (2)
      cytokinesis failure was due to aberrant mitotic spindle formation caused by the
      presence of amplified centrosomes. Abnormal mitosis with amplified centrosomes
      was detected in the accumulating G2/M population after irradiation, showing that
      this amplification of centrosomes was not caused by failure to undergo
      cytokinesis, but rather that abnormal mitosis resulting from amplification of
      centrosomes leads to cytokinesis block. CONCLUSION: These results suggest that CH
      is a critical event leading to CIN following exposure to radiation.

PMID- 15714004
TI  - Thalidomide inhibits the growth and progression of hepatic epithelioid
      hemangioendothelioma.
AB  - Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the
      liver with an unpredictable malignant potential. Its growth can lead to hepatic
      failure, extrahepatic metastasis and death. Surgical resection or liver
      transplantation is the treatment of choice if metastasis is not identified.
      Several antineoplastic agents have been proposed for cases of nonresectable HEH.
      We report the case of a 52-year-old patient with HEH metastatic to the lungs who
      was successfully treated with oral thalidomide therapy.

PMID- 15714005
TI  - Germline mutation of the LKB1/STK11 gene with loss of the normal allele in an
      aggressive breast cancer of Peutz-Jeghers syndrome.
AB  - Peutz-Jeghers syndrome (PJS) is an autosomal-dominant polyposis disorder with an
      increased risk of multiple cancer. The LKB1/STK11 gene, which acts as a tumor
      suppressor, is responsible for PJS and plays a role in suppressing breast cancer.
      The low expression of LKB1/STK11 in sporadic breast cancer is significantly
      associated with shorter survival. Here we describe a PJS patient with aggressive
      breast cancer that carried not only a germline mutation of LKB1/STK11 but also
      loss of the normal allele. The combination of these mutations may be associated
      with the poor prognosis of this patient. To our knowledge, we are the first to
      show that a germline mutation causing PJS is combined with the loss of the
      homologous normal allele of LKB1/STK11 in breast cancer.

PMID- 15714006
TI  - [H]BQ-123 binding to native endothelin ET(A) receptors in human astrocytoma
      1321N1 cells and screening of potential ligands.
AB  - Endothelin ET(A) receptors on the human astrocytoma 1321N1 cell line were
      characterized in radioligand binding studies using the ET(A)-selective antagonist
      radioligand [(3)H]BQ-123. A membrane preparation of the cell line showed a high
      expression level of ET(A) receptors (B(max) = 128 fmol/mg protein). The K(D)
      value for [(3)H]BQ-123 (K(D) = 2.29 nmol/l) was comparable to that previously
      determined at the human neuroblastoma cell line SK-N-MC. The specific labeling of
      ET(A) receptors on astrocytoma 1321N1 cells by [(3)H]BQ-123 was confirmed by
      determining the rank order of potency of a series of agonists and antagonists. A
      competition assay for the screening of potential ET(A) ligands was established
      and a series of new disubstituted imidazo[1,2-c]pyrimidine and pyrimido[1,6
      a]pyrimidine derivatives was investigated. Moderate ET(A) affinity was detected
      for several derivatives [30-40% inhibition of [(3)H]BQ-123 binding (3 nmol/l) at
      a concentration of 10 micromol/l]. Astrocytoma 1321N1 cells natively express
      relatively high levels of ET(A) receptors. They are useful for the screening of
      potential ET(A) ligands in radioligand binding assays with [(3)H]BQ-123.

PMID- 15714007
TI  - Functional, structural, and neuronal alterations in urinary bladder during
      diabetes: investigations of a mouse model.
AB  - Urinary bladder dysfunction is a common complication in diabetes, but the
      mechanisms involved are undefined and treatment options are limited. Murine
      models provide opportunities to utilize transgenic technologies for bladder
      research and here we investigate the functional, structural and neuronal aspects
      of the bladder in a mouse model of type-1 diabetes. Mice were injected with
      streptozotocin (150 mg/kg) or vehicle and studied at 5 weeks. Increases in blood
      glucose and total urine output were observed. In vitro cystometry showed a 2-fold
      increase in bladder capacity and compliance and decreased intravesical plateau
      pressure in diabetics versus controls. Bladder structure and composition were
      evaluated by digital imaging; region-specific changes included increased smooth
      muscle and urothelium and no change in collagen content. Alterations in
      cholinergic, adrenergic and nitric oxide-related functional responsiveness were
      also observed. The prevalence of cholinergic and adrenergic neuronal tracts was
      determined by immunohistochemistry: decreased vesicular acetylcholine transferase
      was observed in smooth muscle, whereas tyrosine hydroxylase was increased in the
      lamina propria, demonstrating a 'neuronal remodeling' shift toward pro-relaxant
      neuronal pathways. These studies demonstrate that this mouse model of diabetes
      exhibits important features of urinary bladder remodeling that are similar to the
      findings in humans and other animal models and will therefore be useful for
      further mechanistic investigations.

PMID- 15714008
TI  - Catatonia: disappeared or under-diagnosed?
AB  - BACKGROUND: Over the last century, especially during the latter half, the
      prevalence of the diagnosis of catatonic schizophrenia decreased considerably.
      Several explanations for this phenomenon have been put forward. SAMPLING AND
      METHODS: The present study investigated the frequency of the diagnosis of
      catatonic schizophrenia in a large sample of admitted psychiatric patients (n =
      19,309). In addition, the presence of catatonic symptoms was studied in a sample
      of patients with schizophrenia (n = 701) and in a group of consecutively admitted
      psychotic patients (n = 139). In these two groups the effect of the diagnostic
      procedures on the recognition of catatonia was examined. RESULTS: The diagnosis
      of catatonic schizophrenia dropped from 7.8% in 1980-1989 to 1.3% in 1990-2001 (p
      < 0.001). In addition, a possible under-diagnosis of catatonic schizophrenia was
      found in an independent sample of patients with schizophrenia. Application of a
      systematic catatonia rating scale in patients admitted with acute psychosis
      identified a bimodally distributed catatonic dimension. At least 18% of these
      patients fulfilled the criteria for catatonia. Interestingly, the catatonic
      subgroup used atypical antipsychotic compounds more frequently (p < 0.05).
      CONCLUSIONS: The results suggest that changes in diagnostic criteria and the
      diagnostic procedure itself are responsible for the under-recognition of
      catatonia.

PMID- 15714009
TI  - Perceived relationships with parents and paranoid delusions: comparisons of
      currently ill, remitted and normal participants.
AB  - BACKGROUND: Paranoid delusions are associated with abnormal attributions and
      abnormal beliefs about the self. Some researchers have also reported an
      association between paranoid beliefs and abnormal attachment representations.
      SAMPLING AND METHODS: Perceptions of relationships with the family of origin were
      measured in 14 currently ill paranoid patients, 9 remitted paranoid patients and
      15 healthy controls, using two methods: the Parental Bonding Instrument (PBI),
      and the Relationship with Family of Origin Scale (REFAMOS), an interview-based
      assessment. RESULTS AND CONCLUSIONS: On the PBI, both currently ill and remitted
      patients reported low parental care and overprotectiveness during childhood.
      Similar negative accounts of relationships with parents during the 16-20 years
      age period, and also at the time of assessment, were elicited from both the ill
      and remitted patients on the REFAMOS. These findings might reflect the influence
      of illness on patients' perceptions of their parents. However, the fact that the
      remitted patients did not differ from the currently ill patients raises the
      possibility that dysfunctional relationships are a common feature of the history
      of paranoid patients, perhaps contributing to the development of paranoid
      thinking.

PMID- 15714010
TI  - Diagnostic stability in depressive disorder as according to ICD-10 in clinical
      practice.
AB  - BACKGROUND: The diagnostic stability of the ICD-10 diagnosis of depressive
      disorder has not been investigated in clinical practice. SAMPLING AND METHODS:
      All patients who were diagnosed with depressive disorder at least once in a
      period from 1994 to 2002 in psychiatric out- or inpatient settings in Denmark
      were identified in a nationwide register. RESULTS: A total of 39,741 patients
      were diagnosed with depressive disorder at least once; among these, 81% were
      diagnosed at the first contact. In approximately 56% of patients, the initial
      diagnosis of depressive disorder eventually changed during follow-up mainly to
      the schizophrenic spectrum (16%), but also to personality disorders (9%),
      neurotic, stress-related and somatoform disorders (8%) and to bipolar disorder
      (8%). Among the 18% of patients who were later diagnosed with depressive
      disorder, 23% initially had a diagnosis of adjustment disorder. CONCLUSIONS: When
      the ICD-10 diagnoses are used in clinical practice, the diagnosis of depressive
      disorder has a low stability over time. These findings emphasize the need for a
      longitudinally based diagnostic process in the diagnostic systems.

PMID- 15714011
TI  - Indication for psychotherapy in offspring of a parent affected by a chronic
      somatic disease (e.g. multiple sclerosis).
AB  - Based on the transcripts of video-recorded, semi-structured interviews with 41
      offspring (aged 6-18 years) of parents with multiple sclerosis, we evaluated the
      indication for psychotherapy. These results were then compared with the
      previously determined coping ability of each child/adolescent. Psychotherapy was
      indicated for 22 out of the 41 children/adolescents. There was a significant
      relation between the indication for psychotherapy and the children's inability to
      cope with the parental disease. The present findings confirm the risk of mental
      health problems in children of somatically ill parents. In our sample, half of
      the children and adolescents were estimated to benefit from individual
      psychotherapy, which might enhance their ability to cope with the parental
      illness.

PMID- 15714013
TI  - Peer review for advanced practice nurses: what does it really mean?
AB  - Peer review has multiple manifestations and purposes. Two stated purposes are the
      demonstration of professionalism and clinical competency. The American Nurses
      Association (ANA) defines nursing peer-review as a process for evaluating the
      care provided by an individual according to accepted standards. Further, the ANA
      proposes that nurses with similar rank and clinical expertise should conduct
      these evaluations. Some local jurisdictions may also mandate that advanced
      practice nurses (APNs) review one another's care. Therefore, APNs should become
      familiar with sources for evaluation criteria and tool formats for APN peer
      review. The advantages and limitations of the various formats and processes of
      peer review should also be considered.

PMID- 15714014
TI  - Credentialing for nurse practitioners: an update.
AB  - The public has the right to safe, quality healthcare delivered by professionals
      with the appropriate education, training, and experience. The Joint Commission on
      Accreditation of Healthcare Organizations, the Accreditation Association for
      Ambulatory Healthcare, and managed care organizations take this commitment very
      seriously. One mechanism required by these agencies to ensure patient safety is
      the process of credentialing and delineation of clinical privileges for medical
      staff and allied health professionals, such as Acute Care Nurse Practitioners.
      This commitment extends to patients receiving healthcare through the technology
      of telemedicine and to those requiring emergency care resulting from trauma,
      disasters, and varying forms of terrorism. In addition, safeguards must be in
      place to prevent identity theft of healthcare providers, including Acute Care
      Nurse Practitioners. It is essential that Acute Care Nurse Practitioners be
      familiar with the regulations that impact and guide the process of credentialing
      and obtaining clinical privileges in a variety of venues.

PMID- 15714015
TI  - Capturing reimbursement for advanced practice nurse services in acute and
      critical care: legal and business considerations.
AB  - Advanced practice nurses (APNs) have been affected positively and negatively by
      recent changes in the way hospitals are financed. Among these changes are the
      shift from cost-based reimbursement to a prospective payment system and increased
      opportunities for billing APN services under the physician payment system.
      Positive effects include the need for hospitals to decrease the length of stay of
      hospitalized patients, leading to jobs for APNs who make the hospital course and
      discharge more efficient. Negative effects include budget shortfalls that lead to
      layoffs. This article explains the current financial landscape, including
      phenomena that are impeding the billing of APN services, and recommends
      adjustments so that the APN role will be on firm financial footing.

PMID- 15714016
TI  - Evidenced-based practice: priorities and implementation strategies.
AB  - Evidenced-based practice (EBP) should be a driving force behind establishing
      optimal clinical practices. Recently, clinicians and hospitals have started
      efforts to introduce key EBP. These efforts hold the potential to improve patient
      outcomes and reduce costs. However, many practices need updating with EBP. Which
      ones should be chosen? While practices often vary in terms of importance for each
      hospital, some changes in practice are likely to have a better return on the
      investment (ROI). Two key areas affecting most hospitals are practices associated
      with high costs and increased mortality. In critical care areas, these two key
      areas often involve addressing outlier management and severe sepsis. In addition,
      the recognition of the need for the change is only one step in ensuring EBP. To
      ensure EBP is implemented, clinical leaders who will ensure that the new practice
      standards are being utilized are necessary. Fortunately, many hospitals have
      strong leaders. The advanced practice nurse (APN) is one such leader. The APN is
      often in a unique position to help recognize, prioritize, and implement EBP into
      the hospitals culture. This article illustrates steps in making EBP a reality by
      highlighting the management of outliers and severe sepsis and the implementation
      strategies for these conditions.

PMID- 15714017
TI  - Assessing outcomes in advanced practice nursing practice: the use of quality
      indicators and evidence-based practice.
AB  - Advanced practice nurses (APNs) impact both patient care and healthcare systems
      on a daily basis. Tracking and documenting the outcomes of APN practice have
      become essential, due partly to the emphasis on outcomes that has become a
      component of the majority of healthcare initiatives. This article outlines
      important aspects related to assessing outcomes and discusses the use of quality
      indicators to demonstrate outcomes of APN practice. Examples from clinical
      practice are provided in order to demonstrate that assessing the outcomes of APN
      practice can be incorporated into daily practice as part of ongoing initiatives.
      In delineating the outcomes of APN care, the value of APNs can be formally
      acknowledged.

PMID- 15714018
TI  - Creating an advanced practice nurse-friendly culture: a marathon, not a sprint.
AB  - Advanced practice nurses (APNs) have extraordinary opportunities in acute and
      critical care settings. However, new obstacles accompany these opportunities and
      these obstacles can needlessly hamper APN practice and reduce the APN's
      contributions to patient care. Contributions by APNs can be maximized by
      deliberately and thoughtfully creating a practice culture that is APN-friendly.
      This article analyzes eight characteristics important to creating the APN
      friendly culture: clarity of vision and values, commitment, communication,
      collaboration, credibility, contributions, confidence, and complexity. Creating
      an APN-friendly culture is a worthwhile organizational investment in order to
      enhance optimal APN practice and to benefit patients and families.

PMID- 15714019
TI  - Enhancing presentation skills for the advanced practice nurse: strategies for
      success.
AB  - Professional speaking is a component of the professional practice role of the
      advanced practice nurse (APN). The skills to communicate effectively to one
      person or an audience of 100 provide the APN with the essential tools for
      implementing change, collaborating effectively, presenting information at
      professional meetings, or communicating the impact of clinical outcomes in the
      boardroom. Public speaking skills, a professional image, and improved
      communication can facilitate advancement along any career ladder. The greater
      your fear, the more self-confidence you will gain by stepping up to a challenge
      and conquering it. This article describes strategies for organizing and
      presenting your message in a clear and concise format. Techniques to manage the
      anxiety produced when attempting to articulate your thoughts is essential for
      effective communication. Skills for enhancing the delivery of your message
      through effective body language, professional image, voice modulation, and use of
      audiovisual aids are addressed. Creative techniques for fielding questions are
      key in promoting a dynamic closure and provide consistent reinforcement of the
      key message content.

PMID- 15714020
TI  - Program development: role of the clinical nurse specialist in implementing a fast
      track postanesthesia care unit.
AB  - Advanced practice nurses are involved in many aspects of program development as
      part of their roles. This can involve such things as developing programs for
      staff and family education, organizing system-wide quality assurance programs, or
      implementing new care programs. One unique aspect of the advanced practice
      nurse's role is the ability to serve as a change agent and implement new models
      of care. Although all advanced practice nurses can be involved in program
      development, the role of the Clinical Nurse Specialist lends itself to devoting
      dedicated services for implementing programmatic change in the clinical setting.
      This article describes the role of the Clinical Nurse Specialist in implementing
      an evidence-based, fast-track postanesthesia care unit.

PMID- 15714021
TI  - Expanding acute care nurse practitioner and clinical nurse specialist education:
      invasive procedure training and human simulation in critical care.
AB  - Programs educating advanced practice nurses (APNs), including acute care nurse
      practitioners (ACNPs) and clinical nurse specialists (CNSs) may struggle with the
      degree to which technical and cognitive skills necessary and unique to the care
      of critically ill patients should be incorporated within training programs, and
      the best ways these skills can be synthesized and retained for clinical practice.
      This article describes the critical care technical skills training mechanisms and
      use of a High-Fidelity Human Simulation (HFHS) Laboratory in the ACNP and CNS
      programs at the University of Pittsburgh School of Nursing. The mechanisms for
      teaching invasive procedures are reviewed including an abbreviated course
      syllabus and documentation tools. The use of HFHS is discussed as a measure to
      provide students with technical and cognitive preparation to manage critical
      incidents. The HFHS Laboratory, scenario development and implementation, and the
      debriefing process are discussed. Critical care technical skills training and the
      use of simulation in the curriculum have had a favorable response from students
      and preceptors at the University of Pittsburgh School of Nursing, and have
      enhanced faculty's ability to prepare APNs.

PMID- 15714028
TI  - Identifying primary and secondary skin lesions.

PMID- 15714030
TI  - Nutrients for wound healing.

PMID- 15714031
TI  - Preventing heel pressure ulcers in immobilized patients.

PMID- 15714032
TI  - New year payment system changes for hospital-owned outpatient wound departments.

PMID- 15714033
TI  - Coming to consensus on deep tissue injury.

PMID- 15714034
TI  - What is causing a persistent skin boil?

PMID- 15714035
TI  - Hydration: an essential nutrient.

PMID- 15714036
TI  - Pressure-related deep tissue injury under intact skin and the current pressure
      ulcer staging systems.
AB  - OBJECTIVE: To identify how current pressure ulcer staging systems and experts
      describe pressure-related deep tissue injury under intact skin in the published
      research literature. DESIGN: A systematic review of published English-language
      literature as of November 2002 with the words decubitus or pressure ulcer(s) in
      the title. Additional relevant articles were identified by National Pressure
      Ulcer Advisory Panel members and were included in the analysis. An expert
      commentary was developed by iterative review by the National Pressure Ulcer
      Advisory Panel members. MAIN OUTCOME MEASURES: Manuscripts were reviewed for
      staging systems cited or described, definitions of Stage I pressure ulcers, and
      descriptions or definitions of pressure-related deep tissue injury under intact
      skin. MAIN RESULTS: Ninety-four relevant articles were identified. Seventy-three
      articles (78%) described a staging system, and 55 of 73 (75%) cited the staging
      definitions from Shea, the National Pressure Ulcer Advisory Panel, or the Agency
      for Health Care Policy and Research. The National Pressure Ulcer Advisory Panel's
      staging definitions were the most frequently cited overall. Twenty-three articles
      (25%) included some discussion that could be interpreted as relevant to the topic
      of pressure-related deep tissue injury under intact skin; however, no consistency
      in definitions of Stage I pressure ulcers or terminology for pressure-related
      deep tissue injury under intact skin was found. CONCLUSIONS: Several pressure
      ulcer staging systems are frequently cited, but none define pressure-related deep
      tissue injury under intact skin. The National Pressure Ulcer Advisory Panel
      recommends using the terms "pressure-related deep tissue injury under intact
      skin" or "deep tissue injury under intact skin" for describing these lesions and
      encourages investigators to establish the epidemiology and natural history of
      these lesions.

PMID- 15714037
TI  - The art of skin and wound care documentation.
AB  - PURPOSE: To provide physicians and nurses with an overview of strategies for
      descriptive documentation of skin and wound assessments and interventions. TARGET
      AUDIENCE: This continuing education activity is intended for physicians and
      nurses with an interest in learning about strategies for documenting skin and
      wound assessments and interventions. OBJECTIVES: After reading the article and
      taking the test, the participant should be able to: 1. Describe documentation
      related to the use of risk assessment and manual assessment tools. 2. Describe
      documentation related to the use of skin and wound assessment tools.

PMID- 15714040
TI  - Alcohol effects on central nervous system gene expression in genetic animal
      models.
AB  - This article summarizes the proceedings of a symposium presented at the 2004
      annual meeting of the Research Society on Alcoholism in Vancouver, British
      Columbia, Canada. The organizers and chairs were William J. McBride and Michael
      F. Miles. The presentations were (1) Molecular Triangulation on Gene Expression
      Patterns in Behavioral Responses to Acute Ethanol, by Robnet T. Kerns; (2) Gene
      Expression in Limbic Regions After Ethanol Self-Infusion Into the Posterior
      Ventral Tegmental Area, by Zachary A. Rodd; (3) Microarray Analysis of CNS Limbic
      Regions of Inbred Alcohol-Preferring and -Nonpreferring rats and Effects of
      Alcohol Drinking, by Wendy N. Strother and Howard J. Edenberg; and (4) Microarray
      Analysis of Mouse Lines Selected for Chronic Ethanol Withdrawal Severity: The
      Convergence of Basal, Ethanol Regulated, and Proximity to Ethanol Quantitative
      Trait Loci to Identify Candidate Genes, by Joel G. Hashimoto and Kristine M.
      Wiren.

PMID- 15714041
TI  - CREB gene transcription factors: role in molecular mechanisms of alcohol and drug
      addiction.
AB  - This article presents the proceedings of a symposium presented at the meeting of
      the Research Society on Alcoholism, held in Vancouver, British Columbia, Canada,
      in June 2004. The organizers and chairpersons were Subhash C. Pandey and Fulton
      Crews. The presentations were (1) Ethanol Modulation of CREB: Role in Dependence
      and Withdrawal, by Fulton Crews; (2) Effects of D1 Dopamine Receptor Activation
      During Withdrawal From Chronic Morphine: Enhanced CREB Activation and Decreased
      Conditioned Place Aversion, by Elena H. Chartoff; (3) CREB-Haplodeficient Mice:
      Role in Anxiety and Alcohol-Drinking Behaviors, by Subhash C. Pandey; and (4) A
      Role for CREB in Stress and Drug Addiction, by Julie A. Blendy.

PMID- 15714043
TI  - Context effects on alcohol cognitions.
AB  - This article summarizes a symposium on context and alcohol-related cognitions
      presented at the 2004 Annual Meeting of the Research Society on Alcoholism in
      Vancouver, British Columbia, Canada. The studies reported here examine how the
      manipulation of contextual variables influences the availability of alcohol
      outcome expectancies and implicit memories for alcohol associations. The
      symposium illustrates the range of context variables and shows some of the
      potential impact of retrieval on cognitions that predict alcohol use. Two of the
      studies explore naturalistic drinking contexts: one examines the impact of stress
      induction, and one assesses within survey question placement effects. A variety
      of measures of alcohol cognitions were used. The results demonstrate that alcohol
      cognitions are more accessible in alcohol-related contexts. Moreover,
      availability of alcohol associations and expectancies depended on individual
      differences. These results underscore the potential value of memory processes in
      the retrieval and measurement of alcohol cognitions. The findings have direct
      implications for improving methods of predicting alcohol use and in understanding
      the role of alcohol cognitions in various contexts associated with alcohol use.

PMID- 15714042
TI  - Stress enhancement of craving during sobriety: a risk for relapse.
AB  - This report of the proceedings of a symposium presented at the 2004 Research
      Society on Alcoholism Meeting provides evidence linking stress during sobriety to
      craving that increases the risk for relapse. The initial presentation by Rajita
      Sinha summarized clinical evidence for the hypothesis that there is an increased
      sensitivity to stress-induced craving in alcoholics. During early abstinence,
      alcoholics who were confronted with stressful circumstances showed increased
      susceptibility for relapse. George Breese presented data demonstrating that
      stress could substitute for repeated withdrawals from chronic ethanol to induce
      anxiety-like behavior. This persistent adaptive change induced by multiple
      withdrawals allowed stress to induce an anxiety-like response that was absent in
      animals that were not previously exposed to chronic ethanol. Subsequently, Amanda
      Roberts reviewed evidence that increased drinking induced by stress was dependent
      on corticotropin-releasing factor (CRF). In addition, rats that were stressed
      during protracted abstinence exhibited anxiety-like behavior that was also
      dependent on CRF. Christopher Dayas indicated that stress increases the
      reinstatement of an alcohol-related cue. Moreover, this effect was enhanced by
      previous alcohol dependence. These interactive effects between stress and alcohol
      related environmental stimuli depended on concurrent activation of endogenous
      opioid and CRF systems. A.D. Le covered information that indicated that stress
      facilitated reinstatement to alcohol responding and summarized the influence of
      multiple deprivations on this interaction. David Overstreet provided evidence
      that restraint stress during repeated alcohol deprivations increases voluntary
      drinking in alcohol-preferring (P) rats that results in withdrawal-induced
      anxiety that is not observed in the absence of stress. Testing of drugs on the
      stress-induced voluntary drinking implicated serotonin and CRF involvement in the
      sensitized response. Collectively, the presentations provided convincing support
      for an involvement of stress in the cause of relapse and continuing alcohol abuse
      and suggested novel pharmacological approaches for treating relapse induced by
      stress.

PMID- 15714044
TI  - Adolescence: booze, brains, and behavior.
AB  - This article represents the proceedings of a symposium at the 2004 Research
      Society on Alcoholism meeting in Vancouver, British Columbia, Canada, organized
      and chaired by Peter M. Monti and Fulton T. Crews. The presentations and
      presenters were (1) Introduction, by Peter M. Monti; (2) Adolescent Binge
      Drinking Causes Life-Long Changes in Brain, by Fulton T. Crews and Kim Nixon; (3)
      Functional Neuroimaging Studies in Human Adolescent Drinkers, by Susan F. Tapert;
      (4) Abnormal Emotional Reactivity as a Risk Factor for Alcoholism, by Robert
      Miranda, Jr.; (5) Alcohol-Induced Memory Impairments, Including Blackouts, and
      the Changing Adolescent Brain, by Aaron M. White and H. Scott Swartzwelder; and
      (6) Discussion, by Kenneth Sher.

PMID- 15714045
TI  - The role of acetaldehyde in the central effects of ethanol.
AB  - This article represents the proceedings of a symposium at the 2004 annual meeting
      of the Research Society on Alcoholism in Vancouver, Canada. The symposium was
      organized by Etienne Quertemont and chaired by Kathleen A. Grant. The
      presentations were (1) Behavioral stimulant effects of intracranial injections of
      ethanol and acetaldehyde in rats, by Merce Correa, Maria N. Arizzi and John D.
      Salamone; (2) Behavioral characterization of acetaldehyde in mice, by Etienne
      Quertemont and Sophie Tambour; (3) Role of brain catalase and central formed
      acetaldehyde in ethanol's behavioral effects, by Carlos M.G. Aragon; (4)
      Contrasting the reinforcing actions of acetaldehyde and ethanol within the
      ventral tegmental area (VTA) of alcohol-preferring (P) rats, by William J.
      McBride, Zachary A. Rodd, Avram Goldstein, Alejandro Zaffaroni and Ting-Kai Li;
      and (5) Acetaldehyde increases dopaminergic transmission in the limbic system, by
      Milena Pisano and Marco Diana.

PMID- 15714046
TI  - Active ingredients: how and why evidence-based alcohol behavioral treatment
      interventions work.
AB  - This article summarizes the proceedings of a symposium that was organized and
      chaired by Richard Longabaugh and presented at the 2004 Research Society on
      Alcoholism meeting in Vancouver, British Columbia, Canada. The aim of the
      presentation was to focus on evidence for the active ingredients of behavioral
      therapies for patients with alcohol use disorders. Dennis M. Donovan, PhD,
      reviewed evidence for the active ingredients of cognitive behavioral therapy.
      Barbara S. McCrady, PhD, presented a conceptual model for mechanisms of change in
      alcohol behavior couples therapy and reviewed evidence for this model. J. Scott
      Tonigan, PhD, presented data testing three hypothesized mechanisms of change in
      twelve-step facilitation treatment. Mitchell P. Karno, PhD, presented therapy
      process data that tested whether matching therapist behaviors to client attribute
      across three therapies affected drinking outcomes. Jon Morgenstern served as
      discussant.

PMID- 15714047
TI  - Safety and efficacy of GABAergic medications for treating alcoholism.
AB  - This article highlights the proceedings of a symposium presented at the 27th
      Annual Scientific Meeting of the Research Society on Alcoholism in Vancouver,
      British Columbia, Canada, June 29, 2004. The organizers and co-chairs were
      Bankole A. Johnson, MD, PhD, and Robert M. Swift, MD, PhD. The presentations
      included (1) Introduction, by Bankole A. Johnson; (2) Safety, Tolerability, and
      Efficacy of gamma-Hydroxybutyric Acid and Baclofen in the Treatment of Alcohol
      Addiction, by Giovanni Addolorato; (3) Safety of Gabapentin in Treating
      Alcoholism, by Hugh Myrick; (4) New Data on the Safety and Effectiveness of
      Topiramate in the Treatment of Alcohol Dependence, by Bankole A. Johnson; (5)
      Evaluating the Risk of Benzodiazepine Prescription to Alcohol-Dependent
      Individuals, by Domenic A. Ciraulo; and (6) Safety and Efficacy of GABAergic
      Agents in Treating Alcoholics: Discussion, by Robert M. Swift.

PMID- 15714048
TI  - Complying with the minimum drinking age: effects of enforcement and training
      interventions.
AB  - This article summarizes the proceedings of a symposium presented at the 2004
      Research Society on Alcoholism meeting in Vancouver, British Columbia, organized
      by Alexander C. Wagenaar and chaired by Mark S. Goldman. The purpose of the
      symposium was to present the design and outcomes from a recently completed multi
      community controlled time-series trial entitled Complying with the Minimum
      Drinking Age (CMDA), which tested two approaches for enhancing the effectiveness
      of the legal drinking age policy: training of alcohol retailers, and police
      enforcement at alcohol establishments. Specific presentations were: (1)
      Introduction and Overview of the CMDA project by Alexander C. Wagenaar, (2) CMDA
      Interventions by Traci L. Toomey, (3) CMDA Measurement, Statistical Methods and
      Results by Darin J. Erickson, and (4) Conclusions, Implications and Future
      Applications by Alexander C. Wagenaar. Results from the trial show: (1) minimal
      effects of the brief version of Alcohol Risk Management training for alcohol
      outlet management, (2) significant effects of enforcement checks in reducing
      sales of alcohol to youth, (3) a concentration of effects in specific alcohol
      outlets experiencing an enforcement check with little diffusion of effects to
      other outlets in the community not experiencing a check, and (4) a substantial
      decay of enforcement effects over the three months following a specific check. In
      short, results showed significant and substantial specific deterrence effects,
      and little training effects. Results also illustrated the utility and strength of
      the controlled time-series trial research design. Additional research on temporal
      and geospatial distribution of community-level intervention effects is warranted.

PMID- 15714049
TI  - Explicating alcohol's role in acquaintance sexual assault: complementary
      perspectives and convergent findings.
AB  - This article summarizes the proceedings of a symposium presented at the 2004
      meeting of the Research Society on Alcoholism (RSA) in Vancouver, British
      Columbia, Canada. There were four presentations and a discussant. The symposium
      was co-chaired by Tina Zawacki and Jeanette Norris. The first presentation was
      made by Jeanette Norris, who found that alcohol consumption and preexisting
      alcohol expectancies affected women's hypothetical responses to a vignette
      depicting acquaintance sexual aggression. The second presentation was made by
      Joel Martell, who reported that alcohol-induced impairment of executive cognitive
      functioning mediated the effect of intoxication on men's perceptions of a sexual
      assault vignette. In the third presentation, Antonia Abbey found that the
      experiences of women whose sexual assault involved intoxication or force were
      more negative than were the experiences of women whose sexual assault involved
      verbal coercion. The fourth presentation was made by Tina Zawacki, who reported
      that men who perpetrated sexual assault only in adolescence differed from men who
      continued perpetration into adulthood in terms of their drinking patterns and
      attitudes toward women. William H. George discussed these findings in terms of
      their implications for theory development and prevention programming.

PMID- 15714050
TI  - Demon rum: high-tech solutions to an age-old problem.
AB  - This article summarizes the proceedings of a symposium at the 2004 Research
      Society on Alcoholism Meeting in Vancouver, British Columbia, Canada, organized
      and chaired by Scott T. Walters. The purpose of the symposium was to describe
      several brief motivational interventions offered via the Internet, including the
      evidence for web-based interventions, applications and contexts in which such
      approaches are being used, and directions for future research. Walters provided
      an overview and introduction to the topic and discussed the e-CHUG (www.e
      chug.com) and e-TOKE (www.e-toke.com) feedback interventions for college alcohol
      and marijuana prevention, including the contexts in which they are being used and
      ways they are being integrated with other campus prevention efforts. Dr. Hester
      presented 12-month results from a controlled trial of the Drinker's Check-up
      (www.drinkerscheckup.com), an intervention for adult problem drinkers that is
      available both as a Windows and as an Internet application. Dr. Chiauzzi
      described the development and testing of My Student Body (www.mystudentbody.com),
      a tailored drinking prevention web site for college students. Finally, Dr. Miller
      addressed the use of online assessment and feedback to reduce drinking, including
      the history of web-based interventions and their likely future and the potential
      limitations of such approaches.

PMID- 15714051
TI  - New developments in prevention and early intervention for alcohol abuse in
      youths.
AB  - This article summarizes a symposium held at the 2004 Annual Meeting of the
      Research Society on Alcoholism in Vancouver, British Columbia, Canada. It was
      prepared by the conference co-organizers/co-chairs with substantial input from
      each of the symposium participants. Increasingly, alcohol abuse interventions
      focus on preventing alcohol problems or intervening early before risky drinking
      behavior becomes ingrained. Universal prevention programs have produced no or
      only modest effects on the drinking behavior of youths. Although some existing
      targeted prevention programs have proved effective, they have not tapped the full
      range of potential intervention targets, such as the underlying motivations for
      alcohol misuse in youths who are at greatest risk. The set of papers presented in
      this symposium outline exciting new developments in the field of targeted
      prevention and early intervention programs for adolescent drinking problems,
      presented by an international panel of researchers. These developments include
      attention to making interventions relevant to adolescents' lives, focus on
      personality and motivational factors underlying alcohol misuse, and combining
      existing cognitive behavioral programs with expectancy challenge and motivational
      interviewing techniques.

PMID- 15714052
TI  - Neuroimaging of rodent and primate models of alcoholism: initial reports from the
      integrative neuroscience initiative on alcoholism.
AB  - Neuroimaging of animal models of alcoholism offers a unique path for
      translational research to the human condition. Animal models permit manipulation
      of variables that are uncontrollable in clinical, human investigation. This
      symposium, which took place at the annual meeting of the Research Society on
      Alcoholism in Vancouver, British Columbia, Canada, on June 29th, 2004, presented
      initial findings based on neuroimaging studies from the two centers of the
      Integrative Neuroscience Initiative on Alcoholism funded by the National
      Institute on Alcohol Abuse and Alcoholism. Effects of alcohol exposure were
      assessed with in vitro glucose metabolic imaging of rat brain, in vitro receptor
      imaging of monkey brain, in vivo magnetic resonance imaging of monkey brain, and
      in vivo magnetic resonance spectroscopic quantification of alcohol metabolism
      kinetics in rat brain.

PMID- 15714057
TI  - Molecular diagnostic techniques for the clinical evaluation of gliomas.
AB  - Newly developed molecular techniques have been integrated into the routine
      assessment of gliomas in some laboratories. These tests serve to complement the
      subjective nature of morphologic analysis. Such strategies add useful information
      regarding pathogenicity, patient survival, and potential response to treatment.
      As we learn more about the molecular characteristics of these tumors, this
      information will provide the basis for the development of specific, targeted
      therapies. This review will describe the background, methods, clinical utility,
      and strengths and weaknesses of several molecular approaches, including
      fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), loss of
      heterozygosity (LOH)-testing, and nucleic acid sequencing, that are currently
      being employed in the diagnosis and evaluation of glial tumors.

PMID- 15714058
TI  - Multiplex ligation-dependent probe amplification for the detection of chromosomal
      gains and losses in formalin-fixed tissue.
AB  - Molecular analysis on formalin-fixed paraffin-embedded tissue is of increasing
      importance in diagnostic histopathology and tumor research. Multiplex ligation
      dependent probe amplification (MLPA) is a technique that can be used for
      detection of copy number alterations of up to 45 different DNA sequences in one
      experiment. It can be performed on partially degraded DNA, which makes this
      technique very suitable for analysis of formalin-fixed lesions. We tested the
      reliability of MLPA by analyzing DNA isolated from formalin-fixed melanomas that
      were previously characterized by comparative genomic hybridization (CGH), and
      additionally the applicability of MLPA was tested by analyzing 29 routinely
      processed melanocytic lesions. MLPA appears to be a reliable and efficient method
      to evaluate DNA copy number changes as 86% of the loci tested revealed concordant
      CGH results. Discordance mainly involved alterations that were detected by MLPA
      and not by CGH probably due to a combination of lower resolution of CGH and
      occasionally false positive MLPA results. For application of MLPA in a diagnostic
      setting, different probes on a specific region of interest should be used to
      prevent false positive MLPA results. In a research setting as well as in a
      diagnostic setting, MLPA is a fast technique to screen large numbers of formalin
      fixed lesions for DNA gains and losses.

PMID- 15714059
TI  - Detection of BCL2-IGH using single-round PCR assays.
AB  - The translocation t(14;18) resulting in fusion of the BCL2 and the immunoglobulin
      heavy chain genes (BCL2-IGH) is present in 80% to 90% of follicular lymphomas and
      20% to 30% of diffuse large B-cell lymphomas. Polymerase chain reaction (PCR)
      analysis for the translocation products suffers from low analytic specificity. As
      a result, either nested PCR or probe hybridization is required to aid in the
      identification of the specific translocation products. These added procedures are
      undesirable in clinical laboratories because nested procedures increase the
      possibility of contamination and probe hybridization increases assay turnaround
      time. To simplify the BCL2-IGH assay procedure, we attempted to eliminate the
      nonspecific PCR products by optimizing the annealing temperatures of the PCR
      assays using a gradient thermocycler. We showed that gradually increasing the
      annealing temperature from 55 degrees C to 67 degrees C significantly enhanced
      the intensity of the specific PCR products while eliminating the nonspecific
      ones. We compared the simplified procedure with a PCR-probe hybridization method
      on 68 patient specimens. The simplified procedure had increased analytic and
      diagnostic specificities with comparable sensitivities. With significantly
      improved analytic specificity, one round of PCR is sufficient to detect the BCL2
      IGH gene rearrangements without further confirmation.

PMID- 15714060
TI  - Molecular diagnosis of Ewing's sarcoma/primitive neuroectodermal tumor in
      formalin-fixed paraffin-embedded tissues by RT-PCR and fluorescence in situ
      hybridization.
AB  - Recent studies have suggested that formalin-fixed paraffin-embedded (FFPE)
      tissues can be used for molecular analyses by fluorescence in situ hybridization
      (FISH) and RT-PCR. We analyzed 18 cases of ES/PNET for the t(11;22)(q24;q12) and
      t(21;22)(q22;q12) fusion transcripts by RT-PCR and analyzed for EWS translocation
      by interphase FISH with a dual color fusion probe to compare these two approaches
      directly. RT-PCR detected 13 (72%) EWS-FLI-1 fusions (type I=10, type II=3) and 2
      (11%) EWS-ERG fusions. Three cases could not be evaluated because the
      housekeeping gene phosphoglycerate kinase (internal mRNA control) was not
      amplified. FISH was diagnostic in 15 of 18 cases (83%). There were three
      discordant cases between RT-PCR and FISH (concordance of 83%). Using a
      combination of RT-PCR and FISH, the results were complementary. One advantage of
      RT-PCR analysis was that subtypes of EWS translocation could be determined
      specifically (type I, type II and ERG). These findings indicate that because of
      the difficulties and limitations associated with the molecular analysis of FFPE
      tissues, a combination of RT-PCR and FISH may be a better approach to enhance the
      sensitivity and accuracy of detecting ES/PNET translocations in FFPE tissues with
      suboptimally preserved nucleic acids.

PMID- 15714061
TI  - Real-time PCR measures Epstein-Barr Virus DNA in archival breast adenocarcinomas.
AB  - The role of Epstein-Barr Virus (EBV) in breast cancer pathogenesis remains
      controversial. Fifty-five cases of paraffin-embedded, formalin-fixed invasive
      breast cancer were screened for the presence of EBV using quantitative polymerase
      chain reaction (PCR) directed at five different targets within the EBV genome
      (BamH1W, LMP1, EBNA1, LMP2, and BZLF1 regions). In four tumors (7%), low level
      EBV DNA was detected by at least one of the assays, with levels of up to 11
      copies of EBV DNA per 100,000 cells. Immunohistochemisty for viral BMRF1 and
      BZLF1 and in situ hybridization for lytic gene transcripts showed no evidence of
      replicative EBV gene expression. Lymphocytes and malignant cells were also
      negative for latent infection by EBER in situ hybridization. Laser capture
      microdissection followed by quantitative real-time PCR was not useful in
      localizing EBV DNA to malignant cells or bystander lymphocytes. In conclusion,
      EBV DNA is detectable in a fraction of breast cancer specimens using real-time
      PCR as a screening tool, albeit at quite low levels, which suggests that only
      rare cells are infected. The low levels probably confounded our ability to
      localize the virus to particular cell types or to characterize viral gene
      expression.

PMID- 15714062
TI  - Genomic allelotyping for distinction of recurrent and de novo hepatocellular
      carcinoma after orthotopic liver transplantation.
AB  - Distinction between recurrent and de novo hepatocellular carcinoma (HCC) after
      orthotopic liver transplantation (OLT) bears important clinical and therapeutic
      implications. Techniques for molecular profiling of clinically suspected de novo
      and recurrent HCC are required since the histological/clinical discrimination of
      donor vs. recipient tumor origin is difficult. Multiple PCR amplification of 16
      highly polymorphic short tandem repeat (STR) DNA sequences (routinely used for
      paternity and forensic assays) was applied in two patients who developed a second
      HCC after OLT. In both patients the technique provided reliable evidence that the
      two second HCC were recurrences of the primary tumor. Multiple STR genetic
      allelotyping is an effective tool for clear-cut discrimination of donor/recipient
      origin of a second HCC after OLT. Its application could be of great therapeutic
      relevance for such OLT patients.

PMID- 15714063
TI  - Distribution of immune cell subsets and cytokine-producing cells in the uterine
      cervix of human papillomavirus (HPV)-infected women: influence of HIV-1
      coinfection.
AB  - The aim of this study was to characterize the immune system profile in the
      uterine cervix of 17 human papillomavirus (HPV)-infected women, compared with 17
      whom were coinfected with HIV-1. Five histologically normal cervices in
      immunocompetent women were used as controls. HPV infection was associated with a
      marked increase in cells expressing interleukin (IL)-6, interferon gamma (IFN
      gamma), and tumor necrosis factor alpha (TNF-alpha). Coinfection by HPV and HIV-1
      led to decreased expression of IL-6, TNF-alpha, and IFN-gamma. However,
      coinfection led to increased numbers of cells expressing IL-4, IL-10, and IL-8.
      Compared with the histologically normal cervices, increased numbers of
      macrophages (CD68, RFD7) and T lymphocytes (CD4, CD8) were seen in HPV-infected
      cervices; coinfection with HIV-1 was associated with a higher number of CD8 cells
      and lower number of CD68 cells. HPV DNA localized exclusively to the dysplastic
      squamous cells, whereas HIV-1 RNA was detected mainly in CD68-positive stromal
      cells. In conclusion, this study shows differential expression of various
      cytokines and classes of inflammatory cells, relative to HIV-1 infection and HPV
      coinfection, which may relate to the risk of transmission of HIV-1 and increased
      risk of cervical cancer in these women.

PMID- 15714064
TI  - Correlation of HIV-1 detection and histology in AIDS-associated emphysema.
AB  - HIV-seropositive individuals are at an increased risk for an accelerated form of
      emphysema. The purpose of this study was to determine the distribution of HIV-1
      RNA in lung tissues and correlate this with the histologic findings and
      expression of matrix metalloproteases (MMPs). Reverse transcriptase (RT) in situ
      PCR analysis was performed on 11 AIDS lung autopsy specimens which showed varying
      degrees of emphysematous changes. In each lung, HIV-1 RNA was detected. In areas
      of histologically normal lung, very rare HIV-1-infected cells were evident. In
      contrast, many HIV-1-infected cells were noted in areas of emphysema. HIV-1 gag
      RNA was evident primarily in macrophages; infected pneumocytes were also seen.
      Similarly, MMP mRNA and protein, primarily MMP-9, localized to the areas of
      emphysema. Colabeling experiments documented that MMP expression was found
      primarily in cells that were HIV-1 negative and adjacent to HIV-1-infected
      macrophages. These results suggest that AIDS-related emphysema may be due, in
      part, to direct infection by HIV-1 of, primarily, alveolar macrophages, and
      concomitant up-regulation of MMP expression in the neighboring, noninfected
      cells.

PMID- 15714065
TI  - The doublecortin gene, a new molecular marker to detect minimal residual disease
      in neuroblastoma.
AB  - Neuroblastoma (NB) is a pediatric cancer of highly variable clinical outcome.
      Much effort is devoted to detection of minimal residual (MRD) disease through RT
      PCR or immunology of tissue-specific markers. Tyrosine hyrdroxylase (TH) has
      demonstrated a high utility to assess disease dissemination, although this marker
      can be lost due to clonal variability. Here we propose the use of the
      doublecortin (DCX) gene as a new molecular marker of neuroblastoma cells. DCX
      specifically appears in migrating neurons of the central and peripheral nervous
      system and interacts with and regulates the microtobule cytoskeleton. We have
      studied this gene by real-time quantitative RT-PCR in a total of 47 primary
      tumors and 202 samples of bone marrow or peripheral blood from 34 high-risk
      neuroblastoma patients as well as in 41 normal controls. The expression of DCX
      demonstrated a good specificity and concordance with TH, showing a higher
      expression rate in all the sample types studied as well as at different time
      points from diagnosis. We conclude that DCX would be a more efficient marker of
      minimal disease in neuroblastoma and perhaps other tumors of neuronal lineage.

PMID- 15714066
TI  - Chronic obstructive pulmonary disease in women.
AB  - Chronic obstructive pulmonary disease is a chronic, progressive, debilitating
      disease caused primarily by smoking. This article will present a case study of a
      female with chronic obstructive pulmonary disease with emphasis on the physical
      examination, laboratory data, and healthcare management.

PMID- 15714068
TI  - Aortic aneurysm in pregnancy: a case study.
AB  - This is an interesting case study about a patient in her 37th week of pregnancy
      who develops an aortic aneurysm. The pathophysiology and medical and nursing care
      of these patients are discussed.

PMID- 15714069
TI  - The stress response, psychoneuroimmunology, and stress among ICU patients.
AB  - Multiple stressors, physical and psychological, may beset intensive care unit
      patients. This article opens with a description of the stress cascade and its
      connection with immunity. Examples of intensive care unit stressors follow, along
      with various proposed interventions to reduce psychological stress among
      intensive care unit patients. Although researchers have yet to establish that
      such interventions will positively impact immune function, they are an essential
      component of compassionate and holistic care.

PMID- 15714070
TI  - Essential qualities of an effective clinical leader.
AB  - Strong and effective clinical leadership is needed by practicing nurses as our
      healthcare systems continue to decentralize and shift decision making closer to
      the bedside. Innovation and new ways of leading and following are required. New
      forms of clinical leadership can energize and transform today's work
      environments.

PMID- 15714071
TI  - Innovative solutions: developing computer-based instruction for the nursing unit
      computers.
AB  - This short article describes one hospital's efforts to develop a computer-based
      instruction program for critical care nurses who care for patients undergoing
      increased intracranial pressure monitoring.

PMID- 15714072
TI  - Innovative solutions: a collaborative effort of critical care oncology: the
      common ground of tubes and lines.
AB  - The intensive care units and the oncology units at Banner Good Samaritan Medical
      Center are for complex patients who require multiple and diverse venous access
      devices. The critical care clinical nurse specialist and the oncology/bone marrow
      transplant clinical nurse specialist collaborated to create a reference sheet for
      nurses regarding the care and maintenance of venous/arterial access devices.

PMID- 15714073
TI  - Comparison of characteristics of heart failure by race and gender.
AB  - Heart failure (HF) affects almost 4.8 million Americans, occurring in men and
      women of all races. Half of those with HF are women; of the African American
      population, almost 3% are affected by HF. Although recent HF research has focused
      on women and minorities, information is still needed regarding differences by
      race and gender. The purpose of this study was to compare risk factors and
      physiologic differences by race (African American and Caucasian) and gender that
      exist in those with HF.

PMID- 15714074
TI  - Critical care visitation.

PMID- 15714075
TI  - How frequent is altered gene expression among susceptibility genes to human
      complex disorders?
AB  - It is regularly thought that human complex disorder susceptibility genes show
      differences in gene expression between normal and pathologic tissues. Thus,
      differences of transcript amounts could be indicative of complex disorder
      susceptibility loci and, therefore, be used for the discovery or the validation
      of human susceptibility genes to complex disorders/traits. Whether human complex
      disorder susceptibility genes effectively display differences in transcript
      amounts was tested by meta-analysis of the published literature comparing
      transcript amounts of well-validated human susceptibility genes to complex
      traits/disorders. A total of 94 gene-disease associations, which were studied in
      at least three independent studies and showed strong evidence of positive
      association, were analyzed. For 23 out of these 94 well-validated gene-disease
      associations, 120 gene expression studies comparing normal and pathologic human
      tissues were found. For 60 out of these 120 gene expression studies, the
      difference of level expression between normal and pathologic human tissues was
      statistically significant. This result was highly significant, as only 6
      significant results were expected randomly under the null hypothesis (P < 10(
      112)). A large excess of replication studies were also found, which were in
      agreement with the original report (P = 6 x 10(-4)). However, the overall level
      of expression change between normal and pathologic human tissues was relatively
      moderate, because only 36 (60%) and 19 (31.6%) out of the 62 statistically
      significant gene expression studies reached 2- or 3-fold changes in expression
      level, respectively. The present meta-analysis confirms statistical differences
      of expression levels between normal and pathologic human tissues for human
      susceptibility genes to complex traits/disorders. However, the levels of
      differences in transcript amounts appear to be relatively weak. These findings
      rationalize the use of gene expression for the discovery/validation of human
      susceptibility genes, but the weak differences of expression typically found
      should be taken into account for the design of such studies.

PMID- 15714076
TI  - CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients:
      a HuGEnet systematic review and meta-analysis.
AB  - PURPOSE: Two common variant alleles of the cytochrome CYP2C9 (CYP2C9*2 and
      CYP2C9*3) lead to reduced warfarin metabolism in vitro and in vivo. The study
      objective was to examine the strength and quality of existing evidence about
      CYP2C9 gene variants and clinical outcomes in warfarin-treated patients. METHODS:
      The study was a systematic review and meta-analysis. Multiple electronic
      databases were searched, references identified from bibliographies were sought,
      and experts and authors of primary studies were also contacted. Strict review
      inclusion criteria were determined. Three reviewers independently extracted data
      using prepiloted proformas. RESULTS: In all, 11 studies meeting review inclusion
      criteria were identified (3029 patients). Nine were included in the meta-analyses
      (2775 patients). Random effects meta-analyses were performed; statistical
      heterogeneity and inconsistency was assessed. Twenty percent of patients studied
      carry a variant allele: CYP2C9*2 12.2% (9.7%-15.0%) and CYP2C9*3, 7.9% (6.5%
      9.7%). Mean difference in daily warfarin dose: for CYP2C9*2, the reduction was
      0.85 mg (0.60-1.11 mg), a 17% reduction. For CYP2C9*3, the reduction was 1.92 mg
      (1.37-2.47 mg), a 37% reduction. For CYP2C9*2 or *3, the reduction was 1.47 mg
      (1.24-1.71 mg), a 27% reduction. The relative bleeding risk for CYP2C9*2 was 1.91
      (1.16-3.17) and for CYP2C9*3 1.77 (1.07-2.91). For either variant, the relative
      risk was 2.26 (1.36-3.75). CONCLUSIONS: Patients with CYP2C9*2 and CYP2C9*3
      alleles have lower mean daily warfarin doses and a greater risk of bleeding.
      Testing for gene variants could potentially alter clinical management in patients
      commencing warfarin. Evidence for the clinical utility and cost-effectiveness of
      genotyping is needed before routine testing can be recommended.

PMID- 15714077
TI  - Individualization of long-term enzyme replacement therapy for Gaucher disease.
AB  - Gaucher disease, the most common lysosomal storage disorder, is a heterogeneous
      condition affecting multiple organ systems. Patients with nonneuronopathic (type
      1) Gaucher disease may suffer from hepatomegaly, splenomegaly, thrombocytopenia,
      bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth
      retardation, pulmonary disease, and decreased quality of life. Enzyme replacement
      therapy (ERT) with mannose-terminated glucocerebrosidase (imiglucerase, Cerezyme,
      Genzyme Corporation, Cambridge, MA) reverses or ameliorates many of the
      manifestations of type 1 Gaucher disease. However, due to the variable pattern
      and severity of disease, and the uncertain manner of progression, implementation
      of treatment, choice of initial and maintenance imiglucerase dose, and evaluation
      of the therapeutic response must be tailored to the individual patient. For the
      past 14 years, the US Regional Coordinators of the International Collaborative
      Gaucher Group have individually and collectively developed extensive clinical
      experience in managing patients with Gaucher disease. In this review, we present
      recommendations for initial imiglucerase treatment and subsequent dose
      adjustments based on a schedule of regular assessment and monitoring, and
      achievement and maintenance of defined therapeutic goals.

PMID- 15714078
TI  - Application of ROMA (representational oligonucleotide microarray analysis) to
      patients with cytogenetic rearrangements.
AB  - PURPOSE: To demonstrate the accuracy and sensitivity of Representational
      Oligonucleotide Microarray Analysis (ROMA) to describe copy number changes in
      patients with chromosomal abnormalities. METHODS: ROMA was performed using BglII
      digested DNA from two cases with cytogenetically detected deletions and one case
      with an unbalanced terminal rearrangement detected only by subtelomeric FISH.
      Hybridization was to an 85,000-probe oligonucleotide microarray, providing an
      average resolution of 35 kb. FISH was used to confirm some of the ROMA findings.
      RESULTS: By ROMA, a del(13)(q14.3q21.2) was shown to be noncontiguous, with
      deletions extending from 53.08 to 61.40 Mb and from 72.88 to 74.83 Mb. The 10-Mb
      deletion contained only six known genes. FISH confirmed the noncontiguous nature
      of the deletion, as well as a small amplification in 6q that was also found in
      the patient's mother. A del(4)(q12q21.2) was found by ROMA to be 23 Mb in length,
      from 58.8 to 81.9 Mb on chromosome 4, in agreement with the cytogenetically
      assigned breakpoints. ROMA showed that an unbalanced "subtelomeric" rearrangement
      involved a 6-Mb deletion of 22q and an 8-Mb duplication of 16q. CONCLUSIONS: ROMA
      can define cytogenetic aberrations with extraordinary precision. Unexpected
      findings included the interrupted nature of the deletion in 13q and the large
      size of the imbalances in the "subtelomeric" rearrangement. Together with the
      information from the human genome sequence and proteomics, the ability to define
      rearrangements with "ultra-high" resolution will improve the ability to provide
      accurate prognosis both prenatally and postnatally to parents of offspring with
      chromosomal aberrations.

PMID- 15714079
TI  - Late-onset Tay-Sachs disease: phenotypic characterization and genotypic
      correlations in 21 affected patients.
AB  - PURPOSE: The purpose of this study was to describe the phenotype (and
      corresponding genotype) of adult patients with late-onset Tay-Sachs disease, a
      clinical variant of the GM2-gangliosidoses. METHODS: A comprehensive physical
      examination, including neurological assessments, was performed to establish the
      current disease pattern and severity. In addition, the patients' past medical
      histories were reviewed. The patients' alpha-subunit mutations (beta
      Hexosaminidase A genotype) were determined and correlated with their
      corresponding clinical findings and disease course. RESULTS: Twenty-one patients
      (current mean age: 27.0 years; range: 14-47 years) were identified. The pedigree
      revealed a relative with the "classic" infantile or late-onset form of Tay-Sachs
      disease in four (out of 18) unrelated families. The patients were predominantly
      male (15/21 individuals) and of Ashkenazi Jewish ancestry (15/18 families). Mean
      age at onset was 18.1 years; balance problems and difficulty climbing stairs were
      the most frequent presenting complaints. In several cases, the diagnosis was
      delayed (mean age at diagnosis: 27.0 years). Analysis of the beta-hex A gene
      revealed the G269S mutation as the most common disease allele; found in
      homozygosity (N = 1) or heterozygosity (N = 18; including 2 sib pairs). Disease
      onset (age 36 years) was delayed and progression relatively slower in the
      homozygous G269S patient. Two siblings (ages 28 and 31 years), of non-Jewish
      ancestry, were compound heterozygotes (TATC1278/W474C); their clinical course is
      dominated by psychiatric problems. Brain imaging studies revealed marked
      cerebellar atrophy in all patients (N = 18) tested, regardless of disease stage.
      CONCLUSIONS: Late-onset Tay-Sachs disease is an infrequent disorder and the
      diagnosis is often missed or delayed (by approximately 8 years). Early on, the
      majority of patients develop signs of either cerebellar or anterior motor neuron
      involvement. Affected individuals may also develop psychotic episodes. In most
      cases, the later-onset of expression results from the presence of at least one
      allele (usually the G269S mutation), associated with residual enzyme (beta
      hexosaminidase A) activity. A positive family history is a valuable clue,
      enabling early diagnosis. Nonspecific cerebellar atrophy on brain imaging is
      another important finding. This entity should be considered among patients
      presenting with speech, gait, and balance problems, and those with psychiatric
      disorders even when focal neurologic deficits may be initially absent. Accurate
      diagnosis will permit appropriate genetic counseling regarding disease prognosis
      and reproductive risks.

PMID- 15714080
TI  - Computerized cognitive testing in patients with type I Gaucher disease: effects
      of enzyme replacement and substrate reduction.
AB  - PURPOSE: Because of concern for drug-induced cognitive dysfunction during
      clinical trials using substrate reduction therapy (miglustat) in type 1 Gaucher
      disease and because it has been suggested that some patients with type 1 Gaucher
      disease may develop neurocognitive impairment as part of the natural history, two
      different batteries of neuropsychological tests were devised to examine these
      issues. Using these tests, cognitive function was assessed in patients treated
      with miglustat, in patients receiving enzyme replacement (standard care for
      symptomatic patients), and in untreated (milder) patients. METHODS: For this
      study, 55/60 patients exposed to miglustat in Israel participated in psychologist
      administered testing; 36/55 participated in computerized testing. Of these, 31
      enzyme-treated patients and 22 untreated patients participated in the
      psychologist-administered testing, and 15 enzyme-treated patients and 18
      untreated patients participated in computerized testing. The psychologist
      administered battery consisted of 18 standard neuropsychological subtests
      specific to executive and visuospatial functioning. The computerized battery
      (Mindstreams, NeuroTrax Corp., New York, NY) consisted of 10 subtests tapping
      multiple cognitive domains. Between-group analyses for each modality compared
      cognitive performance. RESULTS: In the psychologist-administered testing,
      patients exposed to miglustat performed significantly less well than the other
      groups in 5/18 subtests. On the computerized tests, all patients performed
      comparably to normal controls. Scores in patients exposed to miglustat were
      higher than in untreated patients, particularly in visuospatial function, whereas
      enzyme-treated patients performed less well. However, with the exception of
      visuospatial function, these results were not statistically significant.
      CONCLUSIONS: It is unclear why different testing methods yielded discordant
      results. Any dysfunction suggested by the current study is apparently subtle and
      of doubtful clinical relevance given that cognitive status did not interfere with
      patients' daily intellectual function. The computerized battery has
      methodological advantages (e.g., language options, objectivity, brevity, and ease
      of use) that make it well-suited for longitudinal studies, for long-term
      surveillance of substrate reduction therapy as well as for comparisons with other
      lysosomal storage disorders and other chronic diseases. These preliminary
      findings should allay fears of cognitive dysfunction due to short-term miglustat
      therapy.

PMID- 15714081
TI  - Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic
      laboratory.
AB  - PURPOSE: Based on results of diagnostic MEN1 testing, we have attempted to
      further define the mutational spectrum of the MEN1 gene and the clinical features
      most frequently associated with MEN1 mutations. METHODS: Mutation testing was
      performed on blood samples by PCR amplification and sequencing of exons 2 to 10
      of the MEN1 gene and the corresponding intron-exon junctions. Pedigree phenotypic
      information was obtained by written questionnaire. RESULTS: Among 288 presumably
      unrelated pedigrees, 73 independent mutations were found in 89 families. Five
      mutations were found in 2 pedigrees, and 4 mutations were seen in more than 2
      pedigrees. There were 17 nonsense mutations (23.3%), 2 in-frame deletions (2.7%),
      18 frameshift-deletion mutations (24.7%), 10 frameshift-insertion or -duplication
      mutations (13.7%), 13 splice-site mutations (17.8%), and 13 presumptive missense
      mutations (17.8%). Thirty-nine of 56 pedigrees with parathyroid and pancreatic
      islet neoplasia tested positive, compared with 4/24 and 8/32 pedigrees affected
      with hyperparathyroidism or hyperparathyroidism and pituitary tumors. MEN1
      mutations were found in 6/20 sporadic patients, all of whom had both parathyroid
      and pancreatic neoplasms. Of 14 mutation-negative sporadic patients, 10 exhibited
      hyperparathyroidism and pituitary tumors without islet cell neoplasia. Somatic
      mosaicism was detected in 1 sporadic patient. CONCLUSION: Patients from pedigrees
      with hyperparathyroidism and pancreatic islet tumors are most likely to test
      positive for MEN1 mutations. Mutations are less often detected in patients from
      pedigrees with hyperparathyroidism alone or in combination with pituitary tumors
      without pancreatic islet neoplasia. Sporadic cases are less likely to test
      positive than familial cases, in part due to somatic mosaicism.

PMID- 15714082
TI  - Systematic follow-up and case management of the abnormal newborn screen can
      improve acceptance of genetic counseling for sickle cell or other
      hemoglobinopathy trait.
AB  - PURPOSE: Sickle cell or other hemoglobinopathy trait detected on the newborn
      screen provides an opportunity for genetic counseling of families at risk of
      having a child with a major hemoglobinopathy. However, follow-up of
      hemoglobinopathy trait is often fragmented and acceptance of counseling is low.
      We describe the results of systematic follow-up and case management of abnormal
      newborn screen and the effect on acceptance of counseling. METHODS: From July
      1997 to June 2002, families of a newborn with hemoglobinopathy trait were
      notified by mail. In April 2003, an intensive trait follow-up protocol including
      letters, telephone calls, educational videos, and genetic counseling was
      implemented. Demographic information and follow-up activity were documented and
      tracked using an electronic database. RESULTS: From July 1997 to June 2002, 3095
      families were notified by letter of a newborn with hemoglobinopathy trait and
      were offered genetic counseling. Of these, 165 (5.3%) received counseling by
      telephone and 60 (2%) underwent extended family testing. From April to December
      2003, 694 families with a newborn with hemoglobinopathy trait were notified by
      mail. Of these, 362 (52%) families were reached by telephone. Of those contacted
      by telephone, 92% received genetic counseling via telephone, 57% were interested
      in family testing, and 12% scheduled an appointment. Additionally, 27% of
      families were mailed an educational video. Among those declining extended family
      testing, 26% preferred to consult their pediatrician. CONCLUSIONS: Systematic
      follow-up and case management of abnormal newborn screen can improve the
      acceptance of genetic counseling.

PMID- 15714083
TI  - Safety and efficacy of enzyme replacement therapy in combination with
      hematopoietic stem cell transplantation in Hurler syndrome.
AB  - PURPOSE: Hurler syndrome is a debilitating genetic disease with a typical life
      span of 5 to 8 years. Early hematopoietic stem cell transplantation (HSCT)
      mitigates disease symptoms and improves survival. However, morbidity and
      mortality associated with HSCT can limit its success. We describe the initial
      experience with combined use of enzyme replacement therapy (ERT, laronidase) and
      HSCT in Hurler syndrome. METHODS: Thirteen transplants were performed in 12
      patients. ERT was given at a standard dose of 0.58 mg/kg per week. Transplant
      conditioning regimen and donor graft source were determined by institutional
      protocol. RESULTS: The median age at initiation of ERT was 12 months (range, 8 to
      18 months). The median duration of pre-HSCT ERT was 12 weeks (range, 4 to 28).
      All but 1 patient tested showed decrease in urinary GAG excretion during ERT. ERT
      infusion-related toxicity was limited to mild reactions. Development of
      antibodies to laronidase did not correlate with infusion reactions or responses
      in urinary GAG excretion. ERT was given for a median of 7 weeks (range, 3 to 20)
      after HSCT. After transplantation, eight patients demonstrated complete donor
      engraftment and four suffered graft failure. Two patients required ventilator
      support and three developed acute GVHD. Eleven of the 12 patients are surviving
      with a median follow-up of 3 months (range, 1 to 7 months). CONCLUSIONS: In
      children with Hurler syndrome, ERT with HSCT is feasible and well tolerated.
      Development of antibodies against exogenous enzyme does not appear to correlate
      with infusion reactions or response to ERT. A prospective study is needed to
      determine the effect of concomitant ERT on transplant outcomes.

PMID- 15714084
TI  - Infantile onset Pompe disease: a report of physician narratives from an
      epidemiologic study.
AB  - PURPOSE: To review the narratives that detailed the most important features of
      Infantile Onset Pompe disease (IOPD) from the physician's perspective, submitted
      as part of a large multicenter, multinational epidemiologic natural history
      study. METHODS: Inclusion in the epidemiologic study required documentation of
      onset of symptoms in the first 12 months of age and GAA enzyme deficiency or GAA
      mutation(s). In all, 300 cases were screened; 168 cases from 33 study sites in 9
      countries met all eligibility criteria. In addition, 125 narratives that
      summarized the most important clinical features of IOPD, reflecting the opinion
      of the participating physicians who had provided access to the records for the
      independent review, were analyzed and are reported separately. A total of 98
      variables were analyzed. RESULTS: Hypotonia was the most common presenting
      symptom, occurring in 75% of patients; muscle weakness was a presenting symptom
      in 59% of patients. The most frequent sign noted on physical examination was
      hypotonia (82%); respiratory distress, cardiomegaly, weakness, and cardiac
      failure were also frequent. Progression of disease was characterized by increased
      respiratory distress (72%), hypotonia (66%), and cardiac failure (58%). The most
      frequent supportive treatments were cardiac medications (52%) and oxygen
      supplementation (35%). Little psychosocial information was included. CONCLUSION:
      Physician narratives provide a unique perspective on the natural history of IOPD
      and are useful adjuncts to other data collection. Overall, there was concordance
      with the data obtained by the independent abstractors.

PMID- 15714086
TI  - Manganese-calcium interactions with contrast media for cardiac magnetic resonance
      imaging: a study of manganese chloride supplemented with calcium gluconate in
      isolated Guinea pig hearts.
AB  - OBJECTIVES: Manganese ions (Mn) enter cardiomyocytes via calcium (Ca) channels
      and enhance relaxation intracellularly. To prevent negative inotropy, new Mn
      releasing contrast agents have been supplemented with high Ca. The study aim was
      to investigate how this affects cardiac function and magnetic resonance efficacy.
      MATERIALS AND METHODS: MnCl2 based contrast agents, manganese and manganese
      calcium (Ca:Mn 10:1), were infused during 4 repeated washin-washout sequences in
      perfused guinea pig hearts. [Mn] were 10, 50, 100 and 500 microM. RESULTS: During
      washin, manganese depressed left ventricular developed pressure (LVDP) by 4, 9,
      17, and 53% whereas manganese-calcium increased LVDP by 13, 18, 25, and 56%.
      After experiments, tissue Mn contents (nmol/g dry wt) were control <40, manganese
      3720, and manganese-calcium 1620. T1 was reduced by 85-92% in Mn-enriched hearts.
      CONCLUSIONS: High Ca supplements to Mn-releasing contrast agents may be
      counterproductive by inducing a strong positive inotropic response and by
      reducing the magnetic resonance efficacy.

PMID- 15714087
TI  - Multislice computed tomography-urography: intraindividual comparison of different
      preparation techniques for optimized depiction of the upper urinary tract in an
      animal model.
AB  - OBJECTIVES: We sought to evaluate intraindividually 3 different preparation
      protocols for achieving improved opacification and anatomic depiction of the
      upper urinary tract in multisclice computed tomography urography (MSCTU) using a
      porcine model. MATERIAL AND METHODS: MSCTU was performed in 8 healthy pigs. Each
      animal underwent 3 MSCT urographies using 3 different preparations before the
      injection of contrast material: A, intravenous (iv) saline (250 mL); B, iv low
      dose furosemide (0.1 mg/kg); and C, iv saline (250 mL) plus iv low-dose
      furosemide (0.1 mg/kg). Image analysis was performed blinded to the applied
      protocols and included the evaluation of the opacification and anatomic depiction
      of the upper urinary tract by means of graded scales. Ureteral distension was
      determined and density was measured within the collecting system. RESULTS:
      Furosemide significantly improved both mean opacification scores and mean scores
      of anatomic depiction compared with the exclusive infusion of saline for MSCTU.
      There was no significant difference between the application of furosemide and the
      combination of furosemide plus saline. A significant increase of 25-26% for
      ureteral distension was found when furosemide was applied. Significant lower mean
      attenuation values (Hounsfield units) and standard deviation were found within
      the opacified urine for diuretic-enhanced MSCTU. CONCLUSIONS: Low-dose furosemide
      injection is superior to saline infusion for achieving optimal enhancement in
      MSCTU. It is not necessary to combine furosemide and saline infusion. In MSCTU,
      low-dose furosemide is a simple add-on simplifying image acquisition timing and
      removing the need for abdominal compression devices.

PMID- 15714088
TI  - Contrast-enhanced computed tomography and ultrasound for the evaluation of tumor
      blood flow.
AB  - OBJECTIVE: We evaluated implanted rat mammary adenocarcinoma tumors during a 5
      week period using ultrasound, computed tomography (CT), and histology. MATERIALS
      AND METHODS: Contrast-enhanced ultrasound with a destruction-replenishment
      imaging scheme was used to derive estimates of blood volume and flow. These
      ultrasound-derived measures of microvascular physiology were compared with
      contrast-enhanced CT-derived measures of perfusion and vascular volume made by
      the Mullani-Gould formula and Patlak analysis, respectively. RESULTS: The tumor
      cross-sectional area and necrotic core cross-sectional area determined by the 3
      methods were correlated (r>0.8, P<0.001, n=15). The spatial integral of perfusion
      estimated by CT correlated with the spatial integral of flow from ultrasound
      (P<0.05). The contrast-enhanced tumor area calculated from the ultrasound
      analysis was highly correlated with the contrast-enhanced area estimated by CT
      images (r=0.89, P<0.001, n=15). However, the fraction of the tumor area enhanced
      by the CT contrast agent was significantly larger than either the fraction
      enhanced by ultrasound contrast agent or than the viable area as estimated from
      histology slides. CONCLUSION: Destruction-replenishment ultrasound provides
      valuable information about the spatial distribution of blood flow and vascular
      volume in tumors and ultrasound analysis compares favorably with a validated
      contrast-enhanced CT method.

PMID- 15714089
TI  - Coronary calcium scoring using 16-row multislice computed tomography: nonenhanced
      versus contrast-enhanced studies in vitro and in vivo.
AB  - OBJECTIVES: We sought to assess the agreement of coronary artery calcium score in
      nonenhanced and contrast-enhanced multislice-spiral computed tomography.
      MATERIALS AND METHODS: Vessel phantoms and 36 patients underwent nonenhanced and
      contrast-enhanced cardiac multislice-spiral computed tomography (Sensation 16;
      Siemens, Germany). Reconstruction-parameters: slice thickness 3 mm, increment 2
      mm, kernels B35f and B30f. The Agatston score, calcium mass, and number of
      lesions were calculated. Images were scored using detection thresholds of 130
      Hounsfield units (HU) and 350 HU. Based on the Agatston score, risk
      stratification was performed. RESULTS: In the phantom and patient study, altering
      the threshold from 130 to 350 HU led to a significant decrease in the mean
      Agatston score (phantom: 54.6%, patients: 66.7%) and calcium mass (33.0%, 47.0%)
      (B35f). Contrast-enhanced studies (threshold: 350 HU) showed an increase of the
      mean Agatston score (71.0%, 20.7%) and calcium mass (81.0%, 16.0%) when compared
      with nonenhanced scans (threshold: 350 HU). A total of 57% of all patients were
      assigned to different risk groups. CONCLUSIONS: Contrast material may simulate
      calcification; therefore, calculation of the coronary calcium score from contrast
      enhanced images is not reliable.

PMID- 15714090
TI  - The importance of end-systole for optimal reconstruction protocol of coronary
      angiography with 16-slice multidetector computed tomography.
AB  - OBJECTIVES: Multidetector-row computed tomography coronary images are usually
      analyzed in mid-diastole (MD). Because of slow coronary motion also in end
      systole (ES), we evaluated the impact on image quality of including ES images and
      defined an efficient reconstruction protocol. MATERIAL AND METHODS: In 50
      coronary multidetector-row computed tomography studies, 9 reconstructions (at 10%
      increments of the RR interval) were graded for image quality. Multiple
      combinations of reconstructions were compared. RESULTS: MD (60-70% of the RR
      interval) offered the best image quality. In 44% patients, the best
      reconstruction for >or=1 coronary was found in ES (20-30%). Their heart rate was
      higher (68.2+/-9.9 bpm vs. 59.2+/-8.8 bpm, P=0.0014). Combining ES and MD
      consistently offered superior image quality and less nonevaluable vessels than
      even larger numbers of diastolic reconstructions alone. A combination of 2-3
      reconstructions was most efficient. Adding more reconstructions did not
      significantly improve results. CONCLUSIONS: Combining ES and MD reconstructions
      reduces nonevaluable coronary arteries, particularly with higher heart rates. A
      protocol including 2-3 reconstructions is the most efficient.

PMID- 15714091
TI  - Magnetic resonance imaging gastrography: evaluation of the dark lumen technique
      compared with conventional gastroscopy in patients with malignant gastric
      disease.
AB  - OBJECTIVES: We sought to demonstrate the feasibility of depicting gastric tumors
      using magnetic resonance imaging (MRI) while applying the dark lumen technique.
      The findings were correlated with conventional gastroscopy. In addition, we
      evaluated the screening for lymph nodes and liver metastases during the same
      session to identify potential tumor spread. MATERIALS AND METHODS: The study
      included 15 patients with known malignant gastric disease. Conventional
      gastrointestinal endoscopy was performed in all patients as gold standard. All
      patients were examined with computed tomography for tumor staging. MRI was
      performed using 1 L of tap water as oral contrast agent for all protocols. The
      MRI program included an axial T1-weighted (T1w; 2D-FLASH) sequence, an axial STIR
      and T2w (TSE) sequence, and 2 postcontrast T1w (3D coronal /2D axial FLASH)
      sequences using 0.2 mmol/kg gadolinium diethylenetriaminepenta-acetic acid as
      intravenously injected contrast agent. Qualitative analysis and comparison with
      conventional gastroscopy were performed. RESULTS: The images obtained with the
      postcontrast 3D coronal T1w-FLASH sequence were the most suitable in identifying
      gastric tumors. Complete correlation with conventional gastroscopy was achieved
      in 80% of the cases and partial correlation in 13% of the cases. The same imaging
      sequence was also appropriate for the evaluation of lymph nodes. For the
      identification of liver metastases, the images obtained with the axial
      postcontrast T1w 2D-FLASH sequence provided a higher diagnostic confidence as
      compared with other imaging protocols. CONCLUSIONS: Applying the dark lumen
      technique through MRI is suitable for imaging gastric tumors and has the
      potential to become a "one-stop shopping" method because of the possibility for
      lymph node evaluation and screening for metastases during the same session based
      on the same images.

PMID- 15714092
TI  - Evaluation of lung volumetry using dynamic three-dimensional magnetic resonance
      imaging.
AB  - RATIONALE AND OBJECTIVES: We sought to investigate lung volume and surface
      measurements during the breathing cycle using dynamic three-dimensional magnetic
      resonance imaging (3D MRI). MATERIALS AND METHODS: Breathing cycles of 20 healthy
      volunteers were examined using a 2D trueFISP sequence (3 images/second) in
      combination with a model and segmented 3D FLASH sequence (1 image/second) MR
      images using view sharing. Segmentation was performed semiautomatically using an
      interactive region growing technique. Vital capacity (VC) was calculated from MRI
      using the model (2D) and counting the voxels (3D) and was compared with
      spirometry. RESULTS: VC from spirometry was 4.9+/-0.9 L, 4.4+/-1.2 L from 2D MRI
      measurement, and 4.7+/-0.9 L for 3D MRI. Using the 3D technique, correlation to
      spirometry was higher than using the 2D technique (r>0.95 vs. r>0.83). Using the
      3D technique, split lung volumes and lung surface could be calculated. There was
      a significant difference between the left and right lung volume in expiration
      (P<0.05). CONCLUSIONS: Dynamic 3D MRI is a noninvasive tool to evaluate split
      lung volumes and lung surfaces during the breathing cycle with a high correlation
      to spirometry.

PMID- 15714093
TI  - Soft-copy reading of digital chest radiographs: effect of ambient light and
      automatic optimization of monitor luminance.
AB  - OBJECTIVE: We sought to evaluate whether soft-copy reading of simulated pulmonary
      chest lesions is influenced by ambient light and automatic optimization of
      cathode ray tube (CRT) monitor luminance. MATERIALS AND METHODS: Four types of
      simulated lesions (nodules, lines, micronodules, and patchy opacities) were
      superimposed over an anthropomorphic chest phantom. Lesion detection with soft
      copy reading was assessed using a high-contrast grayscale 2K CRT monitor under
      the following conditions: (1) subdued lighting (<50 lux); (2) normal lighting
      conditions (450 lux) without, and (3) with a sensitivity modulation to
      automatically adjust the CRT luminance to the increased amount of ambient light.
      Reading data were analyzed according to receiver operating curve. Significance of
      differences was tested using an analysis of variance for repeated measures.
      RESULTS: Ambient room light of 450 lux did not significantly influence the
      detection of nodules and patchy opacities. However, bright ambient light
      significantly decreased detection of micronodules (0.60 vs. 0.74) and lines (0.52
      vs. 0.66) relative to subdued lighting conditions. Automatic luminance adjustment
      could compensate the effect of ambient light for the micronodules (0.77) but not
      for the lines (0.53). CONCLUSION: Bright ambient light significantly decreases
      detection of small low-contrast structures. This may be partially but not
      completely compensated by an automatic luminance adaptation.

PMID- 15714094
TI  - Technological system solutions to clinical communication error.

PMID- 15714095
TI  - Bridging the strategic leadership gap: a model program for transformational
      change.
AB  - The University of Pittsburgh Medical Center (UPMC) recognized the impending
      crisis--a vast nurse leader shortage, especially at the strategic level. UPMC's
      new development model establishes a dependable leadership pipeline. The model
      identifies high-potential individuals, verifies required competencies, assesses
      participants' strengths, and provides a didactic and experiential learning
      curriculum. Within 2 years, the program produced a 450% return on investment and
      evolved into the Health Care Leadership Academy, an open enrollment program for
      emerging, operational, and strategic leaders nationwide.

PMID- 15714096
TI  - Advanced practice nursing: leadership to effect policy change.
AB  - Nursing leaders used evidence-based thinking to engage key stakeholders when
      implementing advanced practice nursing roles in a traditional medically oriented
      tertiary oncology center. A strategic orientation to the policy change initiative
      was guided by a theoretical framework for connecting research and policy. Policy
      approaches that addressed stakeholder values and beliefs, while attending to
      questions of competence, standards of practice, fiscal savings, medical and
      nursing workload, and ongoing multidisciplinary teamwork were essential to
      facilitate change.

PMID- 15714097
TI  - A model for evaluating systemic change: measuring outcomes of hospital discharge
      education redesign.
AB  - Hospitals have restructured job duties and responsibilities in response to market
      pressures and in an effort to improve quality. This study presents a model for
      evaluating patient satisfaction outcomes following a work redesign that included
      the realignment of responsibility for discharge education from clinical nurse
      specialists to cross-trained, multidisciplinary workers. The outcomes data cannot
      be generalized, as they relate to a particular redesign and one institution.
      However, this analysis provides a framework for a systematic, multidisciplinary
      approach to evaluating organizational change.

PMID- 15714099
TI  - Nontraditional models of care delivery: have they solved the problems?
AB  - Healthcare delivery systems in the United States are changing rapidly in response
      to socioeconomic forces. In the new competitive healthcare market, work has been
      redesigned, with hospitals changing their skill mix to include unlicensed
      assisitive personnel. Having previously described the more traditional models of
      care delivery, (JONA, June 2004), the authors will now discuss a variety of
      nontraditional practice models that have been developed to address the changing
      needs of healthcare. These models and their driving forces are described.
      Indicators of success, including quality, cost, and satisfaction, are also
      examined.

PMID- 15714100
TI  - Active error management: use of a Web-based reporting system to support patient
      safety initiatives.
AB  - The authors examine the implementation of a Web-based reporting system in a rural
      academic medical center to support patient safety initiatives. Discussion centers
      on how an online support system can support active error management and help
      identify latent errors. This strategy can help administrators in their efforts to
      develop and institute improvements to prevent subsequent errors. By making
      changes in clinical process and refinement in policies and procedures,
      administrators can uncover trends and patterns across settings.

PMID- 15714101
TI  - Using organizational mission, vision, and values to guide professional practice
      model development and measurement of nurse performance.
AB  - An organization's mission, vision, and values statements are the guiding forces
      behind the institution's administrative strategic planning and performance
      assessment activities. Linking nursing professional practice model components and
      performance evaluation criteria with each of these foundational documents assures
      that their values, beliefs, and intentions are evident in daily work life.

PMID- 15714102
TI  - A process improvement project: achieving quality outcomes.
AB  - The University of Virginia Health System designed a systematic approach to the
      care of the long-term, mechanically ventilated, adult patient population to
      improve patient outcomes and use institutional resources more efficiently. The
      authors discuss their process improvement strategies, barriers to implementation,
      and project outcomes.

PMID- 15714104
TI  - Coronary computed tomography in coronary risk assessment.

PMID- 15714105
TI  - Depression screening in cardiac rehabilitation: AACVPR Task Force Report.

PMID- 15714106
TI  - Maintenance of exercise capacity and physical activity patterns 2 years after
      cardiac rehabilitation.
AB  - BACKGROUND: The benefits of exercise training for postmyocardial infarction and
      postcoronary artery bypass surgery patients are well established, but little is
      known about the effects of rehabilitation in the months or years following the
      program. The purpose of this study was to assess exercise capacity, blood lipids,
      and physical activity patterns 2 years after completing a concentrated
      residential rehabilitation program in Switzerland. METHODS: Seventy-eight
      patients (86% males, mean age = 56 +/- 10, mean ejection fraction = 64% +/- 12%)
      were referred to a residential rehabilitation program after a myocardial
      infarction or coronary artery bypass surgery between January 2001 and June 2001.
      Patients lived at the center for 1 month, during which time they underwent
      educational sessions, consumed a low-fat diet, and exercised 2 hours daily. Two
      years after completing the program, patients returned to the hospital and
      underwent a maximal exercise test, an assessment of recent and adulthood physical
      activity patterns, and evaluation of blood lipids. RESULTS: During the 2-year
      follow-up period, there were 5 deaths, and 70 of the remaining 73 patients
      returned for repeat testing. Mean exercise capacity increased 27% during the
      rehabilitation program (P < .01). Gains in exercise capacity during
      rehabilitation were maintained after the follow-up period; mean exercise capacity
      after 2 years was 34% higher compared with that at baseline (P < .01). At the 2
      year evaluation, patients were expending a mean of 3127 +/- 1689 kcals/wk during
      recreational activities compared with 977 +/- 842 kcals/wk during adulthood prior
      to their cardiac event (P < .001). Between the completion of rehabilitation and
      the 2-year follow-up, total cholesterol, total cholesterol/high-density
      lipoprotein ratio, and triglycerides increased significantly. CONCLUSIONS: Two
      years after a cardiac event and participation in a concentrated residential
      rehabilitation program, patients maintained their exercise capacity and engaged
      in physical activities that exceed the levels recommended by guidelines for
      cardiovascular health. These observations suggest that a relatively intensive
      rehabilitation program provided a catalyst to maintain physical activity patterns
      and exercise tolerance in the 2 years following a cardiac event.

PMID- 15714108
TI  - Patient preferences for home-based versus hospital-based cardiac rehabilitation.

PMID- 15714109
TI  - Is home-based cardiac rehabilitation a preferred and viable option?

PMID- 15714110
TI  - Knowledge of heart attack symptoms in older men and women at risk for acute
      myocardial infarction.
AB  - PURPOSE: Coronary heart disease is the number one cause of death for both men and
      women. While adults 65 years of age and older comprise the largest percentage of
      those who experience an acute myocardial infarction (AMI), investigators to date
      have failed to examine the knowledge of this population about AMI symptoms. The
      purpose of this study was to document knowledge about cardiovascular disease and
      AMI symptoms in older individuals with coronary heart disease to identify the
      characteristics associated with increased knowledge of cardiovascular disease.
      METHODS: A descriptive design was used with a convenience sample of (N = 115)
      older adults at risk for AMI. Data were collected during face-to-face interviews
      in the participants' homes and analyzed using frequencies, percentages, chi, and
      multiple regression analysis. RESULTS: Men and women were not significantly
      different in their knowledge of AMI symptoms except for jaw pain. More than 95%
      of the both men and women knew typical symptoms of AMI, such as chest pain,
      pressure, shortness of breath, arm or shoulder pain, and sweating. Less than 75%
      of both men and women knew that symptoms such as neck pain, nausea or vomiting,
      back pain, heartburn, and jaw pain could be symptoms of AMI. Thirty-one percent
      did not know about reperfusion therapies in the treatment of AMI. Having a
      cardiologist involved in care was weakly predictive of less knowledge.
      CONCLUSIONS: Education and counseling of older patients at high risk for heart
      disease is complex, but should emphasize atypical symptoms and treatment options.

PMID- 15714111
TI  - Warning signs for heart attack and stroke: what more can we do?

PMID- 15714112
TI  - The contribution of peripheral muscle function to shuttle walking performance in
      patients with chronic obstructive pulmonary disease.
AB  - PURPOSE: The contribution of muscle strength and mass to incremental and
      endurance walking performance in chronic obstructive pulmonary disease (COPD) is
      unknown. This study analyzes the relationship between field incremental and
      endurance walking performance and indices of peripheral muscle mass and strength.
      METHODS: Eighty-five stable COPD patients (53 males; mean [SD] age = 67 [9]
      years; mean [SD] forced expiratory volume in 1 second [FEV1] = 35 [14] [%
      predicted]) were studied prior to participation in pulmonary rehabilitation.
      Isometric quadriceps and handgrip strength were measured. Total body and lower
      limb lean muscle mass were estimated using dual energy x-ray absorptiometry.
      Exercise performance was measured using the incremental shuttle walk test (ISWT)
      and the endurance (ESWT) shuttle walk test. RESULTS: ISWT was related to muscle
      strength (r = 0.467, P </= .001) but not to whole body or lower limb lean mass.
      There was no association between muscle strength or mass and ESWT. In a
      multivariate linear regression analysis, the only variables significantly
      contributing to ISWT were age (P < .001), FEV1 (% predicted) (P < .001) and
      quadriceps strength (P < .001). Variables contributing to ESWT were FEV1 (%
      predicted) (P < .001) and ISWT performance (P < .001). CONCLUSIONS: We conclude
      that muscle strength is related to incremental but not endurance shuttle walking
      performance. Muscle mass and strength are not synonymous in their effects on
      exercise performance in patients with COPD.

PMID- 15714113
TI  - Feasibility of distractive auditory stimuli on upper extremity training in
      persons with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the feasibility of distractive auditory stimuli (DAS)
      used during an upper extremity training (UET) program on perceived dyspnea,
      functional performance, and health-related quality of life. In addition, to
      determine the appropriate music tempo used during the UET. DESIGN: Experimental,
      randomized, 3-group design with testing at baseline and 4 weeks. SETTING:
      Outpatient. PATIENTS: Thirty patients (13 male and 17 female) with moderate to
      severe chronic obstructive pulmonary disease (FEV1 41.27% +/- 18% predicted).
      INTERVENTION: Moderate DAS group (n = 10) and slow DAS group (n = 10) subjects
      were instructed to perform UET for up to 15 minutes 3 to 5 times a week using DAS
      (walkman, audiocassettes). The control group (n = 10) received the same
      instructions, but no DAS. MEASURES AND RESULTS: Primary outcome measures were
      perceived dyspnea, functional performance using the 6-minute peg and ring board
      (6MRPB) count and health-related quality of life. In addition, all subjects
      recorded the time of UET performance using self-report (daily logs). A
      significant increase was seen in 6MRPB count (P = .002) between groups. Moderate
      DAS subjects increased 6MPRB count 46 +/- 21 rings and slow DAS subjects
      increased 46 +/- 20 rings from baseline to 4 weeks whereas control subjects
      increased only 5 +/- 4 rings. No significant differences were noted for the
      remaining variables. CONCLUSION: Subjects who used DAS (music) while performing
      UET improved functional performance whereas controls failed to continue
      improvement. The DAS is a feasible adjunct to UET that may have the potential to
      augment the effectiveness of pulmonary rehabilitation training.

PMID- 15714114
TI  - Sunscreen ingredients inhibit inducible nitric oxide synthase (iNOS): a possible
      biochemical explanation for the sunscreen melanoma controversy.
AB  - Sunscreen products are rated upon their ability to inhibit visible redness of the
      skin 24 h after measured doses of ultraviolet (UV) exposure (Sun Protection
      Factor, SPF). Although sunscreens prevent UV-induced redness, their ability to
      protect against melanoma or the development of moles is less clear. UV-induced
      redness occurs in part by the action of nitric oxide (NO), synthesized in the
      skin. NO is also an important immunoregulatory molecule in the induction of the
      cell-mediated tumour immune response. In this study, various sunscreen
      ingredients were tested for their ability to inhibit the production of NO. Four
      of the five sunscreens tested directly inhibited the conversion of arginine to
      citrulline by inducible nitric oxide synthase (iNOS) in vitro. These findings
      suggest that sunscreens may prevent redness partly by UV absorption and partly by
      inhibition of the skin's inflammatory response. As such, sunscreens might promote
      instead of protect against melanoma.

PMID- 15714115
TI  - Wavelength-specific effects on UVB-induced apoptosis in melanocytes. A study of
      Bcl-2/Bax expression and keratinocyte rescue effects.
AB  - Apoptosis and alterations in Bcl-2 and Bax messenger RNA (mRNA) and protein
      expression were examined in cultured human epidermal melanocytes following UVB
      irradiation (50 mJ/cm). The effects of various spectral ranges within UVB were
      investigated. A co-culture system was set up to study the interplay between
      melanocytes and keratinocytes in response to UVB. Melanocytes expressed high
      basal levels of the anti-apoptotic protein Bcl-2 compared with keratinocytes.
      Different wavelengths within the UVB spectrum induced diverse response patterns
      of Bcl-2 and Bax mRNA and had different apoptotic power. Both Bcl-2 and Bax mRNA
      were upregulated to preserve protein levels and only a slight increase in
      apoptosis was noted 24 h after UVB (lambda>305 nm). Increasing UVB between 280
      and 305 nm enhanced apoptosis and upregulated Bcl-2, whilst Bax mRNA was
      unaltered. However, no change in protein levels was detected. A redistribution of
      Bax protein from different compartments within the cell may be more important
      than direct upregulation for the acceleration of apoptosis, but it cannot be
      excluded that other apoptotic pathways may be induced by shorter UVB wavelengths.
      The increase in apoptosis was significantly lower in melanocytes co-cultured with
      irradiated matched keratinocytes than in melanocytes from pure cultures,
      indicating that melanocytes are protected from UVB-induced apoptosis by the
      release of substance(s) from keratinocytes. This rescue response concurred with a
      fast and significant increase in Bcl-2 mRNA level in melanocytes.

PMID- 15714116
TI  - Silencing of the thrombomodulin gene in human malignant melanoma.
AB  - The loss of thrombomodulin (TM) expression is associated with tumour growth,
      infiltration and lymph node metastasis in human tumours. In melanoma cell lines,
      TM is reported to mediate cell adhesion, and its introduction into TM-negative
      melanoma cell lines suppresses their growth. In this study, we analysed TM
      expression in surgical melanoma specimens and the role of its promoter
      methylation in the loss of its expression. In 15 (75%) of the 20 specimens (five
      from a primary site and 15 from metastatic sites), melanoma cells lacked TM
      immunoreactivity. Methylation of the TM promoter region was detected in 10 (67%)
      of the 15 TM-negative specimens by methylation-specific polymerase chain
      reaction, whereas methylation was detected in two (40%) of the five TM-positive
      specimens. In cell lines, complete methylation of the TM promoter CpG island was
      detected in six (46%) of 13 melanoma cell lines, whereas no methylation was
      detected in two cultured normal melanocytes. There was a good correlation between
      the methylated status of the CpG island and the loss of TM messenger RNA (mRNA)
      expression. Treatment of melanoma cell lines with a demethylating agent, 5-aza-2'
      deoxycytidine, induced demethylation of the promoter CpG island and the
      restoration of mRNA and protein expression. These findings suggest that most
      human melanomas lack TM expression, and that methylation of the promoter CpG
      island is one of the mechanisms responsible.

PMID- 15714117
TI  - ErbB receptors mediate both migratory and proliferative activities in human
      melanocytes and melanoma cells.
AB  - Epidermal growth factor receptor (EGFR) activation by transforming growth factor
      alpha (TGFalpha) has been implicated in autocrine growth in melanoma, but does
      not alter melanocyte proliferation. This raises the possibility that different
      signalling pathways are activated via EGFR or ErbB receptors. Here, we
      demonstrate that ErbB2, ErbB3 and ErbB4 are expressed in cultured human
      melanocytes. Western analyses with receptor-specific antisera revealed protein
      bands with Mr values of 185 and 160 kDa, corresponding to ErbB2 and ErbB3,
      respectively. Blots probed with ErbB4 antibodies showed bands with Mr values of
      180, 120 and 80 kDa, corresponding to the receptor and its reported variants. Two
      malignant melanoma cell lines expressed ErbB2 and ErbB3, but not the full-length
      ErbB4 receptor. As TGFalpha binds to EGFR and the heregulins (HRG) bind to ErbB3
      and ErbB4, these growth factors were examined for effects on receptor activation
      and on cell growth and motility in a scratch wound closure assay. In normal
      melanocytes, HRGbeta1 activated the phosphorylation of tyrosine residues of
      proteins that immunoprecipitated with EGFR and ErbB4 antisera, and significantly
      enhanced cell migration but not proliferation. Neither TGFalpha nor HRGalpha1
      promoted migration or growth in normal melanocytes. By contrast, TGFalpha
      stimulated migratory activity in the MM96L cell line, but not in the MELJG line,
      whereas HRGbeta1 significantly enhanced cell growth, but not migration, in both
      malignant cell lines. The apparent transition of HRGbeta1 from a migratory to a
      proliferative function after malignant transformation, and the change in TGFalpha
      from a non-migratory to a migratory activity in one melanoma line, suggests
      multiple switches in ErbB signalling pathways via EGFR/ErbB heterodimer
      formation.

PMID- 15714118
TI  - Efficacy of five human melanocytic cell lines in experimental rabbit choroidal
      melanoma.
AB  - This study was undertaken to compare the ability of five uveal melanocytic cell
      lines to produce primary and metastatic uveal melanomas in immunosuppressed
      rabbits and to determine whether animal survival was improved by antibiotic
      administration. One hundred albino rabbit eyes, five groups of 20, were implanted
      in the suprachoroidal space with four melanoma cell lines (MKT-BR, OCM-1, 92-1
      and SP 6.5) and one melanocytic line (UW-1). Rabbits were immunosuppressed with
      cyclosporin A (CsA) at a dosage of 15 mg/kg/day, decreased to 10 mg/kg/day after
      the fourth week. Prophylactic penicillin G, 10 to 2 x 10 IU, was administered
      intramuscularly at 5-day intervals. Animals were followed for 12 weeks and the
      ophthalmoscopic findings, weight and general well-being were recorded weekly.
      Autopsies were performed to study the eyes, liver and lungs under light
      microscopy. The mean global survival time in the groups was 43+/-4 days.
      Ophthalmoscopic intraocular tumours developed in 37% of the MKT-BR group, 50% of
      the OCM-1 group, 100% of the 92-1 group, 23% of the UW-1 group and 75% of the SP
      6.5 group; histologically, tumours appeared in 36.8%, 45%, 100%, 58.8% and 100%,
      respectively. The 92-1 and SP 6.5 cell lines were associated with the most
      aggressive local behaviour. Lung metastases developed in the OCM-1 group (5%), 92
      1 group (61.1%), UW-1 group (7.1%) and SP 6.5 group (42.1%), but were not present
      in the MKT-BR group. The 92-1 and SP 6.5 cell lines were the most efficient in
      local and metastatic tumour production. Prophylactic antibiotic administration
      did not improve animal survival.

PMID- 15714119
TI  - VEGF and VEGFR-2 immunohistochemistry in human melanocytic naevi and cutaneous
      melanomas.
AB  - Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor
      receptor-2 (VEGFR-2) play a key role in vasculogenesis and angiogenic sprouting,
      which are crucial for tumour development and metastasis. In order to determine
      their possible role in the acquisition of metastatic potential throughout
      melanocytic tumour progression, VEGF and VEGFR-2 immunohistochemical expression
      were evaluated in 36 human melanocytic tumours of the skin (24 malignant
      melanomas and 12 common naevi). Different VEGFR-2 immunostaining patterns were
      detected in the vast majority of melanomas (21/24; 88%). A nuclear membrane-like
      pattern was mainly associated with in situ and microinvasive melanomas, whereas a
      combined cytoplasmic membrane and nuclear membrane-like pattern was seen in
      invasive melanomas. A nuclear membrane-like pattern was also observed in 83%
      (10/12) of common naevi. Cytoplasmic immunostaining for VEGF was observed in 72%
      (8/11) of in situ/microinvasive melanomas, 84% (11/13) of invasive melanomas and
      91% (11/12) of naevi. CD31 was also investigated as an immunohistochemical marker
      for microvessel density (MVD) evaluation. No associations were found between MVD
      and VEGF/VEGFR-2 expression. Taken together, these data indicate that VEGF
      production is a common event in benign melanocytic tumours, whereas VEGFR-2
      expression, co-localized in the cytoplasmic and nuclear membrane, is associated
      with progression towards invasive melanoma. The role exerted by VEGF/VEGFR-2,
      however, seems to be independent of the development of a tumour-related capillary
      network.

PMID- 15714120
TI  - Treatment of metastatic melanoma using electroporation therapy with bleomycin
      (electrochemotherapy).
AB  - Electroporation therapy (EPT) is a novel treatment modality that uses brief, high
      intensity, pulsed electrical currents to enhance the uptake of chemotherapeutic
      agents, vaccines and genes into cells. This technique is potentially useful for
      patients with secondary and, possibly, some primary tumours. Nineteen patients
      with metastatic melanoma were enrolled in a phase two, randomized, open-label
      study comparing intralesional bleomycin+EPT with intralesional bleomycin alone.
      Of 18 study lesions, 13 (72%) showed a complete response, one (5%) showed a
      partial response, three (18%) showed no change and one (5%) showed disease
      progression over a period of greater than 12 weeks. This represents a 78%
      objective response rate, which was significantly greater than the 32% response
      rate observed in the 19 patients with tumours treated with intralesional
      bleomycin alone (chi=7.94, 1 df, P=0.005). An additional 36 lesions, not enrolled
      in the study, were also treated with bleomycin+EPT. Of the total of 54 lesions
      treated with bleomycin+EPT, there was a 72% objective response rate. EPT
      treatment was well tolerated and was performed on an outpatient basis.

PMID- 15714121
TI  - Influence of interleukin-10 genetic polymorphism on survival rates in melanoma
      patients with advanced disease.
AB  - Individual ability to produce interleukin-10 (IL-10) may be of relevance in the
      development and evolution of cutaneous melanoma, probably due to its
      immunosuppressor and anti-angiogenic properties. Single nucleotide polymorphisms
      at positions -1082 (G/A), -819 (C/T) and -592 (C/A) in the IL-10 gene promoter
      were analysed in 100 healthy individuals and 98 melanoma patients using
      fluorogenic hybridization-specific probes in a 'real-time' thermocycler.
      Polymorphic frequencies were correlated with various prognostic factors and
      overall survival. The frequency of IL-10 polymorphic variants was similar in
      patients and controls. However, high producer genotypes at the -1082 position
      were over-represented in males with an older age at diagnosis. The analysis of
      the promoter genotypes in patients stratified according to clinical prognostic
      factors did not show any associations, although a trend (not statistically
      significant) towards a prolonged survival in patients genotyped as high IL-10
      producers was observed. In addition, the low producer -1082AA genotype was
      significantly associated with decreased survival in patients with advanced
      disease. Similarly, the presence of this genotype shortened the overall survival
      in males after recurrence or metastasis development. In conclusion, the frequency
      of genetic variants in the IL-10 gene promoter was not associated with melanoma
      appearance, but conditioned the age at diagnosis in males and the overall
      survival in patients with advanced disease.

PMID- 15714122
TI  - The association between large congenital melanocytic naevi and cutaneous
      melanoma: preliminary findings from an Internet-based registry of 379 patients.
AB  - There is ample evidence in the literature to support the fact that there is an
      increased risk of the development of melanoma in individuals with a large
      congenital melanocytic naevus (LCMN). The published melanoma risk estimates, by
      and large, do not distinguish between cutaneous and extracutaneous melanomas. It
      is currently not known to what extent each contributes to the overall cited
      melanoma risk estimates. In order to obtain a better understanding of the
      association between LCMN and cutaneous melanoma arising within an LCMN, we report
      the preliminary findings of a cross-sectional study of 379 patients, with a
      median age of 3 years, from the first self-referred, Internet-based registry of
      patients with LCMN. To date, no cutaneous melanoma has been reported; possible
      reasons for this finding are discussed. Further research is required to clarify
      the risk of the development of cutaneous melanoma separate from non-cutaneous
      melanoma and to identify subgroups of patients with LCMN at highest risk for the
      development of melanoma. This information will help to formulate appropriate
      decisions concerning the management of patients with LCMN.

PMID- 15714123
TI  - Seasonal variation in the diagnosis of cutaneous melanoma and non-cutaneous
      malignancies: an Italian population-based study.
AB  - The aim of the present study was to investigate whether or not the diagnosis of
      cutaneous melanoma and non-cutaneous tumours shows seasonal variations. Data from
      the Tuscany Cancer Registry, central Italy, for malignant cutaneous melanomas
      (no. 2062) and non-skin cancers (no. 114,755), diagnosed during 1985-2000, were
      used to evaluate the monthly variation in the number of diagnoses. The chi
      squared test was used to evaluate the heterogeneity in the monthly number of
      cancer diagnoses throughout the year and to compare monthly proportions between
      groups. Poisson multivariate regression was used to estimate the monthly risk of
      cancer diagnosis. Clear monthly variations were evident for both melanoma and non
      cutaneous cancers, but the monthly diagnosis distributions differed.
      Statistically significant peaks in June [relative risk (RR), 1.54] and July (RR,
      1.40) and a lower risk for January (RR, 0.76), in comparison with the mean
      monthly value, were documented for melanoma. Monthly risks were similar for thin
      (< or =1 mm) and thick (>1 mm) melanomas and for males and females. A peak in May
      June and October and significantly lower numbers of cases in August and December
      were detected for all non-skin cancers. The holiday periods may influence the
      seasonality in the diagnosis of melanomas and non-cutaneous cancers. However, the
      monthly fluctuation for melanoma differed from that for non-cutaneous cancers;
      the peak in July suggests an additional effect of summer clothing, with fewer
      clothes worn and more skin visible, on melanoma diagnosis.

PMID- 15714124
TI  - Trends in incidence of various morphologies of malignant melanoma in Vaud and
      Neuchatel, Switzerland.
AB  - The trends in the incidence of various morphological types of cutaneous malignant
      melanoma (CMM) in the Swiss Cancer Registries of Vaud and Neuchatel (total
      population 786,000 in 2000) were analysed over the period 1978-2002. Overall, the
      age-standardized (world) incidence of CMM increased from 5.7/100,000 to
      16.8/100,000 for men (+195%) and from 7.9/100,000 to 18.7/100,000 for women
      (+137%). However, there was no consistent trend for nodular melanoma and other or
      unspecified morphological types, and the upward trends were observed for lentigo
      maligna melanoma (from 0.2/100,000 to 1.5/100,000 for men and from 0.5/100,000 to
      2.1/100 000 for women) and mainly superficial spreading melanoma [from
      2.5/100,000 to 10.2/100,000 for men (+308%) and from 3.3/100,000 to 12.3/100,000
      for women (+273%)]. This has implications for aetiology, as the various
      morphological types of CMM may have different determinants, and for prevention,
      as the rise in superficial spreading melanomas, which are comparatively thin, may
      explain the increased survival rates registered for CMM over the last three
      decades.

PMID- 15714125
TI  - Melanoma of unknown primary: experience at Massachusetts General Hospital and
      Dana-Farber Cancer Institute.
AB  - Melanoma may present metastatically without an identifiable primary lesion. To
      further characterize the epidemiology of melanoma of unknown primary (MUP), we
      report our experience with a cohort of MUP patients. We retrospectively reviewed
      patients seen at the Massachusetts General Hospital (MGH) and the Dana-Farber
      Cancer Institute (DFCI) between 1986 and 1996 with follow-up to 2002. Data were
      analysed using log-rank and proportional hazards analyses, with death from any
      cause as the main outcome measure. Of the 2485 melanoma patients seen, 65 (2.6%)
      had MUP; 41 patients were male [63.1%; 95% confidence interval (CI), 50.2%,
      74.7%]. The median age at diagnosis was 54.1 years (interquartile range, 39.4
      67.1 years). Thirty patients had lymph node metastases, 12 cutaneous or
      subcutaneous metastases and 23 visceral metastases. Of the 62 patients (95.4%)
      with at least some follow-up, there were 42 deaths from any cause. Patients with
      lymph node metastases survived significantly longer than patients with other
      metastases [5-year survival 38.7% (95% CI, 18.1%, 59.1%) vs. 13.9% (95% CI, 4.4%,
      28.6%); P<0.01]. After adjusting for stage and age at diagnosis, there was some
      evidence that men survived longer than women [hazard ratio (HR)=0.55; 95% CI,
      0.28, 1.09]. Survival did not differ amongst patients with different types of non
      lymph node metastases. The 5-year survival rates in this cohort did not differ
      from those of historical controls with known primaries. The demographic and
      survival characteristics of this MUP cohort mirrored those found in previous
      studies. More studies of MUP patients, as well as a standardized definition of
      MUP, may shed light on the pathogenesis and prognosis of MUP.

PMID- 15714126
TI  - Identification of an immune tolerance reaction in response to pretreatment with
      frozen pancreatic tissue in islet cell transplantation in rats.
AB  - OBJECTIVES: Whereas transplantation of insulin-secreting pancreatic islets may
      provide long-term control of glucose metabolism in patients with diabetes
      mellitus, transplant rejection remains a problem. In this study, we tried
      pretreatment with frozen pancreatic tissue in a rat model of islet cell
      transplantation to determine whether induction of immune tolerance is feasible.
      METHODS: Isolated islet cells from Wistar rats were transplanted into the spleen
      of recipient rats that were sensitized and rats that were not sensitized with
      frozen pancreatic tissue. Spleens were analyzed histologically and then examined
      immunohistochemically for expression of insulin, a pancreas-specific gene. With
      the use of cDNA primers for proinsulin, RT-PCR was performed to detect islet
      cells in the spleen. RESULTS: Although islet cells were present in spleens at
      posttransplantation day (PTD) 1, islet cell clusters in recipients without
      pretreatment were markedly destroyed on PTD 14 on histologic examination. In
      contrast, islet cell clusters in recipients sensitized with frozen pancreatic
      tissue appeared similar to those at PTD 1 even at PTD 14. Proinsulin gene
      expression was found to be specific to pancreatic tissue. In recipients
      sensitized with frozen pancreatic tissue, proinsulin gene expression was
      identified in recipient spleens, even at PTD 14, whereas it was undetected in the
      absence of pretreatment. In recipients transplanted with islet cells and treated
      simultaneously with frozen pancreatic tissue, proinsulin gene expression was
      completely eliminated. The immunohistologic study also showed the presence of
      insulin-producing islet cells in the spleens of rats sensitized with frozen
      pancreatic tissue. CONCLUSIONS: Inhibition of the immune reaction in transplant
      rejection may be mediated by pretreatment with frozen donor tissue.

PMID- 15714127
TI  - Differential sensitivity to 2-deoxy-D-glucose between two pancreatic cell lines
      correlates with GLUT-1 expression.
AB  - OBJECTIVES: To determine whether the differential growth inhibition of pancreatic
      tumor cells to the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) correlates with
      uptake, expression of GLUT-1 transporter, and levels of hypoxic-inducible factor
      1alpha. METHODS: Growth inhibition assays with 2-DG, lactic acid analysis,
      Western blots of GLUT-1, and hypoxic-inducible factor-1alpha were correlated with
      each other and with uptake and accumulation of radio-labeled 2-DG in 2 pancreatic
      cell lines. RESULTS: Under normal oxygen tension, we find that the pancreatic
      cell line MIA PaCa2 (1420) is 7 times more sensitive to 2-DG and equally
      sensitive to oxamate, as compared with Panc-1 (1469). Lactate levels in both cell
      types are similarly low, indicating that mitochondria are functioning normally in
      these cells and that they are not solely dependent on glycolysis for survival
      under an aerobic microenvironment. Since oxamate does not use glucose
      transporters for entry into the cell, the equal sensitivity to this drug suggests
      that the selective growth inhibition of 2-DG in these 2 cell types might be
      reflective of differential expression of glucose transporters. Indeed, we find
      that GLUT-1 is more highly expressed in 1420 and that this cell line accumulates
      2-DG twice as much as 1469. Additionally, hypoxic-inducible factor, which is
      known to upregulate the expression of GLUT-1, is found at equally low levels in
      both cell types. Thus, the increased expression of GLUT-1 in 1420 appears to be
      independent of hypoxia-inducible factor. CONCLUSION: Overall, our results suggest
      that certain pancreatic tumors may be inherently sensitive to 2-DG, even under
      normal oxygen tension, due to greater intracellular accumulation of this
      inhibitor. Moreover, if 2-DG shows clinical efficacy, it may be possible to
      predict which pancreatic tumors would be sensitive to this agent based on their
      GLUT-1 expression profile and their increased uptake of 2-fluoro-deoxy-D-glucose
      currently used to image tumors via PET scanning.

PMID- 15714128
TI  - Alterations of the tissue inhibitor of metalloproteinase-3 (TIMP3) gene in
      pancreatic adenocarcinomas.
AB  - OBJECTIVES: Tissue inhibitor of metalloproteinase-3 (TIMP3) antagonizes matrix
      metalloproteinase activity and can suppress tumor growth, angiogenesis, invasion,
      and metastases. In the present study, the involvement of TIMP3 in the
      tumorigenesis of 34 pancreatic adenocarcinomas was evaluated. METHODS:
      Immunohistochemistry, methylation-specific PCR, and RNA expression analysis (RT
      PCR) of TIMP3 were performed in 34 resected and microdissected primary pancreatic
      adenocarcinomas. RESULTS: Immunohistochemistry showed loss or strongly reduced
      protein expression in 17 of 34 pancreatic adenocarcinomas (50%) that corresponded
      to loss of TIMP3-RNA-expression. Promoter hypermethylation was identified in 2 of
      34 tumors (6%). It was tumor specific and corresponded to a loss of TIMP3 protein
      expression. TIMP3 alterations did not correlate with any clinical feature such as
      tumor size or survival. CONCLUSION: TIMP3 seems to play an important role in the
      tumorigenesis of primary pancreatic adenocarcinomas. In contrast to other tumors,
      hypermethylation seems not to be the key mechanism for the inactivation of TIMP3.
      Other methods of gene inactivation need to be identified.

PMID- 15714129
TI  - Polymorphism of the TNF-alpha, HSP70-2, and CD14 genes increases susceptibility
      to severe acute pancreatitis.
AB  - OBJECTIVES: Proinflammatory cytokines and heat shock proteins play fundamental
      roles in the pathogenesis of acute pancreatitis. We studied whether polymorphisms
      of the tumor necrosis factor alpha (TNF-alpha), heat shock protein 70-2 (HSP70
      2), and CD14 genes correlate with the severity of acute pancreatitis. METHODS:
      Patients with acute pancreatitis (n = 77) of mixed etiology were grouped
      according to the severity of the disease on the basis of the Ranson scores.
      Healthy blood donors (n = 71) served as controls. TNF-alpha-308 polymorphism was
      determined by NcoI RFLP, HSP70-2 polymorphism by PstI RFLP, and CD14-159
      polymorphism by melting point analysis. RESULTS: There was a moderate increase in
      the frequency of the TNF1/2 genotype (P = 0.046) among patients with severe acute
      pancreatitis as compared with those with mild disease. A more significant
      increase was observed in the frequency of the HSP70-2 G allele between groups of
      patients with mild or severe pancreatitis (18.9% vs. 53%; P < 0.001). Conversely,
      the A/A genotype was markedly more frequent among the patients with mild
      pancreatitis (P < 0.0001). There was no significant correlation between CD14-159
      promoter polymorphism and the severity of pancreatitis. CONCLUSION: High
      frequencies of the HSP70-2 G and the TNF-alpha -308 A alleles were associated
      with risk of severe acute pancreatitis. Genotype assessments may be important
      prognostic tools to predict disease severity and the course of acute
      pancreatitis. Therefore, genotype assessments may also be used to guide treatment
      or to identify risk populations for severe acute pancreatitis.

PMID- 15714130
TI  - Inactive aldehyde dehydrogenase-2 increased the risk of pancreatic cancer among
      smokers in a Japanese male population.
AB  - OBJECTIVES: Most of the acetaldehyde, a recognized animal carcinogen, generated
      during alcohol metabolism is eliminated by liver mitochondrial aldehyde
      dehydrogenase 2 (ALDH2). More than 40% of Japanese have the inactive form of
      ALDH2, and inactive ALDH2 is a risk factor for multiple cancers of the esophagus
      as well as head and neck cancer. Possible associations between pancreatic cancer
      and ALDH2 gene polymorphism, in conjunction with smoking and/or drinking habits,
      were examined in a Japanese population. METHODS: We investigated 114 patients (70
      male and 44 female) with pancreatic cancer and compared them with 2070 control
      subjects (1050 male and 1020 female). The drinking (5 g ethanol consumption/d)
      and/or smoking habits as well as ALDH2 gene polymorphism were examined. RESULTS:
      In male subjects, the frequency of the active form of ALDH2 (2*1/2*1) was lower
      in pancreatic cancer patients than in control subjects (P = 0.018). The frequency
      of subjects with both smoking and drinking habits was significantly higher in
      pancreatic cancer patients than in control subjects having ALDH2*1/2*1 and
      ALDH2*1/2*2. The frequency of smoking habit alone was significantly higher in
      pancreatic cancer patients compared with control subjects having inactive ALDH2.
      Drinking habit had no relation to pancreatic cancer. In female subjects, neither
      habit had a relation to pancreatic cancer. CONCLUSIONS: Smoking habit did
      increase the risk of pancreatic cancer, and this risk was further enhanced in
      subjects with inactive ALDH2 in a male population but not in a female population.
      There was no relationship between drinking habit and pancreatic cancer in either
      sex population.

PMID- 15714131
TI  - Enhanced citrate synthase activity in human pancreatic cancer.
AB  - OBJECTIVES: Assuming that a high flux of carbohydrate is strictly connected with
      lipid synthesis in neoplastic cells, one can hypothesize that the activity of
      citrate synthase, which plays an important role in glucose to lipid conversion,
      is enhanced in pancreatic cancer. The aim of the present study was to verify this
      hypothesis. METHODS: The activity of citrate synthase (as well as lactate and
      glucose 6-phosphate dehydrogenases) was measured using tissue extract prepared
      from specimens (pancreatic cancer and control specimens taken from the adjacent
      pancreatic normal tissue) obtained from 24 patients with ductal carcinoma who
      underwent pancreatoduodenectomy or total pancreatomy. RESULTS: The average of
      citrate synthase activity in human pancreatic ductal carcinoma is significantly
      higher comparing with adjacent nonneoplastic tissue: 40.2 +/- 27.2 and 18.3 +/-
      13.6 nmole/min/mg protein, respectively (P = 0.001). The lactate dehydrogenase
      and glucose 6-phosphate dehydrogenase activity in human pancreatic ductal
      carcinoma were also higher than in adjacent nonneoplastic tissues. CONCLUSION: It
      is likely that enhanced citrate synthase activity contributes to the conversion
      of glucose to lipids in pancreatic cancer providing substrate for membrane lipids
      synthesis.

PMID- 15714132
TI  - Tumor necrosis factor-related apoptosis-inducing ligand and CD56 expression in
      patients with type 1 diabetes mellitus.
AB  - OBJECTIVES: Our previous report showed that beta-cell antigen-specific CD56+ T
      cells and cytokine TRAIL mediate destruction of human pancreatic [beta] cells in
      vitro. To determine whether CD56 and TRAIL are present during islet cell
      destruction at the onset of clinical symptoms of type 1 diabetes mellitus (T1D),
      we studied cell marker and cytokine expression in the pancreatic islets of 2
      children who died at presentation of acute-onset T1D and in T-cell lines derived
      from a group of children with new-onset T1D. METHODS: TRAIL, CD56, and other T
      cell markers and cytokine expression were studied using immunohistochemistry on
      pancreatic sections from 2 children with acute-onset T1D. TRAIL and CD56
      expression was analyzed by flow cytometry in the antigen-activated T-cell lines
      derived from 29 children with new-onset T1D. RESULTS: TRAIL+, CD56+, CD45RO+, and
      CD3+ cells were present in the islets of acute-onset T1D patients, while none
      were present in the normal islets. T-cell lines from new-onset T1D expressed
      TRAIL and CD56 in response to stimulation with beta-cell antigens GAD, IA-2 and
      insulin beta chain. CONCLUSION: The presence of TRAIL and CD56 markers is part of
      the T-cell response repertoire in beta-cell destruction.

PMID- 15714133
TI  - Intraductal tubular neoplasms of the pancreas: histogenesis and differentiation.
AB  - OBJECTIVES: Intraductal neoplasms of the pancreas are generally referred to as
      intraductal papillary mucin-producing neoplasms (IPMNs), according to the WHO
      classification system. Herein, we report that morphologic and immunohistochemical
      features of intraductal tubular carcinoma (ITC) are quite different from those of
      intraductal papillary mucinous carcinoma (IPMC). METHODS: We analyzed
      histogenesis and differentiation of ITC by light microscopy and
      immunohistochemistry. RESULTS: Histologically, ITC was characterized as an
      intraductal nodular appearances with a monotonous tubular growth pattern without
      papillary projection. ITC showed de novo-like appearance without sequential
      progression usually observed in IPMC, suggesting that ITC is a homogeneous
      neoplasm. Cuboidal tumor cells in ITC resembled normal pancreatic duct epithelia,
      and the characteristic growth pattern of ITC replaced that of normal pancreatic
      duct epithelium. Immunohistochemically, ITC cells were positive for MUC-1 on the
      apical side of the cell membrane. In contrast to ITC cells, IPMC cells were
      negative for MUC-1, and ductal adenocarcinoma cells were strongly positive for
      MUC-1, as was the stroma around the cancer. The immunohistochemical staining
      pattern of DUPAN-2 resembled that of MUC-1. Interestingly, localization of MUC-1
      and DUPAN-2 staining in ITC cells was similar to that in normal pancreatic
      ductules. ITC cells were negative for MUC-2 and MUC-5AC. In contrast, most IPMC
      cells were positive for MUC-2 and MUC-5AC. CONCLUSION: Based on our histologic
      and immunohistochemical findings, the intraductal pancreatic neoplasm (IPN) can
      be classified into 2 groups: IPN with gastrointestinal differentiation and IPN
      with pancreatic duct differentiation. Our present data indicated that ITC cells
      may arise directly from duct epithelia without progression and possessed
      pancreatic duct differentiation. On the basis of our data, we suggest that
      classification of pancreatic neoplasms in the WHO and The Armed Forces Institute
      of Pathology (AFIP) systems should be reconsidered.

PMID- 15714134
TI  - Innate immune responses to adenoviral vector-mediated acute pancreatitis.
AB  - OBJECTIVES: The role of innate immunity in the development of acute viral
      pancreatitis is not well understood. The aim of the study was to characterize the
      role of the innate immune system, especially macrophages, natural killer (NK),
      and NK T (NKT) cells, in the generation of immune responses to intrapancreatic
      delivery of recombinant adenoviral vector. METHODS: Adenoviral vectors expressing
      beta-galactosidase or green fluorescent protein genes with viral capsid
      conjugated covalently with carbocyanine dye were directly injected into the
      pancreas of C57Bl/6 mice. RESULTS: Fluorescent microscopy of the pancreas showed
      that 30 minutes after vector administration, adenoviral particles localized to
      cell membranes, internalized, and localized to the nucleus by 4 hours, and
      transgene expression began at 24 hours. Immunohistochemical staining showed
      macrophages entering the pancreas shortly after vector administration, with
      maximal infiltration at day 4, and then disappearing as antigen-expressing cells
      were eliminated. Intrapancreatic macrophages appeared to deliver viral capsid
      proteins to the spleen. Flow cytometry showed that NK and NKT cells migrate to
      the pancreas and persist. Serum cytokines IL-6, IL-10, and IL-12 were all
      elevated. CONCLUSION: Macrophages and NK and NKT cells play a major role in the
      development of acute adenovirus-mediated pancreatitis.

PMID- 15714135
TI  - Reversal of diabetes by xenotransplantation of monkey pancreatic islets in rats:
      an ultrastructural study.
AB  - OBJECTIVES: Transplantation of pancreatic islets is considered a potential
      curative treatment of type 1 diabetes. Electron microscopy plays a major role in
      the evaluation of pancreatic islets. The aim of this study was to study the
      reversal of diabetes by xenotransplantation of monkey pancreatic islets into
      diabetic recipient by functional and structural findings. METHODS: Islets of
      Langerhans were isolated from monkeys by collagenase digestion method. Two days
      after the induction of diabetes in rats with streptozotocin, diabetes was
      confirmed. Freshly isolated islets were transplanted under the renal capsule of
      the diabetic rats. The recipients received cyclosporin A (30 mg/kg) every day.
      Fasting plasma glucose was estimated on days 3, 7, and 14 after transplantation.
      The presence of glucose and ketone in urine was checked. After 14 days, the
      grafts were removed and processed for light and electron microscopic study.
      RESULTS: After the induction of diabetes, the mean fasting plasma glucose was
      347.20 mg/dL. On day 3 after transplantation, the mean fasting plasma glucose
      value was 100 mg/dL. The mean fasting plasma glucose was 94.6 mg/dL on day 7 and
      94.8 mg/dL on day 14. Histology of the monkey islet grafts after 14 days showed
      the survival of pancreatic islets. Ultrastructure of the same grafts showed the
      presence of alpha, beta, and delta granules similar to those of native pancreatic
      islets with the other cellular organelles. CONCLUSION: The diabetic state of rats
      can be reversed by xenotransplantation of isolated monkey islets. Ultrastructural
      study confirms the normal synthesis and release of islet hormones. The released
      insulin from transplanted monkey islets had lowered the plasma glucose level of
      recipient rats.

PMID- 15714136
TI  - Impact of porcine islet size on cellular structure and engraftment after
      transplantation: adult versus young pigs.
AB  - OBJECTIVES: To study the impact of porcine islet size on structural properties
      and cellular engraftment. METHODS: The endocrine structure and collagen/vascular
      localization in pig islets were studied before and after enzymatic isolation on
      the pancreas from 6 young and 6 adult Landrace pigs. Isolated islets from both
      pig types were transplanted under the kidney capsula of diabetic nude rats to
      assess cellular engraftment. RESULTS: In comparison with adult pig pancreata, a
      significantly greater number of small beta cells (<100 microm) were observed
      before and after isolation (82% vs. 32%, respectively, P < 0.005) from young pig
      pancreata. Small islets (<100 microm) showed a peripheral vascular structure,
      whereas large islets showed a more centralized vascular organization, thereby
      providing protection during the enzymatic digestion procedure. The islet
      endocrine structure was not affected by the islet size, but a loss of glucagon
      cells (-7.9%, P < 0.005) was observed in large isolated islets. The purity of
      islet preparation was better with pancreata from adult than young donors (86% vs.
      64%, respectively, P < 0.05). A lack of engraftment was observed for small islets
      from young pig donors as compared with large islets from adult donors.
      CONCLUSIONS: Large and well-structured islets, mainly found in adult pig
      pancreata, probably possess a better potential for cellular engraftment due to
      centralized vascularization and collagen distribution.

PMID- 15714137
TI  - Improved retention of zymogen granules in cultured murine pancreatic acinar cells
      and induction of acinar-ductal transdifferentiation in vitro.
AB  - OBJECTIVES: To establish a primary culture model for murine pancreatic acinar
      cells and to investigate the effects of different culture conditions on the
      phenotype and plasticity of these cells in extended culture. METHODS: Acinar
      cells, cultured in Chee (CME) or Waymouth/Ham F-12 (WHME) media, exhibited 2
      markedly dissimilar phenotypes. We employed 5'-bromo-2'-deoxyuridine (BrdU)
      incorporation, immunocytochemistry, and electron microscopy to investigate
      differences in cell cycle status and phenotype. RESULTS: CME-cultured cells grew
      as discrete epithelial islands and retained zymogen granules and endoplasmic
      reticulum stacks, yet expressed cytokeratin 7, suggesting that they comprise an
      intermediate between the acinar and ductal cell types. Observed by time-lapse
      videomicroscopy, cells transferred to WHME formed a confluent monolayer,
      flattened and dedifferentiated to a duct-like phenotype typified by loss of
      secretory apparatus, variable beta-catenin expression, an elongated teardrop
      shape, increased cell size, and nuclear pleomorphism. Transition between
      phenotypes did not involve apoptosis as assessed by morphologic criteria in
      Feulgen-stained cultures. The flattened cells exhibited increased BrdU
      incorporation and mitotic index, suggesting that dedifferentiation precedes the
      capacity for increased cell cycle entry, while the appearance of meganuclei is
      consistent with amplified DNA content. We also demonstrate greatly improved gene
      delivery to cultured acinar cells by adenovirus-mediated transduction compared
      with lipid-mediated transfection. CONCLUSIONS: This in vitro model confirms the
      plasticity of acinar cells and may serve to delineate the changes underlying
      acinar cell dedifferentiation and acquisition of a duct-like pluripotent
      phenotype.

PMID- 15714138
TI  - RPL38, FOSL1, and UPP1 are predominantly expressed in the pancreatic ductal
      epithelium.
AB  - OBJECTIVES: Establishing more effective treatment of pancreatic cancer requires
      an understanding of the molecular events leading to the onset and progression of
      this disease. The biology of tumorigenesis may be better understood if cell type
      specific genes in the pancreas are more recognized. This recognition may be as
      important as discovering a disease-responsible gene. Identification of a ductal
      epithelium-specific gene can contribute not only to our knowledge of pancreatic
      tumorigenesis, tumor marker discovery, and effective drug targeting but also is
      crucial for making a reliable animal model. METHODS: We used the x-Profiler
      engine online to compare the SAGE (Serial Analysis of Gene Expression) libraries
      derived from 2 short-term cultures of normal human ductal epithelial cells from
      the pancreas against 34 other SAGE libraries generated from other normal human
      tissues to identify the best candidate gene specific for the ductal epithelium of
      the pancreas. RESULTS: We identified 3 genes, ribosomal protein L38 (RPL38),
      uridine phosphorylase (UPP1), and FOS-like antigen-1 (FOSL1), predominantly
      expressed in the pancreatic ductal epithelium. The expression patterns of these 3
      genes were confirmed by virtual Northern analysis, semi-quantitative RT-PCR, and
      in situ hybridization. CONCLUSION: Although the expressions of these 3 genes are
      not completely restricted to the ductal epithelium of the pancreas, we showed
      that they have more specific expression patterns than CK19 and MUC1. We also
      demonstrated that all 3 genes are highly expressed in a panel of pancreatic
      cancer cell lines and can potentially be useful in tumor targeting or as tumor
      markers.

PMID- 15714139
TI  - Analysis of E-, N-cadherin, alpha-, beta-, and gamma-catenin expression in human
      pancreatic carcinoma cell lines.
AB  - OBJECTIVES: Cadherins are cell surface glycoproteins that mediate Ca2+-dependent,
      homophilic cell-cell adhesion. The classic cadherins interact with either beta
      catenin or gamma-catenin, which is bound to alpha-catenin that links the complex
      to the actin cytoskeleton. It has been reported that alteration in
      cadherins/catenins function or expression is found in the neoplastic process as a
      step in metastasis. The aim of this study was to analyze the expressions of E-
      and N-cadherins and catenins in human pancreatic cancer cell lines. METHODS: We
      examined the expression of cadherins and catenins in 7 human pancreatic cancer
      cells by RT-PCR, Western blotting, and immunocytochemistry. The interactions
      between cadherins and beta-catenin were assessed by immunoprecipitation. RESULTS:
      E-cadherin was expressed in all cell lines except for MIAPaCa-2, whereas N
      cadherin was expressed in Capan-2, CFPAC-1, BxPC-3, and PANC-1. The alpha-, beta
      , and gamma-catenins were expressed and cadherins/beta-catenin interactions were
      detected in all cadherin-expressing cells. Immunocytochemical analysis showed
      membranous expression of cadherins and catenins. CONCLUSION: The decreased or
      loss of cadherins and catenins expression could be involved in the tumor
      progression and metastasis, although these events may occur in in vivo conditions
      by interaction between cancer cells and extracellular matrices.

PMID- 15714140
TI  - Regeneration of tubular complex is promoted by a free space.
AB  - OBJECTIVES: Regeneration of the pancreas is initiated by the tubular complexes
      that consist of a cluster of epithelia surrounded by the mesenchymal cells. They
      have the potential to become pancreatic lobes, but their growth stops before the
      complete regeneration of the organ. To elucidate the possibility that we could
      promote the regeneration of the pancreas, the potential for growth or
      differentiation of tubular complex was analyzed. METHODS: The intact lobes were
      growing around the silk knot after ligation of the pancreas in adult mice. To
      develop this reaction to a quantitative assay, tubular complexes were induced on
      the silk strings in the pancreas and were growing into a free space under the
      silicon cover. The proliferation and differentiation of new lobes with or without
      the space were analyzed. RESULTS: The number of tubular complexes, which express
      PDX-1, was increased 5.4 times by the space effect. The proliferating cell
      nuclear antigen labeling index of acinar cells was 1.7 times stimulated, but that
      of tubular complex was not changed. The amputated pancreas recovered 49.5% of the
      resected part under the silicon cover; however, it remained the same weight
      without the cover. CONCLUSION: The proliferation and differentiation of tubular
      complex are promoted by a free space.

PMID- 15714141
TI  - Enzyme content and acid stability of enteric-coated pancreatic enzyme products in
      vitro.
AB  - OBJECTIVES: Pancreatic enzymes are prescribed routinely for pancreatic
      insufficiency. In the current health care environment, drug substitution is
      commonly performed although there is no proof of therapeutic or bioequivalence
      for these products. The purpose of this in vitro, prospective study was to
      evaluate the enzyme contents and dissolution of various capsules of pancreatic
      enzyme using current United States Pharmacopoeia (USP) methodology. METHODS: Nine
      different pancreatic enzyme products were purchased on the market and supplied to
      Irvine Analytical Laboratories (IAL) (Irvine, CA). All test products were
      maintained in the laboratory environment, at room temperature, throughout the
      testing period by IAL. USP procedures for assay and dissolution testing of
      pancrelipase delayed-release capsules, as described in the latest USP supplement
      were observed during product testing, including determination of amylase, lipase,
      and protease activity. In addition, a point assay with measurement of lipase
      after dissolution in simulated gastric fluid pH of 1.0 for 1 hour and then
      dissolution in pH 6 phosphate buffer for 30 minutes performed in accordance with
      USP guidelines. RESULTS: Assay results of amylase, protease, and lipase from the
      9 tested products are within USP specified limits. The percentage of label claim
      for these enzymes was higher than depicted in their label except for one drug
      batch. However, the percentage of lipase activity after dissolution varied with 2
      of 3 batches of 1 drug not dissolving, and 1 batch of another drug, revealing
      only 8% lipase activity in the USP dissolution test. CONCLUSION: While assay of
      pancreatic enzymes reveal they were equal to their USP claims regarding their
      enzyme content, not all pancreatic enzyme replacements are equal in their release
      of lipase activity according to USP requirements. The findings maybe clinically
      seen with therapeutic failures of enzyme products. The FDA has recently decreed
      that all pancreatic enzyme products will require an approved NDA as differences
      in pharmaceutical quality have been identified in this product. Thus, it is
      considered that substitution of these products maybe questionable. Things are
      seldom what they seem- not all pancreatic enzyme replacements are equal. Further
      studies are warranted to investigate dissolution characteristics.

PMID- 15714142
TI  - Clear cell carcinoma of exocrine pancreas: a rare tumor with an unusual
      presentation.
AB  - Metastatic clear cell carcinomas are relatively common from primary tumors
      arising in the kidney, female genital tract, adrenal cortex, and lung, but they
      rarely occur from primary tumors of the pancreas. We report a case of metastatic
      pancreatic tumor with marked clear cell changes in a 46-year-old white man
      presenting with a pseudocyst of the pancreas. At laparotomy, there was a hard
      area in the head of the pancreas and another hard nodule was present in the
      omentum. The histologic and immunohistochemical test of the excised omental
      nodule exhibited features consistent with clear cell carcinoma from pancreatic
      primary. To our knowledge, this is the first report of a metastatic clear cell
      pancreatic tumor with such an unusual presentation.

PMID- 15714143
TI  - Huge mucinous cystadenoma of the pancreas developing during pregnancy: a case
      report.
AB  - A 33-year-old woman, gravida 2, para 1, was found to have a huge intra-abdominal
      cyst (2619 ml) in the 15th week. The cyst increased in volume to 3660 ml during
      the next 31 days. A tentative diagnosis of ovarian or pancreatic mucinous
      cystadenoma was made. Since the cyst was considered to cause fetal intra-uterine
      growth restriction, the patient underwent surgery in the 23rd week of pregnancy.
      The cyst was found to originate from the pancreas, and distal pancreatectomy with
      splenectomy was performed. The specimen weighed 5500 gm, which is the largest so
      far reported. Her postoperative course was uneventful, and she had a healthy full
      term infant. Histological diagnosis was a benign mucinous cystadenoma. Up to the
      present, there have been three reported cases of pancreatic mucinous cystadenoma,
      including our case, and two cases of pancreatic mucinous cystadenocarcinoma, in
      association with pregnancy. Our case is the third reported of successful
      resection of the tumor during pregnancy resulting in a healthy infant.

PMID- 15714144
TI  - A new fecal elastase 1 test using polyclonal antibodies for the detection of
      exocrine pancreatic insufficiency.

PMID- 15714145
TI  - Autoantibodies against the exocrine pancreas in fulminant type 1 diabetes.

PMID- 15714146
TI  - Autoimmune pancreatitis, Helicobacter pylori infection, and apoptosis: a proposed
      relationship.

PMID- 15714147
TI  - Contemporary minimally invasive approaches to the management of acute
      cholecystitis: a review and appraisal.
AB  - Acute cholecystitis is one of the most common emergency admissions in surgical
      practice. This review appraises the available evidence from the English-language
      literature regarding the minimally invasive approaches to the management of this
      condition. The following aspects of care are reviewed and appraised: (1) the
      diagnostic criteria for acute cholecystitis, (2) the optimal timing for
      cholecystectomy (early, delayed, or interval surgery), (3) the optimal approach
      to cholecystectomy (laparoscopic versus open), (4) the role of intraoperative
      cholangiography, and (5) the management of patients unfit for surgery.

PMID- 15714148
TI  - Safety and efficacy of the use of bioabsorbable seamguard in colorectal surgery
      at the Texas endosurgery institute.
AB  - Bioabsorbable Seamguard (BSG) is a random-fiber web of polyglycolic
      acid/trimethylene carbonate. It is completely absorbed within 6 months or less
      due to its constitution of a bioabsorbable membrane with polyester braided
      suture. It has been used in obesity surgery and pulmonary surgery as staple-line
      reinforcement with good results. As such, we believe that BSG may be ideal to use
      in colorectal surgery as an aid during the healing process of an anastomosis and
      may help prevent anastomotic bleeding and staple-line disruption. From July 2003
      through September 2004, 30 patients underwent placement of BSG for the following
      procedures: 12 right hemicolectomies, 7 low anterior resections, 5 sigmoid
      colectomies, 3 total colectomies, 2 partial resections, and 1 colostomy closure.
      Median follow-up was 7 months (range 1-13). There were no clinical leaks, no
      strictures, and no bleeding in our early postoperative follow-up period. The use
      of BSG as a staple-line reinforcer appears to be safe and may be useful in
      preventing anastomotic leakage, bleeding, and intraluminal stenosis.

PMID- 15714149
TI  - The role of laparoscopy in penetrating abdominal stab wounds.
AB  - The role of diagnostic laparoscopy (DL) in abdominal stab wounds (ASWs) is not
      clearly defined. We hypothesized that peritoneal penetration (PP) during DL was a
      valid indication to convert to an exploratory laparotomy (EL). Retrospective
      review of hemodynamically stable ASWs requiring operation. A total of 161
      patients with ASWs were identified, with 36 of 92 patients (39.1%) undergoing DL
      converted to EL. All 36 patients had PP; 20 of 36 (55.6%) ELs were therapeutic
      (TL). The number of nontherapeutic laparotomies (NTLs) prevented was 56 (60.9%).
      Five of 92 patients had PP on DL but did not undergo EL. Twenty-four of 69
      patients who underwent initial EL had an NTL (34.8%). If this group had undergone
      an initial DL, and PP was used to determine need for EL, the number of NTLs would
      have been reduced to 10 (14.5%), a 58.3% reduction. Evidence of PP during DL is a
      reasonable indicator to determine the need for EL and reduce the number of NTLs.

PMID- 15714150
TI  - Instrumentation for laparoscopic renal surgery--Padron Endoscopic Exposing
      Retractor (PEER) and Endoholder: point of technique.
AB  - During laparoscopic surgery, as in open surgery, exposure is critical. However,
      this can be difficult during laparoscopy due to limited haptic feedback and the
      loss of 3-dimensional visualization. Excessive force may be inadvertently applied
      by assistants when anatomic structures are retracted; similarly, the retractors
      may be unknowingly moved because the limited field of view with the laparoscope
      precludes constant visualization of the retracting instrument. To overcome these
      problems, we have been using a 5- or 10-mm PEER retractor in combination with an
      articulating arm instrument holder (Endoholder) to aid laparoscopic renal
      surgery. The adjustable spring-loaded articulating instrument holder (Endoholder)
      consists of 4 components, including table attachment, a base rod, flexible
      extension arm, and precision clamp. The clamp accommodates variously sized
      instruments, and the flexible extension arm rotates 360 degrees to aid in
      positioning. The instrument holder is clamped to the table via the base rod over
      a sterile drape. A PEER Retractor, Roto-lok ratchet (5- or 10-mm diameter and 32
      cm length) is placed intracorporeally to retract and position the kidney for
      hilar, upper, and lower pole dissection. The PEER retractor's handle is secured
      in place using the precision clamp of the instrument holder. The articulating
      instrument holder and PEER retractor are used for our renal, adrenal, and
      ureteral laparoscopic procedures. Placement of the retractor through a 5- or 10
      mm port and deployment can be done quickly. Adequate and stable positioning of
      the retractor provides excellent and secure visualization of the operative field.
      These instruments have been used in more than 200 cases without any complication
      except 1 minor liver laceration. The articulating instrument holder with the PEER
      retractor is a very useful aid during laparoscopic renal surgery. This instrument
      reduces the chances of inadvertent injury to viscera by the assistant while
      maintaining an excellent anatomic view throughout the procedure. This will have a
      significant impact on the advancement of laparoscopy and its acceptance by every
      urologist.

PMID- 15714151
TI  - Remember to crush the tablets after esophageal stent insertion.
AB  - The main mode of palliation for inoperable esophageal cancer is by insertion of
      expandable metallic stents. While major complications include occlusion by tumor
      ingrowth and migration, impaction by food has been reported in as many as 10% of
      cases. Although patients are routinely instructed to follow a soft and finely
      minced diet after insertion of esophageal stents, stent blockage can still occur
      if patients swallow large-sized tablets. We report a case of stent blockage by 2
      large-sized tablets, about which the endoscopist did not forewarn the patient or
      his family. The tablets were eventually dislodged easily through a repeat
      endoscopy. We caution about the possibility of such complication after esophageal
      stenting. We recommend inspection of patients' medication before the stenting
      procedure as well as instructing patients, their family, and care providers to
      crush their large-sized tablets before consumption.

PMID- 15714153
TI  - Laparoscopic procedures in adults with ventriculoperitoneal shunts.
AB  - Until recently, the presence of a ventriculoperitoneal shunt (VPS) was considered
      an absolute contraindication to laparoscopy. In some cases, intraabdominal
      insufflation causes a rapid, sustained increase in intracranial pressure (ICP).
      Such intracranial hypertension may result in hindbrain herniation. To prevent
      this, the use of lower abdominal pressures, intraoperative ICP monitoring,
      intraoperative ventricular drainage, and distal shunt catheter
      clamping/externalization has been reported in some studies. However, other
      studies show that laparoscopy is safe even without VPS catheter clamping and with
      only routine anesthetic monitoring. Moreover, the risk of retrograde failure of
      the valve system has been shown to be minimal even with intraabdominal pressures
      as high as 80 mm Hg. We report how we managed a hydrocephalic adult with a VPS
      shunt undergoing laparoscopic cholecystectomy in the hope that our experience
      contributes to the successful management of such patients in the future.

PMID- 15714152
TI  - Laparoscopic removal of gastric band after early gastric erosion: case report and
      review of the literature.
AB  - Laparoscopic gastric banding is a popular method for treating morbid obesity. One
      of the most serious complications is band erosion into the gastric lumen. We
      present the case of a patient who underwent gastric banding and presented with
      symptoms of gastrointestinal reflux and mild-to-moderate hypertension, fever, and
      pain. UGI revealed stomach wall erosion and partial migration of the band into
      the gastric lumen. The band was laparoscopically removed without any further
      complications. Migration after laparoscopic gastric banding must be immediately
      addressed to prevent infection. Close monitoring of the band location during
      adjustments as well as a high index of suspicion is necessary.

PMID- 15714154
TI  - Laparoscopic-assisted management of small bowel obstruction due to phytobezoar.
AB  - Laparoscopy is gaining increasing acceptance for diagnosis and treatment of
      selected cases of small bowel obstruction. We describe a laparoscopic-assisted
      procedure used for the treatment of small bowel obstruction caused by a bezoar. A
      51-year-old man presented with acute small intestinal obstruction. He had no
      history of previous abdominal surgery. Diagnostic laparoscopy confirmed a distal
      ileal obstruction due to an enterolith (bezoar). A limited abdominal incision
      allowed enterotomy and removal of the obstructing bezoar. Gastroscopy performed a
      month later showed gastric bezoars which could not be removed endoscopically.
      Instead, cellulase, a hydrolytic enzyme, was used successfully to treat the
      condition.

PMID- 15714155
TI  - Laparoscopic treatment of an omental cyst: a case report and review of the
      literature.
AB  - The authors evaluated the role of a laparoscopic approach on a complete resection
      of an omental cyst. A young female patient (25 years of age) underwent a complete
      resection of a 12-cm omental cyst via a laparoscopic approach. The patient
      presented with vomiting, nausea, and pain in the periduodenal area. The lesion
      was diagnosed via CT and MRI. The authors used four trocars (2 x 10 mm, 2 x 5
      mm). After complete resection and aspiration, the cyst was removed in a bag. The
      postoperative period was uneventful, and the patient was discharged after 48
      hours. There was no sign of relapse after 30 months of follow-up. Mesenteric and
      omental cysts are congenital abdominal lesions. Therefore, a complete resection
      is mandatory because of the high incidence of relapse. A laparoscopic operation
      proves a suitable approach because of the advantages of lower costs and
      comparable results to open surgery.

PMID- 15714156
TI  - Laparoscopic diagnosis and management of primary bacterial peritonitis.
AB  - Primary bacterial peritonitis is a rare condition occurring, by definition, in
      patients without an underlying cause as is otherwise observed in patients with
      perforated viscus, pre-existing ascites, or nephrosis. The diagnosis is usually
      made at laparotomy. Laparotomy, however, is often associated with significant
      morbidity and wound complications. We report a case of primary bacterial
      peritonitis diagnosed at laparoscopy that was managed successfully by
      laparoscopic peritoneal lavage and appropriate antibiotic therapy with
      expeditious recovery. This is yet another argument for the application of
      laparoscopy in the management of generalized peritonitis.

PMID- 15714157
TI  - Pneumothorax: an uncommon complication of minimally invasive parathyroidectomy.
AB  - The gold standard for the surgical treatment of primary hyperparathyroidism has
      traditionally been bilateral neck exploration with identification of all four
      parathyroid glands. However, because of the increasing sensitivity and accuracy
      of preoperative imaging techniques, including ultrasound and sestamibi scanning,
      and the introduction of intraoperative parathyroid hormone monitoring, unilateral
      neck exploration has become more widely used. We describe two cases of
      pneumothorax following minimally invasive parathyroidectomy. The pneumothorax in
      the first case was thought to be due to the position of the parathyroid adenoma
      in the mediastinum and thus its close proximity to the lung pleura. In the second
      case, the patient had a history of emphysema, and the pneumothorax was most
      likely due to a rupture of a bleb. With prompt diagnosis and early treatment of
      this potential complication, morbidity can be decreased.

PMID- 15714158
TI  - Laparoscopy-assisted percutaneous nephrolithotomy (PCNL) in previously operated
      ectopic pelvic kidney.
AB  - A 35-year-old man with a left ectopic pelvic kidney and a prior history of open
      pyelolithotomy presented with recurrent multiple stones in the pelvic kidney.
      Complete clearance of calculi was achieved by laparoscopy-assisted PCNL
      (percutaneous nephrolithotomy). To the best of our knowledge this is the first
      report of laparoscopy-assisted PCNL in a previously operated ectopic pelvic
      kidney.

PMID- 15714160
TI  - The syndrome of irreversible lithium-effectuated neurotoxicity.
AB  - OBJECTIVES: Persistent sequelae of lithium intoxication gained clinical attention
      in the 1980s and were named Syndrome of Irreversible Lithium-Effectuated
      Neurotoxicity (SILENT). The authors review the published cases of SILENT reported
      in the literature and discuss various clinical manifestations. METHODS: The
      authors' inclusion criteria included persistence of sequelae for at least 2
      months after the cessation of lithium administration. They conducted a MEDLINE
      and Pub Med search for journal articles from the year 1965 to 2004. They also
      cross-referenced available papers. RESULTS: The authors identified 90 cases of
      SILENT in peer-reviewed publications. Persistent cerebellar dysfunction was the
      most commonly reported sequela. Other atypical presentations have also been
      reported. CONCLUSION: Although the biologic mechanism remains unclear, the
      authors hypothesize that the putative cause of SILENT is demyelination caused by
      lithium at multiple sites in the nervous system, including the cerebellum. Recent
      advances in the understanding of the molecular basis of lithium-induced
      neurotoxicity may be able to provide a means of defining a pathway associated
      with the long-term prophylactic properties of lithium, distinct from its toxicity
      profile. This identification of differential gene expression patterns that
      distinguish between therapeutic and toxic actions of lithium may help in the
      discovery of new drugs for mood stabilization. Clinically and heuristically, it
      is important to raise the awareness of this syndrome so that clinicians are able
      to avoid it. A precise definition, operational diagnostic criteria, and a
      descriptive name will aid in the early identification and prevention of SILENT.

PMID- 15714161
TI  - Porcine hematopoietic progenitor cell transplantation in nonhuman primates: a
      review of progress.
AB  - The critical shortage of human donor organs for transplantation would be overcome
      if a suitable animal, e.g., the pig, could be used as an organ source. There are,
      however, several immune barriers that have to date resulted in limited function
      of pig organs transplanted into nonhuman primates. It would be beneficial, and
      indeed may be essential, to induce a state of tolerance in the primate recipient
      to the pig organ. In allotransplantation, the successful transplantation of
      hematopoietic progenitor cells with the development of mixed chimerism is
      associated with the induction of tolerance toward a donor-specific organ. For
      some years, this approach has been explored in the pig-to-nonhuman primate model.
      This experience is briefly reviewed. The problems of natural and elicited anti
      pig antibodies, recipient platelet adhesion to pig hematopietic progenitor cells,
      and the rapid removal of these cells by the host macrophage-phagocytic system are
      highlighted. Recent experience with the use of hematopoietic cells from pigs
      homozygous for alpha1,3-galactosyltransferase gene-knockout is reported.

PMID- 15714162
TI  - The best dosing for initial tacrolimus application is trough level adapted!

PMID- 15714163
TI  - Successful use of anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible
      living-related liver transplantation.
AB  - BACKGROUND: Humoral rejection after ABO-incompatible liver transplantation often
      causes graft loss and a life-threatening situation. We used rituximab, which can
      eliminate B cells highly selectively, as an additional therapy for ABO
      incompatible living-related liver transplantation. CASES: Patient 1 was a 1-year
      old girl with biliary atresia. Her blood type was O, and the donor's was A. She
      underwent two plasma exchanges before liver transplantation and had triple
      immunosuppressants (mycophenolate mofetil, tacrolimus, and methylprednisolone).
      She was diagnosed with humoral rejection by needle biopsy on postoperative day 6.
      Rituximab was used for 3 days at 375, 187, and 187 mg/m(2) and successfully
      reduced the antibody titer, transaminase, and CD19(+) cells count in peripheral
      blood lymphocytes. The patient has not had any severe rejection, infection, or
      serious complications 2 years posttransplantation. Patient 2 was a 42-year-old
      woman with primary biliary cirrhosis. The blood type was O, and the donor's was
      B. She received three plasma exchanges, triple immunosuppressants, splenectomy,
      intraarterial anticoagulant therapy, and rituximab (375 mg/m(2) immediately after
      transplantation). The titer and CD19(+) cells count remained persistently low
      throughout the recovery course. She did not develop humoral rejection 1 year
      after transplantation. CONCLUSIONS: Rituximab efficiently reduces anti-ABO
      antibody titer by selectively eliminating B cells and is safe and effective
      against humoral rejection after ABO-incompatible liver transplantation.

PMID- 15714164
TI  - Mechanistic study of malononitrileamide FK778 in cardiac transplantation and CMV
      infection in rats.
AB  - BACKGROUND: FK778 is a malononitrilamide, a class of immune suppressive compounds
      with antiviral features and experimental activity in chronic rejection, a
      potentially interesting combination for organ transplantation. The goal of this
      project was to study the tolerability, immune suppressive efficacy, and anti
      cytomegalovirus (CMV) activity of FK778 and to assess the in vivo relevance of
      its previously described inhibition of de novo pyrimidine synthesis. METHODS:
      Heart transplants were performed in rats (Brown Norway [BN] to Lewis) and treated
      with varying doses of FK778 or leflunomide for 28 days. At 28 days, at the time
      of rejection or at the death of the animal, the allograft and other vital organs
      were obtained for study by light microscopy and immunohistochemistry. In separate
      experiments, Lewis rats were given sublethal irradiation, inoculated with rat CMV
      (Maastricht strain), and treated with varying doses of FK778 and leflunomide. In
      both the transplant and CMV studies, IP uridine was given at 250 mg/kg to cohorts
      or animals receiving FK778 and leflunomide. RESULTS: FK778 controls acute
      rejection and inhibits CMV replication at 20 mg/kg but is toxic at 25 mg/kg.
      Toxicity is manifested as anemia, changes in hepatic and intestinal histology,
      and mortality. The toxicity but not the immune suppressive or antiviral efficacy,
      is reduced significantly by exogenous uridine administration. CONCLUSION: FK778
      has both immune suppressive and antiviral activities, neither of which is
      entirely dependent on inhibition of pyrimidine synthesis. These, and other
      published observations, suggest that the antiviral activity and a considerable
      part of the efficacy of the malononitrilamide family of drugs is attributable to
      activities other than drug induced pyrimidine deficiency.

PMID- 15714165
TI  - CD4(+) T-cell-mediated mechanisms of corneal allograft rejection: role of Fas
      induced apoptosis.
AB  - BACKGROUND: The role of CD4(+) T cells as effector cells in corneal allograft
      rejection is poorly understood. We investigated the role of CD4(+) T cells as
      helper cells in the generation of allospecific effector macrophages in corneal
      graft rejection and the role of CD4(+) T cells as apoptosis-inducing effector
      cells. METHODS: Corneal allografts were transplanted to CD4 knockout, FasL
      deficient, and macrophage-depleted hosts. An Annexin-V binding assay was used to
      evaluate the susceptibility of corneal cells to both Fas-dependent and CD4 T-cell
      mediated apoptosis in vitro. RESULTS: Macrophages were essential for graft
      rejection, but not as effector cells. Anti-BALB/c CD4(+) T cells from immunized
      C57BL/6 mice induced apoptosis of BALB/c corneal epithelial and endothelial
      cells. However, anti-BALB/c CD4(+) T cells from FasL-deficient gld/gld mice did
      not induce apoptosis of BALB/c corneal endothelial cells. Moreover, gld/gld mice
      had a reduced capacity to reject BALB/c corneal allografts. Although the initial
      results suggested a role for Fas-induced apoptosis in corneal graft rejection,
      additional experiments indicated otherwise. The incidence and tempo of immune
      rejection of Fas-deficient lpr/lpr corneal allografts were no different than
      those for corneal grafts from Fas-bearing C57BL/6 donors. Moreover, CD4(+) T-cell
      mediated apoptosis of corneal cells could not be blocked with either Fas-Fc
      fusion protein or anti-FasL blocking antibody. CONCLUSIONS: The results suggest
      that CD4(+) T cells function directly as effector cells and not as helper cells
      in the rejection of corneal allografts. Although the corneal endothelium is
      highly susceptible to Fas-induced apoptosis, this is apparently not the primary
      mechanism of CD4(+) T-cell-dependent rejection.

PMID- 15714166
TI  - Hematopoietic microchimerism in sheep after in utero transplantation of cultured
      cynomolgus embryonic stem cells.
AB  - BACKGROUND: Although directed differentiation of human embryonic stem (ES) cells
      would enable a ready supply of cells and tissues required for transplantation
      therapy, the methodology is limited. We have developed a novel method for
      hematopoietic development from primate ES cells. We first cultured cynomolgus
      monkey ES cells in vitro and transplanted the cells in vivo into fetal sheep
      liver, generating sheep with cynomolgus hematopoiesis. METHODS: Cynomolgus ES
      cells were induced to mesodermal cells on murine stromal OP9 cells with multiple
      cytokines for 6 days. The cells (average 4.8 x 10 cells) were transplanted into
      fetal sheep in the liver (n=4) after the first trimester (day 55-73, full term
      147 days). The animals were delivered at full term, and two of them were
      intraperitoneally administered with human stem-cell factor (SCF). RESULTS:
      Cynomolgus hematopoietic progenitor cells were detected in bone marrow at a level
      of 1% to 2% in all four sheep up to 17 months posttransplant. No teratoma was
      found in the lambs. After SCF administration, the fractions of cynomolgus
      hematopoiesis increased by several-fold (up to 13%). Cynomolgus cells were also
      detected in the circulation, albeit at low levels (<0.1%). CONCLUSIONS: Long-term
      hematopoietic microchimerism from primate ES cells was observed after in vitro
      differentiation to mesodermal cells, followed by in vivo introduction into the
      fetal liver microenvironment. The mechanism of such directed differentiation of
      ES cells remains to be elucidated, but this procedure should allow further
      investigation.

PMID- 15714167
TI  - Influence of collagenase loading on long-term preservation of pig pancreas by the
      two-layer method for subsequent islet isolation.
AB  - BACKGROUND: The introduction of the two-layer method (TLM) for long-term human
      pancreas preservation revealed the enormous potential of TLM to improve graft
      function of isolated islets. It is still unclear whether pig islets can be
      successfully isolated from pancreases after prolonged cold ischemia. To clarify
      this question, pig pancreases were subjected to 7-hour preservation by University
      of Wisconsin solution (UWS) storage or TLM. Another aim was to verify whether TLM
      can be synergistically combined with intraductal collagenase injection before
      cold storage. METHODS: After intraductal flush with UWS, organs were distended
      with 4.4 PZ-U/g of UWS-dissolved collagenase NB-8 and neutral protease adjusted
      to respectively 1.1, 0.2, 0.5, or 0.8 DMC-U/g for pancreases freshly procured
      (n=6) or distended with enzymes before (TLM preloaded, n=7) or after cold storage
      (UWS storage, n=4; TLM postloaded, n=10). RESULTS: Purified islet yield decreased
      from 429,200+/-86,700 islet equivalents (IEQ) in unstored pancreases to
      respectively 37,670+/-19620, 210,400+/-22900 and 238,000+/-26600 IEQ in UWS
      stored (P<0.01), TLM-preloaded, or postloaded organs (P<0.05). Purity (>90%),
      viability (>95%), and insulin content were not different between groups. Islets
      from UWS-stored pancreases fragmented extensively, preventing further assessment
      of in vivo function. Compared with other experimental groups, islets from TLM
      preloaded organs were characterized by enhanced basal and stimulated insulin
      release. Sustained normoglycemia was observed in diabetic nude mice transplanted
      with islets from TLM-postloaded or unstored pancreases in contrast with transient
      function in TLM-preloaded islets. CONCLUSIONS: This study demonstrates that
      significant amounts of intact pig islets can be isolated after prolonged pancreas
      preservation by TLM. Enzyme administration before TLM preservation decreases
      islet graft function.

PMID- 15714168
TI  - CD62 blockade with P-Selectin glycoprotein ligand-immunoglobulin fusion protein
      reduces ischemia-reperfusion injury after rat intestinal transplantation.
AB  - BACKGROUND: Intestinal transplantation (ITx) is severely limited by ischemia
      reperfusion (I/R) injury. This study investigates I/R injury and ameliorates its
      consequences by using a recombinant protein targeted against selectins
      (recombinant P-selectin glycoprotein ligand-immunoglobulin [rPSGL-Ig]). METHODS:
      An isogeneic model of ITx was undertaken with control animals (no therapy) and
      treatment animals (rPSGL-Ig). Survival was assessed. Separate groups underwent an
      analysis examining tissue at multiple time points after I/R injury including
      histopathology; myeloperoxidase staining; immunostaining for CD3 and ED2;
      polymerase chain reaction analysis of interleukin (IL)-8/cytokine-inducible
      neutrophil chemoattractant, IL1beta, IL-6, interferon-gamma, IL-2, IL-4, and
      IL10; and western blots for hemoxygenase-1, BCL-2, and BCL-xl. Standard
      statistical analysis was undertaken. RESULTS: Treatment with rPSGL-Ig resulted in
      significantly improved survival after ITx. Analysis demonstrated diminished
      injury on histopathology and reduced tissue infiltration of neutrophils and
      lymphocytes. Significant differences in the cytokine profile after ITx were seen
      between the two groups including the production of inflammatory cytokines at 24
      hr and the Th1 and Th2 cytokines at 2 and 4 hr. Last, treatment resulted in
      increased production of hemoxygenase, BCL-2, and BCL-xl. CONCLUSION: The results
      of this investigation of I/R injury after ITx revealed that rPSGL-Ig treatment
      led to marked improvement in outcome. The mechanism of action seems to involve
      the blockade of neutrophil and lymphocyte infiltration leading to a decreased
      inflammatory response possibly driven by Th2 cytokines. The results not only lend
      insight into the mechanisms behind I/R injury after ITx but also demonstrate a
      potential therapeutic modality to ameliorate its consequences.

PMID- 15714169
TI  - Long-term normoglycemia in rats receiving transplants with encapsulated islets.
AB  - BACKGROUND: To follow up on previously successful transplantation of encapsulated
      islets in mice, the present study was performed in rats to determine the effects
      of several factors, including alginate composition and concentration of cross
      linking agent and capsule size on the effectiveness of encapsulated islets.
      METHODS: Highly purified alginate of either high guluronic acid or high
      mannuronic acid (M) with low endotoxin content was used. Regular-size (0.8-1.1
      mm) or small microcapsules (0.5-0.7 mm) were produced by cross-linking with BaCl2
      without additional poly-L-lysine coating and were transplanted into abdominal
      cavity of normoglycemic (empty capsules) or streptozotocin induced diabetic Lewis
      rats (islet containing capsules). RESULTS: Empty regular-size capsules made of
      different alginate compositions had similar biocompatibility and stability
      results. Compared with empty capsules, regular-size capsules made of high-M
      alginate containing syngeneic islets had inferior stability indicated with lower
      fractional volume retrieved. Islet-containing smaller-size microcapsules made of
      high-M alginate were more stable and had less cellular attachment compared with
      the regular-size capsules, although the normoglycemic period was comparable
      between two groups of rats receiving transplants with smaller-size microcapsules
      (48+/-8 days, n=8) or regular-size capsules (59+/-11 days, n=4) in allogeneic
      experiments. In syngeneic experiments, all of the rats (n=4) maintained
      normoglycemia up to 210 days after transplantation. CONCLUSION: These results
      indicate that regular-size alginate capsules do less well in rats than in our
      previous experiments with mice. Smaller capsules made of alginate cross-linked
      with barium appear to provide better stability and may be a useful strategy for
      use in larger recipients.

PMID- 15714170
TI  - Tuberculosis in lung transplant recipients.
AB  - BACKGROUND: Post-lung transplant infection is one of the leading causes of
      morbidity and mortality. The cause and incidence are similar in many series;
      however, infections such as Mycobacterium tuberculosis are influenced by the
      epidemiologic situation. The authors present a prospective and observational
      study to define the incidence, clinical presentation, and course of tuberculosis
      in a cohort of lung transplant patients at a single center in Spain. METHODS:
      Between 1990 and 2002, cutaneous delayed-type hypersensitivity testing and
      pathologic and microbiologic study of explanted lungs were conducted in 187 lung
      transplant patients. Serial bronchoscopies with transbronchial biopsy and
      bronchioalveolar lavage were performed during follow-up. The diagnosis of
      tuberculosis was established only when M. tuberculosis was identified in any
      sample or when histopathologic study was conclusive. RESULTS: Forty-eight
      patients were classified as anergic (25.6%) and 61 (32.6%) were classified as
      having a positive tuberculin skin test. Of the 109 patients, 95 received latent
      tuberculosis infection prophylaxis. Tuberculosis was diagnosed in 12 patients
      (6.41%); in six of them, diagnosis was determined from the explanted lungs. The
      remainder were diagnosed during follow-up. Fever and dyspnea were the most common
      symptoms. Chest radiographic findings presented an alveolar pattern. All patients
      responded well to antituberculous therapy; no deaths were attributable to
      tuberculosis. CONCLUSIONS: In the authors' experience, tuberculosis is not rare
      in lung transplant patients and can be managed successfully with antituberculous
      therapy without rifampin. A systematic protocol for diagnosing tuberculosis of
      the explanted lung is useful for reducing tuberculous complications of the
      implanted lung.

PMID- 15714172
TI  - Switching from cyclosporine to tacrolimus in patients with chronic transplant
      dysfunction or cyclosporine-induced adverse events.
AB  - BACKGROUND: Progressive renal-function decline caused by chronic allograft
      nephropathy is the main cause of long-term failure after kidney transplantation.
      Moreover, chronic cyclosporine (CsA)-induced nephrotoxicity is an important
      nonimmunologic factor contributing to graft dysfunction and loss, and adverse
      events may require CsA withdrawal. METHODS: Tacrolimus (Tac) replaced CsA-based
      immunosuppression in 133 transplant patients (114 kidney, 15 kidney-pancreas, 4
      pancreas after kidney) with progressive loss of renal function (71% of patients)
      or CsA intolerance (29% of patients) not responding to CsA dose-lowering. The
      primary end-points of this prospective study focusing on renal function were the
      safety and efficacy of Tac immunosuppression. RESULTS: Tac was generally well
      tolerated but definitively withdrawn for 23 (17%) patients (21 graft failures, 1
      case of diabetes, and 1 case of clinical intolerance). Differential creatinemia
      (creatinemia-nadir creatinemia after transplantation) decreased significantly
      from 85.4+/-9.8 to 39.0+/-7.5 mumol/L (P<0.001; mean+/-SEM) after 1 year and
      3.6+/-18.1 mumol/L (P<0.01) after 4 years. For patients with CsA intolerance,
      switch to Tac improved intolerance symptoms in all cases. Blood urea, creatinine
      clearance, blood total cholesterol, and triglycerides improved significantly, and
      the percentage of hypertensive patients remained stable with no de novo
      hypertension. During follow-up, one patient experienced an acute rejection
      episode (not histologically proven), and four died. Twenty-one (16%) transplants
      failed, significantly more frequently in patients with advanced renal impairment
      before Tac (P<0.0001). CONCLUSION: Switching from CsA to Tac can be an
      alternative strategy in kidney-transplant patients suffering from chronic
      allograft dysfunction or CsA toxicity. The persistently improved renal function
      over several months of evaluation suggests that in these patients, Tac might be
      less nephrotoxic than CsA and could prolong transplant function despite CsA
      failure.

PMID- 15714171
TI  - Comparison of low and high initial tacrolimus dosing in primary heart transplant
      recipients: a prospective European multicenter study.
AB  - BACKGROUND: The purpose of this prospective, randomized, open-label, phase II,
      multicenter study was to optimize the initial oral dose of tacrolimus. METHODS: A
      total of 113 patients were randomly assigned to initial low-dose (0.075
      mg/kg/day, n=55) or high-dose (0.15 mg/kg/day, n=58) oral tacrolimus and followed
      for 3 months. Target whole-blood trough levels were 10 to 20 ng/mL. Prophylactic
      use of corticosteroids and azathioprine was identical in both groups, and
      antibody induction was mandatory. The primary endpoint was the time to and
      incidence of the initial oral tacrolimus dose adjustment because of toxicity or
      rejection, or withdrawal before initial dose change. Efficacy was assessed by the
      occurrence of biopsy-proven rejection (International Society for Heart and Lung
      Transplantation grade > or =1B). RESULTS: In the primary endpoint, no significant
      difference was observed between the low- and high-dose groups. After 3 months,
      there was no difference in freedom from initial oral tacrolimus dose change
      because of rejection, toxicity, or withdrawal (89.0% vs. 87.6%; not significant
      [NS]). In both groups, dose adjustments were mainly required to achieve and
      maintain target blood levels (80.0% vs. 82.8%; NS). Patient survival was 92.7%
      and 98.3% (NS). There was no significant difference between groups regarding
      freedom from biopsy-proven acute rejection (57.1% vs. 66.3%; NS). The overall
      safety profiles indicated a tendency toward better tolerability in the low-dose
      group. CONCLUSIONS: Although low-dose and high-dose tacrolimus had similar
      efficacy, low-dose tacrolimus was associated with a more favorable safety
      profile. Therefore we recommend starting tacrolimus therapy after antibody
      induction at 0.075 mg/kg and adjust dose according to whole-blood trough levels.

PMID- 15714173
TI  - Simultaneous development of lymphoma in recipients of renal transplants from a
      single donor: donor origin confirmed by human leukocyte antigen staining and
      microsatellite analysis.
AB  - BACKGROUND: Posttransplant lymphoproliferative disorders (PTLD) occur in 0.5% to
      2.5% of cases in renal-transplant recipients. Epstein-Barr virus (EBV) is usually
      detected in the tumor cells, suggesting a role for this virus as an agent of B
      cell proliferation. It is unusual for patients receiving allografts from the same
      donor to develop PTLD simultaneously. METHODS: we describe two patients who
      received renal allografts from the same donor and developed PTLD simultaneously.
      The presence of EBV in both tumors was confirmed. In this report, the origin of
      tumor cells was determined by immunohistochemical human leukocyte antigen (HLA)
      typing and microsatellite analysis. Clonality was studied by immunoglobulin gene
      rearrangement analysis. RESULTS: Our results suggest that the tumor originated
      from donor cells in both patients but, because immunoglobulin gene rearrangements
      were different, this could mean that lymphoid cells proliferate independently in
      each recipient. CONCLUSIONS: We propose the following pathogenesis:
      immortalization of passenger B lymphocytes by EBV, proliferation of these cells,
      and development of PTLD by means of immunosuppression, antigenic stimulation, and
      HLA mismatch.

PMID- 15714174
TI  - Efficacy of valganciclovir administered as preemptive therapy for cytomegalovirus
      disease in liver transplant recipients: impact on viral load and late-onset
      cytomegalovirus disease.
AB  - BACKGROUND: The efficacy of valganciclovir used as preemptive therapy for
      cytomegalovirus (CMV) disease in liver transplant recipients is not known.
      METHODS: Between 1996 and 2004, surveillance testing using CMV antigenemia was
      performed at weeks 2, 4, 6, 8, 10, 12, and 16 posttransplant. A total of 28.8%
      (17/59) of the patients from 2001 to 2004 with antigenemia who received
      valganciclovir as preemptive therapy were compared with 26.2% (21/80) of the
      patients from 1996 to 2000 who received oral ganciclovir as preemptive therapy.
      RESULTS: The mean decline in the antigenemia level after initiation of
      valganciclovir and oral ganciclovir was 80.5% versus 50.7% at 1 week, 99.5%
      versus 89.4% at 2 weeks, and 100% versus 97.7% at 4 weeks, respectively. A higher
      proportion of patients who received valganciclovir (64.7%) belonged to the high
      risk group (R-/D+) than patients who received oral ganciclovir (33.3%, P=0.10).
      Recurrent shedding was documented in 47.1% (8/17) of the patients in the
      valganciclovir group and 28.6% (6/21) of the patients in the oral ganciclovir
      group (P>0.20). Recurrent shedding correlated significantly with R-/D+ CMV
      serostatus and baseline CMV antigenemia level, regardless of the study group. No
      patient in either group developed CMV disease during or after the period of
      surveillance monitoring. The incidence of opportunistic infections and patient
      outcome did not differ for the valganciclovir group versus the oral ganciclovir
      group or patients without CMV infection (P>0.20). CONCLUSION: Antigenemia
      directed valganciclovir as preemptive therapy seems to be effective for the
      prevention of CMV disease in liver transplant recipients, including high-risk
      patients.

PMID- 15714175
TI  - Assessment of a novel two-component enzyme preparation for human islet isolation
      and transplantation.
AB  - BACKGROUND: Biologic characteristics of enzyme products used for islet isolation
      are critical for the success of islet transplantation. In particular, lot-to-lot
      variability significantly affects the yields of the isolation procedure. In this
      study, we have evaluated a new enzyme preparation in which highly purified
      collagenase can be blended with separately supplied neutral protease in a
      predetermined ratio. METHODS: We compared the results of human-islet isolations
      performed either with Collagenase NB1 supplemented with Neutral Protease NB
      (group I, n=9) or with Liberase (group II, n=9). RESULTS: Endotoxin contents of
      the enzyme preparations were lower in group I. Total islet yields were similar in
      both groups, but islet equivalents per gram of pancreas was higher in group I
      (4,020+/-1,240 vs. 2,360+/-1,350; P<0.05). Islet morphology was improved in group
      I with significantly higher proportion of free and intact islets (71+/-9% vs.
      52+/-14%; P<0.01). In vitro function was improved and apoptosis rate was lower in
      group I. CONCLUSIONS: This new enzyme blend was as efficient as Liberase in terms
      of islet yields and showed improvements in islet morphology, viability, and in
      vitro function. The possibility to control lot-to-lot variability and the low
      endotoxin contents make Collagenase NB1 a promising product for human-islet
      isolation.

PMID- 15714176
TI  - V(H)3 and V(H)6 immunoglobulin M repertoire reconstitution after hematopoietic
      stem-cell transplantation in children.
AB  - BACKGROUND: Immune reconstitution after hematopoietic stem-cell transplantation
      (HSCT) occurs gradually. Thus, a variable period of immunodeficiency may be
      present, leading to immunomediated complications, such as graft-versus-host
      disease (GVHD) and opportunistic infections. METHODS: To better understand the
      kinetics of B-cell repertoire reconstitution in children, 49 pediatric patients
      were analyzed before and after transplantation by immunoglobulin (Ig) HCDR3
      fingerprinting, which is a molecular technique that analyzes one of the
      hypervariable segments of the Ig heavy chain, which provides the amino acid
      residues that are essential to interact with antigens. RESULTS: In healthy
      donors, the CDR3 fingerprinting profile shows 16 to 20 bands, and each band
      corresponds to a particular length of CDR3. This situation is considered
      polyclonal. Patients analyzed just after transplantation show strong
      oligoclonality, because only a few CDR3 bands are detected within the first 3 to
      6 months. CONCLUSIONS: The authors' data show a significant lag in
      diversification of the B-cell repertoire, which reaches the polyclonal situation
      of normal healthy donors approximately 6 months after HSCT. This period may vary
      depending on the type of transplant (autologous vs. allogeneic) and on the
      immunosuppressive therapy related to GVHD.

PMID- 15714177
TI  - A controlled study of vitamin D3 to prevent bone loss in renal-transplant
      patients receiving low doses of steroids.
AB  - BACKGROUND: New and potent immunosuppressive regimens allow for reduced doses of
      corticosteroids after renal transplantation. The aims of our study were to
      investigate whether the use of low-dose corticosteroids is associated with a
      reduction in posttransplant bone loss and to assess the ability of
      cholecalciferol supplementation to further decrease bone loss in this setting.
      METHODS: Ninety patients admitted for renal transplantation and scheduled to be
      treated per protocol with low doses of prednisolone were randomized to receive
      either 400 mg daily oral calcium (Ca group, n=44) or the same dose of calcium in
      association with a monthly dose of 25,000 IU of vitamin D3 (CaVitD group, n=46).
      Bone mineral density (BMD) was measured by dual energy absorptiometry at baseline
      and at 1 year. RESULTS: The overall population experienced a moderate but
      significant -2.3+/-0.9% loss of lumbar spine BMD (P<0.01) but no bone loss at the
      femoral neck and shaft during the first posttransplant year. Bone loss tended to
      be slightly higher in the CaVitD group, but the difference did not reach
      statistical significance. Patients in the CaVitD group had significantly higher
      25(OH) but not 1,25(OH)2 vitamin D levels. We observed a highly significant
      negative correlation between 25(OH) vitamin D and intact parathyroid hormone
      (iPTH) serum levels. CONCLUSIONS: Kidney-transplant recipients receiving modern
      immunosuppressive regimens with low doses of corticosteroids experience only
      minimal loss of BMD during the first posttransplant year. Cholecalciferol
      supplementation did not prevent posttransplant bone loss but contributed to the
      normalization of iPTH levels after renal transplantation.

PMID- 15714178
TI  - Effect of leflunomide and cidofovir on replication of BK virus in an in vitro
      culture system.
AB  - BACKGROUND: Cidofovir and Leflunomide are used empirically in the treatment of BK
      virus nephropathy. The aim of this study is to quantify the antiviral activity of
      these drugs. METHODS: BK virus was grown in a cell-culture system. The rate of
      viral replication in the presence or absence of the drug being tested was
      assessed using a quantitative polymerase chain reaction assay. RESULTS: The
      inhibitory concentration, effective concentration, and selectivity index for
      Leflunomide are 39.7+/-6.9, 11.3+/-2.8, and 3.8+/-0.8 microg/mL, respectively.
      For Cidofovir, these indices were, respectively, 63.9+/-17.2, 36.3+/-11.7, and
      2.3+/-0.8 microg/mL. CONCLUSIONS: The in vitro activity of Cidofovir and
      Leflunomide is modest, and the selectivity index is low. There is a need to
      develop more effective and less toxic anti-BK virus drugs for clinical use.

PMID- 15714179
TI  - Calcineurin inhibitors and proximal renal tubular injury in renal transplant
      patients with proteinuria and chronic allograft nephropathy.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) is commonly associated with
      proteinuria. In native nephropathies, proteinuria is linked with proximal renal
      tubular damage. This study uses regression analysis to link proteinuria with
      urinary N-acetyl-beta-d-glucosaminidase (NAG) as a marker of tubular injury or
      hyperfunction in renal transplant patients. METHODS: Proteinuria and urinary NAG
      were measured and regression analysis applied in 105 transplant patients (42 with
      CAN). Most were receiving calcineurin inhibitor-based immunosuppression
      (cyclosporine, n=60; tacrolimus, n=26; and neither drug, n=19). Patients with
      native nephropathies (n=96) and volunteers (n=21) were also studied. RESULTS:
      Urinary NAG increased with increasing proteinuria. However, patients taking
      calcineurin inhibitors had higher urinary NAG at any level of urinary protein
      than those on alternative therapy, or in native nephropathies. CONCLUSIONS: In
      groups of transplant patients taking different immunosuppressive regimens,
      regression analysis of urinary NAG against urinary protein can identify the
      separate effects of drug-related tubular injury or hyperfunction from that of
      proteinuria.

PMID- 15714181
TI  - Epidural anesthesia for orthopedic surgery: what are the (presumed) benefits?

PMID- 15714180
TI  - Photopheresis for the treatment of refractory renal graft rejection.
AB  - Acute rejection episodes still occur after kidney transplantation in spite of
      modern immunosuppressive protocols including combined tacrolimus, mycophenolate
      mofetil, and prednisolone. The authors present seven cases of biopsy-proven acute
      rejection after kidney transplantation refractory to conventional rejection
      therapy with repeated pulses of high-dose steroids followed by polyclonal or
      monoclonal antibodies that responded well to photopheresis treatment.
      Photopheresis is an atoxic immunomodulatory apheresis-based treatment with no
      generalized immunosuppressive action; rather, it is directed at suppressing donor
      specific T-cell clones. At the last follow-up, 9 to 43 months after
      transplantation, all patients had functioning grafts, with serum creatinine
      levels ranging from 105 to 312 microM. The authors conclude that photopheresis
      treatment contributed to the favorable outcome. Therefore, the authors are
      presently designing a prospective, randomized trial to evaluate the effect of
      photopheresis as an adjuvant prophylactic treatment after renal transplantation.

PMID- 15714182
TI  - Review of local anaesthetic agents.
AB  - The currently available local anaesthetic agents are capable of providing high
      quality nerve blockade in a wide variety of clinical circumstances. Our
      understanding of the mechanisms and consequences of toxicity is increasing
      rapidly. Knowledge of the chemistry of local anaesthetics has enabled clinicians
      to exploit the increased safety of single isomer agents. However, the extent, if
      any, of this improvement in toxicity has yet to be proven. Established toxicity
      may be very difficult to treat and no specific reversing therapy is yet
      available. Until this occurs it is essential that practitioners of regional
      anaesthesia maintain their knowledge base and skill in techniques of
      administration of local anaesthetic, are able to recognise impending disaster,
      and constantly update their skills in resuscitation.

PMID- 15714183
TI  - Haemodynamic modifications after unilateral subarachnoid anaesthesia evaluated
      with transthoracic echocardiography.
AB  - AIM: The aim of the study is the evaluation through transthoracic
      echocardiography of the haemodynamic modifications due to unilateral subarachnoid
      anaesthesia with bupivacaine 0.5% given for orthopaedic surgery. METHODS: In this
      prospective study, at the University Hospital Orthopedics surgical theater, 20
      patients underwent orthopaedic surgery on the lower limbs. Unilateral spinal
      block was performed with hyperbaric bupivacaine 0.5%, 8 mg after a fluid
      challenge with saline solution 0.9%. Transthoracic echocardiography was performed
      and cardiac output was calculated from the left ventricular outflow tract (LVOT)
      with a recently validated technique. Cardiac output, stroke volume, ejection
      fraction, heart rate, mean arterial pressure were evaluated. These parameters
      were obtained before anaesthesia (t1), 5 minutes after anaesthesia (t2) and 16
      minutes after anaesthesia (t3). RESULTS: Systolic, mean and diastolic arterial
      pressures after 5 min and 16 min from anaesthesia significantly decreased if
      compared to basal time (p<0.05 and p<0.001 respectively) while cardiac index
      (p<0.001) and ejection fraction (p<0.05) decreased only after 16 min from
      subarachnoid anaesthesia. CONCLUSION: Despite the fluid challenge we can not
      prevent a significant fall in the blood pressure and a decrease of the left
      ventricular function calculated with the decrease of cardiac output and of the
      left ventricular ejection fraction.

PMID- 15714184
TI  - Subarachnoid sufentanil as sole agent vs standard spinal bupivacaine in
      transurethral resection of the bladder.
AB  - AIM: The aim of the study was to determine whether intrathecal sufentanil alone
      provides an adequate analgesia for patients undergoing transurethral resection of
      the bladder (TURB) and to compare it to standard spinal bupivacaine anesthesia in
      terms of motor and sensory blockade, discharge time and side effects. METHODS:
      Sixty-two patients were blindly and randomly assigned to receive either
      intrathecal bupivacaine (10 mg of 0.5% hyperbaric bupivacaine) or intrathecal
      sufentanil (15 microg). Motor and sensory blockade was evaluated using a modified
      Bromage scale as well as cold and pinprick tests. Severity of pain was assessed
      by means of a 10-point verbal analog scale. RESULTS: We found that the mean
      duration of sensory blockade was similar for both sufentanil and bupivacaine
      patients but the quality of analgesia induced by sufentanil alone was poor as
      compared with spinal bupivacaine anesthesia. CONCLUSION: The subarachnoid
      administration of sufentanil 15 mg seems to be inadequate for TURB surgery. In
      addition, the advantage of a faster recovery we observed in sufentanil patients
      is minimized by the occurrence of a troublesome symptom such as pruritus. On the
      other hand, spinal bupivacaine produces an undesirable motor blockade exceeding,
      in our opinion, the requirement for TURB procedure.

PMID- 15714185
TI  - 0.2% ropivacaine with or without sufentanil for patient-controlled epidural
      analgesia after anterior cruciate ligament repair.
AB  - AIM: The aim of this prospective, randomized, double-blind study was to evaluate
      the effects of adding 0.5 microg/ml sufentanil to 0.2% ropivacaine for patient
      controlled epidural analgesia (PCEA) on the quality of postoperative pain control
      in patients undergoing anterior cruciate ligament (ACL) reconstruction. METHODS:
      Twenty ASA physical status I-II patients, scheduled to have elective ACL repair
      were studied. Combined spinal-epidural anesthesia was performed at the L3-L4 or
      L4-L5 interspace using a needle-through-needle technique. Spinal anesthesia was
      induced with 10 mg of 0.5% hyperbaric bupivacaine. Postoperative epidural
      analgesia was started at the end of surgery using a continuous epidural infusion
      of 0.2% ropivacaine alone (n=10) or 0.2% ropivacaine/0.5 mg mL(-1) sufentanil
      (n=10). The degree of pain was evaluated at 1, 8, 16, 24 and 48 hours after
      surgery; at the same observation times the degree of motor block, sedation,
      oxygen saturation, total consumption of PCEA solution and incremental doses given
      to the patient were also recorded. RESULTS: No differences in the quality of
      intraoperative anesthesia was observed, and in no case general anesthesia was
      required to complete surgery. Patients receiving the combination of ropivacaine
      and sufentanil showed lower levels of VAS from 16 hours after surgery as compared
      with ropivacaine group (P=0.02). However, no differences in the degree of pain
      were observed between the 2 groups during continuous passive mobilization.
      CONCLUSION: Adding 0.5 microg/ml sufentanil to 0.2% ropivacaine for patient
      controlled epidural analgesia improved pain control at rest but did not result in
      significant improvement of postoperative analgesia during continuous passive
      mobilization.

PMID- 15714186
TI  - Conscious sedation during endoscopic retrograde colangiopancreatography:
      implementation of SIED-SIAARTI-ANOTE guidelines in Belluno Hospital.
AB  - AIM: In this study we describe the results of adoption of local guidelines for
      conscious sedation (CS) during endoscopic-retrograde-cholangiopancreatography
      (ERCP) in Belluno Hospital. Local guidelines were created referring to SIED
      SIAARTI-ANOTE guidelines for CS in gastrointestinal endoscopy. METHODS: Between
      January 2002 and February 2004, 300 ERCPs to be performed under CS have been
      scheduled. According to local guidelines CS was performed by the
      gastroenterologist assisted by an anesthesia nurse. An anesthesiologist was
      always on call in the intensive care unit (ICU) for emergencies and could be on
      the site in less than 5 min. RESULTS: In 278 patients the procedure was performed
      safely and effectively by the gastroenterologist without any anesthesiological
      assistance. At follow-up controls patients had either positive or no recollection
      of the procedure. An anesthesiologist was called in 13 cases to perform deep
      sedation and in 9 cases to deal with undesired effects (arterial hypertension in
      5 patients, 1 episode of bradycardia, 1 of ventricular tachycardia, 1 of atrial
      fibrillation and 1 of hypoxia). CONCLUSION: In our experience, CS during ERCP can
      be safely performed autonomously by a gastroenterologist in the majority of
      cases. Drug prescription protocol and the presence of an anesthesia nurse create
      ideal conditions for the operator, patient comfort and good results with a low
      incidence of undesired events and few calls for the anesthesiologist. To allow
      safe and effective performance of CS, the Department of Anesthesia should promote
      the in-service training and up dating of gastroenterologists and anesthesia
      nurses.

PMID- 15714187
TI  - Co-occurrence of DSM-IV personality disorders in the United States: results from
      the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - The objective of this study was to determine the co-occurrence of 7 of the 10
      Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision ( DSM-IV-TR ) personality disorders (PDs) in the US population. Face-to
      face interviews were conducted with 43 093 respondents in the National Institute
      on Alcohol Abuse and Alcoholism's 2001-2002 National Epidemiologic Survey on
      Alcohol and Related Conditions, a nationally representative survey of the US
      population. Odds ratios were calculated to determine associations among PDs. All
      associations among PDs were positive and statistically significant. PDs were
      significantly associated with other PDs within the same cluster, in addition to
      being highly associated with PDs of other DSM-IV PD clusters. Co-occurrence
      between DSM-IV PDs is pervasive in the US general population. Future research is
      needed on the creation of dimensional representations of DSM-IV PDs as an adjunct
      to categorical diagnoses.

PMID- 15714188
TI  - The spectrum of substance use in mood and anxiety disorders.
AB  - This study evaluates the prevalence of threshold and subthreshold use of
      substances among patients with psychiatric disorders and 2 comparison groups.
      Participants were outpatients and inpatients with mood and anxiety disorders,
      subjects with opiate dependence, and a comparison group of individuals not
      undergoing treatment for psychiatric disorders. Assessments included the
      Structured Clinical Interview for Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition , Axis I Disorders, an interview exploring the spectrum
      of substance use (Structured Clinical Interview for the Spectrum of Substance
      Use), and a self-report instrument exploring the spectrum of 5 psychiatric
      disorders (General 5-Spectrum Measure). The overall frequency of substance use
      disorder (SUD) and that of subthreshold use were 46% and 8% in patients with
      bipolar disorder, 4% and 26% in those with panic disorder, 8% and 26% in those
      with obsessive-compulsive disorder, and 6% and 10% in the control group,
      respectively ( Idouble dagger 2 = 51.6, P < .001). Inspection of standardized
      residuals indicated that alcohol use disorder and SUD were significantly ( P <
      .05) more frequent in subjects with bipolar disorder than among those with
      obsessive-compulsive disorder or panic disorder. The latter showed a
      significantly higher subthreshold use of substances than control subjects. The
      pattern of motivations for use varied according to the psychiatric disorder. Our
      results suggest that the well-established relationship between SUDs and
      psychiatric disorders might be the end point of a process that starts from
      increased proneness to substance use, which first leads to self-medication and
      then may eventually develop into substance abuse or dependence, among subjects
      with psychiatric symptoms.

PMID- 15714189
TI  - Cluster analysis of obsessive-compulsive spectrum disorders in patients with
      obsessive-compulsive disorder: clinical and genetic correlates.
AB  - BACKGROUND: Comorbidity of certain obsessive-compulsive spectrum disorders
      (OCSDs; such as Tourette's disorder) in obsessive-compulsive disorder (OCD) may
      serve to define important OCD subtypes characterized by differing phenomenology
      and neurobiological mechanisms. Comorbidity of the putative OCSDs in OCD has,
      however, not often been systematically investigated. METHODS: The Structured
      Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition , Axis I Disorders-Patient Version as well as a Structured
      Clinical Interview for Putative OCSDs (SCID-OCSD) were administered to 210 adult
      patients with OCD (N = 210, 102 men and 108 women; mean age, 35.7 +/- 13.3). A
      subset of Caucasian subjects (with OCD, n = 171; control subjects, n = 168),
      including subjects from the genetically homogeneous Afrikaner population (with
      OCD, n = 77; control subjects, n = 144), was genotyped for polymorphisms in genes
      involved in monoamine function. Because the items of the SCID-OCSD are binary
      (present/absent), a cluster analysis (Ward's method) using the items of SCID-OCSD
      was conducted. The association of identified clusters with demographic variables
      (age, gender), clinical variables (age of onset, obsessive-compulsive symptom
      severity and dimensions, level of insight, temperament/character, treatment
      response), and monoaminergic genotypes was examined. RESULTS: Cluster analysis of
      the OCSDs in our sample of patients with OCD identified 3 separate clusters at a
      1.1 linkage distance level. The 3 clusters were named as follows: (1) "reward
      deficiency" (including trichotillomania, Tourette's disorder, pathological
      gambling, and hypersexual disorder), (2) "impulsivity" (including compulsive
      shopping, kleptomania, eating disorders, self-injury, and intermittent explosive
      disorder), and (3) "somatic" (including body dysmorphic disorder and
      hypochondriasis). Several significant associations were found between cluster
      scores and other variables; for example, cluster I scores were associated with
      earlier age of onset of OCD and the presence of tics, cluster II scores were
      associated with female gender and childhood emotional abuse, and cluster III
      scores were associated with less insight and with somatic obsessions and
      compulsions. However, none of these clusters were associated with any particular
      genetic variant. CONCLUSION: Analysis of comorbid OCSDs in OCD suggested that
      these lie on a number of different dimensions. These dimensions are partially
      consistent with previous theoretical approaches taken toward classifying OCD
      spectrum disorders. The lack of genetic validation of these clusters in the
      present study may indicate the involvement of other, as yet untested, genes.
      Further genetic and cluster analyses of comorbid OCSDs in OCD may ultimately
      contribute to a better delineation of OCD endophenotypes.

PMID- 15714190
TI  - Comorbid personality disorders in subjects with panic disorder: do personality
      disorders increase clinical severity?
AB  - Personality disorders are common in subjects with panic disorder. Personality
      disorders have been shown to affect the course of panic disorder. The purpose of
      this study was to examine which personality disorders affect clinical severity in
      subjects with panic disorder. This study included 122 adults (71 women, 41 men)
      who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (
      DSM-IV ) criteria for panic disorder (with or without agoraphobia). Clinical
      assessment was conducted by using the Structured Clinical Interview for DSM-IV
      Axis I Disorders, the Structured Clinical Interview for DSM-IV Axis II
      Personality Disorders, and the Panic and Agoraphobia Scale, Global Assessment
      Functioning Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory.
      Patients who had a history of sexual abuse were assessed with Sexual Abuse
      Severity Scale. Logistic regressions were used to identify predictors of suicide
      attempts, suicidal ideation, sexual abuse, and early onset of disorder. The rates
      of comorbid Axes I and II psychiatric disorders were 80.3% and 33.9%,
      respectively, in patients with panic disorder. Patients with panic disorder with
      comorbid personality disorders had more severe anxiety, depression, and
      agoraphobia symptoms, had earlier ages at onset, and had lower levels of
      functioning. The rates of suicidal ideation and suicide attempts were 34.8% and
      9.8%, respectively, in subjects with panic disorder. The rate of patients with
      panic disorder and a history of childhood sexual abuse was 12.5%. The predictor
      of sexual abuse was borderline personality disorder. The predictors of suicide
      attempt were comorbid paranoid and borderline personality disorders, and the
      predictors of suicidal ideation were comorbid major depression and avoidant
      personality disorder in subjects with panic disorder. In conclusion, this study
      documents that comorbid personality disorders increase the clinical severity of
      panic disorder. Borderline personality disorder may be the predictor of a history
      of sexual abuse and early onset in patients with panic disorder. Paranoid and
      borderline personality disorders may be associated with a high frequency of
      suicide attempts in patients with panic disorder.

PMID- 15714191
TI  - Employees' perspectives on ethically important aspects of genetic research
      participation: a pilot study.
AB  - PURPOSE: Insights from genetic research may greatly improve our understanding of
      physical and mental illnesses and assist in the prevention of disease. Early
      experience with genetic information suggests that it may lead to stigma,
      discrimination, and other psychosocial harms, however, and this may be
      particularly salient in some settings, such as the workplace. Despite the
      importance of these issues, little is known about how healthy adults, including
      workers, perceive and understand ethically important issues in genetic research
      pertaining to physical and mental illness. METHOD: We developed, pilot tested,
      and administered a written survey and structured interview to 63 healthy working
      adults in 2 settings. For this paper, we analyzed a subset of items that assessed
      attitudes toward ethically relevant issues related to participation in genetic
      research on physical and mental illness, such as its perceived importance, its
      acceptability for various populations, and appropriate motivations for
      participation. RESULTS: Our respondents strongly endorsed the importance of
      physical and mental illness genetic research. They viewed participation as
      somewhat to very acceptable for all 12 special population groups we asked about,
      including persons with mental illness. They perceived more positives than
      negatives in genetic research participation, giving neutral responses regarding
      potential risks. They affirmed many motivations for participation to varying
      degrees. Men tended to affirm genetic research participation importance,
      acceptability, and motivations more strongly than women. CONCLUSION: Healthy
      working persons may be willing partners in genetic research related to physical
      and mental illnesses in coming years. This project suggests the feasibility and
      value of evidence-based ethics inquiry, although further study is necessary.
      Evidence regarding stakeholders' perspectives on ethically important issues in
      science may help in the development of research practices and policy.

PMID- 15714192
TI  - Quality of life in kleptomania and pathological gambling.
AB  - The current study was constructed to examine the similarities and differences in
      the quality of life of patients with kleptomania and pathological gambling (PG).
      Thirty patients with kleptomania, 43 with PG, and 30 normal control subjects were
      assessed with the Quality of Life Inventory that assesses self-reported
      satisfaction with life. Both patients with kleptomania and PG had significantly
      lower quality of life scores than normal control subjects ( t = 7.32; df = 58; P
      < .001; t = 7.32; df = 71; P < .001, respectively). These results suggest that
      patients with kleptomania and pathological gamblers have notably poor quality of
      life.

PMID- 15714193
TI  - Sensitivity of ICD-10 diagnosis of psychotic disorders in the Israeli National
      Hospitalization Registry compared with RDC diagnoses based on SADS-L.
AB  - OBJECTIVE: The Israeli National Psychiatric Hospitalization Registry is a
      nationwide list of all psychiatric hospitalizations in the country and has been
      widely used as a source of data for psychiatric research. This study assessed the
      sensitivity of the diagnosis of psychotic disorders ( International Statistical
      Classification of Diseases, 10th Revision [ ICD-10 ] F20.0-F29.9) and
      schizophrenia ( ICD-10 F20.0-F20.9) in the Registry. METHOD: Registry discharge
      diagnoses of psychotic disorders ( ICD-10 F20.0-F29.9) and schizophrenia ( ICD-10
      F20.0-F20.9) were compared with research diagnoses derived from best-estimate
      procedures based on Research Diagnostic Criteria (RDC) using structured clinical
      research interviews, hospital records, and family information. RESULTS: Out of
      169 patients meeting RDC for psychotic disorder, 150 also had a diagnosis of
      psychotic disorders in the Registry, yielding a sensitivity of 0.89. Re-running
      this analysis for the narrow definition of schizophrenia identified 94 patients
      who were diagnosed with schizophrenia using RDC; 82 of those patients also had a
      diagnosis of schizophrenia in the Registry, yielding a sensitivity of 0.87.
      CONCLUSION: In 87% to 89% of cases with psychotic disorders or with
      schizophrenia, Registry diagnoses agreed with RDC diagnoses, a rate of agreement
      comparable with those of other, similar registries. Because a large number of
      analyses derived from this and similar national registries will be published in
      the coming years, this constitutes relevant information.

PMID- 15714194
TI  - Impulsive disorders in Japanese adult patients with obsessive-compulsive
      disorder.
AB  - In this study, we sought to characterize obsessive-compulsive disorder (OCD)
      patients with impulsive features, and to determine whether they constitute a
      distinct subtype of OCD. Therefore we systematically assessed impulse control
      disorders and other impulsive conditions categorized as obsessive-compulsive
      spectrum disorders (OCSDs) in 153 Japanese adult patients with OCD. Forty-five
      subjects (29%) had concurrent impulsive disorders, and they were differentiated
      from other OCD patients on a range of demographic features (e.g., younger age at
      onset), and clinical features (e.g., pervasive and severe psychopathology, and
      poor treatment outcome). However, on logistic regression, none of these variables
      predicted comorbid impulsivity. The findings appear to support the argument that
      OCD patients with impulsive features constitute a subtype of OCD. However,
      further research is necessary to determine whether impulsivity should be
      conceptualized as lying on a spectrum with compulsivity or as a dimension that is
      orthogonal to compulsivity.

PMID- 15714195
TI  - The contribution of temperament and character to schizotypy multidimensionality.
AB  - Schizotypy could be viewed either as an underlying "personality organization"
      that includes the "liability" to schizophrenia, i.e., as a hypothetical latent
      construct, or it could be referred to the phenotypic manifestations of a
      particular personality organization. The psychobiologic model of the structure of
      personality accounts for dimensions of both temperament and character. This study
      examined the covariances between Temperament and Character Inventory (TCI) scores
      and aspects of Schizotypal Personality Questionnaire (SPQ) scores in a
      nonclinical sample. The results showed the relationship between the number of
      schizotypal phenotypic traits, as quantified by SPQ measures, and a specific
      configuration of character, namely, high self-transcendence (ST), low self
      directedness (SD), and low cooperativeness (C). Data suggested that the unique
      combination of high ST, low SD, and low C seems to lead to a special risk for
      schizotypy. In particular, ST is a predictor either of psychosis proneness or
      mature, effective adapted and self-satisfied personalities, depending on its
      interaction with other TCI dimensions, both temperament and character.

PMID- 15714196
TI  - Human personality traits are associated with individual environmental traits in
      male adolescents--a pilot study.
AB  - The human personality seems to be formed by biological (internal) and
      environmental (external) factors, which function interactively. This pilot study
      examined the relationship between fundamental personality traits and individual
      environmental traits in healthy adolescents. A complex relationship between
      personality traits and candidate environmental traits was found in this sample.
      Parental smoking, one of the hypothetical environmental traits, was significantly
      associated with the sociability personality trait of adolescent offspring.
      Another hypothetical environmental trait-parent/child attachment status-"was
      related to novelty-seeking personality. Unexpectedly, these associations were
      observed only in male but not in female adolescents. The present study suggested
      that (1) parental smoking behavior might directly or indirectly affect offspring
      social behavior and related personality by nongenetic transmission; (2) past and
      present data indicated that the triad of a poor parent/child relationship,
      novelty-seeking personality, and risky/delinquent behavior is closely connected.
      Investigations of environmental traits at a nonclinical level may lead us to
      understand the overall human personality, as with research on genes and
      biological traits that are implicated in the formation of mental activity.

PMID- 15714197
TI  - The Positive and Negative Symptoms Questionnaire: a self-report scale in
      schizophrenia.
AB  - The assessment of various symptoms in schizophrenia has received much interest,
      although few studies have compared evaluations by clinicians to those of their
      patients. Self-report tools may improve service delivery, data collection, and
      possibly also treatment adherence. We constructed the Positive and Negative
      Symptoms Questionnaire (PNS-Q), a self-report measure, after items from the Scale
      for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of
      Negative Symptoms (SANS). The PNS-Q contained 68 items and was administered to 61
      schizophrenic inpatients. We examined its psychometric properties and utility as
      a self-report tool in schizophrenia. The PNS-Q exhibited high internal
      consistency for both its positive and negative subscales. External validity with
      the SAPS and SANS was low. The positive symptoms subscale correlated
      significantly with the SAPS ( r = .341, P < .01), whereas the negative symptoms
      subscale did not correlate at all with the SANS ( r = -0.086, P > .1). The
      correlation between patients' insight and scores of the PNS-Q was mixed. A
      partial correlation analysis failed to confirm a relationship between the rating
      of the patients' level of insight (measured by the Amador Scale to Assess
      Unawareness of Mental Disorders [SUMD]) and the disparity between the PNS-Q and
      the SAPS and SANS. However, the PNS-Q correlated highly with McEvoy's Vignettes,
      a measure of self-perception of symptoms. The results of this study are discussed
      in light of current research and methodologic issues. The PNS-Q reflects
      schizophrenics' self-perception, an important, yet neglected, aspect of
      schizophrenia. Using this new measure, we believe that clinicians and researchers
      will be able to gain insight to the inner world of these patients and improve
      their condition, as well as enhance patients' involvement in treatment planning.

PMID- 15714198
TI  - Development of an inventory for measuring war-related events in refugees.
AB  - Knowledge about the range of war-related events experienced by refugees is
      lacking. This initial report of the New Mexico Refugee Project (NMRP) details the
      development of the Comprehensive Trauma Inventory (CTI), the first empirically
      developed instrument that measures war-related events in community-dwelling
      refugees. Both expert and participant methods using quantitative and qualitative
      approaches were used to broaden knowledge about the range of war-related
      experiences in refugees. The CTI-164, developed by expert rational methods, was
      administered to 36 Kurdish and 31 Vietnamese refugees along with an in-depth
      interview (IDI) and five other quantitative instruments measuring symptoms,
      impairment, and social support. Focus groups (FGs) were also conducted. Text and
      descriptive analyses, t tests, and correlations were used to analyze data.
      Refugees reported an average of 150 war-related events on the CTI-164, more than
      in other studies. IDIs and FGs revealed 123 war-related events and event types
      that were not on the CTI-164 or other measures currently used. Refugees reported
      multiple chronic symptoms and significant impairment in daily functioning. The
      CTI-164 was modestly correlated with symptoms and impairment. The definable
      number and type of war-related events endured by refugees is greater than in
      previously published research. Expert rational methods are not adequate to
      develop an instrument to define war-related events and measure their association
      with health outcomes. Participatory and qualitative methods reveal events and
      event types that have not been previously defined. The CTI warrants further
      testing after revision to incorporate items and event types determined by
      qualitative methods.

PMID- 15714199
TI  - Thinking quantitatively about transcriptional regulation.
AB  - By thinking about the chemical and physical mechanisms that are involved in the
      stepwise elongation of RNA transcripts, we can begin to understand the way that
      these mechanisms are controlled within the cell to reflect the different
      requirements for transcription that are posed by various metabolic, developmental
      and disease states. Here, we focus on the mechanistic details of the single
      nucleotide addition (or excision) cycle in the transcription process, as this is
      the level at which many regulatory mechanisms function and can be explained in
      quantitative terms.

PMID- 15714200
TI  - Do inducers of apoptosis trigger caspase-independent cell death?
AB  - Apoptotic cell death is mediated by molecular pathways that culminate in the
      activation of a family of cysteine proteases, known as the caspases, which
      orchestrate the dismantling and clearance of the dying cell. However, mounting
      evidence indicates that a cell that has been treated with an apoptotic inducer
      can also initiate a suicide programme that does not rely on caspase activation.
      Here, we present recent findings and discuss the physiological relevance of
      caspase-independent cell death.

PMID- 15714201
TI  - Gemcitabine twice weekly as a radiosensitiser for the treatment of brain
      metastases in patients with carcinoma: a phase I study.
AB  - Conventional treatment for brain metastases (BM) is whole-brain radiotherapy
      (WBRT). Efficacy is poor. It might be increased by a potent radiosensitiser such
      as gemcitabine which is believed to cross the disrupted blood-brain barrier.
      Primary objective of this study was to determine the maximum tolerated dose (MTD)
      of twice weekly gemcitabine given concurrently with WBRT. Patients with BM from
      carcinoma were included. The dose of WBRT was 30 Gys (10 daily fractions).
      Gemcitabine was given 2-4 h prior to WBRT on days 1 and 8 for the first cohort of
      patients and then on days 1, 4, 8 and 11. Starting dose was 25 mg m(-2),
      escalated by 12.5 mg m(-2) increments. At least three patients were included per
      level. Dose limiting toxicity (DLT) was defined as grade 4 haematological or
      grade > or =3 nonhaematological toxicity. A total of 25 patients were included;
      74% had a PS 1 (ECOG). In all, 23 had non-small-cell lung cancer, six colorectal,
      four breast, two renal cell and one oesophageal carcinoma. A total of 92% had
      concurrent extracranial disease. Six had single BM, 13 had two or three BM and
      six multiple. Up to 50 mg m(-2) (level 4) no DLT was observed. At 62.5 mg m(-2),
      one out of six patients developed DLT (thrombocytopenia-bleeding). The next dose
      level (75 mg m(-2)) was abandoned after grade 4 bone marrow toxicity (fatal
      neutropenic sepsis) was seen in one out of two patients. So that the dose of 50
      mg m(-2) will be taken forward for further study.

PMID- 15714202
TI  - Detection of circulating epithelial cells in the blood of patients with breast
      cancer: comparison of three techniques.
AB  - This study compares the sensitivities and specificities of three techniques for
      the detection of circulating epithelial cells in the blood of patients with
      breast cancer. The number of circulating epithelial cells present in the blood of
      40 patients with metastatic breast cancer and 20 healthy volunteers was
      determined by: immunomagnetic separation (IMS) and laser scanning cytometry
      (LSC), cell filtration and LSC and a multimarker real-time RT-PCR assay. Numbers
      of cytokeratin-positive cells identified and expression of three PCR markers were
      significantly higher in the blood of patients with breast cancer than in healthy
      volunteers. Using the upper 95% confidence interval of cells detected in controls
      to determine positive patient samples: 30% of patients with metastatic breast
      cancer were positive following cell filtration, 48% following IMS, and 60, 45 and
      35% using real-time RT-PCR for cytokeratin 19, mammaglobin and prolactin
      inducible peptide. Samples were significantly more likely to be positive for at
      least one PCR marker than by cell filtration (83 vs 30%, P<0.001) or IMS (83 vs
      48%, P<0.001). The use of a multimarker real-time RT-PCR assay was therefore
      found to be the most sensitive technique for the detection of circulating
      epithelial cells in the blood of patients with breast cancer.

PMID- 15714203
TI  - Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence
      for autocrine and paracrine actions.
AB  - Interleukin-4 (IL-4) is an immunomodulatory cytokine, which can inhibit the
      growth of tumour cells. Pancreatic cancer cells and tissues express high levels
      of IL-4 receptors. The aim of this study was to characterise the effects of IL-4
      on the growth and signalling pathways of pancreatic cancer cells. Cell growth was
      determined by cell counting and MTT assays in association with fluorescence
      activated cell sorter analysis, IL-4 expression using ELISA and real-time PCR
      techniques, and signal transduction using immunoprecipitation or immunoblot
      analysis. We now report for the first time that IL-4 significantly enhanced the
      growth of five out of six cultured pancreatic cancer cell lines in a dose
      dependent manner in association with an increased fraction of cells in S-phase.
      Surprisingly, all six cell lines expressed endogenous IL-4, and IL-4 was
      detectable in the supernatant. Incubating cells with neutralising IL-4 antibodies
      resulted in a significant inhibition of basal growth in three cell lines,
      including IL-4-unresponsive MIA PaCa-2 cells, which however expressed the highest
      endogenous IL-4 levels. Interleukin-4 enhanced activity of MAPK, Akt-1, and Stat3
      in IL-4-responsive, but not in IL-4-unresponsive MIA PaCa-2 cells; however, IL-4
      enhanced tyrosine phosphorylation of insulin receptor substrate-1 and -2 in all
      cell lines. Our results demonstrate for the first time that pancreatic cancer
      cells produce IL-4 and that IL-4 can act as a growth factor in pancreatic cancer
      cells. Together with the observation that neutralising IL-4 antibodies can
      inhibit the growth of these cells, our results suggest that IL-4 may act as an
      autocrine growth factor in pancreatic cancer cells and also give rise to the
      possibility that cancer-derived IL-4 may suppress cancer-directed
      immunosurveillance in vivo in addition to its growth-promoting effects, thereby
      facilitating pancreatic tumour growth and metastasis.

PMID- 15714204
TI  - Genomic approaches in the management and treatment of breast cancer.
AB  - Breast cancer is the most common malignancy afflicting women from Western
      cultures. It has been estimated that approximately 211 000 women will be
      diagnosed with breast cancer in 2003 in the United States alone, and each year
      over 40 000 women will die of this disease. Developments in breast cancer
      molecular and cellular biology research have brought us closer to understanding
      the genetic basis of this disease. Unfortunately, this information has not yet
      been incorporated into the routine diagnosis and treatment of breast cancer in
      the clinic. Recent advancements in microarray technology hold the promise of
      further increasing our understanding of the complexity and heterogeneity of this
      disease, and providing new avenues for the prognostication and prediction of
      breast cancer outcomes. The most recent application of microarray genomic
      technologies to studying breast cancer will be the focus of this review.

PMID- 15714205
TI  - Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of
      patients with head and neck cancer.
AB  - Patients with squamous cell carcinoma of the head and neck (SCCHN) have depressed
      antitumour immunity. The presence of CD4+CD25+ (Treg) cells in these patients
      might be, in part, responsible for downregulation of antitumour immune responses.
      To evaluate the frequency and characteristics of Treg in the peripheral
      circulation of patients with SCCHN, we used multicolour flow cytometry.
      Expression of CCR7, CD62L, zeta chain and Annexin V binding to Treg and non-Treg
      CD4+ lymphocyte populations were evaluated. Treg were confirmed to be Foxp3+ and
      GITR+. The Treg frequency was significantly elevated in patients with active
      disease and those with no evidence of disease (NED) following curative therapies.
      Both Treg and non-Treg CD4+ T cells in patients were significantly enriched in
      CCR7- and CD62L- cell subsets. Although Treg in patients contained a higher
      proportion of double negative (CCR7-CD62L-) cells, the majority of Tregs were
      CCR7-CD62L+. The proportion of Annexin V+CD4+ T cells was higher in patients
      (P<0.00005) than normal controls (NC), and Treg were significantly more sensitive
      to apoptosis than non-Treg in patients and NC. Expression of zeta was reduced in
      all subsets of CD4+ T cells obtained from patients vs NC. The data suggest that
      Treg in patients with SCCHN largely contain T cells with the 'effector'
      phenotype, which bind Annexin V and have low zeta expression, consistent with
      their activation state and a rapid turnover in the peripheral circulation.

PMID- 15714206
TI  - The role of glucocorticoids in the induction of zinc-alpha2-glycoprotein
      expression in adipose tissue in cancer cachexia.
AB  - Loss of adipose tissue in cancer cachexia in mice bearing the MAC16 tumour arises
      from an increased lipid mobilisation through increased expression of zinc-alpha2
      glycoprotein (ZAG) in white (WAT) and brown (BAT) adipose tissue. Glucocorticoids
      have been suggested to increase ZAG expression, and this study examines their
      role in cachexia and the mechanisms involved. In mice bearing the MAC16 tumour,
      serum cortisol concentrations increased in parallel with weight loss, and the
      glucocorticoid receptor antagonist RU38486 (25 mg kg(-1)) attenuated both the
      loss of body weight and ZAG expression in WAT. Dexamethasone (66 microg kg(-1))
      administration to normal mice produced a six-fold increase in ZAG expression in
      both WAT and BAT, which was also attenuated by RU38486. In vitro studies using
      3T3-L1 adipocytes showed dexamethasone (1.68 microM) to stimulate lipolysis and
      increase ZAG expression, and both were attenuated by RU38486 (10 microM), anti
      ZAG antibody (1 microg ml(-1)), and the beta3-adrenoreceptor (beta3-AR)
      antagonist SR59230A (10 microM). Zinc-alpha2-glycoprotein also increased its own
      expression and this was attenuated by SR59230A, suggesting that it was mediated
      through the beta3-AR. This suggests that glucocorticoids stimulate lipolysis
      through an increase in ZAG expression, and that they are responsible for the
      increase in ZAG expression seen in adipose tissue of cachectic mice.

PMID- 15714207
TI  - NF-kappaB mediates proteolysis-inducing factor induced protein degradation and
      expression of the ubiquitin-proteasome system in skeletal muscle.
AB  - Loss of skeletal muscle in cancer cachexia has a negative effect on both
      morbidity and mortality. The role of nuclear factor-kappaB (NF-kappaB) in
      regulating muscle protein degradation and expression of the ubiquitin-proteasome
      proteolytic pathway in response to a tumour cachectic factor, proteolysis
      inducing factor (PIF), has been studied by creating stable, transdominant
      negative, muscle cell lines. Murine C(2)C(12) myoblasts were transfected with
      plasmids with a CMV promoter that had mutations at the serine phosphorylation
      sites required for degradation of I-kappaBalpha, an NF-kappaB inhibitory protein,
      and allowed to differentiate into myotubes. Proteolysis-inducing factor induced
      degradation of I-kappaBalpha, nuclear accumulation of NF-kappaB and an increase
      in luciferase reporter gene activity in myotubes containing wild-type, but not
      mutant, I-kappaBalpha proteins. Proteolysis-inducing factor also induced total
      protein degradation and loss of the myofibrillar protein myosin in myotubes
      containing wild-type, but not mutant, plasmids at the same concentrations as
      those causing activation of NF-kappaB. Proteolysis-inducing factor also induced
      increased expression of the ubiquitin-proteasome pathway, as determined by
      'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the
      beta-subunits of the proteasome, protein expression of 20S alpha-subunits and the
      19S subunits MSS1 and p42, as well as the ubiquitin conjugating enzyme, E2(14k),
      in cells containing wild-type, but not mutant, I-kappaBalpha. The ability of
      mutant I-kappaBalpha to inhibit PIF-induced protein degradation, as well as
      expression of the ubiquitin-proteasome pathway, confirms that both of these
      responses depend on initiation of transcription by NF-kappaB.

PMID- 15714208
TI  - Mutation screening and association study of RNASEL as a prostate cancer
      susceptibility gene.
AB  - To date, germline mutations have been found in three candidate genes for
      hereditary prostate cancer: ELAC2 at 17p11, RNASEL at 1q25 and MSR1 at 8p22.
      RNASEL, encoding the 2',5'-oligoadenylate-dependant RNase L, seems to have rare
      mutations in different ethnicities, such as M1I in Afro-Americans, E265X in men
      of European descent and 471delAAAG in Ashkenazi Jews. In order to evaluate the
      relevance of RNASEL in the German population, we sequenced its open reading frame
      to determine the spectrum and frequency of germline mutations. The screen
      included 303 affected men from 136 Caucasian families, of which 45 met the
      criteria for hereditary prostate cancer. Variants were analysed using a family
      based association test, and genotyped in an additional 227 sporadic prostate
      cancer patients and 207 controls. We identified only two sib pairs (1.4% of our
      families) cosegregating conspicuous RNASEL variants with prostate cancer: the
      nonsense mutation E265X, and a new amino-acid substitution (R400P) of unknown
      functional relevance. Both alleles were also found at low frequencies (1.4 and
      0.5%, respectively) in controls. No significant association of polymorphisms
      (I97L, R462Q and D541E) was observed, neither in case-control analyses nor by
      family-based association tests. In contrast to previous reports, our study does
      not suggest that common variants (i.e. R462Q) modify disease risk. Our results
      are not consistent with a high penetrance of deleterious RNASEL mutations. Due to
      the low frequency of germline mutations present in our sample, RNASEL does not
      have a significant impact on prostate cancer susceptibility in the German
      population.

PMID- 15714209
TI  - Increasing the intracellular availability of all-trans retinoic acid in
      neuroblastoma cells.
AB  - Recent data indicate that isomerisation to all-trans retinoic acid (ATRA) is the
      key mechanism underlying the favourable clinical properties of 13-cis retinoic
      acid (13cisRA) in the treatment of neuroblastoma. Retinoic acid (RA) metabolism
      is thought to contribute to resistance, and strategies to modulate this may
      increase the clinical efficacy of 13cisRA. The aim of this study was to test the
      hypothesis that retinoids, such as acitretin, which bind preferentially to
      cellular retinoic acid binding proteins (CRABPs), or specific inhibitors of the
      RA hydroxylase CYP26, such as R116010, can increase the intracellular
      availability of ATRA. Incubation of SH-SY5Y cells with acitretin (50 microM) or
      R116010 (1 or 10 microM) in combination with either 10 microM ATRA or 13cisRA
      induced a selective increase in intracellular levels of ATRA, while 13cisRA
      levels were unaffected. CRABP was induced in SH-SY5Y cells in response to RA. In
      contrast, acitretin had no significant effect on intracellular retinoid
      concentrations in those neuroblastoma cell lines that showed little or no
      induction of CRABP after RA treatment. Both ATRA and 13cisRA dramatically induced
      the expression of CYP26A1 in SH-SY5Y cells, and treatment with R116010, but not
      acitretin, potentiated the RA-induced expression of a reporter gene and CYP26A1.
      The response of neuroblastoma cells to R116010 was consistent with inhibition of
      CYP26, indicating that inhibition of RA metabolism may further optimise retinoid
      treatment in neuroblastoma.

PMID- 15714210
TI  - Comparison of 1- and 2-year screening intervals for women undergoing screening
      mammography.
AB  - We compared the long-term impact of 1- and 2-year screening mammography intervals
      using prognostic, screening, and outcome information for women aged 50-74 years
      obtained from the Screening Mammography Program of British Columbia in two time
      periods, prior to 1997 (policy of annual mammography) and after 1997 (biennial
      mammography). Survival was estimated for both periods using a prognostic model
      and the expected rate of interval and screen-detected cancers. The likelihood of
      a screen-detected cancer with annual screening was 2.32 per thousand screens and
      with biennial screening was 3.32 per thousand screens. The prognostic profile of
      screen-detected cancers was better than that of interval cancers. Among both
      screen-detected and interval cancers, the prognostic profiles with annual and
      biennial screening were similar. The estimated breast cancer-specific survival
      rates for women undergoing annual and biennial screening mammography were 95.2
      and 94.6% at 5 years, and 90.4 and 89.2% at 10 years, respectively. Annual
      compared to biennial mammography was associated with a 1.2% increase in the
      estimated 10-year breast cancer-specific survival for women aged 50-74 years,
      diagnosed with invasive breast cancer after screening programme attendance.

PMID- 15714212
TI  - Reliability and validity of the combined heart rate and movement sensor
      Actiheart.
AB  - Accurate quantification of physical activity energy expenditure is a key part of
      the effort to understand disorders of energy metabolism. The Actiheart, a
      combined heart rate (HR) and movement sensor, is designed to assess physical
      activity in populations. OBJECTIVE: To examine aspects of Actiheart reliability
      and validity in mechanical settings and during walking and running. METHODS: In
      eight Actiheart units, technical reliability (coefficients of variation, CV) and
      validity for movement were assessed with sinusoid accelerations (0.1-20 m/s(2))
      and for HR by simulated R-wave impulses (25-250 bpm). Agreement between Actiheart
      and ECG was determined during rest and treadmill locomotion (3.2-12.1 km/h).
      Walking and running intensity (in J/min/kg) was assessed with indirect
      calorimetry in 11 men and nine women (26-50 y, 20-29 kg/m(2)) and modelled from
      movement, HR, and movement + HR by multiple linear regression, adjusting for sex.
      RESULTS: Median intrainstrument CV was 0.5 and 0.03% for movement and HR,
      respectively. Corresponding interinstrument CV values were 5.7 and 0.03% with
      some evidence of heteroscedasticity for movement. The linear relationship between
      movement and acceleration was strong (R(2) = 0.99, P < 0.001). Simulated R-waves
      were detected within 1 bpm from 30 to 250 bpm. The 95% limits of agreement
      between Actiheart and ECG were -4.2 to 4.3 bpm. Correlations with intensity were
      generally high (R(2) > 0.84, P < 0.001) but significantly highest when combining
      HR and movement (SEE < 1 MET). CONCLUSIONS: The Actiheart is technically reliable
      and valid. Walking and running intensity may be estimated accurately but further
      studies are needed to assess validity in other activities and during free-living.
      SPONSORSHIP: The study received financial support from the Wellcome Trust and SB
      was supported by a scholarship from Unilever, UK.

PMID- 15714213
TI  - Nutritional status of patients hospitalised in Poland.
AB  - AIM: Screening and extended assessment of the nutritional status of patients on
      admission and on discharge from hospital were carried out. DESCRIPTION: The
      studies were carried out in four teaching hospitals, four provincial hospitals
      and four county hospitals in Poland. SUBJECTS: Screening examinations were
      carried out for 3310 randomly selected patients (every 10th patient admitted to
      hospital, including 1916 female cases aged from 16 to 92 y and 1394 male patients
      aged from 16 to 100 y). Extended examinations were carried out on 210 patients
      aged from 16 to 87 y (including 122 female and 88 male). MAIN ASSESSMENT
      PARAMETERS: Anthropometric (height, weight, body mass index (BMI), waist-to-hip
      ratio (WHR), arm circumference) and biochemical indices (erythrocyte count,
      haemoglobin concentration, white blood cell count, blood lymphocyte count and
      serum albumin serum concentration). The extended examinations included
      determination of antioxidant vitamins (A, C, E), vitamin B(12) and folic acid.
      RESULTS: On admission to hospital, 10.43% of the patients surveyed had a BMI
      below 20 kg/m(2), in 20.74% of patients serum albumin concentration was below 3.5
      g/dl, indicating possible protein energy malnutrition. In addition, 21.02% had
      lymphocyte count below 1.5 x 10(3)/mm(3). During hospitalisation, deterioration
      in the nutritional status of the patient population occurred. On discharge from
      hospital, the percentage of patients with BMI < 20 kg/m(2) increased to 11.21%
      and the percentage with low blood albumin (<3.5 g/dl) increased to 28.57%. On
      admission, vitamin C deficiency was present in 51.8% of patients, folic acid
      deficiency in 32%, vitamin E deficiency in 10%, vitamin B(12) deficiency in 6.8%
      and vitamin A deficiency in 1.4%. Vitamin deficiencies were present equally in
      malnourished, overweight and obese patients. CONCLUSIONS: In patients admitted to
      hospitals in Poland, malnutrition risk demonstrated by BMI was observed in 10.43%
      of patients. On the basis of biochemical indices, increased nutritional risk was
      demonstrated in 21% of patients. Vitamin malnutrition was seen in the majority of
      patients. A significant correlation between weight, BMI, arm circumference, blood
      lymphocyte count and the number of days spent in hospital was observed.
      SPONSORSHIP: The Committee of Scientific Research and the Ministry of Health-PBZ
      012-14.

PMID- 15714214
TI  - It's good to talk: children's views on food and nutrition.
AB  - OBJECTIVE: To gain an insight into children's views about food and nutrition.
      DESIGN: Data were collected in focus group discussions; two focus group sessions
      were undertaken with each school group. SETTING: A total of 11 postprimary
      schools in Northern Ireland and England. SUBJECTS: In all, 106 children aged 11
      12-y-old (n = 52 boys, n = 54 girls). RESULTS: Focus group transcripts were
      analysed using qualitative research methodology. Major barriers to healthy eating
      were taste, appearance of food, filling power, time/effort, cost,
      choice/availability, risk, rebellion, and body image/weight concerns. The main
      difference between sexes was in terms of motivating factors for eating well;
      girls tended to focus primarily on their appearance whereas boys appeared to be
      more influenced by sport. There was some mention of balance and variety within
      the focus group discussions, however, in practice, the children had a tendency to
      categorise foods as either 'good' or 'bad', 'healthy' or 'unhealthy'.
      CONCLUSIONS: This study has revealed a number of barriers to, and motivations
      for, healthy eating, which should be taken into account when planning nutrition
      intervention strategies aimed at children moving into adolescence. While it may
      be possible to immediately attempt to address some of the barriers identified in
      this study, for example, in nutrition education initiatives, other barriers (such
      as the lack of available, attractive and affordable healthy foods in the school
      canteen) will prove more difficult to tackle without changes at the policy level.
      Overall, it appears that health promotion specialists have a major challenge
      ahead in order to encourage this age group to view healthy eating as an
      attractive and achievable behaviour. SPONSORSHIP: Food Standards Agency, London,
      UK.

PMID- 15714215
TI  - Teenage girls and elderly women living in northern Europe have low winter vitamin
      D status.
AB  - OBJECTIVE: To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD)
      in adolescent girls and elderly community-dwelling women living in four countries
      of northern Europe and to explain differences in S-25OHD concentrations between
      and within the countries. DESIGN: A cross-sectional observational study conducted
      in a standardised way during February-March. S-25OHD was analysed by high
      performance liquid chromatography. Vitamin D and calcium intake was calculated
      using a standardised food composition database. SETTING: Denmark, Finland,
      Ireland, and Poland. SUBJECTS: A total of 199 girls (mean (s.d.) age 12.6 (0.5)
      y) and 221 women (mean (s.d.) age 71.8 (1.4) y). RESULTS: The median (inter
      quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls
      and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in
      37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in
      92% of the girls and 37% of the women. Positive significant determinants for S
      25OHD in girls were use of vitamin D supplements, and in women sun habits,
      dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass
      index and smoking were negative determinants in women. For women predictors could
      explain the differences between countries (P(country) = 0.09, R(2) = 0.39), but
      for girls the difference remained significant even after including predictors
      (P(country) = 0.03, R(2) = 0.15). CONCLUSION: Vitamin D status is low in northern
      Europe during winter. More than one-third of the adolescent girls have vitamin D
      status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the
      elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of
      vitamin D supplements is a significant positive determinant for S-25OHD for both
      girls and women (P = 0.001). SPONSORSHIP: The European Fifth Framework Programme
      (Contract No. QLK1-CT-2000-00623).

PMID- 15714216
TI  - Reliability of calculating body mass index centile.
AB  - OBJECTIVE: Body mass index (BMI) centile is recommended for assessing body
      fatness in children. We compared the reliability of two methods of deriving BMI
      centile. METHOD: A total of 42 dietitians calculated the BMI centiles of six
      children, half using the Cole Calculator (a slide rule) and half calculating by
      hand and plotting on the BMI centile chart. RESULTS: The centile chart method was
      more reliable than the Cole Calculator, probably due to its greater familiarity.

PMID- 15714217
TI  - Netherlands research programme weight gain prevention (NHF-NRG): rationale,
      objectives and strategies.
AB  - OBJECTIVE: To outline the rationale, objectives and strategies used in a
      systematically designed research programmme to study specific weight gain
      inducing behaviours, their social-psychological as well as environmental
      determinants, and the effects of interventions aimed at the prevention of weight
      gain. DESIGN: The evidence for potential behavioural determinants and strategies
      to prevent weight gain was reviewed, and the methods applied within the
      Netherlands Research programme weight gain prevention (NHF-NRG) project were
      described. The project is designed according to the Intervention Mapping
      protocol. SETTING: The Netherlands. SUBJECTS: The main target groups are (a)
      adolescents (12-16 y) in secondary school, (b) young adults (20-40 y) at the
      workplace and (c) recently retired people (55-65 y) at home. INTERVENTIONS: Each
      intervention includes an individual component, in which computer-tailored
      information is provided. Additionally, interventions are aimed at changing
      environmental components. RESULTS: The short-term results of this project can be
      expected by the beginning of 2005. Guidelines for nationwide weight gain
      prevention, based on this research programme, will become available in 2007.
      CONCLUSIONS: Based on the few interventions that were evaluated to date, no
      robust conclusions can be drawn regarding the effectiveness of obesity
      prevention. The systematic and multidisciplinary design of the NHF-NRG programme
      enables the identification of potentially effective methods and strategies for
      the prevention of weight gain.

PMID- 15714218
TI  - Contribution of 'noncore' foods and beverages to the energy intake and weight
      status of Australian children.
AB  - OBJECTIVES: The Australian Guide to Healthy Eating is based on five core food
      groups and water. Foods or beverages that do not fit into these groups are
      considered extra or 'noncore'. We tested the hypotheses that noncore foods and
      beverages make a greater proportional contribution to mean daily energy intakes
      of: (1) children, compared with other age groups; and (2) overweight and obese
      children, compared with healthy weight children. DESIGN, SETTING AND SUBJECTS: We
      used data from 13 858 participants aged 2 to 80+ y who had 24-h dietary recall
      data collected in the 1995 cross-sectional Australian National Nutrition Survey.
      ANOVA was used to compare the percentage of energy provided by noncore foods and
      beverages by age and weight status. RESULTS: Children (5 to 12 y) and adolescents
      (13 to 18 y) obtained significantly more (P < 0.001) of their daily food energy
      from noncore foods (41.5 and 43.4%, respectively) than all other age groups.
      These age groups also obtained significantly more (P < 0.001) of their daily
      beverage energy from noncore beverages (30.7 and 36.9%, respectively). Results
      were not consistent with weight status, although very young (2-4 y) obese
      children obtained significantly more energy (P < 0.05) from noncore beverages
      than children in a healthy weight range. Younger children may also have consumed
      a greater quantity of foods and beverages. Under-reporting may have obscured
      similar results for older children. CONCLUSIONS: By definition, noncore foods and
      beverages are surplus to the requirements of a healthy diet. We found that
      Australian children consume these foods and beverages in excess.

PMID- 15714219
TI  - Gene therapy: the 'pro-sense' approach to Duchenne muscular dystrophy.

PMID- 15714220
TI  - Closing the gap between rocks and clocks.

PMID- 15714221
TI  - Gene flow among established Puerto Rican populations of the exotic tree species,
      Albizia lebbeck.
AB  - We estimate gene flow and patterns of genetic diversity in Albizia lebbeck, an
      invasive leguminous tree in the dry forest of southwestern Puerto Rico. Genetic
      diversity estimates calculated for 10 populations of 24 trees each indicated that
      these populations may have been formed from multiple introductions. The presence
      of unique genotypes in the northernmost populations suggests that novel genotypes
      are still immigrating into the area. This combination of individuals from
      disparate locations led to high estimates of genetic diversity (He = 0.266, P =
      0.67). Indirect estimates of gene flow indicate that only 0.69 migrants per
      generation move between populations, suggesting that genetic diversity within
      populations should decrease due to genetic drift. Since migration-drift
      equilibrium was not found, however, this estimate needs to be viewed with
      caution. The regular production of pods in this outcrossing species (tm = 0.979)
      indicates that sufficient outcross pollen is received to insure successful
      reproduction. Direct estimates of gene flow indicate that between 44 and 100% of
      pollen received by trees in four small stands of trees (n < 11) was foreign. The
      role of gene flow in facilitating the spread of this invasive plant species is
      discussed.

PMID- 15714222
TI  - A source-to-dose assessment of population exposures to fine PM and ozone in
      Philadelphia, PA, during a summer 1999 episode.
AB  - A novel source-to-dose modeling study of population exposures to fine particulate
      matter (PM(2.5)) and ozone (O(3)) was conducted for urban Philadelphia. The study
      focused on a 2-week episode, 11-24 July 1999, and employed the new integrated and
      mechanistically consistent source-to-dose modeling framework of MENTOR/SHEDS
      (Modeling Environment for Total Risk studies/Stochastic Human Exposure and Dose
      Simulation). The MENTOR/SHEDS application presented here consists of four
      components involved in estimating population exposure/dose: (1) calculation of
      ambient outdoor concentrations using emission-based photochemical modeling, (2)
      spatiotemporal interpolation for developing census-tract level outdoor
      concentration fields, (3) calculation of microenvironmental concentrations that
      match activity patterns of the individuals in the population of each census tract
      in the study area, and (4) population-based dosimetry modeling. It was found that
      the 50th percentiles of calculated microenvironmental concentrations of PM(2.5)
      and O(3) were significantly correlated with census-tract level outdoor
      concentrations, respectively. However, while the 95th percentiles of O(3)
      microenvironmental concentrations were strongly correlated with outdoor
      concentrations, this was not the case for PM(2.5). By further examining the
      modeled estimates of the 24-h aggregated PM(2.5) and O(3) doses, it was found
      that indoor PM(2.5) sources dominated the contributions to the total PM(2.5)
      doses for the upper 5 percentiles, Environmental Tobacco Smoking (ETS) being the
      most significant source while O(3) doses due to time spent outdoors dominated the
      contributions to the total O(3) doses for the upper 5 percentiles. The
      MENTOR/SHEDS system presented in this study is capable of estimating intake dose
      based on activity level and inhalation rate, thus completing the source-to-dose
      modeling sequence. The MENTOR/SHEDS system also utilizes a consistent basis of
      source characterization, exposure factors, and human activity patterns in
      conducting population exposure assessment of multiple co-occurring air
      pollutants, and this constitutes a primary distinction from previous studies of
      population exposure assessment, where different exposure factors and activity
      patterns would be used for different pollutants. Future work will focus on
      incorporating the effects of commuting patterns on population exposure/dose
      assessments as well as on extending the MENTOR/SHEDS applications to
      seasonal/annual studies and to other areas in the U.S.

PMID- 15714223
TI  - Alpha-2 adrenoceptor activation inhibits phencyclidine-induced deficits of
      spatial working memory in rats.
AB  - N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, such as phencyclidine
      (PCP), induce behavioral abnormalities (locomotor hyperactivity, sensorimotor
      gating deficits, impairments of cognition) in animals that are thought to model
      aspects of schizophrenia. The administration of PCP increases noradrenaline
      transmission in the rat prefrontal cortex, a brain structure required for normal
      cognitive processes. Noradrenaline, in turn, works through a set of receptors
      that have themselves been implicated directly in NMDA antagonist-induced
      deficits; we recently reported that the alpha-2 agonist, clonidine, is effective
      at preventing PCP-induced deficits of working memory and visual attention in
      rats. Here, we further investigated the role for alpha-2 adrenoreceptors in the
      effects of PCP on spatial working memory performance. The alpha-2 agonist
      clonidine (0.001-0.01 mg/kg, subcutaneously (s.c.)) produced a significant
      amelioration of PCP-induced working memory deficits; the effects of PCP (1.0
      mg/kg, s.c.), but not clonidine, were reduced in noradrenaline-depleted rats. In
      addition, the alpha-2A-preferring agonist guanfacine (0.05-1.0 mg/kg, s.c.) dose
      dependently prevented the deficits of spatial working memory performance produced
      by PCP. Although the highly selective alpha-2 receptor antagonist, atipamezole
      (ATI), failed to affect spatial working memory on its own, at the doses studied
      (0.1-0.5 mg/kg, s.c.), it dramatically enhanced the working memory deficit
      produced by PCP. These data indicate that alpha-2 adrenoreceptors tonically
      inhibit PCP-induced deficits of spatial working memory, suggesting an important
      role for these receptors in cognitive deficits associated with NMDA receptor
      hypofunction.

PMID- 15714224
TI  - Melatonin treatment of winter depression following total sleep deprivation:
      waking EEG and mood correlates.
AB  - Patients with winter depression (seasonal affective disorder (SAD)) commonly
      complain of sleepiness. Sleepiness can be objectively measured by spectral
      analysis of the waking electroencephalogram (EEG) in the 1-10 Hz band. The waking
      EEG was measured every 3 h in 16 female SAD patients and 13 age-matched control
      women throughout a total sleep deprivation of 30 h. Melatonin (or placebo) under
      double-blind conditions was administered subsequently (0.5 mg at 1700 h for 6
      days), appropriately timed to phase advance circadian rhythms, followed by
      reassessment in the laboratory for 12 h. The increase in EEG power density in a
      narrow theta band (5-5.99 Hz, derivation Fz-Cz) during the 30 h protocol was
      significantly attenuated in patients compared with controls (difference between
      linear trends p=0.037). Sleepiness (p=0.092) and energy (p=0.045) self-ratings
      followed a similar pattern. Six patients improved after sleep deprivation (> or
      =50% reduction on SIGH-SAD(22) score). EEG power density dynamics was correlated
      with clinical response to sleep deprivation: the steeper the build-up (as in
      controls), the better the improvement (p<0.05). There was no differential effect
      of melatonin or placebo on any measure; both treatments stabilized the
      improvement. Overall, patients with winter depression manifest similar wake EEG
      characteristics as long sleepers or late chronotype with respect to an
      insufficient build-up of homeostatic sleep pressure. Sleep deprivation was an
      effective antidepressant treatment for some patients, but evening melatonin was
      not more efficacious than placebo in sustaining this antidepressant effect.

PMID- 15714225
TI  - Stress-induced c-Fos expression is differentially modulated by dexamethasone,
      diazepam and imipramine.
AB  - Immobilization stress upregulates c-Fos expression in several CNS areas. Repeated
      stress or the use of drugs can modulate stress-induced c-Fos expression. Here, we
      investigated in 40 different areas of the rat brain the effects of dexamethasone
      (SDX, a synthetic glucocorticoid), diazepam (SBDZ, a benzodiazepine), and
      imipramine (IMI, an antidepressant) on the c-Fos expression induced by restraint
      stress. Wistar rats were divided into four groups and submitted to 20 days of
      daily injection of saline (three first groups) or imipramine, 15 mg/kg, i.p. On
      day 21, animals were submitted to injections of saline (somatosensory, SS), SDX
      (1 mg/kg, i.p.), SBDZ (5 mg/kg, i.p.), or IMI (15 mg/kg, i.p.) before being
      submitted to restraint. Immediately after stress, the animals were perfused and
      their brains processed with immunohistochemistry for c-Fos (Ab-5 Oncogene
      Science). Dexamethasone reduced stress-induced c-Fos expression in SS cortex,
      hippocampus, paraventricular nucleus of the hypothalamus (PVH), and locus
      coeruleus (LC), whereas diazepam reduced c-Fos staining in the SS cortex,
      hippocampus, bed nucleus of stria terminalis, septal area, and hypothalamus
      (preoptic area and supramammillary nucleus). Chronic administration of imipramine
      decreased staining in the hippocampus, PVH, and LC, while increasing it in the
      nucleus raphe pallidus. We conclude that dexamethasone, diazepam and imipramine
      differentially modulate stress-induced Fos expression. The present study provides
      an important comparative background that may help in the further understanding of
      the effects of these compounds and on the brain activation as well as on the
      behavioral, neuroendocrine, and autonomic responses to stress.

PMID- 15714226
TI  - Mild interoceptive stressors affect learning and reactivity to contextual cues:
      toward understanding the development of unexplained illnesses.
AB  - Contextual learning is evident with repeated experiences with agents and
      treatments that induce frank illness and interoceptive stress. Here, we examined
      whether acute treatment with mild interoceptive stressors (low doses of
      pyridostigmine bromide (PB), neostigmine bromide (NB), and interleukin (IL)
      1beta) may serve as unconditional stimuli supporting contextual learning. Rats
      were exposed to interoceptive and exteroceptive stressors in contexts
      distinguished by visual or olfactory cues. Acoustic startle responses (ASRs) were
      measured the day following exposure and 2 weeks thereafter, without delivery of
      the unconditional stimuli. The appearance, form, and duration of startle
      potentiation depended on the distinguishing features of the context and the
      nature of the interoceptive stressor. Rats given cholinesterase inhibitors (PB
      and NB), but not IL-1beta or exposed to an exteroceptive stressor, exhibited
      exaggerated ASRs in a novel context distinguished by visual cues. Treatment with
      either PB or IL-1beta led to potentiated ASRs in the presence of odors congruent
      with those experiences during exposure to the stressor. Startle potentiation by
      odor was still apparent 2 weeks after treatment. For contexts differentiated by
      visual stimuli, cholinomimetics transiently alter reactivity within novel
      contexts. In the case of contexts differentiated by odors, learning is apparent
      at least 2 weeks after acute treatment of cholinomimetics and IL-1beta.
      Contextual learning and changes in reactivity consequent to mild interoceptive
      stressors such as PB may play a role in the development of nonspecific symptoms
      typical of unexplained illnesses, such as Gulf War Illness.

PMID- 15714227
TI  - Neurological and cognitive recovery following abstinence from petrol sniffing.
AB  - Anecdotal observations suggest that neurological impairments associated with
      petrol (gasoline) sniffing resolve with abstinence, although these effects have
      not been proven empirically. Severe exposure to leaded petrol may induce a lead
      encephalopathy that extends beyond any acute intoxication and requires emergency
      hospital treatment. Previously, in chronic petrol sniffers, we showed
      neurological, saccadic, and cognitive abnormalities that were more severe in
      petrol sniffers with a history of hospitalization for lead encephalopathy, and
      that correlated with blood lead levels and the length of time of sniffing petrol.
      Ex-petrol sniffers showed a qualitatively similar but quantitatively less severe
      pattern of impairment. Petrol sniffing was stopped completely in one of the study
      communities by modifying social, occupational, and recreational opportunities.
      After 2 years, we obtained biochemical and neurobehavioral (neurological,
      saccade, and cognitive) data from all available participants of the earlier study
      including 10 nonsniffers and 29 chronic petrol sniffers, with six of these
      individuals previously receiving hospital treatment for lead encephalopathy.
      Here, we report that blood lead was reduced and that neurobehavioral impairments
      improved, and in many cases normalized completely. The most severe petrol-related
      neurobehavioral impairment was observed among individuals who had longer
      histories of abuse and higher blood lead levels, and among petrol sniffers with a
      history of lead encephalopathy. Those with the greatest extent of neurobehavioral
      impairment showed the greatest degree of improvement with abstinence, but were
      less likely to recover completely. This is the first direct evidence that
      neurological and cognitive impairment from chronic petrol sniffing ameliorates
      with abstinence and may recover completely.

PMID- 15714228
TI  - Hypothalamic-pituitary-adrenal axis activity and sleep in posttraumatic stress
      disorder.
AB  - Alterations of the hypothalamic-pituitary-adrenal (HPA) axis and sleep
      disturbances have been described separately in post-traumatic stress disorder
      (PTSD). It is not known if HPA alterations and sleep disturbances are associated
      in PTSD. This study examined sleep and HPA activity in 20 male medication-free
      subjects with PTSD and 16 matched healthy controls. Two nights of polysomnography
      were obtained and 24-h urinary cortisol was collected during day 2. Subjects self
      administered a low-dose (0.5 mg) salivary dexamethasone test at home. Compared
      with controls, PTSD subjects had higher 24-h urinary microg cortisol/g creatinine
      (mean+/-SD 40+/-17 vs 28+/-12, p=0.03) but not significantly higher 24-h urinary
      cortisol (mean+/-SD 52+/-15 microg/day vs 43+/-23, p=0.19). PTSD subjects showed
      a trend towards less cortisol suppression after dexamethasone (73%+/-18 vs 83%+/
      10, p=0.06). In the combined sample, delta sleep was significantly and negatively
      correlated with 24-h urinary cortisol (r=-0.36, p=0.04), and with 24-h urinary
      cortisol/g creatinine on a trend level (r=-0.34, p=0.06). Our results suggest
      that increased cortisol is negatively associated with delta sleep. This may
      contribute to sleep abnormalities in conditions associated with elevated
      cortisol, possibly including PTSD. Future studies should explore the temporal
      relationship between HPA activity, sleep disturbances, and psychopathology after
      a traumatic event.

PMID- 15714229
TI  - Low genetic diversity among Frankia spp. strains nodulating sympatric populations
      of actinorhizal species of Rosaceae, Ceanothus (Rhamnaceae) and Datisca glomerata
      (Datiscaceae) west of the Sierra Nevada (California).
AB  - Frankia spp. strains typically induce N2-fixing root nodules on actinorhizal
      plants. The majority of host plant taxa associated with the uncultured Group 1
      Frankia strains, i.e., Ceanothus of the Rhamnaceae, Datisca glomerata
      (Datiscaceae), and all actinorhizal members of the Rosaceae except Dryas, are
      found in California. A study was conducted to determine the distribution of
      Frankia strains among root nodules collected from both sympatric and solitary
      stands of hosts. Three DNA regions were examined, the 5' end of the 16S rRNA
      gene, the internal transcribed spacer region between the 16S and 23S rRNA genes,
      and a portion of the glutamine synthetase gene (glnA). The results suggest that a
      narrow range of Group 1 Frankia spp. strains dominate in root nodules collected
      over a large area of California west of the Sierra Nevada crest with no apparent
      host-specificity. Comparisons with Group 2 Frankia strain diversity from Alnus
      and Myrica within the study range suggest that the observed low diversity is
      peculiar to Group 1 Frankia strains only. Factors that may account for the
      observed lack of genetic variability and host specificity include strain
      dominance over a large geographical area, current environmental selection, and
      (or) a past evolutionary bottleneck.

PMID- 15714230
TI  - Cryptococcus festucosus sp. nov. a new hymenomycetous yeast in the Holtermannia
      clade.
AB  - Five yeast strains belonging to the genus Cryptococcus Vuillemin were isolated
      from steppe plants and turf collected in the Prioksko-terrasny biosphere reserve
      (Moscow region, Russia). Sequence analyses of the D1/D2 domains of the 26S rDNA
      and of the internal transcribed spacer region revealed that these yeast strains
      and strain CBS 8016 have almost identical sequences and belong to the
      Holtermannia clade of the Tremellomycetidae (Basidiomycota, Hymenomycetes). A
      novel species named Cryptococcus festucosus (type strain VKM Y-2930) is proposed
      to accommodate these strains. Physiological characteristics and mycocin
      sensitivity patterns distinguishing Cryptococcus festucosus from the other
      species of this clade are presented.

PMID- 15714231
TI  - Fate of Escherichia coli O157:H7 in irrigation water on soils and plants as
      validated by culture method and real-time PCR.
AB  - One of the most common vehicles by which Escherichia coli O157:H7 may be
      introduced into crops is contaminated irrigation water. Water contamination is
      becoming more common in rural areas of the United States as a result of large
      animal operations, and up to 40% of tested drinking-water wells are contaminated
      with E. coli. In this study, 2 contrasting soil samples were inoculated with E.
      coli O157:H7 expressing green fluorescent protein through irrigation water. Real
      time PCR and culture methods were used to quantify the fate of this pathogen in
      phyllosphere (leaf surface), rhizosphere (volume of soil tightly held by plant
      roots), and non-rhizosphere soils. A real-time PCR assay was designed with the
      eae gene of E. coli O157:H7. The probe was incorporated into real-time PCR
      containing DNA extracted from the phyllosphere, rhizosphere, and non-rhizosphere
      soils. The detection limit for E. coli O157:H7 quantification by real-time PCR
      was 1.2 x 10(3) in the rhizosphere, phyllosphere, and non-rhizosphere samples. E.
      coli O157:H7 concentrations were higher in the rhizosphere than in the non
      rhizosphere soils and leaf surfaces, and persisted longer in clay soil. The
      persistence of E. coli O157:H7 in phyllosphere, rhizosphere, and non-rhizosphere
      soils over 45 days may play a significant part in the recontamination cycle of
      produce in the environment. Therefore, the rapidity of the real-time PCR assay
      may be a useful tool for quantification and monitoring of E. coli O157:H7 in
      irrigation water and on contaminated fresh produce.

PMID- 15714232
TI  - Endophytic fungal diversity of 2 sand dune wild legumes from the southwest coast
      of India.
AB  - Endophytic fungi of 3 age classes (seeds, seedlings, and mature plants) and 5
      tissue classes (cotyledons, seed coats, roots, stems, and leaves) of coastal sand
      dune legumes Canavalia cathartica and Canavalia maritima were assessed by plating
      surface-sterilized segments on malt extract agar. Forty-six fungal taxa
      comprising 6 ascomycetes, 33 mitosporic fungi, 2 zygomycetes, and 5 sterile
      morphospecies were recovered. There was no significant difference in the
      colonization frequency of endophytes between plant species (p = 0.4098, Student's
      t test). Among the age classes, endophytic fungi colonized over 90% of seedlings
      and mature plants. Similarly, among tissue classes, endophytic fungi colonized
      over 90% of root, stem, and leaf segments. Diversity and richness of endophytic
      fungi were higher in C. cathartica than in C. maritima. Rarefaction curves
      revealed a "higher expected number of species" in mature plants of C. cathartica
      and seedlings of C. maritima, whereas it was highest in leaves of both plant
      species. The most dominant endophyte, Chaetomium globosum, colonized over 50% of
      the root, stem, and leaf segments of C. maritima and over 50% of the root
      segments of C. cathartica. The colonization frequency of C. globosum was found to
      be 5%-12.5% in seeds and increased up to 40%-64.4% in seedlings or mature plants.
      Halosarpheia sp. was the only marine fungus recovered among the endophytes.

PMID- 15714233
TI  - Characteristics of rhizobia nodulating beans in the central region of Minnesota.
AB  - Until recently, beans (Phaseolus vulgaris L.) grown in Minnesota were rarely
      inoculated. Because of this, we hypothesized that bean rhizobia collected in
      Minnesota would either share characteristics identifiable with Rhizobium etli of
      Mesoamerican or Andean origin, introduced into the region as seed-borne
      contaminants, or be indigenous rhizobia from prairie species, such as Dalea spp.
      The latter organisms have been shown to nodulate and fix N2 with Phaseolus
      vulgaris. Rhizobia recovered from the Staples, Verndale, and Park Rapids areas of
      Minnesota were grouped according to the results of BOXA1R-PCR fingerprint
      analysis into 5 groups, with only one of these having banding patterns similar to
      2 of 4 R. etli reference strains. When representative isolates were subject to
      fatty acid - methyl ester analysis and 16S rRNA gene sequence analysis, the
      results obtained differed. 16S rRNA gene sequences of half the organisms tested
      were most similar to Rhizobium leguminosarum. Rhizobia from Dalea spp., an
      important legume in the prairie ecosystem, did not play a significant role as the
      microsymbiont of beans in this area. This appears to be due to the longer time
      needed for them to initiate infection in Phaseolus vulgaris. Strains of Rhizobium
      tropici IIB, including UMR1899, proved tolerant to streptomycin and captan, which
      are commonly applied as seed treatments for beans. Local rhizobia appeared to
      have very limited tolerance to these compounds.

PMID- 15714234
TI  - Optimization of extracellular fungal peroxidase production by 2 Coprinus species.
AB  - Optimum culture conditions for the batch production of extracellular peroxidase
      by Coprinus cinereus UAMH 4103 and Coprinus sp. UAMH 10067 were explored using 2
      statistical experimental designs, including 2-level, 7-factor fractional
      factorial design and 2-factor central composite design. Of the 7 factors examined
      in the screening study, the concentrations of carbon (glucose) and nitrogen
      (peptone or casitone) sources showed significant effects on the peroxidase
      production by Coprinus sp. UAMH 10067. The optimum glucose and peptone
      concentrations were determined as 2.7% and 0.8% for Coprinus sp. UAMH 10067, and
      2.9% and 1.4% for C. cinereus UAMH 4103, respectively. Under the optimized
      culture condition the maximum peroxidase activity achieved in this study was 34.5
      U x mL(-1) for Coprinus sp. UAMH 10067 and 68.0 U x mL(-1) for C. cinereus UAMH
      4103, more than 2-fold higher than the results of previous studies.

PMID- 15714235
TI  - In vitro attachment of phylloplane yeasts to Botrytis cinerea, Rhizoctonia
      solani, and Sclerotinia homoeocarpa.
AB  - The ability of yeasts to attach to hyphae or conidia of phytopathogenic fungi has
      been speculated to contribute to biocontrol activity on plant surfaces.
      Attachment of phylloplane yeasts to Botrytis cinerea, Rhizoctonia solani, and
      Sclerotinia homoeocarpa was determined using in vitro attachment assays. Yeasts
      were incubated for 2 d on potato dextrose agar (PDA) prior to experimentation. A
      total of 292 yeasts cultured on PDA were screened for their ability to attach to
      conidia of B. cinerea; 260 isolates (89.1%) attached to conidia forming large
      aggregates of cells, and 22 isolates (7.5%) weakly attached to conidia with 1 or
      2 yeast cells attached to a few conidia. Ten yeasts (3.4%), including 8 isolates
      of Cryptococcus laurentii, 1 isolate of Cryptococcus flavescens, and an
      unidentified species of Cryptococcus, failed to attach to conidia. All non
      attaching yeasts produced copious extracellular polysaccharide (EPS) on PDA.
      Seventeen yeast isolates did not attach to hyphal fragments of B. cinerea, R.
      solani, and S. homoeocarpa after a 1 h incubation, but attachment was observed
      after 24 h. Culture medium, but not culture age, significantly affected the
      attachment of yeast cells to conidia of B. cinerea. The 10 yeast isolates that
      did not attach to conidia when grown on agar did attach to conidia (20%-57% of
      conidia with attached yeast cells) when cultured in liquid medium. Attachment of
      the biocontrol yeast Rhodotorula glutinis PM4 to conidia of B. cinerea was
      significantly greater at 1 x 10(7) yeast cells x mL(-1) than at lower
      concentrations of yeast cells. The ability of yeast cells to attach to fungal
      conidia or hyphae appears to be a common phenotype among phylloplane yeasts.

PMID- 15714236
TI  - Phylogenetic analysis of bacterial populations in waters of the former Texcoco
      Lake, Mexico.
AB  - Molecular techniques were used to compare the compositions of the bacterial
      communities of the 2 following lagoons from the former soda Texcoco Lake, Mexico:
      the restored Facultativa lagoon and the Nabor Carrillo lagoon. Ribosomal
      intergenic spacer analysis (RISA) revealed that bacterial communities of the 2
      lagoons were different and presented a relatively low diversity. Clone libraries
      of 16S rDNA genes were constructed, and significant phylotypes were distinguished
      by restriction fragment length polymorphism (RFLP). A representative clone from
      each phylotype was partially sequenced. Molecular identification and phylogenetic
      analyses based on ribosomal sequences revealed that the Facultativa lagoon
      harbored mainly gamma- and beta-Proteobacteria, low G+C Gram-positive bacteria,
      and several members of the Halobacteriaceae family of archaea. The Nabor Carrillo
      lagoon mainly included typical halophilic and alkaliphilic low G+C Gram-positive
      bacteria, gamma-Proteobacteria, and beta-Proteobacteria similar to those found in
      other soda lakes. Several probably noncultured new bacterial species were
      detected. Three strains were isolated from the Nabor Carrillo lagoon, their
      partial 16S rDNA sequences were obtained. On this basis, they were identified as
      Halomonas magadiensis (H1), Halomonas eurihalina (H2), and Staphylococcus sciuri
      (H3). This is the first study that uses molecular techniques to investigate
      potential genetic diversity in the Texcoco lakes. In this preliminary evaluation,
      we infer the presence of alkalophilic, halophilic, or haloalkaliphilic bacteria
      potentially useful for biotechnology.

PMID- 15714237
TI  - Differentiation of group VIII Spiroplasma strains with sequences of the 16S-23S
      rDNA intergenic spacer region.
AB  - Spiroplasma species (Mollicutes: Spiroplasmataceae) are associated with a wide
      variety of insects, and serology has classified this genus into 34 groups, 3 with
      subgroups. The 16S rRNA gene has been used for phylogenetic analysis of
      spiroplasmas, but this approach is uninformative for group VIII because the
      serologically distinct subgroups generally have similarity coefficients >0.990.
      Therefore, we investigated the utility of the 16S-23S rRNA spacer region as a
      means to differentiate closely related subgroups or strains. We generated
      intergenic sequences and detailed serological profiles for 8 group VIII
      Spiroplasma strains. Sequence analyses using Maximum Parsimony, Neighbor Joining,
      and Maximum Likelihood placed the strains into 2 clades. One clade consisted of
      strains BARC 2649 and GSU5367. The other clade was divided into clusters
      containing representatives of the 3 designated group VIII subgroups (EA-1, DF-1,
      and TAAS-1) and 3 previously unclassified strains. The stability of the positions
      of the strains in various analytical models and the ability to provide robust
      support for groupings tentatively supported by serology indicates that the 16S
      23S intergenic rDNA sequence will prove useful in intragroup analysis of group
      VIII spiroplasmas.

PMID- 15714238
TI  - Isolation of sterols from the marine fungus Corollospora lacera.
AB  - Several marine fungi collected from the waters of Prince Edward Island, Canada,
      were screened for the presence of natural products exhibiting antibacterial
      activity. Both broths and mycelia of these fungi were studied using the bioassay
      guided chromatographic separation. The 4 fractions from the extract of mycelia of
      Corollospora lacera exhibited weak antibacterial activity and were analyzed
      further. From these fractions, 2 sterols (5 alpha,8 alpha-epidioxyergosterol and
      22E,24R-ergosta-7,22-diene-3beta,5 alpha,6 beta-triol) and a 3:1 mixture of
      linoleic and oleic acids were isolated. The presence of ergosterol was confirmed
      in dichloromethane extracts of mycelia of every fungus in this study and this
      sterol was isolated from the extract of mycelium of Corollospora lacera. Two
      other known compounds (5-hydroxymethylfuran-2-carbaldehyde and bis(2-ethylhexyl)
      phthalate), were isolated from the dichloromethane extract of mycelium of
      Monodictys pelagica. The phthalate was reported in the literature as a metabolite
      isolated from the fungi, but in our study it was proven to be an artifact of the
      culturing and (or) extraction procedures rather than a true fungal metabolite.

PMID- 15714239
TI  - Potential application of low-stringency single specific primer-PCR in the
      identification of Leptospira in the serum of patients with suspected
      leptospirosis.
AB  - In this study we tested the potential use of low-stringency single specific
      primer-PCR (LSSP-PCR) for genetically typing Leptospira directly from biological
      samples. Serum samples obtained from 29 patients with clinically suspected
      leptospirosis were amplified by specific PCR, using the previously selected G1
      and G2 primers. The PCR products of approximately 300 bp were subsequently used
      as a template for LSSP-PCR analysis. We were able to produce genetic signatures
      from the leptospires present in the human samples, which permitted us to make a
      preliminary identification of the infective serovar by comparing the LSSP-PCR
      profiles obtained directly from serum samples with those from reference
      leptospires. Thus, LSSP-PCR has the potential to become a useful diagnostic tool
      for identifying leptospires in biological samples without the need for bacteria
      isolation and culture.

PMID- 15714240
TI  - Deletion of the Candida albicans G-protein-coupled receptor, encoded by
      orf19.1944 and its allele orf19.9499, produces mutants defective in filamentous
      growth.
AB  - Filamentous growth of Candida albicans occurs in response to a variety of
      environmental signals. The C. albicans gene orf19.1944 and its allele orf19.9499
      are identical and are predicted to encode an 823-residue, 7-transmembrane-domain
      protein that has all the expected features of a G-protein-coupled receptor. The
      protein is 20.9% identical to the Saccharomyces cerevisiae Gpr1p receptor that
      signals both glucose availability and nitrogen limitation. Deletion of both
      copies of the gene in C. albicans abolished filamentation by colonies embedded in
      rich media (YPS, YPGal, and YPGlu), whereas mutants carrying a single copy of the
      gene were indistinguishable from the parental strain under these conditions. On
      medium containing low concentrations of ammonia (SLAD and SLAM media), surface
      colonies of both the homozygous deletion mutants and the mutants carrying a
      single copy of the gene were defective in filamentation. Serum-induced germ tube
      formation was unaffected by deletion of this gene, as was filamentation of the
      mutants growing on the surface of solid Spider medium at 37 degrees C or embedded
      in solid Spider medium at 25 degrees C. The protein encoded by orf19.1944 and
      orf19.9499 has a role in filamentation by both surface and embedded colonies,
      presumably as a sensor of environmental cues.

PMID- 15714241
TI  - Prospective, randomized trial comparing intraoperative colonic irrigation with
      manual decompression only for obstructed left-sided colorectal cancer.
AB  - BACKGROUND: This is a prospective, randomized, controlled trial comparing the
      outcome of intraoperative colonic irrigation with that of manual decompression
      for acutely obstructing colorectal cancers distal to the splenic flexure.
      METHODS: All patients admitted to our department from June 1999 to August 2002
      with obstructing left-sided colorectal cancers were recruited. Patients were
      randomized intraoperatively and were excluded if deemed unsuitable for segmental
      resection and primary anastomosis. Twenty-five patients were randomized to
      receive colonic irrigation and twenty-eight to receive manual decompression.
      Perioperative parameters and outcome including mortality and anastomotic leak
      were recorded. RESULTS: Both groups of patients were comparable in terms of
      gender and age. The time taken for mobilization, decompression, and irrigation in
      the colonic irrigation group (median, 31 minutes) was significantly longer than
      that for the manual decompression group (median, 13 minutes) (P; = 0.0005).
      However, the total time of the operation was similar for both groups. Times for
      recovery of bowel function, of wound infection, and until discharge from the
      hospital were also similar. In the manual decompression group there were two
      cases of anastomotic leak (8 percent, 2/25) requiring reoperation but none (0/24)
      in the colonic irrigation group. However, this difference was not statistically
      significant. CONCLUSION: Manual decompression of proximal colon without
      irrigation is as safe as colonic irrigation in one-stage surgical management of
      obstructing left-sided colorectal cancer.

PMID- 15714242
TI  - Use of Malone antegrade continence enema in patients with perineal colostomy
      after rectal resection.
AB  - PURPOSE: Abdominoperineal resection, with iliac colostomy, remains the gold
      standard treatment for very low-lying rectal cancer, but it alters patients'
      quality of life. Alternatives to iliac colostomy need to be experimented.
      Antegrade enemas via a cecal access (Malone operation) obtains a colonic emptying
      and improves continence for incontinent patients. Continence and quality of life
      after abdominoperineal resection and perineal colostomy associated to a Malone
      antegrade continence enema were studied. METHODS: After abdominoperineal
      resection for cancer, 18 patients had a digestive reconstruction by perineal
      colostomy and Malone antegrade continence enema. Patients performed antegrade
      enemas every 24 to 48 hours with tap water. After six months, continence
      (Cleveland Clinic score) and quality of life (Fecal Incontinence Quality of Life
      scale) were recorded. RESULTS: Morbidity was 5 percent (1 appendix necrosis). All
      patients could perform antegrade enemas by themselves. Mean continence score was
      6.41/20 (standard error, 2.31). Fecal Incontinence Quality of Life scores were:
      lifestyle 3.18/4 (standard error, 0.83); coping/ behavior 2.99/4 (standard error,
      0.83); depression/self-perception 3.11/4 (standard error, 0.83); embarrassment
      2.84/4 (standard error, 0.63). CONCLUSIONS: After abdominoperineal resection,
      Malone antegrade continence enema associated to perineal colostomy provided an
      acceptable continence. It preserved patients' body image and resulted in a
      satisfying quality of life. It could become an alternative to iliac colostomy in
      selected patients.

PMID- 15714243
TI  - The human leukocyte antigen region and colorectal cancer risk.
AB  - PURPOSE: Recently, we found a certain haplotype in the human leukocyte antigen
      Class III subregion to be associated with breast cancer. Epidemiologic studies
      have shown that breast cancer and colorectal cancer have several risk factors in
      common. In view of these studies and because polymorphisms located in the human
      leukocyte antigen III region have been found to be associated with colorectal
      cancer, we wondered whether the same region also is involved in colorectal cancer
      susceptibility. METHODS: The human leukocyte antigen region was genotyped with 14
      microsatellite markers in germline DNA from 643 colorectal cancer patients and
      841 family-based controls. Association analyses and the Haplotype Sharing
      Statistic were used to search for differences between patients and controls.
      Subgroup analyses were performed for gender, age at diagnosis, and localization
      of the tumor. RESULTS: The Haplotype Sharing Statistic analysis revealed neither
      a difference in mean haplotype sharing between all patients and controls, nor in
      any of the subgroups. The single allele, genotype, and two-locus association
      analyses for all patients and for the different subgroups did not show an
      association with colorectal cancer for the 14 microsatellite markers. Also, no
      association was observed between the tumor necrosis factor-beta polymorphism and
      colorectal cancer. CONCLUSIONS: No association was observed between commonly
      occurring haplotypes and alleles in the human leukocyte antigen region and
      colorectal cancer risk.

PMID- 15714244
TI  - Validity of pelvic autonomic nerve stimulation with intraoperative monitoring of
      bladder function following total mesorectal excision for rectal cancer.
AB  - PURPOSE: This prospective study was designed to clarify whether the results of
      the intraoperative stimulation of parasympathetic pelvic nerves performed in 31
      patients after mesorectal excision for rectal carcinoma allowed predictions in
      terms of the postoperative bladder function of the patients. METHODS: After
      monopolar stimulation of the splanchnic pelvic nerves using a constant voltage
      stimulator (Screener 3625), intravesical pressure increase was measured
      manometrically. The results were related to the postoperative residual urine
      volume, requirement of recatheterization and long-term catheterization, just as
      to the results of the validated International Prostatic Symptom Scores and the
      Quality of Life Index caused by urinary symptoms. The median follow-up period was
      nine (range, 2-14) months. RESULTS: Parasympathetic nerve stimulation was
      performed at 61 sites and results in intravesical pressure increase up to 6 cm
      water column in median. In 11 patients (33.3 percent), a negative test result was
      achieved: 5 with unilateral and 6 with bilateral pressure increases of < or = 2
      cm water column. Recatheterization was necessary in four patients, and all of
      them showed negative neuromonitoring results. Two of these patients were
      discharged with an in situ urinary bladder catheter. Postoperative increased
      residual urine volumes (> or =100 ml) resulted more frequently in the group with
      negative test results (63.6 vs. 21.1 percent; P = 0.047), and the International
      Prostatic Symptom Score and Quality of Life Index showed the worst results (9.9
      +/- 6.7 vs. 3 +/- 4.9, P = 0.021; 2.4 +/- 1.7 vs. 0.7 +/- 1.3, P = 0.021).
      CONCLUSIONS: Intraoperative neurostimulation and manometric measurement of
      bladder pressure may contribute to the identification of parasympathetic pelvic
      nerves during total mesorectal excision. This method is suitable for
      intraoperative recording of nerve preservation and therefore associated with
      postoperative bladder function.

PMID- 15714245
TI  - Sutured perineal omentoplasty after abdominoperineal resection for adenocarcinoma
      of the lower rectum.
AB  - PURPOSE: This study was designed to describe and evaluate the efficacy of sutured
      perineal omentoplasty on perineal wound healing after abdominoperineal resection
      for adenocarcinoma of the lower rectum. METHODS: Charts of patients who underwent
      abdominoperineal resection for adenocarcinoma of the rectum from June 1995 to
      December 2001 were reviewed for mortality, morbidity, and perineal healing.
      Abdominoperineal resection was accomplished according to Miles combined with
      total mesorectal excision. The omentum was pediculized on the left gastroepiploic
      artery and tightly sewn to the subcutaneous fatty tissue. The perineal skin was
      then closed primarily. RESULTS: A total of 104 patients were included in the
      study. The mean age at surgery was 65 (range, 13-91) years. The distance of the
      tumor from the anal sphincters was 0.45 +/- 0.9 mm (range, 0-50). During the
      study period, 92 patients (88 percent) had sutured perineal omentoplasty. The
      rate of primary perineal wound healing was 80 percent. Postoperative perineal
      wound complications consisted of perineal abscess in seven patients. Six of these
      patients had a sutured perineal omentoplasty (6 percent). Only four patients
      required a surgical drainage. Minor perineal suppuration occurred in four
      patients (4 percent), whereas partial perineal wound dehiscence occurred in eight
      patients (8 percent). All wounds healed completely at three months. Intestinal
      obstruction occurred in three patients (3 percent). No complication of the
      pedicled omentoplasty was observed. CONCLUSIONS: This study demonstrated that
      sutured perineal omentoplasty is possible in the majority of patients after
      abdominoperineal resection for adenocarcinoma of the lower rectum with excellent
      primary perineal wound healing.

PMID- 15714246
TI  - Loop ileostomy closure after restorative proctocolectomy: outcome in 1,504
      patients.
AB  - PURPOSE: Routine use of a temporary loop ileostomy for diversion after
      restorative proctocolectomy is controversial because of reported morbidity
      associated with its creation and closure. This study intended to review our
      experience with loop ileostomy closure after restorative proctocolectomy and
      determine the complication rates. In addition, complication rates between
      handsewn and stapled closures were compared. METHODS: Our Department Pelvic Pouch
      Database was queried and charts reviewed for all patients who had ileostomy
      closure after restorative proctocolectomy from August 1983 to March 2002.
      RESULTS: A total of 1,504 patients underwent ileostomy closure after restorative
      proctocolectomy during a 19-year period. The median length of hospitalization was
      three (range, 1-40) days and the overall complication rate was 11.4 percent.
      Complications included small-bowel obstruction (6.4 percent), wound infection
      (1.5 percent), abdominal septic complications (1 percent), and enterocutaneous
      fistulas (0.6 percent). Handsewn closure was performed in 1,278 patients (85
      percent) and stapled closure in 226 (15 percent). No significant differences in
      complication rates and length of hospitalization were found between handsewn and
      stapled closure techniques. CONCLUSIONS: Our results demonstrated that ileostomy
      closure after restorative proctocolectomy can be achieved with a low morbidity
      and a short hospitalization stay. In addition, we found that complication rates
      and length of hospitalization were similar between handsewn and stapled closures.

PMID- 15714247
TI  - Experimental model of fistula-in-ano.
AB  - PURPOSE: This study was designed to create and evaluate an experimental porcine
      model of fistula-in-ano. METHODS: Initial cadaveric dissection enabled refinement
      of the technique for fistula formation and histoanatomical study of the porcine
      anal canal. Subsequently, three surgically created fistulas were treated by seton
      drainage in each of eight male pigs (weight, 38-41 kg). After 26 days, magnetic
      resonance imaging at 1.5 Tesla was performed and setons removed under general
      anesthesia, enabling clinical and microbiologic track assessment. Two pigs were
      killed for histologic fistula track assessment. RESULTS: Histoanatomical
      assessment noted a rudimentary internal anal sphincter, together with structures
      resembling anal glands. Artificial fistulas persisted during seton drainage and
      were more often associated with fecal than skin-derived organisms compared with
      both perineal and anal canal swabs (P = 0.002). All six fistulas assessed
      histologically had a lumen, and abundant surrounding granulation tissue similar
      to that seen in human fistula-in-ano. Epithelialization was not evident in any
      track. Fistulas were visualized as high signal tracks using magnetic resonance
      imaging. CONCLUSIONS: Porcine anal anatomy resembles that of humans, and an
      experimental model proved suitable when assessed by magnetic resonance imaging,
      microbiology, and histologically, which demonstrated abundant granulation tissue.
      This model could be further used to investigate fistula treatments.

PMID- 15714248
TI  - Long-term treatment of high intestinal output syndrome with budesonide in
      patients with Crohn's disease and ileostomy.
AB  - PURPOSE: In a previous, controlled study, it was shown that orally administered
      budesonide increases the absorptive capacity of the intestinal mucosa in patients
      with ileostomies caused by Crohn's disease. This open, nonrandomized study was
      designed to analyze this functional, not inflammation-dependent steroid-effect in
      the long-term course comparing exposure, withdrawal, and reexposure. METHODS:
      Phase 1: 23 patients without inflammatory activity of the disease received oral
      budesonide (3 mg t.i.d.) for at least four weeks (36.7 weeks; standard deviation,
      45.3 weeks) because of high intestinal output syndrome. Phase 2: Medication was
      stopped for four weeks. Phase 3: Medication as in Phase 1. In each phase the
      weight of the ileostomy bags was measured with a spring balance before emptying
      and documented in a diary. Mean values per day and per week were calculated and
      the differences statistically evaluated by the Wilcoxon-(Pratt)-test. RESULTS:
      Comparing the last week of Phase 1 to first week of Phase 2, a significant (P <
      0.0001) increase of the intestinal output (295 g; standard deviation, 313 g) was
      observed after omitting budesonide. In contrast, comparing the last week of Phase
      2 to Phase 3, a significant (P < 0.0001) decrease of the intestinal output by
      323.7 g (standard deviation, 322.2 g) was noticed reaching the same level as in
      Phase 1. CONCLUSIONS: These data show that the functional, inflammation
      independent effect of budesonide on the intestinal mucosa is strongly correlated
      to the administration of the drug and may be maintained long-term. These results
      should be confirmed by a larger number of patients.

PMID- 15714249
TI  - Pelvic sepsis after extended Hartmann's procedure.
AB  - PURPOSE: An extended Hartmann's procedure is occasionally useful in rectal
      resections, because anastomotic, perineal, and functional problems are
      eliminated. This study was designed to examine the occurrence of pelvic sepsis
      after this procedure and identify possible risk factors. METHODS: Medical records
      were available for 163 patients (89 females) undergoing rectal resection with
      colostomy and closure of the rectal remnant. Information about pelvic sepsis and
      possible risk factors was obtained by review of the medical records. RESULTS:
      Pelvis sepsis developed in 31 of 163 patients (18.6 percent). When the rectum had
      been transected <2 cm above the pelvic floor, 24 of 73 patients (32.9 percent)
      developed an abscess in contrast to 7 of 90 (7.8 percent) after higher
      transsection (P = 0.0001). Other risk factors were male gender and missing foot
      pulses. Only 61 percent of pelvic abscesses healed after a median of 59 days,
      leaving 39 percent unhealed after an observation period of 277 (range, 20-1,643)
      days. CONCLUSIONS: Surgical alternatives should be considered to an extended
      Hartmann's procedure when the level of transsection is <2 cm above the pelvic
      floor, particularly in males.

PMID- 15714250
TI  - Indications of endoscopic polypectomy for rectal carcinoid tumors and clinical
      usefulness of endoscopic ultrasonography.
AB  - PURPOSE: This study was designed to define the indications of endoscopic
      polypectomy for rectal carcinoid tumors and evaluate the diagnostic value of
      endoscopic ultrasonography. METHODS: A total of 66 rectal carcinoid tumors
      treated at our hospital were analyzed histopathologically to clarify risk factors
      for metastasis. The depth of invasion was determined for 52 lesions examined by
      endoscopic ultrasonography, and the value of endoscopic ultrasonography for
      deciding whether a lesion is indicated for endoscopic polypectomy was assessed.
      RESULTS: None of the 57 lesions measuring < or = 10 mm in diameter invaded the
      muscularis propria or had metastasis. Of nine lesions with a diameter of > or =
      11 mm, five invaded the muscularis propria and four had metastasis. A central
      depression was found in three of the lesions with metastasis. The depth of
      invasion of 49 lesions examined by endoscopic ultrasonography was limited to the
      submucosa; 3 lesions invaded the muscularis propria. The depth of invasion of all
      lesions was correctly diagnosed by endoscopic ultrasonography. Ninety-six percent
      of the lesions that had submucosal invasion with narrowing of the upper two
      thirds of the third layer (submucosa) as evaluated by endoscopic ultrasonography
      could be completely resected by endoscopic polypectomy. CONCLUSIONS: Rectal
      carcinoid tumors that satisfy the following three conditions are indicated for
      local resection, including endoscopic polypectomy: a maximum diameter of < or =
      10 mm, no invasion of the muscularis propria, and no depression or ulceration in
      the lesion. Endoscopic ultrasonography also is useful for estimating the depth of
      invasion of rectal carcinoid tumors and for determining whether endoscopic
      polypectomy is indicated.

PMID- 15714252
TI  - NMDA receptor involvement in the effects of low dose domoic acid in neonatal
      rats.
AB  - We have previously reported that neonatal rats display enhanced sensitivity to
      domoic acid relative to adults, and that perinatal injections of low doses of
      domoic acid alter early associational learning in the newborn rat. The current
      study was designed to further investigate the effects of low dose domoic acid on
      neonatal odour conditioning and to determine if the observed effects are due in
      part to an action on NMDA receptors. Groups of rat pups were conditioned to a
      novel odour on postnatal day (PND) 8, injected with 20 microg/kg domoic acid
      either alone, or in combination with the NMDA antagonist CPP (or appropriate
      controls), daily from day 8-14, re-exposed to the conditioning odour or a novel
      odour on day 9, and tested for odour preference on day 13 using a standard 3
      choice paradigm. Results indicated that rats treated with domoic acid spent
      significantly more time over the conditioning odour than did saline-treated rats
      when tested on PND 13. This effect was antagonized by concomitant injection of
      CPP, indicating an involvement of NMDA receptors in the actions of DOM in this
      paradigm. Rats injected with either saline or CPP alone showed the opposite
      effect, i.e. a preference for the alternate odour. The results indicate that a
      very low dose of DOM produces a conditioned odour preference in neonatal rats and
      that this effect is due in part to NMDA receptor involvement, thereby emphasizing
      a role for both kainate and NMDA glutamate receptors in implicit memory.

PMID- 15714253
TI  - Nefopam inhibits calcium influx, cGMP formation, and NMDA receptor-dependent
      neurotoxicity following activation of voltage sensitive calcium channels.
AB  - Nefopam hydrochloride is a potent non sedative benzoxazocine analgesic that
      possesses a profile distinct from that of anti-inflammatory drugs. Previous
      evidence suggested a central action of nefopam but the detailed mechanism remains
      unclear. We have investigated the actions of nefopam on voltage sensitive calcium
      channels and calcium-mediated pathways. We found that nefopam prevented N-methyl
      D-aspartate (NMDA)-mediated excitotoxicity following stimulation of L-type
      voltage sensitive calcium channels by the specific agonist BayK8644. Nefopam
      protection was concentration-dependent. 47 muM nefopam provided 50% protection
      while full neuroprotection was achieved at 100 muM nefopam. Neuroprotection was
      associated with a 73% reduction in the BayK8644-induced increase in intracellular
      calcium concentration. Nefopam also inhibited intracellular cGMP formation
      following BayK8644 in a concentration-dependent manner, 100 muM nefopam providing
      full inhibition of cGMP synthesis and 58 muM allowing 50% cGMP formation. Nefopam
      reduced NMDA receptor-mediated cGMP formation resulting from the release of
      glutamate following activation of channels by BayK8644. Finally, we also showed
      that nefopam effectively reduced cGMP formation following stimulation of cultures
      with domoic acid, while not providing neuroprotection against domoic acid. Thus,
      the novel action of nefopam we report here may be important both for its central
      analgesic effects and for its potential therapeutic use in neurological and
      neuropsychiatric disorders involving an excessive glutamate release.

PMID- 15714254
TI  - Calcium accumulation in neurites and cell bodies of rat cerebellar granule cells
      in culture: effects on GABA(A) receptor function.
AB  - Accumulation of calcium in rat cerebellar granule cells in culture was studied by
      two photon laser scanning microscopy. Depolarizations by high extracellular
      potassium induced short-lived increases in calcium in both cell bodies and
      neurites. However, although the increase in neurites subsided completely after
      the initial peak, in cell bodies there was a persistent plateau until the high
      potassium stimulus was removed. On the contrary, the calcium signal due to NMDA
      receptors activation was persistent in both cell bodies and neurites and remained
      until the agonist was present. The nature of these calcium signals provides an
      interpretation key for the effects of NMDA receptors activation on GABA(A)
      receptors. In particular, the persistent calcium increase in neurites may explain
      the decrease in GABA activated chloride currents which are related to activation
      of dendritic/synaptic GABA(A) receptors.

PMID- 15714255
TI  - Genomics and variation of ionotropic glutamate receptors: implications for
      neuroplasticity.
AB  - We used two approaches to identify sequence variants in ionotropic glutamate
      receptor (IGR) genes: high-throughput screening and resequencing techniques, and
      "information mining" of public (e.g. dbSNP, ENSEMBL) and private (i.e. Celera
      Discovery System) sequence databases. Each of the 16 known IGRs is represented in
      these databases, their positions on a canonical physical map are established.
      Comparisons of mouse, rat, and human sequences revealed substantial conservation
      among these genes, which are located on different chromosomes but found within
      syntenic groups of genes. The IGRs are members of a phylogenetically ancient gene
      family, sharing similarities with glutamate-like receptors in plants. Parsimony
      analysis of amino acid sequences groups the IGRs into three distinct clades based
      on ligand-binding specificity and structural features, such as the channel pore
      and membrane spanning domains. A collection of 38 variants with amino acid
      changes was obtained by combining screening, resequencing, and informatics
      approaches for several of the IGR genes. This represents only a fraction of the
      sequence variation across these genes, but in fact these may constitute a large
      fraction of the common polymorphisms at these genes and these polymorphisms are a
      starting point for understanding the role of these variants in function.
      Genetically influenced human neurobehavioral phenotypes are likely to be linked
      to IGR genetic variants. Because ionotropic glutamate receptor activation leads
      to calcium entry, which is fundamental in brain development and in forms of
      synaptic plasticity essential for learning and memory and is essential for
      neuronal survival, it is likely that sequence variants in IGR genes may have
      profound functional roles in neuronal activation and survival mechanisms.

PMID- 15714256
TI  - Modulation of ventral pallidal dopamine and glutamate release by the intravenous
      anesthetic propofol studied by in vivo microdialysis.
AB  - The intravenous anesthetic propofol is reported to have various psychological
      side effects as hallucinations, sexual disinhibition, or euphoria. Hedonic and
      rewarding states like these are modulated by the dopaminergic system in the
      nucleus accumbens, prefrontal cortex and also in the ventral pallidum and by the
      glutamatergic system in the neocortex and limbic system. In the present study,
      propofol was administered either alone or in combination with the GABAA receptor
      antagonist bicuculline via reverse microdialysis into the ventral pallidum of
      freely moving rats. Dialysis fractions were taken every 20 min and analyzed for
      dopamine and glutamate using high performance liquid chromatography. Application
      of propofol decreased dopamine levels in the ventral pallidum. This effect seems
      to be mainly mediated through GABAA receptors, since it was compensated by the
      GABAA receptor antagonist bicuculline. Propofol and propofol plus bicuculline
      exerted no effect on glutamate release in this brain region. The reduced dopamine
      release in ventral pallidum was most probably mediated through a GABAergic
      feedback loop from the ventral pallidum via the nucleus accumbens to the
      dopaminergic neurons of the ventral tegmental area or by long loop feedback. As
      an increase but not a decrease of dopamine release in the ventral pallidum is
      involved in hedonic and rewarding properties, similar symptoms induced by
      propofol seem to be unrelated to an action of propofol in the ventral pallidum.

PMID- 15714257
TI  - A rat model of neurolathyrism: repeated injection of L: -beta-ODAP induces the
      paraparesis of the hind legs.
AB  - Neurolathyrisim is a motor neuron disease characterized by spastic paraparesis in
      the hind legs, and is caused by grass pea, Lathyrus sativus, which contains the
      excitotoxic amino acid, 3-N-oxalyl-L: -2,3-diaminopropanoic acid (L: -beta-ODAP),
      an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type
      glutamatergic receptor agonist. In an attempt to make a useful model of this
      disease, the CNS distribution and toxicity of L: -beta-ODAP was studied in rat
      neonates after parenteral administration. L: -beta-ODAP was detected in the
      spinal cord as well as in the pons/medulla oblongata, though only small amounts
      in the latter. Repeated injection of L: -beta-ODAP resulted in rats with
      paraparesis of the legs, though at a low incidence rate of 0.032. These paralyzed
      rats displayed the severe atrophy of the ventral root of the lumbar cord as well
      as degenerations of motor neuron. The rats were useful models for the study of
      motor neuron degeneration in the spinal cord.

PMID- 15714258
TI  - Effect of chronic glutamate administration to pregnant rats during gestation on
      metabotropic glutamate receptors from mothers and full-term fetuses brain.
AB  - Chronic glutamate treatment during gestational period caused a significant
      decrease in total metabotropic glutamate receptors (mGluR) number. Similar
      results were observed on the steady-state level of mGlu(1) receptor detected by
      immunoblotting assays, suggesting that this is the main receptor subtype
      modulated by agonist exposure. Furthermore, no variations on mRNA coding mGlu(1)
      receptor were found, suggesting post-transcriptional modulation as a possible
      mechanism of the lost of receptor detected at the membrane surface. On the other
      hand, western-blotting to determine level of G(q/11) protein and phospholipase C
      beta(1) revealed a significant decrease of both proteins in mothers brain. This
      decrease was associated with significant variation in glutamate and DHPG
      stimulated phospholipase C activity. No significant differences on mGluR
      transduction pathway components were observed in fetuses brain. These results
      suggest that glutamate intake during pregnancy causes a down-regulation of
      different proteins involved in glutamate response mediated by mGluR only in
      mothers brain without significantly affecting fetuses brain.

PMID- 15714259
TI  - Fracture risk in patients with prostate cancer on androgen deprivation therapy.
AB  - Although a decrease in bone mass is a well-known side effect of hormone therapy
      for prostate carcinoma, its clinical significance is unclear, as there is only
      scanty information about the incidence of fractures. Therefore, the aim of this
      study was to determine the risk of non-metastatic fractures in patients with
      prostate cancer undergoing androgen deprivation therapy. We performed a
      retrospective cohort study that comprised 288 patients with cancer who were
      subjected to androgen deprivation therapy (ADT). All were given LHRH agonists,
      and most of them also received peripheral androgen receptor blockers. The results
      were compared with a control group of 300 men that were not receiving ADT. The
      incidence rates of peripheral and vertebral fractures in the group of men on ADT
      were 1.9 and 0.8 per 100 patient-years, respectively. Incidence rates in the
      control group were 0.5 and 0.2, respectively. In the whole study group, 35
      patients had at least one fracture during follow-up (25 on ADT, ten controls).
      Thus, the number of patients with at least one fracture was significantly higher
      in the group on ADT (P = 0.001 by the log-rank test). The unadjusted risk ratio
      was 4.2 (CI 2.0-8.9). A similar value (risk ratio 3.6; CI 1.6-7.7, P = 0.001) was
      found after it was adjusted for other factors, such as age or prior fractures.
      Therefore, ADT is associated with a fourfold increase in the incidence rate of
      both peripheral and vertebral fractures. Although the absolute incidence remains
      relatively small, preventive measures should be considered for high-risk
      patients.

PMID- 15714260
TI  - Preliminary results of development of a single-mode Q-switched Nd: YAG ring laser
      at 213 nm and its application for the microsurgical dissection of retinal tissue
      ex vivo.
AB  - The Nd: YAG laser family offers wide possibilities for surgery applications in
      medicine. The radiation at 213 nm provides similar tissue effects as compared to
      193 nm excimer lasers, but offers considerable practical advantages in the
      operating room. As such, it is of considerable interest to create single-mode Q
      switched fifth harmonic Nd: YAG pulsed lasers with a high coefficient of
      efficiency and low divergence. Parameters of the ring three-mirror anisotropic
      cavity TEM00-Nd: YAG laser were calculated on the basis of the analysis of
      Gaussian beam behavior in the three-mirror ring cavity, with one convex spherical
      mirror and one intracavity positive lens. On the hand of numerical calculations a
      prototype of a single-mode Q-switched Nd: YAG-213 nm laser with an output energy
      of 4 mJ and a beam divergence of 1 mrad has been developed. At a pulse repetition
      rate of 50 Hz, it has a generation efficiency in the Q-switched mode of 0,6%. A
      hollow core wave guide is used in combination with a short length of a special
      fused silica optical fiber to guide the laser beam. Full-depth dissection of
      rabbit retina ex vivo was achieved at the intensities of 0.18-0.05 J/cm2 and a
      repetition rate of 50 Hz, with a linear cutting rate of 6 mm/s. Although the
      retina was completely cut, heat necrosis of the choroid did not occur. We are
      currently in the process of testing the dissection of retinal tissue during
      retinotomy, and the formation of holes in the trabecular meshwork in glaucoma
      surgery.

PMID- 15714261
TI  - Pricing and welfare implications of parallel imports in the pharmaceutical
      industry.
AB  - In this paper we investigate the implications of permitting parallel imports of
      pharmaceuticals produced by a monopoly, from one country to another. We use a
      model where countries differ in the patients' level of co-payment for buying
      pharmaceuticals, and patients differ in the utility obtained from the consumption
      of pharmaceuticals. We show that the effects of parallel imports on total welfare
      are as follows: On the one hand, when countries differ in their health system
      only, parallel imports decrease total welfare; On the other hand, when countries
      differ in the health needs of their patients only, parallel imports enhance total
      welfare.

PMID- 15714262
TI  - The quality of mercy: social health insurance in the charitable liberal state.
AB  - This paper has two, mutually supportive purposes: (1) to show that the modern
      economic rationale for universal social health insurance is consistent with the
      classical liberal understanding of property rights; (2) to show that the writings
      of the leading liberal sages-Locke, Smith, Mill, and Hayek-are congenial to
      programs economically similar to universal social health insurance, and, in
      Hayek's cases, were specifically approving. It is hoped that these facts and
      reasonings, which are unlikely to be known in toto to those who do not normally
      study across the intersection of philosophy and economics, will encourage a
      dialogue that reasserts in a non-ideological way the neglected role of property
      rights in the health economic assessment of social health insurance alternatives.

PMID- 15714263
TI  - The impact of new drug launches on longevity: evidence from longitudinal, disease
      level data from 52 countries, 1982-2001.
AB  - We perform an econometric analysis of the effect of new drug launches on
      longevity, using data from the IMS Health Drug Launches database and the WHO
      Mortality Database. Under conservative assumptions, our estimates imply that the
      average annual increase in life expectancy of the entire population resulting
      from new drug launches is about one week, and that the incremental cost
      effectiveness ratio (new drug expenditure per person per year divided by the
      increase in life-years per person per year attributable to new drug launches) is
      about $6750--far lower than most estimates of the value of a statistical life
      year.

PMID- 15714264
TI  - Lifetime cover in private insurance markets.
AB  - In the last few decades, private health insurance rates have declined in many
      countries. In countries and states with community rating, a major cause is
      adverse selection. In order to address age-based adverse selection, Australia has
      recently begun a novel approach which imposes stiff penalties for buying private
      insurance later in life, when expected costs are higher. In this paper, we
      analyze Australia's Lifetime Cover in the context of a modified version of the
      Rothschild-Stiglitz insurance model (Rothschild and Stiglitz, 1976). We allow
      empirically-based probabilities to increase by age for low-risk types. The model
      highlights the shortcomings of the Australian plan. Based on empirically-based
      probabilities of illness, we predict that Lifetime Cover will not arrest adverse
      selection. The model has many policy implications for government regulation
      encouraging long-term health coverage.

PMID- 15714265
TI  - Who really pays for health insurance? The incidence of employer-provided health
      insurance with sticky nominal wages.
AB  - This paper addresses two seeming paradoxes in the realm of employer-provided
      health insurance: First, businesses consistently claim that they bear the burden
      of the insurance they provide for employees, despite theory and empirical
      evidence indicating that workers bear the full incidence. Second, benefit
      generosity and the percentage of premiums paid by employers have decreased in
      recent decades, despite the preferential tax treatment of employer-paid benefits
      relative to wages-trends unexplained by the standard incidence model. This paper
      offers a revised incidence model based on nominal wage rigidity, in an attempt to
      explain these paradoxes. The model predicts that when the nominal wage constraint
      binds, some of the burden of increasing insurance premiums will fall on firms,
      particularly small companies with low-wage employees. In response, firms will
      reduce employment, decrease benefit generosity, and require larger employee
      premium contributions. Using Current Population Survey data from 2000-2001, I
      find evidence for this kind of wage rigidity and its associated impact on the
      employment and premium contributions of low-wage insured workers during a period
      of rapid premium growth.

PMID- 15714266
TI  - Velocity-based planning of rapid elbow movements expands the control scheme of
      the equilibrium point hypothesis.
AB  - According to the equilibrium point hypothesis of voluntary motor control, control
      action of muscles is not explicitly computed, but rather arises as a consequence
      of interaction between moving equilibrium position, current kinematics and
      stiffness of the joint. This approach is attractive as it obviates the need to
      explicitly specify the forces controlling limb movements. However, many debatable
      aspects of this hypothesis remain in the manner of specification of the
      equilibrium point trajectory and muscle activation (or its stiffness), which
      elicits a restoring force toward the planned equilibrium trajectory. In this
      study, we expanded the framework of this hypothesis by assuming that the control
      system uses the velocity measure as the origin of subordinate variables scaling
      descending commands. The velocity command is translated into muscle control
      inputs by second order pattern generators, which yield reciprocal command and
      coactivation commands, and create alternating activation of the antagonistic
      muscles during movement and coactivation in the post-movement phase,
      respectively. The velocity command is also integrated to give a position command
      specifying a moving equilibrium point. This model is purely kinematics-dependent,
      since the descending commands needed to modulate the visco-elasticity of muscles
      are implicitly given by simple parametric specifications of the velocity command
      alone. The simulated movements of fast elbow single-joint movements corresponded
      well with measured data performed over a wide range of movement distances, in
      terms of both muscle excitations and kinematics. Our proposal on a synthesis for
      the equilibrium point approach and velocity command, may offer some insights into
      the control scheme of the single-joint arm movements.

PMID- 15714267
TI  - The role of distal dendritic gap junctions in synchronization of mitral cell
      axonal output.
AB  - One of the first and most important stages of odor processing occurs in the
      glomerular units of the olfactory bulb and most likely involves mitral cell
      synchronization. Using a detailed model constrained by a number of experimental
      findings, we show how the intercellular coupling mediated by intraglomerular gap
      junctions (GJs) in the tuft dendrites could play a major role in sychronization
      of mitral cell action potential output in spite of their distal dendritic
      location. The model suggests that the high input resistance and active properties
      of the fine tuft dendrites are instrumental in generating local spike
      synchronization and an efficient forward and backpropagation of action potentials
      between the tuft and the soma. The model also gives insight into the
      physiological significance of long primary dendrites in mitral cells, and
      provides evidence against the use of reduced single compartmental models to
      investigate network properties of cortical pyramidal neurons.

PMID- 15714268
TI  - Dynamic properties of regulatory motifs associated with induction of three
      temporal domains of memory in aplysia.
AB  - A model was developed to examine dynamical properties of regulatory motifs
      correlated with different temporal domains of memory. The model represents short
      , intermediate-, and long-term phases of protein kinase A (PKA) activation, which
      appear related to corresponding phases of facilitation of the Aplysia
      sensorimotor synapse. The model also represents phosphorylation of the
      transcription factor CREB1 by PKA and consequent induction of the immediate-early
      gene Aplysia ubiquitin hydrolase (Ap-uch), which is essential for long-term
      synaptic facilitation (LTF). Simulations suggest mechanisms responsible for
      differing profiles of synaptic facilitation following massed vs. spaced exposures
      to 5-HT, and suggest a novel regulatory motif (gated positive feedback) is
      important for LTF. Simulations suggest zero-order ultrasensitivity may underlie a
      requirement of a threshold number of exposures to 5-HT for LTF induction. The
      model makes predictions for the dynamics of PKA activation and Ap-uch induction
      when MAP kinase is activated, or when repression of Ap-uch is relieved by
      inhibiting the transcription factor CREB2. This model may therefore be useful for
      understanding processes underlying memory formation in Aplysia and other systems.

PMID- 15714269
TI  - A controlled attractor network model of path integration in the rat.
AB  - Cells in several areas of the hippocampal formation show place specific firing
      patterns, and are thought to form a distributed representation of an animal's
      current location in an environment. Experimental results suggest that this
      representation is continually updated even in complete darkness, indicating the
      presence of a path integration mechanism in the rat. Adopting the Neural
      Engineering Framework (NEF) presented by Eliasmith and Anderson (2003) we derive
      a novel attractor network model of path integration, using heterogeneous spiking
      neurons. The network we derive incorporates representation and updating of
      position into a single layer of neurons, eliminating the need for a large
      external control population, and without making use of multiplicative synapses.
      An efficient and biologically plausible control mechanism results directly from
      applying the principles of the NEF. We simulate the network for a variety of
      inputs, analyze its performance, and give three testable predictions of our
      model.

PMID- 15714270
TI  - A continuous attractor network model without recurrent excitation: maintenance
      and integration in the head direction cell system.
AB  - Motivated by experimental observations of the head direction system, we study a
      three population network model that operates as a continuous attractor network.
      This network is able to store in a short-term memory an angular variable (the
      head direction) as a spatial profile of activity across neurons in the absence of
      selective external inputs, and to accurately update this variable on the basis of
      angular velocity inputs. The network is composed of one excitatory population and
      two inhibitory populations, with inter-connections between populations but no
      connections within the neurons of a same population. In particular, there are no
      excitatory-to-excitatory connections. Angular velocity signals are represented as
      inputs in one inhibitory population (clockwise turns) or the other
      (counterclockwise turns). The system is studied using a combination of analytical
      and numerical methods. Analysis of a simplified model composed of threshold
      linear neurons gives the conditions on the connectivity for (i) the emergence of
      the spatially selective profile, (ii) reliable integration of angular velocity
      inputs, and (iii) the range of angular velocities that can be accurately
      integrated by the model. Numerical simulations allow us to study the proposed
      scenario in a large network of spiking neurons and compare their dynamics with
      that of head direction cells recorded in the rat limbic system. In particular, we
      show that the directional representation encoded by the attractor network can be
      rapidly updated by external cues, consistent with the very short update latencies
      observed experimentally by Zugaro et al. (2003) in thalamic head direction cells.

PMID- 15714271
TI  - Bursting as an effective relay mode in a minimal thalamic model.
AB  - In recent years, accumulating evidence indicates that thalamic bursts are present
      during wakefulness and participate in information transmission as an effective
      relay mode with distinctive properties from the tonic activity. Thalamic bursts
      originate from activation of the low threshold calcium cannels via a local
      feedback inhibition, exerted by the thalamic reticular neurons upon the relay
      neurons. This article, examines if this simple mechanism is sufficient to explain
      the distinctive properties of thalamic bursting as an effective relay mode. A
      minimal model of thalamic circuit composed of a retinal spike train, a relay
      neuron and a reticular neuron is simulated to generate the tonic and burst firing
      modes. The integrate-and-fire-or-burst model is used to simulate the neurons.
      After discriminating the burst events with criteria based on inter-spike
      intervals, statistical indices show that the bursts of the minimal model are
      stereotypic events. The relation between the rate of bursts and the parameters of
      the input spike train demonstrates marked nonlinearities. Burst response is shown
      to be selective to spike-silence-spike sequences in the input spike train.
      Moreover, burst events represent the input more reliably than the tonic spike in
      a considerable range of the parameters of the model. In conclusion, many of the
      distinctive properties of thalamic bursts such as stereotypy, nonlinear
      dependence on the sensory stimulus, feature selectivity and reliability are
      reproducible in the minimal model. Furthermore, the minimal model predicts that
      while the bursts are more frequent in the spike train of the off-center X relay
      neurons (corresponding to off-center X retinal ganglion cells), they are more
      reliable when generated by the on-center ones (corresponding to on-center X
      ganglion cells).

PMID- 15714272
TI  - Bipallidal haemorrhage after ethylene glycol intoxication.
AB  - Acute or subacute bipallidal lesion, an uncommon radiological feature produced by
      metabolic disorders or poisoning, has never been attributed to ethylene glycol
      (EG) intoxication. This 50-year-old Afro-Caribbean alcoholic man had unexplained
      loss of consciousness. Blood tests showed osmolar gap. Drug screening was
      positive for EG at 6.06 mmol/l. Brain CT revealed bilateral pallidal haemorrhage.
      Pallidal haematoma, which could be related to deposition of oxalate crystals
      issued from EG metabolism, should lead to toxicological screening.

PMID- 15714273
TI  - Senescence marker protein-30 (SMP30) induces formation of microvilli and bile
      canaliculi in Hep G2 cells.
AB  - Senescence marker protein-30 (SMP30) is an androgen-independent factor that
      decreases with aging. To elucidate the physiological functions of SMP30, we
      transfected human SMP30 cDNA into the human hepatoma cell line, Hep G2. These Hep
      G2/SMP30 transfectants, which stably expressed large amounts of SMP30,
      proliferated at a slower rate and synthesized less DNA than mock transfectants
      (Hep G2/pcDNA3 controls). Thus, enhanced expression of SMP30 retarded the growth
      of Hep G2/SMP30 cells. Ultrastructural studies by scanning electron microscopy
      revealed numerous microvilli covering the surfaces of Hep G2/SMP30 cells, whereas
      few microvilli appeared on control cells. Subsequently, transmission electron
      microscopy revealed that groups of Hep G2/SMP30 cells exhibited bile canaliculi
      and possessed specialized adhesion contacts, such as tight junctions and
      desmosomes, at interplasmic membranes. However, in controls, units of only two
      cells were seen, and these lacked specialized adhesion junctions. Moesin and ZO-1
      are known to be concentrated in microvilli and at tight junctions, respectively.
      Double-immunostaining was performed to examine whether moesin and ZO-1 were
      expressed in bile canaliculi with microvilli at the apical regions of Hep
      G2/SMP30 cells. The intensity of moesin and ZO-1 staining in the contact regions
      of each cell was markedly higher in Hep G2/SMP30 than in control cells. Moreover,
      moesin stained more interior areas, which corresponded to the microvilli of bile
      canaliculi. Clearly, bile canaliculi with microvilli formed at the apical ends of
      Hep G2/SMP30 cells. These results indicate that SMP30 has an important
      physiological function as a participant in cell-to-cell interactions and imply
      that the down-regulation of SMP30 during the aging process contributes to the
      deterioration of cellular interactivity.

PMID- 15714274
TI  - Increased uptake of folate conjugates by activated macrophages in experimental
      hyperlipemia.
AB  - In the pathogenesis of atherosclerosis, macrophages become activated and play a
      crucial role in plaque formation. Activated synovial macrophages have recently
      been shown to express receptors for folic acid. We have determined whether
      activated macrophages also over-express folate receptor (FR) in atherosclerosis.
      Most normal cells express little or no FR, and, if FR is present on activated
      macrophages, folate-linked compounds and drugs could be selectively targeted to
      those cells that do express FR. To evaluate the FR on macrophages of
      atherosclerotic animals, golden Syrian hamsters were maintained on a
      hyperlipidemic diet until extensive vascular lesions had developed. Uptake of
      folic acid conjugated to fluorescent tags was then examined in tissue fragments
      from lesion-prone areas, and peritoneal activated macrophages were harvested from
      the same animals. Spectrofluorimetric and fluorescence microscopic analyses
      showed a significantly greater uptake of folate-conjugates by peritoneal
      macrophages of hyperlipidemic hamsters compared with those of hamsters fed a
      normal or folate-deficient diet. Systemically administered folate-fluorescent
      conjugates were found to accumulate as bright spots in protrusions of
      atherosclerotic plaques populated by macrophages, whereas a low level of
      fluorescence was detected uniformly dispersed across the lesion. The uptake of
      the folate conjugate by U937 macrophage cells grown in a high-lipid culture
      medium was significantly higher than in controls. Our data thus indicate that
      hyperlipidemic conditions induce an increased uptake of folate attributable to
      the over-expression of FRs on activated macrophages. This increase in FR
      expression can be exploited to deliver folate-linked compounds selectively to
      atherosclerotic lesions.

PMID- 15714275
TI  - Angiopoietin-1 promotes neurite outgrowth from dorsal root ganglion cells
      positive for Tie-2 receptor.
AB  - The effects of vascular factors on the nervous system are still poorly
      investigated. Angiopoietin-1 (Ang-1), an endothelial cell growth factor with
      influences on blood vessel stabilization, has been recently reported to prevent
      apoptosis in a neuroblastoma cell line via a pathway dependent on Tie-2 receptor.
      The present study focuses on the effect of Ang-1 on cultured dorsal root ganglion
      (DRG) cells isolated from 1-day-old rats. Three-day-old DRG cultures were exposed
      to Ang-1 treatment under serum-free condition for another 5 days and stained with
      antibodies against neurofilament (NF) 200 protein. Neurite length and density
      increased compared with those of controls. Double-immunofluorescence staining
      demonstrated the co-localization of the Tie-2 receptor in some NF-200-positive
      perikarya. The reverse transcription/polymerase chain reaction technique
      identified Tie-2 receptor mRNA in intact DRG and in Ang-1-stimulated DRG cell
      cultures, but not in a Schwann cell line or in primary astrocyte cultures.
      Western blotting confirmed that the expression of NF 68 protein in cultures
      treated with Ang-1 or nerve growth factor was higher than that in cultures
      treated with medium alone. When the Tie-2 receptor was blocked with anti-Tie-2
      receptor antibody, neurite outgrowth was severely impeded. Induction of trkA
      receptor protein expression was observed to be dependent on the presence of Tie-2
      receptors. We conclude that Ang-1 promotes neurite outgrowth from DRG cells
      positive for Tie-2 receptor. The signalling pathway appears to involve
      transactivation of the trkA receptor.

PMID- 15714276
TI  - Cyclic AMP alleviates endoplasmic stress and programmed cell death induced by
      lipopolysaccharides in human endothelial cells.
AB  - The possible protection provided by enhancement of the cAMP signal in the process
      of lipopolysaccharide (LPS)-induced endothelial cell death has been addressed,
      with special emphasis on the endoplasmic initiation of caspase-12-mediated
      apoptosis. Human umbilical vein endothelial cells were challenged with LPS to
      reduce viability after 12 h to less than 20% that of the control. Cell death was
      preceded by ultrastructural disintegration at the endoplasmic reticulum, PERK
      phosphorylation, degradation of caspase-12-like protein and cleavage of caspase
      9, resulting in apoptosis through the activation of caspase 3. Treatment with a
      cell-permeable cAMP analogue led to a dose-dependent reduction of cell death over
      time, mitigated endoplasmic reticulum disturbances, reduced phosphorylation of
      PERK, and the degradation of caspases 12, 9 and 3. The selective inhibition of
      caspase 9 completely supplanted the anti-apoptotic effects obtained by cAMP,
      while being without any influence on caspase 12 degradation. The data suggest
      that cAMP positively modulates early endoplasmic alterations and caspase
      activation in LPS-induced apoptosis.

PMID- 15714277
TI  - Insulin-like growth factor-I stimulates cell proliferation in the outer layer of
      Hertwig's epithelial root sheath and elongation of the tooth root in mouse molars
      in vitro.
AB  - To elucidate the mechanism of root formation in tooth development, we examined
      the role of insulin-like growth factor I (IGF-I) on early root formation in
      mandibular first molar teeth from 5-day-old mice. Immunohistochemistry revealed
      the specific localization of the IGF-I receptor in Hertwig's epithelial root
      sheath (HERS) in the tooth root. The effect of IGF-I on root development,
      especially on HERS, was subsequently examined in vitro. The control culture
      showed normal development of HERS and the periodontium, resembling that in vivo.
      However, the presence of 100 ng/ml IGF-I resulted in elongation of HERS and
      increased cell proliferation in its outer layer. These effects were negated by
      the addition of antibodies specific for IGF-I. Thus, we propose that IGF-I is
      involved in early root formation by regulating the mitotic activity in the outer
      layer of HERS.

PMID- 15714278
TI  - Method for the generation and cultivation of functional three-dimensional mammary
      constructs without exogenous extracellular matrix.
AB  - During puberty, pregnancy, lactation and post-lactation, breast tissue undergoes
      extensive remodelling and the disruption of these events can lead to cancer. In
      vitro studies of mammary tissue and its malignant transformation regularly employ
      mammary epithelial cells cultivated on matrigel or floating collagen rafts. In
      these cultures, mammary epithelial cells assemble into three-dimensional
      structures resembling in vivo acini. We present a novel technique for generating
      functional mammary constructs without the use of matrix substitutes.

PMID- 15714279
TI  - Early innate immune response and redistribution of inflammatory cells in the bony
      fish gilthead seabream experimentally infected with Vibrio anguillarum.
AB  - An obvious difference between the immune system of fish and mammals is that fish
      lack both bone marrow and lymph nodes; in their place, the head-kidney acts as a
      major haematopoietic and lymphoid organ in adult fish, whereas the thymus, spleen
      and mucosa-associated lymphoid tissues are common to both fish and mammals. This
      suggests that differences exist in antigen presentation and naive lymphocyte
      stimulation, a prerequisite for the initiation of adaptive immune responses.
      Intraperitoneal injection of the bony fish gilthead seabream (Sparus aurata L.)
      with intact Vibrio anguillarum, as a particulate bacterial antigen, results in
      the mobilisation of head-kidney leucocytes to the peritoneal cavity and priming
      of their respiratory burst activity. We have also observed the rapid infiltration
      of acidophilic granulocytes, which are leucocytes functionally equivalent to
      mammalian neutrophils, into the spleen. These cells may be involved in antigen
      capture and transport to the spleen, since an apparent association between
      mobilised acidophilic granulocytes, bacterial antigens and proliferating
      lymphocytes has been seen in this organ. Collectively, these results suggest
      that, in addition to being actively involved in bacterial clearance, fish
      phagocytic granulocytes play a role in the initiation and support of the adaptive
      immune response.

PMID- 15714280
TI  - Changes in retinal neuronal populations in the DBA/2J mouse.
AB  - DBA/2J (D2) mice develop a form of progressive pigmentary glaucoma with
      increasing age. We have compared retinal cell populations of D2 mice with those
      in control C57BL/6J mice to provide information on retinal histopathology in the
      D2 mouse. The D2 mouse retina is characterized by a reduction in retinal
      thickness caused mainly by a thinning of the inner retinal layers.
      Immunocytochemical staining for specific inner retinal neuronal markers, viz.,
      calbindin for horizontal cells; protein kinase C (PKC) and recoverin for bipolar
      cells, glycine, gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT),
      and nitric oxide synthase (NOS) for amacrine cells, and osteopontin (OPN) for
      ganglion cells, was performed to detect preferentially affected neurons in the D2
      mouse retina. Calbindin, PKC, and recoverin immunoreactivities were not
      significantly altered. Amacrine cells immunoreactive for GABA, ChAT, and OPN were
      markedly decreased in number, whereas NOS-immunoreactive amacrine cells increased
      in number. However, no changes were observed in the population of glycine
      immunoreactive amacrine cells. These findings indicate a significant loss of
      retinal ganglion and some amacrine cells, whereas glycinergic amacrine cells,
      horizontal, and bipolar cells are almost unaffected in the D2 mouse. The
      reduction in amacrine cells appears to be attributable to a loss of GABAergic and
      particularly cholinergic amacrine cells. The increase in nitrergic neurons with
      the consequent increase in NOS and NO may be important in the changes in the
      retinal organization that lead to glaucomain D2 mice. Thus, the D2 mouse retina
      represents a useful model for studying the pathogenesis of glaucoma and
      mechanisms of retinal neuronal death and for evaluating neuroprotection
      strategies.

PMID- 15714281
TI  - Transferrin recycling and dextran transport to lysosomes is differentially
      affected by bafilomycin, nocodazole, and low temperature.
AB  - The effects of bafilomycin, nocodazole, and reduced temperature on recycling and
      the lysosomal pathway have been investigated in various cultured cell lines and
      have been shown to vary dependent on the cell type examined. However, the way in
      which these treatments affect recycling and transport to lysosomes within the
      same cell line has not been analyzed. In the current study, we used fluorophore
      labeled transferrin and dextran as typical markers for the recycling and the
      lysosomal pathways, respectively, to explore the morphology and the
      intravesicular pH of endocytic compartments in HeLa cells. The V-ATPase inhibitor
      bafilomycin selectively inhibited the transport of marker destined for lysosomal
      degradation in early endosomes, whereas the transport of transferrin to the
      perinuclear recycling compartment (PNRC) still occurred. The kinetics of
      transferrin acidification was found to be biphasic, indicative of fast and slow
      recycling pathways via early endosomes (pH 6.0) and PNRC (pH 5.6), respectively.
      Furthermore, the disruption of microtubules by nocodazole blocked the transport
      of transferrin to the PNRC in early endosomes and of lysosome-directed marker
      into endosomal carrier vesicles. In contrast, incubation at 20 degrees C affected
      the lysosomal pathway by causing retention of internalized dextran in late
      endosomes and a delay in transferrin recycling. Taken together, these data
      clearly demonstrate, for the first time, that the transferrin recycling pathway
      and transport of endocytosed material to lysosomes are differentially affected by
      bafilomycin, nocodazole, and low temperature in HeLa cells. Consequently, these
      treatments can be applied to investigate whether internalized macromolecules such
      as viruses follow a recycling or degradative pathway.

PMID- 15714282
TI  - The location and phenotype of proliferating neural-crest-derived cells in the
      developing mouse gut.
AB  - Neural crest cells that originate in the caudal hindbrain migrate into and along
      the developing gastrointestinal tract to form the enteric nervous system. While
      they are migrating, neural-crest-derived cells are also proliferating. Previous
      studies have shown that the expression of glial-derived neurotrophic factor
      (GDNF) and endothelin-3 is highest in the embryonic caecum, and that GDNF alone
      or in combination with endothelin-3 promotes the proliferation of enteric neural
      crest-derived cells in vitro. However, whether neural proliferative zones, like
      those in the central nervous system, are found along the developing gut is
      unknown. We used a fluorescent nucleic acid stain to identify dividing cells or
      BrdU labelling (2 h after administration of BrdU to the mother), combined with
      antibodies specific to neural crest cells to determine the percentage of
      proliferating crest-derived cells in various gut regions of embryonic day 11.5
      (E11.5) and E12.5 mice. The rate of proliferation of crest-derived cells did not
      vary significantly in different regions of the gut (including the caecum) or at
      different distances from the migratory wavefront of vagal crest-derived cells.
      The phenotype of mitotic enteric crest-derived cells was also examined. Cells
      expressing the pan-neuronal markers, neurofilament-M and Hu, or the glial marker,
      S100b, were observed undergoing mitosis. However, no evidence was found for
      proliferation of cells expressing neuron-type-specific markers, such as nitric
      oxide synthase (at E12.5) or calcitonin gene-related peptide (at E18.5). Thus,
      for enteric neurons, exit from the cell cycle appears to occur after the
      expression of pan-neuronal proteins but prior to the expression of markers of
      terminally differentiated neurons.

PMID- 15714283
TI  - Neuropeptide co-localisation in the lepidopteran frontal ganglion studied by
      electron-microscopic gold-labelling immunocytochemistry.
AB  - An immunogold-labelling electron-microscopic study of the frontal ganglion of two
      noctuids, Lacanobia oleracea and Helicoverpa armigera, has been carried out with
      antisera directed against three neuropeptides; allatostatins of the Y/FXFGL-NH2
      type, Manduca sexta allatostatin (Mas-AS) and M. sexta allatotropin. The ganglion
      of both noctuids has two pairs of large peptidergic neurones with many clusters
      of electron-dense granules, one pair being situated anteriorly and the other
      posteriorly. By means of a double-labelling ("flip-flop") technique, with
      different sizes of gold particles, all possible paired combinations of the three
      different types of peptide have been visualised within granules of the anterior
      neurones, leading to the conclusion that the three peptides are co-packaged and
      co-stored in these cells. Within the posterior neurones of L. oleracea, gold
      labelling of granules is only linked to the Y/FXFGL-NH2 allatostatin antisera
      and, in contrast to the anterior cells of this species in which double gold
      labelling results in a sparse accumulation of gold particles for any one peptide
      type, single labelling gives a more intense, uniform pattern of gold particles.
      In contrast to L. oleracea, the gold-labelling pattern seen in the posterior
      neurones of H. armigera reflects the co-localisation of allatostatins of the
      Y/FXFGL-NH2 type with Mas-AS in this species. Allatotropin is absent in the
      posterior neurones of both species.

PMID- 15714284
TI  - Developmental pattern of three vesicular glutamate transporters in the rat
      superior olivary complex.
AB  - Vesicular glutamate transporters (VGLUTs) mediate the packaging of the excitatory
      neurotransmitter glutamate into synaptic vesicles. Three VGLUT subtypes have been
      identified so far, which are differentially expressed in the brain. Here, we have
      investigated the spatiotemporal distribution of the three VGLUTs in the rat
      superior olivary complex (SOC), a prominent processing center, which receives
      strong glutamatergic inputs and which lies within the auditory brainstem.
      Immunoreactivity (ir) against all three VGLUTs was found in the SOC nuclei
      throughout development (postnatal days P0-P60). It was predominantly seen in axon
      terminals, although cytoplasmic labeling also occurred. Each transporter
      displayed a characteristic expression pattern. In the adult SOC, VGLUT1 labeling
      varied from strong in the medial nucleus of the trapezoid body, lateral superior
      olive, and medial superior olive (MSO) to moderate (ventral and lateral nuclei of
      the trapezoid body) to faint (superior paraolivary nucleus). VGLUT2-ir was
      moderate to strong throughout the SOC, whereas VGLUT3 was only weakly expressed.
      These results extend previous reports on co-localization of VGLUTs in the
      auditory brainstem. As in the adult, specific features were seen during
      development for all three transporters. Intensity increases and decreases
      occurred with both VGLUT1 and VGLUT3, whereas VGLUT2-ir remained moderately high
      throughout development. A striking result was obtained with VGLUT3, which was
      only transiently expressed in the different SOC nuclei between P0 and P12. A
      transient occurrence of VGLUT1-immunoreactive terminals on somata of MSO neurons
      was another striking finding. Our results imply a considerable amount of synaptic
      reorganization in the glutamatergic inputs to the SOC and suggest differential
      roles of VGLUTs during maturation and in adulthood.

PMID- 15714285
TI  - Fibroblastic cells from human periapical granulation tissue preferentially form
      calcified matrices in decalcified boiled rat bone.
AB  - We have been studying the potential of human fibroblastic cells (HFC) from
      periapical granulation tissue to form a calcified matrix. Recently, we reported
      that inflamed periapical granulation tissue contains osteogenic cells. In the
      present study, we tested the hypothesis that HFC, cultured with decalcified bone
      (DB) of rat, might form much greater calcified matrices than with rat decalcified
      boiled bone (DBB), which was originally prepared as a negative control. HFC were
      cultured with DB or DBB in the presence or absence of 2 mM beta-glycerophosphate
      (beta-GP) and 50 microg/ml ascorbic acid. After six weeks of culture, a number of
      von Kossa-positive globular structures were unexpectedly observed inside DBB, but
      not DB. Without HFC, such structures were never seen in DBB incubated with 2 mM
      beta-GP and 50 microg/ml ascorbic acid. DB cultured with HFC under the same
      conditions did not show these structures. Electron-microscopic observation
      revealed that matrix vesicles aggregated on collagen fibrils around globular
      structures in DBB. Energy dispersive X-ray microanalysis confirmed that these
      structures were calcified matrices composed of calcium and phosphate. These
      results suggest that human periapical granulation tissue contains cells
      responsible for the formation of calcified matrices in DBB, and that DBB could
      serve as an excellent scaffold for the calcification of HFC, rather than DB.

PMID- 15714286
TI  - Hoxa3 regulates the proliferation and differentiation of the third pharyngeal
      arch mesenchyme in mice.
AB  - Genetic disruption of Hoxa3 results in bilateral defects of the common carotid
      artery, which is derived from the third branchial arch artery. The tunica media
      of the great arteries derived from the arch arteries is formed by the
      ectomesenchymal neural crest cells. To examine the etiology of the regression of
      the third arch artery, we generated Hoxa3 homozygous null mutant embryos that
      expressed a lacZ marker transgene driven by a connexin43 (Cx43): promoter in the
      neural crest cells. The expression of beta-galactosidase in these mouse embryos
      was examined by both whole-mount X-gal staining and immunohistochemistry with the
      monoclonal beta-galactosidase antibody on sections. The migration of neural crest
      cells from the neural tube to the third branchial arch was not affected in the
      Hoxa3 homozygotes. The initial formation of the third arch artery was also not
      disturbed. The artery, however, regressed at embryonic day 11.5 (E11.5), when
      differentiation of the third pharyngeal arch began. The internal and external
      carotid arteries arose from the dorsal aorta in E12.5 null mutants, which showed
      an abnormal persistence of the ductus caroticus. The third pharyngeal arch of
      wild-type mice fuses with the fourth and second arches at E12.0. In the Hoxa3
      null mutants, however, the fusion was delayed, and the hypoplastic third
      pharyngeal arch was still discerned at E12.5. Moreover, the number of
      proliferating cells in the third arch of the null mutants was small compared with
      that in the wild-type. Thus, Hoxa3 is required for the growth and differentiation
      of the third pharyngeal arch. The defective development of the third pharyngeal
      arch may induce the anomalies of the carotid artery system.

PMID- 15714287
TI  - Bilateral isokinetic training reduces the bilateral leg strength deficit for both
      old and young adults.
AB  - The bilateral limb deficit (BLD) describes the difference in maximal or near
      maximal force generating capacity of muscles when they are contracted alone and
      in combination with the contralateral muscles. This study examined the effects of
      a 6-week (three times per week) bilateral leg strength training programme on BLD
      in younger and older adults. Data were collected from 33 subjects during slow (45
      degrees /s) isokinetic knee extensions and flexions before and after the training
      programme. After training, the BLD was reduced for extension (73.3-86.9%; P <
      0.001) but not for flexion (67.5-71.2%; P = 0.13) regardless of age and gender.
      This study suggests that difficulty in recruiting all muscle units during a task
      involving bilateral activation can be improved by training, although such an
      effect appears to depend on the muscle group appreciated.

PMID- 15714288
TI  - A comparison of muscular activity during single and double mouse clicks.
AB  - Work-related musculoskeletal disorders (WMSDs) in the neck/shoulder region and
      the upper extremities are a common problem among computer workers. Occurrences of
      motor unit (MU) double discharges with very short inter-firing intervals
      (doublets) have been hypothesised as a potential additional risk for overuse of
      already exhausted fibres during long-term stereotyped activity. Doublets are
      reported to be present during double-click mouse work tasks. A few comparative
      studies have been carried out on overall muscle activities for short-term tasks
      with single types of actions, but none on occurrences of doublets during double
      versus single clicks. The main purpose of this study was to compare muscle
      activity levels of single and double mouse clicks during a long-term combined
      mouse/keyboard work task. Four muscles were studied: left and right upper
      trapezius, right extensor digitorum communis (EDC) and right flexor carpi
      ulnaris. Additionally, MU activity was analysed through intramuscular
      electromyography in the EDC muscle for a selection of subjects. The results
      indicate that double clicking produces neither higher median or 90th percentile
      levels in the trapezius and EDC muscles, nor a higher disposition for MU
      doublets, than does single clicking. Especially for the 90th percentile levels,
      the indications are rather the opposite (in the EDC significantly higher during
      single clicks in 8 of 11 subjects, P < 0.05). Although it cannot be concluded
      from the present study that double clicks are harmless, there were no signs that
      double clicks during computer work generally constitute a larger risk factor for
      WMSDs than do single clicks.

PMID- 15714289
TI  - A new device for controlled eccentric overloading in training and rehabilitation.
AB  - The aim of this work was to evaluate a device that allows for eccentric overload
      to be applied under controlled and safe conditions and it is applicable in
      exercises commonly used in training and rehabilitation. The machine contains a
      barbell, which is lowered and raised by a motor, following a predetermined
      velocity profile. It is capable of handling heavy loads (>500 kg) and is
      instrumented with a sensor to measure the velocity of the barbell and two scales
      to measure the vertical component of the ground reaction force. The velocity
      recordings of the built-in displacement sensor were found to correspond well with
      those obtained using a motion-capture system. Applying known weights on each
      scale demonstrated linearity with respect to magnitude and independence regarding
      location of application. The velocity of the barbell was found to be dependent on
      the load on the barbell and on the resisting force produced by the individual
      training in the machine. The combined man-machine reliability was tested using a
      group of habitually active males (n = 13, 28-55 years) performing squats. Peak
      voluntary resisting force and position at peak resistance were recorded on two
      occasions, showing no significant differences and a coefficient of variation of
      9% and 22%, respectively. Preliminary observations from training in the machine
      have been positive both for increasing performance in top athletes and for
      causing pain relief in patients with diffuse knee problems. The possibility of
      feedback of the force under each foot makes individual dosage of training load
      possible, which is valuable, e.g. in rehabilitation of a unilateral injury.

PMID- 15714290
TI  - Prior endurance exercise attenuates growth hormone response to subsequent
      resistance exercise.
AB  - This study examined the influence of prior endurance exercise on hormonal
      responses to subsequent resistance exercise. Ten males exercised on a cycle
      ergometer at 50% of maximal oxygen uptake for 60 min and subsequently completed a
      resistance exercise (bench and leg press, four sets at ten repetitions maximum
      with an interset rest period of 90 s). Alternatively, the subjects performed the
      protocol on a separate day with prior endurance exercise limited to 5 min. Blood
      was obtained before and after the endurance exercise, and 10, 20, and 30 min
      after the resistance exercise. Maximal isometric torque measured before and after
      endurance and resistance exercises showed no significant difference between
      trials. No significant difference was seen in the concentrations of glucose,
      lactate, testosterone, and cortisol between the trials, but free fatty acids
      (FFA) and growth hormone (GH) increased (P<0.01 and P<0.05, respectively) after
      60 min of endurance exercise. Conversely, after the resistance exercise, GH was
      attenuated by 60 min of prior exercise (P<0.05). These results indicate that the
      GH response to resistance exercise is attenuated by prior endurance exercise.
      This effect might be caused by the increase in blood FFA concentration at the
      beginning of resistance exercise.

PMID- 15714291
TI  - Nutrient intake and performance during a mountain marathon: an observational
      study.
AB  - In order to study nutrient intake of amateur runners during a mountain marathon,
      compliance with recommendations, and association with performance, an intake of
      42 participants in a Swiss mountain marathon was assessed by direct observation.
      Data on demographics, dietary preparation and race experience were obtained by
      questionnaires. Anthropometrical measures were performed before and after the
      race. Mean hourly intakes (SD) of fluid, carbohydrate, energy and sodium were 545
      (158) ml, 31 (14) g, 141 (63) kcal [or 590 (264) kJ], and 150 (203) mg
      respectively. A third of the runners drank 600 ml h(-1) or more, 52% consumed
      less than 30 g h(-1 )carbohydrates, 95% consumed less than 500 mg h(-1) sodium.
      Mean weight loss was 4 (1.5) kg; 30 runners (71%) lost over 3% body mass. Mean
      running time was 7 h 3 min (1 h 17 min). Most participants failed to meet
      nutritional recommendations. None were at risk of overhydration. Body composition
      and race experience were correlated with performance, but not nutrient intake.
      Because experienced runners are well trained, fitter, and know better their
      personal needs during such a race, it is difficult to disentangle these
      associations. As causal relationship cannot be proven with this cross-sectional
      design, non-compliance with intake recommendations requires additional
      experimental research on the impact of nutrient intake on field performance.

PMID- 15714292
TI  - Modified lay-open (incision, curettage, partial lateral wall excision and
      marsupialization) versus total excision with primary closure in the treatment of
      chronic sacrococcygeal pilonidal sinus: a prospective, randomized clinical trial
      with a complete two-year follow-up.
AB  - BACKGROUND AND AIMS: The best surgical technique for treating pilonidal sinus
      disease is controversial. The aim of this study is to compare the modified lay
      open technique with primary closure following excision with respect to operating
      time, healing time, time before return to work, morbidity rate, and recurrence
      rate. PATIENTS AND METHODS: After a pre-study power analysis, 142 patients with
      chronic sacrococcygeal pilonidal sinus were prospectively and randomly allocated,
      either to the modified lay-open group (Group A, n=73) or the primary closure
      group (Group B, n=69). In the former, incision, curettage, partial lateral wall
      excision, and marsupialization were performed. Single doses of cefazoline (1 g)
      and metronidazole (500 mg) were given intravenously 15 min before surgery to all
      patients. RESULTS: There were no differences with respect to gender, age, body
      mass index, and mean operating time between the groups. In Group A, healing
      failure and early bridging occurred in one patient each. In Group B, wound
      infection occurred in four patients, wound breakdown in three, one healing
      failure and hematoma in one patient each. Morbidity and recurrence rates were
      significantly lower in Group A (2.7 vs. 13%, P=0.028 and 1.4 vs. 17.4%, P<0.001
      respectively). The median time before return to work in Group A was significantly
      shorter than in Group B (3 [range 2--8] vs. 21 [range 14--63] days, P<0.001). The
      median healing time in Group A was significantly longer than in Group B (7 [range
      3--16] weeks vs. 2 [range 2--9] weeks; P<0.001). CONCLUSION: The results of the
      present study suggest that modified lay-open is superior to excision with primary
      closure for the surgical treatment of chronic sacrococcygeal pilonidal sinus with
      regard to morbidity and recurrence rates, and time before return to work,
      although healing time is longer.

PMID- 15714293
TI  - Recto-sigmoid polyposis revealing rectal prolapse in two young patients.

PMID- 15714294
TI  - Role of pelvicography and colpocystodefecography in diagnosis of outlet
      obstructive constipation.
AB  - AIMS: The aim was to research the changes in pelvic floor morphology and
      corresponding visceras in patients with outlet obstructive constipation (OOC).
      PATIENTS AND METHODS: Thirty-eight patients with OOC and 12 healthy volunteers
      were enrolled in this study. With simultaneous pelvicography and
      colpocystodefecography (PCCD), including pelvicography, vaginal opacification,
      voiding cystography and defecography, pelvic floor morphology was observed and
      the anorectal angle, the level of the perineum, peritoneum and bladder were
      measured. RESULTS: Thirty-seven cases of internal rectal prolapse (IRP), 5 cases
      of rectocele (RC) and 5 cases of spastic pelvic floor syndrome SPFS were
      diagnosed by PCCD. 12 IRP, 4 RC and 1 SPFS were detected by common physical
      examination. All of these were confirmed by PCCD. Moreover, PCCD found 9 pelvic
      floor hernia or peritoneoceles, 6 cystoceles, 3 descending perineum syndromes and
      10 uterine prolapses. Compared with controls, OOC patients had a significantly
      large anorectal angle during defecation, abnormal descending of the perineum at
      rest and during defecation, and a deep pouch of Douglas during defecation. Some
      patients with urinary system symptoms may have had an abnormal descent of the
      bladder during rest and defecation. CONCLUSION: Simultaneous PCCD has a higher
      positive ratio than the common physical examination in diagnosing IRP and RC, and
      provides information for the diagnosis of pelvic floor hernia or peritoneocele,
      cystocele or uterine prolapse. PCCD is helpful in the selection of a proper
      surgical procedure.

PMID- 15714295
TI  - Unique regulation of glyoxalase I activity during osmotic stress response in the
      fission yeast Schizosaccharomyces pombe: neither the mRNA nor the protein level
      of glyoxalase I increase under conditions that enhance its activity.
AB  - Glyoxalase I is a ubiquitous enzyme that catalyzes the conversion of
      methylglyoxal, a toxic 2-oxoaldehyde derived from glycolysis, to S-D
      lactoylglutathione. The activity of glyoxalase I in the fission yeast
      Schizosaccharomyces pombe was increased by osmotic stress induced by sorbitol.
      However, neither the mRNA levels of its structural gene nor its protein levels
      increased under the same conditions. Cycloheximide blocked the induction of
      glyoxalase I activity in cells exposed to osmotic stress. In addition, glyoxalase
      I activity was increased in stress-activated protein kinase-deficient mutants
      (wis1 and spc1). We present evidence for the post-translational regulation of
      glyoxalase I by osmotic stress in the fission yeast.

PMID- 15714296
TI  - Quantitative structure-activity relationship by CoMFA for cyclic urea and
      nonpeptide-cyclic cyanoguanidine derivatives on wild type and mutant HIV-1
      protease.
AB  - 3D-QSAR studies using the Comparative Molecular Field Analysis (CoMFA)
      methodology were conducted to predict the inhibition constants, K(i), and the
      inhibitor concentrations, IC90 of 127 symmetrical and unsymmetrical cyclic urea
      and cyclic cyanoguanidine derivatives containing different substituent groups
      such as: benzyl, isopropyl, 4-hydroxybenzyl, ketone, oxime, pyrazole, imidazole,
      triazole and having anti-HIV-1 protease activities. A significant cross-validated
      correlation coefficient (q2) of 0.63 and a fitted correlation coefficient r2 of
      0.70 were obtained, indicating that the models can predict the anti-protease
      activity from poorly to highly active compounds reliably. The best predictions
      were obtained for: XV643 (predicted log 1/K(i) = 9.86), a 3,5-dimethoxy-benzyl
      cyclic urea derivate (molec60, predicted log 1/K(i) = 8.57) and a benzyl cyclic
      urea derivate (molec 61, predicted log 1/IC90 = 6.87). Using the CoMFA method, we
      also predicted the biological activity of 14 cyclic urea derivatives that inhibit
      the HIV-1 protease mutants V82A, V82I and V82F. The predicted biological
      activities of the: (i) XNO63 (inhibitory activity on the mutant HIV-1 PR V82A),
      (ii) SB570 (inhibiting the mutant HIV-1 PR V82I) and also (iii) XV652 (during the
      interaction with the mutant HIV-1 PR V82F) were in good agreement with the
      experimental values.

PMID- 15714297
TI  - Chromosomal integration of sfp gene in Bacillus subtilis to enhance
      bioavailability of hydrophobic liquids.
AB  - Bacillus subtilis C9 effectively degrades aliphatic hydrocarbons up to a chain
      length of C19 and produces a lipopeptide-type biosurfactant, surfactin, yet it
      has no genetic competency. Therefore, to obtain a transformable surfactin
      producer, the sfp gene cloned from B. subtilis C9 was integrated into the
      chromosome of B. subtilis 168, a non-surfactin producer, by homologous
      recombination. The transformants reduced the surface tension of the culture broth
      from 70.0 mN/m to 28.0 mN/m, plus the surface-active compound produced by the
      transformants exhibited the same Rf value as that from B. subtilis C9 and
      authentic surfactin in a thin-layer chromatographic analysis. The integration of
      the sfp gene into the chromosome of B. subtilis 168 was confirmed by Southern
      hybridization. Like B. subtilis C9, the transformants readily degraded n
      hexadecane, although the original strain did not. It was also statistically
      confirmed that the hydrocarbon degradation of the transformants was highly
      correlated to their surfactin production by the determination of the correlation
      coefficient (r2 = 0.997, P < 0.01). Therefore, these results indicate that the
      surfactin produced from B. subtilis enhances the bioavailability of hydrophobic
      liquids.

PMID- 15714298
TI  - Selective blockade of nicotinic acetylcholine receptors by pimobendan, a drug for
      the treatment of heart failure: reduction of catecholamine secretion and
      synthesis in adrenal medullary cells.
AB  - Pimobendan, a Ca(2+) sensitizer, is used clinically in the treatment of chronic
      heart failure. Although chronic heart failure is associated with activation of
      the sympathetic nervous system, it remains unknown whether pimobendan affects the
      function of sympathetic neurons and the adrenal medulla. Here, we report the
      inhibitory effects of pimobendan on catecholamine secretion and synthesis in
      cultured bovine adrenal medullary cells. Pimobendan decreased the catecholamine
      secretion (IC(50)=29.5 microM) elicited by carbachol, an agonist at nicotinic
      acetylcholine receptors, but not that elicited by veratridine, an activator of
      voltage-dependent Na(+) channels, or by high K(+), an activator of voltage
      dependent Ca(2+) channels. Pimobendan also inhibited carbachol-induced influx of
      (22)Na(+) (IC(50)=25.9 microM) and (45)Ca(2+) (IC(50)=26.0 microM), but not
      veratridine-induced (22)Na(+) influx or high K(+)-induced (45)Ca(2+) influx. The
      reduction of catecholamine secretion caused by pimobendan was not overcome by
      increasing the concentration of carbachol. UD-CG 212, an active metabolite of
      pimobendan, lowered carbachol-induced catecholamine secretion with a
      concentration/inhibition curve similar to that of pimobendan. In experiments in
      situ, pimobendan suppressed both basal and carbachol-stimulated (14)C
      catecholamine synthesis (IC(50)=5.3 and 4.9 microM) from [(14)C] tyrosine [but
      not from L: -3, 4-dihydroxyphenyl [3-(14)C] alanine ([(14)C]DOPA)], as well as
      tyrosine hydroxylase activity (IC(50)=3.8 and 4.3 microM). These findings suggest
      that pimobendan inhibits carbachol-induced catecholamines secretion and synthesis
      through suppression of nicotinic acetylcholine receptors.

PMID- 15714299
TI  - Time-dependent uptake, distribution and biotransformation of chromium(VI) in
      individual and bulk human lung cells: application of synchrotron radiation
      techniques.
AB  - Chromium(VI) is a human carcinogen, primarily affecting the respiratory tract
      probably via active transport into cells, followed by the reduction to Cr(III)
      with the formation of DNA-damaging intermediates. Distribution of Cr and
      endogenous elements within A549 human lung adenocarcinoma epithelial cells,
      following treatment with Cr(VI) (100 microM, 20 min or 4 h) were studied by
      synchrotron-radiation-induced X-ray emission (SRIXE) of single freeze-dried
      cells. After the 20-min treatment, Cr was confined to a small area of the
      cytoplasm and strongly co-localized with S, Cl, K, and Ca. After the 4-h
      treatment, Cr was distributed throughout the cell, with higher concentrations in
      the nucleus and the cytoplasmic membrane. This time-dependence corresponded to
      approximately 100% or 0% clonogenic survival of the cells following the 20-min or
      4-h treatments, respectively, and could potentially be explained by a new
      cellular protective mechanism. Such processes may also be important in reducing
      the potential hazards of Cr(III) dietary supplements, for which there is emerging
      evidence that they exert their anti-diabetic effects via biological oxidation to
      Cr(VI). The predominance of Cr(III) was confirmed by micro-XANES spectroscopy of
      intracellular Cr hotspots. X-ray absorption spectroscopy (XANES and EXAFS, using
      freeze-dried cells after the 0-4-h treatments) was used to gain insight into the
      chemical structures of Cr(III) complexes formed during the intracellular
      reduction of Cr(VI). The polynuclear nature of such complexes (probably with a
      combination of carboxylato and hydroxo bridging groups and O-donor atoms of small
      peptides or proteins) was established by XAFS data analyses.

PMID- 15714300
TI  - Determination of dopamine in synthetic cerebrospinal fluid by SWV with a graphite
      polyurethane composite electrode.
AB  - This work describes an electroanalytical investigation of dopamine using cyclic
      voltammetry (CV) and the graphite-polyurethane composite electrode (GPU). In CV
      studies, well-defined redox peaks characterize the oxidation process at the GPU
      electrode, which is indicative of electrocatalytic effects associated with active
      sites on the GPU electrode surface. A new analytical methodology was developed
      using the GPU electrode and square wave voltammetry (SWV) in BR buffer solution
      (0.1 mol L(-1); pH 7.4). Analytical curves were constructed under optimized
      conditions (f=60s(-1), DeltaE(a)=50 mV, DeltaE(I)=2 mV) and detection and
      quantification limits of 6.4x10(-8) mol L(-1) (12.1 microg L(-1)) and 5.2x10(-6)
      mol L(-1) (0.9 mg L(-1)), respectively, were achieved. The precision of the
      method was checked by performing ten successive measurements for a 9.9x10(-6) mol
      L(-1) dopamine solution. For intra-assay and inter-assay precisions, the relative
      standard deviations were 1.9 and 2.3%, respectively. In order to evaluate the
      developed methodology, the determination of dopamine was performed with good
      sensitivity and selectivity, without the interference of ascorbic acid in
      synthetic cerebrospinal fluid, which indicates that the new methodology enables
      reliable analysis of dopamine.

PMID- 15714301
TI  - Analysis of cyanobacterial pigments and proteins by electrophoretic and
      chromatographic methods.
AB  - Cyanobacteria are a diverse and ubiquitous group of prokaryotes with several
      unifying features. Amongst these is the macromolecular structure known as the
      phycobilisome, which is composed of water-soluble phycobiliproteins covalently
      bound by linker peptides or proteins in a configuration designed to optimize
      energy transfer to the photosynthetic reaction center of the organism.
      Phycobiliproteins are highly fluorescent by virtue of their covalently bound,
      linear tetrapyrrole chromophores known as bilins. Analysis of these prosthetic
      pigments, along with other non-water soluble pigments, such as the chlorophylls
      and carotenoids, can provide insight into microbial diversity. The effects of
      environmental growth conditions and stresses can also be probed by measuring
      pigment and protein concentrations. This review will focus, therefore, on
      applications of various chromatographic and electrophoretic methods for the
      analysis of cyanobacterial pigment and protein constituents. Although the
      greatest emphasis will be placed on the measurement of bilins and
      phycobiliproteins, this review will also consider other pigments and proteins
      important to cyanobacterial growth and survival, such as chlorophyll a,
      carotenoids, ectoenzymes, linker and membrane proteins, and extracellular
      proteins.

PMID- 15714302
TI  - Verification of statistical-overlap theory in micellar electrokinetic
      chromatography.
AB  - The limited peak capacity of neutral compounds in micellar electrokinetic
      chromatography (MEKC) causes peak overlap in a simple 38-compound sample that is
      predicted by statistical-overlap theory (SOT). The low-concentration sample was
      prepared in-house from several compound classes to span the entire migration-time
      range and was resolved partially in a pH=7 phosphate buffer containing 50 mM
      sodium dodecyl sulfate. Peaks, singlets, doublets, and other multiplets were
      identified on the basis of known migration times and were counted at 13 voltages
      spanning 4 - 26 kV. These numbers agreed well with predictions of a simple SOT
      based on the assumption of an inhomogeneous Poisson distribution of migration
      times. Because the dispersion theory of MEKC is simple, the standard deviations
      of single-component peaks were modeled theoretically. As part of a new way to
      implement SOT, probability distributions of the numbers of peaks, singlets, and
      so on, were computed by Monte Carlo simulation. These distributions contain all
      theoretical information on peak multiplicity predictable by SOT and were used to
      evaluate the agreement between experiment and theory. The peak capacity of MEKC
      was calculated numerically and substituted into the simplest equations in SOT,
      affirming that peak overlap arises from limited peak capacity.

PMID- 15714303
TI  - Interlocking nail for femoral shaft fractures: is dynamization always necessary?
AB  - A series of 179 closed femoral fractures treated by static interlocking nailing
      (Grosse-Kempf nail) was reviewed to evaluate the effect of dynamization on the
      time to bony union. In 75 patients, dynamization was performed whereas in 104 the
      implant was left static. Union occurred in 178 patients. We observed one
      infection. Time to union was significantly shorter in the static group (103 days)
      compared to the dynamized group (126 days).

PMID- 15714304
TI  - Humeral shaft fractures treated by dynamic compression plates, Ender nails and
      interlocking nails.
AB  - Between January 1991 and December 2002, we treated 92 acute, displaced, closed
      humeral shaft fractures (AO classification type A). We used three fixation
      methods: dynamic compression plates (DCP) in 36 patients, Ender nails (EN) in 32
      patients and interlocking nails (ILN) in 24 patients. The patients were followed
      for a minimum of 24 months. At one year, all fractures except two (one DCP/one
      ILN) had united. Patients treated with EN had shorter mean operation time, 51 (35
      110) min; less mean blood loss, 70 (30-170) ml and shorter mean hospital stay,
      5.8 (3-12) days. There were three iatrogenic radial nerve palsies: two in the DCP
      group and one in the ILN group. There was one wound infection. There were three
      cases with impingement of the shoulder but range of motion was restored after
      nail removal. For patients with multiple trauma or high operative risk, EN
      fixation served as a safer and faster procedure. ILN fixation offered a stable
      fixation via a smaller incision but more fracture comminution might happen.

PMID- 15714305
TI  - Conservative treatment of fractures of the thoracolumbar spine.
AB  - We reviewed 48 patients with thoracolumbar fractures treated conservatively
      between 1988 and 1999. The average follow-up was 77.5 (31-137) months and average
      patient age (23 women, 25 men) was 46 (18-76) years. Twenty-nine patients
      suffered a fall from a height and 13 patients were injured in traffic accidents.
      Thirty-two patients had compression-type fractures and 16 burst-type fractures.
      There were no neurological deficits. Twenty-nine patients were treated by
      orthosis, 13 by body cast and six by bed rest. In addition to pain and functional
      scoring, we measured a number of radiographic parameters at the time of admission
      and at latest follow-up and compared the values. In patients with compression
      fractures there were significant changes in scoliosis angle and wedging index
      (p<0.05). The mean pain score was 1.66 and mean functional score 1.03. In
      patients with burst fractures, vertebral index, wedging index and height loss
      increased after treatment (p<0.05). The mean pain score was 1.26 and functional
      score 0.93. Compression fractures with kyphosis angle <30 degrees are supposed to
      be stable and can be treated conservatively. If the kyphosis angle is more than
      30 degrees, magnetic resonance imaging (MRI) should be performed, and if the
      posterior ligamentous complex is damaged, surgery should be considered. In burst
      fractures, MRI should always be performed and conservative treatment should only
      be considered if there is no neurological deficit and the ligaments are intact.

PMID- 15714306
TI  - T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N
      terminal proline at p-1.
AB  - Recent research has implicated a large number of gluten-derived peptides in the
      pathogenesis of celiac disease, a preponderantly HLA-DQ2-associated disorder.
      Current evidence indicates that the core of some of those peptides is ten amino
      acids long, while HLA class II normally accommodates nine amino acids in the
      binding groove. We have now investigated this in detail, using gluten-specific T
      cell clones, HLA-DQ2-specific peptide-binding assays and molecular modelling. T
      cell recognition of both a gamma-gliadin peptide and a low-molecular-weight
      glutenin peptide was found to be strictly dependent on a ten-amino acids-long
      peptide. Subsequent peptide-binding studies indicated that the glutenin peptide
      bound in a conventional p1/p9 register, with an additional proline at p-1.
      Testing of substitution analogues demonstrated that the nature of the amino acid
      at p-1 strongly influenced T-cell recognition of the peptide. Moreover, molecular
      modelling confirmed that the glutenin peptide binds in a p1/p9 register, and that
      the proline at p-1 points upward towards the T-cell receptor. Database searches
      indicate that a large number of potential T-cell stimulatory gluten peptides with
      an additional proline at relative position p-1 exist, suggesting that the
      recognition of other gluten peptides may depend on this proline as well. This
      knowledge may be of importance for the identification of additional T-cell
      stimulatory gluten peptides and the design of a peptide-based, tolerance-inducing
      therapy.

PMID- 15714307
TI  - Analysis of the sequence variations in the Mhc DRB1-like gene of the endangered
      Humboldt penguin (Spheniscus humboldti).
AB  - The Major Histocompatibility Complex (Mhc) genomic region of many vertebrates is
      known to contain at least one highly polymorphic class II gene that is homologous
      in sequence to one or other of the human Mhc DRB1 class II genes. The diversity
      of the avian Mhc class II gene sequences have been extensively studied in
      chickens, quails, and some songbirds, but have been largely ignored in the
      oceanic birds, including the flightless penguins. We have previously reported
      that several penguin species have a high degree of polymorphism on exon 2 of the
      Mhc class II DRB1-like gene. In this study, we present for the first time the
      complete nucleotide sequences of exon 2, intron 2, and exon 3 of the DRB1-like
      gene of 20 Humboldt penguins, a species that is presently vulnerable to the
      dangers of extinction. The Humboldt DRB1-like nucleotide and amino acid sequences
      reveal at least eight unique alleles. Phylogenetic analysis of all the available
      avian DRB-like sequences showed that, of five penguin species and nine other bird
      species, the sequences of the Humboldt penguins grouped most closely to the
      Little penguin and the mallard, respectively. The present analysis confirms that
      the sequence variations of the Mhc class II gene, DRB1, are useful for
      discriminating among individuals within the same penguin population as well those
      within different penguin population groups and species.

PMID- 15714308
TI  - A method for surveying and classifying Leuconostoc spp. glucansucrases according
      to strain-dependent acceptor product patterns.
AB  - A number of Leuconostoc spp. strains were screened for their ability to produce
      glucansucrases and carry out acceptor reactions with maltose. Acceptor products
      were analyzed by thin-layer chromatography (TLC) and it was discovered that they
      could be grouped into four distinct categories based on oligosaccharide product
      patterns. These patterns corresponded with structural features of the dextrans
      each strain is reported to produce. Strains that produced a typical dextran
      characterized by a predominantly linear alpha(1-->6)-linked D: -glucan chain with
      a low to moderate degree of branching-produced a homologous series of
      isomaltooligosaccharides via acceptor reactions. Strains that produced dextrans
      with moderate to high levels of alpha(1-->2) branch points, exemplified by NRRL B
      1299, synthesized the same isomaltodextrins as well as another series of
      oligosaccharides migrating slightly faster in our TLC system. Strains that
      produced dextrans with higher levels of alpha(1-->3)-branches, such as NRRL B
      742, synthesized isomaltodextrins plus a series of oligosaccharides that migrated
      slightly more slowly on TLC. And finally, strains known to produce
      alternansucrase produced isomaltodextrins plus oligoalternans. Within a given
      type, variability exists in the relative proportions of each product. The data
      presented here may be useful in selecting strains for the production of specific
      types of oligosaccharides, for example as prebiotics.

PMID- 15714309
TI  - Bilateral calcifications in the basal ganglia, and frontal and parietal lobes of
      a patient with coeliac disease.
AB  - Previous authors have described a specific syndrome of coeliac disease, bilateral
      cerebral calcifications and epileptic seizures. We report a 4-year-old boy with
      coeliac disease who had bilateral calcifications in the basal ganglia and frontal
      and parietal lobes, but did not exhibit epileptic seizures.

PMID- 15714310
TI  - Pulmonary capillary haemangiomatosis in a premature infant.
AB  - Pulmonary capillary haemangiomatosis (PCH) is a rare disorder characterized by
      widespread capillary proliferation in the lung, infiltrating the interstitium and
      the alveolar walls. We present the HRCT features of PCH in a surviving ex
      premature infant. To our knowledge, this is a unique case of the radiological
      features of PCH in a young living infant.

PMID- 15714311
TI  - 24-hour ambulatory blood pressure monitoring in children with familial
      dysautonomia.
AB  - BACKGROUND: Familial dysautonomia (Riley Day syndrome) is a genetic disease. The
      present study of 24-hour ambulatory blood pressure monitoring in children with
      familial dysautonomia was carried out to investigate the pattern of blood
      pressure in this syndrome. OBJECTIVE: To the best of our knowledge, this is the
      only description of patients with 24-hour blood pressure monitoring. STUDY
      DESIGN: Vasomotor instability reflected in extreme hypertension and hypotension
      was recorded by 24-hour ambulatory blood pressure monitoring in three patients
      with familial dysautonomia: a 16-year old girl, a 14-year old boy and a 3-year
      old boy. Recordings were taken on a routine school day in the first two patients
      and during hospitalization in the third. RESULTS: Patients 1 and 2 displayed
      circadian rhythm but with significantly higher than normal blood pressure and
      heart rate. Patient 3 exhibited these fluctuations to a lesser degree. Postural
      hypotension without compensatory tachycardia was frequently seen in all three
      patients. Unusual variability in blood pressure was recorded during routine
      activities in patients 1 and 2 and during an acute attack in patient 3.
      CONCLUSIONS: Close monitoring of antihypertensive therapy should be considered in
      familial dysautonomia patients in whom blood pressure reaches excessive levels.

PMID- 15714312
TI  - Precursor B-cell lymphoblastic leukemia as a cause of a bilateral nephromegaly.
AB  - Nephromegaly and non-oliguric acute renal failure is an unusual manifestation of
      lymphoblastic infiltration of the kidneys. We report the clinical history of a
      female child where a precursor B-cell lymphoblastic proliferation was diagnosed
      at the age of 21 months by a surgical renal biopsy for an unexplained bilateral
      nephromegaly. Lymphoblastic infiltration should be suspected in any patient
      presenting with unexplained renal failure and enlarged kidneys. The importance of
      renal biopsy to identify the etiology of renal failure and nephromegaly is
      emphasized.

PMID- 15714313
TI  - Glycosaminoglycan excretion in children with nephrotic syndrome.
AB  - Although most childhood nephrotic syndromes respond to steroid treatment, steroid
      resistant nephrotic syndrome (SRNS) is also common and is particularly difficult
      to treat. This study investigated the role of glycosaminoglycans (GAG) in the
      pathogenesis and clinical course of nephrotic syndrome in children. Thirty-four
      children (21 males and 13 females, mean age 3.7+/-1.6 years) with steroid
      sensitive nephrotic syndrome and 20 children with steroid-resistant nephrotic
      syndrome (12 males and 8 females, mean age 10.9+/-3.8 years; of the twenty, four
      had primary SRNS (FSGS) and the others had secondary SRNS) were included the
      study. Mean urine levels of GAG relative to creatinine (U(GAG)/U(Cr)) in patients
      with SRNS (n=20, 113.01+/-78.46 mg g(-1) Cr) and in patients experiencing the
      nephrotic period of steroid-sensitive nephrotic syndrome (n=34, 132.15+/-101.55
      mg g(-1) Cr) were both significantly higher than mean U(GAG)/U(Cr) for control
      subjects (n=30, 51.83+/-47.66 mg g(-1) Cr) (P<0.01 for both). Patients excreted
      significantly more GAG during the nephrotic period of steroid-sensitive nephrotic
      syndrome than during remission (132.15+/-101.55 vs 39.11+/-42.73 mg g(-1) Cr,
      respectively; P<0.01). There was, however, no significant difference between
      U(GAG)/U(Cr) for patients with steroid-resistant nephrotic syndrome and
      U(GAG)/U(Cr) in the nephrotic period of steroid-sensitive nephrotic syndrome.
      Urine GAG excretion correlated significantly with the severity of proteinuria.
      The results suggest that GAG play a significant role in the pathogenesis of
      nephrotic syndrome but that GAG excretion is not a marker for response to steroid
      treatment in pediatric patients with this condition.

PMID- 15714314
TI  - Extra corporeal membrane oxygenation and plasmapheresis for pulmonary hemorrhage
      in microscopic polyangiitis.
AB  - Early initiation of extracorporeal membrane oxygenation to treat acute hypoxemic
      respiratory failure secondary to massive pulmonary hemorrhage in microscopic
      polyangiitis in children can be life-saving while awaiting control of the
      autoimmune disease process by plasmapheresis and immunosuppression.

PMID- 15714315
TI  - Central, but not peripheral application of motilin increases c-Fos expression in
      hypothalamic nuclei in the rat brain.
AB  - Previous immunocytochemical studies have shown the presence of motilin
      immunoreactive neurons in specific brain areas of rats and autoradiographic
      studies in rabbits demonstrated motilin-binding sites in the central nervous
      system as well. Therefore, the aim of this study was to determine the anatomical
      localisation and neurochemical features of neurons activated by central
      administration of motilin (Mo) in rats. One week after cannulation, an
      intracerebroventricular injection of Mo (ICV, 3 microg/6 mul 0.9% saline) was
      given. For comparative purposes, a group of animals received an intravenous
      injection of motilin (IV, 9 microg/300 mul 0.9% saline) or an equal volume of
      saline. Neuronal excitation was assessed by c-Fos immunocytochemistry and
      combined with immunostaining for neurotransmitter markers. In contrast to the IV
      motilin-treated animals, the ICV motilin-treated animals displayed a significant
      increase in c-Fos expression in the supraoptic nuclei (SO) and paraventricular
      nuclei of the hypothalamus (PVH). At the level of the dorsomedial, ventromedial
      and lateral hypothalamic nuclei, ICV administration of motilin did not induce
      changes in c-Fos expression. In addition, the cerebellum did not show c-Fos
      expression after ICV motilin administration either. These findings might suggest
      distinct pathways and actions of centrally released and systemic motilin, but,
      particularly in rodents, do not rule out the possibility that the effects seen in
      the SO and PVH after ICV application are aspecific in nature. At present, we
      cannot exclude the fact that the results observed with motilin in rodents are due
      to cross-interaction with other related (e.g. ghrelin) or not yet identified
      receptors.

PMID- 15714316
TI  - Congenital disorder of glycosylation type Ia: a clinicopathological report of a
      newborn infant with cerebellar pathology.
AB  - Congenital disorders of glycosylation (CDG) represent a newly delineated group of
      inherited multisystem disorders characterized by defective glycoprotein
      biosynthesis. In the present study we report and discuss the clinical and
      neuropathological findings in a newborn with CDG type Ia (CDG-Ia). The patient
      presented mild dysmorphic facial features, inverted nipples, progressive
      generalized edema, hypertrophic cardiomyopathy, hepatosplenomegaly, muscular
      hypotonia and had severe hypoalbuminemia. Deficiency of phosphomannomutase (PMM)
      2 activity was detected. Molecular analysis showed V231M/T237R mutations of the
      PMM2 gene. Muscular biopsy, disclosed myopathic alterations with myofibrillar
      disarray by electron microscopy. The patient died at 1 month of age of
      circulatory and respiratory failure. Autopsy showed liver fibrosis and renal
      abnormalities. Neuropathological abnormalities were mainly confined to the
      cerebellum. Histological and immunocytochemical examination of cerebellar tissue
      showed partial atrophy of cerebellar folia with severe loss of Purkinje cells,
      granular cell depletion and various morphological changes in the remaining
      Purkinje cells and their dendritic arborization. Autopsy findings confirm the
      complexity of the CDG-Ia syndrome, and indicate that CDG-Ia is a distinct disease
      entity, which can be differentiated from other neurological disorders and other
      types of CDG, not only clinically, but also based on unique pathological
      findings. The data proved useful in determining the underlying disease process
      associated with a defective N-glycosylation pathway.

PMID- 15714317
TI  - Alteration of the embryo transcriptome of hexaploid winter wheat (Triticum
      aestivum cv. Mercia) during maturation and germination.
AB  - Grain dormancy and germination are areas of biology that are of considerable
      interest to the cereal community. We have used a 9,155-feature wheat unigene cDNA
      microarray resource to investigate changes in the wheat embryo transcriptome
      during late grain development and maturation and during the first 48 h of
      postimbibition germination. In the embryo 392 mRNAs accumulated by twofold or
      greater over the time course from 21 days postanthesis (dpa) to 40 dpa and on
      through 1 and 2 days postgermination. These included mRNAs encoding proteins
      involved in amino acid biosynthesis and metabolism, cell division and subsequent
      cell development, signal transduction, lipid metabolism, energy production,
      protein turnover, respiration, initiation of transcription, initiation of
      translation and ribosomal composition. A number of mRNAs encoding proteins of
      unknown function also accumulated over the time course. Conversely 163 sequences
      showed decreases of twofold or greater over the time course. A small number of
      mRNAs also showed rapid accumulation specifically during the first 48 h of
      germination. We also examined alterations in the accumulation of transcripts
      encoding proteins involved in abscisic acid signalling. Thus, we describe changes
      in the level of transcripts encoding wheat Viviparous 1 (Vp1) and other
      interacting proteins. Interestingly, the transcript encoding wheat Viviparous
      interacting protein 1 showed a pattern of accumulation that correlates inversely
      with germination. Our data suggests that the majority of the transcripts required
      for germination accumulate in the embryo prior to germination and we discuss the
      implications of these findings with regard to manipulation of germination in
      wheat.

PMID- 15714319
TI  - In vitro recombination cloning of entire cDNA libraries in Arabidopsis thaliana
      and its application to the yeast two-hybrid system.
AB  - In the postgenomic era many experiments rely on the availability of transcript
      sequence for cloning. As these clones usually originate from cDNA libraries, the
      quality of these libraries is crucial. If a good library is generated it is
      desirable to use a versatile cloning system suitable for many different kinds of
      applications. The cloning systems based on in vitro recombination proves fitting
      for this task. However, the use of this method for shuttling entire cDNA
      libraries between different vectors has not yet been studied in great detail.
      Here we describe the construction of four cDNA libraries from different tissues
      of Arabidopsis thaliana, the shuttling of the libraries into expression vectors,
      and evaluation of this method as well as its suitability for downstream
      applications. Libraries were constructed from seedlings, hormone treated
      seedlings, flowers, developing seeds and primary leaves in the "entry vector" of
      the Gateway cloning system. After initial characterization of the libraries, they
      were shuttled into an expression vector (a yeast two-hybrid prey vector). To
      monitor for a size bias generally assumed to be inherent to in vitro
      recombination methods, the libraries were characterized before and after the
      transfer into the expression vector. However no significant difference could be
      detected. The functionality of the in vitro recombination system for the
      shuttling of entire libraries was then further tested by protein-protein
      interaction screens. The results of the library characterization and of the yeast
      two-hybrid screens and their implications for large-scale proteomic approaches
      are discussed.

PMID- 15714318
TI  - A comparative analysis of transcript abundance using SAGE and Affymetrix arrays.
AB  - A number of methods are currently used for gene expression profiling. They differ
      in scale, economy and sensitivity. We present the results of a direct comparison
      between serial analysis of gene expression (SAGE) and the Barley1 Affymetrix
      GeneChip. Both technology platforms were used to obtain quantitative measurements
      of transcript abundance using identical RNA samples and assessed for their
      ability to quantify differential gene expression. For SAGE, a total of 82,122
      tags were generated from two independent libraries representing whole developing
      barley caryopsis and dissected embryos. The Barley1 GeneChip contains 22,791
      probe sets. Results obtained from both methods are generally comparable,
      indicating that both will lead to similar conclusions regarding transcript levels
      and differential gene expression. However, excluding singletons, 24.4% of the
      unique SAGE tags had no corresponding probe set on the Barley1 array indicating
      that a broader snapshot of gene expression was obtained by SAGE. Discrepancies
      were observed for a number of "genes" and these are discussed.

PMID- 15714320
TI  - Microarray analysis of gene expression in germinating barley embryos (Hordeum
      vulgare L.).
AB  - A cDNA library containing approximately 5,000 clones from germinating barley
      embryos was constructed and used to examine the variation in gene expression
      patterns during the first 4 days postimbibition. The expression profiles of
      embryos (including scutellum) from 4 to 96 h postimbibition were compared to a
      reference profile from 24 h postimbibition using microarray analysis. A subset of
      clones exhibiting tenfold or greater differential expression patterns was
      sequenced to elucidate function. All of the sequenced clones could be identified
      to at least EST level with 64% exhibiting homology to published protein
      sequences. Almost 95% of the library exhibited similar expression levels at the 4
      h time point as at the 24 h reference point. From 24 to 96 h, however,
      considerable fluctuations in gene expression occurred. The observed patterns of
      gene expression for the classified genes are consistent with the expected genetic
      changes required to prepare an embryo for germinative development. A replicate
      set of clones for the 23-kDa jasmonate-induced protein was identified. The
      current data not only provides conclusive evidence for the expression patterns of
      this abundant stress-response protein in germinating embryos, but also serves to
      validate previous research into JIP-23 isoforms, function and the relationship
      between timing of mRNA upregulation and protein abundance.

PMID- 15714321
TI  - Hybrid lethality of cultured cells of an interspecific F1 hybrid of Nicotiana
      gossei Domin and N. tabacum L.
AB  - Cultured cells were established from the hypocotyl of F(1) hybrid seedlings of
      Nicotiana gossei Domin and N. tabacum L. The cultured cells started to die at 26
      degrees C, but not at 37 degrees C, which is similar to what occurred in cells of
      the original hybrid plants. An increase in the number of cells without
      cytoplasmic strands and acidification of the cytoplasm followed by decomposition
      of the mitochondria and chloroplasts indicated that vacuolar collapse plays a
      central role in the execution of cell death. Oxygen but not light was required
      for cell death. Cellular levels of the superoxide anion and hydrogen peroxide
      temporarily increased during the early phase at 26 degrees C, while no such
      oxidative burst was observed at 37 degrees C. The reactive oxygen intermediates
      are potentially involved in the death of the hybrid cells.

PMID- 15714322
TI  - Matrix attachment region from the chicken lysozyme locus reduces variability in
      transgene expression and confers copy number-dependence in transgenic rice
      plants.
AB  - Matrix-attachment regions (MARs) may function as domain boundaries and partition
      chromosomes into independently regulated units. In this study, BP-MAR, a 1.3-kb
      upstream fragment of the 5'MAR flanking the chicken lysozyme locus, was tested
      for its effects on integration and expression of transgenes in transgenic rice
      plants. Using the Agrobacterium-mediated method, we transformed rice with nine
      different constructs containing seven and six different promoters and coding
      sequences, respectively. Genomic Southern blot analyses of 357 independent
      transgenic lines revealed that in the presence of BP-MAR, 57% of the lines
      contained a single copy of the transgene, whereas in its absence, only 20% of the
      lines contained a single copy of the transgene. RNA gel-blot and immunoblot
      experiments demonstrated that in the presence of BP-MAR, transgene expression
      levels were similar among different lines. These data were in direct contrast to
      those derived from transgenes expressed in the absence of BP-MAR, which varied
      markedly with the chromosomal integration site . Thus, it can be concluded that
      BP-MAR significantly reduces the variability in transgene expression between
      independent transformants. Moreover, the presence of BP-MAR appears to confer a
      copy number-dependent increase in transgene expression, although it does not
      increase expression levels of individual transgenes. These data contrast with
      results previously obtained with various MARs that increased expression levels of
      transgene significantly. Therefore, we conclude that the incorporation of BP-MAR
      sequences into the design of transformation vectors can minimize position effects
      and regulate transgene expression in a copy number-dependent way.

PMID- 15714323
TI  - Withdrawal following sufentanil/propofol and sufentanil/midazolam. Sedation in
      surgical ICU patients: correlation with central nervous parameters and endogenous
      opioids.
AB  - PURPOSE: Patients in the ICU after long-term administration of an opioid/hypnotic
      often develop delirium. To assess the nature of this phenomenon, patients in a
      surgical ICU following ventilatory support and sedation with an
      opioid/hypnotic/sedative were studied. METHODOLOGY: Following
      sufentanil/midazolam (group 1; n =14) or sufentanil/propofol (group 2; n =15)
      sedation, patients were evaluated for changes in mean arterial blood pressure and
      heart rate, the activity of the central nervous system (sensory evoked
      potentials, spectral edge frequency of EEG), and the endogenous opioids plasma
      concentrations (beta-endorphin, met-enkephalin). Data obtained were correlated
      with the individual intensities of withdrawal symptoms 6-, 12-, and 24 h
      following sedation. RESULTS: Following a mean duration of ventilation of 7.7 days
      (+/-3.6 SD) in groups 1 and 3.5 (+/-1.7 SD) in group 2, withdrawal intensities
      peaked within the 6th hour after cessation. Plasma beta-endorphin and met
      enkephalin levels were low during sedation, and only the sufentanil/midazolam
      group demonstrated a postinhibitory overshoot. Withdrawal symptom intensities
      demonstrated an inverse correlation with beta-endorphin and met-enkephalin
      levels, a direct linear correlation with amplitude height of the evoked
      potential, and blood pressure and heart rate changes. Withdrawal intensities did
      not correlate with EEG power spectral edge frequency. CONCLUSION: The
      endorphinergic system is suppressed when a potent exogenous opioid like
      sufentanil is given over a long period of time. Following sedation, abstinence
      symptoms seem to be related to postinhibitory increased endorphin synthesis. This
      is mostly seen in the combination of sufentanil/midazolam. In addition, an
      increase in the amplitude of the sensory-evoked potential suggests a
      postinhibitory excitatory state within the nociceptive system.

PMID- 15714325
TI  - A mutation, tl2, in pea (Pisum sativum L.) affects leaf development only in the
      heterozygous state.
AB  - After gamma irradiation of pea seeds, a mutation designated as tendril-less2
      (tl2) was induced. In the heterozygous state, it transforms tendrils into very
      narrow leaflets that resemble the heterozygote phenotype of the classic tl
      mutation. The tendrils of the double heterozygote tl2/+, tl/+ are converted into
      oval leaflets. Unlike tl, the novel mutation in the homozygous state does not
      affect tendrils. The leaf phenotype of homozygotes tl2/tl2 and Tl2/Tl2 do not
      differ in the tl/+ background. However, the anthocyanin pigmentation is strongly
      suppressed in petals of tl2/tl2 plants. Some hypotheses to explain the unusual
      phenotypic manifestation of tl2 are suggested.

PMID- 15714324
TI  - Sedation in the critically ill ventilated patient: possible role of enteral
      drugs.
AB  - OBJECTIVE: Sedation by the enteral route is unusual in intensive medicine. We
      analysed the feasibility/efficacy of long-term enteral sedation in ventilated
      critically ill patients. DESIGN: Prospective interventional cohort study.
      SETTING: General ICU. PATIENTS AND PARTICIPANTS: Forty-two patients needing
      ventilation and sedation for at least 4 days. INTERVENTIONS: At admission,
      sedation was induced with propofol or midazolam. Enteral hydroxyzine (+/- enteral
      lorazepam) was added in all patients within the second day. Intravenous drugs
      were gradually withdrawn, trying to maintain only enteral sedation after the
      initial 48 h. Analgesia was provided with continuous IV fentanyl. MEASUREMENTS
      AND RESULTS: Sedation level was assessed evaluating, on a daily basis, patients'
      compliance to the invasive care and comparing observed vs planned Ramsay scores
      three times a day. Excluding the first 2 days of patient-stabilisation and fast
      titration of sedation level, 577 days with ventilatory support were analysed. In
      460 days (79.7%) total enteral sedation was given. This percentage rose to 94.2%
      when the requested Ramsay was 2 (347 days). Daily sedation was judged as adequate
      in 82.8% of days of total enteral sedation. Thirty-one patients had total enteral
      as the exclusive route of sedation. CONCLUSIONS: After 24-48 h, enteral sedation
      may replace, totally/in part, IV sedation in ventilated patients. Total enteral
      sedation easily fits the target when a Ramsay score 2 is planned. When a deeper
      sedation is needed, a mixed regimen is effective and lowers IV drug dosages. No
      side effects were reported.

PMID- 15714326
TI  - A reconsideration of the domestication geography of tetraploid wheats.
AB  - The domestication of tetraploid wheats started from their wild progenitor
      Triticum dicoccoides. In this paper, the geographical distribution of this
      progenitor is revised to include more sampling locations. The paper is based on a
      collection of wild and domesticated lines (226 accessions in total) analyzed by
      AFLP at 169 polymorphic loci. The collection includes the 69 wild lines
      considered by Mori et al. (2003) in their study on chloroplast DNA haplotypes of
      T. dicoccoides. The goal of the experiment was to reconsider which location
      thought to have generated the domesticated germplasm has the highest chance of
      being the actual site from which wild progenitors were sampled during
      domestication. Phylogenetic analysis of the nuclear AFLP databases indicates that
      two different genetic taxa of T. dicoccoides exist, the western one, colonizing
      Israel, Syria, Lebanon and Jordan, and the central-eastern one, which has been
      frequently sampled in Turkey and rarely in Iran and Iraq. It is the central
      eastern race that played the role of the progenitor of the domesticated
      germplasm. This is supported by the cumulative results of the AFLP data from the
      collections of Ozkan et al. (2002) and of Mori et al. (2003), which indicate that
      the Turkish Karacadag population, intermixed with some Iraq-Iran lines, has a
      tree topology consistent with that of the progenitor of domesticated genotypes.
      The Turkish Kartal population belongs genetically to the central-eastern T.
      dicoccoides race but at the nuclear DNA level is less related to the domesticated
      gene pool. A general agreement between published work on tetraploid wheat
      domestication emerges from these results. A disagreement is nevertheless evident
      at the local geographical scale; the chloroplast DNA data indicate the Kartal
      mountains while AFLP fingerprinting points to the Karacadag Range as the putative
      site of tetraploid wheat domestication.

PMID- 15714327
TI  - Molecular changes in the maize composite EPS12 during selection for resistance to
      pink stem borer.
AB  - The pink stem borer (Sesamia nonagrioides Lefevbre) is the most important pest of
      maize (Zea mays L.) throughout the Mediterranean area. The maize composite EPS12
      has been chosen as the base population for a breeding program based on its
      resistance to pink stem borer, with the main selection criterion being resistance
      to stem tunneling. Yield was taken as a secondary selection criterion to avoid
      any unwanted negatively correlated response on this character. The aims of
      investigation were: (1) to monitor the effects of selection for resistance to
      pink stem borer on allele frequency at 70 simple sequence repeat (SSR) markers
      and their impact on the genetic structure of EPS12 and (2) to identify loci at
      which allelic frequencies changed significantly due to directional selection.
      Genetic diversity was reduced during the selection process (as expected since
      random genetic drift as well as selection could reduce genetic variability), but
      not significantly so. Although the loss of genetic variation was generally
      consistent with that expected in a model in which random genetic drift acts alone
      on neutral alleles, the changes observed in the frequency of five alleles were
      significantly greater than expected. Further, the linear trend of the departure
      from the random genetic drift model was significant for some allelic versions of
      two SSR markers, umc1329 and phi076; directional selection was therefore acting
      on these loci. The significant effect of directional selection on those markers
      suggests the presence of quantitative trait loci (QTLs) for tunnel length and/or
      for yield under artificial infestation with Sesamia nonagrioides on the long arm
      of chromosome 4.

PMID- 15714328
TI  - Bacterial artificial chromosome-derived molecular markers for early bolting in
      sugar beet.
AB  - Early bolting in sugar beet (Beta vulgaris L.) is controlled by the dominant gene
      B. From an incomplete physical map around the B gene, 18 bacterial artificial
      chromosomes (BACs) were selected for marker development. Three BACs were shotgun
      sequenced, and 61 open reading frames (ORFs) were identified. Together with 104
      BAC ends from 54 BACs, a total number of 55,464 nucleotides were sequenced. Of
      these, 37 BAC ends and 12 ORFs were selected for marker development. Thirty-one
      percent of the sequences were found to be single copy and 24%, low copy. From
      these sequences, 15 markers from ten different BACs were developed. Ten
      polymorphisms were determined by simple agarose gel electrophoresis of either
      restricted or non-restricted PCR products. Another five markers were determined
      by tetra-primer amplification refractory mutation system-PCR. In order to select
      candidate BACs for cloning the gene, genetic linkage between seven markers and
      the bolting gene was calculated using 1,617 plants from an F2 population
      segregating for early bolting. The recombination values ranged between 0.0033 and
      0.0201. In addition, a set of 41 wild and cultivated Beta accessions differing in
      their early bolting character was genotyped with seven markers. A common
      haplotype encompassing two marker loci and the b allele was found in all sugar
      beet varieties, indicating complete linkage disequilibrium between these loci.
      This suggests that the bolting gene is located in close vicinity to these
      markers, and the corresponding BACs can be used for cloning the gene.

PMID- 15714330
TI  - Partial sequences of nitrogen metabolism genes in hexaploid wheat.
AB  - Our objective was to partially sequence genes controlling nitrogen metabolism in
      wheat species in order to find sequence polymorphism that would enable their
      mapping. Primers were designed for nitrate reductase, nitrite reductase,
      glutamate dehydrogenase and glutamate synthase (GOGAT), and gene fragments were
      amplified on Triticum aestivum, T. durum, T. monococcum, T. speltoides and T.
      tauschii. We obtained more than 8 kb of gene sequences, mainly as coding regions
      (60%). Polymorphism was quantified by comparing two-by-two the three genomes of
      the hexaploid cultivar Arche and genomes of diploid wheat species. On average,
      the polymorphism rate was higher for non-coding regions, where it ranged from
      1/60 to 1/23, than for coding regions (range: 1/110-1/40) except when the
      hexaploid D genome was compared to that of T. tauschii (1/800 and 1/816,
      respectively). Genome-specific primers were devised for the ferredoxin-dependent
      (Fd)-GOGAT gene, and they enabled the mapping of this gene on homoeologous
      chromosomes of group 2 using Chinese Spring deletion lines. A single nucleotide
      polymorphism (SNP) detected between the two hexaploid wheat cultivars Arche and
      Recital was used to genetically map Fd-GOGAT on chromosome 2D using a population
      of dihaploid lines. Fd-GOGAT-specific primers were used to estimate the SNP rate
      on a set of 11 hexaploid and nine Durum wheat genotypes leading to the estimate
      of 1 SNP/515 bp. We demonstrate that polymorphism detection enables heterologous,
      homeologous and even paralogous copies to be assigned, even if the elaboration of
      specific primer pairs is time-consuming and expensive because of the sequencing.

PMID- 15714329
TI  - Characterization and mapping of NBS-LRR resistance gene analogs in apricot
      (Prunus armeniaca L.).
AB  - Genomic DNA sequences sharing homology with the NBS-LRR (nucleotide binding site
      leucine-rich repeat) resistance genes were isolated and cloned from apricot
      (Prunus armeniaca L.) using a PCR approach with degenerate primers designed from
      conserved regions of the NBS domain. Restriction digestion and sequence analyses
      of the amplified fragments led to the identification of 43 unique amino acid
      sequences grouped into six families of resistance gene analogs (RGAs). All of the
      RGAs identified belong to the Toll-Interleukin receptor (TIR) group of the plant
      disease resistance genes (R-genes). RGA-specific primers based on non-conserved
      regions of the NBS domain were developed from the consensus sequences of each RGA
      family. These primers were used to develop amplified fragment length polymorphism
      (AFLP)-RGA markers by means of an AFLP-modified procedure where one standard
      primer is substituted by an RGA-specific primer. Using this method, 27
      polymorphic markers, six of which shared homology with the TIR class of the NBS
      LRR R-genes, were obtained from 17 different primer combinations. Of these 27
      markers, 16 mapped in an apricot genetic map previously constructed from the self
      pollination of the cultivar Lito. The development of AFLP-RGA markers may prove
      to be useful for marker-assisted selection and map-based cloning of R-genes in
      apricot.

PMID- 15714331
TI  - Prophylactic application of fluoroquinolones for selective decontamination of the
      gut: friend or foe.

PMID- 15714332
TI  - Fluoroquinolone resistance of Escherichia coli at a cancer center: epidemiologic
      evolution and effects of discontinuing prophylactic fluoroquinolone use in
      neutropenic patients with leukemia.
AB  - The aim of the present study was to investigate the epidemiologic evolution of
      fluoroquinolone resistance of E. coli clinical isolates from patients admitted to
      a hematology-oncology service where fluoroquinolone prophylaxis during
      neutropenia was recommended as the standard of care for many years but was then
      discontinued in a trial conducted in patients with acute leukemia.
      Fluoroquinolones had been shown to decrease the incidence of gram-negative
      bacteremia in cancer patients with neutropenia, yet it was thought that the
      emergence of resistance in Escherichia coli and other gram-negative bacteria may
      have caused a progressive lack of efficacy of fluoroquinolone prophylaxis.
      Epidemiologic surveillance of fluoroquinolone resistance of E. coli clinical
      isolates at our cancer center since 1992 showed a continuing influx of new clones
      not previously observed in the population of cancer patients, an increase in the
      number of cancer patients per year colonized and/or infected by fluoroquinolone
      resistant E. coli (1992-1994, 10-16 patients; 1995-1997, 24-27 patients), and a
      resistance rate of >50% among E. coli bloodstream isolates of hematology-oncology
      patients. A 6-month fluoroquinolone prophylaxis discontinuation intervention
      trial in 1998 suggested that despite increasing resistance among E. coli
      isolates, fluoroquinolone prophylaxis in acute leukemia patients was still
      effective in the prevention of gram-negative bacteremia (incidence rates, 8%
      during the pre-intervention period vs. 20% after discontinuation; p<0.01). The
      resumption of fluoroquinolone prophylaxis in acute leukemia patients thereafter
      decreased the incidence of gram-negative bacteremia to the pre-intervention level
      (9%; p=0.03), while the proportion of in vitro fluoroquinolone resistance in E.
      coli bacteremia isolates again increased (from 15% during the intervention period
      to >50% in the post-intervention period). Relative rates of resistance thus were
      a poor indicator of the potential clinical benefits associated with
      fluoroquinolone prophylaxis in cancer patients.

PMID- 15714333
TI  - Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated
      with airway hyperresponsiveness.
AB  - Airway hyperresponsiveness (AHR) is one of the major clinical symptoms and
      intermediate phenotypes of asthma. A recent genome-wide search for asthma
      quantitative trait loci has revealed a significant linkage signal between a p
      terminal region of chromosome 2 and AHR. Thus, the gene encoding the potassium
      voltage-gated channel delayed-rectifier protein S3 (KCNS3) in this region is
      considered a positional candidate for asthma. We have evaluated a total of 12
      single-nucleotide polymorphisms (SNPs) of the KCNS3 gene in a validation panel of
      48 lymphoblastoid cell line DNA samples of Chinese origin. Three SNPs were found
      to be polymorphic and were tested. Two independent sets (an initial screening set
      and a replication set) of cases and controls from the original linkage study
      sample were collected. In the initial screening set, two SNPs (rs1031771 and
      rs1031772) showed suggestive association and were further confirmed by the
      replication set. In combined single-SNP analysis, the rs1031771 G allele (odds
      ratio=1.42, P=0.006) and rs1031772 T allele (odds ratio=1.40, P=0.018) were
      associated with a significantly higher risk of AHR. Haplotype analysis also
      detected significant association (P=0.006). Our findings suggest that SNPs
      located at the 3' downstream region of KCNS3 have a significant role in the
      etiology of AHR.

PMID- 15714334
TI  - Host factors in occupational diisocyanate asthma: a Swiss longitudinal study.
AB  - OBJECTIVE: To investigate the usefulness of surrogates for individual
      susceptibility to organic diisocyanates in occupational asthma. SUBJECTS: All new
      cases declared to the Swiss National Accident Insurance Company (SUVA) for
      establishment of a case for compensable occupational disease during 1993. Sixty
      nine persons, of whom three were women, were suspected of having occupational
      asthma due to isocyanates. Of these, 47 subjects fulfilled the criteria to be
      accepted as an occupational disease case. METHODS: All subjects were studied
      clinically and gave a blood sample for the phenotyping of their alpha-antitrypsin
      status and for immunological studies. The subjects were also given a peroral dose
      of caffeine for the determination of their N-acetylation capacity. Finally, those
      with an occupational disease were subjected to the methacholine provocation test.
      RESULTS: Forty-four persons with occupational disease, out of 47, were
      heterozygous antitrypsin carriers and/or slow acetylators of primary amines. In
      the bronchial provocation with methacholine, 12 of these subjects had an
      unaltered response and seven had a mild reaction, 13 a moderate one and 15 a
      severe reaction. INTERPRETATION: The study confirms the finding that slow N
      acetylators are susceptible to asthma from exposure to common diisocyanate
      monomers at work. The same applies to heterozygous antitrypsin-phenotype
      carriers. Thus, the use of these markers may reinforce the diagnostic procedure,
      but they cannot completely replace the immunological tests.

PMID- 15714335
TI  - Calcium stone disease: a multiform reality.
AB  - In calcium renal stones, calcium oxalate and calcium phosphate in various crystal
      forms and states of hydration can be identified. Calcium oxalate monohydrate
      (COM) or whewellite and calcium oxalate dihydrate (COD) or weddellite are the
      commonest constituents of calcium stones. Calcium oxalate stones may be pure or
      mixed, usually with calcium phosphate or sometimes with uric acid or ammonium
      urate. The aim of this study was to compare the clinical and urinary patterns of
      patients forming calcium stones of different composition according to infrared
      spectroscopic analysis in order to obtain an insight into their etiology. The
      stones of 84 consecutive calcium renal stone formers were examined by infrared
      spectroscopy. In each patient, a blood sample was drawn and analysed for serum
      biochemistry and a 24-h urine sample was collected and analysed for calcium,
      phosphate, oxalate, citrate and other electrolytes. We classified 49 patients as
      calcium oxalate monohydrate (COM) stone formers, 32 as calcium oxalate dihydrate
      (COD) stone formers and three as apatite stone formers according to the main
      component of their stones. Patients with COM stones were significantly older than
      patients with COD stones (P < 0.002). Mean daily urinary calcium and urinary
      saturation with respect to calcium oxalate were significantly lower in patients
      with COM than in those with COD stones (P < 0.000). Patients with calcium oxalate
      stones containing a urate component (< or = 10%) presented with higher saturation
      (P < 0.012) with respect to uric acid in their urine (and lower with respect to
      calcium oxalate and calcium phosphate, respectively P < 0.024 and P < 0.003) in
      comparison with patients without a urate component in the stone. Patients with
      calcium oxalate stones with a calcium phosphate component (> or = 15%) showed
      higher (P < 0.0016) urinary saturation levels with respect to calcium phosphate
      (and lower with respect to uric acid (P < 0.009), compared with patients forming
      stones without calcium phosphate or with a low calcium phosphate component.
      Patients with calcium stones mixed with urate had a significantly lower urinary
      pH (P < 0.002) and urinary calcium (P < 0.000), and patients with calcium
      phosphate >15%, higher urinary pH (P < 0.004) and urinary calcium (P < 0.000). In
      conclusion, in the evaluation of the individual stone patient, an accurate
      analysis of the stone showing its exact composition and the eventual presence of
      minor components of the stone is mandatory in order to plan the correct
      prophylactic treatment. Patients with "calcium stones" could require various
      approaches dependent on the form and hydration of the calcium crystals in their
      stones, and on the presence of "minor" crystalline components that could have
      acted as epitaxial factors.

PMID- 15714336
TI  - Concomitant physeal fractures of the distal femur and proximal tibia.
AB  - Concomitant physeal fractures of the distal femur and proximal tibia are very
      rare in children and adolescents. They are included in the classification of the
      "floating knee" injuries. Two cases with this combined injury are reported. They
      were closed injuries and in both patients the fracture of the proximal tibial
      epiphyseal plate was nondisplaced. In the first, a six-year-old girl, an early
      diagnosis was made radiographically. The intra-articular femoral fracture was
      operatively reduced and fixed. No growth abnormality was encountered 12 years
      later. The second patient, a 16-year-old boy, was conservatively treated for a
      displaced fracture-separation of the distal femoral epiphysis. Four weeks later
      there was physeal widening on both sides of the knee which indicated an
      associated fracture of the proximal tibial epiphyseal plate. One year after
      injury there was a varus deformity of the knee that was treated with a corrective
      osteotomy. Ten years later there is normal alignment of the leg.

PMID- 15714337
TI  - Primary chordoid meningioma of lung.
AB  - Primary meningiomas of the lung are rare. Most pulmonary meningiomas are typical
      syncytial or transitional meningiomas with smaller numbers of fibrous-type
      tumors. Herein, we report an unusual pulmonary tumor with the microscopic,
      immunohistochemical, and ultrastructural characteristics of a chordoid
      meningioma. The tumor was composed of cords and fascicles of small- to medium
      sized spindle and epithelioid cells with eosinophilic cytoplasm and round nuclei
      with finely dispersed chromatin. The tumor cells were surrounded by an abundant
      mucoid, vacuolated stroma. The periphery of the tumor was enveloped by a
      significant lymphoplasmacytic infiltrate. The neoplastic cells were positive for
      vimentin and epithelial membrane antigen only. The unusual morphology of the
      tumor caused significant diagnostic difficulties. The differential diagnosis
      included inflammatory myofibroblastic tumor, spindle cell myoepithelioma, and
      extraskeletal myxoid chondrosarcoma. To the best of our knowledge, this is
      possibly the first description of an extracranial or intrapulmonary chordoid
      meningioma.

PMID- 15714338
TI  - Molecular case report: IgVH analysis in acute humoral and cellular liver
      allograft rejection suggests a selected accumulation of effector B cells and
      plasma cells.
AB  - Acute cellular (CLR) and humoral liver allograft rejection (HLR) are the most
      important immunological obstacles to successful liver transplantation. In HLR,
      serum antibodies play the central pathogenetic role. In CLR, CD3+ T lymphocytes
      drive the destructive immune response. Although CLR and HLR show different
      clinical symptoms and can be kept apart in most cases, they share
      histomorphological similarities. In CLR, hepatic B lymphocytes and plasma cells
      as well as B-cell-activating cytokines have recently been described, indicating
      that, in addition to T cells, antibody-mediated mechanisms might be involved. To
      analyze the impact of hepatic B cells in CLR and HLR, the immunoglobulin (Ig)
      variable (V)-region gene repertoire was determined from tissue of one case of CLR
      and one case of HLR. Complement deposits and lymphocytic infiltrate were
      determined using immunohistochemistry. T cells, B lymphocytes and plasma cells
      could be detected in both cases, whereas C3c and C4d deposits could only be
      demonstrated in the HLR case. The molecular analysis of 63 V-region genes showed
      that B cells in both allografts expressed selected V-gene repertoires. All
      sequences differed from the putative germline sequences by multiple somatic
      mutations. This suggests a clonal expansion of selected effector B cells in the
      portal tracts of liver allografts. Locally accumulated B cells and their
      antibodies might be involved in IgG-mediated complement activation in CLR and
      HLR.

PMID- 15714339
TI  - A modified three-stage data envelopment analysis. The Netherlands.
AB  - In The Netherlands the care for the disabled accounts for 10% of total health
      care costs, or almost 1% of GNP. About half of these costs are devoted to the
      residential care for the mentally disabled. This study studied the amount of cost
      inefficiency in a sample of homes operating in 1998. We first apply a data
      envelopment analysis to our sample and then apply another stage-evaluating the
      nonradial slack of each input and the effects external factors have on them.
      After "correcting" for the external effects we find that technical and scale
      inefficiency disappears and cost efficiency increases by 6%. We attribute these
      findings with the strict regulation under which Dutch homes operate. Further,
      this approach can be applied to any service or market that faces governmental
      regulation.

PMID- 15714340
TI  - Side effects of generic competition?
AB  - This study examined the relationship between generic drug market shares and the
      number of reported side effects. Yearly time-series data for the number of
      reported side effects and information on market shares, prices, and quantities
      from 1972 to 1996 were used in this study. Poisson and negative binomial
      regression models were used in the statistical analysis. The results show that
      increased generic market share increases the number of reported side effects for
      all estimated models. When studying the relationship at the substance level,
      increasing generic market shares increases the number of side effects for 7 of
      the 15 substances. Generic substitution laws and measures to increase generic
      competition may thus have unintended consequences since these results show a
      positive relationship between generic market shares and reported side effects.

PMID- 15714341
TI  - Estimating rural households' willingness to pay for health insurance.
AB  - In many developing countries limited health budgets are a serious problem.
      Innovative ways to raise funds for the provision of health services, for example,
      through health care insurance, have a high priority. Health care insurance for
      rural households shields such patients from unexpected high costs of care.
      However, there are questions about whether, and how much, rural households are
      willing to pay to purchase such insurance, as well as the factors determining
      willingness to pay. In recent years the Iranian government has tried to improve
      health and medical services to rural areas through a health insurance program.
      This study was conducted to estimate rural households' demand and willingness to
      pay for health insurance. A contingent valuation method (CVM) was applied using
      an iterative bidding game technique. Data has been collected from a sample of
      2,139 households across the country.

PMID- 15714342
TI  - Measuring and comparing the (in)efficiency of German and Swiss hospitals.
AB  - A nonparametric data envelopment analysis (DEA) is performed on hospitals in the
      federal state of Saxony (Germany) and in Switzerland. This study is of interest
      from three points of view. First, contrary to most existing work, patient days
      are not treated as an output but as an input. Second, the usual DEA assumption of
      a homogeneous sample is tested and rejected for a large part of the observations.
      The proposed solution is to restrict DEA to comparable observations in the two
      countries. The finding continues to be that hospitals of Saxony have higher
      efficiency scores than their Swiss counterparts. The finding proves robust with
      regard to modifications of DEA that are motivated by differences in hospital
      planning in Germany and Switzerland.

PMID- 15714344
TI  - Economics and health promotion.
AB  - Health promotion activities consume a growing proportion of health sector
      spending in most developed countries. Yet, there is still considerable debate in
      the non-economic literature about exactly what health promotion constitutes and
      precisely how its role is to be conceived. This paper provides one economic
      answer to such questions. It sets out an argument that health promotion may be
      viewed, through the lens of traditional welfare economics, as a response to
      problems of market failure. A Grossman-type health investment model is invoked to
      analyse individual deviations from equilibrium and the possible instruments and
      targets of health promotion policy. The paper concludes by suggesting some of the
      alternative conceptual approaches that might be brought to bear, as well as some
      ideas for empirical research.

PMID- 15714343
TI  - Costs and consequences of botulinum toxin type A use. Management of children with
      cerebral palsy in Germany.
AB  - This study was a retrospective survey of the management of a cohort of children
      with cerebral palsy at Seepark Hospital, Germany, who did (cases; n=107) and did
      not (controls; n=107) receive botulinum toxin injections. Data on healthcare
      resource use and clinical outcomes over 12 months were collected from the date
      cases received their first injection and from the date controls were first
      admitted into hospital. Botulinum toxin use led to an 85% reduction in the number
      of children requiring surgery. Additionally, controls used significantly more
      healthcare resources than cases, particularly hospital bed days (69.2+/-34.1 vs.
      27.5+/-27.9 days; p <0.0001). The total cost of managing cases and controls was
      <euro>16,700 and <euro>33,800, respectively. In conclusion, use of botulinum
      toxin released resources for alternative use during the first year following
      treatment, without any loss of clinical improvement. However, it is unknown how
      botulinum toxin affected the need for surgery and associated outcomes in
      subsequent years.

PMID- 15714345
TI  - The cost structure of lung tuberculosis in Germany.
AB  - Although the total number appears to be decreasing, 7,886 new cases of
      tuberculosis (TB) were reported in Germany in 2001. Previous American
      publications reveal considerable differences in the costs caused by the disease.
      On the basis of the therapy guidelines of the Deutsches Zentralkomitee zur
      Bekampfung der Tuberkulose (DZK), this study estimates the mean direct outpatient
      and combined in- and outpatient costs of lung TB, together with the indirect
      costs of the disease on the basis of the most recent official health statistics.
      According to this, the mean outpatient costs per case were <euro>1,226 (adults)
      and <euro>785 (children under 15 years of age). The mean combined
      inpatient/outpatient costs ranged from <euro>14,301 (adults) to <euro>16,634
      (children). These are joined by the mean costs of sick benefit amounting to
      <euro>2,088. The mean indirect costs per case were <euro>2,461. Consistent
      implementation of the recommendations of the German DZK is still necessary in
      order to reduce the significant economic impact of TB disease resulting in high
      health and socioeconomic costs.

PMID- 15714346
TI  - Financing of health care services in Hungary.
AB  - In this paper we give a practical overview of the changes in the financing of
      health care in Hungary. We describe the financing system of general
      practitioners, home care (nursing), out-patient care and the acute and chronic
      care of hospitals. We show how the financial system has changed after the
      political changes of 1990. The global budget approach of the 1980s was replaced
      by performance-related financing methods including the ICPM (International
      Classification of Procedures in Medicine) code system of the WHO (World Health
      Organization) in out-patient care and the introduction of HBCS (Homogen
      Betegsegcsoportok, "Homogeneous Disease Groups") in in-patient care. We underline
      that the efforts made towards reforming health care financing resulted in an
      activity-related financing system.

PMID- 15714347
TI  - Reimbursement of glitazones in treatment of type 2 diabetes patients in Denmark
      in the context of a voluntary system for submitting pharmacoeconomic studies.
AB  - In 1998, guidelines for pharmacoeconomic evaluation were issued in Denmark. It
      was left to the discretion of the industry for which products to submit a
      pharmacoeconomic study. The impact of this voluntary system is illustrated by a
      case study on reimbursement of two types of glitazones. A review is presented of
      the evidence on safety, effectiveness and cost-effectiveness of glitazones that
      was available in the public domain at the time of reimbursement decision making,
      which was matched to the Danish criteria for general reimbursement of new
      pharmaceuticals. The study concludes that the voluntary system has not supported
      the inclusion of efficiency considerations in reimbursement decision making on
      glitazones. The decision-making process may be improved by mandatory
      pharmacoeconomic evaluations for selected products such as glitazones, which
      potentially represent a benefit to patients and potentially improve the cost
      effectiveness of care, while at the same time having a considerable budget
      impact.

PMID- 15714348
TI  - Costs of treatment of colorectal cancer in different settings in Germany.
AB  - The objective of this study was to evaluate the cost implications of different
      settings (inpatient, outpatient/day clinic, or office-based oncologists) for the
      administration of standard fluoropyrimidine therapies, i.e., Mayo Clinic and
      Arbeitsgemeinschaft Internistische Onkologie (AIO)/Ardalan regimen, and to
      compare the results with the cost of oral capecitabine in Germany. In total, 89
      quarterly fee-listings from 26 patients provided by 5 office-based oncologists
      were analyzed. Physician's services, drug costs, pharmacy costs, and costs for
      implantable venous port systems and single-use pumps were considered. Findings
      were transferred to the hospital setting. A third-party payer perspective was
      applied. Quarterly treatment costs for the Mayo Clinic regimen varied between
      <euro> 2,036 and <euro> 10,569, and between <euro> 1,294 and <euro> 10,179 for
      the AIO/Ardalan regimen depending on the treatment setting. Projected costs for
      capecitabine were <euro> 2,338. No hospitalization was considered to be necessary
      for capecitabine due to its oral administration route. The most expensive
      treatment options were the AIO/Ardalan protocol in the office-based setting and
      the Mayo Clinic protocol in the hospital setting. Capecitabine emerged as the
      cheapest option in the office-based setting. Overall, the cheapest option was the
      AIO/Ardalan protocol in municipal hospitals. However, municipal hospitals are
      unlikely to cover their costs in this situation. Substantial cost savings without
      incurring losses to providers may be realized if patients are transferred from
      the hospital setting to the office-based setting and treated with capecitabine.

PMID- 15714349
TI  - Out-patient drug policy by clinical assessment rather than financial constraints?
      The gate-keeping function of the out-patient drug reimbursement system in The
      Netherlands.
AB  - Since 1991, the Dutch Price Reference System (DPRS) has aimed at a growth
      reduction of out-patient drug costs without loss of medical quality. New drugs
      are excluded unless they pass legally anchored clinical criteria, i.e.
      substitutability with accepted drugs (DPRS-list 1a, implies a reimbursement
      maximum), 'unique and valuable' (DPRS-list 1b, liberal price setting), or lack of
      value (rejected). We analysed the performance (transparency, judgement stability)
      of the gate-keeping function during July 1999-July 2002. For drugs applied for
      DPRS-list 1b status, we relate the satisfaction of existing and implicit criteria
      to being accepted or rejected. Of 85 DPRS-list 1b applicants, 20 were shifted to
      DPRS-list 1a, 52 were accepted, and 13 were rejected with different roles of
      therapeutic value, budget impact, and burden of disease, the latter emerging as a
      decisive yet non-legal criterion. The gate-keeping function of the DPRS offers a
      non-opportunistic balance between clinical and economic demands, provided the
      burden of disease criterion is implemented, and provides influential tools for
      financial constraints.

PMID- 15714350
TI  - A pharmacoeconomic evaluation of the effects of atorvastatin on early recurrent
      ischemic events in acute coronary syndromes in Spain.
AB  - To determine the 16-week health economic outcomes of short-term, intensive lipid
      lowering therapy with atorvastatin in patients with acute coronary syndrome (ACS)
      using unit costs from Spain. The total expected cost per patient and the cost per
      inpatient event avoided were compared for patients on atorvastatin 80 mg daily
      versus placebo. The analysis was based on clinical outcome data from the MIRACL
      study. Clinical outcomes measured in this analysis included: death, cardiac
      arrest, nonfatal myocardial infarction (MI), fatal MI, angina pectoris, stroke,
      congestive heart failure (CHF), and surgical or percutaneous coronary
      revascularizations. Unit costs for outcomes were values using 2001 Diagnosis
      Related Group (DRG) costs in Spain. The cost of a follow-up visit was added to
      the cost of each outcome in both groups. In the atorvastatin group, monitoring
      costs were also added. All direct medical costs were taken from the perspective
      of the Spanish National Health System during a 16-week period. The hospital cost
      in the atorvastatin group was <euro> 1,921 per patient, compared to <euro> 1,853
      in the placebo group. The incremental cost per patient in the atorvastatin group
      was <euro> 67.47, corresponding to a cost per inpatient event avoided of <euro>
      1,760. The cost of atorvastatin for 16 weeks was <euro> 128. Forty-seven percent
      of this cost of atorvastatin was offset by the cost savings obtained through the
      reduction of number of events in the atorvastatin group. In Spain, the intensive
      short-term use of atorvastatin in patients with ACS has a favorable cost
      effectiveness. The direct cost of the drug was largely offset by the associated
      reduction in costs for treating fewer cardiovascular events.

PMID- 15714351
TI  - Long-term effects of supervised physical training in secondary prevention of low
      back pain.
AB  - BACKGROUND AND OBJECTIVES: In the last few years, several studies have focused on
      short-term treatment effects of exercise therapy. However, there is a lack of
      knowledge concerning the long-term treatment effects recorded after several
      years. Hence, this study was performed to investigate the short- and long-term
      effects of supervised physical training on functional ability, self-rated pain
      and disability in secondary prevention of low back pain. METHODS: One hundred and
      eighty-three hospital employees with chronic low back pain were randomly assigned
      either to back school (comparison group), or three-months supervised physical
      training including a back school (exercise group). Various measurements of
      functional ability were performed and subjects completed questionnaires on self
      rated pain, disability, and general well-being before treatment, immediately
      after intervention, and at six-months follow-up. At one-year and at ten-years
      follow-up participants evaluated treatment effectiveness. RESULTS: Out of 183
      employees, 148 completed the program. Participation at follow-ups ranged from 66
      to 96%. Supervised physical training significantly improved muscular endurance
      and isokinetic strength during a six-months follow-up, and effectively decreased
      self-rated pain and disability during a one-year follow-up. At ten-years follow
      up the subjects' assessment of the effectiveness of treatment was significantly
      better in the exercise group. CONCLUSIONS: Supervised physical training
      effectively improved functional capacity and decreased LBP and disability up to
      one-year follow-up. The subjects' positive evaluation of the treatment effect at
      ten-years follow-up suggests a long-term benefit of training.

PMID- 15714352
TI  - Air encephalography for hydrocephalus in the era of neuroendoscopy.
AB  - INTRODUCTION: There is often uncertainty regarding the site of the cerebrospinal
      fluid (CSF) block in individual patients with hydrocephalus, leading to a
      significant failure rate for endoscopic third ventriculostomy (ETV) when
      performed for unconventional pathologies such as postmeningitic and
      posthaemorrhagic hydrocephalus. We describe the use of lumbar air encephalography
      (AEG) to refine the indications for ETV in such circumstances. METHODS: Data from
      AEG studies used to guide indications for ETV were collected prospectively. The
      technique and protocol for AEG have been modified from the historical description
      of the procedure in the interest of safety and to minimise discomfort. In a
      separate evaluation, the level of the CSF block was determined by one of the
      authors, who was blinded to the results of the AEG, based on conventional
      computerised tomographic criteria. These results are compared with those obtained
      from the AEG. RESULTS: Forty-five studies were performed over a 2-year period.
      Thirty-seven were preinterventional, the majority of which demonstrated
      communicating hydrocephalus. ETV performed in five cases of non-communicating
      hydrocephalus was successful in each. The prediction of the level of block based
      on CT criteria was poor. CONCLUSION: It is often difficult to determine whether
      hydrocephalus is communicating or not with conventional imaging in the absence of
      a clearly demonstrable lesional obstruction to the CSF pathways. We have found
      AEG helpful in excluding patients with communicating hydrocephalus from an
      inappropriate ETV. On the basis of our experience, we consider the modified
      procedure safe as long as a strict protocol is followed.

PMID- 15714353
TI  - Surgical correction of metopic synostosis.
AB  - BACKGROUND: Premature closure of the metopic suture results in deformation of the
      anterior portion of the calvarium, which can vary from mild to severe. In mild
      forms, there is only prominent ridging of the metopic suture; more severe forms
      result in a marked narrowing of the frontal and temporal regions that in turn
      affects the supraorbital rims and produces hypotelorism. METHODS: The authors
      retrospectively reviewed 39 consecutive cases of metopic synostosis treated over
      a 12-year period. RESULTS: The average age at referral was 5 months, with surgery
      performed at an average age of 7.5 months. Fifteen infants had other congenital
      anomalies, with eight having synostosis of other sutures. Follow-up ranged from 7
      months to 6 years, with an average of 29 months. In three mild cases, burring of
      the metopic ridge was performed with excellent aesthetic results in all cases.
      The other 36 patients had significant deformity of the supraorbital ridges and
      temporal regions, with obvious hypotelorism for over 50% of the time. In these
      cases, the patients underwent craniofacial reconstruction to normalize their
      appearance. In addition, the lateral aspect of the sphenoid ridges, including the
      orbital roof and lateral orbital wall to the infraorbital fissure, was removed to
      free the cranial base. The average blood loss was under 400 ml and the average
      hospital stay was 3.6 days. Results were considered good to excellent in all
      except three cases, which had recurrence of a prominent metopic ridge; two
      required a second operation after 6 months for burring of this ridge, whereas the
      third was treated conservatively with an orthotic headband. CONCLUSION: Mild
      forms of metopic synostosis can be successfully treated with burring of the
      metopic ridge alone. Severe forms require craniofacial reconstruction and may be
      associated with other congenital abnormalities, additional synostosis, and
      developmental delay. In all cases, the operative procedure must be tailored to
      the nature and severity of the deformity.

PMID- 15714354
TI  - Simultaneous excision of two cerebral abscesses with the capsule.
AB  - CASE REPORT: A boy of 8 suffering from hemoglobinopathy M had two encapsulated
      cerebral abscesses confirmed on CT--one in the right temporal lobe, the second in
      the left frontal lobe--measuring 48 and 58 mm in diameter respectively. The
      disease began with fever, daily vomiting, and permanent somnolency, and was
      defined as encephalitis of viral etiology. TREATMENT: Conservative treatment
      proved ineffective and the patient's state grew worse. He underwent simultaneous
      excision of the two cerebral abscesses with a capsule. Continuous drainage of the
      operational cavities was performed. OUTCOME: The patient has been observed for 3
      months.

PMID- 15714355
TI  - Expression of terpenoid indole alkaloid biosynthetic pathway genes corresponds to
      accumulation of related alkaloids in Catharanthus roseus (L.) G. Don.
AB  - Madagascar periwinkle, Catharanthus roseus (L.) G. Don, a medicinally important
      plant, produces anticancer dimeric alkaloids, vinblastine and vincristine, in the
      leaves and accumulates antihypertensive alkaloids, ajmalicine and serpentine, in
      the roots. This plant grows wild in distant tropical and sub-tropical
      geographical locations with different agro-climates and shows wide variations in
      morphological and alkaloid yield-related traits. In order to understand the
      correlation between the expression of terpenoid indole alkaloid (TIA) pathway
      genes and accumulation of related alkaloids, six different genetic resources of
      C. roseus, including the medicinal cultivars Nirmal, Prabal, Dhawal, the mutants
      gsr-3 and gsr-6, and one horticultural variety, Pacifica blush, were studied. The
      expression profiles of one early and two late TIA biosynthetic pathway genes,
      namely, strictosidine synthase, desacetoxyvindoline 4-hydroxylase and deacetyl
      vindoline 4-O-acetyl transferase were analyzed in these plants. A positive
      correlation between transcript abundance and accumulation of related alkaloids
      was observed in the different genetic resources. The potential of these TIA
      biosynthetic pathway genes for use in screening of high-yielding C. roseus
      germplasm has been discussed.

PMID- 15714356
TI  - Plant blue-light receptors.

PMID- 15714357
TI  - [Osteonecrosis of the hip in adults].
AB  - Osteonecrosis of the hip (ON) in the adult is still an unsolved therapeutic
      problem. New pathophysiological findings have increased our knowledge of the
      disease course. Technical progress in imaging modalities and a better
      understanding of pathomorphology have improved the diagnostic procedure. The most
      significant progress for pathophysiology, early diagnosis and therapeutic
      decision making has been evolved by the routine use of MR-imaging. Using the
      international ARCO staging system, the pathomorphological and imaging changes
      during the different ON stages are described in this review. A diagnostic
      algorithm for ON is proposed. There are numerous conservative and surgical
      therapeutic approaches to ON, and the number of these is still increasing. A
      short overview of the most common therapeutic concepts is given. Finally,
      recommendations for therapeutic decision making for daily practice are proposed.

PMID- 15714358
TI  - Emesis induced by low or minimal emetic risk chemotherapy.
AB  - For patients treated with low or minimally emetogenic chemotherapy there is
      little evidence from clinical trials supporting the choice of a given antiemetic
      therapy or of any treatment at all. The panel recognized the necessity of
      considering the introduction into clinical practice of new agents in these
      categories, particularly oral cytotoxic agents and targeted biological agents and
      also the possibility of over-treatment with antiemetics. There was consensus
      among panel members regarding the recommended treatment for patients receiving
      chemotherapy agents with low and minimal emetic risk. Patients without a history
      of nausea and vomiting for whom minimally emetic risk chemotherapy is prescribed
      should not routinely receive antiemetic prophylaxis. A single agent such as a low
      dose corticosteroid is suggested for patients receiving agents of low emetic
      risk. If nausea and vomiting occurs during subsequent cycles of chemotherapy,
      prophylaxis with a single agent such as a substituted benzamide, a
      corticosteroid, or a phenothiazine should be administered. Only patients with
      persistent nausea and vomiting despite treatment with these recommended agents
      should receive a 5-HT3 receptor antagonist in the following cycles.

PMID- 15714359
TI  - The incidence of ischemic stroke versus intracerebral hemorrhage after carotid
      endarterectomy: a review of 2452 cases.
AB  - Carotid endarterectomy is a frequently performed vascular procedure. The most
      common major perioperative neurologic complication is ischemic stroke.
      Intracerebral hemorrhage has been traditionally viewed as less common. It has
      been recently proposed that as technical advances are made, the rate of ischemic
      stroke and other complications has decreased, causing hemorrhagic stroke to
      attain increasing importance as a perioperative complication. A review of 2452
      consecutive endarterectomies performed by a single surgeon from 1983 to 2000 was
      performed and rates of ischemic and hemorrhagic strokes were analyzed. There were
      five hemorrhagic strokes for a rate 0.20% (13.5% of postoperative neurologic
      complications) and 32 with ischemic strokes for a rate of 1.31% (86.5% of
      postoperative neurologic complications). From these data we conclude that
      hemorrhagic stroke remains uncommon and ischemic stroke continues to be the most
      frequent cause of postoperative neurologic complication after carotid
      endarterectomy.

PMID- 15714360
TI  - Spontaneous dissection of the extracranial vertebral artery: indications and long
      term outcome of surgical treatment.
AB  - Spontaneous dissection of the vertebral artery (VA) is usually managed medically.
      The objective of this report was to describe 10 patients treated surgically for
      spontaneous dissection of the VA. Seven men and three women with a mean age of
      52.5 +/- 11.3 years were treated between December 1978 and January 2001. In eight
      cases the presenting symptom was neck pain. Transient ischemic attack or
      completed stroke in the vertebrobasilar distribution followed in nine cases. In
      the remaining case, symptoms resulted from irritation of the superior roots of
      the brachial plexus. Dissection was located in one segment of the VA in seven
      cases and two contiguous segments in three cases. Lesions involved aneurysm in
      seven cases, tight stenosis in two, and occlusion in one. The decision to perform
      surgery was made because of either continued symptoms despite maximal
      anticoagulation therapy or the presence of an aneurysm causing recurrent
      thromboembolism or threatening rupture. In eight cases the revascularization
      procedure consisted of bypass from the carotid artery to the distal VA. In the
      remaining two cases revascularization was achieved by transposition of the VA
      directly onto the common or internal carotid artery. Postoperative recovery was
      uneventful in all cases. No further neurological events were observed in any
      patient at a mean follow-up of 96.9 +/- 66 months (range, 12-216 months). Long
      term resolution of vertebrobasilar symptoms was achieved in all cases, including
      one patient whose bypass occluded at 6 months. From these results we conclude
      that surgical treatment is the method of choice for spontaneous dissection of the
      extracranial VA associated with continued vertebrobasilar symptoms despite
      maximal medical therapy or with an expanding aneurysm. The most useful technique
      is bypass to the distal VA. Morbidity is low and long-term outcome is excellent.

PMID- 15714361
TI  - Acute carotid artery thrombosis: description of 12 surgically treated cases.
AB  - The morbidity and mortality of stroke secondary to acute internal carotid artery
      thrombosis range from 40 to 69% and from 15 to 55%, respectively, after purely
      medical treatment. This report describes a series of 12 patients who underwent
      urgent surgical treatment for primary acute carotid artery thrombosis between
      January 1999 and December 2002. Upon admission, all patients had severe
      neurologic deficits contralateral to carotid artery thrombosis. One patient
      experienced ongoing changes in the level of consciousness. The interval between
      the onset of symptoms and admission was less than 6 hr in all cases. Initial work
      up in all patients included a brain computed tomographic scan with contrast
      injection and carotid duplex scan. The operative procedure consisted of carotid
      thomboemdarterectomy after shunt placement with prosthetic patch closure.
      Intraoperative angiography was performed in all cases. Following treatment, we
      observed deterioration of neurologic status leading to death in one case;
      improvement with partial regression of initial neurologic deficit in two cases,
      including one patient who died from causes unrelated to carotid artery disease;
      and full neurologic recovery in nine cases. The delay to revascularization was
      longer than 6 hr in both patients who died. These data support surgical
      intervention for carotid artery thrombosis in selected patients without major
      disturbances of consciousness or hemorrhagic infarction, provided that the delay
      to revascularization is less than 6 hr.

PMID- 15714362
TI  - Transcranial Doppler monitoring after carotid endarterectomy.
AB  - The objectives of this study were to evaluate the feasibility of transcranial
      Doppler (TCD) monitoring after carotid endarterectomy (CEA) and to investigate
      whether 1 hr of monitoring is sufficient to detect a clinically relevant change
      in the number of postoperative microemboli. We also evaluated the association of
      patient characteristics and procedure-related variables with the number of
      postoperative microemboli. One hundred and two patients were monitored during the
      second hour after CEA. The main outcome measure was the number of TCD-detected
      microemboli. The secondary outcome measure was a procedure-related cerebral
      complication graded according to the modified Rankin scale. The median number of
      microemboli during the second postoperative hour was two (interquartile ranges,
      0.75-11) and decreased in most the patients during this time. Two patients had a
      relatively high and increasing number of microemboli and developed a minor stroke
      after a symptom-free interval. One patient developed a TIA intraoperatively.
      There was no significant association between patient characteristics and the use
      of a venous patch and the number of postoperative microemboli. Conversely, a
      statistically significant negative association was found between shunt use and
      the number of microemboli (p = 0.02). The majority of patients had no or a small
      and decreasing number of microemboli. One hour of monitoring appeared to be
      effective to select those patients in whom the number of microemboli did not
      spontaneously decrease and who may need additional medical treatment or surgical
      reexploration. The role of TCD-detected microemboli as a surrogate measure for
      the risk of stroke after CEA remains to be validated.

PMID- 15714363
TI  - Post-traumatic thoracic outlet syndromes.
AB  - This retrospective study aims to clarify the mechanisms, frequency, symptoms,
      treatment, and outcome of post-traumatic thoracic outlet syndromes. A total of 13
      patients (7 men and 6 women) with a mean age of 41 +/- 16 years were studied.
      Underlying injuries resulted from sports, road, and household accidents. Bone
      lesions were pseudarthrosis, hypertrophic callus, and luxations. Congenital
      anomalies were observed in five patients (38%). Vascular lesions included
      aneurysm of the subclavian artery or vein, acute ischemia, and subclavian vein
      thrombosis. Operative treatment involving orthopedic and/or vascular surgery was
      indicated in all patients. Post-traumatic thoracic outlet syndrome occurs in
      young subjects after violent trauma. Vascular complications are frequent and
      severe. Treatment achieves good results but benefits may be diminished by bone or
      nerve involvement.

PMID- 15714364
TI  - Ruptured abdominal aortic aneurysms: factors influencing early survival.
AB  - In this study we aimed to define relevant prognostic predictors for the outcome
      of surgical treatment of ruptured abdominal aortic aneurysms. The study included
      406 consecutive patients treated between January 1991 and December 2003. There
      were 337 (83%) male and 69 (17%) female patients aged 67 +/- 7.5 years. Fourteen
      (3.5%) patients had aortocaval fistula whereas 4 (0.98%) had primary
      aortorenteric fistula caused by aneurysm rupture into the inferior vena cava or
      duodenum. Reconstruction included interposition of a tube graft (215-53%),
      aortobiiliac bypass (134-33%), and aortobifemoral bypass (58-14.3%). Findings on
      admission that significantly correlated with both intraoperative (13.5%) and
      total operative mortality (48.3%) were systolic blood pressure <95 mmHg, low
      diuresis, unconsciousness, cardiac arrest, leukocytes >14 x 10(9)/L, hematocrit
      <0.29%, hemoglobin <100 g/L, urea> 11 mmol/L, and creatinine >180 micromol/L.
      Intraoperative determinants of increased mortality were aortic cross-clamping
      time >47 min, duration of surgery >200 min, intraoperative blood loss >3500 mL,
      diuresis <400 mL, arterial systolic pressure <97.5 mmHg, and the need for
      aortobifemoral bypass. Respiratory complications and multisystem organ failure
      were significantly associated with lethal outcome in the postoperative period.
      Surgical treatment of ruptured abdominal aortic aneurysm was life-saving in 51.7%
      of patients. Variables significantly associated with mortality were
      unconsciousness, low systolic blood pressure, cardiac arrest, low diuresis, high
      urea and creatinine levels, signs of blood loss, and the need for aortobifemoral
      reconstruction. Short aortic cross-clamping and the total operation time, low
      intraoperative blood loss, and well-controlled diuresis and arterial pressure
      during surgery have improved survival. Therapeutic efforts should concentrate on
      intraoperative factors that are possible to correct, leading to better survival
      of these patients.

PMID- 15714365
TI  - Hospital readmissions following abdominal aortic aneurysm repair.
AB  - In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are
      well described. However, little is known about post-discharge readmission rates,
      lengths of stay, associated mortality, and costs. We examined 206 consecutive
      patients who underwent AAA repair at two American hospitals between 1998 and
      2000. Index hospitalization and 6-month readmission data were extracted from a
      resource and cost accounting system used by both hospitals. Among the 206
      patients, 183 survived until discharge (mortality rate 11.2%). Among the
      surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the
      readmissions occurred within two weeks of discharge, with patients presenting
      with a diverse array of complications. Nonelective repair and diabetes mellitus
      were independent predictors of hospital readmission (OR = 2.83, 95% CI = 1.25
      6.40, p = 0.01; OR = 6.60, 95% CI = 1.02-42.4, p = 0.047, respectively). For each
      readmission, the mean length of stay was 10.7 +/- 2.5 days and the mean cost was
      dollar 13,397 +/- 3,381. The cumulative number of hospital days during the 6
      months post-discharge was 17.7 +/- 3.5 days for each readmitted patient and the
      mean per-patient total cost was dollar 23,262 +/- 5,478. The mortality rate among
      readmitted patients was 13.2%. Overall, readmissions following AAA repair
      accounted for a cost >50% over and above the cost of the readmitted patients'
      index hospitalization. Hospital readmissions are common during the 6 months
      following AAA repair. Patients who are readmitted experience long lengths of stay
      and high mortality rates, and their care incurs high costs.

PMID- 15714366
TI  - Visceral artery aneurysms.
AB  - Visceral artery aneurysms (VAA) frequently present as life-threatening
      emergencies. The purpose of this study was to review our experience with VAA
      treatment. Between 1988 and April 2002, 31 VAA were treated in 28 patients (14
      males, 14 females) with average age of 55 +/- 15 years. The most common locations
      were the splenic artery (16) and the hepatic artery (7). Three patients underwent
      emergency surgery, 22 patients had elective open surgery, and 7 patients
      underwent endovascular treatment. In the surgical group the perioperative
      mortality rate was 3.6%. The perioperative morbidity rate was 7.1% (one case of
      respiratory distress manifested in the immediate postoperative period and one
      urgent case of bilious fistula). In the endovascular group none of the patients
      died; the perioperative morbidity rate was of 14.3% (one case of hepatic artery
      thrombosis after failure of gastroduodenal artery aneurysm embolization). Failure
      of the procedure was 42.9% (3 cases of aneurysm recanalization). In conclusion,
      we believe that an aggressive surgical approach is justified, even in the case of
      asymptomatic VAA, because of the low morbidity and mortality rates. Endovascular
      treatment should be reserved for selected cases.

PMID- 15714367
TI  - Comparison of precuffed and vein-cuffed expanded polytetrafluoroethylene grafts
      for infragenicular arterial reconstructions: a case-matched study.
AB  - Distal vein cuff interposition is often added to prosthetic infragenicular
      arterial reconstruction in an attempt to improve hemodynamics and patency rates.
      The purpose of this study was to compare the outcome of a precuffed expanded
      polytetrafluroethylene (ePTFE) graft with a vein-cuffed ePTFE graft for
      infragenicular bypass. We reviewed the clinical outcome of 77 patients with
      critical limb ischemia without available autologous vein conduits who underwent
      arterial reconstruction of 80 limbs to below-knee popliteal or tibioperoneal
      vessels using either ePTFE precuffed graft (precuffed group, 38 patients 40
      limbs) or ePTFE vein-cuffed graft (vein-cuffed group, 39 patient, 40 limbs).
      Precuffed group patients were enrolled in a prospective cohort study. Vein-cuffed
      group patients consisted of consecutive case-matched patients operated on during
      the same study period. End points were primary graft patency and limb salvage
      rates. There were 42 males and 35 females with a mean age of 73.4 years (range,
      44-92 years). Both groups were matched to demographics, risk factors for
      atherosclerosis, previous ipsilateral reconstruction, and location of the distal
      anastomosis. Proximal anastomosis was to the common (n = 68) or superficial (n =
      12) femoral arteries. Distal anastomosis was to the below-knee popliteal (n =
      28), anterior tibial (n = 12), posterior tibial (n = 15) and peroneal (n = 25)
      arteries. Operative mortality was 1.3%. Graft patency at dismissal was 90% and
      95% in the precuffed and vein-cuffed groups, respectively. The mean follow-up was
      25.7 months (range, 2.4-61 months). Primary patency rates at 1 and 3 years were
      70% and 57% in the precuffed group, and 78% and 54% in the vein-cuffed group (p =
      0.32). Limb salvage rates at 1 and 3 years were 97% and 70% in the precuffed
      group, and 95% and 81% in the vein-cuffed group (p = 0.49). Overall patient
      survival at 1 and 3 years was 81 % and 57%, respectively. In this case-control
      study, results of precuffed ePTFE graft were similar to those obtained with vein
      cuffed ePTFE grafts. The precuffed ePTFE graft is an adequate alternative conduit
      for infragenicular arterial reconstruction in patients with critical limb
      ischemia and no available autologous veins.

PMID- 15714368
TI  - Timing of pedal bypass failure and its impact on the need for amputation.
AB  - Although the utility of dorsalis pedis (DP) bypass for limb ischemia has been
      well established, the fate of limbs with a failed bypass to the DP artery remains
      unclear. Data of all patients undergoing DP bypass grafting within a 12-year
      period from two university hospitals' vascular registries were retrospectively
      reviewed. Outcomes of early (<30 days) and delayed graft failure (>30 days) were
      examined. The Student's t-test and chi-squared test were used for univariate
      analysis; patency rates and patient survival were calculated using the Kaplan
      Meier product limit method. Of 1434 DP bypass grafts, 277 (19.3%) failed grafts
      were identified. Sixty five (4.5%) grafts failed early (within 30 days of
      surgery) and 212 (14.8%) failed late at a mean time of 15.3 months (range, 1.5
      105 months) after initial bypass. Of the 65 limbs with early graft failure, 28
      (43.1%) proceeded directly to amputation and 20 underwent additional
      revascularization attempts, but limb salvage was achieved in only 7 patients; in
      45 (69.2%) patients no further revascularizations were attempted. Seventy-four
      (34.9%) patients with late graft failure underwent redo revascularization. Thirty
      nine (52.6%) had their limb saved with graft revision, but 35 patients (47.3%)
      ultimately lost their limb. In 138 patients with late graft failure (65.1%) no
      further revascularization attempts were performed. Sixty-two (44.9%) required
      major amputation. Overall, 49.8% of patients with failed pedal grafts ultimately
      suffered limb loss. Early graft failure resulted in a significantly higher rate
      of major amputation that did late graft failure (63.1% vs. 45.8%, respectively; p
      = 0.015). These results indicate that early occlusion of pedal bypass often leads
      to immediate major amputation and interventions to maintain graft patency in this
      setting are often futile. Late failure of pedal bypass is associated with a lower
      likelihood of amputation because of a higher rate of success of bypass revisions
      and a lower occurrence of critical ischemia with graft failure.

PMID- 15714369
TI  - Tibial angioplasty as an alternative strategy in patients with limb-threatening
      ischemia.
AB  - The purpose of this study was to assess the technical feasibility and early
      outcome of tibial angioplasty for a subset of patients with limb-threatening
      ischemia who were not candidates for bypass grafting. A retrospective analysis
      was conducted of 19 patients (7 male, 12 female) who underwent crural angioplasty
      for limb-threatening ischemia using 0.018- or 0.014 inch-based systems.
      Contraindications to bypass were insufficient conduit in 7 patients and severe
      comorbid illness in 12. Concurrent treatment of inflow lesions was performed in
      12 of 20 limbs via either angioplasty alone (5) or combined with stenting (12).
      Outcome measures were ankle-brachial indices (ABI), relief of rest pain, and
      healing or healed wounds. Twenty-three vessels were treated, including 14 tibial
      occlusions and 9 stenoses. The average length of diseased segment was 11 cm
      (range, 3-25 cm). Thirteen of 14 occlusions were treated with subintimal
      recanalization, the remainder with laser recanalization. Technical success was
      achieved in 22 of 23 treated vessels. Mean preoperative ABI was 0.53 and mean
      postoperative ABI was 0.85. Palpable pulses were present in 11 of 20 limbs (55%).
      There was one perioperative mortality (5.2%). Mean follow-up was 3 months. Three
      failures occurred requiring amputation (15.8%). The remaining 16 patients were
      improved with healing (8) or healed (4) wounds and relief of rest pain (4). These
      results indicate that technical success may be achieved with outflow lesion
      angioplasty in the majority of patients encountered. The durability of this
      method of therapy is unknown, and our length of follow-up is not sufficient to
      answer this question. However, an attempt at angioplasty appears justified before
      primary amputation and before surgical bypass in those patients at high risk for
      intervention.

PMID- 15714370
TI  - Lower extremity superficial venous aneurysms.
AB  - Venous aneurysms are not rare. But most attention has been paid to deep venous
      aneurysms. Because of their propensity to thrombose and cause pulmonary
      embolization. Increased availability of duplex Doppler ultrasound has allowed
      total evaluation of all venous segments in patients undergoing surgery for
      chronic venous insufficiency. In this study, patients were recorded consecutively
      and the venous reflux examination was carried out with the patient standing. The
      superficial venous system was studied with special interrogation of the great and
      small saphenous veins and their tributaries. Reflux >0.5 sec was recorded as
      positive. Data were analyzed using the Spearman's correlation index and the
      student's t-test. A strong correlation was considered for values of rho > 0.6. A
      total of 65 superficial venous aneurysms of the saphenous vein systems were found
      in 43 patients (33 women and 10 men) with an average age of 53 years (range, 34
      70). The mean body mass index (BMI) overall was 25 +/- 4.6. The BMI in men was
      29.5 +/- 2.5. The BMI in women was 23.6 +/- 4 (p < 0.05). Aneurysms of the
      saphenous systems were classified into four types. Type I aneurysms (52%) were
      located in the proximal third of the saphenous vein, not at the saphenofemoral
      junction but instead just distal to the subterminal valve. Type II aneurysms were
      located in the shaft of the saphenous vein in the distal third of the thigh
      (35%). The third classification (type III) of superficial saphenous vein
      aneurysms was an occurrence of types I and II in the same lower extremity (3
      patients/43 patients). Superficial venous aneurysms of the short saphenous system
      were found and were classified as type IV (6%.) Strong correlations were found
      with female gender and a very strong correlation of larger aneurysms was found
      with an elevated BMI in men. There was a so a strong correlation between type III
      aneurysms of the proximal and distal thigh greater saphenous vein and greater
      saphenous vein reflux. Aneurysms of the saphenous veins are common and this may
      have an impact on choice of surgical treatment.

PMID- 15714371
TI  - Comparing short-term outcomes of femoral-popliteal and iliofemoral deep venous
      thrombosis: early lysis and development of reflux.
AB  - This study compares the development of reflux, recanalization, and clinical
      outcomes of patients with femoral-popliteal and iliofemoral deep venous
      thrombosis (DVT). Emphasis is placed on the relationship between early lysis of
      clot through thrombolysis and the development of reflux and post-thrombotic
      syndrome (PTS) for iliofemoral patients. A retrospective chart review was
      conducted of 27 femoral-popliteal DVT limbs and 11 iliofemoral DVT limbs with
      average follow-up of 2.3 and 2.1 years, respectively. Rates of recanalization,
      development of reflux, and post-thrombotic syndrome were recorded through review
      of duplex scans and physical examinations. All femoral-popliteal patients
      received anticoagulant therapy. Nine of 11 iliofemoral patients (82%) received
      thrombolytic therapy in addition to anticoagulants. Statistical analysis included
      Kaplan-Meier estimation to take into account dropout in follow-up times, and chi
      squared analysis to compare final outcomes. A significantly greater proportion of
      iliofemoral patients (73%) than femoral patients (31%) remained asymptomatic at
      the end of their follow-up (p < 0.025). Because of thrombolytic therapy, 82% of
      iliofemoral limbs showed partial or complete lysis 4 weeks after diagnosis of
      clot. As expected, only 22% of femoral-popliteal limbs developed some
      recanalization 4 weeks after diagnosis (p < 0.005). Interestingly, no significant
      difference in reflux development was observed between the two groups. After an
      average of 2.1 years, 60% of femoral-popliteal limbs developed reflux in the deep
      veins vs. 64% for iliofemoral limbs. The iliofemoral DVT patients showed improved
      clinical outcomes in the short term compared to that of femoral-popliteal
      patients in this pilot study. The improved clinical outcomes could be attributed
      to the early lysis of clot via thrombolytic therapy for the iliofemoral group.
      Although the extent of reflux development was similar in both groups, iliofemoral
      patients still showed fewer clinical symptoms after follow-up. This may suggest
      that the presence of both residual obstruction and reflux, rather than either one
      alone, significantly increases the chances for development of PTS. Since
      thrombolytics eliminates at least one of these factors, residual obstruction, it
      may aid in decreasing development of PTS in the short term. The data in this
      retrospective study warrant further long-term prospective analysis of
      thrombolysis and its relationship with PTS.

PMID- 15714372
TI  - Pulsatility index of temporal and renal arteries as an early finding of
      arteriopathy in diabetic patients.
AB  - The objective of this study was to investigate the relationship between
      alterations in the elasticity of the temporal and the renal arteries and the
      grade of arteriopathy, using the pulsatility index in type II diabetic patients
      and healthy volunteers. All individuals were divided into groups. Group A
      consisted of 15 patients without risk factors (hyperlipidemia, hypertension,
      obesity, and smoking) and had well-controlled diabetes mellitus as demonstrated
      by normal values of HbA1c. Group B had 20 patients with two risk factors
      (hyperlipidemia and hypertension) and normal HbA1c. Group C (25 patients) had
      four risk factors and high values of HbA1c, and group D consisted of 20 healthy
      individuals. All patients were examined by use of color Doppler ultrasonography.
      Pulsatility index values were measured in the temporal and renal arteries.
      Pulsatility indices of temporal arteries were higher in group C than in groups A
      and B, whereas for the renal arteries, no significant difference was detected
      between the four groups. In our study there seems to be strong correlation
      between increased values of pulsatility index, mainly in the temporal arteries,
      and grade of arteriopathy in type II diabetic patients.

PMID- 15714373
TI  - Partial excision of infected fistula results in increased patency at the cost of
      increased risk of recurrent infection.
AB  - Reliable vascular access is often an issue of ongoing frustration for those
      requiring dialysis. Synthetic arteriovenous fistulae (SAVF) have been widely used
      to provide vascular access; however, the risk of infection at the SAVF site is
      significant, especially because the SAVF is potentially exposed to pathogens on a
      regular basis due to the cannulation required for dialysis. Between 11 and 35% of
      all SAVF become infected and require surgical removal. The purpose of this
      investigation was to: (1) compare the risk of recurrent infection with complete
      versus partial excision of the infected SAVF (ISAVF) and (2) explore the risks
      and benefits of attempting to preserve patency of noninfected portions of ISAVF.
      In a retrospective review to determine the risk of recurrent infection after
      removal of ISAVF, charts of 77 patients undergoing surgery for the removal of an
      ISAVF from the arm were identified with 84 instances of excision of an ISAVF. Of
      the 84 ISAVF, 26 (31 %) were treated with complete excision (CE), 30 (35.7%)
      grafts were partially excised with blood flow restoration through a new
      interposed PTFE segment (PERF), and 28 (33.3%) grafts were partially excised with
      no flow restoration (PENF), leaving portions that were not grossly infected.
      Fourteen of 30 (46.7%) PERF grafts, 4/28 (14.3%) PENF, and 0/26 CE grafts
      developed further infection at the excision site. These differences were
      significant when comparing PERF to CE (p < 0.001) and PERF to PENF (p < 0.025),
      but no significance was found when comparing CE to PENF. Patency was
      significantly greater for the PERF group at 1 and 2 years than for both CE (p <
      0.001) and PENF (p < 0.001). In conclusion, the data suggest that restoring blood
      flow to the remainder of a partially excised ISAVF significantly increases
      patency without necessitating catherer placement and a new hemoaccess site, but
      at the cost of significantly increased risk of recurrent infection.

PMID- 15714374
TI  - Infected pseudoaneurysm of the femoral artery secondary to melioidosis infection
      of a previous femoropopliteal bypass graft.
AB  - Infected arterial aneurysm or pseudoaneurysm caused by Burkholderia pseudomallei
      is very rare; a review of the literature reveals only five previously reported
      cases. We report the first case of melioidosis infection of a previous
      femoropopliteal bypass graft complicated by para-anastomotic pseudoaneurysm of
      the femoral artery successfully treated by surgical removal of the old graft and
      creation of a new, extraanatomic, external iliac-to-popliteal bypass graft.

PMID- 15714375
TI  - Endovascular repair in the presence of aortic infection.
AB  - The purpose of this study is to describe our experience in the endovascular
      management of two cases of aortoenteric and aortoesophageal fistula that were
      unsuccessfully treated with an aortic stent graft because of recurrent infection.
      Although endovascular repair appears to be a promising therapeutic modality, in
      the presence of infection this technique should be considered on an individual
      basis. Failure of treatment should be expected in a significant number of cases
      during follow-up, particularly in patients with signs of sepsis. A review of the
      literature with positive and negative results has been included for a better
      understanding of this condition.

PMID- 15714376
TI  - Endovascular therapy for tracheoinnominate artery fistula: a temporizing measure.
AB  - Tracheoinnominate artery fistula remains an uncommon, highly fatal complication
      of tracheostomy and peritracheal pathology. Endovascular placement of a covered
      stent can provide control of the fistula. Depending on the conditions of the
      trachea and peritracheal tissues, the fistula may heal or the stent may become
      infected and/or further erode into the trachea. We report on a case of a patient
      with a tracheoinnominate artery fistula related to peritracheal tumor invasion,
      radiation therapy, and tracheostomy. The fistula was initially excluded with a
      covered stent, but a few weeks later hemoptysis recurred secondary to deep
      tracheal erosion by the covered stent.

PMID- 15714377
TI  - Staged open and endovascular repair of thoracoabdominal aneurysms using the
      common carotid artery.
AB  - The purpose of this study was to demonstrate the feasibility of staged open and
      endoluminal repair of complex thoracoabdominal aneurysms. We report the
      management of two patients with a staged, open abdominal and endoluminal thoracic
      repair of Crawford extent II aneurysms, where iliofemoral access was impossible
      and thoracic repair effected by endograft deployment via a common carotid artery.
      From this experience we conclude that staged open and endovascular repair for
      both ruptured and elective Crawford extent II thoracoabdominal aneurysms can be
      performed using the common carotid artery, when anatomy is favorable.

PMID- 15714378
TI  - Intrathrombotic pressure of a thrombosed abdominal aortic aneurysm.
AB  - In a case of thrombosed abdominal aortic aneurysm, intraluminal and
      intrathrombotic pressures were simultaneously measured 3 cm distal to the left
      renal vein level (#1), at the inferior mesenteric artery level (#2) (3 cm distal
      to #1), 3 cm distal to #2 (#3), and at the aortic bifurcation level (#4) (3 cm
      distal to #3). The intraluminal pressure (at #1) was 154/72 (101) mmHg, and the
      intrathrombotic pressures at #2, #3, and #4 were 138/77 (100), 137/74 (97), and
      135/68 (96) mmHg, respectively. The percentages of the systolic and mean
      intrathrombotic pressures to the intraluminal pressure were 90% and 99% at #2,
      89% and 96% at #3, and 88% and 95% at #4, respectively. The mural thrombus of an
      aneurysm does not significantly decrease the pressure on the aneurysmal wall,
      even in a thrombosed aneurysm.

PMID- 15714379
TI  - Celiac artery aneurysm embolization by coil occlusion.
AB  - We present here an extremely rare case of celiac artery aneurysm treated by
      embolization coil occlusion and review the literature on celiac artery aneurysm
      and its treatment. This case documents how celiac artery aneurysms can be
      successfully treated in a single setting with a good long-term outcome. In this
      unique case the technical and clinical details specific to this very complex and
      unusual aneurysm embolization are highlighted.

PMID- 15714380
TI  - Acute thrombosis of inferior vena cava in a pregnant woman presenting with
      sciatica: a case report.
AB  - A 20-year-old pregnant woman was admitted to our department with symptoms of deep
      venous thrombosis in the left lower extremity and excessive lumbar pain. Low
      molecular-weight heparin was administered. She recovered with this treatment,
      however, severe lumbar pain continued. A lumbar magnetic resonance image showed
      dilated epidural veins compressing the roots and acute thrombosis of the inferior
      vena cava extending to renal veins. During the same period she had acute deep
      venous thrombosis in her right leg. An urgent venous thrombectomy was performed.
      Sciatica and deep venous thrombosis resolved after the operation. Low-molecular
      weight heparin was administered until the end of her pregnancy.

PMID- 15714381
TI  - Anesthesia technique and outcomes of endovascular aneurysm repair.
AB  - Anesthetic techniques vary widely in the endovascular repair of abdominal aortic
      aneurysms (EVAR). Previous studies have demonstrated the feasibility of using
      local anesthesia. However, the ideal anesthetic technique has not been
      determined. This study examines whether anesthetic technique influences the
      outcomes of EVAR. Data regarding demographics, risk factors, procedural
      characteristics, recovery characteristics, treatment complications, acute (<30
      day) medical complications, mortality, and anesthetic type were prospectively
      collected during the AneuRx phase II aortic endograft trial. Patient cohorts
      receiving general, regional, or local anesthesia were compared. From 1997 to
      1998, 424 patients underwent EVAR at 13 sites using the AneuRx Bifurcated
      endograft. There were 279 patients in the general anesthesia group, 95 patients
      in the regional group, and 50 patients in the local group. Risk factors were
      similar. There were no significant differences in age, gender, American Society
      of Anesthesiologists grade, length of anesthesia, branch artery occlusions,
      proximal endoleaks, failed implants, or open surgical conversions. Cardiac,
      renal, and wound-healing complications were all lower in the local group.
      Mortality was equivalent among the three groups. (p > 0.05, ANOVA). From these
      results we concluded that EVAR with local anesthesia is a safe and efficacious
      method that may reduce recovery times and postoperative medical morbidity
      compared to use of general or spinal/epidural anesthesia.

PMID- 15714382
TI  - Atherosclerosis as inflammation.
AB  - Atherosclerosis has traditionally been attributed to disordered cholesterol
      metabolism with associated accumulation of lipid substrate in the arterial wall.
      It is now believed that systemic and local inflammatory events mediate all phases
      of plaque development, progression, and degeneration. No longer regarded as a
      bland, mechanical process, plaque evolution is now best understood as a pitched
      battle between proinflammatory and anti-inflammatory cellular and molecular
      elements. Not unlike models of chronic wound healing or ischemia-reperfusion, the
      biologic state of a plaque at any given time is transient and mutable, reflecting
      a dynamic balance of numerous local and circulating inflammatory forces. Dreaded
      complications of the disease such as myocardial infarction and stroke result from
      acute shifts in this balance in favor of plaque instability and vulnerability
      over stable states of chronic inflammation. The purpose of this article is (1) to
      review the inflammatory pathogenesis of atherosclerosis on a molecular basis, (2)
      describe several of the emerging inflammatory biomarkers currently being
      investigated with particular interest in their possible roles as direct mediators
      of vascular disease, and (3) identify several important implications for
      diagnosis and therapy.

PMID- 15714385
TI  - Progesterone receptor antagonists and selective progesterone receptor modulators
      (SPRMs).

PMID- 15714383
TI  - Splenic infarction in a pregnant woman with systemic lupus erythematosus.
AB  - Here we describe a 20-year-old pregnant woman with systemic lupus erythematosus
      who had high anticardiolipin antibodies and presented with splenic infarction.

PMID- 15714386
TI  - Mechanisms controlling agonist and antagonist potential of selective progesterone
      receptor modulators (SPRMs).
AB  - Progesterone exhibits diverse biological activities, inducing proliferation of
      the mammary gland epithelium, but it opposes the mitogenic activity of estrogen
      in the uterus. These tissue-selective activities of progesterone are mediated by
      the progesterone receptor (PR), a member of the nuclear receptor superfamily of
      ligand-dependent transcription factors. Several clinically useful PR antagonists
      that block progesterone activity have been described, yet some of these compounds
      exhibit tissue-selective partial agonist activity, leading them to be termed
      selective progesterone receptor modulators (SPRMs). This partial agonist activity
      is mediated primarily through the N-domain of the B isoform of PR, although the
      mechanism has not yet been defined. In this review, we discuss mechanisms by
      which PR activates transcription and ways in which antagonists oppose
      progesterone activity. We discuss mechanisms by which the N-domain mediates
      tissue specific partial agonist activity of SPRMs, as well as receptor
      interacting coregulatory proteins that influence this activity of the N-domain.
      We also describe newly developed SPRMs that mediate subsets of agonist and/or
      antagonist activities, and discuss the clinical potential of these compounds.

PMID- 15714387
TI  - Revealing progesterone's role in uterine and mammary gland biology: insights from
      the mouse.
AB  - Apart from distinguishing the in vivo effects of progesterone (P) from those of
      estrogen (E), the progesterone receptor knockout (PRKO) mouse has furnished
      unprecedented access to novel cell-signaling paradigms, hitherto unsuspected.
      Along with providing new cellular principles by which P influences proliferative
      and differentiative programs obligate for tissue development and tumor
      progression, the PRKO in conjunction with transcript profiling has begun to
      uncover the transcriptional cascades underlying these processes. Moreover,
      studies on isoform-specific knockouts for PR-A (PR-AKO) and PR-B (PR-BKO) have
      clearly defined distinct physiological roles for the two subtypes of PR,
      providing essential physiological support for previous in vitro observations.
      Although the PR-AKO exhibits an infertility phenotype, the PR-BKO displays normal
      fecundity. Conversely, although normal mammary morphogenesis can manifest in the
      PR-AKO, pregnancy-associated mammary morphogenesis is severely impaired in the PR
      BKO. By virtue of its ability to suppress E-induced and PR-B-mediated uterine and
      mammary proliferation, the PR-A isoform is likely to be an attractive drug target
      for the next generation of selective PR modulators in the treatment of uterine
      and mammary gland hyperplasia. Along with defining the dynamic interplay between
      E and P responses and physiological events mediated by PR-A and PR-B, further
      studies on these models should provide a broader conceptual framework for
      understanding abnormal progestin responses in vivo, with attendant implications
      for the management of female reproductive health and for the diagnosis and/or
      treatment of breast cancer.

PMID- 15714388
TI  - Use of the progesterone receptor antagonist RU 486 to identify novel progesterone
      receptor-regulated pathways in implantation.
AB  - The steroid hormone progesterone (P) is a critical regulator of embryo
      implantation and maintenance of pregnancy. P acting through the nuclear
      progesterone receptors (PRs) regulates the expression of specific gene networks
      that in turn control the extensive cell proliferation, differentiation, and
      remodeling that occur in various uterine cell types during the progressive phases
      of implantation. To identify the P-regulated pathways that underlie the
      implantation process in the mouse, we employed RU 486, a well-characterized PR
      antagonist that binds to the receptor and blocks its gene regulatory function. We
      performed messenger RNA (mRNA) profiling in the peri-implantation uterus using
      oligonucleotide microarrays to analyze changes in mRNA levels in response to RU
      486. This analysis provided, for the first time, a comprehensive profile of PR
      regulated gene networks with potential roles during implantation. Our study
      identified a variety of novel PR-regulated molecules, such as growth factors,
      protease inhibitors, metabolic enzymes, peptide hormones, transcription factors,
      immune response molecules, cytoskeletal proteins, and cell adhesion molecules,
      that are potential mediators of P action in the peri-implantation mouse uterus.
      This article provides a brief description of the expression and function of these
      newly identified molecular pathways.

PMID- 15714389
TI  - Nonsteroidal progesterone receptor modulators: structure activity relationships.
AB  - Progesterone, acting primarily via the progesterone receptor (PR), plays an
      essential role in the regulation of female reproduction. Steroidal progestins
      (i.e., PR agonists) are commonly used in women's health, such as in contraception
      and hormone therapy and for the treatment of gynecological disorders. Recent
      studies in women and in nonhuman primates also indicate that PR antagonists may
      have potential applications in contraception and for the treatment of
      reproductive disorders such as fibroids and endometriosis. Currently, all
      clinically available PR agonists and antagonists are steroidal compounds. They
      often cause various side effects due to their functional interactions with other
      steroid receptors or because of effects associated with their steroidal
      metabolites. In an effort to identify more receptor-selective and structurally
      diverse compounds that may render clinical advantages over steroidal PR ligands,
      numerous receptor-selective novel nonsteroidal PR agonists and antagonists have
      been discovered. This review focuses on the structure activity relationships and
      the biological profile of the nonsteroidal PR modulators discovered in the last
      decade.

PMID- 15714390
TI  - Discovery, chemistry, and reproductive pharmacology of asoprisnil and related
      11beta-benzaldoxime substituted selective progesterone receptor modulators
      (SPRMs).
AB  - Asoprisnil (J 867; benzaldehyde, 4-[(11beta, 17beta)-17-methoxy-17
      (methoxymethyl)-3-oxoestra-4, 9-dien-11beta-yl]-, 1-oxime) is the prototype of a
      novel class 11beta-benzaldoxime-substituted selective progesterone receptor
      modulators (SPRMs) and the first-in-class SPRM to reach an advanced stage of
      clinical development for the treatment of uterine fibroids and endometriosis.
      This compound was selected in a drug discovery program aimed to identify
      progesterone receptor (PR) ligands with predominant agonist but also some
      antagonist activities. The screening program included a range of receptor binding
      studies and a hierarchy of in vivo tests. A series of 11beta-benzaldoxime
      substituted steroidal compounds exhibiting mixed PR agonist/antagonist effects
      were synthesized and characterized. For inclusion in this class of compounds, two
      methods of synthesis were developed and optimized. The 11beta-benzaldoxime
      substituted SPRMs showed high PR binding affinities, reduced glucocorticoid
      receptor affinities compared with the antiprogestin mifepristone, marginal
      androgen receptor binding affinities, and no binding to estrogen receptors.
      Animal tests in guinea pigs (luteolysis inhibition assay) and rabbits (McPhail
      test) constituted the secondary screening tests. A mosaic of progesterone agonist
      and antagonist effects were found in various models. The most agonistic compounds
      were selected for further evaluation in animal models with respect to labor
      induction and endometrial effects. Unlike progesterone antagonists, asoprisnil
      and related compounds showed marginal effects on labor and parturition in guinea
      pigs. Proof-of-concept studies in nonhuman primates revealed endometrial
      antiproliferative effects of selected compounds, including asoprisnil and J 1042,
      in the presence of amenorrhea and follicular phase estradiol concentrations.
      Asoprisnil was selected for further clinical development. It shows promising
      results in the treatment of uterine leiomyomata and endometriosis.

PMID- 15714391
TI  - Progesterone receptor antagonists and the endometrial antiproliferative effect.
AB  - Progesterone receptors (PR) mediate multiple aspects of female reproduction and
      are important targets for reagents that can modulate progesterone-dependent
      events. Many such reagents have been developed, and they range from full PR
      antagonists (PAs) to compounds with mixed agonist/antagonist actions, currently
      known as selective progesterone receptor modulators (SPRMs). In women and
      nonhuman primates, many PR antagonists suppress estrogen-dependent mitotic
      activity in the endometrial glands as well as block progestational development of
      the endometrium. These latter effects are tissue- and species-specific, are most
      dramatic in women and nonhuman primates, and are referred to as endometrial
      antiproliferative effects. Recent evidence suggests that the endometrial androgen
      receptor plays an important role in these effects. For example, endometrial
      androgen receptors are increased by treatment with PAs, and combination treatment
      with estrogen, a PA, and an antiandrogen (flutamide) prevents the endometrial
      antiproliferative effect. Various PR modulators have great promise as
      gynecological therapeutics, but additional research is needed to improve our
      understanding of their endometrial effects.

PMID- 15714392
TI  - Mifepristone in abortion care.
AB  - With the addition of a prostaglandin analog, mifepristone allows for successful
      outpatient termination of pregnancy up to 63 days gestation in 92-99% of women.
      In the inpatient setting, studies have shown that mifepristone in combination
      with a prostaglandin analog is also effective as an abortifacient in the late
      first trimester. In the second trimester, the addition of mifepristone to a
      prostaglandin regimen has been shown to expedite induction time. At all stages of
      pregnancy, the use of mifepristone facilitates and ameliorates prostaglandins'
      expulsive effects on the uterine contents. The rich literature regarding
      mifepristone in the setting of abortion care has made an important contribution
      to how physicians treat undesired and problem pregnancies. As with any area of
      medicine, treatment options provide important flexibility for patients and
      clinicians alike.

PMID- 15714393
TI  - Antiprogestins for contraception?
AB  - Antiprogestins could be a very promising group of compounds for contraception
      because they counteract the effects of progesterone, a key hormone for normal
      reproductive functioning. Great efforts have therefore been devoted to testing
      various ways of using these compounds for family planning. Most of this work has
      involved mifepristone; other antiprogestins have not been available for trials.
      With a few exceptions, the outcome of the studies performed to date has not met
      expectations. The most promising approaches seem to be the use of antiprogestins
      for emergency contraception, perhaps also as a daily pill when the dose is high
      enough to block ovulation, and in sequential regimens followed by a progestin.
      Given that antiprogestins differ in their affinity for target organs, better
      results could possibly be achieved by using more specific compounds than
      mifepristone. It is hoped that a wider choice of antiprogestational compounds
      will soon become available for research.

PMID- 15714394
TI  - ORG 33628 and ORG 31710 to control vaginal bleeding in progestin-only
      contraceptive regimens.
AB  - ORG 31710 and ORG 33628 were used in studies aiming to control vaginal bleeding
      in combination with progestagen-only contraception in primates. Preclinical
      evidence in monkeys with ORG 31710 has shown that a monthly supplementary
      administration to a progestagen-only contraceptive improves cycle control,
      probably as a result of a local endometrial effect (i.e., blocking of the
      progesterone receptor). In clinical trials ORG 31710 appeared to be effective for
      inducing vaginal bleeding after single-dose administration in the luteal phase of
      a normal cycle and for improving vaginal bleeding patterns of subjects using the
      75 microg desogestrel progestagen-only pill (POP). Under POP treatment, ORG 31710
      induced monthly bleeding and completely reduced intermittent (or breakthrough)
      bleedings, albeit for a limited number of days (+/- 10 days); thereafter, the
      incidence of spot bleedings returned to average levels with a POP, until the next
      monthly ORG 31710 administration. The temporary character of the effect was not
      predicted on the basis of the monkey studies, in which the improved bleeding
      pattern lasted a full cycle. Similar clinical results have been obtained with ORG
      33628 both as administered in the luteal phase of the normal cycle and as given
      once (and twice) every 28 days in combination with the 75 microg desogestrel POP.
      Again, the improvement of the (POP-) bleeding pattern was not considered
      effective enough. In another approach, a continuous combined (daily) treatment of
      a progestagen (desogestrel) and the compound ORG 33628 was evaluated. It was
      hypothesized that if properly balanced, the progestagen would provide sustained
      ovulation inhibition, while the antagonistic activity of ORG 33628 would provide
      prevention of intermittent vaginal bleedings without antagonizing the inhibition
      of ovulation. This hypothesis is supported by the observation (from previous
      studies) that the antagonistic activity is higher at the level of the endometrium
      than at the level of the hypothalamus/pituitary. The continuous combined concept
      was studied in a single-center, double-blind, randomized trial of ORG 33628 at
      three different dosages in combination with the 75 microg desogestrel POP
      administered to healthy female volunteers. Effects on vaginal bleeding,
      endometrium, and ovarian function were evaluated. Vaginal bleeding was reduced
      with increasing doses of ORG 33628, but the inhibition of ovulation appeared to
      be compromised at the same time. In summary, the available studies suggest that
      there may be a progestagen/progesterone receptor-antagonist combination that
      provides the desired cycle control without compromising the inhibition of
      ovulation, but the ideal regimen or ratio has yet to be found.

PMID- 15714395
TI  - [A fly in the ointment?].

PMID- 15714396
TI  - [The present role of interventional lung assist (ILA) in critical care medicine].
AB  - The development of low resistance oxygenators widens the therapeutic options for
      patients with acute respiratory failure (ARDS). Pumpless arteriovenous
      interventional lung assist systems (ILA) can be used in a subgroup of patients
      with ARDS. ILA might be indicated in earlier stages of ARDS following a
      multimodal treatment approach.

PMID- 15714397
TI  - [Guidelines for preventing health-care-associated pneumonia].
AB  - Because of the high morbidity and mortality associated with health-care
      associated pneumonia, it is important to implement evidence-based prevention
      measures. Recently by CDC published Guidelines for Preventing Health-Care
      Associated Pneumonia describe prevention measures based on evaluated studies,
      randomized controlled trials or meta-analyses. In this paper the most important
      prevention measures are given, as well as the evidence classification. "Among the
      changes in the recommendations to prevent bacterial pneumonia, especially
      ventilator-associated pneumonia, are the preferential use of or tracheal rather
      than naso-tracheal tubes in patients who receive mechanically assisted
      ventilation, the use of noninvasive ventilation to reduce the need for and
      duration of endotracheal intubation, changing the breathing circuits of
      ventilators when they malfunction or are visibly contaminated, and (when
      feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage
      of respiratory secretions."

PMID- 15714398
TI  - [Microbiological diagnostic and antibiotic management of community aquired and
      nosocomial pneumonias in intensive care units in Germany].

PMID- 15714399
TI  - [Extravasal position of central venous catheters despite unsuspicious ECG
      guidance].
AB  - OBJECTIVE: Does the electrocardiographic method for central venous catheter
      positioning distinguish between a correct intravasal and a malpositioned
      extravasal position? METHODS: 24 cardiac surgical patients were enrolled in this
      prospective observational study. In 18 patients the left, in another 6 patients
      the right internal jugular vein was cannulated. Using a J-wire within a triple
      lumen catheter the amplitude of the P-wave was measured at 3 different intravasal
      sites: Intra-1: (intravasal baseline electrocardiogram), i. e. 10 cm marking of
      the catheter on skin level; Intra-2: clear rise of the P-wave amplitude upon
      further insertion of the catheter; Intra-3: maximum P-wave amplitude. At this
      position the control of the catheter tip was achieved by means of
      transoesophageal echocardiography (TOE). Intraoperatively, another J-wire within
      a triple-lumen catheter was placed by the heart surgeon on 3 extravasal sites and
      the ECG was recorded: Extra-1: extravasal at the left innominate vein above the
      pericardial reflection; Extra-2: extravasal on the superior vena cava below the
      pericardial reflection; Extra-A: extravasal on ascending aorta below the
      pericardial reflection. The catheter was suture fixed with its tip in position
      Intra-3. Post surgery a chest radiograph was taken. RESULTS: All catheter tips
      were visualised at the basis of the Crista terminals (border between right atrium
      and superior vena cava) by TOE control. The rise of the P wave amplitude at Intra
      2, Extra-2 and Extra-A was highly significant compared to the base line at Intra
      1 (Intra-1/Intra-2, Intra-1/Extra-2, Intra-1/Extra-A: p in each case < 0.001).
      The P wave amplitudes of the corresponding intra- and extravasal positions of the
      left innominate vein (Intra-1/Extra-1, n = 18, p = 0.096)) as well as those of
      the superior vena cava (Intra-2/Extra-2, n = 24, p = 0.859) did not differ.
      CONCLUSION: The electrocardiographic method can not differentiate between intra-
      and extravasal position of a central venous catheter, and thus, presumably fails
      to identify malpositioning as a result of vascular perforation.

PMID- 15714400
TI  - [Procalcitonin as a marker for severe sepsis in an immunosuppressed patient].
AB  - A 22 year old female was admitted to the emergency department with high fever up
      to 41,5 degrees C, tachycardia, and arterial hypotension. Clinically, she
      presented with bilateral pulmonary coarse crackles. Diagnosis on admission was
      pneumonia with septic shock. Intriguingly, procalcitonin (PCT) was increased
      early, reaching up to 435 ng/mL, while C-reactive protein levels were only
      moderately increased, with several days delay. The sepsis was originated from a
      multi-resistant pseudomonas aeruginosa pneumonia. Remarkably, the course of PCT
      levels reflected the severity of septic shock in that it paralleled noradrenaline
      demand. Ten months previously, the patient had been diagnosed with acute
      disseminated brainstem encephalitis (ADEM), and had received two cycles of
      intravenous cyclophosphamide. Our case illustrates that PCT is an early marker
      for sepsis and it indicates that PCT may also be a valuable marker for the
      severity of sepsis in immunosuppressed patients.

PMID- 15714401
TI  - [Feasible central and peripherous invasive methods of stimulation in the
      treatment of pain].

PMID- 15714404
TI  - Genomewide significant linkage to stuttering on chromosome 12.
AB  - Stuttering is a common and sometimes severe communication disorder, of unknown
      primary etiology, that exists in populations worldwide. Many types of evidence
      suggest a genetic contribution to stuttering; however, the complex inheritance of
      this disorder has hindered identification of these factors. We have employed
      highly inbred families to increase the power of linkage analysis of this
      disorder. Forty-four Pakistani families with documented or probable
      consanguinity, from the city of Lahore and surrounding areas, were included. Each
      family contained multiple cases of stuttering, which were diagnosed using the
      Stuttering Severity Instrument. Using the Marshfield Weber 9 marker panel, we
      performed a genomewide linkage scan focused on affected individuals and their
      parents. The analysis included 199 genotyped individuals, 144 affected and 55
      unaffected. The Pedigree Relationship Statistical Test (PREST) was used to
      identify pedigrees that required additional specification of inbreeding. Initial
      nonparametric analysis gave evidence of linkage on chromosomes 1, 5, 7, and 12.
      Additional genotyping was performed on chromosome 12 to a 5-cM level of
      resolution, and 16 additional individuals were then included, bringing the number
      of families to 46. Analysis of the enlarged data set provided consistent evidence
      of linkage on chromosome 12: the S(homoz) scoring function gave a nonparametric
      LOD score of 4.61, and a LOD score of 3.51 was obtained using the S(all) scoring
      function. These results suggest that a locus on chromosome 12q may contain a gene
      with a large effect in this sample.

PMID- 15714405
TI  - Rapid and fatal meningococcal disease due to a strain of Neisseria meningitidis
      containing the capsule null locus.
AB  - BACKGROUND: Neisseria meningitidis continues to be an important cause of invasive
      bacterial disease among children and young adults worldwide. In Canada, N.
      meningitidis strains that bear serogroups B and C polysaccharide capsules
      predominate. We report the first documented case of invasive meningococcal
      disease in an immunocompetent host caused by an acapsular strain of N.
      meningitidis containing the capsule null locus (cnl). METHODS: Analysis of the
      isolate was performed with use of serological and molecular methods, including
      multilocus sequence typing and cnl gene identification. Analysis of 16S ribosomal
      RNA (rRNA) and porA genes was also performed to confirm the identity of the
      bacterium. RESULTS: The patient was a healthy, immunocompetent 13-year-old child,
      and N. meningitidis was recovered from a sample of her cerebrospinal fluid before
      death. The isolate was nontypeable by both conventional antisera and indirect
      whole-cell enzyme-linked immuosorbent assay methods using antibodies to
      serogroups B, C, Y, and W135. The isolate was further identified as a cnl strain,
      serotype 15 (ST-198). N. meningitidis-specific DNA was identified in the isolate
      and in the pre- and postmortem specimens by 16S rRNA and porA gene analysis.
      CONCLUSIONS: This is the first reported case of fatal meningococcal disease
      caused by an acapsular cnl strain of N. meningitidis that was isolated from an
      immunocompetent host. Routine molecular diagnostic methods targeted at the cnl
      locus failed to detect this organism, indicating a need to determine the
      incidence of infection with cnl strains among patients with culture-negative
      invasive disease.

PMID- 15714406
TI  - Cat-scratch disease (ocular bartonellosis) presenting as bilateral recurrent
      iridocyclitis.
AB  - An otherwise healthy 9-year-old girl presented with bilateral recurrent anterior
      uveitis. Thirteen months later, the diagnosis of cat-scratch disease (ocular
      bartonellosis) was suspected when neuroretinitis appeared. Confirmation was based
      on serological test results positive for Bartonella henselae. Antibiotic
      treatment completely cured the disease, and there have been no further
      manifestations during a follow-up period of 6 years.

PMID- 15714407
TI  - Candida glabrata endophthalmitis treated successfully with caspofungin.
AB  - A 39-year-old man with Candida glabrata endophthalmitis was successfully treated
      with a 28-day course of intravenous caspofungin. Presence of underlying renal
      insufficiency and infection with a drug-resistant strain precluded use of
      amphotericin B or fluconazole. Intravitreal administration of antifungals and
      vitrectomy were not required. The role of caspofungin in Candida endophthalmitis
      is discussed.

PMID- 15714408
TI  - Infectious Diseases Society of America guidelines for the diagnosis and treatment
      of asymptomatic bacteriuria in adults.

PMID- 15714409
TI  - Quantitative histological examination of mechanical heart valves.
AB  - BACKGROUND: Histological demonstration of microorganisms, vegetations, or active
      endocarditis in cardiac valve tissue is included in the Duke criteria and is
      considered to be a criterion of confirmed infective endocarditis. However, the
      histological features that characterize infective endocarditis are not accurately
      defined at the qualitative and quantitative levels. METHODS: Pathologic analysis
      of tissue adjoining mechanical cardiac valves was undertaken retrospectively for
      21 patients who underwent surgical removal of a mechanical valve because of
      suspected infective endocarditis and 69 patients who underwent surgical removal
      of a mechanical valve because of noninfectious dysfunction. To better define the
      histological criteria for infective endocarditis, we used quantitative image
      analysis to compare these 2 groups of patients with respect to valvular fibrosis,
      calcifications, vegetations, patterns of inflammation, and vascularization.
      RESULTS: Histologically, infective endocarditis in patients with mechanical
      valves was characterized by the demonstration of microorganisms, vegetations, and
      significant neutrophil-rich inflammatory infiltrates with extensive
      neovascularization. In contrast, valve tissue specimens from patients with
      mechanical valves that were removed because of noninfectious complications showed
      significant rates of extensive fibrosis and, when present, inflammatory
      infiltrates that were mainly composed of macrophages and lymphocytes. A
      neutrophil surface area with a cutoff value of > or =2% of the total valve tissue
      surface is highly predictive of (90%) and specific for (98%) infective
      endocarditis. CONCLUSIONS: When no microorganisms are detected and vegetations
      are lacking in tissue adjacent to a mechanical valve, neutrophil-rich
      inflammation and extensive neovascularization might better histologically define
      the term "active endocarditis" in the Duke criteria. This definition would allow
      differentiation between infective endocarditis and inflammatory noninfectious
      valve processes in patients with mechanical cardiac valves.

PMID- 15714410
TI  - Frequent detection of respiratory viruses in adult recipients of stem cell
      transplants with the use of real-time polymerase chain reaction, compared with
      viral culture.
AB  - BACKGROUND: Respiratory virus infections have been recognized as important causes
      of severe pneumonia in patients who have undergone stem cell transplantation
      (SCT). Reported incidences of respiratory virus infection in adult SCT recipients
      vary in the literature from 3.5% to 36% when determined by viral culture.
      However, a more sensitive method to assess the presence of respiratory viruses in
      the lower airways may be important for delineation of the true incidence of
      respiratory virus-associated pneumonia and may be essential for guidance on
      implementation of antiviral therapy and prevention or limitation of nosocomial
      spread of infection with respiratory viruses. METHODS: To determine the incidence
      and severity of respiratory tract illness (RTI) and to assess the diagnostic
      value of real-time reverse-transcriptase polymerase chain reaction (RT-PCR)
      versus viral culture, 72 SCT recipients were monitored during a 6-month period.
      RESULTS: A respiratory virus was detected in 21% of episodes of RTI by viral
      culture and in 63% of RTI episodes by real-time RT-PCR (P<.0001). In lower
      respiratory tract illness, real-time RT-PCR was much more sensitive than viral
      culture for detection of respiratory virus (73% vs. 9%; P=.008). The mortality
      rate for patients with respiratory virus-associated lower respiratory tract
      illness (25%) was similar to rates reported elsewhere. Respiratory viruses
      (predominantly rhinovirus) were detected by real-time RT-PCR in 9% of samples
      obtained from symptom-free SCT recipients at predetermined times by real-time RT
      PCR and by viral culture in 1% (P<.0001), indicating that asymptomatic shedding
      of respiratory viruses also occurs. CONCLUSION: We conclude that, although
      asymptomatic shedding of respiratory virus occurs, respiratory viruses are
      frequent causes of RTI in SCT recipients.

PMID- 15714411
TI  - Short-course therapy with rifampin plus isoniazid, compared with standard therapy
      with isoniazid, for latent tuberculosis infection: a meta-analysis.
AB  - BACKGROUND: A major difficulty associated with the use of standard therapy with
      isoniazid for latent tuberculosis infection is poor patient adherence to therapy
      because of the prolonged course required. Shorter courses of therapy involving >
      or =2 drugs have been proposed as an alternative to standard therapy, but they
      have not undergone enough testing. METHODS: We performed a meta-analysis to
      determine the equivalence of daily short-course therapy with rifampin plus
      isoniazid for 3 months and standard therapy with isoniazid for 6-12 months. The
      end points that were evaluated were development of active tuberculosis, severe
      adverse drug reactions, and death. We searched published information in the
      Cochrane Library, MEDLINE, and Embase databases, as well as unpublished
      information in the Cambridge Scientific Abstracts Internet database, Conference
      Papers Index, AIDS and Cancer Research Abstracts, and ClinicalTrials.gov. We also
      scanned the reference lists of articles. We only included trials in which
      individuals were randomly allocated to receive treatment. Two reviewers
      independently applied the criteria for trial selection, assessed trial quality,
      and extracted data. RESULTS: Five trials comprising 1926 adults from Hong Kong,
      Spain, and Uganda were identified. The mean duration of follow-up varied from 13
      to 37 months. Overall, development of active tuberculosis was equivalent in
      association with both regimens (pooled risk difference, 0%; 95% confidence
      interval [CI], -1% to 2%; percentage of total variation across the studies that
      is the result of heterogeneity rather than chance [I2], 0%; P=.86). Severe
      adverse effects were reported with a similar frequency for both regimens (pooled
      risk difference, -1%; 95% CI, -7% to 5%) but with statistically significant
      heterogeneity detected (I2, 78%; P=.001). However, a subanalysis of high-quality
      trials (including 74% of the sample size) suggested that both regimens were
      equally safe. In 3 trials (comprising 1390 patients) that provided data on
      mortality, the regimens showed equivalence (pooled risk difference, -1%; 95% CI, 
      4% to 2%; I2, 2.7%; P=.38). CONCLUSION: Short-course therapy with rifampin plus
      isoniazid was equivalent to standard therapy with isoniazid in terms of efficacy,
      the proportion of severe side effects that occurred, and mortality.

PMID- 15714412
TI  - Outbreak of listeriosis among Mexican immigrants as a result of consumption of
      illicitly produced Mexican-style cheese.
AB  - BACKGROUND: In 2000, an outbreak of listeriosis among Hispanic persons was
      identified in Winston-Salem, North Carolina. The objectives of the present study
      were to identify the source of, strains associated with, and risk factors for
      Listeria monocytogenes infection for patients affected by the outbreak. METHODS:
      Microbiological, case-control, and environmental investigations were conducted.
      Participants in the case-control study were case patients who became infected
      with L. monocytogenes between 1 October 2000 and 31 January 2001 and control
      subjects who were matched with case patients on the basis of ethnicity, sex, age,
      and pregnancy status. All participants were residents of Winston-Salem. RESULTS:
      We identified 13 patients, all of whom were Hispanic, including 12 females who
      were 18-38 years of age. Eleven case patients were pregnant; infection with L.
      monocytogenes resulted in 5 stillbirths, 3 premature deliveries, and 3 infected
      newborns. Case patients were more likely than control subjects to have eaten the
      following foods: fresh, unlabeled, Mexican-style cheese sold by door-to-door
      vendors (matched odds ratio [MOR], 17.5; 95% confidence interval [CI], 2.0
      152.5); queso fresco, a Mexican-style soft cheese (MOR, 7.3; 95% CI, 1.4-37.5);
      and hot dogs (MOR, 4.6; 95% CI, 1.1-19.4). L. monocytogenes isolates recovered
      from 10 female case patients, from cheese bought from a door-to-door vendor, from
      unlabeled cheese from 2 Hispanic markets, and from raw milk from a local dairy
      had indistinguishable patterns on pulsed-field gel electrophoresis. CONCLUSIONS:
      This outbreak of listeriosis was caused by noncommercial, fresh, Mexican-style
      cheese made from contaminated raw milk traced to 1 local dairy. We recommend
      educating Hispanic women about food safety while they are pregnant, enforcing
      laws that regulate the sale of raw milk and dairy products made by unlicensed
      manufacturers, making listeriosis a reportable disease in all states, routinely
      interviewing case patients, and routinely subtyping clinical L. monocytogenes
      isolates.

PMID- 15714413
TI  - Cytomegalovirus infection of the heart is common in patients with fatal
      myocarditis.
AB  - BACKGROUND: Although enteroviruses and adenoviruses are considered to be the
      leading causes of the usually mild clinical myocarditis, little is known about
      the etiology of severe or fatal myocarditis. METHODS: We collected all available
      clinical records and myocardial autopsy samples for patients who had myocarditis
      recorded as the underlying cause of death in Finland during the period of 1970
      1998. Findings for all available patients (20 men and 20 women; median age, 49
      years) with myocarditis that fulfilled the Dallas criteria and who had sufficient
      data were included in the study. Twelve subjects who had died accidentally served
      as control subjects. Polymerase chain reaction (PCR) and in situ hybridization
      assays were used for detection of viral genomes (adenovirus, cytomegalovirus,
      enterovirus, human herpesvirus 6, influenza A and B viruses, parvovirus B19, and
      rhinovirus) in heart samples. RESULTS: Viral nucleic acids were found in the
      hearts of 17 patients (43%), including cytomegalovirus (15 patients), parvovirus
      B19 (4 patients), enterovirus (1 patient), and human herpesvirus 6 (1 patient).
      In 4 patients, cytomegalovirus DNA was found in addition to parvovirus B19 or
      enterovirus genomes. No adenoviruses, rhinoviruses, or influenza viruses were
      detected in this study of fatal myocarditis. In 67% of the patients for whom PCR
      was positive for cytomegalovirus, in situ hybridization revealed viral DNA in
      cardiomyocytes. Only 1 of these patients was immunocompromised. In the control
      group, only human herpesvirus 6 (1 subject) and parvovirus B19 (1 subject) DNA
      were detected. CONCLUSIONS: In this population-based study, cytomegalovirus was
      found to be the most common specific finding in immunocompetent patients with
      fatal myocarditis. This may have important clinical implications for the
      treatment of severe acute myocarditis.

PMID- 15714414
TI  - Evaluation of human-to-human transmission of monkeypox from infected patients to
      health care workers.
AB  - BACKGROUND: In 2003, human monkeypox was first identified in the United States.
      The outbreak was associated with exposure to infected prairie dogs, but the
      potential for person-to-person transmission was a concern. This study examines
      health care worker (HCW) exposure to 3 patients with confirmed monkeypox.
      METHODS: Exposed HCWs, defined as HCWs who entered a 2-m radius surrounding case
      patients with confirmed monkeypox, were identified by infection-control
      practitioners. A self-administered questionnaire and analysis of paired serum
      specimens determined exposure status, immune response, and postexposure signs and
      symptoms of monkeypox. RESULTS: Of 81 exposed HCWs, 57 (70%) participated in the
      study. Among 57 participants, 40 (70%) had > or =1 unprotected exposure; none
      reported signs or symptoms consistent with monkeypox illness. One exposed HCW
      (2%), who had been vaccinated for smallpox within the past year, had serological
      evidence of recent orthopoxvirus infection; acute- and convalescent-phase serum
      specimens tested positive for anti-orthopoxvirus IgM. No exposed HCWs had signs
      and symptoms consistent with monkeypox. CONCLUSION: More than three-quarters of
      exposed HCWs reported at least 1 unprotected encounter with a patient who had
      monkeypox. One asymptomatic HCW showed laboratory evidence of recent
      orthopoxvirus infection, which was possibly attributable to either recent
      infection or smallpox vaccination. Transmission of monkeypox likely is a rare
      event in the health care setting.

PMID- 15714415
TI  - Risk factors for hematogenous complications of intravascular catheter-associated
      Staphylococcus aureus bacteremia.
AB  - BACKGROUND: The role of both host and pathogen characteristics in hematogenous
      seeding following Staphylococcus aureus bacteremia is incompletely understood.
      METHODS: Consecutive patients with intravascular catheter-associated
      Staphylococcus aureus bacteremia were prospectively recruited over a 91-month
      period. The corresponding bloodstream isolates were examined for the presence of
      35 putative virulence determinants. Patient and bacterial characteristics
      associated with the development of hematogenous complications (HCs) (i.e., septic
      arthritis, vertebral osteomyelitis, or endocarditis) were defined. RESULTS: HC
      occurred in 42 (13%) of 324 patients. Patient characteristics at diagnosis that
      were associated with HC included community onset (relative risk [RR], 2.25; 95%
      confidence interval [CI], 1.24-4.07; P=.007), increased symptom duration (odds
      ratio for each day, 1.14; 95% CI, 1.06-1.2; P<.001), presence of a long-term
      intravascular catheter or noncatheter prosthesis (RR, 4.02; 95% CI, 1.74-9.27;
      P<.001), hemodialysis dependence (RR, 3.84; 95% CI, 2.08-7.10; P<.001), and
      higher APACHE II score (P=.02). Bacterial characteristics included sea (RR, 2.03;
      95% CI, 1.16-3.55; P=.011) and methicillin-resistant S. aureus (MRSA) (RR, 2.09;
      95% CI, 1.19-3.67; P=.015). Subsequent failure to remove a catheter was also
      associated with HC (RR, 2.28; 95% CI, 1.22-4.27; P=.011). On multivariable
      analysis, symptom duration, hemodialysis dependence, presence of a long-term
      intravascular catheter or a noncatheter device, and infection with MRSA remained
      significantly associated with HC. CONCLUSIONS: This investigation identifies 4
      host- and pathogen-related risk factors for hematogenous bacterial seeding and
      reaffirms the importance of prompt catheter removal.

PMID- 15714416
TI  - Late-onset cytomegalovirus disease as a significant complication in solid organ
      transplant recipients receiving antiviral prophylaxis: a call to heed the
      mounting evidence.

PMID- 15714417
TI  - Counterpoint: prevention of cytomegalovirus (CMV) infection and CMV disease in
      recipients of solid organ transplants: the case for prophylaxis.

PMID- 15714418
TI  - Economic access to effective drugs for falciparum malaria.
AB  - The increasing death toll from drug-resistant falciparum malaria is cause for
      international concern. In 2002, the US Agency for International Development
      commissioned the Institute of Medicine (IOM) to recommend global actions to
      ensure the broadest possible access to new, effective antimalarial treatments. In
      a report issued in 2004, the IOM Committee on Economics of Antimalarial Drugs
      recommended a global subsidy of 300 million dollars to 500 million dollars per
      year to replace increasingly ineffective drugs with coformulated artemisinin
      combination treatments to be distributed through public and private channels in
      affected areas. This approach allows the existing market to support the switch to
      new drugs and keeps treatment costs for consumers at levels similar to the
      current price of chloroquine. The leverage of an international subsidy of
      combination therapy can also discourage the distribution of monotherapies (such
      as solo artemisinins), the use of which might foster increasing resistance to
      antimalarial drugs in the future.

PMID- 15714419
TI  - Insights into severe sepsis in older patients: from epidemiology to evidence
      based management.
AB  - Up to 60% of patients who develop severe sepsis in the United States are > or =65
      years of age, and the incidence of sepsis in this population is steadily
      increasing. Elderly individuals have an increased risk of developing sepsis,
      compared with younger patients, because of frequent comorbidities,
      institutionalization, declining performance status, and altered immune function.
      The clinical presentation of older patients with sepsis is often atypical,
      leading to a difficult and delayed diagnosis. Although increasing age appears to
      confer a high risk of death due to severe sepsis, recent evidence shows that many
      older patients respond well to selected interventions when the interventions are
      initiated in a timely fashion. Newly published clinical practice guidelines
      outline key recommendations regarding the treatment of patients with severe
      sepsis. Clinicians must be aware of the level of evidence in support of various
      interventions and must keenly screen older survivors for ongoing deficits that
      will limit their functional recovery.

PMID- 15714420
TI  - Development of HIV with drug resistance after CD4 cell count-guided structured
      treatment interruptions in patients treated with highly active antiretroviral
      therapy after dual-nucleoside analogue treatment.
AB  - BACKGROUND: For patients with human immunodeficiency virus (HIV) infection,
      structured treatment interruption (STI) is an attractive alternative strategy to
      continuous treatment, particularly in resource-restrained settings, because it
      reduces both side effects and costs. One major concern, however, is the
      development of resistance to antiretroviral drugs that can occur during multiple
      cycles of starting and stopping therapy. METHODS: HIV genotypic drug resistance
      was investigated in 20 HIV-infected Thai patients treated with highly active
      antiretroviral therapy (HAART) and CD4 cell count-guided STI after dual
      nucleoside reverse-transcriptase inhibitor (NRTI) treatment. Resistance was
      tested at the time of the switch from dual-NRTI treatment to HAART and when HAART
      was stopped during the last interruption. RESULTS: After STI, one major drug
      resistance mutation occurred (T215Y), and, in the 4 samples with preexisting
      major mutations (D67N [n=2], K70R [n=2], T215Y [n=2], and T215I [n=1]), the
      mutations disappeared. All mutations in the HIV protease gene were minor
      mutations already present, in most cases, before STI was started, and their
      frequency was not increased through STI, whereas the frequency of reverse
      transcriptase gene mutations significantly decreased after the interruptions.
      After the 48-week study period, no patients had virological failure. Long-term
      follow-up (108 weeks) showed 1 case of virological failure in the STI arm and 1
      in the continuous arm. No virological failure was seen in patients with major
      mutations. CONCLUSIONS: Major HIV drug-resistance mutations were not induced
      through CD4 cell count-guided treatment interruptions in HIV-infected patients
      successfully treated with HAART after dual-NRTI therapy.

PMID- 15714421
TI  - CD4 cell count-guided treatment interruption: be smart and wait for more
      evidence.

PMID- 15714422
TI  - Prognostic significance of JC virus DNA levels in cerebrospinal fluid of patients
      with HIV-associated progressive multifocal leukoencephalopathy.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) remains a frequent
      and life-threatening complication of human immunodeficiency virus (HIV) infection
      in the era of highly active antiretroviral therapy (HAART). Although one-half of
      patients with this disease will survive, the outcome is unpredictable at
      diagnosis, and prognostic markers are needed. METHODS: JC virus (JCV) DNA levels
      were measured in cerebrospinal fluid (CSF) samples obtained from 61 HIV-infected
      patients with PML, including 38 patients who were treated with HAART and 23
      patients who did not receive HAART, with use of real-time polymerase chain
      reaction. The diagnostic reliability of the assay was evaluated by comparing CSF
      findings with histopathological findings in patients with PML or other HIV
      related diseases of the central nervous system. The prognostic value was assessed
      by comparing JCV DNA levels with survival and other patient variables. RESULTS:
      The assay had a diagnostic sensitivity of 76% and specificity of 100%. In the
      first CSF sample obtained after onset of PML symptoms, JCV DNA values ranged from
      undetectable to 7.71 log copies/mL (median, 3.64 log copies/mL). JCV DNA levels
      >3.64 log copies/mL correlated significantly with shorter survival and lower CD4+
      cell counts in patients not receiving HAART. However, neither relationship was
      found in patients who were treated with HAART. The analysis of sequential CSF
      samples obtained from 24 patients demonstrated a marked decrease in JCV DNA
      levels over time in HAART-treated patients showing PML stabilization, but not in
      untreated or HAART-treated patients with progressively fatal disease.
      CONCLUSIONS: Measurement of JCV DNA levels in CSF samples may be a useful
      virological marker for management of PML in patients receiving HAART.

PMID- 15714423
TI  - Improvement in highly active antiretroviral therapy-induced metabolic syndrome by
      treatment with pioglitazone but not with fenofibrate: a 2 x 2 factorial,
      randomized, double-blinded, placebo-controlled trial.
AB  - We designed a 2 x 2 factorial, randomized, double-blinded, placebo-controlled
      trial to evaluate the effects of treatment with pioglitazone and/or fenofibrate
      in patients with highly active antiretroviral therapy (HAART)-induced metabolic
      syndrome. We found that the administration of pioglitazone, but not fenofibrate,
      improved insulin resistance, blood pressure, and lipid profile over a 12-month
      period.

PMID- 15714424
TI  - Occult hepatitis B virus infection in HIV-infected patients with isolated
      antibodies to hepatitis B core antigen: Aquitaine cohort, 2002-2003.
AB  - We prospectively assessed the prevalence of occult hepatitis B virus (HBV)
      infection by investigating HBV replication in 160 human immunodeficiency virus
      (HIV)-infected patients with isolated antibodies to hepatitis B core antigen.
      This prevalence was 0.6% (1 case/160 patients; 95% confidence interval, 0%-3.4%).
      A second serum sample was collected later from 52 of the patients. HBV DNA was
      once again undetectable in all patients, except for the sole patient who had
      previously been found to be HBV DNA positive.

PMID- 15714425
TI  - Paradoxical response to antituberculous therapy in infliximab-treated patients
      with disseminated tuberculosis.
AB  - Six of 284 patients treated with infliximab developed active tuberculosis. Four
      (67%) of these patients had a paradoxical response to antituberculous therapy.
      Physicians should be aware of the increased risk of a paradoxical response in
      this population and should consider the use of corticosteroids when a paradoxical
      reaction is suspected.

PMID- 15714426
TI  - Serotype distribution of invasive group B streptococcal isolates in infants:
      results from a nationwide active laboratory surveillance study over 2 years in
      Germany.
AB  - We report the serotype distribution of invasive group B streptococci (GBS)
      isolated from 296 infants in Germany. Serotype distribution was as follows:
      serotype Ia, 15%; Ib, 5%; II, 5%; III, 65%; IV, 1%; and V, 8%. Analysis of
      serotype according to the source of isolation highlighted the considerable role
      of serotype III in meningitis in early-onset infection (82%) and late-onset
      infection (84%). Use of a trivalent GBS vaccine in Germany could theoretically
      provide protection against 84% and 94% of invasive early-onset and late-onset
      infections, respectively.

PMID- 15714427
TI  - Use of interferon-alpha in patients with West Nile encephalitis: report of 2
      cases.
AB  - We describe 2 patients with West Nile virus (WNV) encephalitis who were treated
      experimentally with interferon (IFN)-alpha. Both patients demonstrated
      substantial improvement in mentation and speech on the second day of experimental
      therapy, and neither required endotracheal intubation or admission to the
      intensive care unit during hospitalization. Moreover, during the 9-month follow
      up period, one patient achieved complete recovery, and the other nearly achieved
      complete resolution of sequelae. To our knowledge, this is the first published
      report of the use of IFN-alpha to treat WNV encephalitis. Clinical trials are
      underway to further define the role of this therapy in persons with WNV
      encephalitis.

PMID- 15714428
TI  - Effect of colonization with methicillin-resistant Staphylococcus aureus on
      subsequent infection.

PMID- 15714431
TI  - Chronic obstructive pulmonary disease, antibiotics, and prediction of bacterial
      infection.

PMID- 15714432
TI  - Breakthrough zygomycosis during empirical voriconazole therapy in febrile
      patients with neutropenia.

PMID- 15714433
TI  - Methodological errors in staphylococcal equivalence study.

PMID- 15714434
TI  - Equivalence between oral and intravenous antibiotics when treating serious
      staphylococcal infections?

PMID- 15714436
TI  - Glutamine supplementation for patients with severe cryptosporidiosis.

PMID- 15714437
TI  - Dengue transmission without involvement of mosquito vector.

PMID- 15714438
TI  - Alternative splicing of MDM2 mRNA in lung carcinomas and lung cell lines.
AB  - The MDM2 gene is overexpressed in several human tumors and its product may be
      processed into various isoforms. Recently, alternative splicing forms of MDM2
      mRNA have been detected in various types of tumors. In this study, lung tissue
      from human non small cell lung cancers was examined for MDM2 mRNA splicing
      variants by nested RT-PCR. Of the 117 lung cancer tissue samples analyzed, a
      total of 31 (26.5%) had splice variants for the MDM2 gene, while 59 (50.4%) had
      undetectable levels of MDM2 transcript. Further analysis indicated that the
      predominant variant for 26 of the 31 samples with alternative MDM2 splicing
      products was MDM2-657, a splice variant lacking exons 3-11. Significant
      associations were found between the frequency of alternative splicing and the
      gender and smoking habits of the patients. Approximately 36% of male patients had
      alternative splicing of MDM2 compared with only 9.5% of female patients (P =
      0.008); 44.2% of the smoker patients had alternative MDM2 splice forms versus
      16.2% of nonsmokers (P = 0.003). Furthermore, most normal lung cell lines
      examined possessed only full-length MDM2 mRNA, while among several lung cancer
      cell lines, only H1355 and CaLu-1 cells lacked alternatively spliced MDM2
      transcripts. When H1355 cells were treated in vitro with the cigarette smoke
      carcinogen benzo[a]pyrene (B[a]P) or the B[a]P metabolite benzo[a]pyrene
      diolepoxide (BPDE), three MDM2 splicing products were detected by nested RT-PCR.
      Finally, with the use of several specific inhibitors, we found that BPDE-induced
      MDM2 mRNA alternative splicing in H1355 cells may occur through the PI3K or MAPK
      pathway. Overall, our results suggest that carcinogens present in cigarette smoke
      increase the risk of alternative MDM2 splicing, which is highly associated with
      lung cancer.

PMID- 15714439
TI  - The vaginal pressure profile.
AB  - AIMS: To describe the vaginal pressure profile in asymptomatic nulliparous women.
      METHODS: Fourteen nulliparous women without symptoms of anal or urinary
      incontinence were studied with vaginal manometry. A rapid pull-through technique
      utilized a four-channel water-perfused catheter on a motor-driven puller to
      create a pressure profile for each subject. The profiles were measured with the
      subject at rest and during a sustained contraction of the levator ani muscle. The
      individual subject's pressure profiles were averaged to create a composite
      profile at rest and during squeeze. RESULTS: The vaginal pressure profile at rest
      and during squeeze contains three pressure zones: proximal, mid, and distal. The
      pressure is highest in the mid pressure zone and was labeled as the vaginal high
      pressure zone. In the vaginal high-pressure zone, the maximum pressure during
      squeeze is significantly higher than the maximum pressure at rest (P < 0.05). The
      length of the high-pressure zone is longer during squeeze as compared to rest (P
      < 0.05). The maximum pressures exhibit circumferential asymmetry with the
      pressures in anterior and posterior directions being significantly higher than
      those in the lateral directions (P < 0.05). CONCLUSIONS: The vaginal pressure
      profile is more complex than previously described. Understanding of the vaginal
      pressure profile is crucial when employing vaginal manometry to assess pelvic
      floor muscle strength or as a surrogate for intra-abdominal pressure.

PMID- 15714440
TI  - Differential accumulation of Lhcb gene products in thylakoid membranes of Zea
      mays plants grown under contrasting light and temperature conditions.
AB  - In higher plants many different genes encode Lhcb proteins that belong to a
      highly conserved protein family. Evolutionary conservation of this genetic
      redundancy suggests that individual gene products play different roles in light
      harvesting and photoprotection depending on environmental conditions. We have
      tested the hypothesis that expression/accumulation of individual light harvesting
      complex (Lhc) proteins depends on plant growth conditions. Zea mays plants were
      grown in different temperature (13 degrees C vs. 24 degrees C) and light (high
      vs. low) conditions. The thylakoid membranes were isolated and fractionated by
      sucrose gradient and the protein content of the different bands was analyzed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Significant
      differences were found in the accumulation of both the major light harvesting
      complex of photosystem II (LHCII) complexes and the minor antenna chlorophyll
      proteins CP29, CP26 and CP24. In particular, temperature seems to play a major
      role in driving the expression/accumulation of the different proteins: the
      LHCII/minor antenna ratio increases with decreasing temperature. The pigment
      composition and the spectroscopic properties of LHCII complexes isolated from low
      temperature grown plants are significantly different from those of LHCII purified
      from high temperature grown plants. Two-dimensional maps show that different
      LHCII proteins are accumulated at different levels depending on growth
      conditions. Moreover the low temperature/high light grown plants show an
      increased value of nonphotochemical quenching. These results suggest a specific
      role of different LHCII complexes in the organization of the potosystem II and
      photoprotection.

PMID- 15714441
TI  - Effects of local anesthetics on human bladder contractility.
AB  - AIMS: We investigated the invitro effects of local anesthetics on the
      contractility of the human bladder. METHODS: By measuring the invitro isometric
      contractions of human bladder strips, we determined the effects of tetracaine,
      bupivacaine, lidocaine, and ropivacaine on the basal spontaneous contractions and
      contractions induced by various stimuli, namely, KCl (60 mM), carbachol (CCh),
      and electrical field stimulation (EFS). The effect of local anesthetic agents on
      Ca(2+)-independent sustained tonic contraction (SuTC) of the detrusor was also
      investigated. RESULTS: Local anesthetics increased phasic and tonic spontaneous
      contractile activity dose dependently in the concentration range 1-500 muM, but
      abolished phasic activity at higher concentrations. Local anesthetic agents
      inhibited nerve-mediated contraction (EFS, 0.8 msec) in a concentration-dependent
      manner (ropivacaine > tetracaine = bupivacaine > lidocaine), and inhibited non
      nerve mediated contractions induced by KCl, long pulse EFS (direct muscle
      stimulation, 100 msec), and CCh. Inhibitory potency on non-nerve mediated
      contraction was for long pulse EFS: ropivacaine = tetracaine > bupivacaine =
      lidocaine and for KCl- and CCh-induced contractions: ropivacaine > tetracaine >
      bupivacaine = lidocaine. Higher concentrations of local anesthetics were needed
      to inhibit non-nerve-mediated bladder contraction than nerve-mediated
      contraction. SuTC was suppressed by all local anesthetics concentration
      dependently. CONCLUSIONS: Our study demonstrates that local anesthetics have
      inhibitory effects on the contraction of human bladder as induced by different
      stimulants and concentrations. Their effects and differences suggest that they
      may be considered potentially useful as diagnostic and therapeutic agents for
      bladder dysfunction.

PMID- 15714444
TI  - Modification of biological parameters after treatment with recombinant factor
      VIIa in a patient with thrombocytopathy due to storage pool disease.
AB  - Patients with thrombocytopathy due to storage pool disease mostly suffer from
      mild bleeding diathesis. However surgical interventions can lead to excess
      bleeding. We describe how treatment with recombinant factor VIIa (Novoseven)
      during a surgical procedure in a boy with SPD leads to an immediate rise in PF-4,
      thereby activating factor Xa on the platelet surface, leading to active thrombin
      generation.

PMID- 15714445
TI  - Reduction of adult height in childhood acute lymphoblastic leukemia survivors
      after prophylactic cranial irradiation.
AB  - BACKGROUND: Impaired linear growth is a well-recognized complication in long-term
      childhood ALL survivors who received cranial irradiation. However, as many
      patients achieve a final height between the 5th and the 95th centile, the true
      incidence of linear growth impairment might be underestimated. METHODS: Reduction
      of adult height (RAH) was estimated in adult childhood ALL survivors with and
      without cranial irradiation. RAH was calculated as the difference between target
      height (TH) and final height (FH). TH was calculated according to the formula TH
      = {[(height father + height mother +/- 12)/2] + 3}. RAH was assessed in 79 adult
      childhood ALL survivors in first complete remission who had received cranial
      irradiation 25 Gy (Group I, n = 53), 18 Gy (Group II, n = 10) or chemotherapy
      alone (controls, n = 16). RESULTS: RAH was 8.6 +/- 8.2 cm in Group I (P = 0.001
      vs. controls), 6.2 +/- 3.2 cm in Group II (P = 0.01 vs. controls), and 1.7 +/-
      4.6 in controls (chemotherapy only). There was no significant difference between
      Group I and Group II. In Group I females had more RAH than males (P = 0.02). RAH
      was related to younger age at diagnosis (P = 0.001). CONCLUSIONS: The deficit
      between target height and final height highlights the reduction of adult height
      in the majority of male and female childhood ALL survivors who had received
      prophylactic cranial irradiation, in particular in those who were diagnosed at a
      younger age. This reduction would have been masked if patients FH was only
      compared with standard methods. RAH might be a sensitive predictor for growth
      hormone deficiency as these results suggest that radiation-induced growth hormone
      deficiency in these patients is the rule rather than the exception.

PMID- 15714446
TI  - Use of alternative and complementary therapies in children with cancer.
AB  - BACKGROUND AND OBJECTIVES: The use of complementary and alternative medicines
      (CAM) is becoming increasingly popular. Although considered beneficial by users,
      the potential for interaction or substitution with conventional treatment should
      not be overlooked by health care professionals. It is therefore important to gain
      insight into the prevalence and the factors related to the use of CAM. To
      establish the prevalence of use of CAM among children with cancer treated in a
      large pediatric hospital, describe the profile of use and factors related with
      use. As a secondary objective we aimed at measuring quality of life of the
      children aged 5 or more and compare the scores between users and non-users.
      METHODS: The study is a cross-sectional survey of parents whose child was treated
      at the oncology clinic or ward of Sainte-Justine Hospital, a large pediatric
      hospital in Montreal. Data on socio-demographic variables, the use of CAM and the
      quality of life was collected through a self-administered questionnaire. Quality
      of life was measured with the Child Health Questionnaire CHQ-PF50, while clinical
      data was collected from medical records. RESULTS: A total of 115 patients were
      recruited and 92 parents completed and returned the questionnaire, resulting in a
      80% response rate. According to this survey, 49% of the children used at least
      one type of CAM and 20% used herbal remedies/homeopathy/vitamins in the 2 months
      preceding the survey. Most popular CAM were spiritual/mental and physical
      strategies used by 35 and 33% of children under study, respectively. Only one
      parent reported having delayed a conventional treatment because of CAM. Although
      quality of life results must be interpreted with caution, they tend to favor non
      users. CONCLUSIONS: CAM is likely to be used by a wide variety of people. In our
      study, we found that about half of the children with cancer has used CAM in the 2
      preceding months. No specific profile of CAM users emerged from this study. The
      high prevalence of CAM warrants further studies to better understand the reasons
      and consequences of CAM use particularly on quality of life.

PMID- 15714448
TI  - Role of active follow-up for early diagnosis of relapse after elective end of
      therapies.
AB  - OBJECTIVE: To evaluate the role of active follow-up for the detection of relapses
      occurring after completion of therapy in children with cancer. METHODS: The
      clinical records of all children who had a cancer relapse more than 3 months
      after the end of therapies in the period 1985-2000 were reviewed. Relapses were
      defined "diagnosed at a scheduled visit" or "at an unscheduled visit" based upon
      how the visit that lead to the suspected diagnosis was scheduled. Information was
      collected on how the first suspicion of relapse was made. Survival after relapse
      was calculated, by type of visit and tumor type. RESULTS: Among 739 children who
      completed therapy for a malignant tumor in first complete remission (CR), 101
      relapses [74 after solid tumors (ST), 27 after leukemia/lymphoma (L)] occurred
      after a median time of 12 months (range 3-87). Fifty-one (50.5%) first relapses
      were diagnosed during a visit scheduled because of symptoms (36 ST, 15 L), and 50
      relapses (49.5%) at a regularly scheduled visit (38 ST, 12 L). Overall, 75% of
      relapses were first suspected on clinical basis, 16% via imaging, and only 9% via
      lab tests. Survival more than 10 years from first relapse was 25.7% (SE: 0.05%),
      with no significant differences between relapses diagnosed at a scheduled visit
      (20.5%), or at an unscheduled visit (32.1%; P = 0.826). Children with L had a
      better overall survival (OS, 70.6%) as compared to those with ST (9.2%, P <
      0.001), probably because of a more extensive use of stem cell transplantation
      (SCT) as part of the salvage regimens. CONCLUSIONS: Scheduled follow-up programs
      failed to detect relapses in 50% of cases presented here. Survival after relapse
      is not affected by whether relapse was detected at a scheduled or an unscheduled
      visit.

PMID- 15714447
TI  - Long-term complications in survivors of advanced stage neuroblastoma.
AB  - BACKGROUND: Few studies have assessed late effects in neuroblastoma (NB)
      survivors, particularly those with advanced stage disease. METHODS: Retrospective
      analysis of a cohort of advanced stage NB survivors followed in a late effect
      clinic at a single institution. Screening tests to detect late effects were
      tailored depending on the individual's treatment exposures. RESULTS: The study
      included 63 survivors (31 males). The median age at diagnosis was 3.0 years. The
      median follow-up from diagnosis was 7.06 years. All patients had surgery and
      received chemotherapy, 89% received radiation therapy (RT), 62% immunotherapy,
      and 56% autologous stem cell transplant. Late complications were detected in 95%
      of survivors and included: hearing loss (62%), primary hypothyroidism (24%),
      ovarian failure (41% of females), musculoskeletal (19%), and pulmonary (19%)
      abnormalities. The majority of complications were moderate, with only 4% being
      life-threatening. Survivors who received cisplatin were at greater risk to
      develop hearing loss compared to those not so treated (OR 9.74; 95% CI: 0.9
      101.6). A total dose of cyclophosphamide greater than 7.4 g was associated with
      ovarian failure (P = 0.02). CONCLUSIONS: Late complications occur frequently in
      survivors of advanced stage NB. The majority of these problems are of mild
      moderate severity. Long-term follow-up (LFTU) and screening of this population is
      essential.

PMID- 15714449
TI  - Serum creatinine: a surrogate measurement of lean body mass in children with
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Since creatinine is formed almost exclusively in skeletal muscle, the
      hypothesis of a relationship between serum creatinine (SC) and lean body mass
      (LBM), determined by dual-energy X-ray absorptiometry (DXA), was tested. METHODS:
      Two cohorts of patients were analyzed: 37 children with acute lymphoblastic
      leukemia (ALL) and 20 children with primary muscular disorders (PMD). The latter
      cohort was used as a comparative group. Statistical analyses were performed using
      linear regressions. RESULTS: A strong correlation was demonstrated between SC and
      LBM in the patients with PMD (r = 0.77) and in patients with ALL (r = 0.83 at
      diagnosis; r = 0.77 on therapy; and r = 0.56 off therapy). The correlation
      between SC and body size (body mass index) was much weaker (r = 0.38; r = -0.09;
      r = 0.29 at the successive observations in the ALL cohort and r = 0.05 in the PMD
      cohort). These data provide support for the initial hypothesis. CONCLUSIONS:
      Further investigations with a wider variety of diseases are needed for this will
      allow the consideration of SC as a general surrogate measure of LBM and
      consequently of nutritional status.

PMID- 15714450
TI  - Primary epithelial lung malignancies in the pediatric population.
AB  - BACKGROUND: Primary epithelial lung malignancies are rare in childhood and
      adolescence. We reviewed the Memorial Sloan-Kettering Cancer Center experience
      with these tumors to better understand their histology, time to diagnosis,
      treatment, and outcome. PROCEDURE: A retrospective review was performed on all
      patients 21 years of age or younger at diagnosis, treated for primary epithelial
      lung malignancies at Memorial Sloan-Kettering Cancer Center between 1980 and
      2001. RESULTS: We identified 11 patients with primary epithelial lung malignancy.
      The median age at diagnosis was 19 (range: 12-21) years. The most common
      radiographic abnormality was a mass (55%) on chest imaging. Seven patients (64%)
      were initially diagnosed as having pneumonia which contributed to a delay in
      diagnosis. Final pathologic diagnoses included adenocarcinoma (four), carcinoid
      tumor (three typical, one atypical), basaloid carcinoma (two), and mucoepidermoid
      carcinoma (one). A majority of patients presented with advanced disease (two
      stage III, four stage IV). Patients with localized disease were treated with
      surgical resection and all but one remains disease free with a median follow-up
      of 60 months (range: 13-286). Patients with either advanced locoregional or
      distant metastatic disease were treated with multimodal therapy and a majority
      had rapid progression of disease. CONCLUSIONS: When children and adolescents
      present with primary epithelial lung malignancy a majority will have advanced
      disease and experience a delay in diagnosis. The histologic types of tumors
      encountered are similar to lung tumors occurring in adults, although the
      frequency of the various types differs. Carcinoid tumors are more frequent, and
      less common subtypes of bronchogenic carcinoma are also more prevalent in the
      pediatric age group. Similar to the adult population, the prognosis of these
      tumors is dependent on histology and stage. Patients with carcinoid tumors seem
      to have the best prognosis, followed by adenocarcinoma. The highly aggressive
      basaloid carcinoma has the worst.

PMID- 15714451
TI  - Discrete stacking of large aromatic molecules within organic-pillared
      coordination cages.

PMID- 15714452
TI  - Going beyond the physical: instilling chirality onto the electronic structure of
      a metal.

PMID- 15714453
TI  - Controlling the catalytic activity of platinum-monolayer electrocatalysts for
      oxygen reduction with different substrates.

PMID- 15714454
TI  - The indium-mediated selective introduction of allenyl and propargyl groups at the
      C4-position of 2-azetidinones and the AuCl3-catalyzed cyclization of 4-allenyl-2
      azetidinones.

PMID- 15714456
TI  - Side-chain control of folding of the homologous alpha-, beta-, and gamma-peptides
      into "mixed" helices (beta-helices).
AB  - A systematic analysis of the substituent influence on the formation of the unique
      secondary structure type of "mixed" helices in the homologous alpha-, beta-, and
      gamma-peptides was performed on the basis of ab initio molecular orbital theory.
      Contrary to the common periodic peptide helices, mixed helices have an
      alternating periodicity and their hydrogen-bonding pattern is similar to those of
      beta-sheets. They belong, therefore, to the family of beta-helices. It is shown
      that folding of peptide sequences into mixed helices is energetically preferred
      over folding into their periodic counterparts in numerous cases. The influence of
      entropy and solvents on the formation of the various competitive mixed and
      periodic helix types is discussed. Among the oligomers of the various homologous
      amino acids, beta-peptides show the highest tendency to form beta-helices. The
      rules of substituent influence derived from the analysis of a wide variety of
      backbone substitution patterns might be helpful for a rational design of mixed
      helix structures, which could be important for mimicking membrane channels.

PMID- 15714455
TI  - Recruitment of dendritic cells in oral lichen planus.
AB  - Using immunohistochemistry the presence of different dendritic cell (DC) subsets
      was analysed in 16 biopsies from patients with oral lichen planus (OLP). A
      significant increase of CD1a+/Langerin+ Langerhans cells, DC-SIGN+ DC and
      CD123+/BDCA2+ plasmacytoid DCs (PDCs) was found in the epithelium and in the
      stroma of OLP biopsies compared to normal oral mucosa. A proportion of DCs were
      mature DC-LAMP+ and expressed S100 or CD11c, typically found in the
      interdigitating DCs of nodal T-cell areas. Double staining revealed that mature
      DCs co-expressed CCR7, thus indicating the development of a nodal migratory
      phenotype upon maturation. Significant recruitment of PDCs producing IFN-alpha
      was demonstrated by the expression of MxA within the lichenoid inflammatory
      infiltrate and close cell-to-cell contacts between PDCs and mature DCs were
      observed, with a significant correlation between the numbers of these two
      populations. Moreover, PDCs were also found to contain Granzyme-B, an associated
      cytotoxic granule protein, inducing target cell apoptosis. Taken together, these
      results suggest that PDCs may promote maturation of DCs and amplify the
      cytotoxicity of lymphoid cells. Finally, the recruitment of different subtypes of
      DC, such as Langerhans cells, stromal DC-SIGN+ DCs and PDCs, associated with a
      significant proportion of mature DCs, acquiring a CCR7+ 'migratory' phenotype,
      indicate that they may play a pivotal role in the development of the lichenoid
      inflammatory infiltrate that occurs typically in OLP.

PMID- 15714457
TI  - Mitochondrial DNA diversity in 17th-18th century remains from Tenerife (Canary
      Islands).
AB  - Mitochondrial DNA sequences and restriction fragment length polymorphisms were
      retrieved (with >80% efficiency) from a 17th-18th century sample of 213 teeth
      from Tenerife. The genetic composition of this population reveals an important
      ethnic heterogeneity. Although the majority of detected haplotypes are of
      European origin, the high frequency of sub-Saharan African haplotypes (15.63%),
      compared to that of the present-day population (6.6%), confirms the importance of
      the Canary Islands in the black slave trade of that epoch. The aboriginal
      substrate, inferred from the U6b1 haplotypes (8.59%), has also decreased due to
      European input. Finally, the presence of Amerindian lineages (1.5%) reveals that
      the Canary Islands have also received genetic flow from America.

PMID- 15714458
TI  - Replication-coupled modulation of early replicating chromatin domains detected by
      anti-actin antibody.
AB  - Evidence is presented for the reversible, cold-dependent immunofluorescence
      detection of the epitope (hereafter referred to as epiC), recognized by a
      monoclonal anti-actin antibody in diploid human fibroblast cell nuclei and
      mitotic chromosomes. The nuclear/chromosomal epiC was detected in a cell cycle
      window beginning in early S phase and extending through S phase, G(2) phase,
      mitosis until early G(1) phase of the subsequent daughter cells. A small but
      significant level of co-localization was measured between the nuclear epiC and
      active sites of DNA replication in early S phase. The level of co-localization
      was strikingly enhanced beginning approximately 1 h after the initial labeling of
      early S phase replicating chromatin domains. In contrast, epiC did not co
      localize with late S phase replicated chromatin either during DNA replication or
      at any other time in the cell cycle. We propose a replication-coupled modulation
      of early S phase replicated chromatin domains that is detected by the chromatin
      epiC positivity, persists on the chromatin domains from early S until early G(1)
      of the next cell generation, and may be involved in the regulation and/or
      coordination of replicational and transcriptional processes during the cell
      cycle. Further studies will be required to resolve the possible role of nuclear
      actin in this modulation process.

PMID- 15714459
TI  - Constitutive activation of phosphatidyl-inositide 3 kinase contributes to the
      survival of Hodgkin's lymphoma cells through a mechanism involving Akt kinase and
      mTOR.
AB  - The molecular mechanisms underlying the pathogenesis of the malignant
      Hodgkin's/Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL) are largely
      unknown. This study investigates the contribution of phosphatidyl-inositide 3
      kinase (PI3-kinase) and demonstrates that Akt, a substrate of PI3-kinase, is
      constitutively activated in HL-derived cell lines. Several downstream effectors
      of Akt signalling, including glycogen synthase kinase 3 (GSK-3) alpha and beta
      and mTOR substrates 4E-BP1 and p70 S6 kinase, were also phosphorylated in HL
      cells. The mTOR inhibitor, rapamycin, inhibited phosphorylation of these
      proteins. Furthermore, LY294002 inhibited phosphorylation of p70 S6 kinase and 4E
      BP1, suggesting that the phosphorylation of p70 S6 kinase and 4E-BP1 in HL cells
      is PI3-kinase dependent. Importantly, HRS cells of primary tumour samples not
      only expressed high levels of activated Akt but also displayed phosphorylation of
      downstream targets of Akt activation including GSK-3, 4E-BP1, and p70 S6 Kinase.
      Inhibition of PI3-kinase and mTOR showed only modest effects on cell survival at
      the lower serum concentrations. However, rapamycin and doxorubicin acted
      synergistically to reduce HL cell survival. A combination of rapamycin and
      chemotherapy should be investigated in the treatment of HL.

PMID- 15714460
TI  - DABCO-directed self-assembly of bisporphyrins (DABCO=1,4
      diazabicyclo[2.2.2]octane).
AB  - Three isomeric zinc bisporphyrins have been prepared by covalently linking
      together two aminoporphyrins with an isophthalic acid derivative. The porphyrins
      differ in the substitution pattern on the meso phenyl groups, that is, ortho,
      meta, or para. Titrations carried out by UV-visible and 1H NMR spectroscopy have
      been used to map out the stabilities and the stoichiometries of the complexes
      formed with 1,4-diazabicyclo[2.2.2]octane (DABCO) in chloroform. The ortho- and
      meta-substituted bisporphyrins form 1:1 intramolecular sandwich complexes. The
      para-substituted bisporphyrin cannot adopt the cofacial conformation required for
      this type of complex and forms a higher order 2:2 intermolecular assembly, which
      is stable over a wide range of DABCO concentrations.

PMID- 15714461
TI  - In vitro study of HIF-1 activation and VEGF release by bFGF in the T47D breast
      cancer cell line under normoxic conditions: involvement of PI-3K/Akt and MEK1/ERK
      pathways.
AB  - Hypoxia-inducible factor (HIF) is critical in the modulation of tumour
      angiogenesis in response to hypoxia. In the present study, the mechanisms
      underlying basic fibroblast growth factor (bFGF)-induced activation of HIF-1 and
      the subsequent release of vascular endothelial growth factor (VEGF) in a human
      breast cancer cell line (T47D) under normoxic conditions were explored. The data
      show that HIF-1alpha expression is induced by bFGF in a dose- and time-dependent
      fashion, while increased HIF-1alpha protein expression and transactivity of HIF-1
      are due to the phosphorylation of Akt by bFGF, as indicated by application of the
      phosphatidylinositol 3-kinase (PI-3K) inhibitor LY294002. The data also show that
      the MEK1 (mitogen-activated protein kinase kinase-1)/ERK (extracellular signal
      regulated kinase) pathway is only involved in bFGF-induced transactivity of HIF
      1, but not HIF-1alpha expression, indicating roles for both the PI-3K/Akt and the
      MEK1/ERK pathways in bFGF activity. In addition, the translation inhibitor
      cycloheximide confirmed that bFGF-induced HIF-1alpha protein expression was due
      to de novo protein synthesis. In contrast, p38 was not required for the
      expression of HIF-1alpha or HIF-1 transactivity, although significant
      phosphorylation of p38 was observed after bFGF treatment. Treatment of the cells
      with bFGF increased the amount of VEGF release, and this could be suppressed by
      either PD98059 or LY294002, suggesting the presence of a HIF-1alpha-dependent
      pathway for bFGF-induced VEGF production. In conclusion, the PI-3K/Akt and
      MEK1/ERK pathways, in a potentially independent and co-operative fashion, can
      modulate HIF-1 activation by bFGF. Further studies will pinpoint whether HIF-1 is
      the transcriptional factor responsible for the increased VEGF production
      following bFGF treatment of breast tumour cells.

PMID- 15714462
TI  - Toxic and repellent effects of Baccharis salicifolia essential oil on Tribolium
      castaneum.
AB  - Allelochemical effects were observed when Tribolium castaneum (Herbst) adults
      were treated with Baccharis salicifolia (Ruiz & Pavon) Pers essential oil. The
      main biological activities were toxicity and repellence. Terpenes present in the
      essential oil were identified by GC-MS, and some authentic samples were tested to
      assess their activity individually. The most acutely toxic compounds after 3 days
      were beta-pinene and pulegone. Most of the monoterpenes elicited symptoms
      indicative of neurotoxicity. The most repellent compound was alpha-terpineol.
      Toxic and repellent effects of chemical derivatives of the major sesquiterpene
      present in B salicifolia essential oil, as well as a series of monoterpenes, were
      evaluated in order to investigate structure-activity relationships. The reduced
      derivatives of the monoterpenes and sesquiterpenes were more repellent that their
      carbonyl analogues. In addition, unsaturation in the germacrane skeleton enhanced
      repellent activity.

PMID- 15714463
TI  - Controlled release of avermectin from porous hollow silica nanoparticles.
AB  - Porous hollow silica nanoparticles (PHSNs) with a diameter of ca 100 nm and a
      pore size of ca 4.5 nm were synthesized via a sol-gel route using inorganic
      calcium carbonate nanoparticles as templates. The synthesized PHSNs were
      subsequently employed as pesticide carriers to study the controlled release
      behaviour of avermectin. The avermectin-loaded PHSN (Av-PHSN) samples were
      characterized by BET, thermogravimetric analysis and IR, showing that the amount
      of avermectin encapsulated in the PHSN carrier could reach 58.3% w/w by a simple
      immersion loading method, and that most of the adsorption of avermectin on the Av
      PHSN carrier might be physical. Avermectin may be loaded on the external surface,
      the pore channels in the wall and the inner core of the PHSN carriers, thus
      leading to a multi-stage sustained-release pattern from the Av-PHSN samples.
      Increasing pH or temperature intensified the avermectin release.

PMID- 15714464
TI  - A proteomic approach to studying biogenic amine producing lactic acid bacteria.
AB  - All fermented foods are subject to the risk of biogenic amine contamination.
      Histamine and tyramine are among the most toxic amines for consumers' health,
      exerting undesirable effects on the central nervous and vascular systems, but
      putrescine and cadaverine can also compromise the organoleptic properties of
      contaminated foods. These compounds are produced by fermenting microbial flora
      that decarboxylate amino acids to amines. Little is known of the factors which
      induce biosynthesis of decarboxylating enzymes and/or which modulate their
      catalytic activity: the accumulation of amines is generally considered to be a
      mechanism that contrasts an acidic environment and/or that produces metabolic
      energy through coupling amino acid decarboxylation with electrogenic amino
      acid/amine antiporters. Two Lactobacillus strains, Lactobacillus sp. 30a (ATCC
      33222), and a Lactobacillus sp. strain (w53) isolated from amine-contaminated
      wine, carrying genetic determinants for histidine decarboxylase (HDC) and
      ornithine decarboxylase (ODC), were studied and the influence of some
      environmental and nutritional parameters on amine production and protein
      biosynthesis was analyzed through a proteomic approach; this is the first report
      of a proteomic analysis of amine-producing bacteria. HDC and ODC biosynthesis
      were shown to be closely dependent on the presence of high concentrations of free
      amino acids in the growth medium and to be modulated by the growth phase. The
      stationary phase and high amounts of free amino acids also strongly induced the
      biosynthesis of an oligopeptide transport protein belonging to the proteolytic
      system of Lactic Acid Bacteria. At least two isoforms of glyceraldehyde-3
      phosphate dehydrogenase, with different M(r), pI and expression profiles, were
      identified from Lactobacillus sp. w53: the biosynthesis of one isoform, in
      particular, is apparently repressed by high concentrations of free amino acids.
      Other proteins were identified from the Lactobacillus proteome, affording a
      global knowledge of protein biosynthesis modulation during biogenic amine
      production.

PMID- 15714465
TI  - Long-term evaluation of compliance with refuge requirements for Bt cotton.
AB  - The success of the refuge strategy for delaying pest resistance to Bt crops
      depends on compliance by farmers. However, the accuracy of previous estimates of
      compliance has been questioned. We have applied a novel approach based on the use
      of Geographical Information System (GIS) technology to measure compliance with
      refuge requirements for Bt cotton in six Arizona regions from 1998 to 2003.
      Although compliance varied among regions, overall compliance was above 88% in
      five of six years. With the cooperation of farmers, our approach allows precise
      and economical assessment of compliance with the refuge strategy.

PMID- 15714466
TI  - Cytokines and growth factor modulators in intestinal inflammation and repair.
AB  - Breakdown in gastrointestinal mucosal integrity may be due to increased
      aggressive factors, including an excessive inflammatory response, decreased
      mucosal defence or a combination of the two. Our understanding of the control
      processes underlying these changes has rapidly expanded over the last decade and
      it is becoming clear that rather than being distinct elements, inflammation and
      repair are interrelated processes mediated by common cytokines and growth
      factors, with the division of factors as being a cytokine or a growth factor
      being somewhat artificial. The use of biological therapies, such as antibodies
      that cause receptor blockade or administering recombinant growth factors, has now
      progressed from the laboratory to the clinical arena. This review summarizes
      current thoughts on the use of these factors in general, but with particular
      emphasis on inflammatory bowel disease.

PMID- 15714471
TI  - Glutathione S-transferase tissue profiling by reporter peptide monitoring.
AB  - Glutathione S-transferases (GSTs) form a widespread enzyme superfamily mainly
      involved in phase II detoxification. Differential expression of the various GST
      isoforms, differing in catalytic and structural properties, correlates with
      physiological and pathological states. Fast and simple determination of the GST
      profile is expected to be an important diagnostic tool in disease analysis. Here
      we propose a combined approach of high resolution separation techniques and
      electrospray mass spectrometric analyses for characterizing the spectrum of GSTs
      in male mouse liver. In this approach, the sensitivity and speed required for
      tissue GST profiling studies is achieved by tracking the reconstructed ion
      current of selected reporter peptides following chromatographic separation. This
      simple procedure, in which an affinity protein bait is followed by a chemical
      fragmentation and mass spectrometric analysis, could be sufficiently sensitive to
      detect the qualitative differences between physiological and pathological states.

PMID- 15714472
TI  - Sequence tag scanning: a new explorative strategy for recognition of unexpected
      protein alterations by nanoelectrospray ionization-tandem mass spectrometry.
AB  - Protein analysis by database search engines using tandem mass spectra is limited
      by the presence of unexpected protein modifications, sequence isoforms which may
      not be in the protein databases, and poor quality tandem mass spectrometry
      (MS/MS) of low abundance proteins. The analysis of expected protein modifications
      can be efficiently addressed by precursor ion scanning. However, it is limited to
      modifications that show such a characteristic loss in a peptide independent
      manner. We observed that proline and aspartic acid induced backbone fragmentation
      is accompanied by a low intensity signal for loss of H3PO4 for several pSer- or
      pThr-phosphopeptides. We describe here the use of peptide-specific fragments that
      can be used after a protein was identified to allow in-depth characterization of
      modifications and isoforms. We consider high abundance fragments formed by
      cleavage at the C-terminal side of aspartic acid, at the N-terminal side of
      proline and low mass ions such as a2, b2, b3, y1, y2, and y3. The MS/MS dataset
      is filtered for each sequence tag of interest by an in silico precursor ion scan.
      The resulting extracted ion traces are then combined by multiplication to
      increase specificity. Since the strategy is based on common peptide segments
      which are shared by different isoforms of peptides it can be applied to the
      analysis of any post-translational modification or sequence variants of a
      protein. This is demonstrated for the cases of serine and threonine
      phosphorylation, histone H1 acetylation and the spotting of multiple H1 isoforms.

PMID- 15714473
TI  - Analysis of the composition of an immunoglobulin E reactive high molecular weight
      protein complex of peanut extract containing Ara h 1 and Ara h 3/4.
AB  - Peanuts (Arachis hypogaea) contain some of the most potent food allergens. In
      recent years an increasing prevalence of peanut allergies both in children and
      adults has been observed in the USA and in Europe. In vitro identification and
      characterization of allergens including those from peanut have been frequently
      performed by Western blotting. However this method may alter the immunoglobulin E
      (IgE) antibody reactivity since the proteins are denatured by detergent treatment
      and/or reduction of disulfide bonds by reducing reagents and does not answer the
      question how peanut allergens interact with the human digestive apparatus and
      immune system. Size exclusion chromatography of peanut extract shows that
      approximately 90% of the total protein content is eluted as one peak in the
      exclusion volume with a molecular mass of over 200 kDa. The proteins of this
      fraction were analyzed by blue-native polyacrylamide gel electrophoresis (PAGE),
      immunoblotting, two-dimensional PAGE and Western blotting. A complex of Ara h 1
      (Acc. no. P43237), Ara h 3/4 (AAM46958), Ara h 3 (AAC63045), Ara h 4 (AF086821),
      Gly 1 (AAG01363) and iso-Ara h 3 (AAT39430) was identified using patients' IgE
      and allergen-specific monoclonal antibodies; N-terminal sequencing and matrix
      assisted laser desorption/ionisation-time of flight analysis verified these
      findings. A comparison of the peanut allergen sequences of Ara h 3/4, Ara h 3,
      Ara h 4 and peanut trypsin inhibitor (AF487543) and the proteins Gly 1 and iso
      Ara h 3, not yet described as allergens, leads to the conclusion that these
      proteins are isoallergens of each other. It was shown that these isoallergens are
      post-translationally cleaved and held together by disulfide bonds in accordance
      to the 11S plant seed storage proteins signature.

PMID- 15714474
TI  - Analysis of genotoxicity and the carcinogenic mode of action for ortho
      phenylphenol.
AB  - Ortho-phenylphenol (OPP) and its sodium salt (SOPP) are commercial products that
      have wide human exposure and have been shown in several studies to be rodent
      carcinogens. Genetic toxicology data were assessed in an attempt to understand
      the carcinogenic mode of action of OPP and SOPP. More than 130 studies were
      evaluated to determine if OPP, SOPP, or any of their enzymatic or nonenzymatic
      breakdown products react directly with DNA to induce mutation, changes in
      chromosome structure or number, DNA repair, or nonspecific DNA damage including
      strand breakage or covalent binding. The genotoxicity databases for OPP and SOPP
      are not only large but heterogeneous, requiring weight-of-evidence methods to
      arrive at a conclusion regarding their genotoxic properties and potential.
      Evidence derived from the available studies leads to the conclusion that study
      results showing OPP/SOPP directly interacting with DNA are equivocal.
      Clastogenicity was the most consistent type of genetic toxicity produced by
      OPP/SOPP (and their break-down products) and was consistently associated with
      other intracellular preneoplastic toxicity produced at super-threshold
      concentrations. The weight of evidence from the combined database supports the
      hypothesis that OPP/SOPP-induced DNA damage is a threshold-dependent response
      associated with target tissue toxicity, most likely induced by their breakdown
      products phenylhydroquinone and phenylbenzoquinone. It is possible that this
      threshold-dependent clastogenicity could contribute to the carcinogenic mode of
      action for OPP or SOPP.

PMID- 15714475
TI  - Adenocarcinoma of the nose and paranasal sinuses: a retrospective study of
      diagnosis, histologic characteristics, and outcomes in 24 patients.
AB  - BACKGROUND: Adenocarcinomas of the sinonasal cavity are unusual tumors with
      variable clinical courses. METHODS: We conducted a retrospective chart review
      between 1980 and 2001. RESULTS: Twenty-four patients (17 men) with sinonasal
      adenocarcinoma were identified. Nasal obstruction was the most common presenting
      symptom (75%), and the nose was the most common site of involvement (83%). Eleven
      tumors (46%) were high grade (grade 3 or 4). Twenty-three patients (95%)
      underwent an attempt at surgical excision with tumor recurrence or residual
      disease in seven. Age and tumor grade were associated with overall survival, and
      tumor grade and intracranial extension were associated with death from disease.
      CONCLUSIONS: Presentation and treatment for nasal adenocarcinoma varies widely.
      Some low-grade variants of nasal adenocarcinomas seem to be associated with a
      more favorable prognosis and, depending on the extent of the tumor, can be
      treated with less-aggressive therapy.

PMID- 15714478
TI  - Experimental infection of pigtailed macaques with a simian rotavirus, YK-1.
AB  - Experimental rotavirus infection was investigated in pigtailed macaques to study
      the infectivity, immunity, and pathogenesis of rotavirus. A challenge virus, YK
      1, was administered intragastrically to four seronegative macaques (age: 11-16
      months). Although none of the monkeys developed diarrhea, an active infection
      occurred with high titers of rotavirus antigen detected in stools 2-10 days after
      challenge. These animals developed rotavirus-specific antibody responses similar
      to those seen following primary exposure to rotavirus. YK-1 was then inoculated
      in four seropositive macaques (age: 14-16 months). All animals shed viral antigen
      in their stool, but the titers and duration were significantly less when compared
      to seronegative macaques. When rechallenged 28 days after initial YK-1 challenge,
      the macaques demonstrated significant protection against reinfection. All
      seropositive animals developed a rise in rotavirus-specific serum and fecal
      antibodies during YK-1 challenge and rechallenge. To independently assess the
      role of age and preexisting IgG titers to rotavirus, a 4-month-old seronegative
      and 6-month-old seropositive macaque were inoculated with YK-1. The seronegative
      macaque shed high titers of virus for 9 days, while the seropositive macaque shed
      only 3 days and in low titer. These data suggest that a primate model of
      rotavirus infection using the YK-1 strain may be useful in examining the immune
      response and protection from infection in pigtailed macaques and indicate that
      levels and duration of shedding may provide a good measure of protection from
      natural infection and from that induced by oral or parenteral vaccines.

PMID- 15714477
TI  - Enhanced binding of dopamine D1 receptors in caudate-putamen subregions in High
      Yawning Sprague-Dawley rats.
AB  - Previous reports have shown that the inbred High-Yawning (HY) and Low-Yawning
      (LY) rats differ in several behavioral characteristics related to mesolimbic and
      nigrostriatal dopamine (DA) function. To determine if differential expression of
      DA receptors or DA transporter may mediate the behavioral differences in these
      two sublines of the Sprague-Dawley rat, we performed a quantitative
      autoradiography study of the DA D1-like, D2-like, and DA-transporter binding in
      the basal ganglia and nucleus accumbens. The results show that levels of the D1
      binding in the caudate-putamen of the HY rat were higher than in the LY animals,
      whereas no significant differences in the DA D2 receptors and DA transporter were
      noted in these sublines. These data suggest that the differences in DA receptors
      in D1 binding in HY rats may in part have contributed to the behavioral
      differences related to DA functions such as grooming and penile erection. Our
      findings are consistent with previous reports showing a decrease in the
      behavioral responses after systemic administration of DA agonist in LY compared
      to HY rats.

PMID- 15714479
TI  - Participation of dorsal raphe nucleus in the behavioral alteration observed after
      discontinuation of chronic diazepam administration: possible neural circuitry
      involved.
AB  - Previous findings from our laboratory have demonstrated a positive correlation
      between the development of tolerance to diazepam (DZ) 5 mg/kg/day over 4 days,
      and increased hippocampal synaptic plasticity. It seems likely that a similar
      plastic phenomenon may occur on hippocampal formation after chronic (18 days) DZ
      administration. We postulate hippocampal long-term potentiation (LTP) underlying
      substrate to the behavioral alteration observed after chronic DZ administration.
      In the present study, we investigated the involvement of the serotonergic (5-HT)
      system in the possible neural circuitry recruited during DZ withdrawal and in the
      increased hippocampal synaptic plasticity associated with the discontinuation of
      chronic DZ administration. The results of the current research demonstrate an
      increased neuronal activity in the dorsal raphe nucleus (DRN) during withdrawal.
      Previous MK-801 administration impairs the development of anxiety signs observed
      during withdrawal and the concomitant increased electrical activity on 5-HT
      neurons on DRN. These results are discussed in terms of the participation of 5-HT
      system in the modulation of hippocampal plasticity developed on DZ withdrawal.

PMID- 15714480
TI  - The importance of HCV on the burden of chronic liver disease in Italy: a
      multicenter prevalence study of 9,997 cases.
AB  - Knowledge of the current epidemiology of chronic liver disease in Italy is mostly
      obsolete and fragmentary for the lack of up-to-date consistent data. In 2001, a 6
      month prevalence study was undertaken in 79 hospitals to assess the
      characteristics of chronic liver disease in Italy. Both prevalent and incident
      cases were enrolled. A total of 9,997 patients were recruited, of whom 939 (9.4%)
      had normal liver biochemistry, 6,210 (62.1%) had chronic hepatitis, 1,940 (19.4%)
      had liver cirrhosis, and 341 (3.4%) had hepatocellular carcinoma (HCC). In 567
      patients (5.7%) the diagnosis was not established. Hepatitis C virus (HCV) was
      found in 69.9% of the patients and was the only etiological factor in 56.3% of
      all the patients. Hepatitis B surface antigen (HBsAg) was present in the serum of
      13.4% of the cases (in 10% it was the only etiological factor). A history of
      alcohol abuse was found in 23% of the cases (9.4% without viral infection). The
      prevalence of HCV-related cases was significantly lower in incident than in
      prevalent cases (44.9% vs. 59.9%, P < 0.0001), while the proportion of patients
      with alcohol abuse was much higher in incident than in prevalent cases (18.1% vs.
      6.6%, P < 0.0001). These findings indicate that nearly one quarter of patients
      with chronic liver diseases in Italy have a severe disease such as liver
      cirrhosis and HCC represents a not negligible burden for the national health
      system. Hepatitis B fell in importance as an etiological factor. Hepatitis C is
      the important pathogenic factor for chronic liver disease in Italy. However, a
      comparison between the prevalent and incident cases suggests that in future HCV
      infection will also play a progressively decreasing role, in part as a
      consequence of treatment.

PMID- 15714481
TI  - Outbreak of acute hemorrhagic conjunctivitis in French Guiana and West Indies
      caused by coxsackievirus A24 variant: phylogenetic analysis reveals Asian import.
AB  - An outbreak of acute hemorrhagic conjunctivitis occurred in French Guiana between
      April and July 2003, with approximately 6,000 cases in the two major cities
      Kourou and Cayenne. Since acute hemorrhagic conjunctivitis is not a notifiable
      disease in France, there was no registration of the number of cases. Therefore,
      these were estimated by comparing the consumption of antibiotic eye drops and
      ophthalmic ointments during 2002 and 2003. The outbreak rapidly spread into the
      Caribbean Islands, causing an outbreak in Guadeloupe in October. Viral isolates
      from conjunctival swabs of 16 patients were confirmed to be enterovirus by PCR
      directed to the 5' UTR of the genome. The isolates could not be neutralized by
      the Melnick intersecting pools, but were shown to be CV-A24 variant by limited
      sequencing within the VP1 and 3C regions of 12 strains. Phylogenetic analysis
      revealed that they were similar to the genotype III strains causing outbreaks in
      Korea 2002 and Malaysia 2003. The previous outbreak of conjunctivitis caused by
      CV-A24 in the Caribbean in the 1980s was also introduced from Asia, and
      disappeared after 3 years. This new introduction from Asia and its rapid spread
      into the Caribbean, where the infection disappeared after a few months, indicates
      that the CV-A24 variant has a different epidemiological pattern in this region
      compared to South East Asia, since it has not established an endemic infection.
      It had to be reintroduced from Asia, where it has been circulating since the
      1970s.

PMID- 15714482
TI  - Comparison of loop-mediated isothermal amplification, real-time PCR, and virus
      isolation for the detection of herpes simplex virus in genital lesions.
AB  - This study compares herpes simplex virus (HSV) type-specific loop-mediated
      isothermal amplification (LAMP) with virus isolation and real-time PCR. Genital
      tract specimens were obtained from 25 patients with genital lesions; two swab
      samples were collected from the vulva and cervix of each patient, for a total of
      50 specimens. After culturing, 10 of 50 (20%) samples were positive for HSV-1 and
      12 of 50 (24%) samples were positive for HSV-2. None of the patients excreted
      both HSV-1 and HSV-2 virus. An original HSV type-specific LAMP assay (30 min
      reaction) was compared with virus isolation and HSV type-specific real-time PCR.
      Viral DNA was detected by LAMP in 9 of 10 HSV-1 isolated samples and 11 of 12 HSV
      2 isolated samples. No viral DNA was detected in samples without virus isolation.
      Thus, if virus isolation was used as the standard method, the LAMP protocol was
      highly sensitive and specific. In comparing LAMP to real-time PCR, viral DNA was
      detected by the LAMP method in 9 of 12 HSV-1 DNA positive samples and 11 of 18
      HSV-2 DNA positive samples. If real-time PCR was used as the standard method,
      then, sensitivity of the LAMP method (in particular, for HSV-2) was low. Taking
      this into consideration, the LAMP reaction was extended to 60 min. This led to an
      increase in sensitivity, resulting in an additional one and three samples testing
      positive for HSV-1 LAMP and HSV-2 LAMP, respectively, compared to the original
      LAMP protocol. Therefore, the sensitivity of the LAMP method increased to about
      80%.

PMID- 15714483
TI  - HIV-1 subtypes and circulating recombinant forms (CRFs) from HIV-infected
      patients residing in two regions of central and southern Italy.
AB  - A total of 347 pol gene sequences from 88 Tuscan and 259 Apulian subjects
      (including 52 non-Italians and 9 children) were analyzed phylogenetically. Forty
      four (12.6%) non-B subtypes were found, including 3.4% C, 1.4% F1, 0.8% G, and
      0.3% each for J and A pure subtypes, and 3.7% CRF02_AG, 1.4% CRF01_AE, 0.6% BF,
      and 0.3% CRF06-cpx recombinant forms. An additional sample close-matched the pol
      gene of an unique recombinant form (URF AGK 99GR303). The non-B subtypes were
      from 40 adults and 4 children; 12 of these 44 patients were epidemiologically
      linked. Thirty-three of the 44 non-B viruses pertained to non-Italian immigrants
      and 11 to Italians, signifying that 63.4% immigrants and 3.7% Italians harbored
      non-B subtypes. The overall frequency of non-B subtypes was higher in Tuscany
      than in Apulia (18.1% vs. 10.8%). Moreover, 6.1% and 3.0% non-B subtypes were
      found among Italians from Florence and Apulia, respectively, while 52.1% and
      72.4% of immigrants living in Tuscany and Apulia harbored non-B subtypes. Women
      infected by means of sexual contact prevailed among non-Italian adults; the
      majority of Italians were males and admitted high-risk sexual behavior. Four
      Italians had a history of extensive travel in countries of high endemicity.
      Social and epidemiological changes are responsible for an increasing circulation
      of non-B subtypes in Italy. Although non-B subtypes principally infect non
      Italian patients, in Italy they can no longer be considered exclusively
      restricted to subjects from endemic areas.

PMID- 15714484
TI  - Phenotypic and genetic changes in coxsackievirus B5 following repeated passage in
      mouse pancreas in vivo.
AB  - Common enterovirus infections appear to initiate or facilitate the pathogenetic
      processes leading to type 1 diabetes, and also sometimes precipitate the clinical
      disease. In experimental infection of mice, coxsackieviruses have shown to have a
      strong affinity for the exocrine tissue, while even in lethal cases, the islets
      remain unaffected. The virus strain most intensively studied in this respect is
      the diabetogenic variant E2 of coxsackievirus B4. In addition, it is known that
      all six serotypes of coxsackie B viruses can be made diabetogenic by repeated
      passages in either mouse pancreas in vivo or in cultured mouse beta-cells in
      vitro. However, the genetic determinants of the phenomenon have not been
      determined. In the present study, a laboratory strain of coxsackievirus B5 was
      passaged repeatedly in mouse pancreas in vivo. After 15 passages, the virus
      phenotype was clearly changed and infection of the variant resulted in a diabetes
      like syndrome in mice characterized by chronic pancreatic inflammation together
      with dysregulation in glucose metabolism, loss of pancreatic acinar tissue, and
      mild insulitis. In order to characterize the genetic determinants involved in
      mouse pancreas adaptation, the passaged virus variant together with the parental
      virus strain was cloned for molecular characterization. The whole genome
      sequencing of both virus strains revealed only limited differences. Altogether,
      eight nucleotides were changed resulting in five amino acid substitutions, of
      which three were located in the capsid proteins.

PMID- 15714485
TI  - Inter- and intra-person cytomegalovirus infection in Malawian families.
AB  - Sequence polymorphisms in the gN and gO genes of cytomegalovirus (CMV) amplified
      from mouth rinse and urine samples of 19 Malawian patients with Kaposi's sarcoma
      (KS) and 58 of their first-degree relatives were investigated. CMV-DNA was
      amplified from 41 people (53%) from either the gN or gO region in at least one
      sample, from 14 people (18%) in both domains in at least one sample, and from 13
      (17%) in either domain in both samples. Twenty-one (51%) were seropositive for
      human immunodeficiency virus-1 (HIV). Identical gN sequences were recovered from
      eight families and non-identical sequences in six, while identical gO sequences
      were found in three families and non-identical sequences in five. Five people,
      four of whom were children, each carried multitypic gN sequences or gO sequences.
      The findings are consistent with CMV spread along intra- and extra-household
      routes, and with multiple intra-host CMV infection.

PMID- 15714486
TI  - Comparison of three different serological techniques for primary diagnosis and
      monitoring of nasopharyngeal carcinoma in two age groups from Tunisia.
AB  - Nasopharyngeal carcinoma (NPC) in Tunisia is characterized by its bimodal age
      distribution involving juvenile patients of 10-24 years and adult patients of 40
      60 years. Three serological techniques were compared for primary diagnosis (N =
      117) and post-treatment monitoring (N = 21) of NPC patients separated in two age
      groups. Immunofluorescence assay (IFA) was used as the "gold standard" for
      detection of IgG and IgA antibodies reactive with Epstein-Barr virus (EBV) early
      (EA) and viral capsid (VCA) antigens. Results were compared with ELISA measuring
      IgG and IgA antibody reactivity to defined EBNA1, EA, and VCA antigens.
      Immunoblot was used to reveal the molecular diversity underlying the anti-EBV IgG
      and IgA antibody responses. The results indicate that young NPC patients have
      significantly more restricted anti-EBV IgG and IgA antibody responses with
      aberrant IgG VCA/EA levels in 78% compared to 91.7% in elder patients. IgA VCA/EA
      was detected in 50% of young patients versus 89.4% for the elder group (P <
      0.001). Immunoblot revealed a reduced overall diversity of EBV antigen
      recognition for both IgG and IgA in young patients. A good concordance was
      observed between ELISA and IFA for primary NPC diagnosis with 81-91% overall
      agreement. Even better agreement (95-100%) was found for antibody changes during
      follow-up monitoring, showing declining reactivity in patients in remission and
      increasing reactivity in patients with persistent disease or relapse. ELISA for
      IgA anti-VCA-p18 and immunoblot proved most sensitive for predicting tumor
      relapse. VCA-p18 IgA ELISA seems suitable for routine diagnosis and early
      detection of NPC complication.

PMID- 15714487
TI  - Effective poxvirus removal by sterile filtration during manufacture of plasma
      derivatives.
AB  - As a consequence of the September 2001 terrorist events, programs to protect
      against further such acts including potentially the use of biological warfare
      agents have been launched in the USA and elsewhere. As part of these initiatives,
      Vaccinia virus was procured for the pre-emptive vaccination of key personnel
      against smallpox as well as population-wide protection after an eventual
      exposure. The introduction of this live virus into a population at a relatively
      large scale represents a theoretical challenge for the safety of the blood
      supply, and potentially for plasma for fractionation. To strengthen further the
      demonstration of safety margins for plasma derived products against Vaccinia
      virus, the capacity of sterile filtration procedures to remove the virus was
      investigated. An infectivity assay for the Vaccinia virus strain which represents
      the majority of smallpox vaccine stocks available currently was used to
      investigate the potential removal of this virus by sterile filtration processes
      during the manufacture of plasma derivatives. Vaccinia virus behaves as predicted
      based on its size, i.e., an artificially added virus load is removed about 10,000
      fold by the sterile filtration procedures tested. As the current investigation
      covered a range of different protein concentrations, filter materials and filters
      from different manufacturers, the results obtained are considered to be widely
      applicable. The current investigation supports further the high safety margins of
      plasma derivatives against any potential Vaccinia virus content of plasma for
      fractionation. As the large size is a general feature of Orthopox viruses, the
      results would also provide assurance against poxviruses identified more recently,
      for example, Monkeypox virus.

PMID- 15714488
TI  - Mutations in the nonstructural region 5B of hepatitis C virus genotype 1b: their
      relation to viral load, response to interferon, and the nonstructural region 5A.
AB  - The nonstructural 5B (NS5B) protein of hepatitis C virus possesses RNA-dependent
      RNA polymerase activity and plays an essential role in viral replication. The
      mutations in NS5B were determined and the correlation with viral load and
      response to interferon (IFN) were assessed. The entire NS5B region in 33 patients
      and its thumb domain in 62 patients was sequenced. The number of amino acid
      substitutions in the NS5B protein, that in thumb domain and the substitution at
      aa 389 was correlated with viral load and the response to IFN. Multivariate
      analysis selected only mutation in IFN sensitivity determining region (ISDR) as a
      factor associated with the viral load and response to IFN. The number of
      substitutions in the thumb domain and the substitution at aa 389 correlated with
      the number of substitutions in the ISDR. These results suggest that mutations in
      NS5B, especially in the thumb domain and at aa 389, have an important effect on
      viral load and the response to IFN, although they were dependent on mutations in
      ISDR. Further studies on the relationship between NS5B and NS5A (ISDR) are
      necessary to elucidate the mechanism of the correlation with viral load and the
      response to IFN.

PMID- 15714490
TI  - Favorable efficacy of long-term lamivudine therapy in patients with chronic
      hepatitis B: an 8-year follow-up study.
AB  - The long-term efficacy of lamivudine therapy in patients with hepatitis B virus
      (HBV) infection is still not clear. In this study, 20 non-cirrhotic Japanese
      patients infected with HBV received lamivudine therapy for more than 1 year and
      were followed for a median period of 8.5 years (range, 6.7-8.7 years). The rates
      of HBe antigen (HbeAg) negative, HBV-DNA undetectable, and alanine
      aminotransferase (ALT) normal level at the start of lamivudine were 55%, 25%, and
      20% and 85%, 80%, and were 80%, respectively, at the last visit, including
      patients who received additional treatment. The values at the last visit tended
      to and were significantly higher than those at the start. The values improved at
      the last visit regardless of the emergence of YMDD motif mutant and continuation
      of lamivudine. YMDD mutant and biochemical relapse with mutant virus
      (breakthrough hepatitis) appeared in 65% and 45% during follow-up, respectively,
      but severe breakthrough hepatitis occurred in only 5%. Furthermore, 80% of
      patients who received additional treatment for breakthrough hepatitis, regardless
      of continuation of lamivudine, were ALT normal level at the last visit, in
      contrast to 25% untreated. HBsAg clearance occurred in two patients of the
      discontinuous lamivudine group with non-vertical transmission, who were
      relatively young. One was infected with HBV genotype C with breakthrough
      hepatitis and the other had no YMDD mutant and was infected with genotype D, a
      rare type in Japan. None developed cirrhosis or hepatocellular carcinoma (HCC)
      during follow-up. Our results suggest that long-term lamivudine therapy improves
      long-term prognosis, especially when additional treatment for breakthrough
      hepatitis is used.

PMID- 15714491
TI  - Serological markers of hepatitis B, C, and E viruses and human immunodeficiency
      virus type-1 infections in pregnant women in Bali, Indonesia.
AB  - Except for hepatitis B virus (HBV), there have been few data on serological
      markers of hepatitis viruses such as hepatitis C virus (HCV) and E virus (HEV),
      and human immunodeficiency virus type-1 (HIV) in Bali, Indonesia. During 5 months
      from April to August 2003, sera were collected from 2,450 pregnant women at eight
      jurisdictions in Bali, and they were tested for markers of these viruses. Only
      one (0.04%) was positive for antibody to HCV, but none for antibody to HIV.
      Hepatitis B surface antigen (HBsAg) was detected in 46 (1.9%) at a prevalence
      significantly lower than that in 271 of the 10,526 (2.6%) pregnant women in Bali
      surveyed 10 years previously (P < 0.045). The prevalence of hepatitis B e antigen
      in pregnant women with HBsAg decreased, also, from 50% to 28% during the 10 years
      (P < 0.011). Antibody to HEV (anti-HEV) was examined in 819 pregnant women who
      had been randomly selected from the 2,450. The overall prevalence of anti-HEV was
      18%, and there were substantial regional differences spanning from 5% at Tabanan
      district to 32% at Gianyar district. Furthermore, the prevalence of anti-HEV
      differed substantially by their religions. In the Sanglah area of Denpasar City,
      for instance, anti-HEV was detected in 20 of the 102 (20%) Hindus, significantly
      more frequently than in only 2 of the 101 (2.0%) Muslims (P < 0.001). Swine that
      are prohibited to Muslims, therefore, is likely to serve as a reservoir of HEV in
      Bali. In conclusion, HBV is decreasing, HCV and HIV have not prevailed, as yet,
      while HEV is endemic probably through zoonotic infection in Bali.

PMID- 15714489
TI  - Hepatitis C virus genotype distribution in China: predominance of closely related
      subtype 1b isolates and existence of new genotype 6 variants.
AB  - To determine hepatitis C virus (HCV) genotype distribution in China, a total of
      148 HCV RNA positive serum samples were collected from nine geographic areas and
      subjected to RT-PCR followed by direct DNA sequencing and phylogenetic analysis
      of the core, E1, and NS5B regions. HCV was genotyped in 139 (93.9%) samples.
      Among them subtype 1b was the most predominant [66% (92/139)] followed by 2a [14%
      (19/139)]. Of 92 subtype 1b isolates, 35 (38%) and 30 (33%) formed two clusters,
      designated groups A and B. Group A was prevalent throughout China, while group B
      was predominant in the central and southern regions. In three cities in the Pearl
      River Delta, subtype 6a replaced 2a as the second most predominant subtype, and
      in Kunming (southwest) multiple HCV genotypes/subtypes were present. New variants
      of HCV genotype 6 were discovered in three samples from Kunming and one in
      Guangzhou in the Pearl River Delta.

PMID- 15714492
TI  - Hepatocyte steatosis is an important predictor of response to interferon (IFN)
      monotherapy in Japanese patients infected with HCV genotype 2a: Virological
      features of IFN-resistant cases with hepatocyte steatosis.
AB  - The role of hepatocyte steatosis in interferon (IFN) resistance is still unclear,
      especially in patients infected with hepatitis C virus (HCV) genotype 2a. The
      present study was conducted in 364 consecutive non-cirrhotic naive patients
      infected with genotype 2a, who were evaluated for the severity of steatosis and
      response to IFN monotherapy after a 24-week median duration of therapy. The
      patients were examined for factors associated with steatosis and treatment
      efficacy according to the grade of steatosis. Early viral kinetics was also
      evaluated in 64 patients for predictors of response to therapy. Nine IFN
      resistant patients were assessed for the relationship between amino acid sequence
      of HCV core region/NS5A and severity of steatosis. Multivariate analysis
      identified two independent factors associated with steatosis; serum ferritin > or
      =200 microg/l and body mass index > or =25.0 kg/m(2). The sustained virological
      response rate in patients with high-grade steatosis was significantly lower than
      in the low-grade group. Study of early viral kinetics showed a significantly
      lower cumulative HCV-RNA negative rate for the high-grade than low-grade
      steatosis group. Sequence analysis of HCV core region/NS5A in IFN-resistant
      patients with or without steatosis failed to identify steatosis-specific amino
      acid substitutions associated with resistance. This study of HCV genotype 2a
      suggested that steatosis is associated with excess iron storage, and that it is
      an important predictor of efficacy of IFN monotherapy. Further large-scale
      studies are warranted to examine the role of amino acid substitutions on IFN
      resistance specific for steatosis.

PMID- 15714493
TI  - Detection and genotyping of human papillomavirus in cervical samples from Italian
      patients.
AB  - Human papillomaviruses (HPVs) are etiological agents of cervical cancer. In order
      to assess the epidemiological incidence and frequency of different HPV types, we
      applied a polymerase chain reaction (PCR)-direct sequencing approach based on the
      use of MY09/MY11 primers as compared to Hybrid Capture assay. Cervical samples
      were taken from 1,500 women, both with normal and abnormal cytological smears,
      and we found an incidence of 6.6% of HPV infection in Brescia. Overall, 97
      samples tested HPV-positive, yielding 18 HPV types. The four most frequent HPV
      types were: HPV 16, -31, -6, and -58. This approach could be used in ordinary
      laboratory settings for quick and reliable typing of known and novel HPVs from
      clinical specimens and it could also be applied to anti-cancer vaccine
      development.

PMID- 15714494
TI  - Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu
      speaking sub-saharan Africans.
AB  - Genotypes A, D, and E of the hepatitis B virus (HBV) circulate in southern
      Africa, with genotype A predominating. Their hepatocarcinogenic potential in
      Bantu-speaking sub-saharan Africans is, however, unknown. Using a case/control
      format, we investigated the hepatocarcinogenic potential of these genotypes and
      subgenotype A1 of genotype A, which accounts for the great majority of genotype A
      isolates. HBV isolates from 111 unselected Bantu-speaking sub-saharan Africans
      with hepatocellular carcinoma (HCC) and 111 matched asymptomatic chronic
      carriers, serving as controls, were genotyped using the method of [Lindh et al.
      (1997): J Infect Dis 175:1285-1293]. Subgenotypes of genotype A were determined
      using an in-house restriction fragment length polymorphism assay. Genotype A was
      present in 96 (86.5%) of patients with HCC and 76 (68.5%) of the carriers, giving
      a 4.5-fold (95% confidence limits: 1.86, 10.90) increased risk of HCC in carriers
      infected with genotype A compared with those infected with non-A genotypes. HCC
      patients infected with genotype A were significantly younger than those infected
      with non-A genotypes (P = 0.02). The distributions between these two groups
      according to sex, geographic background, and tribe were not significantly
      different. Subgenotype A1 was present in all of the 77 cancer patients and 69 of
      70 carriers analyzed, yielding a relative risk of 4.21 (95% confidence limits:
      1.73,10.23) of HCC in those infected with subgenotype A1 compared with those
      infected with non-A genotypes. Genotype A has a greater hepatocarcinogenic
      potential than non-A genotypes in Bantu-speaking sub-saharan Africans and this is
      entirely attributable to subgenotype A1.

PMID- 15714496
TI  - Surface modification of poly(ether urethane urea) with modified
      dehydroepiandrosterone for improved in vivo biostability.
AB  - In this study, a fatty acid urethane derivative of dehydroepiandrosterone (DHEA)
      was synthesized and evaluated as a polyurethane additive to increase long-term
      biostability. The modification was hypothesized to reduce the water solubility of
      the DHEA and physically anchor the additive in the polyurethane during
      implantation. Polyurethane film weight loss in water as a function of time was
      studied to determine the polymer retention of the modified DHEA. The polyurethane
      film with unmodified DHEA had significant weight loss in the first day (10%) that
      was previously correlated to rapid leaching of the additive. The polyurethane
      film with modified DHEA had significantly less weight loss at all time points
      indicating improved polymer retention. The effect of the modified DHEA additive
      on the biostability of a poly(ether urethane urea) was examined after 5 weeks of
      subcutaneous implantation in Sprague-Dawley rats. Optical micrographs and
      infrared analysis of the specimens indicated that the modified DHEA bloomed to
      the surface of the film forming a crystalline surface layer approximately 10-15
      microns thick. After explantation, this surface layer was intact without
      measurable differences in surface chemistry as monitored by attenuated total
      reflectance-Fourier transform infrared spectroscopy. There was no evidence of
      degradation of the polyurethane underneath the modified DHEA surface layer as
      compared with the polyurethane control. We have concluded that the modified DHEA
      self-assembled into a protective surface coating that inhibited degradation of
      the polyurethane. The roughness of the modified DHEA surface layer prevented
      adherent cell analysis to determine if the additive retained the ability to down
      regulate macrophage activity. Subsequent studies will investigate the ability of
      surface-modifying additives to modulate cellular respiratory bursts in addition
      to the formation of an impermeable barrier. This bimodal approach to improving
      biostability holds great promise in the field of polyurethane biomaterials.

PMID- 15714495
TI  - Genetic heterogeneity of the NS3 protease gene in hepatitis C virus genotype 1
      from untreated infected patients.
AB  - NS3 protease is essential for hepatitis C Virus (HCV) replication, and is one of
      the most promising targets for specific anti-HCV therapy. Its natural
      polymorphism has not been studied at the quasispecies level. In the present work,
      the genetic heterogeneity of the NS3 protease gene was analyzed in 17 HCV
      genotype 1 (5 subtypes 1a and 12 subtypes 1b) samples collected from infected
      patients before anti-viral therapy. A total of 294 clones were sequenced.
      Although the protease NS3 is considered to be one of the less variable genes in
      the HCV genome, variability of both nucleotide and amino acid sequences was
      found. In variants belonging to 1a and 1b subtypes, 224 and 267 of 543 positions
      showed one or more nucleotide substitutions, respectively. Forty and 74 of the
      181 NS3 amino acid positions showed at least one mutation in HCV-1a and HCV-1b
      isolates, respectively. Most substitutions were conservative. This substantial
      polymorphism of the NS3 protease produced by HCV-1a and HCV-1b suggests that,
      despite the numerous functional and structural constraints, the enzyme is
      sufficiently flexible to tolerate substitutions.

PMID- 15714497
TI  - Rhinovirus infects primary human airway fibroblasts and induces a neutrophil
      chemokine and a permeability factor.
AB  - The events linking rhinovirus (RV) infection to airway symptoms are poorly
      understood. The virus initially infects airway epithelium followed by a vigorous
      inflammatory response that may entail spread of RV from epithelium to other cells
      in the airway wall. However, RV has fastidious growth characteristics and to date
      reproductive infection of primary cells other than human airway epithelium has
      not been confirmed. Airway fibroblasts are adjacent to and in contact with
      epithelial cells, play a key role in innate immune responses, and may participate
      in the evolution of inflammation. To investigate fibroblast actions, we first
      determined whether RV could infect and replicate in primary culture human lung
      fibroblasts. RV serotype 16 (RV16) was used to infect fibroblasts grown from lung
      tissue, and virus infection with replication was demonstrated by a combination of
      techniques. RT-PCR was used to show an increase in RV transcription; confocal
      microscopy demonstrated colocalization of the replicative form of RV genome
      (double-stranded RNA) and RV16 proteins; infectious virus was also recovered from
      the culture supernatant of infected fibroblasts. Functional consequences of RV
      infection were next examined. RV infection of fibroblasts was followed by an
      increase in epithelial neutrophil-activating peptide-78 (ENA-78) mRNA and
      protein. The permeability factor vascular endothelial growth factor (VEGF) was
      also induced over a similar time course. These data suggest that interactions
      between RV and human fibroblasts are feasible, may coordinate neutrophil
      chemoattraction with enhanced vascular permeability and that fibroblasts may
      contribute to inflammatory responses following RV infections.

PMID- 15714498
TI  - Gene expression in tissue associated with extracellular matrix modified ePTFE.
AB  - Previous studies have established that surface modification of ePTFE with
      extracellular matrix molecules promotes vascularization within and around the
      implanted material. To understand the molecular basis of this tissue response to
      modified ePTFE, we analyzed large-scale gene expression in nonmodified and
      extracellular matrix-modified ePTFE-associated healing. Using a microarray
      containing 15,000 unique mouse cDNAs and an ANOVA-based analysis, we identified
      789 genes related to cell signaling, inflammation, matrix remodeling, and
      proliferation that were differentially expressed across time, between
      modifications, or both. Genes were clustered based upon similarity in gene
      expression, producing 7 unique temporal super-patterns of expression. The
      clustered data revealed 3 general expression patterns unique to tissue
      surrounding the nonmodified ePTFE, while 6 unique expression patterns were
      associated with extracellular matrix-modified ePTFE. The more diverse expression
      patterns associated with extracellular matrix-modified ePTFE suggests that the
      tissue surrounding the extracellular matrix-modified ePTFE is more dynamic in
      terms of transcriptional activity. Taken together, these clusters serve as a
      "genetic fingerprint" for tissue healing in response to a specific material or
      material modification. Use of these genetic profiles will aid in the pursuit of
      improved device biocompatibility and enhanced material function.

PMID- 15714499
TI  - Mechano-active scaffold design of small-diameter artificial graft made of
      electrospun segmented polyurethane fabrics.
AB  - To fabricate a "mechano-active" tubular scaffold of nonwoven mesh-type small
      diameter artificial graft made of the synthetic durable elastomer, segmented
      polyurethane, the fabrication technique of electrospinning on a mandrel under a
      high rotation speed and transverse movement was used. Emphasis was placed on how
      the rotation speed of the mandrel and the fusion or welding states of fibers at
      contact points affect the compliance (ease of intraluminal pressure-dependent
      circumferential inflation) and Young's modulus determined by uniaxial stretching
      in the longitudinal and circumferential directions. The results showed that a
      high rotation speed is attributed to exhibit isotropic mechanical properties in
      the entire range of applied strain but reduces the compliance, and a high fusion
      state, which is produced using a mixed solvent with a high content of high
      boiling-point solvent, reduces the compliance but is expected to exhibit high
      durability in a continuously loaded pulsatile stress field in an arterial
      circulatory system.

PMID- 15714500
TI  - Osteogenic potential of injectable tissue-engineered bone: a comparison among
      autogenous bone, bone substitute (Bio-oss), platelet-rich plasma, and tissue
      engineered bone with respect to their mechanical properties and histological
      findings.
AB  - Recently, tissue engineering has become available as a regenerative treatment for
      bone defects. However, the evaluation of its success is limited to histological
      analysis, and its effects on mechanical hardness remain to be investigated. This
      study investigated mechanical strength in support of histological findings,
      specifically for tissue-engineered bone with mesenchymal stem cells (MSCs) and
      platelet-rich-plasma (PRP). Initially, teeth were extracted, and bone defects on
      both sides of the mandible were prepared with a trephine bar. The defects were
      implanted by using the following graft materials: 1) PRP, 2) PRP and dog MSCs
      (dMSCs), 3) autogenous bone (PCBM), 4) bone substitute (Bio-Oss), and 5) control
      (defects only). After 2, 4, 8, and 12 weeks of implantation, the defects were
      histologically assessed to examine their mechanical properties. According to
      histological observations, the dMSCs/PRP groups had well-formed mature bone
      compared with the control (defects only), Bio-Oss, and PRP groups. The Vickers
      hardness test values were 8 (control), 9 (PRP), not detected (Bio-Oss), 11
      (PCBM), and 17 (dMSCs/PRP) after 2 weeks. Therefore, tissue-engineered bone can
      be used for early stage bone regeneration from the viewpoint of histology and
      mechanical properties.

PMID- 15714501
TI  - A computational approach to predicting cell growth on polymeric biomaterials.
AB  - A predictive model that can correlate the chemical composition of a biomaterial
      with the biological response of cells that are in contact with that biomaterial
      would represent a major advance and would facilitate the rational design of new
      biomaterials. As a first step toward this goal, we report here on the use of
      Logical Analysis of Data (LAD) to model the effect of selected polymer properties
      on the growth of two different cell types, rat lung fibroblasts (RLF, a
      transformed cell line), and normal foreskin fibroblasts (NFF, nontransformed
      human cells), on 112 surfaces obtained from a combinatorially designed library of
      polymers. LAD is a knowledge extraction methodology, based on using
      combinatorics, optimization, and Boolean logic. LAD was trained on a subset of 62
      polymers and was then used to predict cell growth on 50 previously untested
      polymers. Experimental validation indicated that LAD correctly predicted the high
      and low cell growth polymers and found optimal ranges for polymer chemical
      composition, surface chemistry, and bulk properties. Particularly noteworthy is
      that LAD correctly identified high-performing polymer surfaces, which surpassed
      commercial tissue culture polystyrene as growth substratum for normal foreskin
      fibroblasts. Our results establish the feasibility of using computational
      modeling of cell growth on flat polymeric surfaces to identify promising "lead"
      polymers for applications that require either high or low cell growth.

PMID- 15714502
TI  - Flow cytometric measurement of phagocytosis reveals a role for C3b in metal
      particle uptake by phagocytes.
AB  - A methodology for the quick and efficient study of phagocytosis has been
      developed. It uses the flow cytometer to exploit the change in size and
      granularity that occurs in cells upon the ingestion of particulate material. The
      numbers of cells that have phagocytosed particles can be calculated from the
      distinct shift in regions that occurs. The method also allows the factors
      governing phagocytosis to be studied in detail through the use of blocking agents
      or antibodies. Blood-derived monocytes were studied to investigate the role of
      complement in metal particle phagocytosis to further understand aseptic
      loosening. Factor C3b was found to be fundamental to the opsonization and
      phagocytosis of metal particles by monocytes.

PMID- 15714504
TI  - Effect of particulate bioactive glasses on human macrophages and monocytes in
      vitro.
AB  - Bioactive glasses, originally developed to promote tissue adhesion, are finding
      an increasing array of biomedical applications. The aim of the current study was
      to assess the ability of silicate- and zinc phosphate-based bioactive glasses to
      modulate the secretion of cytokines from activated human macrophages and
      monocytes. Human macrophages and monocytes were isolated and cultured on surfaces
      coated with a range of quantities of the bioactive glasses. Nontoxic
      concentrations of the glasses were selected and assessed further for their
      ability to modulate the secretion of tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-10 and -6, in the presence or absence of the stimulant
      lipopolysaccharide. 45S5 glass produced a significant reduction to the amount of
      TNF-alpha (p<0.05) and IL-6 (p<0.01) secreted by stimulated cells compared with
      cells stimulated in the absence of bioactive glass. A significant reduction in IL
      6 secretion was also observed with the other silicate- and zinc phosphate-based
      glasses tested. IL-10 secretion was increased (but not significantly) in presence
      of all glasses tested. TNF-alpha and IL-6 secretion from stimulated cells was
      lower in presence of the silicate glasses compared with the zinc phosphate
      glasses, indicating that this system of bioactive glass might be of clinical use
      in conditions associated with inflammation.

PMID- 15714503
TI  - Interactions of dopamine D1 and D2 receptor antagonists with D-methamphetamine
      induced hyperthermia and striatal dopamine and serotonin reductions.
AB  - The effects of the dopamine D1 receptor antagonist R(+)-SCH-23390 and D2 receptor
      antagonist S(-)-eticlopride on d-methamphetamine-induced striatal monoamine
      reductions 72 h after treatment were investigated in relation to changes in body
      temperature. Rats were administered four 10-mg/kg doses of d-methamphetamine or
      saline with a 2-h interval between treatments; 0.5 mg/kg eticlopride or SCH-23390
      was administered 15 min before each methamphetamine or saline injection. Two
      ambient temperature conditions were investigated: 24 and 33 degrees C.
      Methamphetamine administered at 24 degrees C induced hyperthermia and reduced
      striatal dopamine content by 73%; 0.5 mg/kg eticlopride or SCH-23390 administered
      in combination with methamphetamine at 24 degrees C attenuated methamphetamine
      induced hyperthermia and prevented significant reductions in dopamine content. At
      33 degrees C, eticlopride and SCH-23390 were ineffective in blocking
      methamphetamine-induced hyperthermia and dopamine content was reduced by 65% in
      the SCH-23390-methamphetamine group. By contrast, dopamine content was reduced by
      only 31% in the 33 degrees C eticlopride-methamphetamine group. Thus, although
      the eticlopride-methamphetamine treatment combination at 33 degrees C exhibited a
      hyperthermic response comparable to that seen with methamphetamine alone at 24
      degrees C, reductions in dopamine content were attenuated in the combination
      group compared with methamphetamine alone at 24 degrees C. Serotonin changes
      showed similar attenuated reductions after SCH-23390 or eticlopride pretreatment
      at 24 degrees C in combination with methamphetamine, but this attenuation was
      absent at 33 degrees C. The dissociation of methamphetamine-induced striatal
      dopamine reduction and hyperthermia seen after eticlopride pretreatment suggests
      a dopamine D2 receptor mechanism in mediating methamphetamine-induced dopamine
      depletion. However this D2 mechanism does not apply to methamphetamine-induced
      striatal serotonin reductions.

PMID- 15714505
TI  - Adsorption of serum fetuin to hydroxylapatite does not contribute to osteoblast
      phenotype modifications.
AB  - Osteoblasts exhibit enhanced differentiation and altered gene profiles when
      cultured on hydroxyapatite (HA) compared to plastic surfaces. To begin
      determining mechanisms for this response, we used proteomics to identify proteins
      predominantly found in osteoblasts on HA but not plastic surfaces. Two
      dimensional gel electrophoresis and Western analyses indicate that fetuin is
      abundant in extracts from HA, but not plastic surfaces. Incubation of HA and
      plastic surfaces with cell culture medium (containing 10% serum) under cell-free
      conditions shows that fetuin is predominantly derived from the culture medium
      serum and readily adsorbs to the HA surface. However, we did detect low levels of
      fetuin B mRNA in osteoblasts. Serum albumin, actin-beta, apolipoprotein-AI, and
      vimentin also adsorbed to HA. To determine the role of fetuin in the HA-induced
      osteoblast phenotype changes, osteoblasts were seeded onto fetuin-coated or
      uncoated HA under serum-free conditions. Osteoblast morphology was similar on
      both HA surfaces, suggesting that HA alone (without adsorbed serum proteins) is
      sufficient for cell attachment and spreading. Similarly, genes previously
      reported to be modulated by HA (glvr-1, DMP-1, osteoglycin, and proliferin 3)
      were modulated even in the absence of fetuin or other serum proteins. These data
      show that HA surface can be enriched selectively with fetuin from serum; however,
      neither fetuin or other serum proteins are required to mediate HA-induced
      osteoblast attachment, spreading, or changes in expression of genes examined.
      This finding suggests that factors intrinsic to HA are required for the response.

PMID- 15714507
TI  - Biocompatibility of titanium implants modified by microarc oxidation and
      hydroxyapatite coating.
AB  - A thin hydroxyapatite (HA) layer was coated on a microarc oxidized titanium (MAO
      Ti) substrate by means of the sol-gel method. The microarc oxidation (anodizing)
      enhanced the biocompatibility of the Ti, and the bioactivity was improved further
      by the sol-gel HA coating on the anodized Ti. The HA sol was aged fully to obtain
      a stable and phase-pure HA, and the sol concentration was varied to alter the
      coating thickness. Through the sol-gel HA coating, the Ca and P concentrations in
      the coating layer increased significantly. However, the porous morphology and
      roughness of the MAO-Ti was altered very little by the sol-gel treatment. The
      proliferation and alkaline phosphatase (ALP) activity of the osteoblast-like
      cells on the MAO/HA sol-gel-treated Ti were significantly higher than those on
      the MAO-Ti without the HA sol-gel treatment.

PMID- 15714506
TI  - Role of phosphorylated CaMKII and calcineurin in the differential effect of
      hypothyroidism on LTP of CA1 and dentate gyrus.
AB  - Hypothyroidism impairs early long-term potentiation (LTP) in the CA1 but not in
      the dentate gyrus (DG) of hippocampus of anesthetized adult rats. Protein levels
      and activities of signaling molecules in both the CA1 and DG of surgically
      thyroidectomized and sham-operated euthyroid rats were measured. Basal levels of
      total calmodulin kinase II (CaMKII) protein in both the CA1 and DG were decreased
      in hypothyroidism. Marked reduction of basal P-CaMKII levels and CaMKII activity
      was seen in CA1, but not in the DG of the same hypothyroid animals. Basal levels
      of calmodulin and protein kinase Cgamma (PKCgamma) were decreased in CA1 but
      remained unchanged in the DG of hypothyroid rats. Basal calcineurin levels and
      activity, although enhanced in CA1, were reduced in the DG of hypothyroid rats.
      These findings suggest that the DG may possess a compensatory mechanism whereby
      calcineurin levels are reduced, to allow sufficient CaMKII activity to produce an
      apparently normal LTP in hypothyroid rats.

PMID- 15714508
TI  - Preparation and characterization of novel tricalcium silicate bioceramics.
AB  - Novel tricalcium silicate (Ca3SiO5) ceramics were successfully fabricated. The
      mechanical properties of the ceramics were dependent remarkably on sintering
      temperature. The fracture toughness, Young's modules, and bending strength of
      Ca3SiO5 ceramics sintered at 1500 degrees C were 1.93 MPa . m1/2, 36.7 GPa, and
      93.4 MPa, respectively. These findings suggest that the Ca3SiO5 ceramics possess
      good mechanical properties, and might be a potential bone implant material.

PMID- 15714509
TI  - Language processing within the human medial temporal lobe.
AB  - Although the hippocampal formation is essential for verbal memory, it is not
      fully understood how it contributes to language comprehension. We recorded event
      related potentials (ERPs) directly from two substructures of the medial temporal
      lobe (MTL), the rhinal cortex and the hippocampus proper, while epilepsy patients
      listened to sentences that either were correct or contained semantic or syntactic
      violations. Semantic violations elicited a large negative ERP response peaking at
      approximately 400 ms in the rhinal cortex. In contrast, syntactically incorrect
      sentences elicited a negative deflection of 500-800 ms in the hippocampus proper.
      The results suggest that functionally distinct aspects of integration in language
      comprehension are supported by different MTL structures: the rhinal cortex is
      involved in semantic integration, whereas the hippocampus proper subserves
      processes of syntactic integration. An analysis of phase synchronization within
      the gamma band between rhinal and hippocampal recording sites showed that both of
      the above-mentioned ERP components were preceded by an increase of phase
      synchronization. In contrast to these short phasic increases of phase
      synchronization in both violation conditions, correct sentences were associated
      with a long-lasting synchronization in a late time window, possibly reflecting
      the integration of semantic and syntactic information as required for normal
      comprehension.

PMID- 15714510
TI  - Pathophysiology of spastic paresis. I: Paresis and soft tissue changes.
AB  - Spastic paresis follows chronic disruption of the central execution of volitional
      command. Motor function in patients with spastic paresis is subjected over time
      to three fundamental insults, of which the last two are avoidable: (1) the neural
      insult itself, which causes paresis, i.e., reduced voluntary motor unit
      recruitment; (2) the relative immobilization of the paretic body part, commonly
      imposed by the current care environment, which causes adaptive shortening of the
      muscles left in a shortened position and joint contracture; and (3) the chronic
      disuse of the paretic body part, which is typically self-imposed in most
      patients. Chronic disuse causes plastic rearrangements in the higher centers that
      further reduce the ability to voluntarily recruit motor units, i.e., that
      aggravate baseline paresis. Part I of this review focuses on the pathophysiology
      of the first two factors causing motor impairment in spastic paresis: the vicious
      cycle of paresis-disuse-paresis and the contracture in soft tissues.

PMID- 15714511
TI  - Pathophysiology of spastic paresis. II: Emergence of muscle overactivity.
AB  - In the subacute and chronic stages of spastic paresis, stretch-sensitive
      (spastic) muscle overactivity emerges as a third fundamental mechanism of motor
      impairment, along with paresis and soft tissue contracture. Part II of this
      review primarily addresses the pathophysiology of the various forms of spastic
      overactivity. It is argued that muscle contracture is one of the factors that
      cause excessive responsiveness to stretch, which in turn aggravates contracture.
      Excessive responsiveness to stretch also impedes voluntary motor neuron
      recruitment, a concept termed stretch-sensitive paresis. None of the three
      mechanisms of impairment (paresis, contracture, and spastic overactivity) is
      symmetrically distributed between agonists and antagonists, which generates
      torque imbalance around joints and limb deformities. Thus, each may be best
      treated focally on an individual muscle-by-muscle basis. Intensive motor training
      of the less overactive muscles should disrupt the cycle of paresis-disuse
      paresis, and concomitant use of aggressive stretch and focal weakening agents in
      their more overactive and shortened antagonists should break the cycle of
      overactivity-contracture-overactivity.

PMID- 15714512
TI  - Temporalis function in anthropoids and strepsirrhines: an EMG study.
AB  - The major purpose of this study is to analyze anterior and posterior temporalis
      muscle force recruitment and firing patterns in various anthropoid and
      strepsirrhine primates. There are two specific goals for this project. First, we
      test the hypothesis that in addition to transversely directed muscle force, the
      evolution of symphyseal fusion in primates may also be linked to vertically
      directed balancing-side muscle force during chewing (Hylander et al. [2000] Am.
      J. Phys. Anthropol. 112:469-492). Second, we test the hypothesis of whether
      strepsirrhines retain the hypothesized primitive mammalian condition for the
      firing of the anterior temporalis, whereas anthropoids have the derived condition
      (Weijs [1994] Biomechanics of Feeding in Vertebrates; Berlin: Springer-Verlag, p.
      282-320). Electromyographic (EMG) activities of the left and right anterior and
      posterior temporalis muscles were recorded and analyzed in baboons, macaques, owl
      monkeys, thick-tailed galagos, and ring-tailed lemurs. In addition, as we used
      the working-side superficial masseter as a reference muscle, we also recorded and
      analyzed EMG activity of the left and right superficial masseter in these
      primates. The data for the anterior temporalis provided no support for the
      hypothesis that symphyseal fusion in primates is linked to vertically directed
      jaw muscle forces during mastication. Thus, symphyseal fusion in primates is most
      likely mainly linked to the timing and recruitment of transversely directed
      forces from the balancing-side deep masseter (Hylander et al. [2000] Am. J. Phys.
      Anthropol. 112:469-492). In addition, our data demonstrate that the firing
      patterns for the working- and balancing-side anterior temporalis muscles are near
      identical in both strepsirrhines and anthropoids. Their working- and balancing
      side anterior temporalis muscles fire asynchronously and reach peak activity
      during the power stroke. Similarly, their working- and balancing-side posterior
      temporalis muscles also fire asynchronously and reach peak activity during the
      power stroke. Compared to these strepsirrhines, however, the balancing-side
      posterior temporalis of anthropoids appears to have a relatively delayed firing
      pattern. Moreover, based on their smaller W/B ratios, anthropoids demonstrate a
      relative increase in muscle-force recruitment of the balancing-side posterior
      temporalis. This in turn suggests that anthropoids may emphasize the duration and
      magnitude of the power stroke during mastication. This hypothesis, however,
      requires additional testing. Furthermore, during the latter portion of the power
      stroke, the late activity of the balancing-side posterior temporalis of
      anthropoids apparently assists the balancing-side deep masseter in driving the
      working-side molars through the terminal portion of occlusion.

PMID- 15714513
TI  - African ancestry of the population of Buenos Aires.
AB  - The population of Argentina today does not have a "visible" black African
      component. However, censuses conducted during most of the 19th century registered
      up to 30% of individuals of African origin living in Buenos Aires city. What has
      happened to this African influence? Have all individuals of African origin died,
      as lay people believe? Or is it possible that admixture with the European
      immigrants made the African influence "invisible?" We investigated the African
      contribution to the genetic pool of the population of Buenos Aires, Argentina,
      typing 12 unlinked autosomal DNA markers in a sample of 90 individuals. The
      results of this analysis suggest that 2.2% (SEM=0.9%) of the genetic ancestry of
      the Buenos Aires population is derived from Africa. Our analysis of individual
      admixture shows that those alleles that have a high frequency in populations of
      African origin tend to concentrate among 8 individuals in our sample. Therefore,
      although the admixture estimate is relatively low, the actual proportion of
      individuals with at least some African influence is approximately 10%. The
      evidence we are presenting of African ancestry is consistent with the known
      historical events that led to the drastic reduction of the Afro-Argentine
      population during the second half of the 19th century. However, as our results
      suggest, this reduction did not mean a total disappearance of African genes from
      the genetic pool of the Buenos Aires population.

PMID- 15714514
TI  - Long-term survival of ancient DNA in Egypt: response to Zink and Nerlich (2003).

PMID- 15714516
TI  - How pathogenic is the p.D104N/endostatin polymorphic allele of COL18A1 in
      Knobloch syndrome?

PMID- 15714518
TI  - Late onset N-acetylglutamate synthase deficiency caused by hypomorphic alleles.
AB  - N-acetylglutamate (NAG) is a unique cofactor that is essential for the conversion
      of ammonia to urea in the liver. N-acetylglutamate synthase (NAGS) catalyzes the
      formation of NAG. Deficiency of NAGS causes a block in ureagenesis resulting in
      hyperammonemia. Although a number of mutations have been identified in the NAGS
      gene, their effects on NAGS enzymatic activity have not been examined. We
      describe here three mutations in two families with NAGS deficiency. Studies of
      the purified recombinant mutant proteins revealed deleterious effects on NAGS
      affinity for substrates, and on the rate of catalysis. These studies provide a
      better understanding of the function of NAGS, and the mechanisms for deleterious
      effect of mutations causing inherited NAGS deficiency.

PMID- 15714519
TI  - Validation of dye-binding/high-resolution thermal denaturation for the
      identification of mutations in the SLC22A5 gene.
AB  - Primary carnitine deficiency is an autosomal recessive disorder of fatty acid
      oxidation resulting from defective carnitine transport. This disease is caused by
      mutations in the OCTN2 carnitine transporter encoded by the SLC22A5 gene. Here we
      validate dye-binding/high-resolution thermal denaturation as a screening
      procedure to identify novel mutations in this gene. This procedure is based on
      the amplification of DNA by PCR in capillaries with the dsDNA binding dye LCGreen
      I. The PCR reaction is then analyzed in the same capillary by high-resolution
      thermal denaturation. Samples with abnormal melting profiles are sequenced. This
      technique correctly identified all known patients who were compound heterozygotes
      for different mutations in the carnitine transporter gene and about 30% of
      homozygous patients. The remaining 70% of homozygous patients were identified by
      a second amplification, in which the patient's DNA was mixed with the DNA of a
      normal control. This screening system correctly identified eight novel mutations
      and both abnormal alleles in six new families with primary carnitine deficiency.
      The causative role of the missense mutations identified (c.3G>T/p.M1I,
      c.695C>T/p.T232M, and c.1403 C>G/p.T468R) was confirmed by expression in Chinese
      hamster ovary (CHO) cells. These results expand the mutational spectrum in
      primary carnitine deficiency and indicate dye-binding/high-resolution thermal
      denaturation as an ideal system to screen for mutations in diseases with no
      prevalent molecular alteration.

PMID- 15714520
TI  - Genetic association of the APP binding protein 2 gene (APBB2) with late onset
      Alzheimer disease.
AB  - Alzheimer disease (AD) is a complex neurodegenerative disorder predisposed by
      multiple genetic factors. Mutations in amyloid beta precursor protein (APP) are
      known to be associated with autosomal dominant, early onset familial AD and
      possibly also late onset AD (LOAD). A number of genes encoding proteins capable
      of binding to APP have been identified, but their contribution to AD pathobiology
      remains unclear. Conceivably, mutations in these genes may play a role in
      affecting AD susceptibility, which appears to be substantiated by some genetic
      studies. Here we report results of the first genetic association study with
      APBB2, an APP binding protein (also known as FE65L), and LOAD, in three
      independently collected case-control series totaling approximately 2,000 samples.
      Two SNPs were significantly associated with LOAD in two sample series and in meta
      analyses of all three sample sets (for rs13133980: odds ratio [OR](hom)=1.36 [95%
      CI: 1.05-1.75], OR(het)=1.32 [95% CI: 1.04-1.67], minor allele frequency=43%,
      P=0.041; and for hCV1558625: OR(hom)=1.37 [95% CI: 1.06-1.77], OR(het)=1.02 [95%
      CI: 0.82-1.26], minor allele frequency=48%, P=0.026). One of these SNPs, located
      in a region conserved between the human and mouse genome, showed a significant
      interaction with age of disease onset. For this marker, the association with LOAD
      was most pronounced in subjects with disease onset before 75 years of age
      (OR(hom)=2.43 [95% CI: 1.61-3.67]; OR(het)=2.15 [95% CI: 1.46-3.17]; P=0.00006)
      in the combined sample set. Our data raise the possibility that genetic
      variations in APBB2 may affect LOAD susceptibility.

PMID- 15714521
TI  - Role of beta-galactosidase and elastin binding protein in lysosomal and
      nonlysosomal complexes of patients with GM1-gangliosidosis.
AB  - G(M1)-gangliosidosis is a lysosomal storage disorder caused by a deficiency of
      beta-galactosidase (GLB1). The GLB1 gene gives rise to the GLB1 lysosomal enzyme
      and to the elastin binding protein (EBP), involved in elastic fiber deposition.
      GLB1 forms a complex with protective protein cathepsin A (PPCA), alpha
      neuraminidase (NEU1), and galactosamine 6-sulphate sulfatase (GALNS) inside
      lysosomes, while EBP binds to PPCA and NEU1 on the cell surface. We investigated
      the function of the GLB1 and EBP mutated proteins by analyzing the clinical,
      genetic, and cellular data of 11 G(M1)-gangliosidosis patients. Their molecular
      analysis, followed by expression studies, lead to the identification of four new
      and 10 known GLB1 mutations. Some common amino acid substitutions [c.1445G>A
      (p.Arg482H), c.622C>T (p.Arg208His), c.175C>T (p.Arg59Cys) and c.176G>A
      (p.Arg59His)] were present in the GLB1 enzyme of several patients, all of
      Mediterranean origin, suggesting a common origin. Western blotting analyses
      against GLB1, EBP, and PPCA proteins showed that the identified mutations affect
      GLB1 enzyme activity and/or stability. The c.1445G>A (p.Arg482His), c.175C>T
      (p.Arg59Cys), c.733+2T>C, c.1736G>A (p.Gly579Asp), and c.1051C>T (p.Arg351X) GLB1
      mutations, affect the stabilization of PPCA probably because they hamper the
      interaction between GLB1/EBP and PPCA within the multiprotein complex. The amount
      of EBP was normal, but the detection of impaired elastogenesis in such patients
      suggests an alteration in its function. We conclude that the presence of genetic
      lesions in both GLB1 and EBP coding region does not directly predict impaired
      elastogenesis and that elastic fiber assembly has to be evaluated specifically in
      each case. Nevertheless, the degree of EBP involvement may be linked to specific
      clinical findings.

PMID- 15714522
TI  - cblE type of homocystinuria due to methionine synthase reductase deficiency:
      functional correction by minigene expression.
AB  - The cblE type of homocystinuria is a rare autosomal recessive disorder caused by
      impaired reductive activation of methionine synthase. Although earlier
      biochemical studies proposed that the methionine synthase enzyme might be
      activated by two different reducing systems, mutations were reported in only the
      methionine synthase reductase gene (MTRR) in cblE patients. The pathogenicity of
      MTRR mutations, however, has not yet been tested functionally. We report on nine
      patients of European origin affected by the cblE type of homocystinuria. They
      presented between 2 weeks and 3 years of age (median age 4 weeks) with anemia,
      which was macrocytic in only three patients, and with neurological involvement in
      all but two cases. Bone marrow examination performed in seven patients showed
      megaloblastic changes in all but one of them. All patients exhibited moderate to
      severe hyperhomocysteinemia (median plasma total homocysteine [Hcy] 92 mumol/L,
      range 44-169), while clearly reduced methionine was observed only in four cases.
      Pathogenic mutations were identified in both parental alleles of the MTRR gene in
      all patients. Five known (c.903+469T>C, c.1361C>T, c.1459G>A, c.1557
      4_1557+3del7, and c.1622_1623dupTA) and three novel mutations (c.7A>T, c.1573C>T,
      and c.1953-6_1953-2del5) were detected. Importantly, transfection of fibroblasts
      of cblE patients with a wild-type MTRR minigene expression construct resulted in
      a significant approximately four-fold increase of methionine synthesis,
      indicating correction of the enzyme defect. Our study shows a link between a
      milder predominantly hematological presentation and homozygosity for the
      c.1361C>T mutation, but no other obvious genotype-phenotype correlation. The
      identification of mutations in the MTRR gene, together with restoration of
      methionine synthesis following MTRR minigene expression in cblE cells confirms
      that this disease is caused by defects in the MTRR gene.

PMID- 15714525
TI  - Research trends in human osteology: a content analysis of papers published in the
      American Journal of Physical Anthropology.
AB  - This paper explores recent research trends in human osteology, based on articles
      published in the American Journal of Physical Anthropology (AJPA) during two 5
      year intervals: 1980--1984 and 1996--2000. Topical "visibility" is measured in
      terms of article counts; "impact" is estimated through citation indices. Our
      results indicate that human osteologists continue to publish a range of
      methodological, analytical, and descriptive research papers that address a broad
      array of subjects. Analytical articles are cited more frequently than descriptive
      articles and thus have higher impact, reflecting the discipline's continued
      commitment to problem-oriented research. Differences in publication patterns
      exist between scholars during early and later stages of their careers. Articles
      published by students and Ph.D.s within 2 years of their doctoral degree are more
      frequently descriptive than analytical, when compared to people with longer
      career histories. Topics such as pathology, forensic anthropology, and
      biodistance modeling remain highly visible, while articles on the dentition have
      waned. An increase in functional research directed toward the postcranial
      skeleton is also reflected in our data. While continued visibility for
      morphological investigations is apparent, the impact of recently developed
      applications in bone chemistry and molecular anthropology is amply documented in
      our data, particularly during the more recent survey years.

PMID- 15714523
TI  - Single nucleotide polymorphisms in the MATP gene are associated with normal human
      pigmentation variation.
AB  - Human physical pigmentation is determined by the type and amount of melanin and
      the process of pigmentation production probably involves more than 100 genes. A
      failure to synthesize melanin results in oculocutaneous albinism (OCA). A
      recently identified form of OCA results from mutations in the Membrane Associated
      Transporter Protein (MATP) gene. The role of MATP in human pigmentation is not
      clear. We investigated the role of two nonpathogenic nonsynonymous single
      nucleotide polymorphisms (SNPs) in the MATP gene to determine if they are
      associated with normal human skin, hair, and eye color variation. A total of 608
      individuals from four different population groups (456 Caucasians, 31 Asians, 70
      African-Americans, and 51 Australian Aborigines) were genotyped for c.814G>A
      (p.Glu272Lys) and c.1122C>G (p.Phe374Leu). Results indicate that the allele
      frequencies of both polymorphisms are significantly different between population
      groups. The two alleles, 374Leu and 272Lys, are significantly associated with
      dark hair, skin, and eye color in Caucasians. The odds ratios (ORs) of the LeuLeu
      genotype for black hair and olive skin are 25.63 and 28.65, respectively, and for
      the LysLys genotype are 43.23 and 8.27, respectively. The OR for eye color is
      lower at 3.48 for the LeuLeu and 6.57 for LysLys genotypes. This is the first
      report of this highly significant association of MATP polymorphisms with normal
      human pigmentation variation.

PMID- 15714526
TI  - Synthesis and structure of an unexpected platinum pi complex formed from
      substituted 1,4-diamino ligands through an elimination process.
AB  - An unusual reactivity of cis-1,2-bis[(N,N-dimethylamino)methyl] cyclohexane with
      PtCl(2) was observed, resulting in the formation of a platinum(II) pi-olefin
      complex instead of the conventional square-planar cis Pt(II) coordination complex
      with the diamino ligand. This behavior was interpreted on the basis of the steric
      hindrance of the dimethylamino groups whose electron lone pairs are barely
      accessible to a platinum atom, which can make it difficult for both dimethylamino
      groups to bind platinum at the same time. This complex has been physically and
      spectroscopically characterized and its structure has been confirmed by using X
      ray diffraction analyses on single crystals.

PMID- 15714529
TI  - Betaine-induced assembly of neutral infinite columns and chains of linked
      silver(I) polyhedra with embedded acetylenediide.
AB  - Ten polymeric silver(I) double salts containing embedded acetylenediide:
      [(Ag2C2)2(AgCF3CO2)9(L1)3] (1), [(Ag2C2)2(AgCF3CO2)10(L2)3]H2O (2),
      [(Ag2C2)(AgCF3CO2)4(L3)(H2O)]0.75 H2O (3), [(Ag2C2)(1.5)(AgCF3CO2)7(L4)2] (4),
      [(Ag2C2)(AgCF3CO2)7(L5)2(H2O)] (5), [(Ag2C2) (AgC2F5CO2)7(L1)3(H2O)] (6),
      [(Ag2C2)(AgCF3CO2)7(L1)3(H2O)]2 H2O (7), [(Ag2C2)(AgC2F5CO2)6(L3)2] (8),
      [(Ag2C2)2(AgC2F5CO2)12(L4)2(H2O)4]H2O (9), and [(Ag2C2)(AgCF3CO2)6(L3)2(H2O)]H2O
      (10) have been isolated by varying the types of betaines, the
      perfluorocarboxylate ligands employed, and the reaction conditions. Single
      crystal X-ray analysis has shown that 1-4 all have a columnar structure composed
      of fused silver(I) double cages, with C2(2-) species embedded in its stem and an
      exterior coat comprising anionic and zwitterionic carboxylates. For 5 and 6,
      single silver(I) cages are linked into a beaded chain through both types of
      carboxylate ligands. In 7, two different coordination modes of L1 connect the
      silver(I) polyhedra into a chain. For 8, the mu(2)-O,O' coordination mode of L3
      connects the silver(I) double cages into a chain. Compound 9 exhibits a two
      dimensional architecture generated from the cross-linkage of double cages by
      C2F5CO2-, L4, and [Ag2(C2F5CO2)2] units. Similar to 9, 10 is also a two
      dimensional structure, which is formed by connecting the chains of linked double
      cages through [Ag2(CF3CO2)2] bridging.

PMID- 15714528
TI  - Enantioselective syntheses and configuration assignments of gamma-chiral
      butenolides from Plagiomnium undulatum: butenolide synthesis from tetronic acids.
AB  - Both enantiomers of the gamma-chiral alpha,beta-dimethylated butyrolactones nat-1
      and nat-2 from the moss Plagiomnium undulatum were synthesized stereoselectively
      through butenolides and tetronic acids, respectively. The configuration of the
      natural products was determined by GLC comparisons with mono(3-O-acetyl-6-O-tert
      butyldimethylsilyl-2-O-methyl)hexakis(6-O-tert-butyldimethylsilyl-2,3-di-O
      methyl)-beta-cyclodextrin as a stationary phase.

PMID- 15714530
TI  - One-dimensional polymers based on [{CpMo(CO)2}2(mu,eta2-P2)]: solid-state
      conformation analysis by NMR spectroscopy and DFT calculations.
AB  - Reaction of the complex [{CpMo(CO)2}2(mu,eta2-P2)] (1) with CuI halides leads to
      the quantitative formation of the novel one-dimensional linear polymers
      [CuX{Cp2Mo2(CO)4(mu,eta2:eta1:eta1-P2)}](infinity) (X=Cl (4), Br (5), I (6)). The
      same products 4 and 5 were obtained when 1 was treated with CuCl2 and CuBr2,
      respectively. The solid-state structures are compared and their remarkable
      influence on the respective (31)P magic angle spinning (MAS) NMR spectra is
      interpreted with the help of density functional theory (DFT) calculations on the
      model compounds [{(CuX)2{Cp2Cr2(CO)4(mu,eta(2):eta1:eta1-P2)}2}3] (X=Cl (4 a), Br
      (5 a)) in which the molybdenum atoms are replaced by their lighter homologue
      chromium.

PMID- 15714532
TI  - Soluble oligoaramide precursors--a novel class of building blocks for rod-coil
      architectures.
AB  - A new synthetic route is described that allows the reversible conversion of the
      inherently insoluble oligo-p-benzamides into soluble materials through the
      formation of imidoyl chlorides. Syntheses of the corresponding dimer, trimer, and
      tetramer are reported; these compounds can easily be purified by crystallization
      and are accessible on the multigram scale. Structural proof was obtained by
      single-crystal X-ray structures of the trimer and tetramer precursors. They can
      be selectively functionalized into amides or esters at the terminal carboxylic
      acid group followed by hydrolysis of the imidoyl chlorides to the parent amides.
      This new class of compounds gives access to strongly aggregating rigid rodlike
      materials in few synthetic steps, as is demonstrated by the preparation of
      poly(ethylene glycol)-co-oligo(p-benzamide) rod-coil block copolymers.

PMID- 15714531
TI  - pentafluorophenyl-phenyl interactions in biphenyl-DNA.
AB  - We prepared and investigated oligonucleotide duplexes of the sequence
      d(GATGAC(X)nGCTAG).d(CTAGC(Y)nGTCATC), in which X and Y designate biphenyl- (bph)
      and pentafluorobiphenyl- ((5F)bph) C-nucleotides, respectively, and n varies from
      0-4. These hydrophobic base substitutes are expected to adopt a zipperlike,
      interstrand stacking motif, in which not only bph/bph or (5F)bph/(5F)bph homo
      pairs, but also (5F)bph/bph mixed pairs can be formed. By performing UV-melting
      curve analysis we found that incorporation of a single (5F)bph/(5F)bph pair leads
      to a duplex that is essentially as stable as the unmodified duplex (n=0), and 2.4
      K more stable than the duplex with the nonfluorinated bph/bph pair. The T(m) of
      the mixed bph/(5F)bph pair was in between the T(m) values of the respective homo
      pairs. Additional, unnatural aromatic pairs increased the T(m) by +3.0-4.4
      K/couple, irrespective of the nature of the aromatic residue. A thermodynamic
      analysis using isothermal titration calorimetry (ITC) of a series of duplexes
      with n=3 revealed lower (less negative) duplex formation enthalpies (DeltaH) in
      the (5F)bph/(5F)bph case than in the bph/bph case, and confirmed the higher
      thermodynamic stability (DeltaG) of the fluorinated duplex, suggesting it to be
      of entropic origin. Our data are compatible with a model in which the stacking of
      (5F)bph versus bph is dominated by dehydration of the aromatic units upon duplex
      formation. They do not support a model in which van der Waals dispersive forces
      (induced dipoles) or electrostatic (quadrupole) interactions play a dominant
      role.

PMID- 15714533
TI  - Titanium imido complexes of cyclooctatetraenyl ligands.
AB  - Reaction of [Ti(NR)Cl2(py)3] (R=tBu or 2,6-iPr2C6H3) with K(2)[COT] (COT=C8H8) or
      Li2[COT''] (COT''=1,4-C8H6(SiMe3)2) gave the monomeric complexes [Ti(NR)(eta8
      COT)] or [Ti(NR)(eta8-COT'')], respectively. The pseudo-two coordinate, "pogo
      stick" geometry for these complexes is unique in both early transition-metal and
      cyclooctatetraenyl ligand chemistry. In contrast, reaction of [Ti(N-2,6
      Me2C6H3)Cl2(py)3] with K2[COT] gave the mu-imido-bridged dimer [Ti2(mu-N-2,6
      Me2C6H3)2(eta8-COT)2]. It appears that as the steric bulk of the imido and C8
      ring substituents are decreased, dimerisation becomes more favourable. Aryl imido
      COT complexes were also prepared by imido ligand exchange reactions between
      anilines and [Ti(NtBu)(eta(8)-COT)] or [Ti(NtBu)(eta(8)-COT'')]. The complexes
      [Ti(NtBu)(eta(8)-COT)], [Ti(N-2,6-iPr2C6H3)2(eta8-COT)] and [Ti2(mu-N-2,6
      Me2C6H3)2(eta8-COT)2] have been crystallographically characterised. The
      electronic structures of both the monomeric and dimeric complexes have been
      investigated by using density functional theory (DFT) calculations and gas-phase
      photoelectron spectroscopy. The most striking aspect of the bonding is that
      binding to the imido nitrogen atom is primarily through sigma and pi
      interactions, whereas that to the COT or COT'' ring is almost exclusively through
      delta symmetry orbitals. A DFT-based comparison between the bonding in
      [Ti(NtBu)(eta8-COT)] and the bonding in the previously reported late transition
      metal "pogo stick"complexes [Os(NtBu)(eta6-C6Me6)], [Ir(NtBu)(eta5-C5Me5)] and
      [Ni(NO)(eta5-C5H5)] has also been undertaken.

PMID- 15714534
TI  - Nonenzymatic glucose detection by using a three-dimensionally ordered,
      macroporous platinum template.
AB  - A three-dimensionally ordered, macroporous, inverse-opal platinum film was
      synthesized electrochemically by the inverted colloidal-crystal template
      technique. The inverse-opal film that contains platinum nanoparticles showed
      improved electrocatalytic activity toward glucose oxidation with respect to the
      directly deposited platinum; this improvement is due to the interconnected porous
      structure and the greatly enhanced effective surface area. In addition, the
      inverse-opal Pt-film electrode responds more sensitively to glucose than to
      common interfering species of ascorbic acid, uric acid, and p-acetamidophenol due
      to their different electrochemical reaction mechanisms. Results showed that the
      ordered macroporous materials with enhanced selectivity and sensitivity are
      promising for fabrication of nonenzymatic glucose biosensors.

PMID- 15714535
TI  - Acidity trends in alpha,beta-unsaturated sulfur, selenium, and tellurium
      derivatives: comparison with C-, Si-, Ge-, Sn-, N-, P-, As-, and Sb-containing
      analogues.
AB  - The gas-phase acidity of CH3-CH2XH (X=S, Se, Te), CH2=CHXH (X=S, Se, Te) and PhXH
      (X=S, Se) compounds was measured by means of Fourier transform ion cyclotron
      resonance mass spectrometry. To analyze the role that unsaturation plays on the
      intrinsic acidity of these systems, a parallel theoretical study, in the
      framework of the G2 and the G2(MP2) theories, was carried out for all ethyl,
      ethenyl (vinyl), ethynyl, and phenyl O-, S-, Se-, and Te-containing derivatives.
      Unsaturated compounds are stronger acids than their saturated analogues, because
      of the strong pi-electron donor ability of the heteroatoms that contributes to a
      large stabilization of the unsaturated anions. Ethynyl derivatives are stronger
      acids than vinyl compounds, while phenyl derivatives have an intrinsic acidity
      intermediate between that of the corresponding vinyl and ethynyl analogues. The
      CH2=CHXH vinyl compounds (enol-like) behave systematically as slightly stronger
      acids than their CH3-C(H)X (keto-like) tautomers. Vinyl derivatives are stronger
      acids than ethyl compounds, because the anion stabilization attributable to
      unsaturation is greater than that undergone in the neutral compounds. Conversely,
      the enhanced acidity of the ethynyl derivatives with respect to the vinyl
      compounds is due to two concomitant effects, the stabilization of the anion and
      the destabilization of the neutral compound. The acidities of ethyl, vinyl, and
      ethynyl derivatives containing heteroatoms of Groups 14, 15, and 16 of the
      periodic table are closely related, and reflect the differences in
      electronegativity of the CH3CH2-, CH2=CH-, and CH[triple chemical bond]C- groups.

PMID- 15714536
TI  - Benzoyl transfer reactivities of racemic 2,4-di-O-acyl-myo-inosityl 1,3,5
      orthoesters in the solid state: molecular packing and intermolecular interactions
      correlate with the ease of the reaction.
AB  - Racemic 2,4-di-O-acyl-myo-inosityl 1,3,5-orthoesters undergo transesterification
      catalyzed by sodium carbonate with varying ease of reaction in the solid state;
      reactions in solution and melt do not show such varied differences. An
      interesting crystal of a 1:1 molecular complex of highly reactive racemic 2,4-di
      O-benzoyl-myo-inosityl 1,3,5-orthoformate and its orthoacetate analogue exhibited
      better reactivity than the latter component alone. Single-crystal X-ray
      structures of the reactants have been correlated with the observed differences in
      the acyl-transfer efficiencies in the solid state. Although each of the
      derivatives helically self-assembles around the crystallographic 2(1) axis linked
      through O-H...O hydrogen bonding, the pre-organization of the reactive groups
      (C=O [El] and OH [Nu]), C-H...O and the C-H...pi interactions are significantly
      more favourable for the reactive derivatives than the less reactive ones. Bond
      length distributions also showed differences; the O-C bond of the axial benzoyl
      group, which gets cleaved during the reaction, is longer (1.345-1.361 A) relative
      to the chemically equivalent O-C bond of the equatorial benzoyl group (1.316
      1.344 A) in the reactive derivatives. These bond-length differences are not
      significant in the less reactive derivatives. The overall molecular organization
      is different too; the strikingly discrete helices, which may be viewed as
      "reaction tunnels" and are held by interhelical interactions, are clearly evident
      in the reactive derivatives in comparison with the less reactive ones.

PMID- 15714537
TI  - Mild and efficient copper-catalyzed cyanation of aryl iodides and bromides.
AB  - An efficient copper-catalyzed cyanation of aryl iodides and bromides is reported.
      Our system combines catalytic amounts of both copper salts and chelating ligands.
      The latter, which have potential nitrogen- and/or oxygen-binding sites, have
      never previously been used in this type of reaction. A protocol has been
      developed that enables the cyanation of aryl bromides through the copper
      catalyzed in situ production of the corresponding aryl iodides using catalytic
      amounts of potassium iodide. Aryl nitriles are obtained in good yields and
      excellent selectivities in relatively mild conditions (110 degrees C) compared
      with the Rosenmund-von Braun cyanation reaction. Furthermore, the reaction is
      compatible with a wide range of functional groups including nitro and amino
      substituents. The protocol reported herein involves two main innovations: the use
      of catalytic amounts of ligands and the use of acetone cyanohydrin as the
      cyanating agent in copper-mediated cyanation reactions.

PMID- 15714538
TI  - Crystal structures, anisotropic growth, and optical properties: controlled
      synthesis of lanthanide orthophosphate one-dimensional nanomaterials.
AB  - The fundamental understanding of the relationship between crystal structure and
      the dynamic processes of anisotropic growth on the nanoscale, and exploration of
      the key factors governing the evolution of physical properties in functional
      nanomaterials, have become two of the most urgent and challenging issues in the
      fabrication and exploitation of functional nanomaterials with designed properties
      and the development of nanoscale devices. Herein, we show how structural and
      kinetic factors govern the tendency for anisotropic growth of such materials
      under hydrothermal conditions, and how the crystal structure and morphology
      influence the optical properties of Ln3+-doped nanocrystals. The synthesis of
      phase-pure and single-crystalline monoclinic, hexagonal, and tetragonal one
      dimensional LnPO4 nanostructures of different aspect ratios by means of
      kinetically controlled hydrothermal growth processes is demonstrated. It is shown
      that the tendency for anisotropic growth under hydrothermal conditions can be
      enhanced simply by modifying the chemical potentials of species in the reaction
      solution through the use of carefully selected chelating ligands. A systematic
      study of the photoluminescence of various Eu3+-doped lanthanide phosphates has
      revealed that the optical properties of these nanophosphors are strongly
      dependent on their crystal structures and morphologies.

PMID- 15714539
TI  - Pseudorotation barriers of biological oxyphosphoranes: a challenge for
      simulations of ribozyme catalysis.
AB  - Pseudorotation reactions of biologically relevant oxyphosphoranes were studied by
      using density functional and continuum solvation methods. A series of 16
      pseudorotation reactions involving acyclic and cyclic oxyphosphoranes in neutral
      and monoanionic (singly deprotonated) forms were studied, in addition to
      pseudorotation of PF5. The effect of solvent was treated by using three different
      solvation models for comparison. The barriers to pseudorotation ranged from 1.5
      to 8.1 kcal mol(-1) and were influenced systematically by charge state,
      apicophilicity of ligands, intramolecular hydrogen bonding, cyclic structure and
      solvation. Barriers to pseudorotation for monoanionic phosphoranes occur with the
      anionic oxo ligand as the pivotal atom, and are generally lower than for neutral
      phosphoranes. The OCH3 groups were observed to be more apicophilic than OH
      groups, and hence pseudorotations that involve axial OCH3/equatorial OH exchange
      had higher reaction and activation free energy values. Solvent generally lowered
      barriers relative to the gas-phase reactions. These results, together with
      isotope 18O exchange experiments, support the assertion that dianionic
      phosphoranes are not sufficiently long-lived to undergo pseudorotation.
      Comparison of the density functional results with those from several
      semiempirical quantum models highlight a challenge for new-generation hybrid
      quantum mechanical/molecular mechanical potentials for non-enzymatic and
      enzymatic phosphoryl transfer reactions: the reliable modeling of pseudorotation
      processes.

PMID- 15714540
TI  - Combining solid-phase microextraction and on-line preconcentration-capillary
      electrophoresis for sensitive analysis of pesticides in foods.
AB  - The combined use of solid-phase microextraction (SPME) and different on-line
      preconcentration strategies for ultrasensitive capillary electrophoresis
      ultraviolet (CE-UV) analysis of five pesticides in a single run is investigated.
      Normal stacking mode (NSM), field-enhanced sample injection (FESI), and stacking
      with matrix removal (SWMR) are explored to increase the sensitivity of the CE-UV
      analysis of a selected group of pesticides (cyprodinil, cyromazine, pyrifenox,
      pirimicarb, and pyrimethanil). It could be observed that reverse polarity
      stacking with matrix removal (RP-SWMR) provided the best results in terms of
      sensitivity (enhancement was up to 272-fold compared with normal injection). The
      separation buffer consisted of 0.4 mM cetyltrimethylammonium chloride (CTAC), 0.4
      M acetic acid at pH 4 containing 5% v / v 2-propanol. This approach was then
      combined with SPME to determine the pesticides in water, apple, and orange juice.
      The combination of both preconcentration procedures allowed the determination of
      these pesticides at concentrations down to 2.5 microg / L in water and 3.1 microg
      / L in juices (i.e., levels well below the maximum residue limits allowed for
      these compounds). To our knowledge, this is the first report showing the great
      possibilities of the combined use of SPME, on-line sample preconcentration, and
      CE for pesticide analysis.

PMID- 15714541
TI  - On-column capillary electrophoretic monitoring of rapid reaction kinetics for
      determination of the antioxidative potential of various bioactive phenols.
AB  - An on-column capillary electrophoretic procedure for the determination of the
      antioxidative potential of various bioactive phenols, found in plant, fruit, and
      vegetable extracts, is described. The assay is based on a rapid mixing of phenols
      or phenolic extracts before the capillary, followed by pressurized injection of
      the reaction mixture into the capillary. After incubation of the reaction mixture
      inside the capillary, high voltage is switched on and separation of reactants and
      products is performed. Using hydrogen peroxide as a stressor, the kinetics of the
      oxidation of various bioactive phenols was studied (rutin, chlorogenic acid,
      quercetin, caffeic acid, gallic acid, and combinations of these) and compared
      with the oxidation rate of L-ascorbic acid as a reference. The concept was
      demonstrated for the determination of the antioxidative potential of various
      polyphenol mixtures and of the methanol extract of the sea buckthorn (Hippophae
      rhamnoides L.). In most cases quercetin has the highest rate constant of
      oxidation among the tested phenolic compounds. However, in the mixture L-ascorbic
      acid/quercetin, the oxidation rate of L-ascorbic acid was enhanced and oxidation
      of quercetin was strongly inhibited compared with the other combinations of
      tested polyphenols.

PMID- 15714543
TI  - Separation and on-column preconcentration of some nonsteroidal anti-inflammatory
      drugs by microemulsion electrokinetic capillary chromatography using high-speed
      separations.
AB  - Various strategies have been investigated for separating a group of nonsteroidal
      anti-inflammatory drugs (NSAIDs) by microemulsion electrokinetic capillary
      chromatography (MEEKC) using high-speed separations. The parameters that of
      affect the separation, such as the nature of the oil droplet and the buffer, and
      the surfactant concentration have been studied. In addition, several organic
      solvents were used to decrease the retention of the analytes in the oil droplet
      phase and to improve the resolution of the NSAIDs. The optimum microemulsion
      background electrolyte (BGE) solution made of 0.8% w/w ethyl acetate, 6.6% w/w
      butan-1-ol, 6.0% w/w acetonitrile, 1.0% w/w sodium dodecyl sulfate (SDS), and
      85.6% w/w of 10 mM sodium tetraborate at pH 9.2 resolved the drugs within 8 min.
      The short-end injection procedure is an alternative for reducing the analysis
      time. When this procedure was used, the microemulsion BGE solution consisted of
      0.8% w/w ethyl acetate, 6.6% w/w butan-1-ol, 17.0% w/w methanol, 1.0% w/w SDS,
      and 74.6% w/w of 10 mM sodium tetraborate, pH 9.2, and the NSAIDs were separated
      within 3 min. The reversed electrode polarity stacking mode (REPSM) technique was
      applied to the on-line concentration of the NSAIDs. In this technique, the sample
      matrix was pumped out of the capillary using a polarity-switching step. When this
      technique was applied, the sensitivity was enhanced up to 40-fold and the limits
      of detection (LODs) were in the low microg.L(-1) levels.

PMID- 15714544
TI  - Micellar electrokinetic chromatography of bilirubin, related compounds, and
      selected drugs with mixtures of binary bile salts.
AB  - Micellar electrokinetic chromatography was used to study the behavior of quinine,
      propranolol, bilirubin, biliverdin dimethyl ester, and xanthobilirubin methyl
      ester in single and binary bile salt micelle systems comprised of glycocholic
      acid and glycodeoxycholic acid. Micelle systems studied had total bile salt
      concentrations in the range of 10-33 mM with molar ratios of 1:0, 2:1, 1:1, 1:2,
      and 0:1 glycocholic acid:glycodeoxycholic acid. A pH 8.5 phosphate-borate buffer
      system was used. For all analytes except bilirubin, the smallest migration
      factors were found in glycocholic acid solutions and the largest in
      glycodeoxycholic acid solutions. Intermediate migration factors were found for
      all compounds except bilirubin in the binary bile salt systems. Bilirubin behaved
      uniquely with its largest migration factors in the binary bile salt mixtures.

PMID- 15714542
TI  - Rapid assessment of beta-asarone content of Acorus calamus by micellar
      electrokinetic capillary chromatography.
AB  - This report outlines a rapid, reproducible method for the determination of beta
      asarone, a known carcinogen, using micellar electrokinetic capillary
      chromatography (MEKC)-UV-vis absorbance and a simple alcohol extraction. The MEKC
      method is based on a running buffer comprised of 100 mM sodium dodecyl sulfate
      (SDS), pH 10. The method is reproducible and provides baseline separation of
      alpha-asarone and beta-asarone. This protocol was used to determine the beta
      asarone content of Acorus calamus rhizome of a diploid variety harvested from the
      wetlands of the United States and the triploid variety from India obtained
      commercially. The results indicate raw product that originated from India
      contained 4.4% w/w beta-asarone, while that from the United States contained 0.2%
      w/w beta-asarone. Neither sample contained detectable concentrations of alpha
      asarone. This is the first report of the use of MEKC to determine asarone in a
      natural source.

PMID- 15714545
TI  - Determination of ceftazidime in plasma and cerebrospinal fluid by micellar
      electrokinetic chromatography with direct sample injection.
AB  - A simple micellar electrokinetic chromatography (MEKC) with UV detection at 254
      nm for analysis of ceftazidime in plasma and in cerebrospinal fluid (CSF) by
      direct injection without any sample pretreatment is described. The separation of
      ceftazidime from biological matrix was performed at 25 degrees C using a
      background electrolyte consisting of Tris buffer with sodium dodecyl sulfate
      (SDS) as the electrolyte solution. Under optimal MEKC condition, good separation
      with high efficiency and short analyses time is achieved. Several parameters
      affecting the separation of the drug from biological matrix were studied,
      including pH and concentration of the Tris buffer and SDS. Using cefazolin as an
      internal standard (IS), the linear ranges of the method for the determination of
      ceftazidime in plasma and in CSF were all over the range of 3-90 microg/mL; the
      detection limit of the drug in plasma and in CSF (signal-to-noise ratio = 3;
      injection 0.5 psi, 5 s) was 2.0 microg/mL. The applicability of the proposed
      method for determination of ceftazidime in plasma and CSF collected after
      intravenous administration of 2 g ceftazidime in patients with meningitis was
      demonstrated.

PMID- 15714546
TI  - Separation and determination of L-tryptophan and its metabolites by capillary
      micellar electrokinetic chromatography with amperometric detection.
AB  - A high-performance method of capillary micellar electrokinetic chromatography
      (CMEKC) with amperometric detection (AD), using a newly designed pre-aligned
      electrochemical cell, has been developed for the separation and determination of
      L-tryptophan (Trp) and its eight metabolites including 3-hydroxy-L-kynurenine (3
      HK), 5-hydroxy-L-tryptophan (5-HTP), L-kynurenine (KN), 5-hydroxyindole-3-acetic
      acid (5-HIAA), xanthurenic acid (XA), indole-3-pyruvic acid (IPA), 5
      hydroxytryptamine (5-HT), and tryptamine (Tryp). A carbon disk electrode was used
      as the working electrode and the optimal detection potential was 0.85 V (versus
      Ag/AgCl). At 24 kV of applied voltage, the nine compounds were completely
      separated, within 23 min, in a 10 mol/L Na(2)HPO(4)-NaOH buffer (pH 11.0)
      containing 40 mmol/L sodium dodecyl sulfate (SDS) and 3% methanol (v/v). A good
      linear relationship was obtained for all analytes in this paper and the detection
      limits of 3-HK, 5-HTP, KN, Trp, 5-HIAA, XA, IPA, 5-HT, and Tryp were 7.42, 5.18,
      34.6, 3.99, 15.1, 12.7, 260, 6.72, and 8.01 nmol/L, respectively. This method has
      been applied to analyze the metabolism of Trp in rabbit urine.

PMID- 15714547
TI  - Amino acid analysis by micellar electrokinetic chromatography with laser-induced
      fluorescence detection: application to nanolitre-volume biological samples from
      Arabidopsis thaliana and Myzus persicae.
AB  - Amino acids were derivatised with 4-fluoro-7-nitrobenzo-2,1,3-oxadiazol (NBD-F),
      separated by micellar electrokinetic chromatography (MEKC), and detected by argon
      ion (488 nm) laser-induced fluorescence. The optimised MEKC background
      electrolyte conditions were: 40 mM sodium cholate, 5 mM beta-cyclodextrin in 20
      mM aqueous borate buffer, pH 9.1, with 7% v/v acetonitrile. Using these
      conditions, 19 amino acids were separated within 17 min. The limits of detection
      were in the range of 7.6-42.2 pmol/mL and limits of quantitation from 0.05-0.14
      nmol/mL. The method was systematically validated for injection volume error,
      migration time variation, calibration linearity, accuracy, precision, and
      recovery. Nanolitre volume samples of phloem sap of individual sieve element
      cells from the plant Arabidopsis thaliana and honeydew from the aphid Myzus
      persicae were directly analysed with this method. Quantitative amino acid
      concentrations in these two biological matrices were profiled for the first time.
      This method is particularly important because it allows the complete profile of
      the amino acids obtained from individual phloem elements, allowing cell to cell
      and plant to plant variation to be quantified, which to date has not been
      possible with Arabidopsis thaliana.

PMID- 15714548
TI  - Analysis of anticancer platinum(II)-complexes by microemulsion electrokinetic
      chromatography: separation of diastereomers and estimation of octanol-water
      partition coefficients.
AB  - Microemulsion electrokinetic chromatography (MEEKC) was applied for the
      separation and lipophilicity estimation of oxaliplatin and eight novel anticancer
      oxaliplatin derivatives. Solubility and permeability have to be balanced in
      modern drug development, and the octanol-water partition coefficient (log P)
      still represents one of the most useful quantifiable parameters providing a
      reasonable estimation of a drug's lipophilicity. Therefore, the capacity factors
      from MEEKC were correlated to log P values derived by the traditional shake flask
      method. The MEEKC method was accomplished using a microemulsion of heptane/sodium
      dodecyl sulfate (SDS)/butanol in phosphate buffer at pH 7.4 and 37 degrees C with
      all analytes being in a neutral state during the run. This experimental setup
      allowed a baseline separation of all platinum complexes within 11 min.
      Remarkably, beside the very good resolution and precision of the measurements,
      separation of diastereomers of the complexes and quantification of the
      diastereomeric ratios could be achieved. Correlating the capacity factors with
      the corresponding log P values resulted in a linear dependency with a correlation
      factor of r = 0.9935. Consequently, the applied MEEKC method was found to be a
      highly valuable technique not only for the separation of platinum complexes but
      as well for the estimation of the octanol-water partition coefficient with many
      advantages in comparison to other methods.

PMID- 15714549
TI  - Comparison of microemulsion electrokinetic chromatography and micellar
      electrokinetic chromatography as methods for the analysis of ten benzophenones.
AB  - Microemulsion electrokinetic chromatography (MEEKC) and micellar electrokinetic
      chromatograpy (MEKC) were compared for their abilities to separate and detect ten
      similar benzophenones, which are commonly used as UV filters in various plastic
      and cosmetic products. Sodium dodecyl sulfate (SDS) concentration and column
      temperature rarely affected separation resolution for MEEKC, but separation of
      benzophenones could be improved by changing the SDS concentration and column
      temperature for MEKC. Buffer pH and ethanol (organic modifier) were found to
      markedly influence the separation selectivity for both MEEKC and MEKC systems. In
      addition, a higher electric voltage improved the separation efficiency without a
      noticeable reduction in separation resolution for MEEKC, whereas it caused a poor
      separation resolution for the MEKC system.

PMID- 15714550
TI  - Micellar proportion: a parameter to compare the hydrophobicity of the
      pseudostationary phases or that of the analytes in micellar electrokinetic
      chromatography.
AB  - Micellar proportion, t(prop,mic) = t(mic)/t(m), a quantity expressing how much
      time is spent by the analyte in the micellar phase related to its whole migration
      time (t(m)) has been introduced by utilizing the micellar phase residence time
      (t(mic)). The t(prop,mic) values have been determined for analytes of different
      chemical structures (alkyl benzene and alkyl phenone homologous series, alcohols,
      strongly hydrophobic peptides) studied by micellar elektrokinetic chromatography
      (MEKC) using various cationic and anionic pseudostationary phases. A good linear
      correlation was obtained between t(prop,mic) and the calculated hydrophobicity
      (CLOGP) of the analytes for all pseudostationary phases (CLOGP = A.logt(prop,mic)
      + B). Considering a given pseudostationary phase, t(prop,mic) as a relative
      quantity is a suitable parameter to characterize and compare experimentally the
      behavior of the various analytes in MEKC. Applying a set of probe molecules with
      known hydrophobicity, the CLOGP(50) value (showing the value of hydrophobicity of
      a virtual molecule spending exactly 50% of its migration time in the
      pseudostationary phase) has been calculated for each pseudostationary phase
      applied here. This experimentally determinable numerical value (characterizing
      the pseudostationary phase) can be utilized to compare the hydrophobicity and
      hence retention ability of the pseudostationary phases. The t(prop,mic) value was
      found to be applicable to compare the methylene selectivity of the different
      pseudostationary phases as well: logt(prop,mic) = A.Z + B, where Z is the number
      of carbon atoms of the alkyl chain in the alkyl benzene homologous series.

PMID- 15714551
TI  - Electrokinetic capillary chromatography in a polar continuous-phase water-in-oil
      microemulsion constituted by water, sodium dodecyl sulfate, and n-pentanol.
AB  - A water-in-oil (w/o) microemulsion (ME) constituted by 15% Tris buffer, pH 8.4,
      in water and 85% sodium dodecyl sulfate (SDS)/n-pentanol 1:4 mixture, capable of
      dissolving up to 30% vegetable oils and lard, was used as background electrolyte
      in reverse microemulsion electrokinetic capillary chromatography (RMEEKC). Owing
      to the free SDS ions in the continuous phase and some degree of percolation, the
      ME showed a high conductivity (0.65 mS. cm(-1) at 25 degrees C) and sustained a
      very stable capillary current. Previous rinsing of the capillary with a
      quaternary ammonium salt for electroosmotic flow (EOF) reduction, a series of
      nonionic and anionic solutes dissolved either in the ME or in fat samples diluted
      with the ME (1:4 ratio), were injected. Using -20 kV, fair separations of the
      solutes in the migration time order singly charged anions < nonionic solutes <
      doubly charged anions approximately pyromellitate were obtained, salicylate (I)
      showing by far the shortest migration time, and phthalate (II) and pyromellitate
      the longest. Separation was attributed to partition between the aqueous droplets,
      where pyromellitate and II were assumed to be trapped, and the n-pentanol
      continuous phase, where the mobilitites could be also modified by association of
      the solutes with SDS ions. Adequate EOF markers were not found, thus the relative
      mobility of any solute with respect to the mobility of the droplets, mu(r), was
      expressed as a fraction of the mobility of I with respect to that of the
      droplets, being mu(r) = (t(II) - t(R)) t(I) / [(t(II) - t(I)) t(R)], where t(R),
      t(I), and t(II) are the migration times of the solutes I and II, respectively.
      The application of RMEEKC to the analysis of both hydrophilic and hydrophobic
      samples, including edible fats, was demonstrated.

PMID- 15714552
TI  - Post-translational modifications influence transcription factor activity: a view
      from the ETS superfamily.
AB  - Transcription factors provide nodes of information integration by serving as
      nuclear effectors of multiple signaling cascades, and thus elaborate layers of
      regulation, often involving post-translational modifications, modulating and
      coordinate activities. Such modifications can rapidly and reversibly regulate
      virtually all transcription factor functions, including subcellular localization,
      stability, interactions with cofactors, other post-translational modifications
      and transcriptional activities. Aside from analyses of the effects of
      serine/threonine phosphorylation, studies on post-translational modifications of
      transcription factors are only in the initial stages. In particular, the
      regulatory possibilities afforded by combinatorial usage of and competition
      between distinct modifications on an individual protein are immense, and with
      respect to large families of closely related transcription factors, offer the
      potential of conferring critical specificity. Here we will review the post
      translational modifications known to regulate ETS transcriptional effectors and
      will discuss specific examples of how such modifications influence their
      activities to highlight emerging paradigms in transcriptional regulation.

PMID- 15714553
TI  - Magnesium: The missing element in molecular views of cell proliferation control.
AB  - The quantitative study of regulation of cell growth and proliferation began with
      the development of the technique for monolayer culture of vertebrate cells in the
      late 1960s. The basic parameters were defined in the early physiological studies,
      which continued through the next decade. These included specific and non-specific
      growth factors and the requirement for continuous exposure to such factors
      through most of the G1 period for progression to S. In the course of this work,
      the diversity of biochemical responses and the critical role of increased protein
      synthesis and accumulation for the onset of DNA synthesis were elucidated. In
      particular, a central role of free cytosolic Mg2+ in direct regulation of protein
      synthesis and in ancillary processes as a response to membrane perturbation was
      established. Eventually, the physiological era was superseded by the molecular
      era beginning in the 1980s. This work focussed on specific receptors for growth
      factors that entrained a protein kinase cascade, which terminated in a higher
      frequency of initiation of protein synthesis. However, the molecular studies
      virtually ignored the key results of the physiological era. Recent studies of the
      penultimate molecular steps in the regulatory pathway of protein synthesis,
      however, have supported a model of growth regulation involving membrane
      perturbation and MgATP2- concentration, results that integrate the findings of
      the physiological and molecular eras. The resulting relatively simple "membrane,
      magnesium mitosis" (MMM) model of proliferation control can explain the seeming
      paradox of the variety of specific and non-specific growth-enhancing treatments
      that are mediated by the plasma membrane and which bring about a shared, complex
      but coordinated growth response that drives cell proliferation.

PMID- 15714554
TI  - Shuttling between species for pathways of lifespan regulation: a central role for
      the vitellogenin gene family?
AB  - Studies to find genes that affect maximum lifespan aim at identifying important
      determinants of ageing that may be universal across species. Model organisms show
      insulin signalling can play an important role in ageing. In view of insulin
      resistance, such loci can also be important in human ageing and health. The study
      of long-lived humans and their children points to the relevance of lipoprotein
      profiles and particle size for longevity. If ageing pathways are conserved, then
      the genes mediating such pathways may also be conserved. Cross-species sequence
      comparisons of potential longevity loci may reveal whether the pathways that they
      represent are central themes in lifespan regulation. Using bioinformatic tools,
      we performed a sequence comparison of the genes involved in lipid metabolism
      identified in humans as potential longevity loci. This analysis revealed that
      lipid storage and transport may be a common theme related to longevity in humans,
      honeybees and nematodes. Here, the vitellogenin family emerges as a potential key
      connection between lipid metabolism and the insulin/IGF-1 signalling pathway.

PMID- 15714555
TI  - Why cavefish are blind.
AB  - Some fish exist as eyed, surface-dwelling and eyeless, cave-dwelling forms. The
      developmental processes that cause eye degeneration in different populations of
      Astyanax cavefish are similar. Although small optic primordia start to form,
      apoptosis of lens cells triggers developmental arrest and degeneration of the
      eyes. Degeneration has been linked to reduced expression of the transcription
      factor Pax6 in the anterior embryonic midline and optic primordia. Recently,
      Yamamoto and colleagues reported that increased expression of the diffusible
      morphogen Sonic hedgehog (Shh) at the embryonic midline of cavefish reduces pax6
      expression and increases expression of Shh-regulated genes, which might confer
      selective advantages for life in caves.

PMID- 15714556
TI  - The remote roots of consciousness in fruit-fly selective attention?
AB  - A mechanistic study of consciousness need not be confined to human complexity.
      Other animals also display key behaviors and responses that have long been
      intimately tied to the measure of consciousness in humans. Among them are some
      very well-defined and measurable endpoints: selective attention, sleep and
      general anesthesia. That these three variables associated with changes in
      consciousness might exist even in a fruit-fly does not necessarily imply that a
      fly is "conscious", but it does suggest that some of the problems central to the
      field of consciousness studies could be investigated in a model organism such as
      Drosophila melanogaster. Demonstrating suppression of unattended stimuli, which
      is central to attention studies in humans, is now possible in Drosophila by
      measuring neural correlates of visual selection. By combining such studies with
      an eventual understanding of suppression in other arousal states in the fly, such
      as sleep and general anesthesia, we might be unraveling mechanisms relevant to
      consciousness as well.

PMID- 15714557
TI  - A new evolutionary scenario for the vertebrate jaw.
AB  - The jaw is one of the earliest innovations in vertebrate history. Several recent
      findings suggest a scenario for jaw evolution as a progression of changes in
      pharyngeal developmental mechanisms. The lamprey, an extant jawless vertebrate,
      constitutes a model for the pre-gnathostome ancestry. Comparing expression
      patterns of regulatory genes between the gnathostome and lamprey embryos may
      enable us to get a glimpse of the essential changes that were responsible for the
      evolution of the jaw. We hypothesize that a specific topographical change of
      inductive tissue interactions to be described here brought about the jaw as an
      evolutionary novelty.

PMID- 15714558
TI  - Of light and length: regulation of hypocotyl growth in Arabidopsis.
AB  - At all stages, plant development results from a complex integration of multiple
      endogenous and environmental signals. The sedentary nature of plants strongly
      enhances the impact of the environment on plant development as compared to animal
      development. The embryonic and postembryonic seedling stem, called the hypocotyl,
      of the model species Arabidopsis (thale cress) has proved to be an excellent
      system for studying such signal interplay in the regulation of growth and
      developmental responses. The extension of the hypocotyl, which is regulated by a
      network of interacting factors, including light and plant hormones, is such a
      process. These regulatory factors often reciprocally regulate their biosynthesis
      and/or signalling. Here we present the current state of knowledge about the
      regulation of hypocotyl growth by a large repertoire of internal and external
      cues.

PMID- 15714559
TI  - A twelve-step program for evolving multicellularity and a division of labor.
AB  - The volvocine algae provide an unrivalled opportunity to explore details of an
      evolutionary pathway leading from a unicellular ancestor to multicellular
      organisms with a division of labor between different cell types. Members of this
      monophyletic group of green flagellates range in complexity from unicellular
      Chlamydomonas through a series of extant organisms of intermediate size and
      complexity to Volvox, a genus of spherical organisms that have thousands of cells
      and a germ-soma division of labor. It is estimated that these organisms all
      shared a common ancestor about 50 +/- 20 MYA. Here we outline twelve important
      ways in which the developmental repertoire of an ancestral unicell similar to
      modern C. reinhardtii was modified to produce first a small colonial organism
      like Gonium that was capable of swimming directionally, then a sequence of larger
      organisms (such as Pandorina, Eudorina and Pleodorina) in which there was an
      increasing tendency to differentiate two cell types, and eventually Volvox
      carteri with its complete germ-soma division of labor.

PMID- 15714560
TI  - Molecular principles of hair follicle induction and morphogenesis.
AB  - Hair follicle (HF) development is the result of neuroectodermal-mesodermal
      interactions, and can be divided into morphologically distinguishable stages
      (induction, organogenesis and cytodifferentiation). The spacing, polarity and
      differentiation patterns of HFs are driven by interacting, self-assembling
      gradients of inhibitors and activators, which are established jointly by the skin
      epithelium and mesenchyme. For HF development to occur, the dominant-negative
      influence of inhibitors of the HF differentiation pathway must be locally
      counteracted by specific antagonists and/or overriden by stimulators of hair
      placode formation. Once a mesenchymal condensate of inductive fibroblasts has
      formed, it takes over control of most subsequent steps of HF organogenesis and of
      epithelial stem cell differentiation into distinct lineages. In this review we
      introduce the morphological characteristics, major underlying principles and
      molecular key players that control HF development. The focus is on recent
      insights into the molecular interactions leading to hair follicle induction, and
      we close with synthesizing a corresponding working hypothesis.

PMID- 15714561
TI  - The choroid plexus in the rise, fall and repair of the brain.
AB  - The choroid plexuses (CPs) are involved in the most-basic aspects of neural
      function including maintaining the extracellular milieu of the brain by actively
      modulating chemical exchange between the CSF and brain parenchyma, surveying the
      chemical and immunological status of the brain, detoxifying the brain, secreting
      a nutritive "cocktail" of polypeptides and participating in repair processes
      following trauma. This diversity of functions may mean that even modest changes
      in the CP can have far-reaching effects. Indeed, changes in the anatomy and
      physiology of the CP have been linked to aging and several CNS diseases. It is
      also possible that replacing diseased or transplanting healthy CP might be useful
      for treating acute and chronic brain diseases. This review focuses on the wide
      ranging and under-appreciated functions of the CP, alterations of these functions
      in aging and neurodegeneration, and recent demonstrations of the therapeutic
      potential of transplanted CP for neural trauma.

PMID- 15714562
TI  - NO flowering.
AB  - The complex control of flowering time ensures that plants flower in conditions
      favourable for reproductive success. A recent study adds another dimension to
      this established complexity by revealing that nitric oxide (NO) represses
      flowering in Arabidopsis. The analysis of recently identified mutants that either
      overproduce or are compromised in endogenous NO production has identified NO
      sensitive features of the circuitry of flowering time control: NO acts to repress
      the amplification of gene expression dependent on the circadian clock and
      promotes the accumulation of mRNA encoding a key repressor of flowering, FLC.

PMID- 15714563
TI  - PAD: the smoking gun behind arginine methylation signaling?
AB  - Post-translational modifications (PTM) supply the proteome with functional and
      regulatory diversity. Modifications including phosphorylation, acetylation and
      methylation have been identified in eucaryotic proteins. For all but the last,
      corresponding "de-modifying" enzymes exist to remove the PTM tag returning the
      protein to its basal state. Recently, a novel mechanism in which peptidylarginine
      deiminase (PAD4) converts histone H3 and H4 methyl arginine residues into
      citrulline was proposed to regulate estrogen-responsive gene transcription.1,2
      These data, the first to provide a mechanistic basis for the dynamic changes
      observed in a subset of protein arginine methylated substrates,3 lead to a host
      of questions concerning the generality of this mechanism for non-histone targets
      of the protein arginine methyltransferases (PRMTs).

PMID- 15714564
TI  - Chiral ion-exchange capillary electrochromatography of arylglycine amides with
      dextran sulfate as a pseudostationary phase.
AB  - A low-cost tunable chiral ion-exchange capillary electrochromatographic method
      has been developed for the separation of arylglycine amide racemic mixtures with
      dextran sulfate (DS) as an anionic and chiral pseudostationary phase and Tris
      tartrate as a buffer system. The concentrations of DS and Tris had opposite
      influences on retention and resolution and could serve as ideal factors to finely
      tune the running speed and chiral resolution. Tartrate and pH largely impact the
      separation but pH should be confined within 3.0-5.5, only suitable for coarse
      tuning, while tartrate was preserved as the key buffering reagent, normally
      maintained at 40 mmol/L. With a working system composed of 0.1-1.0% DS, 20-60
      mmol/L Tris, and 40 mmol/L tartrate at pH 3.50-4.50, the enantioresolution of
      arylglycine amides was shown to be dependent on their chemical structure: The
      chiral resolution increased when the hydrogen at the alpha-amino group or at the
      p-position of phenyl ring was replaced by other larger group(s) but the
      resolution decreased when the group at the o- or m-site on the phenyl ring was
      enlarged. Further, the electronegative substitute of -Cl had larger resolution
      increment than methyl or methoxy at the position p- of phenyl ring but much lower
      increment at position m-. It is possible to well explain the resolution variation
      phenomenon by considering the group resistance and the variation of hydrogen
      bonds formed inside the amino amides and between the solutes and DS. The amido
      group was shown irreplaceable to have chiral resolution with DS alone as an ionic
      and chiral pseudostationary phase.

PMID- 15714565
TI  - Conformational effects on the performance and selectivity of a polymeric
      pseudostationary phase in electrokinetic chromatography.
AB  - The effect of the conformation of a polymeric pseudostationary phase on
      performance and selectivity in electrokinetic chromatography was studied using an
      amphiphilic pH-responsive polymer that forms compact intramolecular aggregates
      (unimer micelles) at low pH and a more open conformation at high pH. The change
      in conformation was found to affect the electrophoretic mobility, retention,
      selectivity, and separation efficiency. The low-pH conformer has higher
      electrophoretic mobility and greater affinity for most solutes. The unimer
      micelle conformation was also found to provide a solvation environment more like
      that of micelles and other amphiphilic self-associative polymers studied
      previously. It was not possible to fully characterize the effect of conformation
      on efficiency, but very hydrophobic solutes with long alkyl chains appeared to
      migrate with better efficiency when the unimer micelle conformation was employed.
      The results imply that polymers with a carefully optimized lipophilic-hydrophilic
      balance that allow self-association will perform better as pseudostationary
      phases. In addition, the results show that electrokinetic chromatography is a
      useful method for determining the changes in solvation environment provided by
      stimuli-responsive polymers with changes in the conditions.

PMID- 15714566
TI  - Capillary electrochromatography of caffeine and its metabolites in rat brain
      microdialysate.
AB  - A capillary electrochromatography (CEC) method has been developed for the
      separation of caffeine and its two metabolites 1-methylxanthine (1-MX) and 1,7
      dimethylxanthine (1,7-DX). The stationary phase was 3-(1,8-naphthalimido) propyl
      modified silyl silica gel (NAIP) and the best separations were achieved with 4.0
      mM citrate buffer (pH 5.0) containing 80% methanol at an applied voltage of 25
      kV. The compounds were completely separated in less than 3.5 min with good
      repeatability, which was approximately 3-times less than that in high-performance
      liquid chromatography (HPLC) with NAIP. The proposed method coupled with
      microdialysis was successfully applied to the monitoring of caffeine
      concentration in rat brain with detection limits of 1.11 microg/mL.

PMID- 15714567
TI  - Separation strategy for acidic chiral pharmaceuticals with capillary
      electrochromatography on polysaccharide stationary phases.
AB  - The effect of five factors on the capillary electrochromatographic
      enantioseparation of acidic compounds was studied using an experimental design.
      The studied factors were pH, acetonitrile content in the mobile phase,
      temperature, buffer concentration, and applied voltage. These experiments allowed
      defining a generic separation strategy applicable on acidic compounds with
      chemical and structural diversity. The starting screening conditions consist of a
      45 mM ammonium formate electrolyte at pH 2.9 mixed with 65% acetonitrile, an
      applied voltage of 15 kV, and a temperature of 25 degrees C. The screening phase
      occasionally can be followed by an optimization procedure. Evaluation of the
      proposed strategy pointed out that it allows achieving baseline resolution within
      a relatively short time when a beginning of separation is obtained at the
      starting conditions. This strategy revealed enantioselectivity for 11 compounds
      out of 15, of which 10 could be baseline-separated after the proposed
      optimization steps.

PMID- 15714568
TI  - Electrochromatographic evaluation of a silica monolith capillary column for
      separation of basic pharmaceuticals.
AB  - A silica-based monolithic capillary column was prepared via a sol-gel process.
      The continuous skeleton and large through-pore structure were characterized by
      scanning electron microscopy (SEM). The native silica monolith has been
      successfully employed in the electrochromatographic separation of beta-blockers
      and alkaloids extracted from traditional Chinese medicines (TCMs). Column
      efficiencies greater than 250 000 plates/m for capillary electrochromatography
      (CEC) separation of basic compounds were obtained. It was observed that retention
      of basic pharmaceuticals on the silica monolith was mainly contributed by a
      cation-exchange mechanism. Other retention mechanisms including reversed-phase
      and normal-phase mechanisms and electrophoresis of basic compounds also played a
      role in separation. A comparison of the differences between CEC and capillary
      zone electrophoresis (CZE) separation was also discussed.

PMID- 15714569
TI  - Chiral recognition ability of an (S)-naproxen- imprinted monolith by capillary
      electrochromatography.
AB  - The racemic naproxen was selectively recognized by capillary
      electrochromatography (CEC) on an (S)-naproxen-imprinted monolith, which was
      prepared by an in situ thermal-initiated polymerization. The recognition
      selectivity of a selected monolith strictly relied on the CEC conditions
      involved. The factors that influence the imprinting selectivity as well as the
      electroosmotic flow (EOF), including the applied voltage, organic solvent, salt
      concentration and pH value of the buffer, column temperature, and surfactant
      modifiers were systematically studied. Once the column was prepared, the
      experiment results showed that the successful chiral recognition was dependent on
      CEC variables. For example: the recognition could be observed in acetonitrile and
      ethanol electrolytes, while methanol and dimethyl sulfoxide (DMSO) electrolytes
      had no chiral recognition ability. The buffer with pH values of 2.6 or 3.0 at a
      higher salt concentration had chiral recognition ability. Column temperatures of
      25-35 degrees C were optimal. Three surfactants, sodium dodecyl sulfate (SDS),
      cetyltrimethylammonium bromide (CTAB), and polyoxyethylene sorbitan monolaurate
      (Tween 20), can improve the recognition. Baseline resolution was obtained under
      optimized conditions and the column efficiency of the later eluent (S)-naproxen
      was 90 000 plates/m.

PMID- 15714571
TI  - Investigation of the stability of polyelectrolyte multilayer coatings in open
      tubular capillary electrochromatography using laser scanning confocal microscopy.
AB  - A simple polyelectrolyte multilayer (PEM) coating procedure was used for the
      development of stable modified capillaries. PEM coatings were constructed in
      fused-silica capillaries using alternating rinses of cationic and anionic
      polyelectrolytes. The multilayer coatings investigated in this study consisted of
      two and twenty layer pairs, or bilayers. A bilayer is one layer of a cationic
      polymer and one layer of an anionic polymer. Poly(diallyldimethylammonium
      chloride) was used as the cationic polymer, and the polymeric surfactant
      poly(sodium N-undecanoyl-L-leucylvalinate) was used as the anionic polymer.
      Previous studies for both chiral and achiral separations have shown that PEM
      coated capillaries have excellent reproducibilities, remarkable endurance, and
      strong stabilities against extreme pH values when used in open-tubular capillary
      electrochromatography (OT-CEC). In this study, the stability of the coatings was
      further investigated after exposure to 0.1 M and 1.0 M NaOH. Structural changes
      of these coatings were monitored using laser scanning confocal microscopy (LSCM)
      after flushing the capillaries with NaOH. This technique allowed observation of
      the degradation of the coatings. Observations are discussed in terms of
      separations using OT-CEC. Electropherograms obtained from the chiral separation
      of 1,1'-binaphthyl-2,2'-dihydrogenphosphate in OT-CEC showed a decrease in
      selectivity and an increase in electroosmotic mobility after long exposure to
      NaOH. The ability to recover the capillaries by exposure to NaOH was also
      demonstrated. Measurements of electroosmotic mobility and selectivity showed that
      2-bilayer and 20-bilayer PEM coatings could be completely removed from the
      capillary surface after approximately 3.5 and 9.5 h, respectively, of continuous
      exposure to 1 M NaOH.

PMID- 15714570
TI  - Analysis of antiepileptic drugs in biological fluids by means of electrokinetic
      chromatography.
AB  - An overview of the electrokinetic chromatographic methods for the analysis of
      antiepileptic drug levels in biological samples is presented. In particular,
      micellar electrokinetic capillary chromatography is a very suitable method for
      the determination of these drugs, because it allows a rapid, selective, and
      accurate analysis. In addition to the electrokinetic chromatographic studies on
      the determination of antiepileptic drugs, some information regarding sample
      pretreatment will also be reported: this is a critical step when the analysis of
      biological fluids is concerned. The electrokinetic chromatographic methods for
      the determination of recent antiepileptic drugs (e.g., lamotrigine,
      levetiracetam) and classical anticonvulsants (e.g., carbamazepine, phenytoin,
      ethosuximide, valproic acid) will be discussed in depth, and their
      pharmacological profiles will be briefly described as well.

PMID- 15714572
TI  - Recent advances in micellar electrokinetic chromatography.
AB  - This review contains nearly 200 reference citations, and covers advances in
      electrokinetic capillary chromatography based on micelles, including stabilized
      micelle complexes, polymeric and mixed micelles from 2003-2004. Detection
      strategies, analyte determinations, and applications in micellar electrokinetic
      capillary chromatography (MEKC) are discussed. Information regarding methods of
      analyte concentration, analyte specific analyses, and nonstandard micelles has
      been summarized in tabular form to provide a means of rapid access to information
      pertinent to the reader.

PMID- 15714573
TI  - Lipid vesicles in capillary electrophoretic techniques: characterization of
      structural properties and associated membrane-molecule interactions.
AB  - This paper reviews the use of lipid vesicles as model membranes in capillary
      electrophoresis (CE). The history and utility of CE in the characterization of
      microparticles is summarized, focusing on the application of colloidal
      electromigration theories to lipid vesicles. For instance, CE experiments have
      been used to characterize the size, surface properties, enclosed volumes, and
      electrophoretic mobilities of lipid vesicles and of lipoprotein particles.
      Several techniques involving small molecules or macromolecules separated in the
      presence of lipid vesicles are discussed. Interactions between the analytes and
      the lipid vesicles - acting as a pseudostationary phase or coated stationary
      phase in electrokinetic chromatography (EKC) - can be used to obtain additional
      information on the characteristics of the vesicles and analytes, and to study the
      biophysical properties of membrane-molecule interactions in lipid vesicles and
      lipoproteins. Different methods of determining binding constants by EKC are
      reviewed, along with the relevant binding constant calculations and a discussion
      of the application and limitations of these techniques as they apply to lipid
      vesicle systems.

PMID- 15714576
TI  - Capillary electrophoresis direct enantioseparation of aromatic amino acids based
      on mixed chelate-inclusion complexation of aminoethylamino-beta-cyclodextrin.
AB  - 6(A)-(2-Aminoethylamino)-6(A)-deoxy-beta-cyclodextrin (CDen) was synthesized and
      formed a binary complex with Cu(II) which was shown to be an effective chiral
      selector for separation of underivatized amino acid enantiomers in capillary
      electrophoresis (CE). Moreover, the chiral resolution was greatly enhanced by the
      presence of polyethyl glycol (PEG) and tert-butyl alcohol in the running buffer.
      The optimum experimental conditions were 20 mmol/L CDen, 20 mmol/L
      CuSO(4).5H(2)O, 5.0 mg/mL PEG20000 and 1.0% v/v tert-butyl alcohol, pH 5.80. With
      the proposed method, the four selected aromatic chiral amino acid pairs were
      separated in less than 15 min.

PMID- 15714578
TI  - Enantioseparation of chiral allenic acids by micellar electrokinetic
      chromatography with cyclodextrins as chiral selector.
AB  - Enantioseparation of chiral aryl allenic acids by micellar electrokinetic
      chromatography (MEKC) with cyclodextrins (CDs) as chiral selectors was described.
      The screen of chiral selectors (beta-CD, gamma-CD, and hydroxypropyl (HP)-gamma
      CD) showed that the enantioseparation was not only dependent on the type of CD
      but also the presence of 2-propanol in the buffer. In order to optimize the
      operational parameters, the effect of the concentration of CDs, sodium dodecyl
      sulfate (SDS), and 2-propanol, as well as the buffer ionic strength and pH on
      enantioseparation were studied. It was proved that the concentration of CDs, 2
      propanol, and the buffer ionic strength were the critical parameters. Under
      optimal conditions, baseline separations of all seven allenic acid enantiomers
      were achieved. Furthermore, the method validation in terms of repeatability,
      linearity, limit of detection (LOD), and limit of quantitation (LOQ) were
      performed. Using the present method, the optical purity of a nonracemic sample
      with the enantiomeric excess (e.e.%) value of 99.65% was determined.

PMID- 15714579
TI  - Chiral separation based on ligand-exchange capillary electrophoresis using a
      copper(II)-L-ornithine ternary complex as selector.
AB  - A ligand-exchange capillary electrophoresis was explored, with L-ornithine as the
      ligand and copper(II) as the central ion. Its applicability was demonstrated with
      underivatized and dansyl amino acids, a dipeptide, and drugs with amino alcohol
      structure. The enantioselectivity was found to be strongly dependent on pH and
      copper(II)-L-Orn complex concentration. Due to the adsorption of the positively
      charged species onto the capillary inner walls, the chiral separation selectivity
      is very high while the efficiency is relatively low. Permanent 1,3-propanediamine
      coated capillaries show an improved separation efficiency and theoretical plate
      numbers increasing from 10(4) to 10(5). Similar phenomena were observed when
      sodium dodecyl sulfate (SDS) micelles were added to the copper(II) complex
      solution. The poor separation efficiency of chiral compounds in uncoated
      capillaries may result from the low rate of the ligand-exchange reactions, and
      the high enantioselectivity may derive from the complexing process in the
      adsorbed phase.

PMID- 15714580
TI  - MyD88 and TLR2, but not TLR4, are required for host defense against Cryptococcus
      neoformans.
AB  - We investigated here the potential role of Toll-like receptors (TLR) and the
      adaptor protein MyD88 in innate immunity responses to Cryptococcus neoformans, a
      pathogenic encapsulated yeast. Peritoneal macrophages from MyD88(-/-) or TLR2(-/
      ) mice released significantly less TNF-alpha, compared with wild-type controls,
      after in vitro stimulation with whole yeasts. In contrast, no differences in TNF
      alpha release were noted between macrophages from C3H/HeJ mice, which have a loss
      of function mutation in TLR4, relative to C3H/HeN controls. When MyD88- or TLR2
      deficient mice were infected with low doses of the H99 serotype A strain, all of
      the control animals, but none of MyD88(-/-) and only 38% of the TLR2(-/-) animals
      survived, in association with higher fungal burden in the mutant mice. Both
      MyD88(-/-) and TLR2(-/-) animals showed decreased TNF-alpha, IL-12p40 and/or IFN
      gamma expression in various organs during infection. No difference in
      susceptibility to experimental cryptococcosis was found between C3H/HeJ mice and
      C3H/HeN controls. In conclusion, our data indicate that TLR2 and MyD88, but not
      TLR4, critically contribute to anti-cryptococcal defenses through the induction
      of increased TNF-alpha, IL-12 and IFN-gamma expression.

PMID- 15714581
TI  - CCL22-induced responses are powerfully enhanced by synergy inducing chemokines
      via CCR4: evidence for the involvement of first beta-strand of chemokine.
AB  - In an attempt to clarify how cells integrate the signals provided by multiple
      chemokines expressed during inflammation, we have uncovered a novel mechanism
      regulating leukocyte trafficking. Our data indicate that the concomitant exposure
      to CCR4 agonists and CXCL10/IP-10 strongly enhances the chemotactic response of
      human T lymphocytes. This enhancement is synergistic rather than additive and
      occurs via CCR4 since it persists after CXCR3 blockade. Besides chemotaxis, other
      cellular responses are enhanced upon stimulation of CCR4-transfected cells with
      CCL22/MDC plus CXCL10. Several other chemokines in addition to CXCL10 were able
      to increase CCL22-mediated chemotaxis. The first beta-strand of the chemokine
      structure is highly and specifically implicated in this phenomenon, as
      established using synergy-inducing and non-synergy-inducing chimeric chemokines.
      As shown in situ for skin from atopic and allergic contact dermatitis patients,
      this organ becomes the ideal environment in which skin-homing CCR4(+) T
      lymphocytes can accumulate under the stimulus offered by CCR4 agonists, together
      with the synergistic chemokines that are concomitantly expressed. Overall, our
      results indicate that chemokine-induced synergism strengthens leukocyte
      recruitment towards tissues co-expressing several chemokines.

PMID- 15714582
TI  - Graft rejection mediated by CD4+ T cells via indirect recognition of alloantigen
      is associated with a dominant Th2 response.
AB  - CD4(+) T cells that respond to indirectly presented alloantigen have been shown
      to mediate chronic rejection, however, the role of the indirect pathway in acute
      rejection has yet to be completely elucidated. To this end, BALB/c or C57BL/6
      mice were depleted of CD8(+) T cells and transplanted with class II
      transactivator (CIITA)-deficient cardiac allografts, which cannot directly
      present class II alloantigens to CD4(+) T cells. In this manner, the rejection
      response by CD4(+) cells was forced to rely upon the indirect recognition
      pathway. When not depleted of CD8(+) cells, both BALB/c and C57BL/6 mice rejected
      CIITA-/- allografts and a polarized Th1 response was observed. In contrast, when
      BALB/c recipients of CIITA-/- allografts were depleted of CD8(+) T cells, the
      grafts were acutely rejected and a strong Th2 response characterized by
      eosinophil influx into the graft was observed. Interestingly, CD8-depleted
      C57BL/6 recipients of CIITA-/- allografts did not acutely reject their
      transplants and a Th2 response was not mounted. These findings indicate that
      CD4(+) T cells responding to indirectly presented alloantigens mediate graft
      rejection in a Th2-dominant manner, and provide further evidence for the role of
      Th2 responses in acute graft rejection.

PMID- 15714584
TI  - Contribution of stromal cells to the migration, function and retention of plasma
      cells in human spleen: potential roles of CXCL12, IL-6 and CD54.
AB  - Plasma cells (PC) localize to discrete areas of secondary lymphoid tissue and
      bone marrow (BM). The positioning of PC in different sites is believed to be
      regulated by chemokines and adhesion molecules expressed by accessory cells in
      the lymphoid tissue microenvironment. However, the mechanisms responsible for the
      positioning of PC within the red pulp (RP) of human spleen have not been
      elucidated. Therefore, we examined the contribution of human splenic stromal
      cells to the migration and function of human PC. Splenic PC expressed the
      chemokine receptor CXCR4 and responded to its ligand CXCL12. In contrast, PC
      lacked CXCR5 and CCR7, and consequently exhibited minimal migration towards
      CXCL13 and CCL21. Splenic stromal cells proved to be a rich source of CXCL12, and
      could induce the migration of human B cells. Furthermore, they supported Ig
      production by splenic PC mainly by secreting IL-6. Lastly, a striking difference
      between splenic and BM PC was the constitutive expression of CD11a by only
      splenic PC. Notably, splenic stromal cells expressed high levels of CD54, the
      counter-structure of CD11a, and splenic PC were positioned adjacent to stromal
      cells in the RP. Thus, we propose that stromal cells attract PC to the RP and
      contribute to their retention and function through the combined expression of
      CXCL12, CD54 and IL-6.

PMID- 15714583
TI  - The role of TCR stimulation and TGF-beta in controlling the expression of
      CD94/NKG2A receptors on CD8 T cells.
AB  - Following antigen recognition, murine CD8 T cells express CD94/NKG2A receptors.
      Our results show that this up-regulation occurs rapidly in vitro and is
      accompanied by an approximately 8-fold increase in CD94 and approximately 125
      fold increase in NKG2A mRNA. In contrast, only a twofold increase in NKG2C mRNA
      is noted. The addition of TGF-beta, but not IL-10, IL-12 or IL-15, leads to a
      further increase in cell membrane expression of these receptors, as well as a
      approximately 6-fold increase in mRNA for both chains. TGF-beta also increases
      CD94/NKG2A expression on memory CD8 T cells that are re-exposed to antigen. The
      effect of TGF-beta on increasing CD94/NKG2A expression on both naive and memory
      CD8 T cells occurs only when there is a concurrent stimulation through the TCR.
      In contrast, TGF-beta does not increase expression of CD94/NKG2A on resting or
      activated NK cells. We also show by using purified CD8 T cells, that TGF-beta
      acts directly on these cells. These results implicate a role for both antigen and
      TGF-beta in increasing expression of inhibitory CD94/NKG2A receptors on CD8 T
      cells.

PMID- 15714585
TI  - Peptide immunization excludes antigen-specific T cells from splenic lymphoid
      compartments.
AB  - Using adoptive transfer of TCR-transgenic T cells, we examined the homing of
      transgenic T cells to splenic compartments in situ. After systemic immunization
      with peptide or protein antigen, the location of clonotypic T cells, cytokine
      production, cell surface markers, and apoptosis were assessed. There were
      distinct differences in the splenic homing of CD4(+) TCR-transgenic T cells in
      mice immunized with peptide as compared to mice immunized with whole-protein
      antigen. T cells in peptide-immunized mice were found almost exclusively in the
      splenic red pulp, but not in the T and B cell zones (white pulp), while the
      majority of T cells immunized with whole protein were found in the white pulp.
      Many more Fas ligand-expressing and apoptotic cells were present after peptide
      immunization than after whole-protein immunization. Localization of IL-4-, IL-2-
      and IFN-gamma-producing cells to the lymphocyte-containing splenic white pulp was
      only observed with whole-protein immunization. The unique homing and increased
      apoptosis of immune cells post peptide immunization may help explain the
      ineffectiveness of many peptide vaccines. Linkage of the same peptide epitope to
      a carrier protein increased white pulp T cell localization and decreased
      apoptosis, suggesting a strategy to enhance peptide vaccine responses.

PMID- 15714588
TI  - Much anticipated--the bioactive conformation of epothilone and its binding to
      tubulin.

PMID- 15714590
TI  - Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1.
AB  - Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by
      the innate immune system. For LP, it has been shown that TLR2 is the essential
      receptor in cellular activation. However, molecular mechanisms of LP recognition
      are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopeptide
      N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-(R)-cysteinyl-seryl
      (lysyl)(3)-lysine (Pam(3)CSK(4)) to study the roles of CD14, TLR2 and TLR1 in
      binding and signaling of LP and their molecular interactions in human cells. The
      activity of Pam(3)CSK(4)-FLAG was TLR2 dependent, whereas the binding was enabled
      by CD14, as evaluated by flow cytometry and confocal microscopy. Using FRET and
      FRAP imaging techniques to study molecular associations, we could show that after
      Pam(3)CSK(4)-FLAG binding, CD14 and Pam(3)CSK(4)-FLAG associate with TLR2 and
      TLR1, and TLR2 is targeted to a low-mobility complex. Thus, LP binding to CD14 is
      the first step in the LP recognition, inducing physical proximity of CD14 and LP
      with TLR2/TLR1 and formation of the TLR2 signaling complex.

PMID- 15714591
TI  - Killer cell immunoglobulin-like receptors (KIR) of the African-origin sabaeus
      monkey: evidence for recombination events in the evolution of KIR.
AB  - Killer cell immunoglobulin (Ig)-like receptors (KIR) were characterized in the
      West African sabaeus monkey (Chlorocebus sabaeus) to elucidate the mechanism by
      which diversity evolves in this family of molecules. Complementary DNA encoding
      four forms of KIR molecules, including KIR3DL, KIR2DL4, KIR2DL5, and KIR3DH
      forms, were identified in two unrelated sabaeus monkeys. A novel hybrid form
      showing features found in both KIR2DL5 and KIR3DH was also identified. Both the
      KIR3DL and KIR3DH forms from the sabaeus monkey were considerably more
      polymorphic than any KIR form identified in great apes or humans. The polymorphic
      residues of the three Ig-like domains were frequently located in structural
      loops, indicating that point mutations have occurred in these regions. The three
      Ig-like domains of the KIR3D forms of six primate species were found to have
      different patterns of clustering in phylogenetic trees, suggesting that each Ig
      like domain has a distinct phylogenetic history. This variation in relationships
      suggests that repeated recombination events have occurred between the Ig-like
      domains during the evolution of the KIR family in primates. Recombination between
      individual Ig-like domains, in addition to point mutations, provides a mechanism
      for generating the diversity of the KIR genes.

PMID- 15714592
TI  - Elevated nuclear maspin expression is associated with microsatellite instability
      and high tumour grade in colorectal cancer.
AB  - Maspin, a member of the serpin family, has been reported to suppress metastasis
      and angiogenesis in breast and prostate cancers. Overexpression of maspin was
      associated with adverse prognostic features in several other tumours. In this
      study, expression of maspin was analysed in 41 colorectal carcinomas with high
      frequency microsatellite instability (MSI-H) and 159 microsatellite stable
      colorectal cancers (MSS/MSI-L) by immunohistochemistry (IHC) and partly by
      relative quantitative real-time RT-PCR and western blot analyses. Significant
      upregulation of maspin expression was found in MSI-H tumours compared to both
      MSS/MSI-L tumours and matched benign colonic mucosa. Increased maspin expression
      was also found in three MSI-H colon cancer cell lines, but not in three MSS colon
      cancer cell lines by RT-PCR and western blot analyses. Regulation of maspin
      expression depended on promoter methylation as tissue specimens and cell lines
      expressing maspin showed unmethylated maspin promoters, whereas promoter
      hypermethylation was found in specimens with loss of maspin expression. Intense
      nuclear maspin immunostaining was seen specifically in MSI-H tumours (p = 0.013),
      de-differentiated tumours (p = 0.006), and at the invasion front. These findings
      provide new insights into the role of maspin in colorectal cancer progression and
      may be useful for diagnosis and treatment strategies.

PMID- 15714593
TI  - Frequency of BRAF T1796A mutation in papillary thyroid carcinoma relates to age
      of patient at diagnosis and not to radiation exposure.
AB  - In this study, the frequency of BRAF mutation was investigated in a series of 67
      cases of papillary thyroid cancer (PTC) in patients from Ukraine. Thirty-two
      patients were aged 30 years or older at the time of diagnosis and 35 were under
      16. Tumour was microdissected from paraffin wax-embedded sections, DNA extracted,
      and the presence of the BRAF T1796A mutation demonstrated by two different
      methods: PCR followed by restriction enzyme digestion or primer extension assay
      and detection using MALDI-TOF mass spectrometry. Eighteen (58%) of the adult
      cases, but only one of the 35 cases aged less than 16 harboured a BRAF T1796A
      mutation. There was complete agreement between the two methods used, suggesting
      that the MALDI-TOF assay is a robust alternative to conventional mutation
      analysis. RET rearrangement was also examined in the young cohort. The overall
      frequency of RET rearrangement was 45.7%. Eight of the younger group of patients
      were born after 1 December 1986 and were therefore not exposed to radioiodine in
      fallout from Chernobyl. None of the PTCs from these eight patients were positive
      for BRAF mutation. The frequency of RET rearrangement was 44% in the 27 cases
      exposed to radiation and 50% in the eight not exposed. These results suggest that
      the different molecular biological profiles observed are associated with the age
      of the patient at diagnosis with PTC, rather than being associated with radiation
      exposure.

PMID- 15714594
TI  - Investigations of taxoids by electrospray and atmospheric pressure chemical
      ionization with tandem mass spectrometry.
AB  - The fragmentation behavior of taxoids was studied using electrospray (ESI) and
      atmospheric pressure chemical ionization (APCI) sources with multi-stage tandem
      mass spectrometry. In the positive ion mode taxoids gave prominent [M+Na]+ and
      [M+K]+ ions with the ESI source, and [M+NH4]+ or [M+H]+ ions with the APCI
      source. The MS/MS fragmentations of ions produced by APCI and ESI sources were
      very similar. For both sources, the presence of cinnamoyl or benzoyl groups could
      be characterized by initial losses of 148 or 122 u, respectively, from molecular
      adduct ions. However, the elimination of cinnamic acid was relatively difficult
      for the molecular adduct ions formed by APCI, and was comparable in importance to
      the loss of acetic acid. The other fragments involved losses of CH2CO, CO, and
      H2O. The 5/7/6 type taxoids underwent characteristic losses of 58 or 118 u from
      ions produced by both APCI and ESI sources. The fragmentation behavior was
      remarkably influenced by substitution locations. The elimination of the C-10
      benzoyl group was usually the first fragmentation step, while that of the C-2
      benzoyl group was relatively difficult. The acetoxyl group at C-7 was more active
      than those at C-2, C-9, and C-10, which in turn were more active than that at C
      4. These fragmentation rules could facilitate the rapid screening and structural
      characterization of taxoids in plant extracts by high-performance liquid
      chromatography/mass spectrometry (HPLC/MS).

PMID- 15714595
TI  - Characterization of dendritic cells in differentiated thyroid cancer.
AB  - In this study, the types and localization pattern of dendritic cells (DCs), the
      expression of chemokines on carcinoma cells and of the relevant receptors on DCs,
      and the adhesion molecules expressed on vascular endothelial cells and DCs were
      examined in thyroid carcinomas. Papillary carcinoma had a higher frequency of
      CD1a(+) immature DCs than other thyroid tumours. Macrophage inflammatory protein
      (MIP)-3 alpha was expressed strongly on the majority of papillary carcinoma cells
      and weakly on a minority of follicular carcinoma cells. DCs positive for
      chemokine receptor-6 (CCR-6) were densely accumulated in papillary carcinoma. DC
      SIGN(+) DCs were accumulated in papillary carcinoma but rarely in follicular
      carcinoma. A binding assay for DC-SIGN-mediated adhesion of isolated DCs revealed
      significant inhibition of DC adhesion to papillary carcinoma tissues by
      neutralizing antibodies against intercellular adhesion molecule-2 or DC-SIGN.
      These results clearly indicated marked differences between papillary carcinoma
      and follicular carcinoma in the accumulation of immature DCs, in MIP-3 alpha
      expression on carcinoma cells, and in the frequency of CCR-6(+) DCs and DC
      SIGN(+) DCs.

PMID- 15714596
TI  - On the stability of the organic dication of the bisquaternary ammonium salt
      decamethoxinum under liquid secondary ion mass spectrometry.
AB  - In the course of a liquid secondary ion mass spectrometric (SIMS) investigation
      on a bisquaternary ammonium antimicrobial agent, decamethoxinum, unusual pathways
      of fragmentation of the organic dication M2+ of this bisquaternary salt, with
      preservation of the doubly charged state of the fragments, were observed. To
      reveal the structural and electronic parameters of decamethoxinum, which are
      responsible for the stabilization of its organic dication in the gas phase, a
      comprehensive SIMS study using metastable decay, collision-induced dissociation
      and kinetic energy release techniques complemented by ab initio quantum chemical
      calculations was performed. Pathways of fragmentation of two main precursors
      originating from decamethoxinum-organic dication M2+ and its cluster with a Cl-
      counterion [M.Cl]+-and a number of their primary fragments were established and
      systematized. Differences in the pathways of fragmentation of M2+ and [M.Cl]+
      were revealed: the main directions of [M.Cl]+ decay involve dequaternization
      similar to thermal degradation of this compound, while in M2+ fragmentation via
      loss of one and two terminal radicals with preservation of the doubly charged
      state of the fragments dominates over charge separation processes. It was shown
      that pairing of the dication with a Cl- anion does not preserve the complex from
      fragmentation via separation of two positively charged centers or neutralization
      (dequaternization) of one such center. At the same time the low abundance of M2+
      in the SIMS spectra is to a larger extent controlled by a probability of M2+
      association with an anion than by the decay of the dication per se. Quantum
      chemical calculations of the structural and electronic parameters of the
      decamethoxinum dication have revealed at least three features which can provide
      stabilization of the doubly charged state. Firstly, in the most energetically
      favorable stretch conformation the distance between the quaternary nitrogens (rN1
      N2=1.39 nm) is relatively large. Secondly, an intramolecular solvation of
      quaternary groups by carbonyl oxygens of the adjacent groups of the dication
      occurs, which contribute to structural stabilization. Thirdly, an important
      feature of the electronic structure of the dication is the presence of a partial
      negative charge on the nitrogen atoms and smearing of a positive charge mainly
      over the hydrogens of alkyl groups attached to the quaternary nitrogens, which
      reduces the net repulsion between the quaternary groups. The possible influence
      of charge smearing on the kinetic energy released on the dication fragmentation
      is discussed.

PMID- 15714597
TI  - Resolution, quantification and confirmation of betamethasone and dexamethasone in
      equine plasma by liquid chromatography/tandem mass spectrometry.
AB  - This method describes the simultaneous separation, identification, quantification
      and confirmation of betamethasone (BTM) and dexamethasone (DXM) in equine plasma
      by liquid chromatography (LC) integrated with multidimensional tandem mass
      spectrometry. Analytes were directly extracted from equine plasma by methyl tert
      butyl ether (MTBE). The residues were reconstituted with sample solvent. LC
      separation of the analytes was performed on a Hypercarb column using
      acetonitrile/water/formic acid (95:5:0.5, v/v/v) as the mobile phase. Sample
      screening, quantification and confirmation were performed in multiple reaction
      monitoring (MRM) mode. The method was linear over the concentration range of 0.1
      75 ng/mL for both analytes. Limit of detection (LOD) was 50 pg/mL and that of
      quantification (LOQ) was 100 pg/mL for both analytes. The limit of confirmation
      (LOC) for the presence of BTM or DXM by MRM was 0.5 ng/mL. The intra-and inter
      day precisions expressed as coefficient of variation (CV) for quantification of
      DXM and BTM from 0.1 to 50 ng/mL were less than 7% and the accuracy was in the
      range of 97-105%. This method is capable of distinguishing BTM from DXM when both
      analytes are simultaneously present in equine plasma. Measurement uncertainty for
      both analytes was estimated at less than 16%. The method is rapid, specific,
      selective, sensitive, simple and reliable. The importance of this method is its
      usefulness in directly identifying and differentiating BTM from DXM without
      derivatization.

PMID- 15714598
TI  - A tandem mass spectrometric study of saccharides at high mass resolution.
AB  - Nine monosaccharides and four disaccharides were mass analyzed using a quadrupole
      time-of-flight tandem mass spectrometer combined with an electrospray ionization
      source. Product ion mass spectra of deprotonated, protonated, and sodiated
      saccharides were observed and were compared within each group of saccharides.
      Each of the deprotonated pentoses, hexoses and disaccharides yielded a
      significantly different product ion mass spectrum with the exception of alpha
      lactose and beta-lactose. The disaccharides alpha- and beta-lactose differ only
      at the glycosidic linkage. Product ion mass spectra of protonated and sodiated
      alpha- and beta-lactose were indistinguishable also.

PMID- 15714599
TI  - Liquid chromatography/tandem mass spectrometry for pharmacokinetic studies of
      20(R)-ginsenoside Rg3 in dog.
AB  - A sensitive and specific liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) method was developed for the investigation of the pharmacokinetics of
      20(R)-ginsenoside Rg3 in dog. The plasma samples were pretreated by liquid-liquid
      extraction and analyzed using LC/MS/MS with an electrospray ionization interface.
      Dioscin was used as the internal standard. The method had a lower limit of
      quantitation of 0.5 ng/mL for Rg3 in 200 microL of plasma or 2 ng/mL in 100
      microL of plasma, which offered a satisfactory sensitivity for the determination
      of Rg3 in plasma. The intra- and inter-day precisions were measured to be below
      8% and accuracy between -1.5 and 1.4% for all quality control samples. This
      quantitation method was successfully applied to pharmacokinetic studies of Rg3
      after both an oral and an intravenous administration to beagle dogs. No Rh2 and
      protopanaxadiol were detected in plasma.

PMID- 15714600
TI  - Simultaneous determination of paracetamol and dextropropoxyphene in human plasma
      by liquid chromatography/tandem mass spectrometry: application to clinical
      bioequivalence studies.
AB  - A liquid chromatography/mass spectrometry method for simultaneous determination
      of paracetamol and dextropropoxyphene in human plasma is described. Paracetamol
      and dextropropoxyphene, together with their internal standards (tolbutamide and
      pyrroliphene), were extracted from 0.5 mL of plasma using solid-phase extraction.
      The chromatography was performed using a Thermo Hypersil APS-2 Amino column (250
      mm x 4.6 mm, 5 microm) with a mobile phase consisting of acetonitrile and 0.4%
      glacial acetic acid in water (20:80). The total run time was 6 min for each
      sample. The triple-quadrupole mass spectrometer was operated in both positive
      (for detection of dextropropoxyphene and its IS pyrroliphene) and negative (for
      detection of paracetamol and its IS tolbutamide) modes using a polarity-switching
      technique. Multiple reaction monitoring was used for quantification. The method
      was linear over the concentration range of 0.1-20 microg/mL for paracetamol and
      0.5-80 ng/mL for dextropropoxyphene. The intra- and inter-day precision were less
      than 10%, and the accuracy ranged from 92.2-110.9%. The lower limits of
      quantification were 0.1 microg/mL for paracetamol and 0.5 ng/mL for
      dextropropoxyphene. The present method provides a robust, fast and sensitive
      analytical tool for both paracetamol and dextropropoxyphene, and has been
      successfully applied to a clinical bioequivalence study in 14 subjects.

PMID- 15714601
TI  - A high-throughput liquid chromatography/tandem mass spectrometry method for
      screening glutathione conjugates using exact mass neutral loss acquisition.
AB  - Chemically reactive metabolites may cause hepatotoxicity and as a result liver
      failure or other adverse side reactions. Therefore, this is a vital topic of
      interest because early reactive metabolite screening may prevent compound failure
      at a later stage. In order to address this issue, a screening assay has been
      developed to detect the formation of reactive metabolites by using glutathione as
      a trapping reagent, which will allow us to search for phase I metabolites and
      also glutathiones during in vitro metabolite screening using liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) with exact mass. Glutathione
      conjugations when fragmented by the mass spectrometer give a common loss
      corresponding to the pyroglutamic acid moiety, which can be monitored. Until
      recently, this work has been carried out with triple quadrupole technology using
      nominal mass. The advantage of the hybrid quadrupole time-of-flight mass
      spectrometer is the selectivity and sensitivity that can be achieved. Exact
      neutral loss detection is achieved via sequential low- and high-energy MS
      acquisitions. After detection of the loss of the pyroglutamic acid moiety, using
      a window of +/-20 mDa on the high-energy scan, MS/MS is carried out on the parent
      mass of interest to confirm the common neutral loss.

PMID- 15714602
TI  - Text-independent speaker verification using Minimal Resource Allocation Networks.
AB  - This paper presents a text-independent speaker verification system based on an
      online Radial Basis Function (RBF) network referred to as Minimal Resource
      Allocation Network (MRAN). MRAN is a sequential learning RBF, in which hidden
      neurons are added or removed as training progresses. LP-derived cepstral
      coefficients are used as feature vectors during training and verification phases.
      The performance of MRAN is compared with other well-known RBF and Elliptical
      Basis Function (EBF) based speaker verification methods in terms of error rates
      and computational complexity on a series of speaker verification experiments. The
      experiments use data from 258 speakers from the phonetically balancedcontinuous
      speech corpus TIMIT. The results show that MRAN produces comparable error rates
      to other methods with much less computational complexity.

PMID- 15714603
TI  - Unsupervised fuzzy clustering using Weighted Incremental Neural Networks.
AB  - A new more efficient variant of a recently developed algorithm for unsupervised
      fuzzy clustering is introduced. A Weighted Incremental Neural Network (WINN) is
      introduced and used for this purpose. The new approach is called FC-WINN (Fuzzy
      Clustering using WINN). The WINN algorithm produces a net of nodes connected by
      edges, which reflects and preserves the topology of the input data set.
      Additional weights, which are proportional to the local densities in input space,
      are associated with the resulting nodes and edges to store useful information
      about the topological relations in the given input data set. A fuzziness factor,
      proportional to the connectedness of the net, is introduced in the system. A
      watershed-like procedure is used to cluster the resulting net. The number of the
      resulting clusters is determined by this procedure. Only two parameters must be
      chosen by the user for the FC-WINN algorithm to determine the resolution and the
      connectedness of the net. Other parameters that must be specified are those which
      are necessary for the used incremental neural network, which is a modified
      version of the Growing Neural Gas algorithm (GNG). The FC-WINN algorithm is
      computationally efficient when compared to other approaches for clustering large
      high-dimensional data sets.

PMID- 15714604
TI  - On the structure and initial parameter identification of Gaussian RBF networks.
AB  - We consider the efficient initialization of structure and parameters of
      generalized Gaussian radial basis function (RBF) networks using fuzzy decision
      trees generated by fuzzy ID3 like induction algorithms. The initialization scheme
      is based on the proposed functional equivalence property of fuzzy decision trees
      and generalized Gaussian RBF networks. The resulting RBF network is compact, easy
      to induce, comprehensible, and has acceptable classification accuracy with
      stochastic gradient descent learning algorithm.

PMID- 15714605
TI  - An improved transiently chaotic neural network for the maximum independent set
      problem.
AB  - By analyzing the dynamic behaviors of the transiently chaotic neural network and
      greedy heuristic for the maximum independent set (MIS) problem, we present an
      improved transiently chaotic neural network for the MIS problem in this paper.
      Extensive simulations are performed and the results show that this proposed
      transiently chaotic neural network can yield better solutions to p-random graphs
      than other existing algorithms. The efficiency of the new model is also confirmed
      by the results on the complement graphs of some DIMACS clique instances in the
      second DIMACS challenge. Moreover, the improved model uses fewer steps to
      converge to stable state in comparison with the original transiently chaotic
      neural network.

PMID- 15714606
TI  - Step to improve neural cryptography against flipping attacks.
AB  - Synchronization of neural networks by mutual learning has been demonstrated to be
      possible for constructing key exchange protocol over public channel. However, the
      neural cryptography schemes presented so far are not the securest under regular
      flipping attack (RFA) and are completely insecure under majority flipping attack
      (MFA). We propose a scheme by splitting the mutual information and the training
      process to improve the security of neural cryptosystem against flipping attacks.
      Both analytical and simulation results show that the success probability of RFA
      on the proposed scheme can be decreased to the level of brute force attack (BFA)
      and the success probability of MFA still decays exponentially with the weights'
      level L. The synchronization time of the parties also remains polynomial with L.
      Moreover, we analyze the security under an advanced flipping attack.

PMID- 15714607
TI  - A neural network model with feature selection for Korean speech act
      classification.
AB  - A speech act is a linguistic action intended by a speaker. Speech act
      classification is an essential part of a dialogue understanding system because
      the speech act of an utterance is closely tied with the user's intention in the
      utterance. We propose a neural network model for Korean speech act
      classification. In addition, we propose a method that extracts morphological
      features from surface utterances and selects effective ones among the
      morphological features. Using the feature selection method, the proposed neural
      network can partially increase precision and decrease training time. In the
      experiment, the proposed neural network showed better results than other models
      using comparatively high-level linguistic features. Based on the experimental
      result, we believe that the proposed neural network model is suitable for real
      field applications because it is easy to expand the neural network model into
      other domains. Moreover, we found that neural networks can be useful in speech
      act classification if we can convert surface sentences into vectors with fixed
      dimensions by using an effective feature selection method.

PMID- 15714609
TI  - [Abstracts of the 5th Annual meeting of the French Society of Neurology. Paris,
      France, 14 January 2005].

PMID- 15714608
TI  - Abstracts of the 94th Annual Meeting of the United States and Canadian Academy of
      Pathology. February 26-March 4, 2005. San Antonio, Texas, USA.

PMID- 15714610
TI  - Elephants, ecology, and nonequilibrium?

PMID- 15714611
TI  - Our health infrastructure.

PMID- 15714612
TI  - American Diabetes Association. Resource guide 2005.

PMID- 15714613
TI  - Inhaled insulin preferred.

PMID- 15714614
TI  - American Diabetes Association. Resource guide 2005. New products.

PMID- 15714615
TI  - American Diabetes Association. Resource guide 2005. Class action: type 2 pills
      update.
AB  - There are now five classes of diabetes pills and several combination oral meds as
      well. Each has a different way of helping you control your diabetes.

PMID- 15714616
TI  - American Diabetes Association. Resource guide 2005. Insulin.
AB  - There are many different insulins for many different situations and lifestyles.
      This section should help you and your doctor decide which insulin or insulins are
      best for you.

PMID- 15714617
TI  - American Diabetes Association. Resource guide 2005. Insulin delivery.
AB  - Syringes...pumps...jet injectors...pens...infusers...they all do the same basic
      thing--deliver insulin. These items carry insulin through the outermost layer of
      skin and into fatty tissue so it can be used by the body. This section will also
      cover injection aids, products design to make injecting easier.

PMID- 15714618
TI  - American Diabetes Association. Resource guide 2005. Blood glucose meters and data
      management system.
AB  - Before you buy a blood glucose meter (also known as a blood glucose monitor),
      check with your doctor and diabetes educator. Make sure the one you choose is
      well suited to your particular needs. You might want to have one at home and one
      for use at school or the office.

PMID- 15714619
TI  - Syndromic surveillance. Reports from a national conference, 2003.

PMID- 15714620
TI  - What is syndromic surveillance?
AB  - Innovative electronic surveillance systems are being developed to improve early
      detection of outbreaks attributable to biologic terrorism or other causes. A
      review of the rationale, goals, definitions, and realistic expectations for these
      surveillance systems is a crucial first step toward establishing a framework for
      further research and development in this area. This commentary provides such a
      review for current syndromic surveillance systems. Syndromic surveillance has
      been used for early detection of outbreaks, to follow the size, spread, and tempo
      of outbreaks, to monitor disease trends, and to provide reassurance that an
      outbreak has not occurred. Syndromic surveillance systems seek to use existing
      health data in real time to provide immediate analysis and feedback to those
      charged with investigation and follow-up of potential outbreaks. Optimal syndrome
      definitions for continuous monitoring and specific data sources best suited to
      outbreak surveillance for specific diseases have not been determined. Broadly
      applicable signal-detection methodologies and response protocols that would
      maximize detection while preserving scant resources are being sought.
      Stakeholders need to understand the advantages and limitations of syndromic
      surveillance systems. Syndromic surveillance systems might enhance collaboration
      among public health agencies, health-care providers, information-system
      professionals, academic investigators, and industry. However, syndromic
      surveillance does not replace traditional public health surveillance, nor does it
      substitute for direct physician reporting of unusual or suspect cases of public
      health importance.

PMID- 15714621
TI  - Review of the 2003 National Syndromic Surveillance Conference--lessons learned
      and questions to be answered.
AB  - Syndromic surveillance is a rapidly evolving field within public health practice.
      Substantial experience has been gained in learning how to conduct syndromic
      surveillance, informed by a growing body of research and practice, including
      refinement of surveillance methods, development of new tools for analysis and
      evaluation, findings from statistical models and applied evaluations, and
      expansion of syndromic surveillance to uses beyond preparedness for biologic
      terrorism. Despite these advances, additional evaluation is needed to help health
      departments determine whether to conduct syndromic surveillance. This paper
      summarizes the lessons learned from the 2003 National Conference on Syndromic
      Surveillance, which provided a foundation for defining a research and evaluation
      agenda and for developing preliminary guidance for public health agencies
      planning to implement syndromic surveillance.

PMID- 15714622
TI  - New York City syndromic surveillance systems.
AB  - New York City's first syndromic surveillance systems were established in 1995 to
      detect outbreaks of waterborne illness. In 1998, daily monitoring of ambulance
      dispatch calls for influenza-like illness began. After the 2001 World Trade
      Center attacks, concern about biologic terrorism led to the development of
      surveillance systems to track chief complaints of patients reporting to emergency
      departments, over-the-counter and prescription pharmacy sales, and worker
      absenteeism. These systems have proved useful for detecting substantial citywide
      increases in common viral illnesses (e.g., influenza, norovirus, and rotavirus).
      However, the systems have not detected more contained outbreaks earlier than
      traditional surveillance. Future plans include monitoring school health and
      outpatient clinic visits, augmenting laboratory testing to confirm syndromic
      signals, and conducting evaluation studies to identify which of these systems
      will be continued for the long term.

PMID- 15714623
TI  - Syndrome and outbreak detection using chief-complaint data--experience of the
      Real-Time Outbreak and Disease Surveillance project.
AB  - This paper summarizes the experience of the Real-Time Outbreak and Disease
      Surveillance (RODS) project in collecting and analyzing free-text emergency
      department (ED) chief complaints. The technical approach involves real-time
      transmission of chief-complaint data as Health Level 7 messages from hospitals to
      a regional data center, where a Bayesian text classifier assigns each chief
      complaint to one of eight syndrome categories. Time-series algorithms analyze the
      syndrome data and generate alerts. Authorized public health users review the
      syndrome data by using Internet interfaces with timelines and maps. Deployments
      in Pennsylvania, Utah, Atlantic City, and Ohio have demonstrated feasibility of
      real-time collection of chief complaints. Retrospective experiments that measured
      case-classification accuracy demonstrated that the Bayesian classifier can
      discriminate between different syndrome presentations. Retrospective experiments
      that measured outbreak-detection accuracy determined that the classifier's
      performance was adequate to support accurate and timely detection of seasonal
      disease outbreaks. Prospective evaluation revealed that a cluster of carbon
      monoxide exposures was detected by RODS within 4 hours of the presentation of the
      first case to an emergency department.

PMID- 15714624
TI  - Removing a barrier to computer-based outbreak and disease surveillance--the RODS
      Open Source Project.
AB  - INTRODUCTION: Computer-based outbreak and disease surveillance requires high
      quality software that is well-supported and affordable. Developing software in an
      open-source framework, which entails free distribution and use of software and
      continuous, community-based software development, can produce software with such
      characteristics, and can do so rapidly. OBJECTIVES: The objective of the Real
      Time Outbreak and Disease Surveillance (RODS) Open Source Project is to
      accelerate the deployment of computer-based outbreak and disease surveillance
      systems by writing software and catalyzing the formation of a community of users,
      developers, consultants, and scientists who support its use. METHODS: The
      University of Pittsburgh seeded the Open Source Project by releasing the RODS
      software under the GNU General Public License. An infrastructure was created,
      consisting of a website, mailing lists for developers and users, designated
      software developers, and shared code-development tools. These resources are
      intended to encourage growth of the Open Source Project community. Progress is
      measured by assessing website usage, number of software downloads, number of
      inquiries, number of system deployments, and number of new features or modules
      added to the code base. RESULTS: During September--November 2003, users generated
      5,370 page views of the project website, 59 software downloads, 20 inquiries, one
      new deployment, and addition of four features. CONCLUSIONS: Thus far, health
      departments and companies have been more interested in using the software as is
      than in customizing or developing new features. The RODS laboratory anticipates
      that after initial installation has been completed, health departments and
      companies will begin to customize the software and contribute their enhancements
      to the public code base.

PMID- 15714625
TI  - National Retail Data Monitor for public health surveillance.
AB  - The National Retail Data Monitor (NRDM) is a public health surveillance tool that
      collects and analyzes daily sales data for over-the-counter (OTC) health-care
      products. NRDM collects sales data for selected OTC health-care products in near
      real time from >15,000 retail stores and makes them available to public health
      officials. NRDM is one of the first examples of a national data utility for
      public health surveillance that collects, redistributes, and analyzes daily sales
      volume data of selected health-care products, thereby reducing the effort for
      both data providers and health departments.

PMID- 15714626
TI  - National Bioterrorism Syndromic Surveillance Demonstration Program.
AB  - The National Bioterrorism Syndromic Surveillance Demonstration Program identifies
      new cases of illness from electronic ambulatory patient records. Its goals are to
      use data from health plans and practice groups to detect localized outbreaks and
      to facilitate rapid public health follow-up. Data are extracted nightly on
      patient encounters occurring during the previous 24 hours. Visits or calls with
      diagnostic codes corresponding to syndromes of interest are counted; repeat
      encounters are excluded. Daily counts of syndromes by zip code are sent to a
      central data repository, where they are statistically analyzed for unusual
      clustering by using a model-adjusted SaTScan approach. The results and raw data
      are displayed on a restricted website. Patient-level information stays at the
      originating health-care organization unless required by public health
      authorities. If a cluster surpasses a threshold of statistical aberration chosen
      by the corresponding public health department, an electronic alert can be sent to
      that department. The health department might then call a clinical responder, who
      has electronic access to records of cases contributing to clusters. The system is
      flexible, allowing for changes in participating organizations, syndrome
      definitions, and alert thresholds. It is transparent to clinicians and has been
      accepted by the health-care organizations that provide the data. The system's
      data are usable by local and national health agencies. Its software is compatible
      with commonly used systems and software and is mostly open-source. Ongoing
      activities include evaluating the system's ability to detect naturally occurring
      outbreaks and simulated terrorism events, automating and testing alerts and
      response capability, and evaluating alternative data sources.

PMID- 15714627
TI  - Daily Emergency Department Surveillance  System --- Bergen County, New Jersey.
AB  - The purpose of the Daily Emergency Department Surveillance System (DEDSS) is to
      provide consistent, timely, and robust data that can be used to guide public
      health activities in Bergen County, New Jersey. DEDSS collects data on all
      emergency department visits in four hospitals in Bergen County and analyzes them
      for aberrant patterns of disease or single instances of certain diseases or
      syndromes. The system monitors for clusters of patients with syndromes consistent
      with the prodrome of a terrorism-related illness (e.g., anthrax or smallpox) or
      naturally occurring disease (e.g., pandemic influenza or food and waterborne
      outbreaks). The health department can use these data to track and characterize
      the temporal and geographic spread of a known outbreak or demonstrate the absence
      of cases during the same period (e.g., severe acute respiratory syndrome [SARS]
      or anthrax). DEDSS was designed to be flexible and readily adaptable as local,
      state, or federal surveillance needs evolve.

PMID- 15714628
TI  - Hospital admissions syndromic surveillance--Connecticut, September 200-November
      2003.
AB  - On September 11, 2001, the Connecticut Department of Public Health (CDPH)
      initiated daily, statewide syndromic surveillance based on unscheduled hospital
      admissions (HASS). The system's objectives were to monitor for outbreaks caused
      by Category A biologic agents and evaluate limits in space and time of identified
      outbreaks. Thirty-two acute-care hospitals were required to report their previous
      day's unscheduled admissions for 11 syndromes (pneumonia, hemoptysis, respiratory
      distress, acute neurologic illness, nontraumatic paralysis, sepsis and
      nontraumatic shock, fever with rash, fever of unknown cause, acute
      gastrointestinal illness, and possible cutaneous anthrax, and suspected illness
      clusters). Admissions for pneumonia, gastrointestinal illness, and sepsis were
      reported most frequently; admissions for fever with rash, possible cutaneous
      anthrax, and hemoptysis were rare. A method for determining the difference
      between random and systemic variation was used to identify differences of >/=3
      standard deviations for each syndrome from a 6-month moving average. HASS was
      adapted to meet changing surveillance needs (e.g., surveillance for anthrax,
      smallpox, and severe acute respiratory syndrome). HASS was sensitive enough to
      reflect annual increases in hospital-admission rates for pneumonia during the
      influenza season and to confirm an outbreak of gastrointestinal illness. Follow
      up of HASS neurologic-admissions reports has led to diagnosis of West Nile virus
      encephalitis cases. Report validation, syndrome-criteria standardization among
      hospitals, and expanded use of outbreak-detection algorithms will enhance the
      system's usefulness.

PMID- 15714629
TI  - BioSense--a national initiative for early detection and quantification of public
      health emergencies.
AB  - BioSense is a national initiative to enhance the nation's capability to rapidly
      detect, quantify, and localize public health emergencies, particularly biologic
      terrorism, by accessing and analyzing diagnostic and prediagnostic health data.
      BioSense will establish near real-time electronic transmission of data to local,
      state, and federal public health agencies from national, regional, and local
      health data sources (e.g., clinical laboratories, hospital systems, ambulatory
      care sites, health plans, U.S. Department of Defense and Veterans Administration
      medical treatment facilities, and pharmacy chains).

PMID- 15714630
TI  - Syndromic surveillance at hospital emergency departments--southeastern Virginia.
AB  - Hospital emergency department (ED) syndromic surveillance has been proposed for
      early detection of a large-scale biologic terrorist attack. However, questions
      remain regarding its usefulness. The authors examined the use of active syndromic
      surveillance at hospital EDs in Virginia for early detection of disease events
      and analyzed the effectiveness of the cumulative sum (CUSUM) algorithm in
      identifying disease events from syndromic data. Daily chief-complaint data were
      collected for 10 months at seven hospital EDs in southeastern Virginia. Data were
      categorized into seven syndromes (fever, respiratory distress, vomiting,
      diarrhea, rash, disorientation, and sepsis), and the CUSUM algorithm was used to
      detect anomalies in each of the seven syndromes at each hospital. Fever and
      respiratory distress syndromes exhibited monthly and ambient-temperature-specific
      trends consistent with southeastern Virginia's influenza season. Furthermore,
      preliminary frequencies of hospital ED patient chief complaints in southeastern
      Virginia during a 10-month period were produced by using syndromic data. This
      system represents an example of a local syndromic surveillance program serving
      multiple cities in a limited geographic region.

PMID- 15714631
TI  - Bivariate method for spatio-temporal syndromic surveillance.
AB  - INTRODUCTION: Statistical analysis of syndromic data has typically focused on
      univariate test statistics for spatial, temporal, or spatio-temporal
      surveillance. However, this approach does not take full advantage of the
      information available in the data. OBJECTIVES: A bivariate method is proposed
      that uses both temporal and spatial data information. METHODS: Using upper
      respiratory syndromic data from an eastern Massachusetts health-care provider,
      this paper illustrates a bivariate method and examines the power of this method
      to detect simulated clusters. RESULTS: Use of the bivariate method increases
      detection power. CONCLUSIONS: Syndromic surveillance systems should use all
      available information, including both spatial and temporal information.

PMID- 15714632
TI  - Role of data aggregation in biosurveillance detection strategies with
      applications from ESSENCE.
AB  - INTRODUCTION: Syndromic surveillance systems are used to monitor daily electronic
      data streams for anomalous counts of features of varying specificity. The
      monitored quantities might be counts of clinical diagnoses, sales of over-the
      counter influenza remedies, school absenteeism among a given age group, and so
      forth. Basic data-aggregation decisions for these systems include determining
      which records to count and how to group them in space and time. OBJECTIVES: This
      paper discusses the application of spatial and temporal data-aggregation
      strategies for multiple data streams to alerting algorithms appropriate to the
      surveillance region and public health threat of interest. Such a strategy was
      applied and evaluated for a complex, authentic, multisource, multiregion
      environment, including >2 years of data records from a system-evaluation exercise
      for the Defense Advanced Research Project Agency (DARPA). METHODS: Multivariate
      and multiple univariate statistical process control methods were adapted and
      applied to the DARPA data collection. Comparative parametric analyses based on
      temporal aggregation were used to optimize the performance of these algorithms
      for timely detection of a set of outbreaks identified in the data by a team of
      epidemiologists. RESULTS: The sensitivity and timeliness of the most promising
      detection methods were tested at empirically calculated thresholds corresponding
      to multiple practical false-alert rates. Even at the strictest false-alert rate,
      all but one of the outbreaks were detected by the best method, and the best
      methods achieved a 1-day median time before alert over the set of test outbreaks.
      CONCLUSIONS: These results indicate that a biosurveillance system can provide a
      substantial alerting-timeliness advantage over traditional public health
      monitoring for certain outbreaks. Comparative analyses of individual algorithm
      results indicate further achievable improvement in sensitivity and specificity.

PMID- 15714633
TI  - Scan statistics for temporal surveillance for biologic terrorism.
AB  - INTRODUCTION: Intentional releases of biologic agents are often designed to
      maximize casualties before diagnostic detection. To provide earlier warning,
      syndromic surveillance requires statistical methods that are sensitive to an
      abrupt increase in syndromes or symptoms associated with such an attack.
      OBJECTIVES: This study compared two different statistical methods for detecting a
      relatively abrupt increase in incidence. The methods were based on the number of
      observations in a moving time window. METHODS: One class of surveillance
      techniques generates a signal based on values of the generalized likelihood ratio
      test (GLRT). This surveillance method is relatively well-known and requires
      simulation, but it is flexible and, by construction, has the appropriate type I
      error. An alternative surveillance method generates a signal based on the p
      values for the conventional scan statistic. This test does not require
      simulation, complicated formulas, or use of specialized software, but it is based
      on approximations and thus can overstate or understate the probability of
      interest. RESULTS: This study compared statistical methods by using brucellosis
      data collected by CDC. The methods provided qualitatively similar results.
      CONCLUSIONS: Relatively simple modification of existing software should be
      considered so that when GLRTs are performed, the appropriate function will be
      maximized. When a health department has data that indicate an unexpected increase
      in rates but its staff lack experience with existing software for surveillance
      based on GLRTs, alternative methods that only require computing Poisson
      probabilities can be used.

PMID- 15714634
TI  - Approaches to syndromic surveillance when data consist of small regional counts.
AB  - INTRODUCTION: Statistical systems designed for syndromic surveillance often must
      be able to monitor data received simultaneously from multiple regions. Such data
      might be of limited size, which would eliminate the possibility of using more
      common surveillance methods that assume data from a normal distribution.
      OBJECTIVES: The objectives of this study were to design and illustrate a
      multiregional surveillance system based on data inputs consisting of small
      regional counts, where frequencies are typically on the order of </=5. METHODS:
      Cumulative sum (CUSUM) methods designed for cumulating the sum of the deviations
      between observed and expected Poisson-distributed data were modified to account
      for changing expectations over time, including weekly and monthly effects. Data
      on lower respiratory tract infections during 1996-1999 at multiple Boston clinics
      among residents from 287 census tracts were used to illustrate the approach.
      RESULTS: When each region was monitored, 19% of the census tracts signaled a
      departure during 1999 from the base period (1996-1998) rates. When local
      statistics were used to monitor tracts and neighborhoods consisting of
      surrounding tracts, 60% of tracts experienced departures during 1999 from the
      base period. These results imply that the increases in lower respiratory tract
      infection that occurred during 1999 were geographically pervasive. CONCLUSIONS:
      Poisson CUSUM methods are useful for monitoring small regional counts over time.
      The methods can be generalized to account for time-varying expectations in the
      counts.

PMID- 15714635
TI  - Algorithm for statistical detection of peaks--syndromic surveillance system for
      the Athens 2004 Olympic Games.
AB  - INTRODUCTION: No generally accepted procedure exists for detecting outbreaks in
      syndromic time series used in the surveillance of natural epidemics or biologic
      attacks. OBJECTIVES: This report evaluates the usefulness for syndromic
      surveillance of the Pulsar approach, which is based on removing long-term trends
      from an observed series and identifying peaks in the residual series of
      surveillance data with cutoffs determined by using a combination of peak height
      and width. METHODS: Simulations were performed to evaluate the Pulsar method and
      compare it with other approaches. The daily syndromic counts in emergency
      departments of four major hospitals in the Athens area during August 2002-August
      2003 were analyzed for two common syndromes. A standardized residual series was
      generated by omitting trends and noise in the original data series; this series
      was examined for the presence of peaks (i.e., points having magnitude higher than
      at least one of three probabilistically determined cutoffs). The whole process
      was iterated, and the baseline was recalculated by assigning reduced weight to
      the identified peaks. RESULTS: For the specific simulation schema used, the
      Pulsar method fared well when compared with other approaches in meeting the
      performance criteria of sensitivity, specificity, and timeliness. CONCLUSIONS:
      Although the suggested algorithm needs further validation regarding the
      correspondence between detected peaks and true biologic alerts, the Pulsar
      technique appears effective for observing peaks in time series of syndromic
      events. The simplicity of the algorithm, its ability to detect peaks based not
      only on height but also on width, and its performance in the simulated data sets
      make it a promising candidate for further use in syndromic surveillance.

PMID- 15714636
TI  - Taming variability in free text: application to health surveillance.
AB  - INTRODUCTION: Use of free text in syndromic surveillance requires managing the
      substantial word variation that results from use of synonyms, abbreviations,
      acronyms, truncations, concatenations, misspellings, and typographic errors.
      Failure to detect these variations results in missed cases, and traditional
      methods for capturing these variations require ongoing, labor-intensive
      maintenance. OBJECTIVES: This paper examines the problem of word variation in
      chief-complaint data and explores three semi-automated approaches for addressing
      it. METHODS: Approximately 6 million chief complaints from patients reporting to
      emergency departments at 54 hospitals were analyzed. A method of text
      normalization that models the similarities between words was developed to manage
      the linguistic variability in chief complaints. Three approaches based on this
      method were investigated: 1) automated correction of spelling and typographical
      errors; 2) use of International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) codes to select chief complaints to mine for
      overlooked vocabulary; and 3) identification of overlooked vocabulary by matching
      words that appeared in similar contexts. RESULTS: The prevalence of word errors
      was high. For example, such words as diarrhea, nausea, and vomiting were
      misspelled 11.0%-18.8% of the time. Approximately 20% of all words were
      abbreviations or acronyms whose use varied substantially by site. Two methods,
      use of ICD-9-CM codes to focus searches and the automated pairing of words by
      context, both retrieved relevant but previously unexpected words. Text
      normalization simultaneously reduced the number of false positives and false
      negatives in syndrome classification, compared with commonly used methods based
      on word stems. In approximately 25% of instances, using text normalization to
      detect lower respiratory syndrome would have improved the sensitivity of current
      word-stem approaches by approximately 10%-20%. CONCLUSIONS: Incomplete vocabulary
      and word errors can have a substantial impact on the retrieval performance of
      free-text syndromic surveillance systems. The text normalization methods
      described in this paper can reduce the effects of these problems.

PMID- 15714637
TI  - Comparison of two major emergency department-based free-text chief-complaint
      coding systems.
AB  - INTRODUCTION: Emergency departments (EDs) using free-text chief-complaint data
      for syndromic surveillance face a unique challenge because a complaint might be
      described and coded in multiple ways. OBJECTIVE: Two major ED-based free-text
      chief-complaint coding systems were compared for agreement between free-text
      interpretation and syndrome coding. METHODS: Chief-complaint data from 21,736
      patients at an urban ED were processed through both the New York City Department
      of Health and Mental Hygiene (DOHMH) syndrome coding system as modified by the
      Chicago Department of Public Health and the Real-Time Outbreak Detection System
      Complaint Coder (CoCo, version 2.1, University of Pittsburgh). To account for
      differences in each system's specified syndromes, relevant syndromes from the
      DOHMH system were collapsed into the corresponding CoCo categories so that a
      descriptive comparison could be made. DOHMH classifications were combined to
      match existing CoCo categories as follows: 1) vomit+diarrhea = Gastrointestinal;
      2) cold+respiratory+asthma = Respiratory; 3) fevflu = Constitutional; 4) rash =
      Rash; 5) sepsis+other = Other, 6) unknown = Unknown. RESULTS: Overall agreement
      between DOHMH and CoCo syndrome coding was optimal (0.614 kappa). However,
      agreement between individual syndromes varied substantially. Rash and Respiratory
      had the highest agreement (0.711 and 0.594 kappa, respectively). Other and
      Constitutional had an intermediate level of agreement (0.453 and 0.419 kappa,
      respectively), but less than optimal agreement was identified for
      Gastrointestinal and Unknown (0.270 and 0.002 kappa, respectively). CONCLUSIONS:
      Although this analysis revealed optimal overall agreement between the two systems
      evaluated, substantial differences in classification schemes existed,
      highlighting the need for a consensus regarding chief-complaint classification.

PMID- 15714638
TI  - How many illnesses does one emergency department visit represent? Using a
      population-based telephone survey to estimate the syndromic multiplier.
AB  - INTRODUCTION: Syndromic surveillance monitors trends in nonspecific health
      indicator data to detect disease outbreaks in a timely manner; however, only a
      limited percentage of persons with mild illness might exhibit behaviors that
      could be detected by syndromic surveillance. OBJECTIVES: The objectives of this
      study were to 1) examine the demographic characteristics of New Yorkers with
      recent flu-like or diarrheal illness, 2) describe behaviors associated with
      having flu-like illness, and 3) estimate the citywide burden for selected
      illnesses by calculating the syndromic multiplier (i.e., the number of citywide
      illnesses represented by each visit to an emergency department [ED]). METHODS: A
      cross-sectional telephone survey of 2,433 adult residents of New York City (NYC)
      was conducted during March 19-March 31, 2003, and October 27-November 23, 2003.
      Respondents were asked about flu-like illness, behaviors related to flu-like
      illness, and diarrheal illness during the 30 days before the interview. Estimated
      numbers of citywide illnesses were compared with ED visits for flu-like and
      diarrheal illnesses that were recorded by the NYC syndromic surveillance system
      for the same periods. RESULTS: Every ED visit for flu-like illness represented
      approximately 60 illnesses among city residents; every visit for diarrheal
      illness represented approximately 251 illnesses. Among adults who reported a
      recent flu-like illness, 53.2% purchased over-the-counter (OTC) medications;
      32.6% reported missing school or work; 29.1% visited a physician; 21.4% called a
      physician for advice; 8.8% visited an ED; and 3.8% called a nurse or health
      hotline for advice. Of those who reported multiple behaviors, respondents most
      commonly reported purchasing OTC medications as their first response to a flu
      like illness. CONCLUSIONS: Population-based survey data can be used in
      conjunction with syndromic surveillance data to better understand the relation
      between nonspecific health indicators and the burden of certain illnesses in the
      community, and to assess the representativeness of different syndromic data
      sources.

PMID- 15714639
TI  - Comparison of office visit and nurse advice hotline data for syndromic
      surveillance--Baltimore-Washington, D.C., metropolitan area, 2002.
AB  - INTRODUCTION: Kaiser Permanente of the Mid-Atlantic States (KPMAS) is
      collaborating with the Electronic Surveillance System for Early Notification of
      Community-Based Epidemics II (ESSENCE II) program to understand how managed-care
      data can be effectively used for syndromic surveillance. OBJECTIVES: This study
      examined whether KPMAS nurse advice hotline data would be able to predict the
      syndrome diagnoses made during subsequent KPMAS office visits. METHODS: All nurse
      advice hotline calls during 2002 that were linked to an outpatient office visit
      were identified. By using International Classification of Diseases, Ninth
      Revision (ICD-9) codes, outpatient visits were categorized into seven ESSENCE II
      syndrome groups (coma, gastrointestinal, respiratory, neurologic, hemorrhagic,
      infectious dermatologic, and fever). Nurse advice hotline calls were categorized
      into ESSENCE II syndrome groups on the basis of the advice guidelines assigned.
      For each syndrome group, the sensitivity, specificity, and positive predictive
      value of hotline calls were calculated by using office visits as a diagnostic
      standard. For matching syndrome call-visit pairs, the lag (i.e., the number of
      hours that elapsed between the date and time the patient spoke to an advice nurse
      and the date and time the patient made an office visit) was calculated. RESULTS:
      Of all syndrome groups, the sensitivity of hotline calls for respiratory syndrome
      was highest (74.7%), followed by hotline calls for gastrointestinal syndrome
      (72.0%). The specificity of all nurse advice syndrome groups ranged from 88.9% to
      99.9%. The mean lag between hotline calls and office visits ranged from 8.3 to 50
      hours, depending on the syndrome group. CONCLUSIONS: The timeliness of hotline
      data capture compared with office visit data capture, as well as the sensitivity
      and specificity of hotline calls for detecting respiratory and gastrointestinal
      syndromes, indicate that KPMAS nurse advice hotline data can be used to predict
      KPMAS syndromic outpatient office visits.

PMID- 15714640
TI  - Progress in understanding and using over-the-counter pharmaceuticals for
      syndromic surveillance.
AB  - INTRODUCTION: Public health researchers are increasingly interested in the
      potential use of monitoring data on over-the-counter (OTC) pharmaceutical sales
      as a source of timely information about community health. However, fundamental
      uncertainties persist, including how timely such information is and how best to
      aggregate information about hundreds of products. OBJECTIVES: This analysis
      provides new information about OTC timeliness and illustrates a method of OTC
      product aggregation for surveillance purposes. METHODS: Timeliness measurements
      were made by correlating pharmaceutical sales counts with counts of physician
      encounters, after adjustment to remove seasonal effects from both counts. OTC
      product aggregations were formed by a two-stage process. In the first stage,
      individual products were placed into small groups based on qualitative
      observations. In the second stage, a clustering algorithm was used to form
      supergroups (i.e., product group clusters) sharing similar sales histories.
      RESULTS: Even after seasonal correction, OTC counts correlated with clinical
      measures of community illness. However, the lead time of nonseasonal fluctuations
      was substantially shorter than that for uncorrected data. The clustering approach
      produced 16 meaningful supergroups containing products that behaved approximately
      alike. CONCLUSIONS: Measurements of OTC lead time sensitive to the timing of
      annual cyclic trends in the behavior of persons seeking health care do not
      reliably indicate the lead time observed for short-term (e. g. weekly or monthly)
      fluctuations in community health-care utilization.

PMID- 15714641
TI  - Evaluation challenges for syndromic surveillance--making incremental progress.
AB  - INTRODUCTION: The 2003 National Syndromic Surveillance Conference provided an
      opportunity to examine challenges and progress in evaluating syndromic
      surveillance systems. OBJECTIVES: Using the conference abstracts as a focus, this
      paper describes the status of performance measurement of syndromic surveillance
      systems and ongoing challenges in system evaluation. METHODS: Ninety-nine
      original abstracts were reviewed and classified descriptively and according to
      their presentation of evaluation attributes. RESULTS: System evaluation was the
      primary focus of 35% of the abstracts submitted. Of those abstracts, 63%
      referenced prospective evaluation methods and 57% reported on outbreak detection.
      However, no data were provided in 34% of the evaluation abstracts, and only 37%
      referred to system signals, 20% to investigation of system signals, and 20% to
      timeliness. CONCLUSIONS: Although this abstract review is not representative of
      all current syndromic surveillance efforts, it highlights recent attention to
      evaluation and the need for a basic set of system performance measures. It also
      proposes questions to be answered of all public health systems used for outbreak
      detection.

PMID- 15714642
TI  - Measuring outbreak-detection performance by using controlled feature set
      simulations.
AB  - INTRODUCTION: The outbreak-detection performance of a syndromic surveillance
      system can be measured in terms of its ability to detect signal (i.e., disease
      outbreak) against background noise (i.e., normally varying baseline disease in
      the region). Such benchmarking requires training and the use of validation data
      sets. Because only a limited number of persons have been infected with agents of
      biologic terrorism, data are generally unavailable, and simulation is necessary.
      An approach for evaluation of outbreak-detection algorithms was developed that
      uses semisynthetic data sets to provide real background (which effectively
      becomes the noise in the signal-to-noise problem) with artificially injected
      signal. The injected signal is defined by a controlled feature set of variable
      parameters, including size, shape, and duration. OBJECTIVES: This report defines
      a flexible approach to evaluating public health surveillance systems for early
      detection of outbreaks and provides examples of its use. METHODS: The stages of
      outbreak detection are described, followed by the procedure for creating data
      sets for benchmarking performance. Approaches to setting parameters for simulated
      outbreaks by using controlled feature sets are detailed, and metrics for
      detection performance are proposed. Finally, a series of experiments using
      semisynthetic data sets with artificially introduced outbreaks defined with
      controlled feature sets is reviewed. RESULTS: These experiments indicate the
      flexibility of controlled feature set simulation for evaluating outbreak
      detection sensitivity and specificity, optimizing attributes of detection
      algorithms (e.g., temporal windows), choosing approaches to syndrome groupings,
      and determining best strategies for integrating data from multiple sources.
      CONCLUSIONS: The use of semisynthetic data sets containing authentic baseline and
      simulated outbreaks defined by a controlled feature set provides a valuable means
      for benchmarking the detection performance of syndromic surveillance systems.

PMID- 15714643
TI  - Evaluation of syndromic surveillance systems--design of an epidemic simulation
      model.
AB  - INTRODUCTION: The paucity of outbreak data from biologic terrorism and emerging
      infectious diseases limits the evaluation of syndromic surveillance systems.
      Evaluation using naturally occurring outbreaks of proxy disease (e.g., influenza)
      is one alternative but does not allow for rigorous evaluation. Another approach
      is to inject simulated outbreaks into real background data, but existing
      simulation models generally do not account for such factors as spatial mobility
      and do not explicitly incorporate knowledge of the disease agent. OBJECTIVE: The
      objective of this analysis was to design a simulated anthrax epidemic injection
      model that accounts for the complexity of the background data and enables
      sensitivity analyses based on uncertain disease-agent characteristics. MODEL
      REQUIREMENTS AND ASSUMPTIONS: Model requirements are described and used to limit
      the scope of model development. Major assumptions used to limit model complexity
      are also described. Available literature on inhalational anthrax is reviewed to
      ensure that the level of model detail reflects available disease knowledge. MODEL
      DESIGN: The model is divided into four components: 1) agent dispersion, 2)
      infection, 3) disease and behavior, and 4) data source. The agent-dispersion
      component uses a Gaussian plume model to compute spore counts on a fine grid. The
      infection component uses a cohort approach to identify infected persons by
      residential zip code, accounting for demographic covariates and spatial mobility.
      The disease and behavior component uses a discrete-event approach to simulate
      progression through disease stages and health-services utilization. The data
      source component generates records to insert into background data sources.
      CONCLUSIONS: An epidemic simulation model was designed to enable evaluation of
      syndromic surveillance systems. The model addresses limitations of existing
      simulation approaches by accounting for such factors as spatial mobility and by
      explicitly modeling disease knowledge. Subsequent work entails software
      implementation and model validation.

PMID- 15714644
TI  - Benchmark data and power calculations for evaluating disease outbreak detection
      methods.
AB  - INTRODUCTION: Early detection of disease outbreaks enables public health
      officials to implement immediate disease control and prevention measures.
      Computer-based syndromic surveillance systems are being implemented to complement
      reporting by physicians and other health-care professionals to improve the
      timeliness of disease-outbreak detection. Space-time disease-surveillance methods
      have been proposed as a supplement to purely temporal statistical methods for
      outbreak detection to detect localized outbreaks before they spread to larger
      regions. OBJECTIVE: The aims of this study were twofold: 1) to design and make
      available benchmark data sets for evaluating the statistical power of space-time
      early detection methods and 2) to evaluate the power of the prospective purely
      temporal and space-time scan statistics by applying them to the benchmark data
      sets at different parameter settings. METHODS: Simulated data sets based on the
      geography and population of New York City were created, including effects of
      outbreaks of varying size and location. Data sets with no outbreak effects were
      also created. Scan statistics were then run on these data sets, and the resulting
      power performances were analyzed and compared. RESULTS: The prospective space
      time scan statistic performs well for a spectrum of outbreak models. By
      comparison, the prospective purely temporal scan statistic has higher power for
      detecting citywide outbreaks but lower power for detecting geographically
      localized outbreaks. CONCLUSIONS: The benchmark data sets created for this study
      can be used successfully for formal statistical power evaluations and
      comparisons. If an anomaly caused by an outbreak is local, purely temporal
      surveillance methods might be unable to detect it, in which case space-time
      methods would be necessary for early detection.

PMID- 15714645
TI  - Bio-ALIRT biosurveillance detection algorithm evaluation.
AB  - INTRODUCTION: Early detection of disease outbreaks by a medical biosurveillance
      system relies on two major components: 1) the contribution of early and reliable
      data sources and 2) the sensitivity, specificity, and timeliness of
      biosurveillance detection algorithms. This paper describes an effort to assess
      leading detection algorithms by arranging a common challenge problem and
      providing a common data set. OBJECTIVES: The objectives of this study were to
      determine whether automated detection algorithms can reliably and quickly
      identify the onset of natural disease outbreaks that are surrogates for possible
      terrorist pathogen releases, and do so at acceptable false-alert rates (e.g.,
      once every 2-6 weeks). METHODS: Historic de-identified data were obtained from
      five metropolitan areas over 23 months; these data included International
      Classification of Diseases, Ninth Revision (ICD-9) codes related to respiratory
      and gastrointestinal illness syndromes. An outbreak detection group identified
      and labeled two natural disease outbreaks in these data and provided them to
      analysts for training of detection algorithms. All outbreaks in the remaining
      test data were identified but not revealed to the detection groups until after
      their analyses. The algorithms established a probability of outbreak for each
      day's counts. The probability of outbreak was assessed as an "actual" alert for
      different false-alert rates. RESULTS: The best algorithms were able to detect all
      of the outbreaks at false-alert rates of one every 2-6 weeks. They were often
      able to detect for the same day human investigators had identified as the true
      start of the outbreak. CONCLUSIONS: Because minimal data exists for an actual
      biologic attack, determining how quickly an algorithm might detect such an attack
      is difficult. However, application of these algorithms in combination with other
      data-analysis methods to historic outbreak data indicates that biosurveillance
      techniques for analyzing syndrome counts can rapidly detect seasonal respiratory
      and gastrointestinal illness outbreaks. Further research is needed to assess the
      value of electronic data sources for predictive detection. In addition,
      simulations need to be developed and implemented to better characterize the size
      and type of biologic attack that can be detected by current methods by
      challenging them under different projected operational conditions.

PMID- 15714646
TI  - ESSENCE II and the framework for evaluating syndromic surveillance systems.
AB  - INTRODUCTION: The Electronic Surveillance System for the Early Notification of
      Community-Based Epidemics (ESSENCE II) is a prototype syndromic surveillance
      system for capturing and analyzing public health indicators for early detection
      of disease outbreaks. OBJECTIVES: This paper presents a preliminary evaluation of
      ESSENCE II according to a CDC framework for evaluating syndromic surveillance
      systems. METHODS: Each major topic of the framework is addressed in this
      assessment of ESSENCE II performance. RESULTS: ESSENCE captures data in multiple
      formats, parses text strings into syndrome groupings, and applies multiple
      temporal and spatio-temporal outbreak-detection algorithms. During a recent DARPA
      evaluation exercise, ESSENCE algorithms detected a set of health events with a
      median delay of 1 day after the earliest possible detection opportunity.
      CONCLUSIONS: ESSENCE II has provided excellent performance with respect to the
      framework and has proven to be a useful and cost-effective approach for providing
      early detection of health events.

PMID- 15714647
TI  - Conducting population behavioral health surveillance by using automated
      diagnostic and pharmacy data systems.
AB  - INTRODUCTION: The Walter Reed Army Institute of Research used the Electronic
      Surveillance System for the Early Notification of Community-Based Epidemics
      (ESSENCE) to conduct population-based behavioral health surveillance among
      military-health-system beneficiaries. The study analyzed the effectiveness of
      using prescribing patterns of psychotropic medications to monitor changes in a
      community's behavioral health status. OBJECTIVES: The objectives of this study
      were to 1) determine the feasibility of tracking psychiatric illnesses by
      monitoring prescriptions for psychiatric medications; 2) assess how often
      psychiatric medications are prescribed for patients with no record of psychiatric
      illness; 3) determine at what types of clinics these medications are prescribed
      most often and what other diagnoses are attributed to these patients; and 4)
      analyze data for potential changes in the population's mental health after high
      stress events. METHODS: Correlation analysis and calculations of sensitivity and
      specificity were used to determine how well prescription medications correlate
      with outpatient diagnoses and how well they serve as proxies for outpatient
      diagnoses. A descriptive analysis was conducted of the types of clinics (e.g.,
      primary care, behavioral health, or other specialty clinics) treating patients
      and the associated percentage of concurrence between prescriptions and diagnostic
      codes. RESULTS: In military treatment facilities, a diagnosis of depression or
      anxiety correlated significantly (r = 0.82) with antidepressant or anxiolytic
      prescriptions. Sensitivity of prescriptions when compared with outpatient visits
      was 0.76, and specificity was 0.94. Among those patients who visited a primary
      care clinic either the day before or the same day as an antidepressant or
      anxiolytic prescription was filled, 60.1% did not receive a diagnosis of any
      mental health disorder. Behavioral health clinics had the highest correlation
      between diagnoses and prescriptions; specialty clinics had the lowest.
      CONCLUSIONS: Behavioral health trends in a population can be monitored by
      automated analysis of prescribing patterns alone. This method might be a rapid
      indicator of needed mental health interventions after acute stress-inducing
      events and be more sensitive than tracking diagnoses alone.

PMID- 15714648
TI  - Evaluation of an electronic general-practitioner-based syndromic surveillance
      system--Auckland, New Zealand, 2000-2001.
AB  - INTRODUCTION: During 2000 and 2001, Auckland Regional Public Health Service
      piloted a general-practitioner-based syndromic surveillance system (GPSURV).
      OBJECTIVES: The pilot evaluated data capture, the method used to distinguish
      initial from follow-up visits, the definition of denominators, and the external
      validity of measured influenza-like illness trends. METHODS: GPSURV monitored
      three acute infectious-disease syndromes: gastroenteritis, influenza-like
      illness, and skin and subcutaneous tissue infection. Standardized terms were used
      to describe the syndromes. Data were uploaded daily from clinics and transferred
      to a database via a secure network after one-way encryption of patient
      identifiers. Records were matched to allow the distinction of follow-ups from
      first visits, based on between-visit intervals of </=8 weeks. Denominator
      populations were based on counts of unique patients treated at participating
      clinics during the previous 2 years. Record completion was examined by using
      before-and-after surveys of self-assessed standardized-term recording. Between
      visit intervals were counted for matching records and alternative denominators
      were calculated on the basis of different observation periods. Weekly influenza
      like illness rates were compared with rates generated by an alternative system.
      RESULTS: Physicians' self-reported recording compliance was highest for skin and
      subcutaneous tissue infection (71%) and lowest for influenza-like illness (48%).
      Initial visits had 18%-19% greater compliance than follow-up visits. The number
      of physicians reporting increasing compliance during the pilot was greater than
      the number reporting decreases for all conditions. Comparison of data with an
      independent influenza-like illness surveillance system indicated a close
      agreement between the two data series. CONCLUSIONS: These results indicate that
      incidence of acute syndromes can be monitored, at least as successfully as a
      manual system, by using standardized clinical-term data from selected general
      practice clinics. The provision of feedback reports appears to have a limited but
      positive effect on data quality.

PMID- 15714649
TI  - Practice brief. Redisclosure of patient health information.

PMID- 15714650
TI  - Information from your family doctor. Alcoholism--what should I know about it?

PMID- 15714651
TI  - Information from your family doctor. Constipation.

PMID- 15714652
TI  - Information from your family doctor. Irritable bowel syndrome.

PMID- 15714653
TI  - Information from your family doctor. Inflammatory bowel disease.

PMID- 15714654
TI  - [Discussion of professionalism: more than just academic knowledge].

PMID- 15714655
TI  - [Political dialogue about school reform for nursing occupations: from model to
      routine availability].

PMID- 15714656
TI  - [Consensus regarding hormone replacement therapy during menopause].

PMID- 15714657
TI  - [Update on current care guidelines. Diagnostics and follow-up of breast cancers].

PMID- 15714658
TI  - Death of Seurat.

PMID- 15714659
TI  - SARS-CoV sampling from 3 portals.

PMID- 15714660
TI  - Occupational health response to SARS.

PMID- 15714661
TI  - Tracing SARS-coronavirus variant with large genomic deletion.

PMID- 15714662
TI  - Multidrug-resistant Salmonella Java.

PMID- 15714663
TI  - 1990s Vibrio cholerae epidemic, Brazil.

PMID- 15714664
TI  - Fluoroquinolone-resistant Salmonella Paratyphi A.

PMID- 15714665
TI  - Pygmy populations seronegative for Marburg virus.

PMID- 15714666
TI  - Disseminated coccidioidomycosis.

PMID- 15714667
TI  - Kytococcus schroeteri endocarditis.

PMID- 15714668
TI  - Viral gastroenteritis in Mongolian infants.

PMID- 15714669
TI  - Bordetella pertussis isolates, Finland.

PMID- 15714670
TI  - [The most important sources of the Graeco-Arabic medicine].
AB  - The author gives a comprehensive guide to Hungarian scholars, who attempt to
      search the history of Graeco-Arabic medicine and dietetics, respectively. This
      guide contains a short introduction into the different types of sources, lists
      the main authors, editions and texts available in Hungary indicating the
      libraries where the sources are to be found. The author organizes his material
      according the the main authors of the subject. Helped by this useful "database"
      researchers might be able to avoid difficulties of the first steps on this still,
      actually, largely unexplored field of the history of medicine .

PMID- 15714671
TI  - [Ill-conditioned rules on the throne of Byzantium].
AB  - Author presents and analyses informations of non-medical texts of Byzantine
      historians and chroniclers concerning diseases of Byzantine emperors, concluding
      that diseases were implicated in certain political and military difficulties.
      Only one third of the emperors died due to natural causes (i.e. illnesses). Some
      historians, such as Anna Comnena and Michael Psellos had studied medicine, both
      of them had excellent knowledge of medical theories of their times. Some diseases
      in Byzantium were widespread and had high morbidity. This material gives an
      indication that arthritis (resembling gout) tyrannised a great number of
      emperors. Contemporary historians maintain that the main causes of gout were
      overconsumption of alcoholic drinks and food. Other very serious conditions were
      acute and chronic pyelonephritis and urolithiasis. Relatively frequent conditions
      of the emperors included pestilential diseases (dysentery, typhoid fever, etc.),
      psychiatric disorders, epilepsy and arteriosclerosis.

PMID- 15714672
TI  - [The clinic for internal medicine at Szeged headed by Istvan Rusznyak].
AB  - Istvan Rusznyak was one of the most remarkable members of the internist school of
      Baron Sandor Koranyi, whose functional understanding of body processes made his
      school famous. Rusznyak started his career at Szeged where he much improved the
      university internist teaching hospital, originally opened in December 1928, which
      beside healing was a base of medical research and tuition alike. Rusznyak led the
      Clinique as a director until World War Two. In developing of the Clinique it was
      not only Rusznyak's medical expertise and efficiency in organisation which helped
      but also his wide ranger of personal contacts. In spite of the later he was,
      nevertheless, deported. After the war he was appointed the post of director of
      the 1st Clinique of Internal Medicine of the Budapest University. His reputation
      during his years at Budapest, alike in Szeged made him a well known internist and
      an effective director. Among his friends he could count the best Hungarian
      medical experts. The article also touches the rather negative role Rusznyak
      played for the Stalinist regime in Hungary.

PMID- 15714673
TI  - Stephan Kornyey's contribution to the study of encephalitides.
AB  - A considerable part of Kornyey's work deals with the problem of encephalitides.
      HIs interest in this topic was roused by Heinrich Pette and in collaboration they
      studied the histopathology and pathogenesis of experimental and human
      poliomyelitis. On the basis of their findings they advocated the neural spread of
      the poliomyelitis virus. THey described the distribution of the poliovirus within
      the nervous system, its close affinity to the voluntary motor system and analysed
      the influence of the portal of entry and special neurotropism on the development
      of the distribution pattern of the process. THe encephalitic process changes as a
      function of time; the significance of this observation was expressed in the
      concept of the time factor. Kornyey designated the affinity of the poliovirus
      towards the neurons among the cellular components of the nervous tissue as
      gangliocytotropism. Based on his observation, he characterized the features of
      neural spread of virsuses and the selective character of this spread within the
      central nervous system. THe study of two other polioencephalitides with
      predilectional involvement of the brain stem, Borna disease and tickborne
      encephalitis, allowed him further pathogenetic assessments. Kornyey described the
      first manifestation of subacute panencephalitis in the Carpathian basin. He
      devoted special attention to the clinical and neuropathological analysis of
      various forms of leukoencephalomyelitides and closely followed the development of
      the principle of neuro-allergy (Pette) and the change in the pathogenetic view of
      these diseases. His excellent synthesising ability enabled him to write
      comprehensive review articles and textbook chapters on the various aspects of
      encephalitides.

PMID- 15714675
TI  - Lasers in dermatology: two-year experience at University Department of
      Dermatology and Venerology, Zagreb University Hospital Center, Zagreb, Croatia.

PMID- 15714676
TI  - [A survey on the medical past of Szekelykeresztur (Transylvania) and of its
      environment].
AB  - There are few written documents and even fewer accurate data on the public
      hygiene of Szekelykeresztur (today also, as Cristuru Secuesc in Rumania), at the
      remote southern parts of historic Hungary. Ethno-medicine was certainly based on
      oral traditions, and its observations, experience and practice included the
      widespread use of magic and quackmedicine. The repeated epidemics of plague,
      cholera and diphteria - some even occurring in the 20th c. - forced local
      authorities to introduce counter-measures. The number of university trained,
      qualified physicians remained, however, inadequate during mid 19th c. in
      Transylvania: in 1843, there were only 69 of them and though it was levelled up
      to 94 by 1863, but even this increase was less than enough. Despite the devoted
      efforts of the qualified medical staff, medical care in this under-urbanised and
      generally underdeveloped region remained weak. Modern scientific medicine only
      came the 20th c. and set only slowly through, so that in the first decades of the
      20th c. the yearly increase of the Szekely (Szekler) population was between 0 and
      4.9%. The centuries old backwardness of the region, was only slowly overcome.

PMID- 15714677
TI  - [Hermeneutics and diagnostics as shown by the Biblical Samson-stories].
AB  - The author investigates the personality of Samson, the Biblical hero, and
      supposes, that we face in his case some sort of mental illness. He bases his
      conclusions upon the following facts: (1) Samson's strength is abnormal, which
      might be as a result of some sort of brain storm or hysteria. (2) Neither the
      causes, nor the objects of his brain storms could be explained rationally, as his
      deed look quite irrelevant and ill-proportioned. (3) His victims sometimes are
      animals, which might cover sadistic inclination. (4) As a result of his abnormal
      behaviour Samson separates himself from society. Furthermore, at the end of his
      story he falls into total dementia. The author, however, emphasizes the
      impressive fact, that in spite of his mental disorders Samson was able to play
      and important role in the history of his nation - and this fact reflects a quite
      different attitude towards illness, as compared to those what we hold today.

PMID- 15714678
TI  - [The hospitale of the town of Pecs (South-Hungary) in the 14-16. centuries].
AB  - The study collects and presents a list of those persons, who functioned as
      directors (magister hospitalis, rector hospitalis) of the mediaeval hospital at
      Pecs (Quinqueecclesiae or Funkirchen), in the period between the 14th and 16th
      centuries. During this period (1320-1532) altogether 13 such persons could be
      identified. The overwhelming majority (92.3%) held at the same time
      ecclesiastical positions as well. Ten of them were beneficiaries of a canonical
      stallum at the chapter of the Pecs Cathedral. The persons heading the hospital
      worked at the same time as parsons at the city-parish St. Bartholomew. The
      article contains also the biographical data of the directors.

PMID- 15714679
TI  - Hungarian doctors and the "Golden Age" (1884-1914) of Opatija (Croatia).
AB  - At the turn of the 20th century, in the frame of the Austro-Hungarian Monarchy,
      Hungarian enterpreneurs - backed by the Hungarian government - attempted to
      launch a "Hungarian area" on the Adriatic coasts with the center of Crikvenica
      and Abbazia (presently Opatija). (This time Fiume (Rijeka), as the only Hungarian
      seaport has been partly possessed and governed by Hungarians). Author gives a
      short overview on these attempts with a special regard to the activity of
      Hungarian physicians on the Adriatic coasts, especially in Abbazia (Opatija) and
      to the health resorts founded by them, respectively. He calls our attention to
      the fact, that as a result of the activity of Hungarian physicians and
      enterpreneurs this period proved to be the so called "golden age" of Abbazia and
      of its environment.

PMID- 15714680
TI  - Vesiculobullous lesion on the right fifth toe.

PMID- 15714681
TI  - [Dezso Miskolczy, the founder of modern Hungarian neurology].
AB  - The present article gives a short overview on the biography and scientific work
      of professor Dezso Miskolczy, one of the founders of Hungarian neurology. his
      main scientific achievement was the modification of the Bielschowsky-method of
      imprenation. Miskolczy published already in 1926 an article on the problem of the
      crossing of central tracks of nervous system. He search successfully - among
      others - the problems of constitution, inheritance, aging, and the structure of
      the cerebellum as well. Miskolczy worked not only in Budapest, but in Szeged,
      Kolozsvar and Marosvasarhely (Transylvania) too. His activity has been honoured
      with the highest acknowledgements and decorations given by the Hungarian and
      Rumanian governments. He was elested to member of several foreign academies and
      scientific societies. His students - who always honoured and respected him - were
      deeply impressed by his suggestive personality and pedagogical talent.

PMID- 15714682
TI  - [Gerontology in Hungary. A historical view on Hungarian gerontology].
AB  - Hungarian gerontological research has deep roots. Since the publication of the
      first Hungarian treaty on geriatrics in 1692 several works have been published by
      Hungarian scientists. Organised research in the field of gerontology started in
      1954 by the foundation of Gerontological Committee of the Hungarian Academy of
      Sciences. The author summarizes the following landmarks in gerontology:- The set
      up of organizations in the field of gerontology.- The foundation of research
      institutions and their scientific and educational work.- International
      relationships by organizing international congresses in Hungary, offices and
      honours of Hungarian scientists in international organizations.- And finally
      proposals for future development.

PMID- 15714683
TI  - Efforts in 1947 to make Prof. Dr. Ernestus de Balogh (1890-1964) work for the
      University of Istanbul.

PMID- 15714684
TI  - [DIGAMI 2: breaking the spell of insulin for heart infarct. Re the article in DMW
      45/2004].

PMID- 15714685
TI  - What is special about the "human" in "human genetics"?

PMID- 15714687
TI  - 2004 ASHG Award for Excellence in Human Genetics Education. And the band played
      on...

PMID- 15714686
TI  - 2004 William Allan Award address. Cloning of the DMD gene.

PMID- 15714688
TI  - 2004 Curt Stern Award Address. The SNP endgame: a multidisciplinary approach.

PMID- 15714689
TI  - [What is the future of internal medicine in Europe? Will it be apoptosis,
      necrosis or adaptation and remodeling?].

PMID- 15714690
TI  - [History of heart transplantation--short commentary].

PMID- 15714691
TI  - [Do we know when to examine the thyroid gland?].

PMID- 15714692
TI  - Introduction to eukaryotic transcription and chromatin.

PMID- 15714693
TI  - Mitigation and the Americans with Disabilities Act.

PMID- 15714694
TI  - 2004 William Allan Award Address. Introductory speech for Louis Kunk.

PMID- 15714695
TI  - Erratum to "Noise-induced changes of neuronal spontaneous activity in mice
      inferior colliculus brain slices".
AB  - The inferior colliculus (IC) in vivo is reportedly subject to a noise-induced
      decrease of GABA-related inhibitory synaptic transmission accompanied by an
      amplitude increase of auditory evoked responses, a widening of tuning curves and
      a higher neuronal discharge rate at suprathreshold levels. However, other in vivo
      experiments which demonstrated constant neuronal auditory thresholds or unchanged
      spontaneous activity in the IC after noise exposure did not confirm those
      findings. Perhaps this can be the result of complex noise-induced interactions
      between different central auditory structures. It was, therefore, the aim of the
      present study to investigate the effects of noise exposure on the spontaneous
      electrical activity of single neurons in a slice preparation of the isolated
      mouse IC. Normal hearing mice were exposed to noise (10 kHz center frequency at
      115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun 10:1).
      After one week, auditory brainstem response (ABR) recordings and extracellular
      single-unit recordings from spontaneously active neurons within the IC slice were
      performed in noise-exposed and in normal hearing control mice. Noise-exposed
      animals showed a significant ABR threshold shift in the whole tested frequency
      range and a significant lower neuronal spontaneous activity in all investigated
      isofrequency laminae compared to controls. In both groups, the firing rate of 80%
      of IC neurons (approximately) increased significantly during the application of
      the GABA(A) receptor antagonist Bicucullin (10 microM). The present findings
      demonstrate a noise-related modulation of spontaneous activity in the IC, which
      possibly contribute to the generation of noise-induced tinnitus and hearing loss.

PMID- 15714696
TI  - 2004 ASHG Award for Excellence in Human Genetics Education. Introductory speech
      for Robert J. Gorlin.

PMID- 15714697
TI  - 2004 Curt Stern Award Address. Introductory speech for Neil Risch.

PMID- 15714698
TI  - Angioplasty and stenting of the cervical carotid artery with distal embolic
      protection of the cerebral circulation.

PMID- 15714699
TI  - Extracorporeal shock wave treatment for chronic tendinitis of the elbow (lateral
      epicondylitis).

PMID- 15714700
TI  - Special report: intra-articular hyaluronan for osteoarthritis of the knee.

PMID- 15714701
TI  - Choice: ethical and legal rehabilitation challenges.
AB  - The concept of choice, which has been inherent in the rehabilitation process
      since its inception, has evolved into legal mandates and ethical challenges for
      rehabilitation professionals during the latter part of the 20th century. This
      article identifies the ethical and legal issues related to choice, summarizes a
      pilot project on rehabilitation counselors' perceptions of choice, and provides
      recommendations for rehabilitation professionals in the resolving ethical
      dilemmas related to choice.

PMID- 15714702
TI  - Ethical issues in addiction counseling.
AB  - Although all counselors face ethical challenges, addictions counselors encounter
      ethical issues that are, in many respects, unique to their discipline. This
      article provides an overview of these issues, which include but are not limited
      to (a) the lack of communication and continuity between research and clinical
      practice, (b) lack of agreement over the necessary professional credentials, (c)
      the questionable propensity of group work in the addictions field, (d) special
      issues of confidentiality and privileged communication, (e) boundaries of
      professional practice in making treatment decisions, and (f) unusual
      circumstances of informed consent. In addressing these issues, addictions
      counselors must not only uphold the ethical standards of their profession, they
      must also be cognizant of any federal statutes that may supersede their state
      regulations and act in accordance with them.

PMID- 15714703
TI  - Ethical issues in expert opinions and testimony.
AB  - As the private sector rehabilitation industry matures, certain ethical and
      malpractice issues have emerged. This article provides an overview of ethical
      issues in private for-profit practice, with particular focus on expert testimony,
      using examples from a sample of claims filed with the National Association of
      Rehabilitation Professionals in the Private Sector (NARPS), malpractice insurance
      companies, selected court cases, and complaints submitted to NARPPS Standards
      Compliance Review Board Committee and the Commission on Rehabilitation Counselor
      Certification. It is evident that complaints have a direct relationship to at
      least half of the ethical canons of the Code of Professional Ethics for
      Rehabilitation Counselors because they most frequently involve issues related to
      competence, the client-counselor relationship, professional relationships,
      confidentiality, and use of the certified rehabilitation counselor (CRC)
      designation.

PMID- 15714704
TI  - [Charcot, Freud and the unconscious].
AB  - The aim of this work is to assess, on an historical and critical point of view,
      the new psychological perspective, introduced by Charcot (1825-1893), during the
      ten last years (1882-1892) of his life to explain hysteria symptomas. From
      clinical examples (hypnosis and hypnotherapy, "hystero-traumatism",
      "psychological theory of hysteria", "faith healing"), the paper shows how
      psychological dimension went back into the Parisian Hospital Medicine. This
      occurred on the late XIXth century, just one century after Mesmer, when Freud was
      Charcot's intern, at La Salpetriere hospital, during years 1885-1886. The return
      of a non-rational thought into hospital medicine upset the organicist concepts of
      the Parisian "Ecole anatomo-clinique".

PMID- 15714705
TI  - [History of the rhenish and alsacian contributions to the understanding of
      diabetes].
AB  - The history of diabetes mellitus is punctuated from the Egyptian Antiquity by
      sometimes amazingly acute clinical observations and inversely several missed
      opportunities on the way of the discovery of the mechanisms of the disease and of
      the development of its therapies.Alsace, and more generally the Rhine countries,
      have played a major role in this adventure, of which a crucial step has been the
      experimental demonstration of the role of the pancrease in the pathogenis of the
      disease by Oskar Minkowski and Joseph von Mering in Strasbourg in 1889.

PMID- 15714706
TI  - [Edouard Laguesse at Lille in 1893 created the term "endocrine" and opened the
      endocrinology era].
AB  - In 1893 Edouard Laguesse decided to name the peculiar tiny heaps of cells of
      pancreas after Langerhans who had discovered them in 1869. As he thought the
      secretion of these cell heaps was regulating glycaemia he provoked doubt in the
      minds of his contemporaries but in the same time he was on the way to discovery
      of a new hormone which was to be at the birth of "endocrinology".

PMID- 15714708
TI  - New dawn for Africa.

PMID- 15714709
TI  - Hope after miscarriage.

PMID- 15714710
TI  - Heart of the matter.

PMID- 15714711
TI  - Extreme fear.

PMID- 15714712
TI  - Operation clean-up.

PMID- 15714713
TI  - The perfect patient.

PMID- 15714714
TI  - Hidden tension.

PMID- 15714715
TI  - In case of an emergency.

PMID- 15714716
TI  - A procedure for the digital removal of faeces.
AB  - This article describes the development of an evidence-based procedure for the
      digital removal of faeces (DRF) and the problems and barriers encountered--not
      least the absence of primary evidence. The procedure for DRF that evolved is
      based on the best evidence available. It sets out the criteria for performing DRF
      and directs the practitioner's actions, while still being adaptable to the
      individual patient's situation. It should help to ensure that nurses performing
      DRF do so within the remit of their professional and legal responsibilities, and
      that patients receive the most effective care grounded in the current state of
      knowledge.

PMID- 15714717
TI  - Ongoing consent to care for older people in care homes.
AB  - Obtaining informed consent is a fundamental part of the care-giving process.
      Current policy documents emphasise the importance of including patients in
      planning their care. This article explores the concept of consent and the
      challenges to this concept for older people in long-term care, where consent is
      not a one-off event requiring a 'consent form', but just one stage in the
      continuum of involvement for service users. At one end of the spectrum, service
      users may be unaware that they have a service user plan (care plan), while at the
      other end they may be enabled to complete an advance statement of their wishes,
      thus demonstrating significant involvement in planning their care.

PMID- 15714718
TI  - Hypothermia: assessment, treatment and prevention.
AB  - Hypothermia is a condition that can have serious consequences, yet its symptoms
      are often unrecognised in older people because they can be easily confused with
      symptoms of other age-related illnesses. Nurses should know how to treat the
      condition, as well as be able to offer health promotion and health education
      advice about keeping warm.

PMID- 15714719
TI  - Influenza vaccination of healthcare workers: institutional strategies for
      improving rates.
AB  - The nosocomial transmission of influenza has been well documented since the 1970s
      with both direct and indirect effects of outbreaks in healthcare settings.
      Outbreaks can directly increase morbidity among patients and residents of long
      term care facilities. Indirect effects include disruption of normal operations of
      healthcare institutions, shortages of healthcare workers (HCWs), fewer elective
      admissions, and income loss due to absenteeism. Influenza vaccination of United
      States HCWs remains below 40% despite the availability of a safe, effective
      vaccine and a long-standing recommendation for vaccination of HCWs. New
      strategies to improve the rate of influenza vaccination among HCWs are needed as
      the percentage of those receiving yearly vaccination has changed little in the
      past 20 years. Increasing HCW influenza vaccination coverage calls for a paradigm
      shift, institutions should view vaccination of HCWs as a crucial part of a
      comprehensive infection control program designed to protect patients and staff.
      Administrators of hospitals, long-term care facilities, and other health agencies
      should respond to this challenge by developing programs to improve yearly
      influenza vaccination of their staff Such efforts would put these employees into
      compliance with national recommendations and also benefit the institution by
      reducing absenteeism, nosocomial influenza transmission, and the associated
      economic losses and disruption of routine operations.

PMID- 15714720
TI  - Racial disparities in health between white and African American family practice
      patients: clinical implications.
AB  - OBJECTIVE: To identify differences in self-reported health status and prevalence
      of chronic disease between African American and white patients. STUDY DESIGN: A
      representative sample of African American and white adult patients from a
      stratified sample of family practices in North Carolina completed a questionnaire
      that included self-reported racial status, certain sociodemographic data, health
      risk factors, chronic conditions, and health status measures. DATA SOURCE: The
      North Carolina Health Project, a practice-based cohort of adult patients from a
      representative sample of family practice offices in North Carolina. PRINCIPAL
      FINDINGS: African Americans report poorer general health status than whites.
      Obesity insufficient exercise, high blood pressure, and diabetes are more
      prevalent among African American than white family practice patients, even after
      adjusting for age, gender, and educational attainment. CONCLUSIONS: This study
      complements previous evidence of disparities in chronic disease and health risk
      factors between African Americans and whites, and it highlights specific factors
      that may be important in the primary care setting. RELEVANCE: By focusing
      clinical attention on the prevention or treatment of specific factors that are
      known to be more prevalent among certain racial groups, primary care providers
      may help to reduce racial differences in healthcare.

PMID- 15714721
TI  - Diabetes awareness among African Americans in rural North Carolina.
AB  - OBJECTIVE: To evaluate the extent of diabetes unawareness in rural North
      Carolina. METHODS: Randomly administered an eight-question survey to African
      Americans age 15-74 living in Halifax County North Carolina. RESULTS: Ninety-five
      out of 116 eligible participants completed the survey (82% response rate). Most
      (67%) of the participants reported having two or more major risk factors for Type
      II diabetes (diabetes mellitus). More than half (51.6%) of the participants were
      obese. Most (96.8%) of the participants reported having been tested for diabetes
      at some point in their lives (10% testedpositive, only 8.4% of the remaining 9o%
      reported ever having a second test). CONCLUSION: Diabetes mellitus is a very
      prevalentproblem among the African American population of Halifax County North
      Carolina. Our study underscores the fact that patients are not systematically
      screened and followed-up for diabetes melitus. More healthcare and commnity
      programs need to be adapted to fight this serious public health problem.

PMID- 15714722
TI  - The challenges of eliminating racial and ethnic health disparities: inescapable
      realities? Perplexing science? Ineffective policy?
AB  - Despite the accomplishments of American medical science and the impressive array
      of healthcare facilities and service delivery models available in this country,
      the existence of significant health disparities is a matter of urgent national
      and state health policy priority. Policies to address these issues should address
      fundamental problems having to do with access to care (such as health insurance
      coverage and the availability and the geographic and culturally-appropriate
      accessibility of personal health services), the educational preparation of
      healthcare professionals for the challenge of caring for the increasing diversity
      of patients in a truly "patient-centered" healthcare system of the future,
      efforts to deal with widespread problems of health literacy that reduce the
      likely impact and effectiveness of healthcare, and a more aggressive effort to
      assure that future medial science continues to include minorities and women (and
      they continue to participate) as subjects in clinical trials of innovative
      therapeutic interventions. The policy agenda to address these issues is both
      broad and demanding, as would be expected of any set of problems which is so
      widespread and complex. But, America is no stranger to challenges, and few are
      more worthy of the effort than this.

PMID- 15714723
TI  - Perceptions of racial and ethnic differences in access to healthcare.

PMID- 15714724
TI  - Health issues facing the state's American Indian populations.

PMID- 15714725
TI  - Health disparities among North Carolina's Latinos: our point of view.

PMID- 15714726
TI  - North Carolina's response to the challenge of health disparities.

PMID- 15714727
TI  - Community health centers and their role in reducing healthcare disparities in
      North Carolina.

PMID- 15714728
TI  - Churches, academic institutions, and public health: partnerships to eliminate
      health disparities.
AB  - The four principles represent a framework for improving the process of
      establishing sustainable partnerships between research, public health, and faith
      based institutions that seek to eliminate health disparities. To improve the
      efficacy of partnerships with churches identification of potential partner
      churches must be deliberate, trusting relationships must be built, divergent
      perspectives must be communicated and reconciled, and some tangible power should
      be transferred to church and community leaders where feasible. We applaud the
      National Institutes of Health, through the National Center on Minority Health and
      Health Disparities', efforts to "promote coordination and collaboration among the
      agencies conducting or supporting minority health or other health disparities
      research." We recommend that the North Carolina Office of Minority Health and
      Health Disparities be charged with and provided adequate resources to facilitate
      this type of coordination and collaboration among North Carolina Department of
      Health and Human Services agencies that are disparities conducting or supporting
      minority health and health research. A special emphasis should be placed on
      partnerships that seek to engage communities of faith.

PMID- 15714729
TI  - Health disparities, the faith agenda, and health promotion/disease prevention:
      the General Baptist State Convention of North Carolina model.

PMID- 15714730
TI  - Northeastern North Carolina Partnership for Public Health and Health Disparities
      in Northeastern North Carolina.

PMID- 15714731
TI  - Numbers of minority health professionals: where do we stand?
AB  - This overview has pointed to a continuing racial and ethnic imbalance in the
      health professions that applies to North Carolina as well as the nation. Great
      strides have been made early in the development of programs to enhance racial and
      ethnic representation, but they have generally reached a plateau in terms of
      growth and progress. Resistance to affirmative action programs and subsequent
      uncertainty over their legal standing can be cited as one factor thwarting
      progress, but that issue has been resolved and schools, professions, and the
      North Carolina General Assembly can move forward with a clear understanding of
      how to proceed. A full generation has matured with the benefit of positive
      emphasis on increasing the proportion of minorities in the health professions.
      The coming generations must build and expand on the programs and initiatives that
      brought the nation and the state to where we are now. But these goals must be re
      stated, and intensified efforts are required if any reasonable parity in
      representation of minorities among the health professions is to be achieved.

PMID- 15714732
TI  - Minority recruitment and participation in health research.

PMID- 15714733
TI  - The health of American Indians in North Carolina.

PMID- 15714734
TI  - Quality care and performance improvement.

PMID- 15714735
TI  - Quality care and performance improvement.

PMID- 15714736
TI  - The leadership role of medical-surgical nurses: what is it?

PMID- 15714737
TI  - Advocacy through patient teaching.

PMID- 15714738
TI  - Assessment of pain in elders with dementia.
AB  - The importance of pain assessment and the available measurement tools for elders
      with dementia are reviewed. The authors recommend measuring chronic pain during
      active movement, and looking at inactivity, changes of motor patterns, and
      disruptive behaviors as indicators of pain. They also suggest querying elders
      about their pain even if they suffer from dementia.

PMID- 15714739
TI  - Apoptosis: understanding the new molecular pathway.
AB  - Advances in science have increased the knowledge of how cells die in the body
      (apoptosis). A basic understanding of this process can improve nurses' ability to
      review new scientific literature and enable them to provide safer bedside care.

PMID- 15714740
TI  - Nurse's guide to understanding and treating thrombotic occlusion of central
      venous access devices.
AB  - Over 5 million central venous access devices (CVADs) are placed in the United
      States annually. Catheter occlusion is the most common non-infectious
      complication in long-term use of CVADs. Nursing management of the thrombotic
      occlusion of central venous access devices is described. The normal process of
      hemostasis and fibrinolysis and common types of catheter thrombosis are reviewed,
      along with the step-by-step procedure for restoring catheter patency using
      thrombolytic agents.

PMID- 15714741
TI  - Complementary and alternative medicine: a qualitative study of beliefs of a small
      sample of Rocky Mountain area nurses.
AB  - In this study, a descriptive, qualitative approach was used to investigate
      attitudes of a sample of Rocky Mountain area nurses regarding complementary and
      alternative medicine (CAM). The major theme was a lack of congruence between
      acute care nurses' personal experiences with CAM and incorporation of CAM into
      their practice.

PMID- 15714742
TI  - Evaluation and revision of a clinical advancement program.
AB  - Career advancement programs have been used for decades to provide promotion
      opportunities for bedside nurses. Few of the programs have been evaluated to
      determine their efficacy and the overall satisfaction to registered nurses. An
      evaluation of a career advancement system in a community hospital setting was
      conducted to identify the perceived lack of interest in pursuing promotion with
      the current process.

PMID- 15714743
TI  - Pain: geriatric self-learning module.
AB  - The Geriatric Resource Nurse Model is used at the University of Virginia to
      improve the competency of staff in caring for older adults. Eight self-learning
      educational modules were developed to address common concerns in hospitalized
      elders. The Pain: Geriatric Self-Learning Module to published here, along with a
      post-test. This is the second in a four-part publication of self-learning
      modules.

PMID- 15714744
TI  - Problems with eating and nutrition: geriatric self-learning module.
AB  - The Geriatric Resource Nurse Model is used at the University of Virginia to
      improve the competency of staff in caring for older adults. Eight self-learning
      educational modules were developed to address common concerns in
      hospitalizedelders. The Problems With Eating and Nutrition: Geriatric Self
      Learning Module is published here, along with a post test. This is the second in
      a four-part publication of self-learning modules.

PMID- 15714745
TI  - Legionnaire's disease: a current update.
AB  - Legionnaire's disease was first identified and described in January 1977. Even
      today, it is often regarded as an unusual or exotic disease, when in fact it is a
      very common form of community and nosocomial acquired pneumonia. The major roles
      of the acute care nurse, including patient health education; psychosocial needs
      of the patient; and strategies for disease prevention and control, are discussed.

PMID- 15714746
TI  - The clinical utility of genetic information in the care of persons with
      Alzheimer's disease.
AB  - Genetic research about Alzheimer's disease (AD) is advancing quickly, but the
      clinical utility of these gene discoveries remains unclear. The clinical context
      of genetic research in AD is discussed.

PMID- 15714747
TI  - The 'alphabet' of rheumatoid arthritis treatment.

PMID- 15714748
TI  - Ethical decision making and nursing.

PMID- 15714750
TI  - Estimation of EDRF and nitric oxide release using [3H]GTP-labeled human
      platelets.
AB  - We have developed a new bioassay for endothelium-derived relaxing factor (EDRF)
      or nitric oxide (NO) using human [3H]guanosine triphosphate (GTP)-labeled
      platelets. The labeled platelets were preincubated with isobutyl-methylxanthine
      and co-cultured with endothelial cells and the [3H]cyclic guanosine monophosphate
      (cGMP) formed was isolated by ion-exchange chromatography. Endothelial cells,
      either in monolayer cells or in suspension, increased platelet cGMP accumulation
      dose-dependently, a significant increase being detected with 5000 endothelial
      cells or more/assay when suspended cells were used. Co-culturing with the same
      number of skin fibroblasts failed to elevate platelet cGMP. Preincubation of
      endothelial cells with bradykinin and superoxide dismutase (SOD) synergistically
      potentiated the increase in platelet cGMP, but was attenuated by Nomega-nitro-L
      arginine, with partial restoration by L-arginine but not by D-arginine. These
      compounds, however, did not affect cGMP accumulation by sodium nitroprusside.
      Moreover, preincubation of the labeled platelets with the NO synthase inhibitor
      prior to EDRF assay had no effect. We conclude that [3H]GTP-labeled platelets
      could provide a simple, sensitive and specific bioassay for estimating EDRF or NO
      release.

PMID- 15714749
TI  - The treatment of severe or recurrent deep venous thrombosis. Beneficial effect of
      the co-administration of antiplatelet agents with or without rheological effects,
      and anticoagulants.
AB  - Deep venous thromboses can be divided into two groups according to their
      pathogenesis, anatomical features and differing responses to therapy. The first
      and most frequent consists of so-called simple venous thrombosis while the second
      group, which is less common, comprises severe or recurrent venous thrombosis
      characterised by a multifactorial pathogenesis, a mixed thrombus rich in
      platelets and by an incomplete response to both prophylactic and therapeutic
      treatment with anticoagulants (heparin or vitamin K antagonist). In a randomized,
      prospective blind study in patients with severe or recurrent venous thrombosis,
      which included 6 groups each of 100 patients, co-administration of anticoagulants
      with various types of antiplatelet agent, either with rheological effects
      (piracetam, buflomedil, pentoxifylline) or without them (dipyridamole), has shown
      a beneficial potentiating antithrombotic effect with those drugs possessing
      rheological effects and the absence of this effect with dipyridamole.

PMID- 15714751
TI  - The influence of age and smoking on hemostatic parameters in the chinese people.
AB  - Plasma plasminogen activator inhibitor-1 (PAI) antigen, fibrinogen, factor VII,
      cholesterol, triglyceride (TG) and glucose were determined in 101 healthy
      subjects, who were divided into 10 subgroups according to age and smoking status.
      Factor VII and cholesterol were significantly higher in 50 healthy smokers than
      in the remaining 51 healthy non-smokers (p = 0.037 and 0.008, respectively). By
      dividing smokers and non-smokers each into 5 different age groups, we found that
      smoking could significantly increase PAI and/or factor VII, but not fibrinogen,
      in several age groups. On the other hand, age would significantly increase
      fibrinogen in either smokers or non-smokers, and this increase would be promoted
      by smoking. In conclusion, smoking could produce higher factor VII or PAI,
      whereas age could effect the significant increase of fibrinogen which was further
      promoted by smoking. Though aging cannot be avoided, smoking should be abstained
      especially in the old people to prevent the occurrence of thromboembolic
      diseases.

PMID- 15714752
TI  - Species differences in platelet responses to thrombin and SFLLRN. receptor
      mediated calcium mobilization and aggregation, and regulation by protein kinases.
AB  - The thrombin receptor on human platelets is activated by thrombin to stimulate
      platelet aggregation through the tethered ligand SFLLRN. This study examined the
      effects of thrombin and SFLLRN on aggregation and calcium mobilization ([Ca2+]i)
      in rat, guinea pig, rabbit, dog, monkey, and human platelets, and the role of
      protein kinases in regulating these functions. Thrombin induced platelet
      aggregation and [Ca2+]i in all species studied; however, only guinea pig, monkey
      and human platelets were responsive to SFLLRN. Similar species specific effects
      were obtained with [Ca2+]i studies. The kinetic profile for [Ca2+]i differed
      among species, suggesting that regulatory mechanisms for calcium differed between
      agonists and among species. Staurosporine, a non-selective inhibitor of protein
      kinases, inhibited platelet aggregation induced by thrombin or SFLLRN in all
      species. Staurosporine inhibited thrombin-induced [Ca2+]i in guinea pigs, had no
      effect in rat, and increased [Ca2+]i in all other species. Staurosporine
      inhibited SFLLRN-induced [Ca2+]i in guinea pig, yet had no effect in monkey or
      human. Tyrphostin 23, a specific inhibitor of tyrosine protein kinases, inhibited
      thrombin-induced aggregation of rabbit, monkey, dog and human platelets. SFLLRN
      induced aggregation was also inhibited by tyrphostin 23. Tyrphostin 23 inhibited
      [Ca2+]i induced by either thrombin or SFLLRN in all species. Based on the
      differential response to agonist stimulation, we propose that thrombin can
      activate platelets via SFLLRN-dependent and independent mechanisms, which could
      involve yet unrecognized subtypes of the thrombin receptor or distinct cellular
      activating mechanisms. Furthermore, differential regulation of calcium
      mobilization and aggregation was observed in those platelets responding to either
      thrombin or SFLLRN.

PMID- 15714753
TI  - The effect of sex and age on antithrombin biosynthesis in the rat.
AB  - Antithrombin is the primary inhibitor of Factor Xa and thrombin. Numerous reports
      have indicated that age and sex can influence antithrombin levels, but details of
      the regulation of antithrombin biosynthesis are not known. Thus, a
      characterization of antithrombin mRNA in eight tissues of young and old male and
      female rats was carried out. Liver produced the most mRNA, and hence contributes
      the majority of the plasma antithrombin, followed by the kidneys, with no age or
      sex related differences in mRNA levels being observed. Elevated amounts of mRNA
      were detected in aortas of old male rats compared to young ones. No antithrombin
      mRNA was detected in brain, lung, heart or skeletal muscle, and spleen showed low
      but variable levels. Plasma antithrombin protein was elevated in old female rats
      compared to young female or old male rats. These results show that the rat
      provides a potentially useful system to study the in vivo regulation of
      antithrombin biosynthesis.

PMID- 15714754
TI  - The dimeric Aalpha chain composition of dysfibrinogenemic molecules with
      mutations at Aalpha 16.
AB  - In the last stage of fibrinogen synthesis, two Aalpha-Bbeta-gamma half-molecules
      are disulfide linked in their N-terminal regions to form a dimeric fibrinogen
      molecule. It is not known whether intracellular hepatocyte assembly of fibrinogen
      half-molecules occurs randomly or is a directed process. One analysis based on
      partitioning of coagulable components of fibrinogen from a heterozygous
      dysfibrinogenemic subject having a mutation at the thrombin cleavage site
      (Fibrinogen Louisville, Aalpha16 R-->H), suggested that only homodimeric
      molecules containing two normal fibrinopeptides A (FPA, FPA) or two abnormal
      fibrinopeptides A (FPA*, FPA*) were present in plasma, implying that fibrinogen
      dimer assembly is directed. The same type of analyses on Fibrinogen Birmingham
      (Aalpha16 R-->H) indicated that there were heterodimers as well as homodimers,
      suggesting that fibrinogen dimer assembly is random. To examine this question
      more directly, the composition of fibrinogen molecules from seven
      dysfibrinogenemic families with either R-->C (four) or R-->H (three) Aalpha16
      mutations was determined. Following treatment with Atroxin to release normal FPA
      from fibrinogen, N-terminal disulfide knot ('N-DSK') cleavage fragments were
      prepared and subsequently separated by SDS-PAGE to resolve 'N-DSK' components
      with two FPA*'s (N-DSK homodimer), one FPA* (des A N-DSK heterodimer), or no
      FPA's (des AA N-DSK homodimer). Fibrinogen from subjects whose molecules
      contained both normal and abnormal Aalpha chains, yielded a heterodimeric des A N
      DSK derivative, as well as smaller amounts of homodimeric N-DSK and des AA N-DSK.
      These results indicate that when both types of Aalpha chain are produced, both
      Aalpha chain alleles are expressed and the resulting fibrinogen dimers are
      assembled randomly.

PMID- 15714755
TI  - Effect of ketanserin on platelet function and bleeding time in uremic patients
      treated with erythropoietin.

PMID- 15714756
TI  - Gly-pro-arg-pro (GPRP) enhances free thrombin.

PMID- 15714757
TI  - Mechanism of fatty acid synthesis.

PMID- 15714758
TI  - Immunoreproduction.

PMID- 15714760
TI  - Synergistic uterotrophic effect of gibberellic acid and estradiol in the immature
      mouse.

PMID- 15714759
TI  - A peptide-like inhibitor of N-methyltransferase in rabbit brain.

PMID- 15714761
TI  - Effects of ergots on adenylate cyclase activity in the corpus striatum and
      pituitary.

PMID- 15714762
TI  - Cyclic succinic dehydrogenase activity in rat liver mitochondria.

PMID- 15714763
TI  - The adrenal and vascular effects of angiotensin II and III in sodium depleted
      rats.

PMID- 15714764
TI  - Blockade of the picrotoxin-induced in vivo release of dopamine in the cat caudate
      nucleus by diazepam.

PMID- 15714765
TI  - Hyperglycemia in mice of the Goodale Giant (G/Gw) strain.

PMID- 15714766
TI  - Cerebroventricular administration of somatostatin (SRIF): effect on central
      levels of cyclic AMP.

PMID- 15714767
TI  - Analgesic activity of enkephalins following intracerebral administration in the
      rat.

PMID- 15714768
TI  - The action of black widow spider venom on cholinergic mechanisms in synaptosomal
      preparations of rat brain cortices.

PMID- 15714769
TI  - Enhanced platelet aggregability in dogs following myocardial infarction.

PMID- 15714770
TI  - Interaction of progesterone with amphibian melanosomes.

PMID- 15714771
TI  - Rat brain aryl acylamidase: multiple forms and inhibition effects of LSD,
      serotonin and related compounds.

PMID- 15714772
TI  - Creatine kinase isoenzyme associated with synaptosomal membrane and synaptic
      vesicles.

PMID- 15714773
TI  - An animal model for the measurement of acute tolerance to ethanol.

PMID- 15714774
TI  - Tolerance to hypokinesia elicited by dopamine agonists in mice: hyposensitization
      of autoreceptors?

PMID- 15714775
TI  - Effect of cold pressor stimulation on plasma norepinephrine, dopamine-beta
      hydroxylase, and renin activity.

PMID- 15714776
TI  - Electron paramagnetic resonance studies on hepatic microsomal cytochrome P-450
      from a marine teleost fish.

PMID- 15714778
TI  - Another DON bites the dust!

PMID- 15714779
TI  - Support surfaces. A strategic approach to investing in prevention and treatment
      support surfaces.

PMID- 15714780
TI  - Evaluating your resident monitoring needs.

PMID- 15714781
TI  - A liberalized approach to diets for diabetes in long term care.
AB  - These guidelines allow for liberalization of the dietary treatment of diabetes in
      type 2 diabetics in long term care facilities. The care team should work together
      to promote specific policies and protocols in the facility to address how
      individual type 2 diabetics will be assessed, and which diets will be offered as
      an adjunct to treatment. Careful monitoring of blood glucose levels, medications
      and response to treatment may allow for more liberalization of the diet. Diet
      liberalization can help to promote better health and improved quality of life for
      our elderly residents.

PMID- 15714782
TI  - Integrative care--headaches.

PMID- 15714784
TI  - Emerging ethical issues in nephrology nursing--part I.

PMID- 15714785
TI  - Tissue plasminogen activator (t-PA) efficacy in the restoration of hemodialysis
      catheter function.
AB  - Thrombus formation within hemodialysis catheters contributes to inadequate
      dialysis and adverse patient outcomes. A thrombolytic agent may be required to
      restore patency and improve blood flow. This study evaluates the efficacy of
      instilling low dose (1 mg/ml) t-PA in catheter lumens to restore patency in
      malfunctioning catheters. t-PA was utilized to treat suspected catheter thrombus
      over a four-month period. Seventeen patients with 21 catheters (12 temporary, 9
      permanent) received 40 doses of t-PA. Catheter function was restored in 39 of 40
      cases (97.5%). Significant improvement in blood flow was confirmed by paired t
      test (p < 0.001). Sustained improvement in blood flow was confirmed by ANOVA (p <
      0.001). The mean primary patency of all catheters was 29.7 days (SD = 27.0 days).
      No adverse patient effects were noted. These results demonstrate that t-PA can
      safely and effectively restore blood flow and extend patency in hemodialysis
      catheters.

PMID- 15714786
TI  - On-line optical sensing of blood volume changes to prevent intradialytic
      hypovolemia.
AB  - Intradialytic hypovolemia is a common complication of hemodialysis treatments.
      Blood volume changes that occur during dialysis can be followed by on-line
      optical sensing of the patient's hematocrit. Characteristic curves of blood
      volume changes can be seen in fluid overloaded patients with symptoms of
      hypovolemia, i.e. cramps, hypotension. The relative blood volume changes in those
      who have fluid removed to their ideal "dry" weight without symptoms will be shown
      in comparison. As Phase I of a CQI project, the nephrologist and dialysis nurses
      at the London Health Sciences Centre performed a cross-sectional study to define
      the frequency of these curves and their relationship to intradialytic symptoms.
      The analysis of these curves can be used to re-assess "dry" weights, prevent
      intradialytic hypovolemia and decrease the use of antihypertensive agents. The
      correlation of our findings with the results of an independent hypotensive CQI
      study will be presented.

PMID- 15714787
TI  - The lived experience of adolescents who transfer from a pediatric to an adult
      hemodialysis centre.
AB  - The transition experience of adolescent patients who transfer from pediatric to
      adult hemodialysis centres has not received attention in the pediatric nephrology
      literature. In order for health care professionals from both pediatric and adult
      hemodialysis centres to positively influence the quality of life during this
      transition, an understanding of the meanings adolescents attach to their
      transition experience must be explored. Phenomenology as a research paradigm was
      employed for this study. Phenomenology provides a method from which to study
      human experience as it is lived, including the meanings that individuals attach
      to the experience. This qualitative research study was designed to describe the
      meanings adolescents attached to their transition experience. Subsequent
      objectives of the study were: to identify implications for professional practice
      in both pediatric and adult hemodialysis centres; to positively influence the
      quality of life for adolescent hemodialysis patients during their transition; and
      to identify and define potential areas for further research related to the
      holistic needs of adolescent hemodialysis patients. A sample of three English
      speaking adults between the ages of 18 and 22 years who were receiving
      hemodialysis treatments in an adult centre following transfer from a pediatric
      centre within one year were interviewed. The tape-recorded interviews were
      transcribed into verbatim text. In addition, field notes provided investigators
      with the supplemental information about the meaning and the context of the
      interview that the audiotape may have missed. The data were analyzed using a step
      by-step procedure adapted from Colaizzi (1978). In the final step, the
      investigators integrated and synthesized the analysis into a descriptive meaning
      of the transition experience of adolescents who transferred from a pediatric to
      an adult hemodialysis centre. The findings of the study revealed a major theme of
      ownership that the adolescents described as being achieved in the adult
      hemodialysis centre through their increased knowledge of dialysis technology,
      through being held accountable for their dialysis care and through increased
      feelings of independence.

PMID- 15714788
TI  - Yes, miracles do happen: a story of an infant on peritoneal dialysis.
AB  - The purpose of my writing this story is to share an experience I had as a
      nephrology nurse at the London Health Sciences Centre. I'm sure as nurses we have
      all been involved with patients whom you know you will never forget and who have
      influenced your life as a caregiver. Such is the case with Baby M. This is a
      story of an infant on peritoneal dialysis.

PMID- 15714789
TI  - [Methods and modes about the theory of traditional Chinese prescription
      composition].
AB  - Theory and mode about compatibility of prescription are the key element for
      studies on complex prescription in traditional Chinese medicine. In this article,
      we reviewed the sources, methods and thoughtway about theory of prescription
      composition, and concluded the current researches about components compatibility.
      Through introducing the researches about compatibility of effective components,
      we advanced that components compatibility would be one of the new modes of
      compound prescription of Chinese medicine. The researches and foundation about
      the new modes of compound prescription of Chinese medicine would do active
      influence either in making modern Chinese medicine or in increasing clinical
      curative effect.

PMID- 15714790
TI  - [A preliminary investigation on safety evaluation system for health foods].
AB  - OBJECTIVE: In order to guarantee the safety of health foods, a safety evaluation
      system has been initially proposed. METHOD: Based on both experienced and
      experimental safe data of health foods, different safety criteria could be
      divided. RESULT: A safety evaluation system with five criteria has been finally
      established, ingredients listed in the first three safe criteria were suitable
      for health foods. CONCLUSION: This system could be applied for the selection of
      relevant ingredients of health foods at R&D stage, and it would be improved after
      certain period of implementation.

PMID- 15714791
TI  - [A study on the rotation of crops among Panax quinquefolium, Perilla frutescens
      and Coix lacryma-jobi].
AB  - OBJECTIVE: To provide evidence for establishing an efficient method of growing
      Panax quinquefolium by rotation of crops. METHOD: Four-year old P. quinquefolium
      was cultivated in water and soil cultures. Biological assays were conducted with
      the aqueous extracts of P. quinquefolius, Fructus Perillae and roots of Coix
      lacryma-jobi. P. quinquefolium was cultivated in the soil where purple Perilla
      frutesens and C. lacryma-jobi were grown previously. The effects of rotation were
      determined. RESULT: The stems, leaves and fibrous roots of Panax quinquefolium
      contained allelopathic substances. When the concentration of the allelopathic
      substances exceeded 1g per kg soil, P. quinquefolius could not grow. On the other
      hand, when the concentration of allelopathic substances fell below 0.2 g per kg
      soil, the rate of seedling growth was decreased by 25%. When P. quinquefolius was
      cultivated in the soil in which purple Perilla frutesens had previously grown, or
      in the soil supplemented with Fructus Perillae, the rates of seedling growth and
      the yield were raised by 26.8% and 11.5% tively, in comparison with the controls.
      CONCLUSION: Rotation of Panax quinquefolium and Perilla frutesens was shown to be
      a good way for the cultivation of the former. During the growing process,
      application of Fructus Perillae to the soil could further enhance the growth and
      of Panax quinquefolium.

PMID- 15714792
TI  - [Dual-index sequence analytical method for IR fingerprint spectra of the
      chloroform extract of Radix Glycyrrhizae].
AB  - OBJECTIVE: To investigate a new method for the analysis of IR fingerprint spectra
      of Radix Glycyrrhizae. METHOD: Two indexes, common peak ratio and variation peak
      ratio, are used to compare the IR spectra of various Radix Glycyrrhizae samples,
      and the values are calculated by means of sequent analysis. RESULT AND
      CONCLUSION: The dual-index sequence method provides a good approach to
      discriminate Radix Glycyrrhizae samples of different species and geographical
      origins.

PMID- 15714793
TI  - [The growth of Salvia miltiorrhiza seedling and root system following
      transplantation].
AB  - OBJECTIVE: To study the relationship between plant growth and accumulation of
      active ingredients in Salvia miltiorrhiza. METHOD: Transplants of S. miltiorrhiza
      were sampled at 20 day intervals. At each stage, the growth of seedling and root
      system was recorded and the contents of tanshinone II (A) and salvia acid were
      measured. RESULT AND CONCLUSION: This study showed that the rapid growth stage of
      the root system lags behind that of the seedling system, but the growing period
      of root system lasts longer. The quantitative change of roots reveals a double
      "S" curve; two rapid growth stages emerge during 30 - 70 days and 140 - 200 days
      after the seedlings were transplanted. The content of salvia acid reaches the
      highest level during 140 - 180 days, whereas the content of tanshinone peaks
      during 100 - 120 days.

PMID- 15714794
TI  - [Innovation study on Chinese medicinal materials ultrafine grinding by impacting
      and attriting in jet mill].
AB  - OBJECTIVE: To introduce a method of ultrafine grinding by impacting and attriting
      in jet mill, which can solve effectively about grinding efficiency and
      suitability for variant Chinese medicinal materials. METHOD: Raw materials are
      uniformly distributed to multiple nozzles and accelerating pipes, and high-speed
      impact on a rotary target with surface of various friction veining, so Chinese
      medicinal materials are pulverized through recombination action of impaction and
      attrition, and ultrafine powder are separated by internal classifier. RESULT: The
      grinding experiment go to show that average fineness of several kinds of typical
      Chinese medicinal materials powder are 2.0 - 12.7 microns. CONCLUSION: This
      method has obvious advantage of suitability and efficiency for ultrafine grinding
      Chinese medicinal materials.

PMID- 15714795
TI  - [Optimization of purification conditions for with macroporous adsorption resin
      total saponins from smilax china].
AB  - OBJECTIVE: To develop a with high efficiency and practicality for separating and
      purifying total steroidal saponins lax china. METHOD: Using adsorption capacity
      and desorption rate of total steroidal saponins as the primary screening index,
      surveyed, and the optimized conditions of adsorption and desorption of total
      steroidal saponins were studied. RESULT: The adsorption and desorption rate of
      total steroidal saponins reached 16 mg x mL(-1) and 90% respectively for
      macroporous resin HPD100 chosen. Macroporous resin HPD100 could be well used in
      separating and purifying total steroidal saponins from S. china.

PMID- 15714796
TI  - [Analysis of ant oil extracted with supercritical CO2 fluid from Polyrhachis
      vicina by GC-MS].
AB  - OBJECTIVE: To study the optimum extraction parameters and components on ant oil
      from Polyrhachis vicina. METHOD: The optimum condifious for supercritical CO2
      fluid extraction (SFE-CO2), were investigated with orthogonal design, GC-MS was
      applied for analyzing. The components and their contents in the ant oil were
      analyzed by GC-MS, and the contents of lead, zinc and manganese in the oil were
      determined by ICP-AES. RESULT: The optimum extraction parameters were achieved,
      temperature of 50 degrees C, pressure of 30 MPa and time of 2 hours. The
      extracting yield of the ant volatile oil was 11.4% - 14.3%. 51 Constituents were
      identified including 9-octadecenoic acid, ethyl oleate, cholesterol, n-
      Hexadecanoic acid, etc, and the content of various constituents was determined by
      orea normalization. The oil contained unsaturated fatty acid of 64.6%, lead of
      0.80 microg x g(-1), zinc of 0.54 microg x g(-1) and manganese of 0.15 microg x
      g(-1). CONCLUSION: The method showes advantages including faster and efficient of
      extraction, good quality and no solvent residues in the oil.

PMID- 15714797
TI  - [Determination of phillyrin and forsythoside A in Lianqiao Bingdu Qing capsule by
      RP-HPLC].
AB  - OBJECTIVE: To establish methods for the determination of phillyrin and
      forsythoside A in Lianqiao Bingdu Qing capsule by RP-HPLC. METHOD: The
      determination of phillyrin was carried out on YWG-C18 column (4.6 mm x 250 mm, 10
      microm), using acetonitrile-water (25:75) as mobile phase at a flow rate of 0.8
      mL x min(-1) and detected at the wavelength 277 nm. The determination of
      forsythoside A was carried out with YWG-C18 column(4.6 mm x 250 mm,10 microm),
      using acetonitrile-water-Acetic acid (17:83:0.4) as mobile phase at a flow rate
      of 1.0 mL x min(-1) and detected at the wavelength 280 nm. RESULT: The average
      recovery of phillyrin was 99.6%, RSD = 1.9% (n = 5). The average recovery of
      forsythoside A was 101.3%, RSD = 2.5% ( n = 5). CONCLUSION: The methods were
      simple and accurate and could be used to control the quality of the Lianqiao
      Bingdu Qing capsule.

PMID- 15714798
TI  - [Bromophenols from the brown alga Leathesia nana].
AB  - OBJECTIVE: To investigate the chemical constituents of the brown alga Leathesia
      nana. METHOD: Compounds were isolated by normal phase silica gel, Sephadex LH-20
      chromatography and reverse phase HPLC techniques. Their structures were
      elucidated with spectroscopic methods including IR, MS and NMR. RESULT: Six
      compounds were isolated from ethanolic extract of the brown alga L. nana and
      their structures were identified as 2,2',3,3'-tetrabromo-4,4',5,5'
      tetrahydroxydiphenyl methane, 2,2',3-tribromo-3', 4,4', 5-tetrahydroxy-6'
      ethyloxymethyldiphenyl methane, 2,3-dibromo-4,5-dihydroxybenzyl alcohol, 2,3
      dibromo-4,5-dihydroxybenzyl methyl ether, 3-bromo-4-hydroxybenzoic acid and 2
      bromo-4,5-dihydroxybenzaldehyde. CONCLUSION: All these compounds were obtained
      from this species for the first time.

PMID- 15714799
TI  - [Studies on the chemical constituents in vine stem of Bauhinia championii (I)].
AB  - OBJECTIVE: To study the chemical constituents of Bauhinia championii. METHOD:
      Compounds were isolated from the ethanolic extract of B. championii by silica gel
      column Chromatography, and their structures were elucidated by spectral analyses.
      RESULT: Five compounds were isolated and elucidated as 2,4,6-trimethoxyphenol 1-O
      beta-D-(6'-O-galloyl)-glucopyranoside (1), (+/-)-lyoniresinol (2), daucosterol
      (3), beta-sitosterol (4) and gallic acid (5). CONCLUSION: Compounds 1-4 were
      isolated from B. championii for the first time.

PMID- 15714800
TI  - [Isolation and structure elucidation of glycosides in n-butanol extracts from
      rhizome of Periploca calophylla].
AB  - OBJECTIVE: To study the chemical constituents from n-butanol extracts of
      Periploca calophylla. METHOD: The constituents were isolated and purified by
      chromatographic technology and their structures were elucidated on the basis of
      physicochemical property and spectroscopic methods. RESULT: Eight glycosides were
      isolated and identified as periplocin (I), kaempferol 3-alpha-D-arabinoside (II),
      kaempferol 3-O-beta-D-glucoside (III), 3',4',5,7-tetrahydroxyflavanone-2(S)-3'-O
      beta-D-glucopyranoside (IV), (+)-syringaresinol-4'-O-beta-D-monoglucoside (V), 1
      sinapoylglucoside (VI), erigeside C (VII), 2,6-dimethoxy-4-hydroxyphenol 1-O-beta
      D-glucoside (VIII). CONCLUSION: All the compounds were isolated for the first
      time from this plant.

PMID- 15714801
TI  - [Effects of allitridin on the expression of human cytomegalovirus immediate early
      antigens-IE72 and IE86 in human embryonic lung cells].
AB  - OBJECTIVE: To investigate the effect of allitridin injection on the expression of
      human cytomegalovirus (HCMV) immediate-early antigens (IEAs including IE72 and
      IE86) in human embryonic lung cells. METHOD: HCMV AD 169 Virus strain infected
      cell model (MOI = 2.5 and 0.25, respectively) were established, and then treated
      with ICm5 and MTC doses of allitridin. Western blot was used to analyze the of
      IE72 and IE86 expression after the treatment, ganciclovir(GCV, IC50 and 2.3 x
      IC50) treatment as control. RESULT: No matter what kind of MOI was used, both
      IE86 and IE72 antigens' expression was effectively suppressed by allitridin
      treatment, and the inhibitory rate of IE86 was almost twice of IE72's. Compared
      with GCV, allitridin had stronger inhibitory effect on IE86 expressing, although
      its efficacy on IE72 was weaker than GCV. CONCLUSION: Allitridin could suppress
      the expression of IE72 and IE86, especially for IE86 expressing, maybe it is ore
      of key role in the mechanism of allitridin against HCMV.

PMID- 15714802
TI  - [Investigation on the molecular mechanisms of anti-hepatocarcinoma herbs of
      traditional Chinese medicine by cell cycle microarray].
AB  - OBJECTIVE: To design DNA microarray and investigate the molecular anti-tumor
      mechanism of herbs of traditional Chinese medicine. METHOD: cDNA microarrays
      consisting of 56 probes representing 24 human cell cycle genes were constructed,
      Four anti-hepatocarcinoma herbs including Radix Linderae, Hebra Artemisiae
      Annuae, Radix Amebiae, Radix Astragli, were chosen. Effects of herbs on SMMC-7721
      cell cycle were observed by flow cytometry assay. Effects of herbs on cell cycle
      gene expression in SMMC-7721 cells were analyzed by comparing hybridization of
      Dig-Labeled cDNAs from herb-treated cells and cDNAs from untreated cells. RESULT:
      Expressions of cell cycle geneswere changed in different degrees after herbs
      treated. Some genes were down-regulated and some genes were up-regulated. The
      changes in gene expression agreed with the results of flow cytometry assay.
      CONCLUSION: The results suggest that these herbs may have effects on cell cycle
      and DNA damage checkpoint genes which may be the mechanism of the herbs, and DNA
      microarray can be used to investigate the biological function of extracts of
      traditional Chinese medicine.

PMID- 15714803
TI  - [Pseudolaric acid B induces human melanoma A375-S2 cell apoptosis in vitro].
AB  - OBJECTIVE: To study the mechanisms of pseudolaric acid B-induced apoptosis on
      A375-S2 cells. METHOD: MTT, fluorescence microscope observation, DNA agarose gel
      electrophoresis and Western blot analysis wereused. RESULT: Pseudolaric acid
      Binduces A375-S2 cell apoptosis in a time and dose-dependent manner. Apoptotic
      bodies and DNA ladder were observed in 5 micromol x L(-1) pseudolaric acid B
      treated A375-S2 cells for 36 h. The expression of Bcl-2, Bcl-xL and ICAD was
      reduced time dependently, whereas the expression of Bax was increased.
      CONCLUSION: The major cause of pseudolaric acid B induced cytotoxicity on A375-S2
      cells was apoptosis. Mitochondria proteins and ICAD might be involved in the
      apoptotic pathways of pseudolaric acid B-treated A375-S2 cells.

PMID- 15714804
TI  - [Study of Shugan Yiyang capsule on erectile dysfunction].
AB  - OBJECTIVE: To study the pharmacological effect of Shugan Yiyang(SGYY) capsule.
      METHOD: kongming mice and Wistar rats were used to observe the effects of SGYY
      capsule on sexual desire, erection, ejaculation and fatigue. The weight of
      prostate, seminal vesicle, testes, levators and thymus and serum testosterone
      level were also measured. Furthermore, Rhesus monkey were used to construct
      animal model of erectile dysfunction. Effects of SGYY capsule on sexual behavior,
      penile blood flow and electromyogram were observed. RESULT: SGYY capsule can
      remarkably reduce the incubation period of erection, ejaculation and innovate the
      sexual desire,erection, ejaculation both on rats and rhesus monkeys. The weight
      of prostate, seminal vesicle, testes, levators in mice and serum testosterone
      level of rats increased while the weight of thymus decreased. It can also
      diminish the luminar of vein and reduce the venous outflow while the transmission
      of peripheral nervous system remained stable. CONCLUSION: SGYY capsule can
      remarkably improve the erectile activity, sexual desire and ejaculatory activity.
      The mechanism of SGYY capsule may be related to the increase of androgen and
      adrenocorticohormone levels. as well as the reduction of penile venous outflow.
      [Key words] shuganyiyang capsule; er

PMID- 15714805
TI  - [Study of baicalin in inducing prostate cancer cell line DU145 apoptosis in
      vitro].
AB  - OBJECTIVE: The purpose of the present study was to investigate the in vitro
      effects of baicalin on induction of apoptosis in human prostate cancer cell line
      DU145. METHOD: Human prostate cancer cell line DU145 was treated with different
      concentration of baicalin in vitro. The apoptosis rate was determined by FACS
      analysis, cell cycle distribution was detected by flow cytometry, morphological
      changes and protein analysis were determined by means of electron microscope
      techniqueand immunohistochemical techniquerespectively. RESULT: 50micromol x L(
      1) and 125 micromol x L(-1) of baicalin dose-dependently induced apoptosis and
      inhibited the proliferation of prostate cancer cell DU145 in a dose and time
      dependent manner. DNA flow cytometric analysis indicated that baicalin induced a
      arrest in G1 phase, showing a typical apoptosis peak. Electron microscopy
      detected a characteristic appearance of the apoptotic cells morphology.
      Immunohistochemical analysis revealed that induction of apoptosis by ways of
      inhibition of the bcl-2, loss of the Bax, and upregulation of Fas. CONCLUSION:
      The results indicate that baicalin may induce apoptosis and inhibit proliferation
      of prostate cancer cells, and has direct anti-tumor effects on human prostate
      cancer cells.

PMID- 15714806
TI  - [Exploring relationship between traditional effects of traditional Chinese
      medicine and modern pharmacological activities by "co-effect compounds"].
AB  - The compound that distributes in the herbs with one common effect was named as
      "co-effect compound" (CEC). The CECs of three traditional Chinese medicine(TCM)
      effects, purgative, relieving pain and clearing heat, had been found and studied.
      A strong corresponding relationship was found between the pharmacological
      activities of CECs and the TCM effect they belong to. The study shows that it may
      be a feasible method to connect traditional effect of TCM with modem
      pharmacological activity.

PMID- 15714807
TI  - [Research progress on the oral solid rapidly disintegrating dosage form].
AB  - Oral solid rapidly-disintegrating dosage form has aroused general concern
      increasingly because of its characteristics about convenient taking, rapid
      absorption, high bioavailability and not serious adverse drug reaction. This
      article introduced its mechanism, which was rapid disintegration, fast
      dissolution or the promoting dissolving action of supplementary material. This
      dosage form included dispersible tablets, fast dissolving tablets, fast releasing
      tablets, droppills, granules and tablets by solid dispersible technology, quick
      liquefying chewable tablets and dry elixir. It will become a new way for
      promoting bioavailability in traditional Chinese medicine difficultly-dissolving
      composition, create up a new dosage form for treating emergency case by
      traditional Chinese medicine and give a new thinking for studying new
      supplementary materials. In brief, oral solid rapidly-disintegrating dosage form
      will have good prospect in the field of traditional Chinese medicine.

PMID- 15714808
TI  - [Progress in studies of pharmacological activities and clinical applications of
      preparations of dried leaf of Ginkgo biloba].
AB  - The progress in the research of the pharmacological activities and clinical
      applications of preparations of dried leaf of Ginkgo biloba is summarized. The
      preparations of G. biloba contain various chemical constituents, and have
      activities of relaxing blood vessel, oxidation, improving learning and memory.
      The clinical applications include treatments for coronary heart disease, cardiac
      angina, cerebral infarction, chronic brain syndrome and diabetic nephropathy,
      etc.

PMID- 15714809
TI  - [Studies on the shade-endurance capacity of Glycyrrhiza uralensis].
AB  - OBJECTIVE: To study the shade-endurance property of Glycyrrhiza uralensis and
      provide rationale for the practice of inter-cropping G. uralensis with trees.
      METHOD: Black shading nets were used to provide five different environments of
      light intensities (light penetration rates of 100%, 75%, 65%, 50% and 25%,
      respectively). To assess the shade-endurance capacity of G. uralensis, several
      aspects were evaluated, including growth characters, physiological and ecological
      characters, biomass, and chemical contents. RESULT AND CONCLUSION: G. uralensis
      is a light-favored plant. The growth indices such as plant height, stem diameter,
      leaves number, root diameter, biomass, and daily average photosynthetic rate (Pn)
      are highest when light permeation rate is 100%. All these indices decrease when
      light intensity decreases. However, G. uralensis possesses shade-endurance
      capacity to some degree; it adapts to the shading environment by increasing the
      leaf area and chlorophyll contents. Shading has no obvious effect on the absolute
      light energy utilization rate (Eu) or Fv/Fm ratio. The influence of shading on
      the chemical contents of G. uralensis is obvious.

PMID- 15714810
TI  - [Studies on TLC fingerprint of flavonoids in rhizome of Polygonatum odoratum].
AB  - OBJECTIVE: To study the thin layer chromatographic (TLC) fingerprint of flavonoid
      constituents from Polygonatum odoratum, to set up the identification protocol of
      the herbal and provide scientific information for its quality control. METHOD:
      The ethanol extracts were separated on silica gel G precoated plate with a
      mixture of toluene-ethylacetate-formic acid (5:4:1) as the mobile phase. The
      spots were visualized with ammonia vapor, then were examined under ultraviolet
      light (365 nm). The plate was scanned at wavelengths of lambdaR = 500 nm, lambdaS
      = 280 nm. RESULT: A fingerprint of flavonoids of P. odoratum, with 10 specific
      fluorescent spots while examined under ultraviolet light, was set up. CONCLUSION:
      The method can be used for quality control of P. odoratum.

PMID- 15714811
TI  - [Study on water extraction process of Herba epimedii with microwave technology].
AB  - OBJECTIVE: To study, the high polar media-water extraction process of Herba
      epimedii with the microwave technology. METHOD: The single parameters of
      extraction process was investigated with dry extract yield and extraction
      efficiency of icariin as content index. RESULT: Through studying the single
      parameter, the optimal conditions are as follows: 70% ethanol as wetting solvent,
      volume of solvent to weight of material equal to 6:1 in wetting, 30 min wetting
      time, 2.5 min microwave irradiation time, volume of solvent to weight of material
      equal to 50:1 in extraction process, 10 min microwave-assisted extraction time.
      CONCLUSION: Compared with conventional methods, microwave-assisted extraction
      (MAE) after Microwave Pretreament (MP) of raw material was higher extraction
      efficiency and time-saving.

PMID- 15714812
TI  - [Freeze-drying of silymarin-loaded solid lipid nanoparticles (SM-SLN)].
AB  - OBJECTIVE: To investigate lyophilization of SM-SLN. METHOD: The parameters of
      lyophilization process was optimized. In addition, the protective effect of
      various types and concentrations of cryoprotectants were tested by shape, colour
      and disparity. RESULT: The mixture of 2% lactose and 2% glucose could better
      prevent nanoparticles from aggregating, the optimal lyophilization process was
      followed: precooled at -45 degrees C for 10 hr; primary drying at -25 degrees C
      for 5 hr; secondary drying at 10 degrees C for 3 hr; finally drying at 30 degrees
      C for 6 hr. CONCLUSION: Changes in particle size distribution during
      lyophilization could be minimized by optimizing the parameters of the
      lyophilization process and adding supporting agent.

PMID- 15714813
TI  - [Determination of notoginsenoside R1, ginsenoside Rg1 and Rb1 in Radix
      Notoginseng and its preparation by HPLC-ELSD].
AB  - OBJECTIVE: To establish the quantitative method of notoginsenoside R1,
      ginsenoside Rg1 and Rb1 in Radix Notoginseng and its preparation Xuesaitong
      injection by HPLC-ELSD. METHOD: The column was packed with 5 microm Diamonsil C18
      stationary phase. The mobile phase consisted of acetonitrile-water, eluted in
      gradient mode. The temperature of drift tube was 105 degrees C and the nebulizer
      nitrogen flow rate was 2.9 L x min(-1). RESULT: The linear ranges of the three
      components were 0.456-2.25 microg, 1.47-7.38 microg and 1.20-6.03 microg
      respectively. The average recoveries of the three components in Radix Notoginseng
      were 97.1% (RSD 1.9%), 96.8% (RSD 2.0%), 97.0% (RSD 2.2%) respectively; in
      Xuesaitong Injection were 98.7% (RSD 1.9%), 98.5% (RSD 1.8%), 98.1% (RSD 1.4%)
      respectively. CONCLUSION: It was proved that the method was reliable, simple, and
      precise, that could be used for quality control.

PMID- 15714815
TI  - [Studies on the active constituents in vine stem of Spatholobus suberectus].
AB  - OBJECTIVE: To study the active constituents in vine stem of Spatholobus
      suberectus. METHOD: The constituents of Spatholobus suberectus were
      systematically separated with various chromatographic techniques. The structures
      were elucidated by physico-chemical properties and spectral data. RESULT: Eight
      compounds were isolated from S. suberectus, and were identified as: ononin (1),
      pruneitin (2), gallocatechin (3), catechin (4), epicatechin (5), syringic acid
      (6), vanillic acid (7) and daucosterol (8). CONCLUSION: Compound 3, 4, 6, 7 were
      obtained from Spatholobus genus for the first time. Compound 4 has stimulation to
      proliferation of hematopoietic progenitor cell.

PMID- 15714814
TI  - [Studies on the system for the exclusive control substance in traditional Chinese
      herbal medicines].
AB  - OBJECTIVE: To establish the system for the exclusive control substance of plant
      drug (CSPD) in traditional Chinese herbal medicines (TCHM) for the purpose of
      original identification. METHOD: Three kinds of representative TCHMs were
      selected and their exclusive CSPDs were obtained by standardized procedure. The
      expression of the total chemical characteristic of the CSPDs were achieved with
      the comparative analysis of the 1H-NMR spectra for the CSPDs of the samples of
      the same species collected from different regions as well as the isolation and
      elucidation of the chemical constituents. RESULT: The 1H-NMR spectra of the CSPDs
      for three kinds of representative TCHMs have highly characteristic features and
      reproducibility, and showed mainly the resonance signals of the characteristic
      constituents of each species. These 1H-NMR spectra were strictly correlative with
      the origin of the species. CONCLUSION: By using the procedure of this paper, the
      exclusive CSPDs can be obtained for most of TCHMs, which have important
      significance and can be regarded as references in the original identification of
      TCHMs.

PMID- 15714816
TI  - [Studies on the chemical constituents in herb of Ranunculus sceleratus].
AB  - OBJECTIVE: To isolate and determine the chemical constituents from Ranunculus
      sceleratus. METHOD: Six compounds were isolated and purified by extraction and
      different kinds of column chromatography. The structures were determined on the
      basis of extensive spectral analysis such as EI-MS, 1H-NMR, 13C-NMR, DEPT and
      NOEDS. RESULT: The structures were elucidated as stigmasta-4-ene-3,6-dione I,
      stigmasterol II, isoscopoletin III, scoparone IV, protocatechuic aldehyde V and
      protocatechuic acid VI, respectively. CONCLUSION: Compound I, III, IV, V and VI
      were isolated from R. genus for the first time.

PMID- 15714817
TI  - [Studies on the flavonoid constituents in herb of Eremosparton songoricum].
AB  - OBJECTIVE: To study the chemical constituents from Eremosparton songoricum.
      METHOD: The compounds were isolated with silica gel column chromatography and the
      structures of these compounds were elucidated by means of spectral analysis.
      RESULT: The seven compounds were identified as: 5,7,4'-trihydroxyflavone
      (apigenin) (I), 5-hydroxy-7,4'-dimethoxyflavone (II), 5,7-dihydroxy-3',4'
      dimethoxyflavone (III), 5,7-dihydroxy-4'-methoxyflavone (acacetin) (IV), 5,7,4'
      trihydroxy-3'-methoxyflavone (chrysoeriol) (V), 5,6,3',4'-tetrahydroxy-7
      methoxyflavone (pedalitin) (VI) and 5,4'-dihydroxy-7,3'-dimethoxyflavone-4'-O-D
      glucoside (flavogadorinin) (VII). CONCLUSION: These constituents were obtained
      from E. songoricum for the first time.

PMID- 15714818
TI  - [Study on the interactions between Ligusticum chuanxiong extract and cardiac
      muscle membrane receptors by CMSP chromatography].
AB  - OBJECTIVE: To study the interactions between Ligusticum chuanxiong Hort extract
      and cardiac muscle membrane receptors. METHOD: The cell membrane of rabbit
      cardiac muscle was fixed on silicon to make cell membrane stationary phase
      (CMSP), and then the interactions were studied by comparing the retention
      characteristics of the extracts from different solvents with those of the
      antagonists or activators corresponding to known receptors in cardiac muscle
      membrane, and by competition effect on the retention characteristics of extracts
      when adding the antagonists or activators into the mobile phase. RESULT: Water
      extract and ethanol extract both had retentions on CMSP; the retention
      characteristics of water extract could be affected when water extract was in
      competition with the antagonists for alpha receptor, and could not be affected
      when with the activator beta1 receptor. CONCLUSION: It is possible that some
      components in water extract may combine with alpha receptor and no component with
      beta1 receptor, and that some components in ethanol extract may combine with
      cardiac muscle cell membrane. The process between active components and receptors
      in vivo can be imitated through the interactions between drugs and CMSP. The
      method provides references for the resolution of two applications: to screen the
      active components from Chinese medicine, and to figure out the type of receptors
      involved.

PMID- 15714819
TI  - [Pharmacokinetics of oxymatrine and its metabolite in beagle dogs by LC-MS].
AB  - OBJECTIVE: To establish LC-MS method in the determination of oxymatrine and its
      metabolite in plasma and investigate their pharmacokinetics in beagle dogs.
      METHOD: Lichrospher C18 column (4.6 mm x 250 mm, 5 microm) was used as the
      analytical column maintained at 25 degrees C. The mobile phase consisted of 10
      mmol x L(-1) CH3COONH4 and CH3OH (25:75). Flow rate was 1 mL x min(-1).
      Electrospray ionization (ESI) was carried out. The ESI ion source was set in
      positive ion polasity mode. The selective ion monitoring (SIM) was set at m/z
      265.1 and 249.2. RESULT: The linearity ranged from 2 to 5000 ng x mL(-1) (r =
      0.9991). The detection of oxymatrine and its metabolite were 0.6 and 0.3 ng x mL(
      1). The RSD(%) within day and between day was less than 4.7%. The recovery of
      this method was more than 96.5%. The disposition was conformed to a two
      compartment model. The T(1/2), Tmax, Cmax, MRT, AUC(0-->24 h) of oxymatrine were
      (5.5+/-1.58) h, (1.0+/-0.30) h, (2418.3 +/-970.78) ng x mL(-1), (3.2+/-0.64) h,
      (5797.4+/-908.16) ng x mL(-1) x h accordingly. The corresponding T(1/2), Tmax,
      Cmax, MRT, AUC(0-->24 h) of matrine were (9.8+/-2.77) h, (1.9+/-1.09) h,
      (1532.4+/-494.86) ng x mL(-1), (4.4+/-1.97) h, (5530.5+/-1042.65) ng x mL(-1) x
      h. CONCLUSION: This assay was highly sensitive, rapid, simple and specific enough
      for determining concentrations of oxymatrine and its metabolite matrine in plasma
      of beagle dog.

PMID- 15714820
TI  - [Realgar nano-particles induce apoptosis and necrosis in leukemia cell lines K562
      and HL-60].
AB  - OBJECTIVE: To examine the growth-inhibitory, apoptosis- and necrosis-inducing
      effects of realgar nano-particles (RNP) in human chronic myelogenous leukemia
      cell line K562 and acute myeloid leukemia cell line HL-60, and to find out the
      chemical species with efficacy. METHOD: A "solvent-relay" strategy was used for
      the preparation of RNP suspension. Cell viability was determined by MTT assay.
      Cell apoptosis and necrosis were characterized with Annexin V-PI double staining
      in association with flow cytometry and with morphological examination with
      Hoechst 33258 staining. Parallel experiments with arsenous acid (H3AsO3), the
      dominant form of arsenic trioxide in the solution, were conducted for comparison.
      RESULT: The mean diameter of RNP was 159.0 nm. RNP showed growth-inhibitory
      effect on both cell lines. The double staining test indicated that RNP induced
      both apoptosis and necrosis, and this was further confirmed by morphological
      examination. CONCLUSION: RNP induced both apoptosis and necrosis in leukemia cell
      lines K562 and HL-60. Thioarsenite species with both As-O and As-S bonds may be
      the active intermediates in the RNP.

PMID- 15714821
TI  - [Effects of Tianzhi Keli on extracellular acetylcholine and catecholamine levels
      in striatum of rats with neuromitochondrial impairment].
AB  - OBJECTIVE: To investigate the effects of Tianzhi Keli (TZ) on acetylcholine (ACh)
      and catecholamine levels in striatum of rats with neuromitochondrial impairment,
      and try to find out the neuroprotective mechanism of TZ. METHOD: The
      microdialysis and high performance liquid chromatography (HPLC)-post column
      Immobilized enzyme reactor (IMER)-electrochemical detection (ED) were used to
      establish a model of mitochondrial energy metabolism impairment which induced by
      perfusion with sodium azide (NaN3), and measure continuously the effects of TZ on
      extracellular ACh, choline (Ch) and catecholamine of model rats. RESULT: After
      perfusion with NaN3, ACh, noradrenalin (NE), adrenaline (E), dopamine (DA), 3,4
      Dihydroxyphenyl-aletic (DOPAC), and homovanillic acid (HVA) levels were decreased
      obviously (P < 0.05-0.01), while Ch level was increased distinctly (P < 0.01).
      Transmitters levels were recovered individually after stop the perfusion with
      NaN3. TZ can postpone the decrease of ACh and advance the recover of Ch. The
      effect of TZ coupled with duxil on increasing ACh level is more obviously than
      effect of TZ or duxil. TZ is also showing a tendency to postpone the decrease of
      catecholamine and advance its recovery. TZ coupled with duxil can advance the
      recovery of DOPAC and adjust the metabolic abnormity positively. CONCLUSION: TZ
      has effect on protecting impairment of choline neurosystem, which induced by
      damage of mitochondrion and abnormity of energy metabolism; coupled with duxil
      have synergistic action. TZ also has tendency to protect the impairment of
      epinephrine and dopamine neurosystem.

PMID- 15714822
TI  - [Effects of processing Phellodendron amurense with salt on anti-gout].
AB  - OBJECTIVE: To investigate the effects of processing Phellodendron anurene with
      salt on anti-gout. METHOD: The mouse serum uric acid level and liver xanthine
      oxidase activity were used to evaluate anti-gout effects of raw and processing P.
      amurense with salt. RESULT: Both raw and processing P. amurense with salt reduced
      serum uric acid levels in the in hyperuricemic mice, and inhibited activities of
      liver xanthine oxidase at the low and high doses respectively, thus exhibiting
      anti-gout effects. Moreover, they showed the tendency to decrease the uric acid
      levels in the normal animal only at the high dose. The latter was a little weaker
      than the former. CONCLUSION: Processing with salt might not significantly change
      anti-gout effect of P. amurense.

PMID- 15714823
TI  - Senate Majority Leader Sikkema: Medicaid needs a cap.

PMID- 15714824
TI  - Reinvent the wheel.

PMID- 15714825
TI  - Maintaining standards of professionalism.

PMID- 15714826
TI  - Asking about and treating HIV-positive patients.

PMID- 15714827
TI  - Build your practice by giving your expertise away.

PMID- 15714828
TI  - Important reasons to stay with the MDA health plan.

PMID- 15714829
TI  - The evolution of "baby teeth".

PMID- 15714830
TI  - Current concepts in vital pulpotomies in primary teeth.
AB  - Vital pulpotomies in primary teeth are performed to maintain the vitality of the
      pulp and to hold the tooth until it can be normally exfoliated. There exists much
      controversy surrounding the issue of pulpotomy agents, and the ideal pulp
      dressing material has not yet been identified. Therefore, it seems that
      formocresol will still be the first choice for pulpotomies in primary teeth until
      such agent is identified.

PMID- 15714831
TI  - Stainless steel crowns: consider them in your office.

PMID- 15714832
TI  - Full-coverage restorations of primary anterior teeth.

PMID- 15714833
TI  - Let's all "Give Kids a Smile"!

PMID- 15714834
TI  - My best friends: beer and marijuana. One dentist's personal story.

PMID- 15714835
TI  - [Tobacco abuse in pregnancy].

PMID- 15714836
TI  - [Psychodiagnostic instruments for the assessment of autism spectrum disorders].
AB  - OBJECTIVES: Established scales for the early detection and general diagnostics of
      autism will be reviewed with a focus on the instruments available in German.
      METHODS: All questionnaires, observation scales and interviews for the assessment
      of autism and associated conditions found in a search of Medline, PsychInfo,
      Psyndex and Google up to May 2004 are quoted. Instruments adapted and developed
      for the German-speaking countries are presented in more depth. RESULTS: An
      increasing number of reliable national and international scales for the
      assessment of disorders of the autism spectrum are available. Currently a
      combination of the Social Communication Questionnaire (SCQ), the Autism
      Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview
      Revised (ADI-R) is regarded as the standard for a psychometrically based
      diagnosis of autism. CONCLUSIONS: For certain diagnostic groups and issues there
      continues to be a need for German-language instruments. Particularly scales for
      the assessment of the broader phenotype of autism, as well as instruments that
      are more sensitive to change would be desirable for outcome measurement and
      intervention evaluation.

PMID- 15714837
TI  - [The Marburg Rating Scale for Asperger's Syndrome (MBAS)--a screening instrument
      for high-functioning autistic disorders].
AB  - OBJECTIVES: Asperger's Syndrome is a disorder of uncertain nosological validity,
      which is difficult to differentiate from high-functioning autism. Even today
      these disorders are unfortunately diagnosed very late, often in the wake of
      earlier, different diagnoses. The purpose of this study is to present a screening
      instrument (MBAS), which is sensitive to these disorders. METHODS: The instrument
      was tested among a total of 91 probands (44 of whom had been diagnosed as
      autistic, and 47 of whom had been diagnosed with a non-autistic disorder).
      RESULTS: The items on the MBAS were of average difficulty; generally, the all
      item-total correlation was good. The total scale has an internal consistency of
      Cronbach's alpha = .91 and the convergent validity of the MBAS and the ADI-R
      reached r = .61 (p = .001). The total score of the questionnaire discriminated
      highly significantly between the group with autism and that without. At a
      sensitivity of 95.5% and a specificity of 95.7% the number of misclassifications
      is low. False negative classifications occurred only in the case of very young
      children. CONCLUSIONS: The MBAS is a reliable and valid instrument for screening
      and generating tentative diagnoses of high-functioning autism. The questionnaire
      is well suited for the selection and generation of tentative diagnoses of autism
      on a high-functioning level.

PMID- 15714838
TI  - [Validation of the German version of the Australian Scale of Asperger's Syndrome
      (ASAS)].
AB  - OBJECTIVES: The aim of the study was to validate the German version of the
      Australian Scale for Asperger's Syndrome (ASAS). Furthermore, the scoring of the
      ASAS as applied by the Australian authors was verified. METHODS: The mothers of
      18 children with Asperger's Syndrome, those of 18 children referred for a
      possible diagnosis of Asperger's Syndrome, but who did not receive that
      diagnosis, and the mothers of 15 children with other mental disorders
      participated in the study. All of the children were inpatients at the University
      of Wuerzburg Hospital of Child and Adolescent Psychiatry. RESULTS: According to
      an analysis of variance, the scale successfully differentiates among the three
      samples. A stepwise discriminant analysis was performed. Classification results
      show that the membership of the three groups could be labelled accurately
      (accuracy rate: 60.78%). The ASAS's scoring methodology appears to yield good
      results for German patients. CONCLUSIONS: The scale appears to be an adequate
      tool for screening purposes in that it correctly discriminates children and
      adolescents with Asperger's Syndrome.

PMID- 15714839
TI  - [Hans Asperger and his patients--a retrospective examination of the spectrum of
      autistic disorders].
AB  - In 1944 the Viennese paediatrician Hans Asperger described for the first time a
      number of boys with so-called "autistic psychopathy" but failed to give a
      detailed quantitative-descriptive phenomenology of the condition. The aim of this
      second part of a retrospective analysis of the clinical case records of children
      diagnosed by Asperger and his team is to provide a quantitative, in-depth
      description of these children, as well as to investigate Asperger's idea of a
      transition from autistic psychopathic personality traits towards "normality". We
      examined 181 case records of children seen between 1950 and 1986 who were either
      clearly diagnosed with autistic psychopathy (AP) or showed autistic features
      (AZ). Consequently, features common to both the AP and AZ groups and the
      differences between them are described and compared to the current ICD-10
      criteria for Asperger's syndrome. Children with AZ shared the high intelligence,
      the social handicap and the impairment of "instincts", but showed less severe
      symptoms and more distinct skills, as well as fewer co-morbid disorders than
      children with AP. Results suggest that there is indeed something like an
      "autistic phenotype" with certain deficits and assets that can be found in less
      handicapped children with autistic impairments. The current ICD-10 criteria do
      not seem to fully capture Asperger's original account of the syndrome and should
      be discussed anew if Asperger's syndrome is reconsidered for inclusion into
      diagnostic criteria in the future.

PMID- 15714840
TI  - [Development and evaluation of a psychoeducational group training programme for
      teachers of autistic pupils with mental retardation].
AB  - OBJECTIVES: Teachers of autistic pupils show profiles of increased stress that
      are caused by the social, communicational, and cognitive deficits of these
      children. The aim of the present study was to develop and evaluate a psycho
      educational group training programme for teachers. METHODS: The curriculum
      covered theoretical issues of autism as well as educational skills focusing on
      "structured teaching" (TEACCH: Schopler, 1997). The training outcomes were
      evaluated within a pre-post (9 months) design. A total of 10 teachers working
      with 10 autistic children (mean age: 10 years) from schools for mentally retarded
      pupils participated in the training programme which included three one-day group
      sessions followed by six half-hour individual training sessions in the classroom
      (over a period of six months). The outcome variables were measured by means of
      teacher questionnaires assessing child behavioural symptoms, teachers' stress
      reactions, effects on the teachers' psychological adaptation, teacher-student
      interaction and implementation of methods. RESULTS: The training programme
      resulted in significant effects (p < 0.5) on child symptoms as well as on
      teachers' stress reactions. In addition, the teachers' psychological adaptation
      and teacher-student-interaction improved. On average, teachers implemented about
      two structured teaching methods. CONCLUSIONS: These findings indicate some
      evidence for the clinical validity of the teacher training procedure examined,
      taking into consideration some methodological limitations.

PMID- 15714842
TI  - [Comments regarding various general considerations on the daily practice of
      urology...].

PMID- 15714841
TI  - [Treatment effects of parent management training for ADHD].
AB  - OBJECTIVES: The study investigated the efficacy of a programme of parent
      management training in groups for the parents of ADHD children that is based on a
      cognitive behavioural concept. METHODS: The parents of 16 ADHD children
      participated in group training over a ten-week period. Children were medicated
      with methylphenidate and received consultations. 17 other ADHD children (control
      group) benefited only from medication with methylphenidate plus consultation;
      however, their parents did not participate in any group training. In both groups,
      assessment was done by means of parent questionnaires: in the experimental group
      to assess the core symptoms of ADHD, homework problems and global problems that
      occur in families with ADHD; in the control group to assess only the core
      symptoms of ADHD. RESULTS: The training significantly reduced core symptoms of
      ADHD, homework problems and global problematic situations in the experimental
      group. In comparison to the control group, the core symptoms of ADHD decreased
      more strongly in the experimental group. This effect failed to reach the
      significance level of p < 0.05 (Mann-Whitney U-test). However, the verification
      with the linear model showed a significant difference between the two groups on
      the factor "hyperactivity index". CONCLUSIONS: Parent management training in
      groups was a useful adjunct in the treatment of ADHD children.

PMID- 15714844
TI  - [Cryobiology and pathologic lesions induced by freezing-thawing processes in
      prostatic tissue. Second part].
AB  - Cryosurgery is an emerging technology consisting on controlled freezing of
      tissues. Good results, maintained in the long-term, have been referred in the
      treatment of prostate adenocarcinoma. A role as possible substitute of partial
      nephrectomy in the treatment of renal adenocarcinomas smaller than 4-5 cm is
      under research. There is no discussion that freezing destroys cellular machinery
      and triggers several events the final result of which is cell death by necrosis
      and apoptosis. The decrease of temperature makes extracellular liquid crystallize
      and creates a hyperosmotic environment, which induces water to go out of the cell
      producing intracellular dehydration. Intracellular ice is created with fast
      freezing speeds being attributed the most destructive effect on biological
      tissues with irreparable damage. In blood vessels, it directly induces
      endothelial cell death and mechanical lesions of the endothelium; the consequence
      is the formation of thrombi that obstruct the lumen of the vessel. In the post
      thawing phase there is an increase in free radicals formation and neutrophil
      activity, which induces cellular membrane lipids peroxidation and new endothelium
      lesions. Tissue destruction is determined by: minimal temperature achieved,
      freezing speeds, freezing phase duration, number of freezing-thawing cycles
      provided, and distance to the freezing focus. As we move away from the freezing
      focus cells are affected in different ways, and there are several mechanisms
      proposed to explain the lethal action induced by temperatures higher than--40
      degrees C. In our series pathologic findings were: necrosis, hemorrhagic areas
      either developed or not, fibrosis, hyalinization and increases in the relative
      number of hematic capillaries, microscopic calcifications, basal cells
      hyperplasia, and transitional or squamous metaplasia. Residual cancer is
      localized in the areas less affected by freezing. It should be emphasize the
      scarce morbimortality associated with the procedure. It does not require ICU
      admission or blood transfusions, no cerebral vascular accidents (CVA) or heart
      events have been described, and mortality is null, so that it is feasible in high
      surgical risk patients and without age limit.

PMID- 15714843
TI  - [Alfredo Tramoyeres Cases (1910-2002): first chairman of the Department of
      Urology at the Ciudad Sanitaria La Fe. Documentary-historical analysis of his
      works].
AB  - OBJECTIVES: Urology, having been part of general surgery for centuries, was
      completely consolidated as a medical speciality in the middle of the XX Century
      as the result of years of evolution and development, and all the studies and
      works of certain authors that represent today the mainstays of our speciality.
      Valencia in the middle of the 20th century saw the birth of new hospitals
      including the "Ciudad Sanitaria La Fe". Alfredo Tramoyeres Cases was the first
      chairman of the Department of Urology. This article reviews his long and fertile
      professional life. METHODS: We have reviewed all his scientific works. The
      articles have been obtained from Medicina Espanola, Revista Espanola de Cirugia
      Traumatologica y Ortopedia, and Archivos Espanoles de Urologia. His most
      important urological work is his doctoral thesis with the title "Sigmoid-procto
      ureterostomy: personal modification" published in Valencia in 1976. For his
      biography we used the" Biographic and bibliographic history of the Spanish
      Urology over the XX century" and interviews with family members. RESULTS: We
      emphasize his thorough description of the various types of urinary diversion. He
      covers the topics of bladder diverticula and bladder neck disorders, in which he
      supports surgical treatment. Finally, he sets out the rupture of the posterior
      urethra and various treatments for prostate cancer at that time. CONCLUSIONS:
      Alfredo Tramoyeres Cases contributed to the definitive consolidation of our
      speciality in the area of Valencia during the second half of the XX century,
      through his long professional life, with his interesting scientific
      contributions.

PMID- 15714845
TI  - [Living donor nephrectomy for kidney transplantation. Experience in the first two
      years].
AB  - OBJECTIVES: Laparoscopic surgery offers potential advantages in terms of
      diminishment of postoperative pain, shorter hospital stay, faster convalescence,
      and better cosmetic results. These advantages may increase kidney donation,
      making donation be accepted by more candidates. We report our first 2 years'
      experience with laparoscopic donor nephrectomy METHODS: Between March 2002 and
      February 2004 we performed 38 laparoscopic living donor nephrectomies for kidney
      transplantation. The technique of choice was the transperitoneal laparoscopic
      approach with four trocars, usually three of them from the start of the procedure
      -two 10-12 mm and one 5 mm--, and a 6.5 cm perumbilical midline incision for
      kidney retrieval at the end of the procedure. RESULTS: Receptor and donor
      survivals were 100%. Graft survival was 97.6%. There was not any case of delayed
      graft function. Donor: Mean operative time was 161 minutes (115-260). Mean
      estimated blood loss was 270 ml (100-1200). Three patients required blood
      transfusions, 2 units of packed red blood cells each. Mean hospital stay was 5.1
      days (3-11). Mean warm ischemia time was 3.2 min. (2-10). Conversion to open
      surgery was necessary in four cases. Receptor: there have been three significant
      complications requiring surgical repair: one case of low arterial flow, one
      vesico ureteral leak, and one midurethra stenosis. Initial renal function: mean
      serum creatinine at one month was 147mmol/l, with a trend to improve to 126
      mmol/l at one year, which is considered optimum. First postoperative day mean
      serum creatinine was 192mmol/l and the nadir was on second postoperative day with
      a value of 152mmol/l. CONCLUSIONS: We believe laparoscopic living donor
      nephrectomy is a real alternative to open surgery because it offers better
      recovery to the donor with the same capacity to preserve renal function in the
      receptor.

PMID- 15714846
TI  - [Laparoscopic pyeloplasty. Our experience].
AB  - OBJECTIVES: To report our experience with laparoscopic pyeloplasty in the
      treatment of pyeloureteral junction obstruction. METHODS: Between August 2001 and
      August 2004 14 patients with the diagnosis of pyeloureteral junction obstruction
      underwent laparoscopic repair. Seven cases had the obstruction on the left side
      and the other seven on the right side. We describe the technique of laparoscopic
      dismembered Anderson-Hynes type pyeloplasty, performed to 12 patients in our
      series. The remainder 2 patients underwent Foley's Y-V plasty and the Fenger's
      technique. RESULTS: Mean operative time was 199.7 minutes (r: 126-290). There
      were not intraoperative complications. Mean hospital stay was 4.63 days (r: 3-9).
      One case of double J catheter obstruction can be cited as late postoperative
      complication. Only one of the 14 cases suffered a recurrence of the stenosis
      after double J catheter retrieval. CONCLUSIONS: Laparoscopic pyeloplasty has
      become the operation of choice in cases of hydronephrosis secondary to crossing
      vessel, when there is great pyelic dilation, and for the treatment of failures of
      previous endopyelotomy.

PMID- 15714847
TI  - [Intergamete complementarity: short review].
AB  - OBJECTIVE: The aim of this review is to recognize the role of molecules involved
      in intergamete interactions during the process of fertilization and further
      understanding of the molecular basis of fertilization in humans for the
      development of new methods for contraception. METHODS: We carried out a
      bibliographic review on intergamete interactions. RESULTS: Fertilization is the
      product of a series of ordered steps that must take place both in the sperm and
      the oocyte for a correct interaction leading to the development of the new
      individual; this interaction requires that both cells are in perfect state for
      recognition to occur; this recognition is dependant on terminal oligosaccharide
      residues present in zona pellucida and their complementary receptors on sperm
      plasmatic (primary receptors) and inner acrosomal (secondary receptors)
      membranes. CONCLUSIONS: Knowledge of these processes will provide a better
      understanding of the molecular mechanisms in intergamete interaction and could
      lead to the development of tools for controlling reproduction as well as for
      helping couples presenting alterations of their

PMID- 15714848
TI  - [Initial experience with radiofrequency percutaneous ablation of renal tumors].
AB  - OBJECTIVES: To evaluate the usefulness of percutaneous or laparoscopic
      application of radiofrequency for ablation of tumoral tissue in patients with the
      diagnosis of solitary renal tumor. METHODS: 3 male patients (one with bilateral
      renal tumor) underwent 4 radiofrequency ablation treatments (1 laparoscopic, 3
      percutaneous) for renal masses between 1.5 and 5 cm (average 3.15 cm).
      Percutaneous approach was gained under ultrasound control. Energy was applied
      progressively, following standardized tables, requiring between 2 (tumor diameter
      1.5 cm) and 4 cycles (diameter 5 cm) applied in quadrants. Postoperative control
      was performed in all cases by IV contrast helical CT scan. RESULTS: Treatment was
      completed in all cases. In one case, laparoscopic tumorectomy was also performed.
      Radiofrequency cycles oscillated between 30 and 19 minutes depending on tumor
      size. There were not procedure-derived complications. IV contrast CT scan
      controls at 3 and 6 months showed absence of tumor in one case (1.5 cm) and
      absence of intratumoral contrast uptake in the rest of them. CONCLUSIONS:
      Radiofrequency ablation of small renal tumors, either percutaneous or
      laparoscopic, is a well-tolerated and minimally invasive procedure. Adequate
      parameters to consider complete tumor tissue destruction remain to be determined
      and validated.

PMID- 15714849
TI  - [Cystic hamartoma of the renal pelvis: unfrequent finding].
AB  - OBJECTIVES: This cystic hamartoma of the renal pelvis is a very unfrequent benign
      tumor. We report one case emphasizing its histology and performed a bibliographic
      review. METHODS: Mid age female patient with the incidental diagnosis of a renal
      mass taking up the pelvis. RESULTS: A radical nephrectomy was performed with the
      pathologic report of cystic hamartoma of the renal pelvis. CONCLUSIONS: It is a
      cystic renal tumor with well-defined histologic and immunohistochemical criteria,
      and it probably does not involve any danger for the patient's live.

PMID- 15714850
TI  - [Bladder metastasis of renal carcinoma].
AB  - OBJECTIVES: We report the case of a patient who had underwent surgery for a clear
      cell renal carcinoma 2 years before presenting with metastasic extension to
      bladder on follow-up. METHODS: Radiological finding of a bladder mass during
      follow-up after nephrectomy. RESULTS: TURBT was carried out with the pathologic
      report of clear cell carcinoma, compatible with a primary renal origin.
      CONCLUSIONS: Bladder is a very rare place for metastasis from kidney tumors.
      Prognosis will depend on the time of appearance of such metastases.

PMID- 15714851
TI  - [Metacronous transitional cell carcinoma of the prostatic urethra in a patient
      with history of nephroureterectomy for upper urinary tract urothelial tumor].
AB  - OBJECTIVES: We report one case of Metacronous transitional cell carcinoma (TCC)
      of the prostatic urethra in a patient with history of left nephroureterectomy 22
      years before for urothelial neoplasia of the upper urinary tract. METHODS: We
      describe the case of a 56-year-old male patient who presents with
      oligosymptomatic hematuria for several months. Cystourethroscopy showed irregular
      hyperemic lesions in the prostatic urethra, cold biopsy of which showed
      urothelial atypia. Pathology report of fragments of a posterior transurethral
      resection (TUR) was compatible with high-grade superficial transitional cell
      neoplasia. Instillation of Bacillus Calmette-Guerin (BCG) was indicated.
      Reevaluation TUR was performed. RESULTS: Pathologic report of new samples showed
      TCC infiltrating the prostatic stroma. The extension study showed ilioobturator
      adenopathies. Chemotherapy did not achieve significant results. Radical surgery
      was rejected. CONCLUSIONS: We emphasize the notable metachronous character of the
      transitional cell carcinoma of the prostatic urethra with respect to the upper
      urinary tract TCC. We also point out the metastasic capacity of these neoplasias,
      as well as the bad prognosis of those cases in which chemotherapy is not
      effective.

PMID- 15714852
TI  - [Obstructive urethral angioleiomyoma].
AB  - OBJECTIVES: To report one case of urethral angioleiomyoma because of the rare
      site, and to review its main characteristics. METHODS: We report one case of male
      urethra angioleiomyoma presenting with obstructive symptoms. RESULTS: We
      performed excision and end to end anastomosis of a small bulbar urethra stenosis.
      Pathology reported angioleiomyoma. CONCLUSIONS: Angioleiomyoma is a benign tumor
      arising from smooth muscle within blood vessel walls. It is extremely rare in the
      urethra. It is more common in females. Recurrence and metastasis are exceptional.
      It shows scarce or moderate cellularity with predominance of fusiform cells. They
      may express smooth muscle vimentin, desmin, and actin. The best therapeutic
      option is resection.

PMID- 15714853
TI  - [Renal brucelloma: an exceptional pathology].
AB  - OBJECTIVES: To report one case of renal brucelloma, an extraordinarily rare
      pathology in our environment. METHODS: 51-year-old completely asymptomatic
      patient who was referred from his primary care physician for the study of a
      calcified image on the right renal area discovered in a x-ray control. RESULTS:
      Radiological studies (US + CT scan + IVU) showed an irregular calcified mass in
      the lower pole of a non-functional right kidney. Microbiological diagnosis was
      negative. Radical nephrectomy was performed. Purulent material came out from the
      kidney during the operation, which cultured (+) to Brucella Melitensis.
      Pathologic study was compatible with renal brucelloma. CONCLUSIONS: Genitourinary
      involvement by Brucella is second in frequency after osteoarticular, being
      orchyoepididymitis the most common clinical presentation, followed by
      prostatitis. Renal involvement is exceptional.

PMID- 15714854
TI  - [Adenoid cystic carcinoma of the prostate].
AB  - OBJECTIVES: To report a new case of adenoid cystic carcinoma of the prostate.
      METHODS: We evaluated clinical presentation, diagnosis, treatment and evolution
      of a 68-year-old patient with an adenoid cystic carcinoma of the prostate.
      RESULTS: The patient did not receive any of the treatments suggested by our
      department, having a favourable outcome for 28 months; after this period he
      presented abdominal metastases which where surgically excised. Adjuvant
      radiotherapy was indicated. CONCLUSIONS: The adenoid cystic carcinoma is a rare
      tumor. The treatment of choice of these patients is radical prostatectomy and
      close follow-up.

PMID- 15714855
TI  - [Laparoscopic radical nephrectomy].

PMID- 15714857
TI  - [The best of vascular medicine in 2004].
AB  - The wealth of information in vascular pathology merits close examination. The
      French Cardiology Society vascular group turned its attention to arteries, veins,
      hypertension and a more fundamental investigation to analyse the results from
      some illuminating studies which appeared in 2004, despite some pertinent
      therapeutic doubts. Examination of the trials discussed here shows the
      importance, as much in vascular pathology as elsewhere, of founding our practice
      on evidence based medicine.

PMID- 15714858
TI  - [The best of interventional cardiology in 2004].
AB  - During 2004 the evolution of interventional cardiology has been largely dominated
      by the expansion of activated endoprostheses, whose advantages have been
      continuously shown in several studies and surveys. The extension of new
      indications and the evaluation of new drugs have been witnessed. A new field of
      converging interest has appeared with the very promising treatment for
      valvulopathies, in particular mitral insufficiency and calcified aortic stenosis.

PMID- 15714859
TI  - [The best of nuclear cardiology and MRI in 2004].
AB  - In this review, we limit ourselves to original studies based on scintigraphic or
      MRI techniques performed in man. During the year 2004 we have learned several
      lessons from various interesting studies reported below, regarding different
      areas of cardiology including myocardial ischaemia, myocarditis, myocardial
      infarction and myocardial viability.

PMID- 15714860
TI  - [The best of cardiac failure in 2004].
AB  - Regarding cardiac failure, the year 2004 was notable for the dissemination of
      indications for the use of medical devices in heart failure: indications for
      cardioversion with the long awaited publication of the COMPANION study,
      advancement of the concept of intra-ventricular asynchronism, and studies of
      defibrillators in non-ischaemic cardiac failure (COMPANION, DEFINITE, SCD-HeFT,
      TOVA). Furthermore, pragmatic clinical studies allowed refinement of the uses of
      BNP (diagnostic and prognostic), underlining the importance of renal function and
      its progression during hospitalisation, and the risks of using strong, modern
      therapy in populations without "ad hoc" surveillance which do not correspond with
      study populations (aldactone in Canada). Just as in coronary patients, it appears
      to be important to commence full medical treatment prior to hospital discharge,
      because treatment is rarely changed thereafter. The management of seriously ill
      patients is evolving with several therapeutic advances: the methods of selecting
      patients for heart transplants have changed, with the advancement of
      opportunities for circulatory assistance. Attention has also been turned to the
      significant group, still poorly understood, of patients with diastolic heart
      failure, for whom diagnostic methods have been defined, as well as their clinical
      characteristics. Lastly the medication studies: new drugs in acute cardiac
      failure (preliminary results for vasopressin antagonists), wider indications for
      betablockers in elderly subjects (SENIORS), and advances in cellular
      cardiomyoplasty (using haemopoietic stem cells especially this year). It has been
      a fruitful year, difficult to summarise in a few lines, or even several pages....

PMID- 15714861
TI  - [The best of congenital heart disease in 2004].
AB  - The year 2004 was notable, as were the previous years, for advances in diagnosis,
      treatment and follow-up of certain congenital cardiac diseases with studies
      carried out in the foetus, the child and the adult. Foetal cardiology is in
      constant development: the malformations are better detected, left ventricular
      function is evaluated by echocardiography, and, consequently, foetal cardiac
      failure can be treated. Interventional procedures have started in the foetus with
      results that require confirmation. In children and adults, publications of
      interventional catheterisation are as numerous as before: percutaneous closure of
      atrial septal defects, closure of patent foramen ovale in cases of transient
      ischaemic cerebral attacks, closure of congenital or acquired (iatrogenic, post
      infarct or traumatic) ventricular septal defects, percutaneous valve replacement,
      maintenance of patent ductus arteriosus. Many other interventional procedures
      have been carried out in operated and unoperated congenital heart lesions:
      angioplasty, embolisation, valvular stenosis. Adult congenital heart disease may
      pose problems of arrhythmia, during pregnancy for example. Cardiac
      resynchronisation, which is well developed in adults with cardiac failure, also
      has indications in congenital heart disease of children and adults. Pregnancy is
      possible in women with tetralogy of Fallot, operated or not, with a maternal risk
      of left ventricular dysfunction and progression of pulmonary regurgitation. After
      a Mustard procedure, pregnancy may aggravate symptoms and NYHA Class but it is
      usually well tolerated. Finally, let's cite one publication which showed, if it
      was still necessary, that maternal and foetal risk in pregnancy is high in
      patients with an Eisenmenger syndrome.

PMID- 15714862
TI  - [The best of echocardiography in 2004].
AB  - What major trends can we single out from the large amount of literature that
      appeared in 2004? The role of echography in the investigation of asynchronism has
      most certainly been better defined. Real time 3D echography, now routinely
      available, has started to gain respect in different pathologies. The place of
      filling pressure evaluation in patients' management, as much diagnostic as
      therapeutic, has again been refined. The prognostic contribution of stress
      echography has been emphasized in particular this year. Despite a still limited
      routine role, publications regarding contrast techniques have been quite
      numerous: not only diagnostic contrast echography, but also contrast and
      pleiotropic gene transfer in the myocardium. The study of coronary reserve via
      the transthoracic route, possibly assisted with contrast, should become
      established as a routine technique.

PMID- 15714863
TI  - [The best of hypertension in 2004].
AB  - Among the major developments of the year 2004 in the knowledge of hypertension, a
      special part should be dedicated to the venue in Paris of the Fourteenth meeting
      of the European Society of Hypertension last June. Beside major progress observed
      in basic science, namely signaling pathways involved in the regulation of smooth
      muscle tone, growth and inflammation, at the cross-road of hypertension,
      diabetes, and metabolic syndrome, large clinical trials have afforded strong
      evidence for the usefulness of lowering blood pressure in various diseases
      associated with hypertension. Despite these advances, the percentage of treated
      hypertensive patients who reach the BP goal (<140/90 mmHg) is too low (about
      30%). Thus urges the need for adapting therapeutic strategies. The ESH meeting
      gave the opportunity to gather a large body of evidence for a better therapeutic
      approach, in order to control BP in a larger number of hypertensive patients.

PMID- 15714864
TI  - [The best of clinical pharmacology in 2004].
AB  - The year 2004 was not marked by major pharmacological advances, but by
      confirmation of previous "evidence". Several innovative drugs for stable angina
      (ranolazine, ivabradine), some interesting results in acute coronary syndrome
      (PROVE IT study), some classic concepts (cannabinoid receptors and their
      antagonists such as rimonabant) applied to novel indications (treatment of
      obesity), hopes for the "sartans" revived in the light of new evidence (VALUE
      study), advances in the management of diabetes and hypertension (ASCOT and CARDS
      studies), nebivolol which is not just a betablocker but also produces the NO
      radical (is this why it decreased the mortality of heart failure in the elderly
      in the SENIOR study?). In contrast, although Chronadalate did not live up to
      expectations for coronary insufficiency, the year was marked above all by the
      much heralded withdrawal of Vioxx for increasing cardiovascular risk. The old
      adage: primum non nocere springs to mind.

PMID- 15714865
TI  - [The best of arrhythmia in 2004].
AB  - As for the preceding years, important studies regarding several remaining
      clinical issues for electrophysiologists have been reported in 2004. Large
      randomized studies have underlined the need for an EP study in asymptomatic
      patients with overt ventricular preexcitation. In addition to a short antegrade
      refractory period, arrhythmia induction (atrial fibrillation or reciprocating
      tachycardia) argues for accessory pathway ablation. Although currently leading to
      fairly good results, atrial fibrillation ablation technique is still evolving.
      Encircling pulmonary vein and the surrounding atrial tissue seems to give better
      long term clinical results as compared to ostial pulmonary vein disconnection.
      Large series have confirmed that whatever cardiomyopathy etiology, prophylactic
      ICD implantation was associated with a reduction of sudden arrhythmic death
      during follow-up in patients with low ejection fraction. However, in order to
      save one patient more and more patients have to be implanted because of the
      increasing efficacy of pharmacological treatment for heart failure. Three
      clinical series of arrhythmogenic right ventricular dysplasia implanted with AICD
      have been published this year. The prognostic factors for the occurrence of
      severe ventricular arrhythmia are hemodynamically ill tolerated ventricular
      tachycardia, and VT induction during EP study. Management of patients with
      Brugada syndrome is still far from being well defined. Interestingly in a recent
      report, hydroquinidine has been found to reduce the incidence of ventricular
      arrhythmia in the follow-up as well as the rate of ventricular arrhythmia
      induction in the EP lab. Yet, prophylactic ICD implantation remains the treatment
      of choice in symptomatic and inducible patients.

PMID- 15714866
TI  - [The best of cardiac pacing in 2004].
AB  - The year 2004 saw the publication of the results of the COMPANION and PAVE
      studies concerning cardiac pacing. The former underlined, if it was still
      necessary, the direct relationship between pacing and rhythmology in terms of
      sudden death due to rhythm disturbances in cardiac failure. COMPANION attempted
      to discover whether, in severe cardiac failure with intraventricular conduction
      defects, the addition of multisite pacing either with or without defibrillation
      is liable to alter the combined risk of death and hospital episodes compared with
      optimal drug therapy alone. This study confirmed the advantages of
      resynchronisation pacing already observed in MUSTIC, MIRACLE, InSync and CONTAK
      CD: retarded progression of cardiac failure, reduction in the number of
      hospitalisations and functional improvement. Adding defibrillation to anti
      bradycardial resynchronisation pacing improved the survival, but only slightly
      so. On the other hand, the size of the subgroups did not allow any conclusions to
      be drawn about function and aetiology of cardiac failure, whether ischaemic or
      not. The PAVE study allowed comparison between biventricular pacing and right
      ventricular pacing alone in patients in NYHA class II or III, with atrial
      fibrillation for more than one month and having undergone elective ablation of
      the nodo-Hissian pathway. The results gave confirmation of the harmful effects of
      pacing at the apex of the right ventricle in pacing-dependent patients. On the
      technological front, there was confirmation that probes designed for left
      ventricular stimulation are stable and increasingly easy to use thanks to a new
      configuration and the use of bipolar. Finally, telecardiology has started to
      proliferate and evaluation of its applications is under way, even though its
      clinical use is confirmed on a daily basis.

PMID- 15714867
TI  - [The best of thrombosis in 2004].
AB  - The optimal pharmacological antithrombotic treatment for interventional coronary
      procedures is a controversial subject. The ISAR-REACT trial investigated the
      necessity of a IIb/IIIa glycoprotein inhibitor in procedures not considered at
      high risk, that is to say excluding acute coronary syndromes, and concluded that
      there was no additional gain with this treatment compared with placebo when the
      patient was pre-treated with 600 mg of clopidogrel. The REPLACE-2 trial proposed
      an alternative to a treatment with NFH and IIb/IIIa glycoprotein inhibitor with
      the use of a direct antithrombin, bivalirudine. Heparin therapy of acute coronary
      syndromes and the eventual ensuing interventional coronary procedure may employ
      NFH or LMWH. New large scale trials (SYNERGY and phase A of the so-called A to Z
      trial) compared the two approaches and are reported later on. If facilitated
      angioplasty is a seductive concept, the best antithrombotic association remains
      to be determined (BRAVE trial). Bitherapy with a platelet inhibitor and an
      antithrombotic, ximegalatran, was tested in the ESTEEM trial and in the post
      infarct period. Bitherapy with platelet inhibitors clopidogrel and aspirin versus
      clopidogrel alone was tested in patients with "ischaemic" stroke but does not
      seem to be more effective than monotherapy. In pulmonary embolism, the
      fondaparinux seems to be an alternative to NFH. Finally, the concept of
      resistance to platelet inhibitors is in vogue and is the subject of some
      interesting trials.

PMID- 15714868
TI  - [The best of valvular heart disease in 2004].
AB  - The year 2004 was rich in publications concerning valvular heart disease.
      Infectious endocarditis was the subject of guidelines on prevention, diagnosis
      and therapeutic management under the aegis of the European Cardiology Society.
      There was much study on aortic pathology: the results appear to slow the
      progression of the severity of aortic stenosis. Furthermore, MRI can be advocated
      when there is a conflict in the measurement of the aortic area in aortic stenosis
      as determined by non invasive methods. This year was also marked by the first
      experiences of transcutaneous implantation of a prosthetic aortic valve in
      patients considered inoperable. Mitral insufficiency has also been studied:
      operative indications, incidence and prognosis of early and late post-operative
      atrial fibrillation and the significance of ischaemic mitral insufficiency, for
      which the prognosis remains poor. Lastly, the diagnosis and management of
      prosthesis thrombosis were studied and in particular the contribution of
      thrombolysis. Of course, this analysis is limited, and many studies have not been
      included in this selection.

PMID- 15714869
TI  - The effects of combined liquid and membrane barriers in prevention of post
      operative intra-abdominal adhesions after experimental jejunal anastomosis in
      dogs.
AB  - The study was carried out on 40 apparently clinical healthy dogs classified into
      5 groups of 8 dogs each. Adhesion was experimentally induced by transsection and
      reanastomosis of jejunum. In the control group the site of anastomosis and
      abdominal cavity was lavaged with 250 ml saline solution. In group two lavage was
      done with 250 ml of a liquid barrier composed of a combination of high molecular
      weight solution (1% sodium carboxymethylcellulose) as a carrier, non-steroidal
      anti-inflammatory drug (Piroxecam), broad spectrum antibiotic (Cephalosporin),
      anticoagulant (Heparin) and antioxidant (0.5% methylene blue). In group three the
      anastomosis site was covered with a sodium hyalouronate/carboxymethylcellulose
      bioresorbable membrane (Seprafilm). In group four a natural biocompatible
      collagen sheet (VET BIO SIS T) was applied on the anastomosis site. In group five
      the abdominal cavity was lavaged with 250 ml liquid barrier and the anastomosis
      site was covered by either Seprafilm membrane or VET BIO SIS T sheet. At the
      fourteen day after operation, adhesion was assessed by ultrasonography after
      instillation of 1000 ml of physiological saline solution into the abdominal
      cavity. The dogs were sacrificed and an autopsy examination was carried out with
      the attention to the number, density and site of the adhesion formation. The
      results revealed that all the control dogs and some dogs in the treatment groups
      had positive ultrasonographic findings. Transabdominal sonogram clearly showed
      echogenic bands floating in the abdominal cavity and echogenic masses in more
      serious subjects. Necropsy examination showed that all the control dogs had intra
      abdominal adhesions (8 of 8 dogs) and treatment with liquid barrier (4 of 8
      dogs), seprafilm membrane barrier (3 of 8 dogs), VET BIO SIS T sheet barrier (4
      of 8 dogs) and combination of fluid and membrane barrier groups (4 of 8 dogs)
      significantly (p < 0.05) reduced the incidence of adhesion formation. The
      adhesion severity in the four treated groups was significantly (p < 0.05)
      decreased compared with the control group as shown by both ultrasonography and
      necropsy examination scores. In conclusion the suggested hypothesis is more or
      less positive and the combined liquid and membrane barriers might be an effective
      way to decrease intra-abdominal adhesion formation, and the ultrasonography is a
      useful tool to diagnose intra-abdominal adhesion, and their applications might be
      valuable to the clinical settings.

PMID- 15714870
TI  - [Treatment of chronic bovine endometritis and factors for treatment success].
AB  - In a controlled field trial, 178 dairy cows with chronic endometritis and at
      least 21 days in lactation were randomly assigned to four different treatment
      groups: prostaglandin F2alpha intramuscularly (PG, 5 mg dinoprost (5 ml
      Dinolytic), n = 51), intrauterine antibiotics (AB; 400 mg ampicillin + 800
      oxacillin (20 ml Totocillin), n = 49), intrauterine antiseptics (AS; 100 ml 4%
      Lotagen, n = 50); control (C, no initial treatment, n = 28). Before treatment,
      uterine swabs for bacteriologic examination and blood samples for determination
      of serum progesterone concentrations were collected. Two weeks following the
      first treatment, cows were reexamined. In case no clinical cure was diagnosed,
      treatment was repeated and control cows were treated for the first time with one
      of the three treatments mentioned above. The four treatment groups did not differ
      with respect to the clinical cure or reproductive performance. Therefore, factors
      that might have an influence on clinical cure and fertility were evaluated. With
      increasing duration of lactation, the clinical cure after a single treatment
      increased significantly over all treatment groups from 59.5% (treatment before
      day 42 postpartum) to 79.6% (treatment following day 42 postpartum) (P < 0.05).
      Within the PG group, a statistically significantly higher cure rate after a
      single treatment and first service conception rate and a lower pregnancy index
      were obtained when the treatment was performed following day 42 postpartum (P <
      0.05). This was not the case in the other treatment groups. A retarded involution
      of the uterus based on the size had a negative effect on clinical cure over all
      groups (first treatment clinical cure: 68.2% (small uteri) vs 44.4% (large
      uteri); P < 0.05). Within groups, this effect was also detected, but only as a
      trend (P > 0.05). Isolation of Arcanobacterium (A.) pyogenes negatively
      influenced first treatment clinical cure over all treatment groups (79.0% vs
      31.5%) and within treatment groups (P < 0.05). In the AB group, the pregnancy
      index, days open and the interval from first insemination to conception increased
      compared with the other treatment groups, when A. pyogenes was detected.
      Isolation of unspecific bacteria and the presence or absence of a corpus luteum
      only had minor effects over all and within the PG, AS and C group. Within the AB
      group, presence of luteal tissue was connected with a higher pregnancy index and
      increased days open and interval from first insemination to conception (P <
      0.05). A multivariate analysis revealed that the presence of A. pyogenes and no
      initial treatment (control group) had a statistically significant independent and
      negative influence on the first treatment clinical cure. Ill-smelling vaginal
      discharge and no treatment had a negative independent effect on first service
      conception rate. Furthermore, days open were negatively influenced by the
      interval from calving to first examination and the presence of ill-smelling
      vaginal discharge. In conclusion, under the conditions of this field study, it
      seems preferrable to treat chronic endometritis. However, under the condition of
      a herd health program with continuous observation of sick and healthy animals, a
      wait-and-see attitude might also be justified.

PMID- 15714871
TI  - A retrospective description of a highly pathogenic avian influenza A virus
      (H7N1/Carduelis/Germany/72) in a free-living siskin (Carduelis spinus Linnaeus,
      1758) and its accidental transmission to yellow canaries (Serinus canaria
      Linnaeus, 1758).
AB  - A haemagglutinating virus was isolated in summer 1972 from a single free-living
      siskin (Carduelis spinus Linnaeus, 1758) in embryonated chicken eggs. Additional
      cases of morbidity or mortality were not observed in the area were the sick
      siskin was found. The virus was characterized as an avian influenza A virus of
      the subtype H7N1 and designated H7N1/Carduelis/Germany/72. The virus induced
      following experimental inoculation of chicken embryos a high rate mortality (mean
      death time approximately 24 hours), formed plaques in chicken embryo fibroblast
      cultures without addition of trypsin and has an intracerebral pathogenicity index
      (ICPI) of 1.80. Therefore, this virus is considered as a highly pathogenic avian
      influenza A virus. Canaries (Serinus canarius Linnaeus, 1758), that were housed
      in the same room with the siskin were accidentially exposed by contact to the
      sick siskin which resulted in virus transmission followed by conjunctivitis,
      apathy, anorexia and a high rate mortality.

PMID- 15714872
TI  - [The duration of expulsion and the separation of the afterbirth in breeding cows-
      a contribution to the improvement of parturition monitoring].
AB  - The objective of this study was to obtain data on the duration of the expulsion
      and afterbirth stages and on the rate of contractions of the abdominal muscles in
      dams with eutocia (n = 81; heifers: 11; cows: 70). We also looked into the
      questions of whether and at which stage of expulsion there were differences in
      these parameters between cows and heifers as well as purebred Simmental (n = 49)
      and Simmental X Limousin (n = 21). The total period of expulsion (period from
      appearance of the phalanxes in the rima vulvae until the complete expulsion of
      the calf) was 19.7 +/- 2.1 minutes. It took 17.3 +/- 2.3 minutes for the head to
      emerge. Further expulsion required 1.9 +/- 1.7 minutes. At an average of 40.1 +/-
      1.5 minutes, the expulsion stage was longer in heifers than in cows, in which it
      lasted 18 +/- 2.1 minutes (p < 0.01). The differences are due to the time that
      the head took to emerge. While this stage of labor lasted 15.3 +/- 2.3 minutes in
      cows, this interval was clearly longer in heifers, lasting 38.1 +/- 1.5 minutes
      (p < 0.01). No statistically significant difference was observed in the course of
      further expulsion and there were not any differences detected between purebred
      Simmental and Simmental X Limousin. An average of 67.5 +/- 1.6 abdominal
      contractions were required for complete expulsion, 56.5 +/- 1.7 contractions of
      the abdominal muscles were necessary until the head appeared. After 9.3 +/- 1.6
      abdominal presses, the calf had completely emerged. There was a statistically
      significant difference between cows (52.8 +/- 1.7) and heifers (93.3 +/- 1.6)
      until the expulsion of the head (p < 0.01). No breed-specific differences were
      observed. Separation of the afterbirth was observed in 95.0% of the animals up to
      the eighth hour post partum. Retarded separation and retained placenta were
      recorded in 2.5% of the animals in each case. 82.7% of the animals performed
      placentophagy. No placentophagy was observed when the placenta was retarded. No
      differences were detected between heifers and cows and the breeds with regard to
      the separation of the afterbirth and the incidence of placentophagy.

PMID- 15714873
TI  - [The perception of veterinary medicine in the print media].
AB  - Between January 2000 and October 2003, a print media data bank on published
      contributions was screened for the German key words "Tierarzt/Tierarztin" and
      "Veterinar/Veterinarin" (veterinary surgeon) and related items. 267 articles have
      been found. Regarding the contents, the articles were characterised according to
      the content (VPH, surgeons, other), and the cause of the article. Regarding the
      surgeon part, mostly companion animals are dealt with. If it comes to VPH,
      primarily so called scandals such as misuse of therapeuticals or epidemics (BSE,
      FMD) have been reported. In the first instance these articles reflect only a
      temporary interest, and they do not give real insight into the daily work of the
      profession. As a consequence, public intelligence on veterinary medicine may be
      misled by such press articles, possibly generating wrong expectations in young
      people who might start with veterinary medicine. Institutional bodies should
      provide information, which covers the subject in a more realistic way in order to
      prevent a wrong understanding of the profession and to offer the whole scope of
      the public functions of veterinary medicine.

PMID- 15714874
TI  - [Hyperextension of fetlock joints in German Holstein and German Holstein-Limousin
      crossbred calves].
AB  - In two different dairy farms six calves exhibiting bilateral flexion of the
      fetlock joints in front or rear legs were born in 2000 to 2002. Four of the
      affected calves from the same farm were crossbred between German Holstein cows
      with red and white coat colour and a bull of the breed Limousin. The other two
      affected calves born on another farm were purebred German Holsteins with a black
      and white coat colour. The tests for BVD virus antigen and antibodies were
      negative in all affected calves. Three of the calves showed a lower selen and a
      higher glutamate dehydrogenase concentration in the analyses of blood
      metabolites. Two crossbred calves showed a degeneration of the liver with a
      progressive periportal fibrosis in a histological examination. In one calf an
      edema of astrocytes of the central nervous system was seen. The analysis of the
      pedigrees revealed for the four crossbred calves the Limousin bull as common
      ancestor and the mothers of the calves as relatives. For the affected purebred
      German Holstein calves also a sire was identified as a common ancestor. The
      pedigrees support inheritance through a monogenic autosomal recessive locus or
      more recessive gene loci with variable expressivity. However, the analysis could
      not clarify whether different gene loci are responsible for the congenital
      anomalies observed in the calves from the two farms and thus, the observed
      anomalies may be different genetic entities. Obvious environmental reasons were
      not found.

PMID- 15714875
TI  - Gene regulation at-a-distance in E. coli: new insights.
AB  - The number of E. coli genes/operons regulated from sites distant from the gene,
      though limited, steadily increases. The regulation of the ula genes, in charge of
      L-ascorbate utilization, as well as the negative autoregulation of the non
      related lambdaCI and 186CI repressors, for efficient switching of the
      corresponding phages from lysogeny to lysis, are recent examples. The interaction
      between the two GalR dimers, separated by 114 bp, undetectable in vitro, has been
      genetically mapped. lac repressor-operator loops might insulate a gene and its
      expression from the genomic environment. The genes in charge of nitrogen
      assimilation sequentially react to ammonia deprivation, via an increasing
      intracellular NRI concentration. Other sigma54-dependent genes are activated in
      response to various stimuli.

PMID- 15714876
TI  - Hierarchical clustering based upon contextual alignment of proteins: a different
      way to approach phylogeny.
AB  - We perform a computational study using a new approach to the analysis of protein
      sequences. The contextual alignment model, proposed recently by Gambin et al.
      (2002), is based on the assumption that, while constructing an alignment, the
      score of a substitution of one residue by another depends on the surrounding
      residues. The contextual alignment scores calculated in this model were used to
      hierarchical clustering of several protein families from the database of Clusters
      of Orthologous Groups (COG). The clustering has been also constructed based on
      the standard approach. The comparative analysis shows that the contextual model
      results in more consistent clustering trees. The difference, although small, is
      with no exception in favour of the contextual model. The consistency of the
      family of trees is measured by several consensus and agreement methods, as well
      as by the inter-tree distance approach.

PMID- 15714877
TI  - Effects of cadmium and copper on antioxidant capacities, lignification and auxin
      degradation in leaves of pea (Pisum sativum L.) seedlings.
AB  - Twelve-day-old seedlings of pea were treated for four days by 20 and 100 microM
      of Cd(NO3)2 or CuSO4. In leaves, all treatments caused an increase in the
      lipoperoxidation product rate. However, 20 microM of Cu did not affect the
      growth. Moreover, except for 20 microM of Cu, the activity of unspecific
      peroxidases, used as stress marker, was enhanced in cell walls of metal-stressed
      plants. No change in the antioxidant capacities was observed in plants treated
      with 20 microM of metal. At this dose, the Cd-reduced growth could be associated
      to an elevation in the activities of IAA oxidase and of lignifying peroxidases.
      Increase of these latter, in concert with loss in antioxidant capacities, would
      be responsible for the growth diminution after exposure to 100 microM of metal.
      However, the activity of lignifying enzymes was not affected by 100 microM of Cu.
      The contribution of cell fractions to enzymatic responses to stress is
      emphasized.

PMID- 15714878
TI  - [Biochemical changes associated with cadmium and copper stress in germinating pea
      seeds (Pisum sativum L.)].
AB  - Seeds of pea (Pisum sativum L.) were germinated for four days over two sheets of
      filter paper moistened with H2O (control) and 5 mM Cd(NO3)2 or CuSO4 (treated).
      The relationship between heavy-metal stress and breakdown of storage compounds
      was studied. Germination rate and growth of radicle decreased, while the water
      content in stressed seeds remained around the control values. Cotyledons changed
      their biochemical constituents: disorders in the contents of micronutrients (Fe,
      Mn, Zn), free amino acids and soluble sugars were found. Decline of alpha-amylase
      activity as well as acid phosphatase were also observed, whereas beta-amylase and
      alkaline phosphatase ones were not modified by heavy-metal treatments. These
      results suggest that the inhibition of seed germinations after exposure to
      cadmium or copper is not the consequence of starvation in water uptake by seed
      tissues, but may be due to a failure in the reserve mobilization process from
      cotyledons.

PMID- 15714879
TI  - Protein 4.1R expression in normal and dystrophic skeletal muscle.
AB  - 4.1R pre-mRNA alternative splicing results in multiple mRNA and protein isoforms
      that are expressed in virtually all tissues. More specifically, isoforms
      containing the alternative exon 17a, are exclusively expressed in muscle tissues.
      In this report, we show that these isoforms are preferentially present in the
      myoplasm of fast myofibres. 4.1R epitopes are also found at the sarcolemma of
      both slow and fast myofibres in normal muscle. Interestingly, they are absent
      from dystrophin-deficient sarcolemma of DMD muscle, and colocalize with partially
      expressed dystrophin in BMD muscle. We also show that alternative splicing of
      exons 16 and 17a is regulated during muscle differentiation in an asynchronous
      fashion, with an early inclusion of exon 16 in forming myotubes, and a late
      inclusion of exon 17a. Consistently, Western blot analysis led to characterize
      mainly an approximately 96/98-kDa doublet bearing exons 16-17a-encoding peptide,
      exclusively occurring in the differentiated muscle.

PMID- 15714880
TI  - [Factors controlling soil macrofauna spatial pattern in a pure beech and a mixed
      beech-hornbeam forest].
AB  - The soil macrofauna of a pure beech (PS) and a mixed beech-hornbeam (MS) stand
      was recorded using a sample design spatially explicit at stand level. Humic
      epipedon morphological and chemical properties, relative irradiance, soil bulk
      density, and the specific composition of the litter in MS were also investigated.
      The taxonomic diversity is nearly similar on both sites, but the average by
      sample is greater under PS. The main factors controlling soil macrofauna spatial
      variability were: litter quality under MS and humus form activity under PS. These
      results suggest a distal control (i.e. external to humic epipedon) of macrofauna
      spatial variability when the litter quality is variable and a proximal control
      (i.e. internal to humic epipedon) when it is uniform at the spatial scale of the
      study.

PMID- 15714881
TI  - Underwater acoustic positioning systems as tool for Posidonia oceanica beds
      survey.
AB  - The study of the dynamics of Posidonia oceanica beds, and more particularly, the
      position of their lower limit, are usually carried out by the installation and
      monitoring of markers set on the sea bottom. Acoustic telemetry could constitute
      an interesting alternative solution to the marking of the lower limit seagrass
      beds. In order to test the potentialities of this system, an experiment was
      conducted in the Natural Marine Reserve of Cerbere-Banyuls (eastern Pyrenees,
      France). The possibility of very precise mapping offers many potentialities with
      regards to the work of monitoring networks in the marine environment (species and
      assemblages of importance), but also in the monitoring of competition dynamics
      between the species.

PMID- 15714882
TI  - Pollen waste and unrelated traits in a fig-fig wasp symbiosis: a new behaviour
      suggesting a host shift.
AB  - In a fig-fig wasp symbiosis, we have discovered that male fig pollinators
      (Alfonsiella fimbriata Waterston) bite into the dehiscent anthers of Ficus
      natalensis leprieuri Miq., thus scattering the pollen grains throughout the
      syconium. Female pollinators are the only ones to transfer pollen to conspecific
      trees, and collect pollen actively from the anthers only. Thus, this male
      behaviour appears to be antagonistic to the pollination process. We compare
      different wasp pollinating behaviours between fig species exhibiting dehiscent
      and non-dehiscent anthers and conclude that this male behaviour is new and not
      required with spontaneously dehiscent anthers. These findings could suggest a
      host shift of Alfonsiella fimbriata.

PMID- 15714883
TI  - [Maternal inheritance in a subsocial spider: web for collective prey capturing of
      the young].
AB  - Construction of a safe refuge is the first step toward the evolution of social
      organization in spiders. In the case of the subsocial spider Amaurobius Jerox
      (Araneae, Amaurobiidae), the young remain in the natal nest after consuming their
      mother's body (matriphagy). The benefit that the young could obtain from the
      maternal web was investigated in their collective prey capture. The results
      demonstrated the adaptive value of the maternal web. The prey capturing activity
      was more effective when the young were allowed to stay on the maternal web than
      when they used the web constructed by themselves. Maternal web may also provide a
      better transmission of information on prey state and clutch mates' activities,
      because more spiderlings were recruited to contact and hold the prey in a shorter
      period of time than when they were on a spiderling-constructed web. The young's
      inheritance of the maternal nest is probably one of the crucial ways in which the
      mother influences the post-maternal social period of the young.

PMID- 15714884
TI  - Inter-individual variability during morning choruses in Japanese quail males
      (Coturnix coturnix japonica).
AB  - We compared the organization of dawn choruses in five groups of Japanese quail,
      Coturnix coturnix japonica, males (four groups of kin-related males and one group
      of unrelated males). We documented the structure of chorus groups: one male sang
      much more than the others during the dawn peak in four of the five groups, and
      this regardless of the number of males in the group. The dominant singers were
      then removed from two similar-sized groups, one of kin-related (K3) and the other
      of unrelated (NK) males. The quantity of song emitted by the remaining NK males
      was modified, but not that emitted by the K3 males.

PMID- 15714885
TI  - [Ventricular extrasystoles].
AB  - Ventricular extrasystoles result from premature excitation of the heart from a
      site beyond the bifurcation of the bundle of His, at the level of the conductive
      tissue or myocardial cells. In practice they represent a daily problem for
      cardiologists due to their frequent occurrence. They can be detected in
      symptomatic patients and also in asymptomatic subjects, for example during
      routine health checks. It is therefore important to distinguish benign
      ventricular extrasystoles from those which are potentially serious, so that a
      useless or even dangerous treatment is not undertaken and severe anxiety is not
      caused in patients who have become 'medicalised'. The decision about treatment is
      only made following electrocardiographic and echographic clinical investigation,
      with the presence of cardiopathy being one of the major deciding factors.

PMID- 15714886
TI  - [The electrocardiogram in ventricular tachycardias].
AB  - The electrocardiogram, as much as the clinical examination, is a basic tool for
      the cardiologist. Technological advances have led to a certain lack of interest
      in learning to read the electrocardiogram, for which close analysis can allow
      precise diagnosis, notably in the field of cardiac rhythm disorders. This article
      concerns the electrocardiogram in ventricular tachycardias with two themes:
      differential diagnosis of wide QRS complex tachycardias and recognition of the
      site of origin of a ventricular tachycardia. "Fine" analysis of the
      electrocardiogram is not an intellectual "game". Actually, careful analysis of
      the 12 lead ECG allows exact and rapid diagnosis in a large majority of cases,
      distinguishing a ventricular tachycardia from a supraventricular tachycardia with
      conduction defect; the appropriate management can be selected without delay. At
      the same time, close reading of the electrocardiogram also allows the site of
      origin of a ventricular tachycardia to be recognised. Combining this information
      with elements of the patient's record can allow the arrhythmia to be related to a
      known pathology or to prompt a targeted aetiological investigation.

PMID- 15714887
TI  - [Conduction defects and arrhythmias in peripheral myopathies].
AB  - The association between peripheral myopathies and cardiac complications is well
      established. However, until recently, the clinical and genetic variability of
      these pathologies limited our ability to recognise individual risk of
      complications, particularly in the more rare pathologies. Advances have been made
      in the understanding of the progression, in the physiopathology of molecular
      deficits and cardiac complications of the different types of muscular dystrophy.
      This has partially helped to identify the risk of cardiac complications. The
      commonest condition, Steinert's disease, is associated with a high incidence of
      atrioventricular block and atrial arrhythmias. Prophylactic implantation of a
      dual chamber pacemaker with diagnostic functions may be envisaged when the HV
      interval is greater than 70 ms, on endocavitary electrophysiological
      investigations. In other patients, follow-up by standard ECG and/or amplified
      averaged ECG and Holter monitoring is essential. The natural history of Duchenne
      and Becker muscular dystrophies and the Emery Dreifuss dystrophy have been better
      described in the last few years. Recommendations have been proposed for the
      cardiological follow-up of these patients. Empiric recommendations of the same
      type have been proposed for patients with shoulder and girdle myopathies and
      propositions for their management have also been made, the pertinence of which is
      still being evaluated. Our understanding of the incidence, the type, the
      physiopathology and molecular biology of the various peripheral myopathies and
      their cardiac complications has advanced considerably in recent years. This has
      led to the elaboration of new recommendations for diagnostic and therapeutic
      strategies in these patients.

PMID- 15714888
TI  - [The electrocardiogram of atrioventricular blocks].
AB  - Atrioventricular block (AVB) is defined as delay or absence of transmission of
      one or more atrial excitations to the ventricle. Physiological functional block
      protects the ventricle against very rapid atrial rhythms. Organic blocks may be
      transient, due to an acute regressive condition, or chronic, in which case they
      fall into two groups--permanent blocks or paroxysmal and generally rate-dependant
      blocks. The blocks are classified in three categories according to whether the
      atrial activation is delayed, conducted intermittently or not at all. The site of
      AVB may be determined by His bundle recordings but it may also be deduced from
      the surface ECG recording. Fundamental studies have questioned the reality of
      Rosenbaum's phase 3 and 4 blocks and suggest abnormalities of excitability in
      pathological zones.

PMID- 15714889
TI  - [The choice of pacing sites: should we change our practice?].
AB  - For the past 45 years the sites used for elective pacing have been the apex of
      the right ventricle and the right atrium. Although the initial objective of
      pacing was the "simple" correction of a conduction disorder, a more recent
      evolution has been to achieve a favourable haemodynamic effect, considering left
      ventricular filling and synchronisation of ventricular contraction as essential.
      Demonstration of the benefit in terms of survival brought about by pacing in
      atrioventricular block has not required large trials. However, it is possible
      that this improvement in morbidity and mortality is in part offset by the altered
      haemodynamics due to pacing at the right ventricular apex. At the atrial level,
      the prevention of AF is the holy grail of atrial pacing, but is far from being
      attained, perhaps because the physiopathological bases are not clear and have not
      really been demonstrated, casting doubt on the final objective. The choice of
      pacing site is essential in this context, as much in the atrium as in the
      ventricle. The current problem regarding this choice is the same as for all
      medical treatment, where the risk/benefit ratio is evaluated: if the usual sites
      are potentially deleterious, is it possible to continue using them or is it
      necessary to change implantation practices, and what level of proof is needed?

PMID- 15714890
TI  - [Sinus-like tachycardias].
AB  - Various tachycardias presenting with positive P waves in the standard leads are
      described in this article. Sinus tachycardia may occur as a normal adaptation
      reaction to the environment or in the setting of autonomic dysregulation. It may
      also be mimicked by various arrhythmias which share the earliest depolarisation
      in the sinus node area. The authors expose a review of these mechanisms.

PMID- 15714891
TI  - [Pharmacological treatment of atrial fibrillation].
AB  - Although anticoagulant treatment of atrial fibrillation is now well codified, the
      medical treatment of the fibrillation remains controversial. Two types of
      medication can be proposed: drugs to slow the rhythm (digitalis, betablockers and
      calcium inhibitors) and anti-arrhythmic mainly Class I or Class III drugs. Some
      doubt was raised in the 1990's about the pertinence of antiarrhythmic therapy and
      four recent trials (AFFIRM, RACE, PIAF and STAF) compared the two attitudes of
      "rhythm control" or "rate control" in atrial fibrillation. The four trials all
      showed that the results of these two options were equivalent with respect to the
      therapeutic objectives: reduction of mortality, thromboembolic or haemodynamic
      risk, and regression of symptoms and improvement of the quality of life. However,
      these trials have not closed the debate on these two therapeutic attitudes. In
      fact, analysis shows that the comparison was biased because anticoagulant
      treatment was inadequate and, though the treatment for rate control was
      appropriate, the antiarrhythmic treatment was far from being satisfactory and
      effective. Moreover, many patients in the "rhythm control" group were in atrial
      fibrillation whereas a certain number of patients in the "rate control" group
      were, in fact, in sinus rhythm throughout the study period. In addition, the
      comparison was incomplete because it did not include two other particularly
      common populations in clinical practice: multi-relapsing paroxysmal atrial
      fibrillation in healthy hearts and atrial fibrillation associated with severe
      left ventricular dysfunction, patients with cardiac failure. Until the results of
      trials currently under way (AF-CHF) become available, the authors discuss the use
      of drugs for rate control and antiarrhythmic therapy in everyday practice.

PMID- 15714892
TI  - Cortex forum on the concept of general intelligence in neuropsychology.

PMID- 15714893
TI  - The hidden structure of neuropsychology: text mining of the journal Cortex: 1991-
      2001.
AB  - BACKGROUND: The stated mission of Cortex is "the study of the inter-relations of
      the nervous system and behavior, particularly as these are reflected in the
      effects of brain lesions on cognitive functions." The purpose of this paper is to
      explore the relationship between the stated mission and the executed mission as
      reflected by the characteristics of papers published in Cortex. In addition, we
      examine whether the results and conclusions of an analysis of this kind are
      affected by the level of description of the published papers. OBJECTIVES: A)
      Identify characteristics of contributors to Cortex; B) Identify characteristics
      of those who cite Cortex; C) Identify recurring themes; D) Identify the
      relationships among the recurring themes; E) Compare recurring themes and
      determine their relationships to the mission of Cortex; F) Identify the
      sensitivity of these results to the level of description of the Cortex papers
      used as the source database. G) Compare Cortex characteristics with those of
      Neuropsychologia, another Europe-based international neuropsychology journal.
      METHODS: Text mining (extraction of useful information from text) was used to
      generate the characteristics of the journal Cortex. Bibliometrics provided the
      Cortex contributor infrastructure (author/ organization/ country/ citation
      distributions), and computational linguistics identified the recurring technical
      themes and their inter-relationships. Citation mining (the integration of
      citation bibliometrics and text mining) was used to profile the research user
      community. Four levels of published article description were compared for the
      analysis: Full Text, Abstract, Title, Keywords. RESULTS AND CONCLUSIONS: Highly
      cited documents were compared among Cortex, Neuropsychologia, and Brain, and a
      number of interesting parametric trends were observed. The characteristics of the
      papers that cite Cortex papers were examined, and some interesting insights were
      generated. Finally, the document clustering taxonomy showed that papers in Cortex
      can be reasonably divided into four categories (papers in each category in
      parenthesis): Semantic Memory (151); Handedness (145); Amnesia (119); and Neglect
      (66). It is concluded that Cortex needs to take steps to attract a more diverse
      group of contributors outside its continental Western European base if it wishes
      to capture a greater share of seminal neuropsychology papers. Further
      investigation of the critical citation differences reported in the paper is
      recommended.

PMID- 15714894
TI  - Staring in the eye of auditory neglect: comments on 'gaze direction modulates
      auditory spatial deficits in stroke patients with neglect'.
AB  - In the current issue of Cortex, Pavani and colleagues show that directing gaze
      toward the contralesional hemifield significantly diminishes the auditory
      deficits associated with unilateral neglect. The authors suggest that this
      beneficial effect of gaze direction may arise due to the recruitment of
      crossmodal attentional links between audition and vision. A complementary
      interpretation of these findings is that directing gaze toward neglected sound
      sources encourages the recoding of auditory spatial location in a relatively
      preserved frame of reference, and that it is through this coordinate
      transformation process that awareness of auditory stimuli may be regained.
      Rehabilitation strategies aimed at recoding stimuli within relatively preserved
      reference frames may be a useful step forward in managing unilateral neglect.

PMID- 15714895
TI  - A pet study of visual and semantic knowledge about objects.
AB  - The distinctiveness of temporal lobe regions activated during the retrieval of
      knowledge regarding structural, colour and associative (encyclopaedic) aspects of
      familiar objects was investigated using PET. These three types of knowledge were
      contrasted using well matched tasks requiring the detection, in a series of
      coloured-in line drawings, of occasional anomalous objects (in the three
      conditions: structurally incorrect chimeras composed of parts of real objects;
      inappropriately coloured objects; familiar objects that do not exist in the
      modern world). Relative to a resting baseline condition, all semantic retrieval
      tasks yielded extensive bilateral activations in occipital and temporal areas,
      extending anteriorly on the ventral surface of the brain, plus an area in the
      right superior parietal lobe. In direct semantic-task comparisons focussing on
      the temporal lobe: (i) structural relative to associative decisions activated the
      right posterior middle/inferior temporal gyrus; (ii) colour decisions relative to
      structural judgements were associated with a region in the right superior
      temporal gyrus; (iii) the associative decision task selectively activated the
      left anterior middle/superior temporal gyrus and temporal pole relative to both
      object structure and colour, and also the homologous right temporal pole relative
      to colour only. These results indicate that each type of stored knowledge
      involves at least partially distinct cortical areas, and suggest that both
      anterior/posterior and left/right temporal regions have specialised roles.

PMID- 15714896
TI  - Allocentric and egocentric spatial impairments in a case of topographical
      disorientation.
AB  - We describe a patient with a topographical disorientation after a stroke of the
      right mediotemporooccipital lobe including the parahippocampal cortex (PHC).
      Clinical observations and neuropsychological testing reveal an impairment of
      allocentric spatial representations as well as impairments of visuospatial
      learning and memory. These findings are in accordance with the well-known
      function of the PHC in topographical disorientation. As a new finding, results
      from oculomotor tasks show additional impairments of the egocentric spatial
      coordinate frame suggesting that in topographical disorientation due to a lesion
      of the right mediotemporooccipital lobe not only allocentric but also egocentric
      visuospatial functions are disturbed.

PMID- 15714898
TI  - Hemispheric specialization for language in children with different types of
      specific language impairment.
AB  - The aim of the study was to investigate whether children with Specific Language
      Impairment (SLI) show reduced left hemisphere specialization for language and, if
      so, whether it is associated with a deficit in phonological encoding and a
      specific type of SLI (Mixed Receptive-Expressive, Expressive, Phonological). We
      adopted two dichotic listening paradigms, which differed in the phonological
      similarity of the presented words (Fused and Non-Fused dichotic words tests), as
      well as a phonological working memory test. Participants included 34 pre-school
      and school age children affected by SLI. On the dichotic tests, as a group the
      children with SLI showed a reduced pattern of left hemisphere specialization for
      language compared to age-matched normal children, with significant differences
      only in the Fused condition. However, the pattern of hemispheric specialization
      varied depending on the type of SLI, with reduced left hemisphere specialization
      in the Expressive type and, to a lesser extent, in the Phonological type of SLI,
      but not in the Receptive-Expressive type. The three subgroups also differed in
      phonological processing abilities and the incidence of a positive family history
      for language disorders: the Receptive-Expressive group performed worse on the
      working memory and dichotic tests and the Expressive and Phonological groups
      presented high frequency for familial language disorder. These results suggest
      that different subtypes of SLI are not different manifestations of the same
      underlying disorder, but represent pathological conditions that have distinct
      markers both at the behavioral and neurofunctional level.

PMID- 15714897
TI  - Visuospatial and numerical cognitive deficits in children with chromosome 22q11.2
      deletion syndrome.
AB  - This article presents some of the earliest evidence of visuospatial and numerical
      cognitive deficits in children with the chromosome 22q11.2 deletion syndrome; a
      common but ill-understood genetic disorder resulting in medical complications,
      cognitive impairment, and brain morphologic changes. Relative to a group of
      typically developing controls, deleted children performed more poorly on tests of
      visual attentional orienting, visual enumeration and relative numerical magnitude
      judgment. Results showed that performance deficits in children with the deletion
      could not be explained by a global deficit in psychomotor speed. Instead, our
      findings are supportive of the hypothesis that visuospatial and numerical
      deficits in children with the chromosome 22q11.2 deletion are due, at least in
      part, to posterior parietal dysfunction.

PMID- 15714899
TI  - Love is... an abstract word: the influence of lexical semantics on verbal short
      term memory in Williams syndrome.
AB  - It has been claimed that verbal short-term memory in Williams syndrome is
      characterised by an over-use of phonological coding alongside a reduced
      contribution of lexical semantics. We critically examine this hypothesis and
      present results from a memory span task comparing performance on concrete and
      abstract words, together with a replication of a span task using phonologically
      similar and phonologically dissimilar words. Fourteen participants with Williams
      syndrome were individually matched to two groups of typically developing
      children. The first control group was matched on digit span and the second on
      vocabulary level. Significant effects were found for both the semantic and the
      phonological variables in the WS group as well as in the control groups, with no
      interaction between experimental variable and group in either experiment. The
      results demonstrate that, despite claims to the contrary, children and adults
      with WS are able to access and make use of lexical semantics in a verbal short
      term memory task in a manner comparable to typically developing individuals.

PMID- 15714900
TI  - Gaze direction modulates auditory spatial deficits in stroke patients with
      neglect.
AB  - We investigated the effects of eye position on auditory spatial deficits in four
      patients with left neglect and right-hemisphere damage, using three blocked gaze
      directions (35 degrees to the right, central, or 35 degrees to the left), while
      preventing any head-movement to ensure that initial auditory inputs remained
      constant regardless of eye-in-orbit position. The auditory task required speeded
      discrimination of sound elevation, with patients moving a central lever up or
      down according to the vertical position of a peripheral target sound, regardless
      of its side (left or right). Replicating previous auditory research, the
      patients' vertical discrimination performance was worse for auditory targets on
      the contralesional (left) versus the ipsilesional side, indicating neglect
      related auditory deficits on this task. Critically, while this worse performance
      for left than right auditory targets was present (for both reaction times and
      errors) when gaze was directed centrally or rightwards, it was considerably
      reduced when gaze was directed leftwards. These results demonstrate that lateral
      gaze-direction can modulate neglect-related auditory spatial deficits, even
      though eye-position did not alter the initial auditory inputs. This outcome may
      relate to audio-visual links in spatial orienting and potentially some
      retinocentric influences on perceived sound location, although the latter alone
      could not explain all our results. Such findings might involve multisensory brain
      structures in which responses to sounds are modulated by eye-in-orbit position.

PMID- 15714901
TI  - Processing of affective stimuli in alcoholism.
AB  - Investigations of neuropsychological functioning in alcoholism have revealed
      executive and memory deficits which have been interpreted in the light of the
      "frontal lobe hypothesis" which asserts that the frontal lobes are particularly
      vulnerable to the toxic effects of alcohol. Inspite of the known involvement of
      the orbitofrontal cortex in the processing of affective stimuli, only few studies
      concerning affective processing in alcoholism have been conducted so far.
      Alcoholics and healthy controls were compared by using a comprehensive
      neuropsychological test battery which included the measurement of facial affect
      as well as affective prosody perception. Analysis revealed impairments of
      alcoholics with respect to naming prosody with incongruent semantic content and
      matching affective prosody to facial expression. Alcoholics showed deficits of
      affective prosody processing which became evident in ambiguous situations in
      which no additional cues could be used simultaneously for the interpretation of
      emotional prosody. These deficits could contribute to interpersonal problem
      solving and should thus be considered in the therapy of alcoholism.

PMID- 15714902
TI  - Drawing from childhood experience: constructional apraxia and the production of
      oblique lines.
AB  - We report the performance of two patients (ECR and RA) with constructional
      apraxia on a drawing task previously used to test the development of planning
      abilities in children. Patients and controls were required to produce both
      oblique and horizontal/vertical lines that formed a right angle. Planning demands
      were manipulated across conditions by providing additional spatial information to
      constrain the drawing. Both patients produced drawings that were less accurate
      than controls. In addition, ECR was particularly poor at producing oblique lines
      compared to both RA and controls, even under conditions with minimal planning
      demands. This pattern of performance is qualitatively similar to that of children
      under eight years (see Broderick and Laszlo, 1988). Taken together these results
      provide further evidence that constructional apraxia is not a unitary disorder
      (with differential performance between patients) and that those differences are
      not necessarily related to laterality of damage (as both patients had right
      hemisphere lesions). We argue for a more quantitative approach to the study of
      drawing abilities in neuropsychological testing in order to facilitate a finer
      grained analysis of the disorder and of comparison between patients.

PMID- 15714903
TI  - Saccade-contingent spatial and temporal errors are absent for saccadic head
      movements.
AB  - Psychophysical studies extending over a thirty-year period have repeatedly
      demonstrated that visual stimuli presented close to the onset of a saccadic eye
      movement are mislocalised both spatially and temporally. When post-saccadic
      visual references are available, this spatial distortion is best characterised by
      a compression of visual space toward the target of the saccadic eye movement. An
      important but unresolved issue, concerns the specificity of saccade-dependent
      visual mislocalisation phenomena. We investigated this by examining whether
      saccade-dependent spatial and temporal mislocalisation are observed in an
      individual (A.I.) who cannot make any form of eye movement (opthalamoplegia), but
      compensates when reading or scanning visual scenes by making saccadic head
      movements. We demonstrate that saccade-dependent spatial and temporal
      mislocalisation are absent in subject A.I. and suggest that spatiotemporal
      mislocalisation may be specific to rapid forms of movement, such as ocular
      saccades, that necessitate predictive re-mapping to maintain space constancy.

PMID- 15714904
TI  - Frontal lobe function and general intelligence: why it matters.

PMID- 15714905
TI  - Duncan's spearman's G--does it have a clinical application?

PMID- 15714906
TI  - Executive function or G? Hmmmmm...

PMID- 15714907
TI  - Intelligence and executive control: evidence from aging and bilingualism.

PMID- 15714908
TI  - The principles of cognition and the abilities of man: a natural collaboration.

PMID- 15714909
TI  - The cortical substrate of general intelligence.

PMID- 15714910
TI  - Psychometric G and mental chronometry.

PMID- 15714911
TI  - Difficult questions about g.

PMID- 15714912
TI  - Uncertainty about the biology of intelligence: a role for a marker task.

PMID- 15714913
TI  - Both specific functions and general ability can be useful: but it depends what
      type of research question you ask.

PMID- 15714914
TI  - Frontal brain changes and cognitive performance in old age.

PMID- 15714915
TI  - G is about variance not contents.

PMID- 15714916
TI  - The importance of converging operations in the study of human intelligence.

PMID- 15714917
TI  - Our paper on "Visual orientation impairment in the three dimensions of space. An
      anatomical case".

PMID- 15714918
TI  - Egon Weigl and the concept of inner speech.

PMID- 15714919
TI  - On the use of neuropsychology to diagnose brain damage and study brain-behavior
      relationships: a comment on Luria.

PMID- 15714920
TI  - Anosognosia and body representations forty years later.

PMID- 15714921
TI  - The history of neuropsychology according to Norman Geschwind: continuity and
      discontinuity in the development of science.

PMID- 15714922
TI  - Radiation-induced cell death and dendritic cells: potential for cancer
      immunotherapy?
AB  - Dendritic cells are key orchestrators of the immune system. There is considerable
      interest in their use for treating cancer. Whether they initiate an effective
      cytotoxic response against antigen-bearing cells, or produce tolerance, depends
      on the context in which those antigens are presented. Ionising radiation, and the
      cell death it causes, has several properties that may facilitate such an
      effective response. A range of in-vitro and in-vivo data supports this, although
      potential problems exist that may require concurrent strategies.

PMID- 15714923
TI  - Recommendations for influenza and pneumococcal vaccinations in people receiving
      chemotherapy.
AB  - There is some uncertainty among oncologists about the safety and efficacy of
      immunising people undergoing chemotherapy against influenza and Streptococcus
      pneumoniae. This paper aims to summarise current information about this subject
      and provide recommendations for immunising this patient group.

PMID- 15714924
TI  - Reduction of radiotherapy-induced late complications in early breast cancer: the
      role of intensity-modulated radiation therapy and partial breast irradiation.
      Part I--normal tissue complications.
AB  - Radiotherapy after conservation surgery has been proven to decrease local relapse
      and death from breast cancer, and is now firmly established in the management of
      early breast carcinoma. Currently, the challenge is to minimise the morbidity
      caused by this treatment without losing its efficacy. This review will be divided
      into two parts, with Part I focusing on the radiation factors contributing to
      late normal tissue complications after radiotherapy for early breast cancer.
      Three major normal tissue side-effects will be discussed: cosmetic outcome,
      cardiac complications and pulmonary side-effects.

PMID- 15714925
TI  - Assessing breast cosmesis after radiotherapy: what do we want to measure?

PMID- 15714926
TI  - Improving the accuracy of a photographic assessment system for breast cosmesis.
AB  - AIMS: To determine how the accuracy of a photographic system for cosmetic
      assessment of the breast after conserving treatment can be maximised. MATERIALS
      AND METHODS: Photographs of 40 women undergoing breast-conserving treatment for
      breast cancer were taken. Upward and lateral retraction was measured using a
      digitiser to enter the locations of reference marks on the photographs into a
      computer programme. In the readings produced, reduction in three potential
      sources of variation was considered by determining how few repeated photographs
      or measures were necessary to achieve an estimate within +/-2 mm of a mean value
      obtained from a large series. These included variation between assessments of the
      same photograph, between different photographs of the same patient and between
      different observers. We also sought to determine whether the attachment of white
      nipple markers (WNM) at the time of photography would reduce variation. RESULTS:
      A minimum of five readings was required from each photograph in order to obtain a
      result that was stable (defined as within 1 mm of that achieved by 20 readings).
      Using similar criteria, we found that at least four photographs of each patient
      were required, and that each should be assessed by at least four observers. The
      addition of WNM reduced the standard deviations by 36-45%. CONCLUSION: The use of
      WNM, which is simple, quick and cheap, is effective in reducing variation and can
      be recommended for use in clinical trials where overhead costs need to be
      contained.

PMID- 15714927
TI  - Matching supraclavicular fields to the extent of axillary surgery in women
      prescribed radiotherapy for early stage carcinoma of the breast.
AB  - AIMS: To determine (1) if the lower border of a standard anterior radiotherapy
      field to the supraclavicular fossa matches the upper limit of level II/III
      axillary dissection; and (2) whether standard lung blocks in patients prescribed
      axillary radiotherapy shield target axillary tissue in women with breast cancer.
      MATERIALS AND METHODS: Between 1999 and 2001, 30 women with breast cancer
      undergoing level II/III axillary dissection had titanium clips placed to define
      the upper and medial limits of surgery. At radiotherapy planning, a
      supraclavicular fossa field similar to that described in the UK START trial
      protocol was simulated, with head twist applied to position the inferior field
      border (50% isodose) 1 cm below and parallel to the lower border of the clavicle.
      The field position was recorded on X-ray film. The location of the most superior
      axillary clip was measured in relation to this inferior field border on the X-ray
      film. The location of the most medial clip was measured in relation to the
      lung/chest wall interface. RESULTS: The median distance between the most superior
      clip and the inferior border of the supraclavicular field was 3.6 cm (0.8-6.9
      cm), representing significant underlap in all cases. In addition, five out of 30
      (17%) patients had surgical clips over 2.0 cm medial to the lung/chest wall
      interface, suggesting that medial lymph nodes in an undissected axilla would be
      shielded by standard lung blocks in patients prescribed axillary radiotherapy.
      CONCLUSION: Current standard radiation fields to the supraclavicular fossa, as
      applied in this study, leave apical axillary lymph nodes untreated in a high
      proportion of patients. Standard lung shielding, as applied in this study to
      patients simulated for axillary radiotherapy, protect medial axillary lymph nodes
      in a few patients. A change in practice is recommended.

PMID- 15714928
TI  - Sequential pulmonary effects of radiotherapy detected by functional and
      radiological end points in women with breast cancer.
AB  - AIMS: To determine the pulmonary effects of locoregional irradiation on clinical
      and sub-clinical radiographic and functional end points in women with breast
      cancer, and whether the course of these end points is affected by laterality.
      MATERIALS AND METHODS: Twenty patients (10 irradiated on the left side and 10
      irradiated on the right side) were prospectively evaluated for changes in
      pulmonary function tests, Tc-99m DTPA (diethylenetriamine pentaacetic acid) lung
      clearance scintigraphy and high-resolution computed tomography (HRCT) at 6, 16
      and 52 weeks after radiotherapy. Tc-99m DTPA clearance, expressed as the
      biological half-time, T(1/2), was computed from the time-activity curves for 10
      min for each lung. The irradiated lung volume was calculated for each patient.
      RESULTS: The mean irradiated lung volume was 6.4% +/- 2 (range 3-11%) for the
      entire population. In the whole study population, two (10%) patients, who were
      irradiated on the left side, had mild symptomatic radiation pneumonitis in the
      follow-up period. There was a statistically significant gradual reduction in all
      pulmonary function test values during the follow-up period. For patients
      irradiated on the left side, Tc-99m DTPA clearance T(1/2) values were
      statistically significantly decreased during the follow-up period (P = 0.03), but
      the decrease was not statistically significant for patients irradiated on the
      right side (P = 0.62). Tc-99m DTPA clearance T(1/2) values were statistically
      significantly decreased in the irradiated lung compared with the opposite lung,
      and no improvement was seen at week 52 after radiotherapy. The number of patients
      with changes on HRCT scans increased after radiotherapy, reaching a maximum at 16
      weeks, when 80% of patients had changes. There was subsequent partial recovery 52
      weeks after radiotherapy. CONCLUSION: Locoregional irradiation for breast cancer
      may cause sub-clinical irreversible impairment of radiological and functional
      pulmonary parameters. The increase in clearance rate of Tc-99m DTPA may be more
      prominent for patients with left-sided breast cancer.

PMID- 15714929
TI  - Long-term results of a randomised trial of involved field radiotherapy vs
      extended field radiotherapy in stage I and II Hodgkin lymphoma.
AB  - Involved field (IF) radiation was compared with extended field (EF) radiation in
      Hodgkin lymphoma (HL) to ascertain whether reduced radiation fields would reduce
      the late sequelae of radiation without compromising disease control and survival.
      A total of 603 patients with stage I or II HL were entered into this trial;
      laparotomy was carried out in 380 (63%) patients. Stage I or IIA disease patients
      were randomised to receive IF or EF comprising a mantle or inverted Y fields
      alone. Stage I and IIB patients were randomised between mantle or inverted Y
      fields and total nodal irradiation (TNI). The dose was 35 Gy to uninvolved sites
      and 40 Gy to involved sites. The median followup of surviving patients was 25.2
      years with only 3.3% lost to follow-up. The treatment failure rate at 25 years in
      stage IA and IIA was 44% after EF and 54% after IF (P = 0.01); in stage I and IIB
      this was 80% (EF) and 82% (TNI) at 25 years. No difference in overall survival
      between the randomised groups was seen. The incidence of second malignancies was
      21% after IF and 20% after EF with a slight excess of lung cancer in the EF
      group. No significant differences in the causes of death between the randomised
      arms have emerged. In conclusion, IF radiotherapy for stage I and IIA HL results
      in a 11% greater risk of relapse compared with EF but has no effect on overall
      survival, risk of second malignancy or cause of death at 25 years.

PMID- 15714930
TI  - Radiotherapy and Marfan syndrome: a report of two cases.
AB  - Marfan syndrome (MFS) is a heritable disorder of the connective tissue which has
      been linked to mutations in the FBN (fibrillin-1) gene. Murine knockouts of the
      FBN gene show increased interstitial fibrosis and TGF-beta (tumor growth factor
      beta) gene activation. Abnormal TGF-beta expression has previously been linked to
      radiation-induced fibrosis, suggesting a possible link between MFS and increased
      late effects following radiotherapy. Herein we report two cases in which MFS
      patients treated with radical radiotherapy without undue acute or late
      radiotherapy toxicity suggesting that radiotherapy should not be withheld from
      MFS patients. MFS patients may provide a unique clinico-translational setting to
      test associations between FBN mutations, TGF-beta activation and the risk of
      tissue fibrosis.

PMID- 15714931
TI  - Gorham's syndrome.

PMID- 15714932
TI  - Palliative radiotherapy for non-small-cell lung cancer: which dose?

PMID- 15714933
TI  - Symptom control and quality of life in people with lung cancer: a randomised
      trial of two palliative radiotherapy fractionation schedules.
AB  - AIMS: To determine whether palliation of chest symptoms from a 10 Gy single
      fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen
      2). MATERIALS AND METHODS: Patients with cytologically proven, symptomatic lung
      cancer not amenable to curative therapy, with performance status 0-3, were
      randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction.
      Local symptoms were scored on a physician-assessed, five-point categorical scale
      and summed to produce a total symptom score (TSS). This, performance status,
      Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index
      were noted before treatment, at 1 month after treatment and every 2 months
      thereafter. Palliation was defined as an improvement of one point or more in the
      categorical scale. Equivalence was defined as less than 20% difference in the
      number achieving an improvement in the TSS. RESULTS: We randomised 149 patients
      and analysed 74 in each arm. According to the design criteria, palliation was
      equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1,
      and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence
      interval [CI] 3-28) in the proportion improving between the two regimens. A
      complete resolution of all symptoms was achieved in three (5%) on regimen 1, and
      in 14 (23%) patients on regimen 2 (P < 0.001), a difference in the proportion
      between the two regimens of 21% (95% CI 10-33). A significantly higher proportion
      of patients experienced palliation and complete resolution of chest pain and
      dyspnoea with regimen 2. No differences were observed in toxicity. The median
      survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197).
      CONCLUSIONS: Although this trial met the pre-determined criteria for equivalence
      between the two palliative regimens, significantly more patients achieved
      complete resolution of symptoms and palliation of chest pain and dyspnoea with
      the fractionated regimen.

PMID- 15714934
TI  - Successful treatment of thymoma-associated erythroid hypoplasia and
      thrombocytopenia with paclitaxel.

PMID- 15714935
TI  - Long-term outcomes and morbidity after I125 brachytherapy for localised prostate
      cancer: an early UK series.

PMID- 15714936
TI  - Human immunodeficiency virus-associated Hodgkin's disease of the anal canal.

PMID- 15714937
TI  - Primary peritoneal carcinoma with acute renal failure: successful treatment with
      chemotherapy.

PMID- 15714938
TI  - Right ventricular outflow tract obstruction secondary to myocardial metastases
      from colorectal cancer.

PMID- 15714939
TI  - Femtosecond dynamics of transition processes in reaction centers of Rhodobacter
      sphaeroides.

PMID- 15714940
TI  - Structural characteristics of the third open reading frame of the retrotransposon
      gtwin in different strains of Drosophila melanogaster.

PMID- 15714941
TI  - The informational approach to the structure-function relationship in biological
      macromolecules.

PMID- 15714942
TI  - Different sensitivity of squid cholinesterases to irreversible organophosphorous
      inhibitors may be used as a species-specific character in cephalopod taxonomy.

PMID- 15714943
TI  - The binding site for allosteric modulators of AMPA receptor.

PMID- 15714944
TI  - Weakly bound hydrogen and deuterium pairs in UV-photosensitized frozen aqueous
      solutions of KH2PO4 and KD2PO4.

PMID- 15714945
TI  - Differences in substrate specificity of the cholinesterase activity of nervous
      tissue of squids may be used in taxonomy.

PMID- 15714946
TI  - The role of solvent polarity in the mechanism of action of biologically active
      compounds at ultralow concentrations.

PMID- 15714947
TI  - Optimizing the model of population dynamics in the "predator-prey" system.

PMID- 15714948
TI  - Is the "chitin repair" mechanism universal in yeast?

PMID- 15714949
TI  - Determination of permeability of yeast plasma membrane for amphiphiles.

PMID- 15714950
TI  - The promoter region of the yellow gene of Drosophila melanogaster contains excess
      regulatory elements.

PMID- 15714951
TI  - Spectrophotometric study of specific features of the interaction between Ca2+ and
      anticoccidial benzylidenaminoguanidine derivatives containing an electron-donor
      or electron-acceptor substituent.

PMID- 15714952
TI  - Classification of interactions between populations: an optimization approach.

PMID- 15714953
TI  - Phloem unloading and activity of enzymes hydrolyzing sucrose in the apex of the
      growing root.

PMID- 15714955
TI  - Interaction between Su(Hw) insulators regulates cis- and trans-activity of the
      miniwhite gene enhancer.

PMID- 15714954
TI  - DNA-binding and antiviral activity of bis-netropsins containing clusters of
      lysine residues in the N-terminal region.

PMID- 15714956
TI  - [The principles and pitfalls on using Doppler ultrasonography during surgery].

PMID- 15714957
TI  - [Surgical anatomy and techniques in Dolenc approach].

PMID- 15714958
TI  - [Intra-arterial administration of fasudil hydrochloride: duration of action].
AB  - Intra-arterial infusion (IA) of fasudil hydrochloride for cerebral vasospasm is
      performed in many institutions and is associated with few side effects.
      Nonetheless, as optimum dose and duration of action remain unknown, the present
      study aimed to clarify these variables. We performed intra-arterial injection of
      fasudil hydrochloride for eight patients with cerebral vasospasm 7-13 days after
      subarachnoid hemorrhage. Fasudil hydrochloride was administered via the internal
      carotid artery without selective microcatheterization, at a concentration and
      speed of 30 mg/20 ml/10-15 min, using a total dose of 30-60 mg. Cerebral
      angiography was used to measure change in blood vessel diameter at 19 points, and
      perfusion CT was used to detect changes in cerebral blood perfusion (CBP),
      cerebral blood volume (CBV), and mean transit time (MTT) at 12 hemispheres.
      Investigations were performed before IA, immediately after IA (post IA), and 4.5
      to 6 hours later. For central vessels, (A1, M1) mean change in diameter (cm)
      measured pre IA, post IA, and 4.5-6 hours later was 1.2 +/- 0.68, 1.5 +/- 0.72,
      and 1.2 +/- 0.7, respectively. For peripheral vessels (peripheral to A1, M1, and
      the ophthalmic artery) change in diameter (cm) was 0.65 +/- 0.16, 0.97 +/- 0.24,
      and 0.71 +/- 0.24, respectively. Average CBP (m/100g/min) in the infused
      hemisphere at pre IA, post IA, and 4.5-6 hours later was 41.6 +/- 3.56, 46.4 +/-
      5.82, 41.6 +/- 7.42, respectively. Average CBV (ml/100g) was 2.72 +/- 0.21, 2.73
      +/- 0.21, 2.91 +/- 0.42, respectively and average MTT (sec) was 5.16 +/- 0.38,
      4.57 +/- 0.70, 5.55 +/- 1.0, respectively. Changes in peripheral vessel diameter
      and in MTT were statistically significant. Therefore, when performing intra
      arterial administration of fasudil hydrochloride, clinicians should be aware that
      vasodilator effect is less than 6 hours.

PMID- 15714959
TI  - [Dural arteriovenous fistula involving the cavernous sinus as the cause of
      intracerebral venous hemorrhage: a case report].
AB  - A case of cavernous sinus dural arteriovenous fistula (CS-DAVF) presenting
      intracerebral venous hemorrhage was reported. An 81-year-old woman was suffered
      from generalized convulsion accompanied by right conjunctival hyperemia and
      edema. Computed tomography scan revealed intracerebral hematoma involving right
      putamen and perifocal edema extraordinarily expanded to inferior part of the
      right frontal lobe and insular cortex. Cerebral angiography showed a CS-DAVF with
      retrograde leptomeningeal venous drainage (RLVD) not only to superficial middle
      cerebral vein but to basal vein of Rosenthal (BVR). Transvenous embolization was
      performed using mechanically detachable coils and free fibered platinum coils.
      After embolization, RLVD disappeared and conjunctival symptoms were improved.
      Hemorrhagic risk of this patient was discussed, based on her angiographical
      findings. We speculated that deep venous drainage to BVR through uncal vein, in
      case with poor venous collateral geometry, is one of the risk factor of cerebral
      hemorrhage.

PMID- 15714960
TI  - [Novel stent/CEA strategy for patients with bilateral carotid artery stenosis and
      coronary artery disease: report of 2 cases].
AB  - Recently, there are increasing numbers of patients with occlusive carotid artery
      disease and coronary artery disease. Simultaneous or two-staged surgery for both
      lesions has been recommended for these patients to reduce the incidence of
      perioperative complications. However, therapeutic options for the patients with
      bilateral carotid artery stenosis and coronary artery disease have not been
      established. In this report, we describe two patients who successfully underwent
      carotid endarterectomy (CEA) and carotid artery stenting (CAS) on each carotid
      artery in parallel with coronary artery bypass grafts (CABG). A 49-year-old male
      with severe stenosis of the bilateral internal carotid artery (ICA) and heart
      failure underwent CAS on the right side. Next day, he successfully underwent CABG
      and CEA on the left side at the same time. A 62-year-old male with severe
      stenosis of the bilateral ICA and coronary artery disease underwent CAS on the
      right side and CEA on the left side with an interval of 7 days. Subsequently,
      CABG was performed uneventfully. No perioperative complication occurred in either
      patient. The results suggest that combination therapy of CAS and CEA would be a
      valuable option for patients with complex carotid/coronary artery diseases.

PMID- 15714961
TI  - [Ruptured internal carotid -posterior communicating artery aneurysm associated
      with an anomalous hyperplastic anterior choroidal artery and aneurysm: case
      report].
AB  - We report a rare case of a ruptured internal carotid-posterior communicating
      artery (IC-PcomA) aneurysm associated with an anomalous hyperplastic anterior
      choroidal artery (AchoA) and aneuysm. A 64-year-old woman was admitted to our
      hospital because of a sudden onset of headache. CT scan showed subarachnoid
      hemorrhage. Left internal carotid angiograms showed a saccular aneurysm at the IC
      PcomA region. Left posterior cerebral artery filling from the fetal type PcomA
      and an anomalous hyperplastic AchoA originating from the internal carotid artery
      (ICA) were also revealed. Left vertebral angiograms (Allcock test) revealed the
      left ICA and an anomalous hyperplastic AchoA via the fetal type PcomA. The
      patient was surgically treated through the left pterional transsylvian approach.
      The ruptured aneurysm was observed at the IC-PcomA region. The unruptured small
      aneurysm was found on just distal to the ruptured aneurysm. The PcomA and an
      anomalous hyperplastic AchoA were not observed behind the ICA. To prevent
      bleeding, the ruptured aneurysm and unruptured small aneurysm were clipped.
      Postoperative left internal carotid angiograms demonstrated no aneurysm was
      observed at the IC-PcomA region. The patency of the fetal type PcomA and an
      anomalous hyperplastic AchoA were preserved. The 7 reported cases of a
      intracranial aneurysm associated with an anomalous hyperplastic AchoA with our
      case are reviewed and their neuroradiological and clinical features are
      discussed.

PMID- 15714962
TI  - [Four cases of spontaneous spinal epidural hematoma].
AB  - Spontaneous spinal epidural hematoma (SSEH) is a rare clinical entity. Although
      approximately 500 cases have been reported, controversy exists concerning timing
      of the treatment and the validity of decompression surgery. We recently
      encountered four cases of SSEH. Evacuation of the hematoma was carried out in two
      patients with severe or persistent neurological deficits. Other two patients were
      treated conservatively because of the rapid resolution of the symptoms. All four
      patients improved after the treatment; three patients fully recovered and one
      patient required rehabilitation for moderate quadriparesis. Many previous reports
      recommended decompression surgery within 48 hours after the onset, however, one
      patient in our series fully recovered after surgery 4 days after the onset. We
      reviewed 183 operative cases of SSEH with incomplete neurological deficits in the
      literature and found that 93% of the patients who underwent surgery more than 48
      hours after symptom onset showed good neurological recovery. Conservative
      treatment should be undertaken for rapidly improving patients, but surgical
      intervention should be considered in symptomatic patients regardless of the time
      from the onset.

PMID- 15714963
TI  - [Putaminal hemorrhage in a case of Turner's syndrome with hyperaldosteronemia].
AB  - A case of Turner's syndrome complicated with intracerebral hemorrhage in a 21
      year-old female is presented. The patient experienced acute onset of
      unconsciousness and the left-sided hemiparesis due to the right-sided putaminal
      hemorrhage. Severe hypertension was seen at the hospitalization. Cerebral
      angiography revealed no vascular lesion other than the displacement of
      lenticulostriate arteries. Emergent surgical evacuation of the hematoma was
      successfully performed with her favorable outcome. Postoperatively, several
      hormonal tests indicated hyperaldosteronemia secondary to the increased levels of
      ACTH and renin as a result of hyper-response to the environmental stress, leading
      to critical hypertension. Other examinations including CT scan, MRI, MRA, and
      laboratory data showed no abnormalities suggestive of renal lesions. It is
      supposed that hypertension, as a frequent presenting feature, should be strictly
      controlled in Turner's syndrome from the first time of diagnosis.

PMID- 15714964
TI  - [Mechanism of prostate cancer development].

PMID- 15714965
TI  - [Prostate cancer. Introduction].
AB  - Basic, epidemiological and clinical issues to be solved on prostate cancer were
      discussed as a preface. Sharp increase of prostate cancer incidence in Asian
      countries, almost constant level of latent cancer are intriguing epidemiological
      and pathological issues. Treatment of locally advanced prostate cancer, hormone
      refractory prostate cancer has been a long-standing clinical challenge. New
      radiotherapy is expected for further advancement. Heterogeneity, clonility,
      multiplicity of prostate cancer are interesting pathological challenges.

PMID- 15714966
TI  - [Summary of 'General Rule for Clinical and Pathological Studies on Prostate
      Cancer (the 3rd Edition)'].
AB  - 'General Rule for Clinical and Pathological Studies on Prostate Cancer(The 1st
      edition)' was published at 1985 by Japanese Urological Association and The
      Japanese Society of Pathology. It was revised in 1992 and the 2nd edition was
      published. Current diagnostic tests including prostate specific antigen (PSA) and
      biopsy technique have changed diagnosis and treatment of prostate cancer greatly.
      The 3rd edition was published in 2001 based on these changes. Here, the feature
      of the 3rd edition is outlined.

PMID- 15714967
TI  - [Descriptive epidemiology of prostate cancer in Japan and Western countries].
AB  - We summarized descriptive epidemiology of prostate cancer in Japan and compared
      it with that in Western countries. In Japan, the mortality and incidence rates
      have been increasing particularly in the elderly. The age-adjusted mortality rate
      (per 100,000 population) rose from 0.5 in 1950 to 8.6 in 2000 and so did the age
      adjusted incidence rate from 7.1 in 1975 to 19.9 in 1998 (rates were adjusted to
      the 1985 Japanese Model Population). In 1993 to 1997, the age-adjusted mortality
      rate in Japan was about one fifth to half of those in Western countries. Although
      PSA(prostate-specific antigen) screening may have apparently elevated the
      incidence rate in the US and some European countries, we did not find such a
      screening effect in Japan.

PMID- 15714968
TI  - [Molecular analysis for prostate cancer].
AB  - The molecular and biochemical mechanisms contributing to the development and
      progression of prostate carcinogenesis are still unknown. Recent technologies
      such as, real-time PCR, microarray, and laser capture microdissection, have
      accelerated the study of the molecular events involved in prostate cancer. The
      expression and function of numerous genes have been shown to be altered in
      prostate cancer. Such gene regulations are involved in cell cycle, signal
      transduction pathways, or gene expression. Analysis of the genes during prostate
      cancer progression has provided a better understanding of the basis of the
      disease. This review summarises current knowledge of the molecular analysis for
      prostate cancer.

PMID- 15714969
TI  - [Polymorphisms of hormone-related genes and prostate cancer risk in Japan].
AB  - Accumulation of information about genetics and epigenetics has accelerated
      research investigating the inherent individual variation in cancer
      susceptibility. Gene polymorphisms, in particular single nucleotide
      polymorphisms, are being evaluated for their role in various cancers including
      prostate cancer. Especially, polymorphisms of hormone-related genes such as
      steroid-hormone receptors in prostate cancer have been recently focused and used
      in molecular epidemiology. In this article, we present data from the molecular
      epidemiology about Japanese prostate cancer using polymorphisms of hormone
      related genes and offer suggestions for further research.

PMID- 15714970
TI  - [Clinical and pathological staging of prostate cancer].
AB  - In Japan, UICC TNM staging system is widely accepted and used for clinical and
      pathological classification of prostate cancer. "General rule for clinical and
      pathological studies on prostate cancer" was also edited by Japanese urological
      association and the Japanese society of pathology. In this book, clinical staging
      system modified from Jewett staging system is demonstrated. Though both staging
      systems are widely used in clinical practice to select treatment and speculate
      prognosis after treatment, there still exists many limitations and unreasonable
      problems that must be solved in the future. In this paper, these staging systems
      with their specific problems and new grouping trials will be introduced.

PMID- 15714971
TI  - [Histopathological features of prostate cancer].
AB  - The diagnosis of prostatic cancer present in a limited amount within needle
      biopsy tissue, is often challenging. The most common mimickers giving rise to
      false-positive cancer diagnosis are atypical adenomatous hyperplasia, prostatic
      intraepithelial neoplasia, atrophy and post-atrophic hyperplasia. Various
      diagnostic criteria including assessment of basal cells should be used for
      diagnosis of limited carcinoma. Immunohistochemical staining for both basal
      cells, such as 34betaE12 and p63, and AMACR, which label the cytoplasm of
      approximately 80% of prostatic adenocarcinoma, may be a useful adjunct in the
      diagnosis of limited prostatic cancer. However there are problems with both
      sensitivity and specificity. When the glands lacking sufficient criteria to
      establish a definitive carcinoma is present, we use the term 'atypical small
      acinar proliferation'.

PMID- 15714972
TI  - [Recent advancement in diagnosis and treatment of prostate cancer--general
      concepts].
AB  - Prostate cancers which are diagnosed during PSA screening include a significant
      number of clinically insignificant cancers. Useful strategy for needle biopsy is
      warranted. In addition, useful strategy for the timing of radical therapy for
      localized prostate cancer is warranted to be established. These strategies are
      essential to avoid over-diagnosis and over-treatment.

PMID- 15714973
TI  - [PSA-based parameters].
AB  - Serum prostate-specific antigen (PSA) is used for the screening and early
      detection of prostate cancer. We are, however, confronted with the dilemma that a
      significant number of unnecessary biopsies are unavoidable especially in the
      serum PSA range of 4 to 10ng/ ml. It has been reported that age-specific PSA
      reference ranges, PSA velocity, PSA molecular forms and volume-adjusted PSA are
      valuable tools to improve specificity for early diagnosis of prostate cancer. In
      recent years, free PSA has been demonstrated to be composed of several isoforms
      including pPSA, BPSA and so on. Clinical values of these new PSA isoforms as well
      as human glandular kallikrein 2 are anticipated to be fully investigated to
      reduce unnecessary biopsies without missing a significant number of prostate
      cancer in the near future.

PMID- 15714974
TI  - [MR imaging and MR spectroscopy in prostate cancer].
AB  - Prostate cancer is the most common cancer in western men. The morbidity in
      Japanese men is also increasing. This article reviews MR imaging and MR
      spectroscopy used for the diagnosis and management of prostatic cancer.
      Discussion emphasizes techniques for routine MR imaging, imaging findings, and
      the value of MR imaging in patients with prostatic cancer. The new and promising
      technique of MR spectroscopy and 3T MR imaging also will be introduce.

PMID- 15714975
TI  - [Prostate biopsy].
AB  - Multiple core prostate biopsy was introduced by Eskew et al in 1995, and many
      procedures of multiple core biopsy were proposed. These methods showed importance
      of taking samples from lateral part of peripheral zone, transition zone or apex.
      Cancer detection rates were dramatically increased in comparison with those
      detected by traditional systematic sextant biopsy (SSB). Utilization of the
      template, age-volume adjusted parameter or apical horn biopsy facilitated the
      efficacy of multiple core biopsy. Furthermore, these techniques could contribute
      to accurate estimation of pathological findings. Multiple core prostate biopsy
      would get to be more important in modern prostate specific antigen era when more
      T1c or more early stage prostate cancer would be detected.

PMID- 15714976
TI  - [Radical prostatectomy for localized prostate cancer].
AB  - With widespread use of PSA screening, radical prostatectomy has gained popularity
      among Japanese urologists over the last decade. Recent understanding of pelvic
      anatomy and improvement in surgical technique have substantially reduced its
      morbidity. Early recovery of urinary continence is possible and improvement of
      sexual function after surgery may be enhanced by use of sildenafil and nerve
      reconstructive surgery. As prostate cancer is increasingly diagnosed at early
      stages and therefore with more favorable survival outcomes, the basis on which
      patients select primary therapy has shifted toward considerations of health
      related quality of life. Accordingly, QOL assessment has become an important form
      of outcomes based research that may weigh heavily on the treatment selection by
      patients.

PMID- 15714977
TI  - [Clinical outcomes and problems in laparoscopic radical prostatectomy].
AB  - We evaluated the clinical outcome and problem of laparoscopic radical
      prostatectomy (LRP) for 115 prostate cancer patients. Mean (+/- SD) operative
      time was 294 +/- 57.5 min. and mean blood loss was 409.5 +/- 336.4 g. Mean
      duration of urethral catheter indwelling was 4 +/- 4.9 days and mean
      postoperative hospital stay was 8 +/- 4.6 days. Fifty one and 83% of the patients
      recovered urinary continence one month and 3 months after surgery in the latest
      procedure, respectively. Positive surgical margin was seen in 18 patients (15.7%)
      in total, but in 6 patients (6.6%) with pT2 > or = disease. Chemical relapse was
      seen in 14 patients (14.4%). Although oncological results of LRP are compatible
      to those of RRP, delay of early recovery of urinary continence is still the
      problem.

PMID- 15714978
TI  - [Radical prostatectomy with neoadjuvant hormone therapy for cT3 prostate cancer].
AB  - The efficacy of neoadjuvant hormone therapy and radical prostatectomy for cT1-2
      prostate cancer have been reported to be negative from some randomized
      prospective studies. On the other hand, radical prostatectomy alone for cT3
      prostate cancer is understood as out of indication because of high rate of
      positive surgical margin and PSA failure. Several investigators have examined the
      role of neoadjuvant hormone therapy before radical prostatectomy for cT3 prostate
      cancer to improve outcome. This document was reviewed the literature whether
      neoadjuvant hormone therapy is beneficial or not, for organ confined prostate
      cancer and for locally advanced prostate cancer, and presented our extended
      resection of prostate with neoadjuvant hormone therapy is improved the results in
      cT3 prostate cancer.

PMID- 15714979
TI  - [Radiation therapy for prostate cancer].
AB  - The advent of image-guided or CT-based treatment planning, such as 3D-conformal
      or intensity modulated radiation therapy has allowed safe delivery of high- dose
      radiation therapy in men with prostate cancer with an acceptable rate of side
      effects and complications. External-beam radiation therapy designed to decrease
      exposure of normal tissues using methods such as 3D-conformal treatment planning
      is under clinical evaluation. Randomized trial shows escalation of radiation dose
      leads to improved biochemical disease-free survival for a select group of
      patients. Interstitial brachytherapy has been also employed for patients with
      selected for favorable characteristics, including low Gleason score, low PSA
      level, and stage T1 to T2 tumors. Long-term follow-up of patients is necessary to
      assess treatment efficacy and side effects.

PMID- 15714980
TI  - [Heavy particle therapy for prostate cancer].
AB  - Heavy particle (ion) beams are characterized by high relative biological
      effectiveness and improved dose distribution. To establish heavy ion therapy for
      prostate cancer, three trials have been conducted. For 247 patients with T1b-T3
      cancer, carbon ion beam was irradiated 20 times/5 weeks with or without endocrine
      therapy. Overall and cause-specific survivals were excellent and local control
      was achieved in all patients except one. Grade 3 late morbidity of rectum and/or
      bladder/urethra was developed in 7 cases who received higher dose. Thus, total
      dose was decreased to 66 GyE and the radiation field was coned down during the
      treatment. In conclusion, carbon ion therapy is expected to exert excellent
      effect in the treatment of localized and locally advanced prostate cancer.

PMID- 15714981
TI  - [Chemotherapy for prostate cancer].
AB  - The clinical significance of chemotherapy for patients with hormone refractory
      prostate cancer(HRPC) is still controversial. Some randomized-controlled trials
      represented that mitoxantrone combined with prednisone (or hydrocortisone)
      provided palliative benefit to patients with HRPC. These treatments are well
      tolerated by elderly patients. On the other hand, the high PSA response rates
      have been observed in trials with both estramustine and taxane, however, higher
      toxicity was also recognized. The most relevant endpoint is not only palliative
      efficacy but also survival in these trials. Recently, the improvement of survival
      with docetaxel-based chemotherapy was reported. Further studies with
      chemotherapeutic agents will be needed to provide patients of HRPC good quality
      of life and longer survival.

PMID- 15714982
TI  - [Treatment of androgen-independent hormone refractory prostate cancer using
      docetaxel].
AB  - Although prostate cancer patients with metastatic lesion initially respond to
      androgen ablation therapy, almost patients develop to hormone-refractory states.
      The optimal treatment for men with hormone refractory prostate cancer (HRPC) has
      not been established. Docetaxel is a semisynthetic taxane that inhibit tumor
      growth by induction of microtubule stabilization and promotion of bcl-2
      inactivation, which induce apoptosis. Docetaxel as single agent has significant
      anti-tumor effect in HRPC patients. Docetaxel combined with estramustine or other
      antimicrotubular agents have shown further significant cytotoxicity in HRPC
      patients. In the United States, Food and Drug Administration (FDA) approved
      docetaxel, injection in combination with prednisone for the treatment of patients
      with advanced metastatic prostate cancer in 2004.

PMID- 15714983
TI  - [Hormonal therapy for prostatic cancer--state of the art].
AB  - Following the studies of Huggins and colleagues in 1941, the hormonal treatment
      of prostatic cancer has been aimed at neutralizing the influence of testicular
      androgens through surgical castration or the administration of high dose
      estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen
      antagonist for prostatic cancer. Various reports demonstrated a beneficial effect
      for combined androgen blockade using nonsteroidal antiandrogens for advanced
      prostatic cancer through meta-analysis of published randomized control trials. In
      Japanese status, a combined androgen blockade is popular for advanced prostatic
      cancer as well as local cancer by J-Cap survey. There is a lot of controversy
      about adjuvant hormonal therapy for prostatic cancer including intermittent
      hormonal therapy, but the results are not gotten yet.

PMID- 15714985
TI  - [Quality of life after radical prostatectomy].
AB  - Prostate cancer is increasingly detected at early stages and patients can choose
      various forms of treatment which have favorable survival outcomes. Radical
      prostatectomy is a major procedure for treating early stage prostate cancer
      curatively. The instruments of measuring health related QOL (HRQOL) accurately
      for early prostate cancer treatment were developed. Some of the instruments were
      useful in Japan after translating into Japanese and pilot testing. Many authors
      have reported QOL data after radical prostatectomy. These data suggested that
      general and urinary domains of HRQOL recovered rapidly after radical
      prostatectomy, but recovery of sexual domains of HRQOL took longer. Recently
      several authors have reported that HRQOL were affected with ethnic and cultural
      differences. These results strongly suggested a need for longitudinal surveys in
      Japanese patients.

PMID- 15714984
TI  - [Neoadjuvant hormonal therapy for prostate cancer].
AB  - Preoperative neoadjuvant hormonal therapy is still controversial. This therapy's
      purpose is downstaging prostate cancer at radical prostatectomy and thereby
      improving the prognosis of prostate cancer. It has been repeatedly demonstrated
      that hormonal therapy causes significant alterations in the gross and microscopic
      appearance of the prostate. Most studies report a significant improvement in
      surgical margins and downstaging. However, it remains to be seen if the favorable
      findings lead to an improved outcome after radical prostatectomy. Our study
      showed 6-12 months neoadjuvant hormonal therapy with maximal androgen blockade
      did not lead to the improved result in long term follow-up. Because, PSA failure
      was observed 25% of the cases which received neoadjuvant hormonal therapy prior
      to radical prostatectomy.

PMID- 15714986
TI  - [Risk factors and current chemoprevention studies in prostate cancer].
AB  - There are no established risk factors for prostate cancer other than age, ethnic
      group, and family history. For dietary factors, the WCRF/AICR reported that diets
      high in vegetables were possibly protective, and that regular consumption of red
      meat, fat, saturated/animal fat, and milk and any products possibly increased
      risk. Among nutritional factors, a protective effect of lycopene, vitamin E,
      selenium, and perhaps fish oil and phytoestrogens appear particularly promising,
      although no definite answers have yet emerged. Although hormonal influences are
      biologically plausible, observational studies of androgen have not produced
      consistent results. While, insulin-like growth factor 1 could be a risk factor.
      Based on these evidences, several chemoprevention trials were launched using 5
      alpha reductase inhibitor, selenium, vitamin E and so on.

PMID- 15714987
TI  - [Sentinel lymph node concept in prostate cancer].
AB  - A sentinel node (SN) validation study using a radioactive tracer and back-up
      extended pelvic lymph node (LN) dissection was performed in 40 patients with non
      metastatic prostate cancer (PCa). The results of the study were favorable with
      sensitivity, specificity, and accuracy of SN biopsies revealed 90%, 100% and
      97.5%, respectively. Based on our promising results to date, we examined the
      utility of SN navigation surgery (SNNS) in patients with LN metastasis
      probability of 10% or less on Partin tables. Endoscopic mini-laparotomy surgery
      was applied to our SN biopsies in 9 patients with clinically localized PCa. SNs
      were successfully resected in 7 of these patients. Endoscopic minilaparotomy SNNS
      is a less invasive form of radical surgery for prostate cancer with accurate
      diagnosis of LN status.

PMID- 15714988
TI  - [Prostate cancer gene therapy].
AB  - With the advance in genetic engineering, tumor biology and immunology, gene
      therapy has been recognized as a promising new treatment option for cancer
      including prostate cancer. Several clinical trials of prostate cancer gene
      therapy are currently underway, using therapeutic genes which include suicide
      genes, immunomodulatory genes, tumor suppressor genes and anti-oncogenes.
      Although the gene therapy for prostate cancer as a clinical alternative is still
      early stage which requires several technological breakthrough, some information
      obtained from clinical trial indicates full potential of prostate cancer gene
      therapy. Concordant progress both in the basic research and gene therapy
      technology will make prostate cancer gene therapy ready for wide-scale of
      practice in the future. In this report, general concept and current progress in
      prostate cancer gene therapy are summarized.

PMID- 15714989
TI  - [Novel molecular targeting therapeutics for prostate cancer].
AB  - Our previous study demonstrated that Angiotensin II (Ang-II) which is well known
      to be a main peptide of the renin-angiotensin system could activate the cell
      proliferation of prostate cancer as well as EGF, and an Ang-II receptor
      blocker(ARB) could inhibit it through the suppression of phosphorylation of MAPK
      and STAT3. Also, ARB exerted an antiproliferative effect on prostate cancer
      through paracrine factors from stromal cells. We believe that ARBs have the novel
      ability to suppress the development or progression of prostate cancer.
      Furthermore, based on the idea that inhibition of G protein-coupled receptor
      signaling in cancer and stromal cells could suppress prostate cancer growth, a
      novel treatment such as molecular targeting therapy to overcome this devastating
      disease could be possible in the future.

PMID- 15714990
TI  - [High-intensity focused ultrasound for localized prostate cancer].
AB  - High-intensity focused ultrasound (HIFU) is a noninvasive treatment that induces
      complete coagulative necrosis of a tumor at depth through the intact skin. We
      evaluated a biochemical disease-free rate, safety and morbidity for localized
      prostate cancer treated with HIFU. A total of 132 consecutive patients with stage
      T1c-2N0M0 localized prostate cancer underwent HIFU using Sonablate-500 (Focus
      Surgery, Indianapolis, USA). The 5-year biochemical disease-free rate in all
      patients was 67%. The 5-year biochemical disease-free rates for patients with a
      pretreatment PSA less than 10 ng/ml, 10.01 to 20.0 ng/ml, 20.01-30.0 ng/ml and
      more than 30.01 ng/ml were 88%, 67%, 34% and 13% (log rank test, p < 0.0001),
      respectively. HIFU therapy appears to be a safe, efficacious and minimally
      invasive therapy for patients with localized prostate cancer.

PMID- 15714991
TI  - [New biomarkers for prostate cancer].
AB  - Prostate cancer is one of the most common cancers in Western men. In Japan, the
      incidence of this malignancy is increasing. Recent advances in molecular biology
      brought new biomarkers to prostate cancer diagnosis. In this article, we describe
      new biomarkers including serum and genetic and histochemical markers for
      screening, staging and drug selection for the management of prostate cancer
      patients.

PMID- 15714992
TI  - [Psychoses in patients with Parkinson's disease; their frequency, phenomenology,
      and clinical correlates].
AB  - The frequency, phenomenology, and risk factors of hallucinations and delusions
      were investigated in 64 consecutive inpatients with Parkinson's disease. Fifty
      patients were admitted to our hospital with symptoms related to Parkinson's
      disease: psychiatric problems 27 (psychosis 22; anxiety 2; depression 2; mania
      1): motor symptoms, 20 (wearing-off 5; akinesia 4; freezing 4; postural
      instability 4; dyskinesia 2; tremor 2; dystonia 1), and sensory symptoms, 3.
      Fourteen patients were admitted with other medical problems (pneumonia 4;
      cerebral infarction 3; bone fracture 3; lumbago 2; seizure 1; cat bite 1).
      Totally 49 patients had psychiatric problems. Psychosis was present in 43
      patients, dementia in 10, depression in 8, mania in 1, anxiety in 10, agitation
      in 6, stereotypy in 2, and hypersexuality in 2. Of the 43 patients with
      psychoses, 40 presented with visual hallucinations, 18 with auditory
      hallucinations, and 23 with delusions. To determine what the clinical correlates
      with the severity of psychosis were, we divided the patients into 3 groups: the
      severe group, 22 patients admitted because of psychotic symptoms; the mild group,
      21 patients admitted because of problems other than psychosis but presenting
      psychotic symptoms; and the control group, 21 patients who had no psychotic
      symptoms. Incidences of auditory hallucinations and delusions were higher in the
      severe group as compared to the mild group. Patients in the severe group had
      higher Hoehn-Yahr stages, lower Mini-Mental State Examination scores, decreased
      H/M ratios of cardiac 123I-MIBG uptake, and lower frequencies of background
      activity on electroencephalograms. There were no differences in age at admission,
      age at onset of Parkinson's disease, duration of illness, amounts of levodopa and
      dopamine agonists received, Hamilton's depression rating scores, and brain MR
      findings, including atrophy and ischemic changes. Emergence of psychotic symptoms
      in parkinsonian patients appears to be clearly associated with impaired cognitive
      function. Therefore, it may be associated with the disease process itself. Terms
      such as dopaminomimetic or levodopa-induced psychosis may not be appropriate when
      describing psychosis in Parkinson's disease.

PMID- 15714993
TI  - [Clinical classification for lacunar infarct. An investigation of 130 consecutive
      cases of lacunar infarctions].
AB  - A lacunar infarct is defined as the occlusion of a single perforating artery.
      Certain researchers have proposed that patients with lacunar infarcts can be
      classified into two clinically distinct entities: patients with a single,
      symptomatic lacunar infarct, and patients with multiple lacunar infarcts together
      with hypertension and leukoaraiosis. The present study attempted to delineate the
      characteristics of lacunar infarcts and evaluate the validity of the
      aforementioned hypothesis. A total of 130 consecutive patients with first-time
      symptomatic lacunar infarct were studied. All patients were dichotomized into two
      groups according to two different kinds of models as follows. Model-1: patients
      with a single lacune and patients with multiple lacunes; and Model-2: patients
      with large lacune and patients with small lacune. Associated factors for the
      multiple lacune group compared with the single lacune group as well as the large
      lacune group compared with the small lacune group, were analyzed by multivariate
      logistic regression analysis. Associated factors included age, sex, hypertension,
      diabetes mellitus, dyslipidemia, smoking, extracranial and intra-cranial vascular
      lesions, extent of lacunes and white matter lesions, progression status and blood
      pressure in the acute stage, and coagulation markers such as fibrinogen, thrombin
      antithrombin complex, D-dimer, beta-thromboglobulin, platelet factor 4. Results
      for Model-1: hypertension (age-and sex-adjusted OR: 2.58, p = 0.017) and elevated
      systolic blood pressure (>160mmHg for the mean value during the first post-ictal
      week; OR: 2.55, p = 0.016) were significantly associated with the multiple lacune
      group. Large lacunes (>10mm in diameter) were negatively associated with the
      multiple lacune group (OR: 0.38, p = 0.017). Association between confluent white
      matter lesions and the multiple lacune group approached significance (OR: 2.16, p
      = 0.056). Results for Model-2: female sex (OR: 0.39, p = 0.021), mild stenosis of
      intracranial and extracranial arteries (<25%) (intracranial; OR: 5.42, p =
      0.0042, extracranial; OR: 3.30, p = 0.016), progressing stroke (OR: 6.77,
      p<0.0001), and high levels of TAT (>3ng/ml) (OR: 2.80, p = 0.039) were
      significantly associated with the large lacune group. Multiple lacunes (OR: 0.38,
      p = 0.016) and confluent white matter lesions (OR: 0.28, p = 0.007) exhibited a
      significant negative association with the large lacune group. In conclusion,
      underlying vasculopathy in the presence of multiple lacunes may correspond to
      lipohyalinosis resulting from hypertension. Moreover, large lacune may correspond
      to microatheroma at the orifice of penetrating arteries.

PMID- 15714994
TI  - [Posterior leukoencephalopathy syndrome presenting with bilateral ataxie optique:
      a case report].
AB  - We report a 45 years old right-handed woman who developed acute respiratory
      distress syndrome (ARDS) after the operation for rupture of an ovarian cyst. One
      week after the onset of ARDS, she presented visual disturbance and Gerstmann
      syndrome. MRI T2-weighted images demonstrated abnormal high intensity lesions
      involving the gray and white matter of the occipital lobes bilaterally extending
      to the parietal lobes. Based on these findings, she was diagnosed as having
      posterior leukoencephalopathy syndrome (PLES). Her neurologic symptoms gradually
      improved, however, she started to complain of difficulty in grasping a cup placed
      on her peripheral visual fields. Neurological examination revealed no visual
      disturbance, weakness or cerebellar ataxia. She could easily reach objects
      presented in the central visual field, however, she could not grasp objects
      presented peripheral visual fields, while she was looking straight ahead. This
      disorder was observed both in the right and left visual field, whether she used
      the right hand or the left hand. We thought she had ataxie optique of Garcin. She
      was noted to have bilateral both direct and crossed ataxie optique. Ataxie
      optique is characterized by disturbance in reaching objects presented in the
      peripheral visual field. The underlying pathophysiologic mechanism is believed to
      be disconnection of the fibers between the primary visual area and the angular
      gyrus at the parietooccipital junction. Crossed ataxie optique consisting of
      difficulty in reaching objects presented in the contralateral visual field
      believed to be caused by disconnection of crossed pathways of the corpus
      callosum. Ataxie optique in our patient can be explained by disconnection of both
      direct and crossed fibers. Ataxie optique is sometimes unrecognized by the
      patient. Our patient suggests that ataxie optique may well be a symptom of PLES.

PMID- 15714996
TI  - [Evaluation of two patients with SCA2 with frontal lobe dysfunction using brain
      SPECT with three-dimensional stereotactic surface projections (3D-SSP)].
AB  - We evaluated the cognitive impairment of two patients with genetically confirmed
      spinocerebellar ataxia type 2 (SCA2). Neurological examination revealed ignorance
      of his illness and Gegenhalten phenomenon in patient 1, and emotional
      incontinence in patient 2. Although their mental status evaluated by HDS-R or
      Mini-Mental State Examination (MMSE) was almost normal, the results of WAIS-R and
      Wisconsin Card Sorting Test (WCST) revealed the existence of intellectual decline
      and executive dysfunction. 3D-SSP SPECT demonstrated distinct hypoperfusion in
      bilateral frontal lobes, whereas brain MRI revealed no apparent cerebral atrophy
      in both patients. These results raise the possibility that frontal lobe
      dysfunction was observed in the early stages of SCA2, and that 3D-SSP SPECT is
      useful for evaluating the involvement of frontal lobe dysfunction in SCA2.

PMID- 15714995
TI  - [A patient with Vibrio vulnificus meningoencephalitis].
AB  - A 76-year-old man with liver cirrhosis and diabetes mellitus was admitted to our
      hospital because of bacterial meningoencephalitis. He had eaten raw fish 2 days
      before onset. He also developed septic shock, disseminated intravascular
      coagulation, adult respiratory distress syndrome and panophthalmitis of the right
      eye. Vibrio vulnificus was isolated from the blood culture. Extensive therapy
      including antibiotics and nafamostat methylate, resulted in full recovery except
      for right blindness. The necrotizing fasciitis, which is common with Vibrio
      vulnificus infection, had not been complicated in this patient.

PMID- 15714997
TI  - [A case of early stage CADASIL showing only dizziness and vertigo with a novel
      mutation of Notch 3 gene].
AB  - We report a 39-year-old woman who presented with only dizziness and vertigo for 2
      months. Neurological examination revealed no abnormalities except for
      hypereflexia on the left side extremities. Neurootological examination revealed
      no abnormalities. MRI of the brain demonstrated patchy hyperintensity areas on
      FLAIR images in the periventricular white matter and external capsule. Her
      grandmother had cerebral infarction and her father is suffering from multi
      infarct dementia. Her second older sister who similarly had dizziness and vertigo
      demonstrated similar MRI findings characterized by patchy hyperintensity areas in
      the white matter and external capsule even though she had no risk factors for
      atherosclerosis. Her third older sister also had dizziness and vertigo and had
      patchy hyperintensity areas in the white matter in her brain MRI even though she
      had no risk factors for atherosclerosis. Based on this family history, we
      suspected that she had cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL). Mutational analysis of Notch3 gene
      disclosed a novel missense mutation substituting arginine for cysteine at codon
      206 (C206R) in exon 4 of the Notch3 gene, confirming the diagnosis of CADASIL.
      Interestingly, similar dizziness and vertigo were present not only in the
      patient, but also in the other two sisters who had the same gene mutation as the
      patient. This report supports the idea that the external capsule lesion is one of
      the signs suggestive of CADASIL as a diagnosis.

PMID- 15714998
TI  - [An autopsy case of origin-unidentified meningeal carcinomatosis presenting with
      monoradiculopathy multiplex in the lower extremities].
AB  - A 54-year-old man with a history of partially dissected epidermoid cyst in the
      left cerebellopontine angle suffered from a slowly progressive dysesthesia and
      weakness in the lower extremities and trunk. Neurological examination revealed
      segmental muscular weakness and sensory disturbance in those regions, giving rise
      to the possibility of monoradiculopathy multiplex, as well as loss of tendon
      reflexes, dysuria and right facial nerve palsy. Electrophysiological studies
      indicated irregular motor axonopathy or neuronopathy and interruption of more
      central sensory pathways than the lumbosacral spinal nerve roots with spared
      peripheral sensory nerves. Although MRI demonstrated enhanced lesions in the
      cauda equina and lumbosacral leptomeninges, CSF cytology or a cauda equina biopsy
      showed no malignancy. His symptoms gradually progressed and he died 15 months
      after the onset. The autopsy failed to reveal any tumors in the general systemic
      internal organs. Histopathology demonstrated meningeal carcinomatosis with
      squamous-type carcinoma cells scattered in the cerebrospinal leptomeninges, and
      perineurium in almost all the spinal and cranial nerve roots, causing severe
      axonal degeneration. The dorsal root ganglions escaped tumor cell invasion.
      Absence of the malignant tumors in the systemic organs and the history of the
      operated epidermoid cyst indicate that the tumor may be the cause of the
      meningeal carcinomatosis in this case. Meningeal carcinomatosis almost always
      shows rapid progression and extremely poor prognosis with several month survival
      in general, and little attention has been paid that it can exhibit symptoms and
      signs of segmental involvement in the lumbosacral regions. Our present case
      prompts us to bear in mind that patients with this condition can survive fairly
      long, and raises the possibility that a careful neurological examination with
      segmental involvement will reveal such a feature more frequently than considered
      so far in this condition.

PMID- 15714999
TI  - [Abducens nerve palsy as the first manifestation of cavernous sinus sarcoidosis].
AB  - We report a 33-year-old man who presented with an acute onset of diplopia and
      orbitalgia. Neurological examination revealed right abducent nerve palsy. Brain
      MRI showed a gadolinium-enhancing mass lesion in the right cavernous sinus. Chest
      CT showed a small lymph node swelling in the subcarinal compartment. Serum
      angiotensin converting enzyme and lysozyme levels were within normal range.
      Biopsied lymph node in the left supraclavicular fossa showed non-caseating
      epitheloid granulomas, consistent with sarcoidosis. After oral administration of
      predonisolone, his right abducent nerve palsy ameliorated in a few days and
      completely disappeared by 6 weeks after treatment. Abducent nerve palsy can be
      the first clinical manifestation of cavernous sinus sarcoidosis.

PMID- 15715000
TI  - [A case of anterior cerebral artery dissection causing hemorrhagic infarction].
AB  - A 56-year-old man presented with weakness in his right arm and leg. Throbbing
      headache occurred several hours prior to his weakness. Brain CT obtained on day 3
      demonstrated low density areas in the medial part of the left frontal lobe.
      Cerebral angiography on day 14 demonstrated dilatation and narrowing of the left
      anterior cerebral artery (ACA) corresponding to "pearl and string sign". The
      diagnosis of spontaneous ACA dissection was established with clinical features,
      laboratory findings, and angiographic findings. Antiplatelet therapy was
      undertaken for the prevention of ischemic events. Serial Brain CT demonstrated
      hemorrhagic change in the area of infarction. However, there was no definite
      clinical deterioration. Antiplatelet therapy was withdrawn after hemorrhagic
      change was noted. Cerebral angiography on day 35 showed improvement of both
      dilatation and narrowing. Possible reperfusion injury caused by absorption of
      intramural hematoma seems to be responsible for hemorrhagic change. In patients
      with cerebral infarction due to dissection of intracranial arteries,
      antithrombotic therapy is controversial as hemorrhagic complications including
      hemorrhagic infarction as well as subarachnoidal hemorrhage can occur. Further
      accumulation of cases is required.

PMID- 15715001
TI  - [Bucillamine-induced dermatomyositis-like clinical features in a patient with
      rheumatoid arthritis].
AB  - A 78 year-old woman was admitted to our hospital because of subacutely
      progressive dysarthria, dysphagia, proximally dominant muscle weakness and
      erythema in the neck and back. She was diagnosed as having rheumatoid arthritis
      (RA) at the age of 60 and treated with bucillamine (BUC) for 8 years. Laboratory
      tests included a rheumatoid factor of 1,472U/ml. Serum creatine kinase level was
      slightly elevated. The activated T cells in the peripheral blood were markedly
      increased. Needle EMG demonstrated myogenic changes. The magnetic resonance image
      of the left upper arm showed diffuse muscle atrophy and inflammatory changes in
      the triceps muscle. The muscle biopsy revealed perivascular inflammatory cell
      infiltraton and type II fiber atrophy. A biopsy from the skin showed mild
      perivascular inflammatory cell infiltraton. According to the results of these
      findings, she was thought to have dermatomyositis due to BUC. After withdrawal of
      BUC followed by the administration of prednisolone 1mg/kg, her symptoms improved
      and activated T cells in the peripheral blood were decreased. In Japan, BUC is
      widely accepted as an effective drug in the treatment of RA, even though it is
      known to induce some autoimmune diseases. However, the mechanism of the
      development of autoimmune disease is unclear. We considered that the long-term
      use of bucillamine could trigger an autoimmune response such as an increase in
      activated T cells and the development of dermatomyositis-like clinical features
      in our patient. In conclusion, when RA patients treated with BUC show a clinical
      picture compatible with dermatomyositis, its causative relationship has to be
      considered.

PMID- 15715002
TI  - Assessing animal welfare needs in Banda Aceh, Indonesia.

PMID- 15715003
TI  - PrP genotypes of rare breeds of sheep in Great Britain.
AB  - In total 31,669 blood samples were collected from 1187 flocks of 27 rare breeds
      of sheep in the UK, and their genotype profiles at the prion protein locus were
      determined. The frequencies of the five alleles varied widely among the breeds
      and some had only two of the alleles and others had all five; the average was
      three. The average allele frequencies across all 27 breeds were 49.7 per cent for
      ARR, 4.4 per cent for AHQ, 2.7 per cent for ARH, 37.4 per cent for ARQ and 5.8
      per cent for VRQ. The highest frequencies for each allele were 90.7 per cent for
      ARR in the Leicester Longwool, 24.7 per cent for AHQ in the Hebridean, 68.7 per
      cent for ARH in the Manx Loghtan, 98.7 per cent for ARQ in the North Ronaldsay
      and 28.4 per cent for VRQ in the Boreray. All 27 breeds had the ARR allele, 21
      had AHQ, 11 had ARH, 26 had ARQ and 20 had VRQ.

PMID- 15715004
TI  - Field trial of a Caryospora species vaccine for controlling clinical coccidiosis
      in falcons.
AB  - A Caryospora species vaccine was prepared and used in an attempt to prevent
      infection and associated morbidity in falcons. A blind field trial was conducted,
      involving a vaccinated group of 20 birds and two control groups of seven and four
      birds, which were subsequently challenged with a live mixed-species vaccine.
      There was a statistically significant reduction in morbidity and shedding of
      oocysts in the vaccinated group compared with the control groups.

PMID- 15715005
TI  - Protection against bovine respiratory syncytial virus challenge following a
      single dose of vaccine in young calves with maternal antibody.
AB  - Twenty-one young calves with maternally derived antibody to bovine respiratory
      syncytial virus (BRSV) were divided into three groups of seven, each group
      balanced for BRSV antibody titre. The calves had no evidence of previous exposure
      to BRSV. The calves in one group were given a single dose of a monovalent
      modified live BRSV vaccine; the calves in the second group were given a single
      dose of an inactivated combined BRSV, parainfluenza virus type 3, Mannheimia
      haemolytica vaccine and the calves in the third group were left as unvaccinated
      controls. Three weeks after the single doses of vaccine, all the calves were
      challenged with BRSV. The clinical signs of disease were mild, and virus
      excretion was limited to two calves in the group given the inactivated vaccine,
      compared with six in the negative controls (P = 0.05) and five in the group given
      the live vaccine. The mean virus excretion titres after the challenge were not
      significantly different between the groups. There was little seroconversion
      before the challenge, but six of the seven calves in the group given the
      inactivated vaccine showed significant seroconversion within two weeks after the
      challenge, compared with only one calf in each of the other two groups (P =
      0.015).

PMID- 15715006
TI  - Control of bovine TB: preferences of farmers who have suffered a TB breakdown.

PMID- 15715007
TI  - L-2-hydroxyglutaric aciduria in a West Highland white terrier.

PMID- 15715008
TI  - Isolation of Brucella abortus from cattle and water buffalo in Brazil.

PMID- 15715009
TI  - Lack of specificity of a combination of Rappaport-Vassiliadis broth and XLT4 agar
      for the isolation of salmonellae from pig faeces.

PMID- 15715010
TI  - Detection of Leishmania infantum in canine peripheral blood.

PMID- 15715011
TI  - The Shipman reports: lessons and warnings.
AB  - The reports from the Shipman inquiry will lead to changes in the way the medical
      profession is regulated. Bob Michell fears that the veterinary profession will be
      affected, too.

PMID- 15715012
TI  - Out-of-hours cover.

PMID- 15715014
TI  - Old age problem?

PMID- 15715013
TI  - Effect of trace element supplementation on the fertility of dairy herds.

PMID- 15715016
TI  - New beginnings, fresh sounds...

PMID- 15715017
TI  - Posttraumatic stress disorder following preeclampsia and HELLP syndrome.
AB  - Posttraumatic stress disorder (PTSD) in connection with pregnancy was first
      described in the 1990s--initially in relation to childbirth but later more
      specifically to the mode of delivery. Instrumental vaginal delivery carries the
      highest risk of PTSD followed by emergency caesarean section and normal
      spontaneous delivery. Loss of pregnancy, spontaneous abortion or intrauterine
      death for example can also lead to PTSD. Little systematic research has been
      performed regarding the psychological consequences of severe preeclampsia or
      HELLP syndrome, although it would seem obvious that these conditions may have a
      great effect The combination of suffering a serious illness combined with an
      unexpected caesarean section or delivery, often of a premature child, is a heavy
      burden to bear both physically and psychologically. We describe here three
      patients who developed PTSD after pregnancies complicated by severe preeclampsia
      or HELLP syndrome. PTSD can develop after preeclampsia or HELLP syndrome.

PMID- 15715018
TI  - Measuring the ups and downs of pregnancy stress.
AB  - Despite substantial interest in the effects of stress on pregnancy, few
      instruments are available to measure pregnancy-specific stressors. Moreover,
      research has typically focused on the distressing, negative aspects of pregnancy.
      This report examines the reliability and validity of the Pregnancy Experience
      Scale (PES), a 41-item scale that measures pregnancy-specific daily hassles and
      uplifts. The PES was administered to two cohorts of low risk women at 24, 30, and
      36 weeks (n = 52) or 32 and 38 weeks (n = 137). Women perceived their pregnancies
      to be significantly more intensely and frequently uplifting than hassling.
      Internal scale reliability was high (alpha = 0.91 to 0.95). Frequency and
      intensity scores for hassles and uplifts were stable over time (r's = 0.56 to
      0.83) and patterns of convergent and discriminant validity emerged between the
      PES and existing measures of general affective intensity, daily stressors,
      depressive symptoms, and anxiety. These results indicate that (1) failure to
      measure pregnancy-specific stress will underestimate the degree to which pregnant
      women experience distress and (2) measurement of only the negative aspects of
      pregnancy will overestimate distress and fail to portray the degree to which
      women are psychologically elevated by their pregnancies. Measurement of hassles
      relative to uplifts may provide the most balanced assessment of pregnancy
      appraisal.

PMID- 15715019
TI  - Loneliness and pregnancy in an urban Latino community: associations with maternal
      age and unscheduled hospital utilization.
AB  - The objective is to compare loneliness in a pregnant population to a non-pregnant
      control group, and to evaluate loneliness and unscheduled hospital visits during
      pregnancy. A prospective cohort study in a Latino urban community including 53
      consecutive pregnant women in their first trimester, and 61 non-pregnant women as
      a control. The UCLA Loneliness Scale version 3, and demographic information was
      collected. A chart review after delivery determined total number of unscheduled
      pregnancy related hospital visits. Appropriate data analysis using t-test and
      regression analysis was used. Forty-eight women continued to delivery. There was
      no difference in mean loneliness scores between pregnant (41) and non-pregnant
      groups (43), or that of normal populations (41). There was a significant
      association between UCLA loneliness scores and total pregnancy related
      unscheduled hospital visits p = 0.042, beta = 0.06, r= 0.29. There was a
      significant association between increasing age and increasing loneliness during
      pregnancy p = 0.007, beta = 0.21, r= 0.36, not seen in the non-pregnant group p =
      0.98. Loneliness, when controlling for age, yielded a stronger association with
      unscheduled hospital visits p = 0.018, beta = 0.076, and r = 0.40. The findings
      were that increased loneliness is associated with increased unscheduled pregnancy
      related hospital utilization during pregnancy. Older pregnant women had higher
      loneliness scores. Loneliness was more significant than age in predicting higher
      unscheduled hospital visits. The combination of increased loneliness and younger
      age predicted the highest number of unscheduled hospital visits.

PMID- 15715020
TI  - Psychological well-being in women with Turner syndrome: somatic and social
      correlates.
AB  - Our aim was to examine possible somatic and social correlates to psychological
      well-being in adult women with Turner Syndrome (TS), including hormone
      replacement treatment Sixty-three women with a diagnosis of TS (mean age, 31.5
      years) participated in a cross-sectional study, using interview data, ratings on
      the Psychological General Well-being (PGWB) Index, and data from medical
      examinations and medical records. Statistical analysis was performed by bivariate
      and multivariate analyses. Lack of sex hormones during adult life and the
      presence of hearing impairment were related to lower psychological well-being, as
      were higher age at diagnosis, higher age at menarche or induced bleeding, higher
      chronological age and retrospectively reported difficulties with school subjects.
      Age at diagnosis and difficulties with school subjects explained 25% of the
      variation in psychological well-being. This study has identified some correlates
      to psychological well-being in women with TS, which are important when
      considering the clinical management of adult women with TS.

PMID- 15715021
TI  - Women's views of antidepressants in the treatment of postnatal depression.
AB  - Little research has been carried out on the treatment of postnatal depression and
      clinicians must currently rely on general recommendations for the use of
      antidepressants. Antidepressant medication as the main treatment for depression
      in general practice has been shown to be effective when used as prescribed.
      However, research has shown that depressed patients consistently receive either
      no medication or consistently low doses of medication. This study will
      investigate women's experiences of taking antidepressant medication for postnatal
      depression. Thirty-five women with a clinical diagnosis of postnatal depression
      who had been prescribed antidepressant medication completed a questionnaire
      detailing their experiences of taking medication. Four open-ended questions and
      responses were discussed with the women. Of the 35 women who were prescribed
      medication, 4 chose not to take it because they were breast-feeding. Twenty of
      the women described finding medication helpful. Although only 4 women directly
      reported not taking antidepressants as prescribed, the comments made by a further
      9 women suggest that compliance may have been poor. This study suggests a need to
      improve information about medication for postnatal depression. If this
      information is not provided, women are likely to continue to self-manage
      medication at a dosage that may be clinically ineffective.

PMID- 15715022
TI  - Self-report versus interview data of women's subjective theories of illness:
      concordance and predictive validity in a psychosomatic-gynecological liaison
      service.
AB  - Between-method comparisons of patient data from standardized self-report
      instruments and corresponding patient interview data frequently have poor
      agreement. We investigated the concordance and predictive validity of self-report
      measures and expert-rated interview data of women's subjective theories of
      illness in a psychosomatic-gynecological consultation liaison service. 31
      patients completed two questionnaires (KKG, PATEF) on subjective theories of
      illness and were interviewed with a semistructured instrument on the same topic
      at the time of the initial appointment and after 1.5 years. External criteria for
      assessing the predictive validity of questionnaire versus interview data were:
      follow-up participation and psychotherapy utilization during the follow-up
      interval. Questionnaire and interview rating data were only modestly associated.
      Rater concordance on the interview data was low. Neither the initial-assessment
      interview nor the questionnaire data had predictive validity for patients'
      participation in the follow-up. None of the interview rating data but a portion
      of the questionnaire data, had predictive validity for patients' utilization of
      psychotherapy during the follow-up interval. The cognitive conceptualization of
      subjective theories of illness may fail in patients with psychosomatic disorders,
      due to their very mode of experience. A wider approach that includes assessment
      of nonverbal communication and countertransference might be useful.

PMID- 15715023
TI  - Stress, social support, and emotional distress in a community sample of pregnant
      women.
AB  - Emotional distress in women during pregnancy has been shown to increase the risk
      of adverse outcomes for women and newborns. Increasingly, assessment and
      management of mood and anxiety problems during pregnancy entail consideration of
      life stress and interpersonal relationships with partners, friends, and family
      members. This study describes cross-sectional relations between life stress,
      perceived social support, and symptoms of depression and anxiety as well as the
      mediating influence of social support on relations between stress and symptoms. A
      community sample of women (N = 2,052) provided self-report data during their
      second trimester of pregnancy. Empirical fit was found for a structural equation
      model that depicted the combined influences of sociodemographic factors (i.e.,
      socioeconomic status, age, parity), stress (partner conflict and life events),
      and social support on symptoms of depression and anxiety, chi2 (df 51) = 310.65,
      p <.05; CFI=.91. Women who reported low levels of social support showed stronger
      relations between stress and symptoms than women who reported high levels of
      social support--indicative of a mediating effect of social support. Consistent
      with previous studies, results suggest that dyadic psychosocial assessment of
      pregnant women and their partners may facilitate interventions to augment support
      networks, thereby reducing the risk of emotional distress.

PMID- 15715024
TI  - Psychological difficulties within a group of patients with vulvodynia.
AB  - This study reviews and reports on some of the psychological difficulties seen in
      a group of women with vulval pain (vulvodynia). The investigation involved 164
      women (82 suffering with Vulvodynia and 82 women in a control group with general
      dermatology conditions) to establish the prevalence of psychological difficulties
      using validated questionnaires (SCL-90R and the IBQ) and reports on the possible
      effect these may have on sexual and relationship function and satisfaction. The
      level of psychological difficulties revealed significantly higher levels of
      psychological distress in the vulvodynia group within the domains of
      somatisation, obsessive-compulsive, depression, anxiety & phobic symptoms as well
      as with interpersonal sensitivity hostility and paranoia.

PMID- 15715025
TI  - Postnatal blues: a risk factor for postnatal depression.
AB  - Postnatal blues have been regarded as brief, benign and without clinical
      significance. However, several studies have proposed a link between blues and
      subsequent depression but have methodological problems. We report a prospective,
      controlled study of postpartum women with severe blues which uses systematically
      devised and validated instruments for that purpose which tests the hypothesis
      that severe blues increases the risk of depression in the six months following
      childbirth. 206 first-time mothers were recruited in late pregnancy. Blues status
      was defined using the Blues Questionnaire and those with severe blues and their
      controls who had no blues (matched for age, marital status and social class) were
      followed for 6 months with postal Edinburgh Postnatal Depression Scale. RDC
      diagnoses were made following SADS-L interview at the end of the protocol.
      Backwards stepwise Cox regression analysis found severe blues and past history of
      depression to be independent predictors each raising the risk by almost 3 times.
      Depression in those with severe blues onset sooner after delivery and lasted
      longer. The difference was largely accounted for by major depression. Severe
      postpartum blues are identified as an independent risk factor for subsequent
      postpartum depression. Screening and intervention programs could be devised.

PMID- 15715026
TI  - Psychological group support attenuates distress of waiting in couples scheduled
      for assisted reproduction.
AB  - The aim of the study is to determine whether a cognitive-behavioral group
      treatment could lead to a decrease of psychological distress in couples waiting
      for assisted reproduction. Fifty consecutive couples included in the waiting list
      for IVF-ET or ICSI were randomly allocated either to receive Cognitive-Behavioral
      Treatment (CBT Group) or just waiting (Observation Group). The group is formed by
      8-10 couples; 12 meetings are provided for a period of 4 months. Two psychometric
      test have been administered (Symptom Rating Test and Westbrook Coping Scales) at
      baseline and after 4 months. At baseline, females showed a higher level of SRT
      than males (F= 16.6+/-14.1; M = 10.2+/-9.0; p=0.01). This became evident for
      anxiety (F= 5.6+/-4.9; M =3.3+/-3.0, p = 0.004), somatization (F= 3.0+/-2.5; M =
      1.8+/-2.1, p = 0.01) and feelings of inadequacy (F = 3.9+/-3.7; M = 2.3+/-2.7, p
      = 0.01). After 4 months in the males of Observation Group (from 2.3+/-2.0 to
      4.0+/-2.8, p=0.01) there was an increase of the level of anxiety. No other
      meaningful differences in other variables were found. In females of CBT Group a
      trend towards a significant decrease in the total value of psychological
      uneasiness (the SRT) (from 17.7+/-13.7 to 14.1+/-14.0, p = 0.07) was found. A
      long wait before the scheduled intervention of assisted reproduction increased
      anxiety levels, namely in male partners. CBT avoids such a 'waiting stress' and
      could be useful for stimulating discussion and awareness inside the couple.
      Shortening the waiting list and psychological support would be provided by
      infertility centres

PMID- 15715027
TI  - Surface electromyography diagnostics in women with partial vaginismus with or
      without vulvar vestibulitis and in asymptomatic women.
AB  - The aim of this study was to investigate to what extent women with superficial
      dyspareunia can be diagnosed for both partial vaginismus (PaV) and vulvar
      vestibulitis (VVS) and to discover to what extent surface electromyography (sEMG)
      of the pelvic floor muscles (PFM) can distinguish between women with PaV solely,
      PaV+ VVS, and asymptomatic women. A total of 224 consecutive women with
      superficial dyspareunia were examined clinically for both PaV and VVS diagnoses.
      We examined 47 women with PaV+/-VVS and 27 asymptomatic women with sEMG of the
      PFM. The results showed that 102/224 women with superficial dyspareunia and 33/47
      women with PaV in the sEMG part of the study had both PaV and VVS. All women with
      VVS had vaginismus, while 42/224 had PaV but not VVS. sEMG measurements revealed
      no significant differences between the three groups of women (PaV solely, PaV +
      VVS, and asymptomatic). Almost half of the women with superficial dyspareunia
      referred to our clinic have both the diagnosis PaV and VVS. sEMG was not a method
      of any value to distinguish between women with PaV solely, PaV + VVS, or
      asymptomatic women. The increased tone found clinically in the PFM of women with
      PaV+/-VVS may be of other origin than electrogenic contractions.

PMID- 15715028
TI  - The illness experiences of women with fibroids: an exploratory qualitative study.
AB  - Previous research suggests that women attending gynaecology clinics experience
      high rates of psychological distress and psychiatric morbidity. Although the
      reasons for this are poorly understood, certain conditions appear to cause women
      particularly high levels of anxiety and depression. This paper reports a
      qualitative study, using Interpretative Phenomenological Analysis (IPA), to
      examine the illness experiences of women with the common gynaecological condition
      of fibroids. The study employs semi-structured interviews, guided by Leventhal's
      self-regulation model, to explore 18 women's understanding and experiences of
      having fibroids. Qualitative analysis revealed eight themes drawn into two higher
      order themes - 'Managing uncertainty' and 'Struggling between defeat and
      optimism'. These higher-order themes illustrate the multiplicity of experiences
      and meanings used by women attempting to understand their condition, treatment
      options and future health outcomes. The differences in women's illness
      representations may account for differences in their relative distress levels.
      The findings indicate the importance of considering an individual's illness
      representations in order to facilitate the provision of appropriate medical and
      psychological care to women with fibroids.

PMID- 15715029
TI  - Further psychometric testing of a brief personality scale to measure
      vulnerability to postpartum depression.
AB  - The Vulnerability Personality Style Questionaire (VPSQ), a 9-item self-report
      personality scale, was developed to identify women at-risk for postpartum
      depression due to personality vulnerability. Preliminary research with this scale
      suggests it has satisfactory psychometric properties. The purpose of this
      methodological study was to further examine the psychometric properties of the
      VPSQ in a sample of Canadian women. As part of a longitudinal study, women
      completed postal questionnaires at 1, 4, and 8 weeks postpartum that included the
      VPSQ, Edinburgh Postnatal Depression Scale, Rosenburg Self-Esteem Scale, and
      Perceived Stress Scale. Five hundred and ninety-four women returned
      questionnaires suitable for analysis. The Cronbach's alpha coefficient for the
      VPSQ was 0.67 and significant correlations between the VPSQ and self-esteem (r =
      0.58) and perceived stress (r = 0.55) scales were found, providing evidence for
      construct validity. In a logistic regression analysis, VPSQ was predictive of
      developing depressive symptomatology 1, 4 and 8 weeks postpartum; an increase of
      one point on the VPSQ increased the risk of developing postpartum depression 1.3
      fold. The results from this study support the overall utility of the VPSQ. As
      such, this brief instrument is ready to assist in the identification of women at
      risk of developing postpartum depression such that appropriate secondary
      preventive or treatment interventions may be initiated.

PMID- 15715030
TI  - Cancer: a reproductive strategy of "ultra-selfish" genes?
AB  - A hypothesis is presented in which the process of "malignant transformation"
      which ultimately results in the rapidly dividing tumor(s)(cells) causing
      "cancer", is regarded as an evolved reproductive strategy of "ultra-selfish"
      (proto-)(onco-) genes, already present in the genome, or introduced by a virus.

PMID- 15715031
TI  - Self management: a new paradigm in patient education?

PMID- 15715032
TI  - Implications of coping repertoire as predictors of men's stress, anxiety and
      depression following pregnancy, childbirth and miscarriage: a longitudinal study.
AB  - The long-term implication of how men cope during a partner's pregnancy, at
      childbirth or following miscarriage has not received attention. This study aims
      to examine if men's coping response during pregnancy, at childbirth, or
      miscarriage predict psychological outcomes at the time of childbirth/miscarriage
      or 1 year later, and to establish whether there are any changes in men's coping
      repertoire. Utilizing a longitudinal design, 384 volunteer expectant fathers,
      participated by completing measures of stress, anxiety, depression and coping
      during their partner's pregnancy, following childbirth or miscarriage, and 1 year
      later. Findings indicated, at the time of childbirth/miscarriage, increases on
      all psychological outcomes compared to during the pregnancy, which then decreased
      at 1-year. During pregnancy, men relied more on approach-orientated coping,
      changing at pregnancy outcome to avoidant-orientated strategies. Regression
      revealed the best predictor of psychological outcome, in the long-term, was
      coping response at pregnancy outcome. However each psychological outcome had its
      own predictive path, varying depending on pregnancy outcome; supporting the
      concept that coping responses are situationally specific, changing depending on
      the event examined. How men cope with each aspect of their reproductive
      experiences may have implications for the provision of support they offer their
      partner, and the support they themselves need.

PMID- 15715033
TI  - Couples becoming parents: something special after IVF?
AB  - The majority of catamnestic studies on successful IVF treatment deal with the
      development of the children and the parent-child-relationship. Far fewer studies
      pay attention to the changes within the relationship of couples that become
      parents. This particular study focused on the transition from partnership to
      parenthood with assessments at different measuring points (T1: the last trimester
      of pregnancy; T2: 3 months after birth; and T3: 12 months after birth) and
      compared 47 IVF couples with 45 couples that conceived naturally. The couples
      were observed with psychodynamic couple interviews and standardized as well as
      non-standardized questionnaires. The most striking result of our study was the
      inconspicuousness of IVF couples and their parent-child-relationship.
      Partnerships featured a high degree of satisfaction among the couples; the
      progress of pregnancy was described as very satisfying and free of complaints.
      Surprisingly these descriptions were given despite more frequent and longer
      hospital stays by the IVF women during their pregnancy. However, IVF couples
      acted less openly in the interviews and expressed their own feelings less often,
      especially the more negative ones. In the partnerships we found that IVF women
      displayed more avoiding tendencies in their relationships 1 year after the birth
      of their child/children.

PMID- 15715034
TI  - Massage therapy effects on depressed pregnant women.
AB  - Eighty-four depressed pregnant women were recruited during the second trimester
      of pregnancy and randomly assigned to a massage therapy group, a progressive
      muscle relaxation group or a control group that received standard prenatal care
      alone. These groups were compared to each other and to a non-depressed group at
      the end of pregnancy. The massage therapy group participants received two 20 min
      therapy sessions by their significant others each week for 16 weeks of pregnancy,
      starting during the second trimester. The relaxation group provided themselves
      with progressive muscle relaxation sessions on the same time schedule.
      Immediately after the massage therapy sessions on the first and last days of the
      16-week period the women reported lower levels of anxiety and depressed mood and
      less leg and back pain. By the end of the study the massage group had higher
      dopamine and serotonin levels and lower levels of cortisol and norepinephrine.
      These changes may have contributed to the reduced fetal activity and the better
      neonatal outcome for the massage group (i.e. lesser incidence of prematurity and
      low birthweight), as well as their better performance on the Brazelton Neonatal
      Behavior Assessment. The data suggest that depressed pregnant women and their
      offspring can benefit from massage therapy.

PMID- 15715035
TI  - The impact of endometriosis upon quality of life: a qualitative analysis.
AB  - OBJECTIVE: to explore and describe the impact of endometriosis upon quality of
      life. SETTING: Nuffield Department of Obstetrics and Gynaecology, University of
      Oxford. DESIGN: qualitative study. SAMPLE: twenty-four women with a laparoscopic
      diagnosis of endometriosis. METHODS: face to face, individual, in-depth
      interviews. RESULTS: analysis of the data revealed 15 descriptive categories.
      Pain, physical functioning, role performance, social functioning, emotional well
      being, relationship with the medical profession, treatment, sexual intercourse,
      energy and vitality, employment and infertility were found to be a particular
      concern for women with endometriosis. Physical appearance, lack of control and
      powerlessness, feelings of social isolation and concerns that their daughters
      might develop endometriosis were new areas found to be negatively affected by the
      condition. CONCLUSIONS: the impact of endometriosis-associated symptoms upon
      quality of life is multidimensional and more complex than just negatively
      affecting psychosocial parameters. Conducting in-depth interviews to explore the
      subjective experiences of patients with endometriosis enabled the diverse areas
      of quality of life to be identified. Adopting a qualitative methodology is
      essential for item generation on disease specific health status questionnaires.

PMID- 15715036
TI  - Reactions and reflections in men, 4 and 12 months post-abortion.
AB  - BACKGROUND: in general, men involved in legal abortion constitute an invisible
      group and there is scarcely any knowledge about their experiences and opinions.
      Therefore, the aim of the present study was to increase knowledge about reactions
      and reflections by means of a prospective study of men's attitudes and feelings
      towards abortion. METHODS: twenty-six men answered a questionnaire before
      abortion, and participated in interviews at the time of abortion and 4 and 12
      months post-abortion. RESULTS: nearly all of the men were happy with the women's
      decision to have an abortion at both follow-ups. They experienced the abortion as
      a relief and a responsible act. Simultaneously, abortion could also be
      experienced as a painful and ethically problematic act. Overall, most men had
      only positive experiences post- abortion, such as a feeling of maturity. More
      than half of those who accompanied their partners to the hospital felt that the
      staff did not have a welcoming attitude. It was also found that 1-year post
      abortion, more than a third consistently did not use a reliable contraceptive
      method. CONCLUSIONS: there is a need for further studies concerning men's
      experiences and reactions in the context of abortion and it is of fundamental
      importance that a gender perspective is incorporated into this specific field of
      reproductive health research.

PMID- 15715037
TI  - Anonymous oocyte donation: a follow-up analysis of donors' experiences.
AB  - BACKGROUND: this study was conducted to assess oocyte donors' satisfaction after
      the procedure and to obtain information on base rates of various experiences
      associated with oocyte donation. METHODS: volunteer anonymous oocyte donors seen
      at a university-based IVF programs were identified (N = 54). The follow-up
      questionnaire asked donors to rate aspects of clinic interactions, medical
      procedures and experiences during and after the process, as well as expectations
      and level of fulfillment. RESULTS: ten individuals were lost to follow-up and 20
      donors did not respond. The typical oocyte donor respondent (N = 24) was 26.5
      years old, Caucasian, single with no children and had experienced some college
      education. Mean follow-up time was 21 months. Overall, 79% were satisfied or
      extremely satisfied with their experience, 42 % would be an oocyte donor again
      and 50% would recommend that a friend consider being an oocyte donor. Donors
      tolerated procedures well, but most did experience cramping and injection site
      pain. A significant proportion experienced anxiety and negative emotional
      experiences during the process. Expectations were fulfilled regarding helping
      another woman and sense of satisfaction, but most (87.5%) expressed the desire to
      know the outcome for the recipient. CONCLUSIONS: the data demonstrate that oocyte
      donation was a positive experience for the majority of women in the program,
      although emotional symptoms are normative.

PMID- 15715038
TI  - MRI of female genital and pelvic organs during sexual arousal.
AB  - We utilized contrast enhanced magnetic resonance imaging (MRI) to delineate the
      anatomy of the female genital and pelvic organs during sexual arousal. Eleven
      healthy pre-menopausal women and eight healthy post-menopausal women underwent
      MRI of the pelvis while watching an erotic video. A 1.5 Tesla MR system was used
      to produce T1-weighted images following administration of MS-325, a gadolinium
      based blood pool contrast agent. Selected structural dimensions and enhancement
      were measured prior to and during sexual arousal. In both pre- and post
      menopausal subjects, vestibular bulb and labia minora width increased with
      arousal. Enhancement measurements increased in the bulb, labia minora and
      clitoris in both pre- and post-menopausal subjects, and in the vagina in pre
      menopausal subjects. There were no marked changes in size or enhancement of the
      labia majora, urethra, cervix, or rectum during sexual arousal in pre- or post
      menopausal subjects. Using MRI, we observed specific changes in the female
      genitalia and pelvic organs with sexual arousal, in both pre- and post-menopausal
      women. MRI can potentially provide detailed anatomical information in the
      assessment of female sexual function, particularly with regard to changes in
      blood flow.

PMID- 15715039
TI  - Grief after termination of pregnancy due to fetal malformation.
AB  - Termination of pregnancy for fetal malformation is a traumatic event which any
      woman finds hard to withstand and which entails the risk of severe and
      complicated grieving. This paper presents three cases illustrating the trauma and
      coping mechanisms. Grieving continued for over 6 months in all cases and included
      pathological anxiety and depression. We offer advice and counselling to such
      women.

PMID- 15715040
TI  - Deceive, and be deceived!
AB  - In their struggle for life, many species, for example prokaryotes, plants and
      animals, defend themselves by producing substances which may poison or
      disorientate (potential) enemies (grazers/predators etc), or signal information
      which puts (potential) enemies on the wrong track. Examples of poisonous/
      disorientating substances include prussic acid (e.g. almonds) or morphine
      (papaver), examples of 'false' visual cues include the appearance of harmless
      hoverflies which strongly resemble 'dangerous' wasps or certain orchid flowers
      which resemble the female sex organs of certain insects ('mimicry'). Misleading
      is an essential part of communication systems.

PMID- 15715041
TI  - Quantitative analysis of inflammatory and immune responses in dogs with gastritis
      and their relationship to Helicobacter spp. infection.
AB  - The present study sought to quantitatively examine mucosal inflammatory and
      immune responses in dogs with gastritis and the relationship of these responses
      to infection with Helicobacter. Gastric biopsies from 30 dogs were evaluated for
      B- and T-lymphocytes, neutrophils, eosinophils, macrophages, and mast cells.
      Mucosal atrophy, fibrosis, cellularity, and severity of gastritis were graded
      qualitatively. Messenger-RNA (mRNA) for actin, interleukin-1beta (IL-1beta), IL
      4, IL-8, and IL-10, transforming growth factor beta (TGF-beta), and interferon
      gamma (IFN-gamma) was quantified by polymerase chain reaction (PCR). The presence
      of Helicobacter spp. was determined by urease activity, histology, PCR, and
      enzyme-linked immunosorbent assay. mRNA for IL-1beta, IL-8, IL-10, TGF-beta, and
      IFN-gamma was detected in most dogs. IL-4 mRNA was detected in only 1 dog.
      Correlations were observed for IL-1beta versus IL-8 and IL-10; IL-8 versus IL-10,
      IFN-gamma, and TGF-beta; and IL-10 versus IFN-y. Mucosal pathology was related to
      cytokine mRNA expression (neutrophils to IL-8 and IFN-gamma, macrophages and
      lymphocytes to IFN-gamma, and fibrosis to IL-1beta). Gastritis was categorized as
      lymphoplasmacytic in all dogs, and its histologic severity correlated with
      atrophy, infiltration with lymphocytes and macrophages, and expression of IL-10
      and IFN-gamma. Of the dogs examined, 76.7% were infected with Helicobacter spp.
      Infection was associated with increased expression of TGF-beta and fibrosis.
      Circulating anti-Helicobacter immunoglobulin G titers were higher in uninfected
      than infected dogs. We conclude that lymphoplasmacytic gastritis in dogs is
      characterized by concurrent activation of proinflammatory and immunomodulatory
      cytokines, with increased mRNA expression related to mucosal pathology. No
      significant associations between Helicobacter infection and proinflammatory
      cytokine expression, severity of gastritis, or differences in the pathogenicity
      of different Helicobacter spp. were found.

PMID- 15715042
TI  - Comparison of ultrasonography, computed tomography, and single-photon emission
      computed tomography for the detection and localization of canine insulinoma.
AB  - Accurate preoperative detection, localization, and staging of the primary tumor
      and metastases are essential for the selection of appropriate candidates for
      surgery. In dogs with insulinoma, preoperative assessment usually is performed
      with transabdominal ultrasonography (US). There are no reports on the use of
      computed tomography (CT) for this purpose. The preoperative use of somatostatin
      receptor scintigraphy (SRS) recently has been advocated for the identification of
      insulinoma and gastrinoma in dogs, but its accuracy remains to be established. In
      this report US, CT, and single-photon emission computed tomography (SPECT) with
      [111In-DTPA-D-Phe1]-octreotide (a specific form of SRS) were compared for their
      effectiveness in detecting and localizing primary and metastatic insulinoma in
      dogs. Findings at surgery or postmortem examination served as control. Of 14
      primary insulinomas, 5, 10, and 6 were correctly identified by US, CT, and SPECT,
      respectively. No lymph node metastases were detected by US or SPECT. CT
      identified 2 of 5 lymph node metastases but also identified 28 false-positive
      lesions. Two of 4 livers were found to be positive for metastases by 1 of the
      imaging techniques. US can be used for the initial evaluation of dogs with
      hypoglycemia. Although CT identifies most primary tumors, intraoperative
      inspection and palpation of the pancreas is still superior. SPECT appears as
      effective as US and CT in detecting insulinomas. Future developments in
      preoperative imaging techniques might improve current methods of canine
      insulinoma detection.

PMID- 15715043
TI  - Plasma pro-opiomelanocortin, pro-adrenocorticotropin hormone, and pituitary
      adenoma size in dogs with Cushing's disease.
AB  - It is difficult to predict the size of pituitary corticotroph tumors in dogs with
      Cushing's disease (pituitary-dependent hyperadrenocorticism [PDH]) without
      pituitary imaging techniques. The purpose of this study was to examine the
      relationship between plasma adrenocorticotropin hormone (ACTH) precursor
      concentration and pituitary size in dogs with Cushing's disease. Plasma
      concentrations of ACTH precursors (pro-opiomelanocortin [POMC]/pro-ACTH) and
      pituitary tumor height/brain area were measured in 36 dogs with pituitary
      corticotroph adenomas of various sizes. There was a correlation between tumor
      size (measured as the pituitary tumor height/brain area ratio [P/B]) and POMC/pro
      ACTH concentration (r = .70; P < .0001). Dogs with P/B > or = 0.40 x 10(-2) mm(
      1) had higher concentrations of ACTH precursors than dogs with P/B < 0.40 x 10(
      2) mm(-1) (median concentration 85 pmol/L, range 15-1,350 pmol/L, n = 14 versus
      15 pmol/L, range 15-108 pmol/L, n = 22; P < .0001). With a threshold of 35 pmol/L
      of POMC/pro-ACTH concentration, the estimated sensitivity and specificity of the
      kit were 93% (95% confidence interval [CI], 79-100%) and 86% (95% CI, 73-100%),
      respectively. We interpret these data as indicating that measurement of POMC and
      pro-ACTH might be of value in the characterization of tumor size in dogs with
      Cushing's disease. Low POMC/pro-ACTH concentrations make it unlikely that a large
      pituitary tumor exists in dogs with PDH.

PMID- 15715044
TI  - Uses and effectiveness of pamidronate disodium for treatment of dogs and cats
      with hypercalcemia.
AB  - Uncorrected hypercalcemia can cause clinical signs such as polyuria, polydipsia,
      vomiting, diarrhea, lethargy, and depression and contributes to the development
      of primary renal failure and soft tissue mineralization. Treatment of
      hypercalcemia includes diagnosis and treatment of the underlying disease process
      and some combination of excracellular fluid volume expansion by administration of
      fluids intravenously and administration of glococorticosteroids, salmon
      calcitonin, and furosemide. Bisphosphonates such as pamidronate disodium also may
      be safe and effective in the treatment of hypercalcemia. The purpose of our study
      was to characterize the efficacy and safety of pamidronate in the treatment of
      hypercalcemia attritutable to several different disease processes in the dog and
      cat. Seven dogs and 2 cats were administered pamidronate at a dose of 1.05-2.0
      mg/kg IV for a variety of disease processes, including neoplasia (n = 4),
      calcipotriene toxicity (n = 3), nocardiosis (n = 1), and idiopathic hypercalcemia
      with chronic renal failure (n = 1). In all the animals, IV pamidronate
      administration rapidly decreased serum calcium concentrations without evident
      toxicosis. Two animals received pamidronate several times without obvious
      toxicosis. On the basis of the findings in our retrospective study, pamidronate
      may be a safe and effective drug with which to lower both serum total and ionized
      calcium concentrations in patients with hypercalcemia arising from a wide variety
      of underlying disease processes.

PMID- 15715045
TI  - Sustained strenuous exercise increases intestinal permeability in racing Alaskan
      sled dogs.
AB  - We assessed gastric and intestinal permeability and performed gastroscopy to
      evaluate the effects of sustained strenuous exercise on the gastrointestinal
      tract in racing sled dogs. Three teams of racing Alaskan sled dogs were examined
      approximately 1 week before and 24 hours after the 2003 Iditarod sled dog race
      (1,100 miles in 10 days). Each examination consisted of the administration of a
      solution of sucrose, lactulose, and rhamnose to evaluate gastric and intestinal
      permeability, as well as gastroscopy to visually inspect the gastric mucosa. Of
      the 54 dogs examined before the race, 16 completed the course and contributed
      data to the analysis. Sustained strenuous exercise was associated with an
      increased frequency of gastric erosions or ulcerations seen endoscopically (0%
      prerace versus 61% postrace). A significant postrace increase occurred in the
      median lactulose to rhamnose ratio in both serum and urine (0.11 versus 0.165, P
      = .0363; 0.11 versus 0.165, P = .0090, respectively). No significant differences
      were found in median serum or urinary sucrose concentrations when pre- and
      postrace values were compared. No correlation was found between visible gastric
      lesions and the concentration of sucrose in serum or urine samples obtained 4-5
      hours after administration of the sugar solutions. We conclude that sustained
      strenuous exercise is associated with increased intestinal permeability, but the
      sucrose permeability test as we performed it did not correlate with visible
      gastric lesions.

PMID- 15715046
TI  - Improvement in liver pathology after 4 months of D-penicillamine in 5 doberman
      pinschers with subclinical hepatitis.
AB  - Five female Doberman Pinschers with increased hepatic copper concentrations and
      persistent (3-4 years) subclinical hepatitis were treated with D-penicillamine
      for 4 months. Before and after treatment, the dogs underwent clinical,
      hematologic (red blood cell, white blood cell, and differential and thrombocyte
      counts), and clinical chemistry (creatinine, alkaline phosphatase, alanine
      aminotransferase, and total bile acid concentrations) examinations, and liver
      biopsies were examined histologically and their copper content measured
      quantitatively. No adverse effects were observed during treatment, and CBC and
      serum chemistry test results did not change. The mean liver copper concentration
      was 1,036 mg/kg dry matter before treatment and decreased to 407 mg/kg after
      treatment (P = .03). The copper concentrations had decreased (by between 134 and
      1,135 mg/kg dry matter) in all of the dogs. The histopathologic appearance had
      improved or returned to normal in all 5 dogs. We conclude that D-penicillamine
      effectively reduced copper retention in these dogs and improved the
      histopathologic appearance of the lesions. However, because D-penicillamine has
      both copper-chelating and anti-inflammatory properties, it is not possible to
      draw conclusions on the etiology of this disease.

PMID- 15715047
TI  - A variant form of neuronal ceroid lipofuscinosis in American bulldogs.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases
      characterized by accumulations of autofluorescent lipopigments within cells of
      the nervous system. Nine related American Bulldogs demonstrated dysmetria in all
      limbs and paraparesis. Nonambulatory tetraparesis was observed only in the later
      stages of the disease. The clinical signs developed between 1 and 3 years of age
      and were slowly progressive over several years, which is inconsistent with most
      reports in other breeds. Results from blood tests for 8 different lysosomal
      storage diseases on 4 affected and 6 related but unaffected dogs were negative.
      Four affected dogs were euthanized and histopathologic examinations showed
      diffuse accumulations of periodic acid-Schiff-positive inclusions in neurons and
      axonal spheroids along the entire neuraxis and retinae. The most severe lesions
      were in the brainstem proprioceptive nuclei and spinal cord, consistent with
      clinical signs. The storage material was autofluorescent and
      immunohistochemically positive for products of lipid peroxidation.
      Ultrastructural analysis was consistent with NCL. Pedigree analysis supports an
      autosomal-recessive mode of inheritance. NCL has not been previously reported in
      the American Bulldog and these findings suggest a variant form of the canine
      disease.

PMID- 15715048
TI  - Clinical characteristics of mammary carcinoma in male cats.
AB  - There is little information regarding mammary tumors in male cats. The purpose of
      this study was to characterize the clinical characteristics of mammary carcinoma
      in male cats, compare this malignancy to the disease in female cats, and identify
      prognostic factors. Thirty-nine male cats with mammary carcinoma were identified.
      One pathologist reviewed the biopsies from all cats, and complete follow-up
      information regarding outcome was available for 27 cats. Information collected
      included signalment, age at neutering, history of progestin therapy, age at tumor
      diagnosis, size of tumor, type of surgery (lumpectomy, simple mastectomy, or
      radical mastectomy), results of clinical staging, adjunctive therapies, time to
      local recurrence, survival, and cause of death. The mean age at tumor diagnosis
      (12.8 years) was slightly older than that reported in female cats. The incidence
      of local tumor recurrence in 9 of 20 (45%) cats was similar to that reported in
      females. A history of progestin therapy was present in 8 of 22 (36%) cats for
      which this information was known. The median time to local recurrence was 310
      days (range 127-1,363 days), and overall median survival was 344 days (range 14
      2,135 days). Tumor size and lymphatic invasion were identified as negative
      prognostic factors. This study indicates that mammary carcinoma in the male cat
      has many similarities to the disease in females, with an aggressive clinical
      course in most cats.

PMID- 15715050
TI  - Clinical, biochemical, and hematological characteristics, disease prevalence, and
      prognosis of dogs presenting with neutrophil cytoplasmic toxicity.
AB  - Neutrophil cytoplasmic toxicity is manifested as an abnormality in cell size or
      the cytoplasmic content upon examination of Romanowsky-stained blood smears, and
      is traditionally associated with infection and inflammation. The purpose of this
      retrospective study was to investigate the association of such changes with
      clinical and clinicopathologic characteristics, diseases, and prognoses in dogs.
      Dogs with neutrophil toxicity (n = 248) were compared with negative controls (n =
      248). Statistical analyses included chi-square tests, independent t-tests,
      nonparametric Mann-Whitney tests, the chi-square trend test, and survival
      analysis. Dogs with neutrophil toxicity had a significantly higher prevalence of
      pale mucous membranes, tachycardia, fever, abdominal organomegaly, icterus,
      melena, and hematuria. Most mean hematologic variables were significantly
      different between groups. Dogs with neutrophil toxicity had a significantly (P <
      .05) higher prevalence of leukocytosis, leukopenia, neutrophilia, neutropenia,
      anemia, hyponatremia, hypokalemia, hypoproteinemia, hypoalbuminemia, and
      hypocalcemia. The prevalence of pyometra, parvovirus infection, acute renal
      failure, peritonitis, immune-mediated hemolytic anemia, disseminated
      intravascular coagulation, pancreatitis, septicemia, and neoplastic disorders was
      significantly higher among these dogs. Case fatality, hospitalization length, and
      treatment cost were significantly (P < .001) higher in dogs with neutrophil
      toxicity. Neutrophil toxicity severity was significantly (P < .0035) and
      positively associated with neutropenia, and negatively associated with
      leukocytosis and neutrophilia. A significant trend (P = .05) toward increasing
      case fatality with an increase of neutrophil toxicity was observed. In the
      neutrophil toxicity group, dogs with leukopenia (<5.0 X 10(3)/mm3) had a
      significantly (P < .0001) higher case fatality compared to dogs with normal or
      high leukocyte counts. We conclude that evaluation of blood smears for neutrophil
      cytoplasmic toxicity provides useful clinical information and can serve as a good
      prognostic predictor.

PMID- 15715049
TI  - Bone marrow-derived dendritic cell vaccination of dogs with naturally occurring
      melanoma by using human gp100 antigen.
AB  - Canine malignant melanoma (CMM) is a common and aggressive form of cancer in
      dogs. Established therapeutic approaches such as surgery, chemotherapy, and
      radiation therapy (RT) have not proven curative. As a coadjuvant of RT and to
      enhance the antimelanoma immune response, we characterized dendritic cells (DCs)
      from the bone marrow (BM) of dogs with CMM, ex vivo, for use in therapeutic
      vaccines. BM mononuclear cells from 3 dogs with melanoma and from 1 healthy dog
      were cultured for 12 days in media supplemented with recombinant human
      granulocyte-macrophage colony stimulating factor, stem cell factor, tumor
      necrosis factor, and Flt-3 ligand. On day 11, DCs were transduced with an
      adenovirus vector encoding a xenoantigen, human melanoma antigen gp100. Each dog
      received 3 subcutaneous vaccinations over a 4-month period. Phenotypic analysis
      of the expanded DC population demonstrated expression of CD11c/CD18 and major
      histocompatibility complex class II surface markers, and ultrastructural features
      characteristic of DCs were observed on electron microscopy. On functional
      analysis, these DCs were able to stimulate allo-reactivity and capture and
      express gp100. One dog demonstrated antigen-specific cytotoxic T lymphocyte (CTL)
      activity in peripheral blood lymphocytes. This dog has displayed no clinical
      signs, either locally or systemically, of recurrent melanoma 48 months after
      initial DC injection. However, another dog, which was CTL negative, relapsed 22
      months after vaccination. Ex vivo DC expansion is feasible for immunotherapy of
      spontaneous cancers in outbred dogs.

PMID- 15715051
TI  - Evaluation of intravenous pamidronate administration in 33 cancer-bearing dogs
      with primary or secondary bone involvement.
AB  - The purpose of this study was to evaluate the clinical safety of pamidronate when
      administered at a mean dosage of 1.0 mg/kg IV q28d in 33 tumor-bearing dogs.
      Biochemical tests of renal function were evaluated before each successive
      pamidronate treatment. Of 33 dogs treated with pamidronate, 1 dog had clinically
      relevant increases in serum creatinine and blood urea nitrogen concentrations.
      The biologic activity of IV pamidronate was assessed prospectively in 10 dogs
      with appendicular osteosarcoma and was assessed on reductions in urine N
      telopeptide excretion (P = .042) and enhanced bone mineral density of the primary
      tumor measured with dual-energy x-ray absorptiometry (P = .024). Additionally, in
      these 10 dogs, pamidronate's therapeutic activity was supported by subjective
      improvement in pain control in 4 of the 10 dogs treated. IV pamidronate appears
      clinically safe in tumor-bearing dogs and may possess modest biologic activity
      for managing neoplastic complications associated with pathologic bone resorption.

PMID- 15715052
TI  - Clinical evaluation of gemcitabine in dogs with spontaneously occurring
      malignancies.
AB  - We conducted a clinical evaluation of gemcitabine in 19 dogs with spontaneously
      occurring malignancies. The principal objectives of this study were to
      characterize toxicity and seek preliminary evidence of antitumor activity of
      gemcitabine administered every 2 weeks (biweekly) as a 30-minute IV infusion. A
      total of 64 doses, ranging from 300 mg/m2 to 675 mg/m2, were administered during
      the initial 8-week evaluation period, and an additional 131 doses were
      administered during the extended evaluation period. The total cumulative dose for
      the 10 dogs receiving gemcitabine in the extended evaluation period ranged from
      1,500 mg/m2 to 24,300 mg/m2. Clinical evidence of toxicity was minimal.
      Cumulative myelosuppression was not apparent. Unexplained retinal hemorrhages
      occurred in 1 dog. No complete or partial remissions were observed during the
      initial evaluation period; however, objective responses were observed in 2 dogs
      during the extended evaluation period. Gemcitabine is a promising new
      chemotherapeutic agent that can be used safely in dogs with cancer. Biweekly
      administration of doses of 675 mg/m2 IV results in minimal and acceptable
      toxicity.

PMID- 15715053
TI  - Effect of airway disease on blood gas exchange in racehorses.
AB  - Inflammatory Airway Disease (IAD), exercise-induced pulmonary hemorrhage (EIPH),
      and upper airway obstruction (UAO) are common respiratory tract diseases that can
      decrease performance. The purpose of this retrospective study was to compare
      bronchoalveolar lavage fluid cytology and arterial blood gas analysis during a
      treadmill test by poorly performing racehorses presented to Purdue University.
      One hundred thirty-two horses with a history of poor performance were included in
      this study. Ten horses with no history or diagnosis of EIPH, IAD, or UAO served
      as controls. Horses were evaluated by rhinolaryngoscopy for upper airway
      abnormalities and underwent a standardized treadmill test, and samples were
      collected for blood gas analysis. Horses with IAD or EIPH had a more severe
      exercise-induced hypoxemia, (mean+/-SD; 84.8+/-1.5 and 86.0+/-1.7 mm Hg average
      Pao2, respectively), than horses in the control group (92.8+/-2.1 mm Hg). The
      average Pao2 of horses with only UAO (88.3+/-3.3 mm Hg) was not significantly
      different from control horses. Gas exchanges were the most severely impaired in
      horses affected with both EIPH and UAO because they exhibited the lowest Pao2 and
      highest Paco2 values (66.5+/-15.2 and 52.2+/-6.3 mm Hg, respectively).

PMID- 15715054
TI  - Measurement of serum IgG in foals by radial immunodiffusion and automated
      turbidimetric immunoassay.
AB  - Hypogammaglobulinemia as a result of failure of transfer of passive immunity
      (FTPI) is an important risk factor for infectious disease in neonatal foals. The
      current gold standard for determining serum immunoglobulin concentrations is
      radial immunodiffusion (RID). The purpose of this study was to compare
      immunoglobulin concentrations measured by RID with those determined by an
      automated turbidimetric immunoassay (TIA), which has a much shorter turnaround
      time. Immunoglobulin concentrations were measured by both RID and TIA in serum
      collected from 84 neonatal foals. Sixty-seven foals had results within the linear
      range for both assays. Sensitivity and specificity of TIA for diagnosis of FTPI
      with IgG < or = 800 mg/dL were 0.81 (95% CI 0.70-0.88) and 0.86 (95% CI 0.76
      0.93) and with IgG < or = 400 mg/dL were 0.63 (95% CI 0.35-0.86) and 0.92 (95% CI
      0.87-0.95), respectively. A significant linear relationship was found between IgG
      concentrations determined by TIA and RID (TIA = 0.9511RID + 8.4354; R2 = .59, P <
      .0001). The coefficients of variation for between-run and within-run precision
      for the TIA were 2.5 and 3%, respectively. Storage of samples from 10 foals at 
      20 degrees C for 10-12 months resulted in a reduction in TIA-measured serum IgG
      concentration of -17.6% (SD = 3.7%), indicating that long-term storage of samples
      at -20 degrees C should be avoided. The results of this study indicate that
      measurement of serum IgG by TIA can be used to evaluate foals for FTPI.

PMID- 15715055
TI  - Effect of suckling cow's milk or milk replacer on abomasal luminal pH in dairy
      calves.
AB  - Abomasal ulceration occurs commonly in suckling calves, and the cause for the
      high prevalence of abomasal ulceration is unknown. We hypothesized that diet may
      play a role in the etiopathogenesis of abomasal ulceration. Six male dairy calves
      with an abomasal body cannula suckled fresh Holstein cow's milk, all milk-protein
      milk replacer, or combined milk- and soy-protein milk replacer twice daily at 12%
      of body weight/d. Abomasal luminal pH was measured every second for 24 hours by
      using a miniature glass pH electrode. Mean 24-hour abomasal luminal pH for all
      milk-protein milk replacer (3.22) and combined milk- and soy-protein milk
      replacer (3.27) were similar but significantly (P < .05) higher than that for
      cow's milk (2.77; standard error = 0.08). Both milk-replacer formulations failed
      to clot after the addition of chymosin, whereas cow's milk clotted within 2
      minutes. The in vitro titration curve of cow's milk and all milk-protein milk
      replacer were similar, but different to that of combined milk- and soy-protein
      milk replacer. The osmolalities of all milk-protein milk replacer (375 mOsm/kg)
      and combined milk- and soy-protein milk replacer (410 mOsm/kg) were greater than
      that of cow's milk (278 mOsm/kg). The slightly lower mean abomasal luminal pH in
      calves suckling cow's milk, compared to milk replacer, was probably due to
      clotting of cow's milk, with extrusion of low pH whey, and a slower rate of
      abomasal emptying caused by the hyperosmolality of milk replacer. Examination of
      our results suggests that suckling cow's milk may increase the prevalence of
      abomasal ulceration by decreasing mean luminal pH, although this remains to be
      determined.

PMID- 15715056
TI  - Dynamic cervical lung hernia in a dog with chronic airway disease.

PMID- 15715057
TI  - D-lactic acidosis secondary to exocrine pancreatic insufficiency in a cat.

PMID- 15715058
TI  - Chronic intestinal pseudo-obstruction in a cat caused by visceral myopathy.

PMID- 15715059
TI  - Urinary tract manifestations of protothecosis in dogs.
AB  - Records of 13 dogs with systemic infection with Prototheca sp. from 3 veterinary
      teaching hospitals were reviewed. Acute renal failure secondary to disseminated
      infection with Prototheca zopfii was diagnosed in 2 dogs. In 1 dog, acute renal
      failure developed during administration of immunosuppressive drugs for treatment
      of anterior uveitis. During diagnostic evaluation of this dog, Prototheca sp.
      organisms were noted in urine sediment and renal biopsy specimens. In the 2nd
      dog, acute renal failure was diagnosed after treatment for bacterial cystitis.
      After diagnosis of protothecosis, organisms were successfully isolated by aerobic
      urine culture. Both dogs with acute renal failure did not respond to conventional
      medical therapy. In total, Prototheca sp. was noted in urine sediment in 4 of 8
      dogs and successfully cultured from urine in 5 of 7 dogs. Four of 5 dogs had
      organisms noted in the kidneys on histopathologic examination. In all dogs, the
      species identified was P zopfii. Sensitivity testing of 3 isolates revealed wide
      differences in in vitro drug resistance. Examination and culture of urine is
      recommended as a practical method for diagnosis of systemic infection with
      Prototheca sp.

PMID- 15715060
TI  - Serum hepatitis associated with commercial plasma transfusion in horses.
AB  - This report describes 4 fatal cases of serum hepatitis associated with the
      administration of commercial plasma in the horse. Serum hepatitis in the horse is
      characterized by acute hepatic central lobular necrosis, and it has been
      associated with the administration of biological products of equine origin. None
      of these horses had a recent history of equine biologic-origin vaccination;
      however, they had received 1.5-5 L of commercial plasma, and in I horse, an
      additional 8 L of fresh blood. Acute, severe colic unresponsive to medical
      therapy, lethargy, or sudden death developed in these 4 horses 41 to 60 days
      later. Two of the horses developed encephalopathy, confirmed in 1 horse by the
      presence of severe diffuse Alzheimer type II astrocytes in the brain. Although
      the prevalence of serum hepatitis associated with the administration of
      commercial plasma appears to be low in the horse, it should be considered an
      uncommon but potentially fatal risk factor.

PMID- 15715061
TI  - Streptococcus equi infections in horses: guidelines for treatment, control, and
      prevention of strangles.

PMID- 15715062
TI  - Canine and feline blood donor screening for infectious disease.
AB  - Thousands of blood transfusions are performed each year on dogs and cats, and the
      demand for blood products continues to grow. Risks associated with transfusions
      include the risk of disease transmission. Appropriate screening of blood donors
      for bloodborne infectious disease agents should be performed to lessen this risk.
      Geographic restrictions of disease, breed predilection, and documentation of
      actual disease transmission by transfusion all are factors that might need to be
      considered when making a decision on what screening program to use. In addition,
      factors involving general health care and management of blood donors should be
      employed to further ensure blood safety.

PMID- 15715063
TI  - More than you wanted to know about sound fields.

PMID- 15715064
TI  - Predicting pure-tone thresholds with dichotic multiple frequency auditory steady
      state responses.
AB  - The accuracy of dichotic multiple frequency auditory steady state in predicting
      pure-tone thresholds at 0.5, 1, 2, and 4.0 kHz compared to an ABR protocol (click
      and tone burst at 0.5 kHz) were explored in a group of 25 hearing-impaired
      subjects across the degree and configuration spectrum. Mean steady state
      thresholds were within 14, 18, 15, and 14 dB of the pure tones at 0.5, 1, 2, and
      4 kHz, compared to the tone-burst ABR at 0.5 kHz pure-tone difference of 24 dB,
      and a click-evoked pure-tone (2-4 kHz) difference of 9 dB. Recording time for the
      steady state protocol was 28 minutes (+/- 11) compared to 24 minutes (+/- 9) of
      the ABR protocol. Degree of loss had a significant effect on steady state;
      configuration of hearing loss had a limited effect. Mf ASSR predicted thresholds
      with relative accuracy although some configurations showed discrepancies for low
      frequency estimates.

PMID- 15715065
TI  - A tutorial on complex sound fields for audiometric testing.
AB  - A fundamental understanding of soundfield characteristics in enclosed spaces is
      required in order to appreciate and predict the behavior of complex sound fields
      (i.e., sound fields created with at least two uncorrelated sound sources on
      different axes) used in auditory tests for evaluating hearing aid performance,
      especially speech-in-noise tasks. This article is a tutorial starting with
      idealized definitions of acoustical spaces. Next is an exploration of the
      interactions between practical sound fields and the enclosures that contain them,
      based on a synthesis of ideas formed from a review of classical acoustical theory
      combined with direct observation. Finally, the discussion turns to the
      application of complex sound fields for speech-in-noise testing in typical
      audiometric test rooms and a practical realization of such a sound field with
      consideration given to the limitations imposed by factors covered in the
      foregoing discussions.

PMID- 15715066
TI  - Development of a test environment to evaluate performance of modern hearing aid
      features.
AB  - This article describes a new test environment and materials with the potential to
      measure performance differences among different hearing aid signal processing
      methods and features. Normative data suggest a linearly predictable increase in
      difficulty on a speech-in-noise task as the masker changes from random noise to
      multiple-talker speech, and the number of talkers increases. Data collected with
      normal listeners revealed no differences across four test sites for the single
      loudspeaker (Noise-Front) results and some differences across test sites for the
      multiple loudspeaker results. Room dimension differences among audiometric test
      enclosures and diffusion (or lack thereof) of the maskers in the vertical and
      horizontal dimensions of the sound fields appear to account for performance
      differences for the multiloudspeaker arrays, confirming the need to limit maskers
      to aperiodic signals in rooms with controlled ceiling height or to establish
      norms for each test environment such that results obtained in different
      enclosures can be compared.

PMID- 15715067
TI  - Discrimination of speech sound contrasts determined with behavioral tests and
      event-related potentials in cochlear implant recipients.
AB  - Cortical potentials evoked with speech stimuli were investigated in ten
      experienced cochlear implant (CI, type Nucleus 24M) users using three different
      speech-coding strategies and two different speech contrasts, one vowel (/i/-/a/)
      and one consonant (/ba/-/da/) contrast. On average, results showed that, compared
      to subjects with normal hearing, P300 amplitudes were smaller; however, most
      latencies were within the normal range. Next, individual P300 measures in
      response to the two speech contrasts were compared to behavioral discrimination
      scores. Significant within-subject differences in P300 amplitudes and latencies
      were found for the three speech coding strategies. These differences were in
      agreement with the behavioral, strategy-dependent discrimination of the speech
      contrasts.

PMID- 15715068
TI  - A comparison of two approaches to assessment of speech recognition ability in
      single cases.
AB  - Single-case design with the randomization test (RT) has been proposed as an
      alternative to the binomial distribution (BD) tables of Thornton and Raffin
      (1978) to assess changes in speech recognition performance in individual
      subjects. The present study investigated whether data analyzed using both
      approaches would result in similar outcomes. Sixty-two adults with normal hearing
      were evaluated using phoneme scoring and a restricted alternating treatments
      design under two signal-to-noise conditions. Results revealed a significant
      correlation between the RT and a BD analysis using at least 50-word lists,
      although the BD analysis was a more sensitive measure. The absence of correlation
      between the RT with a BD analysis using 25-word lists challenges the common
      clinical practice of using reduced list size, and supports the use of phoneme
      scoring and other attempts to find clinically acceptable yet evidence-based
      solutions to overcome the conflict between time and accuracy.

PMID- 15715069
TI  - Federal demonstation project tackles diabetes with telemedicine.

PMID- 15715071
TI  - Making the grade: online training as a cost effective and clinically efficient
      alternative in staff education.

PMID- 15715070
TI  - Towards creating an informatics infrastructure in home health care.
AB  - Although information technology is utilized successfully in many industries, its
      use in health care-and home health care in particular--continues to lag. This
      column summarizes a recent article by Bakken and Hripcsak (2004) examining the
      potential for informatics to improve patient care quality in home health care by
      supporting evidence-based practices and patient safety. The authors provide
      definitions of the basic components of an informatics infrastructure e.g., data
      mining, digital sources of evidence, etc.--and recommend how to make an
      informatics infrastructure for the home health care industry a reality.
      Suggestions include: (1) integrating informatics into education and training; (2)
      creating public/private partnerships among government agencies, vendors, and
      industry associations; and (3) performing cost-effective analyses to determine
      the optimal uses of specific technologies.

PMID- 15715072
TI  - Rep. Elijah Cummings seeks to fill information vacuum on home care & hospice
      servicces.

PMID- 15715073
TI  - A place unlike any other.

PMID- 15715074
TI  - Q&A: Surveys & certification and the Medicare hospice benefit.
AB  - Each year at the National Association for Home Care & Hospice (NAHC) National
      Policy Conference, the Hospice Association of America (HAA) sponsors a workshop
      featuring a panel of hospice experts from t he Centers for Medicare & Medicaid
      Services (CMS). Panel members are available during this time to take and respond
      to questions regarding the Medicare Hospice Benefit (MHB). The following
      questions and answers are excerpted from last year's CMS Hospice Expert Panel
      Workshop.

PMID- 15715075
TI  - The Client-driven business.

PMID- 15715076
TI  - Technology at work in home care marketing strategies.
AB  - In today's very competitive home care marketplace, an agency must be able to
      effectively differentiate itself This capability may be the single most important
      thing an agency can do to market its services. How a business stacks up against
      its competition dictates the difference between rapid growth and stagnation.
      Fortunately, modem technology provides many opportunities to establish
      competitive and strategic advantages in today's market.

PMID- 15715077
TI  - Joinng the ranks: nurses as role models.
AB  - The average age of today's nurse is 45. The average age of today's nurse educator
      is 55. Not only is the mean age of nurses increasing, but the United States is
      also facing a national nursing shortage crisis--with fewer and fewer nurses both
      in the field and entering the profession. Massive advertising campaigns
      highlighting flexible nursing opportunities, increased incentives from health
      care agencies in need of nurses, and newly created flexible shift opportunities
      for nurses include strategies aimed at addressing this shortage. Fortunately,
      nursing education programs are seeing an increase in applicants, and many schools
      of nursing are filling their slots for new students to capacity. But this problem
      will not be solved by solely tempting new recruits.

PMID- 15715078
TI  - Live for today.

PMID- 15715079
TI  - Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1
      associated peripheral nerve sheath tumors: II. The role of dysregulated growth
      factor signaling.
AB  - Patients with neurofibromatosis type 1 (NF1), one of the most common genetic
      disease affecting the nervous system, develop multiple neurofibromas that can
      transform into aggressive sarcomas known as malignant peripheral nerve sheath
      tumors (MPNSTs). Studies of human tumors and newly developed transgenic mouse
      models indicate that Schwann cells are the primary neoplastic cell type in
      neurofibromas and MPNSTs and that development of these peripheral nerve sheath
      tumors involves mutations of multiple tumor suppressor genes. However, it is
      widely held that tumor suppressor mutations alone are not sufficient to induce
      peripheral nerve sheath tumor formation and that dysregulated growth factor
      signaling cooperates with these mutations to promote neurofibroma and MPNST
      tumorigenesis. In Part I of this review, we discussed findings demonstrating that
      a loss of NF1 tumor suppressor gene function in neoplastic Schwann cells is a key
      early step in neurofibroma formation and that progression from neurofibroma to
      MPNST is associated with abnormalities of additional tumor suppressor genes,
      including p53, INK4A, andp27(kip1). In Part II of this review, we consider
      evidence that dysregulated signaling by specific growth factors and growth factor
      receptors promotes the proliferation, migration, and survival of neoplastic
      Schwann cells in neurofibromas and MPNSTs.

PMID- 15715080
TI  - Molecular genetic analysis of oligodendroglial tumors.
AB  - Deletions on the short arm of chromosome 1 (1p) and the long arm of chromosome 19
      (19q) are molecular hallmark lesions of oligodendroglial tumors. Ever since
      oligodendroglial tumors with 1p and 19q deletions were shown to respond to
      chemotherapy, neuropathologists have been facing increasing requests for such
      molecular analysis. Therefore, there is increasing demand for reliable and simple
      assays. This brief report compiles information on different technical approaches,
      including manual and automated loss of heterozygosity analysis, fluorescence in
      situ hybridization techniques, and quantitative polymerase chain reaction. Herein
      we present a detailed protocol describing loss of heterozygosity analysis with
      microsatellite markers currently in use for two multicenter studies.

PMID- 15715081
TI  - Calpain inhibitor inhibits p35-p25-Cdk5 activation, decreases tau
      hyperphosphorylation, and improves neurological function after spinal cord
      hemisection in rats.
AB  - Aberrant calpain activation is a key mediator of neuron death. We examined the
      cell-permeable calpain inhibitor MDL28170 in the pathophysiological processes
      after spinal cord injury (SCI) including p35-p25- cyclin-dependent kinase-5
      (Cdk5) activation, tau hyperphosphorylation, neuron cell death, calpain I
      activation, astrogliosis, and microglia activation. Our study showed that
      intrathecal administration of MDL28170 improved neurologic dysfunction, prevented
      neuron loss, decreased the number of apoptotic cells, and abated astrogliosis and
      microglia activation 7 days after spinal cord hemisection in rats. Reverse
      transcription polymerase chain reaction demonstrated calpain inhibition
      significantly attenuated the ratio of proapoptotic Bax/anti-apoptotic Bcl-2 mRNA
      in the lesion and penumbra after SCI. Calpain, the calcium-activated proteolytic
      enzyme, was found to digest p35 to its truncated product, p25. Moreover, abnormal
      Cdk5 activation by p25 and subsequent tau hyperphosphorylation triggers
      pathologic events leading to neurodegeneration and neurofibrillary tangles. We
      found p35-p25-Cdk5 activation and tau hyperphosphorylation in SCI, and then we
      showed that intrathecal MDL28170 treatment could diminish p35 truncation, and
      abrogate aberrant tau phosphorylation. Double labeling of calpain I and
      phosphorylated tau (AT8) in the same cells of spinal cord lesion further
      implicated pathogenesis of SCI. In conclusion, MDL28170 abated calpain I
      activation, inhibited apoptosis and neuron loss, quenched microglia and astrocyte
      activation, and significantly improved neurologic deficit one week after spinal
      cord hemisection. The neuroprotective mechanisms of calpain inhibitor in SCI
      could be attenuating upregulation of Bax/Bcl-2 ratio, preventing p35 truncation
      in the lesion and penumbra, and abrogating tau hyperphosphorylation.

PMID- 15715082
TI  - An essential role for tumor necrosis factor in the formation of experimental
      murine Staphylococcus aureus-induced brain abscess and clearance.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of the immune
      response to pathogens, but may also exert neurotoxic effects, thereby
      contributing to immunopathology. To define the role of TNF during the course of
      brain abscess, TNF-deficient (TNF(0/0) mice were stereotaxically infected with
      Staphylococcus (S.) aureus-laden agarose beads. In comparison to 100% survival of
      wild type (WT) mice, TNF(0/0) mice displayed high mortality rates (54%) in the
      initial phase of abscess development as well as significantly increased morbidity
      in the course of the disease. The worse clinical outcome was due to an increased
      intracerebral (i.c.) bacterial load in TNF(0/0) mice as compared to WT mice. The
      impaired control of S. aureus was associated with reduced inductible nitric oxide
      synthase (iNOS) mRNA and protein expression in TNF(0/0)mice. Similarly, numbers
      of inflammatory leukocytes, cytokine expression of IL-6, IL-12p40, IFNgamma IL
      beta mRNA, and brain edema were significantly increased in TNF(0/0)mice as
      compared to WT animals. In addition, resolution of i.c. infiltrates was delayed
      in TNF(0/0)mice correlating with reduced apoptosis of inflammatory leukocytes and
      formation of a fibrous abscess capsule. Collectively, these data demonstrate that
      TNF is of key importance for the control of S. aureus-induced brain abscess and
      regulates the ensuing host immune response.

PMID- 15715083
TI  - Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal
      regeneration and functional recovery after complete transection of adult rat
      spinal cord.
AB  - The aim of this study was to evaluate whether transplantation of Schwann cells
      derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration
      and functional recovery in completely transected spinal cord in adult rats. Bone
      marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in
      vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level.
      An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and
      BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap.
      In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase
      immunoreactive nerve fibers was significantly higher compared to the MG group,
      although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive
      fibers were rarely detectable in both groups. In the BMSC-SC group, significant
      recovery of the hindlimb function was recognized, which was abolished by
      retransection of the graft 6 weeks after transplantation. These results
      demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of
      lesioned spinal cord, resulting in recovery of hindlimb function in rats.
      Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord
      injury.

PMID- 15715084
TI  - Genetically dominant spinal cord repair in a murine model of chronic progressive
      multiple sclerosis.
AB  - For reasons that are not well understood, central nervous system repair in
      multiple sclerosis is often minimal. We present evidence, in a murine model of
      chronic progressive multiple sclerosis, that genetic factors can substantially
      influence remyelination, axonal integrity, and neurologic function. Four inbred
      mouse strains, SJL, B10.D1-H2(q), FVB, and SWR, developed extensive inflammatory
      demyelination by 3 months after infection with Theiler's murine encephalomyelitis
      virus. Demyelination continued lifelong in SJL and B10.D1-H2(q) mice, accompanied
      by axonal injury, minimal remyelination, and progressive motor dysfunction. In
      contrast, FVB and SWR mice showed less axonal injury, progressive remyelination,
      and stabilization of motor function. Genetic dominance of the reparative traits
      was demonstrated by crossing remyelinating strains (FVB and SWR) with
      nonremyelinating strains (SJL and B10.D1-H2(q)). All F1 mice developed a
      phenotype identical to FVB and SWR, showing extensive remyelination, partial
      preservation of axons, and preserved motor function. Analyses of viral RNA and
      antigen, immune cell infiltration, and antiviral antibody titers did not predict
      the phenotypic differences between strains. These results highlight the
      significant extent to which hereditary factors can control disease course and
      demonstrate that the switch from a pathogenic to a reparative phenotype can occur
      even after prolonged inflammatory demyelination.

PMID- 15715085
TI  - Mutant huntingtin protein: a substrate for transglutaminase 1, 2, and 3.
AB  - The most prominent neuropathologic hallmarks of Huntington disease (HD) are
      cortical and striatal perinuclear cytoplasmic aggregates and intranuclear
      inclusions of mutant huntingtin. Our laboratory previously demonstrated that
      huntingtin protein colocalizes with transglutaminase 2 and its product, the
      epsilon-(gamma-glutamyl)lysine bond in intranuclear inclusions in HD frontal
      cortex. We also found that transglutaminase 2 cross-links N-terminal fragments of
      mutant huntingtin (htt-N63-148Q-myc) in cells in culture. We now report a
      significant increase in transglutaminase 2 mRNA in HD cortex (225% of controls)
      and striatum (399% of controls). Expression of the short transglutaminase 2 mRNA
      splice variant was not detectable in HD, although previous studies demonstrated
      upregulation in Alzheimer disease and progressive supranuclear palsy. Cells co
      transfected with GFP-tagged transglutaminase 1, 2, or 3 and htt-N63-148Q-myc
      exhibit increased cross-linked huntingtin in the insoluble fraction of cell
      lysates. Treatment of cells with cystamine, a chemical inhibitor of
      transglutaminase, decreased aggregated and cross-linked huntingtin and increased
      viability of cells that were transfected with transglutaminase 2 and htt-N63-148Q
      myc. These data suggest that transglutaminase 1, 2, and 3 could be involved in
      cross-linking of huntingtin into intranuclear inclusions in HD and that
      inhibiting transglutaminase should be explored as a potential treatment strategy
      for HD.

PMID- 15715086
TI  - P0(106-125) is a neuritogenic epitope of the peripheral myelin protein P0 and
      induces autoimmune neuritis in C57BL/6 mice.
AB  - The present study describes a new model of autoimmune neuritis in C57BL/6 mice
      induced by immunization with the novel neuritogenic epitope P0(106-125), derived
      from mouse peripheral myelin protein P0. Immunization with this peptide in
      combination with pertussis toxin induced high levels of peptide-specific CD4+ T
      cells in spleen and popliteal lymph nodes. Clinical symptoms of autoimmune
      neuritis started with a flaccid tail at day 10 postimmunization (p.i.),
      progressed to moderate paraparesis at day 15 p.i., declining thereafter with
      undetectable symptoms at day 40 p.i. Clinical disease activity paralleled
      decreased sciatic nerve motor conduction and histopathologic alterations of
      sciatic nerves. These included inflammatory infiltrates, mainly consisting of
      inducible nitric oxide synthase (iNOS)+ macrophages and CD4+ T cells. These data
      fit into the pathogenetic concept of murine autoimmune neuritis as a CD4+ TH1
      cell-mediated disease. Our new mouse model provides an attractive tool to
      identify critical factors that regulate the severity of autoimmune responses in
      the peripheral nervous system.

PMID- 15715087
TI  - Expression patterns of cell cycle components in sporadic and neurofibromatosis
      type 1-related malignant peripheral nerve sheath tumors.
AB  - The molecular biology underlying the development of highly malignant peripheral
      nerve sheath tumors (MPNSTs) remains mostly unknown. In the present study, the
      expression pattern of 10 selected cell cycle components is investigated in a
      series of 15 MPNSTs from patients with (n = 9) or without (n = 5)
      neurofibromatosis type 1 (NF1). Thirteen tumors did not express the cyclin
      dependent kinase inhibitor, p16(INK4A), an observation that was related to
      homozygote gene deletions in three tumors, heterozygote deletions in five, and
      gross gene rearrangements in five. The absence of protein expression in the
      tumors with one seemingly intact allele was not caused by promoter
      hypermethylation of p16(INK4A) or p14(ARF). All tumor samples expressed normal
      sized RB1, cyclin D3, CDK2, CDK4, p21(CIP1), and p27(KlP1) proteins, and only a
      single tumor showed an aberrant protein band for one of these proteins,
      p21(CIP1). Cyclin D1 was absent in four tumors; all except one tumor showed
      expression of TP53 protein, and three of nine MPNSTs had expression of normal
      sized MDM2. In conclusion, this study shows that the vast majority of MPNSTs had
      gross rearrangements of the p16(INK4A) gene, explaining the absence of the
      encoded protein in the same tumors. The level of expression was equally
      distributed between the familial (NF1) and sporadic cases, although it should be
      noted that the 2 cases with p16(INK4A) expression were sporadic. The data imply
      that the complete absence of p16(INK4A) is sufficient for activation of the cell
      cycle in most MPNSTs; thus, it is not necessary for tumor proliferation to
      further stimulate the cycle through alteration of other central components.

PMID- 15715088
TI  - Extracellular deposits of A beta produced in cultures of Alzheimer disease brain
      vascular smooth muscle cells.
AB  - Alzheimer disease (AD) and Down syndrome (DS) brains contain deposits of amyloid
      beta peptide that are located extracellularly in the neuropil and in blood
      vessels walls. A small fraction of brain Abeta is detected intracellularly in
      neurons, smooth muscle cells, and microglia. The roles of these extracellular and
      intracellular pools of Abeta in pathogenesis of AD-type dementia are
      controversial. Cell culture models of vascular amyloidosis-beta revealed
      intracellular, but not extracellular deposition of Abeta. Here we demonstrate for
      the first time, formation of extracellular deposits of Abeta in primary cultures
      of vascular smooth muscle cells isolated from AD cases with cerebrovascular
      amyloid angiopathy. Extracellular Abeta deposition required the use of cultures
      that produced high quantities of Abeta, which contained at least 50% of cells
      forming intracellular Abeta deposits, and providing extracellular matrix
      proteins. During 12 days of culture in this system, we observed accumulation of
      nonfibrillar, granular deposits in extracellular matrix, similar to early stages
      of vascular amyloidogenesis in vivo. This is a valuable system to study the
      effects of various potential amyloidogenic factors on formation of extracellular
      Abeta deposits.

PMID- 15715089
TI  - [Role of alpha-2 macroglobulin in oncologic diseases].

PMID- 15715090
TI  - [Frequency of polyneoplasia: coincidence of breast and thyroid cancer].

PMID- 15715091
TI  - [Adjuvant chemotherapy and chemoradiotherapy of operable gastric cancer: an
      overview].

PMID- 15715092
TI  - [Thyroid cancer in children and in the adult population in the Bryansk Region
      after the Chernobyl disaster].

PMID- 15715093
TI  - [Prospective study of families on a genetic cancer registry].
AB  - The Familial Cancer Register, Moscow, established in 1990, has a record of
      pedigrees of 6,000 cancer patients. The records on the probands and families have
      been studied since 1995. The paper presents the data of a repeat survey of the
      families conducted in 1990-1995. Only 794 out of 3,000 families, included in the
      first survey, responded. Relapse was reported in 135 probands and/or relatives
      from 108 families. The following subgroups were identified depending on the rates
      of cancer morbidity in familial histories (the criteria are presented): 1) no
      incidence; 2) few cases; (3) more cases, and (4) all family members have cancer.
      New tumors were detected in one-third of such families. A direct correlation was
      found between the morbidity rates and neoplasia incidence. In 12 families of
      group 3, originally, not all the members had tumors.

PMID- 15715095
TI  - [Principles of radiographic and endoscopic diagnosis of colorectal cancer].
AB  - An evaluation of the potential of X-ray and endoscopy diagnosis and preoperative
      staging of colorectal cancer has shown that the best results are to be obtained
      by their complex multistage and purposeful use. Timely examination heeding the
      specific features of either component will permit detection and identification of
      colorectal tumors according to International TNM classification.

PMID- 15715094
TI  - [Cognitive function in patients with endometrial and colorectal cancer:
      connection with hormonal and metabolic status].
AB  - Cognitive dysfunction may be associated with the presence of an array of hormono
      metabolic factors of risk for certain basic noninfectious diseases, supposedly,
      including cancer. The investigation was concerned with an appraisal of such
      cognitive functions as verbal and eye memory and ability to concentrate in
      endometrial and colorectal cancer patients versus hormonometabolic status and
      relevant parameters in menopausal women. The indices of short-term memory and
      concentration in endometrial carcinoma were significantly higher than both in
      colorectal cancer and osteoporotic patients. However, they were not among healthy
      women of the same age. A whole range of relationships between said indices and
      glucose- and estradiol levels in blood serum of patients was studied. No link was
      established between blood-serum cholesterol, b-lipoproteide and insulin
      concentration in patients, on the one hand, and cognitive function, on the other.
      Further research is expected to disclose the ties of the latter with other
      hormono-metabolic factors as well as tumor-related stress.

PMID- 15715096
TI  - [Influence of growth rates of local recurrences and in-transit metastases on
      survival of patients with cutaneous melanoma].
AB  - The growth rates of local recurrences and in-transit metastases of skin melanoma
      were assessed in 271 patients. Median growth rate in the course of chemotherapy
      was 0.02 a day--1 which corresponded to a doubling time of 34.7 days. Median
      survival time for patients with local recurrences and in-transit metastases was
      22.6 months, 12-month survival--70.1%, 5-year--19.6% and 10-year--9.9%. Growth
      rate appeared to be the most significant prognostic factor; similarly important
      were tumor volume, relapse-free interval, tumor mitotic rate, site and number of
      recurrences. The following additional characteristics of tumor growth rate have
      been suggested: maximum growth rate and doubling time limit, to assess the rates
      of secondary tumor focus development.

PMID- 15715097
TI  - [Inhibition of 1,2-dimethylhydrazine-induced carcinogenesis in rat gut by the
      antidiabetic drug Diabenol].
AB  - Diabenol, a new Russian antidiabetic drug, was used to investigate its effect on
      1,2-dimethylhydrazine (DMH)-induced carcinogenesis in rat large gut. Five doses
      of 21 mg/kg DMH were injected at an interval of one week. Administration of 10
      mg/kg diabenol with drinking water had no effect on either body mass or feed and
      water consumption. Yet, it was followed by a significant decrease in tumor
      incidence (4.22 vs. 5.77 tumors per tumor-bearers), frequency of neoplasms in the
      ascending colon (40.0% vs. 89.5%) and in their number (0.60% vs. 1.63 tumors per
      rat in a group). In the other groups, those indices tended to be still lower.
      Another tendency characteristic of the experimental group was a significantly
      high percentage of exophytic tumors (76.3% as compared with 50% in control)
      consisting of well-differentiated cells (47.4% and 14.7%, respectively) and with
      predominantly shallow invasion into the gut wall. Our results suggest the ability
      of the drug to inhibit DMH-induced carcinogenesis in the rat large gut.

PMID- 15715098
TI  - [Experimental study of ortho-toluidine carcinogenicity].
AB  - Ortho-toluidine carcinogenicity has been tested in chronic experiments using
      mice, rats and dogs. Tumors were induced in 19% of mice (lung and kidney
      adenomas, leukemia), rats--40% (subcutaneous fat tumors, mammary fibroadenomas,
      leukemia, renal tumors and hepatic sarcoma). Bladder tumors developed in two dogs
      after 9 and 10 years of experiment. Both literature and experimental evidence
      point to o-toluidine as a hazard to humans.

PMID- 15715099
TI  - [Angioroentgenologic response of rat M-1 sarcoma to low-energy infrared laser
      irradiation at varying frequency].
AB  - After rats with sarcoma M-1 inoculated in the femur area were exposed to low
      energy (0.54 mT1) infra-red laser irradiation, 100Hz, for 10 min, the number of
      contrast-enhanced vessels of tumor fell sharply as compared with controls. That
      effect lasted for almost 24 hrs. At 1kHz, the total-sum of diameters of such
      vessels still increased 24 hrs after the exposure. When at 10kHz, that index
      decreased, and by day 3 vascular pattern and diameter came back to normal in all
      experiments.

PMID- 15715100
TI  - [Experimental use of low-energy infrared laser radiation to stimulate antitumor
      effect of cyclophosphane].
AB  - The potential of increased antitumor effect of cyclophosphane used in conjunction
      with low-energy infra-red laser radiation was studied in sarcoma-45--bearing
      rats. Exposure to certain modes stimulated non-specific antitumor resistance and
      enhanced antitumor influence of the drug by reducing its damaging effect. Also,
      it inhibited refractory leukopenia and marked intoxication induced by
      antistressor reactions.

PMID- 15715101
TI  - [Criteria for suppressive dosage of thyroxine administered in thyroid cancer].
AB  - The investigation was concerned with thyroxine therapy for suppression of
      thyrotrophin synthesis in 1,033 out of 1,544 (66.9%) patients treated for
      papillary thyroid cancer (hemithyroidectomy--429, thyroidectomy--1,115; 484 of
      the latter group received radioiodinetherapy postoperatively). Thyroxine 2-5.2
      mg/body mass unit was administered for 1-10 yrs (average--4. yrs). Effective
      daily dose depended on extent of surgery: higher dosage was required after
      thyroidectomy than hemithyroidectomy, and it was significantly higher after
      radioiodinetherapy. Bringing thyrotrophin synthesis levels down to normal was
      necessary in a study based on body mass and height characteristics. Also, an
      inverse relationship was established between suppressive dose and age. Male
      patients appeared to require more thyroxine per day than women. Suppressive
      dosage of thyroxine with regard to age, sex and treatment modality is suggested.

PMID- 15715102
TI  - [Pre- and intraoperative radiotherapy for locally advanced gastric cancer in
      conjunction with extended lymph node dissection: results of phase II clinical
      study].
AB  - The paper discusses our findings on a phase II clinical study of an original
      procedure for therapy of locally advanced gastric cancer including pre- and
      intraoperative radiotherapy (IORT) and extended lymph node dissection. Out of 24
      patients, none had intraoperative complications while postoperative ones
      developed in 16%; lethality rate was 4%. As far as immediate results are
      concerned, intensive pre- and intraoperative radiotherapy proved fully compatible
      with any surgical procedure including extended and extended-combined ones.
      Survival rates (Kaplan-Meier) were: 1 yr--90 +/- 6%; 2-, 3-year--74 +/- 9%.
      Indications of adjuvant radiotherapy and approaches to its effective use are
      discussed.

PMID- 15715104
TI  - [A densitometric assessment of skeletal mineral levels in prostate cancer
      patients treated with hormones].
AB  - An assessment of the densitometry data on 76 patients established a progressively
      falling level of minerals in the skeleton as a result of treatment with hormones
      for prostate cancer. The basal mineral levels had been identified by means of
      dual-energy X-ray absorptiometry. While said changes were immediately caused by
      maximum androgen deprivation, tumor influence and medication contributed too.

PMID- 15715103
TI  - [Role of endovascular radiologic component in the combined therapy of locally
      advanced cervical carcinoma].
AB  - Data are presented on the treatment of 308 patients with cervical carcinoma stage
      II-IV. Standard combined therapy was given to 143 patients in control. The study
      group (165) received radiotherapy in conjunction with roentgeno-endovascular
      occlusion of the internal ileal arteries and/or regional chemotherapy. Use of the
      latter modality was followed by a significant rise in remissions and higher
      survival rate (58%) as compared with 45.9% in control.

PMID- 15715105
TI  - [Experience with therapy of prostate cancer in the Primorye Territory].
AB  - The paper deals with a clinical evaluation of the results and side-effects of
      hormonotherapy of 108 patients with prostatic cancer, aged 46-96. Among the most
      frequent side-effects were: gynecomastia, sexual and neurologic dysfunction.
      Ziproterone acetate was followed by less frequent side-effects than generic
      flutamide. Monotherapy was tolerated better than maximum androgen deprivation. No
      significant correlation was found between survival, lethality and serologic
      progression duration, on the one hand, and variety of antiandrogen or androgen
      deprivation technique, on the other.

PMID- 15715107
TI  - [Granular cell breast cancer stimulating fibroadenoma formation].

PMID- 15715106
TI  - [Use of fludarabin in conjunction with other cytostatics in the treatment of non
      Hodgkin lymphoma resistant to standard chemotherapy].
AB  - The investigation involved 50 patients (fludarabin+cyclophosphamide+prednisolone
      (FCP)--30; fludarabin+mitoxanthrone+prednisolone (FMP)--17;
      fludarabin+cyclophosphamide--3). FMP proved the most effective (60%). Yet, FCP
      results were clinically significant (29%). The efficacy of all the procedures was
      determined by morphological pattern and was reported in low- and
      intermediategrade non-Hodgkin's disease alone. Insignificant differences in
      partial remission duration and stabilization were observed between FMP and FCP,
      e.g. FMP's effect lasted 1 month longer. No complete remissions were reported;
      tolerance was reasonable. Tentative findings point to the marked efficacy of
      fludarabin, particularly, in combination with mitoxanthrone, cyclophosphamide and
      prednisolone for relapse or refractory low- and intermediate-grade non-Hodgkin's
      disease.

PMID- 15715108
TI  - [Quality of life in prostate cancer: methods of evaluation and their
      application].

PMID- 15715109
TI  - [Topographic preparation for irradiation of the retroperitoneal lymph nodes and
      spleen in patients with Hodgkin's disease].

PMID- 15715110
TI  - [Role of Tantum Verde in prevention and treatment of oral cavity mucosal damages
      after cytostatic and radiotherapy in cancer patients].

PMID- 15715111
TI  - Care and management of diabetic nephropathy (moderate to advanced renal
      involvement).
AB  - This paper describes the possible risk factors in the development of renal
      disease in diabetes mellitus. The aim of this paper is to identify and evaluate
      the care and management of patients with moderate renal impairment and to make
      recommendations for optimal renal referral.

PMID- 15715112
TI  - Overview of current therapy in diabetes mellitus.
AB  - Diabetes mellitus can be found world wide and is a disease effecting carbohydrate
      metabolism. An increase in the number of diabetic patients from 189 billion today
      to 324 billion worldwide in 2025 is predicted. More than ninety percent suffer
      from type 2 diabetes. Similar numbers are mentioned for the pre-diabetic stage of
      impaired glucose tolerance (IGT) and metabolic syndrome. It is an important task
      for the future to use adequate diagnosis-finding methods and therapies to discern
      and treat the disturbance of carbohydrate metabolism as early as possible and
      perhaps slow down further progress in the case of IGT or metabolic syndrome. This
      should minimize the risk of cardiovascular or organic damage. In contrast to the
      treatment of type 1 diabetes with intensive insulin regimens, therapy for type 2
      diabetes has changed noticeably in the last years. All treatment forms have to
      account for the results of recent studies which show evidence that long- and
      short-dated elevation of blood glucose, mostly postprandial appearing peaks can
      lead to vascular damage with all consequences. The main goal should be to adapt
      treatment individually, estimating the stage of the disease, the risk of
      developing or progression of micro- or/and macrovascular complications, present
      risk factors, age and abilities. Non-pharmacologic and pharmacologic approaches
      are available.

PMID- 15715113
TI  - Blood pressure and cardiovascular complications in diabetic dialysis patients.
AB  - Diabetic nephropathy is one of the most frequent causes of renal failure.
      Diabetes increases the cardiovascular risk by 2-4 times that of the general
      population; hypertension increases this risk. Diabetes is a factor that shortens
      the survival of renal patients. Appropriate hospital care and attention can
      diminish complications in these patients and improve quality of life.

PMID- 15715114
TI  - Management of diabetic nephropathy: epidemiology, pathogenesis of nephropathy and
      factors influencing progression.
AB  - Diabetes mellitus is a major scourge of the modern world and the complications of
      this disease are important causes of morbidity and mortality. It is expected that
      the prevalence of this disease will increase several fold in all regions of the
      world over the coming decades. The prevalence of type 2 diabetes (initial
      resistance to endogenous insulin, usually found in obese adults) is about nine
      times greater than that of type 1 diabetes (absence of insulin, usually found in
      children and young adults) and thus the burden of this disease is mainly of
      patients with type 2 diabetes. The many complications of diabetes mellitus
      include cardiovascular disease, retinopathy, nephropathy, peripheral neuropathy
      and peripheral vascular disease. These complications appear in patients with
      either type of diabetes. This monograph will be devoted to the discussion of
      diabetic nephropathy (DN).

PMID- 15715115
TI  - Coping and living well with diabetes and nephropathy.
AB  - Coping and living with diabetes and nephropathy is not easy. The illness may
      affect quality of life and can influence the person physically, psychologically
      and socially. Once on dialysis unfortunately, quality of life is influenced even
      more. In addition, health professionals demand a great deal of self-discipline in
      the care and management of the person's illness. To support the person with these
      demands it is important to provide good education, treatment and care with the
      aid of the multi-disciplinary team-approach involving a
      nephrologist/diabetologist, nurse-educator, dietician, exercise specialist and a
      social worker/counsellor. With a treatment plan in each discipline and regular
      aftercare appointments it is hoped that the person will be able to master his
      illness.

PMID- 15715116
TI  - Choice of renal replacement therapy in patients with diabetic end stage renal
      disease.
AB  - Diabetic nephropathy is becoming the leading cause of end-stage renal disease
      (ESRD) worldwide. Although the prognosis of patients with diabetes and ESRD
      receiving Renal Replacement Therapy (RRT) has improved greatly, the presence of
      pre-existing cardiovascular disease means that the survival and medical
      rehabilitation of diabetics continue to be inferior to that of non-diabetics. RRT
      should be initiated earlier in patients with diabetes than in non-diabetics and
      the main choices of modalities are: 1) haemodialysis (HD), 2) Peritoneal dialysis
      (PD), 3) Kidney transplantation alone (KTA) or 4) simultaneous kidney and
      pancreas transplantation (SPKT). The most common modality of RRT utilised in the
      diabetic patient remains HD but this method is associated with many clinical
      problems, in particular the managment of vascular access and frequent
      intradialytic hypotension. There is accumulating evidence demonstrating that both
      survival and medical rehabilitation of patients with diabetes and ESRD is
      superior after renal transplantation with or without pancreas transplantation.

PMID- 15715117
TI  - When to start dialysis in diabetic patients?
AB  - Diabetic nephropathy and diabetes related nephropathies represents one of the
      most common causes of end-stage renal disease (ESRD), and diabetic patients with
      chronic renal failure represent the most important high risk cohort of uraemic
      patients requiring renal replacement therapy. Interventions to slow progression
      of kidney disease and measures to reduce the risk of cardiovascular disease are
      highly effective in early renal damage and should be the main task of
      nephrologists, but diabetic patients are more frequently referred late to the
      nephrologist. Factors involved in the rate of mortality of diabetic patients with
      ESRD are multiple, including nutritional status, co-morbidity, age, etc, but the
      duration and quality of pre-dialysis nephrological care constitute a key for
      improving outcomes of diabetic patients with ESRD.

PMID- 15715118
TI  - Vascular access for dialysis in diabetic patients.
AB  - There is consent that arteriovenous fistulae as introduced by Brescia et al. (1)
      are the preferred choice in the field of vascular access for maintenance
      haemodialysis therapy. Worldwide, a rapidly growing population of older patients
      suffering from diabetes mellitus, mainly type 2, is observed. The pre-existing
      damage to the arterial and/or venous vascular anatomy and the high cardiovascular
      comorbidity makes it more difficult to construct and to maintain a well
      functioning arteriovenous fistula (AVF). Problems arise from specific
      complications of AVF in diabetic patients. Alternative types of vascular access
      are needed in case arteriovenous access fails completely or cannot be created. It
      is concluded that old and new techniques in creating, maintaining and revising
      vascular accesses should be critically revisited for the benefit of the diabetic
      patient. A new, particularly demanding field in nephrology asks for urgent
      answers.

PMID- 15715119
TI  - Nutritional counselling for diabetic renal patients.
AB  - A diabetic patient who develops nephropathy has to cope with two different diets.
      Healthy food guidelines have to be followed and attention paid to the spread of
      carbohydrates throughout the day because of the diabetes. Renal failure means
      that attention also has to be paid to protein, sodium, potassium and fluid intake
      and the diet can be confusing to patients. When dialysis commences the management
      of, and attention to the diabetes is sometimes a little forgotten. This article
      identifies problems and how they may be dealt with.

PMID- 15715120
TI  - Foot care education in renal patients with diabetes.
AB  - Foot complications are said to be the primary cause of hospitalization for
      patients with diabetes, resulting in enormous personal and financial costs. It is
      reported that end-stage renal disease (ESRD) diabetic patients with peripheral
      vascular disease have a much higher incidence of foot complications and increased
      risk for amputation. However, despite the serious financial burden caused by
      diabetic foot ulcers and their complications, the importance of diabetic foot
      care is still not fully recognised or supported. There is increasing evidence to
      suggest that education on foot care is essential for patients with diabetes.
      Studies have shown that simple techniques such as identifying those at risk of
      developing foot ulcers, educating patients about foot care that is tailored to
      meet the requirements of individual patient needs, educational background and
      learning ability can be of obvious benefit to people with diabetes and is cost
      effective.

PMID- 15715121
TI  - Transplant strategies for diabetic renal patients.
AB  - The strict control of glycaemia in the diabetic patient prevents severe long-term
      complications of diabetes. The most effective physiological method to control
      glycaemia in the type 1 diabetes patient is pancreas or pancreatic islet
      transplant. However, these types of transplants require chronic immunosuppressant
      treatment that leads to short and long term complications and are reserved for
      type 1 diabetic patients with life threatening complications (frequent
      unexplained ketoacidosis or hypoglycaemias). With regards to type 1 diabetics
      with end-stage nephropathy, simultaneous pancreas-kidney transplant has excellent
      results and makes it possible for the patient to be insulin and dialysis free. If
      vascular complications, especially coronary disease, make it impossible to
      perform a simultaneous pancreas-kidney transplant, kidney transplant alone will
      be indicated and, in the future, the patient may have access to the transplant of
      pancreatic islets when the technique is perfected. Type 1 diabetic patients who
      receive a living or cadaver kidney transplant, and later a pancreatic transplant
      show excellent results. Type 2 diabetics, in whom pancreas transplant is not
      indicated, as they do not have a total deficit of insulin, can have access to a
      kidney transplant if they reach end-stage nephropathy in spite of their more
      advanced age, as long as their vascular disease allows it. Transplant of cadaver
      islets is beginning to provide good results, thanks to new immunosuppressant
      protocols. This procedure does not require surgery, the islets being implanted
      into the liver by infusion through the vena porta. Obtaining islets from
      embryonic or adult tissue stem cells, although in an experimental phase, could be
      a reality in the near future.

PMID- 15715122
TI  - Diabetic nephropathy--who cares?
AB  - Diabetic nephropathy has become the most common single cause of Established Renal
      Failure (ERF) in the United States of America (USA) and Europe. In the United
      Kingdom (UK) diabetic nephropathy is seen in 18% of new patients requiring
      dialysis. In the USA 7.3% of all adults and 17.8% of those over 65 years have
      diabetes mellitus. Furthermore diabetic nephropathy is the cause of ERF in up to
      45% of patients on dialysis. Recently compiled data by the World Health
      Organisation (WHO) shows that approximately 150 million people worldwide have
      diabetes and predict that this number may well have doubled to 300 million by
      2025. These figures are clearly daunting and renal units must prepare themselves
      for the rising number of patients with diabetes needing renal replacement therapy
      (RRT) in the future. Renal specialist nurses do not always have a major role to
      play in the prevention of diabetic nephropathy. Their remit must be to try and
      delay the progression to ERF and perhaps more importantly to concentrate their
      efforts on their ERF patient population with diabetes that have co-existing
      diabetes related pathologies. This article will attempt to discuss how renal
      nurses can best expand/extend their skills and knowledge to provide effective
      care for this patient group, and explore whether developing new and innovative
      roles or just new ways of working is the way forward.

PMID- 15715123
TI  - Patient and professional partnership in diabetic nephropathy.
AB  - Diabetes mellitus (DM) is a complex multifaceted metabolic disorder characterised
      by chronic disease processes of hyperglycaemia and changes in the metabolism of
      carbohydrates, fats and proteins. It holds no boundaries with age, gender,
      culture or social strata. It is a life long disease process, which belongs to the
      individual, impacting on physical, social, psychosocial and spiritual life
      experiences. Diabetes is a worldwide burden to healthcare providers. In the
      United Kingdom (UK) 1.4 million people are affected with a suspected million
      people undiagnosed. A significant subgroup of patients with DM are predisposed to
      developing diabetic nephropathy, and it is now the single commonest cause of end
      stage renal failure, accounting for 16% of new patients taken on to renal
      replacement therapy each year. It is in this subgroup that other diabetes related
      complications such as retinopathy, neuropathy and peripheral vascular disease are
      also concentrated. Microalbuminuria is an early indicator of renal disease in
      diabetes, and also predictive of total mortality, cardiovascular mortality and
      cardiovascular morbidity. These associated macro and microvascular complications
      can result in high personal, social and financial costs of managing complications
      associated with diabetic nephropathy and end-stage renal disease (ESRD). Some
      ethnic groups are particularly vulnerable--in the UK, the incidence of ESRD in
      South Asians and African Caribbean's is three times higher than in White
      Caucasians, in part due to the high prevalence of diabetic nephropathy.

PMID- 15715124
TI  - The developing role of the renal diabetes nurse.
AB  - Diabetes as a chronic disease is often complicated in its management,
      particularly when combined with chronic and end-stage renal failure. Patients,
      carers and health care professionals are unfortunately often confused by either
      too little or conflicting advice provided by the two specialist teams. Within
      this context, the Renal Diabetes Nurse (RDN) role serves to bridge the gap by
      ensuring effective links and communication. Currently, renal referrals are made
      from surrounding secondary care settings and primary care GP practices. The
      expansion of renal outreach clinics, the appointment of new consultant
      nephrologists and the emergence of nurse-led clinics, reflects our continuous
      growth to meet the demand for renal services. The number of patients with renal
      failure and diabetes is set to increase as the acceptance criteria are clarified
      and referral routes made explicit. An ageing population with 21-62% of the renal
      population over the age of 65 (depending on the location of the renal unit),
      coupled with an increase in the Asian and African-Caribbean population all
      contribute to increased patient numbers. It is now well recognised that these
      patients often experience associated generalised atheroma and vascular
      calcification from inadequately managed hypertension and diabetes over a number
      of years. Consequently, this group of patients are often "high maintenance"
      requiring input from the multidisciplinary team on a continuing basis.

PMID- 15715125
TI  - Integration of herbal medicine in national health care of developing countries.

PMID- 15715126
TI  - Assessment of effectiveness of traditional herbal medicine in managing HIV/AIDS
      patients in South Africa.
AB  - BACKGROUND: Very few clinical studies have been conducted in South Africa to
      assess the value and efficacy of traditional herbal medicines that are commonly
      used by traditional healers for the treatment of HIV-positive patients.
      OBJECTIVE: To assess efficacy of a South African traditional herbal medicine in
      reducing viral load and increasing CD4+T cell counts of HIV/AIDS patients.
      DESIGN: A descriptive, prospective, follow-up study of 33 HIV-positive volunteers
      over a one year period. Viral load and CD4 counts were taken three times from
      each participant. SETTING: From November 2001 to October 2002, patients were
      treated at the Rustenburg Community Based Centre for traditional therapy.
      Clinical and paraclinical treatments and screening of patients were done at
      Pretoria Gynaecological Hospital. PARTICIPANTS: Seven men and 26 women aged
      between 22 and 43 years took part in a 12-month long follow-up study. HIV
      monitoring was done at the beginning and after 4 and 8 months in symptomatic and
      asymptomatic patients with CD4 counts below 200 cells/mm3 or viral load counts
      above 10,000 copies. INTERVENTION AND ASSESSMENT: ab mitio and after 4-months,
      viral load, CD4+T cell count, FBC, LFT, glycaemia, U/E, cholesterol, pap smear,
      clinical and subjective assessment, modern drugs plus hospitalisation for
      opportunistic infections and resuscitation where needed, powder or suspension of
      herbal medicine followed by meals. MAIN OUTCOME MEASURES: Improvement in overall
      health condition and immune system, increase in CD4+T cell count and decrease in
      viral load count. The two sample paired t-test was used to compare initial and
      final counts at the 5% level of significance and power of 80%. Ninety five per
      cent confidence intervals were obtained for differences between mean values.
      RESULTS: After four and/or eight months of therapy, significant health
      improvement was achieved: better physical appearance (80% of patients), increased
      appetite (65%), feeling of well-being (60%), disappearance of skin marks (70%)
      and urogenital lesions (100%), resumption of workplace duties (60%), weight gain
      (80%), significant reduction in viral loads (85.4%, p = 0.0015) and significant
      increase in CD4+ T cell counts (226%, p = 0.0000). CONCLUSION: Achievement of
      health improvement within eight months indicates that herbal medicine can be used
      as supplementary or alternative treatment for HIV/AIDS patients, and that it is
      an obvious immune system booster and probable "virus-cidal" factor. The apparent
      safety and efficacy of herbal medication warrants further research with a larger
      sample size of study.

PMID- 15715127
TI  - Anaemia in human African trypanosomiasis caused by Trypanosoma brucei
      rhodesiense.
AB  - OBJECTIVE: To find out if indeed anaemia is a major sign in human trypanosomiasis
      caused by Trypanosoma brucei rhodensiense. DESIGN: A one year cross-sectional
      study of all admitted and surveyed Trypanosoma brucei rhodensiense infected
      patients (June 2001-June 2002) SETTING: Nkhotakota District Hospital-Central
      Region of Malawi. RESULTS: After survey and investigations, 28 patients (16 males
      and 12 females) were admitted to Nkhotakota District Hospital with a parasite
      positive Trypanosoma brucei rhodensiense infection. Twenty four (85.7%) of them
      were anaemic. Their mean haemoglobin was 8.96 +/- 3.07 g/dl compared to controls
      that had a mean haemoglobin concentration of 12.17 +/- 1.35 g/dl (p < 0.000001,
      95% CI -4.342 to -2.0785) (n = 45). None of the trypanosomiasis infected
      individuals had schistosomiasis or hookworms. Two patients had malaria. One of
      them was an 18-year-old pregnant woman with hepatosplenomegaly, who developed
      ante partum haemorrhage. She was jaundiced and had haemoglobin of 10 g/dl. She
      died after two weeks following the diagnosis and treatment. The other was a two
      year-old girl who had haemoglobin of 8.4 g/dl. She also had hepatosplenomegaly.
      All the other patients looked well nourished with no other signs of chronic
      diseases. Hepatosplenomegaly was significantly related to the severity of illness
      (p = 0.011) but not to anaemia. CONCLUSION: Though basic, this study has shown
      that anaemia is indeed a complication of human Africa trypanosomiasis caused by
      Trypanosoma brucei rhodesiense. There is need for further investigation to
      investigate the type of anaemia that is caused by this disease.

PMID- 15715128
TI  - Features of isolated sleep paralysis among Nigerians.
AB  - BACKGROUND: There is paucity of studies on isolated sleep paralysis (ISP).
      OBJECTIVES: To explore the relationship of variables for ISP sufferers, and
      clarify factors predictive of ISP health behaviour (IHB--doing something to
      prevent further attacks). DESIGN: Cross-sectional study. SETTING: General
      population. MEASUREMENT: 24-item ISP questionnaire completed by respondents.
      SUBJECTS: One hundred and ten (38.2%m, aged 30.9 years). RESULTS: Mean ISP
      frequency in the lifetime, past year and past month, were respectively, 6.7,
      2.02, and 0.5; average duration of episodes was four minutes, and 63.6%
      experienced it while awakening from sleep. Using ICSD criteria, 2.7% had severe
      experience (i.e. at least once per week), 18.2% moderately severe (once per
      month) and 75.5% mildly severe (less than once per month), with no significant
      demographic associations. 56.4% were afraid of the experience, 76.4% had
      little/no worries that something was seriously wrong with their bodies; 39.1%
      cited supernatural causes, 35.5% cited physiological/psychosocial causes; and
      44.5% described a hallucinatory experience. 1.8% took medical measures, and 7.3%
      consulted a faith healer; 44.5% resorted to prayers and 41.8% did nothing to
      prevent further attacks. The primary determinant of IHB was being afraid of ISP.
      CONCLUSION: These findings have public mental health education, treatment and
      research implications.

PMID- 15715129
TI  - Index of potential contamination: Schistosoma haematobium infections in school
      children in the Ashanti Region of Ghana.
AB  - BACKGROUND: Children are acknowledged as the most vulnerable group to urinary
      schistosomiasis. OBJECTIVE: To determine the age group(s) of school children
      considered as the major contributor(s) to the spread of the disease. DESIGN:
      Observational/Prospective (concurrent) studies. SETTING: Barekuma, Aninkroma and
      Hiawo Besease, riparian communities in the Ashanti Region of Ghana. SUBJECTS:
      Hundred children each were randomly selected from Barekuma and Hiawo Besease
      basic schools with population age profiles between 4 and 18 years. They were then
      categorised into 4-6, 7-9, 10-12, 13-15 and 16-18 years, respectively. However,
      at Aninkroma, the entire school population of 119 pupils, aged between 4 and 15
      years were used. They were similarly grouped into 4-6, 7-9, 10-12 and 13-15
      years, respectively. Urine filtration method was used for isolation and
      enumeration of S. haematobium eggs from the subjects. The subjects were monitored
      through repetition of the experiment at fortnightly intervals over four weeks.
      MAIN OUTCOME MEASURES: Corrected relative Index of Potential Contamination (IPC)
      expressed as percentage after calculating the crude IPC. RESULTS: The age groups
      with the highest relative IPCs at Barekuma, Aninkroma and Hiawo Besease were 7-9,
      10-12 and 13-15 years, registering 35.6%, 53.9% and 57.7%, respectively. The age
      group 4-6 years consistently had the lowest IPC in all the communities.
      CONCLUSION: The age groups 7-9,10-12 and 13-15 years were considered to be the
      major transmitters of the disease in the communities.

PMID- 15715130
TI  - Salt intake in first degree relations of hypertensive and normotensive Nigerians.
AB  - OBJECTIVE: To determine the salt taste threshold (STT) and salt threshold (STT)
      and salt intake(SI) in first degree relations of hypertensive and normotensive
      Nigerians. Hence to determine the relevance of STT in the genesis of hypertension
      in the Nigerian Africans. The relevance of salt to the development of systemic
      hypertension continues to attract researchers. DESIGN: A comparative study of STT
      and salt intake in the first degree offspring of hypertensive and normotensive
      Nigerians. SETTING: University of Benin Teaching Hospital in Benin City, Edo
      state of Nigeria. SUBJECTS: Fifty three normotensives youths (31 males and 22
      females) whose parents were undergoing treatment at the university of Benin
      Teaching Hospital and 42 age and sex matched normotensive youths (22 males and 16
      females) of normotensive parents from similar socio-economic background were
      recruited for the study. METHODS: Salt intake was determined with Corning
      clinical flame photometer using 24 hour urine sample produced by each
      participants. STT was determined by a double blind method which employed the
      forced stimulus drop technique. RESULTS: STT and UNa+ were significantly higher
      in OH than in ON (p < 0.001). There was strong positive correlation between STT
      and UNa+ (r = 0.77); diastolic blood pressure (DBP) (r = 0.61); systolic blood
      pressure (SBP) (rg = 0.54) and mean arterial pressure (MAP) (r = 0.69)
      respectively (P < 0.001). UNa+ also strongly correlated with DBP (r = 0.59); MAP
      r = 0.60, and SBP (r = 0.36) respectively P < 0.001). CONCLUSION: The study
      suggests that OH probably consume more sodium than the ON. This tendency to
      increased sodium (salt) consumption is most likely genetically determined. There
      is a suggestion that alteration in STT and change in blood pressure tend to occur
      simultaneously.

PMID- 15715131
TI  - Carrier status for Listeria monocytogenes and other Listeria species in free
      range farm and market healthy indigenous chickens and ducks.
AB  - BACKGROUND: Listeria organisms are documented to be zoonotic; one of the sources
      of infection is the domestic fowl where it could occur as in apparent infection.
      The carriage of Listeria monocytogenes and other Listeria in indigenous birds has
      not been documented in Kenya. OBJECTIVE: To establish whether healthy looking
      indigenous chickens and ducks could be carriers of Listeria monocytogenes and
      other Listeria species. DESIGN: Field survey of indigenous chickens and ducks in
      three districts of Kenya. SETTING: Embakasi and Dagoreti divisions in Nairobi
      district; Athi river division in Machakos district; and Ngong division in Kajiado
      district, in Kenya. SUBJECTS: One hundred and thirty six indigenous chickens and
      39 ducks reared under free range scavenging system in Nairobi, Machakos and
      Kajiado districts, in Kenya, were sampled. METHODS: In surveying the birds, the
      cloacal and pharyngeal swabs were taken from each bird separately using sterile
      cotton--tipped applicator swabs. The swabs in saline were transported in a
      coolbox to the laboratory for bacterial isolation and characterization.
      INTERVENTIONS: None (only compared farmed and the traded birds). MAIN OUTCOME
      MEASURES: Isolation of Listeria species and pathogenicity of Listeria isolates.
      RESULTS: Two Listeria monocytogenes and seven other Listeria species were
      recovered from the oropharyngeal swab samples of farm and market chickens but
      none from respective cloacal swabs. No Listeria was recovered from either
      oropharyngeal or cloacal swabs of farmed duck and slaughter chickens. Traded
      chickens yielded more Listeria isolates as compared to farmed chickens.
      CONCLUSION: This study shows that indigenous chickens in Kenya are carriers of
      Listeria monocytogenes and other Listeria species.

PMID- 15715132
TI  - Sensitivity of Listeria species, recovered from indigenous chickens to
      antibiotics and disinfectants.
AB  - BACKGROUND: Resistance of bacteria to antibiotics and disinfectants has been
      reported widely in the world. Listeria monocytogenes is no exception, although
      normally it tends to be variably sensitive to many antibiotics and disinfectants.
      OBJECTIVES: To assess the susceptibility of Listeria isolates recovered from
      indigenous chickens to commonly used antimicrobials. DESIGN: Nine Listeria
      isolates recovered from village chickens were tested for sensitivity to commonly
      used antibiotics and disinfectants and compared with Listeria monocytogenes type
      strains (L028 and DGH), Staphylococcus aureus NCTC 6571 and Escherichia coli ATCC
      25922. SUBJECTS: Nine Listeria isolates. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Susceptibility to eight antibiotics and seven disinfectants. RESULTS:
      The nine Listeria isolates were sensitive to gentamycin (100%), kanamycin
      (88.9%), tetracycline (77.8%), cotrimoxazole (66.7%), chloramphenicol (66.7%) and
      resistant to ampicillin, augmentin and cefuroxime. There was no difference
      between the antibiotic sensitivity to the various Listeria isolates and Listeria
      monocytogenes type strains (P > 0.05). The isolates were sensitive to
      disinfectants; A (100%), B (88.9%), D (77.8%), E (77.8%) but resistant to, CF,
      and G. There was significant difference between the resistance of Listeria
      isolates to the various disinfectants at the varied dilutions and the resistance
      at the recommended user--dilution (P < 0.00293). CONCLUSION: This study has shown
      that some of the Listeria isolates were resistant to most common antimicrobial
      agents except gentamycin and disinfectant A. Hence the need to consider this
      resistance pattern for effective treatment and control of listeriosis.

PMID- 15715133
TI  - Halothane induced hepatitis: case report.
AB  - Halothane as a cause of hepatitis is rare and may be overlooked when evaluating a
      patient with sudden onset jaundice. A 34-year-old lady, a nurse, presented to the
      liver clinic with sudden onset non-pruritic jaundice. Viral and collagen
      serological tests were all normal, malaria and sickling tests were negative, but
      transaminases were elevated. She reported inadvertent exposure to halothane in
      surgical theatre where she works. She improved on conservative management, then
      had a re-exposure to halothane after three weeks and developed a similar clinical
      picture, which improved on conservative management. In an area endemic of
      malaria, hepatitis and haemolysing conditions like sickle cell anaemia, the
      diagnosis of halothane hepatitis requires high index of suspicion. The mechanism
      of halothane-induced hepatic damage in this patient is very likely idiosyncratic.
      This is because of the modest dose at first exposure and more severe clinical
      picture at re-exposure.

PMID- 15715134
TI  - Non-pulmonary causes of acute respiratory distress in neonates: report of two
      cases.
AB  - Acute respiratory distress (ARD) in neonates is a dangerous condition that is
      usually brought on by pulmonary dysfunction. Congenital diaphragmatic hernia and
      oesophageal atresia with tracheo-oesophageal fistula are examples of non
      pulmonary causes of acute respiratory distress. Though rare, they are potentially
      fatal and successful management entails a multidisciplinary approach, which
      includes surgical intervention, use of critical care facilities such as the
      intensive care unit and paediatric supervision. We present two cases, each
      outlining one of the above named non-pulmonary causes of ARD, its management and
      outcome. Management of the congenital diaphragmatic hernia (CDH) was successful
      and the baby is still doing well. The baby with oesophageal atresia (OA) died
      during treatment, though the therapeutic procedures undertaken are presented here
      for academic purposes.

PMID- 15715135
TI  - The Laugier-Hunziker syndrome.
AB  - Laugier-Hunziker syndrome is a rare, acquired, benign hyperpigmentation of the
      lips, oral mucosa and nails. Although it is a benign disorder, other pigmentary
      disorders affecting the oral mucosa and nails must be considered in the different
      diagnosis. We presented a case of Laugier-Hunziker syndrome, showed clinical and
      histopathologic features of the disease.

PMID- 15715136
TI  - Cystosarcoma phyllodes: report of two cases.
AB  - Cystosarcoma phyllodes is a rare predominantly benign tumour usually affecting
      the female breast. In a retrospective review of giant breast masses seen over a
      period of 20 years, we encountered two cases of this tumour, one benign and the
      other malignant, the latter exhibiting the very unusual feature of axially lymph
      node metastases. We present these two cases and briefly review the literature.

PMID- 15715137
TI  - Anterior spinal artery syndrome complicating aortic dissecting aneurysm: case
      report.
AB  - Spinal Cord ischaemia is rare in the absence of trauma. We report a case of a 45
      year old known hypertensive for six years, who presented with features of
      anterior spinal artery syndrome (ASAS) complicating acute dissection of the
      descending aorta. He developed sudden onset non-traumatic paraparesis,
      sphincteric dysfunction and dissociated anaesthesia with a sensory level at T6.
      This was preceded by a two weeks' history of severe, sharp, lancinating, tearing
      left parasternal chest pain radiating to the back. He was managed conservatively
      on pentazocine lactate (fortwin), calcium- and beta-blockers, steroids, anti
      platelet and free-radical scavengers. On the 8th day of hospitalisation, he had a
      sudden abdominal distension, bled from the nose and mouth, went into hypovolaemic
      shock and died within a time frame of two minutes. He was presumed to have had a
      progression of the aortic dissection with subsequent rupture. Dissecting aortic
      aneurysm could run a benign asymptomatic or a lethal course and a high index of
      suspicion is necessary. The lack of exhaustive diagnostic investigative tools as
      well as surgical intervention in the management of this patient in a developing
      country was highlighted as was possible that the patient could have been
      mismanaged.

PMID- 15715138
TI  - Flooding and communicable diseases fact sheet.

PMID- 15715139
TI  - Avian influenza, Viet Nam--update.

PMID- 15715140
TI  - History of upper extremity replantation in the Czech Republic and worldwide.
AB  - Replantation surgery is a specialization in plastic surgery which, in comparison
      with other disciplines, has a relatively short history of only forty years.
      Replantation surgery developed due to experience with macrovascular anastomosis
      and to the evolution of the operative microscope, special micro-instruments and
      ultra delicate suturing material. Due to these advances, it is possible to
      implement anastomosis of blood vessels with a diameter smaller than 1-2 mm. Each
      of the three pillars of microvascular surgery has its own history. This work
      outlines their use and the contribution of each to the development of
      microsurgery. Finally, it compares the development of replantation surgery in the
      Czech Republic and worldwide within a specific time frame.

PMID- 15715141
TI  - Vascular anatomy of the radius and ulna diaphyses in their reconstructive
      surgery.
AB  - The vascular factor in the unsuccessful healing of the osteotomised forearm bone
      is widely discussed in literature at the so-called "level operations" aiming at
      correcting the "ulna minus" variant in Kienbock's disease. The purpose of our
      study was to trace the nourishing vessels of the forearm bones from their source
      from which a. nutritia radii (ANR) and a. nutritia ulnae (ANU) is separated and
      to locate the foramen nutritium (FN) of the radial and ulnar bones diaphysis. The
      forearms of 70 upper extremities were dissected and 204 macerated radial bones
      and 134 macerated ulnar bones were investigated scopically and metrically. The
      results demonstrated that there is less variability of sources from which ANR was
      separated as compared to the variability of the sources from which ANU was
      separated. Foramen nutritium radii (FNR) and foramen nutritium ulnae (FNU) were
      located mainly along facies anterior and its edges margo anterior and margo
      interosseus and only in a few cases they were observed along facies posterior.
      The metrical investigations showed that FNR were located mainly in the second
      fourth along the bone length, between 30 and 40% from the radial bone length in
      the distal direction. FNU were located mainly in the second fourth along the bone
      length, between 30 and 50% from the ulnar bone length in the distal direction.
      The results for vascular anatomy of the forearm bones give grounds to assume that
      osteotomy with a subsequent shortening of the radius is more feasible than
      osteotomy with ulnar lengthening. The distal half of the radius, between the
      third and fourth quarter in particular, is also recommended as most suitable for
      surgical intervention.

PMID- 15715142
TI  - Treatment of non-melanoma skin cancer in North Sardinia: is there a need for
      biopsy?
AB  - Non-melanoma skin cancer (NMSC) is the most common type of skin cancer. Important
      controversial issues are the need for incisional biopsies, surgical margin, and
      timing of follow-up. METHODS: A retrospective study was undertaken on 2544
      lesions. Accuracy of diagnosis and prevalence of incomplete excision were
      evaluated, comparing clinical and histological diagnosis using chi2 tests with
      Yates' correction. Kaplan-Meier recurrence graphs have been obtained. RESULTS:
      Lesions were correctly diagnosed in 94% of basal cell carcinomas (BCC) and in 69%
      of squamous cell carcinomas (SCC) (p < 0.001). Positive margins on pathological
      examination were 6.6% for BCC and 6.8% for SCC. A significant difference for
      incomplete excision has been found for BCC in the face (p < 0.001). Kaplan-Meier
      survival curves showed a different pattern for BCC and SCC. CONCLUSIONS: On the
      basis of our data, if clinical diagnosis is BCC, excision and reconstruction may
      be undertaken without an incisional biopsy. Alternatively, if clinical diagnosis
      is SCC, it is advisable to consider an incisional biopsy, before definitive
      surgical treatment.

PMID- 15715143
TI  - Reconstruction of maxilla alveolus for application of dental implant in patients
      with cleft defect.
AB  - The prospective study of dental implant application into the reconstructed
      maxilla alveolus of cleft patients was started in 2001. Its aims are to specify
      precisely the indications, conditions and techniques, as well as the factors
      justifying the assumption that the results will be successful. Indication was
      based on an examination by a multidisciplinary therapeutic team (plastic surgeon,
      dental surgeon, orthodontist, and prosthetist), with the proviso that the patient
      should have a positive approach. Successful orthodontic treatment of intergnathic
      relation and shape of the dental arches served as the basis. It was followed by a
      reconstruction of the defective alveolus using autologous cancellous bone grafts,
      harvested from an iliac crest. Dental implants were inserted 12-15 weeks after
      the transplantation and subsequently a prosthetic component was applied with a
      time delay of at least 2 months. After the orthodontic preparation,
      reconstruction of the alveolus has so far been performed in 38 patients. Their
      age was at least 14 years, i.e. the age when growth of the orofacial region was
      finalised or already complete. The crucial tasks at this stage are to form a
      stable, three-dimensional voluminous alveolar crest, and to cover the grafts with
      a sufficient amount of quality soft tissue. We needed an average amount of 3.7
      ccm of cancellous bone graft for the reconstruction. This amount can be harvested
      only from an enchondral bone. For soft tissue shell the mucoperiosteal shift of
      flap from cleft segment was used. In more serious cases contralateral or even
      bilateral shift was performed. The relief of tissue tension was performed by
      double cut-back. Using the approach described we attained a 84.2% success rate.
      Our results and experience derived within this project show that the success rate
      of this procedure depends on the continuous flow of the alveolar arch with a good
      intergnathic relation, with a length of defect between crowns of border teeth of
      at least 8 mm. The original osseous walls of the defect must definitely be of
      suitable height. On-lay augmentation does not work in these cases. A subsequent
      pitfall lies in resorption of transplanted bone, which may be reduced due to an
      early load by a dental implant. During the three months after the reconstruction
      a spongy osseous graft matures enough to ensure the primary stability of a
      fixture. We emphasise the necessity of close co-operation of the therapeutic team
      in such cases.

PMID- 15715144
TI  - The influence of age and exercise on the mobility of hand joints: 2:
      Interphalangeal joints of the three phalangeal fingers.
AB  - This report is a continuation of the study about mobility of the
      metacarpophalangeal (MP) joints of the three-phalangeal fingers. We measured
      flexion of proximal (PIP) and distal (DIP) interphalangeal joints in university
      students (52 males and 49 females), senior citizens (30 males and 30 females),
      and pianists (21 males and 31 females). Students were considered as a control
      group characterized by normal mobility of hand joints. In all three groups, the
      smallest flexion in the PIP joints is in the little finger, in the DIP joints in
      the index and ring fingers. In the control group the flexion in the PIP joints is
      greater in females compared to males, in the DIP joints it is greater on the left
      side compared to the right. With the exception of DIP joints in females, the
      situation is also similar in seniors. In pianists, however, the gender and
      lateral differences are less pronounced, due to exercise. Seniors of both genders
      show significant limitation of flexion in all PIP as well as DIP joints, as
      compared to students, while pianists have the same range of flexion compared to
      students, which also corresponds to the situation in MP joints. The previous
      study, however, showed that pianists have a greater ability to abduct and
      hyperextend fingers.

PMID- 15715145
TI  - Nipple reconstruction by local flaps: a long-term comparative study between star
      and skate techniques.
AB  - Nipple reconstruction often gives the highest satisfaction to the patient despite
      being just a minor procedure. During the last 50 years, many techniques have been
      described in order to improve the cosmetic appearance. Star and skate flaps are
      two of the most frequently reported procedures. The aim of this study was to
      compare the personal experience of two plastic surgery departments that have been
      using these two different methods. Thirty patients have been included in this
      study. Nipple projection and cosmetic appearance have been evaluated by both
      patients and surgeons. Follow-up ranged between 1 and 5 years. Results have been
      compared. Both techniques proved to be versatile and valid. The skate flap seemed
      to keep projection for a longer time, while the star technique gave a better
      cosmetic appearance.

PMID- 15715146
TI  - Silastic sheet integrated polymethylmetacrylate splint in addition to surgery for
      commissure contractures complicated with hypertrophic scar.
AB  - Numerous appliances or methods have been used to manage perioral deep burns and
      resultant contractures, however, until now, no particular technique is considered
      to be the "ideal technique". In this article, a new modified design of an
      extraoral appliance, composed of polymethylmetacrylate and silicon sheet is
      introduced. Two female and one male patient of a mean age of 33 were included in
      the study. They had a common history of facial thermal injury and hypertrophic
      scar formation. All three had a history of failed preceding operations to release
      commissure contractures. The appliance was placed within 14 days following the
      operation and stretched continuously for 6 months. During 14 months of follow-up
      period, no recurrence was encountered and a relatively symmetrical and
      satisfactory mouth opening was obtained. Owing to the effect of the silicon
      sheet, a more smooth, flattened scar surface and pliable commissure was achieved.
      No ulcerations, or tissue breakdown was observed. Extraoral appliances composed
      of polymethylmetacrylate silicon sheet were considered to be practical,
      convenient and efficient for the postsurgical treatment of the oral commissure
      contractures complicated with hypertrophic scar formation.

PMID- 15715147
TI  - [Proteinuria-induced mechanisms of tubulointerstitial remodeling and
      possibilities of nephroprotection in glomerulonephritis].
AB  - The authors describe various mechanisms (including cellular and molecular ones)
      that mediate the realization of interstitial inflammation under the influence of
      proteinuria components. The paper covers epithelial cell transdifferentiation
      processes, the role of angiotensin II, transforming growth factor beta, nuclear
      transcription factor NFkB, chemokines, endothelial factors etc. The effects of
      drugs routinely used in nephrology at present (angiotensin converting enzyme
      inhibitors, statines etc.) are presented in a new way according to the modern
      conception of the mechanisms of proteinuria-induced renal interstitial tissue
      remodeling in glomerulonephritis. The authors consider administration of
      antichemokine agents, which influences chemokine/chemokine receptor system, to be
      a prospective independent immunotherapeutic direction in treatment, aimed at
      prevention of glomerulonephritis progression.

PMID- 15715148
TI  - [Fontan right heart bypass as a corrective procedure for congenital heart disease
      with single-ventricle hemodynamics].
AB  - Treatment of patients with complex cyanotic congenital heart disease is one of
      the most difficult problems in heart surgery. In a number of cases, when normal
      introcardiac hemodynamics is impossible to reestablish, the operation of choice
      consists in hemodynamic correction, which implies excluding the right heart from
      pulmonary circulation by rerouting venous blood directly to the lungs. The
      analysis of the outcomes of the operation, performed in various modification,
      shows that the most optimal method to date is extracardial bypass of the right
      heart with a valveless tubular prosthesis. This method is associated with a
      relatively rare early and long-term complications. Improvement of outcomes can be
      achieved mainly via dividing the correction procedure into stages, including
      bidirectional cavapulmanal anastomosis, and via thorough selection and
      preoperative preparation of patients.

PMID- 15715149
TI  - [Genetic vaccines].
AB  - Vaccination with DNA-vaccines is a new approach in immunization that implies
      application of genetic constructions coding certain proteins of various pathogens
      instead of conventional ways of vaccination with inactivated or attenuated
      microorganisms. The main advantage of this approach consists in possibility to
      induce immune response in cases when the disease cannot be prevented by routinely
      used prophylactic vaccines. This advantage is attributed to the ability of DNA
      vaccines to focus immune response (cellular, humoral or both) upon one or several
      certain pathogenic antigens, which is impossible in principle when conventional
      vaccines are used and does not occur during an infectious process. The efficiency
      of DNA-vaccines is currently being tested in various pre-clinical and clinical
      trials. Genetic vaccination has induced protective or therapeutic immune response
      in a significant number of these trials. However, despite numerous positive
      results, clinical use of DNA-vaccines has not been recommended yet.

PMID- 15715150
TI  - [Genetic polymorphism of clinical Mycobacterium tuberculosis strains circulating
      in the territory of Novosibirsk Region].
AB  - Mycobacterium tuberculosis strains isolated from patients treated at TB
      dispensary branches in different districts of Novosibirsk were studied by genetic
      analysis. The below molecular methods were used: 1. PCR with random primers; 2. A
      method based on variable number of tandem repeats in loci; 3. IS6110 inverse PCR.
      Thirty-five samples of genome DNA of M. tuberculosis isolated were analyzed. Each
      of the 3 methods detected the main group of isolates, which comprised 61.8% of
      closely related strains revealed by method 1, 75.8%--by method 2, and 74.3%--by
      method 3. The remaining clusters were represented by 1 to 4 strains. The data
      obtained denote a relative homogeneity of M. tuberculosis strains circulating in
      Novosibirsk Region. No interplay was detected between the clustering of isolates
      and the presence or absence of mutation in genes conditioning the resistance to
      antibiotics.

PMID- 15715151
TI  - [The role of tumor necrosis factor-alfa in the interaction between the macro- and
      microorganism].
AB  - The authors present a review containing their own and literature data on the role
      of cytokine TNF-alfa in infectious process on the part of the macro- and
      microorganism, paying special attention to the latter. The paper contains data
      from literature concerning the mechanism of the interaction between cytokine and
      eukaryotic cells and experimental data on direct interaction between cytokine and
      bacterial cells in vitro and in vivo.

PMID- 15715152
TI  - [Actinic apparatus of phagocytes is a target for pathogenic bacteria].
AB  - The interaction between pathogenic microorganisms and eukaryotic cells is a
      topical area of research in microbiology and molecular medicine. This problem has
      been the subject of much study both in this country and abroad since early
      nineties; legionella, listeria, clostridium and other bacteria pathogenic to man
      have been used as model organisms. The results of the authors' research and
      literature data analysis underlie the hypothesis of the important role of
      bacterial enzymes, which modify components of eukaryotic cell actinic apparatus,
      in the virulence of infectious pathogens. Change in the activity of actinic
      cytoskeleton under the influence of microbe products has been demonstrated to be
      an effective mechanism, promoting bacterial proliferation in human organs and
      tissues. Here actinic apparatus components acts as a target for both
      "intracellular" and "extracellular" pathogens.

PMID- 15715153
TI  - [The apoptosis-supressing activity of clamydia].
AB  - The paper covers data from literature, concerning the influence of bacteria upon
      apoptosis program of host's cells. The mechanisms of apoptosis induction and
      suppression, developed by bacteria and directed towards the maintenance of
      conditions favorable to the infection, are quite varied. These mechanisms are
      realized via complex interaction between biologically active bacterial molecules
      and particular targets of signal paths which lead to apoptosis. In intracellular
      parasitism the apoptosis-suppressing activity of bacteria may be considered to be
      one of the mechanisms of pathogenic organism's persistence which provide
      favorable conditions for the development of chronic infections. Infection caused
      by C. pneumoniae in human fibroblasts has been experimentally demonstrated to
      protect the cells from spontaneous and induced apoptosis.

PMID- 15715154
TI  - [Presentation of HIV epitopes by HBcAg].
AB  - The hepatitis B core antigen (HBcAg) was used to present the HIV epitopes and
      mimics selected by phage display. The HIV epitopes were inserted into the el loop
      of HBcAg. The influence of insertions on the ability of chimeric HBcAg to
      assemble itself was studied. Special soft was made use of to detect the
      regularities between certain physical-and-chemical properties of amine-acid
      residua (belonging to an inserted alien peptide) and the presence or loss of the
      ability of HBcAg to assemble itself. Recommendations are provided of how to
      overcome difficulties related with the presentation of alien epitopes.

PMID- 15715155
TI  - [Different systems of delivery of HIV-1 DNA vaccine encoding the multiepitope CTL
      immunogene].
AB  - We used, within the case study, virus-like particles (VLP) and attenuated strains
      of salmonella for the delivery of HIV-1 DNA vaccine encoding the multiepitope CTL
      immunogene. The immunogenicity of the thus obtained vaccine constructions was
      comparatively analyzed. All constructions were shown to be able of inducing, in
      immunized animals, both the specific T-cell responses and the synthesis of virus
      specific antibodies. The lowest level of immune response was registered in
      animals immunized by "naked" plasmid DNA. The delivery by plasmid DNA involving
      VLP or the attenuated strain of salmonella enhances the efficiency of the DNA
      vaccine presentation to the immune system.

PMID- 15715156
TI  - [The contribution of system regulation of pathogenicity-determining genes
      expression to the virulence of facultative intracellular parasites].
AB  - Bacteria which belong to the group of facultative parasites are capable of
      intensive proliferation both outside the organism and inside eukaryotic cells,
      thus often causing severe human and animal illness. The necessity of quick
      adaptation to the alteration of conditions after intrusion into the macro
      organism gave rise to the development of complex genetic systems, regulating the
      activity of various gene groups. The review, written by the example of two
      pathogen bacteria, the gram-positive Listeria monocytogenes and the gram-negative
      Legionella pneumophila, illustrates up-to-date data that concern system
      regulation of genes, coding pathogenicity factors, as adaptive response of a
      bacterium to changes in outer conditions within the infectious process.

PMID- 15715157
TI  - [Mediators. Evolution of the concept].
AB  - The authors review the up-to-date situation in the issue of chemical mediators,
      acting in the nervous system. Mediators are key intercellular informational
      molecules found in the brain and peripheral nervous system. Most scientists
      interpret the term "mediator" rather widely, whereas others define it very
      strictly and clearly. That is why in neurophysiology the question of what a
      mediator is has not been answered fully yet. It is clear from the given
      scientific and historical review, that every new substance (after the first one,
      acetylcholine) that has had pretensions of being called a mediator, has altered
      the criteria of it. The authors present the contemporary classification of
      mediators, belonging to different classes of chemical compounds. Special
      attention is paid to chemical agents formed in the organism, which have only
      recently been referred to the class of mediators (gases and D-amino acids).

PMID- 15715158
TI  - [Genetic transformation of Nicotiana africana Merxm. with plasmids containing lox
      recombination].
AB  - An efficient genetic transformation method for african tobacco Nicotiana africana
      Merxm. has been established. African tobacco is a valuable source for cytoplasmic
      male sterility (CMS) and nuclear encoded resistance to potato virus Y (PVY). N.
      africana transgenic plants have been obtained using both Agrobacterium-mediated
      and direct transformation of leaf explants with gold particle bombardment using
      particle inflow gun. Plasmid vectors containing phosphinothricin resistance gene
      (bar gene) coding region without promoter and independent 35S promoter between
      lox sites (lox-bar-35S-lox) and nptII gene were used. Transgenic plants were
      selected according to growth capacity on the selective medium containing 50 mg/l
      kanamycin. PCR analyses of kanamycin-resistant plants confirmed the presence of
      nptII and bar genes in their genome. Agrobacterium-mediated transformation of
      root explants has proved to be the most efficient transformation method for N.
      africana.

PMID- 15715159
TI  - [Study of plant extract activity in the system of Escherichia coli unstable
      mutants].
AB  - Ability of cell biomass extracts of some medicinal plants to inhibit spontaneous
      segregation of new forms in E. coli MS2-induced unstable mutants system has been
      shown. The effect described is analyzed from the position of stabilizing activity
      of extracts concerning bacterial envelope membranes. The possible use of this
      bacterial system to study stabilizing effect as a separate stage of the known
      antimutagen protective action is discussed.

PMID- 15715160
TI  - [Time-effect relationship for unstable chromosome exchange levels in Chernobyl
      clean-up workers].
AB  - The post-irradiation changes of dicentric and centric ring levels were studied in
      Chernobyl liquidators using the data of 507 individual chromosomal surveys of
      persons sampled at different time after their activities at Chernobyl NPP
      accident zone. The time-effect relationship within 0-10.5 years after exposure
      was displayed as exponential decline of the mean chromosome exchange frequency
      with average decay half-time 2.2 y. During 10.5-13 years after exposure the
      increasing and stabilization of chromosome exchange yield on the level 2-3-times
      higher than control was observed. In the first few months after irradiation the
      dicentric and centric ring frequency in liquidators had the clear reverse
      correlation with the duration of person's duties at the Chernobyl zone. The
      parameters of unstable chromosome exchange elimination were independent on the
      initially induced aberration yield, that resulted in earlier reaching the
      subcontrol level in persons who had more protracted duration of duties at the
      Chernobyl accident zone.

PMID- 15715161
TI  - [Molecular-genetic characteristics of Mycobacterium tuberculosis strains isolated
      in southern region of Ukraine].
AB  - Results of molecular-genetic analysis of Mycobacterium tuberculosis strains
      isolated from patients of Odessa and Nikolaev regions of Ukraine are represented.
      Occurrence of individual types of mutations in genes associated with rifampicin
      and isoniazid resistance has been studied for the first time. Data concerning
      prevalence of Beijing strains in the South of Ukraine are obtained.

PMID- 15715162
TI  - [Nucleolar organizer region activity in lymphoid cells of human lymphatic nodes
      in the norm].
AB  - Comprehensive approach to study nucleolar organizer region activity rating in
      lymphoid cells of 87 human normal lymphatic nodes was proposed. Possibility of
      visualization of basic morphofunctional nucleolar types and different subtypes of
      nucleolonemal nucleoluses was demonstrated at light microscopy level basing on
      7387 prolymphocyte nucleus research of argentophile granule allocation features
      and dimensions. Distribution index of extranucleolar argentophile granules was
      estimated. The complex of parameters of lymphoid cell nucleolar set can be used
      as control for study of different lymphoproliferative processes.

PMID- 15715163
TI  - [Variability and dynamics of micronuclei rate in participants of transatlantic
      march of the VIIth Ukranian Antarctic expedition].
AB  - The estimation of individual variability and group dynamics of micronuclei rate
      in buccal cells of participants of transatlantic march of the VIIth Ukrainian
      Antarctic expedition (Sevastopol--UAS "Akademik Vernadsky"--Sevastopol) was
      carried out. The general average rate of micronuclei was 2.20 per thousand.
      Individual values of micronuclei frequencies varied in wide limits. The maximum
      value of CV was 92.4% and the minimal one was 48.4%. Individual averages of
      micronuclei rates varied from 1.70 to 2.78 per thousand. Dependence of individual
      and group dynamics of micronuclei rates on environmental factors (temperature,
      atmospheric pressure and storm activity) was tested. No significant correlation
      of these parameters was found.

PMID- 15715164
TI  - Genotoxic activity of newly synthesized derivatives of cyano-pyridone in murine
      cells in vivo and in vitro.
AB  - Possible genotoxic activity of two newly synthesized cyanopyridone compounds [4
      (N-methyl-phalimidyl-3)-3-cyano-4-methyl-pyridone-2 (MPhCMP) and 1-(4
      hydroxyphenyl)-3-cyano-4-methyl-pyridone-2 (HCMP)] with in vitro antitumor
      activity was studied both in in vitro and in vivo murine test systems. In L5178Y
      mouse lymphoma cells, HCMP did not induce micronuclei (MN) at the highest
      available (because of toxicity) concentration (100 microg/ml), while MPhCMP at
      dose of 50 microg/ml induced 2.6-fold, and at dose of 100 microg/ml 3.95-fold
      increase of number of the cells with MN. The concentration of 100 microg/ml is a
      threshold of toxicity of MPhCMP. In experiments on possible DNA damaging activity
      (the comet assay) of both substances using the same doses as in in vitro
      mutagenesis assay, we did not reveal any evidence of DNA damage. The acute
      toxicity of compounds was studied on male Swiss albino mice. LD50 values of
      MPhCMP and HCMP were 177.5 and 288 mg/kg, respectively. MPhCMP was more potent MN
      inductor than HCMP (2.5-fold at doses equivalent to 1/2 of LD50). Both substances
      possessing in vitro antitumor activity along with weak genotoxicity have a good
      chance for successful in vivo antitumor studies in rodents.

PMID- 15715165
TI  - [X chromosome inactivation pattern in elderly women over 70 years of age].
AB  - In the present study we have analyzed X chromosome inactivation patterns in 40
      women aged from 74 to 85 years (mean age 78 years). The control group was 36
      women (mean age 30 years). The most common AR-assay was used to determine X
      inactivation patterns (the study of methylation patterns of HpaII site in human
      androgen receptor gene (HUMARA) by quantative PCR). The age dependence of X
      inactivation was not observed. We have detected skewed X-inactivation in three
      women among 40 (7.5%) elderly women comparing to two women among 36 (5.5%) women
      from control group. The difference was not found to be statistically significant.
      We made a suggestion that higher incidence of skewed X-inactivation in elderly
      women revealed by previous studies could occur due to some experimental
      ambiguities as heterogeneity of the group studied; inclusion of women having
      relatives with genetic abnormalities associated with skewed X-inactivation
      patterns; the difference of X chromosome inactivation skewing determination. We
      conclude that present study does not show X chromosome inactivation to be age
      dependent.

PMID- 15715166
TI  - [Molecular-cytogenetic identification of partial trisomy of a short arm of
      chromosome 8].
AB  - We present de novo diagnosed case of partial trisomy of short arm of chromosome 8
      with psyhomotoric delay and microanomalies. Inverted duplication of short arm of
      chromosome 8 was identified using molecular-cytogenetic method. This case is
      compared with literature data on the same cases. The further intensive study of
      such cases is necessary to delineate this chromosomal syndrome

PMID- 15715167
TI  - [FISH detection of spontaneous level of chromosome aberrations in peripheral
      blood lymphocytes in persons of different ages].
AB  - FISH-WCP method with fluorescent probes to chromosomes 1, 2, 4 was used for
      cytogenetical examination of two groups of male (middle age 23 and 53.5 years)
      who deny their deliberate contact with known or supposed mutagens. The wide inter
      individual variability of the stable chromosome aberration frequencies in each
      group has been shown (0.006-0.014 and 0.006-0.025 per cell per genome-equivalent
      correspondingly). The trend of increasing of the mean-group level of one-way and
      two-way translocations during aging has been revealed (0.009 and 0.013 per cell
      per genome-equivalent, correspondingly).

PMID- 15715168
TI  - [Signal role of nitric oxide in plants].
AB  - Discovery of nitric oxide (NO*) as a key endogenous molecule, which regulates
      metabolism among very distantly related organisms, stimulated intensive research
      related to its multiple functions in plants. NO* exerts its cellular effects as
      toxic agent, metabolism regulator, second messenger during elicitation of
      different defense responses. It can induce various processes in plants, including
      programmed cell death, stomatal closure, seed germination and root development.
      Currently, elucidation of NO* signaling role in regulation of cellular responses
      is a "hot spot" of modern cell biology.

PMID- 15715169
TI  - [Statistical analysis of genome].
AB  - The chemical structure of DNA is characterized by sequences of four basic
      nitrogens occurring in one of two nucleic acid chains and in a complementary
      fashion in the other. Markov chain is the aspect of probability theory that
      analyzes discrete states in which transition is a fixed probability not affected
      by the history of the system. It is shown that DNA is represented in the form of
      regular Markov chain. Ergodicity property and law of large numbers follow from
      the statistical analysis of stationary transition probabilities.

PMID- 15715170
TI  - Description of a 111-kb pathogenicity island (PAI) encoding various virulence
      features in the enterohemorrhagic E. coli (EHEC) strain RW1374 (O103:H2) and
      detection of a similar PAI in other EHEC strains of serotype 0103:H2.
AB  - Human infections with enterohemorrhagic E. coli (EHEC) strains of serotype
      O103:H2 are of increasing importance in Germany. As bovines are the principal
      EHEC reservoir behind the occurrence of human infections, we analyzed a
      pathogenicity island (PAI I(RW1374)) of bovine O103:H2 strain RW1374 to identify
      putative virulence features. This PAI I(RW1374) harbors a functional 34-kb locus
      of enterocyte effacement (LEE) core region and has a total length of 111 kb.
      About 43 kb upstream of the LEE core a gene cassette consisting of efa1/lifA gene
      and flanking IS elements suggests another putative transposon within the
      PAI(IRW1374). In addition, the ent gene, encoding a Shigella ShET-2 enterotoxin
      homologue, is present about 57 kb upstream of the LEE core. This PAI is therefore
      a complex assembly of various virulence determinants including the efa1/lifA and
      the ent gene resembling O157:H7 PAI OI-122/SpLE3 as well as the LEE core region.
      An integrase gene on the very left end of PAI I(Rw1374) is disrupted by an IS629
      homologue. In an attempt to mobilize the LEE core we performed conjugation,
      transformation and transduction experiments. We were, however, unable to mobilize
      the whole or even single regions of PAI I(RW1374). Comparative studies with other
      strains of serotype O103:H2 isolated from humans, bovines and food showed that
      they all harbored a similar phe V-inserted PAI including the virulence genes ent
      and lifA/efa1 as well as the large virulence-associated plasmid encoding the EHEC
      hemolysin. This combination of several virulence factors confirms the complex
      virulence of O103:H2 EHEC and may at least partly explain the high virulence of
      this EHEC serotype in humans.

PMID- 15715171
TI  - Placental and intestinal alkaline phosphatases are receptors for Aeromonas sobria
      hemolysin.
AB  - The Aeromonas sobria hemolysin causes diarrhea following infection by this
      enteropathogenic bacterium. We previously identified the putative receptor for A.
      sobria hemolysin as a p66 protein on Intestine 407 cells (Microb. Pathog. 27
      (1999) 215-221). Here, we have partially purified and obtained a peptide mass
      fingerprint of p66 which revealed its identity with placental alkaline
      phosphatase (PLAP). Recombinant PLAP expressed in 293T cells was also found to
      bind to hemolysin and the binding was found not to be dependent on the N-linked
      glycosylation of PLAP. By immunohistochemical analysis, PLAP expression was
      detected in human intestinal mucosa, the target tissue in disease. In addition to
      PLAP, hemolysin also binds to intestinal alkaline phosphatase (IAP), an enzyme
      that is also abundantly expressed in intestine. Thus, both PLAP and IAP are very
      likely involved in the pathogenesis of diarrhea caused by this bacterial toxin.

PMID- 15715172
TI  - Immune response to vaccines based upon the VapA protein of the horse pathogen,
      Rhodococcus equi, in a murine model.
AB  - Rhodococcus equi is a significant pathogen in foals predominantly causing a
      pyogranulomatous bronchopneumonia. Many vaccine candidates have been tested for
      the prevention of R. equi disease in foals. However, none of these have been
      developed for widespread commercial use. Previous studies have shown that a Th1
      immune response is imperative for the protection of foals against R. equi
      disease. In this study a DNA and a protein vaccine based upon the well
      characterised R. equi virulence-associated protein VapA were developed. The
      vaccines were tested in the BALB/c murine model and the results showed that both
      vaccine candidates elicited a Th1-type response in the host. Upon
      coadministration of an IL-12 expression plasmid with the DNA vaccine, an increase
      in the Th1 response was observed. However, when mice were challenged with 1.5 x
      10(7) virulent R. equi ATCC 33701 none of the vaccinated mice showed protection
      apart from the mice immunised with live R. equi. These results indicate that
      despite their immunogenicity the VapA-based DNA and recombinant protein vaccines
      developed in this study were unable to prevent bacterial replication following a
      high-dose systemic challenge with virulent R. equi in the BALB/c model.

PMID- 15715173
TI  - First steps towards the genetic manipulation of Mycoplasma agalactiae and
      Mycoplasma bovis using the transposon Tn4001mod.
AB  - Mycoplasma agalactiae and M. bovis rank amongst the most serious pathogenic
      mycoplasmas infecting small ruminants and cattle, respectively. Despite
      considerable advances made in Mycoplasma molecular genetics in the past decade,
      there is still a complete lack of genetic tools to assess the pathogenic
      mechanisms of these two species. Studies were undertaken to develop a genetic
      system for the analysis of potential virulence factors of these pathogens.
      Transposon Tn4001mod was successfully introduced into various chromosomal sites
      of M. agalactiae and M. bovis with an optimal frequency of 10(-6) per viable
      colony-forming unit (CFU). This is the first report that demonstrates the
      amenability of these agents to transformation and to genetic manipulation.
      Furthermore, Tn4001 is implicated as the first potential genetic tool available
      for these ruminant pathogens.

PMID- 15715174
TI  - Characterization of Borrelia burgdorferi sensu lato isolated in Moscow province-
      a sympatric region for Ixodes ricinus and Ixodes persulcatus.
AB  - The relationships between Borrelia species and the vector ticks, Ixodes
      persulcatus and Ixodes ricinus were examined in a molecular epidemiological
      study. We conducted a survey in the Moscow region which is a sympatric region for
      both species of tick. We examined 630 unfed I. ricinus and I. persulcatus, ticks
      collected from four different regions around Moscow within an area of 250 km2.
      Eighty-four ticks were culture positive (13.3%) and the prevalence rate varied in
      each region from 5.7% to 42.3%. No difference was found between the total
      prevalence rate for both species. Eight Borrelia afzelii-like variant isolates
      from I. ricinus and Clethrionomys glareolus were identified as B. afzelii by
      flagellin gene and 16S rDNA sequence analyses. Most isolates from I. ricinus were
      identified as Borrelia garinii type 20047 and B. afzelii. Two isolates were
      identified as Borrelia burgdorferi sensu stricto (s.s.) and Borrelia valaisiana,
      respectively, but no B. garinii type NT29 was found. In contrast, isolates from
      I. persulcatus were identified as both types 20047 and NT29 of B. garinii, and B.
      afzelii. No B. burgdorferi s.s. isolate was found among isolates from I.
      persulcatus.

PMID- 15715175
TI  - Micromonas (Peptostreptococcus) micros: unusual case of prosthetic joint
      infection associated with dental procedures.
AB  - Micromonas (Peptostreptococcus) micros is frequently associated with periodontal
      disease as well as respiratory, gastrointestinal and female genitourinary tract
      infections, but only rarely has been reported as a pathogenic agent of prosthetic
      joint infections. Here we describe a case of a 63-year-old woman with prosthetic
      joint infection of total hip arthroplasty caused by the anaerobic species
      Micromonas micros, associated with tooth extraction. Samples obtained
      intraoperatively and from the oral cavity were positive for the presence of M.
      micros by culture and by real-time PCR. This case report indicates that
      infections of prosthetic joints can be associated with dental procedures and that
      sensitive molecular techniques are necessary for their routine diagnostic.

PMID- 15715176
TI  - Back to the future: using history as a lesson, not a location.

PMID- 15715177
TI  - Echocardiography "add-on" codes.
AB  - Doppler pulsed wave or continuous wave and color-flow velocity services are
      reported with add-on codes in addition to the basic echocardiography study. To be
      reimbursed, payor medical necessity guidelines must be met, and documentation in
      the echography report must clearly support all services performed.

PMID- 15715178
TI  - Implementing evidence-based practice for acute myocardial infarction utilizing
      automated information technology.
AB  - Saint Vincent Health Center has adopted 2 strong tools--evidence-based practice
      and automated information technology--to significantly improve mortality in
      patients with acute myocardial infarction. Automated information technology
      drives real-time evidence-based clinical processes and has reduced mortality from
      10% to 3% over a 1-year period.

PMID- 15715179
TI  - Rapid-cycle improvement in quality of care for patients hospitalized with acute
      myocardial infarction or heart failure: moving from a culture of missed
      opportunity to a system of accountability.
AB  - We describe a 1-year multidisciplinary initiative to improve the quality of care
      for patients with acute myocardial infarction and heart failure. In January 2002,
      this rapid-cycle improvement project began with a partnership of inpatient
      cardiology nursing and physician leadership. This inpatient leadership team
      analyzed clinical and operational processes, and revised and developed tools such
      as standard order sets, discharge instructions, clinical pocket guides, and daily
      monitoring logs. Once the tools and processes, were implemented, the team began
      "daily monitoring" to assess tool use. At the same time, a process was
      implemented to provide rapid feedback on key quality indicator compliance within
      a short time after discharge. At 12 months, quality improvements have been
      demonstrated.

PMID- 15715180
TI  - Efficacy of theophylline in people with stable chronic obstructive pulmonary
      disease: a systematic review and meta-analysis.
AB  - OBJECTIVES: To determine the efficacy of oral theophylline compared with placebo
      in people with stable chronic obstructive pulmonary disease (COPD). METHODS:
      Systematic review of randomized-controlled trials comparing oral theophylline
      with placebo for a minimum of 7 days in people with stable COPD. RESULTS: Twenty
      randomized-controlled trials were included in this review. The following outcomes
      showed significant improvement with theophylline compared with placebo: FEV1 and
      FVC both improved with theophylline (weighted mean difference [WMD] 0.10 L; 95%
      confidence interval [95% CI] 0.04-0.16 and WMD 0.21 L; 95% CI 0.10-0.32,
      respectively). VO2 max also improved with theophylline (WMD 195.27mL/ min; 95% CI
      112.71-277.83), as did PaO2 and PaCO2 (WMD 3.18 mmHg; 95% CI 1.23-5.13 and WMD 
      2.36mmHg; 95% CI -3.52 to -1.21, respectively). Patients preferred theophylline
      over placebo (relative risk 2.27; 95% CI 1.26-4.11). Theophylline increased the
      risk of nausea compared with placebo (RR 7.67; 95% CI 1.47-39.94). CONCLUSION:
      This review has shown that theophylline still has a role in the management of
      stable COPD, and is preferred by patients over placebo. However, the benefits of
      theophylline in stable COPD have to be weighed against the risk of adverse
      effects.

PMID- 15715181
TI  - Mucociliary clearance in COPD can be increased by both a D2/beta2 and a standard
      beta2 agonists.
AB  - In addition to breathlessness and cough, excessive mucus production is one of the
      main symptoms of chronic obstructive pulmonary disease (COPD). Excess mucus
      coupled with deteriorating mucociliary clearance is associated with a decline in
      lung function and an increased risk of death from pulmonary infection. The effect
      of Viozan (Sibenadet HCl, AR-C68397AA), a novel dual D2 dopamine receptor, beta2
      adrenoceptor agonist, on mucociliary clearance was investigated together with
      that of a beta2-adrenoceptor agonist, salbutamol. Using a double blind, parallel
      group study design, 15 patients with COPD, all habitual smokers, were randomised
      to receive nebulised sidenadet (3mg tid; n = 7) or salbutamol (5mg tid; n = 8)
      for 10 days. Lung mucociliary clearance rates were measured, by a standard
      radioaerosol technique, before and after the treatment period, as were 24-h
      sputum volumes. Both sibenadet and salbutamol therapies resulted in significant
      (P<0.02) enhancement of lung mucociliary clearance. The 24-h sputum volume was
      significantly reduced following sibenadet therapy (P<0.03) whereas salbutamol
      therapy had no effect. Our results, in addition to illustrating the effects of a
      standard beta2 agonist on mucociliary clearance, strongly suggest the potential
      dual benefit of dual-agonist compounds in lessening sputum production whilst
      simultaneously enhancing mucociliary clearance. For reasons unconnected with the
      present study, development work on this specific formulation is no Longer
      proceeding.

PMID- 15715182
TI  - Past, present and future--beta2-adrenoceptor agonists in asthma management.
AB  - The beta-adrenoceptor agonists (beta-agonists) have been used to relieve
      bronchoconstriction for at least 5000 years. beta-agonists are based on
      adrenaline and early forms, such as isoprenaline, Lacked bronchial selectivity
      and had unpleasant side effects. Modern beta-agonists are more selective for the
      beta2-adrenoceptors (beta2-receptors) located in bronchial smooth muscle and have
      less cardiotoxicity. Traditional beta2-adrenoceptor agonists (beta2-agonists),
      such as salbutamol, terbutaline and fenoterol, were characterised by a rapid
      onset but relatively short duration of action. While valuable as reliever
      medication, their short duration gave inadequate night-time relief and limited
      protection from exercise-induced bronchoconstriction. beta2-agonists with longer
      durations of action, formoterol and salmeterol, were subsequently discovered or
      developed. When combined with inhaled corticosteroids they improved lung
      function, and reduced symptoms and exacerbations more than an increased dose of
      corticosteroids. However, tolerance to the bronchprotective effects of long
      acting beta2-agonists and cross-tolerance to the bronchodilator effects of short
      acting beta2-agonists is apparent despite use of inhaled corticosteroids. The
      role of beta2-receptor polymorphisms in the development of tolerance has yet to
      be fully determined. Formoterol is unique in having both a long-lasting
      bronchodilator effect (> 12 h) and a fast onset of action (1-3min from
      inhalation), making it effective both as maintenance and reliever medication. The
      recent change in classification from short- and long-acting beta2-agonists to
      rapid-acting and/or long-acting agents reflects the ongoing evolution of beta2
      agonist therapy.

PMID- 15715183
TI  - Bullous emphysema versus diffuse emphysema: a functional and radiologic
      comparison.
AB  - The contribution of bullous emphysema (BE) to the functional impairment of
      patients with concomitant diffuse emphysema (DE) and the confounding effects of
      BE on functional measurements were investigated. Twenty-nine patients (Group I),
      with BE and DE were compared with a group of patients without BE matched, among
      other criteria, for radiographic extent of DE (Group II). Group I showed
      significantly lower PaO2, FEV1 and DLCO values and higher MRC score than Group
      II. In Group I the radiographic extent of BE and the extent of DE did not predict
      the functional impairment. The FEV1/FVC ratio in the subgroup with BE extent >
      25% of total lung volume was higher than in subgroups with BE extent > 20% and
      15%, respectively. In the same subgroups the correlation between DE and DLCO
      increased with the extent of BE. We conclude that BE contributes to the
      functional impairment of patients with concomitant DE. The confounding functional
      effect of bullae depends on BE extent: relatively milder obstruction can be
      observed with severe BE, whereas moderate BE causes modest deterioration of
      diffusing capacity, explaining the lack of functional-radiologic correlations in
      Group I. Therefore the computed tomographic scan is very useful in the work-up of
      BE with DE associated.

PMID- 15715184
TI  - Technical description of endoscopic ultrasonography with fine-needle aspiration
      for the staging of lung cancer.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) is a novel method for staging of the
      mediastinum in lung cancer patients. The recent development of linear scanners
      enables safe and accurate fine-needle aspiration (FNA) of mediastinal and upper
      abdominal structures under real-time ultrasound guidance. However, various
      methods and equipment for mediastinal EUS-FNA are being used throughout the
      world, and a detailed description of the procedures is lacking. A thorough
      description of linear EUS-FNA is needed. METHODS: A step-by-step description of
      the linear EUS-FNA procedure as performed in our hospital will be provided.
      Ultrasonographic landmarks will be shown on images. The procedure will be related
      to published literature, with a systematic literature search. RESULTS: EUS-FNA is
      an outpatient procedure under conscious sedation. The typical linear EUS-FNA
      procedure starts with examination of the retroperitoneal area. After this,
      systematic scanning of the mediastinum is performed at intervals of 1-2cm.
      Abnormalities are noted, and FNA of the abnormalities can be performed. Specimens
      are assessed for cellularity on-site. The entire procedure takes 45-60 min.
      CONCLUSIONS: EUS-FNA is minimally invasive, accurate, and fast. Anatomical areas
      can be reached that are inaccessible for cervical mediastinoscopy. EUS-FNA is
      useful for the staging of lung cancer or the assessment and diagnosis of
      abnormalities in the posterior mediastinum.

PMID- 15715185
TI  - Respiratory symptoms and obstructive pulmonary disease in a population aged over
      70 years.
AB  - STUDY QUESTION: What is the prevalence of respiratory symptoms and obstructive
      pulmonary disease by age, sex, and smoking history in a population aged 70 years
      and older? What is the association between selected comorbidities and obstructive
      pulmonary disease? PATIENTS AND METHODS: A questionnaire on respiratory symptoms
      and disease, selected comorbidities, and smoking history was mailed to a cross
      sectional, sex- and age-stratified, random sample of the population 70 years and
      older of Bergen, Norway. RESULTS: About 11% of these elderly persons reported
      having at least one current obstructive pulmonary disease, 8% reported daily
      wheezing, and 12% reported significant dyspnea. The only respiratory symptom or
      disorder to show any clear age-related pattern was dyspnea, which increased
      through age 89 before declining. Dyspnea, current asthma, and current chronic
      bronchitis were about half as likely in males as females, after adjusting for
      smoking pack-years. Persons with obstructive pulmonary disease reported problems
      with walking, heart disease, and muscle/joint disease more frequently than those
      without. CONCLUSIONS: The prevalence of respiratory symptoms and obstructive
      pulmonary disease has been estimated. Only dyspnea was associated with age in
      this elderly population. Female sex was a predictor of dyspnea, current asthma,
      and current chronic bronchitis.

PMID- 15715186
TI  - Does consumption of ethanol distort measurements of exhaled nitric oxide?
AB  - BACKGROUND: Measuring FE(NO) is a novel and non-invasive way to monitor airway
      inflammation (e.g. asthma). This clinical study was designed to investigate
      whether drinking ethanol might distort FE(NO) measurements. METHODS: Twenty
      healthy subjects drank 0.40 g ethanol/kg body weight in 15 min. Measurement of
      FE(NO) started approximately 30 min before drinking and at various times
      afterwards for 4 h post-dosing. Ethanol concentrations were determined in venous
      blood by gas chromatography and in end-exhaled breath by infra-red spectrometry.
      RESULTS: The within subject standard deviation for determination of FE(NO) was
      1.3 ppb, corresponding to a CV of 7.7%. The mean change in FE(NO) from pre
      drinking levels during the 4h testing was statistically significant (P<0.001)
      according to repeated measures ANOVA. In absolute units the mean change was
      small, -2.01 and -1.94 ppb at 3 and 4h post-dosing, respectively (P<0.013,
      P<0.005). CONCLUSIONS: FE(NO) measurements were reproducible even in subjects
      with moderate concentrations of ethanol in blood and breath. The small decrease
      in FE(NO) observed at 3 and 4 h post-drinking was less than the intra-subject
      variations in FE(NO) measurements. The breath-alcohol concentrations in this
      study exceed all other endogenous volatiles, thus making it unlikely that other
      substances in human breath will bias the FE(NO) measurements.

PMID- 15715187
TI  - Increase in airway neutrophils after oral but not inhaled corticosteroid therapy
      in mild asthma.
AB  - BACKGROUND: Neutrophils, in addition to eosinophils, are prominent in the airways
      of patients with severe asthma who are usually on long-term oral and inhaled
      corticosteroid treatment. We determined whether inhaled or oral corticosteroid
      therapy can induce airway neutrophilia. METHODS: We performed two separate
      placebo-controlled studies in which patients with mild asthma were treated with
      either prednisolone (30mg per day for 7 days; n = 9) or placebo tablets (n = 8),
      or with either inhaled budesonide (800 microg twice daily for 4 weeks; n = 6) or
      inhaled placebo (n = 6). Fiberoptic bronchoscopy was performed before treatment
      and at day 7 of oral treatment, and at day 28 of inhaled therapy. Bronchial
      sections were immunostained with an antibody to major basic protein for
      eosinophils, and with an antibody to neutrophil elastase for neutrophils. Induced
      sputum was obtained in the prednisolone study. RESULTS: Neutrophils in airway
      submucosa increased after prednisolone from median 76 to 140/mm2 (P = 0.05); this
      change was higher than that after placebo (P = 0.04). Eosinophils decreased from
      24 to 9/mm2 (P = 0.03), but this was not significantly different from placebo.
      Eosinophils and neutrophils, and levels of IL-8 and myeloperoxidase in induced
      sputum did not change after prednisolone. There was no change in neutrophil
      counts after budesonide, but the reduction in eosinophils was greater than
      placebo (P = 0.05). Budesonide improved bronchial responsiveness, but
      prednisolone did not. CONCLUSION: Corticosteroid therapy by the oral but not
      inhaled route can induce neutrophil recruitment into the airways of patients with
      mild asthma. This could explain the increase in airway neutrophils observed in
      severe asthmatics treated with oral corticosteroids.

PMID- 15715188
TI  - The effect of oral clarithromycin on health status and sputum bacteriology in
      stable COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by
      airway inflammation, poor health status and recurrent infective exacerbations.
      Macrolide antibiotics have been shown to improve symptoms and exacerbation rate
      in chronic lung disease, particularly cystic fibrosis (CF) and diffuse pan
      bronchiolitis. The effect of long-term oral clarithromycin on health status,
      sputum bacterial numbers and exacerbation rate in subjects with clinically stable
      COPD is undetermined. METHODS: Subjects with moderate-to-severe COPD were
      recruited into a prospective, double-blind, randomised-controlled trial of 3
      months oral clarithromycin (Klaricid XL) or placebo once-daily. The effect of
      clarithromycin on health status (St. George respiratory and Short Form-36
      questionnaires), sputum quantitative bacterial numbers and exacerbation rate were
      investigated. RESULTS: Sixty-seven subjects (46 males) were recruited; 31 and 36
      subjects received clarithromycin and placebo, respectively. There were 7(10%)
      withdrawals. Compared to placebo, clarithromycin did not significantly improve
      health status, sputum bacterial numbers, or exacerbation rate. CONCLUSIONS: Three
      months of oral clarithromycin given to subjects with stable COPD does not improve
      health status, sputum bacterial numbers or exacerbation rate. Treatment of COPD
      with clarithromycin during the clinical stable state yields no clinical
      advantages and therefore cannot be recommended as means of eliminating sputum
      bacteria or preventing infective exacerbations.

PMID- 15715189
TI  - RANTES G-401A polymorphism is associated with allergen sensitization and FEV1 in
      Chinese children.
AB  - G-401A polymorphism in RANTES promoter was associated with near-fatal asthma and
      atopic dermatitis in children. We studied whether gain-of-function mutations in
      RANTES gene were associated with asthma and atopy-related traits in Chinese
      children. Plasma total and aeroallergen-specific IgE concentrations were measured
      using micro-particle immunoassay and fluorescent enzyme immunoassay,
      respectively. Restriction fragment length polymorphism was used to genotype
      RANTES G-401A and C-28G. One hundred and twenty-nine asthmatic children and 66
      controls were recruited. Their mean logarithmic plasma total IgE concentrations
      were 2.53 and 1.98, respectively (P<0.0001). RANTES G-401A was not associated
      with physician-diagnosed asthma (P = 0.408). However, RANTES G-401A allele was
      significantly associated with IgE sensitization to cat (odds ratio 2.35; 95% CI
      1.15-4.77; P = 0.010). Those homozygous for -401A had higher plasma cat-specific
      IgE levels (P = 0.034). Subjects having -401A were also more likely to have mold
      specific IgE (odds ratio 3.82; 95% CI 1.24-12.14; P = 0.007). On spirometry,
      those with -401A/ A had lower forced expiratory volume in 1-s (FEV1; P = 0.044).
      RANTES C-28G was not associated with any outcome in this study. In conclusion,
      the gain-of-function mutation at -401 of RANTES promoter is associated with
      sensitization to cat and mold allergens and FEV1 in Chinese children.

PMID- 15715190
TI  - Premedication for bronchoscopy in older patients: a double-blind comparison of
      two regimens.
AB  - INTRODUCTION: Older patients are the most prevalent age cohort requiring
      bronchoscopy. Prior sedation should be offered to improve patient comfort and
      operator technical ease. Older patients have increased sensitivity to centrally
      acting drugs increasing the procedural risk. This perceived risk may limit access
      to bronchoscopy in older patients. There have been no systematic prospective
      placebo-controlled studies in older patients. We compared a novel premedication
      regimen-oral temazepam plus nebulised Lignocaine (new treatment) to an
      established regimen of intravenous alfentanyl (control). METHODS: Consecutive
      patients 75 years and older referred for bronchoscopy were considered. Twenty
      five patients were randomly assigned to each group. The primary outcome measure
      was the lowest oxygen saturation recorded from the administration of IV drugs and
      for 30 min post-bronchoscopy. RESULTS: The lowest mean oxygen saturation in the
      new treatment group was 92.2% (90.3-94.2) and in the control group 91.1% (89.2
      93.1). This was not statistically different (P = 0.370). There were no adverse
      events. CONCLUSION: This is the largest prospective study to date on an older
      population undergoing bronchoscopy supporting previous retrospective findings
      regarding the safety of this procedure. Determined by oxygen saturations there is
      no difference in safety between premedication regimens comprising oral
      temazepam/nebulised lignocaine or intravenous alfentanyl.

PMID- 15715191
TI  - The effect of pet ownership on the risk of allergic sensitisation and bronchial
      asthma.
AB  - An increasing volume of evidence suggests that early contact of children with the
      allergens of furred pets (especially those produced by cats) may determine a
      lower risk of developing allergic sensitisation to these materials. A possible
      explanation of this data is that an early inhalation of high levels of the major
      cat allergen Fel d 1 induces the production of IgG and IgG4 antibodies with a
      "protective" effect. Other authors have shown that the prevalence of allergic
      sensitisation to cats, in adults, is reduced in those patients exposed to the
      lowest and highest levels of the allergens. On the contrary, the risk of
      developing sensitisation to cats is significantly higher when the patients were
      exposed to intermediate levels of Fel d 1. Moreover, epidemiological studies have
      demonstrated a relatively low prevalence of cat allergy (about 10%) in some
      countries where rates of cat ownership are high. This data confirms the role of
      indirect exposure to pet allergens in inducing allergic sensitisation. Clothes of
      pet owners have been indicated as the carriers for the dispersal of these
      allergens in pet-free environments. However, it is important to point out that
      exposure of highly sensitised patients to relevant amounts of pet allergens (such
      as in a pet shows/shops) may determine a dramatic exacerbation of nasal and/or
      bronchial symptoms.

PMID- 15715192
TI  - Idiopathic non-specific interstitial pneumonia: as an "autoimmune interstitial
      pneumonia".
AB  - Recently, we have experienced significant number of patients diagnosed with non
      specific interstitial pneumonia (NSIP) by open lung biopsy or video-assisted
      thoracoscopic surgery. The purpose of this study is to compare clinical and
      pathological features of idiopathic NSIP and NSIP associated with underlying
      diseases (mainly autoimmune disorders). Forty-six patients with histologically
      proven NSIP were retrospectively collected. Twenty-four patients had underlying
      diseases (12 polymyositis/dermatomyositis, 5 systemic sclerosis, 2 rheumatoid
      arthritis, 2 Sjogren's syndrome, 1 ulcerative colitis, 1 primary biliary
      cirrhosis, and 1 multiple myeloma). Twenty-two of the 46 patients had no
      underlying diseases. It was very difficult to distinguish idiopathic NSIP and
      NSIP associated with underlying diseases, clinically and radiologically.
      Pathologically, Lymphocytic pneumonitis was demonstrated in both groups, and it
      was impossible to distinguish idiopathic NSIP and NSIP associated with underlying
      diseases. Since generalized symptoms were not observed in patients with
      idiopathic NSIP, and clinical and pathological features were identical to NSIP
      with several autoimmune disorders, we postulate new clinical entities of
      "autoimmune interstitial pneumonia" in cases without underlying diseases.

PMID- 15715193
TI  - The interrelationship between markers of inflammation and oxidative stress in
      chronic obstructive pulmonary disease: modulation by inhaled steroids and
      antioxidant.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is accompanied by both
      airway and systemic inflammation and by oxidative stress. This study aimed to
      characterise the relationship between oxidative stress and inflammatory
      components in induced sputum and blood. MATERIAL & METHODS: We studied blood and
      sputum samples from stable COPD patients (mean FEV1 60.5+/-7.5% predicted) at
      baseline (no treatment) and after 10 weeks treatment with either inhaled steroid,
      fluticasone propionate (FP) (1000 microg/d) or 10 weeks treatment with N
      acetylcysteine (600mg/d) (NAC). We assessed the inflammatory markers (IL-8, ECP,
      sICAM-1, NE) in sputum and serum and we compared them with blood markers of
      oxidative stress (SOD, GPx, TEAC, albumin, vitamin E and A). RESULTS: At baseline
      blood sICAM-1 correlated with IL-8 levels (P<0.01, r = 0.62) and negatively with
      GPx (P<0.01, r = -0.63) and with TEAC (P<0.05, r = -0.53). TEAC correlated
      positively with GPx (P<0.01, r = 0.70). Correlation between sICAM and IL-8
      disappeared after NAC treatment. The correlation between sICAM and GPx
      disappeared after FP treatment. The correlation between TEAC and GPx was
      maintained after both NAC and FP. CONCLUSIONS: The relationship between markers
      of inflammation, adhesion and antioxidant capacity is significantly modulated by
      treatment with N-acetylcysteine or inhaled corticosteroids.

PMID- 15715194
TI  - Close temporal association of bronchial asthma and ischemic colitis--case report
      and review of the literature.
AB  - We report a case of ischemic colitis in an elderly male who had initially
      presented with acute asthma exacerbation. The clinical course of hospitalization,
      surgical and pathological findings were described. We review three previously
      reported cases of ischemic colitis and bronchial asthma and explore possible
      mechanisms to explain this association. The complex interaction of smooth muscle
      tone and autonomic nervous system in the etiopathogenesis of bronchial asthma and
      ischemic colitis is discussed. Further studies should be undertaken to clarify
      this association.

PMID- 15715195
TI  - Perfluoroarylazide derivatives of 2'-O-modified oligoribonucleotides: efficient
      reagents for RNA photomodification.
AB  - Site-specific photomodification of the 5'-terminal fragment of MDR1 mRNA by
      perfluoroarylazide derivatives of 2'-O-modified (2'-O-methyl or 2'-O
      tetrahydropyranyl) oligoribo- and oligodeoxyribonucleotides was investigated. The
      conjugates built of 2'-O-modified oligoribonucleotides demonstrate beneficial
      features compared with their deoxyribo analogs: the extent of RNA modification by
      2'-O-modified oligoribonucleotides and oligodeoxyribonucleotide conjugates was 40
      50% and 20%, respectively.

PMID- 15715196
TI  - Synthesis and DNA topoisomerase-II inhibitory activity of unnatural nucleosides.
AB  - The synthesis and biological activities of a number of unnatural nucleosides (23
      43) is described. Nucleosides have been synthesized by SnCl4-catalyzed
      condensation of amino sugar acetates and silylated modified pyrimidines. Few of
      the 2'-O-acetyl derivatives of the nucleosides were hydrolyzed to the respective
      hydroxy derivatives by treatment with methanol saturated with ammonia. The
      compounds were screened against Filarial DNA-topoisomerase-II but only one of the
      compounds (29) inhibited this enzyme at 40 microg/mL of reaction mixture.

PMID- 15715197
TI  - Acyclic nucleosides bearing a furanyl scaffold.
AB  - Synthesis of acyclic nucleosides bearing a furanyl scaffold is described. The
      approach involved the construction of the base moiety onto a dihydrofuranyl
      intermediate. While the A and C analogues did exhibit some substrate activity
      toward deoxycytidine kinase, the compounds were devoid of any significant anti
      HIV activity.

PMID- 15715198
TI  - Synthesis and biological evaluation of 2- and 7-substituted 9-deazaadenosine
      analogues.
AB  - A series of 2-halogen and 7-alkyl substituted analogues of 9-deazaadenosine and
      2'-deoxy-9-deazaadenosine was synthesized by new efficient methodology involving
      transformation of corresponding 9-deazaguanosine and 2'-deoxyguanosine, which in
      turn were synthesized by direct C-glycosylation of 1-benzyl-9-deazaguanine with 1
      O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose and methyl 2-deoxy-3,5-di-O-(p
      toluoyl)-D-ribofuranoside, respectively. Deoxychlorination of C6 and
      diazotization/chloroor fluoro-dediazoniation of the sugar-protected 9
      deazaguanosine, followed by selective ammonolysis at C6 and deprotection of the
      sugar moiety, gave 2-chloro- and 2-fluoro-9-deazaadenosine (6 and 9).
      Substitution of the 7-position of the dihalogen-intermediate with alkyl groups,
      followed by ammonolysis and deprotection, provided 2-chloro-7-alkyl-9
      deazaadenosines (13a-e) and 2-fluoro-7-benzyl-9-deazaadenosine (13f). Catalytic
      hydrogenation of 13a-e gave 7-alkyl-9-deazaadenosines 14a-e. Similarly, 2-chloro
      2'-deoxy-9-deazaadenosine (21), 2-chloro-2'-deoxy-7-methyl-9-deazaadenosine (25),
      2'-deoxy-9-deazaadenosine (22), and 2'-deoxy-7-methyl-9-deazaadenosine (26) were
      prepared from sugar-protected 2'-deoxy-9-deazaguanosine. Among these compounds, 7
      benzyl-9-deazaadenosine (14b) showed the most potent cytotoxic activity, with
      IC50 values of 0.07, 0.1, 0.2 and 1.5 microM, while both 7-methyl-9
      deazaadenosine (14a) and 2-fluoro-9-deazaadenosine (9) also demonstrated
      significant cytotoxic activity with IC50 values of 0.4, 0.7, 0.3, and 1.5 microM,
      and 1.5, 0.9, 0.3, and 5 microM against L 1210 leukemia, P388 leukemia, CCRF-CEM
      lymphoblastic leukemia, and B16F10 melanoma cells, respectively.

PMID- 15715199
TI  - Synthesis and anti-HCMV activity of novel 2',3', 4'-trimethyl branched
      carbocyclic nucleosides.
AB  - This article reports the synthesis of novel 2',3',4'-trimethyl branched
      carbocyclic nucleosides. The introduction of a methyl group in the 2' and 3'
      position was accomplished by sequential Horner-Wadsworth-Emmons reaction and
      isopropenyl magnesiumbromide addition, respectively. The construction of the 4'
      quaternary carbon needed was carried out using a [3,3]-sigmatropic rearrangement.
      Bis-vinyls were successfully cyclized using a Grubbs catalyst II. The natural
      bases (adenine, cytosine) were efficiently coupled with the use of a Pd(O)
      catalyst.

PMID- 15715200
TI  - State and certifying boards/associations: CE and competency requirements.

PMID- 15715201
TI  - Education: key to the Magnet culture.

PMID- 15715202
TI  - An overview of congenital long QT syndrome.

PMID- 15715203
TI  - Keeping participants enrolled: use of anticipation.

PMID- 15715204
TI  - Influences of patient behavior on clinical nurses' pain assessment: implications
      for continuing education.
AB  - Pain management is an important consideration in the promotion of patients'
      comfort. However, research continues to indicate patients' pain management is
      poor. The nursing literature cites nurses' lack of knowledge as a significant
      determinant of poor pain management practices. The impetus for this study arose
      from poor attendance by nurses at inservice sessions discussing pain assessment
      and management. Knowledge of existing nursing practice and accompanying beliefs
      and attitudes in relation to pain management is paramount in the development of
      relevant continuing education for registered nurses. The aim of this
      investigation was to study nurses' intention to treat pain in different patients.
      A 10-page questionnaire with eight different patient scenarios was distributed to
      886 nurses across all clinical divisions of an acute tertiary facility. Results
      indicate knowledge deficits regarding optimum pain relief for patients. This
      article highlights the need for innovative teaching strategies and approaches in
      the clinical context to heighten nurses' awareness of their lack of knowledge of
      pain assessment and management.

PMID- 15715205
TI  - Teaching teachers to teach with technology.
AB  - As the local and national shortage of nursing faculty grew, the Washington State
      University College of Nursing revised and expanded their nursing education
      courses in a technologically intense pilot program. Reflections on all phases of
      the planning, implementation, and evaluation of the first course in this program
      are described as lessons learned with implications for future nursing education
      and research endeavors.

PMID- 15715206
TI  - Online education: needs assessment for faculty development.
AB  - The rapidly evolving paradigm of technology-based education has increased the
      number of faculty teaching online. The role of faculty has changed from the
      traditional classroom instruction format to an online community of learning.
      Therefore, faculty development in online education becomes a critical component
      during this transitional period. A survey of faculty of the College of Applied
      Science and Technology in a midwestern university was conducted to identify their
      level of perceived expertise in online teaching and the priorities of areas to be
      addressed in faculty development sessions. Benner's five-stage sequential
      transformation from novice to expert was used to construct the questionnaire.
      Results showed that faculty who taught online perceived their level of expertise
      to range from advanced beginner to competent, whereas faculty who had not taught
      online were at the novice and advanced beginner levels. Redesigning and
      rethinking faculty roles emerged as the number one priority area to be addressed
      in continuing education sessions. Implications for faculty development for online
      education sessions are presented.

PMID- 15715207
TI  - National quality efforts: what continuing and staff development educators need to
      know.
AB  - In 1994, the American Nurses Association initiated a series of activities
      currently referred to as Nursing's Quality Initiative. This first step toward
      public accountability was based on the premise that all nurses must become more
      knowledgeable about the measurement, improvement, and benchmarking of clinical
      costs, quality, and outcomes specific to nursing. The American Nurses Association
      has not been working alone to advance quality health care. Rather, it has taken
      an active role in several collaborative activities, including those of the
      National Quality Forum. The National Quality Forum has focused on a variety of
      issues, including nursing care performance measurement, an activity in which the
      American Nurses Association has been involved. It is up to professional nursing,
      the National Quality Forum, and all who have interest in the provision (or
      receipt) of quality health care to advance quality in a collaborative,
      coordinated way.

PMID- 15715208
TI  - Presidential address. Classical is critical: alleviating the burden of parasitic
      diseases.

PMID- 15715209
TI  - Acceptance of the Clark P. Read Mentor Award: a privileged life: lessons learned-
      lessons given.

PMID- 15715210
TI  - Acceptance of the 2004 Henry Baldwin Ward medal.

PMID- 15715211
TI  - Rapid age-related changes in infection behavior of entomopathogenic nematodes.
AB  - Nonfeeding infective juvenile (IJ) entomopathogenic nematodes (EPNs) are used as
      biological agents to control soil-dwelling insects, but poor storage stability
      remains an obstacle to their widespread acceptance by distributors and growers as
      well as a frustration to researchers. Age is one factor contributing to
      variability in EPN efficacy. We hypothesized that age effects on the
      infectiousness of IJs would be evident within the length of time necessary for
      IJs to infect a host. The penetration behavior of "young" (<1-wk-old) and "old"
      (2- to 4-wk-old) Heterorhabditis bacteriophora (GPS 11 strain), Steinernema
      carpocapsae (All strain), and Steinernema feltiae (UK strain) IJs was evaluated
      during 5 "exposure periods" to the larvae of the wax moth, Galleria mellonella.
      Individual larvae were exposed to nematode-infested soil for exposure periods of
      4, 8, 16, 32, and 64 hr. Cadavers were dissected after 72 hr, and the IJs that
      penetrated the larvae were counted. Larval mortality did not differ significantly
      between 72- and 144-hr "observation periods," or points at which larval mortality
      was noted, for any age class or species. However, age and species effects were
      noted in G. mellonella mortality and nematode penetration during shorter time
      periods. Initial mortality caused by S. carpocapsae and H. bacteriophora IJs
      declined with nematode age but increased with S. feltiae IJ age. Young S.
      carpocapsae IJs penetrated G. mellonella larvae at higher rates than old members
      of the species (27-45% vs. 1-4%). Conversely, old S. feltiae IJs had higher
      penetration rates than young IJs (approximately 8 to 57% vs. 4 to approximately
      31%), whereas H. bacteriophora IJs had very low penetration rates regardless of
      age (3-5.6%). Our results show that the effect of age on IJ infectiousness can be
      detected in IJs aged only 2 wk by a 4-hr exposure period to G. mellonella. These
      results have important implications for storage and application of EPNs and
      suggest the possibility of shortening the time required to detect nematodes in
      the soil.

PMID- 15715212
TI  - Molecular mechanisms involved in the differential effects of sex steroids on the
      reproduction and infectivity of Taenia crassiceps.
AB  - The in vitro exposure of Taenia crassiceps cysticerci to 17-beta estradiol (E2)
      and progesterone (P4) stimulated their reproduction and infectivity. Testosterone
      (T4) and dihydrotestosterone (DHT) inhibited their reproduction and reduced their
      motility and infectivity. E2 and P4 increased, whereas T4 and DHT reduced, the
      expression of parasite c-fos and c-jun and DNA synthesis. In vitro exposure of
      cysticerci to sex steroids before their inoculation into recipient noninfected
      mice resulted in large parasite loads when pretreated with E2 and P4 and in
      smaller loads when pretreated with T4 and DHT To determine the possible molecular
      mechanisms by which sex steroids affect T. crassiceps, sex steroid receptors were
      amplified. Taenia crassiceps expressed estrogen receptors (both alpha and beta
      isoforms) and androgen receptors but no P4 receptors. These results demonstrate
      that sex steroids act directly on parasite reproduction by binding to a classic
      and specific sex steroid receptor on the parasite. The differential response of
      cysticerci to sex steroids may also be involved in their ability to grow faster
      in the murine female or feminized male host. This is the first report of direct
      sex steroid effects on the parasite possibly through sex steroid receptors in the
      cysticerci.

PMID- 15715213
TI  - Analysis of transcripts expressed by Eimeria tenella oocysts using subtractive
      hybridization methods.
AB  - To characterize the genes expressed by Eimeria tenella oocysts, the sequence of
      499 expressed sequence tags (ESTs) was obtained from complementary DNA (cDNAs)
      enriched for transcripts expressed by unsporulated or sporulated oocysts. Of
      these, 225 clones were isolated from cDNA of sporulated oocysts and 274 from
      unsporulated oocysts. A total of 163 unique sequences were found, and the
      majority of these (64%) represent novel genes with no significant homology to the
      proteins in GenBank. Approximately half of the unique transcripts generated from
      sporulated oocysts are also expressed by sporozoites and merozoites, whereas the
      expression of most (79%) of the transcripts from unsporulated oocysts has not yet
      been detected at other stages of development. The expression of 4 transcripts
      obtained from the subtracted cDNAs was confirmed by quantitative reverse
      transcriptase-polymerase chain reaction. The results confirmed that these
      transcripts are in fact differentially expressed between sporulated and
      unsporulated oocysts.

PMID- 15715214
TI  - A comparative approach to understanding causes and consequences of mollusc
      digenean size relationships: a case study with Allocreadiid trematodes and
      Cyclocalyx clams.
AB  - Allocreadiid flukes often parasitize and castrate sphaeriid freshwater clams. The
      effects of parasitic castrators on host population life history can lead to
      earlier reproductive onset, changes in body size, or changes in the number of
      reproductive events per year. However, little is known about whether species- or
      clade-level traits are associated with parasite prevalence. In this study, we
      examine if phenotypic effects, e.g., size change, seen at the population level,
      sort to the species or clade level. To answer this question, we determined if
      different-sized host species in the ecologically important, widespread, and
      common sphaeriid subgenus Cyclocalyx have different prevalences of allocreadiid
      infection. After showing that large species are more than 12 times more likely to
      have patent infections than small species, we examined the evolution of size
      within Cyclocalyx lineages. Transitions from large size to small size or vice
      versa have occurred at least twice and probably many times during lineage
      diversification, perhaps relating to trade-offs between clutch size and parasite
      risk. Finally, based on existing data, we show that it is unlikely that age and
      body size are correlated; therefore, a simple age-exposure model is not a
      sufficient explanation for parasite prevalence in this clade.

PMID- 15715215
TI  - A comparison of the intestinal helminth communities of Equidae in Southern
      Africa.
AB  - The intestinal helminth communities of 8 horses, 12 donkeys, 21 Hartmann's
      mountain zebras, and 44 Burchell's zebras were compared using the original data
      from 6 studies in South Africa and Namibia. Necropsy and worm recovery techniques
      were comparable between the studies. Sixty helminth species (58 nematode, 1
      cestode, and 1 trematode species) were recorded. There were significant
      differences in the helminth community structures of the 4 Equus species. The
      helminth communities of the 2 closely related zebra subspecies were most similar,
      and they jointly shared 7 helminth species with donkeys and only 1 with horses.
      Geographic variation and host-mixing contributed to the helminth species
      composition. Multiple confamilial species infections were the norm in the donkeys
      and zebra subspecies, and no single-species infection was recorded for the
      Strongylidae. Congeneric species were commonly recorded in 3 genera
      (Cyathostomum, Cylicocyclus, and Cylicostephanus). The shape of the occupancy
      frequency distributions for the donkeys and zebra subspecies was multimodal, with
      no clear satellite or core modes. Despite the presence of environmental
      variability and comparatively low parasite-host specificity, the phylogenetic
      signal within Equus helminth communities remains strong.

PMID- 15715216
TI  - Ectoparasite and hemoparasite infection in a diverse temperate lizard assemblage
      at Macraes Flat, South Island, New Zealand.
AB  - A lizard assemblage at Macraes Flat, New Zealand, comprising the common skinks
      Oligosoma maccanni and Oligosoma nigriplantare polychroma, the endangered species
      Oligosoma grande and Oligosoma otagense, and the common gecko Hoplodactylus
      maculatus, was studied to determine the prevalence of ectoparasites and
      hemoparasites. The mites Odontacarus lygosomae and Ophionyssus scincorum infected
      all Oligosoma spp. only, and the mite Neotrombicula naultini infected only H.
      maculatus. The hemoparasite Hepatozoon lygosomarum infected all Oligosoma skinks,
      except O. n. polychroma. Oligosoma otagense had the highest infection levels of
      all parasites by several orders of magnitude. For all lizard species, there was
      no difference in mite prevalence between adult males and adult females, but
      juveniles were less often infected. For all skink species, there was a
      significant relationship between presence of the hemoparasite He. lygosomarum and
      infection intensity of the supposed vector, O. scincorum. It is unclear if
      patterns of parasite infection reflect species-specific susceptibility, host
      parasite species-specific spatial ecology, or environmentally induced host
      physiological impairment. Considering the threatened nature of O. otagense,
      evidence of high parasitemia should stimulate further investigation.

PMID- 15715217
TI  - Transition models to assess risk factors for new and persistent trypanosome
      infections in cattle-analysis of longitudinal data from the Ghibe Valley,
      southwest Ethiopia.
AB  - The objective of this study was to apply transition models to distinguish between
      factors associated with both incident and persistent trypanosome infections. Data
      collected from 1561 cattle were analyzed from a long-term study involving 8 herds
      in which both trypanosome infections (a total of 56,931 cattle sampling-months)
      and tsetse (Glossina spp.) challenge were monitored monthly from March 1986 to
      March 1998. Both pour-on and insecticide-target tsetse control programs and mass
      treatment with diminazene aceturate before tsetse control were associated with
      significant decreases in both incidence and persistence of trypanosome infection
      relative to noncontrol periods, as were seasonal and sex effects. The magnitudes
      of the effects were, however, often different for new and persistent infections.
      For persistence of infection, there were 2 trends. In general, the duration of
      infection increased during the study, despite the regular treatment with
      diminazene aceturate. The transition model had 2 major benefits. The first was to
      identify an increasing duration of infections with time, taking into account
      other factors associated with increasing infection risk. The second was to
      highlight different patterns in the effects of certain factors on new and
      persistent trypanosome infections.

PMID- 15715218
TI  - Sarcotretes (Copepoda: Pennellidae) parasitizing myctophid fishes in the Southern
      Ocean: new information from seabird diet.
AB  - Copepods are common parasites of marine fishes, but little information is
      available on the biology of species that parasitize mesopelagic fishes in oceanic
      waters. In this study, we report the finding of large numbers of Sarcotretes spp.
      (n = 2340) in dietary samples of king penguins collected at Crozet and the
      Falklands Islands. Analysis of penguin food indicates that S. scopeli Jungersen
      parasitizes myctophid fishes, Protomyctophum tenisoni (Norman), in the southern
      Indian Ocean and P. choriodon Hulley in the southern Atlantic. It suggests that
      the much rarer S. eristaliformis (Brian) also parasitizes myctophids, but the
      host species of that copepod remains to be determined. The new data add
      significant information concerning the hosts and distribution of Sarcotretes spp.
      in the Southern Ocean and emphasize the usefulness of ichthyophagous predators in
      revealing valuable information on the biology of organisms that parasitize their
      prey.

PMID- 15715219
TI  - Ectoparasites and other epifaunistic arthropods of sympatric cotton mice and
      golden mice: comparisons and implications for vector-borne zoonotic diseases.
AB  - Ectoparasite and epifaunistic arthropod biodiversity and infestation parameters
      were compared between 2 sympatric small rodent species, the cotton mouse
      (Peromyscus gossypinus (Le Conte)) and golden mouse (Ochrotomys nuttalli
      (Harlan)), in southern Georgia from 1992 to 2003. Because the cotton mouse is
      known to be a reservoir of more vector-borne zoonotic pathogens than the golden
      mouse, we hypothesized that it would be parasitized by more ectoparasites that
      are known to be vectors of these pathogens. Cotton mice (n = 202) were
      parasitized by 19 species of arthropods, whereas golden mice (n = 46) were
      parasitized by 12 species. Eleven species of arthropods were recovered from both
      host species, whereas 7 were recorded only from cotton mice, and 1 species only
      from golden mice. Infestation prevalences (percent of mice parasitized) were
      significantly higher for 1 species of arthropod (the tropical rat mite
      Ornithonyssus bacoti (Hirst)) infesting cotton mice and for 4 species (the flea
      Peromyscopsylla scotti Fox and the mites Glycyphagus hypudaei Koch, Androlaelaps
      casalis (Berlese), and Androlaelaps fahrenholzi (Berlese)) infesting golden mice.
      Mean intensities (mean per infested mouse) were significantly higher for 2
      species (the flea Orchopeas leucopus (Baker) and the blacklegged tick Ixodes
      scapularis Say) infesting cotton mice and for 2 species (G. hypudaei and A.
      fahrenholzi) infesting golden mice. Ectoparasites that are known to be vectors of
      zoonotic pathogens were significantly more common on cotton mice than on golden
      mice. These ectoparasites included the rhopalopsyllid flea Polygenis gwyni (Fox),
      a vector of the agent of murine typhus; I. scapularis, the principal vector of
      the agents of Lyme borreliosis, human granulocytic ehrlichiosis, and human
      babesiosis; and O. bacoti, a laboratory vector of several zoonotic pathogens.
      However, 2 species of ixodid ticks that can transmit zoonotic pathogens were
      recovered from both host species. These were the American dog tick Dermacentor
      variabilis (Say), the principal vector of the agent of Rocky Mountain spotted
      fever in eastern North America, and Ixodes minor Neumann, an enzootic vector of
      the agent of Lyme borreliosis. Overall, the cotton mouse was parasitized by
      significantly more ectoparasites that are known to be vectors of zoonotic
      pathogens than was the golden mouse. These data support the hypothesis that the
      cotton mouse has greater epidemiological importance for zoonotic vector-borne
      pathogen transmission than does the golden mouse.

PMID- 15715220
TI  - Molecular characterization of Borrelia isolates from ticks and mammals from the
      southern United States.
AB  - Fifty Borrelia isolates from ticks and rodents from several geographic regions of
      the southern United States were analyzed by genomic macrorestriction analysis.
      Significant genetic diversity was observed among them. These isolates segregated
      into 4 major clusters and 10 subclusters, which are correlated with the
      genospecies distribution. Nineteen pulsed-field gel electrophoresis (PFGE) types
      were recognized among the isolates. The genospecies Borrelia andersonii and
      Borrelia bissettii consisted of 5 and 2 subclusters, respectively. Two
      subclusters comprised the Borrelia burgdorferi sensu stricto (s. s.) strains.
      These results indicated that PFGE is a suitable molecular typing method for B.
      burgdorferi at both the genospecies and strain levels. Seventeen representative
      isolates from different PFGE groups were analyzed by restriction fragment length
      polymorphism (RFLP) and sequence analysis of flaB. Twenty-three AluI, 3 CelII,
      and 11 DdeI RFLP patterns were found among strains from the B. burgdorferi sensu
      lato (s. l.) complex and the relapsing fever borreliae complex. Three genospecies
      in the B. burgdorferi s. l. complex and 1 species in the relapsing fever
      borreliae complex were recognized. Phylogenetic analysis based on nucleotide
      sequences of flaB indicated that all the Borrelia strains analyzed here could be
      divided into 2 parts, i.e., B. burgdorferi s. l. complex and the relapsing fever
      borreliae complex. The flaB appears to be a useful target gene to screen and
      identify strains from both B. burgdorferi s. l. and relapsing fever borreliae
      complexes.

PMID- 15715221
TI  - The origin of coelomocytes 5 and 6 and their interaction with a seam nurse cell
      in the free-living stages of Nippostrongylus brasiliensis.
AB  - A progenitor blast cell in the posterior of the newly hatched larva of
      Nippostrongylus brasiliensis yielded a large population of coelomic cells among
      which were 2 previously undiscovered coelomocytes, C5 and C6. The coelomocytes
      lay subdorsal and posterior to the genital primordium, C5 on the right and C6 on
      the left. Also, in the first-stage larva, 7 single seam cells appeared in the
      hypodermis on both the right and left sides arrayed in tandem along its length.
      Each seam cell (1-5, 7) went through 2 divisions with spaces maintained between
      the formed quartets. However, seam cell 6 underwent an unusual series of
      divisions resulting in the formation of a huge amoeboid nurse cell that enclosed
      a quartet of small cells in a vacuole; the quartet also was derived from seam
      cell 6. Ultimately, all the seam cells, including the nurse cells on each side of
      the larva, regressed and disappeared, except for the quartet cells, now released
      from their vacuole. These latter cells then remained dormant during the life of
      the free-living stages. During the process of seam cell development, coelomocytes
      5 and 6 aligned themselves closely to seam cells 6 and their progeny; some
      attached themselves to and even partially penetrated the nurse cells at the level
      of the vacuole. At the time of the second molt and the formation of the early
      third stage infective larva, tiny vesicles began to appear in the cytoplasm of
      coelomocytes 5 and 6. As vesicles increased in number, they aggregated into a
      mass at either the anterior or posterior pole of the cells. Coelomocytes 1-4
      situated anterior to the genital primordium differed from coelomocytes 5 and 6 in
      that they accumulated much larger numbers of vesicles that remained discrete in
      the cytoplasm and concentrated extraordinary amounts of vitamin B12 that was
      recognized as a red pigment filling the vesicles. However, no red pigment ever
      was seen in the vesicles of coelomocytes 5 and 6. On the basis of the very early
      sexual differentiation of larvae in the rat lung, it was determined that the
      infective free-living larvae from which they were derived, and which contained
      coelomocytes 5 and 6, were female; those lacking coelomocytes 5 and 6 were
      presumed to be male.

PMID- 15715222
TI  - A conserved 19-kDa Eimeria tenella antigen is a profilin-like protein.
AB  - A wide range of recombinant proteins from Eimeria species have been reported to
      offer some degree of protection against infection and disease, but the specific
      biological function of these proteins is largely unknown. Previous studies have
      demonstrated a 19-kDa protein of unknown function designated SZ-1 in sporozoites
      and merozoites of Eimeria acervulina that can be used to confer partial
      protection against coccidiosis. Reverse transcriptase-polymerase chain reaction
      indicated that the gene for SZ-1 is expressed by all the asexual stages of
      Eimeria tenella. Rabbit antisera to recombinant SZ-1 recognized an approximately
      19-kDa protein from extracts of E. tenella sporozoites, merozoites, sporulated
      oocysts, and oocysts in various stages of sporulation. Immunofluorescence
      antibody staining indicated specific staining of E. tenella sporozoites and
      merozoites. Staining was most intense in the cytoplasm of the posterior end of
      the parasite. The primary amino acid sequence of the gene for E. tenella SZ-1
      deduced from the E. tenella genome indicated a conserved domain for the actin
      regulatory protein profilin. A conserved binding site for poly-L-proline (PLP),
      characteristic of profilin was also observed. SZ-1 was separated from soluble
      extract of E. tenella proteins by affinity chromatography using a PLP ligand,
      confirming the ability of SZ-1 to bind PLP. SZ-1 also partially inhibited the
      polymerization of actin. The current results are consistent with the
      classification of SZ-1 as a profilin-related protein.

PMID- 15715223
TI  - The clearance of hidden cestode infection triggered by an independent activation
      of host defense in a teleost fish.
AB  - Parasites often elude effective recognition or attack (or both) by the host
      immune system, for example, though a tegument that possesses nonimmunogenic
      features. However, a general activation of host defense due to independent
      stimuli may increase immune activity to a level where such disguises are no
      longer effective, resulting in the clearance of an infection. We experimentally
      infected three-spined sticklebacks (Gasterosteus aculeatus) with the cestode
      Schistocephalus solidus. To independently foster a general immune response a few
      days later, we cut the tips of spines in some fish and sham-treated other fish.
      Cutting spines significantly reduced the prevalence of the infection. The injury
      evoked a physiological reaction that helped to clear a hidden parasite infection.

PMID- 15715224
TI  - Effects of copper sulfate toxicity on cercariae and metacercariae of Echinostoma
      caproni and Echinostoma trivolvis and on the survival of Biomphalaria glabrata
      snails.
AB  - Copper in the form of copper sulfate (CuSO4) decreases the survival of
      Biomphalaria glabrata snails, but the effects of this molluscicide on Echinostoma
      caproni and Echinostoma trivolvis, 2 species of digeneans that use B. glabrata as
      intermediate hosts, are not known. Studies were done on the effects of various
      concentrations of CuSO4 in artificial spring water (ASW) on the survival and
      infectivity of E. caproni and E. trivolvis cercariae. Solutions containing 1.0,
      0.1, and 0.01% CuSO4 were 100% lethal within 2 hr of exposure for both species.
      Time to 50% mortality in 0.001% CuSO4 was 8 hr for E. caproni and 16 hr for E.
      trivolvis; at 24 hr, the controls showed 50 and 65% mortality, respectively.
      Treatment of cercariae of both species for 0.5 hr in 0.001% CuSO4 had no effect
      on the ability of cercariae to form normal cysts in juvenile B. glabrata snails.
      However, treatment with 0.01% CuSO4 for 0.5 hr caused a significant reduction in
      the ability of cercariae of both species to encyst in snails. Treatment of
      encysted metacercariae of both species in 0.001% CuSO4 for I hr had no effect on
      subsequent excystation of these echinostomes in a trypsin-bile salts medium,
      whereas concentrations of 1.0, 0.1, and 0.01% CuSO4 and 1.0 and 0.1% CuSO4
      decreased chemical excystation of E. caproni and E. trivolvis cysts,
      respectively. Survival studies on the effects of CuSO4 in Locke's solution on
      chemically excysted metacercariae of both species were also done. Excysted
      metacercariae of both species were killed by 2 hr in either 0.1 or 0.01% CuSO4 in
      Locke's solution. However, time to 50% mortality for both species of excysted
      metacercariae in 0.001% CuSO4 was approximately 5 hr. Time to 50% mortality for
      the controls was about 12 hr. Survival of juvenile B. glabrata snails was also
      examined. All B. glabrata snails were dead by 6 hr in 1 and 0.1% CuSO4 in ASW.
      Biomphalaria glabrata snails showed 50% mortality by about 6 hr in 0.01% CuSO4
      and about 80% were still alive at 24 hr in 0.001% CuSO4. All controls were alive
      at 24 hr, at which time the experiment was terminated. Concentrations greater
      than 0.001% CuSO4 increased snail mortality, as well as that of the cercariae and
      excysted metacercariae of E. caproni and E. trivolvis. Our findings suggest that
      concentrations of copper sufficient to eliminate juvenile B. glabratta snails are
      also sufficient to kill the cercariae and excysted metacercariae of these
      digeneans but not the encysted metacercariae, which may be protected by their
      cyst walls.

PMID- 15715225
TI  - Occurrence of the internal parasite Portunion sp. (Isopoda: Entoniscidae) and its
      effect on reproduction in intertidal crabs (Decapoda: Grapsidae) from New
      Zealand.
AB  - The parasite fauna of 4 intertidal grapsid crabs from New Zealand was studied
      between 1998 and 2000. The occurrence of an undescribed entoniscid species,
      Portunion sp. (Isopoda: Epicaridea), is presented. Portunion sp. was found in
      Cyclograpsus lavauxi (34.1%, n = 1650), Hemigrapsus crenulatus (19.0%, n = 2300),
      and Helice crassa (11.6%, n = 825) but was absent from Hemigrapsus sexdentatus (n
      = 636). Parasitized hosts contained mostly 1 female Portunion sp. but
      occasionally up to 7 females were found. One to 3 dwarf males typically occurred
      on each mature female Portunion sp. Most developmental stages of female Portunion
      sp. were found throughout the year, demonstrating that reproduction and infection
      occurred continuously. Portunion sp. differentially affected male and female
      hosts. Prevalence was generally higher in male hosts than in female hosts and
      increased significantly with host size. Female hosts were castrated, whereas
      males were not. Portunion sp., therefore, influenced the operational sex ratio in
      its host species, causing a more male-biased ratio.

PMID- 15715226
TI  - Risk of transplacental transmission of Sarcocystis neurona and Neospora hughesi
      in California horses.
AB  - The study objective was to assess the risk of transplacental transmission of
      Sarcocystis neurona and Neospora hughesi in foals from 4 California farms during
      3 foaling seasons. Serum of presuckle foals and serum and colostrum of
      periparturient mares were tested using indirect fluorescent antibody tests for S.
      neurona and N. hughesi. Serum antibody titers were < or =10 in 366 presuckle
      foals tested. There was no serologic or histologic evidence of either parasite in
      aborted fetuses or placentas examined. Positivity for S. neurona and N. hughesi
      in mares increased with age. Mares < or =9 yr that originated from Kentucky were
      3.8 and 1.4 times more likely to be positive for S. neurona and N. hughesi,
      respectively, than mares from California. The strength of association between
      positivity to either parasite and state of birth decreased as age increased.
      Mares positive for S. neurona and N. hughesi were 2.2 and 1.7 times more likely,
      respectively, to have a previous abortion than negative mares, adjusted for age
      and state of birth. The annual mortality rate for mares was 4%. The annual
      incidence rate of equine protozoal myeloencephalitis was 0.2%. In conclusion,
      there was no detectable risk of transplacental transmission of S. neurona and N.
      hughesi. Prevalence of antibodies against both parasites in mares increased with
      age.

PMID- 15715227
TI  - Species composition of assemblages of Ceratomyxa (Myxozoa), parasites of lings
      Genypterus (Ophidiidae) in the southeastern Pacific Ocean: an ecomorphometric
      approach.
AB  - Studies on Myxozoa have emphasized their potential impact on aquatic animal
      health but less on ecological aspects. In this investigation, we assess the
      importance of host and latitudinal variations in the morphometry of spores of
      Ceratomyxa Theohan, 1892 (Myxozoa) from the gall bladder of 3 ling Genypterus
      (Pisces; Ophidiidae) species. Discriminant analyses indicated that several
      morphospecies of Ceratomyxa coexist in these hosts, despite the fact that the
      specific level of taxonomic resolution of each spore was not attempted. At least
      4 species, i.e., Ceratomyxa hokarari Meglitsch, 1960; Ceratomyxa inversa
      Meglitsch, 1960; Ceratomyxa laxa Meglitsch, 1960; and Ceratomyxa elongata
      Meglitsch, 1960 occur in the study area, and at least 2 species co-occur in each
      host and geographical location. The most widespread pattern found is that spores
      are larger in golden ling (Genypterus blacodes) and spore size decreases with
      increasing latitude; this may be associated with the species composition of these
      assemblages, as well as with the habitat and diet segregation of the host
      species.

PMID- 15715228
TI  - Gastrointestinal parasites of the guenons of western Uganda.
AB  - From January 1998 to December 2002, we collected 293 fecal samples from free
      ranging individuals of the 4 guenon species of western Uganda, i.e., redtail
      guenons (Cercopithecus ascanius), blue monkeys (Cercopithecus mitis), l'hoesti
      monkeys (Cercopithecus lhoesti), and vervet monkeys (Cercopithecus aethiops), to
      quantify the prevalence of gastrointestinal parasites. Helminth eggs, larvae, and
      protozoan cysts were isolated by sodium nitrate flotation and fecal
      sedimentation. Helminth parasites were identified, and infection prevalence was
      determined for all 4 guenon species. Coprocultures facilitated identification of
      strongylate nematodes. For the most common species, the redtail guenon, we
      documented prevalence of protozoan parasites and examined the effect of season
      and host sex on infection prevalence. Six nematodes (Strongyloidesfulleborni,
      Oesophagostomum sp., unidentified strongyle, Trichuris sp., Streptopharagus sp.,
      and Enterobius sp.), 1 cestode (Bertiella sp.), 1 trematode (Dicrocoeliidae), and
      5 protozoans (Entamoeba coli, Entamoeba histolytica, lodameoba butschlii, Giardia
      lamblia, and Chilomastix mesnili) were detected. Seasonal patterns of infection
      were not readily apparent for any parasite species infecting redtail guenons.
      Although prevalence never differed between male and female guenons, only adult
      females were infected with Oesophagostomum sp. and S. fulleborni.

PMID- 15715229
TI  - Transmission of Neospora caninum between wild and domestic animals.
AB  - To determine whether deer can transmit Neospora caninum, brains of naturally
      infected white-tailed deer (Odocoileus virginianus) were fed to 4 dogs; 2 of
      these dogs shed oocysts. Oocysts from 1 of the dogs were tested by polymerase
      chain reaction and found to be positive for N. caninum and negative for Hammondia
      heydorni. The internal transcribed spacer 1 sequence of the new strain
      (designated NC-deer1) was identical to N. caninum from domestic animals,
      indicating that N. caninum is transmitted between wild and domestic animals,
      often enough to prevent divergent evolution of isolated populations of the
      parasite. NC-deerl oocysts were administered to a calf that developed a high
      antibody titer, providing evidence that N. caninum from wildlife can infect
      cattle. In addition, N. caninum antibody seroprevalence was detected in 64/164
      (39%) free-ranging gray wolves (Canis lupus), 12/113 (11%) coyotes (Canis
      latrans), 50/193 (26%) white-tailed deer, and 8/61 (13%) moose (Alces alces).
      These data are consistent with a sylvatic transmission cycle of N. caninum
      between cervids and canids. We speculate that hunting by humans favors the
      transmission of N. caninum from deer to canids, because deer carcasses are
      usually eviscerated in the field. Infection of canids in turn increases the risk
      of transmitting the parasite to domestic livestock.

PMID- 15715230
TI  - Differential propagation of the metazoan parasite Myxobolus cerebralis by
      Limnodrilus hoffmeisteri, Ilyodrilus templetoni, and genetically distinct strains
      of Tubifex tubifex.
AB  - Whirling disease, caused by the parasite Myxobolus cerebralis, has infected
      rainbow trout (Oncorhynchus mykiss) and other salmonid fish in the western United
      States, often with devastating results to native populations but without a
      discernible spatial pattern. The parasite develops in a complex 2-host system in
      which the aquatic oligochaete Tubifex tubifex is an obligate host. Because
      substantial differences in whirling disease severity in different areas of North
      America did not seem explainable by environmental factors or features of the
      parasite or its fish host, we sought to determine whether ecological or genetic
      variation within oligochaete host populations may be responsible. We found large
      differences in compatibility between the parasite and various laboratory strains
      of T. tubifex that were established from geographic regions with different
      whirling disease histories. Moreover, 2 closely related species of tubificids,
      Limnodrilus hoffmeisteri and Ilyodrilus templetoni, which occur naturally in
      mixed species assemblages with T. tubifex, were incompatible with M. cerebralis.
      Virulence of the parasite was directly correlated with the numbers of
      triactinomyxon spores that developed within each strain of T. tubifex. Thus, the
      level of virulence was directly related to the compatibility between the host
      strain and the parasite. Genetic analyses revealed relationships that were in
      agreement with the level of parasite production. Differences in compatibilities
      between oligochaetes and M. cerebralis may contribute to the spatial variance in
      the severity of the disease among salmonid populations.

PMID- 15715231
TI  - Metazoan parasite fauna as a biological tag for the habitat of the flounder
      Hippoglossina macrops from northern Chile, in a depth gradient.
AB  - Quantitative changes in the parasite communities of the flounder Hippoglossina
      macrops (Steindachner) were studied along a depth gradient. Samples were obtained
      from the waters off Coquimbo, Chile (29 degrees 18'S to 30 degrees 50'S), at
      depths ranging from 160 to 342 m. Samples were assigned to 3 depths, i.e.,
      shallow water (less than 200 m), midwater (from 200 to 300 m), and deep water
      (more than 300 m). Twelve parasite species were recorded: Neoheterobothrium
      chilensis and Entobdella hippoglossi (Monogenea); Holobomolochus chilensis and
      Protochondria longicauda (Copepoda); Gliptonobdella sp. (Hirudinea); Nybelinia
      surmenicola, Scolex pleuronectis, and Neobothriocephalus adspinosus (Cestoda);
      Floridosentis sp. and Corynosoma australe (Acanthocephala); Anisakidae
      (Nematoda); and an unidentified hemiurid (Digenea). Univariate analyses showed
      that C. australe has its highest prevalence and mean intensity of infection in
      hosts from shallow waters. Floridosentis sp. showed significant differences along
      the depth gradient, with higher mean intensity and prevalence of infection in
      fish from midwater. Among the ectoparasites, only N. chilensis exhibited
      differences in mean intensity with depth, where intensity of infection increased
      with depth of host habitat. A canonical multivariate analysis demonstrated that
      parasite burdens can be a good predictor of the environment (shallow, mid-, or
      deep water) occupied by the flounders.

PMID- 15715232
TI  - Abomasal parasites in wild sympatric cervids, red deer, Cervus elaphus and fallow
      deer, Dama dama, from three localities across central and western Spain:
      relationship to host density and park management.
AB  - A survey of abomasal parasites in cervids from Central Spain was conducted at 3
      sites, Quintos de Mora (Toledo), Maluenez de Arriba (Caceres), and La Herguijuela
      (Caceres). Commonly occurring helminths belonged to 3 polymorphic species of the
      Ostertagiinae: Spiculopteragia asymmetricalS. quadrispiculata, Ostertagia
      leptospicularis/O. kolchida, and O. drozdzi/O. ryjikovi. Trichostrongylus axei
      was found in very few cases. Ostertagia drozdzi/O. ryjikovi and the minor male
      morphotype, S. quadrispiculata, are reported for the first time in red deer from
      Spain. The 3 ostertagiine species are also reported for the first time in fallow
      deer from Spain. These 3 species of Ostertagiinae are primarily parasites of
      cervids, and nematode species characteristic of domestic ruminants were not
      present. Prevalence of infection by gastrointestinal parasites in cervids was
      high, ranging from 97.5 to 100%, across the 3 areas sampled. Mean intensity of
      infection and abundance showed a positive relationship to the population density
      of red deer. Helminth burdens were higher in fallow deer than in the sympatric
      red deer and may reflect the gregarious social structure and different foraging
      patterns of fallow deer.

PMID- 15715233
TI  - Comparative life histories of two diplostomid trematodes, Ornithodiplostomum
      ptychocheilus and Posthodiplostomum minimum.
AB  - A lack of comparative studies limits our understanding of interspecific variation
      in parasite life histories, especially for species that incorporate asexual and
      resting stages into their life cycles. Ornithodiplostomum ptychocheilus and
      Posthodiplostomum minimum are sympatric diplostomid trematodes that share the
      same first (pond snail, Physa gyrina) and second (fathead minnow, Pimephales
      promelas) intermediate hosts within lakes in Alberta, Canada. Interspecific
      differences in the body sizes of adults, cercariae, and metacercariae were
      evaluated from parasites recovered from laboratory-raised chickens, snails, and
      minnows, respectively. Differences in adult worm fecundity and cercariae
      production were estimated from chickens and snails exposed to known numbers of
      parasite larvae. Posthodiplostomum minimum adults, metacercariae, and eggs were
      97, 86, and 5% larger than those of 0. ptychocheilus, respectively. The average
      numbers of eggs produced per day by P. minimum was 3 times higher than for O.
      ptychocheilus, and P. minimum produced approximately twice as many cercariae per
      day. Although the larger of the 2 species had higher egg and cercariae
      production, conclusions regarding covariation between adult worm size and the
      reproductive rates of other life cycle stages require further studies on related
      species.

PMID- 15715234
TI  - Long-term occurrence of Hemolivia cf. mauritanica (Apicomplexa: Adeleina:
      Haemogregarinidae) in captive Testudo marginata (Reptilia: Testudinidae):
      evidence for cyclic merogony?
AB  - Blood smears from wild-caught, long-term captive tortoises, Testudo marginata,
      revealed the presence of gametocytes of a Hemolivia mauritanica-like
      hemogregarine in the erythrocytes of 72% tortoises examined. Significant
      parasitemia was also found in animals living several years in captivity.
      Experimentally infected tortoises showed no evidence of a decrease in parasitemia
      level more than 15 mo after infection. Morphologically, stages found in
      tortoises' erythrocytes were indistinguishable from those referred to by previous
      workers as H. mauritanica from Testudo graeca. Moreover, successful experimental
      transmission to Hyalomma aegyptium confirms the conspecificity with H.
      mauritanica. The occurrence of H. mauritanica gametocytes in tortoise living up
      to 8 yr in captivity is suggested to result from continuous, long-lasting cyclic
      merogony in tortoises' parenchymatous organs, which is an unknown phenomenon in
      the life cycle of Hemolivia spp.

PMID- 15715235
TI  - Transplacental transmission and abortion in cows administered Neospora caninum
      oocysts.
AB  - Neospora caninum infection is a common cause of bovine abortion. One method by
      which cattle can acquire infection is through ingestion of oocysts; however, this
      has not yet been proved to cause transplacental infection or abortion. In this
      study, 19 cows, pregnant between 70 and 176 days, were administered 1500 to
      115,000 oocysts through an esophageal tube. Seventeen of the cows became
      seropositive, indicating acquisition of infection, whereas 8 negative control
      cows remained seronegative (P < 0.001). Offspring were examined using serology,
      histology, immunohistochemistry, parasite isolation, and polymerase chain
      reaction (PCR). Six offspring were infected and 1 of them was aborted. The
      aborted fetus had typical lesions and positive immunohistochemistry and PCR for
      N. caninum. All 6 cows with infected offspring had continuously rising antibody
      titers, whereas 10 of 11 infected cows with uninfected offspring had falling
      titers after an early apex. The risk of transplacental transmission was increased
      by later exposure times during gestation and by the dose of oocysts (P < 0.01 for
      the 2 combined variables). The lowest dose of oocysts, when administered after
      the 160th day of gestation, caused transplacental infection in 1 of 2 animals.
      This study demonstrates that infection with N. caninum oocysts can cause
      transplacental transmission and abortion in cattle.

PMID- 15715236
TI  - Encapsulation of Myxobolus pendula (Myxosporidia) by epithelioid cells of its
      cyprinid host Semotilus atromaculatus.
AB  - Spores of Myxobolus pendula develop within the cores of complex cysts on the gill
      arch of creek chub Semotilus atromaculatus. Adjacent to, and surrounding, the
      spores are concentric layers of stratified interdigitating cells, whose nature
      was examined by transmission electron microscopy and by immunohistochemical and
      molecular biological techniques. In situ hybridization data using parasite
      derived ribosomal DNA as a probe indicate that infection leads to the
      encapsulation of developing plasmodia by host immune cells that form an
      epithelioid granuloma. Epithelioid cell-cell adhesion is effected by desmosomes
      anchored intracellularly to cytokeratin intermediate filaments. High levels of
      alkaline phosphatase activity are associated with regions of cellular
      interdigitation. The granuloma may serve to limit the spread of the parasite to
      surrounding tissues but does not appear to inhibit diffusion of oxygen and
      nutrients to the developing spores.

PMID- 15715238
TI  - New genus with two new species of capsalid monogeneans from dasyatids in the Gulf
      of California.
AB  - We propose Listrocephalos n. gen. (Monogenea: Capsalidae: Entobdellinae) for 2
      new capsalid species that infect the skin of 2 species of diamond stingrays
      (Dasyatidae) in the Gulf of California. We also provide additional observations
      on 2 previously described capsalid species, which infect the external body
      surface of stingrays and are currently in Entobdella Blainville in Lamarck, 1818,
      and transfer them to the proposed new genus. The members of this genus,
      Listrocephalos corona (Hargis, 1955) n. comb. (type species), Listrocephalos
      guberleti (Caballero and Bravo-Hollis, 1962) n. comb., Listrocephalos kearni n.
      sp., and Listrocephalos whittingtoni n. sp., differ from other entobdellines by
      the combination of having an anterolateral adhesive pad comprising 2 ventral
      columns of raised ovoid structures, I pair of glands that flank the preoral
      depression, a discoid and aseptate haptor that lacks a marginal valve but has
      clover-shaped papillae dispersed radially over its entire ventral surface, minute
      and nonoverlapping median haptoral sclerites, a bizarre chamber yielding a duct
      that opens on the surface of the penis, separate genital pores, and a gland of
      Goto located between the testes and ovary. Listrocephalos kearni n. sp. infects
      Dasyatis brevis and is most easily distinguished from its congeners by the
      combination of lacking penis tubules and having a convoluted proximal portion of
      the vas deferens that occupies the space between the ootype and ovary.
      Listrocephalos whittingtoni n. sp. infects Dasyatis longa and is most easily
      distinguished from its congeners by the combination of having penis tubules and a
      vaginal pore that is located posterior to the level of the uterus. We report
      specimens of L. corona from the ventral body surface of Dasyatis say from a new
      locality, Mississippi Sound, as well as specimens of L. guberleti from the skin
      of 2 new hosts, Urobatis maculatus and Urobatis concentricus, and a new locality,
      Elkhorn Slough, California. We provide a diagnostic key and a table of records
      for Listrocephalos spp.

PMID- 15715237
TI  - An equine protozoal myeloencephalitis challenge model testing a second transport
      after inoculation with Sarcocystis neurona sporocysts.
AB  - Previous challenge studies performed at Ohio State University involved a
      transport-stress model where the study animals were dosed with Sarcocystis
      neurona sporocysts on the day of arrival. This study was to test a second
      transportation of horses after oral inoculation with S. neurona sporocysts.
      Horses were assigned randomly to groups: group 1, transported 4 days after
      inoculation (DAI); group 2, at 11 DAI; group 3, at 18 DAI; and group 4, horses
      were not transported a second time (controls). An overall neurologic score was
      determined on the basis of a standard numbering system used by veterinarians. All
      scores are out of 5, which is the most severely affected animal. The mean score
      for the group 1 horses was 2.42; group 2 horses was 2.5; group 3 horses was 2.75;
      and group 4 horses was 3.25. Because the group 4 horses did not have a second
      transport, they were compared with all other groups. Statistically different
      scores were present between group 4 and groups 1 and 2. There was no difference
      in the time of seroconversion between groups. There was a difference between the
      time of onset of first clinical signs between groups 1 and 4. This difference was
      likely because of the different examination days. Differences in housing and
      handling were likely the reason for the differences in severity of clinical
      signs. This model results in consistent, significant clinical signs in all horses
      at approximately the same time period after inoculation but was most severe in
      horses that did not experience a second transport.

PMID- 15715239
TI  - A new species of Spinicauda (Nematoda: Heterakidae) and other endoparasites in
      Platymantis pelewensis (Anura: Ranidae) from the Palau Islands, Republic of
      Belau, Oceanica.
AB  - Spinicauda fisheri n. sp. from the intestine of Platymantis pelewensis collected
      in the Palau Islands, Republic of Belau, is described and illustrated. Spinicauda
      fisheri represents the 12th species assigned to the genus and the first from
      Oceanica. It is most similar to Spinicauda spinicauda in that the tail ends in a
      filament, but it has 19 pairs of caudal papillae as compared with 5 pairs in S.
      spinicauda. In addition to S. fisheri, 2 species of Cestoda, cysticercoids of
      Joyeuxiella sp. and tetrathyridia of Mesocestoides sp., 2 species of Nematoda,
      Oswaldocruzia bakeri and Physocephalus sp. (larvae in cysts), 1 species of
      Acanthocephala, Acanthocephalus bufonis, and 1 species of Pentastomida, nymphs of
      Kiricephalus pattoni were identified.

PMID- 15715240
TI  - A new species of Sphaeromyxa (Myxosporea: Sphaeromyxina: Sphaeromyxidae) in devil
      firefish, Pterois miles (Scorpaenidae), from the northern Red Sea: morphology,
      ultrastructure, and phylogeny.
AB  - Sphaeromyxa zaharoni n. sp. (Myxosporea) is described from the gallbladder of
      devil firefish, Pterois miles (Scorpaenidae), from coral reefs of the Gulf of
      Eilat, Israel, northern Red Sea. The parasite was found also in bearded
      scorpionfish, Scorpaenopsis barbata, from the same area. This is the first report
      on Sphaeromyxa sp. from this zoogeographical region. The plasmodia are amoeboid
      when young, becoming disc-shaped and elongated when mature. In paraffin sections,
      the plasmodium periphery appears as a finely granulated, strongly eosinophilic
      layer with an intricate surface membrane network. Sphaeromyxa zaharoni n. sp. is
      polysporous, disporoblastic, and has asynchronous sporogenesis. The mature spore
      is elongated and fusiform, has delicately ridged valves, and contains a single,
      binucleated sporoplasm. In valvular view, the tips are truncated. The mean spore
      size is length 14.5 microm, width 4.8 microm, and polar capsule 4.8 x 3.4 microm.
      The 2 equally sized ovoid polar capsules are positioned at opposite ends of the
      spore, each containing a filament loosely folded in 2 loops. The fine structure
      of the sporoblast and spore corresponded with previously studied Sphaeromyxa
      species. According to small-subunit ribosomal DNA gene sequence analysis, S.
      zaharoni n. sp. is most closely related to 2 Myxidium spp. The close phylogenetic
      relatedness of Sphaeromyxa and Myxidium and similar spore morphology raises the
      question whether these 2 genera should be maintained in separate families and
      suborders.

PMID- 15715241
TI  - Two new nematode species, Orientatractis campechensis n. sp. and Orientatractis
      chiapasensis n. sp. (Nematoda: Atractidae) from cichlid fishes in southern Mexico
      and Nicaragua.
AB  - Two new nematode species, Orientatractis campechensis n. sp. and Orientatractis
      chiapasensis n. sp. (Atractidae, Cosmocercoidea), are described from the
      intestine of cichlid fishes collected in localities of southeastern Mexico and
      Nicaragua. These atractid nematodes are characterized by the presence of a
      cephalic end armed with 4 marked, Y-shaped, well-sclerotized pieces, consisting
      of 2 "horns" extending outward and downward and immediately below a single-horned
      structure. Both new species differ from the other 2 species of Orientatractis
      (Orientatractis leiperi and Orientatractis levanhoai) mainly in the body
      measurements, presence of a vulvar appendix, lengths of spicules and of the
      gubernaculum, distribution of caudal papillae, and the number of anterior
      sclerotized structures. Morphological and biometrical variations were evident
      among specimens from different hosts and localities, with the larger organisms
      being collected from Vieja bifasciata and Cichlasoma pearsei. Orientatractis
      campechensis and O. chiapasensis represent the first 2 species of this genus
      parasitizing freshwater fishes; the other species have been found in amphibians
      and reptiles.

PMID- 15715242
TI  - Revision of the genus Stictospora and description of Stictospora villani, n. sp.
      (Apicomplexa: Eugregarinida: Actinocephalidae) from larvae of the Japanese
      beetle, Popillia japonica (Coleoptera: Scarabaeidae), in Michigan.
AB  - Stictospora villani n. sp. is described from larvae of the Japanese beetle
      Popillia japonica (Coleoptera: Scarabaeidae) from southern Michigan. Stictospora
      villani is distinguished from known species of the genus by differences in gamont
      size and by structural details of the epimerite. In general, S. villani is
      smaller than other known species of the genus and possesses an epimerite with a
      margin of 20-24 sympetalous, pendulate, narrowly to very narrowly elliptoid
      lamina. Previously described species are characterized by epimerites with notably
      fewer marginal lamina. A heretofore unrecognized protistan is diagnosed from the
      coelomic fat bodies and tentatively placed within the Neogregarinorida. We
      conclude that previous workers have mistaken this neogregarine for the gametocyst
      and oocyst of Stictospora, which are described in this study for the first time.
      The generic diagnosis of Stictospora is revised to encompass the epimeritic
      variation of its constituent species and to correctly reflect the morphology of
      the oocyst.

PMID- 15715243
TI  - Lanceimermis palustris n. sp. and Telomermis palustris n. sp. (Nematoda:
      Mermithidae) parasites of chironomid (Insecta: Diptera) adults from Lake Alice
      Bog in northern Minnesota.
AB  - In the summer of 2003, chironomid imagoes eclosing from Lake Alice Bog in
      Minnesota yielded mermithid nematodes of 2 new species. Lanceimermis palustris n.
      sp. is distinguished from the other 14 species of the genus by the subventral
      mouth position, thinness of the hook-shaped spicule, body index, and structure of
      the male tail muscles. Telomermis palustris n. sp. is distinguished from the only
      other species of the genus by the structure of the amphids, body length, maximum
      body width, length of the esophagus, and the presence of a minute larval terminal
      horn. Lanceimermis palustris n. sp. hosts were Chironomus maturus Johannsen and
      T. palustris n. sp. hosts were Tanytarsus mendax Kieffer, Paratanytarsus nr.
      dissimilis n. sp., and Micropsectra polita (Malloch). In both mermithid species,
      the percent of mermithid males per host increased with the intensity of the
      infection.

PMID- 15715244
TI  - Redescription of Camallanus hypophthalmichthys Dogel and Akhmerov, 1959
      (Nematoda: Camallanidae) and its first record from fishes in China.
AB  - The nematode Camallanus hypophthalmichthys Dogel and Akhmerov, 1959 is
      redescribed from specimens collected from the intestine of the bighead carp
      Aristichthys nobilis, from Liangzihu Lake (Yangtze River basin), Hubei Province,
      central China. The light and scanning electron microscopical examination made it
      possible to study in detail the morphology of this so far little-known species
      and to confirm its validity. The main specific features of C. hypophthalmichthys
      distinguishing it from the most similar Camallanus spp. is the presence of 3
      small caudal processes on the male tail tip, 13-16 longitudinal ridges on the
      inner surface of the valve of the buccal capsule, and the arrangement of preanal
      and postanal genital papillae in the male. This finding represents a new host
      record, the first record of this parasite in the Yangtze River basin, and the
      first documented record of C. hypophthalmichthys from China. Camallanus
      hypophthalmichthys is considered a specific intestinal parasite of fishes of the
      cyprinid Hypophthalmichthyinae.

PMID- 15715245
TI  - Hematozoa of the avian family Brachypteraciidae (the ground-rollers).
AB  - The Brachypteraciidae is an avian family endemic to Madagascar. Members of this
      family were mist-netted in Madagascar, and blood smears were made to screen for
      the presence of hematozoa. Smears were stained with Giemsa and examined at x100,
      x160, and x1000 for hematozoa. Three new species of avian hematozoa from wild
      caught ground-rollers in Madagascar are described. Haemoproteus goodmani n. sp.
      is found in the pitta-like ground-roller (Atelornis pittoides), whereas
      Haemoproteus forresteri n. sp. and Leucocytozoon frascai n. sp. are from the
      rufous-headed ground-roller (Atelornis crossleyi). These represent the first
      hematozoa described from this family.

PMID- 15715246
TI  - Hematozoa of the avian family Philepittidae (the asities and sunbird asities).
AB  - Blood smears from birds in the Philepittidae, endemic to Madagascar, were
      examined for the presence of hematozoa. All slides were read on a compound
      microscope at x100, x160, and x1000. To date, no species of avian hematozoa has
      been reported from asities in Madagascar, although parasites have been observed.
      Leucocytozoon greineri n. sp. is described from the common sunbird asity
      (Neodrepanis coruscans) and is also reported from the velvet asity (Philepitta
      castanea). It is a relatively small species of Leucocytozoon, less than 2 times
      the size of uninfected erythrocytes. The parasite is capped by the host cell
      nucleus, covering 38% of the parasite perimeter. This represents the first
      description of hematozoa from this family.

PMID- 15715247
TI  - Hematozoa of the avian family Vangidae (the vangas).
AB  - To date, limited surveys have been conducted on the endemic avifauna of
      Madagascar with regard to hematozoa. Wild-caught birds from the Vangidae, endemic
      to Madagascar and the Comoros Islands, were mist-netted, and blood smears were
      made. Slides were examined for the presence of hematozoa at x100, x160, and x1000
      using a light microscope. Parasites were measured using established techniques,
      and morphometrics were compared. On the basis of their distinctive morphologies
      and morphometrics, 4 new species of avian hematozoa are described in this study.
      Haemoproteus vangii n. sp. and Leucocytozoon lairdi n. sp. occur in the blue
      vanga (Cyanolanius madagascarinus), whereas Haemoproteus madagascariensis n. sp.
      and Leucocytozoon bennetti n. sp. are described from the hook-billed vanga (Vanga
      curvirostris). These represent the first hematozoa described from this family.

PMID- 15715248
TI  - Amoebacidal effects of serum from the American alligator (Alligator
      mississippiensis).
AB  - Treatment of axenic Naegleria gruberi cultures with alligator serum resulted in
      time-dependent amoebacidal activity, with measurable activity at 5 min and
      maximal activity occurring at 20 min. The amoebacidal activity was concentration
      dependent, with measurable activity at 25% serum, whereas treatment of amoebas
      with undiluted serum resulted in only 16% survival. The efficacy was dependent on
      the concentration of amoebas, with higher survival rates at high amoeba densities
      and lower survival rates at low amoeba densities. The amoeba-killing effects of
      alligator serum were broad in spectrum because the serum was effective against 3
      strains of Naegleria species tested and 4 Acanthamoeba species, which have been
      reported to be resistant to human serum complement-mediated lysis. The
      amoebacidal effects of alligator serum were temperature dependent, with optimal
      activity at 15-30 C and a decrease in activity below 15 C and above 30 C. The
      amoebacidal activity of alligator serum was heat labile and protease sensitive,
      indicating the proteinaceous nature of the activity, and was also inhibited by
      ethylenediaminetetraacetic acid, which indicated a requirement for divalent metal
      ions. These characteristics strongly suggest that the amoebacidal properties of
      alligator serum are because of complement activity.

PMID- 15715249
TI  - Diagnostic value of rK39 dipstick in zoonotic visceral leishmaniasis in Turkey.
AB  - K39 is a repetitive immunodominant epitope in a kinesin-related protein expressed
      predominantly in the amastigotes of visceral Leishmania spp. Enzyme immunoassays
      of patient's sera with recombinant K39 (rK39) proved to be highly specific and
      sensitive for diagnosis of active visceral leishmaniasis (VL, kala-azar). The
      same assays in dipstick format were also found effective for diagnosis of both
      human VL (HVL) and canine VL (CanVL) in most endemic areas of these diseases.
      Fifty-eight human patients and 22 dogs, clinically suspected of kala-azar, were
      screened with rK39 dipstick in comparison with the conventional methods of
      diagnosis, i.e., microscopic examinations of bone marrow and lymph node aspirates
      and immunofluorescent antibody tests (IFAT), respectively. Sixteen patients and
      12 dogs were found to be rK39 dipstick positive. The results were corroborated
      with those of parasitological examinations, except 1, rK39-positive but smear
      negative, case in each group. IFAT of the 2 discordant cases gave positive
      results. The rK39 dipstick is thus reliable for diagnosis of both HVL and canVL
      cases in Turkey.

PMID- 15715250
TI  - Experimental infection of ponies with Sarcocystis fayeri and differentiation from
      Sarcocystis neurona infections in horses.
AB  - Sarcocystis neurona and Sarcocystis fayeri infections are common in horses in the
      Americas. Their antemortem diagnosis is important because the former causes a
      neurological disorder in horses, whereas the latter is considered nonpathogenic.
      There is a concern that equine antibodies to S. fayeri might react with S.
      neurona antigens in diagnostic tests. In this study, 4 ponies without
      demonstrable serum antibodies to S. neurona by Western immunoblot were used.
      Three ponies were fed 1 x 10(5) to 1 x 10(7) sporocysts of S. fayeri obtained
      from dogs that were fed naturally infected horse muscles. All ponies remained
      asymptomatic until the termination of the experiment, day 79 postinoculation
      (PI). All serum samples collected were negative for antibodies to S. neurona
      using the Western blot at the initial screening, just before inoculation with S.
      fayeri (day 2) and weekly until day 79 PI. Cerebrospinal fluid samples from each
      pony were negative for S. neurona antibodies. Using the S. neurona agglutination
      test, antibodies to S. neurona were not detected in 1:25 dilution of sera from
      any samples, except that from pony no. 4 on day 28; this pony had received 1 X
      10(7) sporocysts. Using indirect immunofluorescence antibody tests (IFATs), 7
      serum samples were found to be positive for S. neurona antibodies from 1:25 to
      1:400 dilutions. Sarcocystis fayeri sarcocysts were found in striated muscles of
      all inoculated ponies, with heaviest infections in the tongue. All sarcocysts
      examined histologically appeared to contain only microcytes. Ultrastructurally,
      S. fayeri sarcocysts could be differentiated from S. neurona sarcocysts by the
      microtubules (mt) in villar protrusions on sarcocyst walls; in S. fayeri the mt
      extended from the villar tips to the pellicle of zoites, whereas in S. neurona
      the mt were restricted to the middle of the cyst wall. Results indicate that
      horses with S. fayeri infections may be misdiagnosed as being S. neurona infected
      using IFAT, and further research is needed on the serologic diagnosis of S.
      neurona infections.

PMID- 15715251
TI  - C13 norisoprenoids from Brassica fruticulosa.
AB  - Five C13 norisoprenoids, one of them glucosilated, have been isolated from the
      leaves of Brassica fruticulosa (Brassicaceae). The structure (3S,4R,7E,9S)-3,4,9
      trihydroxy-5,7-megastigmadiene, has been assigned to the new compound. All the
      structures have been determined by spectroscopic means and chemical correlations.

PMID- 15715252
TI  - Highlights in oleuropein aglycone structure.
AB  - Oleuropein hydrolysis products, obtained both by endogenous beta-glucosidase and
      almond commercial one, were investigated by classic methodologies and by 1HNMR
      experiments. We found that both presence and relative amount of the different
      compounds in the reaction mixture are stricly related to the used enzyme.

PMID- 15715253
TI  - Biotransformation of alpha-bulnesene using a plant pathogenic fungus, Glomerella
      cingulata as a biocatalyst.
AB  - The biotransformation of a sesquiterpene having a guaiane skeleton, namely (+)
      alpha-bulnesene was investigated using the plant pathogenic fungus, Glomerella
      cingulata as a biocatalyst. (+)-alpha-Bulnesene was oxidized at the double bond
      of the isopropenyl group and hydroxylated at the allylic methyl group to
      (4S,5S,7R)-1(10)-guaien-11,13,15-triol.

PMID- 15715254
TI  - Phenolic constituents from Ephedra nebrodensis.
AB  - Two new phenolic glycosides, 4-hydroxy-3-(3-methyl-2-butenyl)phenyl beta-D
      glucopyranoside (nebrodenside A) and O-coumaric acid beta-D-allopyranoside
      (nebrodenside B), were isolated from the aerial parts of Ephedra nebrodensis. In
      addition, O-coumaric acid glucoside, (-)-epicatechin, and (-)-ephedrine were also
      isolated. The structures were deduced from extensive 1D and 2DNMR spectroscopy
      (1H, 13C, DQF-COSY, TOCSY, GHSQC, GHMQC, ROESY) as well as mass spectrometry (EI
      and HR-MALDI). (-)-Epicatechin showed weak antiviral activity against Influenza A
      virus and very weak cytotoxicity against MDCK cells.

PMID- 15715255
TI  - A new pinoresinol-type lignan from Ligularia kanaitizensis.
AB  - A new pinoresinol-type Lignan, 9alpha-angloyloxypinoresinol (1), was isolated
      from the roots and rhizomes of Ligularia kanaitizensis (Franch.) Hand.-Mazz, in
      addition to a known compound, 9alpha-hydroxypinoresinol (2). The structure of
      this new lignan (1) was established on the basis of 1D and 2D NMR experiments.
      Anti-HIV-1 RT biological assay showed that 1 was inhibitory to HIV-1 RT.

PMID- 15715256
TI  - Chemical constituents of Bacopa procumbens.
AB  - Phytochemical investigation of Bacopa procumbens afforded two new phenolic
      glycosides 1 and 2, for the first time, along with 12 known compounds 3-14.
      Structures of these compounds were established based on spectral and chemical
      evidences.

PMID- 15715257
TI  - Isolation and structure elucidation of diazaquinomycin C from a terrestrial
      Streptomyces sp. and confirmation of the akashin structure.
AB  - In the screening of terrestrial Streptomycetes for bioactive components, a new
      antibiotic designated as diazaquinomycin C (2b) was isolated. The new antibiotic
      was found to be a homologue of diazaquinomycin A (2a) by spectroscopic methods
      and by comparison of the NMR data with those of 2a. The same strain additionally
      produced the akashins 1a-1c. The configuration of the N-O acetale bond in these
      rare glycosylated dichloroindigo derivatives was confirmed to be beta.

PMID- 15715258
TI  - Insecticidal amides from fruits of Piper nigrum Linn.
AB  - The petroleum ether and ethyl acetate fractions of dried ground seeds of Piper
      nigrum Linn. afforded sixteen compounds (1-16) including one new insecticidal
      amide, pipwaqarine (1) and six constituents (3,4,6,7,11,15) previously unreported
      from this plant. The structure of (1) has been elucidated through extensive 1D-,
      2D-NMR spectral studies as, 1-[13-(3',4'-methylenedioxyphenyl)-2E,4E,12E
      tridecatrienoyl]-N-isopentylamide, while those of known constituents through
      comparison of spectral data. 1 exhibited toxicity of 30ppm against fourth instar
      larvae of Aedes aegypti Liston determined by WHO method. A portion of petroleum
      ether fraction was also subjected to GC and GC-MS analysis resulting in the
      identification of three compounds (17-19) using the NIST Mass spectral search
      program 1998 and Kovat's retention indices. Two of these compounds, 17 and 18,
      are reported for the first time from this plant.

PMID- 15715259
TI  - Cymosanine, a novel C19-quassinoid from Simaba subcymosa.
AB  - Cymosanine (1) and three further known quassinoids, cedronin (2), chaparrinone
      (3), and simarolide (4), were isolated from the root bark of Simaba subcymosa.
      The structures were established by spectroscopic data, mainly 1D, 2D NMR and mass
      spectra.

PMID- 15715260
TI  - Phenolic profile of hazelnut (Corylus avellana L.) leaves cultivars grown in
      Portugal.
AB  - In this study, phenolic compounds of hazelnut leaves of 10 different cultivars
      with the same cultural, geographical, geological and climatic conditions were
      analyzed by HPLC/DAD and HPLC/DAD/MS/MS - ESI. Eight phenolic compounds (3
      caffeoylquinic acid, 5-caffeoylquinic acid, caffeoyltartaric acid, p
      coumaroyltartaric acid, myricetin 3-rhamnoside, quercetin 3-glycoside, quercetin
      3-rhamnoside and kaempferol 3-rhamnoside) were identified and quantified. All of
      the analyzed samples showed a similar phenolic profile, in which myricetin 3
      rhamnoside and quercetin 3-rhamnoside were the major compounds and
      caffeoyltartaric and p-coumaroyltartaric acids were present in vestigial amounts.

PMID- 15715261
TI  - A novel bis-furan derivative, two new natural furan derivatives from Rehmannia
      glutinosa and their bioactivity.
AB  - A novel bis-furan derivative and two new natural furan derivatives were isolated
      from the CHCl3 extracts of the dried roots of Rehmannia glutinosa (Gaerth)
      Lilosch. Their structures were identified as 1,5-bis(5-methoxymethyl)furan-2-yl
      penta-1,4-dien-3-one 1, (E)-4-(5-(methoxymethyl)furan-2-yl)but-3-en-2-one 2 and
      (E)-4-(5-(hydroxymethyl)furan-2-yl)but-3-en-2-one 3 on the basis of spectral
      data. Moreover, biological assay showed that 1 (10 microg/mL) and 3 (10
      microg/mL) can promote immune activity, 2 (100 microg/mL) and 3 (100 microg/mL)
      inhibit immune activity and 1 can inhibit blood platelet aggregation.

PMID- 15715262
TI  - Xanthones from calli of Hypericum perforatum subsp. perforatum.
AB  - Two new xanthone derivatives, 1-hydroxy-5,6,7-trimethoxyxanthone and 3-O
      methylpaxanthone were isolated from callus of Hypericum perforatum subsp.
      perforatum together with the known paxanthone, cadensin G, 1-hydroxy-6,7
      dimethoxyxanthone, 1,3,6,7-tetrahydroxyxanthone, and 1,3,5,6
      tetrahydroxyxanthone. The structures of the new compounds were established by
      spectroscopic methods.

PMID- 15715263
TI  - Phenolics with antiviral activity from Millettia erythrocalyx and Artocarpus
      lakoocha.
AB  - From the leaves of Millettia erythrocalyx, a new flavone named 3',5'-dimethoxy
      [2",3": 7,8]-furanoflavone and three known compounds were isolated. Assays for
      anti-herpes simplex virus activity (HSV-1 and HSV-2) were performed on 24
      phenolic compounds obtained from M. erythrocalyx and Artocarpus lakoocha. It was
      found that the flavones ovalifolin, pongol methyl ether and millettocalyxin A,
      and the stilbene oxyresveratrol possessed moderate activity against both types of
      HSV. In addition, oxyresveratrol was evaluated for potential anti-HIV activity
      against a wild-type human immunodeficiency virus type 1 (HIV-1/LAI) isolate and
      was found to be a modest inhibitor of HIV (EC50 28.2 microM), showing no toxicity
      in PBM, CEM and Vero cells at 100 microM. The heartwood of A. lakoocha, which
      contains a large amount of oxyresveratrol, could be considered as a source of
      starting material for the development of new natural product-based anti-HSV and
      anti-HIV agents.

PMID- 15715264
TI  - Natural product propolis: chemical composition.
AB  - The chemical composition of propolis from East Mediterranean (Hatay, Adana and
      Mersin) was studied in order to determine the major compounds by using GC-MS. In
      this study, the ethanolic extract of propolis prepared by mixing 1900mL 70%
      ethanol and 100g propolis was used. Chemical analysis of propolis extracts
      indicated that the propolis samples had high concentrations of the aromatic
      acids, esters and other derivatives which are responsible for the anti-bacterial,
      anti-fungal, anti-viral, anti-inflammatory and anti-cancer properties of propolis
      such as benzyl cinnamate, methyl cinnamate, caffeic acid, cinnamyl cinnamate and
      cinnamoylglcine besides the most common compounds as fatty acid, terpenoids,
      esters, alcohols hydrocarbons and aromatic acids.

PMID- 15715265
TI  - Analysis and quantification of flavonoidic compounds from Portuguese olive (Olea
      europaea L.) leaf cultivars.
AB  - Twenty three samples of 18 Portuguese olive leaf cultivars were analysed by a
      reversed-phase HPLC/DAD procedure and eight flavonoidic compounds were identified
      and quantified (luteolin 7,4'-O-diglucoside, luteolin 7-O-glucoside, rutin,
      apigenin 7-O-rutinoside, luteolin 4'-O-glucoside, luteolin, apigenin and
      diosmetin). Luteolin 7,4'-O-diglucoside and luteolin 4'-O-glucoside were
      identified by HPLC/DAD/MS/MS - ESI. The studied olive leaf samples showed a
      common phenolic pattern, in which luteolin 4'-O-glucoside was almost always the
      major compound.

PMID- 15715266
TI  - Antimicrobial triterpenes from Poulsenia armata Miq. Standl.
AB  - Crude petroleum ether extract from the bark of Poulsenia armata showed
      antimicrobial activity. Activity-guided fractionation led to the isolation and
      structure elucidation of two active new triterpene derivatives, the stearate of
      glut-5-en-3beta-ol (1) and 3beta,28-diacetoxyurs-12-ene (4), for the first time
      as naturally occurring compounds. Compound 4 has previously been synthesized. The
      structures were determined by 1D- and 2D-NMR spectroscopy, mass spectrometry and
      chemical transformations. This is the first report on the chemistry and
      pharmacology of the genus.

PMID- 15715267
TI  - Arsenic species in solutions for parenteral nutrition.
AB  - BACKGROUND: In spite of its high toxicity, arsenic is a common contaminant in
      pharmaceuticals. This is stated by pharmacopoeias' monographs where it is not
      generically included with other heavy metals, but has its own specifications.
      Arsenic should not exceed 0.1 mg/L in most pharmaceutical products for IV
      administration. This limit, however, was established without taking into
      consideration the specific arsenic species which contribute to this amount. In
      this work, the presence of arsenite and arsenate species in solutions of amino
      acids, salts, vitamins, and lipids commercialized for IV administration was
      investigated. METHODS: The measurements were done by hydride generation atomic
      absorption spectrometry. RESULTS: The results showed that all commercial
      formulations contain both arsenic species in some level; however, the total
      arsenic content exceeded the allowed limit in only a few samples. Calcium
      gluconate, sodium bicarbonate, heparin, and vitamin solutions were the most
      contaminated, presenting total arsenic concentration ranging from 62 to 249
      microg/L. The most important finding, however, was the different ratios
      As(V)/As(III) among the formulations. Whereas practically only As(V) was found in
      ampoules containing water for injection and salt solutions (NaCl, KC1,
      phosphates), As(III) predominated in solutions of vitamins, gluconate, and
      glucose. As these are reducing substances, we investigated the possibility of
      their reaction with As(V) and its conversion into As(III). The heating of As(V)
      in the presence of gluconate, glucose, ascorbic acid, methionine, isoleucine,
      sodium chloride, and pure water, in autoclave for 15 minutes, showed that,
      whereas no As(III) was found in pure water and sodium chloride solution,
      approximately 50% of As(V) was converted into As(III) in the remainder of the
      solutions. CONCLUSIONS: The results showed that As(V), the main species in these
      formulations, may be converted into As(III), depending on the presence of
      reducing substances among the formulation constituents.

PMID- 15715268
TI  - Diarrhea in severely burned children.
AB  - BACKGROUND: Diarrhea is a common problem in critically ill patients. Our patients
      are fed a high-carbohydrate enteral formula. We hypothesized that diarrhea in our
      patients may be related to the osmotic effects of unabsorbed carbohydrate in the
      small intestine and colon. METHODS: We studied 19 patients, 3 months to 17 years,
      with burns >40% total body surface area. Each subject was studied weekly for up
      to 4 weeks postburn. Breath H2 concentration was measured. For the 24-hour period
      before the breath H2 measurement, the enteral carbohydrate intake, stool volume,
      and total enteral fluid volume were recorded. At each of several weekly intervals
      for each subject, the times when stool volume and enteral carbohydrate intake
      were each maximal were noted. RESULTS: Maximal stool volume ranged from 12 to 69
      mL/kg/d. At the time point of maximal carbohydrate intake, diarrhea (stool volume
      >10 mL/kg/d) occurred in 18 of 19 patients, and maximal stool volume occurred in
      10 of 19. Breath H2 concentration (ppm/5% CO2; mean +/- SEM) was 5.5 +/- 3.5 at
      the time of maximal carbohydrate intake, and was 25 +/- 20 at maximal stool
      volume. There were no correlations among breath H2 concentration, stool volume,
      enteral fluid intake, and enteral carbohydrate intake. CONCLUSIONS: Almost all
      the subjects had diarrhea over several weeks postburn. The lack of correlation of
      either carbohydrate intake or breath H2 with stool volume suggests that diarrhea
      in these patients may be caused by factors other than carbohydrate malabsorption.
      These data do not support altering nutrition support because of watery diarrhea.

PMID- 15715269
TI  - Effect of jejunal long-term feeding in chronic pancreatitis.
AB  - BACKGROUND: In the late course of chronic pancreatitis (CP), weight loss is often
      seen because of reduced caloric intake and a reduction of pancreatic enzyme
      secretion, resulting in maldigestion. Most of these patients can be managed by
      dietary recommendations and pancreatic enzyme supplementation. However,
      approximately 5% of these patients are reported to be candidates for enteral
      nutrition support during their course of CP. Although small bowel access for
      enteral feeding can be easily obtained by percutaneous endoscopic
      gastrojejunostomy (PEG/J) or direct percutaneous endoscopic jejunostomy (DPEJ),
      to date there are no data regarding clinical outcome and safety of long-term
      jejunal feeding in CP. METHODS: From January 1999 to October 2002, 57 patients
      receiving enteral nutrition by PEG/J or DPEJ were retrospectively analyzed during
      a follow-up period of 6 months. There were 38 females and 19 males, with an
      average age of 46.6 years. RESULTS: Small-bowel access was obtained by PEG/J in
      53 patients and by DPEJ in 4. Duration of enteral feeding was 113 days. Average
      body weight significantly increased from 64.8 kg at day 1 to 69.1 kg at day 180
      (p < .001). The percentage of patients with abdominal pain decreased from 96% to
      23%. One patient sustained a colon mesentery injury after DPEJ tube placement.
      CONCLUSIONS: Long-term nutrition support by PEG/J or DPEJ in patients with
      symptomatic, chronic pancreatitis increases patients' body weight and decreases
      the degree of malnutrition, abdominal pain, and other gastrointestinal symptoms.
      The underlying mechanisms for these observations are unclear and require further
      investigation. Small-bowel rest with reduced pancreatic gland stimulation might
      be a key component. Moderately to severely malnourished patients who do not
      respond to oral dietary interventions and who are candidates for elective
      pancreatic surgery might also be candidates for long-term preoperative jejunal
      feeding to reduce malnutrition-associated perioperative complications. In
      experienced hands, we feel that long-term jejunal feeding is safe, with minimal
      major complications.

PMID- 15715270
TI  - Glycemic and lipid control in hospitalized type 2 diabetic patients: evaluation
      of 2 enteral nutrition formulas (low carbohydrate-high monounsaturated fat vs
      high carbohydrate).
AB  - BACKGROUND: Type 2 diabetic patients may need enteral nutrition support as part
      of their treatment. The objective was to compare glycemic and lipid control in
      hospitalized patients with type 2 diabetes requiring feeding via nasogastric tube
      using enteral feedings with either a highcarbohydrate or a high-monounsaturated
      fat content. METHODS: This trial included type 2 diabetes patients admitted to
      the hospital for neurologic disorders or head and neck cancer surgery who
      received either a low-carbohydrate-high-mono-unsaturated-fat (Glucerna) or a high
      carbohydrate diet (Precitene Diabet). Glycemic and lipid control was determined
      weekly. Safety and gastrointestinal tolerance were also assessed. RESULTS: A
      total of 104 patients were randomized and 63 were evaluable according to
      preestablished protocol criteria. Median duration of therapy was 13 days in both
      groups. Mean glucose was significantly increased at 7 days of treatment (p =
      .006) in the Precitene arm, with no significant variations in the Glucerna arm.
      Mean weekly blood triglycerides levels in the Precitene arm were increased
      without reaching statistical significance, whereas patients in the Glucerna arm
      showed a stable trend. Patients in the Precitene arm showed a significantly
      higher incidence of diarrhea than patients in Glucerna arm (p = .008), whereas
      the incidence of nausea was smaller in the Precitene arm than in the Glucerna arm
      (p = .03). CONCLUSIONS: An enteral formula with lower carbohydrate and higher
      monounsaturated fat (Glucerna) has a neutral effect on glycemic control and lipid
      metabolism in type 2 diabetic patients compared with a high-carbohydrate and a
      lower-fat formula (Precitene Diabet).

PMID- 15715271
TI  - Impaired intestinal cell proliferation and cell death in leptin-deficient obese
      mice.
AB  - BACKGROUND: After massive small-bowel resection and loss of absorptive capacity,
      residual intestine has compensatory ability to adapt by cellular hyperplasia and
      increased absorptive function. Growth factors have been shown to enhance
      intestinal adaptation, but the mechanisms involved are not well defined. Leptin
      has been shown to function as a trophic factor in the intestine and enhances
      carbohydrate absorption after small-bowel resection. Therefore, we hypothesized
      that leptin deficiency may impair the adaptive response by modulating cellular
      proliferation or cell death after small-bowel resection. METHODS: Twelve-week-old
      male lean control (C57BL/6J, n = 28) and leptin-deficient (Lep(ob), n = 24) obese
      mice underwent sham laparotomy, intestinal transection, or 50% proximal small
      bowel resection. Mice were killed at 48 hours postresection, and remnant
      intestine was harvested. Phenotypic analysis to assess adaptation included
      characterization of cell proliferation (percentage BrdU incorporation), apoptosis
      (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend
      labeling assay), and morphometric response (villus height, crypt depth). RESULTS:
      The percentage S-bromodeoxyuridine (BrdU) incorporation and apoptotic indices of
      obese transected mice were significantly lower than lean transected mice (7.3 vs
      21.9% and 0.70 vs 1.53% respectively, p < .05). In resected animals, the
      percentage BrdU incorporation and apoptotic indices of obese resected mice were
      significantly lower than for lean resected (6.1 vs 22.0% and 0.93 vs 1.80%
      respectively, p < .05). No differences between groups, regardless of surgery,
      were identified in villus height or crypt depth. CONCLUSIONS: Therefore, we
      conclude that leptin deficiency impairs both cell proliferation and cell death in
      the early adaptive period after either small-bowel transection or resection.

PMID- 15715272
TI  - The effect of preventive use of alanyl-glutamine on diaphragm muscle function in
      cecal ligation and puncture-induced sepsis model.
AB  - BACKGROUND: Low muscle glutamine levels during sepsis are associated with reduced
      protein synthesis and elevated protein breakdown, in particular myofibrillar
      protein breakdown. Thus, in a cecal ligation and puncture (CLP)-induced sepsis
      model in the rat, we hypothesized that glutamine pretreatment would protect the
      diaphragm muscle function. METHODS: Eighty-four male Wistar rats weighing between
      180 g and 200 g received standard amino acid solution 1.2 g kg(-1) per day
      intraperitoneally (IP) or standard amino acid solution 1.2 g kg(-1) per day plus
      alanyl-glutamine (GLN) 0.25 g kg(-1) per day (IP) during the first 6 days of the
      experiment. On the seventh day, CLP or sham procedures were applied. The sham and
      CLP groups were equally divided into 3 subgroups according to the termination of
      the experiment, which took place at either the 24th hour, 48th hour, or 72nd
      hour. After the compound muscle action potentials (CMAP) were recorded from the
      diaphragms of the rats at these selected times, they were decapitated under
      ketamine/xylazine anesthesia, and diaphragms were harvested for biochemical and
      histopathological examination. RESULTS: The mean area and amplitude of CMAP were
      significantly larger in sham+GLN groups when compared with CLP and CLP+GLN groups
      at all times (p < .05). Diaphragm Ca+2 -ATPase levels were found to be
      significantly decreased in CLP group at all times compared to sham groups (p <
      .05). Diaphragm reduced glutathione levels were significantly higher in sham+GLN
      groups when compared with CLP and CLP+GLN groups at all times (p < .05). In
      histopathologic assessment, moderate neutrophil infiltration, which was observed
      in CLP48, was significantly reduced with alanyl-glutamine supplementation in
      CLP+GLN48 group (p < .05). CONCLUSIONS: This study showed that glutamine
      pretreatment did not improve diaphragm muscle function, but prevented the
      biochemical and histopathological changes in diaphragmatic muscle in CLP-induced
      sepsis. However, further studies are needed to clarify whether a higher dose of
      glutamine supplementation might protect the diaphragmatic muscle functions.

PMID- 15715273
TI  - Enteral feeding preserves gut Th-2 cytokines despite mucosal cellular adhesion
      molecule-1 blockade.
AB  - BACKGROUND: Parenteral nutrition (PN) decreases gut-associated lymphoid tissue
      (GALT), the intestinal IgA stimulating cytokines IL-4 and IL-10 in gut
      homogenates, intestinal IgA levels and the expression of Peyer patch (PP) mucosal
      cellular adhesion molecule-1 (MAdCAM-1), an adhesion molecule found on the high
      endothelial venules of PP and other tissues. IL-4 in PP stimulates MAdCAM
      expression in vitro. MAdCAM-1 blockade with MECA-367 reduces GALT cell
      populations to PN levels but maintains intestinal IgA levels if the animals are
      chow fed. This study compares IL-4 levels in PP of chow and PN fed mice and
      measures the effects of MAdCAM blockade on IL-4 and IL-10 levels in gut
      homogenates of chow fed mice. We hypothesized that in vivo IL-4 levels drop in PP
      of PN fed mice and IL-4 and IL-10 levels are maintained after MAdCAM-1 blockade
      in chow fed mice. METHODS: Exp 1: 18 mice received chow or PN for 5 days to
      determine PP IL-4 levels. Exp 2: 44 mice were randomized to chow + control
      monoclonal antibody (mAb), chow + MECA-367 (anti-MAdCAM-1 mAb) or PN for 4 days
      before measurement of IL-4 and IL-10 levels in gut homogenates. RESULTS: Exp 1:
      IL-4 levels in vivo were lower in PP of PN-fed mice than chow fed mice (92.0 +/-
      15.1 pg/mL vs 251.1 +/- 14.8, p = .0003). Exp 2: IL-4 levels were significantly
      higher in chow + control mAb (187.1 +/- 44.1 pg/mL) and chow + MECA-367 (110.9 +/
      19.1 pg/mL) groups than PN mice (21.8 +/- 30.6 pg/mL, p < .02 vs chow + control
      or chow + MECA-367). IL-10 levels were significantly lower with PN (23.1 +/- 40.9
      pg/mL) with chow+control (174.0 +/- 22.2 pg/mL p < .01), or chow + MECA-367
      (181.7 +/- 23.1 pg/mL, p < .02 vs PN). CONCLUSIONS: PN-feeding reduces in vivo IL
      4 levels in PP (consistent with lowered MAdCAM-1 expression) and IL-4 and IL-10
      levels in gut homogenates compared with chow. Despite MAdCAM-1 blockade, enteral
      feeding preserved gut IL-4 levels and increased IL-10 levels consistent with
      preserved IgA levels.

PMID- 15715274
TI  - The role of Kupffer cells after major liver surgery.
AB  - BACKGROUND: Kupffer cells (KCs) are the resident macrophages of the liver. KCs
      have an enormous endotoxin eliminating capacity. Endotoxins play an important
      role in the development of systemic complications after partial hepatectomy by
      activating KCs. The role of KCs and endotoxins after partial hepatectomy is
      investigated. METHODS: Wistar rats (n = 16, 250-275 g) were randomly assigned to
      have 1 mL dichloromethylene-diphosphonate (CL2MDP) or 1 mL NaCl 0.9% i.v. Forty
      eight hours later, all rats received a two-thirds liver resection. Twenty-four
      hours later, rats received at random 50 microg/kg endotoxin (LPS) in 1 mL or 1 mL
      of NaCl 0.9% IV. The rats were killed 4 hours after LPS or SAL infusion. RESULTS:
      CL2MDP infusion resulted in a complete KC elimination. KC-depleted rats had the
      lowest mean arterial pressure, the highest heart and ventilatory rate after
      endotoxemia. All rats were able to maintain pH in normal ranges. The KC-depleted
      rats after partial hepatectomy had the lowest CO2 levels and the highest levels
      of lactate during endotoxemia. Oxygen levels were similar in all groups. Hepatic,
      pulmonary, and renal mRNA expression of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1beta were decreased in KC-depleted rats. Plasma levels of TNF
      alpha were significantly decreased in KC-depleted rats. Furthermore, the highest
      influx of macrophages and polymorphonuclear cells in the lung and kidney were
      measured in KC-depleted rats during endotoxemia. CONCLUSIONS: Partial hepatectomy
      in KC-depleted rats result in a more pronounced endotoxin-mediated systemic
      inflammation and decreased synthesis of cytokines.

PMID- 15715275
TI  - T lymphocyte numbers in human gut associated lymphoid tissue are reduced without
      enteral nutrition.
AB  - BACKGROUND: Clinically, in the absence of enteral nutrition, the morbidity of
      infectious complication is high. Although experiments using mice have shown
      alterations in gut-associated lymphoid tissue (GALT) to be an important mechanism
      underlying impaired host defense, there are no clinical studies on the effects of
      nutritional routes on GALT. METHODS: A total of 27 colon cancer cases who
      underwent right colectomy or hemicolectomy were reviewed. Six patients did not
      receive enteral nutrition for 4 to 28 days before surgery because of bowel
      obstruction (parenteral nutrition [PNI group). Twenty-one patients were enterally
      fed before surgery (enteral nutrition [EN] group). The terminal ileum from
      resected specimens was examined microscopically. T-cell numbers in
      intraepithelial spaces (IE) and the lamina propria (LP) were determined
      immunohistochemically in blinded fashion. RESULTS: There were no significant
      differences in baseline characteristics between the 2 groups. T-cell number in
      the LP was significantly lower in the PN group than in the EN group, with no
      difference in IE cell numbers. CONCLUSIONS: Lack of enteral delivery of nutrients
      reduces GALT cell number in patients with colon cancer, as is the case in mice.

PMID- 15715276
TI  - The use of equations to estimate resting metabolic rate in critical care
      patients.

PMID- 15715277
TI  - Patient safety.

PMID- 15715279
TI  - [Drinking water decontamination with isolative sorbent disinfectants].
AB  - Drinking water can be decontaminated with the use of isolative sorbent
      disinfectants. Consideration of the effectiveness of water disinfectants and the
      sorptive power of porous materials against bacteria and viruses attested to the
      favour of iodine and silver-containing disinfectants and their compositions on
      porous aggressive carriers to be employed in extreme conditions such as on board
      crewed space vehicles.

PMID- 15715278
TI  - [Programmed death of the eukaryote cells].
AB  - The authors review literary and own data on programmed death of cells (PDC) in
      animals and plants, molecular mechanisms of apoptosis in animals, and key PDC
      regulating genes.

PMID- 15715280
TI  - [Nociceptive sensitivity and environmental factors].
AB  - The authors dwell upon the structure and functioning of the nociceptive system
      and modification of pain sensitivity by ambient factors like air temperature and
      atmospheric pressure.

PMID- 15715281
TI  - [Role of individual typological traits of employees charged with arduous duties
      in results of training in directed relaxation].
AB  - Results of training in directed relaxation were assessed based on the principle
      of biological feedback (BF). The psychophysiological status and balance of the
      key sympathetic control pathways were shown to undergo changes in the course of
      training.

PMID- 15715282
TI  - [New methods of evaluation of the human-operator reliability].
AB  - New methods to evaluate the human operator reliability were tested with
      participation of 27 students of the Air Traffic Control Faculty at the Civil
      Aviation Academy. One of the proposed criteria is reactivity of the sympathetic
      cardiovascular regulation as determined during a cold hypoxic-hypercapnic
      exposure. By this criterion, the subjects divided into a reactive and a super
      reactive group. Subjects of the "reactive " group demonstrated much better
      efficiency on a simulator, whereas subjects of the "super-reactive" group
      developed an inadequate sympathetic reaction to the rest-to-work transition
      revealed by a high activation of the parasympathetic component. Information
      perception was rated with the method of competing fields of vision aimed at
      evaluating the plasticity of the higher nervous system.

PMID- 15715283
TI  - [Effects of occlusive cuffs "Braslet" on crew hemodynamics in short space flights
      and orthostatic stability post flight].
AB  - Effects of prophylactic device Braslet (occlusive cuffs wrapped around the calf)
      on hemodynamics were studied at rest and during the LBNP test during and on
      orthostatic stability post short (one-month) space flights. The ultrasonic
      procedure was applied to seven cosmonauts who had and six cosmonauts who had not
      worn the cuffs while in orbit. The device markedly alleviated the subjective
      feeling of discomfort caused by blood shift toward the cranial end at the
      beginning of adaptation to microgravity. Reductions in the central and peripheral
      hemodynamics, cervico-cephalic venous plethora specifically, were sequel to
      staying in microgravity. Testing of the hemodynamic reactions to LBNP during and
      after shortflights failed to discover noticeable deltas among the cosmonauts who
      had and had not worn the cuffs. The first analysis of objective in- and
      postflight data did not suggest any determent in orthostatic stability of
      cosmonauts due to application of the Braslet cuffs.

PMID- 15715284
TI  - [Pursuit function of the eye during 7-day dry immersion without and with a
      support stimulator].
AB  - A computerized comprehensive investigation of the oculomotor system was performed
      following dry immersion of 12 human subjects deprived of or provided with support
      afferentation stimulation. The purpose was to determine effects of weak
      proprioceptive, tactile and support afferentation on the eye pursuit parameters
      and significance of the support input for the ocular function. Individual and
      general characteristics of spontaneous and induced oculomotor reactions were
      described and effectiveness of the eye tracking correction by stimulation of foot
      support afferentation during immersion was evaluated. The pursuit function was
      tested before the experiment (baseline data), in 3 hrs. since the beginning of
      immersion, on day 5 in immersion, shortly after and on day 3 of the completion of
      the experiment. The group of subjects without support stimulation exhibited
      marked omnidirectional deviations in the eye tracking parameters throughout the
      whole period of the experiment. In the group of subjects provided with support
      stimulation these parameters were but little different from baseline values. To
      conclude, a support stimulator stabilized the pursuit function of the eye making
      it less variant. However, there was no uniformity in the subjects' reaction to
      stimulation which infers that the methods of improving the eye pursuit function
      should be personally "molded".

PMID- 15715285
TI  - [Role of Mg2+ in keeping up the nonspecific immune functions of human neutrophils
      in vitro during hyperbaric exposure].
AB  - Earlier we have shown inhibition of the production by neutrophils of active forms
      of oxygen in humans exposed to high pressure. To get better understanding of the
      role of Mg2+ in the process, magnitude of the effect was assessed as a function
      of Mg2+ concentration using the activated hemiluminescent technique. It appears
      that in vitro production of active oxygen forms by blood neutrophils at high
      pressures can be sustained provided increased concentrations of Mg2+ in the
      incubating medium.

PMID- 15715286
TI  - [Spermatogenesis impairment by polychlorbiphenyls: endocrine and paracrine
      mechanisms of the damage].
AB  - Possible role of changed contents of certain cytokines in the genesis of
      reproductive disorders was studied in an experiment with rats intoxicated
      chronically by polychlorbiphenyl (PCB) ecopollutants at the total doses of 0.3
      g/kg of the body weight (0.05 LD50 and 3 g/kg of the body weight (0.5 LD50). The
      enzyme immunodetection was used to analyze blood serum, testicle tissues and
      sperm for interleukin-1beta, interleukin-6, interleukin-4, tumor necrosis factor
      alpha, and testosterone and estradiol. The experiment showed that chronic PCB
      intoxication significantly increases the production of pro-inflammatory cytokines
      and decreases the production of anti-inflammatory cytokines on a background of a
      sharp testosterone reduction and inversion of the androgen-estrogen profile.
      Implications of these shifts to steroido- and spermatogenesis are discussed along
      with cell and molecular mechanisms of cytokine-mediate PCB intoxication.

PMID- 15715287
TI  - [Remodeling of the actin cytoskeleton of cultivated human endothelium cells
      during clinostatting].
AB  - Architectonics of the fibrillar actin in cultures of human endothelium cells (EC)
      during and after extended (144 hrs.) clinostatting was examined under the
      fluorescent microscope. In control EC cultures, F-actin was composed of a network
      of filaments located both in the center and along the periphery of cells. One
      hour of rotation did not visibly affect the actin skeleton, however, in two hours
      there were cells with filaments displaced toward the membrane. Twenty-four hours
      of rotation caused total remodeling of the cytoskeleton so that practically the
      whole population of thin filaments had migrated toward the periphery. In most of
      the cells the intercell contact area formed undulating edges rich in F-actin. A
      similar picture could be seen after 144 hrs. of rotation. The actin skeleton
      partially recovered in 4 hrs. and regained the normal structure in 24 hrs. of
      rehabilitation. Same period was required for cells to restore their structure
      completely following the extended clinostatting. These data suggest sensitivity
      of the EC cytoskeleton to changes in the gravity vector. Remodeling of the actin
      skeleton in a changed gravity is reversible and proceeds more rapidly than
      recovery.

PMID- 15715288
TI  - [Is endemic hepatitis E infection present in developed countries?--Accumulating
      information about the hepatitis E virus and hepatitis E infection].
AB  - There are several new data on the acute viral hepatitis particularly on
      infectious non-A-non-C hepatitis viruses. The hepatitis E virus infection was
      originally thought to be limited only for certain geographic areas and humans.
      Recently, it has been demonstrated the genetic diversity and worldwide
      distribution of hepatitis E virus in human population, as well as, the
      circulation of the virus in many species of animals. It is evident, that
      hepatitis E virus can spread by fecally contaminated water (waterborne
      transmission), by meat of infected animals (food-borne transmission), by animal
      human contact (zoonotic transmission), and even by transfusion (blood-borne
      transmission). The frequency of hepatitis E virus infections among the acute
      hepatitis cases with unknown origin is supposed to be more than 10%. In the
      differential diagnosis of hepatitis, possible hepatitis E virus infection must be
      now taken into account even in those areas and countries, like in Hungary, where
      the infection was previously thought to be non-endemic. To confirm the clinical
      diagnosis of hepatitis E virus infection, virus specific ELISA and molecular
      methods are now available. In the near future, a molecular epidemiological study
      will be organized for the detection of hepatitis E virus in Hungary in
      collaboration with 9 European countries.--This review covers all aspects of the
      hepatitis E virus infection including the characteristics and transmission of the
      etiological agent, the clinical symptoms, its epidemiology, laboratory diagnosis,
      and some possible control measures.

PMID- 15715289
TI  - [Clopidogrel in the prevention of stroke].
AB  - Ischemic heart diseases continue to be leading causes of death throughout the
      world. Blood platelets play a pivotal role not only in haemostasis but also in
      the pathogenesis of thrombosis and atherosclerosis, platelet aggregation being an
      essential step in the formation of either an effective haemostatic plug or an
      intravascular thrombus. The benefits of various antiplatelet therapies ranging
      from aspirin, ticlopidine, Clopidogrel, and intravenous platelet GPIIb/IIIa
      antagonists in various thromboembolic disorders are well documented. The studies
      of CAPRIE, CURE, PCI-CURE and MATCH have shown that the clopidogrel has a highly
      advantageous preventive effect in the ischaemic vascular diseases, that is why
      clopidogrel be highly recommended in the stroke prevention.

PMID- 15715291
TI  - [Critical evaluation of clinical trials].
AB  - The primary source of scientific evidence are well designed and well executed
      randomised controlled clinical trials. However, the sources of scientific
      evidence are multifaceted. The concept of evidence based medicine is wider,
      encompassing the best available scientific data, the preference of patients and
      the professional experience of physicians. Decisions on therapies or other types
      of interventions are based on these three components. The authors give an
      overview of the evaluation of the results of randomised controlled clinical
      trials and present an easily applicable assessment list for practising
      physicians.

PMID- 15715290
TI  - [Ghrelin: a new peptide regulating the neurohormonal system and energy
      homeostasis].
AB  - Ghrelin: a new peptide regulating the neurohormonal system and energy
      homeostasis. Research leading to the identification of ghrelin started with the
      discovery of growth hormone secretagogues, continued with the description of
      ghrelin receptors and ended with description of the chemical structure of
      ghrelin. However, several aspects concerning the role of ghrelin in physiology
      and pathophysiology are still under investigation. The majority of ghrelin is
      produced in the stomach, but it is also expressed in the hypothalamus, pituitary,
      intestine, kidney, heart, pancreas and gonads. Ghrelin stimulates growth hormone
      secretion via growth hormone secretagogue receptors, and it increases appetite.
      Ghrelin secretion in the stomach depends on both acute and chronic changes in
      energy balance. Presently available data support the hypothesis that the stomach,
      in addition to its important role in digestion, not only influences pituitary
      hormone secretion via ghrelin production but it also sends orexigenic (appetite
      increasing) signals to hypothalamic nuclei involved in the regulation of energy
      homeostasis. In addition to these main effects, ghrelin influences the
      cardiovascular, gastrointestinal, reproductive and endocrine functions. It can be
      anticipated that further research on the physiological and pathophysiological
      role of ghrelin will lead to a better understanding of neurohormonal processes
      and the central regulation of energy homeostasis.

PMID- 15715292
TI  - [Effect of melatonin on intractable epilepsies].
AB  - The role of melatonin in human physiology until the second part of XX. century
      was unknown. The effects of melatonin have been studied in many physiological or
      pathological states of humans. There is now evidence that melatonin may have a
      role in many different actions, such as sleep promotion, control of biologic
      rhythm, mood, reproduction, tumor growth and aging. The authors report about the
      administration of melatonin for two pediatric epileptic patients, who suffer from
      intractable epilepsy. Their epilepsy was early onset, and different
      anticonvulsive treatments have been administered for them for many years,
      ineffectively. However, in response to 3 mg melatonin co-medication (administered
      in the evenings 30 min before patient's habitual bedtime) suppression of seizure
      activity has been shown on the EEG record of both children, and the number of
      their convulsions reduced clinically too. 3 month later the melatonin co
      medication was stopped. The seizures appeared again.

PMID- 15715293
TI  - [Long-term management after myocardial infarction (Part 1.): Lifestyle
      modifications].

PMID- 15715294
TI  - [Clinical electrocardiography in Hungary].

PMID- 15715295
TI  - Spiers Memorial Lecture. Recent experimental advances in studies of liquid/liquid
      interfaces.
AB  - Liquid/liquid interfaces play a key role in many important processes. Studying
      the molecular structure and interactions that occur at these interfaces can aid
      in our understanding of more complicated processes such as molecular transport
      across cell membranes. A variety of techniques have been applied to this pursuit.
      Here we present selected examples of exciting recent studies using different
      techniques to examine liquid/liquid interfaces.

PMID- 15715296
TI  - X-ray studies of the interface between two polar liquids: neat and with
      electrolytes.
AB  - We demonstrate the use of X-ray reflectivity to probe the electron density
      profile normal to the interface between two polar liquids. Measurements of the
      interfacial width at the neat nitrobenzene/water and the neat water/2-heptanone
      interfaces are presented. These widths are consistent with predictions from
      capillary wave theory that describe thermal interfacial fluctuations determined
      by the tension and bending rigidity of the interface. Variation of the
      temperature of the water/nitrobenzene interface from 25 degrees C to 55 degrees C
      indicates that the role of the bending rigidity decreases with increasing
      temperature. X-ray reflectivity measurements of the electrified interface between
      an aqueous solution of BaCl2 and a nitrobenzene solution of TBATPB demonstrate
      the sensitivity of these measurements to the electrolyte distribution at the
      interface. A preliminary analysis of these data illustrates the inadequacy of the
      simplest, classical Gouy-Chapman theory of the electrolyte distribution.

PMID- 15715297
TI  - Orientational order of the water molecules at the vicinity of the water-benzene
      interface in a broad range of thermodynamic states, as seen from Monte Carlo
      simulations.
AB  - Monte Carlo simulation of the water/benzene liquid-liquid interfacial system has
      been performed at six different thermodynamic state points, ranging from ambient
      conditions up to the vicinity of the critical point of water. The system has been
      found to consist of two immiscible liquid phases at every state point studied.
      The orientational preferences of the interfacial water molecules have been
      analysed in detail using the simulated configurations. The results obtained at
      ambient conditions are in agreement with previous results on various different
      water/apolar interfaces. Thus, interfacial water molecules have been found to
      have dual orientational preferences: the molecules located nearest to the organic
      phase prefer to stay perpendicular to the interface, pointing flatly toward the
      apolar phase by their dipole vectors, whereas the waters located somewhat farther
      from the organic phase prefer the parallel alignment with the interface. The
      observed orientational preferences are found to be rather stable with changing
      thermodynamic conditions: although the increase of the temperature has led, due
      to the increasing thermal motion of the molecules, to a gradual weakening of the
      orientational preferences, both preferences are found to exist up to at least 450
      K, and found to be completely washed out at 575 K only. The pressure has not been
      found to influence the orientation of the water molecules noticeably.

PMID- 15715298
TI  - Photo-induced ion transfer across the liquid/liquid interface.
AB  - Traditional studies of ion transfer across the interface between two immiscible
      liquids involve the establishment of a steady-state ion current across the
      interface. The data obtained from these studies are used to develop models of the
      interfacial kinetic. However, this approach, while straightforward to implement
      experimentally, is not sensitive to the microscopic structure of the interface
      region, which is only a few nanometers in size. We propose and examine the
      feasibility of a more direct approach to elucidating the ion dynamic by reporting
      the results of equilibrium and non-equilibrium molecular dynamics calculations in
      which an iodine ion is created at the interface between water and CCl4 by
      photodissociation of an adsorbed I2-. In this paper, we describe the model,
      examine the associated free energy curves and discuss the recombination of the
      parent molecule and its vibrational relaxation as a competing process for the ion
      transfer process.

PMID- 15715299
TI  - Simulation of interfaces between room temperature ionic liquids and other
      liquids.
AB  - The structure and properties of the interfaces between the room temperature ionic
      liquid dimethylimidazolium chloride ([dmim]Cl) and different Lennard-Jones fluids
      and between ionic liquid and water have been studied by molecular dynamics
      simulations, and compared to the ionic liquid-vapour interface. Two contrasting
      types of interface were investigated, thermodynamically stable interfaces between
      ionic liquid and vapour and between ionic liquid and Lennard-Jones fluids, and
      diffusing interfaces between miscible phases of different compositions involving
      water. The density profiles of different species through the interface are
      presented. The cations and water molecules near the former type of interface are
      aligned relative to the surface, but no orientational preference was found near
      or in the broad diffusing interface. The ionic liquid has a negative
      electrostatic potential relative to vapour or Lennard-Jones fluid, but is more
      positive than pure water. This contrast is explained in terms of the relative
      importance of orientation and concentration differences in the two types of
      interface.

PMID- 15715300
TI  - Surface charge effects on solvation across liquid/liquid and model liquid/liquid
      interfaces.
AB  - Resonance enhanced second harmonic generation (SHG) coupled with novel
      solvatochromic surfactants has been used to explore solvation across
      liquid/liquid interfaces in the presence of excess surface charge in the aqueous
      phase. The surfactants--dubbed "molecular rulers"--consist of hydrophobic,
      solvatochromic chromophores connected to charged headgroups via variable length
      alkyl spacers. Interfacial dipolar width is monitored as a function of
      chromophore/headgroup separation. Data show that cationic and anionic surfactants
      of equivalent lengths sample very different environments across a
      water/cyclohexane interface. The effective excitation wavelengths of cationic
      surfactants are shifted persistently to higher energies than in bulk cyclohexane
      while anionic surfactants solvation converges smoothly from the aqueous to the
      organic limit with increasing spacer length. To further evaluate the effect of
      surface charge on interfacial solvation, SHG was used to probe the environment
      surrounding molecular ruler chromophores adsorbed to the aqueous liquid/vapor
      interface in the presence of densely packed monolayers of 1-octanol. These
      monolayer systems are shown to reproduce qualitatively many of the features
      associated with bulk water/alkane interfaces and are logistically easier to
      assemble. Changing the ionic strength of the underlying aqueous sub-phase
      suggests that the headgroup of cationic molecular ruler surfactants alters the
      electronic structure of the chromophore rather than properties of the surrounding
      nonpolar environment.

PMID- 15715301
TI  - NMR study of lithium ion in nitrobenzene/water system.
AB  - The goal of this project has been to elucidate the solvation states and kinetics
      involved in the transfer of Li ions between nitrobenzene and water. A large
      interface area has been realized by confining one phase in polymer beads and
      suspending them in the other phase. A 2D 7Li-NMR spectroscopic result of such a
      system obtained on a 400 MHz instrument has shown that the rate of the Li ion
      transfer exchange between nitrobenzene and water is too fast to resolve
      individual solvatomers. A pair of well-resolved 7Li-NMR peaks corresponding to
      different solvation environments of Li+ in "wet" nitrobenzene has been observed.
      The most surprising result is that the ratio of those two peaks and their
      separation changes over a period of days, but it can be reversibly changed by
      mechanical disturbance, such as ultrasonication. This effect is reproducible and
      suggests spontaneous but slow formation of metastable solvatomers of Li+. Another
      surprising observation has been slow and irreversible incorporation of lithium
      ion from wet nitrobenzene into the walls of the silica-containing vessels.

PMID- 15715302
TI  - Interaction forces between oil-water particle interfaces--non-DLVO forces.
AB  - The interaction force between a rigid silica sphere and a butyl or octyl acetate
      droplet was measured in an aqueous environment using atomic force microscopy
      (AFM). The force measurements were performed without added stabilizers and the
      observed force behavior was found to be dependent on the type of inorganic
      electrolyte present, where the interfacial tension was constant over the
      electrolyte concentration range used. Force measurements in the presence of
      sodium nitrate showed repulsion at all concentrations. Force measurements in the
      presence of calcium nitrate or sodium perchlorate exhibited an initial repulsion
      followed by an attraction resulting in a mechanical instability in the AFM
      cantilever, termed jump-in. The force behavior observed was independent of the
      water solubility of the organic liquid, in that the same force-distance
      characteristics were obtained for slightly water soluble butyl acetate and the
      water sparingly soluble octyl acetate droplets. Modeling of the drop profile
      during particle-droplet interactions for this type of AFM measurement showed that
      the force-distance data for the sodium nitrate system obeys typical DLVO
      interactions. The disagreement between the DLVO predictions for the sodium
      perchlorate and calcium nitrate systems is attributed to a specific ion effect at
      the liquid-liquid interface, which gives rise to an attraction force that is
      greater than the electrostatic double layer repulsion over the length scale of 5
      to 10 nm.

PMID- 15715303
TI  - Surface rheology as a tool for the investigation of processes internal to
      surfactant adsorption layers.
AB  - The description of adsorption at liquid interfaces has been largely improved
      after incorporation into models of dynamic processes internal to the adsorption
      layers, such as surfactant re-orientation, aggregation and chemical reactions.
      Evidence for most of these processes has been given by qualitative studies
      utilising direct imaging techniques or by tensiometric investigations. These
      processes strongly influence the dilational rheological features of the
      adsorption layer, i.e. the response of interfacial tension to perturbations of
      the interfacial area. The investigation of the dilational rheology is then very
      effective to assess the existence of these processes and to characterise their
      kinetic parameters and equilibrium properties. To this aim specific models and
      experimental techniques have been recently developed. Here the surface visco
      elasticity of adsorbed surfactant layers, epsilon, at liquid-air and liquid
      liquid interfaces is measured by means of different oscillating drop/bubble
      methods, which are based on the interfacial tension response to harmonic
      perturbations of the interfacial area and have been implemented in capillary
      pressure and in drop shape tensiometers. The comparison of this data with
      theoretical predictions allows at the same time the validation of the models and
      the quantification of the kinetic features of the internal processes.

PMID- 15715304
TI  - Observation of interfacial tension minima in oil-water-surfactant systems with
      laser manipulation technique.
AB  - A laser beam passing through a liquid interface results in a deformation on the
      nanometer scale that is inversely proportional to the interfacial tension. Based
      on this principle, we developed a method to measure the liquid-liquid interfacial
      tension. The displacement excited by the pump laser is measured with another
      probe laser in a non-contact and non-destructive manner. The motion of the
      interface in response to the modulated intensity of the pump laser shows a
      characteristic spectrum yielding an accurate value of the interfacial tension.
      The new method is quite appropriate in the measurement of very low interfacial
      tension, and we applied it to the oil-surfactant-water system. First, we observed
      the change in the interfacial tension depending on the NaCl concentration in
      heptane and a water system containing AOT as a surfactant. The interfacial
      tension had a minimum value, approximately 1 microN m(-1), for a certain
      concentration of NaCl. Secondly, the measurement of the ultra-low interfacial
      tension was carried out changing the temperature of the same system. In this
      experiment, the critical decrease in the tension was observed near temperature
      ranges where the microemulsion phase spontaneously appeared. The minimum of the
      interfacial tension was interpreted as the critical phenomenon close to the
      second order phase transition. The critical exponent of the interfacial tension
      obtained from the results is v approximately 1.5, which is the same as that
      expected from the mean field theory for the binary mixtures. The experiments
      successfully demonstrated that this method should be a new tool to study various
      interfacial phenomena. As another demonstration, we measured the response spectra
      on the colloidal liquid surface. The results show that the surface tension of a
      colloidal liquid is the same as that of pure water.

PMID- 15715305
TI  - Structural studies of amphiphiles adsorbed at liquid-liquid interfaces using
      neutron reflectometry.
AB  - We report the application and refinement of a recently developed method for
      structural studies at a liquid liquid interface using neutron reflectometry. The
      technique involves the entrapment of a thin oil layer between a silicon substrate
      and an aqueous subphase. The thin oil film is prepared by spin-coating an oil
      film on to an oleophilically treated silicon substrate. During the reflectivity
      measurement the sample is maintained in a horizontal position, and the angle of
      incidence of the neutron beam is varied using a supermirror. Attenuation of
      neutron reflectivity at the lowest angle of incidence is used to determine the
      oil-layer thickness. We report information regarding the structure at the
      interface between hexadecane and a 0.1% w/v aqueous solution of the triblock
      copolymer Pluronic L64 with EO13PO30EO13 (EO = ethylene oxide; PO = propylene
      oxide) and the interface between hexadecane and a 3.7 mmol dm(-3) (approximately
      critical micelle concentration) aqueous solution of the cationic surfactant
      tetradecyltrimethylammonium bromide (C14TAB). For the C14TAB system, the
      reflectivity data unambiguously reveal the presence of a region highly
      concentrated in C14TAB on the oil side of the interface. For the Pluronic L64
      system, the data suggest that the polymer adsorbs at the interface occupying both
      oil and water sides of the interface. Model scattering length density profiles
      that capture these features are presented and further models that better fit the
      data are discussed.

PMID- 15715306
TI  - Gibbs energies of transfer of chiral anions across the interface water/chiral
      organic solvent determined with the help of three-phase electrodes.
AB  - For the first time the differences in free energies have been experimentally
      determined for the solvation of two enantiomeric ions in two enantiomeric
      solvents. Three-phase electrodes consisting of a droplet of a solution of
      decamethylferrocene in a chiral solvent (D- and L-2-octanol) attached to a
      graphite electrode and immersed in an aqueous solution containing chiral anions,
      allow the measurement of these data for the transfer of the enantiomeric ions
      across the water/chiral solvent interface. In all studied combinations the Gibbs
      energy to transfer an L-ion from water to the L-solvent was equal to the Gibbs
      energy of transfer of the D-ion from water to the D-solvent, and the same was
      found for the transfer of a L-ion from water to the D-solvent and for the D-ion
      from water to the L-solvent. In all cases, the combinations D-anion/D-solvent and
      L-anion/L-solvent have smaller standard Gibbs energies than the combinations D
      anion/L-solvent and L-anion/ D-solvent. This can be explained by less favourable
      interactions between an anion and a solvent molecule in the latter cases.

PMID- 15715308
TI  - Using the dynamic, expanding liquid-liquid interface in a Hele-Shaw cell in
      crystal growth and nanoparticle assembly.
AB  - The liquid-liquid interface has been used with considerable success in the
      synthesis of advanced materials ranging from (bio)minerals to inorganic membranes
      to nanoparticles. In almost all such cases, the interface is static. The Hele
      Shaw cell in which a viscous fluid is displaced by a less viscous one in a
      constrained manner has been invaluable in the study of dynamic instabilities at
      interfaces and in the study of viscous fingering pattern formation. However, the
      potential of the Hele-Shaw cell in carrying out reactions at the interface
      between the two fluids leading to the formation of inorganic materials has been
      largely unrecognized and underexploited. Realizing that the dynamic liquid-liquid
      interface in a Hele-Shaw cell would provide opportunities to control a variety of
      time-scales associated with material formation, we have started a program on the
      use of the Hele-Shaw cell in materials synthesis. In this discussion paper, we
      present some of our recent results on the growth of calcium carbonate crystals in
      the Hele-Shaw cell by the reaction of Ca2+ ions electrostatically complexed with
      carboxylate ions pinned to the interface with carbonate ions present in the
      aqueous part of the biphasic reaction medium. We show that both polymorph
      selectivity and the morphology of the crystals may be modulated by varying the
      experimental conditions in the cell. We also discuss the possibility of using the
      dynamic interface in the Hele-Shaw cell to cross-link gold nanoparticles in water
      through bifunctional linkers present in the oil phase and investigate the nature
      of the structures formed.

PMID- 15715307
TI  - Biocomposite films synthesized at a fluid/fluid interface.
AB  - In the synthesis of mesostructured particles and films, the cooperative self
      organization of amphiphilic molecules in the presence of reactive species is a
      key factor in the reaction mechanism. This paper presents a method for preparing
      structured collagen films synthesized at fluid/fluid interfaces. This work is an
      extension of previous efforts in our group to synthesize structured silica films
      in a reaction system confined at the interface between two immiscible fluid
      phases, providing an additional level of control over the structural evolution
      that occurs during reaction. Synthesis at a liquid/liquid interface was shown to
      provide excellent control over the mesostructure of the final product, avoiding a
      major problem encountered in many film synthesis techniques in which the reaction
      occurs at a liquid/solid interface: namely, the undesired effect of the solid
      surface on the film structure. The focus of this paper is the synthesis of
      structured composite films containing amphiphilic phospholipids and collagen.
      These films provide a way to pattern cell growth on biocompatible surfaces and a
      model system for studying the self-assembly mechanism of lipids and collagen.
      Self-assembled monolayers and bilayers composed of phosphatidylethanolamine (PE)
      lipids and collagen were investigated to determine how regularly patterned films
      can be prepared in a manner that preserves the bioactive properties of the
      collagen. Mixtures of PEs and acid-soluble collagen were spread on an aqueous
      subphase in a Langmuir trough. Surface pressure-area compression isotherms for
      the composite lipid/collagen monolayers provide information about interactions
      between these components. Langmuir-Blodgett (LB) techniques were utilized to
      transfer the composite films onto freshly cleaved mica. The mica-supported films
      were characterized by atomic force microscopy. The lipid/collagen ratio in the
      composite films was found to be the most important factor in determining how the
      collagen is assembled and distributed. The temperature and pH of the aqueous
      subphase, the process for spreading collagen on the subphase, the deposition
      speed, and the deposition pressure are factors that can be used to selectively
      control the film patterning. For most of these experimental factors, the range
      over which a highly structured uniform film can be fabricated over significant
      length scales is generally very narrow. Based on the experimental results and
      understanding of the fundamental interactions involved, a mechanism for the co
      self-assembly of phospholipids and collagen is suggested. The adhesion and growth
      of Chinese hamster ovary (CHO) cells on the patterned film surfaces demonstrates
      the biocompatibility of these composite films.

PMID- 15715309
TI  - Ion transfer processes at 4-(3-phenylpropyl)-pyridine/aqueous
      electrolyte/electrode triple phase boundary systems supported by graphite and by
      mesoporous TiO2.
AB  - Biphasic electrode systems allow electrochemical reactions to be driven in a
      microphase of organic liquid (typically 1-100 nL), which is coupled via ion
      transfer processes to the surrounding aqueous electrolyte medium. Microdroplet
      deposits on basal plane pyrolytic graphite as well as thin film deposits of the
      organic phase within a mesoporous titanium oxide host film are investigated.
      Cobalt tetraphenylporphyrin (CoTPP) is dissolved in the organic liquid 4-(3
      phenylpropyl)-pyridine (PPP) and deposited in the form of microphases at suitable
      electrode surfaces. The electrode is immersed in aqueous electrolyte
      environments. It is shown that two stable and highly reversible one-electron
      metal-centred redox processes occur consistent with Co(III/II)TPP and Co(II/I)TPP
      in the presence of axial pyridine ligands. The electrochemical characteristics
      for both processes are strongly affected by the liquid/liquid ion exchange
      accompanying the redox processes. The potential for both the Co(III/II)TPP and
      the Co(II/I)TPP redox processes can be adjusted independently by the choice of
      the nature and concentration of the aqueous electrolyte. The reversible potential
      observed for the CoTPP metal complex is dominated by the Gibbs energy of transfer
      for the 'spectator ions'. Conditions can be chosen to eliminate ion transfer
      effects on the potential scale for biphasic oxidation and reduction processes.

PMID- 15715310
TI  - Phase separation of water-alcohol binary mixtures induced by the
      microheterogeneity.
AB  - The relationship between liquid-liquid phase separation and microheterogeneity in
      water-primary alcohol mixtures was examined by analysing the mass spectra of
      clusters generated through the fragmentation of liquid droplets. By comparing the
      cluster structures of water-ethanol, -1-propanol, and -1-butanol binary mixtures
      at various alcohol concentrations, we discovered differences in the molecular
      clusters that control phase separation. We also studied the role of water in
      alcohol self-association. Alcohol self-association is promoted in the presence of
      a small amount of water (ca. 10 approximately 20 wt%), in which the water-water
      hydrogen-bonding network is weak and does not contribute to alcohol self
      association. We have demonstrated that alcohol self-association is also promoted
      by non-ideal mixing with other alcohols. The self-association of alcohol
      molecules complements the loss of stabilization energy caused by the relatively
      weak coexisting interactions. This complementary relationship among
      intermolecular interactions is an inherent property of solutions, and plays a key
      role in the phase separation process.

PMID- 15715311
TI  - Enzyme hyperactivity in AOT water-in-oil microemulsions is induced by 'lone'
      sodium counterions in the water-pool.
AB  - Water-in-oil microemulsions are thermodynamically stable single-phase dispersions
      of water and surfactant within a continuous oil phase. The classical ternary
      system, based on the surfactant sodium bis(2-ethylhexyl)sulfosuccinate ('AOT'),
      water and an alkane such as n-heptane, is an optically transparent monodispersion
      of spherical water-droplets coated with a close-packed surfactant monolayer and
      the droplet radius is, to a good first approximation, directly proportional to
      the molar water: surfactant ratio, R. Enzymes dissolved in the water droplets
      retain activity and stability. These systems have attracted interest as media for
      biotransformations. Principally based upon studies in AOT-stabilized w/o
      microemulsions, a peculiar feature of the kinetics of enzyme-catalyzed reactions
      has long been apparent: the reaction rate characteristically increases from
      around zero at R=3, through a maximum, in the range R= 10-20, and thereafter
      decreases again, so that plots of rate vs. R are characteristically 'bell
      shaped'. Furthermore, at optimal R, enzymes seem to be 'hyperactive', i.e., they
      are more active, by a modest but significant factor of 2-3-fold, than in aqueous
      solution. In this paper we propose the hypothesis that this kind of R-dependence
      arises because of the presence of freely mobile lone surfactant counterions (Na+)
      within the water-pool. These ions have no charge partners within the water pool
      and consequently have a high electrochemical potential. According to our model,
      lone counterions facilitate the hydrolysis of ester or amide substrates, for
      example, by stabilizing the tetrahedral intermediate formed during the reaction
      through ion-pairing with the carbonyl oxygen of the substrate, thus facilitating
      transfer of negative charge from the carbonyl carbon as it is attacked by the
      incoming nucleophile. An expression for the relationship between the
      concentration of free counterions in the water-pool and the compositional
      parameter R leads directly, through Debye-Huckel theory, to an expression for the
      relationship between the reaction rate and R, log k(R)= log k(o) + C(1/R)1/2
      where k(R) is the rate constant at some finite R, k(o) is the rate constant
      extrapolated to R = infinity and C is an R-independent coefficient. For enzymes
      that display bell-shaped kinetics, such as bovine alpha-chymotrypsin and
      Chromobacterium viscosum lipase, the descending part of the plot (i.e. from
      optimal R to high R) obeys this equation very well. Inspection of the above
      equation shows that the rate constant, k(R) is greater than k(o). Furthermore it
      is reasonable to equate k(o) with k(aq), the aqueous solution value of k since
      the condition R = infinity may be equated with the condition of infinite dilution
      with respect to counterions, so eliminating their specific effect on the
      kinetics. It follows from the inequality, k(R) > k(o) approximately equal to
      k(aq), that the enzyme is 'hyperactive' in the microemulsion compared with
      aqueous solution. We show that this is indeed the case for the chymotrypsin
      catalyzed hydrolysis of N-trans-cinnamoylimidazole and the lipase catalyzed
      hydrolysis of 4-nitrophenyl acetate. The tailing off of enzyme activity at low R
      (< 10) is most likely due to conformational immobilization, probably due to
      partial dehydration in these low-water preparations (water activity, a(w), drops
      off rapidly below R = 15). We show that the reaction of glycylglycine with 4
      nitrophenyl acetate, a 'hyperactive' non-enzymic reaction, does not suffer from
      this effect and obeys the above equation across the whole range of R.

PMID- 15715312
TI  - Interfacial and mass transport enhancement effects on rates of styrene
      epoxidation catalyzed by myoglobin films in microemulsions.
AB  - Biocatalytic surfaces hold promise for future clean methods of chemical
      synthesis. Biocatalyst films utilizing inexpensive redox proteins can operate in
      low-toxicity microemulsions with high capacities to dissolve nonpolar reactants.
      Crosslinked films of myoglobin (Mb) and poly(L-lysine) (PLL) attached to oxidized
      carbon cathodes gave up to 40-fold larger turnover rates in bicontinuous
      microemulsions compared to o/w microemulsions and micelles. Larger synthetic
      turnover rates are correlated with up to 10-fold faster diffusion of solutes in
      oil phases of the bicontinuous fluids, as measured by voltammetry. Visible and
      circular dichroism spectra suggest that myoglobin resides in the film in a
      largely aqueous environment. The reactant sites in films monitored by a
      fluorescent probe were more polar when films were in CTAB than in SDS
      microemulsions. These combined results suggest that larger mass transport rates
      in the bicontinuous fluids is a major factor for enhanced turnover rates.
      Electrostatic interactions between the charged films and oppositely charged
      surfactants may significantly influence turnover rates when reactant mass
      transport is not fast enough.

PMID- 15715313
TI  - Antibiotic assisted molecular ion transport across a membrane in real time.
AB  - The transport of an organic cation across a 4-5 nm liposome bilayer is observed
      in real time using second harmonic generation. It is proposed that an
      electrostatic barrier between the inside and outside of the liposome develops as
      the cation crosses the bilayer. This would explain why the SHG signal does not
      approach zero at long times. To test this mechanism, the antibiotic valinomycin,
      which can transport alkali ions across a phospholipid bilayer, is introduced into
      the system. It is found that the transport time is reduced by a factor of three
      from 90+/-2 s to 30+/-1 s with 1.25 x 10(-8) M valinomycin concentration, and a
      factor of fifteen to 6.2+/-0.2 s with 1.25 x 10(-8) M valinomycin concentration.
      In addition, the SHG signal approaches zero, which further supports the presence
      of an electrostatic barrier that can be eliminated by the alkali ion transporter
      valinomycin.

PMID- 15715314
TI  - Dynamics of phospholipid monolayers on polarised liquid-liquid interfaces.
AB  - Quasi-elastic laser light scattering (QELS) is used to investigate dynamics of
      the polarised water/1,2-dichloroethane (DCE) interface in the presence of
      adsorbed DL-alpha-dipalmitoylphosphatidylcholine (DPPC) over a range of the
      interfacial potential differences (+/-0.3 V) and DPPC concentrations (0-20
      microM). An analysis of the frequency of thermally excited capillary waves
      reveals some novel features in the adsorption of DPPC. The effect of the
      capillary wavenumber on the capillary wave frequency and the damping factor
      suggest that the dynamic behaviour of ITIES is consistent with the theoretical
      predictions for a sharp liquid-liquid interface.

PMID- 15715315
TI  - Steady-state analysis of polymer adsorption at and transport across an interface
      between two polymer phases.
AB  - We consider a mutually incompatible polymer mixture composed of two major
      components AN and BN and a third minority component C(N). The interactions,
      parameterized by short-range Flory-Huggins interaction parameters, are chosen
      such that C wets the A/B interface completely at three-phase coexistence. At sub
      saturated conditions the adsorption of C remains necessarily microscopic. We
      study such a system in a stationary off-equilibrium state: due to imposed
      chemical potential gradients, polymer AN diffuses from the A-rich bulk phase
      through the interface to the A-poor bulk phase. Polymer BN travels in the
      opposite direction. Symmetric conditions are selected for which the polymer CN
      that accumulates at the A/B-interface has no net flux in the stationary state.
      This system is described by the Mean Field Stationary Diffusion (MFSD) model, an
      approach that solves the Scheutjens Fleer self-consistent-field (SF-SCF)
      equations with the boundary condition that the chemical potentials in the two
      bulk phases are different (but constant) so that a stationary state can be
      described. When the chemical potentials in the two bulk phases are the same, MFSD
      reduces to the equilibrium SF-SCF results. From the MFSD method we obtain the
      stationary volume fraction profiles and segmental fluxes. By forcing the system
      further from three-phase coexistence, i.e. by imposing larger concentration
      gradients, the adsorption of C goes unexpectedly from a thin adsorption layer to
      a thick adsorption film. The susceptibility partial differential J(A)/partial
      differential Delta(phi)A of the flux of A (equal to minus the flux of B) with
      respect to the imposed concentration gradient changes abruptly at the transition
      in adsorption behaviour. Interestingly, upon variation of the concentration
      gradients, the fluxes of A and B are enhanced by the accumulation of C at the
      interface. This means that the adsorbed C-film does not behave as an inert
      barrier.

PMID- 15715316
TI  - Fusion and fission of fluid amphiphilic bilayers.
AB  - The system water-oil (n-decane)-nonionic surfactant (C12E5) forms bilayer phases
      in a large concentration region, but, for a given oil-to-surfactant ratio, only
      in a narrow temperature range. In addition to the anisotropic lamellar phase
      (Lalpha) there is also, at slightly higher temperature, a sponge or L3-phase
      where the bilayers build up an isotropic structure extending macroscopically in
      three dimensions. In this phase the bilayer mid-surface has a mean curvature
      close to zero and a negative Euler characteristic. In this paper we study how the
      bilayers in the lamellar and the sponge phase respond dynamically to sudden
      temperature changes. The monolayer spontaneous curvature depends sensitively on
      temperature and a change of temperature thus provides a driving force for a
      change in bilayer topology. The equilibration therefore involves kinetic steps of
      fusion/fission of bilayers. Such dynamic processes have previously been monitored
      by temperature jump experiments using light scattering in the sponge phase. These
      experiments revealed an extraordinarily strong dependence of the relaxation time
      on the bilayer volume fraction phi. At phi < 0.1 the relaxation times are so slow
      that experiments using deuterium nuclear magnetic resonance (2H-NMR) appear
      feasible. We here report on the first experiments concerned with the dynamics of
      the macroscopic phase transition sponge-lamellae by 2H-NMR. We find that the
      sponge-to-lamellae transition occurs through a nucleation process followed by
      domain growth involving bilayer fission at domain boundaries. In contrast, the
      lamellae-to-sponge transformation apparently occurs through a succession of
      uncorrelated bilayer fusion events.

PMID- 15715317
TI  - Surface freezing of chain molecules at the liquid-liquid and liquid-air
      interfaces.
AB  - Surface freezing (SF) is the formation of a crystalline monolayer at the free
      surface of a melt at a temperature Ts, a few degrees above the bulk freezing
      temperature, Tb. This effect, i.e. Ts > Tb, common to many chain molecules, is in
      a marked contrast with the surface melting effect, i.e. Ts < or = Tb, shown by
      almost all other materials. Depending on chain length, n, the SF layer shows a
      variety of phases, in some cases tuneable by bulk additives. The SF behaviour of
      binary mixtures of different-length alkanes and alcohols is governed by the
      relative chain length mismatch, /delta n/n/2, yielding a quasi-"universal"
      behaviour for the freezing of both bulk and surface. While SF at the liquid air
      interface was studied rather extensively, Lei and Bain (Phys. Rev. Lett., 2004,
      94, 176103) have shown only very recently that interfacial freezing (IF) can be
      induced also at the water: tetradecane interface by adding the ionic surfactant
      CTAB to the water phase. We present measurements of the interfacial tension of
      the water: hexadecane interface, as a function of temperature and the ionic
      surfactant STAB, revealing IF at a STAB-concentration-dependent temperature Ti >
      Tb. The measurements indicate that a single frozen monolayer is formed, with a
      temperature-existence range of up to 10 degrees C, much larger than the 1.2
      degrees C found for SF at the free surface of the melt. We also find a new
      effect, where the IF allows tuning of the interfacial tension between the two
      bulk phases to zero for a range of temperatures, deltaT = Tmix - Tb < or = Ti -
      Tb by cooling the system below Ti. We discuss qualitatively the factors
      stabilizing the frozen layer and their variation from the liquid-air to the
      liquid-liquid interfaces. The surfactant concentration dependence of Ti is also
      discussed and a tentative theoretical explanation is suggested.

PMID- 15715318
TI  - Fighting stigma from with in.

PMID- 15715319
TI  - Making equity a reality: oral health promotion in a psychiatric setting.
AB  - The aim of the study addresses the inequity in oral health status of long stay
      psychiatric patients, by promoting an inter-disciplinary team approach to oral
      health promotion. A cross sectional study using a modified version of the oral
      health assessment guide (OHAG) (Eilers et al 1988, Sjorgen & Nordstrom 2000) was
      used by a nurse who received training and calibration at the School of Dentistry,
      Queen's University, Belfast, to assess the oral health status of long stay
      psychiatric patients. The paper provides an overview of the literature relating
      to oral health within the context of holistic health. It highlights the non
      random distribution of oral health problems amongst psychiatric patients and the
      potential contribution of health needs assessment to the realization of equity.
      The study focused on 65 long stay patients in a psychiatric hospital, mean length
      of time patients had been in the hospital was 25.6 years; nine patients had been
      living in the hospital between 40 and 65 years. The study achieved a response
      rate of 82% and identified that oral health of the psychiatric patients was
      generally very poor, compared to the general population. Only one patient did not
      have calculus, decayed or fractured teeth and 12 of the patients were endentate
      and there was a conspicuous absence of health promoting behaviours amongst the
      patient group. A case study is used to highlight the lived reality of the
      patients and the need for a holistic and an inter-disciplinary approach to oral
      health promotion, for patients residing in a psychiatric setting. This
      preliminary investigation highlights the benefits of systematic assessment of
      need: in this instance the use of the OHAG as a tool, for promoting equity based
      care by making visible the non random distribution of oral health problems
      amongst the patients.

PMID- 15715320
TI  - Insomnia, depression and anxiety disorders and their association with
      benzodiazepine drug use among the community-dwelling elderly: implications for
      mental health nursing.
AB  - Benzodiazepine (BZD) drug use among seniors is an important public health issue
      because the benefit from their use is moderate and of short duration and numerous
      adverse events have been linked to their use. Furthermore, there is a significant
      discrepancy between the prevalence of mental health disorders and BZD drug use in
      the elderly population, which can be attributed to a measurement issue. The goal
      of this cross-sectional descriptive study was to determine the prevalence of
      mental health disorders among seniors using BZD and living in the community,
      basing this information on both a thorough face-to-face interview and a pair of
      self-reported validated instruments. Among the 216 seniors recruited in our
      study, nearly 20 % were users of BZD and over three quarters of them had been
      using this drug for more than a year. Thirteen subjects were recognized as
      depressed according to a self-report measure compared to 18 according to the
      interview. Likewise, 13 seniors were categorized as anxious, based on a self
      report questionnaire compared to 39 based on the interview. Among self-reported
      measures of mental health variables, logistic regression indicated that insomnia
      increases by 7 the likelihood of using BZD (odds ratio: 7.2) and is the only
      statistically significant variable associated with BZD consumption. Based on
      thorough interviews, logistic regression showed that insomnia (odds ratio: 6.9)
      is still the dominant symptom associated with BZD drugs. In conclusion, our
      results clearly support the assertion that mental health status is influenced
      according to how it is measured. Finally, nurses should be aware that not all
      individuals are capable of expressing their mental health problems using either
      psychological or emotional terminologies. They may opt for expressing their
      psychological suffering as a physical symptom such as sleeping problems.

PMID- 15715321
TI  - Education for life: the evaluation of an innovative approach to facilitate
      ongoing learning for nurses.
AB  - There is general consensus within the nursing profession that life-long learning
      is crucial for all nurses irrespective of their educational backgrounds. There
      currently is a paucity of literature addressing both the problems experienced in
      accessing and utilising continuing education or innovative programs designed to
      overcome these problems, despite widespread acknowledgement of the problems
      encountered. In this paper the findings from the evaluation of the Clinician
      Trainer Program, developed by the Centre for Psychiatric Nursing Research and
      Practice (CPNRP) are presented. This includes an evaluation of the course itself
      and of its impact on clinical practice. The findings suggest a high level of
      satisfaction with the course, but more importantly, it appears to be assisting
      trained clinicians to deliver professional development sessions within their
      workplace.

PMID- 15715322
TI  - An overview of the assessment tools available to mental health professionals to
      help determine patients at risk of suicide.
AB  - Tools are frequently used in psychiatry in an attempt to assess the patient's
      mental state and this in turn should partly determine his management. A given
      example is suicide evaluation, where tools are regularly used but seldom
      questioned as to their effectiveness or appropriateness. At the outset, this
      paper highlights the relative paucity of research into suicide assessment scales
      and rationales are offered explaining this. Furthermore, attention is drawn to
      the concept that relatively low base rates of suicide can provide false and
      misleading data. Additionally, analyses are made of a number of suicide
      assessment scales and this is achieved through a comprehensive literature review
      on the subject area. The five pieces of research examined come from different
      parts of the world, however they all share a commonality in that they are Western
      in culture. Nevertheless, no obvious leader arises from the combined results,
      with all the scales offering different conclusions as to the most effective scale
      for evaluating those at risk of suicide. These contradictions may be due to the
      fact that the research design and methodology used in the studies has been ill
      thought out and omissions such as the use of qualitative data is discernible in
      studies that deal with human behaviour. The suggested recommendations provided
      include further research in this area and that it should include the use of
      qualitative methods. A further recommendation is that suicide assessment should
      encompass both the physical environment as well as the patient's mental health
      and this would help ensure a more encompassing and in-depth assessment of the
      patient. Nevertheless, assessment scales, no matter how thorough they appear,
      should not be seen as a panacea for determining the overall management of a
      patient.

PMID- 15715323
TI  - Nurses touching lives. Parish nursing.

PMID- 15715324
TI  - Depression in the older adult: recognition and nursing intervention.
AB  - The importance of identifying and intervening in elders with depression cannot be
      underestimated. The baby boom population is reaching the chronological milestone
      of being considered older age, which means that the percentage of older adults
      with depression will result in increased numbers of depressed older adults in all
      settings needing nursing care. Nurses must be able to recognize symptoms of
      depression, whether subsyndromal depression or major depression, to be able to
      intervene effectively. Depressive symptoms interfere with the quality of life and
      respond to nursing interventions that address psychosocial functioning including
      loss, educational strategies to increase understanding of depression as a
      disease, its treatment and adherence strategies, interventions that monitor and
      improve chronic medical illness, and recognize medication management that has the
      least likelihood of side effects. The importance of psychotherapies was not
      stressed above due to limitations in space, but in addition to problem solving
      therapy, cognitive and interpersonal supportive therapies are also effective.
      Electroconvulsive therapy is also effective in treating depression in the elderly
      when the patient is suicidal.

PMID- 15715325
TI  - The case for funder as customer.

PMID- 15715326
TI  - A response to stories about wait times for medical procedures.

PMID- 15715327
TI  - "Health in a global society: a Canadian perspective".

PMID- 15715328
TI  - INTERHEART: nine factors that could save your life.

PMID- 15715329
TI  - Safeguarding privacy: the ICES experience.

PMID- 15715330
TI  - EXTRA encourages cultural shift in Canadian healthcare.

PMID- 15715331
TI  - Canada's health system: transitions in leadership.

PMID- 15715332
TI  - Greening healthcare: looking back, looking forward.

PMID- 15715333
TI  - Evidence, interests and knowledge translation: reflections of an unrepentant
      zombie chaser.
AB  - Justice Emmett Hall's landmark 1964 Royal Commission report is remarkable as,
      among other things, a very early Canadian example of successful knowledge
      brokering. It predates by about three decades even the earliest discourse in
      Canadian health research circles about knowledge translation, knowledge transfer,
      knowledge exchange, knowledge brokers, and the like.

PMID- 15715334
TI  - Steering and rowing in healthcare: the devolution option.
AB  - Claims of"underfunding" notwithstanding, the problems we are experiencing with
      healthcare in Canada are primarily attributable to a deficiency of governance of
      our ill-coordinated non-system of health and healthcare services.

PMID- 15715335
TI  - Raising the bar for people practices: helping all health organizations become
      "preferred employers".
AB  - Human resources are the single largest budget line in any healthcare
      organization. But employees are not costs; rather, they must be viewed by
      managers, boards, and governments as the core assets of the system.

PMID- 15715337
TI  - Concordance, compliance and adherence in healthcare: closing gaps and improving
      outcomes.
AB  - The gap between best care and usual care is large for many important diseases. In
      particular, poor adherence remains a significant, inadequately addressed, cause
      of the care gap. About half of all patients with chronic diseases stop refilling
      prescriptions by one year. Several effective interventions are available and
      adaptations of clinical trials practices offer promise for further improvement.
      Poor adherence is a remedial problem in healthcare quality and its improvement
      and accountability offer shared opportunities for providers and patients. There
      is a large gap between best care, defined as the optimal use of proven
      efficacious therapies in whole populations at risk from any disease, and usual
      care, the actual level of efficacious care being provided (Montague et al. 1997).
      This gap in patient care has four main causes: diseases may not be diagnosed,
      efficacious therapies may not be prescribed, access to therapy may be restricted
      or patients may not adhere to prescriptions. Irrespective of causation, the
      ultimate result of care gaps is the same--less than optimal clinical outcomes and
      associated lost opportunities for improved quality of life and productivity.
      Systematic approaches to improving prescribing practices are increasing, and
      there is much debate around improving patients' access to care. Poor diagnosis is
      judged to be relatively uncommon, leaving decayed adherence as the major under
      addressed cause of care gaps and a major opportunity for improvement. This paper
      reviews the scope and causation of sub-optimal adherence, evaluates improvement
      strategies and explores a best-practice benchmark.

PMID- 15715338
TI  - Coming soon to a health sector near you: an advance look at the new Ontario
      Personal Health Information Protection Act (PHIPA): part II.
AB  - This is Part II of a two-part article that provides a broad overview and
      comparative study of the new Ontario health sector-specific privacy legislation.
      In Part I, which appeared in the previous issue of Healthcare Quarterly, we
      discussed the objectives, structure and scope of, as well as the substantive
      rights and obligations created by, the new Ontario Act. In Part II, we discuss
      the administrative obligations created by the Ontario Act, as well as the
      provisions relating to the enforcement of, and remedies available under, the Act.
      We also contrast the Ontario Act with the various approaches to the protection of
      personal health information that has already been adopted by other provinces,
      including Alberta, Saskatchewan and Manitoba.

PMID- 15715339
TI  - Leaders' forum on health research in Canada: the urgent need for innovation.
AB  - In the fall of 2003, the Council for Health Research in Canada (CHRC) formed a
      Leaders' Forum Steering Committee, a multi-sectoral partnership representing
      organizations and agencies at both the federal and provincial levels, that
      strongly believed it was time to bring health research leaders together to take
      stock of our accomplishments, identify our challenges and discuss future
      directions.

PMID- 15715340
TI  - Primary healthcare: the all-too-quiet revolution in waiting.
AB  - Remodelling the kitchen won't help the house with a weak foundation. The same
      holds truth in healthcare. We cannot solve quality and access problems or deal
      effectively with wait times unless primary healthcare the foundation of the
      system--is solid.

PMID- 15715341
TI  - Measuring information technology investment among Canadian academic health
      sciences centres.
AB  - Many recent studies have attempted to accurately measure the expenditure by
      hospitals in the area of new information technology (IT), for example see Leonard
      1998 and Pink et al. 2001. This is usually done as an exercise to compare the
      healthcare sector with other industries that have had much more success in
      implementing and leveraging their IT investment (Willcocks 1992; Chan 2000). It
      is normally hoped that such investigation would help explain some of the
      differences among the various industries and provide insight into where (and how
      much) future IT spending should occur in healthcare (Leonard 2004). Herein, we
      present the results from a study of eight Canadian academic health sciences
      centres that contributed data in order to analyze the amount of information
      technology spending in their organizations. Specifically, we focus on one
      specific indicator: the IT spend ratio. This ratio is defined as the percentage
      of total IT net costs to total hospital net operating costs, and aims to provide
      a "relative (or percentage) measure of spending" so as to make the comparisons
      meaningful. One such comparison shows that hospitals spend only 55% of the amount
      the financial services sector spends.

PMID- 15715342
TI  - First do no harm: Hamilton Health Sciences' experience as first hospital in the
      world to fully implement Medley Medication Safety System.

PMID- 15715343
TI  - War liver injuries.
AB  - AIM: To provide a retrospective analysis of our results and experience in primary
      surgical treatment of subjects with war liver injuries. METHODS: From July 1991
      to December 1999, 204 subjects with war liver injuries were treated. A total of
      82.8% of the injured were with the liver injuries combined with the injuries of
      other organs. In 93.7%, the injuries were caused by fragments of explosive
      devices or bullets of various calibers. In 140 (68.6%) of the injured there were
      minor lesions (grade I to II), treated with simple repair or drainage. There were
      complex injuries of the liver (grade III-V) in 64 (31.4%) of the injured Those
      injuries required complex repair (hepatorrhaphy, hepatotomy, resection
      debridement, resection, packing alone). The technique ofperihepatic packing and
      planned reoperation had a crucial and life-saving role when severe bleeding was
      present. Routine peritoneal drainage was applied in all of the injured. Primary
      management of 74.0% of the injured was performed in war hospitals. RESULTS: After
      primary treatment, 72 (35.3%) of the injured were with postoperative
      complications. Reoperation was done in 66 injured. Total mortality rate in 204
      injured was 18.1%. All the deceased had significant combined injuries. Mortality
      rates due to the liver injury of the grade III, IV and V were 16.6%, 70.0% and
      83.3%, respectively. CONCLUSION: Complex liver injuries caused very high
      mortality rate and the management of the injured was delicate under war
      circumstances (if the injured reached the hospital alive). Our experience under
      war circumstances and with war surgeons of limited knowledge of the liver surgery
      and war surgery, confirmed that it was necessary to apply compressive abdominal
      packing alone or in combination with other techniques for hemostasis in the
      treatment of liver injuries grade III-V, resuscitation and rapid transportation
      to specialized hospitals.

PMID- 15715344
TI  - [External skeletal fixation of the tibial shaft fractures].
AB  - AIM: To present the possibility of a succesfful use of external skelatal fixation
      in treating the open and closed tibial shaft fractures with Mitkovic's external
      fixator. METHODS: External fixation was used in 115 patients with 118 fresh
      tibial shaft fractures, 82 males (71.3%) and 33 females (28.7%), average age
      43.92 years (16-84). Open tibial shaft fractures were present in 37 (31.36%). All
      the fractures were treated with Mitkovic's external fixator type M 20. RESULTS:
      The results of external fixation were excellent or good in 94.07% of the cases,
      and bad in 5.08%. Pin tract infection appeared in 7 (5.93%) patients. In only 3
      cases an external fixator was removed and treatment continued with the functional
      braces. Nonunion occurred in 6 (5.08%) patients, of which 4 were with open
      fractures (2 Gustilo type IIIB, 1 Gustilo type IIIA, 1 Gustilo type II) and 2
      with the segment fractures. Compartment syndrome was observed in 1 (0.85%)
      patient with closed fracture. Malunion was found in 2 (1.69%) patients.
      CONCLUSION: External fixation of tibial shaft fractures is a simple and effective
      method to enable the safe healing of fractures, early mobilization of the
      patients, early weight-bearing, as well as early rehabilitation. Fixation of
      tibial shaft fractures was unilateral with convergent pins orientation, and there
      was also a possibility of compression and distraction.

PMID- 15715345
TI  - [Comorbidity of posttraumatic stress disorder and mild closed head injury in war
      veterans: endocrinological and psychological profiles].
AB  - AIM: To determine the degree of psychological and endocrinological changes in war
      veterans with the diagnosis of Chronic Posttraumatic Stress Disorder (PTSD)
      regarding presence/absence of comorbid mild closed head injury (mCHI) caused by
      explosive devices. METHODS: Two groups of PTSD inpatients, with (n = 37), and
      without (n = 86) sustained blast trauma followed by mCHI were formed during the
      psychiatric treatment. Participants were interviewed by experienced clinicians
      who used the PTSD Interview (PTSD-I). In addition, patients completed the Symptom
      Checklist-90-Revised (SCL-90-R). Serum levels of ten hormones were assessed:
      triiodothyronine, thyroxine, thyrotropin-stimulating hormone, prolactin,
      luteinizing hormone, follicle-stimulating hormone, and insulin, by
      radioimmunoassays and hydrocortisone, growth hormone and testosterone by
      fluoroimmunoassays. RESULTS: Veterans with comorbid mCHI and PTSD showed
      significantly higher level of amnesia for traumatic event as well as of
      somatization on the SCL-90-R. Significant differences of hormone levels were not
      found. CONCLUSION: The results didn't support the hypothesis on specific PTSD
      subgroup characterized by history of mCHI and consecutive postconcussion
      syndrome. The absence of differences in levels of hormones indicated the dominant
      role of psychogenic trauma in the etiology of hormone disbalance in chronic PTSD.
      Amnesia for traumatic event in war veterans with comorbid PTSD and mCHI was
      easily explained by neurogenic peritraumatic amnesia due to the blast trauma, but
      it did not affect either quality of intensity or posttraumatic symptoms as well
      as endocrinological parameters.

PMID- 15715346
TI  - [Spectral analysis of heart period variability in anorexia nervosa].
AB  - The aim of this study was to investigate the response of autonomic cardiac
      control to postural change using spectral analysis, in patients with anorexia
      nervosa. Spectral components of total variability as well as of low and high
      frequencies were analyzed for 17 anorexic patients with mean body mass index
      (14.9 +/- 1.9) kg/m2 and for 9 healthy age-matched women with body mass index
      (20.3 +/- 1.7) kg/m2 , in supine and standing postures. During standing posture,
      increased heart rate in all subjects was accompanied by the decrease in total
      variability and high frequency spectral powers. In supine posture, anorexic
      patients demonstrated the reduced low frequency spectral power. Compared to
      control women, during standing posture anorexic patients showed higher heart
      rate, reduced total variability and high frequency spectral powers. Statistically
      significant correlation was noticed between body mass index and spectral power of
      low frequency in both supine and standing posture. Alterations in autonomic
      cardiac control induced by anorexia nervosa could be estimated by spectral
      analysis of heart period variability.

PMID- 15715347
TI  - [Proliferative activity of myeloma cells determined by Ki-67 antibody: biological
      and clinical significance].
AB  - In this study we analyzed proliferative activity of myeloma cells and a possible
      correlation with selected clinical data, histological features and survival in 59
      patients with newly diagnosed multiple myeloma (27 females and 32 males, mean age
      62 years). Imunohistochemical method was applied using Ki-67 antibody on B5-fixed
      and paraffin-embedded bone marrow specimens to evaluate growth fraction of
      myeloma cells. Clinical staging was done according to the Durie-Salmon
      classification (4 patients had stage I disease, 16 patients stage II and 39
      patients stage III). The number of Ki-67+ myeloma cells ranged from 1% to 36%
      (mean value 7%). In 39 of 59 patients (66.1%) number of Ki-67+ cells was less
      than 10% (cases with low proliferative index). Ki-67 expression significantly
      correlated with the clinical stage, beta2-microglobulin level, plasma cell
      morphology, volume of myeloma infiltration and the extent of osteolytic lesions.
      Patients with increased proliferative index (Ki-67+ cells > or = 10%) showed a
      significantly shorter survival compared to those with low proliferative index (14
      months vs. 36 months, p = 0.023). However, this difference was not shown in
      multivariate analysis, particularly due to the high correlation between
      proliferative activity and plasma cell morphology and the volume of myeloma
      infiltration.

PMID- 15715348
TI  - [Detection of Helicobacter pylori in gastric biopsy and resection specimens].
AB  - AIM: To compare the sensitivity of detecting H. pylori in gastric biopsy and
      resection specimens using modified Giemsa stain and immunohistochemistry, using a
      commercially available anti-H. pylori antibody (Dako, Denmark). METHODS: Gastric
      antral biopsy specimens showing chronic gastritis (28 cases) together with tissue
      blocks from gastrectomy specimens for duodenal ulcer (2 cases) were stained with
      modified Giemsa and immunoenzymatic alkaline phosphatase - anti-alkaline
      phosphatase (APAAP) method, and were carefully examined for the presence of H.
      pylori. RESULTS: Using a modified Giemsa stain, the spiral shaped bacteria of H.
      pylori stained blue, were attached to the brush border of the gastric foveolar
      epithelial cells. However, the specificity of modified Giemsa stain depended on
      the morphological appearance of H. pylori. The specificity of immunostaining
      permitted detection of low numbers or even single organisms. In all cases
      bacteria were more prominent and easier to detect in immunostained preparations.
      H. pylori was identified in 22 (73.3%) of 30 sections stained with modified
      Giemsa stain, but it could be identified with greater frequency in sections
      stained with APAAP, in 27 (90%) of 30 sections. CONCLUSION: Immunohistochemical
      identification of H. pylori was better than Giemsa stain for detecting that
      organism.

PMID- 15715349
TI  - [The level of the sciatic nerve division and its relations to the piriform
      muscle].
AB  - BACKGROUND: The sciatic nerve, as the terminal branch of the sacral plexus,
      leaves the pelvis through the greater sciatic foramen beneath the piriform
      muscle. Afterwards, it separates into the tibial and the common peroneal nerve,
      most frequently at the level of the upper angle of the popliteal fossa. Higher
      level of the sciatic nerve division is a relatively frequent phenomenom and it
      may be the cause of an incomplete block of the sciatic nerve during the popliteal
      block anesthesia. There is a possibility of different anatomic relations between
      the sciatic nerve or its terminal branches and the piriform muscle (piriformis
      syndrome). The aim of this research was to investigate the level of the sciatic
      nerve division and its relations to the piriform muscle. It was performed on 100
      human fetuses (200 lower extremities) which were in various gestational periods
      and of various sex, using microdissection method. Characteristic cases were
      photographed. RESULTS: Sciatic nerve separated into the tibial and common
      peroneal nerve in popliteal fossa in 72.5% of the cases (bilaterally in the 66%
      of the cases). In the remainder of the cases the sciatic nerve division was high
      (27.5% of the cases) in the posteror femoral or in the gluteal region. Sciatic
      nerve left the pelvis through the infrapiriform foramen in 192 lower extremities
      (96% of the cases), while in 8 lower extremities (4% of the cases) the variable
      relations between sciatic nerve and piriform muscle were detected. The common
      peroneal nerve penetrated the piriform muscle and left the pelvis in 5 lower
      extremities (2.5% of the cases) and the tibial nerve in those cases left the
      pelvis through the infrapiriform foramen. In 3 lower extremities (1.5% of the
      cases) common peroneal nerve left the pelvis through suprapiriform, and the
      tibial nerve through the infrapiriform foramen. The high terminal division of
      sciatic nerve (detected in 1/3 of the cases), must be kept in mind during the
      performing of popliteal block anesthesia. CONCLUSION: Although very rare,
      anatomical abnormalities of common peroneal nerve in regard to piriform muscle
      are still possible.

PMID- 15715350
TI  - [Nutritional problems among elderly].

PMID- 15715351
TI  - [Angiogenesis in the central nervous system: a role of vascular endothelial
      growth factor].

PMID- 15715352
TI  - [War, traffic and iatrogenic injuries of D3 duodenal segment].
AB  - BACKGROUND: Injuries of the duodenum at the level of aortomesenteric clamp
      (segment D3) are with a high incidence of death due to the development of fistula
      and peritonitis. In three successfully managed cases, we applied the biliary
      surgery method. CASE REPORTS: All three cases were with the injuries of D3
      duodenal segment. The first patient suffered from the blast perforation of
      duodenum at the level of the aortomesenteric clamp which occurred at the 7th day
      after the injury. The second patient suffered from the duodenal injury caused in
      a traffic accident. The third patient suffered from an iatrogenic injury at the
      beginning of D3 duodenal segment inflicted during ureterolithotomy. The described
      surgical procedure included basically the suture to narrow the site of the
      injury, then lateroterminal anastomosis with the Roux-en-Y jejunal flexure and,
      finally, the placement of a silicone prosthesis starting from the duodenum
      through the site of injury and the Roux-en-Y out. Octreotide and the total
      parenteral nutrition were administered to the patients postoperatively.
      CONCLUSION: The use of the releasing silicone prosthesis in all three patients
      provided the repair of the site of the injury with anastomosed Reux-en-Y jejunum.

PMID- 15715353
TI  - [Ischemic preconditioning].
AB  - BACKGROUND: Ischemic preconditioning is a phenomenon during which myocardium,
      subjected to brief episodes of ischemia followed by reperfusion, tolerates better
      the subsequent, more prolonged episode of this ischemia, thus reducing the
      infarction size substantially. CASE REPORT: Two patients with acute left anterior
      descendent artery occlusion received fibrinolytic therapy (alteplase) within 6
      hours of the onset of chest pain, but developed myocardial infarctions of
      different sizes. The first patient, without the history of preinfarction angina,
      developed large anterior infarct, because there was no time either for ischemic
      preconditioning or for the coronary collateral vessels development. In the second
      patient, with 4-day history of preinfarction angina, the more favorable outcome
      was seen he developed smaller apical necrosis, with the great degree of
      myocardial viability in the infarct-related area. CONCLUSION: Ischemic
      preconditioning in patients with acute myocardal infarction results in the
      reduction of mortality, infarction size, as well as in the frequency of malignant
      arrhythmias.

PMID- 15715354
TI  - [Agranulocytosis induced by metamizole and its management with granulocyte growth
      factor].
AB  - Drug-induced agranulocytosis was defined as a severe selective neutropenia caused
      by an unexpected drug reaction. Metamizole was the most common nonopioid
      analgesic drug associated with agranulocytosis. It was also associated with
      combined blood dyscrasias and other severe immunologic disorders. The risk of
      agranulocytosis by metamizole seemed to be considerably higher than estimated
      formerly. Modern management with broad-spectrum antibiotics and haematopoietic
      growth factors reduced the mortality in those patients. Two cases of
      agranulocytosis caused by metamizole were reported.

PMID- 15715355
TI  - Cognition, behavior and the frontal lobes.

PMID- 15715356
TI  - Statistical audit of original research articles in International Psychogeriatrics
      for the year 2003.
AB  - BACKGROUND: At the request of the Editor of International Psychogeriatrics, a
      statistical audit of all papers published in the journal during 2003 was
      undertaken by the statistical advisor to International Psychogeriatrics. METHOD:
      Only research papers using inferential statistical techniques were assessed and
      only the statistical elements of these papers were evaluated. The following
      issues were addressed: did the authors report a power calculation or address
      power issues? Did the authors report an appropriate effect size indicator? When
      multiple univariate statistical tests were used was a correction for type 1 error
      employed? Did authors demonstrate the adequacy of the data analyzed for the
      statistical tests employed? Were sufficient details reported to enable an
      evaluation of the statistical analyses and reported results? RESULTS: Twenty
      papers published during 2003 were suitable for analysis. None addressed power
      issues. About half reported an effect size indicator and about half adjusted the
      statistical analysis for the effects of multiple univariate statistical
      comparisons. Few demonstrated the adequacy of the data being analyzed and few
      provided sufficient detail to evaluate the statistical analyses and reported
      results. Most papers used the right statistic in the right way. CONCLUSION: The
      statistical quality of articles published in International Psychogeriatrics could
      be improved by attention to a few relatively fundamental issues.

PMID- 15715357
TI  - Instruments to assess decision-making capacity: an overview.
AB  - OBJECTIVE: The main objective of this article is to evaluate and describe
      instruments for assessing decision-making capacity in psychiatry and
      psychogeriatrics, and to evaluate them for use in daily practice. METHODS: The
      instruments were selected in Medline articles. We focus on the relationship
      between these instruments and the concept of competence, represented in the
      following elements: context in which an instrument is developed, disclosure of
      information, standards to assess decision-making capacity, the scale or threshold
      model, and validity and reliability. RESULTS: The developmental context
      influences how information is provided and standards defined. Although it is not
      clear how decision-making capacity relates to competency judgments, most
      instruments provide good reliability. CONCLUSIONS: Comparison of the different
      instruments opens directions for future research. Although instruments can never
      replace a physician's judgment, they may provide a clear starting point for a
      discussion on competence. In daily practice assessments, attention should be
      given to information disclosure, the influence of our own normative values in
      evaluating standards of decision-making capacity, and the relation between
      decision-making capacity and competence.

PMID- 15715358
TI  - Disclosing the diagnosis of dementia: the performance of Flemish general
      practitioners.
AB  - BACKGROUND: This issue of whether or not, how and when patients should be told of
      the diagnosis of dementia remains a matter for discussion. Recent data confirm
      that the patient is told of the diagnosis in only 40 to 55% of cases. We
      therefore studied the performance of Flemish general practitioners (GPs) in this
      area. METHOD: A postal questionnaire, based on that prepared by Johnson et al.,
      was sent to a random sample of 1000 Flemish GPs, out of a total of 7000. RESULTS:
      A total of 647 answers were returned, of which 521 were eligible for analysis
      (response rate 60%). Thirty-six percent of these 521 GPs always or usually
      disclose the diagnosis, while 37% provide information about the prognosis. Most
      doctors (75%) see benefits in disclosure, particularly as regards planning care,
      providing treatment and encouraging a good doctor-patient relationship. Only 61%
      of respondents present an appropriate differential diagnosis. DISCUSSION: The
      results obtained from the Flemish GPs are similar to those of other known
      studies. A detailed analysis of the reasons for and the benefits of disclosing
      the diagnosis reveal a less reluctant attitude than could be inferred from the
      rough data. GPs pay a great deal of attention to the patient's feelings,
      experiences and ability to cope and to the proper timing of their information.
      However, intensive educational projects have to be set up in order to stimulate a
      more etiologically-oriented diagnosis and to improve the quality of the process
      of disclosing the diagnosis of dementia.

PMID- 15715359
TI  - "The good life" for demented persons living in nursing homes.
AB  - BACKGROUND: This study investigated which concepts regarding "the good life" are
      used in mission statements of nursing homes providing care for demented patients.
      METHOD: All 317 Dutch nursing homes caring for demented patients were asked to
      participate; of these, 69% responded. Their mission statements were qualitatively
      analyzed on content. Whether different types of nursing home differed
      significantly in the content of their mission statements was investigated by
      means of chi2 analyses. RESULTS: Six main concepts were found that are considered
      important for a good life: 1) autonomy and freedom, 2) individuality and
      lifestyle, 3) relationships and social networks, 4) warmth and safety and
      familiarity, 5) developing capacities and giving meaning to life and 6)
      subjective experience and feelings of well-being. It was found that mission
      statements specifically developed for demented patients attach less importance to
      the concepts 1) autonomy and freedom and 2) individuality and lifestyle, than
      mission statements which are also aimed at non-demented residents. Most mission
      statements turned out to be highly eclectic in content. CONCLUSION: Nursing homes
      with a separate statement for demented residents seem to acknowledge the special
      position of demented residents and the tension between dementia and the ideal of
      autonomy. Although the eclecticism found in mission statements is understandable,
      a coherent view on the good life for demented residents should aim for a sound
      internal structure, and make choices between values. Only then can mission
      statements provide real guidance for everyday care.

PMID- 15715361
TI  - Prevalence and appropriateness of psychotropic drug use in old age: results from
      the Berlin Aging Study (BASE).
AB  - BACKGROUND: The aim of this epidemiological study is to examine the prevalence
      and correlates of psychotropic drug use in the very old and to evaluate the
      appropriateness of psychotropic drug use in very old age. METHODS: Data from the
      Berlin Aging Study (BASE), a multidisciplinary study of an age- and gender
      stratified, randomly selected sample of elderly people living in Berlin are
      presented. Over-sampling, especially very old men, allows for powerful analyses
      of this population. All participants went through extensive psychiatric and
      somatic examinations. Medication intake was assessed by different data sources
      (interviewing patients and their family physicians, drug inspection at home).
      Results were brought together in a consensus-conference and research physicians
      gave operationalized ratings of medication appropriateness. RESULTS: The
      prevalence of elderly people who were taking at least one psychotropic medication
      within the 14 days immediately preceding investigation was 29.8%. Of these
      medications, 68.4% had been taken for longer than one year. There was no effect
      of age or gender on the scope of psychotropic drug use. Benzodiazepines were
      taken by 19.8% of the elderly. Antidepressants, neuroleptics and anti-dementia
      drugs were taken by about 3-4% each. People taking psychotropic drugs had
      significantly higher levels of psychiatric morbidity, as measured by syndromes
      and specified diagnoses. Psychotropic drugs were significantly less often judged
      to be indicated than somatic medications. This is mostly due to benzodiazepines.
      CONCLUSIONS: Psychotropic drug use is common in old age, but there is no
      additional increase in usage beyond the age of 70. Intake of psychotropics is
      mostly oriented at symptoms or syndromes, which explains why benzodiazepines are
      still the most commonly prescribed psychotropics.

PMID- 15715360
TI  - Behavioral and psychological symptoms of dementia in developing countries.
AB  - BACKGROUND: Little is known about the prevalence of, or associations with
      behavioral and psychological symptoms of dementia (BPSD) in developing countries.
      METHODS: Individuals diagnosed as having dementia according to DSM-IV criteria
      (mild and moderate cases as defined by the Clinical Dementia Rating scale only),
      together with their main caregiver, were recruited from 21 centers in 17
      developing countries. People with dementia were directly assessed with the
      Community Screening Interview for Dementia and the Geriatric Mental State
      Schedule (GMS); GMS data were processed by the AGECAT computer program to yield
      diagnostic information on 8 psychiatric syndromes. Caregivers answered direct
      questions about behavioral symptoms of dementia (BSD) and completed the Zarit
      Burden Inventory. RESULTS: At least one BSD was reported in 70.9% of the 555
      participants. At least one case-level AGECAT psychiatric syndrome (not including
      the organic syndrome) was exhibited by 49.5% of people with dementia. Depression
      syndromes (43.8%) were most common followed by anxiety neurosis (14.2%) and
      schizophreniform/paranoid psychosis (10.9%). Caregivers were more likely to
      report BSD in people with dementia who were married, younger and better educated.
      More advanced dementia, poorer functioning and the presence of depression or
      anxiety were each associated with BSD. BSD, and psychiatric syndromes (anxiety
      neurosis and schizophreniform/paranoid psychosis) predicted caregiver strain
      after controlling for cognitive impairment. BPSD are poorly understood, leading
      to shame and blame. CONCLUSIONS: BPSD are common among people with dementia in
      developing countries, though we found marked regional variations. Representative
      population studies are needed to clarify prevalence and impact, but our research
      suggests considerable unmet need, with much scope for intervention. Raising
      awareness of the problem should be the first step.

PMID- 15715362
TI  - Is apathy in late-life depressive illness related to age-at-onset, cognitive
      function or vascular risk?
AB  - BACKGROUND: Apathy has been shown to be an important feature of degenerative,
      vascular or traumatic brain disorder. Its presence is associated with high
      depression scores, higher age, low performance on frontal tasks, and more severe
      deep white matter hyperintensities. In late-life depression, lack of interest or
      motivation are often more prominent than depressed mood, especially in the late
      onset type. It was hypothesized that in a heterogeneous sample of elderly
      depressed patients, apathy is associated with late-onset type of depression,
      cognitive dysfunction or vascular risk factors. METHOD: The Apathy Evaluation
      Scale (AES) was administered to twenty-nine elderly (> or = 60 years) inpatients
      with a DSM-IV major depression or dysthymic disorder. The severity of the
      depression was measured with the Montgomery-Asberg Depression Rating Scale
      (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The
      presence of vascular risk factors was traced in the patient's medical records.
      RESULTS: Apathy was found in 86% of the patients. The AES-score was correlated
      with the negative symptom score, but not with total MADRS or MMSE-score. No
      difference in AES-score between early-onset depressed (n = 16) and late-onset
      depressed (n = 13) patients was found, and between patients with or without
      vascular risk. CONCLUSION: Apathy is a main feature of moderate to severe
      depressive illness in elderly patients and related to the negative symptoms of
      the disorder. Further studies should include less severely depressed patients and
      investigate the relation between depression severity and apathy.

PMID- 15715363
TI  - P300 event-related potential in late-onset schizophrenia.

PMID- 15715364
TI  - Charles-Bonnet syndrome and musical hallucination.

PMID- 15715365
TI  - Hospital admissions for acute onset of behavioral symptoms in demented patients:
      what do they want to say?

PMID- 15715366
TI  - Cerebrovascular events after treatment of dementia patients with risperidone.

PMID- 15715367
TI  - [Liver fibrosis: pathophysiology, diagnosis and treatment].
AB  - The extracellular matrix deposition in the liver parenchyma is a major component
      of cirrhosis. A great deal of knowledge has been gathered in the past two decades
      regarding the regulation and dynamics of fibrogenesis, and based on these
      advances, a review is delivered on the pathophysiology, diagnosis and therapy of
      liver fibrosis. The key event in fibrogenesis is the activation of hepatic
      stellate cells, and in its mechanism, inflammation, oxidative stress, steatosis,
      cytokines, growth factors, enzymes and enzyme inhibitors play a pivotal role. The
      phenotypic response of activated stellate cells comprises proliferation,
      fibrogenesis, contractility, loss of vitamin A and matrix degradation. In the
      diagnosis of liver fibrosis, besides liver biopsy--as "golden standard"--recently
      non-invasive methods, such as imaging techniques, and mainly serum fibrosis
      markers and indices have widely been studied. Experimental and clinical data have
      proved the reversibility of fibrosis, and suggested that an effective
      antifibrotic treatment in the future may serve even for the prevention of
      cirrhosis.

PMID- 15715368
TI  - [Effective treatment strategy in elderly breast cancer patients].
AB  - INTRODUCTION: High frequency of cancer in older people and the improvements in
      life expectancy do not allow older age to be a barrier to treatment. The age is
      one of the risk factors for breast cancer development, one third of all cases
      occur in women older than 70 years. AIM: To provide an overview of the available
      information on the main issues in the field of surgery, radiotherapy and medical
      approaches to the treatment of breast cancer in the elderly. METHOD: The author
      discusses the treatment of breast cancer in the elderly, based on the data of
      literature. RESULTS: The assessment of any patient is the first step in the
      treatment process, performance status is more important than age. In older women
      a correct evaluation includes not only the basic medical history and the cancer
      staging, but also a detailed assessment of health and environment that may
      interfere with the therapeutic approach of the patient. Age is not a limitation
      for surgery, without any comorbidity it is safe, and operative mortality is low.
      The body self-image is important for most old women, they also wish to keep their
      breasts, so a conservative surgery and adjuvant radiotherapy should be offered to
      all, as long as the stage permits it. The selection of patients who are
      candidates for axillary dissection is based on selective lymph sentinel node
      technique which provides an optimal nodal staging with a minimal morbidity. The
      results of radiotherapy are as good as in younger patients, elderly women
      tolerate radiotherapy well. The inability to travel to the radiation facility is
      often the reason for omitting the radiation treatment and to choose a modified
      mastectomy. A promising alternative to the standard radiation treatment is the
      concept of intraoperative radiotherapy. Breast cancer in the elderly women is
      more likely to be well differentiated tumour, containing oestrogen and
      progesterone receptors. Based on these favourable prognostic factors, endocrine
      therapy is the standard treatment in adjuvant and metastatic setting for older
      women. When all hormonal options have been exhausted, elderly women should be
      treated with chemotherapy. Older patients often use several drugs concomitantly,
      and this polypharmacy may lead to possible clinically significant changes in the
      cytotoxic agent pharmacology. Supportive care can improve compliance of patients
      to chemotherapy. The introduction of oral and weekly applied cytotoxic treatments
      will allow a broader spectrum of patients to benefit from chemotherapy,
      particularly those with a poorer performance status. CONCLUSIONS: The use of a
      multidimensional geriatric evaluation permits a better selection of the best and
      individualized therapeutic decision for each patient. The growing number of
      treatment options in the elderly breast cancer patients will lead to an increase
      in survival and contribute to an improvement in their quality of life.

PMID- 15715369
TI  - [Correlation of B-type natriuretic peptide (NT-proBNP) levels and conventional
      and tissue Doppler echocardiographic parameters of left ventricular diastolic
      function in patients with hypertrophic cardiomyopathy].
AB  - INTRODUCTION: Preload-independent pulsed tissue Doppler echocardiography (TDI)
      and conventional pulsed Doppler echocardiography were used to assess the global
      left ventricular diastolic function in patients with hypertrophic cardiomyopathy
      (HCM). Levels of B-type natriuretic peptide (BNP) could be elevated in patients
      with isolated left ventricular diastolic dysfunction. AIM: The study was to
      investigate the correlation between BNP levels and the parameters measured by
      conventional echocardiography and TDI in patients with HCM. PATIENTS: 32
      consecutive patients with HCM (21 male, 11 female, mean age 47 +/- 14 years) were
      studied. Inclusion criteria were: normal sinus rhythm; ejection fraction > or =
      50%; absence of moderate to severe mitral regurgitation or prosthetic mitral
      valve. METHODS: In addition to the conventional transmitral flow patterns (E, A,
      E/A, DT, IVRT) myocardial early (Ea) and late diastolic (Aa) velocities were
      measured at the lateral and septal border of the mitral annulus by ATL HDI 5000
      ultrasound system. Ea/Aa and E/Ea ratios were calculated. NT-proBNP levels were
      measured by Roche-Elecsys test (immunoassay). Because the distribution of BNP
      values did not appear to be normal, the values were transformed into a natural
      logarithm (InBNP). RESULTS: Mean BNP level was 543 +/- 845 pg/ml. BNP levels
      negatively correlated with lateral Aa values (r = -0.59, p < 0.001). No
      significant relationship was observed between BNP levels and other
      echocardiographic parameters. By stepwise multiple linear regression analysis the
      only significant predictor of InBNP was lateral Aa value, too (r = -0.467, p <
      0.05). CONCLUSION: Significant correlation was found between BNP levels and a
      single TDI parameter characterizing left atrial systolic function, but there was
      no significant correlation between BNP levels and global left ventricular
      diastolic function characterized by either conventional echocardiographic or TDI
      parameters.

PMID- 15715370
TI  - [Dysmenorrhea in adolescent girls].
AB  - INTRODUCTION: Dysmenorrhea is highly prevalent during adolescence but the
      incidence of this disease is very often underestimated. Depending on different
      measurement methods 20-90% of adolescent girls report dysmenorrhea. OBJECTIVES:
      This study examined the prevalence of dysmenorrhea among high-school female
      adolescent students in Eastern-Hungary. Early diagnosis and treatment of the
      possible pathological background is very important to prevent long term
      consequences. RESULTS: 2337 girls were interviewed in this study about their
      menstrual cycle. The overall prevalence of dysmenorrhea in this population was
      79.2%. Altogether 67.0% described their pain and cramp as severe. 61.2% of the
      girls use some kind of medication due to dysmenorrhea. Despite these data only
      1.2% of them had previous medical counseling because of their complains.
      CONCLUSIONS: It is important to screen female adolescents for dysmenorrhea and
      provide them with information on the disease and possible treatment options.
      Follow up of these adolescents is mandatory especially in cases not responding to
      standard medical treatment.

PMID- 15715371
TI  - [Case of a young woman successfully operated on for acute pulmonary embolism and
      right ventricular thrombus after urogenital infection].
AB  - The authors report a case of a 22-year-old women operated on for pulmonary
      embolism with success. The venous embolism developed in two phases one week
      apart. The first clinical sign was a dyspnea of abrupt onset limiting physical
      activity even after a mild exertion. However, relevant diagnostic tests were
      performed after one week when the patient fainted, her dyspnea worsened. The
      results of ECG, echocardiography and pulmonary perfusion scintigraphy indicated
      the presence of a thrombus residing in the right ventricle and the embolism of
      the right pulmonary artery. Chest CT and pneumo-angiography findings show the
      embolus completely blocking the main right branch of the pulmonary artery and
      partially blocking the left lower lobe artery. On the basis of their experiences
      published earlier the patient was brought to a stable cardio-respiratory state
      prior to surgery. Both the adherent right ventricular thrombus and the fresh
      embolus residing in the right branch of the pulmonary artery were removed under
      the protection of extracorporeal circulation. After the elapse of an event-free 6
      month postoperative period the patient continued to remain symptomless, while
      being on a long-term anticoagulant regimen. The long-term anticoncipient
      medication and the urogenital infection 3 months prior to surgery may have been
      involved in the etiology of the pulmonary embolism. The authors propose the
      implementation of an antithrombotic prophylaxis in young women after
      gynecological infections.

PMID- 15715375
TI  - Evidence-based approach for treatment planning options for the extensively
      damaged dentition.
AB  - Restoring the extensively damaged dentition has always been a difficult decision
      making process for the dental practitioner. Decisions to restore these teeth were
      primarily based on the fact that "fixed" teeth are typically better functionally
      than "removable" teeth and better esthetically than "no" teeth. Prior to dental
      implants, restoring missing teeth and extensively damaged teeth utilizing
      traditional therapy such as crown lengthening, root hemisection/amputation,
      endodontic therapy, apical surgery, post and cores and splinting were the options
      available to our patients. These teeth typically required the expertise of
      additional specialist, however their prognosis and success rates were typically
      guarded at best. Presently, dental implant success rates have been clearly
      identified and documented in the literature which now questions the survivability
      and success rates of the traditional mode of therapy for extensively damaged
      teeth. This paper will attempt to review the dental literature for various
      traditional modes of therapy for restoring the extensively damaged to provide a
      consensus of their survivability to help the practitioner to present options and
      prognosis for their patients.

PMID- 15715374
TI  - A case for absolute anchorage.
AB  - It would be an understatement to say that implant technology has changed the face
      of dentistry in the past 10 years or so. Both the surgical and restorative
      specialties have undergone dramatic transformation from treatment planning
      through all phases of rehabilitation. However, the same cannot necessarily be
      said for the specialty of orthodontics. Although it could be argued that implants
      have had an impact on the planning and setup of orthodontic cases (such as in
      congenitally missing teeth situations), the actual utilization of implants as an
      integral part of mechanotherapy has only begun to be realized. The ultimate
      extension of this application of using implants to enhance tooth movement would
      be to employ implants that are designed solely for the purpose of facilitating
      orthodontic therapy, with no intention to restore, but rather to explant such
      implants, after their purpose is fulfilled.

PMID- 15715376
TI  - Surgical and prosthetic concepts for predictable immediate loading of oral
      implants.
AB  - Immediate loading of oral implants is an established concept for lower jaw
      restoration using four intraforaminal implants splinted together with a bar.
      There is a lot of misunderstanding in the literature and not exact definition of
      the term "immediate loading." Moreover, the number of implants to restore
      edentulous jaws is relatively high to compensate for the loading forces and
      dependent on the bone quality and quantity. This report presents the different
      surgical and prosthetic concepts for immediate loading to get long-term success
      in the upper and lower jaw. When the primary stability is adequate, only six
      implants may be loaded immediately after surgery, if the implants are splinted
      using a provisional fixed restoration. Using a number of six primary stable
      implants, it is possible to restore edentulous jaws independent on the clinical
      situation. This concept may be used successfully in the posterior part of the
      mandible when three implants are splinted with provisional crowns and loaded
      immediately. The biomechanical aspects, the implant design and surface seem to be
      of great importance for the long-term success in compromised and advanced
      surgical cases. In conclusion, immediate loading of oral implants may be
      successful if a primary stability as well as immobilization (splinting)
      immediately after surgery are taken care.

PMID- 15715377
TI  - Implant designs for the spectrum of esthetic and functional requirements.
AB  - In recent years, attention has shifted from merely achieving successful
      osseointegration of dental implants to achieving proper esthetics that mimic
      natural dentition. Original implant designs were primarily developed for the
      treatment of fully edentulous patients where esthetics was not a major objective
      of the therapeutic outcome. During the initial years of the development of
      osseointegrated implants, greater emphasis was placed on achieving successful
      osseointegration. As the number of patients undergoing implant therapy, as well
      as the number of clinical indications for dental implants, is rapidly expanding,
      the therapeutic armamentarium also has to expand. The most important requirement
      for achieving predictable esthetic results is careful consideration of the
      biology of the interaction between the implant-prosthesis complex with the
      implant site. Only those implant-supported restorations that achieve harmony with
      the surrounding hard and soft tissues can be expected to have an optimal esthetic
      outcome will endure.

PMID- 15715378
TI  - Implant site development: clinical realities of today and the prospects of tissue
      engineering.
AB  - The success of dental implants depends on their placement in bone of adequate
      density and volume in order to achieve primary stability. Optimal esthetics of
      implants requires their placement in a position approximating that of the natural
      teeth they replace. However, there is generally at least some degree of atrophy
      in the sites where implants are to be placed. This atrophy may occur either
      before or after tooth extraction. Following extraction of teeth, there is
      commonly alveolar ridge resorption in horizontal and vertical dimensions.
      Alternatively, some of the oral hard and soft tissues may be destroyed by
      pathologic conditions such as periodontitis, endodontic infections, or trauma.
      All of these conditions may potentially compromise the final esthetics and
      function of implant-supported restorations. During the initial years of the
      development of the osseointegration protocol, implants were placed with little or
      no modification of implant sites. Though osseointegration was successfully
      achieved, esthetic outcome was not a primary objective of therapy at that time. A
      gradual paradigm shift has occurred in implant dentistry from merely achieving
      successful osseointegration to achieving final restorative outcomes that mimic
      natural dentition and their surrounding oral tissues. These objectives have been
      materialized by advancements in surgical techniques, as well as availability of
      biomaterials to enable predictable regeneration of oral hard and soft tissues.
      The objective of the present review is to briefly discuss some of the techniques
      that are currently available for implant site development.

PMID- 15715379
TI  - Minimally invasive surgery: an alternative approach for periodontal and implant
      reconstruction.
AB  - Minimally invasive surgery is defined as a procedure involving a smaller access
      opening and less-extensive surgical manipulation of the tissues that surround the
      target structure. It represents a rapidly advancing and expanding therapeutic
      modality in medicine and dentistry. Minimally invasive surgery has been touted as
      one of the major advances in medicine of the past two to three decades. The
      revolution in this field has been made possible by technological advances in
      imaging, instrumentation, and robotics. These advances have been driven in part
      by patient demand. Today's patients lead a busy and active lifestyle, and
      prolonged periods of convalescence are not acceptable for many. Therefore, the
      advent of minimally invasive surgery has promoted increased patient acceptance,
      which result from decreased morbidity associated with the minimally invasive
      surgery approaches.

PMID- 15715380
TI  - Beyond the big (C).

PMID- 15715381
TI  - Avoiding another Vioxx.

PMID- 15715382
TI  - Hungry for dino meat.

PMID- 15715383
TI  - Punctuated disequilibrium.

PMID- 15715385
TI  - String revival.

PMID- 15715384
TI  - Into the abyss.

PMID- 15715386
TI  - More bits in pits.

PMID- 15715388
TI  - Abducted!

PMID- 15715387
TI  - Melting at the top.

PMID- 15715389
TI  - Performance without anxiety.

PMID- 15715391
TI  - Atom chips.

PMID- 15715390
TI  - An endangered species in the stomach.

PMID- 15715392
TI  - The littlest human.

PMID- 15715393
TI  - Seeking better Web searches.

PMID- 15715394
TI  - Making memories stick.

PMID- 15715395
TI  - Nanotubes in the clean room.

PMID- 15715397
TI  - Noise-canceling headphones. Reducing a roar.

PMID- 15715396
TI  - The new college try.

PMID- 15715398
TI  - Every breath you take.

PMID- 15715400
TI  - How are the abbreviations of the periodic table determined?

PMID- 15715399
TI  - Why do bags form below our eyes?

PMID- 15715401
TI  - [Expression of CD30 in nasal mucosa of patients with allergic rhinitis].
AB  - OBJECTIVE: To study the role of CD30 in the pathogenesis of allergic rhinitis.
      METHOD: The specimens of thirty-one patients with allergic rhinitis and twenty
      six control subjects were studied by immunohistochemical method to detect CD30
      cell. A mean numbers of positive cells per high field (10 x 40) were counted. All
      data were analyzed with t-test. RESULT: The number of CD30+ cells in the nasal
      mucosa of patients with allergic rhinitis was significantly more than that in the
      controls (P < 0.05). CONCLUSION: This study suggests a T-helper 2-dominated
      mucosal reaction in the allergic rhinitis compared to the nonallergic groups,and
      the expression level of CD30 can reflect the T-helper 2-dominated mucosal
      reaction.

PMID- 15715402
TI  - [Study on the relationship of airborne sensitization fungus and anaphylactic
      rhinitis in Wuhan].
AB  - OBJECTIVE: The aim of our studies is to explore the relation between superior
      sensitizing fungus and anaphylactic rhinitis, for directing the prevention,
      diagnosis and treatment of the disease. METHOD: Three hundred and ninety-two
      persons were treated by allergen skin test. Using 15 main sensitizing fungus, 90
      anaphylactic rhinitis were examined. The serum level of IgE were examined, too.
      RESULT: In the allergen skin testing 239 cases (60.97%) were positive, the
      positive rate was higher than that in contrast group (t = 5.47, P < 0.01). The
      main fungus allergen were Rhizopus nigricans, Cuvularia and Altevnaria, the value
      of IgE in patients group was higher than that in control group (t = 5.47, P <
      0.01). CONCLUSION: It proves that airborne sensitizing fungus are important
      causes of anaphylactic rhinitis.

PMID- 15715403
TI  - [Effects of intranasal cortocosteroidson on the expression of Aquaporin-5 in
      human nasal polyps].
AB  - OBJECTIVE: To observe the effects of intranasal Fluticasone propionate on the
      expression of Aquaporin-5 in nasal polyps and explore the role of AQP-5 in the
      formation of nasal polyps. METHOD: Twenty cases of nasal polyps were selected.
      Fluticasone propionate were intranasally used in 10 cases of nasal polyps for 7
      10 days before operation. The others, treated with nothing, were used as control.
      Twenty samples nasal polyps were obtained and studied with immunochemistric
      technique. RESULT: The expression of AQP-5 positive cells in the blood vessel
      endothelium was statistically significantly redueced in the Fluticasone
      propionate-using group compared with the control group (P < 0.05). The difference
      of AQP-5 positive cells in mucosal epithelial and glandular epithelium was not
      statistically significant between the Fluticasone propionate-using group and the
      control group. CONCLUSION: (1) AQP-5 might be a vital factor for the formation
      edema of nasal polyps. (2) The effects of Fluticasone propionate on nasal polyps
      may be related to changing the expression of AQP-5 to a degree. (3) The full
      exploration of regulation and control of Aquaporions can contribute to evaluate
      the pathogenesis of nasal polyps.

PMID- 15715404
TI  - [Expression of MUC5AC in human nasal polyp and inferior turbinate epithelium].
AB  - OBJECTIVE: To examine the expression of MUC5AC in human nasal polyp and inferior
      turbinate epithelium, to evaluate the relationship between MUC5AC and the
      increased mucous secretions in polyps and chronic hypertrophy rhinitis. METHOD:
      With immunohistochemistry ABC and HE dyeing, twenty-seven polyps, nineteen
      chronic hypertrophy rhinitis and eleven normal inferior turbinates epithelium
      were applied to this study. RESULT: The number of MUC5AC+ cells in nasal polyps
      and chronic hypertrophy rhinitis was significantly bigger than that in normal
      inferior turbinates (P < 0.05), and the MUC5AC+ cells were mainly concentrate on
      the goblet cells. CONCLUSION: MUC5AC is highly expressed in epithelium of human
      polyps and chronic hypertrophy rhinitis inferior turbinates, and MUC5AC takes
      part in increasing secretion in polyps and chronic hypertrophy rhinitis.

PMID- 15715405
TI  - [Clinical analysis on 18 cases of primary nasal cavity and sinuses T/NK
      lymphomas].
AB  - OBJECTIVE: To investigate the clinical characteristics and treatment effect of
      primary sinonasal T/NK lymphomas. METHOD: Eighteen cases of primary sinonasal
      T/NK lymphomas were reviewed retrospectively. The clinical behavior, clinical
      diagnostic characteristics and prognosis were studied. RESULT: The clinical
      symptoms of these patients included nasal obstruction, epistaxis, nasal
      discharge, intumescence, ulcer and fever so on. Clinical diagnosis was easy to be
      misdiagnosed. The prognosis of patients that higher stage and higher malignant
      were bad. CONCLUSION: Sinonasal T/NK lymphomas are a distinct clinicopathological
      category and the clinical symptoms are nonspecificness. We should pay attention
      to distinction and avoiding misdiagnosis. The prognosis is relative to
      pathological category and clinical stage.

PMID- 15715406
TI  - [Analysis of clinical manifestations in nasociliary neuralgia].
AB  - OBJECTIVE: To explore the clinical character of nasociliary neuralgia and improve
      the level of diagnosis and treatment. METHOD: Forty-three cases with nasociliary
      neuralgia were diagnosed and treated in our hospital. The clinical data were
      analyzed retrospectively. RESULT: It was easy to be misdiagnosed for nasociliary
      neuralgia,the rate of misdiagnosis was 69.8% (30/43). Performing the resection of
      upper nasal septum deviation, partial middle turbinetectkomy or/and folded, 43
      cases were followed up from 6 to 24 months,the cural rate and the improve rate
      were 95.3% and 4.7% respectively, with the total effective rate 100.0%.
      CONCLUSION: Most patients with nasociliary neuralgia are middle-aged women. It is
      similar to ethmoid sinusitis and frontal sinusitis in headache, but no
      suppurative rhinorrhea. Careful examination of nasal cavity and CT scan in sinus
      play an important role in avoiding misdiagnosis. The corrective surgery of middle
      turbinate and nasal septum are effective treatment and the complication of
      dysosmia can be avoided.

PMID- 15715407
TI  - [Reconstruction of tissue defects in external nose].
AB  - OBJECTIVE: To discuss and sum up the methods and experience of aesthetic
      reconstruction of tissue defects in external nose. METHOD: By respective repair
      based on aesthetic subunits principle of the nose proposed by Yotsuyanagi et al,
      47 tissue defects in external nose were reconstructed using random flap of
      nasolabial groove, local rhomboid flap, the insular skin flap of forehead,the
      insular skin flap of nasolabial groove with retrograde facial artery and forearm
      flap with pedicle etc. RESULT: Satisfactory resconstructive effects were obtained
      in all cases. CONCLUSION: Good aesthetic result can be achieved using local flaps
      or forearm flap with pedicle.

PMID- 15715408
TI  - [Expression and significance of PTEN in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the expression of tumor suppressor gene PTEN in
      nasopharyngeal carcinomas and the relationship between PTEN and the progression
      of nasopharyngeal cancer. METHOD: The SABC immunohistochemistry method was
      employed to detect the expression of PTEN in paraffin-embedded nasopharyngeal
      carcinoma tissues. The relationship between the geneexpression and
      clinicopathological features was analyzed. RESULT: Loss of PTEN expression in
      normal cases (13.3%) was lower than that in nasopharyngeal carcinoma cases
      (47.8%). Of nasopharyngeal cancer cases, loss of PTEN expression in squama cell
      nasopharyngeal (58.1%) was higher than that in others tissue type (30.8%); loss
      of PTEN expression in squama cell nasopharyngeal had correlation with
      pathological stage, which increased gradually from poorly differentiated to well
      differentiated squama cell nasopharyngeal; loss of PTEN expression of clinical
      III-IV stage (78.1%) was higher than that of clinical I-II stage (21.6%).
      CONCLUSION: It is presumed that PTEN gene deletion may be involved in
      carcinogenesis and progression of nasopharyngeal carcinoma, and relates to the
      tissue type, the pathological grade and clinical stage.

PMID- 15715409
TI  - [Clinical therapic procedure of obstinate epistaxis].
AB  - OBJECTIVE: To investigate the clinical treatment consideration and the therapic
      procedure. METHOD: We analyze the clinical data of 171 cases of obstinate
      epistaxis in recent years, mainly the pathogeny, treatment consideration and
      therapic procedure. RESULT: Were two steps were selected to the therapeutics
      according to different causations: step one, using the methods including nasal
      septum rectification, nasal cavity microwave cauterization, the curative ratio
      were 87.20%, 91.25% respectively; step two, using the methods including DSA
      (digital subtraction angiography), ligation of the external carotid artery,
      arteria ethmoidalis clipping, the curative ratio were 90%, 100%, 100%
      respectively. CONCLUSION: The thought of taking two steps methods to treat the
      obstinate epistaxis is very clear, and the curative effect is satisfactory as
      well.

PMID- 15715410
TI  - [Giant cell reparative granuloma of temporal bone and nasal bone].
AB  - OBJECTIVE: To discuss the etiology, typing, diagnosis, differential diagnosis and
      treatment of GCRG. ative granuloma (GCRG). METHOD: Two GCRG of temporal bone and
      nasal bone were analyzed. RESULT & CONCLUSION: GCRG is not a real neoplasm, it is
      very difficult to diagnose. Total surgical resection is an effective therapeutic
      method, the follow-up survey after surgery should be enhanced. For the recurrent
      cases, radiation therapy and anti-angiogenic therapy can be considered.

PMID- 15715411
TI  - [Expression of VEGF-C and VEGFR-3 in human laryngeal squamous cell carcinomas and
      cervical metastatic lymph node tissues].
AB  - OBJECTIVE: To study the gene expression of vascular endothelial growth factor C
      (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3) in laryngeal
      squamous carcinoma and their relation with clinic pathologic features. METHOD:
      VEGF-C and VEGFR-3 gene expression in 30 cases of normal laryngeal mucosa tissue
      (NLM), primary laryngeal carcinoma (PLC) and cervical lymph node (CLN) were
      examined by reverse transcription polymerase chain reaction (RT-PCR). RESULT: The
      gene expression of VEGF-C and VEGFR-3 are different among normal laryngeal mucosa
      tissue, primary laryngeal carcinoma and cervical lymph node in the same patient.
      In primary laryngeal carcinoma, expression of VEGF-C, VEGFR-3 were significantly
      higher in lymph node positive group than in lymph node negative group and
      associated with histological grade of differentiation; The gene expression of
      VEGF-C, VEGFR-3 were not associated with age, sex, site, T stage. CONCLUSION:
      VEGF-C, VEGFR-3 have prognostic significance in laryngeal carcinoma.

PMID- 15715412
TI  - [The clinical analysis of endoscopic repair of cerebrospinal fluid rhinorrhea].
AB  - OBJECTIVE: To evaluate the points for attention, repair material and the
      treatment of complications in repairing cerebrospinal fluid rhinorrhea. METHOD:
      Fifteen cases of cerebrospinal fluid rhinorrhea were repaired. One case was
      pituitary tumor involving radiotherapy, two cases were spontaneous, six were
      traumatic, six were traumatic,six were iatrogenic. RESULT: All cases were
      successfully repaired by endoscopy. The successful rate were 85.6%. Some cases
      were relapsed in different positions and some cases needed to be repaired more
      than two times even five times. CONCLUSION: Endoscopic repair of cerebrospinal
      fluid rhinorrhea is a very good method with the virtue of convenient, high
      successful rate, less complication and repeatability. The method is worth
      spreading.

PMID- 15715413
TI  - [The effect of the lesion in tympanic ostium on the disfunction of Eustachian
      tube in patients with chronic otitis media].
AB  - OBJECTIVE: To explore the relation of tympanic ostium of Eustachian tube and
      Eustachian tube dysfunction in chronic otitis media. METHOD: Tympanic ostium of
      Eustachian tube was observed by tele-otoscope and the active and passive function
      of Eustachian tube were detected in 44 case of chronic otitis media (include 45
      ears). RESULT: The lesion of tympanic ostium of Eustachian tube based on
      observation of tele-otoscope was divided into mild and serious alteration. The
      mild alteration revealed bony hyperplasia, mucosal swelling but tympanic ostium
      was open. The serious alteration revealed the serious mucosal swelling,
      granulation and tympanic ostium narrow. Seventeen out of 45 ears of chronic
      otitis media were normal tympanic ostium of Eustachian tube, whereas 18 ears and
      10 ears were mild and serious alteration respectively. In 10 ears with serious
      alteration of tympanic ostium, 9 ears revealed the obstruction of Eustachian
      tube. CONCLUSION: The bony hyperplasia, mucosal swelling and granulation in
      tympanic ostium are usual lesion in chronic otitis media. The narrow of tympanic
      ostium induced by serious mucosal swelling and granulation is one of causes
      resulting in tube disfunction.

PMID- 15715414
TI  - [The clinic manifestation of 86 cases with human immunodeficiency virus infection
      on pharynx and larynx].
AB  - OBJECTIVE: To understand and recognize the clinic manifestation of HIV infection
      on pharynx and larynx. METHOD: Eighty-six cases with HIV infection in Dodoma,
      Tanzania were briefly reviewed. According to the laboratory results, all patients
      received the treatments of antibiotics, antifungal agents and heteropathy or
      supporting treatment. RESULT: The follow-up was from 4 to 20 months. Fifty-nine
      cases improved after treatment while 24 cases didn't improved and 3 cases died.
      CONCLUSION: The otolaryngologist must be familiar with different diagnostic
      possibilities and therapeutic alternatives when patients present with throat
      complaints. Local infections were characterized by the recurrence and deferment.

PMID- 15715415
TI  - [Malignant transformation of a human oral squamous cell carcinoma cell strain OSC
      19 by EBV encoded small RNAs].
AB  - OBJECTIVE: To observe the growth characteristics of the EBERs-transfected OSC
      (oral squamous carcinoma)-19 cells, through generated overexpression of EBERs in
      OSC-19 cells. METHOD: EBERs fragment were amplified by PCR from EBV-positive NPC
      KT cell DNA. Using molecular biologic technique, we constructed the EBERs
      expressing plasmids, which contained, 4 or 10 tandem repeats of the EBERs. The
      OSC-19 cells were transfected with those plasmids, respectively. We demenstrated
      the overexpression of EBERs in EBERs-transfected OSC-19 cells by Northern Blot
      analysis, and compared the growth characteristics in culture and colony formation
      in soft agar of Hygr- and EBERs-transfected OSC-19 cells. RESULT: 10EBERs
      transfected OSC-19 cells lost cell-to-cell contacts and acquired long spindle
      shape morphology in culture and formed colonies in soft agar. However, parental
      and Hygr-transfected OSC-19 cells scarcely did. CONCLUSION: In this study, we
      established 10 EBERs-transfected OSC-19 cells, which overexpressing the EBERs and
      showed that it has a scattering activity in culture and a role in anchorage
      independent growth in soft agar. These results indicate that EBERs has a role of
      malignant transformation in OSC-19 cells. However, the 10 EBERs-transfected OSC
      19 cell provides a useful epithelial model for studying the function of EBERs.

PMID- 15715416
TI  - [The relationship between the fragment deletion of mtDNA in old rat and the
      sensitivity to aminoglycoside antibiotic induced deafness].
AB  - OBJECTIVE: To analyze the relationship between the fragnent deletion of
      mitochondrial DNA (mtDNA) of inner ear in rats and aminoglycoside antibiotic
      induced deafness (AAID), and to investigate the possible role of mtDNA deletion
      in the sensitivity to aminoglycoside antibiotic induced deafness in old rat.
      METHOD: Thirty wistar rats were divided into group A (old rat, > 24 months, n =
      15) and group B (young rat, 4 months, n = 15) according to the age. Kanamycin
      (KM) was intraperitoneally injected 500 mg/kg per day for 10 consecutive day in
      all rats. The threshold of the auditory brainstem response (ABR) was measured
      before and after the drug administrations. The inner ear tissue was harvested and
      the mtDNA was amplified to identify the 4834 bp deletion by PCR technique.
      RESULT: The elevation of the mean ABR thresholds in group A (42.08 +/- 8.19) dB
      peSPL was significantly higher than that in group B (12.71 +/- 4.42) dB peSPL (P
      < 0.01). In group A, 10 of the 15 rats demonstrate the mtDNA4834 deletion and the
      elevation of the mean ABR thresholds in the rats with mtDNA4834 deletion (45.00
      +/- 7.67) dB peSPL was significantly higher than that without so deletion (33.33
      +/- 4.08) dB peSPL (P < 0.01). However, mtDNA4834 deletion was negative in group
      B. CONCLUSION: Deletion of mtDNA of inner ear tissue in old rat is found. The
      mtDNA deletion may play an important role in the hypersensitivity to
      aminoglycoside antibiotic ototoxiciy in old rats.

PMID- 15715417
TI  - [The expression and significance of VIP and SP in the cochlea of rats].
AB  - OBJECTIVE: To investigate the expression of vasoactive intestinal peptide (VIP)
      and substance P (SP) in the cochlea of spontaneously hypertensive rat (SHR) and
      normal rat, and to evaluate the function of VIP and SP in the cochlea following
      the damage of hypertension. METHOD: The expression of VIP and SP in the cochlea
      of SHR was studied by immunohistochemical staining, and the mean optical density
      (OD) values of the positive fields were quantitatively examined by image analysis
      system. RESULT: The number of spiral ganglion cells at base turn in the
      hypertension group was significantly less than the normal (P < 0.01). VIP was
      expressed in the spiral ganglion cell plasm and stria vascularis of rats, so did
      SP. In spiral ganglion cell plasm the expression of VIP and SP had no significant
      difference between the two groups (P > 0.05); in stria vascularis the expression
      of VIP of the hypertension group was higher than the normal (P < 0.05). However,
      no significant difference in SP was found between the two groups. CONCLUSION: VIP
      not only contributes to regulate the cochlea microcirculation, but also acts as
      the neurotransmitter in the pathway of the auditory system. However, SP may be
      only a neurotransmitter in the pathway of the auditory system.

PMID- 15715418
TI  - Quantitative measurement of regional lung gas volume by synchrotron radiation
      computed tomography.
AB  - The aim of this study was to assess the feasibility of a novel respiration-gated
      spiral synchrotron radiation computed tomography (SRCT) technique for direct
      quantification of absolute regional lung volumes, using stable xenon (Xe) gas as
      an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic
      x-ray beams was used to visualize and directly quantify inhaled Xe concentrations
      and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume
      measurements were validated using a hollow Xe-filled phantom. Spiral images
      spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20%
      O2 gas mixture, in two anaesthetized and mechanically ventilated rabbits at
      baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung
      sections were obtained at functional residual capacity (FRC) and at end
      inspiration. 3D images showed large patchy filling defects in peripheral airways
      and alveoli following histamine provocation. Local specific lung compliance was
      calculated based on FRC/end-inspiration images in normal lung. This study
      demonstrates spiral SRCT as a new technique for direct determination of regional
      lung volume, offering possibilities for non-invasive investigation of regional
      lung function and mechanics, with a uniquely high spatial resolution. An example
      of non-uniform volume distribution in rabbit lung following histamine inhalation
      is presented.

PMID- 15715419
TI  - Image reconstruction in regions-of-interest from truncated projections in a
      reduced fan-beam scan.
AB  - In a reduced fan-beam scan, the scanned angular range is smaller than that in a
      short scan (i.e., a half-scan). In this work, we have developed a new algorithm,
      which is referred to as the backprojection-filtration (BPF) algorithm, for exact
      image reconstruction within ROIs from reduced-scan data containing truncations.
      Explicit conditions on data acquisition have also been derived for exact image
      reconstruction within an ROI. We have performed a preliminary quantitative study
      whose results demonstrated and verified the proposed fan-beam BPF algorithm and
      the derived conditions on data acquisition. The proposed BPF algorithm can have
      significant implications for clinical and animal CT imaging, therapy imaging,
      electron paramagnetic resonance imaging and other tomographic imaging because it
      allows for reconstruction from truncated data and for a potentially drastic
      reduction of radiation dose and/or of imaging time.

PMID- 15715420
TI  - Evaluation of high performance data acquisition boards for simultaneous sampling
      of fast signals from PET detectors.
AB  - Detectors used for positron emission tomography (PET) provide fast, randomly
      distributed signals that need to be digitized for further processing. One
      possibility is to sample the signals at the peak initiated by a trigger from a
      constant fraction discriminator (CFD). For PET detectors, simultaneous
      acquisition of many channels is often important. To develop and evaluate novel
      PET detectors, a flexible, relatively low cost and high performance laboratory
      data acquisition (DAQ) system is therefore required. The use of dedicated DAQ
      systems, such as a multi-channel analysers (MCAs) or continuous sampling boards
      at high rates, is expensive. This work evaluates the suitability of well-priced
      peripheral component interconnect (PCI)-based 8-channel DAQ boards (PD2-MFS-8
      2M/14 and PD2-MFS-8-500k/14, United Electronic Industries Inc., Canton, MA, USA)
      for signal acquisition from novel PET detectors. A software package was developed
      to access the board, measure basic board parameters, and to acquire, visualize,
      and analyse energy spectra and position profiles from block detectors. The
      performance tests showed that the boards input linearity is >99.2% and the
      standard deviation is <9 mV at 10 V for constant signals. Synchronous sampling of
      multiple channels and external synchronization of more boards are possible at
      rates up to 240 kHz per channel. Signals with rise times as fast as 130 ns (<2 V
      amplitude) can be acquired without slew rate effects. However, for signals with
      amplitudes of up to 5 V, a rise time slower than 250 ns is required. The measured
      energy resolution of a lutetium oxyorthosilicate (LSO)-photomultiplier tube (PMT)
      detector with a 22Na source was 14.9% (FWHM) at 511 keV and is slightly better
      than the result obtained with a high-end single channel MCA (8000A, Amptek, USA)
      using the same detector (16.8%). The crystals (1.2 x 1.2 x 12 mm3) within a 9 x 9
      LSO block detector could be clearly separated in an acquired position profile.
      Thus, these boards are well suited for data acquisition with novel detectors
      developed for nuclear imaging.

PMID- 15715422
TI  - A library based fitting method for visual reflectance spectroscopy of human skin.
AB  - The diffuse reflectance spectrum of human skin in the visible region (400-800 nm)
      contains information on the concentrations of chromophores such as melanin and
      haemoglobin. This information may be extracted by fitting the reflectance
      spectrum with an optical diffusion based analytical expression applied to a
      layered skin model. With the use of the analytical expression, it is assumed that
      light transport is dominated by scattering. For port wine stain (PWS) and highly
      pigmented human skin, however, this assumption may not be valid resulting in a
      potentially large error in visual reflectance spectroscopy (VRS). Monte Carlo
      based techniques can overcome this problem but are currently too computationally
      intensive to be combined with previously used fitting procedures. The fitting
      procedure presented herein is based on a library search which enables the use of
      accurate reflectance spectra based on forward Monte Carlo simulations or
      diffusion theory. This allows for accurate VRS to characterize chromophore
      concentrations in PWS and highly pigmented human skin. The method is demonstrated
      using both simulated and measured reflectance spectra. An additional advantage of
      the method is that the fitting procedure is very fast.

PMID- 15715421
TI  - Low resolution brain electromagnetic tomography in a realistic geometry head
      model: a simulation study.
AB  - It is of importance to localize neural sources from scalp recorded EEG. Low
      resolution brain electromagnetic tomography (LORETA) has received considerable
      attention for localizing brain electrical sources. However, most such efforts
      have used spherical head models in representing the head volume conductor.
      Investigation of the performance of LORETA in a realistic geometry head model, as
      compared with the spherical model, will provide useful information guiding
      interpretation of data obtained by using the spherical head model. The
      performance of LORETA was evaluated by means of computer simulations. The
      boundary element method was used to solve the forward problem. A three-shell
      realistic geometry (RG) head model was constructed from MRI scans of a human
      subject. Dipole source configurations of a single dipole located at different
      regions of the brain with varying depth were used to assess the performance of
      LORETA in different regions of the brain. A three-sphere head model was also used
      to approximate the RG head model, and similar simulations performed, and results
      compared with the RG-LORETA with reference to the locations of the simulated
      sources. Multisource localizations were discussed and examples given in the RG
      head model. Localization errors employing the spherical LORETA, with reference to
      the source locations within the realistic geometry head, were about 20-30 mm, for
      four brain regions evaluated: frontal, parietal, temporal and occipital regions.
      Localization errors employing the RG head model were about 10 mm over the same
      four brain regions. The present simulation results suggest that the use of the RG
      head model reduces the localization error of LORETA, and that the RG head model
      based LORETA is desirable if high localization accuracy is needed.

PMID- 15715423
TI  - Real time control of the spatial selectivity during laser treatment of a
      biological surface.
AB  - We propose a new irradiation technique to improve the spatial selectivity and the
      dose control during a laser treatment of a biological surface. The technique is
      based on the use of a spatial light modulator to project a rectangular laser
      image of 8 mm x 5 mm. The spatial distribution of the irradiation is controlled
      in real time by image analysis applied to the acquired image of the surface to be
      treated. The aim is to discriminate between the target areas to be irradiated and
      the surrounding parts to be preserved. The resolution is about 12 microm and is
      limited by the resolution of the camera and the spatial light modulator. For
      treatments of a large surface we use an intensity correlator to measure the
      displacement and to avoid an unwanted second irradiation on a target.

PMID- 15715424
TI  - Human epithelial cells increase their rigidity with ageing in vitro: direct
      measurements.
AB  - The decrease in elasticity of epithelial tissues with ageing contributes to many
      human diseases. This change was previously attributed to increased crosslinking
      of extracellular matrix proteins. Here we show that individual human epithelial
      cells also become significantly more rigid during ageing in vitro. Using atomic
      force microscopy (AFM), we found that the Young's modulus of viable cells was
      consistently increased two- to four-fold in older versus younger cells. Direct
      visualization of the cytoskeleton using a novel method involving the AFM
      suggested that increased rigidity of ageing cells was due to a higher density of
      cytoskeletal fibres. Our results identify a unique mechanism that might
      contribute to the age-related loss of elasticity in epithelial tissues.

PMID- 15715425
TI  - Tumour resistance to cisplatin: a modelling approach.
AB  - Although chemotherapy has revolutionized the treatment of haematological tumours,
      in many common solid tumours the success has been limited. Some of the reasons
      for the limitations are: the timing of drug delivery, resistance to the drug,
      repopulation between cycles of chemotherapy and the lack of complete
      understanding of the pharmacokinetics and pharmacodynamics of a specific agent.
      Cisplatin is among the most effective cytotoxic agents used in head and neck
      cancer treatments. When modelling cisplatin as a single agent, the properties of
      cisplatin only have to be taken into account, reducing the number of assumptions
      that are considered in the generalized chemotherapy models. The aim of the
      present paper is to model the biological effect of cisplatin and to simulate the
      consequence of cisplatin resistance on tumour control. The 'treated' tumour is a
      squamous cell carcinoma of the head and neck, previously grown by computer-based
      Monte Carlo techniques. The model maintained the biological constitution of a
      tumour through the generation of stem cells, proliferating cells and non
      proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss
      factor, thymidine labelling index) were also consistent with the literature. A
      sensitivity study on the contribution of various mechanisms leading to drug
      resistance is undertaken. To quantify the extent of drug resistance, the
      cisplatin resistance factor (CRF) is defined as the ratio between the number of
      surviving cells of the resistant population and the number of surviving cells of
      the sensitive population, determined after the same treatment time. It is shown
      that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA
      adducts formed, and a sigmoid-like dependence between CRF and the percentage of
      cells killed in resistant tumours. Drug resistance is shown to be a cumulative
      process which eventually can overcome tumour regression leading to treatment
      failure.

PMID- 15715426
TI  - Quantitative analysis of patient-specific dosimetric IMRT verification.
AB  - Patient-specific dosimetric verification methods for IMRT treatments are
      variable, time-consuming and frequently qualitative, preventing evidence-based
      reduction in the amount of verification performed. This paper addresses some of
      these issues by applying a quantitative analysis parameter to the dosimetric
      verification procedure. Film measurements in different planes were acquired for a
      series of ten IMRT prostate patients, analysed using the quantitative parameter,
      and compared to determine the most suitable verification plane. Film and ion
      chamber verification results for 61 patients were analysed to determine long-term
      accuracy, reproducibility and stability of the planning and delivery system. The
      reproducibility of the measurement and analysis system was also studied. The
      results show that verification results are strongly dependent on the plane
      chosen, with the coronal plane particularly insensitive to delivery error.
      Unexpectedly, no correlation could be found between the levels of error in
      different verification planes. Longer term verification results showed consistent
      patterns which suggest that the amount of patient-specific verification can be
      safely reduced, provided proper caution is exercised: an evidence-based model for
      such reduction is proposed. It is concluded that dose/distance to agreement
      (e.g., 3%/3 mm) should be used as a criterion of acceptability. Quantitative
      parameters calculated for a given criterion of acceptability should be adopted in
      conjunction with displays that show where discrepancies occur. Planning and
      delivery systems which cannot meet the required standards of accuracy,
      reproducibility and stability to reduce verification will not be accepted by the
      radiotherapy community.

PMID- 15715427
TI  - Incorporating organ movements in inverse planning: assessing dose uncertainties
      by Bayesian inference.
AB  - We present a method to calculate dose uncertainties due to inter-fraction organ
      movements in fractionated radiotherapy, i.e. in addition to the expectation value
      of the dose distribution a variance distribution is calculated. To calculate the
      expectation value of the dose distribution in the presence of organ movements,
      one estimates a probability distribution of possible patient geometries. The
      respective variance of the expected dose distribution arises for two reasons:
      first, the patient is irradiated with a finite number of fractions only and
      second, the probability distribution of patient geometries has to be estimated
      from a small number of images and is therefore not exactly known. To quantify the
      total dose variance, we propose a method that is based on the principle of
      Bayesian inference. The method is of particular interest when organ motion is
      incorporated in inverse IMRT planning by means of inverse planning performed on a
      probability distribution of patient geometries. In order to make this a robust
      approach, it turns out that the dose variance should be considered (and
      minimized) in the optimization process. As an application of the presented
      concept of Bayesian inference, we compare three approaches to inverse planning
      based on probability distributions that account for an increasing degree of
      uncertainty. The Bayes theorem further provides a concept to interpolate between
      patient specific data and population-based knowledge on organ motion which is
      relevant since the number of CT images of a patient is typically small.

PMID- 15715428
TI  - Preliminary evaluation of implantable MOSFET radiation dosimeters.
AB  - In this paper, we report on measurements performed on a new prototype implantable
      radiation detector that uses metal-oxide semiconductor field effect transistors
      (MOSFETs) designed for in vivo dosimetry. The dosimeters, which are encapsulated
      in hermetically sealed glass cylinders, are used in an unbiased mode during
      irradiation, unlike other MOSFET detectors previously used in radiotherapy
      applications. They are powered by radio frequency telemetry for dose
      measurements, obviating the need for a power supply within each capsule. We have
      studied the dosimetric characteristics of these MOSFET detectors in vitro under
      irradiation from a 60Co source. The detectors show a dose reproducibility
      generally within 5% or better, with the main sources of error being temperature
      fluctuations occurring between the pre- and post-irradiation measurements as well
      as detector orientation. A better temperature-controlled environment leads to a
      reproducibility within 2%. Our preliminary in vitro results show clearly that
      true non-invasive in vivo dosimetry measurements are feasible and can be
      performed remotely using telemetric technology.

PMID- 15715429
TI  - Dose calculation of 142Pr microspheres as a potential treatment for arteriovenous
      malformations.
AB  - Arteriovenous malformation (AVM), especially cryptic AVM, can cause highly
      variable cerebral neurological defects. Injection of 142Pr microspheres into
      arteries feeding an AVM in order to simulate radio-embolism has been proposed as
      a novel treatment method. To investigate optimization of radiation dose to the
      clinically important arterial wall area, preliminary dosimetric studies have been
      performed. Monte Carlo calculations were performed for simulated arteries filled
      with microspheres packed by random packing. Arterial radii from 0.05 mm to 3 mm
      and microsphere radii from 0.01 mm to 0.7 mm were used in the simulation. For
      constant arterial size, dose varied significantly with microspheres radius. Inter
      arterial effect was also simulated using simplified geometry. For the inter
      arterial sites, the dose rate was calculated between two arteries of the same
      size parallel to each other. The dose increased significantly for large arteries
      (>1 mm radius) filled with large microspheres (>0.3 mm radius). The dose increase
      between small arteries (<0.3 mm radius) was not as significant as that between
      large arteries. Overall results indicate that arterial size and microsphere size
      significantly affect the dose profile. This factor should be taken into account
      in future clinical applications.

PMID- 15715430
TI  - Characteristics of boron-dose enhancer dependent on dose protocol and 10B
      concentration for BNCT using near-threshold 7Li(p,n)7Be direct neutrons.
AB  - The dependence of boron-dose enhancer (BDE) characteristics on dose protocol and
      10B concentration was evaluated for BNCT using near-threshold 7Li(p,n)7Be direct
      neutrons. The treatable protocol depth (TPD) was utilized as an evaluation index.
      MCNP calculations were performed for near-threshold 7Li(p,n)7Be at a proton
      energy of 1.900 MeV and for a polyethylene BDE. The effect of dose protocol on
      BDE characteristics was reflected in terms of the optimum BDE thickness needed
      for maximum TPD which was found to be independent of the treatable dose but was
      observed to vary for different combinations of the tolerance doses for heavy
      charged particles and gamma rays. For the 10B concentration dependence, the TPD
      was increased by increasing the T/N ratio, i.e., the ratio of the 10B
      concentration in the tumour (10B(Tumour)) to that in the normal tissue
      (10B(Normal)), and by increasing 10B(Tumour) and 10B(Normal) at constant T/N
      ratio. It was found that the use of BDE becomes unnecessary from the viewpoint of
      increasing the TPD, when 10B(Tumour) is over a certain level which is decided by
      the conditions of the dose protocol.

PMID- 15715431
TI  - Dose properties of x-ray beams produced by laser-wakefield-accelerated electrons.
AB  - Given that laser wakefield acceleration (LWFA) has been demonstrated
      experimentally to accelerate electron beams to energies beyond 25 MeV, it is
      reasonable to assess the ability of existing LWFA technology to compete with
      conventional radiofrequency linear accelerators in producing electron and x-ray
      beams for external-beam radiotherapy. We present calculations of the dose
      distributions (off-axis dose profiles and central-axis depth dose) and dose rates
      of x-ray beams that can be produced from electron beams that are generated using
      state-of-the-art LWFA. Subsets of an LWFA electron energy distribution were
      propagated through the treatment head elements (presuming an existing design for
      an x-ray production target and flattening filter) implemented within the EGSnrc
      Monte Carlo code. Three x-ray energy configurations (6 MV, 10 MV and 18 MV) were
      studied, and the energy width deltaE of the electron-beam subsets varied from 0.5
      MeV to 12.5 MeV. As deltaE increased from 0.5 MeV to 4.5 MeV, we found that the
      off-axis and central-axis dose profiles for x-rays were minimally affected (to
      within about 3%), a result slightly different from prior calculations of electron
      beams broadened by scattering foils. For deltaE of the order of 12 MeV, the
      effect on the off-axis profile was of the order of 10%, but the central-axis
      depth dose was affected by less than 2% for depths in excess of about 5 cm beyond
      d(max). Although increasing deltaE beyond 6.5 MeV increased the dose rate at
      d(max) by more than 10 times, the absolute dose rates were about 3 orders of
      magnitude below those observed for LWFA-based electron beams at comparable
      energies. For a practical LWFA-based x-ray device, the beam current must be
      increased by about 4-5 orders of magnitude.

PMID- 15715432
TI  - Genome sequence comparative analysis of long arm and short arm of human X
      chromosome.
AB  - 30% of the genes tested on Xp escaped inactivation, whereas less than 3% of the
      genes on Xq escaped inactivation. To investigate the molecular mechanism involved
      in the propagation and maintenance of X chromosome inactivation and escape, the
      long arm and short arm of the X chromosome were compared for RNA binding density.
      Nucleotide sequences on the X chromosome were divided into 50 kb per segment that
      was recorded as a set of frequency values of 7-nucleotide (7 nt) strings using
      all possible 7 nt strings (4(7) = 16 384). 120 genes highly expressed in the
      tonsil germinal center B cells were selected for calculating the 7 nt string
      frequency values of all introns (intron 7nt). Intron 7nt was considered RNAs (RNA
      population) that simulated the total of small RNA fragments in cells. Knowing the
      7 nt frequency values of DNA segments and the intron 7nt, we can calculate the
      binding density of DNA segments to the intron 7nt that was termed as RNA binding
      density. The RNA binding density was determined by the amount of complement
      sequences. The more amount of complement sequences, the more density of RNA
      binding. The RNA binding density simulated the total of small RNA fragments bound
      to the DNA segment. Several principal characteristics were observed for the first
      time: (1) The mean value of RNA binding density of DNA segments on Xp was
      significantly higher than that on Xq ( P < 0.001); (2) The numbers of DNA
      segments highly binding RNAs were more on Xp than on Xq (P < 0.001); (3) The
      clusters of RNA highly binding DNA segments were associated with regions in which
      genes escape inactivation. It has been suggested that RNAs activate genes and the
      interaction of RNA-DNA in cells are extensive, for example, RNAs increase DNase I
      sensitivity of DNA, there is plenty of nonprotein-coding RNAs in cells, the
      binding specificity of DNA-RNA is far higher than that of DNA-protein and the
      affinity of DNA with RNA is increased, as compared with DNA. The nonrandom
      properties of distribution of RNA highly binding segments between Xp and Xq,
      combined with the finding of RNA activating genes, provide a strong evidence that
      RNA highly binding segments may serve as DNA signals to propagate activation
      along a chromosome and vice versa, the DNA segments that less bind RNAs may
      silence the genes.

PMID- 15715433
TI  - Association of Sst I polymorphism in apolipoprotein C3 gene with
      hypertriglyceridaemia in coronary atherosclerotic heart disease and type II
      diabetes mellitus in Chinese population.
AB  - Several independent population studies have reported that the apolipoprotein C3
      (APOC3) Sst I polymorphism in apolipoprotein (apo) A1 /C3/A4/A5 gene cluster is
      associated with Hypertriglyceridaemia (HTG). HTG is a known risk factor for
      coronary atherosclerotic heart disease(CHD)and type II diabetes mellitus (non
      insulin-dependent diabetes, NIDDM). The aim of this study is to investigate the
      association between the APOC3 gene Sst I polymorphism and the
      hypertriglyceridaemia in CHD and NIDDM in Chinese population. The genotype and
      allele frequencies of APOC3 Sst I polymorphism (S1/S2) were analyzed by PCR
      restriction fragment length polymorphism in 267 CHD patients, 246 NIDDM patients
      and 491 unrelated healthy control individuals. The frequencies of minor allele 52
      in CHD group, NIDDM group and control group were 0.301, 0.307 and 0.286,
      respectively. Compared with controls, there was no significant difference in
      distribution of genotype and allele frequencies of Sst I polymorphic site in CHD
      patients and NIDDM patients, respectively. However, the frequency of S1 S2
      genotype in the HTG subgroup was significantly higher than that of the normal
      triglyceridaemia subgroup (NTG) in CHD patients (0.542 > 0.357, chi2 = 8.77, P =
      0.0124). In NIDDM patients, the frequency of S2 S2 genotype in the HTG subgroup
      was significantly high, compared with that in the NTG subgroup (0.200 > 0.055,
      chi2 = 20.21, P = 0.0000), and there was significantly difference in the
      distribution of allele frequencies in subgroups of NTG and HTG (chi2 = 19.86, P =
      0.0000). The level of triglyceride (TG) in S1 S2 genotype patients of CHD group
      were higher than that of S1 S1 genotype patients (P = 0.036). In NIDDM and
      controls groups, S2 S2 genotype individuals exhibited a significant increase in
      plasma TG concentrations, respectively compared with S1 S1 and S1 S2 genotype
      individuals of each group (P < 0.01). The minor allele S2, which was associated
      with both CHD with HTG and NIDDM with HTG and may contribute to the
      susceptibility of hypertriglyceridemia in CHD and NIDDM patients, may be one of
      the genetic predispositions to both CHD with HTG and NIDDM with HTG in Chinese
      population.

PMID- 15715434
TI  - Molecular cloning and sequence analysis of full-length growth hormone cDNAs from
      six important economic fishes.
AB  - In this study,the full-length cDNAs of GH (Growth Hormone) gene was isolated from
      six important economic fishes, Siniperca kneri, Epinephelus coioides, Monopterus
      albus, Silurus asotus, Misgurnus anguillicaudatus and Carassius auratus gibelio
      Bloch. It is the first time to clone these GH sequences except E. coioides GH.
      The lengths of the above cDNAs are as follows: 953 bp, 1 023 bp, 825 bp, 1 082
      bp, 1 154 bp and 1 180 bp. Each sequence includes an ORF of about 600 bp which
      encodes a protein of about 200 amino acid: S. kneri, E. coioides and M. albus GHs
      of 204 amino acid, S. asotus GH of 200 amino acid, M. anguillicaudatus and C.
      auratus gibelio GHs of 210 amino acid. Then detailed sequence analysis of the six
      GHs with many other fish sequences was performed. The six sequences all showed
      high homology to other sequences, especially to sequences within the same order,
      and many conserved residues were identified, most localized in five domains. The
      phylogenetic trees (MP and NJ) of many fish GH ORF sequences (including the new
      six) with Amia calva as outgroup were generally resolved and largely congruent
      with the morphology-based tree though some incongruities were observed,
      suggesting GH ORF should be paid more attention to in teleostean phylogeny.

PMID- 15715435
TI  - [Screening genes related to 'black' character in wu-ding chicken by delta
      differential display].
AB  - The 'black' character is a cardinal character of black chicken that is very
      important to the medical value and economical value of black chicken. The study
      compared gene expression between black chicken and non-black chicken by delta
      differential display method, and obtained twenty-nine expressed sequence
      tags(ESTs) by extraction, amplification, purification, northern blotting, cloning
      and sequencing of gel-embedded DNA. Of twenty-nine ESTs, eight ESTs have high
      similarity rate with known gene in chicken-beta-trepomyosin gene, cardiac myosin
      alkali light chain gene, insertionally activated c-Ha-ras oncogene, fra-2
      oncogene, 16S rRNA gene and mitochondrion genome sequence, respectively, with
      similarity rate 97%,100%, 98%, 98%, 98%, 99%, 99% and 97%. Five ESTs have high
      similarity rate with human TTN gene, human phosphoglucomutase 5 gene, human or
      mouse signal recongnition particle 54 kD gene, human or mouse
      ribonuclease/angiogenin inhibitor gene, respectively, with similarity rate 82%,
      82%, 87%, 99% and 99%. Their homologous genes in chicken are still not cloned.
      Thirteen ESTs are novel gene fragments. Of thirteen ESTs, nine ESTs have high
      similarity with ESTs in database. Four ESTs have not high similarity with any EST
      in database. The results of gene expression analysis show that one known gene
      (insertionally activated c-Ha-ras oncogene) fragment and one novel gene fragment
      are expressed in all non-black chicken and are not expressed in all black
      chicken, and that one known gene (signal recongnition particle 54 kD gene)
      fragment is expressed in all black chicken and is not expressed in all non-black
      chicken. According to these results, we conclude that the expression of
      insertionally activated c-Ha-ras oncogene, signal recongnition particle 54 kD
      gene and one novel gene are related to the 'black' character in chicken.

PMID- 15715436
TI  - [Study on BMP15 and GDF9 as candidate genes for prolificacy of Small Tail Han
      sheep].
AB  - Bone morphogenetic protein 15 (BMP15) gene and growth differentiation factor 9
      (GDF9) gene which control the fecundity of Belclare and Cambridge ewes were
      studied as candidate genes on the prolificacy of Small Tail Han sheep. Single
      nucleotide polymorphism of GDF9 gene and BMP15 gene was detected in both high
      fecundity sheep breeds (Small Tail Han sheep and Hu sheep) and low fecundity
      sheep breeds (Dorset sheep, Texel sheep and German Mutton Merino sheep) by PCR
      RFLP. The results showed that the G8 mutation (C --> T) of GDF9 gene and the B4
      mutation (G --> T) of BMP15 gene were not detected in five sheep breeds. There
      was the same B2 mutation (C --> T) of BMP15 gene in Small Tail Han sheep as that
      in Belclare and Cambridge ewes. The same B2 mutation did not exist in other four
      sheep breeds. Concerning the B2 mutation of BMP15 gene, AA and AB genotypes were
      detected in Small Tail Han sheep, frequency of A allele was 0. 734, frequency of
      B allele was 0.266. The BMP15 B2 genotype distributions were high significantly
      different (P < 0.001) between Small Tail Han sheep and other four sheep breeds.
      The ewes with heterozygous mutant AB had 0.62 (P < 0.01) lambs more than those
      with wild homozygous type AA in Small Tail Han sheep. These results indicated
      that the B2 mutation of BMP15 gene had significant effect on the fecundity of
      Small Tail Han sheep and ruled out the possibility that the fecundity of Small
      Tail Han sheep was affected by the G8 mutation of GDF9 gene and the B4 mutation
      of BMP15 gene.

PMID- 15715437
TI  - [Effect of interleukin-6 on gene expression of certain cytokines during wound
      healing process of mouse skin].
AB  - To examine the effect of the interlukin-6 (IL-6) in wound healing process, gene
      expression profiles of cytokines including interlukin-1alpha (IL-1alpha),
      interlukin-1beta (IL-1beta), keratinocyte chemoattractant (KC), macrophage
      inflammatory protein-1alpha (MIP-1alpha), and macrophage inflammatory protein-2
      (MIP-2) during the skin wound healing on the IL-6(+/+) and IL-6(-/-) mice were
      detected using immunochemical staining and RT-PCR methods at different phases
      after wound. The results showed that these cytokines were expressed at early
      phage after wound, and a expressing peak were found on the third day after wound,
      and decreased on the sixth day after wound. Meanwhile, on the third and sixth day
      after wound, all the levels of the five cytokines expressed of the IL6(-/-) mice
      were significantly lower than those of the IL-6(+/+) mice, but on the first day
      after wound, only the levels of MIP-1alpha and KC of the IL-6(-/-) mice were
      lower. The process of skin wound healing was later in IL-6(-/-) mice than that in
      IL-6(+/+) mice, but it was complete in IL-6(-/-) mice. These results showed that
      IL-6 induce expression of the other five cytokines detected, and advance the
      repair of the wound on skin of mice, but in the mice of IL-6 deletion, the wound
      healing process was not disturbed significantly.

PMID- 15715438
TI  - [Recombinant analysis of classical swine fever virus].
AB  - To study the possible recombinant relationship among differently derived
      classical swine fever virus, the coding regions of 21 isolates were analyzed to
      detect recombination and breakpoints through gene trees comparison and quartet
      analyses. The results show nucleotide area corresponding to E0, E1 and E2 as a
      possible recombinant tract between ALD ( D49532) and GPE-(D49533) while NS5A-NS5B
      of the isolate 39 (AF407339) appears to be derived from a virulent Shimen strain
      (AF092448) sequence. This suggests that intertypic exchanges of genetic materials
      during mixed infections under natural or laboratorial conditions can lead
      classical swine fever virus to adapt to the changes of host environment.

PMID- 15715439
TI  - [Analysis of heading time genotype for a rice photoperiod and thermo--sensitive
      male sterile line PeiAi64S].
AB  - PeiAi64S, a photoperiod and thermo-sensitive genic male sterile, has been wildly
      applied to hybrid rice seed production in China, but its photoperiod-sensitivity
      gene for heading date in this sterile line was still unknown. This definitely
      limited the further use of this sterile line in breeding practice and re
      production of hybrid seeds. To solve this problem, using heading time nearly
      isogenic lines EGO - EG7, ER - LR, T65 - T65m and six heading date QTL-isogenic
      lines, NIL (Hd1) - NIL (Hd6) with the genes of Nipponbare but Hd1 - Hd6 genes
      from Kasalath respectively, we performed a genetic analysis of PeiAi64S with
      special reference to photoperiod-sensitivity loci, in natural long days at
      Nanjing (32 degrees N) where the average day-length is about 14 h and in natural
      short days at Linshui county, Hainan province(18 degrees 29'N), where the average
      day-length is about 11.6 h during the course of rice growing respectively. The F1
      and F2 generations from the crosses 'PeiAi64S x heading time nearly isogenic
      lines' were subjected to genetic analyses. Experimental results showed that
      PeiAi64S carries photoperiod-sensitivity allele gene E1 and E3 and dominant
      earliness gene Ef-1 in E1 and E3 and Ef-1 loci, respectively, and a photoperiod
      insensitivity allele Se-1 degrees in Se-1 locus. Meanwhile, the photoperiod
      sensitivity gene E1 and photoperiod-insensitivity gene Se-1e in PeiAi64S were
      also identified by crossing with the NIL(Hd1) and NIL(Hd4). In addition, a
      recessive inhibitor for photoperiod-sensitive gene E1 or Se-1(n) and other
      modified photoperiod-sensitive genes: i-Se-1, E3, Hd3 (En-Se-1), Hd5 and Hd6,
      were identified in PeiAi64S by crossing with QTL nearly isogenic lines: NIL(Hd2),
      NIL (Hd3), NIL (Hd5) and NIL( Hd6), The results indicated that the genotype of
      PeiAi64S's heading date was: E1E1e2e2E3E3Se-1(e)Se-1(e)Ef-1 Ef-1 i-Se-1 i-Se-1.

PMID- 15715440
TI  - [Wheat transformation by electroporation with ring electrode].
AB  - Electroporation has been used effectively to deliver DNA into the tissue of
      intact wheat immature embryos. The physical parameters of electroporation were
      770 V/cm field strength, 800 microF capacitor and 100 microg/mL of plasmid DNA,
      containing bar and GUS gene. The electroporation was carried out by a portable
      and permanent ring electrode that can be fitted into the wells of 24-well plates.
      The samples were pulsed three times. Integration of the introduced genes into the
      genome of transgenic wheat plants was shown by PCR and Southern blot analysis.
      Transformation frequency was 7.5%, that is higher than that of the 4.2% frequency
      by microprojectile bombardment.

PMID- 15715441
TI  - [Cloning and expression analysis of two Rac genes from cotton (Gossypium hirsutum
      L.)].
AB  - Plant Rac proteins belong to an important group of signal switches anchoring on
      membranes, involved in various physiological processes including cell polar
      growth, synthesis of secondary wall, resistance response and hormone signaling.
      In the attempt to elucidate the molecular mechanism of initiation and elongation
      of cotton fiber, two cotton Rac protein genes, designated as GhRacA and GhRacB,
      were amplified from elongating fibers and cloned. It was demonstrated that, the
      cDNA of GhRacA contained 959 bp and encoded a putative polypepetide of 211 aa,
      while GhRacB was 920 bp in length, encoding a predicted protein of 195 aa. These
      two cotton Rac proteins, GhRacA and GhRacB, contained conserved regions involved
      in GTP/GDP binding and activation, an effector region and a polybasic region. A
      conserved prenylation site CSIL was found in GhRacB, while no apparent
      prenylation site was discovered in GhRacA. Sequence comparisons showed that
      GhRacA and GhRacB were two novel Rac proteins from cotton. The expression
      patterns of GhRacA and GhRacB was analyzed by RT-PCR. It was demonstrated that
      these two Rac protein genes were both expressed in root, hypocotyls, stem, leaf
      and fibers, and the highest level of transcripts was to accumulate in the fibers
      at the stage of initiation and elongation, suggesting that the two Rac genes,
      GhRacA and GhRacB, might play an important role in the early stage of fiber
      development.

PMID- 15715442
TI  - Diallel analysis of superior fiber quality properties in selected upland cottons.
AB  - Twenty cross combinations were produced using a complete diallel-mating system
      with five varieties or lines that differed in fiber properties in Upland cotton
      to determine the inheritance and breeding merits of superior fiber properties.
      Evaluations of parents and F1 ' s were conducted in two years. The results showed
      that fiber length uniformity was greatly affected by environmental factors,
      whereas the other fiber properties were mainly controlled by genetic factors.
      There were no significant interaction effect of environment with genotype for
      fiber strength or length, but there were significant environment interactions
      with additive and maternal affects for Micronaire, and with the dominance effects
      for elongation. There were no maternal effect, and additive effects predominated
      for the all fiber properties. Additive heritability was high for fiber strength
      and length, 77.6% and 73.2% respectively; for Micronaire, it was 45.2%, while the
      dominance effect was 11.5%, which was the highest among fiber properties.
      Micronaire had significant heterosis over mid-parent based on population mean
      (3.2%), while the other fiber properties showed no heterosis. Therefore, the
      performance of fiber properties in F1 ' s can be predicted from the average value
      of both parents. Since the additive heritability of strength, length, and
      fineness of fiber were high, these traits can be selected in early generations in
      breeding for high quality fiber properties.

PMID- 15715443
TI  - [Cloning and analysis of LMW-GS genes from Triticum aestevum ssp. tibetanum
      Shao].
AB  - The full coding regions (open reading frame,ORF) of LMW-GS genes were amplified
      from Triticum aestevum ssp. tibetanum Shao accession AS908 by using the primer
      pairs W1227 and W1228,which were designed according to wheat LMW-GS conservative
      domains. The amplified DNA fragments were separated and recovered from agrose
      gel,subsequently ligated into pBluescript SK( +/-)-T vector, and then transformed
      into E. coil strain DH10B. Three positive clones were screened out and sequenced.
      Among which, Tibet1 (GenBank accession No:AY299457) and Tibet2 (GenBank accession
      No: AY299458) are two expressed LMW glutenin genes. Their coding regions are 1
      041 bp and 901 bp, and encode two mature proteins with 326 and 281 amino acid
      residues, respectively. Tibet3 (GenBank accession No:AY299459) is a pseudogene
      due to that two stop codons are in its coding region. Squence multipule alignment
      analysis suggested that Tibet1, Tibet2 and Tibet3 have the higher similarity in
      their structure and quality functions with the known LMW-GS genes with GenBank
      accession No: AY214450, AJ293099 and AB062871 encoded by Glu-D3, Glu-A 3 and Glu
      A3, respectively.

PMID- 15715444
TI  - [Genetic analysis of RNA-mediated virus resistance in transgenic tobacco].
AB  - RNA-mediated virus resistance is an effective way to obtain virus resistant
      plants and is regarded as a potential strategy with application value in plant
      resistant virus breeding because of its advantage of high biosafety and long
      duration. Whether the resistance can inherit stably is a critical factor
      affecting its application in agriculture. In this paper, several T0 progeny
      transgenic plants with different resistant levels and with different transgene
      copy numbers were selected for further study. The results showed that the
      inheritance of the transgene in T0 susceptible transgenic plants containing 1 -2
      transgene copies followed Mendelian segregation pattern of single gene
      inheritance in their progenies. Resistant transgenic plants, which contained 4 -6
      transgene copies, followed 15:1 and 63:1 segregation patterns in the T1 progeny.
      Transgene recombination and re-organization in the plant genome was observed,
      which resulted in unstable inheritance of the transgene in the progenies.
      Homozygous resistant transgenic plants were obtained after 3 to 4 generations in
      the progeny. Analysis of the transgene integration pattern indicated that most of
      the highly resistant plants contained inverted repeat (IR) sequences of the
      transgene.

PMID- 15715445
TI  - [Research advances on the mechanism of RNA silencing in plants].
AB  - RNA silencing is a supervising mechanism in eukaryote which can prevent virus
      duplication, repress transposition of transposon and regulate gene expression.
      Compared with that in animals, RNA silencing in plants shows some differences in
      the function of RdRP, in bi-directional transitive RNAi, and in systemic
      propagation, etc. Meanwhile,the endogenous small RNAs in plants are more diverse
      than those in animals. In this paper, it is reviewed of the mechanism of RNA
      silencing in plants and the possibility of its use in plant functional Genomics.

PMID- 15715446
TI  - Hydrogel-coated coils for the treatment of cerebral aneurysms: preliminary
      results.
AB  - OBJECT: The authors present a retrospective analysis of their initial experience
      with the recently developed MicroVention HydroCoil to treat patients with
      cerebral aneurysms. Unlike the bare metal coils initially available for
      endovascular treatment of aneurysms, HydroCoils have a layer of hydrogel polymer
      surrounding a platinum metallic core. The hydrogel polymer expands soon after
      making contact with blood. The expanded hydrogel polymer provides increased
      volumetric filling compared with bare metal coils and offers a more biocompatible
      surface, as demonstrated in animal models. METHODS: Over a 17-month period, the
      authors used HydroCoils to treat 30 patients with 33 aneurysms. All patients had
      been treated at least 6 months prior to data analysis. Initial treatment results
      as well as records of clinical and angiographic follow up were reviewed. Six
      month posttreatment angiograms were available for 25 patients. CONCLUSIONS: The
      HydroCoils were implanted with few complications. On angiographic follow up, a
      clearly defined radiolucent separation of the coils from the parent artery was
      noted in many of the aneurysms treated. The authors have not previously observed
      angiographically demonstrated lucencies separating the coils from the parent
      artery. This frequent, but not consistent, appearance on follow-up angiograms
      obtained in this study indicates that HydroCoils support significant neointimal
      formation across the neck of treated aneurysms. The preliminary results indicate
      that HydroCoils can be used safely and effectively to treat aneurysms and that
      these devices may allow for improved aneurysm filling.

PMID- 15715447
TI  - Evolution of endovascular therapy for aneurysm treatment. Historical overview.
AB  - The endovascular treatment of intracranial aneurysms has recently become an
      established therapeutic option. The foundation of this treatment modality was
      laid by the work done in ground-breaking cases, combined with technological
      advances since the first half of the 19th century. In this historical overview
      the authors describe the steps taken by the early pioneers and the results of
      their work, which was often done under challenging circumstances. The work of
      these predecessors established the stepping-stones for constant development and
      refinement for those who have come after them, eventually evolving into the
      procedures used today. Endovascular treatment of intracranial aneurysms is only
      possible because of the work of these innovators.

PMID- 15715448
TI  - Endovascular management of intracranial vertebral artery dissecting aneurysms.
AB  - OBJECT: Intracranial vertebral artery (VA) dissecting aneurysms often present
      with severe subarachnoid hemorrhage (SAH) and dramatic neurological injury. The
      authors reviewed the management of 23 cases in an effort to evaluate treatment
      efficacy and outcomes. METHODS: The records of 23 patients who underwent
      endovascular treatment were reviewed to determine symptoms, type of therapy,
      complications, and clinical outcomes. All patients were evaluated using records
      kept in a prospectively maintained database. Ten men and 13 women (age range 35
      72 years; mean age 49 years) were treated over an 8-year period. Twelve patients
      presented with poor-grade SAH, five with good-grade SAH, three with headache, and
      two with stroke. The other patient's aneurysm was discovered incidentally.
      Treatment included coil occlusion of the artery at the aneurysm in 21 patients
      and stent-assisted coil placement in two. Parent artery sacrifice was successful
      in all cases, whereas both patients treated with stent-assisted coil insertion
      suffered recurrences. No patient sustained permanent complications as a result of
      treatment. Two patients died due to the severity of their original SAH. Findings
      were normal in 14 patients on follow-up review (including five of the 12
      presenting with poor-grade SAH), five had fixed neurological deficits but were
      able to care for themselves, and one was permanently disabled. CONCLUSIONS:
      Despite their often aggressive neurological presentation, intracranial VA
      dissecting aneurysms can be managed safely with coil occlusion of the lesion
      and/or parent artery. Even patients presenting in poor neurological condition may
      improve dramatically.

PMID- 15715449
TI  - Treatment of wide-necked cerebral aneurysms with the Neuroform2 Treo stent. A
      prospective 6-month study.
AB  - OBJECT: Until recently, wide-necked aneurysms were not considered amenable to
      treatment with coil embolization. The recent introduction of intracranial stents
      has provided a method of preventing coil migration out of wide-necked aneurysms.
      The Neuroform2 Treo is a modification of the Neuroform stent; the new version has
      a higher metal/artery ratio. The authors' initial experience with the use of this
      stent in combination with coil embolization to treat widenecked intracranial
      aneurysms is reported and technical considerations are discussed. METHODS: The
      authors' first 10 consecutive patients with wide-necked intracranial aneurysms
      were included in this study. Inclusion criteria restricted the group to adult
      patients with wide-necked intracranial aneurysms (ruptured and unruptured
      lesions). A wide neck was defined as a dome/neck ratio of less than 2 or a neck
      that was 4 mm or wider as measured on angiograms. Immediate postprocedure
      angiography studies were performed to determine successful coil occlusion of the
      aneurysm as well as patency of the parent vessel. Six-month follow-up angiograms
      were obtained in all patients. Ten aneurysms with poor dome/neck ratios (< 2)
      were studied in 10 patients. In all cases the stent was delivered to the aneurysm
      site and positioned without difficulty. No branch artery compromise was observed.
      A technical difficulty occurred in one case, with prolapse of a coil into the
      parent vessel, which was successfully corrected with no adverse clinical effects.
      There were no clinical or neurological complications associated with endovascular
      treatment of aneurysms in this series. One patient required further coil
      embolization because of findings on the 6-month follow-up cerebral angiogram.
      CONCLUSIONS: The Neuroform2 Treo navigates similarly to the Neuroform2, with the
      advantage of increased aneurysm neck coverage. This feature may lower the
      retreatment rates for wide-necked cerebral aneurysms.

PMID- 15715450
TI  - Determination of filling volumes in HydroCoil-treated aneurysms by using three
      dimensional computerized tomography angiography.
AB  - OBJECT: Coil embolization of aneurysms has been shown to be as safe and effective
      as surgical clip ligation, but has a higher recurrence rate. Advances in coil
      technology aim to reduce aneurysm recurrence by coating the devices with
      biological substances. An example of this is MicroVention's HydroCoil, which is a
      platinum coil coated with hydrogel that improves filling volumes by swelling when
      it contacts blood. The goal of this study was to determine whether this new coil
      type significantly reduced or prevented recurrences of aneurysms. METHODS: The
      authors used three-dimensional computerized tomography angiography to determine
      aneurysm volumes accurately in 12 patients prior to coil embolization. The
      percentage filling volume was subsequently calculated for each aneurysm after
      treatment with HydroCoils and the immediate and 6-month follow-up
      angiographically confirmed occlusions were evaluated. The data demonstrated that
      both anterior and posterior intracranial aneurysms with diameters of 3 to 25 mm
      and volumes of 0.03 to 4.8 ml had filling volumes of 0.02 to 1.36 ml, resulting
      in filling volumes from 23% in a giant ophthalmic artery aneurysm to 80% in a
      small anterior communicating artery aneurysm. All of the aneurysms except for the
      giant one demonstrated stable occlusion on angiographic studies obtained at the 6
      month follow-up review. CONCLUSIONS: HydroCoil embolization of intracranial
      aneurysms is safe and effective for small, large, and very large aneurysms. The
      percentage filling volume is greater than that reported for bare platinum coils
      in every case except the giant aneurysm. Nevertheless, angiographically confirmed
      occlusion is not directly related to percentage filling volume, but rather to the
      ability to occlude the aneurysm neck.

PMID- 15715451
TI  - Combined surgical and endovascular treatment of a recurrent A3-A3 junction
      aneurysm unsuitable for stand-alone clip ligation or coil occlusion. Technical
      note.
AB  - Recurrent aneurysms of the anterior circulation that are distal to the anterior
      communicating artery (ACoA) but proximal to the callosomarginal-pericallosal
      bifurcation can pose a treatment challenge. The authors present one such case, in
      which the patient was treated with pericallosal artery-pericallosal artery (PerA
      PerA) side-to-side bypass, followed by endovascular obliteration of the proximal
      A2 parent vessel. This patient, in whom an ACoA aneurysm had been treated with
      clip ligation 5 years previously, presented with a new, mid-A2, right-sided
      aneurysm with the outflow artery arising from the dome of the lesion. The
      treatment plan included two steps: an interhemispheric transcallosal approach for
      PerA-PerA side-to-side anastomosis; and endovascular coil embolization of the
      right A2 branch feeding the aneurysm. Postprocedure angiography demonstrated no
      ipsilateral aneurysm filling and excellent bilateral distal outflow from the
      anterior cerebral artery (ACA). The use of PerA-PerA side-to-side bypass for the
      treatment of an ACA aneurysm, followed by parent vessel occlusion, offers an
      elegant solution for the treatment of A2 aneurysms that are not amenable to stand
      alone clip ligation or coil occlusion. Such combined methods are invaluable in
      the management of complex cerebral aneurysms.

PMID- 15715452
TI  - Endovascular procedures for treating wide-necked aneurysms.
AB  - Wide-necked aneurysms remain difficult to treat by either open microneurosurgical
      or endovascular procedures. Recent advances in the latter technology, including
      intracranial stents and bioactive coils, now allow an endovascular treatment
      option for cases in which this was not previously available. In this report the
      authors describe the new developments in endovascular technologies that make the
      treatment of wide-necked aneurysms possible. This includes discussion of
      intracranial stents and bioactive coils designed to promote obliteration of the
      aneurysm lumen. In addition, methods for coil insertion in wide-necked aneurysms
      are described, including balloon remodeling and various stent placement
      procedures. Wide-necked aneurysms previously thought to be untreatable by
      endovascular means can now be obliterated, thanks to new devices specifically
      designed for intracranial use.

PMID- 15715453
TI  - Stent placement for the treatment of nonsaccular aneurysms of the vertebrobasilar
      system.
AB  - Vertebrobasilar nonsaccular aneurysms represent a small subset of intracranial
      aneurysms and usually are among the most challenging to be treated. The aim of
      this article was to review the literature and summarize the experience in the
      treatment of these lesions with endovascular approaches. The method of stent
      implantation as it is performed at the authors' institution, including options
      available for vertebral artery access, is described. Practitioners involved in
      the treatment of these lesions should be aware of the potential application of
      intravascular stent placement as well as the associated postprocedure risks and
      potential complications.

PMID- 15715454
TI  - Nondysraphic intramedullary spinal cord lipomas: a review.
AB  - OBJECT: Lipomas of the spinal cord are often a component of spinal dysraphic
      states. Nondysraphic intramedullary spinal cord lipomas are rare, and their
      presentation, in the form of gradually worsening myelopathy, is nonspecific. The
      authors report on the methods used for diagnosis and treatment in patients
      presenting with these lesions at their institution, and they review the relevant
      literature. METHODS: The authors treated 14 patients who presented with
      intramedullary lipomas over a period of 12 years. None of these patients had
      segmentation anomaly or dysraphism of the spine, or any hindbrain anomaly.
      Admission magnetic resonance images were diagnostic in all patients. All tumors
      were located dorsally in the spinal cord, the majority of them in the
      cervicodorsal cord. The lipomas were partially excised with the help of a carbon
      dioxide laser in all patients in an attempt to preserve neurological function.
      All patients attained improvement in their sensory and motor symptoms.
      CONCLUSIONS: Because these lesions do not have a clear-cut margin, it is vital to
      preserve neurological function at the time of surgery, even if it entails
      incomplete resection.

PMID- 15715455
TI  - Prospective analysis of self-perceived quality of life before and after posterior
      fossa decompression in 112 patients with Chiari malformation with or without
      syringomyelia.
AB  - OBJECT: The purpose of this prospective study was to determine if there was a
      difference in the self-perceived quality of life (QOL) before and after surgery
      among patients with Chiari I malformations with or without syringomyelia. Most
      patients with Chiari I malformations report improvement in their QOL after
      decompression surgery; however, specific outcome data have not been empirically
      studied in this patient population. METHODS: One hundred seventy-two consecutive
      patients who underwent posterior fossa decompression based on neuroimaging
      evidence of a Chiari I malformation with or without syringomyelia were
      prospectively offered participation in the study. The Sickness Impact Profile
      (SIP) was chosen as the instrument for data collection. Completed questionnaires
      were returned by 112 patients. A statistically significant improvement (p <
      0.0001) in SIP scores (self-reported QOL) was noted in 84% of participants after
      decompression surgery. Patient age, amount of tonsillar herniation, and evidence
      of syringomyelia before surgery did not correlate with or adversely affect
      outcomes. Among 16 participants who reported worsening in their QOL, anecdotal
      information revealed extraneous factors unrelated to the Chiari I malformation
      that they perceived as negatively influencing their outcome. Among the extraneous
      variables noted by the participants were general health status, unrelated injury,
      other illnesses, and significant stress. CONCLUSIONS: The majority of
      participants who underwent posterior fossa surgery for a Chiari I malformation
      reported significant improvement in their QOL after surgery.

PMID- 15715456
TI  - Superior ophthalmic vein approach to carotid-cavernous fistulas. Technical note.
AB  - Endovascular procedures have revolutionized the treatment of carotid-cavernous
      fistulas through transarterial and transvenous routes. In some circumstances,
      however, traditional endovascular approaches may fail. Direct access to the
      superior ophthalmic vein (SOV) can be used to treat fistulas in this
      circumstance. The authors discuss the technical aspects of direct exposure of the
      SOV for access to the cavernous sinus.

PMID- 15715457
TI  - Minor structural modifications convert the dual TP/CRTH2 antagonist ramatroban
      into a highly selective and potent CRTH2 antagonist.
AB  - Ramatroban, a thromboxane A(2) receptor (TP) antagonist with clinical efficacy in
      asthma and allergic rhinitis, was recently shown to also antagonize the
      prostaglandin D(2) receptor CRTH2. Here we report that minor structural changes
      to ramatroban result in a compound (13) with complete lack of activity on TP but
      sub-nanomolar potency toward CRTH2. This is the first selective CRTH2 antagonist
      described to date, and should prove highly valuable in further elucidating the
      biological significance of CRTH2.

PMID- 15715458
TI  - Fully 2'-modified oligonucleotide duplexes with improved in vitro potency and
      stability compared to unmodified small interfering RNA.
AB  - We have identified a small interfering RNA (siRNA) motif, consisting entirely of
      2'-O-methyl and 2'-fluoro nucleotides, that displays enhanced plasma stability
      and increased in vitro potency. At one site, this motif showed remarkable >500
      fold improvement in potency over the unmodified siRNA. This marks the first
      report of such a potent fully modified motif, which may represent a useful design
      for therapeutic oligonucleotides.

PMID- 15715460
TI  - Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that
      activate p53 in cells.
AB  - HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its
      tumor suppressive functions. A miniaturized thermal denaturation assay was used
      to screen chemical libraries, resulting in the discovery of a novel series of
      benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal
      structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic
      properties. These optimized molecules increase the transcription of p53 target
      genes and decrease proliferation of tumor cells expressing wild-type p53.

PMID- 15715459
TI  - Discovery and structure-activity relationship of quinuclidine benzamides as
      agonists of alpha7 nicotinic acetylcholine receptors.
AB  - A library of benzamides was tested for alpha7 nicotinic acetylcholine receptor
      (nAChR) agonist activity using a chimeric receptor in a functional, cell-based,
      high-throughput assay. From this library, quinuclidine benzamides were found to
      have alpha7 nAChR agonist activity. The SAR diverged from the activity of this
      compound class verses the 5-HT(3) receptor, a structural homologue of the alpha7
      nAChR. PNU-282987, the most potent compound from this series, was also shown to
      open native alpha7 nAChRs in cultured rat neurons and to reverse an amphetamine
      induced gating deficit in rats.

PMID- 15715461
TI  - Improving specificity vs bacterial thymidylate synthases through N-dansyl
      modulation of didansyltyrosine.
AB  - N,O-Didansyl-L-tyrosine (DDT) represented the starting lead for further
      development of novel non-substrate-like inhibitors of bacterial thymidylate
      synthase. The N-dansyl structure modulation led to a submicromolar inhibitor of
      Lactobacillus casei TS (LcTS), which is highly specific with respect to human TS
      (hTS). Using molecular dynamics simulation, a binding mode for DDT vs LcTS was
      predicted, explaining activity and species-specificity along the series.

PMID- 15715462
TI  - Three-dimensional structure-activity relationships of nonsteroidal ligands in
      complex with androgen receptor ligand-binding domain.
AB  - We studied the three-dimensional quantitative structure-activity relationships
      (3D QSAR) of 70 structurally and functionally diverse androgen receptor (AR)
      binding compounds using the comparative molecular similarity indices analysis
      (CoMSIA) method. The compound set contained 67 nonsteroidal analogues of
      flutamide, nilutamide, and bicalutamide whose binding mode to AR was unknown.
      Docking was used to identify the preferred binding modes for the nonsteroidal
      compounds within the AR ligand-binding pocket (LBP) and to generate the ligand
      alignment for the 3D QSAR analysis. The alignment produced a statistically
      significant and predictive model, validated by random group cross-validation and
      external test sets (q(2)(LOO) = 0.656, SDEP = 0.576, r(2) = 0.911, SEE = 0.293;
      q(2)(10) = 0.612, q(2)(5) = 0.571; pred-r(2) = 0.800). Additional model
      validation comes from the CoMSIA maps that were interpreted with respect to the
      LBP structure. The model takes into account and links the AR LBP structure,
      docked ligand structures, and the experimental binding activities. The results
      provide valuable information on intermolecular interactions between nonsteroidal
      ligands and the AR LBP.

PMID- 15715463
TI  - Design, synthesis, and biological evaluation of novel potent and selective
      alphavbeta3/alphavbeta5 integrin dual inhibitors with improved bioavailability.
      Selection of the molecular core.
AB  - A novel series of potent and selective alpha(v)beta(3)/alpha(v)beta(5) dual(
      )()inhibitors was designed, synthesized, and evaluated against several integrins.
      These compounds were synthesized through a Mitsunobu reaction between the
      guanidinium mimetics and the corresponding central templates. Guanidinium
      mimetics with enhaced rigidity (i.e., (2-pyridylamino)propoxy versus the 2-(6
      methylamino-2-pyridyl)ethoxy) led to improved activity toward alpha(v)beta(3).
      Exemplary oral bioavailability in mice was achieved using the indole central
      scaffold. Although, oral bioavailability was maintained when the indole molecular
      core was replace with the bioisosteric benzofuran or benzothiophene ring systems,
      it was found to not significantly impact the integrin activity or selectivity.
      However, the indole series displayed the best in vivo pharmacokinetic properties.
      Thus, the indole series was selected for further structure-activity relationships
      to obtain more potent alpha(v)beta(3)/alpha(v)beta(5) dual antagonist with
      improved oral bioavailability.

PMID- 15715464
TI  - Multivariate design, synthesis, and biological evaluation of peptide inhibitors
      of FimC/FimH protein-protein interactions in uropathogenic Escherichia coli.
AB  - A peptide library targeting protein-protein interactions crucial for pilus
      assembly in Gram negative bacteria has been designed using statistical molecular
      design. A nonamer peptide scaffold was used, with seven positions being varied.
      The selection was performed in the building block space, and previously known
      structure-activity data were included in the design procedure. This resulted in a
      heavily reduced library consisting of 32 peptides which was prepared by solid
      phase synthesis. The ability of the peptides to inhibit the protein-protein
      interaction between the periplasmic chaperone FimC and the pilus adhesin FimH was
      then determined in an ELISA. Novel peptides with the capability to inhibit the
      FimC/FimH protein-protein interaction to the same extent as the native FimC
      peptides were discovered. Multivariate QSAR studies of the response in the ELISA
      gave valuable information on the properties of amino acids which were preferred
      at the seven positions in the nonamer scaffold. This information can be used in
      attempts to develop optimized peptides and peptidomimetics that inhibit pilus
      assembly in pathogenic bacteria.

PMID- 15715465
TI  - Application of a flexible synthesis of (5R)-thiolactomycin to develop new
      inhibitors of type I fatty acid synthase.
AB  - Fatty acid synthase (FAS) catalyzes the synthesis of palmitate from the
      sequential condensation of an acetyl primer with two carbon units added from
      malonyl-CoA. Inhibition of the beta-ketoacyl synthase domain of mammalian FAS
      leads to selective cytotoxicity to various cancer cell lines in vitro and in
      vivo. Also, inhibitors of FAS can cause reduced food intake and body weight in
      mice. Naturally occurring thiolactomycin (TLM) was used as a template to develop
      a new class of type I FAS inhibitors. Using a flexible synthesis, families of TLM
      structural analogues were obtained that possess selective FAS activity and
      display anticancer and weight loss effects. Compounds 13a and 13d inhibit pure
      FAS (ZR-75-1 breast cancer, IC(50) = <or=20 microg/mL), are nontoxic (MCF-7,
      IC(50) = >50 microg/mL), and display effective weight loss in BalbC mice (>5%).
      Another subclass of TLM derivatives (23b-d, 31a) exhibits FAS activity (IC(50) =
      <or=15 microg/mL), causes weight loss (>5%), and is cytotoxic to cancer cells
      (IC(50) < 38 microg/mL). Finally, a third subclass (16b, 29, 30) is also active
      against FAS (IC(50) = <or=20 microg/mL), is cytotoxic to cancer cells (IC(50) <
      25 mg/mL), and does not cause weight loss in BalbC mice. These studies identify
      thiolactomycin as a promising template for the development of new selective
      cancer and obesity treatments.

PMID- 15715466
TI  - Comparison of automated docking programs as virtual screening tools.
AB  - The performance of several commercially available docking programs is compared in
      the context of virtual screening. Five different protein targets are used, each
      with several known ligands. The simulated screening deck comprised 1000 molecules
      from a cleansed version of the MDL drug data report and 49 known ligands. For
      many of the known ligands, crystal structures of the relevant protein-ligand
      complexes were available. We attempted to run experiments with each docking
      method that were as similar as possible. For a given docking method, hit rates
      were improved versus what would be expected for random selection for most protein
      targets. However, the ability to prioritize known ligands on the basis of docking
      poses that resemble known crystal structures is both method- and target
      dependent.

PMID- 15715467
TI  - Mechanism of cytotoxicity of copper(I) complexes of 1,2
      bis(diphenylphosphino)ethane.
AB  - The cytotoxic properties of arylphosphines are regulated by metals. We have
      synthesized a series of copper(I) complexes of 1,2-bis(diphenylphosphino)ethane
      (DPPE) and tested their in vitro cytotoxicity in a human lung carcinoma cell line
      H460. One of the complexes [Cu(2)(DPPE)(3)(CH(3)CN)(2)](ClO(4))(2) (C1), showed
      maximum cytotoxicity comparable to that of adriamycin. Treatment of cells with C1
      caused DNA damage in vitro and activated the p53 pathway. Flow cytometry revealed
      that growth inhibition by C1 was due to a combination of cell cycle arrest and
      apoptosis. Simultaneous addition of C1 and adriamycin increased the cytotoxicity
      of either compound, suggesting the potential use of adriamycin in combination
      with C1. DNA binding and simulation studies suggest that adriamycin binds to DNA
      synergistically in the presence of C1. Thus, we have identified C1, a copper(I)
      complex of DPPE, as a potential chemotherapeutic drug for further testing, which
      could be used either alone or in combination with other chemotherapeutic drugs.

PMID- 15715468
TI  - Novel anticholinesterases based on the molecular skeletons of furobenzofuran and
      methanobenzodioxepine.
AB  - Reductive cyclization of 5-hydroxy-3-methyl-3-methoxycarbonylmethylenebenzofuran
      2(3H)-one (4) gave 5-hydroxy-3a-methyl-2,3,3a,8a-tatrahydrofuro[2,3-b]benzofuran
      (5) and the rearrangement product 7-hydroxy-4,5-dihydro-2,5-methano-1,3
      benzodioxepine (6). Reaction of compounds 5 and 6 with different isocyanates
      provided two series novel carbamates (7-12) whose structures were confirmed by X
      ray crystallography. These were assessed for anticholinesterase action against
      freshly prepared human enzyme and proved to be potent inhibitors of either acetyl
      (AChE) or butyrylcholinesterase (BChE) with specific compounds exhibiting
      remarkable selectivity. Because the two series of carbamates (7-12) differ in
      their phenolic moieties, their respective potency and selectivity for AChE versus
      BChE was governed by their N-substituted groups. This same characteristic was
      also present in a series of physovenine analogues (1, 13, 15, 17) and
      physostigmine analogues (2, 14, 16, 18). These structure-activity relations
      proved valuable in elucidating the mechanisms underpinning the interaction
      between carbamate-based cholinesterase inhibitors and their enzyme target. In
      addition, because physostigmine analogues have demonstrated activity in lowering
      the Alzheimer's disease protein, amyloid precursor protein (APP), examples of the
      two new series of carbamates were characterized in culture assays of quantifying
      cell viability and synthesis of APP.

PMID- 15715469
TI  - CoMFA, synthesis, and pharmacological evaluation of (E)-3-(2-carboxy-2-arylvinyl)
      4,6-dichloro-1H-indole-2-carboxylic acids: 3-[2-(3-aminophenyl)-2-carboxyvinyl]
      4,6-dichloro-1H-indole-2-carboxylic acid, a potent selective glycine-site NMDA
      receptor antagonist.
AB  - (E)-3-(2-Carboxy-2-phenylvinyl)-4,6-dichloro-1H-indole-2-carboxylic acid, 1, is a
      potent and selective antagonist of the glycine site of the N-methyl-d-aspartate
      (NMDA) receptor. Using 3D comparative molecular field analysis (CoMFA) to guide
      the synthetic effort, a series of aryl diacid analogues of 1 were synthesized to
      optimize in vivo potency, duration of action, and binding activity. It was found
      that the incorporation of a substituted aromatic with an electron withdrawing
      group or a heterocyclic group at the 2-position of the 3-propenyl moiety of 1
      gave compounds with better affinity and potency in the murine stroke model.
      Ultimately this led to the discovery of 3-[2-(3-aminophenyl)-2-carboxyvinyl]-4,6
      dichloro-1H-indole-2-carboxylic acid, 19, as a new potent selective glycine-site
      NMDA receptor antagonist.

PMID- 15715470
TI  - Novel inhibitors of human histone deacetylases: design, synthesis, enzyme
      inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
AB  - To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of
      compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and
      synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is
      replaced by a thiol, was found to be as potent as SAHA, and optimization of this
      series led to the identification of HDAC inhibitors more potent than SAHA. In
      cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong
      activity, and its potency was comparable to that of SAHA. The cancer cell growth
      inhibitory activity was verified to be the result of histone hyperacetylation and
      subsequent induction of p21(WAF1/CIP1) by Western blot analysis. Kinetical enzyme
      assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis
      within the cell interacts with the zinc ion in the active site of HDACs.

PMID- 15715471
TI  - Synthesis and cellular studies of nonaggregated water-soluble phthalocyanines.
AB  - Water-soluble phthalocyanines are promising photosensitizers for application in
      cancer therapy and in the photoinactivation of viruses. The water-soluble
      zinc(II) phthalocyanines 5 and 6 were synthesized by converting the corresponding
      ester derivative 4 into the sodium carboxylate and carboxylic acid species.
      Compound 5 can be solubilized in water as a monomeric species, as demonstrated by
      UV/vis and fluorescence spectroscopy. These compounds were characterized by
      analytical and spectroscopic methods and, in the case of 4, by X-ray
      crystallography. The water-soluble phthalocyanines were found to have low dark
      cytotoxicity toward V79 hamster fibroblasts and human HEp2 cells, to be
      phototoxic at low light and drug doses, to be taken up by cells in culture, and
      to localize intracellularly, mainly in the cell lysosomes. Conjugation of the
      anionic phthalocyanines with positively charged LipoGen liposomes resulted in
      effective delivery of these compounds into the nuclei of cells. It is concluded
      that these highly water-soluble phthalocyanines are promising sensitizers for the
      photodynamic therapy of tumors.

PMID- 15715472
TI  - The role of intracellularly released formaldehyde and butyric acid in the
      anticancer activity of acyloxyalkyl esters.
AB  - Previous studies described a family of anticancer histone deacetylase inhibitor
      prodrugs of formula Me(CH(2))(2)COOCH(R)OR(1), which upon intracellular
      hydrolysis release acids and aldehydes. This study examines the mechanisms by
      which the prodrugs affect tumor cells and the contribution of the released
      aldehyde (formaldehyde or acetaldehyde) and acids to their anticancer activity.
      Type I prodrugs release 2 equiv of a carboxylic acid and 1 equiv of an aldehyde,
      and of Type II release 2 equiv of acids and 2 equiv of an aldehyde. SAR studied
      inhibition of proliferation, induction of differentiation and apoptosis, histone
      acetylation, and gene expression. Formaldehyde, measured intracellularly, was the
      dominant factor affecting proliferation and cell death. Among the released acids,
      butyric acid elicited the greatest antiproliferative activity, but the nature of
      the acid had minor impact on proliferation. In HL-60 cells, formaldehyde
      releasing prodrugs significantly increased apoptosis. The prodrugs affected to a
      similar extent the wild-type HL-60 and MES-SA cell lines and their multidrug
      resistant HL-60/MX2 and MES-Dx5 subclones. In a cell-free histone deacetylase
      (HDAC) inhibition-assay only butyric acid inhibited HDAC activity. The butyric
      acid and formaldehyde induced cell differentiation and increased p53 and p21
      levels, suggesting that both affect cancer cells, the acid by inhibiting HDAC and
      the aldehyde by an as yet unknown mechanism.

PMID- 15715473
TI  - Optimization and validation of a docking-scoring protocol; application to virtual
      screening for COX-2 inhibitors.
AB  - To exploit available structural information about the cyclooxygenase enzyme for
      the virtual screening of large chemical libraries, a docking-scoring protocol was
      tuned and validated. The screening accuracy was assessed using a series of known
      inhibitors and a set of diverse a priori inactive compounds that was seeded with
      known active ligands. The major parameters of the DOCK algorithm were
      investigated. A large improvement of the results was obtained on tweaking some of
      them. The generated complexes were rescored using six scoring functions. In this
      way, the striking importance of this step was demonstrated, as well as the good
      performances of DOCK energy and SCORE for this target. The results were further
      improved via a consensus approach. As a first application, a subset of a large
      compound library was screened using this protocol. Among the compounds that were
      selected for biological testing, a third of them turned out to have a significant
      enzyme inhibition.

PMID- 15715474
TI  - A new method for estimating the importance of hydrophobic groups in the binding
      site of a protein.
AB  - Interactions between the hydrophobic regions of a binding site and those of a
      complementary ligand are often observed to provide the driving force for binding.
      We present a new method for the analysis of hydrophobic regions in the binding
      site of a protein that considers not only atom type but also the nonadditive
      effects arising from the shape and extent of a nonpolar region. The method has
      been parametrized using a purpose-built genetic algorithm to optimize its ability
      to identify those regions that are more likely to form a strong interaction with
      a nonpolar ligand group. We demonstrate the ability of this method to account for
      changes in the shape and extent of the exposed nonpolar surface, using both
      artificial and protein examples. The method is also able to rationalize
      differences in binding affinity for ligand-protein complexes with largely
      hydrophobic binding sites.

PMID- 15715475
TI  - Extravascular transport of drugs in tumor tissue: effect of lipophilicity on
      diffusion of tirapazamine analogues in multicellular layer cultures.
AB  - The extravascular diffusion of antitumor agents is a key determinant of their
      therapeutic activity, but the relationships between physicochemical properties of
      drugs and their extravascular transport are poorly understood. It is well-known
      that drug lipophilicity plays an important role in transport across biological
      membranes, but the net effect of lipophilicity on transport through multiple
      layers of tumor cells is less clear. This study examines the influence of
      lipophilicity (measured as the octanol-water partition coefficient P) on the
      extravascular transport properties of the hypoxic cytotoxin tirapazamine (TPZ, 1)
      and a series of 13 neutral analogues, using multicellular layers (MCLs) of HT29
      human colon carcinoma cells as an in vitro model for the extravascular
      compartment of tumors. Flux of drugs across MCLs was determined using diffusion
      chambers, with the concentration-time profile on both sides of the MCL measured
      by HPLC. Diffusion coefficients in the MCLs (D(MCL)) were inversely proportional
      to M(r)(0.5) (M(r), relative molecular weight), although this was a minor
      contributor to differences between compounds over the narrow M(r) range
      investigated. Differences in lipophilicity had a larger effect, with a sigmoidal
      dependence of D(MCL) on log P. Correcting for M(r) differences, lipophilic
      compounds (log P > 1.5) had ca. 15-fold higher D(MCL) than hydrophilic compounds
      (log P < -1). Using a pharmacokinetic/pharmacodynamic (PK/PD) model in which
      diffusion in the extravascular compartment of tumors is considered explicitly, we
      demonstrated that hypoxic cell kill is very sensitive to changes in extravascular
      diffusion coefficient of TPZ analogues within this range. This study shows that
      simple monosubstitution of TPZ can alter log P enough to markedly improve
      extravascular transport and activity against target cells, especially if rates of
      metabolic activation are also optimized.

PMID- 15715476
TI  - Structure-based drug discovery using GPCR homology modeling: successful virtual
      screening for antagonists of the alpha1A adrenergic receptor.
AB  - In this paper, we describe homology modeling of the alpha1A receptor based on the
      X-ray structure of bovine rhodopsin. The protein model has been generated by
      applying ligand-supported homology modeling, using mutational and ligand SAR data
      to guide the protein modeling procedure. We performed a virtual screening of the
      company's compound collection to test how well this model is suited to identify
      alpha1A antagonists. We applied a hierarchical virtual screening procedure guided
      by 2D filters and three-dimensional pharmacophore models. The ca. 23,000 filtered
      compounds were docked into the alpha1A homology model with GOLD and scored with
      PMF. From the top-ranked compounds, 80 diverse compounds were tested in a
      radioligand displacement assay. 37 compounds revealed K(i) values better than 10
      microM; the most active compound binds with 1.4 nM to the alpha1A receptor. Our
      findings suggest that rhodopsin-based homology models may be used as the
      structural basis for GPCR lead finding and compound optimization.

PMID- 15715477
TI  - Synthesis and biological evaluation of dimeric RGD peptide-paclitaxel conjugate
      as a model for integrin-targeted drug delivery.
AB  - Targeting drugs to receptors involved in tumor angiogenesis is a novel and
      promising approach to improve cancer treatment. In this study, we evaluated the
      antitumor activity of paclitaxel (PTX) conjugated with a bicyclic peptide
      E[c(RGDyK)](2) (RGD) in a metastatic breast cancer cell line (MDA-MB-435). The
      cyclic RGD peptide selectively binds to alpha(v) integrin receptors that are
      highly expressed in metastatic cancer cells. PTX, an antimicrotubule agent, is a
      potent antitumor agent commonly used in the treatment of advanced metastatic
      breast cancer. The in vitro results showed that RGD peptide inhibited cell cycle
      proliferation by arresting cells in G(0)/G(1)-phase. The PTX-RGD conjugate
      inhibited cell proliferation with activity comparable to that observed for
      paclitaxel, both of which were mediated by an arrest of G(2)/M-phase of the cell
      cycle followed by apoptosis. Although the PTX-RGD conjugate showed slightly
      decreased integrin binding affinity than the unconjugated peptide, it indicated
      integrin specific accumulation in vivo. (125)I-Labeled PTX-RGD showed highest
      tumor uptake at 2 h postinjection (2.72 +/-0.16%ID/g) and best tumor/background
      contrast after 4 h postinjection. Our results demonstrate the potential of tumor
      targeted delivery of paclitaxel based on the specific recognition of cell
      adhesion molecule alpha(v)beta(3) integrin to reduce toxicity and enhance
      selective killing of cancer cells.

PMID- 15715478
TI  - Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as
      orally active, irreversible inhibitors of human epidermal growth factor receptor
      2 kinase activity.
AB  - A series of new 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitrile
      derivatives that function as irreversible inhibitors of human epidermal growth
      factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) kinases
      have been prepared. These compounds demonstrated enhanced activities for
      inhibiting HER-2 kinase and the growth of HER-2 positive cells compared to our
      EGFR kinase inhibitor 86 (EKB-569). Three synthetic routes were used to prepare
      these compounds. They were prepared mostly by acylation of 6-amino-4
      (arylamino)quinoline-3-carbonitriles with unsaturated acid chlorides or by
      amination of 4-chloro-6-(crotonamido)quinoline-3-carbonitriles with monocyclic or
      bicyclic anilines. The third route was developed to prepare a key intermediate, 6
      acetamido-4-chloroquinoline-3-carbonitrile, that involved a safer cyclization
      step. We show that attaching a large lipophilic group at the para position of the
      4-(arylamino) ring results in improved potency for inhibiting HER-2 kinase. We
      also show the importance of a basic dialkylamino group at the end of the Michael
      acceptor for activity, due to intramolecular catalysis of the Michael addition.
      This, along with improved water solubility, resulted in compounds with enhanced
      biological properties. We present molecular modeling results consistent with the
      proposed mechanism of inhibition. Binding studies of one compound, 25o (C-14
      radiolabeled), showed that it binds irreversibly to HER-2 protein in BT474 cells.
      Furthermore, it demonstrated excellent oral activity, especially in HER-2
      overexpressing xenografts. Compound 25o (HKI-272) was selected for further
      studies and is currently in phase I clinical trials for the treatment of cancer.

PMID- 15715480
TI  - Synthesis and biological evaluation of a new series of 2,3,5-substituted [1,2,4]
      thiadiazoles as modulators of adenosine A1 receptors and their molecular
      mechanism of action.
AB  - We synthesized two series (7a-i and 8a-i) of 2,3,5-substituted [1,2,4]
      thiadiazole analogues of SCH-202676 (7a, 2,3-diphenyl-5-N-methylimino-2H-[1,2,4]
      thiadiazole) with emphasis on the N-imino substituent. Compounds 7a-g,i and 8a-g
      at a final concentration of 1 microM significantly inhibited [(3)H]CCPA (2-chloro
      N(6)- cyclopentyladenosine) agonist binding to human A(1) adenosine receptors. At
      the same concentration, all compounds appeared to increase [(3)H]DPCPX (1,3
      dipropyl-8-cyclopentylxanthine) antagonist binding. Compound 7a and LUF5855 (7g)
      were selected for further characterization and studied in both equilibrium and
      kinetic radioligand binding experiments. The results suggest a nonstoichiometric
      interaction with the receptor. Further bioanalytical procedures (HPLC and MS)
      provided proof for an unusual receptor interaction in which 7a and 7g upon
      incubation were transformed into their corresponding thioureas 5a and 5g. We
      suggest that the thiadiazoles are sulfhydryl modifying agents rather than
      allosteric modulators, as they appear to reversibly modify the sulfhydryl groups
      of cysteine residues in cell membrane preparations.

PMID- 15715479
TI  - Indazole estrogens: highly selective ligands for the estrogen receptor beta.
AB  - The estrogen receptors, ERalpha and ERbeta, are important pharmaceutical targets.
      To develop ERbeta-selective ligands, we synthesized a series of nonsteroidal
      compounds having a phenyl-2H-indazole core with different groups at C-3. Several
      of these show high affinity and good ERbetaselectivity, especially those with
      polar and/or polarizable substituents at this site (halogen, CF(3), nitrile); the
      best compounds have affinities for ERbeta comparable to estradiol, with
      ERbetaaffinity selectivity >100. This potency and ERbeta selectivity is also seen
      in cell-based transcriptional assays, where several compounds showed ERbeta
      efficacies equivalent to that of estradiol with ERbeta potency selectivities of
      100. These compounds might prove useful as selective pharmacological probes to
      study the biological actions of estrogens mediated through ERbeta, and they might
      lead to the development of useful pharmaceuticals. These findings also contribute
      to an evolving pharmacophore that characterizes certain nonsteroidal ligands
      having high ERbeta subtype affinity and potency selectivity.

PMID- 15715481
TI  - Synthesis and cytotoxic evaluation of novel spirohydantoin derivatives of the
      dihydrothieno[2,3-b]naphtho-4,9-dione system.
AB  - The synthesis and cytotoxic evaluation of 3-(alkyl)(alkyl
      substituted)spiro[(dihydroimidazo-2,4-dione)-5,3'-(2',3'-dihydrothieno[2,3
      b]naphtho-4',9'-dione)]derivatives are described. Evaluation of these analogues
      against the MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell
      lines uncovered for most of the compounds a cytotoxic potency comparable to or
      greater than that of doxorubicin. Compound 15 exhibited remarkable cytotoxic
      activity against several other human solid tumor cell lines. Interestingly, only
      a partial cross-resistance to compound 15 in selected tumor cell sublines known
      to be resistant to doxorubicin (MCF-7/Dx and A2780/Dx) was observed, whereas a
      total absence of cross-resistance in a tumor cell subline selected for resistance
      to cisplatin was found (A2780/DDP).

PMID- 15715482
TI  - Novel [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3'-spiro-5''
      (4''-amino-1'',2''-oxathiole-2'',2" -dioxide) derivatives with anti-HIV-1 and
      anti-human-cytomegalovirus activity.
AB  - New [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-d-ribofuranosyl]-3'-spiro-5' '
      (4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives substituted at
      the 4' '-amino group of the spiro moiety with different carbonyl functionalities
      have been designed and synthesized. Various synthetic procedures, on the scarcely
      studied reactivity of the 3'-spiroaminooxathioledioxide moiety, have been
      explored. The compounds were evaluated for their inhibitory effect on both wild
      type and TSAO-resistant HIV-1 strains, in cell culture. The presence of a methyl
      ester (10) or amide groups (12) at the 4''-position conferred the highest anti
      HIV-1 activity, while the free oxalyl acid derivative (11) was 10- to 20-fold
      less active against the virus. In contrast, the presence at this position of
      (un)substituted ureido or acyl groups markedly diminished or annihilated the anti
      HIV-1 activity. Surprisingly, some of the target compounds also showed inhibition
      of human cytomegalovirus (HCMV) replication at subtoxic concentrations. This has
      never been observed previously for TSAO derivatives. In particular, compound 26
      represents the first TSAO derivative with dual anti-HIV-1 and -HCMV activity.

PMID- 15715483
TI  - 3-[(2R)-Amino-2-phenylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-
      6-methylpyrimidin-2,4-dione (NBI 42902) as a potent and orally active antagonist
      of the human gonadotropin-releasing hormone receptor. Design, synthesis, and in
      vitro and in vivo characterization.
AB  - Further structure-activity relationship studies of a series of substituted
      uracils at the 1, 3, and 5 positions resulted in the discovery of several potent
      antagonists of the human gonadotropin-releasing hormone receptor. Uracils bearing
      a side chain derived from phenylglycinol at the 3-position were shown to be
      orally bioavailable in monkeys. 3-[(2R)-Amino-2-phenylethyl]-1-(2,6
      difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methylpyrimidin-2,4-dione (R-13b,
      NBI 42902) displayed subnanomolar binding affinity (K(i) = 0.56 nM) and was a
      potent functional antagonist (IC(50) = 3.0 nM in Ca(2+) flux assay) at the human
      GnRH receptor. It also bound to the monkey GnRH receptor with high affinity (K(i)
      = 3.9 nM). In addition, R-13bhad good plasma exposure in cynomolgus monkeys after
      oral administration, with a C(max) of 737 ng/mL and an AUC of 2392 ng/mL.h at a
      10 mg/kg dose. Moreover, oral administration of R-13b to castrated male
      cynomolgus monkeys resulted in a significant decrease in serum levels of
      luteinizing hormone. These results demonstrate that compounds from this series of
      uracils are potent GnRH antagonists with good oral bioavailability and efficacy
      in nonhuman primates.

PMID- 15715484
TI  - Modulation of MRP-1-mediated multidrug resistance by indomethacin analogues.
AB  - Multidrug resistance (MDR) is a major limiting factor in the development and
      application of drug candidates. MDR caused by MRP-1 is known to be modulated by
      the nonsteroidal antiinflammatory drug indomethacin. We have synthesized and
      biologically evaluated a library of indomethacin analogues. The indomethacin
      derived compound library was synthesized employing the Fischer-indole synthesis
      as the key transformation and making use of a "resin-capture-release" strategy.
      Sixty representative members of the library were evaluated in a cell biological
      cytotoxicity assay employing the MRP-1 expressing human glioblastoma cell line
      T98G as a model system. Nine of the 60 tested derivatives increased the
      doxorubicin-mediated cytotoxicity at a comparable or higher level than
      indomethacin itself. Analysis of these derivatives revealed an interesting
      structure-function relationship. Most remarkably, two substances increased the
      toxicity, when doxorubicin was used at clinically relevant low concentrations, at
      a higher degree than indomethacin.

PMID- 15715485
TI  - Synthesis and biological evaluation of neutral and zwitterionic 3-carboranyl
      thymidine analogues for boron neutron capture therapy.
AB  - Novel 3-carboranyl thymidine analogues (3CTAs) were synthesized as potential
      boron delivery agents for boron neutron capture therapy (BNCT). This library
      includes six zwitterionic NH(3)(+)-nido-m-carborane-substituted thymidine
      analogues (Thds) and the corresponding neutral NH(2)-closo-m-carborane
      substituted counterparts. All compounds of this library were good substrates for
      recombinant human thymidine kinase 1 (TK1) with phosphorylation rates up to 89%
      relative to that of Thd. One compound out of this library, 3-[3-(7-NH(3)(+)-nido
      m-carboran-1-yl)propan-1-yl]thymidine (19b), showed selective retention in TK1
      expressing murine L929 wild-type tumors versus L929 TK1 (-) tumors in
      biodistribution studies. The biological evaluation of the zwitterionic NH(3)(+)
      nido-m-carborane-substituted Thds indicated improved aqueous solubility and
      similar or even superior potential as BNCT agents compared with different classes
      of 3CTAs (Cancer Res. 2004, 64, 6280-6286 and 6287-6295). To complete previous
      structure-activity relationship (SAR) studies, 3-[(closo-o
      carboranyl)methyl]thymidine (4) was also synthesized and evaluated.

PMID- 15715486
TI  - Synthesis and evaluation of S-acyl-2-thioethyl esters of modified nucleoside 5'
      monophosphates as inhibitors of hepatitis C virus RNA replication.
AB  - Several triphosphates of modified nucleosides (1-6) were identified as inhibitors
      (IC(50) = 0.08-3.8 microM) of hepatitis C virus RNA-dependent RNA polymerase
      (RdRp). Although the initial SAR developed by determining the ability of the
      triphosphates to inhibit the in vitro activity of the HCV RdRp identified several
      potent inhibitors, none of the corresponding nucleosides exhibited significant
      inhibitory potency in a cell-based replicon assay. To improve upon the activity,
      bis(tBu-S-acyl-2-thioethyl) nucleoside 5'-monophosphate esters (7-12) were
      synthesized, and these derivatives exhibited improved potency compared to the
      corresponding nucleosides in the cell-based assay. Analysis of the intracellular
      metabolism demonstrated that the S-acyl-2-thioethyl (SATE) prodrug is metabolized
      to the 5'-triphosphate 40- to 155-fold more efficiently compared to the
      corresponding nucleoside. The prodrug approach involving bis(tBuSATE)cytidine 5'
      monophosphate ester significantly reduced the deamination of cytidine derivatives
      by cellular deaminases. Additionally, chromosomal aberration studies with the
      SATE prodrug in cells showed no statistically relevant increase in aberrations
      compared to the concurrent controls.

PMID- 15715487
TI  - Synthesis and evaluation of double-prodrugs against HIV. Conjugation of D4T with
      6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, emivirine)-type reverse
      transcriptase inhibitors via the SATE prodrug approach.
AB  - This paper reports the synthesis and the antiviral activities of new double
      prodrugs against HIV based on the known mixed SATE (S-acyl-2-thioethyl) prodrug
      approach. The monophosphate of the nucleoside reverse transcriptase inhibitor
      (NRTI) d4T was masked with one SATE group and one aromatic group through which a
      nonnucleoside reverse transcriptase inhibitor (NNRTI) was linked. Double-prodrug
      1 was a hybrid between d4T monophosphate and the known NNRTI MKC-442, which were
      linked through a labile p-hydroxybenzoyl protection group in the N-3 position of
      MKC-442. Double-prodrugs 2 and 3 were conjugates between d4T monophosphate and
      the new NNRTIs 15 and 19 linked through a stable phenolic linker that was a part
      of the N-1 substituents of the NNRTIs. The double-prodrugs 1, 2, and 3 all had
      good activities against wild-type HIV-1, Y181C mutant, and also against a HIV-2
      strain that was resistant to NNRTIs.

PMID- 15715488
TI  - Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive
      properties of 3'-substituted deschloroepibatidine analogues. Novel nicotinic
      antagonists.
AB  - A series of 3'-substituted deschloroepibatidine analogues (3a-g and 4) showed
      high affinity for alpha4beta2 binding and relatively weak affinity for alpha7
      nAChRs. The 3'-ethynyl (3g) and 3'-fluoro (3a) analogues with K(i) values of 0.02
      and 0.037 nM, respectively, were the most potent. Even though the alpha4beta2
      binding affinity of several of the analogues were equal to that of epibatidine,
      all of the compounds were weak agonists in the antinociceptive, hypothermia, and
      spontaneous activity test in mice. In contrast, all of the compounds were
      functional antagonists of nicotine-induced antinociception. In general, compounds
      3a-g and 4 were more potent in the tail-flick assay than the hot-plate test. For
      example, the 3'-fluoro analogue 3a and the N-methyl-3'-iodo analogue 4 showed
      AD(50) values of 0.07 and 0.04 microg/kg, respectively, in the tail flick test
      and only 35 and 0% inhibition at 20 and 10 microg/kg in the hot-plate assay,
      respectively. These results suggest that these compounds will be highly useful
      for identifying which specific receptor subtypes are involved in each of
      nicotine's pharmacological effects. The high affinity of the N-methyl-3'-iodo
      analogue 4 combined with its weak agonist and potent antagonist activity suggests
      that carbon-11 and iodine-123 analogues may be useful as PET and SPECT ligands,
      respectively, for studying nAChRs in vivo.

PMID- 15715489
TI  - Chiral DNA gyrase inhibitors. 3. Probing the chiral preference of the active site
      of DNA gyrase. Synthesis of 10-fluoro-6-methyl-6,7-dihydro-9-piperazinyl- 2H
      benzo[a]quinolizin-20-one-3-carboxylic acid analogues.
AB  - In pursuit of an apparent literature anomaly, S- and R-6-methyl-6,7-dihydro-2H
      benzo[a]quinolizin-2-one-3-carboxylic acids (12 and 22) were synthesized by an
      unambiguous route from optically active norephedrines, and their antibacterial
      potencies were measured. Against Gram-negative microorganisms and DNA gyrase a
      preference for S-absolute configuration was found whereas R-absolute
      stereochemistry was more active against Gram-positives. These results are in
      partial conflict with an earlier report. In an attempt to enhance potency,
      racemic 10-fluoro-9-piperazinyl (35) and related analogues were synthesized by a
      novel route. The latter analogues were surprisingly unimproved in potency. The
      implications of these findings are briefly discussed.

PMID- 15715490
TI  - 8-Substituted analogues of 3-(3-cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl
      adenine: highly potent and selective PDE4 inhibitors.
AB  - 3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been
      identified as a lead structure, which selectively inhibits human lung PDE4 (436
      nM) and is also active in a number of in vitro and in vivo models of
      inflammation. Here we describe the synthesis and pharmacology of a series of
      highly potent 8-[(benzyloxy)methyl]-substituted analogues, with potencies in the
      range 10-300 nM. In addition, several compounds showed interesting PDE4 subtype
      specificities, for example, the 3-thienyl derivative 5v, which showed 6-10 nM
      potency at PDE4B, D3, and D5 and a 20- to 200-fold selectivity over A and D2,
      respectively.

PMID- 15715491
TI  - Degradation, insulin secretion, and antihyperglycemic actions of two palmitate
      derivitized N-terminal pyroglutamyl analogues of glucose-dependent insulinotropic
      polypeptide.
AB  - Exploitation of glucose-dependent insulinotropic polypeptide (GIP) is hindered by
      its short biological half-life and rapid renal clearance. To circumvent these
      problems, two novel acylated N-terminally modified GIP analogues, N
      pGluGIP(LysPAL(16)) and N-pGluGIP(LysPAL(37)), were evaluated. In contrast to
      native GIP, both analogues were completely resistant to dipeptidyl peptidase IV
      degradation. In GIP-receptor transfected fibroblasts, N-pGluGIP(LysPAL(16)) and N
      pGluGIP(LysPAL(37)) exhibited enhanced stimulation of cAMP production.
      Insulinotropic responses in clonal beta-cells were similar to native GIP. When
      administered together with glucose to ob/ob mice, the glycemic excursions were
      significantly less for both analogues and insulin responses were greater than
      native GIP. Extended insulinotropic and antihyperglycemic actions were also
      evident. These data indicate that palmitate-derivitized analogues of N-terminal
      pyroglutamyl GIP represent a novel class of stable, long-acting, and effective
      GIP analogues for potential type 2 diabetes therapy.

PMID- 15715492
TI  - Synthesis of (+/-)-2-O-[4'-(N-9''-purinyl)butyl] myo-inositol 1,4,5
      tris(phosphate), a potent full agonist at the D-myo-inositol 1,4,5
      tris(phosphate) receptor.
AB  - Racemic 2-O-[4'(9''-N-purinyl)butyl] myo-inositol 1,4,5-tris(phosphate) 8 was
      synthesized starting from myo-inositol. Substitution of position 2 by an alkyl
      side chain was rendered possible by inversion of the chair conformation of the
      inositol ring by means of an orthoester. The final compound is a full agonist
      with the same order of potency as d-myo-inositol 1,4,5-tris(phosphate).

PMID- 15715493
TI  - Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus.
AB  - Glycyrrhizin (GL) was shown to inhibit SARS-coronavirus (SARS-CoV) replication in
      vitro. Here the anti-SARS-CoV activity of 15 GL derivatives was tested. The
      introduction of 2-acetamido-beta-d-glucopyranosylamine into the glycoside chain
      of GL resulted in 10-fold increased anti-SARS-CoV activity compared to GL. Amides
      of GL and conjugates of GL with two amino acid residues and a free 30-COOH
      function presented up to 70-fold increased activity against SARS-CoV but also
      increased cytotoxicity resulting in decreased selectivity index.

PMID- 15715494
TI  - New potential antihistaminic compounds. Virtual combinatorial chemistry,
      computational screening, real synthesis, and pharmacological evaluation.
AB  - To study the utility of the virtual combinatorial chemistry coupled with
      computational screening, a library of amine and urea derivatives was designed by
      virtual combinatorial synthesis and eventually computationally screened by a
      mathematical topological model as antihistaminic compounds. The results reveal
      that virtual combinatorial synthesis and virtual screening together with
      molecular topology are a powerful tool in the design of new drugs.

PMID- 15715495
TI  - Identification from a positional scanning peptoid library of in vivo active
      compounds that neutralize bacterial endotoxins.
AB  - Two peptoids that neutralize the Gram-negative lipopolysaccharide (LPS) were
      identified from the screening of a positional scanning library. The evaluation of
      the in vivo activity of these compounds in an endoxemia murine model is also
      reported. These peptoids did not neutralize lipid A, i.e., the hydrophobic toxic
      component of LPS. This fact suggests that they do not have access to the micellar
      core and that they should bind to the hydrophilic carbohydrate portion of LPS.

PMID- 15715496
TI  - Antithrombin activation by nonsulfated, non-polysaccharide organic polymer.
AB  - Accelerated antithrombin inhibition of procoagulant enzymes has been exclusively
      achieved with polysulfated polysaccharides. We reasoned that antithrombin
      activation should be possible with nonsulfated activators based only on
      carboxylic acid groups. As a proof of the principle, linear poly(acrylic acid)s
      were found to bind to antithrombin and accelerate inhibition of factor Xa and
      thrombin. Our work demonstrates that molecules completely devoid of sulfate
      groups can activate antithrombin effectively and, more importantly, suggests that
      it may be possible to develop orally bioavailable, carboxylate-based antithrombin
      activators.

PMID- 15715497
TI  - Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1-(beta-D
      ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter.
AB  - Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(beta-d
      ribofuranosyl)benzimidazole (BDCRB) were synthesized and evaluated for their
      affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of
      competitive inhibition of [(3)H]glycylsarcosine (Gly-Sar) uptake in HeLa/hPEPT1
      cells by the amino acid ester prodrugs of BDCRB suggested their 2- to 4-fold
      higher affinity for hPEPT1 compared to BDCRB. Further, promoieties with
      hydrophobic side chains and l-configuration were preferred by the hPEPT1
      transporter.

PMID- 15715498
TI  - CH...O and CH...N hydrogen bonds in ligand design: a novel quinazolin-4-ylthiazol
      2-ylamine protein kinase inhibitor.
AB  - Aryl CH hydrogen bonds play an important role in the binding of several analogues
      of a pyrazol-3-ylquinazolin-4-ylamine inhibitor of glycogen synthase kinase 3
      (GSK3). Understanding the importance of these CH...O and CH...N hydrogen bonds
      allowed the design of a novel quinazolin-4-ylthiazol-2-ylamine inhibitor of GSK3
      with a structurally confirmed CH...O hydrogen bond to the protein.

PMID- 15715499
TI  - Novel 2-alkylamino-1,4-benzoxazine derivatives as potent neuroprotective agents:
      structure-activity relationship studies.
AB  - 2-Alkylamino-substituted-1,4-benzoxazine derivatives, a new class of potential
      neuroprotective agents, were synthesized and examined for their intrinsic
      cytotoxicity and their capacity to inhibit oxidative stress-mediated neuronal
      degeneration in vitro. Through structure-activity relationship studies, the 3,3
      diphenyl-substituted-1,4-benzoxazine derivative 3l was identified as the optimal
      candidate, owing to its potent neuroprotective activity, without the
      manifestation of intrinsic cytotoxicity. Accordingly, 3l proved to be effective
      in an animal model of excitotoxic lesions in newborn mice.

PMID- 15715500
TI  - Greater than the sum of its parts: combining models for useful ADMET prediction.
AB  - In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity)
      models are important tools in combating late-stage attrition in the drug
      discovery process. This work shows how ADMET models can be combined to tailor
      predictions depending on one's needs. We demonstrate how the judicious use of
      data and considered combination of predictions can produce models that provide
      truly useful answers. This approach is illustrated with the prediction of hERG
      channel blocking and cytochrome P450 2D6 inhibition, where combination of two
      predictive models (with >80% of compounds correctly predicted) resulted in models
      with even better predictive values (with >90% of compounds correctly predicted
      for those classes of interest).

PMID- 15715501
TI  - Synthesis, antitumor evaluation, and apoptosis-inducing activity of hydroxylated
      (E)-stilbenes.
AB  - The parallel solution-phase synthesis of a series of 30 monohydroxylated (E)
      stilbene analogues is described. In vitro screening revealed low micromolar
      activity (GI(50)) against the MDA MB 468 breast cancer cell line. Activity in MDA
      MB 468 cells correlated with the ability to induce apoptosis following drug
      treatment by the most potent agents in the series, e.g., 5dy and 5jy, an
      observation further reinforced by AnnexinV-FITC analysis and fluorescence
      microscopy.

PMID- 15715502
TI  - Therapy considerations in drug-eluting stents.
AB  - Approximately 12 million Americans have coronary artery disease, and almost one
      in five deaths in the United States can be attributed to this disease. In
      addition, 1.2 million Americans undergo cardiac catheterization and over one-half
      million receive a percutaneous coronary intervention such as balloon angioplasty,
      atherectomy, or stent implantation annually. This article will provide an
      overview of (1) atherosclerosis, the progressive disease which can lead to
      thrombotic events and/or the development of hemodynamically significant coronary
      artery lesions; (2) restenosis, the reappearance of significant lesions after
      coronary interventions such as stent placement; and (3) drug-eluting stents, the
      devices which, by using appropriate polymers to elute the appropriate drug with
      the appropriate pharmacokinetics, have almost completely eliminated restenosis.

PMID- 15715503
TI  - Optimizing drug delivery systems using systematic "design of experiments." Part
      I: fundamental aspects.
AB  - Design of an impeccable drug delivery product normally encompasses multiple
      objectives. For decades, this task has been attempted through trial and error,
      supplemented with the previous experience, knowledge, and wisdom of the
      formulator. Optimization of a pharmaceutical formulation or process using this
      traditional approach involves changing one variable at a time. Using this
      methodology, the solution of a specific problematic formulation characteristic
      can certainly be achieved, but attainment of the true optimal composition is
      never guaranteed. And for improvement in one characteristic, one has to trade off
      for degeneration in another. This customary approach of developing a drug product
      or process has been proved to be not only uneconomical in terms of time, money,
      and effort, but also unfavorable to fix errors, unpredictable, and at times even
      unsuccessful. On the other hand, the modern formulation optimization approaches,
      employing systematic Design of Experiments (DoE), are extensively practiced in
      the development of diverse kinds of drug delivery devices to improve such
      irregularities. Such systematic approaches are far more advantageous, because
      they require fewer experiments to achieve an optimum formulation, make problem
      tracing and rectification quite easier, reveal drug/polymer interactions,
      simulate the product performance, and comprehend the process to assist in better
      formulation development and subsequent scale-up. Optimization techniques using
      DoE represent effective and cost-effective analytical tools to yield the "best
      solution" to a particular "problem." Through quantification of drug delivery
      systems, these approaches provide a depth of understanding as well as an ability
      to explore and defend ranges for formulation factors, where experimentation is
      completed before optimization is attempted. The key elements of a DoE
      optimization methodology encompass planning the study objectives, screening of
      influential variables, experimental designs, postulation of mathematical models
      for various chosen response characteristics, fitting experimental data into these
      model(s), mapping and generating graphic outcomes, and design validation using
      model-based response surface methodology. The broad topic of DoE optimization
      methodology is covered in two parts. Part I of the review attempts to provide
      thought-through and thorough information on diverse DoE aspects organized in a
      seven-step sequence. Besides dealing with basic DoE terminology for the novice,
      the article covers the niceties of several important experimental designs,
      mathematical models, and optimum search techniques using numeric and graphical
      methods, with special emphasis on computer-based approaches, artificial neural
      networks, and judicious selection of designs and models.

PMID- 15715505
TI  - Cell membrane-associated MT1-MMP-dependent activation of pro-MMP-2 in A375
      melanoma cells.
AB  - Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, can
      degrade extracellular matrix components under physiological conditions and during
      cancer invasion and metastasis. Among the MMPs, the 72 kDa type IV collagenase
      MMP-2 (gelatinase A) is activated in a membrane-associated manner by an
      activation complex composed of membrane type 1 matrix metalloproteinase (MT1
      MMP), tissue inhibitor of matrixmetalloproteinase-2 (TIMP-2), and pro-MMP-2 in
      the presence of alphavbeta3 integrin receptor. The activation of pro-MMP-2
      correlates with increased occurrence of metastases. Increased MMP-2 activity has
      been demonstrated in many human tumors. In the present communication, we studied
      cell surface-associated activation of MMP-2 (72 kDa collagenase type IV) in the
      moderately metastatic human melanoma cell line A375. RESULTS: Activation of
      purified 72 kDa collagenase type IV, pro-MMP-2 from cervical cancer tissue
      homogenate and from serum-free culture medium of HT1080 cells grown in presence
      of concanavalin A, by A375 cells, was shown by gelatin zymography. A375 cells
      activated only pro-MMP-2 from purified MMP-9/MMP-2 mixture indicating that the
      activation is specific for MMP-2. Activation of MMP-2 and purified collagenase
      type IV by A375 membrane fraction and membrane extract was also demonstrated by
      gelatin zymography. When A375 cells were first incubated with anti-MT1-MMP
      polyclonal antibody, activation of collagenase type IV was significantly
      decreased, indicating that membrane-associated MMP-2 activation is MT1-MMP
      mediated. Immunocytochemistry showed MT1-MMP localization at focal adhesion
      sites. The presence of the components of activation complex-MT1-MMP and integrin
      alphavbeta3-were confirmed by Western blot, cell adhesion assay, and integrin
      subunit assay. CONCLUSION: Our experimental findings furnish another example of
      the unique membrane-associated MMP-2 activation mechanism in A375 melanoma cells
      and clearly indicate the role of MT1-MMP in MMP-2 activation. The information
      could help in developing new therapies designed to interfere with MMP activation
      and management of cancer and metastases.

PMID- 15715506
TI  - Alterations in bronchoalveolar lavage constituents, oxidant/antioxidant status,
      and lung histology following intratracheal instillation of respirable suspended
      particulate matter.
AB  - Urban suspended particulate pollutants differ with place of occurrence,
      meteorological conditions, physicochemical compositions, and the response of the
      bronchopulmonary apparatus. Lung injury following intratracheal instillation of
      respirable suspended particulate matter (RSPM) collected in an urban setting in
      India was investigated in rats. The animals were killed 15 days after exposure to
      2.5, 5.0, and 10.0 mg of RSPM. We examined the changes in lung histology,
      enzymatic activity in the bronchoalveolar lavage (BAL), and the oxidant/
      antioxidant status in lung homogenates. The alterations in these parameters were
      compared with those in rats instilled with quartz particulates, which were used
      as positive controls. Exposure to RSPM resulted in an increase in the relative
      weight of lungs and inflammatory changes evidenced by an increase in the total
      cellularity of the lungs, predominantly polymorphonuclear cells, demonstrable
      both in the lungs sections and in the bronchoalveolar lavage of the exposed
      animals. An increase in the protein content and in the lactate dehydrogenase
      activity in the BAL was found in the RSPM-exposed rats. A marked increase in the
      output of lipid peroxides and a dose-dependent increase in the formation of
      reactive nitrogen species (NO) in lung homogenates and BAL, respectively, was
      found in the RSPM-exposed rats. A significant decrease in the enzymatic lung
      antioxidants, superoxide dismutase, and catalase was observed. However, the
      alterations in the levels of glutathione in the lungs of the RSPM-exposed animals
      were not significant. The inflammatory reaction, oxidative changes, and enzyme
      release, were more marked in quartz-exposed animals in comparison to the RSPM
      exposed rats.

PMID- 15715507
TI  - Cell cycle regulators modulating con A mitogenesis and apoptosis in low-dose
      radiation-exposed mice.
AB  - Low doses of ionizing radiation (LDR) are reported to induce transient changes in
      mouse lymphocytes, such as enhanced response to polyclonal T cell mitogens,
      increased expression of heat shock proteins, and p53. We evaluated the role of
      cell cycle proteins and apoptosis in lymphocytes of C57BL/6 mice exposed to 20
      cGy fractionated LDR. We found an enhanced cell proliferation in response to the
      mitogen concanavalin A (con A). The expression of several cell cycle and
      apoptosis-related intracellular and extracellular proteins was analyzed by
      flowcytometry following labeling with specific antibodies. An increased response
      to con A was accompanied by an increase in the expression of proliferating cell
      nuclear antigen (PCNA) and cyclins D and A. The expression of cyclin B did not
      change significantly. In 20 cGy-exposed C57BL/6 mice, the caspase activity and
      apoptosis were reduced in con A-stimulated spleen cells as compared to sham
      controls. The expression of Fas and Fas ligand was analyzed by labeling with
      specific antibodies followed by flowcytometry. There was no change in the
      expression of Fas and Fas ligand. The change in the mitochondrial transmembrane
      potential was followed by labeling the cells with the dye 5,5',6,6',-tetrachloro
      1,1,3,3-tetraethylbenzimidazolcarbocyanine iodide (JC-I) and analyzing by
      flowcytometry. Mitochondrial stability was increased in spleen cells of LDR
      treated mice. These data suggest that LDR induces augmentation of mitogenic
      response by modulation of expression of cyclins and the mitochondrial membrane
      potential leading to reduced apoptosis.

PMID- 15715508
TI  - Arsenic-induced micronuclei formation in mammalian cells and its counteraction by
      tea.
AB  - The Gangetic plain of West Bengal, India, has been engulfed by a disastrous
      environmental calamity of arsenic contamination of the ground water. Chronic
      arsenic toxicity caused by drinking arsenic-contaminated water has been one of
      the worst health hazards gradually affecting nine districts of West Bengal since
      the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning
      sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung
      disease, gangrene of the toes, neuropathy, and skin cancer are other
      manifestations. Induction of cancer is frequently associated with DNA damage,
      changes in ploidy of cells, and non-random chromosome aberrations. Counteraction
      of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols
      could be a useful strategy to combat arsenic-induced DNA damage and thereby
      cancer. A review of the literature showed that it is the antioxidant property of
      tea polyphenols that affords protection against various types of cancer. The
      present study was conducted to investigate whether the extracts of green tea and
      black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate
      this arsenic-induced genotoxicity. The normal mammalian cell culture derived from
      male Chinese hamster lung fibroblast cells (V79) was used as the test system to
      assess the genotoxicity by micronucleus assay. The results showed that both green
      tea and black tea extracts have equal potential in modulating the arsenic-induced
      genotoxicity. This effect was perhaps induced by the constituent polyphenols
      present in green and black tea. In addition, the repair activity of the damaged
      cells was enhanced when treated with these tea extracts and their polyphenols.
      Thus, tea and its polyphenols may have a promising role in counteracting the
      devastating effects of arsenic.

PMID- 15715509
TI  - Aniline derivative-induced methemoglobin in rats.
AB  - Methemoglobinemia and hemolysis are the most prominent side-effects of exposure
      to a wide variety of arylamine drugs, including agricultural and industrial
      chemicals. Recent studies with aniline and dapsone have identified N-hydroxyl
      metabolites as the red blood cell (RBC) mediators. This study examines the time
      course methemoglobinemic potential of several halogenated aniline
      phenylhydroxylamines. Symptoms of aniline poisoning include headache, fatigue,
      dizziness, respiratory and cardiac arrest, and possibly death. Initial studies
      indicated that the parent compounds are converted to their toxic metabolites (N
      hydroxylamine), which enter the RBC and react with oxyhemoglobin. Consequent
      reduction of molecular oxygen to active oxygen species occurs, leading to RBC
      damage. Our laboratory is investigating the role of redox cycling and an
      alternative hypothesis--that a "hydroxylamine-centered" radical formed during
      arylhydroxylamine-oxyhemoglobin reaction results in RBC injury. The
      methemoglobinemic capacities of several structurally related N-hydroxy
      derivatives of aniline--phenylhydroxylamine (PHA), p-fluoro-, p-chloro-, p-bromo
      , and p-iodo-PHA--were studied spectrophotometri-cally by treating washed rat RBC
      at concentrations ranging from 30 to 300 microM of the test compounds for up to
      240 minutes. The results showed dose- and time-dependent changes in the induction
      of methemoglobin (MetHb) by aniline derivatives. The MetHb levels peaked to as
      high as 75% and remained elevated up to 240 minutes, depending on the
      electronegativity of halogenated phenylhydroxylamine aniline. This study supports
      the previous findings that there may be several aniline-derived metabolites other
      than PHA that are capable of inducing MetHb. The minimum dose required to induce
      this effect and duration of the MetHb may vary with the test agent.

PMID- 15715510
TI  - Hemolytic potential of structurally related aniline halogenated hydroxylamines.
AB  - This study was undertaken to investigate the hemolytic potential of several
      structurally related aniline halogenated phenylhydroxylamines based on their
      decreasing electro negativity. The compounds compared are phenylhydroxylamine
      (PHA) and para-fluoro-, para-bromo-, and para-iodo-phenylhydroxylamines. Red
      blood cells of male Sprague-Dawley rats were labeled with radioactive chromium-51
      and exposed to the test agent before being infused into the tail vein of
      isologous rats. The time course of blood radioactivity was monitored. The
      stability of some selected halogenated aniline analogs was also determined in
      blood. All four tested hydroxylamines produced dose-dependent reduction in the
      circulating labeled red blood cells indicating their destruction and loss. The
      most pronounced reduction was observed at doses from 175 to 250 microM. The dose
      of 100 microM appeared to be the threshold limit. The para-iodo-PHA was two times
      more toxic than para-fluoro-PHA in the destruction of red blood cells in rats.

PMID- 15715511
TI  - In memoriam: Charles H. Ross, Jr., teacher, beloved friend, inspirational leader.

PMID- 15715512
TI  - A feasibility study of magnetic resonance imaging of silicone breast implants in
      Finland.
AB  - Cosmetic breast implants have become increasingly popular throughout the world.
      However, there is insufficient knowledge about the frequency and severity of
      local complications such as rupture and capsular contracture. A pilot study of 25
      Finnish women with 50 cosmetic breast implants was organized to determine the
      feasibility of conducting a magnetic resonance imaging (MRI)-based study of
      rupture incidence. The pilot investigation included a clinical examination by a
      plastic surgeon, MRI scan, and self-administered questionnaire. The participation
      rate was 100%. Implants in our study represented a cross-section of the different
      generations of implants in Finland, with implant ages varying from 4 months to 20
      years. The average implant size was 215 mL, typical in Finnish cosmetic surgery.
      MR images were evaluated by two independent readers. The first reader diagnosed
      six implants with intracapsular rupture, while the other diagnosed all implants
      as intact. The procedures of the feasibility study proved successful, and the
      results demonstrate the importance of a rigid image evaluation protocol with
      employment of well-defined rupture criteria, as well as the benefits of several
      image readers.

PMID- 15715513
TI  - Childhood obesity: a simple equation with complex variables.
AB  - The prevalence of childhood obesity is rising rapidly, as are the associated
      medical complications, including type 2 diabetes, hypertension, and coronary
      heart disease. This has significant medical and socioeconomic implications. The
      definition of obesity in adults is based on body mass index (BMI), which has been
      correlated with morbidity and mortality. Similarly, the definition of childhood
      obesity is currently based on BMI; however, there are currently no data to relate
      morbidity and mortality to BMI values in children. The known and potential causes
      of childhood obesity are many, but they can be categorized as genetic, endocrine,
      prenatal/early life, physical activity, diet, and socioeconomic. These factors
      influence the basic equation: energy input = energy output. Imbalances in this
      equation can result in obesity. Here we present a review of recent literature and
      highlight the etiologies, certain complications, and potential prevention and
      treatment strategies of childhood obesity.

PMID- 15715514
TI  - A biomechanical study of unilateral posterior atlantoaxial transarticular screw
      fixation.
AB  - The purpose of this study was to investigate the fixation of C1-C2 instability
      with the use of a unilateral screw. Transarticular screw placement across C1-C2
      may be contra-indicated in up to 20% of specimens on at least one side because of
      anatomic variations or other pathological processes. Hence the current study
      looks into unilateral screw fixation of C1- C2 instability. Eight cervical spine
      specimens, C1 through C5, were harvested from fresh human cadavers (4 male and 4
      female) of average age 67 years (54-80). C1 and C2-C5 vertebrae were potted to
      allow motion only at the C1-C2 articulation. Cutting the transverse ligament on
      both sides of the odontoid and the tectorial membrane destabilized the specimens.
      Transarticular screw fixation of C1-C2 was performed in a manner similar to the
      technique described by Magerl. The stability was tested after fixation with one
      transarticular screw together with a posterior graft and wire. Placement of the
      screw was randomized, resulting in half the specimens receiving screws on the
      right side and the remaining half on the left side. The stiffness of the C1-C2
      articulation was tested in rotation, lateral bending, flexion, and anterior
      translation in random order. The rotational stiffness was 1.44 +/- 0.44 N-m/deg,
      while lateral bending stiffness values were 2.33 +/- 1.14 N-m/mm (right bending)
      and 2.81 +/- 1.36 N-m/mm (left bending). The stiffness value in flexion was 0.813
      +/- 0.189 N-m/mm and in translation 67.1 +/- 25.1 N/m. It was found that
      stability after unilateral transarticular screw fixation was less than that
      previously reported after bilateral transarticular screw fixation, but similar to
      that found with modified Brooks posterior wiring, which has been shown to provide
      better stability than other posterior wiring methods, and fusion rates of 96%
      have been reported. We concluded that C1-C2 unilateral posterior transarticular
      screw fixation with supplemental posterior graft and wiring would confer adequate
      stability in cases where bilateral screw placement is contraindicated.

PMID- 15715515
TI  - Effect of vascular stent alloys on expression of cellular adhesion molecules by
      endothelial cells.
AB  - OBJECTIVE: Nickel and cobalt ions activate ICAM1 expression on endothelial cells
      and keratinocytes. Furthermore, these ions are released in vitro and in vivo from
      the types of alloys used for vascular stents, but the full biological
      consequences of this release is not known. In the current study, we determined if
      release of elements from vascular stent alloys that contained nickel and cobalt
      was sufficient to activate expression of key cellular adhesion molecules (CAMs)
      by endothelial cells. Expression of these CAMs is a critical step in the long
      term inflammatory response to stent materials and possibly to in-stent
      restenonsis. METHODS: Stainless steel, NiTi, CoCrNi, and NiCr alloys were placed
      in direct contact with primary human microvascular endothelial cells for 72 hours
      after preparation at three roughnesses (120, 320, and 1200 grit). Expression of
      three CAMs--ICAM1, VCAM1, and e-selectin--was assessed using a modified ELISA
      procedure. Cytotoxicity of the alloys was assessed by measuring succinate
      dehydrogenase (SDH) activity and total protein content of the cells, and nickel
      release was measured by atomic absorption spectroscopy. RESULTS: None of the
      alloys suppressed SDH activity or total cellular protein significantly at any
      surface roughness, indicating little or no cytotoxicity. Ni release was
      measurable from all alloys, was greatest from the rougher surfaces, and was
      significantly different for the different alloy types. NiTi alloys exhibited the
      lowest nickel release. However, none of the alloys activated expression of the
      CAMs, regardless of surface roughness or nickel release level. Supplemental
      experiments using nickel ions alone confirmed that ICAM1 was inducible on the
      endothelial cells by Ni(II) concentrations above 100 microM. CONCLUSIONS: In this
      in vitro system, nickel or other elemental release from several common types of
      stent alloys was not sufficient to activate expression of CAMs on endothelial
      surfaces. Although these results indicate a low risk for direct activation of
      endothelial cells by ions released from stent alloys, other mechanisms, such as
      modulation of CAM expression by monocytes or smooth muscle cells, must be
      considered before ion-mediated influence on CAM expression can be dismissed.

PMID- 15715516
TI  - The University of Virginia Telemedicine Program: traversing barriers beyond
      geography.
AB  - Access to specialty healthcare remains inadequate for many of our rural citizens,
      a situation attributable to a host of factors ranging from geographic to economic
      barriers, worsened by the limited numbers of specialists who practice in rural
      communities. We wish to report our progress in the development of a robust 55
      site telehealth network in the Commonwealth of Virginia, designed specifically to
      enhance access to specialty care not locally available in rural regions of the
      state. We will review the process by which we developed partnerships with
      otherwise unaffiliated healthcare facilities, the equipment and
      telecommunications services used, and the statutory, regulatory, and cultural
      impediments to the fullest deployment of telehealth facilitated healthcare and
      education. Through this network, early and timely intervention has saved lives,
      avoided unnecessary transfer and travel, and initiated previously unavailable
      screening and education programs in many rural communities.

PMID- 15715517
TI  - Massive soft tissue infections: necrotizing fasciitis and purpura fulminans.
AB  - Necrotizing fasciitis and purpura fulminans are two destructive infections that
      involve both skin and soft tissue. Necrotizing fasciitis is characterized by
      widespread necrosis of subcutaneous tissue and the fascia. Historically, group A
      beta-hemolytic streptococcus has been identified as a major cause of this
      infection. However, this monomicrobial infection is usually associated with some
      underlying cause, such as diabetes mellitus. During the last two decades,
      scientists have found that the pathogenesis of necrotizing fasciitis is
      polymicrobial. The diagnosis of necrotizing fasciitis must be made as soon as
      possible by examining the skin inflammatory changes. Magnetic resonance imaging
      is strongly recommended to detect the presence of air within the tissues.
      Percutaneous aspiration of the soft tissue infection followed by prompt Gram
      staining should be conducted with the "finger-test" and rapid-frozen section
      biopsy examination. Intravenous antibiotic therapy is one of the cornerstones of
      managing this life-threatening skin infection. Surgery is the primary treatment
      for necrotizing fasciitis, with early surgical fasciotomy and debridement.
      Following debridement, skin coverage by either Integra Dermal Regeneration
      Template or AlloDerm should be undertaken. Hyperbaric oxygen therapy complemented
      by intravenous polyspecific immunoglobulin are useful adjunctive therapies.
      Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic
      infarction of the skin; it is rapidly progressive and accompanied by vascular
      collapse. There are three types of purpura fulminans: neonatal purpura fulminans,
      idiopathic or chronic purpura fulminans, and acute infectious purpura fulminans.
      Clinical presentation of purpura fulminans involves a premonitory illness
      followed by the rapid development of a septic syndrome with fever, shock, and
      disseminated intravascular coagulation. The diagnosis and treatment of these
      conditions is best accomplished in a regional burn center in which management of
      multiple organ failure can be conducted with aggressive debridement and
      fasciotomy of the necrotic skin. The newest revolutionary advancement in the
      treatment of neonatal purpura fulminans is the use of activated protein C.

PMID- 15715518
TI  - Cold injuries.
AB  - Exposure to cold can produce a variety of injuries that occur as a result of
      man's inability to adapt to cold. These injuries can be divided into localized
      injury to a body part, systemic hypothermia, or a combination of both. Body
      temperature may fall as a result of heat loss by radiation, evaporation,
      conduction, and convection. Hypothermia or systemic cold injury occurs when the
      core body temperature has decreased to 35 degrees C (95 degrees F) or less. The
      causes of hypothermia are either primary or secondary. Primary, or accidental,
      hypothermia occurs in healthy individuals inadequately clothed and exposed to
      severe cooling. In secondary hypothermia, another illness predisposes the
      individual to accidental hypothermia. Hypothermia affects multiple organs with
      symptoms of hypothermia that vary according to the severity of cold injury. The
      diagnosis of hypothermia is easy if the patient is a mountaineer who is stranded
      in cold weather. However, it may be more difficult in an elderly patient who has
      been exposed to a cold environment. In either case, the rectal temperature should
      be checked with a low-reading thermometer. The general principals of prehospital
      management are to (1) prevent further heat loss, (2) rewarm the body core
      temperature in advance of the shell, and (3) avoid precipitating ventricular
      fibrillation. There are two general techniques of rewarming--passive and active.
      The mechanisms of peripheral cold injury can be divided into phenomena that
      affect cells and extracellular fluids (direct effects) and those that disrupt the
      function of the organized tissue and the integrity of the circulation (indirect
      effects). Generally, no serious damage is seen until tissue freezing occurs. The
      mildest form of peripheral cold injury is frostnip. Chilblains represent a more
      severe form of cold injury than frostnip and occur after exposure to nonfreezing
      temperatures and damp conditions. Immersion (trench) foot, a disease of the
      sympathetic nerves and blood vessels in the feet, is observed in shipwreck
      survivors or in soldiers whose feet have been wet, but not freezing, for long
      periods. Patients with frostbite frequently present with multisystem injuries
      (e.g., systemic hypothermia, blunt trauma, substance abuse). The freezing of the
      corneas has been reported to occur in individuals who keep their eyes open in
      high wind-chill situations without protective goggles (e.g., snowmobilers, cross
      country skiers).

PMID- 15715519
TI  - Better trauma care. How Maryland does it.
AB  - In March, 1970, the Maryland State Police, in cooperation with the University of
      Maryland, started the first statewide airborne transportation system. It was
      modeled after the army's success in Korea and Vietnam, where battlefield injuries
      were flown to front-line MASH units. The world's premier statewide medical
      aviation division was made possible through a cooperative effort between the
      Maryland State Police Aviation Division and Dr. R Adams Cowley at the University
      of Maryland Hospital as a public service to the citizens of the state. The
      Maryland Institute for Emergency Medical Services Systems (MIEMSS) has five
      components: (1) aircraft, (2) state troopers, (3) system communications (SYSCOM)
      center, (4) ambulance and fire emergency rescue, and (5) Level I adult and
      pediatric trauma centers and a regional burn center. The Maryland State Police
      Aviation Division now has 12 Aerospace Dauphin AS365N helicopters that operate
      out of eight fixed points throughout the state. Each helicopter has a two-person
      crew that consists of a pilot and a paramedic. Since 1993, the overall
      coordination of emergency medical services (EMS) has been under the purview of
      MIEMSS, an independent executive-level state agency that is governed by an
      appointed board and advisory council. To ensure stable funding for Maryland's
      world renowned emergency medical services (EMS) system, including med-evac
      helicopters, ambulances, fire equipment, rescue squads, and trauma units, a
      "surcharge" of $13.50 per year is collected with the automobile registration fee
      where applicable. The SYSCOM center in Baltimore coordinates the helicopter
      transport to the scene of the accident as well as referral to the specialty care
      facility: Adult Level I Trauma Center, Pediatric Level I Trauma Center, and
      Regional Burn Center. An on-the-scene evaluation of this exemplary emergency
      medical system in Maryland provides further convincing evidence of the
      performance of the Maryland State Police Aviation Division as they transported an
      injured child to the Johns Hopkins Pediatric Level I Trauma Center. It is our
      belief that the model emergency medical system in Maryland, if replicated
      throughout our nation, would save the lives of the critically injured.

PMID- 15715520
TI  - Vaccine information statements. Revolutionary but neglected educational advances
      in healthcare in the United States.
AB  - The purpose of this report is to provide further information about vaccine
      information statements (VISs) that are revolutionary but neglected educational
      advances in the United States. Because the use of VISs is mandated by the Federal
      Government in every individual being immunized, it is the goal of this report to
      further awaken health professionals and society to the mandatory use of these
      superb educational statements. With the passage of the National Childhood Vaccine
      Injury Act of 1986, the Federal Government required that VISs would be given to
      all vaccine recipients. As of September 2001, the VISs that must be used are
      diphtheria, tetanus, pertussis, (DTaP); diphtheria, tetanus (Td); measles, mumps,
      rubella (MMR); polio (IPV); hepatitis B; Haemophilus influenzae type b (Hib);
      varicella; and pneumococcal conjugate. Copies of the VISs are available at
      www.cdc.gov/nip/publications/VIS. The National Childhood Vaccine Injury Act of
      1986 mandated that all health care providers report certain adverse events that
      occur following vaccination. As a result, the Vaccine Adverse Events Reporting
      System (VAERS) was established by the FDA and the Centers for Disease Control and
      Prevention (CDC) in 1990. In order to reduce the liability of manufacturers and
      healthcare providers, the National Childhood Vaccine Injury Act of 1986
      established the National Vaccine Injury Compensation Program (NVICP). This
      program is intended to compensate those individuals who have been injured by
      vaccines on a no-fault basis. While the use of VISs has been mandated since 1996,
      a national survey of private practice office settings has revealed that many
      immunized patients do not receive the VISs. When these forms were used,
      physicians rarely initiated discussions regarding contraindications to
      immunizations or the National Vaccine Injury Compensation Program. Fortunately,
      the state boards of medical examiners, like the one in Oregon, are taking a
      strong stand for the use of VISs, with the warning that failure to use a VIS may
      result in disciplinary action. Our nation and practicing physicians must be
      awakened to the importance of the use of VISs to ensure that every vaccinated
      individual receives this statement at the time of vaccination.

PMID- 15715521
TI  - Cross down-regulation of leptin and insulin receptor expression and signalling in
      a human neuronal cell line.
AB  - Leptin and insulin are major signals to the hypothalamus to regulate energy
      homoeostasis and body adiposity. IR (insulin receptors) and leptin receptors
      (long isoform, ObRb) share a number of signalling cascades, such as JAK2/STAT-3
      (Janus kinase 2/signal transduction and activator of transcription 3) and PI3K
      (phosphoinositide 3-kinase); the cross-talk between IR and ObRb have been
      described previously in non-neuronal cells. Differentiated human neuroblastoma
      (SH-SY5Y) cells express endogenous ObR and IR, and respond to leptin and insulin
      with stimulation of STAT-3 and MAPK (mitogen-activated protein kinase)
      phosphorylation, and PI3K activity. Insulin or leptin pre-treatment of SH-SY5Y
      cells increased basal STAT-3 phosphorylation, but abolished the acute effect of
      these hormones, and, interestingly, leptin pre-treatment abolished insulin effect
      and vice versa. Similar results were obtained for MAPK phosphorylation, but
      leptin or insulin pre-treatment did not completely abolish the acute effect of
      insulin or leptin. We have also showed that insulin and leptin are able to
      activate PI3K through IRS-1 (insulin receptor substrate 1) and IRS-2
      respectively. Furthermore, leptin or insulin pre-treatment increased basal PI3K
      activity and IRS-1 or IRS-2 association with p85 and abolished acute insulin or
      leptin effect, in addition to the down-regulation of IRS-1 and IRS-2. Finally,
      insulin pre-treatment reduced leptin binding by approx. 60%, and leptin pre
      treatment reduced the expression of insulin receptor by 40% in SH-SY5Y cells,
      which most likely accounts for the cross down-regulation of leptin and insulin
      receptors. These results provide evidence to suggest cross down-regulation of
      leptin and insulin receptors at both receptor and downstream signalling levels.
      This finding may contribute to the understanding of the complex relationship
      between leptin resistance and insulin resistance at the neuronal level.

PMID- 15715522
TI  - Characterization of the inactivation of rat fatty acid synthase by C75:
      inhibition of partial reactions and protection by substrates.
AB  - C75, a synthetic inhibitor of FAS (fatty acid synthase), has both anti-tumour and
      anti-obesity properties. In this study we provide a detailed kinetic
      characterization of the mechanism of in vitro inhibition of rat liver FAS. At
      room temperature, C75 is a competitive irreversible inhibitor of the overall
      reaction with regard to all three substrates, i.e. acetyl-CoA, malonyl-CoA and
      NADPH, exhibiting pseudo-first-order kinetics of the complexing type, i.e. a weak
      non-covalent enzyme-inhibitor complex is formed before irreversible enzyme
      modification. C75 is a relatively inefficient inactivator of FAS, with a maximal
      rate of inactivation of 1 min(-1) and an extrapolated K(I) (dissociation constant
      for the initial complex) of approx. 16 mM. The apparent second-order rate
      constants calculated from these values are 0.06 mM(-1).min(-1) at room
      temperature and 0.21 mM(-1).min(-1) at 37 degrees C. We also provide experimental
      evidence that C75 inactivates the beta-ketoacyl synthase (3-oxoacyl synthase)
      partial activity of FAS. Unexpectedly, C75 also inactivates the enoyl reductase
      and thioesterase partial activities of FAS with about the same rates as for
      inactivation of the beta-ketoacyl synthase. In contrast with the overall
      reaction, the beta-ketoacyl synthase activity and the enoyl reductase activity,
      substrates do not protect the thioesterase activity of rat liver FAS from
      inactivation by C75. These results differentiate inactivation by C75 from that by
      cerulenin, which only inactivates the beta-ketoacyl synthase activity of FAS, by
      forming an adduct with an active-site cysteine. Interference by dithiothreitol
      and protection by the substrates, acetyl-CoA, malonyl-CoA and NADPH, further
      distinguish the mechanism of C75-mediated inactivation from that of cerulenin.
      The most likely explanation for the multiple effects observed with C75 on rat
      liver FAS and its partial reactions is that there are multiple sites of
      interaction between C75 and FAS.

PMID- 15715524
TI  - Wnt, stem cells and cancer in the intestine.
AB  - The intestinal epithelium is a self-renewing tissue which represents a unique
      model for studying interconnected cellular processes such as proliferation,
      differentiation, cell migration and carcinogenesis. Although the stem cells of
      the intestine have not yet been physically characterized or isolated, data over
      the past decade have strongly implicated the Wnt/beta-catenin signalling pathway
      in their maintenance and progression to cancer. This review will (i) describe the
      distinctive features of the intestinal epithelium in relation to stem-cell
      function, (ii) illustrate the major genetic alterations that can lead to cancer,
      and (iii) show how Wnt/beta-catenin signalling controls homoeostasis in this
      tissue.

PMID- 15715525
TI  - What does it take to make a heart?
AB  - Ever increasing advances are being made in our quest to understand what it takes
      to direct pluripotent precursor cells to adopt a specific developmental fate.
      Eventually, the obvious goal is that targeted manipulation of these precursor
      cells will result in an efficient and reliable production of tissue-specific
      cells, which can be safely employed for therapeutic purposes. We have gained an
      incredible insight as to which molecular pathways are involved in governing
      neural, skeletal and cardiac muscle fate decisions. However, we still face the
      challenge of how to direct, for example, a cardiac fate in stem cells in the
      amounts needed to be employed for regenerative means. Equally importantly, we
      need to resolve critical questions such as: can the in vitro generated
      cardiomyocytes actually functionally replace damaged heart tissue? Here I will
      provide an overview of the molecules and signalling pathways that have first been
      demonstrated in embryological studies to function in cardiogenesis, and summarize
      how this knowledge is being applied to differentiate mouse and human embryonic
      stem cells into cardiomyocytes.

PMID- 15715523
TI  - Epidermal stem cells: the cradle of epidermal determination, differentiation and
      wound healing.
AB  - The field of epidermal stem cells has dramatically advanced in the last decade,
      leading to a better understanding of the molecular factors, signalling pathways
      and cellular events that identify and characterize stem cells, thus revealing
      their immense potential for therapeutic use. Furthermore, multipotent epidermal
      stem cells present the major advantage of easy accessibility with the discovery
      of their specific location within the bulge of the hair follicle. This review
      focuses on the most recent findings on epidermal stem cells, and their potential
      role in initial epidermal commitment, differentiation and wound healing processes
      in the skin.

PMID- 15715526
TI  - Application of RNA interference to study stem cell function: current status and
      future perspectives.
AB  - RNA interference is a mechanism displayed by most eukaryotic cells to rid
      themselves of foreign double-stranded RNA molecules. In the six years since the
      initial report, RNA interference has now been demonstrated to function in
      mammalian cells to alter gene expression, and has been used as a means for
      genetic discovery as well as a possible strategy for genetic correction. An
      equally popular topic over the past six years has been the proposal to utilize
      embryonic stem cells or adult stem cells as cell-based therapies for human
      diseases. The aim of this review is to provide a general overview of how RNA
      interference suppresses gene expression and to examine some published RNA
      interference approaches that have resulted in changes in stem cell function and
      suggest the possible clinical relevance of this work.

PMID- 15715527
TI  - Role of progestins in contraception.
AB  - Progestins have been used for contraception for more than 30 years. The main goal
      was to develop a contraceptive method devoid of the metabolic or clinical side
      effects associated with the use of estrogens. The development of new
      contraceptive methods and formulations is time-consuming and requires devotion,
      belief, and also strong economical basis. As a result of this endeavor new
      methods have been developed: oral progestins, implants, injectables, intrauterine
      hormonal systems, and vaginal rings. Progestin-only contraceptives may be
      preferable in some situations, which have absolute or relative contraindications
      to estrogen, side-effects to estrogen containing hormonal contraception,
      lactation, and comfort and feasibility of formulations for long-term use. At
      present, emergency contraception is also performed with progestin.

PMID- 15715528
TI  - Normal labor associated with changes in uterine heparan sulfate proteoglycan
      expression and localization.
AB  - HYPOTHESIS: Proteoglycans are well-known modulators of intercellular
      communication and signaling. Remodeling of the proteoglycans in the human uterus
      occurs throughout pregnancy, and during labor. We therefore hypothesize that
      heparan sulfate proteoglycans (HSPGs) play an important role in establishing
      normal labor. In this study HSPGs were characterized and localized in human
      uterine tissue. METHODS: Uterine biopsies were obtained from four nonpregnant
      women, four women during elective cesarean section and four during emergency
      cesarean section. The biopsies were extracted using 4 m guanidinium hydrochloride
      (GuHCL). HSPGs were then purified by repeated ion-exchange chromatography on
      dehydroepiandrosterone (DEAE)-cellulose after digestion with chondroitinase ABC
      and finally precipitated with Alcian blue. HSPGs were identified by agarose gel
      electrophoresis and Western blotting. Controlled degradation of the heparan
      sulfate (HS) side-chains was performed using heparitinase or deglycosylation with
      trifluoromethanesulfonic acid (TFMS). The resulting core proteins were separated
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      visualized by Coomassie staining. HSPGs were localized in uterine tissue by
      immunohistochemistry. RESULTS: SDS-PAGE after deglycosylation indicated the
      presence of multiple distinct core proteins tentatively identified as syndecans 1
      4 and glypican 1. Western blots confirmed the presence of these proteoglycans and
      also perlecan. Immunohistochemistry revealed that the HSPGs were localized mainly
      in the smooth muscle with few in the extracellular matrix (ECM). Syndecan 3, the
      dominant proteoglycan, showed the most pronounced changes during pregnancy and
      labor. CONCLUSION: For the first time several heparan sulfate proteoglycans have
      been identified and localized in the human uterus and shown to vary in expression
      during pregnancy and labor. Syndecan 3 had the most outstanding features in this
      respect.

PMID- 15715529
TI  - Effect of vaginal distension on anorectal function: identification of the vagino
      anorectal reflex.
AB  - BACKGROUND: Sexual stimulation produces not only reflex changes in the female
      external and internal reproductive organs but also extragenital reactions. A
      mention of the response of the anal sphincters and the rectum to penile thrusting
      could not be traced in the literature. We investigated the hypothesis that the
      anal sphincters and the rectum respond to penile thrusting in a way that prevents
      gas and fecal leakage during sexual intercourse. METHODS: The response of the
      external anal sphincter (EAS) and the internal anal sphincter (IAS) and the
      rectum to vaginal balloon (condom) distension was recorded in 23 healthy women
      (age: 33.7 +/- 7.3 years). The vaginal condom was inflated with air in increments
      of 50-300 ml, and the electromyographic (EMG) activity of the EAS and the IAS, as
      well as rectal pressure, was recorded. The test was repeated after separate
      anesthetization of the vagina, the rectum, the EAS and the IAS and after the use
      of normal saline instead of lidocaine. RESULTS: Vaginal distension reduced the
      rectal pressure in the ratio of expansion of the vaginal volume up to a certain
      volume, beyond which the rectal pressure ceased to decline when more distending
      volume was added. Similarly, the internal sphincter EMG activity increased
      progressively on incremental vaginal distension increase until the 150-ml
      distension was reached after which more vaginal distension caused no further
      increase of the EMG activity; external sphincter EMG activity showed no response.
      Vaginal distension, while the vagina, the rectum, the EAS, and the IAS had been
      separately anesthetized, produced no significant change, but saline did.
      CONCLUSIONS: Vaginal balloon distension appears to effect rectal wall relaxation
      and increase of the internal sphincter tone. This seems to provide a mechanism to
      avoid rectal contents leakage during coitus. Rectal and internal sphincter
      response to vaginal distension is suggested to be mediated through a reflex we
      term 'vagino-anorectal reflex', which seems to be evoked by vaginal distension
      during penile thrusting. The reflex may prove of diagnostic significance in
      sexual disorders; further studies are needed in order to investigate this point.

PMID- 15715530
TI  - Normative values of Doppler velocimetry of five major fetal arteries as
      determined by color power angiography.
AB  - OBJECTIVE: To produce normograms of Doppler indices of major fetal arteries and
      their ratios relative to the ascending aorta in a cohort of appropriately grown
      for gestational age fetuses. METHODS: Prospective longitudinal study of 70 women
      with appropriately grown for gestational age fetuses between 24 and 38 weeks'
      gestation attending the Fetal Growth Clinic of a large UK teaching hospital.
      Doppler velocimetry of the middle cerebral (MCA), umbilical (UmA) and renal
      arteries (RA) and the ascending (AAO) and descending (DAO) aortas were studied
      using color power angiography. Ratios of the Doppler indices [pulsatility index
      (PI), resistance index (RI), systolic/diastolic (S/D) ratio] were then calculated
      using the ascending aorta as the reference numerator for the other four vessels
      to produce normograms. Regression analysis was performed to determined the
      significance, if any, of the changes in these ratios with gestation. RESULTS: The
      normograms of the various Doppler indices were similar for the middle cerebral
      artery, ascending and descending aortas. There was an initial rise to a peak
      between 30 and 32 weeks and then a gradual return to values at 38 weeks similar
      to those at 24 weeks' gestation. In the renal artery, the indices showed very
      little variation with gestation. However, there was a gradual fall in the indices
      with gestation in the umbilical artery. The ratios of the various indices
      relative to that of the ascending aorta demonstrated an increase with gestation.
      The changes with gestation were statistically significant for the ratios of the
      indices from the ascending aorta to those of the middle cerebral, renal and
      umbilical arteries but not for those of the descending aorta. CONCLUSIONS: The
      vascular resistance in the five fetal arteries decreased towards the end of
      pregnancy and the ratios of their indices relative to those of the ascending
      aorta decreased from 24 to 38 weeks' gestation. Early subtle changes in
      circulation in compromised fetuses may be identified early from deviations in
      these normograms.

PMID- 15715531
TI  - Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose-
      response study of 20-80 mg ferrous iron daily in pregnant women.
AB  - OBJECTIVE: To determine the lowest dose of iron preventative of iron deficiency
      and iron deficiency anemia in pregnancy. METHODS: A randomized, double-blind
      intention-to-treat study comprising 427 healthy pregnant women allocated into
      four groups taking ferrous iron (as fumarate) in doses of 20 mg (n = 105), 40 mg
      (n = 108), 60 mg (n = 106), and 80 mg (n = 108) from 18 weeks of gestation. Iron
      status markers [hemoglobin (Hb), serum ferritin, and serum soluble transferrin
      receptor (sTfR)] were measured at 18 weeks (inclusion), 32 weeks, and 39 weeks of
      gestation and 8 weeks postpartum. Side effects of iron supplements were recorded.
      Iron deficiency was defined as serum ferritin <13 microg/l and iron deficiency
      anemia as serum ferritin <13 microg/l and Hb <5th percentile in iron replete
      pregnant women. RESULTS: There were no significant differences between variables
      in the four groups at inclusion. At 32 and 39 weeks of gestation, group 20 mg had
      significantly lower median serum ferritin (13 and 16 microg/l) than group 40 mg
      (17 and 21 microg/l), group 60 mg (18 and 23 microg/l), and group 80 mg (21 and
      24 microg/l) (p < 0.0001). At 32 and 39 weeks of gestation, group 20 mg had a
      significantly higher prevalence of iron deficiency (50 and 29%) than group 40 mg
      (26 and 11%), group 60 mg (17 and 10%), and group 80 mg (13 and 9%) (p < 0.001).
      The prevalence of iron deficiency anemia at 39 weeks of gestation was
      significantly higher in group 20 mg (10%) than in group 40 mg (4.5%), group 60 mg
      (0%), and group 80 mg (1.5%) (p = 0.02). At 32 weeks of gestation, mean Hb in
      group 20 mg was lower than in group 80 mg (p = 0.06). There were no significant
      differences in iron status (ferritin, sTfR, and Hb) between group 40, 60, and 80
      mg. Postpartum, group 20 mg had significantly lower median serum ferritin than
      group 40, 60, and 80 mg (p < 0.01). The prevalence of postpartum iron deficiency
      anemia was low and similar in the four groups. The frequency of gastrointestinal
      symptoms was not significantly different in the four iron supplement groups and
      thus not related to the iron dose. CONCLUSION: In Danish women, a supplement of
      40 mg ferrous iron/day from 18 weeks of gestation appears adequate to prevent
      iron deficiency in 90% of the women and iron deficiency anemia in at least 95% of
      the women during pregnancy and postpartum.

PMID- 15715533
TI  - Autologous blood transfusion in patients with placenta previa.
AB  - BACKGROUND: Several studies have shown that autologous blood storage during
      pregnancy is relatively safe for mother and fetus. However, the need for
      reappraisal of autologous blood transfusion in obstetric patients has been
      proposed. METHODS: We retrospectively reviewed the cases of placenta previa and
      low-lying placenta among pregnancies at our hospital during an 18-year period,
      1985-2002. The utility of autologous blood transfusion program, which started in
      1994 for those with placental positional disorders, was evaluated. RESULTS: Of
      the pregnancies reviewed, there were 158 cases (1.9%) of placenta previa or low
      lying placenta. The number of patients transfused with homologous blood decreased
      from 27.6% (21/76) in the period before implementation of the autologous blood
      transfusion program to 8.5% (7/82) after its implementation in 1994. In the
      latter time period, 39.0% (32/82) of patients with placenta previa and low-lying
      placenta were phlebotomized and had blood stored. Of those, 71.9% (23/32) were
      reinfused where one patient (3.1%) needed homologous blood as well. The volume of
      collected blood per phlebotomy was 367 +/- 65 ml, the total volume of collected
      blood per patient was 803 +/- 350 ml, and the total of estimated blood loss per
      patient was 1326 +/- 873 ml. The volume of reinfused blood per patient was 578 +/
      326 ml. CONCLUSIONS: The program of autologous blood collection and transfusion
      in patients with placenta previa resulted in a decrease in homologous blood
      transfusion. In our program, we recommend starting blood collection and storage
      at 32 weeks' gestation and phlebotomize 400 ml per week to reach a volume of
      stored blood of 1200-1500 ml.

PMID- 15715532
TI  - Number of antenatal visits and women's opinion.
AB  - BACKGROUND: The national recommendation in Sweden regarding number of antenatal
      care visits was reduced in 1996. The aim of this study was to explore the factors
      associated with number of visits made and with women's own opinions about these
      visits. Another aim was to study associations between the number of visits and
      satisfaction with antenatal care overall. METHODS: All Swedish-speaking women who
      came for their first visit to the midwife in 593 participating clinics during 3
      weeks evenly spread over 1 year in 1999-2000 were invited to participate in the
      study. Information was collected by postal questionnaires after the booking visit
      and 2 months after childbirth. Cases of preterm delivery and intrauterine death
      were excluded. RESULTS: After excluding miscarriages, non-Swedish-speaking women,
      and women booked at non-participating clinics, about 69% of all women booked in
      antenatal care were recruited. Of these, 2421 (83%) completed the two
      questionnaires. About 25% followed the standard visiting schedule for a normal
      pregnancy, 57% made more visits, and 17% fewer visits. The number of visits made
      was associated with parity, medical diagnosis, depressive symptoms, level of
      education, and women's preferences in early pregnancy. Women's own opinion that
      they made too few visits was associated with a preference for more visits in
      early pregnancy and actually receiving fewer visits than the standard schedule.
      The view that they made too many visits was associated with a previous negative
      birth experience, a wish for fewer visits, having a medical diagnosis, many
      children, and major worries. The vast majority of women (87.6%) were satisfied
      with antenatal care overall but less with emotional (76.9%) than with medical
      (82.3%) aspects. No association was found between number of visits made and
      satisfaction, but women's own opinion that they had too few visits was associated
      with dissatisfaction with medical as well as emotional aspects of care and the
      opinion that they made too many visits with the emotional aspects of care.
      CONCLUSION: Two-thirds of the women did not follow the standard visiting
      schedule, the majority of women made more visits. The number of antenatal visits
      seemed to be fairly well adapted to women's individual needs and, to some extent,
      to their own wishes. Very few women were dissatisfied with the number of visits
      made as well as the antenatal care overall.

PMID- 15715534
TI  - Postpartum hemorrhage: a prospective, comparative study in Angola using a new
      disposable device for oxytocin administration.
AB  - BACKGROUND: Postpartum hemorrhage (PPH) is the single most common cause of
      maternal death in the world, and oxytocin is known to be effective for its
      prevention and treatment. The use of syringes can be problematic in areas
      affected by HIV. The aim of this study was to introduce Uniject (a new disposable
      device for administration of 10 IU oxytocin) as part of active management of the
      third stage of labor (AMTL) and try to reduce PPH. METHODS: A prospective,
      comparative study was performed between March 1998 and May 2000 in Luanda. Seven
      hundred and eighty-two parturient women with physiological management were
      compared to 814 with AMTL. Postpartum lost blood was collected using a plastic
      sheet during labor and a bucket placed under a cholera bed for 2 h postpartum.
      Student's t-test and chi(2) test were used. RESULT: PPH was reduced from 40.4 to
      8.2% and severe PPH (> or =1000 ml) from 7.5 to 1% in the AMTL group (P < 0.001).
      CONCLUSIONS: Uniject was well tolerated and offers an alternative for oxytocin
      administration. AMTL should be implemented also in resource-poor settings as a
      routine management to reduce PPH.

PMID- 15715535
TI  - The effect of placental removal method and site of uterine repair on postcesarean
      endometritis and operative blood loss.
AB  - BACKGROUND: Our purpose was to determine whether blood loss during cesarean
      section and postoperative endometritis rate were associated with the method of
      placental removal and site of uterine repair. METHODS: This prospective
      randomized study involved 840 women who underwent cesarean section. The patients
      were grouped into four: (1) manual placental delivery + exteriorized uterine
      repair; (2) spontaneous placental delivery + exteriorized uterine repair; (3)
      manual placental delivery + in situ uterine repair; (4) spontaneous placental
      delivery + in situ uterine repair. Patients were excluded if they had received
      intrapartum antibiotics, had chorioamnionitis, required an emergency cesarean
      hysterectomy, had rupture of membranes for more than 12 hr, had bleeding
      diathesis, and had abnormal placentation or prior postpartum hemorrhage. The main
      outcome measures were postoperative hemoglobin and hematocrit values, and
      postcesarean endometritis. RESULTS: There were no statistically significant
      differences in mean maternal age, parity, gestational age, presence and duration
      of membrane rupture and number of vaginal examinations between the four groups.
      The decrease in postoperative hemoglobin (P < 0.05) and hematocrit (P < 0.001)
      was significantly greater in the manual removal groups (groups 1 and 3) than in
      the spontaneous expulsion groups (groups 2 and 4) at 48 hr postoperatively. The
      incidence of postoperative endometritis was significantly higher in manual
      removal groups (15.2%) (groups 1 and 3) than in spontaneous groups (5.7%) (groups
      2 and 4) (P < 0.05). CONCLUSIONS: Manual removal of the placenta at cesarean
      delivery results in more operative blood loss and a higher incidence of
      postcesarean endometritis.

PMID- 15715536
TI  - Attitudes and practices of private medical providers towards family planning and
      abortion services in Nigeria.
AB  - CONTEXT: The study was designed to investigate the attitudes and practices of
      private medical practitioners towards abortion, postabortion care and
      postabortion family planning in Nigeria. METHODS: Three hundred and twenty-three
      private practitioners who were proprietors of private clinics in three states of
      the country were interviewed with a structured questionnaire that elicited
      information on their knowledge and experiences of abortion and postabortion care
      in the cities. RESULTS: Twenty-four percent of the doctors reported that they
      routinely terminate unwanted pregnancies when requested to do so by women, while
      82% reported that they frequently treat women who experience complications of
      unsafe abortion. Over 45% reported that they use manual vacuum aspiration (MVA)
      for the management of abortion in the first trimester, while 25% use dilatation
      and curettage (D and C). Nearly 28% reported the use of MVA followed by D and C
      in the first trimester. Fifty-seven percent reported their lack of expertise in
      managing second-trimester abortions, while those admitting that they manage
      second-trimester abortions reported nonstandard methods and procedures. In
      addition, there was evidence of inadequate counseling of women, lack of
      institutional protocols and poor use of postabortion family planning by the
      doctors. CONCLUSIONS: These results suggest the need for a program of retraining
      of private practitioners on the principles and practices of safe abortion,
      postabortion care and family planning in Nigeria and the integration of these
      topics into medical training curricula in the country.

PMID- 15715537
TI  - Inhibin A and B as markers of menopause: a five-year prospective longitudinal
      study of hormonal changes during the menopausal transition.
AB  - OBJECTIVES: A more direct and precise hormonal marker of the menopause has been
      required for some time. The aim of this study was to identify the most accurate
      marker of the menopause, based on analyses of inhibin A and B, FSH, LH and
      estradiol (E(2)), among 59 healthy women without hormonal treatment during the
      perimenopause and early postmenopause. METHODS: Fifty-nine women, aged 46-56
      years (mean age 51.2 years), were examined annually for 5 years during the
      menopausal transition and had venous blood drawn simultaneously for later
      analyses of the above-mentioned hormones. RESULTS: Inhibin A showed a steady
      decline from at least 4 years before the final menstrual period (FMP) until 1
      year before menopause, whereas inhibin B had a shorter lasting decline from year
      3 to year 2 before menopause, concomitant with a rise in FSH and LH. CONCLUSION:
      The present study confirmed previous observations that inhibin A had a continuous
      decline starting before the decline of inhibin B, suggesting that an increasing
      part of the cycle was anovulatory. The fall in inhibin B and the increase in FSH
      constitute markers of ovarian aging. One year prior to menopause neither inhibin
      A nor inhibin B could be detected. The disappearance of these peptide hormones is
      an important predictor of the approaching menopause.

PMID- 15715538
TI  - Surgery for pelvic organ prolapse in women of 80 years of age and older.
AB  - BACKGROUND: To investigate the long-term results of women over 80 years of age
      following surgery for pelvic organ prolapse. Design. Retrospective, descriptive
      study. METHODS: We reviewed all records of women of 80 years and older operated
      for pelvic organ prolapse; all patients alive were contacted through a postal
      questionnaire. RESULTS: A total of 2058 operations for pelvic organ prolapse were
      performed in the study period. One hundred and twenty-eight patients were 80
      years and older with the mean age of 83 years (range 80-92 years). In three
      cases, serious complications occurred, and one of them died shortly after the
      operation. Follow-up was done with a postal questionnaire. Eighty-eight percent
      of patients who were alive at the time of data analysis returned the
      questionnaire. The mean duration of follow-up was 28 months (range 1-80 months).
      There were no patients who reported a relapse of prolapse. Urinary incontinence,
      urge, stress, or mixed incontinence, was present in almost half of the cases. The
      time to full recovery after the operation was experienced to be less than 3
      months for 48%. General satisfaction with the procedure was high with 88% being
      (very) satisfied. CONCLUSION: The operative correction of a pelvic organ prolapse
      in a group of women 80 years and older is a successful operation, with an
      acceptable morbidity and a high satisfaction of the patients.

PMID- 15715539
TI  - Reduction in hospitalized women with pelvic inflammatory disease in Oslo over the
      past decade.
AB  - BACKGROUND: A tuboovarian abscess (TOA) is a common complication of pelvic
      inflammatory disease (PID), occurring world-wide in 15-30% of women with PID. The
      aim of the study was to identify changes during the last 10 years in the number
      of women hospitalized with PID in Oslo, as well as a change regarding the
      frequencies of the subdiagnoses salpingitis and tuboovarian abscess. METHODS: We
      performed a review of computerized diagnosis lists and manual check of the
      medical records of women hospitalized with PID in Oslo. The years 1990-92 and
      2000-02 were included, resulting in information from two time periods 10 years
      apart. Cases were registered as salpingitis, oophoritis or tuboovarian abscess.
      Medical and demographic variables from the medical records of women diagnosed
      during 4 out of the 6 years were described in detail. RESULTS: We identified 523
      women with the diagnosis of PID hospitalized during 1990-92 and 2000-02. There
      was a 35% reduction in hospitalized cases of salpingitis over the period of 10
      years, but the number of cases of tuboovarian abscesses among women admitted for
      PID remained unchanged from 1990-92 to 2000-02. We found low frequencies of
      Chlamydia trachomatis and Neisseria gonorrhoea infections, although documented
      bacteriological sampling was insufficient. CONCLUSIONS: Fewer patients were
      hospitalized in Oslo for PID during the time period of 2000-02 compared with 10
      years earlier, but a higher percentage of patients had developed TOA compared
      with the first time period (43% compared with 26%, p = 0.013), indicating a
      changing clinical panorama of PID.

PMID- 15715540
TI  - Peritoneal fluid and serum concentration of interleukin-16 in women with
      endometriosis.

PMID- 15715541
TI  - Acute mesenteric ischemia: an unknown cause of immediate postcesarean mortality.

PMID- 15715542
TI  - Successful pregnancy occurring with interferon-alpha therapy in chronic myeloid
      leukemia.

PMID- 15715543
TI  - Fetal hepatic hemangioma diagnosed prenatally with ultrasonography.

PMID- 15715544
TI  - Post-embolization syndrome and complete expulsion of a leiomyoma after uterine
      artery embolization.

PMID- 15715545
TI  - Elevated plasma homocysteine levels in gestational diabetes mellitus.

PMID- 15715549
TI  - A Nordic Academy of Ophthalmology.

PMID- 15715550
TI  - Endophthalmitis following cataract surgery in Sweden: national prospective survey
      1999-2001.
AB  - PURPOSE: To investigate the epidemiology of postoperative endophthalmitis (POE)
      following cataract surgery in Sweden during a 3-year period, using the framework
      of the Swedish National Cataract Register. METHODS: Clinically presumed cases of
      POE were reported in a prospective survey involving all Swedish ophthalmic
      surgical units except one. Data on results of the intraocular culture and visual
      outcome after infection, as well as patient age and gender and various elements
      of the surgical procedure, were collected. RESULTS: The nationwide incidence of
      POE was 0.0595%, representing 112 cases in 188 151 cataract operations. Gram
      positive bacteria were the predominant aetiology, with an 84.6% share of culture
      positive cases. A significantly decreased risk for POE was found for patients who
      had received prophylactic intracameral antibiotics (mainly cefuroxime) in
      comparison with those who had been treated with topical antibiotics only.
      CONCLUSIONS: The prevalence of POE after cataract surgery in Sweden is at the
      lower end of the spectrum of incidence currently reported in the developed world.
      The administration of intracameral antibiotics may have contributed to these
      results.

PMID- 15715551
TI  - Three-year follow-up of posterior capsule opacification with two different
      silicone intraocular lenses.
AB  - PURPOSE: To compare posterior capsule opacification (PCO) after cataract surgery
      with implantation of two silicone intraocular lenses (IOLs) with different
      designs. METHODS: We carried out a prospective, clinical study of 116 patients
      randomized to standardized phacoemulsification with implantation of CeeOn Edge (n
      = 57) or SI40NB (n = 59) IOLs. The follow-up period was 3 years. To evaluate PCO
      morphologically, digital images were obtained and analysed using evaluation of
      posterior capsule opacification computer software (epco). The neodymium:YAG
      (Nd:YAG) capsulotomy rate was recorded. RESULTS: At 2 and 3 years, the eyes with
      SI40NB IOLs had significantly more PCO than those with the CeeOn Edge IOLs (p =
      0.00014 and p = 0.002). Nine Nd:YAG capsulotomies were performed in the SI40NB
      group and none in the CeeOn Edge group. This difference was statistically
      significant (p = 0.003). In some patients a regression of PCO was noticed and
      confirmed using epco. Statistically less PCO was noted when the capsulorhexis rim
      was placed so that it covered all 360 degrees of the optic of the IOL.
      CONCLUSIONS: A clinically and statistically significant difference in PCO
      development between CeeOn Edge and SI40NB IOLs at 2 and 3 years postoperatively
      was found. These findings support earlier studies indicating that a sharp edge of
      the optic is a more important factor in IOL design than IOL material in the
      prevention of PCO.

PMID- 15715552
TI  - Glare disability and spherical aberration with five foldable intraocular lenses:
      a prospective randomized study.
AB  - PURPOSE: To compare differences in subjective glare and spherical aberration
      between five foldable intraocular lenses (IOLs) made of different materials and
      to different designs. METHODS: This prospective study comprised 175 cataract
      patients who underwent phacoemulsification and were randomized to receive one of
      five types of foldable IOL (AcrySof MA30BA, Alcon; Sensar AR40, AMO; AcrySof
      SA30AL, Alcon; Sensar AR40e, AMO, and Tecnis Z9000, Pharmacia & Upjohn). All
      patients received a questionnaire investigating the incidence of subjective
      photic phenomena. Two months postoperatively, we collected data regarding
      subjective glare and evaluated pupil size, visual acuity and wavefront aberration
      of the cornea and eye. RESULTS: With regard to difficulty in performing ordinary
      activities under different light conditions and light and dark adaptation, the
      difference between the groups was not significant (p > 0.05, chi-squared test).
      With respect to difficulty in driving at night, the MA30BA group had a
      significant higher incidence of photic phenomena than the SA30AL, AR40e and Z9000
      groups (p < 0.05, chi-squared test). Wavefront measurements revealed a
      significant difference between the Z9000, AR40e and SA30AL groups, which showed
      the lowest values, and the MA30BA group, which showed the highest value (p <
      0.05, anova with Tamhane posthoc test). CONCLUSIONS: New generation IOLs such as
      the Pharmacia Z9000, AMO AR40e and AcrySof SA30AL have a lower incidence of glare
      and spherical aberrations; however, their impact on future IOL design should be
      conditioned by further data, especially regarding posterior capsule
      opacification.

PMID- 15715553
TI  - Trinitrotoluene (TNT)-induced cataract in Danish arms factory workers.
AB  - PURPOSE: To compare the prevalence of cataract in workers exposed to
      trinitrotoluene (TNT) to the prevalence in a group of unexposed workers, matched
      on age and sex, using Tiukina's description and grading of TNT-induced cataract.
      METHODS: A total of 23 TNT-exposed and 44 unexposed workers underwent an eye
      examination performed by an ophthalmologist who did not know the exposure status
      of the subjects. All lens opacities matching Tiukina's description were
      classified as TNT cataract and graded on Tiukina's scale of stages 1-4. RESULTS:
      Four cases of TNT-induced cataract were identified among the 23 TNT-exposed
      workers and none in the unexposed group (p < 0.01). CONCLUSION: Exposure to TNT
      may cause a unique type of cataract, which a general ophthalmologist, using
      Tiukina's description and grading scale, will be able to distinguish from other
      cataracts.

PMID- 15715554
TI  - Proteomic analysis of aqueous humour from patients with acute corneal rejection.
AB  - PURPOSE: To compare the basic proteomic composition of aqueous humour (AH) from
      patients with corneal rejection (patients) with AH from patients with cataract
      (controls). METHODS: Aqueous humour was analysed for total protein concentration
      using Bradford's method and for protein composition using two-dimensional (2D)
      gel electrophoresis. Image analysis was used to detect protein spots in 2D gels
      that were increased by more than factor 2 in patients as compared with controls.
      Increased spots were identified by immunoblotting and mass spectrometry. RESULTS:
      Aqueous humour from patients contained significantly higher total protein
      concentration than did AH from controls. A total of 31 spots were significantly
      increased in 2D gels from patients. The spots were derived from albumin, alpha1
      antitrypsin, apolipoprotein J, cytokeratin type II, serin proteinase inhibitor
      and transthyretin. After correction of spot volumes by total protein
      concentrations, 10 spots derived from albumin, cytokeratin type II and alpha1
      antitrypsin remained significantly increased. CONCLUSION: The proteomic
      composition of AH differed significantly between patients and controls. The
      identified proteins suggest that the changes in AH are due to at least three
      different mechanisms: breakdown of the aqueous-blood barrier, enzymatic
      degradation, and liberation of locally synthesized proteins.

PMID- 15715555
TI  - Laser in situ keratomileusis for different degrees of myopia.
AB  - PURPOSE: To determine the efficacy, predictability, stability and safety of laser
      in situ keratomileusis (LASIK) in treating patients with different degrees of
      myopia. METHODS: We enrolled 386 eyes of 200 consecutive patients who underwent
      LASIK and divided them into four groups according to their degree of preoperative
      spherical equivalent (SE). Group 1 eyes ranged between - 1.00 and - 3.99 dioptres
      (D) (low myopia). Group 2 eyes ranged between - 4.00 and - 5.99 D (moderate
      myopia). Group 3 eyes ranged between - 6.00 and - 9.99 D (high myopia). Group 4
      eyes were over - 9.99 D (extreme myopia). Follow-up was at 1 day, 1 week and 1,
      3, 6, 12 and 18 months postoperatively. RESULTS: Our study included 386 eyes of
      200 patients with SE ranging from - 3.00 to - 16.00 D (mean - 7.14 +/- 2.87 D).
      All eyes were seen at 1 day postoperatively. A total of 360 eyes (93%) were
      examined at 1 week, 330 eyes (85%) at 1 month, 281 eyes (73%) at 3 months, 247
      eyes (64%) at 6 months, 199 eyes (52%) at 12 months and 142 eyes (37%) at 18
      months. The postoperative data from 1 day to 12 months were used because of the
      low follow-up rate at 18 months postoperatively. Group 1 consisted of 30 eyes.
      The mean SE was - 3.52 +/- 0.43 D preoperatively and - 0.40 +/- 0.58 D at 1
      month, - 0.46 +/- 0.60 D at 6 months and - 0.42 +/- 0.50 D at 12 months
      postoperatively. Uncorrected visual acuity (UCVA) was 20/40 or better in 95% of
      eyes at 1 day and in 100% of eyes at 6 and 12 months postoperatively. Group 2
      consisted of 151 eyes. The mean SE was - 5.36 +/- 0.67 D preoperatively and -
      0.54 +/- 0.78 D at 1 month, - 0.56 +/- 0.90 D at 6 months and - 0.55 +/- 0.82 D
      at 12 months postoperatively. Uncorrected VA was 20/40 or better in 95% of eyes
      at 1 day and in 100% of eyes at 6 and 12 months postoperatively. Group 3
      consisted of 167 eyes. The mean SE was - 8.15 +/- 0.94 D preoperatively and -
      0.58 +/- 0.90 D at 1 month, - 0.67 +/- 1.00 D at 6 months and - 0.64 +/- 0.95 D
      at 12 months postoperatively. Uncorrected VA was 20/40 or better in 90% of eyes
      at 1 day and in 98% of eyes at 6 and 12 months postoperatively. Group 4 consisted
      of 38 eyes. The mean SE was - 11.09 +/- 1.10 D preoperatively and - 1.25 +/- 1.20
      D at 1 month, - 1.13 +/- 1.30 D at 6 months and - 1.20 +/- 1.25 D at 12 months
      postoperatively. Uncorrected VA was 20/40 or better in 78% of eyes at 1 day, in
      94% at 6 months and in 90% at 12 months postoperatively. Intraoperative
      complications (free cap) occurred in two eyes and postoperative complications
      were observed in three eyes, making the total complications rate 1.29% (5/386).
      Seven eyes lost one Snellen line of BCVA, five lost two lines and two lost more
      than two lines (total: 3.64%, 14/386). CONCLUSION: In conclusion, LASIK is
      effective, predictable and safe for correcting myopia but is more accurate for
      correcting myopia up to -10.00 D. With more improvement in algorithms and
      ablation profile, we believe that LASIK can offer better results for higher
      myopia.

PMID- 15715556
TI  - The Groningen Longitudinal Glaucoma Study. I. Baseline sensitivity and
      specificity of the frequency doubling perimeter and the GDx nerve fibre analyser.
AB  - PURPOSE: To describe the baseline data of a large cohort of patients included for
      follow-up with perimetry using the frequency doubling technique (FDT) and with
      quantification of the retinal nerve fibre layer as assessed by GDx, and to
      calculate the sensitivity and specificity of both devices from these baseline
      data. METHODS: Regular visitors to our glaucoma service were included. All
      subjects were followed for at least 4 years with FDT in full-threshold mode, GDx
      and conventional perimetry. Patients were classified as having either glaucoma or
      suspect glaucoma, according to baseline perimetry results. In addition, a group
      of healthy subjects was recruited outside the hospital. RESULTS: A total of 452
      glaucoma patients, 423 glaucoma suspects and 237 healthy subjects were
      incorporated into the analyses. Sensitivities for both FDT and GDx were fixed at
      0.90. For the group as a whole, the specificity was 0.81 for FDT, using number of
      depressed test-points p < 0.01 in the total deviation probability plot with a cut
      off point > 1, and 0.78 for GDx, using the Number, with a cut-off point > 29. The
      area under the receiver operating characteristic (ROC) curve was 0.92 for FDT and
      0.94 for GDx. Of the subjects with suspect glaucoma, 75% showed normal FDT test
      results and 52% showed normal GDx results. Unlike FDT, GDx failed to detect some
      moderate/severe glaucoma cases. CONCLUSIONS: The performances of FDT and GDx are
      approximately equivalent in terms of sensitivity, specificity and area under the
      ROC curve. In glaucoma suspects, GDx in particular yielded a rather high
      percentage of positive test results. The majority of these positive test results
      are presumably false-positive results rather than results indicating
      preperimetric glaucoma.

PMID- 15715557
TI  - Strategies for improving the diagnostic specificity of the frequency doubling
      perimeter.
AB  - PURPOSE: To evaluate various strategies designed to improve the specificity of
      the interpretation of results obtained with the frequency doubling technology
      perimeter (FDT) used in the full-threshold mode. METHODS: Three different
      strategies were compared using data from 452 glaucoma patients and 237 healthy
      subjects: combining several FDT parameters from a single test, combining the FDT
      test with a GDx test, and confirming an abnormal FDT test result with a repeat
      test. RESULTS: Confirming an abnormal FDT test result with a repeat test yielded
      a specificity increase of 0.10, from 0.80 to 0.90, at the expense of some loss of
      sensitivity for early but not for moderate or severe glaucoma. Combining several
      FDT parameters from a single test and combining FDT with GDx did not yield any
      noticeable increase in diagnostic performance. CONCLUSIONS: A modest increase in
      FDT diagnostic performance can be obtained by the confirmation of an abnormal
      test result with a repeat test.

PMID- 15715558
TI  - Vasoactive mediators and retinopathy during type 1 diabetic pregnancy.
AB  - PURPOSE: To evaluate the role of various vasoactive hormones in the evolution of
      diabetic retinopathy during pregnancy and postpartum. METHODS: Retinopathy was
      graded from fundus photographs of 45 pregnant women with type 1 diabetes and
      seven pregnant women without diabetes in a prospective study. Markers of renin
      angiotensin-system (RAS), plasma renin activity (PRA), angiotensin II (AngII),
      aldosterone, natriuretic peptides (ANP, BNP, CNP) and adreonomedullin (AM) were
      measured during the first and third trimesters and at 3 months postpartum. The
      women with diabetes were grouped by progression of retinopathy during pregnancy
      and postpartum. RESULTS: Levels of PRA (p = 0.001) and ANP (p = 0.03) were
      significantly lower in diabetes than in non-diabetes subjects throughout
      pregnancy and postpartum. No significant differences appeared in levels of AngII,
      aldosterone, AM, BNP or CNP between the two groups. In multivariate logistic
      regression analyses with retinopathy progression by the third trimester as the
      dependent variable, only duration of diabetes qualified in the model (p = 0.027,
      R = 0.227, Exp(B) = 1.28). CONCLUSIONS: Diabetic pregnancy is associated with
      lower levels of PRA and ANP compared to non-diabetic pregnancy. Lowered RAS
      activity may contribute to the hyperdynamic blood flow and progression of DR
      during diabetic pregnancy. Within the power of this study no clear associations
      between the vasoactive hormones and progression of retinopathy could be detected.

PMID- 15715559
TI  - Serous macular detachment in diabetic cystoid macular oedema.
AB  - PURPOSE: To define serous macular detachment in patients with diabetic cystoid
      macular oedema (CME). METHODS: This study involved 78 eyes of 58 patients with
      diabetic CME. The patients underwent complete ophthalmic examination, fluorescein
      angiography and optical coherence tomography (OCT). Eyes with epiretinal membrane
      or vitreo-macular traction were not included in the study. Optical coherence
      tomography-3 was used in all patients and fundi were scanned on the horizontal,
      vertical and four oblique planes through the centre of the fovea. RESULTS: In all
      cases the increased thickness of the retina was related primarily to the
      hyporeflective intraretinal cavities. With OCT, 24 of 78 eyes (31%) had serous
      macular detachment as shown by retinal elevation over a non-reflective cavity
      with minimal shadowing of the underlying tissues. Fluorescein angiography did not
      show serous macular detachment in any patient. CONCLUSIONS: Our data showed that
      the incidence of serous macular detachment in diabetic CME was much higher than
      previously reported. Optical coherence tomography-3 allows an in vivo cross
      sectional observation of very subtle serous macular detachment that is difficult
      to diagnose at the slit-lamp or by fluorescein angiography in patients with
      diabetic CME.

PMID- 15715560
TI  - Intravitreal triamcinolone for macular oedema: efficacy in relation to aetiology.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal triamcinolone in
      patients with macular oedema of varying aetiology. METHODS: Two milligrams of
      intravitreal triamcinolone acetonide was injected into 34 eyes with persistent
      macular oedema (17 eyes with macula oedema secondary to posterior uveitis, 13
      eyes with diabetic retinopathy, and four with pseudophakic macular oedema). Best
      corrected visual acuity was determined and transfoveal optical coherence
      tomography performed after 1 week, 1 month, 3 months and 6 months. RESULTS:
      Treatment improved visual acuity and subjective visual quality, and reduced
      foveal thickness in eyes with posterior uveitis and eyes with macular oedema
      secondary to diabetic retinopathy. Eyes treated for pseudophakic cystoid macular
      oedema demonstrated no improvement. A total of 32% of patients experienced a
      significant post-injection increase in intraocular pressure. Endophthalmitis,
      rhegmatogenous retinal detachment and cataract were absent. CONCLUSION:
      Intravitreal triamcinolone appears to induce marked a improvement in macular
      oedema secondary to non-infectious uveitis and diabetic retinopathy.

PMID- 15715561
TI  - Intravitreal triamcinolone acetonide in patients with macular oedema due to
      central retinal vein occlusion.
AB  - PURPOSE: To evaluate treatment of macular oedema due to central retinal vein
      occlusion (CRVO) with intravitreal triamcinolone acetonide. METHODS: In a
      prospective case series, 13 patients with macular oedema due to non-ischaemic
      CRVO received an intravitreal injection of 4 mg triamcinolone acetonide.
      Examination included assessment of best corrected visual acuity (BCVA) for
      distance and reading, measurement of intraocular pressure (IOP), fluorescein
      angiography and high resolution imaging by optical coherence tomography,
      preoperatively and 1 week, 1 month, 3, 6 and 9 months postoperatively. RESULTS:
      Preoperative mean BCVA was 0.9 +/- 0.4 for distance vision and 1.0 +/- 0.3 for
      reading acuity, respectively. A significant improvement in distance VA (0.5 +/-
      0.3, p < 0.001) and reading acuity (0.7 +/- 0.3, p = 0.03) was observed until 3
      months and 6 months, respectively. Mean macular thickness was significantly
      reduced until 9 months postoperatively. CONCLUSION: Intravitreal injection of
      triamcinolone acetonide led to a significant improvement in mean VA in patients
      with macular oedema due to CRVO. However, the significant effect was not
      permanent and persisted for a maximum of 6 months.

PMID- 15715562
TI  - Is vision screening in 3-year-old children feasible? Comparison between the Lea
      Symbol chart and the HVOT (LM) chart.
AB  - PURPOSE: The aim of this prospective study was to compare visual screening at the
      age of 3 years with screening at 4 years using two different charts. METHODS: A
      total of 478 3-year-old children were tested at four child health care centres
      (CHCCs). Of these children, 440 were tested again at the age of 4 years. A third
      group, a control group, consisting of 229 children, was examined only at the age
      of 4 years. All children were tested with both the HVOT chart and the Lea Symbol
      chart. RESULTS: Testability rates for 3-year-olds were almost the same with the
      Lea Symbol chart and the HVOT chart (82.8% and 84.8%, respectively). The
      corresponding rates for the same children tested at 4 years of age were 96.5% and
      97.0%, and for the 4-year-olds not previously tested 92.9% and 92.8%. The mean
      testing time was somewhat shorter for the Lea Symbol chart in all three groups,
      but the difference was not statistically significant. The difference in the
      assessment of visual acuity between the two charts was small and less than 1/10th
      of a line. The positive predictive value was lower at 3 years (58%) than has
      previously been found at 4 years (74.6%). CONCLUSION: Three-year-old children co
      operate well in visual acuity testing. However, the examination time is a little
      longer and the testability rate is about 10% lower than at 4 years. Both 3-year
      old and 4-year-old children can be tested equally well with the HVOT and the Lea
      Symbol charts.

PMID- 15715563
TI  - Reduction of asthenopia related to accommodative relaxation by means of far point
      stimuli.
AB  - PURPOSE: To conduct an experimental investigation of the effect of accommodative
      relaxation using far point shift stimuli for the reduction of asthenopia.
      METHODS: Twenty-two female students accommodated to a far point shift stimuli
      during a 2-min period immediately after a 15-min sustained task on a three
      dimensional display. Before and after the trial, their accommodative step
      response and symptoms were assessed. The far point shift stimuli in the optical
      system, which were presented on a refractometer, were created by moving the
      target scenery images from far to near, lineally centred about the far point
      position of each eye. During 2 min of fixating on the far point shift stimuli,
      changes in refraction were recorded in the same eye. RESULTS: While looking at
      the far point shift stimuli, 10 of 22 subjects had changes in refraction that
      showed a hypermetropic shift, and the other 12 subjects had changes in refraction
      that showed a myopic shift. The time taken for the accommodative step response
      from far to near post-trial in the myopic shift group was markedly prolonged, and
      the accommodative lag at the far target in the optometer was significantly
      increased. In the myopic shift group, the symptoms of "eye fatigue", "eye pain",
      "eye heaviness", and "eye dryness" also increased after the trial. In the
      hyperopic shift group, however, only the symptom of "eye dryness" increased, with
      no reduction of accommodation function. CONCLUSIONS: We suggest that
      accommodative relaxation by accommodative far point shift stimuli is effective in
      the reduction of asthenopia.

PMID- 15715564
TI  - A comparison of colour micrographs obtained with a charged couple device (CCD)
      camera and a 35-mm camera.
AB  - PURPOSE: The purpose of this study was to determine if micrographs produced with
      a colour charged couple device (CCD) camera were comparable in quality to
      micrographs obtained with a 35-mm colour film camera. The Axiocam (Zeiss, Jena,
      Germany) CCD camera produced images of 3900 x 3090 pixels. METHODS: Each picture
      in a series of 50 pairs of film and digital micrographs was rated independently
      by each of three observers on the categories of colour, detail and overall
      impression. A total of 28 of the 50 pairs of micrographs were discarded due to
      colour differences. RESULTS: Digital micrographs were rated lower on colour and
      higher on detail compared to film micrographs. The film and digital micrographs
      were rated equally on overall impression. The difference in colour between film
      and digital micrographs can be compensated for using image processing software on
      the digital image. However, such manipulation was not carried out as part of the
      present study. The study originally included 50 digital micrographs and 50 film
      micrographs. The micrographs were paired and 22 of the 50 pairs of micrographs
      were assessed. Thus 28 pairs were not evaluated due to colour differences in the
      non-manipulated pictures. The interobserver difference on colour in the remaining
      22 pairs given as mean square +/- standard error of the mean was - 0.27 +/- 0.10,
      0.62 +/- 0.10 and 0.90 +/- 0.11. The interobserver difference on detail was -
      0.48 +/- 0.10, 0.95 +/- 0.10 and 1.43 +/- 0.10. The interobserver difference on
      overall impression was - 0.70 +/- 0.10, 0.57 +/- 0.10 and 1.27 +/- 0.10. All the
      results differed significantly (p < 0.001). CONCLUSION: Digital micrographs are
      sufficient in detail, colour and overall impression to replace the traditional 35
      mm film recordings for use in histopathology.

PMID- 15715565
TI  - Lesions of the lacrimal drainage system: a clinicopathological study of 643
      biopsy specimens of the lacrimal drainage system in Denmark 1910-1999.
AB  - PURPOSE: To determine the frequency of histologically verified lesions of the
      lacrimal drainage system in Denmark between the years 1910 and 1999. Furthermore,
      to correlate the clinical diagnosis with the pathology diagnosis. METHODS:
      Retrospective review of all pathology reports from 1910 to 1999 in the files of
      the Eye Pathology Institute, University of Copenhagen, describing a lesion of the
      lacrimal drainage system. In addition, a retrospective review of all reports
      describing a lesion of the lacrimal drainage system from the Danish Pathology
      Database. All specimens were re-evaluated, except in cases with a primary
      diagnosis of dacryocystitis. In these cases a sample of 25% was re-evaluated.
      RESULTS: A total of 643 lesions were collected. Dacryocystitis was the most
      frequent lesion, constituting 508 cases (79%). The remaining cases were diagnosed
      as dacryolithiasis (62 cases; 7.9%), tumour (29 cases; 4.5%), trauma (19 cases;
      3.0%), congenital malformation (nine cases; 1.4%), canaliculitis (eight cases;
      1.2%) and granulomatous inflammation (eight cases; 1.2%). Seventeen tumours were
      malignant, of which B-cell lymphoma was the most common (six cases). In 0.6% of
      cases with a clinical diagnosis of dacryocystitis/lithiasis a non-suspected
      malignant tumour was diagnosed. Micro-organisms were uncommon in dacryocystitis
      (9%) but frequent in cases of dacryolithiasis (87%). CONCLUSION: Dacryocystitis
      was by far the most frequent lesion of the lacrimal drainage system referred for
      histopathological evaluation. Dacryolithiasis was often associated with micro
      organisms, especially Gram positive rods. Histopathology is necessary to confirm
      suspected tumours, more than half of which were inflammatory lesions, and to
      detect tumours that sometimes masquerade as inflammation.

PMID- 15715566
TI  - Occurrence of lacrimal gland tissue outside the lacrimal fossa: comparison of
      clinical and histopathological findings.
AB  - PURPOSE: To analyse clinical referral diagnoses and the location of lesions with
      histologically verified lacrimal gland tissue occurring outside the fossa of the
      lacrimal gland. METHODS: Sections of lesions excised from areas outside the fossa
      of the lacrimal gland containing lacrimal gland tissue on histological
      examination were collected from the files of the Eye Pathology Institute,
      Copenhagen, Denmark. Specimens spanned a period of 50 years. Sections were re
      examined and referral data on location and clinical diagnosis were compared with
      histological findings. RESULTS: A total of 120 lesions were collected. Of these,
      59 (49%) consisted of prolapsed lacrimal gland. The remaining 61 (51%) lesions
      contained ectopic lacrimal gland tissue, either as part of a complex choristoma
      in 38 (32%) cases, or as solitary ectopic lacrimal gland tissue in 23 (19%)
      cases. The majority (97; 81%) of lesions had been located at the temporal
      epibulbar conjunctiva and included mainly prolapsed lacrimal gland and complex
      choristoma. The clinical referral diagnoses covered a wide spectrum of lesions.
      The most frequent clinical diagnoses were non-specific tumour (35%), non-specific
      cyst (18%) and dermoid (11%). Of the 61 lesions containing ectopic lacrimal gland
      tissue, only two had been preoperatively diagnosed as such and only two of the 59
      lesions with prolapsed lacrimal gland had been correctly diagnosed. CONCLUSIONS:
      Prolapsed palpebral lobe of the lacrimal gland was the most common lesion and, as
      expected, the prime location was the temporal conjunctiva. Despite this location,
      the referring clinical diagnosis was often wrong or non-specific. Surgeons seem
      to have been unaware of the various clinical manifestations of extrafossal
      glandular tissue, particularly when excising lesions in the upper temporal region
      of the conjunctiva. Surgical intervention in this location may jeopardize the
      excretory ducts of the lacrimal gland and may consequently lead to dry eye and
      thus should be avoided when the typical clinical appearance of prolapsed lacrimal
      gland is encountered.

PMID- 15715567
TI  - Effects of interleukin-1beta and dexamethasone on the expression of matrix
      metalloprotease mRNA by trabecular cells exposed to elevated hydrostatic
      pressure.
AB  - PURPOSE: We investigated the effects of interleukin-1beta (Il-1beta) and
      dexamethasone (Dex) on the expression of matrix metalloprotease-1, -2, -3 and -14
      (membrane type-1 MMP-MT1-MMP) as well as tissue inhibitors of matrix
      metalloproteases (TIMP-1 and -2) mRNA by trabecular cells exposed not only to
      normal, but also to elevated levels of hydrostatic pressure. METHODS: Confluent
      primary cultures of porcine trabecular cells were incubated in a serum-free
      medium (SFM) as controls, or in SFM containing either 10 ng/ml Il-1beta or 10 nm
      Dex and exposed to pressures of 15 mmHg or 50 mmHg (corresponding to normal and
      high intraocular pressure, respectively) in specially designed pressure chambers.
      After 72 hours, total RNA was extracted from the harvested cells, reverse
      transcribed and amplified using primers specific to MMP-1, -2, -3 and -14, and
      TIMP-1 and -2. RESULTS: The most significant changes were detected in the levels
      of MMP-3 mRNA in control cells (2.4-fold increase), of TIMP-1 and -2 mRNA in
      cells treated with Il-1beta (2.6-fold increase) and of MMP-3 mRNA in cells
      treated with Dex (3.5-fold increase) exposed to 50 mmHg pressure. CONCLUSION:
      Because MMP-3 (stromelysin) mRNA showed the highest upregulation, our findings
      suggest that trabecular cells preferentially degrade and turn over the
      proteoglycan components of the extracellular matrix in response to short-term
      exposure to increased hydrostatic pressure with and without Dex as a homeostatic
      mechanism.

PMID- 15715568
TI  - Malignant melanoma of the choroid associated with misdiagnosed ocular
      melanocytosis.

PMID- 15715569
TI  - Total iris expulsion through a sutureless cataract incision due to vomiting.
AB  - PURPOSE: To present a case of isolated total iris expulsion through a self
      sealing cataract incision 2 weeks postoperatively due to vomiting. METHODS:
      Ophthalmological examination included visual acuity assessment, tonometry, slit
      lamp examination, fundus ophthalmoscopy and ultrasound examination. RESULTS: A 65
      year-old woman experienced sudden visual loss during an episode of vigorous
      vomiting 2 weeks after uncomplicated phacoemulsification cataract surgery with a
      sutureless corneal incision. Clinical examination showed a dense anterior chamber
      haemorrhage. When the blood had cleared, isolated total aniridia was seen.
      CONCLUSIONS: This is the first reported case of aniridia after cataract surgery
      due to vomiting.

PMID- 15715570
TI  - A case of Chandler's syndrome revealed by ultrastructural studies of the
      trabecular meshwork.
AB  - PURPOSE: To investigate ultrastructural changes in the aqueous outflow route and
      discuss the mechanisms associated with intraocular pressure (IOP) elevation in a
      patient with presumably early stage Chandler's syndrome. METHODS: A 47-year-old
      man underwent trabeculectomy because of elevated IOP. A specimen obtained during
      surgery was studied by transmission electron microscopy. RESULTS: Electron
      microscopy showed the presence of a monolayer composed of corneal endothelium
      like cells and thick basement membrane-like material. Neovascularization was also
      observed in the corneoscleral trabeculum. CONCLUSIONS: Our results indicate that
      several mechanisms, including the formation of basement membrane-like tissue,
      infiltration of inflammatory cells and neovascularization, might contribute to
      the elevation of IOP in Chandler's syndrome. These may occur even when there is
      no history of conspicuous inflammatory reaction in the anterior ocular segments.

PMID- 15715571
TI  - Recurrent secondary frosted branch angiitis after toxoplasmosis vasculitis.
AB  - PURPOSE: To describe a case of recurrent frosted branch angiitis after treatment
      of ocular toxoplasmosis. METHODS: In a 6-year-old boy, we found perivascular,
      creamy, patchy, retinal sheathing in both eyes without any focal necrotizing
      retinochoroiditis or scarring. IgM antibodies for toxoplasma gondii were also
      found. The patient was treated with antitoxoplasmosis medication and a systemic
      steroid. RESULTS: Several years after treatment of the toxoplasmosis, frosted
      branch angiitis occurred twice without any retinal scarring or serological
      evidence of toxoplasmosis. After systemic steroid therapy, the angiitis improved
      without further complications. CONCLUSIONS: Toxoplasmic retinal vasculitis should
      be considered as a cause of frosted branch angiitis.

PMID- 15715572
TI  - Anterior segment anomaly on optical coherence tomography.

PMID- 15715573
TI  - Postoperative pain relief in vitreoretinal surgery with subtenon Bupivacaine
      0.75%.

PMID- 15715574
TI  - Simultaneous bilateral visual loss caused by rupture of retinal arterial
      macroaneurysms in a hypertensive patient.

PMID- 15715575
TI  - Late onset branch retinal artery occlusion following coronary angiography.

PMID- 15715576
TI  - An unusually longstanding, strictly ocular, limited form of Wegener's
      granulomatosis.

PMID- 15715577
TI  - Oncocytoma of the eyelid.

PMID- 15715578
TI  - Upper eyelid oedema from a dumbbell-shaped dermoid cyst.

PMID- 15715579
TI  - Quantitative correlation of elevated intraocular pressure with relative afferent
      pupillary defect change in unilateral glaucoma.

PMID- 15715580
TI  - Clinical alert: damage to Goldmann applanation tonometer tips.

PMID- 15715581
TI  - Unilateral optic neuropathy associated with sildenafil intake.

PMID- 15715582
TI  - Central serous chorioretinopathy following vitrectomy with intravitreal
      triamcinolone acetonide for diabetic macular oedema.

PMID- 15715583
TI  - Uveal melanoma in an 18-year-old African black man.

PMID- 15715585
TI  - The epidemiology of preterm labour.
AB  - Although the definition of preterm birth is birth before 37 completed weeks, the
      major transition in terms of needing special care occurs between 34 and 37 weeks.
      The Homo sapiens neonate is born much more immature than other anthropoid
      species, perhaps because earlier birth has evolved to avoid the large head of the
      human fetus becoming impacted in the small pelvis of the mother, who has become
      adapted to a bipedal gait. The main burden of preterm birth exists in developing
      countries. There are no accurate recent worldwide data, but estimates of preterm
      birth rates range from 5% in developed countries to 25% in developing countries.
      The preterm delivery rate has been relatively stable at 5-10% in developed
      countries for many years. The North Thames database of 517,381 pregnancies
      demonstrates significant ethnic variation in preterm birth rates, with higher
      rates in black women. This is associated with an accelerated rate of maturity in
      the black fetus and neonate, with correspondingly lower gestation-specific
      neonatal mortality rates below 38 weeks, and higher at 38 weeks of gestation and
      beyond. Ethnic differences can explain only a very small proportion of global
      preterm births. The greatest aetiological factor worldwide is infection, mainly
      due to malaria and HIV. In developed countries, iatrogenic delivery is
      responsible for almost half of the births between 28 and 35 weeks; hypertension
      and pre-eclampsia are the major pathologies. Other factors include multiple
      pregnancy, intrauterine growth restriction, maternal stress and heavy physical
      work.

PMID- 15715586
TI  - Lung and brain damage in preterm newborns, and their association with gestational
      age, prematurity subgroup, infection/inflammation and long term outcome.
AB  - Compared with those born at term, preterm newborns are at an increased risk of
      short term disorders of the lung (bronchopulmonary dysplasia; BPD) and the brain
      (white matter damage; WMD), and of long term developmental and pulmonary
      dysfunctions. Although all of these adverse outcomes are associated with low
      gestational age, brain, but not lung, damage appears to be associated with the
      prematurity subgroup [spontaneous preterm labour and/or preterm prelabour rupture
      of membranes (PPROM) vs pregnancy-induced hypertension (PIH)]. Part of the
      association between brain damage and prematurity subgroup might be due to a
      differential exposure of members of these subgroups to perinatal
      infection/inflammation. There is a lack of studies evaluating the association of
      antenatal and perinatal risk factors with late childhood pulmonary dysfunction
      among those born during the second trimester. In this paper we discuss the
      complexities that paediatricians, perinatologists and perinatal epidemiologists
      face as they try to understand the contributions of factors associated with
      preterm birth to neonatal and childhood disorders.

PMID- 15715587
TI  - The economic consequences of preterm birth during the first 10 years of life.
AB  - OBJECTIVE: To examine the association between gestational age at the time of
      birth and long-term use and cost of hospital inpatient services. DESIGN: Multi
      level modelling of the hospital service utilisation and cost profile of each
      child born in hospital during 1978-1988 in two areas covered by the Oxford Record
      Linkage Study. SETTING: Oxfordshire and West Berkshire. POPULATION: 117,212
      children divided into four subgroups by gestational age at birth: <28 weeks, 28
      31 weeks, 32-36 weeks, 37 weeks or greater. MAIN OUTCOME MEASURES: Number and
      duration of hospital admissions during the first 10 years of life. Costs,
      expressed in pound sterling and valued at 1998-1999 prices, of hospital inpatient
      services. RESULTS: The cumulative cost of hospital inpatient admissions incurred
      during the first 10 years of life, including the initial birth admission,
      averaged 17,819.94 [22,322.87 UK pounds] for children born at <28 weeks
      gestation, 17,751.00 [19,055.53 UK pounds] for children born at 28-31 weeks
      gestation, 5,376.39 [7,393.78 UK pounds] for children born at 32-36 weeks
      gestation, and 1,658.63 [3,409.14 UK pounds] for children born at 37 weeks
      gestation or greater. The adjusted number of hospital inpatient admissions,
      inpatient days and costs, respectively, over the first 10 years of life was 130%,
      77% and 443% higher for children born at <28 weeks gestation than for children
      born at term. CONCLUSION: The adverse sequelae of preterm birth are likely to
      have considerable long-term economic consequences for the health services and for
      society as a whole.

PMID- 15715588
TI  - Role of cytokines in preterm labour and brain injury.
AB  - Intrauterine infection induces an intra-amniotic inflammatory response involving
      the activation of a number of cytokines and chemokines which, in turn, may
      trigger preterm contractions, cervical ripening and rupture of the membranes.
      Infection and cytokine-mediated inflammation appear to play a prominent role in
      preterm birth at early gestations (<30 weeks). The role of infection/inflammation
      in preterm birth in Europe has been incompletely characterised. The rate of
      preterm birth in Sweden is lower, and the rate of chorioamnionitis, bacterial
      vaginosis (BV), neonatal sepsis, and urinary tract infections during pregnancy is
      lower compared with the USA. In a Swedish population of women with preterm labour
      or preterm premature rupture of the membranes (PPROM) <34 weeks of gestation,
      microorganisms were detected in the amniotic fluid in 25% of women with PPROM and
      in 16% of those in preterm labour. Nearly half of these women had intra-amniotic
      inflammation defined as elevated interleukin-6 (IL-6) and IL-8, and there was a
      high degree of correlation between cytokine levels and preterm birth or the
      presence of microbial colonisation. These data do not support the hypothesis that
      infection-related preterm birth is less frequent in northern Europe than
      elsewhere. The intra-amniotic inflammatory response has also been associated with
      white matter injury and cerebral palsy. We find that in experimental models,
      induction of a systemic inflammatory response using lipopolysaccharide activates
      toll-like receptors (TLRs), which produce either white matter lesions or increase
      brain susceptibility to secondary insults. Recently, IL-18 in umbilical blood was
      shown to correlate with brain injury in preterm infants and IL-18 deficiency in
      mice decreases CNS vulnerability.

PMID- 15715589
TI  - Role of matrix metalloproteinases in preterm labour.
AB  - Extracellular matrix homeostasis is a key process in the maintenance of the
      tensile strength of the amniochorion. This tensile strength guarantees the role
      of the membranes as a physical and functional boundary for the fetus during human
      pregnancy. Pathological rupture of these structures before 37 completed weeks of
      gestation is known as preterm prelabour rupture of the membranes (PPROM) and it
      is a major cause of spontaneous preterm labour and preterm birth. A mechanism
      involving the activation of matrix metalloproteinases (MMP)-9, a 92-kDa type IV
      collagenase, as an essential mediator of tissue damage is under investigation.
      The proposed mechanism involves the abnormal expression and activity of MMP-9
      with subsequent connective tissue degradation taking place at a time that does
      not synchronise with other events of labour. The local physiological signal by
      amniochorion cells to induce MMP-9 expression is not known, but bacterial
      products and/or the proinflammatory cytokines, IL-1beta and TNF-alpha, as
      paracrine or autocrine signals may trigger these processes in pregnancies
      complicated with intra-amniotic infection. These signalling pathways indicate
      complex cooperative and bidirectional communications between amnion and
      choriodecidua in response to bacterial products, which include intermembranous
      cytokine traffic and signalling between tissues. Products secreted in culture by
      amniochorion and choriodecidual leucocytes, obtained from women who delivered
      following normal labour in the absence of infection, condition a specific
      microenvironment that induces collagen degradation in fetal membranes. Further
      characterisation of the role of choriodecidual leucocytes in the control of
      extracellular matrix degradation in amniochorion is currently under way.

PMID- 15715590
TI  - Changes in the cervical competence in preterm labour.
AB  - Cervical competence is a key function in normal and abnormal labour. Remodelling
      of the cervical structure, by reorientation and changes in the integrity of
      collagen fibres by an alteration in the content of water, proteoglycans and
      hyaluronic acid, takes place before parturition. Such morphological changes have
      been associated with the activation of several biochemical pathways, sharing
      those of an apyretic, proinflammatory reaction, including the inducible isoform
      of the nitric oxide synthase (NOS). Nitric oxide (NO) is believed to be the final
      mediator in the mechanisms that allow ripening of the cervix. A reduction of NO
      activity in the uterus, together with its activation in the cervix, is
      hypothesised to be a facilitating factor in human parturition. The local
      application of NO donors in both animals and humans induces ultrastructural
      changes similar to those occurring during physiological cervical maturation. NO
      donors have proven to be clinically effective in facilitating first trimester
      dilation and curettage. Preliminary data also suggest that in women presenting
      with threatening preterm labour, there is increased activity of NO in the cervix,
      which is associated with shortening. A complex interaction between cytokines,
      prostaglandins (PGs) and NO is the key biochemical pathway accounting for the
      preterm ripening of the cervix.

PMID- 15715591
TI  - Current understanding of genetic factors in preterm birth.
AB  - Several lines of evidence support a genetic predisposition to spontaneous preterm
      labour and preterm birth. Firstly, a leading risk factor for spontaneous preterm
      labour and preterm birth is a personal or family history. If a woman previously
      delivered preterm, her subsequent babies are also more likely to be born preterm.
      Women who experienced an early preterm birth (<32 completed weeks) in their first
      pregnancy have the highest rate of recurrent preterm birth in subsequent
      pregnancies. Spontaneous preterm labour and preterm birth in subsequent
      pregnancies tend to recur at equivalent gestational ages. If a woman herself was
      born preterm, she is also at an increased risk of spontaneous preterm labour and
      preterm birth, with the risks being highest for those women who themselves were
      born most preterm. This predisposition does not apply to men who were born
      preterm. Racial predispositions to preterm birth have also been observed. Black
      women suffer twice the rate of preterm birth compared with Caucasians, even when
      confounding social and economic variables are controlled. It is well established
      that upper genital tract infection and/or inflammation is seen in association
      with spontaneous preterm labour and preterm birth. Previous investigations have
      focussed primarily on an infectious aetiology for this finding. However, an
      alternative hypothesis has emerged, which suggests that this finding may
      represent an abnormal inflammatory response. The frequent association of
      spontaneous preterm labour and preterm birth with histological
      infection/inflammation and elevated body fluid concentrations of inflammatory
      cytokines has focussed investigations on single gene polymorphisms of these
      cytokines in both mother and fetus. The polymorphisms tumour necrosis factor
      alpha-308 (TNF-alpha-308), interleukin-1beta (IL-1beta) + 3953/3954 and IL-6-174
      have been most consistently associated with spontaneous preterm labour and
      preterm birth. Toll-like receptors (TLRs) are important components of the innate
      immune systems, which have also been linked to spontaneous preterm labour and
      preterm birth. Both maternal and fetal polymorphisms of the TLR-4 gene have been
      associated with spontaneous preterm labour and preterm birth in certain
      populations, but in others no apparent link has been observed. These findings
      confirm a clear genetic predisposition to spontaneous preterm labour and preterm
      birth and raise hopes that patient-specific therapies may be developed in the
      future.

PMID- 15715592
TI  - Preterm premature rupture of membranes: diagnosis, evaluation and management
      strategies.
AB  - Preterm premature rupture of the membranes (PPROM) is responsible for one-third
      of all preterm births and affects 120,000 pregnancies in the United States each
      year. Effective treatment relies on accurate diagnosis and is gestational age
      dependent. The diagnosis of PPROM is made by a combination of clinical suspicion,
      patient history and some simple tests. PPROM is associated with significant
      maternal and neonatal morbidity and mortality from infection, umbilical cord
      compression, placental abruption and preterm birth. Subclinical intrauterine
      infection has been implicated as a major aetiological factor in the pathogenesis
      and subsequent maternal and neonatal morbidity associated with PPROM. The
      frequency of positive cultures obtained by transabdominal amniocentesis at the
      time of presentation with PPROM in the absence of labour is 25-40%. The majority
      of amniotic fluid infection in the setting of PPROM does not produce the signs
      and symptoms traditionally used as diagnostic criteria for clinical
      chorioamnionitis. Any evidence of infection by amniocentesis should be considered
      carefully as an indication for delivery. Documentation of amniotic fluid
      infection in women who present with PPROM enables us to triage our therapeutic
      decision making rationally. In PPROM, the optimal interval for delivery occurs
      when the risks of immaturity are outweighed by the risks of pregnancy
      prolongation (infection, abruption and cord accident). Lung maturity assessment
      may be a useful guide when planning delivery in the 32- to 34-week interval. A
      gestational age approach to therapy is important and should be adjusted for each
      hospital's neonatal intensive care unit. Antenatal antibiotics and corticosteroid
      therapies have clear benefits and should be offered to all women without
      contraindications. During conservative management, women should be monitored
      closely for placental abruption, infection, labour and a non-reassuring fetal
      status. Women with PPROM after 32 weeks of gestation should be considered for
      delivery, and after 34 weeks the benefits of delivery clearly outweigh the risks.

PMID- 15715593
TI  - Primary predictors of preterm labour.
AB  - Spontaneous preterm birth accounts for 60% of all preterm births in developed
      countries. With the increase in multiple pregnancies, induced preterm birth and
      the progress in neonatal care for extremely preterm neonates, spontaneous preterm
      birth for singleton pregnancies in developed countries has probably decreased
      over the past 30 years. This decrease is likely to be related to better prenatal
      care for all pregnant women because the recognition of primary risk factors in
      early or late pregnancy remains a basic part of prenatal care. The failure to
      distinguish between induced and spontaneous preterm labour in most population
      based studies makes it difficult to interpret results with respect to the primary
      predictors of preterm labour. Many such primary predictors of preterm labour have
      been used over the past 20-30 years. These include individual factors, socio
      economic factors, working conditions and obstetric and gynaecological history.
      Risk scores have been proposed in order to produce these data. Unfortunately, the
      predictive value of these scores, especially their specificity, is poor, mainly
      because all of these factors are indirect. We still cannot identify the
      mechanisms that lead to preterm labour and birth. New markers more directly
      related to preterm labour have recently been proposed, some of which relate to
      direct causes of preterm labour such as cervical ultrasound measurement, fetal
      fibronectin (FFN), salivary estriol, serum CRH and bacterial vaginosis. Several
      of these have predictive values, which are potentially useful for clinical
      practice. Nonetheless, pregnant women in developed countries are already closely
      monitored throughout pregnancy. Before proposing new screening tests to be
      applied systematically to all pregnant women, their advantages and drawbacks must
      be fully evaluated.

PMID- 15715594
TI  - Secondary predictors of preterm labour.
AB  - In addition to primary predictors of preterm birth which are used to estimate the
      baseline risk of preterm birth, secondary predictors (based on examinations done
      during the current pregnancy) allow a more accurate assessment of the risk of
      preterm birth in individual women. Screening for early signs of spontaneous
      preterm labour has always been an important topic in obstetric care. During the
      last two decades, the detection of fetal fibronectin (FFN) from cervicovaginal
      secretions and cervical shortening diagnosed by transvaginal ultrasonography have
      emerged as the major secondary predictors of preterm birth. Both markers have
      been extensively studied and consistently shown to be strong short term
      predictors of preterm birth across a wide range of gestational ages. Other
      secondary predictors that confirm the role of intrauterine infection in the
      pathogenesis of preterm birth are bacterial vaginosis (BV) and elevated levels of
      interleukin (IL)-6, IL-8, ferritin and granulocyte colony-stimulating factor.
      Apart from BV, inflammatory markers are still not routinely used. The sensitivity
      of single markers in predicting preterm birth is only moderate and serial
      examinations of markers, combinations of different markers and multiple marker
      tests have been studied, with limited results. Studies of interventions in order
      to prevent preterm birth have also yielded mixed benefits, as a consequence of
      which the use of these markers to screen low risk pregnancies is generally not
      recommended. Currently, secondary predictors of preterm birth are used mainly to
      design new intervention studies tailored to specific high risk populations and to
      avoid unnecessary interventions in the management of high risk women.

PMID- 15715595
TI  - Strategies for prevention--cervical cerclage.
AB  - Transvaginal cervical cerclage was introduced as a treatment for cervical
      incompetence in 1951. Over the years, our understanding of this clinical entity
      has changed tremendously, which has implications for obstetric management. This
      review focuses on the obstetric management of women considered to be at high risk
      of preterm delivery due to cervical incompetence at different stages of
      pregnancy.

PMID- 15715596
TI  - The changing role of progesterone in preterm labour.
AB  - Progesterone is an essential hormone in the process of reproduction. It is
      involved in the menstrual cycle, implantation and is essential for pregnancy
      maintenance. Although the pharmacokinetics and pharmacodynamics of progesterone
      have been well studied, and since 1935 it has been synthesised and is now
      available commercially, its use in the pathophysiology of pregnancy remains
      controversial. One of these concerns is the way in which the hormone is
      administered, with parenteral use proving the best way to obtain optimal plasma
      levels. Another concern is the paucity of randomised controlled trials and the
      different dosages and populations studied. As a result, the therapeutic
      application of progesterone in pregnancy is restricted to the prevention and
      treatment of threatened miscarriage, recurrent miscarriage and preterm birth.
      Progesterone is efficacious when continuation of pregnancy is hampered by
      immunological factors, luteinic and neuroendocrine deficiencies and myometrial
      hypercontractility. This may explain the reduction in the incidence of preterm
      birth in high risk pregnant women using high-dosage prophylactic progesterone.

PMID- 15715597
TI  - Controversies in diagnosis of preterm labour.
AB  - Despite scientific advances, efforts to prevent preterm birth can be
      disappointing. Obstetric care must focus on strategies to improve the outcome of
      preterm infants. The major goal is to delay preterm birth long enough to allow
      the transfer of women about to deliver preterm to a facility with a neonatal
      intensive care unit and to administer corticosteroids to enhance fetal lung
      maturation. A prerequisite for the success of this strategy is the reliable
      identification of women who will give birth preterm. Although symptoms of preterm
      labour strongly suggest preterm birth, contractions-even if combined with
      cervical effacement and dilation-do not reliably predict preterm birth. The
      diagnosis of true preterm labour that will eventually lead to preterm birth has
      been facilitated by the use of transvaginal cervical ultrasonography and by the
      detection of fetal fibronectin (FFN) in cervicovaginal secretions. The main
      clinical value of these tests is that preterm birth is very unlikely if the
      results of both tests are negative. This may help to avoid unnecessary transfer,
      hospitalisation and treatment of women with false preterm labour. The detection
      of phosphorylated insulin-like growth factor binding protein-1 in cervicovaginal
      secretions, or elevated levels of inflammatory markers, like interleukin-6,
      interleukin-8 and tumour necrosis factor-alpha (TNF-alpha), also predict preterm
      birth in symptomatic women. These markers, however, are not routinely used to
      predict preterm birth in women with symptoms of preterm labour.

PMID- 15715598
TI  - Management of the neonate at the limits of viability.
AB  - The active treatment of fetuses or neonates at the limits of viability is an
      ongoing debate for perinatal physicians. Although initiating intensive care at 26
      weeks is generally accepted, the gray zone of gestational ages at which
      aggressive perinatal care should be offered is less clear and ranges from 22 to
      25 weeks. The gray zone has remained rather unchanged over the last decade.
      Attitudes vary among different countries, centres and individuals. The benefit
      burden ratio of neonatal intensive care is balanced differently according to
      competing moral values. Several factors underlie the difficulty in approaches to
      management decisions. Neonates lack the capacity to make decisions and most
      parents ignore the complexity of care during and after hospitalisation. Parents
      have to be informed about the survival rates and the risks of long term
      disabilities, but accuracy for each individual baby is very weak. Outcome data
      are published many years after the intensive care period, and results about the
      prevalence of severe disabilities over time are conflicting and vary widely
      (ranging from 10% to 60%). Information about more subtle disabilities which only
      become apparent around school age is scarce. Data on the impact of the longer
      term outcomes of new strategies like developmental care approaches (Neonatal
      Individual Developmental Care Assessment Programme: NIDCAP) are still
      insufficient but could prove to be an important recent step in improving outcome
      in extremely immature babies.

PMID- 15715599
TI  - Can antibiotics prevent preterm birth--the pro and con debate.
AB  - Studies using different diagnostic methods and outcome parameters have used
      different antibiotics and dose/administration regimes to women of differing risk
      of preterm birth with, not surprisingly, different results. Studies which have
      shown benefit have been criticised for having either poor methodology, low sample
      size or having only showed benefit after a non-prespecified subgroup analysis.
      Studies which have failed to show any benefit have been criticised for
      unacceptable methods of diagnosing abnormal genital tract flora or having
      excluded a large percentage of patients eligible for the study, for having
      permitted a long period to elapse from diagnosis of abnormal genital tract flora
      to administration of treatment and for having employed treatment too late in
      pregnancy. A Cochrane Systematic Review of these studies failed to provide a
      definitive answer because this was published one month before two randomised
      double-blind placebo-controlled trials were published, in which clindamycin used
      either systemically or intravaginally in low risk, unselected women resulted in a
      60% reduction in the incidence of preterm birth. This would have influenced the
      inconclusive results of the Cochrane review, with respect to general population
      studies. Very early spontaneous preterm labour and preterm birth is more likely
      to be of infectious aetiology than preterm birth just before term. The earlier in
      pregnancy at which abnormal genital tract flora is detected, the greater is the
      risk of an adverse outcome. Women with abnormal flora in early pregnancy, who
      subsequently revert to normal, continue to have a high risk of adverse outcome of
      pregnancy, at a degree similar to women with abnormal genital tract flora in
      early pregnancy who were treated with placebo. This suggests that whatever damage
      abnormal flora induces, this is at an early gestation, even if the flora
      subsequently reverts to normal. It follows therefore that if antibiotics are to
      be of help in preventing spontaneous preterm labour and preterm birth of
      infectious aetiology, these must be administered early in pregnancy. Antibiotics
      used prophylactically for the prevention of preterm birth are more likely to be
      successful if: they are used in women with abnormal genital tract flora (rather
      than other risk factors for preterm birth, e.g. low BMI, twins, generic previous
      preterm birth); they are used early in pregnancy prior to infection (tissue
      penetration/inflammation and tissue damage); they are used in women with the
      greatest degree of abnormal genital tract flora; and if they are used in women
      with a predisposition to mount a damaging inflammatory response to infection.

PMID- 15715600
TI  - Adverse effects of tocolytic therapy.
AB  - The rationale for using tocolytics in preterm labour is to enable transfer of the
      mother to a tertiary centre and to prolong pregnancy sufficiently so that
      glucocorticoids can be administered to the mother. There is little question that
      these short term objectives can be achieved with contemporary tocolytics. Whether
      tocolytics can maintain pregnancy for sufficient periods to enable in utero
      maturation to occur remains an unresolved question. When a decision is made to
      use tocolytics, the clinician is faced with a multitude of choices with side
      effects, efficacy and ease of administration generally being the most important
      considerations. Placebo-controlled studies suggest that the beta-agonists,
      prostaglandin inhibitors and atosiban are effective in prolonging pregnancy for
      24-48 hours. Of these three agents, atosiban has the best safety profile. There
      are no placebo-controlled studies with calcium channel blockers or nitric oxide
      donors. However, because of their ease of use and efficacy compared with the beta
      agonists, calcium channel blockers are widely used. Calcium channel blockers
      appear to have a better safety profile than the beta-agonists, but there are
      still significant cardiovascular side effects associated with their use.
      Indomethacin, although proven to be efficacious, has a safety profile that limits
      its utility for other than short courses. Magnesium sulphate is the most commonly
      used tocolytic in the United States, despite a lack of evidence for its efficacy.
      Although magnesium sulphate appears to have a good safety profile, serious side
      effects have been reported with its use. The choice of tocolytics is commonly
      based on personal preference. Whichever tocolytic is chosen, the fundamental
      parturitional process is not reversed by contemporary treatment, rather a
      reduction in uterine response to a stimulant; thus, the expectations of tocolytic
      treatment need to be reconsidered.

PMID- 15715601
TI  - Nifedipine trials: effectiveness and safety aspects.
AB  - Nifedipine (Adalat) is marketed as an anti-hypertensive agent. Nifedipine
      inhibits voltage-dependent L-type calcium channels, which leads to vascular (and
      other) smooth muscle relaxation and negative inotropic and chronotropic effects
      on the heart. Vasodilation, followed by a baroreceptor-mediated increase in
      sympathetic tone then results in indirect cardiostimulation. Nifedipine was
      introduced as a tocolytic agent at a time when beta-agonists and magnesium
      sulphate dominated the arena for the prevention of preterm birth. The oral
      administration route, the availability of immediate and slow-release
      preparations, the low incidence of (mild) side effects, and its limited costs
      explain the attraction to this medication from the obstetric field and its rapid
      and widespread distribution. Currently, over 40 studies have been published on
      nifedipine's tocolytic effectiveness, including seven meta-analyses. The quality
      of the studies suffers particularly from performance bias because the majority of
      them failed to ensure adequate blinding to treatment both for providers and
      patients. Concerns about other methodological flaws include measurements, outcome
      assessment and attrition bias. In particular, the safety aspects of nifedipine
      for tocolysis have been under-assessed. Conclusions from the meta-analyses,
      favouring the use of nifedipine as a tocolytic agent, are not supported by close
      examination of the data. The tocolytic effectiveness and "safety" of nifedipine
      has been studied primarily in normal pregnancies. Based on its pharmacological
      properties, one should be cautious to administer nifedipine when the maternal
      cardiovascular condition is compromised, such as with intrauterine infection,
      twin pregnancy, maternal hypertension, cardiac disease, etc. Life-threatening
      pulmonary oedema and/or cardiac failure are definite risks and have been
      reported. Under such circumstances, the baroreceptor-mediated increase in
      sympathetic tone may not balance the cardiac-depressant activity of nifedipine.

PMID- 15715602
TI  - A review of the role for magnesium sulphate in preterm labour.
AB  - During the last decade, the body of medical knowledge concerning the use of
      pharmacological doses of magnesium sulphate (MgSO(4)) for preterm labour has
      increased substantially. Several randomised controlled trials (RCTs) have
      provided compelling evidence that MgSO(4) is the drug of choice for maternal
      seizure prophylaxis in pre-eclampsia, whether preterm or term. In contrast, a
      recent Cochrane systematic review of the relevant contemporary literature has
      found no evidence basis to support the use of MgSO(4) for tocolysis in preterm
      labour. Furthermore, associated with high-dosage tocolytic MgSO(4), recent data
      indicate a possible increased risk for neonatal intraventricular haemorrhage
      (IVH), as well as increased total paediatric mortality. It is possible, on the
      other hand, that the prophylactic administration of much lower dosages of
      MgSO(4), in selected cases of preterm labour, may have a neuroprotective effect
      for a small number of infants.

PMID- 15715603
TI  - Tocolytic therapy and clinical experience. Combination therapy.
AB  - OBJECTIVE: Inhibiting preterm labour at extremely early gestations. DESIGN:
      Observational study. Case reports. SETTING: Perinatal Centre Lund University
      Hospital, South Sweden. POPULATION: Twenty-five women (13 cases with intact
      membranes and 12 cases with ruptured) with threatened preterm labour and advanced
      cervical status before 26 completed weeks of gestation. METHODS: A combination of
      different drugs was used. Atosiban, an oxytocin antagonist, was the first line
      drug and was given as an infusion for several days as required. Supportive
      therapy was also given to most women with subcutaneous injections of the beta
      receptor agonist terbutaline (0.25 mg up to six times a day); sulindac, a
      prostaglandin synthetase inhibitor (200 mg one to two times a day up to a week);
      and broad-spectrum antibiotics (metronidazole and cefuroxime intravenously for
      three days and thereafter oral therapy). MAIN OUTCOME MEASURES: Prolongation of
      pregnancy more than 48 hours or 7 days. Neonatal survival. RESULTS: Prolongation
      of pregnancy for more than 48 hours to enable administration of corticosteroid
      therapy was obtained in all but three cases. Eight women were delivered after
      more than a week from admission. Three neonates died at birth due to obstetric
      complication or sepsis. The other neonates had normal pH in cord or venous blood
      at birth. No severe side effects were recorded and in no case did the treatment
      have to be discontinued due to side effects. CONCLUSION: The policy described
      here is not evidence based, relating only to clinical observations, and as such
      is of very limited value. However, it seems that with this combined approach to
      management, some days can be gained by achieving full effect of corticosteroid
      treatment and prolongation of the pregnancy, hopefully reducing time in the
      neonatal intensive care in these critical cases. No severe side effects were
      reported.

PMID- 15715604
TI  - Frequently asked questions on tocolytics.
AB  - The majority of drugs that are used today for tocolysis have been developed for
      clinical conditions other than preterm labour. Obstetricians started to use these
      drugs as tocolytics because of their additional influence on uterine smooth
      muscle relaxation, accepting their cardiovascular (side) effects. Because the
      majority of these drugs are used off label, today's strict criteria to evaluate
      drugs for their predominant use in pregnancy have not been applied; therefore, we
      also lack sufficient peri- and neonatal follow up data for these drugs. This
      problem is compounded as our understanding of the regulation of myometrial smooth
      muscle contraction and relaxation is still incomplete.

PMID- 15715605
TI  - Genetic factors in preterm birth--the future.
AB  - The genetic regulation of common biological functions has redundant control
      mechanisms, and it is unlikely that a single marker will ever be identified that
      will be both highly sensitive and specific. It is more likely that combinations
      of gene and/or protein markers, perhaps also combined with obstetric family
      histories, will be required to achieve the goal of a truly sensitive and specific
      screening profile for spontaneous preterm labour and preterm birth. The rapidly
      evolving disciplines of genomics and proteomics are now beginning to be applied
      to the study of spontaneous preterm labour and preterm birth. These techniques
      are able to measure multiple markers (in the thousands) in a biological sample
      and, given the likely presence of biological changes that precede by weeks or
      even months the clinical manifestations of the disease, are ideally suited to the
      evaluation of spontaneous preterm labour and preterm birth. Over the next few
      years, these technologies will hasten a deeper understanding of the
      pathophysiology of spontaneous preterm labour, discover novel target molecules
      and diagnostic biomarkers and ultimately aid in formulating more effective
      interventions to prevent preterm birth. Pharmacogenomics is another rapidly
      evolving discipline that holds great promise for the treatment and prevention of
      spontaneous preterm labour and preterm birth. Because spontaneous preterm labour
      is a final common pathway for multiple aetiologies, there remains no reason why
      any single therapy will work optimally for all women. As patient-specific
      pharmacogenomic profiles are developed, it will be possible to develop patient
      specific treatment regimens. Beyond that, it may become possible to identify
      those women who are, or are not, destined to labour spontaneously and give birth
      remote from term and to institute patient-specific preventive measures.
      Spontaneous preterm labour and preterm birth remains a syndrome, with a final
      common pathway for multiple aetiologies. As a result, no single explanation,
      marker or treatment is likely to be 100% sensitive, specific or successful. It is
      also clear, however, that there is a genetic predisposition in many cases of
      spontaneous preterm labour. Over the next few years, several recently developed
      diagnostic mechanisms, and others that have yet to evolve, will hold a greater
      potential than ever before to unlock the secrets of the genetic predisposition to
      spontaneous preterm labour and its underlying causes. An improved understanding
      of these mechanisms will allow clinicians to employ therapies that will be
      optimally effective for individual women and their unborn babies. Eventually,
      these advances could be applied to the presymptomatic prevention of spontaneous
      preterm labour. It is the intent of this manuscript to review the current status
      of these new technologies and disciplines and to speculate on their applications
      in the intermediate future.

PMID- 15715606
TI  - Use of uterine EMG and cervical LIF in monitoring pregnant patients.
AB  - OBJECTIVES: Review the uterine electromyography (EMG) and cervical light-induced
      fluorescence (LIF) devices and their role in the evaluation of uterine and
      cervical function in comparison with present methods. DESIGN: Review of recent
      studies. SETTING: University of Texas Medical Branch Labour and Delivery Clinics.
      POPULATION: Various groups of pregnant women. METHODS: We have developed and
      recently improved non-invasive methods to evaluate quantitatively uterine
      electrical signals from the abdominal surface and cervical collagen. MAIN OUTCOME
      MEASURES: Uterine EMG utilised power density spectrum (PDS) peak frequency and
      total power (P(0)) and cervical LIF utilising LIF ratio. RESULTS: Human studies
      indicate that uterine and cervical performance can be successfully monitored
      during pregnancy using EMG and LIF, respectively, and the assessment of uterine
      and cervical function can both be used to influence patient management in a
      variety of conditions associated with labour, more than can currently available
      methods. CONCLUSIONS: The potential benefits of the proposed instrumentation
      include the following: a reduction in the rate of preterm birth, improved
      maternal and perinatal outcome, better monitoring of treatment, decreased
      caesarean section rate and better research methods for understanding uterine and
      cervical function.

PMID- 15715607
TI  - The bioethics of preterm labour.
AB  - Until recently, bioethics (ethics related to biology or, more specifically, in
      the context of preterm labour, medical ethics) was considered mainly to relate to
      the active treatment or investigation of patients. Collection of data, excised
      specimens or even whole organs was considered to be relatively uncontentious as
      it did not impinge directly upon the health of the individual concerned. However,
      in the UK in particular, the practice of collecting data, tissues or even whole
      organs has recently come under the spotlight of public scrutiny, particularly
      following the Alder Hey Enquiry. Coincidentally with a decline in public
      confidence in the probity of authority, medical scientists increasingly have to
      justify the accumulation of data about individuals.

PMID- 15715608
TI  - Impact of medically assisted fertility on preterm birth.
AB  - Preterm birth is a frequent problem in women who undergo treatment for
      infertility. Many factors appear to contribute to the occurrence of this
      complication. Infertile women seem to have a predisposition to giving birth
      preterm and to having low birthweight babies. These complications also occur in
      women with a history of infertility who achieve pregnancy without treatment and
      who have singleton pregnancies. Assisted reproduction patients treated with in
      vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) have a
      disproportionately high occurrence of preterm births even with singleton
      pregnancies. Spontaneous preterm labour may be related to underlying medical
      conditions of the female partner, as its occurrence is not increased in subjects
      treated with ICSI (i.e. when the infertility problem is associated with male
      reproductive dysfunction in normal female partners). Multiple pregnancy is the
      factor most likely to be related to preterm birth in infertile women. The
      administration of drugs to induce ovulation either alone or combined with
      intrauterine insemination causes a significant increase in multiple pregnancies.
      The occurrence of higher order multiple pregnancy is also increased. Multiple
      pregnancy in women undergoing IVF or ICSI is related to the number of embryos
      transferred at the end of treatment. The transfer of more than two embryos in
      women under 35 is not associated with an increased chance of conception, while
      the occurrence of multiple pregnancy is significantly increased. Women over 40
      may benefit from the transfer of more than two embryos, with fewer risks of
      multiple pregnancy. Single embryo transfer is increasingly considered a workable
      clinical option, particularly in young women. Hopefully, a more cautious approach
      to infertility management will reduce the occurrence of multiple pregnancy,
      spontaneous preterm labour and the high number of low birthweight infants born
      after treating these women.

PMID- 15715609
TI  - Maintenance tocolysis.
AB  - BACKGROUND: Women who are undelivered after 48 hours of tocolysis remain at
      increased risk of preterm labour, but it is not clear whether prolonged treatment
      is effective. OBJECTIVE: To review the current evidence for the effectiveness of
      maintenance tocolysis. METHODS: The results of published systematic reviews were
      summarised. RESULTS: Four systematic reviews and two trials published too
      recently for inclusion were identified. Maintenance tocolysis with beta-agonists
      and magnesium sulphate was ineffective in prolonging gestation or reducing any
      adverse fetal outcomes. One trial of maintenance tocolysis with nifedipine was
      underpowered to rule out an effect on prolonging gestation. One trial using the
      oxytocin receptor blocker, atosiban, showed that this drug used as maintenance
      tocolysis does prolong gestation, but the trial was too small to demonstrate any
      reduction in substantive fetal outcomes. CONCLUSIONS: There is insufficient
      evidence to justify the routine use of maintenance tocolysis in preterm labour.
      It remains plausible that prolongation of gestation might be beneficial in
      selected cases of very preterm labour where fetal compromise and infection have
      been ruled out. The only tocolytic that has been shown to prolong gestation when
      used as maintenance therapy is atosiban.

PMID- 15715610
TI  - Best anesthetic method for inguinal hernia repair?

PMID- 15715611
TI  - Reduction of opioid-related adverse events using opioid-sparing analgesia with
      COX-2 inhibitors lacks documentation: a systematic review.
AB  - BACKGROUND: We have reviewed opioid-related adverse events in studies of opioid
      sparing with cyclooxygenase-2 (COX-2) inhibitors compared with placebo in
      postoperative pain. METHODS: Randomized, controlled trials were evaluated.
      Outcome measures were significant reduction in consumption of supplementary
      opioids with the COX-2 inhibitors and reported opioid-related adverse events
      (nausea, vomiting, constipation, dizziness, sedation, pruritus and/or urinary
      retention) 0-24 h after surgery. RESULTS: Nineteen studies including 26
      comparisons of four COX-2 inhibitors (rofecoxib, celecoxib, parecoxib and
      valdecoxib) were evaluated, in which significant opioid-sparing averaging about
      35% with COX-2 inhibitors and opioid-related adverse events were reported. The
      trials were in general of high quality (median Oxford quality score 4) but the
      reporting quality of adverse events was poor. Opioid-related adverse events, i.e.
      vomiting, constipation and pruritus, were only significantly reduced with COX-2
      inhibitors in four of the 26 comparisons. Quantitative analysis of combined data
      revealed a significantly reduced risk for only dizziness; the clinical relevance
      was minor as the number needed to treat (NNT) was about 33. CONCLUSION: The
      limitation of this review is the lack of quality of data of adverse events from
      the original trials. Although supplementary opioid consumption in all trials was
      significantly reduced by on average 35% with the COX-2 inhibitors, it was only
      sporadically possible to demonstrate a clinically important reduction in opioid
      related adverse events. Data did not support the common opinion that opioid
      sparing with COX-2 inhibitors provides much clinical beneficial effect with
      respect to opioid-related adverse events. Future studies have to increase the
      awareness and proper reporting of adverse events in the postoperative period.

PMID- 15715612
TI  - Anaesthetic practice for groin hernia repair--a nation-wide study in Denmark 1998
      2003.
AB  - BACKGROUND: Recent scientific data suggest that local infiltration anaesthesia
      for inguinal hernia surgery may be preferable compared to general anaesthesia and
      regional anaesthesia, since it is cheaper and with less urinary morbidity.
      Regional anaesthesia may have specific side-effects and is without documented
      advantages on morbidity in this small operation. METHODS: To describe the use of
      the three anaesthetic techniques for elective open groin hernia surgery in
      Denmark from January 1st 1998 to December 31st 2003, based on the Danish Hernia
      Database collaboration. RESULTS: In a total of 57,505 elective open operations
      63.6% were performed in general anaesthesia, 18.3% in regional anaesthesia and
      18.1% in local anaesthesia. Regional anaesthesia was utilized with an increased
      rate in elderly and hospitalized patients. Outpatient surgery was most common
      with local infiltration anaesthesia. CONCLUSION: Use/choice of anaesthesia for
      groin hernia repair is not in accordance with recent scientific data. Use of
      spinal anaesthesia should be reduced and increased use of local anaesthesia is
      recommended to enhance recovery and reduce costs.

PMID- 15715613
TI  - Intrathecal edaravone, a free radical scavenger, is effective on inflammatory
      induced pain in rats.
AB  - BACKGROUND: Free radicals have some roles in inflammation and systemic and local
      tissue injuries. (Free radical scavengers are neuroprotective against excitotoxic
      insults.) Therefore, we hypothesized that free radical scavenger would be
      analgesic on pain induced by excitotoxicity or inflammation. The purpose of this
      study was to investigate analgesic effects of intrathecally administered
      edaravone, a free radical scavenger, on thermal and inflammatory pain. METHODS:
      Sprague-Dawley rats were implanted with lumbar intrathecal catheters. Edaravone
      0.05, 0.1, 0.5, and 1 mg per 20 microl or saline 20 microl (control) were
      administered intrathecally, and the withdrawal response to thermal stimulation to
      the tail (tail-flick test) or flinch responses to subcutaneous formalin injection
      into the hind paw (formalin test) were tested. General behaviour and motor
      function were also examined. In each dose group, eight rats were used. RESULTS:
      No dose-dependent analgesic effects were observed in the tail-flick test.
      However, dose-dependent analgesia was obtained in both phase 1 and 2 of the
      formalin test. The 50% effective dose values were 0.25 mg (95% confidence
      interval, 0.11-0.56 mg) in phase 1 and 0.25 mg (95% confidence interval, 0.061
      1.05 mg) in phase 2. No behavioural side-effects nor motor dysfunction was
      observed, even with the maximum soluble dose (1 mg/20 microl). CONCLUSION:
      Intrathecally administered edaravone, a free radical scavenger, had analgesic
      effects on inflammatory-induced acute and facilitated pain but not on acute
      thermal pain, without any behavioural side-effects.

PMID- 15715614
TI  - Bolus injection of Ringer's solution and dextran 1 kDa during induction of spinal
      anesthesia.
AB  - BACKGROUND: Arterial hypotension following induction of spinal anesthesia is
      difficult to prevent with infusion fluids. In a randomized, unblinded and
      controlled study we evaluated whether a rapid fluid administration planned
      according to volume kinetic analysis is followed by a more stable blood pressure.
      METHODS: Spinal anesthesia was induced in 75 surgical patients, using one of
      three different fluid regimens: intravenous 'bolus injection' of 5 ml kg(-1) of
      Ringer's acetate over 3 min, 2 ml kg(-1) of low-molecular weight (1 kDa) dextran
      over 3 min, or a constant-rate infusion of 15 ml kg(-1) of Ringer's acetate over
      40 min (controls). The kinetics of the fluid was studied in five patients in each
      group and also in eight volunteers. RESULTS: The decrease in mean arterial
      pressure averaged 28%, 27% and 26%, respectively, and was fully developed 16 min
      after the induction. The height of the block, but not the fluid programme,
      correlated with the hypotension. Nausea or near-fainting associated with marked
      hypotension or bradycardia was recorded in none, five (20%) and two (8%) of the
      patients, respectively. Both bolus injections were followed by translocation of
      fluid from the peripheral tissues to the bloodstream, which maintained the plasma
      dilution at about 10% for at least 30 min until surgery began. CONCLUSION: A
      brisk infusion of Ringer's solution or dextran 1 kDa over 3 min was followed by
      the same decrease in arterial pressure as a longer and 3-5-times larger infusion
      of Ringer's solution over 40 min during induction of spinal anesthesia.

PMID- 15715615
TI  - Preemptive effect of intravenous ketamine in the rat: concordance between pain
      behavior and spinal fos-like immunoreactivity.
AB  - BACKGROUND: The purpose of this study was to compare behavioral antinociceptive
      responses with spinal fos-like immunoreactivity (FLI) for a intravenous ketamine
      injection between pre vs. postformalin administration in rats. METHODS: Sprague
      Dawley rats (250-300 g) were prepared to receive either saline or ketamine. All
      rats were randomly divided into three groups: control, pretreatment and post
      treatment group. Formalin (5%) 100 microl was injected into the hindpaw. Pain
      related behavior and FLI in the lumbar spinal cord was examined. RESULTS:
      Flinches of phase 2 were 239.3 (22,8), 118.6 (7,5) (P < 0.05 vs. control and post
      treatment group), and 186.7 (16,6) in the control, pre and, post-treatment
      groups, respectively. Fos-like immunoreactivity expression was significantly
      correlated with phase 2 flinching behavior (P < 0.001). CONCLUSION: Pretreatment
      with intravenous ketamine inhibits inflammatory pain behavior and FLI expression
      following a formalin injection in rats, suggesting that pretreatment of ketamine
      plays an important role in preemptive analgesia.

PMID- 15715616
TI  - Pre-anesthetic presence of an injured dam influences pups' locomotor behavior
      during emergence from anesthesia in rats.
AB  - BACKGROUND: Pre-anesthetic mother-infant interaction is an important factor for
      smooth emergence of pediatric anesthesia. In many mammalian species, disruptions
      of the mother-infant relationship cause psychological and behavioral changes.
      This study was to investigate whether or not pre-anesthetic presence of an
      injured dam has an impact on locomotor behavior of rat pups. METHODS: We used a
      video-tracking system to test the effects of pre-anesthetic relations between
      pups and their dams on pups' locomotor behavior during emergence from general
      anesthesia, in 40 3-week-old Sprague-Dawley male rats. Pups were divided into two
      groups: pups housed with a dam (n = 20) and those housed with an injured dam (n =
      20). Pups were anesthetized with 1.2% halothane for 30 min. At emergence, we
      recorded their locomotor behavior for 15 min. RESULTS: Pre-anesthetic
      manipulation to dams significantly increased the distance traveled by pups.
      However, the manipulation did not cause any difference in the maximum velocity.
      CONCLUSION: Pre-anesthetic presence of an injured dam influenced pups' locomotor
      behavior at emergence from anesthesia.

PMID- 15715617
TI  - Change in anaesthetic practice for Caesarean section in Germany.
AB  - BACKGROUND: Initial data from 1996 revealed that in contrast to several other
      countries general anaesthesia was the preferred anaesthetic technique for
      Caesarean section in Germany. However, anaesthetic practice for Caesarean section
      has changed during the last decades world-wide. This investigation was performed
      to obtain more actual data on anaesthetic procedures in obstetric patients in
      German hospitals. METHODS: Questionnaires on the practice of anaesthesia for
      Caesarean section were mailed to 918 German departments of anaesthesiology.
      Furthermore, the survey evaluated severe perioperative complications in obstetric
      patients. RESULTS: The 397 completed replies in this survey represent 41.3% of
      all German deliveries in 2002. Spinal anaesthesia is now the most common
      technique (50.5%) for elective Caesarean section. In case of urgent and emergency
      Caesarean, delivery figures decrease to 34.6% and 4.8%, respectively. Epidural
      anaesthesia is performed in 21.6% of scheduled and 13.2% and 1.0% of non
      scheduled urgent or emergency Caesarean sections, respectively. Four maternal
      deaths and several non-fatal episodes of gastric content aspiration were reported
      by the respondents. CONCLUSIONS: Compared to data obtained 6 years ago a
      significant increase in regional anaesthesia for Caesarean section has developed,
      with spinal anaesthesia being the preferred technique. Surveys can help to
      initiate discussion and improve current practice of anaesthetic care.

PMID- 15715618
TI  - The effects of ketamine and propofol on bacterial translocation in rats after
      burn injury.
AB  - BACKGROUND: Bacterial translocation (BT) occurs after thermal injury and may
      result from an ischemic intestinal insult. The aim of the study was to
      investigate the effects of ketamine and propofol as anesthetic agents on BT in an
      animal model of burn injury. METHODS: Sixty male Wistar Albino rats were randomly
      assigned to six groups of 10 rats each. Anesthesia was induced and maintained
      with ketamine in groups 1, 2 and 3 and with propofol in groups 4, 5 and 6 during
      6 h. Groups 2, 3, 5 and 6 received 30% total body surface area (TBSA) third
      degree burns. Groups 1 and 4 had no burn injury. Then, they were allowed to
      recover from the anesthesia at the end of 6 h. Mean arterial pressure (MAP) was
      monitored continuously and maintained within 10% of baseline (before burn injury)
      levels in all animals. Animals in groups 3 and 6 had a laparotomy to obtain a
      tissue sample from the terminal ileum for determination of intestinal lipid
      peroxidation by-product malondialdehyde (MDA) before (baseline) and 6 and 24 h
      after burn injury (ABI). So these animals were not included in the BT studies. At
      postburn 24 h, animals in groups 1, 2 and 4, 5 were sacrified and samples were
      taken from the mesenteric lymph nodes (MLN), liver and spleen for bacteriologic
      cultures. RESULTS: The incidence of BT was found to be significantly higher in
      group 2 than in all the other groups. Bacterial translocation incidence of group
      5 was not significantly different from that of groups 4 and 1. Group 5 was
      associated with a significantly reduced number of enteric organisms per gram of
      tissue compared to group 2. Baseline MDA contents of groups 3 and 6 were similar.
      Ileal MDA levels were increased in group 3, but there were no significant changes
      in group 6 at 6 and 24 h ABI compared to baseline. CONCLUSION: Our results
      suggest that propofol as an anesthetic agent may prevent BT by scavenging
      reactive oxygen species and inhibiting lipid peroxidation in an animal model of
      burn injury.

PMID- 15715619
TI  - Inhaled and intravenous corticosteroids both attenuate chlorine gas-induced lung
      injury in pigs.
AB  - BACKGROUND: The accidental release of chlorine gas is a constant threat in urban
      areas. The purpose of this randomized, blinded, controlled experiment was to
      examine the effects of post-injury administration of inhaled or intravenous
      corticosteroid in chlorine gas-injured pigs followed for 23 h. METHODS:
      Anaesthetized, ventilated pigs (n = 24) in the prone position were exposed to
      chlorine gas (400 parts per million in air) (1160 mg/m3) for 15 min, then
      randomly allocated to receive inhaled budesonide (BUD) and intravenous placebo,
      intravenous betamethasone (BETA) and inhaled placebo or inhaled and intravenous
      placebo. Haemodynamics, gas exchange and lung mechanics were evaluated for 23 h
      after exposure to chlorine gas. RESULTS: Airway and pulmonary artery pressures
      increased and arterial oxygenation fell sharply (from 13.5 +/- 0.8 to 6.7 +/- 0.9
      kPa, P < 0.001) after chlorine gas exposure. These immediate changes were
      followed by a gradual improvement over 5-7 h to a stable level of dysfunction for
      the rest of the experiment in placebo animals. Arterial oxygen tension, pulmonary
      vascular resistance and airway pressure recovered faster and more completely in
      the budesonide and betamethasone groups than in the placebo group (P < 0.01).
      Lung wet weight to dry weight ratios were greater in the placebo group than in
      the budesonide and betamethasone groups (6.34 +/- 0.59 vs. 5.56 +/- 0.38 and 5.53
      +/- 0.54, respectively, P < 0.05). There was a trend towards lower histological
      injury scores compared with placebo in animals that received budesonide (P =
      0.05) or betamethasone (P = 0.07). CONCLUSION: Treatment of chlorine gas lung
      injury with nebulized budesonide or intravenous betamethasone had similar
      positive effects on recovery of lung function.

PMID- 15715620
TI  - Plasma concentration of procalcitonin and systemic inflammatory response syndrome
      after colorectal surgery.
AB  - BACKGROUND: To study whether plasma concentrations of procalcitonin (PCT),
      interleukin-6 (IL-6), complement 3a (C3a), C-reactive protein and white blood
      cell count (WBC) correlate with the presence of systemic inflammatory response
      syndrome (SIRS) during the early post-operative period after major colorectal
      surgery. METHODS: Prospective, observational study during the first 24 h post
      operatively. The setting for the study was the operating theatre and the recovery
      unit at the university hospital. Fifty consecutive patients, operated on
      electively with major resection of the large bowel or rectum. PCT levels
      increased significantly to the maximum level 18 h postoperatively. PCT levels
      were significantly higher in the SIRS group in comparison to the non-SIRS group
      of patients 6 and 12 h after surgery (P < 0.05). The IL-6 levels were increased
      directly after the surgery and then decreased gradually in both study groups.
      Twenty-four hours after the surgery, C3a levels decreased and then returned to
      normal levels. Twenty-four hours post-operatively, patients with SIRS had a
      higher plasma concentration of C3a compared with patients without SIRS (P <
      0.05). CRP and WBC increased during the study period in both groups (P < 0.05).
      CONCLUSIONS: During the early post-operative period after uncomplicated major
      abdominal surgery, SIRS was reflected by the increase in plasma PCT and C3a
      concentrations. IL-6, CRP and WBC increased to the same extend in both the SIRS
      and the non-SIRS group of patients.

PMID- 15715621
TI  - Bi-level positive airway pressure ventilation reduces the oxygen cost of
      breathing in long-standing post-polio patients on invasive home mechanical
      ventilation.
AB  - BACKGROUND: Today, patients with chronic respiratory failure are commonly treated
      with non-invasive bi-level positive airway pressure ventilation, supporting
      spontaneous breathing. However, in conformity with previous clinical routine,
      many post-polio patients with chronic respiratory failure are still treated with
      invasive (i.e. via a tracheostomy) controlled mechanical ventilation (CMV). The
      aim of the study was to investigate the effect of invasive bi-level positive
      airway pressure ventilation on the work of breathing compared with that during
      the patients' ordinary CMV and spontaneous breathing without mechanical support.
      METHODS: Nine post-polio patients on invasive (tracheostomy) nocturnal CMV were
      investigated. Work of breathing was analysed by assessing differences in oxygen
      consumption (VO2) using indirect calorimetry. Hereby, the oxygen cost of
      breathing during the various ventilatory modes could be estimated and related to
      one another. Data on energy expenditure were also obtained. RESULTS: The oxygen
      cost of breathing decreased by approximately 15% during bi-level positive airway
      pressure ventilation compared with CMV and spontaneous breathing. There was no
      difference between predicted (Harris-Benedict equation) and measured energy
      expenditure. CONCLUSION: Invasive bi-level positive airway pressure ventilation
      reduces the oxygen cost of breathing in long-standing tracheostomized post-polio
      patients, compared with CMV. Furthermore, the Harris-Benedict equation provides a
      reasonable prediction of energy expenditure in this group of patients.

PMID- 15715622
TI  - Antithrombin III pretreatment reduces neutrophil recruitment into the lung in a
      rat model of abdominal sepsis.
AB  - BACKGROUND: Antithrombin III (AT III) is a serine protease inhibitor and the
      mechanism of its anti-inflammatory action is still not understood. In the present
      study, we aimed to investigate the anti-inflammatory action of AT III on lung
      injury in a rat model of sepsis. METHODS: Three groups of animals were used in
      this controlled study: the sham-operated group (sham, n = 3) which only underwent
      a laparotomy; the control group (control, n = 7) which underwent cecal ligation
      and perforation (CLP); and the AT III-treated group (AT III, n = 6) which
      underwent CLP and received intravenous (i.v.) 250 U/kg AT III 30 min before
      induction of sepsis. Rats were killed 24 h after induction of sepsis by needle
      aspiration of the right ventricle after a sternotomy, and the lungs and trachea
      were removed en bloc under ether anesthesia. RESULTS: Pulmonary accumulation of
      polymorphonuclear leukocytes (PMN) was assessed by measuring lung tissue
      myeloperoxidase (MPO) activity. Lipid peroxidation in lung tissue was assessed by
      tissue thiobarbituric acid reactive substance (TBARS) levels. The plasma
      prostacyclin level was assessed by the plasma 6-keto prostaglandin F(1alpha)(6
      keto-PGF(1alpha)) level, which is a stable derivative of prostacyclin.
      Histopathological changes in lung tissue were assessed by PMN count in the
      capillaries and alveolar spaces. The lung tissue TBARS level, MPO activity and
      PMN count in the control group were significantly higher than in the AT III group
      (P < 0.05). The change in plasma 6-keto-PGF(1alpha) level in the AT III group was
      insignificant compared with the control group (P = 0.15). CONCLUSIONS: AT III
      prevented pulmonary infiltration of PMN and subsequent injury by the endothelial
      release of prostacyclin in CLP-induced sepsis.

PMID- 15715623
TI  - High-frequency oscillatory ventilation in adults with traumatic brain injury and
      acute respiratory distress syndrome.
AB  - BACKGROUND: This study observed adverse events of rescue treatment with high
      frequency oscillatory ventilation (HFOV) in head-injured patients with acute
      respiratory distress syndrome (ARDS). METHODS: Data of five male patients with
      ARDS and traumatic brain injury, median age 28 years, who failed to respond to
      conventional pressure-controlled ventilation (PCV) were analyzed retrospectively
      during HFOV. Adjusted mean airway pressure at initiation of HFOV was set to 5 cm
      H2O above the last measured mean airway pressure during PCV. Frequency of
      pulmonary air leak, mucus obstruction, tracheal injury, and need of HFOV
      termination due to increased intracranial pressure, decreased cerebral perfusion
      pressure, or deterioration in P(a)CO2 were analyzed. RESULTS: During HFOV we
      found no complications. We recorded 390 datasets of intracranial pressure,
      cerebral perfusion pressure and P(a)CO2 simultaneously. Intracranial pressure
      increased (>25 mmHg) in 11 of 390 datasets, cerebral perfusion pressure was
      reduced (<70 mmHg) in 66 of 390 datasets, and P(a)CO2 variations (<4.7 kPa; >6.0
      kPa) were observed in eight of 390 datasets after initiation of HFOV. All these
      alterations were responsive to treatment. P(a)O2/F(I)O2-ratio improved in four
      patients during HFOV. CONCLUSION: High-frequency oscillatory ventilation appears
      to be a promising alternative rescue treatment in head-injured patients with ARDS
      if continuous monitoring of intracranial pressure, cerebral perfusion pressure
      and P(a)CO2 are provided, in particular during initiation of HFOV.

PMID- 15715624
TI  - Requirements of propofol at different end-points without adjuvant and during two
      different steady infusions of remifentanil.
AB  - BACKGROUND: Some reports show no interaction between propofol and opioids,
      whereas others state such interactions. We evaluated the influence of
      remifentanil on propofol requirements at certain anesthesia end-points. METHODS:
      Elective surgical patients were randomly assigned to three groups of 15 patients
      each. Premedication was with oral diazepam 0.1 mg kg(-1). Patients were blindly
      given equal volumes of saline or remifentanil (7.5 or 30 microg kg(-1). h(-1)) 1
      min before induction of anesthesia with infusion of propofol, 30 mg kg(-1). h(
      1). We recorded times to, propofol requirements, and bispectral index at loss of
      counting (LC), loss of verbal command (LVC), loss of reaction to tetanic
      stimulation (LRT), and onset of burst suppression pattern (BSP) of
      electroencephalography. RESULTS: In the remifentanil groups end-points were
      attained significantly faster and with lower doses of propofol than in the saline
      group. BIS-values were significantly different at LRT and BSP end-points.
      CONCLUSIONS: We conclude that remifentanil infusion started before induction of
      propofol anesthesia significantly reduces propofol requirements at all end
      points. The results suggest that remifentanil accelerates the hypnotic onset of
      propofol.

PMID- 15715625
TI  - Effects of coagulation factor deficiency on plasma coagulation kinetics
      determined via thrombelastography: critical roles of fibrinogen and factors II,
      VII, X and XII.
AB  - BACKGROUND: Thrombelastography (TEG) is used to assess coagulopathy. However, a
      comprehensive characterization of the effects of specific coagulation factor
      deficiencies and mode of activation on TEG data does not exist. METHODS:
      Thrombelastography was performed for 15 min with control plasma and plasmas
      deficient (<1% activity) in Factors II, V, VII, VIII, IX, X, XI, XII, or XIII
      activated with celite (0.28 mg ml(-1)) or tissue factor (TF, 0.1%) (n = 6 per
      condition). Additional fibrinogen concentration activity (75-345 mg dl(-1)) and
      Factor II, VII, X and XII activity-response relationships (1%, 6.25%, 12.5%, 25%,
      50% and 100% activity) were obtained (n = 8 per condition). Thrombelastography
      parameters included reaction time (R), angle (alpha), and clot strength (A,
      amplitude; G, elastic modulus). RESULTS: Celite activation of FXII-deficient
      plasma, TF activation of FVII-deficient and FX-deficient plasma, and celite or TF
      activation of FII-deficient plasma resulted in an almost undetectable clot.
      Compared to control values, celite activation of plasmas deficient in FXI, FIX
      and FVIII resulted in prolonged R and decreased alpha values, whereas TF
      activation resulted in decreased alpha values. Celite and TF activation of FV
      deficient plasma resulted in prolonged R and decreased alpha values, whereas
      FXIII-deficient plasma had decreased alpha, A and G-values compared to control
      values. CONCLUSIONS: The fundamental finding of this study is that coagulation
      factor deficiencies affect TEG parameters in both a factor-dependent and
      activation-dependent fashion. Utilizing both celite and TF activation improves
      the diagnostic power of TEG. Based on such TEG data, more targeted administration
      of blood products could potentially help improve perioperative hemostatic
      outcomes.

PMID- 15715626
TI  - Fit and seal characteristics of a new paediatric tracheal tube with high volume
      low pressure polyurethane cuff.
AB  - BACKGROUND: To evaluate a new paediatric tracheal tube (Microcuff, Weinheim,
      Germany) with an ultrathin high volume-low pressure polyurethane cuff. METHODS:
      With approval of the Hospital Ethics Committee tracheas of children undergoing
      general anaesthesia were intubated using a Microcuff tube. Tube sizes were
      selected according to: internal diameter (mm) = age/4 + 3.5 in children aged > or
      = 2 years. In newborns (> or = 3 kg) < or = 1 year, ID 3.0-mm tubes, and in
      children from 1 to 2 years, internal diameter 3.5-mm tubes were used. Tubes were
      classified too large if no air leakage was obtained at an airway pressure of 20
      cm H2O with the cuff not inflated. Sealing pressure was assessed by auscultation.
      Post-extubation croup requiring therapy was noted. RESULTS: Five-hundred children
      were studied. In eight children the tubes were too large. Sealing pressure was
      9.7 +/- 2.5 cm H2O (4-20). In two patients postextubation croup required singular
      short-term therapy. CONCLUSIONS: Microcuff paediatric tracheal tubes provided
      tracheal sealing with cuff pressures considerably lower than usually accepted.
      The rate of tube exchange was very low (1.6%), as was the rate of airway
      morbidity (croup requiring therapy; 0.4%).

PMID- 15715627
TI  - Multimodal approach to rapid discharge after endoscopic thoracic sympathectomy.
AB  - BACKGROUND: After a large experience (more than 10 years) with bilateral
      endoscopic thoracic sympathectomy (ETS) surgery on an outpatient basis, we
      studied prospectively a multimodal approach to rapid discharge patients
      undergoing this procedure. METHODS: One hundred and seventeen consecutive
      patients, aged 13-60 years, ASA physical status I or II, undergoing outpatient
      ETS under general anaesthesia were enrolled in this study. All patients were
      managed using a predefined multimodal clinical care protocol consisting of a
      general balanced anaesthesia. Basic demographic information was collected from
      each patient. Duration of surgery and anaesthesia and times to PACU and home
      discharge were recorded as well as intraoperative and postoperative complications
      like nausea and vomiting. RESULTS: Surgery took 41.4 +/- 22.1 min and anaesthesia
      lasted 63 +/- 21.5 min. Time between induction of anaesthesia and beginning of
      surgery and end of surgery to extubation was 15.0 +/- 2.0 and 7.2 +/- 3.1 min,
      respectively. It took 4.9 +/- 1.5 min from extubation to OR discharge. Time from
      PACU arrival to discharge was 12.8 +/- 6.3 min. Time of hospital stay was 132 +/-
      18 min. No patient experienced vomiting and two had nausea, representing an
      incidence of 1.7%. The only anaesthetic cause for hospital admission was a severe
      allergic reaction. CONCLUSION: Multimodal management to rapid discharge after ETS
      surgery did result in a short time to patient discharge. We confirm that
      endoscopic thoracic sympathectomy can be performed safely on an outpatient basis
      with brief postoperative hospital care and a low rate of complications.

PMID- 15715628
TI  - Comparison of recovery properties of desflurane and sevoflurane according to
      gender differences.
AB  - BACKGROUND: The aim of this study was to investigate the recovery properties of
      desflurane and sevoflurane in patients undergoing elective surgery, according to
      the gender differences. METHODS: In the study, 160 ASA class I-II patients aged
      between 20 and 60 years were included. The patients were assigned into two groups
      according to their gender, and these groups were randomly divided into two groups
      according to a selected volatile anaesthetic agent. Intraoperative bispectral
      index, time of postoperative achievement for end-tidal concentrations of volatile
      agents to decline 50% (ET-AA%50), time for extubation, time for eye opening and
      orientation, and time for bispectral index values to reach control values were
      recorded. Aldrete scores and error points of a delayed memory recall test were
      determined. RESULTS: Desflurane groups had a shorter ET-AA%50 time, extubation
      and eye-opening time in male and female patients compared to the sevoflurane
      groups, and these results were statistically significant (P < 0.05). In both the
      desflurane and sevoflurane groups, ET-AA%50 time, extubation and eye-opening time
      were shorter in male patients than in female patients, and these results were
      also statistically significant (P < 0.05). There were no significant differences
      among the groups in terms of Aldrete scores and error points of delayed memory
      recall test (P > 0.05). CONCLUSION: In conclusion, early recovery time was
      shorter in male patients compared to female patients in both the desflurane and
      sevoflurane groups. Additionally, in the desflurane groups it was shorter in the
      sevoflurane groups for both genders.

PMID- 15715629
TI  - Less local pain on intravenous infusion of a new propofol emulsion.
AB  - BACKGROUND: Local pain at the site of intravenous (iv) injection of propofol
      remains a considerable problem in clinical anaesthesiology, and particularly so
      in infants. The aim of the present study was to compare the influence of two
      different emulsions of propofol on local pain following iv administration.
      METHODS: Eighty adult patients (ASA I-II) scheduled for ear-nose-throat or
      plastic surgery were randomly allocated into two study groups: A and B. A 1.0-mm
      teflon cannula (BD, Helsingborg, Sweden) was inserted into a dorsal vein on each
      hand. Each patient was given two 3.0-ml iv bolus injections of two different
      propofol emulsions of 10 mg ml(-1) over 2 s, one in each cannula, at 5-min
      intervals. The first study drug administered was Diprivan (AstraZeneca,
      Sodertalie, Sweden) in group A (n = 34) and Propofol-Lipuro (Braun, Melsungen,
      Germany) in group B (n = 39). Each patient was then asked by a blinded
      investigator to score maximal pain intensity on a visual analogue scale (VAS).
      RESULTS: The maximal intensity of propofol-induced local pain was significantly
      (P < 0.0001) lower after Propofol-Lipuro than after Diprivan--median 1 (25th
      percentile: 0; 75th percentile: 2) range 0-6 vs. 3 (0; 5) 0-9 VAS units.
      CONCLUSION: The considerably lower intensity of local pain found to be associated
      with iv administration of the new drug formula Propofol-Lipuro indicates that
      emulsions of propofol based on medium- and long-chain triglycerides have a
      clinical advantage over traditional ones for induction of anaesthesia.

PMID- 15715630
TI  - Tube tip in pharynx (TTIP) ventilation: simple establishment of ventilation in
      case of failed mask ventilation.
AB  - BACKGROUND: Mask ventilation occasionally fails. Alternative readily available
      and simple methods to establish ventilation in these cases are needed. METHODS:
      Retrospective description of cases in which a new technique, tube tip in pharynx
      (TTIP) ventilation, was employed for restoring ventilation in case of failed
      facemask ventilation during induction of anaesthesia. The technique involves a
      standard endotracheal tube and can be performed single-handed: A standard
      endotracheal tube was placed via the mouth with the tip in the pharynx and the
      cuff was inflated. By placing the fourth and fifth fingers below the ramus of the
      mandible, the third finger below the lower lip, the second finger above the upper
      lip and on one side of the nose and the first finger on the other side of the
      nose, an open airway is restored. Chin lift is inherent in the grip, thus
      contributing to opening of the airway. RESULTS: In all four cases of failed mask
      ventilation the anaesthetist could establish an open airway and subsequent
      ventilation without the need for an assistant. There were no indications of
      gastric insufflation. CONCLUSION: The TTIP technique established ventilation in
      all four patients after abandoned facemask ventilation. The technique only
      involves one person and an endotracheal tube and warrants to be included in the
      armamentarium of anaesthetists. Further prospective studies are needed to refine
      the technique and delimit its indications.

PMID- 15715631
TI  - Computed tomography--a possible aid in the diagnosis of smoke inhalation injury?
AB  - Inhalation injury is an important contributor to morbidity and mortality in burn
      victims and can trigger acute lung injury and acute respiratory distress syndrome
      (ARDS) (1-3). Early diagnosis and treatment of inhalation injury are important,
      but a major problem in planning treatment and evaluating the prognosis has been
      the lack of consensus about diagnostic criteria (4). Chest radiographs on
      admission are often non-specific (5, 6), but indicators include indoor fires,
      facial burns, bronchoscopic findings of soot in the airways, and detection of
      carbon monoxide or cyanide in the blood (7). Changes in the lungs may be detected
      by bronchoscopy with biopsy, xenon imaging, or measurement of pulmonary
      extracellular fluid (4, 5, 8). These methods have, however, been associated with
      low sensitivity and specificity, as exemplified by the 50% predictive value in
      the study of Masanes et al. (8). Computed tomographs (CTs) are better than normal
      chest radiographs in the detection of other pulmonary lesions such as pulmonary
      contusion (9, 10). The importance of CT scans in patients with ARDS has been
      reviewed recently (9), but unfortunately there has been no experience of CT in
      patients with smoke inhalation injury. To our knowledge, there are only two
      animal studies reporting that smoke inhalation injury can be detected by CT (4,
      11); specific changes in human CT scans have not yet been described. Therefore,
      confronted with a patient with severe respiratory failure after a burn who from
      the history and physical examination showed the classic risk factors for
      inhalation injury, we decided to request a CT.

PMID- 15715632
TI  - Continuous lateral popliteal block with stimulating catheters.
AB  - Foot surgery often induces severe postoperative pain. Sciatic nerve block is a
      good alternative for its treatment. We report two cases of continuous lateral
      popliteal sciatic nerve block using two different stimulating catheters. The
      lateral approach may offer some advantages. Stimulating catheters may be useful
      to verify correct catheter tip positioning. This technique seem to be easy to use
      and provided excellent pain relief.

PMID- 15715633
TI  - An unusual cause of difficult intubation in a patient with a large cervical
      anterior osteophyte: a case report.
AB  - This report describes a case in which a large anterior osteophyte on the C2 and
      C3 vertebrae, due to ankylosing spondylitis, resulted in distortion of the
      anatomy of the upper airway and difficult intubation. Ankylosing spondylitis (AS)
      is a progressive inflammatory disease, characterized by stiffening of the joints
      and ligaments. Stiffness of the cervical spine, atlanto-occipital,
      temporomandibular and cricoarytenoid joints may cause difficult intubation (1).
      This report describes a case in which a large anterior osteophyte on the C2 and
      C3 vertebrae, associated with AS, resulted in distortion of the anatomy of the
      upper airway and difficult intubation.

PMID- 15715634
TI  - Securing epidural catheter.

PMID- 15715635
TI  - Cardiac arrest during desflurane anaesthesia in a patient with Duchenne's
      muscular dystrophy.

PMID- 15715636
TI  - Life-style changes in US Academic medicine: learning from the Europeans.

PMID- 15715638
TI  - Desulphurization of dibenzothiophene and diesel oils by bacteria.
AB  - AIMS: To study the desulphurization of dibenzothiophene (DBT), a recalcitrant
      thiophenic component of fossil fuels, by two bacteria namely Rhodococcus sp. and
      Arthrobacter sulfureus isolated from oil-contaminated soil/sludge in order to use
      them for reducing the sulphur content of diesel oil in compliance with
      environmental regulations. METHODS AND RESULTS: The desulphurization pathway of
      DBT by the two bacteria was determined by gas chromatography (GC) and GC-mass
      spectrometry. Both organisms were found to produce 2-hydroxy biphenyl (2-HBP),
      the desulphurized product of DBT. Sulphur contents of culture supernatants of
      Rhodococcus sp. and A. sulfureus grown with DBT as sole sulphur source were
      analysed by X-ray fluorescence indicating sulphur levels of 8 and 10 ppm,
      respectively, as compared with 27 ppm in control. In order to study
      desulphurization of diesel oils obtained from an oil refinery, resting cell
      studies were carried out which showed a decrease of about 50% in sulphur content
      of the oil obtained from the hydrodesulphurization (HDS) unit of the refinery.
      CONCLUSIONS: Rhodococcus sp. and A. sulfureus selectively remove sulphur from DBT
      to form 2-HBP. Application of these bacteria for desulphurization of diesel
      showed promising potential for decreasing the sulphur content of diesel oil.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The process of microbial desulphurization
      described herein can be used for significantly reducing the sulphur content of
      oil, particularly, after the process of HDS which would help in meeting the
      regulatory standards for sulphur level in diesel oil.

PMID- 15715639
TI  - Real-time PCR for the detection of Escherichia coli O157:H7 in dairy and cattle
      wastewater.
AB  - AIMS: Developing and evaluating a rapid real-time polymerase chain reaction (PCR)
      method for the identification of Escherichia coli O157:H7 in cattle and dairy
      wastewater samples produced from mozzarella cheese factories, without pre
      enrichment step before DNA extraction. METHODS AND RESULTS: Wastewater samples
      were collected from a dairy farm producing mozzarella cheese and located in
      Puglia (south of Italy). Plate count and other microbial assays were performed 1
      h after sampling. Wastewater samples were artificially inoculated with 10(4),
      10(7) and 10(8) cells ml(-1) of E. coli O157:H7, strain EDL933. PCR protocols for
      stx1, stx2 and eae genes were first tested on pure DNA extracted from type
      strains, in order to optimize the amplification conditions and reagent
      concentration before real-time PCR experiments. Three specific fragments of ca
      106, 150 and 200 bp corresponding to genes eae, stx1 and stx2, respectively, were
      obtained. Real-time PCR experiments were performed with DNA extracted from dairy
      and manure wastewater samples inoculated with 10(4), 10(7) and 10(8) colony
      forming units (CFU) ml(-1) of E. coli O157:H7 strain EDL 933. The sensitivity
      limit of the assay was 10(-1) pg microl(-1) for eae, stx2 and 16SrRNA, and 1 pg
      microl(-1) for stx1 gene respectively. CONCLUSIONS: A real-time PCR protocol has
      been developed and used in order to identify potential pathogens in dairy
      wastewater, in which previous methods (including standard PCR) failed to work.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Cattle and dairy wastewater samples
      produced from mozzarella cheese factories may harbour verocytotoxin-producing E.
      coli. The availability of rapid and sensitive molecular methods may be useful to
      monitor the persistence of verocytotoxin-producing E. coli in general and to
      assess the effectiveness of wastewater treatments.

PMID- 15715640
TI  - Identification of medicinal off-flavours generated by Alicyclobacillus species in
      orange juice using GC-olfactometry and GC-MS.
AB  - AIMS: The objective of this study was to identify compounds responsible for
      medicinal off-flavours produced by different species and strains of
      Alicyclobacillus in orange juice using a combination of chromatographic-coupled
      olfactometric techniques and gas chromatography-mass spectrometry (GC-MS).
      METHODS AND RESULTS: Each of five Alicyclobacillus strains was inoculated into
      separate juice samples and incubated up to 28 days at 45 degrees C. Aroma
      compounds in the juice were analysed by GC-olfactometry (GC-O) and confirmed
      using GC-MS. GC-O identified three components that were described as
      medicinal/antiseptic. Microbial populations were enumerated at timed intervals by
      spiral plating onto Alicyclobacillus agar. Within 28 days incubation, all five
      strains produced medicinal off-aromas from guaiacol and at least one halogenated
      phenol. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to evaluate
      individual juice aroma components produced by Alicyclobacillus species using
      olfactometry and to demonstrate that at least three medicinal off-flavour
      compounds are associated with the growth of alicyclobacilli in orange juice.

PMID- 15715641
TI  - Novel method for cell immobilization and its application for production of
      organic acid.
AB  - AIMS: The aim was to develop a novel and simple technique for the entrapment of
      fungal hyphae. METHODS AND RESULTS: A novel immobilization technique was
      developed by using a structural fibrous network (SFN) of papaya wood as an
      immobilizing matrix. The technique is simple and a stable entrapment was achieved
      simply by inoculating the Aspergillus terreus hyphae within culture medium
      containing SFN pieces for 3 days, without any prior chemical treatment. Results
      show that SFN has no detrimental effect both on growth and bioactivity of fungi.
      A 23.5% increase in the itaconic acid production by SFN-immobilized A. terreus
      was noted when compared with free biomass. SFN-immobilized fungal biomass
      retained 95% itaconic acid productivity for five repeated batch cycles, 7 days
      each, without any disintegration/release of hyphae in the production medium.
      CONCLUSIONS: This is the first report on the use of SFN, a structural material,
      as an immobilizing matrix for the entrapment of any kind of microbial biomass and
      its application in organic acid. SIGNIFICANCE AND IMPACT OF THE STUDY: The low
      cost of SFN and simplicity of the technique applied for immobilization of fungal
      hyphae within/onto SFN make its use ideal for the immobilization of fungal
      biomass to produce commercially valuable products.

PMID- 15715642
TI  - The cytotoxic properties of a plant lipid transfer protein involve membrane
      permeabilization of target cells.
AB  - AIMS: To determine whether Ha-AP10, a member of the plant lipid transfer proteins
      (LTPs) family produces a direct cytotoxic effect on fungal cells mediated by
      membrane permeabilization. LTPs can inhibit fungal growth and are considered
      members of the ubiquitous class of antimicrobial peptides. However, the way they
      exert their effects on target cells is not yet understood. METHODS AND RESULTS:
      Viability assays demonstrate that Ha-AP10 acts as a fungicidal compound but no
      harmful effect is observed on plant cells. Liposome leakage assays show that the
      protein induces a moderate release of fluorescent probes encapsulated in model
      membranes, indicating its ability to interact with phospholipids. Using a
      fluorescent indicator of damage at the membrane level, we demonstrate that Ha
      AP10 is able to induce the permeabilization of intact fungal spores in a dose
      dependent manner. CONCLUSION: The results presented here demonstrate the
      permeabilization of fungal spores caused by Ha-AP10. SIGNIFICANCE AND IMPACT OF
      THE STUDY: To our knowledge, this is the first demonstration of fungal membrane
      damage by an LTP, giving a clue to elucidate the basis of its antimicrobial
      properties.

PMID- 15715643
TI  - Harvesting of Spirulina platensis by cellular flotation and growth stage
      determination.
AB  - AIM: To investigate an effective harvesting method for Spirulina platensis.
      METHODS AND RESULTS: Eighty per cent of S. platensis cells in the logarithmic
      growth phase were harvested by flotation when the cells were set in a static
      condition for 2 h. The optimum harvesting time was about day 6 of cultivation.
      The flotation activity of S. platensis cells was enhanced by the addition of
      NaCl. CONCLUSIONS: The harvesting of S. platensis by flotation is a cost
      effective and straightforward method that can retain the algal quality. The
      optimum harvesting time of S. platensis can be predicted by the cellular protein
      to carbon ratio. SIGNIFICANCE AND IMPACT OF THE STUDY: Flotation harvesting is
      also applicable to other cyanobacteria with gas vesicles.

PMID- 15715644
TI  - Isolation and identification of lactic acid bacteria from soil using an
      enrichment procedure.
AB  - AIMS: To survey, and identify and classify the ecological distribution of lactic
      acid bacteria from soil in Japan and Taiwan. METHODS AND RESULTS: Acid-producing
      bacteria were isolated from 68 soil samples, collected from Japan and Taiwan, in
      the rhizospheres of fruit trees, from the floor of a henhouse and around a horse
      farm. All isolates were identified by physiological and genetic tests. Thirty-two
      of the 54 isolates were identified as lactic acid bacteria (LAB), 16 as spore
      forming lactic acid bacteria, five as Clostridium and one as Bacillus. These
      lactic acid bacteria represent five genera: Lactobacillus, Lactococcus,
      Enterococcus, Leuconostoc and Weissella. CONCLUSIONS: A high rate of isolating
      lactic acid bacteria was obtained from soil. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study suggests that soil may be a common source for the isolation of
      lactic acid bacteria.

PMID- 15715645
TI  - Inactivation of polyketide synthase and related genes results in the loss of
      complex lipids in Mycobacterium tuberculosis H37Rv.
AB  - AIMS: Phthiocerol dimycocerosate (PDIM) waxes and other lipids are necessary for
      successful Mycobacterium tuberculosis infection, although the exact role of PDIM
      in host-pathogen interactions remains unclear. In this study, we investigated the
      contribution of tesA, drrB, pks6 and pks11 genes in complex lipid biosynthesis in
      M. tuberculosis. METHODS AND RESULTS: Four mutants were selected from M.
      tuberculosis H37Rv transposon mutant library. The transposon insertion sites were
      confirmed to be within the M. tuberculosis open reading frames for tesA (a
      probable thioesterase), drrB (predicted ABC transporter), pks11 (putative
      chalcone synthase) and pks6 (polyketide synthase). The first three of these
      transposon mutants were unable to generate PDIM and the fourth lacked novel polar
      lipids. CONCLUSIONS: Mycobacterium tuberculosis can be cultivated in vitro
      without the involvement of certain lipid synthesis genes, which may be necessary
      for in vivo pathogenicity. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of
      transposon mutants is a new functional genomic approach for the eventual
      definition of the mycobacterial 'lipidome'.

PMID- 15715646
TI  - Quantification of Microthrix parvicella in activated sludge bacterial communities
      by real-time PCR.
AB  - AIMS: This study was to develop a simple and reliable method for quantifying
      Microthrix parvicella 16S rRNA gene copies and its application to activated
      sludge samples collected from wastewater treatment plants (WWTP) with and without
      foaming problems. METHODS AND RESULTS: The relative frequency of M. parvicella
      was determined by combining real-time PCR assays for quantification of total
      bacterial 16S rRNA gene copies and M. parvicella 16S rRNA gene copies. The
      developed method was applied to analyse 32 activated sludge samples obtained from
      German WWTP. The level of M. parvicella 16S rRNA gene copies in the 18 nonfoaming
      samples was below 3% of the total number of 16S rRNA gene copies and in the range
      of 0-18% for the 14 foaming samples. CONCLUSIONS: The described method allows
      reliable monitoring of the amount of M. parvicella in activated sludge samples.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The described method may become an
      important component of a warning system for forthcoming bulking and foaming
      episodes.

PMID- 15715647
TI  - Acetophenones with selective antimycobacterial activity.
AB  - AIMS: Mycobacteria are a serious cause of infections in humans, with limited
      treatment options, as no new antibiotics have been developed against mycobacteria
      since the 1960s. In this study, the antimycobacterial activity of a small library
      of acetophenone (AP) compounds was analysed. METHODS AND RESULTS: Twenty-three AP
      derivatives were examined for activity against mycobacteria using a microbroth
      assay. The compounds were bacteriostatic, with the most effective
      (cyclohexylacetophenone and piperidinoacetophenone) having minimal inhibitory
      concentrations of 246 microM. Active compounds tended to be more hydrophobic, and
      may work by alkylation of as yet undetermined intracellular target protein(s).
      Cytotoxicity against eukaryotic cells was also determined and appears to be
      unrelated to the bacteriostatic activity. SIGNIFICANCE AND IMPACT OF THE STUDY:
      AP may serve as a novel group of useful therapeutics against the mycobacteria.

PMID- 15715648
TI  - Isolation of lipid- and polysaccharide-degrading micro-organisms from subtropical
      forest soil, and analysis of lipolytic strain Bacillus sp. CR-179.
AB  - AIMS: To isolate the micro-organisms from three soil samples obtained from a
      subtropical forest of Puerto Iguazu (Argentina), to analyse them for detection of
      the biotechnologically interesting enzymatic activities lipase, esterase,
      cellulase, xylanase and pectinase, and to identify the most active strain.
      METHODS AND RESULTS: A total of 724 strains were isolated using different culture
      media and temperatures, and 449 of them showed at least one of the hydrolytic
      activities pursued. Lipolytic activity of the lipid-degrading strains was further
      determined using MUF-butyrate and MUF-oleate as substrates. The alkalophilic
      strain CR-179, one of the most active for all the enzymatic activities assayed,
      was characterized and preliminarily identified by morphological, physiological
      and 16S rDNA tests, as a Bacillus sp. closely related to Bacillus subtilis.
      CONCLUSIONS: Highly hydrolytic strains were isolated from all soil samples,
      suggesting the existence of a microbial community well-adapted to nutrient
      recycling. Strain CR-179, one of the most active, has been preliminarily
      identified as a Bacillus sp. SIGNIFICANCE AND IMPACT OF THE STUDY: A collection
      of hydrolytic strains with high biotechnological potential was obtained. Presence
      of sequences codifying for a lipolytic system related to the B. subtilis group
      lipases was revealed by PCR for the best lipolytic strain.

PMID- 15715649
TI  - Molecular cloning of levan fructotransferase gene from Arthrobacter ureafaciens
      K2032 and its expression in Escherichia coli for the production of difructose
      dianhydride IV.
AB  - AIMS: To clone and overexpress a novel levan fructotransferase gene lftA from
      Arthrobacter ureafaciens K2032. METHODS AND RESULTS: The lftA gene, encoding a
      levan fructotransferase (LFTase) of 521 amino acids (aa) residues, was cloned
      from the genomic DNA of A. ureafaciens K2032, and overexpressed in Escherichia
      coli. The recombinant LFTase overexpressed in E. coli was then used to produce a
      difructose dianhydride (DFA IV) from levan. DFA IV crystals with 97% purity could
      be obtained from the reaction mixture in 83.7% yield by using a natural
      crystallization method. CONCLUSIONS: The lftA gene cloned from A. ureafaciens
      K2032 encode a novel levan fructotransferase which produces difructose
      dianhydride (DFA IV) from levan. SIGNIFICANCE AND IMPACT OF THE STUDY: Levan
      fructotransferase is a useful enzyme with great promise in the production of DFA
      IV and various fructosides.

PMID- 15715651
TI  - Protective autoimmunity: interferon-gamma enables microglia to remove glutamate
      without evoking inflammatory mediators.
AB  - Glutamate in excessive amounts is a major contributor to neuronal degeneration,
      and its removal is attributed mainly to astrocytes. Traumatic injury to the
      central nervous system (CNS) is often accompanied by disappearance of astrocytes
      from the lesion site and failure of the remaining cells to withstand the ensuing
      toxicity. Microglia that repopulate the lesion site are the usual suspects for
      causing redox imbalance and inflammation and thus further exacerbating the
      neurotoxicity. However, our group recently demonstrated that early post-injury
      activation of microglia as antigen-presenting cells correlates with an ability to
      withstand injurious conditions. Moreover, we found that T cells reactive to CNS
      specific self-antigens protected neurons against glutamate toxicity. Here, we
      show that antigen-specific autoimmune T cells, by tailoring the microglial
      phenotype, can increase the ability of microglia-enriched cultures to remove
      glutamate. This T-cell-mediated effect could not be achieved by the potent
      microglia-activating agent lipopolysaccharide (LPS), but was dose-dependently
      reproduced by the Th1 cytokine interferon (IFN)-gamma and significantly reduced
      by neutralizing anti-IFN-gamma antibodies. Under the same conditions, IFN-gamma
      had no effect on cultured astrocytes. Up-regulation of glutamate uptake induced
      by IFN-gamma activation was not accompanied by the acute inflammatory response
      seen in LPS-activated cultures. These findings suggest that T cells or their
      cytokines can cause microglia to adopt a phenotype that facilitates rather than
      impairs glutamate clearance, possibly contributing to restoration of homeostasis.

PMID- 15715652
TI  - Aph-1 interacts at the cell surface with proteins in the active gamma-secretase
      complex and membrane-tethered Notch.
AB  - The activity of the gamma-secretase complex is critical for the processing of a
      number of transmembrane proteins, including Notch. Functional gamma-secretase
      activity can be reconstituted from four proteins--presenilin, nicastrin, Pen-2
      and Aph-1--but the role of the individual proteins remains unclear. In this
      report we describe the cellular localization and protein interactions of Aph-1,
      with particular regard to Notch receptor processing. We found that Aph-1 is
      present at the cell surface, where it interacts with Pen-2, the mature forms of
      presenilin and nicastrin, and full-length Notch. Aph-1 also interacts with a
      truncated form of Notch, which is a direct substrate for gamma-secretase, but not
      with the Notch intracellular domain. Immunoprecipitation data for Notch and Aph-1
      showed that the Notch-containing gamma-secretase complexes most likely form a
      small subset of the total number of gamma-secretase complexes. In conclusion,
      these data demonstrate that Aph-1 is present at the cell surface, presumably in
      active gamma-secretase complexes, and interacts with the Notch receptor, both
      before and after ligand activation.

PMID- 15715654
TI  - Pharmacological properties of homomeric and heteromeric pannexin hemichannels
      expressed in Xenopus oocytes.
AB  - Several new findings have emphasized the role of neuron-specific gap junction
      proteins (connexins) and electrical synapses in processing sensory information
      and in synchronizing the activity of neuronal networks. We have recently shown
      that pannexins constitute an additional family of proteins that can form gap
      junction channels in a heterologous expression system and are also widely
      expressed in distinct neuronal populations in the brain, where they may represent
      a novel class of electrical synapses. In this study, we have exploited the
      hemichannel-forming properties of pannexins to investigate their sensitivity to
      well-known connexin blockers. By combining biochemical and electrophysiological
      approaches, we report here further evidence for the interaction of pannexin1
      (Px1) with Px2 and demonstrate that the pharmacological sensitivity of
      heteromeric Px1/Px2 is similar to that of homomeric Px1 channels. In contrast to
      most connexins, both Px1 and Px1/Px2 hemichannels were not gated by external
      Ca2+. In addition, they exhibited a remarkable sensitivity to blockade by
      carbenoxolone (with an IC50 of approximately 5 microm), whereas flufenamic acid
      exerted only a modest inhibitory effect. The opposite was true in the case of
      connexin46 (Cx46), thus indicating that gap junction blockers are able to
      selectively modulate pannexin and connexin channels.

PMID- 15715655
TI  - Axonal transport of the cellular prion protein is increased during axon
      regeneration.
AB  - The cellular prion protein, PrPc, is a glycosylphosphatidylinositol-anchored cell
      surface glycoprotein and a protease-resistant conformer of the protein may be the
      infectious agent in transmissible spongiform encephalopathies. PrPc is localized
      on growing axons in vitro and along fibre bundles that contain elongating axons
      in developing and adult brain. To determine whether the growth state of axons
      influenced the expression and axonal transport of PrPc, we examined changes in
      the protein following post-traumatic regeneration in the hamster sciatic nerve.
      Our results show (1) that PrPc in nerve is significantly increased during nerve
      regeneration; (2) that this increase involves an increase in axonally transported
      PrPc; and (3) that the PrPc preferentially targeted for the newly formed portions
      of the regenerating axons consists of higher molecular weight glycoforms. These
      results raise the possibility that PrPc may play a role in the growth of axons in
      vivo, perhaps as an adhesion molecule interacting with the extracellular
      environment through specialized glycosylation.

PMID- 15715653
TI  - Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent
      iron toxicity in cells derived from the substantia nigra.
AB  - The role of dopamine in iron uptake into catecholaminergic neurons, and dopamine
      oxidation to aminochrome and its one-electron reduction in iron-mediated
      neurotoxicity, was studied in RCSN-3 cells, which express both tyrosine
      hydroxylase and monoamine transporters. The mean +/- SD uptake of 100 microm
      59FeCl3 in RCSN-3 cells was 25 +/- 4 pmol per min per mg, which increased to 28
      +/- 8 pmol per min per mg when complexed with dopamine (Fe(III)-dopamine). This
      uptake was inhibited by 2 microm nomifensine (43%p < 0.05), 100 microm imipramine
      (62%p < 0.01), 30 microm reboxetine (71%p < 0.01) and 2 mm dopamine (84%p <
      0.01). The uptake of 59Fe-dopamine complex was Na+, Cl- and temperature
      dependent. No toxic effects in RCSN-3 cells were observed when the cells were
      incubated with 100 microm FeCl3 alone or complexed with dopamine. However, 100
      microm Fe(III)-dopamine in the presence of 100 microm dicoumarol, an inhibitor of
      DT-diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited
      by 2 microm nomifensine, 30 microm reboxetine and 2 mm norepinephrine. The
      neuroprotective action of norepinephrine can be explained by (1) its ability to
      form complexes with Fe3+, (2) the uptake of Fe-norepinephrine complex via the
      norepinephrine transporter and (3) lack of toxicity of the Fe-norepinephrine
      complex even when DT-diaphorase is inhibited. These results support the proposed
      neuroprotective role of DT-diaphorase and norepinephrine.

PMID- 15715656
TI  - Control of death receptor and mitochondrial-dependent apoptosis by c-Jun N
      terminal kinase in hippocampal CA1 neurones following global transient ischaemia.
AB  - c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase
      family, is activated in response to a number of extracellular stimuli, including
      inflammatory cytokines, UV irradiation and ischaemia. A large body of evidence
      supports a role for JNK signalling in stress-induced apoptosis. It has been
      hypothesized that JNK may contribute to the apoptotic response by regulating the
      intrinsic cell death pathway involving the mitochondria. Here, we examined the
      role of the JNK signalling pathway in hippocampal CA1 apoptotic neurones
      following transient ischaemia in gerbils. We showed early activation of death
      receptor-dependent apoptosis (caspase-8 activation 2 days after ischaemia) and a
      biphasic activation of caspase-3 and caspase-9 after ischaemia. Activation of the
      mitochondrial pathway, as measured by cytochrome c release, appeared as a late
      event (5-7 days after ischaemia). AS601245, a novel JNK inhibitor, antagonized
      activation of both pathways and significantly protected CA1 neurones from cell
      death. Our results suggest a key role of JNK in the control of death receptor and
      mitochondrial-dependent apoptosis after transient ischaemia.

PMID- 15715657
TI  - Potentiation of ATP-induced currents due to the activation of P2X receptors by
      ubiquitin carboxy-terminal hydrolase L1.
AB  - Mammalian neuronal cells abundantly express a de-ubiquitinating isozyme,
      ubiquitin carboxy-terminal hydrolase L1 (UCH L1). Loss of UCH L1 function causes
      dying-back type of axonal degeneration. However, the function of UCH L1 in
      neuronal cells remains elusive. Here we show that overexpression of UCH L1
      potentiated ATP-induced currents due to the activation of P2X receptors that are
      widely distributed in the brain and involved in various biological activities
      including neurosecretion. ATP-induced inward currents were measured in mock-,
      wild-type or mutant (C90S)-UCH L1-transfected PC12 cells under the conventional
      whole-cell patch clamp configuration. The amplitude of ATP-induced currents was
      significantly greater in both wild-type and C90S UCH L1-transfected cells,
      suggesting that hydrolase activity was not involved but increased level of mono
      ubiquitin might play an important role. The increased currents were dependent on
      cAMP-dependent protein kinase (PKA) and Ca2+ and calmodulin-dependent protein
      kinase (CaMKII) but not protein kinase C. In addition, ATP-induced currents were
      likely to be modified via dopamine and cyclic AMP-regulated phosphoprotein (DARPP
      32) that is regulated by PKA and phosphatases. Our finding shows the first
      evidence that there is a relationship between UCH L1 and neurotransmitter
      receptor, suggesting that UCH L1 may play an important role in synaptic activity.

PMID- 15715658
TI  - LFRFamides: a novel family of parasitation-induced -RFamide neuropeptides that
      inhibit the activity of neuroendocrine cells in Lymnaea stagnalis.
AB  - We report the characterization of a cDNA encoding a novel -RFamide neuropeptide
      precursor that is up-regulated during parasitation in the snail Lymnaea
      stagnalis. Processing of this precursor yields five structurally related
      neuropeptides, all but one ending with the C-terminal sequence -LFRFamide, as was
      confirmed by direct mass spectrometry of brain tissue. The LFRFamide gene is
      expressed in a small cluster of neurons in each buccal ganglion, three small
      clusters in each cerebral ganglion, and one cluster in each lateral lobe of the
      cerebral ganglia. Application of two of the LFRFamide peptides to neuroendocrine
      cells that control either growth and metabolism or reproduction induced similar
      hyperpolarizing K+-currents, and inhibited electrical activity. We conclude that
      up-regulation of inhibitory LFRFamide neuropeptides during parasitation probably
      reflects an evolutionary adaptation that allows endoparasites to suppress host
      metabolism and reproduction in order to fully exploit host energy recourses.

PMID- 15715659
TI  - Cellular and subcellular calcium accumulation during glutamate-induced injury in
      cerebellar granule neurons.
AB  - Abstract We have investigated the role of Ca2+ accumulation and neuronal injury
      in cerebellar granule neurons after glutamate receptor overactivation. After the
      removal of the free cytosolic Ca2+ we identified an extensive second Ca2+
      fraction (SCF) that is retained within the neurons after glutamate receptor
      overactivation. The SCF reaches a plateau within 10 min with the magnitude of
      this SCF accumulation reflecting the extent of the neuronal injury that occurs
      within the neurons. The existence of this SCF is sensitive to both NMDA receptor
      antagonists and mitochondrial inhibitors but is unaffected by agents that deplete
      endoplasmic reticulum Ca2+, indicating that this Ca2+ fraction may be located
      within the mitochondria. Through the isolation of mitochondria from cerebellar
      granule neurons treated with glutamate we have shown that the majority of the SCF
      is mitochondrial in location. On the removal of the glutamate stimulus the SCF
      recovers at a slower rate than the free Ca2+ concentration within the neuron.
      This is intriguing, as it implies a capacity to remember previous excitatory
      events. Most significantly we have shown that a short pre-application of
      subthreshold glutamate or kainate blocks both SCF Ca2+ accumulation and extensive
      neuronal injury in response to high concentrations of glutamate. These findings
      may be relevant to the observations of pre-conditioning in the brain and heart.

PMID- 15715660
TI  - Glutathione depletion resulting in selective mitochondrial complex I inhibition
      in dopaminergic cells is via an NO-mediated pathway not involving peroxynitrite:
      implications for Parkinson's disease.
AB  - An early biochemical change in the Parkinsonian substantia nigra (SN) is
      reduction in total glutathione (GSH + GSSG) levels in affected dopaminergic
      neurons prior to depletion in mitochondrial complex I activity, dopamine loss,
      and cell death. We have demonstrated using dopaminergic PC12 cell lines
      genetically engineered to inducibly down-regulate glutathione synthesis that
      total glutathione depletion in these cells results in selective complex I
      inhibition via a reversible thiol oxidation event. Here, we demonstrate that
      inhibition of complex I may occur either by direct nitric oxide (NO) but not
      peroxinitrite-mediated inhibition of complex I or through H2O2-mediated
      inhibition of the tricarboxylic acid (TCA) cycle enzyme alpha-ketoglutarate
      dehydrogenase (KGDH) which supplies NADH as substrate to the complex; activity of
      both enzymes are reduced in PD. While glutathione depletion causes a reduction in
      spare KGDH enzymatic capacity, it produces a complete collapse of complex I
      reserves and significant effects on mitochondrial function. Our data suggest that
      NO is likely the primary agent involved in preferential complex I inhibition
      following acute glutathione depletion in dopaminergic cells. This may have major
      implications in terms of understanding mechanisms of dopamine cell death
      associated with PD especially as they relate to complex I inhibition.

PMID- 15715661
TI  - Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase
      kinase 3beta in SH-SY5Y neuroblastoma cells.
AB  - We have previously reported an aberrant accumulation of activated protein kinase
      B (PKB), glycogen synthase kinase (GSK)-3beta, extracellular signal-regulated
      kinase (ERK1/2), c-Jun N-terminal kinase (JNK), p38 and p70 S6 kinase (p70S6K) in
      neurons bearing neurofibrillary tangles (NFTs) in Alzheimer's disease (AD).
      However, the mechanism by which these tau candidate kinases are involved in the
      regulation of p70S6K and GSK-3beta phosphorylation is unknown. In the current
      study, 100 microM zinc sulfate was used, and influences of various components of
      phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK)
      pathways on p70S6K and GSK-3beta phosphorylation have been investigated in serum
      deprived SH-SY5Y neuroblastoma cells. We found that zinc could induce an increase
      of phosphorylated (p) p70S6K, p-PKB, p-GSK-3beta, p-ERK1/2, p-JNK and p-p38,
      especially in long-term treatment (4-8 h). Treatment with different inhibitors
      including rapamycin, wortmannin, LY294002, and U0126, and their combinations,
      indicated that phosphorylation of p70S6K and GSK-3beta is regulated by rapamycin
      dependent, PI3K and MAPK pathways. Furthermore, phosphorylation of p70S6K and GSK
      3beta affected levels of tau unphosphorylated at the Tau-1 site and
      phosphorylated at the PHF-1 site, and p70S6K phosphorylation affected the total
      tau level. Thus, 100 microM zinc might activate PKB, GSK-3beta, ERK1/2, JNK, p38
      and p70S6K, that are consequently involved in tau changes in SH-SY5Y cells.

PMID- 15715662
TI  - Molecular characterization of the family of choline transporter-like proteins and
      their splice variants.
AB  - We show here that the choline transporter-like (CTL) family is more extensive
      than initially described with five genes in humans and complex alternative
      splicing. In adult rat tissues, CTL2-4 mRNAs are mainly detected in peripheral
      tissues, while CTL1 is widely expressed throughout the nervous system. During rat
      post-natal development, CTL1 is expressed in several subpopulations of neurones
      and in the white matter, where its spatio-temporal distribution profile recalls
      that of myelin basic protein, an oligodendrocyte marker. We identified two major
      rat splice variants of CTL1 (CTL1a and CTL1b) differing in their carboxy-terminal
      tails with both able to increase choline transport after transfection in
      neuroblastoma cells. In the developing brain, CTL1a is expressed in both neurones
      and oligodendroglial cells, whereas CTL1b is restricted to oligodendroglial
      cells. These findings suggest specific roles for CTL1 splice variants in both
      neuronal and oligodendrocyte physiology.

PMID- 15715663
TI  - Differential regulation of multiple populations of granules in rat adrenal
      chromaffin cells by culture duration and cyclic AMP.
AB  - We employed carbon fiber amperometry to measure the amount of catecholamine
      released from individual granules (i.e. the quantal size, Q) of rat chromaffin
      cells. The distribution of Q1/3 of amperometric events could be reasonably
      described by the summation of at least three Gaussians, suggesting that rat
      chromaffin cells contained at least three distinct populations of granules, with
      a small, medium or large modal Q. After 3 days of culture, the mean cellular Q
      reduced by approximately 14%, which did not arise from a uniform percentage
      decrease in the Q of every granule. Instead, the rundown involved a > 11%
      decrease in the proportional release from large Q granules and a > 19% decrease
      in the modal Q-value of small Q granules. In contrast, when cells were cultured
      with dibutyryl-cAMP (dBcAMP) for 3 days, their mean cellular Q increased by
      approximately 38% (relative to time-matched controls). This increase in Q was not
      associated with any shift in the proportional release from the three populations
      of granules. Instead, cAMP increased the average amount of catecholamines
      released from all three populations of granules. Our data raise the possibility
      that distinct populations of granules in rat chromaffin cells can be regulated
      either differentially or uniformly.

PMID- 15715664
TI  - Identification of complement 5a-like receptor (C5L2) from astrocytes:
      characterization of anti-inflammatory properties.
AB  - Brain inflammation is regulated by endogenous substances, including
      neurotransmitters such as noradrenaline (NA), which can increase anti
      inflammatory genes. To identify NA-regulated, anti-inflammatory genes, we used
      TOGA (total gene expression analysis) to screen rat astrocyte-derived RNA. NA
      inducible cDNA clone DST11 encodes an isoform of the complement C5a receptor
      (C5aR), with 39% identity at the amino acid level to the rat C5aR, and 56%
      identity to a recently described human C5aR variant termed C5L2 (complement 5a
      like receptor). Quantitative PCR confirmed that in astrocytes, DST11 mRNA
      expression is increased by NA, whereas in vivo depletion of cortical NA reduced
      DST11 levels. Western blot analysis demonstrated basal and NA-induced expression
      of DST11 as a 45 kDa protein in primary astrocytes cultures. Immunocytochemical
      staining of adult rat brain revealed DST11-immunoreactivity throughout brain, co
      localized to neurons and astrocytes. In astrocytes, induction of nitric oxide
      synthase type 2 was increased by treatment with antisense oligonucleotides to
      DST11. Reducing DST11 expression also increased nuclear factor kappaB reporter
      gene, and decreased cAMP response element reporter gene activation. These results
      demonstrate that DST11 is a C5aR isoform expressed by glia and neurons, which is
      regulated by NA, and exerts anti-inflammatory functions. Changes in DST11 levels
      in diseased brain could therefore contribute to the progression of inflammatory
      damage.

PMID- 15715665
TI  - Sleep deprivation induces the unfolded protein response in mouse cerebral cortex.
AB  - Little is known about the molecular mechanisms underlying sleep. We show the
      induction of key regulatory proteins in a cellular protective pathway, the
      unfolded protein response (UPR), following 6 h of induced wakefulness. Using
      C57/B6 male mice maintained on a 12:12 light/dark cycle, we examined, in cerebral
      cortex, the effect of different durations of prolonged wakefulness (0, 3, 6, 9
      and 12 h) from the beginning of the lights-on inactivity period, on the protein
      expression of BiP/GRP78, a chaperone and classical UPR marker. BiP/GRP78
      expression is increased with increasing durations of sleep deprivation (6, 9 and
      12 h). There is no change in BiP/GRP78 levels in handling control experiments
      carried out during the lights-off period. PERK, the transmembrane kinase
      responsible for attenuating protein synthesis, which is negatively regulated by
      binding to BiP/GRP78, is activated by dissociation from BiP/GRP78 and by
      autophosphorylation. There is phosphorylation of the elongation initiation factor
      2alpha and alteration in ribosomal function. These changes are first observed
      after 6 h of induced wakefulness. Thus, prolonging wakefulness beyond a certain
      duration induces the UPR indicating a physiological limit to wakefulness.

PMID- 15715666
TI  - A domain at the C-terminus of PS1 is required for presenilinase and gamma
      secretase activities.
AB  - The structural requirements for presenilin (PS) to produce active presenilinase
      and gamma-secretase enzymes are poorly understood. Here we investigate the role
      the cytoplasmic C-terminal region of PS1 plays in PS1 activity. Deletion or
      addition of residues at the PS C-terminus has been reported to inhibit
      presenilinase endoproteolysis of PS and alter gamma-secretase activity. In this
      study, we use a sensitive assay in PS1/2KO MEFs to define a domain at the extreme
      C-terminus of PS1 that is essential for both presenilinase and gamma-secretase
      activities. Progressive deletion of the C-terminus demonstrated that removal of
      nine residues produces a PS1 molecule (458ST) that lacks both presenilinase
      processing and gamma-secretase cleavage of Notch and APP substrates. In contrast,
      removal of four or five residues had no effect (462ST, 463ST), while intermediate
      truncations partially inhibited PS1 activity. The 458ST mutant was unable to
      replace endogenous wtPS1 in HEK293 cells. Although 458ST was able to form a gamma
      secretase complex, this complex was not matured, illustrated by mutant PS1
      instability, lack of endoproteolysis, and little production of mature Nicastrin.
      These data indicate that the C-terminal end of PS1 is essential for Nicastrin
      trafficking and modification as well as the replacement of endogenous PS1 by PS1
      transgenes.

PMID- 15715667
TI  - Differences in serotonergic neurotransmission between rats displaying high or low
      anxiety/depression-like behaviour: effects of chronic paroxetine treatment.
AB  - Disturbances in serotonergic neurotransmission have been suggested to be closely
      interlinked with hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA)
      system, and are likely to be involved in the pathophysiology of anxiety disorders
      and major depression. We therefore investigated markers of serotonergic
      transmission and their modulation by chronic paroxetine in rats selectively bred
      for high (HAB) or low (LAB) anxiety-related behaviour, both under basal
      conditions and in response to emotional stress. Hippocampal serotonin 1 A (5
      HT1A) receptor mRNA expression was reduced in HAB rats, whereas 5-HT
      concentrations in hippocampal microdialysates did not differ between HAB and LAB
      rats under basal conditions. In the hippocampus, overall expression of serotonin
      transporter binding sites was increased in HAB compared with LAB rats. Exposure
      to emotional stress failed to increase intrahippocampal 5-HT release in HAB rats
      whereas LAB rats displayed a physiological, albeit small rise. Chronic paroxetine
      treatment markedly increased the stress-induced rise in hippocampal 5-HT in HAB,
      but not LAB rats. This effect may be (at least in part) related to a greater down
      regulation of hippocampal serotonin transporter binding sites by paroxetine in
      HABs compared with LABs, while 5-HT1A receptor expression remained unaffected in
      this brain area. The findings indicate reduced hippocampal serotonergic
      transmission in HAB rats as compared with LAB rats, which is evident both at the
      presynaptic (5-HT release) and the postsynaptic (5-HT1A receptor) level. Chronic
      paroxetine enhanced the presynaptic responsivity in HAB rats, but not LAB rats,
      pointing to a preferential efficacy of paroxetine in rats with enhanced
      anxiety/depression-related behaviour.

PMID- 15715668
TI  - A complementary peptide approach applied to the design of novel
      semaphorin/neuropilin antagonists.
AB  - Semaphorin 3A can inhibit axonal growth and induce neuronal apoptosis following
      binding to neuropilin-1, with the membrane proximal MAM (meprin, A5, mu) domain
      in neuropilin-1 playing a key role in the formation of a higher order receptor
      complex. If functional motifs on semaphorin 3A and/or the MAM domain can be
      identified, then small-constrained peptides might be developed as antagonists. We
      have scored peptide pairs for complementary hydropathy and antisense homology to
      identify a candidate functional motif in the Ig domain of semaphorin 3A, and in
      the MAM domain of neuropilin-1. Synthetic peptides corresponding to these
      sequences fully inhibit growth cone collapse induced by semaphorin 3A. A number
      of smaller peptides derived from the parental sequence also inhibited the
      response, particularly after they were constrained by a disulfide bond. Finally,
      we have used an algorithm to design a peptide that is a near-perfect hydropathic
      complement of the candidate functional site in the MAM domain; this also inhibits
      the semaphorin 3A response. Thus, an algorithm-driven methodology has led to the
      identification of three independent semaphorin 3A antagonists. Semaphorin 3F
      stimulates growth cone collapse following binding to the closest relative to
      neuropilin-1 in the genome, neuropilin-2. Where tested, the peptides that
      antagonise semaphorin 3A failed to inhibit the semaphorin 3F response.

PMID- 15715670
TI  - Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar
      granule cells and astrocytes.
AB  - Sphingosine-1-phosphate (S1P) is a potent biomediator that can act as either an
      intracellular or an intercellular messenger. In the nervous system it exerts a
      wide range of actions, and specific membrane receptors for it have been
      identified in various regions. However, the physiological origin of extracellular
      S1P in the nervous system is largely unknown. We investigated cerebellar granule
      cells at different stages of differentiation and astrocytes in primary cultures
      as possible origins of extracellular S1P. Although these cells show marked
      differences in S1P metabolism, we found that they can all release S1P and express
      mRNAs for S1P specific receptors. Extracellular S1P derives from the export of
      newly synthesized intracellular S1P, and not from the action of a released
      sphingosine kinase. S1P release is rapid, efficient, and can be regulated by
      exogenous stimuli. Phorbol ester treatment resulted in an increase in sphingosine
      kinase 1 activity in the membranes, accompanied by a significant increase in
      extracellular S1P. S1P release in cells from the cerebellum emerges as a
      regulated mechanism, possibly related to a specific pool of newly synthesized
      S1P. To our knowledge, this is the first evidence of the extracellular release of
      S1P by primary cells from the CNS, which supports a role of S1P as
      autocrine/paracrine physiological messenger in the cerebellum.

PMID- 15715669
TI  - Process elongation of oligodendrocytes is promoted by the Kelch-related actin
      binding protein Mayven.
AB  - Rearrangement of the cytoskeleton leading to the extension of cellular processes
      is essential for the myelination of axons by oligodendrocytes. We observed that
      the actin-binding protein, Mayven, is expressed during all stages of the
      oligodendrocyte lineage, and that its expression is up-regulated during
      oligodendrocyte differentiation. Mayven is localized in the cytoplasm and along
      the cell processes. Mayven also binds actin, and is involved in the cytoskeletal
      reorganization in oligodendrocyte precursor cells (O-2A cells) that leads to
      process elongation. Mayven overexpression resulted in an increase in the process
      outgrowth of O-2A cells and in the lengths of the processes, while microinjection
      of Mayven-specific antibodies inhibited process extension in these cells.
      Furthermore, O-2A cells transduced with recombinant retroviral sense Mayven (pMIG
      W-Mayven) showed an increase in the number of oligodendrocyte processes with
      outgrowth, while recombinant retroviral antisense Mayven (pMIG-W-Mayven-AS)
      blocked O-2A process extension. Interestingly, co-localization and association of
      Mayven with Fyn kinase were found in O-2A cells, and these interactions were
      increased during the outgrowth of oligodendrocyte processes. This association was
      mediated via the SH3 domain ligand (a.a. 1-45) of Mayven and the SH3 domain of
      Fyn, suggesting that Mayven may act as a linker to bind Fyn, via its N-terminus.
      Thus, Mayven plays a role in the dynamics of cytoskeletal rearrangement leading
      to the process extension of oligodendrocytes.

PMID- 15715671
TI  - Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate
      plasma acetylcholinesterase and paraoxonase activities.
AB  - The 5.5 Mb chromosome 7q21-22 ACHE/PON1 locus harbours the ACHE gene encoding the
      acetylcholine hydrolyzing, organophosphate (OP)-inhibitable acetylcholinesterase
      protein and the paraoxonase gene PON1, yielding the OP-hydrolyzing PON1 enzyme
      which also displays arylesterase activity. In search of inherited and acquired
      ACHE-PON1 interactions we genotyped seven polymorphic sites and determined the
      hydrolytic activities of the corresponding plasma enzymes and of the AChE
      homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE,
      arylesterase, BChE and paraoxonase activities in plasma displayed 5.4-, 6.5-, 7.2
      and 15.5-fold variability, respectively, with genotype-specific differences
      between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase
      but not paraoxonase activity increased with age, depending on leucine at PON1
      position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase
      activity independent of the - 108 promoter polymorphism. Predicted structural
      consequences of the PON1 L55M substitution demonstrated spatial shifts in
      adjacent residues. Molecular modelling showed substrate interactions with the
      enzyme variants, explaining the changes in substrate specificity induced by the
      Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities
      displayed inverse association with AChE activity. Our findings demonstrate that
      polymorphism(s) in the adjacent PON1 and ACHE genes affect each other's
      expression, predicting for carriers of biochemically debilitating ACHE/PON1
      polymorphisms adverse genome-environment interactions.

PMID- 15715673
TI  - In vivo gene silencing of CD81 by lentiviral expression of small interference
      RNAs suppresses cocaine-induced behaviour.
AB  - The tetraspanin CD81 is induced in the mesolimbic dopaminergic pathway after
      cocaine administration. To further investigate its role, a regulatable lentivirus
      (Lenti-CD81) bearing the CD81 gene under the control of a tetracycline-inducible
      promoter and lentiviruses expressing short hairpin RNA (shRNA) targeted against
      CD81 (Lenti-CD81-shRNAs) have been prepared. Infection of HEK293T cells in vitro
      with Lenti-CD81-shRNAs resulted in 96.5% gene silencing (from quantitative real
      time PCR(qRT-PCR) and immunocytochemistry). In vivo delivery of Lenti-CD81-shRNA
      into the nucleus accumbens or ventral tegmental area resulted in 91.3 and 94%
      silencing of endogenous CD81, respectively. Stereotaxic injection of Lenti-CD81
      into these regions, resulting in CD81 overexpression, induced a four- to fivefold
      increase in locomotor activity after chronic cocaine administration, which
      returned to basal levels when Lenti-CD81-shRNA had been coinjected or when CD81
      expression was blocked by doxycycline. Furthermore, silencing endogenous CD81 in
      vivo resulted in a significant decrease in locomotor activity over controls,
      again suppressing cocaine-induced behaviour.

PMID- 15715672
TI  - Role of the autophagic-lysosomal system on low potassium-induced apoptosis in
      cultured cerebellar granule cells.
AB  - Apoptotic and autophagic cell death have been implicated, on the basis of
      morphological and biochemical criteria, in neuronal loss occurring in
      neurodegenerative diseases and it has been shown that they may overlap. We have
      studied the relationship between apoptosis and autophagic cell death in
      cerebellar granule cells (CGCs) undergoing apoptosis following serum and
      potassium deprivation. We found that apoptosis is accompanied by an early and
      marked proliferation of autophagosomal-lysosomal compartments as detected by
      electron microscopy and immunofluorescence analysis. Autophagy is blocked by
      hrIGF-1 and forskolin, two well-known inhibitors of CGC apoptosis, as well as by
      adenovirus-mediated overexpression of Bcl-2. 3-Methyladenine (3-MA) an inhibitor
      of autophagy, not only arrests this event but it also blocks apoptosis. The
      neuroprotective effect of 3-MA is accompanied by block of cytochrome c (cyt c)
      release in the cytosol and by inhibition of caspase-3 activation which, in turn,
      appears to be mediated by cathepsin B, as CA074-Me, a selective inhibitor of this
      enzyme, fully blocks the processing of pro-caspase-3. Immunofluorescence analysis
      demonstrated that cathepsin B, normally confined inside the lysosomal-endosomal
      compartment, is released during apoptosis into the cytosol where this enzyme may
      act as an execution protease. Collectively, these observations indicate that
      autophagy precedes and is causally connected with the subsequent onset of
      programmed death.

PMID- 15715674
TI  - Mutagenesis studies of conserved proline residues of human P2X receptors for ATP
      indicate that proline 272 contributes to channel function.
AB  - Proline residues can play a major role in the secondary structure of proteins. In
      the extracellular ATP binding loop of P2X receptors there are four totally
      conserved proline residues (P2X1 receptor numbering; P93, P166, P228 and P272)
      and three less conserved residues P196 (six of seven isoforms), P174 and P225
      (five of seven isoforms). We have mutated individual conserved proline residues
      in the human P2X1 receptor and determined their properties. Mutants were
      expressed in Xenopus oocytes and characterized using a two-electrode voltage
      clamp. Mutants P166A, P174A, P196A, P225A and P228A had no effect on ATP potency
      compared with wild-type and P93A had a fourfold decrease in ATP potency. The
      P272A, P272D and P272K receptor mutants were expressed at the cell surface;
      however, these mutants were non-functional. In contrast, P272I, P272G and P272F
      produced functional channels, with either no effect or a 2.5- or 6.5-fold
      increase in ATP potency, respectively. At P272F receptors the apparent affinity
      of the ATP analogue antagonist 2',3'-O-(2,4,6-trinitrophenyl)-ATP was increased
      by 12.5-fold. These results suggest that individual proline residues are not
      essential for normal P2X receptor function and that the receptor conformation
      around P272 contributes to ATP binding at the receptor.

PMID- 15715676
TI  - Retinal-specific ATP-binding cassette transporter (ABCR/ABCA4) is expressed at
      the choroid plexus in rat brain.
AB  - ATP-binding cassette (ABC) transporter A4 is a member of the ABC transporter
      subfamily A which has been reported to be exclusively expressed in the retina. In
      contrast, a previous report has suggested a possible relationship between ABCA4
      and CNS function. The purpose of the present study was to investigate the
      localization of ABCA4 mRNA and protein in rat brain. In situ hybridization
      analysis revealed that ABCA4 mRNA was localized in the lateral ventricles. RT-PCR
      analysis detected ABCA4 mRNA in isolated rat choroid plexus and conditionally
      immortalized rat choroid plexus epithelial cells (TR-CSFB). Furthermore, ABCA4
      protein was also detected in the isolated rat choroid plexus at about 250 kDa by
      western blot analysis, and its apparent molecular size was reduced by N
      glycosidase F treatment. These results suggest that glycosylated ABCA4 protein is
      expressed in rat choroid plexus epithelial cells. ABCA4 may play a role in the
      function of the blood-cerebrospinal fluid barrier and affect CSF conditions.

PMID- 15715675
TI  - In vitro and in vivo analyses of human embryonic stem cell-derived dopamine
      neurons.
AB  - Human embryonic stem (hES) cells, due to their capacity of multipotency and self
      renewal, may serve as a valuable experimental tool for human developmental
      biology and may provide an unlimited cell source for cell replacement therapy.
      The purpose of this study was to assess the developmental potential of hES cells
      to replace the selectively lost midbrain dopamine (DA) neurons in Parkinson's
      disease. Here, we report the development of an in vitro differentiation protocol
      to derive an enriched population of midbrain DA neurons from hES cells. Neural
      induction of hES cells co-cultured with stromal cells, followed by expansion of
      the resulting neural precursor cells, efficiently generated DA neurons with
      concomitant expression of transcriptional factors related to midbrain DA
      development, such as Pax2, En1 (Engrailed-1), Nurr1, and Lmx1b. Using our
      procedure, the majority of differentiated hES cells (> 95%) contained neuronal or
      neural precursor markers and a high percentage (> 40%) of TuJ1+ neurons was
      tyrosine hydroxylase (TH)+, while none of them expressed the undifferentiated ES
      cell marker, Oct 3/4. Furthermore, hES cell-derived DA neurons demonstrated
      functionality in vitro, releasing DA in response to KCl-induced depolarization
      and reuptake of DA. Finally, transplantation of hES-derived DA neurons into the
      striatum of hemi-parkinsonian rats failed to result in improvement of their
      behavioral deficits as determined by amphetamine-induced rotation and step
      adjustment. Immunohistochemical analyses of grafted brains revealed that abundant
      hES-derived cells (human nuclei+ cells) survived in the grafts, but none of them
      were TH+. Therefore, unlike those from mouse ES cells, hES cell-derived DA
      neurons either do not survive or their DA phenotype is unstable when grafted into
      rodent brains.

PMID- 15715678
TI  - Blood coagulation and its regulation by anticoagulant pathways: genetic
      pathogenesis of bleeding and thrombotic diseases.
AB  - Blood coagulation and its regulation by anticoagulant pathways: genetic
      pathogenesis Platelet-mediated primary haemostasis and blood coagulation have
      evolved as important defence mechanisms against bleeding. The formation of the
      platelet plug provides the initial occlusion of the vascular lesion. This is
      temporally co-ordinated with the activation of the coagulation system, which
      occurs in response to the rupture of endothelium and the exposure of blood to the
      extravascular tissue. The reactions of blood coagulation are carefully controlled
      by several anticoagulant mechanisms and under normal conditions they prevail over
      the procoagulant forces. Genetic or acquired disturbances of the natural balance
      between the pro- and anticoagulant systems may result in bleeding or thrombotic
      diseases.

PMID- 15715677
TI  - Increased cyclin E expression may obviate the role of cyclin D1 during brain
      development in cyclin D1 knockout mice.
AB  - Cyclins D and E play critical roles during the G1 phase of mammalian cell
      division. Cyclin D1 expression is high and expected to play an important role
      during mouse brain development. However, in the present study, we found no
      difference in CNS morphology between cyclin D1 knockout (KO) and control wild
      type mice at the ages of 1, 4 and 12 months. Analysis of protein expression in
      embryonic brains revealed that cyclin E is obviously increased in cyclin D1 KO
      mice at 13.5 days post coitum. At the same age a high level of cyclin D1
      expression is detected in the embryonic brain of wild-type mice. The data
      indicate that enhanced cyclin E protein expression in cyclin D1 KO mice may
      obviate the role of cyclin D1 and contribute to the normal brain development of
      cyclin D1 KO mice.

PMID- 15715679
TI  - Pathogen inactivation technology: cleansing the blood supply.
AB  - The calculated residual infectious risk of HIV, hepatitis B virus (HBV) and
      hepatitis C virus (HCV) from blood transfusion is extremely low. However, the
      risk of bacterial contamination remains and a variety of other agents including
      emerging viruses, protozoa and tick-borne agents threaten blood supplies and
      undermine public confidence in blood safety. Traditional methods of donor
      screening and testing have limited ability to further reduce disease transmission
      and cannot prevent an emerging infectious agent from entering the blood supply.
      Pathogen inactivation technologies have all but eliminated the infectious risks
      of plasma-derived protein fractions, but as yet no technique has proved
      sufficiently safe and effective for traditional blood components. Half-way
      technologies can reduce the risk of pathogen transmission from fresh frozen
      plasma and cryoprecipitate. Traditional methods of mechanical removal such as
      washing and filtration have limited success in reducing the risk of cell
      associated agents, but methods aimed at sterilizing blood have either proved
      toxic to the cells or to the recipients of blood components. Several promising
      methods that target pathogen nucleic acid have recently entered clinical testing.

PMID- 15715680
TI  - Relationship of QT interval duration with carotid intima media thickness in a
      clinically healthy population undergoing cardiovascular risk screening.
AB  - OBJECTIVES: To investigate the relationship between cardiac repolarization (QT
      interval duration) and intima media thickness (IMT) of the carotid arteries as
      surrogate measures of subclinical atherosclerosis. DESIGN: Prospective study with
      consecutive subjects enrolled in the SAPHIR program (Salzburg Atherosclerosis
      Prevention Program in Subjects at High Individual Risk). SETTING: The analysis of
      the material was performed at the departments of medicine and neurology of a
      university hospital. SUBJECTS: The study cohort comprises a population-based
      sample of 1199 clinically healthy subjects (851 men and 348 women; age 39-66
      years). Exclusion criteria were cardiovascular disease, diabetes, atrial
      fibrillation, bundle branch block and use of medication affecting QT interval
      duration. MAIN OUTCOME MEASURES: IMT of common (CCA) and internal carotid
      arteries (ICA) was measured by B-mode ultrasound. QT interval duration was
      determined in the resting 12-lead electrocardiogram by an automatic analysis
      program. The QT intervals were corrected for heart rate with five standard
      equations (QTc-Bazett, -Fridericia, -Framingham, -Hodges and -Rautaharju) and
      tested for their relationship with carotid IMT after adjustment for clinical and
      metabolic variables. Results. Females had higher heart rates than males (64 +/-
      10 b min(-1) vs. 60 +/- 9 b min(-1), P <0.0005), with longer mean QT (410 +/- 28
      ms vs. 404 +/- 28 ms, P=0.003) and QTc intervals in all correction formulae (P
      <0.0005). Significant correlations between QT/QTc and ICA IMT (r=0.14-0.16) were
      found in males. In the general linear model the association between QTc (except
      for Bazett) and ICA IMT remained significant after adjusting for age, BMI and
      further cardiovascular risk factors. In females the crude correlations between
      QT/QTc and ICA IMT were lower than those with CCA IMT. Only the correlation
      between uncorrected QT and CCA IMT (r=0.15, P=0.006) remained significant after
      adjustment for covariates. CONCLUSIONS: The results of the present study
      demonstrate that QT and QTc prolongation are in part associated with IMT of
      carotid arteries, which is an established risk marker of subclinical
      atherosclerosis. In men the data support the hypothesis of an association between
      QTc and ICA IMT. In women a statistically significant relationship was found
      between the uncorrected QT interval and CCA IMT. These findings suggest that
      differences in carotid IMT and ventricular repolarization between genders might
      be related to hormonal and nonhormonal effects.

PMID- 15715681
TI  - Difference in survival after out-of-hospital cardiac arrest between the two
      largest cities in Sweden: a matter of time?
AB  - BACKGROUND: Dramatic differences in survival after out-of-hospital cardiac
      arrests (OHCA) reported from different geographical locations require analysis.
      We therefore compared patients with OHCA in the two largest cities in Sweden with
      regard to various factors at resuscitation and outcome. SETTING: All patients
      suffering an OHCA in Stockholm and Goteborg between 1 January 2000 and 30 June
      2001, in whom cardiopulmonary resuscitation (CPR) was attempted were included in
      this retrospective analysis. RESULTS: All together, 969 OHCA in Stockholm and 398
      in Goteborg were registered during the 18-month study period. There were no
      differences in terms of age, gender, and percentage of witnessed cases or
      percentage of patients who had received bystander CPR. However, the percentage of
      patients with ventricular fibrillation (VF) at arrival of the ambulance crew was
      18% in Stockholm versus 31% in Goteborg (P <0.0001). The percentage of patients
      who were alive 1 month after cardiac arrest was 2.5% in Stockholm versus 6.8% in
      Goteborg (P=0.0008). Various time intervals such as cardiac arrest to calling for
      an ambulance, cardiac arrest to the start of CPR and calling for an ambulance to
      its arrival were all significantly longer in Stockholm than in Goteborg.
      CONCLUSION: Survival was almost three times higher in Goteborg than in Stockholm
      amongst patients suffering an OHCA. This is primarily explained by a higher
      occurrence of VF at the time of arrival of the ambulance crew, which in turn
      probably is explained by shorter delays in Goteborg. The reason for the
      difference in time intervals is most likely multifactorial, with a significantly
      higher ambulance density in Goteborg as one possible explanation.

PMID- 15715682
TI  - Homocysteine as a risk factor for CVD mortality in men with other CVD risk
      factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.
AB  - OBJECTIVE: Based on case-control and prospective studies elevated blood total
      homocysteine (tHcy) has been suggested to be an independent risk factor for
      cardiovascular diseases (CVD). The purpose of the study was to explore the joint
      effect of increased serum tHcy concentration and other risk factors on the risk
      of CVD mortality in middle-aged men without a history of heart disease or stroke.
      DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk
      Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged
      46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event.
      RESULTS: The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3).
      During the average follow-up time of 10.8 years 50 men experienced a CVD death.
      The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02
      3.19) in men in the highest serum tHcy third versus lower thirds after adjustment
      for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration
      appeared to increase the risk of CVD death in men who smoke or who have high
      circulating concentrations of serum total or LDL cholesterol, apo-B
      apolipoprotein or plasma fibrinogen. CONCLUSION: We conclude that homocysteine
      may increase the risk of CVD mortality in middle-aged men from Eastern Finland,
      and it may especially increase the risk when present with other risk factors for
      CVD.

PMID- 15715683
TI  - Endothelin receptor blockade improves endothelial function in atherosclerotic
      patients on angiotensin converting enzyme inhibition.
AB  - OBJECTIVES: Endothelin-1 (ET-1) and angiotensin II may contribute to endothelial
      dysfunction, which is associated with increased risk of events in patients with
      coronary artery disease. The objective was to test whether dual ETA/ETB receptor
      antagonism improves endothelium-dependent vasodilatation (EDV) in atherosclerotic
      patients, also on treatment with angiotensin converting enzyme (ACE) inhibitor.
      DESIGN AND SETTING: EDV and endothelium-independent vasodilatation were
      determined in 37 patients with atherosclerosis during measurement of forearm
      blood flow (FBF) with venous occlusion plethysmography. The patients were then
      randomized to treatment with ramipril 10 mg o.d. (n=21) or placebo (n=16) for 3
      months in a double-blind fashion. RESULTS: Intra-arterial infusion of the ETA
      receptor antagonist BQ123 and the ETB receptor antagonist BQ788 (both 10 nmol
      min(-1)) increased basal FBF by 42 +/- 4% (P <0.001) and enhanced EDV (P <0.001).
      Following 3 months ramipril treatment, ET receptor blockade still enhanced EDV.
      Acetylcholine 10 and 30 mg min(-1) increased FBF by 68 +/- 12 and 64 +/- 12 mL
      min(-1)/1000 mL before vs. 101 +/- 17 and 101 +/- 16 mL min(-1)/1000 mL following
      ET receptor blockade in the ramipril group (P <0.001). CONCLUSIONS: Dual ETA/ETB
      receptor blockade improves endothelial function and exerts direct vasodilator
      effects in patients with atherosclerosis, also on treatment with ramipril
      suggesting that ET receptor blockade may have important therapeutic effects when
      added to ACE inhibition in these patients.

PMID- 15715684
TI  - The Pro387Leu variant of protein tyrosine phosphatase-1B is not associated with
      diabetes mellitus type 2 in a German population.
AB  - OBJECTIVES: Diabetes mellitus type 2 (DM-2) is a complex disorder with a strong
      genetic background. Protein tyrosine phosphatase-1B (PTP-1B) dephosphorylates
      various receptor protein kinases in vitro, including the beta subunit of the
      insulin receptor, therefore representing a potential candidate to be involved in
      the polygenic pathogenesis of DM-2. Recently a Pro387Leu variant of the PTP-1B
      gene has been associated with an increased risk of DM-2 in a Danish population.
      Reports from China and Finland failed to confirm this association. DESIGN,
      SETTING AND SUBJECTS: The purpose of the present study was to examine the
      possible association between the presence of DM-2 and the Pro387Leu polymorphism
      in a German Caucasian population. A total of 836 subjects (age 20-92 years)
      participated in the study. The presence of the Pro387Leu variant of the PTP-1B
      gene was investigated using polymerase chain reaction (PCR) restriction fragment
      length polymorphism in 402 subjects with DM-2 (231 men, 171 women, age 63.1 +/-
      10.8 years, BMI 28.7 +/- 5.1 kg m(-2)) and in 434 normoglycemic age- and sex
      matched control subjects (248 men, 186 women, age 64.4 +/- 6.5 years, BMI 26.5 +/
      3.7 kg m(-2)). RESULTS: Nine subjects in the control group and nine in the
      diabetic group (allelic frequency 0.99% in both groups) carried the Pro387Leu
      polymorphism. A meta-analysis on published data of >3000 subjects including our
      own data did not find an association between the polymorphism and DM-2. In
      addition, the polymorphism had no significant influence on the presence of
      atherosclerotic disease, whilst the influence of other known cardiovascular risk
      factors was confirmed. Furthermore, the impact of the mutation on metabolic and
      anthropometric parameters in both groups was examined. Amongst the controls there
      were no significant differences in BMI, HDL and LDL cholesterol or blood pressure
      between the two groups with or without the Pro387Leu polymorphism. The same was
      true for the diabetic group. Interestingly, in both diabetics and controls,
      Pro387Leu carriers had significantly higher triglycerides. In a logistic
      regression model only BMI and family history but not polymorphism were predictors
      of DM-2. CONCLUSIONS: In conclusion, the present data suggest that in a German
      Caucasian population the Pro387Leu polymorphism of the PTP-1B gene is not
      associated with DM-2 but may play a role in other metabolic phenotypes.

PMID- 15715685
TI  - Nt-proANP in plasma, a marker of salt sensitivity, is reduced in type 2 diabetes
      patients.
AB  - OBJECTIVE: We recently showed that plasma concentration of N-terminal atrial
      natriuretic peptide (Nt-proANP) is strongly directly related to salt sensitivity.
      The aims of the present study were to test (i) whether plasma concentration of N
      terminal brain natriuretic peptide (Nt-proBNP) is related to salt sensitivity and
      (ii) whether Nt-proANP, as a marker of salt sensitivity, differs between type 2
      diabetes patients and nondiabetic subjects without a history of coronary heart
      disease. METHODS: Nt-proBNP was determined in 30 Swedish normal subjects with
      heredity for primary hypertension and salt sensitivity was defined as the
      difference between mean arterial blood pressure after 1 week on a high-salt diet
      (240 mmol day(-1)) and 1 week on a low-salt diet (10 mmol day(-1)). Nt-proANP was
      measured in 253 patients with type 2 diabetes and in 230 nondiabetic subjects
      aged 40-70 years, all without a history of coronary heart disease. RESULTS:
      Amongst the 30 subjects, in whom salt sensitivity was directly measured, Nt
      proBNP was not correlated with salt sensitivity (R=-0.18, P=0.35). Nt-proANP
      (median, interquartile range) was lower in patients with type 2 diabetes (505,
      387-661 pmol L(-1)) than in nondiabetic subjects (536, 421-696 pmol L(-1))
      (P=0.02). In a multiple regression analysis heart rate (P <0.00001), diastolic
      blood pressure (P=0.02) and diabetes status (P=0.02) were inversely related
      whereas age (P <0.00001), cystatin C (P=0.0006), hypertension treatment (P=0.002)
      and female sex (P=0.006) were directly related to ln(Nt-proANP). CONCLUSION: In
      contrast to Nt-proANP, Nt-proBNP is not related to salt sensitivity. Salt
      sensitivity, as estimated by Nt-proANP, seems to be reduced in type 2 diabetes.

PMID- 15715686
TI  - Holotranscobalamin--a first choice assay for diagnosing early vitamin B
      deficiency?
AB  - OBJECTIVES: The performance of holotranscobalamin (holoTC) was compared with the
      other markers of vitamin B12 deficiency, and the influence of age, renal
      function, and thyroid status was examined. DESIGN AND INTERVENTIONS: We examined
      937 individuals not treated with vitamin B12 but in whom vitamin B12 deficiency
      was suspected because of a plasma methylmalonic acid (MMA) above 0.28 micromol L(
      1) within the past 4 years. Besides laboratory tests, a structured interview and
      a neurological examination were performed amongst 534 individuals. Amongst these,
      140 individuals qualified for a randomized trial (MMA 0.40-2.00 micromol L(-1)).
      They were randomized to injections with vitamin B12 or placebo and re-examined
      after 3 months. SETTING: One university hospital in Aarhus, Denmark. RESULTS: The
      ROC curves indicate that holoTC (AUC: 0.90) compared favourable with plasma
      vitamin B12 (AUC: 0.85) for identifying individuals likely to have vitamin B12
      deficiency (MMA > or =0.75 micromol L(-1) and plasma total homocysteine (tHcy) >
      or =15 micromol L(-1)), and further that holoTC (AUC: 0.91) might replace
      combined testing with plasma vitamin B12 and the metabolites. No association was
      observed between the biochemical markers and symptoms and signs possibly related
      to vitamin B12 deficiency. HoloTC, TC saturation, plasma vitamin B12, MMA, and
      tHcy were significantly associated with plasma creatinine (all with P <0.001).
      Only tHcy was significantly associated with thyroid stimulating hormone (P=0.02).
      CONCLUSIONS: HoloTC shows promise as first-line tests for diagnosing early
      vitamin B12 deficiency.

PMID- 15715687
TI  - Chronic fatigue syndrome: assessment of increased oxidative stress and altered
      muscle excitability in response to incremental exercise.
AB  - OBJECTIVES: Because the muscle response to incremental exercise is not well
      documented in patients suffering from chronic fatigue syndrome (CFS), we combined
      electrophysiological (compound-evoked muscle action potential, M wave), and
      biochemical (lactic acid production, oxidative stress) measurements to assess any
      muscle dysfunction in response to a routine cycling exercise. DESIGN: This case
      control study compared 15 CFS patients to a gender-, age- and weight-matched
      control group (n=11) of healthy subjects. INTERVENTIONS: All subjects performed
      an incremental cycling exercise continued until exhaustion. MAIN OUTCOME
      MEASURES: We measured the oxygen uptake (VO2), heart rate (HR), systemic blood
      pressure, percutaneous O2 saturation (SpO2), M-wave recording from vastus
      lateralis, and venous blood sampling allowing measurements of pH (pHv), PO2
      (PvO2), lactic acid (LA), and three markers of the oxidative stress
      (thiobarbituric acid-reactive substances, TBARS, reduced glutathione, GSH, and
      ascorbic acid, RAA). RESULTS: Compared with control, in CFS patients (i) the
      slope of VO2 versus work load relationship did not differ from control subjects
      and there was a tendency for an accentuated PvO2 fall at the same exercise
      intensity, indicating an increased oxygen uptake by the exercising muscles; (ii)
      the HR and blood pressure responses to exercise did not vary; (iii) the anaerobic
      pathways were not accentuated; (iv) the exercise-induced oxidative stress was
      enhanced with early changes in TBARS and RAA and enhanced maximal RAA
      consumption; and (v) the M-wave duration markedly increased during the recovery
      period. CONCLUSIONS: The response of CFS patients to incremental exercise
      associates a lengthened and accentuated oxidative stress together with marked
      alterations of the muscle membrane excitability. These two objective signs of
      muscle dysfunction are sufficient to explain muscle pain and postexertional
      malaise reported by our patients.

PMID- 15715688
TI  - Impact of adiposity on carotid atherosclerosis in Japanese males with metabolic
      syndrome.

PMID- 15715689
TI  - Risk for fatal statin-induced rhabdomyolysis as a consequence of
      misinterpretation of 'evidence-based medicine'.

PMID- 15715690
TI  - Lack of evidence for interaction between APM1 and PPARgamma2 genes in modulating
      insulin sensitivity in nondiabetic Caucasians from Italy.

PMID- 15715691
TI  - Development of a condition-specific measure of quality of life for children with
      cerebral palsy: empirical thematic data reported by parents and children.
AB  - BACKGROUND: Although there is increasing recognition that quality of life (QOL)
      and health-related quality of life (HRQOL) are important outcome variables in
      clinical trials for children with cerebral palsy, there are substantial
      limitations in existing measures of QOL. This study identify themes of QOL for
      children with cerebral palsy and their parents to guide the development of a new
      condition-specific QOL scale. METHODS: A qualitative study of parent and child
      views on QOL composition was conducted, using a grounded theory framework.
      Families participated in semistructured interviews on QOL until thematic
      saturation was reached (n = 28 families). RESULTS: Overall, 13 themes emerged
      from the interviews: physical health, body pain and discomfort, daily living
      tasks, participation in regular physical and social activities, emotional well
      being and self-esteem, interaction with the community, communication, family
      health, supportive physical environment, future QOL, provision of, and access to
      services, financial stability, and social well-being. CONCLUSIONS: Research with
      parents and children with cerebral palsy, representative of severity across the
      disease spectrum and socio-economic status, reinforced and expanded on the
      traditional themes that have underpinned QOL measurement development. This has
      implications not only for the development of a new QOL scale for children with
      cerebral palsy, but also for clinical interventions and community care
      management.

PMID- 15715692
TI  - Mothers' perceptions of children's quality of life following early diagnosis and
      treatment for retinoblastoma (Rb).
AB  - We describe the Quality of Life (QoL) and IQ of survivors of retinoblastoma (Rb),
      both in relation to the normal population and between subgroups of Rb patients
      differing in relative risk (i.e. unilateral vs. bilateral disease). The sample
      included 54 children (28 males, age-range 8-16 years) and their mothers. Mothers
      completed standardized questionnaires to report their own QoL and that of their
      child. Children completed a brief IQ test. Compared with population norms,
      mothers reported lower levels of QoL for their child on total QoL and for sub
      scales measuring Physical and Psychosocial function. Mothers reported their own
      QoL to be comparable or higher than norms on all but one of eight sub-scales
      (energy/vitality). Compared with population norms, children with no visual
      impairment scored in the normal range for tasks measuring Verbal IQ, but below
      the mean on tasks measuring Performance IQ. According to their mothers, survivors
      of Rb have excellent school attendance and take part in most school activities.
      However, based on standardized questionnaire, they show compromised QoL. We
      consider that excellent survival rates in Rb are matched with good QoL according
      to mothers' report.

PMID- 15715693
TI  - Child Health Assessment at School Entry (CHASE) project: evaluation in 10 London
      primary schools.
AB  - AIMS: To assess the feasibility of implementing the Child Health Assessment at
      School Entry (CHASE) questionnaire, developed to capture the multiple dimensions
      of the health of children in their first year at school, and to evaluate data
      quality, reliability and validity. METHODS: Parents of 278 year-1 children, from
      10 primary schools in two London boroughs, received a parent questionnaire and
      school nurses completed a separate questionnaire from health and education
      records for children whose parents consented. Additional data on free school meal
      eligibility and ethnicity were obtained from the two Local Education Authorities.
      The parent questionnaire included the Strengths and Difficulties Questionnaire
      (SDQ) and four dimensions of the Child Health Questionnaire Parent Form-28 (CHQ
      PF28). RESULTS: Response rate was 61%. The association between school free school
      meals eligibility and response rate in each school approached significance (r = 
      0.62, P = 0.05). Data completeness of the parent questionnaire was high (mean
      98%). Data completeness of the school nurse questionnaire was more variable (mean
      82%). Cronbach's Alpha was greater than 0.6 for four of the five SDQ scales and
      greater than 0.7 for the two CHQ-PF28 multi-item scales. Relative to parents with
      qualifications, parents with no qualifications rated their children as having
      significantly more conduct problems, peer problems, and overall mental health
      problems (P < 0.01) as assessed by the SDQ, and significantly lower global health
      (P < 0.01) as assessed by the CHQ-PF28. Children with special educational needs
      and children with long-standing illness or disability were rated as having
      significantly lower global health (P < 0.05) than children without these. Sample
      tables of inter-school and inter-borough comparison of key findings demonstrate
      considerable differences in physical and mental health status. DISCUSSION: The
      questionnaire was acceptable to parents and school nurses, and feasible to
      implement within existing school resources. Initial tests of internal reliability
      and validity are satisfactory. These data have the potential to inform
      interventions and service provision at school and borough level, and public
      health trends over time.

PMID- 15715694
TI  - Do 'clumsy' children have visual recognition problems?
AB  - OBJECTIVE: Visual recognition by 8-year-old children with hand-eye co-ordination
      problems (HECP), and by a control group of children without such problems was
      tested using a task of visual closure. DESIGN: The task required the children to
      identify common objects from an incomplete visual presentation. RESULT: As
      predicted, it was found that the HECP children, who were designated as such
      solely on the basis of their motor difficulties, identified significantly fewer
      correct objects than their control counterparts. CONCLUSIONS: This finding raises
      the possibility that the visual processing problems of clumsy children contribute
      to, or even strongly determine, not only their movement problems but also their
      learning difficulties.

PMID- 15715695
TI  - Overweight children in Beirut: prevalence estimates and characteristics.
AB  - OBJECTIVE: To estimate, for the first time, overweight prevalence and associated
      characteristics in a representative sample of prepubertal children in Beirut,
      Lebanon's capital. DESIGN: A cross-sectional study with a home interview
      including measurements of weight and height and a structured questionnaire.
      SUBJECTS: A total of 234 children aged 6-8 years in Beirut: 131 boys, 103 girls.
      METHODS: Prevalence of overweight and obesity was based on the international cut
      off points for body mass index (BMI) by age and gender proposed by the
      International Obesity Task Force. The characteristics of overweight examined
      were: age, gender, household and family size, single- vs. two-parent family,
      parents' level of education and profession, physical activity and dietary intake
      of children. RESULTS: Prevalence of overweight and obesity was 26% and 7%
      respectively in boys, 25% and 6% in girls. Overweight was significantly
      associated with low physical activity (P < 0.05) and mother's BMI (P < 0.05).
      CONCLUSIONS: This study identified a high proportion of overweight in 6- to 8
      year-old children in Beirut. Reduced physical activity was the most significant
      factor associated with childhood overweight. Further studies in different regions
      in Lebanon are necessary to identify national characteristics; prevention efforts
      will be designed accordingly.

PMID- 15715696
TI  - How do carers of disabled children cope? The Ugandan perspective.
AB  - BACKGROUND: Community-based rehabilitation (CBR) was recommended by the World
      Health Organization in 1989 as the strategy for improving the quality of life of
      disabled people and their families, which should be built on local knowledge and
      practices. In Uganda, there is no documentation on how services relate to local
      knowledge. There is a need for increased knowledge and understanding of how
      family members cope with their disabled children to provide the basis for future
      service development. METHODS: A qualitative phenomenological design was used to
      develop an in-depth understanding of how Ugandan families cope with their
      disabled children in their own communities. Data were collected from 52 families
      with children with disabilities from five impairment groups, through interviews
      and observations in three districts of Uganda, one urban, two rural. RESULTS:
      There are many children with disabilities who are included, loved and cared for
      by their families. A lot of time and money is spent on seeking a cure. The
      extended family systems are breaking down and the main burden of caring for a
      disabled family member generally falls on one, sometimes two, female carers. Male
      members act as gatekeepers, controlling the key decisions concerning the child
      and the associated resources. CONCLUSIONS: CBR should move the focus of their
      services away from the disabled individual towards the whole family. It is
      important to provide accurate information about causes and prevention of
      impairments, the realities of a cure, support and respite for the female carers,
      and opportunities for the involvement of fathers. This methodology is a practical
      mechanism for collecting data that have the potential to positively influence and
      guide the development of CBR practice in the locality. At a conceptual level the
      data support the philosophy of inclusion, social integration, the importance of
      trust and respect, and utilizing a holistic approach. These are eminently
      transferable to other settings.

PMID- 15715697
TI  - Quality of child health services in primary health care facilities in south-east
      Nigeria.
AB  - BACKGROUND: To assess the quality of child health services in primary health care
      (PHC) facilities in Calabar, south-east Nigeria. DESIGN: Cross-sectional,
      descriptive design. METHODS: Key informant interviews, structured observation,
      self-administered questionnaire and focus group discussion. SETTING: Calabar,
      south-east Nigeria. Participants All 10 PHC facilities in Calabar, 252 PHC
      workers serving in the facilities, and 76 mothers whose children received care in
      the facilities. OUTCOME MEASURES: Adequacy of structure (equipment and
      personnel); process (diagnosis, training and knowledge, use of national case
      management algorithm, and supervision), and output (clients' satisfaction). MAIN
      RESULTS: PHC facilities were adequately equipped to the extent of providing
      immunization services and management of diarrhoea but not for other aspects of
      care expected of a PHC centre, including management of acute respiratory
      infections (ARI), a common problem in children in the region. Supply of essential
      drugs was inadequate in all centres and facilities for emergency care were
      lacking. Many of the health care workers (68.3%) had adequate training in
      immunization, and their knowledge scores on immunization issues (62%) was higher
      than in other aspect of PHC. Use of the national case management algorithm was
      low among PHC workers. Results of the focus group discussions with mothers showed
      that a few perceived quality of care to be poor. The main concerns were long
      waiting time, lack of essential drugs, and attitude of the health workers.
      CONCLUSIONS: Inadequacy in the quality of child health services in PHC facilities
      is a product of failures in a range of quality measures -- structural (lack of
      equipment and essential drugs), process failings (non-use of the national case
      management algorithm and lack of a protocol of systematic supervision of health
      workers). Efforts to improve the quality of child health services provided by PHC
      workers in the study setting and similar locales in less developed countries
      should focus not only on resource-intensive structural improvements, but also on
      cheap, cost-effective measures that address actual delivery of services
      (process), especially the proper use of national guidelines for case management,
      and meaningful supervision.

PMID- 15715698
TI  - How do Turkish mothers discipline children? An analysis from a behavioural
      perspective.
AB  - A descriptive study was conducted to assess the disciplinary practices of Turkish
      mothers for increasing appropriate and decreasing inappropriate behaviours of
      their children. The participants were 50 mothers of 4- to 6-year-old children
      receiving preschool education. The data were collected via a questionnaire
      consisting of open-ended questions. The results revealed that the most frequently
      used disciplinary technique for strengthening desirable behaviours of children
      was presenting verbal praise, followed by presenting activity, edible, and social
      reinforcers whereas the favourite disciplinary technique for overcoming behaviour
      problems was providing verbal explanations. These findings show that the
      participants seem to be benefiting from a variety of behavioural techniques for
      supporting their children's appropriate behaviours. However, they look less
      competent when it comes to discouraging inappropriate behaviours. These findings
      are expected to (a) offer an alternative data collection model for assessing
      parental disciplinary practices, and (b) contribute to designing parent training
      and family-focused early intervention programmes.

PMID- 15715699
TI  - A 2-year follow-up of orphans' competence, socioemotional problems and post
      traumatic stress symptoms in traditional foster care and orphanages in Iraqi
      Kurdistan.
AB  - BACKGROUND: This paper aims to compare orphans' development in two different care
      systems. METHODS: Based on age, sex, psychological trauma scores, competence and
      psychological problem scores, two comparable samples were found representing
      orphans in the traditional foster care (n = 94) and the orphanages (n = 48) in a
      middle-large city in Iraqi Kurdistan. At an index interview, Child Behaviour
      Checklist (CBCL), Harvard-Uppsala Trauma Questionnaire for Children and Post
      traumatic Stress Symptoms for Children (PTSS-C) were administered to the
      caregivers. After 1 year the CBCL, and after 2 years both the CBCL and the PTSS
      C, were-re-administered, consecutively. RESULTS: Although both samples revealed
      significant decrease in the means of total competence and problem scores over
      time, the improvement in activity scale, externalizing problem scores and post
      traumatic stress disorder-related symptoms proved to be more significant in the
      foster care than in the orphanages. While the activity scale improved in the
      foster care, the school competence deteriorated in both samples, particularly
      among the girls in the orphanages. The improvement of boys' activity scores in
      the foster care, and deterioration of girls' school competence in the orphanages
      were the most significant gender differences between samples over time.
      CONCLUSIONS: Even if the two orphan care systems showed more similarities than
      differences, the foster care revealed better outcomes over time. The results are
      discussed in relation to gender, age, socio-economic situation, cultural values
      and the characteristics of each care system.

PMID- 15715700
TI  - Child health care centres: an academic model for comprehensive child health care
      in the community.
AB  - The challenge of the discipline of paediatrics in the 21st century is to promote
      health and development of children in a way that will enable them to maximize
      their biological and social potential. The community child health centre (CHC) in
      Israel is a model of community health care service built to provide comprehensive
      health care to children and adolescents, as well as an academic setting for under
      and postgraduate paediatric training. Today there are 34 CHCs in Israel, serving
      a population of 220 000 children from birth to 18 years of age. The CHC combines
      the advantages of group practice with those of an academic medical centre and
      enables flexibility and mutual learning. Further expansion and development are
      required to realize the CHC's mission of a true comprehensive academic centre for
      paediatric community health.

PMID- 15715701
TI  - Children's perceptions of attending a residential weight-loss camp in the UK.
AB  - BACKGROUND AND AIM: Residential camps have been used to deliver weight-loss
      interventions to paediatric populations, but very little is known about how
      children perceive and evaluate attending such camps. Therefore, this study
      examined children's perceptions of attending a residential paediatric weight-loss
      camp. METHODS: Fifteen attendees (mean age = 13.56) of the 2002 Carnegie
      International Camp-UK (CIC-UK) were engaged in semi-structured interviews, which
      were transcribed verbatim and subjected to an inductive analysis procedure.
      RESULTS: Results reflected pre-camp issues including worries (boot camp fears,
      being bullied) and goals and aspirations (weight loss goals, reducing bullying,
      increasing self-esteem and making friends). Negative elements pertaining to the
      camp experience were homesickness and dietary concerns. Positive elements of the
      camp experience were enjoyment, peer support, staff support and choice of
      activities. CONCLUSION: Enjoyment, support from peers and staff and choice over
      activities appear to be important aspects in the delivery of residential obesity
      treatments for children.

PMID- 15715702
TI  - The role of parental presence in the context of children's medical procedures: a
      systematic review.
AB  - BACKGROUND: There are conflicting views and practices regarding whether or not
      parents should be present at the time of their child's medical procedure. A
      systematic review was conducted to assess the effects of parental presence in the
      paediatric treatment room on child, parent and health professional outcomes and
      to synthesize this body of literature. METHODS: Based on a comprehensive
      literature search, studies investigating parental presence in the paediatric
      treatment room were included in the review if they had a concurrent control group
      (i.e. a parent-absent group). RESULTS: A total of 28 studies met inclusion
      criteria, which included 1256 children with a parent present and 1025 children
      without a parent present. There were mixed findings regarding the effect of
      parental presence on measures of child distress and affect, however, studies of
      lower levels of evidence were more likely to report significant results. Parents
      who were present during their child's medical intervention were either better off
      or no different from parents who were absent with regard to their levels of
      distress and satisfaction. There was no evidence of increased technical
      complications nor elevated staff anxiety for health professionals attending to
      children with a parent present as compared to attending to children without their
      parents. DISCUSSION: Although parental presence may not have a clear, direct
      influence on child distress and behavioural outcomes, there are potential
      advantages for parents. It seems appropriate that clinicians provide parents with
      the opportunity to be present during their child's painful procedure.

PMID- 15715712
TI  - Bartonellosis: light and shadows in diagnostic and therapeutic issues.
AB  - Cat-scratch disease involves a prolonged and/or complicated course, and lymph
      node drainage is usually required. Culture and molecular techniques often yield
      negative results, but immunofluorescence assays may give early information, and
      elevated antibodies may persist for months. Cat-scratch disease should be
      suspected in patients with prominent swelling of lymph nodes draining from the
      upper limbs, limited systemic involvement, and typical epidemiological-clinical
      features. The temporal antibody response during the sub-acute course remains
      unknown. Although biomolecular assays are available, the time between onset and
      investigation is an obstacle to positive results. The role of surgical
      debridement and the unpredictable activity of antimicrobial agents warrant
      further investigation.

PMID- 15715713
TI  - Recent trends in molecular diagnostics for Toxoplasma gondii infections.
AB  - Toxoplasmosis is an important parasitic infection of man and animals. It is well
      known that the progression and severity of disease depend on the immunological
      status of the host, but recent studies suggest that the genetics of the parasite
      can also play a role. Diagnosis based on clinical appearance and serology is not
      always easy. However, molecular methods do not depend on an immune response, and
      allow direct detection of the parasite in biological samples. Thus they can be
      used to establish a diagnosis when serological tests are not definitive.
      Multicopy sequences specific for Toxoplasma gondii, e.g., the B1 gene or the 529
      bp sequence, are especially useful in molecular tests. Real-time PCR is very
      sensitive and is a promising technique that is capable of providing a
      quantitative result. Molecular methods are also used for genotypic
      characterisation of T. gondii isolates. Analysis of polymorphic sequences
      determines the precise strain. The choice of sequence is critical when
      undertaking studies on the correlation between clinical signs and symptoms of
      disease and the T. gondii genotype. Further studies involving direct genotyping
      of T. gondii from clinical samples are needed.

PMID- 15715715
TI  - Integrons and gene cassettes in clinical isolates of co-trimoxazole-resistant
      Gram-negative bacteria.
AB  - Despite a trend of declining consumption, resistance to co-trimoxazole has
      increased during a 12-year period in Stockholm. The molecular background to this
      surprising development was investigated by using PCR to screen for integrons and
      specific resistance genes, followed by sequence analysis of selected integrons,
      in 105 clinical urinary isolates of Gram-negative bacteria selected partly for
      trimethoprim resistance. Sixty-five integrons of class 1 or 2 were detected in a
      subset of 59 isolates, and of these positive isolates, all but one were resistant
      to trimethoprim. However, 11 isolates were resistant to trimethoprim, but
      negative for integrons. Isolates positive for integrons were resistant to an
      average of 4.2 antibiotics, compared with 1.9 antibiotics for integron-negative
      isolates. Despite this, the only gene cassettes identified in 19 class 1
      integrons analysed were dfr and aadA cassettes. Thus, only resistance to
      trimethoprim, streptomycin, spectinomycin and sulphonamides could be explained by
      the presence of integrons in these isolates. A new dfr gene, named dfrA22, was
      discovered as a single gene cassette in a class 1 integron. In addition,
      sulphonamide resistance in many isolates was caused by carriage of sul2, which
      has no known association with integrons. Resistance to co-trimoxazole and many
      other antibiotics was thus not accounted for fully by the presence of integrons
      in these isolates.

PMID- 15715714
TI  - Identification of coagulase-negative staphylococci other than Staphylococcus
      epidermidis by automated ribotyping.
AB  - As routine identification of coagulase-negative staphylococci is problematic, the
      performance of automated ribotyping was evaluated for identification of coagulase
      negative staphylococci other than Staphylococcus epidermidis. In total, 177
      isolates were tested, comprising 149 isolates from blood samples, 15 isolates
      that were not identified by internal transcribed spacer (ITS)-PCR in a previous
      study, and 13 reference strains. The identification results were compared with
      those obtained by the API 20 Staph system, with standard phenotypic and molecular
      methods as reference. Most (n = 166; 93.8%) isolates were identified correctly by
      automated ribotyping. For 61 isolates, API 20 Staph and ribotyping were in
      agreement, but for 105 isolates, ribotyping provided correct identification and
      API 20 Staph did not. Four isolates not identified by automated ribotyping were
      recognised correctly by API 20 Staph. The remaining seven isolates could not be
      identified by either of the two methods. Automated ribotyping was able to
      distinguish Staphylococcus capitis reliably from Staphylococcus caprae. The
      results demonstrate the value of automated ribotyping for identification of
      coagulase-negative Staphylococcus (CoNS) isolates from human sources and may help
      to clarify the clinical relevance of CoNS species. In addition, automated
      ribotyping was able to detect polymorphisms that may be useful for
      epidemiological purposes within S. capitis, Staphylococcus hominis,
      Staphylococcus haemolyticus, Staphylococcus simulans, S. caprae, Staphylococcus
      warneri, Staphylococcus lugdunensis, Staphylococcus schleiferi, Staphylococcus
      sciuri, Staphylococcus pasteuri and Staphylococcus xylosus.

PMID- 15715716
TI  - PER-1- and OXA-10-like beta-lactamases in ceftazidime-resistant Pseudomonas
      aeruginosa isolates from intensive care unit patients in Istanbul, Turkey.
AB  - The presence of PER-1- and OXA-10-like beta-lactamases was investigated by PCR in
      49 ceftazidime-resistant Pseudomonas aeruginosa isolates from patients
      hospitalised in the 24-bed general intensive care unit of the Istanbul Faculty of
      Medicine during a 12-month period between February 1999 and February 2000. The
      clonal relatedness of the isolates was investigated by random amplified
      polymorphic DNA (RAPD) analysis, and the sequences of the PER-1 and OXA genes
      from all isolates were determined. The rates of resistance of the isolates to
      imipenem, aztreonam and cefepime were 98%, 92% and 96%, respectively, and to
      piperacillin and piperacillin-tazobactam were 41% and 37%, respectively. Using
      the double-disk synergy test, 37% (18/49) of the isolates were identified as
      extended-spectrum beta-lactamase producers. The PER-1 gene was identified in 86%
      (42/49) and the OXA-10 gene in 55% (27/49) of the ceftazidime-resistant isolates.
      Of isolates carrying the PER-1 gene, 48% (20/42) also carried the OXA-10 gene.
      The respective nucleotide sequences were identical for each isolate. Sixteen RAPD
      patterns were detected among the PER-1-positive isolates, but 60% (25/42) of the
      PER-1-positive isolates belonged to two distinct patterns, while the remainder
      exhibited a wide clonal diversity. The results indicated that the prevalence of
      PER-1- and OXA-10-like beta-lactamases remains high among ceftazidime-resistant
      P. aeruginosa isolates in Turkey.

PMID- 15715717
TI  - Antibiotic resistance of Escherichia coli from community-acquired urinary tract
      infections in relation to demographic and clinical data.
AB  - This prospective study determined the antibiotic susceptibility of 164 isolates
      of Escherichia coli from the urine of 164 patients (112 female, 52 male; mean age
      of 54.12 years) with community-acquired urinary tract infection (UTI). Half of
      the isolates were from uncomplicated UTI and half from complicated UTI (52 males
      and 34 females). Overall, 57.3% of isolates were resistant to ampicillin, 25% to
      co-trimoxazole, 20.1% to nalidixic acid, 14% to norfloxacin and ciprofloxacin,
      and 0% to fosfomycin and nitrofurantoin. Of the 82 isolates from complicated UTI,
      16 (19.5%) were resistant to norfloxacin and ciprofloxacin, compared with seven
      (8.5%) from uncomplicated UTI (p 0.043). Isolates from patients aged >50 years
      were significantly more resistant than those from patients aged <50 years for
      nalidixic acid (p 0.007) and the fluoroquinolones tested (p 0.015). Resistance to
      fluoroquinolones was 25% (13/52) in males and 9% (10/112) in females (p 0.006).
      For patients with and without previous antimicrobial therapy, there was a
      significant difference only for resistance to nalidixic acid (p < 0.001) and the
      fluoroquinolones (p 0.011). There were adequate susceptibility rates to
      fosfomycin, nitrofurantoin and the fluoroquinolones for empirical use in the
      treatment of acute uncomplicated UTI. In order to interpret cumulative
      susceptibility data from the primary healthcare setting, it is necessary to take
      into account the type of UTI (uncomplicated vs. complicated), previous
      antimicrobial therapy, and the sex and age of each patient.

PMID- 15715718
TI  - European surveillance study on the antibiotic susceptibility of Propionibacterium
      acnes.
AB  - Propionibacterium acnes strains are recovered from infections linked to surgical
      procedures, foreign bodies and septicaemia. This study investigated the
      antibiotic susceptibility patterns of P. acnes isolates from different systemic
      infections and determined the genomic diversity among resistant P. acnes isolates
      with low-frequency restriction analysis of chromosomal DNA by pulsed-field gel
      electrophoresis (PFGE). In total, 304 P. acnes isolates from 13 laboratories in
      13 European countries were tested against six antimicrobial agents by the NCCLS
      reference agar dilution method and the breakpoints recommended by the European
      Committee on Antimicrobial Susceptibility Testing. Blood isolates were
      encountered most frequently, followed by those from skin and soft tissue
      infections, and abdominal infections. Of the isolates examined, 2.6% were
      resistant to tetracycline, 15.1% to clindamycin, and 17.1% to erythromycin. No
      resistance was observed to linezolid, benzylpenicillin or vancomycin. There was
      considerable variation between countries in the proportion of resistant strains,
      ranging from 83% in Croatia and 60% in Italy to 0% in The Netherlands. Isolates
      from blood were predominant among the resistant isolates. Seventeen clones and 78
      banding patterns were identified among the resistant isolates. It was concluded
      that antimicrobial resistance has now emerged among P. acnes isolates from
      systemic infections.

PMID- 15715719
TI  - Low prevalence of methicillin-resistant Staphylococcus aureus with reduced
      susceptibility to glycopeptides in Belgian hospitals.
AB  - Staphylococcus aureus strains with decreased susceptibility to glycopeptides
      (GISA) have been associated with increased risk of glycopeptide treatment
      failure. To assess the prevalence of these strains in hospitalised patients in
      Belgium, 455 methicillin-resistant S. aureus (MRSA) isolates collected in 2001
      were screened by two assays: (i) growth on vancomycin agar screen (VAS; brain
      heart infusion agar (BHI) + vancomycin 6 mg/L); and (ii) a synergy/antagonism
      test with aztreonam/cefazolin on Mu3 agar (BHI + vancomycin 3 mg/mL). Isolates
      growing on VAS or Mu3 agar were characterised further by analysis of population
      susceptibility profiles. MICs of glycopeptides were determined by agar dilution,
      broth microdilution and Etest (low and high inocula) methods. The isolates were
      genotyped by pulsed-field gel electrophoresis (PFGE) and determination of
      staphylococcal cassette chromosome mec (SCCmec) type. No GISA isolates were
      found. Three (0.7%) hetero-vancomycin intermediate S. aureus (hVISA) and ten
      (2.2%) hetero-teicoplanin intermediate S. aureus (hTISA) isolates were identified
      by population analysis. All but one hetero-GISA isolate belonged to either
      epidemic PFGE group A/SCCmec type I (69%) or PFGE group D/SCCmec type I (23%),
      both of which were resistant to gentamicin. The sensitivity and specificity for
      the detection of hetero-GISA by the two assays were 15.4% and 99.8%,
      respectively, for VAS, and 84.6% and 95.9%, respectively, for Mu3. The data
      indicated that hetero-GISA strains were uncommon among Belgian MRSA isolates from
      hospitalised patients. Use of Mu3 agar was more sensitive, but less specific,
      than VAS as a screening method.

PMID- 15715720
TI  - Rose Bengal test: diagnostic yield and use for the rapid diagnosis of human
      brucellosis in emergency departments in endemic areas.
AB  - The aim of the present study was to analyse the diagnostic yield of the rose
      Bengal test for the rapid diagnosis of human brucellosis in an emergency
      department in an area where the disease is endemic. The study included 711
      patients diagnosed initially with brucellosis and 270 controls. Brucellosis
      patients were divided into three groups: group I, individuals with no regular
      exposure to or history of brucellosis; group II, individuals exposed repeatedly
      to Brucella infection; and group III, individuals infected with Brucella who had
      received appropriate treatment during the previous 12 months. Blood cultures were
      positive for 445 (62.6%) brucellosis patients, while the remaining 266 (37.4%)
      patients were diagnosed according to clinical and serological criteria. The
      overall sensitivity of the rose Bengal test was 92.9%. The specificities for
      groups I, II and III were 94.3%, 91.7% and 76.9%, respectively, with positive
      likelihood ratios of 16.5, 10.4 and 4.2, respectively. The diagnostic gain after
      the performance of the rose Bengal test was good or very good in patients with no
      previous exposure to Brucella or history of brucellosis, but poor in patients who
      were exposed repeatedly to Brucella or had a history of brucellosis and a low pre
      test probability. Use of the rose Bengal test as the sole technique for the
      diagnosis of brucellosis in endemic areas should be considered very carefully in
      the context of patients who are exposed repeatedly to Brucella or have a history
      of brucellosis.

PMID- 15715721
TI  - Long-term surveillance of invasive group A streptococcal disease in The
      Netherlands, 1994-2003.
AB  - A nationwide laboratory-based surveillance study of invasive group A
      streptococcal (GAS) infections was conducted in The Netherlands from May 1994
      until December 2003 (average population during this period was 15 729 704).
      Microbiologically invasive isolates were obtained from 1504 patients, with most
      (70%) isolates cultured from blood. There was a clear seasonal pattern in
      invasive streptococcal infections, with an estimated annual incidence that peaked
      in 1996 (4.0 cases/100 000 individuals/year) and was at its lowest in 1999 (2.0
      cases/100 000 individuals/year). Twenty-eight different M-types were identified,
      of which the most frequent were M1 (339/1504, 23%), M3 (187/1504, 12%), M89
      (174/1504, 12%), M28 (164/1504, 11%), M12 (109/1504, 7%) and M6 (55/1504, 4%).
      There was a high degree of variation in the relative annual contributions of the
      predominant M-types, but variations in M1 and M3 combined correlated with overall
      changes in the annual incidence. The contribution of the patient group aged > or
      = 56 years to all cases of invasive GAS disease increased during the study
      period, whereas that of the group aged 0-20 years decreased. A peak in the
      incidence of invasive GAS disease among the patient group aged 30-34 years did
      not vary during the study period, indicating that the high incidence of invasive
      GAS disease in this age group was age-specific rather than cohort-related.

PMID- 15715722
TI  - First cluster of vancomycin-resistant Enterococcus faecalis isolates in Cyprus.
AB  - This report describes the first patient in Cyprus to be infected with a
      vancomycin-resistant enterococcus, as well as the microbiological characteristics
      of a cluster of vancomycin-resistant enterococcus isolates from the intensive
      care unit where the index case was hospitalised. All isolates were identified as
      Enterococcus faecalis, belonged to the same clone, and contained the vanA gene
      cluster. Transfer of glycopeptide resistance to a susceptible strain of E.
      faecalis could not be detected.

PMID- 15715723
TI  - Antimicrobial susceptibility patterns of clinical isolates of Staphylococcus
      aureus in Nepal.
AB  - Isolates of Staphylococcus aureus (n = 117) from patients attending a tertiary
      care centre in western Nepal were tested for susceptibility to penicillin,
      oxacillin, gentamicin, erythromycin and ciprofloxacin. Eighteen (15.4%) were
      methicillin-resistant. Susceptibility among methicillin-resistant isolates varied
      from 0% (penicillin) to 16.6% (erythromycin and gentamicin), but varied among
      methicillin-susceptible isolates from 39.4% (penicillin) to 97.0%
      (ciprofloxacin). Fourteen (77.8%) of the methicillin-resistant isolates were
      resistant to all agents tested. Implementation of an appropriate antibiotic
      policy would reduce the risk of further development of antimicrobial resistance.

PMID- 15715724
TI  - Susceptibility of Escherichia coli to the amoxycillin-clavulanate combination:
      which recommendations should be used to provide relevant information to
      clinicians?
AB  - This study compared MIC distributions of amoxycillin-clavulanate obtained with
      NCCLS and French (Comite de l'Antibiogramme de la Societe Francaise de
      Microbiologie; CA-SFM) methodologies for Escherichia coli isolates from urine
      that were non-susceptible to amoxycillin-clavulanate by the disk diffusion
      method. With the NCCLS and CA-SFM methods, 74% and 13%, respectively, of these
      isolates were susceptible to amoxycillin-clavulanate. Therefore, the apparent
      relatively poor efficacy of amoxycillin-clavulanate against E. coli in French
      hospitals probably reflects a methodological difference rather than a localised
      resistance problem. This implies that amoxycillin-clavulanate could be used as an
      alternative to fluoroquinolones for treatment of E. coli urinary tract
      infections. Susceptibility tests for amoxycillin-clavulanate should be
      standardised worldwide.

PMID- 15715725
TI  - Chlamydia trachomatis infections in heterosexuals attending sexually transmitted
      disease clinics in Slovenia.
AB  - This study assessed the age and gender distribution of Chlamydia trachomatis
      infections among patients attending two clinics for sexually transmitted diseases
      (STDs) in Slovenia. Between January 1999 and December 2003, 1714 heterosexual
      male and 892 heterosexual female patients were tested for C. trachomatis. The
      prevalence of C. trachomatis infection was 19.5% (n = 334) for male patients and
      10.7% (n = 96) for female patients, with the highest prevalence in the group aged
      15-30 years. The prevalence decreased between 2000 and 2003 among female
      patients. The results support the implementation of routine screening for C.
      trachomatis genital infection among male and female patients aged < 30 years
      attending STD clinics in Slovenia.

PMID- 15715726
TI  - Development of a novel assay method for colistin sulphomethate.
AB  - Increased use of colistin therapy for infections caused by Pseudomonas aeruginosa
      has indicated a need for a more robust microbiological assay technique. This
      report describes a quick and simple microbiological assay for quantifying levels
      of colistin sulphomethate in serum and urine samples from cystic fibrosis
      patients. The technique uses no specialised or costly equipment and is suitable
      for use in all routine diagnostic microbiology laboratories.

PMID- 15715727
TI  - Comparison of three differential media for the presumptive identification of
      yeasts.
AB  - This study evaluated three differential media, CHROMagar Candida, BiGGY agar and
      Albicans ID2 agar, for the presumptive identification of yeast species. In total,
      215 yeast isolates were included in the study. The sensitivity and specificity of
      CHROMagar Candida, BiGGY agar and Albicans ID2 agar for the detection of Candida
      albicans were 100% and 100%, 91% and 92.7%, and 99.2% and 92.7%, respectively.
      CHROMagar Candida was a reliable tool for the presumptive identification of C.
      albicans, Candida tropicalis, Candida krusei and Candida glabrata. Albicans ID2
      agar was useful for the detection of C. albicans.

PMID- 15715728
TI  - Caspofungin: a new therapeutic option for fungal endocarditis.

PMID- 15715729
TI  - The causal agents of 'entomophthoramycosis' belong to two different orders: a
      suggestion for modification of the clinical nomenclature.

PMID- 15715732
TI  - Professionally indicated short-term risk-taking in the treatment of borderline
      personality disorder.
AB  - OBJECTIVE: To define and explore the rationale for professionally indicated short
      term risk-taking in treating adults with borderline personality disorder, and
      discuss prerequisites for the approach, clinical implementation and medicolegal
      contexts. CONCLUSION: When prerequisites are met and clinical and medicolegal
      practice is sound and thorough, taking short-term risk, as part of a
      comprehensive treatment, is a legitimate professional consideration in working
      with some adults with borderline personality disorder.

PMID- 15715731
TI  - Hidden truths: the politics of brain, mind and soul in Australian psychiatry.

PMID- 15715733
TI  - Medical practitioners and their families as patients.
AB  - OBJECTIVE: To explore diagnoses, treatment methods, compliance and outcome in a
      cohort of medical practitioners and their families seen in a private practice
      setting to identify characteristics of this group. METHODS: A systematic
      retrospective case-note review was conducted of all medical practitioners, their
      partners and children seen in a private practice setting over 15 years,
      documenting mode of referral, diagnosis, attendances, mode of treatment, and
      outcome. RESULTS: Seventy-seven medical families were identified, including 45
      doctors, 21 partners and 11 offspring as the primary patient; 38 of the doctor
      group were self-referred. Doctors and their families were likely to accept
      treatment guidelines as recommended and to continue until a joint decision was
      made to terminate. CONCLUSIONS: Doctors presenting themselves for treatment in a
      private practice are a highly motivated and compliant group, who make significant
      changes in therapy. They defy directly the usual findings on "impaired
      physicians" who may be a different group, the latter generally being referred for
      psychiatric treatment as "impaired physicians" through statutory bodies such as
      medical boards. With increasing de-stigmatization and increasing education on the
      benefits of self-care, doctors may be seeking appropriate early intervention.

PMID- 15715734
TI  - Obesity in schizophrenia: what can be done about it?
AB  - OBJECTIVE: To selectively review the literature on obesity in people with
      schizophrenia. CONCLUSIONS: Obesity is a common problem for people with
      schizophrenia, with an estimated 40-60% of this population being obese or
      overweight. Obesity among the mentally ill may contribute to adverse medical and
      psychological consequences as well as medication non-compliance and poorer
      quality and enjoyment of life. This review discusses the issues related to
      obesity in schizophrenia and the role of pharmacological and behavioural
      treatments in the reduction of obesity and maintenance of gains.

PMID- 15715735
TI  - How well do Australian medical schools prepare general practitioners to care for
      patients with mental disorders?
AB  - OBJECTIVE: The purpose of the present paper was to map the mental health
      workloads of general practitioners (GPs) , and to determine GPs' views of the
      adequacy of their undergraduate training in psychiatry. METHODS: Twenty-nine GPs
      who had graduated since 1980 from an Australian medical school provided data on
      339 consecutive adult patients with conspicuous psychological disorders. After
      listing their patients' problems and management plans, doctors rated the value of
      their undergraduate teaching in preparing them for this task. RESULTS:
      Depression, anxiety and substance abuse accounted for 71% of reported cases.
      Virtually all patients were given some psychologically orientated treatment. Only
      half were prescribed a psychotropic medication. Nineteen of the 29 doctors wished
      that they had received more training in counselling. CONCLUSIONS: In an earlier
      survey it was found that Australian and New Zealand medical school curricula
      focused largely on the diagnosis and pharmacological management of psychosis and
      depression. The GPs in the present study most commonly applied psychologically
      orientated treatments of anxiety, depression and substance abuse. It is proposed
      that medical schools provide tuition to medical students in counselling.

PMID- 15715736
TI  - The patient's voice in a problem-based learning case.
AB  - OBJECTIVE: Problem-based learning (PBL) relies upon trigger material, often a
      paper case, to stimulate self-directed enquiry and group discussion. We describe
      the process of writing a PBL case based upon a patient's narrative account of her
      experiences of psychiatric illness, and the possible benefits of that
      collaboration for the patient, as well as for student learning. CONCLUSION: Real
      patients are under-utilized in teaching, as are their narratives, and both are
      believed to be resources worthy of further attention.

PMID- 15715737
TI  - Identifying marginal housing for people with a mental illness living in rural and
      regional areas.
AB  - OBJECTIVE: Homelessness among people with a mental illness is a serious issue.
      The purpose of the present study was to identify the types of housing available
      for people with a mental illness in the region, to develop an audit tool to
      assess the housing of patients of the mental health service, and to pilot this
      audit tool. METHODS: Key informants were interviewed to obtain information about
      the type of housing options available in the Loddon Campaspe Southern Mallee
      Region, Victoria, Australia. This information was used to develop a survey to
      audit the housing status of existing patients of the area mental health service.
      A pilot study using the survey was completed by case managers for 81 patients who
      were being case managed by the area mental health service. RESULTS: There was a
      wide variety of housing options in the region but housing availability was not
      evenly distributed. Although most patients lived in owned or rented
      accommodation, a substantial proportion of patients had difficulties with
      accessing the required services, the affordability of their housing, uncertainty
      of tenure or were at risk of violence within their housing. CONCLUSIONS: A
      substantial proportion of patients treated by a rural area mental health service
      had lived in impoverished housing.

PMID- 15715738
TI  - Rural Integrated Primary Care Psychiatry Programme: a systems approach to
      education, training and service integration.
AB  - OBJECTIVE: To describe the development of a rural primary care psychiatry
      programme, within a stepped collaborative care model. CONCLUSION: Development of
      a system-wide approach to the provision of mental health services offers the
      opportunity to increase the proportion of people with mental health problems who
      receive effective treatment. In addition, it enables allocation of resources and
      matching of interventions to patient preference and clinical need. This is
      particularly important in rural areas where there is a shortage of specialist
      mental health services and practitioners.

PMID- 15715739
TI  - Consumer and service determinants of completion of a consumer self-rating outcome
      measure.
AB  - OBJECTIVE: To study the relative contribution of consumer, clinician and service
      factors to whether or not consumers completed a self-rating measure in the
      context of routine outcome measurement. METHODS: Four Victorian mental health
      services commenced routine outcome measurement in their adult services in mid
      2000. Clinician-completed measures (Health of the Nation Outcome Scales (HoNOS)
      and Life Skills Profile (LSP)) and a consumer self-rated measure (Behaviour and
      Symptom Identification Scale (BASIS)) were entered into specialized software.
      Analyses were restricted to assessments conducted at review in the community.
      RESULTS: Wide differences were observed between the four agencies in the rates of
      completion of the self-rating measure. Overall, consumer characteristics
      associated with greater likelihood of completion were lower age, non-organic
      diagnosis, lesser severity as measured by the HoNOS, and lesser disability as
      measured by the LSP. A more focused analysis showed that agency, lower age, and
      higher compliance were most reliably associated with completion. Significant
      proportions of clinicians had no recorded instances of consumer self-rating
      associated with their assessments. CONCLUSIONS: Service and clinician factors
      appear to be equally important as consumer factors in whether or not a self
      rating measure was completed. Information systems designed for outcomes
      measurement should include indications of whether or not a self-rating was
      invited, and, if not, why not. The results suggest that consumer self-rating is
      not yet firmly established in the outcomes measurement culture.

PMID- 15715740
TI  - Privacy and identity in a changing world.
AB  - OBJECTIVE: To consider the issues of privacy and identity relevant to psychiatric
      practice in the context of recent technological initiatives and the society that
      has produced them. CONCLUSIONS: Emerging technologies may have implications for
      the ways in which Western society relates. These are likely to affect the ways
      patients present, their concerns and how we may best assist them. Psychiatry may
      also be of benefit in the evaluation of the privacy implications of new
      technologies.

PMID- 15715741
TI  - Job satisfaction and burnout in mental health services for older people.
AB  - OBJECTIVE: The objective of the present paper was to identify factors associated
      with job satisfaction and burnout among staff working in mental health services
      for older people. METHODS: A postal survey was distributed to staff members from
      eight mental health services for older people in Western Australia. Staff focus
      groups identified causes of work stress. RESULTS: The response rate was 33%
      (116/349). Teamwork, social support and clear roles had a positive effect on job
      satisfaction. Community staff members had higher job satisfaction than ward
      staff. Nurses reported higher burnout and lower job satisfaction than other
      mental health professionals. Staff members working in newer models of service
      delivery had higher job satisfaction than those working in more traditional
      models. CONCLUSION: Surveys and focus groups were an effective means of
      identifying factors associated with job satisfaction in mental health staff
      members. Newer models of service delivery with team building and supportive
      management may improve the workplace for staff.

PMID- 15715742
TI  - O Anna: being Bertha Pappenheim--historiography and biography.
AB  - OBJECTIVE: To review the famous case of Anna O. (the index case of
      psychoanalysis) as seen by each generation, in the light of current knowledge and
      thinking. CONCLUSIONS: The case was neither a catharsis nor a cure as described.
      Historical research has revealed a significantly different outcome, shedding new
      light on the motives of the chief protagonists, Breuer and Freud. No less
      interesting but greatly neglected is the life of Bertha Pappenheim, the real
      identity of Anna O.

PMID- 15715743
TI  - Iatrogenic dependency disorder.
AB  - OBJECTIVE: To argue for the direct election of RANZCP officials as a means of
      ensuring that College statements and political activities correspond as closely
      as possible to the opinions and interests of the average psychiatrist.
      CONCLUSIONS: The case to abolish item 319 and restore 5 day-per-week sessions is
      out of touch with political reality. It wastes limited political capital by the
      College, or other psychiatric organizations, that would be better used for other
      purposes.

PMID- 15715745
TI  - Combined use of amisulpride and clozapine for patients with treatment-resistant
      schizophrenia.
AB  - OBJECTIVE: To report on a trial of adding amisulpride to clozapine. METHODS:
      Description of six cases. RESULTS: Six patients who had been on clozapine were
      commenced on amisulpride. All patients had had unwanted effects with clozapine,
      particularly sedation, hypersalivation, or weight gain. Five patients reported a
      high level of satisfaction with the regimen, having a reduction in the level of
      sedation and improvement in levels of motivation and energy, without recurrence
      of positive symptoms. CONCLUSION: The combined use of amisulpride and clozapine
      would appear to be an appropriate and beneficial treatment.

PMID- 15715746
TI  - Relevance of sleep paralysis and hypnic hallucinations to psychiatry.
AB  - OBJECTIVE: To describe a patient who presented with psychopathology in the wake
      of sleep paralysis and hypnopompic hallucinations, and to discuss the importance
      of these phenomena to psychiatric diagnoses. METHODS: Case report. RESULTS: A 25
      year-old black South African woman developed paranoid beliefs and a sad and
      anxious mood in the wake of her first experience of sleep paralysis and hypnic
      hallucinations. She had no history of other sleep-related events. Reassurance,
      explanation of the physiological basis of her experience, and a short course of
      low-dose diazepam were provided. Her mood and sleep improved promptly and she no
      longer held paranoid beliefs. She did not experience further episodes of sleep
      paralysis or hypnic hallucinations and improvement was sustained at 6 months.
      CONCLUSIONS: It pays to probe for the core experiences or events that patients
      may be explaining by devising "delusions". Acute, nocturnal-onset, first-time
      psychopathology warrants inquiry for sleep paralysis and hypnic hallucinations.
      Sleep-related side-effects of psychotropic medications need to be studied more
      closely.

PMID- 15715747
TI  - Boundary violations.

PMID- 15715748
TI  - Should psychiatrists lie to access suitable treatment for their patients?

PMID- 15715749
TI  - Seduction in the forensic evaluation.

PMID- 15715750
TI  - Kraepelin, Alzheimer and Munich.

PMID- 15715751
TI  - Detention centres and the RANZP.

PMID- 15715752
TI  - 'Like Minds, Like Mine': a New Zealand project to counter the stigma and
      discrimination associated with mental illness.
AB  - OBJECTIVE: To demonstrate how mass media advertising and community education has
      been successfully used in New Zealand as part of a comprehensive public health
      project to reduce stigma and discrimination associated with mental illness.
      CONCLUSIONS: The involvement of people with experience of mental illness in the
      campaign has been critical to its success. Advertising involving the stories of
      well-known and famous people who have experienced mental illness has created
      significant interest, awareness and improved attitudes among the general public.
      Local community education and other follow-up activities have also contributed to
      this success.

PMID- 15715753
TI  - Policy, structural change and quality of psychiatric services in Australia: the
      views of psychiatrists.
AB  - OBJECTIVE: Given that 10 years have elapsed since the implementation of
      Australia's National Mental Health Strategy, the aim of the paper was to
      ascertain the views of the country's psychiatrists about changes in mental health
      services. METHODS: A survey was mailed to all Fellows of the Royal Australian and
      New Zealand College of Psychiatrists living in Australia; 1039 out of 2059 (50%)
      returned the questionnaire. RESULTS: Private care has not changed much in the
      last 5 years, but the quality in public psychiatric services has deteriorated.
      While 67% of private practitioners, 46% of psychiatrists with mixed practice, 39%
      of exclusively public psychiatrists and 27% of academics believed public practice
      had deteriorated, only 18% of psychiatrist administrators believed that to be the
      case. Daily or weekly problems admitting patients to hospital was reported by 40%
      of psychiatrists working in the public system. Public psychiatrists believed that
      they now treat more patients who are more disturbed, more acute and more
      demanding. However, they see their patients less often, provide less
      psychotherapy and use more medication. Administrative demands have increased.
      CONCLUSIONS: According to psychiatrists, implementation of the National Mental
      Health Strategy has not yet resulted in better psychiatric care in the public
      health system.

PMID- 15715754
TI  - Surveying perceptions of the progress of national mental health reform.
AB  - OBJECTIVE: To provide comment on the latest Australian government commitment to a
      5 year plan under the National Mental Health Strategy. CONCLUSIONS: In the
      absence of a credible system of accountability for the implementation of mental
      health reform, the Mental Health Council of Australia, in association with the
      Brain and Mind Research Institute, has taken up the task of auditing. A national,
      government-supported system needs to be developed in order to monitor progress of
      genuine mental health reform in Australia.

PMID- 15715755
TI  - A mental health and substance abuse service for a youth detention centre.
AB  - OBJECTIVES: To describe a new programme, the Mental Health Alcohol Tobacco and
      Other Drugs Service (MHATODS) at the Brisbane Youth Detention Centre, which aims
      to provide young people in detention with the same quality of mental health and
      substance dependency services that would normally be available to them in the
      community. CONCLUSIONS: Young people in detention suffer from considerable mental
      health and substance abuse problems. MHATODS seeks to address the specific needs
      of this group of young people. Its innovative structure recognizes the
      limitations of the prevailing paradigm of separate service delivery for mental
      health and drug and alcohol treatment, and has created an integrated treatment
      service for young people in detention.

PMID- 15715756
TI  - Commitment and collaboration for excellence in older persons' mental health: the
      ACT experience.
AB  - OBJECTIVE: To describe the development of the older persons' mental health
      service in the Australian Capital Territory (ACT), a region with both urban and
      rural characteristics. METHODS: Elements include: (i) collaboration with health
      care and non-governmental organizations; (ii) provision of consultation-liaison
      service to patients, family and professional care-providers via collaboration
      with general practitioners; (iii) partnerships built through consultation,
      regular communication, education and training of primary health-care providers;
      and (iv) development of a multidisciplinary academic centre in partnership with
      the local universities designed to enhance roles in education, training and
      research. The disciplines of general practice, nursing, psychology, social work
      and psychiatry collaborate in service provision, education and an active research
      centre. CONCLUSIONS: An expanded, multidisciplinary comprehensive service has
      been developed from an initial consultation-liaison model, illustrating that
      commitment and collaboration with existing services and carer groups can advance
      care.

PMID- 15715757
TI  - Why do doctors dislike treating people with somatoform disorder?
AB  - OBJECTIVE: To consider the question of why doctors dislike treating people with
      somatoform disorder, with a view to assisting debate and improving services.
      METHODS: The literature was examined, and compared with clinical experience.
      RESULTS: Psychological, sociological and evolutionary theory make relevant
      contributions. Important factors include that these conditions are problematic
      and positive outcomes may not be possible given current knowledge and clinical
      skills and techniques. Patients may not accept that their problem is a form of
      psychiatric or brain disorder. Most importantly, the doctor may not accept that
      somatoform disorders are beyond the control of patients, setting the scene for
      irritation and unsatisfactory interactions. CONCLUSIONS: There are many factors
      that underlie the dislike of some doctors for treating people with somatoform
      disorder. There is a pressing need for educational efforts to help students and
      doctors accept that the symptoms of somatoform disorder are beyond the control of
      those who suffer them.

PMID- 15715758
TI  - Use of a routine outcome measure in a consultation-liaison mental health service.
AB  - OBJECTIVE: The problem severity of patients seen by a psychiatric consultation-
      liaison service was studied through the use of a routine outcome measure.
      METHODS: Ratings on the Health of the Nation Outcome Scales (HoNOS) over nearly 3
      years in the emergency department, general hospital, and on admission to the
      acute psychiatric unit were compared. RESULTS: Mean HoNOS total scores in the
      emergency department were not significantly different from those at admission to
      the acute psychiatric unit, but were significantly higher than those in the
      general hospital. Mean scores in all three settings were higher than those
      obtained at case review of psychiatric patients in the community. Despite
      differences in age, sex, and psychiatric diagnosis between the three hospital
      settings, differences in mean HoNOS total scores remained substantially unchanged
      after adjustment for these factors. Most HoNOS assessments were performed by
      medical staff. CONCLUSIONS: The suspected high levels of problem severity and
      comorbidity of patients seen by a psychiatric consultation-liaison service were
      confirmed through the use of a routine outcome measure.

PMID- 15715759
TI  - Religion, spirituality and psychiatry: steps towards rapprochement.
AB  - OBJECTIVES: To consider the claim that there is a fundamental epistemological
      conflict between religion and psychiatry over what constitutes rational
      explanation, and what impediment this might be to rapprochement between the two.
      CONCLUSIONS: An epistemological gap most certainly exists, but there is a growing
      acceptance of the importance of religion and spirituality to psychiatry.
      Rapprochement may best be achieved by increasing psychiatric awareness and
      knowledge of the issues, and by a willingness to embrace intellectual, cultural
      and religious pluralism.

PMID- 15715760
TI  - Spiritually augmented cognitive behavioural therapy.
AB  - OBJECTIVE: To describe spiritually augmented cognitive behaviour therapy (SACBT)
      and its applications. METHODS: The background for the need to incorporate
      spirituality into therapy is considered, and SACBT as a therapy for sustaining
      mental health and functional recovery is described. Cognitive and behavioural
      components are considered, including the use of existential techniques in
      discovering meaning. The use of meditation and the validation and incorporation
      of the appropriate belief system of patients into their treatment are described.
      RESULTS: Controlled studies have demonstrated 16-session SACBT to be beneficial
      in extinguishing hopelessness and despair, improving treatment collaboration,
      reducing relapse rates and enhancing functional recovery. CONCLUSION: SACBT can
      aid therapists in providing "whole person" care and achieving better global
      outcomes for patients with psychological illness.

PMID- 15715761
TI  - Introducing a professional development programme to a rural area mental health
      service: the importance of context.
AB  - OBJECTIVE: To describe the introduction of an ongoing professional development
      programme for clinicians in a rural area mental health service. The programme
      involved a series of workshops delivered by clinical psychologists. The training
      component of each workshop focused on discrete cognitive behavioural strategies,
      targeted at the amelioration of anxiety and mood symptoms. CONCLUSIONS: The paper
      emphasizes contextual aspects of the programme: its setting, the modality of
      delivery, resourcing issues and maximizing engagement by the participants.
      Preliminary evaluation data are reviewed, and it is argued that programmes that
      focus on local capacity building in rural settings are an important component of
      redressing the urban-rural imbalance in the availability of evidence-based
      psychological treatments.

PMID- 15715762
TI  - The Medical Specialist Outreach Assistance Programme in South Australia at 2
      years.
AB  - OBJECTIVE: To describe the progress and achievements of the psychiatric services
      developed by the Medical Specialist Outreach Assistance Programme in South
      Australia over the last 2 years. There is a particular focus on services provided
      to the remote areas of the far northern region of South Australia. CONCLUSION:
      During this period there has been an expansion of visiting psychiatric services
      to South Australia's rural and remote communities. In particular, child and
      Indigenous services have improved considerably. These have been important
      developments and it is hoped that funding and services will continue after the
      June 2004 conclusion of the Medical Specialist Outreach Assistance Programme.

PMID- 15715763
TI  - Parenting is a mental health issue.
AB  - OBJECTIVE: Increasing numbers of adults with a psychiatric disorder are also
      parents of dependent children. The present article aims to outline ways in which
      Fellows of the Royal Australian and New Zealand College of Psychiatrists (RANZCP)
      can assist in enhancing psychiatric care when a person with a mental illness also
      has parenting responsibilities. METHODS: The national Children of Parents With A
      Mental Illness (COPMI) initiative undertook consultations with consumers, carers,
      young people and a range of professionals to assist in development of documents
      and resource materials to enhance policy and practice. Communication and
      interaction with key psychiatrists' professional bodies to seek their advice and
      participation has been maintained throughout the project. RESULTS: The RANZCP
      Fellows have assisted the COPMI project in the development and dissemination of
      draft principles and recommended actions for services and people working with
      children of parents with a mental illness and their families, and in the
      development of associated resource materials. They are now considering a College
      position statement on this issue. CONCLUSIONS: If children of parents with a
      mental illness are to benefit from proposed enhancements to practice relating to
      services provided to their families, it is essential that psychiatrists
      themselves are involved in the development, implementation and review of good
      practice in this area.

PMID- 15715764
TI  - Possibilities and realities: South Australia's asylums in the 19th century.
AB  - OBJECTIVE: To provide a brief overview of the provisions for the mentally ill in
      the 19th century in South Australia, and to highlight how this history and the
      provisions made have affected the design of modern psychiatric hospitals in the
      State. CONCLUSIONS: In the 19th century, new ideas about treatment of the
      mentally ill led to a focus on the provision of care within the setting of the
      lunatic asylum. Although there were opportunities to provide the best possible
      asylum environment, the reality was that the provisions made fell far short of
      what was needed, and in turn reflects the effects of economics on the care
      provided for the mentally ill. These 19th century asylums provided the basis of
      many modern psychiatric hospitals, and the design problems found in these earlier
      buildings continue, offering limited physical spaces for the patients residing in
      these places.

PMID- 15715765
TI  - "Antwone Fisher": how dangerous is "Dr Wonderful"?
AB  - OBJECTIVE: To describe the style of psychotherapy portrayed in the film "Antwone
      Fisher". The rationale for this examination is that prospective patients often
      have little idea about what the process of psychotherapy may involve; depictions
      of therapy in popular films and on television serve to "prime" our patients'
      expectations in this regard. CONCLUSIONS: The film in question shows a
      psychiatrist who might be readily perceived as unambiguously good by a lay
      audience, despite a number of clear therapeutic boundary violations occurring
      throughout the film. Although such positive depictions might enhance the public
      image of psychiatry, they have the potential to create unreal expectations within
      patients and to promote the acceptability of boundary violations.

PMID- 15715766
TI  - Bloomsday 100: the making of a literary legend.
AB  - OBJECTIVE: As a background to the centenary of Bloomsday, to explore the
      circumstances in which James Joyce wrote "Ulysses", noting the autobiographical
      elements and unique style, including the stream-of-consciousness technique that
      depicted the inner life of the characters. Selected quotations are used to
      illustrate these points. Joyce wanted to show that the epic and the heroic is in
      our lives every day. CONCLUSIONS: "Ulysses" defined the literary consciousness of
      the 20th century. By basing the novel about a day in the life of three ordinary
      characters on Homer's epic account of an 18 year voyage, Joyce re-established the
      link between 20th century consciousness and classical times.

PMID- 15715770
TI  - Clinical practice guidelines.

PMID- 15715771
TI  - Clinical practice guidelines.

PMID- 15715774
TI  - The future revealed?

PMID- 15715772
TI  - Preventable deaths.

PMID- 15715775
TI  - Trajectory of response to antidepressants: a call for psychiatrist investigators.

PMID- 15715776
TI  - Seduction in the forensic evaluation.

PMID- 15715777
TI  - Australia needs a mental health commission.
AB  - OBJECTIVES: The present paper aims to: (i) describe how the Mental Health
      Commission in New Zealand works and has contributed to the substantial
      enhancement of mental health resources and services; (ii) determine whether
      mental health reform policies will ever be implemented properly without an
      independent monitor with official influence at the highest levels of government;
      and (iii) demonstrate how variants on this model work in other Western countries
      and how it can be adapted to the Federated system in Australia. CONCLUSIONS: It
      is recommended that the Australian National Mental Health Plan 2003-2008 should
      be complemented by a long-standing national mental health commission (or
      similarly constituted body), which is also able to report independently from and
      to the government, with direct access to the Prime Minister, Premiers and
      Australian Health Ministers. Its aims would be to monitor service effectiveness
      and identify gaps in service provision, training and performance of the work
      force, management and government. It would be informed by consumer, carer and
      provider experience, and by reviews of evidence-based research regarding health
      needs and cost-effective services. It should accurately cost such service gaps,
      and advise government on a strategy for implementing them. It could also promote
      and advise formally on enhancing community awareness, decreasing stigma and
      discrimination and improving workforce recruitment and retention.

PMID- 15715778
TI  - Partnerships between academic psychiatry and the pharmaceutical industry: the
      Lilly MAP Initiative.
AB  - OBJECTIVE: To examine the relationship between academic psychiatry and the
      pharmaceutical industry, focusing on a partnership between academics in Melbourne
      and Eli Lilly and Company (Lilly Melbourne Academic Psychiatry). CONCLUSIONS:
      Relationships between the pharmaceutical industry and the medical profession
      (including psychiatry) are under scrutiny as never before. Despite the complex
      nature of the relationship, the present paper argues that partnerships with
      external corporations such as pharmaceutical companies are of increasing
      importance for academic departments of psychiatry and research institutes, in
      environments in which core funding for tertiary institutes is being reduced. The
      partnership between Melbourne psychiatric academics and Eli Lilly and Company
      shows that benefits accrue to both parties, and suggests that there is a
      worthwhile place for other industry- academic collaborations of a similar nature
      in Australia.

PMID- 15715780
TI  - Audit of antipsychotic prescribing in a private psychiatric hospital.
AB  - OBJECTIVES: There exists a substantial and growing body of evidence suggesting
      that antipsychotic medications are efficacious in the treatment of many non
      psychotic psychiatric disorders. Although indications for the use of
      antipsychotics (particularly the atypicals) remain relatively narrow in
      Australia, psychiatrists seem to be using them for an expanding range of
      disorders in a variety of clinical settings. This has raised issues of cost
      effectiveness and methods of funding of these medications. The present study
      aimed to quantify and describe the patterns of prescribing of antipsychotic
      medications in a large private psychiatric hospital. Another aim was to compare
      the findings with other published evidence, and consider the implications of
      antipsychotic use for current clinical practice in Australia. METHODS: A
      retrospective review of the medical records of 100 consecutive patients admitted
      to a private psychiatric hospital was conducted. The data collected included
      demographic details, major psychiatric diagnoses, all medications prescribed
      during the admission and their doses and, in the case of antipsychotics, the
      target symptoms/conditions for which they were prescribed. RESULTS: Fifty-nine
      per cent of inpatients received at least one dose of an antipsychotic during
      their admission. While all patients with psychotic illnesses were treated with
      antipsychotics, 57% of patients with primary mood disorders and 40% of patients
      with a primary anxiety disorder also received an antipsychotic. The most common
      indications for use of antipsychotics included the treatment of psychotic
      symptoms, augmentation of antidepressants, relief of anxiety symptoms and
      lessening of agitation, and control of difficult behaviours (including self-harm
      and aggression) associated with personality disorders. The most frequently used
      antipsychotic was olanzapine (22%), followed by chlorpromazine (20%), and
      quetiapine (14%). Eleven per cent of patients received a combination of two
      antipsychotics. CONCLUSIONS: Antipsychotic medications were widely used in a
      private psychiatric inpatient setting for the treatment of non-psychotic
      disorders. This finding parallels those from other Australian studies of
      psychotropic prescribing patterns. The issues of clinical utility, cost
      effectiveness and benefits of funding of these medications for such wider
      indications require further study and evaluation.

PMID- 15715781
TI  - Repetitive transcranial magnetic stimulation and electroconvulsive therapy:
      complementary or competitive therapeutic options in depression?
AB  - OBJECTIVE: To examine issues pertaining to the potential clinical roles of
      repetitive transcranial magnetic stimulation (rTMS) and the relationship of these
      to the use of electroconvulsive therapy (ECT). METHODS: A review of studies was
      carried out comparing the use of rTMS and ECT, with consideration of issues
      relating to the populations in which rTMS may be applied. RESULTS: There have
      been a number of randomized comparisons of rTMS and ECT. There are limitations
      with these studies, but in general they indicate that in non-psychotic patients
      rTMS appears to have a similar rate of response to ECT and certainly seems to
      have meaningful clinical effects. There are a number of clinical subpopulations
      in whom rTMS, but not ECT, is suitable, and assessment of the effectiveness of
      TMS in these populations is required. CONCLUSIONS: Repetitive TMS and ECT are
      likely to prove to be complementary clinical tools and the introduction of
      clinical programmes with rTMS will enhance patient options rather than replace
      the use of ECT.

PMID- 15715782
TI  - Anna O and Hanna Q.
AB  - OBJECTIVE: To review the case of Anna O in light of perspectives offered by Dr
      Kaplan in his paper 'O Anna: being Bertha Pappenheim--historiography and
      biography' and to compare it with a contemporary case, that of Hanna Q.
      CONCLUSIONS: Josef Breuer's initial diagnoses do not need revision. However, the
      aetiology of such diagnoses is informed by subsequent research and by comparison
      with contemporary cases that can quite closely resemble that of Anna O's. Her
      symptomatology was not unique.

PMID- 15715783
TI  - Dissociative disorders: a personal 'work in progress'.
AB  - OBJECTIVE: To identify the core issues contained within the dissociative
      disorders literature, and synthesize them into a non-polarized, inclusive
      perspective that emphasizes logic, core psychological principles and mutual
      professional respect. CONCLUSIONS: A large percentage of all psychiatric patients
      are traumatized in clinically significant manners. Dissociation, in all its
      variants, represents a psychological mechanism for the victim of trauma to defend
      him/herself from being overwhelmed. Debates regarding the validity of
      dissociative disorders need to be viewed in the context of society's counter
      transference to trauma, in the context of health professionals feeling vulnerable
      to controversy, and in terms of their own experience of trauma.

PMID- 15715784
TI  - The psychological impact of September 11 terrorism on Australian inpatients.
AB  - OBJECTIVE: To investigate the psychological impact on Australian hospital
      patients of the media coverage of the September 11 (9/11) terrorist attack.
      METHODS: Thirty psychiatry and 26 matched medical and surgical inpatients were
      assessed. RESULTS: Both reported and observed distress was common. Women reported
      significantly more distress than men. Individuals with psychiatric illness were
      significantly more varied in their attribution of cause for 9/11. Seven patients
      (29%) with pre-existing psychosis became delusional surrounding the events, but
      there were no significant differences between the psychiatry and the medical and
      surgical inpatients. CONCLUSIONS: Clinical impressions were confirmed, namely,
      that a large proportion of hospital inpatients were adversely affected by TV
      footage of the 9/11 terrorist attack. Most vulnerable were those already with a
      mental disorder, particularly those with a pre-existing psychotic illness.

PMID- 15715785
TI  - A tale of three pathways: the experience of RBWH Mental Health.
AB  - OBJECTIVES: Australian research has identified that there are significant
      variations between service providers in terms of clinical management of patients
      with comparable presenting problems. Internal audits within the facility at Royal
      Brisbane and Women's Hospital revealed that these variations occurred between
      wards, treating teams and psychiatric consultants. Given the increasing emphasis
      on evidence-based practice, it was decided that the literature should be reviewed
      to determine what the standard of care should be. The paper then examines how
      clinical pathways for psychosis and for depression were developed and how they
      eventually evolved into an acute inpatient pathway. It identifies the framework
      used and examines important aspects relating to the adaptation of these
      frameworks to mental health issues. The process for the development and
      implementation of the clinical pathway is discussed. Recommendations for their
      future use in a mental health setting are also presented. CONCLUSIONS: Mental
      Health care is complex. For this reason, mental health clinical pathways have to
      remain flexible and innovative. With the present project, it was found that the
      pathways were not suited for specific diagnoses so that they evolved into a
      single acute inpatient pathway.

PMID- 15715786
TI  - Forgiveness as a secondary prevention strategy for victims of interpersonal
      crime.
AB  - OBJECTIVE: The number of violent crimes against people is increasing. The present
      paper aimed to review (i) the association between 'unforgiveness' among victims
      and psychiatric disease; and (ii) evidence that encouraging forgiveness can help
      to prevent psychiatric disease. CONCLUSIONS: Unforgiveness correlates strongly
      with the development of psychiatric disease. Encouraging forgiving attitudes and
      emotions leads to decreased anxiety and depression.

PMID- 15715788
TI  - Responding to serious and complex mental health problems in youth: the role of an
      interagency forum.
AB  - OBJECTIVE: To review the origins, processes, clientele and outcomes of a child
      and youth interagency forum, a collaborative response to children and youth with
      severe and complex presentations. METHODS: After a description of the Forum
      origins, membership and processes, both qualitative and quantitative information
      is provided on the Forum clientele. The Forum's effectiveness is considered in
      terms of changes in services provided to this group, as well as changes in agency
      and interagency work practices. RESULTS: Forum clients were predominantly boys
      aged 12 years, with an overrepresentation of indigenous and intellectually
      disabled children. Few lived with biological parents, and on average had
      experienced five schools, 11 or more residential placements and were involved
      with six agencies. Disruptive behaviour symptoms were common, as were suicidal
      thoughts or actions (43%), history of physical (50%) or sexual abuse (21%),
      alcohol (29%) and drug use (14%). On average Forum clients were taking three
      psychotropic medications. Forum client impairment ranged from major impairment to
      gross impairment across several domains. CONCLUSIONS: While this is not a formal
      outcome study, evidence suggesting Forum usefulness included qualitative feedback
      from agencies, altered clinical and interagency practices, and decreased client
      impairment. Practical interventions for clients with chronic, complex multidomain
      impairments are discussed in the context of current Australian child and
      adolescent mental health services.

PMID- 15715789
TI  - Evaluation of a rural telepsychiatry service.
AB  - OBJECTIVE: To evaluate a telepsychiatry clinical service to Wagga Wagga in rural
      New South Wales, comprising a face-to-face interview with a psychiatrist followed
      by a telepsychiatry interview with a Sydney-based psychiatrist. METHODS: Thirty
      one patients were referred to a specialist mood disorder clinic in a rural
      setting for consultation and assessment. A retrospective evaluation was made to
      determine the acceptance of the teleconferenced psychiatry and face-to-face
      psychiatry, as well as the overall patient response. RESULTS: Twenty participants
      completed all evaluation components. Their results indicated a satisfaction level
      of 95% with the consultation process as a whole, with 80% happy to use
      telepsychiatry again and 60% preferring telepsychiatry over travelling to a
      larger centre for face-to-face consultation. The face-to-face component was
      satisfactory for 85% of patients while the telepsychiatry component was
      satisfactory for 72%. CONCLUSIONS: Although face-to-face psychiatry was preferred
      by this sample, the telepsychiatry component was highly rated and preferred over
      travel to larger centres for face-to-face consultation, by residents of rural and
      remote locations. Certain issues are of more concern in telepsychiatry than face
      to-face psychiatry, including confidentiality, rapport, explanation and
      education.

PMID- 15715790
TI  - Description and evaluation of an up-skilling workshop for rural and remote mental
      health practitioners in South Australia.
AB  - OBJECTIVE: In response to the identified need for up-skilling in psychiatry for
      rural and remote general practitioners, a series of workshops has been designed
      and delivered to medical and nursing staff in South Australia. In this paper one
      such workshop is described, dealing with acute psychiatric care. Quantitative and
      qualitative evaluations of the workshop are reported on, and recommendations are
      made for future training programmes. CONCLUSIONS: The workshop was well received
      and increased participants' knowledge about the management of acute psychiatric
      presentations. Qualitative data indicate that the pharmacological management and
      neurobiology of psychiatric illness was interesting but difficult for some
      participants, and further training in these areas may be appropriate in future
      workshops. Inclusion of all professional stakeholders in future training is
      recommended, including students, to promote interest in working in rural and
      remote health. Participants considered networking with colleagues as an important
      benefit of the workshop. Targeted training in psychiatry may be needed for
      overseas-trained doctors. Further, rigorous research is needed to evaluate the
      long-term benefits of up-skilling workshops, and to inform funding bodies as to
      where resources might be most effectively channelled.

PMID- 15715791
TI  - The psychological impact of complaints and negligence suits on doctors.
AB  - OBJECTIVE: To describe the psychological impact of complaints and negligence
      litigation on doctors. METHODS: A review of the literature from 1966 to 2003 was
      conducted. Additional sources were obtained from targeted experts and
      organizations. RESULTS: Doctors who have been sued or who have had formal
      complaints made against them describe the process as an extremely stressful
      experience. Depression and adjustment disorder were relatively common, while drug
      and alcohol abuse, physical illness and suicidal ideation were reported less
      frequently. The majority of doctors who have been the subject of a complaint or
      law suit practice more 'defensively'. CONCLUSIONS: A complaint or law suit is
      uncommon in the daily practice of doctors, yet in today's medicolegal environment
      they pose a constant potential threat. The threat of, or actual, legal process
      can cause psychological, physical and behavioural practice changes. The
      obsessional personality of many doctors may make them particularly vulnerable to
      seeing the process as a challenge to their professional and personal identity.

PMID- 15715793
TI  - A guide to the Internet for psychiatrists.
AB  - OBJECTIVE: To provide psychiatrists with a guide to using the Internet.
      CONCLUSIONS: The key to using the Internet is to have the skills to keep the
      signal-to-noise ratio high. This requires knowledge and practice. The paper
      contains tips on searching and information about surfing skills, noticeboards,
      portals and email lists, and lists a range of very useful websites.

PMID- 15715795
TI  - Treatment of borderline personality disorder.

PMID- 15715796
TI  - Election of college president.

PMID- 15715797
TI  - Humphrey Osmond.

PMID- 15715798
TI  - Abolishing waiting lists in an aged psychiatry service.

PMID- 15715801
TI  - Walking the tightrope: perception, fact and inquiry.

PMID- 15715802
TI  - In conversation with Dr Albert Ellis (interview by George Halasz).

PMID- 15715803
TI  - Administrators: masters or servants?
AB  - OBJECTIVE: To question the role of medical administrators of mental health
      services. CONCLUSIONS: The primary allegiance of medical administrators should be
      to patients and the clinicians who care for them, not to politicians and those
      who hold the purse strings.

PMID- 15715805
TI  - Establishing and running a trauma and dissociation unit: a contemporary
      experience.
AB  - OBJECTIVE: To evaluate the functioning of a trauma and dissociation unit that has
      run for the past 8 years in a private hospital, with particular regard to
      operating philosophy, operating parameters, challenges encountered, research and
      educational initiatives, and the applicability of the treatment model to other
      settings. CONCLUSIONS: Despite the challenges associated with significant
      difficulties in the corporate management of a private health-care system, it has
      been possible to operate an inpatient and day hospital programme tailored to the
      needs of patients in the dissociative spectrum, and the lessons learnt from this
      experience are valid considerations in the future planning of mental health
      services overall.

PMID- 15715806
TI  - Use of seclusion in a psychiatric acute inpatient unit.
AB  - OBJECTIVE: To examine the rate and characteristics of seclusion among a group of
      patients admitted to an adult acute psychiatric unit as a precursor to planning
      an audit cycle and quality improvement project. METHODS: A retrospective chart
      review of all inpatient admissions to an adult acute unit over a 12 month period
      was undertaken with the use of a specially developed proforma. A comparison of
      secluded and non-secluded patients was described, and, where possible,
      statistically analysed. RESULTS: Four hundred and fifty admissions occurred
      during the study period, resulting in 140 episodes of seclusion. This represented
      a seclusion rate of 31% per admission. In contrast to patients who were not
      secluded, those secluded were more likely to be young, admitted involuntarily and
      with a diagnosis of schizophrenia. The most common indicator of seclusion was
      risk to others (74%) followed by risk to self (61%) and risk of absconding (55%).
      Length of time in seclusion ranged from 1 to 49 h with a mean of 9 h. Thirty-nine
      per cent of secluded patients were secluded on two or more occasions.
      Interventions including counselling, time out and medication were used in 71%
      prior to seclusion; however, in 29% no intervention was documented. Seclusion was
      more likely to occur in the evenings, when staff/patient ratios were lower.
      CONCLUSION: Seclusion remains an important part of psychiatric practice. As
      expected, the use of seclusion in an adult acute unit reflected indirect measures
      of illness severity. Its use needs to be carefully reviewed and monitored,
      representing as it does the greatest restriction on a person's freedom.

PMID- 15715808
TI  - Clinical decision support systems in psychiatry in the Information Age.
AB  - OBJECTIVE: Clinical decision support systems (CDSSs) are active knowledge systems
      that use two or more items of patient data to generate case-specific advice. They
      were developed to improve health-care quality. There is evidence that they can be
      a valuable tool in fostering the process of dissemination and uptake of clinical
      guidelines that, in turn, can improve clinical decision-making and outcomes. The
      present paper will explore why, despite this potential, CDSSs have not been
      extensively used in psychiatry. CONCLUSIONS: There is an abundant literature that
      explores the barriers to the development and implementation of information
      technology in health. This can be understood as related to clinician,
      organizational, cultural and technological factors. Certain characteristics of
      the clinical discipline of psychiatry present an additional barrier, although
      diagnostic systems appear to have gained a level of acceptance.

PMID- 15715807
TI  - Changeability, confidence, common sense and corroboration: comprehensive suicide
      risk assessment.
AB  - OBJECTIVE: The authors, in collaboration with NSW Health, have recently developed
      a comprehensive suicide risk assessment framework. The present paper describes
      key concepts in the assessment of suicide risk by mental health professionals.
      METHODS: A framework for conducting a comprehensive suicide risk assessment was
      derived from the literature, incident analysis and clinical experience. The
      framework underwent a consultation process involving clinicians in NSW area
      mental health services. The aim was to provide clinicians with a standardized
      conceptual map for the assessment of suicide risk. A MEDLINE search was conducted
      for publications dealing with 'suicide' and 'suicide risk assessment' from 1980
      to 2002. The recommendations from sentinel event reviews conducted in a NSW area
      mental health service in the period 1999-2002 were reviewed. The lessons from a
      visit to a coroner's relatives support group for people who had been bereaved by
      suicide also informed the development of the guidelines. RESULTS: A framework is
      proposed for the assessment of suicide risk. The framework promotes a reflective
      style of practice, encouraging clinicians to evaluate their assessment and its
      limitations. Risk assessment is always undertaken as part of a full clinical
      assessment and an evaluation of the person's current predicament and psychosocio
      cultural context. The concepts of changeability, assessment confidence, common
      sense and the importance of corroboration are incorporated in the framework.
      CONCLUSIONS: Mental health clinicians can be guided by a framework in suicide
      risk assessment and documentation. The assessment of suicide risk can generate a
      suicide risk rating for which minimum standards of care can be mandated.

PMID- 15715809
TI  - Use of the psychiatric consultation letter as a therapeutic tool.
AB  - OBJECTIVE: Carefully crafted medical consultation letters can serve the dual
      purpose of transmitting the consulted psychiatrist's opinion to the referring
      doctor and enhancing the quality of the doctor-patient therapeutic relationship.
      Using the same document for both purposes simultaneously can enhance the
      consultation letter's overall effectiveness, as illustrated by three case
      examples. CONCLUSIONS: Future teaching programmes for undergraduate and
      postgraduate psychiatry students should incorporate consultation letter writing
      workshops to improve students' skills in clearly expressing their opinions and
      management recommendations in written form.

PMID- 15715810
TI  - Review of new compounds available in Australia for the treatment of attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: To examine the pharmacodynamic and pharmacokinetic properties,
      efficacy, safety and cost of Ritalin LA, Concerta and Strattera, three compounds
      recently released in Australia for the treatment of attention-deficit
      hyperactivity disorder (ADHD). METHODS: MEDLINE was searched for relevant review
      articles and primary treatment studies. Data were augmented by product
      information supplied by the respective manufacturers. Costing information was
      obtained by surveying five community pharmacy outlets in Newcastle-Lake
      Macquarie, New South Wales. RESULTS: The three compounds reviewed have similar
      tolerability and efficacy to immediate-release methylphenidate, with the
      advantage of once daily dosing. The properties of these agents, particularly
      Strattera, make them less able to be abused. Ritalin LA may be superior to
      Concerta in controlling symptoms of ADHD in the first 4 h following ingestion,
      but the data should be interpreted with caution. CONCLUSIONS: The newer
      treatments for ADHD offer advantages over immediate-release methyphenidate in
      dosing schedule and duration of action that may be of particular benefit to
      adolescent and adult patients. Prescription of these medications may be limited
      by their expense to the patient.

PMID- 15715811
TI  - Psychostimulant treatment of adults with mental retardation and attention-deficit
      hyperactivity disorder.
AB  - OBJECTIVE: To examine the potential effectiveness and tolerability of
      psychostimulants in adults with mental retardation (MR) and attention-deficit
      hyperactivity disorder (ADHD). METHODS: A retrospective chart review was
      conducted in a clinic specialized in treating individuals with developmental
      disabilities. Improvement was assessed using the Aberrant Behaviour Checklist
      Community Version (ABC-C) and the global improvement item of the Clinical Global
      Impression scale. RESULTS: Ten consecutive adult outpatients were identified.
      Five were judged to be responders, based on impressions from chart review and the
      ABC-C. Significant improvements were observed in the hyperactivity and
      irritability subscales of the ABC-C. Adverse events were minimal and no patients
      required treatment termination. CONCLUSIONS: Psychostimulants might be effective
      and well-tolerated in the treatment of ADHD in adults with MR. However, larger
      prospective open-label studies, and, eventually, double-blind placebo-controlled
      studies are needed to confirm these findings.

PMID- 15715812
TI  - Psychiatry and Islam.
AB  - OBJECTIVE: To explore psychiatry in Islam, with a view to informing Western
      psychiatrists working with Islamic patients, and Islamic medical students
      studying in Western countries. METHODS: The first necessary step was to acquire
      some understanding of Islam, Sharia and Sharia law, as the basis on which the
      available psychiatric literature was considered. Standard textbooks on Islam and
      English-language papers in the psychiatric literature were examined. Discussions
      with knowledgeable Muslim people were conducted. RESULTS: Islam shares roots with
      the other Abrahamic, monotheistic religions: Judaism and Christianity. A central
      issues is unity: the unity of God, unity with God and unity within the Islamic
      community. Islam is more than a religion, because it informs all aspects of
      behaviour and has been described as 'a comprehensive way of life'. Individualism
      is less important than the welfare of the community. The Sharia is a list of
      rules and regulations derived from authentic sources. Psychiatric services in
      Islam, according to Western standards, are somewhat limited. This issue is being
      addressed through epidemiological studies, provision of new services and policy
      development. Although mental health legislation is not universal, forensic
      psychiatry has a role, in many ways similar to that in the West. CONCLUSION:
      Islam is based on unity and core values of compassion, justice and benevolence.
      Islamic psychiatry has a proud early history, and advances are occurring. There
      is an opportunity for the profession of psychiatry to bridge religious, ethnic
      and cultural boundaries.

PMID- 15715813
TI  - Pilot study investigating the effect of intercessory prayer in the treatment of
      child psychiatric disorders.
AB  - OBJECTIVE: To investigate whether intercessory prayer had an effect on the
      outcomes of a group of children with psychiatric conditions, using a triple blind
      randomized study design. CONCLUSION: This study was unable to show any additional
      benefits for patients who received intercessory prayer compared to those who
      received treatment as usual.

PMID- 15715814
TI  - Towards a needs based mental health resource allocation and service development
      in rural and remote Australia.
AB  - OBJECTIVE: To develop a transparent, needs-based mental health resource
      allocation framework to guide area level service planning in rural and remote
      settings. METHODS: Using the Central Australian mental health service region as a
      case study, a five-step approach was used to analyse and gather relevant data as
      follows: (i) mapping a regional sociodemographic profile; (ii) estimating the
      expected level of mental illness within the regional population; (iii) estimating
      the expected level of specialist mental health service usage; (iv) estimating the
      expected categories of specialist mental health care required for the regional
      population; (v) making adjustments to the costs of providing specialist mental
      health care on the basis of demographic features of the region. These data were
      then matched with the availability, access and cost of specialist mental health
      care currently provided at the regional level. RESULTS: The capacity of
      specialist mental health care in Central Australia was below the expected
      benchmark for the population residing in this region. The region required
      approximately double the existing funding allocation to provide an adequate and
      equitable level of care that meets the needs of the diverse population groups.
      Children and adolescents were the group most in need, as were adult Aboriginal
      people living in remote settings. CONCLUSION: The framework described provides
      the beginnings of more open and transparent evidence-based decision-making
      regarding mental health resource allocation and service development for rural and
      remote residents.

PMID- 15715815
TI  - Gundhu Adolescent Wing: providing adolescent beds in a rural acute mental health
      unit.
AB  - OBJECTIVE: To describe the evolution, structure and outcomes of Gundhu Adolescent
      Wing, Toowoomba, Queensland, which comprises six dedicated beds set aside during
      development of a new rural acute mental health unit. METHODS: All adolescents
      discharged from Gundhu in its first 7 months were included in the study. Data
      pertaining to patient characteristics, model of service delivery, length of
      inpatient stay and outcome at 7 months were obtained. RESULTS: Thirty-three
      adolescents with mental illness living in the rural area were discharged from
      Gundhu in the first 7 months. For the 23 adolescents who stayed on the unit <14
      days, outcome at 7 months after discharge was generally favourable. Six
      adolescents with length of stay of >or=30 days did less well, but made similar
      progress to patients in tertiary units. CONCLUSIONS: From the authors'
      experience, designating a small number of beds as adolescent within a rural acute
      mental health unit is an effective intervention for short-stay patients and is
      valued by adolescents and their families. Keeping the adolescent unit separate is
      beneficial even at the expense of foregoing access to space and facilities
      enjoyed by adult patients. Involving families early to provide off-ward fun,
      exercise and socialization with peers is important. Rural services tend to have
      high staff turnover. Involving rural general practitioners in follow-up plans may
      ensure better continuity of care after discharge.

PMID- 15715816
TI  - A perspective on the problems in retaining psychiatrists in New Zealand.

PMID- 15715817
TI  - Predicting the depression researcher: initial investigations.

PMID- 15715819
TI  - Transcranial magnetic stimulation: promise for the future?

PMID- 15715818
TI  - Acute psychosis following ingestion of 'Rapture'.
AB  - OBJECTIVES: To describe a brief psychotic episode associated with ingestion of a
      dietary supplement containing piperazine. METHODS: A case report was undertaken.
      RESULTS: A 20-year-old man developed a brief psychotic episode associated with
      persecutory delusional beliefs and auditory and visual hallucinations, leading
      him to commit the offence of arson. This episode occurred 12 h following the
      ingestion of 'Rapture' in addition to small quantities of cannabis and nitrous
      oxide, in a young man with no prior psychiatric history. This episode resolved
      with the use of benzodiazepines and 6 months later he has had no recurrence of
      psychiatric symptoms. CONCLUSIONS: Given the reported mechanism of action of the
      'herbal high' dietary supplements, it would seem possible that they may be able
      to precipitate a psychotic episode in vulnerable individuals. With the increasing
      use of these substances, it is important for clinicians to be alert to this
      possibility.

PMID- 15715820
TI  - Movement disorders and the treatment of schizophrenia.

PMID- 15715821
TI  - Epileptic seizure in GHB withdrawal.

PMID- 15715822
TI  - Is anger an excuse?

PMID- 15715823
TI  - Somatoform deception.

PMID- 15715824
TI  - Reducing the Social and Economic Burdens of Depression (SEBoD) in Asia.

PMID- 15715825
TI  - The economic burden of depression and reimbursement policy in the Asia Pacific
      region.
AB  - OBJECTIVE: To determine the economic burden of depression in the Asia Pacific
      region, review the negative economic consequences attributable to depression, and
      describe the reimbursement policies for health-care services throughout the Asia
      Pacific region. METHODS: Both direct and indirect costs were obtained via a
      literature review of international mental health journals. Disability adjusted
      life year (DALYs) estimates were obtained from the World Health Organization.
      Reimbursement policy data were obtained from personal communication with the
      SEBoD International Advisory Board. RESULTS: There are only two studies of the
      economic costs of depression in the Asia Pacific region. From these, the total
      cost of depression in Australia for 1997-98 was estimated as US$1.8 billion (22%
      direct costs), and in Taiwan for 1994 as US$1.4 billion (25% direct costs). In
      the year 2000, it was estimated that unipolar major depression accounted for 14.2
      million DALYs in China and 22.7 million DALYs for all other Asia Pacific
      countries. The majority of Asia Pacific health-care systems have extensive
      insurance coverage, but not specific provisions for depression. However,
      relatively low overall fee schedules diminish financial barriers for outpatient
      treatment of depression. CONCLUSIONS: Untreated depression is a very costly
      disorder across the Asia Pacific region, with indirect costs constituting a
      substantial proportion. Consequently, treatment of depression should be the focus
      of policy makers to avoid major negative cost repercussions. It is encouraging
      that most Asia Pacific health service reimbursement policies enable the treatment
      of depression (especially outpatient treatment) to be relatively affordable. To
      advance this issue, the paucity of specific information on the epidemiology of
      depression, as well as service use and cost, needs to be addressed.

PMID- 15715826
TI  - A review of the legislative mechanisms available to protect the social
      participation rights of people with depression in the Asia Pacific region.
AB  - OBJECTIVE: To conduct a review of the legislative mechanisms potentially
      available to protect the social participation rights of people with depression in
      the Asia Pacific region. METHODS: Questions were sent to the SEBoD International
      Advisory Board and Internet and legal database searches were conducted to
      supplement responses from advisors. RESULTS: While it cannot be said that
      comprehensive antidiscrimination legislation in relation to disability exists in
      all countries in the Asia Pacific region, most countries have commenced the
      process. Many have implemented either human rights or antidiscrimination
      legislation and most have set up a Human Rights Commission to protect social
      participation rights and allow complaints to be lodged. CONCLUSIONS: This review
      highlighted the difference between legislation and practice. While many countries
      have enacted laws, insufficient resources have been committed to support the
      objectives to realise the protection of rights enshrined in legislation.
      Additionally, many people may not know that the laws exist or do not have the
      money or social supports to fight for their rights. Many countries, however, have
      commenced a concerted approach to tackling the larger issues and have developed
      comprehensive action plans to address the social participation rights of people
      with disability.

PMID- 15715827
TI  - A preliminary survey of undergraduate education on depression in medical schools
      in the Asia Pacific region.
AB  - OBJECTIVE: To describe the undergraduate medical curricula pertaining to
      depression across the Asia Pacific region. METHODS: Questions were sent to the
      members of the SEBoD International Advisory Board asking for details on the
      specifics of medical curricula regarding depression. RESULTS: Representatives of
      13 medical universities from eight Asia Pacific countries provided information.
      All curricula include psychiatry lectures, and most countries also conduct
      seminars and tutorials. Provision of clinical experience is common, but not all
      curricula include specific presentation of cases of depression. Within the
      psychiatry courses reviewed, only a small component of teaching is related
      specifically to depression. CONCLUSIONS: As there is growing recognition of the
      burden of depression, development and implementation of national curricula
      standards are recommended to address inadequacies in teaching of depression in
      undergraduate medical universities throughout the Asia Pacific region.

PMID- 15715828
TI  - Treatment guidelines for depression in the Asia Pacific region: a review of
      current developments.
AB  - OBJECTIVE: This paper examines the development of treatment guidelines,
      medication algorithms and clinical pathway guides for depression in countries
      participating in the SEBoD Initiative. METHODS: A systematic review of the extent
      of development of treatment guidelines, medication algorithms or clinical pathway
      guides for depression in participating countries. RESULTS: Most countries in the
      Asia Pacific region have commenced the development of treatment guidelines,
      medication algorithms or clinical pathway guides. The promoters of such efforts
      have included a range of professional and government bodies. Most efforts have
      borrowed heavily on existing international guidelines. There is a significant
      emphasis on medication practices in most countries, with less emphasis on the
      role of psychological or other non-pharmacological approaches. There has been
      insufficient emphasis on integrating local classification, assessment and
      cultural practices into the provision of high quality care. Important additional
      measures, including practice surveys and consensus judgements, have been
      undertaken in some countries. CONCLUSIONS: The development of a genuine quality
      improvement movement for depression treatments is in its infancy in the Asia
      Pacific region. However, there is now the capacity to bring together such efforts
      at a regional level and, in doing so, promote standards for best care, more
      community and professional involvement and the uptake of a wider variety of
      treatment approaches.

PMID- 15715829
TI  - Can we reduce the burden of depression? The Australian experience with
      beyondblue: the national depression initiative.
AB  - OBJECTIVE: Throughout the Asia Pacific region, there is an urgent need to reduce
      the burden of depression by increasing depression awareness, reducing stigma and
      dismantling those social barriers that prevent full participation by people with
      depression. This paper describes the development and early achievements of the
      Australian depression initiative, beyondblue. METHODS: A review of the key
      priorities of beyondblue and their impacts during the first three years of
      operation (2001-03). RESULTS: Key achievements include: the degree of national
      recognition of beyondblue; size and scope of media impact; growth in website
      utilisation; increased reporting of the community's recognition of people with
      depression; genuine reforms in life insurance and income protection; development
      of a new national consumer and carer organisation; establishment of major
      population-based preventative and early intervention programs; system-wide reform
      of primary care-based mental health services; national educational program uptake
      by general practitioners; and, development of key awareness and intervention
      programs for use in schools and the workplace. CONCLUSIONS: In its first three
      years of operation, beyondblue has had a major impact on depression awareness in
      Australia and demonstrable gains have been made in reducing stigma and major
      social barriers. A pre-existing national mental health policy and implementation
      plan, a substantial funding base and participation by key political, media and
      community leaders have been essential elements of its short-term success. Its
      longer-term impact will now depend on more sustainable community and business
      partnerships as well as the growth of a more influential consumer and carer
      voice.

PMID- 15715830
TI  - Epidemiology of depression in the Asia Pacific region.
AB  - OBJECTIVE: To summarise studies reporting rates of depression (for the general
      population and older samples) and suicide in the Asia Pacific region. METHODS:
      Information on local data was collected from the members of the SEBoD
      International Advisory Board on known epidemiological studies. Additionally,
      online searches were conducted using Medline and PsycInfo for the period 1994
      2004. RESULTS: Across the Asia Pacific region, rates of current or 1-month major
      depression ranged from 1.3% to 5.5%, rates of major depression in the previous
      year ranged from 1.7% to 6.7%, and lifetime rates ranged from 1.1% to 19.9%, with
      a median of 3.7%. Rates of suicide in the Asia Pacific region are now similar to
      those in Europe and the Americas. The exceptions include China and South Korea.
      CONCLUSIONS: Epidemiological studies in Asian populations are rare and use
      various diagnostic criteria. However, studies indicate that rates of depression
      in Asia Pacific, whilst lower, are comparable to other western countries. As
      such, depression as a health issue in Asia Pacific demands greater recognition.
      It is important that Asian countries should have the human and financial
      resources to conduct large scale epidemiological surveys not only in the area of
      depression, but also in the broader field of mental disorders.

PMID- 15715831
TI  - Hybrid incompatibility is consistent with a hybrid origin of Heliconius heurippa
      Hewitson from its close relatives, Heliconius cydno Doubleday and Heliconius
      melpomene Linnaeus.
AB  - Abstract Shared ancestral variation and introgression complicates the
      reconstruction of phylogenetic relationships among closely related taxa. Here we
      use overall genomic compatibility as an alternative estimate of species
      relationships in a group where divergence is rapid and genetic exchange is
      common. Heliconius heurippa, a butterfly species endemic to Colombia, has a
      colour pattern genetically intermediate between H. cydno and H. melpomene: its
      hindwing is nearly indistinguishable from that of H. melpomene and its forewing
      band is an intermediate phenotype between both species. This observation has lead
      to the suggestion that the pattern of H. heurippa arose through hybridization. We
      present a genetic analysis of hybrid compatibility in crosses between the three
      taxa. Heliconius heurippa x H. cydno and female H. melpomene x male H. heurippa
      yield fertile and viable F1 hybrids, but male H. melpomene x female H. heurippa
      crosses yield sterile F1 females. In contrast, Haldane's rule has previously been
      detected between H. melpomene and H cydno in both directions. Therefore, H.
      heurippa is most closely related to H. cydno, with some evidence for
      introgression of genes from H. melpomene. The results are compatible with the
      hypothesis of a hybrid origin for H. heurippa. In addition, backcrosses using F1
      hybrid males provide evidence for a large Z(X)-chromosome effect on sterility and
      for recessive autosomal sterility factors as predicted by Dominance Theory.

PMID- 15715832
TI  - Testing alternative mechanisms of evolutionary divergence in an African rain
      forest passerine bird.
AB  - Abstract Models of speciation in African rain forests have stressed either the
      role of isolation or ecological gradients. Here we contrast patterns of
      morphological and genetic divergence in parapatric and allopatric populations of
      the Little Greenbul, Andropadus virens, within different and similar habitats. We
      sampled 263 individuals from 18 sites and four different habitat types in Upper
      and Lower Guinea. We show that despite relatively high rates of gene flow among
      populations, A. virens has undergone significant morphological divergence across
      the savanna-forest ecotone and mountain-forest boundaries. These data support a
      central component of the divergence-with-gene-flow model of speciation by
      suggesting that despite large amounts of gene flow, selection is sufficiently
      intense to cause morphological divergence. Despite evidence of isolation based on
      neutral genetic markers, we find little evidence of morphological divergence in
      fitness-related traits between hypothesized refugial areas. Although genetic
      evidence suggests populations in Upper and Lower Guinea have been isolated for
      over 2 million years, morphological divergence appears to be driven more by
      habitat differences than geographic isolation and suggests that selection in
      parapatry may be more important than geographic isolation in causing adaptive
      divergence in morphology.

PMID- 15715833
TI  - When morphometry meets genetics: inferring the phylogeography of Carabus solieri
      using Fourier analyses of pronotum and male genitalia.
AB  - Population differentiation is a crucial step in the speciation process and is
      therefore a central subject in studies of microevolution. Assessing divergence
      and inferring its dynamics in space and time generally require a wide array of
      markers. Until now however, most studies of population structure are based on
      molecular markers and those concerning morphological traits are more scarce. In
      the present work, we studied morphological differentiation among populations of
      the ground beetle Carabus solieri, and tested its congruence with genetic
      population structure. The shape of pronotum and aedeagus was assessed using Dual
      Axis Fourier Shape Analysis. manova on Fourier coefficients revealed highly
      significant morphological variation between populations and a similar
      geographical pattern of differentiation for both structures. On the whole,
      morphological and genetic patterns were also found to be congruent. Our analysis
      confirms the phylogeographical scenario proposing that two entities of C. solieri
      differentiated during the last glaciation events before recolonizing the actual
      range of the species. It also indicates a large introgression between the two
      differentiated entities in the centre of the range.

PMID- 15715834
TI  - The evolutionary genetics of egg size plasticity in a butterfly.
AB  - Abstract The evolution of phenotypic plasticity requires that it is adaptive,
      genetically determined, and exhibits sufficient genetic variation. For the
      tropical butterfly Bicyclus anynana there is evidence that temperature-mediated
      plasticity in egg size is an adaptation to predictable seasonal change. Here we
      set out to investigate heritability in egg size and genetic variation in the
      plastic response to temperature in this species, using a half-sib breeding
      design. Egg size of individual females was first measured at a high temperature 4
      days after eclosion. Females were then transferred to a low temperature and egg
      size was measured after acclimation periods of 6 and 12 days respectively.
      Overall, additive genetic variance explained only 3-11% of the total phenotypic
      variance, whereas maternal effects were more pronounced. Genotype-environment
      interactions and cross-environmental correlations of less than unity suggest that
      there is potential for short-term evolutionary change. Our findings strengthen
      the support for the adaptive nature of temperature-mediated plasticity in egg
      size.

PMID- 15715835
TI  - Sex-specific selective pressures on body mass in the greater white-toothed shrew,
      Crocidura russula.
AB  - The direction, intensity and shape of viability-, sexual- and fecundity selection
      on body mass were investigated in a natural population of the greater white
      toothed shrew (Crocidura russula), combining parentage assignment through
      molecular techniques and mark-recapture data over several generations. A highly
      significant stabilizing viability selection was found in both sexes, presumably
      stemming from the constraints imposed by their insectivorous habits and high
      metabolic costs. Sexual selection, directional in both sexes, was twice as large
      in males than in females. Our results suggest that body mass matters in this
      context by facilitating the acquisition and defense of a breeding territory. No
      fecundity selection could be detected. The direction of sexual size dimorphism
      (SSD) was in agreement with the observed pattern of selective pressures: males
      were heavier than females, because of stronger sexual selection. SSD intensity,
      however, was low compared with other mammals, because of the low level of
      polygyny, the active role of females in territory defense and the intensity of
      stabilizing viability selection.

PMID- 15715836
TI  - Selfing and resource allocation in Schiedea salicaria (Caryophyllaceae), a
      gynodioecious species.
AB  - Abstract Levels of selfing and resource allocation patterns were investigated in
      Schiedea salicaria (Caryophyllaceae), a gynodioecious species with high levels of
      inbreeding depression and nuclear control of male sterility. Selfing levels were
      higher in hermaphrodites than females, especially when adjusted for early acting
      inbreeding depression. The sexes of S. salicaria were similar in most allocation
      patterns including number of flowers and capsules per inflorescence, seeds per
      flower, and seed mass. Seeds produced by females had higher levels of germination
      than seeds of hermaphrodites, a likely result of high selfing levels and the
      expression of inbreeding depression in the progeny of hermaphrodites. Invasion of
      females in populations of S. salicaria is probably related to the expression of
      inbreeding depression at germination and in later life history stages.
      Comparisons with related species of Schiedea that also have nuclear control of
      male sterility suggest that reallocation of resources in hermaphrodites to male
      function occurs as females increase in frequency, but that resource reallocation
      is not important for the success of females when they first invade populations.

PMID- 15715837
TI  - Evolutionary traction: the cost of adaptation and the evolution of sex.
AB  - The advantage of sexual reproduction remains a puzzle for evolutionary
      biologists. Everything else being equal, asexual populations are expected to have
      twice the number of offspring produced by similar sexual populations. Yet,
      asexual species are uncommon among higher eukaryotes. In models assuming small
      populations, high mutation rates, or frequent environmental changes, sexual
      reproduction seems to have at least a two-fold advantage over asexuality. But the
      advantage of sex for large populations, low mutation rates, and rare or mild
      environmental changes remains a conundrum. Here we show that without
      recombination, rare advantageous mutations can result in increased accumulation
      of deleterious mutations ('evolutionary traction'), which explains the long-term
      advantage of sex under a wide parameter range.

PMID- 15715838
TI  - Phylogenetic congruence of mealybugs and their primary endosymbionts.
AB  - Tight interactions between unrelated organisms such as is seen in plant-insect,
      host-parasite, or host-symbiont associations may lead to speciation of the
      smaller partners when their hosts speciate. Totally congruent phylogenies of
      interacting taxa have not been observed often but a number of studies have
      provided evidence that various hemipteran insect taxa and their primary bacterial
      endosymbionts share phylogenetic histories. Like other hemipterans, mealybugs
      (Pseudococcidae) harbour multiple intracellular bacterial symbionts, which are
      thought to be strictly vertically inherited, implying codivergence of hosts and
      symbionts. Here, robust estimates of phylogeny were generated from four fragments
      of three nuclear genes for mealybugs of the subfamily Pseudococcinae, and a
      substantial fragment of the 16S-23S rDNA of their P-endosymbionts. Phylogenetic
      congruence was highly significant, with 75% of nodes on the two trees identical,
      and significant correlation of branch lengths indicated coincident timing of
      cladogenesis. It is suggested that the low level of observed incongruence was
      influenced by uncertainty in phylogenetic estimation, but evolutionary outcomes
      other than congruence, including host shifts, could not be rejected.

PMID- 15715839
TI  - The evolution of generalization? Parasitoid flies and the perils of inferring
      host range evolution from phylogenies.
AB  - It is widely assumed that high resource specificity predisposes lineages toward
      greater likelihood of extinction and lower likelihood of diversification than
      more generalized lineages. This suggests that host range evolution in parasitic
      organisms should proceed from generalist to specialist, and specialist lineages
      should be found at the 'tips' of phylogenies. To test these hypotheses, parsimony
      and maximum likelihood methods were used to reconstruct the evolution of host
      range on a phylogeny of parasitoid flies in the family Tachinidae. In contrast to
      predictions, most reconstructions indicated that generalists were repeatedly
      derived from specialist lineages and tended to occupy terminal branches of the
      phylogeny. These results are critically examined with respect to hypotheses
      concerning the evolution of specialization, the inherent difficulties in
      inferring host ranges, our knowledge of tachinid-host associations, and the
      methodological problems associated with ancestral character state reconstruction.
      Both parsimony and likelihood reconstructions are shown to provide misleading
      results and it is argued that independent evidence, in addition to phylogenetic
      trees, is needed to inform models of the evolution of host range and the
      evolutionary consequences of specialization.

PMID- 15715840
TI  - Indirect evidence from DNA sequence diversity for genetic degeneration of the Y
      chromosome in dioecious species of the plant Silene: the SlY4/SlX4 and DD44
      X/DD44-Y gene pairs.
AB  - The action of natural selection is expected to reduce the effective population
      size of a nonrecombining chromosome, and this is thought to be the chief factor
      leading to genetic degeneration of Y-chromosomes, which cease recombining during
      their evolution from ordinary chromosomes. Low effective population size of Y
      chromosomes can be tested by studying DNA sequence diversity of Y-linked genes.
      In the dioecious plant, Silene latifolia, which has sex chromosomes, one
      comparison (SlX1 vs. SlY1) indeed finds lower Y diversity compared with the
      homologous X-linked gene, and one Y-linked gene with no X-linked homologue has
      lower species-wide diversity than a homologous autosomal copy (SlAp3Y vs.
      SlAp3A). To test whether this is a general pattern for Y-linked genes, we studied
      two further recently described X and Y homologous gene pairs in samples from
      several populations of S. latifolia and S. dioica. Diversity is reduced for both
      Y-linked genes, compared with their X-linked homologues. Our new data are
      analysed to show that the low Y effective size cannot be explained by different
      levels of gene flow for the X vs. the Y chromosomes, either between populations
      or between these closely related species. Thus, all four Y-linked genes that have
      now been studied in these plants (the two studied here, and two previously
      studied genes, have low diversity). This supports other evidence for an ongoing
      degeneration process in these species.

PMID- 15715841
TI  - The geographic selection mosaic for squirrels, crossbills and Aleppo pine.
AB  - The interactions between many species are structured in a geographic mosaic of
      populations among which selection is divergent. Here we tested the hypothesis
      that such a geographic selection mosaic arises for common crossbills (Loxia
      curvirostra) feeding on seeds in the cones of Aleppo pine (Pinus halepensis)
      because of geographic variation in the occurrence of European red squirrels
      (Sciurus vulgaris). On the Iberian Peninsula, Sciurus exerted directional
      selection favouring larger cones with larger scales, which has caused cones there
      to be larger than in the Balearic Islands where Sciurus are absent. Moreover,
      cones on the Iberian Peninsula are so large that they are apparently little used
      by the relatively small-billed crossbills on the Peninsula; selection by Sciurus
      seems to have made the cones so difficult to feed on that crossbills rely mostly
      on the seeds of other conifers. Where crossbills are present but Sciurus are
      absent (Mallorca Island), cones were smaller as a result of relaxation of
      selection by Sciurus. However, cones on Mallorca had proportionally thicker
      scales in comparison to where both Sciurus and crossbills are absent (Ibiza
      Island), presumably as an adaptation against crossbill predation. Here crossbills
      specialize on Aleppo pine, have relatively large bills and have apparently
      coevolved in an arms race with Aleppo pine. These results suggest that Sciurus
      has influenced both the geographic selection mosaics for crossbills and conifers
      and the adaptive radiation of crossbills in Eurasia much like Tamiasciurus has
      done in the North America.

PMID- 15715842
TI  - Ecological components and evolution of selfing in the freshwater snail Galba
      truncatula.
AB  - The reproductive assurance hypothesis emphasizes that self-fertilization should
      evolve in species with reduced dispersal capability, low population size or
      experiencing recurrent bottlenecks. Our work investigates the ecological
      components of the habitats colonized by the snail, Galba truncatula, that may
      influence the evolution of selfing. Galba truncatula is a preferential selfer
      inhabiting freshwater habitats, which vary with respect to the degree of
      permanence. We considered with a population genetic approach the spatial and the
      temporal degree of isolation of populations of G. truncatula. We showed that
      patches at distances of only a few meters are highly structured. The effective
      population sizes appear quite low, in the order of 10 individuals or less. This
      study indicates that individuals of the species G. truncatula are likely to be
      alone in a site and have a low probability of finding a partner from a nearby
      site to reproduce. These results emphasize the advantage of selfing in this
      species.

PMID- 15715843
TI  - The influence of territoriality and mating system on the evolution of male care:
      a phylogenetic study on fish.
AB  - Evolution of male care is still poorly understood. Using phylogenetically matched
      pairs comparisons we tested for effects of territoriality and mating system on
      male care evolution in fish. All origins of male care were found in pair-spawning
      species (with or without additional males such as sneakers) and none were found
      in group-spawning species. However, excluding group spawners, male care
      originated equally often in pair-spawning species with additional males as in
      strict pair-spawning species. Evolution of male care was also significantly
      related to territoriality. Yet, most pair-spawning taxa with male care are also
      territorial, making their relative influence difficult to separate. Furthermore,
      territoriality also occurs in group-spawning species. Hence, territoriality is
      not sufficient for male care to evolve. Rather, we argue that it is the
      combination of territoriality and pair spawning with sequential polygyny that
      favours the evolution of male care, and we discuss our results in relation to
      paternity assurance and sexual selection.

PMID- 15715844
TI  - Crossing the taxonomic divide: conflict and its resolution in societies of
      reproductively totipotent individuals.
AB  - Reproduction in groups may be unequal, with one or a few individuals monopolizing
      direct reproduction assisted by nonbreeding helpers. In social insects this has
      frequently led to a pronounced queen-worker dichotomy and a loss of reproductive
      totipotency among workers. However, in some invertebrate and all vertebrate
      societies, all or most individuals remain reproductively totipotent. In these
      groups, conflicts of interest over reproduction are potentially greatest. Here,
      we synthesize previous analyses of reproductive conflict, aggression and breeder
      replacement in haplodiploid societies of totipotent individuals and extend them
      to cover diploid (vertebrate) examples. We test predictions arising from this
      approach using the best-studied invertebrate (Dinoponera queenless ants) and
      vertebrate (naked mole-rat, Heterocephalus glaber) examples, although in
      principle our analysis applies to all similar groups. We find that premature
      replacement of a parent breeder by nonbreeders (overthrow) is rare. Dominant
      coercive control of nonbreeders by the breeder is often unnecessary and honest
      signalling of breeder vitality can maintain group stability and resolve conflicts
      over reproduction. We hope that by providing an explicit transfer of social
      theory between ants and naked mole-rats we will stimulate further cross-taxonomic
      studies that will greatly broaden our understanding of sociality.

PMID- 15715845
TI  - Trade-off between male and female allocation in the simultaneously hermaphroditic
      flatworm Macrostomum sp.
AB  - Sex allocation theory for simultaneous hermaphrodites assumes a direct trade-off
      between the allocation of resources to the male and female reproductive
      functions. Empirical support for this basic assumption is scarce, possibly
      because studies rarely control for variation in individual reproductive resource
      budgets. Such variation, which can have environmental or genetic sources, can
      generate a positive relationship between male and female investment and can thus
      obscure the trade-off. In this study on the hermaphroditic flatworm Macrostomum
      sp. we tried to control for budget effects by restricting food availability in a
      standardized way and by using an inbred line. We then manipulated mating group
      size in a two-way design (two group sizes x two enclosure sizes) in order to
      induce phenotypic variation in male allocation, and expected to find an opposing
      correlated response in female allocation. The results suggest that we only
      managed to control the budget effects under some conditions. Under these the sex
      allocation trade-off emerged. Under the other conditions we found a strongly
      positive correlation between male and female allocation. We discuss possible
      causes for the observed differences.

PMID- 15715847
TI  - A comparative analysis of predator-induced plasticity in larval Triturus newts.
AB  - Species that occupy similar habitats are expected to show convergent phenotypes.
      If habitats are defined by the presence of predators, then traits that modify
      vulnerability to predation, including predator-induced phenotypic plasticity,
      should be similar within habitats. We tested this idea using larvae of six
      syntopic newt species belonging to the two Triturus clades. Behavioural
      plasticity induced by odonate predators was strongly dissimilar between the two
      main clades but similar within them. Morphological plasticity was variable among
      species, even between one pair of closely related species. A predation experiment
      tested whether differences between clades could be caused by differences in body
      size. Size-specific vulnerability differed between newts in the small-bodied and
      large-bodied clades, indicating that similar predators may affect the two clades
      differently. The results showed both similarity and dissimilarity in predator
      induced phenotypic plasticity in syntopic larval newts although theory suggests
      that divergence is unlikely in such ecologically similar species.

PMID- 15715846
TI  - Maternal genetic effects set the potential for evolution in a free-living
      vertebrate population.
AB  - Heritable maternal effects have important consequences for the evolutionary
      dynamics of phenotypic traits under selection, but have only rarely been tested
      for or quantified in evolutionary studies. Here we estimate maternal effects on
      early-life traits in a feral population of Soay sheep (Ovis aries) from St Kilda,
      Scotland. We then partition the maternal effects into genetic and environmental
      components to obtain the first direct estimates of maternal genetic effects in a
      free-living population, and furthermore test for covariance between direct and
      maternal genetic effects. Using an animal model approach, direct heritabilities
      (h2) were low but maternal genetic effects (m2) represented a relatively large
      proportion of the total phenotypic variance for each trait (birth weight
      m2=0.119, birth date m2=0.197, natal litter size m2=0.211). A negative
      correlation between direct and maternal genetic effects was estimated for each
      trait, but was only statistically significant for natal litter size (ram= 
      0.714). Total heritabilities (incorporating variance from heritable maternal
      effects and the direct-maternal genetic covariance) were significant for birth
      weight and birth date but not for natal litter size. Inadequately specified
      models greatly overestimated additive genetic variance and hence direct h2 (by a
      factor of up to 6.45 in the case of birth date). We conclude that failure to
      model heritable maternal variance can result in over- or under-estimation of the
      potential for traits to respond to selection, and advocate an increased effort to
      explicitly measure maternal genetic effects in evolutionary studies.

PMID- 15715848
TI  - Light quantity and quality induce shade-avoiding plasticity in a marine
      macroalga.
AB  - Light-induced plasticity in plant morphology is considered adaptive in
      terrestrial habitats that vary in light, but remains unexplored for marine
      habitats. This is despite similar modes of growth, development and photosynthetic
      equipment in terrestrial and marine photoautotrophs and similarly dynamic light
      environments. We tested whether manipulations of light quantity and quality
      induce morphological plasticity in the marine macroalga, Asparagopsis armata.
      Using multivariate analyses (principal components analyses and multivariate
      analyses of covariance), we show that correlated morphological traits underlie a
      fundamental growth strategy characterized by the production of phalanx and
      guerrilla phenotypes in environments that mimic light and shade respectively.
      This foraging response is not under simple genetic or environmental control, but
      influenced by interactions between genotype and environment. Evidence of
      plasticity and genetic variation in plasticity in a marine modular organism
      generates additional, testable hypotheses on the ecological consequences of
      variation in growth form that may further explain the evolution of plasticity.

PMID- 15715849
TI  - Rapid miocene-pliocene dispersal and evolution of Mediterranean rajid fauna as
      inferred by mitochondrial gene variation.
AB  - Rajidae (colloquially known as skates and rays) experienced multiple and parallel
      adaptive radiations allowing high species diversity and great differences of
      species composition between regional faunas. Nevertheless, they show considerable
      conservation of bio-ecological, morphological and reproductive traits. The
      evolutionary history and dispersal of North-east Atlantic and Mediterranean rajid
      fauna were investigated throughout the sequence analysis of the control region
      and 16S rDNA mitochondrial genes. Molecular estimates of divergence times
      indicated recent origin and rapid dispersal of the present species. Compared with
      the ancient origin of the family (Late Cretaceous), the present species diversity
      arose in a relatively narrow time-window (12 Myr) from Middle Miocene to Early
      Pleistocene, likely by speciation processes related to dramatic geological and
      climatic events in the Mediterranean. Nucleotide substitution rates and
      phylogenetic relationships indicated Mediterranean endemic skates derived from
      sister species with wider distribution during Late Pliocene-Pleistocene. Skate
      phylogeny and systematics obtained using mitochondrial gene variation were
      largely consistent with those based on morpho-anatomical data.

PMID- 15715850
TI  - Consequence of herbivory for the fitness cost of herbicide resistance:
      photosynthetic variation in the context of plant-herbivore interactions.
AB  - The cost of adaptations may depend on environmental conditions. We consider how
      the fitness cost of resistance to the herbicide triazine in Amaranthus hybridus
      interacts with folivory from the beetle Disonycha glabrata. Triazine-resistant
      (TR) genotypes suffer a fitness cost because of a pleiotropic reduction in the
      light reaction of photosynthesis, which in turn often leads to a reduction in
      photosynthetic rate. We found that the fitness cost of triazine resistance was
      360% greater in the presence than absence of D. glabrata. This resulted from
      multiple phenotypic trade-offs, with TR plants suffering greater herbivory and
      displaying a diminished tolerance of damage. Our work highlights the importance
      of incorporating appropriate ecological variation into the assessment of fitness
      trade-offs. The results of this study also illustrate the potential for
      herbivores to impose selection on photosynthetic variation, and for variation in
      resource acquisition to obscure fitness costs.

PMID- 15715852
TI  - Behavioural differences between individuals and two populations of stickleback
      (Gasterosteus aculeatus).
AB  - Behavioural syndromes are correlations between behaviours in different functional
      contexts. Behavioural syndromes are attracting the attention of evolutionary
      biologists because they mean that different behaviours might not be free to
      evolve independently of one another. In a landmark study, Huntingford (1976)
      showed that individual stickleback which were bold toward predators were also
      aggressive toward conspecifics and active in an unfamiliar environment. Here, I
      revisited the activity-aggression-boldness syndrome in stickleback and tested the
      hypothesis that correlations between behaviours might act as evolutionary
      constraints. I measured a suite of behaviours on wild-caught individuals and
      their offspring from two different populations and calculated heritabilities and
      genetic correlations between the different behaviours. I found that these
      behaviours were phenotypically and genetically correlated in one population but
      not another. On average, boldness and aggression were negatively related to each
      other across the populations. These results suggest that behavioural syndromes
      don't always act as evolutionary constraints.

PMID- 15715851
TI  - Sex and immunity in the yellow dung fly Scathophaga stercoraria.
AB  - The immune system is of increasing interest to evolutionary biologists. Immunity
      may trade-off against other fitness components, with recent work suggesting
      reproduction in particular impinges on immune defence. There may also be sex
      differences in the immune system. Additionally, while life history traits
      typically have low heritability, little is known about additive genetic variance
      of immunity. An insect's major defence against multicellular pathogens is to
      encapsulate the invader. Phenoloxidase (PO) is a key enzyme in the cascade
      resulting in the melanized capsule, and is often used to estimate resistance to
      an immune insult. We examined the effects of copulation, egg laying, sex and age
      on PO in Scathophaga stercoraria. We also measured the heritability of PO
      activity. The sexes differed in haemolymph PO activity and PO was significantly
      affected by age, but not by copulation or egg laying. There was significant
      heritable variation for haemolymph PO.

PMID- 15715853
TI  - Sperm competition and male ejaculate investment in Nauphoeta cinerea: effects of
      social environment during development.
AB  - Selective pressure arising from sperm competition has been predicted to influence
      evolutionary and behavioural adjustment of ejaculate investment, but also may
      influence developmental adjustment of ejaculate investment. Immature males able
      to target resources strategically based on the competitive environment they will
      experience when they become sexually mature should be at a selective advantage.
      In our study we investigated how the presence of potential competitors or mates
      affects ejaculate and testes investment during development in the cockroach
      Nauphoeta cinerea, a species where males control female remating via their
      ejaculate size (large spermatophores prevent females from remating and therefore
      function to avoid sperm competition for males) and females store sperm. Our aim
      was to determine whether the social environment influences developmental
      adjustment of ejaculate investment and the relative importance of ejaculate
      components with different functions; avoidance of or engagement in sperm
      competition. We conclude that the social environment can influence developmental
      and behavioural flexibility in specific ejaculate components that may function to
      avoid or engage in sperm competition.

PMID- 15715854
TI  - Rapid evolutionary change in a secondary sexual character linked to climatic
      change.
AB  - The ability of organisms to respond evolutionarily to rapid climatic change is
      poorly known. Secondary sexual characters show the potential for rapid
      evolutionary change, as evidenced by strong divergence among species and high
      evolvability. Here we show that the length of the outermost tail feathers of
      males of the socially monogamous barn swallow Hirundo rustica, feathers that
      provide a mating advantage to males, has increased by more than 1 standard
      deviation during the period from 1984 to 2003. Barn swallows from the Danish
      population studied here migrate through the Iberian Peninsula to South Africa in
      fall, and return along the same route in spring. Environmental conditions on the
      spring staging grounds in Algeria, as indexed by the Normalized Difference
      Vegetation Index, predicted tail length and change in tail length across
      generations. However, conditions in the winter quarters and at the breeding
      grounds did not predict change in tail length. Environmental conditions in
      Algeria in spring showed a temporal deterioration during the study period,
      associated with a reduction in annual survival rate of male barn swallows.
      Phenotypic plasticity in tail length of males, estimated as the increase in tail
      length from the age of 1 to 2 years, decreased during the course of the study.
      Estimates of directional selection differentials for male tail length with
      respect to mating success, breeding date, fecundity, survival and total selection
      showed temporal variation, with the intensity of breeding date selection,
      survival selection and total selection declining during the study. Response to
      selection as estimated from the product of heritability and total selection was
      very similar to the observed temporal change in tail length. These findings
      provide evidence of rapid micro-evolutionary change in a secondary sexual
      character during a very short time period, which is associated with a rapid
      change in environmental conditions.

PMID- 15715855
TI  - Antimicrobial activity of chlorhexidine diacetate and benzalkonium chloride
      against Pseudomonas aeruginosa and its response to biocide residues.
AB  - AIMS: The aims of this study were to evaluate the antimicrobial activity of
      chlorhexidine diacetate (CHX) and benzalkonium chloride (BZK) for strains of
      Pseudomonas aeruginosa exhibiting increased minimum inhibitory concentrations
      (MIC) for CHX, and to determine whether residues of chlorhexidine digluconate
      (CHG) and Hibiscrub (Hib, a formulation containing CHG) affect the susceptibility
      of P. aeruginosa to these biocides and a number of antibiotics. METHODS AND
      RESULTS: The bactericidal activity of CHX and BZK was evaluated for strains of P.
      aeruginosa exhibiting increased MIC for CHX with established suspension and
      surface disinfection tests. None of the strains of P. aeruginosa exhibiting
      raised MIC for CHX was less sensitive than the parent strain to CHX or BZK in
      either method. A test was designed to investigate the effects of dried CHG and
      Hib residues on P. aeruginosa cells. Exposure of P. aeruginosa to dried residues
      of CHG or Hib did not result in the organism becoming less sensitive to either
      biocide or a number of antibiotics. CONCLUSIONS: Pseudomonas aeruginosa strains
      with raised MIC to CHX were no less sensitive than the parent strain to CHX and
      BZK in bactericidal investigations. Exposure to dried residues of CHG and Hib did
      not render P. aeruginosa less sensitive to either of these agents or a number of
      antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: An increase in the MIC for a
      biocide in a micro-organism does not necessarily result in a failure of the
      biocide to effectively kill the organism. The residue that remains after the use
      of an antimicrobial agent can be at a far lower concentration than that initially
      applied and this study highlights the necessity for further investigations into
      the effect of residues, at low concentration, on bacterial populations and their
      role, if any, in the continued problem of antibiotic resistance.

PMID- 15715856
TI  - Molecular typing of epidemic and nonepidemic Vibrio cholerae isolates and
      differentiation of V. cholerae and V. mimicus isolates by PCR-single-strand
      conformation polymorphism analysis.
AB  - AIMS: To examine the utility of polymerase chain reaction (PCR)-single-strand
      conformation polymorphism (SSCP) analysis to differentiate epidemic and
      nonepidemic Vibrio cholerae isolates as well as to differentiate V. cholerae and
      Vibrio mimicus isolates. METHODS AND RESULTS: By both PCR-restriction fragment
      length polymorphism (RFLP) and PCR-SSCP analysis of groEL-I on chromosome 1 and
      groEL-II on chromosome 2, V. cholerae isolates gave distinct profiles compared
      with V. mimicus isolates. In addition, PCR-SSCP analysis of groEL-I and groEL-II
      could differentiate between V. cholerae epidemic and nonepidemic isolates.
      Interestingly, the relationships among strains based on groEL-I from chromosome 1
      and groEL-II from chromosome 2 were congruent with each other, highlighting the
      conserved evolutionary history of both chromosomes in this species. CONCLUSIONS:
      PCR-SSCP is a powerful typing technique, which has the ability to differentiate
      V. cholerae and V. mimicus isolates. The epidemic V. cholerae O1/O139 serogroup
      isolates represent a clonal complex distinct from non-O1/non-O139 isolates that
      can be identified by PCR-SSCP analysis. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study highlights the effectiveness of using reliable molecular typing
      methods and in particular PCR-SSCP, to identify genetic variation among V.
      cholerae and V. mimicus isolates.

PMID- 15715857
TI  - Farm disinfectants select for cyclohexane resistance, a marker of multiple
      antibiotic resistance, in Escherichia coli.
AB  - AIMS: The aim of this study was to determine if three classes of farm
      disinfectants were able to select for ciprofloxacin or cyclohexane tolerant
      [indicative of a multiple antibiotic resistance (MAR) phenotype] Escherichia coli
      and if cyclohexane-tolerant E. coli could be isolated from farms. METHODS AND
      RESULTS: Chicken slurry containing ca 1 : 99 ratio ciprofloxacin resistant :
      susceptible E. coli (10 different resistant strains examined) was treated for 24
      h with each of the disinfectants and examined for survival of resistant :
      susceptible strains. Ciprofloxacin-sensitive (n=5) and -resistant (n=5) E. coli
      were grown with sublethal concentrations of the disinfectants and then plated to
      agar containing ciprofloxacin or overlaid with cyclohexane. Escherichia coli
      (n=389) isolated from farms were tested for cyclohexane tolerance. Minimum
      inhibitory concentrations (MIC) were determined against representative isolates
      and mutants. The disinfectants did not select for the ciprofloxacin-resistant E.
      coli in poultry slurry but following growth with each of the three disinfectants,
      higher numbers (P < or = 0.023) of cyclohexane-tolerant E. coli were isolated and
      these had a MAR phenotype. Of the 389 farm E. coli tested, only one was
      cyclohexane tolerant. CONCLUSIONS: It is possible that in a farm environment, E.
      coli could be exposed to similar concentrations of the disinfectants that are
      selected for MAR type organisms under these laboratory conditions. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Data from this study suggest that cyclohexane-resistant
      E. coli are not common on farms, but in view of the ease of isolating them in the
      laboratory with farm disinfectants, further investigations on farms are
      warranted.

PMID- 15715858
TI  - Effect of the growth promoter avilamycin on emergence and persistence of
      antimicrobial resistance in enteric bacteria in the pig.
AB  - AIM: To assess the effect of the growth promoter avilamycin on emergence and
      persistence of resistance in enteric bacteria in the pig. METHODS AND RESULTS:
      Pigs (treated with avilamycin for 3 months and controls) were challenged with
      multi-resistant Salmonella Typhimurium DT104 and faecal counts were performed for
      enterococci, Escherichia coli, S. Typhimurium and Campylobacter (before, during
      and 5 weeks post-treatment). Representative isolates were tested for antibiotic
      resistance and for the presence of resistance genes. Avilamycin-resistant
      Enterococci faecalis (speciated by PCR) were isolated from the treated pigs and
      continued to be detected for the first week after treatment had ceased. The
      avilamycin-resistance gene was characterized by PCR as the emtA gene and
      speciation by PCR. MIC profiling confirmed that more than one strain of Ent.
      faecalis carried this gene. There was no evidence of increased antimicrobial
      resistance in the E. coli, Salmonella and Campylobacter populations, although
      there was a higher incidence of tetB positive E. coli in the treated pigs than
      the controls. CONCLUSION: Although avilamycin selects for resistance in the
      native enterococci population of the pig, no resistant isolates were detected
      beyond 1 week post-treatment. This suggests that resistant isolates were unable
      to persist once selective pressure was removed and were out-competed by the
      sensitive microflora. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data suggest the
      risk of resistant isolates becoming carcass contaminants and infecting humans
      could be minimized by introducing a withdrawal period after using avilamycin and
      prior to slaughter.

PMID- 15715859
TI  - Characterization of new O3:K6 strains and phylogenetically related strains of
      Vibrio parahaemolyticus isolated in Taiwan and other countries.
AB  - AIMS: We analysed the genetic divergence in the pandemic new O3:K6 and
      phylogenetically related (new O3:K6-like) strains and compare these two groups in
      terms of virulence and other biological traits. METHODS AND RESULTS: A total of
      160 new O3:K6, new O3:K6-like and other strains of Vibrio parahaemolyticus
      isolated in Taiwan and other countries were collected and their clonal
      relationships analysed using SfiI-pulsed-field gel electrophoresis. All of the
      new O3:K6 and new O3:K6-like strains were grouped in cluster I with five new
      patterns identified. A O6:K18 strain was identified as a new member of the new
      O3:K6-like strains in addition to O4:K68, O1:KUT and O1:K25 strains. All of the
      lipopolysaccharide preparations of the selected strains exhibited closely spaced
      quadruplet banding patterns with similar mobility. The two groups of strains
      exhibited 100% sequence identity in the internal sequences of the toxR and laf
      genes, and also displayed similar virulence properties as determined with a
      suckling mouse model. CONCLUSIONS: The new O3:K6 and new O3:K6-like strains were
      highly similar in virulence and in several other phenotypical and genotypical
      traits. SIGNIFICANCE AND IMPACT OF THE STUDY: This work demonstrated the spread
      and divergence of the pandemic and related clone of V. parahaemolyticus with
      similar virulence.

PMID- 15715860
TI  - Effect of environmental and physiological factors on the antibacterial activity
      of Curvularia haloperoxidase system against Escherichia coli.
AB  - AIMS: The aim of this study was to investigate the influence of environmental and
      physiological factors on the susceptibility of Escherichia coli to the Curvularia
      haloperoxidase system. METHODS AND RESULTS: The Curvularia haloperoxidase system
      is a novel enzyme system that produces reactive oxygen species which have an
      antimicrobial effect. Escherichia coli MG1655 was exposed to the Curvularia
      haloperoxidase system under different temperatures and NaCl concentrations and
      after exposure to different stress factors. Temperature clearly affected
      enzymatic activity with increasing antibacterial effect at increasing
      temperature. The presence of NaCl interfered with the enzyme system and in the
      presence of 1% NaCl, no antibacterial effect could be observed at pH 7. Cells
      grown at pH 8.0 were in one experiment more resistant than cells grown at pH 6.5,
      whereas cells grown in the presence of 2% NaCl were more susceptible to the
      Curvularia haloperoxidase system. CONCLUSIONS: Environmental and physiological
      factors can affect the antibacterial activity of the Curvularia haloperoxidase
      system. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrates a systematic
      approach in assessing the effect of environmental and physiological factors on
      microbial susceptibility to biocides. Such information is crucial for prediction
      of application as well as potential side-effects.

PMID- 15715861
TI  - Combined use of an immunomagnetic separation method and immunoblotting for the
      enumeration and isolation of Escherichia coli O157 in wastewaters.
AB  - AIMS: The detection of Escherichia coli O157:H7 in environmental samples is a
      human concern. The high persistence of this serotype in the environment suggests
      that contaminated animal wastewater could act as a potential reservoir.
      Nevertheless, the high levels of background microflora and cell damage because of
      environmental stress hamper the isolation of this pathogen without using
      enrichment methods. This study develops a method for the detection of E. coli and
      investigates its prevalence in animal and human wastewaters. METHODS AND RESULTS:
      Incubation of the sample for 1 h 30 min at 37 degrees C in peptone water
      supplemented with vancomycin and cefsulodin, enhanced the recovery of bacteria
      whilst ensuring that no growth occurred. Subsequently, a combination of
      immunomagnetic separation, cefixime-tellurite-sorbitol MacConkey (CT-SMAC)
      plating and immunoblotting with specific O157 antibodies allowed the detection,
      enumeration and isolation of E. coli O157 strains in human, swine and cattle
      wastewaters, which presented values of 0.2, 0.4, and 1.0 log10 ml(-1) units,
      respectively. Some of the isolates carried genes coding for Shiga toxins, intimin
      and enterohemolysin. CONCLUSIONS: Escherichia coli O157 is commonly present in
      animal and human wastewaters. The developed method reduced the high rate of false
      positives reported for other technical approaches. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The confirmation of serotype by specific immunomethods is necessary to
      prevent false-positive detection and incorrect enumeration.

PMID- 15715862
TI  - Metal ions modulate gene expression and accumulation of the mycotoxins aflatoxin
      and zearalenone.
AB  - AIMS: To determine the modulating action of some metal ions (Zn+2, Fe+2, Cu+2) on
      gene expression of enzymes related to fungal growth and accumulation of the
      mycotoxins aflatoxin and zearalenone. METHODS AND RESULTS: The effect of the
      metal ions, as single or mixed treatments, was observed in submerged cultures of
      toxigenic Aspergillus flavus or Fusarium graminearum, which produce the
      mycotoxins aflatoxin or zearalenone, respectively. The enzyme-linked
      immunosorbent assay results showed that the single metals Zn+2 or Cu+2 stimulated
      aflatoxin accumulation while Cu+2 or Fe+2 stimulated zearalenone in fungal
      cultures. Single Zn+2 treatment also affected conidial differentiation and
      pigmentation. A cDNA suppression subtractive library was also produced and
      followed by sequencing of potential metal treatment-specific clones, thus
      determining induced genes. The genes uncovered included enzymes and regulators of
      cell growth and division, including many genes with unknown functions were
      uncovered. A Northern blot analysis was used to verify the expression pattern of
      the corresponding genes under metal treatment. The metal ions enhanced the
      expression of alcohol dehydrogenase Adh1 homologue by up to 33-fold in A. flavus
      and ca fourfold in F. graminearum. Encoding homologues of a neutral amino acid
      permease, were also used in the Northern analysis. However, the expression of the
      permease was not significantly affected by metal ion treatments. CONCLUSIONS: The
      results showed a significant effect of metal ions on expression of gene related
      to fungal growth, development, conidiation and production of both aflatoxin and
      zearalenone. SIGNIFICANT AND IMPACT OF THE STUDY: At the molecular and cellular
      level, the significant effects of metal ions on fungal growth and development,
      conidiation, and production of both aflatoxin and zearalenone were demonstrated.

PMID- 15715863
TI  - Analysis of factors that influence the sensitivity of spores of Bacillus subtilis
      to DNA damaging chemicals.
AB  - AIMS: To elucidate factors influencing the sensitivity of Bacillus subtilis
      spores to DNA damaging chemicals. METHODS AND RESULTS: Wild-type spores of B.
      subtilis made at lower temperatures were more sensitive to the DNA damaging
      chemicals formaldehyde and nitrous acid than were spores made at higher
      temperatures, but this was not the case with the DNA alkylating agents
      ethylmethanesulphonate and methylmethanesulphonate. Spores lacking most DNA
      protective alpha/beta-type small, acid-soluble proteins (termed alpha-beta-
      spores) made at lower temperatures were also more sensitive to killing through
      DNA damage by hydrogen peroxide than were alpha-beta- spores made at higher
      temperatures. The spore coat, whose composition varies significantly with
      sporulation temperature, played only a minor role in spore resistance to these
      DNA damaging agents. Spores made at lower temperatures exhibited higher
      permeability to the methylamine and germinated more rapidly with the surfactant
      dodecylamine than did spores made at higher temperatures. Treatment of spores
      with the oxidizing agent cumene hydroperoxide sensitized the surviving spores to
      all these DNA damaging agents. The fatty acid composition of the inner membrane
      of spores made at different temperatures differed significantly, but levels of
      unsaturated fatty acids in the inner membrane did not influence spore resistance
      to DNA damaging agents or the sensitization to such agents by prior treatment
      with cumene hydroperoxide. CONCLUSIONS: The higher rates of methylamine
      permeation across the inner membrane of spores made at lower temperatures and the
      greater sensitivity of wild-type spores made at lower temperatures to
      formaldehyde and nitrous acid and of alpha-beta- spores made at lower
      temperatures to hydrogen peroxide, all agents that must pass through the spore's
      inner membrane to damage DNA in the spore core, suggest that the permeability of
      the inner membrane is a significant factor influencing spore sensitivity to these
      agents. The sensitization of spores to DNA damaging chemicals by pretreatment
      with an oxidizing agent, a treatment that increases the permeability of the
      spore's inner membrane, and the more rapid dodecylamine germination of spores
      made at lower temperatures are consistent with this suggestion. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The results in this communication provide new insight into
      the factors that influence the resistance of spores of Bacillus species to
      chemicals that kill spores by damaging spore DNA.

PMID- 15715864
TI  - The effect of thermal treatments on the viability and infectivity of
      Cryptosporidium parvum on beef surfaces.
AB  - AIMS: The aim of this research was to examine the effect of thermal treatments on
      the viability and infectivity of Cryptosporidium parvum oocysts attached to a
      beef surface. METHODS AND RESULTS: This study examined the effects of heat
      treatment (60 or 75 degrees C) on the viability of C. parvum oocysts inoculated
      onto the surface of beef muscle estimated by vital dye assay. The infectivity of
      the oocysts was assessed against monolayers of HCT-8 cells. At 60 degrees C
      viability of the oocysts decreased from 100% at T0 to 64.2% at T60. At 75 degrees
      C the viability of the oocysts decreased from 100% at T0 to 53.7% at T15 and
      finally to 11.2% at T60. Oocysts were rendered noninfective against monolayers of
      HCT-8 cells following treatments of 60 degrees C/45 s and 75 degrees C/20 s.
      CONCLUSION: The washing of carcasses with hot water and standard thermal
      treatments is sufficient to kill C. parvum on beef. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study found that relatively mild heat, currently used to
      decontaminate and heat treat beef carcasses and to cook meat products, is capable
      of inactivating C. parvum.

PMID- 15715865
TI  - Development and characterization of a simple perfused oral microcosm.
AB  - AIMS: To validate perfused, inline, filter-based fermentation systems (multiple
      Sorbarod devices, MSD) for their ability to maintain stable oral bacterial
      communities. MSD enable replicate (n=5) microcosm biofilms (BF) to be established
      and sampled, together with their perfusates (PA, cells in eluted medium). METHODS
      AND RESULTS: Fresh saliva from human volunteers was used to inoculate MSD,
      incubated in an anaerobic cabinet and perfused with artificial saliva at 7 ml h(
      1). BF within Sorbarod filters and cells eluted in the PA were analysed at 24-h
      intervals by differential bacteriological culture and checkerboard DNA-DNA
      hybridization (CKB, 40 oral species). Dynamic stability was apparent after 2-3
      days within both BF and PA as evidenced by culture, CKB data and pH measurements.
      BF harboured large numbers of anaerobic species and facultative anaerobes [ca 10
      11 log10 colony-forming units (CFU)/filter] comprising considerable numbers of
      streptococci and Gram-negative species. PA contained ca 9-10 log(10) CFU ml(-1)
      suggesting an apparent mean growth rate of 0.1 h(-1) for the BF, as a whole
      corresponding to a mean generation time of 10 h. CKB analysis revealed
      considerable bacterial diversity within the respective MSD. Inter-individual
      variations in the relative species abundance of inocula was broadly reproduced in
      the MSD (BF and PA), although considerable variation was apparent between
      triplicate models established using saliva from one saliva donor or from three
      individual donors. The dominance of Gram-negative species, indicated by culture
      was supported by CKB analysis (major species, Prevotella melaninogenica and
      Fusobacterium nucleatum). CONCLUSIONS: Data obtained from the various analytical
      approaches showed a high degree of congruence. The MSD enables the maintenance of
      complex, stable salivary microcosms and represents a simple, reproducible tool
      for modelling individual oral bacterial ecosystems. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study demonstrates the utility of the MSD for studying the micro
      ecology of the oral cavity.

PMID- 15715866
TI  - The bphC gene-encoded 2,3-dihydroxybiphenyl-1,2-dioxygenase is involved in
      complete degradation of dibenzofuran by the biphenyl-degrading bacterium
      Ralstonia sp. SBUG 290.
AB  - AIMS: Biphenyl-degrading bacteria are able to metabolize dibenzofuran via lateral
      dioxygenation and meta-cleavage of the dihydroxylated dibenzofuran produced. This
      degradation was considered to be incomplete because accumulation of a yellow
      orange ring-cleavage product was observed. In this study, we want to characterize
      the 1,2-dihydroxydibenzofuran cleaving enzyme which is involved in dibenzofuran
      degradation in the bacterium Ralstonia sp. SBUG 290. METHODS AND RESULTS: In this
      strain, complete degradation of dibenzofuran was observed after cultivation on
      biphenyl. The enzyme shows a wide substrate utilization spectrum, including 1,2
      dihydroxydibenzofuran, 2,3-dihydroxybiphenyl, 1,2-dihydroxynaphthalene, 3- and 4
      methylcatechol and catechol. MALDI-TOF analysis of the protein revealed a strong
      homology to the bphC gene products. We therefore cloned a 3.2 kb DNA fragment
      containing the bphC gene of Ralstonia sp. SBUG 290. The deduced amino acid
      sequence of bphC is identical to that of the corresponding gene in Pseudomonas
      sp. KKS102. The bphC gene was expressed in Escherichia coli and the meta-fission
      activity was detected using either 2,3-dihydroxybiphenyl or 1,2
      dihydroxydibenzofuran as substrate. CONCLUSIONS: These results demonstrate that
      complete degradation of dibenzofuran by biphenyl degraders can occur after
      initial oxidation steps catalysed by gene products encoded by the bph-operon. The
      ring fission of 1,2-dihydroxydibenzofuran is catalysed by BphC. Differences found
      in the metabolism of the ring fission product of dibenzofuran among biphenyl
      degrading bacteria are assumed to be caused by different substrate specificities
      of BphD. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows for the first
      time that the gene products of the bph-operon are involved in the mineralization
      of dibenzofuran in biphenyl degrading bacteria.

PMID- 15715867
TI  - Concentration and prevalence of Escherichia coli O157 in sheep faeces at pasture
      in Scotland.
AB  - AIMS: To study the presence, numbers and virulence profiles of Escherichia coli
      O157 in sheep faeces and validate the microbiological methods used to attain
      these data. METHODS AND RESULTS: Flock level prevalence was found to be 40% (six
      from 15) and 6.5% of faecal samples tested were found to be positive. Two farms
      gave samples defined as high shedding (>10(4) CFU g(-1)), one of which comprised
      91% positive samples with 13/33 at the high shedding level. CONCLUSIONS: These
      data confirmed that sheep are an important reservoir of E. coli O157.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Sheep play a significant role in the
      maintenance and dispersal of E. coli O157 in the farming environment and are an
      important source of human infection.

PMID- 15715868
TI  - Effect of nitrogen limitation and nature of the feed upon Oenococcus oeni
      metabolism and extracellular protein production.
AB  - AIMS: The aim of the study was to characterize the effect of various nitrogen
      sources on Oenococcus oeni growth, carbon source utilization, extracellular
      protease activity and extracellular proteins. More generally, the goal is to
      understand how nitrogen-based additives might act to enhance malolactic
      fermentation in wine. METHODS AND RESULTS: Five yeast extracts were used. As the
      amino acid and nitrogen analyses revealed, they were similar in global amino acid
      composition, except for arginine level. Nevertheless the ratio of amino acids
      between free/bound, and low/high molecular weight fractions were highly
      different. One of the yeast extracts led to a significant protease activity in
      the supernatant and to a poor final biomass of the IOB84.13 strain compared to
      the other ones. For the IOB84.13 strain specifically, arginine addition to the
      arginine poor yeast extract did not restore growth. 35S-methionine-labelled
      extracellular proteins were separated by SDS-PAGE. Signals were detected in all
      media early in the growth phase and were maintained during 48 h of culture.
      CONCLUSIONS: A significant protease activity was detected for O. oeni
      supernatants during growth under nitrogen limitation but only for certain
      nitrogen sources. Moreover, the activity was strain dependent. Peptides (0.5-10
      kDa) seemed to be more favourable for growth of wine bacteria than <0.5 kDa
      nitrogen sources. The extracellular protein signal patterns differed more greatly
      between the bacterial strains tested than between the nitrogen molecules in the
      medium. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study extensively
      considering the role of the nitrogen source composition and level upon O. oeni
      growth and metabolism.

PMID- 15715869
TI  - Antibacterial activity of lactic acid bacteria included in inoculants for silage
      and in silages treated with these inoculants.
AB  - AIMS: To determine antibacterial activity in lactic acid bacteria (LAB) silage
      inoculants and in wheat and corn silages which were treated with these
      inoculants. METHODS AND RESULTS: Wheat and two corn silages were prepared in 0.25
      l sealed glass jars. Inoculant treatments were prepared for each type of silage
      with each of 10 LAB silage inoculants at inoculation rate of 10(6) CFU g(-1).
      Untreated silages served as controls. Antibacterial activity was determined in
      the inoculants and in their respective silages with Micrococcus luteus and
      Pseudomonas aeruginosa. Antibacterial activity was detected in nine of the 10
      inoculants whereas such activity in the silages varied. Control silages did not
      have antibacterial activity. CONCLUSIONS: Many LAB silage inoculants have
      antibacterial activity and in some cases this activity is imparted on inoculated
      silages. SIGNIFICANCE AND IMPACT OF THE STUDY: This study was conducted as part
      of a broader research objective, which is to find out how LAB silage inoculants
      enhance ruminant performance. The results of this study indicate that LAB silage
      inoculants produce antibacterial activity, and therefore, have a potential to
      inhibit detrimental micro-organisms in the silage or in the rumen.

PMID- 15715870
TI  - Production of antimicrobial substances by Bacillus subtilis LFE-1, B. firmus HO-1
      and B. licheniformis T6-5 isolated from an oil reservoir in Brazil.
AB  - AIMS: Forty Bacillus strains isolated from a Brazilian oil reservoir were tested
      against each other to select strains producing antimicrobial substances (AMS).
      Three strains, Bacillus subtilis (LFE-1), Bacillus firmus (H2O-1) and Bacillus
      licheniformis (T6-5), were selected due to their ability to inhibit more than 65%
      of the Bacillus strains tested. These three strains were also investigated for
      their capability to inhibit sulphate-reducing bacteria (SRB). Furthermore,
      physiological and biochemical characteristics of the antimicrobial compounds
      produced by the selected strains were determined. METHODS AND RESULTS: Among the
      forty strains tested, 36 (90%) strains were able to inhibit at least one Bacillus
      strain used as indicator in plate assays and three of them (LFE-1, T6-5 and H2O
      1) were able to inhibit 65, 70 and 97.5% of the 40 strains studied here
      respectively. Clear zones of inhibition were observed when H2O-1 was tested
      against SRB-containing consortium T6-lab and Desulfovibrio alaskensis strain
      NCIMB 13491, while strain T6-5 was able to inhibit only the D. alaskensis strain.
      The three substances showed to be insensitive to different enzymes and chemicals,
      were heat stable and the substances produced by strains T6-5 and H2O-1 were
      active over a wide pH range. CONCLUSIONS: Three different AMS produced by
      Bacillus strains from an oil reservoir, two of them with activity against SRB,
      are presented here. SIGNIFICANCE AND IMPACT OF THE STUDY: The preliminary
      characterization of these AMS points to their potential use as biocides in the
      petroleum industry for controlling problems associated with SRB.

PMID- 15715871
TI  - A versatile system for the expression of nonmodified bacteriocins in Escherichia
      coli.
AB  - AIMS: To develop a method and plasmid vectors suitable for expression of class II
      bacteriocins from Escherichia coli. METHODS AND RESULTS: The expression vector
      pSuV1 was constructed by inserting the PelB secretion signal coding sequence and
      a number of restriction endonuclease sites for cloning, into pTYB1. Codon
      optimized genes encoding the active mature region of each bacteriocin were
      constructed and inserted into pSuV1. Transfer of these constructs to a host
      expressing T7 RNA polymerase allowed for expression of secreted mature or fusion
      forms of the bacteriocins. Generation of the fusion, to the adjacent intein
      chitin-binding domain gene, was achieved by removal of a small intervening BseRI
      fragment. The bacteriocins BacR1, divercin V41, enterocin P, pediocin PA-1 and
      piscicolin 126 were expressed from this system. For piscicolin 126, expression
      levels of 200 microg l(-1) in the mature form and 1100 microg l(-1) when cleaved
      from the fusion partner were achieved. All expressed bacteriocins displayed
      antimicrobial activity. CONCLUSIONS: Several class II bacteriocins have been
      expressed in E. coli using purpose designed plasmid vectors described here.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This method provides a common expression
      system capable of producing a range of different class II bacteriocins. It allows
      researchers to study class II bacteriocins without access to the original
      producer strain, the native bacteriocin gene, or highly specific heterologous
      producing strains. Resulting expression levels are as high or higher than those
      previously reported for related bacteriocins.

PMID- 15715872
TI  - Ochratoxin A producing Penicillium verrucosum isolates from cereals reveal large
      AFLP fingerprinting variability.
AB  - AIMS: To examine if molecular amplified fragment length polymorphism (AFLP)
      fingerprinting of the only ochratoxin A-producing species in European cereals,
      Penicillium verrucosum, can be used as a method in hazard analysis using critical
      control points (HACCP). METHODS AND RESULTS: A total of 321 isolates of P.
      verrucosum were isolated from ochratoxin A-contaminated cereals from Denmark
      (oats), UK (wheat and barley) and Sweden (wheat). Of these, 236 produced
      ochratoxin A as determined by thin layer chromatography; 185 ochratoxin A
      producing isolates were selected for AFLP fingerprinting. A total of 138 isolates
      had unique AFLP patterns, whereas 52 isolates could be allocated to small groups
      containing from two to four isolates with similar AFLP patterns. A total of 155
      clones were found among the 185 P. verrucosum isolates, thus 84% of the isolates
      may represent different genets of P. verrucosum. As the few isolates that were
      grouped often came from the same farm, and those groups that contained AFLP
      identical isolates from different countries were morphotypically different. On
      single farms up to 35 clones were found. The few groups of ramets from the same
      genet indicated that a HACCP approach based on clones may require a very large
      number of AFLP analysis to work in practice, we recommend basing the HACCP
      approach on the actual species P. verrucosum. A more detailed characterization
      should rather be based on the profile of species present at different control
      points, or analysis of the mycotoxins ochratoxin A and citrinin in the isolates.
      Examination of 86 isolates with HPLC and diode array detection of P. verrucosum
      showed that 66% produced ochratoxin A, 87% produced citrinin, 92% produced
      verrucin and 100% produced verrucolone. CONCLUSIONS: Among 184 ochratoxin A
      producing Penicillium verrucosum, 155 clonal lineages were indicated by AFLP
      fingerprinting, indicating a high genetical diversity, yet the species P.
      verrucosum is phenotypically distinct and valid. SIGNIFICANCE AND IMPACT OF THE
      STUDY: AFLP fingerprinting of Penicillium verrucosum indicates that genetic
      recombination takes place in this fungus.

PMID- 15715873
TI  - Regulation of CO on heterocyst differentiation and nitrate uptake in the
      cyanobacterium Anabaena sp. PCC 7120.
AB  - AIMS: The aim of the present investigation was to study the effects of different
      inorganic carbon and nitrogen sources on nitrate uptake and heterocyst
      differentiation in the culture of cyanobacterium Anabaena sp. PCC 7120. METHODS
      AND RESULTS: Anabaena was cultivated in media BG11 containing combined nitrogen
      and supplementary NaHCO3 or CO2. Cell growth, heterocyst differentiation, nitrate
      reductase (NR, EC 1.7.7.2), glucose-6-phosphate dehydrogenase (G6PDH, EC
      1.1.1.49) and NO uptake were analysed. The cells cultivated in BG11(0) medium
      with aeration were taken as reference. Experimental results showed that the
      differentiation frequency of heterocysts when the cells were cultivated with
      elevated CO2 was higher than that of the cells grown with air or bicarbonate.
      Heterocysts appeared unexpectedly when CO2 was introduced into the medium
      containing nitrate. However, no heterocysts emerged when CO2 was added to medium
      containing NH or urea, or when NaHCO3 was supplied to the medium with nitrate.
      Both nitrate uptake rate and nitrate reduction enzyme activity were depressed by
      the supplement of CO2 to the culture. The activity of G6PDH was enhanced with the
      increase in heterocyst differentiation frequency. CONCLUSION: CO2 might compete
      with NO for energy and electrons in the uptake process and CO2 appears favoured.
      This led to a high intracellular C/N ratio and a relative N limitation. So the
      process of heterocyst differentiation was activated to supplement nitrogen
      uptake. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided an attractive
      possibility to form more heterocysts by rapid growth of Anabaena cells cultivated
      in the medium containing nitrate in order to increase nitrogen fixation and
      hydrogen production.

PMID- 15715874
TI  - The diversity of Escherichia coli serotypes and biotypes in cattle faeces.
AB  - AIM: To study the diversity of commensal Escherichia coli populations shed in
      faeces of cattle fed on different diets. METHODS AND RESULTS: Thirty Brahman
      cross steers were initially fed a high grain (80%) diet and then randomly
      allocated into three dietary treatment groups, fed 80% grain, roughage, or
      roughage + 50% molasses. Up to eight different E. coli isolates were selected
      from primary isolation plates of faecal samples from each animal. Fifty-two
      distinct serotypes, including nine different VTEC strains, were identified from a
      total of 474 E. coli isolates. Cattle fed a roughage + molasses diet had greater
      serotype diversity (30 serotypes identified) than cattle fed roughage or grain
      (21 and 17 serotypes identified respectively). Cluster analysis showed that
      serotypes isolated from cattle fed roughage and roughage + molasses diets were
      more closely associated than serotypes isolated from cattle fed grain. Resistance
      to one or more of 11 antimicrobial agents was detected among isolates from 20
      different serotypes. Whilst only 2.3% of E. coli isolates produced
      enterohaemolysin, 25% were found to produce alpha-haemolysin. CONCLUSIONS:
      Diverse non-VTEC populations of E. coli serotypes are shed in cattle faeces and
      diet may affect population diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study provides new information on the serotype diversity and phenotypic traits of
      predominant E. coli populations in cattle faeces, which could be sources of
      environmental contamination.

PMID- 15715875
TI  - Development of a semi-nested PCR based method for sensitive detection of
      tumorigenic Agrobacterium in soil.
AB  - AIMS: To develop a specific, sensitive and rapid PCR-based method for detection
      of tumorigenic Agrobacterium in soil. METHODS AND RESULTS: Three newly designed
      primers complementary to tms2 gene amplified DNA of only the tumor-inducing
      agrobacteria of 113 strains tested, resulting in 617 bp and 458 bp products in
      the first and second rounds of semi-nested PCR respectively. As optimized method
      of pre-incubation of soil suspensions on selective medium, DNA isolation and two
      round semi-nested PCR enabled detection of 1-2 bacterial cells in 1 g of soil.
      Using this method tumour-inducing Agrobacterium was detected in 67 of 69 samples
      of naturally infested soil originating from the field, where plants with crown
      gall symptoms occurred. The pathogen was detected only in two samples of 15
      tested, collected from a nursery where crown gall symptoms were not observed.
      CONCLUSIONS: The semi-nested PCR-based method allowed for sensitive and rapid
      detection of tumorigenic agrobacteria in soil. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The method is proposed for testing of soil in fields intended for nursery
      production of fruit trees, roses or other plants susceptible to crown gall, as
      well as a tool for ecological studies.

PMID- 15715876
TI  - Microbial content of commercial South African high-moisture dried fruits.
AB  - AIM: The aim was to evaluate commercially available South African high-moisture
      dried fruits (HMDF) for the microbial, moisture and SO2 contents, as well as aw
      and pH. METHODS AND RESULTS: The microbial content of commercially available HMDF
      was evaluated using nine different growth media. The moisture content, aw) SO2
      and pH of each product were determined using standard analytical methods. It was
      found that the highest total aerobic counts were generated from high-moisture
      dried (HMD) prunes and raisins. The most frequent spoilers were members of the
      genus Bacillus. Fungal counts were also very high in the apricot products,
      exceeding the limit of 1000 CFU g(-1) as set by HMDF producers. Members of the
      genus Staphylococcus were found in the HMD raisins and Salmonella and thermoduric
      organisms were isolated from the HMD prunes. CONCLUSIONS: The microbial levels of
      South African HMDF were within the limits set, with the exception of apricots.
      SIGNIFICANCE AND IMPACT OF STUDY: The study shows the presence of Salmonella,
      Staphylococcus and Clostridium in South African HMDF. The presence of thermoduric
      organisms indicated that the current pasteurization process is not adequate and
      that the addition of preservatives would be an additional method to ensure safety
      and quality.

PMID- 15715877
TI  - Identification of Meiothermus as the dominant genus in a storage system for spent
      nuclear fuel.
AB  - AIMS: To characterize the biofilms in an interim wet storage system (CLAB) for
      spent nuclear fuel. METHODS AND RESULTS: Planktonic cells and biofilms were
      analysed with fluorescence microscopy, and scanning and transmission electron
      microscopy. The organisms in the biofilms were filamentous, consisting of sheaths
      with series of rod-shaped cells in them. Planktonic cell populations ranged
      between 1.4 x 10(3) and 5.2 x 10(3) ml(-1), correlated with the system
      configuration, and was inversely correlated with total organic carbon (TOC)
      levels. Analysis of 16S rDNA indicated that a potentially novel Meiothermus sp.
      was dominant in the CLAB biofilms. A Meiothermus-specific probe was designed, and
      statistical analysis of fluorescence in situ hybridization results confirmed that
      Meiothermus sp. composed up to 98% of the biofilm. The low TOC levels (2-55
      microg l(-1)) in the system combined with elevated water temperatures (ca 36
      degrees C) mimic the natural environments of Meiothermus sp. as well as the
      recommended conditions for isolating Meiothermus sp., thus supporting the results
      of the 16S rDNA analysis. CONCLUSIONS: A possibly novel Meiothermus sp. is the
      predominant genus found in the CLAB biofilms. SIGNIFICANCE AND IMPACT OF THE
      STUDY: TOC levels are often kept low to protect industrial systems from
      biofouling. However, the present study shows that, rather than protecting
      industrial systems against biofouling per se, maintaining low TOC levels might
      still result in biofilms, dominated by new, unknown bacterial species.

PMID- 15715878
TI  - Studies of steam decontamination of beef inoculated with Escherichia coli O157:H7
      and its effect on subsequent storage.
AB  - AIM: This study was carried out to determine the survival of Escherichia coli
      O157:H7 and subsequent shelf life of beef subjected to subatmospheric steam at
      differing temperatures. METHODS AND RESULTS: A specifically built, laboratory
      scale decontamination apparatus was used in decontamination trials to examine the
      effect of condensing steam at differing subatmospheric pressures on the survival
      of E. coli O157:H7 on meat. Beef slices were inoculated with a nontoxigenic E.
      coli O157:H7 strain and subjected to condensing steam at temperatures of 55, 65
      and 75 degrees C. Following treatment, the decontaminated meat was packaged and
      stored in air or under vacuum at temperatures of 10 or 0 degrees C for up to 42
      days. Microbiological analysis of the decontaminated and a control product (not
      subjected to any heat treatment) was carried out at regular intervals over the
      storage time of the product. Overall, significant reductions (ca 1.5 log(10) CFU
      cm(-2)) in pathogen numbers were observed at a steam treatment temperature of 75
      degrees C, however, postprocess storage conditions were important in ensuring no
      re-growth of the pathogen and this was best achieved by storage under vacuum at 0
      degrees C. CONCLUSIONS: Steam had a significant impact in reducing E. coli
      O157:H7 populations, but storage conditions post-treatment were important for
      ensuring inhibition of the pathogen. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study indicated that subatmospheric steam could have significant application in
      the decontamination of meat primals postfabrication, immediately prior to
      packaging thus ensuring a safer product for consumers.

PMID- 15715880
TI  - Development of an asporogenic Bacillus licheniformis for the production of
      keratinase.
AB  - AIMS: Bacillus licheniformis PWD-1 is a keratin-degrading, spore-forming
      bacterium isolated from a poultry waste digester. A sporulation-deficient mutant
      of B. licheniformis PWD-1, named B. licheniformis WBG, was developed and
      characterized. METHODS AND RESULTS: The mutation was generated using the splicing
      by overlap extension PCR method (Gene SOEing) to create 256 bp deletion in the
      spoIIAC gene, which encodes an essential sporulation-specific sigma factor. In
      vivo gene replacement was accomplished with the use of a temperature-sensitive
      plasmid that is able to integrate and excise the nucleotide fragment 256 bp from
      the B. licheniformis chromosome. PCR analysis and DNA sequencing confirmed the
      spoIIAC gene deletion. Heat-treatment assays and electron microscopy verified the
      absence of spores. CONCLUSIONS: This asporogenic strain is able to express normal
      levels of keratinase when compared with its wild-type host. SIGNIFICANCE AND
      IMPACT OF THE STUDY: In this study, a method of constructing a stable sporulation
      defective strain was developed. It can be potentially useful as a tool to
      generate asporogenic strains of Bacillus that retain their industrial
      capabilities for production of exoproteases and other exozymes.

PMID- 15715879
TI  - Microbiological, biochemical and sensory assessment of mussels (Mytilus
      galloprovincialis) stored under modified atmosphere packaging.
AB  - AIMS: To determine the microbiological, biochemical and sensory changes of
      mussels during storage under aerobic, vacuum packaging (VP) and modified
      atmosphere packaging (MAP) conditions at 4 degrees C, and to determine shelf-life
      of mussels under the same packaging conditions using the above assessment
      parameters. METHODS AND RESULTS: Aqua-cultured mussels (Mytilus
      galloprovincialis) were obtained from a local culture farm, packaged aerobically
      under VP and MAP (50%/50% CO2/N2: M1, 80%/20% CO2/N2: M2, 40%/30%/30% CO2/N2/O2:
      M3), and stored at 4 degrees C. Quality evaluation was carried out using
      microbiological, chemical and sensory analyses. Microbiological results revealed
      that the M2 and VP delayed microbial growth compared with that of air-packaged
      samples. The effect was more pronounced for total viable count (TVC), Pseudomonas
      spp., lactic acid bacteria (LAB) and H2S-producing bacteria. TVC was reduced by
      0.9-1.0, Pseudomonas spp. by 0.7-0.8, LAB by 1.0-2.2, H2S-producing bacteria by
      0.7-1.2. Enterobacteriaceae were not significantly affected by MAP conditions. Of
      the chemical indices determined, the total volatile basic nitrogen and
      trimethylamine nitrogen values remained lower than the proposed acceptability
      limits of 35 mg N 100 g(-1) and 12 mg N 100 g(-1), respectively, after 15 days of
      storage. Both the VP and air-packaged mussel samples exceeded these limits. The
      thiobarbituric acid value of all MAP and VP mussels remained lower than the
      proposed acceptability limit of 1 mg malondialdehyde kg(-1). The air-packaged
      samples exceeded this limit. All samples retained desirable sensory
      characteristics during the first 8 days of storage. CONCLUSIONS: Based on odour
      and taste evaluation, the M1 and M3 samples remained acceptable until ca day 11
      12, the M2 samples remained acceptable until ca day 14-15 days while the VP and
      air-packaged mussel samples remained acceptable until ca days 10-11 and 8-9 of
      storage respectively. Based primarily on sensory, but also on biochemical and
      microbiological parameters determined, M2 gas mixture was the most effective for
      mussel preservation achieving a shelf-life of ca 14-15 days. SIGNIFICANCE AND
      IMPACT OF THE STUDY: MAP (M2) can be used to increase the shelf-life of
      refrigerated mussels. A shelf-life extension of refrigerated mussels by ca 5-6
      days under MAP may be obtained.

PMID- 15715881
TI  - Occurrence of Helicobacter pylori DNA in the coastal environment of southern
      Italy (Straits of Messina).
AB  - AIMS: The occurrence of Helicobacter pylori in the coastal zone of the Straits of
      Messina (Italy) as free-living and associated with plankton was studied. METHODS
      AND RESULTS: Monthly sampling of seawater and plankton was carried out from April
      2002 to March, 2003. All environmental samples analysed by cultural method, did
      not show the presence of H. pylori. The DNA extracted from all environmental
      samples was tested by PCR by using primers for H. pylori 16S rRNA, ureA and cagA.
      16S rRNA PCR yielded amplified products of 522-bp in 15 of 36 (41.7%) of the
      environmental samples. By using the ureA primers to amplify the urea signal
      sequences, the predicted PCR products of 491-bp were obtained from eight (22.2%)
      of 36 environmental samples. PCR with cagA primers yielded amplified products of
      349-bp in DNA extracted of seven of 36 (19.4%) of the environmental samples. When
      16S rRNA, ureA and cagA amplified gene sequences were aligned with H. pylori
      26695 and J99 genome sequences, we obtained a percentage of alignment over 90%.
      CONCLUSIONS: The detection of H. pylori genes in marine samples allows us to
      consider the marine environment a possible reservoir for this pathogenic
      bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: The direct detection of H.
      pylori genes may be relevant in order to consider the marine environment as
      significant reservoir for this bacterium.

PMID- 15715882
TI  - Effect of the pH of growth on the survival of Lactobacillus delbrueckii subsp.
      bulgaricus to stress conditions during spray-drying.
AB  - AIMS: The aim of this study was to optimize survival of Lactobacillus delbrueckii
      subsp. bulgaricus during spray-drying and subsequent storage through optimizing
      the pH of growth conditions. METHODS AND RESULTS: Cell concentrates previously
      grown without or with pH controlled were spray-dried and stored at 20 degrees C
      and heat treated at 57 degrees C. Cells grown under noncontrolled pH were more
      resistant to both drying and heating than cells grown under controlled pH but no
      significant differences were observed during storage. The intracellular proteins
      profile of cells grown under both conditions was studied by two-dimensional SDS
      polyacrylamide gel electrophoresis. Eight proteins were identified using
      automated mass spectrometry (MS) and tandem mass spectrometry (MS/MS) data
      acquisition. Of the identified proteins, only cochaperonin GroES corresponded to
      a known heat shock protein (HSP). The other proteins identified are proteins
      involved in glycolysis. For cells grown under noncontrolled pH the expression of
      the Hsp70, GroES and GroEL, measured by Western blotting, was enhanced.
      CONCLUSIONS: The higher resistance of cells grown under noncontrolled pH
      correlates with the enhanced production of heat shock proteins. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Growth of L. bulgaricus under controlled pH (commonly used
      by the starter cultures production industry) results in cells more sensitive to
      stresses frequently encountered by the cells during starter cultures
      preparation/storage/utilization.

PMID- 15715883
TI  - Genetic characterization of the yeast Pichia anomala (strain K), an antagonist of
      postharvest diseases of apple.
AB  - AIMS: To obtain information about the genomic organization of Pichia anomala
      (strain K) and about its genomic diversity at species and intraspecies level.
      METHODS AND RESULTS: The PFGE karyotype of strain K was composed of four bands
      ranging in size from 1.1 to 3.2 Mb. The number of chromosomes was estimated at
      six since bands 2 and 3 seemed to result from the comigration of two chromosomes
      with similar size. A comparison of strain K and Hansenulawingeii migration
      profiles led to the estimate of K strain genome size at 11.7 Mb. Comparison with
      isogenic strains, resulting from the sporulation of strain K, highlighted some
      major karyotypic differences. Two segregants (KH6 and KH7) showed supernumerary
      chromosomes and one (KH9) displayed chromosomal length polymorphism. This genomic
      instability was confirmed by molecular hybridization with four probes, consisting
      of URA3, LEU2, PAEXG1 and PAEXG2 genes of P. anomala. URA3 and LEU2 probes showed
      second hybridization signals on supernumerary chromosomes of strain KH7 and on
      chromosome 6 of strain K for LEU2 only. Karyotypic comparison of seven non
      isogenic P. anomala strains revealed chromosomal length polymorphism, a sign of
      intraspecies variation. CONCLUSIONS: This work has supplied information about
      genome size and chromosome number of strain K of P. anomala. The strain seems to
      be aneuploid because of the presence of supernumerary chromosomes and additional
      hybridization signals for URA3 and LEU2 probes in the chromosomal profile of some
      segregants. The work also highlighted genomic diversity within the P. anomala
      species. SIGNIFICANCE AND IMPACT OF THE STUDY: Results obtained here increase
      information about the aneuploidy of P. anomala (strain K). Information about the
      genomic diversity of the segregants will be of great interest for further studies
      on strain K mode of action. The genome size and chromosomal profile of P. anomala
      presented here are different from the results obtained elsewhere for Hansenula
      anomala, while Hansenula is included as a synonym of Pichia. This warrants
      further studies to investigate this taxonomic relationship.

PMID- 15715884
TI  - Homocysteine concentrations in patients with diabetes mellitus--relationship to
      microvascular and macrovascular disease.

PMID- 15715885
TI  - Genetics of type 2 diabetes mellitus: status and perspectives.
AB  - Throughout the last decade, molecular genetic studies of non-autoimmune diabetes
      mellitus have contributed significantly to our present understanding of this
      disease's complex aetiopathogenesis. Monogenic forms of diabetes (maturity-onset
      diabetes of the young, MODY) have been identified and classified into MODY1-6
      according to the mutated genes that by being expressed in the pancreatic beta
      cells confirm at the molecular level the clinical presentation of MODY as a
      predominantly insulin secretory deficient form of diabetes mellitus. Genomewide
      linkage studies of presumed polygenic type 2 diabetic populations indicate that
      loci on chromosomes 1q, 5q, 8p, 10q, 12q and 20q contain susceptibility genes.
      Yet, so far, the only susceptibility gene, calpain-10 (CAPN10), which has been
      identified using genomewide linkage studies, is located on chromosome 2q37.
      Mutation analyses of selected 'candidate' susceptibility genes in various
      populations have also identified the widespread Pro12Ala variant of the
      peroxisome proliferator-activated receptor-gamma and the common Glu23Lys variant
      of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11). These variants may
      contribute significantly to the risk type 2 diabetes conferring insulin
      resistance of liver, muscle and fat (Pro12Ala) and a relative insulin secretory
      deficiency (Glu23Lys). It is likely that, in the near future, the recent more
      detailed knowledge of the human genome and insights into its haploblocks together
      with the developments of high-throughput and cheap genotyping will facilitate the
      discovery of many more type 2 diabetes gene variants in study materials, which
      are statistically powered and phenotypically well characterized. The results of
      these efforts are likely to be the platform for major progress in the development
      of personalized antidiabetic drugs with higher efficacy and few side effects.

PMID- 15715886
TI  - QT dispersion in type 2 diabetic patients with altered diurnal blood pressure
      rhythm.
AB  - BACKGROUND: QT dispersion (QTd) is a good prognostic marker in type 2 diabetic
      patients without previous cardiovascular disease. Diabetic patients with an
      attenuated decline in nocturnal blood pressure (non-dippers) have been shown to
      have increased risk of diabetic complications, vascular events and mortality.
      AIM: The aim of this study was to evaluate the relationship between diurnal blood
      pressure rhythm, QTd and microvascular complications in type 2 diabetic patients.
      METHODS: Cardiovascular autonomic function tests, 24-h ambulatory blood pressure
      monitoring and urinary albumin excretion measurements were performed in healthy
      controls (n = 25), normoalbuminuric (n = 34) and microalbuminuric (n = 23) type 2
      diabetic patients. QTd was assessed manually from 12-lead surface
      electrocardiograms. RESULTS: Compared with the controls, both normoalbuminuric
      and microalbuminuric diabetic patients had increased QTd (59.11 +/- 15.86; 60.27
      +/- 17.95 vs. 40.48 +/- 10.92, p < 0.001 and p < 0.001, respectively). Similarly,
      diabetic patients had increased QTd regardless of the presence of autonomic
      neuropathy. On the other hand, non-dipper diabetic patients had increased QTd
      compared with the controls and dipper diabetic patients (69.73 +/- 14.50 vs.
      40.48 +/- 10.92; 47.84 +/- 9.62 ms, p < 0.001). There was a negative correlation
      between QTd and diurnal diastolic blood pressure change (r = -0.48, p < 0.0005).
      CONCLUSION: Patients with type 2 diabetes mellitus were found to have increased
      QT dispersion irrespective of the presence of diabetic autonomic neuropathy.
      However, QT dispersion in dipper diabetic patients was similar to the controls.
      This finding might point out that attenuated decline of nocturnal blood pressure
      could be a more sensitive marker for autonomic neuropathy.

PMID- 15715887
TI  - Inverse relationship between cord blood adiponectin concentrations and the number
      of cigarettes smoked during pregnancy.
AB  - BACKGROUND: Maternal smoking is linked with several neonatal metabolic disorders.
      Adiponectin is an adipose-specific hormone with anti-inflammatory and
      antiatherogenic properties. AIM: The aim of this study was to evaluate the effect
      of maternal smoking on cord blood adiponectin concentrations. METHODS: We
      evaluate the effect of maternal smoking on cord blood adiponectin concentrations
      comparing 14 full-term and seven preterm newborns born to mothers who smoked
      during pregnancy with 77 full-term and 10 preterm neonates born to non-smokers
      mothers. RESULTS: Maternal smoking during pregnancy was significantly associated
      with decreased adiponectin levels of preterm newborns (p < 0.05). CONCLUSIONS:
      Our findings also reveal a significant relationship between the reported number
      of cigarettes smoked during pregnancy and cord blood adiponectin concentrations
      (p = 0.01), suggesting that this association could have a causal relationship.

PMID- 15715888
TI  - An algorithm for the treatment of type 2 diabetes in Latin America.
AB  - Diabetes is a principal and growing health concern in Latin America, accounting
      for significant mortality and morbidities. Large, randomized, prospective trials
      of various interventional therapies in patients with both type 1 and type 2
      diabetes have demonstrated that reductions in hyperglycaemia and management of
      diabetes-related risk factors can significantly reduce the micro- and
      macrovascular complications of diabetes. Therefore, patients with type 2 diabetes
      will benefit from more aggressive treatment regimens to help decrease the
      occurrence and rate of progression of diabetic complications. Given the many
      complexities of diabetes management, it is often difficult for general practice
      physicians to stay abreast of emerging treatment strategies and therapies. Owing
      to the high prevalence of type 2 diabetes in Latin America, the majority of
      patients with diabetes are treated by generalists rather than specialists. This
      article was intended to assist physicians and other healthcare professionals in
      developing and using effective treatment strategies to stem the growing epidemic
      of diabetes and its complications in Latin America.

PMID- 15715889
TI  - Comparison of pioglitazone with other antidiabetic drugs for associated incidence
      of liver failure: no evidence of increased risk of liver failure with
      pioglitazone.
AB  - AIM: The aim of this study was to assess the incidence of liver failure in
      association with antidiabetic treatment using pioglitazone vs. other oral
      antidiabetic medications. METHODS: The study was a retrospective analysis of
      claim data from the PharMetrics Patient-Centric Database that had over 1.12
      million enrollees with type 2 diabetes. All patients, > or =18 years of age with
      type 2 diabetes, who had initiated treatment either with a thiazolidinedione
      (pioglitazone and rosiglitazone), sulfonylurea or metformin were identified and
      matched on the basis of propensity scores, which served as a proxy for severity
      of disease. The primary measure of interest was the incidence of liver failure or
      hepatitis post-index date. In addition to unadjusted comparisons, Cox
      proportional hazard models were employed to estimate the risk of developing liver
      failure or hepatitis. RESULTS: There was no significant difference in the 1- and
      2-year incidence rates of liver failure or hepatitis (primary and secondary
      diagnoses) between the pioglitazone monotherapy group and the respective
      comparator groups. In Cox proportional hazard models controlling for age, pre
      index total healthcare costs, Charlson comorbidity index, procedures and a
      hospitalization or Emergency room (ER) visit for pre-index hyperglycaemia, and
      pioglitazone were not associated with an increased risk of liver failure or
      hepatitis, compared to all other defined groups. Furthermore, no primary or
      secondary diagnosis of liver failure was reported in the pioglitazone group
      during the follow-up period. CONCLUSIONS: Results of retrospective data analysis
      demonstrate no evidence of increased risk of liver failure or hepatitis for
      patients initiating therapy on pioglitazone, compared to other oral antidiabetic
      agents. Pioglitazone therapy was not associated with an increased risk of liver
      failure at 2 years relative to other oral antidiabetic therapies.

PMID- 15715891
TI  - Weight loss-associated changes in acute effects of nateglinide on insulin
      secretion after glucose loading: results of glucose loading on 2 consecutive
      days.
AB  - AIM: The aim of this study was to investigate the influence of changes in insulin
      resistance and early insulin secretion on the insulin secretagogic effects of
      nateglinide. METHODS: Oral glucose tolerance testing (OGTT, 75 g) was performed
      in obese patients before and after weight loss on 2 consecutive days (first day
      OGTT without nateglinide, second day OGTT with nateglinide), to compare any
      weight loss associated changes in the nateglinide-induced insulin response to
      glucose loading. RESULTS: Reductions in visceral fat, liver fat, skeletal muscle
      fat and homeostasis model assessment (HOMA)-R due to weight loss were associated
      with increased Delta insulin 30 min/Delta glucose 30 min (DeltaI30/DeltaG30), and
      reduced area under the curve (AUC) for plasma glucose as seen in OGTT results.
      Results from OGTT showed that nateglinide administration was associated with
      reductions in plasma glucose AUC, both before and after weight loss. Before
      weight loss, although there was a significant elevation of DeltaI30/DeltaG30
      associated with nateglinide treatment, no major change in the insulin-secreting
      dynamics after glucose loading was observed. After weight loss, nateglinide
      administration produced a significant increase in DeltaI30/DeltaG30, with insulin
      secretion peaking more quickly. CONCLUSION: Insulin response to nateglinide after
      glucose loading varied greatly in conjunction with weight loss. This may be
      accounted for not only by the enhancement of early insulin response to
      nateglinide associated with the improvement of early insulin response with weight
      loss but also by the reduced visceral fat, which in turn led to reduced levels of
      free fatty acids in portal blood and hepatic triglycerides, as well as increased
      hepatic insulin clearance.

PMID- 15715890
TI  - Improvement of glucose tolerance in Zucker diabetic fatty rats by long-term
      treatment with the dipeptidyl peptidase inhibitor P32/98: comparison with and
      combination with rosiglitazone.
AB  - AIM: The aim of this study was to investigate the effect of long-term treatment
      with the dipeptidyl peptidase inhibitor P32/98 and its combination with
      rosiglitazone on blood glucose control and islet of Langerhans histology in male
      Zucker diabetic fatty (ZDF) rats, when treatment begins before or after the
      development of overt diabetes. METHODS: ZDF rats were treated with P32/98 from
      the age of 9, 12 or 15 weeks. Rosiglitazone maleate was given to a separate group
      from the age of 13 weeks. P32/98 was given to all of these rosiglitazone-treated
      rats from 16 weeks of age. Rosiglitazone maleate was also given from 16 weeks of
      age to half the rats that were given P32/98 from 9 weeks of age. The compounds
      were given by oral gavage until the rats were 14 weeks old and then in the diet.
      The experiment was terminated at the age of 20-21 weeks. Blood glucose, plasma
      insulin and oral glucose tolerance were measured at intervals; islet histology
      was assessed terminally. RESULTS: P32/98 improved glucose tolerance after both
      single and multiple doses when treatment started at 9 weeks of age, also after
      the third week of treatment when treatment began at 12 or 15 weeks of age. P32/98
      reduced daytime blood glucose when treatment began at 12 weeks. Treatment with
      rosiglitazone increased food intake and body weight, and after 2 weeks, reduced
      daytime blood glucose, water intake and the area under the glucose tolerance
      curve. A single dose of P32/98 markedly improved glucose tolerance in
      rosiglitazone-treated rats. When treatment had begun at 9 weeks of age, P32/98
      stimulated insulin secretion in some glucose tolerance tests. Neither P32/98 nor
      rosiglitazone affected pancreatic insulin content, nor did they have clear
      effects on islet histology. CONCLUSION: P32/98 elicited a sustained improvement
      in glucose tolerance in both prediabetic and diabetic ZDF rats. The effects of
      P32/98 on glucose and insulin were similar to those of rosiglitazone, and in
      contrast to rosiglitazone, P32/98 did not increase food intake or body weight.
      However, neither compound was especially effective at improving diabetes in ZDF
      rats when treatment began at 9, 12 or 15 (P32/98) or 13 (rosiglitazone) weeks of
      age.

PMID- 15715892
TI  - Effects of metformin on the body composition in subjects with risk factors for
      type 2 diabetes.
AB  - OBJECTIVES: To measure the effect of metformin on the body composition, insulin
      resistance and sensitivity in subjects with risk factors for type 2 diabetes
      mellitus (type 2 DM). DESIGN: Placebo-controlled clinical trial. MATERIAL AND
      METHODS: Twenty-three subjects with risk factors for type 2 DM were randomly
      assigned to receive 850 mg of metformin or a placebo twice a day for 2 months.
      Before and after the treatment, the body mass index and waist/hip ratio were
      calculated, the body composition was measured through bioelectric impedance and
      the fasting levels of blood glucose, insulin, triglycerides and cholesterol were
      measured. The level of insulin resistance was calculated by the homeostatic model
      and the level of sensitivity by the quantitative insulin sensitivity check index
      method. The Wilcoxon rank test was used. RESULTS: Twenty-one subjects completed
      the study, 12 of the metformin group and nine of the placebo group. In the
      metformin group, there was a decrease in fat weight from 25.9 +/- 9.4 to 20.8 +/-
      9.2 kg, p < 0.01, an increase in lean weight from 57.05 +/- 13.6 to 61.9 +/- 16.5
      kg, p < 0.01, an increase in basal metabolism from 1735 +/- 413 to 1878 +/- 505
      calories/day, p < 0.05 and an increase in body water, p < 0.05. There was no
      significant decrease in insulin resistance. In the placebo group, the blood
      glucose increased from 84.7 +/- 13 to 96.7 +/- 16 mg/dl, p < 0.05. There were no
      significant modifications in lipids. CONCLUSIONS: The administration of metformin
      for 2 months improves the parameters of body composition and insulin dynamics in
      subjects with risk factors for type 2 DM.

PMID- 15715893
TI  - Effects of a novel formulation of essential oils on glucose-insulin metabolism in
      diabetic and hypertensive rats: a pilot study.
AB  - BACKGROUND: Insulin resistance and its most severe form type 2 diabetes mellitus
      are rapidly increasing throughout the world. It is generally recognized that
      natural products with a long history of safety can increase insulin sensitivity.
      AIMS: The present investigation examined the ability of various combinations of
      essential oils such as fenugreek, cinnamon, cumin, oregano, etc. to enhance
      insulin sensitivity. As a first approximation, we examined the effects of these
      natural products on Zucker fatty rats (ZFRs), a model of obesity and insulin
      resistance, and spontaneously hypertensive rats (SHRs), a model of genetic
      hypertension. MATERIAL AND METHODS: Water or essential oils were given orally via
      droplets, and insulin sensitivity was estimated by systolic blood pressure (SBP)
      changes and circulating glucose and/or insulin concentrations. RESULTS: We have
      found that the ability to alter SBP in rat models is the most sensitive early
      index of insulin sensitivity. The combined essential oils lowered circulating
      glucose levels and SBP in both ZFRs and SHRs, suggesting that these natural
      products are enhancing insulin sensitivity. The second series of studies examined
      two additional combinations of essential oils along with the original formula.
      The major differences were in the types and proportions of individual oils
      contributing to a given formula. CONCLUSIONS: Although all the three formulae
      decreased SBP in ZFRs, one of the formulae was more effective than the others in
      lowering circulating glucose in the glucose tolerance testing. Accordingly, some
      essential oils may be added to the long list of natural products that can affect
      insulin sensitivity.

PMID- 15715897
TI  - Collaboration, continuity, compliance: two fellows "share" their experiences.

PMID- 15715894
TI  - Cataracts in experimentally diabetic mouse: morphological and apoptotic changes.
AB  - AIM: The objective of these investigations was to extend our earlier study on the
      induction of cataracts in diabetic mice, a low aldose reductase (AR) animal model
      at morphological level. Previous studies were done primarily at biochemical
      level. METHODS: Diabetes was induced by intraperitoneal administration of
      streptozotocin. The lenses isolated after the establishment of diabetes were then
      subjected to histologic and electron microscopic studies. RESULTS: Morphological
      alterations were characterized by shrinkage, elongation and lobulization of the
      nuclei of the epithelial cells. This was associated with chromatin condensation
      and its margination. Similar structural aberrations were also observed in a
      significant number of the subepithelial fibre cells representing defect in fibre
      maturation. More interestingly, unlike that in other common animal models of
      diabetic cataract, such abnormally nucleated cells were also found to be
      prevalent in the posterior subcapsular region, a finding common in human
      diabetics also. CONCLUSION: The present studies further affirm the suitability of
      the mouse model for a study of cataractogenesis induced by diabetes. Because of
      the findings reported herein, as well as the known biochemical similarity between
      the lenses of the mice and humans in respect of AR deficiency, contrary to the
      rat model where it is very high, use of this species is considered more useful
      towards understanding the basic aetiology as well as for evaluating the efficacy
      of various referred nutritional and metabolic antioxidants against such
      cataracts.

PMID- 15715898
TI  - A community-oriented primary care nursing model in an international setting that
      emphasizes partnerships.
AB  - PURPOSE: To present an interdisciplinary, community-oriented primary care nursing
      model that effectively draws upon the strengths of advanced practice nurses
      (APNs), both nurse practitioners and community health nurses. DATA SOURCES:
      Articles in professional nursing journals, international data sources, and the
      clinical experiences of the authors, both domestic and international.
      CONCLUSIONS: The model, developed domestically, was utilized successfully by APNs
      internationally in a medical mission endeavor in rural Haiti. Many partners,
      domestic and Haitian, worked as an interdisciplinary team to deliver quality
      health care to an impoverished population. Graduate nursing students participated
      in the program, which offered opportunities and challenges for both novice and
      expert nurses. IMPLICATIONS FOR PRACTICE: Nurse practitioners, community health
      nurses, and nursing faculty members can use this model to enhance their
      professional practice. They can learn that clients can be optimally cared for
      whether the community served is domestic or international. Nursing faculty can
      teach graduate nursing students about the value of partnerships and
      collaboration.

PMID- 15715899
TI  - Recognizing and managing patients with irritable bowel syndrome.
AB  - PURPOSE: To address the diagnosis and clinical management of irritable bowel
      syndrome (IBS) and provide a discussion of the available serotonergic agents.
      DATA SOURCES: Recent studies examining the pathophysiology of IBS. CONCLUSIONS:
      Diagnostic testing may be required in the subset of patients with IBS who present
      with alarm symptoms, or "red flags," suggestive of underlying organic disease. An
      important role has been suggested for the neurotransmitter serotonin in both gut
      motility and visceral pain sensitivity. IMPLICATIONS FOR PRACTICE: A diagnosis of
      IBS is largely based on symptoms; therefore, effective clinician-patient
      communication and careful attention to details of patient presentation, history,
      and physical examination are essential.

PMID- 15715900
TI  - Exercise as a treatment for depression in elders.
AB  - PURPOSE: To describe the use of exercise when treating depression in elders and
      to discuss the data supporting the relationship between increased physical
      activity and decreased depression. DATA SOURCES: Extensive review of recent
      scientific literature, both medical and gerontological in content. CONCLUSIONS:
      Increasing physical activity markedly reduces depressive symptoms and is a safe
      adjunct or alternative to medication therapy. IMPLICATIONS FOR PRACTICE: Exercise
      has numerous physical and psychological benefits to patients. Physical activity
      should be recommended to all patients of all ages.

PMID- 15715901
TI  - The use of personal digital assistants by nurse practitioner students and
      faculty.
AB  - PURPOSE: To describe the prevalence and patterns of use of personal digital
      assistants (PDAs) by nurse practitioner (NP) students and faculty, examine
      relationships between patterns of use of PDAs and demographic characteristics of
      NP students and faculty, and describe patterns of use of PDAs that support
      evidence-based practice (clinical scholarship). DATA SOURCES: Responses to a 20
      item questionnaire administered via electronic or postal mail from 227 NP
      students and faculty. CONCLUSIONS: A majority (67%) of the participants used
      PDAs. Use was higher among men (82%) than women (64%) (p < .05). On average,
      respondents who used a PDA (N = 153) had been using it just over a year (M = 13
      months). Respondents reported using a PDA most days of the week (M = 5 days). The
      top three medical software programs identified by respondents as the most useful
      in clinical practice were ePocrates Rx (82%), Griffith's 5-Minute Clinical
      Consult (26%), and MedCalc (22%). Most participants (96%) related that PDA use
      supported clinical decision making. IMPLICATIONS FOR PRACTICE: Personal digital
      assistants may facilitate the application of evidence-based knowledge to
      practice. However, until there is evidence that PDA software is valid and
      reliable, clinicians should continue to use a multitude of references to assure
      the quality and safety of care provided.

PMID- 15715902
TI  - Moral problems and distress among nurse practitioners in primary care.
AB  - PURPOSE: To identify the ethical issues nurse practitioners (NPs) encounter in
      primary care, examine the types of moral problems that arise related to those
      issues, and determine the level of distress NPs experience. DATA SOURCE: Self
      reported responses to an investigator-designed, anonymous, mailed survey on a
      convenience sample of 71 NPs practicing in primary care in one midwestern
      metropolitan area. CONCLUSIONS: This preliminary descriptive study identified a
      number and variety of ethical issues NPs encounter in primary care. The issue
      encountered with the greatest frequency was patient refusal of appropriate
      treatment. Distress was reported most often over problems of moral dilemma,
      followed by moral distress, and least often, moral uncertainty and moral outrage.
      Another type of moral problem, possibly related to conflict between patient
      autonomy and NP beneficence, occurred almost as often as moral dilemma. Not as
      many NPs reported encountering ethical issues or being distressed as the
      literature suggests. The reason for this is unclear but may be related to NPs'
      sense of moral responsibility or their ability to discern subtle ethical issues
      in the complex primary care environment. Regardless of moral problem, NPs felt
      frustrated and powerless. As a result, some changed jobs and contemplated leaving
      advanced practice. IMPLICATIONS FOR PRACTICE: More research is needed to clearly
      understand ethical issues and moral problems for NPs in primary care, how NPs
      identify and manage problems, and the effects on NPs and patients.

PMID- 15715903
TI  - A case-control study to evaluate urinary tract complications in radical
      hysterectomy.
AB  - BACKGROUND: This study has evaluated urinary tract injuries and dysfunction after
      Radical Hysterectomy (RH) performed in patients with cervical cancer and has
      compared the cystometric parameters and urinary complications occurring in these
      patients with those occurring in patients who had undergone Simple Hysterectomy
      (SH). PATIENTS AND METHODS: A prospective case-control study was conducted to
      evaluate urinary tract injuries (intra-operative and post-operative) and
      dysfunction in 50 patients undergoing RH for cervical cancer and to compare them
      with the same parameters in 50 patients who underwent SH for benign disease.
      RESULTS: Mean age in the RH group was 46.3 years and in the SH group was 50.1 (p
      = 0.63). There were no bladder and urethral injuries in either group of patients.
      There was one intra-operative ureteral injury in the RH patients but none in
      those who underwent SH. (p < 0.05). In the two weeks after surgery, 15% of RH
      patients and 11% of SH patients had experienced a urinary tract infection urinary
      tract infection (p = 0.61). Two week after surgery 62% of RH patients had no
      urinary symptoms, compared to 84% in the SH group who did (p < 0.02). Urinary
      residual volume, first urinary sensation and maximal bladder capacity were higher
      in the RH group, but this was not statistically significant. The only case of a
      urinary fistula appeared in a patient who received 5000 cGy radiation therapy pre
      operatively, but this spontaneously healed after 3 weeks of catheterization.
      CONCLUSIONS: Intra-operative and post-operative urinary tract complications are
      comparable in patients undergoing RH and SH and an expert gynaecological
      oncologist might be able to further decrease complications. However, radiation
      therapy before surgery may increase the risk of complications.

PMID- 15715904
TI  - Increasing stability of water-soluble PQQ glucose dehydrogenase by increasing
      hydrophobic interaction at dimeric interface.
AB  - BACKGROUND: Water-soluble quinoprotein glucose dehydrogenase (PQQGDH-B) from
      Acinetobacter calcoaceticus has a great potential for application as a glucose
      sensor constituent. Because this enzyme shows no activity in its monomeric form,
      correct quaternary structure is essential for the formation of active enzyme. We
      have previously reported on the increasing of the stability of PQQGDH-B by
      preventing the subunit dissociation. Previous studies were based on decreasing
      the entropy of quaternary structure dissociation but not on increasing the
      interaction between the two subunits. We therefore attempted to introduce a
      hydrophobic interaction in the dimeric interface to increase the stability of
      PQQGDH-B. RESULTS: Amino acid residues Asn340 and Tyr418 face each other at the
      dimer interface of PQQGDH-B, however no interaction exists between their side
      chains. We simultaneously substituted Asn340 to Phe and Tyr418 to Phe or Ile, to
      create the two mutants Asn340Phe/Tyr418Phe and Asn340Phe/Tyr418Ile. Furthermore,
      residues Leu280, Val282 and Val342 form a hydrophobic region that faces, on the
      other subunit, residues Thr416 and Thr417, again without any specific
      interaction. We simultaneously substituted Thr416 and Thr417 to Val, to create
      the mutant Thr416Val/Thr417Val. The temperatures resulting in lose of half of the
      initial activity of the constructed mutants were increased by 3-4 degrees C
      higher over wild type. All mutants showed 2-fold higher thermal stability at 55
      degrees C than the wild-type enzyme, without decreasing their catalytic
      activities. From the 3D models of all the mutant enzymes, the predicted binding
      energies were found to be significantly greater that in the wild-type enzyme,
      consistent with the increases in thermal stabilities. CONCLUSIONS: We have
      achieved via site-directed mutagenesis the improvement of the thermal stability
      of PQQGDH-B by increasing the dimer interface interaction. Through rational
      design based on the quaternary structure of the enzyme, we selected residues
      located at the dimer interface that do not contribute to the intersubunit
      interaction. By substituting these residues to hydrophobic ones, the thermal
      stability of PQQGDH-B was increased without decreasing its catalytic activity.

PMID- 15715905
TI  - Protein domains and architectural innovation in plant-associated Proteobacteria.
AB  - BACKGROUND: Evolution of new complex biological behaviour tends to arise by novel
      combinations of existing building blocks. The functional and evolutionary
      building blocks of the proteome are protein domains, the function of a protein
      being dependent on its constituent domains. We clustered completely-sequenced
      proteomes of prokaryotes on the basis of their protein domain content, as defined
      by Pfam (release 16.0). This revealed that, although there was a correlation
      between phylogeny and domain content, other factors also have an influence. This
      observation motivated an investigation of the relationship between an organism's
      lifestyle and the complement of domains and domain architectures found within its
      proteome. RESULTS: We took a census of all protein domains and domain
      combinations (architectures) encoded in the completely-sequenced proteobacterial
      genomes. Nine protein domain families were identified that are found in
      phylogenetically disparate plant-associated bacteria but are absent from non
      plant-associated bacteria. Most of these are known to play a role in the plant
      associated lifestyle, but they also included domain of unknown function DUF1427,
      which is found in plant symbionts and pathogens of the alpha-, beta- and gamma
      Proteobacteria, but not known in any other organism. Further, several domains
      were identified as being restricted to phytobacteria and Eukaryotes. One example
      is the RolB/RolC glucosidase family, which is found only in Agrobacterium species
      and in plants. We identified the 0.5% of Pfam protein domain families that were
      most significantly over-represented in the plant-associated Proteobacteria with
      respect to the background frequencies in the whole set of available
      proteobacterial proteomes. These included guanylate cyclase, domains implicated
      in aromatic catabolism, cellulase and several domains of unknown function. We
      identified 459 unique domain architectures found in phylogenetically diverse
      plant pathogens and symbionts that were absent from non-pathogenic and non
      symbiotic relatives. The vast majority of these were restricted to a single
      species or several closely related species and so their distributions could be
      better explained by phylogeny than by lifestyle. However, several architectures
      were found in two or more very distantly related phytobacteria but absent from
      non-plant-associated bacteria. Many of the proteins with these unique
      architectures are predicted to be secreted. In Pseudomonas syringae pathovar
      tomato, those genes encoding genes with novel domain architectures tended to have
      atypical GC contents and were adjacent to insertion sequence elements and phage
      like sequences, suggesting acquisition by horizontal transfer. CONCLUSIONS: By
      identifying domains and architectures unique to plant pathogens and symbionts, we
      highlighted candidate proteins for involvement in plant-associated bacterial
      lifestyles. Given that characterisation of novel gene products in vivo and in
      vitro is time-consuming and expensive, this computational approach may be useful
      for reducing experimental search space. Furthermore we discuss the biological
      significance of novel proteins highlighted by this study in the context of plant
      associated lifestyles.

PMID- 15715906
TI  - Contribution of gap junctional communication between tumor cells and astroglia to
      the invasion of the brain parenchyma by human glioblastomas.
AB  - BACKGROUND: Gliomas are "intraparenchymally metastatic" tumors, invading the
      brain in a non-destructive way that suggests cooperation between glioma cells and
      their environment. Recent studies using an engineered rodent C6 tumor cell line
      have pointed to mechanisms of invasion that involved gap junctional communication
      (GJC), with connexin 43 as a substrate. We explored whether this concept may have
      clinical relevance by analyzing the participation of GJC in human glioblastoma
      invasion. RESULTS: Three complementary in vitro assays were used: (i) seeding on
      collagen IV, to analyze homocellular interactions between tumor cells (ii) co
      cultures with astrocytes, to study glioblastoma/astrocytes relationships and
      (iii) implantation into organotypic brain slice cultures, that mimic the three
      dimensional parenchymal environment. Carbenoxolone, a potent blocker of GJC,
      inhibited cell migration in the two latter models. It paradoxically increased it
      in the first one. These results showed that homocellular interaction between
      tumor cells supports intercellular adhesion, whereas heterocellular
      glioblastoma/astrocytes interactions through functional GJC conversely support
      tumor cell migration. As demonstrated for the rodent cell line, connexin 43 may
      be responsible for this heterocellular functional coupling. Its levels of
      expression, high in astrocytes, correlated positively with invasiveness in
      biopsied tumors. CONCLUSIONS: our results underscore the potential clinical
      relevance of the concept put forward by other authors based on experiments with a
      rodent cell line, that glioblastoma cells use astrocytes as a substrate for their
      migration by subverting communication through connexin 43-dependent gap
      junctions.

PMID- 15715907
TI  - Statistical model of natural stimuli predicts edge-like pooling of spatial
      frequency channels in V2.
AB  - BACKGROUND: It has been shown that the classical receptive fields of simple and
      complex cells in the primary visual cortex emerge from the statistical properties
      of natural images by forcing the cell responses to be maximally sparse or
      independent. We investigate how to learn features beyond the primary visual
      cortex from the statistical properties of modelled complex-cell outputs. In
      previous work, we showed that a new model, non-negative sparse coding, led to the
      emergence of features which code for contours of a given spatial frequency band.
      RESULTS: We applied ordinary independent component analysis to modelled outputs
      of complex cells that span different frequency bands. The analysis led to the
      emergence of features which pool spatially coherent across-frequency activity in
      the modelled primary visual cortex. Thus, the statistically optimal way of
      processing complex-cell outputs abandons separate frequency channels, while
      preserving and even enhancing orientation tuning and spatial localization. As a
      technical aside, we found that the non-negativity constraint is not necessary:
      ordinary independent component analysis produces essentially the same results as
      our previous work. CONCLUSION: We propose that the pooling that emerges allows
      the features to code for realistic low-level image features related to step
      edges. Further, the results prove the viability of statistical modelling of
      natural images as a framework that produces quantitative predictions of visual
      processing.

PMID- 15715908
TI  - An interactional network of genes involved in chitin synthesis in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: In S. cerevisiae the beta-1,4-linked N-acetylglucosamine polymer,
      chitin, is synthesized by a family of 3 specialized but interacting chitin
      synthases encoded by CHS1, CHS2 and CHS3. Chs2p makes chitin in the primary
      septum, while Chs3p makes chitin in the lateral cell wall and in the bud neck,
      and can partially compensate for the lack of Chs2p. Chs3p requires a pathway of
      Bni4p, Chs4p, Chs5p, Chs6p and Chs7p for its localization and activity. Chs1p is
      thought to have a septum repair function after cell separation. To further
      explore interactions in the chitin synthase family and to find processes
      buffering chitin synthesis, we compiled a genetic interaction network of genes
      showing synthetic interactions with CHS1, CHS3 and genes involved in Chs3p
      localization and function and made a phenotypic analysis of their mutants.
      RESULTS: Using deletion mutants in CHS1, CHS3, CHS4, CHS5, CHS6, CHS7 and BNI4 in
      a synthetic genetic array analysis we assembled a network of 316 interactions
      among 163 genes. The interaction network with CHS3, CHS4, CHS5, CHS6, CHS7 or
      BNI4 forms a dense neighborhood, with many genes functioning in cell wall
      assembly or polarized secretion. Chitin levels were altered in 54 of the mutants
      in individually deleted genes, indicating a functional relationship between them
      and chitin synthesis. 32 of these mutants triggered the chitin stress response,
      with elevated chitin levels and a dependence on CHS3. A large fraction of the
      CHS1-interaction set was distinct from that of the CHS3 network, indicating broad
      roles for Chs1p in buffering both Chs2p function and more global cell wall
      robustness. CONCLUSION: Based on their interaction patterns and chitin levels we
      group interacting mutants into functional categories. Genes interacting with CHS3
      are involved in the amelioration of cell wall defects and in septum or bud neck
      chitin synthesis, and we newly assign a number of genes to these functions. Our
      genetic analysis of genes not interacting with CHS3 indicate expanded roles for
      Chs4p, Chs5p and Chs6p in secretory protein trafficking and of Bni4p in bud neck
      organization.

PMID- 15715910
TI  - The Anal Pap Smear: Cytomorphology of squamous intraepithelial lesions.
AB  - BACKGROUND: Anal smears are increasingly being used as a screening test for anal
      squamous intraepithelial lesions (ASILs). This study was undertaken to assess the
      usefulness and limitations of anal smears in screening for ASILs. METHODS: The
      cytomorphological features of 200 consecutive anal smears collected in liquid
      medium from 198 patients were studied and findings were correlated with results
      of surgical biopsies and/or repeat smears that became available for 71 patients
      within six months. RESULTS: Adequate cellularity was defined as an average of 6
      or more nucleated squamous cells/hpf. A glandular/transitional component was not
      required for adequacy. Dysplastic cells, atypical parakeratotic cells and
      bi/multinucleated cells were frequent findings in ASIL while koilocytes were
      infrequent. Smears from LSIL cases most frequently showed mildly dysplastic and
      bi/multinucleate squamous cells followed by parakeratotic cells (PK), atypical
      parakeratotic cells (APK), and koilocytes. HSIL smears contained squamous cells
      with features of moderate/severe dysplasia and many APKs. Features of LSIL were
      also found in most HSIL smears. CONCLUSIONS: In this study liquid based anal
      smears had a high sensitivity (98%) for detection of ASIL but a low specificity
      (50%) for predicting the severity of the abnormality in subsequent biopsy.
      Patients with cytologic diagnoses of ASC-US and LSIL had a significant risk (46
      56%) of HSIL at biopsy. We suggest that all patients with a diagnosis of ASC-US
      and above be recommended for high resolution anoscopy with biopsy.

PMID- 15715909
TI  - Cancer/testis antigens and gametogenesis: a review and "brain-storming" session.
AB  - Genes expressed both in normal testis and in malignancies (Cancer/ Testis
      associated genes - CTA) have become the most extensively studied antigen group in
      the field of tumour immunology. Despite this, many fundamentally important
      questions remain unanswered: what is the connection between germ-cell specific
      genes and tumours? Is the expression of these genes yet another proof for the
      importance of genome destabilisation in the process of tumorigenesis?, or maybe
      activation of these genes is not quite random but instead related to some
      programme giving tumours a survival advantage?This review collates most of the
      recent information available about CTAs expression, function, and regulation. The
      data suggests a programme related to ontogenesis, mostly to gametogenesis. In the
      "brain-storming" part, facts in conflict with the hypothesis of random CTA gene
      activation are discussed. We propose a programme borrowed from organisms
      phylogenetically much older than humans, which existed before the differentiation
      of sexes. It is a programme that has served as a life cycle with prominent ploidy
      changes, and from which, as we know, the germ-cell ploidy cycle - meiosis - has
      evolved. Further work may show whether this hypothesis can lead to a novel anti
      tumour strategy.

PMID- 15715911
TI  - Anal screening cytology.
AB  - This issue of CytoJournal contains an article on screening for anal
      intraepithelial neoplasia in high-risk male patients. This accompanying Editorial
      focuses on current understanding of this relatively new disease entity, with
      insights as to the potential role of screening cytopathology in the epidemiology,
      pathophysiology and clinical management of this HIV and HPV related anal lesion,
      which predominates in male patients living long-term with AIDS. Mention is made
      of techniques of obtaining samples, methods of preparation, and morphologic
      classification. Issues of anoscopic confirmation, as well as topical and surgical
      management are emphasized. The similarity of initial experiences in anal
      screening to problems encountered early in cervical cancer screening programs
      several decades ago, are highlighted.

PMID- 15715912
TI  - Direct analysis of thymic function in children with Down's syndrome.
AB  - BACKGROUND: Down's syndrome (DS) is characterized by several immunological
      defects, especially regarding T cell compartment. DS is considered the best
      example of accelerated ageing in humans. Direct observations of the thymus have
      shown that in DS this organ undergoes severe histological and morphological
      changes. However, no data on its capacity to generate T cells are present in the
      literature. Here, using a new technology based upon real time PCR, we have
      investigated the capacity of the thymus to produce and release newly generated T
      lymphocytes (the so called "recent thymic emigrants", RTE) in children with DS.
      METHODS: We studied 8 children affected by DS, aged 2-7 years, compared with 8
      age- and sex-matched healthy controls. Flow cytometry was used to determine
      different lymphocytes subsets. Real time PCR with the Taqman system was used to
      quantify the amount of RTE, i.e. peripheral blood lymphocytes that express the T
      cell receptor rearrangement excision circles (TREC). RESULTS: In comparison with
      control children, those with DS had a significant lower number of TREC+
      peripheral blood cells. Moreover, in DS children but not in controls, a strong
      negative correlation between age and the levels of TREC+ cells was found.
      CONCLUSIONS: The direct measure of thymic output indicates that the impairment of
      the organ results in a reduced production of newly generated T cells. This
      observation could suggest that cytokines able to modulate thymic function, such
      as interleukins, could be useful to improve the functionality of the organ and to
      treat the immunodeficiency present in DS subjects.

PMID- 15715913
TI  - Molecular strategies to inhibit HIV-1 replication.
AB  - The human immunodeficiency virus type 1 (HIV-1) is the primary cause of the
      acquired immunodeficiency syndrome (AIDS), which is a slow, progressive and
      degenerative disease of the human immune system. The pathogenesis of HIV-1 is
      complex and characterized by the interplay of both viral and host factors. An
      intense global research effort into understanding the individual steps of the
      viral replication cycle and the dynamics during an infection has inspired
      researchers in the development of a wide spectrum of antiviral strategies.
      Practically every stage in the viral life cycle and every viral gene product is a
      potential target. In addition, several strategies are targeting host proteins
      that play an essential role in the viral life cycle. This review summarizes the
      main genetic approaches taken in such antiviral strategies.

PMID- 15715914
TI  - Evaluation of an education and activation programme to prevent chronic shoulder
      complaints: design of an RCT [ISRCTN71777817].
AB  - BACKGROUND: About half of all newly presented episodes of shoulder complaints
      (SC) in general practice are reported to last for at least six months. Early
      interventions aimed at the psychological and social determinants of SC are not
      common in general practice, although such interventions might prevent the
      development of chronic SC. The Education and Activation Programme (EAP) consists
      of an educational part and a time-contingent activation part. The aim of the EAP
      is to provide patients with the proper cognitions by means of education, and to
      stimulate adequate behaviour through advice on activities of daily living.
      DESIGN: The article describes the design of a randomised clinical trial (RCT) to
      evaluate the effectiveness and cost-effectiveness of an EAP in addition to usual
      care, compared to usual care only, in the prevention of chronic SC after six
      months. It also describes the analysis of the cost and effect balance. Patients
      suffering from SC for less than three months are recruited in general practice
      and through open recruitment. A trained general practitioner or a trained
      therapist administers the EAP.Primary outcome measures are patient-perceived
      recovery, measured by self-assessment on a seven-point scale, and functional
      limitations in activities of daily living. Questionnaires are used to study
      baseline measures, prognostic measures, process measures and outcome measures.
      DISCUSSION: The inclusion of patients in the study lasted until December 31st
      2003. Data collection is to end in June 2004.

PMID- 15715915
TI  - Opisthobranchia (Mollusca, Gastropoda) - more than just slimy slugs. Shell
      reduction and its implications on defence and foraging.
AB  - BACKGROUND: In general shell-less slugs are considered to be slimy animals with a
      rather dull appearance and a pest to garden plants. But marine slugs usually are
      beautifully coloured animals belonging to the less-known Opisthobranchia. They
      are characterized by a large array of interesting biological phenomena, usually
      related to foraging and/or defence. In this paper our knowledge of shell
      reduction, correlated with the evolution of different defensive and foraging
      strategies is reviewed, and new results on histology of different glandular
      systems are included. RESULTS: Based on a phylogeny obtained by morphological and
      histological data, the parallel reduction of the shell within the different
      groups is outlined. Major food sources are given and glandular structures are
      described as possible defensive structures in the external epithelia, and as
      internal glands. CONCLUSION: According to phylogenetic analyses, the reduction of
      the shell correlates with the evolution of defensive strategies. Many different
      kinds of defence structures, like cleptocnides, mantle dermal formations (MDFs),
      and acid glands, are only present in shell-less slugs. In several cases, it is
      not clear whether the defensive devices were a prerequisite for the reduction of
      the shell, or reduction occurred before. Reduction of the shell and acquisition
      of different defensive structures had an implication on exploration of new food
      sources and therefore likely enhanced adaptive radiation of several groups.

PMID- 15715916
TI  - Evaluating the role of quality assessment of primary studies in systematic
      reviews of cancer practice guidelines.
AB  - BACKGROUND: The purpose of this study was to evaluate the role of study quality
      assessment of primary studies in cancer practice guidelines. METHODS: Reliable
      and valid study quality assessment scales were sought and applied to published
      reports of trials included in systematic reviews of cancer guidelines.
      Sensitivity analyses were performed to evaluate the relationship between quality
      scores and pooled odds ratios (OR) for mortality and need for blood transfusion.
      RESULTS: Results found that that whether trials were classified as high or low
      quality depended on the scale used to assess them. Although the results of the
      sensitivity analyses found some variation in the ORs observed, the confidence
      intervals (CIs) of the pooled effects from each of the analyses of high quality
      trials overlapped with the CI of the pooled odds of all trials. Quality score was
      not predictive of pooled ORs studied here. CONCLUSIONS: Had sensitivity analyses
      based on study quality been conducted prospectively, it is highly unlikely that
      different conclusions would have been found or that different clinical
      recommendations would have emerged in the guidelines.

PMID- 15715917
TI  - Integrating quantitative and qualitative methodologies for the assessment of
      health care systems: emergency medicine in post-conflict Serbia.
AB  - BACKGROUND: Due to the complexity of health system reform in the post-conflict,
      post-disaster, and development settings, attempts to restructure health services
      are fraught with pitfalls that are often unanticipated because of inadequate
      preliminary assessments. Our proposed Integrated Multimodal Assessment -
      combining quantitative and qualitative methodologies - may provide a more robust
      mechanism for identifying programmatic priorities and critical barriers for
      appropriate and sustainable health system interventions. The purpose of this
      study is to describe this novel multimodal assessment using emergency medicine in
      post-conflict Serbia as a model. METHODS: Integrated quantitative and qualitative
      methodologies--system characterization and observation, focus group discussions,
      free-response questionnaires, and by-person factor analysis--were used to
      identify needs, problems, and potential barriers to the development of emergency
      medicine in Serbia. Participants included emergency and pre-hospital personnel
      from all emergency medical institutions in Belgrade. RESULTS: Demographic data
      indicate a loosely ordered network of part-time emergency departments supported
      by 24-hour pre-hospital services and an academic emergency center. Focus groups
      and questionnaires reveal significant impediments to delivery of care and suggest
      development priorities. By-person factor analysis subsequently divides
      respondents into distinctive attitudinal types, compares participant opinions,
      and identifies programmatic priorities. CONCLUSIONS: By combining quantitative
      and qualitative methodologies, our Integrated Multimodal Assessment identified
      critical needs and barriers to emergency medicine development in Serbia and may
      serve as a model for future health system assessments in post-conflict, post
      disaster, and development settings.

PMID- 15715919
TI  - A new season of Chinese cardiovascular pharmacology research.

PMID- 15715918
TI  - Antiglucocorticoid RU38486 reduces net protein catabolism in experimental acute
      renal failure.
AB  - BACKGROUND: In acute renal failure, a pronounced net protein catabolism occurs
      that has long been associated with corticoid action. By competitively blocking
      the glucocorticoid receptor with the potent antiglucocorticoid RU 38486, the
      present study addressed the question to what extent does corticoid action
      specific to uremia cause the observed muscle degradation, and does inhibition of
      glucocorticoid action reduce the protein wasting? METHODS: RU 38486 was
      administered in a dose of 50 mg/kg/24 h for 48 h after operation to fasted
      bilaterally nephrectomized (BNX) male adult Wistar rats and sham operated (SHAM)
      controls. Protein turnover was evaluated by high performance liquid
      chromatography (HPLC) of amino acid efflux in sera from isolated perfused
      hindquarters of animals treated with RU 38486 versus untreated controls. RESULTS:
      Administration of RU 38486 reduces the total amino acid efflux (TAAE) by 18.6% in
      SHAM and 15.6% in BNX and efflux of the indicator of net protein turnover,
      phenylalanine (Phe) by 33.3% in SHAM and 13% in BNX animals as compared to the
      equally operated, but untreated animals. However, the significantly higher
      protein degradation observed in BNX (0.6 +/- 0.2 nmol/min/g muscle) versus SHAM
      (0.2 +/- 0.1 nmol/min/g muscle) rats, as demonstrated by the marker of
      myofribrillar proteolytic rate, 3-Methylhistidine (3 MH) remains unaffected by
      administration of RU 38486 (0.5 +/- 0.1 v. 0.2 +/- 0.1 nmol/min/g muscle in BNX
      v. SHAM). CONCLUSION: RU 38486 does not act on changes of muscular protein
      turnover specific to uremia but reduces the effect of stress-stimulated elevated
      corticosterone secretion arising from surgery and fasting. A potentially
      beneficial effect against stress- induced catabolism in severe illness can be
      postulated that merits further study.

PMID- 15715920
TI  - Nitric oxide: a newly discovered function on wound healing.
AB  - Wound healing impairment represents a particularly challenging clinical problem
      to which no efficacious treatment regimens currently exist. The factors ensuring
      appropriate intercellular communication during wound repair are not completely
      understood. Although protein-type mediators are well-established players in this
      process, emerging evidence from both animal and human studies indicates that
      nitric oxide (NO) plays a key role in wound repair. The beneficial effects of NO
      on wound repair may be attributed to its functional influences on angiogenesis,
      inflammation, cell proliferation, matrix deposition, and remodeling. Recent
      findings from in vitro and in vivo studies of NO on wound repair are summarized
      in this review. The unveiled novel mechanisms support the use of NO-containing
      agents and/or NO synthase gene therapy as new therapeutic regimens for impaired
      wound healing.

PMID- 15715921
TI  - Functional role of anion channels in cardiac diseases.
AB  - In comparison to cation (K+, Na+, and Ca2+) channels, much less is currently
      known about the functional role of anion (Cl-) channels in cardiovascular
      physiology and pathophysiology. Over the past 15 years, various types of Cl-
      currents have been recorded in cardiac cells from different species including
      humans. All cardiac Cl- channels described to date may be encoded by five
      different Cl- channel genes: the PKA- and PKC-activated cystic fibrosis
      tansmembrane conductance regulator (CFTR), the volume-regulated ClC-2 and ClC-3,
      and the Ca2+-activated CLCA or Bestrophin. Recent studies using multiple
      approaches to examine the functional role of Cl- channels in the context of
      health and disease have demonstrated that Cl- channels might contribute to: 1)
      arrhythmogenesis in myocardial injury; 2) cardiac ischemic preconditioning; and
      3) the adaptive remodeling of the heart during myocardial hypertrophy and heart
      failure. Therefore, anion channels represent very attractive novel targets for
      therapeutic approaches to the treatment of heart diseases. Recent evidence
      suggests that Cl- channels, like cation channels, might function as a
      multiprotein complex or functional module. In the post-genome era, the emergence
      of functional proteomics has necessitated a new paradigm shift to the structural
      and functional assessment of integrated Cl- channel multiprotein complexes in the
      heart, which could provide new insight into our understanding of the underlying
      mechanisms responsible for heart disease and protection.

PMID- 15715922
TI  - Small guanine nucleotide-binding protein Rho and myocardial function.
AB  - RhoA and Rho-kinase (ROCK) participate in a wide variety of cell signal functions
      such as cell growth, smooth and cardiac muscle contraction, cytoskeleton
      rearrangement, cell migration and proliferation. In vascular smooth muscle cells,
      RhoA and ROCK play an important role in Ca2+ sensitization and regulate vascular
      smooth muscle tone. In the heart, RhoA and ROCK mediate hypertrophic response
      leading to cardiac hypertrophy. Recent cellular and molecular biology studies
      using ROCK inhibitors such as Y-27632 and fasudil have indicated a pivotal role
      of the RhoA-ROCK cascade in many aspects of cardiovascular function such as
      cardiac hypertrophy and ventricular remodeling following myocardial infarction.
      Inhibition of the RhoA-ROCK signaling pathway may be a suitable target for a
      number of cardiovascular diseases including hypertension, atherosclerosis,
      diabetes and hypertrophic heart failure. This review focuses on the current
      understanding of the RhoA-ROCK signal pathway in heart diseases and discusses the
      use of ROCK inhibitors as therapeutic agents for heart diseases ranging from
      hypertensive cardiomyopathy to heart failure.

PMID- 15715923
TI  - The vanilloid receptor and hypertension.
AB  - Mammalian transient receptor potential (TRP) channels consist of six related
      protein sub-families that are involved in a variety of pathophysiological
      function, and disease development. The TRPV1 channel, a member of the TRPV sub
      family, is identified by expression cloning using the "hot" pepper-derived
      vanilloid compound capsaicin as a ligand. Therefore, TRPV1 is also referred as
      the vanilloid receptor (VR1) or the capsaicin receptor. VR1 is mainly expressed
      in a subpopulation of primary afferent neurons that project to cardiovascular and
      renal tissues. These capsaicin-sensitive primary afferent neurons are not only
      involved in the perception of somatic and visceral pain, but also have a "sensory
      effector" function. Regarding the latter, these neurons release stored
      neuropeptides through a calcium-dependent mechanism via the binding of capsaicin
      to VR1. The most studied sensory neuropeptides are calcitonin gene-related
      peptide (CGRP) and substance P (SP), which are potent vasodilators and
      natriuretic/diuretic factors. Recent evidence using the model of neonatal
      degeneration of capsaicin-sensitive sensory nerves revealed novel mechanisms that
      underlie increased salt sensitivity and several experimental models of
      hypertension. These mechanisms include insufficient suppression of plasma renin
      activity and plasma aldosterone levels subsequent to salt loading, enhancement of
      sympathoexcitatory response in the face of a salt challenge, activation of the
      endothelin-1 receptor, and impaired natriuretic response to salt loading in
      capsaicin-pretreated rats. These data indicate that sensory nerves counterbalance
      the prohypertensive effects of several neurohormonal systems to maintain normal
      blood pressure when challenged with salt loading. The therapeutic utilities of
      vanilloid compounds, endogenous agonists, and sensory neuropeptides are also
      discussed.

PMID- 15715924
TI  - Historic perspectives and recent advances in major animal models of hypertension.
AB  - Hypertension and related cardiovascular diseases are the leading causes of death
      in many countries. The etiology of human essential hypertension is largely
      unknown. It is highly likely that hypertension is a complex and multifactorial
      disease resulting from the interaction of multiple genetic and environmental
      factors. Animal models of hypertension have been proved to be useful to study the
      pathogenesis of, and to find a new therapy for, hypertension. The aim of this
      article is to briefly review the most widely used rodent models of experimental
      hypertension, including history and recent advances. These models are classified
      as genetically-induced, environmentally-induced, pharmacologically-induced, and
      renal-induced hypertension according to the way of induction; the typical
      representatives of each of these major types of experimental hypertension are
      spontaneous hypertension, cold-induced hypertension, DOCA-salt-induced
      hypertension, and renal-induced hypertension, respectively. The processes of
      induction of hypertension, possible pathogenesis, characteristics, advantages,
      and limitations of these animal models are reviewed. In addition, the clinical
      implications of the above experimental models of hypertension are addressed.

PMID- 15715925
TI  - Exo+ proofreading polymerases mediate genetic analysis and its application in
      biomedical studies.
AB  - Polymerases with a proofreading function in their internal 3' to 5' exonuclease
      possess high fidelity for DNA replication both in vivo and in vitro. The obstacle
      facing Exo+ polymerases for single nucleotide polymorphism (SNP) detection could
      be bypassed by using primer-3'-termini modification. This hypothesis has been
      well tested using three types of modified allele specific primers with: 3'
      labeling, 3' to 5' exonuclease resistance, and 3' dehydroxylation. Accordingly,
      three new SNP assaying methods have been developed to carry out genome-wide
      genotyping, taking advantage of the enzymatic properties of Exo+ polymerases.
      These new mutation detection assays are widely adaptable to a variety of
      platforms, including multi-well plate and microarray technologies. Application of
      Exo+ polymerases to genetic analysis, including genotyping that is mostly
      relevant to pharma-cogenetics, high-fidelity gene expression profiling, rare
      mutation detection and mutation load assay, will help to accelerate the pace of
      personalized medicine. In this review paper, we will first introduce three new
      assays that we have recently developed, and then describe a number of their
      applications in pharmacogenetics and in other biomedical studies.

PMID- 15715926
TI  - Gene expression profile induced by oral administration of baicalin and gardenin
      after focal brain ischemia in rats.
AB  - AIM: To investigate differential gene expression and the pharmacological
      mechanism of baicalin and gardenin in focal cerebral ischemia in rats with high
      density cDNA microarray. METHODS: Rat left middle cerebral arteries were occluded
      and treated with either baicalin or gardenin. The pharmacological effects were
      investigated using the difference in infarction areas before and after treatment,
      which were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Gene
      expression was demonstrated using a "Biostar40S" gene microarray.
      Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was
      used to verify the result of the selected genes. RESULTS: Both baicalin and
      gardenin reduced the infarction areas in focal cerebral ischemia rats (P<0.05).
      The differential genes were 211, 177, and 70 (upregulated or downregulated) in
      the model group, baicalin, and gardenin treatment groups compared with the sham
      operated group, respectively. Gene expression of RpL19 and Csnk2 underwent an
      approximately 1.9 and 2.1-fold increase, respectively, verified by
      semiquantitative RT-PCR, which was the same trend as the cDNA microarray.
      CONCLUSION: Differential gene expression with respect to the pharmacological
      effects of baicalin and gardenin on focal cerebral ischemia by cDNA microarray
      revealed a number of clues with respect to the therapeutic mechanisms of Chinese
      traditional medicine. In addition, the present study provided theoretical and
      experimental evidence that will aid future studies examining cerebral ischemia.

PMID- 15715927
TI  - Inducible nitric oxide synthase contributes to intermittent hypoxia against
      ischemia/reperfusion injury.
AB  - AIM: To investigate the role of inducible nitric oxide synthase (iNOS)-derived
      nitric oxide (NO) in the cardioprotection of intermittent hypoxia (IH) against
      ischemia/reperfusion (I/R) injury. METHODS: Langendorff-perfused isolated rat
      hearts were used to measure variables of left ventricular function during
      baseline perfusion, ischemia, and reperfusion period. Nitrate plus nitrite (NOx)
      content in myocardium was measured using a biochemical method. iNOS mRNA and
      protein expression in rat left ventricles were detected using reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot, respectively.
      RESULTS: Myocardial function recovered better in IH rat hearts than in normoxic
      control hearts. The iNOS-selective inhibitor aminoguanidine (AG) (100 micromol/L)
      significantly inhibited the protective effects of IH, but had no influence on
      normoxic rat hearts. The baseline content of NOx in IH hearts was higher than
      that in normoxic hearts. After 30 min ischemia, the NOx level in normoxic hearts
      increased compared to the corresponding baseline level, whereas there was no
      significant change in IH hearts. However, the NOx level in IH hearts was still
      higher than that of normoxic hearts during ischemia and reperfusion period. AG
      100 micromol/L significantly diminished the NOx content in IH and normoxic hearts
      during ischemia and reperfusion period. The baseline levels of iNOS mRNA and
      protein in IH hearts were higher than those of normoxic hearts. Compared to the
      corresponding baseline level, iNOS mRNA and protein levels in normoxic rat hearts
      increased and those in IH rat hearts decreased after reperfusion. The addition of
      AG 100 micromol/L significantly decreased iNOS mRNA and protein expression in IH
      rat hearts after I/R. CONCLUSION: IH upregulated the baseline level of iNOS mRNA
      and protein expression leading to an increase in NO production, which may play an
      important role in the cardiac protection of IH against I/R injury.

PMID- 15715928
TI  - Regulation of intracellular Ca2+ and calcineurin by NO/PKG in proliferation of
      vascular smooth muscle cells.
AB  - AIM: To determine whether Ca2+/calcineurin mediated the inhibitory effects of
      nitric oxide /cGMP-dependent protein kinase (NO/PKG) on the proliferation of
      vascular smooth muscle cells (VSMC). METHODS: Proliferation and viability of
      primary VSMC from rat aorta were measured using [3-(4,5-dimethyl thiazol-2-yl)
      2,5-diphenyl tetrazolium bromide] (MTT) assay and acridine orange and ethidium
      bromide staining, respectively. Cytosolic Ca2+ was determined by Fluo-3/AM.
      Calcineurin protein and its activity were assayed using immunoblotting and free
      inorganic phosphate analysis, respectively. RESULTS: (+/-)-S-nitroso-N-acetyl
      penicillamine (SNAP) and Sp-8-(4-chlorophenylthio)-guanosine-3',5'-cyclic
      monophosphorothioate (Sp-8-pCPT-cGMPS) decreased phenylephrine (PE)-induced
      proliferation of VSMC by 27.3% and 36.6%, respectively, but Rp-8-[(4
      chlorophenyl)thio]-guanosine-3',5'-cyclic monophosphorothioate (Rp-8-pCPT-cGMPS)
      increased PE-induced proliferation of VSMC. SNAP, Sp-8-pCPT-cGMPS, and Rp-8-pCPT
      cGMPS did not affect the viability of VSMC. Calcineurin protein was decreased by
      63.1% and its activity was decreased by 59.7% in smooth muscle cells (SMC)
      pretreated with verapamil (Ver) and then stimulated by PE. In SMC pretreated with
      Ver, the absorbance of cells stimulated by PE decreased by 22.0% and was further
      inhibited by the additional treatment of SNAP and Sp-8-pCPT-cGMPS. In SMC
      pretreated with cyclosporin A (CsA), the absorbance of cells stimulated by PE
      decreased by 36.7%, but could not be further altered by the additional treatment
      of SNAP, Sp-8-pCPT-cGMPS, and Rp-8-pCPT-cGMPS. In addition, Ver inhibited PE
      induced intracellular Ca2+ variations, which could be further inhibited by SNAP
      and Sp-8-pCPT-cGMPS, but not by Rp-8-pCPT-cGMPS. Moreover, the increase in
      calcineurin activity induced by PE was inhibited by SNAP and Sp-8-pCPT-cGMPS, but
      was promoted by Rp-8-pCPT-cGMPS. CONCLUSION: NO/PKG regulates calcineurin
      activity via the modulation of intracellular Ca2+ concentration, and thus
      partially inhibits the proliferation of VSMC without affecting their viability.

PMID- 15715930
TI  - Structural comparisons of meptazinol with opioid analgesics.
AB  - AIM: To investigate the mechanism of action of a potent analgesic, (+/-)
      meptazinol. METHODS: The structures of meptazinol enantiomers were compared with
      opioid pharmacophore and tramadol. RESULTS: Neither enantiomer of meptazinol
      fitted any patterns among the opioid pharmacophore and tramadol, although they
      did share some structural and pharmacological similarities. However, the
      structure superpositions implied that both enantiomers of meptazinol might share
      some similar analgesic mechanisms with typical opiate analgesics. CONCLUSION:
      Meptazinol should have a different mechanism of action to known analgesics, which
      would be helpful in further investigations of meptazinol in the search for non
      addictive analgesics.

PMID- 15715931
TI  - Development of a complex scintillation proximity assay for high-throughput
      screening of PPARgamma modulators.
AB  - AIM: To develop a complex high-throughput screening (HTS) assay based on
      scintillation proximity assay (SPA) technology for identification of novel
      peroxisome proliferator-activated receptor gamma (PPARgamma) modulators. METHODS:
      Full-length PPARgamma and retinoid X receptor alpha (RXRalpha), biotinylated PPAR
      response element (PPRE), [3H]BRL49653 and streptavidin-coated FlashPlate or
      microbead were used to develop an HTS assay based on SPA technology. This 'ABCDE'
      method was validated against conventional hydroxyapatite (HA) assay and applied
      to large-scale screening of 16,000 synthetic compounds and natural product
      extracts. RESULTS: (1) IC50 values of positive control compounds (BRL49653 and
      troglitazone) obtained from the 'ABCDE' method and HA assay were comparable and
      consistent with those reported elsewhere; (2) Approximately 178 compounds,
      showing more than 70% competitive inhibition on BRL49653 binding to PPARgamma,
      were identified initially by the 'ABCDE' method (microbead); (3) Secondary
      screening using FlashPlate and cross-reactivity studies with RARalpha, beta,
      gamma and RXRalpha,beta, gamma confirmed that 12 compounds possessed specific
      PPARgamma binding properties including 2 with IC50 values less than 0.5
      micromol/L and novel chemical structures. CONCLUSIONS: The 'ABCDE' method using
      either FlashPlate or microbead, is a highly efficient, automatable, and robust
      tool to screen potential PPARgamma modulators in HTS setting. Its application may
      be expanded to other nuclear receptors that form heterodimers upon activation.

PMID- 15715929
TI  - Protective effects of cariporide on endothelial dysfunction induced by high
      glucose.
AB  - AIM: To explore the effects of cariporide, a selective sodium-hydrogen antiporter
      inhibitor, on endothelial dysfunction induced by high glucose. METHODS:
      Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium
      nitroprusside (SNP)-induced endothelium-independent relaxation and biochemical
      parameters including malondialdehyde (MDA), superoxide dismutase (SOD), and
      nitric oxide (NO) were measured in rat isolated aorta. RESULTS: A 6-h incubation
      of aortic rings with high glucose (44 mmol/L) resulted in a significant
      inhibition of EDR, but had no effects on endothelium-independent relaxation.
      After the 6-h incubation of aortic rings in the co-presence of cariporide (0.01,
      0.1, and 1 micromol/L) with high glucose, cariporide prevented the inhibition of
      EDR caused by high glucose in concentration-dependent manners. Similarly, high
      glucose decreased SOD activity and contents of NO, and increased MDA
      concentration in aortic tissue. Cariporide (1 micromol/L) significantly resisted
      the decrease of NO content and SOD activity, and elevation of MDA concentration
      caused by high glucose in aortic tissues. Mannitol (44 mmol/L) or cariporide (1
      micromol/L) alone had no effect on EDR, endothelium-independent relaxation and
      biochemical parameters. CONCLUSION: Cariporide significantly prevented
      endothelial dysfunction induced by high glucose. The mechanisms of endothelial
      dysfunction induced by high glucose may involve the activation of sodium-hydrogen
      antiporter and the generation of oxygen-free radicals, but it is not related to
      the change of osmolarity.

PMID- 15715932
TI  - Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B.
AB  - AIM: To examine the effects of Astragalus polysaccharide (APS), a component of an
      aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase
      1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction,
      and its potential role in the amelioration of insulin resistance. METHODS: Ten
      week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type II
      diabetes mellitus (TIIDM), were treated with APS (400 mg/kg p.o.) for 5 weeks.
      Insulin sensitivity was identified by the insulin-tolerance test. Further
      analyses on the possible changes in insulin signaling occurring in skeletal
      muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B
      activity was measured by an assay kit. RESULTS: The diabetic rats responded to
      APS with a significant decrease in body weight, plasma glucose, and improved
      insulin sensitivity. The activity and expression of PTP1B were elevated in the
      skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target
      tissues was diminished. APS reduced both PTP1B protein level and activity in the
      muscle, but not in the liver of TIIDM rats. Insulin-induced tyrosine
      phosphorylation of the IR beta-subunit and insulin receptor substrate-1 (IRS-1)
      were increased in the muscle, but not in the liver of APS-treated TIIDM rats.
      There was no change in the activity or expression of PTP1B in APS-treated normal
      rats, and blood insulin levels did not change in TIIDM rats after treatment with
      APS. CONCLUSION: APS enables insulin-sensitizing and hypoglycemic activity at
      least in part by decreasing the elevated expression and activity of PTP1B in the
      skeletal muscles of TIIDM rats.

PMID- 15715933
TI  - Changes of 5-lipoxygenase pathway and proinflammatory mediators in cerebral
      cortex and lung tissue of sensitized rats.
AB  - AIM: To explore the change of 5-lipoxygenase (5-LO) pathway expression and
      proinflammatory mediators level of lung tissue and cerebral cortex, and the
      possible regulatory mechanism through central nervous 5-LO pathways to pulmonary
      inflammatory status in antigen repeated challenged rats. METHODS: Four groups of
      rats were treated as control, asthma model, asthma model treatment with
      dexamethasone (DXM, 0.5 mg/kg, i.p.) and ketotifen (5 mg/kg, i.g.). Tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-4, interferon (IFN)-gamma, and
      nitric oxide (NO) were detected by ELISA kits. The mRNA expression of 5-LO and
      LTA4-hydrolase (LTA4-H) was analyzed by reverse transcription-polymerase chain
      reaction (RT-PCR), and the protein content of 5-LO was measured by Western blot.
      RESULTS: Increase of TNF-alpha, IL-4, NO level, and decrease of IFN-gamma level
      in bronchoalveolar lavage fluid (BALF) and cerebral cortex in sensitized rats
      were shown after repeated antigen challenge. The expression of 5-LO and LTA4-H
      mRNA, and 5-LO protein levels were increased in lung tissue and cerebral cortex
      in asthma rats. In comparison with the asthma model, DXM significantly inhibited
      the increase of cytokine levels and the expression of 5-LO pathway enzyme
      (P<0.05). Ketotifen also inhibited the increase of TNF-alpha level and 5-LO
      pathway enzyme expression in lung and cerebral cortex, but had no effect on the
      level of NO, IL-4, and IFN-gamma. CONCLUSION: The correlative increase of 5-LO
      pathway enzyme expression and proinflammatory mediators of brain may have a
      regulatory effect on pulmonary inflammation in asthma.

PMID- 15715934
TI  - Diethyldithiocarbamate inhibits iNOS expression in human lens epithelial cells
      stimulated by IFN-gamma and LPS.
AB  - AIM: To investigate the biological activity of human lens epithelial cells (HLEC)
      in producing inducible nitric oxide synthase (iNOS) and nitric oxide (NO), and to
      assesse the effect of diethyldithiocarbamate (DDC) on iNOS mRNA levels and
      expression of NOS. METHODS: The human lens epithelial cell line SRA 01/04 was
      used in this experiment. Semi-quantitative reverse transcription polymerase chain
      reaction (RT-PCR) and Western blotting were used to detect, respectively, iNOS
      mRNA expression and protein production. RESULTS: A costimulation by interferon
      gamma (IFN-gamma) and lipopolysaccharide (LPS) was necessary for iNOS expression
      in HLEC. The expression of iNOS was significantly reduced in a dose-dependent
      manner by adding DDC from 10 micromol/L to 1 mmol/L. CONCLUSION: The expression
      of iNOS in HLEC needs co-stimulation with IFN-gamma and LPS and it is inhibited
      by DDC.

PMID- 15715935
TI  - Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2
      inhibited proliferation of DU-145 cells.
AB  - AIM: To investigate the effect of antisense oligodeoxynucleotides (ASODN)
      targeting Pim-2 on cell proliferation of DU-145 cells. METHODS: Three ASODN
      targeting Pim-2 were designed and synthesized. After transfection with ASODN,
      cell proliferation was analyzed using an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. In
      addition, Pim-2 mRNA, protein levels, and cell cycles were examined. RESULTS: The
      ASODN designed and synthesized by our laboratory significantly reduced Pim-2 mRNA
      level and protein content in DU-145 cells. After transfection with ASODN for 48
      h, a marked reduction in cell viability was observed in DU-145 cells in a dose
      dependent manner. No remarkable apoptosis occurred in cells treated with ASODN
      compared with control cells. However, it should be noted that G1 phase arrest was
      clearly observed in ASODN-treated cells. CONCLUSION: ASODN targeting Pim-2
      resulted in a marked reduction in DU-145 cell proliferation, and induction of G1
      phase cell cycle arrest is one of the important mechanisms for ASODN to reduce
      cell growth. Moreover, antisense inhibition of Pim-2 expression provides a new
      promising therapy target for prostate cancer.

PMID- 15715936
TI  - Effects of spider Macrothele raven venom on cell proliferation and cytotoxicity
      in HeLa cells.
AB  - AIM: To examine the effect of venom from the spider Macrothele raven on cell
      proliferation and cytotoxicity in human cervical carcinoma, HeLa cells. METHODS:
      Morphological and biochemical signs of apoptosis appeared using acridine orange
      ethidium bromide (AO/EB) staining. Marked morphological changes in HeLa cells
      after treatment with spider venom were observed using scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). Cell proliferation
      and cytotoxicity were determined by [methyl-3H] thymidine assay ([3H]TdR) and
      lactate dehydrogenase (LDH) release, respectively. DNA fragmentation and cell
      cycle distribution were monitored using flow cytometry. In addition, Western blot
      analysis was used to evaluate the level of caspase-3 expression. In vivo
      examination of the inhibition of the size of tumors in nude mice treated with
      spider venom was measured. RESULTS: Marked morphological changes were observed
      using AO/EB staining, SEM and TEM assay. Spider venom at concentrations of 10-40
      mg/L caused dose- and time-dependent inhibition of HeLa cell proliferation. The
      ratio of apoptosis and necrosis increased. The activity of caspase-3 was
      upregulated after spider venom treatment. In vivo study of tumor size revealed
      that tumors significantly decreased in size from controls to tumors treated for 3
      weeks with spider venom (P<0.05). CONCLUSION: The inhibition of HeLa cells by the
      venom of the spider Macrothele raveni was carried out in three ways: induction of
      apoptosis, necrosis of toxicity damage and direct lysis. Spider venom is a novel
      anti-tumor material both in vitro and in vivo.

PMID- 15715937
TI  - Inhibition of STAT3 expression by siRNA suppresses growth and induces apoptosis
      in laryngeal cancer cells.
AB  - AIM: To determine the inhibitory effect of the synthetic STAT3 siRNA on the
      expression of STAT3 gene in human laryngeal cancer cell lines Hep2 and to
      investigate the effect of STAT3 siRNA on growth and apoptosis in Hep2 cells.
      METHODS: A pair of DNA templates coding siRNA against STAT3-mRNA was synthesized
      to reconstruct plasmid of pSilencer1.0-U6 siRNA-STAT3. Hep2 cells were
      transfected with RPMI-1640 media (untreated), plasmid (empty), and STAT3 siRNA,
      respectively. Northern blot and Western blot analysis of STAT3 and pTyr-STAT3
      expression in Hep2 cells and Western blot analysis of Bcl-2 expression in the
      Hep2 cell was performed 72 h after transfection. MTT, flow cytometry, and AO/EB
      assay were used for determination of cells proliferation and apoptosis in Hep2
      cells. RESULTS: pTyr-STAT3 was markedly expressed in untreated Hep2 cells and the
      vector-treated Hep2 cells, whereas pTyr-STAT3 expression was significantly
      reduced in STAT3 siRNA-transfected Hep2 cells, indicating that STAT3 siRNA
      inhibited the activity of STAT3. Transfection of Hep2 cells with STAT3 siRNA
      significantly inhibited STAT3 expression at both mRNA and protein level in Hep2
      cells and the inhibition was characterized by time-dependent transfection.
      Treatment of Hep2 cells with STAT3 siRNA resulted in dose-dependent growth
      inhibition of Hep2, this significantly increased apoptotic cell rate, and
      decreased Bcl-2 expression level in Hep2 cells. STAT3 siRNA had an effect on
      induction of either early or late stage apoptosis. CONCLUSION: This study
      demonstrates that STAT3 siRNA effectively inhibits STAT3 gene expression in Hep2
      cells leading to growth suppression and induction of apoptosis in Hep2 cells. The
      use of siRNA technique may provide a novel therapeutic approach to treat
      laryngeal cancer and other malignant tumors expressing constitutively activated
      STAT3.

PMID- 15715939
TI  - Transforming growth factor-beta : biology and clinical relevance.
AB  - Transforming growth factor-beta is a pleiotropic growth factor that has
      enthralled many investigators for approximately two decades. In addition to many
      reports that have clarified the basic mechanism of transforming growth factor
      beta signal transduction, numerous laboratories have published on the clinical
      implication/application of transforming growth factor-beta . To name a few,
      dysregulation of transforming growth factor-beta signaling plays a role in
      carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we
      will review these clinical implications of transforming growth factor-beta .

PMID- 15715938
TI  - Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to
      CYP2C19 genotype in healthy Chinese subjects.
AB  - AIM: To investigate whether the pharmacodynamics and pharmacokinetics of
      rabeprazole are dependent on CYP2C19 genotype status in healthy Chinese Han
      subjects. METHODS: The CYP2C19 genotype status of healthy Chinese Han volunteers
      was determined using the polymerase chain reaction-restriction fragment length
      polymorphism method. Twenty healthy subjects volunteered to participate in the
      study. There were seven homozygous extensive metabolizers (homEM), six
      heterozygous extensive metabolizers (hetEM), and seven poor metabolizers (PM).
      All subjects were Helicobactor pylori-negative, which was determined by sero-logy
      and 13C-urea breath tests. Rabeprazole (20 mg) was taken orally once daily in the
      morning for 8 days, and intragastric pH values were monitored for 24 h by
      Digitrapper pH after day 1 (single dose) and day 8 (repeated dose). Meanwhile,
      blood samples were collected at various time-points for 24 h after
      administration. The serum concentrations of rabeprazole were measured using high
      performance liquid chromatography. RESULTS: The mean area under the curve (AUC)
      values for rabeprazole differed among the three different genotype groups, with a
      relative ratio of 1.0, 1.3, and 1.8 after a single dose and 1.0, 1.1, and 1.7
      after repeated doses in the homEM, hetEM, and PM groups, respectively. Mean AUC
      values for rabeprazole after a single dose and after repeated doses were
      significantly different between the homEM and PM groups, but not between the
      homEM and hetEM or hetEM and PM groups. No significant differences in
      intragastric pH median, pH>4 total time, and pH>4 time percentage of 24 h, were
      observed among the three different genotype groups after a single dose or after
      repeated doses of rabeprazole. CONCLUSION: In healthy Chinese Han subjects, the
      pharmacokinetics of rabeprazole are dependent on a certain degree on CYP2C19
      genotype status; however, the acid-inhibitory efficacy of rabeprazole is not
      influenced significantly by CYP2C19 genetic polymorphism.

PMID- 15715940
TI  - Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads.
AB  - Transforming Growth Factor (TGF)-beta family, including TGF-beta, bone
      morphorgenic protein (BMP), and activn, plays an important role in essential
      cellular functions such as proliferation, differentiation, apoptosis, tissue
      remodeling, angiognesis, immune responses, and cell adhesions. TGF-beta
      predominantly transmits the signals through serine/threonine receptor kinases and
      cytoplasmic proteins called Smads. Since the discovery of TGF-beta in the early
      1980s, the dysregulation of TGF-beta /Smad signaling has been implicated in the
      pathogenesis of human diseases. Among signal transducers in TGF-beta/Smad
      signaling, inhibitory Smads (I-Smads), Smad6 and Smad7, act as major negative
      regulators forming autoinhibitory feedback loops and mediate the cross-talking
      with other signaling pathways. Expressions of I-Smads are mainly regulated on the
      transcriptional levels and post-translational protein degradations and their
      intracellular levels are tightly controlled to maintain the homeostatic balances.
      However, abnormal levels of I-Smads in the pathological conditions elicit the
      altered TGF-beta signaling in cells, eventually causing TGF-beta-related human
      diseases. Thus, exploring the molecular mechanisms about the regulations of I
      Smads may provide the therapeutic clues for human diseases induced by the
      abnormal TGF-beta signaling.

PMID- 15715941
TI  - Endo-1,4-beta-xylanase B from Aspergillus cf. niger BCC14405 isolated in
      Thailand: purification, characterization and gene isolation.
AB  - During the screening of xylanolytic enzymes from locally isolated fungi, one
      strain BCC14405, exhibited high enzyme activity with thermostability. This fugal
      strain was identified as Aspergillus cf. niger based on its morphological
      characteristics and internal transcribed spacer (ITS) sequences. An enzyme with
      xylanolytic activity from BCC14405 was later purified and characterized. It was
      found to have a molecular mass of ca. 21 kDa, an optimal pH of 5.0, and an
      optimal temperature of 55 degrees C. When tested using xylan from birchwood, it
      showed K(m) and V(max) values of 8.9 mg/ml and 11,100 U/mg, respectively. The
      enzyme was inhibited by CuSO(4) EDTA, and by FeSO(4) The homology of the 20
      residue N-terminal protein sequence showed that the enzyme was an endo-1,4-beta
      xylanase. The full-length gene encoding endo-1,4-beta-xylanase from BCC14405 was
      obtained by PCR amplification of its cDNA. The gene contained an open reading
      frame of 678 bp, encoding a 225 amino acid protein, which was identical to the
      endo-1,4-a-xylanase B previously identified in A. niger.

PMID- 15715942
TI  - Single-base discrimination mediated by proofreading inert allele specific
      Primers.
AB  - The role of 3' exonuclease excision in DNA polymerization was evaluated for
      primer extension using inert allele specific primers with exonuclease-digestible
      ddNMP at their 3' termini. Efficient primer extension was observed in amplicons
      where the inert allele specific primers and their corresponding templates were
      mismatched. However, no primer-extended products were yielded by matched
      amplicons with inert primers. As a control, polymerase without proofreading
      activity failed to yield primer-extended products from inert primers regardless
      of whether the primers and templates were matched or mismatched. These data
      indicated that activation was undertaken for the inert allele specific primers
      through mismatch proofreading. Complementary to our previously developed SNP
      operated on/off switch, in which DNA polymerization only occurs in matched
      amplicon, this new mutation detection assay mediated by exo(+) DNA polymerases
      has immediate applications in SNP analysis independently or in combination of the
      two assays.

PMID- 15715943
TI  - Molecular cloning, identification and characteristics of a novel isoform of
      carbamyl phosphate synthetase I in human testis.
AB  - A gene coding a novel isoform of carbamyl phosphate synthetase I (CPS1) was
      cloned from a human testicular library. As shown by cDNA microarray
      hybridization, this gene was expressed at a higher level in human adult testes
      than in fetal testes. The full length of its cDNA was 3831 bp, with a 3149 bp
      open reading frame, encoding a 1050-amino-acid protein. The cDNA sequence was
      deposited in the GenBank (AY317138). Sequence analysis showed that it was
      homologous to the human CPS1 gene. The putative protein contained functional
      domains composing the intact large subunit of carbamoyl phosphate synthetase,
      thus indicated it has the capability of arginine biosynthesis. A multiple tissue
      expression profile showed high expression of this gene in human testis,
      suggesting the novel alternative splicing form of CPS1 may be correlated with
      human spermatogenesis.

PMID- 15715944
TI  - Possible mechanism underlying the antiherpetic activity of a proteoglycan
      isolated from the mycelia of Ganoderma lucidum in vitro.
AB  - GLPG (Ganoderma lucidum proteoglycan) was a bioactive fraction obtained by the
      liquid fermentation of the mycelia of Ganoderma lucidum, EtOH precipitation, and
      DEAE-cellulose column chromatography.GLPG was a proteoglycan with a carbohydrate:
      protein ratio of 10.4: 1. Its antiviral activities against herpes simplex virus
      type 1 (HSV-1) and type 2 (HSV-2) were investigated using a cytopathic inhibition
      assay. GLPG inhibited cell death in a dose-dependent manner in HSV-infected
      cells. In addition, it had no cytotoxic effect even at 2 mg/ml. In order to study
      the mode of action of the antiviral activity of GLPG, cells were treated with
      GLPG before, during, and after infection, and viral titer in the supernatant of
      cell culture 48 h post-infection was determined using a TCID((50)) assay. The
      antiviral effects of GLPG were more remarkable before viral treatment than after
      treatment. Although the precise mechanism has yet to be defined, our work
      suggests that GLPG inhibits viral replication by interfering with the early
      events of viral adsorption and entry into target cells. Thus, this proteoglycan
      appears to be a candidate anti-HSV agent.

PMID- 15715945
TI  - Construction of a transposon-mediated baculovirus vector Hanpvid and a new cell
      line for expressing barnase.
AB  - In this study we developed the transposon-mediated shuttle vector 'Hanpvid',
      which composed of HaNPV (Heliothis armigera nuclear polyhedrosis virus) genomic
      DNA and a transposon cassette from Bacmid of Bac-to-Bac system. Hanpvid
      replicates in E. coli in the same way as Bacmid and retains infective function in
      cotton bollworm cells (Hz-AM1). Using Hanpvid we constructed a recombinant virus,
      which could infect Hz-AM1 cells and generate recombinant HaNPV (rHa-Bar)
      containing the barnase gene, a ribonuclease gene from Bacillus amyloliquefaciens.
      Since the expression vector carrying barnase gene cannot replicate in the absence
      of barstar, a specific inhibitor of barnase, we constructed a new cotton bollworm
      cell line (AM1-NB) using the marker rescue method. In AM1-NB barstar was
      integrated into the cellular chromosome to sustain the replication of rHa-Bar. To
      screen out recombinant HaNPV for potential use as biopesticide, Hz-AM1 and AM1-NB
      cell lines were infected with rHa-Bar, respectively. The results obtained
      indicate that Viral progenies in AM1-NB were 23 and 160 times greater than those
      in Hz-AM1 48 h and 72 h after infection, respectively. With additional insertion
      of the polyhedron gene from AcNPV (Autographa californica nuclear polyhedrosis
      virus) into the Hanpvid genome, rHa-Bar regained the polyhedron phenotype and its
      pest-killing rate greatly improved. Toxic analysis showed that the lethal dosages
      (LD(50)) and the lethal time(s) (LT(50)) of rHa-Bar were reduced by 20 % and 30
      %, respectively, compared to wt-HaNPV in the third instar larvae of cotton
      bollworm. This study shows that in AM1-NB barnase can be effectively produced and
      used as pest-killing agent for the biological control of cotton pests.

PMID- 15715946
TI  - Cloning, expression and genomic organization of genes encoding major royal jelly
      protein 1 and 2 of the honey bee (Apis cerana).
AB  - Major Royal Jelly Protein cDNAs of Apis cerana (AcMRJP) were cloned and
      characterized. The open reading frames (ORFs) of the AcMRJP1 and AcMRJP2 genes
      were 1302 and 1392 nucleotides, encoding 433 and 463 amino acid residues,
      respectively. The sequence divergences between AcMRJP1 and AcMRJP2 and their
      corresponding protein families in A. mellifera were 0.0618 and 0.0934 at the
      nucleotide level and 0.0912 and 0.1438 at the protein level, respectively.
      Phylogenetic analysis supports the orthologous similarity between these proteins.
      The deduced amino acids indicated high essential amino acid contents of AcMRJP1
      and AcMRJP2 (47.5 and 44.8 %, respectively). The genomic organization of both
      AcMRJP1 and AcMRJP2 was determined. Both the AcMRJP1 (3663 bp) and AcMRJP2 (3963
      bp) genes contained six exons and five introns, where all boundaries conformed to
      the GT/AG rule. AcMRJP1 and AcMRJP2 cDNAs were cloned into pET17b, and both the
      recombinant (r) AcMRJP1 (47.9 kDa) and rAcMRJP2 (51.7 kDa) were expressed in the
      insoluble form. Western blot analysis and N-terminal sequencing of the
      solubilized proteins revealed successful expression of rAcMRJP1 and rAcMRJP2 in
      vitro. The yields of the purified rAcMRJP1 and rAcMRJP2 were approximately 20 and
      8 mg protein per liter of the flask culture, respectively.

PMID- 15715947
TI  - Inactivation of brain myo-inositol monophosphate phosphatase by pyridoxal-5'
      phosphate.
AB  - Myo-inositol monophosphate phosphatase (IMPP) is a key enzyme in the
      phosphoinositide cell-signaling system. This study found that incubating the IMPP
      from a porcine brain with pyridoxal-5'-phosphate (PLP) resulted in a time
      dependent enzymatic inactivation. Spectral evidence showed that the inactivation
      proceeds via the formation of a Schiff's base with the amino groups of the
      enzyme. After the sodium borohydride reduction of the inactivated enzyme, it was
      observed that 1.8 mol phosphopyridoxyl residues per mole of the enzyme dimer were
      incorporated. The substrate, myo-inositol-1-phosphate, protected the enzyme
      against inactivation by PLP. After tryptic digestion of the enzyme modified with
      PLP, a radioactive peptide absorbing at 210 nm was isolated by reverse-phase
      HPLC. Amino acid sequencing of the peptide identified a portion of the PLP
      binding site as being the region containing the sequence L-Q-V-S-Q-Q-E-D-I-T-X,
      where X indicates that phenylthiohydantoin amino acid could not be assigned.
      However, the result of amino acid composition of the peptide indicated that the
      missing residue could be designated as a phosphopyridoxyl lysine. This suggests
      that the catalytic function of IMPP is modulated by the binding of PLP to a
      specific lysyl residue at or near its substrate-binding site of the protein.

PMID- 15715948
TI  - Transcription, translation, and immunolocalization of ODVP-6E/ODV-E56 and p74
      proteins: two highly conserved ODV-associated envelope proteins of Choristoneura
      fumiferana Granulovirus.
AB  - Choristoneura fumiferana granulovirus (ChfuGV) infection results two types of
      enveloped virions: Occlusion-derived virus (ODV) and budded virus (BV).
      Structural proteins ODVP-6E/ODV-E56 and p74 are two major conserved ODV
      associated proteins that may be involved in the initiation of viral infection
      cycle in susceptible host insect larvae. This study presents the characterization
      of ChfuGV odvp-6e/odv-e56 and p74 transcription and translation as well as
      immunolocalization of these proteins in the occluded ChfuGV virion. Our results
      revealed that the transcription of odvp-6e/odv-e56 and p74 genes, both, start at
      24 hours post infection (h p.i.). Using monospecific polyclonal antibodies made
      against ODVP-6E/ODV-E56 and p74 we demonstrated that these proteins are both
      expressed late in infection (24 h p.i.). Immunogold labeling using antisera
      against ODVP-6E/ODV-E56 and p74 proteins demonstrated that ODVP-6E/ODV-E56 and
      p74 proteins are both associated with the ODV envelop of ChfuGV.

PMID- 15715949
TI  - Production and characterization of monoclonal antibodies against human
      ceruloplasmin.
AB  - Ceruloplasmin (CP) is the major plasma antioxidant and copper transport protein.
      Monoclonal antibodies (mAbs) against human CP were produced and characterized. A
      total of five hybridoma cell lines were established (CP2, CP10, CP20, CP25,
      CP30). From the epitope mapping analysis, two subgroups of mAbs recognize
      different peptide fragments were identified. When the purified CP was incubated
      with the mAbs, the ferroxidase activity of CP was inhibited up to a maximum 57 %.
      Immunoblotting with various tissue homogenates indicated that all the mAbs
      specifically recognize a single protein band of 130 kDa. They also appear to be
      extensively cross-reactive among different mammalian including human and avian
      sources. These results demonstrated that only one type of immunologically similar
      CP is present in all of the mammalian tissues including human. The CP mAbs could
      be of great benefit to design the diagnostic kit for CP-related diseases such as
      Wilson's disease.

PMID- 15715950
TI  - Association analysis of monocyte chemotactic protein-3 (MCP3) polymorphisms with
      asthmatic phenotypes.
AB  - The monocyte chemotactic protein-3 (MCP3), on chromosome 17q11.2-q12, is a
      secreted chemokine, which attracts macrophages during inflammation and
      metastasis. In an effort to discover additional polymorphism(s) in genes whose
      variant(s) have been implicated in asthma, we scrutinized the genetic
      polymorphisms in MCP3 to evaluate it as a potential candidate gene for asthma
      host genetic study. By direct DNA sequencing in twenty-four individuals, we
      identified four sequence variants within the 3 kb full genome including 1,000bp
      promoter region of MCP3; one in promoter region (-420T>C), three in intron
      (+136C>G, +563C>T, +984G>A) respectively. The frequencies of those four SNPs were
      0.020 (-420T>C), 0.038 (+136C>G), 0.080 (+563C>T), 0.035 (+984G>A), respectively,
      in Korean population (n = 598). Haplotypes, their frequencies and linkage
      disequilibrium coefficients (|D'|) between SNP pairs were estimated. The
      associations with the risk of asthma, skin-test reactivity and total serum IgE
      levels were analyzed. Using statistical analyses for association of MCP3
      polymorphisms with asthma development and asthma-related phenotypes, no
      significant signals were detected. In conclusion, we identified four genetic
      polymorphisms in the important MCP3 gene, but no significant associations of MCP3
      variants with asthma phenotypes were detected. MCP3 variation/haplotype
      information identified in this study will provide valuable information for future
      association studies of other allergic diseases.

PMID- 15715951
TI  - Identification of an antifungal chitinase from a potential biocontrol agent,
      Bacillus cereus 28-9.
AB  - Bacillus cereus 28-9 is a chitinolytic bacterium isolated from lily plant in
      Taiwan. This bacterium exhibited biocontrol potential on Botrytis leaf blight of
      lily as demonstrated by a detached leaf assay and dual culture assay. At least
      two chitinases (ChiCW and ChiCH) were excreted by B. cereus 28-9. The ChiCW
      encoding gene was cloned and moderately expressed in Escherichia coli DH5alpha.
      Near homogenous ChiCW was obtained from the periplasmic fraction of E. coli cells
      harboring chiCW by a purification procedure. An in vitro assay showed that the
      purified ChiCW had inhibitory activity on conidial germination of Botrytis
      elliptica, a major fungal pathogen of lily leaf blight.

PMID- 15715952
TI  - The mutation that makes Escherichia coli resistant to lambda P gene-mediated host
      lethality is located within the DNA initiator Gene dnaA of the bacterium.
AB  - Earlier, we reported that the bacteriophage lambda P gene product is lethal to
      Escherichia coli, and the E. coli rpl mutants are resistant to this lambda P gene
      mediated lethality. In this paper, we show that under the lambda P gene-mediated
      lethal condition, the host DNA synthesis is inhibited at the initiation step. The
      rpl8 mutation maps around the 83 min position in the E. coli chromosome and is 94
      % linked with the dnaA gene. The rpl8 mutant gene has been cloned in a plasmid.
      This plasmid clone can protect the wild-type E. coli from lambda P gene-mediated
      killing and complements E. coli dnaAts46 at 42 degrees C. Also, starting with the
      wild-type dnaA gene in a plasmid, the rpl-like mutations have been isolated by in
      vitro mutagenesis. DNA sequencing data show that each of the rpl8, rpl12 and
      rpl14 mutations has changed a single base in the dnaA gene, which translates into
      the amino acid changes N313T, Y200N, and S246T respectively within the DnaA
      protein. These results have led us to conclude that the rpl mutations, which make
      E. coli resistant to lambda P gene-mediated host lethality, are located within
      the DNA initiator gene dnaA of the host.

PMID- 15715953
TI  - The bacteriophage lambda DNA replication protein P inhibits the oriC DNA- and ATP
      binding functions of the DNA replication initiator protein DnaA of Escherichia
      coli.
AB  - Under the condition of expression of lambda P protein at lethal level, the oriC
      DNA-binding activity is significantly affected in wild-type E. coli but not in
      the rpl mutant. In purified system, the lambda P protein inhibits the binding of
      both oriC DNA and ATP to the wild-type DnaA protein but not to the rpl DnaA
      protein. We conclude that the lambda P protein inhibits the binding of oriC DNA
      and ATP to the wild-type DnaA protein, which causes the inhibition of host DNA
      synthesis initiation that ultimately leads to bacterial death. A possible
      beneficial effect of this interaction of lambda P protein with E. coli DNA
      initiator protein DnaA for phage DNA replication has been proposed.

PMID- 15715954
TI  - Dynamics of supercoiled and linear pBluescript II SK(+) Phagemids probed with a
      long-lifetime metal-ligand complex.
AB  - We extended the measurable time scale of DNA dynamics to microsecond using
      [Ru(phen)(2)(dppz)](2+)(phen = 1,10-phenanthroline, dppz=dipyrido[3,2-a:2',3'
      c]phenazine)(RuPD) , which displays a mean lifetime near 500 ns. To evaluate the
      usefulness of this luminophore (RuPD) for probing nucleic acid dynamics, its
      intensity and anisotropy decays when intercalated into supercoiled and linear
      pBluescript (pBS) II SK(+) phagemids were examined using frequency-domain
      fluorometry with a blue light-emitting diode (LED) as the modulated light source.
      The mean lifetime for the supercoiled phagemids (<tau> = 489.7 ns) was somewhat
      shorter than that for the linear phagemids (<tau> = 506.4 ns), suggesting a more
      efficient shielding from water by the linear phagemids. The anisotropy decay data
      also showed somewhat shorter slow rotational correlation times for supercoiled
      phagemids (997.2 ns) than for the linear phagemids (1175.6 ns). The slow and fast
      rotational correlation times appear to be consistent with the bending and
      torsional motions of the phagemids, respectively. These results indicate that
      RuPD can have applications in studies of both bending and torsional dynamics of
      nucleic acids.

PMID- 15715955
TI  - Expression of Cu/Zn SOD protein is suppressed in hsp 70.1 knockout mice.
AB  - Heat shock proteins (HSPs) are known to protect cells from oxidative stress and
      other types of injuries. We previously reported the neuroprotective effect of
      HSP70 following cerebral ischemia and reperfusion using hsp 70.1 knockout (KO)
      mice. However, the precise role of HSP70 in neuroprotection has not been
      established yet. The purpose of this study was to investigate the relationship
      between HSP70 and antioxidant enzymes using hsp 70.1 KO mice. The activities of
      both SOD-1 and SOD-2 were significantly decreased in hsp 70.1 KO mice than in the
      wild type (WT) littermates. SOD-1 protein level in the hsp 70.1 KO mice was lower
      than that of WT. We speculate that HSP70 might be involved in regulation of
      expression of SOD-1 at the level of transcription or by post-transcriptional
      modification.

PMID- 15715956
TI  - Characteristic of aromatic amino acid substitution at alpha 96 of hemoglobin.
AB  - Replacement of valine by tryptophan or tyrosine at position alpha96 of the alpha
      chain (alpha96Val), located in the alpha(1)beta(2) subunit interface of
      hemoglobin leads to low oxygen affinity hemoglobin, and has been suggested to be
      due to the extra stability introduced by an aromatic amino acid at the alpha96
      position. The characteristic of aromatic amino acid substitution at the alpha96
      of hemoglobin has been further investigated by producing double mutant r Hb
      (alpha42Tyr --> Phe, alpha96Val --> Trp). r Hb (alpha42Tyr --> Phe) is known to
      exhibit almost no cooperativity in binding oxygen, and possesses high oxygen
      affinity due to the disruption of the hydrogen bond between alpha42Tyr and
      beta99Asp in thealpha(1)beta(2) subunit interface of deoxy Hb A. The second
      mutation, alpha96Val -->Trp, may compensate the functional defects of r Hb
      (alpha42Tyr --> Phe), if the stability due to the introduction of trypophan at
      the alpha 96 position is strong enough to overcome the defect of r Hb (alpha42Tyr
      --> Phe). Double mutant r Hb (alpha42Tyr --> Phe, alpha96Val --> Trp) exhibited
      almost no cooperativity in binding oxygen and possessed high oxygen affinity,
      similarly to that of r Hb (alpha42Tyr --> Phe). (1)H NMR spectroscopic data of r
      Hb (alpha42Tyr --> Phe, alpha96Val --> Trp) also showed a very unstable deoxy
      quaternary structure. The present investigation has demonstrated that the
      presence of the crucible hydrogen bond between alpha 42Tyr and beta 99Asp is
      essential for the novel oxygen binding properties of deoxy Hb (alpha96Val -->
      Trp) .

PMID- 15715957
TI  - Oxidative damage of plasma proteins and lipids in epidemic dropsy patients:
      alterations in antioxidant status.
AB  - Epidemic dropsy is an acute food adulterant disease caused due to consumption of
      edible mustard oil contaminated with argemone oil. Our in vitro studies have
      shown that the toxicity of argemone oil is due to the production of reactive
      oxygen species. The present study was aimed to evaluate the development of
      oxidative stress in terms of oxidation of plasma proteins and lipids and its
      correlation to enzymatic and non-enzymatic antioxidants in epidemic dropsy
      patients. Total plasma protein and globulin contents were found to be
      significantly (P<0.05) enhanced with a concomitant decrease (P<0.05) in
      albumin/globulin ratio in dropsy patients when compared to controls. Total
      cholesterol, triglycerides, low density lipoprotein cholesterol and very low
      density lipoprotein cholesterol were found to be significantly (P<0.05) increased
      with a simultaneous decrease (51%) in high density lipoprotein cholesterol in
      dropsy patients. The oxidation of plasma proteins and lipids were substantially
      enhanced (162-175%) in dropsy patients when compared to controls. Further,
      significant (P<0.05) decrease in superoxide dismutase, catalase, glutathione
      reductase and glutathione-s-transferase with a concomitant increase (69%) in
      glutathione peroxidase activity was noticed in dropsy patients. A significant
      reduction in plasma total antioxidant capacity, alpha-tocopherol, glutathione,
      retinol and retinyl esters content was observed in dropsy patients when compared
      to healthy controls. The results suggest that there exists an unproportionate
      equilibrium between free radicals formation and enzymatic and non-enzymatic
      antioxidant scavengers, which may cause oxidative damage to proteins and lipids
      in dropsy patients.

PMID- 15715959
TI  - TNF signalings as pleiotropic gates in the liver.

PMID- 15715958
TI  - Cloning, sequencing and functional expression in Escherichia coli of the gene for
      a P-type Na(+)-ATPase of a facultatively anaerobic alkaliphile, Exiguobacterium
      aurantiacum.
AB  - Cloning and sequencing of the gene encoding a P-type Na(+)-ATPase of a
      facultatively anaerobic alkaliphile, Exiguobacterium aurantiacum, were conducted.
      The structural gene was composed of 2628 nucleotides. The deduced amino acid
      sequence (876 amino acid residues; Mr, 96,664) suggested that the enzyme
      possesses 10 membrane-spanning regions. When the amino acid sequences of the four
      putative membrane regions, M4, M5, M6 and M8, of BL77/1 ATPase were aligned with
      those of fungal Na(+)-ATPase, Na(+)/K(+)-ATPase, H(+)-ATPases and sarcoplasmic
      reticulum Ca(2+)-ATPase, it exhibited the highest homology with Ca(2+)-ATPase
      except M5 region. By the transformation of Escherichia coli with the expression
      vector (pQE30) containing the ATPase gene, the enzyme was functionally expressed
      in E. coli membranes.

PMID- 15715960
TI  - Identification of endothelial genes up-regulated in vivo.
AB  - We have used microarrays to identify genes that are selectively expressed in
      endothelial cells in vivo. Analysis of freshly isolated endothelial cells from
      the lungs and kidneys reveals that 350 out of the 10,000 genes represented on the
      microarrays were expressed at higher levels than by the corresponding parenchymal
      cells. Thirteen of these genes were identified both in the lung and kidney
      screens from a subset of about 5000 genes. Many of these genes are known to be
      specifically expressed in endothelial cells, but about 200 genes were potentially
      novel endothelial genes. The preferential endothelial expression of a selected
      group of these genes was confirmed by quantitative polymerase chain reaction or
      in situ mRNA hybridization. Comparison of the genes expressed in lung and kidney
      endothelia revealed numerous differences. Notably, genes encoding components of
      an ephrin signaling pathway were highly expressed in lung endothelial cells. In
      summary, the genes we have identified represent potentially new pan-endothelial
      and tissue-specific endothelial markers.

PMID- 15715961
TI  - CDK2/4 regulate retinoic acid-induced G1 arrest in hepatocellular carcinoma
      cells.
AB  - Retinoic acid (RA) is an important regulator of normal cellular proliferation and
      differentiation and suppressor of tumor growth by cell cycle arrest and
      apoptosis. Furthermore, RA showed a chemo-preventive activity in preclinical
      and/or clinical models of lung, head and neck, breast, and hepatocellular
      carcinoma (HCC). In this study, we examined the effect of RA on the proliferation
      of human HCC cells, in order to analyze its mode of action and, finally, we
      attempted to find a surrogate biomarker of RA for HCC chemopreventive treatment.
      Our findings suggested that the growth inhibition of RA in HCC cells differed
      according to G(1) phase delay by CDK2 or 4, finally induction of apoptosis. No
      correlation was found between RA sensitivity and the expression of nuclear
      retinoid receptors, such as RARs or RXRs in HCC cells. RA treatment caused cell
      cycle arrest at G(1) and decreased the expressions and activities of CDK2 or CDK4
      in RA-sensitive HepG2 and SNU354 cells. On the other hand, RA-resistant Hep3B and
      SNU449 cells progressed into the S/G(2)+M phase and showed increased CDK2 and
      CDK4 expression and activity. Since the inhibition of CDK2 or 4 activities
      resulted in sensitization of HCC cells to RA, the combination of RA and compounds
      of inhibiting CDKs such as UCN01 and flavopiridol might be a useful targeted
      therapy strategy for HCC.

PMID- 15715962
TI  - DaTrypsin, a novel clip-domain serine proteinase gene up-regulated during winter
      and summer diapauses of the onion maggot, Delia antiqua.
AB  - Diapause prepares insects and other arthropods to survive in harsh environments.
      To explore the molecular basis of winter (WD) and summer diapauses (SD), we
      screened for diapause-specific genes in the onion maggot, Delia antiqua, that
      diapauses as a pupa in both summer and winter. A diapause-induced transcript,
      DaTrypsin, was identified through differential display, and examined by Northern
      blot, quantitative real-time PCR and sequence analyses. The full-length cDNA,
      1379 bp long, encodes 384 a.a. with a molecular mass of 43,005 Da. The protein
      contains a 20-a.a. secretion peptide, followed by an amino-terminal clip domain
      and a carboxyl-terminal serine proteinase domain. With Ser, His and Asp as
      catalytic residues and Asp, Gly and Ser as specificity determinants, DaTrypsin is
      anticipated to be a trypsin-like enzyme. DaTrypsin transcription is up-regulated
      in both SD and WD pupae with higher mRNA levels during WD than SD. Heat shock
      further elevated gene transcription in both SD and WD pupae, whereas cold shock
      reduced DaTrypsin expression in SD pupae and had no significant effect on WD
      pupae. In SD pupae, DaTrypsin transcripts gradually build up during diapause, and
      after temperature shocks, whereas in WD pupae DaTrypsin mRNA levels are high at
      the beginning of diapause and immediately after a temperature shock and then
      gradually decrease with time. DaTrypsin represents the first serine proteinase
      gene expressed during diapause as well as the first gene up-regulated in both SD
      and WD. It may participate in the host's immune defense and/or maintain the
      developmental status in the diapausing pupae.

PMID- 15715963
TI  - U2552 methylation at the ribosomal A-site is a negative modulator of
      translational accuracy.
AB  - We have recently identified RrmJ, the first encoded protein of the rrmJ-ftsH heat
      shock operon, as being the Um(2552) methyltransferase of 23S rRNA, and reported
      that rrmJ-deficient strains exhibit growth defects, reduced translation rates and
      reduced stability of 70S ribosomes. U2552 is an ubiquitously methylated residue.
      It belongs to the A loop of 23S RNA which is an essential component of the
      ribosome peptidyltransferase centre and interacts directly with aminoacyl(A)-site
      tRNA. In the present study, we show that a lack of U2552 methylation, obtained in
      rrmJ-deficient mutants, results in a decrease in programmed +1 and -1
      translational frameshifing and a decrease in readthrough of UAA and UGA stop
      codons. The increased translational accuracy of rrmJ-deficient strains suggests
      that the interaction between aminoacyl-tRNA and U2552 is important for selection
      of the correct tRNA at the ribosomal A site, and supports the idea that
      translational accuracy in vivo is optimal rather than maximal, thus pointing to
      the participation of recoding events in the normal cell physiology.

PMID- 15715964
TI  - PLAUF is a novel P. lividus sea urchin RNA-binding protein.
AB  - Preliminary results have shown that various proteins bind long 3'UTR of the
      transcript for Paracentrotus lividus sea urchin H3.3 histone variant and are
      probably implicated in mRNA instability. In order to identify these RNA-binding
      proteins, we screened a lambda-ZAPII cDNA expression library prepared from
      poly(A) mRNA extracted from sea urchin embryos at blastula stage. We isolated a
      cDNA that codes for a novel RNA-binding protein homologous to rat and human AUF1
      family proteins and we refer to it as PLAUF. Proteins present in the whole lysate
      of the phages expressing PLAUF bound specifically in vitro the 3'UTR of the H3.3
      histone transcript. Northern blot analysis revealed three PLAUF transcripts that
      are already present in unfertilized eggs; during development their amount
      increased starting from 4-blastomere embryos and reached the plateau at blastula
      stage. While the transcription start point was unique, longer 3'UTRs were
      revealed by 3'RACE approach and further cDNA library screening. Moreover RT-PCR
      showed the presence of at least one alternative spliced mRNA that codes for a
      protein with different COOH terminus. The structure of the PLAUF gene was
      determined by screening a P. lividus sea urchin genomic library with the PLAUF
      cDNA as probe. Analysis of the positive clones showed that the PLAUF gene is
      split in 10 exons and 9 introns spanning a distance of about 10 kb. Moreover we
      demonstrated that the exon 9 was alternative spliced during mRNA processing.

PMID- 15715965
TI  - GCN5: a supervisor in all-inclusive control of vertebrate cell cycle progression
      through transcription regulation of various cell cycle-related genes.
AB  - Histone acetyltransferases (HATs) are involved in the acetylation of core
      histones, which is an important event for transcription regulation through
      alterations in the chromatin structure in eukaryotes. To clarify participatory in
      vivo roles of two such enzymes known as GCN5 and PCAF, we generated homozygous
      DT40 mutants, DeltaGCN5 and DeltaPCAF, devoid of two alleles of each of the GCN5
      and PCAF genes, respectively, with the help of gene targeting technique. While
      the PCAF-deficiency exhibited no effect on growth rate, the GCN5-deficiency
      caused delayed growth rate of DT40 cells. FACS analyses revealed not only that
      the number of cells in S phase decreased, but also that the cell cycle
      progression was suppressed at G1/S phase transition for DeltaGCN5. RT-PCR
      analyses revealed that the GCN5-deficiency exhibited opposite influences on
      transcriptions of G1/S phase transition-related genes, i.e. repressions for E2F
      1, E2F-3, E2F-4, E2F-6, DP-2, cyclin A, cyclin D3, PCNA, cdc25B and p107; and
      activations for p27, c-myc, cyclin D2 and cyclin G1. Similarly, the deficiency
      influenced oppositely transcriptions of apoptosis-related genes, i.e. decreased
      expression of bcl-xL and increased expression of bcl-2. Immunoblotting analyses
      using a number of anti-acetylated histone antisera revealed that the GCN5
      deficiency led to decreased acetylation levels of K16/H2B and K9/H3, and
      increased those of K7/H2A, K18/H3, K23/H3, K27/H3, K8/H4 and K12/H4. These
      results indicate that GCN5 preferentially acts as a supervisor in the normal cell
      cycle progression having comprehensive control over expressions of these cell
      cycle-related genes, as well as apoptosis-related genes, probably via alterations
      in the chromatin structure, mimicked by changing acetylation status of core
      histones, surrounding these widely distributed genes.

PMID- 15715966
TI  - Multiple novel isoforms of Trio are expressed in the developing rat brain.
AB  - Mammalian Trio is a multifunctional, multidomain Rho guanine nucleotide exchange
      factor (GEF) closely related to Kalirin. Trio is important for proper axon
      guidance in Drosophila, and mice lacking Trio exhibit both skeletal muscle and
      neuronal disorders. Full length mammalian Trio and Kalirin both consist of a
      Sec14P-like domain, several spectrin-like domains, two Rho GEF domains each
      containing a Dbl-homology (DH) and a pleckstrin-homology (PH) domain, two src
      homology 3 domains (SH3), Ig/fibronectin-like domains (Ig/FN), and a kinase
      domain. We have previously described multiple isoforms of Kalirin derived through
      alternative splicing and multiple transcription start sites, but multiple
      isoforms of Trio containing different functional domains have not been described.
      Using a new antibody directed against the spectrin-like region of rat Trio
      coupled with reverse transcription PCR and cDNA sequencing, we have identified 4
      novel isoforms of Trio expressed in rat cortex and cerebellum. Two isoforms, Trio
      9S and Trio 9L, are derived through alternative splicing of Trio exon 48 and are
      abundantly expressed in rat brain. Trio 8 is expressed in postnatal day 30 and
      adult cerebellum, but not in cortex or skeletal muscle. Trio/duet is expressed in
      adult cortex and cerebellum. In the rat brain, each of these Trio isoforms is
      expressed at a higher level than full length Trio.

PMID- 15715967
TI  - Identification of NOM1, a nucleolar, eIF4A binding protein encoded within the
      chromosome 7q36 breakpoint region targeted in cases of pediatric acute myeloid
      leukemia.
AB  - Proteins that contain the recently described MIF4G and/or MA3 domains function in
      translation, cell growth, proliferation, transformation, and apoptosis. Examples
      of MIF4G/MA3 containing proteins and their functions include eIF4G, which serves
      as a scaffold for assembly of factors required for translation initiation,
      programmed cell death protein 4 (Pdcd4) that inhibits translation and functions
      as a tumor suppressor, and NMD2, which is essential for nonsense-mediated mRNA
      decay. MIF4G and MA3 domains serve as binding sites for one or more isoforms of
      the eIF4A family of ATP-dependent DEAD-box RNA helicases that are required for
      translation and for nonsense-mediated decay. In this report, we describe the
      characterization of a novel MIF4G/MA3 family member called NOM1 (nucleolar
      protein with MIF4G domain 1) that was identified at the chromosome 7q36
      breakpoint involved in 7;12 translocations associated with certain acute
      leukemias of childhood. NOM1, which includes a previously described EST called
      c7orf3, encodes a ubiquitously expressed transcript composed of 11 exons and an
      approximately 3 kb 3' UTR that contains several Alu repeats. The predicted NOM1
      protein contains one MIF4G domain and one MA3 domain and, consistent with data
      obtained with other MIF4G/MA3 proteins, interacts with members of the eIF4A
      family of helicases. Database searches reveal that NOM1 homologs exist in several
      organisms and that at least two of these are essential genes. Finally, like its
      Saccharomyces cerevisiae homolog Sgd1p, NOM1 localizes predominantly to the
      nucleolus. These data demonstrate that NOM1 is a new member of the MIF4G/MA3
      family of proteins and suggest that it may provide an essential function in
      metazoans.

PMID- 15715968
TI  - Expression and purification of the catalytic domain of human vascular endothelial
      growth factor receptor 2 for inhibitor screening.
AB  - Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen,
      can act in tumor-induced angiogenesis by binding to specific receptors on the
      surface of endothelial cells. One such receptor, VEGFR-2/KDR, plays a key role in
      VEGF-induced angiogenesis. Here, we expressed the catalytic domain of VEGFR-2 as
      a soluble active kinase using Bac-to-Bac expression system, and investigated
      correlations between VEGFR-2 activity and enzyme concentration, ATP
      concentration, substrate concentration and divalent cation type. We used these
      data to establish a convenient, effective and non-radioactive ELISA screening
      technique for the identification and evaluation of potential inhibitors for VEGFR
      2 kinase. We screened 200 RTK target-based compounds and identified one (TKI-31)
      that potently inhibited VEGFR-2 kinase activity (IC50=0.596 microM). Treatment of
      NIH3T3/KDR cells with TKI-31 blocked VEGF-induced phosphorylation of KDR in a
      dose-dependent manner. Moreover, TKI-31 dose-dependently suppressed HUVEC tube
      formation. Thus, we herein report a novel, efficient method for identifying VEGFR
      2 kinase inhibitors and introduce one, TKI-31, that may prove to be a useful new
      angiogenesis inhibitor.

PMID- 15715969
TI  - Plasma and whole blood pharmacokinetics of topiramate: the role of carbonic
      anhydrase.
AB  - Topiramate (TPM) is a broad-spectrum antiepileptic drug with various mechanisms
      of action including an inhibitory effect on some isozymes of carbonic anhydrase
      (CA). Binding to CA-I and CA-II, which are highly concentrated in erythrocytes,
      may affect drug pharmacokinetics. Consequently, the objectives of this study
      were: (a) to comparatively assess TPM pharmacokinetics in healthy subjects, based
      on plasma and whole blood data, by simultaneously measuring TPM concentrations in
      plasma and whole blood following different therapeutic doses; (b) to rigorously
      establish the affinity of TPM for CA-I and CA-II in order to gain insight into
      how binding to these isozymes in erythrocytes influences TPM pharmacokinetics.
      TPM (100, 200 and 400 mg, single dose) was given in a randomized three-way
      crossover design to 27 healthy subjects and the drug concentrations in plasma and
      whole blood were simultaneously measured for 168 h after dosing. The
      pharmacokinetics of TPM in plasma was linear, but TPM clearance from whole blood
      increased with increasing dose. At low therapeutic concentrations, the blood-to
      plasma ratio for TPM decreased from 8 to 2 as its concentration increased,
      indicating a substantial and saturable binding of TPM to erythrocytes. The
      kinetics (dissociation binding constant -Kd and maximum binding rate -Bmax) of
      the binding of TPM to erythrocytes was determined from the measured
      concentrations of TPM in whole blood and plasma. This analysis indicated the
      existence of two binding sites with Kd values of 0.54 and 140 microM, and Bmax
      values of 22 and 124 micromol/L of erythrocyte volume, respectively. These Bmax
      values are similar to literature values for the molar concentration of human CA
      II (14-25 micromol/L) and CA-I (115-125 micromol/L). TPM inhibition constant (Ki)
      values for the inhibition of purified human CA obtained using assays based on CO2
      hydration or 4-nitrophenylacetate hydrolysis were 0.62 and 0.49 microM for CA-II,
      and 91 and 93 microM for CA-I. The results of these studies indicate that
      virtually all of the binding of TPM to erythrocytes is attributable to CA-I and
      CA-II. Because CA-I and CA-II are highly concentrated in erythrocytes, a large
      portion of TPM in whole blood is bound and serves as a depot. This contributes to
      the lower oral clearance (CL/F), apparent volume of distribution (Vss/F) and
      longer half-life (t(1/2)) that TPM has in blood compared to the CL/F, Vss/F and
      t(1/2), estimated from plasma data. The difference between TPM blood and plasma
      pharmacokinetics was more profound at low doses (< or = 100 mg/day).

PMID- 15715970
TI  - In vivo and in vitro effect of Capsicum annum proteinase inhibitors on
      Helicoverpa armigera gut proteinases.
AB  - Two proteinase inhibitors (PIs), CapA1 and CapA2, were purified from Capsicum
      annum Linn. Var. Phule Jyoti leaves and assessed for their in vitro and in vivo
      activity against Helicoverpa armigera gut proteinases (HGPs). Both the inhibitors
      exhibited molecular weights of about 12 kDa with inhibitory activity against
      bovine trypsin and chymotrypsin indicating presence of probable two-inhibitor
      repeats of PIN II family. CapA1 and CapA2 inhibited 60-80% HGP (azocaseinolytic)
      activity of fourth instar larvae feeding on various host plants while 45-65%
      inhibition of HGP activity of various instars (II to VI) larvae reared on
      artificial diet. The partial purification of HGP isoforms, their characterization
      with synthetic inhibitors and inhibition by C. annum PIs revealed that most of
      the trypsin-like activity (68-91%) of HGPs was sensitive to C. annum PIs while 39
      85% chymotrypsin-like activity of HGPs was insensitive to these inhibitors. The
      feeding of C. annum leaf extracts and two purified PIs in various doses to H.
      armigera larvae for two successive generations through artificial diet
      demonstrated their potential in inhibiting larval growth and development, delay
      in pupation period and dramatic reduction in fecundity and fertility. This is the
      first report-demonstrating efficacy of C. annum PIs against insect gut
      proteinases as well as larval growth and development of H. armigera.

PMID- 15715972
TI  - A human T-cell lymphotropic virus type-1 (HTLV-1) carrier complicated with
      various autoimmune diseases including primary biliary cirrhosis.
AB  - A 47-year-old woman with primary biliary cirrhosis and scleroderma was examined
      at our hospital for a 1-week history of non-resolving fever, arthralgia, myalgia,
      muscle weakness and fatigue. A diagnosis of systemic lupus erythematosus was made
      based on arthralgia, low leukocyte count, low lymphocyte count, low serum
      concentration of complements, positive anti-nuclear antibody and positive anti
      double-strand-DNA antibody. She was negative for anti-U1RNP antibody, but
      positive for anti-Jo1 antibody, and her initial serum concentration of creatine
      phosphokinase was elevated. We diagnosed her as having overlap syndrome with
      scleroderma, systemic lupus erythematosus and possible polymyositis associated
      with primary biliary cirrhosis. Prednisolone rapidly improved her symptoms.
      Lobulated leukocytes were observed in her peripheral blood specimen. She was
      positive for anti-HTLV-1 antibody, but Southern blot hybridization did not
      confirm monoclonal integration of HTLV-I proviral DNA in her peripheral blood.
      This suggests the possibility of a relationship between HTLV-1 infection and
      various autoimmune disorders including primary biliary cirrhosis.

PMID- 15715971
TI  - Molecular cloning and characterization of calmodulin genes in young oak seedlings
      (Quercus petraea L.) during early flooding stress.
AB  - As part of an integrated study on the molecular response of woody plants to
      flooding, three CaM genes were isolated from oak seedlings (Quercus petraea
      Liebl.) and characterized. QpCaM-1 was almost exclusively expressed in roots,
      whereas QpCaM-2 and -3 were more evenly distributed throughout the plant. The
      present paper documents the differential expression of these genes during
      hypoxia.

PMID- 15715973
TI  - Liver injury induced by lipopolysaccharide is mediated by TNFR-1 but not by TNFR
      2 or Fas in mice.
AB  - Endotoxemia causes liver injury in which tumor necrosis factor (TNF)-alpha plays
      a significant role by inducing hepatic apoptosis. We here examined if such
      apoptosis is strictly dependent on TNF-alpha and which type of TNF receptor
      (TNFR) is involved, employing TNFR-1- and -2-knockout mice. Lipopolysaccharide
      (LPS) dose-dependently induced liver injury in both wild-type (WT) and TNFR-2
      knockout mice as indicated by plasma ALT activities, whereas the injury was
      absent in TNFR-1-knockout mice. Similarly, apoptotic hepatocyte death was
      observed in WT and TNFR-2-knockout mice after LPS-injection, but not in TNFR-1
      knockout mice. Plasma levels of TNF-alpha, interleukin (IL)-6, IL-10 and
      interferon-gamma as well as hepatic TNF-alpha levels increased equally in mice
      with either genotype after LPS-injection. LPS also enhanced equally the mRNA
      expression of Fas but not Fas ligand irrespective of either genotype, as measured
      by RNase protection assay. These findings suggest that apoptotic liver injury
      induced by LPS depends on TNF-alpha signaling through TNFR-1 but not via TNFR-2
      or Fas-Fas ligand pathway.

PMID- 15715974
TI  - Lipid rafts and their roles in T-cell activation.
AB  - Lipid rafts are defined as detergent-resistant membrane microdomains of specific
      lipid and protein composition. They are involved in many aspects of cell biology,
      including T-cell activation and immunoreceptor signaling. This review discusses
      current controversies around lipid rafts and summarizes recent developments in
      the area.

PMID- 15715975
TI  - Severe and fatal central nervous system disease in humans caused by Baylisascaris
      procyonis, the common roundworm of raccoons: a review of current literature.
AB  - Baylisascaris procyonis, a parasitic infection of raccoons, causes severe
      neurologic disease in humans when infective eggs from raccoon feces are ingested.
      Definitive diagnosis is challenging, but can be made by isolation of larvae in
      brain biopsy or exclusion of other potential causes of eosinophilic
      meningoencephalitis. Prevention efforts are critical due to the lack of effective
      treatment.

PMID- 15715976
TI  - The evolutionary history of the CCR5-Delta32 HIV-resistance mutation.
AB  - The CCR5 chemokine receptor is exploited by HIV-1 to gain entry into CD4+ T
      cells. A deletion mutation (Delta32) confers resistance against HIV by
      obliterating the expression of the receptor on the cell surface. Intriguingly,
      this allele is young in evolutionary time, yet it has reached relatively high
      frequencies in Europe. These properties indicate that the mutation has been under
      intense positive selection. HIV-1 has not exerted selection for long enough on
      the human population to drive the CCR5-Delta32 allele to current frequencies,
      fueling debate regarding the selective pressure responsible for rise of the
      allele. The allele exists at appreciable frequencies only in Europe, and within
      Europe, the frequency is higher in the north. Here we review the population
      genetics of the CCR5 locus, the debate over the historical selective pressure
      acting on CCR5-Delta32, the inferences that can potentially be drawn from the
      geographic distribution of CCR5-Delta32 and the role that other genetic
      polymorphisms play in conferring resistance against HIV. We also discuss parallel
      evolution that has occurred at the CCR5 locus of other primate species. Finally,
      we highlight the promise that therapies based on interfering with the CCR5
      receptor could have in the treatment of HIV.

PMID- 15715977
TI  - Candida albicans double-stranded DNA can participate in the host defense against
      disseminated candidiasis.
AB  - In the present work, we studied the in vitro immunomodulatory properties of
      double-stranded Candida albicans DNA and its protective effect in murine
      disseminated candidiasis. DNA induced the production of TNF-alpha by peritoneal
      macrophages and splenocytes in vitro through a chloroquine-dependent mechanism.
      Yeast DNA acted synergistically with IFN-gamma in triggering the secretion of
      nitric oxide by macrophages and enabled them to stimulate the proliferation of T
      cells in response to soluble anti-CD3. The effect of DNA on splenocytes is
      associated with an enhanced synthesis of IFN-gamma, IL-2 and IL-10. In vivo, DNA
      decreased the mortality and lowered the kidney contamination in mice
      intraperitoneally inoculated with C. albicans simultaneously with an increase in
      the specific proliferative response and cytokine production. The present results
      indicate that C. albicans DNA can provide protection against disseminated
      infection.

PMID- 15715978
TI  - A SCA7 CAG/CTG repeat expansion is stable in Drosophila melanogaster despite
      modulation of genomic context and gene dosage.
AB  - CAG and CTG repeat expansions are the cause of at least a dozen inherited
      neurological disorders. In these so-called "dynamic mutation" diseases, the
      expanded repeats display dramatic genetic instability, changing in size when
      transmitted through the germline and within somatic tissues. As the molecular
      basis of the repeat instability process remains poorly understood, modeling of
      repeat instability in model organisms has provided some insights into potentially
      involved factors, implicating especially replication and repair pathways. Studies
      in mice have also shown that the genomic context of the repeat sequence is
      required for CAG/CTG repeat instability in the case of spinocerebellar ataxia
      type 7 (SCA7), one of the most unstable of all CAG/CTG repeat disease loci. While
      most studies of repeat instability have taken a candidate gene approach, unbiased
      screens for factors involved in trinucleotide repeat instability have been
      lacking. We therefore attempted to use Drosophila melanogaster to model expanded
      CAG repeat instability by creating transgenic flies carrying trinucleotide repeat
      expansions, deriving flies with SCA7 CAG90 repeats in cDNA and genomic context.
      We found that SCA7 CAG90 repeats are stable in Drosophila, regardless of context.
      To screen for genes whose reduced function might destabilize expanded CAG repeat
      tracts in Drosophila, we crossed the SCA7 CAG90 repeat flies with various
      deficiency stocks, including lines lacking genes encoding the orthologues of flap
      endonuclease-1, PCNA, and MutS. In all cases, perfect repeat stability was
      preserved, suggesting that Drosophila may not be a suitable system for
      determining the molecular basis of SCA7 CAG repeat instability.

PMID- 15715979
TI  - Genomic analysis of the Microphthalmia locus and identification of the MITF
      J/Mitf-J isoform.
AB  - The deafness-pigmentary disorder Waardenburg Syndrome Type 2 is caused by
      mutations in the human Microphthalmia-associated transcription factor (MITF)
      gene. Multiple related deafness-pigmentary disorders result from mutations in
      genes that regulate MITF expression or its activity. Similarly in mouse,
      homozygous mutations in the Mitf gene disrupt the development of melanocytes as
      well as retinal pigment epithelial (RPE) cells, osteoclasts, mast cells, and NK
      cells. Because abnormalities in Mitf/MITF function are associated with numerous
      inherited disorders of mouse and man, a detailed understanding of its gene
      structure is important for both diagnostic and structure/function analyses. While
      at least eight distinct isoforms of MITF/Mitf have been identified to date, each
      differing in their promoter and initial exon usage, the positions of these exons
      and their order within the locus have yet to be fully defined. In this study, we
      provide a detailed description of the MITF/Mitf locus, identify corresponding
      human and mouse isoforms, and utilize an informatics-based approach to identify a
      novel ninth MITF/Mitf isoform, MITF-J/Mitf-J, which we show is expressed in
      multiple cell types. The MITF/Mitf locus is over 200 kb in length, with strong
      but imperfect exon conservation between human and mouse. MITF/Mitf tissue
      expression data are presented from multiple datasets, including EST expression
      patterns and isoform-specific RT-PCR. The majority of isoforms were found to be
      broadly expressed, with the M- and Mc-isoforms being tissue-restricted to
      melanocytes and mast cells, respectively. Consequently, a detailed
      characterization of this complex locus may help to identify additional unknown
      deafness-pigmentary syndrome mutations in human kindred and permit a better
      understanding of tissue-regulated expression that likely underlies divergent
      biological functions of this factor across multiple cell types.

PMID- 15715980
TI  - The multifunctional family of secreted proteins containing a C-type lectin-like
      domain linked to a short N-terminal peptide.
AB  - PSP/Lithostathine/PTP/regI, PAP/p23/HIP, reg1L, regIV and "similar to PAP" are
      the members of a multifunctional family of secreted proteins containing a C-type
      lectin-like domain linked to a short N-terminal peptide. The expression of this
      group of proteins is controlled by complex mechanisms, some members being
      constitutively expressed in certain tissues while, in others, they require
      activation by several factors. These members have several apparently unrelated
      biological effects, depending on the member studied and the target cell. These
      proteins may act as mitogenic, antiapoptotic or anti-inflammatory factors, can
      regulate cellular adhesion, promote bacterial aggregation, inhibit CaCO3 crystal
      growth or increase resistance to antitumoral agents. The presence of specific
      receptors for these proteins is suggested because biological effects were
      observed after the addition of purified protein to culture media or after
      systemic administration to animals, whereas other biological effects could be
      explained by their biochemical capacity to form homo or heteromers or to form
      insoluble fibrils at physiological pH.

PMID- 15715981
TI  - Identification and characterization of a L-tyrosine decarboxylase in
      Methanocaldococcus jannaschii.
AB  - Methanofuran is the first coenzyme in the methanogenic pathway used by the
      archaeon Methanocaldococcus jannaschii, as well as other methanogens, to reduce
      CO2 to methane. The details of the pathway for the biosynthesis of methanofuran
      and the responsible genes have yet to be established. A clear structural element
      in all known methanofurans is tyramine, likely produced by the decarboxylation of
      L-tyrosine. We show here that the mfnA gene at M. jannaschii locus MJ0050 encodes
      a thermostable pyridoxal phosphate-dependent L-tyrosine decarboxylase that
      specifically produces tyramine. Homologs of this gene are widely distributed
      among euryarchaea but are not specifically related to known bacterial or plant
      tyrosine decarboxylases.

PMID- 15715982
TI  - Metabolism of 1,8-cineole by human cytochrome P450 enzymes: identification of a
      new hydroxylated metabolite.
AB  - Human metabolism of the monoterpene cyclic ether 1,8-cineole was investigated in
      vitro and in vivo. In vitro, the biotransformation of 1,8-cineole was
      investigated by human liver microsomes and by recombinant cytochrome P450 enzymes
      coexpressed with human CYP-reductase in Escherichia coli cells. Besides the
      already described metabolite 2alpha-hydroxy-1,8-cineole we found another
      metabolite produced at high rates. The structure was identified by a comparison
      of its mass spectrum and retention time with the reference compounds as 3alpha
      hydroxy-1,8-cineole. There was a clear correlation between the concentration of
      the metabolites, incubation time and enzyme content, respectively. CYP3A4/5
      antibody significantly inhibited the 2alpha- and 3alpha-hydroxylation catalyzed
      by pooled human liver microsomes. Further kinetic analysis revealed that the
      Michaelis-Menten K(m) and V(max) for oxidation of 1,8-cineole in position three
      were 19 microM and 64.5 nmol/min/nmol P450 for cytochrome P450 3A4, and 141
      microM and 10.9 nmol/min/nmol P450 for cytochrome P450 3A5, respectively. To our
      knowledge, this is the first time that 3alpha-hydroxy-1,8-cineole is described as
      a human metabolite of 1,8-cineole. We confirmed these in vitro results by the
      investigation of human urine after the oral administration of cold medication
      containing 1,8-cineole. In human urine we found by GC-MS analysis the described
      metabolites, 2alpha-hydroxy-1,8-cineole and 3alpha-hydroxy-1,8-cineole.

PMID- 15715983
TI  - Anti-trypanosomal activities of DNA topoisomerase inhibitors.
AB  - Only four drugs are available for chemotherapy of human African sleeping sickness
      with undesirable toxic side effects. The development of new anti-trypanosomal
      drugs is, therefore, urgently required. In this study, 15 DNA topoisomerase
      inhibitors, including approved anti-cancer drugs, were tested for in vitro
      activity against bloodstream forms of Trypanosoma brucei and human leukaemia HL
      60 cells. All compounds exhibited anti-trypanosomal activity, with ED50 values
      ranging between 3 nM and 30 microM, and MIC values between 100 nM and >100
      microM. The trypanocidal activities of the most effective DNA topoisomerase
      inhibitors, aclarubicin, doxorubicin and mitoxantrone, were comparable with those
      of commercial anti-trypanosomal drugs. These data support the use of DNA
      topoisomerase inhibitors as lead compounds for anti-trypanosomal drug
      development.

PMID- 15715984
TI  - HIV epidemic in Central India: trends over 18 years (1986-2003).
AB  - In this report, we present the occurrence of HIV seropositivity and trends over
      last 18 years in a heterogenous group of people attending Voluntary Counselling
      and Testing Centre (VCTC) in Central India. The first Indian HIV positive person
      was reported in 1992 at the Centre. The occurrence of HIV infection increased
      from nil in 1986 to 19.9% in 2003. The HIV seropositivity was higher in males
      (6.9%) than in females (3.3%). Highest prevalence was seen in the age group of 25
      29 years in both males and females. Heterosexual route was the commonest route of
      transmission. Relative decline was observed as regards to the blood borne
      transmission. No intravenous drug abuser was reported. The study highlights a
      need for comprehensive policies to control the HIV epidemic in Central India.

PMID- 15715985
TI  - Modeling of negative autoregulated genetic networks in single cells.
AB  - We discuss recent developments in the modeling of negative autoregulated genetic
      networks. In particular, we consider the temporal evolution of the population of
      mRNA and proteins in simple networks using rate equations. In the limit of low
      copy numbers, fluctuation effects become significant and more adequate modeling
      is then achieved using the master equation formalism. The analogy between
      regulatory gene networks and chemical reaction networks on dust grains in the
      interstellar medium is discussed. The analysis and simulation of complex reaction
      networks are also considered.

PMID- 15715986
TI  - Vitamin A supplementation during war-emergency in Guinea-Bissau 1998-1999.
AB  - BACKGROUND: Vitamin A supplementation is recommended by WHO in emergency
      situations. OBJECTIVE: To evaluate the impact of Vitamin A supplementation on
      childhood mortality in an emergency situation. DESIGN: Since this was not a
      randomised study, we evaluated the impact in different ways; we used the
      variation in the delay of provision of Vitamin A in a step-wedged design,
      compared wartime with pre-wartime mortality and examined whether Vitamin A as a
      free commodity reduced cultural and social-economic inequalities in childhood
      mortality. SUBJECTS: 5926 children 6 months to 5 years of age, resident in four
      suburbs in the capital of Guinea-Bissau between October 1, 1998 and March 31,
      1999. INTERVENTIONS: From October 1, 1998 until the end of the war in 1999 all
      children present in the study area were offered Vitamin A at regular three
      monthly visits to their homes. RESULTS: Using the variation in the provision of
      Vitamin A, we found a slight non-significant reduction in mortality for children
      between 6 months and 5 years of age (mortality ratio (MR) 0.49; 95% CI 0.09
      2.70). Comparing with a three-year period before the war, children offered
      Vitamin A at home during the war had a 12% reduction in mortality (MR 0.88; 0.41
      1.87), whereas the overall impact of the war was an 89% increase in mortality (MR
      1.89; 1.32-2.71). Vitamin A supplementation was associated with a reduction in
      cultural and socio-economic inequalities. CONCLUSIONS: Vitamin A supplementation
      may have a beneficial impact on childhood mortality in an emergency situation.

PMID- 15715988
TI  - Pneumonia in patients who require prolonged mechanical ventilation.
AB  - Nosocomial pneumonia is the most important infectious disease in patients who
      require prolonged mechanical ventilation. Understanding of the etiology helps to
      prevent ventilator-associated pneumonia (VAP). VAP can develop in four ways: by
      aspiration, inhalation, hematogenous spread and by contiguous spread. The two
      most common are aspiration from the oropharyngeal region and inhalation, usually
      from manipulation of tubing or infected equipment. VAP is prevented by hand
      washing, keeping the head of the bed at 45 and, in some cases, by treating the
      surface bacteria which usually cause VAP. Sputum can be used for the diagnosis of
      VAP in most of these patients instead of invasive bronchoscopy. However, if the
      patients are critically ill, then bronchoscopy is used. Treatment in these
      patients depends on the bacteria. Pseudomonas is treated by two drugs (beta
      lactam plus a quinolone or aminoglycoside), Acinetobacteria by
      ampicillin/sulbactam or carbapenam, extended-spectrum beta-lactam-producing
      bacteria by carbapenums, and Staphylococcus by vancomycin or linezolid.

PMID- 15715989
TI  - Diagnosis of ventilator-associated pneumonia.
AB  - The diagnosis of ventilator pneumonia remains a controversial area. Use of
      standard clinical criteria has been found to be inadequate. Use of a clinical
      pulmonary infection score (CPIS) has improved the diagnostic utility of clinical
      criteria. For the intubated patient, there is ready access to the lower
      respiratory tract. Samples include endotracheal aspirates, bronchoalveolar lavage
      and protected brush specimen. The latter two can be obtained blindly or via a
      bronchoscope. The culture results are more meaningful if reported in a semi
      quantitative model. There is increasing evidence that culture results predict
      mortality and can be used to direct duration and type of therapy.

PMID- 15715990
TI  - Higher frequency of premature stop codon mutations at vpu gene of human
      immunodeficiency virus type 1 CRF01_AE compared with those of other subtypes.
AB  - Our previous study demonstrated the anti-apoptosis function of the human
      immunodeficiency virus type 1 (HIV-1) vpu gene product in normal CD4+ T
      lymphocytes. In this study, using sequences obtained from the HIV sequence
      database, we compared vpu sequences from 184 preparations of various subtypes of
      HIV-1 from diverse geographical regions. Our analysis revealed that CRF01_AE
      isolates had premature stop codon mutations at the vpu gene at a much higher rate
      (36%) than other subtypes (0-9%). The premature stop codon mutations in vpu
      existed mostly at two amino acid residues: the methionine initiation codon and
      the boundary between the transmembrane (TM) and cytoplasmic domains. The
      mutations at the latter site were more often detected in CRF01_AE. The higher
      mutation rates at vpu in CRF01_AE were confirmed by sequence comparison of
      polymerase chain reaction products newly obtained directly from the DNA extracted
      from peripheral blood mononuclear cells (PBMCs), but not from the RNA from the
      plasma, in CRF01_AE- and subtype B-infected individuals. This finding may
      indicate the possibility that the more abundant population of HIV-1 CRF01_AE is
      able to induce apoptosis in CD4+ T lymphocytes than the populations of other
      subtypes.

PMID- 15715991
TI  - Enterotoxins and toxic shock syndrome toxin in Staphylococcus aureus recovered
      from human nasal carriers and manually handled foods: epidemiological and genetic
      findings.
AB  - A set of 269 Staphylococcus aureus isolates recovered from nasal carriers and
      manually handled foods in a region of Spain was analyzed for pyrogenic toxin
      production and toxin genes. Fifty-seven isolates producing at least one of four
      enterotoxins (SEA, SEB, SEC, SED), 10 isolates producing only toxic shock
      syndrome toxin (TSST-1), and 10 isolates producing both toxin types were found.
      The 77 toxigenic isolates were discriminated into 36 SmaI genomic and 13 EcoRI
      plasmid profiles. A strong relationship between toxin profiles with both SmaI
      genomic and EcoRI plasmid profiles was revealed. SmaI genomic profiles showing
      six or less mismatching fragments and similarity coefficient > or =0.7 were
      included in a lineage. Eight lineages were differentiated; six of them grouped
      both human and food isolates and two of these also included outbreak-implicated
      isolates. Two lineages, represented by TSST-SEA and TSST-1, on the one hand, and
      SEC and SEC-SED isolates, on the other hand, were the most frequent, but only the
      second was outbreak-related. When SmaI genomic and EcoRI plasmid profiles were
      hybridized with tst, sea, seb, and sec toxin probes, it was observed that each
      probe mapped on a different SmaI fragment from isolates falling into the same
      lineage. All of the probes only mapped on genomic fragments, but sed also mapped
      on three plasmid fragments. When sej and ser probes were included, they mapped
      together with sed on the chromosome and on the plasmids. Two plasmids (ca. 33 and
      36 kb) carried the expected sed-sej-ser genes, while the other (ca. 53.5 kb)
      carried sed-sej and ser-like genes. The latter plasmid and the chromosomal
      location of sed-sej-ser are new findings from this study.

PMID- 15715992
TI  - Binding of the bioactive component jatrorrhizine to human serum albumin.
AB  - The interaction between Jatrorrhizine with human serum albumin (HSA) were studied
      by fluorescence quenching technique, circular dichroism (CD) spectroscopy, and
      Fourier transform infrared (FT-IR) spectroscopy. Fluorescence data revealed the
      presence of a single class of binding site on HSA and its binding constants (K)
      are 7.278 x 10(4), 6.526 x 10(4), and 5.965 x 10(4) L.mol(-1) at 296, 303, and
      310 K, respectively. The CD spectra and FT-IR spectra have proved that the
      protein secondary structure changed in the presence of Jatrorrhizine in aqueous
      solution. The effect of common ions on the binding constants was also
      investigated. In addition, the thermodynamic functions standard enthalpy
      (DeltaH(0)) and standard entropy (DeltaS(0)) for the reaction were calculated to
      be -10.891 kJ.mol(-1) and 56.267 J.mol(-1) K(-1), according to the van't Hoff
      equation. These data indicated that hydrophobic and electrostatic interactions
      played a major role in the binding of Jatrorrhizine to HSA. Furthermore, the
      displacement experiments indicated that Jatrorrhizine could bind to the site I of
      HSA, which was also in agreement with the result of the molecular modeling study.

PMID- 15715993
TI  - Loss-of-function mutations identified in the Helical domain of the G protein
      alpha-subunit, G alpha2, of Dictyostelium discoideum.
AB  - The guanine nucleotide binding regulatory proteins (G proteins) play essential
      roles in a wide variety of physiological processes, such as vision, hormone
      responses, olfaction, immune response, and development. The heterotrimeric G
      proteins consist of alpha-, beta-, and gamma-subunits and act as molecular
      switches to relay information from transmembrane receptors to intracellular
      effectors. The switch mechanism is a function of the inherent GTPase activity of
      the alpha-subunit. The alpha-subunit is comprised of two domains, the GTPase
      domain and the Helical domain. The GTPase domain performs all of the known alpha
      subunit functions while little is know about the role of the Helical domain. To
      gain a better understanding of alpha-subunit function, we performed a screen for
      loss-of-function mutations, using the G alpha2-subunit of Dictyostelium. G alpha2
      is essential for the developmental life cycle of Dictyostelium. It is known that
      the loss of G alpha2 function results in a failure of cells to enter the
      developmental phase, producing a visibly abnormal phenotype. This allows the easy
      identification of amino acids essential to G alpha2 function. A library of random
      point mutations in the g alpha2 cDNA was constructed using low fidelity
      polymerase chain reaction (PCR). The library was then expressed in a g alpha2
      null cell line and screened for loss-of-function mutations. Mutations were
      identified in isolated clones by sequencing the g alpha2 insert. To date, sixteen
      single amino acids changes have been identified in G alpha2 which result in loss
      of-function. Of particular interest are seven mutations found in the Helical
      domain of the alpha-subunit. These loss-of-function mutations in the alpha
      subunit Helical domain may provide important insight into its function.

PMID- 15715994
TI  - Influence of an experimental Trypanosoma congolense infection and plane of
      nutrition on milk production and some biochemical parameters in West African
      Dwarf goats.
AB  - The interactions of trypanosomosis and plane of nutrition on health and
      productivity of multiparous and primiparous West African Dwarf (WAD) does were
      studied in a multi-factorial experiment including diet (supplementation or basal
      diet) and infection (infected or control). Experimental does were infected with
      Trypanosoma congolense at the beginning of the second week post-kidding and
      monitored for 16 weeks after infection. Trypanosome infection significantly
      reduced packed cell volume (PCV) (control: 30.1+/-0.3% versus infected: 22.2+/
      0.3%; P<0.0001). Regardless of infection, the drop in PCV from the pre-infection
      period to the end of the experiment was more severe in animals under restricted
      diet (interaction dietxperiod, P<0.001). Trypanosome parasitaemia tended to be
      higher in the supplemented group than in the basal diet group (P>0.05) and
      multiparous animals had a higher parasitaemia (score: 2.6+/-0.1) than primiparous
      animals (score: 2.2+/-0.1) (P<0.05). Trypanosome infection as well as dietary
      supplement had a significant effect on lactation length. Milk off-take from
      trypanosome-infected does was significantly lower than that from the uninfected
      control group (17.5+/-3.2l versus 35.5+/-3.2l, P<0.001) and there was a positive
      effect of plane of nutrition (supplemented: 32.8+/-3.2l and basal diet: 20.2+/
      3.5l, P=0.01). The drop in milk off-take due to trypanosome infection was more
      severe in the supplemented group (control: 46.7+/-4.7l versus infected: 18.9+/
      4.2l) than in the group receiving a basal diet (control: 24.2+/-5.0l versus
      infected: 16.1+/-4.7l) (interaction infectionxdiet, P=0.04) due to the number of
      does from the supplemented group that were withdrawn from the experiment. The
      effect of trypanosome infection on doe's live-weight was only noticeable during
      the first 8 weeks of lactation and there was no significant effect on offspring
      growth rate unless the mother died. Plasma total protein (TP), albumin and
      cholesterol concentrations were significantly reduced by the infection but were
      significantly increased by supplementation. Supplemented does had a higher level
      of cholesterol and a tendency for a higher parasitaemia. Does of high parity also
      had a higher cholesterol level than primiparous does and, based on the number of
      animals that were withdrawn from the experiment, they showed a lower resistance
      to the infection.

PMID- 15715995
TI  - Distribution of vacA and cagA genotypes of Helicobacter pylori in Kuwait.
AB  - There is considerable geographical variation in the distribution of allelic types
      of Helicobacter pylori. This first study from Kuwait determined the prevalence of
      cagA and vacA genotypes among 117 unselected patients attending a
      gastroenterology center. We found that whereas vacA s1 and s2 types were equally
      likely to be present in biopsies obtained from patients of Middle-Eastern origin,
      African Arabs were predominantly infected with s2 type and South-Asians the s1
      type. South Asians most frequently carried the cagA positive genotype with
      Bangladeshis showing the highest prevalence rate of 87%.

PMID- 15715996
TI  - Combined detection of Brugia malayi and Wuchereria bancrofti using single PCR.
AB  - A single step PCR method has been developed for the combined detection of the
      human filarial parasites, Brugia malayi and Wuchereria bancrofti. Parasites' DNA
      were isolated from filaria positive blood samples that were collected from
      endemic areas. The primers used were Hha1 and Ssp I, which amplified the DNA
      fragments of 322 bp and 188 bp specific to B. malayi and W. bancrofti,
      respectively. The sensitivity of the assay was tested with blood and mosquito
      samples having one W. bancrofti in a pool of 10 B. malayi. The assay was further
      evaluated on field collected blood and mosquito samples. Use of this assay as a
      diagnostic tool for the detection of filariasis being the most promising aspect
      of this study, offers scope for detection of both the parasites even at low
      levels of infection.

PMID- 15715997
TI  - Multimodal therapy before liver transplantation for hepatocellular carcinoma.
AB  - BACKGROUND: : The use of orthotopic liver transplantation (OLT) for the treatment
      of patients with hepatocellular carcinoma (HCC) remains controversial because of
      the risk of both exclusion from the waiting list due to tumor progression and
      post OLT HCC recurrence. The aim of the present study was to evaluate the effect
      of an aggressive HCC treatment during the waiting list time on overall and
      recurrence-free survival of HCC transplanted patients in a single institutional
      study. METHODS: : Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly
      differentiated HCC cases were excluded, while size and number of nodules were not
      considered as absolute selection criteria. In all, 90% of the study group had HCC
      treatment while on the waiting list (transarterial chemoembolization,
      percutaneous therapies, chemotherapy). RESULTS: : Only one patient (2.5%) was
      removed from the waiting list after developing neoplastic portal thrombosis 3
      months after listing, while 33 (82.5%) underwent to OLT after a median waiting
      list time of 11 months (range 3-16 months). On histological examination, 42% of
      the group did not meet the "Milan criteria" and 42% were pTNM stages III and IV.
      The median follow-up was 42 months. The 5-year actuarial survival rate was 64%
      and recurrence-free survival was 91%. HCC recurred in only two patients (6%).
      CONCLUSIONS: : The use of routine pre-OLT tumor grading and of an aggressive HCC
      treatment during the waiting list, in our experience, resulted in a very low risk
      of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence.

PMID- 15715998
TI  - Distribution of D1-like and D2-like dopamine receptors in the brain of genetic
      epileptic WAG/Rij rats.
AB  - The densities of the dopamine (DA) D1-like and D2-like receptors were studied by
      autoradiography in brain regions of rats with (WAG/Rij strain) and without (ACI
      strain) genetic absence epilepsy. The core of the nucleus accumbens in WAG/Rij
      rats had a lower density of D1-like receptors than in ACI rats, a reduction of
      both D1-like and D2-like DA receptors was also found for the dorsal striatum
      (dorsal caudate-putamen). On the other hand, the density of D2-like receptors was
      higher in cortical (frontal and parietal) regions and lower in the CA3 region of
      the hippocampus of WAG/Rij, as compared to ACI rats. These results give new
      information about possible malfunction of the brain dopaminergic system in the
      WAG/Rij rat model of absence epilepsy. It seems that there are differences
      between WAG/Rij and other models of absence epilepsy, especially concerning the
      role of striatum.

PMID- 15715999
TI  - A family of generalized epilepsy with febrile seizures plus type 2-a new missense
      mutation of SCN1A found in the pedigree of several patients with complex febrile
      seizures.
AB  - We report a family with complex febrile seizures (FS). The proband is a 15-year
      old boy with seizures that persisted beyond 6 years of age. His father, aunt, and
      cousin also have the histories of FS until 8, 9, and 8 years old, respectively. A
      base substitution 5569G-->T of voltage-gated sodium channel alpha-1 subunit gene
      was found in DNA derived from the affected members of this family.

PMID- 15716000
TI  - Distribution and abundance of microsatellites in the genome of bivalves.
AB  - Understanding how microsatellites are distributed in eukaryotic genomes is
      important to clarify the differential abundance of these repeats under an
      evolutionary scenario. We have concatenated data from 3165 DNA sequences of 326
      Bivalvia species to search for taxonomic patterns of microsatellite distribution
      in genomic regions of markedly different functionality. Some microsatellite
      motifs in bivalves showed one of the lowest genomic densities observed among
      eukaryotes. Contrary to the expectation of a random distribution of
      microsatellites, they were overrepresented in introns (245 loci/Mb) compared to
      their frequency in exons (85 loci/Mb). Closely related species showed remarkable
      differences in microsatellite density suggesting species-specific properties as
      for mutation/repair efficiency on replication slippage. There was no evidence of
      a positive correlation between the density of microsatellites in intergenic DNA
      and the DNA-content. This research is relevant to better understand the forces
      shaping the distribution of microsatellites in the genome of bivalves.

PMID- 15716001
TI  - Mitochondrial genome of Pogona vitticepes (Reptilia; Agamidae): control region
      duplication and the origin of Australasian agamids.
AB  - The complete mitochondrial DNA sequence for an Australian agamid Pogona
      vitticepes was determined. Twenty-two tRNA genes, two rRNA genes, thirteen
      protein-coding genes, and two control regions were identified in this
      mitochondrial genome. The second control region was inserted between NADH
      dehydrogenase subunits 5 and 6 genes. The duplication of the control region was
      found in all Australasian agamids examined and was not found in other Asian or
      African taxa. The two control regions had nearly identical sequences within
      species but they were divergent among species, suggesting their concerted
      sequence evolution. Phylogenetic analyses including divergence time estimation
      without assuming the molecular clock suggested that the duplication of the
      control region occurred on a lineage leading to the Australasian agamids 25-45
      million years ago after their divergence from a Southeast Asian Physignathus
      cocincinus. Our finding thus supports the recent dispersal origin of Australasian
      agamids in connection with plate tectonic movement of Australia to the proximity
      of Southeast Asia.

PMID- 15716002
TI  - P450 and P450 reductase cDNAs from the moth Mamestra brassicae: cloning and
      expression patterns in male antennae.
AB  - The involvement of cytochrome P450 (CYP) enzymes in olfaction has been
      demonstrated in vertebrates over the past decade. In insects, these enzymes are
      well known for their role in biosynthesis of endogenous compounds as well as
      xenobiotic metabolism, but the presence of olfactory cytochrome P450s was poorly
      investigated. Using a PCR-based strategy, we have isolated cDNAs of two new
      microsomal P450s from the antennae of the cabbage armyworm Mamestra brassicae,
      CYP9A13 and CYP4G20 of two new microsomal P450s, as well as their red-ox partner,
      the cytochrome P450 reductase (CPR). Their distribution through the body and
      their cellular localization within the antennae were studied by RT-PCR and in
      situ hybridization. The three genes are strongly expressed in some sensory units
      of the antennae, the sensilla trichodea, which are tuned to odorants detection.
      The putative functions of the corresponding enzymes are discussed in regard to
      their respective expression patterns and to our knowledge on olfactory P450
      metabolism in mammals.

PMID- 15716004
TI  - Human ribosomal protein S26 suppresses the splicing of its pre-mRNA.
AB  - Human recombinant ribosomal protein S26 (rpS26) was shown to interact with its
      pre-mRNA intron I and mRNA fragment. Endogenous rpS26 in HeLa nuclear extract was
      also found to bind to the intron I, and with a lower extent to the mRNA fragment.
      The addition of recombinant rpS26 to the nuclear extract increased the binding
      largely. The in vitro splicing of an RNA that contained exon I, intron I and part
      of exon II of the rpS26 pre-mRNA yielded conventional and alternative mRNAs.
      Recombinant rpS26 was found to suppress the formation of both mRNAs. Sites of the
      pre-mRNA involved in the binding to rpS26 were detected by toe-printing.
      Nucleotides that caused a stop (pause) of the reverse transcription formed two
      clusters on the RNA secondary structure. One cluster including A69, A287 and A303
      arranged the conventional 3' site of splicing, another one including A131, A136,
      G156, A166 and A264 arranged the alternative 3' site of splicing.

PMID- 15716003
TI  - Intestinal SGLT1-mediated absorption and metabolism of benzyl beta-glucoside
      contained in Prunus mume: carrier-mediated transport increases intestinal
      availability.
AB  - The intestinal absorption of benzyl beta-glucoside (BNZ beta glc) contained in
      the fruit of Prunus mume SIEB. et ZUCC. (Rosaceae), which is traditionally used
      as a medicinal food in Japan, was studied in rat intestines. BNZ beta glc was
      absorbed from the mucosal to serosal sides. Its metabolite, benzyl alcohol (BAL),
      was also detected on both the mucosal and serosal sides. In the presence of
      phloridzin (Na(+)/glucose cotransporter (SGLT1) inhibitor) or in the absence of
      Na+ (driving force), BNZ beta glc absorption was significantly decreased.
      Transport clearance of BNZ beta glc across the brush border membrane decreased as
      its concentration increased. These results indicate that BNZ beta glc is
      transported by SGLT1. Metabolic clearance of BNZ beta glc also decreased as its
      concentration increased. The amount ratio of BNZ beta glc to BAL on the serosal
      side increased with the increase of BNZ beta glc concentration. The intestinal
      availability of BNZ beta glc was lower in the absence of Na+ than in the presence
      of Na+, indicating that the SGLT1-mediated transport of BNZ beta glc increases
      intestinal availability by decreasing the intestinal extraction ratio. This
      neutraceutical study concluded that intestinal carrier-mediated transport across
      the brush border membrane improves the intestinal availability of nutritionally,
      pharmacologically or physiologically active compounds that undergo intestinal
      metabolism (first-pass effect).

PMID- 15716006
TI  - Deconstructing PTI-1: PTI-1 is a truncated, but not mutated, form of translation
      elongatin factor 1A1, eEF1A1.
AB  - The prostate tumor-inducing gene 1 (PTI-1) transcript is detected in various
      human carcinoma cells. PTI-1 is reported to consist of a 5' untranslated region
      (5' UTR) homologous to mycoplasma 23S rRNA and a coding region corresponding to a
      truncated and mutated form of the translation elongation factor 1A, eEF1A. We
      have found that the PTI-1 transcript may encode a truncated, but not mutated,
      form of the human isoform eEF1A1. Additionally, the 5' UTR sequence of PTI-1 from
      genomic DNA of different cell lines and blood samples varies from the original
      sequence. This 5' -UTR region of PTI-1 presents a fusion of E. coli and
      Mycoplasma hyorhinis 23S rRNA. We have overexpressed the potential PTI-1 protein
      in E. coli and various human cell lines. The resulting protein could be detected
      by western blotting using anti-eEF1A antibodies. However, we were unable to
      detect the PTI-1 protein in LNCaP cell extracts. The potential roles of the PTI-1
      protein in carcinogenesis and the origin of the PTI-1 gene in the human genome
      are discussed.

PMID- 15716007
TI  - A surface-mediated origin of the RNA world: biogenic activities of clay-adsorbed
      RNA molecules.
AB  - The involvement of clay surfaces in the origin of the first genetic molecules on
      Earth has long been suggested. However, the formation of these polymers was not
      sufficient by itself to initiate the evolutionary process leading to the
      appearance of life. These macromolecules had to persist in primeval habitats so
      that their biological potentiality could be expressed. In this study, we assess
      the possibility of development of the RNA world on a clay substrate by
      investigating the capacity of different RNA molecules adsorbed/bound on the clay
      minerals montmorillonite (M) and kaolinite (K) to persist in the presence of a
      degrading agent (RNase-A), to interact specifically with complementary RNA
      strands, and to transmit the information contained in their nucleotide sequences.
      The RNase-A degradation of clay-adsorbed 23S rRNA from Escherichia coli was
      significantly slower (75-80%) than that observed for free rRNA, and the complete
      digestion of nucleic acid in the presence of clay was obtained in 2 vs. 1 h. Clay
      adsorbed Poly[A] homopolymer was able to recognize the complementary Poly[U]
      homopolymer present in the surrounding water solution and to establish a specific
      interaction (association) with it, possibly leading to the formation of double
      strands. Reverse transcription and amplification (RT-PCR) amplification of free
      and clay-adsorbed 16S indicated that the presence of clay particles partially
      reduced the efficiency and processivity of reverse transcriptase but did not
      inhibit its activity, demonstrating that clay-adsorbed RNA is still available for
      enzymatic replication. These findings indicate that primordial genetic molecules
      adsorbed on clay minerals would have been protected against degrading agents
      present in the environment and would have been in the right conditions to undergo
      evolutionary processes.

PMID- 15716005
TI  - Transcriptional regulation of FKLF-2 (KLF13) gene in erythroid cells.
AB  - FKLF-2 (KLF13) was cloned from fetal globin-expressing tissues and has been shown
      to be abundantly expressed in erythroid cells. In this study we examined the
      transcriptional regulation of the KLF13 gene. A 5.5 kb 5' flanking region cloned
      from mouse erythroleukemia (MEL) cell genomic DNA showed that major cis
      regulatory activities exist in the 550 bp sequence to the unique transcription
      start site, and that the promoter is more active in K562 cells than in COS-7
      cells. The promoter was trans-activated by co-expressed GATA-1 through the
      sequence containing two CCAAT motifs, suggesting that GATA-1 is involved in the
      abundant expression of KLF13 mRNA in the erythroid tissue. Dual action, i.e.
      activating effect in COS-7 and repressive effect in K562 cell, was observed on
      its own promoter, suggesting a feedback mechanism for the transcriptional control
      of the KLF13 gene in the erythroid environment. These findings provide an insight
      on the mechanism of inducible mRNA expression of the KLF13 gene in erythroid
      cells.

PMID- 15716008
TI  - Organization and base composition of tilapia Hox genes: implications for the
      evolution of Hox clusters in fish.
AB  - Hox genes encode DNA binding proteins that specify cell fate in the anterior
      posterior axis of metazoan animal embryos. While each Hox cluster contains the
      same genes among the different mammalian species, this does not happen in ray
      finned fish, in which both the number and organization of Hox genes and even Hox
      clusters are variables. Ray-finned fish are believed to have undergone an
      additional genome duplication that led to the presence of 8 Hox clusters (four
      twin pairs) in their ancestor. Here we describe the Tilapia (Oreochromis
      niloticus) Hox genes set in terms of gene content, clusters organization and base
      composition and compare it with those of pufferfish and zebrafish. We observed
      that in all these fish, when paralogous genes are conserved in both the twin
      clusters, the gene which has a lower GC level generally: (i) belongs to the less
      gene-rich (less conserved) cluster; (ii) has a reduced field of embryonic
      expression; or (iii) is a pseudogene. The relationship between the decrease of GC
      level and the loss of conservation and function of one of the paralogous genes
      from twin clusters is discussed.

PMID- 15716009
TI  - Eighty percent of proteins are different between humans and chimpanzees.
AB  - The chimpanzee is our closest living relative. The morphological differences
      between the two species are so large that there is no problem in distinguishing
      between them. However, the nucleotide difference between the two species is
      surprisingly small. The early genome comparison by DNA hybridization techniques
      suggested a nucleotide difference of 1-2%. Recently, direct nucleotide sequencing
      confirmed this estimate. These findings generated the common belief that the
      human is extremely close to the chimpanzee at the genetic level. However, if one
      looks at proteins, which are mainly responsible for phenotypic differences, the
      picture is quite different, and about 80% of proteins are different between the
      two species. Still, the number of proteins responsible for the phenotypic
      differences may be smaller since not all genes are directly responsible for
      phenotypic characters.

PMID- 15716010
TI  - The spectrum of genomic signatures: from dinucleotides to chaos game
      representation.
AB  - In the post genomic era, access to complete genome sequence data for numerous
      diverse species has opened multiple avenues for examining and comparing primary
      DNA sequence organization of entire genomes. Previously, the concept of a genomic
      signature was introduced with the observation of species-type specific
      Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified
      as the subsequences with the greatest bias in representation in a majority of
      genomes. Herein, we demonstrate that DRAP is one particular genomic signature
      contained within a broader spectrum of signatures. Within this spectrum, an
      alternative genomic signature, Chaos Game Representation (CGR), provides a unique
      visualization of patterns in sequence organization. A genomic signature is
      associated with a particular integer order or subsequence length that represents
      a measure of the resolution or granularity in the analysis of primary DNA
      sequence organization. We quantitatively explore the organizational information
      provided by genomic signatures of different orders through different distance
      measures, including a novel Image Distance. The Image Distance and other existing
      distance measures are evaluated by comparing the phylogenetic trees they generate
      for 26 complete mitochondrial genomes from a diversity of species. The
      phylogenetic tree generated by the Image Distance is compatible with the known
      relatedness of species. Quantitative evaluation of the spectrum of genomic
      signatures may be used to ultimately gain insight into the determinants and
      biological relevance of the genome signatures.

PMID- 15716012
TI  - The genome of the Pseudomonas aeruginosa generalized transducing bacteriophage
      F116.
AB  - F116 is a temperate, pilus-specific, generalized transducing phage belonging to
      the Podoviridae virus family. Its genome is linear, ds, TR, and CP DNA with a GC
      content of 63.2%. The 65 195-bp genome contains 70 putative ORFs, only 16 of
      which showed sequence similarity to Pseudomonas genomic or phage genes. While the
      current literature suggests that F116 is a non-integrating phage that maintains
      itself as a plasmid during the lysogenic life cycle, a putative int gene was
      identified. Of the phage structural genes, only the portal protein could be
      identified by homology. Analysis of F116 structural protein by one-dimensional
      SDS-PAGE revealed approximately 15 bands. MALDI-TOF MS analysis identified the
      gene encoding the major capsid protein. This protein appears to undergo
      posttranslational cleavage giving rise to a smaller capsid protein.

PMID- 15716011
TI  - Genetic features of Mongolian ethnic groups revealed by Y-chromosomal analysis.
AB  - About 20 ethnic groups reside in Mongolia. On the basis of genetic and
      anthropological studies, it is believed that Mongolians have played a pivotal
      role in the peopling of Central and East Asia. However, the genetic relationships
      among these ethnic groups have remained obscure, as have their detailed
      relationships with adjacent populations. We analyzed 16 binary and 17 STR
      polymorphisms of human Y chromosome in 669 individuals from nine populations,
      including four indigenous ethnic groups in Mongolia (Khalkh, Uriankhai, Zakhchin,
      and Khoton). Among these four Mongolian populations, the Khalkh, Uriankhai, and
      Zakhchin populations showed relatively close genetic affinities to each other and
      to Siberian populations, while the Khoton population showed a closer relationship
      to Central Asian populations than to even the other Mongolian populations. These
      findings suggest that the major Mongolian ethnic groups have a close genetic
      affinity to populations in northern East Asia, although the genetic link between
      Mongolia and Central Asia is not negligible.

PMID- 15716013
TI  - Sex-linked recombination variation and distribution of disease-related genes.
AB  - Analysis of the distribution of recombination along human chromosomes and
      correlation with sequence features and genes have been previously performed on
      one genetic map for a given chromosome, limiting therefore their validity and
      precision. In this paper, we circumvent these issues: (1) by testing the
      correlation between recombination frequency in sex-specific versions of three
      genetic maps of chromosome 21 and their content in disease-related loci compared
      to the distribution of genes along the chromosome, and (2) by reanalysing the
      previously reported chromosome 22 results (Chelala et al., J. Biol. Syst. 10
      (2002) 303-317) with updated version of the sequence and mapping tools.
      Recombination hot zones were detected and analysed on each genetic map. Despite
      local differences, for chromosome 21, recombination hot zones were found
      relatively enriched in disease-related genes on the male genetic maps. This
      contrasts with the previously described enrichment of the chromosome 22 female
      genetic map hot zones in disease-related loci (Chelala et al., J. Biol. Syst. 10
      (2002) 303-317), which was confirmed with the updated data and tools. Our study
      demonstrates that the use of different data sets and tools have only a local
      impact on the distribution of genetic recombination hot zones and provides
      evidence for gender-specific differences in enrichment in disease-related loci in
      relation with recombination frequency. Automation of such analyses and extension
      to the entire human genome will be required in order assess the general character
      of these observations and to advance in the understanding of genome-wide
      recombination patterns to help the process of identifying disease-causing genes.

PMID- 15716014
TI  - Transcription factor NF2d9 (LBP-1a) interacts with the positive regulatory
      element for the xenobiotic responsive element.
AB  - PREX is a positive regulatory element for xenobiotic responsive element (XRE)
      mediated gene expression that is located upstream of the XRE in the CYP2A8 gene.
      Using gel mobility shift assays, we demonstrated that NF2d9 (LBP-1a), a
      transcription factor related to CP2 (LBP-1c/LSF), bound directly to PREX and also
      interacts indirectly with XRE. Luciferase-reporter gene assays showed that the
      overexpression of NF2d9 enhanced PREX and XRE-driven CYP2A8 gene transcriptional
      induction. These findings suggest that the interaction of NF2d9 with PREX and XRE
      enhances XRE-driven CYP2A8 gene transcriptional induction.

PMID- 15716015
TI  - Cytomegalovirus aggravates intimal hyperplasia in rats by stimulating smooth
      muscle cell proliferation.
AB  - Epidemiological and animal studies suggest a role for cytomegalovirus (CMV) in
      restenosis. Previously, we demonstrated that proliferating smooth muscle cells
      (SMCs) in the injured arterial wall are particularly susceptible to CMV-induced
      effects. Therefore, we hypothesised that, depending on the time point of
      infection after vascular injury, CMV infection may affect cell proliferation
      either in the media or in the neointima, thereby aggravating the process of
      restenosis. In the present study, we focused on the individual layers of the
      arterial wall by evaluating, besides the neointima-to-media ratio, the medial and
      neointimal area and cellularity in the rat femoral artery. Vascular injury was
      photochemically induced in rat femoral arteries. Immediately or 14 days
      thereafter, rats were infected with rat CMV (RCMV) or mock infected. The presence
      of RCMV in the vascular wall was determined at 3, 5, 14 and 35 days after
      infection by quantitative real-time PCR. When rats were infected immediately
      after injury, a significant increase was seen only in the medial but not in the
      neointimal cross-sectional area. On the other hand, when rats were infected 14
      days after the initial injury, a significant increase was only seen in the
      neointimal area, thereby confirming our hypothesis that RCMV infection primary
      affects proliferating SMCs. As the mean number of SMCs per microm2 in both cell
      layers was unchanged despite an increase in cross-sectional area, this implies
      that RCMV stimulated SMC proliferation. Furthermore, these vascular effects were
      observed without the virus being abundantly present in the vascular wall,
      suggesting that inflammatory and immune-mediated responses to RCMV infection are
      more important in aggravating the response to vascular injury than the virus
      itself.

PMID- 15716017
TI  - The complete mitochondrial genome of a tree frog, Polypedates megacephalus
      (Amphibia: Anura: Rhacophoridae), and a novel gene organization in living
      amphibians.
AB  - In this study, we have determined the complete sequence of the mitochondrial
      genome of an Old World tree frog Polypedates megacephalus (Anura: Rhacophoridae)
      by using a long polymerase chain reaction (PCR) technique and shotgun strategy of
      sequencing. The entire mtDNA sequence is 16,473 nt long with a novel mitogenomic
      gene organization in amphibians. Unlike other neobatrachian frogs, the transfer
      ribonucleic acid (tRNA)-Leu(CUN) and tRNA-Thr genes exchange their positions in
      P. megacephalus and form a Thr-Leu(CUN)-Pro-Phe tRNA gene tetrad. Moreover, we
      found that the ATP8 gene was replaced by a noncoding sequence of 853 nt long and
      that the ND5 gene was absent in the new mitogenome. These peculiar features of P.
      megacephalus mtDNA were further studied among related anuran species by PCR
      amplification. The new sequence data was used to assess the phylogenetic
      relationships of the three living amphibian orders using neighbor-joining,
      maximum likelihood, and Bayesian methods. In agreement with most morphological
      studies, phylogenetic analyses of a whole mitochondrial genome data set suggest a
      close relationship between salamanders and frogs. Moreover, using a molecular
      clock-independent Bayesian approach for inferring dating information from
      molecular phylogenies, we have provided a rough timescale for living amphibian
      evolution. This timescale provides a working framework for future paleontological
      researches on amphibian evolution and improves our understanding of the
      evolutionary history of modern amphibians.

PMID- 15716018
TI  - Molecular mechanisms of hereditary persistence of alpha-fetoprotein (AFP) in two
      Japanese families A hepatocyte nuclear factor-1 site mutation leads to induction
      of the AFP gene expression in adult livers.
AB  - alpha-Fetoprotein (AFP) is produced abundantly in fetal liver but is hardly
      detectable in adults. In this study, we investigated two unrelated Japanese
      families with hereditary persistence of AFP. A g-->a substitution at nucleotide 
      119 (-119g-->a) in the hepatocyte nuclear factor (HNF)-1 binding site of the AFP
      promoter was identified in both families. The activity of the wild- or variant
      type human AFP promoter was evaluated by in vitro and in vivo transfection
      experiments. This substitution in the AFP promoter significantly stimulated its
      transcriptional activity in human hepatoma cells, regardless of their prior AFP
      production. The variant-type AFP promoter was also active in adult mouse livers
      in vivo. Additionally, overexpression of HNF-1alpha stimulated the activity of
      both the wild- and variant-type AFP promoters in hepatoma cells. HNF-1alpha
      expression also activated both AFP promoters even in nonhepatoma cells, and this
      activation was suppressed by nuclear factor (NF)-I overexpression. These results
      indicate that an HNF-1 binding site mutation leads to induction of the AFP gene
      expression in adult liver, and suggest that competition between HNF-1 and NF-I in
      this region is involved in transcriptional regulation of the AFP gene during
      hepatic development.

PMID- 15716016
TI  - Telomere and subtelomere of Trypanosoma cruzi chromosomes are enriched in
      (pseudo)genes of retrotransposon hot spot and trans-sialidase-like gene families:
      the origins of T. cruzi telomeres.
AB  - Here, we sequenced two large telomeric regions obtained from the pathogen
      protozoan Trypanosoma cruzi. These sequences, together with in silico assembled
      contigs, allowed us to establish the general features of telomeres and
      subtelomeres of this parasite. Our findings can be summarized as follows: We
      confirmed the presence of two types of telomeric ends; subtelomeric regions
      appeared to be enriched in (pseudo)genes of RHS (retrotransposon hot spot), TS
      (trans-sialidase)-like proteins, and putative surface protein DGF-1 (dispersed
      gene family-1). Sequence analysis of the ts-like genes located at the telomeres
      suggested that T. cruzi chromosomal ends could have been the site for generation
      of new gp85 variants, an important adhesin molecule involved in the invasion of
      mammalian cells by T. cruzi. Finally, a mechanism for generation of T. cruzi
      telomere by chromosome breakage and telomere healing is proposed.

PMID- 15716019
TI  - Alcohol abuse as an etiologic factor for hepatocellular carcinoma in Japan.
AB  - The etiologic role of alcoholic liver disease for hepatocellular carcinoma is
      uncertain. To assess the role of alcoholic liver disease on the development of
      carcinoma, we examined history of alcohol abuse and viral markers in the sera
      and/or resected specimens in 454 patients who underwent liver resection for
      hepatocellular carcinoma. Sera from 20 of the 454 patients were negative for
      hepatitis B, C, and D viruses. Of the 20 patients, one patient had autoimmune
      hepatitis, one had primary biliary cirrhosis, two had non-alcoholic
      steatohepatitis. Of the remaining 16 patients, 8 patients were alcohol abusers
      and 5 of the 8 patients were heavy alcohol abusers. Hepatitis G virus was not
      detected in sera form the 16 patients. Although hepatitis B x gene was detected
      in the cancerous and/or non-cancerous tissues in all three alcohol abusers but
      not heavy abusers and in 5 of 6 non-alcohol abusers whose surgical specimens were
      available, the gene was detected in only one of the five heavy alcohol abusers.
      The five heavy alcohol abusers had advanced hepatic fibrosis and active
      hepatitis. Alcoholic liver disease with advanced hepatic fibrosis and active
      hepatitis is a possible cause for the development of hepatocellular carcinoma.

PMID- 15716020
TI  - GeneLook: a novel ab initio gene identification system suitable for automated
      annotation of prokaryotic sequences.
AB  - With the rapid increases in the amounts of sequence data for prokaryotic genomes,
      it has become important to develop systems for automated and accurate genome
      annotation. We present herein a novel ab initio gene identification system,
      GeneLook, that predicts protein-coding open reading frames (ORFs) with high
      sensitivity and specificity with no prior knowledge of the sequence composition.
      The system predicts protein-coding ORFs in two stages, seed ORF selection and
      main prediction. In the selection of reliable seed ORFs containing at least 200
      codons, GeneLook predicts translation start sites and operon structures through
      searches for ribosome-binding sites and a novel operon prediction algorithm. The
      codon and nucleotide frequencies of seed ORFs are then used to determine values
      for two new coding-potential parameters for identification of protein-coding ORFs
      of at least 34 codons and for another parameter that improves the prediction
      accuracy for GC-rich genomes. In the main prediction, GeneLook uses these
      parameters to identify the most likely genes of a given minimal length. We
      assessed the performance of GeneLook with two indices, sensitivity and
      specificity that are defined as true positives (TP)/(TP+false negatives) and
      TP/(TP+false positives), respectively. This system predicted protein-coding ORFs
      for Escherichia coli and Bacillus subtilis with sensitivities of 96.5% and 96.2%,
      respectively, and specificities of 96.9% and 96.1%, respectively. The system also
      identified 94.1% of annotated genes of the Pseudomonas aeruginosa genome, which
      is GC-rich, with high specificity (97.2%). Furthermore, GeneLook identified
      protein-coding ORFs with high accuracy from a wide variety of prokaryotic
      genomes.

PMID- 15716021
TI  - Overexpression of mouse GlcNAc-1-phosphotransferase-gamma subunit in cells
      induced an I-cell-like phenotype of mucolipidosis.
AB  - In a screen of signal peptide-containing proteins from a mouse hypothetical
      protein library, we identified the mouse UDP-GlcNAc:lysosomal enzyme N
      acetylglucosamine-1-phosphotransferase-gamma chain (GlcNAc-1-phosphotransferase
      gamma) (GenBank accession no. , HYP36 in this study). The mouse GlcNAc-1
      phosphotransferase-gamma was localized in the Golgi complex in cells and was
      expressed ubiquitously in mouse tissues, as shown by fluorescence microscope
      analysis and a semi-quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) assay, respectively. Domain analysis showed that the mouse GlcNAc-1
      phosphotransferase-gamma had a conserved mannose-6-phosphate (M-6-P)-binding
      domain. Interestingly, we found that overexpression of the mouse GlcNAc-1
      phosphotransferase-gamma in fibroblast cell line NIH-3T3 induced accumulation of
      macromolecules, formation of large cytoplasmic vacuoles and decrease of lysosomal
      enzymes in cells. This phenotype was reminiscent of inclusion cells (I-cells)
      that were reported in mucolipidosis diseases caused by abnormal sorting of
      lysosomal proteins. Transient ectopic expression of GlcNAc-1-phosphotransferase
      gamma in endoplasmic reticulum (ER) induced lowered lysosomal enzyme activity in
      cells. These results suggested on one hand that GlcNAc-1-phosphotransferase-gamma
      is an essential subunit of the GlcNAc-1-phosphotransferase, and on the other
      hand, the molecule might not only recognize the substrates of GlcNAc-1
      phosphotransferase, but also the lysosomal proteins with M-6-P residuals.

PMID- 15716022
TI  - Expression of the gtfI gene from Streptococcus sobrinus in Streptococcus
      anginosus using integration-mediated transformation system.
AB  - We have constructed a Streptococcus anginosus transformant expressing the gtfI
      gene from Streptococcus sobrinus, using a previously developed integration
      mediated transformation system to introduce foreign genes onto the oral
      streptococcal chromosome, and attempted to evaluate the gene expression. In this
      system, one cloning plasmid and three pACYC184 derivatives, anchor, heterodimer,
      and integration plasmids were used for the construction of a series of integrants
      via homologous recombination. A portion of S. sobrinus gtfI gene devoid of
      approximately 1 kb of the 5'-region derived from pMD39 was cloned into the
      integration plasmid and introduced onto the S. anginosus chromosome. Next, the
      polymerase chain reaction product corresponding to 2.0 kb of the 5'-region of the
      gtfI gene from S. sobrinus chromosome was further cloned into the cloning
      plasmid, and the intact gtfI gene was reconstructed following integration. The
      final S. anginosus integrant successfully secreted the enzymatically active gtfI
      gene products and extracellular enzyme was characterized. This enzyme produced
      water-insoluble glucans and glucan-forming activity was stimulated by the
      addition of dextranT10. When this integrant was grown in Todd-Hewitt broth
      supplemented with sucrose, the integrant adhered to the glass surface in vitro
      and this integrant exhibited the different colony morphology on Mitis-Salivarius
      agar plates compared to S. sobrinus and S. anginosus. These observations strongly
      suggest that the construction of S. anginosus integrant expressing S. sobrinus
      gtfI gene using this transformation system may be an effective means of analysis
      of cariogenic biofilm formation.

PMID- 15716023
TI  - Analysis of collagen fibril diameter distribution in connective tissues using
      small-angle X-ray scattering.
AB  - Analysis of the diameters of collagen fibrils provides insight into the structure
      and physical processes occurring in the tissue. This paper describes a method for
      analyzing the frequency distribution of the diameters of collagen fibrils from
      small-angle X-ray scattering (SAXS) patterns. Frequency values of fibril
      diameters were input into a mathematical model of the form factor to calculate
      the equatorial intensity which best fits the experimentally derived data from
      SAXS patterns. A minimization algorithm utilizing simulated annealing (SA) was
      used in the fitting procedure. The SA algorithm allowed for random sampling of
      the frequency values, and was run iteratively to build up an optimized frequency
      distribution of fibril diameters. Results were obtained for collagen samples from
      sheep spine ligaments. The mean fibril diameter value obtained from this data
      fitting method was 73 nm+/-20 nm (S.D.). From scanning transmission electron
      microscopy, the mean diameter was found to be 69 nm+/-14 nm (S.D.). The good
      agreement between the two methods demonstrates the reliability of the SAXS method
      for the tissue examined. The non-destructive nature of this technique, as well as
      its statistical robusticity and capacity for large sampling, means that this
      method is both quick and effective.

PMID- 15716024
TI  - Cytochrome P450 expression and catalytic activity in coronary arteries and liver
      of cattle.
AB  - There is increasing evidence that cytochrome P450 (CYP) enzymes are involved not
      only in the metabolism of xenobiotics, but also in vascular homeostasis. Among
      the CYP-derived vasoactive agents, special importance is assigned to endogenous
      products from arachidonic acid (AA). Specifically, the vasodilator
      epoxyeicosatrienoic acids (EETs), being linked to the CYP 2B, 2C, and 2J
      subfamilies, and the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE)
      connected instead to the CYP 4A subfamily and, to a lesser degree, to isoforms of
      the CYP 1A and 2E subfamilies. Here, we have examined the occurrence of
      functional CYP isoforms in the coronary arteries of cattle by RT-PCR with
      sequence verification, Western immunoblotting, and analysis of distinct catalytic
      activities with fluorescent substrate probes. Liver tissue was examined
      comparatively. Coronary tissue expressed mRNA transcripts and immunoreactive
      proteins belonging to the CYP 1A, 2C, 2E, and 2J subfamilies. Appropriate
      catalytic activity was ascertained with all these CYP species except 2J. A
      broader spectrum of CYP enzymes (CYP 1A, 2B, 2C, 2D, 2E, 2J, 3A, 4A subfamilies)
      was found in liver tissue with catalytic activities exceeding many fold those of
      coronary tissue. We conclude that bovine coronary arteries are endowed with a
      full-fledged CYP system with potential for AA-linked vasoregulation through
      dilator rather than constrictor agents. The same tissue and, to a much larger
      degree, liver tissue possess the capability of metabolizing xenobiotics via the
      CYP pathway.

PMID- 15716026
TI  - Transcription arrest caused by long nascent RNA chains.
AB  - The transcription process is highly processive. However, specific sequence
      elements encoded in the nascent RNA may signal transcription pausing and/or
      termination. We find that under certain conditions nascent RNA chains can have a
      strong and apparently sequence-independent inhibitory effect on transcription.
      Using phage T3 RNA polymerase (T3 RNAP) and covalently closed circular (cccDNA)
      DNA templates that did not contain any strong termination signal, transcription
      was severely inhibited after a short period of time. Less than approximately 10%
      residual transcriptional activity remained after 10 min of incubation. The
      addition of RNase A almost fully restored transcription in a dose dependent
      manner. Throughout RNase A rescue, an elongation rate of approximately 170 nt/s
      was maintained and this velocity was independent of RNA transcript length, at
      least up to 6 kb. Instead, RNase A rescue increased the number of active
      elongation complexes. Thus transcription behaved as an all-or-none process. The
      mechanism of transcription inhibition was explored using electron microscopy and
      further biochemical experiments. The data suggest that multiple mechanisms may
      contribute to the observed effects. Part of the inhibition can be ascribed to the
      formation of R-loops between the nascent RNA and the DNA template, which provides
      "roadblocks" to trailing T3 RNAPs. Based on available literature we discuss
      possible in vivo implications of the results.

PMID- 15716025
TI  - Examination of the distribution of the transferrin homologue, melanotransferrin
      (tumour antigen p97), in mouse and human.
AB  - Melanotransferrin (MTf) is a transferrin homologue initially identified in
      melanoma cells. Serum transferrin (Tf) contains two iron (Fe)-binding sites and
      plays a vital role in Fe transport. However, human MTf has only a single, high
      affinity, Fe-binding site. Furthermore, while isolated MTf can bind Fe, it plays
      little role in Fe uptake by cells and its function remains elusive. To further
      understand the biological role of this molecule, we examined the expression
      profile of mouse MTf (mMTf) and human MTf (hMTf) and the splice variant of the
      latter. Analysis of mMTf in 18 normal mouse tissues and 4 embryonic stages (7-17
      days) using an RNA dot blot demonstrated it was expressed at high levels in the
      pancreas, salivary gland and epididymis of the adult, while embryonic tissues
      showed low expression. The expression pattern was very different from that of
      mouse transferrin receptor 1 (TfR1) mRNA, which was found at high levels in the
      spleen and embryo. Using the more sensitive RT-PCR technique, mMTf expression was
      demonstrated across all 24 normal mouse tissues assessed. Analysis of the mMTf
      genomic sequence predicted only one mMTf transcript, although two putative
      transcripts were found in the testis using Northern blotting. An alternate hMTf
      transcript, h delta MTf, has been identified by others, although its tissue
      distribution was not previously examined. In human heart and skeletal muscle,
      three putative hMTf transcripts were identified at approximately 2, 3 and 4 kb,
      the smallest transcript being consistent with h delta MTf. The two larger
      transcripts were also found in 10 other human tissues. The h delta MTf transcript
      was detected using RT-PCR and Southern blotting in tumour-derived cell lines,
      with the highest expression being identified in melanoma cells.
      Immunohistochemistry showed that hMTf was expressed primarily within epithelia.
      In fact, the most pronounced expression was within the epidermis of the skin,
      tubules of the kidney and the ducts of sweat and salivary glands. The
      distribution of MTf and its splice variants may provide clues to their possible
      biological roles.

PMID- 15716027
TI  - Degenerative neuronal changes in the rat thalamus induced by status epilepticus
      at different developmental stages.
AB  - SE was induced in Wistar rats at post-natal (P) days 12, 15, 18, 21, and 25 to
      determine distribution and severity of thalamic damage in relation to time after
      SE. Six different intervals from 4 h up to 1 week were studied using Fluoro-Jade
      B (FJB) staining. Severity of damage was semi-quantified for every age-and
      interval group. Distribution of neuronal damage within various thalamic nuclei
      was mapped by a computer-aided digitizing system. A consistent neuronal damage
      occurred in functionally heterogenous thalamic nuclei. Damage was found in all
      age groups although its extension and time course as well as the number of
      involved thalamic nuclei varied. Number of injured thalamic nuclei rapidly
      increased with age on SE-onset. In P12 group, degenerating neurons were
      consistently seen in the mediodorsal and lateral dorsal thalamic nuclei. Since
      P15, neurodegeneration was observed additionally in midline, ventral and caudal
      thalamic nuclei (visual and auditory thalamic nuclei), in the lateral posterior
      and in the reticular nucleus. In P21 and P25 animals, the majority of thalamic
      nuclei exhibited marked neuronal damage. Nuclei with a small number (anterior and
      intralaminar) or no FJB-positive neurons (the ventral nucleus of the lateral
      geniculate body) were exceptional. The pattern of thalamic damage is age
      specific; its extent and severity increases with age.

PMID- 15716028
TI  - Variable selection pressures across lineages in Trichodesmium and related
      cyanobacteria based on the heterocyst differentiation protein gene hetR.
AB  - Due to the irreversible inhibition of nitrogenase by O2, N2 fixation is
      incompatible with the oxygenic photosynthesis of cyanobacteria. These organisms
      have therefore evolved various strategies for growing diazotrophically. One group
      of N2-fixing cyanobacteria has specialized cells, heterocysts, which contain the
      nitrogenase, lack the oxygenic photosystem II, and are virtually anoxic inside as
      the result of respiratory activity and a thick glycolipid cell wall. The hetR
      gene encodes a serine protease which is thought to be involved in the regulation
      of heterocyst development and in DNA binding. Although hetR is also present in
      many non-heterocystous N2-fixing cyanobacteria, its function in these organisms
      is unknown. In this study, hetR sequences of the N2-fixing, non-heterocystous
      cyanobacterium Trichodesmium spp. and related genera were examined for signatures
      of selection. In parsimony- or distance-based hetR phylogenies, the filamentous
      non-heterocystous cyanobacteria Symploca sp. and Leptolyngbya sp. were closest to
      Trichodesmium sp. However, accommodating molecular attributes of hetR such as
      nucleotide frequencies and rate heterogeneity in phylogenetic analyses suggested
      that many other genera could not be excluded as sister taxa of Trichodesmium.
      Maximum likelihood analysis of the dN/dS ratio (omega) showed that-irrespective
      of the use of Symploca, Leptolyngbya, or more distant taxa as an outgroup-the
      lineage between an outgroup and Trichodesmium (omega1=0.02-0.05) and a lineage
      leading to Trichodesmium erythraeum (omega1=0.02) were under much stronger
      purifying selection than the other lineages in Trichodesmium (omega0=0.13-0.32).
      Although the results from the maximum likelihood analyses are most trustworthy
      because of codon usage bias in Trichodesmium, the results from a simpler tree
      based McDonald-Kreitman test were in general agreement. Due to their quite
      different assumptions, the combination of these two methods of analysis
      circumvents multiple testing which, in general, is problematic when using branch
      models. Although the causal selective forces underlying the substitution patterns
      in hetR have not yet been identified, these findings parallel the variety of
      physiological, molecular, and behavioral differences in cyanobacteria related to
      N2 fixation. The heterogeneity of selection pressures in Trichodesmium is more
      surprising, because multiple adaptation mechanisms have not been described in
      this genus.

PMID- 15716029
TI  - Identification, structure, and phylogenetic relationships of a mitogen-activated
      protein kinase homologue from the parasitic protist Entamoeba histolytica.
AB  - A gene encoding mitogen-activated protein kinase (MAPK) from the human enteric
      parasite, Entamoeba histolytica has been identified. Sequence analyses of the
      polymerase chain reaction (PCR) and reverse transcription PCR (RT-PCR) products
      reveal that the EhMAPK gene is intronless and encodes a protein of 352 amino
      acids. EhMAPK shows significant homology with other MAPKs and contains the 11
      subdomains including the invariant residues characteristic of serine/threonine
      protein kinases. The MAPK signature residues and motifs are also present in
      EhMAPK. The atomic model of EhMAPK built with rat ERK2 as template exhibits the
      conservation of all major secondary structural features. However, a deletion in
      close proximity to the dual phosphorylation/activation site is of particular
      interest as it may have functional implications. Phylogenetic analysis indicates
      that EhMAPK is tightly clustered with Giardia intestinalis ERK2 and Dictyostelium
      discoideum ERK2. Detailed sequence analysis and phylogenetic study aided us to
      postulate that EhMAPK belongs to the extracellular signal-regulated kinase (ERK)
      family. Although EhMAPK bears good homology and phylogenetic closeness with human
      ERK8 and rat ERK7, sequence analysis indicates that they may be functionally
      different. The significant differences such as the deletions in the vicinity of
      the phosphorylation lip, variations in the P+1 specificity pocket, presence of
      additional acidic amino acids in the common docking domain provide a ground for
      postulations that activators and substrates for EhMAPK may be to some extent
      divergent from that of the ERKs of the mammalian host. Although functional
      characterization of EhMAPK remains to be done, this is the first study of any
      member of the MAPK signaling system in this organism.

PMID- 15716030
TI  - Establishment of male-specific epigenetic information.
AB  - The setting of male-specific epigenetic information is a complex process, which
      involves a major global re-organisation, as well as localized changes of the
      nucleus structure during the pre-meiotic, meiotic and post-meiotic stages of the
      male germ cell differentiation. Although it has long been known that DNA
      methylation in targeted regions of the genome is associated with male-specific
      genomic imprinting, or that most core histones are hyperacetylated and then
      replaced by sperm-specific proteins during the post-meiotic condensation of the
      nucleus, many questions remain unanswered. How these changes interact, how they
      affect the epigenetic information and how the paternal epigenetic marks
      contribute to the future genome are indeed major issues remaining to be explored.

PMID- 15716031
TI  - The mitochondrial genome organization of the rice frog, Fejervarya limnocharis
      (Amphibia: Anura): a new gene order in the vertebrate mtDNA.
AB  - The mitochondrial DNA of the rice frog, Fejervarya limnocharis (Amphibia, Anura),
      was obtained using long-and-accurate polymerase chain reaction (LA-PCR) combining
      with subcloning method. The complete nucleotide sequence (17,717 bp) of
      mitochondrial genome was determined subsequently. This mitochondrial genome is
      characterized by four distinctive features: the translocation of ND5 gene, a
      cluster of rearranged tRNA genes (tRNAThr, tRNAPro, tRNA(Leu CUN)), a tandem
      duplication of tRNAMet gene, and eight large 89-bp tandem repeats in the control
      region, as well as three short noncoding regions containing two repeated motifs
      existing in the gene cluster of ND5/tRNAThr/tRNAPro/tRNALeu/tRNAPhe. The tandem
      duplication of gene regions followed by deletions of supernumerary genes can be
      invoked to explain the shuffling of tRNAMet and a cluster of tRNA and ND5 genes,
      as observed in this study. Both ND5 gene translocation and tandem duplication of
      tRNAMet were first observed in the vertebrate mitochondrial genomes.

PMID- 15716032
TI  - Enhanced excitability of hippocampal mossy fibers and CA3 neurons under dietary
      zinc deficiency.
AB  - On the basis of the evidence that susceptibility to kainate-induced seizures is
      enhanced by zinc deficiency and that glutamate concentrations in hippocampal
      extracellular fluid are excessively increased during seizures, excitability of
      hippocampal mossy fibers and CA3 neurons was examined using hippocampal slices,
      which were prepare from mice fed a zinc-deficient diet for 4 weeks. The spatio
      temporal dynamics of zinc and calcium was monitored using their indicators,
      membrane-impermeable ZnAF-2 and membrane-permeable fura-2 AM, respectively. When
      the molecular layer of dentate gyrus was stimulated with 100mM KCl for 1s, the
      increased percentages of extracellular zinc in the stratum lucidum and CA3
      pyramidal cell layer were higher in zinc-deficient mice than in the control mice,
      implying that glutamate release from the mossy fibers of the dentate granular
      cells is enhanced by zinc deficiency. Judging from the increased percentages,
      however, the amount of zinc released was estimated to be less in zinc-deficient
      mice. On the other hand, the basal calcium concentrations in the stratum lucidum
      and CA3 pyramidal cell layer detected with fura-2 were higher in zinc-deficient
      mice than in the control mice, indicating that hippocampal calcium homeostasis is
      affected by zinc deficiency. Furthermore, the increased percentage of
      intracellular calcium in the stratum lucidum by stimulation with high K+ was
      enhanced by the zinc deficiency. The alteration of hippocampal calcium
      homeostasis seems to enhance excitability of dentate granular cells in zinc
      deficiency, following by an enhanced excitability of postsynaptic structures in
      CA3 neurons.

PMID- 15716033
TI  - Long-term survival after epilepsy surgery compared with matched epilepsy controls
      and the general population.
AB  - This study evaluates if there was a difference in long-term survival between
      epilepsy surgery patients, individually matched controls with intractable
      epilepsy, and controls from the general population. In a cohort study, we
      compared the survival of patients operated with epilepsy surgery in Norway 1948
      1988 with: (1) a control group with prolonged medical treatment for intractable
      epilepsy individually matched for age, gender, and seizure type (n = 139), and
      (2) expected mortality for matched individuals in historical cohorts of the
      general population (n = 196). Survival was compared using Kaplan-Meier curves and
      stratified proportional hazards analysis. After on average 25 years of
      observation after surgery, there was no difference in survival between the
      epilepsy surgery group and the controls with intractable epilepsy (p = 0.18). The
      risk ratio for death after epilepsy surgery was 0.6 (95% CI 0.4-1.1; p = 0.08)
      compared with the control group. However, survival of epilepsy surgery patients
      was lower than that of a matching general population (p < 0.001), with a risk
      ratio for death of 6.2 (95% CI 3.1-12.6; p < 0.001). In this long-term study of a
      national cohort of epilepsy surgery patients, we found no beneficial effect of
      epilepsy surgery on survival compared with a control group of medically treated
      patients with intractable epilepsy. The mortality after epilepsy surgery was
      higher than expected in the general population.

PMID- 15716034
TI  - Identification of the reptilian prolactin and its receptor cDNAs in the leopard
      gecko, Eublepharis macularius.
AB  - In spite of their physiological significance, there is no available information
      about the nucleotide sequences of prolactin (PRL) and its receptor in reptilian
      species. In order to fill this gap, PRL and its receptor cDNAs were identified in
      a reptilian species, the leopard gecko Eublepharis macularius. The deduced
      leopard gecko PRL polypeptide showed high identities with the corresponding
      polypeptides of other reptiles. The leopard gecko PRL receptor (PRLR) was
      estimated to have tandem repeated regions in its extracellular domain, which had
      been originally found in avian PRLR. Molecular phylogenetic analysis suggests
      that these tandem repeated regions were generated by the duplication of the
      extracellular region in the latest common ancestor among reptiles and birds. In
      addition, tissue distributions of PRL and PRLR in the leopard gecko were examined
      by the reverse transcription-polymerase chain reaction (RT-PCR). PRLR mRNA was
      detected in all tissues examined and highly expressed in the whole brain,
      pituitary, intestine, kidney, ovary, oviduct and testis. Whereas, PRL mRNA was
      expressed in the whole brain, pituitary, ovary and testis. The co-expressions of
      PRL and its receptor in some extrapituitary organs suggest that PRL acts as an
      autocrine/paracrine factor in such organs of the leopard gecko.

PMID- 15716035
TI  - Modifications in the myogenic program induced by in vivo and in vitro aging.
AB  - In this study, we have used high density cDNA arrays to assess age-related
      changes in gene expression in the myogenic program of human satellite cells and
      to elucidate modifications in differentiation capacity that could occur
      throughout in vitro cellular aging. We have screened a collection of 2016 clones
      from a human skeletal muscle 3'-end cDNA library in order to investigate
      variations in the myogenic program of myotubes formed by the differentiation of
      myoblasts of individuals with different ages (5 days old, 52 years old and 79
      years old) and induced to differentiate at different stages of their lifespan
      (early proliferation, presenescence and senescence). Although our analysis has
      not been able to underline specific changes in the expression of genes encoding
      proteins involved in muscle structure and/or function, we have demonstrated an
      age-related induction of genes involved in stress response and a down-regulation
      of genes involved both in mitochondrial electron transport/ATP synthase and in
      glycolysis/TCA cycle. From this global approach of post-mitotic cell aging, we
      have identified 2 potential new markers of presenescence for human myotubes, both
      strongly linked to carbohydrate metabolism, which could be useful in developing
      therapeutic strategies.

PMID- 15716036
TI  - Characterization of the pufferfish Takifugu rubripes apolipoprotein multigene
      family.
AB  - We have characterized the apolipoprotein multigene family of the pufferfish
      Takifugu rubripes. The pufferfish mainly contains 28-kDa, 27-kDa, and 14-kDa
      apolipoproteins in its plasma and was designated apo-28 kDa, apo-27 kDa, and apo
      14 kDa, respectively. N-terminal amino acid sequencing revealed that pufferfish
      apo-28 kDa and apo-27 kDa have an identical amino acid sequence except an
      additional propeptide in the former; and both are homologues of apoA-I from other
      animals. The sequence of pufferfish apo-14 kDa is homologous to that of eel apo
      14 kDa previously reported, both being apparently specific to fish. In silico
      screening, using the publicly available Fugu genome database confirmed the
      pufferfish apoA-I and apo-14 kDa genes. The database further contained the genes
      encoding four types of apoA-IV, one apoC-II and two types of apoE. Thus,
      pufferfish contains nine genes encoding apolipoprotein multigene family. Two apoA
      IV and one apoE genes were tandemly arrayed and located on one scaffold. Thus two
      sets of these genes formed two gene clusters. The apoC-II and apo-14 kDa genes
      are also located on a single scaffold. apoA-I and apo-14 kDa gene transcripts
      were mainly expressed in liver and less abundantly in brain. The transcripts of
      the former gene were also observed in intestine. In contrast, the transcripts
      encoding four apoA-IVs, one apoC-II, and two apoEs were mainly expressed in
      intestine. These structural details of pufferfish apolipoproteins and tissue
      distribution of their gene transcripts provide a novel evidence for better
      understanding of evolutionary relationships of apolipoprotein multigene family.

PMID- 15716037
TI  - Surfactant-induced refolding of lysozyme.
AB  - The surfactant-lysozyme interaction was investigated by circular dichroism,
      fluorescence, UV, dynamic light scattering, surface tension, turbidity
      measurements and lysozyme activity assay. A new way of refolding of lysozyme was
      found. It was shown that the lysozyme unfolded by anionic surfactants could be
      renatured by adding cationic surfactants. That is, lysozyme formed precipitate
      with anionic surfactants, the precipitates could be dissolved by adding a
      cationic surfactant solution, and then the lysozyme was refolded to its native
      state spontaneously. Different couples of anionic surfactants and cationic
      surfactants including C10SO3/C10NE, C12SO3/C10NE, C10SO3/C12NE, C10SO3/C12NB,
      C10SO4/C10NE and C12SO4/C10NE (C(n)SO3, C(n)SO4, C(n)NE and C(n)NB represent
      sodium alkyl sulfonate/sulfate, alkyl triethyl/butyl ammonium bromide
      respectively) were investigated, all of them gave similar results. The results
      were explained in terms of the differences between the interaction of anionic
      cationic surfactants and that of surfactant-lysozyme. It was thought that the
      formation of mixed micelles of anionic-cationic surfactants is a more favorable
      process than that of lysozyme-surfactant complexes, which induces the
      dissociation of lysozyme-surfactant complexes when cationic surfactants were
      added.

PMID- 15716038
TI  - Mutational analysis of a feruloyl esterase from Aspergillus awamori involved in
      substrate discrimination and pH dependence.
AB  - We cloned the feruloyl esterase A gene from Aspergillus awamori (AwfaeA) and
      engineered it to study substrate specificity and pH dependence of catalysis.
      Based on the crystal structures of two type-A feruloyl esterases (FAE-III and
      AnFAEA) from Aspergillus niger, residues located in the flap region of AwFAEA
      (Asp71, Thr72, Asp77, and Tyr80) were replaced with corresponding amino acid
      residues (Ile, Arg, Asn, and Phe), respectively, found in the lid of lipases from
      Rhizomucor miehei (RmLIP) and Humicola lanuginose (HlLIP). Furthermore, Asp77 of
      AwFAEA, which is conserved in Aspergillus FAEs and lipases, was replaced with a
      hydrophobic residue (Ile). Kinetic analysis of the mutant enzymes showed that the
      higher catalytic efficiency of the D77I and Y80F mutants toward alpha
      naphthylbutyrate (C4) and alpha-naphthylcaprylate (C8), respectively, was due to
      a lower K(m) value. The higher catalytic efficiency of D77N toward C4 substrate
      was due to a combination of decreased K(m) and considerably increased k(cat). The
      D71I and Y80F mutants showed some activity toward long-acyl chain esters. On the
      other hand, the D77I mutant had no detectable activity toward phenolic acid
      methyl esters and feruloylated arabinoxylan. Moreover, the pH optima of the D77I,
      D77N, and Y80F mutants increased from 5.0 to 7.0-8.0, 7.0, and 6.0, respectively.

PMID- 15716039
TI  - Connections between integrins and Rac GTPase pathways control gonad formation and
      function in C. elegans.
AB  - The integrins are a family of alphabeta heterodimeric transmembrane receptors
      that link extracellular matrix (ECM) proteins to the cytoskeleton and orchestrate
      cell behaviors. It's been suggested that integrins interact with Rho family small
      GTPases, such as Rho and Rac. We took advantage of a C. elegans nematode line
      expressing HA-betatail, a beta integrin transgene inhibiting the functions of
      endogenous integrins, to determine the combined effects of reducing PAT-3 beta
      integrin and Rac pathway activities. Double mutants of HA-betatail and unc-73, a
      guanine nucleotide exchange factor GEF for MIG-2/Rac, had body wall and vulval
      muscle abnormalities. On the other hand, HA-betatail combined with mutant CED-5,
      another Rac interacting protein, showed ovulation defects and sterility. RNA
      mediated interference (RNAi) of pat-3 on Rac mutant backgrounds also affected
      gonad structure and function. These results show a functional link between
      integrins and Rac signaling in muscles and gonads. Furthermore, data showing
      distinct phenotypes of HA-betatail with unc-73 versus ced-5 suggest some tissue
      specificity in the usage of Rac signaling pathways.

PMID- 15716040
TI  - Aging of human glyceraldehyde-3-phosphate dehydrogenase is dependent on its
      subcellular localization.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), long considered a traditional
      glycolytic protein, displays multiple activities independent of its role in
      energy generation. This functional diversity is dependent on its membrane,
      cytoplasmic or nuclear localization. GAPDH is encoded by one active gene and is
      synthesized as a single 37 kDa protein without alternate splicing. Accordingly,
      the identical protein would be present in each subcellular fraction. The
      accumulation of post-translational errors in protein structure as a function of
      oxidative stress is thought to provide a basic molecular mechanism for the aging
      process. Thus, during aging, the GAPDH protein should contain the identical
      degree of oxidative sequence alteration irrespective of its distribution. This
      would result in equivalent effects on GAPDH activity. However, conformational
      differences in GAPDH structure due to its subcellular protein, nucleic acid or
      membrane interactions could affect its degree of modification thereby selectively
      affecting its function. For that reason, we examined the subcellular expression
      and intracellular activity of GAPDH as a function of human aging. Subcellular
      GAPDH expression was quantitated by immunoblot analysis in fetal and senior human
      cells (postnuclear, nuclear, perinuclear). GAPDH activity was determined by in
      vitro assay. We now report that the aging of human GAPDH was subcellular
      dependent. Reductions of nuclear and postnuclear GAPDH activity in senior cells
      were twofold lower than that observed for the perinuclear protein. In contrast,
      the subcellular expression of the GAPDH protein was age-independent. These
      results suggest the possibility that subcellular interactions may mitigate
      oxidative stress-induced GAPDH modification in human aging. Such selective
      effects on GAPDH could affect its functional diversity.

PMID- 15716042
TI  - Molecular characterization of new members of the Hevea brasiliensis hevein
      multigene family and analysis of their promoter region in rice.
AB  - The cloning of hevein genes from Hevea brasiliensis was undertaken with the
      objective to isolate useful promoters to drive transgene expression in
      genetically engineered rubber tree. Four different full length genes were cloned
      by library screening and a fifth, a partial gene, by adaptor-anchored PCR.
      Sequence alignment revealed that hevein genes, although highly conserved in their
      transcribed region, diverged in two groups, with major differences in their
      promoter region, suggesting a more rapid evolution of the upstream regulatory
      functions of the genes than the downstream functions of their protein products.
      The promoter regions from two hevein genes representative of each group were
      isolated and analyzed in rice. Although both were functional, only the longest
      promoter sequence (PHev2.1) conferred a high level of expression to the transgene
      in various tissues of this heterologous host. It was in addition up-regulated by
      mechanical wounding and fungal infection in leaves. A number of potential cis
      regulatory elements were identified in silico and are discussed in view of the
      expression profiles observed in rice.

PMID- 15716041
TI  - Enzymatic description of the anhydrofructose pathway of glycogen degradation II.
      Gene identification and characterization of the reactions catalyzed by aldos-2
      ulose dehydratase that converts 1,5-anhydro-D-fructose to microthecin with
      ascopyrone M as the intermediate.
AB  - The anhydrofructose pathway describes the degradation of glycogen and starch to
      metabolites via 1,5-anhydro-D-fructose (1,5AnFru). Enzymes that form 1,5AnFru,
      ascopyrone P (APP), and ascopyrone M (APM) have been reported from our laboratory
      earlier. In the present study, APM formed from 1,5AnFru was found to be the
      intermediate to the antimicrobial microthecin. The microthecin forming enzyme
      from the fungus Phanerochaete chrysosporium proved to be aldos-2-ulose
      dehydratase (AUDH, EC 4.2.1.-), which was purified and characterized for its
      enzymatic and catalytic properties. The purified AUDH showing a molecular mass of
      97.4 kDa on SDS-PAGE was partially sequenced. Total 332 amino acid residues in
      length were obtained, representing some 37% of the AUDH protein. The obtained
      amino acid sequences showed no homology to known proteins but to an unannotated
      DNA sequence in Scaffold 62 of the published genome of the fungus. The alignment
      revealed three introns of the identified AUDH gene (Audh; ph.chr), thus the first
      gene coding for a neutral sugar dehydratase is identified. AUDH was found to be a
      bi-functional enzyme, being able to dehydrate 1,5AnFru to APM and further
      isomerizing the APM formed to microthecin. The optimal pH for the formation of
      APM and microthecin was pH 5.8 and 6.8, respectively. AUDH showed 5 fold higher
      activity toward 1,5AnFru than toward its analogue glucosone, when tested at
      concentrations from 0.6 mM to 0.2 M. Based on the characteristic UV absorbance of
      microthecin (230 nm) and APM (262 nm) assay methods were developed for the
      microthecin forming enzymes.

PMID- 15716043
TI  - Interleukin 10 receptor blockade--pentavalent antimony treatment in experimental
      visceral leishmaniasis.
AB  - Interleukin 10 (IL-10), a suppressive Th2 cell-type cytokine, promotes disease
      progression in experimental visceral leishmaniasis. To extend testing the
      therapeutic effects of applying IL-10 receptor (IL-10R) blockade with
      antileishmanial chemotherapy, BALB/c mice with established intracellular
      Leishmania donovani infection were injected once with anti-IL-10R mAb at the time
      low-dose, daily pentavalent antimony (Sb) therapy was initiated. In this
      treatment model, simultaneous administration of anti-IL-10R enhanced overall
      antileishmanial activity in the liver in an interferon-gamma-dependent fashion,
      and accelerated the kinetics of Sb-associated killing, induced a >10-fold Sb dose
      sparing effect and shortened the required duration of Sb treatment. These results
      suggest the possibility of using mAb-induced IL-10R blockade to develop low-dose
      and/or short-course immunochemotherapeutic regimens in visceral leishmaniasis.

PMID- 15716044
TI  - Efficacy of albendazole-GM6001 co-therapy against Angiostrongylus cantonensis
      induced meningitis in BALB/c mice.
AB  - Angiostrongylus cantonensis causes a form of parasitic meningitis in humans.
      Albendazole kills the nematode larvae staying in the brain. However, the dead
      larvae are capable of evoking a severe inflammatory response resulting in the
      brain damage. Matrix metalloproteinase 9 (MMP-9) is associated with the
      development of meningitis and with the immune inflammatory reaction. Presently,
      we studied the combination effects of albendazole and GM6001 (a MMP-9 inhibitor)
      against angiostrongyliasis in BALB/c mice. Co-administration of drugs produced
      marked effects; to kill the infecting larvae and to block MMP-9 activity. The
      combination treatment reduced MMP-9 activity by 89.2% in cerebrospinal fluid. The
      numbers of inflammatory cells increased significantly upon establishment of
      infection, but subsided upon co-treatment. Significantly fewer larvae were
      recovered from treated mice than from untreated, infected mice. The present
      results strongly suggest that co-therapy with albendazole and GM6001 may be an
      useful approach for the treatment of human angiostrongyliasis.

PMID- 15716045
TI  - Evidence for an evolutionary force that prevents epigenetic silencing between
      tail-to-tail rice genes with a short spacer.
AB  - During the course of evolution, the genome should have toned down various types
      of genomic noise, such as those that cause the unstable expression or gene
      silencing observed in transgenic organisms. We found a rice genomic segment where
      two genes, encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPs) and
      ribosomal protein small subunit 20 (rps20), are located in a tail-to-tail
      orientation and separated by only 300 bp of spacer. It is possible that this kind
      of structure would give rise to unstable expression due to antisense RNA derived
      from the neighboring gene. We examined this possibility using Northern blot,
      reverse transcription-polymerase chain reaction (RT-PCR), and 3' RACE analyses,
      but obtained no evidence for instability or antisense RNAs of these housekeeping
      genes. Comparison of the sequences in the corresponding regions among related
      rice species revealed a lower level of genetic divergence of both the 3'
      untranslated region (3'-UTRs) than of the other noncoding regions; in particular
      both of the boundaries between the 3'-UTRs and the spacer were markedly
      conserved. The conservation of both the terminal regions is most likely the
      result of purifying selection, implying a functional role for the strict
      termination of the transcription of these genes to prevent gene-silencing-related
      events.

PMID- 15716046
TI  - Identification and characterization of gene sequences expressed in wheat
      spikelets at the heading stage.
AB  - Through differential analysis of transcripts (SDDM), 85 cDNA sequences
      specifically or preferentially expressed in wheat spikelets at heading time were
      identified and cloned; 54 of them had significant homology with genomic, cDNA and
      protein and 16 with EST sequences. Among these 54 clones, 44 matched genes with
      known functions, whereas 10 detected homology with putative genes encoding
      proteins whose functions have been deduced on the basis of bioinformatic
      comparisons. Seventeen clones corresponded to genes that had never been cloned in
      cereals, 5 were related to wheat genes with known functions, and the remaining 32
      to genes cloned in other cereals. On the basis of their presumed functions, the
      54 clones were assigned to seven groups. The first four of them contained 40
      sequences likely involved in floral organ morphogenesis and gametogenesis, and
      precisely (i) sequences involved in the morphogenesis of floral organs; (ii)
      sequences expressed in pollen and/or anther tissues; (iii) sequences encoding
      transcription factors; (iv) sequences involved in signal perception and
      transduction (kinases and LRR proteins). The expression patterns of these 40
      sequences have been studied by reverse transcriptase-polymerase chain reaction
      (RT-PCR) analysis of transcripts from different tissues and spike organs of
      wheat.

PMID- 15716048
TI  - Ornithine decarboxylase activity is inhibited by the polyamine precursor amino
      acids at the protein stability level in Caco-2 cells.
AB  - High concentrations of certain amino acids are known to affect hormonal
      secretion, immune function, electrolyte balance or metabolic functions. However,
      there is a lack of knowledge regarding the molecular mechanisms responsible for
      these effects. We showed that, as well as spermidine transport, the activity of
      ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine
      biosynthesis, is decreased in human colon adenocarcinoma cells, Caco-2, following
      a 4-h supplementation with one of the two polyamine precursor amino acids, L
      arginine or L-methionine. Dose-response assays indicated that the inhibitory
      effect of supplemental L-methionine was stronger than that of supplemental L
      arginine. However, it was transient, being even replaced by ODC induction after 8
      h, whereas the inhibitory effect of L-arginine lasted for at least 8 h. Unlike L
      cysteine, neither L-methionine nor L-arginine could inhibit ODC activity in a
      crude acellular preparation of the enzyme. The inhibition of ODC activity in
      cells exposed to L-methionine or L-arginine was due to a decreased abundance of
      ODC protein without change at the mRNA level and each of these amino acids could
      counteract ODC induction by a glycine supplement. Contrary to the latter,
      supplemental L-methionine or L-arginine induced a marked decrease in ODC half
      life, concomitantly with an increase in the activity of antizyme, an ODC
      inhibitory protein. Thus, depending on their nature, amino acids can up- or
      downregulate ODC activity at the protein stability level.

PMID- 15716049
TI  - Characterization of Haemonchus contortus calreticulin suggests its role in
      feeding and immune evasion by the parasite.
AB  - Haemonchus contortus, a gastrointestinal parasite of sheep and goat feeds on the
      blood of its host and causes bleeding at the biting site. In this report, we
      demonstrate that the Ca2+ binding protein, calreticulin (CalR), is present in
      excretory/secretory products of adult worms. The secreted CalR enhanced plasma
      coagulation time. Using recombinant fragments, this property has been mapped to C
      terminal part of the molecule which has binding sites for Ca2+ as well as
      clotting factors. Complement protein C1q bound to immobilized CalR and C1q
      dependent lysis of sensitized sheep erythrocytes was inhibited by CalR, a
      function mapped to N-domain of the protein. Factor X and a 24 kDa polypeptide
      derived from prothrombin but not prothrombin bound to immobilized CalR. The
      binding site for 24 kDa polypeptide in the CalR molecule has been localized in
      the P-domain. Our results suggest at least two functions for secreted CalR:
      first, to prevent blood clotting by binding to Ca2+ and clotting factors thus
      enabling parasite to feed on the host blood and second to modulate the host
      immune response by binding to complement C1q thereby facilitating parasite's
      survival within the host.

PMID- 15716050
TI  - Cutaneous leishmaniasis associated with extensive lymphadenopathy during an
      epidemic in Ceara State, northeast Brazil.
AB  - During an epidemic of cutaneous leishmaniais in northeast Brazil a prospective
      study was conducted in order to assess clinical, parasitological and
      immunological features of cutaneous leishmaniasis in a representative sample of
      patients. A general examination was done and demographic and anthropometric data
      as well as numbers, duration, location, size, consistency and tenderness of
      enlarged lymph nodes and lesions recorded. Hematologic and biochemical parameters
      as well as Leishmania-specific antibodies were measured in the blood. Lymph node
      aspirations were performed to detect Leishmania-specific DNA by PCR. Cellular
      immunity was assessed by a leishmanin skin test. Ninety-seven patients with
      cutaneous leishmaniasis presented with a total of 181 lesions and 127 enlarged
      regional lymph nodes. In 36% the lymph node enlargement had been observed 2 days
      to 2 months before the development of a lesion. In 59% the lesions were followed
      by lymphadenopathy by 3 days to 3 months. The skin test was positive in all
      patients tested. PCR of the lymph node aspirates was positive in 63.2%. No
      significant correlations were found between positive PCR results, antibody levels
      or number of lesions. In northeast Brazil cutaneous leishmaniasis due to
      Leishmania braziliensis is constantly accompanied by an extensive
      lymphadenopathy. This may help to identify patients when lesions are still small
      or have not even developed and lymphadenopathy is the only clinical sign.

PMID- 15716051
TI  - The Terminal acidic SANT 1 (Tacs1) gene of maize is expressed in tissues
      containing meristems and encodes an acidic SANT domain similar to some chromatin
      remodeling complex proteins.
AB  - While screening for plant homologs of telomeric-complex proteins, we isolated a
      cDNA for the Terminal acidic SANT 1 (Tacs1) gene of maize, encoding a 45-kDa
      protein with a C-terminal Myb/SANT-like domain. Gene expression and protein
      modeling data indicate that the TACS1 protein may function in chromatin
      remodeling within shoot primordia or other meristem-containing tissues.

PMID- 15716052
TI  - Identification of two candidate collecting duct cell-specific cis-acting elements
      in the Hoxb-7 promoter region.
AB  - HOX genes encode highly conserved transcription factors responsible for
      developmental patterning and postnatal tissue homeostasis. Previous studies have
      shown that a 1.4-kb segment of the Hoxb-7 proximal promoter drives renal
      expression of reporter genes specifically in the ureteric bud and collecting
      ducts. In this study using stably transfected renal tubule cell lines, we have
      identified three short cis-acting sequences within this promoter segment that
      cooperate to induce high-level expression specifically in collecting duct cells.
      In addition to an inverted CCAAT box (-71/-67) that acts as an ubiquitous
      enhancer and binds the transcription factor CBF/NF-Y, two different cis-acting
      sequences, named CDSE-1 and CDSE-2 (for Collecting Duct Specific Element 1 and
      2), allow collecting duct cell-specific promoter activation. CDSE-1 (-56/-34) is
      composed of two E-boxes separated by a 9-bp GC-rich sequence. Only the latter
      sequence enhances reporter gene expression specifically in collecting duct cells.
      CDSE-2 (-34/-13) contains sequence bears high homology with a segment of the Pax
      2 promoter. CDSE-2 also conveys cell specificity but has no enhancer activity by
      itself.

PMID- 15716053
TI  - Serological and entomological survey in a zoonotic visceral leishmaniasis focus
      of North Central Anatolia, Turkey: Corum province.
AB  - In the present study, we aimed to carry out an epidemiological and entomological
      survey on a visceral leishmaniasis (VL) focus located on the northern central
      part of Anatolia, Turkey. Five villages of Corum province, where five confirmed
      cases of human visceral leishmaniasis (HVL) (one patient/village) were reported
      between June 1998 and August 2001 were included in the study. A total of 625
      children and 131 dogs were sampled and the physical examination was carried out
      by authorized physicians and veterinarians. An indirect fluorescent antibody test
      (IFAT) was performed by standard procedures for human and dog sera, while the
      direct agglutination test (DAT) was only performed for dog sera. Sand fly
      collection was performed in three villages by CDC miniature light traps.
      Hepatosplenomegaly and hepatomegaly were detected in two and eight children,
      respectively. The seropositivity rate among children was found to be 0.16%
      (1/625) in the region. The seroprevalence of canine infection in these five
      villages ranged between 0.0% and 28.26%. In two villages, named Ahlatcik and
      Asagifindikli, no seropositive dogs were found. A total of 1218 sand flies were
      collected throughout the study. Six species of Phlebotomus were identified: P.
      transcaucasicus, P. neglectus, P. halepensis, P. tobbi, P. papatasi, and P.
      jacusieli. P. transcaucasicus was found to be the predominant species in Cevizli
      (47.44%; 343/723) and Ucoluk (79.95%; 351/439) villages, while P. tobbi was
      abundant in Kucukerikli (42.85%; 24/56).

PMID- 15716054
TI  - Isolation of bacteria with antibiotic resistance from household cockroaches
      (Periplaneta americana and Blattella germanica).
AB  - Cockroaches may harbor and disseminate microorganisms to the environment. In this
      study, Periplaneta americana and Blattella germanica were collected from 40
      households in Kaohsiung City and Kaohsiung County, Taiwan. Cockroach infestation
      was found in 50% of the studied households and 226 cockroaches (123 P. americana
      and 103 B. germanica) collected by trapping. P. americana was more often found in
      the kitchen (70.7%) whereas B. germanica in the storage room (51.5%) and kitchen
      (36.9%). There was no significant difference between the percentages of P.
      americana (99.9%) and B. germanica (98.0%) carrying bacteria. A total of 25
      species of bacteria was isolated from P. americana and only 21 from B. germanica.
      Antibiotic resistance was found in Staphylococcus aureus, Enterococcus species,
      Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Serratia
      marcescens, and Proteus species isolated from the cockroaches. These findings
      suggest a potential role of cockroaches in the transmission of pathogenic
      bacteria with antibiotic resistance in households.

PMID- 15716055
TI  - Leishmania donovani amastigote component-induced colony-stimulating factor
      production by macrophages: modulation by morphine.
AB  - The neuroimmunomodulatory effects of opiates during microbial infections are now
      well known; however, not much is known during leishmaniasis. Here, we report the
      effects of morphine on purified approximately 12-kDa component of Leishmania
      donovani amastigote antigen (LDAA-12)-induced colony-stimulating factor (CSF)
      production by mouse peritoneal macrophages (PMs) in vitro. Low concentrations (1
      x 10(-9) and 1 x 10(-11) M) of morphine significantly (P < 0.05) augmented the
      production of CSFs, whereas high concentrations (1 x 10(-3) and 1 x 10(-5) M)
      inhibited CSF production. Morphine exerted a similar concentration-dependent
      biphasic effect on the LDAA-12-induced elaboration of granulocyte (G)-macrophage
      (M)-CSF (GM-CSF) and M-CSF by PMs in their conditioned medium, as quantified by
      using enzyme-linked immunosorbent assay. Furthermore, selective agonists of mu
      (DAGO) and delta-(DPDPE) opioid receptors also, respectively, augmented and
      inhibited the production of CSFs. Pretreatment of PMs with naloxone (1 x 10(-5)
      M) significantly (P < 0.05) blocked the augmenting effect of morphine. In
      contrast, at 1 x 10(-5) M, naloxone lacked any effect on the inhibitory effect of
      morphine; however, its 100-fold higher concentration partially blocked it. This
      study, apparently for the first time, demonstrates that morphine, via surface
      opioid receptors, biphasically modulates the LDAA-12-induced CSF production by
      PMs, in vitro. These results thus show the implications of opiate abuse on the
      outcome of therapeutic interventions in areas where both visceral leishmaniasis
      and drug abuse are rampant.

PMID- 15716056
TI  - Inhibitory effects of Porphyromonas gingivalis fimbriae on interactions between
      extracellular matrix proteins and cellular integrins.
AB  - Porphyromonas gingivalis is a predominant periodontal pathogen, whose fimbriae
      are considered to be a major virulence factor, especially for bacterial adherence
      and invasion of host cells. In the present study, we investigated the influence
      of fimbriae on the interactions between alphavbeta3- and alpha5beta1-integrins
      and their ligand extracellular matrix (ECM) proteins (vitronectin and
      fibronectin), using human alphavbeta3- and alpha5beta1-integrin-overexpressing
      CHO cell lines (CHOalphavbeta3 and CHOalpha5beta1, respectively). P. gingivalis
      was found to have significantly greater binding to CHOalphavbeta3 and
      CHOalpha5beta1 than to control cells, whereas a fimbria-deficient mutant showed
      negligible binding to any of the tested cell lines. CHOalphavbeta3 and
      CHOalpha5beta1 cells attached to the polystyrene culture dishes in the presence
      of their ligand ECM proteins, while fimbriae markedly inhibited those attachments
      in a dose-dependent manner, with the highest dose of fimbriae achieving complete
      inhibition. In addition, the binding of vitronectin and fibronectin to
      CHOalphavbeta3 and CHOalpha5beta1 was inhibited by P. gingivalis cells. These
      results suggest that P. gingivalis fimbriae compete with ECM proteins for
      alphavbeta3- and alpha5beta1-integrins, and inhibit integrin/ECM protein-related
      cellular functions.

PMID- 15716058
TI  - Prospects for whole genome linkage disequilibrium mapping in thoroughbreds.
AB  - Linkage disequilibrium (LD) mapping is often used in searches for genes governing
      economically significant traits and diseases. The D' coefficient is a commonly
      used measure of the extent of LD between all possible pairs of alleles at two
      markers. This study aimed to test the utility of the D' coefficient for LD
      mapping of a trait in a thoroughbred population. Microsatellite genotype data and
      grey coat colour as a trait model in a thoroughbred population were used to
      assess the extent of LD. We demonstrated that LD mapping was a reasonable
      approach for initial genome-wide scans in a thoroughbred population. Significant
      LD was demonstrated at approximately 7 cM, implying that roughly 430
      appropriately spaced microsatellites were needed for systematic whole-genome LD
      mapping in this model. LD mapping methods using D' in a thoroughbred population
      were useful for identifying the chromosomal regions for diseases and economic
      trait loci (ETL). It was suggested that a thoroughbred population represented a
      population particularly suitable for LD mapping.

PMID- 15716057
TI  - Downbeat nystagmus as a result of lamotrigine toxicity.
AB  - BACKGROUND: Downbeat nystagmus (DBN) has been reported with phenytoin and
      carbamazepine toxicity. DBN has not been described as a result of lamotrigine
      toxicity. METHODS: Clinical records, neuroimaging and video recordings were
      obtained in two patients diagnosed with intractable epilepsy who developed
      oscillopsia and incoordination while being treated with lamotrigine. One patient
      had a videonystagmographic (VNG) study. DISCUSSION: Lamotrigine's half-life is
      extended when used with valproic acid; hence, the increased chance of
      neurotoxicity associated with DBN. In our cases, DBN and truncal ataxia occurred
      in conjunction with toxic lamotrigine serum levels. CONCLUSION: Anticonvulsant
      toxicity should be considered as a cause of DBN. Lamotrigine toxicity may be an
      unusual cause.

PMID- 15716060
TI  - Efficient formation of vesicular stomatitis virus pseudotypes bearing the native
      forms of hepatitis C virus envelope proteins detected after sonication.
AB  - Hepatitis C virus (HCV) causes chronic hepatitis, liver cirrhosis and
      hepatocellular carcinoma in addition to acute hepatitis. The HCV genome encodes
      two envelope glycoproteins, E1 and E2. To investigate the role of E1 and E2 in
      HCV infection, we used a recombinant vesicular stomatitis virus (VSV),
      VSVdeltaG*, harboring the green fluorescent protein gene instead of the VSV G
      envelope protein gene. It was complemented with the native form of E1 and E2, or
      E1 or E2 alone, to make HCV pseudotypes VSVdeltaG*(HCV), VSVdeltaG*(E1), and
      VSVdeltaG*(E2). Neither E1 nor E2 expression was detected on the cell surface, as
      reported. Unlike previous reports, infectious activities of VSVdeltaG*(HCV),
      VSVdeltaG*(E1) and VSVdeltaG*(E2) pseudotypes were detected under conditions
      where VSV was completely neutralized by anti-VSV. We could enhance the infectious
      titers 100-fold by sonication upon virus harvest. Bovine lactoferrin efficiently
      inhibited infection by VSVdeltaG*(HCV) as well as VSVdeltaG*(E2), as the
      interaction between E2 and lactoferrin has been thought to contribute to the
      inhibition of HCV infectivity. VSVdeltaG*(HCV) infected many adherent cell lines,
      including hepatic cell lines, but not most hematopoietic cell lines. Treatment of
      cells with trypsin, tunicamycin, or sulfated polysaccharides before infection
      reduced the infectivity of VSVdeltaG*(HCV) by about 90%, suggesting that a cell
      surface protein(s) with sugar chains plays an important role in HCV infection.
      The VSV pseudotypes developed here would be useful for analyzing the early stages
      of HCV infection.

PMID- 15716059
TI  - Two promoters control the mouse Nmp4/CIZ transcription factor gene.
AB  - Nmp4/CIZ proteins (nuclear matrix protein 4/cas interacting zinc finger protein)
      contribute to gene regulation in bone, blood, and testis. In osteoblasts, they
      govern the magnitude of gene response to osteotropic factors like parathyroid
      hormone (PTH). Nmp4/CIZ is recurrently involved in acute leukemia and it has been
      implicated in spermatogenesis. However, these conserved proteins, derived from a
      single gene, are expressed in numerous tissues indicative of a more generalized
      housekeeping function in addition to their tissue-specific roles. To address how
      Nmp4/CIZ expression is governed, we characterized the 5' regulatory region of the
      mouse Nmp4 gene, located on chromosome 6. Two adjacent promoters P(1) [-2521
      nucleotide (nt)/-597 nt] and P(2) (-2521 nt/+1 nt) initiate transcription of
      alternative first exons (U(1) and U(2)). Both promoters lack TATA and CCAAT boxes
      but contain initiator sites and CpG islands. Northern analysis revealed
      expression of both U(1) and U(2) in numerous adult tissues consistent with the
      constitutive and ubiquitous activity of a housekeeping gene. Sequence analysis
      identified numerous potential transcription factor-binding sites significant to
      osteogenesis, hematopoeisis, and gonadal development. The promoters are active in
      both osteoblast-like cells and in the M12 B-lymphocyte cell line. Low doses of
      PTH attenuated P(1)/P(2) activity in osteoblast-like cells. The Nmp4/CIZ
      promoters are autoregulated and deletion analysis identified regions that drive
      P(1) and P(2) basal activities as well as regions that contain positive and
      negative regulatory elements affecting transcription. The Nmp4/CIZ promoters
      comprise a genomic regulatory architecture that supports constitutive expression
      as well as cell- and tissue-specific regulation.

PMID- 15716061
TI  - Depolymerized products of chitosan as potent inhibitors of tumor-induced
      angiogenesis.
AB  - Water-soluble low-molecular weight chitosan (LMWC) and chitooligosaccharides
      (COs) were obtained from chitosan (16% N-acetylation) by depolymerization induced
      by potassium persulfate under nitrogen atmosphere for 2 h. They were
      characterized by IR, X-ray, HPLC and (13)C-NMR. Splitting of C3/C5 signals in the
      latter indicated a newer conformation, and also showed prominence of acetyl
      groups in LMWC, may be due to cleavage between two consecutive deacetylated
      residues. Molecular weight of LMWC, determined by HPSEC, showed a single peak of
      approximately 37 kDa. HPLC analysis of the solvent-extracted fraction revealed
      COs enriched with pentamer, hexamer and higher oligomers. The effect of LMWC and
      COs on the growth of Ehrlich ascites tumor (EAT) cells and tumor-induced
      neovascularization was studied. COs (50 microg) were more effective compared to
      LMWC (100 microg) and proved to be potent angioinhibitory and antitumor
      compounds, as shown by inhibition of angiogenesis and inducing apoptosis as a
      function of DNA fragmentation.

PMID- 15716062
TI  - Amylopectin biogenesis and characterization in the protozoan parasite Toxoplasma
      gondii, the intracellular development of which is restricted in the HepG2 cell
      line.
AB  - The obligate intracellular protozoan Toxoplasma gondii belongs to the phylum
      Apicomplexa, which is composed of numerous parasites causing major diseases such
      as malaria, toxoplasmosis and coccidiosis. The life cycle of T. gondii involves
      developmental processes from one stage to another with both asexual and sexual
      parasitic forms. Throughout their life cycle, some apicomplexan parasites
      accumulate a crystalline storage polysaccharide analogous to amylopectin within
      the cytoplasm. In T. gondii, both the slowly dividing encysted bradyzoites and
      the sporozoites of the sexual stage contain a high number of amylopectin granules
      (AG), while the rapidly replicating tachyzoites are devoid of amylopectin. It is
      thought that this storage polysaccharide may represent an energy reserve that
      could fuel the transition from one developmental stage to another one. At
      present, by comparison to glycogen and plant starch, little is known about the
      biosynthesis, structure and biological functions of amylopectin in T. gondii.
      Here, we describe an in vitro system allowing the production and purification of
      a large amount of amylopectin, which has been subjected to detailed biochemical
      and structural analyses. Our data indicate that T. gondii synthesizes a genuine
      amylopectin following changes in the environmental conditions and that this
      storage polysaccharide differs from glycogen and starch in terms of glucan chain
      length.

PMID- 15716063
TI  - A novel isoform of Cbl-associated protein that binds protein kinase A.
AB  - A novel isoform of Cbl-associated protein (CAP) was identified in a yeast two
      hybrid screen for A-kinase anchoring proteins expressed in the heart. CAP is a
      scaffold protein implicated in insulin signaling and cytoskeleton regulation. The
      protein kinase A binding site is encoded by a previously unidentified,
      alternatively spliced exon.

PMID- 15716064
TI  - The effect of a late evening snack in patients with liver cirrhosis.
AB  - OBJECTIVES: : As an intervention for energy malnutrition, frequent meals or a
      late evening snack (LES) has been recently recommended. On the other hand, it has
      been reported that glucose intolerance is found in approximately 70% of patients
      with liver cirrhosis. Thus, we investigated which would be better for the
      improvement of energy malnutrition and glucose intolerance, treatment with LES
      alone or LES plus divided meals. METHODS: : One group of oral supplementation
      with one pack of a branched-chain amino acid (BCAA)-enriched nutrient, Aminoleban
      EN (210kcal), at 10 p.m. LES and the other group with two packs of Aminoleban EN
      (one pack at 10 p.m. as LES and another pack during the day, i.e. at sometime
      from 10 a.m. to 3 p.m.) were examined to determine the influence of LES on the
      blood glucose level, biochemical parameters, and energy metabolism. Twenty-six
      patients participated in this study. The administration period was 7 days.
      Metabolic measurements were performed using an indirect calorimeter. RESULTS: :
      The fat oxidation rate was significantly decreased and the carbohydrate oxidation
      rate significantly increased in both groups. As a result, respiratory quotient
      (RQ) was significantly improved. In many cases, the increase of the glucose level
      after meals seemed to be reduced after LES administration for 1 week. LES could
      improve energy malnutrition, and correct amino acid imbalance. There was also a
      significant correlation between non-protein respiratory quotient (npRQ) and the
      creatinine height index. CONCLUSION: : LES alone improved the energy malnutrition
      state and glucose intolerance equivalent to LES plus divided meals. Thus, LES may
      improve glucose intolerance in patients with liver cirrhosis.

PMID- 15716065
TI  - The use of positron emission tomography in hepatology.

PMID- 15716066
TI  - Characterization of an iron-regulated alpha-enolase of Bacteroides fragilis.
AB  - This study describes the identification, cloning and molecular characterization
      of the alpha-enolase P46 of Bacteroides fragilis. The gram-negative anaerobic
      bacterium B. fragilis is a member of the commensal flora of the human intestine
      but is also frequently found in severe intra-abdominal infections. Several
      virulence factors have been described that may be involved in the development of
      these infections. Many of these virulence factors are upregulated under
      conditions of iron- or heme-starvation. We found a major protein of 46 kDa (P46)
      that is upregulated under iron-depleted conditions. This protein was identified
      as an alpha-enolase. Alpha-enolases in several gram-positive bacteria and
      eukaryotic cells are located at the cell surface and function as plasminogen
      binding proteins. Localization studies demonstrated that P46 is mainly located in
      the cytoplasm and partly associated with the inner membrane (IM). Under iron
      restricted conditions, however, P46 is localized primarily in the IM fraction.
      Plasminogen-binding to B. fragilis cells did occur but was not P46 dependent. A
      60-kDa protein was identified as a putative plasminogen-binding protein in B.
      fragilis.

PMID- 15716067
TI  - Different antibody- and cytokine-mediated responses to Plasmodium falciparum
      parasite in two sympatric ethnic tribes living in Mali.
AB  - The Fulani are known to be less susceptible to Plasmodium falciparum malaria
      infections and to have lower parasitaemia despite living under similar malaria
      transmission intensity compared with other ethnic tribes. The aim of the present
      study was to examine whether the Fulani were more polarised towards Th2 as
      reflected by higher numbers of malaria-specific IL-4- and IL-10-producing cells
      and lower numbers of IFN-gamma- and IL-12-producing cells as compared to their
      neighbour ethnic tribe, the Dogon of Mali. Total IgE and both anti-malaria IgE
      and IgG antibodies were measured by ELISA and the numbers of IL-4-, IFN-gamma-,
      IL-10- and IL-12-producing cells were enumerated using enzyme-linked ImmunoSpot
      assay (ELISPOT). Numbers of parasite clones were detected by polymerase chain
      reaction (PCR). The study was performed outside the transmission period and all
      individuals included were asymptomatic. The results revealed that the Fulani were
      less parasitised, had fewer circulating parasite clones in their blood, had
      significantly higher anti-malaria IgG and IgE antibodies and higher proportions
      of malaria-specific IL-4- and IFN-gamma-producing cells compared to the Dogon.
      The higher antigen-specific production of IL-4 among the Fulani was statistically
      significant both before and after adjustment for level of spontaneous cytokine
      production, while greater IFN-gamma production only attained statistical
      significance after adjustment for spontaneous levels. Taken together, the
      association of higher anti-malarial IgE and IgG antibodies and increased numbers
      of specific IL-4- and IFN-gamma-producing cells compared to the ethnic sympatric
      tribe, the Dogon, may assist in explaining the lower susceptibility to malaria
      observed in the Fulani.

PMID- 15716068
TI  - The antigenic and catalytically active formamidase of Paracoccidioides
      brasiliensis: protein characterization, cDNA and gene cloning, heterologous
      expression and functional analysis of the recombinant protein.
AB  - Paracoccidioides brasiliensis is a well-characterized pathogen of humans. To
      identify proteins involved in the fungus-host interaction, P. brasiliensis yeast
      proteins were separated by liquid isoelectric focusing, and fractions were
      subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      Western blot analysis. Immunoreactive bands were detected with pooled sera of
      patients with P. brasiliensis infection. A protein species with a molecular mass
      of 45 kDa was subsequently purified to homogeneity by preparative gel
      electrophoresis. The amino acid sequence of four endoproteinase Lys-C-digested
      peptides indicated that the protein was a formamidase (FMD) (E.C. 3.5.1.49) of P.
      brasiliensis. The complete cDNA and a genomic clone (Pbfmd) encoding the isolated
      FMD were isolated. An open reading frame predicted a 415-amino acid protein. The
      sequence contained each of the peptide sequences obtained from amino acid
      sequencing. The Pbfmd gene contained five exons interrupted by four introns.
      Northern and Southern blot analysis suggested that there is one copy of the gene
      in P. brasiliensis and that it is preferentially expressed in mycelium. The
      complete coding cDNA was expressed in Escherichia coli to produce a recombinant
      fusion protein with glutathione S-transferase (GST). The purified recombinant
      protein was recognized by sera of patients with proven paracoccidioidomycosis and
      not by sera of healthy individuals. The recombinant 45-kDa protein was shown to
      be catalytically active; FMD activity was detected in P. brasiliensis yeast and
      mycelium.

PMID- 15716069
TI  - Genetic and biological diversity among populations of Leishmania major from
      Central Asia, the Middle East and Africa.
AB  - Evidence is provided for genetic and biological variation among Leishmania major
      strains that correlates with their geographical origin. The host-parasite
      relationship also appears to be specific. Great gerbils, Rhombomys opimus, and
      fat sand rats, Psammomys obesus, are the main reservoir hosts in Central Asia and
      the Middle East, respectively. However, the Central Asian parasite failed to
      infect the Middle Eastern rodent host in the laboratory, and vice versa. A
      permissively primed intergenic polymorphic (PPIP)-PCR and a single-stranded
      conformation polymorphism (SSCP)-PCR exposed genetic polymorphism among 30
      strains of L. major from different geographical regions. This was verified by
      subsequent sequencing of DNA from the same strains using four genomic targets:
      (a) the NADH-dehydrogenase (NADH-DH) gene, (b) the 6-phosphogluconate
      dehydrogenase (6PGD) gene, (c) the ribosomal internal transcribed spacers, and
      (d) an anonymous DNA sequence originally amplified with random primers. All the
      genetic markers indicated that the nine Central Asian strains were a separate
      homogenous genetic group. The Middle Eastern strains formed another geographical
      group that displayed heterogeneity corresponding with their different Middle
      Eastern locations. Molecular markers and host-parasite relationships confirmed
      that Central Asian and Middle Eastern strains are genetically and biologically
      distinct sub-populations of L. major. Three African strains of L. major were
      genetically closer to the Middle Eastern strains, and a representative one did
      infect fat sand rats, but they had distinct permissively primed inter-genic
      polymorphic PCR patterns and internal transcribed spacer 2 types.

PMID- 15716070
TI  - B cell response during infection with the MAT a and MAT alpha mating types of
      Cryptococcus neoformans.
AB  - In the present study, we compared the B cell response of BALB/c and C57Bl/6 mice
      during Cryptococcus neoformans infection. This response was investigated using
      virulent serotype D forms of mating types alpha and a (MAT alpha and MAT a).
      C57Bl/6 mice showed massive (mainly cerebral) infection by both types, while
      BALB/c were resistant to infection. Some resistance of C57Bl/6 mice was induced
      by previous immunization with the capsular polysaccharide from MAT alpha. Passive
      immunization of C57Bl/6 mice with purified antibody (Ab) obtained from capsular
      polysaccharide-immunized mice also increased resistance to infection. Both mouse
      strains showed comparable low IgM response to the capsular polysaccharide from
      MAT alpha, and only C57Bl/6 mice produced IgM to the polysaccharide of MAT a.
      Comparable levels of different immunoglobulin (Ig) isotypes against capsular
      components of MAT alpha and MAT a were detected, and the response of C57Bl/6 mice
      was higher when compared to that of BALB/c mice. FACS analysis indicated an
      increase in the percentage of a high-granulosity (side-scatter) splenic
      subpopulation and in the percentage of splenic Gr-1+ cells in infected C57Bl/6
      mice. In addition, the percentage of follicular splenic B cells was decreased
      after C. neoformans infection of C57Bl/6 mice. This response was more pronounced
      when we investigated infection induced by the MAT a mating type. Taken together,
      our results indicate that capsular polysaccharide derived from MAT alpha and MAT
      a types of C. neoformans have a stimulatory effect upon B cells but that there is
      no correlation between resistance of BALB/c mice and Ab production. However, the
      increase in resistance of C57Bl/6 mice parallels the production of Abs and a
      major change in splenic cell populations.

PMID- 15716071
TI  - Virulence of Paracoccidioides brasiliensis and gp43 expression in isolates
      bearing known PbGP43 genotype.
AB  - Paracoccidioides brasiliensis is the dimorphic fungus responsible for human
      paracoccidioidomycosis (PCM). We previously observed that P. brasiliensis
      isolates bearing highly polymorphic PbGP43 of genotype A (Pb2, Pb3 and Pb4) were
      phylogenetically distant from the others. The PbGP43 gene encodes an immune
      dominant diagnostic antigen (gp43), and its polymorphism reflects broader genetic
      diversity in the species. In the present study, we observed that isolates with
      PbGP43 of genotype A showed low virulence when inoculated in B10.A mice by the
      intraperitoneal, intratracheal and intravenous routes. In vitro studies detected
      sharp and prolonged down-regulation of PbGP43 in Pb3 (and not in Pb18 or Pb339)
      as a result of heat shock at 42 degrees C and temperature shift to prompt
      mycelium to yeast transition, which was, however, not disturbed. Differences in
      transcriptional regulation are possibly a consequence of mutations in the PbGP43
      promoter region, which we here show to be more polymorphic in genotype A
      isolates. As opposed to Pb3's rapid adaptation to in vitro culture conditions
      after isolation from the lung, Pb12, the most aggressive isolate tested here,
      showed slow growth and phase transition in vitro. Interestingly, animals that
      were highly infected by Pb12 produced small amounts of anti-gp43 antibodies. That
      was apparently due to down-regulation in PbGP43 expression. We present the first
      evidence of transcriptional regulation of gp43 expression, but our results
      suggest that gene expression is also regulated at the protein and/or secretion
      levels.

PMID- 15716072
TI  - Contribution of Tamm-Horsfall protein to virulence of Pseudomonas aeruginosa in
      urinary tract infection.
AB  - Tamm-Horsfall glycoprotein (THP) is the most abundant protein which is
      synthesized by renal tubular cells and excreted in urine. Its role in urinary
      tract infection has yet not been identified. In the present study, the
      contribution of THP towards adherence of Pseudomonas aeruginosa to uroepithelial
      cells and murine peritoneal macrophages was studied. Decreased adherence of THP
      coated P. aeruginosa to UECs and phagocytes was observed in vitro. In vivo, P.
      aeruginosa showed increased renal bacterial load and tissue pathology in a mouse
      model of acute ascending pyelonephritis, when THP-coated P. aeruginosa was used
      to cause infection. This study shows that THP may not necessarily act as a host
      defense component; rather, it may help in renal colonization of P. aeruginosa in
      vivo.

PMID- 15716073
TI  - Isolation and characterization of a new simian retrovirus type D subtype from
      monkeys at the Tsukuba Primate Center, Japan.
AB  - Exogenous type D simian retroviruses (SRV/D) are prevalent in captive and feral
      populations of various macaque monkeys. Thus far, five subtypes of SRV/Ds have
      been reported, three of which (SRV-1, -2 and -3) have been molecularly
      characterized. Two SRV/D strains (N27 and T150) were isolated from seropositive
      cynomolgus macaques at the Tsukuba Primate Center (TPC) in Japan, showing
      clinical signs of SRV/D infection, including anemia and persistent unresponsive
      diarrhea. Electron microscopy demonstrated that both SRV/D isolates have a virion
      morphology typical of type D retrovirus. The SRV/D N27 and T150 isolates were
      essentially the same based on sequence analysis. From homology analysis of the
      entire gag sequence, the N27 isolate is closely related to the other known SRV/Ds
      but is distinct from the three molecularly characterized SRV/Ds. Thus, we have
      tentatively designated the N27 and T150 viruses isolated from TPC cynomolgus
      macaques as SRV/D-Tsukuba (SRV/D-T).

PMID- 15716074
TI  - CD40 signaling induces reciprocal outcomes in Leishmania-infected macrophages;
      roles of host genotype and cytokine milieu.
AB  - We investigated the influence of CD40-CD40 ligand-mediated signaling on induction
      of microbicidal activity against Leishmania major in macrophages from resistant
      (B6) and susceptible (BALB) mouse strains. CD40 engagement induced leishmanicidal
      activity in resistant macrophages, but increased parasite replication in
      susceptible macrophages. CD40 engagement induced comparable TNF-alpha production
      in macrophages from both strains. However, increased IL-10 production was
      restricted to susceptible macrophages. Increased parasite replication in
      susceptible macrophages was prevented by a neutralizing anti-IL-10 antibody. In
      the presence of IFN-gamma, CD40 engagement induced Leishmania killing by
      macrophages from both strains. Therefore, the outcome of CD40 signaling on
      effector responses against L. major depends on host genotype and the cytokine
      milieu, and a source of IFN-gamma is required for a protective response.

PMID- 15716075
TI  - Burkholderia pseudomallei strain type, based on pulsed-field gel electrophoresis,
      does not determine disease presentation in melioidosis.
AB  - Melioidosis, the infection due to Burkholderia pseudomallei, may present with a
      spectrum of severity and may affect any site in the body. Differential strain
      virulence and tropism suggested by previous studies would have implications for
      virulence and vaccine work. We explored clinical correlations using pulsed-field
      gel electrophoresis (PFGE) typing in a well-characterised clinical collection.
      Two methods of analysis were used based on band-based similarity values: first, a
      conventional cluster analysis formed by the unweighted paired group mean
      analysis, and second, an analysis of the distribution of the "within-group" and
      "between-group" Dice coefficient. Clinical isolates from 114 cases of melioidosis
      occurring in the Northern Territory, Australia were studied; 71 strain types were
      defined with a Simpson's index of 0.91. No correlation was found between strain
      type and disease severity or site of melioidosis on presentation, with no
      differences in similarity values found when comparing within and between-groups.
      In particular, isolates from patients with neurological melioidosis were not
      clustered. There was evidence of geographical localisation. This study suggests
      that the variation in strain type may not be as important as host and
      environmental factors in determining the pattern of disease.

PMID- 15716076
TI  - IFN-gamma-inducible protein 10 and pentraxin 3 plasma levels are tools for
      monitoring inflammation and disease activity in Mycobacterium tuberculosis
      infection.
AB  - IFN-gamma-inducible protein 10 (IP-10/CXCL10) is a chemokine involved in delayed
      type hypersensitivity and attraction of monocytes and activated T lymphocytes at
      inflammatory foci, whereas pentraxin 3 (PTX3) is part of the innate immune
      response. In the Republic of Guinea, 220 newly diagnosed, HIV-negative, pulmonary
      tuberculosis (TB) patients were studied together with 220 healthy household
      controls and 220 community controls. CXCL10 and PTX3 blood levels were assessed
      by ELISA at diagnosis, after 2 months and at the end of treatment. In untreated
      patients, both CXCL10 and PTX3 levels were higher (P < 0.0001) than in controls,
      although household controls had higher (P < 0.0001) CXCL10 and PTX3 levels than
      community controls, but lower (P < 0.0001) than those of patients. At the end of
      treatment, 186 cured patients showed reduction (P < 0.0001) in both CXCL10 and
      PTX3 levels. In 34 patients with treatment failure, both CXCL10 and PTX3 levels
      increased further. In five previously healthy households who developed TB during
      the follow-up and in two patients who relapsed after treatment, a remarkable
      increase in both CXCL10 and PTX3 plasma levels was observed. Active TB is
      associated with increased CXCL10 and PTX3 levels in the plasma. Although not
      specific for TB, measurement of these proteins may help the monitoring of disease
      activity and efficacy of therapy.

PMID- 15716077
TI  - Stage conversion of Toxoplasma gondii RH parasites in mice by treatment with
      atovaquone and pyrrolidine dithiocarbamate.
AB  - The mouse-virulent RH strain of Toxoplasma gondii is generally considered to have
      lost its cyst-forming capacity, and conversion of RH tachyzoites into cysts in
      non-immune mice has previously been shown exclusively following early treatment
      with sulfadiazine (SDZ). We here describe the development of tissue cysts in mice
      infected with RH strain parasites and treated with atovaquone (ATO) combined with
      pyrrolidine dithiocarbamate (PDTC). Groups of Swiss-Webster mice infected
      intraperitoneally (i.p.) with 10(2) RH tachyzoites were treated with 5, 25 and
      100 mg of ATO/kg per day alone or combined with PDTC at 250 mg/kg per day from
      day 1 postinfection (p.i.) for 14 days. A total of 19 mice survived the 6-week
      observation period. Of these, brain cysts were recovered in nine (47%), with
      burdens ranging from 50 to 3120 (mean +/- S.D. = 622 +/- 963). All cyst-harboring
      mice had high specific IgG antibody levels (1:10,240-1:40,960, corresponding to
      500-2000 IU/ml), as did one mouse in which cysts were not demonstrated, which was
      therefore included in the group of mice with residual infection. Bioassay
      performed to test the infectivity of these cysts produced acute lethal
      toxoplasmosis following i.p. inoculation in all instances (100%), and
      importantly, following peroral inoculation in four (29%). The recovered
      tachyzoites were highly infectious. In addition, significantly elevated
      interferon gamma (IFN-gamma) in the treated mice which developed residual
      infection compared with any group of infection-free (treated or subinoculated)
      mice, indicates immunological control of the parasite in the latent form. In
      conclusion, early treatment of mice infected with T. gondii RH tachyzoites with
      ATO and PDTC induces conversion into tissue cysts, thus providing a new model for
      studying the mechanism(s) of T. gondii stage conversion.

PMID- 15716078
TI  - Involvement of bovine leukemia virus in induction and inhibition of apoptosis.
AB  - In a previous study, we identified an interesting mutant form of the Tax protein
      of bovine leukemia virus (BLV), designated D247G, that has an enhanced capacity
      to transactivate the long terminal repeat (LTR) of BLV and the cellular proto
      oncogene c-fos when compared with wild-type Tax (wt-Tax). We demonstrate here
      that an infectious strain of BLV containing the mutant D247G form of Tax also
      differs in its capacity to modulate cell survival both positively and negatively.
      When peripheral blood mononuclear cells (PBMCs) infected with wild-type or mutant
      BLV are cultured ex vivo with staurosporine, an agent known to induce a
      mitochondrial caspase cascade pathway regulating apoptosis, the rate of apoptosis
      is reduced to a greater extent in cells infected with mutant BLV than wild-type
      BLV, consistent with previous observations in cultures without staurosporine. The
      increase in survival was associated with an increase in expression of mRNA of bcl
      xl but not bcl-2 and bax ex vivo. In contrast, when a tissue culture-adapted cell
      line, 293T, was transiently transfected with either wild-type or mutant BLV,
      apoptosis was induced. The increase in the rate of apoptosis was higher in cells
      transfected with mutant BLV. The same difference was noted in cells transiently
      transfected with wild-type and mutant D247G Tax, suggesting that the observed
      positive and negative modulation of cell survival is attributed to the functional
      characteristics of mutant D247G Tax.

PMID- 15716079
TI  - Role of costimulatory molecules in immune response of patients with cutaneous
      leishmaniasis.
AB  - T cell-mediated immunity is critical in resistance against Leishmania parasites,
      and T cell activation requires signals provided by costimulatory molecules.
      Herein we evaluated the role of costimulatory molecules on cytokine production
      and T cell surface molecule expression by peripheral blood mononuclear cells
      (PBMC) from cutaneous leishmaniasis (CL) patients. PBMC from CL patients were
      stimulated with soluble Leishmania antigen (SLA, 10 microg/ml), in the presence
      or absence of soluble CTLA4-Ig to block CD28-B7 interaction or in the presence or
      absence of anti-human CD40L to block CD40-CD40L interaction. Supernatants were
      harvested to evaluate tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL
      10), transforming growth factor beta (TGF-beta) and interferon gamma (IFN-gamma)
      production by ELISA. Cells were harvested after 48 h of culture, stained for
      specific activation markers and analyzed by flow cytometry. Results show that the
      blockade of CD28-B7 interaction by CTLA4-Ig downmodulated IFN-gamma, IL-10, and
      TNF-alpha secretion by PBMC from CL patients. No alteration was detected on
      either TGF-beta production or the expression of CTLA44 or CD25 on CD4+ and CD8+ T
      cells. When the CD40-CD40L interaction was blockade using anti-CD40L, we did not
      observe changes in cytokine production or in surface molecule expression. The
      blockade of the CD28-B7 interactions by CTLA4-Ig also did not alter cytokine
      production in volunteers immunized against tetanus toxoid (TT). Taken together,
      these data suggest that the interaction of CTLA4 and CD28-B7 is a TGF-beta
      independent mechanism that specifically downmodulates the immune response in
      cutaneous leishmaniasis patients.

PMID- 15716080
TI  - Administration of diazepam during status epilepticus reduces development and
      severity of epilepsy in rat.
AB  - Prevention of epileptogenesis after brain insults, such as status epilepticus
      (SE), head trauma, or stroke, remains a challenge. Even if epilepsy cannot be
      prevented, it would be beneficial if the pathologic process could be modified to
      result in a less severe disease. We examined whether early discontinuation of SE
      reduces the risk of epilepsy or results in milder disease. Epileptogenesis was
      triggered with SE induced by electrical stimulation of the amygdala. Animals (n =
      72) were treated with vehicle or diazepam (DZP, 20 mg/kg) 2 h or 3 h after the
      beginning of SE. Electrode-implanted non-stimulated rats served as controls for
      histology. All animals underwent continuous long-term video
      electroencephalography monitoring 7-9 weeks and 11-15 weeks later to detect the
      occurrence and severity of spontaneous seizures. As another outcome measure, the
      severity of hippocampal damage was assessed in histologic sections. In the
      vehicle group, 94% of animals developed epilepsy. DZP treatment reduced the
      percentage of epileptic animals to 42% in the 2-h DZP group and to 71% in the 3-h
      DZP group (p < 0.001 and p < 0.05 compared to the vehicle group, respectively).
      If epilepsy developed, the seizures were less frequent in DZP-treated animals
      compared to the vehicle group (median 16.4 seizures/day), particularly in the 2-h
      DZP group (median 0.4 seizures/day). Finally, if DZP treatment was started 2 h,
      but not 3 h after SE, the severity of hippocampal cell loss was milder and the
      density of mossy-fiber sprouting was lower than in the vehicle group. These data
      indicate that treatment of SE with DZP within 2 h reduces the risk of epilepsy
      later in life, and if epilepsy develops, it is milder.

PMID- 15716081
TI  - Effects of the antiepileptic drugs lamotrigine, topiramate and gabapentin on hERG
      potassium currents.
AB  - Drugs that inhibit the cardiac rapid delayed rectifier potassium ion current
      (I(Kr)) can be proarrhythmic and their clinical use has been associated with
      sudden unexpected death (SUD) due to cardiac arrhythmia. SUD is 20-40 times more
      common among people with epilepsy than in the general population and case-control
      studies have identified polytherapy with antiepileptic drugs (AEDs) as a risk
      factor. In a previous study, it was described that the old AEDs phenytoin and
      phenobarbital had the potential to inhibit the I(Kr) channel and it was suggested
      that this could contribute to the increased risk for SUD in patients with
      epilepsy. In this study, we have investigated the I(Kr) blocking potential of
      some more recently introduced AEDs, lamotrigine (LTG), topiramate (TPM) and
      gapapentin (GBP). The whole cell patch-clamp recording technique was used to
      study the effects on I(Kr) channels expressed by the human ether-a-go-go related
      gene (hERG) stably expressed in human embryo kidney (HEK) 293 cells. Tail
      currents, which are purely related to hERG currents, were blocked with IC50 and
      IC20 (the concentrations when 50% and 20% inhibition was obtained compared to
      control values) of 229 and 21 microM, respectively, for LTG. A 40% inhibition of
      tail currents was obtained at GBP concentrations of 100 mM and a 20% inhibition
      at 54 mM. A 35% inhibition of tail currents was obtained at TPM concentrations of
      1000 microM and a 20% inhibition at 87 microM, respectively. Collective data show
      that drugs with the same margins (ratio hERG IC50/unbound therapeutic
      concentration) as LTG, may have arrhythmogenic potential. The risk for arrhythmia
      may be clinically significant in the presence of predisposing factors such as
      seizure-induced acidosis and in the case of concurrent treatment with other I(Kr)
      blocking drugs, or in case of pharmacokinetic drug-drug interactions resulting in
      excessively high concentrations of LTG.

PMID- 15716082
TI  - Anti-epileptogenic effect of beta-carotene and vitamin A in pentylenetetrazole
      kindling model of epilepsy in mice.
AB  - Vitamin A (Vit A) and its derivatives have recently been reported to be
      implicated in synaptic plasticity. In this study, the possible effect of Vit A
      and its precursor, beta-carotene on acute seizure and kindling, induced by
      pentylenetetrazole (PTZ) was assessed. Vit A and beta-carotene were evaluated for
      their ability to: (1) elevate the threshold of clonic seizures induced by i.v.
      infusion of PTZ; (2) suppress the seizures (clonic and tonic) and lethality
      induced by i.p. PTZ in PTZ-kindled mice (anticonvulsant effect); (3) attenuate
      the development of sensitization to convulsive and lethal effects of i.p. PTZ in
      kindled mice (anti-epileptogenic effect). Diazepam was employed as positive
      control. All the drugs showed anti-epileptogenic effect against PTZ-induced tonic
      seizures and lethality. Vit A and beta-carotene had no effect on clonic seizures
      threshold and also on tonic seizures and lethality induced by PTZ in kindled
      mice. Non-genomic and genomic mechanisms could be involved in the anti
      epileptogenic effect of Vit A and beta-carotene.

PMID- 15716083
TI  - Efficacy and safety of levetiracetam 1000-3000 mg/day in patients with refractory
      partial-onset seizures: a multicenter, open-label single-arm study.
AB  - PURPOSE: To evaluate the efficacy and tolerability of levetiracetam as add-on
      therapy in patients with refractory partial-onset seizures in a protocol designed
      to reflect clinical practice. METHODS: All patients in this open-label, single
      arm study entered an 8-week baseline period followed by a 4-week titration period
      and a 12-week maintenance period. Patients initially received levetiracetam 1000
      mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to
      3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the
      12-week maintenance period, the dose of levetiracetam could not be increased but
      could be decreased once if tolerability warranted. Seizure count and adverse
      events were recorded by patients in a diary. Quality of life and global
      evaluation of disease evolution were also evaluated. RESULTS: Ninety-nine
      patients were enrolled and 91 completed the study. A steady dose was maintained
      over the last 8 weeks of treatment or longer in 84 patients, with 89.3% of these
      patients receiving 3000 mg/day, 9.5% receiving 2000 mg/day, and 1.2% receiving
      1000 mg/day. A 35.9% median percent reduction from baseline in weekly frequency
      of partial-onset seizures was observed over the entire treatment period. The
      median partial-onset seizure count decreased from 2.3 per week during the
      baseline period to 1.3 per week over the treatment period. A total of 42.4% of
      patients were responders (> or = 50% reduction from baseline in weekly seizure
      frequency) over the treatment period; two patients were seizure-free from the
      first day of treatment throughout the treatment period. The most frequent drug
      related adverse events were fatigue (27.3% of patients), somnolence (11.1%),
      headache (8.1%), and dizziness (8.1%). CONCLUSION: Levetiracetam as add-on
      therapy at doses up to 3000 mg/day effectively reduced the frequency of partial
      onset seizures in patients with refractory epilepsy and was well-tolerated in
      this study, bridging conditions of placebo-controlled clinical trials and
      clinical practice.

PMID- 15716084
TI  - Codon bias as a factor in regulating expression via translation rate in the human
      genome.
AB  - We study the interrelations between tRNA gene copy numbers, gene expression
      levels and measures of codon bias in the human genome. First, we show that
      isoaccepting tRNA gene copy numbers correlate positively with expression-weighted
      frequencies of amino acids and codons. Using expression data of more than 14,000
      human genes, we show a weak positive correlation between gene expression level
      and frequency of optimal codons (codons with highest tRNA gene copy number).
      Interestingly, contrary to non-mammalian eukaryotes, codon bias tends to be high
      in both highly expressed genes and lowly expressed genes. We suggest that
      selection may act on codon bias, not only to increase elongation rate by favoring
      optimal codons in highly expressed genes, but also to reduce elongation rate by
      favoring non-optimal codons in lowly expressed genes. We also show that the
      frequency of optimal codons is in positive correlation with estimates of protein
      biosynthetic cost, and suggest another possible action of selection on codon
      bias: preference of optimal codons as production cost rises, to reduce the rate
      of amino acid misincorporation. In the analyses of this work, we introduce a new
      measure of frequency of optimal codons (FOP'), which is unaffected by amino acid
      composition and is corrected for background nucleotide content; we also introduce
      a new method for computing expected codon frequencies, based on the dinucleotide
      composition of the introns and the non-coding regions surrounding a gene.

PMID- 15716085
TI  - Evolutionary significance of gene expression divergence.
AB  - Recent large-scale studies of evolutionary changes in gene expression among
      mammalian species have led to the proposal that gene expression divergence may be
      neutral with respect to organismic fitness. Here, we employ a comparative
      analysis of mammalian gene sequence divergence and gene expression divergence to
      test the hypothesis that the evolution of gene expression is predominantly
      neutral. Two models of neutral gene expression evolution are considered: 1-purely
      neutral evolution (i.e., no selective constraint) of gene expression levels and
      patterns and 2-neutral evolution accompanied by selective constraint. With
      respect to purely neutral evolution, levels of change in gene expression between
      human-mouse orthologs are correlated with levels of gene sequence divergence that
      are determined largely by purifying selection. In contrast, evolutionary changes
      of tissue-specific gene expression profiles do not show such a correlation with
      sequence divergence. However, divergence of both gene expression levels and
      profiles are significantly lower for orthologous human-mouse gene pairs than for
      pairs of randomly chosen human and mouse genes. These data clearly point to the
      action of selective constraint on gene expression divergence and are inconsistent
      with the purely neutral model; however, there is likely to be a neutral component
      in evolution of gene expression, particularly, in tissues where the expression of
      a given gene is low and functionally irrelevant. The model of neutral evolution
      with selective constraint predicts a regular, clock-like accumulation of gene
      expression divergence. However, relative rate tests of the divergence among human
      mouse-rat orthologous gene sets reveal clock-like evolution for gene sequence
      divergence, and to a lesser extent for gene expression level divergence, but not
      for the divergence of tissue-specific gene expression profiles. Taken together,
      these results indicate that gene expression divergence is subject to the effects
      of purifying selective constraint and suggest that it might also be substantially
      influenced by positive Darwinian selection.

PMID- 15716086
TI  - Comparative analysis of two genomic regions among four strains of Buchnera
      aphidicola, primary endosymbiont of aphids.
AB  - Preliminary analysis of two selected genomic regions of Buchnera aphidicola BCc,
      the primary endosymbiont of the cedar aphid Cinara cedri, has revealed a number
      of interesting features when compared with the corresponding homologous regions
      of the three B. aphidicola genomes previously sequenced, that are associated with
      different aphid species. Both regions exhibit a significant reduction in length
      and gene number in B. aphidicola BCc, as it could be expected since it possess
      the smallest bacterial genome. However, the observed genome reduction is not even
      in both regions, as it appears to be dependent on the nature of their gene
      content. The region fpr-trxA, that contains mainly metabolic genes, has lost
      almost half of its genes (45.6%) and has reduced 52.9% its length. The reductive
      process in the region rrl-aroK, that contains mainly ribosomal protein genes, is
      less dramatic, since it has lost 9.3% of genes and has reduced 15.5% of its
      length. Length reduction is mainly due to the loss of protein-coding genes, not
      to the shortening of ORFs or intergenic regions. In both regions, G+C content is
      about 4% lower in BCc than in the other B. aphidicola strains. However, when only
      conserved genes and intergenic regions of the four B. aphidicola strains are
      compared, the G+C reduction is higher in the fpr-trxA region.

PMID- 15716087
TI  - Simple sequence repeats in proteins and their significance for network evolution.
AB  - Only 5-6% of mammalian genomes are genes; the remainders are made up primarily of
      transposable elements and different types of simple sequence repeat (SSRs) (micro
      and minisatellites and cryptic repeats), which tend to accumulate in organisms
      with larger genomes. SSRs are also found at the level of protein sequences and
      may or may not be encoded by SSRs at the DNA sequence level. Studies of proteins
      containing SSRs indicate that they tend to belong to particular functional
      classes, particularly transcription factors and protein kinases. Protein SSRs
      coded for by pure codon repeats evolve rapidly while those encoded by mixtures of
      codons evolve slowly. We outline a conceptualization of how protein SSRs may
      arise and become fixed in proteins during evolution, and suggest that emergence
      and change in length of protein SSRs may affect the topology of protein
      interaction networks.

PMID- 15716088
TI  - Generality of the structurally constrained protein evolution model: assessment on
      representatives of the four main fold classes.
AB  - The Structurally Constrained Protein Evolution (SCPE) model simulates protein
      evolution by introducing random mutations into the evolving sequences and
      selecting them against too much structural perturbation. Given a single protein
      structure, the SCPE model can be used to obtain a whole set of site-dependent
      amino acid substitution matrices. The set of SCPE substitution matrices for a
      given protein family can be seen as an independent-sites model of evolution for
      that family. Thus, these matrices can be compared with other substitution-matrix
      based models of evolution. So far, SCPE has been tested only on left-handed
      parallel beta helix (LbetaH) proteins. Here, we address the question of
      generality by assessing the SCPE model on representatives of the four main
      classes of folds: alpha, beta, alpha+beta, and alpha/beta. We compare with other
      models using the likelihood ratio test with parametric bootstrapping. We show
      that SCPE performs better than the popular JTT model for all cases considered.
      Furthermore, by considering the relative contributions of mutation and selection,
      we found that the key to the success of the SCPE model is the selection step.

PMID- 15716089
TI  - Phylogenetic and structural analysis of mitochondrial complex I proteins.
AB  - Our understanding of the evolutionary process would benefit from a better
      understanding of protein structural changes during evolution. I report that
      combining phylogenetic and structural analyses of the mitochondrial protein
      sequences allow to identify important differences between protostomes and
      deuterostomes mitochondrial proteins: (1) ND5, and with less intensity, ND1, ND2
      and ND4, have significantly lower hydrophobicity in deuterostomes than in
      proterostomes; (2) the C-terminal half portion of ND5 has lower hydrophobicity
      than the N-terminal half portion, suggesting the presence of larger extra
      membrane hydrophilic loops in deuterostomes with respect to protostomes; (3)
      substitution matrices generated from different complex I proteins show different
      patterns of amino acid substitutions, suggesting that mitochondrial proteins have
      different evolutionary dynamics. I hypothesise that the better performances in
      phylogenetic inference of ND5 with respect to other mitochondrial proteins may be
      related to its position inside the complex I.

PMID- 15716090
TI  - Fish and mammalian metallothioneins: a comparative study.
AB  - Structural studies show that fish and mammalian metallothioneins are endowed of
      distinctive features. In particular, the ninth cysteine residue present in the
      alpha domain of fish metallothionein is shifted of two positions with respect to
      the mammalian metallothionein, introducing a conformational modification in the
      protein structure. In addition, the fish metallothionein is less hydrophobic and
      more flexible than its mammalian counterpart. Our previous studies showed that
      the hydropathy of piscine and mammalian metallothioneins is significantly
      correlated with organismal temperature. In the present paper we have performed
      phylogenetic comparative analysis on metallothioneins of 24 species of fish and
      mammals. The results of such analysis failed to indicate that metallothionein
      hydropathy is an adaptive response to the thermal regime of the species. We
      concluded that metallothionein hydropathy is a trait that did not evolve in
      association with environmental changes.

PMID- 15716091
TI  - Transposable elements as a source of genetic innovation: expression and evolution
      of a family of retrotransposon-derived neogenes in mammals.
AB  - A family of functional neogenes called Mart, related to the gag gene of Sushi
      like long terminal repeat retrotransposons from fish and amphibians, is present
      in the genome of human (11 genes) and other primates, as well as in mouse (11
      genes), rat, dog (12 genes), cat, and cow. Mart genes have lost their capacity of
      retrotransposition through non-functionalizing rearrangements having principally
      affected long terminal repeats and pol open reading frame. Most Mart genes are
      located on the X chromosome in different mammals. Sequence database analysis
      suggested that Mart genes are present in opossum (marsupial), but absent from the
      genome of chicken. Hence, the Mart gene family might have been formed from Sushi
      like retrotransposon(s) after the split of birds and mammals (310 myr ago), but
      before the divergence between placental mammals and marsupials (170 myr ago). RT
      PCR analysis showed that at least six Mart genes are expressed during mouse
      embryonic development, with in situ hybridization analysis revealing rather
      ubiquitous expression patterns. Mart expression was also detected in adult mice,
      with some genes being expressed in all tissues tested, while others showed a much
      more restricted expression pattern. Although additional analysis will be required
      to establish the function of the retrotransposon-derived Mart neogenes, these
      observations support the evolutionary importance of retrotransposable elements as
      a source of genetic novelty.

PMID- 15716092
TI  - Mutation and selection on the anticodon of tRNA genes in vertebrate mitochondrial
      genomes.
AB  - The H-strand of vertebrate mitochondrial DNA is left single-stranded for hours
      during the slow DNA replication. This facilitates C-->U mutations on the H-strand
      (and consequently G-->A mutations on the L-strand) via spontaneous deamination
      which occurs much more frequently on single-stranded than on double-stranded DNA.
      For the 12 coding sequences (CDS) collinear with the L-strand, NNY synonymous
      codon families (where N stands for any of the four nucleotides and Y stands for
      either C or U) end mostly with C, and NNR and NNN codon families (where R stands
      for either A or G) end mostly with A. For the lone ND6 gene on the other strand,
      the codon bias is the opposite, with NNY codon families ending mostly with U and
      NNR and NNN codon families ending mostly with G. These patterns are consistent
      with the strand-specific mutation bias. The codon usage biased towards C-ending
      and A-ending in the 12 CDS sequences affects the codon-anticodon adaptation. The
      wobble site of the anticodon is always G for NNY codon families dominated by C
      ending codons and U for NNR and NNN codon families dominated by A-ending codons.
      The only, but consistent, exception is the anticodon of tRNA-Met which
      consistently has a 5'-CAU-3' anticodon base-pairing with the AUG codon (the
      translation initiation codon) instead of the more frequent AUA. The observed CAU
      anticodon (matching AUG) would increase the rate of translation initiation but
      would reduce the rate of peptide elongation because most methionine codons are
      AUA, whereas the unobserved UAU anticodon (matching AUA) would increase the
      elongation rate at the cost of translation initiation rate. The consistent CAU
      anticodon in tRNA-Met suggests the importance of maximizing the rate of
      translation initiation.

PMID- 15716094
TI  - Evolution of human IgH3'EC duplicated structures: both enhancers HS1,2 are
      polymorphic with variation of transcription factor's consensus sites.
AB  - The enhancer complex regulatory region at the 3' of the immunoglobulin heavy
      cluster (IgH3'EC) is duplicated in apes along with four constant genes and the
      region is highly conserved throughout humans. Both human IgH3'ECs consist of
      three loci high sensitive (HS) to DNAse I with enhancer activity. It is thus
      possible that the presence of structural divergences between the two IgH3'ECs and
      of relative polymorphisms correspond to functional regulatory changes. To analyse
      the polymorphisms of these almost identical regions, it resulted mandatory to
      identify the presence of divergent sequences, in order to select distinctive
      primers for specific PCR genomic amplifications. To this aim, we first compared
      the two entire IgH3'ECs in silicio, utilising the updated GenBank (GB) contigs,
      then we analysed the two IgH3'ECs by cloning and sequencing amplicons from
      independent genomes. In silicio analysis showed that several inversions,
      deletions and short insertions had occurred after the duplication. We analysed in
      detail, by sequencing specific regions, the polymorphisms occurring in enhancer
      HS1,2-A (which lies in IgH3'EC-1, 3' to the Calpha-1 gene) and in enhancer HS1,2
      B (which lies in IgH3'EC-2, 3' to Calpha-2). Polymorphisms are due to the
      repetition (occurring one to four times) of a 38-bp sequence present at the 3' of
      the core of enhancers HS1,2. The structure of both human HS1,2 enhancers has
      revealed not yet described polymorphic features due to the presence of variable
      spacer elements separating the 38-bp repetitions and to variable external
      elements bordering the repetition cluster. We found that one of the external
      elements gave rise to a divergent allele 3 in the two clusters. The frequency of
      the different alleles of the two loci varies in the Italian population and allele
      3 of both loci are very rare. The analysis of the Callicebus moloch, Gorilla
      gorilla and Pan troglodytes HS1,2 enhancers showed the transformation from the
      ancestral structure with the 31- to the 17-bp external element in hominids. The
      relevance of the polymorphisms in the HS1,2 enhancers is due to the variable
      number of binding sites for the transcription factors: NF-kappaB, CMYB, BSAP1/2,
      AP1/4, E47, MyoD and muE5 and thus to the possible influence of these variations
      on switch, production of Ig and on maturation of B cells.

PMID- 15716093
TI  - Upf1p, a highly conserved protein required for nonsense-mediated mRNA decay,
      interacts with the nuclear pore proteins Nup100p and Nup116p.
AB  - Saccharomyces cerevisiae Upf1p is a 971-amino-acid protein that is required for
      the nonsense-mediated mRNA decay (NMD) pathway, a pathway that degrades mRNAs
      with premature translational termination codons. We have identified a two-hybrid
      interaction between Upf1p and the nuclear pore (Nup) proteins, Nup100p and
      Nup116p. Both nucleoporins predominantly localize to the cytoplasmic side of the
      nuclear pore and participate in mRNA transport. The two-hybrid interaction
      between Upf1p and the nuclear pore proteins, Nup100p and Nup116p, is dependent on
      the presence of the C-terminal 158 amino acids of Upf1p. Nup100p and Nup116p can
      be co-immunoprecipitated from whole-cell extracts with Upf1p, confirming in vitro
      the interaction identified by the two-hybrid analysis. Finally, we see a genetic
      interaction between UPF1 and NUP100. The growth of upf1Delta, can1-100 cells is
      inhibited by canavanine. The deletion of NUP100 allows upf1Delta, can1-100 cells
      to grow in the presence of canavanine. Physiologically, the interaction between
      Upf1p and the nuclear pore proteins, Nup100p and Nup116p, is significant because
      it suggests a mechanism to ensure that Upf1p associates with newly synthesized
      mRNA as it is transported from the nucleus to the cytoplasm prior to the pioneer
      round of translation.

PMID- 15716095
TI  - The ocean abysses witnessed the origin of the genetic code.
AB  - The comparison of proteins from a non-barophilous and a barophilous organism
      makes it possible to define the barophily ranks of amino acids. The correlation
      of these ranks with the number of codons attributed to amino acids in the genetic
      code, together with another straightforward argument based on an optimisation
      percentage of a barophily index (BI) (easily defined by barophily ranks) which
      can be associated to the genetic code table, suggest that the genetic code
      originated under high hydrostatic pressure. Moreover, as the BI value can be
      calculated for the sequence of any protein, it also makes it possible to define
      the BI for the genetic code if the number of codons attributed to the amino acids
      in the code is assumed to be the frequency with which the amino acids appeared in
      ancestral proteins. Finally, sampling the BI variable between many non-barophile
      organisms and from many proteins of a single non-barophile organism leads to the
      conclusion that the BI value of the genetic code is not typical of these
      organisms. Whereas, since the genetic code BI value is statistically higher than
      that of these non-barophile organisms, it supports the hypothesis that genetic
      code structuring took place under high hydrostatic pressure.

PMID- 15716096
TI  - A comparison of proteins from Pyrococcus furiosus and Pyrococcus abyssi:
      barophily in the physicochemical properties of amino acids and in the genetic
      code.
AB  - A comparison is made between orthologous proteins from a nonbarophile (Pyrococcus
      furiosus) and a barophile (Pyrococcus abyssi) organism. The pattern of
      asymmetries in the amino acid substitution process identifies the amino acids
      arginine, serine, glycine, valine and aspartic acid as those having the most
      barophilic behaviour, and tyrosine and glutamine as the least barophilic. The
      construction of a hydrostatic pressure asymmetry index (PAI) which orders the
      amino acids from the most barophilic to the least barophilic makes it possible to
      visualise the amino acid properties that best explain barophily. The polarity of
      amino acids is positively correlated to the PAI values, i.e., on average, the
      more polar amino acids possess a higher PAI value, that is to say they are more
      barophilic. Moreover, the "size" of amino acids (molecular weight) is negatively
      correlated to the PAI value, that is to say that, on average, high PAI values are
      associated to "small" amino acids which are therefore more barophilic than
      "larger" ones. These two amino acid properties are the same ones that are known
      for having been important in affecting the origin of genetic code organisation.
      All the above, as well as the significant and positive correlation between the
      number of codons attributed to the amino acids in the genetic code and the PAI
      values, seem to favour the hypothesis that genetic code structuring took place
      under high hydrostatic pressure.

PMID- 15716097
TI  - The 350-fold compacted Fugu parkin gene is structurally and functionally similar
      to human Parkin.
AB  - Mutations in the human parkin gene (huParkin) are the predominant genetic cause
      of familial parkinsonism. The huParkin locus, spanning about 1.4 Mb, is one of
      the largest in the human genome. Despite its huge size, huParkin codes for a
      rather short transcript of about 4.5 kb. To gain an insight into the structure,
      function and evolutionary history of huParkin, we have characterized the
      pufferfish [Fugu rubripes (Fugu)] ortholog of huParkin. A remarkable feature of
      the Fugu parkin gene (fuparkin) is its unusually compact size. It spans only
      about 4 kb and is thus 350-fold smaller than its human ortholog. The Fugu and
      human parkin genes are otherwise highly similar in their genomic organization and
      expression pattern. Furthermore, like human Parkin, Fugu parkin also functions as
      an ubiquitin ligase. These shared features between fuparkin and huParkin suggest
      that the physiological function and regulation of the parkin gene are conserved
      during the evolution of vertebrates. Conceivably, the compact locus of fuparkin
      could serve as a useful model to understand the transcriptional regulation of
      huParkin.

PMID- 15716098
TI  - The fmo genes of Caenorhabditis elegans and C. briggsae: characterisation, gene
      expression and comparative genomic analysis.
AB  - The flavin-containing monooxygenase (FMO) gene family is conserved and ancient
      with representatives present in almost all phyla so far examined. The genes
      encode FAD-, NADP- and O(2)-dependent enzymes that catalyse oxygenation of soft
      nucleophilic heteroatom centres in a range of substrates. Although usually
      classified as xenobiotic-metabolising enzymes, examples of FMOs exist that have
      evolved to metabolise specific endogenous substrates as part of a discrete
      physiological process. The genome of Caenorhabditis elegans contains five
      predicted genes encoding putative homologs of mammalian FMOs, K08C7.2, K08C7.5,
      Y39A1A.19, F53F4.5 and H24K24.5, which we have named fmo and numbered fmo-1 to
      fmo-5, respectively. As a first step towards determining their functional
      role(s), we have experimentally characterised these C. elegans fmo genes
      including analysing reporter gene expression patterns and RNAi phenotypes. Two
      major gene expression patterns were observed, either intestinal or hypodermal,
      but no gross RNAi phenotypes were found possibly due to functional redundancy.
      The internal structures of fmo-2, fmo-3 and fmo-4 have been compared with
      orthologs identified in the related nematode C. briggsae. For each orthologous
      pair, a global comparison of the paired upstream intergenic regions was performed
      and a number of conserved noncoding sequences, which may represent potential cis
      regulatory elements, identified. Phylogenetic analysis reveals that several of
      the fmo homologs are the result of gene duplication along the lineage leading to
      the nematodes.

PMID- 15716100
TI  - In vivo RNA-RNA duplexes from human alpha3 and alpha5 nicotinic receptor subunit
      mRNAs.
AB  - Natural antisense transcripts, because of their potential to form double-stranded
      RNA (dsRNA) molecules, recently emerged as a mechanism acting on eukaryotic gene
      regulation at multiple levels. CHRNA3 and CHRNA5, coding for alpha3 and alpha5
      subunits of the neuronal nicotinic acetylcholine receptor, have been reported to
      overlap at their 3'ends in human and bovine genomes. In the present paper, four
      CHRNA3 and three CHRNA5 human transcripts were characterised, leading to the
      identification of different antisense complementary regions. Since the two genes
      are coexpressed in some neuronal and non-neuronal tissues, we ventured on the in
      vivo identification of RNA-RNA duplexes in both humans and cattle. Using an RNase
      protection-based approach, CHRNA3/CHRNA5 duplexes were detected in human
      neuroblastoma SY5Y cells, but not in bovine cerebellum. A semi-quantitative
      analysis of overlapping transcript levels was performed by real-time RT-PCR.
      Possible consequences of sense-antisense interaction are discussed.

PMID- 15716099
TI  - Evolutionary changes of the number of olfactory receptor genes in the human and
      mouse lineages.
AB  - The numbers of functional olfactory receptor (OR) genes are quite variable among
      mammalian species. Previously we have reported that humans have 388 functional OR
      genes and 414 pseudogenes, while mice have 1037 functional genes and 354
      pseudogenes. These observations suggest either that humans lost many functional
      OR genes after the human-mouse divergence (HMD) or that mice gained many
      functional genes. To distinguish between these two hypotheses, we devised a new
      method of inferring the number of functional OR genes in the most recent common
      ancestor (MRCA) of humans and mice. An application of this method suggested that
      the MRCA had approximately 750 functional OR genes and that mice acquired
      approximately 350 new OR genes after the HMD whereas approximately 430 OR genes
      in the MRCA have become pseudogenes or eliminated in the human lineage.
      Therefore, the two evolutionary hypotheses mentioned above are not mutually
      exclusive and both are nearly equally responsible for the difference in the
      number of OR genes between humans and mice.

PMID- 15716101
TI  - Comparative analysis of gene sequence of goat CSN1S1 F and N alleles and
      characterization of CSN1S1 transcript variants in mammary gland.
AB  - In this paper, we report the full characterization, at DNA and RNA level, of the
      defective goat CSN1S1 F and N alleles and an extensive comparison with the A
      allele counterpart. By utilizing genomic DNA as template, we amplified the whole
      CSN1S1 gene plus 1972/3 nucleotides of the 5' region plus 610 nucleotides of the
      3' region of the goat CSN1S1 N and CSN1S1 F alleles. Comparison of sequences of
      the N, F and A CSN1S1 alleles showed a total of 118 polymorphic sites. In
      particular, both the N and the F alleles are characterized by a deletion of the
      cytosine at the 23rd nucleotide of the 9th exon. The resulting one-nucleotide
      frameshift determines a premature stop codon (TGA, nucleotides 17-19 of the 12th
      exon). On the basis of the information so far available, it seems reasonable to
      hypothesize that the CSN1S1 N allele might be originated by interallelic
      recombination events. Comparison of transcripts produced by the N and F alleles
      shows a remarkable variability in alternative splicing events which concern, even
      though with different percentage ratios, mainly the lack of the 9th exon, the
      deletion of the last 5 nucleotides of the 9th exon and the contemporary deletion
      of exons 10 and 11.

PMID- 15716102
TI  - Molecular cloning and characterization of a new RGS protein of Medaka.
AB  - We identified eight genes of putative RGS proteins in skin of Medaka fish using
      PCR amplification with degenerate primers for the RGS domain of known RGS
      proteins. Then, we cloned a full-length cDNA for a new RGS protein. This RGS
      protein was similar to human RGS3 within the RGS domain, but other parts were
      unique among known RGS proteins. RT-PCR analysis demonstrated that this Medaka
      RGS3-like protein (MeRGS3L) is mainly expressed in skin and heart. When
      coexpressed in Xenopus oocytes, MeRGS3L accelerated the turning-on and -off of
      Gi/o-mediated modulation of GIRK channels without apparent desensitization in the
      presence of ligand. MeRGS3L also decreased the response of Gq signaling upon
      activation of m1 muscarinic receptor. This new RGS protein may play important
      roles in regulation of melanophore responses in Medaka skin.

PMID- 15716103
TI  - Newly sequenced eRF1s from ciliates: the diversity of stop codon usage and the
      molecular surfaces that are important for stop codon interactions.
AB  - The genetic code of nuclear genes in some ciliates was found to differ from that
      of other organisms in the assignment of UGA, UAG, and UAA codons, which are
      normally assigned as stop codons. In some ciliate species, the universal stop
      codons UAA and UAG instead encode glutamine. In some other ciliates, the
      universal stop codon UGA appears to be translated as cysteine or tryptophan.
      Eukaryotic release factor 1 (eRF1) is a key protein in stop codon recognition,
      thus, the protein is believed to play an important role in the stop codon
      reassignment in ciliates. We have cloned, sequenced, and analyzed the cDNA of
      eRF1 from four ciliate species of three different classes: Karyorelictea (Loxodes
      striatus), Heterotrichea (Blepharisma musculus), and Litostomatea (Didinium
      nasutum, Dileptus margaritifer). Phylogenetic analysis of these eRF1s supports
      the hypothesis that the genetic code in ciliates has deviated independently
      several times from the universal genetic code, and that different ciliate eRF1s
      may have undergone different processes to change the codon specificity. Using
      computational methods, we have also suggested areas on the surface of eRF1s that
      are important for stop codon recognition in ciliate eRF1s.

PMID- 15716104
TI  - Determination of gaps by contig alignment with telomere-mediated chromosomal
      fragmentation in Candida albicans.
AB  - We have adopted a method of telomere-mediated chromosome fragmentation in order
      to demonstrate the alignment of contigs and determination of gaps. We established
      the order and orientation of four contigs of Candida albicans chromosome 5 and
      determined the sizes of three gaps between these contigs. We confirmed this
      proposed alignment of contigs, as well as gap sizes, by sequencing one gap and
      analyzing three mega deletions of approximately 41 kbp, 58 kbp, and 77 kbp, which
      covered two other gaps. These gaps could be also conveniently sequenced, which is
      an important step in establishing a complete sequence. The combined length of
      contigs and gaps covered approximately 422 kbp, which is one third of chromosome
      5. Telomere-mediated chromosome fragmentation, used here for the first time to
      align the contigs of C. albicans and determine the gaps, proved to be a reliable
      method. The method could be helpful in sequencing projects of other diploid
      organisms, in particular those in which centromeres have not been identified. In
      addition, our approach can be used to assign any contig to a chromosome, or to
      induce the loss of a specific chromosome.

PMID- 15716105
TI  - Translation initiation factor (iso) 4E interacts with BTF3, the beta subunit of
      the nascent polypeptide-associated complex.
AB  - A two-hybrid screen with the translation initiation factor, eIF(iso)4E from
      Arabidopsis, identified a clone encoding a lipoxygenase type 2 [Freire, M.A., et
      al., 2000. Plant lipoxygenase 2 is a translation initiation factor-4E-binding
      protein. Plant Molecular Biology 44, 129-140], and three cDNA clones encoding the
      homologue of the mammalian BTF3 factor, the beta subunit of the nascent
      polypeptide-associated complex (NAC). Here we report on the interaction between
      the translation initiation factor eIF(iso)4E and AtBTF3. AtBTF3 protein is able
      to interact with the wheat initiation factors eIF4E and eIF(iso)4E. AtBTF3
      contains a sequence related to the prototypic motif found on most of the 4E
      binding proteins, and competes with the translation initiation factor eIF(iso)4G
      for eIF4(iso)4E binding, in a two hybrid interference assay. These findings
      provide a molecular link between the translation initiation mechanism and the
      emergence of the nascent polypeptide chains.

PMID- 15716106
TI  - Quantitative PCR analysis of two molluscan metallothionein genes unveils
      differential expression and regulation.
AB  - The mRNA levels of two components of the mussel (Mytilus galloprovincialis)
      metallothionein (MT) gene families, MT10 and MT20, were evaluated using real-time
      quantitative-PCR and Sybr Green I chemistry in animals exposed to heavy metals in
      vivo and in primary cell cultures. This method was highly specific in detecting
      the expression of the two genes over a widely dynamic range of starting DNA
      amounts, showing that the basal level of MT expression is mostly due to MT10
      mRNA. Basal MT expression reflected the intracellular concentration of heavy
      metal as indicated by the use of the heavy metal chelator TPEN on primary cells.
      MT10 was observed to be inducible by Cd, Zn, and Cu ions, and to a lesser extent
      by Hg. By contrast, the MT20 expression level was very low under basal
      conditions, while its mRNA increased dramatically in response to Cd exposure, and
      to a lesser extend to Hg, leading to levels of expression similar to those of the
      MT10 gene. The essential metals Cu and Zn had a very small effect on the MT20
      gene, whereas the concomitant exposure to Cu and H(2)O(2) produced a rapid rise
      of expression. In summary, data indicate that the MT isogenes are differentially
      regulated by heavy metals, while hydroxyl radicals may have a role in MT20 gene
      activation. Also, protein expression showed metal inducibility only after Cd
      exposure, suggesting the occurrence of posttranscriptional control mechanisms.

PMID- 15716107
TI  - Identification and characterization of the promoter for the gene encoding human
      tripeptidyl-peptidase II.
AB  - Tripeptidyl-peptidase II (TPP II) is a ubiquitously expressed exopeptidase. The
      expression of this enzyme is increased, e.g. in some tumor cells, but the
      regulation of the expression of the gene has not been investigated previously.
      The gene encoding human TPP II (TPP2) is 82 kb and consists of 30 exons. An 8 kb
      NcoI fragment covering the 5'-flanking region of the TPP2 gene, including the
      initiation codon, was cloned into a luciferase-containing reporter vector. Human
      embryonic kidney cells (HEK-293 cells) and murine fibroblasts (NIH3T3 cells) were
      transiently transfected with the construct. Through sequential deletions and
      analysis of short PCR-fragments, the promoter could be localized to a 215 bp
      fragment upstream of the initiation codon. This region is GC-rich, lacks a TATA
      box and contains two inverted CCAAT-boxes and a GC-box. Electrophoretic mobility
      shift assays showed that nuclear proteins bind to the promoter fragment. The 85
      bp 5'-end of the promoter fragment is essential for transcriptional activation.
      Out of this a 44 bp fragment suffices to compete with binding of nuclear proteins
      to the 215 bp fragment. Supershift assays demonstrated that the CCAAT-binding
      factor (CBF; NF-Y) is involved in the formation of a complex with the 215 bp
      fragment. Although Sp1 binds to the promoter fragment in vitro, it was found to
      bind to the 3'-end of the 215 bp fragment which is not essential for
      transcription. The potential role of Sp1 in transcription of TPP2 therefore
      remains to be established.

PMID- 15716108
TI  - Carotenoid biosynthetic pathway: molecular phylogenies and evolutionary behavior
      of crt genes in eubacteria.
AB  - Phylogenetic analysis of carotenoid biosynthetic pathway genes and their
      evolutionary rate variations were studied among eubacterial taxa. The gene
      sequences for the enzymes involved in this pathway were obtained for major
      phylogenetic groups of eubacteria (green sulfur bacteria, green nonsulphur
      bacteria, Gram-positive bacteria, proteobacteria, flavobacteria, cyanobacteria)
      and archeabacteria. These gene datasets were distributed under five major steps
      of carotenoid biosynthesis in eubacteria; isoprenoid precursor biosynthesis,
      phytoene synthesis, dehydrogenation of phytoene, lycopene cyclization, formation
      of acyclic xanthophylls, formation of cyclic xanthophylls and carotenoid
      biosynthesis regulation. The NJ algorithm was used on protein coding DNA
      sequences to deduce the evolutionary relationship for the respective crt genes
      among different eubacterial lineages. The rate of nonsynonymous nucleotide
      substitutions per nonsynonymous site (d(N)) and synonymous nucleotide
      substitutions per synonymous site (d(S)) were calculated for different clades of
      the respective phylogenetic tree for specific crt genes. The phylogenetic
      analysis suggests that evolutionary pattern of crt genes in eubacteria is
      characterized by lateral gene transfer and gene duplication events. The d(N)
      values indicate that carotenoid biosynthetic genes are more conserved in
      proteobacteria than in any other eubacterial phyla. Furthermore, of the genes
      involved in carotenoid biosynthesis pathway, structural genes evolve slowly than
      the regulatory genes in eubacteria.

PMID- 15716109
TI  - The effect of RNA secondary structures on RNA-ligand binding and the modifier RNA
      mechanism: a quantitative model.
AB  - RNA-ligand binding often depends crucially on the local RNA secondary structure
      at the binding site. We develop here a model that quantitatively predicts the
      effect of RNA secondary structure on effective RNA-ligand binding activities
      based on equilibrium thermodynamics and the explicit computations of partition
      functions for the RNA structures. A statistical test for the impact of a
      particular structural feature on the binding affinities follows directly from
      this approach. The formalism is extended to describing the effects of hybridizing
      small "modifier RNAs" to a target RNA molecule outside its ligand binding site.
      We illustrate the applicability of our approach by quantitatively describing the
      interaction of the mRNA stabilizing protein HuR with AU-rich elements. We discuss
      our model and recent experimental findings demonstrating the effectivity of
      modifier RNAs in vitro in the context of the current research activities in the
      field of non-coding RNAs. We speculate that modifier RNAs might also exist in
      nature; if so, they present an additional regulatory layer for fine-tuning gene
      expression that could evolve rapidly, leaving no obvious traces in the genomic
      DNA sequences.

PMID- 15716110
TI  - The compositional transition of vertebrate genomes: an analysis of the secondary
      structure of the proteins encoded by human genes.
AB  - Fluctuations and increments of both C(3) and G(3) levels along the human coding
      sequences were investigated comparing two sets of Xenopus/human orthologous
      genes. The first set of genes shows minor differences of the GC(3) levels, the
      second shows considerable increments of the GC(3) levels in the human genes. In
      both data sets, the fluctuations of C(3) and G(3) levels along the coding
      sequences correlated with the secondary structures of the encoded proteins. The
      human genes that underwent the compositional transition showed a different
      increment of the C(3) and G(3) levels within and among the structural units of
      the proteins. The relative synonymous codon usage (RSCU) of several amino acids
      were also affected during the compositional transition, showing that there exists
      a correlation between RSCU and protein secondary structures in human genes. The
      importance of natural selection for the formation of isochore organization of the
      human genome has been discussed on the basis of these results.

PMID- 15716111
TI  - Estimation of ancestral gene set of bilaterian animals and its implication to
      dynamic change of gene content in bilaterian evolution.
AB  - To understand the process of bilaterian evolution, we estimated ancestral gene
      sets at the split of plant-animal-fungi and the divergence of bilaterian animals
      and from 1,236,790 non-redundant genes. We, then, examined how the numbers of the
      gene clusters have changed since the split. As a result, we estimated the numbers
      of gene clusters in the ancestral gene sets of plant-animal-fungi and bilaterian
      animals to be at least 2469 and 6577, respectively. Thus, we found a 2.7-fold
      increase in the number of gene clusters during the period from the evolutionary
      split of plant-animal-fungi to the divergence of bilaterian animals. Moreover,
      when we compared these numbers of ancestral gene clusters with those of extant
      animals such as the nematode, fly, mouse and human, we found that the extant
      bilaterian animals have retained more than 3500 gene clusters of the ancestral
      gene set, and have lost more than 1600 gene clusters. It suggests that these
      processes of genomic diversification provided bilaterian animals with molecular
      basis for species diversity.

PMID- 15716112
TI  - Characterization of the human P-type 6-phosphofructo-1-kinase gene promoter in
      neural cell lines.
AB  - In humans three isoforms of 6-phosphofructo-1-kinase (PFK) exist. Among them
      platelet-type PFK (PFKP) is highly abundant in the brain. With its distinct
      allosteric properties PFKP is regarded to be the key enzyme for the regulation of
      glycolysis in this organ. We cloned 1.7 kb of the 5' upstream promoter of the
      human PFKP gene and analyzed the promoter activity by deletion and mutation
      analysis using a luciferase reporter. The transcription start point was
      determined at 48 bp upstream of the start codon. In deletion studies the region 
      65 to +48 turned out to be sufficient for promoter activity while fragment -153
      to +48 showed the highest promoter activity. Sequence analysis of the region from
      -153 to +48 revealed a stretch of eight adjacent putative transcription factor
      binding sites, seven of which are Sp-family specific sites. Sp1 and Sp3 were
      shown to bind to most if not all of them. Additionally, an NF-Y binding site was
      identified. Results of deletion and mutation analysis suggest that all of these
      transcription factors contribute positively to promoter activity. The methylation
      status of the promoter region was analyzed in different neural tumor cell lines
      and compared with that in human leukocytes and muscle.

PMID- 15716113
TI  - Cellular expression and alternative splicing of SLC25A23, a member of the
      mitochondrial Ca2+-dependent solute carrier gene family.
AB  - The transport of metabolites across the inner mitochondrial membrane is mediated
      by a large superfamily of mitochondrial solute carrier (MSC) proteins. A novel
      human member of the MSC gene family named SLC25A23, with homologs in mammalian
      and non-mammalian species has been recently identified together with two close
      paralogs, SLC25A24 and SLC25A25. These genes encode the human isoforms of the ATP
      Mg/Pi carrier described in whole mitochondria. We report here the cellular
      expression and alternative splicing of SLC25A23. The gene encodes a 468 amino
      acids polypeptide, named SCaMC-3, with a bipartite structure typical of calcium
      binding mitochondrial solute carrier (CaMSC) proteins. The amino-terminal portion
      harbors three canonical EF-hand calcium-binding domains while the carboxyl
      terminal portion of SCaMC-3 has the characteristic features of the MSC
      superfamily. Northern blot analysis reveals the presence of the transcript in
      brain, heart, skeletal muscle, liver and small intestine. The SLC25A23 gene
      undergoes alternative splicing suggesting a modular nature of the encoded
      product. Three out of four putative protein isoforms lack a significant portion
      of the third mitochondrial carrier signature. The most common SCaMC-3 isoform
      shows a mitochondrial subcellular localization when transfected in HeLa cells and
      is able to bind calcium by Ca(2+)-dependent mobility shift assays. We believe
      that our study will contribute to a better knowledge of this family of
      mitochondrial carriers.

PMID- 15716114
TI  - Interactions between CCAAT enhancer binding protein delta and estrogen receptor
      alpha control insulin-like growth factor I (igf1) and estrogen receptor-dependent
      gene expression in osteoblasts.
AB  - Although ambient levels of estradiol and synthesis of the osteoblast growth
      factor IGF-I are inversely related in vivo, estradiol has little or no direct
      effect on igf1 gene expression in rat osteoblasts in vitro. Rather, estradiol
      suppresses the effect of hormones that enhance igf1 expression through protein
      kinase A dependent activation of CCAAT enhancer binding protein (C/EBP)
      transcription factors. We show here that inhibition of C/EBP activity by
      estradiol relates to the level of estrogen receptor alpha (ERalpha) expression,
      and that a complex between hormone-activated ERalpha and C/EBPdelta inhibits
      transcription by each factor. Protein fragmentation, co-immunoprecipitation, and
      gene expression studies identified domains for physical and functional
      interactions between ERalpha and C/EBPdelta. Whereas ERalpha and fragments
      comprising its various domains associated with C/EBPdelta, only ERalpha fragment
      A/B alone replicated the suppressive effect of intact ERalpha on endogenous
      C/EBPdelta activity. Complementary studies showed that several carboxyl regions
      of C/EBPdelta cooperatively inhibit ERalpha dependent transcription. Therefore,
      multiple domains of C/EBPdelta and ERalpha can physically interact to alter gene
      expression in osteoblasts in selective ways that depend on variations in the
      local hormone environment. Their combined effects on one important gene target,
      igf1, may help to determine the balance in the overall rates of bone formation.

PMID- 15716116
TI  - Information theory reveals large-scale synchronisation of statistical
      correlations in eukaryote genomes.
AB  - We study short-range correlations in DNA sequences with methods from information
      theory and statistics. We find a persisting degree of identity between the
      correlation patterns of different chromosomes of a species. Except for the case
      of human and chimpanzee inter-species differences in this correlation pattern
      allow robust species distinction: in a clustering tree based upon the correlation
      curves on the level of individual chromosomes distinct clusters for the
      individual species are found. This capacity of distinguishing species persists,
      even when the length of the underlying sequences is drastically reduced. In
      comparison to the standard tool for studying symbol correlations in DNA
      sequences, namely the mutual information function, we find that an autoregressive
      model for higher order Markov processes significantly improves species
      distinction due to an implicit subtraction of random background.

PMID- 15716115
TI  - In silico diagnosis of inherently inhibited gene expression focusing on initial
      codon combinations.
AB  - The translation start site, immediately downstream from the start codon, is a
      dominant factor for gene expression in Escherichia coli. At present, no method
      exists to improve the expression level of cloned genes, since it remains
      difficult to find the best codon combination within the region. We determined the
      expression parameters that correspond to all sense codons within the first four
      codons using GFPuv which encodes a derivative of green fluorescent protein. Using
      a genetic algorithm (GA)-based computer program, these parameters were
      incorporated in a simple, static model for the prediction of translation
      efficiency, and optimized to the expression level for 137 randomly isolated GFPuv
      genes. The calculated initial translation index (ITI), also proven for the DsRed2
      gene that encodes a red fluorescent protein, should provide a solution to
      overcome the gene expression problem in cloned genes whose expression is often
      inherently blocked at the translation process. The proposed method facilitates
      heterologous protein production in E. coli, the most commonly used host in
      biological and industrial fields.

PMID- 15716117
TI  - A 21st century view of evolution: genome system architecture, repetitive DNA, and
      natural genetic engineering.
AB  - The last 50 years of molecular genetics have produced an abundance of new
      discoveries and data that make it useful to revisit some basic concepts and
      assumptions in our thinking about genomes and evolution. Chief among these
      observations are the complex modularity of genome organization, the biological
      ubiquity of mobile and repetitive DNA sequences, and the fundamental importance
      of DNA rearrangements in the evolution of sequenced genomes. This review will
      take a broad overview of these developments and suggest some new ways of thinking
      about genomes as sophisticated informatic storage systems and about evolution as
      a systems engineering process.

PMID- 15716118
TI  - Identification of genes expressed during Drosophila melanogaster gastrulation by
      using subtractive hybridization.
AB  - A subtractive hybridization approach was used to identify genes that are
      expressed at the beginning of gastrulation. We used tester DNA complimentary to
      RNA (cDNA) prepared from stages 6-7 embryos (gastrula) and excess driver cDNA
      from stages 2-4 embryos (syncytial blastoderm) to generate a gastrula-subtracted
      cDNA library. A reverse Northern blot procedure used to analyze 105 subtracted
      clones showed that 65% had a level of expression at least 2.5-fold higher in
      stages 6-7 versus stages 2-4 embryos. We determined the nucleotide sequence of
      these clones and identified 49 individual sequences, including 33 previously
      uncharacterized genes. We verified the level of expression of 24 genes during
      Drosophila melanogaster embryogenesis using a semiquantitative polymerase chain
      reaction (PCR) approach. As expected, all of the selected clones showed their
      highest level of expression after stages 2-4 of embryogenesis, including several
      that displayed peaks of expression during gastrulation. Three genes that were
      expressed at their highest levels in stages 6-7 were further analyzed by 5'-rapid
      amplification of cDNA ends (RACE) analysis, Northern blot assays and in situ
      hybridization. Our results indicate that these genes exhibited temporal and
      spatially restricted patterns of expression in developing embryos, and moreover,
      their transcripts were detected in cells that undergo morphological changes
      during the gastrulation stage. Characterizing the role of these genes will be
      important to increase our understanding of the molecular mechanisms that regulate
      cellular activities during D. melanogaster gastrulation.

PMID- 15716119
TI  - Expression of a xyloglucan endotransglucosylase/hydrolase gene, Mt-XTH1, from
      Medicago truncatula is induced systemically in mycorrhizal roots.
AB  - Xyloglucan endotransglucosylase/hydrolases (XTH) are enzymes that catalyze the
      hydrolysis and transglycosylation of xyloglucan polymers in plant cell walls.
      Previously, we isolated a cDNA from mycorrhizal roots of Medicago truncatula that
      is predicted to encode an XTH [van Buuren, M.L., Maldonado-Mendoza, I.E., Trieu,
      A.T., Blaylock, L.A., Harrison, M.J., 1999. Novel genes induced during an
      arbuscular mycorrhizal (AM) symbiosis between M. truncatula and G. versiforme.
      Mol. Plant-Microb. Interact. 12, 171-181.]. Here, we identified the corresponding
      XTH gene, designated Mt-XTH1. The Mt-XTH1 gene contains four exons separated by
      three introns and resides on a 15-kb Xba1 fragment adjacent to a second XTH gene
      designated Mt-XTH2. Mt-XTH2 shares the same exon-intron structure as Mt-XTH1.
      Exons 2, 3 and 4 and introns 1 and 2 are identical to Mt-XTH1, while exon 1 and
      intron 3 are divergent, both in sequence and in length. Mt-XTH1 is induced
      following colonization of the roots by AM fungi but does not respond to changes
      in phosphate status. Analysis of transgenic roots expressing an Mt-XTH1
      promoterColon, two colonsuidA fusion revealed that the Mt-XTH1 promoter directs
      expression in cells throughout the root system with significantly higher levels
      of activity in mycorrhizal roots. Mt-XTH1 expression is elevated not only in the
      regions of the roots colonized by the fungus, but also at sites distal to the
      infected regions. These expression patterns are consistent with activation in
      response to a systemic signal.

PMID- 15716120
TI  - Comparative evolutionary analysis of olfactory receptor gene clusters between
      humans and mice.
AB  - Olfactory receptor (OR) genes form the largest multigene family in mammalian
      genomes. Humans have approximately 800 OR genes, but >50% of them are
      pseudogenes. By contrast, mice have approximately 1400 OR genes and pseudogenes
      are approximately 25%. To understand the evolutionary processes that shaped the
      difference of OR gene families between humans and mice, we studied the genomic
      locations of all human and mouse OR genes and conducted a detailed phylogenetic
      analysis using functional genes and pseudogenes. We identified 40 phylogenetic
      clades with high bootstrap supports, most of which contain both human and mouse
      genes. Interestingly, a particular clade contains approximately 100 pseudogenes
      in humans, whereas the numbers of pseudogenes are <20 for most of the mouse
      clades. We also found that the organization of OR genomic clusters is well
      conserved between humans and mice in many chromosomal locations. Despite the
      difference in the numbers of genes, the numbers of large genomic clusters are
      nearly the same for humans and mice. These observations suggest that the greater
      OR gene repertoire in mice has been generated mainly by tandem gene duplication
      within each genomic cluster.

PMID- 15716121
TI  - Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice variant.
AB  - Extracellular regulated kinase 5 (ERK5) is an unusually large member of the MAP
      kinase family of signaling molecules that plays an important role in cellular
      proliferation, differentiation and survival. Recently, three transcriptional
      variants of murine Erk5 were described (mErk5-a, -b and -c) that result from
      alternate splicing across introns 1 and/or 2, the net effect of which is
      translation of a peptide that lacks the kinase domain. It has been demonstrated
      that expression of mErk5-b and -c impinge on the function of the full length
      mErk5 protein product via a dominant negative effect. Here, we report the
      identification of another murine Erk5 splice variant and the orthologous human
      transcript that arise due to alternate splicing of intron 4. Failure to splice
      out intron 4 introduces a premature in-frame stop codon that directs translation
      of a peptide lacking the nuclear localization signal (NLS) and proline-rich
      region (PR). Experimental characterization demonstrated that like mERK5, mERK5-T
      becomes phosphorylated by co-expression with a constitutively active mMEK5
      (mMEK5DD), and is able to coimmunoprecipitate with both itself and mERK5. Unlike
      mERK5, however, activated ERK5-T is unable to translocate from the cytoplasm to
      the nucleus in HeLaS3 cells, causing the retention of active mERK5 in the
      cytoplasm. Taken together with previous reports of domain content modification of
      ERK5 via alternate splicing, these observations add to the suggestion that
      regulation of ERK5 signaling may be mediated, at least in part, at the level of
      RNA processing.

PMID- 15716122
TI  - Pretreatment with muscarinic receptor agonist activates a calcium-inhibitable
      adenylate cyclase in GH3 pituitary cells.
AB  - We have demonstrated previously that pretreatment of GH3 pituitary cells with
      muscarinic agonists may induce a higher cAMP formation in response to vasoactive
      intestinal peptide (VIP) or forskolin. In the present study, we further examined
      the adenylate cyclase (AC) that may be involved. We found that carbachol
      pretreatment enhanced both VIP- and forskolin-activated AC activities. The
      addition of calcium ions to the incubation buffer diminished this enhancing
      effect. Carbachol was found to induce a decrease in intracellular calcium
      concentration [Ca2+]i by inhibiting calcium influx through L-type Ca2+ channels.
      However, the incubation of cells in Ca(2+)-free buffer or in the presence of L
      type Ca2+ channel blockers had no influence on forskolin-stimulated cAMP
      formation, although both treatments induced decreases in [Ca2+]i as carbachol
      did. On the other hand, incubation in the presence of LaCl3 at a low
      concentration not being able to enter cells, forskolin-stimulated cAMP formation
      as well as the enhancing effect of carbachol-pretreatment on this response, were
      both suppressed. Similar phenomena were observed when membrane-bound AC
      activities were measured in the presence of LaCl3. Taken together, these results
      seem to suggest that pretreatment of GH3 cells with muscarinic receptor agonist
      may activate a Ca(2+)-inhibitable AC for a higher stimulated response. Low
      intracellular calcium concentrations are essential but not sufficient for this
      effect.

PMID- 15716123
TI  - Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in
      non-phagocytic cells.
AB  - Apocynin is a naturally occurring methoxy-substituted catechol, experimentally
      used as an inhibitor of NADPH oxidase. Since it acts as a potent inhibitor in
      studies with neutrophils and macrophages, no inhibitory effect can often be found
      in non-phagocyte cells. In our experiments, apocynin even stimulated reactive
      oxygen species (ROS) production by vascular fibroblasts. Even when added to
      macrophages, apocynin initially caused an increase in ROS production. The
      inhibition of ROS formation followed, suggesting that in the presence of
      leukocyte myeloperoxidase and hydrogen peroxide, apocynin is converted to another
      compound. Apocynin pre-activated with H2O2 and horseradish peroxidase (HRP)
      inhibited ROS production immediately. In non-phagocytes, apocynin stimulated ROS
      production and no inhibition was observed even after 60 min. Apocynin treated
      with H2O2 and HRP, however, decreased ROS production in the same manner as in
      macrophages. The stimulatory effect on ROS production can be abolished by tiron
      and superoxide dismutase (SOD), suggesting that superoxide was the produced
      species. The effect of apocynin was inhibited by diphenylene iodinium (DPI), a
      non-scavenging NADPH oxidase inhibitor. It can be summarized that apocynin
      stimulates cell superoxide production. In the presence of peroxidase and hydrogen
      peroxide, however, it is converted into another compound that acts as an
      inhibitor of superoxide production. It strongly suggests that under conditions in
      vivo, apocynin can have opposite effects on phagocytes and non-phagocyte cells.
      It acts as an inhibitor of phagocyte NADPH oxidase but also as a ROS production
      stimulator in non-phagocyte cells.

PMID- 15716124
TI  - Binding of hypocrellin B to human serum albumin and photo-induced interactions.
AB  - Molecular binding of hypocrellins to human serum albumin (HSA) needs to be
      further clarified considering the phototherapeutic potentials of hypocrellins to
      vascular diseases. In the current work, it was estimated that the binding
      constant of hypocrellin B (HB) to HSA was 2.28 x 10(4) M(-1). Furthermore, based
      on the fluorescence responses for both HB and the tryptophan of HSA, it was
      suggested that the binding of HB to HSA should be more specific rather than
      distributed randomly on the surface of HSA, which was also confirmed by
      photobleaching of the tryptophan via photosensitization of HB. Besides, it was
      found that both of the photo-bleaching of the tryptophan and the photo-oxidation
      of HB were principally oxygen-dependent, suggesting reactive oxygen species
      generated via the photosensitization of HB, instead of the free radicals of the
      photosensitizer (HB*-), play the most important role in photodynamic processes.

PMID- 15716125
TI  - Induction of synthesis of a large heparan sulfate proteoglycan, perlecan, by
      thrombin in cultured human coronary smooth muscle cells.
AB  - The accumulation of extracellular matrix components such as proteoglycans is a
      hallmark of an atherosclerotic lesion. A large heparan sulfate proteoglycan,
      perlecan, dramatically increases in the advanced lesion, and vascular smooth
      muscle cells are the cell type responsible for the accumulation. In this study,
      we investigated the effects of thrombin on the proteoglycan synthesis in cultured
      human coronary smooth muscle cells to determine the interrelationship between the
      accumulation of proteoglycans and the procoagulant state of blood in
      atherosclerosis. The cells were metabolically labeled with [(35)S]sulfate or
      (35)S-labeled amino acids in the presence of thrombin, and the labeled
      proteoglycans were characterized by Sepharose CL-4B molecular sieve
      chromatography and DEAE-Sephacel ion-exchange chromatography. The
      glycosaminoglycan M(r) and composition were analyzed by Sepharose CL-6B
      chromatography, and the core protein M(r) was determined by SDS-polyacrylamide
      gel electrophoresis before and after digestion with chondroitinase ABC or papain.
      The results indicate that thrombin increases the cell layer-associated heparan
      sulfate proteoglycan with a core protein size of approximately 400 kDa without
      any change in the length of the glycosaminoglycan chains when the cell density is
      high. The heparan sulfate proteoglycan was identified as perlecan by Western blot
      analysis. In addition, quantitative reverse transcription-polymerase chain
      reaction showed that thrombin elevated the steady-state level of perlecan mRNA
      but not that of versican, decorin, and syndecan-1 mRNAs, although that of
      biglycan mRNA was moderately elevated. Furthermore, the percentage of
      disaccharide units that compose perlecan heparan sulfate chains remained
      unaffected by thrombin. Therefore, it is suggested that thrombin induces the
      perlecan core protein synthesis without influencing the formation of the heparan
      sulfate chains in human coronary smooth muscle cells at a high cell density. The
      regulation of proteoglycan synthesis by thrombin may be involved in the
      accumulation of perlecan in advanced lesions of atherosclerosis.

PMID- 15716126
TI  - Evaluation of MUC6 mucin tandem repeats.
AB  - The MUC6 mucin was originally isolated from stomach mucus and is one of the major
      secreted mucins of the digestive tract. A full-length cDNA has not been isolated
      for this large molecule (greater than 15 kb) and it remains poorly studied. To
      circumvent the lack of reagents for investigating MUC6, we isolated a cDNA clone
      from a human fetal pancreatic duct cDNA library that encodes 282 amino acids of
      the MUC6 tandem repeat. A blast search with the sequence of this cDNA clone
      showed 90% homology with the original MUC6 (L07517) derived from a human stomach
      cDNA library and 95% homology both with AK096772, a MUC6-related protein isolated
      from a human prostate cDNA library and the human genome project clone AC083984.
      The MUC6 partial cDNA clone isolated from fetal pancreas was inserted into an
      epitope-tagged MUC1 mucin molecule in place of the native tandem repeat. This
      chimeric mucin was expressed in human pancreatic (Panc1) and colon (Caco2)
      carcinoma cell lines and purified for analysis of O-glycosylation by fast atom
      bombardment mass spectrometry (FAB-MS). The FAB-MS spectra showed O-glycans that
      had been detected previously on chimeric mucins carrying different tandem
      repeats, though the spectra for MUC1F/6TR mucins expressed in the Panc1 and Caco2
      cells were very different. There was a paucity of O-glycosylation in Panc1 cells
      in comparison to Caco2 cells where many more structures were evident, and the
      most abundant glycans in Panc1 cells were sialylated.

PMID- 15716127
TI  - Enzymatic synthesis of poly-N-acetyllactosamines as potential substrates for endo
      beta-galactosidase-catalyzed hydrolytic and transglycosylation reactions.
AB  - Enzymatic synthesis of GlcNAc-terminated poly-N-acetyllactosamine beta-glycosides
      GlcNAcbeta1,3(Galbeta1,4GlcNAcbeta1,3)(n)Galbeta1,4GlcNAcbeta-pNP (n=1-4) was
      demonstrated using a transglycosylation reaction of Escherichia freundii endo
      beta-galactosidase. The enzyme catalyzed a transglycosylation reaction on
      GlcNAcbeta1,3Galbeta1,4GlcNAcbeta-pNP (1), which served both as a donor and an
      acceptor, and converted 1 into p-nitrophenyl beta-glycosides
      GlcNAcbeta1,3(Galbeta1,4GlcNAcbeta1,3)(1)Galbeta1,4GlcNAcbeta-pNP (2),
      GlcNAcbeta1,3(Galbeta1,4GlcNAcbeta1,3)(2)Galbeta1,4GlcNAcbeta-pNP (3),
      GlcNAcbeta1,3(Galbeta1,4GlcNAcbeta1,3)(3)Galbeta1,4GlcNAcbeta-pNP (4) and
      GlcNAcbeta1,3(Galbeta1,4GlcNAcbeta1,3)(4)Galbeta1,4GlcNAcbeta-pNP (5). When 2 was
      used as an initial substrate, it led to the preferential synthesis of
      nonasaccharide beta-glycoside 4 to heptasaccharide beta-glycoside 3. This
      suggests that 4 is directly synthesized by transferring the tetrasaccharide unit
      GlcNAcbeta1,3Galbeta1,4GlcNAcbeta1,3Gal to nonreducing end GlcNAc residue of 2
      itself. The efficiency of production of poly-N-acetyllactosamines by E. freundii
      endo-beta-galactosidase was significantly enhanced by the addition of BSA and by
      a low-temperature condition. Resulting 2 and 3 were shown to be useful for
      studying endo-beta-galactosidase-catalyzed hydrolytic and transglycosylation
      reactions.

PMID- 15716128
TI  - Formation of an oxo-radical of peroxovanadate during reduction of
      diperoxovanadate with vanadyl sulfate or ferrous sulfate.
AB  - Formation of oxygen radicals during reduction of H(2)O(2) or diperoxovanadate
      with vanadyl sulfate or ferrous sulfate was indicated by the 1:2:2:1 electron
      spin resonance (ESR) signals of the DMPO adduct typical of standard ()OH radical.
      Signals derived from diperoxovanadate remained unchanged in the presence of
      ethanol in contrast to those from H(2)O(2). This gave the clue that they
      represent a different radical, possibly (*)OV(O(2))(2+), formed on breaking a
      peroxo-bridge of diperoxovanadate complex. The above reaction mixtures evolved
      dioxygen or, when NADH was present, oxidized it rapidly which was accompanied by
      consumption of dioxygen. Operation of a cycle of peroxovanadates including this
      new radical is suggested to explain these redox activities both with vanadyl and
      ferrous sulfates. It can be triggered by ferrous ions released from cellular
      stores in the presence of catalytic amounts of peroxovanadates.

PMID- 15716129
TI  - Rat Sertoli cells express epithelial but also mesenchymal genes after
      immortalization with SV40.
AB  - A new immortal Sertoli cell line from pubertal rat testis was established and
      characterized. We have generated the clonal line SCIT-C8 expressing established
      markers for Sertoli cells (SC) like transferrin, clusterin and steel factor/stem
      cell factor (SCF). Additionally, the immortalized cells express afadin, a protein
      which is a member of tight and adherens junctions, therefore the cells may be
      useful for studies of the blood-testis barrier (BTB) in vitro. In contrast to
      primary SC, the immortalized cells lost expression of androgen receptor and
      responsiveness to androgens and follicle-stimulating hormone. Surprisingly, we
      found mRNA expression and protein secretion of the mesenchymal markers,
      fibronectin and entactin-1, which we also observed for the immortalized SC lines,
      ASC-17D and 93RS2. In comparison to primary SC, the immortalized cells
      demonstrated enhanced adhesion in vitro. This correlated with the expression of
      entactin-1 because adhesion was strongly reduced by antibody perturbation
      experiments. Additionally, we found the alternatively spliced and primarily
      muscle cell-specific long variant of TGF-beta2 not only in peritubular cells
      (PC), but also in the primary and immortalized SC. Furthermore, all immortalized
      cell lines secreted higher amounts of TGF-beta2 than primary SC. In conclusion,
      the immortalized SC lines from different developmental stages showed a similar
      pattern of epithelial and mesenchymal markers.

PMID- 15716130
TI  - Enhanced catalytic and conformational stability of Atlantic cod trypsin upon
      neoglycosylation.
AB  - The applicability of psychrophilic enzymes is limited because of their lower
      thermodynamic stability in spite of their higher catalytic rate. In this study,
      we have shown that the thermodynamic stability of the psychrophilic Atlantic cod
      trypsin could be enhanced appreciably by covalent chemical modification with
      oxidized sucrose polymer without affecting its hydrolytic activity. The acquired
      stability of cod trypsin was found to be on par with the mesophilic porcine
      trypsin.

PMID- 15716132
TI  - Vitamin B6 compounds prevent the death of yeast cells due to menadione, a
      reactive oxygen generator.
AB  - The antioxidant effects of natural vitamin B(6) compounds on Schizosaccharomyces
      pombe cells treated with menadione sodium bisulfite (water-soluble menadione and
      a generator of superoxide, MSB) and the mechanism underlying the function were
      examined with the yeast cells treated with pyridoxal 5'-phosphate. Vitamin B(6)
      compounds showed no ex vivo reactivity toward MBS at pH 5.5 or 7.0. The yeast
      cells showed no growth in the medium containing 1.0 mM MSB. The coexistence of
      1.0 mM of each vitamin B(6) compound supported the growth of the yeast cells. The
      efficacy order was pyridoxal 5'-phosphate>/=pyridoxamine 5'
      phosphate>pyridoxamine>pyridoxal>/=pyridoxine. The first three compounds showed
      higher antioxidant activity than vitamin C did. Pyridoxal 5'-phosphate prevented
      the reduction of the glutathione content in the MSB-treated cells and, in turn,
      suppressed the increases in peroxide and thiobarbituric acid reactive substances
      in the yeast cells and increased the viability of the yeast cells under oxidative
      stress. The antioxidant function of pyridoxal 5'-phosphate was not dependent on
      the phosphorelay pathway, which finally triggers the expression of the catalase
      gene.

PMID- 15716131
TI  - Antioxidant activities of agaro-oligosaccharides with different degrees of
      polymerization in cell-based system.
AB  - The aim of the present study was to evaluate the antioxidant activity of agaro
      oligosaccharides with different degrees of polymerizations (DPs) and establish a
      relationship between the activity and DPs. The attenuate effect of
      oligosaccharides on 1,1-diphenyl-2-picryl-hydrazyl (DPPH(*)) was initially
      assessed, and the result indicated that agarohexaose showed the highest
      scavenging DPPH(*) capability (IC(50)=1.85 mg/ml). Following that, the
      intracellular antioxidant ability of agaro-oligosacharides was investigated by
      using the dichlorofluorescein (DCF) assay in human liver cell L-02 system.
      Different levels of antioxidant activities of agaro-oligosaccharides with various
      DPs were observed, and their scavenging reactive oxygen species (ROS) capability
      was associated with the improvement of the cell viability. In these
      oligosaccharides, agarohexaose possessed the highest scavenging capability, which
      could reduce 50% of oxidants generated by H(2)O(2) at 1 mg/ml. Furthermore, the
      antioxidant effect of agarohexaose on the indirect oxidation of cells induced by
      antimycin A (AA) was also tested. The results showed that agarohexaose could
      scavenge ROS generated by electron leakage and protect cells against apoptosis
      induced by ROS. It is concluded that agaro-oligosaccharides are generally
      considered as novel antioxidants which could protect cell damage caused by
      reactive oxygen species, especially agarohexaose exhibiting most desirable
      effects.

PMID- 15716133
TI  - The binding of copper ions to glycine-rich proteins (GRPs) from Cicer arietinum.
AB  - Cicer arietinum GRP1 and GRP2 are rich in glycine interposed with histidine and
      tyrosine. In order to study whether or not these proteins bind Cu(2+), circular
      dichroism (CD) and nuclear magnetic resonance (NMR) were measured for three
      synthetic peptides corresponding to sections of the protein's sequences including
      1, N(1)Y(2)G(3)H(4)G(5)G(6)G(7)N(8)Y(9)G(10)N(11), where all peptides were
      chemically blocked with an acetyl group at the N-terminus and an -NH(2) group at
      the C-terminus. The visible CD spectra for 1 showed a positive peak near 590 nm
      not at pH 6.0 but pH 7.4 in the presence of copper ions. The Cu(2+) binding
      induced a drastic change in the far-UV CD spectra, showing the occurrence of
      large conformation changes. In the 2D TOCSY NMR spectra at pH 7.4, the addition
      of small amounts of CuSO(4) caused a significant broadening of proton resonances
      of not only His4 but also Gly5, Asn8 and Asn11. CD titration experiment suggested
      that NYGHGGGNYGN including one repeat unit comprises the fundamental Cu(2+)
      binding unit.

PMID- 15716134
TI  - Merocyanine 540-sensitized photokilling of leukemia cells: role of post
      irradiation chain peroxidation of plasma membrane lipids as revealed by nitric
      oxide protection.
AB  - The lipophilic dye merocyanine 540 (MC540) localizes primarily in the plasma
      membrane (PM) of tumor cells, where it can sensitize lethal photoperoxidative
      damage of potential therapeutic importance. We postulated (i) that chain
      peroxidation triggered by iron-catalyzed turnover of nascent hydroperoxides
      (LOOHs) generated by singlet oxygen ((1)O(2)) attack on PM lipids contributes
      significantly to overall cytolethality, and (ii) that nitric oxide (NO), a known
      scavenger of organic free radicals, would suppress this and, thus, act
      cytoprotectively. In accordance, irradiation of MC540-sensitized L1210 cells
      produced 5alpha-OOH, a definitive (1)O(2) adduct of PM cholesterol, which decayed
      during subsequent dark incubation with appearance of other signature peroxides,
      viz. free-radical-derived 7alpha/beta-OOH. Whereas chemical donor (SPNO or SNAP)
      derived NO had little or no effect on post-irradiation 5alpha-OOH disappearance,
      it dose-dependently inhibited 7alpha/beta-OOH accumulation, consistent with
      interception of chain-carrying radicals arising from one-electron reduction of
      primary LOOHs. Using [(14)C]cholesterol as an L1210 PM probe, we detected
      additional after-light products of chain peroxidation, including diols (7alpha
      OH, 7beta-OH) and 5,6-epoxides, the yields of which were enhanced by iron
      supplementation, but strongly suppressed by NO. Correspondingly, photoinitiated
      cell killing was significantly inhibited by NO introduced either immediately
      before or after light exposure. These findings indicate that prooxidant LOOH
      turnover plays an important role in photokilling and that NO, by intercepting
      propagating radicals, can significantly enhance cellular resistance.

PMID- 15716135
TI  - The effect of sub-lethal ALA-PDT on the cytoskeleton and adhesion of cultured
      human cancer cells.
AB  - 5-Aminolevulinic acid (ALA), a precursor of the endogenous photosensitizer
      protoporphyrin IX, is used in the photodynamic therapy (PDT) of cancer. Sub
      lethal ALA-PDT (1-min irradiation with 370-450 nm blue light, 0.6 mW/cm(2) after
      2-h incubation with 1 mM ALA) has been earlier shown to change cell morphology
      and to inhibit both trypsin-induced detachment of cultured cancer cells from the
      plastic substrata and cell attachment to the bottom of the plastic well plates.
      In the present study, we found that such treatment of human adenocarcinoma WiDr
      cells grown in dense colonies stimulated the formation of actin cortex between
      cells in the colonies and increased the number of actin stress fibres in some,
      but not in all, cells. However, ALA-PDT did not change the microtubular
      cytoskeleton in these cells. A similar treatment of glioblastoma D54Mg cells,
      which grow separately and communicate by protrusions, caused loss of fibrillar
      actin structures in growth cones, retraction of protrusions, and surface blebbing
      in some cells. The application of the cytoskeleton inhibitors cytochalasin D,
      colchicine or taxol showed that the inhibition of trypsin-induced detachment of
      photosensitized WiDr cells was related to ALA-PDT-induced changes in actin and
      microtubular cytoskeleton. Some signal transduction processes are suggested to be
      involved in ALA-PDT-induced changes in cytoskeleton, cell shape, and adhesion.

PMID- 15716136
TI  - Purification and cDNA cloning of luxuriosin, a novel antibacterial peptide with
      Kunitz domain from the longicorn beetle, Acalolepta luxuriosa.
AB  - We have purified a novel antibacterial peptide from the hemolymph of the
      coleopteran insect Acalolepta luxuriosa, of the family Cerambyocidae, and named
      it luxuriosin. This peptide showed growth-inhibitory activity against Micrococcus
      luteus and germination- and/or growth-inhibitory activity against the conidia
      from rice blast fungus, Magnaporthe grisea. The amino acid sequence determined by
      cDNA cloning identified luxuriosin as a peptide of 88 amino acids with a
      theoretical molecular weight of 10,368.34, containing a Kunitz domain.

PMID- 15716137
TI  - Differential influence of bacitracin on plant proteolytic enzyme activities.
AB  - The effect of bacitracin on the activity of proteases extracted from pollen and
      sprouts of various plant species and compared to five commercially available
      proteases was studied. Bacitracin stimulates some pollen proteolytic enzyme
      activities, contrary to its inhibitory influence on proteases from the other
      sources. Proteases from maize pollen, inhibited by pepstatin and
      phenylmethylsulfonyl fluoride, immediately accelerate their activities after
      addition of bacitracin to the reaction mixture. The stimulating influence of
      peptide antibiotic on pollen proteases of some plants is unexpected and molecular
      mechanism of this phenomenon requires a further elucidation. The augmentation of
      allergenic response caused by pollen enzymes and drugs containing bacitracin is
      discussed.

PMID- 15716138
TI  - The YrdC protein--a putative ribosome maturation factor.
AB  - Release factor one (RF1) terminates protein synthesis in response to stop codons
      UAG and UAA. A mutant allele of RF1 causes temperature sensitive growth at 42
      degrees C. We have earlier described the isolation of a suppressor of the
      temperature sensitive phenotype. The suppressor mutation is a small deletion in
      the open reading frame yrdC, and we have shown that the DeltayrdC mutation leads
      to immature 30S subunits and, as a consequence, to fewer translating ribosomes.
      YrdC is a small conserved protein with a dsRNA-binding surface. Here, we have
      characterized the YrdC protein. We show that the deletion leads to no production
      of functional protein, and we have indications that the YrdC protein might be
      essential in a wild type background. The protein is needed for the maturation of
      16S rRNA, even though it does not interact tightly with either of the ribosomal
      subunits, or the 70S particles. The less effective maturation of rRNA affects the
      ribosomal feedback control, leading to an increase in expression from P1rrnB. We
      suggest that the function of the YrdC protein is to keep an rRNA structure needed
      for proper processing of 16S rRNA, especially at lower temperatures. This
      activity may require other factor(s). We suggest the gene be renamed rimN, and
      the mutant allele rimN141.

PMID- 15716139
TI  - Medial temporal lobe structures are needed to re-experience remote
      autobiographical memories: evidence from H.M. and W.R.
AB  - The nature and extent of retrograde amnesia in patients with medial temporal lobe
      (MTL) lesions is currently under debate. While some investigators propose a
      temporally limited role for the MTL in episodic and semantic memory, others claim
      that MTL structures are needed for episodic memories of one's entire lifetime,
      and that only semantic memory becomes independent of the MTL. To address this
      issue, we tested two amnesic patients, H.M. and W.R., with bilateral MTL lesions
      on a series of remote memory tests that together distinguished episodic memory
      from semantic memory performance. Notably, we used a new method to assess
      autobiographical memory that measured the degree of re-experiencing of personal
      happenings from the past. Both patients showed relatively spared semantic memory,
      but severe impairment on measures of autobiographical memory, with no temporal
      gradient. Our data support the view that MTL structures play a significant role
      in recalling specific personal episodes, not only from the recent past but from
      the distant past as well.

PMID- 15716140
TI  - Trunk use and co-contraction in cerebral palsy as regulatory mechanisms for
      accuracy control.
AB  - In the present study, we examined whether individuals with cerebral palsy (CP)
      systematically vary motion of the trunk and co-contraction in the upper limb as a
      function of accuracy demands. Four participants with spastic tetraparesis, four
      with spastic hemiparesis, and four healthy controls were asked to repeatedly move
      a spoon back-and-forth between two target locations. The task was externally
      paced. In half the trials the accuracy demands were increased by filling the
      spoon with water. In addition, a condition in which the trunk was fixated was
      examined. When the movements were controlled for speed, trunk motion hardly
      varied as a function of accuracy. Co-contraction in the shoulder, however, was
      systematically higher under high-accuracy demands. Trunk fixation yielded
      differential group effects on the co-contraction of the shoulder muscles. It
      increased in control participants, tended to decrease in hemiparetic
      participants, and was unaffected in tetraparetic participants. Collectively, the
      present findings show that the increased trunk involvement and high co
      contraction levels in CP should not exclusively be regarded as disorder-related
      phenomena. Regulation of co-contraction in the shoulder is a general strategy to
      cope with variations in movement-accuracy constraints, while increased trunk
      involvement proves a secondary reaction to these constraints.

PMID- 15716141
TI  - Spatial attention modulates activity in a posterior "where" auditory pathway.
AB  - Selectively listening to a single location in space modulates both the behavioral
      and electrophysiological responses to auditory stimuli presented at that
      location. Transient attention oriented in cue-target or target-target paradigms
      results in several modulations of the auditory event-related potential known as
      the Nd1, Nd2, and Nd3. By employing electrical source analysis we tested the
      hypothesis that the earliest component (the Nd1) reflects modulation of neurons
      in parietal rather than auditory cortex. It was found that the most likely
      sources of the Nd1 modulation were posterior to primary auditory cortex within or
      near the temporo-parietal junction (TPJ). This location is within the putative
      auditory "where" pathway.

PMID- 15716142
TI  - Hemispheric specialization for categorical and coordinate spatial relations
      during an image generation task: evidence from children and adults.
AB  - Hemispheric specialization of categorical and coordinate image generation was
      assessed in adults, 8-year-old and 10-year-old children. In a standardized image
      generation task, participants decided whether probes, presented in a blank grid
      (categorical task) or bracketed square (coordinate task), would have appeared on
      a previously studied letter. To ensure that participants mentally generated the
      target letter, probe location was varied. "Early" probes appeared on letter
      segments that are first produced when the letter is drawn; while "late" probes
      appeared on later produced segments. Like previous adult studies, the grid task
      elicited a left hemisphere "categorical" strategy; while the bracket task elicits
      a right hemisphere "coordinate" strategy. However, contrary to previous research,
      the results reveal the significant and complex effects of probe location on
      categorical and coordinate image generation abilities. Specifically, early probes
      elicited a strong right hemisphere advantage for both tasks across all ages,
      whereas late probes produced a left hemisphere dissociation between categorical
      and coordinate processing. The left hemisphere dissociation was evident only for
      10-year-olds and adults, suggesting that younger children are not yet proficient
      in generating spatial representations.

PMID- 15716143
TI  - A psychophysical study of visual extinction: ipsilesional distractor interference
      with contralesional orientation thresholds in visual hemineglect patients.
AB  - Visual extinction was investigated in left (n=15) and right (n=25) brain-damaged
      patients with or without visual neglect, and in normal control subjects (n=14),
      using a psychophysical paradigm. Orientation discrimination thresholds were
      determined for both left and right hemifield gratings presented either in
      isolation or simultaneously with a contralateral distractor grating. To minimize
      the influence of possible sensory-perceptual deficits, the luminances of both
      target and distractor gratings were chosen to be 20 times the luminances
      necessary to discriminate between horizontal and vertical grating orientations.
      The location of the target grating was always cued, making the distractor grating
      task irrelevant. Even after equalizing the visibility of left and right hemifield
      stimuli, neglect patients still displayed an increased interference effect from
      an ipsilesional distractor (and no interference from a contralesional
      distractor). Left or right brain-damaged controls did not show this asymmetric
      interference of irrelevant distractors, even the patients who demonstrated
      extinction on standard extinction testing. This suggests that visual extinction
      is a critical component of the visual neglect syndrome and that it involves an
      attentional deficit.

PMID- 15716144
TI  - The relationship of visual extinction to luminance-contrast imbalances between
      left and right hemifield stimuli.
AB  - Visual extinction was investigated in six right brain-damaged patients with left
      visual neglect, using a psychophysical paradigm. Orientation discrimination
      thresholds were determined for both left and right hemifield gratings presented
      either in isolation or simultaneously with a contralateral distractor grating. To
      minimize the influence of possible sensory-perceptual deficits, the luminances of
      both target and distractor gratings were chosen to be 20 times the luminances
      necessary to discriminate between horizontal and vertical grating orientations.
      When the visibility of target and distractor gratings was subjectively equalized
      in this way, neglect patients still showed a significant extinction effect, i.e.
      a significant interference of the right hemifield distractor with left hemifield
      orientation sensitivity. By manipulating the luminances of left and right
      hemifield gratings during bilateral simultaneous stimulus presentation, we
      demonstrated the role of luminance-contrast imbalances in eliciting visual
      extinction. Both decreasing the right distractor luminance and increasing the
      left target stimulus luminance resulted in an elimination of the observed
      extinction effects. These results show that not the absolute salience of one of
      two simultaneously presented stimuli, but the relative salience of both stimuli,
      is the crucial factor for inducing extinction.

PMID- 15716145
TI  - Effect of aging on stimulus-reward association learning.
AB  - The flexible learning of stimulus-reward associations when required by
      situational context is essential for everyday behavior. Older adults experience a
      progressive decline in several cognitive functions and show deficiencies in
      neuropsychological tasks requiring flexible adaptation to external feedback,
      which could be related to impairments in reward association learning. To study
      the effect of aging on stimulus-reward association learning 20 young and 20 older
      adults performed a probabilistic object reversal task (pORT) along with a battery
      of tests assessing executive functions and general intellectual abilities. The
      pORT requires learning and reversing associations between actions and their
      outcomes. Older participants collected fewer points, needed more trials to reach
      the learning criterion, and completed less blocks successfully compared to young
      adults. This difference remained statistically significant after correcting for
      the age effect of other tests assessing executive functions. This suggests that
      there is an age-related difference in reward association learning as measured
      using the pORT, which is not closely related to other executive functions with
      respect to the age effect. In human aging, structural alterations of reward
      detecting structures and functional changes of the dopaminergic as well as the
      serotonergic system might contribute to the deficit in reward association
      learning observed in this study.

PMID- 15716146
TI  - Infant holding biases and their relations to hemispheric specializations for
      perceiving facial emotions.
AB  - Since Salk [Salk, L. (1960). The effects of the normal heartbeat sound on the
      behavior of the new-born infant: implications for mental health. World Mental
      Health 12, 168-175] reported a left-side preference for cradling an infant,
      several studies have attempted to elucidate the origin of this bias. Sex and
      handedness were the first variables tested but none of them is sufficient for
      explaining this bias. Manning and Chamberlain [Manning, J. T., & Chamberlain, A.
      T. (1991). Left-side cradling and brain lateralization. Ethology and
      Sociobiology, 12, 237-244] proposed that the explanation had to do with
      hemispheric specialization of emotions and suggested that the mother could better
      monitor her infant's emotional state when holding on the left side than on the
      right side. Moreover, the infant could monitor its mother's emotional state,
      since the most expressive side of mother's face (the left) is visible to the
      infant. We used two Chimeric Figures Tasks in order to assess (1) the preferred
      visual field for perceiving an emotion and (2) the most expressive side of the
      face. Holding biases were measured in a concrete situation using an infant doll.
      Our main objective was to assess the relation between the asymmetric visual
      perception and the holding direction in a large sample of university students. We
      replicated a left-holding preference (66%) in our sample and found an effect of
      participants' holding posture and a limited effect of laterality but no effect of
      sex. The most significant finding concerns the links between the preferred visual
      field and the preferred holding side. This effect was observed in the sample of
      women, in right-handers, and in the sub-group of participants with care-giving
      skills. These findings suggest a leading role for the right hemisphere for side
      of holding.

PMID- 15716147
TI  - Crossing the midline: reducing attentional deficits via interhemispheric
      interactions.
AB  - Patients with unilateral neglect and extinction show a profound lack of awareness
      of stimuli presented contralateral to their lesion. However, many processes of
      perception are intact and contralesional stimuli seem to reach a high level of
      representation, perceptual and semantic. Some of these processes can work to
      decrease the magnitude of the attentional deficit. Here, we examine two of these
      intact processes, feature detection and perceptual grouping. First, we
      demonstrate that feature detection occurs in parallel in the contralesional
      visual fields of neglect and extinction patients. Second, we attempt to
      dissociate the influence of perceptual contours across the vertical meridian from
      the presence of an object or higher-level perceptual unit (or group) that may be
      created by these contours. We find that connections across the midline affect
      attentional deficits independently of the objects they may create. This suggests
      that several effects of grouping on neglect and extinction may be mediated by
      long-range cortical interactions that arise from connections across the vertical
      meridian.

PMID- 15716148
TI  - Prose recall and amnesia: more implications for the episodic buffer.
AB  - Baddeley and Wilson [Baddeley, A. D., & Wilson, F. B. (2002). Prose recall and
      amnesia: implications for the structure of working memory. Neuropsychologia 40,
      1737-1743.] have argued that their finding of a positive association between
      amnesics' immediate prose recall scores and their scores on measures of executive
      function and fluid intelligence supports the view that an episodic buffer exists.
      However, the pattern of data from amnesics tested in our laboratory presented
      some problems for this conceptualisation of the episodic buffer.

PMID- 15716149
TI  - The M170 is selective for faces, not for expertise.
AB  - Are the mechanisms for face perception selectively involved in processing faces
      per se, or do they also participate in the processing of any class of visual
      stimuli that share the same basic configuration and for which the observer has
      gained substantial visual expertise? Here we tested the effects of visual
      expertise on the face-selective "M170", a magnetoencephalography (MEG) response
      component that occurs 170 ms after stimulus onset and is involved in the
      identification of individual faces. In Experiment 1, cars did not elicit a higher
      M170 response (relative to control objects) in car experts compared to controls
      subjects. In Experiment 2, the M170 amplitude was correlated with successful face
      identification, but not with successful car identification in car experts. These
      results indicate that the early face processing mechanisms marked by the M170 are
      involved in the identification of faces in particular, not in the identification
      of any objects of expertise.

PMID- 15716150
TI  - Is judgement of line orientation selectively impaired in right brain damaged
      patients?
AB  - The judgement of line orientation test (JLOT) is widely used to assess visuo
      spatial processing. Most neuropsychological studies have shown that on this task
      right hemisphere damaged (RHD) patients are significantly more impaired than left
      hemisphere damaged (LHD) patients, suggesting a dominant role of the right
      hemisphere in discriminating line orientation. To investigate whether other
      factors can affect performance on JLOT, a modified version of the test,
      consisting of the 30 original test items and their mirror images, was employed.
      In Experiment 1 normal participants were more accurate in discriminating the left
      lines of the original items, and the right lines of the mirror-reversed items,
      thus indicating that in original JLOT the stimulus arrays comprise lines on the
      left side that are easier to judge than lines on the right. In Experiment 2, RHD
      patients with visual neglect were significantly more impaired than patients
      without neglect, who performed similarly independently from the side of the
      lesion. Among patients without neglect, however, LHD patients were more accurate
      than RHD patients without neglect with the original items, but produced more
      errors than RHD patients without neglect when faced with the mirror-reversed
      items. Overall, the results of the present study suggest that the greater
      impairment on standard JLOT shown by RHD patients has to be interpreted as the by
      product of the presence of visual neglect, which is more frequent following right
      hemisphere damage, and of the uneven distribution of the stimulus lines, which
      are easier to discriminate in the left space. The clinical and theoretical
      implications of the results are discussed.

PMID- 15716151
TI  - Retrograde amnesia: neither partial nor complete hippocampal lesions in rats
      result in preferential sparing of remote spatial memory, even after reminding.
AB  - Many lesion experiments have provided evidence that the hippocampus plays a time
      limited role in memory, consistent with the operation of a systems-level memory
      consolidation process during which lasting neocortical memory traces become
      established [see Squire, L. R., Clark, R. E., & Knowlton, B. J. (2001).
      Retrograde amnesia. Hippocampus 11, 50]. However, large lesions of the
      hippocampus at different time intervals after acquisition of a watermaze spatial
      reference memory task have consistently resulted in temporally ungraded
      retrograde amnesia [Bolhuis, J. J., Stewart, C. A., Forrest, E. M. (1994).
      Retrograde amnesia and memory reactivation in rats with ibotenate lesions to the
      hippocampus or subiculum. Quarterly Journal of Experimental Psychology 47B, 129;
      Mumby, D. G., Astur, R. S., Weisend, M. P., Sutherland, R. J. (1999). Retrograde
      amnesia and selective damage to the hippocampal formation: memory for places and
      object discriminations. Behavioural Brain Research 106, 97; Sutherland, R. J.,
      Weisend, M. P., Mumby, D., Astur, R. S., Hanlon, F. M., et al. (2001). Retrograde
      amnesia after hippocampal damage: recent vs. remote memories in two tasks.
      Hippocampus 11, 27]. It is possible that spatial memories acquired during such a
      task remain permanently dependent on the hippocampus, that chance performance may
      reflect a failure to access memory traces that are initially unexpressed but
      still present, or that graded retrograde amnesia for spatial information might
      only be observed following partial hippocampal lesions. This study examined the
      retrograde memory impairments of rats that received either partial or complete
      lesions of the hippocampus either 1-2 days, or 6 weeks after training in a
      watermaze reference memory task. Memory retention was assessed using a novel
      'reminding' procedure consisting of a series of rewarded probe trials, allowing
      the measurement of both free recall and memory reactivation. Rats with complete
      hippocampal lesions exhibited stable, temporally ungraded retrograde amnesia, and
      could not be reminded of the correct location. Partially lesioned rats could be
      reminded of a recently learned platform location, but no recovery of remote
      memory was observed. These results offer no support for hippocampus-dependent
      consolidation of allocentric spatial information, and suggest that the
      hippocampus can play a long-lasting role in spatial memory. The nature of this
      role--in the storage, retrieval, or expression of memory--is discussed.

PMID- 15716152
TI  - It takes the whole brain to make a cup of coffee: the neuropsychology of
      naturalistic actions involving technical devices.
AB  - Left hemisphere dominance has been established for use of single familiar tools
      and tool/object pairs, but everyday action in natural environment frequently
      affords multi-step actions with more or less novel technical devices. One purpose
      of our study was to find out whether left hemisphere dominance extends to such
      naturalistic action. Another aim was to analyze the cognitive components
      contributing to success or failure. Patients with LBD and aphasia, patients with
      RBD, and healthy controls were examined on experimental tests assessing retrieval
      of functional knowledge from semantic memory, inference of function from
      structure, and solution of mechanical and non-mechanical multi-step problems, and
      were confronted with two naturalistic tasks involving technical devices:
      preparing coffee with a drip coffee maker and fixing a cassette recorder. Both
      patient groups were about equally impaired on both naturalistic actions. Analysis
      of the experimental tests and their correlations to naturalistic actions
      suggested that different cognitive deficits caused failure in both patient
      groups, and that in LBD patients there were also different causes for failure on
      both naturalistic actions. The main difficulty of RBD patients seemed to reside
      in the demand to keep track of multi-step actions. In aphasic LBD patients
      difficulties with making coffee but not the cassette recorder were correlated
      with aphasia and defective retrieval of functional knowledge from semantic
      memory, whereas the cassette recorder correlated more strongly with a test
      probing solution of multi-step mechanical problems. Inference of function from
      structure which had been shown to be important for use of single familiar tools
      or tool/objects pairs [Goldenberg, G., Hagmann, S. (1998). AT Tool use and
      mechanical problem solving in apraxia. Neuropsychologia, 36, 581-589] appeared to
      play only a subordinate role for naturalistic actions involving technical
      devices.

PMID- 15716153
TI  - Lack of inhibition in Parkinson's disease: evidence from a lexical decision task.
AB  - Persons affected by Parkinson's disease (PD) often show an increased semantic
      priming effect from target words in lexical decision tasks (hyper-priming) as
      compared to age-matched controls. In this study, a lexical decision task was used
      to investigate both semantic priming (Experiment 1) and repetition priming
      (Experiment 2) from distractor words in PD patients and age-matched controls.
      With this negative priming procedure, target words in successive trials are never
      related, and therefore participants always have to switch between unrelated
      target words. Instead, it is the distractor prime word that is either related or
      unrelated to the subsequent target, giving the measure of priming. Results showed
      that PD patients demonstrated a robust effect of positive semantic priming from
      distractor words. Participants from the control group did not show any semantic
      priming effect (positive or negative) from distractors. Similarly, PD patients
      showed positive repetition priming from distractor words, but the control group
      showed significant repetition negative priming. These results support the view
      that the hyper-priming effect typically shown by persons with Parkinson's disease
      is the result of impaired inhibitory processes required to control word
      activation during reading.

PMID- 15716154
TI  - Apolipoprotein E and category fluency: evidence for reduced semantic access in
      healthy normal controls at risk for developing Alzheimer's disease.
AB  - Two groups of non-demented individuals, who differed on genetic risk for
      Alzheimer's disease (AD) based on their apolipoprotein E (APOE) genotype, were
      tested on a category fluency task. Twenty varepsilon4 carriers and twenty
      varepsilon4 non-carriers were tape recorded while saying animal names for ten
      minutes. Five measures were examined: total names generated; total clusters; mean
      cluster size; mean within-cluster retrieval time; and mean between-cluster
      retrieval time. Groups were matched on age and education and scored as normal on
      a battery of psychometric tests. The varepsilon4 carriers generated significantly
      fewer names and clusters, and took significantly longer to access clusters, when
      compared to the varepsilon4 non-carriers. No group differences were found for
      cluster size or within-cluster retrieval times. We previously reported [Rosen, V.
      M., Bergeson, J. L., Putnam, K., Harwell, A., Sunderland, T. (2002). Working
      memory and apolipoprotein E: What's the connection? Neuropsychologia 40, 2226
      2233] that the varepsilon4 carriers in the present study scored significantly
      lower than the varepsilon4 non-carriers on a measure of working
      memory/attentional capacity [Operation Span Task, see Turner, M. L., Engle, R. W.
      (1989). Is working memory capacity task dependent? Journal of Memory and Language
      28, 127-154]. In the present study, a significant negative relationship found
      between span performance and between-cluster retrieval times suggested that
      reduced attentional capacity may have negatively impacted semantic access for the
      varepsilon4 carriers. Finally, we found significant relationships between a Trail
      Making Test [Reitan, R. M. (1992). Trail Making Test, manual for administration
      and scoring. Tucson, AZ: Reitan Neuropsychology Laboratory] "switch" measure
      (Form B-Form A) and three of the five fluency measures. The findings suggested
      that the varepsilon4 carrier's reduced attentional capacity may have interfered
      with their covertly shifting attention among subcategories in the fluency task,
      resulting in fewer names and clusters generated and longer times to access
      clusters.

PMID- 15716155
TI  - Dopaminergic basis for deficits in working memory but not attentional set
      shifting in Parkinson's disease.
AB  - Although Parkinson's disease is a common neurodegenerative disorder characterised
      by its motoric symptoms, there is an increasing recognition of accompanying
      impairments in cognition that have a profound impact on the quality of life of
      these patients. These deficits predominantly affect executive function and
      impairments of working memory have been frequently reported. However, the
      underlying neurochemical and pathological basis for these deficits are not well
      understood. In this study, 20 patients were tested 'on' and 'off' levodopa (L
      dopa) medication on a task that allowed different aspects of working memory
      function such as maintenance, retrieval and manipulation to be tested within the
      same general paradigm as well as on an unrelated test of attentional set
      shifting, which is known to be sensitive to deficits in early Parkinson's
      disease. Compared to healthy volunteers, PD patients were impaired at
      manipulation more than maintenance or retrieval of information within working
      memory. The patients were also impaired at the attentional set-shifting task.
      However, whereas L-dopa ameliorated the working memory deficit in manipulation
      (improving both accuracy and cognitive response time), it had no effect on the
      attentional set-shifting impairment. These results confirm that working memory
      deficits in PD are both psychologically specific and related to dopamine
      depletion. It is anticipated that greater understanding of these mechanisms will
      lead to future therapeutic improvements.

PMID- 15716156
TI  - Differing neuropsychological and neuroanatomical correlates of abnormal reading
      in early-stage semantic dementia and dementia of the Alzheimer type.
AB  - Individuals with semantic dementia (SD) were differentiated neuropsychologically
      from individuals with dementia of the Alzheimer type (DAT) at very mild-to-mild
      stages (clinical dementia rating 0.5 or 1). A picture naming and recognition
      memory experiment provided a particularly useful probe for early identification,
      with SD individuals showing preserved picture recognition memory and impaired
      naming, and DAT individuals tending to show the reverse dissociation. The
      identification of an early SD group provided the opportunity to inform models of
      reading by exploring the influence of isolated lexical semantic impairment on
      reading regular words. Results demonstrated prolonged latency in both SD and DAT
      group reading compared to a control group but exaggerated influence of frequency
      and length only for the SD group. The SD reading pattern was associated with
      focal atrophy of the left temporal pole. These cognitive-neuroanatomical findings
      suggest a role for the left temporal pole in lexical/semantic components of
      reading and demonstrate that cortical thickness differences in the left temporal
      pole correlate with prolonged latency associated with increased reliance on
      sublexical components of reading.

PMID- 15716157
TI  - The neural origins of specific and general memory: the role of the fusiform
      cortex.
AB  - Recognition of an object can be based on memory for specific details of a prior
      encounter with the object, or on a more general memory for the type of object
      previously encountered. Responding on the basis of general information alone can
      sometimes produce memory errors involving both distortion and forgetting, but
      little is known about the neural origins of general versus specific recognition.
      We extended the standard subsequent memory paradigm to examine whether neural
      activity at encoding predicts whether an object will subsequently elicit specific
      as compared to general memory. During event-related functional magnetic resonance
      imaging (fMRI), participants viewed objects and made size judgments about them.
      Later, they viewed same, similar, and new objects, labeling each as "same,"
      "similar," or "new." Specific recognition was indicated by a "same" response to a
      same object. By contrast, general, non-specific recognition was indicated by
      either a "same" response to a similar object (false memory) or a "similar"
      response to a same object (partial memory). As predicted, specific recognition,
      as compared to non-specific recognition, was associated with encoding-related
      activity in the right fusiform cortex, while non-specific recognition, as
      compared to forgetting, was associated with encoding-related activity in the left
      fusiform cortex. Furthermore, all successful recognition (specific and general),
      as compared to forgetting, was associated with encoding-related activity in
      bilateral fusiform cortex. These results suggest that the right fusiform cortex
      is associated with specific feature encoding, while the left fusiform cortex is
      involved in more general object encoding.

PMID- 15716158
TI  - Metacognition and false recognition in patients with frontal lobe lesions: the
      distinctiveness heuristic.
AB  - The distinctiveness heuristic is a response mode in which participants expect to
      remember vivid details of an experience and make recognition decisions based on
      this metacognitive expectation. Whereas much is known about the cognitive
      processes that are involved in using the distinctiveness heuristic, little is
      known about the corresponding brain processes. Because such metacognitive
      processes that involve the evaluation and control of one's memory are believed to
      be dependent upon the frontal lobes, the authors examined whether the
      distinctiveness heuristic could be engaged to reduce false recognition in a
      repetition lag paradigm in patients with lesions of their frontal lobes. Half of
      the participants studied pictures and corresponding auditory words; the other
      half studied visual and auditory words. Studied and novel items were presented at
      test as words only, with all novel items repeating after varying lags. Controls
      who studied pictures were able to reduce their false recognition of repeated lag
      items relative to those controls who studied words, demonstrating their use of
      the distinctiveness heuristic. Patients with frontal lobe lesions showed similar
      levels of false recognition regardless of whether they studied pictures and words
      or words only, suggesting that they were unable to use the distinctiveness
      heuristic. The authors suggest that the distinctiveness heuristic is a
      metacognitive strategy, dependent upon the frontal lobes, that may be engaged by
      healthy individuals to reduce their false recognition.

PMID- 15716159
TI  - Kanizsa subjective figures capture visual spatial attention: evidence from
      electrophysiological and behavioral data.
AB  - Figural binding and attention are two important processes that help to perceive
      the outside world. Binding is necessary to link together the different features
      of single objects which are represented in a distributed fashion in the brain.
      Attention serves to focus onto a small subset of incoming information. It is
      still not clear how exactly these two mechanisms operate and interact. We
      performed two experiments employing illusory Kanizsa figures (KFs) to investigate
      the temporal order of figural binding and spatial attention. In a visual search
      task, subjects had to detect the presence of a KF among distractor stimuli. We
      found only a slight increase of reaction times when increasing the number of
      distractors, indicating that KFs popped out and drew the perceiver's attention.
      In a further event-related potential (ERP) study, we used displays of the search
      task as non-informative cue for a subsequent target choice-reaction task.
      Enhanced contralateral negative amplitudes (starting at about 230 ms) over
      ventral occipital areas were found for cue displays which included a KF. For
      target stimuli, faster reaction times and enhanced ipsilateral N1 amplitudes over
      occipito-parietal areas were observed for validly (target presentation inside a
      KF) as compared to invalidly cued targets (target presentation outside a KF).
      Furthermore, enhanced contralateral N1 amplitudes were found for invalidly cued
      targets. It might be that interactions between perceptual closure processing of
      the ventral pathway and spatial target processing of the dorsal pathway
      contributed to the present result. We conclude that KFs automatically capture
      spatial attention when used as visual cues.

PMID- 15716161
TI  - Comprehension of humor in primary agenesis of the corpus callosum.
AB  - Individuals with agenesis of the corpus callosum (ACC) can, in some cases,
      perform normally on standardized intelligence tests. Nevertheless, recent studies
      suggest that individuals with ACC and normal IQ scores have deficits in domains
      of fluid and social intelligence. Anecdotal reports from families suggest
      diminished appreciation of the subtleties of social interactions, and deficits in
      the comprehension of jokes and stories. In this research, both the cartoon and
      narrative joke subtests of a humor test (developed by Brownell et al. [Brownell,
      H., Michel, D., Powelson, J., & Gardner, H. (1983). Surprise but not coherence:
      sensitivity to verbal humor in right-hemisphere patients. Brain and language,
      18(1), 20-27] and Bihrle et al. [Bihrle, A. M., Brownell, H. H., Powelson, J. A.,
      & Gardner, H. (1986). Comprehension of humorous and non-humorous materials by
      left and right brain-damaged patients. Brain and Cognition, 5(4), 399-411]) were
      given to 16 adults with complete ACC (all with IQs>80) and 31 controls of similar
      age and IQ. Individuals with ACC performed worse than controls on the narrative
      joke subtest (p<.025) when VIQ was controlled. However, on the cartoon subtest
      the two groups were not significantly different. Covarying age, forms of IQ,
      narrative memory, set-switching, and literal language comprehension did not
      substantially alter the group difference. However, covarying comprehension of
      nonliteral language and proverbs eliminated the difference, suggesting a common
      origin for the comprehension of jokes, nonliteral language, and proverbs, most
      likely related to capacity for understanding second-order meanings.

PMID- 15716160
TI  - The role of the temporal lobe semantic system in number knowledge: evidence from
      late-stage semantic dementia.
AB  - Previous reports have demonstrated that many aspects of number knowledge remain
      unimpaired in semantic dementia, despite severe comprehension problems in other
      domains. It is argued that this advantage for numbers arises because the disease
      spares the parietal lobe magnitude system thought to be critical for number
      processing. Models of numerical cognition that favour a separation between verbal
      and magnitude representations of number might, however, predict a restricted
      impairment of the verbal number code in this condition. We obtained support for
      this hypothesis in a patient with late-stage semantic dementia. She was impaired
      at a variety of tasks tapping the verbal number code; for example, reading and
      writing Arabic numerals, naming and word-picture matching with dot pictures,
      reading aloud number words, digit span and magnitude comparison/serial ordering
      tasks with number words. In contrast, she demonstrated good understanding of the
      magnitude and serial order of numbers when tested with Arabic numerals and non
      symbolic representations. These findings suggest that although the magnitude
      meaning of numbers is isolated from the temporal lobe semantic system, the
      anterior infero-temporal lobe may play a critical role in binding English number
      words to their non-symbolic magnitude meaning.

PMID- 15716162
TI  - Deficient internal models for planning hand-object interactions in apraxia.
AB  - Motor imagery (MI) has been associated with planning stages of motor production,
      and in particular, with internal models that predict the sensory consequences of
      motor commands and specify the motor commands required to achieve a given
      outcome. In this study we investigated several predictions derived from the
      hypothesis that ideomotor apraxia (IM), a deficit in pantomime and imitation of
      skilled actions, may be attributable in part to deficits in internal models for
      planning object-related actions, in the face of relatively intact on-line,
      feedback-driven control of action. This hypothesis predicts that in IM, motor
      imagery should be (a) strongly correlated with other motor tasks not providing
      strong visual, tactile, and proprioceptive feedback from objects, i.e., object
      related pantomime and imitation; (b) poorly correlated with performance tasks
      providing strong environmental feedback about the locations of effectors and
      targets, i.e., actual interaction with objects; and (c) particularly deficient in
      conditions that are computationally difficult for the motor planning system.
      Eight left fronto-parietal stroke patients with IM, five stroke patients without
      IM, and six healthy matched controls imagined grasping dowels and widgets
      presented at varying orientations, and actually grasped the same objects. The
      experimental predictions were confirmed. In addition, patients with IM and motor
      imagery deficits were significantly more likely than the non-apraxic group to
      have lesions in the intraparietal sulcus, a region previously implicated in
      imagery for hand-object interactions. The findings suggest a principled
      explanation for the deficits of IM patients in object-related gesture pantomime,
      imitation, and learning of new object-related gestures.

PMID- 15716163
TI  - Working memory functioning in schizophrenia patients and their first-degree
      relatives: cognitive functioning shedding light on etiology.
AB  - There is accumulating evidence for involvement of the prefrontal cortex (PFC) in
      the pathophysiology of schizophrenia. A primary function supported by the PFC is
      working memory (WM). Findings from WM studies in schizophrenia can provide
      insight into the nature of clinical symptoms and cognitive deficits associated
      with this disorder, as well as begin to suggest areas of underlying
      neuropathology. To date, studies have not adequately investigated different WM
      domains (e.g., verbal, spatial, or object) or processing requirements (e.g.,
      maintenance, monitoring, or manipulation), shown to be associated with distinct
      patterns of neural activation, in schizophrenia patients and their well
      relatives. Accordingly, this study evaluated the performance of schizophrenia
      patients, their first-degree biological relatives, and nonpsychiatric controls on
      a comprehensive battery of WM tasks and investigated the association among WM
      deficits and schizophrenia-spectrum psychopathology. The findings indicate that
      schizophrenia patients are consistently impaired on WM tasks, irrespective of WM
      domain or processing requirements. In contrast, their unaffected relatives are
      only impaired on WM tasks with higher central executive processing requirements.
      This pattern of WM performance may further implicate DLPFC dysfunction in the
      liability for schizophrenia and has implications for future cognitive, genetic,
      and neurodevelopmental research.

PMID- 15716164
TI  - Internally generated and directly cued task sets: an investigation with fMRI.
AB  - It is widely acknowledged that the prefrontal cortex (PFC) plays a major role for
      goal-directed behaviour. In this context it is usually necessary to coordinate
      environmental information and internally represented intentions. Such goal
      directed "endogenous control processes" can be investigated with the task
      switching paradigm in which participants are required to alternate between
      different tasks. In the present study, we aimed at investigating different
      degrees of endogenous control by introducing two cue types with varying
      directness of the cue-task association. The "transition cues" informed the
      participants about repeating or switching the task but not about the task
      identity. Contrary to that, the "task cues" were directly associated with the
      upcoming task set. Since the transition cues are not directly associated with the
      task set they should require a higher demand of endogenous control than the task
      cues. The comparison of both cue types revealed frontolateral as well as
      frontomedian activations for the transition cue. We assume that the frontolateral
      activation reflects the coordination of information within working memory (WM)
      and the frontomedian cortex reflects the higher demand for endogenous control.
      Furthermore, regions of interest (ROIs) analyses indicate an important role for
      anterior regions along the left inferior frontal sulcus and frontomedian wall.
      This is suggested to reflect a functional gradient in anterior-posterior
      direction which is linked to the relative degree of required endogenous control.

PMID- 15716165
TI  - Lateralised processing of positive facial emotion: sex differences in strength of
      hemispheric dominance.
AB  - Sex differences in lateralisation have been examined frequently, but have found
      varying and contradictory results. The experiment presented in this paper
      examines the lateralisation of processing positive facial emotion in 276 right
      handed undergraduates (138 males, 138 females). All participants completed two
      behavioural tests of lateralisation: a handedness preference questionnaire and a
      chimeric faces emotion judgement task, which measured strength of lateralisation
      for the perception of positive facial emotion. A highly significant difference
      was found for the chimeric faces task only: males were more strongly lateralised
      than females, although both males and females tended to be right hemisphere
      dominant. The results suggest that females are more bilaterally distributed and
      hence have greater access to mechanisms located in each hemisphere.

PMID- 15716166
TI  - Covert manual response preparation triggers attentional shifts: ERP evidence for
      the premotor theory of attention.
AB  - The premotor theory of attention claims that the preparation of goal-directed
      action and shifts of attention are closely linked, because they are controlled by
      shared sensorymotor mechanisms. Until now, support for this theory has come
      primarily from studies demonstrating links between saccade programming and
      attention shifts. The present event-related brain potential (ERP) study
      demonstrated that attentional orienting processes are also elicited during the
      covert preparation of unimanual responses. ERPs were recorded in the interval
      between a visual response-hand selection cue and a subsequent visual Go/Nogo
      signal when participants prepared to lift their left or right index finger.
      Lateralised ERP components elicited during response preparation were very similar
      to components previously observed during instructed endogenous attention shifts,
      indicating that analogous attentional orienting processes are activated in both
      cases. Somatosensory ERP components (P90, N140) were enhanced when task
      irrelevant tactile probes were delivered during response preparation to the hand
      involved in an anticipated response, even when probes were presented well in
      advance of response execution. These results suggest that attentional shifts are
      triggered during unimanual response preparation, as predicted by the premotor
      theory. This link between manual response programming and attention is consistent
      with the hypothesis that common mechanisms are involved in the control of
      attention and action.

PMID- 15716167
TI  - Event-related potentials for response inhibition in Parkinson's disease.
AB  - This study investigated inhibitory function in patients with Parkinson's disease
      (PD) by recording event-related brain potentials (ERPs) during a Go/NoGo task.
      Fourteen healthy volunteers and 13 patients with PD without dementia performed a
      cued continuous performance test that included Go and NoGo trials. The peak
      latency, amplitude, and topographic distributions of the ERPs to Go and NoGo
      stimuli were analyzed. Cognitive function was evaluated using the Wisconsin Card
      Sorting Test (WCST), Kana Pick-out Test, and Verbal Fluency Test (VFT).
      Performances in the WCST and VFT were significantly impaired in the PD group as
      compared with the control group. The PD group had significantly higher rates of
      omission and commission errors during the ERP task. The ERP study found no
      differences in the latency and amplitude of the Go-P3 between the two groups. By
      contrast, the NoGo-P3 latency was significantly longer in the PD group than in
      the control group. The amplitudes of the NoGo-P3 and NoGo-N2 were also
      significantly smaller in the PD group than in the control group. The NoGo-P3
      latency was significantly correlated with the Kana Pick-out Test and VFT scores.
      The NoGo-P3 amplitude was significantly correlated with the WCST and VFT scores,
      as well as with the number of commission errors. There were no significant
      correlations between the cognitive function tests and either the Go-P3 or NoGo-N2
      measures. The behavioral and ERP data suggest that there is selective impairment
      of inhibitory function in PD and that this deficit may be related to impaired
      inhibitory executive function in the frontal lobe.

PMID- 15716168
TI  - Covert orienting to exogenous and endogenous cues in children with spina bifida.
AB  - Children with spina bifida meningomyelocele and hydrocephalus (SBM) have
      congenital dysmorphology of the midbrain and thinning of the posterior cortex,
      brain regions associated with the control of covert orienting. We studied cued
      covert orienting in 92 children with SBM, and 40 age-matched typically developing
      controls. Cues were of three types: exogenous (luminance change in a peripheral
      box either valid or invalid for upcoming target location), endogenous arrow (a
      central arrow either valid or invalid for upcoming target location), or
      endogenous word (a central word either valid or invalid for upcoming target
      location). Compared to controls, children with SBM showed slowed covert orienting
      to both exogenous and endogenous cues and a higher cost of attentional
      disengagement (e.g., a greater cue-validity effect) for exogenous although not
      for endogenous cues. Covert orienting deficits were associated with midbrain
      dysmorphology in the form of beaking of the tectum, and with right posterior
      brain volume loss.

PMID- 15716186
TI  - Overactive bladder: a clinical entity or a marketing hype?

PMID- 15716187
TI  - The vicious cycling: bicycling related urogenital disorders.
AB  - PURPOSE: Bicycle riding is one of the most popular means of transportation,
      recreation, fitness and sports among millions of people of all ages who ride on
      road and off road, using a variety of bicycle types. It is also a readily
      available form of aerobic non-impact exercise with established cardiovascular
      beneficial effects. Bicycles are also a common source of significant injuries.
      This review focuses upon the specific bicycling related overuse injuries
      affecting the genitourinary tract. MATERIALS AND METHODS: MEDLINE search of the
      literature on bicycling and genitourinary disorders was performed using multiple
      subject headings and additional keywords. The search yielded overall 62 pertinent
      articles. We focused primarily on the most prevalent related disorders such as
      pudendal nerve entrapment, erectile dysfunction and infertility. The potential
      effect of bicycling on serum PSA level was also discussed in depth in view of its
      recognized clinical importance. Infrequent disorders, which were reported
      sporadically, were still addressed, despite their rarity, for the
      comprehensiveness of this review. RESULTS: The reported incidence of bicycling
      related urogenital symptoms varies considerably. The most common bicycling
      associated urogenital problems are nerve entrapment syndromes presenting as
      genitalia numbness, which is reported in 50-91% of the cyclists, followed by
      erectile dysfunction reported in 13-24%. Other less common symptoms include
      priapism, penile thrombosis, infertility, hematuria, torsion of spermatic cord,
      prostatitis, perineal nodular induration and elevated serum PSA, which are
      reported only sporadically. CONCLUSIONS: Urologists should be aware that
      bicycling is a potential and not an infrequent cause of a variety of urological
      and andrological disorders caused by overuse injuries affecting the genitourinary
      system.

PMID- 15716188
TI  - The probiotic approach: an alternative treatment option in urology.
AB  - OBJECTIVE: The prophylactic and therapeutic use of probiotic microorganisms is a
      wide and still controversial field. The review paper is aimed to summarize recent
      findings on the health-benefiting effects of probiotics in urological diseases.
      The use of certain beneficial strains against urogenital infections, bladder
      cancer recurrence and renal stone formation is discussed. METHODS: Literature
      search of PubMed documented publications and abstracts from meetings. RESULTS:
      Various clinical trials have now been performed which substantiate the beneficial
      effects of the probiotic strains L. rhamnosus GR-1, L. fermentum RC-14 and L.
      crispatus CTV-05 against urogenital infections, such as urinary tract infections
      and bacterial vaginosis. The potential of L. casei Shirota to reduce the
      recurrence rate of bladder cancer is one of the most intriguing examples for the
      use of probiotics in medical practice. The use of O. formigenes in the prevention
      of calcium oxalate stone disease was only recently suggested and needs to be
      further investigated. CONCLUSION: Clinical trials increasingly provide a profound
      scientific basis for the use of probiotics in medicinal practice including
      urology. Efforts to make probiotic products available which are validated
      according to the guidelines recommended by the WHO and FAO and produced according
      to Good Manufacturing Practice will contribute to the acceptance of probiotic
      therapy by both the physicians and the patients.

PMID- 15716189
TI  - Can we obtain better specimens with an end-cutting prostatic biopsy device?
AB  - OBJECTIVE: Our aim was to compare the tissue yield of two different prostate
      biopsy instruments: the newer end-cut versus standard side-notch technique.
      METHODS: A total of 87 patients, who underwent transrectal ultrasound guided
      prostate biopsy were included in the study between February 2003 and July 2003.
      Twenty-five patients underwent prostate biopsy with the end-cut technique with a
      stroke length of 33 mm (EC-33), 25 patients were biopsied with a stroke length of
      23 mm of the same instrument (EC-23) whereas the remaining 37 patients underwent
      biopsy with an instrument working with side-notch technique with a 22 mm stroke
      length (SN). The length, weight and weight/length ratio (WLR) were measured for
      each biopsy core. The pathologic specimens were evaluated qualitatively. The
      length, weight and WLR as well as the complication rates, pain, zero biopsy
      rates, pathologic quality and cancer detection rates were compared between the
      groups. RESULTS: Three groups were similar according to age, PSA values (free,
      total, free/total), prostate volumes (TZ, total) and PSA densities. The cancer
      detection rate was not statistically different between groups and was overall
      20,9%. As the groups were compared according to mean core lengths, weights and
      densities the sequence was found to be EC-33>EC-23>SN. The EC group had higher
      prostatic glandular capture rates and better pathological quality. However, the
      zero biopsy rates were 12%, 7% and 1% for EC-33, EC-23 and SN groups,
      respectively and the difference was statistically significant. The complication
      rates after biopsy were similar for each group. The mean visual analogous scale
      scores were not significantly different between the groups. Another interesting
      finding was that cores containing cancer were heavier and denser than the others
      regardless of the instrument type. CONCLUSION: The use of the presented new
      instrument, enables to obtain longer, heavier and denser cores with a higher
      pathologic quality and glandular coverage without increasing the number of
      biopsies and morbidity. However, the relatively high zero biopsy rate is a
      handicap that needs to be improved.

PMID- 15716190
TI  - Complexed prostate specific antigen density is better than the other PSA
      derivatives for detection of prostate cancer in men with total PSA between 2.5
      and 20 ng/ml: results of a prospective multicenter study.
AB  - PURPOSE: This prospective, multicenter study was initiated to evaluate the
      diagnostic performance of PSA, free/total PSA (f/tPSA) and complexed PSA (cPSA)
      with volume-based parameters for early detection of prostate cancer in patients
      with PSA between 2.5 and 20 ng/ml. MATERIALS AND METHODS: 408 subjects with serum
      PSA values between 2.5 and 20 ng/ml regardless of digital rectal examination
      (DRE) were included in to the study. The diagnostic validity, sensitivity,
      specificity and cut-off values were evaluated by Receiver Operating
      Characteristic (ROC) curve analysis. RESULTS: Of 408 patients 77 (18.9%) were
      positive for prostate cancer. Digital rectal examination was non-suspicious in
      86% (351/408) of the patients. Area under curve (AUC) values for cPSA were better
      than PSA and f/tPSA in patients with PSA values of 2.5-10 ng/ml and 4-10 ng/ml,
      as well as the whole group. Furthermore, on ROC curve analysis cPSAD was the best
      predictor of prostate cancer for all PSA ranges regardless of the DRE findings
      except PSA values between 2.5 and 4 ng/ml. The cut-off value of cPSAD at 90%
      sensitivity was 0.06 ng/ml/cm(3) with a 35.3% specificity saving 126 unnecessary
      biopsies in the whole group. CONCLUSION: cPSA might be a better initial test than
      PSA for prostate cancer detection and measurement of cPSA alone and its
      derivatives obviate the need for additional fPSA testing.

PMID- 15716191
TI  - Pretreatment serum testosterone level as a predictive factor of pathological
      stage in localized prostate cancer patients treated with radical prostatectomy.
AB  - OBJECTIVE: Pretreatment serum level of testosterone (T) is a potential prognostic
      factor for prostate cancer. The present study was conducted to evaluate the
      clinical significance of pretreatment serum T level in patients with clinically
      localized prostate cancer. MATERIALS AND METHODS: The subjects were 82 clinically
      localized prostate cancer patients treated with radical prostatectomy, whose
      pretreatment T levels were recorded. We investigated clinical and pathological
      factors such as pretreatment serum T level, age, pretreatment PSA or pathological
      Gleason score concerning the association with pathological stage and biochemical
      recurrence. RESULTS: The mean pretreatment T level was significantly lower in
      patients with non-organ-confined prostate cancer (pT3-T4, N1; 3.44+/-1.19 ng/ml)
      than in patients with organ-confined cancer (pT2; 4.33+/-1.42 ng/ml) (p=0.0078).
      Multivariate analysis demonstrated that pathological Gleason score, pretreatment
      serum T level and pretreatment PSA were significant predictors of extraprostatic
      disease. When the patients were divided into high and low T level groups
      according to the median value, pretreatment T levels were not significantly
      associated with PSA recurrence rates (p=0.7973). CONCLUSIONS: A lower
      pretreatment T level appears to be predictive of extraprostatic disease in
      patients with localized prostate cancer.

PMID- 15716193
TI  - Fluorescence cystoscopy: is flexible scope as effective as rigid?

PMID- 15716192
TI  - Diabetes mellitus and the risk of prostate cancer in Italy.
AB  - OBJECTIVE: We investigated the relation between diabetes and the risk of prostate
      cancer, as epidemiological results are controversial. METHODS: A hospital-based
      case-control study was conducted in Italy between 1991 and 2002. Cases were 1294
      men, aged <75 years, with incident histologically confirmed prostate cancer, and
      controls were 1451 men, aged <75 years, admitted to hospital for acute non
      neoplastic diseases. Odds ratios (OR) and the corresponding 95% confidence
      intervals (CI) were estimated using unconditional multiple logistic regression
      models. RESULTS: No material association between diabetes and prostate cancer was
      observed, with a multivariate OR of 1.02 (95%CI 0.75-1.40). Prostate cancer was
      not related to time since diagnosis of diabetes (OR 0.82 and 0.97 for <5 and
      >/=15 years since diagnosis respectively). The OR were respectively 1.63 (95%CI
      0.70-3.81) and 0.96 (95%CI 0.68-1.34) in men diagnosed with diabetes at age <45
      or >/=45 years. The risk estimates were similar across strata of age at
      interview, body mass index and, among cases, of Gleason score. CONCLUSIONS: This
      study shows no material association between diabetes and prostate cancer risk.

PMID- 15716194
TI  - Comparison of hexaminolevulinate based flexible and rigid fluorescence cystoscopy
      with rigid white light cystoscopy in bladder cancer: results of a prospective
      Phase II study.
AB  - INTRODUCTION AND OBJECTIVE: Several studies have shown that rigid fluorescence
      cystoscopy (RFC) with hexaminolevulinate (HAL) is superior to standard rigid
      white light (RWLC) cystoscopy in diagnosing bladder tumours, with a clinically
      relevant impact on the patient's management. These studies, however, have been
      done with rigid cystoscopes. We carried out a study to evaluate whether the
      technique of fluorescence cystoscopy with HAL was also feasible with a specially
      designed flexible fluorescence cystoscope (FFC). METHODS: 20 patients with known
      or suspected bladder cancer were included in a comparative within patient
      controlled Phase II study. All patients signed informed consent. All patients
      received 50 ml of HAL (Hexvix) 8 mM 1h prior to transurethral resection. Using a
      D-light-C system (Storz, Germany), FFC and RFC were performed followed by RWLC.
      All lesions visible during these three cystoscopies were mapped, taped and
      resected. RESULTS: In these 20 patients (mean age 71 years (49-89), 3 females)
      mean HAL instillation time was 81 min. Overall 27 histologically confirmed
      lesions were found in 19 patients. Detection rates in these 19 patients were 14
      with FFC, 17 with RFC and 15 with RWLC. Of the 27 lesions 19 were detected with
      FFC, 23 with RFC and 20 with RWLC. Overall fluorescence intensity using the
      flexible system was 76% (30-147%) as compared to RFC using a visual analogue
      score. No side effects were noted which were attributable to HAL. CONCLUSION: The
      use of FFC is feasible and seems to be comparable to RWLC and slightly inferior
      to RFC. Larger studies should determine the role of flexible fluorescence
      cystoscopy.

PMID- 15716195
TI  - Flexible cystoscopy assisted by hexaminolevulinate induced fluorescence: a new
      approach for bladder cancer detection and surveillance?
AB  - OBJECTIVE: The aim of this study was the assessment of flexible cystoscopy
      assisted by hexaminolevulinate (HAL) fluorescence. METHODS: This study was a
      prospective controlled, within-patient comparison of flexible HAL cystoscopy with
      standard flexible cystoscopy, HAL rigid and standard white light rigid
      cystoscopy. Eligible patients received an intravesical instillation of 50 ml
      hexylaminolevulinate 8 mM solution. First flexible than rigid cystoscopy was
      performed in each patient using a Combilight PDD system (Richard Wolf, Germany),
      which provided standard white light and blue light at 375 to 440 nm, with mapping
      of all lesions detected. All tumors and suspicious areas identified under white
      light and by red fluorescence with flexible or rigid cystoscopy were then
      resected by TUR or biopsied. The specimen was assessed by an independent blinded
      pathologist. RESULTS: In the 45 patients studied 41 (91%) patients had exophytic
      tumors, of which 39 (95.1%) were detected by HAL flexible cystoscopy and 40
      (97.5%) by HAL rigid cystoscopy. 17 (37.8%) patients had concomitant or carcinoma
      in situ only, which was identified by HAL flexible cystoscopy in 14 (82.3%), by
      HAL rigid cystoscopy in 15 (88.2%), by flexible standard in 11 (64.7%) and by
      standard white light rigid cystoscopy in 13 (76.7%) patients. CONCLUSION: HAL
      fluorescence flexible cystoscopy compared to HAL rigid cystoscopy showed almost
      equivalent results in detecting papillary and flat lesions in bladder cancer
      patients. Both procedures were superior to standard white light flexible
      cystoscopy.

PMID- 15716196
TI  - The simultaneous use of telomerase, cytokeratin 20 and CD4 for bladder cancer
      detection in urine.
AB  - OBJECTIVE: Because of the low sensitivity of urinary cytological diagnosis of
      urinary bladder carcinoma, new molecular diagnostic methods have been proposed.
      We decided to verify the expression of telomerase mRNA coding for the catalytic
      component (hTRT), cytokeratin 20 (CK20) and CD4 antigen mRNAs in urine as
      possible diagnostic tool. METHODS: Evaluation of hTRT, CK20, CD4 mRNAs was
      performed in 50 ml of naturally voided urine of 205 patients of which 153 with
      bladder cancer (Tis, n = 11; TaGx, n = 4; TaG1, n = 25; TaG2, n = 26; TaG3, n =
      8; T1G1, n = 16; T1G2, n = 17; T1G3, n = 20; T2G2, n = 6; T2G3, n = 13; T3G3, n =
      7) and 52 controls. A quantitative expression of hTRT at mRNA level versus TRAP
      (telomeric repeat amplification protocol) assay was performed in 20 patients and
      14 controls. The expression of RT-PCR for hTRT, CK20, CD4 versus urinary cytology
      was analysed in 44 patients with bladder cancer. Evaluating the three molecular
      markers together, the result was considered correct when at least two of the
      markers were positive, suspected when only one marker was positive and negative
      for diagnosis of tumour when all markers were negative. The performance of the
      diagnostic model resulted from the logistic analysis evaluated with receiver
      operating characteristics (ROC) curve analysis. RESULTS: The sensitivity detected
      for each tumour marker was as follows: for hTRT 90.8%, for CK20 84.3% and for CD4
      was 64.7%, while the specificity was 94.2% for CD4 and 78.8% for both hTRT and
      CK20. When a simultaneous evaluation of the three tumour markers was considered,
      88.2% of the diagnoses were correct, 11.8% were suspected for tumour and none
      were mistaken. When compared with cytology, the simultaneous use of the three
      markers allowed reaching a correct diagnosis in 88% of the cases in comparison to
      25% by urinary cytology. The sensitivity in the detection of bladder cancer was
      higher for hTRT at mRNA level in comparison with the enzymatic activity detection
      with TRAP (90% vs. 35%) while the specificity for both markers resulted very high
      (100%). CONCLUSIONS: These data show that in the future the diagnostic
      improvement of urine based molecular markers for the detection of bladder cancer
      in the urine could improve the sensitivity of urinary cytology reducing the need
      of a cystoscopy.

PMID- 15716197
TI  - A cross-sectional study of the international prostate symptom scores related to
      age and gender in Dutch adults reporting no voiding complaints.
AB  - OBJECTIVE: To determine the IPSS in a selected population reporting no voiding
      complaints. SUBJECTS AND METHODS: 1143 adults without voiding complaints were
      included. They were divided over both sexes and all decades. All subjects filled
      out questionnaires including the IPSS. Statistical analysis was aimed at relating
      the IPSS to age and gender. RESULTS: The IPSS in both sexes shows a gradual
      significant increase in consecutive age groups. Men in the third age decade have
      a mean score of 2.8, while men older than 70 years of age have a score of 7.0. In
      women these scores are 4.0 and 5.6 respectively. The increase is about equally
      caused by storage and voiding scores. The items addressing weak stream in men and
      nocturia and urgency in men and women are the major factors causing the
      correlation with age. Nearly 17% of all subjects have moderate symptom scores and
      1% has severe scores. CONCLUSION: In both adult men and women reporting no
      voiding complaints the IPSS increases with age. This rise is more prominent in
      males.

PMID- 15716199
TI  - Development of laparoscopic surgery and training facilities in Europe: results of
      a survey of the European Society of Uro-Technology (ESUT).
AB  - OBJECTIVE: The European Society of Uro-Technology (ESUT) conducted a survey in
      order to assess the application of laparoscopy and the facilitation of training
      programs within Europe. METHODS: A total of 430 urologists and residents from
      European countries answered the ESUT survey during the XVIIIth Annual EAU Meeting
      in Madrid in 2003. The survey constituted of 11 questions of which nine with dual
      response (Y/N) options. Two questions, evaluating the importance of different
      training methods and different reasons not to be involved in laparoscopy, were
      assessed by means of a Likert type scale. RESULTS: Laparoscopy was performed in
      71% of urological departments. The majority (85%) of departments where no
      laparoscopy was performed, intended to establish it in the future. Two thirds of
      respondents believed laparoscopy would replace open surgery in the next 5 to 10
      years. The access to training facilities was insufficient for 44%. Different
      methods of training were considered to be of equal importance. Among the reasons
      for not being involved in laparoscopic surgery a high variability was identified.
      CONCLUSIONS: Laparoscopy is performed in the majority of urological departments
      in Europe. While there is a strong believe in the prominent role of laparoscopy
      in the mid-long future, access to training is still needed.

PMID- 15716198
TI  - The vasodilatory effect of alfuzosin and tamsulosin in passive orthostasis: a
      randomised, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To compare in details the effects of urologically used alpha(1)
      blockers alfuzosin and tamsulosin on the cardiovascular responses to passive
      orthostasis. METHODS: The responses to passive orthostasis (tilt provocation at
      60 degrees for 8 min) were measured in normotensive healthy volunteers with
      finger blood pressure method and whole-body impedance cardiography prior to the
      administration of the drugs as well as three days after the beginning of the
      randomised, double-blind medications. The parallel treatments were standard
      clinically used doses of alpha(1)-blockers alfuzosin (5 mg twice daily, n=10),
      tamsulosin (0.4 mg once daily, n=10), or placebo (n=11). RESULTS: When measured
      prior to the head-up tilt test in supine position, neither alfuzosin nor
      tamsulosin significantly changed any of the cardiovascular variables. During the
      passive orthostasis, however, both tamsulosin and alfuzosin reduced systemic
      vascular resistance index compared to pre-drug responses (-540 and -462
      dyns/cm(5)m(2), respectively, p<0.05). Both drugs also augmented orthostatic
      responses of heart rate (11 and 9 bpm, respectively, p<0.05) and cardiac index
      (0.50 and 0.40 l/min/m(2), respectively, p<0.05) but not those of stroke index
      when compared to the responses during placebo or before the administration of the
      drugs. The alfuzosin and tamsulosin groups did not significantly differ from each
      other in terms of any parameter. CONCLUSIONS: Both alfuzosin and tamsulosin have
      clear cardiovascular effects, which are most strikingly evident in the influences
      on systemic vascular resistance and cardiac output.

PMID- 15716200
TI  - Retroperitoneal laparoscopic radical nephrectomy for renal cell carcinoma with
      infrahepatic vena caval thrombus.
AB  - PURPOSE: The retroperitoneal laparoscopic approach is utilized to treat a right
      renal tumor with vena caval thrombus reaching infrahepatic veins. MATERIALS AND
      METHODS: The patient is an 87-year-old woman with a tumor measuring 8 x 9 cm and
      a vena caval thrombus (7 cm), stretching as far as the subhepatic vein. The
      retroperitoneal laparoscopic approach is used with the patient in the lateral
      position and the usual 4 laparoscopy trocars. A wide incision is made through
      Gerota's fascia, the renal artery clipped and severed, and the vena cava is
      dissected to the level of the infrahepatic veins; a vessel loop is encircled
      twice upstream of the thrombus. Vessel loop is similarly tied below the thrombus.
      An 8 cm abdominal wall incision is made joining two trocars on the medial and
      anterior axillary side. After retrieving the vessel loops and closing the vena
      cava by pulling gently on the loops, thrombus is extracted through a cavotomy
      under direct vision, with removal of the surgical specimen, positioning of the
      Satinsky haemostatic forceps, and closure of the vena cava using uninterrupted
      Prolene 2/0 sutures. RESULTS: Blood loss was 300 cc. The patient was discharged
      on day 6, and a CT-scan 4 months later disclosed no signs of recurrence.
      CONCLUSIONS: This is an original solution that opens the way to further
      indications for using retroperitoneal laparoscopy to treat tumors extending into
      the inferior vena cava.

PMID- 15716201
TI  - Port-site metastasis: the influence of biology.
AB  - OBJECTIVE: Several surgical and technical mechanisms have been proposed for the
      development of port-site metastasis, but the influence of tumor and host biologic
      factors has not been emphasized. We present a case of a pelvic chordoma that
      metastasized to a prior laparoscopic radical nephrectomy port-site. METHODS: A 62
      year-old woman underwent laparoscopic radical nephrectomy (LRN) for a pT1b grade
      3 renal cell carcinoma, followed 6 weeks later by resection of a sacral chordoma.
      The incisions and areas of dissection for the two procedures were discontinuous.
      RESULTS: Eight months following the LRN she developed a nodule in one of the
      laparoscopic port-sites. The port-site metastasis was treated with wide surgical
      resection, which was confirmed as metastatic chordoma on histologic examination.
      CONCLUSION: Based on the chronological sequence and physical distance between
      surgical sites, only biological factors could have contributed to this port-site
      metastasis. This unusual case highlights the important role that tumor and host
      biologic mechanisms play in the development of port-site metastasis.

PMID- 15716202
TI  - The utility of tamsulosin in the management of orgasm-associated pain: a pilot
      analysis.
AB  - INTRODUCTION: Orgasmic pain is an infrequently reported but distressing problem
      for the patients who experience it. No consensus exists as to its etiology
      however bladder neck/pelvic floor spasm may play a role. This analysis was
      conducted to assess the effect of the alpha-blocking medication, tamsulosin on
      post-orgasmic pain. METHODS: In a prospective, non-placebo controlled study,
      patients with orgasmic pain were interviewed and administered tamsulosin 0.4 mg
      po qhs for at least 4 weeks. Outcome measures included libido, pain and
      continence and these were evaluated using the International Index of Erectile
      Function (IIEF), a visual analog scale (VAS) for pain and an incontinence scale
      respectively pre and post treatment. Patients were separated into groups based on
      etiology of the problem (radical prostatectomy, radiation therapy, and other) for
      statistical analysis. RESULTS: 98 patients were enrolled. Pain was located
      predominantly in the penis (72%), with other sites including testis, rectum and
      abdomen. Most patients (52%) experienced pain for less than 5 minutes post
      orgasm. 76/98 (77%) patients reported significant improvement in pain (>/=2
      points on pain VAS) and 12/98 (12%) noted complete resolution of their pain. The
      VAS for pain reflected a statistically significant decrease in pain for all
      groups in response to tamsulosin treatment. The entire group had a decrease of
      2.7 points between pre and post-treatment phases. The IIEF libido domain
      increased significantly (mean of 2.4 points) for all treatment groups.
      CONCLUSION: Tamsulosin decreases orgasmic pain intensity in patients with
      orgasmic pain. These data support the hypothesis that orgasmic pain is related to
      bladder neck and/or pelvic floor muscle spasm.

PMID- 15716203
TI  - Female sexual dysfunction in a healthy Austrian cohort: prevalence and risk
      factors.
AB  - PURPOSE: Data on prevalence and risk factors for female sexual dysfunction (FSD)
      are rare, particularly from Europe. Aim of our study was therefore to investigate
      this issue in a cohort of women undergoing a health investigation. PATIENTS AND
      METHODS: A consecutive series of women aged 20-80 years participating in a health
      screening project in Vienna underwent a detailed health investigation and
      completed a 23-item questionnaire on several aspects of FSD including desire,
      arousal, pain and orgasmic disorders. Prevalence of FSD in different age groups
      and risk factors for FSD were calculated. RESULTS: A total of 703 women aged 43+/
      15 years entered this study. Within the total study population, 22% reported on
      desire disorders, 35% on arousal disorders, and 39% on orgasmic problems, all of
      which increased significantly with age. Pain disorders were reported by 12.8%
      being most frequently in the women aged 20-39 years. In women aged 60-69 years,
      still 50% reported having at least "occasionally" sexual desire and 30% had more
      than two sexual intercourses per month. In this age group, 50% stated that a
      healthy sexual life is at least moderately important to them. Apart from age few
      risk factors for FSD were identified. Sportive activity was the only correlate to
      desire- and arousal disorders, psychological stress for orgasmic disorders.
      CONCLUSIONS: This study provides insights into age-specific changes of FSD in
      apparently healthy women. The importance of this subject is underlined by the
      high prevalence of FSD particularly in the elderly paralleled by a persisting
      interest in sexual activity.

PMID- 15716204
TI  - Long-term open-label solifenacin treatment associated with persistence with
      therapy in patients with overactive bladder syndrome.
AB  - OBJECTIVE: To examine safety and tolerability findings as primary endpoints, and
      efficacy outcomes as secondary endpoints, of solifenacin treatment over a period
      of up to 1 year. Long-term efficacy in the treatment of overactive bladder (OAB)
      syndrome depends in part on the patient's persistence with pharmacologic therapy.
      Agents with a favourable therapeutic index supporting high levels of patient
      satisfaction and persistence are needed. METHODS: The present study was a 40-week
      open-label extension of two 12-week, placebo-controlled, double-blind studies of
      solifenacin treatment in patients with OAB. Patients who completed the 12-week
      studies were offered participation in the open-label extension study. All
      patients who entered the open-label extension study initially received
      solifenacin 5 mg daily for 4 weeks, after which a flexible dosing regimen allowed
      patients to individualise their treatment (5 mg or 10 mg) at each of the 3 study
      visits. Safety and tolerability assessments (the primary variable) included
      adverse event reporting. Efficacy data were collected from micturition diaries
      completed at weeks 16, 28, 40, and 52. RESULTS: Ninety-one percent (1637/1802) of
      patients who completed the two 12-week randomised studies chose to participate in
      the long-term open-label extension study. A total of 81% of patients completed 40
      weeks of open-label treatment. Solifenacin treatment was safe and well tolerated,
      and rates of anticholinergic side effects were relatively low. Only 4.7% of
      patients discontinued treatment owing to adverse events. Improvements in major
      symptoms of OAB were noted for all patients for up to 52 weeks of treatment. In
      patients randomised to solifenacin in the double-blind studies, there were small
      incremental improvements in all efficacy parameters (reductions in episodes per
      24 hours of urgency, reductions in frequency and urge incontinence, and increases
      in volume voided per micturition) over the course of the extension study.
      Efficacy was confirmed when outcomes were assessed as a function of total
      solifenacin exposure. Patient satisfaction with solifenacin tolerability (85%)
      and efficacy (74%) were high. These results indicate that long-term treatment
      with solifenacin was well tolerated and associated with improvements in efficacy
      parameters based on patient diary data recorded over the 12-month treatment
      period. Moreover, the high level of patient satisfaction reported appeared to
      correlate well with the quantified improvements in key symptoms demonstrated in
      this study. CONCLUSIONS: Long-term therapy with solifenacin resulted in a
      favourable tolerability profile, and was associated with improvements in efficacy
      parameters based on diary data recorded over a 12-month period. This balance of
      tolerability and efficacy with solifenacin was associated with excellent
      persistence with therapy. These results suggest that solifenacin may be useful
      for the long-term treatment of the chronic symptoms associated with OAB.

PMID- 15716205
TI  - Help-seeking behaviour and associated factors among women with urinary
      incontinence in France, Germany, Spain and the United Kingdom.
AB  - OBJECTIVES: To assess the proportion of women who consult their doctor about
      urinary incontinence (UI), and explore factors associated with help-seeking in
      France, Germany, Spain and the UK. METHODS: A representative sample of 29,500
      women received a 13 item postal questionnaire to identify those with UI. A
      randomly selected sub-sample of 2953 women with UI received a more detailed
      follow-up questionnaire. RESULTS: There was a response rate of 58% in the initial
      survey and 53% in the second. Thirty-one percent of all women had consulted a
      doctor about their UI symptoms with more women consulting in France and Germany
      than in the UK and Spain. A number of factors relating to general health care, UI
      and women's attitudes were found to be associated with help-seeking after
      adjusting for women's age, UI duration and frequency, and 'bothersomeness' of UI;
      factors traditionally associated with help-seeking. After adjusting for these
      factors, willingness to take long-term medication and having spoken to others
      about UI were found to be strong predictors of help-seeking in all four
      countries.

PMID- 15716206
TI  - Do cystometric findings predict the results of intravesical hyaluronic acid in
      women with interstitial cystitis?
AB  - INTRODUCTION AND OBJECTIVES: According to National Institute of Health (NIH)
      criteria, a bladder capacity of less than 350 cc is an automatic exclusion for a
      diagnosis of Interstitial Cystitis (IC). In the present study, patients, showing
      symptoms of IC and with bladder capacities of <350 and >/=350 cc were tested as
      to their response to a intravesical hyaluronic acid therapy. METHODS: The study
      included 48 patients with clinical symptoms of IC and a positive 0.4 M potassium
      sensitivity test. Maximum bladder capacity (C(max)) was assessed for the 0.9%
      NaCl solution first and then for the 0.2 M KCl solution. After the NaCl
      cystometry, patients were separated into two groups: Group I with a C(max) of
      <350 cc and Group II with a C(max) of >/=350 cc. Both groups were again separated
      in two further groups as to the respective percentage reduction of C(max) with
      the 0.2 M KCl solution: Group Ia/IIa (>/=30%) and Group Ib/IIb (<30%). Patients
      were treated with weekly instillations of 40 mg hyaluronic acid for 10
      consecutive weeks. Pre- and post-treatment bladder symptoms were evaluated
      through their visual analog scale (VAS) scores. RESULTS: With the saline
      solution, 32 patients had a C(max) of <350 cc (Group I), while 16 patients had a
      C(max) of >/=350 cc (Group II). Evaluation of VAS scores confirmed a positive
      response, i.e. symptom relief, to hyaluronic acid therapy, irrespective of
      bladder capacity. The improvement was particularly evident in patients with a
      C(max) reduction of >/=30% versus those with a reduction of <30% with the 0.2 M
      KCl solution (p=0.003). CONCLUSION: The present study demonstrates that patients
      with typical IC symptoms and a cystometric bladder capacity of >/=350 cc, may
      have increased potassium sensitivity as a sign of IC and show symptom improvement
      after hyaluronic acid instillation therapy.

PMID- 15716207
TI  - Impact of sex reassignment surgery on lower urinary tract function.
AB  - OBJECTIVE: To investigate the effects of sex reassignment surgery (SRS) on lower
      urinary tract function. METHODS: A questionnaire concerning voiding habits and
      lower urinary tract symptoms after sex reassignment surgery, was given to 24
      female-to-male transsexuals (FTM) and 31 male-to-female transsexuals (MTF), who
      respectively underwent phalloplasty and vaginoplasty. For this study only Dutch
      speaking patients were selected. Also, uro-flowmetry data from 92 FTM
      transsexuals were reviewed. RESULTS: In general, no change in voiding patterns
      was observed. Post-void dribbling was reported by 79% of the FTM transsexuals,
      and 16% of the MTF group reported some form of incontinence. The uro-flowmetry
      examination showed a mean, non-significant decrease of 2 ml/s in Q(max) in FTM
      patients. CONCLUSION: SRS can cause minor changes in urinary habits. Even if they
      do not result in patients seeking medical help, transsexuals should be warned
      about these eventual discomforts pre-operatively.

PMID- 15716208
TI  - Decompression and transposition of the pudendal nerve in pudendal neuralgia: a
      randomized controlled trial and long-term evaluation.
AB  - BACKGROUND: We assess that pudendal neuralgia is a tunnel syndrome due to a
      ligamentous entrapment of the pudendal nerve and have treated 400 patients
      surgically since 1987. We have had no major complication. We conducted a
      randomized controlled trial to evaluate our procedure. METHODS: A sequential,
      randomized controlled trial to compare decompression of the pudendal nerve with
      non-surgical treatment. Patients aged 18-70, had chronic, uni/bilateral perineal
      pain, positive temporary response to blocks at the ischial spine and in Alcock's
      canal. They were randomly assigned to surgery (n=16) and control (n=16) groups.
      Primary end point was improvement at 3 months following surgery or assignment to
      the non-surgery group. Secondary end points were improvement at 12 months and at
      4 years following surgical intervention. RESULTS: A significantly higher
      proportion of the surgery group was improved at 3 months. On intention-to-treat
      analysis 50% of the surgery group reported improvement in pain at 3 months versus
      6.2% of the non-surgery group (p=.0155); in the analysis by treatment protocol
      the figures were 57.1% versus 6.7% (p=.0052). At 12 months, 71.4% of the surgery
      group compared with 13.3% of the non-surgery group were improved, analyzing by
      treatment protocol (p=.0025). Only those randomized to surgery were evaluated at
      4 years: 8 remained improved at 4 years. No complications were encountered.
      CONCLUSIONS: In this study we demonstrate that decompression of the pudendal
      nerve is an effective and safe treatment for cases of chronic pudendal neuralgia
      that have been unresponsive to analgesia and nerve blocks. Following surgery,
      other medical interventions may be necessary.

PMID- 15716209
TI  - Testosterone regulates PDE5 expression and in vivo responsiveness to tadalafil in
      rat corpus cavernosum.
AB  - OBJECTIVES: To investigate the effect of testosterone on PDE5 expression and PDE5
      inhibitor tadalafil in vivo responsiveness in a rat model. METHODS: PDE5
      expression was localized by immunohistochemistry in the rat corpus cavernosum
      (CC) and quantified by both real-time RT-PCR and Western blot analysis in several
      tissues. In the in vivo study, control, castrated and testosterone (T)
      supplemented castrated rats were treated with acute or chronic oral tadalafil.
      Erectile function was evaluated by monitoring intracavernous pressure (ICP)
      following electro-stimulation (ES) of the cavernous nerve and intracavernous
      injection of NO donor, sodium nitroprusside (SNP). RESULTS: Rat CC expressed the
      highest PDE5 mRNA level. PDE5 was specifically immunolocalized in endothelial and
      smooth muscle cells. Surgical castration induced a significant reduction of PDE5
      gene and protein expression (p<0.05), and ES response at all stimulation
      frequencies (p<0.001). T supplementation completely restored PDE5 expression,
      erectile response to ES and responsiveness to PDE5 inhibitor. Both acute and
      chronic tadalafil treatment were ineffective in ameliorating the ES response in
      castrated rats. Injection of increasing concentrations of SNP in castrated rats
      resulted in a statistically significant increase in ICP/MAP ratio as that
      observed in intact rats. In addition, tadalafil did not amplify the SNP effect in
      castrated rats at all the doses tested (0.06-6 nmoles). CONCLUSIONS: Our findings
      demonstrate that testosterone positively regulates PDE5 expression and in vivo
      responsiveness to PDE5 inhibitor, tadalafil, in the rat CC.

PMID- 15716210
TI  - Comparison of angiogenic activities after urethral reconstruction using free
      grafts in rabbits.
AB  - OBJECTIVE: To determine the most suitable type of graft-free penile skin grafts
      or mucosal grafts from bladder or buccal regions - for urethral reconstruction in
      an animal model, as evaluated on the basis of angiogenic activity. METHODS:
      Twenty-two male White New Zealand rabbits were randomly divided into four groups.
      In the control group (group O, n=4) a simple urethrotomy and closure was
      performed, whereas a ventral urethral defect was created in groups A, B, and C
      and then bridged using the following onlay patches: free penile skin (group A,
      n=6), buccal mucosal graft (group B, n=6), and bladder mucosal graft (group C,
      n=6). On the 21st postoperative day, the animals were sacrificed and the
      retrieved implants were subjected to macroscopic and microscopic analysis. The
      angiogenic activity was assessed with immunohistochemistry, using the anti-CD31
      MoAb and the phosphatase antialkaline phosphatase procedure. The native
      vascularity of penile skin as well as buccal and bladder mucosa was assessed in
      rabbits from group O (n=3). Statistical analysis was performed using the one-way
      ANOVA. RESULTS: The angiogenesis in a magnification of x200 in groups O, A, B,
      and C was 34.1+/-4.1 (mean+/-SD), 61.7+/-6.4, 94.3+/-6.4, and 91.5+/-7.2 vessels
      per optical field, respectively. There were, statistically significant
      differences (p<0.001) between groups A and B and between groups A and C, but not
      (p>0.05) between groups B and C. The native vascularity of penile skin, buccal
      mucosa and bladder mucosa was 23.3+/-3.0, 24.6+/-3.7 and 17.0+/-2.6 vessels per
      optical field, respectively. CONCLUSION: The viability of mucosal grafts from
      bladder or buccal regions is better than that of a free penile graft because of
      higher angiogenic activity. Although the mucosal grafts showed the same
      angiogenic activity, the buccal mucosa graft is preferable because of its easier
      harvesting.

PMID- 15716212
TI  - Re: Weckermann D, Harzmann R. Hormone therapy in prostate cancer: LHRH
      antagonists versus LHRH analogues. Eur Urol 2004;46:279-84.

PMID- 15716213
TI  - Enhanced external counter pulsation (EECP) as a novel treatment for restless legs
      syndrome (RLS): a preliminary test of the vascular neurologic hypothesis for RLS.
AB  - BACKGROUND AND PURPOSE: Enhanced external counter pulsation (EECP) is used to
      treat angina. With sustained treatment this increases collateral circulation to
      the coronary arteries as well as to the body as a whole. We found some patients
      who underwent EECP for angina or congestive heart failure who also coincidentally
      had severe Restless Legs Syndrome (RLS). Case reports are presented. PATIENTS AND
      METHODS: Six patients with RLS (1F, 5M, ages 55-80) underwent EECP treatment. All
      patients were given the International RLS Study Group rating scale for RLS (the
      IRLS) before and immediately after 35 days of EECP treatment. RESULTS: The
      average IRLS rating scale score of the six patients before treatment was 28.8
      (range 23-35), which indicates frequent and moderate to very severe RLS. After 35
      days of EECP treatment the IRLS score was 6 (P<0.03), which indicates clinically
      insignificant RLS. Long-term follow-up in three patients indicates sustained
      improvement in all three at 3-6 months after EECP was completed (IRLS score 28.3
      3.33). Further follow-up in four patients showed sustained improvement in two
      patients 1 year after EECP was completed. CONCLUSION: EECP improves RLS symptoms
      significantly and could be considered as an adjunct treatment for patients with
      RLS. In some cases, the improvement lasts for months after the course of
      treatment. In this way EECP is unique and unlike pharmacotherapy which requires
      continuous daily treatment. Furthermore, our results suggest that decreases in
      vascular flow influence the peripheral or central nervous system leading to the
      sensory symptoms of RLS. A larger number of patients studied under blinded
      conditions is needed to draw further conclusions.

PMID- 15716214
TI  - Long-term use of sedative hypnotics in older patients with insomnia.
AB  - BACKGROUND AND PURPOSE: Insomnia is a common problem that increases with age and
      can last months to years. While substantial data establish the efficacy and
      safety of short-acting hypnotic therapy for the management of short-term insomnia
      using benzodiazepines receptor agonists (BzRAs), there are few studies on the
      continued efficacy and safety of these drugs when used for sustained periods.
      This paper reports the results of a 1-year open-label extension phases of two
      randomized, double-blind trials of zaleplon. PATIENTS AND METHODS: In the open
      label phase, older patients self-administered zaleplon nightly from 6 to 12
      months and were then followed through a 7-day single-blind placebo-controlled run
      out period. RESULTS: The safety profile in this population of older adults was
      similar to that observed in a short-term trial of an equivalent population. The
      data also suggested that long-term therapy produced and maintained statistically
      significant improvement in time to persistent sleep onset, duration of sleep and
      number of nocturnal awakenings (P<0.001 for each variable) for treatment
      durations of up to 12 months. Discontinuation was not associated with rebound
      insomnia. CONCLUSION: The open-label trial of long-term hypnotic therapy with
      zaleplon 5 and 10 mg suggests that they are safe and effective for the treatment
      of insomnia in older patients. Placebo-controlled, double-blind trials are needed
      in zaleplon and other BzRAs to confirm these results.

PMID- 15716215
TI  - Examining the construct of depression in obstructive sleep apnea syndrome.
AB  - BACKGROUND AND PURPOSE: Depression is commonly reported by patients suffering
      from Obstructive Sleep Apnea Hypopnea Syndrome (OSAS). We used the factor
      structure of the Beck Depression Inventory-2nd edition (BDI-II) to examine the
      unique contributions of OSAS severity and obesity to depressive symptoms in OSAS.
      We predicted that the Somatic and Cognitive dimensions of the BDI-II would be
      more strongly associated with apnea severity and obesity, respectively. PATIENTS
      AND METHODS: Ninety-three moderate to severe OSAS patients (61 men, 32 women)
      were seen for psychological testing prior to initiating CPAP treatment. They
      completed the BDI-II and Epworth Sleepiness Scale (ESS). Measures of apnea
      severity (RDI, percent of sleep time below 90% oxygen saturation) and BMI were
      also collected. RESULTS: RDI was significantly related to BMI and BDI-II total
      score, but not to ESS score. BMI was related to BDI-II total score and ESS score.
      Partial correlations indicated that RDI was independently related to the Somatic
      dimension on the BDI-II. By contrast, BMI was uniquely associated with the
      Cognitive dimension. Although there was no difference in depression scores
      between men and women, the relationship between the Somatic factor and apnea
      severity was significant in men, whereas obesity and the Cognitive factor were
      significantly associated in women. CONCLUSIONS: OSAS severity and obesity
      contribute differentially to symptoms of depression in OSAS. In addition,
      symptoms of depression in OSAS manifest differently in men than in women.

PMID- 15716216
TI  - Immediate consequences of respiratory events in sleep disordered breathing.
AB  - BACKGROUND: In obstructive sleep apnea/hypopnea syndrome, immediate physiological
      consequences of events have a dual role: censoring artifacts and gauging
      physiological significance. Newer airflow monitors may have changed the relative
      importance of these functions. The purpose of this study was to determine the
      frequency and hierarchy of occurrence of oxygen desaturation, EEG arousal and
      heart rate changes as immediate consequences of respiratory events. METHODS:
      Thirty-nine sleep apnea patients underwent polysomnography with airflow detection
      by nasal cannula. Eighty events/subject were randomly selected and evaluated for
      4% oxygen desaturation, EEG arousal and heart rate increase. RESULTS: Of apneas,
      78% caused desaturation, 63% arousal, and 73% heart rate increase. Of hypopneas,
      54% caused desaturation, 47% arousal, and 55% heart rate increase. Of events with
      mildest amplitude reduction 25% caused desaturation, 42% arousal, and 42% heart
      rate increase. Consequences overlapped but did not occur hierarchically: each
      occurred alone and in all combinations. CONCLUSION: No single consequence
      occurred after every event; thus none can be used to corroborate airflow
      reduction as non-artifactual without missing events corroborated by other
      consequences. As different consequences validate non-hierarchical sets of
      respiratory events, we propose there is need to capture all changes in breathing
      in obstructive sleep apnea/hypopnea syndrome before examining their role in
      clinical outcome.

PMID- 15716217
TI  - Randomized, double-blind, placebo-controlled, short-term trial of ropinirole in
      restless legs syndrome.
AB  - BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a condition characterized
      by an urge to move the legs, usually accompanied by lower limb paresthesias.
      These symptoms worsen at rest, are relieved by activity, and are worse at night.
      Previous studies have suggested that dopaminergic drugs such as L-dopa and
      dopamine agonists, as well as benzodiazepines and opioids, can treat RLS
      successfully. The purpose of this study was to test the clinical efficacy of
      ropinirole, a D2/D3 agonist, in the treatment of RLS in a double-blind, short
      term, placebo-controlled clinical trial. PATIENTS AND METHODS: After undergoing
      successful open-label titration and dose adjustments with ropinirole for RLS
      symptoms over a period of 4 weeks, 22 RLS patients (mean age=50.8; mean duration
      of symptoms=26.1 years) were randomized to receive either placebo (n=13) or
      ropinirole (n=9) for 2 additional weeks. Outcome measures included assessment of
      periodic leg movements in sleep (PLMS) recorded with nocturnal polysomnography
      and RLS symptoms as assessed with the International Restless Legs Syndrome Study
      Group (IRLSSG) Rating Scale. Secondary outcomes included sleep macroarchitecture.
      RESULTS: Results indicated that relative to placebo, ropinirole, at a mean dose
      of 1.4mg HS significantly decreased PLMS and RLS symptoms. Sleep
      macroarchitecture did not change. Side effects were typical of all dopamine
      agonists and were dose related. The majority of patients elected to continue
      treatment with ropinirole upon study completion. CONCLUSIONS: Ropinirole
      successfully treated long-standing RLS and can be considered a viable short-term
      treatment for this condition.

PMID- 15716218
TI  - Sleep disturbances in patients treated for panic disorder.
AB  - BACKGROUND AND PURPOSE: Disturbed night sleep is a common complaint of patients
      with panic disorder. The aim of the present study was to demonstrate whether the
      sleep disturbances can be successively influenced by the standard therapy for
      treating panic disorder. PATIENTS AND METHODS: Psychiatric examinations of 20
      outpatients with panic disorder were supplemented with a study of sleep quality
      using standardised interviews, sleep logs and polysomnographic recordings.
      RESULTS: A statistical comparison of data showed that reduced anxiety after
      successful treatment of panic disorder was not necessarily followed by improved
      sleep parameters. CONCLUSION: The results suggest that the conventional therapy
      applied to these patients is not sufficient to treat the co-existing insomnia.
      Consequently, it seems to be of importance to supplement the treatment of panic
      disorders with specific treatment of the sleep disturbance.

PMID- 15716219
TI  - The spontaneous eye-blink as sleepiness indicator in patients with obstructive
      sleep apnoea syndrome-a pilot study.
AB  - BACKGROUND AND PURPOSE: To evaluate the spontaneous eye-blink as
      drowsiness/sleepiness indicator in patients with obstructive sleep apnoea (OSA)
      syndrome. PATIENTS AND METHODS: Using a contact-free sensor for the recording of
      spontaneous eye-blinks, we investigated the diagnostic value of spontaneous blink
      parameters in 21 OSA patients. Before the study, all patients underwent a night
      of polysomnography. Eye-blinks were studied the following morning before therapy,
      and again after the first therapy night with nasal continuous positive airway
      pressure (nCPAP), to investigate whether blink parameters reflected changes of
      alertness pre- and post-nCPAP treatment. General daytime sleepiness was assessed
      using the Epworth Sleepiness Scale (ESS). The current subjective state was
      determined by means of standardised questionnaires directly before recording the
      eye-blinks. Studies were conducted in two sleep laboratories in hospitals.
      RESULTS: In OSA patients with excessive daytime sleepiness (EDS; ESS >10,
      respiratory disturbance index [RDI]=42.4) several parameters proved informative
      for sleepiness diagnostics. Reduction of blink duration and reopening time as
      well as increase in blink frequency were significant; furthermore, proportion of
      long-closure duration blinks indicated reduced sleepiness. OSA patients without
      EDS (ESS < or =10, RDI=33.5) did not reveal systematic changes of the blink
      parameters registered after one night of nCPAP intervention. CONCLUSIONS:
      Specific parameters of the spontaneous eye-blink may be applied as a sleepiness
      index for diagnostics in OSA patients. Further studies are needed to prove the
      diagnostic value of blink parameters and their advantages in comparison to
      subjective measures commonly used in clinical studies.

PMID- 15716220
TI  - Sleep complaints: snoring and daytime sleepiness in pregnant and pre-eclamptic
      women.
AB  - BACKGROUND AND PURPOSE: To examine whether snoring and sleepiness are linked in
      pregnancy and pre-eclampsia. PATIENTS AND METHODS: We recruited 167 healthy and
      82 pre-eclamptic women in the third trimester of pregnancy and 160 non-pregnant
      women. Subjects and their partners completed a sleep questionnaire. Height,
      weight, neck circumferences and blood pressure were recorded for all. RESULTS:
      Pregnant and pre-eclamptic women were (mean +/-SD) 36+/-3.6 and 36+/-3 weeks
      pregnant, respectively. Age and height did not differ significantly between
      groups (P>0.2), but pre-eclamptic women were heavier than pregnant and non
      pregnant women and had higher BMI than pregnant women before pregnancy (all
      P<0.05). Thirty-two percent of control, 55% of pregnant and 85% of pre-eclamptic
      women snored (P<0.001), but pre-pregnancy snoring rates (pre-eclamptic=36%,
      healthy pregnant women=27%) were similar to those in non-pregnant women (32%)
      (P>0.7). Sleepiness was reported by 12% of non-pregnant, 23% of pregnant and 15%
      of pre-eclamptic women (P<0.04), but non-pregnant women had lower mean Epworth
      Sleepiness scores than both pregnant and pre-eclamptic groups (P<0.001). Snoring
      was correlated with (P=0.002), but explained only <2%, of the variance in
      sleepiness. CONCLUSION: Snoring and sleepiness increased in the third trimester
      of pregnancy, particularly in patients with pre-eclampsia. However, the study
      suggests that sleepiness in pregnancy is largely due to factors other than
      snoring or breathing pauses.

PMID- 15716221
TI  - CPAP compliance: video education may help!
AB  - BACKGROUND: CPAP remains the treatment of choice for Obstructive Sleep Apnea
      Hypopnea Syndrome (OSAHS), but compliance with CPAP is poor. Of many
      interventions tried to improve CPAP compliance, only education and humidification
      have been shown to be of benefit. Our purpose was to develop and pilot test a
      video to enhance patient understanding of obstructive sleep apnea and of the
      purpose, logistics, and benefits of CPAP use in patients newly diagnosed with
      OSAHS. A patient's CPAP compliance in the first few weeks after starting its use
      is predictive of long-term compliance with CPAP treatment. It is imperative that
      patients grasp at the outset both the severity of OSAHS and the effectiveness of
      CPAP therapy. METHODS: An educational video script was written based on
      recommendations for patient educational video materials and covering identified
      misconceptions about OSAHS and perceived barriers to CPAP use. The videotape is
      15 min in length and features two middle-aged males, one African-American and one
      Euro-American, discussing OSAHS and CPAP in a factory break room. RESULTS: In a
      randomized two-group design with a control group, patients with newly diagnosed
      OSAHS, and who viewed the CPAP educational video on their first clinic, were
      significantly more likely to use their machine and to return for a 1-month clinic
      visit than were those in the control group. CONCLUSION: Viewing of a patient
      education video at the initial visit was found to significantly improve the rate
      of return for the follow-up visit.

PMID- 15716223
TI  - Effect of added dead space to positive airway pressure for treatment of complex
      sleep-disordered breathing.

PMID- 15716224
TI  - [Reverse sleep state misperception].

PMID- 15716226
TI  - Functional MRI during sleep: arousal and anti-arousal responses.

PMID- 15716227
TI  - Clinical significance of (sessile) serrated adenomas: Another piece of the
      puzzle.

PMID- 15716228
TI  - Clinically significant Kluyvera infections: a report of seven cases.
AB  - To determine the clinical significance of Kluyvera isolates at our institution,
      we retrospectively analyzed clinical microbiology data from January 1999 to
      September 2003. We identified 11 isolates classified as Kluyvera ascorbata, 7 of
      which were considered clinically significant pathogens: 3 cases represented
      urinary tract infections; 2, bacteremia; 1, a soft tissue infection of the
      finger; and 1, acute appendicitis with a subsequent intra-abdominal abscess. The
      age distribution of patients was wide, ranging from 2 months to 73 years.
      Antimicrobial susceptibility studies of the clinically significant and non
      clinically significant Kluyvera isolates showed susceptibility patterns similar
      to those reported in the medical literature, namely trends of resistance to
      ampicillin and first- and second-generation cephalosporins. Of the 4 non
      clinically significant isolates in our study, 1 was resistant to ciprofloxacin, a
      finding reported in only 1 other isolate of Kluyvera in the medical literature.
      Patient outcome after treatment with third-generation cephalosporins and
      aminoglycosides in the 7 clinically significant cases was good, with no long-term
      sequelae. The potential virulence of K ascorbata highlights the need for
      heightened scrutiny of its antimicrobial susceptibility patterns for adequate
      clinical treatment.

PMID- 15716229
TI  - Broad-range (pan) Salmonella and Salmonella serotype typhi-specific real-time PCR
      assays: potential tools for the clinical microbiologist.
AB  - We describe broad-range salmonellae (ie, Salmonella) and Salmonella serotype
      Typhi-specific LightCycler (Roche Diagnostics, Indianapolis, IN) real-time
      polymerase chain reaction assays. We validated these with a battery of 280
      bacteria, 108 of which were salmonellae representing 20 serotypes. In addition,
      298 isolates from 170 clinical specimens that were suspected to possibly
      represent Salmonella were tested with the pan- Salmonella assay. Finally, the pan
      Salmonella assay also was used to test DNA extracts from 101 archived, frozen
      stool specimens, 55 of which were culture-positive for salmonellae. Both assays
      were 100% sensitive and specific when cultured isolates of the battery were
      tested. The pan- Salmonella assay also characterized correctly all salmonellae on
      the primary isolation agar and was 96% sensitive (53/55) and 96% specific (49/51)
      when nucleic acid extracts from direct stool specimens were tested. These assays
      represent potential tools the clinical microbiologist could use to screen suspect
      isolates or stool specimens for Salmonella.

PMID- 15716230
TI  - The risk of metachronous neoplasia in patients with serrated adenoma.
AB  - Serrated adenomas are the precursors of at least 5.8% of colorectal cancers;
      otherwise little is known of their clinical significance in comparison with
      conventional adenomas and hyperplastic polyps. We compared the risk of
      metachronous lesions in colorectal serrated adenomas, conventional adenomas, and
      hyperplastic polyps. A consecutive series of patients with colorectal polyps
      first diagnosed from January 1978 to December 1982 and follow-up specimens to the
      end of 2000 was reviewed, and 239 polyps fulfilling the selection criteria were
      chosen as index polyps. The type of polyp seen in follow-up correlated
      significantly with the type of the initial lesion. Serrated adenomas were
      estimated to grow faster than conventional adenomas, but the incidence of
      colorectal cancer did not differ significantly between serrated (2/38 [5%]) and
      conventional adenomas (2.2%). The results indicate that serrated adenomas are
      lesions with a significant risk of metachronous serrated adenomas and the
      development of cancer. We emphasize the need for the proper recognition and
      management of serrated adenomas.

PMID- 15716231
TI  - Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in
      effusions.
AB  - We immunohistochemically analyzed kallikrein 4 protein (hK4) expression in
      patients with epithelial ovarian carcinoma (181 malignant effusions and 103 solid
      carcinoma lesions). Expression of hK4 was also studied in 32 effusions using
      immunoblotting. Carcinoma cells expressed hK4 in 144 (79.6%) of 181 effusions and
      85 (82.5%) of 103 solid tumors. Expression was seen in 51% or more of tumor cells
      in 70 effusions but often was limited to 5% or fewer cells in solid tumors (P =
      .009, primary tumors vs effusions; P = .002, metastases vs effusions).
      Immunoblotting showed hK4 expression in 31 of 32 specimens. Stromal cell hK4
      expression, seen in 48 (46.6%) of 103 lesions, was significantly higher in
      primary tumors than metastases (26/43 vs 22/60, P = .019). hK4 expression in
      tumor cells was significantly lower in International Federation of Gynecology and
      Obstetrics stage IV than stage III tumors (P = .004, all lesions; P = .012,
      primary tumors). hK4 expression in carcinoma cells was associated with longer
      overall survival (not significant; P = .14, peritoneal effusions). hK4 is
      expressed widely in ovarian carcinoma; levels in carcinoma cells are highest in
      effusions, which might be related to loss of stromal contribution and/or altered
      microenvironment. hK4 expression in carcinoma cells of effusions or solid tumors
      does not predict survival.

PMID- 15716232
TI  - Cystic tumor of the atrioventricular node of the heart appears to be the heart
      equivalent of the solid cell nests (ultimobranchial rests) of the thyroid.
AB  - We studied a series of 10 solid cell nests (SCNs) of the thyroid and a case of
      cystic tumor of the atrioventricular node (CTAVN) of the heart and reviewed the
      literature. The CTAVN and SCNs appeared as cystic and/or solid (squamoid)
      structures mainly composed of polygonal or oval cells (main cells) admixed with
      occasional clear cells (neuroendocrine and C cells). Main cells were
      immunoreactive for simple and stratified epithelial-type cytokeratins, epithelial
      membrane antigen, carcinoembryonic antigen, carbohydrate antigen 19.9, p63, bcl
      2, and galectin-3. Neuroendocrine (and C) cells were positive for simple-type
      cytokeratins, carcinoembryonic antigen, calcitonin, chromogranin, synaptophysin,
      and thyroid transcription factor-1. Our data support the hypothesis that the
      CTAVN of the heart and the SCNs of the thyroid are identical structures that
      represent the same lesional process. The assumption that CTAVN is a
      ultimobranchial heterotopia fits with the known role of cardiac neural crest
      cells in cardiovascular development.

PMID- 15716233
TI  - Expression of hard alpha-keratins in pilomatrixoma, craniopharyngioma, and
      calcifying odontogenic cyst.
AB  - To examine the properties of shadow and ghost cells, 3 kinds of antibodies were
      raised against human hair proteins and their immunoreactivity was examined in
      tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17
      cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2
      polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic
      and type II neutral/basic hard alpha-keratins. The other monoclonal antibody, MA
      HP1, reacted with type II neutral/basic hard alpha-keratins. Immunohistochemical
      examination revealed that all 3 antibodies reacted only with the hair shaft in
      sections of normal skin and dermoid cyst. In all pilomatrixoma cases, 3
      antibodies reacted with the cytoplasm of transitional and shadow cells but not
      with that of basophilic cells. Positive reactions were found only in shadow cells
      of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies
      reacted only with ghost cells, not with other epithelial components.
      Immunoreactivity for phosphothreonine, detected in hard alpha-keratins, also was
      found in transitional, shadow, and ghost cells. The appearance of shadow or ghost
      cells might represent differentiation into hair in these 3 kinds of tumors.

PMID- 15716234
TI  - Fibrosis heterogeneity in nonalcoholic steatohepatitis and hepatitis C virus
      needle core biopsy specimens.
AB  - We examined 46 nonalcoholic steatohepatitis (NASH) and 52 hepatitis C virus (HCV)
      biopsy specimens to determine the magnitude of fibrosis heterogeneity and minimum
      length for accurate fibrosis staging. Three fibrosis scores were recorded: lowest
      regional, highest regional, and most common overall. Mean specimen lengths were
      1.6 and 1.8 cm in NASH and HCV, respectively (P = .283). Mean (highest minus
      lowest) fibrosis heterogeneity scores (highest regional fibrosis - lowest
      regional fibrosis) were 3.7 and 2.0 in NASH and HCV, respectively (P < .001). Of
      36 NASH specimens longer than 1.0 cm, 31 (86%) had the highest regional fibrosis
      in the deepest sampled parenchyma. Shorter specimens were associated
      significantly with greater fibrosis heterogeneity in NASH (coefficient, -1.3; P <
      .001) but not in HCV (P = .901). NASH specimens longer than 1.6 cm had
      significantly lower mean heterogeneity scores than specimens 1.6 cm or shorter
      (1.2 vs 3.4; P = .012). In NASH, fibrosis heterogeneity can be substantial and is
      greater than in HCV, and parenchymal injury, fibrosis, and healing might vary in
      different regions of the liver. The fibrosis stage in patients with NASH might
      not be assessed accurately in short specimens. Individual needle cores should be
      longer than 1.6 cm in NASH for accurate fibrosis staging.

PMID- 15716235
TI  - Nodular fasciitis of the hand: a potential diagnostic pitfall in fine-needle
      aspiration cytopathology.
AB  - Fine-needle aspiration biopsy (FNAB) is applied very uncommonly to soft tissue
      masses and even more infrequently to lesions of the hand. Nodular fasciitis, an
      uncommon pseudosarcomatous lesion of soft tissue, rarely occurs in the hand and,
      because of this, is not often considered in the differential diagnosis of hand
      masses. We report 3 cases (2 men and 1 woman; mean age, 44.3 years) of soft
      tissue masses of the hand, which, after clinical and radiologic evaluation, were
      strongly suspected by an experienced orthopedic oncologist as harboring a soft
      tissue sarcoma. Each patient underwent FNAB, which showed markedly hypercellular
      smears with overlapping, relatively isomorphic spindle cells that were mistaken
      cytologically as possible sarcoma in 2 cases; 1 case was considered probable
      nodular fasciitis. All lesions eventually were diagnosed as nodular fasciitis
      after thorough histologic and immunohistologic evaluation. Nodular fasciitis
      remains a difficult diagnosis by FNAB, particularly when it occurs in locations
      such as the hand.

PMID- 15716236
TI  - Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary
      carcinoids.
AB  - Carcinoids of different organs appear morphologically indistinguishable. We
      studied the usefulness of differential expression of CDX2 and thyroid
      transcription factor-1 (TTF-1) in 78 gastrointestinal and pulmonary carcinoids
      and their metastases (n = 10). CDX2 staining of gastric biopsy specimens with
      neuroendocrine hyperplasia (n = 11) and various gastritides (n = 10) was also
      performed. All ileal (6/6 [100%]), 6 (86%) of 7 appendiceal, 3 (75%) of 4
      duodenal, 1 (50%) of 2 ampullary, 12 (33%) of 18 rectal, 6 (30%) of 20
      pancreatic, and 1 (17%) of 6 gastric carcinoids expressed CDX2 with variable
      intensity; none of the pulmonary carcinoids stained. Of 15 pulmonary carcinoids,
      8 (53%) stained with TTF-1, but none of the gastrointestinal carcinoids did. CDX2
      and TTF-1 staining profiles of primary and metastatic carcinoids were similar.
      CDX2+ gastric endocrine cells had a distribution similar to that of gastrin and
      enterochromaffin cells but not enterochromaffin-like cells. Our results suggest
      that CDX2 and TTF-1 have high specificity for gastrointestinal and pulmonary
      carcinoids, respectively.

PMID- 15716237
TI  - Matrix metalloproteinase expression is related to angiogenesis and histologic
      grade in spindle cell soft tissue neoplasms of the extremities.
AB  - We defined the immunocytochemical expression of matrix metalloproteinases (MMPs)
      and their tissue inhibitors (TIMPs) in benign soft tissue neoplasms,
      fibromatoses, and sarcomas, together with the activity of gelatinase MMPs and
      TIMPs measured by zymography and reverse zymography in a subset of cases. The
      most strongly expressed MMP in all tumors was MMP-1, with weaker expression of
      MMP-10, MMP-11, and MMP-14 in most tumors. Nuclear expression of MMP-1, MMP-8,
      and MMP-13 was an unusual feature. TIMP-2 was expressed in all tumors, with
      stronger expression in fibromatoses than in sarcomas. Fibromatoses and high-grade
      sarcomas showed greater MMP-1 expression than other groups, and endothelial MMP-2
      expression was more extensive in sarcomas. Differences in MMP and TIMP expression
      might be linked to the biologic behavior of soft tissue neoplasms. The activation
      of endothelial MMP-2 linked to widespread MMP-14 expression provides a mechanism
      for sarcomas to modulate their matrix and facilitate angiogenesis.

PMID- 15716238
TI  - Cyclooxygenase 2, p53, beta-catenin, and APC protein expression in gastric
      adenomatous polyps.
AB  - Gastric adenomatous polyps are rare findings in upper gastrointestinal endoscopy;
      however, they are associated strongly with malignant transformation. Few series
      describe the oncogenic characteristics of gastric adenomas. In the present study,
      we immunohisto-chemically assessed the expression of cyclooxygenase (COX)-2, beta
      catenin, p53, and adenomatous polyposis coli (APC) in paraffin-embedded specimens
      of 14 gastric adenomas. Control samples of normal gastric tissue and gastric
      adenocarcinoma also were analyzed. Of the adenomas, 7 demonstrated overexpression
      of COX-2, and all demonstrated nuclear p53 accumulation. Accumulation of beta
      catenin in the nucleus and cytoplasm was detected in 38% (3/8) of specimens. Loss
      of APC staining was observed in 50% (4/8). Similar alterations in oncoprotein
      expression were seen in gastric cancers but not in normal control sections.
      Gastric adenomas display alterations in the expression of COX-2, beta-catenin,
      and APC similar to those seen in adenocarcinomas; however, accumulation of p53
      was significantly more common in adenomas than in cancers.

PMID- 15716239
TI  - Overexpression of glutathione s-transferase alpha in clear cell renal cell
      carcinoma.
AB  - To determine its diagnostic value, we evaluated glutathione S-transferase alpha
      (GST-alpha) expression in a large number of renal cell carcinomas (RCCs). GST
      alpha messenger RNA (mRNA) levels from 70 renal neoplasms were analyzed with
      complementary DNA (cDNA) microarray chips containing 21,632 cDNA clones.
      Furthermore, 348 primary renal tumors and 24 metastatic RCCs were subjected to
      immunohistochemical analysis with a GST-alpha-specific antibody. GST-alpha mRNA
      was elevated significantly (11.4-fold) in a majority of clear cell RCCs (28/43
      [65.1%]; 28/39 [71.8%] with adjustments for informative spots) compared with
      other kidney tumors (1/27 [3.7%]). Strong and diffuse GST-alpha immunoreactivity
      was demonstrated in a majority of clear cell (166/202 [82.2%]; mean intensity,
      2.41) and metastatic clear cell RCCs (17/24 [70.8%]; mean intensity, 2.62). Other
      renal tumor types did not exhibit significant GST-alpha immunoreactivity,
      confirming mRNA results. Through cDNA microarrays and immunohistochemical
      analysis, we demonstrated GST-alpha as a biomarker for clear cell RCCs.

PMID- 15716240
TI  - Factors affecting urinary myoglobin stability in vitro.
AB  - Urine myoglobin concentrations are measured clinically to assess rhabdomyolysis
      and the related risk of renal damage. We studied urine myoglobin concentrations
      in vitro to explore the factors affecting stability. Myoglobin was very unstable
      in urine specimens, especially below pH 6.5, and its immunoreactivity
      deteriorated rapidly with increasing temperatures. The deterioration rate was
      influenced greatly by urine myoglobin concentration, suggesting rate-limiting
      kinetics. Myoglobin in acidic phosphate-buffered saline was significantly more
      stable than in acidic urine, indicating that urinary factors in addition to pH
      are involved in myoglobin instability. These unidentified urinary factors had a
      molecular weight of less than 10 kd. Our results provide additional insight into
      the mechanism involved in the instability of the urine myoglobin concentration.
      Understanding the stability of myoglobin in the preanalytic in vitro phase and
      its potential in vivo instability is essential in assuring the reliability and
      clinical usefulness of urine myoglobin measurements.

PMID- 15716241
TI  - Performance characteristics of four automated natriuretic peptide assays.
AB  - Measurement of circulating B-type natriuretic peptide (BNP) and N-terminal proBNP
      (NT-proBNP) can identify patients with heart failure and guide therapy. The limit
      of detection, linearity, imprecision, method comparison, analytic concordance,
      and reference intervals of the Access 2 BNP (Biosite, San Diego, CA), ADVIA
      Centaur BNP (Bayer Diagnostics, Tarrytown, NY), AxSYM BNP (Abbott Diagnostics,
      Abbott Park, IL), and E170 NT-proBNP (Roche Diagnostics, Indianapolis, IN)
      methods were evaluated. The Triage meter BNP assay (Biosite) was the comparison
      method. Imprecision testing showed total coefficients of variation of 4.1%, 4.4%,
      5.5%, and 0.8% for the Access 2, ADVIA Centaur, AxSYM, and E170, respectively.
      Relative to the Triage meter, method comparison revealed a slope of 0.96 and r =
      0.95, a slope of 0.77 and r = 0.92, a slope of 1.13 and r = 0.94, and a slope of
      8.8 and r = 0.80 for the Access 2, ADVIA Centaur, AxSYM, and E170, respectively.
      Overall analytic concordance values with the Triage meter were 95.9%, 92.9%,
      92.4%, and 84.3% for the Access 2, ADVIA Centaur, AxSYM, and E170, respectively.
      All automated natriuretic peptide methods showed acceptable analytic performance.

PMID- 15716243
TI  - T-cell prolymphocytic leukemia involving extramedullary sites.
AB  - T-cell prolymphocytic leukemia (T-PLL) can involve extramedullary sites, but the
      diagnosis is usually established by examination of blood and bone marrow. As a
      result, the histologic findings at extramedullary sites are poorly documented in
      the literature. We describe 19 extramedullary biopsy specimens from 14 patients
      with T-PLL. Skin (n = 10) was the most common site biopsied. T-PLL surrounded
      dermal blood vessels and appendages (n = 6), diffusely replaced dermis (n = 3),
      or formed a subcutaneous mass (n = 1). Other extramedullary sites included liver
      and lymph nodes (3 each) and spleen, lung, and cecum (1 each). In liver and lymph
      nodes, the neoplasm predominantly involved portal tracts and paracortex,
      respectively. Cytologically, the T-PLL cells were round (n = 16) or Sezary cell
      like (n = 3). Nucleoli were observed in a subset of cells in 8 specimens and were
      prominent in 3 specimens. Immunostaining for T-cell leukemia-1 (TCL-1) was
      positive in specimens from 9 (64%) of 14 patients. We conclude that the
      prolymphocytoid features of T-PLL cells can be difficult to detect in routinely
      stained sections of extramedullary biopsy specimens. TCL-1 expression can aid in
      diagnosis at extramedullary sites.

PMID- 15716242
TI  - Peripheral T-cell lymphoma with a "follicular" pattern and the perifollicular
      sinus phenotype.
AB  - We report a case of peripheral T-cell lymphoma (PTCL) with an exclusively
      "follicular" pattern at one lymph node site and a diffuse pattern at a second
      lymph node site. Molecular studies confirmed the clonal identity of the tumor at
      both sites. In the lymph node showing a follicular pattern, the tumor cells
      appeared to infiltrate follicles where the perifollicular sinuses remained
      patent. The infiltrated follicles retained nonneoplastic B cells and a follicular
      dendritic cell network. By contrast, in the lymph node showing diffuse
      involvement, intranodal sinuses were no longer identifiable and there was no
      evidence of tumor cells infiltrating follicles. The tumor immunophenotype was
      influenced by the pattern: the follicular component was positive and the diffuse
      component was negative for bcl-6 and CD31. We suggest that the follicular growth
      pattern in this case of PTCL arose secondarily to tumor spread via the
      perifollicular sinus.

PMID- 15716244
TI  - Expression of bcl-3 in chronic lymphocytic leukemia correlates with trisomy 12
      and abnormalities of chromosome 19.
AB  - The bcl-3 gene at chromosome 19q13 encodes a member of the IkB family involved in
      regulating the nuclear factor kB pathway. Originally identified by its
      involvement in the t(14:19)(q32;q13), bcl-3 expression recently has been reported
      in 12% of non-Hodgkin lymphomas and 41% of Hodgkin lymphomas. Because the
      t(14;19) is detected most commonly in chronic lymphocytic leukemia (CLL), we
      assessed for bcl-3 expression using immunohistochemical analysis in 72 CLL cases
      with immunophenotypic and cytogenetic data. Of 72 CLL cases, 12 (17%) were bcl
      3+. Expression of bcl-3 correlated with an atypical immunophenotype, defined
      using the World Health Organization scoring system. Expression also correlated
      with trisomy 12 and chromosome 19 abnormalities but was not limited to cases with
      the t(14:19)(q32;q13). Although the mechanism of bcl-3 expression is unclear,
      these results raise the possibility that bcl-3 may be involved in the
      pathogenesis of this subset of tumors and could be a potential target for
      investigational therapies.

PMID- 15716245
TI  - Stereological quantification of nerve fibers immunoreactive to PGP 9.5, NPY, and
      VIP in rat prostate during postnatal development.
AB  - This work was undertaken to study prostate innervation during the postnatal
      development of rats. It deals with the quantification of nervous fibers
      throughout all the regions of the rat prostate during the postnatal development
      using a general marker for nervous tissue, protein gene product 9.5, and 2
      neuropeptides (NPY and VIP). Forty male Wistar rats (prepubertals, pubertals,
      young, and aged adults) were studied for immunohistochemistry of protein gene
      product (PGP 9.5), neuropeptide Y (NPY), and vasoactive intestinal polypeptide
      (VIP). They were also evaluated for length density of nerve fibers (L(V) PGP 9.5,
      L(V) NPY, L(V) VIP). Nerve fibers immunoreactive to the 3 antigens studied were
      detected in all the groups and in all the prostate zones. Periductal L(V) NPY
      evidenced a significant increase in the pubertal group, maintained throughout
      adult life. Periductal L(V) VIP showed a significant increase in young adults.
      The length densities of VIP and NPY fibers were significantly higher in
      periductal and ampular locations in comparison with dorsal and ventral sites. It
      can be concluded that the relative amount of nerve fibers in rat prostate,
      detected by PGP 9.5, does not change during postnatal development. There were
      significant changes in NPY and VIP fibers, showing an increase in periurethral
      ducts at puberty. The abundance of peptidergic innervation around the excretory
      ducts is related to their contractility. The development of innervation of
      periurethral ducts is regulated by androgens.

PMID- 15716246
TI  - Patients with recurrent falls attending Accident & Emergency benefit from
      multifactorial intervention--a randomised controlled trial.
AB  - OBJECTIVES: To determine the effectiveness of multifactorial intervention to
      prevent falls in cognitively intact older persons with recurrent falls. DESIGN:
      Randomised controlled trial of multifactorial (medical, physiotherapy and
      occupational therapy) post-fall assessment and intervention compared with
      conventional care. SETTING: Accident & Emergency departments in a university
      teaching hospital and associated district general hospital. SUBJECTS: 313
      cognitively intact men and women aged over 65 years presenting to Accident &
      Emergency with a fall or fall-related injury and at least one additional fall in
      the preceding year; 159 randomised to assessment and intervention and 154 to
      conventional care. OUTCOME MEASURES: primary outcome was the number of falls and
      fallers in 1 year after recruitment. Secondary outcomes included injury rates,
      fall-related hospital admissions, mortality and fear of falling. RESULTS: There
      were 36% fewer falls in the intervention group (relative risk 0.64, 95%
      confidence interval 0.46-0.90). The proportion of subjects continuing to fall
      (65% (94/144) compared with 68% (102/149) relative risk 0.95, 95% confidence
      interval 0.81-1.12), and the number of fall-related attendances and hospital
      admissions was not different between groups. Duration of hospital admission was
      reduced (mean difference admission duration 3.6 days, 95% confidence interval 0.1
      7.6) and falls efficacy was better in the intervention group (mean difference in
      Activities Specific Balance Confidence Score of 7.5, 95% confidence interval 0.72
      14.2). CONCLUSION: Multifactorial intervention is effective at reducing the fall
      burden in cognitively intact older persons with recurrent falls attending
      Accident & Emergency, but does not reduce the proportion of subjects still
      falling.

PMID- 15716248
TI  - Understanding the anterior cruciate ligament: rhythm and algorithm.

PMID- 15716249
TI  - Prospective trial of a treatment algorithm for the management of the anterior
      cruciate ligament-injured knee.
AB  - BACKGROUND: Specific guidelines for operative versus nonoperative management of
      anterior cruciate ligament injuries do not yet exist. HYPOTHESIS: Surgical risk
      factors can be used to indicate whether reconstruction or conservative management
      is best for an individual patient. STUDY DESIGN: Prospective nonrandomized
      controlled clinical trial; Level of evidence, 2. METHODS: Patients were
      classified as high, moderate, or low risk using preinjury sports participation
      and knee laxity measurements. Early anterior cruciate ligament reconstruction
      (within 3 months of injury) was recommended to high-risk patients and
      conservative care to low-risk patients. It was recommended that moderate-risk
      patients have either early reconstruction or conservative care, according to the
      day of presentation. Assessment of subjective outcomes, activity, physical
      measurements, and radiographs was performed at mean follow-up of 6.6 years.
      RESULTS: Early phase conservative management resulted in more late phase meniscus
      surgery than did early phase reconstruction at all risk levels (high risk, 25% vs
      6.5%; moderate risk, 37% vs 7.7%, P = .01; low risk, 16% vs 0%). Early- and late
      reconstruction patients' Tegner scores increased from presurgery to follow-up (P
      < .001) but did not return to preinjury levels. Early-reconstruction patients had
      higher rates of degenerative change on radiographs than did nonreconstruction
      patients (P < .05). CONCLUSIONS: Early phase reconstruction reduced late phase
      knee laxity, risk of symptomatic instability, and the risk of late meniscus tear
      and surgery. Moderate- and high-risk patients had similar rates of late phase
      injury and surgery. Reconstruction did not prevent the appearance of late
      degenerative changes on radiographs. Relationship between bone contusion on
      initial magnetic resonance images and the finding of degenerative changes on
      follow-up radiographs were not detected. The treatment algorithm used in this
      study was effective in predicting risk of late phase knee surgery.

PMID- 15716250
TI  - Rehabilitation after anterior cruciate ligament reconstruction: a prospective,
      randomized, double-blind comparison of programs administered over 2 different
      time intervals.
AB  - BACKGROUND: There are adverse effects associated with immobilization of the knee
      after anterior cruciate ligament reconstruction, yet very little is known about
      how much activity will promote adequate rehabilitation without permanently
      elongating the graft, producing graft failure, or creating damage to articular
      cartilage. HYPOTHESIS: Rehabilitation with either an accelerated or
      nonaccelerated program produces no difference in anterior-posterior knee laxity,
      clinical assessment, patient satisfaction, functional performance, and the
      synovial fluid biomarkers of articular cartilage metabolism. STUDY DESIGN:
      Randomized controlled clinical trial; Level of evidence, 1. METHODS: Twenty-five
      patients who tore their anterior cruciate ligament were enrolled and underwent
      anterior cruciate ligament reconstruction. Patients were randomized to
      accelerated rehabilitation or nonaccelerated rehabilitation. At the time of
      surgery and 3, 6, 12, and 24 months later, measurements of anterior-posterior
      knee laxity, clinical assessment, patient satisfaction, functional performance,
      and cartilage metabolism were completed. RESULTS: At the 2-year follow-up, there
      was no difference in the increase of anterior knee laxity relative to the
      baseline values that were obtained immediately after surgery between the 2 groups
      (2.2-mm vs 1.8-mm increase relative to the normal knee). The groups were similar
      in terms of clinical assessment, patient satisfaction, activity level, function,
      and response of the bio-markers. After 1 year of healing, synthesis of collagen
      and turnover of aggrecan remained elevated in both groups. CONCLUSION: Anterior
      cruciate ligament reconstruction with a bone-patellar tendon-bone graft followed
      by either accelerated or nonaccelerated rehabilitation produces the same increase
      of anterior knee laxity. Both programs had the same effect in terms of clinical
      assessment, patient satisfaction, functional performance, and the biomarkers of
      articular cartilage metabolism. There is concern that the cartilage biomarkers
      remained elevated for an extended period.

PMID- 15716251
TI  - Biomechanical analysis of a combined double-bundle posterior cruciate ligament
      and posterolateral corner reconstruction.
AB  - BACKGROUND: Failure to address both components of a combined posterior cruciate
      ligament and posterolateral corner injury has been implicated as a reason for
      abnormal biomechanics and inferior clinical results. HYPOTHESIS: Combined double
      bundle posterior cruciate ligament and posterolateral corner reconstruction
      restores the kinematics and in situ forces of the intact knee ligaments. STUDY
      DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen human cadaveric
      knees were tested using a robotic testing system through sequential cutting and
      reconstructing of the posterior cruciate ligament and posterolateral corner. The
      knees were subjected to a 134-N posterior tibial load and a 5-N.m external tibial
      torque at multiple flexion angles. The double-bundle posterior cruciate ligament
      reconstruction was performed using Achilles and semitendinosus tendons. The
      posterolateral corner reconstruction consisted of reattaching the popliteus
      tendon to its femoral origin and reconstructing the popliteofibular ligament with
      a gracilis tendon. RESULTS: Under the posterior load, the combined reconstruction
      reduced posterior translation to within 1.2 +/- 1.5 mm of the intact knee. The in
      situ forces in the posterior cruciate ligament grafts were significantly less
      than those in the native posterior cruciate ligament at all angles except full
      extension. Conversely, the forces in the posterolateral corner grafts were
      significantly higher than those in the native structures at all angles. Under the
      external torque with the combined reconstruction, external rotation as well as in
      situ forces in the posterior cruciate ligament and posterolateral corner grafts
      were not different from the intact knee. CONCLUSIONS: A combined posterior
      cruciate ligament and posterolateral corner reconstruction can restore intact
      knee kinematics at time zero. In situ forces in the intact posterior cruciate
      ligament and posterolateral corner were not reproduced by the reconstruction;
      however, the posterolateral corner reconstruction reduced the loads experienced
      by the posterior cruciate ligament grafts. CLINICAL RELEVANCE: By addressing both
      structures of this combined injury, this technique restores native kinematics
      under the applied loads at fixed flexion angles and demonstrates load sharing
      among the grafts creating a potentially protective effect against early failure
      of the posterior cruciate ligament grafts but with increased force in the
      posterolateral corner construct.

PMID- 15716252
TI  - Injuries among competitive snowboarders at the national elite level.
AB  - BACKGROUND: Little is known about injury risk or the pattern of injuries among
      competitive snowboarders. PURPOSE: To describe the incidence and pattern of
      injuries among female and male snowboard athletes at the highest national level.
      STUDY DESIGN: Descriptive epidemiology study. METHODS: This study consists of 2
      parts: prospective registration of injuries at snowboarding national cup events
      and the national championships during the 2002 season, as well as a retrospective
      interview of the participants during the national championships in March 2002.
      All injuries that resulted in missed participation were recorded. Exposure was
      recorded as the number of runs in all disciplines. RESULTS: In the prospective
      study, the competition incidence was 4.0 +/- 0.7 injuries per 1000 runs (n = 32
      injuries). Back (22%), knee (16%), and hand/wrist injuries (9%) were the most
      common. The incidence for the different disciplines was 14.2 +/- 5.3 per 1000
      runs for big jump, 6.1 +/- 1.8 for snowboardcross, 3.1 +/- 0.9 for halfpipe, and
      1.9 +/- 1.9 for giant slalom. The retrospective interview (n = 163 athletes, 83%
      response) revealed 84 acute time-loss injuries during the season; knee (16%),
      back (13%), head (13%), and hand/wrist injuries (12%) were the 4 most common
      injury types. The overall competition incidence was 3.4 +/- 0.6 injuries per 1000
      runs (6.6 +/- 3.0 for big jump, 5.8 +/- 1.7 for snowboardcross, 2.1 +/- 0.7 for
      halfpipe, and 6.6 +/- 4.7 for giant slalom). No injury was recorded in parallel
      slalom in either study. CONCLUSION: The incidence of injuries is high among
      competitive snowboarders at the elite national level. The injury pattern is
      different from the panorama seen among less experienced athletes, with fewer
      wrist injuries and more knee injuries.

PMID- 15716253
TI  - Opening wedge tibial osteotomy: the 3-triangle method to correct axial alignment
      and tibial slope.
AB  - BACKGROUND: Although a change in tibial slope may occur during a medial opening
      wedge osteotomy, calculations have not been defined to address this problem. The
      authors investigated geometric factors important to correct axial alignment and
      tibial slope during osteotomy. PURPOSE: To calculate, through 3-dimensional
      analysis of the proximal tibia, how the angle of the opening wedge along the
      anteromedial tibial cortex influences the tibial slope (sagittal plane) and
      valgus correction (coronal plane) during osteotomy, and to analyze the different
      radiographic methods reported in the literature to measure medial and lateral
      tibial slope. The authors postulated that differences in reported normal values
      of tibial slope in the sagittal plane were technique dependent. STUDY DESIGN:
      Descriptive laboratory study. METHODS: The proximal anteromedial tibial cortex
      obliquity on magnetic resonance imaging was measured in 35 knees. Serial computed
      tomography images of the proximal tibia were digitized, allowing a series of
      virtual opening wedge osteotomies to be performed. Algebraic calculations defined
      the effect of an opening wedge osteotomy on the anteromedial tibial cortex
      opening wedge angle, sagittal tibial slope angle, and coronal valgus alignment.
      RESULTS: The anteromedial tibial cortex oblique angle at the medial osteotomy
      site was 45 degrees +/- 6 degrees and determined, along with the degrees of
      valgus correction, the degrees of the opening wedge angle in the oblique plane.
      The anterior osteotomy gap at the tibial tubercle was generally one half of the
      posteromedial gap to maintain the normal sagittal tibial slope. Every millimeter
      of gap error at the tibial tubercle resulted in approximately 2 degrees of change
      in the tibial slope. The width of the buttress plate along the anteromedial
      tibial cortex was 2 to 3 mm less than the computed coronal valgus posteromedial
      osteotomy gap to achieve tibiofemoral valgus correction. CONCLUSIONS: A series of
      measurements preoperatively and intraoperatively are required to obtain the
      desired correction of tibial slope and valgus alignment.

PMID- 15716254
TI  - Cyclic testing of flexible all-inside meniscus suture anchors: biomechanical
      analysis.
AB  - BACKGROUND: Flexible meniscus repair devices are designed to combine the benefits
      of rigid all-inside meniscus anchors with the biomechanical properties of
      sutures. HYPOTHESIS: Stiffness and pull-out strength of flexible all-inside
      suture anchors and conventional sutures under cyclic loading conditions will be
      comparable. STUDY DESIGN: Controlled laboratory study. METHODS: In 50 fresh
      frozen bovine menisci, artificial meniscus lesions were repaired with different
      meniscus fixation techniques: horizontal and vertical FasT-Fix, RapidLoc, and
      horizontal and vertical 2-0 Ethibond sutures. The specimens were cycled 1000
      times between 5 and 20 N and then loaded to failure. RESULTS: All devices
      survived the cyclic loading protocol. There was no significant difference in the
      displacement between all repair techniques tested (horizontal FasT-Fix, 6.23 mm;
      vertical FasT-Fix, 5.34 mm; RapidLoc, 6.84 mm; horizontal 2-0 Ethibond, 6.03 mm;
      vertical 2-0 Ethibond, 5.61 mm (P > .05). Vertical and horizontal FasT-Fix suture
      anchors had a significantly higher stiffness and pull-out strength (94.1 N and
      80.8 N, respectively) than did horizontal sutures (50.2 N) and RapidLoc devices
      (30.3 N) (P > .05). CONCLUSIONS: In this study, flexible all-inside meniscus
      anchors (FasT-Fix) had higher pull-out strength than did conventional vertical
      suture techniques. Biomechanical characteristics of the flexible RapidLoc are
      comparable to those of horizontal sutures. CLINICAL RELEVANCE: Flexible all
      inside meniscus repair devices are an alternative to conventional suture
      techniques.

PMID- 15716255
TI  - Stress distribution in the superior labrum during throwing motion.
AB  - BACKGROUND: Superior labrum anterior posterior lesions are common among athletes
      participating in overhead throwing sports. One described mechanism of injury is
      application of high local stress via repetitive loading of the long head of the
      biceps tendon attached to the superior labrum; however, the stress environment
      within the labrum has not been investigated to date. HYPOTHESIS: Biceps origin
      locations and throwing phases determine the stress distributions causing lesions
      of the superior labrum within the labrum itself. STUDY DESIGN: Descriptive
      laboratory study. METHODS: Three-dimensional finite element models of the labrum
      glenoid complex with anterior, central, and posterior biceps origins were
      developed at 4 orientations to simulate the phases of pitching: early cocking,
      late cocking, acceleration, and deceleration. RESULTS: The stress magnitudes at
      the labrum glenoid interface for the deceleration phase were highest for all
      biceps origins. Anatomical variations of the biceps insertion affected the stress
      only during the deceleration phase. Both the biceps origin and throwing phase
      influenced the location of high stress. CONCLUSION: Deceleration could be the
      throwing phase that causes tearing at the superior labrum. This finding provides
      further understanding for localizing the possible initiation of superior labrum
      anterior posterior lesions.

PMID- 15716256
TI  - Quadriceps weakness, atrophy, and activation failure in predicted noncopers after
      anterior cruciate ligament injury.
AB  - BACKGROUND: Quadriceps weakness is common after anterior cruciate ligament
      injury, especially in those who do not compensate well for the injury
      ("noncopers"). Both atrophy and activation failure have been demonstrated in this
      population but have not been directly related to quadriceps weakness. HYPOTHESES:
      (1) Quadriceps strength, volumes, and cross-sectional areas of the noncopers
      would be smaller than those of the contralateral muscles, whereas other muscles
      would not demonstrate atrophy. (2) Quadriceps muscle activation deficits would be
      observed. (3) Atrophy and activation failure would account for the quadriceps
      weakness in these patients. STUDY DESIGN: Cross-sectional study, Level of
      evidence, 3. METHODS: Seventeen noncopers with isolated anterior cruciate
      ligament injury underwent burst-superimposition strength and activation testing
      of the quadriceps and magnetic resonance imaging of 12 muscles an average of 2
      months after injury. Morphological characteristics was described by digitally
      reconstructing each muscle from the axial images and calculating muscle volume
      and peak cross-sectional area. RESULTS: The quadriceps muscles of the anterior
      cruciate ligament-deficient limb were significantly weaker (average 25%) than
      those of the uninjured side; activation failure (8%-10%) was observed for the
      quadriceps muscles of both limbs. The total quadriceps, vastus lateralis, and
      vastus intermedius volume and cross-sectional area were significantly smaller in
      the anterior cruciate ligament-deficient limb. There was no significant atrophy
      of any other muscle or muscle group. Atrophy and activation failure explained
      more than 60% of the variance in quadriceps weakness (P = .004). CONCLUSION: The
      quadriceps femoris weakens soon after acute anterior cruciate ligament injury.
      Activation deficits and atrophy occur and affect quadriceps strength.
      Rehabilitation techniques that address activation deficits as well as atrophy may
      be necessary to restore quadriceps strength.

PMID- 15716257
TI  - Arthroscopic cartilage indentation and cartilage lesions of anterior cruciate
      ligament-deficient knees.
AB  - BACKGROUND: The anterior cruciate ligament-deficient knee is prone to
      osteoarthritis and meniscus lesions. Very little, however, is known about the
      biomechanical properties of articular cartilage in anterior cruciate ligament
      deficient knees. PURPOSE: To evaluate biomechanical and macroscopical cartilage
      changes in the knee joint with respect to the time after anterior cruciate
      ligament rupture. HYPOTHESIS: Chronic anterior cruciate ligament deficiency
      induces cartilage softening. STUDY DESIGN: Cross-sectional study; Level of
      evidence, 3. METHODS: Cartilage stiffness of 50 patients undergoing anterior
      cruciate ligament reconstructive surgery because of symptomatic knee instability
      after chronic anterior cruciate ligament rupture was measured with an
      arthroscopic indenter device, and the number and size of cartilage lesions were
      evaluated. RESULTS: The cartilage stiffness did not correlate with time from
      trauma to surgery (r = 0.002, P = .99), but the number of cartilage lesions in
      the knee increased when the time from the initial trauma to reconstructive
      surgery increased (r = 0.356, P = .011). Indentation values measured on healthy
      looking cartilage on damaged joint surfaces were lower than the values measured
      on healthy joint surfaces (P < .01 on lateral femoral condyle and on tibial
      plateaus). CONCLUSIONS: The number of cartilage lesions increases with increased
      time after initial trauma. The arthroscopic indenter device is able to detect
      cartilage softening as the early mechanical sign of degradation not yet visible
      to the eye.

PMID- 15716258
TI  - Intrinsic risk factors for inversion ankle sprains in male subjects: a
      prospective study.
AB  - BACKGROUND: Many variables have been retrospectively associated with ankle
      sprains. However, very little is known about factors predisposing people to these
      injuries. HYPOTHESIS: Measurable intrinsic factors might predispose male athletes
      to ankle sprains. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A
      total of 241 male physical education students were evaluated for possible
      intrinsic risk factors for inversion sprains at the beginning of their academic
      study. The evaluated intrinsic risk factors included anthropometrical
      characteristics, functional motor performances, ankle joint position sense,
      isokinetic ankle muscle strength, lower leg alignment characteristics, postural
      control, and muscle reaction time during a sudden inversion perturbation.
      Subjects were followed prospectively for 1 to 3 years. RESULTS: A total of 44
      (18%) of the 241 male subjects sustained an inversion sprain; 4 sprained both
      ankles. Cox regression analysis revealed that male subjects with slower running
      speed, less cardiorespiratory endurance, less balance, decreased dorsiflexion
      muscle strength, decreased dorsiflexion range of motion, less coordination, and
      faster reaction of the tibialis anterior and gastrocnemius muscles are at greater
      risk of ankle sprains. CONCLUSION: Based on our findings, it is suggested that
      running speed, cardiorespiratory endurance, balance, dorsiflexion strength,
      coordination, muscle reaction, and dorsiflexion range of motion at the ankle are
      associated with the risk of ankle inversion sprains in male subjects.

PMID- 15716259
TI  - De Quervain disease in volleyball players.
AB  - BACKGROUND: Chronic inflammatory tendon diseases in athletes are frequent, and
      they often result from modifications in normal kinematics of a tendon associated
      with a patient's anatomical determinants. De Quervain stenosing tenosynovitis is
      an inflammatory disease of tendons of the first dorsal compartment of the wrist.
      There is no literature about this disease concerning professional volleyball
      players. HYPOTHESIS: Limited, multiple trauma on the dorsal radial portion of the
      wrist, associated with long training times, can be involved in the pathogenetic
      process of de Quervain disease in professional volleyball players. STUDY DESIGN:
      Case series; Level of evidence, 4. MATERIALS AND METHODS: The authors studied 45
      consecutively enrolled volleyball players (27 professional, 18 nonprofessional)
      satisfying clinical criteria for the diagnosis of de Quervain stenosing
      tenosynovitis. All patients were evaluated by questionnaire and physical
      examination. They were divided into group A (mild) and group B (severe) based on
      the severity of the symptoms and physical findings; they were followed for a mean
      of 37 months. RESULTS: Total training quantity (mean weekly training time
      multiplied by mean sports activity duration) in group A was 74, whereas it was
      155 in group B (P < .01). No neuropathies were found in group A, whereas they
      were found in 3 patients in group B. Fifty percent of surgical patients had a
      longitudinal fibrous septum, whereas 54% showed multiple tendon sheaths making up
      the abductor pollicis longus tendon. CONCLUSIONS: This study shows that increased
      training time and consequent microtrauma associated with professional volleyball
      activity can increase the likelihood of de Quervain disease.

PMID- 15716260
TI  - Risk factors for injury in subelite rugby league players.
AB  - BACKGROUND: Although player fatigue and playing intensity have been suggested to
      contribute to injuries in rugby league players, no study has confirmed if the
      level of physical fitness is a risk factor for injury in rugby league players.
      The aim of this study was to identify risk factors for injury in subelite rugby
      league players. HYPOTHESIS: Low physical fitness levels are risk factors for
      injury in subelite rugby league players. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: One hundred fifty-three players from a subelite rugby
      league club underwent preseason measurements of muscular power (vertical jump),
      speed (10- and 40-m sprint), and maximal aerobic power (multistage fitness test)
      over 4 competitive seasons. All injuries sustained by players were prospectively
      recorded over the 4 competitive seasons. RESULTS: The risk of injury was greater
      in players with low 10- and 40-m speed. Players with a low maximal aerobic power
      had a greater risk of sustaining a contact injury. In addition, players who
      completed less than 18 weeks of training before sustaining their initial injuries
      were at greater risk of sustaining a subsequent injury. CONCLUSIONS: Subelite
      rugby league players with low speed and maximal aerobic power are at an increased
      risk of injury. In addition, players who complete less than 18 weeks of training
      before sustaining an initial injury are at greater risk of sustaining a
      subsequent injury. These findings highlight the importance of speed and endurance
      training to reduce the incidence of injury in subelite rugby league players.

PMID- 15716261
TI  - A radiographic investigation to determine the safety of suture anchor systems for
      pediatric modified Brostrom ankle ligament reconstruction.
AB  - BACKGROUND: The modified Brostrom ligament reconstruction using anchor sutures
      has been performed in adults with clinical success; however, the safety
      parameters for the use of suture anchors in adolescent lateral ankle ligament
      reconstruction have not been established. PURPOSE: To perform a radiographic
      analysis comparing the depth of penetration of suture anchors in adult ankle
      ligament reconstruction with the average distance of the physis from the tip of
      the fibula in adolescents. STUDY DESIGN: Cross-sectional study, Level of
      evidence, 4. METHODS: Forty postoperative ankle radiographs of adult patients who
      had a modified Brostrom procedure were compared with 40 normal adolescent ankle
      radiographs. In the adult group, the distance of the suture anchor penetration
      from the distal tip of the fibula was measured; in the adolescent group, the
      distance of the physis from the distal tip of the fibula was measured. RESULTS:
      The mean depth of the suture anchors was 17 mm (range, 14-21 mm) from the tip of
      the fibula in the adult group, and the mean distance of the growth plate was 23
      mm (range, 18-29 mm) in the adolescent group. Eight radiographs from the
      adolescent group (20%) had a physis measurement of <22 mm on the anteroposterior
      or mortise view. CONCLUSIONS: Using careful preoperative planning and
      intraoperative technique, it is possible to safely perform lateral ankle ligament
      repair in the skeletally immature patient using suture anchors.

PMID- 15716262
TI  - Lateral ulnar collateral ligament reconstruction in a skeletally immature
      patient.

PMID- 15716263
TI  - Cartilage restoration, part 2: techniques, outcomes, and future directions.
AB  - In part 1 of this 2-part Current Concepts article, the authors reviewed the basic
      science of normal articular and meniscal cartilage and its response to injury.
      They reviewed the historical perspectives and basic science behind these various
      methods and presented a rationale for patient evaluation, treatment selection,
      and timing. In part 2, the authors review the specific indications for the
      treatment of chondral injuries and describe the techniques and outcomes of the
      various treatment options, including palliative, reparative, and restorative
      procedures. In addition, they will examine specific complex clinical scenarios
      emphasizing treatment options of comorbid conditions including ligament
      instability, meniscal deficiency, and malalignment. A limited review of the
      application of these techniques in joints other than the knee will also be
      presented. A conceptual algorithm is developed to assist in clinical decision
      making.

PMID- 15716264
TI  - Effectiveness of extracorporeal shock wave therapy in the management of tennis
      elbow.

PMID- 15716265
TI  - Incidence and risk factors in the development of medial tibial stress syndrome
      among naval recruits.

PMID- 15716266
TI  - The putidaredoxin reductase-putidaredoxin electron transfer complex: theoretical
      and experimental studies.
AB  - Interaction and electron transfer between putidaredoxin reductase (Pdr) and
      putidaredoxin (Pdx) from Pseudomonas putida was studied by molecular modeling,
      mutagenesis, and stopped flow techniques. Based on the crystal structures of Pdr
      and Pdx, a complex between the proteins was generated using computer graphics
      methods. In the model, Pdx is docked above the isoalloxazine ring of FAD of Pdr
      with the distance between the flavin and [2Fe-2S] of 14.6 A. This mode of
      interaction allows Pdx to easily adjust and optimize orientation of its cofactor
      relative to Pdr. The key residues of Pdx located at the center, Asp(38) and
      Trp(106), and at the edge of the protein-protein interface, Tyr(33) and Arg(66),
      were mutated to test the Pdr-Pdx computer model. The Y33F, Y33A, D38N, D38A,
      R66A, R66E, W106F, W106A, and Delta106 mutations did not affect assembly of the
      [2Fe-2S] cluster and resulted in a marginal change in the redox potential of Pdx.
      The electron-accepting ability of Delta106 Pdx was similar to that of the wild
      type protein, whereas electron transfer rates from Pdr to other mutants were
      diminished to various degrees with the smallest and largest effects on the
      kinetic parameters of the Pdr-to-Pdx electron transfer reaction caused by the
      Trp(106) and Tyr(33)/Arg(66) substitutions, respectively. Compared with wild-type
      Pdx, the binding affinity of all studied mutants to Pdr was significantly higher.
      Experimental results were in agreement with theoretical predictions and suggest
      that: (i) Pdr-Pdx complex formation is mainly driven by steric complementarity,
      (ii) bulky side chains of Tyr(33), Arg(66), and Trp(106) prevent tight binding of
      oxidized Pdx and facilitate dissociation of the reduced iron-sulfur protein from
      Pdr, and (iii) transfer of an electron from FAD to [2Fe-2S] can occur with
      various orientations between the cofactors through multiple electron transfer
      pathways that do not involve Trp(106) but are likely to include Asp(38) and
      Cys(39).

PMID- 15716267
TI  - A dominant negative peroxisome proliferator-activated receptor-gamma knock-in
      mouse exhibits features of the metabolic syndrome.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the
      nuclear hormone receptor family, is a master regulator of adipogenesis. Humans
      with dominant negative PPARgamma mutations have features of the metabolic
      syndrome (severe insulin resistance, dyslipidemia, and hypertension). We created
      a knock-in mouse model containing a potent dominant negative PPARgamma L466A
      mutation, shown previously to inhibit wild-type PPARgamma action in vitro.
      Homozygous PPARgamma L466A knock-in mice die in utero. Heterozygous PPARgamma
      L466A knock-in (PPARKI) mice exhibit hypoplastic adipocytes, hypoadiponectinemia,
      increased serum-free fatty acids, and hepatic steatosis. When subjected to high
      fat diet feeding, PPARKI mice gain significantly less weight than controls.
      Hyperinsulinemic-euglycemic clamp studies in PPARKI mice revealed insulin
      resistance and reduced glucose uptake into skeletal muscle. Female PPARKI mice
      exhibit hypertension independent of diet. The PPARKI mouse provides a novel model
      for studying the relationship between impaired PPARgamma function and the
      metabolic syndrome.

PMID- 15716268
TI  - SIRT1 functionally interacts with the metabolic regulator and transcriptional
      coactivator PGC-1{alpha}.
AB  - In lower organisms, increased expression of the NAD-dependent deacetylase Sir2
      augments lifespan. The mechanism through which this life extension is mediated
      remains incompletely understood. Here we have examined the cellular effects of
      overexpression of SIRT1, the closest mammalian ortholog of Sir2. In PC12 cells,
      increased expression of the NAD-dependent deacetylase SIRT1 reduces cellular
      oxygen consumption by approximately 25%. We further demonstrate that SIRT1
      expression can alter the transcriptional activity of the mitochondrial biogenesis
      coactivator PGC-1alpha. In addition, SIRT1 and PGC-1alpha directly interact and
      can be co-immunoprecipitated as a molecular complex. A single amino acid mutation
      in the putative ADP-ribosyltransferase domain of SIRT1 inhibits the interaction
      of SIRT1 with PGC-1alpha but does not effect the interaction of SIRT1 with either
      p53 or Foxo3a. We further show that PGC-1alpha is acetylated in vivo. This
      acetylation is augmented by treatment with the SIRT1 inhibitor nicotinamide or by
      expression of the transcriptional coactivator p300. Finally we demonstrate that
      SIRT1 catalyzes PGC-1alpha deacetylation both in vitro and in vivo. These results
      provide a direct link between the sirtuins, a family of proteins linked to
      lifespan determination and PGC-1alpha, a coactivator that regulates cellular
      metabolism.

PMID- 15716269
TI  - Hyperactive antifreeze protein from winter flounder is a very long rod-like dimer
      of alpha-helices.
AB  - The winter flounder (Pseudopleuronectes americanus) produces short, monomeric
      alpha-helical antifreeze proteins (type I AFP), which adsorb to and inhibit the
      growth of ice crystals. These proteins alone are not sufficiently active to
      protect this fish against freezing at -1.9 degrees C, the freezing point of
      seawater. We have recently isolated a hyperactive antifreeze protein from the
      plasma of the flounder with activity 10-100-fold higher than type I AFP. It is
      comparable in activity to the AFPs produced by insects, and is capable of
      conferring freeze resistance to the flounder. This novel AFP has a molecular mass
      of 16,683 Da and a remarkable amino acid composition that is >60% alanine. CD
      spectra indicate that the protein is almost entirely alpha-helical at 4 degrees C
      but partially denatures at 20 degrees C, resulting in a species with a moderately
      reduced helix content that is stable at up to 50 degrees C. This transformation
      correlates with irreversible loss of activity. Analytical ultracentrifugation
      (sedimentation velocity and equilibrium) indicates that the predominant species
      in solution is dimeric (molecular weight, 32,275). Size-exclusion chromatography
      reveals a 2-fold higher apparent molecular weight suggesting that this molecule
      has an unusually large Stokes radius. The axial ratio of the dimer calculated
      from the sedimentation velocity data is 18:1, confirming that this protein has an
      extraordinarily long, rod-like structure, consistent with a novel dimeric alpha
      helical arrangement. The structural model that best fits these data is one in
      which the approximately 195 amino acids of each monomer form one approximately
      290-A long alpha-helix and associate via a unique dimerization motif that is
      distinct from that of the leucine zipper and any other coiled-coil.

PMID- 15716270
TI  - Identification and functional analysis of 20 Box H/ACA small nucleolar RNAs
      (snoRNAs) from Schizosaccharomyces pombe.
AB  - Considering all small nucleolar RNAs (snoRNAs) enriched in the nucleolus, we
      generated a specialized cDNA library of small nuclear RNAs from
      Schizosaccharomyces pombe and isolated, for the first time, 20 novel box H/ACA
      snoRNAs. Thirteen of these were characterized as novel guides that were predicted
      to direct 19 pseudouridylations in 18 S and 25 S rRNAs. The remaining seven
      snoRNAs were considered as orphan guides that lack sequence complementarity to
      either rRNAs or snRNAs. We have experimentally demonstrated the function of the
      10 novel snoRNAs by gene deletion in the fission yeast. The snoRNAs were shown to
      be dispensable for the viability of S. pombe, although an impact of snR94
      depletion on yeast growth, especially at 23 degrees C, was revealed. A total of
      30 pseudouridylation sites were precisely mapped in the S. pombe rRNAs, showing a
      distinctive pseudouridylation pattern in the budding yeast. Interestingly, the
      absence of pseudouridylation on U2347 in S. pombe 25 S rRNA pointed out a
      critical role for Psi2345 in conferring a growth advantage for yeast. In contrast
      to the intron-encoded box C/D sno-RNAs in yeast, all box H/ACA snoRNAs appeared
      to be transcribed independently from intergenic regions between two protein
      coding genes, except for snR35, which was nested in an open reading frame
      encoding for a hypothetical protein, although expressed from the opposite strand.
      Remarkably, snR90 was cotranscribed with an intron-encoded box C/D snoRNA, and
      this is the first demonstration of a non-coding RNA gene that encodes two
      different types of snoRNAs by its exon and intron. A detailed comparison of the
      S. pombe snoRNAs, with their functional homologues in diverse organisms, suggests
      a mechanism by which the snoRNAs have evolved in coordination with rRNAs to
      preserve the post-transcriptional modification sites among distant eukaryotes.

PMID- 15716271
TI  - Crystal structure of a PhoU protein homologue: a new class of metalloprotein
      containing multinuclear iron clusters.
AB  - PhoU proteins are known to play a role in the regulation of phosphate uptake. In
      Thermotoga maritima, two PhoU homologues have been identified bioinformatically.
      Here we report the crystal structure of one of the PhoU homologues at 2.0 A
      resolution. The structure of the PhoU protein homologue contains a highly
      symmetric new structural fold composed of two repeats of a three-helix bundle.
      The structure unexpectedly revealed a trinuclear and a tetranuclear iron cluster
      that were found to be bound on the surface. Each of the two multinuclear iron
      clusters is coordinated by a conserved E(D)XXXD motif pair. Our structure reveals
      a new class of metalloprotein containing multinuclear iron clusters. The possible
      functional implication based on the structure are discussed.

PMID- 15716272
TI  - Structural basis for the cell-specific activities of the NGFI-B and the Nurr1
      ligand-binding domain.
AB  - NGFI-B is a ligand-independent orphan nuclear receptor of the NR4A subfamily that
      displays important functional differences with its homolog Nurr1. In particular,
      the NGFI-B ligand-binding domain (LBD) exhibits only modest activity in cell
      lines in which the Nurr1 LBD strongly activates transcription. To gain insight
      into the structural basis for the distinct activation potentials, we determined
      the crystal structure of the NGFI-B LBD at 2.4-angstroms resolution.
      Superimposition with the Nurr1 LBD revealed a significant shift of the position
      of helix 12, potentially caused by conservative amino acids exchanges in helix 3
      or helix 12. Replacement of the helix 11-12 region of Nurr1 with that of NGFI-B
      dramatically reduces the transcriptional activity of the Nurr1 LBD. Similarly,
      mutation of Met414 in helix 3 to leucine or of Leu591 in helix 12 to isoleucine
      (the corresponding residues found in NGFI-B) significantly affects Nurr1
      transactivation. In comparison, swapping the helix 11-12 region of Nurr1 into
      NGFI-B results in a modest increase of activity. These observations reveal a high
      sensitivity of LBD activity to changes that influence helix 12 positioning.
      Furthermore, mutation of hydrophobic surface residues in the helix 11-12 region
      (outside the canonical co-activator surface constituted by helices 3, 4, and 12)
      severely affects Nurr1 transactivation. Together, our data suggest that a novel
      co-regulator surface that includes helix 11 and a specifically positioned helix
      12 determine the cell type-dependent activities of the NGFI-B and the Nurr1 LBD.

PMID- 15716273
TI  - Phosphorylated retinoblastoma protein complexes with pp32 and inhibits pp32
      mediated apoptosis.
AB  - The retinoblastoma gene product (Rb) is a tumor suppressor that affects apoptosis
      paradoxically. Most sporadic cancers inactivate Rb by preferentially targeting
      the pathway that regulates Rb phosphorylation, resulting in resistance to
      apoptosis; this contrasts with Rb inactivation by mutation, which is associated
      with high rates of apoptosis. How phosphorylated Rb protects cells from apoptosis
      is not well understood, but there is evidence that Rb may sequester a pro
      apoptotic nuclear factor. pp32 (ANP32A) is a pro-apoptotic nuclear
      phosphoprotein, the expression of which is commonly increased in cancer. We
      report that hyperphosphorylated Rb interacts with pp32 but not with the closely
      related proteins pp32r1 and pp32r2. We further demonstrate that pp32-Rb
      interaction inhibits the apoptotic activity of pp32 and stimulates proliferation.
      These results suggest a mechanism whereby cancer cells gain both a proliferative
      and survival advantage when Rb is inactivated by hyperphosphorylation.

PMID- 15716274
TI  - Tetrameric architecture of the circadian clock protein KaiB. A novel interface
      for intermolecular interactions and its impact on the circadian rhythm.
AB  - Cyanobacteria are among the simplest organisms that show daily rhythmicity. Their
      circadian rhythms consist of the localization, interaction, and accumulation of
      various proteins, including KaiA, KaiB, KaiC, and SasA. We have determined the
      1.9-angstroms resolution crystallographic structure of the cyanobacterial KaiB
      clock protein from Synechocystis sp. PCC6803. This homotetrameric structure
      reveals a novel KaiB interface for protein-protein interaction; the protruding
      hydrophobic helix-turn-helix motif of one subunit fits into a groove between two
      beta-strands of the adjacent subunit. A cyanobacterial mutant, in which the Asp
      Lys salt bridge mediating this tetramer-forming interaction is disrupted by
      mutation of Asp to Gly, exhibits severely impaired rhythmicity (a short free
      running period; approximately 19 h). The KaiB tetramer forms an open square, with
      positively charged residues around the perimeter. KaiB is localized on the
      phospholipid-rich membrane and translocates to the cytosol to interact with the
      other Kai components, KaiA and KaiC. KaiB antagonizes the action of KaiA on KaiC,
      and shares a sequence-homologous domain with the SasA kinase. Based on our
      structure, we discuss functional roles for KaiB in the circadian clock.

PMID- 15716275
TI  - Failure to assemble the alpha 3 beta 3 subcomplex of the ATP synthase leads to
      accumulation of the alpha and beta subunits within inclusion bodies and the loss
      of mitochondrial cristae in Saccharomyces cerevisiae.
AB  - The F(1) component of mitochondrial ATP synthase is an oligomeric assembly of
      five different subunits, alpha, beta, gamma, delta, and epsilon. In terms of
      mass, the bulk of the structure ( approximately 90%) is provided by the alpha and
      beta subunits, which form an (alphabeta)(3) hexamer with adenine nucleotide
      binding sites at the alpha/beta interfaces. We report here ultrastructural and
      immunocytochemical analyses of yeast mutants that are unable to form the
      alpha(3)beta(3) oligomer, either because the alpha or the beta subunit is missing
      or because the cells are deficient for proteins that mediate F assembly (e.g.
      Atp11p, Atp12p, or Fmc1p). The F(1) alpha(1) and beta subunits of such mutant
      strains are detected within large electron-dense particles in the mitochondrial
      matrix. The composition of the aggregated species is principally full-length F(1)
      alpha and/or beta subunit protein that has been processed to remove the amino
      terminal targeting peptide. To our knowledge this is the first demonstration of
      mitochondrial inclusion bodies that are formed largely of one particular protein
      species. We also show that yeast mutants lacking the alpha(3)beta(3) oligomer are
      devoid of mitochondrial cristae and are severely deficient for respiratory
      complexes III and IV. These observations are in accord with other studies in the
      literature that have pointed to a central role for the ATP synthase in biogenesis
      of the mitochondrial inner membrane.

PMID- 15716276
TI  - The regulation of hepatic protein synthesis during fasting in the rat.
AB  - We have studied translational control in the model of 48 h of fasting in the rat.
      Our initial observations showed a paradoxical increase in ribosomal protein S6
      (rpS6) phosphorylation and a decrease in eukaryotic initiation factor 2alpha
      (eIF2alpha) phosphorylation. These effects, which would favor an increase in
      protein synthesis, could be attributed to increased circulating concentrations of
      branched-chain amino acids in fasting. To determine what mechanisms might account
      for decreased hepatic translation in fasting, we examined the cap binding
      complex. eIF4E-bound 4E-BP1 did not increase. However, eIF4E-bound eIF4G and
      total cellular eIF4G were profoundly decreased in fasted liver. eIF4G mRNA levels
      were not lower after fasting. Based on the hypothesis that decreased eIF4G
      translation might account for the reduced eIF4G content, we fractionated
      ribosomes by sucrose density centrifugation. Immunoblotting for rpS6 showed
      modest polysomal disaggregation upon fasting. PCR analysis of polysome profiles
      revealed that a spectrum of mRNAs undergo different translational regulation in
      the fasted state. In particular, eIF4G was minimally affected by fasting. This
      indicated that reduced eIF4G abundance in fasting may be a function of its
      stability, whereas its recovery upon refeeding is necessarily independent of its
      own involvement in the cap binding complex. Western immunoblotting of polysome
      fractions showed that phosphorylated rpS6 was disproportionately present in
      translating polysomes in fed and fasted animals, consistent with a role in
      translational control. However, the translation of rpS8, an mRNA with a 5'
      oligopyrimidine tract, did not coincide with rpS6 phosphorylation, thus
      dissociating rpS6 phosphorylation from the translational control of this subset
      of mRNAs.

PMID- 15716277
TI  - Parathymosin affects the binding of linker histone H1 to nucleosomes and remodels
      chromatin structure.
AB  - Linker histone H1 is the major factor that stabilizes higher order chromatin
      structure and modulates the action of chromatin-remodeling enzymes. We have
      previously shown that parathymosin, an acidic, nuclear protein binds to histone
      H1 in vitro and in vivo. Confocal laser scanning microscopy reveals a nuclear
      punctuate staining of the endogenous protein in interphase cells, which is
      excluded from dense heterochromatic regions. Using an in vitro chromatin
      reconstitution system under physiological conditions, we show here that
      parathymosin (ParaT) inhibits the binding of H1 to chromatin in a dose-dependent
      manner. Consistent with these findings, H1-containing chromatin assembled in the
      presence of ParaT has reduced nucleosome spacing. These observations suggest that
      interaction of the two proteins might result in a conformational change of H1.
      Fluorescence spectroscopy and circular dichroism-based measurements on mixtures
      of H1 and ParaT confirm this hypothesis. Human sperm nuclei challenged with ParaT
      become highly decondensed, whereas overexpression of green fluorescent protein-
      or FLAG-tagged protein in HeLa cells induces global chromatin decondensation and
      increases the accessibility of chromatin to micrococcal nuclease digestion. Our
      data suggest a role of parathymosin in the remodeling of higher order chromatin
      structure through modulation of H1 interaction with nucleosomes and point to its
      involvement in chromatin-dependent functions.

PMID- 15716278
TI  - Smad6s regulates plasminogen activator inhibitor-1 through a protein kinase C
      beta-dependent up-regulation of transforming growth factor-beta.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a serpin class protease inhibitor
      that plays a central role in the regulation of vascular function and tissue
      remodeling by modulating thrombosis, inflammation, and the extracellular matrix.
      A central mediator controlling PAI-1 is transforming growth factor-beta (TGF
      beta), which induces its expression and promotes fibrosis. We have found that a
      unique member of the Smad family of signal transduction molecules, Smad6s,
      modulates the expression of PAI-1. Overexpression of Smad6s in endothelial cells
      increases promoter activity and PAI-1 secretion, and an antisense to Smad6s
      suppresses the induction of PAI-1 by TGF-beta. The effect of Smad6s on the PAI-1
      promoter appeared to be the result of increase binding of the forkhead winged
      helix factor FoxD1 to a TGF-beta-responsive element. Furthermore, the effect of
      Smad6s on PAI-1 up-regulation and on FoxD1 binding was found to result from up
      regulation of TGF-beta and could be inhibited by the blocking TGF-beta signaling
      with Smad7. The ability of Smad6s to regulate the TGF-beta promoter and
      subsequent PAI-1 induction was suppressed by a selective protein kinase C-beta
      (PKC-beta) inhibitor. Consistent with the in vitro data, we found that increased
      Smad6s in diseased vessels correlated with increased TGF-beta and PAI-1 levels.
      Overall, our results demonstrate that the level of Smad6s can alter the level of
      TGF-beta and the subsequent induction of PAI-1 via a FoxD1 transcription site.
      Furthermore, our data suggest that this process, which is up-regulated in
      diseased vessels, can be modulated by the inhibition of PKC-beta.

PMID- 15716279
TI  - Membrane topology mapping of vitamin K epoxide reductase by in vitro
      translation/cotranslocation.
AB  - Vitamin K epoxide reductase (VKOR) catalyzes the conversion of vitamin K 2,3
      epoxide into vitamin K in the vitamin K redox cycle. Recently, the gene encoding
      the catalytic subunit of VKOR was identified as a 163-amino acid integral
      membrane protein. In this study we report the experimentally derived membrane
      topology of VKOR. Our results show that four hydrophobic regions predicted as the
      potential transmembrane domains in VKOR can individually insert across the
      endoplasmic reticulum membrane in vitro. However, in the intact enzyme there are
      only three transmembrane domains, residues 10-29, 101-123, and 127-149, and
      membrane-integration of residues 75-97 appears to be suppressed by the
      surrounding sequence. Results of N-linked glycosylation-tagged full-length VKOR
      shows that the N terminus of VKOR is located in the endoplasmic reticulum lumen,
      and the C terminus is located in the cytoplasm. Further evidence for this
      topological model of VKOR was obtained with freshly prepared intact microsomes
      from insect cells expressing HPC4-tagged full-length VKOR. In these experiments
      an HPC4 tag at the N terminus was protected from proteinase K digestion, whereas
      an HPC4 tag at the C terminus was susceptible. Altogether, our results suggest
      that VKOR is a type III membrane protein with three transmembrane domains, which
      agrees well with the prediction by the topology prediction program TMHMM.

PMID- 15716280
TI  - Regulation of monocyte apoptosis by the protein kinase Cdelta-dependent
      phosphorylation of caspase-3.
AB  - Monocytes are central components of the innate immune response and normally
      circulate for a short period of time before undergoing spontaneous apoptosis.
      During inflammation, differentiation, or oncogenic transformation, the life span
      of monocytes is prolonged by preventing the activation of the apoptotic program.
      Here we showed that caspase-3, a cysteine protease required for monocyte
      apoptosis, is a phosphoprotein. We identified protein kinase Cdelta (PKCdelta) as
      a member of the protein kinase C family that associates with and phosphorylates
      caspase-3. The PKCdelta-dependent phosphorylation of caspase-3 resulted in an
      increase in the activity of caspase-3. This effect of PKCdelta is specific to
      caspase-3, as evidenced by the absence of similar effects on caspase-9. The
      activity of PKCdelta precedes the activation of caspase-3 during spontaneous
      monocyte apoptosis and in monocyte-induced apoptosis. We found that the
      overexpression of PKCdelta resulted in an increase of apoptosis, whereas its
      inhibition blocked caspase-3 activity and decreased apoptosis. Our results
      provided evidence that the PKCdelta-dependent phosphorylation of caspase-3
      provided a novel pro-apoptotic mechanism involved in the regulation of monocyte
      life span.

PMID- 15716281
TI  - Impact of combined pharmacologic treatment with clopidogrel and a statin on
      outcomes of patients with non-ST-segment elevation acute coronary syndromes:
      perspectives from a large multinational registry.
AB  - AIMS: To evaluate clinical outcomes associated with the combined use of
      clopidogrel and statins vs. clopidogrel alone on a background of aspirin therapy
      in patients with the spectrum of acute coronary syndromes (ACS). METHODS AND
      RESULTS: Utilizing data from the Global Registry of Acute Coronary Events, we
      studied 15 693 patients admitted with non-ST-segment elevation myocardial
      infarction (MI) or unstable angina, dividing them according to discharge
      medications: aspirin alone (group I); aspirin + clopidogrel (group II); aspirin +
      statin (group III); aspirin + clopidogrel + statin (group IV). Among the groups
      of patients in whom clopidogrel was used (groups II and IV), group II patients
      were older, more likely to have prior MI, but less likely to have a history of
      prior revascularization. In-hospital cardiac catheterization and
      revascularization rates were similar between groups II and IV. Importantly,
      Kaplan-Meier analysis showed that the 6 month mortality rate was lower in group
      IV (log-rank test 22.8, P<0.0001). The hazard ratio for the 6 month mortality
      rate was adjusted using the Cox proportional hazard model for confounding
      variables and for propensity score, and the 6 month mortality rate for patients
      in group IV remained lower compared with those in group II [0.59 (0.41-0.86),
      P<0.0001]. CONCLUSION: Our data suggest that the combination of clopidogrel with
      a statin has synergistic effects on the clinical outcomes of patients with non-ST
      segment elevation ACS.

PMID- 15716282
TI  - The effect of intra-aortic balloon counterpulsation on left ventricular
      functional recovery early after acute myocardial infarction: a randomized
      experimental magnetic resonance imaging study.
AB  - AIMS: We sought to determine whether intra-aortic balloon pump (IABP)
      counterpulsation improves the recovery of left ventricular (LV) systolic function
      after reperfused acute myocardial infarction (AMI). METHODS AND RESULTS: Fourteen
      dogs underwent 90-min coronary artery occlusion followed by reperfusion. Seven
      animals were randomized to IABP counterpulsation immediately after reperfusion.
      Tagged, cine, and contrast-enhanced magnetic resonance imaging were used for
      regional and global LV functional assessment and MI characterization,
      respectively. Image acquisition was performed at 1 h, 6 h, and 24 h after
      reperfusion, during which the IABP device was paused. Animals randomized to IABP
      demonstrated an earlier improvement of LV ejection fraction when compared with
      controls (25+/-3 vs. 25+/-2% at 1 h, P=0.91; 36+/-3 vs. 26+/-2% at 6 h, P=0.015;
      and 38+/-3 vs. 35+/-1% at 24 h, P=0.34). Regional functional analyses revealed
      the same behaviour among non-infarcted risk regions, i.e., earlier
      circumferential systolic strain improvement in the IABP group than in controls (
      5.4+/-0.4 vs. -5.3+/-0.5% at 1 h, P=0.86; -12.1+/-1.0 vs. -6.0+/-0.4% at 6 h,
      P<0.001; and -13.9+/-1.1% vs. -12.8+/-0.6% at 24 h, P=0.40). Importantly,
      however, the degree of LV functional recovery 24 h after reperfusion was similar
      whether IABP counterpulsation was used or not. CONCLUSION: IABP counterpulsation
      accelerates but does not significantly improve the recovery of LV systolic
      function after reperfused AMI.

PMID- 15716283
TI  - Recovery of left ventricular function after primary angioplasty for acute
      myocardial infarction.
AB  - AIMS: To study recovery of segmental wall thickening (SWT), ejection fraction
      (EF), and end-systolic volume (ESV) after acute myocardial infarction (AMI) in
      patients who underwent primary stenting with drug-eluting stents. Additionally,
      to evaluate the predictive value of magnetic resonance imaging (MRI)-based
      myocardial perfusion and delayed enhancement (DE) imaging. METHODS AND RESULTS:
      Twenty-two patients underwent cine-MRI, first-pass perfusion, and DE imaging 5
      days after successful placement of a drug-eluting stent in the infarct-related
      coronary artery. Regional myocardial perfusion and the transmural extent of DE
      were evaluated. A per patient perfusion score was calculated and consisted of a
      summation of all segmental scores. Myocardial infarct size was quantified by
      measuring the volume of DE. At 5 months after AMI, cine-MRI was performed and
      SWT, EF, and ESV were quantified. EF increased from 48+/-11 to 55+/-9% (P<0.01).
      SWT at 5 months was inversely related to baseline segmental DE scores (P<0.001)
      and segmental perfusion scores (P<0.001). EF and ESV at 5 months were related to
      acute infarct size (R(2)=0.65; P<0.001 and R(2)=0.78; P<0.001, respectively) and
      the calculated perfusion score (R(2)=0.23; P=0.02 and R(2)=0.14; P=0.09,
      respectively) at baseline. CONCLUSION: Marked recovery of left ventricular
      function was observed in patients receiving a drug-eluting stent for AMI. DE
      imaging appears to be a better prognosticator than perfusion imaging.

PMID- 15716284
TI  - The initial management of stable angina in Europe, from the Euro Heart Survey: a
      description of pharmacological management and revascularization strategies
      initiated within the first month of presentation to a cardiologist in the Euro
      Heart Survey of Stable Angina.
AB  - AIMS: In order to assess adherence to guidelines and international variability in
      management, the Euro Heart Survey of Newly Presenting Angina prospectively
      studied medical therapy, percutaneous coronary intervention (PCI), and surgery in
      patients with new-onset stable angina in Europe. METHODS AND RESULTS: Consecutive
      patients, 3779 in total, with a clinical diagnosis of stable angina by a
      cardiologist were enrolled. After initial assessment by a cardiologist, 78% were
      treated with aspirin, 48% with a statin, and 67% with a beta-blocker. ACE
      inhibitors were prescribed by the cardiologist in 37% overall. Revascularization
      rates were low, with only 501 (13%) patients having PCI or coronary bypass
      surgery performed or planned. However, when restricted to patients with coronary
      disease documented within 4 weeks of assessment, over 50% had revascularization
      performed or planned. Among other factors, the national rate of angiography and
      availability of invasive facilities significantly predicted the likelihood of
      revascularization, OR 2.4 and 2.0, respectively. CONCLUSION: This survey shows a
      shortfall between guidelines and practice with regard to the use of evidence
      based drug therapy and evidence that revascularization rates are strongly
      influenced by non-clinical, in addition to clinical, factors.

PMID- 15716285
TI  - Soluble CD40 ligand in acute and chronic heart failure.
AB  - AIMS: Inflammatory cytokines may play a pathogenic role in heart failure (HF).
      CD40-CD40 ligand (CD40L) interactions are important in atherogenesis and based on
      its role in inflammation we sought to evaluate the role of CD40L in human HF.
      METHODS AND RESULTS: Serum levels of soluble (s) CD40L were measured in 236
      patients with acute HF following myocardial infarction, treated with either
      angiotensin-converting enzyme (ACE)-inhibition or angiotensin II blockade and
      followed for 2 years, and in 116 patients with chronic HF. Our main findings
      were: (i) patients with acute HF had increased sCD40L levels, particularly those
      with severe HF, diabetes, or hypertension; (ii) when these patients were followed
      longitudinally, persistently raised sCD40L levels were found throughout the
      observation period with no effect of captopril or losartan; (iii) the increase in
      sCD40L during follow-up was not seen in patients receiving warfarin therapy; (iv)
      patients with chronic HF also had raised sCD40L, significantly correlated with
      clinical severity, neurohormonal dysregulation, and left ventricular dysfunction;
      (v) studies from different blood compartments suggest that the vasculature of
      lower extremities and the failing myocardium itself may produce and secrete
      sCD40L in chronic HF. CONCLUSION: Our findings may suggest a pathogenic role for
      enhanced CD40-CD40L interactions in human HF.

PMID- 15716286
TI  - Raising the loading dose of clopidogrel: aiming at the proper target?

PMID- 15716287
TI  - Cerebral emboli during left heart catheterization may cause acute brain injury.
AB  - AIMS: Left heart catheterization carries a risk for cerebral complications. The
      aims of this prospective study were to determine the frequency and composition of
      catheterization-related cerebral microemboli and to detect cerebral morphological
      changes and acute cognitive impairment due to catheterization. METHODS AND
      RESULTS: Forty-seven unselected patients undergoing elective left heart
      catheterization, either by transradial or by transfemoral access, were monitored
      for cerebral microemboli using multifrequency transcranial Doppler. Cerebral
      magnetic resonance imaging (MRI) with diffusion-weighted imaging sequences and
      neuropsychological assessments were carried out on the day before and the day
      after catheterization. A median number of 754 cerebral microemboli were detected:
      92.1% were gaseous and 7.9% were solid. New cerebral lesions were observed in
      15.2% of the transradial, but none of the transfemoral, catheterization patients
      (P=0.567). These lesions were significantly associated with a higher number of
      solid microemboli (P=0.016) and a longer fluoroscopy time (P=0.039). There was
      also a significantly higher number of solid microemboli during transradial than
      during transfemoral catheterization (P=0.012). Cognitive impairment following the
      investigations was associated with the degree of pre-catheterization cerebral MRI
      injury (P=0.03). CONCLUSION: During left heart catheterization, cerebral
      microemboli, especially those which are solid, may damage the brain. Cardiac
      catheterization may therefore pose a greater risk for the brain than previously
      acknowledged.

PMID- 15716288
TI  - Reduction of QRS duration after pulmonary valve replacement in adult Fallot
      patients is related to reduction of right ventricular volume.
AB  - AIMS: Late after total correction, Fallot patients with a long QRS duration are
      prone to serious arrhythmias and sudden cardiac death. Pulmonary regurgitation is
      a common cause of right ventricular (RV) failure and QRS lengthening. We studied
      the effects of pulmonary valve replacement (PVR) on QRS duration and RV volume.
      METHODS AND RESULTS: Twenty-six consecutive Fallot patients were evaluated both
      pre-operatively and 6-12 months post-operatively by cardiac magnetic resonance
      (CMR). In this study, we present the computer-assisted analysis of the standard
      12-lead electrocardiograms closest in time to the CMR studies. For the whole
      group, QRS duration shortened by 6+/-8 ms, from 151+/-30 to 144+/-29 ms
      (P=0.002). QRS duration decreased in 18 of 26 patients by 10+/-6 ms, from 152+/
      32 to 142+/-31 ms. QRS duration remained constant or increased slightly in eight
      of 26 patients by 3+/-3 ms, from 148+/-27 to 151+/-25 ms. CMR showed a decrease
      in RV end-diastolic volume from 305+/-87 to 210+/-62 mL (P=0.000004). QRS
      duration changes correlated with RV end-diastolic volume changes (r=0.54,
      P=0.01). CONCLUSION: Our study shows that PVR reduces QRS duration. The amount of
      QRS reduction is related to the success of the operation, as expressed by the
      reduction in RV end-diastolic volume.

PMID- 15716289
TI  - Cost effectiveness of nurse led secondary prevention clinics for coronary heart
      disease in primary care: follow up of a randomised controlled trial.
AB  - OBJECTIVE: To establish the cost effectiveness of nurse led secondary prevention
      clinics for coronary heart disease based on four years' follow up of a randomised
      controlled trial. DESIGN: Cost effectiveness analysis. SETTING: 19 general
      practices in north east Scotland. PARTICIPANTS: 1343 patients (673 in
      intervention group and 670 in control group, as originally randomised) aged under
      80 years with a diagnosis of coronary heart disease but without terminal illness
      or dementia and not housebound. INTERVENTION: Nurse led clinics to promote
      medical and lifestyle components of secondary prevention. MAIN OUTCOME MEASURES:
      Costs of clinics; overall costs to health service; and cost per life year and per
      quality adjusted life year (QALY) gained, expressed as incremental gain in
      intervention group compared with control group. RESULTS: The cost of the
      intervention (clinics and drugs) was 136 pounds sterling (254 dollars; 195 euros)
      per patient higher (1998-9 prices) in the intervention group, but the difference
      in other NHS costs, although lower for the intervention group, was not
      statistically significant. Overall, 28 fewer deaths occurred in the intervention
      group leading to a gain in mean life years per patient of 0.110 and of 0.124
      QALYs. The incremental cost per life year saved was 1236 pounds sterling and that
      per QALY was 1097 pounds sterling. CONCLUSION: Nurse led clinics for the
      secondary prevention of coronary heart disease in primary care seem to be cost
      effective compared with most interventions in health care, with the main gains in
      life years saved.

PMID- 15716290
TI  - Reply to the article "Metronomic therapy with cyclophosphamide induces rat
      lymphoma and sarcoma regression, and is devoid of toxicity" by V. R. Rozados et
      al. (Ann Oncol 2004; 15: 1543-1550): ... and in humans?

PMID- 15716291
TI  - Rhabdomyolysis due to hypothyroidism.

PMID- 15716292
TI  - A male nephrotic patient with rapid decline of renal function.

PMID- 15716293
TI  - Persistent cytomegalovirus infection is associated with increased expression of
      TGF-beta1, PDGF-AA and ICAM-1 and arterial intimal thickening in kidney
      allografts.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a suggested risk factor for the development
      of chronic allograft nephropathy. Transforming growth factor-beta (TGF-beta) and
      platelet-derived growth factor (PDGF) are important molecules in this process. We
      analysed the impact of persistent CMV infection in kidney allografts on the
      expression of growth factors, adhesion molecules and inflammation markers.
      METHODS: In a population of 172 renal transplant recipients, CMV was diagnosed in
      82 patients by pp65 antigenaemia test and viral cultures. Biopsies taken after
      CMV infection were available from 48 of the 82 patients for the demonstration of
      CMV antigens by immunohistochemistry and in situ DNA hybridization. Biopsy
      material for further analyses was available from 16 CMV patients. Five patients
      with no previous CMV infection were used as controls. Biopsy histology was scored
      according to Banff 97 classification. RESULTS: In 11 out of 16 patients,
      persistent CMV antigens and/or DNA were demonstrated in the biopsy >2 months
      after the last positive finding in blood or urine. Increased expression of TGF
      beta1 was recorded in tubuli and in arterial endothelium in biopsies with a
      positive CMV finding compared with controls. Also, the expression of PDGF-AA was
      increased in tubuli and somewhat in arterial endothelium in CMV-positive
      biopsies. The expression of intercellular adhesion molecule-1 (ICAM-1) was
      increased significantly in peritubular capillary endothelium. Vascular intimal
      thickening was increased in the biopsies with persistent CMV infection.
      CONCLUSIONS: Persistent CMV infection in kidney allografts was associated with
      increased vascular changes and increased expression of TGF-beta1, PDGF-AA and
      ICAM-1.

PMID- 15716294
TI  - Macrophage-derived interleukin-18 in experimental renal allograft rejection.
AB  - BACKGROUND: Interleukin 18 (IL-18) is primarily a macrophage-derived, pro
      inflammatory cytokine. As macrophages can act as effector cells in acute
      rejection, we examined the role of IL-18 in a rat model of acute renal allograft
      rejection. METHODS: Life-sustaining orthotopic DA to Lewis allograft and Lewis
      Lewis isograft kidney transplants were performed. In the same model, macrophage
      depleted animals, achieved with liposomal-clodronate therapy, were also studied.
      Macrophage (ED1+) accumulation and IL-18 expression was assessed by
      immunohistochemistry. CD11b+ cells (macrophages) were isolated from kidney and
      spleen by micro beads. Real-time PCR was used to assess IL-18 and INF-gamma mRNA
      expression in tissue and cell isolates. RESULTS: Allografts, but not isografts,
      developed severe tubulo-interstitial damage and increased serum creatinine by day
      5 (P<0.001). Immunohistochemistry revealed a greater ED1+ cell accumulation in
      day 5 allografts compared with isografts (P<0.001). IL-18 mRNA expression was
      increased 3-fold in allografts compared to isografts (P<0.001). Accordingly, IL
      18 protein was increased in allografts (P<0.001), and was predominantly expressed
      by ED1+ macrophages. CD11b+ macrophages isolated from allografts had a 6-fold
      upregulation of IL-18 mRNA expression compared to isograft macrophages (P<0.001).
      Macrophage depletion resulted in a marked attenuation of allograft rejection,
      ED1+ and IL-18+ cells were significantly reduced (P<0.05) as was IL-18 mRNA
      expression (29.28+/-2.85 vs 62.48+/-3.05, P<0.001). INF-gamma mRNA expression
      (P<0.01) and iNOS (P<0.001) production were also significantly reduced in the
      macrophage-depleted animals. CONCLUSION: This study demonstrates that IL-18 is
      significantly increased during acute rejection and is principally produced by
      intra-graft macrophages. We hypothesize that IL-18 upregulation may be an
      important macrophage effector mechanism during the acute rejection process.

PMID- 15716295
TI  - Recurrent rhabdomyolysis and mild acute renal failure associated with acute
      Brucella infection.

PMID- 15716296
TI  - Atherosclerosis and vascular calcification are independent predictors of left
      ventricular hypertrophy in chronic haemodialysis patients.
AB  - BACKGROUND: Accelerated atherosclerosis and vascular calcification are common in
      chronic haemodialysis (HD) patients. In this study, we aimed to investigate the
      relationship between left ventricular hypertrophy (LVH) in HD patients and
      atherosclerosis and vascular calcification measured by electron beam computed
      tomography (EBCT). METHODS: In a cohort of 118 HD patients (52 male, 66 female,
      mean age: 46+/-13 years), we measured biochemical parameters, including BUN,
      creatinine, albumin, haemoglobin, C-reactive protein and fibrinogen levels, and
      performed echocardiography, high-resolution B-mode carotid ultrasonography and
      EBCT in 85 of them. The degree of stenosis was measured at four different sites
      (communis, bulbus, interna and externa) in both carotid arteries. Carotid plaque
      scores were calculated by summing the degrees of stenosis measured at all
      locations. RESULTS: LVH was detected in 89 of the patients (75%). Plaque-positive
      patients had higher left ventricular mass index (LVMI) than plaque-negative
      patients (175+/-59 vs 143+/-46 g/m2, P = 0.003). LVMI was correlated with
      systolic blood pressure (r = 0.62, P<0.001), pulse pressure (r = 0.58, P<0.001),
      haemoglobin levels (r = - 0.25, P = 0.008), carotid plaque score (r = 0.32, P =
      0.001) and coronary (CACS) and aortic wall calcification score (AWCS) (r = 0.34,
      P = 0.002 and r = 0.43, P<0.001, respectively). Multiple linear regression
      analysis (model r = 0.76) showed the independent factors related to LVMI to be
      systolic blood pressure, pulse pressure, CACS and presence of carotid plaques.
      CONCLUSION: Extra-coronary atherosclerosis and vascular calcification are
      associated with LVH in HD patients. Whether the treatment of atherosclerosis or
      vascular calcification may cause regression of or even prevent LVH in HD patients
      remains to be seen.

PMID- 15716297
TI  - Optimality principle and determination of kinetic constants for biochemical
      reactions.
AB  - An optimality principle is applied to determine kinetic constants for biochemical
      (enzymatic and second-order) reactions involved in a physiological system, a
      minimum protein consumption criterion being adopted. A direct optimization
      problem is to determine optimal zymogen concentrations. An 'inverse' optimization
      problem is also considered; this problem is to determine the kinetic constants
      for the biochemical reactions involved in a physiological system such that the
      optimal and observed zymogen and procofactor concentrations coincide. In solving
      an 'inverse' optimization problem we assume that the scheme of biochemical
      reactions and zymogen and procofactor concentrations are known. Good agreement is
      observed between the model results for the extrinsic blood coagulation pathway
      and relevant biochemical data. The proposed method is also applicable to
      determining kinetic constants for other physiological biochemical-reaction
      systems.

PMID- 15716298
TI  - A delay-differential equation model of the feedback-controlled hypothalamus
      pituitary-adrenal axis in humans.
AB  - The present work develops and analyses a model system of delay-differential
      equations which describes the core dynamics of the stress-responsive hypothalamus
      pituitary-adrenal axis. This neuroendocrine ensemble exhibits prominent pulsatile
      secretory patterns governed by nonlinear and time-delayed feedforward and
      feedback signal interchanges. Formulation and subsequent bifurcation analysis of
      the model provide a qualitative and mathematical frame work for a better
      understanding of the delayed responsive mechanisms as well as the dynamic
      variations in different pathological situations.

PMID- 15716299
TI  - Resting shape and spontaneous membrane curvature of red blood cells.
AB  - A boundary-value problem is formulated describing the biconcave resting shape of
      normal red blood cells, based on local constitutive equations for the membrane
      tensions and bending moments. The fundamental physical assumption is that
      curvature-dependent anisotropic membrane stress resultants accompanied by
      isotropic bending moments arise from isotropic tensions developing in each
      leaflet of the lipid bilayer, while the cytoskeleton is unstressed in the resting
      configuration. Families of equilibrium resting shapes parametrized by the
      spontaneous bilayer curvature and cell sphericity compare favourably with the
      average shape of normal red blood cells. The successful comparison supports
      Helfrich's notion of a non-zero spontaneous curvature whose magnitude is nearly
      equal to the negative of the equivalent cell radius defined with respect to the
      membrane surface area. The structure of the solution space suggests a minimum
      spontaneous curvature below which the cell sphericity is lower than that of the
      red blood cell, independent of the transmural pressure. The computed cell shapes
      also compare favourably with the shapes of swollen red blood cells, though for a
      different value of the spontaneous curvature. The dependence of the spontaneous
      curvature on the cell volume is attributed to in-plane elastic tensions
      developing due to the deformation of the cytoskeleton. An alternative formulation
      based on a non-local model for the monolayer tensions is found to be incapable of
      predicting non-spherical shapes.

PMID- 15716300
TI  - Thin-film theories for two-phase reactive flow models of active cell motion.
AB  - The aim of this paper is to develop a broadly-applicable and self-consistent thin
      film biphasic modelling framework for the full crawling cycle of a single animal
      cell. A hierarchy of thin-film two-phase 'reactive flow' models is derived;
      between them these cover a wide range of biologically relevant parameter regimes.
      The mathematical properties and biological implications of the resulting systems
      of high-order nonlinear degenerate parabolic-elliptic evolution equations are
      investigated. Linear-stability arguments suggest the formation of highly
      localized regions of high or low network density associated with small irregular
      oscillations or 'ruffling' of the plasma membrane. Local analyses at the contact
      line identify the classes of admissible contact-line conditions, through which we
      study for the first time the effect on the cell-scale motion of the 'mesoscopic'
      contact-line physics, which consists of the chemical and mechanical mechanisms
      for protrusive and retractive force generation near the outer cell periphery. One
      of the formulations is used to develop a minimal model for cell body
      translocation over a thin pseudopod, which predicts that myosin-driven
      contraction is not essential for rapid translocation. An analytic prediction for
      the translocation speed is given in terms of the network viscosity and slip
      coefficient (a parameter measuring the adhesion strength), of the membrane
      tension and of the thicknesses of the pseudopod and actin cortex; this is in good
      agreement with the translocation speed of osteoblasts on biomaterial substrates
      commonly used for orthopaedic implants. Limitations of the modelling approach and
      directions for future work are outlined.

PMID- 15716301
TI  - Mathematical models for pressure controlled ventilation of oleic acid-injured
      pigs.
AB  - One-compartment, mathematical models for pressure controlled ventilation,
      incorporating volume dependent compliances, linear and nonlinear resistances, are
      constructed and compared with data obtained from healthy and (oleic acid) lung
      injured pigs. Experimental data are used to find parameters in the mathematical
      models and were collected in two forms. Firstly, the P(e)-V curves for healthy
      and lung injured pigs were constructed; these data are used to compute compliance
      functions for each animal. Secondly, dynamic data from pressure controlled
      ventilation for a variety of applied pressures are used to estimate resistance
      parameters in the models. The models were then compared against the collected
      dynamic data. The best mathematical models are ones with compliance functions of
      the form C(V) = a + bV where a and b are constants obtained from the P(e)-V
      curves and the resistive pressures during inspiration change from a linear
      relation P(r) = RQ to a nonlinear relation P(r) = RQ(epsilon) where Q is the flow
      into the one-compartment lung and epsilon is a positive number. The form of the
      resistance terms in the mathematical models indicate the possible presence of gas
      liquid foams in the experimental data.

PMID- 15716302
TI  - Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation
      in the limbic system.
AB  - The reason for the high frequency of depression and anxiety in Parkinson's
      disease is poorly understood. Degeneration of neurotransmitter systems other than
      dopamine might play a specific role in the occurrence of these affective
      disorders. We used [11C]RTI-32 PET, an in vivo marker of both dopamine and
      noradrenaline transporter binding, to localize differences between depressed and
      non-depressed patients. We studied eight and 12 Parkinson's disease patients with
      and without a history of depression matched for age, disease duration and doses
      of antiparkinsonian medication. The depressed Parkinson's disease cohort had
      lower [11C]RTI-32 binding than non-depressed Parkinson's disease cases in the
      locus coeruleus and in several regions of the limbic system including the
      anterior cingulate cortex, the thalamus, the amygdala and the ventral striatum.
      Exploratory analyses revealed that the severity of anxiety in the Parkinson's
      disease patients was inversely correlated with the [11C]RTI-32 binding in most of
      these regions and apathy was inversely correlated with [11C]RTI-32 binding in the
      ventral striatum. These results suggest that depression and anxiety in
      Parkinson's disease might be associated with a specific loss of dopamine and
      noradrenaline innervation in the limbic system.

PMID- 15716303
TI  - Peripheral projections of sensory fascicles in the human superficial radial
      nerve.
AB  - The sensory territories of different cutaneous fascicles of the superficial
      radial nerve were delineated by microneurography at the level of the distal
      forearm in humans. Three fascicular patterns were found at this level: one
      supplying the dorsum of the radial aspect of the dorsum of the hand over the
      first dorsal interosseous space; another supplying the lateral aspect of the
      first metacarpal extending to the lateral aspect of the thumb; and a third
      innervating the second interosseous space and the proximal phalanx of the index
      and middle fingers. The compound fascicular territory is comparable to the
      classical territory described for the superficial radial nerve. Intraneural
      microstimulation of individual fascicles did not evoke paraesthesiae or pain
      beyond their fascicular territory, regardless of the stimulus intensity. We
      conclude that the superficial radial nerve at the forearm in man is composed of
      only three fascicles, as shown by the present study and from previous anatomical
      work. Referred pain seems related to nerve activity in afferent fibres from
      fascicles supplying deep tissues and muscles, not from cutaneous afferents.

PMID- 15716304
TI  - Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit
      enhanced brain expression of P-glycoprotein compared with rats with drug
      responsive seizures.
AB  - Medical intractability, i.e. the absence of any response to anti-epileptic drug
      (AED) therapy, is an unresolved problem in many patients with epilepsy.
      Mechanisms of intractability are not well understood, but may include alterations
      of pharmacological targets and poor penetration of AEDs into the brain because of
      increased expression of multiple drug-resistance proteins, such as P-glycoprotein
      (Pgp; ABCB1), capable of active brain extrusion of various drugs, including AEDs.
      Increased expression of Pgp has been reported in brain tissue of patients with
      refractory epilepsy, but there is a lack of adequate controls, i.e. brain tissue
      from patients with drug-responsive epilepsy. In the present study, we used a rat
      model of temporal lobe epilepsy to examine whether AED responders differ from non
      responders in their expression of Pgp in the brain. In this model, spontaneous
      recurrent seizures develop after status epilepticus induced by prolonged
      electrical stimulation of the basolateral amygdala. The frequency of these
      seizures was recorded by continuous video-EEG monitoring before, during and after
      daily treatment with phenobarbital, which was given at maximum tolerated doses
      for 2 weeks. Based on their individual response to phenobarbital, rats were
      grouped into responders (n = 7) and non-responders (n = 4). Pgp expression was
      studied by immunohistochemistry and showed striking overexpression in non
      responders compared with responders in limbic brain regions, including the
      hippocampus. The Pgp overexpression was confined to brain capillary endothelial
      cells which form the blood-brain barrier. The present data are the first to
      demonstrate that rats with drug-resistant spontaneous seizures differ from rats
      with drug-responsive seizures in their Pgp expression in the brain, thereby
      substantiating the multidrug transporter hypothesis of intractable epilepsy.

PMID- 15716305
TI  - NT-3 expression from engineered olfactory ensheathing glia promotes spinal
      sparing and regeneration.
AB  - Adenoviral (AdV) vectors encoding neurotrophin-3 (AdV-NT-3) or the bacterial
      marker enzyme beta-galactosidase (LacZ gene) were used to transduce olfactory
      ensheathing glia (OEG) cultures. AdV vector-transduced OEG expressed high levels
      of recombinant neurotrophin as shown by in situ hybridization and enzyme-linked
      immunosorbent assay techniques. The biological activity of vector-derived NT-3
      was determined in a dorsal root ganglia neurite outgrowth assay. Engineered cell
      suspensions were then injected into adult Fischer 344 rat spinal cord immediately
      after unilateral cervical (C4) corticospinal tract (CST) transection.
      Transplanted animals received a total of 200,000 cells; either non-transduced OEG
      or OEG transduced with AdV vectors encoding NT-3 or LacZ, respectively. At 3
      months after injury, lesion volumes were significantly smaller in all OEG
      transplanted rats when compared with control (medium-injected) rats. Anterograde
      tracing of the lesioned CST projection, originating from the contralateral
      sensorimotor cortex, showed a significantly greater number of distal CST axons
      only in OEG-NT-3-transplanted rats. Behavioural analysis was performed on all
      rats using open field locomotion scoring, and a forelimb reaching task with
      Eshkol-Wachman movement notation. Analysis of behavioural tests revealed no
      significant differences in recovery between experimental groups, although
      movement analysis indicated that possible compensatory mechanisms were occurring
      after OEG implantation. The results demonstrate that OEG transplantation per se
      can promote tissue sparing after injury, but, after appropriate genetic
      modification, these olfactory-derived cells become far more effective in
      promoting long-distance maintenance/regeneration of lesioned adult CST axons.

PMID- 15716306
TI  - Reading skills after left anterior temporal lobe resection: an fMRI study.
AB  - Maintaining language functions after left hemisphere lesions has been associated
      with compensatory right hemisphere activation. It remains unclear whether
      recruitment of right hemisphere regions necessarily provides an effective
      mechanism to compensate for language deficits. To investigate the compensatory
      mechanisms that mediate good reading skills in patients after left anterior
      temporal lobe resection for mesial temporal lobe epilepsy (mTLE), we tested for
      the effect of their reading ability on the regional fMRI (functional MRI) signal
      elicited by sentence reading. Sixteen control subjects and 16 patients
      participated in the study. In the activation condition, they silently read nine
      word sentences, and in the baseline condition they viewed nine-word sentences
      after all the letters were transformed into false fonts. Reading ability in
      controls and patients significantly (P < 0.05, corrected) predicted activations
      in a left hemisphere middle temporal region that was part of the normal sentence
      reading system. In addition, reading ability in patients, but not controls,
      significantly predicted activation in the right inferior frontal sulcus, right
      hippocampus and right inferior temporal sulcus. Right inferior frontal activation
      was only observed in the patients. In contrast, right hippocampal and inferior
      temporal activation was observed in all controls and in patients whose reading
      ability was within the normal range, indicating the importance of these regions
      for efficient encoding during normal sentence reading. We conclude that
      proficient reading skills following left anterior temporal lobe resection for
      mTLE rely on two mechanisms: (i) integrating regions from the normal system (i.e.
      the left middle temporal, right hippocampus and anterior superior temporal
      sulcus); and (ii) recruiting right hemisphere regions (i.e. the right inferior
      frontal sulcus) that are not activated in control subjects.

PMID- 15716307
TI  - Downregulation of eRF1 by RNA interference increases mis-acylated tRNA
      suppression efficiency in human cells.
AB  - The site-specific incorporation of non-natural amino acids into proteins by
      nonsense suppression has been widely used to investigate protein structure and
      function. Usually this technique exhibits low incorporation efficiencies of non
      natural amino acids into proteins. We describe for the first time an approach for
      achieving an increased level of nonsense codon suppression with synthetic
      suppressor tRNAs in cultured human cells. We find that the intracellular
      concentration of the eukaryotic release factor 1 (eRF1) is a critical parameter
      influencing the efficiency of amino acid incorporation by nonsense suppression.
      Using RNA interference we were able to lower eRF1 gene expression significantly.
      We achieved a five times higher level of amino acid incorporation as compared
      with non-treated control cells, as demonstrated by enhanced green fluorescent
      protein (EGFP) fluorescence recovery after importing a mutated reporter mRNA
      together with an artificial amber suppressor tRNA.

PMID- 15716308
TI  - Reproducibility, bioinformatic analysis and power of the SAGE method to evaluate
      changes in transcriptome.
AB  - The serial analysis of gene expression (SAGE) method is used to study global gene
      expression in cells or tissues in various experimental conditions. However, its
      reproducibility has not yet been definitively assessed. In this study, we have
      evaluated the reproducibility of the SAGE method and identified the factors that
      affect it. The determination coefficient (R2 ) for the reproducibility of SAGE is
      0.96. However, there are some factors that can affect the reproducibility of
      SAGE, such as the replication of concatemers and ditags, the number of sequenced
      tags and double PCR amplification of ditags. Thus, corrections for these factors
      must be made to ensure the reproducibility and accuracy of SAGE results. A
      bioinformatic analysis of SAGE data is also presented in order to eliminate these
      artifacts. Finally, the current study shows that increasing the number of
      sequenced tags improves the power of the method to detect transcripts and their
      regulation by experimental conditions.

PMID- 15716309
TI  - Use of mRNA- and protein-destabilizing elements to develop a highly responsive
      reporter system.
AB  - Reporter assays are widely used in applications that require measurement of
      changes in gene expression over time (e.g. drug screening). With standard
      reporter vectors, the measurable effect of a treatment or compound (altered
      reporter activity) is substantially diluted and delayed, compared with its true
      effect (altered transcriptional activity). This problem is caused by the
      relatively long half-lives of both the reporter protein and its mRNA. As a
      result, the activities of compounds, ligands or treatments that have a relatively
      minor effect, or a substantial but transient effect, often remain undetected. To
      circumvent this problem, we introduced modular protein- and mRNA-destabilizing
      elements into a range of commonly used reporters. Our data show that both
      elements are required for maximal responses to both increases and decreases in
      transcriptional activity. The double-destabilized reporter vectors showed
      markedly improved performance in drug screening, kinetic assays and dose-response
      titrations.

PMID- 15716310
TI  - A new computational method for the detection of horizontal gene transfer events.
AB  - In recent years, the increase in the amounts of available genomic data has made
      it easier to appreciate the extent by which organisms increase their genetic
      diversity through horizontally transferred genetic material. Such transfers have
      the potential to give rise to extremely dynamic genomes where a significant
      proportion of their coding DNA has been contributed by external sources. Because
      of the impact of these horizontal transfers on the ecological and pathogenic
      character of the recipient organisms, methods are continuously sought that are
      able to computationally determine which of the genes of a given genome are
      products of transfer events. In this paper, we introduce and discuss a novel
      computational method for identifying horizontal transfers that relies on a gene's
      nucleotide composition and obviates the need for knowledge of codon boundaries.
      In addition to being applicable to individual genes, the method can be easily
      extended to the case of clusters of horizontally transferred genes. With the help
      of an extensive and carefully designed set of experiments on 123 archaeal and
      bacterial genomes, we demonstrate that the new method exhibits significant
      improvement in sensitivity when compared to previously published approaches. In
      fact, it achieves an average relative improvement across genomes of between 11
      and 41% compared to the Codon Adaptation Index method in distinguishing native
      from foreign genes. Our method's horizontal gene transfer predictions for 123
      microbial genomes are available online at http://cbcsrv.watson.ibm.com/HGT/.

PMID- 15716311
TI  - Long-range oscillation in a periodic DNA sequence motif may influence nucleosome
      array formation.
AB  - We have experimentally examined the characteristics of nucleosome array formation
      in different regions of mouse liver chromatin, and have computationally analyzed
      the corresponding genomic DNA sequences. We have shown that the mouse adenosine
      deaminase (MADA) gene locus is packaged into an exceptionally regular nucleosome
      array with a shortened repeat, consistent with our computational prediction based
      on the DNA sequence. A survey of the mouse genome indicates that <10% of 70 kb
      windows possess a nucleosome-ordering signal, consisting of regular long-range
      oscillations in the period-10 triplet motif non-T, A/T, G (VWG), which is as
      strong as the signal in the MADA locus. A strong signal in the center of this
      locus, confirmed by in vitro chromatin assembly experiments, appears to cooperate
      with weaker, in-phase signals throughout the locus. In contrast, the mouse
      odorant receptor (MOR) locus, which lacks locus-wide signals, was representative
      of approximately 40% of the mouse genomic DNA surveyed. Within this locus,
      nucleosome arrays were similar to those of bulk chromatin. Genomic DNA sequences
      which were computationally similar to MADA or MOR resulted in MADA- or MOR-like
      nucleosome ladders experimentally. Overall, we provide evidence that
      computationally predictable information in the DNA sequence may affect nucleosome
      array formation in animal tissue.

PMID- 15716312
TI  - Protein coding potential of retroviruses and other transposable elements in
      vertebrate genomes.
AB  - We suggest an annotation strategy for genes encoded by retroviruses and
      transposable elements (RETRA genes) based on a set of marker protein domains.
      Usually RETRA genes are masked in vertebrate genomes prior to the application of
      automated gene prediction pipelines under the assumption that they provide no
      selective advantage to the host. Yet, we show that about 1000 genes in four
      vertebrate gene sets analyzed contain at least one RETRA gene marker domain.
      Using the conservation of genomic neighborhood (synteny), we were able to
      discriminate between RETRA genes with putative functionality in the vertebrates
      and those that probably function only in the context of mobile elements. We
      identified 35 such genes in human, along with their corresponding mouse and rat
      orthologs; which included almost all known human genes with similarity to mobile
      elements. The results also imply that the vast majority of the remaining RETRA
      genes in current gene sets are unlikely to encode vertebrate functions. To
      automatically annotate RETRA genes in other vertebrate genomes, we provide as a
      tool a set of marker protein domains and a manually refined list of domesticated
      or ancestral RETRA genes for rescuing genes with vertebrate functions.

PMID- 15716313
TI  - mRNA sequence features that contribute to translational regulation in
      Arabidopsis.
AB  - DNA microarrays were used to evaluate the regulation of the proportion of
      individual mRNA species in polysomal complexes in leaves of Arabidopsis thaliana
      under control growth conditions and following a mild dehydration stress (DS). The
      analysis determined that the percentage of an individual gene transcript in
      polysomes (ribosome loading) ranged from over 95 to <5%. DS caused a decrease in
      ribosome loading from 82 to 72%, with maintained polysome association for over
      60% of the mRNAs with an increased abundance. To identify sequence features
      responsible for translational regulation, ribosome loading values and features of
      full-length mRNA sequences were compared. mRNAs with extreme length or high GU
      content in the 5'-untranslated regions (5'-UTRs) were generally poorly
      translated. Under DS, mRNAs with both a high GC content in the 5'-UTR and long
      open reading frame showed a significant impairment in ribosome loading.
      Evaluation of initiation A+1UG codon context revealed distinctions in the
      frequency of adenine in nucleotides -10 to -1 (especially at -4 and -3) in mRNAs
      with different ribosome loading values. Notably, the mRNA features that
      contribute to translational regulation could not fully explain the variation in
      ribosome loading, indicating that additional factors contribute to translational
      regulation in Arabidopsis.

PMID- 15716314
TI  - Evaluation of exhalation valves.
AB  - Certification tests currently employed by some industrialized nations to certify
      respirators require that when challenged with air flow at a constant suction head
      of 25 mmH2O, the leakage into the facepiece from the exhalation valve(s) should
      not exceed 30 ml min(-1). However, the test alone might not reflect the leakage
      rate under different levels of vacuum. To study the characteristics of leakage
      through exhalation valves, a leakage meter was built to measure the leakage rate
      of four brands of exhalation valves. Seven valves of each brand were tested for
      leakage rate at pressure drops ranging from 15 to 45 mmH2O (or extended to 75
      mmH2O for some valves). Two types of leaks, i.e. fiber insertion and arch dent on
      the valve seat, were used to investigate the effect of leak shape on the
      characteristic leak flow as a function of pressure drop. A leakage data point
      represented a mean value of five measurements. The results showed that the
      leakage rate could increase or decrease with increasing pressure drop inside the
      respirators, indicating that the current method of conducting leakage tests, at a
      constant suction head of 25 mmH2O, does not guarantee better protection than when
      the respirators are used at a lower suction head. Moreover, based on the sample
      valves tested in this study, it was found that valve leakage was mostly caused by
      defects in the valve seats. Both fiber-insertion and arch-dent leaks had either
      increasing or decreasing characteristic curves, depending on the size of the leak
      and the material of the valve membrane.

PMID- 15716315
TI  - Evaluation of interstitial lung disease in mixed connective tissue disease
      (MCTD).
AB  - OBJECTIVE: Interstitial lung disease (ILD) may be a characteristic, often
      serious, manifestation of mixed connective tissue disease (MCTD). In this
      retrospective study, the frequency and clinical picture of ILD were determined in
      patients with MCTD using two diagnostic tests: high-resolution computed
      tomography (HRCT) and inhaled aerosol clearance times of (99m)Tc-labelled
      diethylene-triamine pentaacetate ((99m)Tc-DTPA). In addition, pulmonary function,
      effects of therapy and a variety of immunoserological markers were also assessed.
      METHODS: One hundred and forty-four consecutive patients with MCTD were selected
      from the clinic, irrespective of the presence or absence of ILD. All patients
      underwent a detailed clinical assessment, chest HRCT scanning, chest radiography,
      inhaled aerosol of (99m)Tc-DTPA clearance times, and all pulmonary function
      tests. Patients who had active ILD received corticosteroid (CS) or CS in
      combination with cyclophosphamide (CPH). All investigations were repeated after 6
      months of immunosuppressive therapy. RESULTS: Ninety-six out of 144 MCTD patients
      (66.6%) had active ILD, 75 of this group (78.1%) showed ground glass opacity, 21
      patients (21.8%) ground glass opacity with mild fibrosis with HRCT. Forty-five
      patients with active ILD received 2 mg/kg/day CS for 6-8 weeks alone and 51
      patients CS in combination with CPH (2 mg/kg/day). Six months later, after
      therapy, 67 out of 96 MCTD patients with ILD (69.8%) showed a negative HRCT
      pattern, ground glass opacity with mild fibrosis developed in 15 patients
      (15.6%), and fibrosis was detected in 13 patients (13.5%). Only one patient
      showed subpleural honeycombing. (99m)Tc-DTPA was rapid in all 96 MCTD patients
      with active ILD (28.7 +/- 8.2 min, normal value >40 min). After therapy the
      (99m)Tc-DTPA was normalized, 79 out of 96 patients (82.3%). Carbon monoxide
      diffusion capacity (DLCO) was reduced in 33 out of 96 MCTD patients with active
      ILD (34.3%), while there were no significant differences in the pulmonary
      function tests between the active versus inactive stage of ILD or versus patients
      without ILD. The sera of 96 MCTD patients with active ILD contained a high level
      of immune complexes (ICs), and the total haemolytic complement levels (CH50/ml U)
      decreased. After 6 months of therapy, the IC levels decreased and CH50/ml levels
      normalized (MCTD patients before and after active ILD: IC optical density = 355
      +/- 227 vs 206 +/- 92, P<0.001; CH50/ml, 38.0 +/- 12.6 U vs 64.3 +/- 13.0 U,
      P<0.001). CONCLUSIONS: HRCT is the gold standard for diagnosis of ILD. However,
      we used another method, (99m)Tc-DTPA, in order to compare this technique with
      HRCT. This latter technique has not been studied previously in MCTD. The elevated
      levels of IC and increased complement consumption indicated that IC-mediated
      alveolocapillary membrane damage and tissue injury might play a role in the
      pathogenesis of ILD in MCTD.

PMID- 15716316
TI  - Paediatric rheumatology: a bright future in the UK and Europe.

PMID- 15716317
TI  - Clinical characteristics of an anatomical hand index measured in patients with
      rheumatoid arthritis as a potential outcome measure.
AB  - OBJECTIVES: To determine the clinical characteristics of an anatomical hand index
      previously reported as a potential measure of joint deformity and outcome in
      patients with rheumatoid arthritis. METHODS: The hand index (open hand span -
      closed hand span/lateral height of the hand) was measured in a cross-sectional
      study of 145 out-patients with rheumatoid arthritis with disease durations 0-55
      yr. Subsets of patients were restudied at mean follow-ups of approximately 9
      months and 4 yr. RESULTS: The hand index fell gradually with disease duration.
      Correlations were demonstrated with the Sharp index (r = - 0.39, P = 0.000) and
      to a lesser extent with disease activity score (r = - 0.28, P = 0.001). At 260 +/
      115 days the hand index worsened by 0.09 units (P = 0.09, NS). At 51.6 +/- 5.4
      months the index showed a fall from 1.96 +/- 0.73 to 1.61 +/- 0.65 (P = 0.000).
      During the same interval the Sharp index increased from 60 +/- 68 to 80 +/- 71 (P
      = 0.000). CONCLUSIONS: Measurement of simple hand dimensions can demonstrate
      worsening of hand deformity with time in patients with rheumatoid arthritis. We
      suggest that more sophisticated analysis of digital hand images, as used in our
      original study, might yield additional information and increase the sensitivity
      of an anatomical hand index as an outcome measure in rheumatoid arthritis.

PMID- 15716318
TI  - Corneodesmosin polymorphisms in psoriatic arthritis.

PMID- 15716320
TI  - Predictive and potentially predictive factors in early arthritis: a
      multidisciplinary approach.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is characterized by variable degrees of
      joint inflammation, joint destruction, progressive disability and premature
      death. Destruction of joint cartilage and bone may occur early during disease, as
      was shown in longitudinal studies of RA, and there is increasing consent among
      rheumatologists that early diagnosis and early initiation of therapy with disease
      modifying anti-rheumatic drugs (DMARDs) can limit the severity of RA.
      Unfortunately, the currently used diagnostic and predictive indicators (clinical,
      laboratory and radiological) are of limited value for making an early diagnosis
      and prognosis of the disease course at the individual level, thus reducing
      optimal benefit from present and emerging therapies. Therefore, this review
      focuses on the multidisciplinary aspects of neuroendocrine-immune changes in RA.
      METHODS: A Medline search was performed using the search terms 'androgens',
      'estrogens', 'sympathetic nervous system', 'sensory nervous system', 'prognosis',
      'early rheumatoid arthritis', 'arthritis' and 'studies' in various combinations.
      For the tabular overview, we only listed clinical studies focusing on endocrine
      and neuronal aspects. RESULTS: In addition to the currently used predictive
      indicators, there is an abundant body of literature describing changes of the
      neuronal, endocrine and immune parameters during inflammatory diseases.
      Unfortunately, no longitudinal studies concerning neuroendocrine aspects have
      been done up to now. CONCLUSION: Parameters of the neuroendocrine system should
      be included in anticipated longitudinal clinical studies to find their true
      predictive value in early RA.

PMID- 15716321
TI  - Giant cell arteritis and polymyalgia rheumatica: usefulness of vascular magnetic
      resonance imaging studies in the diagnosis of aortitis.
AB  - OBJECTIVES: One of the unresolved challenges posed in giant cell (temporal)
      arteritis (GCA) is the detection and monitoring of large-artery complications,
      particularly aortitis. Recent investigations support vascular magnetic resonance
      imaging (MRI) studies in this issue. We report our preliminary experience with
      this imaging technique in the study of the aorta and its proximal branches in
      patients with GCA and/or polymyalgia rheumatica (PMR). METHODS: Between 2000 and
      2003, six patients with GCA and/or PMR seen in our department were diagnosed with
      aortitis using vascular MRI studies. In all cases, the study was performed
      according to a specifically designed protocol that included MRI and MR
      angiography (MRA). RESULTS: MRI was a hepful non-invasive method for diagnosis of
      aortitis in all cases, providing accurate information about its extent. In
      particular, MRI had a higher ability to detect earlier stages of vasculitis
      disclosing subclinical aortitis in five of the six patients. The main signs of
      early vascular inflammation observed were vessel wall thickness and oedema (six
      cases) and increased mural enhancement on postcontrast T1-weighted images (four
      cases). MRA disclosed lumen changes (stenosis) in two patients. On follow-up
      studies, whereas vascular stenosis and vessel wall thickness remained invariable,
      vascular wall oedema and contrast enhancement improved significantly when disease
      activity decreased. CONCLUSION: MRI may be a useful technique for diagnosing
      patients with occult major artery involvement in GCA, whether presenting with
      classic symptoms of temporal arteritis or PMR. Its utility for monitoring the
      course of the disease and response to treatment requires further confirmation.

PMID- 15716322
TI  - Referrals to hospital-based rheumatology and orthopaedic services: seeking
      direction.
AB  - OBJECTIVES: While both community and hospital-based services strive to cope with
      the considerable burden posed by musculoskeletal disorders, multidisciplinary
      led, integrated approaches are frequently lacking. It has been suggested that
      referrals to musculoskeletal services are frequently misdirected to an
      orthopaedic surgeon when non-surgical advice/intervention is warranted, reducing
      the efficiency of hospital-based services and potentially affecting quality of
      care. Triage of referrals may help to prevent this, but this system is dependent
      upon accurate and thorough information being provided in the referral letter. Our
      aim was to assess the feasibility of triage of musculoskeletal referrals to
      rheumatology and orthopaedic services at a large teaching hospital. METHODS: One
      thousand and eighty-seven consecutive referral letters to orthopaedic and
      rheumatology services were reviewed by a consultant rheumatologist. Letters were
      assessed for both basic content and the appropriate destination for that
      referral. In order to evaluate the accuracy of the assessor's prediction of the
      most appropriate destination of the referrals, the number of patients who were
      ultimately listed for surgical intervention was calculated in a random sample of
      orthopaedic referrals, 1 yr after the initial hospital appointment was requested.
      RESULTS: Six hundred and eighty-two referrals were to orthopaedics and 393 to
      rheumatology. Referrals relating to spinal pain were excluded. The content of
      letters was scant and no diagnosis was volunteered in 63.4% of referrals. Fifty
      eight per cent of referrals to orthopaedics were considered appropriate; 27% of
      referrals to orthopaedics were defined as 'should definitely see a
      rheumatologist' (12%) or 'should probably see a rheumatologist' (15%). Fifteen
      per cent of referrals to orthopaedics were defined as 'could see either a surgeon
      or a rheumatologist'. Ninety-four per cent of referrals to rheumatology were
      defined as appropriate, 2% were not and 4% were defined as 'could see either a
      surgeon or a rheumatologist'. One year later, in a random sample of 373 of the
      orthopaedic referrals, 42.2% of those who were categorized as 'should see
      surgeon' and 9.7% of the 'should see a physician' group were listed for surgical
      intervention. CONCLUSIONS: Many referrals to hospital-based musculoskeletal
      services are likely to be misdirected. Integrated referral and care pathways are
      required for efficient and optimal care of patients with musculoskeletal
      diseases. The development of such pathways will require significant support,
      education and training for general practitioners.

PMID- 15716323
TI  - Expression of the unconventional myosin Myo1c alters sodium transport in M1
      collecting duct cells.
AB  - Epithelial cells rely on proper targeting of cellular components to perform their
      physiological function. This dynamic process utilizes the cytoskeleton and
      involves movement of vesicles to and from the plasma membrane, thus traversing
      the actin cortical cytoskeleton. Studies support both direct interaction of actin
      with channels and an indirect mechanism whereby actin may serve as a track in the
      final delivery of the channel to the plasma membrane. Actin-dependent processes
      are often mediated via a member of the myosin family of proteins. Myosin I family
      members have been implicated in multiple cellular events occurring at the plasma
      membrane. In these studies, we investigated the function of the unconventional
      myosin I Myo1c in the M1 mouse collecting duct cell line. Myo1c was observed to
      be concentrated at or near the plasma membrane, often in discrete membrane
      domains. To address the possible role of Myo1c in channel regulation, we
      expressed a truncated Myo1c, lacking ATP and actin domains, in M1 cells and
      compared electrophysiological responses to control M1 cells, M1 cells expressing
      the empty vector, and M1 cells expressing the full-length Myo1c construct.
      Interestingly, cells expressing the Myo1c constructs had modulated antidiuretic
      hormone (ADH)-stimulated short-circuit current and showed little inhibition of
      short-circuit current with amiloride addition. Evaluation of enhanced green
      fluorescent protein-Myo1c constructs supports the importance of the IQ region in
      targeting the Myo1c to its respective cellular domain. These data are consistent
      with Myo1c participating in the regulation of the Na+ channel after ADH
      stimulation.

PMID- 15716324
TI  - Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle
      regeneration.
AB  - Skeletal muscle possesses a remarkable capacity for regeneration. Although the
      regulation of this process at the molecular level remains largely undefined, the
      plasminogen system appears to play a critical role. Specifically, mice deficient
      in either urokinase-type plasminogen activator (uPA-/- mice) or plasminogen
      demonstrate markedly impaired muscle regeneration after injury. In the present
      study, we tested the hypothesis that loss of the primary inhibitor of uPA,
      plasminogen activator inhibitor-1 (PAI-1), would improve muscle regeneration.
      Repair of the extensor digitorum longus muscle was assessed after cardiotoxin
      injury in wild-type, uPA-/-, and PAI-1-deficient (PAI-1-/-) mice. As expected,
      there was no uPA activity in the injured muscles of uPA-/- mice, and muscles from
      these transgenic animals demonstrated impaired regeneration. On the other hand,
      uPA activity was increased in injured muscle from PAI-1-/- mice to a greater
      extent than in wild-type controls. Furthermore, PAI-1-/- mice demonstrated
      increased expression of MyoD and developmental myosin after injury as well as
      accelerated recovery of muscle morphology, protein levels, and muscle force
      compared with wild-type animals. The injured muscles of PAI-1-null mice also
      demonstrated increased macrophage accumulation, contrasting with impaired
      macrophage accumulation in uPA-deficient mice. The extent of macrophage
      accumulation correlated with both the clearance of protein after injury and the
      efficiency of regeneration. Taken together, these results indicate that PAI-1
      deficiency promotes muscle regeneration, and this protease inhibitor represents a
      therapeutic target for enhancing muscle regeneration.

PMID- 15716325
TI  - TNF-alpha-mediated apoptosis in vascular smooth muscle cells requires p73.
AB  - Atherosclerosis, now considered an inflammatory process, is the leading cause of
      death in the Western world and is manifested by a variety of diseases in multiple
      organ systems. Because of its prevalence and associated morbidity, novel
      therapies directed at arresting this progressive process are urgently needed. The
      inflammatory mediator TNF-alpha, which is known to contribute to apoptosis in
      vascular smooth muscle cells, has been shown to be intimately involved in the
      atherosclerotic process, being present at elevated levels in human atheroma as
      well as possibly being responsible for plaque rupture, a clinically devastating
      event. In light of our earlier finding that p73 is a proapoptotic protein in
      vascular smooth muscle cells, which are involved in plaque progression as well as
      rupture, we asked whether TNF-alpha mediates apoptosis in these cells through
      p73. We now show that p73 is present in spindle-shaped cells within human
      atheroma, and p73beta, an isoform that is pivotal in both apoptosis and growth
      suppression, is induced in vascular smooth muscle cells in vitro by serum but not
      by PDGF-BB. In addition, TNF-alpha, when added to these cells in the presence of
      serum-containing media, increases p73beta expression and causes apoptosis in both
      rat and human vascular smooth muscle cells. Inhibition of p73 activity with a
      dominant inhibitory NH2-terminally deleted p73 plasmid results in markedly
      decreased TNF-alpha-induced apoptosis. Thus p73beta is likely a mediator of the
      apoptotic effect of TNF-alpha in the vasculature, such that future targeting of
      the p73 isoforms may ultimately prove useful in novel atherosclerosis therapies.

PMID- 15716326
TI  - ROK-induced cross-link formation stiffens passive muscle: reversible strain
      induced stress softening in rabbit detrusor.
AB  - Passive mechanical properties of strips of rabbit detrusor smooth muscle were
      examined and found by cyclic loading in a calcium-free solution to display
      viscoelastic softening and strain-induced stress softening (strain softening).
      Strain softening, or the Mullins effect, is a loss of stiffness attributed to the
      breakage of cross-links, and appeared irreversible in detrusor even after the
      return of spontaneous rhythmic tone during 120 min of incubation in a calcium
      containing solution. However, 3 min of KCl or carbachol (CCh)-induced contraction
      permitted rapid regeneration of the passive stiffness lost to strain softening,
      and 3 microM of the RhoA kinase (ROK) inhibitor Y-27632 prevented this
      regeneration. The degree of ROK-induced passive stiffness was inversely dependent
      on muscle length over a length range where peak CCh-induced force was length
      independent. Thus rabbit detrusor displayed variable passive stiffness both
      strain- and activation-history dependent. In conclusion, activation of ROK by KCl
      or CCh increased passive stiffness softened by muscle strain and thereby
      attributed to cross-links that remained stable during tissue incubation in a
      calcium-free solution. Degradation of this signaling system could potentially
      contribute to urinary incontinence.

PMID- 15716327
TI  - Concentrations of cyclosporin A and FK506 that inhibit IL-2 induction in human T
      cells do not affect TGF-beta1 biosynthesis, whereas higher doses of cyclosporin A
      trigger apoptosis and release of preformed TGF-beta1.
AB  - Cyclosporin A (CsA) and FK506 suppress T cell activation by inhibiting
      calcineurin and the calcineurin-dependent transcription factors nuclear factor of
      activated T cells (NFATc), which are central regulators of T cell function. It
      was reported that CsA up-regulated the transcription of transforming growth
      factor-beta1 (TGF-beta1) in lymphocytes and other cells and activated its
      promoter in A549 lung carcinoma cells, but the mechanisms involved are poorly
      understood, and it is unclear whether calcineurin plays any role. We have studied
      the regulation of TGF-beta1 in normal human lymphocytes and cell lines. In Jurkat
      T cells, the TGF-beta1 promoter was activated by calcineurin and NFATc and
      inhibited by CsA and FK506. However, the promoter was insensitive to both drugs
      in A549 cells. In human T cells preactivated with phytohemagglutinin,
      biosynthesis of TGF-beta1, induced by the T cell receptor (TCR) or the TGF-beta
      receptor, was not substantially affected by CsA and FK506 concentrations (< or =
      1 microM) that effectively inhibited interleukin-2 production. However,
      pretreatment of fresh lymphocytes with CsA or FK506 during primary TCR
      stimulation reduced their production of TGF-beta1 during secondary TCR
      activation. Finally, high concentrations of CsA (10 microM), in the range
      attained in vivo in experiments in rodents, caused apoptosis in human T cells and
      the release of preformed, bioactive TGF-beta1. These effects are unlikely to owe
      to calcineurin inhibition, as they were not observed with FK506. Our results
      indicate that CsA and FK506 are not general inducers of TGF-beta1 biosynthesis
      but can cause different effects on TGF-beta1 depending on the cell type and
      concentrations used.

PMID- 15716328
TI  - Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient
      mice with Alport disease.
AB  - Human Alport disease is caused by a lack of the alpha3-, 4-, or 5-chain of type
      IV collagen (COL4A). Affected humans and COL4A3-deficient mice develop
      glomerulosclerosis and progressive renal fibrosis in the presence of interstitial
      macrophages, but their contribution to disease progression is under debate. This
      question was addressed by treating COL4A3-deficient mice with BX471, an
      antagonist of chemokine receptor 1 (CCR1) that is known to block interstitial
      leukocyte recruitment. Treatment with BX471 from weeks 6 to 10 of life improved
      survival of COL4A3-deficient mice, associated with less interstitial macrophages,
      apoptotic tubular epithelial cells, tubular atrophy, interstitial fibrosis, and
      less globally sclerotic glomeruli. BX471 reduced total renal Cll5 mRNA expression
      by reducing the number of interstitial CCL5-positive cells in inflammatory cell
      infiltrates. Intravital microscopy of the cremaster muscle in male mice
      identified that BX471 or lack of CCR1 impaired leukocyte adhesion to activated
      vascular endothelium and transendothelial leukocyte migration, whereas leukocyte
      rolling and interstitial migration were not affected. Furthermore, in activated
      murine macrophages, BX471 completely blocked CCL3-induced CCL5 production. Thus,
      CCR1-mediated recruitment and local activation of macrophages contribute to
      disease progression in COL4A3-deficient mice. These data identify CCR1 as a
      potential therapeutic target for Alport disease or other progressive
      nephropathies associated with interstitial macrophage infiltrates.

PMID- 15716329
TI  - Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance
      in patients with type 2 diabetes.
AB  - Increased (intra)renal activity of the renin-angiotensin system may cause a
      persistent increase in renovascular resistance and intraglomerular pressure in
      patients with diabetes, thus contributing to the development of diabetic renal
      damage. The effect of chronic angiotensin II subtype 1 receptor blockade on
      (intra)renal hemodynamics in patients with type 2 diabetes was examined in a
      double-blind parallel group study. Patients were treated with 40 mg of olmesartan
      (n = 19) or placebo (n = 16), and renal hemodynamics were assessed before and
      after 12 wk of treatment using inulin and para-aminohippurate clearance
      techniques. Olmesartan significantly reduced 24-h ambulatory systolic and
      diastolic BP (both P < 0.05). In parallel, effective renal plasma flow increased
      significantly from 602 +/- 76 to 628 +/- 87 ml/min per 1.73 m(2), whereas
      filtration fraction and renovascular resistance decreased significantly (all P <
      0.05). With placebo treatment, effective renal plasma flow decreased and
      filtration fraction increased significantly (both P < 0.05). GFR was not affected
      by both treatments. Active plasma renin concentration increased considerably (P <
      0.05) with olmesartan therapy but remained unchanged with placebo treatment.
      Nitric oxide metabolism (plasma nitrate and nitrite) and asymmetric
      dimethylarginine blood levels were not affected by olmesartan and placebo
      therapy. In contrast, plasma 8-isoprostane 15(S)-8-iso-prostaglandin F(2a)
      concentration, a biochemical marker of oxidative stress, decreased significantly
      (P < 0.05) with olmesartan treatment. Chronic angiotensin II subtype 1 receptor
      blockade decreases (intra)renal vascular resistance and increases renal perfusion
      despite significant BP reduction. In addition, it significantly reduces oxidative
      stress. These effects of angiotensin II receptor antagonists may contribute to
      their beneficial long-term renal effects in patients with type 2 diabetes.

PMID- 15716330
TI  - Role of ERK1/2 and p38 mitogen-activated protein kinases in the regulation of
      thrombospondin-1 by TGF-beta1 in rat proximal tubular cells and mouse
      fibroblasts.
AB  - Thrombospondin-1 (TSP-1) inhibits angiogenesis and activates latent TGF-beta1,
      both of which are strongly associated with progression of renal disease.
      Recently, it was reported that Smad2 but not Smad3 regulates TSP-1 expression in
      response to TGF-beta1 in rat tubular epithelial cells as well as in mouse
      fibroblasts. This study investigated the role of ERK1/2 and p38 mitogen-activated
      protein kinases (MAPK). TGF-beta1 activated both ERK1/2 and p38 in the rat
      proximal tubular cell line NRK52E. Blocking ERK1/2 and p38 inhibited TGF-beta1
      induced TSP-1 mRNA and protein expression. Next, the cross-talk between Smad2 and
      ERK1/2 or p38 was examined. Whereas blocking of ERK1/2 or p38 failed to inhibit
      TGF-beta1-induced Smad2 activation, inhibition of Smad2 by Smad7 overexpression
      inhibited the phosphorylation of ERK1/2 but not p38 in response to TGF-beta1.
      Similar results were observed using mouse fibroblasts from Smad2 knockout
      embryos, in that TGF-beta1 was able to activate p38 but not ERK1/2 in this cell
      line. In conclusion, TSP-1 expression is regulated by both ERK1/2 and p38 MAPK in
      rat proximal tubular cells and mouse fibroblasts in response to TGF-beta1. The
      ERK1/2 activation is dependent on Smad2 activation, whereas the p38 activation
      occurs independent of Smad2. Because TSP-1 is a major antiangiogenic molecule and
      an activator of TGF-beta1, this provides an important insight to the mechanism by
      which TGF-beta1 may mediate interstitial fibrosis and progressive renal disease.

PMID- 15716331
TI  - Effects of proteasome inhibition on the kidney in experimental
      hypercholesterolemia.
AB  - Hypercholesterolemia (HC) and atherosclerosis often accompany and aggravate renal
      disease. Proteasome inhibitors (PSI) can decrease proliferation and inflammation,
      likely by reducing activation of the proinflammatory NF-kappaB. However, chronic
      proteasome inhibition has never been demonstrated in the HC kidney. Four groups
      of pigs (n = 7 each) were studied after a 12-wk normal (N) or 2% HC diet alone or
      supplemented (N+PSI and HC+PSI) with MLN-273 (0.08 mg/kg subcutaneously twice
      weekly). Renal hemodynamics and function were quantified in vivo using electron
      beam computed tomography at baseline and after vasodilator challenge using
      acetylcholine. Renal tissue was studied ex vivo using immunoblotting, PCR, and
      immunohistochemistry. Serum cholesterol was similarly elevated in HC and HC+PSI.
      Basal renal blood flow was similar among the groups, whereas GFR was decreased in
      both N+PSI and HC+PSI. The blunted renovascular and functional responses to
      acetylcholine in HC were normalized in HC+PSI (suggesting renal endothelial
      function improvement), which was accompanied by decreased renal endothelin, NF
      kappaB, and augmented endothelial nitric oxide synthase expression. In parallel,
      HC+PSI animals also showed elevated NAD(P)H oxidase expression and circulating
      oxidized LDL, suggesting a potential for increased oxidative stress. This study
      shows that chronic PSI intervention in HC improves renal endothelial functional
      responses to challenge, possibly by modulating nitric oxide availability and
      endothelin. Furthermore, PSI may decrease intrarenal inflammation through
      modulation of the NF-kappaB pathway but may potentially increase oxidative
      stress, which warrants further investigation. This study may support a role for
      the ubiquitin/proteasome system in the kidney in HC and early atherosclerosis.

PMID- 15716332
TI  - In vivo modulation of soluble "antagonistic" IL-6 receptor synthesis and release
      in ESRD.
AB  - Soluble gp130 (sgp130) is a soluble circulating receptor of IL-6 with
      "antagonistic" biologic activity. It is generated independently by either
      shedding of the extracellular domain of membrane gp130 or alternative mRNA
      splicing. This study was addressed to clarify the mechanisms underlying sgp130
      synthesis and release in patients who undergo regular dialysis treatment (RDT)
      using dialytic membranes with different biocompatibility. Two groups of RDT
      patients were enrolled: 11 patients who were treated with cellulosic membranes
      (C) and 10 patients who were treated with synthetic membranes (S). Ten healthy
      subjects constituted the control group. Serum samples and peripheral blood
      mononuclear cells (PBMC) were harvested in all groups (before dialysis in RDT
      patients). PBMC were cultured for 24 h in the absence or presence of LPS. The
      serum levels of sgp130 were significantly higher in C group than in control and S
      patients (C, 603.1 +/- 89.9; control, 396 +/- 49.5; S, 423.4 +/- 27.7 ng/ml; P <
      0.01). PBMC from C patients, in the absence of any mitogenic stimulation,
      released a significantly greater amount of sgp130 as compared with S and control
      groups (C, 532.6 +/- 161.2; S, 332.4 +/- 148.6; control, 341.4 +/- 125.4 pg/ml; P
      < 0.01). The sgp130 release was positively correlated with the release of both IL
      6 (r = 0.336, P < 0.05) and sIL-6R receptor (r = 0.324, P < 0.05). A
      significantly higher gp130 gene expression was also observed in unstimulated PBMC
      from C patients when compared with control and S groups. It is interesting that
      the expression of the 85-bp exon characteristic of the alternative splicing mRNA
      for sgp130 was low in all groups. Finally, confocal microscopy analysis showed an
      increased expression of gp130 on cell surface in unstimulated PBMC from C
      patients as compared with control and S groups. Our results demonstrate that in
      patients on RDT with C membranes, the synthesis and release of sgp130
      "antagonistic" receptor is significantly increased. This release is seemingly due
      to a shedding of membrane-bound gp130 receptor. The increased sgp130 release may
      partially counteract the inflammatory effects caused by IL-6.

PMID- 15716333
TI  - Does hemodialysis increase protein breakdown? Dissociation between whole-body
      amino acid turnover and regional muscle kinetics.
AB  - Hemodialysis (HD) is a protein catabolic procedure. Whole-body amino acid
      turnover studies identify dialysate amino acid loss and reduced protein synthesis
      as the catabolic events; proteolysis is not increased. Regional amino acid
      kinetics, however, document enhanced muscle protein breakdown as the cause of the
      catabolism; muscle protein synthesis also increased but to a lesser magnitude
      than the increment in protein breakdown. This discordance between whole-body and
      regional kinetics is best explained by the contrasting physiology between the
      muscle and the liver. During HD, muscle releases amino acids, which then are
      taken up by the liver for de novo protein synthesis. There seems to be a somatic
      to visceral recycling of amino acids. Evidence supporting this concept includes
      the increased fractional synthesis of albumin and fibrinogen during HD. It should
      be emphasized that region- or organ-specific kinetics vary, and whole-body
      turnover is a composite of all of the visceral and somatic compartments taken
      together. Reduced whole-body protein synthesis may be a compensatory adaptation
      to dialysate amino acid loss with a consequent reduction in plasma amino acid
      concentration. Notwithstanding the protein catabolic nature of HD, evidence is
      accumulating that intradialytic nutritional supplementation may blunt its
      catabolic effect.

PMID- 15716334
TI  - Focal and segmental glomerulosclerosis: definition and relevance of a partial
      remission.
AB  - Focal and segmental glomerulosclerosis (FSGS) is one of the most common primary
      glomerular diseases to terminate in ESRD. A complete remission (CR) confers an
      excellent long-term prognosis, but the quantitative benefits of partial
      remissions (PR) have not been defined. This study evaluated the rate of renal
      function decline (slope of creatinine clearance) and renal survival in nephrotic
      FSGS patients with CR, PR, or no remission. It also examined relapse rate from
      remission and its impact on outcome. Multivariate analysis included clinical and
      laboratory data at presentation and over follow-up, BP control, the agents used,
      and immunosuppressive therapy. The study cohort was 281 nephrotic FSGS patients
      who had a minimum of 12 mo of observation and were identified from the Toronto
      Glomerulonephritis Registry. Over a median follow-up of 65 mo, 55 experienced a
      CR, 117 had a PR, and 109 had no remission. A PR was independently predictive of
      slope and survival from renal failure by multivariate analysis (adjusted time
      dependent hazard ratio, 0.48; 95% confidence interval, 0.24 to 0.96; P = 0.04).
      Immunosuppression with high-dose prednisone was associated with a higher rate of
      PR and CR. Relapse from PR was frequent (56%) and associated with a more rapid
      rate of renal function decline and worse renal survival compared with relapse
      free partial remitters. Only female gender and the nadir of proteinuria during
      remission were associated with a sustained remission. A PR in proteinuria and its
      maintenance are important therapeutic targets in FSGS, with implications for both
      slowing progression rate and improving renal survival.

PMID- 15716335
TI  - Induction and targeting of the glutamine transporter SN1 to the basolateral
      membranes of cortical kidney tubule cells during chronic metabolic acidosis
      suggest a role in pH regulation.
AB  - During chronic metabolic acidosis (CMA), the plasma levels of glutamine are
      increased and so is glutamine metabolism in the kidney tubule cells. Degradation
      of glutamine results in the formation of ammonium (NH(4)(+)) and bicarbonate
      (HCO(3)(-)) ions, which are excreted in the pre-urine and transported to the
      peritubular blood, respectively. This process contributes to counteract acidosis
      and to restore normal pH, but the molecular mechanism, the localization of the
      proteins involved and the regulation of glutamine transport into the renal
      tubular cells, remains unknown. SN1, a Na(+)- and H(+)-dependent glutamine
      transporter has previously been identified molecularly, and its mRNA has been
      detected in tubule cells in the medulla of the kidney. Now shown is the selective
      targeting of the protein to the basolateral membranes of the renal tubule cells
      of the S3 segment throughout development of the normal rat kidney. During CMA,
      SN1 expression increases five- to six-fold and appears also in cortical tubule
      cells in parallel with the increased expression and activity of phosphate
      activated glutaminase, a mitochondrial enzyme involved in ammoniagenesis.
      However, SN1 remains sorted to the basolateral membranes. The unique ability of
      SN1 to change transport direction according to physiologic changes in
      transmembrane gradients of [glutamine] and pH and its sorting to the basolateral
      membranes and the presence of a putative pH responsive element in the 3'
      untranslated region (UTR) of the gene (supported here by the demonstration in CMA
      kidney of a protein that binds SN1 mRNA) are conducive to the function of this
      transporter in pH regulation.

PMID- 15716336
TI  - An alternative formula to the Cockcroft-Gault and the modification of diet in
      renal diseases formulas in predicting GFR in individuals with type 1 diabetes.
AB  - Chronic kidney disease is currently on the rise and not only leads to ESRD
      necessitating dialysis or transplantation but also increases cardiovascular
      disease risk. Measurement of the GFR, the gold standard for assessing kidney
      function, is expensive and cumbersome. Several prediction formulas that are based
      on serum creatinine are currently used to estimate the GFR, but none has been
      validated in a large cohort of individuals with diabetes. The performance of two
      commonly used formulas, the abbreviated Modification of Diet in Renal Disease
      (MDRD) study formula for the GFR and the Cockcroft-Gault estimate of creatinine
      clearance, were examined against GFR measured by the renal clearance of
      iothalamate in 1286 individuals with type 1 diabetes from the Diabetes Control
      and Complications Trial (DCCT). The performance of these formulas was assessed by
      computing bias, precision, and accuracy. The DCCT participants had normal serum
      creatinine, unlike the MDRD patients, and somewhat lower creatinine excretion
      than subjects in the original cohort Cockcroft Gault, which led to biased and
      highly variable estimates of GFR when these formulas were applied to the DCCT
      subjects. The MDRD substantially underestimated iothalamate GFR, whereas the
      Cockcroft Gault formula underestimated it when it was <120 ml/min per 1.73 m(2)
      and overestimated it when iothalamate GFR was >130 ml/min per 1.73 m(2). Overall,
      only one third of the formula's estimates were within +/-10% of iothalamate GFR.
      By underestimating GFR, these formulas were likely to flag early declines in
      kidney function. Refitting the MDRD formula to the DCCT data gave a more accurate
      and unbiased prediction of GFR from serum creatinine; percentage of estimate
      within 10% of measured GFR increased to 56%. A substantial variability in the
      estimates, however, remained.

PMID- 15716337
TI  - Patterning of proneuronal and inter-proneuronal domains by hairy- and enhancer of
      split-related genes in zebrafish neuroectoderm.
AB  - In teleosts and amphibians, the proneuronal domains, which give rise to primary
      motor, primary-inter and Rohon-Beard (RB) neurons, are established at the
      beginning of neurogenesis as three longitudinal stripes along the anteroposterior
      axis in the dorsal ectoderm. The proneuronal domains are prefigured by the
      expression of basic helix-loop-helix (bHLH) proneural genes, and separated by
      domains (inter-proneuronal domains) that do not express the proneural genes.
      Little is known about how the formation of these domains is spatially regulated.
      We have found that the zebrafish hairy- and enhancer of split-related (Her) genes
      her3 and her9 are expressed in the inter-proneuronal domains, and are required
      for their formation. her3 and her9 expression was not regulated by Notch
      signaling, but rather controlled by positional cues, in which Bmp signaling is
      involved. Inhibition of Her3 or Her9 by antisense morpholino oligonucleotides led
      to ectopic expression of the proneural genes in part of the inter-proneuronal
      domains. Combined inhibition of Her3 and Her9 induced ubiquitous expression of
      proneural and neuronal genes in the neural plate, and abolished the formation of
      the inter-proneuronal domains. Furthermore, inhibition of Her3/Her9 and Notch
      signaling led to ubiquitous and homogeneous expression of proneural and neuronal
      genes in the neural plate, revealing that Her3/Her9 and Notch signaling have
      distinct roles in neurogenesis. These data indicate that her3 and her9 function
      as prepattern genes that link the positional dorsoventral polarity information in
      the posterior neuroectoderm to the spatial regulation of neurogenesis.

PMID- 15716338
TI  - The eutardigrade Thulinia stephaniae has an indeterminate development and the
      potential to regulate early blastomere ablations.
AB  - We present a detailed analysis of the cell lineage of the tardigrade Thulinia
      stephaniae with a 4D-microscopy system (3D time-lapse recording). The recording,
      of the entire development from embryogenesis until hatching, allowed us to
      analyze the fate of single descendants from early blastomeres up to germ layer
      formation and tissue development. The embryo undergoes an irregular indeterminate
      cleavage pattern without early fate restriction. During gastrulation, mesodermal
      and endodermal precursors, and a pair of primordial germ cells migrate through a
      blastopore at the prospective position of the mouth. Our results are not
      consistent with earlier descriptions of mesoderm formation by enterocoely in
      tardigrades. The mesoderm in Thulinia stephaniae originates from a variable
      number of blastomeres, which form mesodermal bands that later produce the serial
      somites. The nervous system is formed by neural progenitor cells, which
      delaminate from the neurogenic ectoderm. Early embryogenesis of Thulinia
      stephaniae is highly regulative, even after laser ablations of blastomeres at the
      two- and four-cell stages 'normal' juveniles are formed. This has never been
      observed before for a protostome. Germ cell specification occurs late during
      development between the sixth and seventh cell generation. Comparing the
      development of other protostomes with that of the Tardigrada, which occupy a
      basal position within the Arthropoda, suggests that an indeterminate cleavage and
      regulatory development is not only part of the ground pattern of the Arthropoda,
      but probably of the entire Ecdysozoa.

PMID- 15716339
TI  - Crypt-restricted proliferation and commitment to the Paneth cell lineage
      following Apc loss in the mouse intestine.
AB  - Loss of Apc appears to be one of the major events initiating colorectal cancer.
      However, the first events responsible for this initiation process are not well
      defined and the ways in which different epithelial cell types respond to Apc loss
      are unknown. We used a conditional gene-ablation approach in transgenic mice
      expressing tamoxifen-dependent Cre recombinase all along the crypt-villus axis to
      analyze the immediate effects of Apc loss in the small intestinal epithelium,
      both in the stem-cell compartment and in postmitotic epithelial cells. Within 4
      days, Apc loss induced a dramatic enlargement of the crypt compartment associated
      with intense cell proliferation, apoptosis and impairment of cell migration. This
      result confirms the gatekeeper role of Apc in the intestinal epithelium in vivo.
      Although Apc deletion activated beta-catenin signaling in the villi, we observed
      neither proliferation nor morphological change in this compartment. This
      highlights the dramatic difference in the responses of immature and
      differentiated epithelial cells to aberrant beta-catenin signaling. These
      distinct biological responses were confirmed by molecular analyses, revealing
      that Myc and cyclin D1, two canonical beta-catenin target genes, were induced in
      distinct compartments. We also showed that Apc is a crucial determinant of cell
      fate in the murine intestinal epithelium. Apc loss perturbs differentiation along
      the enterocyte, goblet and enteroendocrine lineages, and promotes commitment to
      the Paneth cell lineage through beta-catenin/Tcf4-mediated transcriptional
      control of specific markers of Paneth cells, the cryptdin/defensin genes.

PMID- 15716340
TI  - Feedback interactions between MKP3 and ERK MAP kinase control scleraxis
      expression and the specification of rib progenitors in the developing chick
      somite.
AB  - Cells in the early vertebrate somite receive cues from surrounding tissues, which
      are important for their specification. A number of signalling pathways involved
      in somite patterning have been described extensively. By contrast, the
      interactions between cells from different regions within the somite are less well
      characterised. Here, we demonstrate that myotomally derived FGFs act through the
      MAPK signal transduction cascade and in particular, ERK1/2 to activate scleraxis
      expression in a population of mesenchymal progenitor cells in the dorsal
      sclerotome. We show that the levels of active, phosphorylated ERK protein in the
      developing somite are crucial for the expression of scleraxis and Mkp3. MKP3 is a
      dual specificity phosphatase and a specific antagonist of ERK MAP kinases and we
      demonstrate that in somites Mkp3 transcription depends on the presence of active
      ERK. Therefore, MKP3 and ERK MAP kinase constitute a negative feedback loop
      activated by FGF in sclerotomal progenitor cells. We propose that tight control
      of ERK signalling strength by MKP3 is important for the appropriate regulation of
      downstream cellular responses including the activation of scleraxis. We show that
      increased or decreased levels of phosphorylated ERK result in the loss of
      scleraxis transcripts and the loss of distal rib development, highlighting the
      importance of the MKP3-ERK-MAP kinase mediated feedback loop for cell
      specification and differentiation.

PMID- 15716341
TI  - Robo2 is required for establishment of a precise glomerular map in the zebrafish
      olfactory system.
AB  - Olfactory sensory neurons (OSNs) expressing a given odorant receptor project
      their axons to specific glomeruli, creating a topographic odor map in the
      olfactory bulb (OB). The mechanisms underlying axonal pathfinding of OSNs to
      their precise targets are not fully understood. Here, we demonstrate that
      Robo2/Slit signaling functions to guide nascent olfactory axons to the OB
      primordium in zebrafish. robo2 is transiently expressed in the olfactory placode
      during the initial phase of olfactory axon pathfinding. In the robo2 mutant,
      astray (ast), early growing olfactory axons misroute ventromedially or
      posteriorly, and often penetrate into the diencephalon without reaching the OB
      primordium. Four zebrafish Slit homologs are expressed in regions adjacent to the
      olfactory axon trajectory, consistent with their role as repulsive ligands for
      Robo2. Masking of endogenous Slit gradients by ubiquitous misexpression of Slit2
      in transgenic fish causes posterior pathfinding errors that resemble the ast
      phenotype. We also found that the spatial arrangement of glomeruli in OB is
      perturbed in ast adults, suggesting an essential role for the initial olfactory
      axon scaffold in determining a topographic glomerular map. These data provide
      functional evidence for Robo2/Slit signaling in the establishment of olfactory
      neural circuitry in zebrafish.

PMID- 15716342
TI  - Vulva morphogenesis involves attraction of plexin 1-expressing primordial vulva
      cells to semaphorin 1a sequentially expressed at the vulva midline.
AB  - Vulva development in C. elegans involves cell fate specification followed by a
      morphogenesis phase in which homologous mirror image pairs within a linear array
      of primordial vulva cells form a crescent shape as they move sequentially towards
      a midline position within the array. The homologous pairs from opposite half
      vulvae in fixed sequence fuse with one another at their leading tips to form ring
      shaped (toroidal) cells stacked in precise alignment one atop the other. Here, we
      show that the semaphorin 1a SMP-1, and its plexin receptor PLX-1, are required
      for the movement of homologous pairs of vulva cells towards this midline
      position. SMP-1 is upregulated on the lumen membrane of each primordial vulva
      cell as it enters the forming vulva and apparently attracts the next flanking
      homologous PLX-1-expressing vulva cells towards the lumen surface of the ring.
      Consequently, a new ring-shaped cell forms immediately ventral to the previously
      formed ring. This smp-1- and plx-1-dependent process repeats until seven rings
      are stacked along the dorsoventral axis, creating a common vulva lumen. Ectopic
      expression of SMP-1 suggests it has an instructive role in vulva cell migration.
      At least two parallel acting pathways are required for vulva formation: one
      requires SMP-1, PLX-1 and CED-10; and another requires the MIG-2 Rac GTPase and
      its putative activator UNC-73.

PMID- 15716343
TI  - FGFR2b signaling regulates ex vivo submandibular gland epithelial cell
      proliferation and branching morphogenesis.
AB  - Branching morphogenesis of mouse submandibular glands is regulated by multiple
      growth factors. Here, we report that ex vivo branching of intact submandibular
      glands decreases when either FGFR2 expression is downregulated or soluble
      recombinant FGFR2b competes out the endogenous growth factors. However, a
      combination of neutralizing antibodies to FGF1, FGF7 and FGF10 is required to
      inhibit branching in the intact gland, suggesting that multiple FGF isoforms are
      required for branching. Exogenous FGFs added to submandibular epithelial
      rudiments cultured without mesenchyme induce distinct morphologies. FGF7 induces
      epithelial budding, whereas FGF10 induces duct elongation, and both are inhibited
      by FGFR or ERK1/2 signaling inhibitors. However, a PI3-kinase inhibitor also
      decreases FGF7-mediated epithelial budding, suggesting that multiple signaling
      pathways exist. We immunolocalized FGF receptors and analyzed changes in FGFR,
      FGF and MMP gene expression to identify the mechanisms of FGF-mediated
      morphogenesis. FGFR1b and FGFR2b are present throughout the epithelium, although
      FGFR1b is more highly expressed around the periphery of the buds and the duct
      tips. FGF7 signaling increases FGFR1b and FGF1 expression, and MMP2 activity,
      when compared with FGF10, resulting in increased cell proliferation and expansion
      of the epithelial bud, whereas FGF10 stimulates localized proliferation at the
      tip of the duct. FGF7- and FGF10-mediated morphogenesis is inhibited by an MMP
      inhibitor and a neutralizing antibody to FGF1, suggesting that both FGF1 and MMPs
      are essential downstream mediators of epithelial morphogenesis. Taken together,
      our data suggests that FGFR2b signaling involves a regulatory network of
      FGFR1b/FGF1/MMP2 expression that mediates budding and duct elongation during
      branching morphogenesis.

PMID- 15716344
TI  - A splice variant of the Wilms' tumour suppressor Wt1 is required for normal
      development of the olfactory system.
AB  - Neuronal lineage formation in the developing olfactory epithelium has been
      extensively studied at the cellular level, but little is known about the genes
      that control proliferation and differentiation of neuronal progenitor cells.
      Here, we report that the Wilms' tumour zinc-finger protein, Wt1, is required for
      normal formation of the olfactory epithelium. Wt1 was detected by
      immunohistochemistry in the developing olfactory epithelium of wild-type embryos
      between gestational days E9.5 and E18.5. Embryos with complete lack of Wt1 and
      embryos with selective ablation of the alternatively spliced Wt1(+KTS) isoform
      both had thinner olfactory epithelia and fewer neuronal progenitor cells than do
      normal animals. Mash1 and neurogenin 1, two basic helix-loop-helix transcription
      factors with critical functions during olfactory neuron development, were reduced
      in the Wt1(+KTS)-/- mutants compared with the wild-type mice. Stable expression
      of the Wt1(+KTS) isoform, but not of the Wt1(-KTS) variant, upregulated Mash1
      mRNA and protein in vitro. The olfactory epithelia of mouse embryos, which lacked
      the Wt1(-KTS) protein, appeared normal. However, formation of the neural retina
      was severely impaired in the Wt1(-KTS)-/- mutants. These findings demonstrate
      that the Wt1(+KTS) protein, which has been proposed to play a role in mRNA
      processing, acts upstream of Mash1 to promote the development of the olfactory
      epithelium. Furthermore, neuron formation depends on distinct functions of
      alternatively spliced Wt1 products in the embryonic retina and the olfactory
      epithelium.

PMID- 15716345
TI  - Nmyc plays an essential role during lung development as a dosage-sensitive
      regulator of progenitor cell proliferation and differentiation.
AB  - Understanding how lung progenitor cells balance proliferation against
      differentiation is relevant to clinical disorders such as bronchopulmonary
      dysplasia of premature babies and lung cancer. Previous studies have established
      that lung development is severely disrupted in mouse mutants with reduced levels
      of the proto-oncogene Nmyc, but the precise mechanisms involved have not been
      explored. We show here that Nmyc expression in the embryonic lung is normally
      restricted to a distal population of undifferentiated epithelial cells, a high
      proportion of which are in the S phase of the cell cycle. Overexpression of
      NmycEGFP in the epithelium under the control of surfactant protein C (Sftpc)
      regulatory elements expands the domain of S phase cells and upregulates numerous
      genes associated with growth and metabolism, as shown by transcriptional
      microarray. In addition, there is marked inhibition of differentiation, coupled
      with an expanded domain of expression of Sox9 protein, which is also normally
      restricted to the distal epithelial compartment. By contrast, conditional
      deletion of Nmyc leads to reduced proliferation, epithelial differentiation and
      high levels of apoptosis in both epithelium and mesenchyme. Unexpectedly, about
      50% of embryos in which only one copy of Nmyc is deleted die perinatally, with
      similarly abnormal lungs. We propose a model in which Nmyc is essential in the
      developing lung for maintaining a distal population of undifferentiated,
      proliferating progenitor cells.

PMID- 15716346
TI  - Distinct functions for Bmp signaling in lip and palate fusion in mice.
AB  - Previous work suggested that cleft lip with or without cleft palate (CL/P) is
      genetically distinct from isolated cleft secondary palate (CP). Mutations in the
      Bmp target gene Msx1 in families with both forms of orofacial clefting has
      implicated Bmp signaling in both pathways. To dissect the function of Bmp
      signaling in orofacial clefting, we conditionally inactivated the type 1 Bmp
      receptor Bmpr1a in the facial primordia, using the Nestin cre transgenic line.
      Nestin cre; Bmpr1a mutants had completely penetrant, bilateral CL/P with arrested
      tooth formation. The cleft secondary palate of Nestin cre; Bmpr1a mutant embryos
      was associated with diminished cell proliferation in maxillary process mesenchyme
      and defective anterior posterior patterning. By contrast, we observed elevated
      apoptosis in the fusing region of the Nestin cre; Bmpr1a mutant medial nasal
      process. Moreover, conditional inactivation of the Bmp4 gene using the Nestin cre
      transgenic line resulted in isolated cleft lip. Our data uncover a Bmp4-Bmpr1a
      genetic pathway that functions in lip fusion, and reveal that Bmp signaling has
      distinct roles in lip and palate fusion.

PMID- 15716347
TI  - thick tassel dwarf1 encodes a putative maize ortholog of the Arabidopsis CLAVATA1
      leucine-rich repeat receptor-like kinase.
AB  - Development in higher plants depends on the activity of meristems, formative
      regions that continuously initiate new organs at their flanks. Meristems must
      maintain a balance between stem cell renewal and organ initiation. In fasciated
      mutants, organ initiation fails to keep pace with meristem proliferation. The
      thick tassel dwarf1 (td1) mutation of maize affects both male and female
      inflorescence development. The female inflorescence, which results in the ear, is
      fasciated, with extra rows of kernels. The male inflorescence, or tassel, shows
      an increase in spikelet density. Floral meristems are also affected in td1
      mutants; for example, male florets have an increase in stamen number. These
      results suggest that td1 functions in the inflorescence to limit meristem size.
      In addition, td1 mutants are slightly shorter than normal siblings, indicating
      that td1 also plays a role in vegetative development. td1 encodes a leucine-rich
      repeat receptor-like kinase (LRR-RLK) that is a putative ortholog of the
      Arabidopsis CLAVATA1 protein. These results complement previous work showing that
      fasciated ear2 encodes a CLAVATA2-like protein, and suggest that the CLAVATA
      signaling pathway is conserved in monocots. td1 maps in the vicinity of
      quantitative trait loci that affect seed row number, spikelet density and plant
      height. We discuss the possible selection pressures on td1 during maize
      domestication.

PMID- 15716348
TI  - Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that
      initiates left-right development of the brain, heart and gut.
AB  - Monocilia have been proposed to establish the left-right (LR) body axis in
      vertebrate embryos by creating a directional fluid flow that triggers asymmetric
      gene expression. In zebrafish, dorsal forerunner cells (DFCs) express a conserved
      ciliary dynein gene (left-right dynein-related1, lrdr1) and form a ciliated
      epithelium inside a fluid-filled organ called Kupffer's vesicle (KV). Here,
      videomicroscopy demonstrates that cilia inside KV are motile and create a
      directional fluid flow just prior to the onset of asymmetric gene expression in
      lateral cells. Laser ablation of DFCs and surgical disruption of KV provide
      direct evidence that ciliated KV cells are required during early somitogenesis
      for subsequent LR patterning in the brain, heart and gut. Antisense morpholinos
      against lrdr1 disrupt KV fluid flow and perturb LR development. Furthermore,
      lrdr1 morpholinos targeted to DFC/KV cells demonstrate that Lrdr1 functions in
      these ciliated cells to control LR patterning. This provides the first direct
      evidence, in any vertebrate, that impairing cilia function in derivatives of the
      dorsal organizer, and not in other cells that express ciliogenic genes, alters LR
      development. Finally, genetic analysis reveals novel roles for the T-box
      transcription factor no tail and the Nodal signaling pathway as upstream
      regulators of lrdr1 expression and KV morphogenesis. We propose that KV is a
      transient embryonic 'organ of asymmetry' that directs LR development by
      establishing a directional fluid flow. These results suggest that cilia are an
      essential component of a conserved mechanism that controls the transition from
      bilateral symmetry to LR asymmetry in vertebrates.

PMID- 15716349
TI  - Ovol1 regulates meiotic pachytene progression during spermatogenesis by
      repressing Id2 expression.
AB  - Previous studies have shown that a targeted deletion of Ovol1 (previously known
      as movo1), encoding a member of the Ovo family of zinc-finger transcription
      factors, leads to germ cell degeneration and defective sperm production in adult
      mice. To explore the cellular and molecular mechanism of Ovol1 function, we have
      examined the mutant testis phenotype during the first wave of spermatogenesis in
      juvenile mice. Consistent with the detection of Ovol1 transcripts in pachytene
      spermatocytes of the meiotic prophase, Ovol1-deficient germ cells were defective
      in progressing through the pachytene stage. The pachytene arrest was accompanied
      by an inefficient exit from proliferation, increased apoptosis and an abnormal
      nuclear localization of the G2-M cell cycle regulator cyclin B1, but was not
      associated with apparent chromosomal or recombination defects. Transcriptional
      profiling and northern blot analysis revealed reduced expression of pachytene
      markers in the mutant, providing molecular evidence that pachytene
      differentiation was defective. In addition, the expression of Id2 (inhibitor of
      differentiation 2), a known regulator of spermatogenesis, was upregulated in
      Ovol1-deficient pachytene spermatocytes and repressed by Ovol1 in reporter
      assays. Taken together, our studies demonstrate a role for Ovol1 in regulating
      pachytene progression of male germ cells, and identify Id2 as a Ovol1 target.

PMID- 15716350
TI  - Plasticity of B cell receptor internalization upon conditional depletion of
      clathrin.
AB  - B cell antigen receptor (BCR) association with lipid rafts, the actin
      cytoskeleton, and clathrin-coated pits influences B cell signaling and antigen
      presentation. Although all three cellular structures have been separately
      implicated in BCR internalization, the relationship between them has not been
      clearly defined. In this study, internalization pathways were characterized by
      specifically blocking each potential mechanism of internalization. BCR uptake was
      reduced by approximately 70% in B cells conditionally deficient in clathrin heavy
      chain expression. Actin or raft antagonists were both able to block the residual,
      clathrin-independent BCR internalization. These agents also affected clathrin
      dependent internalization, indicating that clathrin-coated pits, in concert with
      mechanisms dependent on rafts and actin, mediate the majority of BCR
      internalization. Clustering G(M1) gangliosides enhanced clathrin-independent BCR
      internalization, and this required actin. Thus, although rafts or actin
      independently did not mediate BCR internalization, they apparently cooperate to
      promote some internalization even in the absence of clathrin. Simultaneous
      inhibition of all BCR uptake pathways resulted in sustained tyrosine
      phosphorylation and activation of the extracellular signal-regulated kinase
      (ERK), strongly suggesting that downstream BCR signaling can occur without
      receptor translocation to endosomes and that internalization leads to signal
      attenuation.

PMID- 15716351
TI  - Characterization of wild-type and deltaF508 cystic fibrosis transmembrane
      regulator in human respiratory epithelia.
AB  - Previous studies in native tissues have produced conflicting data on the
      localization and metabolic fate of WT and deltaF508 cystic fibrosis transmembrane
      regulator (CFTR) in the lung. Combining immunocytochemical and biochemical
      studies utilizing new high-affinity CFTR mAbs with ion transport assays, we
      examined both 1) the cell type and region specific expression of CFTR in normal
      airways and 2) the metabolic fate of deltaF508 CFTR and associated ERM proteins
      in the cystic fibrosis lung. Studies of lungs from a large number of normal
      subjects revealed that WT CFTR protein localized to the apical membrane of
      ciliated cells within the superficial epithelium and gland ducts. In contrast,
      other cell types in the superficial, gland acinar, and alveolar epithelia
      expressed little WT CFTR protein. No deltaF508 CFTR mature protein or function
      could be detected in airway specimens freshly excised from a large number of
      deltaF508 homozygous subjects, despite an intact ERM complex. In sum, our data
      demonstrate that WT CFTR is predominantly expressed in ciliated cells, and
      deltaF508 CFTR pathogenesis in native tissues, like heterologous cells, reflects
      loss of normal protein processing.

PMID- 15716352
TI  - EAPP, a novel E2F binding protein that modulates E2F-dependent transcription.
AB  - E2F transcription factors play an essential role in cell proliferation and
      apoptosis and their activity is frequently deregulated in human cancers. In a
      yeast two-hybrid screen we identified a novel E2F-binding protein. Due to its
      strong phosphorylation we named it EAPP (e2F-associated phosphoprotein). EAPP is
      localized in the nucleus and interacts with E2F-1, E2F-2, and E2F-3, but not with
      E2F-4. Examination of a number of human cell lines revealed that EAPP levels are
      elevated in most transformed cells. Moreover, EAPP mRNA was detected in all
      investigated human tissues in varying amounts. EAPP is present throughout the
      cell cycle but disappears during mitosis. In transfection assays with reporters
      controlled by either an artificial E2F-dependent promoter or the murine thymidine
      kinase promoter, EAPP increased the activation caused by E2F-1 but not by E2F-4.
      Surprisingly, the promoter of the p14(ARF) gene, which was also activated by E2F
      1, became repressed by EAPP. Overexpression of EAPP in U2OS cells resulted in a
      significant increase of cells in S-phase, whereas RNAi-mediated knock down of
      EAPP reduced the fraction of cells in S-phase. Taken together, these data suggest
      that EAPP modulates E2F-regulated transcription, stimulates proliferation, and
      may be involved in the malignant transformation of cells.

PMID- 15716353
TI  - Quantitative characterization of a mitotic cyclin threshold regulating exit from
      mitosis.
AB  - Regulation of cyclin abundance is central to eukaryotic cell cycle control.
      Strong overexpression of mitotic cyclins is known to lock the system in mitosis,
      but the quantitative behavior of the control system as this threshold is
      approached has only been characterized in the in vitro Xenopus extract system.
      Here, we quantitate the threshold for mitotic block in budding yeast caused by
      constitutive overexpression of the mitotic cyclin Clb2. Near this threshold, the
      system displays marked loss of robustness, in that loss or even heterozygosity
      for some regulators becomes deleterious or lethal, even though complete loss of
      these regulators is tolerated at normal cyclin expression levels. Recently, we
      presented a quantitative kinetic model of the budding yeast cell cycle. Here, we
      use this model to generate biochemical predictions for Clb2 levels, asynchronous
      as well as through the cell cycle, as the Clb2 overexpression threshold is
      approached. The model predictions compare well with biochemical data, even though
      no data of this type were available during model generation. The loss of
      robustness of the Clb2 overexpressing system is also predicted by the model.
      These results provide strong confirmation of the model's predictive ability.

PMID- 15716354
TI  - N-cadherin association with lipid rafts regulates its dynamic assembly at cell
      cell junctions in C2C12 myoblasts.
AB  - Cadherins are homophilic cell-cell adhesion molecules implicated in cell growth,
      differentiation, and organization into tissues during embryonic development. They
      accumulate at cell-cell contact sites and act as adhesion-activated signaling
      receptors. Here, we show that the dynamic assembly of N-cadherin at cell-cell
      contacts involves lipid rafts. In C2C12 myoblasts, immunofluorescence and
      biochemical experiments demonstrate that N-cadherin present at cell-cell contacts
      is colocalized with lipid rafts. Disruption of lipid rafts leads to the
      inhibition of cell-cell adhesion and disorganization of N-cadherin-dependent cell
      cell contacts without modifying the association of N-cadherin with catenins and
      its availability at the plasma membrane. Fluorescent recovery after
      photobleaching experiments demonstrate that at the dorsal plasma membrane, lipid
      rafts are not directly involved in the diffusional mobility of N-cadherin. In
      contrast, at cell-cell junctions N-cadherin association with lipid rafts allows
      its stabilization enabling the formation of a functional adhesive complex. We
      show that lipid rafts, as homophilic interaction and F-actin association,
      stabilize cadherin-dependent adhesive complexes. Homophilic interactions and F
      actin association of N-cadherin are both required for its association to lipid
      rafts. We thus identify lipid rafts as new regulators of cadherin-mediated cell
      adhesion.

PMID- 15716357
TI  - Partitions with short sequences and mock theta functions.
AB  - P. A. MacMahon was the first to examine integer partitions in which consecutive
      integers were not allowed as parts. Such partitions may be described as having
      sequences of length 1. Recently it was shown that partitions containing no
      sequences of consecutive integers of length k are of interest in seemingly
      unrelated problems concerning threshold growth models. The object now is to
      develop the subject intrinsically to both provide deeper understanding of the
      theory and application of partitions and reveal the surprising role of
      Ramanujan's mock theta functions.

PMID- 15716355
TI  - The type Ialpha inositol polyphosphate 4-phosphatase generates and terminates
      phosphoinositide 3-kinase signals on endosomes and the plasma membrane.
AB  - Endosomal trafficking is regulated by the recruitment of effector proteins to
      phosphatidylinositol 3-phosphate [PtdIns(3)P] on early endosomes. At the plasma
      membrane, phosphatidylinositol-(3,4)-bisphosphate [PtdIns(3,4)P2] binds the
      pleckstrin homology (PH) domain-containing proteins Akt and TAPP1. Type Ialpha
      inositol polyphosphate 4-phosphatase (4-phosphatase) dephosphorylates
      PtdIns(3,4)P2, forming PtdIns(3)P, but its subcellular localization is unknown.
      We report here in quiescent cells, the 4-phosphatase colocalized with early and
      recycling endosomes. On growth factor stimulation, 4-phosphatase endosomal
      localization persisted, but in addition the 4-phosphatase localized at the plasma
      membrane. Overexpression of the 4-phosphatase in serum-stimulated cells increased
      cellular PtdIns(3)P levels and prevented wortmannin-induced endosomal dilatation.
      Furthermore, mouse embryonic fibroblasts from homozygous Weeble mice, which have
      a mutation in the type I 4-phosphatase, exhibited dilated early endosomes. 4
      Phosphatase translocation to the plasma membrane upon growth factor stimulation
      inhibited the recruitment of the TAPP1 PH domain. The 4-phosphatase contains C2
      domains, which bound PtdIns(3,4)P2, and C2-domain-deletion mutants lost
      PtdIns(3,4)P2 4-phosphatase activity, did not localize to endosomes or inhibit
      TAPP1 PH domain membrane recruitment. The 4-phosphatase therefore both generates
      and terminates phosphoinositide 3-kinase signals at distinct subcellular
      locations.

PMID- 15716356
TI  - Involvement of the actin cytoskeleton and homotypic membrane fusion in ER
      dynamics in Caenorhabditis elegans.
AB  - The endoplasmic reticulum (ER) is the major intracellular membrane system. The ER
      is essential for protein and lipid biosynthesis, transport of proteins along the
      secretory pathway, and calcium storage. Here, we describe our investigations into
      the dynamics and regulation of the ER in the early Caenorhabditis elegans embryo.
      Using a GFP fusion to the ER-resident signal peptidase SP12, we observed the
      morphological transitions of the ER through fertilization and the early cell
      cycles in living embryos. These transitions were tightly coordinated with the
      division cycle: upon onset of mitosis, the ER formed structured sheets that
      redispersed at the initiation of cleavage. Although microtubules were not
      required for the transition of the ER between these different states, the actin
      cytoskeleton facilitated the dispersal of the ER at the end of mitosis. The ER
      had an asymmetric distribution in the early embryo, which was dependent on the
      establishment of polarity by the PAR proteins. The small GTPase ARF-1 played an
      essential role in the ER dynamics, although this function appeared to be
      unrelated to the role of ARF-1 in vesicular traffic. In addition, the ER-resident
      heat shock protein BiP and a homologue of the AAA ATPase Cdc48/p97 were found to
      be crucial for the ER transitions. Both proteins have been implicated in
      homotypic ER membrane fusion. We provide evidence that homotypic membrane fusion
      is required to form the sheet structure in the early embryo.

PMID- 15716358
TI  - Lessons from Escherichia coli genes similarly regulated in response to nitrogen
      and sulfur limitation.
AB  - We previously characterized nutrient-specific transcriptional changes in
      Escherichia coli upon limitation of nitrogen (N) or sulfur (S). These global
      homeostatic responses presumably minimize the slowing of growth under a
      particular condition. Here, we characterize responses to slow growth per se that
      are not nutrient-specific. The latter help to coordinate the slowing of growth,
      and in the case of down-regulated genes, to conserve scarce N or S for other
      purposes. Three effects were particularly striking. First, although many genes
      under control of the stationary phase sigma factor RpoS were induced and were
      apparently required under S-limiting conditions, one or more was inhibitory under
      N-limiting conditions, or RpoS itself was inhibitory. RpoS was, however,
      universally required during nutrient downshifts. Second, limitation for N and S
      greatly decreased expression of genes required for synthesis of flagella and
      chemotaxis, and the motility of E. coli was decreased. Finally, unlike the
      response of all other met genes, transcription of metE was decreased under S- and
      N-limiting conditions. The metE product, a methionine synthase, is one of the
      most abundant proteins in E. coli grown aerobically in minimal medium. Responses
      of metE to S and N limitation pointed to an interesting physiological rationale
      for the regulatory subcircuit controlled by the methionine activator MetR.

PMID- 15716359
TI  - Identification of combinatorial drug regimens for treatment of Huntington's
      disease using Drosophila.
AB  - We explore the hypothesis that pathology of Huntington's disease involves
      multiple cellular mechanisms whose contributions to disease are incrementally
      additive or synergistic. We provide evidence that the photoreceptor neuron
      degeneration seen in flies expressing mutant human huntingtin correlates with
      widespread degenerative events in the Drosophila CNS. We use a Drosophila
      Huntington's disease model to establish dose regimens and protocols to assess the
      effectiveness of drug combinations used at low threshold concentrations. These
      proof of principle studies identify at least two potential combinatorial
      treatment options and illustrate a rapid and cost-effective paradigm for testing
      and optimizing combinatorial drug therapies while reducing side effects for
      patients with neurodegenerative disease. The potential for using prescreening in
      Drosophila to inform combinatorial therapies that are most likely to be effective
      for testing in mammals is discussed.

PMID- 15716361
TI  - Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of
      the ubiquitin-proteasome system and alpha-synuclein.
AB  - In animals, sporadic injections of the mitochondrial toxin 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) selectively damage dopaminergic neurons but do
      not fully reproduce the features of human Parkinson's disease. We have now
      developed a mouse Parkinson's disease model that is based on continuous MPTP
      administration with an osmotic minipump and mimics many features of the human
      disease. Although both sporadic and continuous MPTP administration led to severe
      striatal dopamine depletion and nigral cell loss, we find that only continuous
      administration of MPTP produced progressive behavioral changes and triggered
      formation of nigral inclusions immunoreactive for ubiquitin and alpha-synuclein.
      Moreover, only continuous MPTP infusions caused long-lasting activation of
      glucose uptake and inhibition of the ubiquitin-proteasome system. In mice lacking
      alpha-synuclein, continuous MPTP delivery still induced metabolic activation, but
      induction of behavioral symptoms and neuronal cell death were almost completely
      alleviated. Furthermore, the inhibition of the ubiquitinproteasome system and the
      production of inclusion bodies were reduced. These data suggest that continuous
      low-level exposure of mice to MPTP causes a Parkinson-like syndrome in an alpha
      synuclein-dependent manner.

PMID- 15716360
TI  - Dopamine supersensitivity correlates with D2High states, implying many paths to
      psychosis.
AB  - Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after
      hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene
      knockouts of Dbh (dopamine beta-hydroxylase), Drd4 receptors, Gprk6 (G protein
      coupled receptor kinase 6), Comt (catechol-O-methyltransferase), or Th-/-,
      DbhTh/+ (tyrosine hydroxylase), and in rats born by Cesarean-section. The
      functional state of D2, or the high-affinity state for dopamine (D2High), was
      measured in these supersensitive animal brain striata. Increased levels and
      higher proportions (40-900%) for D2High were found in all these tissues. If many
      types of brain impairment cause dopamine behavioral supersensitivity and a common
      increase in D2High states, it suggests that there are many pathways to psychosis,
      any one of which can be disrupted.

PMID- 15716362
TI  - Label-free detection of small-molecule-protein interactions by using nanowire
      nanosensors.
AB  - Development of miniaturized devices that enable rapid and direct analysis of the
      specific binding of small molecules to proteins could be of substantial
      importance to the discovery of and screening for new drug molecules. Here, we
      report highly sensitive and label-free direct electrical detection of small
      molecule inhibitors of ATP binding to Abl by using silicon nanowire field-effect
      transistor devices. Abl, which is a protein tyrosine kinase whose constitutive
      activity is responsible for chronic myelogenous leukemia, was covalently linked
      to the surfaces of silicon nanowires within microfluidic channels to create
      active electrical devices. Concentration-dependent binding of ATP and
      concentration-dependent inhibition of ATP binding by the competitive small
      molecule antagonist STI-571 (Gleevec) were assessed by monitoring the nanowire
      conductance. In addition, concentration-dependent inhibition of ATP binding was
      examined for four additional small molecules, including reported and previously
      unreported inhibitors. These studies demonstrate that the silicon nanowire
      devices can readily and rapidly distinguish the affinities of distinct small
      molecule inhibitors and, thus, could serve as a technology platform for drug
      discovery.

PMID- 15716363
TI  - Functional characterization of five novel CYP2C8 variants, G171S, R186X, R186G,
      K247R, and K383N, found in a Japanese population.
AB  - Cytochrome P450 2C8 is one of the primary enzymes responsible for the metabolism
      of a wide range of drugs such as paclitaxel, cerivastatin, and amiodarone. We
      have sequenced the CYP2C8 gene from 201 Japanese subjects and found five novel
      nonsynonymous single nucleotide polymorphisms (SNPs): 511G>A (G171S), 556C>T
      (R186X; X represents the translational stop codon), 556C>G (R186G), 740A>G
      (K247R), and 1149G>T (K383N), with the allele frequency of 0.0025. The CYP2C8
      variants were heterologously expressed in COS-1 cells and functionally
      characterized in terms of expression level, paclitaxel 6alpha-hydroxylase
      activity, and intracellular localization. The prematurely terminated R186X
      variant was undetectable by Western blotting and inactive toward paclitaxel
      6alpha-hydroxylation. The G171S, K247R, and K383N variants exhibited properties
      similar to those of the wild-type CYP2C8. Paclitaxel 6alpha-hydroxylase activity
      of the R186G transfectant was only 10 to 20% that of wild-type CYP2C8.
      Furthermore, the R186G variant displayed a lower level of protein expression in
      comparison to the wild type, which was restored by the addition of a proteasome
      inhibitor (MG-132; Z-Leu-Leu-Leu-aldehyde). The reduced CO-difference spectral
      analysis using recombinant proteins from an insect cell/baculovirus system
      revealed that the R186G variant has a minor peak at 420 nm in addition to the
      characteristic Soret peak at 450 nm, suggesting the existence of improperly
      folded protein. These results indicate that the novel CYP2C8 SNPs, 556C>T (R186X)
      and 556C>G (R186G), could influence the metabolism of CYP2C8 substrates such as
      paclitaxel and cerivastatin.

PMID- 15716364
TI  - Hepatic uptake of the novel antifungal agent caspofungin.
AB  - Caspofungin (CANCIDAS, a registered trademark of Merck & Co., Inc.) is a novel
      echinocandin antifungal agent used in the treatment of esophageal and invasive
      candidiases, invasive aspergillosis, and neutropenia. Available data suggest that
      the liver is a key organ responsible for caspofungin elimination in rodents and
      humans. Caspofungin is primarily eliminated by metabolic transformation; however,
      the rate of metabolism is slow. Accordingly, it was hypothesized that drug uptake
      transporters expressed on the basolateral domain of hepatocytes could
      significantly influence the extent of caspofungin uptake and subsequent
      elimination. In this study, experiments ranging from perfused rat livers to
      heterologous expression of individual hepatic uptake transporters were utilized
      to identify the transporter(s) responsible for the observed liver-specific uptake
      of this compound. Data from perfused rat liver studies were consistent with the
      presence of carrier-mediated caspofungin hepatic uptake, although this process
      appeared to be slow. To identify a relevant hepatic uptake transporter, we
      developed novel Tet-on HeLa cells expressing OATP1B1 (OATP-C, SLC21A6) and
      OATP1B3 (OATP8, SLC21A8), whose target gene can be overexpressed by the addition
      of doxycycline. A modest but statistically significant uptake of caspofungin was
      observed in cells overexpressing OATP1B1, but not OATP1B3. Taken together, these
      findings suggest that OATP1B1-mediated hepatic uptake may contribute to the
      overall elimination of this drug from the body.

PMID- 15716365
TI  - Expression, localization, and functional characteristics of breast cancer
      resistance protein in Caco-2 cells.
AB  - The function of breast cancer resistance protein (BCRP) and its role in drug
      absorption, distribution, and elimination has recently been evaluated. The
      objective of the present study was to examine the expression, localization, and
      functional characteristics of BCRP in Caco-2 cells, a widely used human
      intestinal epithelial cell model for investigating intestinal drug absorption.
      The expression of BCRP in Caco-2 cells was measured by Western blotting using the
      antibody BXP-21. Localization of BCRP was determined by an immunofluorescence
      technique using both antibodies BXP-21 and BXP-34. The drug efflux function of
      BCRP was evaluated via the epithelial transport of methotrexate (MTX) and estrone
      3-sulfate (E3S) across Caco-2 cell monolayers in the presence or absence of the
      BCRP inhibitors Ko143 or GF120918 (N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2
      isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine
      carboxamide). Results from Western blot assay indicated that Caco-2 cells in the
      late passage (p56) expressed a higher level of BCRP as compared with the level in
      the early passages (p33). The total amount of BCRP protein did not change after
      the cells were confluent. Immunofluorescence studies revealed the positive
      staining of BCRP on the apical membrane of Caco-2 cells but not on the
      basolateral membrane after cell confluence. MTX and E3S showed a preferential
      basolateral-toapical (B-to-A) transport across Caco-2 cell monolayers. Both BCRP
      inhibitors Ko143 and GF120918 increased the apical-to-basolateral (A-to-B)
      transport but decreased the B-to-A transport of MTX and E3S. Caco-2 cells may
      therefore be used as an in vitro model to study the transport characteristics of
      BCRP.

PMID- 15716366
TI  - Increase of neuronal response variability at higher processing levels as revealed
      by simultaneous recordings.
AB  - A key problem for neuronal information processing is the variability of spike
      trains, something that is likely to constrain the encoding of sensory signals. We
      measured interspike-interval variability (coefficient of variation) as well as
      spike-count variability (Fano factor) in the metathoracic auditory system of
      locusts. We performed simultaneous intracellular recordings at the first three
      processing levels to establish identical physiological conditions. This allows us
      to assess whether variability is generated anew or is reduced during synaptic
      transmission and processing. Both the interspike-interval variability as well as
      the spike-count variability revealed similar trends and showed an increase from
      the periphery to higher processing levels. This result was confirmed by single
      cell recordings. A comparison of ascending interneurons coding for sound
      direction and those encoding sound patterns showed that the latter respond more
      reliably to repeated stimulus presentations. In general, the variability of
      spiking responses was much lower than expected from a Poisson process.
      Furthermore, we observed a strong dependence of variability on the spike rate,
      which differed at the three levels investigated. The differences in spike rates
      account for most of the differences in variability observed between processing
      levels. For auditory receptors, we found a good agreement between the Fano factor
      and the squared coefficient of variation, suggesting similarities to a renewal
      process of spike generation at the periphery. At the level of interneurons, the
      Fano factor was lower than the squared coefficient of variation; this indicates a
      higher reliability than expected from the interspike-interval distribution.

PMID- 15716367
TI  - Effects of aging on the regularity of physiological tremor.
AB  - The purpose of this investigation was to determine the effects of healthy aging
      on the regularity of physiological tremor under rest and postural conditions.
      Additionally, we examined the contribution of mechanical reflex factors to age
      related changes in postural physiological tremor. Tremor regularity, tremor
      electromyographic (EMG) coherence, tremor amplitude, and tremor modal frequency
      were calculated for 4 age groups (young: 20-30 yr, young-old: 60-69 yr, old: 70
      79 yr, and old-old: 80-94 yr) under resting and loaded postural conditions. There
      were 6 important findings from this study: 1) there were no differences between
      the young and elderly subjects for any of the dependent variables measured under
      the rest condition; 2) postural physiological tremor regularity was increased in
      the elderly; 3) postural physiological tremor-EMG coherence was also increased in
      the elderly, and there was a strong linear relation between peak tremor-EMG
      coherence in the 1- to 8-Hz frequency band and regularity of tremor. This
      relation was primarily driven by the increased magnitude of tremor-EMG coherence
      at 5.85 and 6.83 Hz; 4) enhanced mechanical reflex properties were not
      responsible for the increased magnitude of tremor-EMG coherence in the elderly
      subjects; 5) tremor amplitude was not different between the 4 age groups, but
      there was a slight decline in tremor modal frequency in the oldest age group in
      the unloaded condition; and 6) despite the increases in postural physiological
      tremor regularity and the magnitude of low frequency tremor-EMG coherence with
      age, there was a clear demarcation between healthy aging and previously published
      findings related to tremor pathology.

PMID- 15716368
TI  - Testing Bayesian models of human coincidence timing.
AB  - A sensorimotor control task often requires an accurate estimation of the timing
      of the arrival of an external target (e.g., when hitting a pitched ball).
      Conventional studies of human timing processes have ignored the stochastic
      features of target timing: e.g., the speed of the pitched ball is not generally
      constant, but is variable. Interestingly, based on Bayesian theory, it has been
      recently shown that the human sensorimotor system achieves the optimal estimation
      by integrating sensory information with prior knowledge of the probabilistic
      structure of the target variation. In this study, we tested whether Bayesian
      integration is also implemented while performing a coincidence-timing type of
      sensorimotor task by manipulating the trial-by-trial variability (i.e., the prior
      distribution) of the target timing. As a result, within several hundred trials of
      learning, subjects were able to generate systematic timing behavior according to
      the width of the prior distribution, as predicted by the optimal Bayesian model.
      Considering the previous studies showing that the human sensorimotor system uses
      Bayesian integration in spacing and force-grading tasks, our result indicates
      that Bayesian integration is fundamental to all aspects of human sensorimotor
      control. Moreover, it was noteworthy that the subjects could adjust their
      behavior both when the prior distribution was switched from wide to narrow and
      vice versa, although the adjustment was slower in the former case. Based on a
      comparison with observations in a previous study, we discuss the flexibility and
      adaptability of Bayesian sensorimotor learning.

PMID- 15716369
TI  - Background synaptic conductance and precision of EPSP-spike coupling at pyramidal
      cells.
AB  - The temporal precision of converting excitatory postsynaptic potentials (EPSPs)
      into spikes at pyramidal cells is critical for the coding of information in the
      cortex. Several in vitro studies have shown that voltage-dependent conductances
      in pyramidal cells can prolong the EPSP time course resulting in an imprecise
      EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo
      background synaptic conductance in cortical slices and investigated how the
      ongoing synaptic activity may affect the EPSP time course near threshold and the
      EPSP spike coupling. We report here that background synaptic conductance
      dramatically diminished the depolarization related prolongation of the EPSPs in
      pyramidal cells and improved the precision of spike timing. Furthermore, we found
      that background synaptic conductance can affect the interaction among action
      potentials in a spike train. Thus the level of ongoing synaptic activity in the
      cortex may regulate the capacity of pyramidal cells to process temporal
      information.

PMID- 15716370
TI  - 5-HT1B receptor-mediated presynaptic inhibition of GABA release in the
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that
      modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic receptors
      on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites
      in the SCN are located on nonretinal terminals and most axonal terminals in the
      SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B receptors might
      also be located on SCN GABAergic terminals by examining the effects of the highly
      selective 5-HT1B receptor agonist CP-93,129 on SCN miniature inhibitory
      postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were
      obtained from rat and mouse SCN neurons in hypothalamic slices. Using CsCl
      containing microelectrodes with QX314, we isolated mPSCs that were sensitive to
      the GABAA receptor antagonist, bicuculline. Bath application of CP-93,129 (1
      microM) decreased the frequency of mIPSCs by an average of 22% (n = 7) in rat SCN
      neurons and by an average of 30% (n = 8) in mouse SCN neurons with no clear
      effect on mIPSC amplitude. In mice lacking functional 5-HT1B receptors, CP-93,129
      (1 microM) had no clear effect on the frequency or the amplitude of mIPSCs
      recorded in any of the cells tested (n = 4). The decrease in the frequency of
      mIPSCs of SCN neurons produced by the selective 5-HT1B receptor agonist CP-93,129
      is consistent with the interpretation that 5-HT1B receptors are located on GABA
      terminals in the SCN and that 5-HT inhibits GABA release via a 5-HT1B presynaptic
      receptor-mediated mechanism.

PMID- 15716371
TI  - Distinguishable brain activation networks for short- and long-term motor skill
      learning.
AB  - The acquisition of a new motor skill is characterized first by a short-term, fast
      learning stage in which performance improves rapidly, and subsequently by a long
      term, slower learning stage in which additional performance gains are
      incremental. Previous functional imaging studies have suggested that distinct
      brain networks mediate these two stages of learning, but direct comparisons using
      the same task have not been performed. Here we used a task in which subjects
      learn to track a continuous 8-s sequence demanding variable isometric force
      development between the fingers and thumb of the dominant, right hand. Learning
      associated changes in brain activation were characterized using functional MRI
      (fMRI) during short-term learning of a novel sequence, during short-term learning
      after prior, brief exposure to the sequence, and over long-term (3 wk) training
      in the task. Short-term learning was associated with decreases in activity in the
      dorsolateral prefrontal, anterior cingulate, posterior parietal, primary motor,
      and cerebellar cortex, and with increased activation in the right cerebellar
      dentate nucleus, the left putamen, and left thalamus. Prefrontal, parietal, and
      cerebellar cortical changes were not apparent with short-term learning after
      prior exposure to the sequence. With long-term learning, increases in activity
      were found in the left primary somatosensory and motor cortex and in the right
      putamen. Our observations extend previous work suggesting that distinguishable
      networks are recruited during the different phases of motor learning. While short
      term motor skill learning seems associated primarily with activation in a
      cortical network specific for the learned movements, long-term learning involves
      increased activation of a bihemispheric cortical-subcortical network in a pattern
      suggesting "plastic" development of new representations for both motor output and
      somatosensory afferent information.

PMID- 15716372
TI  - Roles of gravitational cues and efference copy signals in the rotational updating
      of memory saccades.
AB  - Primates are able to localize a briefly flashed target despite intervening
      movements of the eyes, head, or body. This ability, often referred to as
      updating, requires extraretinal signals related to the intervening movement. With
      active roll rotations of the head from an upright position it has been shown that
      the updating mechanism is 3-dimensional, robust, and geometrically sophisticated.
      Here we examine whether such a rotational updating mechanism operates during
      passive motion both with and without inertial cues about head/body position in
      space. Subjects were rotated from either an upright or supine position, about a
      nasal-occipital axis, briefly shown a world-fixed target, rotated back to their
      original position, and then asked to saccade to the remembered target location.
      Using this paradigm, we tested subjects' abilities to update from various tilt
      angles (0, +/-30, +/-45, +/-90 degrees), to 8 target directions and 2 target
      eccentricities. In the upright condition, subjects accurately updated the
      remembered locations from all tilt angles independent of target direction or
      eccentricity. Slopes of directional errors versus tilt angle ranged from -0.011
      to 0.15, and were significantly different from a slope of 1 (no compensation for
      head-in-space roll) and a slope of 0.9 (no compensation for eye-in-space roll).
      Because the eyes, head, and body were fixed throughout these passive movements,
      subjects could not use efference copies or neck proprioceptive cues to assess the
      amount of tilt, suggesting that vestibular signals and/or body proprioceptive
      cues suffice for updating. In the supine condition, where gravitational signals
      could not contribute, slopes ranged from 0.60 to 0.82, indicating poor updating
      performance. Thus information specifying the body's orientation relative to
      gravity is critical for maintaining spatial constancy and for distinguishing body
      fixed versus world-fixed reference frames.

PMID- 15716373
TI  - Electrical stimulation of the anterior cingulate cortex reduces responses of rat
      dorsal horn neurons to mechanical stimuli.
AB  - The anterior cingulate cortex (ACC) is involved in the affective and motivational
      aspect of pain perception. Behavioral studies show a decreased avoidance behavior
      to noxious stimuli without change in mechanical threshold after stimulation of
      the ACC. However, as part of the neural circuitry of behavioral reflexes, there
      is no evidence showing that ACC stimulation alters dorsal horn neuronal
      responses. We hypothesize that ACC stimulation has two phases: a short-term phase
      in which stimulation elicits antinociception and a long-term phase that follows
      stimulation to change the affective response to noxious input. To begin testing
      this hypothesis, the purpose of this study was to examine the response of spinal
      cord dorsal horn neurons during stimulation of the ACC. Fifty-eight wide dynamic
      range spinal cord dorsal horn neurons from adult Sprague-Dawley rats were
      recorded in response to graded mechanical stimuli (brush, pressure, and pinch) at
      their respective receptive fields, while simultaneous stepwise electrical
      stimulations (300 Hz, 0.1 ms, at 10, 20, and 30 V) were applied in the ACC. The
      responses to brush at control, 10, 20, and 30 V, and recovery were 14.2 +/- 1.4,
      12.3 +/- 1.2, 10.9 +/- 1.2, 10.3 +/- 1.1, and 14.1 +/- 1.4 spikes/s,
      respectively. The responses to pressure at control, 10, 20, and 30 V, and
      recovery were 39.8 +/- 4.7, 25.6 +/- 3.0, 25.0 +/- 3.0, 21.6 +/- 2.4, and 34.2 +/
      3.7 spikes/s, respectively. The responses to pinch at control, 10, 20, and 30 V,
      and recovery were 40.7 +/- 3.8, 30.6 +/- 3.1, 27.8 +/- 2.8, 27.2 +/- 3.2, and
      37.4 +/- 3.9 spikes/s, respectively. We conclude that electrical stimulation of
      the ACC induces significant inhibition of the responses of spinal cord dorsal
      horn neurons to noxious mechanical stimuli. The stimulation-induced inhibition
      begins to recover as soon as the stimulation is terminated. These results suggest
      differential short-term and long-term modulatory effects of the ACC stimulation
      on nociceptive circuits.

PMID- 15716374
TI  - Cellular organization by self-organization: mechanisms and models for Min protein
      dynamics.
AB  - We use the oscillating Min proteins of Escherichia coli as a prototype system to
      illustrate the current state and potential of modeling protein dynamics in space
      and time. We demonstrate how a theoretical approach has led to striking new
      insights into the mechanisms of self-organization in bacterial cells and indicate
      how these ideas may be applicable to more complex structure formation in
      eukaryotic cells.

PMID- 15716375
TI  - Temporal separation of replication and recombination requires the intra-S
      checkpoint.
AB  - In response to DNA damage and replication pausing, eukaryotes activate checkpoint
      pathways that prevent genomic instability by coordinating cell cycle progression
      with DNA repair. The intra-S-phase checkpoint has been proposed to protect
      stalled replication forks from pathological rearrangements that could result from
      unscheduled recombination. On the other hand, recombination may be needed to cope
      with either stalled forks or double-strand breaks resulting from hydroxyurea
      treatment. We have exploited fission yeast to elucidate the relationship between
      replication fork stalling, loading of replication and recombination proteins onto
      DNA, and the intra-S checkpoint. Here, we show that a functional recombination
      machinery is not essential for recovery from replication fork arrest and instead
      can lead to nonfunctional fork structures. We find that Rad22-containing foci are
      rare in S-phase cells, but peak in G2 phase cells after a perturbed S phase.
      Importantly, we find that the intra-S checkpoint is necessary to avoid aberrant
      strand-exchange events during a hydroxyurea block.

PMID- 15716376
TI  - Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in
      cancer cells lacking functional pRB and p53.
AB  - E2F/DP complexes were originally identified as potent transcriptional activators
      required for cell proliferation. However, recent studies revised this notion by
      showing that inactivation of total E2F/DP activity by dominant-negative forms of
      E2F or DP does not prevent cellular proliferation, but rather abolishes tumor
      suppression pathways, such as cellular senescence. These observations suggest
      that blockage of total E2F/DP activity may increase the risk of cancer. Here, we
      provide evidence that depletion of DP by RNA interference, but not overexpression
      of dominant-negative form of E2F, efficiently reduces endogenous E2F/DP activity
      in human primary cells. Reduction of total E2F/DP activity results in a dramatic
      decrease in expression of many E2F target genes and causes a senescence-like cell
      cycle arrest. Importantly, similar results were observed in human cancer cells
      lacking functional p53 and pRB family proteins. These findings reveal that E2F/DP
      activity is indeed essential for cell proliferation and its reduction immediately
      provokes a senescence-like cell cycle arrest.

PMID- 15716377
TI  - Linking axonal degeneration to microtubule remodeling by Spastin-mediated
      microtubule severing.
AB  - Mutations in the AAA adenosine triphosphatase (ATPase) Spastin (SPG4) cause an
      autosomal dominant form of hereditary spastic paraplegia, which is a retrograde
      axonopathy primarily characterized pathologically by the degeneration of long
      spinal neurons in the corticospinal tracts and the dorsal columns. Using
      recombinant Spastin, we find that six mutant forms of Spastin, including three
      disease-associated forms, are severely impaired in ATPase activity. In contrast
      to a mutation designed to prevent adenosine triphosphate (ATP) binding, an ATP
      hydrolysis-deficient Spastin mutant predicted to remain kinetically trapped on
      target proteins decorates microtubules in transfected cells. Analysis of disease
      associated missense mutations shows that some more closely resemble the canonical
      hydrolysis mutant, whereas others resemble the ATP-binding mutant. Using real
      time imaging, we show that Spastin severs microtubules when added to
      permeabilized, cytosol-depleted cells stably expressing GFP-tubulin. Using
      purified components, we also show that Spastin interacts directly with
      microtubules and is sufficient for severing. These studies suggest that defects
      in microtubule severing are a cause of axonal degeneration in human disease.

PMID- 15716378
TI  - Botulinum neurotoxin C initiates two different programs for neurite degeneration
      and neuronal apoptosis.
AB  - Clostridial neurotoxins are bacterial endopeptidases that cleave the major SNARE
      proteins in peripheral motorneurons. Here, we show that disruption of synaptic
      architecture by botulinum neurotoxin C1 (BoNT/C) in central nervous system
      neurons activates distinct neurodegenerative programs in the axo-dendritic
      network and in the cell bodies. Neurites degenerate at an early stage by an
      active caspase-independent fragmentation characterized by segregation of energy
      competent mitochondria. Later, the cell body mitochondria release cytochrome c,
      which is followed by caspase activation, apoptotic nuclear condensation, loss of
      membrane potential, and, finally, cell swelling and lysis. Recognition and
      scavenging of dying processes by glia also precede the removal of apoptotic cell
      bodies, in line with a temporal and spatial segregation of different degenerative
      processes. Our results suggest that, in response to widespread synaptic damage,
      neurons first dismantle their connections and finally undergo apoptosis, when
      their spatial relationships are lost.

PMID- 15716379
TI  - Cell migration without a lamellipodium: translation of actin dynamics into cell
      movement mediated by tropomyosin.
AB  - The actin cytoskeleton is locally regulated for functional specializations for
      cell motility. Using quantitative fluorescent speckle microscopy (qFSM) of
      migrating epithelial cells, we previously defined two distinct F-actin networks
      based on their F-actin-binding proteins and distinct patterns of F-actin turnover
      and movement. The lamellipodium consists of a treadmilling F-actin array with
      rapid polymerization-dependent retrograde flow and contains high concentrations
      of Arp2/3 and ADF/cofilin, whereas the lamella exhibits spatially random punctae
      of F-actin assembly and disassembly with slow myosin-mediated retrograde flow and
      contains myosin II and tropomyosin (TM). In this paper, we microinjected skeletal
      muscle alphaTM into epithelial cells, and using qFSM, electron microscopy, and
      immunolocalization show that this inhibits functional lamellipodium formation.
      Cells with inhibited lamellipodia exhibit persistent leading edge protrusion and
      rapid cell migration. Inhibition of endogenous long TM isoforms alters protrusion
      persistence. Thus, cells can migrate with inhibited lamellipodia, and we suggest
      that TM is a major regulator of F-actin functional specialization in migrating
      cells.

PMID- 15716380
TI  - L1, a novel target of beta-catenin signaling, transforms cells and is expressed
      at the invasive front of colon cancers.
AB  - Aberrant beta-catenin-TCF target gene activation plays a key role in colorectal
      cancer, both in the initiation stage and during invasion and metastasis. We
      identified the neuronal cell adhesion molecule L1, as a target gene of beta
      catenin-TCF signaling in colorectal cancer cells. L1 expression was high in
      sparse cultures and coregulated with ADAM10, a metalloprotease involved in
      cleaving and shedding L1's extracellular domain. L1 expression conferred
      increased cell motility, growth in low serum, transformation and tumorigenesis,
      whereas its suppression in colon cancer cells decreased motility. L1 was
      exclusively localized in the invasive front of human colorectal tumors together
      with ADAM10. The transmembrane localization and shedding of L1 by
      metalloproteases could be useful for detection and as target for colon cancer
      therapy.

PMID- 15716382
TI  - Subcellular alterations of protein kinase C isozymes in the rat brain after
      organophosphate poisoning.
AB  - The protein kinase C (PKC) signaling pathway has been associated with modulation
      of N-metyl-D-aspartate receptor activity, motor behavior, learning, and memory,
      all of which are severely impaired in organophosphate (OP) intoxication.
      Nevertheless, the role of PKC in OP intoxication is largely unknown. The present
      study attempted to characterize alterations in the immunoreactivity levels of PKC
      isozymes expressed in different brain areas in the rat following exposure to the
      nerve agent sarin (1x LD(50)). Furthermore, possible neuroprotective effect of
      selective PKC regulating peptide after such insult was evaluated. The results
      indicated that a significant reduction in the immunoreactivity level of the
      conventional betaII-PKC and the atypical zeta-PKC was observed in frontal cortex
      up to 24 h postsarin and in the striatum up to 5 days postsarin exposure. This
      reduction was in contrast to the increase in the immuno-reactivity level of both
      isozymes seen in the hippocampus or thalamus. Treatment with the anticonvulsant
      midazolam (0.5 mg/kg) 10 min postsarin exposure markedly reduced zeta-PKC
      immunoreactivity level and betaII-PKC in the membrane fractions in the
      hippocampus. betaII-PKC peptide (380 ng/kg), known to inhibit PKC translocation
      and activation, attenuated sarin-induced neuropathology. These observations
      suggest a role for both conventional and atypical PKC isozymes in OP-induced
      neuropathy in the rat and further support their involvement in cell death.

PMID- 15716381
TI  - Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is
      mediated by beta1 integrins.
AB  - The anti-angiogenic effect of thrombospondin-1 has been shown to be mediated
      through binding of the type-1 repeat (TSR) domain to the CD36 transmembrane
      receptor. We now report that the TSR domain can inhibit VEGF-induced migration in
      human umbilical vein endothelial cells (HUVEC), cells that lack CD36. Moreover,
      we identified beta1 integrins as a critical receptor in TSR-mediated inhibition
      of migration in HUVEC. Using pharmacological inhibitors of downstream VEGF
      receptor effectors, we found that phosphoinositide 3-kinase (PI3k) was essential
      for TSR-mediated inhibition of HUVEC migration, but that neither PLCgamma nor Akt
      was necessary for this response. Furthermore, beta1 integrins were critical for
      TSR-mediated inhibition of microvascular endothelial cells, cells that express
      CD36. Together, our results indicate that beta1 integrins mediate the anti
      migratory effects of TSR through a PI3k-dependent mechanism.

PMID- 15716383
TI  - Stilbazulenyl nitrone, a second-generation azulenyl nitrone antioxidant, confers
      enduring neuroprotection in experimental focal cerebral ischemia in the rat:
      neurobehavior, histopathology, and pharmacokinetics.
AB  - Stilbazulenyl nitrone (STAZN) is a potent lipophilic second-generation azulenyl
      nitrone antioxidant, which is highly neuroprotective in rodent models of cerebral
      ischemia and trauma. This study was conducted to establish whether the
      neuroprotection induced by STAZN persists with chronic survival and to
      characterize STAZN's pharmacokinetics. Physiologically regulated rats received a
      2-h middle cerebral artery occlusion by intraluminal suture and were treated with
      either STAZN [four 0.6 mg/kg doses i.p. administered at 2 (i.e., onset of
      recirculation), 4, 24, and 48 h; n = 16] or dimethyl sulfoxide vehicle (n = 11).
      They received sequential neurobehavioral examinations followed by quantitative
      neuropathology at 30 days. STAZN improved neurological deficits compared with
      vehicle controls, beginning within <2 h of the first dose and persisting
      throughout a 30-day survival. Large cystic necrotic infarcts were common in
      vehicle-treated rats but infrequent in STAZN-treated rats, and noninfarcted
      forebrain tissue was increased on average by 15%. In normal rats administered 5
      mg/kg STAZN i.v. in Solutol HS 15/ethanol/saline vehicle, STAZN blood levels
      exhibited a biexponential decline, with an initial half-life of 28 min and a
      subsequent slow decay with half-life of approximately 7 h. STAZN tissue levels at
      2 to 3 h were, on average, 2.5% of blood levels in forebrain, 56% in myocardium,
      and 41% in kidney. STAZN was concentrated in liver with initial concentrations
      averaging 5.2-fold above blood levels and a subsequent linear decline of 40%
      between 24 and 72 h. These results establish that STAZN confers enduring ischemic
      neuroprotection, has a long circulating half-life, and penetrates well into brain
      and other organs-characteristics favoring its potential therapeutic utility.

PMID- 15716384
TI  - In vivo characterization of 6beta-naltrexol, an opioid ligand with less inverse
      agonist activity compared with naltrexone and naloxone in opioid-dependent mice.
AB  - The mu-opioid receptor displays basal signaling activity, which seems to be
      enhanced by exposure to opioid agonists. This study assesses the in vivo
      pharmacology of the putative "neutral" antagonist 6beta-naltrexol in comparison
      to other ligands with varying efficacy, such as naloxone, an inverse agonist in
      the opioid-dependent state. ICR mice were used to generate full antagonist dose
      response curves for naloxone, naltrexone, nalbuphine, and 6beta-naltrexol in
      blocking acute antinociceptive effects of morphine and precipitating opioid
      withdrawal in models of physical dependence. 6beta-Naltrexol was roughly
      equipotent to naloxone and between 4.5- and 10-fold less potent than naltrexone
      in blocking morphine-induced antinociception and locomotor activity, showing that
      6beta-naltrexol enters the central nervous system. In contrast to naloxone and
      naltrexone, 6beta-naltrexol precipitated only minimal withdrawal at high doses in
      an acute dependence model and was approximately 77- and 30-fold less potent than
      naltrexone and naloxone, respectively, in precipitating withdrawal in a chronic
      dependence model. 6beta-Naltrexol reduced the inverse agonist effects of naloxone
      in vitro and in vivo, as expected for a neutral antagonist. Therefore, the
      pharmacological effects of 6beta-naltrexol differ markedly from those of naloxone
      and naltrexone in the opioid-dependent state. A reduction of withdrawal effects
      associated with neutral mu-opioid receptor antagonists may offer advantages in
      treating opioid overdose and addiction.

PMID- 15716385
TI  - Site of action of beta-ligands at the human beta1-adrenoceptor.
AB  - Antagonist affinity measurements have traditionally been considered important in
      defining the receptor or receptor subtypes present within cells or tissues. Any
      change in this value has normally been taken as evidence for the presence of a
      second receptor. However, highly efficacious ligands induce a time and
      phosphorylation-dependent change in the beta2-adrenoceptor resulting in 10-fold
      lower affinity for antagonists. Also the beta1-adrenoceptor is now considered to
      exist in two different active conformations which are distinguished by their
      pharmacological properties. In this study, the site of action of a range of beta
      agonists and beta-antagonists was determined using the human beta1-adrenoceptor
      stably expressed in Chinese hamster ovary cells with cyclic AMP response element
      reporter genes. Adrenaline and noradrenaline were confirmed as having agonist
      actions via the catecholamine site, whereas all antagonists had higher affinity
      for the catecholamine rather than secondary site. However, the rank order of
      affinity for the two sites was different suggesting that they are indeed separate
      entities. The measurements of antagonist affinity at the catecholamine site,
      however, were found to depend upon the agonist present. For example, xamoterol,
      cimaterol, terbutaline, and formoterol agonist responses were more readily
      antagonized by CGP 20712A[2-hydroxy-5-(2-[{hydroxy-3-(4-[1-methyl-4
      trifluoromethyl-2-imidazolyl]phenoxy)propyl}amino]ethoxy)benzamide] than the
      catecholamine responses themselves. This, however, was not related to agonist
      efficacy as has previously been reported for the human beta2-adrenoceptor.
      Therefore, it may be that some agonists (e.g., cimaterol) purely activate the
      catecholamine site and others purely activate the secondary site (e.g., CGP 12177
      [(-)-4-(3-tert-butylamino-2-hydroxypropoxy)-benzimidazol-2-one]), whereas the
      others (e.g., catecholamines) activate both sites to differing degrees.

PMID- 15716386
TI  - Differential agonist-mediated internalization of the human 5-hydroxytryptamine 7
      receptor isoforms.
AB  - The human 5-hydroxytryptamine 7 (5-HT(7)) serotonin receptor is a class A G
      protein coupled receptor that has three isoforms, 5-HT(7(a)), 5-HT(7(b)), and 5
      HT(7(d)), which are produced by alternative splicing. The 5-HT(7) receptors are
      expressed in discrete areas of the brain and in both vascular and
      gastrointestinal smooth muscle. Central nervous system 5-HT(7) receptors may play
      a role in mood and sleep disorders. 5-HT(7) receptors show high affinity for a
      number of antidepressants and typical and atypical antipsychotics. We report here
      that the human 5-HT(7(d)) isoform expressed in human embryonic kidney (HEK) 293
      cells exhibits a pattern of receptor trafficking in response to agonist that
      differ from 5-HT(7(a)) or 5-HT(7(b)) isoforms. We employed a modification of a
      live cell-labeling technique to demonstrate that surface 5-HT(7(d)) receptors are
      constitutively internalized in the absence of agonist. This is in contrast to 5
      HT(7(a)) and 5-HT(7(b)) isoforms, which do not show this profound agonist
      independent internalization. Indeed, the 5-HT(7(d)) isoform displays this
      internalization in the presence of a 5-HT(7) -specific antagonist. In addition,
      the human 5-HT(7) isoform shows a diminished efficacy in stimulation of cAMP
      responsive reporter gene activity in transfected cells compared with 5-HT(7(a))
      or 5-HT(7(b)) receptors expressed at comparable levels. Thus, the carboxy
      terminal tail of 5-HT(7(d)), which is the longest among known human 5-HT(7)
      isoforms, may contain a motif that interacts with cellular transport mechanisms
      that is distinct from 5-HT(7(a)) and 5-HT(7(b)).

PMID- 15716387
TI  - Critical limb ischemia: hybrid MR angiography compared with DSA.
AB  - PURPOSE: To compare a hybrid magnetic resonance (MR) angiography protocol with
      selective digital subtraction angiography (DSA) in patients with critical limb
      ischemia. MATERIALS AND METHODS: The study was approved by the institutional
      review board, and written consent was obtained from all patients. Pretreatment
      DSA and hybrid MR angiography were performed in 19 consecutive patients (15 men,
      four women; mean age, 69.8 years; range, 44-86 years). Hybrid MR angiography
      included submillimeter dual-phase three-dimensional gadolinium-enhanced MR
      angiography in lower calf and foot, and four-station bolus-chase MR angiography
      in pelvis, thigh, and upper calf. Three readers identified the target lesion and
      inflow and outflow segments and determined treatment (bypass graft placement,
      percutaneous transluminal angioplasty, conservative management, amputation).
      Results of interobserver and intermethod comparisons were expressed as percentage
      of agreement and 95% confidence interval (CI). RESULTS: On hybrid MR angiograms,
      no substantial venous overlay was present and image quality was excellent or
      adequate in 18 (95%) of 19 limbs. Readers 1, 2, and 3 selected the identical
      target lesion on the DSA image and the MR angiogram in 18, 17, and 18 of 18
      comparable limbs, respectively. Mean percentage of agreement for readers 1 and 3
      was 100% (95% CI: 81%, 100%) and for reader 2 was 94% (95% CI: 73%, 100%).
      Agreement of all three readers was superior with use of MR angiography for
      determination of inflow segments (13 [72%] of 18 limbs) and outflow segments (17
      [94%] of 18 limbs), compared with agreement with use of DSA (13 [68%] of 19
      inflow segments, 10 [53%] of 19 outflow segments). Agreement in therapy decisions
      was higher with DSA (15 [79%] of 19) than with MR angiography (11 [61%] of 18).
      CONCLUSION: Preliminary data strongly support the combination of submillimeter
      dual-phase MR angiography in lower calf and foot with four-station bolus-chase MR
      angiography to extend the utility of MR angiography to patients with critical
      limb ischemia.

PMID- 15716388
TI  - Optimization of multi-detector row CT urography: effect of compression, saline
      administration, and prolongation of acquisition delay.
AB  - PURPOSE: To retrospectively compare the effects of abdominal compression,
      intravenous saline hydration, and two imaging delays on both distention and
      opacification of the intrarenal collecting system and ureter during multi
      detector row computed tomographic (CT) urography. MATERIALS AND METHODS:
      Institutional review board approval for reviewing images and medical records of
      the patients was obtained; informed patient consent was not required. Excretory
      phase images obtained from multi-detector row CT urography in 85 patients (57
      men, 28 women) were reviewed. Examinations were performed by using one of four
      techniques: abdominal compression and intravenous hydration with 250 mL of normal
      saline, compression only, intravenous hydration with saline only, and neither
      compression nor saline hydration. Excretory phase imaging was performed at 300
      and 450 seconds for each patient. Two reviewers measured urinary tract distention
      on transverse images and graded opacification and image quality on volume
      rendered images. Effects were compared by using statistical mixed models with
      repeated-measures analysis of variance. RESULTS: Saline hydration significantly
      improved opacification (P = .02) and overall image quality (P < .001) of the
      intrarenal collecting system and proximal ureter. Delayed excretory phase image
      acquisition of 450 seconds significantly increased distention of the intrarenal
      collecting system and proximal ureter (P < .001). No significant effects
      involving the lower segment of the ureter were seen with any technique; however,
      there were fewer nonvisualized distal ureteral segments with the longer imaging
      delay. CONCLUSION: Compression does not significantly improve distention or
      opacification of the urinary tract. Saline hydration is effective in improving
      opacification of the proximal urinary tract. Longer imaging delays improve
      distention of the proximal urinary tract and may aid in visualization of the
      lower segment of the ureter.

PMID- 15716389
TI  - MR arthrography of rotator interval, long head of the biceps brachii, and biceps
      pulley of the shoulder.
AB  - The rotator interval and the long head of the biceps brachii tendon are
      anatomically closely associated structures believed to confer stability to the
      shoulder joint. Abnormalities of the rotator interval may be acquired or
      congenital and are associated with instability of the long head of the biceps
      brachii tendon. Clinical and arthroscopic diagnoses of rotator interval
      abnormalities and subtle instability patterns of the long head of the biceps
      brachii tendon are difficult. Magnetic resonance arthrography, owing to its
      superior depiction of ligaments with distention of the joint capsule, may be the
      procedure of choice, barring open surgery, for help in diagnosis of these
      conditions.

PMID- 15716390
TI  - Amplitude-modulated continuous arterial spin-labeling 3.0-T perfusion MR imaging
      with a single coil: feasibility study.
AB  - Written informed consent was obtained prior to all human studies after the
      institutional review board approved the protocol. A continuous arterial spin
      labeling technique with an amplitude-modulated control was implemented by using a
      single coil at 3.0 T. Adiabatic inversion efficiency at 3.0 T, comparable to that
      at 1.5 T, was achieved by reducing the amplitude of radiofrequency pulses and
      gradient strengths appropriately. The amplitude-modulated control provided a good
      match for the magnetization transfer effect of labeling pulses, allowing
      multisection perfusion magnetic resonance imaging of the whole brain. Comparison
      of multisection continuous and pulsed arterial spin-labeling methods at 3.0 T
      showed a 33% improvement in signal-to-noise ratio by using the former approach.

PMID- 15716391
TI  - Accommodation of requests for emergency US and CT: applications of queueing
      theory to scheduling of urgent studies.
AB  - The purpose of this study was to determine whether queueing theory would allow
      prediction of optimal number of schedule slots to be reserved for urgent computed
      tomography (CT) and ultrasonography (US). Institutional review board approval was
      obtained; informed consent was exempted. Emergency studies were modeled as a
      Poisson process; slots were reserved such that rate of rescheduling of routine
      studies to accommodate emergencies was predicted to be below a certain level.
      Model was tested with 3 years of emergency US and CT requests. US and CT requests
      showed Poisson distribution. US rescheduling was near that predicted. CT
      rescheduling exceeded that predicted, which reflected increasing CT use. By using
      more recent CT data for prediction, a more concordant rescheduling rate resulted.

PMID- 15716392
TI  - Peripheral solitary pulmonary nodule: CT findings in patients with pulmonary
      emphysema.
AB  - PURPOSE: To analyze retrospectively the computed tomographic (CT) features of
      peripheral noncalcified solitary pulmonary nodules in patients with and those
      without emphysema. MATERIALS AND METHODS: The authors' institutional review board
      required neither its approval nor patient informed consent for this retrospective
      study. The authors retrospectively reviewed 2-mm-thick CT images of 41 nodules
      (21 malignant, 20 benign) in 41 patients with emphysema (age range, 58-88 years;
      mean, 71.9 years) and 40 nodules (20 malignant, 20 benign) in 40 patients without
      emphysema (age range, 50-85 years; mean, 69.2 years). Two radiologists who were
      unaware of the diagnosis independently evaluated the shape and margin of the
      nodule, recorded the presence of ground-glass opacities and air bronchograms, and
      classified nodules into two diagnostic categories: malignant and benign. Final
      decisions were reached by consensus. For quantitative assessment of the nodules,
      the fractal dimensions of the nodule interfaces and circularity of the nodule
      shape were calculated with an image-processing program, and the percentage of the
      nodule surrounded by emphysema was obtained. Statistical comparisons were made
      with a chi(2) or Fisher exact test and the Mann-Whitney U test. RESULTS: In
      patients with emphysema, there were no significant differences in fractal
      dimension, circularity, or frequency of lobulation or spiculation between
      malignant and benign nodules. Of the 41 nodules in patients with emphysema, 26
      (63%) were correctly diagnosed. Thirteen benign nodules (65%) were diagnosed as
      malignant in patients with emphysema. Of the 40 nodules in nonemphysematous
      lungs, 37 (93%) were correctly diagnosed. The mean percentage of emphysema around
      the nodule was greater for misdiagnosed nodules than for correctly diagnosed
      nodules (P = .003). CONCLUSION: Malignant and benign nodules associated with
      emphysema exhibited considerably more overlap in CT features than did nodules in
      nonemphysematous lungs.

PMID- 15716393
TI  - Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain
      specific adaptive responses to endurance or resistance training-like electrical
      muscle stimulation.
AB  - Endurance training induces a partial fast-to-slow muscle phenotype transformation
      and mitochondrial biogenesis but no growth. In contrast, resistance training
      mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of
      this study was to identify signaling events that may mediate the specific
      adaptations to these types of exercise. Isolated rat muscles were electrically
      stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100
      Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic
      endurance training). HFS significantly increased myofibrillar and sarcoplasmic
      protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had
      no significant effect on protein synthesis 3 h after stimulation but increased
      UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS
      increased AMPK phosphorylation significantly at Thr172 by approximately 2-fold
      and increased PGC-1alpha protein to 1.3 times of control. LFS had no effect on
      PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated
      translational regulators. In contrast, HFS acutely increased phosphorylation of
      PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3beta at PKB
      sensitive sites. HFS also caused a prolonged activation of the translational
      regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific
      signaling response to LFS is a specific activation of the AMPK-PGC-1alpha
      signaling pathway which may explain some endurance training adaptations. HFS
      selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of
      translational regulators, which is consistent with increased protein synthesis
      and muscle growth. We term this behavior the "AMPK-PKB switch." We hypothesize
      that the AMPK-PKB switch is a mechanism that partially mediates specific
      adaptations to endurance and resistance training, respectively.

PMID- 15716394
TI  - Gene expression in rat leydig cells during development from the progenitor to
      adult stage: a cluster analysis.
AB  - The postnatal development of Leydig cells can be divided into three distinct
      stages: initially they exist as fibroblast-like progenitor Leydig cells (PLCs)
      appearing in the testis by Days 14-21; subsequently, by Day 35, they become
      immature Leydig cells (ILCs) acquiring steroidogenic organelle structure and
      enzyme activities but metabolizing most of the testosterone they produce;
      finally, as adult Leydig cells (ALCs) by Day 90, they actively produce
      testosterone. The factors controlling proliferation and differentiation of Leydig
      cells remain largely unknown, and the aim of the present study was to identify
      changes in gene expression during development through cDNA array analysis of
      PLCs, ILCs, and ALCs. By cluster analysis, it was determined that the transitions
      from PLC to ILC to ALC were associated with downregulation of mRNAs corresponding
      to 107 genes. The downregulated genes included cell-cycle regulators, e.g.,
      cyclin D1 (Ccnd1); growth factors, e.g., basic fibroblast growth factor (Fgf2);
      growth-factor-related receptors, e.g., platelet-derived growth factor alpha
      receptor (Pdgfra); oncogenes, e.g., kit oncogene (Kit); and transcription
      factors, e.g., early growth response 1 (Egr1). Conversely, expression levels of
      264 genes were increased by at least twofold. Most of these were related to
      differentiated function and included steroidogenic enzymes, e.g., 11beta
      hydroxysteroid dehydrogenase 2 (Hsd11b2); neurotransmitter receptors, e.g.,
      acetylcholine receptor nicotinic alpha 4 (Chrna4); stress response factors, e.g.,
      glutathione transferase 8 (Gsta4); and protein turnover enzymes, e.g., tissue
      inhibitor of metalloproteinase 2 (Timp2). The detection of Hsd11b2 mRNA in the
      array was the first indication that this gene is expressed in Leydig cells, and
      parallel increases in Hsd11b2 mRNA and enzyme activity were recorded. Thus, gene
      profiling demonstrates that postnatal development is associated with changes in
      the expression levels of several different clusters of genes consistent with the
      processes of Leydig cell growth and differentiation.

PMID- 15716395
TI  - Microinjection of cytoplasm or mitochondria derived from somatic cells affects
      parthenogenetic development of murine oocytes.
AB  - Cloned mammals are readily obtained by nuclear transfer using cultured somatic
      cells; however, the rate of generating live offspring from the reconstructed
      embryos remains low. In nuclear transfer procedures, varying quantities of donor
      cell mitochondria are transferred with nuclei into recipient oocytes, and
      mitochondrial heteroplasmy has been observed. A mouse model was used to examine
      whether transferred mitochondria affect the development of the reconstructed
      oocytes. Cytoplasm or purified mitochondria from somatic cells derived from the
      external ear, skeletal muscle, and testis of Mus spretus mice or cumulus cells of
      Mus musculus domesticus mice were transferred into M. m. domesticus (B6SJLF1 and
      B6D2F1) oocytes to observe parthenogenetic development through the morula stage.
      All B6D2F1 oocytes injected with somatic cytoplasm or mitochondria showed delayed
      development when compared to oocytes injected with buffer. The developmental
      rates were not different among injected cell sources, with the exception of
      testis-derived donor cells injected into B6SJLF1 oocytes (P < 0.01). The
      developmental rate of B6D2F1 oocytes injected with buffer alone (98.8% survival)
      was different from those injected with somatic cytoplasm (60.8% survival) or
      somatic mitochondria (56.5% survival) (P < 0.01). Conversely, injection of
      ooplasm into B6D2F1 oocytes did not affect parthenogenetic development (100%
      survival). Our results indicate that injection of somatic cytoplasm or
      mitochondria affected parthenogenetic development of murine oocytes. These
      results have further implications for in vitro fertilization protocols employing
      ooplasmic transfer where primary oocyte failure is not confirmed.

PMID- 15716396
TI  - Animal-to-animal variability in motor pattern production in adults and during
      growth.
AB  - Which features of network output are well preserved during growth of the nervous
      system and across different preparations of the same size? To address this issue,
      we characterized the pyloric rhythms generated by the stomatogastric nervous
      systems of 99 adult and 12 juvenile lobsters (Homarus americanus). Anatomical
      studies of single pyloric network neurons and of the whole stomatogastric
      ganglion (STG) showed that the STG and its neurons grow considerably from
      juvenile to adult. Despite these changes in size, intracellularly recorded
      membrane potential waveforms of pyloric network neurons and the phase
      relationships in the pyloric rhythm were very similar between juvenile and adult
      preparations. Across adult preparations, the cycle period and number of spikes
      per burst were not tightly maintained, but the mean phase relationships were
      independent of the period of the rhythm and relatively tightly maintained across
      preparations. We interpret this as evidence for homeostatic regulation of network
      activity.

PMID- 15716397
TI  - Overexpression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a
      antibody-mediated injury in a model of acute motor axonal neuropathy.
AB  - Anti-GD1a ganglioside antibodies (Abs) are the serological hallmark of the acute
      motor axonal form of the post-infectious paralysis, Guillain-Barre syndrome.
      Development of a disease model in mice has been impeded by the weak
      immunogenicity of gangliosides and the apparent resistance of GD1a-containing
      neural membranes to anti-GD1a antibody-mediated injury. Here we used mice with
      altered ganglioside biosynthesis to generate such a model at motor nerve
      terminals. First, we bypassed immunological tolerance by immunizing GD1a
      deficient, beta-1,4-N-acetylgalactosaminyl transferase knock-out mice with GD1a
      ganglioside-mimicking antigens from Campylobacter jejuni and generated high-titer
      anti-GD1a antisera and complement fixing monoclonal Abs (mAbs). Next, we exposed
      ex vivo nerve-muscle preparations from GD1a-overexpressing, GD3 synthase knock
      out mice to the anti-GD1a mAbs in the presence of a source of complement and
      investigated morphological and electrophysiological damage. Dense antibody and
      complement deposits were observed only over presynaptic motor axons, accompanied
      by severe ultrastructural damage and electrophysiological blockade of motor nerve
      terminal function. Perisynaptic Schwann cells and postsynaptic membranes were
      unaffected. In contrast, normal mice were not only unresponsive to immunization
      with GD1a but also resistant to neural injury during anti-GD1a Ab exposure,
      demonstrating the central role of membrane antigen density in modulating both
      immune tolerance to GD1a and axonal susceptibility to anti-GD1a Abmediated
      injury. Identical paralyzing effects were observed when testing mouse and human
      anti-GD1a-positive sera. These data indicate that anti-GD1a Abs arise via
      molecular mimicry and are likely to be clinically relevant in injuring peripheral
      nerve axonal membranes containing sufficiently high levels of GD1a.

PMID- 15716398
TI  - Neurotensin activates GABAergic interneurons in the prefrontal cortex.
AB  - Converging data suggest a dysfunction of prefrontal cortical GABAergic
      interneurons in schizophrenia. Morphological and physiological studies indicate
      that cortical GABA cells are modulated by a variety of afferents. The peptide
      transmitter neurotensin may be one such modulator of interneurons. In the rat
      prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons
      and has been suggested to be decreased in schizophrenia. However, the effects of
      neurotensin on cortical interneurons are poorly understood. We used in vivo
      microdialysis in freely moving rats to assess whether neurotensin regulates PFC
      GABAergic interneurons. Intra-PFC administration of neurotensin concentration
      dependently increased extracellular GABA levels; this effect was impulse
      dependent, being blocked by treatment with tetrodotoxin. The ability of
      neurotensin to increase GABA levels in the PFC was also blocked by pretreatment
      with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3
      yl)carbonylamino]tricyclo(3.3.1.1 [EC] .3.7)decan-2-carboxylic acid (SR48692), a
      high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is
      consistent with our observation that NTR1 was localized to GABAergic interneurons
      in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin
      is exclusively localized to dopamine axons in the PFC, we also determined whether
      neurotensin plays a role in the ability of dopamine agonists to increase
      extracellular GABA levels. We found that D2 agonist-elicited increases in PFC
      GABA levels were blocked by pretreatment with SR48692, consistent with data
      indicating that D2 autoreceptor agonists increase neurotensin release from
      dopamine-neurotensin axons in the PFC. These findings suggest that neurotensin
      plays an important role in regulating prefrontal cortical interneurons and that
      it may be useful to consider neurotensin agonists as an adjunct in the treatment
      of schizophrenia.

PMID- 15716399
TI  - Language-related activations in the left prefrontal regions are differentially
      modulated by age, proficiency, and task demands.
AB  - It remains to be elucidated how cortical activations are modulated by factors of
      age, proficiency, and language task demands when mastering first language (L1)
      and a second language (L2). Using functional magnetic resonance imaging, we
      tested subjects aged 13 (the age 13 group) and 19 (the age 19 group), thereby
      comparing the cortical activations involved in past-tense verb identification
      with those involved in verb matching. We found that the activation in the dorsal
      triangular part of the left inferior frontal gyrus (IFG) was lower, corresponding
      to a higher proficiency in English (L2) in the older subjects, suggesting that
      the proficiency level plays a major role in the activation of this region during
      L2 acquisition. Moreover, the lower activation in the triangular and orbital
      parts of the left IFG (F3t/F3O) for the irregular past tense corresponding to a
      higher proficiency in L2, together with the nonsignificant activation for the
      regular past tense when its performance almost reached perfection for age 19,
      suggests that the modulation of the left F3t/F3O activation reflects language
      task demands for identifying correct past-tense forms. On the other hand, the
      left F3t/F3O activation in Japanese (L1) for age 13 was significantly greater
      than that for age 19, despite the matched performances in L1. These results
      suggest that the left IFG subserves language-specific functions that are
      critically required when mastering any language.

PMID- 15716400
TI  - Conditioning injury-induced spinal axon regeneration requires signal transducer
      and activator of transcription 3 activation.
AB  - Sensory axons in the adult spinal cord do not regenerate after injury. This is
      essentially because of inhibitory components in the damaged CNS, such as myelin
      associated inhibitors and the glial scar. However, if the sciatic nerve is
      axotomized before injury of the dorsal column, injured axons can regenerate a
      short distance in the spinal cord. Here, we show that sciatic nerve transection
      results in time-dependent phosphorylation and activation of the transcription
      factor, signal transducer and activator of transcription 3 (STAT3), in dorsal
      root ganglion (DRG) neurons. This effect is specific to peripheral injuries and
      does not occur when the dorsal column is crushed. Sustained perineural infusion
      of the Janus kinase 2 (JAK2) inhibitor AG490 to the proximal nerve stump can
      block STAT3 phosphorylation after sciatic nerve transection and results in
      reduced growth-associated protein 43 upregulation and compromised neurite
      outgrowth in vitro. Importantly, in vivo perineural infusion of AG490 also
      significantly attenuates dorsal column axonal regeneration in the adult spinal
      cord after a preconditioning sciatic nerve transection. We conclude that STAT3
      activation is necessary for increased growth ability of DRG neurons and improved
      axonal regeneration in the spinal cord after a conditioning injury.

PMID- 15716401
TI  - A novel pathway for presynaptic mitogen-activated kinase activation via AMPA
      receptors.
AB  - AMPA-type glutamate receptors play a key role in mediating postsynaptic responses
      of excitatory neurotransmitters. It is now well accepted that AMPA receptors are
      also present at the presynapse, where they are thought to modulate
      neurotransmitter release. However, the mechanisms through which they control
      synaptic vesicle traffic have remained elusive. We used cultured hippocampal
      neurons and growth cone particles prepared from fetal rat brain to investigate
      the functional role of presynaptic AMPA receptors. We show here that stimulation
      of presynaptic AMPA receptors induces activation of mitogen-activated protein
      kinase (MAPK) through a nonreceptor tyrosine kinase-dependent and Na+/Ca2+
      independent mechanism. This pathway is activated predominantly in axonal growth
      cones compared with the somatodendritic compartment. After stimulation of
      presynaptic AMPA receptors, synapsin I is phosphorylated at MAPK-specific sites.
      These events are paralleled by a prominent increase in evoked synaptic vesicle
      recycling that is blocked by the specific MAPK inhibitor 2-(2-amino-3
      methoxyphenyl)-4H-1-benzopyran-4-one. Similarly, in synaptosomes isolated from
      adult brain, AMPA stimulation induces MAPK activation and phosphorylation of
      synapsin I at MAPK-dependent sites and enhances significantly synaptic vesicle
      recycling. These results reveal a novel pathway for activation of presynaptic
      MAPK and suggest a role of this pathway in the regulation of short-term
      presynaptic plasticity.

PMID- 15716402
TI  - Excitatory effects of thyrotropin-releasing hormone in the thalamus.
AB  - The activity of the thalamus is state dependent. During slow-wave sleep, rhythmic
      burst firing is prominent, whereas during waking or rapid eye movement sleep,
      tonic, single-spike activity dominates. These state-dependent changes result from
      the actions of modulatory neurotransmitters. In the present study, we
      investigated the functional and cellular effects of the neuropeptide thyrotropin
      releasing hormone (TRH) on the spontaneously active ferret geniculate slice. This
      peptide and its receptors are prominently expressed in the thalamic network, yet
      the role of thalamic TRH remains obscure. Bath application of TRH resulted in a
      transient cessation of both spindle waves and the epileptiform slow oscillation
      induced by application of bicuculline. With intracellular recordings, TRH
      application to the GABAergic neurons of the perigeniculate (PGN) or
      thalamocortical cells in the lateral geniculate nucleus resulted in
      depolarization and increased membrane resistance. In perigeniculate neurons, this
      effect reversed near the reversal potential for K+, suggesting that it is
      mediated by a decrease in K+ conductance. In thalamocortical cells, the TRH
      induced depolarization was of sufficient amplitude to block the generation of
      rebound Ca2+ spikes, whereas the even larger direct depolarization of PGN neurons
      transformed these cells from the burst to tonic, single-spike mode of action
      potential generation. Furthermore, application of TRH prominently enhanced the
      afterdepolarization that follows rebound Ca2+ spikes, suggesting that this
      transmitter may also enhance Ca2+-activated nonspecific currents. These data
      suggest a novel role for TRH in the brain as an intrinsic regulator of
      thalamocortical network activity and provide a potential mechanism for the wake
      promoting and anti-epileptic effects of this peptide.

PMID- 15716403
TI  - Functional control of cold- and menthol-sensitive TRPM8 ion channels by
      phosphatidylinositol 4,5-bisphosphate.
AB  - Cold is detected by a small subpopulation of peripheral thermoreceptors. TRPM8, a
      cloned menthol- and cold-sensitive ion channel, has been suggested to mediate
      cold transduction in the innocuous range. The channel shows a robust response in
      whole-cell recordings but exhibits markedly reduced activity in excised membrane
      patches. Here we report that phosphatidylinositol 4,5-bisphosphate (PIP2) is an
      essential regulator of the channel function. The rundown of the channel is
      prevented by lipid phosphatase inhibitors. Application of exogenous PIP2 both
      activates the channel directly and restores rundown activity. Whole-cell
      experiments involving intracellular dialysis with polyvalent cations, inhibition
      of PIP2 synthesis kinases, and receptor-mediated hydrolysis of PIP2 show that
      PIP2 also modulates the channel activity in the intact cells. The crucial role of
      PIP2 on the function of TRPM8 suggests that the membrane PIP2 level may be an
      important regulator of cold transduction in vivo. The opposite effects of PIP2 on
      the vanilloid receptor TRPV1 and TRPM8 also implies that the membrane lipid may
      have dual actions as a bimodal switch to selectively control the heat- and cold
      induced responses in nociceptors expressing both channels.

PMID- 15716404
TI  - Activation of nuclear factor-kappaB via endogenous tumor necrosis factor alpha
      regulates survival of axotomized adult sensory neurons.
AB  - Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and
      cultured embryonic DRG neurons require exogenous neurotrophic factors that
      activate the neuroprotective transcription factor nuclear factor-kappaB (NF
      kappaB) for survival. In contrast, adult DRG neurons survive permanent axotomy in
      vivo and in defined culture media devoid of exogenous neurotrophic factors in
      vitro. Peripheral axotomy in adult rats induces local accumulation of the
      cytokine tumor necrosis factor alpha (TNFalpha), a potent activator of NF-kappaB
      activity. We tested the hypothesis that activation of NF-kappaB stimulated by
      endogenous TNFalpha was required for survival of axotomized adult sensory
      neurons. Peripheral axotomy of lumbar DRG neurons by sciatic nerve crush induced
      a very rapid (within 2 h) and significant elevation in NF-kappaB-binding
      activity. This phenomenon was mimicked in cultured neurons in which there was
      substantial NF-kappaB nuclear translocation and a significant rise in NF-kappaB
      DNA-binding activity after plating. Inhibitors of NF-kappaB (SN50 or NF-kappaB
      decoy DNA) resulted in necrotic cell death of medium to large neurons (> or =40
      microm) within 24 h (60 and 75%, respectively), whereas inhibition of p38 and
      mitogen-activated protein/extracellular signal-regulated kinase did not effect
      survival. ELISA revealed that these cultures contained TNFalpha, and exposure to
      an anti-TNFalpha antibody inhibited NF-kappaB DNA-binding activity by
      approximately 35% and killed approximately 40% of medium to large neurons within
      24 h. The results show for the first time that cytokine-mediated activation of NF
      kappaB is a component of the signaling pathway responsible for maintenance of
      adult sensory neuron survival after axon damage.

PMID- 15716405
TI  - Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic
      immunization efficacy in an animal model of Parkinson's disease.
AB  - Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease
      (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      intoxication. MPTP-treated animals show the common behavioral, motor, and
      pathological features of human disease. We demonstrated previously that adoptive
      transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal
      dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this
      protection by quantitative proton magnetic resonance spectroscopic imaging (1H
      MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl
      aspartate (NAA) was significantly diminished in the substantia nigra pars
      compacta (SNpc) and striatum, regions most affected in human disease. When the
      same regions were coregistered with immunohistochemical stains for tyrosine
      hydroxylase, numbers of neuronal bodies and termini were similarly diminished.
      MPTP-intoxicated animals that received Cop-1 immune cells showed NAA levels, in
      the SNpc and striatum, nearly equivalent to PBS-treated animals. Moreover,
      adoptive transfer of immune cells from ovalbumin-immunized to MPTP-treated mice
      failed to alter NAA levels or protect dopaminergic neurons and their projections.
      These results demonstrate that 1H MRSI can evaluate dopaminergic degeneration and
      its protection by Cop-1 immunization strategies. Most importantly, the results
      provide a monitoring system to assess therapeutic outcomes for PD.

PMID- 15716406
TI  - Ectopic norrin induces growth of ocular capillaries and restores normal retinal
      angiogenesis in Norrie disease mutant mice.
AB  - Norrie disease is an X-linked retinal dysplasia that presents with congenital
      blindness, sensorineural deafness, and mental retardation. Norrin, the protein
      product of the Norrie disease gene (NDP), is a secreted protein of unknown
      biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in
      norrin develop blindness, show a distinct failure in retinal angiogenesis, and
      completely lack the deep capillary layers of the retina. We show here that the
      transgenic expression of ectopic norrin under control of a lens-specific promoter
      restores the formation of a normal retinal vascular network in Ndp(y/-) mutant
      mice. The improvement in structure correlates with restoration of neuronal
      function in the retina. In addition, lenses of transgenic mice with ectopic
      expression of norrin show significantly more capillaries in the hyaloid
      vasculature that surrounds the lens during development. In vitro, lenses of
      transgenic mice in coculture with microvascular endothelial cells induce
      proliferation of the cells. Transgenic mice with ectopic expression of norrin
      show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day
      14.5 and thicker retinas at postnatal life than wild-type littermates, indicating
      a putative direct neurotrophic effect of norrin. These data provide direct
      evidence that norrin induces growth of ocular capillaries and that pharmacologic
      modulation of norrin might be used for treatment of the vascular abnormalities
      associated with Norrie disease or other vascular disorders of the retina.

PMID- 15716407
TI  - Chemokine signaling guides axons within the retina in zebrafish.
AB  - Chemokines are a large family of secreted proteins that play an important role in
      the migration of leukocytes during hematopoiesis and inflammation. Chemokines and
      their receptors are also widely distributed in the CNS. Although recent
      investigations are beginning to elucidate chemokine function within the CNS,
      relatively little is known about the CNS function of this important class of
      molecules. To better appreciate the CNS function of chemokines, the role of
      signaling by stromal cell-derived factor-1 (SDF-1) through its receptor,
      chemokine (CXC motif) receptor 4 (CXCR4), was analyzed in zebrafish embryos. The
      SDF-1/CXCR4 expression pattern suggested that SDF-1/CXCR4 signaling was important
      for guiding retinal ganglion cell axons within the retina to the optic stalk to
      exit the retina. Antisense knockdown of the ligand and/or receptor and a genetic
      CXCR4 mutation both induced retinal axons to follow aberrant pathways within the
      retina. Furthermore, retinal axons deviated from their normal pathway and
      extended to cells ectopically expressing SDF-1 within the retina. These data
      suggest that chemokine signaling is both necessary and sufficient for directing
      retinal growth cones within the retina.

PMID- 15716408
TI  - Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber
      synaptic transmission in epileptic brain.
AB  - In the pilocarpine model of temporal lobe epilepsy, mossy fibers coexpress the
      inhibitory transmitter neuropeptide Y (NPY) with glutamate. The effects of
      endogenous and applied NPY on recurrent mossy fiber synaptic transmission were
      investigated with the use of whole-cell voltage-clamp and field recordings in rat
      hippocampal slices. Applied NPY reversibly inhibited synaptic transmission at
      recurrent mossy fiber synapses on dentate granule cells but not at perforant path
      or associational-commissural synapses. It also reduced the frequency of miniature
      EPSCs (mEPSCs) in granule cells from epileptic, but not control, rats and
      depressed granule cell epileptiform activity dependent on the recurrent mossy
      fiber pathway. These actions of NPY were mediated by activation of presynaptic Y2
      receptors. The Y2 receptor antagonist (S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)
      oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2
      [1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]argininamide
      (BIIE0246) not only blocked the effects of NPY but also enhanced recurrent mossy
      fiber synaptic transmission, the frequency of mEPSCs, and the magnitude of mossy
      fiber-evoked granule cell epileptiform activity when applied by itself. Several
      observations supported the selectivity of BIIE0246. These results suggest that
      even the spontaneous release of NPY (or an active metabolite) from recurrent
      mossy fibers is sufficient to depress glutamate release from this pathway. Tonic
      release of NPY accounts at least partially for the low probability of glutamate
      release from recurrent mossy fiber terminals, impedes the ability of these fibers
      to synchronize granule cell discharge, and may protect the hippocampus from
      seizures that involve the entorhinal cortex. This pathway may synchronize granule
      cell discharge more effectively in human brain than in rat because of its lower
      expression of NPY.

PMID- 15716410
TI  - Gq/11-induced and spontaneous waves of coordinated network activation in
      developing frontal cortex.
AB  - Repeated episodes of spontaneous large-scale neuronal bursting and calcium influx
      in the developing brain can potentially affect such fundamental processes as
      circuit formation and gene expression. Between postnatal day 3 (P3) and P7, the
      immature cortex can express one such form of activation whereby a wave of
      neuronal activity propagates through cortical networks, generating massive
      calcium influx. We previously showed that this activity could be triggered by
      brief stimulation of muscarinic receptors. Here, we show, by monitoring large
      cortical areas at low magnification, that although all areas respond to
      muscarinic agonists to some extent, only some areas are likely to generate the
      coordinated wave-like activation. The waves can be triggered repeatedly in
      frontal areas where, as we also show, waves occur spontaneously at a low
      frequency. In parietal and occipital areas, no such waves are seen. This
      selectivity may be related in part to differences in the cortical distribution of
      dopaminergic signaling, because we find that activation of dopamine receptors
      enables the response. Because M1 muscarinic receptors are typically coupled with
      G-alpha(q)/11, we investigated whether other receptors known to couple with this
      G-protein (group I glutamate metabotropic receptors, neurotensin type 1) could
      similarly elicit wave-like activation in responsive cortical areas. Our results
      suggest that multiple neurotransmitter systems can enable this form of activation
      in the frontal cortex. The findings suggest that a poorly recognized,
      developmentally regulated form of strong network activation found predominantly
      in the frontal cortex could potentially exert a profound influence on brain
      development.

PMID- 15716409
TI  - Small-scale molecular motions accomplish glutamate uptake in human glutamate
      transporters.
AB  - Glutamate transporters remove glutamate from the synaptic cleft to maintain
      efficient synaptic communication between neurons and to prevent glutamate
      concentrations from reaching neurotoxic levels. Glutamate transporters play an
      important role in ischemic neuronal death during stroke and have been implicated
      in epilepsy and amytropic lateral sclerosis. However, the molecular structure and
      the glutamate-uptake mechanism of these transporters are not well understood. The
      most recent models of glutamate transporters have three or five subunits, each
      with eight transmembrane domains, and one or two membrane-inserted loops. Here,
      using fluorescence resonance energy transfer (FRET) analysis, we have determined
      the relative position of the extracellular regions of these domains. Our results
      are consistent with a trimeric glutamate transporter with a large (>45 A)
      extracellular vestibule. In contrast to other transport proteins, our FRET
      measurements indicate that there are no large-scale motions in glutamate
      transporters and that glutamate uptake is accompanied by relatively small motions
      around the glutamate-binding sites. The large extracellular vestibule and the
      small-scale conformational changes could contribute to the fast kinetics
      predicted for glutamate transporters. Furthermore, we show that, despite the
      multimeric nature of glutamate transporters, the subunits function independently.

PMID- 15716412
TI  - Spatial exploration-induced Arc mRNA and protein expression: evidence for
      selective, network-specific reactivation.
AB  - The immediate-early gene Arc is transcribed in neurons that are part of stable
      neural networks activated during spatial exploratory behaviors. Arc protein has
      been demonstrated to regulate AMPA-type glutamate receptor trafficking by
      recruiting endosomal pathways, suggesting a direct role in synaptic plasticity.
      The purpose of the present study is to examine the fidelity of Arc mRNA
      translation and the temporal dynamics of behaviorally induced Arc protein
      expression after rats explore a novel environment. These experiments reveal two
      waves of Arc protein expression after a single exploration session. In the
      initial wave, virtually all cells that express Arc mRNA in the hippocampus and
      parietal cortex also express Arc protein, indicating, at a cellular level, that
      mRNA transcription and translation are closely correlated from 30 min to 2 h in
      hippocampal CA and parietal neurons. A second wave of protein expression spans
      the interval from 8 to 24 h and is also remarkably specific to cells active in
      the original behavior-induced network. This second wave is detected in a subset
      of the original active network and displays the novel property that the
      proportions of Arc-positive neurons become correlated among regions at 24 h. This
      suggests that the second expression wave is driven by network activity, and the
      stabilization of circuits reflecting behavioral experience may occur in
      temporally discrete phases, as memories become consolidated. This is the first
      demonstration of network-selective translational events consequent to spatial
      behavior and suggests a role for immediate-early genes in circuit-specific, late
      phase synaptic biology.

PMID- 15716411
TI  - Activity-dependent long-term potentiation of intrinsic excitability in
      hippocampal CA1 pyramidal neurons.
AB  - The efficiency of neural circuits is enhanced not only by increasing synaptic
      strength but also by increasing intrinsic excitability. In contrast to the
      detailed analysis of long-term potentiation (LTP), less attention has been given
      to activity-dependent changes in the intrinsic neuronal excitability. By
      stimulating hippocampal CA1 pyramidal neurons with synaptic inputs correlating
      with postsynaptic neuronal spikes, we elicited an LTP of intrinsic excitability
      (LTP-IE) concurring with synaptic LTP. LTP-IE was manifested as a decrease in the
      action potential threshold that was attributable to a hyperpolarized shift in the
      activation curve of voltage-gated sodium channels (VGSCs) rather than activity
      dependent changes in synaptic inputs or A-type K+ channels. Cell-attached patch
      recording of VGSC activities indicated such an activity-dependent change in
      VGSCs. Induction of LTP-IE was blocked by the NMDA receptor antagonist APV,
      intracellular BAPTA, the CaM kinase inhibitors KN-62 and autocamtide-2-related
      inhibitory peptide, and the protein synthesis inhibitors emetine and anisomycin.
      The results suggest that induction of LTP-IE shares a similar signaling pathway
      with the late phase of synaptic LTP and requires activation of the NMDA glutamate
      receptor subtype, Ca2+ influx, activity of CaM kinase II, and function of the
      protein synthesis. This new form of hippocampal neuronal plasticity could be a
      cellular correlate of learning and memory besides synaptic LTP.

PMID- 15716413
TI  - NADPH-oxidase-derived reactive oxygen species mediate the cerebrovascular
      dysfunction induced by the amyloid beta peptide.
AB  - Overproduction of the amyloid beta (Abeta) peptide is a key factor in the
      pathogenesis of Alzheimer's disease (AD), but the mechanisms of its pathogenic
      effects have not been defined. Patients with AD have cerebrovascular alterations
      attributable to the deleterious effects of Abeta on cerebral blood vessels. We
      report here that NADPH oxidase, the major source of free radicals in blood
      vessels, is responsible for the cerebrovascular dysregulation induced by Abeta.
      Thus, the free-radical production and the associated alterations in
      vasoregulation induced by Abeta are abrogated by the NADPH oxidase peptide
      inhibitor gp91ds-tat and are not observed in mice lacking the catalytic subunit
      of NADPH oxidase (gp91phox). Furthermore, oxidative stress and cerebrovascular
      dysfunction do not occur in transgenic mice overexpressing the amyloid precursor
      protein but lacking gp91phox. The mechanisms by which NADPH oxidase-derived
      radicals mediate the cerebrovascular dysfunction involve reduced bioavailability
      of nitric oxide. Thus, a gp91phox-containing NADPH oxidase is the critical link
      between Abeta and cerebrovascular dysfunction, which may underlie the alteration
      in cerebral blood flow regulation observed in AD patients.

PMID- 15716414
TI  - Triple knock-out of CNTF, LIF, and CT-1 defines cooperative and distinct roles of
      these neurotrophic factors for motoneuron maintenance and function.
AB  - Members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor
      (LIF) gene family play an essential role for survival of developing and postnatal
      motoneurons. When subunits of the shared receptor complex are inactivated by
      homologous recombination, the mice die at approximately birth and exhibit reduced
      numbers of motoneurons in the spinal cord and brainstem nuclei. However, mice in
      which cntf, lif, or cardiotrophin-1 (ct-1) are inactivated can survive and show
      less motoneuron cell loss. This suggests cooperative and redundant roles of these
      ligands. However, their cooperative functions are not well understood. We
      generated cntf/lif/ct-1 triple-knock-out and combinations of double-knock-out
      mice to study the individual and combined roles of CNTF, LIF and CT-1 on
      postnatal motoneuron survival and function. Triple-knock-out mice exhibit
      increased motoneuron cell loss in the lumbar spinal cord that correlates with
      muscle weakness during early postnatal development. LIF deficiency leads to
      pronounced loss of distal axons and motor endplate alterations, whereas CNTF
      and/or CT-1-deficient mice do not show significant changes in morphology of these
      structures. In cntf/lif/ct-1 triple-knock-out mice, various degrees of muscle
      fiber type grouping are found, indicating that denervation and reinnervation had
      occurred. We conclude from these findings that CNTF, LIF, and CT-1 have distinct
      functions for motoneuron survival and function and that LIF plays a more
      important role for postnatal maintenance of distal axons and motor endplates than
      CNTF or CT-1.

PMID- 15716415
TI  - Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during
      endotoxemia, independent of systemic cytokines.
AB  - Inflammatory agonists such as lipopolysaccharide (LPS) induce robust systemic as
      well as CNS responses after peripheral administration. Responses in the innate
      immune system require triggering of toll-like receptor 4 (TLR4), but the origin
      of CNS sequelas has been controversial. We demonstrate expression of TLR4
      transcripts in mouse brain in the meninges, ventricular ependyma,
      circumventricular organs, along the vasculature, and in parenchymal microglia.
      The contribution of TLR4 expressed in CNS resident versus hematopoietic cells to
      the development of CNS inflammation was examined using chimeric mice. Reciprocal
      bone marrow chimeras between wild-type and TLR4 mutant mice show that TLR4 on CNS
      resident cells is critically required for sustained inflammation in the brain
      after systemic LPS administration. Hematopoietic TLR4 alone supported the
      systemic release of acute phase cytokines, but transcription of proinflammatory
      genes in the CNS was reduced in duration. In contrast, TLR4 function in radiation
      resistant cells was sufficient for inflammatory progression in the brains of
      chimeric mice, despite the striking absence of cytokine elevations in serum.
      Surprisingly, a temporal rise in serum corticosterone was also dependent on TLR4
      signaling in nonhematopoietic cells. Our findings demonstrate a requirement for
      TLR4 function in CNS-resident cells, independent of systemic cytokine effects,
      for sustained CNS-specific inflammation and corticosterone rise during
      endotoxemia.

PMID- 15716416
TI  - Phospholipase D1-promoted release of tissue plasminogen activator facilitates
      neurite outgrowth.
AB  - Temporal lobe epilepsy (TLE) is the most common form of epilepsy, affecting
      approximately 1-2% of the population. Seizure events resulting from TLE are
      characterized by aberrant hippocampal mossy fiber sprouting and plastic responses
      that affect brain function. Seizure susceptibility is modulated by the enzyme
      tissue plasminogen activator (tPA), the normal physiological role of which
      includes promotion of synaptic reorganization in the mossy fiber pathway by
      initiating a proteolytic cascade that cleaves extracellular matrix components and
      influences neurite extension. tPA is concentrated at and selectively secreted
      from growth cones during excitatory events. However, the mechanisms underlying
      tPA release during seizure-induced synaptogenesis are not well understood. We
      examine here potential roles for the signaling enzyme phospholipase D1 (PLD1),
      which promotes regulated exocytosis in non-CNS cell types, and which we
      previously demonstrated increases in expression in hippocampal neurons during
      seizure-induced mossy fiber sprouting. We now show that overexpression of wild
      type PLD1 in cultured neurons promotes tPA release and tPA-dependent neurite
      extension, whereas overexpression of an inactive PLD1 allele or pharmacological
      inhibition of PLD1 inhibits tPA release. Similarly, viral delivery of wild-type
      PLD1 into the hippocampus facilitates tPA secretion and mossy fiber sprouting in
      a seizure-inducing model, whereas the inactive PLD1 allele inhibits tPA release
      and elicits blunted and abnormal mossy fiber extension similar to that observed
      for tPA-/- mice. Together, these findings secretion and thus mossy fiber
      extension in the setting of elevated suggest that PLD1 functions endogenously to
      regulate tPA-/- neuronal stimulation, such as that seen in TLE.

PMID- 15716417
TI  - Structural basis for a broad but selective ligand spectrum of a mouse olfactory
      receptor: mapping the odorant-binding site.
AB  - The olfactory receptor (OR) superfamily provides a basis for the remarkable
      ability to recognize and discriminate a large number of odorants. In mice, the
      superfamily includes approximately 1000 members, and they recognize overlapping
      sets of odorants with distinct affinities and specificities. To address the
      molecular basis of odor discrimination by the mammalian OR superfamily, we
      performed functional analysis on a series of site-directed mutants and performed
      ligand docking simulation studies to define the odorant-binding site of a mouse
      OR. Our results indicate that several amino acids in the transmembrane domains
      formed a ligand-binding pocket. Although other G-protein-coupled receptors
      (GPCRs) recognize biogenic ligands mainly with ionic or hydrogen bonding
      interactions, ORs recognize odorants mostly via hydrophobic and van der Waals
      interactions. This accounts for the broad but selective binding by ORs as well as
      their relatively low ligand-binding affinities. Furthermore, we succeeded in
      rational receptor design, inserting point mutations in the odorant-binding site
      that resulted in predicted changes in ligand specificity and antagonist activity.
      This ability to rationally design the receptor validated the binding site
      structure that was deduced with our mutational and ligand docking studies. Such
      broad and specific sensitivity suggests an evolutionary process during which
      mutations in the active site led to an enormous number of ORs with a wide range
      of ligand specificity. The current study reveals the molecular environment of the
      odorant-binding site, and it further advances the understanding of GPCR
      pharmacology.

PMID- 15716418
TI  - Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus
      and induces progenitor cell proliferation.
AB  - The hippocampal dentate gyrus (DG) is an area of active proliferation and
      neurogenesis within the adult brain. The molecular events controlling adult cell
      genesis in the hippocampus essentially remain unknown. It has been reported
      previously that adult male and female rats from the strains Sprague Dawley (SD)
      and spontaneously hypertensive (SHR) have a marked difference in proliferation
      rates of cells in the hippocampal DG. To exploit this natural variability and
      identify potential regulators of cell genesis in the hippocampus, hippocampal
      gene expression from male SHR as well as male and female SD rats was analyzed
      using a cDNA array strategy. Hippocampal expression of the gene-encoding glucose
      dependent insulinotropic polypeptide (GIP) varied strongly in parallel with cell
      proliferation rates in the adult rat DG. Moreover, robust GIP immunoreactivity
      could be detected in the DG. The GIP receptor is expressed by cultured adult
      hippocampal progenitors and throughout the granule cell layer of the DG,
      including progenitor cells. Thus, these cells have the ability to respond to GIP.
      Indeed, exogenously delivered GIP induced proliferation of adult-derived
      hippocampal progenitors in vivo as well as in vitro, and adult GIP receptor knock
      out mice exhibit a significantly lower number of newborn cells in the hippocampal
      DG compared with wild-type mice. This investigation demonstrates the presence of
      GIP in the brain for the first time and provides evidence for a regulatory
      function for GIP in progenitor cell proliferation.

PMID- 15716419
TI  - Hippocampal synaptic modulation by the phosphotyrosine adapter protein ShcC/N-Shc
      via interaction with the NMDA receptor.
AB  - N-Shc (neural Shc) (also ShcC), an adapter protein possessing two phosphotyrosine
      binding motifs [PTB (phosphotyrosine binding) and SH2 (Src homology 2) domains],
      is predominantly expressed in mature neurons of the CNS and transmits
      neurotrophin signals from the TrkB receptor to the Ras/mitogen-activated protein
      kinase (MAPK) pathway, leading to cellular growth, differentiation, or survival.
      Here, we demonstrate a novel role of ShcC, the modulation of NMDA receptor
      function in the hippocampus, using ShcC gene-deficient mice. In behavioral
      analyses such as the Morris water maze, contextual fear conditioning, and novel
      object recognition tasks, ShcC mutant mice exhibited superior ability in
      hippocampus-dependent spatial and nonspatial learning and memory. Consistent with
      this finding, electrophysiological analyses revealed that hippocampal long-term
      potentiation in ShcC mutant mice was significantly enhanced, with no alteration
      of presynaptic function, and the effect of an NMDA receptor antagonist on its
      expression in the mutant mice was notably attenuated. The tyrosine
      phosphorylation of NMDA receptor subunits NR2A and NR2B was also increased,
      suggesting that ShcC mutant mice have enhanced NMDA receptor function in the
      hippocampus. These results indicate that ShcC not only mediates TrkB-Ras/MAPK
      signaling but also is involved in the regulation of NMDA receptor function in the
      hippocampus via interaction with phosphotyrosine residues on the receptor
      subunits and serves as a modulator of hippocampal synaptic plasticity underlying
      learning and memory.

PMID- 15716420
TI  - Mutation of critical GIRK subunit residues disrupts N- and C-termini association
      and channel function.
AB  - The subfamily of G-protein-linked inwardly rectifying potassium channels (GIRKs)
      is coupled to G-protein receptors throughout the CNS and in the heart. We used
      mutational analysis to address the role of a specific hydrophobic region of the
      GIRK1 subunit. Deletion of the GIRK1 C-terminal residues 330-384, as well as the
      point mutation I331R, resulted in a decrease in channel function when coexpressed
      with GIRK4 in oocytes and in COS-7 cells. Surface protein expression of GIRK1
      I331R coexpressed with GIRK4 was comparable with wild type, indicating that
      subunits assemble and are correctly localized to the membrane. Subsequent
      mutation of homologous residues in both the GIRK4 subunit and Kir2.1 (Gbetagamma
      independent inward rectifier) also resulted in a decrease in channel function.
      Intracellular domain associations resulted in the coimmunoprecipitation of the
      GIRK1 N and C termini and GIRK4 N and C termini. The point mutation I331R in the
      GIRK1 C terminus or L337R in the GIRK4 C terminus decreased the association
      between the N and C termini. Mutation of a GIRK1 N-terminal hydrophobic residue,
      predicted structurally to interact with the C-terminal domain, also resulted in a
      decrease in channel function and termini association. We hypothesize that the
      hydrophobic nature of this GIRK1 subunit region is critical for interaction
      between adjacent termini and is permissive for channel gating. In addition, the
      homologous mutation in cytoplasmic domains of Kir2.1 (L330R) did not disrupt
      association, suggesting that the overall structural integrity of this region is
      critical for inward rectifier function.

PMID- 15716421
TI  - Activity-dependent synaptic plasticity in the central nucleus of the amygdala.
AB  - Much evidence indicates that fear conditioning involves potentiation of some
      thalamic inputs to the lateral amygdala (LA). In turn, the LA would excite more
      neurons in the central nucleus (CE), leading to the generation of fear responses
      via their brainstem and hypothalamic projections. However, the posterior thalamus
      not only projects to LA but also to the medial sector of CE (CEm), suggesting
      that CEm might also be a site of plasticity. To test whether CEm also exhibits
      activity-dependent synaptic plasticity, we performed whole-cell recordings of CEm
      neurons in amygdala slices and stimulated thalamic axons coursing through the
      internal capsule and, as a control, the basolateral (BL) nucleus. High-frequency
      stimulation of thalamic inputs led to a long-lasting potentiation of thalamic
      responses, whereas BL-evoked responses remained unchanged. This thalamic long
      term potentiation (LTP) developed even when slices were prepared with a cut
      severing the connections between the LA and CEm but was greatly reduced when an
      NMDA receptor antagonist was added to the perfusate shortly before and during LTP
      induction. Yet, intracellular dialysis with the NMDA receptor antagonist (+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate did not
      prevent induction of the thalamic LTP, suggesting that presynaptic NMDA receptors
      are required for its induction. Consistent with this, the thalamic LTP also
      developed when the cells were dialyzed with a calcium chelator or kept
      hyperpolarized during induction. Finally, this thalamic LTP was associated with
      reduced amounts of paired-pulse facilitation, suggesting that it is expressed
      presynaptically. These results are consistent with the idea that the CEm plays an
      active role in fear conditioning.

PMID- 15716423
TI  - Role of synaptic and intrinsic membrane properties in short-term receptive field
      dynamics in cat area 17.
AB  - We examined the mechanisms through which the prolonged presentation of either a
      high-contrast stimulus or an artificial scotoma [equivalent to the stimulation of
      the receptive field (RF) surround] induces changes in the RF properties of
      neurons intracellularly recorded in cat primary visual cortex. Discharge and
      synaptic RFs were quantitatively characterized using bright and dark bars
      randomly flashed in various positions. Compared with the lack of stimulation (0%
      contrast for 15-30 s), stimulation with high-contrast sine-wave gratings (15-30
      s) was followed by a strong reduction in gain and a weak but significant
      reduction in width of spike discharge RFs. These reductions were accompanied by a
      membrane potential hyperpolarization, a decrease of synaptic RF width, and
      varying changes of synaptic RF gain. Passive hyperpolarization by DC injection
      also produced significant reduction in the width and gain of discharge RF.
      Mimicking, in single neurons, high-contrast stimulation with high-intensity
      current injection also induced a membrane potential hyperpolarization, whose
      amplitude was correlated with discharge RF gain and width changes. Recovery from
      adaptation to high-contrast stimulation during the period of gray screen or
      scotoma presentation was associated with an increase in gain and discharge RF
      size. Stimulation of the RF surround with an artificial scotoma did not have any
      additional aftereffects over those of adaptation to a gray screen, indicating
      that the contraction and expansion of RF gain and size are attributable to
      intrinsic and synaptic mechanisms underlying adaptation and de-adaptation to
      strong visual stimuli.

PMID- 15716422
TI  - Sodium channels in transient retinal bipolar cells enhance visual responses in
      ganglion cells.
AB  - Retinal bipolar cells are slow potential neurons that respond to photoreceptor
      inputs with graded potentials and do not fire action potentials. We found that
      transient ON bipolar cells recorded in retinal slices possess voltage-gated
      sodium channels located on either their dendrites or somas. The sodium currents
      in these neurons did not generate spikes but enhanced voltage responses evoked by
      visual stimulation, which selectively boosted transmission to transient ganglion
      cells. In contrast, sodium currents were not found in sustained ON bipolar cells,
      and light responses in sustained bipolar cells and ganglion cells were not
      affected by TTX. The presence of sodium channels in transient ON bipolar cells
      contributed to the separation of transient and sustained signals by selectively
      enhancing the responses of ON transient ganglion cells to light. Our results
      suggest that bipolar cell sodium channels augment transient signals and
      contribute to the temporal segregation of visual information.

PMID- 15716424
TI  - A novel mechanism for desulfation of mucin: identification and cloning of a mucin
      desulfating glycosidase (sulfoglycosidase) from Prevotella strain RS2.
AB  - A novel enzyme which may be important in mucin degradation has been discovered in
      the mucin-utilizing anaerobe Prevotella strain RS2. This enzyme cleaves terminal
      2-acetamido-2-deoxy-beta-D-glucopyranoside 6-sulfate (6-SO3-GlcNAc) residues from
      sulfomucin and from the model substrate 4-nitrophenyl 2-acetamido-2-deoxy-beta-D
      glucopyranoside 6-sodium sulfate. The existence of this mucin-desulfating
      glycosidase (sulfoglycosidase) suggests an alternative mechanism by which this
      bacterium may desulfate sulfomucins, by glycosidic removal of a sulfated sugar
      from mucin oligosaccharide chains. Previously, mucin desulfation was thought to
      take place by the action of a specific desulfating enzyme, which then allowed
      glycosidases to remove desulfated sugar. Sulfate removal from sulfomucins is
      thought to be a rate-limiting step in mucin degradation by bacteria in the
      regions of the digestive tract with a significant bacterial flora. The
      sulfoglycosidase was induced by growth of the Prevotella strain on mucin and was
      purified 284-fold from periplasmic extracts. Tryptic digestion and sequencing of
      peptides from the 100-kDa protein enabled the sulfoglycosidase gene to be cloned
      and sequenced. Active recombinant enzyme was made in an Escherichia coli
      expression system. The sulfoglycosidase shows sequence similarity to
      hexosaminidases. The only other enzyme that has been shown to remove 6-SO3-GlcNAc
      from glycoside substrates is the human lysosomal enzyme beta-N
      acetylhexosaminidase A, point mutations in which cause the inheritable, lysosomal
      storage disorder Tay-Sachs disease. The human enzyme removes GlcNAc from
      glycoside substrates also, in contrast to the Prevotella enzyme, which acts on a
      nonsulfated substrate at a rate that is only 1% of the rate observed with a
      sulfated substrate.

PMID- 15716425
TI  - Identification of essential amino acid residues of the NorM Na+/multidrug
      antiporter in Vibrio parahaemolyticus.
AB  - NorM is a member of the multidrug and toxic compound extrusion (MATE) family and
      functions as a Na+/multidrug antiporter in Vibrio parahaemolyticus, although the
      underlying mechanism of the Na+/multidrug antiport is unknown. Acidic amino acid
      residues Asp32, Glu251, and Asp367 in the transmembrane region of NorM are
      conserved in one of the clusters of the MATE family. In this study, we
      investigated the role(s) of acidic amino acid residues Asp32, Glu251, and Asp367
      in the transmembrane region of NorM by site-directed mutagenesis. Wild-type NorM
      and mutant proteins with amino acid replacements D32E (D32 to E), D32N, D32K,
      E251D, E251Q, D367A, D367E, D367N, and D367K were expressed and localized in the
      inner membrane of Escherichia coli KAM32 cells, while the mutant proteins with
      D32A, E251A, and E251K were not. Compared to cells with wild-type NorM, cells
      with the mutant NorM protein exhibited reduced resistance to kanamycin,
      norfloxacin, and ethidium bromide, but the NorM D367E mutant was more resistant
      to ethidium bromide. The NorM mutant D32E, D32N, D32K, D367A, and D367K cells
      lost the ability to extrude ethidium ions, which was Na+ dependent, and the
      ability to move Na+, which was evoked by ethidium bromide. Both E251D and D367N
      mutants decreased Na+-dependent extrusion of ethidium ions, but ethidium bromide
      evoked movement of Na+ was retained. In contrast, D367E caused increased
      transport of ethidium ions and Na+. These results suggest that Asp32, Glu251, and
      Asp367 are involved in the Na+-dependent drug transport process.

PMID- 15716426
TI  - Type III secretion of the Salmonella effector protein SopE is mediated via an N
      terminal amino acid signal and not an mRNA sequence.
AB  - Type III secretion systems (TTSS) are virulence-associated components of many
      gram-negative bacteria that translocate bacterial proteins directly from the
      bacterial cytoplasm into the host cell. The Salmonella translocated effector
      protein SopE has no consensus cleavable amino-terminal secretion sequence, and
      the mechanism leading to its secretion through the Salmonella pathogenicity
      island 1 (SPI-1) TTSS is still not fully understood. There is evidence from other
      bacteria which suggests that the TTSS signal may reside within the 5'
      untranslated region (UTR) of the mRNA of secreted effectors. We investigated the
      role of the 5' UTR in the SPI-1 TTSS-mediated secretion of SopE using promoter
      fusions and obtained data indicating that the mRNA sequence is not involved in
      the secretion process. To clarify the proteinaceous versus RNA nature of the
      signal, we constructed frameshift mutations in the amino-terminal region of SopE
      of Salmonella enterica serovar Typhimurium SL1344. Only constructs with the
      native amino acid sequence were secreted, highlighting the importance of the
      amino acid sequence versus the mRNA sequence for secretion. Additionally, we
      obtained frameshift mutation data suggesting that the first 15 amino acids are
      important for secretion of SopE independent of the presence of the chaperone
      binding site. These data shed light on the nature of the signal for SopE
      secretion and highlight the importance of the amino-terminal amino acids for
      correct targeting and secretion of SopE via the SPI-1-encoded TTSS during host
      cell invasion.

PMID- 15716427
TI  - Fis regulates transcriptional induction of RpoS in Salmonella enterica.
AB  - The sigma factor RpoS is known to regulate at least 60 genes in response to
      environmental sources of stress or during growth to stationary phase (SP).
      Accumulation of RpoS relies on integration of multiple genetic controls,
      including regulation at the levels of transcription, translation, protein
      stability, and protein activity. Growth to SP in rich medium results in a 30-fold
      induction of RpoS, although the mechanism of this regulation is not understood.
      We characterized the activity of promoters serving rpoS in Salmonella enterica
      serovar Typhimurium and report that regulation of transcription during growth
      into SP depends on Fis, a DNA-binding protein whose abundance is high during
      exponential growth and very low in SP. A fis mutant of S. enterica serovar
      Typhimurium showed a ninefold increase in expression from the major rpoS promoter
      (PrpoS) during exponential growth, whereas expression during SP was unaffected.
      Increased transcription from PrpoS in the absence of Fis eliminated the
      transcriptional induction as cells enter SP. The mutant phenotype can be
      complemented by wild-type fis carried on a single-copy plasmid. Fis regulation of
      rpoS requires the presence of a Fis site positioned at -50 with respect to PrpoS,
      and this site is bound by Fis in vitro. A model is presented in which Fis binding
      to this site allows repression of rpoS specifically during exponential growth,
      thus mediating transcriptional regulation of rpoS.

PMID- 15716428
TI  - Experimental identification and quantification of glucose metabolism in seven
      bacterial species.
AB  - The structurally conserved and ubiquitous pathways of central carbon metabolism
      provide building blocks and cofactors for the biosynthesis of cellular
      macromolecules. The relative uses of pathways and reactions, however, vary widely
      among species and depend upon conditions, and some are not used at all. Here we
      identify the network topology of glucose metabolism and its in vivo operation by
      quantification of intracellular carbon fluxes from 13C tracer experiments.
      Specifically, we investigated Agrobacterium tumefaciens, two pseudomonads,
      Sinorhizobium meliloti, Rhodobacter sphaeroides, Zymomonas mobilis, and
      Paracoccus versutus, which grow on glucose as the sole carbon source, represent
      fundamentally different metabolic lifestyles (aerobic, anaerobic,
      photoheterotrophic, and chemoheterotrophic), and are phylogenetically distinct
      (firmicutes, gamma-proteobacteria, and alpha-proteobacteria). Compared to those
      of the model bacteria Escherichia coli and Bacillus subtilis, metabolisms of the
      investigated species differed significantly in several respects: (i) the Entner
      Doudoroff pathway was the almost exclusive catabolic route; (ii) the pentose
      phosphate pathway exhibited exclusively biosynthetic functions, in many cases
      also requiring flux through the nonoxidative branch; (iii) all aerobes exhibited
      fully respiratory metabolism without significant overflow metabolism; and (iv)
      all aerobes used the pyruvate bypass of the malate dehydrogenase reaction to a
      significant extent. Exclusively, Pseudomonas fluorescens converted most glucose
      extracellularly to gluconate and 2-ketogluconate. Overall, the results suggest
      that metabolic data from model species with extensive industrial and laboratory
      history are not representative of microbial metabolism, at least not
      quantitatively.

PMID- 15716429
TI  - Genome-wide analysis of the general stress response network in Escherichia coli:
      sigmaS-dependent genes, promoters, and sigma factor selectivity.
AB  - The sigmaS (or RpoS) subunit of RNA polymerase is the master regulator of the
      general stress response in Escherichia coli. While nearly absent in rapidly
      growing cells, sigmaS is strongly induced during entry into stationary phase
      and/or many other stress conditions and is essential for the expression of
      multiple stress resistances. Genome-wide expression profiling data presented here
      indicate that up to 10% of the E. coli genes are under direct or indirect control
      of sigmaS and that sigmaS should be considered a second vegetative sigma factor
      with a major impact not only on stress tolerance but on the entire cell
      physiology under nonoptimal growth conditions. This large data set allowed us to
      unequivocally identify a sigmaS consensus promoter in silico. Moreover, our
      results suggest that sigmaS-dependent genes represent a regulatory network with
      complex internal control (as exemplified by the acid resistance genes). This
      network also exhibits extensive regulatory overlaps with other global regulons
      (e.g., the cyclic AMP receptor protein regulon). In addition, the global
      regulatory protein Lrp was found to affect sigmaS and/or sigma70 selectivity of
      many promoters. These observations indicate that certain modules of the sigmaS
      dependent general stress response can be temporarily recruited by stress-specific
      regulons, which are controlled by other stress-responsive regulators that act
      together with sigma70 RNA polymerase. Thus, not only the expression of genes
      within a regulatory network but also the architecture of the network itself can
      be subject to regulation.

PMID- 15716430
TI  - The metal permease ZupT from Escherichia coli is a transporter with a broad
      substrate spectrum.
AB  - The Escherichia coli zupT (formerly ygiE) gene encodes a cytoplasmic membrane
      protein (ZupT) related to members of the eukaryotic ZIP family of divalent metal
      ion transporters. Previously, ZupT was shown to be responsible for uptake of
      zinc. In this study, we show that ZupT is a divalent metal cation transporter of
      broad substrate specificity. An E. coli strain with a disruption in all known
      iron uptake systems could grow in the presence of chelators only if zupT was
      expressed. Heterologous expression of Arabidopsis thaliana ZIP1 could also
      alleviate iron deficiency in this E. coli strain, as could expression of
      indigenous mntH or feoABC. Transport studies with intact cells showed that ZupT
      facilitates uptake of 55Fe2+ similarly to uptake of MntH or Feo. Other divalent
      cations were also taken up by ZupT, as shown using 57Co2+. Expression of zupT
      rendered E. coli cells hypersensitive to Co2+ and sensitive to Mn2+. ZupT did not
      appear to be metal regulated: expression of a Phi(zupT-lacZ) operon fusion
      indicated that zupT is expressed constitutively at a low level.

PMID- 15716431
TI  - An unusual mutation results in the replacement of diaminopimelate with
      lanthionine in the peptidoglycan of a mutant strain of Mycobacterium smegmatis.
AB  - Mycobacterial peptidoglycan contains L-alanyl-D-iso-glutaminyl-meso
      diaminopimelyl-D-alanyl-D-alanine peptides, with the exception of the
      peptidoglycan of Mycobacterium leprae, in which glycine replaces the L-alanyl
      residue. The third-position amino acid of the peptides is where peptidoglycan
      cross-linking occurs, either between the meso-diaminopimelate (DAP) moiety of one
      peptide and the penultimate D-alanine of another peptide or between two DAP
      residues. We previously described a collection of spontaneous mutants of DAP
      auxotrophic strains of Mycobacterium smegmatis that can grow in the absence of
      DAP. The mutants are grouped into seven classes, depending on how well they grow
      without DAP and whether they are sensitive to DAP, temperature, or detergent.
      Furthermore, the mutants are hypersusceptible to beta-lactam antibiotics when
      grown in the absence of DAP, suggesting that these mutants assemble an abnormal
      peptidoglycan. In this study, we show that one of these mutants, M. smegmatis
      strain PM440, utilizes lanthionine, an unusual bacterial metabolite, in place of
      DAP. We also demonstrate that the abilities of PM440 to grow without DAP and use
      lanthionine for peptidoglycan biosynthesis result from an unusual mutation in the
      putative ribosome binding site of the cbs gene, encoding cystathionine beta
      synthase, an enzyme that is a part of the cysteine biosynthetic pathway.

PMID- 15716432
TI  - Cupin-type phosphoglucose isomerases (Cupin-PGIs) constitute a novel metal
      dependent PGI family representing a convergent line of PGI evolution.
AB  - Cupin-type phosphoglucose isomerases (cPGIs) were identified in some archaeal and
      bacterial genomes and the respective coding function of cpgi's from the
      euryarchaeota Archaeoglobus fulgidus and Methanosarcina mazei, as well as the
      bacteria Salmonella enterica serovar Typhimurium and Ensifer meliloti, was proven
      by functional overexpression. These cPGIs and the cPGIs from Pyrococcus and
      Thermococcus spp. represent the cPGI family and were compared with respect to
      kinetic, inhibitory, thermophilic, and metal-binding properties. cPGIs showed a
      high specificity for the substrates fructose-6-phosphate and glucose-6-phosphate
      and were inhibited by millimolar concentrations of sorbitol-6-phosphate,
      erythrose-4-phosphate, and 6-phosphogluconate. Treatment of cPGIs with EDTA
      resulted in a complete loss of catalytic activity, which could be regained by the
      addition of some divalent cations, most effectively by Fe2+ and Ni2+, indicating
      a metal dependence of cPGI activity. The motifs TX3PX3GXEX3TXGHXHX6-11EXY and
      PPX3HX3N were deduced as the two signature patterns of the novel cPGI family.
      Phylogenetic analysis suggests lateral gene transfer for the bacterial cPGIs from
      euryarchaeota.

PMID- 15716433
TI  - Transcriptional polarity in rRNA operons of Escherichia coli nusA and nusB mutant
      strains.
AB  - Synthesis of ribosomes in Escherichia coli requires an antitermination system
      that modifies RNA polymerase to achieve efficient transcription of the genes
      specifying 16S, 23S, and 5S rRNA. This modification requires nucleotide signals
      in the RNA and specific transcription factors, such as NusA and NusB.
      Transcription of rrn operons in strains lacking the ability to produce either
      NusA or NusB was examined by electron microscopy. The distribution and numbers of
      RNA polymerase molecules on rrn operons were determined for each mutant. Compared
      to the wild type, the 16S gene in the nusB mutant strain had an equivalent number
      of RNA polymerase molecules, but the number of RNA polymerase molecules was
      reduced 1.4-fold for the nusA mutant. For both mutant strains, there were twofold
      fewer RNA polymerase molecules on the 23S RNA gene than for the wild type.
      Overall, the mutant strains each had 1.6-fold-fewer RNA polymerase molecules on
      their rrn operons than did the wild type. To determine if decreased transcription
      of the 23S gene observed by electron microscopy also affected the 30S/50S
      ribosomal subunit ratio, ribosome profiles were examined by sucrose gradient
      analysis. The 30S/50S ratio increased 2.5- to 3-fold for the nus mutant strains
      over that for wild-type cells. Thus, strains carrying either a nusA mutation or a
      nusB mutation have defects in transcription of 23S rRNA.

PMID- 15716434
TI  - Genotyping Mycobacterium ulcerans and Mycobacterium marinum by using
      mycobacterial interspersed repetitive units.
AB  - A novel category of variable tandem repeats (VNTR) called mycobacterial
      interspersed repetitive units (MIRUs) has been identified for Mycobacterium
      ulcerans (n = 39), M. marinum (n = 27), and one related organism. Fifteen MIRU
      loci were identified in the genome of M. marinum and were used to genotype M.
      ulcerans, M. marinum, and an M. marinum-like organism that is considered a
      possible missing link between M. marinum and M. ulcerans. Seven MIRU loci were
      polymorphic, and locus-specific PCRs for four of these loci differentiated seven
      M. ulcerans genotypes, four M. marinum genotypes, and a unique genotype for the
      missing link organism. The seven M. ulcerans genotypes were related to six
      different geographic origins of isolates. All isolates from West and Central
      Africa, including old and recent isolates, belonged to the same genotype,
      emphasizing the great spatiotemporal homogeneity among African isolates. Unlike
      the M. ulcerans genotypes, the four M. marinum genotypes could not be clearly
      related to the geographic origins of the isolates. According to MIRU-VNTR typing,
      all M. ulcerans and M. marinum isolates of American origin were closely related,
      suggesting a common American ancestor for these two pathogenic species on the
      American continents. MIRU typing has significant potential value for
      discriminating between reoccurrence and reinfection for M. ulcerans disease.

PMID- 15716435
TI  - Activation of the vrg6 promoter of Bordetella pertussis by RisA.
AB  - The BvgAS two-component system positively regulates the expression of the
      virulence genes of Bordetella pertussis and negatively regulates a second set of
      genes whose function is unknown. The BvgAS-mediated regulation of the bvg
      repressed genes is accomplished through the activation of expression of the
      negative regulator, BvgR. A second two-component regulatory system, RisAS, is
      required for expression of the bvg-repressed surface antigens VraA and VraB. We
      examined the roles of BvgR and RisA in the regulation of four bvg-repressed genes
      in B. pertussis. Our analyses demonstrated that all four genes are repressed by
      the product of the bvgR locus and are activated by the product of the risA locus.
      Deletion analysis of the vrg6 promoter identified the upstream and downstream
      boundaries of the promoter and, in contrast to previously published results,
      demonstrated that sequences downstream of the start of transcription are not
      required for the regulation of expression of vrg6. Gel mobility-shift experiments
      demonstrated sequence-specific binding of RisA to the vrg6 and vrg18 promoters,
      and led to the identification of two putative RisA binding sites. Finally,
      transcriptional analysis and Western blot analysis demonstrated that BvgR
      regulates neither the expression nor the stability of RisA.

PMID- 15716436
TI  - Genomic analysis of anaerobic respiration in the archaeon Halobacterium sp.
      strain NRC-1: dimethyl sulfoxide and trimethylamine N-oxide as terminal electron
      acceptors.
AB  - We have investigated anaerobic respiration of the archaeal model organism
      Halobacterium sp. strain NRC-1 by using phenotypic and genetic analysis,
      bioinformatics, and transcriptome analysis. NRC-1 was found to grow on either
      dimethyl sulfoxide (DMSO) or trimethylamine N-oxide (TMAO) as the sole terminal
      electron acceptor, with a doubling time of 1 day. An operon, dmsREABCD, encoding
      a putative regulatory protein, DmsR, a molybdopterin oxidoreductase of the DMSO
      reductase family (DmsEABC), and a molecular chaperone (DmsD) was identified by
      bioinformatics and confirmed as a transcriptional unit by reverse transcriptase
      PCR analysis. dmsR, dmsA, and dmsD in-frame deletion mutants were individually
      constructed. Phenotypic analysis demonstrated that dmsR, dmsA, and dmsD are
      required for anaerobic respiration on DMSO and TMAO. The requirement for dmsR,
      whose predicted product contains a DNA-binding domain similar to that of the Bat
      family of activators (COG3413), indicated that it functions as an activator. A
      cysteine-rich domain was found in the dmsR gene, which may be involved in oxygen
      sensing. Microarray analysis using a whole-genome 60-mer oligonucleotide array
      showed that the dms operon is induced during anaerobic respiration. Comparison of
      dmsR+ and DeltadmsR strains by use of microarrays showed that the induction of
      the dmsEABCD operon is dependent on a functional dmsR gene, consistent with its
      action as a transcriptional activator. Our results clearly establish the genes
      required for anaerobic respiration using DMSO and TMAO in an archaeon for the
      first time.

PMID- 15716437
TI  - Common evolutionary origin for the unstable virulence plasmid pMUM found in
      geographically diverse strains of Mycobacterium ulcerans.
AB  - The 174-kb virulence plasmid pMUM001 in Mycobacterium ulcerans epidemic strain
      Agy99 harbors three very large and homologous genes that encode giant polyketide
      synthases (PKS) responsible for the synthesis of the lipid toxin mycolactone.
      Deeper investigation of M. ulcerans Agy99 resulted in identification of two types
      of spontaneous deletion variants of pMUM001 within a population of cells that
      also contained the intact plasmid. These variants arose from recombination
      between two 8-kb sections of the same plasmid sequence, resulting in the loss of
      a 65-kb region bearing two of the three mycolactone PKS genes. Investigation of
      nine diverse M. ulcerans strains by using PCR and Southern hybridization for
      eight pMUM001 gene sequences confirmed the presence of pMUM001-like elements
      (collectively called pMUM) in all M. ulcerans strains. Physical mapping of these
      plasmids revealed that like M. ulcerans Agy99, three strains had undergone major
      deletions in their mycolactone PKS loci. Online liquid chromatography-sequential
      mass spectrometry analysis of lipid extracts confirmed that strains with PKS
      deletions were unable to produce mycolactone or any related cometabolites.
      Interstrain comparisons of the plasmid gene sequences revealed greater than 98%
      nucleotide identity, and the phylogeny inferred from these sequences closely
      mimicked the phylogeny from a previous multilocus sequence typing study in which
      chromosomally encoded loci were used, a result that is consistent with the
      hypothesis that M. ulcerans diverged from the closely related organism
      Mycobacterium marinum by acquiring pMUM. Our results suggest that pMUM is a
      defining characteristic of M. ulcerans but that in the absence of purifying
      selection, deletion of plasmid sequences and a corresponding loss of mycolactone
      production readily arise.

PMID- 15716439
TI  - Two novel phycoerythrin-associated linker proteins in the marine cyanobacterium
      Synechococcus sp. strain WH8102.
AB  - The recent availability of the whole genome of Synechococcus sp. strain WH8102
      allows us to have a global view of the complex structure of the phycobilisomes of
      this marine picocyanobacterium. Genomic analyses revealed several new
      characteristics of these phycobilisomes, consisting of an allophycocyanin core
      and rods made of one type of phycocyanin and two types of phycoerythrins (I and
      II). Although the allophycocyanin appears to be similar to that found commonly in
      freshwater cyanobacteria, the phycocyanin is simpler since it possesses only one
      complete set of alpha and beta subunits and two rod-core linkers (CpcG1 and
      CpcG2). It is therefore probably made of a single hexameric disk per rod. In
      contrast, we have found two novel putative phycoerythrin-associated linker
      polypeptides that appear to be specific for marine Synechococcus spp. The first
      one (SYNW2000) is unusually long (548 residues) and apparently results from the
      fusion of a paralog of MpeC, a phycoerythrin II linker, and of CpeD, a
      phycoerythrin-I linker. The second one (SYNW1989) has a more classical size (300
      residues) and is also an MpeC paralog. A biochemical analysis revealed that, like
      MpeC, these two novel linkers were both chromophorylated with phycourobilin. Our
      data suggest that they are both associated (partly or totally) with phycoerythrin
      II, and we propose to name SYNW2000 and SYNW1989 MpeD and MpeE, respectively. We
      further show that acclimation of phycobilisomes to high light leads to a dramatic
      reduction of MpeC, whereas the two novel linkers are not significantly affected.
      Models for the organization of the rods are proposed.

PMID- 15716438
TI  - Compiling a molecular inventory for Mycobacterium bovis BCG at two growth rates:
      evidence for growth rate-mediated regulation of ribosome biosynthesis and lipid
      metabolism.
AB  - An experimental system of Mycobacterium tuberculosis growth in a carbon-limited
      chemostat has been established by the use of Mycobacterium bovis BCG as a model
      organism. For this model, carbon-limited chemostats with low concentrations of
      glycerol were used to simulate possible growth rates during different stages of
      tuberculosis. A doubling time of 23 h (D = 0.03 h(-1)) was adopted to represent
      cells during the acute phase of infection, whereas a lower dilution rate
      equivalent to a doubling time of 69 h (D = 0.01 h(-1)) was used to model
      mycobacterial persistence. This chemostat model allowed the specific response of
      the mycobacterial cell to carbon limitation at different growth rates to be
      elucidated. The macromolecular (RNA, DNA, carbohydrate, and lipid) and elemental
      (C, H, and N) compositions of the biomass were determined for steady-state
      cultures, revealing that carbohydrates and lipids comprised more than half of the
      dry mass of the BCG cell, with only a quarter of the dry weight consisting of
      protein and RNA. Consistent with studies of other bacteria, the specific growth
      rate impacts on the macromolecular content of BCG and the proportions of lipid,
      RNA, and protein increased significantly with the growth rate. The correlation of
      RNA content with the growth rate indicates that ribosome production in carbon
      limited M. bovis BCG cells is subject to growth rate-dependent control. The
      results also clearly show that the proportion of lipids in the mycobacterial cell
      is very sensitive to changes in the growth rate, probably reflecting changes in
      the amounts of storage lipids. Finally, this study demonstrates the utility of
      the chemostat model of mycobacterial growth for functional genomic, physiology,
      and systems biology studies.

PMID- 15716440
TI  - A chimeric N-terminal Escherichia coli--C-terminal Rhodobacter sphaeroides FliG
      rotor protein supports bidirectional E. coli flagellar rotation and chemotaxis.
AB  - Flagellate bacteria such as Escherichia coli and Salmonella enterica serovar
      Typhimurium typically express 5 to 12 flagellar filaments over their cell surface
      that rotate in clockwise (CW) and counterclockwise directions. These bacteria
      modulate their swimming direction towards favorable environments by biasing the
      direction of flagellar rotation in response to various stimuli. In contrast,
      Rhodobacter sphaeroides expresses a single subpolar flagellum that rotates only
      CW and responds tactically by a series of biased stops and starts. Rotor protein
      FliG transiently links the MotAB stators to the rotor, to power rotation and also
      has an essential function in flagellar export. In this study, we sought to
      determine whether the FliG protein confers directionality on flagellar motors by
      testing the functional properties of R. sphaeroides FliG and a chimeric FliG
      protein, EcRsFliG (N-terminal and central domains of E. coli FliG fused to an R.
      sphaeroides FliG C terminus), in an E. coli FliG null background. The EcRsFliG
      chimera supported flagellar synthesis and bidirectional rotation; bacteria swam
      and tumbled in a manner qualitatively similar to that of the wild type and showed
      chemotaxis to amino acids. Thus, the FliG C terminus alone does not confer the
      unidirectional stop-start character of the R. sphaeroides flagellar motor, and
      its conformation continues to support tactic, switch-protein interactions in a
      bidirectional motor, despite its evolutionary history in a bacterium with a
      unidirectional motor.

PMID- 15716441
TI  - Structural and spectroscopic properties of a reaction center complex from the
      chlorosome-lacking filamentous anoxygenic phototrophic bacterium Roseiflexus
      castenholzii.
AB  - The photochemical reaction center (RC) complex of Roseiflexus castenholzii, which
      belongs to the filamentous anoxygenic phototrophic bacteria (green filamentous
      bacteria) but lacks chlorosomes, was isolated and characterized. The genes coding
      for the subunits of the RC and the light-harvesting proteins were also cloned and
      sequenced. The RC complex was composed of L, M, and cytochrome subunits. The
      cytochrome subunit showed a molecular mass of approximately 35 kDa, contained
      hemes c, and functioned as the electron donor to the photo-oxidized special pair
      of bacteriochlorophylls in the RC. The RC complex appeared to contain three
      molecules of bacteriochlorophyll and three molecules of bacteriopheophytin, as in
      the RC preparation from Chloroflexus aurantiacus. Phylogenetic trees based on the
      deduced amino acid sequences of the RC subunits suggested that R. castenholzii
      had diverged from C. aurantiacus very early after the divergence of filamentous
      anoxygenic phototrophic bacteria from purple bacteria. Although R. castenholzii
      is phylogenetically related to C. aurantiacus, the arrangement of its puf genes,
      which code for the light-harvesting proteins and the RC subunits, was different
      from that in C. aurantiacus and similar to that in purple bacteria. The genes are
      found in the order pufB, -A, -L, -M, and -C, with the pufL and pufM genes forming
      one continuous open reading frame. Since the photosynthetic apparatus and genes
      of R. castenholzii have intermediate characteristics between those of purple
      bacteria and C. aurantiacus, it is likely that they retain many features of the
      common ancestor of purple bacteria and filamentous anoxygenic phototrophic
      bacteria.

PMID- 15716442
TI  - The core lipopolysaccharide of Escherichia coli is a ligand for the dendritic
      cell-specific intercellular adhesion molecule nonintegrin CD209 receptor.
AB  - The dendritic-cell-specific intercellular adhesion molecule nonintegrin (DC-SIGN)
      CD209 is a receptor for Escherichia coli K-12 that promotes bacterial adherence
      and phagocytosis. However, the ligand of E. coli for DC-SIGN has not yet been
      identified. In this study, we found that DC-SIGN did not mediate the phagocytosis
      of several pathogenic strains of E. coli, including enteropathogenic E. coli,
      enterohemorrhagic E. coli, enterotoxigenic E. coli, and uropathogenic E. coli, in
      dendritic cells or HeLa cells expressing human DC-SIGN antigen. However, we
      showed that an outer core lipopolysaccharide (LPS) (rough) mutant, unlike an
      inner core LPS (deep rough) mutant or O-antigen-expressing recombinant of E. coli
      K-12 was phagocytosed. These results demonstrate that the host cells expressing
      DC-SIGN can phagocytose E. coli in part by interacting with the complete core
      region of the LPS molecule. These results provide a mechanism for how O antigen
      acts as an antiphagocytic factor.

PMID- 15716443
TI  - Divergent regulatory pathways control A and S motility in Myxococcus xanthus
      through FrzE, a CheA-CheY fusion protein.
AB  - Myxococcus xanthus moves on solid surfaces by using two gliding motility systems,
      A motility for individual-cell movement and S motility for coordinated group
      movements. The frz genes encode chemotaxis homologues that control the cellular
      reversal frequency of both motility systems. One of the components of the core
      Frz signal transduction pathway, FrzE, is homologous to both CheA and CheY from
      the enteric bacteria and is therefore a novel CheA-CheY fusion protein. In this
      study, we investigated the role of this fusion protein, in particular, the CheY
      domain (FrzECheY). FrzECheY retains all of the highly conserved residues of the
      CheY superfamily of response regulators, including Asp709, analogous to
      phosphoaccepting Asp57 of Escherichia coli CheY. While in-frame deletion of the
      entire frzE gene caused both motility systems to show a hyporeversal phenotype,
      in-frame deletion of the FrzECheY domain resulted in divergent phenotypes for the
      two motility systems: hyperreversals of the A-motility system and hyporeversals
      of the S-motility system. To further investigate the role of FrzECheY in A and S
      motility, point mutations were constructed such that the putative
      phosphoaccepting residue, Asp709, was changed from D to A (and was therefore
      never subject to phosphorylation) or E (possibly mimicking constitutive
      phosphorylation). The D709A mutant showed hyperreversals for both motilities,
      while the D709E mutant showed hyperreversals for A motility and hyporeversal for
      S motility. These results show that the FrzECheY domain plays a critical
      signaling role in coordinating A and S motility. On the basis of the phenotypic
      analyses of the frzE mutants generated in this study, a model is proposed for the
      divergent signal transduction through FrzE in controlling and coordinating A and
      S motility in M. xanthus.

PMID- 15716444
TI  - Additional determinants within Escherichia coli FNR activating region 1 and RNA
      polymerase alpha subunit required for transcription activation.
AB  - The global anaerobic regulator FNR is a DNA binding protein that activates
      transcription of genes required for anaerobic metabolism in Escherichia coli
      through interactions with RNA polymerase (RNAP). Alanine-scanning mutagenesis of
      FNR amino acid residues 181 to 193 of FNR was utilized to determine which amino
      acid side chains are required for transcription of both class II and class I
      promoters. In vivo assays of FNR function demonstrated that a core of residues
      (F181, R184, S187, and R189) was required for efficient activation of class II
      promoters, while at a class I promoter, FF(-61.5), only S187 and R189 were
      critical for FNR activation. Site-directed mutagenesis of positions 184, 187, and
      189 revealed that the positive charge contributes to the function of the side
      chain at positions 184 and 189 while the serine hydroxyl is critical for the
      function of position 187. Subsequent analysis of the carboxy-terminal domain of
      the alpha subunit (alphaCTD) of RNAP, using an alanine library in single copy,
      revealed that in addition to previously characterized side chains (D305, R317,
      and L318), E286 and E288 contributed to FNR activation of both class II and class
      I promoters, suggesting that alphaCTD region 285 to 288 also participates in
      activation by FNR. In conclusion, this study demonstrates that multiple side
      chains within region 181 to 192 are required for FNR activation and the surface
      of alphaCTD required for FNR activation is more extensive than previously
      observed.

PMID- 15716445
TI  - Multiple extracellular loops contribute to substrate binding and transport by the
      Escherichia coli cobalamin transporter BtuB.
AB  - The Escherichia coli outer membrane TonB-dependent transporters for iron
      complexes and cobalamins recognize their multiple and diverse substrates with
      high specificity and affinity. The X-ray crystallographic structures of several
      transporters show that the substrate-binding surfaces are comprised of residues
      from the internal globular domain and multiple extracellular loops. The
      extracellular loops on the N-terminal half of the transmembrane beta-barrel of
      the cobalamin transporter BtuB participate in binding of the cofactor calcium
      atoms and undergo substantial conformation changes upon substrate binding. The
      functional relevance of the five C-terminal loops was examined by examining the
      effects of short in-frame deletions. Each loop contributed in different ways to
      the binding of BtuB substrates. Deletions in loops 7, 8, 9, and 11 strongly
      decreased cobalamin binding and transport, whereas deletions in loops 8, 9, and
      10 affected binding and entry of phage BF23. None of the loops were essential for
      the action of colicin E1 or E3, which is consistent with the crystallographic
      observation that the colicin E3 receptor-binding domain can contact almost all of
      the loops. A deletion in loop 9 or 11 eliminated the ability of cobalamin to
      inhibit the action of colicin E1. These phenotypes show that there are multiple
      independent binding elements and point out similarities and differences in
      binding properties among the TonB-dependent transporters.

PMID- 15716446
TI  - Comparative study of class 1 integron and Vibrio cholerae superintegron integrase
      activities.
AB  - Superintegrons (SIs) and multiresistant integrons (MRIs) have two main structural
      differences: (i) the SI platform is sedentary, while the MRI platform is commonly
      associated with mobile DNA elements and (ii) the recombination sites (attC) of SI
      gene cassette clusters are highly homogeneous, while those of MRI cassette arrays
      are highly variable in length and sequence. In order to determine if the latter
      difference was correlated with a dissimilarity in the recombination activities,
      we conducted a comparative study of the integron integrases of the class 1 MRI
      (IntI1) and the Vibrio cholerae SI (VchIntIA). We developed two assays that
      allowed us to independently measure the frequencies of cassette deletion and
      integration at the cognate attI sites. We demonstrated that the range of attC
      sites efficiently recombined by VchIntIA is narrower than the range of attC sites
      efficiently recombined by IntI1. Introduction of mutations into the V. cholerae
      repeats (VCRs), the attC sites of the V. cholerae SI cassettes, allowed us to map
      positions that affected the VchIntIA and IntI1 activities to different extents.
      Using a cointegration assay, we established that in E. coli, attI1-x-VCR
      recombination catalyzed by IntI1 was 2,600-fold more efficient than attIVch-x-VCR
      recombination catalyzed by VchIntIA. We performed the same experiments in V.
      cholerae and established that the attIVch-x-VCR recombination catalyzed by
      VchIntIA was 2,000-fold greater than the recombination measured in E. coli. Taken
      together, our results indicate that in the V. cholerae SI, the substrate
      recognition and recombination reactions mediated by VchIntIA might differ from
      the class 1 MRI paradigm.

PMID- 15716447
TI  - Cytoplasmic control of premature activation of a secreted protease zymogen:
      deletion of staphostatin B (SspC) in Staphylococcus aureus 8325-4 yields a
      profound pleiotropic phenotype.
AB  - The cytoplasmic protein SspC of Staphylococcus aureus, referred to as
      staphostatin B, is a very specific, tightly binding inhibitor of the secreted
      protease staphopain B (SspB). SspC is hypothesized to protect intracellular
      proteins against proteolytic damage by prematurely folded and activated
      staphopain B (M. Rzychon, A. Sabat, K. Kosowska, J. Potempa, and A. Dubin, Mol.
      Microbiol. 49:1051-1066, 2003). Here we provide evidence that elimination of
      intracellular staphopain B activity is indeed the function of SspC. An isogenic
      sspC mutant of S. aureus 8325-4 exhibits a wide range of striking pleiotropic
      alterations in phenotype, which distinguish it from the parent. These changes
      include a defect in growth, a less structured peptidoglycan layer within the cell
      envelope, severely decreased autolytic activity, resistance to lysis by S. aureus
      phages, extensively diminished sensitivity to lysis by lysostaphin, the ability
      to form a biofilm, and a total lack of extracellular proteins secreted into the
      growth media. The same phenotype was also engineered by introduction of sspB into
      an 8325-4 sspBC mutant. In contrast, sspC inactivation in the SH1000 strain did
      not yield any significant changes in the mutant phenotype, apparently due to
      strongly reduced expression of sspB in the sigma B-positive background. The exact
      pathway by which these diverse aberrations are exerted in 8325-4 is unknown, but
      it is apparent that a very small amount of staphopain B (less than 20 ng per 200
      microg of cell proteins) is sufficient to bring about these widespread changes.
      It is proposed that the effects observed are modulated through the proteolytic
      degradation of several cytoplasmic proteins within cells lacking the inhibitor.
      Seemingly, some of these proteins may play a role in protein secretion; hence,
      their proteolytic inactivation by SspB has pleiotropic effects on the SspC
      deficient mutant.

PMID- 15716448
TI  - Genome-wide analyses of Escherichia coli gene expression responsive to the BaeSR
      two-component regulatory system.
AB  - The BaeSR two-component regulatory system controls expression of exporter genes
      conferring drug resistance in Escherichia coli (S. Nagakubo, K. Nishino, T.
      Hirata, and A. Yamaguchi, J. Bacteriol. 184:4161-4167, 2002; N. Baranova and H.
      Nikaido, J. Bacteriol. 184:4168-4176, 2002). To understand the whole picture of
      BaeSR regulation, a DNA microarray analysis of the effect of BaeR overproduction
      was performed. BaeR overproduction activated 59 genes related to two-component
      signal transduction, chemotactic responses, flagellar biosynthesis, maltose
      transport, and multidrug transport, and BaeR overproduction also repressed the
      expression of the ibpA and ibpB genes. All of the changes in the expression
      levels were also observed by quantitative real-time reverse transcription-PCR
      analysis. The expression levels of 15 of the 59 BaeR-activated genes were
      decreased by deletion of baeSR. Of 11 genes induced by indole (a putative inducer
      of the BaeSR system), 10 required the BaeSR system for induction. Combination of
      the expression data sets revealed a BaeR-binding site sequence motif, 5'
      TTTTTCTCCATDATTGGC-3' (where D is G, A, or T). Several genes up-regulated by BaeR
      overproduction, including genes for maltose transport, chemotactic responses, and
      flagellar biosynthesis, required an intact PhoBR or CreBC two-component
      regulatory system for up-regulation. These data indicate that there is cross
      regulation among the BaeSR, PhoBR, and CreBC two-component regulatory systems.
      Such a global analysis should reveal the regulatory network of the BaeSR system.

PMID- 15716449
TI  - Structure of the nucleotide complex of PyrR, the pyr attenuation protein from
      Bacillus caldolyticus, suggests dual regulation by pyrimidine and purine
      nucleotides.
AB  - PyrR is a protein that regulates the expression of genes and operons of
      pyrimidine nucleotide biosynthesis (pyr genes) in many bacteria. PyrR acts by
      binding to specific sequences on pyr mRNA and causing transcriptional attenuation
      when intracellular levels of uridine nucleotides are elevated. PyrR from Bacillus
      subtilis has been purified and extensively studied. In this work, we describe the
      purification to homogeneity and characterization of recombinant PyrR from the
      thermophile Bacillus caldolyticus and the crystal structures of unliganded PyrR
      and a PyrR-nucleotide complex. The B. caldolyticus pyrR gene was previously shown
      to restore normal regulation of the B. subtilis pyr operon in a pyrR deletion
      mutant. Like B. subtilis PyrR, B. caldolyticus PyrR catalyzes the uracil
      phosphoribosyltransferase reaction but with maximal activity at 60 degrees C.
      Crystal structures of B. caldolyticus PyrR reveal a dimer similar to the B.
      subtilis PyrR dimer and, for the first time, binding sites for nucleotides. UMP
      and GMP, accompanied by Mg2+, bind specifically to PyrR active sites. Nucleotide
      binding to PyrR is similar to other phosphoribosyltransferases, but Mg2+ binding
      differs. GMP binding was unexpected. The protein bound specific sequences of pyr
      RNA 100 to 1,000 times more tightly than B. subtilis PyrR, depending on the RNA
      tested and the assay method; uridine nucleotides enhanced RNA binding, but
      guanosine nucleotides antagonized it. The new findings of specific GMP binding
      and its antagonism of RNA binding suggest cross-regulation of the pyr operon by
      purines.

PMID- 15716450
TI  - Evolution of genomic content in the stepwise emergence of Escherichia coli
      O157:H7.
AB  - Genome comparisons have demonstrated that dramatic genetic change often underlies
      the emergence of new bacterial pathogens. Evolutionary analysis of Escherichia
      coli O157:H7, a pathogen that has emerged as a worldwide public health threat in
      the past two decades, has posited that this toxin-producing pathogen evolved in a
      series of steps from O55:H7, a recent ancestor of a nontoxigenic pathogenic clone
      associated with infantile diarrhea. We used comparative genomic hybridization
      with 50-mer oligonucleotide microarrays containing probes from both pathogenic
      and nonpathogenic genomes to infer when genes were acquired and lost. Many
      ancillary virulence genes identified in the O157 genome were already present in
      an O55:H7-like progenitor, with 27 of 33 genomic islands of >5 kb and specific
      for O157:H7 (O islands) that were acquired intact before the split from this
      immediate ancestor. Most (85%) of variably absent or present genes are part of
      prophages or phage-like elements. Divergence in gene content among these closely
      related strains was approximately 140 times greater than divergence at the
      nucleotide sequence level. A >100-kb region around the O-antigen gene cluster
      contained highly divergent sequences and also appears to be duplicated in its
      entirety in one lineage, suggesting that the whole region was cotransferred in
      the antigenic shift from O55 to O157. The beta-glucuronidase-positive O157
      variants, although phylogenetically closest to the Sakai strain, were divergent
      for multiple adherence factors. These observations suggest that, in addition to
      gains and losses of phage elements, O157:H7 genomes are rapidly diverging and
      radiating into new niches as the pathogen disseminates.

PMID- 15716451
TI  - Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: insights into
      biochemistry of the GGDEF protein domain.
AB  - Proteins containing GGDEF domains are encoded in the majority of sequenced
      bacterial genomes. In several species, these proteins have been implicated in
      biosynthesis of exopolysaccharides, formation of biofilms, establishment of a
      sessile lifestyle, surface motility, and regulation of gene expression. However,
      biochemical activities of only a few GGDEF domain proteins have been tested.
      These proteins were shown to be involved in either synthesis or hydrolysis of
      cyclic-bis(3'-->5') dimeric GMP (c-di-GMP) or in hydrolysis of cyclic AMP. To
      investigate specificity of the GGDEF domains in Bacteria, six GGDEF domain
      encoding genes from randomly chosen representatives of diverse branches of the
      bacterial phylogenetic tree, i.e., Thermotoga, Deinococcus-Thermus,
      Cyanobacteria, spirochetes, and alpha and gamma divisions of the Proteobacteria,
      were cloned and overexpressed. All recombinant proteins were purified and found
      to possess diguanylate cyclase (DGC) activity involved in c-di-GMP synthesis. The
      individual GGDEF domains from two proteins were overexpressed, purified, and
      shown to possess a low level of DGC activity. The oligomeric states of full
      length proteins and individual GGDEF domains were similar. This suggests that
      GGDEF domains are sufficient to encode DGC activity; however, enzymatic activity
      is highly regulated by the adjacent sensory protein domains. It is shown that DGC
      activity of the GGDEF domain protein Rrp1 from Borrelia burgdorferi is strictly
      dependent on phosphorylation status of its input receiver domain. This study
      establishes that majority of GGDEF domain proteins are c-di-GMP specific, that c
      di-GMP synthesis is a wide-spread phenomenon in Bacteria, and that it is highly
      regulated.

PMID- 15716452
TI  - Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system,
      the QSI selector.
AB  - With the widespread appearance of antibiotic-resistant bacteria, there is an
      increasing demand for novel strategies to control infectious diseases.
      Furthermore, it has become apparent that the bacterial life style also
      contributes significantly to this problem. Bacteria living in the biofilm mode of
      growth tolerate conventional antimicrobial treatments. The discovery that many
      bacteria use quorum-sensing (QS) systems to coordinate virulence and biofilm
      development has pointed out a new, promising target for antimicrobial drugs. We
      constructed a collection of screening systems, QS inhibitor (QSI) selectors,
      which enabled us to identify a number of novel QSIs among natural and synthetic
      compound libraries. The two most active were garlic extract and 4-nitro-pyridine
      N-oxide (4-NPO). GeneChip-based transcriptome analysis revealed that garlic
      extract and 4-NPO had specificity for QS-controlled virulence genes in
      Pseudomonas aeruginosa. These two QSIs also significantly reduced P. aeruginosa
      biofilm tolerance to tobramycin treatment as well as virulence in a
      Caenorhabditis elegans pathogenesis model.

PMID- 15716453
TI  - Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and
      cell wall cross-linking of Staphylococcus aureus: evidence for the cooperative
      functioning of PBP2, PBP4, and PBP2A.
AB  - Ceftizoxime, a beta-lactam antibiotic with high selective affinity for penicillin
      binding protein 2 (PBP2) of Staphylococcus aureus, was used to select a
      spontaneous resistant mutant of S. aureus strain 27s. The stable resistant mutant
      ZOX3 had an increased ceftizoxime MIC and a decreased affinity of its PBP2 for
      ceftizoxime and produced peptidoglycan in which the proportion of highly cross
      linked muropeptides was reduced. The pbpB gene of ZOX3 carried a single C-to-T
      nucleotide substitution at nucleotide 1373, causing replacement of a proline with
      a leucine at amino acid residue 458 of the transpeptidase domain of the protein,
      close to the SFN conserved motif. Experimental proof that this point mutation was
      responsible for the drug-resistant phenotype, and also for the decreased PBP2
      affinity and reduced cell wall cross-linking, was provided by allelic replacement
      experiments and site-directed mutagenesis. Disruption of pbpD, the structural
      gene of PBP4, in either the parental strain or the mutant caused a large decrease
      in the highly cross-linked muropeptide components of the cell wall and in the
      mutant caused a massive accumulation of muropeptide monomers as well. Disruption
      of pbpD also caused increased sensitivity to ceftizoxime in both the parental
      cells and the ZOX3 mutant, while introduction of the plasmid-borne mecA gene, the
      genetic determinant of the beta-lactam resistance protein PBP2A, had the opposite
      effects. The findings provide evidence for the cooperative functioning of two
      native S. aureus transpeptidases (PBP2 and PBP4) and an acquired transpeptidase
      (PBP2A) in staphylococcal cell wall biosynthesis and susceptibility to
      antimicrobial agents.

PMID- 15716454
TI  - Light-induced carotenogenesis in Streptomyces coelicolor A3(2): identification of
      an extracytoplasmic function sigma factor that directs photodependent
      transcription of the carotenoid biosynthesis gene cluster.
AB  - Carotenoids are produced by a variety of organisms, but the mechanisms that
      regulate gene expression leading to carotenoid biosynthesis have been
      characterized for only a few organisms. In this study, we found that Streptomyces
      coelicolor A3(2), a gram-positive filamentous bacterium, produces carotenoids
      under blue light induction. The carotenoid fraction isolated from the cell
      extract contained multiple compounds, including isorenieratene and beta-carotene.
      The carotenoid biosynthesis gene cluster of S. coelicolor consists of two
      convergent operons, crtEIBV and crtYTU, as previously shown for Streptomyces
      griseus. The crtEIBV null mutant completely lost its ability to produce
      carotenoids. The crt gene cluster is flanked by a regulatory region that consists
      of two divergent operons, litRQ and litSAB. The lit (light-induced transcription)
      genes encode a MerR-type transcriptional regulator (LitR), a possible
      oxidoreductase (LitQ), an extracytoplasmic function sigma factor (sigmaLitS), a
      putative lipoprotein (LitA), and a putative anti-sigma factor (LitB). S1
      protection assay revealed that the promoters preceding crtE (PcrtE), crtY
      (PcrtY), litR (PlitR), and litS (PlitS) are activated upon illumination. A litS
      mutant lost both the ability to produce carotenoids and the activities of PcrtE,
      PcrtY, and PlitS, which suggested that sigmaLitS directs light-induced
      transcription from these promoters. An RNA polymerase holocomplex containing
      purified sigmaLitS recombinant protein generated specific PcrtE and PcrtY
      transcripts in an in vitro runoff transcriptional assay. A litR mutant that had
      an insertion of the kanamycin resistance gene was defective both in the ability
      to produce carotenoids and in all of the light-dependent promoter activities.
      Overexpression of litS resulted in constitutive carotenoid production in both the
      wild type and the litR mutant. These results indicate that sigmaLitS acts as a
      light-induced sigma factor that directs transcription of the crt biosynthesis
      gene cluster, whose activity is controlled by an unknown LitR function. This is
      the first report to describe light-inducible gene expression in Streptomyces.

PMID- 15716455
TI  - Crystal structures of the BlaI repressor from Staphylococcus aureus and its
      complex with DNA: insights into transcriptional regulation of the bla and mec
      operons.
AB  - The 14-kDa BlaI protein represses the transcription of blaZ, the gene encoding
      beta-lactamase. It is homologous to MecI, which regulates the expression of mecA,
      the gene encoding the penicillin binding protein PBP2a. These genes mediate
      resistance to beta-lactam antibiotics in staphylococci. Both repressors can bind
      either bla or mec DNA promoter-operator sequences. Regulated resistance genes are
      activated via receptor-mediated cleavage of the repressors. Cleavage is induced
      when beta-lactam antibiotics bind the extramembrane sensor of the sensor
      transducer signaling molecules, BlaR1 or MecR1. The crystal structures of BlaI
      from Staphylococcus aureus, both in free form and in complex with 32 bp of DNA of
      the mec operator, have been determined to 2.0- and 2.7-A resolutions,
      respectively. The structure of MecI, also in free form and in complex with the
      bla operator, has been previously reported. Both repressors form homodimers, with
      each monomer composed of an N-terminal DNA binding domain of winged helix-turn
      helix topology and a C-terminal dimerization domain. The structure of BlaI in
      complex with the mec operator shows a protein-DNA interface that is conserved
      between both mec and bla targets. The recognition helix alpha3 interacts
      specifically with the conserved TACA/TGTA DNA binding motif. BlaI and, probably,
      MecI dimers bind to opposite faces of the mec DNA double helix in an up-and-down
      arrangement, whereas MecI and, probably, BlaI dimers bind to the same DNA face of
      bla promoter-operator DNA. This is due to the different spacing of mec and bla
      DNA binding sites. Furthermore, the flexibility of the dimeric proteins may make
      the C-terminal proteolytic cleavage site more accessible when the repressors are
      bound to DNA than when they are in solution, suggesting that the induction
      cascade involves bound rather than free repressor.

PMID- 15716456
TI  - DNA bridging: a property shared among H-NS-like proteins.
AB  - The nucleoid-associated protein H-NS is thought to play an essential role in the
      organization of bacterial chromatin in Escherichia coli. Homologues, often with
      very low sequence identity, are found in most gram-negative bacteria. Microscopic
      analysis reveals that, despite limited sequence identity, their structural
      organization results in similar DNA binding properties.

PMID- 15716457
TI  - The promoter region rather than its downstream inverted repeat sequence is
      responsible for low-level transcription of the thermostable direct hemolysin
      related hemolysin (trh) gene of Vibrio parahaemolyticus.
AB  - We determined the transcriptional start site of the thermostable direct hemolysin
      related hemolysin gene (trh) of Vibrio parahaemolyticus by using a PCR-based
      method and identified the promoter. Mutagenic analysis indicated that the
      promoter-bearing region rather than its downstream inverted repeat sequence was
      responsible for the low-revel of trh transcription.

PMID- 15716458
TI  - DNA content and nucleoid distribution in Methanothermobacter thermautotrophicus.
AB  - Flow cytometry and epifluorescence microscopy results for the euryarchaeon
      Methanothermobacter thermautotrophicus were consistent with filaments containing
      multiple cells. Filaments of one to four cells contained two to eight nucleoids.
      Single chromosome-containing cells were not observed. Filaments containing
      multiple genome copies displayed synchronous DNA replication initiation.
      Chromosome segregation occurred during replication or rapidly after replication
      termination.

PMID- 15716459
TI  - Polyphosphate:AMP phosphotransferase as a polyphosphate-dependent nucleoside
      monophosphate kinase in Acinetobacter johnsonii 210A.
AB  - We have cloned the gene for polyphosphate:AMP phosphotransferase (PAP), the
      enzyme that catalyzes phosphorylation of AMP to ADP at the expense of
      polyphosphate [poly(P)] in Acinetobacter johnsonii 210A. A genomic DNA library
      was constructed in Escherichia coli, and crude lysates of about 6,000 clones were
      screened for PAP activity. PAP activity was evaluated by measuring ATP produced
      by the coupled reactions of PAP and purified E. coli poly(P) kinases (PPKs). In
      this coupled reaction, PAP produces ADP from poly(P) and AMP, and the resulting
      ADP is converted to ATP by PPK. The isolated pap gene (1,428 bp) encodes a
      protein of 475 amino acids with a molecular mass of 55.8 kDa. The C-terminal
      region of PAP is highly homologous with PPK2 homologs isolated from Pseudomonas
      aeruginosa PAO1. Two putative phosphate-binding motifs (P-loops) were also
      identified. The purified PAP enzyme had not only strong PAP activity but also
      poly(P)-dependent nucleoside monophosphate kinase activity, by which it converted
      ribonucleoside monophosphates and deoxyribonucleoside monophosphates to
      ribonucleoside diphosphates and deoxyribonucleoside diphosphates, respectively.
      The activity for AMP was about 10 times greater than that for GMP and 770 and
      about 1,100 times greater than that for UMP and CMP.

PMID- 15716460
TI  - Transcriptome of Treponema pallidum: gene expression profile during experimental
      rabbit infection.
AB  - RNA transcript levels in the syphilis spirochete Treponema pallidum subsp.
      pallidum (Nichols) isolated from experimentally infected rabbits were determined
      by the use of DNA microarray technology. This characterization of the T. pallidum
      transcriptome during experimental infection provides further insight into the
      importance of gene expression levels for the survival and pathogenesis of this
      bacterium.

PMID- 15716461
TI  - Involvement of P1 adhesin in gliding motility of Mycoplasma pneumoniae as
      revealed by the inhibitory effects of antibody under optimized gliding
      conditions.
AB  - To examine the participation of P1 adhesin in gliding of Mycoplasma pneumoniae,
      we examined the effects of an anti-P1 monoclonal antibody on individual gliding
      mycoplasmas. The antibody reduced the gliding speed and removed the gliding cells
      from the glass over time in a concentration-dependent manner but had only a
      slight effect on nongliding cells, suggesting that the conformational changes of
      P1 adhesin and its displacement are involved in the gliding mechanism.

PMID- 15716462
TI  - The Met852 residue is a key organizer of the ligand-binding cavity of the human
      mineralocorticoid receptor.
AB  - Spirolactones harboring various C7 substituents are aldosterone antagonists, and
      some of them are used in the treatment of essential hypertension. They bind to
      the human mineralocorticoid receptor and render it transcriptionally inactive.
      Structural analysis using a three-dimensional homology model of the ligand
      binding domain of the receptor has revealed that the Met852 residue of the ligand
      binding cavity faces the C7 substituent of spirolactones. We therefore tested the
      binding capacities of C7-substituted spirolactones in an in vitro system
      expressing either the mutant receptor, in which Met852 was replaced by alanine,
      or the wild-type receptor. The M852A mutation had almost no effect on the binding
      of C7-substituted spirolactones to mineralocorticoid receptor but dramatically
      reduced the capacity of the receptor to bind steroids with no C7 substituent
      (aldosterone, cortisol, deoxycorticosterone, and canrenone). cis-trans
      Cotransfection assays revealed that two spirolactones characterized by having a
      propyl group [7 alpha-propyl-17 alpha-hydroxy-3-oxo-preg-4-ene-21-carboxylic acid
      gamma-lactone (RU26752)] or a thioacetyl group (spironolactone) at the C7
      position acquired agonist properties when bound to the mutant receptor. In
      contrast, mexrenone and eplerenone, both of which harbor an acetyl group at the
      C7 position, retained antagonist properties when bound to the mutant receptor.
      Overall, these findings indicate that Met852 acts as an organizer residue that
      plays two major roles: 1) it allows steroids with no substituent at the C7
      position to be accommodated within the ligand-binding cavity; and 2) it is
      involved in the steric hindrance that prevents C7-substituted spirolactones from
      folding the receptor in its active state.

PMID- 15716463
TI  - The effect of hydroxylamine on KATP channels in vascular smooth muscle and
      underlying mechanisms.
AB  - Hydroxylamine (HA) is a putative intermediate in the conversion of l-arginine to
      nitric oxide (NO). HA was reported to cause the relaxation of precontracted aorta
      strips; however, the ionic mechanisms of HA-induced vasorelaxation were not yet
      known. In the present study, the whole-cell patch-clamp technique was used to
      examine the effects of HA on ATP-sensitive K+ (K(ATP)) currents and membrane
      potentials in vascular smooth muscle cells from rat mesenteric arteries and
      underlying mechanisms. It was found that bath-applied HA reversibly enhanced
      K(ATP) currents in a concentration-dependent fashion with an EC50 of 54 +/- 3.4
      microM and hyperpolarized the cell membrane from -48 +/- 5.2 to -65 +/- 7.5 mV (n
      = 6, p < 0.01). The increase in K(ATP) currents induced by HA was suppressed by
      superoxide dismutase (-380 +/- 45 to -160 +/- 20 pA, n = 4, p < 0.01) and N
      acetyl-L-cysteine (-385 +/- 55 to -150 +/- 16 pA, n = 5, p < 0.01), indicating
      the involvement of different free radicals, including superoxide anion.
      Hypoxanthine/xanthine oxidase increased not only basal K(ATP) currents, but also
      HA-enhanced K(ATP) currents (from -355 +/- 40 to -480 +/- 62 pA, n = 6, p <
      0.05). Sodium nitroprusside, a spontaneous NO donor, and a membrane-permeable
      cGMP analog (8-bromo-cGMP) were without effects on HA-enhanced K(ATP) currents or
      basal K(ATP) currents. Our results indicate that HA augmented K(ATP) channel
      activity and hyperpolarized cell membrane, possibly via increased free radical
      generation.

PMID- 15716464
TI  - A synthetic derivative of the natural product rocaglaol is a potent inhibitor of
      cytokine-mediated signaling and shows neuroprotective activity in vitro and in
      animal models of Parkinson's disease and traumatic brain injury.
AB  - Many acute and chronic neurodegenerative diseases are characterized by a
      localized inflammatory response and constitutive activation of the transcription
      factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) as
      well as their upstream activating signaling cascades. Ample evidence indicates
      the implication of these processes in the pathogenesis of several diseases of the
      central nervous system. In this study, we show that a synthetic derivative of the
      natural product rocaglaol (compound A) displays potent anti-inflammatory
      properties in human endothelial and murine glial cells in vitro. Compound A
      inhibited cytokine- and lipopolysaccharide-induced release of various
      cytokines/chemokines and of nitric oxide as well as expression of the adhesion
      molecule endothelial leukocyte adhesion molecule-1 and the inducible enzymes
      nitric-oxide synthase and cyclooxygenase-2. As shown by immunocytochemistry and
      immunoblotting, compound A inhibited NF-kappa B and AP-1 activity in mixed glial
      cultures. Compound A exhibited neuroprotective activity in vitro and in vivo. 1
      Methyl-4-phenylpyridinium-induced damage of mesencephalic dopaminergic neurons
      was significantly decreased, and long-term treatment of 1-methyl-4-phenyl
      1,2,3,6,-tetrahydropyridine-injected mice with compound A significantly and dose
      dependently reduced dopaminergic neuronal cell death. In addition, shortterm
      application of compound A to rats suffering from traumatic brain injury induced
      by subdural hematoma resulted in a significant reduction of the cerebral infarct
      volume. These results suggest that by inhibiting NF-kappa B and AP-1 signaling,
      compound A is able to reduce tissue inflammation and neuronal cell death,
      resulting in significant neuroprotection in animal models of neurodegeneration.

PMID- 15716466
TI  - Identification and characterization of binding properties of Helicobacter pylori
      by glycoconjugate arrays.
AB  - The microaerophilic bacterium Helicobacter pylori is well established for its
      role in development of different gastric diseases. Bacterial adhesins and
      corresponding binding sites on the epithelial surface allow H. pylori to colonize
      the gastric tissue. In this investigation, the adhesion of H. pylori to dot blot
      arrays of natural glycoproteins and neoglycoproteins was studied. Adhesion was
      detected by overlay with fluorescence-labeled bacteria on immobilized
      (neo)glycoproteins. The results confirmed the interaction between the adhesin
      BabA and the H-1-, Lewis b-, and related fucose-containing antigens. In addition,
      H. pylori bound to terminal alpha2-3-linked sialic acids as previously described.
      The use of a sabA mutant and sialidase treatment of glycoconjugate arrays showed
      that the adherence of H. pylori to laminin is mediated by the sialic acid-binding
      adhesin, SabA. The adhesion to salivary mucin MUC5B is mainly associated with the
      BabA adhesin and to a lesser extent with the SabA adhesin. This agrees with
      reports, that MUC5B carries both fucosylated blood group antigens and alpha2-3
      linked sialic acids. The adhesion of H. pylori to fibronectin and lactoferrin
      persisted in the babA/sabA double mutant. Because binding to these molecules was
      abolished by denaturation rather than by deglycosylation, it was suggested to
      depend on the recognition of unknown receptor moieties by an additional unknown
      bacterial surface component. The results demonstrate that the bacterial overlay
      method on glycoconjugate arrays is a useful tool for exploration and the
      characterization of unknown adhesin specificities of H. pylori and other
      bacteria.

PMID- 15716465
TI  - Identification and characterization of a functional TATA box polymorphism of the
      UDP glucuronosyltransferase 1A7 gene.
AB  - UDP glucuronosyltransferases (UGT) detoxify bilirubin and therapeutic drugs, a
      process influenced by single nucleotide polymorphisms (SNPs) in their structural
      genes and promoter elements. UGT1A1*28 is a functional UGT promoter polymorphism
      associated with Gilbert's disease and severe irinotecan toxicity, which also
      occurs in the absence of UGT1A1*28. The aim of this study was to identify and
      characterize UGT promoter variants relevant for irinotecan detoxification.
      Recombinant UGT1A proteins were analyzed for irinotecan metabolite
      glucuronidation by UGT activity assays. In 427 healthy blood donors and 71
      homozygous UGT1A1*28 carriers, the 5'-untranslated region of the UGT1A7 gene
      locus was studied. An SNP was detected by allelic discrimination and
      characterized by reporter gene experiments. A novel -57 T--> G SNP with a gene
      frequency of 0.39 in healthy blood donors was identified in the putative TATA box
      of the UGT1A7 gene, reducing promoter activity to 30%. It is in linkage
      dysequilibrium with a variant of the UGT1A7 first exon that is present in the
      reduced-activity UGT1A7*3 and UGT1A7*4 alleles. Homozygous UGT1A1*28 carriers
      simultaneously carried this variant in 97%. We identified a novel reduced
      function TATA box SNP of the UGT1A7 gene that catalyzes irinotecan metabolite
      detoxification. Its association with variants of the UGT1A1 promoter and UGT1A7
      gene may influence irinotecan metabolism. Our finding emphasizes the importance
      of combinations of structural and regulatory gene polymorphisms that may be
      useful as markers of drug toxicity.

PMID- 15716467
TI  - The pattern of nucleotide difference at individual codons among mouse, rat, and
      human.
AB  - The patterns of nucleotide difference were compared at 3,473,111 codons from
      9,390 aligned orthologous genes of mouse (Mus musculus), rat (Rattus norvegicus),
      and human (Homo sapiens). The results showed evidence of a higher frequency of
      both synonymous and nonsynonymous differences from human in the rat than in the
      mouse. However, contrary to a previous report, there was no evidence of a greater
      frequency of codons with multiple nonsynonymous substitutions between the two
      rodent species than expected under random substitution.

PMID- 15716468
TI  - Cross-modal binding and activated attentional networks during audio-visual speech
      integration: a functional MRI study.
AB  - We evaluated the neural substrates of cross-modal binding and divided attention
      during audio-visual speech integration using functional magnetic resonance
      imaging. The subjects (n = 17) were exposed to phonemically concordant or
      discordant auditory and visual speech stimuli. Three different matching tasks
      were performed: auditory-auditory (AA), visual-visual (VV) and auditory-visual
      (AV). Subjects were asked whether the prompted pair were congruent or not. We
      defined the neural substrates for the within-modal matching tasks by VV-AA and AA
      VV. We defined the cross-modal area as the intersection of the loci defined by AV
      AA and AV-VV. The auditory task activated the bilateral anterior superior
      temporal gyrus and superior temporal sulcus, the left planum temporale and left
      lingual gyrus. The visual task activated the bilateral middle and inferior
      frontal gyrus, right occipito-temporal junction, intraparietal sulcus and left
      cerebellum. The bilateral dorsal premotor cortex, posterior parietal cortex
      (including the bilateral superior parietal lobule and the left intraparietal
      sulcus) and right cerebellum showed more prominent activation during AV compared
      with AA and VV. Within these areas, the posterior parietal cortex showed more
      activation during concordant than discordant stimuli, and hence was related to
      cross-modal binding. Our results indicate a close relationship between cross
      modal attentional control and cross-modal binding during speech reading.

PMID- 15716469
TI  - Attention to simultaneous unrelated auditory and visual events: behavioral and
      neural correlates.
AB  - The cognitive and neural bases of the ability to focus attention on information
      in one sensory modality while ignoring information in another remain poorly
      understood. We hypothesized that bimodal selective attention results from
      increased activity in corresponding sensory cortices with a suppression of
      activity in non-corresponding sensory cortices. In a functional magnetic
      resonance imaging (fMRI) study, we presented melodies and shapes alone (unimodal)
      or simultaneously (bimodal). Subjects monitored for changes in an attended
      modality while ignoring the other. Subsequently, memory for both attended and
      unattended stimuli was tested. Subjects remembered attended stimuli equally well
      in unimodal and bimodal conditions, and significantly better than ignored stimuli
      in bimodal conditions. When a subject focused on a stimulus, the blood-oxygen
      level-dependent (BOLD) response increased in sensory cortices corresponding to
      that modality in both unimodal and bimodal conditions. Additionally, the BOLD
      response decreased in sensory cortices corresponding to the non-presented
      modality in unimodal conditions and the unattended modality in bimodal
      conditions. We conclude that top-down attentional effects modulate the
      interaction of sensory cortical areas by gating sensory input. This interaction
      between sensory cortices enhances processing of one modality at the expense of
      the other during selective attention, and subsequently affects memory encoding.

PMID- 15716470
TI  - Cortical control of visually guided reaching: evidence from patients with optic
      ataxia.
AB  - The dorsal stream of visual information processing connecting V1 to the parietal
      cortex is thought to provide a fast control of visually guided reaching.
      Important for this assumption was the observation that in both the monkey and the
      human, parietal lesions may provoke disturbance of visually goal-directed hand
      movements. In the human, severe misreaching termed 'optic ataxia' has been
      ascribed to lesions of the superior parietal lobule (SPL) and/or the
      intraparietal sulcus. Using new tools for lesion analysis, here we re-evaluated
      this view investigating the typical lesion location in a large group of
      unilateral stroke patients with optic ataxia, collected over a time period of 15
      years. We found no evidence for the assumption that disruption of visually guided
      reaching in humans is associated with a lesion typically centering on the SPL on
      the convexity. In both left and right hemispheres, we found optic ataxia
      associated with a lesion overlap that affected the lateral cortical convexity at
      the occipito-parietal junction, i.e. the junction between the inferior parietal
      lobule (IPL) and superior occipital cortex and--in the left hemisphere even more
      posteriorly--also the junction between occipital cortex and the SPL. Via the
      underlying parietal white matter, the lesion overlap extended in both hemispheres
      to the medial cortical aspect, where it affected the precuneus close to the
      occipito-parietal junction. These lateral and medial structures seem to be
      integral to the fast control of visually guided reaching in humans.

PMID- 15716472
TI  - Limited protection of the primary visual cortex from the effects of monocular
      deprivation by strabismus.
AB  - Competition between the two eyes for synaptic space is thought to play a crucial
      role in the developmental plasticity of ocular dominance in the primary visual
      cortex. This competition should be disrupted if geniculocortical afferents from
      the two eyes are spatially segregated. In kittens, strabismus was induced in one
      eye before the onset of the critical period; the effects of a brief period of
      monocular deprivation (MD) at the height of the critical period and subsequent
      recovery were assessed in a longitudinal study employing optical imaging of
      intrinsic signals. Results were compared with those from a control group without
      strabismus. MD caused a substantial loss of cortical territory dominated by the
      deprived eye in all animals. However, in the strabismic animals this loss was
      smaller than in the control group for the hemisphere contralateral to the
      deprived eye. When the deprived eye was reopened, recovery of cortical territory
      was remarkably rapid in all kittens, and close to pre-deprivation responses were
      attained within 3-4 days of reopening. However, kittens without strabismus
      exhibited a greater rate of recovery from MD. Moreover, recovery of visual
      acuity, as assessed by visually evoked potential (VEP) measurements, was slower
      and less complete in animals with strabismus prior to MD. Therefore, strabismus
      does not provide lasting protection against the effects of MD.

PMID- 15716471
TI  - The rise and fall of priming: how visual exposure shapes cortical representations
      of objects.
AB  - How does the amount of time for which we see an object influence the nature and
      content of its cortical representation? To address this question, we varied the
      duration of initial exposure to visual objects and then measured functional
      magnetic resonance imaging (fMRI) signal and behavioral performance during a
      subsequent repeated presentation of these objects. We report a novel 'rise-and
      fall' pattern relating exposure duration and the corresponding magnitude of fMRI
      cortical signal. Compared with novel objects, repeated objects elicited maximal
      cortical response reduction when initially presented for 250 ms. Counter
      intuitively, initially seeing an object for a longer duration significantly
      reduced the magnitude of this effect. This 'rise-and-fall' pattern was also
      evident for the corresponding behavioral priming. To account for these findings,
      we propose that the earlier interval of an exposure to a visual stimulus results
      in a fine-tuning of the cortical response, while additional exposure promotes
      selection of a subset of key features for continued representation. These two
      independent mechanisms complement each other in shaping object representations
      with experience.

PMID- 15716473
TI  - Physiological dissociation in hippocampal subregions in response to amygdala
      stimulation.
AB  - Previous studies indicated that the amygdala, when activated by emotional or
      electrical stimulation, modulates hippocampal-dependent memory processes and
      synaptic plasticity. Although the modulatory effect of the amygdala has often
      been generalized to the hippocampal formation, studies suggest that hippocampal
      subregions may display distinct functional profiles and may respond distinctively
      to amygdala activation. In this study we assessed the effect of basolateral
      amygdala (BLA) stimulation on long-term potentiation (LTP)--a synaptic model of
      memory--induced by a standard (sdTS) or a strong theta stimulation (sgTS) in the
      hippocampal dentate gyrus (DG) and CA1, in anesthetized rats. The modulatory
      stimulation was applied 30 s before or after the tetanus stimulation. Results
      show that while BLA activation impaired CA1 LTP induced with an sdTS, it enhanced
      LTP in the DG under both sdTS and sgTS conditions. These findings provide
      evidence for a differential amygdalar control of hippocampal memory subsystems,
      and may contribute to the understanding of the complexity of memory processes
      under stressful conditions.

PMID- 15716474
TI  - Developmental changes in mental arithmetic: evidence for increased functional
      specialization in the left inferior parietal cortex.
AB  - Arithmetic reasoning is arguably one of the most important cognitive skills a
      child must master. Here we examine neurodevelopmental changes in mental
      arithmetic. Subjects (ages 8-19 years) viewed arithmetic equations and were asked
      to judge whether the results were correct or incorrect. During two-operand
      addition or subtraction trials, for which accuracy was comparable across age,
      older subjects showed greater activation in the left parietal cortex, along the
      supramarginal gyrus and adjoining anterior intra-parietal sulcus as well as the
      left lateral occipital temporal cortex. These age-related changes were not
      associated with alterations in gray matter density, and provide novel evidence
      for increased functional maturation with age. By contrast, younger subjects
      showed greater activation in the prefrontal cortex, including the dorsolateral
      and ventrolateral prefrontal cortex and the anterior cingulate cortex, suggesting
      that they require comparatively more working memory and attentional resources to
      achieve similar levels of mental arithmetic performance. Younger subjects also
      showed greater activation of the hippocampus and dorsal basal ganglia, reflecting
      the greater demands placed on both declarative and procedural memory systems. Our
      findings provide evidence for a process of increased functional specialization of
      the left inferior parietal cortex in mental arithmetic, a process that is
      accompanied by decreased dependence on memory and attentional resources with
      development.

PMID- 15716475
TI  - Case study: weight of evidence evaluation of the human health relevance of
      thiamethoxam-related mouse liver tumors.
AB  - Thiamethoxam (CGA293343; 3-(2-chloro-thiazol-5-ylmethyl)-5-methyl
      [1,3,5]oxadiazinan-4-ylidene-N-nitroamine) was shown to increase the incidence of
      mouse liver tumors in an 18-month study; however, thiamethoxam was not
      hepatocarcinogenic in rats. Thiamethoxam is not genotoxic, and, given the late
      life generation of mouse liver tumors, suggests a time-related progression of key
      hepatic events that leads to the tumors. These key events were identified in a
      series of studies of up to 50 weeks that showed the time-dependent evolution of
      relatively mild liver dysfunction within 10 weeks of dosing, followed by frank
      signs of hepatotoxicity after 20 weeks, leading to cellular attrition and
      regenerative hyperplasia. A metabolite, CGA330050, was identified as generating
      the mild hepatic toxicity, and another metabolite, CGA265307, exacerbated the
      initial toxicity by inhibiting inducible nitric oxide synthase. This combination
      of metabolite-generated hepatotoxicity and increase in cell replication rates is
      postulated as the mode of action for thiamethoxam-related mouse liver tumors. The
      relevance of these mouse-specific tumors to human health was assessed by using
      the framework and decision logic developed by ILSI-RSI. The postulated mode of
      action was tested against the Hill criteria and found to fulfill the
      comprehensive requirements of strength, consistency, specificity, temporality,
      dose-response, and the collective criteria of being a plausible mode of action
      that fits with known and similar modes of action. Whereas the postulated mode of
      action could theoretically operate in human liver, quantitation of the key
      metabolites in vivo and in vitro showed that mice, but not rats or humans,
      generate sufficient amounts of these metabolites to initiate the hepatic toxicity
      and consequent tumors. Indeed, rats fed 3000 ppm thiamethoxam for a lifetime did
      not develop hepatotoxicity or tumors. In conclusion, the coherence and extent of
      the database clearly demonstrates the mode of action for mouse liver
      tumorigenesis and also allows for the conclusion that thiamethoxam does not pose
      a carcinogenic risk to humans.

PMID- 15716476
TI  - Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 2:
      species differences in response.
AB  - Thiamethoxam is a neonicotinoid insecticide that is not a mutagen, but it did
      cause a significant increase in liver cancer in mice, but not rats, in chronic
      dietary feeding studies. Previous studies in mice have characterized a
      carcinogenicity mode of action that involved depletion of plasma cholesterol,
      cell death, both as single cell necrosis and as apoptosis, and sustained
      increases in cell replication rates. In a study reported in this article, female
      rats have been exposed to thiamethoxam in their diet at concentrations of 0,
      1000, and 3000 ppm for 50 weeks, a study design directly comparable to the mouse
      study in which the mode of action changes were characterized. In rats,
      thiamethoxam had no adverse effects on either the biochemistry or histopathology
      of the liver at any time point during the study. Cell replication rates were not
      increased, in fact they were significantly decreased at several time points. The
      lack of effect on the rat liver is entirely consistent with the lack of liver
      tumor formation in the two-year cancer bioassay. Comparisons of the metabolism of
      thiamethoxam in rats and mice have shown that concentrations of the parent
      chemical were either similar or higher in rat blood than in mouse blood in both
      single dose and the dietary studies strongly indicating that thiamethoxam itself
      is unlikely to play a role in the development of liver tumors. In contrast, the
      concentrations of the two metabolites, CGA265307 and CGA330050, shown to play a
      role in the development of liver damage in the mouse, were 140- (CGA265307) and
      15- (CGA330050) fold lower in rats than in mice following either a single oral
      dose, or dietary administration of thiamethoxam for up to 50 weeks. Comparisons
      of the major metabolic pathways of thiamethoxam in vitro using mouse, rat, and
      human liver fractions have shown that metabolic rates in humans are lower than
      those in the rat suggesting that thiamethoxam is unlikely to pose a hazard to
      humans exposed to this chemical at the low concentrations found in the
      environment or during its use as an insecticide.

PMID- 15716477
TI  - Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 1:
      mode of action studies in the mouse.
AB  - Thiamethoxam, a neonicotinoid insecticide, which is not mutagenic either in vitro
      or in vivo, caused an increased incidence of liver tumors in mice when fed in the
      diet for 18 months at concentrations in the range 500 to 2500 ppm. A number of
      dietary studies of up to 50 weeks duration have been conducted in order to
      identify the mode of action for the development of the liver tumors seen at the
      end of the cancer bioassay. Both thiamethoxam and its major metabolites have been
      tested in these studies. Over the duration of a 50-week thiamethoxam dietary
      feeding study in mice, the earliest change, within one week, is a marked
      reduction (by up to 40%) in plasma cholesterol. This was followed 10 weeks later
      by evidence of liver toxicity including single cell necrosis and an increase in
      apoptosis. After 20 weeks there was a significant increase in hepatic cell
      replication rates. All of these changes persisted from the time they were first
      observed until the end of the study at 50 weeks. They occurred in a dose
      dependent manner and were only observed at doses (500, 1250, 2500 ppm) where
      liver tumors were increased in the cancer bioassay. There was a clear no-effect
      level of 200 ppm. The changes seen in this study are consistent with the
      development of liver cancer in mice and form the basis of the mode of action.
      When the major metabolites of thiamethoxam, CGA322704, CGA265307, and CGA330050
      were tested in dietary feeding studies of up to 20 weeks duration, only
      metabolite CGA330050 induced the same changes as those seen in the liver in the
      thiamethoxam feeding study. It was concluded that thiamethoxam is hepatotoxic and
      hepatocarcinogenic as a result of its metabolism to CGA330050. Metabolite
      CGA265307 was also shown to be an inhibitor of inducible nitric oxide synthase
      and to increase the hepatotoxicity of carbon tetrachloride. It is proposed that
      CGA265307, through its effects on nitric oxide synthase, exacerbates the toxicity
      of CGA330050 in thiamethoxam treated mice.

PMID- 15716478
TI  - Divergent roles for glutathione in lindane-induced acute and delayed-onset
      inhibition of rat myometrial gap junctions.
AB  - Previous studies have shown that the insecticide lindane (gamma
      hexachlorocyclohexane) induces a biphasic inhibition of gap junction
      intercellular communication that is accompanied by oxidative stress. The present
      study investigates the hypothesis that depletion of cellular glutathione (GSH) is
      a mechanistic link between lindane-induced oxidative stress and inhibition of
      myometrial gap junctions. Exposure to 100 or 200 microM lindane rapidly (within 1
      min) increased myometrial cell generation of superoxide, as measured by
      superoxide dismutase-inhibitable cytochrome c reduction, and superoxide
      production remained elevated for up to 60 min of exposure. To measure gap
      junction communication, Lucifer yellow dye was injected into myometrial cells,
      and dye transfer to adjoining cells was monitored. Cells were exposed to lindane
      with or without GSH modulators, and dye transfer was determined at the end of a 1
      h exposure to 100 microM lindane (acute phase) and 24 h after termination of
      lindane exposure (secondary phase). The acute phase of lindane-induced inhibition
      of dye transfer was prevented by GSH depletion with L-buthionine-[S,R]
      sulfoximine (BSO) and enhanced by GSH augmentation with GSH monoethyl ester or L
      2-oxothiazolidine-4-carboxylate (OTC). In contrast, the secondary, delayed-onset
      phase of lindane-induced inhibition of dye transfer was enhanced by GSH depletion
      with BSO and prevented by GSH augmentation with GSH monoethyl ester or OTC.
      Changes in cellular GSH by the pharmacological modulators were confirmed by high
      performance liquid chromatography. These results suggest that GSH is required in
      the acute phase but protects against the secondary phase of lindane-induced
      inhibition of myometrial gap junctions.

PMID- 15716480
TI  - Mechanisms of exocrine pancreatic toxicity induced by oral treatment with 2,3,7,8
      tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley Rats.
AB  - In previous 2-year studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      conducted by the National Toxicology Program on female Harlan Sprague-Dawley
      rats, acinar-cell vacuolation, atrophy, inflammation, and arteritis developed at
      high incidence, and a rare occurrence of pancreatic acinar-cell adenomas and
      carcinomas was noted. In this investigation, we sought to identify the mechanism
      involved in the early formative stages of acinar-cell lesions. Pancreas from
      animals treated for 14 and 31 weeks with 100 ng TCDD/kg body weight or corn oil
      vehicle was examined immunohistochemically and/or morphometrically. Acinar-cell
      kinetics were analyzed using staining with hematoxylin and eosin and
      proliferating cell nuclear antigen. Expressions of cytochrome P450 (CYP) 1A1 and
      aryl hydrocarbon receptor (AhR) were evaluated to assess direct effects of TCDD
      exposure. The cholecystokinin-A receptor (CCK-A receptor; CCKAR) and duodenal
      cholecystokinin 8 (CCK) revealed the associations of dioxin treatment with
      hormonal changes. Amylase localization showed acinar structural changes that
      could affect enzymatic production. Increased apoptotic activity in acinar cells
      occurred in 14- and 31-week-treated animals, with an increase in proliferative
      activity in the latter. Also in the latter, in the vacuolated acinar cells,
      CYP1A1 was overexpressed, and statistically significant decreases in expressions
      of AhR, CCKAR, and amylase occurred. The intensity of CCKAR expression increased
      in nonvacuolated acinar cells; a decrease in the size of CCK-positive epithelial
      cells occurred in duodenum. Our findings indicate that dioxin-induced acinar-cell
      lesions might be related to a direct effect of TCDD on the pancreas. Increase in
      CYP1A1 and decrease in CCKAR expressions in vacuolated acinar cells may be
      involved in the pathogenesis of pancreatic lesions. Changes in the expression of
      CYP or CCKAR may have induced the acinar-cell tumors by initiating proliferation.

PMID- 15716479
TI  - Disruption of thyroid hormone homeostasis at weaning of Holtzman rats by
      lactational but not in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - The purpose of this study is to clarify whether lactational exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) is entirely responsible for the perturbation
      in thyroid hormone homeostasis during the neonatal period. Pregnant Holtzman rats
      were given a single oral dose of 1.0 mug TCDD/kg body weight on gestational day
      15. Half of the litters were cross-fostered with the half of the dams treated
      with vehicle on postnatal day (PND) 1 to make four groups of rats, control (C/C),
      prenatal TCDD exposure only (T/C), postnatal TCDD exposure only (C/T), and both
      prenatal and postnatal TCDD exposure (T/T). On PND 21, the C/T and T/T groups,
      but not the T/C and C/C groups, showed a significant decrease in serum total
      thyroxin (TT4) and free thyroxin (FT4) concentrations in both sexes and a
      significant increase in serum thyroid-stimulating hormone (TSH) levels,
      particularly male pups. These two groups of male and female pups had
      significantly higher concentrations of TCDD in the liver, with marked induction
      of cytochrome P450 (CYP) 1A1 mRNA and intense immunostaining of CYP1A1 in the
      liver. UDP glycosyltransferase 1 family, polypeptide A6 (UGT1A6) and UGT1A7 mRNAs
      were induced in their livers, with marked immunostaining of UGT1A6. The transfer
      of TCDD from dams to the pups was confirmed by the detection of TCDD in mother's
      milk remaining in the stomachs of lactationally exposed pups on PND 1. The
      present results demonstrate that lactational, but not in utero, exposure to TCDD
      was responsible for the disruption of thyroid hormone homeostasis.

PMID- 15716481
TI  - Incorporation of therapeutic interventions in physiologically based
      pharmacokinetic modeling of human clinical case reports of accidental or
      intentional overdosing with ethylene glycol.
AB  - Although occupational uses of the high production volume (HPV) chemical ethylene
      glycol (EG) have not been associated with adverse effects, there are case reports
      where humans have either intentionally or accidentally ingested large quantities
      of EG, primarily from antifreeze. The acute toxicity of EG can proceed through
      three stages, each associated with a different metabolite: central nervous system
      depression (ethylene glycol), cardiopulmonary effects associated with metabolic
      acidosis (glycolic acid), and ultimately renal toxicity (oxalic acid), depending
      on the total amounts consumed and the effectiveness of therapeutic interventions.
      A physiologically based pharmacokinetic (PBPK) model developed in a companion
      paper (Corley et al., 2005). Development of a physiologically based
      pharmacokinetic model for ethylene glycol and its metabolite, glycolic acid, in
      rats and humans. Toxicol. Sci., in press 2005) was refined in this study to
      include clinically relevant treatment regimens for EG poisoning such as
      hemodialysis or metabolic inhibition with either ethanol or fomepizole. Such
      modifications enabled the model to describe data from several human case reports,
      confirming the ability of the previous model to describe the pharmacokinetics of
      EG and its metabolite, glycolic acid, in humans across a broad range of doses and
      multiple exposure routes. By integrating the case report data sets with
      controlled studies in this PBPK model, it was demonstrated that fomepizole, if
      administered early enough in a clinical situation, can be more effective than
      ethanol or hemodialysis in preventing the metabolism of EG to more toxic
      metabolites. Hemodialysis remains an important option, however, if treatment is
      instituted after a significant amount of EG is metabolized or if renal toxicity
      has occurred.

PMID- 15716482
TI  - Development of a physiologically based pharmacokinetic model for ethylene glycol
      and its metabolite, glycolic Acid, in rats and humans.
AB  - An extensive database on the toxicity and modes of action of ethylene glycol (EG)
      has been developed over the past several decades. Although renal toxicity has
      long been recognized as a potential outcome, in recent years developmental
      toxicity, an effect observed only in rats and mice, has become the subject of
      extensive research and regulatory reviews to establish guidelines for human
      exposures. The developmental toxicity of EG has been attributed to the
      intermediate metabolite, glycolic acid (GA), which can become a major metabolite
      when EG is administered to rats and mice at high doses and dose rates. Therefore,
      a physiologically based pharmacokinetic (PBPK) model was developed to integrate
      the extensive mode of action and pharmacokinetic data on EG and GA for use in
      developmental risk assessments. The resulting PBPK model includes inhalation,
      oral, dermal, intravenous, and subcutaneous routes of administration. Metabolism
      of EG and GA were described in the liver with elimination via the kidneys.
      Metabolic rate constants and partition coefficients for EG and GA were estimated
      from in vitro studies. Other biochemical constants were optimized from
      appropriate in vivo pharmacokinetic studies. Several controlled rat and human
      metabolism studies were used to validate the resulting PBPK model. When internal
      dose surrogates were compared in rats and humans over a broad range of exposures,
      it was concluded that humans are unlikely to achieve blood levels of GA that have
      been associated with developmental toxicity in rats following occupational or
      environmental exposures.

PMID- 15716483
TI  - Evaluation of polycyclic aromatic hydrocarbons in the activation of early growth
      response-1 and peroxisome proliferator activated receptors.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental and food
      contaminants with known or suspected carcinogenic properties. In this study, we
      have evaluated whether PAHs activate the early growth response (EGR-1) gene and
      bind to peroxisome proliferator-activated receptor alpha (PPAR alpha) and delta
      (PPAR beta/delta) in cell culture systems. Luciferase reporter systems were
      employed and several PAHs were evaluated for their ability to activate EGR-1 and
      PPARs. Some PAHs enhanced EGR-1 expression and activated PPAR alpha and PPAR
      beta. Among them, benz(a)anthracene was found to act as a relatively potent
      activator of PPAR alpha and PPAR beta/delta, and to significantly enhance EGR-1
      transcription. These in vitro assays were confirmed by Western blot analysis,
      using cell lysates of tissue samples from mouse trapped at a highly contaminated
      Superfund site in the Chattanooga Creek floodplain in Chattanooga, Tennessee. We
      have found that a PPAR target gene, glycogen synthase kinase-3beta (GSK-3beta),
      was down-regulated and EGR-1 was up-regulated in the mouse samples of Chattanooga
      Creek. In addition, select PAHs repressed GSK-3beta and induced CYP4A in FaO rat
      hepatoma cells. In conclusion, PAHs activate PPAR alpha and PPAR beta/delta, and
      up-regulate EGR-1 expression in vitro as well as in vivo. These data may provide
      a diversity of PAH activity in several biological pathways.

PMID- 15716484
TI  - Cisplatin-induced apoptosis is enhanced by hypoxia and by inhibition of
      mitochondria in renal collecting duct cells.
AB  - Cisplatin is a widely used chemotherapeutic agent. Here we show that cisplatin
      induces apoptosis in renal collecting duct-derived cells (MDCK-C7 cells,
      resembling principal cells) in a dose-dependent manner. Additionally, we studied
      the role of mitochondria in this process by inhibition of the mitochondrial
      respiratory chain, the F1F(o)-ATP synthase or by uncoupling. The role of intra-
      and extracellular pH in apoptosis induction was investigated. Activation of
      caspase-3 and DNA ladder formation were used to monitor the apoptotic response.
      When cells were incubated with inhibitors of the mitochondrial respiratory chain
      or an inhibitor of the ATP-synthase, cisplatin-induced apoptosis was markedly
      enhanced. Mitochondrial blockade led to enhanced production of lactic acid. Also,
      anoxia potentiated the cisplatin-induced caspase-3 activation. Neither intra- nor
      extracellular pH had an influence on caspase-3 activation at low cisplatin
      concentrations. Acidic conditions (pH 6.8) potentiated the caspase-3 activation
      when high (100 microM) cisplatin concentrations were used. We demonstrate that
      intact mitochondria are important to prevent cisplatin-induced apoptosis in MDCK
      C7 cells and that acidic conditions can aggravate the toxic effects of cisplatin.

PMID- 15716485
TI  - Cardiovascular gene expression profiles of dioxin exposure in zebrafish embryos.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental
      contaminant that causes altered heart morphology, circulatory impairment, edema,
      hemorrhage, and early life stage mortality in fish. TCDD toxicity is dependent,
      in large part, on the aryl hydrocarbon receptor (AHR), but understanding of the
      molecular mechanism of cardiovascular embryotoxicity remains incomplete. To
      identify genes potentially involved in cardiovascular effects, we constructed
      custom cDNA microarrays consisting of 4896 zebrafish adult heart cDNA clones and
      over 200 genes with known developmental, toxicological and housekeeping roles.
      Gene expression profiles were obtained for 3-day-old zebrafish after early
      embryonic exposure to either 0.5 or 5.0 nM TCDD. In all, 516 clones were
      significantly differentially expressed (p < 0.005) under at least one treatment
      condition; 123 high-priority clones were selected for further investigation.
      Cytochromes P450 1A and 1B1, and other members of the AHR gene battery, were
      strongly and dose-dependently induced by TCDD. Importantly, altered expression of
      cardiac sarcomere components, including cardiac troponin T2 and multiple myosin
      isoforms, was consistent with the hypothesis that TCDD causes dilated
      cardiomyopathy. Observed increases in expression levels of mitochondrial energy
      transfer genes also may be related to cardiomyopathy. Other TCDD-responsive genes
      included fatty acid and steroid metabolism enzymes, ribosomal and signal
      transduction proteins, and 18 expressed sequence tags (ESTs) with no known
      protein homologs. As the first broad-scale study of TCDD-modulated gene
      expression in a non-mammalian system, this work provides an important perspective
      on mechanisms of TCDD toxicity.

PMID- 15716486
TI  - Variability in human sensitivity to 1,3-butadiene: influence of polymorphisms in
      the 5'-flanking region of the microsomal epoxide hydrolase gene (EPHX1).
AB  - The carcinogenic effects of 1,3-butadiene (BD), a mutagenic chemical widely used
      in the manufacture of synthetic rubber, are likely initiated through its epoxide
      metabolites. In humans, these epoxides are detoxified predominantly by
      hydrolysis, a reaction mediated by the microsomal epoxide hydrolase (mEH; EPHX1)
      enzyme. It appears reasonable to hypothesize that BD-exposed individuals
      possessing lower mEH detoxification capacity may have elevated risk of adverse
      health effects. The interindividual levels of mEH enzymatic activity vary
      considerably, and polymorphisms in the mEH gene may contribute to this
      variability. In addition to the well-studied coding region polymorphisms encoding
      Tyr113His and His139Arg substitutions, seven other polymorphic sites in the 5'
      flanking region of the mEH gene have been reported. These polymorphisms appear to
      differentially affect mEH gene transcriptional activities. The 5'-flanking region
      polymorphisms exist in two linkages, the -200 linkage (-200C/T, -259C/T, -290T/G)
      and the -600 linkage (-362A/G, -613T/C, -699T/C), whereas the -399T/C
      polymorphism exists as an independent site. Because these polymorphisms may
      affect total mEH enzymatic activity, we hypothesized that they influence the
      mutagenic response associated with occupational exposure to BD. We genotyped the
      5'-region of the mEH gene in 49 non-smoking workers from two styrene-butadiene
      rubber facilities in southeast Texas and evaluated the linkage patterns against
      results obtained from an autoradiographic HPRT mutant lymphocyte assay, used as a
      biomarker of genotoxic effect. In the study population, 67% were exposed to low
      BD levels, <150 parts per billion, and 33% were exposed to >150 ppb. We used the
      observed HPRT mutant (variant) frequency (VF) in the studied population and a 4
      way first-order interaction statistical model to estimate parameters that
      describe the influence of exposure, genotypes and the interaction between the two
      on the HPRT VF in the target population. The background (baseline) VF, defined as
      the VF (x 10(-6)) +/- S.E.M. at low levels of BD exposure (<150 ppb) where all
      the genotypes under study are homozygous wild-type, was estimated to be 4.02 +/-
      1.32. Exposure to >150 ppb of BD alone resulted in an estimated increase in VF of
      3.42 +/- 2.47 above the baseline level. Inheritance of the variant ATT allele in
      the -600 linkages resulted in an estimated increase in VF of 3.39 +/- 1.67 above
      the baseline level. When the interaction between BD exposure and the ATT allele
      in the -600 linkage group was considered, a statistically significant positive
      interaction was observed, with an estimated increase in the VF of 10.89 +/- 2.16
      (95% CI = 6.56-15.20; p = 0.0027) above baseline. These new data confirm and
      extend our previous findings that sensitivity to the genotoxic effects of BD is
      inversely correlated with predicted mEH activity.

PMID- 15716487
TI  - Selenium compounds prevent the effects of methylmercury on the in vitro
      phosphorylation of cytoskeletal proteins in cerebral cortex of young rats.
AB  - In this study we investigated the protective ability of the selenium compounds
      ebselen and diphenyldiselenide against the effect of methylmercury on the in
      vitro incorporation of 32P into intermediate filament (IF) proteins from the
      cerebral cortex of 17-day-old rats. We observed that methylmercury in the
      concentrations of 1 and 5 microM was able to inhibit the phosphorylating system
      associated with IF proteins without altering the immunocontent of these proteins.
      Concerning the selenium compounds, diselenide (1, 15, and 50 microM) did not
      induce alteration of the in vitro phosphorylation of IF proteins. Conversely, 15
      microM diselenide was effective in preventing the toxic effects induced by
      methylmercury. Otherwise, ebselen induced an altered in vitro phosphorylation of
      the cytoskeletal proteins in a dose-dependent manner. Ebselen at intermediate
      concentrations (15 and 30 microM) increased the in vitro phosphorylation.
      However, at low (5 microM) or high (50 and 100 microM) concentrations it was
      ineffective in altering the cytoskeletal-associated phosphorylating system.
      Furthermore, 5 microM ebselen presented a protective effect against the action of
      methylmercury on the phosphorylating system. In conclusion, our results indicate
      that the selenium compounds ebselen and diselenide present protective actions
      toward the alterations of the phosphorylating system associated with the IF
      proteins induced by methylmercury in slices of the cerebral cortex of rats.

PMID- 15716488
TI  - Enhancement by estradiol 3-benzoate in thioacetamide-induced liver cirrhosis of
      rats.
AB  - As part of an investigation on the role of estrogen in liver disease, we tested
      the effects of estradiol-3-benzoate (EB) in the thioacetamide (TAA)-induced rat
      liver cirrhosis model. Male F344 rats (n = 100) were divided into six groups.
      Animals of groups 1-4 received TAA (0.03% in drinking water) for 12 weeks, and
      groups 5 and 6 served as controls without TAA. For the exposure period, EB
      pellets were implanted subcutaneously to give doses of 0 (groups 1 and 5), 1
      (group 2), 10 (group 3), and 100 mug (groups 4 and 6) simultaneously. All animals
      were sacrificed at week 12. Significant increase of liver cirrhosis, liver
      weight, collagen content, and lipid peroxidation in the livers was evident in
      groups 3 and 4 (p < 0.05) compared with group 1. Formation of 8-hydroxy-2'
      deoxyguanosine (8-OHdG) was significantly elevated in group 4 (p < 0.01), along
      with expression of alpha-smooth muscle actin (alpha-SMA) and stellate cell
      activation-associated protein (STAP), as determined by RT-PCR analysis (p <
      0.01). However, there were no differences in liver weight, collagen content,
      lipid peroxidation, 8-OHdG formation, and alpha-SMA and STAP mRNA expression
      between groups 5 and 6. We conclude that EB treatment enhances TAA-induced
      cirrhosis, associated with increase of oxidative stress and activation of hepatic
      stellate cells.

PMID- 15716489
TI  - Phenols, quinolines, indoles, benzene, and 2-cyclopenten-1-ones are oviductal
      toxicants in cigarette smoke.
AB  - Previously, we showed that pyridines and pyrazines in cigarette smoke inhibit
      oviductal functioning in vitro in nanomolar and picomolar doses. The purpose of
      this study was to determine the lowest observable adverse effect levels (LOAELs)
      of phenols, quinolines, indoles, benzene, and 2-cyclopenten-1-ones found in
      mainstream smoke solutions on ciliary beat frequency, oocyte pickup rate, and
      infundibular smooth muscle contraction using the hamster oviduct. After solid
      phase extraction, mainstream smoke solution fractions were tested in the
      oviductal assays. The active fractions were analyzed using gas chromatography
      mass spectrometry to identify individual chemicals. Using this approach, benzene,
      eleven phenolic, two indole, two quinoline, and two 2-cyclopenten-1-one
      derivatives were identified in the active fractions. Commercially available
      authentic standards of the identified compounds were tested in dose-response
      studies on hamster oviducts. The LOAELs were determined for each compound using
      the ciliary beat frequency, oocyte pickup rate, and infundibular smooth muscle
      contraction rate assays. Indole, the compound with the highest potency, showed
      inhibition of ciliary beat frequency (10(-13) M), oocyte pickup rate (10(-14) M),
      and infundibular smooth muscle contraction rate (10(-15) M) in femtomolar doses.
      All of the other compounds tested, except phenol, which only showed inhibition at
      millimolar concentrations, were inhibitory in picomolar, nanomolar, or micromolar
      concentrations. Derivitization of phenol increased its toxicity in the oviductal
      assays, especially when a methyl or ethyl group was substituted on the fourth
      position. The indoles, quinolines, and four phenolic compounds had both high
      potencies and efficacies in the oviductal assays.

PMID- 15716490
TI  - Drosophila signal peptide peptidase is an essential protease for larval
      development.
AB  - We identified the Drosophila melanogaster Signal peptide peptidase gene (Spp)
      that encodes a multipass transmembrane aspartyl protease. Drosophila SPP is
      homologous to the human signal peptide peptidase (SPP) and is distantly related
      to the presenilins. We show that, like human SPP, Drosophila SPP can proteolyze a
      model signal peptide and is sensitive to an SPP protease inhibitor and that it
      localizes to the endoplasmic reticulum. Expression of Drosophila SPP was first
      apparent at germ band extension, and in late embryos it was robust in the
      salivary glands, proventriculus, and tracheae. Flies bearing mutations in
      conserved residues or carrying deficiencies for the Spp gene had defective
      tracheae and died as larvae.

PMID- 15716492
TI  - Optimizing the nucleotide sequence of a meiotic recombination hotspot in
      Schizosaccharomyces pombe.
AB  - The ade6-M26 mutation of Schizosaccharomyces pombe created a meiotic
      recombination hotspot. Previous analyses indicated that the heptamer 5'-ATGACGT
      3' was necessary and sufficient for hotspot activity; the Atf1-Pcr1 transcription
      factor binds to this sequence and activates M26. After finding cases in which the
      M26 heptamer in ade6 was, surprisingly, not active as a hotspot, we used an in
      vitro selection method (SELEX) that revealed an 18-bp consensus sequence for Atf1
      Pcr1 binding, 5'-GNVTATGACGTCATNBNC-3', containing the M26 heptamer at its core.
      Using this consensus sequence as a guide, we made mutations on each side of the
      heptamer at two separate sites in ade6. These mutations increased the
      intracellular hotspot activity of the heptamer, in some cases by >15-fold. These
      results show that M26, the eukaryotic recombination hotspot with the most
      precisely defined nucleotide sequence, is larger than previously thought, and
      they provide valuable information for clarifying the role of M26, and perhaps
      other hotspots, in meiotic recombination.

PMID- 15716493
TI  - Mutation rates, spectra and hotspots in mismatch repair-deficient Caenorhabditis
      elegans.
AB  - Although it is clear that postreplicative DNA mismatch repair (MMR) plays a
      critical role in maintaining genomic stability in nearly all forms of life
      surveyed, much remains to be understood about the genome-wide impact of MMR on
      spontaneous mutation processes and the extent to which MMR-deficient mutation
      patterns vary among species. We analyzed spontaneous mutation processes across
      multiple genomic regions using two sets of mismatch repair-deficient (msh-2 and
      msh-6) Caenorhabditis elegans mutation-accumulation (MA) lines and compared our
      observations to mutation spectra in a set of wild-type (WT), repair-proficient C.
      elegans MA lines. Across most sequences surveyed in the MMR-deficient MA lines,
      mutation rates were approximately 100-fold higher than rates in the WT MA lines,
      although homopolymeric nucleotide-run (HP) loci composed of A:T base pairs
      mutated at an approximately 500-fold greater rate. In contrast to yeast and
      humans where mutation spectra vary substantially with respect to different
      specific MMR-deficient genotypes, mutation rates and patterns were overall highly
      similar between the msh-2 and msh-6 C. elegans MA lines. This, along with the
      apparent absence of a Saccharomyces cerevisiae MSH3 ortholog in the C. elegans
      genome, suggests that C. elegans MMR surveillance is carried out by a single Msh
      2/Msh-6 heterodimer.

PMID- 15716491
TI  - Identification of zebrafish insertional mutants with defects in visual system
      development and function.
AB  - Genetic analysis in zebrafish has been instrumental in identifying genes
      necessary for visual system development and function. Recently, a large-scale
      retroviral insertional mutagenesis screen, in which 315 different genes were
      mutated, that resulted in obvious phenotypic defects by 5 days postfertilization
      was completed. That the disrupted gene has been identified in each of these
      mutants provides unique resource through which the formation, function, or
      physiology of individual organ systems can be studied. To that end, a screen for
      visual system mutants was performed on 250 of the mutants in this collection,
      examining each of them histologically for morphological defects in the eye and
      behaviorally for overall visual system function. Forty loci whose disruption
      resulted in defects in eye development and/or visual function were identified.
      The mutants have been divided into the following phenotypic classes that show
      defects in: (1) morphogenesis, (2) growth and central retinal development, (3)
      the peripheral marginal zone, (4) retinal lamination, (5) the photoreceptor cell
      layer, (6) the retinal pigment epithelium, (7) the lens, (8) retinal containment,
      and (9) behavior. The affected genes in these mutants highlight a diverse set of
      proteins necessary for the development, maintenance, and function of the
      vertebrate visual system.

PMID- 15716494
TI  - Linkage disequilibrium grouping of single nucleotide polymorphisms (SNPs)
      reflecting haplotype phylogeny for efficient selection of tag SNPs.
AB  - Single nucleotide polymorphisms (SNPs) have been proposed to be grouped into
      haplotype blocks harboring a limited number of haplotypes. Within each block, the
      portion of haplotypes is expected to be tagged by a selected subset of SNPs;
      however, none of the proposed selection algorithms have been definitive. To
      address this issue, we developed a tag SNP selection algorithm based on grouping
      of SNPs by the linkage disequilibrium (LD) coefficient r(2) and examined five
      genes in three ethnic populations--the Japanese, African Americans, and
      Caucasians. Additionally, we investigated ethnic diversity by characterizing 979
      SNPs distributed throughout the genome. Our algorithm could spare 60% of SNPs
      required for genotyping and limit the imprecision in allele-frequency estimation
      of nontag SNPs to 2% on average. We discovered the presence of a mosaic pattern
      of LD plots within a conventionally inferred haplotype block. This emerged
      because multiple groups of SNPs with strong intragroup LD were mingled in their
      physical positions. The pattern of LD plots showed some similarity, but the
      details of tag SNPs were not entirely concordant among three populations.
      Consequently, our algorithm utilizing LD grouping allows selection of a more
      faithful set of tag SNPs than do previous algorithms utilizing haplotype blocks.

PMID- 15716496
TI  - Isolation and characterization of novel xrs2 mutations in Saccharomyces
      cerevisiae.
AB  - The Mre11/Rad50/Xrs2 (MRX) complex is involved in DNA damage repair, DNA damage
      response, telomere control, and meiotic recombination. Here, we constructed and
      characterized novel mutant alleles of XRS2. The alleles with mutations in the C
      terminal conserved domain of Xrs2 were grouped into the same class. Mutant Xrs2
      in this class lacked Mre11 interaction ability. The second class, lacking a C
      terminal end, showed defects only in telomere control. A previous study showed
      that this C-terminal end contains a Tel1-association domain. These results
      indicate that Xrs2 contains two functional domains, Mre11- and Tel1-binding
      domains. While the Mre11-binding domain is essential for Xrs2 function, the Tel1
      binding domain may be essential only for Tel1 function in telomere maintenance.
      The third class, despite containing a large deletion in the N-terminal region,
      showed no defects in DNA damage repair. However, some mutants, which showed a
      reduced level of Xrs2 protein, were partially defective in formation of meiotic
      DSBs and telomere maintenance. These defects were suppressed by overexpression of
      the mutant Xrs2 protein. This result suggests that the total amount of Xrs2
      protein is a critical determinant for the function of the MRX complex especially
      with regard to telomere maintenance and meiotic DSB formation.

PMID- 15716495
TI  - The Snf1 protein kinase and Sit4 protein phosphatase have opposing functions in
      regulating TATA-binding protein association with the Saccharomyces cerevisiae
      INO1 promoter.
AB  - To identify the mechanisms by which multiple signaling pathways coordinately
      affect gene expression, we investigated regulation of the S. cerevisiae INO1
      gene. Full activation of INO1 transcription occurs in the absence of inositol and
      requires the Snf1 protein kinase in addition to other signaling molecules and
      transcription factors. Here, we present evidence that the Sit4 protein
      phosphatase negatively regulates INO1 transcription. A mutation in SIT4 was
      uncovered as a suppressor of the inositol auxotrophy of snf1Delta strains. We
      found that sit4 mutant strains exhibit an Spt(-) phenotype, suggesting a more
      general role for Sit4 in transcription. In fact, like the gene-specific
      regulators of INO1 transcription, Opi1, Ino2, and Ino4, both Snf1 and Sit4
      regulate binding of TBP to the INO1 promoter, as determined by chromatin
      immunoprecipitation analysis. Experiments involving double-mutant strains
      indicate that the negative effect of Sit4 on INO1 transcription is unlikely to
      occur through dephosphorylation of histone H3 or Opi1. Sit4 is a known component
      of the target of rapamycin (TOR) signaling pathway, and treatment of cells with
      rapamycin reduces INO1 activation. However, analysis of rapamycin-treated cells
      suggests that Sit4 represses INO1 transcription through multiple mechanisms, only
      one of which may involve inhibition of TOR signaling.

PMID- 15716497
TI  - Requirements for replication restart proteins during constitutive stable DNA
      replication in Escherichia coli K-12.
AB  - Constitutive stable DNA replication (cSDR) is a mechanism for replisome loading
      in Escherichia coli K-12. This occurs in a dnaA-independent fashion in an rnhA
      mutant. cSDR is dependent on recA, priA, and transcription. In this report, it is
      shown that dnaA rnhA mutants using cSDR for initiation of their DNA replication
      additionally require priB, but not priC, for viability. Two subtle priA missense
      mutations either eliminated the ability to grow using cSDR (priA301 C479Y) or
      resulted in very small colonies (priA300 K230R). DnaC809, a priA suppressor,
      failed to allow priA or priB mutants to grow using cSDR to initiate DNA
      replication. Furthermore, unlike dnaC(+) strains, dnaC809 strains require priC
      for cSDR. DnaC809,820, a priC-independent suppressor of priA2::kan phenotypes,
      allowed priA and priC (but not priB) mutants to grow using cSDR to initiate DNA
      replication. It is also shown that rep and rnhA mutations are synthetically
      lethal. DnaC809 and dnaC809,820 mutations suppress this lethality. Rep is further
      shown to be required for cSDR in a dnaC809 strain. A model whereby these
      different sets of replication restart proteins interact preferentially with
      substrates associated with either RecA or SSB during replication restart and
      cSDR, respectively, is proposed.

PMID- 15716498
TI  - Soft sweeps: molecular population genetics of adaptation from standing genetic
      variation.
AB  - A population can adapt to a rapid environmental change or habitat expansion in
      two ways. It may adapt either through new beneficial mutations that subsequently
      sweep through the population or by using alleles from the standing genetic
      variation. We use diffusion theory to calculate the probabilities for selective
      adaptations and find a large increase in the fixation probability for weak
      substitutions, if alleles originate from the standing genetic variation. We then
      determine the parameter regions where each scenario-standing variation vs. new
      mutations-is more likely. Adaptations from the standing genetic variation are
      favored if either the selective advantage is weak or the selection coefficient
      and the mutation rate are both high. Finally, we analyze the probability of "soft
      sweeps," where multiple copies of the selected allele contribute to a
      substitution, and discuss the consequences for the footprint of selection on
      linked neutral variation. We find that soft sweeps with weaker selective
      footprints are likely under both scenarios if the mutation rate and/or the
      selection coefficient is high.

PMID- 15716499
TI  - Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast.
AB  - Haploinsufficiency is defined as a dominant phenotype in diploid organisms that
      are heterozygous for a loss-of-function allele. Despite its relevance to human
      disease, neither the extent of haploinsufficiency nor its precise molecular
      mechanisms are well understood. We used the complete set of Saccharomyces
      cerevisiae heterozygous deletion strains to survey the genome for
      haploinsufficiency via fitness profiling in rich (YPD) and minimal media to
      identify all genes that confer a haploinsufficient growth defect. This assay
      revealed that approximately 3% of all approximately 5900 genes tested are
      haploinsufficient for growth in YPD. This class of genes is functionally enriched
      for metabolic processes carried out by molecular complexes such as the ribosome.
      Much of the haploinsufficiency in YPD is alleviated by slowing the growth rate of
      each strain in minimal media, suggesting that certain gene products are rate
      limiting for growth only in YPD. Overall, our results suggest that the primary
      mechanism of haploinsufficiency in yeast is due to insufficient protein
      production. We discuss the relevance of our findings in yeast to human
      haploinsufficiency disorders.

PMID- 15716500
TI  - Slit-roundabout signaling neutralizes netrin-Frazzled-mediated attractant cue to
      specify the lateral positioning of longitudinal axon pathways.
AB  - An extending axon growth cone is subjected to attractant and repellent cues. It
      is not clear how these growth cones discriminate the two opposing forces and
      select their projection paths. Here, we report that in the Drosophila nerve cord
      the growth cones of longitudinal tracts are subjected to attraction by the Netrin
      Frazzled pathway. However, the midline Slit neutralizes this pathway in a Robo
      dependent manner and prevents Netrin-Frazzled-mediated attraction of longitudinal
      tracts. Our results suggest that the loss of a neutralizing effect on the Netrin
      mediated attraction is responsible for the longitudinal tracts entering the
      midline in slit mutants as opposed to a loss of repulsion as is currently
      believed. This effect is not via a direct inhibition of Frazzled by Robo;
      instead, it is at a level downstream of Frazzled. Thus, the growth cones of
      longitudinal tracts subjected to two opposing forces are able to block one with
      the other and specify their correct lateral positioning along the midline.

PMID- 15716501
TI  - Mutation rate variation at human dinucleotide microsatellites.
AB  - Mutation is the ultimate source of genetic variation, and mutation rate is thus
      an important parameter governing the extent of genetic variation. Microsatellites
      are highly informative genetic markers that have been widely used in genetic
      studies. While previous studies showed that the mutation rate differs in di-, tri
      , and tetranucleotide repeats, how mutation rate distributes within each class of
      repeat is poorly understood. This study first revealed the pattern of the
      mutation rate variation within the dinucleotide repeats. Two data sets were used.
      The first is the allele frequency data from 115 microsatellites with dinucleotide
      repeats distributed along the human genome in 10 worldwide populations. The
      second data set is much larger, consisting of the allele frequency of 5252
      dinucleotide repeats from the Genome Database. Mutation rate for each locus is
      estimated through a new homozygosity-based estimator, which has been shown to be
      unbiased and highly efficient and is reasonably robust against deviations from
      the single-step model. The mutation rates among loci can be approximated well by
      a gamma distribution and its shape parameter can be accurately estimated with
      this approach. This result provides the basic guidelines for analyzing the large
      scale genomic data from microsatellite loci.

PMID- 15716502
TI  - The zebrafish pob gene encodes a novel protein required for survival of red cone
      photoreceptor cells.
AB  - The zebrafish mutant, partial optokinetic response b (pob), was isolated using an
      N-ethyl N-nitrosourea (ENU)-based screening strategy designed to identify larvae
      with defective optokinetic responses in red but not white light. Previous studies
      showed that red-light blindness in pob is due to the specific loss of long
      wavelength photoreceptor cells via an apoptotic mechanism. Here, we used
      positional cloning to identify the mutated pob gene. We find that pob encodes a
      highly conserved 30-kDa protein of unknown function. To demonstrate that the
      correct gene was isolated, we used the Tol2 transposon system to generate
      transgenic animals and rescue the mutant phenotype. The Pob protein contains
      putative transmembrane regions and protein-sorting signals. It is localized to
      the inner segment and synapse in photoreceptor cells, and when expressed in COS-7
      cells it localizes to intracellular compartments. We also show that the
      degeneration of red cone photoreceptors in the mutants occurs independently of
      light. On the basis of our findings, we propose that Pob is not involved in
      phototransduction but rather plays an essential role in protein sorting and/or
      trafficking.

PMID- 15716503
TI  - Identification and characterization of regions of the rice genome associated with
      broad-spectrum, quantitative disease resistance.
AB  - Much research has been devoted to understanding the biology of plant-pathogen
      interactions. The extensive genetic analysis of disease resistance in rice,
      coupled with the sequenced genome and genomic resources, provides the opportunity
      to seek convergent evidence implicating specific chromosomal segments and genes
      in the control of resistance. Published data on quantitative and qualitative
      disease resistance in rice were synthesized to evaluate the distributions of and
      associations among resistance loci. Quantitative trait loci (QTL) for resistance
      to multiple diseases and qualitative resistance loci (R genes) were clustered in
      the rice genome. R genes and their analogs of the nucleotide binding site-leucine
      rich repeat class and genes identified on the basis of differential
      representation in disease-related EST libraries were significantly associated
      with QTL. Chromosomal segments associated with broad-spectrum quantitative
      disease resistance (BS-QDR) were identified. These segments contained numerous
      positional candidate genes identified on the basis of a range of criteria, and
      groups of genes belonging to two defense-associated biochemical pathways were
      found to underlie one BS-QDR region. Genetic dissection of disease QTL confidence
      intervals is needed to reduce the number of positional candidate genes for
      further functional analysis. This study provides a framework for future
      investigations of disease resistance in rice and related crop species.

PMID- 15716504
TI  - Eae19, a new locus on rat chromosome 15 regulating experimental autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis (MS) and its animal model, myelin oligodendrocyte glycoprotein
      induced experimental autoimmune encephalomyelitis (MOG-EAE), share a complex
      genetic predisposition with contributions from the major histocompatibility
      complex class II genes and many other genes. Linkage mapping in F(2) crosses
      between the susceptible DA rat strain and the resistant ACI or BN rat strains in
      various models of autoimmune neuroinflammation have repeatedly displayed
      suggestive linkage to a region on rat chromosome 15. A direct study of this
      region was undertaken in congenic strains by transferring resistant ACI alleles
      to the susceptible DA background. Phenotypic analysis demonstrated lower maximal
      and cumulative EAE scores in the DA.ACI-D15Rat6-D15Rat71 (C15), DA.ACI-D15Rat6
      D15Rat48, D15Rat126-D15Rat71 (C15R3b), and DA.ACI-D15Rat23-D15rat71 (C15R4)
      strains compared to the parental DA rat strain. Linkage analysis was then
      performed in a (DA x PVG.AV1)F(7) advanced intercross line, resulting in a LOD
      score of 4.7 for the maximal EAE score phenotype at the peak marker D15Rat71 and
      a confidence interval of 13 Mb, overlapping with the congenic fragment defined by
      the C15R3b and the C15R4 strains. Thus, a new MOG-EAE locus with the designation
      Eae19 is identified on rat chromosome 15. There are 32 confirmed or predicted
      genes in the confidence interval, including immune-responsive gene 1 and neuronal
      ceroid lipofuscinose gene 5. Definition of loci such as Eae19 enables the
      characterization of genetically regulated, evolutionary conserved disease
      pathways in complex neuroinflammatory diseases.

PMID- 15716505
TI  - A second-generation genetic linkage map of tilapia (Oreochromis spp.).
AB  - We constructed a second-generation linkage map of tilapia from the F(2) progeny
      of an interspecific cross between Oreochromis niloticus and Oreochromis aureus.
      The map reported here contains 525 microsatellite and 21 gene-based markers. It
      spans 1311 cM in 24 linkage groups, for an average marker spacing of 2.4 cM. We
      detected associations of sex and red color with markers on linkage group 3. This
      map will enable mapping and selective breeding of quantitative traits important
      to the economic culture of tilapia as a food fish and will contribute to the
      study of closely related cichlids that have undergone explosive adaptive
      radiation in the lakes of East Africa.

PMID- 15716507
TI  - Elevated polymorphism and divergence in the class C scavenger receptors of
      Drosophila melanogaster and D. simulans.
AB  - Scavenger receptor proteins are involved in the cellular internalization of a
      broad variety of foreign material, including pathogenic bacteria during
      phagocytosis. I find here that nonsynonymous divergence in three class C
      scavenger receptors (Sr-C's) between Drosophila melanogaster and D. simulans and
      between each of these species and D. yakuba is approximately four times the
      typical genome average. These genes also exhibit unusually high levels of
      segregating nonsynonymous polymorphism in D. melanogaster and D. simulans
      populations. A fourth Sr-C is comparatively conserved. McDonald-Kreitman tests
      reveal a significant excess of replacement fixations between D. melanogaster and
      D. simulans in the Sr-C's, but tests of polymorphic site frequency spectra do not
      support models of directional selection. It is possible that the molecular
      functions of SR-C proteins are sufficiently robust to allow exceptionally high
      amino acid substitution rates without compromising organismal fitness.
      Alternatively, SR-Cs may evolve under diversifying selection, perhaps as a result
      of pressure from pathogens. Interestingly, Sr-CIII and Sr-CIV are polymorphic for
      premature stop codons. Sr-CIV is also polymorphic for an in-frame 101-codon
      deletion and for the absence of one intron.

PMID- 15716506
TI  - Mutations in the Saccharomyces cerevisiae LSM1 gene that affect mRNA decapping
      and 3' end protection.
AB  - The decapping of eukaryotic mRNAs is a key step in their degradation. The
      heteroheptameric Lsm1p-7p complex is a general activator of decapping and also
      functions in protecting the 3' ends of deadenylated mRNAs from a 3'-trimming
      reaction. Lsm1p is the unique member of the Lsm1p-7p complex, distinguishing that
      complex from the functionally different Lsm2p-8p complex. To understand the
      function of Lsm1p, we constructed a series of deletion and point mutations of the
      LSM1 gene and examined their effects on phenotype. These studies revealed the
      following: (i) Mutations affecting the predicted RNA-binding and inter-subunit
      interaction residues of Lsm1p led to impairment of mRNA decay, suggesting that
      the integrity of the Lsm1p-7p complex and the ability of the Lsm1p-7p complex to
      interact with mRNA are important for mRNA decay function; (ii) mutations
      affecting the predicted RNA contact residues did not affect the localization of
      the Lsm1p-7p complex to the P-bodies; (iii) mRNA 3'-end protection could be
      indicative of the binding of the Lsm1p-7p complex to the mRNA prior to activation
      of decapping, since all the mutants defective in mRNA 3' end protection were also
      blocked in mRNA decay; and (iv) in addition to the Sm domain, the C-terminal
      domain of Lsm1p is also important for mRNA decay function.

PMID- 15716508
TI  - Bayesian estimation of recent migration rates after a spatial expansion.
AB  - Approximate Bayesian computation (ABC) is a highly flexible technique that allows
      the estimation of parameters under demographic models that are too complex to be
      handled by full-likelihood methods. We assess the utility of this method to
      estimate the parameters of range expansion in a two-dimensional stepping-stone
      model, using samples from either a single deme or multiple demes. A minor
      modification to the ABC procedure is introduced, which leads to an improvement in
      the accuracy of estimation. The method is then used to estimate the expansion
      time and migration rates for five natural common vole populations in Switzerland
      typed for a sex-linked marker and a nuclear marker. Estimates based on both
      markers suggest that expansion occurred <10,000 years ago, after the most recent
      glaciation, and that migration rates are strongly male biased.

PMID- 15716509
TI  - Mapping quantitative trait loci using naturally occurring genetic variance among
      commercial inbred lines of maize (Zea mays L.).
AB  - Many commercial inbred lines are available in crops. A large amount of genetic
      variation is preserved among these lines. The genealogical history of the inbred
      lines is usually well documented. However, quantitative trait loci (QTL)
      responsible for the genetic variances among the lines are largely unexplored due
      to lack of statistical methods. In this study, we show that the pedigree
      information of the lines along with the trait values and marker information can
      be used to map QTL without the need of further crossing experiments. We develop a
      Monte Carlo method to estimate locus-specific identity-by-descent (IBD) matrices.
      These IBD matrices are further incorporated into a mixed-model equation for
      variance component analysis. QTL variance is estimated and tested at every
      putative position of the genome. The actual QTL are detected by scanning the
      entire genome. Applying this new method to a well-documented pedigree of maize
      (Zea mays L.) that consists of 404 inbred lines, we mapped eight QTL for the
      maize male flowering trait, growing degree day heat units to pollen shedding
      (GDUSHD). These detected QTL contributed >80% of the variance observed among the
      inbred lines. The QTL were then used to evaluate all the inbred lines using the
      best linear unbiased prediction (BLUP) technique. Superior lines were selected
      according to the estimated QTL allelic values, a technique called marker-assisted
      selection (MAS). The MAS procedure implemented via BLUP may be routinely used by
      breeders to select superior lines and line combinations for development of new
      cultivars.

PMID- 15716511
TI  - Now hear this.

PMID- 15716510
TI  - Gene expression analysis of the function of the male-specific lethal complex in
      Drosophila.
AB  - Dosage compensation refers to the equal expression of X-linked genes despite the
      difference in copy number between the two sexes. The male-specific lethal (MSL)
      complex is concentrated on the X chromosome in males. A gene expression assay for
      embryos was developed to examine the function of this complex. In mutant male
      embryos without either the MSL complex or MOF histone acetylase, dosage
      compensation is retained but autosomal expression is increased. Dosage
      compensation is lost in the double-mutant embryos. In embryos in which the MSL
      complex and MOF are targeted to the X chromosomes in females, the results are
      consistent with previous surveys showing that in general the X expression remains
      unchanged, but autosomal expression is reduced. Mutations in the ISWI chromatin
      remodeling component cause increases specifically of X-linked genes in males.
      Thus, the function of the MSL complex in conjunction with ISWI is postulated to
      override the effect on gene expression of high histone acetylation on the male X.
      The basic determinant of dosage compensation is suggested to be an inverse dosage
      effect produced by an imbalance of transcription factors on the X vs. the
      autosomes. The sequestration of the MSL complex to the male X may have evolved to
      counteract a similar effect on the autosomes and to prevent an overexpression of
      the X chromosome in males that would otherwise occur due to the high levels of
      histone acetylation.

PMID- 15716512
TI  - Short circuit, long life.

PMID- 15716513
TI  - More is less: neurogenesis and age-related cognitive decline in Long-Evans rats.
AB  - A reduction in the ability to generate new neurons in the brain has been
      suggested to contribute to cognitive decline with advanced age. In an outbred
      model strain of Long-Evans rats, cognitive performance as a function of age is
      variable in assessments of hippocampal-dependent spatial memory. Recent research
      indicates that greater hippocampal neurogenesis accompanies diminished cognitive
      abilities in older Long-Evans rats. These findings imply that the role of
      neurogenesis might change between youth and old age, and that further work is
      needed to understand the potential benefits and liabilities that new neurons may
      afford an aging brain.

PMID- 15716514
TI  - Trigeminal autonomic cephalalgias: fancy term or constructive change to the IHS
      classification?

PMID- 15716515
TI  - Action of cholinesterase inhibitors in patients' brains.

PMID- 15716516
TI  - Recreational cannabis use: not so harmless!

PMID- 15716517
TI  - Functional symptoms in neurology: questions and answers.
AB  - Between 10 and 30% of patients seen by neurologists have symptoms for which there
      is no current pathophysiological explanation. The objective of this review is to
      answer questions many neurologists have about disorders characterised by
      unexplained symptoms (functional disorders) by conducting a multidisciplinary
      review based on published reports and clinical experience. Current concepts
      explain functional symptoms as resulting from auto-suggestion, innate coping
      styles, disorders of volition or attention. Predisposing, precipitating, and
      perpetuating aetiological factors can be identified and contribute to a
      therapeutic formulation. The sympathetic communication of the diagnosis by the
      neurologist is important and all patients should be screened for psychiatric or
      psychological symptoms because up to two thirds have symptomatic psychiatric
      comorbidity. Treatment programmes are likely to be most successful if there is
      close collaboration between neurologists, (liaison) psychiatrists, psychologists,
      and general practitioners. Long term, symptoms persist in over 50% of patients
      and many patients remain dependent on financial help from the government.
      Neurologists can acquire the skills needed to engage patients in psychological
      treatment but would benefit from closer working relationships with liaison
      psychiatry or psychology.

PMID- 15716518
TI  - Degree of inhibition of cortical acetylcholinesterase activity and cognitive
      effects by donepezil treatment in Alzheimer's disease.
AB  - OBJECTIVES: To determine in vivo cortical acetylcholinesterase (AChE) activity
      and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14)
      prior to and after 12 weeks of donepezil therapy. METHODS: Cognitive and N
      [(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission
      tomography (PET) assessments before and after donepezil therapy. RESULTS:
      Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical
      donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p<0.0001). Enzyme
      inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t = 
      14.1; p<0.0001). Donepezil induced cortical inhibition of AChE activity
      correlated with changes in the Stroop Color Word interference scores (R(2) =
      0.59, p<0.01), but not with primary memory test scores. Analysis of the Stroop
      test data indicated that subjects with AChE inhibition greater than the median
      value (>22.2%) had improved scores on the Stroop Color Word Test compared with
      subjects with less inhibition who had stable to worsening scores (t = -2.7;
      p<0.05). CONCLUSIONS: Donepezil induced inhibition of cortical AChE enzyme
      activity is modest in patients with mild AD. The degree of cortical enzyme
      inhibition correlates with changes in executive and attentional functions.

PMID- 15716519
TI  - Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer's
      disease.
AB  - OBJECTIVE: To investigate the possibility that response to cholinesterase
      inhibitor therapy could be predicted by easily measurable variables that are
      known to change as a result of treatment (such as the Mini Mental State
      Examination), measures of function (such as the instrumental activities of daily
      living and the social behaviour subscales of the Nurse's Observation Scale for
      Geriatric Patients), and measures of attention (such as the Digit Symbol
      Substitution Test; DSST), or that might influence response through structural
      (for example, age, cerebrovascular disease, medial temporal lobe (MTL) atrophy,
      hypertension) or chemical (for example, smoking) mechanisms. METHOD: This was a
      cohort study of 160 consecutive outpatients with probable Alzheimer's disease who
      commenced cholinesterase inhibitor treatment over a 3 year period in a semi-rural
      area of Scotland. RESULTS: The overall response rate was 42.1%. Stratification of
      response between good and poor responders was possible using baseline DSST and a
      measure of MTL thickness using CT. Among the patients, 60.4% of those above the
      cut off point for both DSST and MTL thickness (29/48 subjects) were classified as
      good responders, compared with 6.3% of subjects below the cut off point for both
      (1/16 subjects). Subjects above the cut off point for both measures were more
      likely to be classified as good responders than subjects with only one or no
      values above the respective cut off points (chi(2) = 10.61, df = 1, p = 0.001)
      CONCLUSIONS: The DSST and a measure of MTL thickness derived from CT scanning may
      be useful in improving the prediction of response to cholinesterase inhibitors in
      subjects with AD. Subjects with low DSST scores and more severe MTL atrophy are
      unlikely to respond to treatment. These preliminary data justify a prospective
      trial of the usefulness of our suggested predictive measures.

PMID- 15716520
TI  - Involvement of the peripheral nervous system in human prion diseases including
      dural graft associated Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: To investigate abnormal prion protein (PrP) deposition in the
      peripheral nervous system (PNS) in human prion diseases. METHODS: Eight patients
      with prion diseases were examined: three with sporadic Creutzfeldt-Jakob disease
      (sCJD), two with dural graft associated CJD (dCJD), one with Gerstmann-Straussler
      Scheinker disease (GSS) with a PrP P102L mutation (GSS102), and two with a P105L
      mutation (GSS105). An atypical case of sCJD with PrP plaques in the brain
      presented clinically with peripheral neuropathy, and showed demyelination in 12%
      of the teased fibres of the sural nerve. The PNS was investigated by
      immunohistochemical and western blotting analyses of PrP. RESULTS: In
      immunohistochemical studies, granular PrP deposits were detected in some neurones
      of dorsal root ganglia and a few fibres of peripheral nerves and spinal posterior
      roots in one sCJD and two dCJD patients, but not in GSS102 or GSS105 patients.
      The atypical case of sCJD with peripheral neuropathy showed no obvious PrP
      deposition in the nerves. Western blotting analysis of the PNS from the dCJD
      patients revealed a small amount of protease K resistant PrP in the dorsal root
      ganglia and peripheral nerves. CONCLUSIONS: Abnormal PrP deposition occurs in the
      dorsal root ganglia and peripheral nerves in sCJD and dCJD. The PrP deposits in
      the PNS are not correlated with clinical manifestation of peripheral neuropathy
      in CJD.

PMID- 15716521
TI  - The neuropsychology of variant CJD: a comparative study with inherited and
      sporadic forms of prion disease.
AB  - OBJECTIVE: To assess cognitive function in variant Creutzfeldt-Jakob disease
      (vCJD). We describe the neuropsychological profiles of 10 cases and compare these
      data with cross sectional data obtained from patients with histologically
      confirmed sporadic CJD and cases with inherited prion disease with confirmed
      mutations in the prion protein gene. METHODS: Patients referred to the Specialist
      Cognitive Disorders Clinic at the National Hospital for Neurology and
      Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for
      further investigation of suspected CJD were recruited into the study. The
      neuropsychological test battery evaluated general intelligence, visual and verbal
      memory, nominal skills, literacy skills, visual perception and visuospatial
      functions, and visuospatial and executive function. RESULTS: The results indicate
      that moderate to severe cognitive decline is a characteristic feature of vCJD.
      Specifically, verbal and visual memory impairments and executive dysfunction were
      pervasive in all disease groups. Nominal skills were impaired in variant and
      sporadic CJD, significantly so when compared with the inherited prion disease
      group. Perceptual impairment was less frequent in the vCJD group than in the
      sporadic and inherited groups. CONCLUSION: This study confirms the occurrence of
      generalised cognitive decline in patients with vCJD. Although decline in
      cognitive function ultimately affects all domains, there is a suggestion that
      some components of visual perception may be spared in vCJD. The results also
      suggest that nominal function may be preserved in some cases with inherited prion
      disease.

PMID- 15716522
TI  - Incidence and mutation rates of Huntington's disease in Spain: experience of 9
      years of direct genetic testing.
AB  - BACKGROUND: Prior to the discovery of the Huntington's disease (HD) mutation, the
      prevalence, incidence, and new mutation rates for this disease were based on the
      presence of progressive choreic movements and a positive family history.
      OBJECTIVE: To evaluate the uptake of the HD genetic analysis in Spain, and to
      provide additional information on the epidemiology of this disease from the
      experience of 9 years of direct genetic testing. METHODS: From 1994 to 2002, CAG
      repeat length was determined in 317 patients with symptoms compatible with HD. In
      all cases, demographic, clinical, and family data were carefully reviewed.
      RESULTS: HD diagnosis (CAG repeat length >/=36) was confirmed in 166 (52%)
      symptomatic cases. Of these, 76 (45.8%) reported a positive family history and in
      21 cases (12.7%) family history was negative. New mutation events were
      genetically proven in three families and highly suspected in another, estimating
      that the minimum new mutation rate for HD in our population is >4%, with a
      potential mutation rate of 8%. More than 16% of all HD cases had late onset (>59
      years) of symptoms, and in three quarters of these the family history was
      negative. The incidence rate for the autonomous communities of Navarra and the
      Basque country, based on the number of newly diagnosed cases by genetic testing,
      was 4.7 per million per year. CONCLUSIONS: Direct HD genetic testing shows that
      the incidence and mutation rates of the disease are 2-3 times higher than
      previously reported. We also demonstrated the relevance of CAG repeat length
      assessment in diagnosing patients with late onset of symptoms and negative family
      history for HD.

PMID- 15716523
TI  - Heterogeneity of Parkinson's disease in the early clinical stages using a data
      driven approach.
AB  - OBJECTIVE: To investigate the heterogeneity of idiopathic Parkinson's disease
      (PD) in a data driven manner among a cohort of patients in the early clinical
      stages of the disease meeting established diagnostic criteria. METHODS: Data on
      demographic, motor, mood, and cognitive measures were collected from 120
      consecutive patients in the early stages of PD (Hoehn and Yahr I-III) attending a
      specialist PD research clinic. Statistical cluster analysis of the data allowed
      the existence of the patient subgroups generated to be explored. RESULTS: The
      analysis revealed four main subgroups: (a) patients with a younger disease onset;
      (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup
      with significant levels of cognitive impairment and mild depression; and (d) a
      subgroup with rapid disease progression but no cognitive impairment. CONCLUSIONS:
      This study complements and extends previous research by using a data driven
      approach to define the clinical heterogeneity of early PD. The approach adopted
      in this study for the identification of subgroups of patients within Parkinson's
      disease has important implications for generating testable hypotheses on defining
      the heterogeneity of this common condition and its aetiopathological basis and
      thus its treatment.

PMID- 15716524
TI  - Admission blood glucose and short term survival in primary intracerebral
      haemorrhage: a population based study.
AB  - BACKGROUND: The role of admission blood glucose level on the prognosis of
      patients with intracerebral haemorrhage has not been elucidated. OBJECTIVE: To
      examine this association on the basis of an epidemiologically representative
      patient material. METHODS: 249 500 people living in the catchment area of the
      Central Hospital of Central Finland. The diagnosis of ICH was established if
      verified by cranial computed tomography (CT) or autopsy. RESULTS: Of the 416
      patients who fulfilled the diagnostic criteria, 30 died before admission and 386
      were admitted to the Central Hospital. All 329 patients (290 nondiabetics and 39
      diabetics) with both admission blood glucose and cranial CT data were included in
      the study. The mean blood glucose level was 10.6 mmol/l for nondiabetics who died
      on the day of onset, 8.6 mmol/l for those dying during days 1 to 28, and 6.8
      mmol/l for the 28 day survivors. The corresponding figures for diabetics were
      13.9 mmol/l, 12.5 mmol/l, and 9.3 mmol/l. In both nondiabetics and diabetics,
      patients who died had significantly higher mean glucose than the 28 day survivors
      (p<0.0001 versus p = 0.029). However, blood glucose of the surviving diabetics
      was as high as that of the deceased nondiabetics (9.3 mmol/l versus 9.1 mmol/l).
      In nondiabetics, admission blood glucose was associated with parameters
      signifying severe stroke; disturbed consciousness, large haematoma volume and
      shift of cerebral midline structures, and high admission mean arterial pressure.
      In logistic regression analysis, high admission blood glucose in nondiabetics was
      a significant predictor of death during the first 28 days of onset (odds ratio
      1.22, 95% CI 1.07 to 1.40). CONCLUSIONS: High admission blood glucose predicts
      increased 28 day case fatality rate in both nondiabetic and diabetic patients
      with ICH. Because high admission blood glucose was associated with markers of
      severe stroke, we are inclined to support the stress theory; high admission blood
      glucose is the result of a serious ICH.

PMID- 15716525
TI  - Early computed tomography features in extensive middle cerebral artery territory
      infarct: prediction of survival.
AB  - BACKGROUND: To assess the predictive value of prognosis of different computed
      tomography (CT) features and National Institutes of Health Stroke Scale score
      (NIHSS) in acute extensive middle cerebral artery (MCA) infarct. METHODS: Fifty
      five patients with acute extensive MCA infarct had the CT performed within 24
      hours of the onset of symptoms. A total of 11 CT features were analysed. The age
      distribution, presence of risk factors, presence of individual CT feature, the
      total CT score, and the NIHSS were correlated with the 30 day mortality. RESULTS:
      Single explanatory variable analysis showed NIHSS, presence of midline shift,
      midline shift of more than 1 cm, extent of infarct, presence of hydrocephalus,
      effacement of subarachnoid space/cella media, attenuation of corticomedullary
      differentiation, and total CT score were associated with the 30 day mortality.
      Both extent of infarct >67% and attenuation of corticomedullary differentiation
      gave a sensitivity and specificity of 93% and 95%, respectively, for the
      prediction of survival. Logistic regression analysis showed that the extent of
      infarct and NIHSS were the only independent predictors. CONCLUSIONS: CT features
      and admission NIHSS are important parameters for prediction of survival in
      extensive MCA infarct.

PMID- 15716526
TI  - Incidence and diagnosis of anosognosia for hemiparesis revisited.
AB  - BACKGROUND: In previous studies, the incidence of anosognosia for hemiparesis has
      varied between 17% and 58% in samples of brain damaged patients with hemiparesis.
      OBJECTIVE: To determine whether this wide variation might be explained by the
      different criteria used for diagnosing anosognosia. METHODS: 128 acute stroke
      patients with hemiparesis or hemiplegia were tested for anosognosia for
      hemiparesis using the anosognosia scale of Bisiach et al. RESULTS: 94% of the
      patients who were rated as having "mild anosognosia"-that is, they did not
      acknowledge their hemiparesis spontaneously following a general question about
      their complaints-suffered from, and mentioned, other neurological deficits such
      as dysarthria, ptosis, or headache. However, they immediately acknowledged their
      paresis when they were asked about the strength of their limbs. Their other
      deficits clearly had a greater impact. These patients had significantly milder
      paresis than those who denied their disorder even when asked directly about their
      limbs. CONCLUSIONS: Patients who do not mention their paresis spontaneously but
      do so when questioned about it directly should not be diagnosed having
      "anosognosia." If this more conservative cut off criterion is applied to the data
      of the present as well as previous studies, a frequency of between 10% and 18%
      for anosognosia for hemiparesis is obtained in unselected samples of acute
      hemiparetic stroke patients. The incidence thus seems smaller than previously
      assumed.

PMID- 15716527
TI  - White matter hyperintensities are related to physical disability and poor motor
      function.
AB  - OBJECTIVE: To determine the impact of white matter hyperintensities (WMHs) on
      physical health and cognitive function in 60-64 year old individuals residing in
      the community. METHODS: A subsample of 478 persons aged 60-64 from a larger
      community sample underwent brain magnetic resonance imaging (MRI) scans. WMHs on
      T2 weighted FLAIR (fluid attenuated inversion recovery) MRI scans were assessed
      using an automated procedure. Subjects were assessed for global cognitive
      function, episodic memory, working memory (digit span), information processing
      speed (Symbol Digit Modalities Test; SDMT), fine motor dexterity (Purdue
      Pegboard), and grip strength, and completed the Physical Component Summary of the
      Short Form Health Survey (SF-12). Regression analyses were used to examine the
      effect of WMHs on physical and cognitive function. RESULTS: Deep and
      periventricular WMHs were present in all subjects, with women having slightly
      more lesions than men. WMHs were significantly associated with poorer reported
      physical health on the SF-12 scale, after adjusting for depression, cognitive
      function, and brain atrophy. WMHs were also related to lower scores on the Purdue
      Pegboard test, grip strength, choice reaction time, and SDMT, but not on tests of
      episodic memory, working memory, general intellectual function, and global
      cognitive function. On regression analyses, the Purdue Pegboard test and grip
      strength were related to physical disability. CONCLUSION: WMHs are common, albeit
      mild, in middle adult life. They are associated with physical disability,
      possibly through reduced speed, fine motor coordination, and muscular strength.
      They are also related to slowed information processing speed but not other
      cognitive functions.

PMID- 15716528
TI  - Giant calcified chronic subdural haematoma: a long term complication of shunted
      hydrocephalus.

PMID- 15716529
TI  - Ten year recurrence after first ever stroke in a Japanese community: the Hisayama
      study.
AB  - BACKGROUND: Very few population based cohort studies have focused on the long
      term recurrence of stroke. OBJECTIVE: To examine 10 year cumulative recurrence
      rates for stroke in a Japanese cohort according to pathological type and clinical
      subtype of brain infarction. METHODS: During a 32 year follow up of 1621 subjects
      >/=40 years of age, 410 developed first ever stroke. These were followed up
      prospectively for 10 years after stroke onset. RESULTS: During follow up, 108
      (26%) experienced recurrent stroke. The cumulative recurrence rates were 35.3% at
      five years and 51.3% at 10 years. The 10 year recurrence rates of subarachnoid
      haemorrhage (SAH), brain haemorrhage, and brain infarction were 70.0%, 55.6%, and
      49.7%, respectively; the difference between SAH and brain infarction was
      significant (p = 0.004). Most recurrent episodes after SAH or brain haemorrhage
      happened within a year after the index stroke, whereas recurrence of brain
      infarction increased consistently throughout the observation period.
      Cardioembolic stroke had a higher recurrence rate (75.2%) than lacunar infarction
      (46.8%) (p = 0.049). The 10 year risk of stroke recurrence increased with age
      after lacunar or atherothrombotic brain infarction, but not after the other types
      or subtypes. After atherothrombotic brain infarction, cardioembolic stroke, or
      SAH, the type and subtype of most recurrent strokes were the same as for the
      index stroke, but recurrence after lacunar infarction or brain haemorrhage showed
      divergent patterns. CONCLUSIONS: Japanese people have higher recurrence rates of
      stroke than other populations. Recurrence rate after a first brain infarct
      increases consistently through the next 10 years.

PMID- 15716530
TI  - Effects of peripheral cooling on intention tremor in multiple sclerosis.
AB  - OBJECTIVE: To investigate the effect of peripheral sustained cooling on intention
      tremor in patients with multiple sclerosis (MS). MS induced upper limb intention
      tremor affects many functional activities and is extremely difficult to
      treat.Materials/ METHODS: Deep (18 degrees C) and moderate (25 degrees C) cooling
      interventions were applied for 15 minutes to 23 and 11 tremor arms of patients
      with MS, respectively. Deep and moderate cooling reduced skin temperature at the
      elbow by 13.5 degrees C and 7 degrees C, respectively. Evaluations of
      physiological variables, the finger tapping test, and a wrist step tracking task
      were performed before and up to 30 minutes after cooling. RESULTS: The heart rate
      and the central body temperature remained unchanged throughout. Both cooling
      interventions reduced overall tremor amplitude and frequency proportional to
      cooling intensity. Tremor reduction persisted during the 30 minute post cooling
      evaluation period. Nerve conduction velocity was decreased after deep cooling,
      but this does not fully explain the reduction in tremor amplitude or the effects
      of moderate cooling. Cooling did not substantially hamper voluntary movement
      control required for accurate performance of the step tracking task. However,
      changes in the mechanical properties of muscles may have contributed to the
      tremor amplitude reduction. CONCLUSIONS: Cooling induced tremor reduction is
      probably caused by a combination of decreased nerve conduction velocity, changed
      muscle properties, and reduced muscle spindle activity. Tremor reduction is
      thought to relate to decreased long loop stretch reflexes, because muscle spindle
      discharge is temperature dependent. These findings are clinically important
      because applying peripheral cooling might enable patients to perform functional
      activities more efficiently.

PMID- 15716531
TI  - Neuropsychiatric porphyria in patients with refractory epilepsy: report of three
      cases.
AB  - OBJECTIVES: Although epileptic seizures are an infrequent feature of acute
      attacks of the neuropsychiatric porphyrias, there are no significant reports of
      porphyria in chronic epilepsy. This paper attempts to redress the balance.
      METHODS: Three case reports, including detailed laboratory and molecular
      diagnostics. RESULTS: Two patients with variegate porphyria and one with acute
      intermittent porphyria, referred within 1 year to a specialist porphyria service,
      with a long history of chronic refractory epileptic seizures, are described.
      CONCLUSIONS: Porphyria may be an aetiological factor in some cases of chronic
      refractory partial or generalised epilepsy. Porphyria should also be considered
      if addition of a new anti-epileptic medication causes a major deterioration in
      the epilepsy.

PMID- 15716534
TI  - Lower urinary tract function in patients with pituitary adenoma compressing
      hypothalamus.
AB  - BACKGROUND: The micturition reflex is under the tonic influence of suprapontine
      structures including the anteromedial frontal cortex, basal ganglia, and
      hypothalamus. However, there have been few reports about the role of the
      hypothalamus on the lower urinary tract (LUT) function in humans. OBJECTIVE: To
      investigate LUT function in patients with pituitary adenomas. METHODS: Urodynamic
      studies were carried out in three patients with LUT symptoms who had pituitary
      adenomas extending upwards to the hypothalamus. RESULTS: All three male patients
      (age 28 to 62 years) developed LUT symptoms (urinary urgency and frequency (3);
      urinary incontinence (3); voiding difficulty and retention (2)) along with weight
      loss, psychiatric symptoms, unsteady gait, and/or visual disturbances. One had
      the syndrome of inappropriate secretion of antidiuretic hormone, but none had
      diabetes insipidus. Two had resection of the tumour and subsequent radiation
      therapy, but LUT dysfunction persisted. The third patient had partial resection
      of the tumour to ameliorate hydrocephalus. Urodynamic studies showed detrusor
      overactivity during the storage phase in all patients; during the voiding phase
      there was underactive detrusor in two and non-relaxing sphincter in one.
      CONCLUSIONS: Hypothalamic lesions can cause severe LUT dysfunction in both the
      storage and voiding phases of micturition. This may reflect the crucial role of
      the hypothalamus in regulating micturition in humans.

PMID- 15716532
TI  - Vagus nerve stimulation: predictors of seizure freedom.
AB  - OBJECTIVES: To identify predictive factors for the seizure-free outcome of vagus
      nerve stimulation (VNS). METHODS: All 47 patients who had undergone VNS
      implantation at one centre and had at least one year of follow up were studied.
      They underwent complete presurgical evaluation including detailed clinical
      history, magnetic resonance imaging, and long term video-EEG with ictal and
      interictal recordings. After implantation, adjustment of stimulation parameters
      and concomitant antiepileptic drugs were at the discretion of the treating
      physician. RESULTS: Mean (SD) age of the patients was 22.7 (11.6) years (range 7
      to 53). Six patients (13%) became seizure-free after the VNS implantation. Only
      two variables showed a significant association with the seizure-free outcome:
      absence of bilateral interictal epileptiform discharges (IED) and presence of
      malformation of cortical development (MCD). Epilepsy duration showed a non
      significant trend towards a negative association with outcome. By logistic
      regression analysis, only absence of bilateral IED correlated independently with
      successful VNS treatment (p<0.01, odds ratio = 29.2 (95% confidence interval, 2.4
      to 353)). Bilateral IED (independent or bilateral synchronous) was found in one
      of six seizure-free patients and in 33 of 41 non-seizure-free patients. When
      bilateral IED were absent, the sensitivity for seizure-free outcome was 0.83
      (0.44 to 0.97), and the specificity was 0.80 (0.66 to 0.90). CONCLUSIONS:
      Bilateral IED was independently associated with the outcome of VNS. These results
      are preliminary because they were based on a small patient population. They may
      facilitate prospective VNS studies enrolling larger numbers of patients to
      confirm the results.

PMID- 15716535
TI  - Late mortality after head injury.
AB  - OBJECTIVES: To investigate mortality trends in a cohort of people admitted to a
      regional head injury unit with all severities of injury in the calendar year
      1981. METHODS: A computerised database with details of 1919 admissions was
      compared with deaths registered by the NHS Central Register, Scotland for the
      years 1981 to mid-2002. Death certificate information for matches was analysed.
      RESULTS: The 1919 admissions referred to 1871 individuals, comprising 93 severe,
      205 moderate, and 1573 minor injuries according to Glasgow coma scale criteria.
      There were 57 deaths (42 severe head injuries, eight moderate, seven minor)
      during the initial admission, and 340 (six severe, 33 moderate, 301 minor) in the
      subsequent years. Substance abuse, principally alcohol, was a factor in 37
      deaths, suicide accounted for 20, and accidents for 25. The great majority of
      these latter deaths were in people under the age of 70 years. CONCLUSION:
      Premature deaths after predominantly minor head injury are commonly alcohol
      related or the result of suicide or accidents.

PMID- 15716536
TI  - Identifying factors contributing to child and family outcome 30 months after
      traumatic brain injury in children.
AB  - OBJECTIVE: To examine the contributions of injury severity, physical and
      cognitive disability, child and family function to outcome 30 months after
      traumatic brain injury (TBI) in children. DESIGN: A prospective, longitudinal,
      between group design, comparing function before and after injury across three
      levels of injury severity. SUBJECTS: One hundred and fifty children, 3.0-12.11
      years old, admitted to hospital with a diagnosis of TBI. The sample was divided
      according to injury severity: mild (n = 42), moderate (n = 70), severe (n = 38).
      Children with a history of neurological, developmental, and psychiatric disorders
      were excluded from participation. MAIN OUTCOME MEASURES: Post injury physical
      function, cognitive ability (incorporating intellect, memory, and attention),
      behavioural and family functioning, and level of family burden. RESULTS: A dose
      response relation was identified for injury severity and physical and cognitive
      outcome, with significant recovery documented from acute to six months after TBI.
      Behavioural functioning was not related to injury severity, and where problems
      were identified, little recovery was noted over time. Family functioning remained
      unchanged from preinjury to post injury assessments. The level of family burden
      was high at both six and 30 months after injury, and was predicted by injury
      severity, functional impairment, and post injury child behavioural disturbance.
      CONCLUSIONS: These results suggest ongoing problems for the child and significant
      family burden 30 months after TBI. The nature and severity of the physical and
      cognitive problems are closely related to injury severity, with child and family
      function predicted by psychosocial and premorbid factors.

PMID- 15716537
TI  - Targeting the subthalamic nucleus for deep brain stimulation: technical approach
      and fusion of pre- and postoperative MR images to define accuracy of lead
      placement.
AB  - OBJECTIVES: To define the role of magnetic resonance imaging (MRI) and
      intraoperative electrophysiological recording in targeting the subthalamic
      nucleus (STN) in Parkinson's disease and to determine accuracy of electrode
      placement. PATIENTS AND METHODS: We implanted 54 electrodes into the STN in 27
      patients. Target planning was done by coordinate guidelines and visualising the
      STN on MRI and defined in relation to the mid-point of the AC-PC line.
      Intraoperative microelectrode recording was used. We adjusted electrode positions
      for placement in the centre of the STN electrical activity and verified this on
      postoperative MRI in 16 cases, which were fused to the preoperative images to
      measure actual error in electrode placement in the three axes. RESULTS: Based on
      coordinate calculation and MRI localisation, the mean of the target was 11.5 mm
      lateral, 2.5 mm posterior and 4.1 mm inferior to the mid-point of the AC-PC line.
      Fifty good electrophysiological recordings of the STN (average length 4.65 mm)
      were achieved and target point adjusted in 90% of lead placements. The mean of
      the final target after electrophysiological correction was 11.7 mm lateral, 2.1
      mm posterior, and 3.8 mm inferior to the mid-point. The distance from the centre
      of the electrode artefact to the final target used after electrophysiological
      recording on the fused images was 0.48 mm, 0.69 mm, and 2.9 mm in the x, y, and z
      axes, respectively. No postoperative MRI related complication was observed.
      CONCLUSION: Both direct visualisation of the STN on MRI and intraoperative
      electrophysiological recording are important in defining the best target.
      Individual variations exist in the location of the STN target. Fewer tracks were
      required to define STN activity on the side operated first. Our current
      stereotactic method of electrode placement is relatively accurate.

PMID- 15716538
TI  - The time course of visual field recovery following transphenoidal surgery for
      pituitary adenomas: predictive factors for a good outcome.
AB  - OBJECTIVE: To report the quantitative assessment of visual fields (VF) in
      patients with pituitary macroadenomas, and the time course and predictive factors
      for recovery of vision. METHODS: Retrospective study of 41 patients with
      pituitary adenomas and visual disturbance. Patients underwent pre- and
      postoperative VF assessment at one week, three to six months, one year, two
      years, and five years using the Humphrey field analyser, which gives a
      quantitative measure of VF in each quadrant. RESULTS: 36/41 patients (88%)
      presented with a visual disturbance. Mean (SEM) duration of symptoms was 94 (50)
      weeks (range 0.5 to 1500); 12 (29%) had optic atrophy at presentation. Impairment
      of VF was greatest in the upper temporal quadrant, followed by the lower
      temporal. VF recovery was progressive and apparent even at the five year follow
      up (p<0.001). Overall, VF returned to normal in 35% of eyes, improved in 60%, and
      remained unchanged in 5%. Patients whose VF returned to normal had a shorter
      duration of symptoms (16 (5) v 137 (56) weeks; p<0.05), better preoperative
      visual acuity (p<0.05), and a smaller degree of impairment in preoperative
      lateral quadrant VF (p<0.01) than those whose VF only improved. On multivariate
      analysis, the only predictive factor for VF recovery was the degree of impairment
      in VF preoperatively. CONCLUSIONS: Transphenoidal surgery for pituitary
      macroadenoma results in a progressive recovery of VF in 95% of patients. The
      extent of the VF recovery is mainly dependent on the preoperative VF deficit,
      which emphasises the need for early intervention in these patients.

PMID- 15716539
TI  - Cognitive bedside assessment in atypical parkinsonian syndromes.
AB  - BACKGROUND: Despite the growing recognition of the importance of cognitive
      symptoms for the diagnosis and management of atypical parkinsonian syndromes, the
      cognitive assessment of the patients in clinical practice often remains very
      limited. OBJECTIVES: To examine the ability of a brief and simple cognitive
      screening test to detect cognitive deficits in atypical parkinsonian syndromes.
      METHODS: Addenbrooke's cognitive examination (ACE), the mini-mental state
      examination (MMSE), and the dementia rating scale (DRS) were applied to 26
      patients with multiple system atrophy (MSA), 39 with progressive supranuclear
      palsy (PSP), and 25 with corticobasal degeneration (CBD). The results were then
      compared with those obtained in 30 healthy age matched volunteers and 30 patients
      with Alzheimer's disease. RESULTS: In all four diseases the rate of detection of
      cognitive impairment on ACE was higher than on MMSE and comparable with DRS. The
      severity of cognitive impairment was most pronounced in the CBD group, which
      showed a similar degree of impairment to the Alzheimer group. In contrast, MSA
      patients were the least cognitively impaired. The PSP group took an intermediate
      position. CONCLUSIONS: Cognitive impairment in atypical parkinsonian syndromes
      can be detected using a brief and clinically applicable bedside test such as ACE.

PMID- 15716540
TI  - Differentiation of Parkinson's disease and atypical parkinsonian syndromes by
      transcranial ultrasound.
AB  - Neuroimaging is known to complement clinical findings in the diagnostic work up
      of parkinsonian syndromes. Recently, transcranial ultrasound was reported to have
      a high diagnostic yield in differentiating idiopathic Parkinson's disease (IPD)
      from atypical parkinsonian syndromes. This report summarises the sonographic
      findings of 102 patients with IPD, 34 patients with multiple system atrophy, and
      21 patients with progressive supranuclear palsy. Increased echogenicity of the
      substantia nigra is predictive for IPD whereas a low echogenic substantia nigra,
      particularly when combined with a hyperechogenic lentiform nucleus, strongly
      suggests an atypical Parkinsonian syndrome. The underlying causes for the
      differential echo pattern of the substantia nigra remain unknown.

PMID- 15716542
TI  - Changes in motor cortex excitability during muscle fatigue in amyotrophic lateral
      sclerosis.
AB  - To further investigate the pathophysiology of amyotrophic lateral sclerosis
      (ALS), the silent period (SP) evoked by transcranial magnetic stimulation during
      a fatiguing muscle contraction was evaluated in 15 patients and in 15 healthy
      subjects. Physiological lengthening of the SP duration was not observed in
      patients with disease duration of > or = 2 years. Decreased intracortical
      inhibition, probably secondary to dysfunction of the inhibitory interneurons that
      modulate the corticomotoneuronal firing, appears in later stages of disease.
      Normal motor cortex adaptation is impaired and cortical hyperexcitability might
      be unmasked during fatigue in ALS patients with longer disease duration.

PMID- 15716541
TI  - Altered subthalamo-pallidal synchronisation in parkinsonian dyskinesias.
AB  - The aim of this work was to study the role of subthalamo-pallidal synchronisation
      in the pathophysiology of dyskinesias. We recorded local field potentials (LFPs)
      in a patient with Parkinson's disease and left surgery induced dyskinesias with
      double, bilateral deep brain stimulation electrode implants in the subthalamic
      nucleus (STN) and the globus pallidus internus (GPi). Synchronisation was studied
      through coherence analysis. In the nuclei contralateral to the dyskinetic side of
      the body there was decreased STN-GPi coherence in the high beta range (20-30 Hz)
      and an enhanced coherence at low frequencies (<10 Hz). Despite the possible
      limitations arising from single-case observations, our findings suggest that
      parkinsonian dyskinesias are related to altered synchronisation between different
      structures of the basal ganglia. Firing abnormalities within individual basal
      ganglia nuclei are probably not enough to account for the complex balance between
      hypokinetic and hyperkinetic symptoms in human parkinsonian dyskinesias and
      altered interactions between nuclei should also be considered.

PMID- 15716543
TI  - Neurometabolic coupling in the vegetative and minimally conscious states:
      preliminary findings.
AB  - The objective of this study was to determine the integrity of the homoeostatic
      coupling relationship between neuronal electrical function and cerebral
      metabolism in the vegetative and minimally conscious states. Ten patients who met
      recognised diagnostic criteria (six in the vegetative state and four minimally
      conscious) were investigated using simultaneous electroencephalography and
      positron emission tomography. It was found that the coupling between neuronal
      electrical activity and regional glucose metabolism was preserved in all the
      minimally conscious patients but was absent in all the vegetative state patients.
      Our preliminary results suggest patients in the vegetative state may endure an
      impaired coupling relation between neuronal electrical function and cerebral
      energy metabolism.

PMID- 15716544
TI  - Recurrent stroke associated with cannabis use.
AB  - Drug misuse represents a risk factor for cerebrovascular disease, especially
      among young people. Despite the fact that cannabis is the most widely used
      illicit drug, there are only a few reports associating its use with
      cerebrovascular disease. We describe a patient who suffered three ischaemic
      strokes immediately after cannabis consumption. Other stroke aetiologies were
      ruled out, and neuroimaging revealed infarcts in different arterial areas as well
      as evidence of non-atherosclerotic arterial disease, which suggests an underlying
      vasculopathy of uncertain (toxic or inflammatory) origin. Cannabis use may be
      associated with ischaemic stroke in young patients, but its mechanism is unclear.

PMID- 15716545
TI  - DWI in transient global amnesia and TIA: proposal for an ischaemic origin of TGA.
AB  - There are conflicting reports concerning signal intensity changes in transient
      global amnesia (TGA) using diffusion weighted imaging (DWI). We prospectively
      analysed DWI signal intensity changes in TIA and TGA patients, and compared the
      clinical characteristics and risk factors of both groups. Using DWI and
      conventional T1 and T2 weighted turbo spin echo sequences, 28 patients with acute
      TGA (13 men, mean age 61.5 years) and 74 TIA patients (47 men, mean age 62.4
      years) were studied within 48 hours after symptom onset. Every patient underwent
      an intensive diagnostic investigation. In 10/28 (36%) of the TGA patients and
      21/74 (28%) of the TIA patients, DWI signal intensity changes occurred. The time
      to DWI and the duration of symptoms were comparable in TIA and TGA patients.
      Overall, TIA patients showed an increased prevalence of vascular risk factors
      compared with TGA patients. In the TGA group, patients with abnormal DWI showed
      carotid atherosclerosis significantly more frequently. Based on our data, we
      suggest that the aetiology of TGA could be explained by an ischaemic event; due
      to arterial thrombembolic ischaemia in one subgroup, particularly in those
      patients with increased vascular risk factors, and due to venous ischaemia in
      another subgroup with valsalva-like activities before symptom onset.

PMID- 15716546
TI  - Historical note. Gabriel Anton's (1858-1933) contribution to the history of
      neurosurgery.

PMID- 15716547
TI  - Genotype-phenotype correlation in a family with late onset CMT and an MPZ
      lys236del mutation.
AB  - An in frame, lys236 deletion in the intracytoplasmic domain of myelin protein
      zero (MPZ) has recently been designated as a mutation possibly associated with
      Charcot-Marie-Tooth disease (CMT) but requiring further documentation. In this
      report we present a detailed clinical, electrophysiological, and genotype
      correlation in three generations of a family with the MPZ lys236del mutation and
      provide further evidence that this mutation is associated with CMT. The MPZ
      lys236del mutation is associated with an autosomal dominant, adult onset CMT
      phenotype, with variable penetrance ranging from an asymptomatic state to foot
      deformities, pedal numbness, and muscle cramps. Nerve conduction studies disclose
      intermediate range, somewhat non-uniform slowing of motor nerve conduction, which
      is accentuated in forelimb rather than distal nerve segments. Based on the
      contrasting finding of entirely normal conduction velocities (CV) in a
      genetically affected 15 year old in this family, it remains to be established
      whether CV slowing with this mutation is progressive in life, a pattern that
      would contrast with CMT1a (PMP22 gene duplication).

PMID- 15716548
TI  - Histology of hereditary neuralgic amyotrophy.
AB  - We report the findings in five muscle and three sural nerve biopsies, and in one
      postmortem plexus specimen, from six patients with hereditary neuralgic
      amyotrophy (HNA). We found that the sensory nerves are definitely involved in HNA
      despite the mainly motor symptoms, and that lesions in nerves and muscles are
      more widespread throughout the peripheral nervous system than clinically
      presumed, but, simultaneously, very focally affect isolated fascicles within
      individual nerves.

PMID- 15716549
TI  - Long-term treatment of generalised myasthenia gravis with FK506 (tacrolimus).
AB  - Efficacy and safety of long term use of FK506 (2-4.5 mg/day) for a maximum of two
      years were evaluated in 12 patients with generalised myasthenia gravis (MG). At
      the end of the study, eight patients (67%) showed improvement in either MG score
      or Activities in Daily Living score, and prednisolone dosage could be reduced in
      seven patients (58%), with a mean reduction ratio of 37%. Long term use of FK506
      for MG can be more effective than short term administration, with no serious side
      effects.

PMID- 15716550
TI  - 4-aminopyridine restores visual ocular motor function in upbeat nystagmus.
AB  - The effect of the potassium channel blocker 4-aminopyridine (4-AP) on spontaneous
      upbeat nystagmus (UBN) was investigated with the search coil technique during
      fixation in different gaze positions and smooth pursuit in a patient before and
      after ingestion of 10 mg 4-AP. UBN was reduced from 8.6 deg/s to 2.0 deg/s by 4
      AP causing subjective relief from distressing oscillopsia, and impaired upward
      smooth pursuit was restored (gains: before medication 0.38; after medication
      0.86). In the dark, UBN was slightly stronger and not affected by 4-AP. We
      propose that 4-AP improved the function of cerebellar pathways that mediate gaze
      holding and smooth pursuit by intensifying the excitability of cerebellar
      Purkinje cells.

PMID- 15716551
TI  - Possible transcallosal seizure induction by paired pulse transcranial magnetic
      stimulation in a patient with frontal lobe epilepsy.

PMID- 15716552
TI  - Hashimoto's encephalopathy: steroid resistance and response to intravenous
      immunoglobulins.

PMID- 15716553
TI  - Spontaneous lobar haemorrhage in CADASIL.

PMID- 15716554
TI  - Urinary retention caused by a small cortical infarction.

PMID- 15716555
TI  - Images in clinical medicine. Tinea circinata.

PMID- 15716556
TI  - Population and development--shifting paradigms, setting goals.

PMID- 15716557
TI  - Women, inequality, and the burden of HIV.

PMID- 15716558
TI  - Individual rights versus the public's health--100 years after Jacobson v.
      Massachusetts.

PMID- 15716559
TI  - The risk of cesarean delivery with neuraxial analgesia given early versus late in
      labor.
AB  - BACKGROUND: Epidural analgesia initiated early in labor (when the cervix is less
      than 4.0 cm dilated) has been associated with an increased risk of cesarean
      delivery. It is unclear, however, whether this increase in risk is due to the
      analgesia or is attributable to other factors. METHODS: We conducted a randomized
      trial of 750 nulliparous women at term who were in spontaneous labor or had
      spontaneous rupture of the membranes and who had a cervical dilatation of less
      than 4.0 cm. Women were randomly assigned to receive intrathecal fentanyl or
      systemic hydromorphone at the first request for analgesia. Epidural analgesia was
      initiated in the intrathecal group at the second request for analgesia and in the
      systemic group at a cervical dilatation of 4.0 cm or greater or at the third
      request for analgesia. The primary outcome was the rate of cesarean delivery.
      RESULTS: The rate of cesarean delivery was not significantly different between
      the groups (17.8 percent after intrathecal analgesia vs. 20.7 percent after
      systemic analgesia; 95 percent confidence interval for the difference, -9.0 to
      3.0 percentage points; P=0.31). The median time from the initiation of analgesia
      to complete dilatation was significantly shorter after intrathecal analgesia than
      after systemic analgesia (295 minutes vs. 385 minutes, P<0.001), as was the time
      to vaginal delivery (398 minutes vs. 479 minutes, P<0.001). Pain scores after the
      first intervention were significantly lower after intrathecal analgesia than
      after systemic analgesia (2 vs. 6 on a 0-to-10 scale, P<0.001). The incidence of
      one-minute Apgar scores below 7 was significantly higher after systemic analgesia
      (24.0 percent vs. 16.7 percent, P=0.01). CONCLUSIONS: Neuraxial analgesia in
      early labor did not increase the rate of cesarean delivery, and it provided
      better analgesia and resulted in a shorter duration of labor than systemic
      analgesia.

PMID- 15716560
TI  - N-terminal pro-B-type natriuretic peptide and long-term mortality in stable
      coronary heart disease.
AB  - BACKGROUND: The level of the inactive N-terminal fragment of pro-brain (B-type)
      natriuretic peptide (BNP) is a strong predictor of mortality among patients with
      acute coronary syndromes and may be a strong prognostic marker in patients with
      chronic coronary heart disease as well. We assessed the relationship between N
      terminal pro-BNP (NT-pro-BNP) levels and long-term mortality from all causes in a
      large cohort of patients with stable coronary heart disease. METHODS: NT-pro-BNP
      was measured in baseline serum samples from 1034 patients referred for
      angiography because of symptoms or signs of coronary heart disease. The rate of
      death from all causes was determined after a median follow-up of nine years.
      RESULTS: At follow-up, 288 patients had died. The median NT-pro-BNP level was
      significantly lower among patients who survived than among those who died (120 pg
      per milliliter [interquartile range, 50 to 318] vs. 386 pg per milliliter
      [interquartile range, 146 to 897], P<0.001). Patients with NT-pro-BNP levels in
      the highest quartile were older, had a lower left ventricular ejection fraction
      (LVEF) and a lower creatinine clearance rate, and were more likely to have a
      history of myocardial infarction, clinically significant coronary artery disease,
      and diabetes than patients with NT-pro-BNP levels in the lowest quartile. In a
      multivariable Cox regression model, the hazard ratio for death from any cause for
      the patients with NT-pro-BNP levels in the fourth quartile as compared with those
      in the first quartile was 2.4 (95 percent confidence interval, 1.5 to 4.0;
      P<0.001); the NT-pro-BNP level added prognostic information beyond that provided
      by conventional risk factors, including the patient's age; sex; family history
      with respect to ischemic heart disease; the presence or absence of a history of
      myocardial infarction, angina, hypertension, diabetes, or chronic heart failure;
      creatinine clearance rate; body-mass index; smoking status; plasma lipid levels;
      LVEF; and the presence or absence of clinically significant coronary artery
      disease on angiography. CONCLUSIONS: NT-pro-BNP is a marker of long-term
      mortality in patients with stable coronary disease and provides prognostic
      information above and beyond that provided by conventional cardiovascular risk
      factors and the degree of left ventricular systolic dysfunction.

PMID- 15716561
TI  - Effect of expedited treatment of sex partners on recurrent or persistent
      gonorrhea or chlamydial infection.
AB  - BACKGROUND: Many sex partners of persons with gonorrhea or chlamydial infections
      are not treated, which leads to frequent reinfections and further transmission.
      METHODS: We randomly assigned women and heterosexual men with gonorrhea or
      chlamydial infection to have their partners receive expedited treatment or
      standard referral. Patients in the expedited-treatment group were offered
      medication to give to their sex partners, or if they preferred, study staff
      members contacted partners and provided them with medication without a clinical
      examination. Patients assigned to standard partner referral were advised to refer
      their partners for treatment and were offered assistance notifying partners. The
      primary outcome was persistent or recurrent gonorrhea or chlamydial infection in
      patients 3 to 19 weeks after treatment. RESULTS: Persistent or recurrent
      gonorrhea or chlamydial infection occurred in 121 of 931 patients (13 percent)
      assigned to standard partner referral and 92 of 929 (10 percent) assigned to
      expedited treatment of sexual partners (relative risk, 0.76; 95 percent
      confidence interval, 0.59 to 0.98). Expedited treatment was more effective than
      standard referral of partners in reducing persistent or recurrent infection among
      patients with gonorrhea (3 percent vs. 11 percent, P=0.01) than in those with
      chlamydial infection (11 percent vs. 13 percent, P=0.17) (P=0.05 for the
      comparison of treatment effects) and remained independently associated with a
      reduced risk of persistent or recurrent infection after adjustment for other
      predictors of infection at follow-up (relative risk, 0.75; 95 percent confidence
      interval, 0.57 to 0.97). Patients assigned to expedited treatment of sexual
      partners were significantly more likely than those assigned to standard referral
      of partners to report that all of their partners were treated and significantly
      less likely to report having sex with an untreated partner. CONCLUSIONS:
      Expedited treatment of sex partners reduces the rates of persistent or recurrent
      gonorrhea or chlamydial infection.

PMID- 15716562
TI  - Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by
      coma.
AB  - In southern Vietnam, a four-year-old boy presented with severe diarrhea, followed
      by seizures, coma, and death. The cerebrospinal fluid contained 1 white cell per
      cubic millimeter, normal glucose levels, and increased levels of protein (0.81 g
      per liter). The diagnosis of avian influenza A (H5N1) was established by
      isolation of the virus from cerebrospinal fluid, fecal, throat, and serum
      specimens. The patient's nine-year-old sister had died from a similar syndrome
      two weeks earlier. In both siblings, the clinical diagnosis was acute
      encephalitis. Neither patient had respiratory symptoms at presentation. These
      cases suggest that the spectrum of influenza H5N1 is wider than previously
      thought.

PMID- 15716563
TI  - Memory dysfunction.

PMID- 15716564
TI  - Bites of brown recluse spiders and suspected necrotic arachnidism.

PMID- 15716565
TI  - Images in clinical medicine. Condylomata lata of secondary syphilis.

PMID- 15716566
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-2005. A 53-year-old man with depression and sudden shortness of
      breath.

PMID- 15716567
TI  - Pain relief during labor.

PMID- 15716568
TI  - Toward better control of sexually transmitted diseases.

PMID- 15716569
TI  - Attacking amyloid.

PMID- 15716570
TI  - Lymphoma-infiltrating immune cells.

PMID- 15716571
TI  - Interns' work hours.

PMID- 15716572
TI  - The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.

PMID- 15716573
TI  - Pump priming in heart surgery in infants.

PMID- 15716574
TI  - Family history.

PMID- 15716575
TI  - Doctors and drug companies.

PMID- 15716576
TI  - Hepatic arterial infusion after liver resection.

PMID- 15716577
TI  - The spatial organization of lipid synthesis in the yeast Saccharomyces cerevisiae
      derived from large scale green fluorescent protein tagging and high resolution
      microscopy.
AB  - The localization pattern of proteins involved in lipid metabolism in the yeast
      Saccharomyces cerevisiae was determined using C-terminal green fluorescent
      protein tagging and high resolution confocal laser scanning microscopy. A list of
      493 candidate proteins ( approximately 9% of the yeast proteome) was assembled
      based on proteins of known function in lipid metabolism, their interacting
      proteins, proteins defined by genetic interactions, and regulatory factors acting
      on selected genes or proteins. Overall 400 (81%) transformants yielded a positive
      green fluorescent protein signal, and of these, 248 (62% of the 400) displayed a
      localization pattern that was not cytosolic. Observations for many proteins with
      known localization patterns were consistent with published data derived from cell
      fractionation or large scale localization approaches. However, in many cases,
      high resolution microscopy provided additional information that indicated that
      proteins distributed to multiple subcellular locations. The majority of tagged
      enzymes localized to the endoplasmic reticulum (91), but others localized to
      mitochondria (27), peroxisomes (17), lipid droplets (23), and vesicles (53). We
      assembled enzyme localization patterns for phospholipid, sterol, and sphingolipid
      biosynthetic pathways and propose a model, based on enzyme localization, for
      concerted regulation of sterol and sphingolipid metabolism that involves
      shuttling of key enzymes between endoplasmic reticulum, lipid droplets, vesicles,
      and Golgi.

PMID- 15716578
TI  - The sterol response element binding protein regulates cyclooxygenase-2 gene
      expression in endothelial cells.
AB  - We previously demonstrated that cholesterol deprivation increases endothelial
      cyclooxygenase-2 (COX-2)-dependent prostacyclin [prostaglandin I2 (PGI2)]
      production in vitro. Cholesterol directly regulates gene transcription through
      the sterol response element binding protein (SREBP). In this work, we demonstrate
      that SREBP directly regulates COX-2 expression. Cholesterol reduces human COX-2
      promoter-luciferase reporter construct activity in transiently transfected
      endothelial cells. Conversely, cotransfection with a constitutively active mutant
      SREBP increases COX-2 promoter activity. SREBP-1a and -2 specifically bind a
      putative sterol response element (SRE) sequence in the COX-2 promoter. This
      sequence competes for SREBP binding to a low density lipoprotein receptor
      consensus sequence in an electromobility-shift assay. These data indicate that
      endothelial COX-2 is regulated by cholesterol via the SREBP pathway. The present
      study identifies COX-2 as the first vascular gene without a clear role in lipid
      metabolism transactivated by SREBP, and suggests that enhanced production of PGI2
      through this pathway may be an additional benefit of cholesterol-lowering
      therapies.

PMID- 15716579
TI  - Analysis of cell membrane aminophospholipids as isotope-tagged derivatives.
AB  - Glycerophosphoethanolamine (GPEtn) and glycerophosphoserine (GPSer) lipids were
      reacted with a multiplexed set of differentially isotopically enriched N
      methylpiperazine acetic acid N-hydroxysuccinimide ester reagents, which place
      isobaric mass labels at a primary amino group. The resulting derivatized
      aminophospholipids were isobaric and chromatographically indistinguishable but
      yielded positive reporter ions (m/z 114 or 117) after collisional activation that
      could be used to identify and quantify individual members of the multiplex set.
      The chromatographic and mass spectrometric response of N-methylpiperazine amide
      tagged aminophospholipids was probed using glycerophosphoethanolamine and
      glycerophosphoserine lipid standards. The [M+H]+ of each tagged aminophospholipid
      shifted 144 Da, and during collision-induced dissociation the major fragmentation
      ion was either m/z 114 or 117. This mode of detecting aminophospholipids was
      useful for an unbiased analysis of plasmalogen GPEtn lipids. Molecular species
      information on the esterified fatty acyl substituents was obtained by collisional
      activation of the [M-H]- ions. The isotope-tagged reagents were used to assess
      changes in the distribution of GPEtn lipids after exposure of liposomes made from
      phospholipids extracted from RAW 264.7 cells to Cu2+/H2O2 to illustrate the
      ability of these reagents to aid in the mass spectrometric identification of
      aminophospholipid changes that occur during biological stimuli.

PMID- 15716580
TI  - Endotoxin promotes preferential periportal upregulation of VLDL secretion in the
      rat liver.
AB  - Zonation affects liver parenchymal cell function and metabolism as well as
      nonparenchymal cell activation, but whether VLDL production is zonated has yet to
      be elucidated. Infection induces enhanced VLDL secretion by the liver. Ex vivo
      studies were undertaken to examine the liver heterogeneity for VLDL formation and
      secretion and their in vivo response to endotoxin. Highly pure periportal (PP)
      and perivenous (PV) hepatocytes were isolated from fasted lipopolysaccharide
      treated, fasted, and fed rats. They were used to assess their capacity to release
      VLDL-apolipoprotein B (apoB) and lipid classes in relation to de novo lipid
      synthesis and the expression of genes crucial to VLDL production. Despite the
      common superior ability of PP hepatocytes for lipid release and zonal differences
      in lipid synthesis, zonated secretion of VLDL particles was observed in septic
      but not in normal fed or fasted livers. The endotoxin-induced apoB secretion was
      more accentuated in PP hepatocytes; this was accompanied by a preferential PP
      increase in apoB and microsomal triglyceride transfer protein mRNA levels,
      whereas lipogenesis indicators were, if anything, similarly modified in
      hepatocytes of either acinar origin. We conclude that PP and PV hepatocytes
      exhibited similar capabilities for VLDL formation/secretion in normal conditions;
      however, the endotoxic pressure did zonate periportally.

PMID- 15716581
TI  - Effects of peroxisome proliferator-activated receptor alpha/delta agonists on HDL
      cholesterol in vervet monkeys.
AB  - The objective of this study was to demonstrate the efficacy of a novel peroxisome
      proliferator-activated receptor (PPAR) agonist and known PPARalpha and PPARdelta
      agonists to increase HDL-cholesterol (HDL-C) in the St. Kitts vervet, a nonhuman
      primate model of atherosclerosis. Four groups (n = 6) were studied and each group
      was assigned one of the following "treatments": a) vehicle only (vehicle); b) the
      PPARdelta selective agonist GW501516 (GW); c) the PPARalpha/delta agonist T913659
      (T659); and d) the PPARalpha agonist TriCor (fenofibrate). No statistically
      significant changes were seen in body weight, total plasma cholesterol, plasma
      triglycerides, VLDL-C, LDL-C, or apolipoprotein B (apoB) concentrations. Each of
      the PPARalpha and PPARdelta agonists investigated in this study increased plasma
      HDL-C, apoA-I, and apoA-II concentrations and increased HDL particle size in St.
      Kitts vervets. The maximum percentage increase in HDL-C from baseline for each
      group was as follows: vehicle, 5%; GW, 43%; T659, 43%; and fenofibrate, 20%.
      Treatment with GW and T659 resulted in an increase in medium-sized HDL particles,
      whereas fenofibrate showed increases in large HDL particles. These data provide
      additional evidence that PPARalpha and PPARdelta agonists (both mixed and
      selective) have beneficial effects on HDL-C in these experimental primates.

PMID- 15716582
TI  - Evidence for two enzymatic pathways for omega-oxidation of docosanoic acid in rat
      liver microsomes.
AB  - We studied the omega-oxidation of docosanoic acid (C22:0) in rat liver
      microsomes. C22:0 and 22-hydroxy-docosanoic acid (omega-hydroxy-C22:0) were used
      as substrates, and the reaction products were analyzed by electrospray ionization
      mass spectrometry. In the presence of NADPH, omega-oxidation of C22:0 produced
      not only the hydroxylated product, omega-hydroxy-C22:0, but also the dicarboxylic
      acid of C22:0, docosanedioic acid (C22:0-DCA). When rat liver microsomes were
      incubated with omega-hydroxy-C22:0 in the presence of either NAD+ or NADPH, C22:0
      DCA was formed readily. Formation of C22:0-DCA from either C22:0 or omega-hydroxy
      C22:0 with NADPH as cofactor was inhibited strongly by miconazole and disulfiram,
      whereas no inhibition was found with NAD+ as cofactor. Furthermore, omega
      oxidation of C22:0 was reduced significantly when molecular oxygen was depleted.
      The high sensitivity toward the more specific cytochrome P450 inhibitors
      ketoconazole and 17-octadecynoic acid suggests that hydroxylation of C22:0 and
      omega-hydroxy-C22:0 may be catalyzed by one or more cytochrome P450 hydroxylases
      belonging to the CYP4A and/or CYP4F subfamily. This study demonstrates that C22:0
      is a substrate for the omega-oxidation system in rat liver microsomes and that
      the product of the first hydroxylation step, omega-hydroxy-C22:0, may undergo
      further oxidation via two distinct pathways driven by NAD+ or NADPH.

PMID- 15716583
TI  - Continuous monitoring of cholesterol oleate hydrolysis by hormone-sensitive
      lipase and other cholesterol esterases.
AB  - Hormone-sensitive lipase (HSL) contributes importantly to the hydrolysis of
      cholesteryl ester in steroidogenic tissues, releasing the cholesterol required
      for adrenal steroidogenesis. HSL has broad substrate specificity, because it
      hydrolyzes triacylglycerols (TAGs), diacylglycerols, monoacylglycerols, and
      cholesteryl esters. In this study, we developed a specific cholesterol esterase
      assay using cholesterol oleate (CO) dispersed in phosphatidylcholine and gum
      arabic by sonication. To continuously monitor the hydrolysis of CO by HSL, we
      used the pH-stat technique. For the sake of comparison, the hydrolysis of CO
      dispersion was also tested using other cholesteryl ester-hydrolyzing enzymes. The
      specific activities measured on CO were found to be 18, 100, 27, and 3
      micromol/min/mg for HSL, cholesterol esterase from Pseudomonas species, Candida
      rugosa lipase-3, and cholesterol esterase from bovine pancreas, respectively. The
      activity of HSL on CO is approximately 4- to 5-fold higher than on long-chain
      TAGs. In contrast, with all other enzymes tested, the rates of TAG hydrolysis
      were higher than those of CO hydrolysis. The relatively higher turnover of HSL on
      CO observed in vitro adds further molecular insight on the physiological
      importance of HSL in cholesteryl ester catabolism in vivo. Thus, HSL could be
      considered more as a cholesteryl ester hydrolase than as a TAG lipase.

PMID- 15716584
TI  - Acute inhibition of hepatic beta-oxidation in APOE*3Leiden mice does not affect
      hepatic VLDL secretion or insulin sensitivity.
AB  - Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated
      with hepatic steatosis. Whether the derangements in hepatic metabolism are
      attributable to steatosis or to the increased availability of FA metabolites is
      not known. We used methyl palmoxirate (MP), an inhibitor of carnitine palmitoyl
      transferase I, to acutely inhibit hepatic FA oxidation and investigated whether
      the FAs were rerouted into VLDL secretion and whether this would affect hepatic
      glucose production. After an overnight fast, male APOE3*Leiden transgenic mice
      received an oral dose of 10 mg/kg MP. Administration of MP led to an 83%
      reduction in plasma beta-hydroxybutyrate (ketone body) levels compared with
      vehicle-treated mice (0.47 +/- 0.07 vs. 2.81 +/- 0.16 mmol/l, respectively; P <
      0.01), indicative of impaired ketogenesis. Plasma FFA levels were increased by
      32% and cholesterol and insulin levels were decreased by 17% and 50%,
      respectively, in MP-treated mice compared with controls. MP treatment led to a
      30% increase in liver triglyceride (TG) content. Surprisingly, no effect on
      hepatic VLDL-TG production was observed between the groups at 8 h after MP
      administration. In addition, the capacity of insulin to suppress endogenous
      glucose production was unaffected in MP-treated mice compared with controls. In
      conclusion, acute inhibition of FA oxidation increases hepatic lipid content but
      does not stimulate hepatic VLDL secretion or reduce insulin sensitivity.

PMID- 15716585
TI  - An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in
      hyperlipidemic mice without causing hepatic steatosis.
AB  - High levels of plasma apolipoprotein B-100 (apoB-100), the principal
      apolipoprotein of LDL, are associated with cardiovascular disease. We
      hypothesized that suppression of apoB-100 mRNA by an antisense oligonucleotide
      (ASO) would reduce LDL cholesterol (LDL-C). Because most of the plasma apoB is
      made in the liver, and antisense drugs distribute to that organ, we tested the
      effects of a mouse-specific apoB-100 ASO in several mouse models of
      hyperlipidemia, including C57BL/6 mice fed a high-fat diet, Apoe-deficient mice,
      and Ldlr-deficient mice. The lead apoB-100 antisense compound, ISIS 147764,
      reduced apoB-100 mRNA levels in the liver and serum apoB-100 levels in a dose-
      and time-dependent manner. Consistent with those findings, total cholesterol and
      LDL-C decreased by 25-55% and 40-88%, respectively. Unlike small-molecule
      inhibitors of microsomal triglyceride transfer protein, ISIS 147764 did not
      produce hepatic or intestinal steatosis and did not affect dietary fat absorption
      or elevate plasma transaminase levels. These findings, as well as those derived
      from interim phase I data with a human apoB-100 antisense drug, suggest that
      antisense inhibition of this target may be a safe and effective approach for the
      treatment of humans with hyperlipidemia.

PMID- 15716586
TI  - Lipid homeostasis and apolipoprotein E in the development and progression of
      Alzheimer's disease.
AB  - Extracellular amyloid plaques, intracellular neurofibrillary tangles, and loss of
      basal forebrain cholinergic neurons in the brains of Alzheimer's disease (AD)
      patients may be the end result of abnormalities in lipid metabolism and
      peroxidation that may be caused, or exacerbated, by beta-amyloid peptide (Abeta).
      Apolipoprotein E (apoE) is a major apolipoprotein in the brain, mediating the
      transport and clearance of lipids and Abeta. ApoE-dependent dendritic and
      synaptic regeneration may be less efficient with apoE4, and this may result in,
      or unmask, age-related neurodegenerative changes. The increased risk of AD
      associated with apoE4 may be modulated by diet, vascular risk factors, and
      genetic polymorphisms that affect the function of other transporter proteins and
      enzymes involved in brain lipid homeostasis. Diet and apoE lipoproteins influence
      membrane lipid raft composition and the properties of enzymes, transporter
      proteins, and receptors mediating Abeta production and degradation, tau
      phosphorylation, glutamate and glucose uptake, and neuronal signal transduction.
      The level and isoform of apoE may influence whether Abeta is likely to be
      metabolized or deposited. This review examines the current evidence for diet,
      lipid homeostasis, and apoE in the pathogenesis of AD. Effects on the cholinergic
      system and response to cholinesterase inhibitors by APOE allele carrier status
      are discussed briefly.

PMID- 15716588
TI  - Structural and functional properties of V156K and A158E mutants of apolipoprotein
      A-I in the lipid-free and lipid-bound states.
AB  - Val156 of apolipoprotein A-I (apoA-I) was found to be a key amino acid in the
      structure and function of high density lipoprotein (HDL) (J. Biol. Chem., 275:
      26821-26827, 2000). To determine more precisely the functions of the individual
      amino acids proximal to Val156, serial point mutants of proapoA-I, including
      V156K, D157K, and A158E, were overexpressed and purified to at least 95% purity.
      In the lipid-free state, A158E exhibited the most profound self-associative
      patterns and the least pronounced dimyristoyl phosphatidylcholine (DMPC)
      clearance activities. In the lipid-bound state, A158E formed a larger
      reconstituted HDL (rHDL) with palmitoyloleoyl phosphatidylcholine (POPC),
      approximately 120 A, whereas other mutants and the wild type (WT) formed 97 A of
      POPC-rHDL. Cross-linking analysis revealed that A158E-rHDL harbored at least four
      protein molecules in the particle, while other rHDL conformations contained only
      two protein molecules. All of the POPC-rHDL produced smaller HDL, around 78 A,
      after 24 h of incubation in the presence of low density lipoprotein at 37 degrees
      C. V156K and A158E exhibited decreased lecithin:cholesterol acyltransferase
      activation activity in the POPC-rHDL state, showing <2% of WT reactivity
      (apparent Vmax/Km). A158E also displayed markedly different properties in
      secondary structure, and its accessibility to proteolytic enzymes is different.
      These results suggest that the two amino acids in helix 6, Val156 and Ala158, are
      critical to both the structure and function of rHDL.

PMID- 15716587
TI  - Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet
      associated proteins: role of mTOR and ERK signaling.
AB  - Lipid droplet-associated proteins play an important role in adipocyte
      triglyceride (TG) metabolism. Here, we show that trans-10,cis-12 conjugated
      linoleic acid (CLA), but not cis-9,trans-11 CLA, increased lipolysis and altered
      human adipocyte lipid droplet morphology. Before this change in morphology, there
      was a rapid trans-10,cis-12 CLA-induced increase in the accumulation of perilipin
      A in the cytosol, followed by the disappearance of perilipin A protein. In
      contrast, protein levels of adipose differentiation-related protein (ADRP) were
      increased in cultures treated with trans-10,cis-12 CLA. Immunostaining revealed
      that ADRP localized to the surface of small lipid droplets, displacing perilipin.
      Intriguingly, trans-10,cis-12 CLA increased ADRP protein expression to a much
      greater extent than ADRP mRNA without affecting stability, suggesting
      translational control of ADRP. To this end, we found that trans-10,cis-12 CLA
      increased activation of the mammalian target of rapamycin/p70 S6 ribosomal
      protein kinase/S6 ribosomal protein (mTOR/p70S6K/S6) pathway. Collectively, these
      data demonstrate that the trans-10,cis-12 CLA-mediated reduction of human
      adipocyte TG content is associated with the differential localization and
      expression of lipid droplet-associated proteins. This process involves both the
      translational control of ADRP through the activation of mTOR/p70S6K/S6 signaling
      and transcriptional control of perilipin A.

PMID- 15716589
TI  - Histone deacetylase 1: a target of 9-hydroxystearic acid in the inhibition of
      cell growth in human colon cancer.
AB  - Recent studies have shown that an endogenous lipoperoxidation product, 9
      hydroxystearic acid (9-HSA), acts in colon carcinoma cells (HT29) as a growth
      inhibitor by inducing p21(WAF1) in an immediate-early, p53-independent manner and
      that p21(WAF1) is required for 9-HSA-mediated growth arrest in HT29 cells. It is
      conceivable, therefore, to hypothesize that the cytostatic effect induced by this
      agent is at least partially associated with a molecular mechanism that involves
      histone deacetylase 1 (HDAC1) inhibition, as demonstrated for sodium butyrate and
      other specific inhibitors, such as trichostatin A and hydroxamic acids. Here, we
      show that, after administration, 9-HSA causes an accumulation of hyperacetylated
      histones and strongly inhibits the activity of HDAC1. The interaction of 9-HSA
      with the catalytic site of the enzyme has been highlighted by computational
      modeling of the human HDAC1, using its homolog from the hyperthermophilic Aquifex
      aeolicus as a template. Consistent with the experimental data, we find that 9-HSA
      can bind to the active site of the protein, showing that the inhibition of the
      enzyme can be explained at the molecular level by the ligand-protein interaction.

PMID- 15716590
TI  - Differential effects of lysolipids on steroid synthesis in cells expressing
      endogenous LPA2 receptor.
AB  - Incubation of ovarian luteal cells with the bioactive lipid mediator
      lysophosphatidic acid (LPA) for 180 min abolishes gonadotropin-induced steroid
      production with no attenuation of the cyclic AMP accumulation. Treatment with the
      lysolipid also diminishes [14C]steroid production in cells preloaded with either
      [14C]cholesterol or [14C]acetate. Neither the expression of steroidogenic acute
      regulatory (StAR) protein nor in vitro steroid synthesis is affected in isolated
      mitochondrial fractions. The LPA-induced attenuation of steroid production occurs
      only in the mid-cycle corpus luteum and is associated with a transient endogenous
      expression of mRNA for the lysophosphatidic acid A2 (LPA2) receptor (with no
      concomitant changes in the expression of LPA1 receptor). Expression of LPA2 is
      accompanied by LPA-induced sphingosine-1-phosphate (S1P) production. Because
      luteal cells, in the presence of the sphingosine kinase inhibitor
      dihydrosphingosine, can overcome the inhibitory effects of LPA on steroid
      synthesis, we suggest the possible requirement of intracellular S1P production.
      Interestingly, no LPA-induced inhibition of 8Br-cAMP-stimulated progesterone
      synthesis can be detected in Leydig tumor cell line MA10 cells expressing only
      LPA2 receptor. Surprisingly, however, exogenous S1P inhibits agonist-stimulated
      progesterone in both cell types by inhibiting cyclic AMP accumulation, suggesting
      different mechanisms of action.

PMID- 15716591
TI  - Alcohol intake modulates the genetic association between HDL cholesterol and the
      PPARgamma2 Pro12Ala polymorphism.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) Pro12Ala
      polymorphism affects plasma lipids, but to what extent alcohol intake interferes
      with this association remains unknown. We randomly recruited 251 nuclear families
      (433 parents and 493 offspring) in the framework of the European Project on Genes
      in Hypertension study and genotyped 926 participants in whom all serum lipid
      variables and information on alcohol consumption were available for PPARgamma2
      Pro12Ala. Genotype-phenotype relations were assessed using generalized estimating
      equations (GEE) and a quantitative transmission disequilibrium test (QTDT). The
      Ala12 allele was more frequent in Novosibirsk (0.17) than in Cracow (0.12) and
      Mirano (0.11) (P < 0.01). Using GEE (P = 0.03) or QTDT (P = 0.007), Italian
      offspring carrying the Ala12 allele had higher serum HDL cholesterol than
      noncarriers. HDL cholesterol levels were on average 0.086 mmol/l (P = 0.001)
      higher in drinkers than in nondrinkers. Compared with Pro12 homozygotes, Ala12
      allele carriers consuming alcohol had higher serum total and HDL cholesterol,
      with the opposite trend occurring in nondrinkers. This genotype-alcohol
      interaction was independent of the type of alcoholic beverage and more pronounced
      in moderate than in heavy drinkers. We conclude that alcohol intake modulates the
      relation between the PPARgamma2 Pro12Ala and HDL cholesterol level and that,
      therefore, the Pro12Ala polymorphism, pending confirmation of our findings, might
      affect cardiovascular prognosis.

PMID- 15716592
TI  - Association of active gamma-secretase complex with lipid rafts.
AB  - Cholesterol has been implicated in the pathogenesis of Alzheimer's disease (AD).
      Although the underlying mechanisms are not yet clear, several studies have
      provided evidence for the involvement of cholesterol-rich lipid rafts in the
      production of amyloid beta peptide (Abeta), the major component of amyloid
      deposits in AD. In this regard, the gamma-secretase complex is responsible for
      the final cleavage event in the processing of beta-amyloid precursor protein
      (betaAPP), resulting in Abeta generation. The gamma-secretase complex is a
      multiprotein complex composed of presenilin, nicastrin (NCT), APH-1, and PEN-2.
      Recent reports have suggested that gamma-secretase activity is predominantly
      localized in lipid rafts, and presenilin and NCT have been reported to be
      localized in lipid rafts. In this study, various biochemical methods, including
      coimmunoprecipitation, in vitro gamma-secretase assay, and methyl-beta
      cyclodextrin (MbetaCD) treatment, are employed to demonstrate that all four
      components of the active endogenous gamma-secretase complex, including APH-1 and
      PEN-2, are associated with lipid rafts in human neuroblastoma cells (SH-SY5Y).
      Treatment with statins, 3-hydroxy-3-methylglutaryl-CoA-reductase inhibitors,
      significantly decreased the association of the gamma-secretase complex with lipid
      rafts without affecting the distribution of flotillin-1. This effect was
      partially abrogated by the addition of geranylgeraniol. These results suggest
      that both cholesterol and protein isoprenylation influence the active gamma
      secretase complex association with lipid rafts.

PMID- 15716593
TI  - Attitudes and reported practice for obesity management in Korea after
      introduction of anti-obesity agents.
AB  - This study aimed to evaluate current clinical assessments and management of
      obesity in the primary care setting in Korea since anti-obesity agents have
      become available. A questionnaire was sent to eligible primary care physicians
      selected from a national probability sample in two specialties: family physicians
      and internists. Of 939 randomly selected physicians, 452 (48.1%) replied. We
      found that 51.8% of physicians were aware of the definition of obesity, and 33.8%
      were aware of the definition of abdominal obesity proposed by Asia-Pacific
      guideline. When evaluating apparently obese patients, 50.0% of respondents
      measured body mass index (BMI) and 20.4% measured waist circumference. Fewer than
      50% of physicians measured blood glucose or lipid profiles, both of which are
      risk factors for obesity. About 47.3% of physicians prescribed an anti-obesity
      medication without allowing sufficient time for nonpharmacologic therapy to take
      effect, and 68.8% of physicians prescribed anti-obesity medications to patients
      that requested them regardless of obesity status. The majority of respondents did
      not appropriately evaluate obesity and its risk factors, and were readily
      susceptible to prescribing anti-obesity medications. Our findings suggest that
      primary care physicians in Korea need additional education on obesity and its
      management.

PMID- 15716594
TI  - Does waist indicate dyslipidemia better than BMI in Korean adult population?
AB  - Obesity is an independent and modifiable risk factor for cardiovascular disease,
      and known as a core of the metabolic syndrome. Obesity has been largely diagnosed
      based upon anthrompometric measurements like waist circumference (WC) and body
      mass index (BMI). We sought to determine associations between anthropometric
      measurements and dyslipidemia in a community adult sample composed of 1,032
      community residents (356 men, 676 women) aged 50 yr and over in Namwon, Korea.
      Blood tests for lipid profiles, including total cholesterol (TC) and HDL
      cholesterol (HDL) were performed, and dyslipidemia was defined as TC/HDL greater
      than 4. Anthropometric measurements included WC, waist-to-height ratio (WHtR),
      waist-to-hip ratio, and BMI. All anthropometric measures were categorized into
      quartiles and evaluated for associations with dyslipidemia. TC/HDL showed the
      significant associations with the anthropometric measures, independently of
      potential confounders. In women, increases of obesity indexes by quartile
      analyses showed linear increases of odds ratios for dyslipidemia (p values <0.01
      by trend test). In men, except BMI, same patterns of association were noted. WC
      and WHtR were significantly associated with dyslipidemia in Korean adult
      population. As a simple and non-invasive method for a detection of obesity and
      dyslipidemia, anthropometric measurements could be efficiently used in clinical
      and epidemiologic fields.

PMID- 15716595
TI  - Chronic hypoxia alters vasoconstrictive responses of femoral artery in the fetal
      sheep.
AB  - The purpose of this study was to determine if mild hypoxia alters the
      responsiveness to vasoactive agents in the renal and the femoral arteries in the
      fetal sheep. Ten pregnant sheep were operated under halothane anesthesia at 116
      to 124 days' gestation. A maternal tracheal catheter was placed for infusing
      compressed air (control group, n=5) or nitrogen (hypoxia group, n=5) starting on
      post operative day 6 and maintained for 5 days. Femoral and renal arteries were
      harvested from the fetus to study the constriction response to phenylephrine (PE
      10(-9) to 10(-5)mol/L). To determine the involvement of nitric oxide as a
      modulator of vessel constriction, N-nitro-L-arginine methyl ester (L-NAME) was
      used at a concentration of 10 -4 mol/L in parallel chambers. In the hypoxia
      group, maternal PaO2 significantly decreased from a base-line of 110.4+/-1.4 to
      80.5+/-1.6 (mmHg, p<0.01), fetal PaO2 significantly decreased from a baseline of
      20.9+/-0.3 to 15.5+/-0.1 (mmHg, p<0.01). Hypoxia was associated with a
      significant increase in PE maximal response in the absence (184.5+/-6.6 vs.
      146.2+/-4.3) and presence (166.9+/-6.3 vs. 145.0+/-4.5) of L-NAME, and a decrease
      in EC50 in the absence (6.0+/-1.1 vs. 27.0+/-4.1) of L-NAME of femoral arteries.
      However, there were no significant differences in PE maximal response and EC50 in
      the absence and presence of L-NAME of renal arteries. We concluded that mild
      chronic hypoxia seems to increase the fetal femoral artery response to PE, but
      not in the fetal renal artery. This observation is consistent with a
      redistribution of cardiac output away from the carcass.

PMID- 15716596
TI  - New parameters for left ventricular function in atrial fibrillation: based on the
      relationship between RR interval and performance.
AB  - This study was designed to obtain new parameters representing left ventricular
      (LV) function independent of irregular RR intervals in atrial fibrillation (AF).
      AF patients were divided into Normal (n=9) and LV Dysfunction (n=9) groups. The
      relations between LV outflow peak ejection velocity (Vpe) and preceding (RR-1) or
      prepreceding RR intervals (RR-2) were obtained using logarithmic equations, from
      which the squared correlation coefficient (r2), slope, Vpe at RR-1 or RR-2=1 sec
      (Vpe-1), and the ratio of slope to Vpe-1 (Slope/Vpe-1) were calculated. Among the
      parameters between RR-1 and Vpe, Slope/Vpe-1 was higher in LV Dysfunction group
      than in Normal group (p=0.05). When only coordinates with RR-1 from 0.6 to 1 sec
      were included, Slope/Vpe-1 (p=0.001) was higher in LV Dysfunction group than in
      Normal group. Among the parameters between RR-2 and Vpe, Slope/Vpe-1, slope, and
      r2 were different between the two groups. In multivariate analysis, Slope/Vpe-1
      between RR-2 and Vpe was only independent parameter. However, Slope/Vpe-1 between
      RR-1 and Vpe in the coordinates with RR-1 from 0.6 to 1 sec had the highest
      discriminating power. New parameters derived from the relations between RR
      intervals and LV performance might be useful to evaluate LV function
      quantitatively in AF.

PMID- 15716597
TI  - Prevalence of and risk factors for atrial fibrillation in Korean adults older
      than 40 years.
AB  - Atrial fibrillation (AF) is a common arrhythmia that is a potent independent risk
      factor for stroke. The incidence of AF increase with age and most affected people
      have underlying cardiac disease. This study aimed to describe the prevalence of
      and risk factors for AF in Korean. In this study, 14,540 adults (male
      6,573/female 7,967) > or =40 yr old received screening test for general health
      between April 2000 and December 2000. Participants answered questionnaires and
      underwent examinations that included blood pressure, electrocardiogram (ECG),
      total cholesterol, and fasting glucose. Data analysis was done by SPSS 10.0 for
      Windows. The prevalence of AF was 0.7% in people older than 40 yr and 2.1% in
      those older than 65 yr. The prevalence in men was 1.2% and women was 0.4% in
      people older than 40 yr. The prevalence in men was 3.3% and women was 1.1% in
      people older than 65 yr. Approximately 56.6% of individuals with AF are older
      than 65 yr. The prevalence of AF was higher at all age group in men than in
      women. Also, the prevalence of AF was highest in people older than 80 yr. In
      univariate analysis, male sex, old age (> or =65 yr), hypertension, diabetes
      mellitus, left ventricular hypertrophy in ECG, stroke, and cardiac disease were
      associated with an increased risk of AF. In multivariate analysis, however, risk
      factors of AF were male (odds ratio, OR 4.1; 95% confidence interval [CI] : 2.6
      to 6.5; p=0.000), old age (OR 5.3; 95% CI:3.5 to 7.9; p=0.000), and cardiac
      disease (OR 19.8; 95% CI:12.3 to 31.8; p=0.000). In this study, the most potent
      risk factors of AF was cardiac disease.

PMID- 15716598
TI  - Prognostic factors influencing infection-related mortality in patients with acute
      leukemia in Korea.
AB  - We retrospectively reviewed the medical records of 284 patients with neutropenic
      fever following chemotherapy for acute leukemia at the Catholic Hematopoietic
      Stem Cell Transplantation Center from January 1998 to December 1999, to identify
      prognostic factors for infection-related mortality. Twenty-eight patients died of
      infections. There was no difference in median age, gender ratio, or underlying
      disease between the dying and surviving groups. Bacteria were the main pathogens
      following chemotherapy, and Gram positive organisms predominated in the dying
      group. Pneumonia and sepsis were the main causes of death. There were 72 cases of
      invasive fungal infection and their mortality was 27.8%. Invasive fungal
      infection and previous history of fungal infection were independent prognostic
      factors for outcome. Recovery from neutropenia was the significant protective
      factor for mortality. In conclusion, the prognostic factors identified in this
      study could be useful for deciding on more intensive treatment for those patients
      at greater risk of death. To our knowledge, this is the first Korean study
      delineating prognostic factors in acute leukemic patients with infectious
      complications.

PMID- 15716600
TI  - Effects of particulate matter (PM10) on the pulmonary function of middle-school
      children.
AB  - It has been reported that the particulate matter under 10 microm (PM10) has
      deleterious effects on respiratory health. The purpose of this study was to
      assess the influence of PM10 upon normal children's lung function. The subjects
      were 368 middle school students in two areas of Incheon Metropolitan City. One
      (Incheon) is in the central city and the other (Ganghwa) is in the suburbs. Air
      pollution data in the vicinities of two participating schools were obtained from
      monthly report of air quality from Korean Ministry of Environment in 2000.
      Pulmonary function testing (PFT) was done two times, the first one in March and
      the second one in December with the same students. We analyzed the relationship
      between the PM10 levels and pulmonary functions (FEV1, FVC) of the children. The
      monthly average of the PM10 level between the two areas showed no significant
      difference (55.3 vs. 52.3 microg/m3). In both regions, the difference of the PM10
      level between March and December was statistically significant (64 vs. 56
      microg/m3 in Incheon, 64 vs. 54 microg/m3 in Ganghwa). The findings of the PFT
      values in March were significantly lower than those values found in December for
      both regions. In conclusion, we suggest that PM10 has some adverse effect on the
      pulmonary function of normal children.

PMID- 15716599
TI  - Molecular cytogenetic analysis of gene rearrangements in childhood acute
      lymphoblastic leukemia.
AB  - The aims of this study were to estimate the incidences of BCR/ABL, MLL, TEL/AML1
      rearrangements, and p16 deletions in childhood acute lymphoblastic leukemia
      (ALL), to identify new abnormalities, and to demonstrate the usefulness of
      interphase fluorescence in situ hybridization (FISH). We performed G-banding
      analysis and FISH using probes for BCR/ABL, MLL, TEL/AML1 rearrangements, and p16
      deletions on 65 childhood ALL patients diagnosed and uniformly treated at a
      single hospital. Gene rearrangements were identified in 73.8% of the patients
      using the combination of G-banding and FISH, while the chromosomal abnormalities
      were identified in 49.2% using G-banding alone. Gene rearrangements were
      disclosed by FISH in 24 (72.7%) of 33 patients with normal karyotype or no
      mitotic cell in G-banding. Among the gene rearrangements detected by FISH, the
      most common gene rearrangement was p16 deletion (20.3%) and the incidences of
      others were 14.1% for TEL/AML1, 11.3% for MLL, and 1.8% for BCR/ABL
      translocations. Infrequent or new aberrations such as AML1 amplification, MLL
      deletion, ABL deletion, and TEL/AML1 fusion with AML1 deletion were also
      observed. We established the rough incidences of gene rearrangements in childhood
      ALL, found new abnormalities and demonstrated the diagnostic capability of
      interphase FISH to identify cryptic chromosome aberrations.

PMID- 15716601
TI  - Occupational asthma and rhinitis induced by a herbal medicine, Wonji (Polygala
      tenuifolia).
AB  - Occupational asthma is induced by many agents, including herbal materials, that
      are exposed in working places. Although there are a few case reports for
      occupational allergy induced by herbal materials, there is none for that induced
      by Wonji (Polygala tenuifolia). This study was conducted to evaluate clinical
      characteristics and immunologic mechanism of Wonji-induced asthma in a exposed
      worker. A patient who complained of asthma and rhinitis symptoms, and who had
      worked in a herbal manufacturing factory for 8 yr, underwent a skin prick test
      with crude extract of Wonji under the impression of occupational asthma induced
      by the agent. The patient had a strong positive response to the extract on the
      skin prick test. Allergen bronchial challenge to the extract demonstrated a
      typical dual response. Serum specific IgE level to the extract was higher in the
      patient than in healthy controls, and ELISA inhibition test revealed complete
      inhibition of IgE binding with the extract, but no inhibition with Der p 2 or
      mugwort extracts. Six IgE binding components to the extract (10, 25, 28, 36, 50,
      and 90 kDa) were detected using SDS-PAGE and immunoblot analysis. These findings
      suggest that Polygala tenuifolia, a herbal material, can induce IgE-mediated
      bronchoconstriction in exposed workers.

PMID- 15716602
TI  - Expression of CD99 in pleomorphic carcinomas of the lung.
AB  - Pleomorphic carcinoma of the lung (PCL) is characterized by a mixture of
      sarcomatoid and carcinoma components, and a poor prognosis. However, no
      immunophenotype of tumor markers has been characterized in PCL. To characterize
      the immunophenotype for CD99 in PCL, we performed an immunohistochemical
      evaluation of PCLs for thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7
      and 20, and for CD99. CD99 was found to be expressed in both carcinomatous (47%)
      and sarcomatous components such as spindle cells (92%) and giant cells (57%). In
      the case of spindle cells, CK7 was expressed in 6 cases (46%) and TTF-1 in 2
      cases (15%), whereas for giant cells CK7 was expressed in 8 cases (57%) and TTF-1
      in one case (7%). However, CK20 was not expressed in either the carcinomatous or
      sarcomatous components in any case. Thus, CD99 was found to be widely expressed
      in both sarcomatous and carcinoma component in PCL. A clinicopathological
      analysis showed no direct correlation between the expression of CD99 and the
      clinical indices (stage, survival rate, invasion) of PCL.

PMID- 15716603
TI  - Expression of inducible nitric oxide synthase is increased in rat Barrett's
      esophagus induced by duodenal contents reflux.
AB  - Barrett's esophagus is a premalignant condition of esophageal adenocarcinoma.
      Inducible nitric oxide synthase (iNOS) is induced by cytokines and can generate
      locally high concentrations of nitric oxide (NO), whose metabolites can mediate
      genotoxicity and influence multistage carcinogenesis by causing DNA damage.
      Therefore, we evaluated the immunolocalization and expression of iNOS in
      surgically induced rat Barrett's esophagus. Esophagoduodenal anastomosis was
      performed in rats for inducing reflux of duodenal contents. Rats were killed at
      postoperative 10, 20, 30 and 40 weeks. We examined histologic changes and iNOS
      expression in esophagus by immunohistochemistry and reverse transcription
      polymerase chain reaction. Eighty six percent of experimental rats showed
      Barrett's esophagus above esophagoduodenal junction. iNOS immunoreactivity was
      clearly observed in the epithelial cells of Barrett's esophagus, predominantly at
      the apical surface of epithelial cells. Cytoplasmic staining was also seen only
      in atypical Barrett's esophagus. iNOS mRNA was detected only in the lower
      esophagus of experimental group. In conclusion, this study suggests that iNOS has
      some roles on Barrett's esophagus formation.

PMID- 15716604
TI  - In vitro and in vivo efficacy of new blue light emitting diode phototherapy
      compared to conventional halogen quartz phototherapy for neonatal jaundice.
AB  - High intensity light emitting diodes (LEDs) are being studied as possible light
      sources for the phototherapy of neonatal jaundice, as they can emit high
      intensity light of narrow wavelength band in the blue region of the visible light
      spectrum corresponding to the spectrum of maximal bilirubin absorption. We
      developed a prototype blue gallium nitride LED phototherapy unit with high
      intensity, and compared its efficacy to commercially used halogen quartz
      phototherapy device by measuring both in vitro and in vivo bilirubin
      photodegradation. The prototype device with two focused arrays, each with 500
      blue LEDs, generated greater irradiance than the conventional device tested. The
      LED device showed a significantly higher efficacy of bilirubin photodegradation
      than the conventional phototherapy in both in vitro experiment using
      microhematocrit tubes (44+/-7% vs. 35+/-2%) and in vivo experiment using Gunn
      rats (30+/-9% vs. 16+/-8%). We conclude that high intensity blue LED device was
      much more effective than conventional phototherapy of both in vitro and in vivo
      bilirubin photodegradation. Further studies will be necessary to prove its
      clinical efficacy.

PMID- 15716605
TI  - Lack of association between hepatitis B virus infection and polymorphism of
      mannose-binding lectin gene in Korean population.
AB  - Mannose-binding lectin (MBL) plays an important role in immune defense. This
      study was undertaken to investigate the association between hepatitis B virus
      infection and polymorphisms of MBL gene. We assessed the single nucleotide
      polymorphism at codon 54 in exon 1 of MBL in patients with hepatitis B virus
      infection and HBsAg negative controls in Korean population. A total of 498
      enrolled subjects was classified into four groups. Group 1; Clearance, Group 2;
      Inactive healthy carrier, Group 3; Chronic hepatitis, Group 4; Liver cirrhosis.
      MBL gene polymorphisms at codon 54 led to three genotypes (G/G, G/A, A/A). When
      we divided subjects into clearance group (group 1) and persistence group (group 2
      4), G/G genotype and A-allele carrier were observed in 55.6% and 44.4% in
      clearance group, 64.8% and 35.2% in persistence group (p=0.081), respectively.
      When hepatitis B virus persistent cases were divided into inactive healthy
      carrier (group 2) and disease progression group (group 3 and 4), MBL gene
      polymorphisms at codon 54 were not related to disease progression (p=0.166). MBL
      gene polymorphism at codon 54 was not associated with the clearance of hepatitis
      B virus infection nor progression of disease in chronic hepatitis B virus
      infection.

PMID- 15716606
TI  - The relation between hypoalbuminemia and compliance and intima-media thickness of
      carotid artery in continuous ambulatory peritoneal dialysis patients.
AB  - The aim of this study was to identify the main factor affecting compliance and
      intima-media thickness of the elastic common carotid artery in continuous
      ambulatory peritoneal dialysis patients. Increased intima-media thickness and
      decreased arterial compliance are associated with elevated risk of cardiovascular
      disease. This study included 20 patients and 20 age- and sex- matched healthy
      control subjects. The compliance and intima-media thickness of the right common
      carotid artery within 1 cm to the bifurcation were measured three times using
      high-resolution B-mode echocardiography. Blood samples were obtained to measure
      levels of hemoglobin, phosphorus, total calcium, total CO2, serum albumin, C
      reactive protein, serum total cholesterol, LDL- and HDL-cholesterol and
      triglycerides. We found that the compliance of common carotid artery was lower in
      the patient group than in the control group. In the patient group, the compliance
      of common carotid artery was positively correlated with serum albumin
      concentration, and intima-media thickness of common carotid artery was negatively
      correlated with serum albumin levels. Stepwise regression analysis showed that
      serum albumin concentration was independently related to the compliance of common
      carotid artery, suggesting hypoalbuminemia can independently give deleterious
      effects on the arterial wall in continuous ambulatory peritoneal dialysis
      patients.

PMID- 15716607
TI  - Clinical characteristics of renal transplant recipients that underwent urologic
      surgery for de novo disease before and after transplantation.
AB  - The pre-transplantation goal of the urologist is the optimization of urinary
      tract condition. Therefore, urologic surgery may be needed before or after renal
      transplantation. We analyzed the results of urologic surgery performed because of
      de novo urologic diseases. Between January 1986 and January 2001, 281 patients
      underwent renal transplantation, and 23 urologic surgical procedures were
      performed on 21 transplant recipients before or after renal transplantation
      because of de novo urologic diseases. By review the major reasons for urologic
      surgery in recipients were polycystic kidney diseases, vesicoureteral reflux, and
      dysfunctional voiding disorders. Nineteen surgical corrective procedures were
      done average 2.9 months before transplantation. The mortality rate was 10.5%.
      Four patients underwent urologic surgery at an average 57.5 months after
      transplantation. We highlight the fact that patients with uremia are vulnerable
      to surgical complications, and conclude that more intensive longterm urologic
      follow-ups should be conducted on recipients.

PMID- 15716608
TI  - The influence of mycophenolate mofetil and azathioprine on the same cadaveric
      donor renal transplantation.
AB  - In order to evaluate whether immunosuppressive agents such as mycophenolate
      mofetil (MMF) and azathioprine would differently influence the outcome of the
      renal transplants, we prospectively analyzed the incidence of acute rejection
      episodes, cytomegalovirus infection within the first 6 months following renal
      transplantation and 5 yr graft survival rate after minimizing influences of donor
      factors by grafting the same cadaveric donor kidney. There was no significant
      difference in sex, HLA mismatch, cold ischemic time, and patients' weight between
      the two groups. Contrary to the previous studies which demonstrated that MMF
      could lower the incidence of acute rejection episodes and improved graft survival
      rate, the two groups showed no significant difference in the incidence of acute
      rejection episodes and 5-yr graft survival rate as well. This discrepancy in
      these results might explain that donor factors could be important to cadaveric
      renal transplantation. Thus, we suggest that the influences of donor factors
      should be considered in further clinical studies of cadaveric renal
      transplantation.

PMID- 15716609
TI  - Gene expression analysis of cultured amniotic fluid cell with Down syndrome by
      DNA microarray.
AB  - Complete or partial triplication of human chromosome 21 results in Down syndrome
      (DS). To analyze differential gene expressions in amniotic fluid (AF) cells of
      DS, we used a DNA microarray system to analyze 102 genes, which included 24 genes
      on chromosome 21, 28 genes related to the function of brain and muscle, 36 genes
      related to apoptosis, 4 genes related to extracellular matrix, 8 genes related to
      other molecular function and 2 house-keeping genes. AF cells were collected from
      12 pregnancies at 16-18 weeks of gestation in DS (n=6) and normal (n=6) subjects.
      Our DNA microarray experiments showed that the expressions of 11 genes were
      altered by at least 2-folds in DS, as follows. Ten genes, COL6A1, CASP5, AKT2,
      JUN, PYGM, BNIP1, OSF-2, PRSS7, COL3A1, and MBLL were down-regulated and GSTT1
      was only up-regulated. The differential expressions of GSTT1 and COL3A1 were
      further confirmed by semi-quantitative RT-PCR for each sample. The gene dosage
      hypothesis on chromosome 21 may explain the neurological and other symptoms of
      DS. However, our results showed that only two genes (COL6A1 and PRSS7), among 24
      genes on chromosome 21, were down-regulated in the AF cells of DS. Our data may
      provide the basis for a more systematic identification of biological markers of
      fetal DS, thus leading to an improved understanding of pathogenesis for fetal DS.

PMID- 15716610
TI  - Effect of antenatal corticosteroid and antibiotics in pregnancies complicated by
      premature rupture of membranes between 24 and 28 weeks of gestation.
AB  - The aim of this study was to assess the effectiveness of active intervention with
      antenatal maternal corticosteroid and antibiotics therapy in infants delivered
      between 24 and 28 weeks of gestation after premature rupture of membrane. This
      retrospective study included pregnant women complicated by preterm delivery at
      the Dong-A University Hospital from 1998 to 2002. Patients were divided into
      labor induction group 1 (n=20), observation group 2 (n=19), and medication group
      3 (n=20). We evaluated the effects of prolongation of pregnancy and intervention
      with maternal corticosteroids and antibiotics therapy on perinatal and neonatal
      outcomes. Each group did not have a significant difference (p<0.05) in neonatal
      outcomes, such as respiratory distress syndrome, intraventricular hemorrhage,
      necrotizing enterocolitis, retinopathy of prematurity, pneumonia,
      bronchopulmonary dysplasia, and sepsis. The mean latency period was 4.7 days and
      7.6 days in groups 2 and 3, respectively. Therefore, this study was unable to
      demonstrate any beneficial effects of corticosteroids in improving neonatal
      outcomes and prolongation of the latency period with antibiotics.

PMID- 15716611
TI  - Cytologic findings of cervicovaginal smears in women with uterine papillary
      serous carcinoma.
AB  - The goal of this study was to evaluate the cytomorphologic features of
      histologically confirmed uterine papillary serous carcinomas (UPSC) of the
      endometrium. We reviewed cervicovaginal smears from 12 patients with UPSC who had
      done their cervical smears at six months to a year earlier before the time of
      diagnosis; nine smears (75%) were diagnosed as positive for malignancy and three
      smears (25%) were diagnosed as negative. The cervical smears of patients with
      UPSC revealed frequent papillary clusters that were composed of large pleomorphic
      tumor cells with prominent nucleoli in a background of necrosis. Other findings
      revealed from the tests were relatively frequent single malignant cells and bare
      nuclei. Although the Pap smear is not a sensitive screening test for endometrial
      carcinoma, we could depend on it to reveal the cytologic features of UPSC which
      are fairly characteristic and reliable for a preoperative diagnosis of UPSC.
      Preoperative identification of this poor prognostic variant of endometrial
      carcinoma may influence the surgical management of these cases and the choice of
      adjuvant therapy.

PMID- 15716613
TI  - A study of skin color by melanin index according to site, gestational age, birth
      weight and season of birth in Korean neonates.
AB  - Human skin color shows variations throughout life and influenced by various
      factors such as race, sex, age and hormones. Since the development of
      spectrophotometer, many studies on human skin color have been done. However, few
      studies have been carried out to measure the skin color of neonatal infants. The
      aim of our study was to assess the variations in skin color according to site,
      gestational age, birth weight and season of birth in Korean neonates. A total of
      447 healthy neonates (3 days after birth, 213 males and 234 females) were
      enrolled in the present study. Skin pigmentation was measured by reflectance
      spectrophotometer (Derma-Spectrophotometer, Cortex technology, Hadsund, Denmark)
      at four different sites (forehead, upper arm, abdomen, and inguinal area). The
      forehead showed highest melanin index in all sites measured (p<0.05). There was
      no significant difference according to gestational age, birth weight, and season
      of birth. This result imply that the skin color in neonates is mainly determined
      genetically.

PMID- 15716612
TI  - RET/PTC and CK19 expression in papillary thyroid carcinoma and its
      clinicopathologic correlation.
AB  - Recently, the rearrangement of RET proto-oncogene has been reported to be the
      most common genetic change in papillary thyroid carcinoma (PTC). However, its
      prevalence has been reported variably and its relation to clinical outcome has
      been controversial. The characteristic nuclear features of PTC usually render the
      diagnosis, but problem arises with equivocal cytologic features that are present
      focally. Although there remains some controversy, CK19 has been reported to be a
      useful ancillary tool for diagnosis of PTC. To evaluate the expression rate of
      RET/PTC rearrangement and CK19 in PTCs in a Korean population, we studied 115
      papillary thyroid carcinomas in 3 mm-core tissue microarray based
      immunohistochemical analysis. The prevalence of Ret protein expression was 62.6%
      and the CK19 immunoreactivity was 80.9%. There was no statistically significant
      association between the Ret positivity and CK19 immunoreactivity, although the
      percent agreement of the two was relatively high. The clinicopathological
      variables did not correlate with the expression of Ret. In conclusion, the
      prevalence of Ret protein expression and its clinicopathological implications in
      a Korean population are not much different from those reported in previous
      studies. However, its detection via immunohistochemistry can be a useful
      diagnostic tool for diagnosing papillary thyroid carcinoma in conjunction with
      CK19.

PMID- 15716614
TI  - Correlation between ultrasonographic findings and the response to corticosteroid
      injection in pes anserinus tendinobursitis syndrome in knee osteoarthritis
      patients.
AB  - The objectives of this study were to assess the ultrasonographic (US) findings in
      patients with knee osteoarthritis (OA) with pes anserinus tendinitis or bursitis
      (PATB) syndrome and to determine the correlation between the US findings and the
      response to local corticosteroid injection. We prospectively studied 26 patients
      with knee OA with clinically diagnosed PATB syndrome. A linear array 7 MHz
      transducer was used for US examination of the knee. Seventeen patients were
      injected locally with tramcinolone acetonide in the anserine bursa area. Response
      to local corticosteroid injection was evaluated by pain visual analog scale
      (VAS), Western Ontario and MacMaster (WOMAC) osteoarthritis index and Global
      patient/physician assessment using Likert scale. On US examination, only 2
      patients (8.7%) showed evidence of PATB. Pain VAS, WOMAC pain index and WOMAC
      physical function index improved significantly after corticosteroid injection.
      Global patient assessment revealed that 2 patients showed best response, 6 good,
      1 fair, 8 the same, and none worse. It is of note that the 2 patients who showed
      the best response were those who showed US evidence of PATB. This finding shows
      that US can serve as a useful diagnostic tool for guiding treatment in PATB
      syndrome of OA patients.

PMID- 15716615
TI  - Effect of ketamine on apoptosis by energy deprivation in astroglioma cells using
      flow cytometry system.
AB  - Apoptosis is a programmed, physiologic mode of cell death that plays an important
      role in tissue homeostasis. As for the central nervous system, ischemic insults
      can induce pathophysiologic cascade of apoptosis in neurophils. Impairment of
      astrocyte functions during brain ischemia can critically influence neuron
      survival by neuronglia interactions. We aimed to elucidate the protective effect
      of ketamine on apoptosis by energy deprivation in astrocytes. Ischemic insults
      was induced with iodoacetate/ carbonylcyanide m-chlorophenylhydrazone (IAA/CCCP)
      1.5 mM/20 microm or 150 microm/2 microm for 1 hr in the HTB-15 and CRL-1690
      astrocytoma cells. Then these cells were reperfused with normal media or ketamine
      (0.1 mM) containing media for 1 hr or 24 hr. FITC-annexin-V staining and
      propidium iodide binding were determined by using flow cytometry. Cell size and
      granularity were measured by forward and side light scattering properties of flow
      cytometry system, respectively. An addition of ketamine during reperfusion
      increased the proportion of viable cells. Ketamine alleviated cell shrinkage and
      increased granularity during the early period, and ameliorated cell swelling
      during the late reperfusion period. Ketamine may have a valuable effect on
      amelioration of early and late apoptosis in the astrocytoma cells, even though
      the exact mechanism remains to be verified.

PMID- 15716616
TI  - Screening of brain metastasis with limited magnetic resonance imaging (MRI):
      clinical implications of using limited brain MRI during initial staging for non
      small cell lung cancer patients.
AB  - The purpose of this prospective study was to determine whether using magnetic
      resonance imaging (MRI) for early screening for brain metastases (BM) can improve
      quality of life, survival in patients with non-small cell lung cancer (NSCLC).
      The study group comprised 183 patients newly diagnosed with NSCLC. All patients
      underwent limited brain MRI and routine workups. The control group comprised 131
      patients with NSCLC who underwent limited brain MRI only if they had neurologic
      symptoms. The incidence of BM was 20.8% (38/183) in the study group and 4.6%
      (6/131) in the control group. The rate of upstaging based on the MRI data was
      13.5% (15/111) overall and 15.9% (11/69) in patients that had been considered
      initially to be resectable surgically. There was no significant difference in
      survival outcome between the groups. Patients who had BM alone had a greater
      overall survival time (49 weeks) than those who had multiple systemic metastases
      (27 weeks; p=0.0307). In conclusions, limited brain MRI appears to be a useful,
      cost-effective method to screen for BM at the time of initial staging. And it may
      facilitate timely treatment of patients with NSCLC and improve their survival and
      quality of life.

PMID- 15716617
TI  - Treatment duration and cost of work-related low back pain in Korea.
AB  - The purpose of this study is to present the information on the duration of
      treatment and the cost of work-related low back pain. Using the compensation
      database for 1997 work-related low back pain (n=9,277), this study estimated the
      duration of treatment, the cost of work-related low back pain, the relationship
      between them, and probability of being off treatment at different intervals. The
      mean and the median of the treatment duration are 252.6 days and 175 days. The
      mean and the median of the cost of total insurance benefit are 37,700,000 won and
      14,400,000 won. The treatment duration of 51% of the study subjects was less than
      6 months and their cost accounted for 10.2% of the total insurance benefit. The
      subjects who were treated more than 24 months were 5.8% but it accounted for
      29.2% of the cost. It was found that approximately 50% of the subjects who will
      remain on treatment at the end of n months would be off treatment at the end of
      n+5 months. This study presents the point in time when the low back pain (LBP)
      workers need to prepare to return to work by forecasting their off-treatment
      period. From the treat duration and cost perspectives, this study may be utilized
      as evidence for active management of work-related LBP.

PMID- 15716618
TI  - Effects of methylprednisolone on the neural conduction of the motor evoked
      potentials in spinal cord injured rats.
AB  - Methylprednisolone(MP), a glucocorticoid steroid, has an anti-inflammatory action
      and seems to inhibit the formation of oxygen free radicals produced during lipid
      peroxidation in a spinal cord injury(SCI). However, the effects of MP on the
      functional recovery after a SCI is controversial. The present study was conducted
      to determine the effects of MP on the recovery of neural conduction following a
      SCI. A SCI was produced using the NYU spinal cord impactor. A behavioral test was
      conducted to measure neurological disorders, and motor evoked potentials (MEPs)
      were recorded. According to the behavioral test, using BBB locomotor scaling, MP
      treated animals showed improved functional recoveries when compared to saline
      treated animals. MEP latencies in the MP-treated group were shortened when
      compared to those in the control group. Peak amplitudes of MEPs were larger in
      the MP-treated group than those in the control group. The thresholds of MEPs
      tended to be lower in the MP-treated group than those in the control group. These
      results suggest that MP may improve functional recovery after a SCI.

PMID- 15716619
TI  - A case of melioidosis presenting as migrating pulmonary infiltration: the first
      case in Korea.
AB  - Melioidosis is an infection of the Gram-negative bacterium Burkholderia
      pseudomallei. While it is known as an important cause of sepsis or chronic
      abscess-forming disease in Southeast Asia and northern Australia, no case has yet
      been reported in Korea. A 50-yr-old man visited our hospital for intermittent
      fever associated with dry cough and sputum. Roentgenographic examination showed
      migrating pulmonary infiltration. Symptoms and chest radiograph and computed
      tomography (CT) image findings did not improve despite use of fluoroquinolone
      antibiotics. Gram-negative bacteria were isolated on bronchoscopic washing
      culture and were identified as B. pseudomallei on DNA sequencing of 16S ribosomal
      RNA with 100% homology. Treatment for melioidosis was commenced with high dose
      ceftazidime, and the patient's fever, cough, and sputum were improved and the
      lesion on chest radiograph and CT almost disappeared.

PMID- 15716620
TI  - A case of pneumonia caused by Ewingella americana in a patient with chronic renal
      failure.
AB  - Though the pathogenic significance and the reservoir of Ewingella americana have
      not been clarified, this organism has caused several pathogenic infections,
      especially in immunocompromised patients. We report a pneumonia in a patient with
      chronic renal failure, who had chronic rejection of transplanted kidney. E.
      americana was identified to be the pathogen of pneumonia with clinical symptoms
      and signs and radiological examination. As soon as he was treated with
      ceftriaxone and isepamicin, clinical improvement was followed with no further
      growth of E. americana or other pathogenic isolates from sputum culture. This
      suggests to be the case of pneumonia caused by E. americana for the first time in
      the Korean literature.

PMID- 15716621
TI  - Collagenous gastritis in a Korean child: a case report.
AB  - Collagenous gastritis, a counterpart of collagenous colitis, is an extremely rare
      disorder. The first case of collagenous gastritis in a Korean boy in his pre
      teens who had been receiving treatment for refractory iron deficiency anemia has
      been reported. The patient had been suffering from intermittent abdominal pain,
      recurrent blood-tinged vomiting and poor oral intake. The gastric endoscopy
      revealed diffuse cobblestone appearance of the mucosa with easy touch bleeding
      throughout the stomach but no abnormalities in the esophagus, duodenum, and
      colon. Pathologic examination of the gastric biopsies from the antrum, body and
      cardia showed a subepithelial collagen deposition with entrapped dilated
      capillaries, moderate infiltrates of lympho-plasma cells and eosinophils of the
      lamina propria, and marked hypertrophy of the muscularis mucosa. The collagen
      deposition appeared as discontinuous bands with focally irregular extension into
      the deeper part of the antral mucosa. It measured up to 150 microm. Helicobacter
      pylori infection was not detected. The biopsies from the duodenum, esophagus and
      colon revealed no pathologic abnormalities.

PMID- 15716622
TI  - Neostigmine for the treatment of acute hepatic encephalopathy with acute
      intestinal pseudo-obstruction in a cirrhotic patient.
AB  - We treated a 49-yr-old man with neostigmine, who had liver cirrhosis, acute
      hepatic encephalopathy, and acute intestinal pseudoobstruction. He was admitted
      in a state of hepatic confusion. On physical examination, the abdomen was
      distended; and bowel sound was absent. Plain abdomen film revealed multiple air
      fluid levels and distention of bowel loops. Initially, we gave him lactulose
      enemas every 6 hr for one day without improvement in his mental state.
      Furthermore, he became to a state of coma. Therefore, we gave him 0.5 mg of
      neostigmine subcutaneously to improve his peristaltic movement, and 2 L of
      polyethylene glycol electrolyte solution through a nasogastric tube for 4 hr to
      reduce the production and absorption of gut-derived toxins of nitrogenous
      compounds. After these treatments, the venous ammonia level decreased to the
      normal range within 12 hr, and the coma disappeared after 2 days. We suggest that
      neostigmine may be one of the most effective treatments to initiate peristaltic
      movement and bowel cleansing in cirrhotic patients with acute hepatic
      encephalopathy and acute intestinal pseudoobstruction.

PMID- 15716623
TI  - Cystic fibrosis in Korean children:a case report identified by a quantitative
      pilocarpine iontophoresis sweat test and genetic analysis.
AB  - Cystic fibrosis (CF) is inherited as an autosomal recessive trait, and the
      mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene
      contributes to the CF syndrome. Although CF is common in Caucasians, it is known
      to be rare in Asians. Recently, we experienced two cases of CF in Korean
      children. The patients were girls with chronic productive cough since early
      infancy. Chest computed tomography showed the diffuse bronchiectasis in both
      lungs, and their diagnosis was confirmed by the repeated analysis of a
      quantitative pilocarpine iontophoresis test (QPIT). The sweat chloride
      concentrations of the first patient were 108.1 mM/L and 96.7 mM/L. The genetic
      analysis revealed that she was the compound heterozygote of Q1291X and IVS8 T5
      M470V. In the second case, the sweat chloride concentrations were 95.0 mM/L and
      77.5 mM/L. Although we performed a comprehensive search for the coding regions
      and exon-intron splicing junctions of CFTR gene, no obvious disease-related
      mutations were detected in the second case. To our knowledge, this is the first
      report of CF in Korean children identified by a QPIT and genetic analysis. The
      possibility of CF should be suspected in those patients with chronic respiratory
      symptoms even in Korea.

PMID- 15716624
TI  - Humerus varus in a patient with pseudohypoparathyroidism.
AB  - A 7-yr-old girl presented with progressive shortening of the right upper arm and
      limitation of shoulder motion. Pseudohypoparathyroidism associated with
      Albright's hereditary osteodystrophy was diagnosed by biochemical, hormonal and
      radiographic studies. Her condition was complicated by severe humerus varus on
      the right side. Proximal humeral valgization osteotomy and concomitant humeral
      lengthening resulted in an improvement of the shoulder joint motion and activity
      in daily life.

PMID- 15716626
TI  - Spontaneous intracerebral hematoma from transient occult carotid-cavernous
      fistula: a case report.
AB  - After the spontaneous relief of initial symptoms by traumatic carotid-cavernous
      fistula (CCF), paradoxical worsening of patient's condition can be followed. We
      present a case of a 60-yr-old man whose audible bruit from a traumatic CCF had
      completely disappeared. A few days later, however, the patient had spontaneous
      intracerebral hematoma with cortical venous drainage. Complete obliteration of
      the fistula was achieved after embolization. When initial audible bruit in
      traumatic CCF disappears suddenly, cerebral angiography should be performed to
      differentiate venous hypertension by the hemodynamic changes of the cavernous
      sinus channels from spontaneous resolution of CCF.

PMID- 15716625
TI  - A Korean family of hypokalemic periodic paralysis with mutation in a voltage
      gated calcium channel (R1239G).
AB  - Hypokalemic periodic paralysis (HOPP) is a rare disease characterized by
      reversible attacks of muscle weakness accompanied by episodic hypokalemia. Recent
      molecular work has revealed that the majority of familial HOPP is due to
      mutations in a skeletal muscle voltage-dependent calcium-channel: the
      dihydropyridine receptor. We report a 13-yr old boy with HOPP from a family in
      which 6 members are affected in three generations. Genetic examination identified
      a nucleotide 3705 C to G mutation in exon 30 of the calcium channel gene,
      CACNA1S. This mutation predicts a codon change from arginine to glycine at the
      amino acid position #1239 (R1239G). Among the three known mutations of the
      CACNA1S gene, the R1239G mutation was rarely reported. This boy and the other
      family members who did not respond to acetazolamide, showed a marked improvement
      of the paralytic symptoms after spironolactone treatment.

PMID- 15716627
TI  - Cervical spinal cord injury upregulates ventral spinal 5-HT2A receptors.
AB  - Following chronic C2 spinal hemisection (C2HS), crossed spinal pathways to
      phrenic motoneurons exhibit a slow, spontaneous increase in efficacy by a
      serotonin (5-HT)-dependent mechanism associated with 5-HT2A receptor activation.
      Further, the spontaneous appearance of cross-phrenic activity following C2HS is
      accelerated and enhanced by exposure to chronic intermittent hypoxia (CIH). We
      hypothesized that chronic C2HS would increase 5-HT and 5-HT2A receptor expression
      in ventral cervical spinal segments containing phrenic motoneurons. In addition,
      we hypothesized that CIH exposure would further increase 5-HT and 5-HT2A receptor
      density in this region. Control, sham-operated, and C2HS Sprague-Dawley rats were
      studied following normoxia or CIH (11% O2-air; 5-min intervals; nights 7-14 post
      surgery). At 2 weeks post-surgery, ventral spinal gray matter extending from C4
      and C5 was isolated ipsilateral and contralateral to C2HS. Neither C2HS nor CIH
      altered 5-HT concentration measured with an ELISA on either side of the spinal
      cord. However, 5-HT2A receptor expression assessed with immunoblots increased in
      ipsilateral gray matter following C2HS, an effect independent of CIH.
      Immunocytochemistry revealed increased 5-HT2A receptor expression on identified
      phrenic motoneurons (p<0.05), as well as in the surrounding gray matter.
      Contralateral to injury, 5-HT2A receptor expression was elevated in CIH, but not
      normoxic C2HS rats (p<0.05). Our data are consistent with the hypothesis that
      spontaneous increase in 5-HT2A receptor expression on or near phrenic motoneurons
      contributes to strengthened crossed-spinal synaptic pathways to phrenic
      motoneurons following C2HS.

PMID- 15716628
TI  - The assessment of locomotor function in spinal cord injured rats: the importance
      of objective analysis of coordination.
AB  - The Basso, Beattie and Bresnahan (BBB) locomotor rating scale is the most widely
      used open field test and has been accepted as a valid way to assess locomotor
      function after spinal cord contusion injury in the rat. A limitation within the
      BBB locomotor rating scale is the correct assessment of forelimb (FL)-hindlimb
      (HL) coordination. This limitation can have major implications for the final
      assessment of locomotor function. In the present study, we show an objective
      method to assess coordination based on the regularity index (RI), achieved
      through the use of the CatWalk method. The RI grades the degree of coordination
      as the result of the number of normal step sequence patterns multiplied by four
      and divided by the total amount of paw placements. Using the RI, single walkway
      crossings can be objectively analyzed on coordination. Integration of the CatWalk
      based coordination into the BBB scale indicates that objective analysis of
      coordination results in reliable and more sensitive assessment of locomotor
      function. This new method has been tested successfully in determination of
      positive effects of enriched housing on functional recovery after spinal cord
      injury (SCI).

PMID- 15716629
TI  - Chondroitinase ABCI improves locomotion and bladder function following contusion
      injury of the rat spinal cord.
AB  - Chondroitin sulfate proteoglycans are synthesized and deposited in the spinal
      cord following injury. These proteoglycans may restrict regeneration and
      plasticity and contribute to the limited recovery seen after an injury.
      Chondroitinase, a bacterial enzyme that catalyzes the hydrolysis of the
      chondroitin chains on proteoglycans, has been shown to improve motor and sensory
      function following partial transection lesions of the spinal cord. To assess the
      effects of chondroitinase in a clinically relevant model of spinal cord injury,
      128 female Long-Evans rats received either a severe, moderate, or mild contusion
      injury at the vertebral level T9/T10 with a forceps model and were treated for 2
      weeks with chondroitinase ABCI at 0.06 Units per dose, penicillinase, or vehicle
      control via an intrathecal catheter placed near the injury. Motor behavior was
      measured by open-field testing of locomotion and bladder function monitored by
      measuring daily residual urine volumes. Animals treated with chondroitinase
      showed significant improvements in open-field locomotor activity as measured by
      the Basso, Beattie and Bresnahan scoring system after both severe and moderate
      SCI (p<0.05 and 0.01, respectively). No significant locomotor differences were
      observed in the mild injury group. In the moderate injury group, residual urine
      volumes were reduced with chondroitinase treatment by 2 weeks after injury
      (p<0.05) and in the severe injury group, by 6 weeks after injury (NS). These
      results demonstrate that chondroitinase is effective at promoting both somatic
      and autonomic motor recovery following a clinically relevant contusion spinal
      cord injury and is a candidate as a therapeutic for human spinal cord injury.

PMID- 15716630
TI  - Nicotine attenuates morphological deficits in a contusion model of spinal cord
      injury.
AB  - Protection against the progression of secondary injury appears to be an effective
      therapeutic strategy in spinal cord injury (SCI). Evidence indicates that
      nicotine can induce potent neuroprotective effects against injury to spinal cord
      neurons. Therefore, the present study was focused on the effects of nicotine on
      the behavioral and morphological recovery associated with SCI. Adult male Long
      Evans rats were subjected to a moderate contusion model of SCI and received
      subcutaneous injections of nicotine for 14 days at the dose of 0.35 or 7
      mg/kg/day. The rats were examined using the BBB locomotor rating scale for 6
      weeks. At the end of the BBB recording, spinal cords were examined for the
      volumetric tissue sparing of gray and white matters. All SCI rats demonstrated a
      loss of hindlimb function followed by a recovery phase that peaked at 2-3 weeks
      after the trauma. Compared to untreated SCI rats, chronic nicotine administration
      appeared to improve the recovery of the locomotor functions. Indeed, nicotine
      treated animals scored consistently higher on the BBB scale indicating that the
      treatment altered animal behavior. However, when taking under consideration
      correction factors for multiple comparisons, these data did not reach
      significance at overall experimental levels of significance 0.05. Nevertheless,
      nicotine administration was effective in sparing tissue at injury epicenter and a
      lower dose of nicotine also resulted in significant sparing of white matter of
      the injured spinal cord. These results suggest that agonists of neuronal
      nicotinic receptors can be attractive candidates for SCI therapy.

PMID- 15716631
TI  - Spatial and temporal characteristics of neurodegeneration after controlled
      cortical impact in mice: more than a focal brain injury.
AB  - The present study examined the neuropathology of the lateral controlled cortical
      impact (CCI) traumatic brain injury (TBI) model in mice utilizing the de Olmos
      silver staining method that selectively identifies degenerating neurons and their
      processes. The time course of ipsilateral and contralateral neurodegeneration was
      assessed at 6, 24, 48, 72, and 168 h after a severe (1.0 mm, 3.5 M/sec) injury in
      young adult CF-1 mice. At 6 hrs, neurodegeneration was apparent in all layers of
      the ipsilateral cortex at the epicenter of the injury. A low level of
      degeneration was also detected within the outer molecular layer of the underlying
      hippocampal dentate gyrus and to the mossy fiber projections in the CA3 pyramidal
      subregions. A time-dependent increase in cortical and hippocampal
      neurodegeneration was observed between 6 and 72 hrs post-injury. At 24 h,
      neurodegeneration was apparent in the CA1 and CA3 pyramidal and dentate gyral
      granule neurons and in the dorsolateral portions of the thalamus. Image analysis
      disclosed that the overall volume of ipsilateral silver staining was maximal at
      48 h. In the case of the hippocampus, staining was generalized at 48 and 72 h,
      indicative of damage to all of the major afferent pathways: perforant path, mossy
      fibers and Schaffer collaterals as well as the efferent CA1 pyramidal axons. The
      hippocampal neurodegeneration was preceded by a significant increase in the
      levels of calpain-mediated breakdown products of the cytoskeletal protein alpha
      spectrin that began at 6 h, and persisted out to 72 h post-injury. Damage to the
      corpus callosal fibers was observed as early as 24 h. An anterior to posterior
      examination of neurodegeneration showed that the cortical damage included the
      visual cortex. At 168 h (7 days), neurodegeneration in the ipsilateral cortex and
      hippocampus had largely abated except for ongoing staining in the cortical areas
      surrounding the contusion lesion and in hippocampal mossy fiber projections.
      Callosal and thalamic neurodegeneration was also very intense. This more complete
      neuropathological examination of the CCI model shows that the associated damage
      is much more widespread than previously appreciated. The extent of ipsilateral
      and contralateral neurodegeneration provides a more complete anatomical correlate
      for the cognitive and motor dysfunction seen in this paradigm and suggests that
      visual disturbances are also likely to be involved in the post-CCI neurological
      deficits.

PMID- 15716632
TI  - NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage
      following lateral fluid percussion TBI in rats.
AB  - Traumatic brain injury (TBI) produces a rapid and excessive elevation in
      extracellular glutamate associated with excitotoxicity and secondary brain
      pathology. The peptide neurotransmitter Nacetylaspartylglutamate (NAAG)
      suppresses glutamate transmission through selective activation of presynaptic
      Group II metabotropic glutamate receptor subtype 3 (mGluR3). Thus, inhibition of
      NAAG peptidase activity and the prolong presence of synaptic NAAG were
      hypothesized to have significant potential for cellular protection following TBI.
      In the present study, a novel NAAG peptidase inhibitor, ZJ-43, was used in four
      different doses (0, 50, 100, or 150 mg/kg). Each dose was repeatedly administered
      i.p. (n=5/group) by multiple injections at three times (0 time, 8 h, 16 h) after
      moderate lateral fluid percussion TBI in the rat. An additional group was co
      administered ZJ-43 (150 mg/kg) and the Group II mGluR antagonist, LY341495 (1
      mg/kg), which was predicted to abolish any protective effects of ZJ-43. Rats were
      euthanized at 24 h after TBI, and brains were processed with a selective marker
      for degenerating neurons (Fluoro-Jade B) and a marker for astrocytes (GFAP).
      Ipsilateral neuronal degeneration and bilateral astrocyte loss in the CA2/3
      regions of the hippocampus were quantified using stereological techniques.
      Compared with vehicle, ZJ-43 significantly reduced the number of the ipsilateral
      degenerating neurons (p<0.01) with the greatest neuroprotection at the 50 mg/kg
      dose. Moreover, LY341495 successfully abolished the protective effects of ZJ-43.
      50 mg/kg of ZJ-43 also significantly reduced the ipsilateral astrocyte loss
      (p<0.05). We conclude that the NAAG peptidase inhibitor ZJ-43 is a potential
      novel strategy to reduce both neuronal and astrocyte damage associated with the
      glutamate excitotoxicity after TBI.

PMID- 15716633
TI  - Spreading depression expands traumatic injury in neocortical brain slices.
AB  - Traumatic brain injury (TBI) is particularly common in young people, generating
      healthcare costs that can span decades. The cellular processes activated in the
      first minutes following injury are poorly understood, and the 3-4 h following
      trauma are crucial for reducing subsequent injury. Spreading depression (SD) is a
      profound inactivation of neurons and glia lasting 1-2 min that arises focally and
      migrates outward across gray matter. In the hours following focal stroke, the
      metabolic stress of energy reduction and recurring SD-like events (peri-infarct
      depolarizations, PIDs) interact to promote neuronal injury. Similar recurring
      depolarizations might evolve immediately following TBI and exacerbate neuronal
      damage peripheral to the impact site. To test this possibility and examine if
      certain drugs might limit damage by inhibiting what we term traumatic spreading
      depression (tSD), we developed a technique whereby a small weight was dropped
      onto a live slice of rat neocortex while imaging changes in light transmittance
      (LT). Imaging revealed a propagating front of increased LT arising at the border
      of the impact site. Traumatic SD significantly expanded the region of ensuing
      damage. Both tSD and subsequent damage were blocked by the NMDA receptor
      antagonist MK-801 (100 microM) or the sigma-1 receptor (sigma1R) ligands
      dextromethorphan (30 microM) or BD-1063 (100 microM). Co-application of the
      sigma1R antagonist (+)3-PPP with DM reversed the block as did lowering
      temperature from 35 degrees C to 32 degrees C. This study provides evidence that
      an event similar to peri-infarct depolarization can arise from an injury site in
      neocortex within seconds following impact and act to expand the region of acute
      neuronal damage.

PMID- 15716634
TI  - Thrombocytopenia predicts progressive hemorrhage after head trauma.
AB  - Patients with traumatic brain injury (TBI) often show progression of hemorrhagic
      injuries (PHI) after admission to the hospital. This progression is correlated
      with poor outcome. In this study, we have investigated if thrombocytopenia was a
      risk factor for PHI. The study was performed on patients admitted to the hospital
      with severe TBI during year 2000. In total, 50 patients were admitted with severe
      TBI. Twenty-seven out of these had complete platelet counts at admission and 24
      hours thereafter and were included for further study. We found thrombocytopenia
      at admission to be a risk factor for PHI (p=0.008). We also found that the
      platelet count decreased more significantly during the first 24 h after injury in
      patients with PHI compared to patients without PHI (p=0.009). A trend towards
      longer periods of mechanical ventilation in patients with PHI compared to
      patients without PHI was identified. These findings support a causal relationship
      between thrombocytopenia and PHI. The findings provide a rationale for future
      studies of hemostatic agents in the treatment of TBI in order to minimise
      complications caused by PHI.

PMID- 15716635
TI  - Abnormal motor preparation in severe traumatic brain injury with good recovery.
AB  - Movement-related cortical potentials (MRCPs) were examined in seven patients with
      severe traumatic brain injury (TBI) and 12 matched control subjects. All patients
      had clinically established good recovery by the time of testing. Flexion
      movements of the index finger of the left or right hand were recorded in two
      (alternating and repetitive) self-paced conditions and in one externally
      triggered condition. In control subjects, the bereitschaftspotential (BP)
      component of MRCP was detected approximately 2000 msec prior to movement onset in
      the self-paced conditions and was larger and earlier in the alternating compared
      to the repetitive condition. The BP component was absent in the externally
      triggered condition. In TBI patients, the BP was greatly reduced and no
      difference between the alternating-repetitive conditions was detected; in
      contrast, only small differences were present in the controls for the negative
      slope (NS) and MP components and no difference for the reafferent positivity
      (RAP) component. A dipole analysis indicated the supplementary motor area and the
      premotor area as the likely generators of BP and NS' components, respectively.
      Gradientrecalled echo magnetic resonance imaging allowed the detection of a
      number of small hypointense lesions primarily located in the frontal lobes, as in
      diffuse axonal injury. This pattern of results indicates a selective deficit in
      motor preparation and a relatively spared pattern of activation during and
      following movement in these patients. Imaging data appear generally consistent
      with the pattern of MRCPs observed in the patient group. Implications of these
      results for the problem of slowness in TBI patients are discussed.

PMID- 15716636
TI  - Characterization of a new rat model of penetrating ballistic brain injury.
AB  - Penetrating brain injury (PBI) is a leading cause of mortality and morbidity in
      modern warfare and accounts for a significant number of traumatic brain injuries
      worldwide. Here we characterize the pathophysiology of a new rat model of PBI
      that simulates the large temporary cavity caused by energy dissipation from a
      penetrating bullet round. Male Sprague-Dawley rats (250-300 g) were subjected to
      a simulated ballistic wound to the right frontal hemisphere implemented by an
      inflatable penetrating probe. Three levels of injury severity were compared to
      control animals. Neurological and physiological outcome was assessed over a 3-day
      recovery period and brain tissue collected at 72 h for histopathological
      evaluation. Brain-injured regions included the ipsilateral frontal cortex and
      striatum with volumetric increases in intracranial hemorrhage (5-18 mm3) and
      lesion size (9-86 mm3) related to severity. Similarly, hemispheric swelling
      increased (3-14%) following PBI, associated with a significant rise in
      intracranial pressure. Astrogliosis was present in regions adjacent to the core
      injury along with microglial and leukocyte infiltration. Injury remote to the
      lesion was observed in the cerebral peduncle that may have accounted, in part,
      for observed neurological deficits. Neurological and balance beam testing
      revealed sensorimotor deficits that persisted through 72 h. Severe
      electroencephalographic disturbances included the occurrence of cortical
      spreading depression, slow-waves, and brain seizure activity. In conclusion, this
      rat PBI model replicates diverse, salient features of clinical PBI pathology,
      generates reproducible and quantifiable measures of outcome, and is scalable by
      injury severity, rendering it an attractive vehicle for experimental brain trauma
      research.

PMID- 15716637
TI  - Estimated extent of cross-resistance to ritonavir-boosted protease inhibitors
      among protease inhibitors-experienced patients: implications for tipranavir use.

PMID- 15716638
TI  - Oral candidosis as a clinical marker of immune failure in patients with HIV/AIDS
      on HAART.
AB  - Oral candidosis (OC) has been proposed as a clinical marker of highly active
      antiretroviral therapy (HAART) success or failure. The principal objective of
      this work was to assess whether the presence OC is associated with immunologic or
      virologic failure in patients with HIV/AIDS undergoing HAART. One hundred fifty
      one patients with HIV/AIDS from Regional Hospital "Carlos Haya," Malaga, Spain,
      were examined orally. All patients had been undergoing HAART for a minimum of 6
      months prior to oral examination. OC diagnosis was in accordance with World
      Health Organization-Centers for Disease Control (WHO-CDC) criteria. Age, gender,
      route of HIV infection, CD4 lymphocyte counts, and viral load were taken from the
      medical records. In regard to HAART response the patients were classified as:
      virologic- responders (viral load < 50 copies per milliliter), virologic
      nonresponders (viral load >50 copies per milliliter); immunologic responders (CD4
      cells counts > 500 per milliliter), and immunologic nonresponders (CD4 cells
      counts < 500 per milliliter). Prevalence of OC was determined for each group. The
      presence of OC was closely related to immune failure (p 0.006; odds ratio [OR]
      3.38 95% confidence interval [CI] 1.262-12.046) in patients with HIV/AIDS
      undergoing HAART. The probability of immune failure in the presence of OC was 91%
      for men who have sex with men, 95.5% for heterosexuals, and 96% for intravenous
      drug users. In conclusion, OC should be considered a clinical marker of immune
      failure in patients with HIV/AIDS undergoing HAART.

PMID- 15716639
TI  - Integrating hepatitis C services into existing HIV services: the experiences of a
      sample of U.S. drug treatment units.
AB  - Hepatitis C virus (HCV) is the most prevalent blood-borne infectious disease in
      the United States, especially among drug users, and coinfection with HIV is
      common. Because drug users are often medically underserved, drug treatment units
      are important sites of opportunity for providing services for these infectious
      diseases. Given the commonalities in the routes of transmission of HIV and HCV,
      and the fact that many drug treatment units have established an infrastructure to
      provide HIV services, some have suggested integrating HCV services into those
      already established for HIV. Using data collected in a telephone survey with 89
      drug treatment units throughout the United States, this paper examines the extent
      to which drug treatment units have expanded their HIV services to include those
      for HCV, and the extent to which this expansion was facilitated by having HIV
      services in place. Overall, a greater proportion of methadone maintenance than
      drug-free treatment units provided services for HIV and HCV. The majority of
      units in both modalities that provided HIV- and HCV-related services expanded
      their HIV service delivery to include similar HCV services, and one third
      expanded all of their HIV services. A large number of these units, however,
      indicated that having an HIV service infrastructure did not facilitate this
      expansion, often because the units wanted to emphasize differences in the two
      viral infections. Policy makers and individual treatment units need to develop
      strategies that capitalize on existing infrastructures while maintaining the
      distinction between HIV and HCV primary and secondary prevention efforts.

PMID- 15716640
TI  - A brief mental health and substance abuse screener for persons with HIV.
AB  - Mental illness and substance abuse are common among HIV-infected individuals and
      are associated with negative outcomes, including poor medication adherence.
      Therefore, quick and effective methods for detecting these co-occurring disorders
      are necessary for health care practitioners. This article reports on the creation
      and preliminary testing of a brief screening tool, the Substance Abuse and Mental
      Illness Symptoms Screener (SAMISS). The 13-item screener was developed primarily
      from existing scales and administered to HIV-infected individuals receiving care
      at infectious diseases clinics in the Southeast. To assess the validity of the
      SAMISS, a subset of those who screened positive for both mental illness symptoms
      and substance use problems (n = 207) were administered the Structured Clinical
      Interview for DSMIV Disorders (SCID). The positive predictive value of the
      screener in comparison to the SCID was 98.6% for mental disorders and 98.6% for
      substance use disorders. The agreement between specific screener symptoms and
      their corresponding SCID diagnoses was relatively high for alcohol dependence
      (kappa = 0.50, p < 0.001), drug dependence (kappa = 0.30, p < 0.001), and drug
      abuse (kappa = 0.42, p <0.001). The finding that the screener is highly
      predictive of having a general mental disorder and substance use disorder among
      those screening positive for mental illness symptoms and substance use problems,
      as well as its brevity and ease of administration, make it a useful tool to
      detect symptoms of co-occurring disorders so that patients can be referred to
      mental health and substance abuse specialists. The screener is not a diagnostic
      instrument and has limited value in predicting specific psychiatric diagnoses.

PMID- 15716641
TI  - The process of disclosing HIV serostatus between HIV-positive mothers and their
      HIV-negative children.
AB  - The current study explores the impact of HIV disease on mothers as they face the
      task of balancing their own physical and psychological needs with the needs of
      their families as well as the additional burden of deciding whether to disclose
      their HIV status to their children. Qualitative interviews were conducted with 35
      women and 19 children 10-18 years of age. Mothers were interviewed about the
      experience of being an HIV-positive mother and issues regarding disclosure.
      Children were also interviewed about the experience of having a mother who is HIV
      positive and issues regarding disclosure. The decision to disclose was dependent
      on the child's developmental level, the degree of the mother's illness, and in
      some cases this decision was taken from mothers when someone else disclosed their
      HIV status to their children. Positive aspects of disclosure from the mother
      child dyads included open, honest communication, and closer relationships between
      mothers and their children. Common negative themes emanating from the data
      included fear, uncertainty, forced secrecy for fear of being ostracized based on
      the stigma associated with the disease, behavioral changes in the children, and
      shifting responsibilities between the mother and the child. Findings of the study
      suggest that disclosure, and all it entails, remains a vital issue for mothers
      who are HIV-positive. In addition, the findings reflected that children and their
      mothers have very different perspectives regarding the process and the effects of
      disclosure of the mother's HIV status. Clinical implications and recommendations
      for further research are discussed.

PMID- 15716642
TI  - Risk factors associated with posttraumatic stress disorder symptomatology in HIV
      infected women.
AB  - This study examined risk factors for posttraumatic stress disorder (PTSD)
      symptomatology in a sample of 102 HIV-positive women. The magnitude of HIV
      related PTSD symptoms was associated with a greater number of HIV-related
      physical symptoms, more extensive history of pre-HIV trauma, less perceived
      availability of social support, greater degree of perceived stigma, and greater
      degree of negative life events. Hierarchical multiple regression analysis
      revealed three individual predictors of PTSD symptomatology: total impact of
      negative life events, total stigma score, and total number of present symptoms.
      Stigma emerged as the strongest individual predictor. Social support failed to
      moderate relationships between PTSD symptomatology and HIV-related physical
      symptoms and negative life events. These findings may inform helping
      professionals about risk factors associated with PTSD symptomatology in HIV
      positive women.

PMID- 15716644
TI  - Combination pill approved in Europe.

PMID- 15716643
TI  - STD/AIDS knowledge, attitude, practice, and characteristics of market vendors in
      Hefei, China.
AB  - Little is known about the information on sexually transmitted disease (STD)/AIDS
      in the population working in congregating trading markets in China. A cross
      sectional study was conducted among three big congregating trading markets in
      Hefei City. Seven hundred fifty-two market vendors completed a questionnaire, 333
      of two markets provided specimen for STD/HIV testing. The majority of market
      vendors in China are sexually active youths and adults, and have little
      education. The market vendors had poor knowledge of STD/AIDS. The rates of
      correct answers to questions about STD/AIDS varied between 21.1%-81.9%. More than
      50% of the market vendors had a negative attitude toward HIV-infected
      individuals. Among the subjects, 27.6% had had premarital or extramarital sex;
      15.9% reported using condoms in the past 12 months. Among those who provided
      specimens, 3.9% were identified with STD, approximately 9 times higher than that
      in the general population of Hefei (0.4%). Our study suggests China should
      implement STD/HIV prevention interventions for market vendors to prevent STD/HIV
      infection.

PMID- 15716645
TI  - More use of female condom recommended.

PMID- 15716646
TI  - Guidelines for managing pressure ulcers with negative pressure wound therapy.
AB  - Pressure ulcers are a serious health issue, leading to clinical, financial, and
      emotional challenges. Numerous treatment modalities are available to promote
      wound healing, yet clinicians may be unsure how to incorporate these treatment
      options into an overall plan of care for the patient with a pressure ulcer. A
      consensus panel of experienced wound care clinicians convened in July 2004 to
      review the mechanisms of action and research basis for one such treatment
      modality: negative pressure wound therapy. After answering key questions about
      this modality, they developed an algorithm to assist the clinician in making
      decisions about using negative pressure wound therapy appropriately in patients
      with Stage III and Stage IV pressure ulcers.

PMID- 15716647
TI  - Ultrasound of the digestive tract in the 21st century.

PMID- 15716648
TI  - Anatomy of the GI tract in US: an historical perspective.
AB  - It is a basic interest of Man to look inside and understand the human body. This
      interest dates back to prehistoric times and is nowadays of diagnostic relevance
      in sick patients. It has led to the development of a variety of imaging methods
      for medical purposes within the 20th century. Among these, ultrasound is
      exceptionally appealing to both doctors and patients because of the wide variety
      of organs that can be investigated and because of its safety. The user, at any
      level, needs both theoretical knowledge and technical skills in its use. Various
      sites from the upper gastrointestinal tract to the anus are nowadays accessible
      by ultrasound. This review discusses the instruments for the sonographic
      evaluation of the gastrointestinal tract and gives an overview of their current
      applications.

PMID- 15716649
TI  - Doppler ultrasound and intravenous contrast agents in gastrointestinal tract
      disorders: current role and future implications.
AB  - Doppler sonography is part of the entire sonographic evaluation of intestinal
      diseases. It can help in estimating disease activity, although as the sole method
      to assess the patients situation it is not acceptable. New methods to quantify
      disease activity, such as contrast enhanced sonography, are at an experimental
      level and have to be evaluated in more detail.

PMID- 15716650
TI  - Ultrasonography and three-dimensional methods of the upper gastrointestinal
      tract.
AB  - Improved technology and new clinical methods have expanded the possibilities of
      using ultrasound in the daily routine of gastroenterology. Gastrointestinal
      ultrasonography can, in principle, be applied in two different ways in patient
      management. It can be used as one imaging modality among others, for which the
      clinicians refer the patient to a radiologist, but it can also be used as a
      clinical tool, similar to the stethoscope, expanding on the clinical findings and
      paving the way for efficient work-up of patients. Furthermore, ultrasonography
      has scientific applications; for example, strain rate imaging and three
      dimensional ultrasound are advanced methods that allow highly specified and
      detailed examination of the tissue or organ of interest.

PMID- 15716651
TI  - Imaging inflammatory bowel disease using bowel ultrasound.
AB  - During the last two decades the general availability of high resolution
      ultrasound has greatly improved the diagnostic potential of ultrasound in the
      assessment of inflammatory bowel disease (IBD). This technique has proved to be
      useful as a screening imaging modality in patients with symptoms or clinical
      signs that strongly indicate an inflammatory bowel disorder as well as for
      assessing the anatomical extension of Crohn's disease (CD) lesions at primary
      diagnosis. Another important indication is the follow-up of patients who are
      already known to have CD. Here, the technique may play a key role in the
      detection of luminal and mesentery complications or for the evaluation of disease
      extension during a clinical flare-up of both CD and ulcerative colitis. By
      contrast, the role of bowel ultrasound in the assessment of disease activity is
      limited so far, even though colour Doppler flow imaging may, perhaps, help to
      differentiate inflammatory from fibrotic intestinal strictures. New ultrasound
      technologies, such as those using oral and intravenous contrast agents, will
      probably further increase the diagnostic capability of ultrasound in this
      context, thus radically changing the diagnostic approach to IBD in the near
      future.

PMID- 15716652
TI  - Endoscopic ultrasonography: current clinical role.
AB  - Endoscopic ultrasonography appeared in the clinical arena almost 20 years ago and
      it has now become a well integrated technique in everyday hospital practice. More
      than 2000 scientific papers published in the literature have demonstrated its
      high accuracy for the diagnosis and staging of a variety of benign and malignant
      conditions. The instrumentation consists of a special endoscope, modified by a
      high-frequency ultrasound transducer placed on its tip, and an ultrasound driving
      unit. The main indications to endoscopic ultrasonography can be explained by its
      ability to visualize the gut wall as a multi-layer structure corresponding to
      histological layers. Other important indications derive from its capability of
      displaying, very closely, the structures and lesions surrounding the gut wall,
      such as the pancreato-biliary area, masses and lymph nodes. Fine-needle
      aspiration has become an indispensable adjunct to the technique since 1993, when
      it was shown to be feasible and safe to obtain tissue diagnosis in the majority
      of the lesions under the reach of endoscopic ultrasonography. In recent years,
      some authors have dealt with the practical clinical applications of endoscopic
      ultrasonography, validating its use in many diagnostic and staging algorithms and
      showing that it is cost-effective and significantly affects patient outcome.

PMID- 15716653
TI  - Oesophageal intraluminal impedance can identify subtle bolus transit
      abnormalities in patients with mild oesophagitis.
AB  - In a subgroup of patients with non-erosive gastroesophageal reflux disease (GORD)
      or mild oesophagitis, acid clearance is prolonged in spite of favourable gravity
      and normal or minimally impaired oesophageal peristalsis. Dysphagia is rare in
      this group but might also be present or develop after anti-reflux surgery. The
      causal relationship between prolonged clearance or dysphagia and oesophageal body
      dysmotility in these patients is not completely clear. New techniques are now
      available to assess oesophageal motility and transit and might help to detect
      more subtle defects underlying functional impairment in patients with GORD.
      Combined video-fluoroscopy and intraluminal impedance indicate an excellent
      correlation between both methods in detecting oesophageal bolus transit. Combined
      intraluminal impedance and manometry has the capability to evaluate oesophageal
      contractions and bolus transit without the use of radiation. Subtle bolus transit
      abnormalities were identified in a small proportion of patients with mild
      oesophagits and normal oesophageal peristalsis. Outcome data are needed to
      evaluate the prognostic value of combined manometry-impedance in patients with
      GORD undergoing anti-reflux surgery.

PMID- 15716654
TI  - Diagnostic model of esophageal varices in alcoholic liver disease.
AB  - Esophageal varices may cause life-threatening bleeding with attendant high
      hospital cost. Since effective preventive modalities for variceal hemorrhage have
      been established, early detection of esophageal varices is critical for
      prevention of bleeding. Currently, endoscopic screening is widely recommended to
      patients who have the diagnosis of cirrhosis. However, the diagnosis of cirrhosis
      relies on histological evaluations, which is costly and invasive, and endoscopic
      screening also burdens medical resources. Recent cost-effectiveness studies
      suggested that empiric prophylaxis with beta-blockers may be viable in comparison
      with endoscopic screening in patients with cirrhosis. However, this issue need to
      be also evaluated taking account of societal and patient perspectives and is not
      yet decided. An accurate non-invasive diagnostic model to predict the presence of
      esophageal varices may reduce unnecessary endoscopic procedures and prophylactic
      medication and improve cost-benefit of these approaches. Use of an accurate serum
      marker for severe hepatic fibrosis may also improve accuracy of non-invasive
      diagnostic models. Hyaluronic acid, a serum marker for severe hepatic fibrosis,
      has been reported to have a high diagnostic performance in assessing the severity
      of hepatic fibrosis in patients with alcoholic liver disease. In this issue, a
      non-invasive diagnostic model including hyaluronic acid was shown to have
      excellent performance in excluding the presence of medium to large esophageal
      varices in severe alcohol abusers. Based on current evidence, the strategy of
      using a non-invasive diagnostic model together with a serum marker for severe
      hepatic fibrosis may improve cost-benefit in the prevention of variceal
      hemorrhage among patients with alcoholic liver disease. The independent
      verification of such diagnostic models is needed.

PMID- 15716655
TI  - Gene polymorphisms as predictors of decreased bone mineral density and
      osteoporosis in primary biliary cirrhosis.
AB  - Osteoporosis is a common complication observed in patients with primary biliary
      cirrhosis (PBC), with a prevalence of around 25%. The pathogenesis of bone loss
      in PBC is not well understood, since low bone formation and high resorption have
      been described. Bone disease is influenced by the duration and severity of the
      disease and oestrogen deficiency secondary to menopause. Genetic susceptibility
      has also been considered for osteoporosis in PBC, including vitamin D receptor
      genotypes, the gene encoding collagen type I alpha1 and insulin growth factor 1
      gene microsatellite repeat polymorphism. Based on current evidence, the proposed
      genotypes either do not influence the development of osteoporosis in PBC or play
      only a minor role in it. The duration as well the severity of cholestasis are the
      main factors for such a disturbance since they are associated with the degree of
      bone loss. These features may exceed the potential effect of gene polymorphisms
      on osteoporosis in PBC.

PMID- 15716656
TI  - Critical issues in the identification and management of patients with hereditary
      non-polyposis colorectal cancer.
AB  - Inherited defects of the DNA mismatch repair system are the underlying cause of
      the hereditary non-polyposis colorectal cancer (HNPCC) syndrome and are
      responsible for 3-4% of all cases of colorectal cancer. The HNPCC syndrome also
      carries the risk of development of additional malignancies such as endometrial,
      stomach, small bowel, ovarian, pancreas, ureter, renal pelvis, biliary tract and
      brain tumours. Amsterdam I and II criteria have been developed to clinically
      identify affected families. The revised Bethesda criteria function to select
      patients whose tumours should be investigated for microsatellite instability, the
      molecular hallmark of defects of the DNA mismatch repair proteins such as hMLH1
      and hMSH2. Microsatellite instability-positive cases should be investigated for
      germline defects in the respective genes. This facilitates identification of
      affected family members that have to be included in special surveillance
      programmes, while unaffected family members are spared the physical discomfort
      and psychological burden of cancer surveillance. In this article, strategies for
      effective clinical as well as genetic detection of affected individuals,
      surveillance and appropriate preventive measures are discussed. Open questions
      include the role of chemoprevention, preventive surgical procedures, new
      endoscopic procedures as well as non-invasive 'virtual colonoscopy' and the exact
      implications of some mutations of the DNA mismatch repair genes. Perhaps most
      importantly, efforts should be made to more efficiently transfer information
      about the HNPCC syndrome and the cancer risk associated with it from the
      specialists to primary health care providers and the general public.

PMID- 15716657
TI  - Characteristics of oesophageal bolus transport in patients with mild
      oesophagitis.
AB  - OBJECTIVE: Patients with gastroesophageal reflux disease (GORD) frequently have
      oesophageal motility disturbance. However, detailed data about bolus transport
      characteristics in these patients are still lacking. In the present study the new
      technology of concurrent impedance manometry was applied for characterization of
      oesophageal motor function in patients with mild GORD. METHODS: Oesophageal
      motility testing was performed in 25 patients with mild GORD (group 1) as
      compared to 25 healthy subjects (group 2) employing the technique of concurrent
      impedancometry and manometry. Oesophageal motility as well as patterns and
      parameters of bolus transport after the swallowing of saline or yogurt were
      analysed. RESULTS: According to manometry the velocity of the contraction wave
      was similar in both groups. Mid-distal contraction amplitude in group 1 was still
      in the normal range but significantly lower than in group 2 (57.4+/-4.5 mmHg vs
      91.4+/-7.5 mmHg for saline, and 47+/-4.1 vs 80.7+/-9.4 mmHg for yogurt).
      According to impedance measurements, bolus transport was significantly slower
      (3.6+/-0.1 vs 4.0+/-0.1 cm/s for saline and 3.0+/-0.1 vs 3.2+/-0.1 cm/s for
      yogurt), and post-deglutitive impedance was significantly lower in group 1: 2110
      omega+/-116 omega versus 2542 omega+/-152 omega (P<0.01) with saline and 1862
      omega+/-108 omega versus 2348 omega+/-148 omega with yogurt (P<0.01). GORD
      patients showed several pathological bolus transport patterns, which were not
      observed in healthy subjects. Gastroesophageal liquid reflux was observed between
      the swallows. CONCLUSIONS: In patients with mild GORD concurrent impedancometry
      and manometry is sufficiently sensitive for the detection of minor oesophageal
      dysmotility. Several pathological features have been characterized including
      delayed bolus transport, impaired propulsive volume clearance, pathological
      transport patterns and pathological reflux patterns.

PMID- 15716658
TI  - Serum fibrosis markers can detect large oesophageal varices with a high accuracy.
AB  - OBJECTIVES: The aim of this study was to determine the value of serum fibrosis
      markers for the diagnosis of oesophageal varices in alcoholic patients. METHODS:
      Fifty-four sets of clinical and biochemical data, including serum markers of
      fibrosis, obtained from 146 heavy alcohol drinkers (106 men, 40 women; mean age
      49.2+/-9.0 years) without any history of variceal bleeding were analysed.
      Gastroscopy and liver biopsy were performed in all patients. Multivariate
      analysis was performed to identify the markers best correlated with oesophageal
      varices. RESULTS: Fifty-nine patients (40.4%) had severe fibrosis (3+) and 48
      (32.9%) had oesophageal varices (all grades considered together). In multivariate
      analysis, a prothrombin index below 60%, alkaline phosphatase activity over 110
      IU/l, and hyaluronate over 100 g/l were the best markers for the prediction of
      oesophageal varices. The diagnostic accuracy for medium to large oesophageal
      varices using these three factors was 86%. Eight patients (16.7%) with
      oesophageal varices presented no or moderate fibrosis (F<3): one patient (12.5%)
      had an alkaline phosphatase level >110 IU/l. However, all eight of these patients
      had small oesophageal varices. CONCLUSIONS: These three non-invasive markers
      correctly predict the presence or absence of medium to large oesophageal varices
      in 86% of alcoholic patients.

PMID- 15716659
TI  - Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis.
AB  - OBJECTIVE: Thrombophilic gene mutations have been reported to be associated with
      the formation of portal vein thrombosis (PVT). This study aimed to investigate
      the role of thrombophilic gene mutations in cirrhotic patients with PVT. PATIENTS
      AND METHODS: A total of 74 cirrhotic patients (17 with PVT, 57 without PVT), and
      19 non-cirrhotic patients with PVT and 80 healthy controls were included. Factor
      V Leiden G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase
      C677T mutations were analysed by restriction fragment length polymorphism.
      RESULTS: Aetiologies and Child-Pugh distribution of cirrhotic patients with and
      without PVT were similar. Five of 17 (29%) of cirrhotic patients with PVT but
      only two of 57 (3.5%) of cirrhotics without PVT, five of 80 (6%) of controls and
      none of the 19 non-cirrhotic patients with PVT had factor V Leiden G1691A
      mutation (P<0.05). Prothrombin G20210A mutation was found in five (29%) cirrhotic
      patients with PVT while only two (3.5%) cirrhotic patients without PVT, one (5%)
      non-cirrhotic patient with PVT and two (2.5%) controls had this mutation
      (P<0.05). The frequency of the homozygote methylenetetrahydrofolate reductase
      677C-T mutation was similar in all four groups. CONCLUSIONS: Inherited
      thrombophilic gene mutations appear to increase the risk of PVT formation in
      cirrhotic patients but not in patients without liver disease in a cohort of
      Turkish patients.

PMID- 15716660
TI  - Serum lipid profile and hepatic steatosis of adult beta-thalassaemia patients
      with chronic HCV infection.
AB  - OBJECTIVES: The aim of this study was to evaluate the serum lipid profile and to
      assess the prevalence of hepatic steatosis in adult beta-thalassaemic patients
      with chronic hepatitis C virus (HCV) infection. METHODS: Thirty-five adult HCV
      infected, multi-transfused, beta-thalassaemia patients (beta-HCV patients), 63
      otherwise normal patients with chronic HCV infection (HCV patients) and 54 beta
      thalassaemia patients without chronic viral hepatitis (beta patients) were
      studied. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol (LDL-C), triglycerides, viral markers and liver
      histology were evaluated. RESULTS: Serum total cholesterol, HDL-C and LDL-C were
      found at significantly lower levels in beta-HCV and beta patients than in HCV
      patients. Triglyceride levels were significantly lower in the HCV group compared
      with the beta group. Nine (25.7%) of the 35 beta-HCV patients had mild hepatic
      steatosis. Thirteen (23.6%) of 55 HCV patients presented mild and 4/55 (7.3%)
      moderate hepatic steatosis. None of the beta group presented steatosis. When we
      compared beta-HCV and HCV patients with steatosis, we found that beta-HCV
      patients had a lower degree of steatosis (11.1+/-7% vs 22.9+/-17.2%, P=0.021).
      Multivariate logistic regression analysis showed that the only independent
      predictor associated with hepatic steatosis in beta-HCV and HCV patients was
      genotype 3a (OR, 3.61; 95% CI, 1.22-10.71, P=0.021). CONCLUSIONS: Adult beta
      thalassaemia patients, compared to other patients with chronic HCV infection,
      present lower cholesterol levels (total cholesterol, HDL, LDL) and similar
      frequency but a lower degree of hepatic steatosis. This difference in the degree
      of steatosis is most likely due to the higher prevalence of genotype 3a in the
      non-beta-thalassaemia group.

PMID- 15716661
TI  - Fatigue is not a specific symptom in patients with primary biliary cirrhosis.
AB  - BACKGROUND: Fatigue has been reported to be common in patients with primary
      biliary cirrhosis (PBC). Limited data exist on comparison with fatigue in the
      general population and comparison with patients with other chronic
      gastrointestinal disorders are lacking. METHOD: We enrolled 96 patients with PBC
      (87 females); mean age 63 (range 34-65) who completed the Fatigue Impact Scale
      (FIS). In comparison we included matched controls from the general population,
      patients with organic (OGD) and functional GI disorders (FGD). Liver function
      test and the latest liver biopsy were analysed and correlated with fatigue
      scores. RESULTS: The mean duration of PBC was 7.4 years, the mean bilirubin 13
      micromol/l. Twelve per cent of patients had cirrhosis, 29% were in stage I on
      Ludwig's histology score and 30% and 29% were in stages II and III, respectively.
      The PBC patients had a median FIS total score of 29 in comparison with 38 in GP
      controls (P<0.05). Patients with OGD and FGD had more severe fatigue (FIS total
      score 67 and 59 (P<0.01 compared with PBC)). Fatigue in the PBC patients did not
      correlate with liver tests and histology stage. CONCLUSION: PBC patients had less
      severe fatigue measured with the FIS than controls from the GP and patients with
      OGD and FGD. This study also confirms results of other studies showing no
      correlation with fatigue in PBC and liver disease parameters. These results
      argues strongly against fatigue as a specific symptom in PBC.

PMID- 15716662
TI  - Hereditary vacuolar internal anal sphincter myopathy causing proctalgia fugax and
      constipation: a new case contribution.
AB  - Hereditary anal sphincter myopathy is rare. We present a family with one affected
      member with proctalgia fugax, constipation and internal anal sphincter
      hypertrophy. Ultrastructural findings show vacuolization of smooth muscle cells
      without the characteristic polyglucosan inclusion. Further relief of symptoms was
      obtained using an oral calcium antagonist. Based on clinical presentation,
      endosonography and morphological findings, we consider our case is a histological
      variant of the vacuolar myopathy originally described.

PMID- 15716663
TI  - Continuous cytokine exposure of colonic epithelial cells induces DNA damage.
AB  - OBJECTIVE: Chronic inflammatory diseases of the intestinal tract are associated
      with an increased risk of colorectal cancer. As an example ulcerative colitis
      (UC) is associated with a production of reactive oxygen species (ROS), including
      nitrogen monoxide (NO), which is produced in high amounts by inducible nitrogen
      oxide synthase (iNOS). NO as well as other ROS are potential DNA damaging agents.
      The aim was to determine the effect of long-term cytokine exposure on NO
      formation and DNA damage in epithelial cells. METHODS: A colonic cell line (HT29)
      was stimulated for 1-10 weeks with interferon-gamma (IFN-gamma) or tumour
      necrosis factor-alpha (TNF-alpha) or both and compared with unstimulated cells or
      cells stimulated for 48 h. Cells were co-incubated with a selective iNOS
      inhibitor (N-monomethyl-L-arginine (L-NMMA)) in some experiments. Viability was
      assessed by the dimethylthiazol diphenyl tetrazolium bromide (MTT) test.
      Production of ROS was determined by the oxidation of 2',7'
      dichlorodihydrofluorescein to a fluorescent 2',7'-dichlorofluorescein and
      measured by fluorescence reading and visualized by fluorescence microscopy. DNA
      stability was determined by single cell gel electrophoresis. RESULTS:
      Continuously stimulated colonic cells had increased ROS production, especially
      those stimulated with TNF-alpha or IFN-gamma/TNF-alpha (P<0.001). The ROS
      production could be inhibited by L-NMMA co-incubation, indicating that iNOS is
      responsible for the up-regulation (P<0.05). Continuously stimulated cells had
      increased DNA instability (P<0.002), whereas short-term stimulated cells did not.
      The DNA instability was inhibited by L-NMMA co-incubation (P<0.05). CONCLUSIONS:
      Continuous cytokine exposure induces an iNOS dependent up-regulation of ROS
      production and DNA instability. This mechanism could be involved in
      carcinogenesis in chronic inflammatory diseases of the intestinal tract.

PMID- 15716664
TI  - Evaluation of a new DNA test compared with the lactose hydrogen breath test for
      the diagnosis of lactase non-persistence.
AB  - BACKGROUND AND AIMS: Recent publications have found that the CC genotype of the
      DNA variant -13910 T/C upstream of the LCT gene is associated with lactase non
      persistence. We therefore compared the value of DNA testing for this variant (DNA
      test) with the lactose hydrogen breath test (H2 test), which is the clinical
      standard for the diagnosis of lactase non-persistence. PATIENTS AND METHODS: One
      hundred and twenty-three consecutive patients with suspected lactose
      malabsorption were tested for the presence of the -13910 T/C variant by
      polymerase chain reaction-restriction fragment length polymorphism analysis.
      These patients also underwent the H2 test after ingestion of 50 g lactose.
      RESULTS: Thirty-seven subjects had a CC genotype of the -13910 T>C polymorphism
      suggesting lactase non-persistence; 36 (97%) had also a positive H2 test. Eighty
      six subjects had either a TC or a TT genotype suggestive of lactase persistence.
      Seventy-four (86%) of these tested negative on the H2 test, while 12 patients had
      a positive H2 test. In eight of these 12 patients duodenal biopsies showed no
      evidence of small bowel disease. One patient carrying a CC genotype had a
      negative H2 test. In this patient the rise in serum glucose after oral lactose
      was normal, furthermore H2 non-excretion was also excluded. CONCLUSIONS: An
      excellent correlation is observed between a CC genotype and a positive H2 test,
      whereas the correlation between a TC or TT genotype and a negative H2 test result
      is less strong. Analysis of the -13910 T/C variant can be considered a good test
      for predicting the presence of lactase non-persistence in a patient population
      with suspected lactose malabsorption.

PMID- 15716665
TI  - Lack of efficacy of a reduced microparticle diet in a multi-centred trial of
      patients with active Crohn's disease.
AB  - BACKGROUND AND AIMS: Dietary microparticles, which are bacteria-sized and non
      biological, found in the modern Western diet, have been implicated in both the
      aetiology and pathogenesis of Crohn's disease. Following on from the findings of
      a previous pilot study, we aimed to confirm whether a reduction in the amount of
      dietary microparticles facilitates induction of remission in patients with active
      Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled
      trial. METHODS: Eighty-three patients with active Crohn's disease were randomly
      allocated in a 2 x 2 factorial design to a diet low or normal in microparticles
      and/or calcium for 16 weeks. All patients received a reducing dose of
      prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index,
      Van Hees index, quality of life and a series of objective measures of
      inflammation including erythrocyte sedimentation rate, C-reactive protein,
      intestinal permeability and faecal calprotectin. After 16 weeks patients returned
      to their normal diet and were followed up for a further 36 weeks. RESULTS:
      Dietary manipulation provided no added effect to corticosteroid treatment on any
      of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1
      year); e.g., for logistic regression of Crohn's disease activity index based
      rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low
      microparticle groups. CONCLUSIONS: Our adequately powered and carefully
      controlled dietary trial found no evidence that reducing microparticle intake
      aids remission in active Crohn's disease.

PMID- 15716683
TI  - Why blockade of the renin-angiotensin system reduces the incidence of new-onset
      diabetes.
AB  - Recent trials have suggested that inhibitors of the renin-angiotensin system
      (RAS), such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
      receptor blockers (ARBs), may reduce the incidence of new-onset diabetes in
      patients with or without hypertension and at high risk of developing diabetes. In
      this review, we critically evaluate the evidence from recent clinical trials for
      such a potential preventive effect of ACE inhibitors and ARBs, including a meta
      analysis of these recent trials. The reduced incidence of diabetes in patients at
      high risk of developing diabetes by ACE inhibitors or ARBs has been explained by
      haemodynamic effects, such as improved delivery of insulin and glucose to the
      peripheral skeletal muscle, and non-haemodynamic effects, including direct
      effects on glucose transport and insulin signalling pathways, all of which
      decrease insulin resistance. There is now evidence that the pancreas may contain
      an in situ active RAS, which appears to be upregulated in an animal model of type
      2 diabetes. Thus, ACE inhibitors and ARBs may act by attenuating the deleterious
      effect of angiotensin II on vasoconstriction, fibrosis, inflammation, apoptosis
      and beta-cell death in the pancreas, thereby protecting a critical beta-cell mass
      essential for insulin production. New evidence is presented that ACE inhibitors
      and ARBs may delay or prevent the development of insulin resistance and diabetes,
      for which novel mechanisms are suggested. The actions of agents that interrupt
      the RAS on insulin resistance, obesity and diabetes warrant further investigation
      in other animal models. Prospective clinical studies with the primary endpoint of
      the prevention of diabetes are now indicated to (i) further explore whether the
      inhibitors of the RAS are superior compared to other antihypertensive agents such
      as calcium channel blockers (CCBs) and (ii) to evaluate the potential beneficial
      effects of combination antihypertensive regimens on the development of diabetes.

PMID- 15716685
TI  - Assessing the prognostic relevance of blood pressure variability: discrepant
      information from different indices.

PMID- 15716684
TI  - Effect of dietary fiber intake on blood pressure: a meta-analysis of randomized,
      controlled clinical trials.
AB  - OBJECTIVE: We conducted a meta-analysis of 25 randomized controlled trials
      published in English-language journals before February 2004, to assess the effect
      of dietary fiber intake on blood pressure (BP). DESIGN: Using a standardized
      protocol, information on study design, sample size, participant characteristics,
      duration of follow-up and change in mean BP, was abstracted. The data from each
      study were pooled using a random effects model to provide an overall estimate of
      dietary fiber intake on BP. INTERVENTION: Dietary fiber intake was the only
      significant intervention difference between the active and control groups.
      RESULTS: Overall, dietary fiber intake was associated with a significant -1.65
      mmHg [95% confidence interval (CI), -2.70 to -0.61] reduction in diastolic BP
      (DBP) and a non-significant -1.15 mmHg (95% CI, -2.68 to 0.39) reduction in
      systolic BP (SBP). A significant reduction in both SBP and DBP was observed in
      trials conducted among patients with hypertension (SBP -5.95 mmHg, 95% CI, -9.50
      to -2.40; DBP -4.20 mmHg, 95% CI, -6.55 to -1.85) and in trials with a duration
      of intervention > or = 8 weeks (SBP -3.12 mmHg, 95% CI, -5.68 to -0.56; DBP -2.57
      mmHg, 95% CI, -4.01 to -1.14). CONCLUSIONS: Our results indicate that increased
      intake of dietary fiber may reduce BP in patients with hypertension and suggests
      a smaller, non-conclusive, reduction in normotensives. An intervention period of
      at least 8 weeks may be necessary to achieve the maximum reduction in BP. Our
      findings warrant conduct of additional clinical trials with a larger sample size
      and longer period of intervention to examine the effect of dietary fiber intake
      on BP.

PMID- 15716686
TI  - Blood pressure and outcomes in clinical trials.

PMID- 15716687
TI  - Benefits and safety of long-acting calcium antagonists in coronary artery
      disease: the Action Trial.

PMID- 15716688
TI  - Results of blood pressure screening in a population of school-aged children in
      the province of Milan: role of overweight.
AB  - OBJECTIVES: To study the prevalence of high blood pressure (BP) in an Italian
      paediatric population, and to verify whether in this population elevated BP
      values are associated with overweight (OW). STUDY DESIGN: Children (1206 males,
      1210 females) from the lower-grade public schools (ages 6-11 years) were studied.
      Body weight, height and BP were measured in each child. Elevated BP was defined
      if resting systolic and/or diastolic BP values equalled or exceeded the 95th
      percentile according to gender, age and height, based on the US normative BP
      tables. Overweight children were identified using four different methods: (1) the
      classification based on the relative body weight; (2) the French references by
      Rolland-Cachera et al. (Am J Clin Nutr 1982; 36:178-184); (3) the International
      Obesity Task Force charts; and (4) the Italian charts defined by Cacciari et al.
      (Eur J Clin Nutr 2002; 56:171-180). RESULTS: The prevalence of high BP in our
      population was 4.2% and was significantly higher in females (65/1210 = 5.4%) than
      in males (37/1206 = 3.1%), P = 0.005. The different methods used to define OW
      provide different estimates of OW prevalence (from 17.0 to 38.6%). The percentage
      of high BP subjects was significantly higher in OW than in normal-weight children
      regardless of the method used for the definition of the weight class (P <
      0.0001), in both genders. In addition, for each age range, absolute systolic and
      diastolic BP values were higher in OW as compared to normal-weight children both
      in males and in females (P < 0.0001). CONCLUSIONS: Our study indicates the
      importance of performing BP screenings in the paediatric population, and to
      promote interventions that may reduce the prevalence of OW in children.

PMID- 15716689
TI  - Bell or diaphragm in the measurement of blood pressure?
AB  - BACKGROUND: International guidelines have given diverse recommendations as to
      which side of the stethoscope should be used in the measurement of blood
      pressure. OBJECTIVE: To determine if there is any difference between the bell and
      the diaphragm sides of the ordinary acoustic stethoscope in the measurement of
      blood pressure. DESIGN AND METHODS: We compared, in random order, the bell and
      the diaphragm side of the ordinary acoustic stethoscope and also the effect of
      low- and high-frequency amplification with an electronic stethoscope in the
      measurement of blood pressure, in 250 adults. SETTING: Department of Medicine,
      Turku University Central Hospital. RESULTS: No statistically significant
      difference was seen between the bell side and the diaphragm side of the acoustic
      stethoscope, either in systolic blood pressure (SBP; mean +/- SD 129.5 +/- 21.7
      and 129.4 +/- 20.8 mmHg, respectively) or diastolic blood pressure (DBP; 77.0 +/-
      12.0 and 77.1 +/- 12.0 mmHg, respectively). Both the low-frequency (130.7 +/-
      22.5 mmHg) and the high-frequency (131 +/- 22.2 mmHg) amplification of systolic
      Korotkoff sounds yielded significantly greater values of SBP than were measured
      either with the bell (P = 0.008 compared with low frequency, P = 0.0005 compared
      with high frequency) or the diaphragm (P = 0.004 compared with low frequency, P =
      0.0001 compared with high frequency). Low-frequency amplification of DBP (76.4 +/
      12.3 mmHg) yielded values significantly lower than those measured with the bell
      (P = 0.04) or the diaphragm (P = 0.01). Values from high-frequency amplification
      of DBP (77.2 +/- 12.3 mmHg) did not differ significantly from those measured with
      the acoustic stethoscope. CONCLUSIONS: Both sides of the acoustic stethoscope
      give similar results in the measurement of office blood pressure and either side
      can be used in the reliable measurement of blood pressure.

PMID- 15716690
TI  - A reliable index for the prognostic significance of blood pressure variability.
AB  - OBJECTIVES: This study presents a reliable index inspired by the total
      variability concept of real analysis in mathematics, called average real
      variability (ARV), for the prognostic significance of blood pressure variability
      (BPV) overcoming the pitfalls of the commonly used standard deviation (SD).
      BACKGROUND: Recent studies have suggested that an increase in BPV is associated
      with an increase in subsequent cardiovascular events/complications. However,
      there are other studies where the cited association was not found or was lost in
      the presence of other well-known risk factors. An explanation for these
      apparently contradictory results may be the selection of the variability index
      used (SD). METHODS: Ambulatory blood pressure monitoring in 312 subjects aged >
      or = 55 years. Logistic regression models and survival methods were used to
      establish the prognostic significance of awake systolic BPV: in particular, (i)
      the performance of ARV versus SD, and (ii) the value of BPV relative to other
      well-known risk factors. RESULTS: The analyses using the ARV index show a
      statistically significant relative risk equal to 4.548 (P = 0.006) for the group
      with high BPV with respect to the low BPV group (reference level); in contrast,
      the corresponding relative risk associated to the SD index was not statistically
      significant. Furthermore, ARV exhibited a similar predictive value to systolic
      blood pressure. CONCLUSIONS: The proposed ARV index is a more reliable
      representation of time series variability than SD and may be less sensitive to
      the relative low sampling frequency of the ambulatory blood pressure monitoring
      devices. The results suggest that ARV adds prognostic value to the ABPM and could
      prompt the use of therapeutic measures to control BPV.

PMID- 15716691
TI  - Prevalence and clinical significance of a greater ambulatory versus office blood
      pressure ('reversed white coat' condition) in a general population.
AB  - BACKGROUND: Attention has recently been directed to a condition termed 'reversed
      white coat' because of an average 24 h ambulatory blood pressure (BP)
      uncharacteristically greater than office BP. No data are available, however, on
      the prevalence of this condition in the general population, as well as on its
      relationship to BP, age, gender, antihypertensive treatment and cardiac organ
      damage. METHODS: In 3200 individuals (participation rate 64%), randomly selected
      to be representative of the residents of Monza (Milan, Italy) for sex and decades
      of age (25 to 74 years), we measured office BP (average of three measurements,
      sphygmomanometry), ambulatory BP (automatic readings every 20 min, Spacelabs
      90207) and left ventricular mass (echocardiography). RESULTS: A 'reversed white
      coat' condition (identified when 24-h average ambulatory systolic, diastolic or
      mean were higher than the corresponding office values) was seen in 15%
      (diastolic) to 26% (systolic) of the population as a whole. Prevalence was
      greater (34-40%) when the difference between office and daytime BP was considered
      but in both instances it remained less than the prevalence of the white-coat
      phenomenon. A reversed white-coat condition was similarly frequent in males and
      females and showed a steep reduction with age and increasing office BP values.
      Prevalence was greater in hypertensive subjects in whom treatment achieved BP
      control than in untreated or unsatisfactorily treated individuals. Within each
      quartile of 24-h or office BP, left ventricular mass index adjusted for
      demographic and biochemical values was similar in reversed white coat versus the
      remaining subjects. The absence of any association with left ventricular
      hypertrophy scores against the clinical significance of this phenomenon.

PMID- 15716692
TI  - Night-time and diastolic hypertension are common and underestimated conditions in
      newly diagnosed apnoeic patients.
AB  - BACKGROUND: In newly diagnosed apnoeic patients without a history of
      hypertension, clinical hypertension is underdiagnosed in at least 40% of the
      cases. An increase in diastolic blood pressure is the most frequent pattern
      encountered. OBJECTIVE: To assess clinic and 24-h blood pressure, baroreflex
      sensitivity and left ventricular mass for identifying the prevalence, the type
      and the consequences of hypertension in newly diagnosed apnoeic patients.
      PATIENTS AND METHODS: Fifty-nine unselected patients (age = 48 +/- 12 years, body
      mass index = 28.1 +/- 4.5 kg/m2) referred to a university hospital sleep
      laboratory for symptoms suggesting obstructive sleep apnoea were included.
      Diagnosis of apnoea was accepted when respiratory disturbance index was > or =
      15/h of sleep. Blood pressure was considered as normal by their general
      practitioner and all of them were free of any medication for hypertension.
      Echocardiography, 24-hour ambulatory blood pressure monitoring and assessment of
      the baroreflex sensitivity were performed. RESULTS: Forty-two percent of the
      apnoeic patients demonstrated a clinical hypertension, 34 subjects (58%) had a
      daytime hypertension, and 45 patients (76%) had a night-time hypertension, using
      24-h monitoring. All the daytime hypertensives also had night-time hypertension.
      Forty-seven of the 59 patients (80%) were hypertensive either in the clinic or
      using 24-h recording. Diastolic and systolo-diastolic hypertension were the
      prominent types of hypertension observed both by clinic or ambulatory
      measurements. Respiratory disturbance index was significantly higher in apnoeic
      patients suffering isolated diastolic hypertension than in the normotensives
      (50.9 +/- 26.5/h versus 36.0 +/- 12.3/h, respectively; P = 0.02). The prevalence
      rate of left ventricular hypertrophy was high (between 15 and 20%) and occurred
      independently of associated hypertension. Baroreflex sensitivity was altered
      whatever the type of hypertension and decreased with the severity of obstructive
      sleep apnoea. CONCLUSION: Hypertension is hugely underdiagnosed in apnoeic
      patients unknown to be hypertensive. Use of 24-h blood pressure monitoring
      allowed the diagnosis of twice as much hypertension than did clinical
      measurement. Even at the beginning of their history of hypertension, apnoeic
      patients exhibited chronic adaptations of their cardiovascular system, as shown
      by early changes in baroreflex sensitivity and an increased prevalence of left
      ventricular hypertrophy.

PMID- 15716693
TI  - Impaired cardiovascular recovery following stress predicts 3-year increases in
      blood pressure.
AB  - OBJECTIVE: To assess whether variation in the rate of cardiovascular recovery
      following exposure to acute psychological stress predicts changes in blood
      pressure longitudinally, independently of blood pressure at baseline and other
      covariates. DESIGN: A 3-year longitudinal study. PARTICIPANTS: A total of 209 men
      and women aged 45-59 years at baseline, with no history of cardiovascular disease
      including hypertension. METHOD: Measurement of blood pressure, heart rate, heart
      rate variability, cardiac index and total peripheral resistance at rest, during
      two moderately stressful behavioural tasks and up to 45 min post-stress. Stress
      reactivity was defined as the difference in values between tasks and baseline,
      and post-stress recovery as the difference between recovery levels and baseline.
      OUTCOME MEASURES: Resting blood pressure measured at baseline and 3 years later.
      Seven individuals had been prescribed hypertensive medication on follow-up.
      RESULTS: Increases in systolic blood pressure (SBP) were predicted by impaired
      post-stress recovery of SBP (P < 0.001), diastolic blood pressure (DBP) (P <
      0.001) and total peripheral resistance (P = 0.003), independently of baseline
      blood pressure, age, gender, socio-economic status, hypertensive medication, body
      mass and smoking. The adjusted odds of an increase in SBP > or = 5 mmHg were 3.50
      [95% confidence interval (CI) 1.19 to 10.8] for individuals with poor compared
      with effective post-stress recovery of SBP. Three-year increases in diastolic
      pressure were predicted by impaired recovery of SBP (P < 0.001) and DBP (P =
      0.009) pressure and by heart rate variability during tasks (P = 0.002),
      independently of covariates. CONCLUSIONS: Impaired post-stress recovery and less
      consistently heightened acute stress reactivity may index disturbances in the
      regulation of cardiovascular stress responses that contribute to longitudinal
      changes in blood pressure in middle-aged men and women.

PMID- 15716694
TI  - Stromelysin-1 (MMP-3) gene 5A/6A promoter polymorphism is associated with blood
      pressure in a community population.
AB  - BACKGROUND AND OBJECTIVES: Arterial remodelling contributes to the development of
      hypertension. Stromelysin-1 (MMP-3), a member of the matrix metalloproteinase
      family may contribute to this process. Stromelysin-1 gene expression is partly
      regulated by a common polymorphism in the promoter region of either five or six
      consecutive adenosine bases (5A/6A). METHODS AND RESULTS: A cross-sectional study
      of 1111 randomly selected male and female community subjects (27-77 years), were
      assessed for conventional cardiovascular risk factors and stromelysin-1 5A-1171
      6A genotype. Multivariate analysis showed an independent association between the
      stromelysin-1 genotype and blood pressure that was recessive for the 5A/5A
      genotype. Subjects with the 5A/5A genotype had a higher mean systolic blood
      pressure (SBP) (+4.2 mmHg) and diastolic blood pressure (DBP) (+2.2 mmHg)
      compared to subjects with 5A/6A and 6A/6A genotypes. Subgroup analysis revealed
      an independent association of the 5A/5A genotype with SBP (+3.6 mmHg, P = 0.001)
      and DBP (+2.0 mmHg, P = 0.004) in subjects not on blood pressure medication.
      Whereas subjects with the 5A/5A genotype and taking medication had a higher mean
      SBP (+7.4 mmHg, P = 0.02) and DBP (+2.7 mmHg, P = 0.11). Multivariate analysis in
      the whole population showed there was no association between genotypes and mean
      intimal-medial wall thickness (IMT) (P = 0.87) or the likelihood of carotid
      plaque formation. CONCLUSIONS: The stromelysin-1 5A-1171-6A genotype is an
      important determinant of blood pressure in this general population sample.

PMID- 15716695
TI  - Role of the adducin family genes in human essential hypertension.
AB  - OBJECTIVE: In both humans and rats, polymorphisms of the alpha adducin (ADD1)
      gene are involved in renal sodium handling, essential hypertension and some of
      its organ complications. Adducin functions within cells as a heterodimer composed
      of various combinations of three subunits that are coded by three genes (ADD1, 2,
      3) each located on a different chromosome. DESIGN: These characteristics provide
      the biochemical basis for investigating epistatic interactions among these loci.
      METHODS: We examined the three adducin gene polymorphisms and their association
      with ambulatory blood pressure (ABPM) and with plasma levels of renin activity
      (PRA), endogenous ouabain (EO), in 512 newly discovered and never-treated
      hypertensive patients. RESULTS: Relative to carriers of the wild type (Gly/Gly)
      ADD1 gene, patients carrying the mutated Trp ADD1 allele had higher blood
      pressure (systolic blood pressure (SBP) 143.2 +/- 1.0 versus 140.6 +/- 0.6 mmHg P
      = 0.027 and diastolic blood pressure (DBP) 94.2 +/- 0.77 versus 92.3 +/- 0.5
      mmHg, P = 0.03), lower PRA and EO, consistent with the hypothesis of the renal
      sodium retaining effect of the Trp allele. Polymorphisms in the ADD2 and ADD3
      genes taken alone were not associated with these variables. However, the
      differences in SBP and DBP between the two ADD1 genotypes were greatest in
      carriers of the ADD3 G allele (around + 8 mmHg). The significance of the
      interaction between ADD1 and ADD3 ranged between P = 0.020 to P = 0.006 according
      to the genetic model applied. CONCLUSIONS: The interaction of ADD1 and ADD3 gene
      variants in humans is statistically associated with variation in blood pressure,
      suggesting the presence of epistatic effects among these loci.

PMID- 15716696
TI  - Benefits from angiotensin-converting enzyme inhibitor 'beyond blood pressure
      lowering': beyond blood pressure or beyond the brachial artery?
AB  - OBJECTIVE: The substantial benefits of ramipril over conventional therapy in high
      risk patients are not always associated with clinically significant differences
      in brachial arterial pressure, and largely remain unexplained. We undertook this
      acute study to establish the magnitude of and reason for different acute effects
      of ramipril and atenolol on arterial pressure. METHODS: We enrolled 30 patients,
      who took 10 mg ramipril, 100 mg atenolol, and placebo at intervals of > or = 7
      days, in a randomized, double-blind, placebo-controlled trial. After baseline,
      measurements were taken at 30-60 min intervals for 5 h, and comprised cuff
      brachial pressure, radial artery tonometry with generation of central aortic
      pressure, and pulse wave velocity for aorta, upper limb and lower limb arteries.
      RESULTS: Both ramipril and atenolol reduced arterial pressure, and the diastolic
      pressure fall was similar in the aorta and brachial artery, but the systolic
      pressure fall for ramipril was greater than for atenolol (by 5.2 mmHg, P <
      0.0001) in the aorta compared with the brachial artery. The aortic systolic
      pressure difference with ramipril in comparison with atenolol was accompanied by
      an absolute difference of 10.7% (P < 0.0001) in the augmentation index, denoting
      a reduction in peripheral wave reflection by ramipril. The aortic pulse wave
      velocity fell to a similar degree with ramipril in comparison with atenolol, but
      fell to a greater degree (1.35 and 0.44 m/s, respectively, P < 0.0001 for both)
      in muscular arteries of the lower and upper limbs. CONCLUSION: A greater
      (average, 5.2 mmHg) decrease in aortic systolic pressure caused by ramipril may
      explain the greater benefit of ramipril over atenolol. The difference is
      attributable to decreased stiffness of peripheral arteries and a reduction in
      wave reflection.

PMID- 15716697
TI  - Different relation between 24-h blood pressure and distensibility at different
      peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis
      (ELSA).
AB  - INTRODUCTION: The European Lacidipine Study on Atherosclerosis (ELSA) has been
      planned to investigate the effect of reduction in office and ambulatory blood
      pressure by lacidipine versus atenolol on carotid artery wall thickness in mild
      to moderate essential hypertensive patients with no metabolic abnormalities. One
      prespecified sub-study of ELSA focused on measurements of arterial distensibility
      in the carotid as well as in the radial artery to determine the relationship of
      functional arterial properties with office versus ambulatory blood pressure (BP)
      values as well as the correspondence between functional and structural arterial
      alterations. METHODS: The sub-study was conducted on 124 patients recruited in
      four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by
      a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid
      artery wall thickness was measured by certified sonographers as described in the
      main study. Common carotid and radial artery distensibility were obtained by
      echotracking techniques, which allowed to relate changes in arterial diameter
      with systo-diastolic BP changes. RESULTS: Carotid artery wall distensibility
      showed (1) a negative correlation with office and more so 24-h average systolic
      BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h
      diastolic BP) and (2) a negative correlation with the corresponding wall
      thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level
      distensibility and thickness showed no correlation with each other and with BP.
      Carotid (but not radial) artery distensibility also correlated with ambulatory
      systolic BP variability but the correlation was lost after adjustment for age and
      mean BP values. CONCLUSION: These data suggest that stiffening of large elastic
      artery is reflected more by ambulatory than office BP elevations, systolic BP
      being much more important than diastolic. Alterations of large elastic arteries
      function is related to structural wall changes. Functional and structural
      properties of middle-size muscle arteries are independent of BP.

PMID- 15716698
TI  - Reduction of peripheral flow reserve impairs endothelial function in conduit
      arteries of patients with essential hypertension.
AB  - BACKGROUND: A diminished flow reserve in resistance vessels is a hallmark of
      hypertensive microvascular disease. Hypertension is associated with structural
      alterations in the microcirculation and a reduced endothelium-dependent dilation
      in conduit arteries. Both have been demonstrated to predict future cardiovascular
      events. OBJECTIVE: We hypothesized that a reduced peripheral flow reserve impairs
      endothelial function in upstream conduit arteries in patients with arterial
      hypertension. DESIGN: In 43 hypertensive patients (HT) and 38 normotensive
      controls (NT) endothelial function of the brachial artery was assessed by
      measurement of flow-mediated dilatation (FMD), using high-resolution ultrasound.
      Peripheral flow reserve (FR) was determined via measurements of forearm blood
      flow at rest and during increments of reactive hyperaemia, using venous occlusion
      plethysmography. RESULTS: FMD was markedly impaired in HT (3.6 +/- 0.3%) as
      compared with NT (10.2 +/- 0.3%), whereas maximum brachial artery diameter
      following endothelium-independent dilatation was similar in both groups. In
      hypertensive patients FR was significantly reduced (HT, 3.2 versus NT, 6.0)
      during reactive hyperaemia after 5 min of ischaemia. FR was associated with FMD
      (r = 0.68, P < 0.01). Multiple stepwise regression analysis identified FR as a
      strong independent variable determining the extent of FMD (r2 = 0.46, P < 0.01).
      In HT the dose-response curve of FMD upon stepwise increases of FR was shifted
      significantly to the right. Normalization of FR improved FMD in HT by more than
      60%. CONCLUSIONS: In essential hypertension a reduced FR contributes to the
      endothelial dysfunction of upstream conduit arteries. These findings may have
      therapeutic and prognostic implications in patients with arterial hypertension.

PMID- 15716699
TI  - Hydrogen peroxide acts as both vasodilator and vasoconstrictor in the control of
      perfused mouse mesenteric resistance arteries.
AB  - BACKGROUND: Hydrogen peroxide (H2O2) plays a key role in the control of
      resistance artery (RA) tone and is hypothesized as an endothelial-derived
      hyperpolarizing factor. METHODS: In this study, we investigated the effects of
      the same concentration of exogenous H2O2 on mouse mesenteric RA tone induced by
      intraluminal pressure, G-protein coupled receptor activation and KCl. RAs were
      cannulated in an arteriograph in the absence or presence of vasoconstrictors.
      RESULTS: RA developed myogenic tone (MT) in response to stepwise pressure
      increases. Under phenylephrine, H2O2 induced a dose-dependent (1-50 micromol/l)
      vasodilation with maximum dilation at 50 micromol/l. H2O2 at 50 micromol/l
      induced a full dilation of RA under MT or contraction by phenylephrine that was
      independent of nitric oxide synthase, cyclooxygenase, endothelium and potassium
      channels iberiotoxin and apamin sensitive. The Ca2+ channel inhibitor,
      nimodipine, significantly blocked MT and also the contraction to phenylephrine
      and KCl. Under these conditions, H2O2 had no effect on RA diameter. Under KCl,
      the same concentration of H2O2 induced a potent vasoconstriction. This
      contraction involved p38 mitogen-activated protein-kinase activation but not
      ERK1/2. CONCLUSIONS: These findings provide the first evidence showing that the
      same and low concentrations of H2O2 can act as a relaxing factor but also as a
      vasoconstrictor under conditions in which hyperpolarization is compromised.

PMID- 15716700
TI  - Effects of glucose and insulin on the development of oxidative stress and
      hypertension in animal models of type 1 and type 2 diabetes.
AB  - OBJECTIVES: To investigate whether glucose or insulin is the cause of increases
      in oxidative stress and blood pressure in insulin-resistant animals, and to
      evaluate the effects of alpha-lipoic acid (LA) on the production of the
      superoxide anion (O2-) in the aorta and blood pressure elevations in various
      models of diabetes. METHODS: Two models of arterial hypertension combined with
      insulin resistance state and one model of insulin-dependent diabetes were studied
      in chronically glucose-fed rats (10% in drinking water), in animals chronically
      treated simultaneously with insulin (9 mU/kg per min with osmotic pumps) and
      glucose, and in rats initially treated with streptozotocin (50 mg/kg) and glucose
      during 4 weeks. These three groups of rats were treated either with a normal chow
      diet or with LA-supplemented diet. The oxidative stress was evaluated by the O2-
      production using the lucigenin-enhanced chemiluminescence method either in aortic
      or cultured smooth muscle cells from 12-week-old normotensive rats. Fasting blood
      glucose and insulin levels were measured after 4 weeks. RESULTS: At the end of
      the study, plasma levels of insulin and glucose as well as the insulin resistance
      index were found to be significantly higher in glucose-fed rats or in rats
      treated with insulin plus glucose compared with control rats (P < 0.01). Plasma
      glucose levels were elevated (P < 0.01) but plasma insulin levels were not
      modified in streptozotocin- and glucose-treated rats. Systolic blood pressure and
      aorta O2- production were found to be significantly higher in either glucose-fed
      rats (+20%) or in insulin plus glucose-treated rats (+24%) as compared with
      control rats (P < 0.01). Streptozotocin-induced diabetes with glucose treatment
      was not accompanied by increases in systolic blood pressure or in aortic O2-
      production. Rises in systolic blood pressure and in aortic O2- production were
      significantly attenuated either in glucose-fed (+10.3%) or in insulin plus
      glucose-fed (+8.7%) rats treated with LA. The simultaneous treatment with LA also
      attenuated the rise in insulin levels as well as in insulin resistance either in
      glucose-fed rats or in insulin plus glucose-treated rats. Moreover, LA was found
      to prevent the marked increases in O2- production in cultured smooth muscle cells
      chronically treated with high insulin combined or not with high glucose levels.
      CONCLUSIONS: These findings demonstrate that elevated plasma glucose levels alone
      do not induce vascular oxidative stress and hypertension unless it is combined
      with high level of insulin. The finding that the treatment with LA, a potent
      antioxidant, was efficacious in preventing oxidative stress and hypertension in
      diabetic models of insulin resistance suggests an important participation of
      oxidative stress in the development of hypertension in type 2 diabetes.

PMID- 15716701
TI  - Nebivolol decreases oxidative stress in essential hypertensive patients and
      increases nitric oxide by reducing its oxidative inactivation.
AB  - OBJECTIVE: To obtain further insight into the mechanism underlying the
      vasodilator effect of nebivolol. Since oxidative inactivation of nitric oxide
      (NO) is regarded as an important cause of its decreased biological activity, we
      studied (1) the effect of nebivolol on some oxidative parameters in essential
      hypertensive patients; (2) the effect of plasma of nebivolol-treated patients on
      reactive oxygen species production and NO availability in endothelial cells.
      METHODS: A total of 20 healthy subjects and 20 matched essential hypertensive
      patients treated with atenolol or nebivolol according to a double-blind,
      randomized design participated in the study. We measured low-density lipoprotein
      (LDL) and plasma hydroperoxides, 8-isoprostanes, oxidized LDL, susceptibility of
      LDL to oxidation (lag phase) and LDL vitamin E and the effect of plasma of
      nebivolol- and atenolol-treated patients on reactive oxygen species production
      and NO availability in endothelial cells exposed to oxidative stress. RESULTS: In
      hypertensive patients, nebivolol and atenolol significantly reduced blood
      pressure values after 4 weeks of treatment. Plasma and LDL hydroperoxides, plasma
      8-isoprostanes, plasma ox-LDL and LDL lag phase were significantly improved only
      in the patients receiving nebivolol compared with the atenolol group. Similarly
      there was a reduction of reactive oxygen species (ROS) and O2*- concentration in
      endothelial cells exposed to oxidative stress after incubation of the cells with
      plasma of the patients enrolled in the trial only in the patients receiving
      nebivolol compared to atenolol group. Furthermore, the reduction of basal and
      stimulated NO induced by oxidative stress in endothelial cells was significantly
      lower in the patients receiving nebivolol compared to atenolol group.
      CONCLUSIONS: The findings of the present study indicate that nebivolol, through
      its antioxidant properties, increases NO also by decreasing its oxidative
      inactivation.

PMID- 15716702
TI  - Sodium status and angiotensin-converting enzyme inhibition: effects on plasma
      angiotensin-(1-7) in healthy man.
AB  - OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors provide effective
      intervention for cardiovascular and renal disease. Changes in angiotensin-(1-7)
      have been proposed to be involved in the mechanism of action of ACE inhibition
      (ACEi). In particular, an altered balance between angiotensin II and angiotensin
      (1-7) might be involved. A shift in sodium status modifies the activity of the
      renin-angiotensin-aldosterone system and the effects of ACEi, but its effects on
      angiotensin-(1-7) are unknown. We therefore studied the effect of a shift in
      sodium intake on angiotensin-(1-7), during placebo and ACEi. METHODS: A double
      blind, placebo-controlled study was conducted in 17 healthy men. The subjects
      were studied for two 2-week periods: 20 mg/day enalapril and placebo. The first
      week of each period they used a 50 mmol Na+ diet [low sodium (LS)], the second
      week a 200 mmol Na+ diet. Angiotensin levels and blood pressure were measured at
      the end of each week. RESULTS: During placebo, LS intake elicited a three-fold
      rise in ang-(1-7) that paralleled the rise in other components of the renin
      angiotensin system. During ACEi LS did not affect angiotensin II, but did induce
      a clear-cut rise in angiotensin-(1-7)--to the extent that angiotensin-(1-7) was
      highest during combination of ACEi and LS. Consequently, during ACEi LS shifted
      the balance between angiotensin-(1-7) and angiotensin II towards angiotensin-(1
      7). CONCLUSION: The sodium status modifies levels of angiotensin-(1-7). During
      ACEi angiotensin-(1-7) is still subject to stimulation by sodium restriction, and
      provides opportunity for therapeutic manipulation. Exploration of this
      opportunity in patient populations may lead to strategies to improve therapeutic
      benefits of ACEi.

PMID- 15716703
TI  - Interactions of sympathetic nerves with capsaicin-sensitive sensory nerves:
      neurogenic mechanisms for phenol-induced hypertension in the rat.
AB  - BACKGROUND: Previous investigations have shown that norepinephrine is capable of
      inhibiting neurotransmission in capsaicin-sensitive sensory nerves via a
      prejunctional mechanism. The alteration in the activity of sympathetic or
      capsaicin-sensitive sensory nerves in the development of phenol-induced
      hypertension was observed separately in rats. METHODS: In the present study, we
      examined interactions of adrenergic nerves with capsaicin-sensitive sensory
      nerves in phenol-induced hypertensive rats. Blood pressure, the synthesis and
      release of calcitonin gene-related peptide (CGRP) and the content of nerve growth
      factor in (NGF) arteries were determined. RESULTS: Intrarenal injection of phenol
      caused a permanent elevation of blood pressure concomitantly with a decrease in
      the concentration of CGRP in plasma, the content of CGRP in dorsal root ganglia
      and the density of CGRP-containing nerves in the mesenteric artery, and vascular
      NGF content. Chronic treatment with prazosin (an alpha1-adrenoreceptor
      antagonist, 3 mg/kg per day) failed to alter the synthesis and release of CGRP
      and vascular NGF content, even though it completely normalized blood pressure.
      However, treatment with yohimbine (an alpha2-adrenoreceptor antagonist, 5 mg/kg
      per day) significantly increased CGRP level and vascular NGF content. Combined
      administration of prazosin and yohimbine not only significantly elevated the
      synthesis and release of CGRP and arterial NGF content, but also completely
      normalized blood pressure. CONCLUSION: These results indicate that the decreased
      production and release of CGRP and reduced vascular NGF content are attributed to
      the activation of alpha2-adrenoreceptors in phenol-induced hypertensive rats.

PMID- 15716704
TI  - Depressive symptoms are associated with unhealthy lifestyles in hypertensive
      patients with the metabolic syndrome.
AB  - OBJECTIVE: Metabolic syndrome results from a complex interaction between
      lifestyle and genetic factors. Among this population, adhesion to healthy
      recommendations is a cornerstone of cardiovascular disease prevention. We
      examined the association between depression and multiple unhealthy behaviours in
      hypertensive patients with the metabolic syndrome. RESEARCH DESIGN AND METHODS:
      Eight hundred and forty consecutive hypertensive subjects with the metabolic
      syndrome were studied in our secondary-care centre. Separated scores reflecting
      unhealthy behaviours (physical inactivity, smoking and unhealthy diet) were
      combined to produce a global unhealthy lifestyle score. The Hospital Anxiety and
      Depression scale was used to assess and quantify depression. We performed a
      separate analysis for each sex. RESULTS: The prevalence of depression (13.0
      versus 7.3%, P < 0.001) was greater in women than in men. Presence of depression
      was significantly associated in both men and women with unhealthy diet (in
      particular, excessive cholesterol and total caloric intake) but also with
      decreased physical activity in men and with smoking habits in women. In both
      sexes, the global unhealthy lifestyle score, reflecting a cluster of unhealthy
      behaviours, was positively correlated with the depression score. In multivariate
      analysis, the depression score appeared in both sexes as an independent
      determinant of unhealthy lifestyle. CONCLUSIONS: Among hypertensive subjects with
      the metabolic syndrome, depressive symptoms along a continuum of severity are
      independently associated with multiple unhealthy lifestyles. This suggests that
      even minor forms of depression may impact on adhesion to health behaviours beyond
      major depressive symptoms and/or psychiatric condition.

PMID- 15716705
TI  - The impact of body mass index on pulse pressure in obesity.
AB  - OBJECTIVE: Pulse pressure, a marker of arterial vascular properties, has been
      linked to cardiovascular diseases and complications. This study examined the
      impact of excess body mass and cardiovascular disease risk factors on pulse
      pressure (PP). DESIGN: Cross-sectional and prospective study. METHODS: Baseline
      data consist of 219 obese African Americans, with mean +/- SD age of 46.8 +/-
      10.9 years enrolled in a diet and exercise program of weight reduction. A non
      invasive monitoring device was used to acquire 24 hourly ambulatory blood
      pressures. Pulse pressure was calculated as the difference between the average 24
      h systolic and diastolic blood pressure and studied as a continuous variable and
      according to quartiles. The cross-sectional association of pulse pressure with
      body mass index (BMI) was examined using multivariate linear regression and
      proportional odds models that controlled for cardiovascular disease risk factors.
      In addition, we examined prospectively, in 36 participants, the effect of weight
      loss on pulse pressure, using the Wilcoxon signed ranked test. RESULTS: At
      baseline, a 5 kg/m2 increase in BMI was independently associated with a 35% risk
      [relative risk (RR) = 1.35, confidence interval (CI) = 1.10-1.65, P < 0.01] in
      the general study population and 19% (RR = 1.19, CI = 1.07-1.56, P = 0.04) in
      obese normotensives for increasing PP by one quartile after adjustment for other
      significant variables. After 3 months of diet and exercise intervention, BMI
      decreased by an average of 10.6% (P < 0.01) and resulted in an 8.8% (P < 0.01)
      reduction in PP. CONCLUSIONS: In the context of obesity, increasing BMI is
      independently associated with decreasing arterial compliance, as reflected in PP.
      This association highlights the potential value to cardiovascular health of any
      reduction in body weight in obese individuals.

PMID- 15716706
TI  - Is plasma cardiotrophin-1 a marker of hypertensive heart disease?
AB  - OBJECTIVE: This study was designed to investigate whether plasma concentration of
      cardiotrophin-1 (CT-1), a cytokine that induces cardiomyocyte hypertrophy and
      stimulates cardiac fibroblasts, is related to hypertensive heart disease, as
      defined by the presence of echocardiographically assessed left ventricular
      hypertrophy (LVH). METHODS: The study was performed in 31 normotensive subjects
      and 111 patients with never-treated essential hypertension (54 without LVH and 57
      with LVH). Causes of LVH other than hypertension were excluded after a complete
      medical workup. A novel enzyme-linked immunosorbent assay was developed to
      measure plasma CT-1. RESULTS: Plasma CT-1 was increased (P < 0.001) in
      hypertensives compared with normotensives. The value of CT-1 was higher (P <
      0.001) in hypertensives with LVH than in hypertensives without LVH. Some 31% of
      patients without LVH exhibited values of CT-1 above the upper normal limit in
      normotensives. A direct correlation was found between CT-1 and left ventricular
      mass index (r = 0.319, P < 0.001) in all subjects. Receiver operating
      characteristic curves showed that a cutoff of 39 fmol/ml for CT-1 provided 75%
      specificity and 70% sensitivity for predicting LVH with a relative risk of 6.21
      (95% confidence interval, 2.95 to 13.09). CONCLUSIONS: These results show an
      association between LVH and the plasma concentration of CT-1 in essential
      hypertension. Although preliminary, these findings suggest that the determination
      of CT-1 may be an easy and reliable method for the initial screening and
      diagnosis of hypertensive heart disease.

PMID- 15716707
TI  - Irbesartan and atenolol improve diastolic function in patients with hypertensive
      left ventricular hypertrophy.
AB  - OBJECTIVES AND DESIGN: An abnormal diastolic filling is common in hypertensive
      left ventricular (LV) hypertrophy, a condition that may lead to heart failure and
      death. The renin-angiotensin-aldosterone system has been implicated in the
      development of LV hypertrophy. This study examines the effects of 48 weeks of
      double-blind treatment with the AT1 receptor blocker irbesartan and the beta
      blocker atenolol on diastolic function. METHODS: Diastolic function was evaluated
      in 115 hypertensive patients with LV hypertrophy by Doppler echocardiography
      mitral inflow velocities calculated from the peak of early (E) and peak of late
      (A) diastolic velocities (E/A ratio), the E-wave deceleration time, the
      isovolumic relaxation time, the pulmonary venous flow velocity, and by the
      atrioventricular valve plane displacement method. RESULTS: By similar reductions
      in blood pressure both groups progressively reduced the LV mass index, with a
      greater reduction in the irbesartan group (P = 0.024). Diastolic function was
      improved similarly by irbesartan and atenolol; for example, the E/A ratio by 12
      and 14% (P = 0.022 and P < 0.001), and the pulmonary venous flow velocity by 10
      and 7% (P = 0.036 and P = 0.001), respectively. The isovolumic relaxation time
      was improved by irbesartan (P = 0.040) only, and was related to changes in LV
      geometry (P < 0.001). For atenolol, improvement in diastolic function was
      associated only with the reduction in blood pressure (P = 0.048). An improvement
      in diastolic function appeared greater in concentric LV hypertrophy than in
      eccentric LV hypertrophy. CONCLUSIONS: Treatment based on atenolol or irbesartan
      improves diastolic function in patients with hypertensive LV hypertrophy to the
      same degree, but through different mechanisms.

PMID- 15716708
TI  - Effect of long-acting nifedipine on mortality and cardiovascular morbidity in
      patients with symptomatic stable angina and hypertension: the ACTION trial.
AB  - OBJECTIVE: To examine the effects of nifedipine GITS on clinical outcome in
      patients with concurrent stable angina and hypertension. METHODS: Data from the
      double-blind placebo-controlled ACTION trial was stratified for hypertension
      (blood pressure > or = 140/90 mmHg), at baseline. RESULTS: A total of 52% of 7665
      ACTION patients were hypertensive. Some 80% were on a beta blocker; hypertensives
      were more often treated with other blood pressure-lowering drugs. Mean baseline
      blood pressure was 122/74 mmHg among normotensives and 151/85 mmHg among
      hypertensives. Follow-up blood pressures were reduced by nifedipine (P < 0.001)
      on the average by 3.9/2.4 and 6.6/3.5 mmHg among normotensives and hypertensives,
      respectively. Nifedipine GITS significantly (P < 0.05) reduced the combined
      incidence of all-cause mortality, myocardial infarction, refractory angina, heart
      failure, stroke and peripheral revascularization by 13% in hypertensives only.
      Nifedipine significantly reduced the incidence of any stroke or transient
      ischemic attack by almost 30% in both subgroups and the need for coronary
      angiography by 21% in normotensives and 16% in hypertensives. Among
      hypertensives, the incidence of new overt heart failure was significantly reduced
      by 38% and of debilitating stroke by 33%. Among normotensives, the need for
      coronary bypass grafting was significantly reduced by 32%. Nifedipine did not
      affect all-cause death, cardiovascular death and myocardial infarction in either
      normo- or hypertensives, but increased the need for peripheral revascularization.
      CONCLUSION: The salutary effects of the addition of nifedipine GITS to the basic
      regimen of patients with concurrent stable symptomatic coronary artery disease
      and hypertension emphasize the need for blood pressure control.

PMID- 15716709
TI  - CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot
      Trial: rationale and design.
AB  - RATIONALE: High and low blood pressure (BP) levels are common following acute
      stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly
      20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours
      of ictus, both conditions being associated with an adverse prognosis. At present,
      the optimum management of blood pressure in the immediate post-stroke period is
      unclear. OBJECTIVE: The primary aim of the Controlling Hypertension and
      Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether
      hypertension and relative hypotension, manipulated therapeutically in the first
      24 h following acute stroke, affects short-term outcome measures. DESIGN: The
      CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo
      controlled, titrated dose trial. SETTING: Acute stroke and medical units in
      teaching and district general hospitals, in the UK. PATIENTS: The CHHIPS Pilot
      Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed
      by brain imaging, who have no compelling indication or contraindication for BP
      manipulation. STUDY OUTCOMES: The primary outcome measure will be the effects of
      acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor
      therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post
      stroke. Secondary outcome measures will include the influence of therapy on early
      neurological deterioration, the effectiveness of treatment in manipulating BP
      levels, the influence of time to treatment and stroke type on response and a cost
      effectiveness analysis.

PMID- 15716710
TI  - Transforming growth factor beta1 and additional renoprotective effect of
      combination ACE inhibitor and angiotensin II receptor blocker in hypertensive
      subjects with minor renal abnormalities: a 24-week randomized controlled trial.
AB  - OBJECTIVE: To verify the benefit of renin-angiotensin system blockade in
      hypertension, the effects of 24 weeks' losartan and ramipril treatment, both
      alone and in combination, on urinary albumin excretion (UAE) and circulating
      transforming growth factor beta1 (TGF beta1) have been evaluated in hypertensive
      subjects with minor renal abnormalities. DESIGN AND METHODS: Fifty-one patients
      with stage 1 and 2 essential hypertension and with UAE > or = 20 mg/24 h but with
      maintained renal function have been included. After a 4-week run-in with placebo
      administration, a randomized double-blind, three-arm double-dummy trial was used.
      All the hypertensives (HT) were allocated randomly to three treatment arms (17
      patients for each group) and they were single-matched for age, gender, body mass
      index (BMI), systolic and diastolic blood pressure. Active treatment consisted of
      losartan (50 mg/day), ramipril (5 mg/day) and combined (losartan 50 mg/day plus
      ramipril 5 mg/day) for 24 weeks. Hydrochlorothiazide 12.5 mg/day was added in HT
      patients with uncontrolled blood pressure (> or = 140/90 mmHg) during the active
      treatment period. In all patients UAE, by immunonephelometric assay; circulating
      TGF beta1 by a solid-phase specific sandwich enzyme-linked immunosorbent assay
      (ELISA); and blood urea nitrogen (BUN), creatinine and creatinine clearance and
      potassium, by routine laboratory methods, were determined after placebo treatment
      and 24 weeks follow-up. RESULTS: The three treatment groups were comparable for
      gender, age, BMI, blood pressure, UAE and renal function measurements. During the
      active treatment period it was necessary to add hydrochlorothiazide in five
      patients--two each of the losartan and ramipril groups and one of the combined
      group. At the end of treatment, significant (P < 0.05) reductions in systolic,
      diastolic and mean blood pressure, UAE and TGF beta1 levels were observed in all
      the groups. No change in renal function measurements were observed. The absolute
      and percentage reduction in UAE and TGF beta1 were significantly higher in the
      combined group than in the losartan or ramipril groups. No significant changes in
      absolute and percentage reduction of systolic, diastolic and mean blood pressure
      were found. All treatment regimens were well tolerated with few and transient
      side-effects. CONCLUSION: These data indicate an additional renoprotective effect
      of dual blockade of the renin-angiotensin system (RAS) in hypertensive patients
      with minor renal abnormalities. In addition, the contemporaneus and marked
      decrease in TGF beta1 and UAE levels in hypertensives treated with combined
      therapy might indicate the presence of a subset of subjects who may benefit from
      complete RAS blockade.

PMID- 15716711
TI  - NADPH oxidase, superoxide overproduction and nitric oxide bioavailability in
      essential hypertension.

PMID- 15716712
TI  - Diuretics and new onset diabetes: is it a problem?

PMID- 15716714
TI  - Increased pulse wave velocity is not associated with elevated augmentation index
      in patients with diabetes.

PMID- 15716754
TI  - Diagnosis and treatment of iatrogenic femoral artery pseudoaneurysms.
AB  - Color Doppler is the procedure of choice for the diagnosis of iatrogenic femoral
      artery pseudoaneurysms. Although surgery is still necessary in a limited number
      of patients, most can be treated with ultrasound-guided thrombin injection.
      Success exceeds 90% and complications are much lower than surgery. Although rare,
      the major complication is embolization into the femoral artery. This can be
      minimized by using as little thrombin as possible, and by avoiding small
      pseudoaneurysms with short necks.

PMID- 15716755
TI  - Ultrasound guided biopsy: what's new?
AB  - Ultrasound guided intervention has become the preferred method to diagnose
      primary neoplasms and suspected metastatic disease. With developments in
      technology and changes in practice patterns, the types of referrals for
      ultrasound guided intervention will evolve. The purpose of this review is to
      highlight a variety of new or relatively new aspects of image guided biopsy and
      to focus on areas of growth.

PMID- 15716756
TI  - Pelvic ultrasound in the postabortion and postpartum patient.
AB  - Ultrasound is generally the first imaging method employed when complications are
      suspected in the pelvis during the postpartum or postabortion period. Much of
      focus in this regard is in patients with abnormal vaginal bleeding, where one
      generally wants to know if there are retained products of conception. While
      ultrasound plays a major role in assessing these problems, there is a lack of
      consensus on the best sonographic features to use. We will review the ultrasound
      features that may be useful to identify retained products of conception and will
      also focus on the overlap of normal and abnormal findings in such patients.
      Further, we will discuss other issues in the postpartum patient, such as
      complications unique to the post cesarean-section patient, unusual causes of
      vaginal bleeding, uterine rupture, uterine arteriovenous malformations, and
      ovarian vein thrombosis.

PMID- 15716757
TI  - The sonographic features of papillary thyroid carcinomas: pictorial essay.
AB  - Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy in
      children and adults, with an incidence of 22,000 cases per year in the United
      States. Differentiating PTC from more frequently occurring benign thyroid nodules
      has proved challenging as there may be significant overlap in their clinical
      presentation and sonographic appearance. That said, high-resolution ultrasound
      provides a safe and affordable way of identifying and characterizing thyroid
      nodules and guiding percutaneous biopsies. Although no single sonographic feature
      is pathognomonic for PTC, certain features should raise suspicion and the
      combination of several features may be even more suggestive. In this pictorial
      essay, we describe the high-resolution sonographic features of pathologically
      proven PTCs. The nodule number, echo texture, internal architecture,
      calcifications, margins, contours, vascularity, and lymph nodes are considered.
      While the classic sonographic description of PTC is a solitary, hypoechoic solid
      nodule with microcalcifications and intrinsic vascularity, in practice, PTC may
      manifest with a myriad of sonographic appearances making biopsy necessary for a
      definitive diagnosis.

PMID- 15716780
TI  - Using our senses in wound care.

PMID- 15716781
TI  - Age-old therapy gets new approval.

PMID- 15716788
TI  - Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and
      neuroprotectins.
AB  - PURPOSE OF REVIEW: It is well known that arachidonic acid is the precursor to
      potent mediators. Many clinical studies suggest that omega-3 polyunsaturated
      fatty acids such as eicosapentaenoic acid and docosahexaenoic acid have
      beneficial actions in human diseases. The molecular basis of these actions
      remains of interest. RECENT FINDINGS: These demonstrate that eicosapentaenoic
      acid and docosahexaenoic acid are precursors to potent (nM range) bioactive
      mediators that possess both anti-inflammatory and protective properties. These
      mediators were coined resolvins, docosatrienes, and protectins as general
      classes, since each possesses unique chemical structures that are features of the
      new chemical classes and are biosynthesized by new pathways. Resolvins,
      discovered first, were identified during the resolution phase of acute
      inflammation; hence the term resolution interaction products, because they are
      also biosynthesized by human cells via cell-cell interactions. Docosatrienes
      contain conjugated triene structures generated from docosahexaenoic acid as a
      defining feature. The protectins comprise docosatrienes and resolvins of the D
      series that are both neuroprotective and anti-inflammatory. Aspirin impacts on
      these new pathways by triggering formation of their epimers (i.e. R isomers).
      SUMMARY: In view of the many beneficial actions attributed to omega-3 dietary
      supplementation, identification of novel potent mediators from omega-3 that are
      both anti-inflammatory and protective may have wide implications.

PMID- 15716789
TI  - Phospholipid mediators in the vessel wall: involvement in atherosclerosis.
AB  - PURPOSE OF REVIEW: This review provides a brief update on the involvement of
      major phospholipid mediators, with the emphasis on platelet-activating factor and
      its analogues generated upon the oxidation of lipoproteins in vascular pathology,
      including atherogenesis. RECENT FINDINGS: Phospholipid mediators are produced
      during inflammation by various enzymes, mostly from pre-existing membrane
      phospholipids, and trigger cellular signaling via G-coupled receptors. A short
      description of lysophosphatidic acid, lysophosphocholine and sphingosine-1
      phosphate receptors and their actions is given, but attention is focused mainly
      on platelet-activating factor and its analogues. The majority of these mediators
      participate in leukocyte adhesiveness to the endothelium, leukocyte
      transmigration into the vessel wall and the subsequent formation of various
      chemokines leading to foam cell formation and smooth muscle cell proliferation
      and dedifferentiation. Platelet-activating factor and platelet-activating factor
      like phospholipids are degraded in plasma by the lipoprotein-bound enzyme of
      myeloid origin, PAF-acetylhydrolase, also known as LDL-PLA2. Although the
      overexpression of PAF-acetylhydrolase shows marked anti-atherogenic properties in
      animal models, epidemiological data in the Caucasian population have demonstrated
      that its level might be a risk factor for cardiovascular disease. Recent genetic
      studies have shown, however, that the A379V polymorphism of this gene,
      responsible for slightly higher enzymatic activity, exerts a protective effect,
      probably by modifying the enzyme function towards a less atherogenic form.
      SUMMARY: Phospholipid-borne mediators are certainly key players in inflammation
      and thus in atherosclerosis. The generation of such biologically active molecules
      is possibly dependent on nutritional habits and the availability of antioxidants,
      including enzymes protective against oxidative damage, including PAF
      acetylhydrolase.

PMID- 15716790
TI  - Vitamin E: absorption, plasma transport and cell uptake.
AB  - PURPOSE OF REVIEW: Large-scale clinical trials have failed to demonstrate a
      benefit for vitamin E supplementation in cardiovascular prevention. This
      contrasts with previous epidemiological studies indicating that individuals with
      high vitamin E status benefit from protection against chronic illnesses,
      including cardiovascular diseases. These conflicting results suggest that the
      metabolism of supplemental versus naturally delivered vitamin E and their
      potential roles, other than a potent antioxidant action, are not fully
      understood. The purpose of this review is to provide an update on current
      knowledge on the intestinal absorption of vitamin E, its plasma transport and its
      supply to cells. The review will also discuss the intravascular metabolism of
      intravenously delivered vitamin E. RECENT FINDINGS: Although the luminal
      digestion of vitamin E is fairly well understood, several pathways regulating net
      vitamin E absorption remain to be elucidated. In several cell types, cholesterol
      and vitamin E share common mechanisms for cellular uptake (scavenger receptor B
      type I and LDL receptors) and efflux (ABCA1 transporters). The role of specific
      binding proteins in alpha-tocopherol intracellular trafficking is increasingly
      being understood, leading to new insights into the non-antioxidant functions of
      vitamin E. SUMMARY: Substantial progress has been made in characterizing the
      plasma transport of vitamin E and its delivery to cells. Mechanisms regulating
      the balance between the cellular uptake and efflux of vitamin E are under
      investigation. Vitamin E is not only an antioxidant but may also modulate
      pathways of cell signalling and gene expression. The translation of this new
      knowledge into clinical studies will help define future indications for vitamin E
      supplementation.

PMID- 15716791
TI  - Oxidation, lipoproteins, and atherosclerosis: which is wrong, the antioxidants or
      the theory?
AB  - PURPOSE OF REVIEW: Paradoxically, many well-established components of the heart
      healthy lifestyle are pro-oxidant, including polyunsaturated fat and moderate
      alcohol consumption. Moreover, antioxidant supplements have failed to decrease
      cardiovascular risk in extensive human clinical trials to date. Recent progress
      in understanding the roles of oxidants in regulating VLDL secretion and as
      essential signaling molecules supports the concept that oxidation may be
      beneficial in certain circumstances but damaging in others. We summarize recent
      data on the roles played by oxidative metabolism in different tissues and
      pathways, and address whether it is currently advisable to use antioxidant
      supplements to reduce cardiovascular risk. RECENT FINDINGS: Our recent study
      reported that in liver cells, polyunsaturated fatty acids increased reactive
      oxygen species, which in turn lowered the secretion of the atherogenic
      lipoprotein, VLDL, in vitro and in vivo. Antioxidant treatments prevented VLDL
      lowering effects of polyunsaturated fatty acids in vitro, suggesting that
      supplemental antioxidants could either raise apolipoprotein-B-lipoprotein plasma
      levels in vivo, or impair the response to lipid-lowering therapies. The failure
      of antioxidants to decrease cardiovascular disease risk in many trials is also
      discussed in the context of current models for atherosclerosis progression and
      regression. SUMMARY: Oxidation includes distinct biochemical reactions, and it is
      overly simplistic to lump them into a unitary process that affects all cell types
      and metabolic pathways adversely. Guidelines for diet should adhere closely to
      what has been clinically proved, and by this standard there is no basis to
      recommend antioxidant use, beyond what is inherent to the 'heart healthy' diet in
      order to benefit cardiovascular health.

PMID- 15716792
TI  - Current understanding of the metabolism and biological actions of HDL.
AB  - PURPOSE OF REVIEW: A low concentration of HDL-cholesterol is an important risk
      factor for coronary heart disease. The purpose of this review is to summarize the
      novel functions of HDL that may protect not only from atherosclerosis, but also
      from inflammation-induced organ damage. RECENT FINDINGS: HDL interacts with
      several cellular receptors and lipid transporters. The interactions of HDL or
      apolipoprotein A-I with the scavenger receptor BI or adenosine triphosphate
      binding cassette transporters A1, G1 and G4 induce cholesterol efflux.
      Apolipoproteins and enzymes carried by HDL exert antioxidative functions. Some
      oxidative modifications of apolipoprotein A-I, for example of tyrosine residues,
      may however interfere with anti-atherosclerotic activities. The interactions of
      HDL and lysosphingolipids therein with scavenger receptor BI and sphingolipid
      receptors, respectively, elicit signals activating the protein kinase Akt, which
      in turn is a regulator of apoptosis in beta, endothelial and smooth muscle cells
      as well as a regulator of nitric oxide production and adhesion molecule
      expression in endothelial cells. Other signal transduction cascades are also
      elicited by HDL, some of which induce cholesterol efflux or activate mitogen
      activated protein kinases. SUMMARY: Properties with respect to cytokine
      production, lipid oxidation, cholesterol efflux and reverse cholesterol transport
      make HDL a protective agent and thus an interesting therapeutic target in
      atherosclerosis and inflammation-induced organ damage.

PMID- 15716793
TI  - Is there a case for n-3 fatty acid supplementation in cystic fibrosis?
AB  - PURPOSE OF REVIEW: This review evaluates our current knowledge on the association
      of fatty acid abnormalities in cystic fibrosis with the disease process, and
      makes a case for a well-designed clinical trial to evaluate the clinical efficacy
      of long chain n-3 fatty acids. RECENT FINDINGS: It has long been known that
      cystic fibrosis patients exhibit fatty acid abnormalities, but these have not
      been well investigated in tissues affected by the disease. Recent studies have
      demonstrated that such tissues do indeed show abnormalities in the proportions of
      linoleic, arachidonic and docosahexaenoic acids, and have demonstrated
      alterations in fatty acid and phospholipid metabolism in cystic fibrosis. Work in
      other areas has identified novel anti-inflammatory actions of long chain n-3
      fatty acids that might be relevant to cystic fibrosis. A recent systematic review
      of fish oil supplementation in cystic fibrosis did not allow firm conclusions to
      be drawn, but suggested that there may be some benefits. SUMMARY: The restoration
      of abnormal fatty acid profiles may be beneficial in cystic fibrosis, but this
      approach has not been evaluated in studies with a suitable design to permit firm
      conclusions to be drawn. There is a need for a long-term randomized controlled
      study to evaluate the therapeutic benefit of fish oil supplementation in cystic
      fibrosis.

PMID- 15716794
TI  - N-3 fatty acids and pregnancy outcomes.
AB  - PURPOSE OF REVIEW: To discuss new data from the literature on the relationship
      between the supply of n-3 polyunsaturated fatty acids during pregnancy and
      pregnancy outcomes, evaluated as the fatty acid composition of blood and breast
      milk, fetal and infantile development and maternal health. RECENT FINDINGS:
      Supplementation of alpha-linolenic acid in high doses or docosahexaenoic acid in
      low doses did not result in a significant enhancement of the blood
      docosahexaenoic acid status of the offspring. In contrast, supplementation of
      docosahexaenoic acid in relatively high doses led to significant increases in
      infantile docosahexaenoic acid values and to a significant enhancement of breast
      milk docosahexaenoic acid content. Electroretinogram data obtained during the
      first week of life and pattern-reversal visual evoked potentials investigated at
      50 and 66 weeks postconception were significantly associated with the
      docosahexaenoic acid status of the infant at birth. Children whose mothers
      received docosahexaenoic acid supplementation during pregnancy and lactation
      scored better in mental processing tests carried out at 4 years than children
      whose mothers received placebo. SUMMARY: Beneficial health outcomes are more
      likely to result from supplementation with docosahexaenoic acid itself, rather
      than its precursor alpha-linolenic acid. Trials have shown that a higher maternal
      docosahexaenoic acid intake during pregnancy may be favourable for the visual and
      cognitive development of the offspring. The significant positive association
      between maternal docosahexaenoic acid intake during pregnancy and the children's
      mental processing scores at 4 years suggest that optimization of the
      docosahexaenoic acid status of expectant women may offer long-term developmental
      benefits to their children.

PMID- 15716795
TI  - Current concepts in nutrition.

PMID- 15716796
TI  - Guidelines for nutritional support in intensive care unit patients: a critical
      analysis.
AB  - PURPOSE OF REVIEW: Guidelines are supposed to be helpful in clinical practice.
      Guidelines are also supposed to rest upon the evidence that there is. In the
      field of clinical nutrition the problem is that many clinical trials are not
      conclusive because they are underpowered and sometimes have an inferior design.
      RECENT FINDINGS: The publication of the Canadian guidelines one year ago
      initiated a lively debate. The Canadian guidelines used meta-analysis as a tool
      to review the literature. This resulted in both a sound evaluation of studies as
      well as some controversial recommendations. The Canadian guidelines are here put
      in a perspective in which the older type of guidelines are compared, and some of
      the points of recommendation are scrutinized. SUMMARY: What all guidelines agree
      upon is the shortage of solid knowledge, the conviction that complications
      related to nutritional therapy in the intensive care unit are not acceptable, and
      that enteral nutrition is preferable if it can be given without risk. Beyond
      that, many controversies remain and the need for high quality prospective studies
      must be emphasized. In addition, such studies must address the clinically
      important questions that the guidelines try to answer.

PMID- 15716797
TI  - Meta-analyses: what they can and cannot tell us about clinical research.
AB  - PURPOSE OF REVIEW: The number of published clinical trials has increased
      exponentially over the past few decades. The majority of clinical research
      questions has been addressed by several small or moderately sized trials.
      Statisticians have developed guidelines for meta-analyses, which provide
      objective quantitative reviews to lighten the burden of clinicians who seek to
      keep themselves current in one or more areas of clinical investigation. The
      purpose of this review is to illustrate how to read critically a meta-analysis of
      nutrition support in critically ill patients. RECENT FINDINGS: Summary evidence
      based on a meta-analysis is observational, even though the individual elements of
      the meta-analysis are clinical trials. The level of evidence from a meta-analysis
      is thus similar to that derived from a case series or a cohort, with the
      stipulation that the 'subjects' are clinical trials instead of individuals. The
      effects of the combination of parenteral and enteral nutrition on mortality and
      infection rates in critically ill patients have been compared with enteral
      nutrition alone. Meta-analysis results show non-significant reductions in
      mortality and infectious complications favoring enteral nutrition. In patients
      with acute pancreatitis, the summary effects of parenteral versus enteral
      nutrition on the infection rate indicate a significant reduction in risk favoring
      enteral nutrition. SUMMARY: An interpretation of meta-analysis summary results is
      put in perspective with underlying medical assumptions. This critical review
      indicates what issues a meta-analysis can and cannot address.

PMID- 15716798
TI  - Fatty liver in the intensive care unit.
AB  - PURPOSE OF REVIEW: Non-alcoholic steatohepatitis is a liver disease characterized
      by steatosis and steatohepatitis in subjects whose alcohol consumption is
      negligible. The primary form is associated with insulin resistance whereas
      secondary non-alcoholic steatohepatitis occurs notably during total parenteral
      nutrition or in patients in the intensive care unit. This review is mainly
      focused on recent developments in the understanding of the pathogenesis of this
      disease. RECENT FINDING: Pathogenesis involves the direct role of fatty acids in
      liver injury, oxidative stress, cytokines, genetic susceptibility or
      mitochondrial dysfunction. An increased delivery of free fatty acids to the liver
      contributes to the first hit, originating liver steatosis. The process may
      undergo a second hit, characterized by inflammation and hepatocellular
      degeneration. Mitochondrial dysfunction plays a key role by leading to abnormal
      generation of reactive oxygen species, which cause lipid peroxidation. The
      peroxidation products and cytokines favor progression from steatohepatitis to
      fibrosis. Fatty liver disease may also be encountered in the intensive care unit
      in patients receiving parenteral nutrition. However, an adapted glucose-lipid
      ratio as source of non-protein calories prevents the development of fatty liver.
      Moreover, recent evidence suggests the importance of the type of lipid infused
      (structured lipid emulsion or fish oils). The acute phase response associated
      with severe disease can also lead to the development of fatty liver in spite of
      adequate nutritional support. SUMMARY: The pathogenesis of non-alcoholic
      steatohepatitis is multifactorial, but there is growing evidence that
      mitochondrial dysfunction always plays a key role. Adapted nutrition may prevent
      in part fatty liver in the intensive care unit.

PMID- 15716799
TI  - Hypocaloric feeding of obese patients in the intensive care unit.
AB  - PURPOSE OF REVIEW: Given the increased awareness of the detrimental complications
      of overfeeding, particularly hyperglycemia, the safety and efficacy of
      specialized nutritional support for the critically ill obese patient is of major
      concern. The intent of this review is to provide the scientific foundation,
      supporting and conflicting literature, for the implementation of hypocaloric,
      high-protein specialized nutritional support for acutely ill, hospitalized
      patients with obesity. RECENT FINDINGS: Similar anabolic equivalencies can be
      achieved with hypocaloric, high-protein nutritional support compared with a more
      traditional higher calorie, lower protein regimen. The provision of additional
      calories worsens hyperglycemia, results in a further accumulation of fat mass,
      and increases the potential for overfeeding without significant net protein
      anabolism gain. SUMMARY: The current literature indicates that hypocaloric, high
      protein enteral or parenteral nutrition is promising as the standard of practice
      for the metabolic support of the critically ill obese patient. The achievement of
      net protein anabolism and the avoidance of overfeeding complications are the
      primary goals, with fat weight loss a welcome secondary benefit.

PMID- 15716800
TI  - Some interactions between gastrointestinal function and fluid and electrolyte
      homeostasis.
AB  - PURPOSE OF REVIEW: The gastrointestinal tract plays an important role in the
      maintenance of fluid and electrolyte balance, and its diseases cause disturbances
      in that balance. Conversely, fluid and electrolyte disorders may disturb
      gastrointestinal function. The purpose of this review is to highlight some recent
      literature describing these interactions against a background of fluid and
      electrolyte physiology in normal and disease states. RECENT FINDINGS:
      Gastrointestinal disease is the most common cause of fluid and electrolyte
      disturbance, and this can usually be corrected by the oral route, although
      parenteral replacement is sometimes required. The use of self-administered
      subcutaneous fluid and electrolyte administration at home is described. Reduced
      microcirculatory perfusion as a result of hypovolaemia or a rise in blood
      viscosity after packed cell transfusion may precipitate gut necrosis,
      particularly during enteral feeding. Positive salt and water balance
      postoperatively of as little as 3 l impairs gastrointestinal function and
      increases complications. Other states of salt and water retention may have
      similar effects, although further research is needed to define this. SUMMARY: The
      role of the gastrointestinal tract in controlling fluid and electrolyte balance
      is underestimated. Conversely, the effect of fluid and electrolyte imbalance on
      gastrointestinal function is apparent, but requires more research.

PMID- 15716801
TI  - The impact of stress and nutrition on bacterial-host interactions at the
      intestinal epithelial surface.
AB  - PURPOSE OF REVIEW: Most literature that examines gut barrier function focuses on
      alterations in bacterial flora, changes in mucosal epithelium, or the integrity
      of the mucosal defenses. This review examines new concepts on the interaction
      between bacteria and the host, the complex relationships that serve to benefit
      both in times of health, and the alterations and responses that occur during
      illness. RECENT FINDINGS: Recent work has demonstrated a more complex
      relationship between bacteria and barrier integrity and between bacteria
      themselves, which creates a symbiotic relationship beneficial to both host and
      flora. Host responses alter this balance, inducing changes in bacteria that may
      be deleterious to both. SUMMARY: With a better understanding of the bacteria-host
      interactions in health and the alterations induced by critical illness, new
      therapies that improve the environment of both may lead to better recovery rates
      in intensive care unit patients.

PMID- 15716803
TI  - Bibliography. Current world literature. Lipid metabolism and therapy.

PMID- 15716802
TI  - The role of the dietitian in the intensive care unit.
AB  - PURPOSE OF REVIEW: The role of the intensive care unit registered dietitian has
      evolved over the past few years to become a vital component of the intensivist
      led multidisciplinary intensive care unit team. The purpose of this review is to
      define the level of clinical practice and skill set of the intensive care unit
      dietitian, which defines them as a clinician, educator and researcher worthy to
      practice alongside their colleagues on the intensive care unit team. RECENT
      FINDINGS: An intensive care unit registered dietitian must be a dedicated
      professional with advanced training in critical care nutrition, the ability to
      read critically and evaluate new literature, a willingness to think 'outside the
      box', the fortitude to be an active participant in the intensive care unit team,
      the aptitude to educate colleagues and students from all disciplines, and the
      desire to participate in clinical research. Intensive care unit registered
      dietitians have published research concerning the nutritional assessment of the
      critically ill patient, the route of nutritional support, nutritional access,
      fluid and electrolyte issues, speciality enteral products, and optimal blood
      glucose control. They continue to attain skills and knowledge to extend their
      scope of practice and improve the quality of care in the intensive care unit.
      Recent guidelines adapted to the nutritional care of critically ill patients have
      been published for guidance. SUMMARY: The scope of practice of intensive care
      dietitians defines them as clinicians, educators and researchers. Their skill set
      is a unique and vital component of the intensivist-led multidisciplinary
      intensive care unit team.

PMID- 15716804
TI  - Hepatitis a vaccination coverage among children aged 24-35 months--United States,
      2003.
AB  - Hepatitis A vaccine was first licensed in the United States in 1995. In 1996, the
      Advisory Committee on Immunization Practices (ACIP) recommended vaccination of
      children aged >/=24 months in populations with the highest incidence of hepatitis
      A (e.g., American Indian/Alaska Native [AI/AN], Asian/Pacific Islander, and
      selected Hispanic and religious communities). In 1999, these guidelines were
      expanded to recommend routine vaccination for children residing in 11 states
      where average annual hepatitis A incidence during 1987-1997 was at least 20 per
      100,000 population (twice the national average) and to consider routine
      vaccination for children in six states where average annual incidence was 10-20
      per 100,000 population. This report is the first national analysis of hepatitis A
      vaccination coverage among children. The results indicate that, in 2003,
      vaccination coverage levels with at least 1 dose of hepatitis A vaccine for
      children aged 24-35 months varied from 6.4% to 72.7% in areas where routine
      vaccination is recommended. In addition, hepatitis A vaccination coverage rates
      for children aged 24-35 months are lower than overall rates for other vaccines
      recommended for children. Sustaining and improving vaccination coverage among
      young children is needed to ensure continued declines in hepatitis A incidence in
      the United States.

PMID- 15716805
TI  - Nonfatal motor-vehicle-related backover injuries among children--United States,
      2001-2003.
AB  - Motor-vehicle (MV)-related backovers (i.e., incidents involving children being
      struck by or rolled over by a vehicle moving in reverse) represent a risk for
      severe injury and death. To characterize nonfatal MV backover injuries among
      children, CDC analyzed data from the National Electronic Injury Surveillance
      System All Injury Program (NEISS-AIP). This report summarizes the results of that
      analysis, which determined that, during 2001-2003, an estimated 7,475 children
      (2,492 per year) aged 1-14 years were treated for nonfatal MV backover injuries
      in U.S. hospital emergency departments (EDs). The report also highlights
      differences in type and severity of MV backover injuries by age and underscores
      the need for effective interventions. NEISS-AIP data can increase the
      understanding of nonfatal MV backover injuries and help guide the development of
      prevention strategies, such as education, environmental improvements, and changes
      in vehicle design, that might help reduce these injuries among children.

PMID- 15716806
TI  - Measuring exposure to an elemental mercury spill--Dakota County, Minnesota, 2004.
AB  - Elemental mercury spills can cause contamination of neighborhoods and homes and
      result in neurologic and kidney disorders in exposed persons who inhale mercury
      vapors. Often, however, difficulties exist in determining the magnitude of
      exposure and effectiveness of decontamination or in recognizing that reexposure
      has occurred. This report summarizes the response to an elemental mercury
      exposure that resulted in the decontamination of 48 persons and the subsequent
      analysis of blood and urine samples from 14 exposed youths aged 6-16 years. Data
      from these analyses suggest that 1) blood samples are more sufficiently acquired
      and can be used to evaluate recent acute exposure and 2) use of a real-time
      mercury vapor analyzer can help public health officials determine the magnitude
      of exposures and help prevent reexposures. In addition, demolition and waste
      disposal firms and government agencies must take actions to ensure that elemental
      mercury is adequately secured before disposal.

PMID- 15716807
TI  - Tuberculosis transmission in a homeless shelter population--New York, 2000-2003.
AB  - In 2003, the incidence of tuberculosis (TB) cases in the United States declined
      for the eleventh consecutive year to a record low of 5.1 cases per 100,000
      population. In 2003, 6.3% of reported TB cases in the United States were among
      homeless persons. Compared with the general population, this group has a greater
      risk for latent TB infection (LTBI) and progression to active disease. This
      report summarizes a recent outbreak of TB and highlights the challenges of
      preventing TB among homeless persons, particularly when multiple chains of
      transmission are occurring and multiple jurisdictions are involved. The findings
      underscore the complementary role of rapid DNA genotyping in the detection of
      possible TB transmission in homeless populations. To ensure early detection of
      unsuspected TB transmission in homeless populations, health department TB-control
      programs are encouraged to use CDC's universal Mycobacterium tuberculosis rapid
      genotyping system.

PMID- 15716809
TI  - Evolving models of Geriatric Nursing care.
AB  - Outcomes of care improve when older patients are cared for by nurses with
      demonstrated competence in geriatrics and in environments that structure nursing
      care around the needs of older adults. The past twenty years has seen the
      development of a number of exciting new nursing models in the delivery of care
      for older adults. This article highlights some of these evolving models of
      nursing practice in assisted living, home care, hospitals, and nursing homes.

PMID- 15716810
TI  - A model long-term care hospice unit: care, community, and compassion.
AB  - The purpose of this study was to investigate the factors that influenced the
      quality of care of terminally ill nursing home residents on a hospice unit in a
      city and county long-term care facility. The findings disclosed that the hospice
      team had created a cultural environment in which care, community, and compassion
      were the predominant components of their philosophy of palliative care.
      Communication at all levels-among staff, family, friends, and residents-was found
      to be a core hospice value, essential to community development. The results of
      this study illustrate that exemplary palliative care can be provided when an
      interdisciplinary team is dedicated to creating an environment where the
      principles of palliative care can be fully implemented. The authors conclude that
      there is a developing role for geriatric nurses to participate in further
      defining and providing palliative care for older people in their homes,
      hospitals, nursing homes, and residential care.

PMID- 15716811
TI  - Benefits and challenges of research with the oldest old for participants and
      nurses.
AB  - The Klamath Exceptional Aging Project is a longitudinal aging study of people 85
      and over, the "oldest old," in rural Oregon. Although conducting research with
      those 85 and over can be challenging, it is increasingly more important that this
      group be included in research studies given their importance in society. Benefits
      for the oldest old participating in research include an opportunity for altruism,
      productivity, and generativity and the expression of power and control. Benefits
      for nurses conducting research with this group include gaining a unique
      understanding of the world of the elderly, the honor of being a confidante for
      them, and the opportunity to provide truly caring nursing to a vulnerable age
      group. There is also a great sense of satisfaction in adding to the knowledge
      base needed to attain successful aging.

PMID- 15716812
TI  - Facilitating interdisciplinary practice through mobile service provision to the
      rural older adult.
AB  - Reaching the older adult in the rural communities in which they reside is
      desirable in an effort to support aging in place. The Idaho State University
      (ISU) Senior HealthMobile is an innovative, interdisciplinary rural health
      outreach effort designed to meet the needs of the older adult and support healthy
      aging. Health and wellness support services are provided through mobile
      interdisciplinary teams involving students and faculty in nursing, physical
      therapy, occupational therapy, pharmacy, and dietetics, among other disciplines.
      Students and supervising faculty provide services in the ISU Senior HealthMobile,
      in the rural senior centers, and in the home, providing a unique opportunity to
      be a part of the life of the older adult in the rural community setting.
      Partnerships and collaborative linkages within the community setting support the
      enhancement of existing services in collaboration with the ISU Senior
      HealthMobile.

PMID- 15716813
TI  - The legal nurse consultant.
AB  - An abundance of new opportunities have arisen in the legal field for nurses. One
      such area of specialty practice involves the legal nurse consultant. This article
      outlines the basics of what job tasks a legal nurse consultant might undertake,
      the level of knowledge and skill required, and the various areas within the
      consultant field itself that are open.

PMID- 15716814
TI  - Wanted--committed gerontological nurse preceptors.
AB  - Good gerontological nurse preceptors can help students feel comfortable working
      with older adults. They can also provide assistance to students in narrowing the
      theory-practice gap that sometimes seems to exist. Developed in this article is
      an understanding of preceptoring students and working with them and academic
      faculty to promote positive gerontological nursing experiences.

PMID- 15716821
TI  - A quarter century of nutrition progress for older adults.

PMID- 15716822
TI  - All home care is not created equal--one view: dramatic growth in home health care
      industry creates unregulated workforce; more government oversight is needed.

PMID- 15716826
TI  - Drugs and the elderly: looking back and ahead.

PMID- 15716825
TI  - Gerontologic nurse practitioner care guidelines: Assessing and managing hearing
      deficits in the older adult.

PMID- 15716828
TI  - Oral health care delivery--preparing for the future.

PMID- 15716829
TI  - Incidence and evolution of inferior alveolar nerve lesions following lower third
      molar extraction.
AB  - OBJECTIVES: To calculate the incidence of inferior alveolar nerve (IAN) damage
      due to lower third molar extraction and to describe the evolution of IAN
      sensitivity and the prognosis of IAN damage based on preoperative data. STUDY
      DESIGN: A retrospective study of 4995 lower third molar extractions in 3513
      outpatients. RESULTS: Fifty-five extractions (1.1%) resulted in IAN impairment.
      Cox regression analysis showed age to be a risk factor for the persistence of IAN
      injury due to lower third molar extraction. The sensation recovery rate was
      higher in the first 3 months. Fifty percent of the patients showed full recovery
      after 6 months. CONCLUSIONS: Most cases of IAN impairment following lower third
      molar extraction recover within 6 months, though in some cases recovery takes
      more than 1 year. Older patients are at an increased risk of incomplete recovery
      of chin and lip sensibility after third molar extraction.

PMID- 15716830
TI  - Incidence and clinical features of delayed-onset infections after extraction of
      lower third molars.
AB  - OBJECTIVE: To describe the incidence and clinical features of delayed-onset wound
      infections after lower third molar extractions in an outpatient clinic. STUDY
      DESIGN: Retrospective forward study of 958 lower third molar extractions in the
      Oral Surgery and Implantology Department of the School of Dentistry of the
      University of Barcelona (Spain). RESULTS: Fourteen delayed-onset wound infections
      were recorded after suture removal (1.5% of the extractions). These infections
      usually developed 3-5 weeks after extraction. Half of the cases presented a
      radiolucency around the crown of the third molar. In most cases, ostectomy
      (13/14) and tooth sectioning (11/14) had been made. CONCLUSIONS: Delayed
      infections were a rare postoperative complication of lower third molars
      extractions. Nevertheless, patients should be warned that infection can still
      occur several weeks after the surgical procedure.

PMID- 15716831
TI  - Management options for dental extraction in hemophiliacs: a study of 55
      extractions (2000-2002).
AB  - OBJECTIVE: Dental extraction in hemophiliacs is associated with a high risk of
      bleeding. It requires a multidisciplinary approach and stringent protocol. The
      current trend is to simplify these protocols. In this study we review the
      efficacy of a protocol using systemic treatment--factors/dihydro-D-arginine
      vasopressin (DDAVP)--and simplified local hemostatic measures to control
      bleeding, to limit patient discomfort, and to minimize hospital length of stay.
      STUDY DESIGN: This retrospective study of 55 dental extractions was performed
      during 19 interventions in 16 patients with hemophilia A or B to assess the
      efficacy of a protocol combining general management via the injection of factor
      concentrates or DDAVP and local hemostasis using biological glue and gelatin
      packing. Compressive, hemostatic splints, which have been in use by some for many
      years, are replaced by intermittent tranexamic acid compression during the first
      3 days after surgery. RESULTS: We recorded 6 instances of postsurgical bleeding,
      4 of which occurred after the compression period. In 2 cases repetition of the
      local hemostasic measures was required along with the injection of an
      antihemophilic factor concentrate. In the other 4 cases, the patients' condition
      reverted to normal following injection of the factor concentrate and the
      reapplication of the compression. CONCLUSION: The adopted protocol produced a
      reliable outcome, limiting the duration of the hospital stay to 24 hours in most
      cases, and improving postsurgical comfort thanks to a combination of systemic
      treatment and local hemostasic measures including intermittent tranexamic acid
      compression.

PMID- 15716832
TI  - Analysis of tumor necrosis factor-alpha, interleukin-6, interleukin-1beta,
      soluble tumor necrosis factor receptors I and II, interleukin-6 soluble receptor,
      interleukin-1 soluble receptor type II, interleukin-1 receptor antagonist, and
      protein in the synovial fluid of patients with temporomandibular joint disorders.
AB  - OBJECTIVE: To measure the levels of various cytokines, cytokine receptors, and
      cytokine antagonists in the synovial fluid of patients with temporomandibular
      disorders (TMD) and to determine the correlations among these expression levels.
      STUDY DESIGN: Synovial fluid was obtained from 55 patients with TMD and from 5
      asymptomatic healthy volunteers as controls. The concentrations of tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-6, IL-1beta, soluble tumor necrosis factor
      receptors I and II (sTNFR-I and sTNFR-II), IL-6 soluble receptor (IL-6sR), IL-1
      soluble receptor type II, and IL-1 receptor antagonist were determined by enzyme
      linked immunosorbent assay. RESULTS: The concentrations of TNF-alpha, IL-6, IL
      1beta, sTNFR-I, and sTNFR-II were significantly higher in the synovial fluid of
      patients than in controls (P < .05). TNF-alpha level was positively correlated
      with those of IL-6, sTNFR-I, and sTNFR-II. In particular, there was a highly
      significant positive correlation between sTNFR-I and sTNFR-II. CONCLUSION: TNF
      and sTNFRs in the synovial fluid of patients with TMD may be important in the
      pathogenesis of these disorders.

PMID- 15716833
TI  - The influence of alendronate on bone formation after autogenous free bone
      grafting in rats.
AB  - OBJECTIVE: This study was undertaken to investigate the influence of alendronate
      on bone formation after autogenous free bone grafting in rats. STUDY DESIGN:
      Fifty-six male Wistar-Albino rats were divided into 3 groups: baseline, saline
      treated, and alendronate-treated groups, and followed up at 2, 4, and 12 weeks.
      In the femur of the rats, autogenous free bone grafts 3 mm in diameter and 2 mm
      in length were harvested with a standard trephine bur. The bone defects 3 mm in
      diameter and 2 mm in length were created 5 mm from the donor sites. Each graft
      was placed in the bone defect and stabilized by perifemoral wiring. The
      alendronate-treated rats were administered 0.25 mg/kg alendronate subcutaneously
      daily. The saline-treated rats were given daily saline solution. Serum calcium,
      phosphate, parathyroid hormone, 1,25-dihydroxyvitamin D, bone alkaline
      phosphatase (BAP), osteocalcin, and urine calcium were measured. The changes in
      the number of osteoblasts bordering active bone formation surface and osteoid and
      lamellar bone formation were evaluated to measure anabolic bone activity.
      RESULTS: Alendronate caused significant increase in serum osteocalcin and BAP
      levels biochemically and the number of osteoblasts histopathologically.
      CONCLUSION: Alendronate may be considered among therapeutic options to improve
      bone formation process in different bone remodeling cases. Further detailed
      studies should be focused on dosage- and time-dependent effects of alendronate on
      bone formation.

PMID- 15716834
TI  - Incidence and bacteriology of bacteremia associated with various oral and
      maxillofacial surgical procedures.
AB  - OBJECTIVE: The aim of this study was to determine the incidence and bacteriology
      of bacteremia associated with various oral and maxillofacial surgical procedures.
      METHODS: A total of 237 patients who underwent oral and maxillofacial surgery
      were included in this study. Blood samples were obtained for bacteriological
      examination immediately after the essential steps of the surgical procedure had
      been performed. RESULTS: Bacteremia was detected in patients who underwent
      surgery for tumor, infection and trauma, and surgical reconstruction of jaw. In
      particular, decortication for osteomyelitis and tooth extraction resulted in a
      higher incidence of bacteremia compared with other surgical procedures. The
      incidence of bacteremia was not affected by oral hygiene, gingival inflammation,
      blood loss, and duration of surgery. Furthermore, concerning tooth extraction,
      there was no statistical difference in the incidence of bacteremia with respect
      to the number of teeth extracted and the method of extraction. Extraction of
      teeth with odontogenic infection (periodontitis, periapical infection, and
      pericoronitis) did however produce a significantly increased incidence of
      bacteremia compared with infection-free teeth (P < .01). Viridans streptococci
      were the predominant group of bacteria isolated from the bacteremias. CONCLUSION:
      Oral and maxillofacial surgery involving transoral incision produces bacteremia,
      regardless of the extent and degree of surgical invasion. In particular, surgical
      procedure at infected sites is more likely to result in bacteremia compared with
      infection-free sites.

PMID- 15716835
TI  - Validity of stimulated whole saliva collection as a sialometric evaluation for
      diagnosing Sjogren's syndrome.
AB  - OBJECTIVE: The purposes were to compare the practice effect of stimulated whole
      saliva collection (SWSC) with unstimulated whole saliva collection (UWSC), and to
      investigate the validity of the tests as a criterion in the diagnosis of
      Sjogren's syndrome (SS), allowing for the practice effect. STUDY DESIGN: SWSC (n
      = 34) or UWSC (n = 27) was performed 3 times on healthy volunteers to investigate
      practice effects; then the differences among the 3 measurements were analyzed.
      For evaluating the validity of the tests, UWSC and SWSC were performed
      alternately on 28 SS patients and 34 control subjects, all of whom had had a
      practice SWSC before the actual test; then the sensitivity and specificity of
      both tests as a criterion in the diagnosis of SS were calculated. RESULTS: A
      practice effect was observed for SWSC, but not for UWSC. When an orientation
      measurement was performed before the actual SWSC, there was no statistically
      significant difference between the accuracy of SWSC and UWSC as a criterion in
      the diagnosis of SS. CONCLUSION: If an orientation measurement is performed
      before the actual measurement, SWSC can be as valid a test for sialometric
      evaluation in the diagnosis of SS as UWSC.

PMID- 15716836
TI  - Localized B-cell non-Hodgkin's lymphoma of oral cavity and maxillofacial region:
      a clinical study.
AB  - OBJECTIVE: Non-Hodgkin's lymphomas (NHL) are the third most common group of
      malignant lesions in the oral cavity and maxillofacial region. Most such
      lymphomas have been shown to be predominantly of B-lineage. The purpose of the
      present study is to analyze the clinical signs and symptoms and the clinical
      staging of B-cell NHL of this region. STUDY DESIGN: Eighteen adults, with B-cell
      NHL manifestations of the oral cavity and maxillofacial region, were available
      for this study. The clinical stage according to the Ann Arbor system was assessed
      by history, physical, and laboratory examination. Hematoxylin and eosin--stained
      slides and paraffin blocks were available for all cases. Histologic diagnosis was
      based on the WHO classification of tumors. RESULTS: The mean age of patients at
      the time of biopsy was 64 years. At the time of the disease presentation,
      according to the Ann Arbor system, 11 patients were in stage IE, 2 patients in
      stage IIE, 2 patients in stage IIIE, 1 patient in stage IVE, and 2 patients in
      stage IV. The typical clinical appearance was a painless local mass lateral or
      bilateral. Often there is a superficial ulceration of the tumor mass. Tonsillar
      NHL was the most frequent site occurring in 8 patients followed by NHL of the
      oral cavity, of the salivary glands, and of the mandible. Grading revealed that
      most cases were high grade (11 cases), followed by the cases of low grade (5
      cases) and intermediate grade (2 cases). All the different histologic types may
      be observed, but the most frequently encountered is the diffuse large type.
      CONCLUSIONS: The B-cell NHL may involve both osseous and soft tissues of the oral
      cavity and maxillofacial region. The favored sites are tonsils, palatal mucosa
      and parotid glands. The typical clinical appearance is a painless local mass
      lateral or bilateral. Often there is a superficial ulceration of the tumor mass.
      According to the Ann Arbor system, the majority of the cases at the time of
      diagnosis are in stage I or II. Most patients have high grade disease. All the
      different histologic types may be observed, but the most frequently encountered
      is the diffuse large type.

PMID- 15716837
TI  - Human papilloma virus in oral squamous cell carcinoma in a Mexican population.
AB  - OBJECTIVE: To determine the human papilloma virus (HPV) infection in oral cancer
      and its association with smoking and drinking habits. STUDY DESIGN: A cross
      sectional study was performed; samples were collected from 51 patients with
      histological diagnosis of squamous-cell carcinoma were collected at the Instituto
      Nacional de Cancerologia in Mexico City. HPV infection was detected by polymerase
      chain reaction, and the clinical characteristics of this population were
      analyzed. RESULTS: Fifty samples out of 51 were positive for beta-globin; 21
      (42%) cases were HPV-positive, and 14/21 were positive for HPV-16. We found more
      samples positive in men than in women (71% vs 29%). No differences were observed
      between HPV-positive and -negative patients in relation to smoking and drinking
      habits (81% vs 79%). CONCLUSIONS: HPV infection was present in 42% of patients
      with oral squamous-cell carcinoma (OSCC); HPV-16 was the most frequent type,
      identified in 66.6%. Other cofactors participate in the development of OSCC,
      independent of HPV infection.

PMID- 15716838
TI  - The effects of electrostimulation on parotid saliva flow: a pilot study.
AB  - OBJECTIVE: Saliva is a critical fluid necessary for oral health. Medications,
      radiation therapy, and systemic conditions can decrease salivary function and
      increase a patient's risk for caries and other oral infections. Palliative
      management of xerostomia includes wetting agents such as ice chips and saliva
      substitutes. Systemic agents stimulate salivary flow but often have unfavorable
      side effects. All have met with limited success. The purpose of this study is to
      assess the effectiveness of transcutaneous electric nerve stimulation (TENS) as a
      means of stimulating salivary function in healthy adult subjects. STUDY DESIGN:
      Twenty-two healthy, adult subjects with no history of salivary gland disorder
      enrolled in the protocol. The TENS electrode pads were placed externally on the
      skin overlying the parotid glands. Unstimulated saliva was collected for 5
      minutes via the Carlson-Crittenden cup into preweighed vials using standardized
      collection techniques. The TENS unit was then activated and stimulated saliva
      collected for an additional 5 minutes. RESULTS: Fifteen of 22 subjects
      demonstrated increased parotid salivary flow when stimulated via the TENS unit.
      Five experienced no increase and 2 experienced a decrease. The mean unstimulated
      salivary flow rate was 0.02418 mL/min (SD 0.03432) and mean stimulated salivary
      flow rate was 0.04946 mL/min (SD 0.04328). Statistical analysis of flow rates
      utilizing the paired t test demonstrated the difference to be statistically
      significant, P < .001. In 7 subjects with 0 baseline flow, 5 continued to have no
      flow. CONCLUSIONS: The TENS unit was effective in increasing parotid gland
      salivary flow in two-thirds of healthy adult subjects. A further study in a
      cohort of patients with salivary gland disorders is warranted.

PMID- 15716839
TI  - An overview of oral frena and their association with multiple syndromic and
      nonsyndromic conditions.
AB  - The development of abnormal oral frena is an important diagnostic feature of
      several syndromic states. Five such syndromes are reviewed which include Ehlers
      Danlos syndrome, infantile hypertrophic pyloric stenosis, holoprosencephaly,
      Ellis-van Creveld syndrome, and oral-facial-digital syndrome. Each syndrome
      exhibits relatively specific frena abnormalities, ranging from multiple,
      hyperplastic, hypoplastic, or absent. 1-8 In addition to abnormal oral frena
      observed in syndromic conditions, anomalous frena are encountered without other
      associated phenotypic features of genetic or chromosomal states. 9 This paper is
      a review of the above stated frena deformities and their management.

PMID- 15716840
TI  - Myofibromatosis: a case report with a unique clinical presentation.
AB  - Myofibroma and myofibromatosis have been described under different names since
      1951. These lesions are a benign fibroblastic and myofibroblastic proliferation
      containing a biphasic presentation of spindle-shaped cells surrounding a central
      zone of less differentiated cells focally arranged in a hemangiopericytoma-like
      pattern. Classically, these lesions are described in children younger than 2,
      with two thirds present at birth, and rarely in adults. The typical clinical
      presentation shows variable growth pattern of a painless purple to pink soft
      tissue mass, often showing secondary ulceration. Controversy exists as to an
      autosomal dominant or recessive inheritance versus sporadic occurrence. Presented
      here is a unique case of myofibromatosis presenting first as a superficial scalp
      lesion at age 2, followed by other primary lesions of the right mandibular
      vestibule, right temple, and left mandibular vestibule at ages 9, 12, and 23,
      respectively. All were treated with excision, without recurrence at the primary
      site.

PMID- 15716841
TI  - Intraoral chondroid lipoma: a case report and immunohistochemical investigation.
AB  - Lipomas are common neoplasms of fat in the oral cavity. However, the diagnosis
      may be difficult for lesions exhibiting unusual histological features. This paper
      documents the first intraoral report of a chondroid lipoma. The differential
      diagnosis is discussed. It is important for practicing oral pathologists to
      recognize rare variants to ensure accurate diagnosis and appropriate treatment
      for the patient.

PMID- 15716842
TI  - Bilateral central giant cell granulomas of the mandible in an 8-year-old girl
      with Noonan syndrome (Noonan-like/multiple giant cell lesion syndrome).
AB  - We report a case of an 8-year-old girl who presented with bilateral central giant
      cell granulomas of the posterior mandible. Characteristic facial features and a
      history of pulmonary stenosis led us to suspect a diagnosis of Noonan syndrome. A
      medical geneticist confirmed this. This case report will discuss the salient
      features of this diagnosis.

PMID- 15716844
TI  - Prevalence and variations of pneumatized articular eminence: a study from Turkey.
AB  - OBJECTIVES: Pneumatized articular eminence or tubercule (PAT) is an air cell
      cavity in the zygomatic process of the temporal bone that is similar to air cells
      in the mastoid process and ethmoid bone. The purpose of this study was to
      determine the prevalence and variations of PAT among an outpatient dental clinic
      population at Ankara University, Turkey, to make a contribution to the few
      current studies about PAT. STUDY DESIGN: A total of 1006 panoramic radiographs
      were retrospectively investigated for the prevalence and radiographic features of
      PAT. Meta-analysis was done for 4 large case series in the literature and our
      case series. Furthermore, we performed Chi-square test to evaluate age, gender,
      localization, and prevalence differences among 5 case series including ours.
      RESULTS: PAT was found in 19 (1.88%) patients with a mean age of 36.6 (SD 21.06)
      years. Twelve cases (63.1%) occurred in females and 7 cases (36.9%) occurred in
      males. Bilateral PAT was found in 7 patients (36.9%). Meta-analysis of 5 large
      case series revealed a total of 6669 patients, of whom 115 had PAT (1.76%
      prevalence) occurring over an age range of 7 to 90 years. Fifty (43.47%) occurred
      in males and 65 (56.53%) occurred in females. Bilateral PAT was found in 28
      (24.34%) patients. The result of Chi-square test showed no statistically
      significant differences among the 5 studies with respect to age, gender,
      localization, and prevalence. CONCLUSIONS: Knowledge about these structures is
      helpful for the interpretation of imaging such as panoramic radiographs and
      provides valuable information to understand the spread and differential diagnosis
      of pathological entities in this region. Moreover, clinicians who are planning to
      perform temporomandibular joint surgery are advised to assess radiographic
      imaging thoroughly before the surgery to avoid intra-operative complications and
      reconstruction.

PMID- 15716843
TI  - Condylar shape analysis using panoramic radiography units and conventional
      tomography.
AB  - OBJECTIVE: The objective of this study was to compare condyle shape between
      lateral temporomandibular joint (TMJ) images from axially corrected tomography
      and 3 panoramic radiography units with TMJ-specific programs. STUDY DESIGN: The
      TMJ from a single dry human skull was imaged with multidirectional tomography and
      the following 3 panoramic radiography units: Instrumentarium OP 100, Planmeca PM
      2002 CC Proline, and Soredex Orthophos DS. A curve-fitting procedure (spline
      curves) was used to mathematically describe condyle outlines. One sample t tests
      were used to compare panoramic images against the tomograms (gold standard).
      RESULTS: A significant difference (P < .05) in condyle shape was found between
      TMJ tomography images and each of the 3 panoramic images. Images from the PM 2002
      CC Proline demonstrated the smallest shape difference (13.4%), followed by the OP
      100 (17.5%) and the Orthophos DS (24.8%). CONCLUSION: If panoramic radiography is
      to be used for the initial radiographic examination of the TMJ, practitioners
      should be aware of the potential for shape distortion of the condyle.

PMID- 15716845
TI  - Evaluation of the relationship between periapical lesions/sclerotic bone and
      general bone density as a possible gauge of general health among 80-year-olds.
AB  - OBJECTIVES: To evaluate the incidence among 80-year-olds of periapical lesions as
      detected on panoramic radiographs and to determine the relationship between
      sclerotic bone around the periapical lesions to heel bone density, body height,
      and hand-grip strength. STUDY DESIGN: Six hundred fifty-nine panoramic
      radiographs (262 males, 397 females), obtained from 80-year-old residents of
      Fukuoka Prefecture, Japan, were used for evaluation of periapical lesions. These
      findings were correlated with physical examination results to determine the
      relationship to general health. RESULTS: Of 659 panoramic radiographs, 31 (5%)
      were noted to have periapical lesions. Average size of the 31 periapical lesions
      was 6.1 +/- 2.2 mm. Of the 31 periapical lesions, 21 (68%) were accompanied by
      linear or diffuse types of sclerotic bone. Of the 21 sclerotic bones, 10 (48%)
      were of a linear type of sclerotic bone and 11 (52%) of a diffuse type of
      sclerotic bone. Of the 11 diffuse types of sclerotic bone, 10 (91%) were in the
      mandible and 1 (9%) in the maxilla. Periapical lesions in the mandible were more
      frequently accompanied by a diffuse type of sclerotic bone than those in the
      maxilla (P < .01). The hand-grip strength of those having periapical lesions,
      accompanied by a diffuse type of sclerotic bone, was stronger than those having
      no periapical lesions (P < .01) and those accompanied by a linear type of
      sclerotic bone (P < .03). However, there was no relationship between presence of
      sclerotic bone and heel bone density or body height. CONCLUSIONS: Periapical
      lesions accompanied by a diffuse type of sclerotic bone were more frequently seen
      in the mandible of 80-year-olds. To evaluate the clinical significance of
      sclerotic bone around periapical lesions in 80-year-olds, further study to
      evaluate the significance of endodontic treatment needs to be done.

PMID- 15716846
TI  - Efficacy of articaine and lidocaine in a primary intraligamentary injection
      administered with a computer-controlled local anesthetic delivery system.
AB  - OBJECTIVE: The purpose of this prospective, randomized, double-blind study was to
      compare the anesthetic efficacy of the intraligamentary injection of 4% articaine
      with 1:100,000 epinephrine and of 2% lidocaine with 1:100,000 epinephrine,
      administered with computer-controlled local anesthetic delivery system, in
      mandibular posterior teeth. STUDY DESIGN: Using a crossover design,
      intraligamentary injections of 1.4 mL of 4% articaine with 1:100,000 epinephrine
      and of 1.4 mL of 2% lidocaine with 1:100,000 epinephrine were randomly
      administered with a computer-controlled local anesthetic delivery system, in a
      double-blind manner on the mesial and distal aspects of a mandibular first molar,
      at 2 separate appointments to 51 subjects. A pulp tester was used to test for
      anesthesia, in 2-minute cycles for 60 minutes, of the mandibular first and second
      molars and second premolar. Anesthesia was considered successful when 2
      consecutive 80 readings (highest output) were obtained within 20 minutes.
      RESULTS: Successful pulpal anesthesia was obtained 86% of the time for the first
      molar using the articaine solution and 74% of the time using the lidocaine
      solution. There were no significant differences (P > .05) between the articaine
      and lidocaine solutions. The mean onset times of pulpal anesthesia for the first
      molar were 1.3 minutes with articaine solution and 2.2 minutes with lidocaine
      solution. Duration of pulpal anesthesia for the first molar was 34 minutes for
      the articaine solution and 31 minutes for the lidocaine solution. CONCLUSION: The
      efficacy of 4% articaine with 1:100,000 epinephrine was similar to the efficacy
      of 2% lidocaine with 1:100,000 epinephrine for intraligamentary injections.

PMID- 15716847
TI  - Comparison of quality of life after surgical endodontic treatment using two
      techniques: a prospective study.
AB  - OBJECTIVE: The purpose of this prospective study was to compare patient
      experience of quality of life following surgical endodontic treatment using 2
      different techniques: a technique that included the use of a dental operating
      microscope, root resection with minimal bevel and retrograde preparation with
      ultrasonic tips, and a traditional technique that included root resection with a
      45 degrees bevel and retrograde preparation by bur performed without
      magnification. STUDY DESIGN: The study consisted of 66 patients referred for
      surgical endodontic treatment. One operator (I.T.) carried out all treatment. An
      equal number of patients were assigned to each group. Group 1 was treated by the
      traditional technique without an operating microscope and Group 2 by a technique
      using an operating microscope and minimal osteotomy. All patients were given a
      questionnaire with 15 questions to evaluate their quality of life for 7 days
      postsurgery. RESULTS: On day 5, patients in Group 1 reported significantly more
      pain and took significantly more analgesics (P < .05). On days 1 and 2, patients
      in Group 2 reported significantly more difficulty in mouth opening, mastication,
      and the ability to speak (P < .05). CONCLUSION: Patients in both groups reported
      a high incidence of symptoms. The technique using the operating microscope
      provided significantly less postoperative pain, but more difficulties in mouth
      opening, mastication, and the ability to speak immediately postoperatively.

PMID- 15716848
TI  - The effect of the use of 2% chlorhexidine gel in post-space preparation on carbon
      fiber post retention.
AB  - OBJECTIVE: Evaluate the bond strength of a resin cement used to lute carbon fiber
      posts, when drills and 4 different substances were used for the post-space
      preparation. STUDY DESIGN: Forty human canines were treated endodontically, and
      had a 10-mm length post space preparation. Four different substances were used
      with the drills: G1 -saline, G2 -2% chlorhexidine gel, G3 -EDTA/NaOCl, and G4 
      xylene. Carbon fiber posts (C-Post) were cemented with Allbond2 and Hi-X. Then,
      the posts were dislodged by tensional forces. RESULTS: The groups of
      chlrohexidine (G2) and xylene (G4) obtained superior average values of bond
      strength at the 5% significance level (Parametric analyzes ANOVA/Tukey/Scheffe)
      differing statistically from the other groups. There was no statistical
      significant difference between groups 2 and 4. CONCLUSION: Xylene and
      chlorhexidine gel are good substances for the post-space preparation but the
      second has the advantage of antimicrobial activity and low toxicity.

PMID- 15716849
TI  - The risk of furcal perforation in mandibular molars using Gates-Glidden drills
      with anticurvature pressure.
AB  - OBJECTIVE: The aim of this study was to determine whether using Gates-Glidden
      (GG) drills and anticurvature pressure in curved mesial root canals of mandibular
      molars could remove more dentin from the mesial canal wall and remove less dentin
      from the distal canal wall at a level 2 mm below the furcation. STUDY DESIGN: In
      5 groups of mesial roots with an average curvature of 32-34 degrees, 103 canals
      were prepared using a size #2 or #3 GG drill in the coronal third (straight
      portion of the canal only) or coronal half (straight portion and part of the
      curved portion), with or without applying anticurvature pressure. Using a
      modification of the Bramante muffle mold the cross-section of the mesial root at
      2 mm below bifurcation was photographed twice, before and after the use of GG;
      the photos were then scanned as tagged image files. The thickness of the mesial
      and distal canal walls wer measured using an image analysis program. The
      reduction of the wall thickness after the use of GG was calculated. RESULTS:
      Before enlargement, the average and minimal thickness of the distal wall was 0.92
      and 0.43 mm respectively, thinner than that of the mesial wall (1.50 and 0.87 mm,
      correspondingly). After the use of GG, the reduction of the mesial wall was
      similar to the reduction of the distal wall (P > .05 for all groups). In 4 groups
      the maximal reduction of the distal wall was > or =0.72 mm. CONCLUSIONS: After
      using GG drills and anticurvature pressure, dentin was uniformly removed
      regardless of the size of the GG and the depth of placement of GG. Flaring with
      GG drills in mandibular molars may result in perforations; application of
      anticurvature pressure did not reduce the risk.

PMID- 15716850
TI  - Effect of a low-concentration EDTA solution on root canal walls: a scanning
      electron microscopic study.
AB  - OBJECTIVES: The aim of this study was to evaluate, in vitro, the ability of an 8%
      EDTA solution to remove debris and smear produced during root canal preparation.
      STUDY DESIGN: Single-rooted human teeth were used for this experiment. All root
      canals were instrumented in a similar fashion and irrigated with a 3.5% NaOCl
      solution. The teeth were divided into 6 groups. According to the groups, various
      final flushes were performed with a 15% or 8% EDTA solution for 1 or 3 min and
      with or without saline rinsing. After preparation, roots were separated into 3
      thirds and each third was observed by SEM. Debris (D) and root canal smear (S)
      was evaluated twice. RESULTS: The results were subjected to ANOVA. The D and S
      scores for all test groups were statistically different from the control group
      without EDTA flush (P = .0001). The lowest D and S scores were obtained by a 3
      min rinse with 8% EDTA solution and a statistical difference was observed in the
      apical third (P < .05). CONCLUSION: Under these in vitro conditions, 3 min 8%
      EDTA irrigation is as effective as 1 min 15% EDTA irrigation.

PMID- 15716851
TI  - Changes in the arterial fraction of human cerebral blood volume during
      hypercapnia and hypocapnia measured by positron emission tomography.
AB  - Hypercapnia induces cerebral vasodilation and increases cerebral blood volume
      (CBV), and hypocapnia induces cerebral vasoconstriction and decreases CBV.
      Cerebral blood volume measured by positron emission tomography (PET) is the sum
      of three components, that is, arterial, capillary, and venous blood volumes.
      Changes in arterial blood volume (V(a)) and CBV during hypercapnia and hypocapnia
      were investigated in humans using PET with H(2)(15)O and (11)CO. Arterial blood
      volume was determined from H(2)(15)O PET data by means of a two-compartment model
      that takes V(a) into account. Baseline CBV and values during hypercapnia and
      hypocapnia in the cerebral cortex were 0.034+/-0.003, 0.038+/-0.003, and 0.031+/
      0.003 mL/mL (mean+/-s.d.), respectively. Baseline V(a) and values during
      hypercapnia and hypocapnia were 0.015+/-0.003, 0.025+/-0.011, and 0.007+/-0.003
      mL/mL, respectively. Cerebral blood volume changed significantly owing to changes
      in PaCO(2), and V(a) changed significantly in the direction of CBV changes.
      However, no significant change was observed in venous plus capillary blood volume
      (=CBV-V(a)). This indicates that changes in CBV during hypercapnia and hypocapnia
      are caused by changes in arterial blood volume without changes in venous and
      capillary blood volume.

PMID- 15716853
TI  - Regional heterogeneity of 5-HT1A receptors in human cerebellum as assessed by
      positron emission tomography.
AB  - Two measures used in brain imaging are binding potential (BP) and the specific to
      nonspecific equilibrium partition coefficient (V(3)''). V(3)'' determined using
      the 5-HT(1A) ligand [(11)C]WAY-100635 is sensitive to changes in the free and
      nonspecific binding of the ligand in the reference region (V(2)). Healthy female
      volunteers have higher 5-HT(1A) BP but not V(3)'' compared with men, because V(2)
      is higher in women. While there could be several explanations for this
      observation, we hypothesized that women have more 5-HT(1A) receptors in the
      cerebellum. We explore the cerebellum to define a subregion that more accurately
      represents the free and nonspecific binding, potentially allowing the use of
      V(3)''. A quantitative autoradiogram in human brain using [(3)H]WAY-100635
      identified a cerebellar subregion devoid of 5-HT(1A) receptors. In vivo 5-HT(1A)
      receptors were evaluated using [(11)C]WAY-100635 in 12 healthy women and 13
      healthy men. Each subject had a metabolite-corrected arterial input function. The
      autoradiogram demonstrates the lowest concentration of 5-HT(1A) receptors in the
      cerebellar white matter (CW) and highest concentration in the cerebellar vermis
      (CV). The CW volume of distribution (V(T)) is lower than CV. Cerebellar white
      matter is adequately modeled by a one-tissue compartmental model, while a two
      tissue model is necessary to model CV or the total cerebellum (CT). Women have a
      higher CW V(T) compared with men, suggesting a difference in V(2). Use of CW
      improves identifiability and time stability of BP in cortical regions. Cerebellar
      white matter might be a better reference region for use in future 5-HT(1A)
      studies using [(11)C]WAY-100635. With CW as a reference region, V(3)'' cannot be
      used to detect differences in 5-HT(1A) receptors between men and women,
      suggesting the need for arterial input functions to determine BP.

PMID- 15716852
TI  - Metabolic crisis without brain ischemia is common after traumatic brain injury: a
      combined microdialysis and positron emission tomography study.
AB  - Brain trauma is accompanied by regional alterations of brain metabolism,
      reduction in metabolic rates and possible energy crisis. We hypothesize that
      microdialysis markers of energy crisis are present during the critical period of
      intensive care despite the absence of brain ischemia. In all, 19 brain injury
      patients (mean GCS 6) underwent combined positron emission tomography (PET) for
      metabolism of glucose (CMRglu) and oxygen (CMRO(2)) and cerebral microdialysis
      (MD) at a mean time of 36 h after injury. Microdialysis values were compared with
      the regional mean PET values adjacent to the probe. Longitudinal MD data revealed
      a 25% incidence rate of metabolic crisis (elevated lactate/pyruvate ratio (LPR) >
      40) but only a 2.4% incidence rate of ischemia. Positron emission tomography
      imaging revealed a 1% incidence of ischemia across all voxels as measured by
      oxygen extraction fraction (OEF) and cerebral venous oxygen content (CvO(2)). In
      the region of the MD probe, PET imaging revealed ischemia in a single patient
      despite increased LPR in other patients. Lactate/pyruvate ratio correlated
      negatively with CMRO(2) (P < 0.001), but not with OEF or CvO(2). Traumatic brain
      injury leads to a state of persistent metabolic crisis as reflected by abnormal
      cerebral microdialysis LPR that is not related to ischemia.

PMID- 15716854
TI  - Protein kinase C delta cleavage initiates an aberrant signal transduction pathway
      after cardiac arrest and oxygen glucose deprivation.
AB  - Protein kinase C (PKC) isozymes have been known to mediate a variety of complex
      and diverse cellular functions. deltaPKC has been implicated in mediating
      apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and
      oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested
      whether an ischemic insult promoted deltaPKC cleavage during the reperfusion and
      whether the upstream pathway involved release of cytochrome c and caspase 3
      cleavage. We showed that cardiac arrest/OGD significantly enhanced deltaPKC
      translocation and increased its cleavage at 3 h of reperfusion. Since deltaPKC is
      one of the substrates for caspase 3, we next determined caspase 3 activation
      after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was
      observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined
      cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c
      in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition
      of either deltaPKC/caspase 3 during OGD and early reperfusion resulted in
      neuroprotection in CA1 region of hippocampus. Our results support the deleterious
      role of deltaPKC in reperfusion injury. We propose that early cytochrome c
      release and caspase 3 activation promote deltaPKC translocation/cleavage.

PMID- 15716856
TI  - Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury:
      support for a neuroprotective role of iNOS.
AB  - Studies in experimental traumatic brain injury (TBI) suggest both deleterious and
      protective effects of inducible nitric oxide synthase (iNOS). Early after injury,
      iNOS may be detrimental via formation of peroxynitrite and iNOS inhibitors are
      protective. In contrast, we reported impaired long-term functional outcome after
      TBI in iNOS knockout (ko) versus wild-type (wt) mice. To elucidate potential
      neuroprotective and neurotoxic mechanisms for iNOS, we studied nitric oxide
      formation by electron paramagnetic resonance (EPR) spectroscopy using
      diethyldithiocarbamate-iron (DETC-Fe) as a spin trap and markers of nitrosative
      (S-nitrosothiol (RSNO, Fluorescent assay); nitrotyrosine (3NT, ELISA)) and
      oxidative stress (ascorbate, HPLC) at 72 h after controlled cortical impact (CCI)
      in iNOS ko and wt and in uninjured iNOS ko and wt mice. 3NT immunostaining with
      macrophage and myeloperoxidase (MPO) dual labeling was also assessed in brain
      sections. Brain DETC-Fe-NO low-temperature EPR signal intensity was approximately
      2-fold greater in wt versus iNOS ko at 72 h after CCI. Ascorbate levels decreased
      in injured hemisphere in wt and iNOS ko versus uninjured -this decrease was more
      pronounced in iNOS ko. In wt mice, RSNO and 3NT levels were increased after CCI
      versus uninjured (50% and 400%, respectively, P < 0.05). RSNO levels were not
      increased in iNOS ko after CCI. Nitrotyrosine levels increased after CCI in wt
      and ko versus respective uninjured -this increase was more pronounced in wt (2.34
      +/- 0.95 versus 1.27 +/- 0.49 pmol/mg protein, P < 0.05). Increased 3NT
      immunoreactivity was detected in wt versus iNOS ko at 72 h after CCI, and
      colocalized with macrophage marker and MPO. Our data support a role for iNOS
      derived NO as an endogenous antioxidant after CCI. iNOS also contributes protein
      nitrosylation and nitration. Colocalization of 3NT with macrophages and MPO
      suggests generation of nitrating agents by macrophages and/or phagocytosis of
      nitrated proteins.

PMID- 15716855
TI  - Protective effects of statins involving both eNOS and tPA in focal cerebral
      ischemia.
AB  - Previous studies have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors (statins) protect the brain against ischemic injury by
      upregulating endothelial nitric oxide synthase (eNOS). Here, we tested the
      hypothesis that statins provide additional beneficial effects by also
      upregulating endogenous tissue plasminogen activator (tPA) and enhancing clot
      lysis in a mouse model of embolic focal ischemia. Heterologous blood clots (0.2
      mm) were injected into the distal internal carotid artery to occlude blood flow
      in the middle cerebral artery territory after long-term (14 days) simvastatin,
      atorvastatin or vehicle treatment. Ischemic lesion volume, neurologic deficits,
      as well as residual blood clots were measured at 22 h. Reverse transcription
      polymerase chain reaction assessed mRNA levels of eNOS, tPA, and the endogenous
      plasminogen activator inhibitor PAI-1. Ischemic lesion volumes and neurologic
      deficits were significantly reduced in wild-type mice by both simvastatin and
      atorvastatin. Statins increased eNOS and tPA mRNA levels but did not change mRNA
      levels of PAI-1. In eNOS knockout mice, atorvastatin reduced the volume of
      ischemic tissue and improved neurologic outcomes after arterial occlusion by
      blood clot emboli. In contrast, statins did not have protective effects in tPA
      knockout mice after embolic focal ischemia, but only in a filament model where
      focal ischemia was achieved via mechanical occlusion. These results suggest that
      statins protect against stroke by multiple mechanisms involving both eNOS and
      tPA. The involvement of each pathway may be revealed depending on the choice of
      experimental stroke model.

PMID- 15716857
TI  - Neuroprotection against focal ischemic brain injury by inhibition of c-Jun N
      terminal kinase and attenuation of the mitochondrial apoptosis-signaling pathway.
AB  - c-Jun N-terminal kinase (JNK) is an important stress-responsive kinase that is
      activated by various forms of brain insults. In this study, we have examined the
      role of JNK activation in neuronal cell death in a murine model of focal ischemia
      and reperfusion; furthermore, we investigated the mechanism of JNK in apoptosis
      signaling, focusing on the mitochondrial-signaling pathway. We show here that JNK
      activity was induced in the brain 0.5 to 24 h after ischemia. Systemic
      administration of SP600125, a small molecule JNK-specific inhibitor, diminished
      JNK activity after ischemia and dose-dependently reduced infarct volume. c-Jun N
      terminal kinase inhibition also attenuated ischemia-induced expression of Bim,
      Hrk/DP5, and Fas, but not the expression of Bcl-2 or FasL. In strong support of a
      role for JNK in promoting the mitochondrial apoptosis-signaling pathway, JNK
      inhibition prevented ischemia-induced mitochondrial translocation of Bax and Bim,
      release of cytochrome c and Smac, and activation of caspase-9 and caspase-3. The
      potential mechanism by which JNK promoted Bax translocation after ischemia was
      further studied using coimmunoprecipitation, and the results revealed that JNK
      activation caused serine phosphorylation of 14-3-3, a cytoplasmic sequestration
      protein of Bax, leading to Bax disassociation from 14-3-3 and subsequent
      translocation to mitochondria. These results confirm the role of JNK as a
      critical cell death mediator in ischemic brain injury, and suggest that one of
      the mechanisms by which JNK triggers the mitochondrial apoptosis-signaling
      pathway is via promoting Bax and Bim translocation.

PMID- 15716858
TI  - Activation of cytokine signaling through leukemia inhibitory factor receptor
      (LIFR)/gp130 attenuates ischemic brain injury in rats.
AB  - Cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 is
      known to exert a neurotrophic action in the central nervous system, although the
      role of this signaling in cerebral ischemia remains unknown. We examined the
      effect of intracerebral injection of LIF after focal cerebral ischemia in rats.
      The animals underwent a sham operation (sham group) or middle cerebral artery
      occlusion (MCAO) followed by direct injection of either vehicle (phosphate
      buffered saline, the PBS group) or recombinant LIF (10 ng in the low-LIF group
      and 100 ng in the high-LIF group) into the cerebral cortex adjacent to the inner
      boundary zone of the infarct area, and neurologic and histologic evaluations were
      conducted 24 h later. Expression of LIFR, gp130, and phosphorylated Stat3, Akt,
      and ERK1/2 was investigated by Western blot analysis and immunohistochemistry.
      The neurologic deficits and ischemic damage were significantly less severe in the
      high-LIF group than in the PBS group and the low-LIF group. Leukemia inhibitory
      factor receptor and gp130 were expressed in neurons, and the ischemic damage of
      these proteins was rescued in the high-LIF group. Early induction of
      phosphorylated Stat3 was significantly detected on the ischemic side in the high
      LIF group after LIF injection. Exogenous LIF attenuates ischemic brain injury by
      activating cytokine signaling through LIFR/gp130.

PMID- 15716859
TI  - Quantitative evaluation of BBB permeability after embolic stroke in rat using
      MRI.
AB  - We sought to identify magnetic resonance imaging (MRI) parameters that can
      identify as well as predict disruption of the blood-brain barrier (BBB) after
      embolic stroke in the rat. Rats subjected to embolic stroke with (n=13) and
      without (n=13) rt-PA treatment were followed with MRI using quantitative
      permeability-related parameters, consisting of: transfer constant (K(i)) of Gd-
      DTPA, the distribution volume (V(p)) of the mobile protons, and the inverse of
      the apparent forward transfer rate for magnetization transfer (k(inv)), as well
      as the apparent diffusion coefficient of water (ADC(w)), T2, and cerebral
      cerebral blood flow (CBF). Tissue progressing to fibrin leakage resulting from
      BBB disruption and adjacent tissue were then analyzed to identify MRI markers
      that characterize BBB disruption. Animals were killed after final MRI
      measurements at 24 h after induction of embolic stroke and cerebral tissues were
      perfused and stained to detect fibrin leakage. K(i), V(p), and k(inv) were the
      most sensitive early (2 to 3 h) indices of the cerebral tissue that progresses to
      fibrin leakage. Cerebral blood flow was not significantly different between
      ischemic tissue with a compromised and an intact BBB. Our data indicate that
      compromise of the BBB can be sensitively predicted using a select set of MR
      parameters.

PMID- 15716860
TI  - Transient changes in cortical glucose and lactate levels associated with peri
      infarct depolarisations, studied with rapid-sampling microdialysis.
AB  - Peri-infarct depolarisations (PIDs) contribute to infarct expansion in
      experimental focal ischaemia; furthermore, depolarisations propagate in the
      injured human brain. Glucose utilisation is increased under both conditions, and
      depletion of brain glucose carries a poor prognosis. We studied dynamics of
      cerebral glucose and lactate in relation to PID patterns in experimental stroke.
      The middle cerebral artery was occluded for 3 h in 23 cats under terminal
      chloralose anaesthesia. We used fluorescence imaging to detect occurrence of
      PIDs, and rapid-sampling online microdialysis (rsMD), coupled to a flow-injection
      assay, to examine changes in cerebral cortical extracellular glucose and lactate
      at intervals of 30 sec each. After 30 min' ischaemia, lactate had increased by
      43.6+/-s.d. 45.9 micromol/L, and stabilised in that range for 3 h. In contrast,
      glucose fell only slightly initially (11.9+/-9.7 micromol/L), but progressively
      decreased to a reduction of 56.7+/-47.2 micromol/L at 3 h, with no evidence of
      stabilisation. There was a highly significant inverse relationship of frequency
      of PIDs with plasma glucose (P<0.001). The results also characterise a metabolic
      signature for PIDs for possible application in clinical work, and emphasise
      potential risks in the use of insulin to control plasma glucose in patients with
      brain injury.

PMID- 15716863
TI  - Downregulation of major histocompatibility complex antigens in invading glioma
      cells: stealth invasion of the brain.
AB  - Invasion into surrounding brain tissue is a fundamental feature of gliomas and
      the major reason for treatment failure. The process of brain invasion in gliomas
      is not well understood. Differences in gene expression and/or gene products
      between invading and noninvading glioma cells may identify potential targets for
      new therapies. To look for genes associated with glioma invasion, we first
      employed Affymetrix microarray Genechip technology to identify genes
      differentially expressed in migrating glioma cells in vitro and in invading
      glioma cells in vivo using laser capture microdissection. We observed
      upregulation of a variety of genes, previously reported to be linked to glioma
      cell migration and invasion. Remarkably, major histocompatiblity complex (MHC)
      class I and II genes were significantly downregulated in migrating cells in vitro
      and in invading cells in vivo. Decreased MHC expression was confirmed in
      migrating glioma cells in vitro using RT-PCR and in invading glioma cells in vivo
      by immunohistochemical staining of human and murine glioblastomas for beta2
      microglobulin, a marker of MHC class I protein expression. To the best of our
      knowledge, this report is the first to describe the downregulation of MHC class I
      and II antigens in migrating and invading glioma cells, in vitro and in vivo,
      respectively. These results suggest that the very process of tumor invasion is
      associated with decreased expression of MHC antigens allowing glioma cells to
      invade the surrounding brain in a 'stealth'-like manner.

PMID- 15716864
TI  - Sarcoidosis and immunoglobulin lambda II light-chain amyloidosis diagnosed after
      orthotopic heart transplantation: a case report and review of the literature.
AB  - Cardiac involvement by sarcoidosis and concomitant deposition of AL amyloid is an
      uncommon association. We describe the case of a 53-year-old African-American man
      with a 7-year history of dilated nonischemic cardiomyopathy and severe cardiac
      failure who underwent orthotopic heart transplantation. His prior cardiac
      biopsies had only mild myocyte hypertrophy and minimal interstitial fibrosis.
      After surgery, numerous sarcoid granulomas and amyloid deposition were identified
      in the native heart. Six days after the transplant the patient died due to
      aspiration bronchopneumonia and acute renal failure. At autopsy, both sarcoidosis
      and immunoglobulin (Ig) lambda light-chain amyloidosis were present in the native
      atria, lungs, thyroid, liver, spleen, and kidneys. Sarcoid granulomas alone were
      present in the parathyroids, lymph nodes, and bone marrow. Amyloid deposition
      alone was present in the aorta, stomach, large bowel, and urinary bladder. There
      was no evidence of plasma cell dyscrasia, or underlying gammopathy. This unusual
      association was described in only two other cases in the medical literature.
      However, this is the first case of sarcoidosis and AL amyloidosis with successful
      sequencing and identification of Ig lambda light-chain amyloid, and in which
      there was no evidence of plasma cell dyscrasia.

PMID- 15716870
TI  - The President's New Year message.

PMID- 15716871
TI  - Classification approach.

PMID- 15716872
TI  - Life-stages.

PMID- 15716881
TI  - Endodontic treatment for children.
AB  - Root canal treatment for children has particular difficulties and considerations.
      It must be planned in light of the remaining teeth, and the need for balancing or
      compensating extraction borne in mind. Diagnosis may be difficult, as may
      prolonged treatment under local anaesthesia and rubber dam. Vital pulpotomy
      techniques with formocresol and/or calcium hydroxide must be carefully executed
      in line with the UK National Guidelines. The treatment of the avulsed tooth has
      been the subject of much research, and practitioners should ensure that they are
      up-to-date with current treatment modalities.

PMID- 15716882
TI  - Quality of written prescriptions and master impressions for fixed and removable
      prosthodontics: a comparative study.
AB  - AIM: Various ethical and legal guidelines require dental practitioners to
      adequately design, prescribe and fabricate good quality prostheses. The purpose
      of this investigation was to examine the quality of written instructions and
      choice of impression trays and materials for both fixed and removable
      prosthodontics in Ireland and the United Kingdom. MATERIALS AND METHODS: A pre
      piloted questionnaire was distributed to a number of large commercial
      laboratories geographically distributed throughout the United Kingdom and
      Ireland. Information was sought relating to the quality of written instructions
      and use of impression trays and materials for three forms of 'dental precision
      casting' - cobalt-chromium based removable partial dentures, full veneer
      porcelain-fused-to-metal crowns, and conventional fixed bridges. RESULTS: Six
      hundred questionnaires were distributed, and information was received relating to
      447 items of prosthodontic treatment (response rate= 75%). Ninety-five per cent
      of cases were privately funded. Using pre-determined grading criteria, poor or no
      written instructions were provided in one-half of cases examined. One-half of
      master impressions were made using a plastic stock tray. The technician felt that
      material had been appropriately disinfected prior to being sent to the laboratory
      in only 57% of cases. CONCLUSION: The written instructions and master impressions
      examined in this study failed to meet the relevant ethical and legal guidelines
      in approximately 50% of cases.

PMID- 15716890
TI  - Assessing adherence with toothbrushing instructions using a data logger
      toothbrush.
AB  - OBJECTIVES: To evaluate patient compliance with toothbrushing instructions using
      a data logger and a brushing diary. METHODS: Dental patients were provided with
      powered toothbrushes modified to carry electronic data loggers. Demonstration of
      the most effective way to use the toothbrush was provided with instructions to
      brush for 2 minutes morning and evening. Data logger brushes were supplied for
      two episodes of 8 weeks. Brushing time was also recorded in a diary during
      episode 1. RESULTS: Data from 14 brushes (2,287 recordings) were used to evaluate
      compliance in episode 1 Nine brushes (1,526 recordings) were used in episode 2 A
      total of 2,333 brushing events were reported manually in the diaries. Data logger
      records during episode 1 showed that only 34% of events were compliant with the
      instruction of a 2 minute brushing time, 20% were partially compliant (within +/
      30s of 2 minutes), and 46% of events were non-compliant (>30s from 2 minutes).
      The respective proportions for episode 2 were 24%, 24% and 52%. Diary data
      reported 58% of events as compliant with 42% non-compliant. CONCLUSIONS: Manually
      completed brushing diaries do not provide an accurate reflection of subjects'
      compliance with toothbrushing instructions.

PMID- 15716891
TI  - Effectiveness in controlling haemorrhage after dental scaling in people with
      haemophilia by using tranexamic acid mouthwash.
AB  - AIMS: To compare the effectiveness of tranexamic acid mouthwash (TAMW) in
      controlling gingival haemorrhage after dental scaling with that of using factor
      replacement therapy (FRT) prior to dental scaling in people with haemophilia.
      DESIGN: Double-blind cross-over randomised control trial. SETTING: Dedicated
      hospital dental practice for patients with inherited bleeding disorders. METHOD:
      Sixteen patients with haemophilia who required dental scaling participated in
      this pilot study. The experimental treatment regime (ETR) involved transfusing
      each patient with saline before scaling both quadrants on one side of the mouth
      followed by oral rinsing with TAMW four times daily for up to eight days. The
      control regime (CR) involved giving each patient FRT before scaling the opposite
      side of the mouth followed by use of a placebo TAMW. Each patient underwent both
      treatments in a random-ised sequence. Both the operator and the patients were
      unaware of which were the ETR and CR episodes. On both occasions the patient kept
      a log book of the rinsing regime and any post-operative bleeding. Additionally, a
      structured post-treatment telephone interview was conducted to assess the
      effectiveness and the patient acceptability of the ETR. RESULTS: Thirteen
      patients completed the study. No statistically significant difference was found
      in gingival bleeding and mouthwashing frequencies between the ETR and the CR (p >
      0.05). Five patients reported no gingival bleeding with either the ETR or the CR.
      No patient, using either regime, required extra FRT due to gingival haemorrhage.
      All subjects found the ETR acceptable and easy and reported feeling safe in using
      TAMW alone to control gingival bleeding after dental scaling. CONCLUSION: TAMW
      use after dental scaling was as effective as using FRT beforehand in controlling
      gingival haemorrhage for people with haemophilia.

PMID- 15716892
TI  - Contemporary dental practice in the UK: demographic data and practising
      arrangements.
AB  - OBJECTIVES: To investigate, by questionnaire, various aspects of primary dental
      care provision in the North West of England and Scotland. METHOD: A questionnaire
      containing 79 questions was sent to 1,000 practitioners, selected at random, in
      the North West of England and Scotland. Non-responders were sent another
      questionnaire after a period of 4 weeks had elapsed. RESULTS: Overall a response
      rate of 70% was achieved. The majority of practitioners were practice principals
      (65%), working in a group NHS practice (80%) located in a city or town centre
      (49%). On average 10-20 patients were treated each session with fewer patients
      treated per session under private arrangements. Many practitioners were found to
      lack hygienist support (44%) and to employ unqualified dental nurses (82%).
      Younger practitioners were more likely than senior colleagues to have access to
      up-to-date computers whilst 37% and 74% of respondents never used CAL programmes
      or magnification respectively. Contemporary cross-infection control standards
      were used by the majority of practitioners, although 3% of practitioners reported
      only autoclaving their handpiece once a day. CONCLUSIONS: The majority of
      practitioners, involved in this study, worked under National Health Service (NHS)
      regulations as principals in a group practice where the workload was greater than
      the private/independent sector. Contemporary cross-infection procedures were used
      routinely. In contrast computer-aided learning programmes and magnification were
      not used routinely. The practitioners in this study employed significant numbers
      of unqualified dental nurses.

PMID- 15716893
TI  - Development and evaluation of a questionnaire to evaluate clinical dental
      teachers (ECDT).
AB  - OBJECTIVES: To develop and test the psychometric properties (validity and
      reliability) of a questionnaire to evaluate clinical dental teachers. METHODS: An
      item (question) pool was generated with the use of a literature review, feedback
      from faculty staff, and from focus group discussions with dental students.
      Following factor analysis the validity and reliability of a revised questionnaire
      was assessed. This involved 148 dental students and 453 assessments of 29
      clinical dental teachers. RESULTS: Effective clinical dental teaching (ECDT)
      scores were associated with 'global ratings' of the effectiveness of clinical
      dental teaching (P<0.01), indicating strong criterion validity. In comparison
      analysis there was strong agreement between students regarding ratings of
      individual clinical dental teachers, indicating good construct validity.
      Reliability was assessed by examining internal consistency of sub-scales and
      overall ECDT scale, and found to be good (Cronbach alpha's > 0.80). CONCLUSION: A
      valid and reliable measure to evaluate clinical dental teachers has been
      developed for use in a clinical academia setting, and has potential use as a
      quality assurance measure.

PMID- 15716906
TI  - Genome-wide association studies for common diseases and complex traits.
AB  - Genetic factors strongly affect susceptibility to common diseases and also
      influence disease-related quantitative traits. Identifying the relevant genes has
      been difficult, in part because each causal gene only makes a small contribution
      to overall heritability. Genetic association studies offer a potentially powerful
      approach for mapping causal genes with modest effects, but are limited because
      only a small number of genes can be studied at a time. Genome-wide association
      studies will soon become possible, and could open new frontiers in our
      understanding and treatment of disease. However, the execution and analysis of
      such studies will require great care.

PMID- 15716907
TI  - Genome-wide association studies: theoretical and practical concerns.
AB  - To fully understand the allelic variation that underlies common diseases,
      complete genome sequencing for many individuals with and without disease is
      required. This is still not technically feasible. However, recently it has become
      possible to carry out partial surveys of the genome by genotyping large numbers
      of common SNPs in genome-wide association studies. Here, we outline the main
      factors - including models of the allelic architecture of common diseases, sample
      size, map density and sample-collection biases - that need to be taken into
      account in order to optimize the cost efficiency of identifying genuine disease
      susceptibility loci.

PMID- 15716908
TI  - The genetic theory of adaptation: a brief history.
AB  - Theoretical studies of adaptation have exploded over the past decade. This work
      has been inspired by recent, surprising findings in the experimental study of
      adaptation. For example, morphological evolution sometimes involves a modest
      number of genetic changes, with some individual changes having a large effect on
      the phenotype or fitness. Here I survey the history of adaptation theory,
      focusing on the rise and fall of various views over the past century and the
      reasons for the slow development of a mature theory of adaptation. I also discuss
      the challenges that face contemporary theories of adaptation.

PMID- 15716909
TI  - Neonatal screening by DNA microarray: spots and chips.
AB  - Newborn screening (NBS) is a public-health genetic screening programme aimed at
      early detection and treatment of pre-symptomatic children affected by specific
      disorders. It currently involves protein-based assays and PCR to confirm abnormal
      results. We propose that DNA microarray technology might be an improvement over
      protein assays in the first stage of NBS. This approach has important advantages,
      such as multiplex analysis, but also has disadvantages, which include a high
      initial cost and the analysis/storage of large data sets. Determining the optimal
      technology for NBS will require that technical, public health and ethical
      considerations are made for the collection and extent of analysis of paediatric
      genomic data, for privacy and for parental consent.

PMID- 15716910
TI  - Conserved non-genic sequences - an unexpected feature of mammalian genomes.
AB  - Mammalian genomes contain highly conserved sequences that are not functionally
      transcribed. These sequences are single copy and comprise approximately 1-2% of
      the human genome. Evolutionary analysis strongly supports their functional
      conservation, although their potentially diverse, functional attributes remain
      unknown. It is likely that genomic variation in conserved non-genic sequences is
      associated with phenotypic variability and human disorders. So how might their
      function and contribution to human disorders be examined?

PMID- 15716911
TI  - Africa 2005.

PMID- 15716913
TI  - Nuclear-physics research falls foul of budget cuts.

PMID- 15716912
TI  - Salt sellers challenge US health agency using data-quality act.

PMID- 15716914
TI  - US extends security clearance for scholars.

PMID- 15716915
TI  - Europe's research still lacks competitive edge, says panel.

PMID- 15716916
TI  - Online access offers fresh scope for bug identification.

PMID- 15716917
TI  - Sanctions agreed over teenager's gene-therapy death.

PMID- 15716918
TI  - Scientists urged to end feud with White House.

PMID- 15716919
TI  - Global geoscience suffers as UNESCO curtails funding.

PMID- 15716922
TI  - Space technology: setting sail for history.

PMID- 15716920
TI  - India's nuclear debate hots up after tsunami floods reactor.

PMID- 15716924
TI  - Emissions control needs atmospheric verification.

PMID- 15716923
TI  - Cell biology: hopping fences.

PMID- 15716925
TI  - No political will to seek innovative contraception.

PMID- 15716930
TI  - Schrodinger's mousetrap. Part 5.

PMID- 15716931
TI  - Optoelectronics: silicon shines on.

PMID- 15716933
TI  - Surface chemistry: oiled acrobatics.

PMID- 15716932
TI  - Cell biology: divide and conquer.

PMID- 15716934
TI  - Evolutionary biology: the power of natural selection.

PMID- 15716936
TI  - Planetary science: Saturn's mixed magnetosphere.

PMID- 15716937
TI  - Neurodegeneration: cellular defences destroyed.

PMID- 15716938
TI  - Neurobiology: bright blue times.

PMID- 15716939
TI  - Obituary: Ernst Mayr (1904-2005).

PMID- 15716941
TI  - Insect behaviour: migratory bands give crickets protection.
AB  - Mormon crickets and juvenile locusts form huge migratory bands--millions of
      individuals march in unison across the landscape and devastate vast agricultural
      areas, but little is known about why these bands form. Here we use radiotelemetry
      to show that band membership benefits these insects by greatly reducing the
      probability that they will become victims of predators. It is likely that
      migratory banding has evolved because it gives substantial protection to
      individuals within the group.

PMID- 15716942
TI  - Chemical communication: butterfly anti-aphrodisiac lures parasitic wasps.
AB  - To locate their hosts, parasitic wasps can 'eavesdrop' on the intraspecific
      chemical communications of their insect hosts. Here we describe an example in
      which the information exploited by the parasitic wasp Trichogramma brassicae is a
      butterfly anti-aphrodisiac that is passed from male to female Pieris brassicae
      butterflies during mating, to render them less attractive to conspecific males.
      When the tiny wasp detects the odour of a mated female butterfly, it rides on her
      (Fig. 1) to her egg-laying sites and then parasitizes the freshly laid eggs. If
      this fascinating strategy is widespread in nature, it could severely constrain
      the evolution of sexual communication between hosts.

PMID- 15716943
TI  - Shape coexistence and triaxiality in the superheavy nuclei.
AB  - Superheavy nuclei represent the limit of nuclear mass and charge; they inhabit
      the remote corner of the nuclear landscape, whose extent is unknown. The
      discovery of new elements with atomic numbers Z > or = 110 has brought much
      excitement to the atomic and nuclear physics communities. The existence of such
      heavy nuclei hangs on a subtle balance between the attractive nuclear force and
      the disruptive Coulomb repulsion between protons that favours fission. Here we
      model the interplay between these forces using self-consistent energy density
      functional theory; our approach accounts for spontaneous breaking of spherical
      symmetry through the nuclear Jahn-Teller effect. We predict that the long-lived
      superheavy elements can exist in a variety of shapes, including spherical, axial
      and triaxial configurations. In some cases, we anticipate the existence of
      metastable states and shape isomers that can affect decay properties and hence
      nuclear half-lives.

PMID- 15716944
TI  - How sleep affects the developmental learning of bird song.
AB  - Sleep affects learning and development in humans and other animals, but the role
      of sleep in developmental learning has never been examined. Here we show the
      effects of night-sleep on song development in the zebra finch by recording and
      analysing the entire song ontogeny. During periods of rapid learning we observed
      a pronounced deterioration in song structure after night-sleep. The song regained
      structure after intense morning singing. Daily improvement in similarity to the
      tutored song occurred during the late phase of this morning recovery; little
      further improvement occurred thereafter. Furthermore, birds that showed stronger
      post-sleep deterioration during development achieved a better final imitation.
      The effect diminished with age. Our experiments showed that these oscillations
      were not a result of sleep inertia or lack of practice, indicating the possible
      involvement of an active process, perhaps neural song-replay during sleep. We
      suggest that these oscillations correspond to competing demands of plasticity and
      consolidation during learning, creating repeated opportunities to reshape
      previously learned motor skills.

PMID- 15716945
TI  - Morphological differences between Saturn's ultraviolet aurorae and those of Earth
      and Jupiter.
AB  - It has often been stated that Saturn's magnetosphere and aurorae are intermediate
      between those of Earth, where the dominant processes are solar wind driven, and
      those of Jupiter, where processes are driven by a large source of internal
      plasma. But this view is based on information about Saturn that is far inferior
      to what is now available. Here we report ultraviolet images of Saturn, which,
      when combined with simultaneous Cassini measurements of the solar wind and Saturn
      kilometric radio emission, demonstrate that its aurorae differ morphologically
      from those of both Earth and Jupiter. Saturn's auroral emissions vary slowly;
      some features appear in partial corotation whereas others are fixed to the solar
      wind direction; the auroral oval shifts quickly in latitude; and the aurora is
      often not centred on the magnetic pole nor closed on itself. In response to a
      large increase in solar wind dynamic pressure Saturn's aurora brightened
      dramatically, the brightest auroral emissions moved to higher latitudes, and the
      dawn side polar regions were filled with intense emissions. The brightening is
      reminiscent of terrestrial aurorae, but the other two variations are not. Rather
      than being intermediate between the Earth and Jupiter, Saturn's auroral emissions
      behave fundamentally differently from those at the other planets.

PMID- 15716946
TI  - Solar wind dynamic pressure and electric field as the main factors controlling
      Saturn's aurorae.
AB  - The interaction of the solar wind with Earth's magnetosphere gives rise to the
      bright polar aurorae and to geomagnetic storms, but the relation between the
      solar wind and the dynamics of the outer planets' magnetospheres is poorly
      understood. Jupiter's magnetospheric dynamics and aurorae are dominated by
      processes internal to the jovian system, whereas Saturn's magnetosphere has
      generally been considered to have both internal and solar-wind-driven processes.
      This hypothesis, however, is tentative because of limited simultaneous solar wind
      and magnetospheric measurements. Here we report solar wind measurements,
      immediately upstream of Saturn, over a one-month period. When combined with
      simultaneous ultraviolet imaging we find that, unlike Jupiter, Saturn's aurorae
      respond strongly to solar wind conditions. But in contrast to Earth, the main
      controlling factor appears to be solar wind dynamic pressure and electric field,
      with the orientation of the interplanetary magnetic field playing a much more
      limited role. Saturn's magnetosphere is, therefore, strongly driven by the solar
      wind, but the solar wind conditions that drive it differ from those that drive
      the Earth's magnetosphere.

PMID- 15716947
TI  - An Earth-like correspondence between Saturn's auroral features and radio
      emission.
AB  - Saturn is a source of intense kilometre-wavelength radio emissions that are
      believed to be associated with its polar aurorae, and which provide an important
      remote diagnostic of its magnetospheric activity. Previous observations implied
      that the radio emission originated in the polar regions, and indicated a strong
      correlation with solar wind dynamic pressure. The radio source also appeared to
      be fixed near local noon and at the latitude of the ultraviolet aurora. There
      have, however, been no observations relating the radio emissions to detailed
      auroral structures. Here we report measurements of the radio emissions, which,
      along with high-resolution images of Saturn's ultraviolet auroral emissions,
      suggest that although there are differences in the global morphology of the
      aurorae, Saturn's radio emissions exhibit an Earth-like correspondence between
      bright auroral features and the radio emissions. This demonstrates the
      universality of the mechanism that results in emissions near the electron
      cyclotron frequency narrowly beamed at large angles to the magnetic field.

PMID- 15716948
TI  - A continuous-wave Raman silicon laser.
AB  - Achieving optical gain and/or lasing in silicon has been one of the most
      challenging goals in silicon-based photonics because bulk silicon is an indirect
      bandgap semiconductor and therefore has a very low light emission efficiency.
      Recently, stimulated Raman scattering has been used to demonstrate light
      amplification and lasing in silicon. However, because of the nonlinear optical
      loss associated with two-photon absorption (TPA)-induced free carrier absorption
      (FCA), until now lasing has been limited to pulsed operation. Here we demonstrate
      a continuous-wave silicon Raman laser. Specifically, we show that TPA-induced FCA
      in silicon can be significantly reduced by introducing a reverse-biased p-i-n
      diode embedded in a silicon waveguide. The laser cavity is formed by coating the
      facets of the silicon waveguide with multilayer dielectric films. We have
      demonstrated stable single mode laser output with side-mode suppression of over
      55 dB and linewidth of less than 80 MHz. The lasing threshold depends on the p-i
      n reverse bias voltage and the laser wavelength can be tuned by adjusting the
      wavelength of the pump laser. The demonstration of a continuous-wave silicon
      laser represents a significant milestone for silicon-based optoelectronic
      devices.

PMID- 15716949
TI  - Biological control of terrestrial silica cycling and export fluxes to watersheds.
AB  - Silicon has a crucial role in many biogeochemical processes--for example, as a
      nutrient for marine and terrestrial biota, in buffering soil acidification and in
      the regulation of atmospheric carbon dioxide. Traditionally, silica fluxes to
      soil solutions and stream waters are thought to be controlled by the weathering
      and subsequent dissolution of silicate minerals. Rates of mineral dissolution can
      be enhanced by biological processes. But plants also take up considerable
      quantities of silica from soil solution, which is recycled into the soil from
      falling litter in a separate soil-plant silica cycle that can be significant in
      comparison with weathering input and hydrologic output. Here we analyse soil
      water in basaltic soils across the Hawaiian islands to assess the relative
      contributions of weathering and biogenic silica cycling by using the distinct
      signatures of the two processes in germanium/silicon ratios. Our data imply that
      most of the silica released to Hawaiian stream water has passed through the
      biogenic silica pool, whereas direct mineral-water reactions account for a
      smaller fraction of the stream silica flux. We expect that other systems
      exhibiting strong Si depletion of the mineral soils and/or high Si uptake rates
      by biomass will also have strong biological control on silica cycling and export.

PMID- 15716950
TI  - Pressure sensitivity of olivine slip systems and seismic anisotropy of Earth's
      upper mantle.
AB  - The mineral olivine dominates the composition of the Earth's upper mantle and
      hence controls its mechanical behaviour and seismic anisotropy. Experiments at
      high temperature and moderate pressure, and extensive data on naturally deformed
      mantle rocks, have led to the conclusion that olivine at upper-mantle conditions
      deforms essentially by dislocation creep with dominant [100] slip. The resulting
      crystal preferred orientation has been used extensively to explain the strong
      seismic anisotropy observed down to 250 km depth. The rapid decrease of
      anisotropy below this depth has been interpreted as marking the transition from
      dislocation to diffusion creep in the upper mantle. But new high-pressure
      experiments suggest that dislocation creep also dominates in the lower part of
      the upper mantle, but with a different slip direction. Here we show that this
      high-pressure dislocation creep produces crystal preferred orientations resulting
      in extremely low seismic anisotropy, consistent with seismological observations
      below 250 km depth. These results raise new questions about the mechanical state
      of the lower part of the upper mantle and its coupling with layers both above and
      below.

PMID- 15716951
TI  - Stratigraphic placement and age of modern humans from Kibish, Ethiopia.
AB  - In 1967 the Kibish Formation in southern Ethiopia yielded hominid cranial remains
      identified as early anatomically modern humans, assigned to Homo sapiens.
      However, the provenance and age of the fossils have been much debated. Here we
      confirm that the Omo I and Omo II hominid fossils are from similar stratigraphic
      levels in Member I of the Kibish Formation, despite the view that Omo I is more
      modern in appearance than Omo II. 40Ar/39Ar ages on feldspar crystals from pumice
      clasts within a tuff in Member I below the hominid levels place an older limit of
      198 +/- 14 kyr (weighted mean age 196 +/- 2 kyr) on the hominids. A younger age
      limit of 104 +/- 7 kyr is provided by feldspars from pumice clasts in a Member
      III tuff. Geological evidence indicates rapid deposition of each member of the
      Kibish Formation. Isotopic ages on the Kibish Formation correspond to ages of
      Mediterranean sapropels, which reflect increased flow of the Nile River, and
      necessarily increased flow of the Omo River. Thus the 40Ar/39Ar age measurements,
      together with the sapropel correlations, indicate that the hominid fossils have
      an age close to the older limit. Our preferred estimate of the age of the Kibish
      hominids is 195 +/- 5 kyr, making them the earliest well-dated anatomically
      modern humans yet described.

PMID- 15716952
TI  - Parasites and climate synchronize red grouse populations.
AB  - There is circumstantial evidence that correlated climatic conditions can drive
      animal populations into synchronous fluctuations in abundance. However, it is
      unclear whether climate directly affects the survival and fecundity of
      individuals, or indirectly, by influencing food and natural enemies. Here we
      propose that climate affects trophic interactions and could be an important
      mechanism for synchronizing spatially distributed populations. We show that in
      specific years the size of red grouse populations in northern England either
      increases or decreases in synchrony. In these years, widespread and correlated
      climatic conditions during May and July affect populations regionally and
      influence the density-dependent transmission of the gastrointestinal nematode
      Trichostrongylus tenuis, a parasite that reduces grouse fecundity. This in turn
      forces grouse populations into synchrony. We conclude that specific climatic
      events may lead to outbreaks of infectious diseases or pests that may cause
      dramatic, synchronized changes in the abundance of their hosts.

PMID- 15716953
TI  - Melanopsin-expressing ganglion cells in primate retina signal colour and
      irradiance and project to the LGN.
AB  - Human vision starts with the activation of rod photoreceptors in dim light and
      short (S)-, medium (M)-, and long (L)- wavelength-sensitive cone photoreceptors
      in daylight. Recently a parallel, non-rod, non-cone photoreceptive pathway,
      arising from a population of retinal ganglion cells, was discovered in nocturnal
      rodents. These ganglion cells express the putative photopigment melanopsin and by
      signalling gross changes in light intensity serve the subconscious, 'non-image
      forming' functions of circadian photoentrainment and pupil constriction. Here we
      show an anatomically distinct population of 'giant', melanopsin-expressing
      ganglion cells in the primate retina that, in addition to being intrinsically
      photosensitive, are strongly activated by rods and cones, and display a rare, S
      Off, (L + M)-On type of colour-opponent receptive field. The intrinsic, rod and
      (L + M) cone-derived light responses combine in these giant cells to signal
      irradiance over the full dynamic range of human vision. In accordance with cone
      based colour opponency, the giant cells project to the lateral geniculate
      nucleus, the thalamic relay to primary visual cortex. Thus, in the diurnal
      trichromatic primate, 'non-image-forming' and conventional 'image-forming'
      retinal pathways are merged, and the melanopsin-based signal might contribute to
      conscious visual perception.

PMID- 15716954
TI  - DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C.
      elegans.
AB  - Genetic analyses in Caenorhabditis elegans have been instrumental in the
      elucidation of the central cell-death machinery, which is conserved from C.
      elegans to mammals. One possible difference that has emerged is the role of
      mitochondria. By releasing cytochrome c, mitochondria are involved in the
      activation of caspases in mammals. However, there has previously been no evidence
      that mitochondria are involved in caspase activation in C. elegans. Here we show
      that mitochondria fragment in cells that normally undergo programmed cell death
      during C. elegans development. Mitochondrial fragmentation is induced by the BH3
      only protein EGL-1 and can be blocked by mutations in the bcl-2-like gene ced-9,
      indicating that members of the Bcl-2 family might function in the regulation of
      mitochondrial fragmentation in apoptotic cells. Mitochondrial fragmentation is
      independent of CED-4/Apaf-1 and CED-3/caspase, indicating that it occurs before
      or simultaneously with their activation. Furthermore, DRP-1/dynamin-related
      protein, a key component of the mitochondrial fission machinery, is required and
      sufficient to induce mitochondrial fragmentation and programmed cell death during
      C. elegans development. These results assign an important role to mitochondria in
      the cell-death pathway in C. elegans.

PMID- 15716955
TI  - Rejuvenation of aged progenitor cells by exposure to a young systemic
      environment.
AB  - The decline of tissue regenerative potential is a hallmark of ageing and may be
      due to age-related changes in tissue-specific stem cells. A decline in skeletal
      muscle stem cell (satellite cell) activity due to a loss of Notch signalling
      results in impaired regeneration of aged muscle. The decline in hepatic
      progenitor cell proliferation owing to the formation of a complex involving cEBP
      alpha and the chromatin remodelling factor brahma (Brm) inhibits the regenerative
      capacity of aged liver. To examine the influence of systemic factors on aged
      progenitor cells from these tissues, we established parabiotic pairings (that is,
      a shared circulatory system) between young and old mice (heterochronic
      parabioses), exposing old mice to factors present in young serum. Notably,
      heterochronic parabiosis restored the activation of Notch signalling as well as
      the proliferation and regenerative capacity of aged satellite cells. The exposure
      of satellite cells from old mice to young serum enhanced the expression of the
      Notch ligand (Delta), increased Notch activation, and enhanced proliferation in
      vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte
      proliferation and restored the cEBP-alpha complex to levels seen in young
      animals. These results suggest that the age-related decline of progenitor cell
      activity can be modulated by systemic factors that change with age.

PMID- 15716956
TI  - Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle
      progression.
AB  - The controls that enable melanoblasts and melanoma cells to proliferate are
      likely to be related, but so far no key regulator of cell cycle progression
      specific to the melanocyte lineage has been identified. The microphthalmia
      associated transcription factor Mitf has a crucial but poorly defined role in
      melanoblast and melanocyte survival and in differentiation. Here we show that
      Mitf can act as a novel anti-proliferative transcription factor able to induce a
      G1 cell-cycle arrest that is dependent on Mitf-mediated activation of the
      p21(Cip1) (CDKN1A) cyclin-dependent kinase inhibitor gene. Moreover, cooperation
      between Mitf and the retinoblastoma protein Rb1 potentiates the ability of Mitf
      to activate transcription. The results indicate that Mitf-mediated activation of
      p21Cip1 expression and consequent hypophosphorylation of Rb1 will contribute to
      cell cycle exit and activation of the differentiation programme. The mutation of
      genes associated with melanoma, such as INK4a or BRAF that would affect either
      Mitf cooperation with Rb1 or Mitf stability respectively, would impair Mitf
      mediated cell cycle control.

PMID- 15716957
TI  - Highly coupled ATP synthesis by F1-ATPase single molecules.
AB  - F1-ATPase is the smallest known rotary motor, and it rotates in an anticlockwise
      direction as it hydrolyses ATP. Single-molecule experiments point towards three
      catalytic events per turn, in agreement with the molecular structure of the
      complex. The physiological function of F1 is ATP synthesis. In the ubiquitous
      F0F1 complex, this energetically uphill reaction is driven by F0, the partner
      motor of F1, which forces the backward (clockwise) rotation of F1, leading to ATP
      synthesis. Here, we have devised an experiment combining single-molecule
      manipulation and microfabrication techniques to measure the yield of this
      mechanochemical transformation. Single F1 molecules were enclosed in femtolitre
      sized hermetic chambers and rotated in a clockwise direction using magnetic
      tweezers. When the magnetic field was switched off, the F1 molecule underwent
      anticlockwise rotation at a speed proportional to the amount of synthesized ATP.
      At 10 Hz, the mechanochemical coupling efficiency was low for the
      alpha3beta3gamma subcomplex (F1-epsilon)), but reached up to 77% after
      reconstitution with the epsilon-subunit (F1+epsilon)). We provide here direct
      evidence that F1 is designed to tightly couple its catalytic reactions with the
      mechanical rotation. Our results suggest that the epsilon-subunit has an
      essential function during ATP synthesis.

PMID- 15716959
TI  - Cultivating black gold.

PMID- 15716960
TI  - Baby blues.

PMID- 15716962
TI  - Scientists and societies. Japan Society for the Promotion of Science.

PMID- 15716965
TI  - Brave new allergic world.

PMID- 15716966
TI  - Air pollution and allergy: you are what you breathe.

PMID- 15716967
TI  - Dendritic cells giveth and taketh away.

PMID- 15716968
TI  - The last flag unfurled? A new immunoglobulin isotype in fish expressed in early
      development.

PMID- 15716969
TI  - New look at an old costimulator.

PMID- 15716970
TI  - CTL responses to HIV and SIV: wrestling with smoke.

PMID- 15716971
TI  - Defining 'stemness': Notch and Wnt join forces?

PMID- 15716973
TI  - How T cells 'see' antigen.
AB  - T lymphocytes bearing alphabeta T cell receptors are pivotal in the immune
      response of most vertebrates. For example, helper T cells orchestrate antibody
      production by B cells as well as stimulating other cells, whereas cytotoxic T
      cells kill virally infected or abnormal cells. Regulatory T cells act to dampen
      responsiveness, and natural killer-like T cells monitor lipid metabolism. The
      specificity of these cells is governed by the alphabeta T cell receptors -
      antibody-like heterodimeric receptors that detect antigenic fragments (peptides)
      or lipids bound to histocompatibility molecules. Intriguing clues as to how these
      peculiar ligands are recognized have gradually emerged over the years and tell a
      remarkable story of biochemical and cellular novelty. Here we summarize some of
      the more recent work on alphabeta T cell receptor recognition and discuss the
      implications for activation.

PMID- 15716976
TI  - Identification of epistasis through a partial advanced intercross reveals three
      arthritis loci within the Cia5 QTL in mice.
AB  - Identification of genes controlling complex diseases has proven to be difficult;
      however, animal models may pave the way to determine how low penetrant genes
      interact to promote disease development. We have dissected the Cia5/Eae3
      susceptibility locus on mouse chromosome 3 previously identified to control
      disease in experimental models of multiple sclerosis and rheumatoid arthritis.
      Congenic strains showed significant but small effects on severity of both
      diseases. To improve the penetrance, we have now used a new strategy that defines
      the genetic interactions. The QTL interacted with another locus on chromosome 15
      and a partial advanced intercross breeding of the two congenic strains for eight
      generations accumulated enough statistical power to identify interactions with
      several loci on chromosome 15. Thereby, three separate loci within the original
      QTL could be identified; Cia5 affected the onset of arthritis by an additive
      interaction with Cia31 on chromosome 15, whereas the Cia21 and Cia22 affected
      severity during the chronic phase of the disease through an epistatic interaction
      with Cia32 on chromosome 15. The definition of genetic interactions was a
      prerequisite to dissect the Cia5 QTL and we suggest the partial advanced
      intercross strategy to be helpful also for dissecting other QTL controlling
      complex phenotypes.

PMID- 15716977
TI  - Library-based selection of retroviruses selectively spreading through matrix
      metalloprotease-positive cells.
AB  - Viruses conditionally replicating in cancer cells form an attractive novel class
      of antitumoral agents. To engineer such viruses infectivity can be coupled with
      proteolytic activity of the target cell by modifying the envelope (Env) protein
      of murine leukaemia virus (MLV) with blocking domains that prevent cell entry
      unless they are cleaved off by tumour-associated proteases like the matrix
      metalloproteases (MMP). Here we show that MLV variants selectively spreading
      through MMP-positive cells can be evolved from virus libraries, in which a
      standard MMP-2 substrate peptide connecting the blocking domain CD40L with the
      Env protein was diversified. Passaging the virus library on human fibrosarcoma or
      glioma cell lines resulted in the selection of about 10 virus clones, of which
      the three most frequent ones were shown to become activated by MMPs and to be
      replication competent on MMP-positive cells only. On these cells, the selected
      linker peptides improved the spreading by several orders of magnitude in vitro,
      as well as in tumour xenografts in vivo, approaching the kinetic of the
      unmodified wild-type virus. The data suggest that retroviral protease substrate
      libraries form a potent tool for the engineering of viruses conditionally
      replicating in a given cancer cell type of interest.

PMID- 15716978
TI  - Targeted rearrangement of a chromosomal repeat sequence by transfection of a
      homologous DNA sequence using purified integrase.
AB  - Using a liposomal transfection with purified bovine leukemia virus (BLV)
      integrase, we observed an efficient DNA rearrangement of a chromosomal repeat
      sequence and targeted integration of a part of the transfected plasmid. The BLV
      integrase recognition sequence (IRS) including the 3' end of the BLV LTR U5, one
      of the sites cleaved by the integrase, was essential for the DNA rearrangement,
      and a sequence homologous to the chromosomal DNA neighboring the repeat target
      site had to be placed downstream of the IRS on the transfected plasmid. The
      pSV2neo DNA, including the pBR322 sequence preintegrated into L929 cells (primary
      transfectants), was rearranged by a secondary transfection of a pBR322-based
      hygromycin-resistance plasmid carrying the IRS. We present a model to explain the
      chromosomal DNA rearrangement of the primary clones through a homologous
      recombination-like reaction and amplification of the neighboring sequences.

PMID- 15716979
TI  - The metabolic syndrome: a cause of sexual dysfunction in women.
AB  - Female sexual dysfunction (FSD) is a significant public health problem. We
      assessed the prevalence of FSD in premenopausal women with the metabolic syndrome
      as compared to the general female population. Compared with the control group (N
      = 80), women with the metabolic syndrome (N = 120) had reduced mean full Female
      Sexual Function Index (FSFI) score (23.2+/-5.4 vs 30.1+/-4.7, P < 0.001), reduced
      satisfaction rate (3.5+/-1.1 vs 4.7+/-1.2, P < 0.01), and higher circulating
      levels of C-reactive protein (CRP: 2.2 (0.6/4.9) vs 0.8 (0.2/2.9) mg/l, median
      (interquartile range), P = 0.01). There was an inverse relation between CRP
      levels and FSFI score (r = -0.32, P=0.02). Investigation of female sexuality is
      suggested for patients with the metabolic syndrome.

PMID- 15716980
TI  - Factors influencing sexual function in patients with rectal cancer.
AB  - Only few studies have investigated the impact of surgery for rectal cancer on
      sexual function. Little of that research included quality of life (QoL) aspects
      and hardly any study analyzed the impact of age, gender and type of surgery on
      sexual function. The aim of the presented study was to address these issues. Over
      a 5 y period, EORTC-QLQ-C-30 and a tumor-specific module were prospectively
      administered to patients before surgery, at discharge, 3, 6, 12 and 24 months
      postoperatively. Comparisons were made between patients receiving
      abdominoperineal resection (APR), anterior resection (AR) with or without Pouch
      and Sigmoid resection. Furthermore, effects of surgery on female and male
      patients, and age groups were analyzed. A total of 819 patients participated in
      the study: 412 were males and 407 were females. The groups were comparable in
      terms of adjuvant treatment, tumor stage and histology. Patients after APR and AR
      with Pouch had worst sexual function. Men reported significantly more
      difficulties with sexual enjoyment; furthermore, over time, sexual problems
      created high levels of strain in men that were worse than baseline levels in the
      early postoperative period. These problems tended to remain. Patients aged 69 y
      and younger scored higher for problems with loss of sexual function and sexuality
      related strain than patients aged 70 y and older. The findings in this study
      confirm that QoL changes postsurgery and that factors like type of surgery,
      gender and age have tremendous impact on sexual function and sexual enjoyment.
      APR and AR with Pouch affect sexual function more than AR and resection of the
      lower sigmoid. Through impaired sexual enjoyment, men are put more under strain
      than women. Patients aged 69 y and younger experience more stress through
      deteriorated sexual function.

PMID- 15716981
TI  - The long-term outcome of patients with hypertensive cardiomyopathy.
AB  - The prognosis of dilated cardiomyopathy due to hypertension (HT-DCM) is
      surprisingly unknown, particularly in the absence of coronary disease and
      diabetes. We aimed at investigating the long-term outcome and the predictors of
      mortality in patients with left ventricular systolic dysfunction exclusively due
      to hypertension. From October 1995 to May 2001, 90 consecutive patients with
      echocardiographic fractional shortening (FS) < 30% and 29 control patients with
      FS > or = 30% were included. Obstructive coronary disease was excluded by
      dipyridamole myocardial perfusion imaging in all patients and coronary
      angiography in 60. After a mean follow-up of 4.3+/-1.6 years, the total mortality
      rate of HT-DCM was twice as much higher than that of patients without left
      ventricular systolic dysfunction (P = 0.01). In HT-DCM, the 5-year mortality rate
      was 26%. Univariate analyses selected age and creatinine for being positively
      related to mortality, and body mass index, FS and blood pressure during follow-up
      for being negatively related to mortality. Neither the improvement of left
      ventricular FS nor the decrease in left ventricular mass index was related to
      survival. Multivariate analysis identified (hazard ratio; 95% confidence
      interval) age (1.08; 1.02-1.13), body mass index (0.86; 0.75-0.98), and baseline
      FS (0.88; 0.78-0.98) as independent predictors of mortality. In conclusion, poor
      survival in HT-DCM can be anticipated by the severity of left ventricular
      systolic dysfunction and advanced age. Instead of ominous signs, high blood
      pressure and body mass may predict a more favourable prognosis.

PMID- 15716982
TI  - Association of essential hypertension with a microsatellite marker on chromosome
      17.
AB  - Hypertension is related to sodium intake, and many patients with essential
      hypertension are overweight and have the metabolic syndrome. We therefore studied
      microsatellite markers close to the thiazide-sensitive Na-Cl cotransporter on
      chromosome 16 and a quantitative trait locus for abdominal obesity-metabolic
      syndrome (AOMS2) on chromosome 17, which have been found to be linked to
      hypertension in a previous genome scan in Chinese. There were 84 hypertensive
      subjects (44 men, 40 women, age 53+/-13 years) and 88 normotensive controls (40
      men, 48 women, age 54+/-13 years) recruited. Specific oligonucleotide primers
      were used to amplify genomic DNA spanning the microsatellite markers D16S3396 and
      D17S1303 that consist of ATA and GATA repeats, respectively. We did not find any
      association between D16S3396 and blood pressure. In contrast, the distribution of
      D17S1303 genotypes differed between hypertensive subjects and normal controls (P
      = 0.014). The number of GATA repeats correlated inversely with diastolic blood
      pressure (r = -0.18, P = 0.02) and body mass index (r = -0.12, P = 0.01). Nine
      GATA repeats in D17S1303 were associated with hypertension (OR 2.19, 95% CI 1.08
      4.44, P = 0.027), while 14 GATA repeats were associated with normotension (OR
      0.26, 95% CI 0.10-0.66, P = 0.002). The diastolic blood pressure in those with or
      without the (GATA)9 allele was 85.9+/-13.6 and 79.2+/-13.6 mmHg respectively (P =
      0.01), and in those with or without the (GATA)14 allele it was 73.8+/-11.0 and
      81.8+/-14.0 mmHg respectively (P = 0.003). Our results provide further evidence
      that a gene predisposing to hypertension in Chinese is in the vicinity of the
      microsatellite D17S1303.

PMID- 15716983
TI  - A free-ranging roundtable discussion on hypertension.

PMID- 15716984
TI  - Infection control practices reduce nosocomial infections and mortality in preterm
      infants in Bangladesh.
AB  - OBJECTIVE: The skin is a potential source for invasive infections in neonates
      from developing countries such as Bangladesh, where the level of environmental
      contamination is exceedingly high. A randomized controlled trial was conducted
      from 1998 to 2003 in the Special Care Nursery of a tertiary hospital in
      Bangladesh to test the effectiveness of topical emollient therapy in enhancing
      the skin barrier of preterm neonates less than 33 weeks of gestational age. In
      the initial months of the study, the infection and mortality rates were noted to
      be unacceptably high. Therefore, an infection control program was introduced
      early in the trial to reduce the rate of nosocomial infections. STUDY DESIGN:
      After a comprehensive review of neonatal care practices and equipment to identify
      sources of nosocomial infections, a simple but comprehensive infection control
      program was introduced that emphasized education of staff and caregivers about
      measures to decrease risk of contamination, particularly hand-washing, proper
      disposal of infectious waste, and strict asepsis during procedures, as well as
      prudent use of antibiotics. RESULTS: Infection control efforts resulted in
      declines in episodes of suspected sepsis (47%), cases of culture-proven (61%)
      sepsis, patients with a clinical diagnosis of sepsis (79%), and deaths with
      clinical (82%) or culture-proven sepsis (50%). CONCLUSION: The infection control
      program was shown to be a simple, low-cost, low-technology intervention to reduce
      substantially the incidence of septicemia and mortality in the nursery.

PMID- 15716985
TI  - A randomized, triple-blind, placebo-controlled trial of prophylactic oral
      phenobarbital to reduce the need for phototherapy in G6PD-deficient neonates.
AB  - OBJECTIVE: Decreased conjugation is probably more important than hemolysis for
      causing jaundice in G6PD-deficient neonates. The role of enzyme inducers, like
      phenobarbital, in G6PD deficiency is unclear. This randomized controlled trial
      was performed to evaluate Phenobarbital's role in reducing the need for
      phototherapy among G6PD-deficient neonates. STUDY DESIGN: This stratified,
      randomized, triple-blinded, placebo-controlled trial was conducted in a level III
      NICU. Consecutive babies with gestation >/=34 weeks and birth weight >/=1800 g
      were screened from cord blood. G6PD-deficient neonates, who were otherwise
      healthy, were enrolled. Rh isoimmunization, maternal Phenobarbital use and lack
      of parental consent were exclusion criteria. Subjects were randomly allocated to
      receive 5 mg/kg day of oral phenobarbital/ placebo for first 3 days. They were
      monitored daily for total serum bilirubin (TSB) until declining TSB was
      documented twice. The primary outcome was requirement for phototherapy and
      secondary outcomes were duration of phototherapy, need for exchange transfusion,
      peak TSB and adverse effects. Sample size of 56 could detect a decline in
      phototherapy requirement from 40 to 5% with 80% power and 5% error. RESULTS: Of
      2370 babies screened, 63 were G6PD-deficient. Of them, 56 eligible babies were
      allocated to phenobarbital (n=27) or placebo (n=29). The mean age of
      administration of the first dose was 18.55+/-7.3 h. In total, 44% in
      phenobarbital group and 41% in placebo group required phototherapy (p=1.0). There
      was no significant difference in exchange transfusion rates (18.5 vs 10%,
      p=0.46). No baby had adverse reactions. CONCLUSION: Prophylactic oral
      phenobarbital does not decrease the need for phototherapy or exchange
      transfusions in G6PD-deficient neonates.

PMID- 15716986
TI  - SNAP-II predicts mortality among infants with congenital diaphragmatic hernia.
AB  - OBJECTIVE: Outcomes analysis in congenital diaphragmatic hernia (CDH) requires a
      validated risk-adjustment tool. The purpose of this study was to use the Canadian
      Neonatal Network (CNN) database to validate the Score for Neonatal Acute
      Physiology, Version II (SNAP-II) for prediction of mortality among CDH infants
      admitted to a neonatal intensive care unit (NICU), and to compare this to the
      predictive equation recently developed by the Congenital Diaphragmatic Hernia
      Study Group (CDHSG). STUDY DESIGN: Infants with CDH in the CNN database were
      identified. Bivariate and multivariable logistic regression models were used to
      identify risk factors predictive of mortality. Model predictive performance and
      calibration were assessed using the area under the receiver operator
      characteristic curve and the technique of Hosmer-Lemeshow, respectively, and
      compared with the CDHSG predictive equation. RESULTS: There were 88 patients with
      CDH among 19,507 admissions to CNN hospitals. The mortality rate among CDH
      patients surviving to NICU admission was 17%, and 12.5% received extracorporeal
      membrane oxygenation therapy. Gestational age and admission SNAP-II score
      predicted mortality. Model predictive performance and calibration were optimized
      with these variables combined. The CDHSG equation was equally predictive of
      mortality, but was only marginally calibrated. CONCLUSIONS: SNAP-II is highly
      predictive of mortality among patients with CDH, and can be used to risk-adjust
      these patients.

PMID- 15716987
TI  - Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and
      treatment outcome in children with B-progenitor-cell acute lymphoblastic
      leukemia: a Pediatric Oncology Group study.
AB  - We reported that children with B-progenitor-cell acute lymphoblastic leukemia
      (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of
      methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an
      improved 5-year event-free survival (EFS) (65% (standard error (s.e.) 12%) vs 22%
      (s.e. 9%)). We repeated this study in children with BpALL treated in the early
      1990s. The major change in treatment was the addition of 12 24-h infusions of 1
      g/M2 MTX with leucovorin rescue (IDMTX). In 87 children treated on Pediatric
      Oncology Group (POG) study 9005 and POG 9006, the 5-year EFS for those whose
      lymphoblasts accumulated high levels of MTX and MTXPGs (79.2%, s.e. 8.3%) was not
      significantly different from that of patients with lesser accumulation of MTX and
      MTXPGs (77.7%, s.e. 5.4%). These findings support the notion that higher dose MTX
      therapy has contributed to increased cure, particularly for patients whose
      lymphoblasts accumulate the drug less well.

PMID- 15716988
TI  - Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in
      high-grade B-cell lymphomas.
AB  - B-cell leukaemia or lymphoma with a combination of t(8;14)(q24;q32) of Burkitt
      leukaemia/lymphoma and t(14;18)(q32;q21) of follicular lymphoma may present
      clinically as de novo acute lymphoblastic leukaemia or transformation of
      follicular lymphoma to aggressive histology diffuse lymphoma. A number of cell
      lines have been reported with a complex t(8;14;18) with fusion of MYC, IGH and
      BCL2 on the same derivative 8 chromosome. The objective of this study was to
      determine the frequency and chromosomal features of this der(8)t(8;14;18) in a
      series of acute leukaemias and malignant lymphomas. A database of 1350 leukaemia
      and lymphoma karyotypes was searched for cases with structural alterations
      affecting both 8q24 and 18q21. A total of 55 cases were identified, of which
      eight revealed a complex der(8)t(8;14;18) with an MYC-IGH-BCL2 rearrangement
      resulting from translocation of BCL2 and MYC with a single disrupted IGH allele.
      Molecular cytogenetic investigation is essential to identify cases of high-grade
      leukaemia/lymphoma with concurrent translocations affecting the BCL2 and MYC
      loci.

PMID- 15716990
TI  - Derivative chromosome 9 deletions are a significant feature of childhood
      Philadelphia chromosome positive acute lymphoblastic leukaemia.
AB  - Deletions from the derivative chromosome 9, der(9), of the translocation,
      t(9;22)(q34;q11), at the site of the ABL/BCR fusion gene, have been demonstrated
      by fluorescence in situ hybridisation (FISH), in both Philadelphia chromosome
      (Ph)-positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia
      (ALL). In CML they occur in 10-15% of cases and appear to indicate a worse
      prognosis, whereas in ALL, the situation is unclear. This study presents the
      findings of dual fusion FISH used to detect such deletions in a series of 27 BCR/
      ABL-positive childhood ALL patients. Metaphase FISH was essential for the
      accurate interpretation of interphase FISH signal patterns. Three cases (11%) had
      a single fusion signal, resulting from deletions of the der(9). Three other
      patients with variant translocations and one with an insertion, also had a single
      fusion, but with no evidence of deletions. Gain of a fusion in approximately one
      third of patients indicated a second Ph, which appears to be a diagnostic marker
      of Ph-positive ALL. This study shows that the incidence of deletions from the
      der(9) in childhood ALL is at least as high as that reported for CML.

PMID- 15716989
TI  - Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC)
      following two tightly spaced high-dose chemotherapy courses with G-CSF.
AB  - The purpose of the study was to compare telomere length (TL) in peripheral blood
      progenitor cells (PBPC) collected after two tightly spaced high-dose (hd)
      chemotherapy courses. We assessed 37 previously untreated lymphoma patients
      undergoing a hd-chemotherapy program with autografting. They sequentially
      received hd-cyclophosphamide (CY) and hd-Ara-C, both followed by PBPC harvesting.
      Both post-CY and post-Ara-C harvests were assessed for TL by Southern blot
      analysis. In 12 patients, the assay was also performed on purified CD34+ cells.
      All patients displayed high PBPC mobilization following both hd-CY and hd-Ara-C.
      In all but one patient, TL was shorter in PBPC collected after Ara-C compared to
      CY: 7226bp (range: 4135-9852) vs 8282 bp (range 4895-14860) (P < 0.0001). This
      result was confirmed on CD34+ cells. Platelet recovery in patients receiving post
      Ara-C PBPC was significantly slower compared to those receiving post-CY PBPC. In
      conclusion, (i) administration of tightly spaced hd-chemotherapy courses induces
      marked telomere shortening on harvested PBPC; (ii) engraftment kinetics seem
      slower, with delayed platelet recovery, in patients autografted with PBPC
      suffering marked TL erosion; (iii) long-term follow-up is required to verify
      whether PBPC with shortened telomeres display defective engraftment stability
      and/or risk of secondary leukemia; (iv) TL evaluation is advisable whenever new
      mobilization procedures are developed.

PMID- 15716991
TI  - Gemcitabine and cisplatin in the treatment of advanced non-small cell lung
      cancer: National Cancer Institute Cairo experience.
AB  - AIM OF THE WORK: The aim of the present study is to document the antitumor
      activity of the combination of gemcitabine and cisplatin for the treatment of
      advanced NSCLC, asses the nature and severity of the side effects and elicit the
      impact of the combination chemotherapy on progression free survival and overall
      survival. PATIENTS AND METHODS: From August 1997 to August 2001, we conducted a
      phase II study of gemcitabine and cisplatin in 60 chemonaive patients (21 stage
      IIIB and 39 stage IV). For the first 34 cases, gemcitabine was given at a dose of
      1,000 mg/m2 IV on days 1, 8 and 15 with cisplatin 100 mg/m2 on day 15, every 28
      days. In the following 26 patients, the regimen was modified to gemcitabine 1,250
      mg/m2 days 1 and 8 and cisplatin 80 mg/m2 day 1, every 21 days. RESULTS: Patients
      included 53 males and 7 females [median age, 52 years (range, 28-69)]. Twenty
      nine had adenocarcinoma, 18 large-cell carcinoma and 13 squamous-cell carcinoma.
      Thirty-one patients had a performance status (PS) of 2 and 22 presented with
      weight loss. All patients were evaluable for response. Three patients achieved a
      complete response (CR) and 22 had partial response (PR), giving an overall
      response of 41.7%, with a median duration of 10 months (range, 4-46 months). The
      time to progression (TTP) was 8 months (range, 2-46 months), with a median
      overall survival of 9 months (range, 2-46 months). The one-year survival rate was
      30.3% for the entire study population, 44% for responders, and statistically
      improved in patients with a PS of I and those with no weight loss. A total of 255
      cycles were administered (median, four cycles/patient). Myelosuppression was
      significant (but manageable) with grade 3/4 neutropenia in 32.6% of cases, anemia
      in 18.6% and thrombocytopenia in 20.4%. Nonhematologic toxicity was limited to
      grade 3/4 nausea and vomiting in 28.8% of cases and impaired liver enzymes in
      13.6%. CONCLUSION: Inspite of the relatively poor prognostic characteristics in
      the study population, gemcitabine and cisplatin, was an effective combination
      with tolerable, manageable toxicity in advanced NSCLC.

PMID- 15716992
TI  - Gemcitabine and cisplatin combination chemotherapy as a first-line treatment in
      patients with metastatic breast cancer.
AB  - PURPOSE: The objectives of this phase II prospective study were to evaluate the
      efficacy and toxicity of Gemcitabine plus cisplatin as a first line chemotherapy
      in female patients with metastatic breast cancer who previously received
      anthracyclin-based regimen as adjuvant chemotherapy. PATIENTS AND METHODS: Twenty
      five patients with metastatic and at least one bi-dimensionally measurable lesion
      were included in this study. Adequate bone marrow reserve, adequate hepatic and
      renal functions and performance status of < or = 2 were required. Patients have
      previously received anthracyclin based-chemotherapy as adjuvant. Treatment
      consisted of Gemcitabine 1250 mg/m2 on days 1 and 8 and cisplatin 75 mg/m2 on day
      1, cycles were repeated at 3-week intervals. RESULTS: 25 patients were evaluable
      for toxicity and 22 patients for response. Overall response was 54.5%. Complete
      response was reported in 13.6% of patients and partial response was reported in
      40.9% of patients. Six patients (27.2%) had stable disease and disease
      progression was reported in 18.2% of patients. Response was reported in all
      metastatic sites. Toxicities included grade 3, 4 vomiting in 32% and grade 3, 4
      neutropenia in 12%, grade 3, 4 thrombocytopenia in 32%. Only one case of
      neutropenic fever was reported. Renal and neurotoxicity was encountered in 12%
      and alopecia grade 1, 2 in 8% of patients. No treatment related death was
      reported. The median overall survival was 14.8 months (range: 2 to 18.5).
      CONCLUSION: Gemcitabine and cisplatin combination chemotherapy is active and well
      tolerated regimen for patients with metastatic breast cancer. This regimen
      represents a therapeutic option for patients receiving front line therapy for
      their metastatic breast cancer. Phase III randomized trial is needed for
      comparison with other 2nd line regimens to define the exact role of this
      combination.

PMID- 15716993
TI  - Near total laryngectomy: a versatile approach for voice restoration in advanced
      T3 and T4 laryngeal cancer: functional results and survival.
AB  - PURPOSE: Creation of a tunneled mucosal shunt between the trachea and pharynx
      that is controlled by remaining intrinsic laryngeal musculature with its nerve
      supply is an acceptable voice restoration procedure for advanced T3 and T4
      laryngeal cancer. Such a tunnel will allow unilateral direction of air from lung
      to pharynx during phonation and will prevent aspiration since deglutition is a
      vagal mediated response which will induce contraction of tubed laryngeal
      musculature preventing aspiration. We previously reported our preliminary
      experience with the technique and we adopted the voice restoration approach based
      on the concept of the near total laryngectomy thereafter. METHODS: Forty five
      patients with histologically proven squamous cell carcinoma of the larynx were
      included in this study (between January 1998 and February 2001). They were 42
      males and 3 females with a mean age of 52.6 years. Criteria for selection were a
      normal vocal process and arytenoid cartilage on the opposite side of the lesion
      as evidenced by endoscopy and CT scan with no major subglottic extension. In two
      patients supraglottic laryngectomy was carried out and in four other patients,
      complete tumor extirpation necessitated total laryngectomy. Accordingly, near
      total laryngectomy was carried out in the remaining 39 patients. Following a near
      total laryngectomy, where all laryngeal mucosa and cartilages are resected
      sparing the contralateral arytenoid cartilage with the overlying mucosa and
      surrounding musculature, the shunt was created by tubing the remaining mucosa
      with augmentation by pyriform sinus mucosa if necessary. The resulting tube was
      fashioned over 14 FG catheter for diameter control only and the remaining muscles
      were sutured over the tube. A permanent tracheostomy was established. Voice
      training was started postoperatively following resumption of oral feeding.
      RESULTS: Only one patient died in the immediate postoperative period due to
      massive myocardial infarction. One patient developed reactionary hemorrhage that
      was explored and controlled. Minor salivary fistula developed in nine patients
      (23.1%) and all were managed conservatively, none required intervention. Two
      patients (7.6%) had a retracted tracheostomy that required refashioning. Thirteen
      patients (33.3%) suffered transient aspiration that resolved spontaneously, non
      required intervention. Six patients developed recurrent disease (15.8%). The
      overall two year disease free survival was 76%. None of the cases developed
      laryngeal mucosal recurrences. Intelligible speech was achieved in 31 patients
      (81.6%). In the seven patients with shunt failure, insertion of a one way valve
      was successful in five patients in restoring a good quality voice. CONCLUSION:
      Near total laryngectomy is an oncologically safe procedure with acceptable
      complications that are well tolerated. It represents an ideal solution for
      patients with advanced T3 and T4 laryngeal cancer. Voice quality is very good and
      it does not require further management as is the case with prosthetic voice shunt
      valves.

PMID- 15716994
TI  - Extended lymphadenectomy to the lower paraaortic nodes during radical cystectomy.
AB  - PURPOSE: Evaluation of the diagnostic, prognostic and possible therapeutic role
      of extended lymphadenectomy to lower para-aortic area in operable bladder cancer
      patients. PATIENTS AND METHODS: One hundred and nine patients were subjected to
      the procedure in the National Cancer Institute of Cairo University, and in Minea
      Oncology Center, Ministry of Health by the same group of surgeons, during the
      period from September 2000 to March 2003. The lymph nodes dissected were labeled
      to the following groups: perivesical, lymph node of Cloquet, external iliac,
      internal iliac and obturator, common iliac and paraaortic groups both right and
      left. These nodes were subjected with the primary tumor to serial sectioning for
      histopathologic examination. Preoperatively, all patients were subjected to
      routine laboratory investigations. In addition to cystoscopy, biopsy and
      histologic examination, bone scan, chest X-ray and computerized tomography with
      I.V. contrast examination for the abdomen and pelvis were done for clinical
      staging of the disease. RESULTS: 34.4% of the node positive patients have been
      found to harbor the disease in the para-arotic lymph nodes above the common iliac
      bifurcation. Obturator, external iliac, internal iliac, para-aortic, common
      iliac, perivesical and lymph node of Cloquet are the higher incidence groups of
      positive lymph nodes sequentially. The clinical and C.T. staging are inaccurate
      methods of diagnosis due to high overall error up to 70.6% of patients. There is
      no higher incidence of morbidity, mortality, operative time or intraoperative
      blood loss related to the addition of lower para-arotic dissection to the routine
      radical cystectomy. CONCLUSION: Extension of lymphadenectomy to include the lower
      para-arotic area in addition to the standard pelvic lymphadenectomy during
      radical cystectomy for bladder cancer is a more accurate technique for diagnosis
      and staging of bladder cancer patients and it may help in determining the benefit
      of adjuvant chemotherapy +/- radiotherapy. By itself, it gives a better
      recurrence-free survival rate without adding higher morbidity or mortality than
      the standard pelvic lymphadenectomy.

PMID- 15716995
TI  - Functional evaluation of modified T pouch as ileal neobladder orthotopic
      reservoir.
AB  - BACKGROUND AND OBJECTIVE: We report on the functional results of orthotopic
      modified T pouch ileal neobladder, incorporating serous-lined extramural ileal
      antireflux technique for urinary diversion after radical cystectomy. MATERIAL AND
      METHODS: From September 1998 through November 2001, 42 patients of mean age of 49
      years (range 45-54) having invasive bladder carcinoma underwent radical
      cystectomy and orthotopic ileal neobladder urinary diversion, the modified T
      pouch. Thirty-three patients were males while the remaining 9 were females. The
      mean follow up was 24 months (range 18-42). Preoperative uni or bilateral
      ureteral dilatation was noted in 13/42 (30.9%) patients. Follow up included
      clinical examination, laboratory, radiological and urodynamic investigations.
      RESULTS: Early postoperative complications were recorded in 3 cases, that were
      managed conservatively. Day and night continence were achieved in 34/42 (81%) and
      29/42 (69%) patients, night enuresis in 2 (4.8%), while satisfactory day and
      night continence were noted, respectively. Upper urinary tract (UUT) remained
      unchanged or improved in all cases. No need for clean intermittent
      catheterization (CIC). No evidence of reflux was detected. Pressure at maximum
      capacity (average 17 cm H2O at 600 ml). Mean flow rate was 17.6 ml/sec (range 15
      24). Pelvic cancer recurrence was recorded in 5 patients at mean 24 months,
      respectively. CONCLUSIONS: Modified T pouch has an excellent functional criteria
      as an orthotopic ileal neobladder reservoir. It is absolutely indicated in short
      and/or massively dilated ureter.

PMID- 15716997
TI  - Ileocecal interpositional graft for gastric replacement after total gastrectomy.
AB  - PURPOSE: The aim of this study is to evaluate the technique of ileocecal segment
      interpositional graft after total gastrectomy for gastric cancer with assessment
      of its advantages and disadvantages. PATIENTS AND METHODS: This is a prospective
      study carried out at the National Cancer Institute, Cairo University. Twenty four
      patients with gastric carcinoma were identified from December 1998 to February
      2003. All of them were submitted to surgery after preoperative clinical,
      radiological and endoscopic diagnosis. Total gastrectomy with ileocecal
      interpositional graft were done (19 subdiaphragmatic reconstruction and 5
      intrathoracic reconstruction). Patients were followed up for at least 12 months
      for postoperative morbidity, body weight, reflux and dumping symptoms.
      Gastrografin swallow, barium swallow, upper GIT endoscopy were routinely done in
      all patients and pouch emptying time by Tc-99m sulpher colloid was done in 11
      patients only. RESULTS: Perioperative mortality was 8.3% (2/24). No patient
      reported reflux symptoms or showed endoscopic findings of reflux esophagitis in
      the subdiaphragmatic reconstruction group and mild reflux was noted in only one
      patient in the intrathoracic reconstruction group. No patient reported dumping
      symptoms. Emptying time showed good capacity as a reservoir of food.
      Postoperative decrease in body weight averaged less than 10% of preoperative
      weight. CONCLUSIONS: Ileocecal interposition graft after total gastrectomy has
      the advantages of preventing reflux esophagitis and providing functional
      replacement of the stomach as a reservoir for ingested food. It can be done with
      acceptable morbidity and mortality. It is simpler than some of the pouch
      reconstructions and deserves more attention.

PMID- 15716996
TI  - Management of parapharyngeal space tumors at the National Cancer Institute,
      Egypt.
AB  - PURPOSE: The purpose of this study is to evaluate parapharyngeal space (PPS)
      tumors as regards clinicopathological features, preoperative assessment,
      different surgical approaches, perioperative complications, patterns of
      recurrence and the role of non-surgical treatment. MATERIALS AND METHODS: This
      study included twenty-five patients with (PPS) tumors presented to NCI, Cairo
      University, from October 2001 to March 2003. The data of each patient included
      age, sex, presenting symptoms and signs, provisional diagnosis, preoperative
      investigations, operative data, histopathological examination, non-surgical
      treatment and state of follow up. All were collected and analyzed. RESULTS: This
      study included 12 males and 13 females. The mean age was 37.1 years. The main
      presenting symptom and sign was neck swelling. All patients were subjected to CT
      scan, while 9 patients had MRI. Nineteen patients underwent fine needle
      aspiration cytology (FNAC) which was conclusive in only 16 patients. Benign
      lesions were found in 12 patients (48%) and malignant lesions in 13 patients
      (52%). Parotid gland tumors (40%) and neurogenic tumors (16%) were the commonest.
      Surgical excision was done in 22 cases. There was no postoperative mortality and
      overall postoperative morbidity was 9% (2/22). Eight patients received
      postoperative radiotherapy. Three patients with lymphoma were treated with
      chemotherapy and two of them received involved field radiotherapy to the
      Waldyer's ring region. On follow up to 12-30 months, there were only one local
      and two distant recurrences in the malignant group. CONCLUSION: Surgery is the
      mainstay treatment for tumors of the (PPS). The addition of postoperative
      radiotherapy in certain indications in malignant tumors of the (PPS) will improve
      the local control.

PMID- 15716998
TI  - Lymph node metastasis in breast carcinoma: clinicopathological correlations in
      3747 patients.
AB  - BACKGROUND: Histological axillary node involvement (ANI) evaluated by axillary
      dissection remains the most accurate predictive factor for patients with invasive
      breast cancer. Axillary node involvement implies the necessity of systemic
      adjuvant treatment and locoregional irradiation. AIM OF THE STUDY: Is to detect
      the relative frequency of node positivity in relation to histopathology through
      studying a large mastectomy series. MATERIAL AND METHODS: This study included
      3747 mastectomy specimens performed at NCI, Cairo in the period 1993-2003. In
      each case we assessed the age at time of diagnosis, pathologic tumor size and
      number, histologic subtype (including grade), tumor location, number of lymph
      nodes dissected and number of positive nodes (burden of node positivity).
      RESULTS: Females constituted 96.8% of cases, 60.7% of them were premenopausal.
      The mean age was 47.1% +/- 10.5 years. Tumor size ranged from 0.5 to 20 cm. The
      global ANI rate in the entire cohort was 70.6%. In univariate analysis, five
      variables were significantly correlated to ANI, these were laterality,
      multiplicity, tumor size, histologic subtype and grade, while multiplicity, tumor
      size, histologic subtype and grade correlated significantly with metastatic
      burden. Multivariate analysis showed that older women (40-60 and > 60 years) have
      at least half the risk of developing LN metastasis compared to those < 40 years
      with the odds of 0.51 (0.35-0.73) and 0.31 (0.18-0.55), respectively. Tumor size
      > 2 cm put the women with breast cancer at 3 (if 2-5 cm) to 9 (if > 5 cm)folds of
      developing lymph node (LN) metastasis. Tumor size > 5 cm increases the likelihood
      of higher metastatic burden (> 3 +ve nodes) with odds of 1.5 (1.24-1.9).
      Unfavourable histology also increases the likelihood of more positive nodes to
      the double when compared to favourable histology. CONCLUSIONS: The results of
      this study reflected the unfortunate presentation of breast cancer patients. In
      addition, some factors could be used as useful guidelines in the management of
      those patients. These factors include age, tumor size and histologic type of the
      tumor.

PMID- 15716999
TI  - Clinical significance of vascular endothelial growth factor (VEGF) in sera of
      patients with pediatric malignancies.
AB  - BACKGROUND: Angiogenesis is essential for solid tumor growth. It is induced by
      tumor cells through stimulatory angiogenic peptides, one such peptide is vascular
      endothelial growth factor (VEGF). PURPOSE: The ultimate aim of the work is to
      investigate the possible role of VEGF as an early biomolecule involved in the
      progression of pediatric malignant tumors with high metastatic potential.
      PATIENTS AND METHODS: Forty-five pediatric patients were studied. They included
      four groups with malignant solid tumors suffering from Ewing's sarcoma,
      osteosarcoma, neuroblastoma and rhabdomyosarcoma. In addition, a healthy control
      group including fifteen age and sex matched children was included in the study.
      Serum VEGF levels were determined by ELISA technique. RESULTS: The level of VEGF
      was significantly higher in all types of solid tumors compared to normal healthy
      children. The mean values obtained for patients and controls were 429.44 +/-
      258.55 pg/ml and 79.36 +/- 63.81 pg/ml, respectively. No significant difference
      was detected in the level of VEGF among males and females. Also, no statistically
      significant difference was detected among the different types of malignant
      tumors. However, a marked significant difference was elucidated between
      metastatic and non-metastatic cancer patients, the values recorded were 753.33 +/
      173.64 pg/ml and 267.5 +/- 75.54 pg/ml, respectively (p < 0.001). Furthermore
      the results showed that 207 pg/ml of serum level of VEGF is the optimal cut-off
      value (mean +/- 2 SD of control) with sensitivity of 87% and specificity of 100%.
      Using the receiver operating characteristic (ROC) curve analysis,the area under
      the curve (0.917) indicated the validity of using serum VEGF level in the
      diagnosis of all different types of pediatric malignant solid tumors with high
      potentiality to metastasis. CONCLUSION: VEGF is an angiogenic stimulatory
      peptide. Its serum level could be a reliable marker in assessing pediatric
      malignancies with high metastatic potentials.

PMID- 15717000
TI  - Loss of heterozygosity at BRCA1, TP53, nm-23 and other loci on chromosome 17q in
      human breast carcinoma.
AB  - BACKGROUND: In Egypt, breast cancer ranks number one among the female
      malignancies. Activation of oncogenes and inactivation of tumor suppressor genes
      are thought to play an important role in the development and progression of
      breast cancer. PURPOSE: The present study is a trial to investigate the role of
      chromosome 17 in sporadic invasive ductal carcinoma of the breast through
      detection of LOH for 6 highly polymorphic microsatellite loci, two of which are
      located at BRCA1 gene (D17S855 and D17S856), one at TP53 gene, one at nm-23 gene
      and finally two at 17q12-12.3 (D17S183 and D17S250). MATERIAL AND METHODS: Tissue
      samples and their corresponding safety margin normal tissues were collected from
      25 patients with invasive ductal carcinoma of the breast of grades 2 and 3. LOH
      was detected for the 6 highly polymorphic microsatellite markers mentioned
      previously using PCR assay. RESULTS: The percentage of overall LOH recorded was
      68% of the cases examined. The highest LOH recorded in D17S855 and D17S856 (43%
      and 32% respectively), both markers are located at BRCA1 gene, followed by 32%
      LOH in nm-23 gene. D17S183 and D17S250, which are localised telomeric and
      centromeric to BRCA1 gene, showed 24% and 28% LOH, respectively. The lowest
      percentage of LOH was observed in the TP53 gene (14%). No significant correlation
      was found between each of the six markers used and lymph node status, grade, or
      menopausal status. LOH at the nm-23 marker exhibited a significant association
      with lymph node involvement. CONCLUSION: It can be concluded from the present
      study that BRCA1 gene may be involved in carcinogenesis of some sporadic breast
      cancer cases. Deletion in nm-23 gene is associated with advanced stage of the
      disease. Finally, another gene located at 17q12-12.3 region may be involved in
      some sporadic breast cancer cases.

PMID- 15717003
TI  - Mechanisms of neural cell death: implications for development of neuroprotective
      treatment strategies.
AB  - It has been increasingly recognized that cell death phenotypes and their
      molecular mechanisms are highly diverse. Necrosis is no longer considered a
      single entity, passively mediated by energy failure. Moreover, caspase-dependent
      apoptosis is not the only pathway involved in programmed cell death or even the
      only apoptotic mechanism. Recent experimental work emphasizes the diverse and
      interrelated nature of cell death mechanisms. Thus, there are both caspase
      dependent and caspase-independent forms of apoptosis, which may differ
      morphologically as well as mechanistically. There are also necrotic-like
      phenotypes that require de novo protein synthesis and are, therefore, forms of
      programmed cell death. In addition, forms of cell death showing certain
      morphological features of both necrosis and apoptosis have been identified,
      leading to the term aponecrosis. Considerable experimental evidence also shows
      that modulation of one form of cell death may lead to another. Together, these
      observations underscore the need to substantially revise our conceptions about
      neuroprotection strategies. Use of multiple treatments that target different cell
      death cascades, or single agents that moderate multiple cell death pathways, is
      likely to lead to more effective neuroprotection for clinical disorders.

PMID- 15717004
TI  - Neuronal death/survival signaling pathways in cerebral ischemia.
AB  - Cumulative evidence suggests that apoptosis plays a pivotal role in cell death in
      vitro after hypoxia. Apoptotic cell death pathways have also been implicated in
      ischemic cerebral injury in in vivo ischemia models. Experimental ischemia and
      reperfusion models, such as transient focal/global ischemia in rodents, have been
      thoroughly studied and the numerous reports suggest the involvement of cell
      survival/death signaling pathways in the pathogenesis of apoptotic cell death in
      ischemic lesions. In these models, reoxygenation during reperfusion provides a
      substrate for numerous enzymatic oxidation reactions. Oxygen radicals damage
      cellular lipids, proteins and nucleic acids, and initiate cell signaling pathways
      after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and
      factors in the signaling pathways has provided substantial understanding of the
      mechanisms involved in cell death/survival signaling pathways and the role of
      oxygen radicals in ischemic cerebral injury. Future studies of these pathways may
      provide novel therapeutic strategies in clinical stroke.

PMID- 15717006
TI  - Neuroprotection for ischemic stroke: two decades of success and failure.
AB  - Alteplase (rt-PA) is the first therapy successfully developed for acute stroke
      therapy. The success of rt-PA spurred development of new avenues for acute stroke
      management. For the last two decades, a great deal of attention has been paid to
      neuroprotective therapies. Initial preclinical studies demonstrated numerous
      drugs are effective for treating acute stroke in animal models; however,
      subsequent clinical trials have been frustrating, and none of the agents has
      proven effective. The various outcomes of preclinical and clinical trials have
      been the subject of much discussion. In this article, we review some key
      neuroprotective trials and the possible reasons for their failures. By
      identifying the discrepancies between preclinical studies and clinical trials, we
      may be able to set guidelines for future effective trials.

PMID- 15717005
TI  - Hypoxic preconditioning protects against ischemic brain injury.
AB  - Animals exposed to brief periods of moderate hypoxia (8% to 10% oxygen for 3
      hours) are protected against cerebral and cardiac ischemia between 1 and 2 days
      later. This hypoxia preconditioning requires new RNA and protein synthesis. The
      mechanism of this hypoxia-induced tolerance correlates with the induction of the
      hypoxia-inducible factor (HIF), a transcription factor heterodimeric complex
      composed of inducible HIF-1alpha and constitutive HIF-1beta proteins that bind to
      the hypoxia response elements in a number of HIF target genes. Our recent studies
      show that HIF-1alpha correlates with hypoxia induced tolerance in neonatal rat
      brain. HIF target genes, also induced following hypoxia-induced tolerance,
      include vascular endothelial growth factor, erythropoietin, glucose transporters,
      glycolytic enzymes, and many other genes. Some or all of these genes may
      contribute to hypoxia-induced protection against ischemia. HIF induction of the
      glycolytic enzymes accounts in part for the Pasteur effect in brain and other
      tissues. Hypoxia-induced tolerance is not likely to be equivalent to treatment
      with a single HIF target gene protein since other transcription factors including
      Egr-1 (NGFI-A) have been implicated in hypoxia regulation of gene expression.
      Understanding the mechanisms and genes involved in hypoxic tolerance may provide
      new therapeutic targets to treat ischemic injury and enhance recovery.

PMID- 15717007
TI  - Clinical trials for cytoprotection in stroke.
AB  - To date, many cytoprotective drugs have reached the stage of pivotal phase 3
      efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the
      neuroprotective literature, the phrase "failure to demonstrate efficacy" prevails
      as a common thread among the many neutral or negative trials, despite the largely
      encouraging results encountered in preclinical studies. The reasons for this
      discrepancy are multiple, and have been discussed by Dr. Zivin in his review.
      Many of the recent trials have addressed deficiencies of the previous ones with
      more rigorous trial design, including more specific patient selection criteria
      (ensure homogeneity of stroke location and severity), stratified randomization
      algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic
      monitoring. Current trials have also incorporated biologic surrogate markers of
      toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal
      therapies and coupled cytoprotection/reperfusion strategies are being
      investigated to optimize tissue salvage. This review will focus on individual
      therapeutic strategies and we will emphasize what we have learned from these
      trials both in terms of trial design and the biologic effect (or lack thereof) of
      these agents.

PMID- 15717008
TI  - Critical appraisal of neuroprotection trials in head injury: what have we
      learned?
AB  - To date, despite very encouraging preclinical results, almost all phase II/III
      clinical neuroprotection trials in traumatic brain injury (TBI) have failed to
      show any consistent improvement in outcome for TBI patients. To understand the
      reasons behind such developments we need to review and evaluate the evolution of
      trial design as a result of our changing understanding of the pathophysiology of
      brain cell death and progress of translational research from the laboratory bench
      to the bedside. This paper attempts to critically appraise these neuroprotection
      trials, rationalize the paucity of effectiveness, review any recent developments
      in the field, and try to draw some conclusions on how to move forward.

PMID- 15717010
TI  - Failures and successes of NMDA receptor antagonists: molecular basis for the use
      of open-channel blockers like memantine in the treatment of acute and chronic
      neurologic insults.
AB  - Excitotoxicity, defined as excessive exposure to the neurotransmitter glutamate
      or overstimulation of its membrane receptors, has been implicated as one of the
      key factors contributing to neuronal injury and death in a wide range of both
      acute and chronic neurologic disorders. Excitotoxic cell death is due, at least
      in part, to excessive activation of N-methyl-D-aspartate (NMDA)-type glutamate
      receptors and hence excessive Ca2+ influx through the receptor's associated ion
      channel. Physiological NMDA receptor activity, however, is also essential for
      normal neuronal function; potential neuroprotective agents that block virtually
      all NMDA receptor activity will very likely have unacceptable clinical side
      effects. For this reason many NMDA receptor antagonists have disappointingly
      failed advanced clinical trials for a number of diseases including stroke and
      neurodegenerative disorders such as Huntington's disease. In contrast, studies in
      my laboratory were the first to show that memantine, an adamantane derivative,
      preferentially blocks excessive NMDA receptor activity without disrupting normal
      activity. Memantine does this through its action as an open-channel blocker; it
      enters the receptor-associated ion channel preferentially when it is excessively
      open, and, most importantly, its off-rate is relatively fast so that it does not
      substantially accumulate in the channel to interfere with normal synaptic
      transmission. Past clinical use for other indications has demonstrated that
      memantine is well tolerated, and it has recently been approved in both Europe and
      the USA for the treatment of dementia of the Alzheimer's type. Clinical studies
      of the safety and efficacy of memantine for other neurological disorders,
      including glaucoma and other forms of dementia, are currently underway. A series
      of second-generation memantine derivatives are currently in development and may
      prove to have even greater neuroprotective properties than does memantine. These
      second-generation drugs take advantage of the fact that the NMDA receptor has
      other modulatory sites, in addition to its ion channel, that could potentially be
      used for safe but effective clinical intervention.

PMID- 15717009
TI  - Neuroprotection and acute spinal cord injury: a reappraisal.
AB  - It has long been recognized that much of the post-traumatic degeneration of the
      spinal cord following injury is caused by a multi-factorial secondary injury
      process that occurs during the first minutes, hours, and days after spinal cord
      injury (SCI). A key biochemical event in that process is reactive oxygen-induced
      lipid peroxidation (LP). In 1990 the results of the Second National Acute Spinal
      Cord Injury Study (NASCIS II) were published, which showed that the
      administration of a high-dose regimen of the glucocorticoid steroid
      methylprednisolone (MP), which had been previously shown to inhibit post
      traumatic LP in animal models of SCI, could improve neurological recovery in
      spinal-cord-injured humans. This resulted in the registration of high-dose MP for
      acute SCI in several countries, although not in the U.S. Nevertheless, this
      treatment quickly became the standard of care for acute SCI since the drug was
      already on the U.S. market for many other indications. Subsequently, it was
      demonstrated that the non-glucocorticoid 21-aminosteroid tirilazad could
      duplicate the antioxidant neuroprotective efficacy of MP in SCI models, and
      evidence of human efficacy was obtained in a third NASCIS trial (NASCIS III). In
      recent years, the use of high-dose MP in acute SCI has become controversial
      largely on the basis of the risk of serious adverse effects versus what is
      perceived to be on average a modest neurological benefit. The opiate receptor
      antagonist naloxone was also tested in NASCIS II based upon the demonstration of
      its beneficial effects in SCI models. Although it did not a significant overall
      effect, some evidence of efficacy was seen in incomplete (i.e., paretic)
      patients. The monosialoganglioside GM1 has also been examined in a recently
      completed clinical trial in which the patients first received high-dose MP
      treatment. However, GM1 failed to show any evidence of a significant enhancement
      in the extent of neurological recovery over the level afforded by MP therapy
      alone. The present paper reviews the past development of MP, naloxone, tirilazad,
      and GM1 for acute SCI, the ongoing MP-SCI controversy, identifies the regulatory
      complications involved in future SCI drug development, and suggests some
      promising neuroprotective approaches that could either replace or be used in
      combination with high-dose MP.

PMID- 15717011
TI  - Prophylactic activation of neuroprotective stress response pathways by dietary
      and behavioral manipulations.
AB  - It is well established that when most types of cells, including neurons, are
      exposed to a mild stress they increase their ability to resist more severe
      stress. This "preconditioning" phenomenon involves up-regulation of genes that
      encode cytoprotective proteins such as heat-shock proteins and growth factors. We
      found that a similar beneficial cellular stress response can be induced in
      neurons throughout the brain by a "meal-skipping" dietary restriction (DR)
      regimen in rats and mice. DR is effective in protecting neurons and improving
      functional outcome in models of stroke, Alzheimer's, Parkinson's and Huntington's
      diseases. DR induces an increase in the levels of brain-derived neurotrophic
      factor (BDNF) and heat-shock proteins in neurons. DR also stimulates neurogenesis
      in the hippocampus, and BDNF plays a role in this effect of DR. Physical exercise
      and environmental enrichment are two other manipulations that have been shown to
      induce BDNF expression in the brain, presumably because it is a mild cellular
      stress. When taken together with epidemiological and clinical studies in humans,
      the data from animal studies suggest that it may be possible to reduce the risk
      for age-related neurodegenerative disorders through dietary and behavioral
      modifications that act by promoting neuronal plasticity and survival.

PMID- 15717012
TI  - Neuroprotective strategies in Alzheimer's disease.
AB  - In addition to strategies designed to decrease amyloid beta (A beta) levels, it
      is likely that successful Alzheimer's disease (AD) therapeutic regimens will
      require the concomitant application of neuroprotective agents. Elucidation of
      pathophysiological processes occurring in AD and identification of the molecular
      targets mediating these processes point to potential high-yield neuroprotective
      strategies. Candidate neuroprotective agents include those that interact
      specifically with neuronal targets to inhibit deleterious intraneuronal
      mechanisms triggered by A beta and other toxic stimuli. Strategies include
      creating small molecules that block A beta interactions with cell surface and
      intracellular targets, down-regulate stress kinase signaling cascades, block
      activation of caspases and expression of pro-apoptotic proteins, and inhibit
      enzymes mediating excessive tau protein phosphorylation. Additional potential
      neuroprotective compounds include those that counteract loss of cholinergic
      function, promote the trophic state and plasticity of neurons, inhibit
      accumulation of reactive oxygen species, and block excitotoxicity. Certain
      categories of compounds, such as neurotrophins or neurotrophin small molecule
      mimetics, have the potential to alter neuronal signaling patterns such that
      several of these target actions might be achieved by a single agent.

PMID- 15717013
TI  - The paradigm of Huntington's disease: therapeutic opportunities in
      neurodegeneration.
AB  - Despite a relatively small number of affected patients, Huntington's disease (HD)
      has been a historically important disease, embodying many of the major themes in
      modern neuroscience, including molecular genetics, selective neuronal
      vulnerability, excitotoxicity, mitochondrial dysfunction, apoptosis, and
      transcriptional dysregulation. The discovery of the HD gene in 1993 opened the
      door to the mechanisms of HD pathogenesis. Multiple pathologic mechanisms have
      been discovered, each one serving as a potential therapeutic target. HD thus
      continues to serve as a paradigmatic disorder, with basic bench research
      generating clinically relevant insights and stimulating the development of
      therapeutic human trials.

PMID- 15717015
TI  - New developments in magnetic resonance imaging of the brain.
AB  - Magnetic resonance imaging (MRI) continues to have a large impact on the
      diagnosis and management of a number of diseases, especially diseases associated
      with brain injury. The strengths of MRI are the unique contrast that can be
      obtained, and the fact that it is not harmful and that it can be readily applied
      to human and animal models. The past decade has seen development of functional
      MRI techniques that measure aspects of hemodynamics and water diffusion that are
      playing an important role. Indeed, these techniques are having a major impact on
      management of brain injury. The development of MRI continues at a rapid pace and
      a renewed push to increased spatial and temporal resolution will extend the
      applicability of anatomical and functional MRI. Increased interest in molecular
      imaging using MRI is increasing the number of processes that can be imaged in the
      brain. This work reviews some new developments that are being made in anatomical,
      functional, and molecular MRI of the brain, with comments about usefulness for
      work in the area of neuroprotection.

PMID- 15717016
TI  - Strategic challenges in neurotherapeutic pharmaceutical development.
AB  - Developing new therapeutics presents formidable economic, scientific, and medical
      challenges that are exacerbated by special factors in neurotherapeutics
      development, e.g., the complexity of the CNS with its attendant need to sometimes
      affect multiple pathways, the lack of clarity of disease etiology, inadequacy of
      available animal models, and difficulties in defining disease populations and
      quantifying treatment response. This paper reviews the economic challenges faced
      by therapeutics developers in general and neurotherapeutics developers in
      particular. It discusses key scientific challenges, particularly those pertinent
      to neurotherapeutics development, as a background to proposing a different
      industrial strategy to drive future therapeutics development. This Biodesign
      strategy potentially surpasses previous paradigms by incorporating elements such
      as the use of disease modeling to select better targets and potential therapies,
      information science-based approaches to enhance small molecule chemistry,
      exploitation of the potential for biological technologies to rapidly generate
      mechanistic probes, and development of improved approaches for using animal
      models and studying human molecules mechanistically and biologically. Synergistic
      use of these elements can change the overall business model of companies engaged
      in neurotherapeutics development. The Biodesign paradigm has the potential to
      both markedly enhance the development of new therapies and to address some of the
      economic challenges facing healthcare systems and therapeutics developers alike.

PMID- 15717014
TI  - Neurodegeneration and neuroprotection in Parkinson disease.
AB  - Many of the motoric features that define Parkinson disease (PD) result primarily
      from the loss of the neuromelanin (NM)-containing dopamine (DA) neurons of the
      substantia nigra (SN), and to a lesser extent, other mostly catecholaminergic
      neurons, and are associated with cytoplasmic "Lewy body" inclusions in some of
      the surviving neurons. While there are uncommon instances of familial PD, and
      rare instances of known genetic causes, the etiology of the vast majority of PD
      cases remains unknown (i.e., idiopathic). Here we outline genetic and
      environmental findings related to PD epidemiology, suggestions that aberrant
      protein degradation may play a role in disease pathogenesis, and pathogenetic
      mechanisms including oxidative stress due to DA oxidation that could underlie the
      selectivity of neurodegeneration. We then outline potential approaches to
      neuroprotection for PD that are derived from current notions on disease
      pathogenesis.

PMID- 15717018
TI  - Biomarkers: potential uses and limitations.
AB  - Biomarkers provide a dynamic and powerful approach to understanding the spectrum
      of neurological disease with applications in observational and analytic
      epidemiology, randomized clinical trials, screening and diagnosis and prognosis.
      Defined as alterations in the constituents of tissues or body fluids, these
      markers offer the means for homogeneous classification of a disease and risk
      factors, and the can extend our base information about the underlying
      pathogenesis of disease. Biomarkers can also reflect the entire spectrum of
      disease from the earliest manifestations to the terminal stages. This brief
      review describes the major uses of biomarkers in clinical investigation. Careful
      assessment of the validity of biomarkers is required with respect to the stage of
      disease. Causes of variability in the measurement of biomarkers range from the
      individual to the laboratory. Issues that affect the analysis of biomarkers are
      discussed along with recommendations on how to deal with bias and confounding.

PMID- 15717019
TI  - Biomarkers and surrogate markers: an FDA perspective.
AB  - Interest is increasing rapidly in the use of surrogate markers as primary
      measures of the effectiveness of investigational drugs in definitive drug trials.
      Many such surrogate markers have been proposed as potential candidates for use in
      definitive effectiveness trials of agents to treat neurologic or psychiatric
      disease, but as of this date, there are no such markers that have been adequately
      "validated," that is, shown to predict the effect of the treatment on the
      clinical outcome of interest. While the current law and regulations permit the
      United States Food and Drug Administration to base the approval of a drug product
      on a determination the effect of the drug on an unvalidated surrogate marker
      (that is, one for which it is not known that an effect on the surrogate actually
      predicts the desired clinical benefit), there are a number of difficulties in
      interpreting trials that use surrogate markers as primary measures of drug
      effect. In this article, the relevant regulatory context will be discussed, as
      well as the epistemological problems related to the interpretation of clinical
      trials in which unvalidated surrogate markers are used as primary outcomes.

PMID- 15717020
TI  - Quantitative magnetic resonance techniques as surrogate markers of Alzheimer's
      disease.
AB  - Recent advances in understanding the molecular biology of Alzheimer's disease
      (AD) offer the promise of useful therapeutic intervention in the foreseeable
      future. Hence, improved methods for early diagnosis and noninvasive surrogates of
      disease severity in AD have become more imperative. Various quantitative magnetic
      resonance (MR) techniques that measure the anatomic, biochemical,
      microstructural, functional, and blood-flow changes are being evaluated as
      possible surrogate measures of disease progression. Cross-sectional and
      longitudinal studies indicate that MR-based volume measurements are potential
      surrogates of disease progression in AD, starting from the preclinical stages.
      The validity of MR-based volumetry as a surrogate marker for therapeutic efficacy
      in AD remains to be tested in a positive disease-modifying drug trial. Recent
      development of amyloid imaging tracers for positron emission tomography has been
      a major breakthrough in the field of imaging markers for AD. Efforts to image
      plaques are also underway in MR imaging. As with indirect MR measures, these
      approaches of directly imaging the pathological substrate will need to undergo a
      validation process with longitudinal studies to prove their usefulness as
      surrogate markers in AD.

PMID- 15717021
TI  - Molecular neuroimaging in Alzheimer's disease.
AB  - Considerable data exist to support the use of positron emission tomography (PET)
      and single photon emission computed tomography (SPECT) scanning as biomarkers for
      Alzheimer's disease (AD). The techniques are reasonably sensitive and specific in
      differentiating AD from normal aging, and recent studies with pathological
      confirmation show good sensitivity and specificity in differentiating AD from
      other dementias. These techniques also can detect abnormalities in groups of
      asymptomatic and presymptomatic individuals and may be able to predict decline to
      dementia. However, there are a number of existing questions related to the use of
      these techniques in samples that are fully representative of the spectrum of
      patients with dementia. For example, it is unclear how well PET and SPECT perform
      in comparison to a clinical diagnosis obtained in the same patient group, when
      autopsy is used as a gold standard. It will also be important to know what PET
      and SPECT add to the certainty of diagnosis in addition to the standard clinical
      diagnosis. Despite these unanswered questions, PET and SPECT may have application
      as biomarkers for AD in a number of clinical and research settings, especially in
      academic centers, where most of the existing studies have been done.

PMID- 15717022
TI  - Cerebrospinal fluid protein biomarkers for Alzheimer's disease.
AB  - The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic
      treatment of Alzheimer's disease (AD) has made patients seek medical advice at an
      earlier stage of the disease. This has highlighted the importance of diagnostic
      markers for early AD. However, there is no clinical method to determine which of
      the patients with mild cognitive impairment (MCI) will progress to AD with
      dementia, and which have a benign form of MCI without progression. In this paper,
      the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is
      reviewed. The diagnostic performance of the three biomarkers, total tau, phospho
      tau, and the 42 amino acid form of beta-amyloid have been evaluated in numerous
      studies and their ability to identify incipient AD in MCI cases has also been
      studied. Some candidate AD biomarkers including ubiquitin, neurofilament
      proteins, growth-associated protein 43 (neuromodulin), and neuronal thread
      protein (AD7c) show interesting results but have been less extensively studied.
      It is concluded that CSF biomarkers may have clinical utility in the
      differentiation between AD and several important differential diagnoses,
      including normal aging, depression, alcohol dementia, and Parkinson's disease,
      and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly
      progressive dementia. Early diagnosis of AD is not only of importance to be able
      to initiate symptomatic treatment with AChE inhibitors, but will be the basis for
      initiation of treatment with drugs aimed at slowing down or arresting the
      degenerative process, such as gamma-secretase inhibitors, if these prove to
      affect AD pathology and to have a clinical effect.

PMID- 15717023
TI  - Biomarkers of Alzheimer disease in plasma.
AB  - Plasma and serum biochemical markers proposed for Alzheimer disease (AD) are
      based on pathophysiologic processes such as amyloid plaque formation [amyloid
      beta-protein (A beta), A beta autoantibodies, platelet amyloid precursor protein
      (APP) isoforms], inflammation (cytokines), oxidative stress (vitamin E,
      isoprostanes), lipid metabolism (apolipoprotein E, 24S-hydroxycholesterol), and
      vascular disease [homocysteine, lipoprotein (a)]. Most proteins or metabolites
      evaluated in plasma or serum thus far are, at best, biological correlates of AD:
      levels are statistically different in AD versus controls in some cohorts, but
      they lack sensitivity or specificity for diagnosis or for tracking response to
      therapy. Approaches combining panels of existing biomarkers or surveying the
      range of proteins in plasma (proteomics) show promise for discovering biomarker
      profiles that are characteristic of AD, yet distinct from nondemented patients or
      patients with other forms of dementia.

PMID- 15717024
TI  - Genetics of Parkinson disease.
AB  - Parkinson disease (PD) is the second most common neurodegenerative disorder.
      Recent studies have consistently demonstrated that in some families, disease is
      attributable to a mutation in a single gene. To date, genetic analyses have
      detected linkage to six chromosomal regions and have identified three causative
      genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1). In addition,
      mutations in several other genes have been implicated in familial PD.
      Identification of the mutations in these genes has led to the recognition that
      the ubiquitin-proteasome system is an important pathway that may be disrupted in
      PD. Studies are ongoing to identify additional genes that may contribute to PD
      susceptibility, particularly in late-onset families without a clear pattern of
      disease inheritance. With the identification of mutations in particular genes and
      the likely role of additional genes that are important in PD risk-susceptibility,
      appropriate protocols must be developed so that accurate and informative genetic
      counseling can be offered to families in which one or more members has PD.
      Further diagnostic testing should be delayed until more is learned about the
      frequency, penetrance, and risk assessment of certain gene mutations. Important
      lessons can be learned from the implementation of counseling protocols for other
      neurodegenerative disorders, such as Huntington disease and Alzheimer disease.

PMID- 15717025
TI  - Neuroimaging in Parkinson's disease.
AB  - In this review, the potential role of positron emission tomography and single
      photon emission computed tomography as biological markers for diagnosing and
      following the progression of Parkinson's disease (PD) is discussed. Their value
      for assessing the efficacy of putative neuroprotective agents in PD and for
      revealing the pharmacological changes underlying the symptomatology and
      complications of this disorder is also considered. It is concluded that in the
      future functional imaging will provide a valuable adjunct to clinical assessment
      when judging the efficacy of putative neuroprotective approaches to PD.

PMID- 15717026
TI  - Huntington's disease genetics.
AB  - Huntington's disease (HD) is a dominantly transmitted neurodegenerative disorder
      with wide variation in onset age but with an average age at onset of 40 years.
      Children of HD gene carriers have a 50% chance of inheriting the disease. The
      characteristic symptoms of HD are involuntary choreiform movements, cognitive
      impairment, mood disorders, and behavioral changes which are chronic and
      progressive over the course of the illness. HD is a "trinucleotide repeat"
      disorder, which is caused by an increase in the number of CAG repeats in the HD
      gene. Repeats of 40 or larger are associated with disease expression, whereas
      repeats of 26 and smaller are normal. Intermediate numbers of repeats, between 27
      and 35, are not associated with disease expression but may expand in paternal
      transmission, resulting in the disease in descendents. Repeats of 36-39 are
      associated with reduced penetrance whereby some develop HD and others do not. The
      identification of the genetic defect in HD permits direct genetic testing for the
      presence of the gene alteration responsible for the disease. Tests may be
      performed in three circumstances: (1) confirmation of diagnosis, (2) predictive
      testing of persons at genetic risk for inheriting HD, and (3) prenatal testing.
      Testing is widely available and much experience has been gained with protocols
      that assist the individual in making an informed choice about test options, and
      minimize the occurrence of adverse emotional outcomes.

PMID- 15717027
TI  - Using advances in neuroimaging to detect, understand, and monitor disease
      progression in Huntington's disease.
AB  - Transgenic mouse models and other screens are being used to identify potential
      therapeutic agents for use in clinical trials in Huntington's disease (HD). The
      development of surrogate markers that can be used in clinical therapeutics is an
      active area of research. Because HD is relatively uncommon and only a portion of
      available subjects meet inclusion and exclusion criteria, therapeutic trials are
      limited by the availability of potential subjects as well as the relative
      insensitivity of the clinical measures used. Neuroimaging methods offer the
      potential to provide noninvasive, reproducible, and objective methods not only to
      better understand the disease process but also to follow in clinical studies to
      determine if a drug is effective in slowing down disease progression or perhaps
      even in delaying onset. Following is a review of the literature, which highlights
      the studies that have been published to date.

PMID- 15717030
TI  - Evidence-based neurotherapeutics: a spectrum of evidence.

PMID- 15717029
TI  - Biomarkers and surrogate outcomes in neurodegenerative disease: lessons from
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic disease of the CNS that most commonly
      affects young adults. It is usually characterized in the early years by acute
      relapses followed by partial or complete remission; in later years progressive
      and irreversible disability develops. Because of the protracted and unpredictable
      clinical course, biological surrogate markers are much needed to make clinical
      trials of potential disease-modifying treatments more efficient. Magnetic
      resonance (MR) outcome measures are now widely used to monitor treatment outcome
      in MS trials. Areas of multifocal inflammation are detected with a high
      sensitivity as new areas of gadolinium enhancement and T2 abnormality, and these
      may be considered as surrogate markers for clinical relapses. However,
      progressive disability is not clearly related to inflammatory lesions but rather
      to a progressive and diffuse process with increasing neuroaxonal loss. MR
      surrogate measures for neuroaxonal loss include atrophy (tissue loss in brain and
      spinal cord), N-acetyl aspartate, and T1 hypointense lesions. Diffuse abnormality
      in normal appearing brain tissue may also be monitored using magnetization
      transfer ratio and other quantitative MR measures. For treatment trials of new
      agents aimed at preventing disability, measures of neuroaxonal damage should be
      acquired, especially atrophy, which occurs at all stages of MS and which can be
      quantified in a sensitive and reproducible manner. Because the MR surrogates for
      neuroaxonal loss are not yet validated as predicting future disability,
      definitive trials should continue to monitor an appropriate disability endpoint.

PMID- 15717028
TI  - Measures and markers in amyotrophic lateral sclerosis.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized
      by loss of spinal and cortical motor neurons, leading to progressive weakness and
      ultimately, death. Clinically, there appears to be an anatomic focus at disease
      onset, from which the disease then spreads. Because the focus of initial symptoms
      and the subsequent direction of spread can vary from patient to patient, disease
      monitoring is difficult, especially in a clinical trial, in which outcome
      measures must be identical and able to capture progression of all types. Thus,
      the search for markers of disease progression is especially important in ALS.
      Many approaches have been taken, from voluntary strength assessment and
      functional rating scales to physiological and pathological sampling of affected
      portions of nervous system. No proposed marker has been demonstrated to meet the
      desired criteria of biological meaning, sensitivity to disease progression, clear
      relationship to overall prognosis and survival, and ease of measurement. However,
      progress is being made in all of these regards.

PMID- 15717031
TI  - Translating therapies for Huntington's disease from genetic animal models to
      clinical trials.
AB  - Genetic animal models of inherited neurological diseases provide an opportunity
      to test potential treatments and explore their promise for translation to humans
      experiencing these diseases. Therapeutic trials conducted in mouse models of
      Huntington's disease have identified a growing number of potential therapies that
      are candidates for clinical trials. Although it is very exciting to have these
      candidates, there has been increasing concern about the feasibility and
      desirability of taking all of the compounds that may work in mice and testing
      them in patients with HD. There is a need to begin to prioritize leads emerging
      from transgenic mouse studies; however, it is difficult to compare results
      between compounds and laboratories, and there are also many additional factors
      that can affect translation to humans. Among the important issues are what
      constitutes an informative genetic model, what principals should be followed in
      designing and conducting experiments using genetic animal models, how can results
      from different laboratories and in different models be compared, what body of
      evidence is desirable to fully inform clinical decision making, and what factors
      contribute to the equipoise in determining whether preclinical information about
      a therapy makes clinical study warranted. In the context of Huntington's disease,
      we will review the current state of genetic models and their successes in putting
      forward therapeutic leads, provide a guide to assessing studies in mouse models,
      and discuss some of the salient issues related to translation from mice to
      humans.

PMID- 15717032
TI  - FDA: evidentiary standards for drug development and approval.
AB  - The United States Food and Drug Administration is charged with approving drug
      treatments that have been shown to be safe and effective. Relevant statutes and
      regulations provide a legal framework for establishing safety and effectiveness
      that is sufficiently flexible to ensure that appropriate scientific data are
      collected for specific treatments targeted to particular diseases. Nonetheless,
      all clinical trials proposed to establish effectiveness must incorporate common
      elements in order for the appropriate legal and scientific standards of drug
      approval to be met. This article will discuss the relevant laws and regulations
      pertaining to the current effectiveness standard and will discuss the most
      important clinical trial design elements currently considered acceptable for
      applications for treatments of neurologic and psychiatric illness.

PMID- 15717033
TI  - Funding evidence: the National Institute of Neurological Disorders and Stroke
      Clinical Trials Program.
AB  - The goal of the National Institute of Neurological Disorders and Stroke (NINDS)
      Clinical Trials Program is to foster clinical trials that will provide the
      evidence needed to inform clinical care. The NINDS currently supports clinical
      research in over 150 neurological disorders. The rapid pace of preclinical
      discovery and the diversity of neurological diseases, however, present challenges
      for clinical trials. There is a growing number of potential interventions to be
      tested in clinical trials. The NINDS Clinical Trials program is therefore
      exploring ways of making drug selection for clinical trials more evidence-based.
      Additionally, NINDS supports pilot clinical trials that focus on the timely and
      efficient testing of agents to determine if resource-intensive comparative
      efficacy trials are warranted. In concert with the National Institutes of Health
      Roadmap, NINDS is planning to expand clinical trials infrastructure. This
      infrastructure is intended to enable the conduct of clinical trials for rare
      diseases and diseases without previous trials experience and facilitate the
      recruitment of a broad range of participants. Rigorous programs to select agents,
      and design and monitor clinical trials will encourage the efficient use of this
      clinical trials infrastructure and will ensure that NINDS-funded studies meet the
      highest scientific and ethical standards.

PMID- 15717034
TI  - Evidence from biomarkers and surrogate endpoints.
AB  - The use of physiological, anatomical, and other biological tests is commonplace
      in the practice of medicine. In neurology, objectively measured tests termed
      biomarkers (BMs) are playing an increasing role in diagnosis and management of
      disease, both in clinical practice and in experimental therapeutics. This article
      will discuss the various applications of BMs to the assessment of therapies for
      neurological diseases and will use examples from neurological diseases to
      elucidate the strengths and potential weaknesses of BMs. As the understanding of
      the pathophysiology of many neurological diseases has improved, new BMs have been
      developed, and efforts have been made to use these as proxies for clinical
      endpoints. A BM used in this manner is referred to as a surrogate endpoint (SE).
      There are many potential advantages and disadvantages of using SEs in the
      evaluation of new therapies, and these will be reviewed as well. Furthermore, the
      evidence required for the development of an SE and the nature of the evidence
      that can be derived from the use of BMs and SEs will be discussed.

PMID- 15717035
TI  - From evidence to action.
AB  - Despite the availability of vast quantities of evidence from basic biomedical and
      clinical studies, a gap often exists between the optimal practice suggested by
      the evidence and actual practice. For many clinical situations, however, evidence
      is unavailable, of poor quality or contradictory. Out of necessity, clinicians
      have become accustomed to relying on non-evidence-based tools to make decisions.
      Out of habit, they rely on these tools even when high-quality evidence becomes
      available. Growing out of an increasing awareness of this problem, the evidence
      based medicine (EBM) movement sought to empower clinicians to find the evidence
      most relevant to a specific clinical question. Various organizations have used
      EBM techniques to develop systematic reviews and practice guidelines to aid
      physicians in making evidence-based decisions. A systematic review follows a
      process of asking a clinical question, finding the relevant evidence, critically
      appraising the evidence and formulating conclusions and recommendations. Results
      are mixed on whether educating physicians about evidence-based recommendations is
      sufficient to change physician behavior. Barriers to adopting evidence-based best
      practice remain, including physician skepticism, patient expectations, fear of
      legal action, and distorted reimbursement systems. Additionally, despite enormous
      research efforts there remains a lack of high-quality evidence to guide care for
      many clinical situations.

PMID- 15717036
TI  - Observational versus experimental studies: what's the evidence for a hierarchy?
AB  - The tenets of evidence-based medicine include an emphasis on hierarchies of
      research design (i.e., study architecture). Often, a single randomized,
      controlled trial is considered to provide "truth," whereas results from any
      observational study are viewed with suspicion. This paper describes information
      that contradicts and discourages such a rigid approach to evaluating the quality
      of research design. Unless a more balanced strategy evolves, new claims of
      methodological authority may be just as problematic as the traditional claims of
      medical authority that have been criticized by proponents of evidence-based
      medicine.

PMID- 15717037
TI  - Evidence from cost-effectiveness research.
AB  - Economic evaluations are a set of outcomes and health services research methods
      to inform the debate about the rising cost of health care and include cost-of
      illness studies and cost-effectiveness research. Cost-effectiveness research is
      the comparative analysis of two or more alternative interventions in terms of
      their health and economic consequences, whose results are expressed as an
      incremental cost-effectiveness ratio, the ratio of differences in cost between a
      pair of medical interventions to the differences in the corresponding health
      effects. These research methods are particularly important to neurological
      diseases with debilitating natural histories, long-term courses, and a growing
      number of exciting, yet costly, treatment options available. The results of
      economic evaluations of neurological conditions influence resource allocation
      decisions, help set reimbursement rates, estimate future healthcare expenses, and
      improve the quality and efficiency of delivering neurological care. For these
      research methods to achieve their potential, continued methodological advances
      within the field are needed, as well as a more systematic integration of these
      methods into mainstream research to address critical questions regarding the
      health and well-being of patients with neurological illness.

PMID- 15717038
TI  - Policy-relevant research: when does it matter?
AB  - Evidence-based medicine is most meaningful to policy makers when research
      questions are clearly informed by strategic health policy questions. In
      Washington State workers' compensation, key structural characteristics allow for
      the conduct of effective policy-relevant research. These include clear authority
      and a stable funding stream, a formal relationship between a policy agency and a
      University, development of appropriate research capacity, development of research
      questions related to strategic goals, and a robust data source. The research
      conducted relies on computerized medical bills and work disability records,
      medical records, structured telephone surveys to collect data on pain, functional
      status, quality of life, and computerized data on employment status. The types of
      policy-relevant research include identification of factors leading to preventable
      disability, outcomes research of specific procedures, technology assessment, and
      "real-time" research that addresses rapidly emerging questions. Health policy
      changes implemented from research have been substantial in Washington State
      workers' compensation, including: 1) noncoverage or partial coverage decisions
      for emerging technologies not proven to be of value to injured workers, 2) formal
      treatment guidelines and utilization review criteria for invasive, expensive, or
      marginally effective procedures, 3) disability prevention efforts, and 4)
      relatively rapid changes in policy as emerging patterns suggest harmful outcomes
      from existing treatments (e.g., schedule II opioids). Key structural
      characteristics must be in place to conduct policy-relevant research effectively.
      The workers' compensation system in Washington State is a single-payer system
      with other unique properties that have allowed the emergence of these structural
      characteristics and the conduct of research linked to the strategic goals of
      policy makers.

PMID- 15717039
TI  - Evidence from clinical trials: can we do better?
AB  - Randomized clinical trials provide the most internally valid evidence for medical
      decision-making. In many areas of neurology, results from clinical trials showing
      which therapies are and are not effective have had a substantial impact on
      patient care. Relative to observational methods, the central advantage of
      clinical trials is control of bias attributable to unmeasured differences between
      patients. However, trials also have clear limitations, including a historical
      failure to include a representative cross-section of patients with a given
      disease, and highly structured treatment regimes that are difficult to replicate
      in normal practice settings. These limitations tend to reduce the
      generalizability of results from clinical trials. This article reviews some ways
      in which the design and application of clinical trials could be improved so that
      the evidence produced would be more relevant to health-care providers and other
      decision makers.

PMID- 15717040
TI  - Evidence-based ethics for neurology and psychiatry research.
AB  - American bioethics, historically arising out of theology and philosophy, has been
      dominated by the method of normative analysis. Ethics as policy, however,
      requires in addition a solid evidence base. This paper discusses the background
      conditions that make neurotherapeutics research particularly challenging. Three
      key ethical issues are discussed within an evidence-based ethics framework: the
      ethical challenges arising from changes in the financial incentive structures for
      academic researchers and their institutions, the challenges of risk-benefit
      analysis for neurotherapeutics protocols testing innovative interventions, and
      the evolving issues surrounding impaired decision-making capacity and surrogate
      consent for research. For each of these issues, selected empirical data are
      reviewed, areas for further inquiry are noted, and the need for development of
      novel methods for bioethics policy research is discussed.

PMID- 15717041
TI  - Cell replacement therapy: helping the brain to repair itself.

PMID- 15717042
TI  - Cell therapy in Parkinson's disease.
AB  - The clinical studies with intrastriatal transplants of fetal mesencephalic tissue
      in Parkinson's disease (PD) patients have provided proof-of-principle for the
      cell replacement strategy in this disorder. The grafted dopaminergic neurons can
      reinnervate the denervated striatum, restore regulated dopamine (DA) release and
      movement-related frontal cortical activation, and give rise to significant
      symptomatic relief. In the most successful cases, patients have been able to
      withdraw L-dopa treatment after transplantation and resume an independent life.
      However, there are currently several problems linked to the use of fetal tissue:
      1) lack of sufficient amounts of tissue for transplantation in a large number of
      patients, 2) variability of functional outcome with some patients showing major
      improvement and others modest if any clinical benefit, and 3) occurrence of
      troublesome dyskinesias in a significant proportion of patients after
      transplantation. Thus, neural transplantation is still at an experimental stage
      in PD. For the development of a clinically useful cell therapy, we need to define
      better criteria for patient selection and how graft placement should be optimized
      in each patient. We also need to explore in more detail the importance for
      functional outcome of the dissection and cellular composition of the graft tissue
      as well as of immunological mechanisms. Strategies to prevent the development of
      dyskinesias after grafting have to be developed. Finally, we need to generate
      large numbers of viable DA neurons in preparations that are standardized and
      quality controlled. The stem cell technology may provide a virtually unlimited
      source of DA neurons, but several scientific issues need to be addressed before
      stem cell-based therapies can be tested in PD patients.

PMID- 15717043
TI  - Cell therapy in Huntington's disease.
AB  - Huntington's disease is an autosomal dominant genetic disease, which results in
      progressive neuronal degeneration in the neostriatum and neocortex, and
      associated functional impairments in motor, cognitive, and psychiatric domains.
      Although the genetic mutation is identified, involving an abnormal CAG expansion
      within the htt gene on chromosome 4, the mechanism by which this leads to
      neuronal cell death and the question of why striatal neurones are targeted both
      remain unknown. Thus, in addition to the search for molecular and genetic
      strategies to inhibit development of the disease, we still need to identify
      effective strategies for cellular repair in affected individuals. Aspects of the
      human neuropathology can be well modeled by excitotoxic or metabolic lesions in
      experimental animals, and in transgenic mice carrying the htt mutation, providing
      the basis for testing alternative therapeutic strategies. The rationale and
      efficacy of alternative cell therapies are reviewed, including transplantation
      repair with embryonic striatal tissues, expansion and differentiation of striatal
      like cells from stem cells, and in vivo and ex vivo gene therapy for delivery of
      neuroprotective growth factor molecules. Pilot and experimental clinical trials
      of several approaches are now also underway, and the alternative strategies are
      compared.

PMID- 15717044
TI  - Cell therapy for stroke.
AB  - Increasing experimental evidence suggests that cell transplantation can enhance
      recovery from stroke in animal models of focal cerebral ischemia. Clinical trials
      have been investigating the effects of a human immortalized neuronal cell line
      and porcine fetal neurons in stroke victims with persistent and stable deficits.
      Preclinical studies are focusing on the effects of human stem cells from various
      sources including brain, bone marrow, umbilical cord, and adipose tissue. This
      review presents an overview of preclinical and clinical studies on cell therapy
      for stroke. We emphasize the current, limited knowledge about the biology of
      implant sources and discuss special conditions in stroke that will impact the
      potential success of neurotransplantation in clinical trials.

PMID- 15717045
TI  - Cell therapy in demyelinating diseases.
AB  - Multiple sclerosis presents particular and serious problems to those attempting
      to develop cell-based therapies: the occurrence of innumerable lesions scattered
      throughout the CNS, axon loss, astrocytosis, and a continuing inflammatory
      process, to name but a few. Nevertheless, the limited and relatively focused
      nature of damage to oligodendrocytes and myelin, at least in early disease, the
      large body of available knowledge concerning the biology of oligodendrocytes, and
      the success of experimental myelin repair, have allowed cautious optimism that
      therapies may be possible. Here, we review the clinical and biological problems
      presented by multiple sclerosis in the context of cell therapies, and the
      neuroscientific background to the development of strategies for myelin repair. We
      attempt to highlight those areas where difficulties have yet to be resolved and
      draw on a variety of more recent experimental findings to speculate on how
      remyelinating therapies are likely to develop in the foreseeable future.

PMID- 15717048
TI  - Immune problems in central nervous system cell therapy.
AB  - Transplantation of cells and tissues to the mammalian brain and CNS has revived
      the interest in the immunological status of brain and its response to grafted
      tissue. The previously held view that the brain was an absolute "immunologically
      privileged site" allowing indefinite survival without rejection of grafts of
      cells has proven to be wrong. Thus, the brain should be regarded as a site where
      immune responses can occur, albeit in a modified form, and under certain
      circumstances these are as vigorous as those seen in other peripheral sites.
      Clinical cell transplant trials have now been performed in Parkinson's disease,
      Huntington's disease, demyelinating diseases, retinal disorders, stroke,
      epilepsy, and even deafness, and normally are designed as cell replacement
      strategies, although implantation of genetically modified cells for
      supplementation of growth factors has also been tried. In addition, some
      disorders of the CNS for which cell therapies are being considered have an
      immunological basis, such as multiple sclerosis, which further complicates the
      situation. Embryonic neural tissue allografted into the CNS of animals and
      patients with neurodegenerative conditions survives, makes and receives synapses,
      and ameliorates behavioral deficits. The use of aborted human tissue is
      logistically and ethically complicated, which has lead to the search for
      alternative sources of cells, including xenogeneic tissue, genetically modified
      cells, and stem cells, all of which can and will induce some level of immune
      reaction. We review some of the immunological factors involved in transplantation
      of cells to CNS.

PMID- 15717049
TI  - Positron emission tomography imaging of transplant function.
AB  - In this article, the role of functional imaging for providing objective evidence
      that grafts of fetal tissue can survive and form connections in Parkinson's and
      Huntington's disease patients is reviewed. The dissociation between dopamine
      storage capacity, clinical improvement, and normalization of brain metabolism in
      PD is discussed, and possible mechanisms underlying the phenomenon of dyskinesias
      off medication are presented. It is concluded the positron emission tomography
      and single photon emission computed tomography can provide valuable ancillary
      information alongside clinical observations but are not currently appropriate
      modalities for use as surrogate endpoints.

PMID- 15717051
TI  - Advocacy groups are crucial players in developing new neurotherapeutics.

PMID- 15717050
TI  - The design of clinical trials for cell transplantation into the central nervous
      system.

PMID- 15717046
TI  - Cellular transplantation strategies for spinal cord injury and translational
      neurobiology.
AB  - Basic science advances in spinal cord injury and regeneration research have led
      to a variety of novel experimental therapeutics designed to promote functionally
      effective axonal regrowth and sprouting. Among these interventions are cell-based
      approaches involving transplantation of neural and non-neural tissue elements
      that have potential for restoring damaged neural pathways or reconstructing
      intraspinal synaptic circuitries by either regeneration or neuronal/glial
      replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve
      tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells,
      myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord
      tissue) have already been translated to the clinical arena, whereas others have
      imminent likelihood of bench-to-bedside application. Although this progress has
      generated considerable enthusiasm about treating what once was thought to be a
      totally incurable condition, there are many issues to be considered relative to
      treatment safety and efficacy. The following review reflects on different
      experimental applications of intraspinal transplantation with consideration of
      the underlying pathological, pathophysiological, functional, and neuroplastic
      responses to spinal trauma that such treatments may target along with related
      issues of procedural and biological safety. The discussion then moves to an
      overview of ongoing and completed clinical trials to date. The pros and cons of
      these endeavors are considered, as well as what has been learned from them.
      Attention is primarily directed at preclinical animal modeling and the importance
      of patterning clinical trials, as much as possible, according to laboratory
      experiences.

PMID- 15717047
TI  - The repair of complex neuronal circuitry by transplanted and endogenous
      precursors.
AB  - During the past three decades, research exploring potential neuronal replacement
      therapies has focused on replacing lost neurons by transplanting cells or
      grafting tissue into diseased regions of the brain. However, in the last decade,
      the development of novel approaches has resulted in an explosion of new research
      showing that neurogenesis, the birth of new neurons, normally occurs in two
      limited and specific regions of the adult mammalian brain, and that there are
      significant numbers of multipotent neural precursors in many parts of the adult
      mammalian brain. Recent advances in our understanding of related events of neural
      development and plasticity, including the role of radial glia in developmental
      neurogenesis, and the ability of endogenous precursors present in the adult brain
      to be induced to produce neurons and partially repopulate brain regions affected
      by neurodegenerative processes, have led to fundamental changes in the views
      about how the brain develops, as well as to approaches by which transplanted or
      endogenous precursors might be used to repair the adult brain. For example,
      recruitment of new neurons can be induced in a region-specific, layer-specific,
      and neuronal type-specific manner, and, in some cases, newly recruited neurons
      can form long-distance connections to appropriate targets. Elucidation of the
      relevant molecular controls may both allow control over transplanted precursor
      cells and potentially allow for the development of neuronal replacement therapies
      for neurodegenerative disease and other CNS injuries that might not require
      transplantation of exogenous cells.

PMID- 15717052
TI  - The blood-brain barrier and neurotherapeutics.

PMID- 15717053
TI  - The blood-brain barrier: bottleneck in brain drug development.
AB  - The blood-brain barrier (BBB) is formed by the brain capillary endothelium and
      excludes from the brain approximately 100% of large-molecule neurotherapeutics
      and more than 98% of all small-molecule drugs. Despite the importance of the BBB
      to the neurotherapeutics mission, the BBB receives insufficient attention in
      either academic neuroscience or industry programs. The combination of so little
      effort in developing solutions to the BBB problem, and the minimal BBB transport
      of the majority of all potential CNS drugs, leads predictably to the present
      situation in neurotherapeutics, which is that there are few effective treatments
      for the majority of CNS disorders. This situation can be reversed by an
      accelerated effort to develop a knowledge base in the fundamental transport
      properties of the BBB, and the molecular and cellular biology of the brain
      capillary endothelium. This provides the platform for CNS drug delivery programs,
      which should be developed in parallel with traditional CNS drug discovery efforts
      in the molecular neurosciences.

PMID- 15717054
TI  - How to measure drug transport across the blood-brain barrier.
AB  - The extent to which a substance in the circulation gains access to the CNS needs
      to be determined for potential neuropharmaceuticals as well as for drug
      candidates with primary targets in the periphery. Characteristics of the in vivo
      methods, ranging from classical pharmacokinetic techniques (intravenous
      administration and tissue sampling) over brain perfusions to microdialysis and
      imaging techniques, are highlighted. In vivo measurements remain unmatched with
      respect to sensitivity and for the characterization of carrier-mediated uptake,
      receptor-mediated transport, and active efflux. Isolated microvessels are
      valuable tools for molecular characterization of transporters. Endothelial cell
      culture models of the blood-brain barrier (BBB) are pursued as in vitro systems
      suitable for screening procedures. Recent applications of conditionally
      immortalized cell lines indicate that a particular weakness of culture models
      because of downregulation of BBB-specific transporter systems can be overcome. In
      silico approaches are being developed with the goal of predicting brain uptake
      from molecular structure at early stages of drug development. Currently, the
      predictive capability is limited to passive, diffusional uptake and predominantly
      relies on few molecular descriptors related to lipophilicity, hydrogen bonding
      capacity, charge, and molecular weight. A caveat with most present strategies is
      their reliance on surrogates of BBB transport, like CNS activity/inactivity or
      brain-to-blood partitioning rather than actual BBB permeability data.

PMID- 15717055
TI  - Localization of brain endothelial luminal and abluminal transporters with
      immunogold electron microscopy.
AB  - Immunogold electron microscopy has identified a variety of blood-brain barrier
      (BBB) proteins with transporter and regulatory functions. For example, isoforms
      of the glucose transporter, protein kinase C (PKC), and caveolin-1 are BBB
      specific. Isoform 1 of the facilitative glucose transporter family (GLUT1) is
      expressed solely in endothelial (and pericyte) domains, and approximately 75% of
      the protein is membrane-localized in humans. Evidence is presented for a water
      cotransport function of BBB GLUT1. A shift in transporter polarity characterized
      by increased luminal membrane GLUT1 is seen when BBB glucose transport is
      upregulated; but a greater abluminal membrane density is seen in the human BBB
      when GLUT1 is downregulated. PKC colocalizes with GLUT1 within these endothelial
      domains during up- and downregulation, suggesting that a PKC-mediated mechanism
      regulates human BBB glucose transporter expression. Occludin and claudin-5 (like
      other tight-junctional proteins) exhibit a restricted distribution, and are
      expressed solely within interendothelial clefts of the BBB. GFAP (glial
      fibrillary acidic protein) is uniformly expressed throughout the foot-processes
      and the entire astrocyte. But the microvascular-facing membranes of the glial
      processes that contact the basal laminae are also polarized, and their
      transporters may also redistribute within the astrocyte. Monocarboxylic acid
      transporter and water channel (Aquaporin-4) expression are enriched at the glial
      foot-process, and both undergo physiological modulation. We suggest that as
      transcytosis and efflux mechanisms generate interest as potential
      neurotherapeutic targets, electron microscopic confirmation of their site
      specific expression patterns will continue to support the CNS drug discovery
      process.

PMID- 15717056
TI  - Development of neuropeptide drugs that cross the blood-brain barrier.
AB  - In recent years, there have been several important advancements in the
      development of neuropeptide therapeutics. Nevertheless, the targeting of peptide
      drugs to the CNS remains a formidable obstacle. Delivery of peptide drugs is
      limited by their poor bioavailability to the brain due to low metabolic
      stability, high clearance by the liver, and the presence of the blood brain
      barrier (BBB). Multiple strategies have been devised in an attempt to improve
      peptide drug delivery to the brain, with variable results. In this review, we
      discuss several of the strategies that have been used to improve both
      bioavailability and BBB transport, with an emphasis on antibody based vector
      delivery, useful for large peptides/small proteins, and glycosylation, useful for
      small peptides. Further development of these delivery methods may finally enable
      peptide drugs to be useful for the treatment of neurological disease states.

PMID- 15717057
TI  - Small molecular drug transfer across the blood-brain barrier via carrier-mediated
      transport systems.
AB  - Because of the physiological nature of the blood-brain barrier (BBB), transport
      of chemical compounds between blood and brain has been widely believed to occur
      by means of passive diffusion, depending upon the lipophilicity of the compounds.
      However, discrepancies exist between the lipophilicity and apparent BBB
      permeation properties in many cases, and these discrepancies can be ascribed to
      the existence of multiple mechanisms of drug transport through the BBB. Molecular
      identification and functional analysis of influx transport proteins (from blood
      to brain) and efflux transport proteins (from brain to blood) have progressed
      rapidly. Therefore, the BBB is now considered to be a dynamic interface that
      controls the influx and efflux of a wide variety of substances, including
      endogenous nutrients and exogenous compounds such as drugs, to maintain a
      favorable environment for the CNS. This review focuses on the role of transport
      systems in the uptake of xenobiotics, including organic anionic/cationic and
      neutral drugs, across the BBB into the brain, as well as on strategies to
      increase drug delivery into the brain by blocking efflux transport protein
      function, or to reduce CNS side effects by modulating BBB transport processes.

PMID- 15717058
TI  - Brain-to-blood transporters for endogenous substrates and xenobiotics at the
      blood-brain barrier: an overview of biology and methodology.
AB  - In the past decade, research into P-glycoprotein involving the blood-brain
      barrier (BBB) has seen a shift in the concept of the BBB as a structural barrier
      to that of a functional barrier for xenobiotics and changed simultaneously the
      strategy for the discovery and development of drugs acting in the CNS. As far as
      making advances in neurotherapeutics are concerned, the brain-to-blood transport
      function at the BBB will be one of the most important issues. Knowing the
      limitations of the in vivo and in vitro methods for BBB efflux research, it is
      essential to adopt a multidisciplinary approach in investigating the true
      physiological role of the BBB. Among several methods, the Brain Efflux Index
      method and the use of conditionally immortalized brain capillary endothelial cell
      lines, established from transgenic rats harboring temperature-sensitive simian
      virus 40 large T-antigen gene, are likely to be very useful tools for the BBB
      efflux transport research. According to our recent findings using these methods,
      several transporters in the brain capillary endothelial cells appear to play an
      important role in reducing the brain level of hydrophilic endogenous substrates
      produced either in the brain or peripheral organs, e.g., neurotransmitters,
      neuromodulators, metabolites of neurotransmitters, and uremic toxins. It has been
      reported also that large hydrophilic molecules, such as IgG, apo-transferrin, and
      amyloid-beta peptide, are susceptible to brain-to-blood efflux transport. In the
      light of the latest findings, we have formed the hypothesis that the BBB acts as
      a CNS detoxifying system for both endogenous substrates and xenobiotics in the
      brain. A fuller understanding of the physiological role of BBB efflux
      transporters will provide rational insights to assist in the development of safer
      neurotherapeutics.

PMID- 15717059
TI  - Active efflux across the blood-brain barrier: role of the solute carrier family.
AB  - The brain uptake of xenobiotics is restricted by the blood-brain brain barrier
      formed by brain capillary endothelial cells. Active efflux transport systems in
      the blood-brain barrier work as a detoxification system in the brain by
      facilitating removal of xenobiotic compounds from the brain. Drugs, acting in the
      brain, have to overcome such efflux mechanisms to achieve clinically significant
      concentration in the brain. Multiple transporters are involved in this efflux
      transport in the brain capillaries. In the past few years, considerable progress
      has been made in the cloning of these transporters and their functional
      characterization after heterologous expression. Members of the solute carrier
      family (SLC) play an important role in the efflux transport, especially for
      organic anions, which include organic anion transporting polypeptides (OATP/SLCO)
      and organic anion transporters (OAT/SLC22A). It is believed that coordination of
      the members of SLC family, and ABC transporters, such as P-glycoprotein,
      multidrug resistance protein, and breast cancer-resistant protein (BCRP/ABCG2),
      allows an efficient vectorial transport across the endothelial cells to remove
      xenobiotics from the brain. In this review, we shall summarize our current
      knowledge about their localization, molecular and functional characteristics, and
      substrate and inhibitor specificity.

PMID- 15717061
TI  - Drug transport to brain with targeted liposomes.
AB  - Antibody-conjugated liposomes or immunoliposomes are particulate drug carriers
      that can be used to direct encapsulated drug molecules to diseased tissues or
      organs. The present review discusses examples of successful applications of this
      technology to achieve drug transport across the blood-brain barrier. In addition,
      information will be provided on practical aspects such as phospholipid
      compositions of liposomes, antibody coupling technologies, large-scale production
      of liposomes, and obstacles related to drug loading of the carrier. Prospects of
      future uses of immunoliposome-based drug delivery systems such as gene therapy of
      the brain and clinical trials are discussed.

PMID- 15717060
TI  - Blood-brain barrier active efflux transporters: ATP-binding cassette gene family.
AB  - The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the
      brain from potentially harmful endogenous and exogenous substances. BBB active
      drug efflux transporters of the ATP-binding cassette (ABC) gene family are
      increasingly recognized as important determinants of drug distribution to, and
      elimination from, the CNS. The ABC efflux transporter P-glycoprotein (Pgp) has
      been demonstrated as a key element of the BBB that can actively transport a huge
      variety of lipophilic drugs out of the brain capillary endothelial cells that
      form the BBB. In addition to Pgp, other ABC efflux transporters such as members
      of the multidrug resistance protein (MRP) family and breast cancer resistance
      protein (BCRP) seem to contribute to BBB function. Consequences of ABC efflux
      transporters in the BBB include minimizing or avoiding neurotoxic adverse effects
      of drugs that otherwise would penetrate into the brain. However, ABC efflux
      transporters may also limit the central distribution of drugs that are beneficial
      to treat CNS diseases. Furthermore, neurological disorders such as epilepsy may
      be associated with overexpression of ABC efflux transporters at the BBB,
      resulting in pharmacoresistance to therapeutic medication. Therefore, modulation
      of ABC efflux transporters at the BBB forms a novel strategy to enhance the
      penetration of drugs into the brain and may yield new therapeutic options for
      drug-resistant CNS diseases.

PMID- 15717063
TI  - Neuroprotection in experimental stroke with targeted neurotrophins.
AB  - More than 30 neurotrophins have been identified, and many of them have
      neuroprotective effects in brain ischemia or injury. However, all the clinical
      trials with several neurotrophins for the treatment of acute ischemic stroke or
      neurodegenerative diseases have failed so far, primarily because of their poor
      blood-brain barrier (BBB) permeability. This article is an overview of recent
      progress in the research focused on BBB targeted neurotrophins using a chimeric
      peptide approach, in which antitransferrin receptor antibody was used as a BBB
      delivery vector, and neurotrophin peptide was conjugated to the antibody via the
      avidin/biotin technology. Vasoactive intestinal peptide was the first model
      chimeric peptide to show an enhanced CNS effect after noninvasive peripheral
      administration. Brain-derived neurotrophic factor (BDNF) chimeric peptide was
      neuroprotective in rats subjected to transient forebrain ischemia, permanent
      focal ischemia, or transient focal ischemia. Delayed treatments with the BDNF
      chimeric peptide showed an effective time window of 1-2 h after ischemia. Basic
      FGF chimeric peptide was highly effective in the reduction of infarct volume in
      the rat model of permanent focal ischemia, with lowest effective dose of 1 mug
      per rat. Future studies in this exciting area include genetically engineered
      fusion proteins or humanized antibodies for BBB drug targeting with less
      immunogenicity and reduced working burden in the chemical conjugation, the use of
      antihuman insulin receptor antibody for higher BBB delivery efficiency, and
      combination therapies using chimeric neurotrophins plus other neuroprotectants to
      achieve additive or synergistic effects.

PMID- 15717062
TI  - Drug transport to brain with targeted nanoparticles.
AB  - Nanoparticle drug carriers consist of solid biodegradable particles in size
      ranging from 10 to 1000 nm (50-300 nm generally). They cannot freely diffuse
      through the blood-brain barrier (BBB) and require receptor-mediated transport
      through brain capillary endothelium to deliver their content into the brain
      parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can
      deliver drugs to the brain by a still debated mechanism. Despite interesting
      results these nanoparticles have limitations, discussed in this review, that may
      preclude, or at least limit, their potential clinical applications. Long
      circulating nanoparticles made of methoxypoly(ethylene glycol)- polylactide or
      poly(lactide-co-glycolide) (mPEG-PLA/PLGA) have a good safety profiles and
      provide drug-sustained release. The availability of functionalized PEG-PLA
      permits to prepare target-specific nanoparticles by conjugation of cell surface
      ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain
      targeted pegylated immunonanoparticles can now be synthesized that should make
      possible the delivery of entrapped actives into the brain parenchyma without
      inducing BBB permeability alteration. This review presents their general
      properties (structure, loading capacity, pharmacokinetics) and currently
      available methods for immunonanoparticle preparation.

PMID- 15717064
TI  - Tyrosine hydroxylase replacement in experimental Parkinson's disease with
      transvascular gene therapy.
AB  - Transvascular gene therapy of Parkinson's disease (PD) is a new approach to the
      gene therapy of PD and involves the global distribution of a therapeutic gene to
      brain after an intravenous administration and transport across the blood-brain
      barrier (BBB). This is enabled with the development of a nonviral gene transfer
      technology that encapsulates plasmid DNA inside pegylated immunoliposomes or
      PILs. An 85- to 100-nm liposome carries the DNA inside the nanocontainer, and the
      liposome surface is conjugated with several thousand strands of 2000-Da
      polyethyleneglycol (PEG). This PEGylation of the liposome stabilizes the
      structure in the blood stream. The liposome is targeted across the BBB via
      attachment to the tips of 1-2% of the PEG strands of a receptor-specific
      monoclonal antibody (mAb) directed at a BBB receptor, such as the insulin
      receptor or transferrin receptor (TfR). Owing to the expression of the insulin
      receptor or the TfR on both the BBB and the neuronal plasma membrane, the PIL is
      able to reach the neuronal nuclear compartment from the circulation. Brain
      specific expression is possible with the combined use of the PIL gene transfer
      technology and brain-specific gene promoters. In the 6-hydroxydopamine rat model
      of experimental PD, striatal tyrosine hydroxylase (TH) activity is completely
      normalized after an intravenous administration of TfRmAb-targeted PILs carrying a
      TH expression plasmid. A treatment for PD may be possible with dual gene therapy
      that seeks both to replace striatal TH gene expression with TH gene therapy, and
      to halt or reverse neurodegeneration of the nigro-striatal tract with
      neurotrophin gene therapy.

PMID- 15717067
TI  - The internationalization of scientific production: a great challenge for
      Brazilian nursing.

PMID- 15717068
TI  - [Financial investment in human resources: an experience at a hospital].
AB  - This study aimed to investigate the financial amount a large school hospital
      invested in training programs. Seven training programs for the hospital staff
      were analyzed by means of the absorption costing system, totaling 307 training
      sessions in 1999. Data analysis showed that, during that year, a total of R$
      225,493.84 was invested, that is, R$ 27.41 per worker. There are no data on other
      Brazilian hospitals to compare this figure. However, if this is compared with the
      annual worldwide average of US$ 252 per capita, the mean value is 9.2 times less
      than world average. This figure corresponds to 0.32% of the payment roll, while
      the world average is 2.7%. This study points towards the importance for Permanent
      Education Centers to understand the costs of training programs as well as for
      hospital organizations to create a formal policy for investment in these
      programs.

PMID- 15717066
TI  - Blood-brain barrier genomics, proteomics, and new transporter discovery.
AB  - The blood-brain barrier (BBB) is an impermeable cellular interface that
      physically separates the blood from the interstices of the brain. The endothelial
      cells lining the brain blood vessels form the principle barrier, and their unique
      phenotype is a consequence of dynamic interactions with several perivascular cell
      types present in the brain parenchyma. In addition, BBB dysfunction has been
      observed in the large majority of neurological diseases, but the causes of
      aberrant vascular behavior are generally unknown. Because of its barrier
      phenotype, drug delivery to the brain has also proven to be a very difficult
      task. Global genomics and proteomics analyses are currently being used to examine
      BBB function in healthy and diseased brain to better characterize this dynamic
      interface. It is becoming increasingly evident that these approaches have the
      potential to clarify the unique attributes of a healthy BBB, to identify
      therapeutic targets in diseased brain, and to identify novel conduits for
      noninvasive delivery of drugs against these targets. This review will discuss the
      application of genomics and proteomics to blood-brain barrier research and will
      offer views on the prospects of such approaches.

PMID- 15717065
TI  - RNA interference and nonviral targeted gene therapy of experimental brain cancer.
AB  - The human epidermal growth factor receptor (EGFR) plays an oncogenic role in
      solid cancer, including brain primary and metastatic cancers. Transvascular
      nonviral gene therapy in combination with EGFR-RNA interference (RNAi) represents
      a new therapeutic approach to silencing oncogenic genes in solid cancers. This is
      achieved with pegylated immunoliposomes (PIL) carrying short hairpin RNA
      expression plasmids driven by the U6 RNA polymerase promoter and directed to
      target EGFR expression by RNAi. The PIL is comprised of a mixture of known lipids
      containing polyethyleneglycol (PEG), which stabilizes the PIL structure in vivo
      in circulation. The tissue target specificity of PILs is given by conjugation of
      approximately 1% of the PEG residues to monoclonal antibodies (mAbs) that bind to
      specific endogenous receptors (i.e., insulin and transferrin receptors) located
      in the brain vascular endothelium, which forms the blood brain barrier (BBB), and
      brain cellular membranes, respectively. These mAbs are known to induce 1)
      receptor-mediated transcytosis of the PIL complex through the BBB and 2)
      transport to the brain cell nuclear compartment. Treatment of an experimental
      human brain tumor model in scid mice is possible with weekly intravenous RNAi
      gene therapy causing reduced tumor expression of EGFR and 88% increase in
      survival time of these mice with advanced intracranial brain cancer. The
      availability of additional RNAi tumor targets may improve the therapeutic
      efficacy of this new anticancer drug. The accessibility to chimeric and/or
      humanized mAbs directed to human BBB and brain cell specific-receptors may
      accelerate the application of this technology to the treatment of human tumors.

PMID- 15717069
TI  - [The practice of nursing auxiliaries in the family health program].
AB  - This study aims to evaluate the practice of nursing auxiliaries in the Family
      Health Program, identifying their daily activities, as well as factors that
      facilitate or hinder their work. A qualitative approach was chosen, using the
      focal group technique, with the participation of 34 nursing auxiliaries from the
      Federal District, Brazil. It was found that the nursing auxiliaries carry out a
      variety of activities, both of individual and collective nature, heavily
      influenced by the clinical model and with different degrees of complexity, such
      as: family registration, brief clinical evaluation, group activities, technical
      procedures, home visits, sanitary and epidemiological vigilance in day care
      centers. The participants related that they found it easy to bond with the
      clientele, but complained of the shortage of continuing education courses and
      imprecision as to their true assignments and lack of local coordination. The
      authors conclude that the program must reassess the role of this professional,
      reemphasizing his educational function in the community.

PMID- 15717070
TI  - [Home care: the experience of a private hospital in the state of Sao Paulo].
AB  - Home care is defined as a group of hospital procedures that can be developed at
      home, encompassing health actions developed by a multiprofessional team. This
      study aims at disseminating the experience of a home care service offered by Sao
      Francisco Hospital, located in the city of Ribeirao Preto, presenting the results
      of a 12-month period (from September 2001 to August 2002). During the analyzed
      period, the service provided care mainly to women (57%), with age between 70 and
      80 years (30%), with diagnosis of neurological diseases (27%) and tumors (17%).
      The sector is coordinated by nurses, who are also responsible for bringing in
      clients. The work is performed by an interprofessional team that performs
      procedures of collecting material for lab examinations, dressing, deliver care
      with catheters and ostomies, as well as home hospitalization.

PMID- 15717071
TI  - [Leisure for mothers of high-risk babies: analysis of the experience in these
      women's perspective].
AB  - In view of the implementation of new care strategies for mothers of high-risk
      babies attended at neonatal units through a program involving play, recreation
      and educational activities, this study aims to analyze this experience according
      to these women's perspectives. A qualitative and descriptive study was conducted
      at the University Hospital of Ribeirao Preto, Brazil. Seven mothers were
      interviewed who had attended at least three activity sessions in the program and
      signed an informed consent document. The interviews were taped and were guided by
      the following question: "Tell us about your experience in these group meetings".
      It was observed that the mothers described the activities as "...they are nice
      and help to establish ties" and "...they are good because we get some
      distraction", thus revitalizing them to cope with the stress from long
      hospitalization. They pointed out the opportunity to learn about some types of
      care for their children through games and educational films -- "They solve many
      of our doubts, especially for those who have pre-term babies", as well as the
      opportunity to do manual work -- "We learned how to embroider, which was
      something no one knew how to do". This activity resulted in the production of
      clothing for the child. It was concluded that the program contributed to the
      process of constructing a more integral and humanized care by focusing on the
      family and broadening the perspective on hospitals as places that also offer
      leisure.

PMID- 15717072
TI  - [The environment as a health surveillance issue: analysis of nursing activities].
AB  - The fact that the need for environmental conservation has been on the national
      and international agenda determined the development of this study, which aims to
      examine how the environment is an issue for nurses working in health surveillance
      services, according to their testimonies. From July to August 1999, eight female
      nurses described their routine. Their reports were studied by means of the
      discourse analysis technique. It was concluded that, in general, their actions
      were not aimed at environmental conservation and were limited to factual and
      emergency issues.

PMID- 15717073
TI  - [Profile of adolescents with repeated pregnancies attended at a prenatal clinic].
AB  - This study identified the biopsychosocial profile of adolescent with repeated
      pregnancies, who were attended at a prenatal clinic. Data were collected through
      patient records and interviews and were subject to quantitative analysis. Based
      on the obtained results and in accordance with literature, factors that are
      strongly associated with the occurrence of pregnancy repetition were selected in
      the adolescents' profiles. These are: early menarche; first sexual intercourse
      shortly after menarche; school repetition; school dropout; non remunerated
      occupation; low family income; involvement with older partners; living with the
      partner; consensual union with the partner; one partner; low condom use; family
      history of adolescent pregnancy; father's absence because of death or
      abandonment; positive family reaction to previous pregnancy; previous abortion;
      adolescent's positive concepts about previous delivery; and absence from previous
      postpartum consultations.

PMID- 15717074
TI  - [Acute myocardial infarction and the break with everyday life: possibility of
      preventive nursing action].
AB  - This proposal for Nursing action to prevent acute myocardial infarction (AMI)
      draws on a doctoral thesis research carried out to investigate the experience of
      comfort and discomfort in the patient's perspective, by means of the Symbolic
      Interactionism approach and the Grounded Theory methodology. Data collected by
      means of interviews with 13 men who had suffered AMI, at two hospitals in Sao
      Paulo, Brazil, allowed us to point out what they define as comfortable or
      uncomfortable. This article focuses on the first phase of these men's experience,
      when the main discomfort is the break with everyday life, brought about by the
      onset of symptoms or by the stroke itself, and discusses possibilities for
      Nursing action in primary and secondary AMI prevention.

PMID- 15717075
TI  - [Monitoring and evaluation of side effects of chemotherapy in patients with colon
      cancer].
AB  - This study aimed to monitor and evaluate the occurrence and intensity level of
      nausea, vomiting and diarrhea in patients with colon cancer, submitted to
      outpatient chemotherapy, who received nursing information for handling these
      symptoms. Study participants were 17 patients, who were treated with 5
      Fluorouracil and low doses of folinic acid, at the Adult Outpatient Chemotherapy
      Clinic of the Hospital Sao Paulo/Federal University of Sao Paulo, Brazil.
      Instruments were elaborated for registering these symptoms' occurrence and
      intensity level and a patient guide for handling them. The information and
      patient monitoring were carried out by the nurse during the consultations. The
      results showed that most of the patients (82.4%) displayed at least one of the
      signs and symptoms under study between the first and the 21st day of the
      treatment cycle. Nausea was the most frequent symptom (76.5%), with a peak on the
      4th and 5th day of the cycle, followed by diarrhea (70.5%), with a peak on the
      7th day, and vomiting (53.0%), with a peak on the 5th day. Regarding the
      intensity of these symptoms, most patients were classified as level 1, which was
      established as acceptable for this study. These results indicate that the nursing
      instructions and the continuous monitoring contributed to the effectiveness of
      the patient's symptom management.

PMID- 15717076
TI  - [Nursing at the sterilized material center--continuing education practice].
AB  - This research aims to characterize Continuing Education (CE) practices offered to
      the staff involved in nursing activities at Sterilized Material Centers of
      hospitals located in the micro-region of Sao Jose dos Campos, Brazil. A
      descriptive research with quantitative analysis was carried out through
      structured interviews, with nurses, nursing technicians and auxiliaries,
      sterilization assistants and nursing students. It was found that 31.2% of the
      interviewees (one nurse and nineteen employees) took part in CE; 65.4% of the
      employees were not motivated to participate. The CE is theoretic-practical and
      optional, with direct supervision; employees are evaluated through performance
      observation and analysis, without any other formal instruments. We also observed
      the need for an actual CE service of CE with structured programs.

PMID- 15717077
TI  - [Comparison between the psychophysical scale methods for magnitude estimation and
      category estimation of nurses' social perception].
AB  - This experiment aimed to rank nurses' social perception through the magnitude and
      category estimation methods. Study participants were high school and university
      students, active and retired professionals in the areas of medicine, psychology,
      nursing and dentistry. The results showed: (1) the characteristics neat,
      responsible, clean, careful and efficacious occupied the first positions in terms
      of nurses' social perception; whereas the characteristics useless, dishonorable,
      irresponsible and hateful occupied the last positions in the scales obtained by
      the two direct psychophysical methods, and (2) the non-metric social perception
      continuum has prosthetic characteristics.

PMID- 15717078
TI  - [General aspects and number of phases of the medication system in four brazilian
      hospitals].
AB  - This study identified and analyzed the medication systems in 04 university
      hospitals located in Recife, Ribeirao Preto, Goiania and Sao Paulo, Brazil, after
      approval by the Research Ethics Committee and authorization by the hospital
      directors. Data were collected through a structured interview with one of the
      professionals in charge of the medication system and non-participant and direct
      observation during one week. The results indicated the points requiring
      improvement, such as the use of abbreviations, lack of standardization in
      medication administration times, lack of updated and complete information about
      the patient, the pharmacy's not working 24 hours a day in hospitals and others.
      66 phases were shown in Hospital A, 58 in B, 70 in C, and 80 in D concerning the
      medication system. Simplifying the processes by reducing the number of phases is
      the key to reducing medication errors.

PMID- 15717079
TI  - [Nurses' attitude towards revealing the prognosis of no treatment possibility: a
      matter of bioethics].
AB  - This study aims to get to know nurses' attitude and participation when they have
      to inform a patient about a prognosis of no treatment possibility. Twenty-five
      nurse practitioners from a general public school hospital took part in this
      study. Data were collected through interviews and were analyzed quantitatively
      and qualitatively, showing the following results: 40% of the nurses did not take
      a stand when informing about a prognosis of no treatment possibility; 56% did not
      take any part in the decision of informing the patient about the prognosis of no
      treatment possibility. This disclosed the need for nurses to consider bioethical
      matters, which can be of help in the analysis of dilemmas.

PMID- 15717080
TI  - [Trying to regain control: preschool boys' experience in the post-operative stage
      of circumcision].
AB  - This study was carried out with 3 to 6 year-old boys undergoing circumcision,
      with a view to understanding the meaning of the interactions they experienced
      them during the post-operative period as well as identifying their strategies
      while experiencing the surgery. Symbolic Interactionism was used as a theoretical
      reference framework, and Grounded Theory as a methodological framework. Due to
      these children's verbal development characteristics, the interview was mediated
      by therapeutic play. Their mothers were also interviewed as informers of their
      children's experience. Data were analyzed up to the point of categorization of
      the meanings, revealing the following category of concepts: Trying to regain
      control. Understanding the whole experience offers important elements to rethink
      nursing care to preschool boy who undergo circumcision, as well as to his family.

PMID- 15717081
TI  - [Caring, researching and teaching: meanings and implications of nursing
      practice].
AB  - This article aims to discuss the problem of caring, researching and teaching in
      hospital nursing: general characteristics of Modern Nursing -- teaching and
      practice paradigm; characteristics of the Nightingale System. The research
      methodology was based on the analysis of fundamental care, research and teaching
      concepts in nursing practice, involving technical and gnoseological implications
      for pedagogical and research practice, which are illustrated through examples of
      hospital research. These entail repercussions for an epistemology of nursing. We
      highlight professional attitudes for the state of the art. The author evokes the
      need for disclosure, for efficient research methods and result reliability in
      (oncology?) nursing care, research and teaching activities. The conclusion points
      towards the relevance of nursing as a social practice and the problem of nursing
      activities in any area of care pragmatics -- whether in or outside the hospital
      context.

PMID- 15717082
TI  - Developing global leaders through doctoral education.
AB  - Nursing leadership has become a major theme of discussions in many countries. The
      phenomenon is also present in nursing as the profession is redesigning and
      reinventing itself in all domains of practice. This paper discusses the
      development of global nursing leaders through doctoral education in the context
      of 21st century realities. Next, two meanings of global leadership of nursing are
      reviewed. Finally, doctoral education is focused by looking at worldviews and the
      challenges ahead in preparing global nursing leaders for the 21st century.

PMID- 15717083
TI  - [Education for the XXI century and the reflexive teacher's formation in nursing].
AB  - This study shows expert approaches to education in the last few years and
      discusses the premises of reflexive teaching in this new century. Emphasizing the
      area of professional nursing, we discuss tendencies in the formation, activities
      and development of teachers with respect to the required knowledge and abilities,
      the teaching practice and aspects of nursing teacher's reflexive education in
      Brazil. Besides providing a deeper knowledge about the subject, the literature
      review allowed us to reveal the urgent need to revitalize college teaching from a
      reflexive perspective, in order to increase teachers' commitment and competency
      for professional performance.

PMID- 15717084
TI  - [Research committee of the University of Sao Paulo at Ribeirao Preto College of
      Nursing: objectives and performance (1989-2003)].
AB  - This paper translates the fourteen-year history of the Research Committee of the
      College of Nursing at Ribeirao Preto-USP. It shows the tasks, competencies and
      activities accomplished by their members, emphasizing the Institutional
      Scientific Initiation Program by the National Council for Scientific and
      Technological Development and the University of Sao Paulo, the International
      Scientific Initiation Symposium by the University of Sao Paulo, the research
      groups and the research grant resource modalities under the Committee's
      responsibility or monitoring, highlighting its growing importance in the College
      of Nursing at Ribeirao Preto-USP.

PMID- 15717085
TI  - [Regulatory standard 32 and its implications for nursing workers].
AB  - Workers in health care institutions often face inappropriate work situations
      without considering them as dangerous, however, even if scientific evidence
      demonstrates the presence of various occupational risk agents in work
      environments. This text aimed to present Regulatory Standard (RS) 32, about
      Safety and Health at Work in Health Care Institutions. This RS is important in
      the Brazilian scenario, due to the absence of federal legislation about work
      safety and health issues in the health sector and due to the fact that existing
      regulations are dispersed and joined with other RS and resolutions, which were
      not developed specifically for this purpose. It is concluded that the
      implantation of this RS may result in beneficial changes, since protection
      procedures and measures will have to be taken, promoting safety at work and
      occupational accident prevention among health workers.

PMID- 15717086
TI  - [The influence of the parasitemia on the evolution of the chronic Chagas'
      disease].
AB  - During 13 years, 190 individuals with chagasic infection were submitted to
      clinical and parasitological examinations to investigate the relationship between
      parasitemia and the evolution of chronic chagasic infection. Fifty-six patients
      with positive xenodiagnosis and 134 with negative exams were compared from 1988
      to 91, it was found that 22 (39.3%) and 50 (37.3%), respectively, presented
      disease progression. The parasitemia was stratified into high, medium and low and
      the relation with the disease evolution showed that 5 (62.5%), 10 (41.7%) and 57
      (36.1%), respectively, presented progressive disease, though without a
      statistically significant difference (p>0.05). When 20 patients with persistent
      parasitemia in 1976/91, were compared with 59 with negative xenodiagnosis, a
      progressive evolution was observed in 6 (30%) and 17 (28.8%), respectively.
      Comparing six patients with high parasitemia and 59 with negative exams, it was
      verified that 3 (50%) and 17 (28.8%), respectively, showed progressive disease,
      but this was not statistically significant, (p>0.05). Mean age with high, medium
      and low parasitemia were 39.6, 45.3 and 41.5 years, respectively, (p>0.05). Mean
      age in patients showing progressive, unaltered and regressive evolution was 46.4,
      39.8 and 32.6 years, respectively, with a statistically significant difference
      between progressive and regressive evolution (p<0.05). It is suggested that high
      parasitemia did not have an influence on the evolution of the chronic infection.

PMID- 15717088
TI  - [Pulmonary histoplasmoma in Rio Grande do Sul].
AB  - A retrospective analysis of sixteen patients with pulmonary nodules diagnosed as
      histoplasmoma by histopathologic evidence of Histoplasma capsulatum var
      capsulatum was done in an endemic area for histoplasmosis. Brazilian literature
      was reviewed. All patients were white, nine were men, mean age at diagnosis was
      50.8 years. Six (37.5%) patients had a relevant epidemiologic story. The
      pulmonary nodules were 0.7-2.7 cm in diameter, presenting as granulomatous
      lesions with caseous necrosis. Twelve (75%) patients had solitary nodules.
      Histoplasmoma as a rule is a solitary nodule of up to 3 cm in an asymptomatic
      patient. The diagnosis is made from histopathologic evidence of the fungus, which
      is accomplished using a special fungus stain, Gomori-Grocott methenamine silver.
      Cultures or seromycology do not help the diagnosis.

PMID- 15717087
TI  - [Respiratory syncytial virus -- associated lower respiratory tract infections in
      hospitalized infants].
AB  - For analysis of clinical features and outcome of hospitalized infants with
      respiratory syncytial virus lower respiratory tract infection, was carried out.
      Cross-sectional study with 89 infants, hospitalized in two public hospitals
      during the 1997 and 1998 RSV seasons, in Rio de Janeiro city. Nasopharyngeal
      secretions were obtained and specimens processed for viral antigens detection by
      indirect immunofluorescence assay with the use of anti RSV, anti-influenza A and
      B and anti parainfluenza type 3 monoclonal antibodies. Patients were allocated
      into three diagnostic groups: bronchiolitis or wheeze bronchitis (n = 44);
      Pneumonia (n = 26) and bronchiolitis or wheeze bronchitis and pneumonia (n = 19).
      Positivity for RSV was found in 42 (47.1%) patients. More days of hospitalization
      were seen in 1997 in comparison with the follow year (p >0.05). No clinical
      differences were found between RSV positive and negative children. The
      sensitivity and specificity for wheezing concerning the isolation of RSV were,
      respectively, 85% and 65%. RSV was the major cause of LRTI in hospitalized
      infants.

PMID- 15717089
TI  - [Clinical and epidemiological characteristics of snakebites in Rio Branco, Acre].
AB  - This study aimed to determine the clinical epidemiological profile of the snake
      bites attended at the reference hospital of Acre. One hundred-forty four patients
      were studied prospectively, from January to December 2002. One hundred-thirteen
      (78.5%) cases were classified as accidents by venomous snakes. The genera
      Bothrops, Lachesis and Micrurus were responsible, respectively, for 75.7%, 2.1% e
      0.7% cases. The accidents predominated in males (78.5%), rural workers (51.4%)
      and between 10 and 29 years old (43.8%). The distribution according to the
      severity of poisoning by genera Bothrops was: moderate (48.6%), mild (31.2%) or
      severe (20.2%). Two cases of Bothrops accident did not receive serum therapy.
      However, the antivenom was administered in twenty-three patients without
      envenoming. In conclusion, the results obtained were different of the observed by
      another authors with respect to the severity of accidents and suitable treatment.

PMID- 15717090
TI  - [American cutaneous leishmaniasis: phlebotomine transmission area in the
      Municipality of Uberlandia, MG].
AB  - From May 2000 to January 2001 four, 15 hour-long collections of phlebotomine were
      done to the insect monitoring. The collection was done in an area of infection of
      American cutaneous leishmaniasis in the basin of the Araguari River in the
      municipality of Uberlandia (MG). The first collection was made in May (a cold,
      damp month), the second in June 2000 (a cold, dry month) the third in October
      2000 (a hot, dry month) and the fourth in January 2001 (a hot, rainy month). CDC
      and Shannon light traps were used 6551 phlebotomne were captured and identified,
      1990 male and 4562 female, comprised of two lines (Lutzomyia and Brumptomyia) and
      8 species. Lutzomyia intermedia predominated with the largest number of specimens
      (6531), which accounted for 99.7% of the collected insects. In the four
      collections, it was observed that Lutzomyia intermedia manifested a preference
      for the month preceding the rainy season, with its high temperatures and
      humidity.

PMID- 15717091
TI  - [Proteic profile and antigenic recognition of extracts from Wuchereria bancrofti
      L3 infective larvae].
AB  - A study of protein characterization and recognition of the antigenic profile was
      accomplished in extracts of infective larvae (L3) from Wuchereria bancrofti. Two
      proteins of relative molecular weight of 49 and 55 kDa were recognized as
      antigenic in all extracts by the tested sera. The secretory/excretory antigen
      presented the largest number of recognized bands (105, 100, 76, 55, 49, 39 and 32
      kDa) followed by the somatic antigen (100, 76, 55 and 49 kDa) when incubated with
      pools of sera from healthy individuals resident in endemic areas (normal
      endemics). Human sera and parasitized blood used to infect mosquitoes in order to
      obtain L3, were collected from microfilaraemic individuals living in a filariasis
      endemic area. From 792 persons screened with the thick smear technique, 87 (11%)
      were positive. No statistical significance was observed between genders. The
      group between 11 and 19 years of age presented higher percentage of infection
      (36.8%).

PMID- 15717092
TI  - Comparative clinical and ultrasound study of egg-negative and egg-positive
      individuals from Schistosoma mansoni low morbidity endemic areas, and
      hospitalized patients with hepatosplenic disease.
AB  - Two hundred and twenty three subjects from a Schistosoma mansoni low morbidity
      endemic area and nine hospitalized hepatosplenic patients were submitted to stool
      test and clinical examination and abdomen ultrasound assessments. According to
      stool examination and ultrasound results, they were grouped as follows: G1 -- 63
      Schistosoma mansoni egg-negative individuals; G2 -- 141 egg-positive patients and
      without evidence of periportal fibrosis; G3 -- 19 egg-positive patients with
      periportal echogenicity (3-6 mm); and G4 -- 9 hepatosplenic patients with
      periportal echogenicity (> 6 mm). Hepatomegaly detected by physical examination
      of the abdomen evaluated in the midclavicular line was verified in G1, G2 and G3,
      respectively, in 11.1, 12.1 and 26.3%. In G1, G2 and G3, periportal thickening
      occurred only in schistosomal patients (8.5%). Mild pathological alterations in
      patients that cannot yet be detected by clinical examination were detectable in
      the liver by ultrasound and can be due to fibrosis. The degree of mild periportal
      fibrosis was diminished in 57.9% of patients 12 months after treatment of
      schistosomiasis with oxamniquine. At ultrasonography, the mean liver left lobe
      measurement of G3 was larger than that of G1, and that of G4 larger than that of
      G1 and G2. The mean size of the spleen of G4 was significantly larger than that
      of the other three groups, and that of G3 larger than that of G1 and G2.

PMID- 15717093
TI  - [Evaluation of the effect of splenectomy with autologous spleen tissue
      implantation in some monocyte functions in children with hepatosplenic
      schistosomiasis mansoni].
AB  - Adherence index, superoxide and TNF-alpha production in monocytes, with or
      without tuftsin treatment, were investigated in hepatosplenic schistosomiasis
      mansoni bearers with splenectomy with or without autologous implantation of
      spleen tissue. Three groups were evaluated: Healthy volunteers control group (CG)
      (n=12); Splenectomy with seft auto-transplant AG (n=18) and Splenectomy without
      auto-transplant WAG (n=9). Adherence index and TNF-alpha did not differ among the
      groups. Superoxide production was similar in CG and AG, in the 1st hour after
      cell stimulation. SP was larger in each hour time in CG and AG groups as compared
      WAS group. TT recovered normal pattern of SP in AG comparable with levels found
      in CG, with increase from the 1st to 2nd hour. However, TT did not alter SP in
      WAG, which remained reduced in all time points. Autologous implantation of spleen
      tissue seems to contribute for recovery and maintenance of the evaluated
      immunological reactions, which might be important in response to infections.

PMID- 15717094
TI  - [Dermatologic lesions in patients infected with the human T-cell lymphotropic
      virus type 1 (HTLV-1)].
AB  - Human T-cell Lymphotropic virus type I (HTLV-1) was the first human retrovirus
      described. Some time after its discovery a group of diseases were related to this
      virus, such as, adult T-cell leukemia lymphoma (ATLL), HTLV-1 associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 associated uveitis
      (HAU). In the nineties, HTLV-1 was associated to a severe eczema of children,
      called infective dermatitis (ID). Since then, several other skin manifestations
      have been observed in HTLV-1-infected individuals, particularly in patients with
      ATLL or HAM/TSP. However, according to some reports, dermatologic lesions are
      also common in asymptomatic HTLV-1 carriers. Besides ID, all other skin lesions
      reported are nonspecific. The aim of this review is to outline the dermatologic
      manifestations reported in HTLV-1 infected patients, emphasizing the clinical and
      epidemiological value of these findings.

PMID- 15717095
TI  - Chagas' disease: study of congenital transmission in cases of acute maternal
      infection.
AB  - We studied three pregnant women with acute chagasic infection. Two patients,
      infected in the third trimester of pregnancy, had uninfected children. The third
      patient, infected earlier, had an infected newborn. These results encourage
      research on risk factors of transmission and on medical decisions concerning
      pregnant women with acute Chagas' disease.

PMID- 15717097
TI  - [First description of an autopsied case of melioidosis in Ceara State].
AB  - An autopsied case is reported concerning fulminant sepsis with predominantly
      pulmonary lesions, caused by Burkholderia pseudomallei, etiologic agent of
      melioidosis, originating from interior of Ceara State, Northeastern Brazil where
      there had been no previous cases reported. Autopsy findings and differential
      diagnosis are discussed.

PMID- 15717096
TI  - Intestinal spirochetosis and colon diverticulosis.
AB  - A case of intestinal spirochetosis in a 62-year-old white male is reported. The
      condition was characterized by chronic flatulence and episodes of intestinal
      hemorrhage, in addition to the evidence of hypotonic diverticular disease, with a
      large number of slender organisms in the colon epithelium and cryptae.
      Spirochetes were demonstrated by Whartin-Starry stain. The serologic tests for
      syphilis and HIV were positive. Spirochetosis was treated with penicillin G, and
      the patient remains free of intestinal complaints 20 months later.

PMID- 15717098
TI  - [Erythema nodoso in reactivation of Chagas' disease after cardiac
      transplantation].
AB  - We report a patient with Chagas' disease that presented Trypanosoma cruzi
      reactivation after cardiac transplantation and immunodepression, characterized by
      skin lesions of erythema nodosum. This is an unusual presentation of Chagas'
      disease.

PMID- 15717099
TI  - [Effect of larvae density on adult size of Aedes aegypti reared under laboratory
      condictions].
AB  - To evaluate the influence of larval density in development of Aedes aegypti
      mosquitoes we evaluated three different densities. It was observed that
      conditions of high larval density and shortage of food produced a reduction in
      the size of adults and increased mortality rate of Aedes aegypti in laboratory
      conditions.

PMID- 15717100
TI  - [Determination of antistreptolysin "O" and C-reactive protein among school
      children of Laranjal, PR].
AB  - For antistreptolysin "O" and C-reactive protein determination, carried out in
      Laranjal-PR, we analyzed the serum of 411 school children aged from 5 to 16. For
      antistreptolysin O, 13.6% had elevated titers and 5.1% were reactive for C
      reactive protein. No differences related to age or sex were observed.

PMID- 15717101
TI  - [Prevalence of intestinal parasitosis in the city of Eirunepe, Amazon].
AB  - Samples of 413 patient were analyzed and positivity was found in 64.4% (266) of
      the exams. The intestinal parasites most prevalent were: Ascaris lumbricoides
      (35.6%); Trichuris trichiura (18.6%); Ancylostomides (9.9%); Strongyloides
      stercoralis (1%), Enterobius vermiculares (0,5%); Entamoeba histolytica (13.3%)
      and Giardia lamblia (1%). The presence of varied degrees of anemia were detected
      in 39.8% of the exams.

PMID- 15717102
TI  - [HP: an improved model of suction light trap for the capture of small insects].
AB  - This paper describes a new model of light trap, named HP, based on the widely
      used CDC trap. Its advantages include high efficiency, easy handling and
      transport. Moreover, it is almost totally made of national materials, which
      reduces considerably the final cost.

PMID- 15717103
TI  - [Occurrence of protozoa and helminthes in faecal samples of stray dogs from
      Itapema City, Santa Catarina].
AB  - Samples of feces from dogs seized by the health surveillance program of Itapema
      city, SC, were studied. From 158 samples examined 121 (76.6%) were positive, with
      a prevalence of Ancylostoma spp (70.9%), followed by Toxocara canis (14.5%),
      Trichuris vulpis (13.9%), Isospora spp (6.3%) and Dipylidium caninum (1.9%).

PMID- 15717104
TI  - Preliminary evidence of association between species of mosquitoes in Atlantic
      forest of Santa Catarina State, (Diptera: Culicidae).
AB  - A positive coefficient of association (affinity) between Runchomyia reversa and
      Anopheles cruzii and high (0.38) index were observed, probably due to the similar
      breeding places (bromeliads) and to landing habits. Furthermore, a high (0.92)
      index of association between Oc. scapularis and Wyeomyia incaudata, with low
      coefficient of association was observed.

PMID- 15717105
TI  - [Research on antibodies anti toxoplasma gondii in intraocular fluids (Aqueous and
      vitreous humor) from patients with ocular toxoplasmosis, in the City of Belem,
      Para State].
AB  - Tests were performed for antibodies IgG, IgM and IgA anti-Toxoplasma gondii
      antibodies in serum and intraocular fluids (Aqueous and vitreous humor) from
      patients with ocular toxoplasmosis. By the results obtained, it was verified that
      intraocular IgG and IgA anti-Toxoplasma gondii antibodies can be important
      markers for the diagnosis of ocular toxoplasmosis.

PMID- 15717106
TI  - Colonic polyps in hepatosplenic schistosomiasis mansoni.

PMID- 15717107
TI  - [International Meeting on Surveillance and Prevention of the Chagas Disease in
      the Amazonia: implementation of the Inter-government Initiative Surveillance and
      Prevention of the Chagas Disease in the Amazonia. Manaus, State of Amazon,
      Brazil, 19-22 of September of 2004].

PMID- 15717108
TI  - [Spinal fibrocartilaginous embolism].
AB  - Fibrocartilaginous embolism (FCE) of the spinal cord is a rare cause of ischemic
      myelopathy. We describe a 13-year-old patient with probable post-traumatic FCE.
      History of disease, clinical presentation, diagnostic workup, and disease course
      are outlined. Diagnosing FCE in the living often seems to be merely conjectural.
      Therefore, vertebral edema adjacent to the level of the spinal lesion is a
      possibly valuable diagnostic hint of spinal ischemia. Furthermore, exclusion of
      systemic embolism and other etiologies of myelopathy is necessary to corroborate
      the diagnosis of FCE. The postulated pathomechanism, diagnostic procedures,
      therapy, and prognosis of FCE are discussed in this article.

PMID- 15717109
TI  - [Intelligence, attention, and memory in patients with myasthenia gravis].
AB  - BACKGROUND: In patients with myasthenia gravis (MG), poor performance on
      cognitive tests has been found. Performance on memory tasks has been reported to
      correlate with disease activity, but memory in MG patients was also recently
      found to be unimpaired. PATIENTS AND METHODS: Cognitive functioning was examined
      in 23 patients with MG and 23 healthy controls. The patients were assessed for
      IQ, memory, attention, and motor performance. Immunoglobulin G antiacetylcholine
      receptor autoantibody titers were determined. Event-related potentials were
      generated for patients and controls. RESULTS: Mean IQs of patients were at
      average. Memory and attention were not more impaired in patients than controls.
      Event-related potentials were not delayed in either group. Patients with elevated
      autoantibody concentrations similarly showed unimpaired neurocognitive and motor
      functioning. CONCLUSION: In this study, no evidence of neuropsychological
      impairment was found in MG, arguing against the involvement of higher cortical
      functions. Sleep abnormalities rather than central mechanisms may explain the
      memory impairments reported by some studies.

PMID- 15717110
TI  - [Psychotherapeutic intervention for disturbed emotional regulation in complex
      post-traumatic stress disorder].
AB  - Pervasive disturbances in emotional regulation are a frequent problem for
      patients with complex trauma disorders. Emotional instability is a core
      diagnostic criterion of borderline personality disorder, in which a high
      prevalence of physical and sexual childhood abuse has been found. Self-injury,
      substance abuse, and binge-eating are strategies for coping with unbearable
      traumatic emotions. Therapeutic strategies for improving emotion regulation
      include pharmacological and psychological approaches. For the former, serotonin
      reuptake inhibitors have been shown to improve emotion regulation. The latter,
      psychotherapeutic techniques are: refocusing attention on positive emotions,
      imaginative distancing, resource activation, cognitive methods for improving
      affect differentiation, and fostering confidence in relationships and emotional
      attachment through the experience of a positive therapeutic relationship.

PMID- 15717112
TI  - [Long-term effects of traumatic experiences on somatic and psychic complaints of
      German World War Two refugees].
AB  - The effects of expulsion from German territories following World War Two have not
      been studied systematically, and little is known about long-term effects of this
      potentially traumatic experience. Via mail, 600 refugees from former German
      territories due to World War Two were asked to complete questionnaires about
      biographic data, somatic and psychic health (SCL-90-R questionnaire), and
      specific aspects related to traumatic experiences (post-traumatic stress disorder
      questionnaire). Of those contacted, 25% participated in the investigation. Of
      them, 9.8% fulfilled diagnostic criteria of post-traumatic stress disorder
      according to DSM IV. Only 1.8% of an age-matched control group met these
      criteria. Analysis of the SCL-90-R questionnaire showed higher scores for former
      refugees in somatic and psychic complaints than the control group. We show that
      expulsion following war may lead to symptoms of post-traumatic stress disorder
      and somatic and psychic complaints after more than 50 years. Our investigation
      supports the necessity of adequate care for subjects expelled from their home
      countries and the psychologically traumatised.

PMID- 15717114
TI  - Autoinfarcted wandering spleen and fatal pneumococcal sepsis in an infant.
AB  - A wandering or ectopic spleen, a rare congenital condition caused by improper
      fixation of the ligamentous attachments, was identified during a postmortem
      examination of a 10-month-old female who had died of Streptococcus pneumoniae
      sepsis. The wandering spleen was autoinfarcted and adherent to the left hepatic
      lobe, with resultant functional hyposplenism.

PMID- 15717113
TI  - ["Home treatment" for mental illness. Concept definition and effectiveness].
AB  - A number of projects have used home treatment (HT) for severely mentally ill
      people in recent years. This paper intends to define HT and show the main
      differences between it and other forms of psychiatric community service, present
      the existing evidence for HT, and discuss eligibility criteria. Studies about
      HT's efficacy in treating severely mentally ill adults were identified by
      electronic (MEDLINE, PsycLIT) and manual search. Six studies met these inclusion
      criteria. Compared to inpatient treatment, HT was equally or more efficacious in
      respect to reduction of symptom distress, social (re-)integration, and patient
      and carer satisfaction. Furthermore, direct costs for HT were often lower than
      for inpatient care. However, the number of relevant studies is limited and
      knowledge on the long-term effects of HT is sparse.

PMID- 15717111
TI  - [Patients with epilepsy and anxiety disorders. Diagnosis and treatment].
AB  - Up to 50-60% of patients with epilepsy may develop psychiatric complications, in
      particular depression, anxiety, and psychotic disorders. Although this
      comorbidity has received a great deal of attention in recent years, the anxiety
      spectrum of psychiatric disturbances in epilepsy patients has not been
      extensively studied, although this comorbidity has a significant effect on the
      medical management and quality of life. The etiology is multifactorial, including
      neurobiological and shared pathophysiological mechanisms as well as psychosocial
      and iatrogenic factors (e.g., influence of antiepileptic drugs, epilepsy
      surgery). Despite the high prevalence of comorbid anxiety in epilepsy, very
      little is known about optimal treatment strategies. This article reviews the
      complex interrelationships between anxiety disorders and epilepsy from a clinical
      point of view. The evaluation of anxiety relative to ictal, peri-ictal, and
      postictal states is described, and medical treatment options for anxiety
      disorders in patients with epilepsy are discussed, illustrating that their
      treatment extends far beyond seizure control.

PMID- 15717115
TI  - Pediatric inflammatory bowel disease.

PMID- 15717116
TI  - Re: Corkscrew-like malformations of umbilical cord.

PMID- 15717117
TI  - A basis for distinguishing cultured dendritic cells and macrophages in cytospins
      and fixed sections.
AB  - There is a burgeoning literature on the contrasting role of intratumoral
      dendritic cells (DCs) and tumor-associated macrophages, making reliable
      identification of both cell types in clinical and experimental tissue sections
      important. However, because these cell types are closely related and share
      several differentiation antigens, their absolute distinction in tissue sections
      is difficult. We differentiated DCs and macrophages from monocytes in vitro,
      prepared cytospins and paraffin-embedded sections of the various cell
      populations, and tested a variety of antibodies that purportedly recognize
      monocytes and DCs for their capacity to react and distinguish cells after
      conventional formalin fixation. Cultured DCs but not macrophages were detected by
      fascin, DC-LAMP, and CD83 with a predictable increase in staining that paralleled
      their maturation. Staining by CD1a was found on immature DCs but was weak and
      absent on mature DCs and macrophages, respectively. CD14 and CD163 were
      characteristic for macrophages and absent on DCs. CD68, HLA-DR, and S100 did not
      discriminate between DCs and macrophages. We conclude that antigens such as HLA
      DR and S100 are not in themselves sufficient for identification of DCs in
      formalin-fixed tissue sections, but that additional macrophage-specific (CD14,
      CD163) and DC-specific (CD1a, CD83, fascin, DC-LAMP) antigens should be used to
      distinguish cell types from each other and to provide information on their state
      of maturation.

PMID- 15717118
TI  - Epstein-Barr virus-associated lymphoproliferative disorder presenting as
      apparently isolated gastrointestinal lesions in childhood.
AB  - We present an unusual case of post-transplant lymphoproliferative disorder (PTLD)
      presenting as apparently isolated gastrointestinal lesions in a pediatric renal
      transplant recipient. The multiple bowel lesions were related to Epstein-Barr
      virus and demonstrated the appearance of a monomorphic PTLD that was
      morphologically indistinguishable from diffuse large B-cell lymphoma. The patient
      responded to therapy with targeted anti-CD20 immunotherapy. PTLD may manifest as
      apparently isolated gastrointestinal tract lesions in childhood.

PMID- 15717119
TI  - Inhibition of VSV and EMCV replication by the interferon-induced GTPase, mGBP-2:
      differential requirement for wild-type GTP binding domain.
AB  - Interferons (IFNs) exert their anti-viral activities through the induction of
      anti-viral proteins. One member of the guanylate binding protein (GBP) family of
      IFN-induced GTPases, hGBP-1, has previously been shown to contribute to the
      antiviral activities of IFNs. Murine GBP-2 inhibited the replication of both
      vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV). A wild
      type GTP binding motif was not required for VSV inhibition but was required for
      inhibition of EMCV. This is the first demonstration of the role of enzymatic
      activity in the antiviral activities of GBPs and these findings suggest different
      mechanisms of inhibition for the two viruses.

PMID- 15717120
TI  - Genetic characterization of H5N1 avian influenza viruses isolated in southern
      China during the 2003-04 avian influenza outbreaks.
AB  - The recent H5N1 avian influenza outbreaks in Asia spread over more than 8
      countries. It has caused enormous economic loss and grand challenges for the
      public health. During these breakouts we isolated three strains of H5N1 Avian
      Influenza Virus (AIV) from chickens and one from duck in different farms of
      Southern China. We completely sequenced these four AIVs. Molecular
      characterization demonstrated that these strains retain the reported H5N1 AIV
      sequence properties relevant to virus virulence and host adaptation. Phylogeny
      results demonstrated that three of these isolates (except
      A/Chicken/Guangdong/174/04) were closely linked to other H5N1 AIVs isolated from
      the recent H5N1 outbreaks in Asia. Six of 8 segments (except PA and M) of
      A/Chicken/Guangdong/174/04 also shares a close linkage to other H5N1 AIVs
      isolated from the recent H5N1 outbreaks. However, the PA gene of
      A/Chicken/Guangdong/174/04 and another H5N1 strain forms a distinct subgroup
      along with an H6N1 AIV, and the M gene of A/Chicken/Guangdong/174/04 shows a
      close linkage to some H5N1 AIVs from aquatic species in China. Our findings
      suggest that a new genotype of AIV (in addition to previous reported ones) was
      present during the 2003-04 Asian bird flu outbreaks and that continuing virus
      surveillance of AIVs be conducted to monitor the evolutionary paths of the
      A/Chicken/Guangdong/174/04-like AIVs.

PMID- 15717121
TI  - Construction and expression of a new fusion protein, thymosin alpha1-cBLyS, E.
      coli.
AB  - A fusion thymosin alpha1-soluble B lymphocyte stimulator (TM alpha1-cBLyS) gene
      was generated to engineer a bifunctional lymphokine, which was then over-produced
      in Escherichia coli. The molecular weight of the expressed fusion protein was
      approximately 28 kDa. After being purified by Ni-NTA affinity column, the fusion
      protein had full activity of BLyS with a slightly higher immunological action
      than synthetic TMalpha1. Because TM alpha1 regulates the cellular immune response
      and cBLyS amplifies the humoral response, this bifunctional lymphokine could be
      useful in the treatment of various immunodeficiency syndromes and serve as an
      immunomodulator to enhance the host's response to vaccination.

PMID- 15717122
TI  - A novel psychrotrophic fungus, Mortierella minutissima, for D-limonene
      biotransformation.
AB  - Of 98 strains of moulds, isolated from arctic soils, Mortierella minutissima 01,
      grew the best on agar plates with limonene vapor. Perillyl alcohol and perillic
      acid were the main products of limonene biotransformation. Maximal yield of
      perillyl alcohol (125 mg l(-1)) occurred in medium containing 0.8% substrate, at
      15 degrees C, pH 6 and after 4-5 d.

PMID- 15717123
TI  - Enhanced nisin production by increasing genes involved in nisin Z biosynthesis in
      Lactococcus lactis subsp. lactis A164.
AB  - Nisin Z production in Lactococcus lactis subsp. lactis A164 was improved by
      introducing multicopy genes, nisZ, nisRK, or nisFEG, involved in nisin
      biosynthesis into A164 strain. A similar growth profile was obtained from all
      strains tested. However, the cells expressing nisRK produced 25,000 AU nisin Z
      ml(-1) compared to 16,000 AU ml(-1) by the control strain. Northern blot analysis
      revealed that over-expression of nisRK promoted the transcription of the nisZ
      gene. The A164 strain expressing multicopy nisFEG also had an increased nisin Z
      production (25,000 AU ml (-1)) but produced the nisin more slowly than the cells
      expressing multicopy nisRK.

PMID- 15717124
TI  - Hydrogenation of C-C double bonds in an ionic liquid reaction system using the
      obligate anaerobe, Sporomusa termitida.
AB  - Sporomusa termitida reduced caffeate (1mM) in anaerobic, two-liquid phase,
      reaction systems containing either tetradecane or 1-butyl-3-methylimidazolium
      hexafluorophosphate [[bmim][PF6]] (20% v/v). The initial rate and final product
      yield were 20 and 7% lower, respectively, in [bmim][PF6]. Since caffeate
      partitioned only into the aqueous phase, the lower rate cannot be attributed to
      mass transfer barriers. Therefore, [bmim][PF6] inhibited the biocatalyst, perhaps
      unsurprisingly since it is very polar and hydrolyses to produce HF.

PMID- 15717125
TI  - High level expression of kringle 5 fragment of plasminogen in Pichia pastoris.
AB  - Angiogensis can be blocked by inhibitors such as endostatin and angiostatin. The
      kringle 5 fragment of plasminogen also has a potent inhibitory effect on
      endothelial cell proliferation and leads to the inhibition of angiogenesis. It
      has promise in anti-angiogenic therapy due to its small size and potent
      inhibitory effect. Preparation of kringle 5 has been achieved through the
      proteolysis of native plasminogen and recombinant DNA technology. Bacterially
      expressed recombinant kringle 5 is mainly insoluble and expressed at low level.
      The refolding yield is also low. To produce recombinant human kringle 5 in a
      large quantity, we have genetically modified a strain of Pichia pastoris. On
      methanol induction, this strain expressed and secreted biologically active,
      recombinant kringle 5. The expression level of the engineered strain in culture
      reached more than 300 mgl(-1). Purification was easily achieved by precipitation,
      hydrophobic and DEAE ion exchange chromatography. The recovery of recombinant
      kringle 5 was about 50% after purification. Yeast-expressed kringle 5 has a
      higher activity in anti-endothelial proliferation than bacterially expressed
      kringle 5.

PMID- 15717126
TI  - Translation enhancement by optimized downstream box sequences in Escherichia coli
      and Mycobacterium smegmatis.
AB  - The effect on translation of downstream box sequences optimized for binding to
      Mycobacterium smegmatis and Escherichia coli 16S rRNA in the absence of a Shine
      Dalgarno (SD) region was investigated. The relative translational efficiency of
      each construct in either M. smegmatis or E. coli was determined. Eradication of
      the SD region in the absence of a downstream box abolished the translation
      activity. In contrast, optimized downstream box constructs resulted in a 13- and
      18-fold increase in protein synthesis, relative to non-optimized DB controls in
      E. coli and M. smegmatis, respectively.

PMID- 15717127
TI  - Head group specificity of phospholipase D isoenzymes from poppy seedlings
      (Papaver somniferum L.).
AB  - The biocatalytical potential of two new phospholipase D (PLD) isoenzymes from
      poppy seedlings (Papaver somniferum L.), PLD-A and PLD-B, was examined by
      comparing their activities in phospholipid transformation. Both enzymes showed
      the same ratio in rates of hydrolysis [phosphatidylcholine
      (PC):phosphatidylglycerol (PG):phosphatidylserine:phosphatidylinositol =
      1:0.5:0.3:0.1] and were inactive towards phosphatidylethanolamine (PE). PLD-A did
      not catalyze head group exchange whereas PLD-B showed a high
      transphosphatidylation potential in the conversion of PC into PG and PE. This
      enzyme also catalyzed the transesterification of octadecylphosphocholine into
      octadecylphosphoglycerol or octadecylphosphoethanolamine.

PMID- 15717128
TI  - Relationship between physical, biochemical and biomechanical properties of tissue
      engineered cartilage-carrier-constructs.
AB  - Three-dimensional cartilage-carrier-constructs were produced according to a
      standard protocol from chondrocytes of an adult mini-pig. Physical parameters
      (height and weight) correlated very well with total DNA content (r2 = 0.86, re.
      0.94). The relation between DNA content and glycosaminoglycan content was less
      but still significant. No significant relationship was found between the
      elasticity module and the DNA content, even if the elasticity module increased
      slightly at higher DNA content. With respect to later implantation, selection of
      a construct for implantation based on the weight, which can be determined non
      invasive and under sterile conditions, seems to be justifiable.

PMID- 15717129
TI  - Effects of N- and C-terminal truncation of HP (2-20) from Helicobacter pylori
      ribosomal protein L1 (RPL1) on its anti-microbial activity.
AB  - HP (2-20) [derived from the N-terminal region of Helicobacter pylori Ribosomal
      Protein L1 (RPL1)], a 19-mer peptide, possesses broad-spectrum anti-microbial
      activity. As the N- (residues 2-3) and C-terminal (residues 14-20) residues can
      be deleted without affecting antimicrobial activity, we have now determined the
      minimum chain length necessary for the retention of antimicrobial activity, and
      its mode of action. The N- (residues 2-3) and C-terminal (residues 17-20)
      truncated fragments [HP (4-16)] induce increased antibiotic activity against
      several bacterial strains without hemolysis. Flow cytometric analysis, scanning
      electron microscopy and fluorescence confocal microscopy revealed that HP (4-16)
      acted rapidly on the plasma membranes of the fungal cells in a salt- and energy
      independent manner.

PMID- 15717130
TI  - Production of an anti-fungal substance for biological control of Phytophthora
      capsici causing phytophthora blight in red-peppers by Streptomyces halstedii.
AB  - The culture broth of Streptomyces halstedii AJ-7 suppressed the growth of
      Phytophthora capsici, which causes phytophthora blight in red-peppers, with less
      than 1% survival of the pathogen after 12 h of treatment. The low molecular
      fraction (< or = 10 kDa) of the culture broth retained anti-fungal activity
      against P. capsici after being held at 100 degrees C for 6 h.

PMID- 15717131
TI  - Mediated electrochemical measurement of the inhibitory effects of furfural and
      acetic acid on Saccharomyces cerevisiae and Candida shehatae.
AB  - The toxic effects of furfural and acetic acid on two yeasts, Saccharomyces
      cerevisiae and Candida shehatae, were evaluated using an electrochemical method.
      Intracellular redox activities were lowered by 40% and 78% for S. cerevisiae and
      C. shehatae, respectively, by 8 g furfural l(-1), and by 46% and 67%,
      respectively, by 8 g acetic acid l(-1). The proposed method can accurately
      measure the effects of inhibitors on cell cultures.

PMID- 15717134
TI  - Prevention of nitrate tolerance with angiotensin II receptor type 1 blocker in
      patients with stable angina: yet another failed strategy to prevent tolerance.

PMID- 15717132
TI  - Novel polyethylene glycol derivative suitable for the preparation of mono
      PEGylated protein.
AB  - A novel methoxypolyethylene glycol (mPEG) derivative, containing a reactive group
      of 1-methyl pyridinium toluene-4-sulfonate, was synthesized and characterized.
      The mPEG derivative was successfully conjugated with two proteins: recombinant
      human granulocyte-colony stimulating factor (rhG-CSF) and consensus interferon (C
      IFN). Homogeneous mono-PEGylated proteins were obtained which were identified by
      high performance size-exclusion chromatography and MALDI-TOF mass spectrometry.
      The biological activities of the mono-PEGylated rhG-CSF and the mono-PEGylated C
      IFN were maintained at 90% and 88%, respectively.

PMID- 15717135
TI  - The statin breakthrough--remembering to involve the patient.

PMID- 15717136
TI  - Comparative effects of rapid bolus administration of aqueous amiodarone versus 10
      minute cordarone I.v. infusion on mean arterial blood pressure in conscious dogs.
AB  - OBJECTIVE: This study was designed to test the hypothesis that rapid bolus
      administration of an aqueous formulation of intravenous amiodarone causes less
      hypotension than a 10-minute infusion of the standard formulation, Cordarone IV.
      Hypotension was the most common adverse event reported with Cordarone IV. The
      hypotension was not dose related, but related to the rate of infusion. Therefore,
      product labeling calls Cordarone and its generic formulations to be administered
      over 10 minutes. Cordarone IV contains polysorbate 80 and benzyl alcohol, each
      causes hypotension. A new aqueous formulation of amiodarone (Amio-Aqueous) does
      not contain these agents and therefore may cause less hypotension. METHODS: Six
      conscious beagle dogs were instrumented with a telemetric device for blood
      pressure monitoring. The study was conducted on 5 days. On the first 2 days, a 10
      min infusion or a bolus of D(5)W was administered (placebo). Over the following 3
      days, the dogs received (in randomized order, one per day) a 10-min infusion of
      2.5 mg/kg Cordarone IV and boluses of 2.5 mg/kg and 5.0 mg/kg Amio-Aqueous
      injected over 2 to 5 sec. The dogs were monitored for 2 hrs after dosing.
      RESULTS: Compared to placebo, boluses of aqueous amiodarone produced no
      significant changes in the mean arterial blood pressure (MABP). In contrast,
      Cordarone infusion produced significant decreases in MABP that lasted for at
      least 2 hrs (p < 0.001). CONCLUSION: Amio-Aqueous had significantly better
      hemodynamic profile permitting rapid intravenous administration. This is a
      significant advantage over the standard formulation, because Cordarone cannot be
      administered by rapid bolus due to excipient-related hypotension.

PMID- 15717137
TI  - Cardioprotective action of perindopril versus candesartan in renovascular
      hypertensive rats.
AB  - We investigated the effects of an angiotensin-converting enzyme inhibitor and an
      angiotensin II type 1 receptor blocker on cardiac hypertrophy in rats with
      renovascular hypertension. Renovascular hypertensive (Goldblatt) rats were
      surgically prepared from Wistar rats. Four weeks later, the rats showed a
      significant increase in blood pressure. At high doses, both the perindopril (1
      mg/kg/day) and the candesartan (2 mg/kg/day) decreased the systolic pressure in
      these rats to the level of control Wistar rats. At low doses (perindopril 0.1
      mg/kg/day and candesartan 0.1 mg/kg/day), these drugs lowered blood pressure to
      85% of that in hypertensive rats. Echocardiographic and morphological studies
      revealed severe cardiac hypertrophy and fibrosis in untreated Goldblatt rats.
      High-dose treatment with both drugs suppressed the progression of hypertrophy and
      fibrosis. Also, low-dose perindopril prevented cardiac hypertrophy and fibrosis.
      In contrast, at the same levels of blood-pressure reduction, low-dose candesartan
      did not prevent cardiac fibrosis nor the upregulation of cardiac collagen types I
      and III mRNA observed in untreated Goldblatt rats. Atrial natriuretic peptide
      mRNA was up-regulated in untreated Goldblatt rats. These changes were
      significantly decreased by both doses of perindopril or the high dose of
      candesartan. Serum levels of angiotensin II and aldosterone were significantly
      higher in untreated Goldblatt rats. Both doses of perindopril inhibited
      activation of the renin-angiotensin system, whereas candesartan had weaker
      effects. In particular, serum aldosterone was 347 +/- 20 pg/ml in low-dose
      perindopril versus 1796 +/- 324 pg/ml in low-dose candesartan. These results
      suggest that there were no differences between the cardioprotective actions of
      perindopril and candesartan at high dosages. On the other hand, low-dose
      treatment with perindopril was more effective in preventing cardiac fibrosis than
      was low-dose treatment with candesartan, despite similar changes in blood
      pressure. It is possible that changes in aldosterone secretion are related to
      this difference.

PMID- 15717138
TI  - Angiotensin II-receptor antagonist losartan does not prevent nitroglycerin
      tolerance in patients with coronary artery disease.
AB  - The study evaluated the effect of Losartan in preventing nitrate tolerance during
      continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary
      disease. Fifteen subjects with chronic stable ischemia evaluated by exercise
      test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval
      plus Losartan 100 mg or Losartan-placebo with a double blind crossover design.
      Myocardial ischemic parameters during stress test were evaluated after each test
      period and results of Losartan therapy were compared to those with placebo. Time
      to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg
      with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or
      Losartan-placebo (p < 0.001). ST-depression at peak exercise and time to recovery
      of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo
      run-in (p < 0.05), sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001) or
      Losartan-placebo (p < 0.05). At 1 mm-ST depression and at peak exercise, systolic
      blood pressure and rate-pressure product significantly decreased after sustained
      TD-GTN 20 mg plus Losartan 100 mg (p < 0.001, p < 0.05 respectively) with respect
      to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo.
      Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg
      compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo (p <
      0.001). The AT(1) antagonist Losartan administration does not prevent the
      development of nitrate tolerance during continuous TD-GTN therapy.

PMID- 15717139
TI  - Intrauterine growth retardation is a risk factor for cisapride-induced QT
      prolongation in preterm infants.
AB  - BACKGROUND: Cisapride is a possible cause of potentially life threatening QT
      prolongation. AIMS: We investigated these cardiac side effects in premature
      infants, mainly in relation to fetal growth. PATIENTS: Forty six preterms (mean
      birth weight 1.350 g, mean post conceptional age 31 weeks) were studied. Thirty
      one of them were appropriate for gestational age (AGA) and 15 were small for
      gestational age (SGA). Cisapride was randomly administered at a 0.3 mg/kg or 0.6
      mg/kg daily dose. Fifty preterms (15 SGA/35 AGA) not treated with Cisapride were
      used as control group. METHODS: A pre-treatment ECG was performed and the QT
      corrected (Bazzet's formula) intervals were compared with the in-treatment values
      (normal values < or =440 mseconds). In the control group two different ECG were
      performed with a timing similar to the treated group (mean interval 5 days).
      RESULTS AND CONCLUSIONS: No patients showed clinical evidence of drug toxicity.
      In the small for gestational age group, both baseline QTc (mean 397; range 370
      420 ms) and in-treatment QTc (mean 410 range 360-500 ms) were significantly
      higher than those found in the appropriate for gestational age group (mean 386,
      range 360-420 ms; mean 396, range 370-420 ms, respectively). This difference was
      found also in the first ECG of the control group. Moreover the mean QTc
      lengthening during treatment was significantly higher in small for gestational
      age group than in the appropriate for gestational age group. Three infants showed
      a rise in the QTc interval above the value of 440 ms and all were SGA (p = 0.03).
      No significant correlation was found between birth weight or gestational age and
      the change in QTc values during Cisapride treatment in the appropriate for
      gestational age group. Intrauterine growth retardation is a major risk factor for
      Cisapride-induced QT prolongation in preterm infants.

PMID- 15717140
TI  - Analysis of the surface electrocardiogram for monitoring and predicting
      antiarrhythmic drug effects in atrial fibrillation.
AB  - Specific antiarrhythmic therapy with class I and III drugs for atrial
      fibrillation (AF) conversion and prevention of its recurrence is frequently
      utilized in clinical practice. Besides being only moderate effective, the
      utilization of antiarrhythmic drugs may be associated with serious side effects.
      In the clinical setting it is difficult to directly evaluate the effects of
      antiarrhythmic drugs on the individual patient's atrial electrophysiology,
      thereby predicting their efficacy in restoring and maintaining sinus rhythm.
      Analysis of the surface electrocardiogram in terms of P-wave signal averaged ECG
      during sinus rhythm and spectral characterization of fibrillatory waves during AF
      for evaluation of atrial antiarrhythmic drug effects is a new field of
      investigation. Both techniques provide reproducible parameters for characterizing
      atrial electrical abnormalities and seem to contain prognostic information
      regarding antiarrhythmic drug efficacy. Further research is needed which
      elucidates the most challenging clinical questions in AF management whom to place
      on antiarrhythmic drug treatment and what antiarrhythmic drug to prescribe.
      Analysis of the surface ECG might have the potential to answer these questions.

PMID- 15717141
TI  - Lipid-lowering therapy in patients with average cholesterol and high
      cardiovascular risk, insights from the Heart Protection Study.
AB  - Although the benefits of cholesterol-lowering with statins has been established
      for patients with high cholesterol levels as well as for patients with prior
      occlusive coronary heart disease, substantial uncertainty has existed about the
      long-term benefits of these agents in particular types of patient, including
      patients with moderate or low baseline cholesterol levels pre-treatment, women,
      the elderly, and those with prior occlusive non-coronary vascular disease. The
      Heart Protection Study was designed to resolve these uncertainties and to provide
      substantially more safety information of statins. In this report the study is
      presented with the significance and practical implications of the results briefly
      discussed.

PMID- 15717142
TI  - Cost-effectiveness of losartan versus atenolol in treating hypertension--an
      analysis of the LIFE study from a Swiss perspective.
AB  - AIMS: To determine the economic benefit of losartan versus atenolol in patients
      with essential hypertension from the perspective of the Swiss healthcare system.
      METHODS AND RESULTS: The cost-effectiveness of losartan versus atenolol in the
      treatment of hypertension was analyzed by applying the results of the LIFE study
      to the Swiss healthcare system using a decision analysis framework. The cost
      effectiveness shows the losartan cohort to provide an additional life expectancy
      of 0.05 years per patient compared to the atenolol cohort, over a mean follow-up
      period of 4.8 years. Losartan therapy in hypertensive patients produced net cost
      savings of CHF 24 per patient and per 4.8 years compared to atenolol from the
      perspective of the Swiss health care system. This result was robust after varying
      costs of medication, stroke, myocardial infarction and life expectancy.
      CONCLUSION: The use of a losartan-based regimen in hypertensive patients with
      left ventricular hypertrophy in Switzerland is net cost-saving compared with a
      atenolol-based regimen.

PMID- 15717143
TI  - Level of awareness of on-treatment patients about prescribed statins.
AB  - BACKGROUND: Statins are frequently prescribed drugs for patients with coronary
      heart disease according to evidence-based medicine. However, compliance with
      these agents has still been far from ideal, since they require long term,
      probably life long therapy. We conducted a survey on patients who were already on
      statin treatment and evaluated their level of awareness of prescribed statins.
      METHODS: 236 participants (117 male, 119 female), who had been on treatment with
      statins for at least three months, were enrolled in our study after giving
      informed consent. Patients were asked close-ended survey questions. RESULTS: Only
      5.5% of participants were on statin treatment for primary prevention, and 16.1%
      of them had a CHD equivalent, defined as those with clinical manifestations of
      noncoronary forms of atherosclerotic disease (peripheral arterial disease,
      abdominal aortic aneurysm, carotid artery disease) and diabetes mellitus. Most
      participants (70%) stated that they had been using statins to decrease
      cholesterol, whereas 16.5% stated that they had no idea. More than half of the
      participants (58%) stated that they did not know how long they would have to keep
      using their statins, whereas 21% replied that they would use them continuously.
      One fifth of participants had some idea about side effects. Participants in whom
      statin therapy was started during hospitalisation for coronary angiography and/or
      PCI more frequently answered that statins should be used continuously (49% vs.
      12% not hospitalised, p < 0.01). Also, therapy adjustment by the physician led to
      a better understanding of the need for continuous use (55% vs. 31% without
      medication change, p < 0.001), as was the case for patients with < 2 co
      medications (36% vs. 17% with > 2 co-medications, p 0.002). Presence of other
      risk factors did not have any impact on level of awareness. CONCLUSION:
      Comprehensive information at initial prescription, initiation of statins during
      hospitalization, dose adjustment during follow up, and as little co-medication as
      possible seem to increase the level of awareness of the benefits of long-term
      statin treatment. This might result in better compliance rates.

PMID- 15717144
TI  - A patient responding to combined therapy with pirmenol and midodrine for
      refractory neurally mediated syncope complicated by prostatic hypertrophy.
AB  - A 67-year-old man with neurally mediated syncope (NMS) complicated by prostatic
      hypertrophy responded well to combined therapy with pirmenol and midodrine. In
      2003, syncope occurred while the patient was driving a car. Results of head-up
      tilt-table testing (HUT) suggested a mixed type of NMS. Oral administration of
      disopyramide provided severe urinary obstruction. Pirmenol treatment was not
      associated with syncope during ordinary HUT, but nausea, sweating, and syncope
      occurred during HUT with provocative administration of isosorbide dinitrate.
      Combined therapy with pirmenol and midodrine avoided syncope during HUT, and has
      prevented attacks since discharge from the hospital.

PMID- 15717145
TI  - Federal guidelines for prophylactic ICD therapy in high risk populations for
      sudden cardiac death: is this a necessary course correction?

PMID- 15717146
TI  - Clinical study regarding the anatomical structures of the right atrial isthmus
      using intra-cardiac echocardiography: implication for catheter ablation of common
      atrial flutter.
AB  - BACKGROUND: The construction of complete bi-directional block in the isthmus
      (ITH) between the tricuspid annulus and inferior vena cava by radiofrequency
      energy (RF) applications is sometimes hampered due to anatomical problems such as
      a thick isthmus or aneurysmal pouch in patients with common atrial flutter (AFL).
      METHODS AND RESULTS: Fifteen patients were referred for RF ablation of AFL. The
      anatomical thickness of the right atrial ITH, diameter of the right atrium and
      thickness of the right atrial free wall were determined using intracardiac
      echocardiography (ICE), along with the endocardial electrogram recordings at the
      ITH. RF was applied at the ITH to create a transmural incision to treat the AFL.
      A significant parallel relationship between the maximum amplitude of the atrial
      electrogram and the thickness of the ITH, was observed. When the maximum
      amplitude of the atrial electrogram at the ITH exceeded 1.5 mV, the thickness at
      the ITH was approximately larger than 5 mm. CONCLUSIONS: Using ICE, the precise
      measurement of the anatomical structures in the heart, including the ITH, was
      feasible. From the amplitude of the atrial electrogram, a deduction of the
      thickness at the ITH was possible, which is indispensable information for the
      appropriate selection of the RF devices.

PMID- 15717147
TI  - The roles of anatomy, image, and electrogram voltage in ablation of cavotricuspid
      isthmus.

PMID- 15717148
TI  - Catheter location, tracking, cardiac chamber geometry creation, and ablation
      using cutaneous patches.
AB  - OBJECTIVE: The ability to construct a three-dimensional (3-D) surface model of
      the endocardium and track the location of catheters within a cardiac chamber,
      using only cutaneous patches, would be a useful advancement in treating
      arrhythmias. We tested the feasibility of such a system, Ensite NavX (Endocardial
      Solutions, Inc., St. Paul, MN, USA), in patients undergoing catheter ablation for
      SVTs. METHODS: Sixteen patients with 20 arrhythmias undergoing ablation were
      selected. Skin electrode patches were placed on the chest to create a 3-D
      coordinate system. A low-amplitude, 5.7 kHz signal emitted from the patches was
      received by conventional catheters positioned in the heart. Catheter location was
      determined by measuring the field strength received by the catheters. Location
      points were successively acquired while catheters were moved throughout the
      chamber. This information was collected and processed by a workstation to create
      a detailed 3-D model of the endocardial surface. Anatomic landmarks were labeled
      on the model as the mapping catheter was navigated. 3-D cardiac chamber geometry
      reconstruction, landmark labeling, and real time catheter tracking were performed
      successfully in all patients. Up to six catheters, with a total of up to 26
      intracardiac electrodes, were tracked simultaneously. RESULTS: Constructed
      geometries, including major vessels and valves, correlated closely with
      traditional anatomic models as well as intracardiac recordings and fluoroscopic
      images. CONCLUSIONS: Real-time catheter tracking and 3-D cardiac chamber model
      construction is feasible using cutaneous patches and conventional catheters. This
      approach may be useful in the treatment of patients with cardiac arrhythmias
      where ablation therapy is primarily anatomically based.

PMID- 15717149
TI  - Computerized three-dimensional potential mapping with a multielectrode basket
      catheter can be useful for pulmonary vein electrical disconnection.
AB  - INTRODUCTION: Pulmonary vein (PV) isolation (PVI) has been recently proposed as
      an effective technique to cure atrial fibrillation (AF). AIMS OF THE STUDY: The
      aim of this study was to investigate the efficacy of a novel technique utilizing
      a computerized three-dimensional mapping system (QMS2) with a multielectrode
      basket catheter (MBC) for PVI and to reveal the relation between the style of
      breakthrough and the network of the PV musculature. METHODS: Sixty-five
      consecutive patients with frequent AF attacks underwent PV mapping with a 31-mm
      MBC, and a three-dimensional color animation of the potential map was constructed
      by the QMS2. The animation color schema was arranged to minimize the low
      amplitude left atrial (LA) potentials and emphasize the high-amplitude PV
      potentials (PVPs). The longitudinal PVP map enabled us to recognize the true
      breakthroughs and reveal the network of the PV musculature. RESULTS: A total of
      205 PVs (65 left superior PVs, 65 right superior PVs, 57 left inferior PVs and 18
      right inferior PVs) were mapped and successful PVI was achieved in all PVs,
      except one that had no PVPs, with a mean radiofrequency duration of 7 +/- 5
      minutes per PV. In about 90% of the PVs, a final radiofrequency application
      eliminated all the distal PVPs simultaneously because the PVI was performed at
      the appropriate LA-PV junction. A single segmental breakthrough was detected in
      17 PVs, single broad breakthrough in 83 PVs, multiple separate breakthroughs with
      a distal connection between the PV musculatures extending from each separate
      breakthrough in 88 PVs and multiple separate breakthroughs without that
      connection in 16 PVs. During the follow-up period, fifty-one (78%) patients were
      free of symptomatic AF without any antiarrhythmic drugs after multiple procedures
      (thirty-three (51%) of those patients after the first procedure) and no PV
      stenosis was found. CONCLUSIONS: Computerized three-dimensional potential mapping
      can be useful for PVI because it can not only identify the true breakthrough, but
      can also confirm the elimination of the breakthroughs by the change in the
      activation sequence through the network of the PV musculature.

PMID- 15717150
TI  - Outcome of ablation for sustained focal atrial tachycardia in patients with and
      without a history of atrial fibrillation.
AB  - OBJECTIVES: The aim of this study was to determine the long-term results of
      ablation for sustained focal atrial tachycardia in patients with and without a
      history of atrial fibrillation. METHODS: A history of atrial fibrillation was
      documented in 25 of 111 patients (23%) with focal atrial tachycardias. We studied
      the results of focal ablation during a follow-up of 27 +/- 22 months. RESULTS:
      Enlargement of left atrium (Odds ratio 2.99) and septal origin of the atrial
      focus (Odds ratio 5.68) were independent predictors of coexisting atrial
      fibrillation. Patients with a septal origin of the focal atrial tachycardia were
      older (62 vs. 54 years) and had a higher rate of structural heart disease than
      patients with a non-septal site of origin (51 vs. 29%). A higher rate of atrial
      fibrillation was found in patients with anteroseptal (56%), midseptal (50%) and
      posteroseptal (36%) atrial tachycardias than in patients with focal atrial
      tachycardias arising from the crista terminalis (9%), the tricuspid (12%) and
      mitral annulus (0%), the ostia of thoracic veins (17%) and other right atrial
      (27%) and left atrial free wall sites (10%). During the follow-up, atrial
      fibrillation was documented in 3% of patients without preexisting atrial
      fibrillation. In patients with focal atrial tachycardia and a history of atrial
      fibrillation, at least one episode of atrial fibrillation was documented during
      follow-up in 64% of patients, but 60% of patients reported marked symptomatic
      improvement. CONCLUSION: An increased rate of coexisting atrial fibrillation was
      found in patients with a septal origin of focal atrial tachycardia. Ablation of
      the focal atrial tachycardia may eliminate both arrhythmias, but patients with a
      history of atrial fibrillation may still be prone to recurrences of atrial
      fibrillation after focal ablation.

PMID- 15717151
TI  - Cryothermal ablation treatment of atrial flutter--experience with a new 9 French
      8 mm tip catheter.
AB  - BACKGROUND: Cardiac cryoablation has been used to successfully treat a variety of
      arrhythmias. OBJECTIVE: This study documents our experience with a new 9 French
      (FR) 8 mm cryocatheter for ablation treatment of symptomatic atrial flutter.
      METHODS: A total of 77 consecutive patients with symptomatic atrial flutter were
      treated. Electrophysiological studies (EPS) were performed with diagnostic
      catheters and ablation was performed with a 9FR, 8 mm tip, quadripolar
      cryocatheter (Freezor MAX catheter, CryoCath Technologies Inc., Kirkland,
      Canada). Cryoablation at -75 degrees C for 8 minutes was performed, beginning at
      the inferior rim of the coronary sinus (CS) os and creating a posterior line to
      the Eustachian ridge. Safety, bidirectional isthmus block at intervention, and
      recurrence at 3 months post procedure were assessed. RESULTS: There were no
      adverse events reported. All patients remained free of discomfort on cryoenergy
      delivery. The acute success rate at intervention was 96% for all patients and
      100% for those with common atrial flutter. Follow-up data from 47 patients showed
      33 (70%) patients without conduction recurrence on repeat EPS at 3 months.
      Although, 1 (2%) patient had both symptom and conduction recurrence. Data
      available from 53 acutely successful patients at 6 month clinical follow-up
      showed that 48 (91%) patients were asymptomatic and 5 (9%) patients had
      recurrence documented by ECG and/or patient diary records. CONCLUSIONS: Our
      experience with a new 9FR, 8 mm tip, quadripolar cryocatheter yielded a high
      success rate at intervention and an excellent safety profile. Although repeat EPS
      at 3 months post ablation identified conduction recurrence in 30% of patients, at
      6 month clinical follow-up only 9% of patients had recurrence. Further monitoring
      is necessary to assess whether the relatively low recurrence rate observed at 6
      month clinical follow-up is maintained over the long term.

PMID- 15717153
TI  - Electroanatomical mapping and radiofrequency catheter ablation of atrial
      tachycardia originating from the recipient heart with recipient-to-donor atrio
      atrial conduction after orthotopic heart transplantation.
AB  - Atrial tachycardias resulting from recipient-to-donor atrio-atrial conduction
      after orthotopic heart transplantation are difficult to treat. We present two
      patients in whom atrial tachycardia originating in the recipient heart were
      successfully treated by radiofrequency ablation guided by electroanatomical CARTO
      mapping system. These cases illustrate that such atrial tachycardia are curable
      by radiofrequency ablation. Electroanatomical CARTO mapping is useful in
      identifying the site of origin of the tachycardia and the atrio-atrial conduction
      sites.

PMID- 15717152
TI  - Paraseptal accessory pathway in Wolff-Parkinson- White-Syndrom: ablation from the
      right, from the left or within the coronary sinus/middle cardiac vein?
AB  - AIMS: In 1999 the consensus statement "living anatomy of the atrioventricular
      junctions" was published. With that new nomenclature the former posteroseptal
      accessory pathway (APs) are termed paraseptal APs. The aim of this study was to
      identify ECG features of manifest APs located in this complex paraseptal space.
      METHODS AND RESULTS: ECG characteristics of all patients who underwent
      radiofrequency ablation of an AP during a 3 year period were analyzed. Of the 239
      patients with one or more APs, 30 patients had a paraseptal AP with
      preexcitation. Compared to APs within the coronary sinus (CS) or the middle
      cardiac vein (MCV) the right sided paraseptal APs significantly more often showed
      an isoelectric delta wave in lead II and/or a negative delta wave in aVR. The
      left sided paraseptal APs presented a negative delta wave in II significantly
      more often compared to the right sided APs. CONCLUSIONS: According to the site of
      radiofrequency ablation, paraseptal APs are classified into 4 subgroups:
      paraseptal right, paraseptal left, inside the CS or inside the MCV. Subtle
      differences in preexcitation patterns of the delta wave as well as of the QRS
      complex exist. However, the definitive localization of APs remains reserved to
      the periinterventional intracardiac electrogram analysis.

PMID- 15717154
TI  - Feasibility of his bundle pacing as an alternative pacing site: measurement of
      his refractoriness.
AB  - BACKGROUND: Direct pacing of the His bundle has been proposed for permanent
      pacing to maintain physiological synchrony of ventricular activation. Measurement
      of His bundle refractoriness may be useful in predicting suitability of this
      technique in an individual. We sought to determine whether this could be measured
      consistently in patients, defining a normal range. METHODS: His bundle pacing was
      performed in 20 consecutive patients (mean age 44.6 +/- 19.5, 5 male) undergoing
      electrophysiology study. Incremental and extrastimulus testing were performed
      from the His region to determine effective and functional refractory periods of
      the His bundle. RESULTS: Consistent His capture was possible in 18 of 20 (90%)
      patients studied. Extrastimulus testing from the His region at a drive cycle
      length of 600 msec was successful in all of these patients. With loss of His
      capture, QRS duration prolonged 32%, and stimulus to atrial electrogram interval
      prolonged 49.6 +/-16.3 msec. The effective refractory periods at drive cycle
      lengths 600, 500, and 400 msec were 407 +/- 70 msec, 320 +/- 39 msec, and 336 +/-
      54 msec, respectively. Corresponding functional refractory periods were 414 +/-
      62, 371 +/- 52, and 329 +/- 32. Consistent capture with incremental His pacing
      was possible in 50% of patients, and 1:1 His capture was lost at mean cycle
      length 408 +/-93 msec. CONCLUSIONS: His refractory periods can be determined
      consistently in unselected individuals undergoing electrophysiological studies.
      Measurement of HERP and HFRP may prove useful in assessing the suitability of the
      His bundle for permanent pacing.

PMID- 15717155
TI  - Pre-procedure duplex ultrasonography to assist cephalic vein isolation in
      pacemaker and defibrillator implantation.
AB  - BACKGROUND: Difficulty in isolating the cephalic vein contributes to failed
      pacemaker and intracardiac cardioverter-defibrillator (ICD) implantation via the
      cephalic venous approach. The deltopectoral groove is used as a rough landmark,
      but the vein is often not found here. We evaluated the benefit of pre-procedural
      duplex ultrasonography in isolating the cephalic vein. METHODS: We enrolled 80
      consecutive patients undergoing new pacemaker or defibrillator implantation and
      performed duplex ultrasonography to localize the cephalic vein before
      implantation. The corresponding surface location in the infraclavicular region
      and the depth of the cephalic vein were identified and recorded if the vein was
      well visualized. Using the imaging results, we dissected the skin over the
      predicted location until the cephalic vein was isolated. We determined the depth
      and corresponding surface location of the proximal cephalic vein during surgery.
      Afterward, we compared localization of the vein using imaging, surgery, and the
      deltopectoral-groove method. The relationship between cephalic vein depth and
      body parameters was also evaluated after the procedure. RESULTS: All proximal
      cephalic veins were successfully isolated under the assistance of pre-procedural
      duplex ultrasonography. When the corresponding surface locations were compared,
      the location depicted on sonograms was closer to the surgical finding than the
      location determined by using the deltopectoral-groove method (0.5 +/- 3.9 vs. 4.9
      +/- 9.6 mm; P < .001). The depth of the cephalic vein derived from duplex
      sonograms showed excellent correlation with the surgical findings (r = 0.93, P <
      0.001). The cephalic vein depth and body mass index (BMI) also showed a linear
      relationship with good correlation (r = 0.70, P < 0.001). CONCLUSION: Pre
      procedural duplex ultrasonography helped in localizing the proximal cephalic vein
      and isolating the cephalic vein. Surface localization of the proximal cephalic
      vein was superior with sonography than with the deltopectoral-groove method.
      There was a linear relationship with good correlation between BMI and cephalic
      vein depth.

PMID- 15717156
TI  - Novel steerable telescoping catheter system for implantation of left ventricular
      pacing leads.
AB  - Advances in left ventricular transvenous lead delivery systems for biventricular
      pacing are leading to more refined techniques, shorter procedure times and higher
      implant success rates. Despite these advances, the inability to successfully
      cannulate the coronary sinus and deliver a lead to a distal location are still
      major causes of prolonged procedures times and implant failures. The
      pathophysiologic process of heart failure results in dilatation of the right
      atrium as well as other morphological changes in cardiac anatomy. Additionally,
      cannulation can be further complicated by congenital anomalous cardiac anatomy.
      This report describes the implant of a biventricular pacing system using a novel,
      steerable 7 French catheter system developed to aid in the cannulation of the
      coronary sinus ostium and its venous branches. The steerable catheter is used in
      conjunction with a 9 French braided sheath and guide-wire to create a telescoping
      system. The use of new tools and methods as described provides insight into
      available options for left ventricular transvenous lead implantation and dealing
      with difficult anatomy.

PMID- 15717157
TI  - Etienne Jules Marey (1830-1904).

PMID- 15717159
TI  - Psychometric testing of the Impact of Event Scale-Chinese Version (IES-C) in oral
      cancer patients in Taiwan.
AB  - GOALS OF WORK: No culturally relevant instrument exists to assess the impact of
      cancer on patients in Taiwan. Therefore, this two-phase study was undertaken to
      (1) develop a Chinese version of the Impact of Event Scale (IES), (2) examine its
      psychometric properties, and (3) use the IES-Chinese version (IES-C) to assess
      the impact of cancer in newly diagnosed oral cancer patients in Taiwan. PATIENTS
      AND METHODS: The psychometric properties of the 15-item IES-C were tested in 106
      newly diagnosed oral cancer patients and analyzed by descriptive statistics, test
      retest reliability, Pearson's correlation, and principal component analysis. MAIN
      RESULTS: The results showed that (1) the IES-C has satisfactory content validity
      and feasibility; (2) overall internal consistency (Cronbach's alpha) was 0.91
      with values of 0.91 and 0.81 for intrusion and avoidance, respectively; (3)
      overall test-retest reliability (3-day interval) was 0.97; (4) two clearly
      identified factors explained 55.97% of the variance; (5) satisfactory construct
      validity was supported by both factor analysis and theoretically supported
      correlation analysis (significant correlations between the total IES-C and its
      subscales as well as anxiety and depression); and (6) oral cancer patients had
      relatively higher IES-C scores than previously reported. CONCLUSION: These
      results support the IES-C as an instrument with satisfactory psychometric
      properties and ease of use in clinical settings. They also suggest that more
      attention should be paid to the impact on patients of a new diagnosis of oral
      cancer. Further testing of the IES-C in different cancer populations is suggested
      to validate its psychometric properties.

PMID- 15717160
TI  - Sensitivity of dark mutants of various strains of luminescent bacteria to
      reactive oxygen species.
AB  - Recent studies indicated that bioluminescence of the marine bacterium Vibrio
      harveyi may both stimulate DNA repair and contribute to detoxification of
      deleterious oxygen derivatives. Therefore, it was also proposed that these
      reactions can be considered biological roles of bacterial luminescence and might
      act as evolutionary drives in development of luminous systems. However,
      experimental evidence for the physiological role of luciferase in protection of
      cells against oxidative stress has been demonstrated only in one bacterial
      species, raising the question whether this is a specific or a more general
      phenomenon. Here we demonstrate that in the presence of various oxidants
      (hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide and ferrous ions)
      growth of dark mutants of different strains of Vibrio fischeri and Photobacterium
      leiognathi is impaired relative to wild-type bacteria, though to various extents.
      Deleterious effects of oxidants on the mutants could be reduced (with different
      efficiency) by addition of antioxidants, A-TEMPO or 4OH-TEMPO. These results
      support the hypotheses that (1) activities of bacterial luciferases may detoxify
      deleterious oxygen derivatives, and (2) significantly different efficiencies of
      this reaction are characteristic for various luciferases.

PMID- 15717161
TI  - Role of urinary supersaturation in the evaluation of children with urolithiasis.
AB  - Timed urine collections are a standard part of the evaluation for predisposition
      to stone formation in children with urolithiasis. Supersaturation is defined as
      the ratio of the concentration of dissolved salt to its solubility in urine. The
      purpose of the present study was to determine if adding supersaturation to the
      standard timed urine collection increased the ability to detect a metabolic
      predisposition to stone formation. Thirty-two children with urolithiasis had 24
      hour urine measurements of calcium, oxalate, citrate, uric acid, and cystine (the
      "traditional" evaluation), as well as supersaturation for calcium oxalate,
      calcium phosphate, and uric acid, on the same urine sample. Nine (28%) of the 32
      were hypercalciuric, 2 (6%) hyperoxaluric, and 4 (12%) hypocitraturic. In total,
      14 (44%) had a metabolic predisposition that was detected by the traditional
      evaluation. Supersaturation was elevated in 18 (56%), including nine who did not
      have metabolic predisposition detected by traditional evaluation. Urine volume
      was low in 17 (53%) of 32 children, including eight of nine children with
      abnormal supersaturation but normal traditional evaluation. Only one child with
      normal traditional evaluation and normal urine volume had elevated
      supersaturation. These results show that the benefit of adding supersaturation to
      the traditional evaluation was largely negated by consideration of urine volume.

PMID- 15717163
TI  - Catastrophic antiphospholipid syndrome in a 14-year-old child.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease. Less than 1% of
      patients with APS present with life-threatening catastrophic APS (CAPS). We
      report here a case of CAPS in a young girl with cardiac, gastrointestinal and
      renal involvement. Although the management was complicated, the outcome was
      better than expected. We suggest that CAPS be included in the differential
      diagnosis of acute renal failure in children with multi-organ involvement and
      prolonged phospholipid-dependent coagulation time and promptly treated with
      immunomodulating agents and anticoagulants.

PMID- 15717162
TI  - Chronic peritoneal dialysis in Turkish children: a multicenter study.
AB  - Chronic peritoneal dialysis (CPD) has been utilized in the treatment of children
      since 1989 in Turkey. The aims of this study were to summarize our experience
      with CPD in children and to establish a pediatric registry data system in Turkey.
      Standard questionnaires were sent to all pediatric CPD centers. 514 patients
      treated between 1989 and 2002 in 12 pediatric centers were enrolled in the study.
      Reflux nephropathy was the most common (18.1%) cause of renal failure. Mean age
      at dialysis initiation was 10.1+/-4.6 years. Mean duration of dialysis was 24.1+/
      20.5 months. Continuous ambulatory peritoneal dialysis (CAPD) was the first CPD
      modality for 476 (92.6%) patients, 142 of whom switched to automated peritoneal
      dialysis (APD) during follow-up. Currently, 47.3% of the patients are still on
      CPD, 15.4% were transplanted, 13.2% switched to hemodialysis, 16.7% died. The
      patient and technique survivals were 90% and 95% at one year and 70% and 69% at
      five years, respectively. The survival was significantly shorter in the youngest
      age group (0-24 months) compared to those in older age groups (p=0.000). We
      herein report the first results of the TUPEPD study providing information on
      demographic data and survival of pediatric CPD patients. As opposed to clear
      recommendations in favor of APD, there is a clear preponderance of CAPD in our
      pediatric CPD population. That vesicoureteral reflux (VUR) is still the leading
      cause of renal failure is a distressing finding. Remarkably lower survival rates
      and transplantation ratios are as striking and distressing as the high incidence
      of VUR among the causes of ESRD. We conclude that we must make a great effort to
      achieve better results and to change these undesirable events.

PMID- 15717164
TI  - The response to cyclophosphamide in steroid-sensitive nephrotic syndrome is
      influenced by polymorphic expression of glutathion-S-transferases-M1 and -P1.
AB  - Glutathione-S-transferases (GST) play a central role in the inactivation of toxic
      drugs like cyclophosphamide (CP). These enzymes depict several polymorphisms with
      altered activity, and it has been shown that different polymorphisms influence
      the risk of malignancies and the outcome after chemotherapy. To prove the
      hypothesis that CP efficacy in children with nephrotic syndrome is influenced by
      polymorphic expression of GSTs, the genotype of 26 patients was analyzed and
      correlated with the outcome after CP treatment. All 26 children with steroid
      sensitive nephrotic syndrome and frequent relapses or steroid dependency were
      treated with CP at a mean age of 6.7+/-4.0 years. CP was given in a dose of 2
      mg/kg/day for 12+/-1 week. GST-M1, GST-P1 and GST-T1 polymorphisms were detected
      by PCR. In patients with GST-M1 null polymorphism, a significantly better rate of
      sustained remission was seen than in patients with the heterozygous or homozygous
      GST-M1 wildtype (0 versus 29%, P <0.01). In contrast, children with GST-P
      heterozygous or homozygous polymorphism had a significantly lower rate of
      sustained remission compared to homozygous wildtype (7 versus 38%, P <0.02). The
      GST-T1 genotype did not influence the outcome after CP treatment (P =0.32).
      Patients with the combination of GST-M1 null and GST-P1 wildtype did not relapse
      in 50%, compared to 6% in other children (P <0.01). We conclude that the
      polymorphic expression of GST-M1 and -P1 did significantly influence the long
      term remission rate after CP treatment of steroid-sensitive nephrotic syndrome in
      children. Whereas GST-M1 null will increase cyclophosphamide efficacy, GST-P1
      polymorphism seems to be related to enhanced susceptibility to further relapses.

PMID- 15717165
TI  - The use of cyclosporine in a boy with a prior episode of posterior
      encephalopathy.
AB  - We report the case of a 12- year-old Japanese boy who was receiving cyclosporine
      (Cs A) for steroid-dependent nephrotic syndrome despite a prior episode of Cs A
      associated posterior encephalopathy. At the third relapsing of nephrotic
      syndrome, Cs A was initiated. Eight days after the Cs A therapy, the boy was
      admitted to the University Hospital of Tsukuba because of generalized convulsion.
      Magnetic resonance imaging (MRI) showed hyperintense lesions involving the
      bilateral parieto-occipital region. Cs A was discontinued, and cyclophosphamide
      was started. The boy had a 6-month drug-free period after the cyclophosphamide
      treatment and then relapsed three more times in the following 5 months. As the
      prednisolone dosage could not be decreased to less than 2 mg/kg/48 h, the patient
      was re-challenged with Cs A 1 1/2 years later. Blood pressure and serum Cs A
      levels were measured frequently, an anti-hypertensive drug was given, and MRI was
      done four times to detect hyperintense lesions. He has been receiving Cs A for 9
      months, and MRI has revealed no abnormalities. At the latest follow-up, dated 12
      April 2004, he was in a remissive state of nephrotic syndrome. This is the first
      report of giving Cs A to a nephrotic child who had a previous history of Cs A
      associated posterior encephalopathy.

PMID- 15717167
TI  - Renal cysts and nephrocalcinosis in a patient with Bartter syndrome type III.
AB  - Chronic hypokalemia is known to induce renal cyst formation in some diseases
      including primary aldosteronism, distal renal tubular acidosis, Liddle disease
      and apparent mineralocorticoid excess syndrome. Although chronic hypokalemia is
      the main clinical feature of Bartter syndrome, renal cyst formation in this
      disease has never been reported. We describe a patient with classic Bartter
      syndrome who exhibited renal cysts and nephrocalcinosis. Direct sequencing
      analysis of the chloride channel CLC-Kb gene identified a heterozygous nonsense
      mutation (W610X) in exon 16 indicating a diagnosis of Bartter syndrome type III.
      Although the precise mechanism underlying the development of renal cysts in our
      patient remains unclear, chronic hypokalemia and nephrocalcinosis may contribute
      to cyst development.

PMID- 15717169
TI  - Microfluidics in China.

PMID- 15717166
TI  - Glucose transporters in diabetic nephropathy.
AB  - Changes in glucose transporter expression in glomerular cells occur early in
      diabetes. These changes, especially the GLUT1 increase in mesangial cells, appear
      to play a pathogenic role in the development of ECM expansion and perhaps other
      features of diabetic nephropathy. In addition, it appears that at least some
      diabetic patients may be predisposed to nephropathy because of polymorphisms in
      their GLUT1 genes. GLUT1 overexpression leads to increased glucose metabolic flux
      which in turn triggers the polyol pathway and activation of PKC alpha and B1.
      Activation of these PKC isoforms can lead directly to AP-1 induced increases in
      fibronectin expression and ECM accumulation. Other, more novel effects of GLUT1
      on cellular hypertrophy and injury could also promote changes of diabetic
      nephropathy. Strategies to prevent GLUT1 overexpression could ameliorate or
      prevent the progression of diabetic nephropathy.

PMID- 15717170
TI  - Enantioselective separations by packed column subcritical and supercritical fluid
      chromatography.
AB  - Enantioselective separations have been one of the most successful applications of
      supercritical fluid chromatography (SFC). Although analytical scale separations
      have dominated the literature, the use of SFC for preparative chiral separations
      is growing. Both analytical and preparative scale SFC separations seek to take
      advantage of the high efficiency, high throughput, and rapid method development
      associated with the technique. This review will cover recent developments in the
      application of SFC to enantioseparations.

PMID- 15717168
TI  - Infantile systemic lupus erythematosus presenting with pulmonary hemorrhage.
AB  - Systemic lupus erythematosus in infants born to healthy mothers is a rare entity.
      We describe a male infant who presented at 1 month of age with pulmonary
      hemorrhage and glomerulonephritis due to systemic lupus erythematosus, confirmed
      serologically and histologically. He was managed with a combination of prednisone
      and intermittent cyclophosphamide, but also received mycophenolate mofetil, with
      a complete serological and clinical remission at 30-month follow-up. This case
      underscores the importance of a broad approach to the evaluation of pulmonary
      hemorrhage and glomerulonephritis in the very young and the need for aggressive
      immunosuppressive therapy to achieve sustained serological and clinical
      remission.

PMID- 15717171
TI  - Fast electrophoresis in conventional capillaries by employing a rapid injection
      device and contactless conductivity detection.
AB  - A purpose-made set-up featuring an automated fast injector allowed the easy
      optimization of the injected amount and the adjustment of the separation length
      of conventional capillaries from a minimum of 5 cm upward. It was found that a
      compromise in capillary length for separation efficiency and analysis time also
      has to take into account the injected amount, which in turn affects the
      sensitivity and hence the detection limit. The versatility of the system was
      demonstrated by the analysis of the major cations and anions in natural water
      samples in less than 1 min, the concurrent determination of a mixture of amino
      acids and carbohydrates in 160 s, and of three active ingredients in a
      pharmaceutical preparation in 40 s. Plate numbers were typically around 50,000
      and detection limits down to 1 muM could be achieved.

PMID- 15717172
TI  - Characterization of [3Fe-4S] ferredoxin DbfA3, which functions in the angular
      dioxygenase system of Terrabacter sp. strain DBF63.
AB  - Dibenzofuran 4,4a-dioxygenase (DFDO) from Terrabacter sp. strain DBF63 is
      comprised of three components, i.e., terminal oxygenase (DbfA1, DbfA2), putative
      [3Fe-4S] ferredoxin (ORF16b product), and unidentified ferredoxin reductase. We
      produced DbfA1 and DbfA2 using recombinant Escherichia coli BL21(DE3) cells as a
      native form and purified the complex to apparent homogeneity. We also produced
      and purified a putative [3Fe-4S] ferredoxin encoded by ORF16b, which is located
      2.5 kb downstream of the dbfA1A2 genes, with E. coli as a histidine (His)-tagged
      form. The reconstructed DFDO system with three purified components, i.e.,
      DbfA1A2, His-tagged ORF16b product, and His-tagged PhtA4 (which is a tentative
      reductase derived from the phthalate dioxygenase system of strain DBF63) could
      convert fluorene to 9-fluorenol (specific activity: 14.4 nmol min(-1) mg(-1)) and
      convert dibenzofuran to 2,2',3-trihydroxybiphenyl. This indicates that the ORF16b
      product can transport electrons to the DbfA1A2 complex; and therefore it was
      designated DbfA3. Based on spectroscopic UV-visible absorption characteristics
      and electron paramagnetic resonance spectra, DbfA3 was elucidated to contain a
      [3Fe-4S] cluster. Ferredoxin interchangeability analysis using several types of
      ferredoxins suggested that the redox partner of the DbfA1A2 complex may be rather
      specific to DbfA3.

PMID- 15717173
TI  - Chlorogenate hydrolase-catalyzed synthesis of hydroxycinnamic acid ester
      derivatives by transesterification, substitution of bromine, and condensation
      reactions.
AB  - A chlorogenate hydrolase (EC 3.1.1.42) synthesized 2-phenylethyl caffeate (2
      CAPE) from 5-chlorogenic acid (5-CQA) and 2-phenylethyl alcohol (2-PA) (by
      transesterification), from 5-CQA and 2-phenylethyl bromide (2-PBr) (by
      substitution of bromine), and from caffeic acid (CA) and 2-PA or 2-PBr (by
      condensation) as well as hydrolysis of 5-CQA. Some reaction conditions including
      pH, temperature, substrate and solvent concentrates, and reaction time were
      optimized for the production of 2-CAPE. A maximal molar yield of 50% was achieved
      by transesterification, 4.7% by substitution of bromine, and 13% by condensation.
      Among the parameters studied for optimization, the pH of the buffer solution and
      concentration of 2-PA or 2-PBr affected the production of 2-CAPE. The optimum pH
      for the hydrolysis reaction was within the neutral range (pH 6.5), whereas the
      residual three reactions were only catalyzed within the acidic range (pH 3.0
      4.0). The optimum concentrations of 2-PA and 2-PBr for three reactions were 5-70
      vol% and no 2-CAPE was produced in the 2-PA or 2-PBr solutions containing
      powdered enzyme. The enzyme may bind to the caffeoyl moiety of 5-CQA or CA to
      form an enzyme-substrate complex. It then catalyzes four different reactions
      corresponding to the reaction conditions.

PMID- 15717174
TI  - [Evidence-based medicine and the Cochrane Skin Group].
AB  - The concept of evidence based medicine (EBM) has represented a paradigm shift in
      medical thinking and practise in the last decade. However, we seem to be stuck
      with the phrase, yet it is a term that is frequently abused and misunderstood.
      Therefore, the purpose of this article is to clarify what evidence based
      dermatology (EBD) is and what it is not. Some guidance on the four key steps in
      practising EBM in dermatology will be given. The central role of systematic
      reviews will be elaborated and the Cochrane skin group introduced. Finally, the
      limitation of EBD will be discussed.

PMID- 15717175
TI  - Early recognition of basal cell naevus syndrome.

PMID- 15717176
TI  - Early recognition of basal cell naevus syndrome.
AB  - The basal cell naevus syndrome is an autosomal dominant syndrome characterised by
      major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar
      pits, and intracranial calcifications. Early recognition is important in order to
      reduce morbidity due to cutaneous and cerebral malignancy and oromaxillofacial
      deformation and destruction, although diagnosis in infancy is rare. We describe
      three unrelated children with basal cell naevus syndrome who appeared to be the
      first patient in each family. CONCLUSION: Our observations lead us to recommend
      looking for other manifestations of this disease in patients who present with
      cardiac fibroma, cleft lip/palate, polydactyly or macrocephaly. Bifid, fused or
      splayed ribs should be considered a major criterion of great help in establishing
      a diagnosis, particularly in young children.

PMID- 15717177
TI  - Serum carnitine levels in patients with homozygous beta thalassemia: a possible
      new role for carnitine?
AB  - Carnitine (beta-hydroxy-gamma-trimethylaminobutyric acid) facilitates the
      transfer of activated long-chain fatty acids from the cytoplasm to the
      mitochondria, the site of their beta-oxidation. Carnitine deficiency results in a
      reduced usage of fatty acids in energy production and therefore the appearance of
      clinical symptoms such as myalgia and muscle weakness. In the present study,
      serum carnitine levels were measured in 45 children and 20 adults with homozygous
      beta thalassemia. A decrease in serum carnitine levels (total, free and acyl) was
      found, without any evidence of disorder in the process of mitochondrial beta
      oxidation. The possible cause of this finding could be related to a reduced
      hepatic carnitine biosynthesis. CONCLUSION: In patients with homozygous beta
      thalassemia, the reduction of serum carnitine levels might play an important role
      in the appearance of muscular dysfunction. It is possible that L : -carnitine
      administration in these patients might improve or even resolve the aforementioned
      symptom.

PMID- 15717178
TI  - A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus
      arteriosus.
AB  - Ibuprofen (IBU) has previously been shown to be as effective as indomethacin
      (INDO) in closing the patent ductus arteriosus (PDA) of preterm infants, without
      severely affecting renal hemodynamics or basal cerebral blood flow. We conducted
      a meta-analysis of randomized trials to compare the efficacy and safety of IBU
      and INDO for treatment of PDA. Data from the nine relevant trials ( n =566),
      showed no significant difference in the efficacy of IBU and INDO in PDA closure (
      P =0.70). However, five trials ( n =443) provided serum creatinine concentration
      data that revealed a significantly lower increase favoring IBU ( P < 0.001), and
      urine output data that showed a significantly lower decrease favoring IBU ( P <
      0.001). In two trials ( n =188) the proportion of infants who required postnatal
      oxygen therapy at 28 days (defined as chronic lung disease) was significantly
      higher with IBU (52/94; 55.3%) than with INDO (38/94; 40.4%, P < 0.05). No
      statistically significant differences were found in mortality, intraventricular
      hemorrhage, necrotizing enterocolitis, surgical ligation, sepsis, retinopathy of
      prematurity, periventricular leukomalacia, length of hospital stay,
      gastrointestinal bleeding, re-opening of PDA, back-up treatment, surfactant
      therapy, or days on a ventilator. CONCLUSION: ibuprofen and indomethacin have
      similar efficacy in patent ductus arteriosus closure, but preterm infants treated
      with ibuprofen experience lower serum creatinine values, higher urine output, and
      less undesirable decreased organ blood flow and vasoconstrictive adverse effects.

PMID- 15717179
TI  - Extensive primary cutaneous herpes simplex virus type 1 infection in an infant
      following acute rotavirus gastroenteritis.

PMID- 15717180
TI  - Acute pancreatitis with Kawasaki disease: analysis of cases with elevated serum
      amylase levels.

PMID- 15717181
TI  - Autoimmune haemolytic anaemia and renal Fanconi syndrome caused by valproate
      therapy.

PMID- 15717182
TI  - 1p36 deletion syndrome with intestinal malrotation and annular pancreas.

PMID- 15717183
TI  - [Introduction of a mammography screening program in Germany. Consideration of
      benefits and risks].
AB  - For women between 50 and 70 years of age, X-ray mammography presently represents
      the most effective method for early breast cancer detection. It is commonly
      accepted that quality assured mammography examinations conducted at regular
      intervals can reduce mortality from breast cancer. In the year 2002, the German
      Bundestag agreed to the implementation of a mammography screening program for
      Germany based on the European guidelines. The effectiveness of a mammography
      screening program is controversially discussed and two of the most commonly cited
      hazards are the occurrence of false-positive results and the so-called
      overdiagnosis. Another issue of criticism is the radiation risk due to the
      mammography examinations. However, in women aged 50-70 years the radiation risk
      has no substantial importance. In contrast to the present situation in Germany in
      which opportunistic screening is widespread, standardized quality assured
      screening will guarantee that false-positive rates are kept as low as possible
      and that further assessment diagnostics are effective and minimally invasive.

PMID- 15717184
TI  - [Palivizumab in viral respiratory infections].

PMID- 15717185
TI  - [Early diagnosis of chronic systemic inflammatory disorders].
AB  - Functionally relevant damage caused by chronic systemic inflammatory disorders of
      autoimmune and/or unknown origin can be reduced or sometimes avoided by early
      initiation of treatment. This requires a correct diagnosis which makes treatment
      as early as possible. Due to the often uncharacteristic symptoms at the onset of
      disease, early diagnosis in systemic inflammatory disorders represents a
      diagnostic challenge. This review outlines current standards and limitations in
      the early diagnosis of rheumatoid arthritis, collagen vascular diseases and
      primary systemic vasculitides. Recent advances especially in serology and imaging
      techniques have improved early diagnosis of systemic inflammatory disorders.

PMID- 15717186
TI  - [Management of acute pulmonary failure: diagnostics-ventilation-withdrawal].
AB  - Acute pulmonary failure by definition excludes cardiac insufficiency as the
      pathogenetic mechanism involved in the development of acute lung injury (ALI) and
      acute respiratory distress syndrome (ARDS). The systemic inflammatory reaction
      underlying acute pulmonary failure has many etiological causes. One of the most
      important trigger mechanisms is sepsis. In the realm of cardiac intensive care
      medicine, the systemic inflammatory reaction is observed in conjunction with
      assist systems, during extracorporeal circulation, or in the course of
      cardiogenic shock. In the end, even mechanical ventilation itself can elicit an
      inflammatory reaction and result in pulmonary failure through ventilator
      associated lung injury. Knowledge of the mechanisms has led to the concept of
      protective ventilation, which exerts both prophylactic and therapeutic effects.
      Protective ventilation is an integral part of a bundle of therapeutic intensive
      care measures. Both constitute the essence of management of acute pulmonary
      failure.

PMID- 15717188
TI  - Non-traumatic acute myelopathy due to cervical disc herniation in contiguous two
      level disc spaces: a case report.
AB  - Non-traumatic acute myelopathy caused by cervical disc herniation is rare, and no
      case has been reported which the disease was caused by the extrusion or migration
      of a cervical disc herniation of contiguously-located two-level disc space. In
      this report, the disease is described, and the direction of migration and
      surgical treatment of the disease are discussed.

PMID- 15717187
TI  - Cross-cultural adaptation and validation of the NASS outcomes instrument in
      Spanish patients with low back pain.
AB  - OBJECTIVES: The aim of the study was to evaluate validity, reliability,
      responsiveness and practicality of the NASS-AAOS (North American Spine Society-
      American Academy of Orthopaedic Surgeons) questionnaire in patients with low back
      pain. METHODS: The sample included 70 patients with herniated disk, stenosis,
      chronic low back pain of unknown etiology or acute low back pain. They were
      assessed twice before treatment (test--retest) and a third measure six months to
      one year afterwards. RESULTS: The mean time of administration was 24 and 20 min
      for the test and post-treatment evaluation, respectively. Cronbach's alpha
      coefficient was between 0.78 and 0.92 on the baseline test and 0.90 or higher on
      the post-treatment evaluation. The test--retest reproducibility was 0.95 (0.91-
      0.98) for 'neurological symptoms', 0.82 (0.63--0.91) for 'pain/disability' and
      0.63 (0.25--0.82) for 'expectations'. The associations with other measures and
      clinical criteria were generally moderate to high and in the expected direction.
      The effect size for 'pain/disability' in combination with 'neurological symptoms'
      was 2.02 for patients who improved versus an effect of -0.09 in patients who were
      stable between test and retest; the area under the curve on this joint scale was
      0.81 (0.69--0.90). CONCLUSIONS: The instrument is valid, sensitive to clinical
      changes and reliable for comparisons between groups, but further study is needed
      for its application in monitoring individual patients.

PMID- 15717189
TI  - Single-blinded prospective randomized study comparing open versus needle
      technique for obtaining autologous cancellous bone from the iliac crest.
AB  - One of the most frequent complications of cervical anterior discectomy with
      fusion is pain at the donor site, usually the iliac crest. Despite the advent of
      new materials, autologous bone is still the "gold standard" for fusion
      procedures. A prospective, single blinded, randomized study was performed to
      evaluate the effect of a minimal invasive technique to obtain autologous bone
      from the iliac crest on pain. The minimal invasive technique uses a large needle
      to obtain cancellous bone. Consecutive patients scheduled for cervical anterior
      discectomy with a fusion using a cage were randomly assigned either to the
      classical open group or the needle group. Patients were unaware of the two
      possible options for obtaining autologous bone. They were asked to fill in visual
      analogue scores (VASs) at fixed moments during the first 6 weeks postoperatively.
      Three VASs were recorded: the score at the moment, the minimal score and the
      maximal score during the last 24 h. The wound at the iliac crest was measured 6
      weeks postoperatively. Complications were registered. Fifty patients were
      enrolled. Twenty-five patients were assigned to each group . The pain scores from
      the needle group were significantly less than from the open group. At 2 weeks
      postoperatively, nearly all patients (88%) of the needle group were free of pain
      at the iliac crest, whereas ten patients (40%) of the open group still had some
      pain. Complications only occurred in the open group. Six patients complained of
      diminished sensibility. In two cases, it had resolved at 6 weeks postoperatively.
      In one case, a hemorrhage occurred. Surgical evacuation was not necessary.
      Obtaining autologous cancellous bone through a large needle for filling a
      cervical cage (even multiple cages) is safe and evidently less painful than
      through a classical open procedure. If pain exists it does not last very long.
      Generally, the pain is resolved within 2 weeks.

PMID- 15717190
TI  - Effects of unisegmental disc compression on adjacent segments: an in vivo animal
      model.
AB  - It is controversial whether fusion of discs in the spine leads to increased
      degeneration on the remaining discs or whether the degenerative changes are
      merely a part of the inevitable natural history process. To determine the effects
      of unisegmental compression and subsequent recovery on adjacent segments, we
      studied histology, radiology and intradiscal pressure using an in vivo rabbit
      model. Fifteen New Zealand rabbits were divided in to three groups of five. In
      the first group, the intervertebral disc L4-L5 of the lumbar spine was axially
      loaded for 28 days with an external loading device. In the second group, the
      intervertebral disc was compressed for 28 days and allowed to recover for an
      equal amount of time, with the loading device removed. Five animals underwent a
      sham operation, in which the external loading device was situated, but their
      discs remained unloaded for 28 days. The intradiscal pressure was determined in
      the loaded discs as well as in the cranial and caudal adjacent discs. Lateral
      radiographs were taken from each subjected intervertebral disc with adjacent
      vertebral bodies and the cranial and caudal adjacent segments. The compressed
      discs showed lower intradiscal pressure in comparison with the control group,
      which remained unloaded. In the cranial and caudal discs adjacent to the loaded
      discs the average intradiscal pressure was similar to the unloaded controls. The
      loaded discs demonstrated a significant decrease in disc space. No discs adjacent
      to the loaded discs changed in height. The lamellar architecture of the inner,
      middle, and outer annulus became more disorganized in the loaded discs. The
      nucleus pulposus showed increase of mucoid degeneration and increased cell death.
      Intervertebral discs from the control group and the adjacent discs to the
      compressed discs maintained their normal morphology. This study shows that
      mechanical loading of discs in the spine can cause rapid degeneration. Adjacent
      discs, however, did not change in terms of radiology, intradiscal pressure, or
      histology.

PMID- 15717191
TI  - Comparison of the biomechanical effects of posterior and anterior spine
      stabilizing implants.
AB  - Posteriorly and anteriorly fixed implants for stabilizing unstable spines are
      available on the market. Differences in the biomechanical behavior of these
      implant types are not yet fully clear. They were investigated using three
      dimensional nonlinear finite element models of the lumbar spine in an intact
      state, with an anteriorly fixed MACS-TL implant and with posteriorly fixed
      internal fixators. The bisegmental implants spanned the L3 vertebra, and bone
      grafts were used with both implant types to replace parts of the two bridged
      discs. The computer models were loaded with partial body weight and muscle forces
      simulating standing, flexion, extension and axial rotation. Both implant types
      have reduced intersegmental rotation for flexion, extension, and axial rotation
      in the bridged region. The reduction is more pronounced for the MACS-TL implant.
      The implant type has only a minor effect on intradiscal pressure. Maximum von
      Mises stresses in the vertebrae are lower for flexion and extension with the MACS
      TL implant than with the internal fixator. Very high stresses are predicted for
      flexion after insertion of internal fixators. For standing and torsion, maximum
      stresses differ only negligibly between the two implant types. In the period
      immediately after surgery, patients with osteoporotic vertebrae and who are
      treated with an internal spinal fixation device should therefore avoid excessive
      flexion. This study adds new information about the mechanical behavior of the
      lumbar spine after insertion of posterior and anterior spine-stabilizing
      implants. This information improves our biomechanical understanding of the spine.

PMID- 15717192
TI  - [Results of the Collaborative Initial Glaucoma Treatment Study (CIGTS)].
AB  - The Collaborative Initial Glaucoma Treatment Study (CIGTS) was initiated to
      evaluate whether local medical therapy or trabeculectomy is the better initial
      treatment for patients with newly diagnosed open-angle glaucoma. Visual field
      progression, intraocular pressure, and visual acuity were to be monitored for a
      period of 5 years. A total of 607 patients were randomly distributed among the
      two groups and controlled at 6-month intervals. At the same time the
      investigators tried to record quality of life using a questionnaire. Both
      trabeculectomy and medical therapy were able to lower intraocular pressure
      significantly, whereas trabeculectomy was more effective. The results of the
      questionnaire showed only minor differences between the two groups. The medically
      treated patients reported slightly more ocular symptoms than the patients in the
      trabeculectomy group.

PMID- 15717193
TI  - Approaching the self-incompatibility locus Z in rye (Secale cereale L.) via
      comparative genetics.
AB  - Using barley and wheat expressed sequence tags as well as rice genomic sequence
      and mapping information, we revisited the genomic region encompassing the self
      incompatibility (SI) locus Z on rye chromosome 2RL applying a comparative
      approach. We were able to arrange 12 novel sequence-tagged site (STS) markers
      around Z, spanning a genetic distance of 32.3 cM, with the closest flanking
      markers mapping at a distance of 0.5 cM and 1.0 cM from Z, respectively, and one
      marker cosegregating with Z, in a testcross population of 204 progeny. Two
      overlapping rice bacterial artifical chromosomes (BACs), OSJNBa0070O11 and
      OSJNBa0010D21, were found to carry rice orthologs of the three rye STS markers
      from the 1.5-cM interval encompassing Z. The STS-marker orthologs on these rice
      BACs span less than 125,000 bp of the rice genome. The STS marker TC116908
      cosegregated with Z in a mapping population and revealed a high degree of
      polymorphism among a random sample of rye plants of various origin. TC116908 was
      shown via Southern hybridization to correspond to gene no. 10 (OSJNBa0070O11.10)
      on rice BAC OSJNBa0070O11. Reverse transcription-PCR with a TC116908-specific
      primer pair resulted in the amplification of a fragment of the expected size from
      the rye pistil but not from leaf cDNA. OSJNBa0070O11.10 was found to show a
      highly significant sequence similarity to AtUBP22, a ubiquitin-specific protease
      (UBP). TC116908 likely represents a putative UBP gene that is specifically
      expressed in rye pistils and cosegregates with Z. Given that the ubiquitination
      of proteins is emerging as a general mechanism involved in different SI systems
      of plants, TC116908 appears to be a promising target for further investigation
      with respect to its relation to the SI system of the grasses.

PMID- 15717194
TI  - Detection of infectious colitis by 18F-fluorodeoxyglucose-positron emission
      tomography in a child receiving intensive care after cardiac surgery.
AB  - Pyrexia of unknown origin (PUO) and suspected focal infection/inflammation are
      challenging medical problems. Nuclear medicine methods using scintigraphy with
      (111)In- or (99m)Tc-labelled antibodies or (67)Ga-citrate have been validated for
      the diagnosis and detection of inflammatory processes. Recently, positron
      emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has been described
      as a promising imaging method, especially for PUO. We report the use of FDG-PET
      in an 18-month-old boy that revealed unexpected infectious colitis after cardiac
      surgery. This case suggests that FDG-PET is a valuable tool for the detection of
      unknown inflammatory foci in childhood, especially when the time needed for
      examination and radiation exposure are to be considered.

PMID- 15717195
TI  - A meniscus causing painful snapping of the elbow joint: MR imaging with
      arthroscopic and histologic correlation.
AB  - Snapping of the elbow joint can cause pain. We report a case of painful snapping
      elbow produced by an interposed meniscus in the radiohumeral joint in a 20-year
      old man. The MR arthrogram demonstrated a meniscus-like tissue interposed between
      the radial head and humeral capitellum. The MR-arthrographic findings were well
      correlated with surgical findings. The location and appearance of the meniscus
      like tissue was similar to that of meniscus in the knee joint. Histologic
      findings of the excised meniscus-like tissue showed a typical presentation of
      fibrocartilage. A meniscus may exist in the elbow joint and can be a rare cause
      of painful snapping elbow. MR arthrography is helpful for identifying the
      snapping tissue in the elbow joint.

PMID- 15717196
TI  - Clinical and radiological deterioration in a patient with AIDS.
AB  - Paradoxical clinical deterioration of miliary tuberculosis, characterized by
      pulmonary and abdominal manifestations, is reported in a patient with the
      acquired immunodeficiency syndrome, after initiation of treatment with highly
      active antiretroviral therapy. Paradoxical reaction was attributed to partial
      restoration of cell-mediated immunity related to highly effective antiretroviral
      therapy. Because tuberculosis has a high prevalence in HIV patients and
      tuberculosis is often characterized by miliary spreading of disease in these
      patients, it is important to recognize this phenomenon.

PMID- 15717197
TI  - Lobar mucinous bronchioloalveolar carcinoma of the lung showing negative FDG
      uptake on integrated PET/CT.
AB  - We present a case of bronchioloalveolar carcinoma manifesting as air-space
      consolidation with negative FDG uptake on integrated PET/CT in a 42-year-old
      woman. To know this pattern of uptake especially in the case of mucin-predominant
      lobar bronchioloalveolar carcinoma may help avoid misdiagnosis of this particular
      tumor.

PMID- 15717198
TI  - Experimental inflammation of the rat distal colon inhibits ion secretion in the
      proximal colon by affecting the enteric nervous system.
AB  - Intestinal inflammation causes hyporesponsiveness of the inflamed tissue to
      secretagogues but little is known about the behaviour of the areas proximal to
      the site of inflammation. We studied the responses of the proximal segment of the
      colon to carbachol, histamine, isobutylmethylxanthine (IBMX) and vasoactive
      intestinal peptide (VIP) in rats with trinitrobenzenesulphonic acid (TNBS)
      induced, chronic inflammation of the distal colon. Macroscopic and biochemical
      analysis ruled out the presence of inflammation in the proximal colon. When
      mounted in Ussing chambers under voltage-clamp conditions, basal transport and
      conductance were not affected. However, the maximum response in the
      concentration/response curves (short-circuit current) for carbachol and histamine
      was reduced in TNBS-treated rats, without changes in the EC(50). This effect
      corresponded to reduced chloride secretion, as demonstrated by ion substitution
      experiments. The responses to IBMX and VIP were virtually unaffected. The
      inhibitory effect was abolished by pretreatment with the neural blockers
      tetrodotoxin and lidocaine but not indomethacin, suggesting that the enteric
      nervous system is responsible for the inhibition. In conclusion, chronic distal
      inflammation of the distal colon results in inhibition of calcium-dependent
      secretion in the proximal colon via a reduction of the contribution of the
      enteric nervous system.

PMID- 15717199
TI  - Finding the unexpected: pathological examination of surgically resected femoral
      heads.
AB  - OBJECTIVE: To study the clinically diagnosed disease process but also identify
      additional, clinically undetected pathologies in femoral heads resected for
      replacement arthroplasty. DESIGN AND MATERIAL: A retrospective review was carried
      out of the pathological findings in 460 surgically resected femoral heads. Serial
      sections were submitted to low-energy fine-detail radiography, then decalcified
      sections stained by the WHO method were examined. The preoperative clinical and
      imaging diagnoses were compared with the pathological findings and special
      interest was placed on assessing the clinical significance of any unexpected,
      clinically undetected findings. RESULTS: The most common findings included the
      presence of bone islands (solitary osteomas) and areas of avascular necrosis in
      addition to the primary joint disease for which the patient underwent surgery.
      The preoperative symptomatology did not distinguish between the known primary
      disease and the additional pathological findings. CONCLUSION: Some of the
      clinically unidentified lesions were of a size that fell below the ability of
      current clinical investigations to detect. However, the finding of lesions by
      tissue fine-detail radiography indicates that current, more sensitive clinical
      imaging techniques may identify them. Careful examination of surgically resected
      femoral heads is important to ensure that all pathologies are identified and
      assessed for clinical relevance.

PMID- 15717200
TI  - Evaluation of chronological age based on third molar development in the Spanish
      population.
AB  - A cross-sectional study was carried out to assess chronological age estimation
      based on the stages of third lower molar development, following the eight stages
      (A-H) method of Demirjian et al. The final sample consisted of 1,054
      orthopantomograms from Spanish individuals of known chronological age (range 14
      21 years) and gender (462 males and 592 females). Results showed a stronger
      correlation for males (r(2)=0.54) than for females (r(2)=0.45). Root formation
      occurred earlier in males than females, in stages 5, 6 and 7. The mean difference
      between chronological and estimated age was -0.10 years (+/-1.23 SD) for left
      third molar, and -0.07 years (+/-1.22 SD) for right third molar, with slight
      variations regarding sex. Comparative tables are provided regarding medicolegal
      questions concerning age 18 prediction in the Spanish population, showing that
      legal age is reached in stage 7 (G) by women and in stage 8 (H) by men. No
      differences have been observed between sides (p<0.0001). Differences were
      observed between Spaniards and other previously studied populations. Third molar
      maturity takes place earlier in the Spanish than French-Canadian, Scandinavian,
      American, German, Japanese and South African populations and is more similar to
      US Hispanics in root development.

PMID- 15717201
TI  - DNA mixtures: biostatistics for mixed stains with haplotypic genetic markers.
AB  - The conventional theory for interpreting forensic DNA evidence developed for the
      autosomal genetic markers is not applicable in the case of haplotypic markers,
      specifically for Y-STR based data. The reason is, that in contrast to the case of
      autosomal markers, single alleles found in the mixed stain cannot be assigned to
      unknown stain contributors independently of each other, while the assignable
      entities are sets of linked alleles which should be treated as non-separable
      units. It is shown that the conventional theory cannot be extended to this
      situation. A novel theory which accounts for the features of haplotypic markers
      has been developed within the general framework of the hypotheses testing
      approach. This theory opens the way for the use of haplotypic markers in the
      analysis of mixed stains with the arbitrary numbers of unknown contributors and
      linked loci. A numerical example demonstrates the application of the theory.

PMID- 15717202
TI  - Genotype, enzyme activity, glutathione level, and clinical phenotype in patients
      with glutathione synthetase deficiency.
AB  - Glutathione synthetase (GS) deficiency is a rare autosomal recessive disorder.
      The clinical phenotype varies widely, and nearly 30 different mutations in the
      GSS gene have been identified. In the present study, genotype, enzyme activity,
      metabolite levels and clinical phenotype were evaluated in 41 patients from 33
      families. From some of the patients, data on glutathione (GSH) levels and gamma
      glutamylcysteine levels in cultured fibroblasts were also available. Twenty-seven
      different mutations were found: 14 missense, 9 splice, 2 deletions, 1 insertion
      and 1 nonsense mutation. Twenty-three patients were homozygous and 18 were
      compound heterozygous. The moderate and severe clinical phenotypes could not be
      distinguished based on enzyme activity, GSH or gamma-glutamylcysteine levels in
      cultured fibroblasts. However, in fibroblasts, the residual GS activity was
      correlated with the GSH level. All mutations causing frameshifts, premature stop
      codons or aberrant splicing were associated with moderate or severe clinical
      phenotypes including haemolytic anaemia, 5-oxoprolinuria, and (in several forms)
      neurodevelopmental signs. The data indicate that additional genetic or
      environmental factors modify at least the moderate and severe phenotypes and that
      the clinical classification given to the patients may be influenced by variation
      in follow-up. The type of mutation involved can, to some extent, predict a mild
      versus a more severe phenotype.

PMID- 15717203
TI  - Molecular analysis of congenital scoliosis: a candidate gene approach.
AB  - The etiology of congenital scoliosis is largely unknown. The severe vertebral
      disorder, spondylocostal dysostosis type 1, is associated with a homozygous delta
      like 3 (DLL3) mutation. Scoliosis has been observed in a heterozygous DLL3
      carrier, raising the possibility of its involvement in congenital scoliosis. We
      present the first molecular study of congenital scoliosis by analysis of the
      candidate gene DLL3 and demonstrate one novel missense variant. However, no novel
      or previously described mutations are present in our cohort, indicating that DLL3
      mutations may not be a major cause of congenital scoliosis. Additionally, we have
      evaluated patients with congenital scoliosis not diagnosed with a known syndrome
      and identified a significant number of associated renal and cardiac anomalies and
      familial incidence of idiopathic scoliosis in this group.

PMID- 15717204
TI  - tantalus, a potential link between Notch signalling and chromatin-remodelling
      complexes.
AB  - The tantalus (tan) gene encodes a protein that interacts specifically with the
      Polycomb/trithorax group protein Additional sex combs (ASX). Both loss-of
      function and gain-of-function mutations in tan cause tissue-specific defects in
      the eyes, wing veins and bristles of adult flies. As these defects are also
      typical for components of the Notch (N) signalling pathway, we wished to
      determine if TAN interacts with this pathway. Through careful examination of
      ectopic tan phenotypes, we find that TAN specifically disrupts all three major
      processes associated with the N signalling pathway (boundary formation, lateral
      inhibition, and lineage decisions). Furthermore, ectopic tan expression abolishes
      expression of two N target genes, wingless (wg) and cut, at the dorsal-ventral
      boundary of the wing. An interaction between tan and N was also observed using a
      genetic assay that previously detected interactions between tan and Asx. The
      previously observed ability of TAN to move between the cytoplasm and nucleus, and
      to associate with DNA, provides a potential mechanism for TAN to respond to N
      signalling.

PMID- 15717205
TI  - Stapled gastroplasty for antral stricture after repair of neonatal gastric
      rupture: report of a case.
AB  - The patient was the second of twin girls born at 32 weeks' gestation, weighing
      1736 g. Abdominal distention was noted the day after birth, and abdominal x-ray
      showed free air in the abdomen. An emergent laparotomy with debridement and
      primary closure were performed for spontaneous gastric rupture. From the age of 8
      months, the infant sometimes vomited after meals and was unable to gain weight.
      She was diagnosed, by upper gastrointestinal series and gastroscopy, with antral
      stricture with a normal prepyloric area and pylorus. The presence of an antral
      web, ulcers, or ectopic pancreatic tissue was excluded. There was sufficient
      distance between the stricture area and the pylorus. Stapled gastroplasty using
      an Endopath linear cutter stapler and a Proximate linear stapler was performed
      safely and quickly without injury to the normal pylorus or branches of the vagal
      nerve at the lesser curvature. The child's postoperative course was uneventful.

PMID- 15717206
TI  - HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining
      fluid cytokines. A randomized controlled trial.
AB  - OBJECTIVE: Ventilation strategies for preterm neonates may influence the severity
      of pulmonary dysfunction and later development of chronic lung disease. The
      objective of this report is to compare the effects of high-frequency oscillatory
      ventilation (HFOV) versus synchronized intermittent mandatory ventilation (sIMV)
      from the points of views of biochemical and functional variables. DESIGN:
      Randomized controlled trial. SETTING: Third level NICU. PATIENTS AND
      PARTICIPANTS: Forty preterm neonates with a gestational age of 24-29 weeks were
      randomly assigned to one of the two above-mentioned ventilation strategies within
      30 min from birth. MEASUREMENTS AND RESULTS: At 1, 3, 5, and 7 days, the babies
      were monitored by means of ventilator indices, pulmonary function, and eight pro
      inflammatory or anti-inflammatory cytokines measured in bronchoalveolar lavage
      fluid. The neonates assigned to the HFOV procedure benefited from early and
      sustained improvement in pulmonary mechanics and gas exchange-significantly
      higher dynamic respiratory compliance values, significantly lower expiratory
      airway resistance and oxygenation index values-with earlier extubation as
      compared to the neonates assigned to sIMV treatment, and showed significantly
      lower transforming growth factor-beta1 concentrations in bronchoalveolar lavage
      fluid. CONCLUSIONS: The results of this randomized clinical trial support the
      hypothesis that early and exclusive use of HFOV, combined with optimum volume
      strategy, has a beneficial effect during the acute phase of lung injury.

PMID- 15717207
TI  - Characterization of noradrenaline release in the locus coeruleus of freely moving
      awake rats by in vivo microdialysis.
AB  - RATIONALE: The origin and regulation of noradrenaline (NA) in the locus coeruleus
      (LC) is unknown. OBJECTIVES: The neurochemical features of NA overflow (nerve
      impulse dependence, neurotransmitter synthesis, vesicle storage, reuptake, alpha2
      adrenoceptor-mediated regulation) were characterized in the LC. METHODS: Brain
      microdialysis was performed in awake rats. Dialysates were analyzed for NA.
      RESULTS: NA in the LC decreased via local infusion of Ca2+-free medium (-42+/-5%)
      or the sodium channel blocker tetrodotoxine (TTX) (-47+/-8%) but increased (333+/
      40%) via KCl-induced depolarization. The tyrosine hydroxylase (TH) inhibitor
      alpha-methyl-p-tyrosine (250 mg kg(-1), i.p.) and the vesicle depletory drug
      reserpine (5 mg kg(-1), i.p.) decreased NA. Therefore, extracellular NA in the LC
      satisfies the criteria for an impulse flow-dependent vesicular exocytosis of
      neuronal origin. Local perfusion of the alpha2-adrenoceptor agonist clonidine
      (0.1-100 microM) decreased NA (E(max)=-79+/-5%) in the LC, whereas the opposite
      effect (E(max)=268+/-53%) was observed with the alpha2A-adrenoceptor antagonist
      BRL44408 (0.1-100 microM). This suggests a tonic modulation of NA release through
      local alpha2A-adrenoceptors. The selective NA reuptake inhibitor desipramine
      (DMI) (0.1-100 microM) administered into the LC increased NA in the LC
      (E(max)=223+/-40%) and simultaneously decreased NA in the cingulate cortex,
      confirming the modulation exerted by NA in the LC on firing activity of
      noradrenergic cells and on the subsequent NA release in noradrenergic terminals.
      CONCLUSION: Synaptic processes underlying NA release in the LC are similar to
      those in noradrenergic terminal areas. NA in the LC could represent local
      somatodendritic release, but also the presence of neurotransmitter release from
      collateral axon terminals.

PMID- 15717208
TI  - The mGluR5 antagonist MPEP decreases operant ethanol self-administration during
      maintenance and after repeated alcohol deprivations in alcohol-preferring (P)
      rats.
AB  - RATIONALE: Recent research indicates that blockade of mGluR5 modifies the
      reinforcing properties of ethanol. OBJECTIVES: The present studies examined the
      effects of mGluR5 receptor blockade in a genetic model of high ethanol intake,
      the alcohol-preferring (P) rat, on the maintenance of operant ethanol self
      administration. In addition, we determined the effect of 2-methyl-6-(phenylethyl)
      pyridine (MPEP) on the repeated alcohol deprivation effect. METHODS: Twelve male
      (P) rats were trained in experimental sessions to self-administer 10% w/v ethanol
      via a sucrose-fading procedure. After the establishment of operant ethanol self
      administration, subjects were treated with various metabotropic glutamate
      receptor (mGluR) subtype antagonists immediately prior to experimental sessions:
      the mGluR5 antagonist MPEP (1, 3, and 10 mg/kg); the mGluR2--3 antagonist LY
      341495 (1, 3, and 10 mg/kg); and the mGluR1 antagonist CPCCOEt (1, 3, and 10
      mg/kg). After determining the role of mGluR5 in the maintenance of operant
      ethanol self-administration, we examined the role of this receptor in relapse
      following repeated periods of alcohol deprivation by depriving subjects of
      ethanol exposure for three 2-week deprivation periods. RESULTS: The mGluR5
      antagonist MPEP dose-dependently decreased operant ethanol self-administration.
      In addition, rats that received saline immediately prior to repeated alcohol
      deprivation sessions self-administered ethanol at increasing levels that were
      above those achieved in the last operant-conditioning session prior to the
      initial 2-week deprivation period. This repeated alcohol deprivation effect was
      prevented in subjects pretreated with MPEP (10 mg/kg). CONCLUSIONS: These
      findings suggest that mGluR5 receptors may modulate both the maintenance of
      operant ethanol self-administration and abstinence-induced increases in ethanol
      intake.

PMID- 15717210
TI  - The psychopharmacology of impulsive behaviour in rats VIII: effects of
      amphetamine, methylphenidate, and other drugs on responding maintained by a fixed
      consecutive number avoidance schedule.
AB  - RATIONALE: Impulsive behaviour is a component of psychiatric disorders such as
      bipolar disorder, attention deficit hyperactivity disorder (ADHD), or personality
      disorders. Most experimental studies on impulsive behaviour punish impulsive
      choices by loss or delay of reward. In the present study, impulsive behaviour was
      punished by an explicitly aversive stimulus, using a novel fixed consecutive
      number (FCN) schedule of electric shock avoidance. OBJECTIVES: This study was
      conducted to demonstrate stable performance using the FCN avoidance procedure,
      and examine the effects of drugs previously shown to affect impulsive behaviour
      using a conventional FCN schedule. METHODS: First, rats were trained in the
      appetitive FCN procedure. Pressing the right lever in an operant conditioning
      chamber after having pressed the left lever at least six times delivered a food
      pellet (FCN6). Responses on the right lever before completing this ratio resulted
      in a time out and restarted the ratio. The rats were then switched to FCN
      avoidance. Responses on the right lever made before completion of the ratio also
      resulted in food delivery, but were accompanied by an electric shock. RESULTS:
      Chlordiazepoxide (10.0 mg/kg), ethanol (1.0 g/kg), and haloperidol (0.1 mg/kg)
      increased impulsive behaviour by reducing the number of left lever responses made
      before the right lever was pressed. Imipramine (1.0-10.0 mg/kg) and desipramine
      (1.0-10.0 mg/kg) had no effect on impulsive choice. Amphetamine (0.4 and 0.8
      mg/kg) and methylphenidate (6.0 mg/kg) significantly increased the mean chain
      length, and the proportion of very long chains, indicative of reduced
      impulsivity, although this did not improve efficiency. CONCLUSIONS: The increases
      in impulsivity produced by chlordiazepoxide, ethanol, and haloperidol were
      similar to those under appetitive FCN schedules. In contrast, amphetamine and
      methylphenidate, by reducing impulsivity in the FCN avoidance, induced effects
      opposite to those observed in an appetitive FCN procedure. These results suggest
      that the therapeutic actions of stimulants, to reduce impulsive behaviour in
      ADHD, may arise in part by increasing the control of behaviour by aversive
      stimuli.

PMID- 15717211
TI  - Changes in sleep electroencephalogram and nocturnal hormone secretion after
      administration of the antidyskinetic agent sarizotan in healthy young male
      volunteers.
AB  - RATIONALE: Sarizotan is a 5-HT(1A) agonist with high affinity to D(3) and D(4)
      receptors. In animal experiments, the drug shows a strong anti-cataleptic effect
      and suppresses effectively dyskinesias in animal models of L: -dopa-induced
      dyskinesia and of tardive dyskinesia. Data from an open pilot study in patients
      with Parkinson's disease show clear indication of a treatment effect against L: 
      dopa-induced dyskinesia. OBJECTIVE: CNS-active drugs are known to modulate sleep
      electroencephalogram (EEG) and sleep-related hormone secretion. 5-HT(1A) agonists
      suppress rapid-eye movement (REM) sleep and enhance the secretion of ACTH,
      cortisol, prolactin and growth hormone (GH) at daytime. We hypothesised that
      sarizotan shares these effects. Furthermore, we were interested in the influence
      of sarizotan on leptin, which participates in the regulation of the energy
      balance and is enhanced after various psychoactive drugs. METHODS: Ten healthy
      male subjects were investigated twice in a double-blind, placebo-controlled
      crossover design. Sleep EEG and nocturnal hormone secretion of ACTH, cortisol,
      prolactin, GH and leptin were examined after oral administration of either
      placebo or 20 mg of sarizotan at night. RESULTS: After administration of
      sarizotan, a significant reduction of REM sleep and total sleep time in
      conventional sleep EEG and a significant reduction of sigma- and theta-power in
      spectral analysis were observed. The main effect on nocturnal hormone secretion
      was a significant elevation of prolactin and of ACTH in the first half of the
      night. CONCLUSIONS: While REM sleep was suppressed, the endocrine effects of 20
      mg sarizotan at night were weak. Its sleep-endocrine profile is comparable to the
      effects provoked by selective 5-HT reuptake inhibitors.

PMID- 15717212
TI  - Blockade of the mGlu5 receptor decreases basal and stress-induced cortical
      norepinephrine in rodents.
AB  - RATIONALE: Glutamate, the major excitatory neurotransmitter in the brain mediates
      its effects by both ionotropic and metabotropic receptor subtypes. Recently, the
      search for selective ligands for glutamate receptor subtypes has led to the
      discovery of 2-methyl-6-(phenylethynyl)pyridine (MPEP), an antagonist specific
      for metabotropic glutamate receptor 5 (mGlu5). This receptor is highly expressed
      in limbic forebrain regions and is thought to modulate anxiety-related processes.
      The noradrenergic nucleus locus coeruleus (LC) is an important mediator of stress
      responses and dysfunction of this system is implicated in affective disorders
      such as anxiety and depression. OBJECTIVES: We sought to assess the effects of
      mGlu5 receptor antagonists, MPEP and 3-[(2-methyl-1,3-thiazol-4
      yl)ethynyl]pyridine (MTEP) on cortical norepinephrine (NE) levels. METHODS: In
      vivo microdialysis and high-pressure liquid chromatography with electrochemical
      detection (HPLC-ED) were used to assess the effects of mGlu5 antagonism on
      extracellular NE in the frontal cortex, a major terminal field of the LC.
      RESULTS: Blockade of the mGlu5 receptor elicited significant reductions in
      extracellular NE in the frontal cortex. The benzodiazepine diazepam also reduced
      cortical NE. Furthermore, MPEP administration attenuated stress-induced increases
      in extracellular NE. CONCLUSIONS: Taken together, these data show that MPEP and
      MTEP, through their blockade of the mGlu5, reduce extracellular norepinephrine,
      the impact of which may contribute to their anxiolytic actions.

PMID- 15717209
TI  - Predictors and markers of clozapine response.
AB  - RATIONALE: With other atypical antipsychotics now available, having predictors of
      clozapine response would be of considerable value, offering clinicians guidance
      in their decision as to when, and if, a trial of clozapine is warranted.
      OBJECTIVES: The aim was to review existing evidence regarding identified
      predictors and markers of clozapine response. METHODS: Relevant studies were
      identified through PUBMED searches (1975-June 2004) and cross-referencing of
      reviews and included studies. The data were summarized under two main categories:
      clinical (general, neurological, cognitive/neuropsychological, clozapine levels)
      and biological (biochemical, endocrine, genetic, metabolic, morphological,
      dopamine D2 receptor occupancy). 'Reliable' predictors/markers were defined a
      priori as those with support of at least two independent reports that addressed
      overall response, with no contradictory findings to date. 'Potential'
      predictors/markers had the support of a single report that addressed overall
      response and at least one other evaluating treatment outcome but not directly
      addressing response status. RESULTS AND CONCLUSIONS: Higher baseline clinical
      symptoms and functioning in the previous years and low cerebrospinal homovanillic
      acid/5-hydroxyindoleacetic acid levels were identified as reliable. Three
      potential measures were identified: reduction of frontal cortex metabolic
      activity, reduction of caudate volume, and improvement in P50 sensory gating.

PMID- 15717214
TI  - Intraoperative blood transfusion requirement is the main determinant of early
      surgical re-intervention after orthotopic liver transplantation.
AB  - Liver transplantation is the treatment of choice in selected patients with end
      stage liver disease. Postoperative complications often require surgical re
      intervention. This study is a retrospective single-centre study to assess the
      incidence and type of surgical re-intervention during the in-hospital period
      after liver transplantation and to identify predictors of this re-intervention.
      From 1994 to 2002, 231 consecutive adult liver transplantations were performed.
      Re-intervention was classified as biliary, vascular, bleeding, septicaemia, re
      transplantation or as miscellaneous. One hundred and thirty-nine surgical re
      interventions were performed in 79 of 231 patients (34%). Septicaemia (44%) and
      bleeding (27%) were the most frequent indications for re-intervention, followed
      by biliary (10%) re-intervention. Vascular re-intervention, re-transplantation,
      and re-intervention for miscellaneous reasons, were performed in 7% each. Of all
      analysed variables (gender, age, diagnosis, acute liver failure, Child-Pugh
      classification, Karnofsky score, previous abdominal surgery, creatinine
      clearance, prothrombin time, anti-thrombin, platelet count, surgical technique,
      cold ischaemia time, warm ischaemia time, functional anhepatic time, anatomic
      anhepatic time, revascularisation time, year of transplantation, aprotinin
      administration, transfused platelet concentrate, and red blood cell transfusion
      requirements), only the number of transfused red blood cell concentrates (RBCs)
      was identified as a predictor of surgical re-intervention. Median RBC transfusion
      requirement during liver transplantation was 2.9 l (range 0-18.8 l) in the re
      intervention group compared with 1.5 l (range 0-13.4 l) in the non-re
      intervention group (P<0.001). This study revealed intraoperative blood loss as
      the main determinant of early surgical re-intervention after liver
      transplantation and emphasises the need for further attempts to control blood
      loss during liver transplantation.

PMID- 15717213
TI  - Metabotropic glutamate 2 receptor potentiators: receptor modulation, frequency
      dependent synaptic activity, and efficacy in preclinical anxiety and psychosis
      model(s).
AB  - RATIONALE: To increase subtype selectivity and provide a novel means to alter
      receptor function, we discovered and characterization potentiators for the
      metabotropic glutamate 2 receptor (mGlu2). METHODS AND RESULTS: A class of 3
      pyridylmethylsulfonamides (e.g., 3-MPPTS; 2,2,2-trifluoro-N-[3-(2
      methoxyphenoxy)phenyl]-N-(3-pyridinylmethyl)-ethanesulfonamide) were found to be
      potent, subtype-selective potentiators of human and rat mGlu2. The sulfonamides
      increased agonist potency in functional assays but did not displace orthosteric
      radiolabeled antagonist or agonist binding to cloned mGlu2 receptors. Rather, the
      modulators increased the affinity of most of the orthosteric agonists including
      glutamate, DCG-IV (2S,2'R,3'R)-2-(2',3'-dicarboxylcyclopropyl)glycine), and
      LY354740 (1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicaroxylate monohydrate).
      In striatal brain slices, LY354740 inhibited evoked excitatory postsynaptic
      potentials (EPSPs) equally well following either a low- (0.06 Hz) or high (4 Hz)
      frequency stimulation of corticostriatal afferents. In contrast, the mGlu2
      potentiator cyPPTS (2,2,2-trifluoro-N-[3-(cyclopentyloxy)phenyl]-N-(3
      pyridinylmethyl)-ethanesulfonamide) inhibited striatal EPSPs only at higher
      frequencies of stimulation (2 and 4 Hz). Several sulfonamides including 4-MPPTS,
      4-APPES (N-[4-(4-carboxamidophenoxy)phenyl]-N-(3-pyridinylmethyl)
      ethanesulfonamide hydrochloride monohydrate) and/or CBiPES N-[4'-cyano-biphenyl-3
      yl)-N-(3-pyridinylmethyl)-ethanesulfonamide hydrochloride) were tested in mGlu2/3
      agonist-sensitive rodent model(s) of anxiety and psychosis. As seen with
      LY354740, both 4-MPPTS and 4-APPES were efficacious in a rat fear-potentiated
      startle paradigm. Likewise in mice, CBiPES attenuated a stress-induced
      hyperthermia and PCP-induced hyperlocomotor activity. Furthermore, CBiPES
      mediated alteration in PCP-induced hyperlocomotor activity was sensitive to
      mGlu2/3 antagonist pretreatment. CONCLUSIONS: Taken together, the data indicate
      mGlu2 receptor potentiators have a unique use-dependent effect on presynaptic
      glutamate release, and show efficacy in several mGlu2/3-sensitive animal models
      of psychiatric disorders.

PMID- 15717215
TI  - Kidney transplantation from non-heart-beating donors after oxygenated low-flow
      machine perfusion preservation with histidine-tryptophan-ketoglutarate solution.
AB  - The aim of this study was to determine the potential benefit of aerobic machine
      preservation (MP) with non-colloidal histidine-tryptophan-ketoglutarate (HTK)
      solution compared with MP with Belzer machine perfusion solution (MPS) and
      standard cold storage, after marginal kidneys had been obtained from non-heart
      beating donors. Cardiac arrest was electrically induced in anaesthetized German
      landrace pigs (20-25 kg bw). Their kidneys were harvested 40 min thereafter,
      flushed with HTK by gravity of 100 cm H2O via the renal artery and then stored in
      HTK for 18 h at 4 degrees C. Other organs were subjected to oxygenated (pO2>500
      mmHg) hypothermic pulsatile low-flow machine perfusion with HTK or MP with Belzer
      MPS at P(max)=40 mmHg, yielding transrenal flow values of 0.2-0.3 ml/min per g
      with HTK and approximately twice that amount with Belzer MPS. A well-preserved
      vascular endothelium and intact tubular epithelium were documented by electron
      microscopy at the end of perfusion preservation in both solutions as well as
      after cold storage. Concentrations of ATP (in micromoles per gramme) in tissue
      homogenates at the end of perfusion preservation with HTK were 1.18+/-0.12 vs
      0.16+/-0.02 (P<0.05) after simple cold storage and 2.43+/-0.23 after perfusion
      with Belzer MPS, thus documenting a relevant effect of low-flow perfusion on
      tissue oxygenation. Viability of the grafts was followed for 1 week after
      heterotopic transplantation and bilateral nephrectomy in the recipient pigs.
      Machine perfusion with HTK significantly improved cortical microcirculation upon
      early reperfusion in vivo, as well as maximal serum levels of urea and
      creatinine, compared to recipients receiving cold-stored grafts. No differences
      could be found between MP with HTK or Belzer MPS. In conclusion, provision of
      oxygen during storage is possible by low-flow perfusion with HTK as with Belzer
      MPS and apparently improves graft viability after transplantation.

PMID- 15717216
TI  - Isoniazid-related fulminant hepatic failure in a child: assessment of the native
      liver's early regeneration after auxiliary partial orthotopic liver
      transplantation.
AB  - We report the first case of auxiliary partial orthotopic liver transplantation
      (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF)
      with the aim to determine the ability of the native liver (NL) to recover after
      this particular toxic event. A 10-year-old boy with INH-related FHF underwent
      APOLT after left hepatectomy on the NL. Neurological status and liver function
      rapidly improved, but, on postoperative day 22, urgent re-transplantation was
      needed for graft-hepatic artery thrombosis (HAT) and the NL's incapacity to
      sustain adequate liver function. Histological examination of the NL showed signs
      evident of its regeneration, however. In conclusion, though we faced the clinical
      failure of the NL functionally to sustain the patient in the presence of the
      graft HAT 3, weeks after APOLT, such a failure may be interpreted as time
      related. In fact, the histological picture in this particular case may suggest
      the potential for NL recovery after INH-related FHF.

PMID- 15717217
TI  - Outcome of pregnancy after organ transplantation: a retrospective survey in
      Italy.
AB  - The number of women who decide to have a child after organ transplantation has
      increased. We determined the outcomes of 67 pregnancies of women who had
      undergone kidney, liver or heart transplantation. All recipients had been
      maintained on immunosuppressive therapy before and during pregnancy. Pregnancy
      complications at term were observed in 17 out of 67 women (25%), hypertension
      being the most frequent complication (16.17%). Two transplant rejections were
      reported. Sixty-eight infants were delivered (including one pair of twins); five
      women had two pregnancies at term. Twenty-eight miscarriages (29.2%) were
      recorded. Of these 68 babies (including the pair of twins), 40 (58.8%) were born
      at term and 28 (41.2%) before term. The babies were followed-up for 2 months to
      13 years. According to our previous experience, our study shows that patients who
      have undergone organ transplantation can give birth to healthy infants as long as
      they are monitored accurately during pregnancy.

PMID- 15717218
TI  - Successful pregnancy in a liver transplant recipient treated with lamivudine for
      de novo hepatitis B in the graft.
AB  - Pregnancy is often successful after liver transplantation, despite the
      potentially toxic effects of immunosuppressive drug therapy. Liver transplant
      recipients with recurrent hepatitis C or hepatitis B nonetheless appear to be at
      risk of a worse graft function in the event of pregnancy, and antiviral drugs are
      generally contraindicated in pregnancy because of their teratogenic effects. A 33
      year-old woman had undergone liver transplantation for Caroli's disease 6 years
      previously. Two years later the patient experienced de novo HBV hepatitis.
      Lamivudine treatment (100 mg/day) was started and clearance of HBsAg was
      documented 1 year later. Four years after starting antiviral treatment the
      patient became pregnant, despite of the risk of teratogenic effects; lamivudine,
      cyclosporine and azathioprine were not discontinued for risk of break-through
      hepatitis and acute or chronic rejection. The course of gestation was uneventful
      and caesarean section was performed after 36 weeks. The newborn infant was a
      healthy male weighing 3,080 g and measuring 50 cm.

PMID- 15717219
TI  - Successful living-related liver transplantation for familial hypercholesterolemia
      in the Middle East.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic
      disorder resulting in advanced vascular atherosclerosis and premature death,
      primarily from coronary artery disease. The primary defect is a mutation in the
      gene encoding for the plasma LDL receptor located on the short arm of chromosome
      19. Liver transplantation is currently the most effective method of treating this
      disorder. Living-related liver transplantation (LRLT) has become an excellent
      modality for treating children, including those with inherited metabolic
      diseases. In this paper, we describe the first report of a LRLT for familial
      hypercholesterolemia and review FH and the role of liver transplantation.

PMID- 15717220
TI  - Abstracts of the XXXII Annual Meeting of the Arbeitsgemeinschaft Dermatologische
      Forschung (ADF), 3-5 March 2005, Innsbruck, Austria.

PMID- 15717221
TI  - Vascular pathology of the spleen, part II.

PMID- 15717222
TI  - Continuous enrichment culture and molecular monitoring to investigate the
      microbial diversity of thermophiles inhabiting deep-sea hydrothermal ecosystems.
AB  - The microflora developing during a continuous enrichment culture from a
      hydrothermal chimney sample was investigated by molecular methods. The culture
      was performed in a gas-lift bioreactor under anaerobic conditions, at 90 degrees
      C and pH 6.5, on a complex medium containing sulfur as the terminal electron
      acceptor. Archaeal and bacterial diversity was studied. Microorganisms affiliated
      with the genera Pyrococcus, Marinitoga, and Bacillus were detected through DGGE
      analysis of 16S rDNA. Additional sequences phylogenetically related to
      Thermococcus and epsilon-Proteobacteria were detected by cloning and sequencing
      of 16S rDNA from two samples of the enrichment culture. In comparison, the
      sequences retrieved from cloning analysis from an enrichment culture performed in
      a flask (batch condition) using the same culture medium showed that only members
      of the genus Thermococcus were cultivated. Therefore, continuous enrichment
      culture using the gas-lift bioreactor can be considered as an efficient and
      improved method for investigating microbial communities originating from deep-sea
      hydrothermal vents.

PMID- 15717223
TI  - Use of genetically engineered Escherichia coli to monitor ingestion, loss, and
      transfer of bacteria in termites.
AB  - Escherichia coli was transformed with a recombinant plasmid (pEGFP) containing
      the genes for ampicillin resistance and Green Fluorescent Protein (GFP).
      Escherichia coli expressing GFP (E. coli/GFP+) was then fed to workers of the
      termite Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae). The
      transformed bacteria in the termite guts were detected by growing the gut flora
      under selective conditions and then checking the cultures for fluorescence.
      Recombinant plasmids in the termite gut were detected by plasmid extraction with
      subsequent restriction enzyme digest. The presence of the GFP gene in the gut of
      termites fed with E. coli/GFP+ was verified by PCR amplification. Transformed E.
      coli were ingested rapidly when workers fed on filter paper inoculated with E.
      coli/GFP+. After 1 day, 42% of termite guts harbored E. coli/GFP+. Transfer of E.
      coli/GFP+ from donor termites (fed with E. coli/GFP+) to recipients (fed with
      moist filter paper) occurred within 1 day. However, without continuous
      inoculation, termites lost the transformed bacteria within 1 week.

PMID- 15717224
TI  - Isolation, characterization, and heterologous expression of a carboxylesterase of
      Pseudomonas aeruginosa PAO1.
AB  - We purified to homogeneity an intracellular esterase from the opportunistic
      pathogen Pseudomonas aeruginosa PAO1. The enzyme hydrolyzes p-nitrophenyl acetate
      and other acetylated substrates. The N-terminal amino acid sequence was analyzed
      and 11 residues, SEPLILDAPNA, were determined. The corresponding gene PA3859 was
      identified in the P. aeruginosa PAO1 genome as the only gene encoding for a
      protein with this N-terminus. The encoding gene was cloned in Escherichia coli,
      and the recombinant protein expressed and purified to homogeneity. According to
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and
      analytical gel filtration chromatography, the esterase was found to be a monomer
      of approximately 24 kDa. The experimentally determined isoelectric point was 5.2
      and the optimal enzyme activity was at 55 degrees C and at pH 9.0. The esterase
      preferentially hydrolyzed short-chain fatty acids. It is inhibited by
      phenylmethylsulfonyl fluoride (PMSF) but not by ethylendiaminotetraacetic acid
      (EDTA). Native enzyme preparations typically showed a Michaelis constant (K(m))
      and V(max) of 0.43 mM and 12,500 U mg(-1), respectively, using p-nitrophenyl
      acetate as substrate. Homology-based database searches clearly revealed the
      presence of the consensus GXSXG signature motif that is present in the serine
      dependent acylhydrolase protein family.

PMID- 15717225
TI  - Myxobacterial biodiversity in an established oak-hickory forest and a savanna
      restoration site.
AB  - The purpose of this study was to establish the myxobacterial biodiversity of an
      established oak-hickory forest and a savanna restoration site that has been cut
      and subsequently burned on four occasions between 1993 and 1998 in an attempt to
      restore the land to the native savanna ecosystem. Soil and bark samples were
      processed through standard methods specifically for myxobacteria and numbers and
      types of species were recorded for both locations. Species were identified
      through morphology of fruiting bodies, SDS-PAGE of whole cell protein profiles,
      and 16S rRNA gene sequences. Statistical analyses were employed and suggested
      that significantly greater numbers and types of myxobacteria are present on the
      bark of the trees in the established oak-hickory forest than the bark of trees in
      the savanna restoration site, while little difference in numbers and types of
      species were observed between the soil samples of the two locations.

PMID- 15717227
TI  - Changes in fatty acid composition of Chromohalobacter israelensis with varying
      salt concentrations.
AB  - The adaptation of fatty acid composition of Chromohalobacter israelensis, a
      euryhalophilic bacterium, grown at different salt concentrations was studied. C.
      israelensis tolerated NaCl up to concentrations of 20% (w/v) and showed optimal
      growth at 7% (w/v). Major fatty acids of this bacterium were palmitic acid
      (16:0), stearic acid (18:0), palmetoleic acid (16:1cisDelta9), and cis-vaccenic
      acid (18:1Delta11). The salt concentration strongly influenced the fatty acid
      composition. In the presence of sub-optimal salt concentrations, the degree of
      saturation decreased, suggesting the importance of salt in maintaining the
      osmotic balance of the cell with its environment.

PMID- 15717228
TI  - Grouping myxococci (Corallococcus) strains by Matrix-Assisted Laser Desorption
      Ionization Time-of-Flight (MALDI TOF) mass spectrometry: comparison with gene
      sequence phylogenies.
AB  - Nine Corallococcus isolates and three type strains of Corallococcus species were
      characterized by Intact Cell Mass Spectrometry using Matrix Assisted Laser
      Desorption Ionization Time-of-Flight (MALDI-TOF) mass spectrometry. The resulting
      phenetic clustering was compared to the phylogenetic grouping based upon
      sequences of two housekeeping genes. The three dendrograms of relatedness
      resembled each other in that the isolates were highly similar to the type strains
      of Corallococcus exiguus and Corallococcus coralloides, while Corallococcus
      macrosporus and Myxococcus xanthus were more distantly related. While certain
      pairs of organisms were recovered by spectrometry and genes sequence analysis,
      others were detected by two of the three approaches. The degree of similarity
      determined by sequence analysis of the two genes was not higher than that
      revealed by MALDI-TOF analysis. The results show that the spectral profile,
      consisting of about 25 to 45 masses ranging between 2 and 20 kDa, have indeed
      taxonomic significance, confirming literature data that ribosomal proteins and
      certain housekeeping proteins are responsible for the masses obtained. Provided
      the availability of a database of type strains, MALDI-TOF analysis of unknown
      strains appears to be a rapid and inexpensive method to taxonomically cluster
      environmental isolates, expanding the spectrum to strains other than those of
      medical importance predominantly investigated so far.

PMID- 15717229
TI  - Pectinolytic systems of two aerobic sporogenous bacterial strains with high
      activity on pectin.
AB  - Strains Paenibacillus sp. BP-23 and Bacillus sp. BP-7, previously isolated from
      soil from a rice field, secreted high levels of pectinase activity in media
      supplemented with pectin. Production of pectinases in strain Paenibacillus sp. BP
      23 showed catabolite repression, while in Bacillus sp. BP-7 production of pectin
      degrading enzymes was not negatively affected by glucose. The two strains showed
      lyase activities as the predominant pectinases, while hydrolase activity was very
      low. Analysis of Paenibacillus sp. BP-23 in SDS-polyacrylamide gels and zymograms
      showed five pectinase activity bands. The strict requirement of Ca(2+) for lyase
      activity of the strain indicates that correspond to pectate lyases. For Bacillus
      sp. BP-7, zymograms showed four bands of different size. The strain showed a
      Ca(2+) requirement for lyase activity on pectate but not on pectin, indicating
      that the pectinolytic system of Bacillus sp. BP-7 is comprised of pectate lyases
      and pectin lyases. The results show differences in pectin degrading systems
      between the two aerobic sporogenous bacterial strains studied.

PMID- 15717232
TI  - [Does evidence-based surgery harm autonomy in clinical decision making?].
AB  - Evidence-based clinical guidelines in surgery are frequently confronted with
      scepticism by the medical staff, especially because a confinement of free
      decision making in therapy is expected. Considering that medicine is not merely
      natural science, but can as well be comprehended as social science or art,
      evidence-based medicine (EbM) may lead to an oversimplified and rigid
      standardization in medical care ("cook book medicine"). In addition, scientific
      progress might be prevented by inflexible guidelines. However, it is important
      for surgeons to engage in the development of evidence-based guidelines in order
      to put forward their interests, because it is the lack of medical guidelines that
      might threaten free decision making in surgery - by not confronting economical
      pressure with decisive minimal standards in medical care. Therapeutical freedom
      is a substantial principle in medicine, but it should be considered that
      according to occidental tradition, "freedom" is necessarily involving reason and
      conscientiousness.

PMID- 15717233
TI  - [The catalogue of ambulatory sickness benefits -- realistic? Feasible? Put into
      practice?].
AB  - Ambulatory surgery at German hospitals is an underdeveloped field. New legal
      regulations allow contracts between hospitals and insurance companies which will
      improve this situation. Besides the establishment of quality parameters and a
      fixed payment for the operations the contract lists 307 operations which can be
      performed on an outpatient basis. However, only few operations need to be done
      obligatory as ambulatory surgery. This reflects just incompletely what is already
      operated ambulatory outside the hospitals. Due to altered financial structures in
      case of in-patient treatment and because of a decrease of hospital beds, the
      listed operations in the contract may be reviewed and ambulatory surgery at the
      hospitals will increase in the future. The hospitals need to change their
      structure to establish successfully ambulatory surgery within the hospital
      setting. Finally, German patients need to be convinced that operations done on an
      out-patient basis show the same quality standards like procedures under in
      patient conditions.

PMID- 15717234
TI  - [Ambulatory surgery -- requirements of the anaesthetist].
AB  - The requirements of the anaesthetist regarding ambulatory surgery correspond to
      those in surgical procedures in hospital. This applies especially to the
      examination of the patients prior to anaesthesia. Anamnesis and physical
      examination are more important than radiological or laboratory examinations.
      According to jurisdiction in ambulatory surgery a shorter period of time between
      the declaration of consent and the operation is allowed. However, the patient
      must be guaranteed an adequate period of time for consideration. Since regional
      anaesthesia involves more organization and requires more time, general
      anaesthesia with short-acting drugs should be preferred. In observance to the
      recommendations of anaesthesiological associations and institutions both
      personnel and technical equipment should meet hospital standards. In day case
      surgery especially postoperative care must be well planned. This contains the
      prevention of postoperative nausea or vomiting and a sufficient postoperative
      analgesia.

PMID- 15717235
TI  - [Wound infection and infection-promoting factors in breast cancer surgery -- a
      prospective multicenter study on quality control].
AB  - INTRODUCTION: The quality of treatment of cancer of the female breast is
      reflected not only in such parameters as local recurrence rate and survival
      times, but also in the development of surgical complications. Within the
      framework of a study investigating the performance and quality assurance in
      surgical treatment of breast cancer, therefore, the wound infection rate (WIR)
      and factors influencing it were analysed in a large patient population. METHODS:
      In the period between 1.1.2000 and 31.12.2000, 84 surgical departments
      participated in a prospective multicenter study to investigate primary surgery
      for breast cancer. A total of 1 416 patients were recruited to the study, the
      organization and conduction of which was in the hands of the former surgical
      department 1 of the University of Leipzig under the patronage of the East German
      Working Group for Performance and Quality Control in Surgery in cooperation with
      the An Institute for Quality Control in Operative Medicine of the Otto-von
      Guericke University in Magdeburg. In addition to parameters characterizing
      patients, tumors and diagnostic work-up, we also analysed the surgical treatment
      and its possible complications with the aid of a questionnaire. The definition of
      wound infection was based on the criteria of the "Hospital Infection Control
      Practice Advisory Committee". RESULTS: The overall WIR was 4.5 % (n = 65). 21 (32
      %) of the wound infections (WI) were diagnosed exclusively on a clinical basis
      without establishing the responsible pathogens. In 44 (68 %) of the WI, a search
      for the pathogen was undertaken which in 3 cases (7 %) was negative, and in 41
      cases (93 %) positive. 118 (8.3 %) of the patients received perioperative
      antibiotic cover. The following parameters were found to have a significant
      influence on WIR: local drainage, blood transfusion, the time lapse between
      biopsy and definitive surgery, and the size of the primary tumor. DISCUSSION:
      Some of the above factors (transfusion, time lapse, drainage) can be influenced
      by the therapist. The wound infection rate is a marker for treatment quality.

PMID- 15717236
TI  - [Operative treatment in hand infections].
AB  - Bacterial infections in the hand may begin slowly after innocent wounds. They may
      spread rapidly especially following risk wounds. Destruction of anatomical
      structures causes local defects, severe loss of function and septicemia is
      possible. Causes, pathophysiological, clinical signs, and therapeutical
      management are described. It is most important and un-dispensable to have an
      early and exact diagnosis and consistent therapy: immediate radical surgical
      debridement, open wounds, antibiotic treatment, immobilisation and early
      mobilisation are necessary to have good results.

PMID- 15717238
TI  - [Posttraumatic elbow stiffness: planning and technical aspects of arthrolysis].
AB  - Posttraumatic limitation of range of motion in the elbow joint may be of
      extraarticular, intraarticular or mixed origin. If conservative management fails
      to improve elbow motion, arthroscopic arthrolysis, open arthrolysis and
      distraction arthroplasty are available as therapeutic options. Joint distraction
      for gradual lengthening of shortened ligaments and capsules is used to disimpact
      the humero-ulnar articular surface. Under distraction fixator controlled
      mobilization is carried out. The use of transarticular external fixation is
      particularly helpful in cases of subluxation in order to restore joint congruity
      and facilitate postoperative physiotherapy. The postoperative management plays an
      important role in achieving the therapeutic goal.

PMID- 15717237
TI  - [Covering of soft tissue defects of the lower leg with adipo-facial flaps].
AB  - AIM OF THE STUDY: Soft tissue covering on the lower leg is a difficult challenge.
      A plastic surgical method for covering of these soft tissue defects is presented.
      PATIENTS AND METHODS: From May 1997 until May 2003 36 patients were treated using
      neurovascular flaps. Above the sural or the saphenous nerve an adipo-facial flap
      is dissected, rotated into the defect and fixed without tension. Wound closure of
      the donor-site defect is done primarily or by mesh-graft. RESULTS: In 35 cases
      the flap healed without functional impairment. Primary healing was achieved in 30
      patients. In 5 cases partial loss of the skin island was registered, whereby
      subcutaneous tissue remained vital. Revision by mesh-graft transplantation led to
      successful healing in these patients. In only one patient necrosis of the flap
      was seen. CONCLUSION: Neurovascular flaps usually result in reliable and complete
      healing of soft tissue defects of the lower extremity.

PMID- 15717239
TI  - [Geriatric problems in the perioperative management of surgical interventions].
AB  - Improved healthcare and longer life expectancy have led to more and overall,
      healthier older patients. As a consequence, we now see more surgical
      complications attributable to an ever-increasing spectrum of the physiologic
      changes of aging. These include functional decline, psychiatric as well as
      medical co-morbidities, medication effects and peri-operative environmental
      changes. To maintain high patient care standards in geriatric operative patients,
      surgeons face challenges in peri-operative care (co-morbidities), anesthesia
      (intra-operative circulatory depression, cardiac insufficiency and limited organ
      reserve), and intensive care (cardiopulmonary surveillance and delirium). In
      contrast to the normally temporary surgical period, interdisciplinary approaches
      are essential during extended peri-operative, convalescent, rehabilitation and
      follow-up phases of care in the geriatric patient. This will require competency
      in the realm of geriatrics, on behalf of the treating surgeon who, as a result,
      will become increasingly more specialized in the future. This article addresses
      current epidemiology and symptomatology of particular diseases, and as well,
      offers treatment suggestions with explanations of geriatric pathophysiology and
      functional decline from a clinically relevant perspective. This review highlights
      the increased difficulty in treatment of multiple disease processes in the
      elderly as a result of natural decline in function of all organ systems.

PMID- 15717240
TI  - [Laparoscopic versus open appendectomy: which factors influence the decision
      between the surgical techniques?].
AB  - BACKGROUND: Although in hospitals focussing on minimal invasive surgery
      laparoscopic appendectomy (LA) is widely practiced as method of choice in
      patients with acute appendicitis, the decision for the laparoscopic or the
      conventional technique (OA) is usually ensued by individual viewpoints. Aim of
      this prospective observation study was to analyse the decision algorithm for both
      procedures in patients with the presumptive diagnosis "appendicitis". PATIENTS
      AND METHODS: Between January 1996 and July 2001 512 patients with the presumptive
      diagnosis "acute appendicitis" underwent surgery and, assigned by intention-to
      treat, were subdivided in a laparoscopic (I) and a conventional group (II). The
      choice of surgical procedure was analysed with regard to patient characteristics
      (age, gender, comorbidity), severity of appendicitis (clinical manifestation,
      preoperative inflammation signs), surgeon (clinical experience) and daytime
      (during the day, in the evening, at night). Furthermore, the outcome of either
      method was related to postoperative diagnosis, perioperative morbidity,
      analgesia, length of hospital stay and cosmetic results. RESULTS: In group I 265
      patients and in group II 247 patients underwent surgery. Conversion from LA to OA
      was necessary in 6.4 %. Group I consisted of significantly more female (67.9 %
      vs. 45.7 %) and younger patients (21 yrs. vs. 30 yrs.) with less medical history
      as well as minor severity of tissue inflammation and significantly lower
      preoperative serum inflammation parameters (leukocytes (1000/ml): 10.6 +/- 4.3
      vs. 13.5 +/- 4.9; CRP (mg/l): 2.3 +/- 3.3 vs. 5.6 +/- 7.5, I vs. II: p < 0.001).
      In group I more patients underwent surgery during day-time as well as by more
      laparoscopic-experienced surgeons. In the postoperative histopathologic
      evaluation there were significantly fewer cases with complicated appendicitis
      (33.2 % vs. 52.2 %, p < 0.001). Additionally, patients after LA revealed a lower
      postoperative complication rate (9.3 % vs. 18.3 %), length of hospital stay
      (median 3 vs. 4 days) and duration of analgesia (2.1 +/- 1.8 vs. 4.1 +/- 7.1
      days). CONCLUSIONS: Important factors for decision algorithm between a
      laparoscopic or an open appendectomy include severity of appendicitis, gender,
      day-time as well as the surgeon's individual laparoscopic experience. With
      appropriate indication for each technique, both procedures are of equal value in
      the treatment of acute appendicitis. Furthermore the positive patient selection
      for laparoscopic appendectomy contributed to a better postoperative outcome in
      this study.

PMID- 15717241
TI  - [Postamputation phantom limb pain -- comes the solution into view?].
AB  - About 70 % of amputees will suffer from phantom limb pain sooner or later. Nearly
      all of the amputees will feel some phantom sensations. Phantom limb pain not only
      impairs quality of life, but also impedes considerably social rehabilitation.
      Therefore effective strategies of prevention and treatment are urgently required.
      So far, none of the more than 40 treatment methods has proven to be really
      effective. It is to be expected that the latest theories regarding the emergence
      of phantom limb pain, which were developed on the basis of modern neuroimaging
      techniques, will lead to considerable progress. Accordingly the key to success is
      influencing cortical reorganization and preventing or extinguishing a pain
      memory. The demonstrable influence on central activities implicates several
      preventive and therapeutic modalities, i. e. absolute analgesia before amputation
      for a longer period of time and reduction of cortical reorganization by drugs,
      behaviour interventions and/or suggestion.

PMID- 15717242
TI  - [Viral-induced tumours and pre-malignant cutaneous diseases of the perianal
      region].
AB  - HPV-induced tumours and pre-malignant cutaneous diseases of the anal region are
      rare, without the exception of condylomata acuminata. Often imposing like an
      eczema (especially M. Bowen, M. Paget) the danger of mis-interpretation and
      thereby mis-therapy is great, so that they are not seldom diagnosed in the stage
      of malignant degeneration. A comparatively high rate of recurrence is caused by
      primarily insufficient (surgical) therapy, but also by secondary transformation
      of still unchanged dermal areas and by re-infection. Therefore after-care is
      indicated.

PMID- 15717243
TI  - How safe are laparoscopic intracorporeal anastomoses?
AB  - BACKGROUND: A recent German Multicenter Study comprising 3 070 laparoscopic
      colorectal resections indicates that complete intracorporeal anastomoses are
      performed in only 1.8 % cases. The aim of our study was to review and analyse the
      safety of complete intracorpeal anastomosis. METHODS: In a literature survey we
      searched for complete intracorporeal anastomosis with different key words.
      RESULTS: In agreement with the literature, technically demanding hand-sutured
      anastomoses are no common practice. Intracorporeal anastomosis is usually done
      using endoscopic linear stapling devices or a conventional circular stapler by
      performing end-to-end, end-to-side, and side-to-side anastomoses. These
      techniques are more frequently used in the upper than in the lower
      gastrointestinal tract. CONCLUSIONS: The data published so far, however,
      indicates that completely intracorporeal performed anastomoses are safe in the
      hands of laparoscopically experienced surgeons. This technique implies very low
      percentages of postoperative stenoses (0-10 %) and, furthermore, very low
      percentages of postoperative anastomotic leakages (0-8 %).

PMID- 15717244
TI  - Healing characteristics of a new silver-coated, gelatine impregnated vascular
      prosthesis in the porcine model.
AB  - OBJECTIVES: To investigate the intraluminal and extraluminal healing behaviour of
      a new metallic silver coated, gelatine impregnated vascular graft. DESIGN:
      Comparative animal experimental investigation with randomisation of the animals
      to control and experimental groups. MATERIAL AND METHODS: 24 pigs were assigned
      to two control and two experimental groups. The prostheses were interposed in the
      pigs' infrarenal aorta. For the evaluation, macroscopic, histological and
      immunohistochemical criteria were applied. RESULTS: The macroscopic evaluation
      after explantation of the prosthesis revealed similar healing characteristics in
      the control and experimental groups. The microscopic determination of neo-intimal
      thickness showed no significant differences between the groups; nor did the
      immunohistochemical investigations show any significant difference between the
      control group and the silver-coated prosthesis group. CONCLUSIONS: No
      disadvantage of the silver coating in terms of healing and graft patency was
      found. A possible advantage in terms of the antibacterial effect of the silver
      coating must be investigated in the clinical setting.

PMID- 15717245
TI  - [Phytobezoars: case report and review of the literature].
AB  - We report on the case of a 40-year-old woman with a long year history of
      vegetarian lifestyle, who experienced a phytobezoar induced acute abdomen due to
      a mechanic small bowel ileus. After uncomplicated surgical treatment and post-OP
      course the patient could be discharged on post-OP day 10. Beside a description of
      the historical background, relevant diagnostic and therapeutic aspects are
      mentioned as well as a review of the relevant literature.

PMID- 15717246
TI  - [Primary obturator pyomyositis].
AB  - BACKGROUND: The main objective of our work was to draw attention to the possible
      occurrence of a serious and life-threatening illness, primary pyomyositis of the
      obturator muscles in countries with a mild climate, and to establish basic
      diagnostic criteria for the illness, including differential diagnostics, and to
      propose a treatment method. METHODS: The authors describe two cases (a boy of 11
      and a woman aged 47 years) with the occurrence of primary pyomyositis of the
      obturator muscles in the Czech Republic and they focus on the most important
      clinical symptoms and imaging methods necessary for the establishment of the
      diagnosis. RESULTS: Repeated clinical examinations are important for the
      establishment of the diagnosis, particularly the presence of the symptom triad
      (pain in the hip joint, limping, febrile state), positive inflammatory markers
      and, first and foremost, the demonstration of pyomyositis on CT or MR.
      Differential diagnosis must also consider inflammatory diseases of the locomotor
      system (coxitis, sacroiliitis, osteomyelitis), of the digestive tract (Crohn's
      disease, a tumour, an obturator hernia) and of the urogenital system
      (gonorrhoea). CONCLUSION: The therapy of pyomyositis must be initiated in time by
      bed rest and administration of antibiotics and, if an abscess develops, surgical
      intervention is unconditionally necessary, consisting either in percutaneous
      abscess puncture or incision, perfusion, and application of antibiotics. The
      failure to diagnose an abscess of the obturator muscles and late therapy can
      result in serious complications, septic shock and death.

PMID- 15717247
TI  - [Risk factors for community acquired pneumonia (CAP). A systematic review].
AB  - BACKGROUND AND OBJECTIVE: Community acquired pneumonia (CAP) is the most frequent
      mortal infectious disease in the western industrial countries. So far no detailed
      information about incidence, pathogenetic agents, medical service and risk
      factors existed within Germany. This article reviews international studies, which
      identified risk factors for CAP. METHOD: The MEDLINE database search comprised
      743 articles from 1966 to December 2003. Ten published studies analysing risk
      factors for CAP were included in this study. RESULTS: Age, gender, smoking and
      chronic lung diseases ranged among the leading risk factors. Other variables,
      like medication, dangerous substances, alcohol or sociodemographic factors have
      so far been insufficiently proved. CONCLUSION: Comparable data concerning CAP in
      Germany are currently inadequate. In order to improve the data situation, in
      2002, the Community Acquired Pneumonia NETwork (CAPNET) was established. CAPNET
      assembles and soon intends to publish detailed information about incidence and
      risk factors of Community Acquired Pneumonia.

PMID- 15717248
TI  - [Clinical results of intestinal and multivisceral transplantation at the Charite,
      Berlin. A case series].
AB  - BACKGROUND AND OBJECTIVE: Intestinal transplantation (ITx) is the only causal
      therapy of short bowel syndrome (SBS). Long-term survival after ITx has been
      improved significantly during the last years. The experience with ITx at the
      Charite, Campus Virchow Klinikum, are described and discussed. PATIENTS AND
      METHODS: Twelve isolated ITx and one multivisceral transplantation (including
      stomach, pancreatodudenal complex, small intestine, liver, ascending colon, right
      kidney, and adrenal gland) were performed. Mean recipient age was 37.7+/-10.6 yrs
      (median: 35 yrs; range: 27 - 58 yrs; M:F = 8:5). All patients had irreversible
      SBS (0 - 30 cm residual bowel length; mean: 11.8+/-11.4 cm; median: 13 cm).
      RESULTS: 6-months and 1-year patient and graft survival were 85 % (11/13) and 77
      % (10/13), respectively. Reasons for graft loss and patient death were
      necrotizing enterocolitis, severe, muromonab-resistent, acute rejection, and
      graft ischemia due to complex coagulopathy. All other patients had good long-term
      outcome. They received enteral nutrition at six hours after operation and were
      persistently off total parenteral nutrition (TPN) by week two after ITx.
      CONCLUSION: ITx as established in our centre, with 1-year-patient and graft
      survival rates of 77 %, reflects current international standard. ITx is
      complementary to conservative and other operative methods of treating SBS.
      Referral and indication criteria need wider dissemination to prevent life
      threatening complications of TPN.

PMID- 15717249
TI  - [Postalimentary hypoglycaemia in post-gastrectomy late dumping syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 48-year-old patient had been suffering from
      postalimentary hypoglycemias for several months, occurring regularly 2 hours
      after a meal. 5 years before, repeated fundaplications as well as a selective
      proximal vagotomy due to reflux oesophagitis had been performed. INVESTIGATIONS:
      Physical examination revealed no pathological findings. The diurnal blood sugar
      profile with hourly capillary glucose measurement showed a physiological fasting
      glucose homeostasis and two-hour postprandial decrease of blood glucose down to
      20 mg/dl. The oral glucose tolerance test revealed a noticeable insulin secretion
      with a pathologically increased insulin/glucose index. Scintigraphy demonstrated
      an initially delayed, then accelerated gastric emptying as a consequence of the
      selective proximal vagotomy. DIAGNOSIS, TREATMENT AND COURSE: A postalimentary
      hypoglycemia by hypersecretion of insulin in the context of a post-gastrectomy
      late dumping syndrome was diagnosed. A surgical pyloroplasty was not effective.
      In addition to the modification of eating habits, treatment with subcutaneous
      applied octreotide (Sandostatin), a somatostatin-analogue, was initiated.
      CONCLUSIONS: Postalimentary hypoglycemia can be assigned to late dumping syndrome
      in most cases already by ascribed history taking. The correct diagnosis can be
      achieved by an oral glucose tolerance test with measurement of insulin secretion
      and gastric emptying scintigraphy. Beside other therapeutical options the
      treatment with octreotide is a promising alternative with manageable side
      effects.

PMID- 15717250
TI  - [Irritable bowel syndrome].
AB  - Patients with irritable bowel syndrome (IBS) are highly prevalent among subjects
      seeking medical attention at the general practitioner or specialist level. While
      IBS lacks any disease associated excess mortality, this disorders is relevant to
      the affected subjects due to the considerable burden with regard to the symptoms
      and an impaired quality of life. Furthermore, this disease has a substantial
      impact on society due to the economical consequences. In recent years substantial
      progress has been achieved regarding our pathophysiological understanding.
      However, as usual, there has been a substantial delay between the discovery of
      disease mechanisms and its translation into improved patient care. For diagnosing
      IBS standardized criteria have been established (i. e. Rome II- or the DGVS
      criteria). Regarding treatment, life style advice such as avoidance of specific
      nutrients that precipitate or aggravate or the "little psychotherapy" (addressing
      patients concerns and anxiety regarding the symptoms) are considered essential.
      However, the overall response rate is disappointing. Evidence-based
      pharmacological interventions include herbal preparations, spasmolytics, low dose
      tricyclic antidepressants and 5-HT-3-receptor antagonists and 5-HT-4-receptor
      agonists. At present no cure for patients with IBS exists. Thus, all currently
      available treatments target palliation of symptoms. This, however, may change in
      the future.

PMID- 15717251
TI  - [Stent implantation or bypass? Current database in patients with stable coronary
      heart disease].

PMID- 15717252
TI  - [New options for the pharmacotherapy of Alzheimer's disease after the
      registration of memantine?].

PMID- 15717254
TI  - [Lethal polypharmacy in a patient with arterial hypertension--re the article from
      DMW 50/2004].

PMID- 15717255
TI  - Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects.
AB  - Human immunodeficiency virus (HIV)-infected South African patients (n=468)
      received blinded lamivudine or emtricitabine, stavudine, and either nevirapine or
      efavirenz (based on screening viral load). Baseline characteristics were analyzed
      in univariate and multivariate regression, to identify risk factors for
      hepatotoxicity (grade 3 or greater increase in serum aminotransferase levels).
      The occurrence of early hepatotoxicity was 17% in the nevirapine group and 0% in
      the efavirenz group and was balanced between the lamivudine and emtricitabine
      arms. Two subjects died of hepatic failure. Independent risk factors were body
      mass index (BMI) <18.5, female sex, serum albumin level <35 g/L, mean corpuscular
      volume >85 fL, plasma HIV-1 RNA load <20,000 copies/mL, aspartate
      aminotransferase level <75 IU/L, and lactate dehydrogenase level <164 IU/L. The
      use of nevirapine in female patients with a low BMI should be discouraged.

PMID- 15717256
TI  - Simplification therapy with once-daily emtricitabine, didanosine, and efavirenz
      in HIV-1-infected adults with viral suppression receiving a protease inhibitor
      based regimen: a randomized trial.
AB  - BACKGROUND: We assessed a once-daily combination to simplify therapy in patients
      infected with human immunodeficiency virus type 1 (HIV-1). METHODS: A total of
      355 adults with plasma HIV-1 RNA levels <400 copies/mL were randomly assigned to
      either switch to once-daily emtricitabine, didanosine, and efavirenz (n=178) or
      maintain their protease inhibitor (PI)-based regimens (n=177). The primary end
      point was sustained suppression of plasma HIV-1 RNA levels to <400 copies/mL.
      RESULTS: At week 48, the proportion of patients meeting the end point was 87.6%
      in the PI group and 90.5% in the once-daily group, with a treatment difference of
      -2.9% (upper bound of the 1-tailed 95% confidence interval, 2.6%). The proportion
      of patients with HIV-1 RNA levels <50 copies/mL was higher in the once-daily
      group (87%) than in the PI group (79%) (P<.05). Resistance mutations to efavirenz
      and emtricitabine were detected in all patients in the once-daily group who
      experienced virologic failure while receiving study medication. The proportion of
      patients discontinuing study medication because of adverse events was similar
      between the once-daily group (9%) and the PI group (10%) (P=.8). CONCLUSIONS:
      Substituting a convenient once-daily combination of emtricitabine, didanosine,
      and efavirenz for a PI-based regimen was well tolerated and associated with
      sustained virologic suppression.

PMID- 15717257
TI  - Didanosine in HIV-1-infected patients experiencing failure of antiretroviral
      therapy: a randomized placebo-controlled trial.
AB  - BACKGROUND: The antiviral efficacy of didanosine in patients experiencing
      virological failure is not well known. METHODS: A total of 168 patients (139 men
      and 29 women) receiving stable antiretroviral therapy with plasma human
      immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL were
      randomly assigned to have didanosine (n=111) or placebo (n=57) added to their
      currently failing regimen for 4 weeks. The primary efficacy end point was the
      change in HIV-1 RNA level from baseline to week 4. RESULTS: At baseline, the
      median HIV-1 RNA level was 3.8 log(10) copies/mL, the median CD4 cell count was
      378 cells/mm(3), and the median number of nucleoside reverse-transcriptase
      inhibitor-associated mutations (NAMs) was 4. At week 4, a significant decrease in
      the median HIV-1 RNA level was observed in the didanosine group, compared with
      that in the placebo group (-0.56 vs. +0.07 log(10) copies/mL, respectively)
      (P<.0001). A total of 33 patients (31%) in the didanosine group, compared with 3
      (6%) in the placebo group, had HIV-1 RNA levels <400 copies/mL (P<.001).
      Significant antiviral activity of didanosine was observed in patients with up to
      5 NAMs at baseline. Diarrhea occurred in 5 patients (5%) in the didanosine group
      and 2 patients (4%) in the placebo group. CONCLUSIONS: In HIV-1-infected patients
      experiencing failure of antiretroviral therapy, didanosine retains short-term
      antiviral activity.

PMID- 15717258
TI  - Effects of of didanosine-related depletion of mtDNA in human T lymphocytes.
AB  - The normal metabolism of mitochondria in T lymphocytes is unknown, as are the
      effects from nucleoside-analogue reverse-transcriptase inhibitors that impair
      mitochondrial polymerase- gamma . We isolated peripheral-blood CD4 and CD8 T
      lymphocytes from 6 healthy men and stimulated them with anti-CD3 and anti-CD28
      antibodies, in the presence and in the absence of didanosine (ddI). In the
      absence of ddI, mitosis of T lymphocytes was paralleled by a transient up
      regulation of both mtDNA and production of lactate. In CD4 lymphocytes, 10-day
      incubation with ddI at concentrations of 11.8 mu mol/L, 35.4 mu mol/L, 59.0 mu
      mol/L, and 118.0 mu mol/L induced (1) a concentration-dependent reduction of both
      mtDNA (to 73%, 29%, 24%, and 23%, respectively, of the levels in control samples)
      and subunit II of mtDNA-encoded cytochrome c oxidase (to 86%, 81%, 55%, and 31%,
      respectively, of the levels in control samples) and (2) a concentration-dependent
      increase in production of lactate (to 139%, 222%, 276%, and 312%, respectively,
      of the levels in control samples). Activation of lymphocytes (which was measured
      in terms of expression of CD25) was unaffected. Mitochondrial depolarization
      (assessed by staining with JC-1) was observed as early as day 7 of incubation.
      All changes were time dependent and also were observed in isolated CD8
      lymphocytes. Electron microscopy revealed enlarged mitochondria with vacuoles,
      inclusions, and reduced electron density. ddI at a concentration of 11.8 mu mol/L
      induced changes that bordered statistical significance. After stimulation, there
      was a wide range in the change of mtDNA content in lymphocytes. Therefore, mtDNA
      measurements in blood are not necessarily a marker for the mitochondrial toxicity
      of ddI. Nevertheless, ddI does lead to depletion of mtDNA in lymphocytes and to
      functional impairment.

PMID- 15717260
TI  - Epidemiology and predictive factors for chemokine receptor use in HIV-1
      infection.
AB  - BACKGROUND: CXCR4-using virus is associated with higher viral load and
      accelerated human immunodeficiency virus (HIV) disease progression. Additionally,
      CCR5 antagonists may not reduce the HIV-1 RNA load when mixed/dual-tropic or
      CXCR4-using virus is present. The determination of coreceptor tropism may be
      required before CCR5 or CXCR4 antagonists are initiated, unless reliable
      predictive markers of coreceptor use are established. METHODS: Samples from
      treatment-naive and -experienced HIV-1-positive individuals with date-matched CD4
      and CD8 cell counts and HIV-1 RNA, clade, and pol sequences were assessed for
      coreceptor usage, by use of the ViroLogic PhenoSense assay. RESULTS: Coreceptor
      use determination was successful in 563 of 861 samples. Non-clade B virus was
      present in 18.6% of samples. CXCR4 or mixed/dual-tropic CCR5/CXCR4 virus was
      present in 112 of samples (19.9%). Only 4 samples (0.7%) showed exclusive CXCR4
      use. In a multivariate model, higher CD4 cell count, lower viral load, and higher
      natural killer cell counts were significantly associated with CCR5 usage. No
      associations with treatment experience, clade, or pol gene mutations were
      observed. CONCLUSION: The prevalence of CCR5-tropic HIV-1 phenotype declines with
      decreasing CD4 cell count and increasing viral load. Mixed/dual tropic virus is
      found in all CD4 cell count and viral load strata. Coreceptor usage is not
      influenced by viral clade.

PMID- 15717261
TI  - Dynamics of cytomegalovirus (CMV)-specific T cells in HIV-1-infected individuals
      progressing to AIDS with CMV end-organ disease.
AB  - BACKGROUND: Since cytomegalovirus (CMV) infection can cause serious clinical
      complications in immunocompromised individuals, we assessed cellular immune
      requirements for protection against CMV end-organ disease (CMV-EOD) in human
      immunodeficiency virus type 1 (HIV-1) infection. METHODS: Longitudinal samples
      from HIV-1-infected patients in the Amsterdam cohort were analyzed. Dynamics of
      CMV-specific CD8(+) and CD4(+) T cell responses were analyzed by 4-color
      fluorescence analysis using major histocompatibility class I CMV peptide
      tetramers and by intracellular staining for perforin, granzyme B, and interferon
      (IFN)- gamma after stimulation with CMV-specific stimuli. CMV load was measured
      in parallel. RESULTS: In individuals progressing to acquired immunodeficiency
      syndrome with CMV-EOD, CMV-specific IFN- gamma -producing CD4(+) T cells
      disappeared during the year before onset of CMV-EOD. This disappearance was
      accompanied by a sharp increase in CMV load before onset of disease. Despite
      increasing CMV-specific CD8(+) T cell counts, decreasing CMV-specific IFN- gamma 
      producing CD8(+) T cell counts were found over time. In contrast, the percentage
      of CMV-specific perforin- and granzyme B-expressing CD8(+) T cells increased.
      CONCLUSIONS: Our data indicate that insufficient help of CD4(+) T cells may cause
      loss of IFN- gamma -producing CD8(+) T cells and loss of control of CMV
      dissemination. Increasing CMV-infected cell counts in the face of high CMV
      specific perforin- and granzyme B-expressing CD8(+) T cell counts may explain the
      immune pathological characteristics of CMV disease.

PMID- 15717259
TI  - Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: a phase 2
      clinical trial in Uganda.
AB  - Background. Human immunodeficiency virus (HIV)-infected patients with
      tuberculosis (TB) respond to effective antituberculous therapy, but their
      prognosis remains poor. Mounting evidence from clinical studies supports the
      concept of copathogenesis in which immune activation that is triggered by TB and
      mediated by cytokines stimulates viral replication and worsens HIV infection,
      especially when immune function is preserved.Methods. We performed a phase 2,
      randomized, double-blind, placebo-controlled clinical trial in Kampala, Uganda,
      to determine whether immunoadjuvant prednisolone therapy in HIV-infected patients
      with TB who have CD4(+) T cell counts >/=200 cells/ mu L is safe and effective at
      increasing CD4(+) T cell counts.Results. Short-term prednisolone therapy reduced
      levels of immune activation and tended to produce higher CD4(+) T cell counts.
      Although prednisolone therapy was associated with a more rapid clearance of
      Mycobacterium tuberculosis from the sputum, it was also associated with a
      transient increase in HIV RNA levels, which receded when prednisolone therapy was
      discontinued. The intervention worsened underlying hypertension and caused fluid
      retention and hyperglycemia.Conclusion. The benefits of prednisolone therapy on
      immune activation and CD4(+) T cell counts do not outweigh the risks of adverse
      events in HIV-infected patients with TB and preserved immune function.

PMID- 15717262
TI  - Sex-based differences in T lymphocyte responses in HIV-1-seropositive
      individuals.
AB  - Sex-based differences in the levels of human immunodeficiency virus 1 (HIV-1) RNA
      in plasma could be associated with differences in the strength of HIV-1-specific
      CD8(+) T cell responses. CD8(+) effector responses in 18 men and 15 women were
      measured 0-2 years (time A) and 5-7 years (time B) after seroconversion. CD8(+)
      effector responses were seen in 7 (39%) of 18 men and 2 (13%) of 15 women at time
      A (P=.13) and in 12 (67%) of 18 men and 10 (67%) of 15 women at time B (P=.99).
      At time B, the strength of CD8(+) effector responses correlated with the number
      of CD4(+) lymphocytes in women ( rho =-0.68; P=.005) but not in men ( rho =-0.14;
      P=.58). The level of HIV-1 RNA was not associated with the strength of CD8(+)
      effector responses according to sex, but there was a sex-based difference in the
      correlation between the strength of CD8(+) effector response and the number of
      CD4(+) lymphocytes.

PMID- 15717263
TI  - Morphine potentiates HIV-1 gp120-induced neuronal apoptosis.
AB  - To investigate the effect of opiates on human immunodeficiency virus type 1 (HIV
      1)-related neuronal apoptosis, primary human fetal neuronal/glial cell cultures
      were exposed to gp120(IIIB) in the absence and the presence of morphine. Although
      morphine by itself had little effect on neuronal survival, the combination of
      morphine (>/=10(-7) mol/L) and gp120(IIIB) (1 nmol/L) significantly increased
      neuronal apoptosis. The mechanism whereby morphine potentiates gp120(IIIB)
      induced neuronal apoptosis appears to involve activation of the p38 mitogen
      activated protein kinase intracellular signaling pathway and microglial cells
      dispersed within the neuronal/glial cell cultures. These results provide
      additional insight into the molecular basis whereby opiate abuse could promote
      HIV-1-associated dementia.

PMID- 15717264
TI  - HIV-1 chemokine coreceptor utilization in paired cerebrospinal fluid and plasma
      samples: a survey of subjects with viremia.
AB  - BACKGROUND: Chemokine receptors serve as coreceptors for human immunodeficiency
      virus type 1 (HIV-1) entry, influence cell tropism, and may critically determine
      central nervous system infection pathogenesis. Using an in vitro functional entry
      assay, we examined utilization of 2 principal coreceptors in cerebrospinal fluid
      (CSF) and plasma in 46 subjects. METHODS: Paired CSF and plasma samples were
      selected from subjects with a range of CD4 T cell counts. Amplified populations
      of env sequences were characterized as using CCR5 (R5), CXCR4 (X4), or both
      receptors (R5+X4). Individual clones derived from 3 subjects were analyzed for
      viral tropism and phylogeny. RESULTS: CSF and plasma pairs were mainly concordant
      for R5 (36/46) or R5+X4 (5/46) viruses. However, 5 pairs were discordant, 2 of
      which had the R5+X4 phenotype in CSF despite having the R5 phenotype in plasma.
      Although R5+X4 tropism was associated with advanced immunodeficiency, all 4
      subjects with acquired immunodeficiency syndrome dementia complex had R5 tropism
      in CSF. Clones derived from R5+X4-tropic populations revealed mixtures of R5 and
      X4 viruses and viruses able to utilize either coreceptor, suggesting both virus
      exchange between compartments and autonomous CSF virus evolution. CONCLUSIONS:
      Although R5 viruses predominate in the CSF, HIV-1 populations able to utilize
      CXCR4 are also present. Discordant tropism in CSF and plasma may have
      implications for R5 inhibitor therapy.

PMID- 15717265
TI  - Identification of networks of sexually transmitted infection: a molecular,
      geographic, and social network analysis.
AB  - BACKGROUND: Despite widespread efforts to control it, Chlamydia trachomatis
      remains the most frequently diagnosed bacterial sexually transmitted infection
      (STI). Analysis of sexual networks has been proposed as a novel tool for control
      of and research into STI. In the present study, we combine molecular genotype
      data, analysis of geographic clusters, and sociodemographic descriptors to
      facilitate analysis of large sexual networks. METHODS: Individual chlamydia
      genotypes found in Manitoba, Canada, were analyzed to identify geographic
      clusters, and the identified clusters were further characterized by statistical
      analysis of sociodemographic variables. RESULTS: A total of 10 geographic
      clusters of chlamydia-genotype infection were identified. Clusters in Winnipeg
      showed no or little geographic overlap and could be further differentiated on the
      basis of the sociodemographic characteristics of the individuals within a
      cluster. Several clusters in northern Manitoba overlapped geographically but,
      nonetheless, could be differentiated on the basis of the sociodemographic
      characteristics of the infected individuals. CONCLUSIONS: On the basis of results
      of the combined analyses, each geographic cluster appeared to represent a
      relatively distinct transmission network within the larger sexual network. The
      geographic analysis of the molecular data provided a basis for establishment of
      potential epidemiological connections between small groups of unlinked
      individuals. Analytic approaches of the type described here would help to
      decipher the patterns that exist within large social network data sets and would
      be applicable to many types of infectious agents.

PMID- 15717266
TI  - The natural course of Chlamydia trachomatis infection in asymptomatic Colombian
      women: a 5-year follow-up study.
AB  - The natural course of Chlamydia trachomatis infection and its risk factors were
      studied in Colombian women with normal cytological results, during a 5-year
      period. Eighty-two women who were found to be positive for C. trachomatis at the
      start of the study were studied at 6-month intervals. At each visit, a cervical
      scrape sample was obtained for detection of C. trachomatis by use of C.
      trachomatis endogenous-plasmid polymerase chain reaction (PCR)-enzyme immunoassay
      and VD2-PCR-reverse line blot assay. Of the women studied, 67% had a single
      serovar infection, 10% had a mixed-serovar infection, and 23% had an infection
      with an unidentified type. An inversed rate of clearance of C. trachomatis
      infection was observed with oral contraceptive use (hazard ratio [HR], 1.7 [95%
      confidence interval {CI}, 1.1-2.7]) and first sexual intercourse at >/=20 years
      of age (HR, 4.3 [95% CI, 2.3-8.0]). Serovars of group B (B, D, and E) and C (H,
      I, J, and K) had a decreased rate of clearance (rate ratio, 0.4 [95% CI, 0.1
      0.9]), compared with that for serovars of the intermediate group (F and G). At 4
      years of follow-up, 94% of the women had cleared their infections.

PMID- 15717267
TI  - Evaluation of antimicrobial resistance and treatment failures for Chlamydia
      trachomatis: a meeting report.
AB  - Each year, Chlamydia trachomatis causes ~3 million new infections and results in
      more than 1 billion dollars in medical costs in the United States. Repeat or
      persistent infection occurs in 10%-15% of women who are treated for C.
      trachomatis infection. However, the role played by antimicrobial resistance in C.
      trachomatis treatment failures or persistent infection is unclear. With
      researchers in the field, we reviewed current knowledge and available approaches
      for evaluating antimicrobial resistance and potential clinical treatment failures
      for C. trachomatis. We identified key research questions that require further
      investigation. To date, there have been no reports of clinical C. trachomatis
      isolates displaying in vitro homotypic resistance to antimicrobials, but in vitro
      heterotypic resistance in C. trachomatis has been described. Correlation between
      the results of existing in vitro antimicrobial susceptibility tests and clinical
      outcome after treatment for C. trachomatis infection is unknown. Animal models
      may provide insight into chlamydial persistence, since homotypic resistance
      against tetracycline has been described for Chlamydia suis in pigs. Evaluating C.
      trachomatis clinical treatment failures, interpreting laboratory findings, and
      correlating the 2 clearly remain extremely challenging undertakings.

PMID- 15717268
TI  - Factors associated with absence of H2O2-producing Lactobacillus among women with
      bacterial vaginosis.
AB  - BACKGROUND: Women with bacterial vaginosis have different microbiological
      profiles. Our objective was to identify risk factors for an absence of H(2)O(2)
      producing lactobacilli among women with bacterial vaginosis. METHODS: We
      performed a retrospective analysis of 947 women with bacterial vaginosis who were
      enrolled in prospective studies investigating vaginal colonization and genital
      tract infections. RESULTS: Women were categorized into 2 groups: those with
      H(2)O(2)-producing lactobacilli present (n=191; 20.2%) and those with H(2)O(2)
      producing lactobacilli absent (n=756; 79.8%). Multivariate logistic regression
      demonstrated that douching >/=2 times during the past month (odds ratio [OR],
      2.5; 95% confidence interval [CI], 1.1-6.0) and having >/=3 sex partners during
      the past year (OR, 4.5; 95% CI, 1.8-11.7) were predictive of an absence of
      H(2)O(2)-producing lactobacilli. CONCLUSION: Among women with bacterial
      vaginosis, H(2)O(2)-producing lactobacillus colonization is influenced by sexual
      activity and douching habits. These findings may have important implications for
      response to treatment, relapse rate, and risk for sexually-transmitted-disease
      acquisition among women with bacterial vaginosis.

PMID- 15717269
TI  - Bikunin suppresses lipopolysaccharide-induced lethality through down-regulation
      of tumor necrosis factor- alpha and interleukin-1 beta in macrophages.
AB  - BACKGROUND: Lipopolysaccharide (LPS) is the primary mediator of gram-negative
      sepsis; it induces the production of macrophage-derived cytokines. It has been
      shown that bikunin, a Kunitz-type protease inhibitor, inhibits LPS-induced
      cytokine expression. METHODS: To explore the role of bikunin, bikunin knockout
      (Bik(-/-)) mice were used for in vitro cytokine experiments and in vivo animal
      models. RESULTS: We show that a higher level of LPS-mediated death was induced in
      Bik(-/-), compared with wild-type (wt), mice; the administration of bikunin
      caused a significant reduction in LPS-induced lethality; LPS significantly
      increased tumor necrosis factor (TNF)- alpha and interleukin-1 beta levels in
      Bik(-/-), relative to wt, mice after LPS challenge; concomitant administration of
      bikunin inhibited the LPS-induced plasma levels of these cytokines; bikunin
      suppressed the LPS-induced up-regulation of cytokine expression through the
      suppression of the phosphorylation of ERK1/2, JNK, and p38 in macrophages; and
      LPS-induced up-regulation of TNF- alpha expression was not enhanced in Bik(-/-)
      macrophages without endogenous bikunin. CONCLUSIONS: These data allow us to
      speculate that the increased sensitivity of Bik(-/-) mice to LPS-induced death in
      vivo is due to a lack of circulating bikunin in plasma. Bikunin may play a role
      as a potent anti-inflammatory agent.

PMID- 15717271
TI  - Mechanisms by which anaerobic microbiota inhibit the establishment in mice of
      intestinal colonization by vancomycin-resistant Enterococcus.
AB  - We used a mouse model to test the hypothesis that anaerobic microbiota in the
      colon inhibit the establishment of vancomycin-resistant enterococci (VRE)
      colonization by depleting nutrients within cecal contents and limiting the
      association of VRE with the mucus layer. Anaerobic growth of VRE was assessed in
      cecal contents and cecal mucus of mice that had received treatment with
      subcutaneous clindamycin or saline. VRE grew to high concentrations in cecal
      contents of clindamycin-treated mice and in cecal mucus of both groups but not in
      cecal contents of saline-treated mice, unless the cecal contents were autoclaved
      or converted into sterile filtrates. After orogastric inoculation of VRE,
      clindamycin-treated mice acquired high concentrations of VRE within the mucus
      layer, whereas saline-treated mice did not. These results suggest that colonic
      microbiota inhibit VRE by producing inhibitory substances or conditions rather
      than by depleting nutrients. The colonic mucus layer provides a potential niche
      for growth of VRE.

PMID- 15717270
TI  - Bacterial peptidoglycan-associated lipoprotein: a naturally occurring toll-like
      receptor 2 agonist that is shed into serum and has synergy with
      lipopolysaccharide.
AB  - Sepsis is initiated by interactions between microbial products and host
      inflammatory cells. Toll-like receptors (TLRs) are central innate immune
      mediators of sepsis that recognize different components of microorganisms.
      Peptidoglycan-associated lipoprotein (PAL) is a ubiquitous gram-negative
      bacterial outer-membrane protein that is shed by bacteria into the circulation of
      septic animals. We explored the inflammatory effects of purified PAL and of a
      naturally occurring form of PAL that is shed into serum. PAL is released into
      human serum by Escherichia coli bacteria in a form that induces cytokine
      production by macrophages and is tightly associated with lipopolysaccharide
      (LPS). PAL activates inflammation through TLR2. PAL and LPS synergistically
      activate macrophages. These data suggest that PAL may play an important role in
      the pathogenesis of sepsis and imply that physiologically relevant PAL and LPS
      are shed into serum and act in concert to initiate inflammation in sepsis.

PMID- 15717273
TI  - Low seroprevalence of IgG antibodies to Ebola virus in an epidemic zone: Ogooue
      Ivindo region, Northeastern Gabon, 1997.
AB  - A population-based serosurvey was performed to determine the seroprevalence of
      antibodies to Ebola virus (EBO) in a region that has experienced multiple
      epidemics of EBO hemorrhagic fever. Of 2533 residents in 8 villages, serum
      samples from 979 (38.6%) were tested by enzyme-linked immunosorbent assay for
      immunoglobulin (Ig) G and IgM antibodies to Ebola-Zaire (EBO-Z) virus. Fourteen
      samples (1.4%) were found positive for IgG antibodies, and 4 of these (.4%) were
      samples from survivors of an epidemic of EBO hemorrhagic fever. Seroprevalence
      based on the remaining 10 IgG-seropositive individuals with no history of
      exposure to EBO was 1.0% (exact binomial 95% confidence interval, 0.5%-1.9%). No
      serum samples were found positive for IgM antibodies to EBO-Z virus. The low
      seroprevalence suggests that, outside of recognized outbreaks, human exposure to
      EBO in this epidemic zone is rare.

PMID- 15717272
TI  - Hepatitis a molecular epidemiology in the United States, 1996-1997: sources of
      infection and implications of vaccination policy.
AB  - BACKGROUND: The genetic relatedness of hepatitis A virus (HAV) isolates was
      determined to identify possible infection sources for case patients in the
      Sentinel Counties Study of Acute Viral Hepatitis. METHODS: A 315-nucleotide
      segment of the VP1-P2 region of the HAV genome was amplified and sequenced from
      serum of case patients and analyzed together with risk-factor data. RESULTS: Of
      508 HAV-RNA-positive case patients, 449 (88.4%) were interviewed, and 255 (50.1%)
      reported >/=1 risk factor. Some 123 unique nucleotide sequence patterns (UNSPs)
      were identified--77 (62.6%) from only 1 case patient and the rest in 2-99
      persons. Among international travelers, a single person was more often infected
      with a single type of UNSP (17/54 [31.5%]), compared with other case patients
      (48/393 [12.2%]; P<.001). UNSPs from travelers to Mexico (33/37 [89.2%])
      clustered with those from Hispanic children (47/49 [95.9%]). Of 119 men who had
      sex with men, 96 (80.7%) had the same or similar UNSPs, which were also found in
      37 men and 10 women with no identified infection source. CONCLUSION: HAV is often
      transmitted within networks of persons with similar risk factors, which may be
      the infection source for others in the community.

PMID- 15717274
TI  - TNF-alpha promoter polymorphisms and susceptibility to human papillomavirus 16
      associated cervical cancer.
AB  - BACKGROUND: Polymorphisms in the TNF-alpha promoter region have recently been
      shown to be associated with susceptibility to cervical cancer. Some polymorphisms
      have been reported to influence transcription for this cytokine. Altered local
      levels in the cervix may influence an individual's immune response, thereby
      affecting persistence of human papillomavirus (HPV) 16 infection, a primary
      etiological factor for cervical cancer. METHODS AND RESULTS: The association of
      11 TNF-alpha single-nucleotide polymorphisms (SNPs) with susceptibility to HPV16
      associated cervical cancer was investigated. Sequencing of the TNF-alpha promoter
      region confirmed 10 SNPs, and 1 previously unreported SNP (161 bp upstream of the
      transcriptional start site) was discovered. Microsphere-array flow cytometry
      based genotyping was performed on 787 samples from Hispanic and non-Hispanic
      white women (241 from randomly selected control subjects, 205 from HPV16-positive
      control subjects, and 341 from HPV16-positive subjects with cervical cancer). The
      genotype distribution of 3 SNPs (-572, -857, and -863) was significantly
      different between case subjects and control subjects. Analysis of haplotypes,
      which were computationally inferred from genotype data, also revealed
      statistically significant differences in haplotype distribution between case
      subjects and control subjects. CONCLUSIONS: We report new associations between
      several TNF-alpha SNPs and susceptibility to cervical cancer that support the
      involvement of the TNF- alpha promoter region in development of cervical cancer.

PMID- 15717275
TI  - Simultaneous reconstitution of multiple cytomegalovirus-specific CD8+ cell
      populations with divergent functionality in hematopoietic stem-cell transplant
      recipients.
AB  - A panel of 7 human cytomegalovirus (CMV) epitope peptides and corresponding major
      histocompatibility class 1 tetramers was used to evaluate cellular immunity in
      healthy seropositive donors and in hematopoietic stem-cell transplant recipients.
      Broad CMV-specific T cell responses to epitopes were found within several CMV
      polypeptides and were restricted by multiple human leukocyte antigen alleles.
      Their cytotoxic functionality was evaluated by use of an assay that measures
      transient surface levels of lysosomal membrane proteins LAMP-1 (CD107a) and LAMP
      2 (CD107b) after peptide stimulation. This assay can be combined with tetramer
      staining of antigen-specific CD8(+) T lymphocytes and has potential as a
      surrogate marker for cytotoxic function. CD8(+) T lymphocytes specific for
      epitopes within the pp65 or pp50 gene products exhibited significantly higher
      functionality, compared with populations recognizing CMV major immediate early-1
      epitopes. These functional differences between T lymphocyte populations within
      the same individual may have implications for protection against CMV.

PMID- 15717276
TI  - Long-term shedding of infectious epstein-barr virus after infectious
      mononucleosis.
AB  - Epstein-Barr virus (EBV) DNA loads in peripheral blood mononuclear cells (PBMCs),
      plasma, and saliva, as well as infectivity of the virus in saliva, were evaluated
      in 20 patients for 6 months after the onset of infectious mononucleosis (IM). All
      patients displayed sustained high EBV DNA loads in the saliva, associated with a
      persistent infectivity of saliva at day 180. EBV DNA load in PBMCs decreased
      significantly from day 0 to day 180 (in spite of a viral rebound between day 30
      and day 90 in 90% of the patients), and EBV DNA rapidly disappeared from plasma.
      These data show that patients with IM remain highly infectious during
      convalescence.

PMID- 15717277
TI  - Poliovirus-specific memory immunity in seronegative elderly people does not
      protect against virus excretion.
AB  - BACKGROUND: Dutch people born between 1925 and 1945 were ineligible for
      vaccination with the inactivated poliovirus vaccine (IPV) introduced in 1957 and
      may have escaped natural infection because of reduced poliovirus circulation. We
      examined whether people with low or undetectable antibody levels are susceptible
      to infection and whether memory immunity provides protection against virus
      excretion. METHODS: A total of 429 elderly participants were challenged with
      monovalent oral poliovirus vaccine (type 1 or 3) and followed for 8 weeks. Immune
      responses and virus excretion were compared for 4 groups, defined on the basis of
      seronegativity for poliovirus type 1 or 3, natural immunity, and IPV-induced
      immunity. RESULTS: On the basis of the rapidity of the antibody response and the
      absence of immunoglobulin M, we saw clear evidence of memory immune responses in
      33% of the participants without detectable antibodies against poliovirus type 1
      and in 5% of the participants without detectable antibodies against poliovirus
      type 3. Fecal virus-excretion patterns were not significantly different for
      seronegative participants, regardless of whether they showed evidence of memory
      immunity. CONCLUSIONS: Rapid antibody responses after challenge with oral polio
      vaccine provide evidence for poliovirus-specific memory immunity in seronegative
      elderly people. However, in contrast to preexisting immunity, memory immunity
      does not protect against virus excretion. These results have important
      implications for the poliomyelitis-eradication initiative, in particular for
      future immunization policies after eradication has been achieved.

PMID- 15717278
TI  - Cross-serotype neutralization of dengue virus in Aotus nancymae monkeys.
AB  - Previously, we observed that serum from humans immune to dengue serotype 1
      (dengue-1) neutralized the American genotype of dengue serotype 2 (American-2) to
      a greater extent than it neutralized the Asian genotype of dengue serotype 2
      (Asian-2). To determine if this activity is protective, Aotus nancymae monkeys
      were infected with dengue-1 followed by either American-2 or Asian-2. Dengue-1
      infected animals produced antibody with neutralizing titers of 2656 antibodies
      against dengue-1, 409 against American-2, and <20 against Asian-2. Infection with
      American-2 did not produce detectable viremia in either dengue-1-immune or dengue
      1-naive animals. These findings support the hypothesis that dengue-1 immunity
      might have prevented disease or altered the severity of disease in individuals
      sequentially infected with dengue-1 and American-2.

PMID- 15717279
TI  - Clinical and parasitological characteristics of puerperal malaria.
AB  - BACKGROUND: Women with semi-immunity to malaria who live in regions where the
      disease is endemic are at increased risk for more frequent and severe episodes of
      malaria during pregnancy. Recent findings indicate that this increased risk might
      persist beyond delivery, but the underlying mechanisms for this change in risk
      are poorly understood. METHODS: One hundred fifty women were included in a cohort
      study in Lambarene, Gabon, and were actively followed up weekly for 10 weeks
      after delivery, as were nonpregnant control women who had been matched to them by
      location and age. Parasites in samples of placenta and blood were genotyped by
      use of polymerase chain reaction amplification of the merozoite surface antigen 2
      gene and the subtelomeric variable open reading frame gene of Plasmodium
      falciparum. RESULTS: Eleven puerperal women had cases of clinical malaria,
      compared with 1 control woman (rate ratio, 9.8; P=.006). Eighteen puerperal women
      had P. falciparum parasitemia, compared with 6 control women (rate ratio, 2.7;
      P=.03). Five of 16 puerperal women (31%) with parasitemia on follow-up had
      identical parasites in their placentas and blood, and 11 of these cases (69%)
      were the result of reinfection. Puerperal women remained at equal risk for the
      development of parasitemia throughout the first 10 weeks after delivery. Use of
      bed nets, use of chloroquine prophylaxis during pregnancy, presence of malaria
      episodes during pregnancy, gravidity, and age were not associated with the
      acquisition of parasitemia during follow-up. CONCLUSIONS: Compared with
      nonpregnant women, puerperal women have a considerably increased risk for the
      development of malaria and/or parasitemia. This increased risk is caused both by
      the recurrence of P. falciparum parasitemia and by the increased susceptibility
      to new infections, although the latter plays a more significant role.

PMID- 15717280
TI  - Identification of multiple chondroitin sulfate A (CSA)-binding domains in the
      var2CSA gene transcribed in CSA-binding parasites.
AB  - Malaria in pregnancy is a serious complication associated with parasitized
      erythrocyte (PE) sequestration in the placenta. Recent work suggests that var
      genes could play an important role in PE binding to chondroitin sulfate A (CSA),
      a primary placental adherence receptor. Here, we confirm that var2CSA is
      transcriptionally up-regulated in CSA-binding parasites and define CSA-binding
      domains in var2CSA. The identification of multiple binding domains in var2CSA
      strengthens the evidence for their involvement in malaria during pregnancy and
      may have applications for the development of a vaccine against malaria in
      pregnancy.

PMID- 15717281
TI  - In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by
      artemether-lumefantrine (Coartem).
AB  - Artemisinin derivative-based combination therapy is expected to suppress the
      development of Plasmodium falciparum drug resistance in Africa. We have performed
      an artemether-lumefantrine (Coartem; Novartis) follow-up clinical trial in
      Zanzibar, in which pfcrt K76T and pfmdr1 N86Y frequencies were determined before
      drug administration and in all recurrent parasites during a follow-up period of
      42 days. A significant increase in pfmdr1 86N was observed after exposure to the
      drug. This points to 86N as a potential marker of lumefantrine resistance in
      vivo, while suggesting that Coartem is not robust enough to avoid selection of
      resistance-associated mutations in some malarial settings.

PMID- 15717282
TI  - Chemokine receptors of T cells and of B cells in lymphatic filarial infection: a
      role for CCR9 in pathogenesis.
AB  - We examined the expression of chemokine receptors on the surfaces of T cells and
      B cells from 27 individuals either with lymphatic filarial disease (lymphedema),
      with the asymptomatic or subclinical form of filarial infection, or without
      filarial infection. Individuals with lymphedema exhibited increased percentages
      of CCR9-expressing T cells and CCR9-expressing B cells and decreased percentages
      of both CXCR1-and-CXCR3-expressing T cells and CXCR1-and-CXCR3-expressing B
      cells, compared with asymptomatic or uninfected individuals. A significant
      correlation was found between the grade of lymphedema and the percentage of CCR9
      expressing T cells and CCR9-expressing B cells. The percentages of CCR9
      expressing T cells and CCR9-expressing B cells from patients with lymphedema was
      significantly up-regulated in response to live, infective-stage larvae of Brugia
      malayi but not to microfilariae of this parasite. Finally, individuals with
      lymphedema had significantly higher concentrations of interleukin-8, macrophage
      inflammatory protein (MIP)-1alpha , MIP-1beta , monocyte chemotactic protein 1,
      thymus-and-activation-regulated chemokine, and interferon-inducible protein 10 in
      their serum than did uninfected individuals. These results suggest that chemokine
      receptors (particularly CCR9) are involved in the pathogenesis of lymphatic
      filarial disease and that trafficking of particular cellular subsets may
      influence clinical outcome.

PMID- 15717283
TI  - Strongyloidiasis in an HIV-1-infected patient after highly active antiretroviral
      therapy-induced immune restoration.

PMID- 15717285
TI  - Fine mapping of chromosome 17 translocation breakpoints > or = 900 Kb upstream of
      SOX9 in acampomelic campomelic dysplasia and a mild, familial skeletal dysplasia.
AB  - Previously, our group reported a five-generation family in which a balanced
      t(13;17) translocation is associated with a spectrum of skeletal abnormalities,
      including Robin sequence, hypoplastic scapulae, and a missing pair of ribs. Using
      polymerase chain reaction (PCR) with chromosome-specific markers to analyze DBA
      from somatic cell hybrids containing the derivative translocation chromosomes, we
      narrowed the breakpoint on each chromosome. Subsequent sequencing of PCR products
      spanning the breakpoints identified the breaks precisely. The chromosome 17
      breakpoint maps approximately 932 kb upstream of the sex-determining region Y
      (SRY)-related high-mobility group box gene (SOX) within a noncoding transcript
      represented by two IMAGE cDNA clones. A growing number of reports have implicated
      chromosome 17 breakpoints at a distance of up to 1 Mb from SOX9 in some cases of
      campomelic dysplasia (CD). Although this multigeneration family has a disorder
      that shares some features with CD, their phenotype is significantly milder than
      any reported cases of (nonmosaic) CD. Therefore, this case may represent an
      etiologically distinct skeletal dysplasia or may be an extremely mild familial
      example of CD, caused by the most proximal translocation breakpoint from SOX9
      reported to date. In addition, we have refined the breakpoint in a acampomelic CD
      case described elsewhere and have found that it lies approximately 900 kb
      upstream of SOX9.

PMID- 15717287
TI  - Increased first-trimester fetal nuchal translucency thickness in association with
      chondroectodermal dysplasia (Ellis-Van Creveld syndrome).
AB  - Increased nuchal translucency thickness (NT) is an established sonographic marker
      of fetal chromosomal abnormality. Several structural fetal defects and genetic
      syndromes including a range of skeletal dysplasias have been reported in
      association with increased NT. We report the first case of fetal Ellis-Van
      Creveld syndrome presenting as raised fetal NT at 13 weeks' gestation.
      Ultrasonography at 18 weeks' gestation demonstrated a narrow thorax, marked
      shortening of the long bones with bowed femora and hexadactyly of hands and feet.
      Pregnancy was terminated at 23 weeks' gestation. The postmortem radiological
      examination revealed short and bowed long bones with rounded metaphyses,
      postaxial polydactyly of hands and feet, short ribs and narrow thorax. The
      acetabular roofs were horizontal with medial and lateral spurs. This case adds a
      further type of severe skeletal dysplasia to the list of genetic syndromes which
      may present as increased fetal NT in the late first trimester.

PMID- 15717288
TI  - Relationship between cerebroplacental Doppler ratio and birth weight in postdates
      pregnancies.
AB  - OBJECTIVES: To explore the relationship between cerebroplacental Doppler
      impedance index and birth weight in postdates pregnancies, and to evaluate the
      use of a combination of Doppler parameters and ultrasound biometry in the
      prediction of large-for-gestational age (LGA) fetuses at 41 weeks of gestation.
      METHODS: The pulsatility indices of the umbilical (UA-PI) and middle cerebral
      (MCA-PI) arteries, the cerebroplacental pulsatility index ratio (CPR) and the
      estimated fetal weight (EFW) were obtained in a cohort of 181 ultrasound-dated
      pregnancies at 41 weeks' gestation, 2 days before induction of delivery. A
      regression equation was established and the correlation between umbilical artery
      impedance and different birth-weight centile groups was determined. A receiver
      operating characteristics (ROC) curve was used to compare prediction of LGA
      fetuses using biometry alone with that using biometry and UA-PI. RESULTS: UA-PI
      was inversely related to EFW (Spearson's correlation coefficient rho = -0.28, P <
      0.001). Logistic regression showed an independent contribution of UA-PI to the
      birth-weight estimation (birth weight = 1356.8 - 232.0 x UA-PI + 0.65 x EFW). On
      ROC curve analysis, the prediction of LGA with the regression equation was
      comparable to that using ultrasound biometry alone. CONCLUSION: UA-PI was
      inversely correlated to EFW, but the combination of ultrasound biometry and UA-PI
      compared with biometry alone showed similar prediction of LGA fetuses in
      postdates pregnancies. Further prospective trials on larger populations or groups
      with a higher prevalence of LGA fetuses would be needed to validate the use of
      the new formula.

PMID- 15717286
TI  - Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for
      developmental dyslexia.
AB  - Linkage between developmental dyslexia (DD) and chromosome 6p has been replicated
      in a number of independent samples. Recent attempts to identify the gene
      responsible for the linkage have produced inconsistent evidence for association
      of DD with a number of genes in a 575-kb region of chromosome 6p22.2, including
      VMP, DCDC2, KIAA0319, TTRAP, and THEM2. We aimed to identify the specific gene or
      genes involved by performing a systematic, high-density (approximately 2-3-kb
      intervals) linkage disequilibrium screen of these genes in an independent sample,
      incorporating family-based and case-control designs in which dyslexia was defined
      as an extreme representation of reading disability. Using DNA pooling, we first
      observed evidence for association with 17 single-nucleotide polymorphisms (SNPs),
      13 of which were located in the KIAA0319 gene (P<.01-.003). After redundant SNPs
      were excluded, 10 SNPs were individually genotyped in 223 subjects with DD and
      273 controls. Those SNPs that were significant at P</=.05 were next genotyped in
      a semi-independent sample of 143 trios of probands with DD and their parents, to
      control for possible population stratification. Six SNPs showed significant
      evidence of association in both samples (P</=.04-.002), including a SNP
      (rs4504469) in exon 4 of the KIAA0319 gene that changes an amino acid (P=.002;
      odds ratio 1.5). Logistic regression analysis showed that two SNPs (rs4504469 and
      rs6935076) in the KIAA0319 gene best explained DD status. The haplotype composed
      of these two markers was significantly associated with DD (global P=.00001 in the
      case-control sample; P=.02 in trios). This finding was largely driven by
      underrepresentation of the most common haplotype in cases (P=.00003 in the case
      control sample; P=.006 in trios; 1-degree-of-freedom tests). Our data strongly
      implicate KIAA0319 as a susceptibility gene for dyslexia. The gene product is
      expressed in brain, but its specific function is currently unknown.

PMID- 15717289
TI  - Does antenatal identification of small-for-gestational age fetuses significantly
      improve their outcome?
AB  - OBJECTIVES: Most obstetric clinics have a program for the identification of small
      for-gestational age (SGA) fetuses because of the increased risk of fetal
      complications that they present. We have a structured model for the
      identification and follow-up of SGA pregnancies. We aimed to determine whether
      the recognition of SGA antepartum improves fetal outcome. METHODS: All
      pregnancies at Malmo University Hospital from 1990 to 1998 (n = 26 968) were
      reviewed. SGA fetuses identified prior to delivery (n = 681) were compared with
      those not identified (n = 573). Also, all pregnancies with SGA fetuses were
      compared with those appropriate-for-gestational age (AGA) (n = 24 585). The risk
      of serious fetal complications (hypoxic encephalopathy grade 2 or 3, intracranial
      hemorrhage, Apgar score <4 at 5 min, neonatal convulsions, umbilical pH <7.0,
      cerebral palsy, mental retardation, stillbirth, intrapartum or infant death) was
      assessed with cross-tabulation and logistic regression analysis, adjusted for
      gestational age and degree of SGA. RESULTS: When compared with SGA fetuses
      identified before delivery (54%), SGA fetuses not identified before delivery were
      characterized by a four-fold increased risk of adverse fetal outcome (odds ratio,
      4.1; 95% CI, 2.5-6.8). Similarly, compared with AGA fetuses, SGA fetuses were
      associated with a four-fold increased risk of serious fetal complications.
      CONCLUSIONS: A structured antenatal surveillance program for fetuses identified
      as SGA results in a lower risk of adverse fetal outcome, compared with cases of
      SGA fetuses not identified antepartum.

PMID- 15717290
TI  - Association analysis of transcripts from the bipolar susceptibility locus on
      chromosome 4q35, exclusion of a pathogenic role for eight positional candidate
      genes.
AB  - Bipolar affective disorder is a major psychiatric illness with a population
      prevalence of up to 1.6%. The disorder is genetically complex. To date, no
      specific gene or DNA sequence variation that predisposes to the disorder has been
      described, however several susceptibility loci have been proposed through genetic
      linkage analysis. We previously identified one such susceptibility locus on
      chromosome 4q35, and refined the interval harboring this susceptibility gene to a
      size that is amenable to positional cloning. Several independent studies have now
      been described that support the presence of a susceptibility gene at this locus.
      In order to identify candidate genes for testing association with bipolar
      disorder, we previously established a comprehensive transcript map that
      encompasses the chromosome 4q35 susceptibility locus implicated in our linkage
      analysis. In this study, we have selected full-length genes from the transcript
      map and determined the genomic structure of each gene. We identified informative,
      intragenic single nucleotide polymorphisms (SNPs) by screening all exons and
      flanking intron sequences in affected individuals from seven bipolar pedigrees
      that we previously reported as showing evidence for linkage to chromosome 4q35.
      Analysis of these SNPs was then extended to our unrelated bipolar case-control
      cohort to test for association with the disorder. Our data suggests that all
      genes analyzed can be excluded from direct involvement in the disorder. We have
      therefore, excluded approximately half the genes within the chromosome 4q35
      candidate interval from playing a direct pathogenic role in bipolar disorder.

PMID- 15717291
TI  - Support for association between ADHD and two candidate genes: NET1 and DRD1.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common, multifactorial
      disorder with significant genetic contribution. Multiple candidate genes have
      been studied in ADHD, including the norepinephrine transporter (NET1) and
      dopamine D1 receptor (DRD1). NET1 is implicated in ADHD because of the efficacy
      of atomoxetine, a selective noradrenergic reuptake inhibitor, in the treatment of
      ADHD. DRD1 is primarily implicated through mouse models of ADHD. DNA from 163
      ADHD probands, 192 parents, and 129 healthy controls was used to investigate
      possible associations between ADHD and polymorphisms in 12 previously studied
      candidate genes (5-HT1B, 5-HT2A, 5-HT2C, ADRA2A, CHRNA4, COMT, DAT1, DRD1, DRD4,
      DRD5, NET1, and SNAP-25). Analyses included case-control and family-based
      methods, and dimensional measures of behavior, cognition, and anatomic brain
      magnetic resonance imaging (MRI). Of the 12 genes examined, two showed a
      significant association with ADHD. Transmission disequilibrium test (TDT)
      analysis revealed significant association of two NET1 single nucleotide
      polymorphisms (SNPs) with ADHD (P < or = 0.009); case-control analysis revealed
      significant association of two DRD1 SNPs with ADHD (P < or = 0.008). No
      behavioral, cognitive, or brain MRI volume measurement significantly differed
      across NET1 or DRD1 genotypes at an alpha of 0.01. This study provides support
      for an association between ADHD and polymorphisms in both NET1 and DRD1;
      polymorphisms in ten other candidate genes were not associated with ADHD. Because
      family-based and case-control methods gave divergent results, both should be used
      in genetic studies of ADHD.

PMID- 15717293
TI  - Serotonin receptor 2C (HTR2C) and schizophrenia: examination of possible
      medication and genetic influences on expression levels.
AB  - The serotonin receptor 2C (HTR2C) gene is of interest in schizophrenia due to its
      involvement in regulation of dopamine activity in the prefrontal cortex. We have
      previously reported a decreased expression of HTR2C mRNA levels in the prefrontal
      cortex of schizophrenia patients. The variability in mRNA expression levels is
      evaluated here more closely in relation to promoter haplotypes and neuroleptic
      treatment received by the patients. The decrease in HTR2C mRNA was present in
      neuroleptic treated individuals and in patients untreated at death, indicating
      that the lower expression is not a short-term medication effect. Three promoter
      polymorphisms were used to construct haplotypes. No SNP displayed genotypic or
      haplotypic association with the disease. Gene expression of HTR2C was not
      affected by haplotype and the expression decrease in schizophrenia patients was
      similar in all haplotype combinations (diplotypes). We conclude that the decrease
      in HTR2C expression in schizophrenia may be related to the disease mechanism
      rather than to drug treatment. The disease related changes in HTR2C expression
      are not related to the promoter variants typed in our sample, but could be due to
      other regulatory variants or trans-acting factors.

PMID- 15717292
TI  - Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic
      patients: a preliminary report.
AB  - DNA methylation changes could provide a mechanism for DNA plasticity and dynamism
      for short-term adaptation, enabling a type of cell memory to register cellular
      history under different environmental conditions. Some environmental insults may
      also result in pathological methylation with corresponding alteration of gene
      expression patterns. Evidence from several studies has suggested that in
      schizophrenia and bipolar disorder, mRNA of the reelin gene (RELN), which encodes
      a protein necessary for neuronal migration, axonal branching, synaptogenesis, and
      cell signaling, is severely reduced in post-mortem brains. Therefore, we
      investigated the methylation status of the RELN promoter region in schizophrenic
      patients and normal controls as a potential mechanism for down regulation of its
      expression. Ten post-mortem frontal lobe brain samples from male schizophrenic
      patients and normal controls were obtained from the Harvard Brain Tissue
      Resources Center. DNA was extracted using a standard phenol-chloroform DNA
      extraction protocol. To evaluate differences between patients and controls, we
      applied methylation specific PCR (MSP) using primers localized to CpG islands
      flanking a potential cyclic AMP response element (CRE) and a stimulating protein
      1 (SP1) binding site located in the promoter region. For each sample, DNA
      extraction, bisulfite treatment, and MSP were independently repeated at least
      four times to accurately determine the methylation status of the target region.
      Forty-three PCR trials were performed on the test and control samples. MSP
      analysis of the RELN promoter revealed an unmethylated signal in all reactions
      (43 of 43) using DNA from the frontal brain tissue, derived from either the
      schizophrenic patients or normal controls indicating that this region of the RELN
      promoter is predominantly unmethylated. However, we observed a distinct
      methylated signal in 73% of the trials (16 of 22) in schizophrenic patients
      compared with 24% (5 of 21) of controls. Thus, the hypermethylation of the CpG
      islands flanking a CRE and SP1 binding site observed at a significantly higher
      level (t = -5.07, P = 0.001) may provide a mechanism for the decreased RELN
      expression, frequently observed in post-mortem brains of schizophrenic patients.
      We also found an inverse relationship between the level of DNA methylation using
      MSP analysis and the expression of the RELN gene using semi-quantitative RT-PCR.
      Despite the small sample size, these studies indicate that promoter
      hypermethylation of the RELN gene could be a significant contributor in effecting
      epigenetic alterations and provides a molecular basis for the RELN gene
      hypoactivity in schizophrenia. Further studies with a larger sample set would be
      required to validate these preliminary observations.

PMID- 15717294
TI  - Superior verbal ability and nonverbal learning disability in a child with a novel
      17p12p13.1 deletion.
AB  - We report the case of a 10-year-old girl with the karyotype
      46,XX,del(17)(p12p13.1) who presented a remarkable incongruence in higher
      cerebral functioning. Certain language skills were very superior, with reading
      and spelling at a 17-19 year-old level of proficiency. Nonverbal skills, however,
      were mostly below average, executive functioning and socialization were impaired,
      and a diagnosis of "nonverbal learning disability" is applied. We speculate that
      the genes deleted include one or some which code for certain specific categories
      of neural substrate that subserve aspects of visual processing and higher
      functioning, but that no "language loci" have been deleted. The particular
      neuropsychological profile that we describe may assist diagnosis of this
      chromosomal deletion.

PMID- 15717295
TI  - Association analysis of the monoamine oxidase A and B genes with attention
      deficit hyperactivity disorder (ADHD) in an Irish sample: preferential
      transmission of the MAO-A 941G allele to affected children.
AB  - Pharmacological and genetic studies suggest the importance of the dopaminergic,
      serotonergic, and noradrenergic systems in the pathogenesis of attention deficit
      hyperactivity disorder (ADHD). Monoamine oxidases A and B (MAO-A and MAO-B)
      degrade biogenic amines such as dopamine and serotonin and thereby control the
      levels of these neurotransmitters in the central nervous system. We examined four
      polymorphisms in the MAO-A gene (30 bp promoter VNTR, CA microsatellite in intron
      2, 941G/T SNP in exon 8, and A/G SNP in intron 12) as well as two markers in the
      MAO-B gene (CA microsatellite in intron 2 and T/C SNP in intron 13) for
      association with ADHD in an Irish sample of 179 nuclear families. TDT analysis of
      the examined MAO-A markers revealed a significant association of the more active
      MAO-A 941G allele with the disorder (chi2 = 5.1, P = 0.03, OR = 1.7). In
      addition, haplotype analysis revealed a significantly increased transmission of a
      haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6
      repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP (famhap
      global statistic 34.54, P = 0.01) to ADHD cases. No significant distortion in the
      number of transmitted alleles was observed between the two examined MAO-B
      polymorphisms and ADHD. These findings suggest the importance of the 941G/T MAO-A
      polymorphism in the development of ADHD at least in the Irish population.

PMID- 15717297
TI  - Histone deacetylation in epigenetics: an attractive target for anticancer
      therapy.
AB  - The reversible histone acetylation and deacetylation are epigenetic phenomena
      that play critical roles in the modulation of chromatin topology and the
      regulation of gene expression. Aberrant transcription due to altered expression
      or mutation of genes that encode histone acetyltransferase (HAT) or histone
      deacetylase (HDAC) enzymes or their binding partners, has been clearly linked to
      carcinogenesis. The histone deacetylase inhibitors are a new promising class of
      anticancer agents (some of which in clinical trials), that inhibit the
      proliferation of tumor cells in culture and in vivo by inducing cell-cycle
      arrest, terminal differentiation, and/or apoptosis. This report reviews the
      chemistry and the biology of HDACs and HDAC inhibitors, laying particular
      emphasis on agents actually in clinical trials for cancer therapy and on new
      potential anticancer lead compounds more selective and less toxic.

PMID- 15717298
TI  - Assessment of humoral immunity to poliomyelitis, tetanus, hepatitis B, measles,
      rubella, and mumps in children after chemotherapy.

PMID- 15717299
TI  - Assessment of humoral immunity to poliomyelitis, tetanus, hepatitis B, measles,
      rubella, and mumps in children after chemotherapy.

PMID- 15717300
TI  - Anatomical basis of glial cell line-derived neurotrophic factor expression in the
      striatum and related basal ganglia during postnatal development of the rat.
AB  - There is increasing evidence that glial cell line-derived neurotrophic factor
      (GDNF) plays a role as a limiting, striatal target-derived neurotrophic factor
      for dopamine neurons of the substantia nigra pars compacta (SNpc) by regulating
      the magnitude of the first phase of postnatal natural cell death which occurs in
      these neurons. While it has been shown that GDNF mRNA is relatively abundant in
      postnatal striatum, the cellular basis of its expression has been unknown. We
      therefore used nonradioactive in situ hybridization and immunohistochemistry to
      examine the cellular basis of GDNF mRNA and protein expression, respectively, in
      postnatal striatum and related structures. We found that GDNF mRNA is expressed
      within medium-sized striatal neurons. Expression in glia was not observed. At the
      protein level, regionally, GDNF expression in striatum was observed in striosomal
      patches, as previously described. At a cellular level a few neurons were
      observed, but they do not account for the striosomal pattern. This pattern is
      predominantly due to GDNF-positive neuropil. Some of this neuropil arises from
      tyrosine hydroxylase-positive nigro-striatal dopaminergic afferents. Astrocytic
      processes do not appear to contribute to the striosomal pattern. GDNF-positive
      fibers are identified not only within intrinsic striatal neuropil, but also in
      fibers within the major striatal efferent targets: the globus pallidus, the
      entopeduncular nucleus, and the SN pars reticulata. We conclude that during
      normal postnatal development, medium-sized neurons are the principal source of
      GDNF within the striatum.

PMID- 15717301
TI  - Hair cell regeneration in sensory epithelia from the inner ear of a urodele
      amphibian.
AB  - The capacity of urodele amphibians to regenerate a variety of body parts is
      providing insight into mechanisms of tissue regeneration in vertebrates. In this
      study the ability of the newt, Notophthalmus viridescens, to regenerate inner ear
      hair cells in vitro was examined. Intact otic capsules were maintained in
      organotypic culture. Incubation in 2 mM gentamicin for 48 hours resulted in
      ablation of all hair cells from the saccular maculae. Thus, any hair cell
      recovery was not due to repair of damaged hair cells. Immature hair cells were
      subsequently observed at approximately 12 days posttreatment. Their number
      increased over the following 7-14 days to reach approximately 30% of the normal
      number. Following incubation of damaged tissue with bromodeoxyuridine (BrdU),
      labeled nuclei were confined strictly within regions of hair cell loss,
      indicating that supporting cells entered S-phase. Double labeling of tissue with
      two different hair cell markers and three different antibodies to BrdU in various
      combinations, however, all showed that the nuclei of cells that labeled with hair
      cell markers did not label for BrdU. This suggested that the new hair cells were
      not derived from those cells that had undergone mitosis. When mitosis was blocked
      with aphidicolin, new hair cells were still generated. The results suggest that
      direct phenotypic conversion of supporting cells into hair cells without an
      intervening mitotic event is a major mechanism of hair cell regeneration in the
      newt. A similar mechanism has been proposed for the hair cell recovery phenomenon
      observed in the vestibular organs of mammals.

PMID- 15717302
TI  - Sexual dimorphism of vocal control nuclei in budgerigars (Melopsittacus
      undulatus) revealed with Nissl and NADPH-d staining.
AB  - Nissl staining and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH
      d) histochemistry were used to explore the existence of sexual dimorphism in
      vocal control nuclei of adult budgerigars (Melopsittacus undulatus), a parrot
      species capable of lifelong vocal learning. Behavioral studies indicate that
      adult males possess larger vocal repertoires than adult females and learn new
      calls more quickly. The results of the present study show that the volumes of all
      vocal nuclei, as measured using both Nissl-stained and NADPH-d-stained material,
      as well as the total numbers of NADPH-d neurons, were 35-110% greater in males.
      Furthermore, all vocal nuclei exhibit conspicuous NADPH-d staining compared to
      surrounding fields in both adult males and females. Nevertheless, there were no
      significant gender differences in either the intensity of neuropil staining or
      the densities of NADPH-d neurons in vocal nuclei. Moreover NADPH-d neuron somal
      shapes were similar in males and females. Diameters of NADPH-d neurons in vocal
      nuclei were 8.5-32% larger in males than in females. Greater size of NADPH-d
      neuronal somata in males may be a general property of this cell type in
      budgerigars because a similar gender difference was found in a visual nucleus,
      the entopallium, which is not directly associated with the vocal control system
      and does not exhibit sexual dimorphism in total volume or total NADPH-d neuron
      numbers. Taken together, the results of the present study favor the hypothesis
      that superior lifelong vocal learning ability in male budgerigars rests largely
      on larger volumes of vocal control nuclei in males rather than on sexual
      dimorphism in the internal composition of vocal nuclei.

PMID- 15717303
TI  - Organization and regulation of paraventricular nucleus glutamate signaling
      systems: N-methyl-D-aspartate receptors.
AB  - Stress activation of the hypothalamo-pituitary-adrenocortical (HPA) axis is
      mediated in part by glutamatergic neurotransmission. The precise nature of
      glutamate effects on stress-integrative hypothalamic paraventricular nucleus
      (PVN) neurons remains to be determined. Therefore, the current study was designed
      to delineate the organization of glutamate/NMDA receptor systems in the PVN and
      to assess regulation of PVN glutamate receptor subunit expression by chronic
      intermittent stress and glucocorticoids. Immunohistochemical studies verified
      that N-methyl-D-aspartate (NMDA) receptor subunit proteins NR1 and NR2A/2B are
      expressed in the medial parvocellular PVN, indicating the potential for NMDA
      receptor regulation of corticotropin-releasing hormone (CRH) release. Dual-label
      confocal analysis revealed that CRH neurons are apposed by vesicular glutamate
      transporter 2 (VGLUT2)-containing terminals, consistent with glutamatergic
      innervation from hypothalamus and/or brainstem. In situ hybridization analysis
      revealed a significant and selective stress-induced decrease (37%) in NR2B
      subunit mRNA expression in the CRH-containing region of the PVN. No changes were
      observed for NR1 or NR2A mRNAs. In contrast, none of the subunits investigated
      showed altered expression following adrenalectomy with or without low/high-dose
      corticosterone replacement. Thus, the observed stress regulation is likely
      mediated by neurogenic mechanisms in the PVN and upstream stress-transducing
      neurocircuitry. Because a loss of NR2B subunit inclusion in NR receptors would
      likely confer increased Ca(++) conductance and faster deactivation kinetics, the
      stress-induced decrease in NR2B mRNA is consistent with enhanced glutamate
      signaling in the PVN following chronic stress and, perhaps, increased basal HPA
      activity and more rapid and/or more robust HPA responses to stress.

PMID- 15717304
TI  - Evidence for "direct" and "indirect" pathways through the song system basal
      ganglia.
AB  - Song learning in oscine birds relies on a circuit known as the "anterior
      forebrain pathway," which includes a specialized region of the avian basal
      ganglia. This region, area X, is embedded within a telencephalic structure
      considered homologous to the striatum, the input structure of the mammalian basal
      ganglia. Area X has many features in common with the mammalian striatum, yet has
      distinctive traits, including largely aspiny projection neurons that directly
      innervate the thalamus and a cell type that physiologically resembles neurons
      recorded in the mammalian globus pallidus. We have proposed that area X is a
      mixture of striatum and globus pallidus and has the same functional organization
      as circuits in the mammalian basal ganglia. Using electrophysiological and
      anatomical approaches, we found that area X contains a functional analog of the
      "direct" striatopallidothalamic pathway of mammals: axons of the striatal spiny
      neurons make close contacts on the somata and dendrites of pallidal cells. A
      subset of pallidal neurons project directly to the thalamus. Surprisingly, we
      found evidence that many pallidal cells may not project to the thalamus, but
      rather participate in a functional analog of the mammalian "indirect" pathway,
      which may oppose the effects of the direct pathway. Our results deepen our
      understanding of how information flows through area X and provide more support
      for the notion that song learning in oscines employs physiological mechanisms
      similar to basal ganglia-dependent forms of motor learning in mammals.

PMID- 15717305
TI  - Heterogeneity of gamma-aminobutyric acid type A receptors in mitral and tufted
      cells of the rat main olfactory bulb.
AB  - Mitral and tufted cells of the olfactory bulb receive strong gamma-aminobutyric
      acid (GABA)-ergic input and express GABA(A) receptors containing the alpha1 or
      alpha3 subunit. The distribution of these subunits was investigated in rats via
      multiple immunofluorescence and confocal microscopy, by using gephyrin as a
      marker of GABAergic synapses. A prominent immunoreactivity was detected
      throughout the external plexiform layer (EPL) and glomerular layer (GL). However,
      although staining for the alpha1 subunit was uniform throughout the EPL, that of
      the alpha3 subunit was most intense in the outer one-third of this layer. All
      mitral cells were positive for the alpha1 subunit. In contrast, the alpha3
      subunit was restricted to a subpopulation of mitral cells, many of which also
      expressed calretinin. Likewise, external tufted cells could be subdivided into
      distinct groups, either singly labeled for the alpha1 or alpha3 subunit or doubly
      labeled. At the subcellular level, staining for the alpha1 and alpha3 subunits
      was punctate, forming clusters partially colocalized with gephyrin. However, many
      alpha1- and alpha3-positive clusters lacked gephyrin, suggesting the existence of
      either nonsynaptic GABA(A) receptor clusters or synaptic receptors not associated
      with gephyrin. Quantitative analysis of colocalization among the three markers in
      the inner EPL, outer EPL, and GL revealed considerable heterogeneity, suggestive
      of a differential organization of GABA(A) receptor subtypes in the apical and
      basal dendrites of mitral and tufted cells. Together these results reveal a
      complex subunit organization of GABA(A) receptors in the olfactory bulb and
      suggest that mitral and tufted cells participate in different synaptic circuits
      controlled by distinct GABA(A) receptor subtypes.

PMID- 15717306
TI  - Estrogen modulates the sexually dimorphic synaptic connectivity of the
      ventromedial nucleus.
AB  - Neurons in the ventrolateral division of the hypothalamic ventromedial nucleus
      (VMNvl) display a remarkable estrogen-dependent functional and structural
      plasticity, which is likely to be mediated, in part at least, by neuronal
      afferents. The present study was designed to determine whether the number of
      synapses per neuron and the size of individual synapses in the VMNvl vary across
      the estrus cycle and, also, whether they differ between the sexes. To accomplish
      this, the VMNvl of adult female rats at proestrus or diestrus day 1 and of age
      matched male rats was analyzed using electron microscopy. We found that a single
      VMNvl neuron receives around 7,000 synapses during diestrus and approximately
      10,000 during proestrus. This estrus cycle-related variation is accounted for by
      increases in the number of all types of synapses. In males, the number of
      synapses received by each VMNvl neuron is similar to that of diestrus rats
      (approximately 7,500). However, in males the number of axodendritic and
      axospinous synapses is smaller than in proestrus rats, whereas the number of
      axosomatic synapses is higher than in diestrus rats. In addition, we found that
      the size of the postsynaptic densities of axospinous and axosomatic synapses is
      consistently larger in males than in females. Our results show that the synaptic
      organization of the VMNvl is sexually dimorphic, with females having more
      dendritic synapses and males more somatic synapses. They also show that the
      synaptic plasticity induced by estrogen in the VMNvl is characterized by changes
      in the number, but not the size, of the synapses.

PMID- 15717307
TI  - Localization of the Na+-activated K+ channel Slick in the rat central nervous
      system.
AB  - Na+-activated K+ currents (K(Na)) have been reported in multiple neuronal nuclei
      and the properties of K(Na) vary in different cell types. We have described
      previously the distribution of Slack, a Na+-activated K+ channel subunit. Another
      recently cloned Na+-activated K+ channel is Slick, which differs from Slack in
      its rapid activation and its sensitivity to intracellular ATP levels. We now
      report the localization of Slick in the rat central nervous system using in situ
      and immunohistochemical techniques. As for Slack, we find that Slick is widely
      distributed in the brain. Specifically, strong hybridization signals and
      immunoreactivity were found in the brainstem, including auditory neurons such as
      the medial nucleus of the trapezoid body. As has also been shown for Slack, Slick
      is expressed in the olfactory bulb, red nucleus, facial nucleus, pontine nucleus,
      oculomotor nucleus, substantia nigra, deep cerebellar nuclei, vestibular nucleus,
      and the thalamus. Slick mRNA and protein, however, also are found in certain
      neurons that do not express Slack. These neurons include those of the hippocampal
      CA1, CA2, and CA3 regions, the dentate gyrus, supraoptic nucleus, hypothalamus,
      and cortical layers II, III, and V. These data suggest that Slick may function
      independently of Slack in these regions. Computer simulations indicate that Slick
      currents can cause adaptation during prolonged stimuli. Such adaptation allows a
      neuron to respond to high-frequency stimulation with lower-frequency firing that
      remains temporally locked to individual stimuli, a property seen in many auditory
      neurons. Although it is not yet known if Slick and Slack subunits
      heteromultimerize, the existence of two genes that encode K(Na), that are widely
      expressed in the nervous system, with both overlapping and nonoverlapping
      distributions, provides the basis for the reported heterogeneity in the
      properties of K(Na) from various neurons.

PMID- 15717308
TI  - Transitin, a nestin-related intermediate filament, is expressed by neural
      progenitors and can be induced in Muller glia in the chicken retina.
AB  - The purpose of this study was to test whether transitin, the avian homologue of
      nestin, is expressed by retinal progenitors in the developing and postnatal
      chicken. Because nestin has been widely used as a cell-distinguishing marker of
      neural progenitors in the mammalian nervous system, we expected to find transitin
      expressed specifically by the neural progenitors of the retina. In early stages
      of development, transitin is expressed by neural progenitors in the retina and by
      cells in the developing ciliary body. During later stages of development,
      transitin expression persists in differentiating Muller glia but is down
      regulated by these cells as maturation proceeds. In the postnatal chick,
      transitin expression is restricted to neural progenitors at the peripheral edge
      of the retina. We found that the expression of transitin in mature Muller glia
      was induced by intraocular injections of insulin and fibroblast growth factor-2
      (FGF2) but not by ciliary neurotrophic factor. In response to insulin and FGF2,
      the expression of transitin was induced in the nonpigmented epithelium (NPE) of
      the ciliary body. In the postnatal retina, acute retinal damage transiently
      induces transitin expression in Muller glia. We propose that the expression of
      transitin by retinal Muller glia and NPE cells in the postnatal animal represents
      a state of de-differentiation and a step toward becoming neurogenic progenitor
      cells. Taken together, our findings indicate that transitin is expressed by
      neural progenitors in the embryonic and postnatal chicken retina. However,
      transitin is not exclusively expressed by neural progenitors and is also
      expressed by non-neurogenic cells.

PMID- 15717309
TI  - Estrogen receptor-beta, but not estrogen receptor-alpha, is expressed in
      prolactin neurons of the female rat paraventricular and supraoptic nuclei:
      comparison with other neuropeptides.
AB  - Estrogen receptor-alpha (ER-alpha) and ER-beta exhibit fine differences in their
      distributions in the rodent forebrain, and one such difference is observed in the
      paraventricular (PVN) and supraoptic (SON) nuclei. To investigate the functional
      significance of ER in these brain areas, we examined the neuropeptide
      characteristics of ER-expressing neurons in the PVN and SON of female rats by
      using dual-label immunocytochemistry. The distributions of ER-alpha
      immunoreactivity (ir) and ER-beta ir were nonoverlapping in the PVN and SON.
      Nuclear ER-alpha ir was found in a population of thyrotropin-releasing hormone
      (TRH)-expressing neurons in the PVN (5.93% +/- 1.20% SEM), but not in any other
      identified cell phenotype of the PVN and SON. The phenotype of neurons with the
      highest percentage expressing ER-beta was found to be prolactin (PRL)
      immunoreactive in both the parvocellular (84.95% +/- 4.11%) and the magnocellular
      (84.76% +/- 3.40%) parts of the PVN as well as the SON (87.57% +/- 4.64%).
      Similarly, most vasopressin-immunoreactive neurons were also ER-beta positive in
      the PVN (66.14% +/- 2.47%) and SON (72.42% +/- 4.51%). In contrast, although a
      high percentage of oxytocin (OXY) neurons coexpressed ER-beta in the PVN (84.39%
      +/- 2.99%), there was very little ER-beta/OXY colocalization in the SON. Low
      levels of corticotropin-releasing hormone neurons also expressed ER-beta ir in
      the PVN (12.57% +/- 1.99%), but there was no ER-beta colocalization with TRH. In
      summary, these findings further support the possibility of direct effects of
      estrogen on neuropeptide expression and implicate estrogen involvement in the
      regulation of various aspects of neuroendocrine function.

PMID- 15717310
TI  - Loss of heterozygosity on chromosome 2 in Japanese patients with prostate cancer.
AB  - BACKGROUND: Loss of heterozygosity (LOH) on chromosome 2 is thought to occur only
      occasionally in prostate cancer (PCa), but allelic losses in this region are
      frequent in other types of human cancer, such as lung, thyroid, head and neck,
      and cervix. Here, we show a high-resolution deletion map of markers on chromosome
      2 in Japanese patients with PCa. METHODS: Tissue samples were obtained from 66
      patients with PCa. DNA from normal, tumor, or metastatic tissue was used as the
      template for polymerase chain reaction amplification for LOH using 24
      microsatellite markers on human chromosome 2. RESULTS: Nineteen of the 66 cases
      (29%) showed LOH for at least one locus on chromosome 2. LOH on 2p was observed
      more frequently in cancer death cases than in organ confined and regional
      diseases (P < 0.001). Paired DNAs were available from both primary and metastatic
      tumors in the eight cases of cancer death; among those pairs, we detected LOH on
      2p in four primary tumors, and in all metastatic foci (P < 0.05). Detailed
      deletion mapping in these tumors identified four distinct commonly deleted
      regions on 2p 16.3, 2p 12-cent, 2q 21.3, and 2q 23.1-2q 32.1. CONCLUSIONS: These
      results suggest that inactivation of putative tumor suppressor genes on
      chromosome 2 that may play an important role in the progression of Japanese
      patients with PCa.

PMID- 15717311
TI  - Sequence variation within the 5' regulatory regions of the vitamin D binding
      protein and receptor genes and prostate cancer risk.
AB  - BACKGROUND: The vitamin D receptor (VDR) and binding protein (DBP) mediate the
      cellular transport, activity, and anti-tumor action of 1,25-dihydroxyvitamin D3
      [1,25-(OH)(2)D3]. The purpose of this investigation is to determine whether novel
      single nucleotide polymorphisms (SNPs) within the transcriptional regulatory
      regions of the VDR and DBP are associated with prostate cancer risk. METHODS:
      Novel SNPs were identified in the VDR and DBP transcription regulatory gene
      regions and genotyped in a case-control study using male subjects with (n=258) or
      without (n=434) prostate cancer. RESULTS: African-American men who possessed at
      least one variant VDR-5132 C allele had a increased risk of prostate cancer
      (OR=1.83; 95% CI: 1.02, 3.31). Further study revealed that the VDR-5132 T/C SNP
      eliminates a GATA-1 transcription factor-binding site. CONCLUSION: The VDR-5132
      T/C SNP, resulting in potential elimination of the GATA-1 transcription factor
      binding site, may increase prostate cancer susceptibility in African-Americans.
      Confirmation of these findings is needed in larger observational studies.

PMID- 15717312
TI  - Acetylation genotype and the genetic susceptibility to prostate cancer in a
      southern European population.
AB  - BACKGROUND: Epidemiologic studies have suggested that environmental factors and
      diet are important risk factors in the pathogenesis of prostate cancer. The N
      acetyltransferases (NAT) are important enzymes in activation and inactivation of
      various carcinogens, including those found in well-cooked meat and cigarette
      smoke. METHODS: We analyzed DNA samples from 146 prostate cancer patients and 174
      healthy men. We used PCR-RFLP method to analyze NAT 1 and NAT 2 polymorphisms.
      RESULTS: We did not find statistically significant differences in NAT 1 genotypes
      frequencies between prostate cancer patients and control group. We observed an
      association of the slow acetylator genotype, NAT 2*6/NAT2*6 with prostate cancer
      protection (P=0.017; OR=0.31, 95% CI 0.11--0.84). Multivariate logistic
      regression analysis confirmed this association (0.030; OR=0.32, 95% CI 0.12-
      0.89). CONCLUSIONS: Our results indicate a role of NAT2 polymorphisms in the
      carcinogenic pathway of prostate cancer, specifically in a population of Southern
      Europe.

PMID- 15717313
TI  - Negative acting HLH proteins Id 1, Id 2, Id 3, and Id 4 are expressed in prostate
      epithelial cells.
AB  - BACKGROUND: The four known Id proteins, Id 1, Id 2, Id 3, and Id 4 are largely
      considered as dominant negative helix-loop-helix (HLH) proteins. They can
      dimerize with basic helix loop proteins (bHLH) but the dimers fail to bind the
      consensus E box response element (CANNTG). Alternatively, members of the Id
      family, for example, Id 2 can also bind to non-bHLH proteins such as
      retinoblastoma (Rb) and ETS-TCF to modulate their activities. Consistent with
      their role as promoters of proliferation, subset of Id genes for example, Id 1
      and Id 2 are expressed in many cancers including that of the prostate. However,
      their expression and function in the normal prostate is unknown. METHODS: The
      present study was designed to evaluate the expression profile and functional
      significance of all Id isoforms in normal rat prostate epithelial cells. The data
      suggests that all four Id isoforms are expressed in normal cells, albeit at
      different levels. RESULTS: Agents that promote growth, for example, serum
      increase the levels of Id 1, Id 2, and Id 3. The hormones and mitogens such as
      testosterone and hepatocyte growth factor (HGF) that promote prostate epithelial
      cell differentiation stimulate Id 4 and Id 2, respectively. CONCLUSIONS: In
      prostate epithelial cells, Id 1 may be specifically involved in promoting
      proliferation whereas Id 4 and Id 2 may have defined roles in regulating
      differentiated functions in response to androgens and local paracrine factors
      such as HGF.

PMID- 15717314
TI  - Changes in intracellular sodium, chlorine, and potassium concentrations in
      staurosporine-induced apoptosis.
AB  - Ion gradients across the plasma membrane, fundamentally K(+), play a pivotal role
      in the execution phase of apoptosis. However, little is known about other
      monovalent anions (Cl(-)) or cations (Na(+)) in apoptosis. In addition, the
      relationship between changes in total ion composition and morphological and
      biochemical events are poorly understood. We investigated simultaneous changes in
      sodium (Na), chlorine (Cl), and potassium (K) concentrations in stauroporine
      induced apoptosis by quantitative electron probe X-ray microanalysis (EPXMA) in
      single cells. Apoptotic cells identified unequivocally from the presence of
      chromatin condensation in backscattered electron images were characterized by an
      increase in intracellular Na, a decrease in intracellular Cl and K
      concentrations, and a decrease in K/Na ratio. The ouabain-sensitive Rb-uptake
      assay demonstrated a net decrease in Na(+)/K(+)-ATPase activity, suggesting that
      increases in Na and decreases in K and the K/Na ratio in apoptotic cells were
      related with inhibition of the Na(+)/K(+)-ATPase pump. These changes in
      diffusible elements were associated with externalization of phosphatidyl serine
      and oligonucleosomal fragmentation of DNA. This alteration in ion homeostasis and
      morphological hallmarks of apoptosis occur in cells that have lost their inner
      mitochondrial transmembrane potential and before the plasma membrane becomes
      permeable.

PMID- 15717315
TI  - Estradiol and cognition during androgen deprivation in men with prostate
      carcinoma.
AB  - BACKGROUND: The adverse effects of hormonal manipulation in prostate carcinoma
      need to be established in view of its increasing use as an adjuvant treatment.
      This prospective study investigated the association of androgen deprivation
      induced estradiol decline with cognition in prostate carcinoma. METHODS:
      Cognitive testing of prostate carcinoma patients was carried out at baseline and
      at 6 and 12 months on androgen deprivation (AD). Cognitive performances were
      evaluated with standardized measures of information processing, including working
      memory and attention, visual and verbal skills, and memory performances in 31
      tests. Testosterone and estradiol changes during AD were measured with the DELFIA
      (PerkinElmer, Inc., Wellesley, MA) system. Associations between changes in
      cognitive performances and estradiol decline were studied. RESULTS: Cognitive
      performances, which were significantly associated with decline in estradiol,
      included visual memory of figures (r = -0.52; P = 0.022) and recognition speed of
      numbers, which were impaired, (r = -0.57; P = 0.030) at 6 months, and improvement
      in verbal fluency (r = -0.52; P = 0.019) at 12 months. Other cognitive domains
      appeared unaffected by estradiol decline. The character of change (impairment or
      improvement) depended on the magnitude of estradiol decline. CONCLUSIONS: The
      cognitive domains of verbal fluency, visual recognition, and visual memory were
      associated with decline in estradiol during androgen deprivation. The results
      suggest selective associations among testosterone decline, estradiol, and
      cognitive performance. Documentation of these associations has implications for
      informed patient support in hormonally treated prostate carcinoma.

PMID- 15717316
TI  - Intracellular domain of the IFNaR2 interferon receptor subunit mediates
      transcription via Stat2.
AB  - We recently demonstrated that IFNaR2, a subunit of the interferon receptor, can
      be proteolytically cleaved in response to interferon-alpha and other activators
      of protein kinase C. Cleavage occurs at multiple sites, via a mechanism similar
      to that employed by Notch and the Alzheimer's precursor protein, and releases the
      intracellular domain (ICD). In this study, we demonstrate that the IFNaR2 ICD,
      when fused to the yeast Gal4 DNA binding domain (Gal4DBD) selectively modulates
      transcription of four different promoters under the control of Gal4 upstream
      activating sequences. We previously showed that Stat2 binds constitutively to the
      ICD of IFNaR2, in a manner that is independent of tyrosine phosphorylation. Here,
      we show that ICD transcriptional modulation is dependent upon the carboxyl
      terminal transactivation domain of Stat2. Specifically, complementing Stat2
      deficient cells with wild-type Stat2 restored the ICD-mediated transcriptional
      effects while complementation with a mutant form of Stat2 lacking the
      transcriptional activation domain (TAD) did not. In addition, mutation of the
      Stat2 binding site on the ICD reduced the transcriptional activity of the Gal4DBD
      ICD. Finally, we demonstrate that the activity of Jak1, a tyrosine kinase also
      known to bind to IFNaR2, is required for ICD-mediated transcriptional effects.

PMID- 15717317
TI  - Glutathione S-transferases in the adaptation to plant secondary metabolites in
      the Myzus persicae aphid.
AB  - Glutathione S-transferases (GST) in insects play an important role in the
      detoxification of many substances including allelochemicals from plants.
      Induction of GST activity in Myzus persicae in response to secondary metabolites
      from Brassica plants was determined using different host plant species and
      confirmed using artificial diet with pure allelochemicals added. The 2,4-dinitro
      1-iodobenzene (DNIB) was found to be a useful substrate for identifying
      particular GSTs in insects. GSTs from M. persicae were purified using different
      affinity chromatography columns and related kinetic parameters were calculated.
      GST isoenzymes were characterised using electrophoretic methods. Although SDS
      PAGE results indicated similarity among the purified enzymes from each affinity
      column, biochemical studies indicated significant differences in kinetic
      parameters. Finally, the GST pattern of M. persicae was discussed in terms of
      insect adaptation to the presence of plant secondary substances such as the
      glucosinolates and the isothiocyanates, from Brassicaceae host plants.

PMID- 15717318
TI  - Identification and expression of odorant-binding proteins of the malaria-carrying
      mosquitoes Anopheles gambiae and Anopheles arabiensis.
AB  - Host preference and blood feeding are restricted to female mosquitoes. Olfaction
      plays a major role in host-seeking behaviour, which is likely to be associated
      with a subset of mosquito olfactory genes. Proteins involved in olfaction include
      the odorant receptors (ORs) and the odorant-binding proteins (OBPs). OBPs are
      thought to function as a carrier within insect antennae for transporting odours
      to the olfactory receptors. Here we report the annotation of 32 genes encoding
      putative OBPs in the malaria mosquito Anopheles gambiae and their tissue-specific
      expression in two mosquito species of the Anopheles complex; a highly
      anthropophilic species An. gambiae sensu stricto and an opportunistic, but more
      zoophilic species, An. arabiensis. RT-PCR shows that some of the genes are
      expressed mainly in head tissue and a subset of these show highest expression in
      female heads. One of the genes (agCP1588) which has not been identified as an
      OBP, has a high similarity (40%) to the Drosophila pheromone-binding protein 4
      (PBPRP4) and is only expressed in heads of both An. gambiae and An. arabiensis,
      and at higher levels in female heads. Two genes (agCP3071 and agCP15554) are
      expressed only in female heads and agC15554 also shows higher expression levels
      in An. gambiae. The expression profiles of the genes in the two members of the
      Anopheles complex provides the first step towards further molecular analysis of
      the mosquito olfactory apparatus.

PMID- 15717319
TI  - Action of 24-epibrassinolide on a cell line of the beet armyworm, Spodoptera
      exigua.
AB  - The Spodoptera exigua cell line Se4 is sensitive for ecdysteroid activity
      stimulated by the insect molting hormone, 20-hydroxyecdysone (20E), showing a
      cease in cell proliferation (with 50% inhibition around 1 microM) and
      characteristic cell morphology changes with aggregation and formation of long
      filamentous cytoplasmic extensions. The bisacylhydrazine tebufenozide also
      triggered such typical cellular effects in Se4, and in addition, it showed an
      affinity for binding in competition with 3H-ponasterone A (PoA) that was similar
      to 20E (with 50% competition around 1 microM), confirming that such non
      ecdysteroids display an ecdysteroid agonist activity. In contrast, when Se4 cells
      were incubated with the native plant hormone 24-epibrassinolide (24BR), none of
      the effects triggered by 20E were observed. Hence, a competition binding
      experiment with 3H-PoA demonstrated no affinity of 24BR for binding to the
      ecdysteroid receptor in the Se4 cell line. In another series of experiments, the
      Se4 cell line was tested in sensitivity response to increased
      acetylcholinesterase (AchE) activity after treatment with ecdysteroid active
      compounds. The AchE activity measured in the cell line is discussed in relation
      to inhibition by eserine. The obtained results suggest that 24BR exerted no
      ecdysteroid activity.

PMID- 15717320
TI  - Immunological assessment of an insecticide resistance-associated esterase in the
      Western corn rootworm.
AB  - In previous investigations, we have determined that organophosphate resistance in
      the western corn rootworm, Diabrotica virgifera virgifera, is at least partially
      attributed to a group of non-specific carboxylesterases referred to as group II.
      Antiserum raised against a purified 66-kDa group II esterase is specific for the
      denatured enzyme. This antiserum reacts similarly with both beetle homogenates
      from resistant and susceptible populations, although there is much higher signal
      intensity in immunoblots of resistant relative to susceptible beetles. These
      results suggest that overproduction of group II esterases is the underlying basis
      of esterase-mediated resistance in D. v. virgifera by demonstrating that (1)
      group II esterases are immunologically indistinguishable between the resistant
      and susceptible populations, and (2) the intensity differences are due to
      increased group II esterase proteins in the resistant population. The diagnostic
      potential of immunological-based assays was tested with a traditional diagnostic
      concentration bioassay and a biochemical-based native PAGE assay. Significant
      correlations were observed among all three diagnostic assays (regression
      coefficients ranging from 0.95 to 0.96). These results demonstrate the importance
      of the 66-kDa protein as a resistance-associated biochemical marker, thus
      emphasizing the potential for 66-kDa protein-targeted immunoassays in resistance
      monitoring programs.

PMID- 15717321
TI  - Detection of bladder carcinoma by combined testing of urine for hyaluronidase and
      cytokeratin 20 RNAs.
AB  - BACKGROUND: A new, sensitive, noninvasive method for the detection of urothelial
      carcinomas of the urinary bladder would open new possibilities in both the
      diagnosis and followup of patients. METHODS: This study included 228 patients
      diagnosed with bladder carcinoma, 68 patients with benign bladder lesions, and 44
      healthy persons served as the control group. All were subjected to: serologic
      schistosomiasis antibody assay in serum, urine cytology, estimation of urine
      hyaluronic acid (HA) by enzyme-linked immunosorbent assay, and detection of CK-20
      and hyaluronidase (HAase) by reverse transcription polymerase chain reaction (RT
      PCR) in urothelial cells from voided urine. RESULTS: HA mean rank was higher in
      benign and malignant groups than in the healthy group (P < 0.0001) and was
      significantly related to tumor grade (P = 0.021). HA best-cutoff, determined
      using receiver operating characteristic curve to discriminate between malignant
      and nonmalignant groups, was 58.5 units/mg protein at 85.8% sensitivity and 60.7%
      specificity. HAase RNA showed superior sensitivity (90.8%) over cytology (68.9%)
      and CK-20 (78.1%) with specificity of 93.4%, 98.1% and 80.2%, respectively. The
      sensitivity reached 94.7% at a specificity of 91.5% when combined with CK-20. All
      4 of the investigated markers were related to grade at P <0.05. Whereas only
      HAase and CK-20 were significantly related to stage (P < 0.05). As to
      schistosomiasis, only HAase RNA positivity was significantly associated (P =
      0.038). CONCLUSIONS: HAase RNA is a promising noninvasive test with high
      sensitivity and specificity in bladder carcinoma detection.

PMID- 15717322
TI  - The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in
      colorectal carcinoma.
AB  - BACKGROUND: Loss of the cell-cycle inhibitory protein p27Kip1 is associated with
      poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the
      result of increased proteasome-dependent degradation, mediated and rate-limited
      by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and
      cyclin-dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were
      found to be increased in some colorectal carcinomas, but their potential role as
      prognostic markers for survival is unknown. The present study was undertaken to
      assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma.
      MATERIALS AND METHODS: The expression of Skp2, Cks1, and p27Kip1 was examined by
      immunohistochemistry using highly specific antibodies on formalin-fixed, paraffin
      embedded tissue sections from 80 patients with colorectal carcinoma. RESULTS:
      Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss
      of tumor differentiation. A significant decrease in overall survival was observed
      in patients expressing high Skp2 or Cks1 levels, and in particular, patients with
      Stage II and III disease. Each protein provided significant additional prognostic
      information to that given by disease stage, tumor grade, or p27Kip1 expression.
      CONCLUSIONS: Results suggest that overexpression of Skp2 or Cks1 is strongly
      associated with poor prognosis and may thus be used as prognostic markers for
      overall survival in colorectal carcinoma.

PMID- 15717323
TI  - An overview of adverse events reported by participants in CDC's anthrax vaccine
      and antimicrobial availability program.
AB  - PURPOSE: The CDC's Anthrax Vaccine and Antibiotic Availability Program was
      implemented under an Investigational New Drug (IND) application to provide
      additional post-exposure prophylaxis for individuals potentially exposed to
      Bacillus anthracis in the fall of 2001. Participants were provided with two
      options: (1) 40 additional days of antimicrobial prophylaxis (i.e.,
      ciprofloxacin, doxycycline, or amoxicillin); or (2) 40 additional days of
      antimicrobial prophylaxis plus three doses of anthrax vaccine adsorbed (AVA).
      METHODS: Participants were monitored for adverse events (AEs). Participants were
      asked to complete 2-week AE diaries for 6 weeks post-enrollment, and
      approximately 2 months after enrollment, active surveillance was conducted
      through telephone interviews with 1113 (64%) participants. RESULTS: A total of
      1727 of approximately 10 000 previously prophylaxed persons enrolled to receive
      40 additional days of antibiotics. Of these, 199 opted at enrollment to receive
      three doses of AVA in addition to the additional 40 days of antibiotic. Overall,
      28% of participants reported at least one AE on their diaries. Results varied by
      surveillance mechanism, the diary data indicated differences in the proportion
      reporting AEs between participants receiving antibiotic only and participants
      receiving antibiotic and AVA. However, during the active 2-month telephone follow
      up, the rates of AEs reported for both the antibiotic only and antibiotic plus
      AVA treatment regimens were similar. Additionally, ciprofloxacin and doxycycline
      had similar AE profiles, with only rigors reported significantly more often among
      ciprofloxacin recipients. CONCLUSIONS: Overall, the rates of AEs experienced by
      all participants were acceptable given the seriousness of potential B. anthracis
      exposure.

PMID- 15717324
TI  - Role of interleukin-6 in cardiomyocyte/cardiac fibroblast interactions during
      myocyte hypertrophy and fibroblast proliferation.
AB  - The process of cardiac hypertrophy is considered to involve two components: that
      of cardiac myocyte (CM) enlargement and cardiac fibroblast (CF) proliferation.
      The interleukin-6 (IL-6) family cytokines have been implicated in a variety of
      cellular and molecular interactions between myocytes and non-myocytes (NCMs),
      which in turn have important roles in the development of cardiac hypertrophy. In
      the study of these interactions, we previously detected very high levels of IL-6
      in supernatants of a "dedifferentiated model" of adult ventricular CMs cultured
      with CFs. In the present study, we have used this in vitro coculture system to
      examine how IL-6 is involved in the interactions between CMs and CFs during CM
      hypertrophy and CF proliferation. IL-6 and its signal transducer, 130-kDa
      glycoprotein (gp130), were detected by immunostaining cultured CMs and CFs with
      anti-IL-6 or anti-gp130 antibodies. Addition of anti-IL-6 or anti-gp130
      antagonist antibodies into CM/CF cocultures induced a significant decrease in
      expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (beta
      MHC) in CMs. The presence of IL-6 antagonist also resulted in a decrease in the
      surface area of 12-day-old CMs cultured with CFs or in the presence of fibroblast
      conditioned medium (FCM), and decreased fibroblast proliferation in CM/CF
      cocultures, particularly in the presence of a gp130 antagonist. The results also
      show that angiotensin II (AngII) is mainly secreted by CFs and induces IL-6
      secretion in CMs cultured with CFs or with FCM. In addition, the effects of IL-6
      on cardiomyocyte hypertrophy and fibroblast proliferation were inhibited by
      addition of the AT-1 receptor antagonist, losartan. These results suggest that IL
      6 contributes significantly to CM hypertrophy by an autocrine pathway and to
      fibroblast proliferation by a paracrine pathway and that these effects could be
      mediated by AngII.

PMID- 15717325
TI  - Mapping the membrane proteome of Corynebacterium glutamicum.
AB  - In order to avoid the specific problems with intrinsic membrane proteins in
      proteome analysis, a new procedure was developed which is superior to the
      classical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) method in
      terms of intrinsic membrane proteins. For analysis of the membrane proteome from
      Corynebacterium glutamicum, we replaced the first separation dimension, i.e., the
      isoelectric focusing step, by anion-exchange chromatography, followed by sodium
      dodecyl sulfate (SDS)-PAGE in the second separation dimension. Enrichment of the
      membrane intrinsic subproteome was achieved by washing with 2.5 M NaBr which
      removed more than 35% of the membrane-associated soluble proteins. For the
      extraction and solubilization of membrane proteins, the detergent
      amidosulfobetaine 14 (ASB-14) was most efficient in a detailed screening
      procedure and proved also suitable for chromatography. 356 gel bands were
      spotted, and out of 170 different identified proteins, 50 were membrane-integral.
      Membrane proteins with one up to 13 transmembrane helices were found. Careful
      analysis revealed that this new procedure covers proteins from a wide pI range
      (3.7-10.6) and a wide mass range of 10-120 kDa. About 50% of the identified
      membrane proteins belong to various functional categories like energy metabolism,
      transport, signal transduction, protein translocation, and proteolysis while for
      the others a function is not yet known, indicating the potential of the developed
      method for elucidation of membrane proteomes in general.

PMID- 15717326
TI  - Proteomics analysis of growth hormone isoforms in the human pituitary.
AB  - In order to elucidate the roles of human growth hormone (hGH) in the normal
      (control) pituitary and in adenomas, the hGH isoforms in the human pituitary were
      analyzed with two-dimensional gel electrophoresis, immobilized metal affinity
      column (Ga(+3)) chromatography, mass spectrometry (MS), and bioinformatics.
      Twenty-four hGH-containing proteins, with significantly different expression
      proportions of their isoforms were found. The proportions of isoforms were as
      follows: isoform 1 (87.5%) > isoform 2 (8.1%) > isoform 3 (3.3%) > isoform 4
      (1.1%). Deamidation of asparagine to aspartate was identified with matrix
      assisted laser desorption/ionization-time of flight MS. Tandem mass spectrometry
      data demonstrated that hGH is a phosphoprotein (spot 6); phosphorylation was
      found at Ser-77 in the tryptic peptide (68)YSFLQNPQTSLCFSESIPTPSNR(90), at Ser
      176 in the tryptic peptide (172)FDTNSHNDDALLK(184), and at Ser-132 in the peptide
      (126)SLVYGASDSNVYDLLK(141). The phosphorylation sites at Ser-77 and Ser-176 were
      consistent with computer-program predictions (NetPhos). These results provide
      novel clues for further studies of the functions, and mechanisms of action, of
      hGH in the human pituitary and in growth hormone-related diseases.

PMID- 15717327
TI  - Effect of training datasets on support vector machine prediction of protein
      protein interactions.
AB  - Knowledge of protein-protein interaction is useful for elucidating protein
      function via the concept of 'guilt-by-association'. A statistical learning
      method, Support Vector Machine (SVM), has recently been explored for the
      prediction of protein-protein interactions using artificial shuffled sequences as
      hypothetical noninteracting proteins and it has shown promising results (Bock, J.
      R., Gough, D. A., Bioinformatics 2001, 17, 455-460). It remains unclear however,
      how the prediction accuracy is affected if real protein sequences are used to
      represent noninteracting proteins. In this work, this effect is assessed by
      comparison of the results derived from the use of real protein sequences with
      that derived from the use of shuffled sequences. The real protein sequences of
      hypothetical noninteracting proteins are generated from an exclusion analysis in
      combination with subcellular localization information of interacting proteins
      found in the Database of Interacting Proteins. Prediction accuracy using real
      protein sequences is 76.9% compared to 94.1% using artificial shuffled sequences.
      The discrepancy likely arises from the expected higher level of difficulty for
      separating two sets of real protein sequences than that for separating a set of
      real protein sequences from a set of artificial sequences. The use of real
      protein sequences for training a SVM classification system is expected to give
      better prediction results in practical cases. This is tested by using both SVM
      systems for predicting putative protein partners of a set of thioredoxin related
      proteins. The prediction results are consistent with observations, suggesting
      that real sequence is more practically useful in development of SVM
      classification system for facilitating protein-protein interaction prediction.

PMID- 15717329
TI  - Analysis of phosphatase and tensin homolog tumor suppressor interacting proteins
      by in vitro and in silico proteomics.
AB  - The phosphatase and tensin homolog (PTEN) tumor suppressor is a multifunctional
      protein deregulated in many types of cancer. To date, a comprehensive
      documentation of PTEN interacting proteins has not been performed. The goal of
      our study was to characterize the PTEN interactome using affinity pull-down and
      tandem mass spectrometry (MS/MS). Wild-type PTEN cDNA was inserted into pTRC-His2
      vector to create a 6-His tagged protein, which was expressed in Escherichia coli.
      Lysate from a human lymphoma cell line was used in pull-down assays, utilizing
      affinity for nickel-agarose beads. Bound proteins were eluted with imidazole,
      digested and analyzed on an LCQ DecaXP ion trap mass spectrometer. The nickel
      affinity pull-down efficiency was evaluated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blot analysis. Acquired data were
      searched against the NCBI nr.fasta nonredundant protein database using the
      SEQUEST algorithm and screened using INTERACT and ProteinProphet. All experiments
      were performed in duplicate with 6-His-lacZ serving as control. A total of 79
      proteins were identified in the wild-type 6-His-PTEN pull-down by MS/MS. We
      further validated a subset of the proteins present in the PTEN interactome by
      performing immunoprecipitation using an anti-PTEN antibody and establishing the
      presence of the proteins in the immunocomplex by Western blot analysis. A search
      of published PTEN interactions was also performed using Online Mendelian
      Inheritance in Man, Human Protein Reference Database, the IntAct Project
      database, and PubMed. This in silico analysis confirmed 42 out of 79 (53%) of the
      proteins identified by MS/MS. The remaining 37 proteins represent probable PTEN
      interactions not previously documented in public databases or reported in the
      literature. These results highlight the value of combining both in vitro
      biochemical approaches with in silico analyses for a comprehensive study of
      protein-protein interactions.

PMID- 15717328
TI  - A differential proteome in tumors suppressed by an adenovirus-based skin patch
      vaccine encoding human carcinoembryonic antigen.
AB  - We created an anti-tumor vaccine by using adenovirus as a vector which contains a
      cytomegalovirus early promoter-directed human carcinoembryonic antigen gene
      (AdCMV-hCEA). In an attempt to develop the skin patch vaccine, we epicutaneously
      vaccinated Balb/c mice with AdCMV-hCEA. After nine weeks post-immunization,
      vaccinated mice evoked a robust antibody titer to CEA and demonstrated the
      capability of suppressing in vivo growth of implanted murine mammay adenocarioma
      cell line (JC-hCEA) tumor cells derived from a female Balb/c mouse. Proteomic
      analysis of the tumor masses in the non-vaccinated naive and vaccinated mice
      reveal that six proteins change their abundance in the tumor mass. The levels of
      adenylate kinase 1, beta-enolase, creatine kinase M chain, hemoglobin beta chain
      and prohibitin were statistically increased whereas the level of a creatine
      kinase fragment, which is undocumented, was decreased in the tumor of vaccinated
      mice. These proteins may provide a vital link between early-stage tumor
      suppression and immune response of skin patch vaccination.

PMID- 15717330
TI  - Subproteomes of soluble and structure-bound Helicobacter pylori proteins analyzed
      by two-dimensional gel electrophoresis and mass spectrometry.
AB  - Helicobacter pylori is one of the most common bacterial pathogens and causes a
      variety of diseases, such as peptic ulcer or gastric cancer. Despite intensive
      study of this human pathogen in the last decades, knowledge about its membrane
      proteins and, in particular, those which are putative components of the type IV
      secretion system encoded by the cag pathogenicity island (PAI) remains limited.
      Our aim is to establish a dynamic two-dimensional electrophoresis-polyacrylamide
      gel electrophoresis (2-DE-PAGE) database with multiple subproteomes of H. pylori
      (http://www.mpiib-berlin.mpg.de/2D-PAGE) which facilitates identification of
      bacterial proteins important in pathogen-host interactions. Using a proteomic
      approach, we investigated the protein composition of two H. pylori fractions:
      soluble proteins and structure-bound proteins (including membrane proteins). Both
      fractions differed markedly in the overall protein composition as determined by 2
      DE. The 50 most abundant protein spots in each fraction were identified by
      peptide mass fingerprinting. We detected four cag PAI proteins, numerous outer
      membrane proteins (OMPs), the vacuolating cytotoxin VacA, other potential
      virulence factors, and few ribosomal proteins in the structure-bound fraction. In
      contrast, catalase (KatA), gamma-glutamyltranspeptidase (Ggt), and the neutrophil
      activating protein NapA were found almost exclusively in the soluble protein
      fraction. The results presented here are an important complement to genome
      sequence data, and the established 2-D PAGE maps provide a basis for comparative
      studies of the H. pylori proteome. Such subproteomes in the public domain will be
      effective instruments for identifying new virulence factors and antigens of
      potential diagnostic and/or curative value against infections with this important
      pathogen.

PMID- 15717331
TI  - C-terminal sequencing by mass spectrometry: application to gelatine-derived
      proline-rich peptides.
AB  - Protonated peptides derived from proline-rich proteins (PRP) are often difficult
      to sequence by standard collision-induced dissociation (CID) mass spectrometry
      (MS) due to preferential amide bond cleavage N-terminal to proline. In connection
      with bovine spongiform encephalopathy regulations, proteolytic products derived
      from the PRP collagen have been suggested as markers for contamination of animal
      feedstuffs with processed animal protein (Fernandez Ocana, M. et al., Analyst
      2004, 129, 111-115). Herein, we report the identification of these marker
      peptides using the strategy of C-terminal sequencing by CID MS from their sodium
      and lithium adducts. Upon fragmentation a new cationized peptide was produced
      that is one C-terminal amino acid shorter in length. This dissociation pathway
      allowed for the facile identification of the C-terminal residue by matrix
      assisted laser desorption/ionization tandem time-of-flight mass spectrometry.
      Each newly formed cationized peptide was further fragmented by up to seven stages
      of electrospray ionization ion trap MS. Proline-rich C-terminal sequence tags
      were established which permitted successful database identification of collagen
      alpha type I proteins.

PMID- 15717332
TI  - High-frequency health data and spline functions.
AB  - Seasonal variations are highly relevant for health service organization. In
      general, short run movements of medical magnitudes are important features for
      managers in this field to make adequate decisions. Thus, the analysis of the
      seasonal pattern in high-frequency health data is an appealing task. The aim of
      this paper is to propose procedures that allow the analysis of the seasonal
      component in this kind of data by means of spline functions embedded into a
      structural model. In the proposed method, useful adaptions of the traditional
      spline formulation are developed, and the resulting procedures are capable of
      capturing periodic variations, whether deterministic or stochastic, in a
      parsimonious way. Finally, these methodological tools are applied to a series of
      daily emergency service demand in order to capture simultaneous seasonal
      variations in which periods are different.

PMID- 15717333
TI  - The effects of intentional weight loss as a latent variable problem.
AB  - Although obesity is associated with increased mortality rate and short-term
      weight loss improves risk factors for mortality, it has not been convincingly
      shown that weight loss among obese people results in reduced mortality rate. When
      considering the human literature, it has been pointed out that weight loss is
      often a sign of illness and that investigators therefore need to separate
      intentional from unintentional weight loss. It has generally been assumed that
      among people who state that they do not intend to lose weight, weight change
      subsequently observed is unintentional. Among such people, weight loss has been
      consistently associated with increased mortality rate. Complementarily, it has
      generally been assumed that among people who state that they do intend to lose
      weight, weight change subsequently observed is intentional. In these people who
      are intending to lose weight, some studies show apparent benefits of weight loss,
      some are neutral, and some show deleterious effects. The overall conclusion that
      some reviewers have drawn from this literature is that intentional weight loss
      (IWL) is at best not beneficial and may even be harmful with respect to mortality
      rate. We believe that this conclusion is drawn by inappropriately conflating
      weight loss (or more generally weight change) among people intending to lose
      weight with IWL (or change). Herein, under certain assumptions, we: (1) show that
      the association between mortality rate and weight loss among people intending to
      lose weight and between mortality rate and IWL are two different things; (2) show
      that the association between IWL and mortality rate is an inherently unobservable
      entity; (3) derive a method for estimating the plausible range of true effect of
      IWL on mortality rate if one is willing to make a number of restrictive, but
      perhaps reasonable assumptions; and (4) illustrate the method by application to a
      data set involving middle-age onset calorie restriction in mice.

PMID- 15717334
TI  - Psychological wellbeing in later life: the longitudinal effects of marriage,
      widowhood and marital status change.
AB  - AIM: The study examined cross-sectionally and longitudinally psychological
      wellbeing in the context of marital status, gender, and age. METHOD: Measures
      were taken eight years apart for three groups: married at both interviews;
      widowed at both interviews; and married at first interview but widowed at third.
      Data were analysed using multiple regression models: dependent variables were
      morale and social engagement; independent variables were marital status, gender
      and age. RESULTS: Cross-sectionally significant differences were found for
      marital status and age for both morale and social engagement. Both widowed and
      newly widowed participants reported lower morale and social engagement than their
      married counterparts. In the longitudinal model, when prior levels of morale were
      taken into account, only age and being newly widowed contributed significantly to
      the variance (R2). The same pattern of results was found for social engagement.
      Gender was never significant. CONCLUSION: The results illustrate the value of
      modelling both cross-sectional and longitudinal data. The latter demonstrated
      that the size of the effect differed between those who had recently widowed and
      those who had been widowed for longer. The study shows that age needs to be taken
      into account when examining widowhood.

PMID- 15717335
TI  - Cognitive intervention for community-dwelling older persons with memory problems:
      telemedicine versus face-to-face treatment.
AB  - BACKGROUND: Memory complaints and decline in cognitive function are common in the
      elderly. Cognitive intervention has been shown to be beneficial in Alzheimer's
      disease (AD). However, few community-based cognitive intervention programs are
      available in Hong Kong. The aim of this project is to examine and compare the
      feasibility, acceptability, and clinical outcome of a cognitive intervention
      program for older patients with mild cognitive impairment and mild dementia using
      telemedicine versus a conventional face-to-face method. METHODS: Community
      dwelling older subjects with mild dementia or mild cognitive impairments were
      recruited from a community center. A total of 12 sessions of assessment and
      cognitive intervention were conducted via videoconferencing or by face-to-face
      method. Assessment included: Cantonese version of Mini Mental State Examination
      (C-MMSE), Cantonese version of Rivermead Behavioural Memory test (C-RBMT) and
      Hierarchic Dementia Scale (HDS). RESULTS: Twenty-two clients were recruited.
      There was significant and comparable cognitive improvement in clients in both
      treatment arms. The videoconference arm was highly accepted by the clients and
      the community center. Overall compliance rate of participants was above 95%.
      CONCLUSIONS: Telemedicine was a feasible, effective and acceptable means in
      providing cognitive assessment and intervention to older persons with mild
      cognitive deficits. Promoting such a program to other community settings would
      further enhance the accessibility of dementia service to the community.

PMID- 15717336
TI  - Beyond the global score of the Zarit Burden Interview: useful dimensions for
      clinicians.
AB  - OBJECTIVES: The purpose of this study was to explore the structure of the Zarit
      Burden Interview (ZBI) for informal caregivers of patients suffering from AD or
      related disorders, and to examine the relations of the dimensions found with
      functional disabilities and other patient health indicators. DESIGN: 152 dyads of
      community-dwelling older adults with dementia and their primary caregivers were
      analysed. METHODS: Caregiver burden was measured by the 22-item ZBI. Caregivers'
      and care recipients' characteristics were collected with the MDS (Minimum Data
      Set) of the RAI (Resident Assessment Instrument) Home Care instrument. Data on
      dementia (diagnosis, severity, MMSE) were also obtained. Burden data were
      analysed by principal component analysis (PCA) with varimax rotation.
      Relationships between scores on PCA factors and care recipients' health
      indicators were studied with inferential statistical tests. RESULTS: Three
      dimensions of burden were found: effect on the social and personal life of
      caregivers, psychological burden and feelings of guilt. Some health variables
      were linked to these dimensions. Spouses and children perceived burden
      differently. Spouse caregivers emphasized the deterioration of their personal and
      social life. Children, less involved in daily care, were more prone to feel guilt
      that they were not doing enough for their parent.

PMID- 15717337
TI  - Seasonal mood variation in the elderly: the Leiden 85-plus study.
AB  - BACKGROUND: The influence of seasonal changes on mood and behaviour is called
      seasonality. The prevalence of seasonality in elderly subjects is unknown. AIM:
      To investigate the seasonality pattern in mood and behaviour at old age. METHODS:
      All subjects from the Leiden 85-plus Study with an MMSE score of 19 or more were
      assessed for depressive feelings at age 85 and yearly thereafter. The influence
      of time of the year, duration of sunlight, daylight, and rain on the prevalence
      of depressive symptoms was assessed using linear mixed models for repeated
      measurements. RESULTS: There was no significant seasonal pattern in the data
      (p=0.44). Within each of the four years of observation (85, 86, 87 and 88 years)
      and all years combined, there was also no significant association between the one
      month cumulation of duration of sunlight, daylight, or rain and the score on the
      GDS (all p-values >0.05). The results of either the one week or three-month
      accumulation of sunlight, daylight, or rain were comparable to the one-month
      results. CONCLUSIONS: Estimates of prevalence of seasonality reported in the
      literature might be overestimated or a remarkable difference between young and
      old subjects exists.

PMID- 15717338
TI  - Clinical trials of potential antidepressants: to what extent are the elderly
      represented: a review.
AB  - BACKGROUND: There is widespread use of antidepressants in the elderly population.
      The principle of treatment of depression, however, is derived mostly from studies
      employing young adults and healthy elderly. This article reviews the literature
      on the extent to which the elderly are represented in clinical trials of
      potential antidepressants. METHOD: Medline search of relevant articles of
      clinical trials of potential antidepressants. RESULTS: The maximum age of
      inclusion for most clinical trials was 65 years. The highest age reported for
      depressed subjects was 90 years. There was no clear consensus on who were
      considered to be elderly; clinical trials conducted on the elderly included
      subjects who were 50, 55, or 60 years and over. Pharmacological studies on
      healthy subjects were most often done on young adults, age range 18 to 65 years.
      The period of study was relatively shorter for clinical trials done on elderly
      subjects. There was however, no difference in the exclusion or inclusion criteria
      between studies done in young and elderly subjects. CONCLUSIONS: Elderly subjects
      aged 75 years and over were clearly underrepresented in the clinical trials of
      potential antidepressants. For drugs that are used by the elderly, in its pivotal
      studies for registration, the inclusion of at least 25% of subjects aged 75 years
      and over is recommended.

PMID- 15717339
TI  - Quality of life in dementia--a one-year follow-up study.
AB  - BACKGROUND: Quality of life (QoL) is becoming an increasingly used outcome
      measure in both clinical practice and research but little is known about QoL in
      dementia and how it may change over time. OBJECTIVE: To study longitudinal change
      in quality of life over a period of one year in 60 people with dementia aged 65
      years or over. METHODS: The original sample was selected from inpatient, day
      hospital, nursing home and residential home settings within a London Mental
      Health Trust. The QoL-AD, DQoL and EQ-5D were assessed at baseline and repeated
      one-year later. At follow-up the CSDD, MMSE and RAID were also completed.
      RESULTS: Fifty-eight people were traced and of these 40 (69%) were alive at
      follow up. There was no mean change in quality of life over the one-year period,
      however around half of the people had increases or decreases in their quality of
      life. The only significant predictor of quality of life at follow-up was initial
      quality of life (p < 0.0005). Quality of life at follow-up correlated
      significantly with depression (p < 0.0005) and anxiety (p <0.01) but not with
      cognition. CONCLUSION: The main finding of this study is that people with
      dementia do not perceive that their quality of life declined over a period of one
      year. More people were able to complete the QoL-AD than the DQoL or EQ-5D at
      follow-up and it seemed easier to use for people with severe dementia. Future
      research should investigate how quality of life changes over longer time periods
      with larger samples and in relation to specific interventions.

PMID- 15717340
TI  - Relationship of exercise and other risk factors to depression of Alzheimer's
      disease: the LASER-AD study.
AB  - BACKGROUND: Depression is common in Alzheimer's disease (AD; 5-35%). It is
      associated with increased disability, cost of care and carer burden. Exercise is
      known to be associated with a lower prevalence of depression across the age range
      but little is known about its relationship to depression in AD. AIMS: To
      investigate exercise and putative risk factors for depression in a community
      based sample of people with AD representative of the range of cognitive
      impairment found in the population with dementia. METHODS: Information was
      collected from 224 people with AD and their caregiver using standardised
      cognitive, psychological and behavioural instruments. Exercise levels were
      classified into three categories: absent, moderate, and vigorous, using the
      previous two weeks exercise levels to confirm regularity and recency. RESULTS:
      9/51 (17.6%) depressed participants took exercise compared with 76/173 (43.9%)
      non-depressed [odds ratio (OR)=2.9, confidence interval (CI)=1.5-5.6, p=0.001].
      Not taking part in other activities (hobbies and interests) was associated with
      depression but less so than lack of exercise. Independent predictors of
      depression were: lack of exercise (p <0.001, OR=3.4, CI = 1.7-7.2), taking
      cholinesterase inhibitors (p <0.05, OR=2.4, CI = 1.2-4.9) and having less
      involvement in hobbies or interests (p <0.05, OR = 1.2, CI = 1.0-1.5).
      CONCLUSION: None of the traditional risk factors for depression in older people
      were associated with depression in AD. Taking regular exercise may protect
      against depression in AD.

PMID- 15717341
TI  - White matter lesions on magnetic resonance imaging and their relationship with
      vascular risk factors in memory clinic attenders.
AB  - BACKGROUND: The association between white matter lesions on magnetic resonance
      imaging (MRI) and the presence of vascular risk factors has been investigated in
      different populations, and results have varied widely. However, this relationship
      has not been adequately addressed in memory clinic attenders who have relatively
      early cognitive impairment. OBJECTIVES: This study was undertaken to determine
      the relationship between the severity of white matter lesions and vascular risk
      factors in elderly subjects referred to a Memory Clinic, irrespective of their
      diagnoses. Patients attending the Memory Clinic had relatively early, mild
      cognitive impairment and differed, in this respect, from typical unselected
      community-based samples and from patients with established dementia. The study
      also investigated whether periventricular and deep white matter lesions differed
      in their relationship with vascular risk factors. METHODS: All patients assessed
      in the Memory Clinic at Leicester General Hospital between April 1998 and October
      2000 who had undergone an MRI scan were included in the study. They received a
      comprehensive clinical and cognitive assessment, a standard dementia laboratory
      screen and evaluation of vascular risk factors. MRI scans were reviewed by two
      independent raters and semi-quantitative ratings of the severity of white matter
      lesions were made using standardised protocols. The relationship between cerebral
      white matter lesions and vascular risk factor variables was examined by multiple
      linear regression. RESULTS: One hundred and seventy-seven subjects were included
      in the study. The mean age was 69.8 and the mean MMSE score was 23.2. Of the risk
      factors investigated, only age and prior cerebrovascular disease were
      significantly associated with severe periventricular white matter lesions; age,
      hypertension and diabetes were significantly associated with severe deep white
      matter lesions. CONCLUSIONS: Periventricular and deep white matter lesions are
      differentially influenced by vascular risk factors.

PMID- 15717342
TI  - Cognitive and functional neuroimaging correlate for anosognosia in mild cognitive
      impairment and Alzheimer's disease.
AB  - OBJECTIVES: To investigate the correlation between anosognosia and behavioural
      symptoms, performance on executive tests, and frontal cortex regional cerebral
      blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and
      mild Alzheimer's disease (AD). METHODS: From a prospective Memory Clinic cohort
      including consecutively referred patients, age 60 years or above, and with MMSE
      score 20 or above, 36 patients with AD and 30 with MCI were included in this
      study. Anosognosia was assessed using a categorical scale and discrepancy scores
      between patients' and relatives' reports on a 20-item Memory Questionnaire (MQ).
      Behavioural symptoms were assessed with Frontal Behavioural Inventory (FBI).
      Executive functions were examined with a range of neuropsychological tests. Tc99m
      HMPAO SPECT was obtained in an unselected sample of 55 of the 66 patients, and
      rCBF was analysed in six cortical frontal regions. RESULTS: Insight was equally
      impaired in the two patient groups. A significant correlation was found between
      impaired awareness and dementia severity (MMSE). Discrepancy-scores on the MQ
      were significantly correlated to scores on FBI and to rCBF in the right inferior
      frontal gyrus, but not to executive tests. The groups classified by the
      categorical ratings 'full', 'shallow' and 'no' awareness were not characterized
      by differences in behavioural symptoms, executive performance or frontal rCBF.
      CONCLUSIONS: Impaired awareness is associated with behavioural symptoms and may
      reflect functional impairment in the right inferior frontal cortex.

PMID- 15717343
TI  - Mortality from dementia in a community-dwelling Brazilian population.
AB  - BACKGROUND: The influence of dementia on mortality has not yet been reported for
      a Latin American country. OBJECTIVES: To evaluate the influence of dementia on
      mortality of a community-dwelling elderly population in Brazil, and to verify the
      extent to which the diagnosis of dementia is reported on death certificates.
      METHODS: A cohort of 1,656 individuals, aged 65 and over, was screened for
      dementia at their domiciles, in 1997. The same population was re-evaluated in
      2000, and information on deaths was obtained from relatives and from the
      municipal obituary service. Kaplan-Meier curves were used for the survival
      analysis, and the mortality risk ratio (MMR) was calculated using Cox
      proportional hazards models. RESULTS: We obtained data from 1,393 subjects,
      corresponding to 84.1% of the target population. The number of deaths was 58
      (51.3%) among the patients with dementia and 163 (12.7%) among those without
      dementia in 1997 (p <0.0001). Dementia and Alzheimer's disease (AD) decreased
      survival, with hazards ratios of 5.16 [95% Confidence Interval (CI): 3.74-7.12]
      for dementia and 4.76 (95% CI: 3.16-7.18) for AD. The Cox proportional hazards
      model identified dementia (MMR=3.92, 95% CI: 2.80-5.48) as the most significant
      predictor of death, followed by age, history of stroke, complaints of visual
      impairment and heart failure and by severe arterial hypertension in the baseline
      evaluation. Dementia and/or AD were mentioned in only 12.5% of the death
      certificates of individuals with dementia. CONCLUSIONS: Dementia causes a
      significant decrease in survival, and the diagnosis of dementia is rarely
      reported on death certificates in Brazil.

PMID- 15717344
TI  - Comorbidity of depression and anxiety in nursing home patients.
AB  - OBJECTIVES: To assess the occurrence and risk indicators of depression, anxiety,
      and comorbid anxiety and depression among nursing home patients and to determine
      whether depression and anxiety are best described in a dimensional or in a
      categorical classification system. METHODS: DSM and subthreshold anxiety
      disorders, anxiety symptoms, major and minor depression and depressive symptoms
      were assessed in 333 nursing home patients of somatic wards of 14 nursing homes
      in the north west of the Netherlands with the Schedules for Clinical Assessment
      in Neuropsychiatry (SCAN) and the Geriatric Depression Scale (GDS). Comorbidity
      was studied along a severity gradient. Logistic regression analyses were carried
      out to identify demographic, health-related, psychosocial and care-related
      correlates of anxiety and depression. RESULTS: The prevalence of pure depression
      (PD) was 17.1%, of pure anxiety (PA) 4.8%, and of comorbid anxiety and depression
      (CAD) 5.1%. Comorbidity increased dependent on severity of both anxiety and
      depression. Different patterns of risk indicators were demonstrated for PA, PD
      and CAD for the investigated baseline characteristics. CONCLUSIONS: Comorbidity
      of anxiety and depression is most prevalent in the more severe depressive and
      anxious nursing home patients. The gradual increase of comorbidity of anxiety and
      depression dependent on the levels of severity of depression and anxiety suggests
      that for nursing home patients a dimensional classification of depression and
      anxiety is more appropriate than a categorical one. The observed differences in
      patterns of risk indicators for PA, PD and CAD support a distinguishing of
      anxiety and depression. Future studies are needed to assess the effect of
      treatment of PA, PD and CAD in nursing home patients.

PMID- 15717345
TI  - The brief Kingston Standardized Cognitive Assessment--revised.
AB  - OBJECTIVES: The Kingston Standardized Cognitive Assessment-Revised (KSCA-R) was
      designed to be a cognitive screening tool available to health professionals who
      were not trained in specialized cognitive assessment techniques. It was
      introduced to bridge the gap between brief, narrowly focused rating scales, and
      intensive, expensive, full neuropsychological assessments. We now present the
      Brief Kingston Standardized Cognitive Assessment-Revised (BriefKSCA-R). METHODS:
      Groups of Alzheimer's disease patients, patients suffering from other dementias,
      and a group of normal community dwelling elderly were assessed using the
      BriefKSCA-R. RESULTS: This shortened version of the full Kingston Standardized
      Cognitive Assessment-Revised can be given in half the time while retaining most
      of the full KSCA-R's effectiveness. CONCLUSIONS: Suitable for a quick screening,
      or follow-up of patients already more fully assessed.

PMID- 15717346
TI  - Children's fears and anxieties.

PMID- 15717347
TI  - Treating opiate addiction, Part I. Detoxification and maintenance.

PMID- 15717348
TI  - Moods and markets.

PMID- 15717349
TI  - Children of schizophrenic mothers: tracking their early lives.

PMID- 15717350
TI  - Questions & answers. My elderly friend has a serious clutter problem. She can't
      throw things away or organize them, and her apartment is so stuffed that it is
      hard to get around. She has tried herbs, hypnosis, and sessions with so-called
      experts, but nothing works. Could you explain this problem and describe how she
      can be helped?

PMID- 15717351
TI  - New research data show more drug resistance but also more care options. While
      better treatments are available, more can be done.
AB  - While clinicians and researchers are seeing increasing numbers of HIV patients
      with multidrug-resistant virus, there are indications that some existing drug
      combinations continue to be potent against resistant virus.

PMID- 15717352
TI  - HIV-resistance evolution requires new strategies. Mutation risk higher if HIV RNA
      increases.
AB  - A new study finds that 60% of HIV patients on stable therapy with detectable
      viral replication have a rate of new HIV mutations of about 1.5 mutations per
      year.

PMID- 15717353
TI  - New studies highlight HIV-resistance trends. NNRTIs show upward trend.
AB  - Two separate studies have found that some types of HIV drug resistance have
      declined or leveled off at the same time others have increased.

PMID- 15717354
TI  - New class of inhibitor may attack resistance. Potential drug could be cost
      efficient.
AB  - There is new hope for a cost-efficient treatment for HIV-1 infected patients who
      no longer respond to protease inhibitor (PI) treatment due to multidrug
      resistance.

PMID- 15717355
TI  - Drug-resistance patterns in women discovered. Resistance testing necessary,
      expert says.
AB  - If HIV-1 drug resistance is found in a woman's plasma, it's likely the same
      resistance is present in her genital tract, suggesting that drug resistance among
      pregnant, HIV-infected women, requires further investigation, a new study shows.

PMID- 15717356
TI  - New Congress poses challenges for advocates. Key changes in Congress could have
      impact.
AB  - No one is worried that a financially strapped federal government might kill Ryan
      White Care Act funding, but AIDS advocates say they are concerned about what will
      happen with the bill in a slightly different political environment this year.

PMID- 15717357
TI  - New microbicides enter trials in United States.
AB  - Two potential candidates in the microbicide research pipeline are set to be
      examined in clinical trials, with research to focus on the safety and
      acceptability in healthy women and women infected with HIV.

PMID- 15717358
TI  - FDA notifications. New antiretroviral guidelines issued.

PMID- 15717359
TI  - Top stories of 2004. Bad nukes comes in threes.

PMID- 15717361
TI  - Top stories of 2004. HAART and the heart.

PMID- 15717360
TI  - Top stories of 2004. Perinatal transmission interventions: the benefits come with
      resistance.

PMID- 15717362
TI  - Top stories of 2004. When to start: guidelines and intuition.

PMID- 15717363
TI  - Top stories of 2004. Resistance rates: high in new infections, higher in treated
      ones.

PMID- 15717364
TI  - Top stories of 2004. Uncertainty about treatment of acute HIV infection.

PMID- 15717365
TI  - Top stories of 2004. STIs in chronic infection: the jury is still out.

PMID- 15717366
TI  - Top stories of 2004. Back to the future: lopinavir/ritonavir as "monotherapy".

PMID- 15717367
TI  - Top stories of 2004. ACTG 5095: efavirenz beats AZT + 3TC + abacavir.

PMID- 15717368
TI  - Top stories of 2004. To 3TC or not to 3TC?

PMID- 15717369
TI  - Top stories of 2004. Nevirapine and efavirenz: similar efficacy, different
      toxicities, and better separately than combined.

PMID- 15717370
TI  - Top stories of 2004. DNA-MVA prime boost: another vaccine candidate bites the
      dust.

PMID- 15717371
TI  - Meeting notes from ICAAC. Ritonavir-boosted tipranavir proves beneficial in
      treatment-experienced patients.

PMID- 15717372
TI  - Meeting notes from ICAAC. Tenofovir + ddI: a combination to avoid.

PMID- 15717373
TI  - Meeting notes from ICAAC. Tenofovir + emtricitabine vs. AZT + 3TC.

PMID- 15717374
TI  - Meeting notes from ICAAC. Prevalence and predictors of R5 and X4 tropism.

PMID- 15717375
TI  - Meeting notes from ICAAC. Choosing the right HCV-coinfected patients to treat.

PMID- 15717376
TI  - Meeting notes from ICAAC. Promising early results for a novel CCR5 antagonist.

PMID- 15717377
TI  - Meeting notes from ICAAC. D-D4FC (Reverset): further data on treatment
      experienced patients.

PMID- 15717378
TI  - Meeting notes from ICAAC. NRTI-only regimens: making a comeback?

PMID- 15717379
TI  - Weekend treatment interruptions for certain well-controlled patients: interview
      with Cal Cohen, M.D. Interview by John S. James.
AB  - Dr. Cohen and others at the Community Research Initiative are studying a schedule
      of five days on certain antiretroviral regimens and two days off, for certain
      patients whose virus is well suppressed. The goal is to reduce side effects and
      cost, and to make the regimens easier to take. We asked about the results so far.

PMID- 15717380
TI  - Behind "AIDS breakthrough" headlines, December 2004: important research, not so
      new.
AB  - The mid-December press reports about an AIDS drug breakthrough were exaggerated,
      but the research described is important. It concerns the development of a class
      of related experimental drugs that work like efavirenz or nevirapine, but appear
      to be more powerful and much less subject to resistance.

PMID- 15717381
TI  - Sculptra (formerly New Fill) for facial wasting--where to find information on the
      patient-assistance program.
AB  - Dermik Laboratories has started a patient-assistance program that provides free
      or low-cost drug to patients who meet certain income and other eligibility
      requirements. Information is changing rapidly, so we provide Web, email, and
      telephone sources to check.

PMID- 15717382
TI  - Warning: do not combine Reyataz and Prilosec.
AB  - The combination has been found to reduce blood levels of the antiretroviral to
      about a quarter of what they should be.

PMID- 15717383
TI  - Treatment interruption: most patients could not maintain immune control.
AB  - Some patients treated very early with an experimental protocol (that stopped and
      restarted antiretroviral treatment when certain conditions were met) were able to
      stop antiretrovirals entirely and control their viral load without the drugs for
      at least 90 days. But after two years, only three of fourteen were still able to
      control the virus without treatment.

PMID- 15717384
TI  - India changes patent law to meet WTO treaty, making new medicines less available
      to most citizens, other countries.
AB  - India changed its pharmaceutical patent law to conform to the U.S.-European
      system, just ahead of a Jan. 1 World Trade Organization deadline--meaning that
      most new medicines (patentable in 1995 or later) will be priced out of reach of
      the great majority of people in India--and in Africa and other poor regions as
      well. "The real issue for the multinational corporations is not the poor-country
      markets, which are financially small and unattractive, but the poor-country
      examples. How would thousands of people in rich countries, especially the U.S.,
      be persuaded to accept death from cancer and other diseases because they cannot
      pay tens of thousands of dollars a year for a new generation of treatments that
      could save their lives--if companies in India could manufacture and sell the same
      treatments for a small fraction of the price?"

PMID- 15717385
TI  - Africa: children's access to prophylaxis may improve after medical study, new WHO
      recommendations.
AB  - On November 22, 2004, days after The Lancet reported that the cheap antibiotic co
      trimoxazole (Septra, Bactrim, and other brand names) had dramatically reduced
      death in a group of Zambian children with HIV, the World Health Organization
      (WHO), UNAIDS and UNICEF released a statement recommending the drug for all
      children with HIV symptoms in poor countries. But activists say the global health
      authorities' seemingly quick action came years--even decades--late, and it will
      take a lot more work to actually deliver the drug's lifesaving promise.

PMID- 15717386
TI  - Nevirapine misinformation: will it kill?
AB  - In mid December 2004 three Associated Press stories created widespread doubts
      about nevirapine, a well-known, critically important drug that can prevent HIV in
      many of the 1,800 babies now infected every day by their mothers in childbirth.
      The media allegations that went around the world grew out of a bitter personal
      and personnel dispute between two employees at the U.S. National Institutes of
      Health. No new information about nevirapine was released; doctors know that it
      still has the same risks and benefits after the newspaper stories as before. But
      many experts fear that the emotions released by the worldwide misinformation will
      result in many HIV-positive mothers getting no treatment and unnecessarily
      infecting their children with HIV. Here is background that has been missing in
      many of the news reports.

PMID- 15717387
TI  - Missing conferences followup: four meetings' history found.
AB  - The abstracts of four major AIDS conferences that were unavailable online or in
      libraries around the world have now been found after AIDS Treatment News asked
      people to look for copies. Please check old files, boxes, bookshelves, and other
      archives for other missing conferences listed here.

PMID- 15717388
TI  - Buyers' club list, December 2004.
AB  - Our annual list of AIDS buyers' clubs and related resources.

PMID- 15717389
TI  - National symptom surveillance using calls to a telephone health advice service-
      United Kingdom, December 2001-February 2003.
AB  - INTRODUCTION: Recent terrorist activity has highlighted the need to improve
      surveillance systems for the early detection of chemical or biologic attacks. A
      new national surveillance system in the United Kingdom (UK) examines symptoms
      reported to NHS Direct, a telephone health advice service. OBJECTIVES: The aim of
      the surveillance system is to identify an increase in symptoms indicative of
      early stages of illness caused either by a deliberate release of a biologic or
      chemical agent or by common infections. METHODS: Data relating to 10 key
      syndromes (primarily respiratory and gastrointestinal) are received
      electronically from 23 call centers covering England and Wales. Data are analyzed
      daily and statistically significant excesses, termed exceedances, in calls are
      automatically highlighted and assessed by a multidisciplinary team. RESULTS:
      During December 2001-February 2003, a total of 1,811 exceedances occurred, of
      which 126 required further investigation and 16 resulted in alerts to local or
      national health-protection teams. Examples of these investigations are described.
      CONCLUSION: Surveillance of call-center data has detected substantial levels of
      specific syndromes at both national and regional levels. Although no deliberate
      release of a biologic or chemical agent has been detected thus far by this or any
      other surveillance system in the UK, the NHS Direct surveillance system continues
      to be refined.

PMID- 15717390
TI  - Field investigations of emergency department syndromic surveillance signals--New
      York City.
AB  - INTRODUCTION: The New York City (NYC) Department of Health and Mental Hygiene
      (DOHMH) has operated a syndromic surveillance system based on emergency
      department (ED) chief-complaint data since November 2001. This system was created
      for early detection of infectious-disease outbreaks, either natural or
      intentional. However, limited documentation exists regarding epidemiologic field
      investigations conducted in response to syndromic surveillance signals.
      OBJECTIVE: DOHMH conducted field investigations to characterize syndromic
      surveillance signals by person, place, and time and to determine whether signals
      represented true infectious-disease outbreaks. METHODS: A DOHMH physician reviews
      ED-based syndromic surveillance results daily to look for signals. When
      necessary, field investigations are conducted and consist of a review of the
      patient line list, telephone interviews with hospital staff, chart reviews,
      interviews with patients, and collection and testing of specimens. RESULTS: In
      November 2002, a series of citywide signals for diarrhea and vomiting syndromes,
      which coincided with institutional outbreaks consistent with viral
      gastroenteritis, prompted DOHMH to send mass e-mail notification to NYC ED
      directors and institute collection of stool specimens. Three of four specimens
      collected were positive for norovirus. In December 2002, DOHMH investigated why
      an ED syndromic signal was not generated after 15 ill patients were transferred
      to a participating ED during a gastrointestinal outbreak at a nursing home. Field
      investigation revealed varying chief complaints, multiple dates of ED visits, and
      a coding error in a complementary DOHMH syndromic system, and confirmed a
      seasonal norovirus outbreak. During March 2003, the system generated a 4-day
      citywide respiratory signal and a simultaneous 1-day hospital-level fever signal
      in a predominantly Asian community. In those instances, epidemiologic
      investigation provided reassurance that severe acute respiratory syndrome was not
      present. CONCLUSION: Detailed field investigations of syndromic signals can
      identify the etiology of signals and determine why a given syndromic surveillance
      system failed to detect an outbreak captured through traditional surveillance.
      Validation of the utility of syndromic surveillance to detect infectious-disease
      outbreaks is necessary to justify allocating resources for this new public health
      tool.

PMID- 15717391
TI  - Should we be worried? Investigation of signals generated by an electronic
      syndromic surveillance system--Westchester County, New York.
AB  - INTRODUCTION: In January 2003, the Westchester County Department of Health (WCDH)
      began conducting electronic syndromic surveillance of hospital emergency
      department (ED) chief complaints. Although methods for data collection and
      analysis used in syndromic surveillance have been described previously, minimal
      information exists regarding the responses to and investigations of signals
      detected by such systems. This paper describes WCDH's experience in responding to
      syndromic surveillance signals during the first 9 months after the system was
      implemented. OBJECTIVES: The objectives of this analysis were to examine WCDH's
      responses to signals detected by the county's syndromic surveillance system.
      Specific goals were to 1) review the actual complaints reported by hospital EDs
      to determine whether complaint data were accurately identified and classified
      into syndrome categories, and provide feedback from this review to data
      collection and analysis staff to refine text terms or filters used to identify
      and classify chief complaints; 2) develop procedures and response algorithms for
      investigating signals; 3) determine whether signals correlated with reportable
      communicable diseases or other incidents of public health significance requiring
      investigation and intervention; and 4) quantify the staffing resources and time
      required to investigate signals. METHODS: During January 27-October 31, 2003,
      electronic files containing chief-complaint data from seven of the county's 13
      EDs were collected daily. Complaints were classified into syndrome categories and
      analyzed for statistically significant increases. A line listing of each
      complaint comprising each signal detected was reviewed for exact complaint,
      number, location, patient demographics, and requirement for hospital admission.
      RESULTS: A total of 59 signals were detected in eight syndrome categories:
      fever/influenza (11), respiratory (6), vomiting (11), gastrointestinal
      illness/diarrhea (8), sepsis (7), rash (7), hemorrhagic events (3), and
      neurologic (6). Line-listing review indicated that complaints routinely were
      incorrectly identified and included in syndrome categories and that as few as
      three complaints could produce a signal. On the basis of hospital, geographic,
      age, or sex clustering of complaints, whether the complaint indicated a
      reportable condition (e.g., meningitis) or potentially represented an unusual
      medical event, and whether rates of hospital admission were consistent with
      medical conditions, 34 of 59 signals were determined to require further
      investigation (i.e., obtaining additional information from ED staff or medical
      providers). Investigation did not identify any reportable communicable disease or
      other incidents of public health significance that would have been missed by
      existing traditional surveillance systems. Nine staff members spent 3 hours/week
      collectively investigating signals detected by syndromic surveillance.
      CONCLUSIONS: Standardized sets of text terms used to identify and classify
      hospital ED chief complaints into syndrome categories might require modification
      on the basis of hospital idiosyncrasies in recording chief complaints. Signal
      investigations could be reasonably conducted by using local health department
      resources. Although no communicable disease events were identified, the system
      provided baseline and timely objective data for hospital visits and improved
      communication among county health department and hospital ED staff.

PMID- 15717392
TI  - Public Health Information Network--improving early detection by using a standards
      based approach to connecting public health and clinical medicine.
AB  - Public health departments and their clinical partners are moving ahead rapidly to
      implement systems for early detection of disease outbreaks. In the urgency to
      develop useful early detection systems, information systems must adhere to
      certain standards to facilitate sustainable, real-time delivery of important data
      and to make data available to the public health partners who verify, investigate,
      and respond to outbreaks. To ensure this crucial interoperability, all
      information systems supported by federal funding for state and local preparedness
      capacity are required to adhere to the Public Health Information Network
      standards.

PMID- 15717393
TI  - Information system architectures for syndromic surveillance.
AB  - INTRODUCTION: Public health agencies are developing the capacity to automatically
      acquire, integrate, and analyze clinical information for disease surveillance.
      The design of such surveillance systems might benefit from the incorporation of
      advanced architectures developed for biomedical data integration. Data
      integration is not unique to public health, and both information technology and
      academic research should influence development of these systems. OBJECTIVES: The
      goal of this paper is to describe the essential architectural components of a
      syndromic surveillance information system and discuss existing and potential
      architectural approaches to data integration. METHODS: This paper examines the
      role of data elements, vocabulary standards, data extraction, transport and
      security, transformation and normalization, and analysis data sets in developing
      disease-surveillance systems. It then discusses automated surveillance systems in
      the context of biomedical and computer science research in data integration, both
      to characterize existing systems and to indicate potential avenues of
      investigation to build systems that support public health practice. RESULTS: The
      Public Health Information Network (PHIN) identifies best practices for essential
      architectural components of a syndromic surveillance system. A schema for
      classifying biomedical data-integration software is useful for classifying
      present approaches to syndromic surveillance and for describing architectural
      variation. CONCLUSIONS: Public health informatics and computer science research
      in data-integration systems can supplement approaches recommended by PHIN and
      provide information for future public health surveillance systems.

PMID- 15717394
TI  - Perspective of an emergency physician group as a data provider for syndromic
      surveillance.
AB  - The need for enhanced biologic surveillance has led to the search for new sources
      of data. Beginning in September 2001, Emergency Medical Associates (EMA) of New
      Jersey, an emergency physician group practice, undertook a series of surveillance
      projects in collaboration with state and federal agencies. This paper examines
      EMA's motivations and concerns and discusses the collaborative opportunities
      available to data suppliers for syndromic surveillance. Motivations for supplying
      data included altruism and public service, previous involvement in terrorism and
      disaster preparedness, academic research interests, and the opportunity to find
      added value in the group's existing information systems. Concerns and barriers
      included cost, maintaining patient confidentiality, and challenges in interacting
      with the public health community. The extensive and carefully maintained
      electronic medical record enabled EMA to conduct multiple studies in
      collaboration with state and federal agencies. The electronic medical record
      provides useful data that might be more sensitive and specific in detecting
      outbreaks than the patient-chief-complaint data more commonly used for
      surveillance. EMA's experience also indicates that opportunities exist for the
      public health community to work with emergency physicians and emergency physician
      groups as suppliers of data. Such collaborations not only are useful for
      syndromic surveillance systems but also can help build relations that might
      facilitate a response to an actual biologic attack.

PMID- 15717395
TI  - SARS Surveillance Project--Internet-enabled multiregion surveillance for rapidly
      emerging disease.
AB  - INTRODUCTION: On March 15, 2003, CDC requested health-care and public health
      agencies to conduct surveillance for severe acute respiratory syndrome (SARS).
      The SARS Surveillance Project (SARS-SP) was established to rapidly implement
      multiregional SARS surveillance in emergency departments (EDs) by using existing
      Internet-based tools. OBJECTIVES: The objectives of SARS-SP were to 1)
      disseminate and update SARS screening forms for ED triage, 2) establish
      surveillance for SARS syndrome elements by using Regional Emergency Medicine
      Internet (REMI), 3) expand surveillance to multiple regions, and 4) evaluate the
      usefulness of Internet tools for agile surveillance during a rapidly emerging
      global epidemic. METHODS: SARS-SP developed, distributed, and updated an Internet
      based triage form to identify patients for infection control and public health
      reporting. EDs then were invited to report visit frequencies with various SARS
      syndrome elements to local public health authorities by using the REMI Internet
      application (first in one metropolitan area, and later in four). After pilot
      testing in one metropolitan area, the surveillance system was implemented in
      three others. RESULTS: Active syndromic surveillance was established by health
      departments in Milwaukee, Wisconsin; Denver, Colorado; Akron, Ohio; and Fort
      Worth, Texas. A total of 27 EDs reported syndrome frequencies from >146,000
      patient encounters. CONCLUSIONS: ED and public health partners reported being
      satisfied with the system, confirming the usefulness of Internet tools in the
      rapid establishment of multiregion syndromic surveillance during an emerging
      global epidemic.

PMID- 15717396
TI  - Health information privacy and syndromic surveillance systems.
AB  - The development of syndromic surveillance systems to detect potential terrorist
      related outbreaks has the potential to be a useful public health surveillance
      activity. However, the perception of how the Health Insurance Portability and
      Accountability Act of 1996 (HIPAA) Privacy Rule applies to the disclosure of
      certain public health information might affect the ability of state and local
      health departments to implement syndromic surveillance systems within their
      jurisdictions. To assess this effect, a multiple-question survey asked
      respondents to share their experiences regarding patient confidentiality and
      HIPAA Privacy Rule requirements when implementing syndromic surveillance systems.
      This assessment summarizes the results of a national survey of state terrorism
      preparedness coordinators and state epidemiologists and reflects the authors' and
      others' experiences with implementation.

PMID- 15717397
TI  - Consequences of the withdrawal of dimetridazole on intestinal parasitism in
      ducks.

PMID- 15717398
TI  - Pertussis vaccines--WHO position paper.

PMID- 15717399
TI  - Patient safety culture and leadership in Canada's academic health sciences
      centres.

PMID- 15717400
TI  - Provider-based professional clinical and financial implementation services 2004.

PMID- 15717402
TI  - New stem cell center at Cornell.

PMID- 15717401
TI  - [Ambulatory vascular surgery].

PMID- 15717403
TI  - Less invasive surgery for colon cancer.

PMID- 15717404
TI  - Tumor size versus biology in screen lung cancer with CT.

PMID- 15717405
TI  - Herceptin and chemotherapy combination active in advanced breast cancer.

PMID- 15717406
TI  - Linking better surveillance to better outcomes.

PMID- 15717408
TI  - Targeting angigenesis in colorectal cancer.

PMID- 15717407
TI  - Early success of combined EGFR and Her2 receptor blockade as a clinical strategy
      in breast cancer.

PMID- 15717409
TI  - MSH6 mutations and risk of uterine cancer.

PMID- 15717410
TI  - Spiers Memorial Lecture. Recent experimental advances in studies of liquid/liquid
      interfaces. Concluding remarks.

PMID- 15717411
TI  - Who highlights health in the 2015 development blueprint.

PMID- 15717412
TI  - 700,000 people living with AIDS in developing countries now receiving treatment.

PMID- 15717413
TI  - Monovalent oral polio vaccine: Gates Foundation funds new polio vaccine to
      accelerate eradication efforts.

PMID- 15717414
TI  - CDC issues updated guidelines on use of antiretroviral drugs to prevent HIV
      infection after sexual, drug use, and accidental exposure.

PMID- 15717415
TI  - [Screening of the colorectal cancer].

PMID- 15717416
TI  - The twelfth annual meeting of the European Society of Gene Therapy.

PMID- 15717417
TI  - A historical review of artificial cornea research in Japan.
AB  - Little is known or understood about the history of artificial cornea
      (keratoprosthesis) in Japan, mainly because of the unavailability and linguistic
      inaccessibility of the relevant publications. Rather strangely also, the Japanese
      scholars themselves have manifested only slight interest in reviewing the topic,
      even in their own language. As a result, the research on artificial cornea in
      Japan showed in fact the same pattern of historical development as that seen in
      the Western world. After audacious beginnings in the 19th century, an interlude
      of about half a century followed, when the interest of ophthalmologists was
      deflected to penetrating keratoplasty as a means to fight corneal blindness. The
      introduction in medical use of man-made polymeric materials in the 1950s
      triggered a revival of research on artificial cornea in Japan, and the next two
      decades were rich in ideas, achievements, and a plethora of reports, all
      published in Japanese. In the 1980s, the developmental work on keratoprosthesis
      became incorporated into the field of biomaterials, and the creation of materials
      able to mimic the corneal tissue was established as a leading concept, resulting
      in original designs with some sophistication. At the same time. the English
      language started to be used extensively for dissemination of results. These
      trends have continued to date. Based on rigorous documentation, we traced the
      history of research on artificial cornea in Japan from its origin to our time.

PMID- 15717418
TI  - Synthesis and biological evaluation of gramicidin S dimers.
AB  - The design and synthesis of analogues of the cyclic beta-sheet gramicidin S (GS),
      having additional functionalities in their turn regions, is reported. The
      monomeric GS analogues were transformed into dimers and their activities towards
      biological membranes, through antimicriobial and hemolytic assays, were
      evaluated. Finally, conductivity measurements have been performed to elucidate
      ion channel forming properties.

PMID- 15717419
TI  - Pro/con clinical debate: It is acceptable to stop large multicentre randomized
      controlled trials at interim analysis for futility. Con: the hazards of stopping
      for futility.

PMID- 15717420
TI  - Historical, new, and reemerging links between human and animal health.

PMID- 15717421
TI  - Images in Mississippi medicine. Coney Hospital, 1861-65.

PMID- 15717423
TI  - Proceedings of the 21st Workshop of the Scandinavian Society for Cell Toxicology.
      19-21 September 2003, Tampere, Finland.

PMID- 15717422
TI  - Current Status of Dependence/Abuse Studies: Cellular and Molecular Mechanisms of
      Drugs of Abuse and Neurotoxicity. July 30-August 1, 2003, Kyoto, Japan.
      Conference proceedings.

PMID- 15717424
TI  - Proceedings of the 1st International Conference on Polyphenols and Health. Vichy,
      France, November 18-21, 2004.

PMID- 15717425
TI  - Congenital, reactive, and neoplastic disorders in pediatric hematopathology:
      impact of flow cytometric and molecular methodologies on diagnosis and treatment.
      Proceedings of the 2003 Society for Hematopathology/European Association for
      Haematopathology Workshop.

PMID- 15717426
TI  - Patient and Family Fact Sheet. Tourette syndrome.

PMID- 15717427
TI  - Vibration and components of bone strength.

PMID- 15717429
TI  - [Proceedings of the 127th Internal Medicine Seminar and 20th Vanysek Seminar held
      March 19 2004 in Brno].

PMID- 15717428
TI  - [Comment on article: Pancreatic fistulas after distal resection].

PMID- 15717431
TI  - The premie-neuro: a clinical neurologic examination of premature infants.
AB  - PURPOSE: To develop a neurologic assessment tool, the Premie-Neuro, for very low
      birth weight (VLBW) infants. INSTRUMENT DEVELOPMENT: Neurologic data were
      collected during the coursc of the NICU stay. Factor analysis was utilized to
      determine the strength of relationships between items and to reduce the initial
      number of test items. SAMPLE: An NICU cohort of 86 preterm infants was enrolled.
      Mean birth weight was 1165.8 +/- 446.7 grams, and mean gestational age at birth
      was 28.8 +/- 3.2 weeks. METHOD: Seventy-five neurologic and behavioral
      characteristics were assessed in week 1 of life and every 2 weeks thereafter
      until 38 weeks posreonceprional age. MAIN OUTCOME VARIABLE: Three factors, the
      Neurologic Scale, the Movement Scale, and the Responsiveness Scale, described the
      neurologic examination. RESULTS: Factor reliability was calculated for internal
      consistency (Cronbach alpha coefficient) and ranged from .73 to .82. The Premie
      Neuro can be utilized with VLBW infants to monitor neurologic development during
      NICU care.

PMID- 15717430
TI  - Holding the very low birth weight infant: skin-to-skin techniques.
AB  - Skin-to-skin holding has been reported as a valuable intervention for preterm
      infants for over a decade. However, many neonatal intensive care units are not
      practicing this therapy and cite lack of protocols and techniques as a barrier.
      This article describes in detail the nursing considerations and techniques
      involved to successfully implement skin-to-skin holding for very low birth
      weight, technology-dependent infants. NICU protocols can be derived from this
      article.

PMID- 15717432
TI  - Use of sleep studies in the neonatal intensive care unit.
AB  - Although early hospital discharge of infants can be both cost-effective and
      better for developmental care and parent-infant bonding, neonatal caregivers need
      to ensure infant safety. One of the concerns of early discharge is the risk that
      premature babies may continue to have apnea, bradycardia, and oxygen desaturation
      after discharge and that these events can be serious enough to increase morbidity
      and mortality. The discharging provider bears the responsibility of assessing
      each infant's risk for persistent apnea and providing the care and monitoring
      appropriate for his presumed risk level. Presently there is no universally
      accepted testing method that can accurately predict which infants will experience
      significant apnea. Neonatal sleep studies are one of the objective methods being
      evaluated to identify infants at risk for persistent apnea. This article
      addresses arguments for and against the use of sleep studies to determine the
      risk of apnea in neonates about to be discharged, types of sleep studies and what
      they test, and how sleep studies can be useful in determining infant care.

PMID- 15717433
TI  - Mongolian spots in the newborn: do they mean anything?
AB  - Mongolian spots are the most frequently seen birthmarks in infants. They have
      almost universally been regarded as benign cutaneous manifestations that have no
      clinical significance. Recently, however, there have been studies suggesting that
      Mongolian spots manifest more often in children with certain inborn errors of
      metabolism, including mucopolysaccharidosis and GM1 gangliosidosis.

PMID- 15717435
TI  - Data collection and study implementation.
AB  - Every step of the research process involves decisions that must be made. In
      almost all cases, there are many possible choices, and none of them is wrong.
      However, it is up to the researcher to consider all of the options and
      systematically eliminate possibilities based on a theoretical framework, previous
      findings and methods described in the literature, or circumstances specific to
      each research question. When the methods used are less than ideal for some
      reason, the researcher should identify the problems as limitations to the study.
      Sometimes the limitations restrict the population to which the data can be
      generalized. In other instances, the limitations identify new areas of study that
      the current investigation did not address, but for which the current data provide
      support.

PMID- 15717434
TI  - Pathophysiology and current management of necrotizing enterocolitis.
AB  - Necrotizing enterocolitis continues to be a common and life-threatening
      gastrointestinal emergency in the low birth weight infant. Prematurity, ischemia,
      enteral feeding, and infectious disease have been identified as common risk
      factors, however the exact cause of NEC other than prematurity is yet to be
      identified. Good assessment skills by the nurse are imperative, because clinical
      signs of NEC can be both subtle and catastrophic. Frequent radiographs are
      essential for the diagnosis of NEC and ongoing assessment of neonates diagnosed
      with NEC. Radiographs including an abdominal flat plate examination and a left
      lateral decubitus film to evaluate for free air should be obtained every 6-8
      hours in the neonates with Stages II and III NEC.

PMID- 15717436
TI  - Point-of-care testing: all good?

PMID- 15717437
TI  - Immunological aspects of endometriosis.
AB  - The immune system probably plays a role in the onset and development of
      endometriosis. A general picture can be proposed. In some women refluxing
      endometrial cells are not destroyed, either because the patient is genetically
      programmed not to respond to endometrial antigens, or because the reflux is so
      abundant that the scavenging capacity of the peritoneal immune cells is
      overloaded. Refluxing cells could be protected due to an abnormal adherence to
      the mesothelium which exceptionally expresses certain adhesive molecules.
      Undestroyed, these endometrial cells would cause an inflammation with activation
      of macrophages. Not only does the peritoneum protect these endometrial cells, but
      it also produces abnormal quantities of chemotactic and angiogenic cytokines
      (interleukin-8). Macrophages facilitate development via growth factors such as
      transforming growth factor P. Immunosuppressive factors block the cytotoxic
      activity of natural killer (NK) cells. Activated macrophages present antigens of
      endometrial cells to T cells which will co-operate with B cells to synthesize
      autoantibodies. Synthesized antibodies protect the ectopic endometrium and could
      worsen the dysfunction of local NK cells. A vicious circle is set up involving
      all the partners of the immune system. It is as yet impossible to pinpoint the
      triggering mechanism. The primary defect could be localized on the endometrium,
      macrophages already activated by an extrinsic factor (infection, spermatozoa,
      chemical substances), the uterus or the tubo-uterine junction. The two
      pathophysiological theories put forward to explain endometriosis are linked by a
      defective immune system. Indeed, once the vicious circle is set up, growth and
      angiogenic factors could induce metaplasia of the already irritated mesothelium.

PMID- 15717438
TI  - The peritoneal environment in endometriosis.
AB  - The local environment of peritoneal fluid (PF) surrounding the endometriotic
      implant is immunologically dynamic and links the reproductive and immune systems.
      Peritoneal fluid contains a variety of free floating cells, including
      macrophages, mesothelial cells, lymphocytes, eosinophils and mast cells.
      Macrophages are attracted to the peritoneal environment more abundantly than any
      other cell type. These scavengers promote cellular growth and viability through
      secretion of growth factors and cytokines. It is now becoming evident that
      cytokines play an important role in reproduction at various levels, including
      gamete function, fertilization and embryo development, implantation and
      postimplantation survival of the conceptus. Peritoneal fluid has been shown to
      affect negatively ovum capture by the fimbria, sperm survival, spermatozoon
      oocyte interaction and embryonic development. We have recently identified the
      presence of two pro-inflammatory chemoattractant cytokines for
      monocyte/macrophages (MCP-1) and for granulocytes (interleukin-8, IL-8) in the
      PF. Concentrations of both IL-8 and MCP-1 are not only elevated in PF of women
      with endometriosis compared to those without endometriosis, but they are related
      to the severity of the disease. Over the past 70 years, at least a dozen theories
      have been proposed to explain the histogenesis and aetiology of endometriosis. It
      appears that the aetiology is multifactorial, and today a composite theory of
      retrograde menstruation with implantation of endometrial fragments in conjunction
      with peritoneal factors to stimulate cell growth is the most widely accepted
      explanation for peritoneal endometriosis.

PMID- 15717439
TI  - Development, structure and function of the cranial suspensory ligaments of the
      mammalian gonads in a cross-species perspective; their possible role in effecting
      disturbed testicular descent.
AB  - The present review aims to present a perspectiveon a relatively unknown part of
      the mammalian internal genitalia: their cranial suspensory apparatus. This
      apparatus shows wide divergence of development when examined during the fetal
      period or during adulthood, in males or females, or in individuals across a
      variety of species. In rats and other mamalian species the apparatus undergoes a
      distinct patern of sexually dimorphic development and fetal testicular androgens
      are proposed to play a key role in this process. Extensive development of this
      suspensory apparatus in females is argued to be a part of the anatomical
      adaptations of the genital apparatus to support the internal genitalia throughout
      pregnancy, including the relatively enormous growth towards the time of
      parturition. Minor development of this apparatus in males is judged to be a part
      of the anatomical requirements allowing developing testes to become displaced
      from the dorsal abdominal wall during the first stage of testicular descent.
      Extensive development of this suspensory apparatus in males generally seems to
      hinder testicular descent. Accordingly, the apparatus is well developed in so
      called testicond species which do not show testis descent as a part of their
      normal male genital development. Furthermore, arguments are adduced that
      inappropriate and extensive development in species with testis descent may be a
      key aetiological factor in the disturbance of this process. Diagnosis and
      treatment of human cryptorchidism might profit from including an analysis of the
      development and function of (remnants of) the cranial testicular and epididymal
      suspensory apparatus.

PMID- 15717440
TI  - Modern surgical approaches to female reproductive tract.
AB  - Laparoscopic and hysteroscopic surgery have changed the management of many
      gynaecological disorders. Procedures that previously required a long duration of
      hospitalization can now be done on an outpatient basis or with a short hospital
      stay. Surgical treatment remains the definitive and universal treatment of
      ectopic pregnancy and it can be safely done by laparoscopy. Most reproductive
      operations are done by laparoscopy and the results appear to be similar to those
      obtained with laparotomy. Those needing a laparotomy will be better treated by in
      vitro fertilization. Laparoscopic ovarian drilling is a viable alternative for
      infertile women with polycystic ovarian syndrome. Most ovarian cysts and
      endometriosis should be treated by laparoscopy. Although uterine myomas can be
      removed by laparoscopy, the uterine integrity after the procedure is
      questionable. Surgery should be reserved for women who have completed their
      family or those with pedunculated or shallow intramural myomas. Alternatively, a
      laparoscopically assisted myomectomy can be done. For laparoscopic hysterectomies
      for benign lesions, supracervical hysterectomy appears to be a good option.
      Hysteroscopy has changed our management, particularly for abnormal uterine
      bleeding. A submucous myoma and polyp can be removed by hysteroscopy and, as an
      alternative to hysterectomy, endometrial ablation can be done. In the future,
      most procedures will be done by endoscopy and laparotomy will be reserved only
      for selected cases.

PMID- 15717441
TI  - The assessment of tubal functional status by tubal perfusion pressure
      measurements.
AB  - The measurement of tubal perfusion pressures (TPP) is a recent advance in the
      field of gynaecoradiology. Measurement of TPP involves a standardized technique
      using transcervically placed tubal catheters which is reviewed in detail. TPP
      assesses the functional status of the Fallopian tubes, i.e. their ability to
      permit pregnancy. Infertile patients with normal TPP demonstrated a higher
      pregnancy rate (10 out of 23) than patients with elevated TPP (four out of 24, P
      < 0.05). Analysis of patients who had undergone a laparoscopy as well as
      measurement of TPP suggest that elevated TPP are highly indicative of tubal
      endometriosis. Tubal catheterization with wireguides was successful in reducing
      mildly elevated TPP. The impact of this procedure on pregnancy rates is not
      known. The use of the gynaecoradiological techniques discussed in this paper has
      reduced the need for diagnostic laparoscopy at our centre by >60%. This was
      achieved without compromise in pregnancy rates and has resulted in a considerable
      reduction in cost.

PMID- 15717442
TI  - Diagnosis and management of organic ovarian cysts: indications and procedures for
      laparoscopy.
AB  - In the field of gynaecological surgery, the past few years have been significant
      due to the development of operative laparoscopy. Originally recommended for the
      diagnosis of female infertility, over the past 15 years laparoscopy has acquired
      the standing of a surgical discipline in its own right. Laparoscopic surgical
      treatment of ovarian cysts, whether conservative or radical, has now been
      completely standardized. The aim of this work is to specify the indications,
      procedures and risks involved with this surgery as applied to organic ovarian
      cysts. Only benign ovarian cysts are suitable for treatment by laparoscopic
      surgery; ovarian cancer must always be handled by classic surgery using a mid
      line laparotomy. Given that clinical and other pre-operative investigations can
      give only an indication, ovarian lesions require surgical investigation to
      diagnose the histological type. Laparoscopy appears to be as reliable as
      laparotomy when assessing whether an ovarian tumour is malignant. The risk of
      parietal contamination and peritoneal dissemination if a malignancy is not
      recognized means that, if there are no signs of extra-ovarian extension,
      adnexectomy is mandatory whenever there is the slightest doubt. This adnexectomy
      must obey two important rules: it must be accomplished without rupturing the
      cyst, and the cyst must be placed, intact, inside an endoscopic bag before being
      extracted. Provided that all stages of the procedure, from pre-operative work-up
      to the initial diagnostic phase of the laparoscopy, are carried out meticulously,
      laparoscopic surgery is reliable for both the diagnosis and the management of
      benign organic-ovarian cysts.

PMID- 15717443
TI  - Ethics and reproductive medicine.
AB  - This article surveys relevant moral and ethical implications of reproductive
      medicine, excluding any aspects of contraception. To maintain the methodological
      priority of a moral perspective, it focuses on moral theory and ethics in general
      before looking at the impact of ethics on the different techniques applied in
      reproductive medicine. We suggest that discourse ethics should be centre-stage
      among the moral perspectives, since it has a unique capacity to synthesize, gauge
      and emulate other moral perspectives without necessarily replacing them.
      Questions of spousal fidelity, parental identity, sexual relations, reshaping of
      family ties, preimplantation diagnosis, discarding of human life, up to the
      question of what kind of life is generally acknowledged as worth living, and
      which is not, all these are morally significant topics. As well as providing a
      description of the techniques used in reproductive medicine, our article presents
      a rationale for charting potentials for moral problems. This renders it possible
      to elucidate the moral costs of each of the options offered by reproductive
      medicine in the light of whatever moral view one identifies with.

PMID- 15717444
TI  - Preventive vaccination of lactating and pregnant heifers against lungworm: safety
      and protection in three dairy herds.
AB  - A study of the safety of a vaccine against lungworm was carried out with pregnant
      and lactating heifers from three dairy herds with a previous history of lungworm
      outbreaks in adult cows. Half of the heifers were vaccinated while the other half
      were not. A slight temporary cough following the vaccination was only observed in
      one herd. No adverse effects on pregnancy or milk production were seen. All
      heifers were serologically and coprologically examined before the first, before
      and after the second immunization, 3 months after introduction to pasture and at
      the end of the grazing season. Serological and faecal examination of the dairy
      cows before introduction into pasture confirmed the presence of at least one
      Dictyocaulus viviparus carrier in each herd. Lungworm infection occurred in all
      herds during the grazing season, most prominently in the herd with the highest
      number of heifers. In this herd, mild coughing associated with the lungworm
      infection was noticed, especially in the non vaccinated heifers. No other signs
      or symptoms were observed. It is concluded that a vaccine against D. viviparus
      can be used safely in heifers, before they are introduced into the adult herd,
      and that this vaccine can be used as a preventive measure against lungworm
      outbreaks in adult cattle.

PMID- 15717445
TI  - [Suffering of life?].

PMID- 15717446
TI  - [Predecessors: veterinarians from earlier times (57). Karl Johann Christian
      Dammann (1839-1914)].

PMID- 15717447
TI  - [The mental health status of local veterinarians, 2 years after the foot and
      mouth disease crisis in their practice].

PMID- 15717448
TI  - [Headlines in the experience of the foot and mouth disease crisis: interviews
      with involved local veterinarians and advice for the future].

PMID- 15717449
TI  - [Headquarters of the Large Animal Health Services. Who are they and what do they
      do? An interview with Prof. Dr. Arjan Stegeman by M.M. Sloet van Oldruitenborgh
      Oosterbaan].

PMID- 15717450
TI  - ["The group Veterinarians in Professional Life (DIB) sees them flying!" Group DIB
      visiting KLM cargo animal hotel].

PMID- 15717452
TI  - [How is the education to become a para-veterinarian assistant organized?].

PMID- 15717451
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Coins made to commemorate the establishment of
      the Veterinary University in Utrecht, the Netherlands].

PMID- 15717453
TI  - [Goodwill: the salary in relation to the work week, the organization of the
      practice and the gross turnover and the net gain].

PMID- 15717454
TI  - Morphological aspect of the thyroid ima artery in human fetuses.
AB  - Some morphological characteristics of the variable thyroid ima artery were
      investigated on the injected fetal arteries and explained on their 106 static
      images. Thyroid ima artery of different origin was proven in 18 (16.9%) cases.
      With respect to the vascular sources of the investigated artery, the branching of
      the brachiocephalic trunk and right common carotid artery was found in 72.1% of
      the cases. At the same time, the thyroid ima and superior or inferior thyroid
      arteries were obvious in all cases, as well as the presence of single or multiple
      variations and abnormalities of neighbouring arteries in 38.8% of the cases. No
      major anatomical difference was noted between the fetal form of the variable
      thyroid artery reported in this paper and the postnatal form reviewed from the
      literature. Thyroid ima artery probably represents an example of the arterial
      self-differentiation and induced differentiation of the unilateral vascular
      trunk.

PMID- 15717455
TI  - Influence of nerve growth factor upon the injured peripheral nerve in the absence
      of its distal part.
AB  - Transected peripheral nerve can be protected with different supplementations. One
      of them is implantation of dead-ended connective tissue chambers filled with
      fibrin and growth-promoting substances. The aim of this study was to find whether
      nerve growth factor (NGF) applied by means of such method exerts neuroprotective
      effect upon transected sciatic nerves. Study was performed on the adult male
      Wistar C rats. Connective tissue chambers grew around the silicone tubes
      implanted under their skin. Chambers were then filled with fibrin (control group)
      or fibrin with NGF solution (NGF group). Right sciatic nerve was cut, its distal
      stump was removed and its proximal stump was introduced into the chamber.
      Following 4 weeks DiI was applied to the free end of implant. The labeled
      motoneurons in the slices obtained from L3-L4 spinal cord segments and the number
      of myelinated nerve fibers present in the middle part of the chambers were
      counted. Acetylcholinesterase-positive fiber endings inside the chambers were
      also visualized. Our data showed that the number of motor neurons and their
      diameters as well as the number of myelinated fibers were higher in the NGF group
      when compared to the control group, but these differences were not significant.
      In both groups parallelly arranged acetylcholinesterase-positive nerve fibers
      were present. The obtained results show that NGF has no influence on regeneration
      of the motor component of the rat sciatic nerves in adult animals.

PMID- 15717456
TI  - Approach to the study of human anatomy.
AB  - The first thing to do to describe the human body is to define the anatomical
      position and the bilateral symmetry which characterise every Metazoi (man
      included) and permit us to study the body in its two symmetric halves; the left
      and right sides are the result of a virtual cut on a vertical and median plan.
      This is followed by a resume of the general structures and the vocabulary of the
      outer shapes of the human body; its direction (it will be helpful to use the
      virtual geometric parallelepiped made by three couples of planes one orthogonal
      to the other); levels of structural organization (chemical, cellular, tissue,
      organ and the system level; the highest is the organism level). After that, rules
      and principles are enunciated in the four fundamental laws of anatomy regarding
      the organ structures and their systems studied by the surface, gross
      (macroscopic), systemic, regional and constitutional type anatomy. There is also
      some information concerning education and research, the competence of the Human
      Anatomy as recommended by art. 1 of D.M. 23. XI. 1999 of the Italian law. Later
      what Richard Snell written in the preface to "Clinical Anatomy for Medical
      Students" about the importance of the knowledge of human anatomy for medical and
      surgical applications will be reported.

PMID- 15717457
TI  - Activated hepatic stellate cells in liver cirrhosis. A morphologic and
      morphometrical study.
AB  - Hepatic stellate cells have been considered the most important cell-type involved
      in hepatic fibrogenesis. Proliferation and differentiation of hepatic stellate
      cells into myofibroblast-like cells has been related to the development of liver
      fibrosis. The alpha-actin expressed by hepatic stellate cells was considered a
      marker of their activation to myofibroblast-like cell. The aim of this study is
      to evaluate the changes in morphology, distribution, percentage and alpha-smooth
      muscle actin expression of hepatic stellate cells in normal and cirrhotic livers,
      and to correlate activated hepatic stellate cells with the progression of
      fibrosis. Human liver biopsies (n=121) were divided in five groups: 1) normal
      livers (controls); 2) cirrhosis post-HCV hepatitis; 3) cirrhosis post-HBV
      hepatitis; 4) non viral related cirrhosis; 5) recurrent HCV hepatitis after
      orthotopic liver transplantation. Samples immunostained with anti alpha-smooth
      muscle actin antibody by immunoperoxidase method were semi-quantitatively
      evaluated. Liver fibrosis was quantified by computer image analysis on specimens
      stained with Masson's trichrome. In normal adult livers stellate cells were very
      rarely stained for alpha-smooth muscle actin. In cirrhotic livers, a strongly
      enhanced percentage of stellate cells expressing alpha-smooth muscle actin was
      detected in cirrhotic fragments with respect to the control group, with a
      significant correlation between alpha-smooth muscle actin positive stellate cells
      and the volume fraction of fibrosis. Moreover, liver biopsies of recurrent
      hepatitis revealed an increased number of activated stellate cells compared to
      normal livers, and intermediate volume fraction of fibrosis. These results
      confirmed that a direct correlation existed between activated stellate cells and
      the progression of fibrosis. Alpha-smooth muscle actin confirmed to be a reliable
      marker of hepatic stellate cells activation also in precocious stages of the
      disease.

PMID- 15717458
TI  - The sensitive innervation of the ostrich nasal mucosa.
AB  - The sensitive innervation of the ostrich's nasal mucosa, through impregnative
      gold chloride methods, was investigated. The autonomy innervation, constituted by
      ganglion cells placed along the course of nerve trunks was particularly
      represented in the respiratory tract of the nasal cavity. The somatic nerve
      component, composed by free and capsulated endings, was especially distributed in
      the vestibular district. The nerve corpuscles were morphologically classified as
      Pacini, Pacini-like, Golgi-Mazzoni and Herbst. Further investigations must be
      expected to attribute an effective functional role particularly to this last
      nerve component.

PMID- 15717459
TI  - [Effectiveness of ropivacaine and fentanyl for postoperative epidural analgesia
      following thoracic surgery].
AB  - BACKGROUND: Epidural ropivacaine is now a common drug used for postoperative
      analgesia. However, little information is available concerning regression of
      sensory blockade and analgesia following prolonged epidural infusion of
      ropivacaine. We investigated the efficacy of ropivacaine and fentanyl for
      postoperative analgesia after thoracic surgery. METHODS: Thirty patients
      undergoing thoracic surgery were enrolled. After surgery with general and
      thoracic epidural anesthesia, continuous epidural infusion of 0.2%
      ropivacaine+fentanyl (1.67 microg x ml(-1)) was started at a rate of 6 ml x h(-1)
      for patients whose height was more than 155 cm and 4 ml x h(-1) for those below
      155 cm with possibility of an additional bolus injection of 3 ml at least every
      60 min. RESULTS: An additional epidural injection of 3 ml produced a decrease in
      VAS without significant changes of vital signs. The greatest VAS was 10+/-25 mm
      in the incision site and 36+/-38 mm in the ipsilateral shoulder. Sensory blockade
      was sustained until the morning after the day of surgery. Also blood pressure and
      heart rate were stable throughout the observation period. There were no adverse
      effects except for slight nausea in three patients. CONCLUSIONS: A bolus of 3 ml
      with continuous 4-6 ml x h(-1) epidural injection of ropivacaine plus a small
      dose of fentanyl would decrease postoperative pain with stable vital signs in
      patients after thoracic surgery.

PMID- 15717461
TI  - [Gastric fluid volume and pH in scheduled surgical patients following
      unrestricted oral fluid intake until two hours before surgery].
AB  - BACKGROUND: In scheduled surgery, drinking is generally restricted for 6-8 hours
      before operation to avoid aspiration pneumonia induced by aspiration of residual
      gastric contents. However, the restriction is hard for patients and also there is
      no evidence of reduction of such a risk. We examined the correlation between
      water intake and residual gastric content. METHODS: We studied 60 patients
      scheduled for gynecological operations (ASA 1 or 2). They were allowed to drink
      clear water freely until two hours before operation, and timing and volume of
      their drinking were recorded. In addition, volume and pH of the residual gastric
      content were measured at induction of anesthesia. RESULTS: The mean volumes of
      fluids they had are 157 ml (range 0-750 ml) in the morning, and 486 ml (range 80
      1300 ml) in the afternoon. The patients took more water as the scheduled time of
      operation became nearer. There was no correlation between the volume of
      preoperative drinking with the volume and pH of gastric content. CONCLUSIONS:
      Intake of clear water until two hours before surgery has been shown to be safe
      and contribute to patients' satisfaction.

PMID- 15717460
TI  - [Advantage of ropivacaine for postoperative epidural analgesia following leg
      orthopedic surgery].
AB  - BACKGROUND: Epidural administration of local anesthetics may lead to effective
      pain relief. However, tachyphylaxis or other problems following prolonged
      epidural anesthesia may develop and in many cases difficulties exist in the
      maintenance of the similar degree of sensory blockade. The present study was
      therefore performed to investigate the analgesic effect of continuous
      postoperative epidural infusion of ropivacaine with fentanyl in comparison with
      that of bupivacaine or ropivacaine alone. METHODS: After leg orthopedic surgery
      with lumbar combined spinal-epidural anesthesia, thirty-six patients were
      randomized to one of the three postoperative epidural infusion groups:
      bupivacaine 0.125%, ropivacaine 0.2%, or ropivacaine 0.2% with 2.2 microg x ml(
      1) (400 microg x 180 ml(-1)) of fentanyl. Continuous epidural infusion was
      started at a rate of 6 ml x h(-1) with possibility of an additional bolus
      injection of 3 ml at least every 60 min. Pain was assessed using a 10-cm visual
      analog scale (VAS) just before and 15 min after epidural bolus injections, and 15
      20 h after the start of continuous epidural infusion as the severe at pain
      through the observation. The spread of analgesia (loss of sharpness in pinprick
      perception) and motor block (Bromage scale) were evaluated bilaterally. Systolic
      and diastolic blood pressure and heart rate were also measured. RESULTS: The
      epidural bolus infusion was associated with a significant decrease of VAS (P <
      0.001) and stable blood pressure and heart rate in all groups. The maximal VAS in
      patients receiving 0.2% ropivacaine+fentanyl was significantly less compared to
      that in the other two groups. The regression of sensory blockade was
      significantly prolonged in patients treated with ropivacaine+fentanyl. There was
      no significant difference in the spread of sensory analgesia between 20 min and
      15-20 h after the continuous epidural anesthesia in this group. None of the
      patients developed adverse effects such as respiratory depression, nausea, and
      pruritus. CONCLUSIONS: Epidural injection of ropivacaine with fentanyl decreased
      postoperative pain with stable vital signs in patients undergoing leg orthopedic
      surgery, as compared to bupivacaine or ropivacaine alone, possibly because of the
      maintenance of sensory blockade by ropivacaine and enhancement of this sensory
      blockade by fentanyl.

PMID- 15717462
TI  - [Intra-operative ketamine administration reduced the level of post-thoracotomy
      pain].
AB  - BACKGROUND: Two different types of post-operative pain (such as acute pain and
      chronic pain) occur in patients undergoing thoracotomy. It has been suggested
      that the acute post-thoracotomy pain consists of inflammatory pain and chronic
      post-thoracotomy pain caused by intercostal neuralgia. In the present study, we
      examined the effect of intra-operative administration of ketamine, an NMDA
      receptor antagonist, on the acute and chronic post-thoracotomy pain. METHODS:
      Sixteen patients were assigned to one of two groups (ketamine or control). The
      ketamine group received a ketamine bolus (1 mg x kg(-1)) just before the skin
      incision, followed by continuous infusion of ketamine (1 mg x kg(-1) x hr(-1))
      during surgery. RESULTS: Verbal rating scores (VRSs) at rest and on cough were
      significantly lower in the ketamine group on day 1 and VRS of chronic pain was
      also significantly lower in the ketamine group 4 weeks after the surgery.
      CONCLUSIONS: These data suggest that post-thoracotomy pain might be mediated by
      NMDA receptor dependent central sensitization and that the intra-operative
      administration of ketamine might block the development of the NMDA receptor
      dependent central sensitization.

PMID- 15717463
TI  - [Detection of deep vein thrombosis in preoperative patients using venous
      ultrasonography].
AB  - BACKGROUND: Using Doppler ultrasonography (US), deep vein thrombosis (DVT) has
      been detected in the lower limbs of preoperative patients. METHODS: Of 1,087
      patients scheduled for surgery from January to June 2002, US was performed in 85
      patients with a history of thromboembolism, a presence of abnormality in the
      lower extremities, or prolonged bed rest. RESULTS: In five patients thrombi were
      detected by US, but not in patients with a history of thromboembolism. To prevent
      pulmonary thromboembolism, prophylactic treatments were performed in 5 patients
      with DVT complications. CONCLUSIONS: We conclude that US should be performed on
      the preoperative patients with a presence of abnormality in the lower extremities
      or those who have had prolonged bed rest.

PMID- 15717464
TI  - [Evaluation of facial nerve palsy with electrogustometry and stapedial reflex].
AB  - BACKGROUND: To clarify the prognosis of facial nerve palsy, electroneuronal
      tests, including electrogustometry and stapedial reflex, have been utilized. But,
      the relationship among these tests and patients' prognosis is not clear. METHODS:
      Sixty five patients with peripheral facial nerve palsy were investigated.
      Electrogustometry (EG), stapedial reflex (SR) and blink reflex (BR) were
      performed at the first visit on the consult of facial nerve palsy. The palsy
      scale (full score is 100 points) was evaluated 8 weeks after the onset, and we
      defined cure cases if score became over 90 points. The cure ratio was examined on
      each group of EG positive or negative, SR positive or negative and BR R1 wave
      positive or negative, respectively. The relationship among these three
      examinations was also investigated. RESULTS: There were no significant
      differences between the cure ratio of EG positive and negative groups. However,
      the cure ratio of SR positive group was significantly larger than that of SR
      negative group. The cure ratio of BR positive group was 100%, regardless of the
      result of other two tests. CONCLUSIONS: The present study suggests that SR is a
      more useful parameter than EG for the evaluation of the prognosis of patients
      with facial nerve palsy, and the pathological meaning of these 2 tests is
      different from that of BR.

PMID- 15717465
TI  - [Anesthetic management of combined lung volume reduction surgery and off-pump
      coronary artery bypass grafting].
AB  - A 54-year-old man with severe emphysema and stenosis of coronary artery was
      scheduled for combined surgery of lung volume reduction and an off-pump coronary
      artery bypass grafting. His FEV1.0 was 600 ml and %FEV1.0 was 18%. Coronary
      angiography showed 99% stenosis of the left anterior descending artery.
      Anesthesia was induced with propofol, fentanyl and vecuronium, and was maintained
      with sevoflurane and continuous epidural anesthesia. In order to avoid high
      airway pressure, a pressure-controlled ventilation (less than 15 cmH2O) was
      carried out. A laryngeal mask airway was replaced with an endotracheal tube after
      surgery to avoid bucking during extubation, and this was removed after recovery
      from anesthesia successfully. No complications were observed during anesthesia.
      Lung volume reduction surgery after coronary reconstruction by off-pump coronary
      artery bypass grafting may be beneficial for patients with emphysema and ischemic
      heart disease.

PMID- 15717466
TI  - [Difficult airway management during emergency tracheostomy in a patient with
      severe rheumatoid arthritis].
AB  - We experienced difficult airway management in a 65-year-old woman with acute
      dyspnea due to bilateral recurrent nerve palsy suffering from severe rheumatoid
      arthritis for fifty years. Her cervical spine was ankylosed and could not be
      extended at all. Tracheostomy was planned under local anesthesia because of
      difficulty of endotracheal intubation, possibility of airway obstruction and
      laryngeal edema. In this condition, the surgical area was narrow and difficult to
      approach. The surgical bleeding and blood-aspiration into the tracheostomy site
      occurred followed by airway obstruction. A rigid tracheal tube could not be
      inserted through the tracheal incision and SpO2 decreased to 81%. We inserted a
      percutaneous cricothyroidotomy cannula through the tracheal incision and
      superimposed HFJV on her spontaneous ventilation. Assisting the ventilation in
      this way finally, a spiral endtracheal tube was inserted and her oxygenation
      became stable.

PMID- 15717467
TI  - [Anesthesia for a pediatric patient with Coffin-Siris syndrome].
AB  - A 3-year-old boy with Coffin-Siris syndrome was scheduled to undergo diagnostic
      laparoscopy, inguinal herniorrhaphy and orchiopexy at an ambulatory setting and
      same-day admission. Following anesthesia induction with inhalational sevoflurane,
      upper airway obstruction and hypoxemia developed. Hypoxemia was resolved
      immediately by manual positive pressure ventilation, although the stomach became
      bulged. Operation was finished uneventfully. However, he had massive bronchial
      secretion during anesthesia. He was admitted as planned and discharged on
      postoperative day 2. Since patients with Coffin-Siris syndrome have potential
      airway and pulmonary dysfunctions, careful perianesthesia airway and respiratory
      managements are essential.

PMID- 15717468
TI  - [Case of premature ventricular contraction immediately after electroconvulsive
      therapy in a depressive patient].
AB  - A 42-year-old woman with eating disorder underwent electroconvulsive therapy
      (ECT) under general anesthesia with thiamylal 150 mg and suxamethonium 60 mg. On
      her fourth ECT procedure, premature ventricular contraction (PVC) occurred
      immediately after the treatment. We speculate that increased release of
      catecholamine by ECT and hypokalemia caused PVC. It seems that she repeated self
      vomiting, because she had hypokalemia, metabolic alkalosis, and weight loss of 3
      kg in two weeks before arrhythmia episode. We conclude that in the anesthetic
      management of patients undergoing ECT a careful attention should be given to body
      weight change and serum electrolyte care before ECT because it is easy to develop
      electrolyte abnormality by eating disorder of self-emetic type.

PMID- 15717469
TI  - [Central hyperthermia suspected of malignant hyperthermia in a patient undergoing
      radical neck clipping for cerebral aneurysm].
AB  - A 45-year-old woman underwent radical neck clipping for cerebral aneurysm under
      isoflurane anesthesia. Her preoperative examination revealed elevated body
      temperature which had been normal on admission. Her body temperature increased up
      to 40.3 degrees C during anesthesia and surgery, and it showed a downward trend
      at the end of surgery. Malignant hyperthermia was excluded because the patient
      did not have metabolic acidosis, hypercarbia, hyperpotassemia or abnormal
      sweating anesthesia. The patient received intravenous dantrolene postoperatively
      since there was a suspicion of malignant hyperthermia on the basis of
      hyperthermia and increases in serum creatine kinase (CK) and myoglobin (Mb)
      levels. Her body temperature and serum CK and Mb levels decreased for a while
      after administration of dantrolene, but they increased again thereafter. The
      patient was aggressively cooled with a cooling blanket and hyperthermia and
      increases in serum CK and Mb levels disappeared in postoperative two weeks. She
      was discharged on foot without any neurological deficit on the forty-third
      hospital day. According to the diagnostic criteria for malignant hyperthermia by
      Larach and his colleague, malignant hyperthermia was somewhat less than likely in
      our case. The clinical course of the patient also suggested that a possibility of
      malignant hyperthermia was considerably low. The authors conclude that
      perioperative hyperthermia in our case must have derived from central
      hyperthermia following subarachnoid hemorrhage, and that postoperative increases
      in serum CK and Mb levels might have resulted from acceleration of sympathetic
      nervous system by subarachnoid hemorrhage.

PMID- 15717470
TI  - [Acute myocardial infarction due to coronary artery spasm after caesarean
      section].
AB  - We experienced acute myocardial infarction due to coronary artery spasm after
      caesarean section. A 41-year-old multigravida woman with no previous cardiac
      history or coronary risk factor developed acute myocardial infarction after
      caesarean section, and was successfully resuscitated with emergency percutaneous
      transluminal coronary angioplasty. Acute myocardial infarction during pregnancy
      and postpartum period is a rare event, but could be associated with high
      mortality if it occurs. It is necessary to consider the possibility of acute
      myocardial infarction and provide early diagnosis and treatment by
      multidisciplinary team when a pregnant woman complains of retrosternal chest
      pain.

PMID- 15717471
TI  - [Two episodes of cardiac arrest in a boy receiving sclerotherapy with polydocanol
      -a case report].
AB  - A 4-year-old boy, weighing 15.6 kg, experienced two episodes of cardiac arrest
      during the eight sessions of sclerotherapy under general anesthesia. Although
      cardiac arrest had been documented after accidental extubation during the seventh
      procedure, the specific cause had not been identified. For the eighth procedure,
      anesthesia was again induced and maintained with nitrous oxide and sevoflurane. A
      total of 10 ml of 3% polydocanol was injected. Approximately five minutes after
      the injection, his heart rate slowed and asystole developed. External cardiac
      massage was started immediately and atropine was injected intravenously. His
      heart started to beat again very soon. From the clinical course, the two episodes
      of cardiac arrest could be attributable to polydocanol overdose. It was concluded
      that severe circulatory derangement might follow an injection of polydocanol
      during sclerotherapy.

PMID- 15717472
TI  - [Alteration of education programs for anesthesia after the start of the
      obligatory postgraduate clinical training in Japan: survey at affiliated teaching
      hospitals of medical schools].
AB  - BACKGROUND: There is little information on education programs for anesthesia
      evaluating the present educational contents of early postgraduate clinical
      training period. METHODS: A questionnaire that consisted of 40 questions graded
      from 1 (absolutely unnecessary) to 5 (absolutely necessary) was send to 80
      medical universities in Japan to investigate the alterations of education
      programs for anesthesia at their affiliated teaching hospitals after the start of
      the obligatory early postgraduate clinical training. RESULTS: Answers were
      obtained from 59 of 80 universities (74%). Educational necessities after the
      obligation were significantly reduced at the following items compared with pre
      obligation; intravenous anesthesia technique (P<0.05), epidural (P<0.01) and
      spinal (P<0.05) anesthesia technique, anesthesia for cesarean section (P<0.01),
      and adult patients of more than ASA PS 3 (P<0.01) and pediatric patients
      (P<0.05). Contrarily, educational necessities increased significantly in the
      attending (P<0.01) and presentation (P<0.05) at the academic meetings.
      CONCLUSIONS: Clinical anesthesia education after the obligation was likely to
      change the direction to establish the safer anesthesia in patients with low
      anesthetic risk(s) along with encouraging the trainees to be interested in
      medicine.

PMID- 15717473
TI  - [Evaluation of our manual for prevention of perioperative pulmonary embolism].
AB  - All patients scheduled for surgical procedures were divided into three groups
      depending on risk grade for pulmonary embolism (PE) in our hospital from August,
      2001. Based on our experience of two PE cases after gynecologic surgery, we
      introduced the perioperative manual for prevention of PE from April, 2003.
      According to the manual criteria, we could decide indications for the physical
      prophylaxis or anticoagulant preventive treatment for the patients. In spite of
      introduction of the manual, two cases of PE occurred after femoral head
      prosthetic replacement for femoral head fracture patients classified low risk
      group in our criteria. The Japanese guideline for prevention of venous
      thromboembolism was published in January, 2004, but even low risk group patients
      were candidates for PE depending on the surgery and the situation. Even after
      installation of the guideline for PE, careful perioperative examination is
      mandatory to prevent and treat PE.

PMID- 15717474
TI  - [Questionnaire survey about an anesthesia information sheet].
AB  - BACKGROUND: The anesthesia information sheet used in our hospital describes the
      anesthetic management and complications in a simple style. Patients scheduled for
      operations receive it from their doctor with some explanation about anesthesia.
      The written informed consent on the sheet is obtained from the patients. METHODS:
      One hundred and one patients undergoing elective operations were interviewed
      after receiving explanations during the anesthesiologist's preoperative rounds.
      RESULTS: From this survey, 85% of the patients read it before the
      anesthesiologist's preoperative rounds and 75% of them understood the contents.
      After the anesthesiologist's explanation, 94% of the patients who had read it
      understood enough. About a third of the patients who had read the information
      sheet had anxiety about anesthesia. After the anesthesiologist's explanation, the
      percentage of patients who had anxiety decreased to 8%. 98% of the patients who
      read the information sheet answered that it should be read before the
      anesthesiologist's preoperative rounds. CONCLUSIONS: In view of this survey we
      concluded that reading the information sheet before the anesthesiologist's
      preoperative rounds is useful to increase the patients understanding of
      anesthesia.

PMID- 15717476
TI  - [Study of Streptococcus pneumoniae bacteremia in children].
AB  - From July 1999 to June 2004, we evaluated Streptococcus pneumoniae bacteremia in
      40 children in Kamikawa and Soya Subprefectures in Hokkaido by obtaining the
      patient's information from 7 out of 9 hospitals in the area. The incidences of S.
      pneumoniae bacteremia in children aged < 2 years and < 5 years were 79.1 and
      63.4. Median age was 19.6 months with a range from 4 months to 4 years. Thirty
      one (77.5%) of the total were less than 2 years old. All of the children were
      admitted. The diagnoses were occult bacteremia in 12 patients, pneumonia or
      bronchitis in 11, pharyngitis in 7, pneumonia and acute otitis media in 5, acute
      otitis media in 3, orbital cellulitis in 1, and arthritis in 1. All of the
      patients had fever and temperatures and 35 (87.5%) of them were more than 39
      degrees C. Ten patients had a febrile convulsion. Twenty-nine had a high total
      white blood cell counts (> 15,000/microg/ml) and 31 had positive CRP values (>
      0.6 mg/dl) on admission. Meningitis and poor prognosis did not occur after occult
      bacteremia in our patients. We studied the susceptibility to penicillin G in 22
      strains of S. pneumoniae isolated from the children. One and 18 strains were
      penicillin-resistant (MIC > or = 2.0 microg/ml) and intermediate (MIC 0.1-1.0
      microg/ml).

PMID- 15717475
TI  - [Supplemental survey in 2003 concerning life-threatening hemorrhagic events in
      the operating room].
AB  - BACKGROUND: We previously showed that pre-operative hemorrhagic shock and
      surgical hemorrhage were the major causes of life-threatening events in the
      operating room and subsequent fatality. We investigated the background of these
      events. METHODS: The Subcommittee on Surveillance of Anesthesia-Related Critical
      Incidents, Japanese Society of Anesthesiologist (JSA) sent confidential
      questionnaires to all JSA-certified training hospitals (n=862). The
      questionnaires were composed of two parts: one for examining all life-threatening
      events in the operating room and the other for examining the background of
      massive hemorrhage in the operating room. The number of patients registered
      between January 1, 2003 and December 31, 2003 was 1,367,790 from 782 hospitals.
      Life-threatening hemorrhagic events were reported in 1,011 patients, of whom 876
      patients were available for further analysis of the background of the events.
      Fatality within 7 postoperative days following these events was 45.4%. RESULTS:
      In patients who developed life-threatening events due to hemorrhage, 35.2% had
      blood loss of more than 12 l x 60 kg(-1) of body weight, 44.9% had a maximal
      hemorrhagic speed of more than 240 ml x min(-1) x 60 kg(-1) of body weight, and
      39.1% had a minimal hemoglobin concentration of less than 5 g x dl(-1). The main
      sources of hemorrhage were as follows: the abdominal aorta, 15.4%; the thoracic
      aorta, 14.0%; the liver, 12.6%; intra-cranium, 8.2%; the pelvic organs, 8.0%;
      celiac or mesenteric artery, 7.8%; the lung, 7.1%. Of patients who developed life
      threatening events due to preoperative hemorrhagic shock, 18.3% underwent cardiac
      massage preoperatively, 50.0% lost consciousness, 58.5% were intubated, and 16.4%
      were retrospectively judged to have had no operative indications. Human factors
      also affected the life-threatening events due to preoperative hemorrhagic shock:
      delayed decision making concerning indications for surgical treatment, 15.6%;
      delayed admission to the operating room, 16.6%; delayed supply of blood products,
      25.5%; problems in surgical management, 16.3%; problems in anesthetic management,
      28.1%. These problems in anesthetic management included shortage of supportive
      anesthesiologists. This was partly explained by the time of their admission to
      the operating room: 67.0% of the patients admitted during the week end or at
      night. Of the patients who developed life-threatening events due to surgical
      hemorrhage, 58.0% were predicted preoperatively to develop massive hemorrhage by
      anesthesiologists, and 66.7% were informed of the risks of massive hemorrhage and
      associated complications. The main causes of surgical hemorrhage were as follows:
      adhesion or invasion, 44.7%; and problems in surgical judgments or techniques,
      43.7%. Anesthetic management affected the development of life-threatening events
      in these patients: lack of infusion prior to hemorrhage, shortage of supportive
      anesthesiologists, delay in ordering additional blood products, delayed judgment
      to start blood transfusion, and shortage of rapid infusion/transfusion apparatus.
      Delay for hospitals in obtaining blood supply from blood banks was reported in
      13.0% of cases, and delayed supply from inhospital blood transfusion service to
      the operating room in 16.0%. Despite massive hemorrhage, ABO cross-matching was
      omitted only in 13.4% of patients, and transfusion of ABO-compatible, instead of
      ABO-identical red blood cells, was performed only in 1.3%. CONCLUSIONS: To reduce
      life-threatening hemorrhagic events in the operating theater, reorganization of
      emergency medical service and blood supply, improvement of surgical techniques,
      improved triage of patients with hemorrhagic shock, flexible application of
      compatible blood products in emergency situations, and improvement of the quality
      and number of anesthesiologists should be considered.

PMID- 15717477
TI  - [Cumulative vaccination coverage of measles- and oral polio vaccine obtained by
      the nationwide survey].
AB  - In 2002 we estimated the measles cumulative vaccination coverage (CVC) in Japan
      by randomly selecting a total of 5,000 3-year-old children from the total
      Japanese population and examining the age in months when they were vaccinated
      against measles. This survey revealed that in Japan measles CVC at ages 18, 24,
      and 36 months were 61.7 +/- 1.6%, 79.6 +/- 1.3%, and 86.9 +/- 1.1%, respectively.
      The results obtained in 2003 revealed that the measles CVC among 3-year-old
      children in 2003 was higher than that obtained in 2002, with especially
      noticeable improvement in their period of 12 to 23 months of age. It is estimated
      that this improvement was attributed to the effort made by many persons
      concerning vaccination to raise the vaccination rate. In 2003 oral polio vaccine
      (OPV) CVC was investigated for the first time, in addition to measles CVC. OPV
      CVC of the first dose at 6, 12, and 36 months of age were 44.2 +/- 1.5%, 85.5 +/-
      1.1%, and 94.7 +/- 0.8%, respectively. The results of the second dose at 12, 18,
      and 36 months of age were 42.3 +/- 1.5%, 73.5 +/- 1.3%, and 90.7 +/- 0.9%,
      respectively. Even at 36 months of age the CVC level of the second dose of OPV
      was found to be slightly lower than that of the first dose.

PMID- 15717478
TI  - [Usefulness of urinary antigen and sputum Gram stain for rapid diagnosis of
      pneumococcal respiratory infections].
AB  - We evaluated the usefulness of a rapid urinary antigen detection kit (Binax NOW)
      to detect Streptococcus pneumoniae in the early diagnosis of pneumococcal
      respiratory tract infections in 313 patients with presumptive respiratory tract
      infections. We compared results of this test with those of sputum Gram staining.
      Urinary antigen and sputum Gram staining were respectively positive in 37 and 36
      of 57 patients with pneumococcal respiratory infections. The urinary antigen
      showed moderate positive rate of 64.9% and low false positive rate of 2.3%. The
      sputum Gram staining also showed moderate positive rate of 64.3% and low false
      positive rate of 3.5%. Pneumococcal antigen was more frequently detected in
      patients with severe pneumococcal infections (6/6) than those with mild (5/10)
      and moderate (26/41) infections. Of the 9 patients who had received antibiotics
      before testing, antigen was detected in 8 but positive results of sputum Gram
      stain were in 4. In conclusion, urinary antigen test is a useful test for early
      diagnosis of pneumococcal respiratory infections especially in adult patients
      with moderate or severe infections for whom demonstrative results of a sputum
      Gram stain is unavailable, even after commencement of antibiotic treatment.

PMID- 15717479
TI  - [Antifungal susceptibility of Candida species causing candidemia in Kurume
      University Hospital and Shaiseikai Hutukaichi Hospital].
AB  - Prevention of candidemia has been difficult and empirical therapy may eventually
      reduce morbidity and mortality. Successful empirical therapies depend on
      understanding of fungal features and antifungal agents. Susceptibility to
      amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), itraconazole
      (ITCZ), miconazole (MCZ), and micafungin (MCFG) of 41 Candida species isolated
      from blood were determined. Candida albicans was the most common species (23
      species), followed by C. parapsilosis (5 species), C. tropicalis (4 species), C.
      glabrata (3 species), C. guilliermondii (2 species), C. krusei (1 specie), and
      Candida spp (3 species). The isolation rates of the drug-resistant (DR) fungi
      were 5% for 5-FC. The rates of DR and susceptible dose dependent (S-DD) fungi
      were 0% and 2% for FLCZ, respectively. The rates of DR and S-DD fungi were 0% and
      17% for ITCZ, respectively. No shift to resistant species in C. albicans occurred
      in our hospitals. All C. albicans were susceptible for the antifungal agents
      examined.

PMID- 15717480
TI  - [A survival case of tetanus complicated with disseminated intravascular
      coagulation syndrome in the elderly, rescued by mechanical ventilation and
      administration of thiamylal].
AB  - A 78-year-old Japanese female was admitted to our hospital because of headache.
      Trismus, opisthotonus and convulsion appeared in the early morning on the second
      hospital day. She was diagnosed as tetanus based on these symptoms and the
      history of trauma on her left hand 6 days ago. A piece of bamboo was extracted
      from her left hand. However, Clostridium tetani was not identified. Thiamylal and
      mechanical ventilation were initiated combined with Pancronium, Diazepam and
      tetanus immune globulin. Gabexate Mesilate was also added for disseminated
      intravascular coagulation syndrome probably associated with rhabdomyolysis. By
      these treatments, she was healed leaving only a disuse syndrome of her limbs.

PMID- 15717481
TI  - [Evaluation of immunochromatography test for rapid detection of influenza A and B
      viruses].

PMID- 15717482
TI  - Health-related quality of life in outpatients of a psychosomatic medicine clinic:
      a pilot survey in Japan.
AB  - The objective of this study is to clarify the difference of health-related
      quality of life (HRQoL) profiles by disease category with the SF-36
      questionnaires, and to examine the possibility of application for a longitudinal
      study. A number of subjects was 536, specifically 127 men and 409 women. For all
      of the eight domains, Cronbach's alpha exceeded 0.7. Categories in which all of
      the domains were approximately equal to the national standard included
      hypertension, neck and shoulders syndrome, diabetes, hyperlipidemia and cardiac
      disease. Bodily pain was especially lower in gastrointestinal disorder,
      spondylopathy and hemopathy. Patients with mental disorder had lower scores in
      all domains. Categories in which 5-7 of the eight domains had lower scores
      included arthropathy, asthma, chronic hepatitis, autonomic imbalance,
      'ovariopathy and hysteropathy' and chronic rheumatism. No significant change was
      found between the first and second scores in hypertension as a representative of
      the high HRQoL categories. In mental disorder as a representative of the low
      HRQoL categories, however, five of the eight domains increased significantly. We
      concluded that a target disease should be chosen among subjects with low HRQoL
      scores before an intervention to assess its effectiveness. Or subjects with high
      HRQoL scores can be examined to determine whether they keep the same level of
      HRQoL.

PMID- 15717483
TI  - Parasympathetic neural control of canine tracheal smooth muscle.
AB  - The middle segment of the trachea is innervated by the recurrent laryngeal and
      pararecurrent nerves. This study determined the pathway that mediated descending
      commands to the tracheal smooth muscle. Animals used were seven paralyzed and
      tracheostomized dogs. Tracheal contraction induced either by apnea, mechanical
      stimulation of the tracheal bifurcation or hypercapnia was always composed of
      tonic and rhythmic components. The rhythmic contraction developed in synchrony
      with rhythmic bursts on phrenic nerve activity (PNA). The respiratory-related
      bursts were also observed on the recurrent laryngeal nerve activity (RNA) and
      pararecurrent nerve activity (ParaRNA). During apnea there was no tonic activity
      neither on RNA or PNA, whereas ParaRNA had both tonic and rhythmic activities.
      Bursts on RNA preceded to correspondent PNA-bursts by 90+/-13 ms. In contrast,
      ParaRNA-burst always developed later than PNA-burst and it started at almost the
      same time as that of tracheal rhythmic contraction. During mechanical stimulation
      of the trachea or CO2-loading, though RNA did not include tonic component,
      ParaRNA had tonic activity during tracheal tonic contraction. These findings
      suggested that rhythmic and tonic contractions of the trachea were mediated
      through the pararecurrent nerve but not through the recurrent laryngeal nerve.

PMID- 15717484
TI  - A case of the diaphragmatic flutter with an electromyographic study of the
      respiratory muscles.
AB  - A 28-year-old female was complained with dyspnea and involuntary rhythmic
      movements in her chest and upper abdomen. Diagnosis of the diaphragmatic flutter
      was established since high frequency intermittent discharges of the respiratory
      muscles superimposed on her ordinary respiratory activities. The origin of these
      abnormal discharges may be in the central nervous system and the psychosomatic
      factor is participating in the development of the diaphragmatic flutter.

PMID- 15717485
TI  - A case report: spontaneous rupture of dissecting aneurysm of the middle colic
      artery.
AB  - Aneurysms of the superior mesenteric artery branches are rarely reported, even
      among them colic artery aneurysms are seldom. We report a case of 78-year-old
      male with ruptured dissecting aneurysm of middle colic artery. The patient
      complained abdominal pain and nausea during hospital stay for renal stone. The
      patient suddenly developed severe abdominal pain, leading to shock. He underwent
      emergency surgery under a preoperative diagnosis of intraperitoneal hemorrhage.
      At exploratory laparotomy, a large hematoma involving the mesentery root of the
      transverse colon was associated with a ruptured aneurysm measuring 15 x 10 mm in
      size, which was located to the mid-portion of middle colic artery. Right
      hemicolectomy was carried out because of ischemic changes in the ascending colon.
      Histological examination demonstrated a ruptured dissecting aneurysm of the
      middle colic artery approximately 5 cm in length, associated with destruction of
      the tunica interna and media. The aneurysm was thought to result from idiopathic
      segmental arterial mediolysis, because no definitive evidence of atherosclerosis
      or arteritis was observed.

PMID- 15717486
TI  - A case of primary small intestinal cancer diagnosed by laparoscopy.
AB  - The patient was a 61-year-old female who developed ileus. Physical findings
      showed abdominal distension but peritoneal irritation signs were not observed.
      After the conservative treatment by the ileus tube, encircling stenosis was
      observed in the jejunum at about 50 cm on the anal side from the Treitz ligament
      on contrast radiography of the small intestine through the ileus tube. Tumor
      markers were normal except for mild elevation of IL2-R (609 U/ml). After
      confirming sufficient bowel decompression and the absence of other lesions,
      surgery was performed based on a preoperative diagnosis of small intestinal tumor
      including adhesive ileus, GIST, or malignant lymphoma. First, under the
      laparoscopic observation, the lesion was resected and definitive diagnosis was
      established as primary moderately to poorly differentiated adenocarcinoma of the
      small intestine by rapid intraoperative pathological diagnosis. Then, extensive
      jejunal resection involving sufficient lymph node dissection was performed as
      open surgery. Radical surgery was successfully performed.

PMID- 15717487
TI  - Squamous cell metaplasia in the rectum: a case report and review of the medical
      literature.
AB  - Squamous cell metaplasia of colorectal epithelium is very rare. There have been
      only 29 cases previously reported in the English language medical literature. The
      cause and consequences of squamous cell metaplasia in the colorectum are unknown.
      We encountered a patient with squamous cell metaplasia in rectum who have had a
      curious history for more than 20 years. This case may be useful in attempting to
      understand the pathogenesis of squamous cell metaplasia in colorectum.

PMID- 15717488
TI  - A method to accurately inject tumor cells into the caudate/putamen nuclei of the
      mouse brain.
AB  - OBJECTIVE: To improve currently used techniques to implant tumor cells into the
      parenchyma of the mouse brain. MATERIALS AND METHODS: The stereotactic injection
      of 0.5 to 5 microl of indigo carmine over 5 to 40 minutes into the
      caudate/putamen nuclei of the mouse was done followed by sacrifice and
      examination of the brain injection site. 1 microl containing 10(5) U87MG glioma
      cells were stereotactically implanted into the caudate/ putamen nuclei over 20
      minutes. The animals were sacrificed from one hour to 63 days after implantation
      and the brain examined and tumor size measured. RESULTS: An injection of 1 microl
      of indigo carmine over 20 minutes produced a spherical deposit of dye within the
      caudate/putamen nuclei. Larger volumes of indigo carmine or shorter injection
      times resulted in dye spreading along the injection tract or into the ventricles
      or subarachnoid space. Using the results of the dye studies, the same parameters
      were used to successfully inject and confine the glioma cells to the
      caudate/putamen nuclei in 30 of 32 mice. No tumor was found in 2 animals and
      appears to be explained by obstruction of the injection cannula. The tumor cells
      appeared viable an hour after injection. However by day three, considerable
      necrosis of tumor cells were noted, the effects of which resolved by day five. On
      day six, the injection site was comparable to that at one hour. In the early
      phase, until the fifth week, tumor volume doubling time was ten days while
      afterward it was only five days. CONCLUSION: The technique described allows the
      highly accurate and reproducible introduction of a given number of cells into a
      specific area of the mouse brain. This should reduce the intragroup variability,
      be it control or therapeutic, allowing better assessment of outcome with fewer
      number of mice.

PMID- 15717489
TI  - Differences in penetration force of intravenous catheters: effect of grinding
      methods on inner needles of intravenous catheters.
AB  - OBJECTIVES: To compare penetration forces of intravenous catheters based on two
      grinding methods used for the inner needle tip. METHOD: Forty intravenous
      catheters were divided into two groups according to two inner needle grinding
      methods: Lancet and Backcut. To compare the characteristics of inner needles, 18
      gauge Surflo outer catheters, were attached to all inner needles. We measured
      penetration forces by attaching a "Push-Pull-Gauge" to the chamber of intravenous
      catheters, then we penetrated intravenous catheters through a 0.04-mm thick
      polyethylene film. The penetration velocity was 3.3 mm/sec. we measured
      penetration forces at 30- and 45-degree penetration angles. RESULTS: There was no
      significant difference in the penetration forces of inner needle and outer
      catheter between the two groups at the 45-degree penetration angle. Penetration
      forces of the inner needle and the outer catheter in the Backcut group was
      significantly lower than those of the Lancet group at the 30-degree penetration
      angle. The penetration force of the outer catheter was reduced from 0.3 N to 0.18
      N, a 40 % reduction at 30-degree penetration angle. Computerized measurements of
      penetration holes indicate that the Y-shaped incision mark of the Backcut leaves
      larger incision hole than the actual puncture size. We hypothesize that the Y
      shaped incision mark creates more efficient path for the outer catheter to
      advance. Therefore, lower penetration force was indicated compared to the other
      group. CONCLUSION: Backcut shows less penetration force of inner needles of
      peripheral intravenous catheters than lancet.

PMID- 15717490
TI  - Preservation of tubal function following methotrexate treatment for ectopic
      pregnancy.
AB  - To evaluate methotrexate (MTX) administration as a conservative treatment for
      ectopic pregnancy, we reviewed the medical records of 248 cases (210 patients) of
      MTX treatment for tubal pregnancies at our department between December 1985 and
      December 2003, and compared its pregnancy prognosis with that of laparoscopic
      salpigotomy (59 patients). With the MTX treatment, 185 patients were successfully
      treated, and the subsequent pregnancy rate and ectopic pregnancy rate were 48.4 %
      and 18.4 %, respectively, while those rates were 49.2 % and 18.6 %, respectively,
      after the salpigotomy. These results suggest that MTX treatment is comparable to
      the more conservative operation. To clarify the (dys/) function of the ectopic
      implantation tubes and MTX-treated tube (s), we excluded patients who had a
      contra-lateral healthy tube, and extracted 40 patients as "the affected tube
      group", where the pregnancy-related parameters were not adversely affected. The
      findings suggest that MTX is not necessary to preserve tubal function.

PMID- 15717491
TI  - Abnormality of energy metabolism in the skeletal muscle of patients with liver
      cirrhosis and changes under administration of glucose and branched-chain amino
      acids.
AB  - We assessed changes in skeletal muscle energy metabolism by 31P-magnetic
      resonance spectroscopy (31P-MRS) and oxygen supply by near-infrared spectroscopy
      (NIR), after exercise and after administration of glucose and a branched-chain
      amino acids (BCAA), in healthy volunteers and patients with liver cirrhosis. As
      for the patients with liver cirrhosis, 4 were classified in Child-Pugh Grade A
      and the other 4 in Grade B. In patients with liver cirrhosis, the intramuscular
      pH and PCr index (PCr/PCr + Pi) were lower than in healthy subjects after
      exercise in the fasting state; the deltapH and deltaPCr index were statistically
      siginificant (p<0.05), indicating a disorder of aerobic metabolism. NIR revealed
      normality with oxygen supply and suggested a decreased oxygen utilization
      efficiency; that is, failure of the TCA cycle. The deltapH improved slightly
      after the administration of glucose alone, while it was definitely low (p<0.05)
      after co-administration of glucose and BCAA, which acts directly on the TCA
      cycle, indicating improvement of skeletal muscle energy metabolism.

PMID- 15717492
TI  - Spontaneous conception after ten years of infertility, giving up in-vitro
      fertilization (IVF) treatments, adoption of a child and two ovarian pregnancies:
      a case report.

PMID- 15717493
TI  - [Brain science in emotional memory: role of the hippocampus].

PMID- 15717494
TI  - [HB-EGF is a promising target molecule for ovarian cancer].

PMID- 15717495
TI  - [Medical image analysis--image guided medicine].
AB  - Recent progress of our group on medical image analysis research and its
      application to image guided medicine is presented. Firstly, we describe
      preoperative image analysis for organ modeling and automated surgical planning.
      Secondly, newly developed calibration technologies for intraoperative guidance of
      endoscopic surgery are presented.

PMID- 15717496
TI  - Unstable hemoglobinemia, Hb Buenos Aires, Bryn Mawr, followed up for eighteen
      years.
AB  - A 20-year-old man has been under observation for 18 years because of unstable
      hemoglobinemia, Hb Buenos Aires, Bryn Mawr (beta-globin, Phe85Ser). At the age of
      19 years, he was hospitalized because of fever and hemolytic crisis, and the
      symptoms resolved after infusion of antibiotics. Nucleotide sequencing of the
      beta-globin gene confirmed that the patient was heterozygous for the mutation.
      The patient's erythrocytes showed an increased affinity for oxygen and a
      prolonged glycerol lysis time. We review a previously reported single family and
      5 other cases, and discuss the clinical significance of splenectomy and plasma
      derived haptoglobin.

PMID- 15717497
TI  - Watching and learning.

PMID- 15717498
TI  - Continuing care confusion.

PMID- 15717499
TI  - Power to the people.

PMID- 15717500
TI  - A framework to promote the holistic assessment of older people in emergency care.

PMID- 15717502
TI  - Implementing a best practice statement in nutrition for frail older people: Part
      1.

PMID- 15717501
TI  - The Osteoporosis Nurse Initiative: past, present and future.

PMID- 15717503
TI  - Older people with learning disabilities. Part 1: Individuals, ageing and health.
AB  - In a two-part article, Robert Jenkins considers how nursing care needs to develop
      in order to support the growing numbers of people with learning disabilities who
      are living into older age. Here, he looks at definitions, health issues and
      nursing needs.

PMID- 15717504
TI  - Promoting oral hygiene.

PMID- 15717506
TI  - Building a link.

PMID- 15717507
TI  - Nursing older donkeys.

PMID- 15717508
TI  - [Choice of the parameters of artificial ventilation in patients with acute
      respiratory distress syndrome].
AB  - The paper presents the results of use of two modes of controlled artificial
      ventilation (ALV) in adult patients with acute respiratory distress syndrome of
      various genesis: 1) ALV with its controlled volume, the descending pattern of
      inspiratory flow, the limitation of respiratory volume in the airways (RV, 6-8
      ml/kg; Ptr.peak < 30 cm H2O), 2) ALV with its controlled volume, the orthogonal
      pattern of inspiratory flow (RV, 12-15 ml/kg, Ptr.peak > 35 cm H2O). It also
      shows the advantages and disadvantages of these respiratory procedures in this
      group of patients.

PMID- 15717509
TI  - [Kinetic therapy for acute respiratory distress syndrome].
AB  - The authors evaluated the clinical and physiological effects of kinetic therapy
      (KT) in the treatment of acute respiratory distress syndrome (ARDS). Forty-six
      patients with ARDS underwent successive postural positioning in accordance with
      two regimens: 1) lateral, prone, contralateral, supine positions; 2) prone,
      lateral, contralateral, supine positions. The criterion for changing each
      position was the change in monitoring indices: SpO2, PaO2, and thoracopulmonary
      compliance (C). KT was performed until a respirator was withdrawn from the
      patient. In 25 patients, each maneuver of positioning was made during 30-minute
      propofol sedation. The control group included 24 patients with ARDS who received
      neither KT nor propofol sedation. KT caused a decrease in Vd/Vt, Qs/Qt and an
      increase in PaO2/FiO2 and C was more intensive, as compared with the control
      group. The duration of the patient's prone position was 3.2-0.7 hours and that of
      the supine position was 3.4-0.8 hours. The right and left lateral positions
      lasted 1.1-0.2 and 1.3-0.2 hours, respectively. KT regimen 1 was found to be more
      effective than KT regimen 2. Propofol sedation enhanced the efficiency of KT. The
      latter reduced death rates in patients with ARDS.

PMID- 15717510
TI  - [The specific features of lipid metabolism and changes in the plasma activity of
      transaminases in patients with sepsis].
AB  - A parallel study of changes in the activity of transaminases and the parameters
      of lipid metabolism was conducted in patients with sepsis or septic shock,
      receiving renal replacement therapy. The multiple baseline increase in the
      activity of gamma-glutamyltranspeptidase was observed in about 50% of the
      patients and the elevated level of triglycerides and very low density-lipoprotein
      cholesterol in all the examinees. In case of the baseline multiple increased
      activity of gamma-glutamyltranspeptidase as compared with the normal
      physiological values, the probability of a good clinical outcome was some 67%, in
      the survivors, the activity of the enzyme significantly increasing during
      therapy. In the absence of the baseline multiple increased activity of gamma
      glutamyltranspeptidase, there was a good clinical outcome provided that there
      were positive changes in triglycerides and very low-density lipoprotein
      cholesterol during therapy and its probability was about 33%. It is concluded
      that the activity of gamma-glutamyltranspeptidase and the concentration of
      triglycerides and very low-density lipoprotein cholesterol may be used to
      evaluate the efficiency of treatment and as predictors of the outcome of
      treatment in patients with sepsis and septic shock.

PMID- 15717511
TI  - [Pharmacokinetic simulation of different modes of renal replacement therapy].
AB  - Based on the results of examination of patients with severe acute renal failure
      and multiorgan insufficiency, the authors give a comparative analysis of
      different modes of renal replacement therapy, such as intermittent
      hemofiltration, continuous arteriovenous hemofiltration, and continuous
      venovenous hemodiafiltration. Kinetic simulation in terms of urea and creatinine,
      by employing a one- and two-pool model for the disposition of these substances in
      the patient's body was taken as a basic method. The analysis led to the
      conclusion that continuous hemodiafiltration (CHDF) with an actually large volume
      of filtration and dialysis was the optimum technique for correcting uremic
      impairments of homeostasis in critically ill patients. CHDF failed to induce a
      significant metabolic stress and to noticeably affect the rate of urea and
      creatinine generation. Overall, all the filtration treatments are an effective
      means of eliminating low-molecular-weight nitrogenous metabolites that are
      characterized by the high rate of generation and the large volume of disposition
      in the organism. It is necessary only to correctly select a dose of renal
      therapy.

PMID- 15717512
TI  - [Hemostatic disorders in patients with pancreonecrosis at the stage of purulent
      complications].
AB  - The responses of blood coagulation and fibrinolysis show a clear phase course in
      patients with pancreonecrosis in the dynamics of the postresuscitation period.
      There were different changes in the phasic pattern of hemostatic disorders in
      survivors as compared with a group of deceased patients. With a good outcome,
      there was a twofold reduction in the concentration of fibrinogen as compared with
      the normal values and an increase in whole blood fibrinolytic activity on days 21
      23. The increased whole blood fibrinolytic activity in the group of survivors in
      the presence of invariably decreased Hageman-dependent plasma fibrinolytic
      activity in both groups of the patients suggests that formed blood cells
      contributes to the process of recovery.

PMID- 15717513
TI  - [Role of interleukin-2 in the treatment of patients with infective and
      inflammatory complications after surgery for acute ileus].

PMID- 15717514
TI  - [Hemofiltration as part of complex intensive therapy for acute lung lesion in
      patients with peritonitis].

PMID- 15717515
TI  - [Antithrombotic mechanisms in the acute period of severe brain injury].
AB  - Antithrombotic mechanisms were studied in 156 patients with severe brain injury
      (SBI) on days 1, 3, 5, 7, and 9 after injury. It was found that the acute period
      of SBI was marked by a reduction in the athrombogenic potential through both the
      consumption of physiological anticoagulants, antiaggregants, the components of
      the plasmin system and the elevated levels of fibrinolytic inhibitors. The
      inhibitory mechanism responsible for impaired fibrinolysis predominated when
      infectious complications of SBI developed.

PMID- 15717516
TI  - [Lesions of the vascular endothelium and impairments of haemostatic coagulation
      in patients with severe craniocerebral trauma].
AB  - Malfunctions of central hemostasis chains, activation of blood coagulation
      systems and decreased antithrombogenic potentials of vascular walls are typical
      of craniocerebral trauma at exacerbation. It provokes the onset of the DIC
      syndrome in 98.8% of examinees; the below signs are observed in such condition:
      decreased platelet resistance of vascular walls, increased aggregation activity
      of platelets, activated coagulation chain of hemostasis and increased blood
      viscosity. The prognostically unfavorable criteria of coagulopathy in acute
      craniocerebral trauma are as follows: pathological response of the vascular wall
      to transitory ischemia observed concurrently with a reduced dynamic FW activity;
      a persistently low and/or decreased dynamic AT-III activity; decreased
      fibrinolytic activities of plasma and platelet counts; and persistently higher
      concentrations and/or higher dynamic concentrations of fibrinogen and soluble
      fibrin mono-measured complexes (according to coagulation tests). Hemostasis
      should be corrected with respect to the above hemostasiologic syndromes.

PMID- 15717517
TI  - [Impaired blood coagulative properties in the early postresuscitation period and
      their prevention].
AB  - Experiments were conducted on 356 non-inbred albino rats that had experienced 8
      min clinical death caused by acute hemostasis or mechanical asphyxia.
      Irrespective of the cause of the clinical death, the authors identified uniform
      phase coagulative disturbances. They appeared as reactive hypercoagulation
      occurring during clinical death and progressing within 3 hours after
      resuscitation, by transforming to hypocoagulation that peaked at hours 6 to 24
      hours. On day 3, recurrent hypercoagulation developed. Dalargin and mildronate
      were found to prevent the activation of the vascular and thrombocytic links of
      hemostasis and the release of clotting agents.

PMID- 15717518
TI  - [Postpartum emergencies: some aspects].
AB  - The critical states occurring during pregnancy, labor, and early puerperium were
      analyzed. Seventy puerperas treated at intensive care units (ICU) were examined.
      The patients were divided into 5 groups: 1) those with preeclampsia (n = 15); 2)
      eclampsia (n = 22); 3) massive blood loss (n = 17); 4) pyoseptic complications (n
      = 10); 5) acute respiratory failure (n = 6). The APACHE II scale severity was 22
      +/- 5.3 scores. The mean age of puerperas is 29.2 +/- 7.2 years. Total mortality
      was 14.3%. Parametric and non-parametric statistic methods were used to analyze
      the reasons for referral of the patients to ICU, their age composition, the
      association of an outcome to the time of their referral to ICU, the duration of
      stay there and at hospital, mortality, the time of controlled ventilation, the
      incidence of multiorgan failure. The common reasons for referral of the puerperas
      from maternity homes to ICU were eclampsia, preeclampsia, and massive blood loss.
      Acute respiratory distress syndrome (52.9%), encephalopathy (44.3%), coma
      (47.1%), and intestinal insufficiency (38.6%) were predominant in the pattern of
      multiorgan failure in intensive care obstetric patients. When emergencies
      occurred in puerperas, earlier referral from maternal homes to ICU caused a
      reduction in mortality from 33.% at referral on day 3 after their occurrence to
      23.5% at referral on day 2, and to 11.5 at referral on day 1.

PMID- 15717519
TI  - [Use of the solutions of hydroxyethyl starch and reamberin in the combined
      treatment of severe gestosis].
AB  - The effects of the solutions of hydroethyl starch (HES) and reamberin on
      hemodynamics, metabolism, and water-sector disorders were studied in patients
      with severe gestosis. The study covered 42 puerperas who were divided into 3
      groups: 1) 10 patients with severe gestosis and normal acid-alkali balance (AAB);
      2) 10 with severe gestosis and metabolic acidosis; 3) 22 pueperas with
      physiological single pregnancy (a control group). Group 1 patients were given
      infusions of 6% HES solution, 5-6 ml/kg; Group 2 received in addition to 6% HES
      solution in the above dose infusions of 1.5% reamberin solution, 5 ml/kg. In
      patients with severe gestosis, hemodynamic, water-sector, and metabolic
      monitoring on puerperal days 1-5 were found to identify changes in oxygen supply
      and consumption, water balance, and AAB. In Group 1 patients, HES infusion on
      days 1-2 after delivery decreased the content of systemic water, extracellular
      and interstitial fluid, increased oxygen supply; in Group 2, combined infusion
      therapy with GES and reamberin on puerperal days 1-2 led to an increase in oxygen
      supply and consumption and a reduction in interstitial hyperhydration and to
      normalization of AAB.

PMID- 15717521
TI  - [Correction of hypoxic lesions of cerebral cortical neurones with blood
      substituting solutions in acute massive blood loss in the experiment].

PMID- 15717520
TI  - [Effects of perfluorane on delayed hypoperfusion after global transient ischemic
      attack].

PMID- 15717522
TI  - [Postresuscitation cerebral structural and functional changes associated with the
      initial type of behavior].
AB  - The elevated cross-shaped labyrinth test carried out on highly, moderately, and
      low active experimental animals revealed significant differences in the baseline
      density and composition of neuroglial populations of numerous formations of the
      brain, as well as in the early structural and functional sequels of experienced
      clinical death. The most pronounced postresuscitation abnormal changes were
      observed in highly active animals and the least marked ones were seen in
      moderately active animals.

PMID- 15717523
TI  - [High thoracic epidural analgesia in multimodality intensive care for acute
      coronary syndrome].

PMID- 15717524
TI  - [The surfactant system in adults with lung diseases].

PMID- 15717525
TI  - [Clinical significance of albumin parameters in oncology patients].
AB  - The paper contains modern data on the potentialities of determining the albumin
      parameters in clinical oncology. Finding of the total albumin concentration,
      effective albumin concentration, albumin binding reserve and toxicity index by
      using the K-35 fluorescence probe can be useful in diagnosing cancer, choosing a
      treatment scheme and in the course of treatment. The albumin parameters can be
      used, primarily, on a wide-scale basis in postoperative intensive care.

PMID- 15717526
TI  - [Serum albumin: properties and functions and their evaluation in emergencies].

PMID- 15717527
TI  - [Radon prophylaxis to reduce morbidity in population of the Russian Federation].

PMID- 15717528
TI  - [Combined rehabilitation treatment for seronegative spondylarthritis including
      novel non-pharmacological technologies].
AB  - The trial included 90 patients with seronegative spondylarthritis (SA): 60 ones
      with ankylosing spondylarthritis (30 with central and 30 with peripheral forms)
      and 30 patients with reactive arthritis (RA). RA patients with affection of the
      peripheral joints, periarticular tissues and the spine are effectively treated
      with a complex of water radon baths and low frequency ultrasound but in affection
      of the peripheral joints and tendon-ligament system water radon baths and
      ultraphonophoresis of hydrocortisone are recommended. Water radon baths and
      decimetric therapy are good for patients with central ankylosing spondylarthritis
      having a dominant lesion of the spine. In involvement of the joints and tendon
      ligament system it is recommended to use a complex of water radon baths and
      ultraphonophoresis of hydrocortisone.

PMID- 15717529
TI  - [Physical factors in rehabilitation treatment of patients with Ixodes tick-borne
      borreliosis with primary lesions of the joints].
AB  - The studies made in 96 patients suffering from chronic ixode tick borreliosis
      with a prevalent joint lesion justified two-stage treatment with physiotherapy at
      the second stage. The proposed therapy is well tolerated, produced a good
      improvement in 82.4% patients, the response persisting for 8.8 +/- 0.2 months vs
      5.6 +/- 1.0 months in the control group on pharmacotherapy alone.

PMID- 15717530
TI  - [Trends in variability of the central blood circulation in healthy individuals in
      response to massage of the collar cervical region].
AB  - Dynamics of slow wave variability of heart rate and left ventricular ejection
      fraction was studied in the course of 10-day course of collar region massage and
      that of zone related by reflex with circulation. It was found that such massage
      can produce changes in regulation of the above indices.

PMID- 15717531
TI  - [Changes in poststroke asthenia in the course of rehabilitation].
AB  - Questionnaire (asthenia MFI) survey of 2043 patients early in rehabilitation
      after ischemic stroke in the territory of the carotid arteries was made. Asthenia
      was detected in 81% patients with elevated total score, physical, psychic
      asthenia, hypoactivity and low motivation. Asthenia was secondary and correlated
      with social maladaptation. Rehabilitation in a specialized neurological
      department of health resort Ust-Kachka leads to positive changes in the above
      indices.

PMID- 15717533
TI  - [Efficacy of sulfate calcium mineral water in disorders of motor evacuatory
      function of the stomach and gallbladder].
AB  - Patients with disorders of motor-evacuatory gastric function and those of the
      gallbladder received sanatorium spa treatment with Nizhneivkinskaya 2K mineral
      water. It was found that both course and single intake of the above mineral water
      induce clinical remission of the disease, normalization of the echoscopic picture
      of the stomach and gallbladder, their motor function, tesiocrystalloscopic
      characteristics of the saliva. Therefore, spa treatment with mineral water
      Nizhneivkinskaya is effective in rehabilitation of patients with gastric and
      gallbladder motor-evacuatory dysfunction.

PMID- 15717532
TI  - [Effects of combined action of sapropel and magnetic field on hepatic function in
      modeling toxic hepatitis in various seasons].
AB  - Experiments on 172 Wistar rats modeled CCl4 hepatitis in winter and summer. In
      winter, normalization of biochemical indices was slow while efficacy of
      physiotherapy with sapropel combined with magnetic field was high. In summer,
      normalization of biochemical indices was more active but the above combination
      was less effective.

PMID- 15717534
TI  - [Results of early rehabilitation after various methods of cholecystectomy at Ust'
      Kachka resort].
AB  - Early rehabilitation after open cholecystectomy or cholecystectomy from a mini
      approach was performed in 101 patients with cholelithiasis treated surgically at
      Ust-Kachka health resort. Changes in clinico-laboratory indices reflecting the
      condition of hepatopancreatobiliary system and central hemodynamics before and
      after rehabilitation were studied depending on the variant of cholecystectomy.
      Advantages of early rehabilitation of patients after different variants of
      cholecystectomy at Ust-Kachka health resort in normalization of general condition
      of the patients and in prevention of functional disorders progression early after
      operation are demonstrated.

PMID- 15717535
TI  - [Hormonal and metabolic effects of drinking mineral water and phytoaeronisation
      in experimental prostatitis].
AB  - Prostatitis modelled in 53 Wistar male rats (300-350 body mass) 7 days after its
      induction was treated with mineral water "Essentuki N 17" (MW) which was taken in
      a dose 1.5-2 ml per 100 g body mass for 23-24 days. In addition, some animals
      received phytoaeroionisation (PAI) with solution of essential oils of mint, sage
      and lavender. Prostatitis is associated with disorders in prostatic tissue,
      levels of sex hormones (testosterone, prolactin, FSH, LH), a rise in total
      cholesterol, glucose. Watering of animals with MW and PAI raised blood insulin,
      hydrocortisone and testosterone, normalized blood glucose and cholesterol. There
      was a correlation between blood levels of hydrocortisone and testosterone.

PMID- 15717536
TI  - [Influence of microwave magnetoresonance therapy on various parameters of local
      immune defence in the respiratory tract in ailing children].
AB  - Microwave magnetoresonance therapy (MMT) was performed in 50 preschool children
      who had frequent respiratory infections. The assessment of local antiinfectious
      defense factors registered a significant decrease in the total number of
      circulating immune complexes (CIC) with disappearance of small CIC; enhancement
      of total complementory activity and C2, C4-fragments of the complement indicating
      activation of mucosa of the mucosa-associated lymphoid tissue inductive zone
      providing specific antibacterial defense of the upper respiratory tract.

PMID- 15717537
TI  - [Low-frequency magnetotherapy to raise performance and correction of immune
      status in athletes].

PMID- 15717538
TI  - [Physiotherapy in combined treatment of patients with genital tuberculosis].
AB  - One hundred and thirty six women with genital tuberculosis received combined
      antibacterial treatment (ABT) with adjuvant physiotherapy. The patients were
      divided into three groups: patients of group 1 had active genital tuberculosis
      treated with ABT plus electrophoresis of 3% sodium thiosulphate, group 2 had
      chronic tuberculous process treated with ABT plus ultrasound hydrocortisone
      therapy, group 3 received ABT alone. The findings demonstrate that noticeable
      improvement and reduction of treatment duration were observed in groups 1 and 2.

PMID- 15717539
TI  - [Efficacy of intensive manual therapy in severe multiple trauma].
AB  - How intensive rehabilitation influences external respiration function, central
      and peripheral hemodynamics in the injured with a severe multitrauma was
      investigated in 71 injured. Intensive rehabilitation in combined treatment is
      shown to improve external respiration function, central hemodynamics, tissue
      blood flow, sleep, appetite, healing of bedsores, to enhance cough reflex.

PMID- 15717540
TI  - [Effects of drinking sulfate mineral water in combination with laser and
      magnetolaser radiation on spermatogenesis in irradiated rats].

PMID- 15717541
TI  - [Treatment of cardiological patients with radon baths].

PMID- 15717542
TI  - [Intracavitary electrostimulation in the treatment of patients with chronic
      pancreatitis].

PMID- 15717543
TI  - [Magnetolaser therapy in chronic prostatitis].

PMID- 15717544
TI  - [Efficacy of biofeedback for correction of disturbed psychological adaptation in
      patients with chronic somatic diseases].

PMID- 15717545
TI  - [Psychological characteristics and pain perception in patients with chronic
      salpingoophoritis].

PMID- 15717546
TI  - [Therapeutic exercise in patients with thermoinhalation trauma at the early
      hospital stage].

PMID- 15717548
TI  - [Physiotherapy in the treatment of neuromuscular diseases].

PMID- 15717547
TI  - [Structure of the Center for Sanatorium Rehabilitation of patients with
      occupational diseases and individuals suffered work-related accidents].

PMID- 15717549
TI  - Foveal contour interaction: detection and discrimination.
AB  - Contour interaction, the detrimental effect of flanking features on the
      discrimination of optotypes, has been studied mainly close to the visual acuity
      limit. We were interested to know how these results compare with those for the
      detection of targets. According to the simplest model of contour interaction,
      comparable detection effects would be expected. The case for low-level masking
      would be further strengthened if the form and nature of the dependence on flank
      separation and flank polarity followed that typically found in studies of lateral
      spatial masking [Vision Res. 33, 993 (1993)]. Landolt Cs subtending a visual
      angle of 0.25 degrees, 0.5 degrees, and 1.0 degrees were presented and contrast
      thresholds for detecting the presence of the Landolt C and discriminating its
      orientation were measured in five normal subjects as a function of flank
      separation and flank polarity. The results obtained for the relationship between
      detection and discrimination depend on the size of the target used. For small
      letters, discrimination but not detection was significantly affected by flanking
      bars. For large letters, detection and discrimination were affected to the same
      extent. However, in this case the effectiveness of opposite-polarity flanks and
      the finding that facilitation occurred at close, not far, flank separations
      suggests that the simplest explanation in terms of masking may not be applicable.

PMID- 15717550
TI  - Image-based face recognition under illumination and pose variations.
AB  - We present an image-based method for face recognition across different
      illuminations and poses, where the term image-based means that no explicit prior
      three-dimensional models are needed. As face recognition under illumination and
      pose variations involves three factors, namely, identity, illumination, and pose,
      generalizations in all these three factors are desired. We present a recognition
      approach that is able to generalize in the identity and illumination dimensions
      and handle a given set of poses. Specifically, the proposed approach derives an
      identity signature that is illumination- and pose-invariant, where the identity
      is tackled by means of subspace encoding, the illumination is characterized with
      a Lambertian reflectance model, and the given set of poses is treated as a whole.
      Experimental results using the Pose, Illumination, and Expression (PIE) database
      demonstrate the effectiveness of the proposed approach.

PMID- 15717551
TI  - Spherical-wave intensity diffraction tomography.
AB  - An extension of the recently developed method of intensity diffraction tomography
      is derived that assumes that the probing field is a spherical wave produced by a
      point source sufficiently far from the scatterer. A discussion of the method and
      numerical reconstructions of a simulated three-dimensional scattering object are
      presented.

PMID- 15717552
TI  - Generalized algebraic scene-based nonuniformity correction algorithm.
AB  - A generalization of a recently developed algebraic scene-based nonuniformity
      correction algorithm for focal plane array (FPA) sensors is presented. The new
      technique uses pairs of image frames exhibiting arbitrary one- or two-dimensional
      translational motion to compute compensator quantities that are then used to
      remove nonuniformity in the bias of the FPA response. Unlike its predecessor, the
      generalization does not require the use of either a blackbody calibration target
      or a shutter. The algorithm has a low computational overhead, lending itself to
      real-time hardware implementation. The high-quality correction ability of this
      technique is demonstrated through application to real IR data from both cooled
      and uncooled infrared FPAs. A theoretical and experimental error analysis is
      performed to study the accuracy of the bias compensator estimates in the presence
      of two main sources of error.

PMID- 15717554
TI  - Low-coherence light-scattering calculations for polydisperse size distributions.
AB  - The calculation of angular light-scattering distributions is considered for low
      coherence light incident on a polydisperse particle size distribution of
      scatterers. As low-coherence light is now commonly used in interferometry schemes
      when applied to biomedical imaging, the difference between detecting scattered
      intensity and interferometrically detecting the scattered field is examined. An
      expression is derived that allows the presence of multiple wavelengths lambda and
      particle sizes d to be described by a single distribution in the size parameter x
      = pi d/lambda, which simplifies numerical calculations. The applicability of this
      expression is examined numerically.

PMID- 15717553
TI  - Reconstruction of spatially inhomogeneous dielectric tensors through optical
      tomography.
AB  - A method to reconstruct weakly anisotropic inhomogeneous dielectric tensors
      inside a transparent medium is proposed. The mathematical theory of integral
      geometry is cast into a workable framework that allows the full determination of
      dielectric tensor fields by scalar Radon inversions of the polarization
      transformation data obtained from six planar tomographic scanning cycles.
      Furthermore, a careful derivation of the usual equations of integrated
      photoelasticity in terms of heuristic length scales of the material inhomogeneity
      and anisotropy is provided, resulting in a self-contained account about the
      reconstruction of arbitrary three-dimensional, weakly anisotropic dielectric
      tensor fields.

PMID- 15717555
TI  - Variables affecting polarization-sensitive optical coherence tomography imaging
      examined through the modeling of birefringent phantoms.
AB  - Characteristics of tissue birefringence provide valuable diagnostic information
      when optical coherence tomography (OCT) imaging is performed. We mathematically
      model single-detector polarization-sensitive (PS) OCT (PS-OCT) for imaging an
      alternating layered phantom with birefringence. The theoretical analysis and the
      simulated data all reveal complexities associated with PS-OCT imaging. Various
      tissue parameters affect the retrieved PS-OCT signal and hence the image
      features. A better understanding of the mechanisms that control PS-OCT imaging
      would be useful for interpretation of tissue images and ultimately useful to
      provide more diagnostic information.

PMID- 15717556
TI  - Three-dimensional superresolution by three-zone complex pupil filters.
AB  - Complex pupil filters are introduced to improve the three-dimensional resolving
      power of an optical imaging system. Through the design of the essential
      parameters of such filters, the transmittance and radius of the first zone, three
      dimensional superresolution is realized. The Strehl ratio and the transverse and
      axial gains of such filters are analyzed in detail. A series of simulation
      examples of such filters are also presented that prove that three-dimensional
      superresolution can be realized. The advantage of such filters is that it is easy
      to realize three-dimensional superresolution, and the disadvantage is that the
      sidelobes of the axial intensity distribution are too high. But this can be
      overcome by the application of a confocal system.

PMID- 15717557
TI  - Analysis of diffraction gratings by using an edge element method.
AB  - Typically the grating problem is formulated for TE and TM polarizations by using,
      respectively, the electric and magnetic fields aligned with the grating wall and
      perpendicular to the plane of incidence, and this leads to a one-field-component
      problem. For some grating profiles such as metallic gratings with a triangular
      profile, the prediction of TM polarization by using a standard finite-element
      method experiences a slower convergence rate, and this reduces the accuracy of
      the computed results and also introduces a numerical polarization effect. This
      discrepancy cannot be seen as a simple numerical issue, since it has been
      observed for different types of numerical methods based on the classical
      formulation. Hence an alternative formulation is proposed, where the grating
      problem is modeled by taking the electric field as unknown for TM polarization.
      The application of this idea to both TE and TM polarizations leads to a two-field
      component problem. The purpose of the paper is to propose an edge finite-element
      method to solve this wave problem. A comparison of the results of the proposed
      formulation and the classical formulation shows improvement and robustness in the
      new approach.

PMID- 15717558
TI  - Helmholtz-Gauss waves.
AB  - A detailed study of the propagation of an arbitrary nondiffracting beam whose
      disturbance in the plane z = 0 is modulated by a Gaussian envelope is presented.
      We call such a field a Helmholtz-Gauss (HzG) beam. A simple closed-form
      expression for the paraxial propagation of the HzG beams is written as the
      product of three factors: a complex amplitude depending on the z coordinate only,
      a Gaussian beam, and a complex scaled version of the transverse shape of the
      nondiffracting beam. The general expression for the angular spectrum of the HzG
      beams is also derived. We introduce for the first time closed-form expressions
      for the Mathieu-Gauss beams in elliptic coordinates and for the parabolic Gauss
      beams in parabolic coordinates. The properties of the considered beams are
      studied both analytically and numerically.

PMID- 15717559
TI  - Polarization-insensitive high-dispersion total internal reflection diffraction
      gratings.
AB  - We report the first experimental realization of total internal reflection (TIR)
      diffraction gratings. Performance of less than 0.7-dB insertion loss (IL) for
      both TE and TM polarizations and 0.5-dB polarization-dependent loss (PDL) are
      predicted over a 50-nm spectral bandwidth with simultaneous fabrication
      tolerances on the depth and the duty cycle of binary gratings of +/-5% and +/
      14%, respectively. Nineteen gratings were fabricated that met these
      specifications, yielding IL and PDL values less than 0.6 and 0.2 dB,
      respectively, across the entire 50-nm bandwidth. Measurements made under the
      Littrow configuration resulted in high efficiency and low PDL across a 100-nm
      bandwidth, with up to 100% diffraction efficiency within the experimental
      measurement error.

PMID- 15717560
TI  - Ince-Gaussian beams in a quadratic-index medium.
AB  - The propagation of Ince-Gaussian beams in media where the refractive index varies
      quadratically with the distance from the optical axis is studied. Explicit
      expressions for the complex beam parameter and the longitudinal phase shift are
      derived and discussed. Ince-Gaussian eigenmodes with constant width can be
      obtained by satisfying a relation between the beam width and the quadratic-medium
      coefficient. The derivation has included the possibility of propagation of Ince
      Gaussian beams in complex lenslike media having quadratic transverse variations
      of the index of refraction and the gain or loss.

PMID- 15717561
TI  - Linear systems modeling of adaptive optics in the spatial-frequency domain.
AB  - Spatial-frequency domain techniques have traditionally been applied to obtain
      estimates for the independent effects of a variety of individual error sources in
      adaptive optics (AO). Overall system performance is sometimes estimated by
      introducing the approximation that these individual error terms are statistically
      independent, so that their magnitudes may be summed in quadrature. More accurate
      evaluation methods that account for the correlations between the individual error
      sources have required Monte Carlo simulations or large matrix calculations that
      can take much longer to compute, particularly as the order of the AO system
      increases beyond a few hundred degrees of freedom. We describe an approach to
      evaluating AO system performance in the spatial-frequency domain that is
      relatively computationally efficient but still accounts for many of the
      interactions between the fundamental error sources in AO. We exploit the fact
      that (in the limits of an infinite aperture and geometrical optics) all the basic
      wave-front propagation, sensing, and correction processes that describe the
      behavior of an AO system are spatial-filtering operations in the Fourier domain.
      Essentially all classical wave-front control algorithms and evaluation formulas
      are expressed in terms of these filters and may therefore be evaluated one
      spatial-frequency component at a time. Performance estimates for very-high-order
      AO systems may be obtained in 1 to 2 orders of magnitude less time than needed
      when detailed simulations or analytical models in the spatial domain are used,
      with a relative discrepancy of 5% to 10% for typical sample problems.

PMID- 15717562
TI  - Designing a mirror to realize a given projection.
AB  - I present a design technique for realizing given projections as catadioptric
      sensors. In general, these problems do not have solutions, but approximate
      solutions may often be found that are visually acceptable. The method described
      reduces the problem to solving a linear system. A given transformation from the
      image plane to an object surface is shown to determine a vector field that is
      normal to the surface in the case where the vector field is a gradient. For the
      case when the vector field is not a gradient, several functionals are presented
      that may be minimized to give approximate solutions. As an application several
      new designs are described, including a mirror that directly gives a full 360-deg
      cylindrical projection without the need for any digital processing.

PMID- 15717563
TI  - High-efficiency reflective diffraction gratings in fused silica as
      (de)multiplexers at 1.55microm for dense wavelength division multiplexing
      application.
AB  - We describe high-efficiency, high-dispersion reflection gratings fabricated in
      bulk fused silica illuminated by incident lights in the C + L bands as
      (de)multiplexers for dense wavelength division multiplexing (DWDM) application.
      Based on the phenomenon of total internal reflection, gratings with optimized
      profile parameters exhibit diffraction efficiencies of more than 90% under TM-
      and TE-polarized incident lights for 101-nm spectral bandwidths (1520-1620 nm)
      and can reach an efficiency of greater than 97% for both polarizations at a
      wavelength of 1550 nm. Without loss of metal absorption, without coating of
      dielectric film layers, and independent of tooth shape, this new kind of grating
      should be of great interest for DWDM application.

PMID- 15717564
TI  - Detection of subwavelength slit-width variation with measurements in the far
      field by use of an embedded-aperture interferometer configuration.
AB  - The dynamic signature of the subwavelength variation of a rectangular aperture
      has recently been shown to be determinable from far-field irradiance with a
      precision better than 1 nm [Opt. Lett. 29, 1045 (2004)]. We have proposed, and
      have theoretically shown, that detection sensitivity can be greatly enhanced with
      an embedded-aperture Mach-Zehnder interferometer configuration, after parameter
      optimization. The sensitivity, in terms of derivative intensity of observed
      subwavelength variations, could be enhanced approximately 2.7 times, compared
      with the directly detected method. Another method of detection of subwavelength
      variation from pattern measurement of far-field diffraction has also been
      proposed. The associated shifting of the dark line of the diffraction pattern had
      a good linear correlation to subwavelength variation, which was magnified
      approximately 150 times, and gave good contrast for measurement.

PMID- 15717565
TI  - Photon-sieve lithography.
AB  - We present the first lithography results that use high-numerical-aperture photon
      sieves as focusing elements in a scanning-optical-beam-lithography system [J.
      Vac. Sci. Technol. B 21, 2810 (2003)]. Photon sieves are novel optical elements
      that offer the advantages of higher resolution and improved image contrast
      compared with traditional diffractive optics such as zone plates [Nature 414, 184
      (2001)]. We fabricated the highest-numerical-aperture photon sieves reported to
      date and experimentally verified their focusing characteristics. We propose two
      new designs of the photon sieve that have the potential to significantly increase
      focusing efficiency.

PMID- 15717566
TI  - Finite-difference time-domain simulation of a liquid-crystal optical phased
      array.
AB  - Accurate modeling of a high-resolution, liquid-crystal-based, optical phased
      array (OPA) is demonstrated. The modeling method is extendable to cases where the
      array element size is close to the wavelength of light. This is accomplished
      through calculating an equilibrium liquid-crystal (LC) director field that takes
      into account the fringing electric fields in LC OPAs with small array elements
      and by calculating the light transmission with a finite-difference time-domain
      method that has been extended for use in birefringent materials. The diffraction
      efficiency for a test device is calculated and compared with the simulation.

PMID- 15717567
TI  - Numerical study on an asymmetric guided-mode resonant grating with a Kerr medium
      for optical switching.
AB  - Optical switching effects of a guided-mode resonant grating (GMRG) with a Kerr
      medium have been simulated with the nonlinear finite differential time domain
      (FDTD) method. An asymmetric waveguide grating with a large second spatial
      harmonic component has been proposed for the optical switch. Resonant reflection
      occurs at both of the band-edge wavelengths. These wavelengths are used for the
      pump light and the probe light. The enhanced electric field of the pump light
      changes the resonant wavelength for the probe light as a result of the Kerr
      effect. We designed the GMRG with resonant wavelengths of 1489.6 and 1630 nm,
      which were used for the pump light and the probe light, respectively. When the
      grating material has a third-order susceptibility chi(3) of 8.5 x 10(-10) esu,
      the transmittance of the probe light changes from 0 to 80% by increasing the
      intensity of the pump light from 0 to 60 kW/mm2.

PMID- 15717568
TI  - Beam dynamics of two modes propagating along the optic axis in a uniaxial
      crystal.
AB  - The Gaussian beam propagation in the direction of the optic axis of a uniaxial
      crystal is treated by the complex-source-point technique. At the input plane the
      electric field is linearly polarized. A particular superposition of the ordinary
      mode and the extraordinary-mode beams is generated. The electrodynamics of the
      composite beam has features that are different from those of the two constituent
      beams. As a result of the anisotropy, on propagation, the cross-polarized
      component of the electric field is generated except along the beam axis; the
      cross section of the beam, which is circular at the input plane, becomes
      elliptical; and the mean squared width of the beam departs from the usual
      quadratic dependence on the distance from the waist in the direction of
      propagation.

PMID- 15717569
TI  - Three-dimensional metallo-dielectric photonic crystals with cubic symmetry as
      stacks of two-dimensional screens.
AB  - Metallo-dielectric photonic crystals with cubic symmetries have been studied here
      both experimentally and theoretically in the millimeter wavelength region (15-60
      mm). In a direct analogy to linear systems, we considered the three-dimensional
      lattices as a stack of two-dimensional resonating screens. The overall three
      dimensional structure was introduced in the calculation through a structural
      phase. Such an approach proved useful in understanding the related mode
      propagation and guided us in a study of the transition between cubic and centered
      body cubic symmetries.

PMID- 15717570
TI  - Method for measuring off-diagonal Kerr coefficients by using polarized light
      transmission.
AB  - We report a method for measuring the off-diagonal coefficients of the quadratic
      electro-optic (Kerr) tensor by using polarized light transmission. The method
      relies on designing an experimental configuration in which the linear electro
      optic (Pockels) effect does not contribute to the data. Our method can be used to
      obtain off-diagonal Kerr coefficients for all but two of the 20 crystal point
      groups for which the Pockels effect and the Kerr effect coexist. Our theoretical
      model includes effects from transmission, multiple reflections, and
      electrostriction but neglects absorption in the crystal. To verify the method, we
      used it to measure the R12 and R13 Kerr coefficients for a (100)-type single
      crystal of ferroelectric barium titanate (BaTiO3) at room temperature (23.5
      degrees). To our knowledge, this is the first time this method has been used and
      the first time these coefficients have been measured for the unclamped crystal in
      the tetragonal state. The mean values obtained with this method are R12 = -3.5+/
      0.3 x 10(-17) m2/V2 and R13 = -8.0+/-0.7 x 10(-17) m2/V2.

PMID- 15717571
TI  - Optimal annular computer-generated holograms for the generation of optical
      vortices.
AB  - We analyze a method for efficiently generating optical vortices by use of annular
      computer-generated holograms and a spatial light modulator. We found that there
      exists an optimal annular width by which the reconstructed vortex ring in the
      focal plane has the steepest gradient and the worthless subbright rings can be
      largely suppressed. We fitted a general formula for determining the value of this
      optimal annular width and propose a method for designing a multiring structure of
      optical vortices and specialized interferometric vortex patterns. Finally, we
      discuss the situation of a Gaussian beam as illuminated light and find that there
      exists an optimal beam waist that results in the best energy efficiency.

PMID- 15717572
TI  - Nondialysis (home) medication utilization and cost in diabetic and nondiabetic
      hemodialysis patients.
AB  - Hemodialysis patients take an average 12 medications (10 at home, 2 in clinic).
      Cost associated with clinic medications is estimated at 8,429 dollars per patient
      year at risk, but the medication cost associated with home medications is
      unknown. Our objective was to determine an estimate of the cost of home
      medications in the hemodialysis population. Point-prevalent patient medication
      use data (Jan. 1, 2003) from the Dialysis Clinic Inc. (DCI) national database was
      used for the study. All patients were classified as patients with diabetes (DM)
      or patients without diabetes (nonDM), and medication orders were divided into
      home and in-clinic medications. Home medications were classified as brand (B),
      generic (G), or brand that could be generic (BG). All home medications were
      further subcategorized into 12 therapeutic classes. National average medication
      cost for brand (76.29 dollars) and generic (22.79 dollars) medications were
      applied to the orders. The medication profiles of 10,230 HD patients were
      surveyed. Overall, patients were on a mean of 10.1 +/- 4.6 home medications.
      Currently, 53.4% of the health care dollar is spent on cardiac, gastrointestinal,
      and phosphate binding medications. DM patients spent significantly more on
      cardiac, gastrointestinal, and endocrine/hormonal agents (all p < 0.001) whereas
      nonDM patients spent more on anti-infective agents, analgesics, and phosphate
      binders (all p < 0.05). Medications for HD patients cost 16,000 dollars per
      patient per year. Health care providers should be aware of the medication cost
      burden in HD patients. Efforts to decrease this burden, whether through
      pharmaceutical care, generic prescribing, or sampling programs, should be
      considered.

PMID- 15717573
TI  - Re-engineering the ESRD Program amid Medicare reform.

PMID- 15717574
TI  - Lessons learned in an urban CKD clinic.

PMID- 15717575
TI  - The process of implementing a CKD clinic.
AB  - Chronic kidney disease patients are complex, and usually have multiple comorbid
      conditions. It is evident that a CKD clinic can improve clinical outcomes and
      patient satisfaction. It is widely recognized that education, patient
      empowerment, early recognition of the disease, and appropriate and timely
      interventions in patients with CKD can positively influence the clinical outcomes
      in this population. So why is it so difficult to deliver CKD care?

PMID- 15717576
TI  - Defining the impact of high patient/staff ratios on dialysis social workers.
AB  - In the beginning of 2003, the renal provider in Connecticut with the largest
      market share systematically reduced the hours of social workers and dietitians
      throughout its units. This change was part of a larger strategy of "leveraging
      and maximizing... organizational and management structure to improve patient,
      employee, and business care, including increased management emphasis on improving
      return on invested capital." For social workers in this company, the target ratio
      appeared to be 160 patients per 1 full-time equivalent. Soon after this increase
      in case ratio, the Connecticut Council of Nephrology Social Workers (CT CNSW)
      became concerned about the reduced level of social work services available to
      patients.

PMID- 15717577
TI  - Doctors' Day: IMA's concern for rural health and NHP for BPL people.

PMID- 15717578
TI  - Parasitosis: a study among Nepali children in the district of Darjeeling.
AB  - A cross-sectional study carried out among 370 school-going children of the Nepali
      community, aged 5-10 years, in the Siliguri subdivision of Darjeeling district
      revealed the prevalence of parasitic infestation to be 51.4 per cent of which
      28.2% and 23.2% had single and multiple parasitism respectively. In the group of
      single parasitism, A. lumbricoides was the commonest infestation (31.73%) and in
      multiple parasitisms, A. lumbricoides and T. Trichiura combination was found to
      be the most prevalent (36.05%). A significant statistical association was
      observed in the decrease of worm infestation rate among children with the
      increasing educational status of their mothers. The study also revealed that
      19.73% and 18.91% of the mothers had no knowledge about mode of transmission and
      prevention of worm infestation respectively.

PMID- 15717579
TI  - Clinical profile and outcome of acute renal failure in South Indian children.
AB  - This was a retrospective study to assess the clinical profile of children
      admitted with acute renal failure and to identify factors associated with poor
      outcome. Fifty-four children (age one month to 12 years) with acute renal failure
      were studied. Males outnumbered females (38/54; 70%). The leading precipitating
      causes for renal failure were acute gastro-enteritis (85%), underlying renal
      pathology (43%), proven sepsis (22%) and suspected sepsis (22%). The main
      presenting complaints were diarrhoea (86%),oliguria (72%), rapid respiration
      (37%), oedema (37%), vomiting (19%) and seizures (13%). All patients underwent
      standard investigations and treatment. Forty-eight per cent of patients required
      peritoneal dialysis and 15% required ventilation. The overall mortality was 52%.
      Underlying renal pathology and sepsis both contributed to the high morbidity and
      mortality. Mortality due to sepsis was 83%; it was 65% in dialysed patients and
      100% in those requiring ventilatory support. Biochemical profile of the above
      patients showed that hyperkalaemia was significantly associated with high
      mortality (83%) as against 75% in those with hypokalaemia and 33% with normal
      levels (p<0.001). Patients with hyponatraemia and hypernatraemia similarly had an
      adverse outcome. Acidosis, seen in 20 patients, had a mortality of 45%. The
      outcome was poorer in those with high creatinine levels (63%).

PMID- 15717580
TI  - A study of peak expiratory flow rates among tribal children of Mysore District.
AB  - In the context of a growing need for a comprehensive body of normal value of peak
      expiratory flow rate (PEFR) among tribal children, the present study was
      undertaken. Two hundred forty-two children belonging to two scheduled tribes
      'Soliga' and 'Jenukurubas' were studied, their PEFR was recorded and correlated
      with anthropometric data. There was a significant positive correlation between
      PEFR and age, height, weight, body surface area, arm span and chest expansion in
      the study group. This was compared with other Indian and Western studies and a
      nomogram to predict PEFR from height was constructed.

PMID- 15717581
TI  - Two-port and single port laparoscopic appendicectomy.
AB  - Minimally invasive surgery for appendicectomy generally involves use of 3 or 4
      ports. But if the procedure can be safely performed using two or even a single
      port, it would be beneficial to the patient, since it is less invasive than
      standard procedure. The present article describes an experience of laparoscopic
      appendicectomy using only two ports and occasionally a single port and highlights
      its efficacy and safety.

PMID- 15717582
TI  - Geriatric problems in otolaryngology.
AB  - Overall data in the feld of 'gerontology' are scarce in India. Some major
      geriatric problems in otolaryngology like presbyacusis, disequilibrium, vertigo,
      tinnitus, nasal and pharyngeal changes, voice change, dysphagia, arthritis,
      snoring, falls, have been briefly addressed to in the present article.

PMID- 15717583
TI  - Quality control and automation in cervical cytology.
AB  - Pap smear is a clinical screening test and does not have 100% sensitivity and
      specificity. Sensitivity of pap smear can be improved with proper collection
      techniques and education of all concerned. Implementation and maintenance of
      quality control measures help to detect, reduce and correct deficiencies in pap
      smear analysis. Advent of automated devices has provided an opportunity to
      further improve the sensitivity of pap smear. Automation in cytology, seemed
      wildly speculative a decade ago, is becoming a reality now. Areas of automation
      include: Data storage and retrieval by computers, automatic staining and
      coverslipping machines, sample preparation methods, screening process control
      devices and imaging systems for searching and interpretation of abnormal cells.

PMID- 15717584
TI  - Prolymphocytic leukaemia--report of three cases.
AB  - Prolymphocytic leukaemia is a rare subtype of chronic lymphocytic leukaemia.
      Three such cases are reported here along with clinical details. All these cases
      were seen in males above 5th decade of life. These patients showed moderate to
      massive splenomegaly, inconspicuous lymphadenopathy in two cases and one with
      minimal lymphadenopathy. Peripheral smear showed high leucocyte count with more
      than 55% of prolymphocytes. Bone marrow aspiration showed diffuse involvement;
      and in one with minimal lymphadenopathy, lymph node aspiration showed
      prolymphocytes. All the three patients died within a year after diagnosis.

PMID- 15717585
TI  - Endometrioid carcinoma of uterus and ovary.
AB  - A thirty-two-year-old married woman presented with pain abdomen and
      polymenorrhoea. Her uterus was bulky and one of the fornices was full. USG of
      abdomen revealed unilateral ovarian tumour associated with a mass in the uterus.
      Histopathological report revealed synchronous endometrioid carcinoma of the
      uterus and the ovary with morphological evidences in favour of independent
      primary carcinomas. With these perspectives the present case is reported where
      endometrioid carcinomas of uterus and ovary are two separate primary tumours.

PMID- 15717586
TI  - Adult polycystic liver disease presenting as portal hypertension.
AB  - Autosomal dominant polycystic liver disease is a systemic hereditary disorder
      associated with cyst formation in the ductal organs such as the kidney and liver.
      Multiple massive cysts are typically found in multiparous women. Portal
      hypertension as a presenting manifestation is very rare but may be caused by
      associated hepatic fibrosis or massive hepatic replacement of liver by the cysts.
      Two cases of adult polycystic liver disease, one in uniparous female and another
      in a 45-year-old male, both presenting with portal hypertension and without any
      demonstrable fibrosis in the liver, are reported here.

PMID- 15717587
TI  - Pseudoaneurysm in injecting drug abusers.

PMID- 15717588
TI  - The role of consultant practitioners--consultant nurses and midwives.

PMID- 15717589
TI  - Fulfilling their potential?

PMID- 15717590
TI  - E-nursing and e-patients.

PMID- 15717591
TI  - Building leadership from ward to board.

PMID- 15717592
TI  - The whole truth?

PMID- 15717593
TI  - A day in the life.

PMID- 15717594
TI  - Global thinking. Interview by Debbie Andalo.

PMID- 15717595
TI  - Growing our own: a model for encouraging and nurturing aspiring leaders.
AB  - DEVELOPMENTS IN western society have led us to question traditional leadership
      structures. This is particularly so in the context of care as people's health and
      social care needs change, technology advances and public expectations rise
      (Department of Health 1999). Bennis (2000), and Kouzes and Posner (2003),
      identify a style of leadership known as 'transformational leadership', which
      describes the ability of leaders to influence others by transforming their
      behaviour without necessarily being in positions of authority. Such leaders can
      inspire others to follow them by displaying characteristic leadership behaviours.
      These leadership behaviours are described by Kotter (1990) and are laid out in
      Table 1.

PMID- 15717596
TI  - Settings for death and dying.

PMID- 15717597
TI  - Detection of the env MMTV-homologous sequences in mammary carcinoma patient
      intestine lymphoid tissue.

PMID- 15717598
TI  - Nuclear magnetic resonance flow electrodialysis: implications for experimental
      biology and medicine.

PMID- 15717599
TI  - Female nutrition quality during lactation changes the functions of enzyme systems
      in digestive and nondigestive organs of the second-generation progeny.

PMID- 15717600
TI  - Betulonic acid and derivatives, a new group of agents reducing side effects of
      cytostatics.

PMID- 15717601
TI  - Changes in quantal content of the evoked postsynaptic currents in synapses with
      constant release probability.

PMID- 15717602
TI  - The immunomodulating effects of hydrocortisone and adrenaline against the
      background of blockage of opiate receptors.

PMID- 15717603
TI  - Modeling the effect of amiloride in studies of conductance of nanometer channels
      of synthetic track membranes.

PMID- 15717604
TI  - The shift of the reversal potential of glutamate-activated chloride current in
      molluscan neurons caused by 8-Br-cAMP.

PMID- 15717605
TI  - Distribution of calcium-binding proteins in the central and peripheral regions of
      the turtle mesencephalic center torus semicircularis.

PMID- 15717606
TI  - Unilateral injury of the sensorimotor cortex of the dominant or subdominant
      hemisphere in female Wistar rats determines the neurological and immune statuses
      of their offspring.

PMID- 15717607
TI  - Effect of tetraalkylammonium derivatives of 6-methyluracil on the endplate
      potentials of muscles of different functional types.

PMID- 15717609
TI  - Trapping blockage of muscle nicotinic cholinoreceptors by mecamilamine.

PMID- 15717608
TI  - Antibodies against gangliosides GM1 of patients with multiple sclerosis alter the
      response of neurons to synaptic activation.

PMID- 15717610
TI  - Assessment of the rate of accumulation of the transuranium element americium-241
      by the aquatic plant Elodea canadensis.

PMID- 15717611
TI  - Arboricular (tree-dwelling) oribatid mites as bioindicators of environment
      quality.

PMID- 15717612
TI  - Optimization of fixation and fermentation regimes for some species of medicinal
      plants with the alkaloid type of metabolism.

PMID- 15717613
TI  - Adaptive significance of the sexual size dimorphism in the fish ectoparasite
      Argulus coregoni (Crustacea: Branchiura).

PMID- 15717614
TI  - Strategy of chemical design of phytoregulators and stress protectors with the
      given properties.

PMID- 15717615
TI  - The role of the diffusion permeability of soils in the regulation of methane
      emission on gas-bearing areas.

PMID- 15717616
TI  - Time course of the activity of extracellular peroxidases of potato suspension
      cell cultures in ring rod pathogenesis.

PMID- 15717617
TI  - Microbial production of methane in the aerobic water layer of the Black Sea.

PMID- 15717618
TI  - Environment toxicity as a new universal characteristic of the pollution of
      objects tested.

PMID- 15717619
TI  - Diallyl sulfide depletes the inositol trisphosphate-sensitive intracellular Ca2+
      stores and activates SOC-channels in HL-60 human cells.

PMID- 15717620
TI  - Specificity of the proteasome population secreted from cells into the culture
      medium.

PMID- 15717621
TI  - Sister aneuploid cells enter cycloheximide-induced apoptosis asynchronously.

PMID- 15717622
TI  - Avoid pitfalls with corrective action plans: quality experts share strategies.

PMID- 15717623
TI  - Is your falls prevention program getting results?

PMID- 15717624
TI  - Are you ready for JCAHO's medication standards?

PMID- 15717625
TI  - JCAHO alert gives new recommendations for PCA.

PMID- 15717626
TI  - Taking measure with focus groups.

PMID- 15717627
TI  - Glomerular disease in patients with malignant disease: four cases and review of
      literature.
AB  - Renal involvement may occur in cases with malignant disorders. Glomerular injury
      may be the first sign of these diseases and may predict the overall survival. In
      some cases, glomerular injury may be associated with tumor antigens, and in some
      others, viruses cause renal injury together with underlying malignant disease.
      Here we report four cases with malignant diseases and accompanying glomerular
      injury and review the literature.

PMID- 15717628
TI  - Influence of ischemia on heart-rate variability in chronic hemodialysis patients.
AB  - BACKGROUND: Sudden cardiac death occurring in patients with end-stage renal
      disease (ESRD) may be related to poor autonomic function with a significant
      decreased heart-rate variability (HRV). In addition, coronary artery disease has
      a high prevalence in this population and accounts for 50% of deaths. In the
      present study, relationships between HRV and myocardial ischemic abnormalities
      revealed by myocardial scintigraphy (MS) were evaluated in 32 chronic
      hemodialysis patients. METHODS: We prospectively studied 32 chronic hemodialysis
      patients. Each underwent MS and 24 h electrocardiography at baseline for analysis
      of time and frequency domain the day of dialysis. Three periods were analyzed:
      during dialysis session, the morning after (nondialytic period), and in a 24 h
      period. Patients were included in group 1 (seven women, 11 men; mean age: 62+/-19
      years) when MS revealed no ischemia, whereas patients were included in group 2
      (seven women, seven men; mean age: 63.1+/-20 years) when MS revealed ischemic
      lesions. RESULTS: A student+/-test revealed that during the nondialytic period,
      two important markers of HRV, percentage of delta RR>50 ms (pNN50) (4.5+/-4.04 in
      group 1 versus 1.7+/-1.4 in group 2), and root mean square of delta RR (rMSSD)
      (27.7+/-13.4 versus 19.7+/-6.8) were significantly reduced in group 2 compared
      with values in group 1. No significant difference appears between the two groups
      for standard deviation of normal to normal intervals (SDNN), mean heart rate, and
      spectral analysis. CONCLUSION: Patients with ESRD and myocardial ischemia
      revealed by MS have reduced parasympathetic activity during the nondialytic
      period. Correlations between parameters of HRV and ischemic lesions revealed by
      MS have been shown for the first time.

PMID- 15717629
TI  - Significance of proto-oncogene Bcl-X(S/L) expression in Wilms tumor.
AB  - The rate of apoptosis varies in malignant tumors, and it can be involved in
      diminishing tumor size. Different protein-regulators of apoptosis, such as Bcl-2,
      BclX, and Bax have an influence on the rate of apoptosis in various tumors. In
      human renal diseases, such as the experimental model of acute renal failure, and
      many tumors, including Wilms' tumor, the expression of antiapoptotic members of
      Bcl-2 family is increased, while the expression of proapoptotic members is low.
      AIM: The aim of our study was to investigate Bcl-X(S/L) protein expression in
      Wilms' tumor, to compare it with the expression in normal renal tissue, as well
      as to see if there is a correlation between Bcl-X(S/L) expression in Wilms' tumor
      with tumor stage, histological type, prognostic group, or response to
      preoperative chemotherapy. MATERIALS AND METHODS: Twenty-eight cases of Wilms'
      tumor (two cases with metastasis) and two samples of normal kidney tissue were
      studied using streptavidin-biotin-complex technique. Bcl-X(S/L) expression levels
      were semiquantitatively scored. RESULTS: The expression of Bcl-X(S/L) was
      observed in the majority of cases (60.7%), more often in the blastemal than in
      the epithelial component of Wilms' tumor: 60.7% and 28.6%, respectively (p=0.02).
      There was a statistically significant inverse relationship between Bcl-X(S/L)
      expression and tumor stage (p=0.015). Bcl-X(S/L) was found less frequently in
      high-risk tumors then in tumors with good prognosis (p=0.02). Treated Wilms'
      tumors showed Bcl-X(S/L) expression more often than nontreated tumors, but the
      relationship was not statistically significant (p=0.08). Expression of Bcl-X(S/L)
      was detected in various histological types of Wilms' tumor, but there was no
      statistically significant association (p=0.82) except in cases with diffuse
      anaplasia (p=0.012), which were always negative. No Bcl-X(S/L) immunostaining was
      observed in two cases of metastasis or in one case of bilateral Wilms' tumor.
      CONCLUSION: Our results suggest that the expression of Bcl-X(S/L) protein is
      associated with prognostic group, tumor stage, and presence of anaplasia.

PMID- 15717630
TI  - Ten years' experience in subtotal parathyroidectomy of hemodialysis patients.
AB  - Secondary hyperparathyroidism (SHP) is a frequent complication of long-term
      dialysis patients, and surgical parathyroidectomy remains necessary in patients
      resistant to medical therapy. The present paper reports single center results in
      subtotal parathyroidectomy, presenting diagnostic procedure, indications for
      parathyroidectomy, and postoperative course of metabolic and endocrine disorders.
      Forty-seven patients (25 males and 22 females), aged 25-60 years, regularly
      hemodialyzed between 3-23 years, have undergone parathyroidectomy at our Clinical
      Center during the last 10 years. The patients had plasma iPTH levels 8-45 times
      higher than the top normal limit, high values of alkaline phosphatase, calcemia
      on the upper normal level, and hyperphosphatemia. Radiographic changes
      characteristic for SHP were seen in all patients before parathyroidectomy, and
      the most common were subperiosteal resorptions (100%), bone cysts and periosteal
      neostosis (66%), and extraskeletal calcifications (98%). Enlarged parathyroid
      glands were seen by ultrasound in 62% of patients. All patients manifested
      pruritus and bone pain, 89% of them had myopathy, while other symptoms and signs
      were present in lower proportions. After parathyroidectomy, pruritus and myopathy
      reduced significantly, while pain in bones and joints remained. One patient had
      brown tumor at the maxillary bone that regressed gradually after
      parathyroidectomy. Significant decreases of phosphate and calcium levels were
      recorded in all but two patients on the very first postoperative day. Regular
      peroral and parenteral supplementations of calcium and vitamin D metabolites were
      used, but calcemia was not normalized until the end of the third week of the
      postoperative period. Serum alkaline phosphatase showed an increase after the
      surgery, thereupon a sudden and then slower decrease up to 1 year from the
      surgery. Plasma iPTH levels, checked on the 21st postoperative day, were close to
      the lower normal limit in all but two (4.3%) patients with persistent SHP, who
      required reoperation. In conclusion, subtotal parathyroidectomy was proved as a
      successful and safe treatment for patients with SHP resistant to medical therapy,
      and treatment was followed by improvement of clinical symptoms and metabolic
      disorders.

PMID- 15717631
TI  - IgM-anticardiolipin antibody and vascular access thrombosis in chronic
      hemodialysis patients.
AB  - AIM: Vascular access failure is a major cause of morbidity in chronic
      hemodialysis (HD) patients. Elevated immunoglobulin-M anticardiolipin antibody
      (IgM-aCL) titer is associated with stenosis of vascular access in HD patients.
      The clinical significance of elevated IgM-aCL titer relative to recurrent
      vascular access thrombosis (VAT) in patients with HD is less clear. However,
      little information has been available until now about the clinical influence of
      elevated IgM-aCL titer with recurrent VAT in HD patients from Western countries,
      and no report exists for Taiwan. This study attempted to determine whether
      elevated IgM-aCL titer was associated with recurrent VAT in HD patients. METHODS:
      This study enrolled 483 patients undergoing HD. IgM-aCL titer and hepatitis C
      marker were measured for all subjects. RESULTS: Elevated IgM-aCL titer was
      present in 17.4% (84/483) of patients. There was no association recurrent VAT
      between elevated and normal IgM-aCL titers (P=0.90). Presence of hepatitis C had
      significant differences between elevated and normal IgM-aCL titers (P=0.027).
      CONCLUSIONS: We found no significant differences in recurrent VAT between
      elevated and normal IgM-aCL titer in chronic HD patients. Our results suggest
      recurrent VAT of synthetic or native fistula may not be caused by elevated IgM
      aCL titer in these patients. Presence of hepatitis C may be a cofactor.

PMID- 15717632
TI  - The effect of high-flux hemodialysis on dialysis-associated amyloidosis.
AB  - Amyloidosis is an important cause of mortality and morbidity in patients with end
      stage renal disease (ESRD) undergoing hemodialysis (HD). In this study, depending
      on the idea that the clearance of middle and high molecular weight toxins could
      be improved, we aimed to investigate the effect of high-flux dialyzer on
      clearance of beta-2 microglobulin (beta2-MG) and calcium (Ca) phosphorus (P)
      metabolism in patients under HD treatment. Forty-eight patients with ESRD under
      chronic HD treatment were included in the study. All patients were randomized
      into two groups, and HD was performed with low-flux or high-flux dialyzer for 6
      months. In the high-flux group, the reduction of beta2-MG and P levels during
      dialysis was significantly higher when compared with the low-flux group
      (p<0.001). During the follow-up period, while beta2-MG levels decreased
      significantly in the high-flux group (p<0.05), there was an increase in the low
      flux group (p<0.05). As a result, our findings suggest that use of high-flux
      dialyzer can be an efficient alternative in terms of controlling the clearance of
      beta2-MG and impaired Ca and P metabolism. These beneficial effects of high-flux
      dialyzers are probably mediated by the improved clearance of middle and high
      molecular weight toxins.

PMID- 15717633
TI  - Acute renal failure associated with the use of traditional folk remedies in South
      Africa.
AB  - The use of folk remedies is widespread throughout Africa. Acute renal failure
      (ARF) is one of the most severe, but under-recognized, complications of folk
      remedy use. This report aims to describe the clinical presentation, outcomes, and
      nature of renal injury in patients with folk-remedy-associated ARF. Clinical data
      were evaluated retrospectively in 78 patients with ARF associated with recent
      folk remedy use. ARF was defined as elevated serum urea and creatinine above the
      age-appropriate normal ranges, persistent oligoanuria, worsening renal function
      with time, or need for dialysis. Overall mortality in patients with ARF was 41%.
      Mortality was higher in adults (45.5%) than in infants (36.6%), in patients with
      both renal and liver dysfunction (62.5%) than in those with renal dysfunction
      alone (22.6%), and in HIV-positive (44.4%) versus HIV-negative (34.6%) patients.
      Vomiting (51.3%) and diarrhea (43.6%) were the most frequent presenting symptoms.
      Metabolic acidosis (80.8%) and volume depletion (62.8%) were the most frequent
      clinical findings. The definable causes of ARF were pre-renal (26.9%), acute
      tubular necrosis (ATN; 26.9%), hepatorenal syndrome (6.4%), urinary tract
      infection/sepsis (7.7%), and primary renal disorders (7.7%). Twenty-seven
      patients had concomitant medical conditions unlikely primarily related to folk
      remedy ingestion. In conclusion, ARF occurring after use of folk remedies in
      South Africa is associated with significant morbidity and mortality. The most
      common contributors to ARF in this setting are volume depletion and ATN.
      Significantly, although a proportion of patients have underlying systemic or
      renal conditions that may contribute to renal dysfunction, in the majority of
      patients, folk remedy use appears to be the most likely proximate cause. In view
      of the large numbers of Africans living abroad, more widespread awareness of this
      important clinical problem needs to be raised.

PMID- 15717635
TI  - Interleukin 1 receptor antagonist and tumor necrosis factor-alpha gene
      polymorphism in patients with end-stage renal failure.
AB  - End-stage-renal disease (ESRD) is a final result of various etiologies.
      Prognostic indicators leading to ESRD in chronic kidney diseases have been
      studied extensively, of which, genetic factors remain a subject of great concern.
      Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are potent
      proinflammatory cytokines that are involved in several chronic kidney diseases.
      Studies on cytokine gene polymorphism have revealed important information about
      the role of genetic factors in disease susceptibility and severity. Gene
      polymorphism of interleukin-1 receptor antagonist (IL-1ra) and TNF-alpha were
      determined in 297 ESRD patients and in 145 normal healthy controls. IL-1ra gene
      polymorphism was characterized as a variable number of tandem repeats of a 86 bp
      sequence within intron 2. Five alleles were identified and were designated as
      IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5, corresponding to 4,2,5,3, and 6
      repeats, respectively. A polymorphism in the promoter region of the TNF-alpha
      gene was also studied. This polymorphism involved a guanidine to adenosine
      transition at position -308 and was designated as TNF1 (- 308 G) and TNF2 (-308
      A). The genotypes and allele frequencies were compared between patients and
      control group. The distributions of genotypes of IL-1ra and TNF-alpha did not
      differ significantly between ESRD patients and normal controls. Analysis of
      allele frequencies revealed a trend toward an increase in IL1RN*2 frequency (7.5%
      versus 3.8 %, p=0.064) and noncarriage of TNF2 in the patient group (7.2% versus
      11.0%, p=0.076) when compared with the control group. When both alleles were
      considered together, the patient group had a significantly higher frequency of
      carriage of IL1RN*2 in combination with noncarriage of TNF2 (p=0.0468). We
      conclude that carriage of IL-1RN*2 and noncarriage of TNF2 allele appear to be
      poor prognostic factors in patients suffering from various chronic renal diseases
      that eventually enter end-stage renal failure.

PMID- 15717634
TI  - Multivariate analysis of prognostic factors and effect of treatment in patients
      with IgA nephropathy.
AB  - BACKGROUND: Although the clinical and histological prognostic factors of IgA
      nephropathy have been investigated in detail, the value of treatment in terms of
      renal outcome is not well understood. METHODS: The authors examined data from 237
      patients with IgA nephropathy (age 31.4+/-13.5 years, mean+/-SD) who had been
      followed-up for at least six months (follow-up periods, 62.3+/-45.5 months). The
      authors initially tested the significance of prognostic factors (age, sex,
      systolic blood pressure, proteinuria, serum creatinine, and histological
      severity) and treatment strategies (steroid therapy, renin-angiotensin system
      inhibitors and tonsillectomy) on renal outcome with univariate analysis, then
      evaluated the findings using the Cox proportional hazards model. RESULTS:
      Univariate and multivariate analyses showed that among the prognostic variables,
      a high level of serum creatinine at renal biopsy, large amounts of proteinuria,
      and extensive histological injury were significant risk factors for end-stage
      renal failure. Kaplan-Meier analysis showed that the renal survival rates
      associated with these factors were significantly poorer depending on their
      severity. Univariate analysis revealed that tonsillectomy was the only
      significant treatment that contributes to the maintenance of renal survival.
      Moreover, urinary abnormalities disappeared at a significantly higher frequency
      when patients were treated by tonsillectomy. The Cox proportional hazards model
      showed that steroid therapy independently contributed to improve renal prognosis
      in addition to tonsillectomy, and the hazard ratios were 0.26 (95% CI, 0.07 to
      0.93) and 0.37 (95% CI, 0.14 to 0.99), respectively. CONCLUSION: Steroid therapy
      and tonsillectomy can independently improve renal outcome in patients with IgA
      nephropathy.

PMID- 15717636
TI  - Monitoring the content of reticulocyte hemoglobin (CHr) as the progression of
      anemia in nondialysis chronic renal failure (CRF) patients.
AB  - BACKGROUND: We previously showed that the content of reticulocyte hemoglobin
      (CHr) is a reliable measure of iron status in chronic dialysis patients with
      erythrocytopoiesis. The CHr was significantly correlated with conventional
      parameters of iron deficiency in dialysis patients. We attempted to utilize the
      measurement of CHr levels to monitor iron status and clarify the changes in iron
      levels that occur as renal anemia progresses in patients with chronic renal
      failure (CRF). METHODS: We measured CHr, iron parameters, and the intrinsic
      erythropoietin (EPO) concentration in nondialysis CRF patients who visited our
      outpatient clinic (n=211). Iron deficiency was defined according to the
      transferrin saturation (TSAT) and ferritin levels. Conventional red blood cell
      parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer
      Medical, USA). RESULTS: The mean CHr value of the nondialysis CRF patients
      (creatinine clearance less than 70 mL/min) was 32.3 pg, which was not
      significantly different from that of the dialysis patients. Significant
      correlations were found between CHr and ferritin levels (r=0.042, p<0.0403) and
      CHr and TSAT levels (r=0.040, p<0.0157). A positive correlation was observed
      between the CHr and serum creatinine levels. Nondialysis CRF patients treated
      with recombinant human EPO (rHuEPO) at a dose of 24,000 U/month exhibited lower
      CHr levels, compared with those of other patients who received less than 24,000
      U/month. CONCLUSION: CHr is an easily measurable and trustworthy marker of iron
      status in nondialysis CRF patients. Moreover, the CHr level was also sensitive to
      iron alterations in nondialysis CRF patients receiving rHuEPO treatment, and
      thus, the CHr value could likely provide useful information regarding the need
      for iron supplementation.

PMID- 15717637
TI  - Nephropathy and retinopathy in type 2 diabetic patients living at moderately high
      altitude and sea level.
AB  - BACKGROUND: High-altitude-induced hypoxia results in various diseases, such as
      chronic mountain sickness and high altitude retinal edema, and may affect
      severity and incidence of some cardiovascular diseases. In order to evaluate the
      effects of moderately high altitude on diabetic nephropathy and retinopathy, a
      cross-sectional study was planned. MATERIAL METHOD: Long-term type II diabetic
      residents of sea level (n=75, 38 male, 37 female, mean age 51.9+/-10.5 in Trabzon
      and Zonguldak cities) and moderately high altitude (h = 1,727 m, n = 73, 28 male,
      45 female, mean age 48.3+/-12.1, Van city) were compared. RESULTS: No difference
      was observed in terms of age, gender, diabetes duration, body mass index,
      smoking, systolic, diastolic, and mean arterial blood pressure values, serum
      glucose levels, cholesterol, high-density lipoprotein (HDL)-cholesterol, low
      density lipoprotein (LDL)-cholesterol, hemoglobin, HbA1C, hypertension control,
      or blood pressure medications and retinopathy incidence. Mean 24 h protein
      excretion (210.0+/-139.9, 127.8+/-112.1 mg; P=0.00), proteinuria prevalence
      (57.5% versus 33.3%, p=0.003), and serum creatinine levels (1.04+/-0.22 versus
      0.84+/-0.21, p = 0.00) were significantly higher in the highlanders, glomerular
      filtration rate (GFR) was significantly lower in sea level (SL) patients (90.9+/
      26.5 versus 83+/-21.1, p=0.05). CONCLUSION: Tendency to diabetic nephropathy as
      indicated by higher proteinuria and creatinine levels is increased among type 2
      diabetic patients living at moderately high altitude. Prospective studies are
      needed to confirm these findings.

PMID- 15717638
TI  - Lercanidipine in patients with chronic renal failure: the ZAFRA study.
AB  - OBJECTIVE: The objective was primary to evaluate the safe use of a new calcium
      channel blocker, lercanidipine, in patients with chronic renal failure (CRF). The
      secondary objective was to study the protective effect of calcium channel blocker
      on renal function in CRF patients previously treated with ACE inhibitors or
      angiotensin receptor blockers. DESIGN AND METHODS: The study recruited 203 CRF
      patients (creatinine >1.4 mg/dL for males, creatinine > 1.2 mg/dL for females, or
      creatinine clearance <70 mL/min). All patients were receiving ACE inhibitors
      (63.4%) or angiotensin II antagonist (36.6%) therapy, but they had higher blood
      pressure than recommended for CRF (130/85 mmHg). No patients were under diuretic
      treatment. Patients were clinically evaluated 1, 3, and 6 months after starting
      treatment with lercanidipine. Samples for urine and blood examination were taken
      during the examination. When needed, a third drug was added to the treatment,
      excluding diuretics. Creatinine clearance was measured using 24 h urine
      collection. RESULTS: 175 patients rendered valuable for the study (age 63.9+/
      11.9 years, 52.9% males and 47.1% females). Blood pressure (BP) significantly
      decreased from 162+/-17/93+/-8.3 mmHg to 132+/-12/78+/-6 mmHg. 89.2% of patients
      showed a significant BP reduction, and 58.1% achieved optimal BP control (<130/85
      mmHg). Seven patients (3.4%) showed untoward effects. Not one case of edema was
      detected, and the prevalence of adverse effects related to vasodilatation was
      extremely low (three patients, 1.48%). Plasmatic creatinine did not change (1.9+/
      0.5 baseline versus 1.9+/-0.6 mg/dL), but creatinine clearance increased at the
      end visit (41.8+/-16.0 baseline versus 45.8+/-18.0 mL/min, p=0.019). Plasmatic
      cholesterol also decreased from 221+/-46 to 211+/-35 mg/dL (p=0.001).
      CONCLUSIONS: Lercanidipine showed a high antihypertensive effect in CRF patients.
      It has a good tolerability profile and showed an interesting effect on plasmatic
      lipids. An improvement in renal function, measured through creatine clearance,
      was detected.

PMID- 15717639
TI  - Renal artery stenosis is not associated with the development of acute renal
      failure following coronary artery bypass grafting.
AB  - BACKGROUND: Acute renal failure (ARF) is a frequent complication of coronary
      artery bypass grafting (CABG) surgery and is strongly associated with
      perioperative morbidity and mortality. We hypothesized that renal artery stenosis
      (RAS), causing occult renal ischemia, may be an important factor contributing to
      development of ARF after CABG surgery. METHODS: Preoperative and intraoperative
      data on 798 consecutive adult patients undergoing CABG surgery with
      cardiopulmonary bypass from February 1, 1995 to February 1, 1997 (who had also
      undergone an abdominal aortogram for the evaluation of RAS) were recorded and
      entered into a computerized database. The development of ARF was defined as a
      rise in serum creatinine of 1 mg/dL (88.4 micromol/L) above baseline
      postoperatively. The association between the presence of renal artery stenosis
      together with preoperative and intraoperative variables and the development of
      ARF was assessed by multivariate logistic regression. RESULTS: A total of 798
      patients underwent isolated coronary bypass grafting, of which 18.7% demonstrated
      50% or more RAS. ARF developed in 82 patients (10.2%), of which three (0.3%)
      required dialysis support. The mortality for patients who developed ARF was 14%
      (OR 15, P=0.0001) compared to 0.2% among those who did not develop ARF. The
      presence of renal artery stenosis of any severity ranging from unilateral 50% RAS
      to bilateral 95% RAS was not associated with the subsequent development of ARF.
      CONCLUSIONS: The development of ARF following CABG surgery is associated with
      high mortality. The presence of RAS does not appear to increase the risk for
      developing ARF.

PMID- 15717640
TI  - Hepatitis G virus infection in hemodialysis patients from urban Delhi.
AB  - This study was designed to evaluate the seroprevalence of hepatitis G virus (HGV)
      infection, its impact, and its relationship with other hepatotropic viruses among
      chronic renal failure patients undergoing hemodialysis at the Lok Nayak Hospital,
      New Delhi. The study group consisted of 100 consecutive cases of patients with
      chronic renal failure undergoing hemodialysis and equal healthy controls matched
      for age and sex. The patients were included on the basis of detailed history,
      clinical examination, and liver function profile. HGV RNA was detected in serum
      samples of all patients as well as of healthy controls using nested reverse
      transcription polymerase chain reaction (RT-PCR). The primers used were derived
      from the NS3 helicase region of the viral genome. Serological assay was used for
      screening the viral markers for hepatitis B and C (HbsAg and Anti HCV). A history
      of blood transfusion was recorded in 65% of the cases. HGV RNA was detected in
      only six out of 100 (6%) cases of chronic renal failure. The seroprevalence of
      HCV infection was detected in 27 (27%), while HBV infection was seen in 10 (10%)
      out of 100 cases. The mixed infection of HGV and HCV was seen in 33.3% (two out
      of six) of the chronic renal failure cases, while the coinfection between HGV and
      HBV was not observed. In the 100 cases of healthy controls, HGV RNA was detected
      in only three (3%) subjects. Serological markers for Anti HCV antibody and HbsAg
      were positive in only one (1%) and two (2%) of the subjects, respectively. The
      seroprevalence of HGV infection in chronic renal failure was found to be
      statistically nonsignificant when compared to that of healthy controls. Also,
      there was no difference in clinical course and liver function profile of HGV
      positive and HGV-negative cases. However, alanine aminotransferase (ALT) was
      significantly out of range in HCV-positive patients compared with HCV-negative
      patients. The presence of HGV infection reflected a postparental exposure to
      blood and blood-contaminated products in hemodialysis patients. It is suggested
      that HGV infection in cases of chronic renal failure is unlikely to influence the
      course of the disease and may be considered an innocent bystander.

PMID- 15717641
TI  - Mutations of the PKD2 gene in Taiwanese patients with autosomal dominant
      polycystic kidney disease.
AB  - BACKGROUND: Mutation analysis in the context of clinical phenotypes helps clarify
      the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). Over 78
      PKD2 gene mutations have been reported in the literature, but few have been
      described from an Asian population. This study attempted to characterize PKD2
      mutations and their clinical implications among Taiwanese. METHODS: Twenty
      unrelated ADPKD patients with uncharacterized genotypes were screened for
      mutations in the PKD2 gene via single-strand conformation polymorphism (SSCP) of
      PCR products from genomic DNA, using previously reported PCR conditions and
      primers. RESULTS: This study identified two novel mutations (C681A and 2136
      2137delG) and one mutation (C2407T) previously reported in a Cypriot family.
      Overall, we found PKD2 mutations in 15% (three out of 20) of the ADPKD patients
      screened. The mutations included two nonsense mutations (Y227X and R803X) and one
      frameshift mutation (712-715X) that could all lead to premature termination of
      translation. The locations of mutations in this study spanned the entire PKD2
      gene on exons 2, 11, and 13 without clustering and did not influence the renal
      disease severity. CONCLUSIONS: The study identified two novel mutations and one
      recurrent mutation of the PKD2 gene in 20 Taiwanese patients. The characteristics
      of the mutations in this study resemble those reported among Western populations.

PMID- 15717642
TI  - Effect of fenoldopam mesylate in critically ill patients at risk for acute renal
      failure is dose dependent.
AB  - BACKGROUND: Acute renal failure (ARF) is common and difficult to prevent,
      especially in intensive care unit (ICU) patients with cancer. Therapeutic trials
      with various agents have generally been ineffective in preventing ARF. We
      describe the effects of two different doses of the dopamine DA-1 receptor agonist
      fenoldopam mesylate on renal function in a series of critically ill cancer
      patients at risk of developing ARF. METHODS: We performed a retrospective chart
      review of 100 consecutive patients who received fenoldopam mesylate for at least
      72 h in the medical and surgical ICUs of The University of Texas M. D. Anderson
      Cancer Center who were at risk of developing ARF. Eighteen patients received low
      dose fenoldopam mesylate (< or =0.05 microg/kg/min). The remaining 82 patients
      received high-dose fenoldopam mesylate (0.07-0.1 microg/kg/min). Data were
      collected relating to drug dosage, patient demographics, severity of illness, and
      indices of renal function. RESULTS: Patients were moderately ill, with a mean
      APACHE II score of 18+/-6 at initiation of fenoldopam infusion. Eighty-five
      percent of patients had at least two risk factors for the development of ARF, and
      20% had four. For the group overall, the incidence of ARF was 13%, and the
      hospital mortality rate was 37%. When compared with the low-dose group, patients
      who received high-dose fenoldopam had a significantly shorter ICU length of stay
      despite a significantly higher APACHE II score (p=0.01). The high-dose group also
      had a highly significant decrease in serum creatinine levels at 72 h (p=0.005).
      CONCLUSIONS: These data support the hypothesis that fenoldopam mesylate may
      provide a degree of dose-dependent renal protection in cancer patients with early
      acute renal failure.

PMID- 15717643
TI  - Apoptosis and proliferating cell nuclear antigen in lupus nephritis (class IV)
      and membranoproliferative glomerulonephritis.
AB  - BACKGROUND: The role of apoptosis in the pathogenesis of renal diseases has not
      been clearly established. Proliferating cell nuclear antigen (PCNA) is also a
      proliferation marker. In this study, we investigated the relationship between
      clinical course and PCNA apoptosis on baseline renal biopsy in patients with
      Lupus nephritis (LN) and membranoproliferative glomerulonephritis (MPGN).
      METHODS: Thirty-nine patients with proliferative glomerulonephritis [lupus
      nephritis (LN)[21] and MPGN[18]] were included in this study. PCNA and apoptosis
      on renal biopsies were detected by immunohistochemical and terminal
      deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) methods,
      respectively. We calculated the ratios of intraglomerular apoptotic cells and
      PCNA positive cells per glomeruli, and total numbers of apoptotic tubular cells
      and PCNA positive tubular cells among the 100 tubular cells, and PCNA positive
      cell and apoptotic cell on two different tubulointerstitial areas (40 x 10).
      RESULTS: In LN: Apoptotic indexes of glomerulus and tubulus were 1.08+/-0.49 and
      3.71+/-1.38, respectively. PCNA positivities were found at 16.76+/-11.34%,
      46.57+/-22.54%, and 40.28+/-23.14% on glomerulus, tubulus, and interstitium,
      respectively. The activity index was 11.23+/-3.41, and the chronicity index was
      3.81+/-1.99. In MPGN: Apoptotic indexes were found at 0.83+/-0.25 and 3.55+/-1.75
      on glomerulus and tubulus, respectively. PCNA positivities were found at 21.33+/
      18.42%, 35.5+/-25.99%, and 34.66+/-26.84% on glomerulus, tubulus, and
      interstitium, respectively. In controls, apoptosis was not found. In LN: PCNA
      positivity on tubulus and interstitium were correlated with the activity index (r
      = 0.768, p < 0.001, r = 0.721, and p < 0.001, respectively). Glomerular PCNA and
      apoptosis on interstitium and glomerulus were not correlated with the activity
      index. The activity index also was not correlated with creatinine clearance and
      daily proteinuria (p = 0.35 for both). At the end of the first year, patients
      with recovered or stabilized renal function had higher interstitial and tubular
      PCNA than others in G1 and G2. CONCLUSION: It can be said that expression of PCNA
      on renal biopsy was correlated with activity indexes in LN. PCNA may be a
      prognostic indicator in MPGN and LN. However, apoptosis does not have a
      predictive value for MPGN and LN.

PMID- 15717644
TI  - Comparative analysis of the renoprotective effects of pentoxifylline and vitamin
      E on streptozotocin-induced diabetes mellitus.
AB  - BACKGROUND: Oxidative stress (OxS) induced by diabetes plays an important role in
      the development of diabetic nephropathy. Studies have shown that antioxidants are
      beneficial in its reduction. Vitamin E has been documented as providing the most
      improvement in the antioxidative status. Recently, pentoxifylline (PTX) has been
      proposed to have antioxidant properties. AIM: The aim of the study was to assess
      the ability of two antioxidants to reduce lipid peroxidation and renal
      hypertrophy in vivo. METHODS: Diabetes was induced by streptozotocin (STZ) in
      rats. Treatment groups were divided as follows: healthy (H), diabetic without
      treatment (STZ), PTX treated group (STZ+PTX), and vitamin E supplemented (STZ+E)
      group. At 8 weeks, kidneys were removed; one was homogenized to quantify
      lipoperoxide levels (LPOS), and the other was used to study the morphological
      changes by electron microscopy (EM). Additionally, plasma total antioxidant
      activity (TAA) was quantified. RESULTS: A reduction in LPOS was observed in both
      groups: PTX and vitamin E with regard to STZ group. PTX increased TAA compared to
      STZ+E, which restored it to its normal values. However, both treatments reduced
      the LPO/TAA ratio to lower basal levels; hence, similar results were obtained in
      terms of correcting functional parameters. Structural changes in STZ rats
      included a glomerular membrane thickening, podocyte flattening, as well as loss
      of fenestration in the endothelial layer. All these changes were less aggressive
      for treated rats. CONCLUSIONS: Vitamin E and PTX have potential therapeutic
      properties that may help to retard the rate of deterioration of diabetic kidneys.

PMID- 15717645
TI  - Psoriatic nephropathy--does an entity exist?
AB  - Psoriasis is an immune-mediated chronic inflammatory disorder of the skin.
      Association with kidney disease has been debated for a long time. Secondary renal
      amyloidosis in psoriatic arthropathy and drug-induced renal lesions secondary to
      methotrexate or cyclosporine are accepted accompaniments of psoriasis. IgA
      nephropathy is also known to occur in psoriatics. We report three interesting
      cases of renal involvement in long-standing established psoriasis on topical
      therapy alone. The patients presented with hypertension, significant proteinuria,
      hypoalbuminemia, and dyslipidemia. Kidney biopsies revealed
      "mesangioproliferative glomerulonephritis with IgA nephropathy," "focal
      proliferative glomerulonephritis," and "membranous glomerulonephropathy." The
      former two had marked active urinary sediment. Patients improved on prednisolone
      and angiotensin-converting enzyme inhibitors. Contrary to the belief that renal
      involvement in psoriasis is coincidental, we propose that kidney disease may be a
      common accompaniment of psoriasis, which may be labeled as "psoriatic
      nephropathy" or "psoriatic kidney disease." The exact mechanism of this entity is
      yet to be elucidated.

PMID- 15717646
TI  - Use of quantitative ultrasound of the hand phalanges in the diagnosis of two
      different osteoporotic syndromes: Cushing's syndrome and postmenopausal
      osteoporosis.
AB  - The aim of this study was to assess the ability of the quantitative ultrasound of
      the hand phalanges to detect different types of osteoporosis resulting from
      different pathogenetic mechanisms. For this purpose, postmenopausal and
      glucocorticoid-induced osteoporosis was studied. Thirteen female patients with
      Cushing's syndrome (CS) resulting from pituitary-dependent bilateral adrenal
      hyperplasia (10 patients) and from adrenal adenoma (3 patients), and 32
      postmenopausal osteoporotic (OP) women, were examined. The two groups of patients
      were comparable for body mass index (BMI), but CS patients were significantly
      younger than OP ones (CS 44.5+/-11.6; OP: 73.9+/-3.6). All the patients had
      femoral neck bone mineral density (BMD) T-score less than -2.0. Cushing patients
      had a femoral neck BMD similar to that of OP patients (CS: 603+/-66 mg/cm2; OP:
      628+/-69 mg/cm2; p=0.19). In contrast, amplitude-dependent speed of sound (AD
      SoS) was significantly higher in CS patients than in OP patients (CS: 1997+/-91
      m/s; OP: 1707+/-114 m/s; p<0.0001). By adjusting DXA and ultrasound parameters
      according to age, femoral neck BMD was significantly lower in CS patients and AD
      SoS remained significantly higher than in OP patients. These findings indicate
      that these two different kinds of osteoporosis can be distinguished by
      ultrasonography and that ultrasound parameters alone cannot be used for
      evaluating skeletal status in CS patients.

PMID- 15717647
TI  - Thyroid volume and urinary iodine excretion in the schoolchild population of a
      Northwestern Italian sub-Alp metropolitan area.
AB  - Iodine deficiency is recognised as a major preventable public-health worldwide
      problem. The aim of this study is to assess local reference values for thyroid
      volume, and give a snapshot of the epidemiology of goiter and iodine nutritional
      status of the Turin schoolchild population. Sonographic thyroid volume and median
      urinary iodine excretion were obtained in 1067 schoolchildren aged 11-15 yr
      resident in Turin for more than 5 yr to assess both goiter prevalence and iodine
      intake. All the subjects were asked to fill in a questionnaire about their life
      habits. Anamnestic and anthropometric data, thyroid volume by both bimanual
      palpation and ultrasonography were assessed, and spot urinary iodine samples were
      collected. The results show that the median urinary iodine concentration is 113.1
      microg/l and the prevalence of goiter <5%, indicating this area as iodine
      sufficient. Nevertheless, 40.5% of the schoolchild population has urinary iodine
      levels lower than the cut-off level recommended as iodine-sufficiency.
      Interestingly, the high relative prevalence of ultrasound features of autoimmune
      thyroid disease suggests autoimmune-thyroiditis as a frequent thyroid disease in
      Turin schoolchildren. As no active programs of salt, milk or water iodisation
      have ever been carried out, a silent iodine prophylaxis has probably occurred in
      the city. Despite a sufficient median urinary iodine excretion, a focused program
      of iodine prophylaxis should be developed due to the presence of a large rate of
      iodine-deficient population.

PMID- 15717648
TI  - Gonadotropin response to clomiphene and plasma leptin levels in weight recovered
      but amenorrhoeic patients with anorexia nervosa.
AB  - Anorexia nervosa (AN) is a state of leptin and gonadotropin deficiency. Leptin
      levels are decreased in normal weight women with hypothalamic amenorrhea and
      leptin may be a sensitive marker of overall nutritional status. The aim of the
      study is to provide additional information on plasma leptin levels and on
      gonadotropin responses after clomiphene testing in patients with AN who recovered
      weight but were still amenorrheic. We evaluated 17 patients with AN, female age
      20+/-1.2 yr who reached goal weight [body mass index (BMI) 14.9+/-0.5 to 19.3+/
      0.4 kg/m2]. At diagnosis serum leptin levels were 2.2+/-0.1 microg/l while after
      behavioural therapy and hypercaloric diet for 6-12 months serum leptin levels
      rose to 6.4+/-1.4 microg/l significantly lower compared with those in the control
      (no.=10, age 28+/-6.2 yr, BMI 21.1+/-0.3 kg/m2, leptin 9.3+/-0.7 pg/l; p<0.05).
      None of the patients resumed spontaneous menstrual cycles after weight gain. They
      were tested with a 10-day administration of clomiphene citrate. All had a
      significant rise in LH secretion (from 1.7+/-0.3 IU/l to 8.3+/-0.9 IU/l, p<0.01)
      and serum estradiol levels (from 19.0+/-5.4 to 937.7+/-241.2 pg/ml, p<0.03). Nine
      out of 17 patients menstruated after clomiphene. Serum leptin levels were not
      different in those who menstruated from those who did not (6.4+/-1.4 to 6.8+/-1.4
      microg/l, p>0.05). Body compositon was studied in 12 additional carefully matched
      patients with AN who recovered weight. Six of them resumed spontaneous menstrual
      cycles. Neither BMI, body fat, nor leptin appeared as significant determinants of
      menstrual status. In conclusion, relative hypoleptinemia persists, independent of
      fat mass, in weight recovered patients with AN. A normal response to clomiphene
      in weight-recovered yet still amenorrhoeic patients with AN, offers reassurance
      that the axis is intact and that the problem lies in the hypothalamus. It is
      reasonable to believe that nutritional disturbances, fat intake and persisting
      psychological factors still affect plasma leptin levels and reproductive
      functions in weight-recovered patients with amenorrhea.

PMID- 15717649
TI  - Serum adiponectin in women with polycystic ovarian syndrome and its relation to
      clinical, metabolic and endocrine parameters.
AB  - Several studies have demonstrated that low levels of serum adiponectin are
      present in obesity, insulin resistance, hypertension and hyperlipidemias. The aim
      of our study was to determine whether serum adiponectin level is different
      between patients with polycystic ovarian syndrome (PCOS) and control subjects. We
      also investigated relationships between various cardiovascular risk factors,
      levels of serum adiponectin and other hormones, such as androstendione,
      testosterone, estradiol, DHEAS, sex hormone binding globulin (SHBG), and leptin.
      We also analysed the correlation between serum adiponectin and free androgen
      index. Ninety-one women with clinical diagnosed PCOS and 53 healthy control
      subjects, carefully matched by body mass index (BMI) and age, were enrolled in
      the study. The fasting blood samples were obtained and all participants underwent
      an oral 75 g glucose tolerance test. The prevalences of impaired glucose
      tolerance (IGT), hypertension and hypertriglyceridemia were higher in the PCOS
      group. PCOS women had increased androgen concentrations and higher free androgen
      index and decreased level of serum SHBG. Lower serum adiponectin concentrations
      were observed among cases than in controls (median 13.7 microg/ml vs 17.8
      microg/ml, p<0.001) despite being matched by BMI. In the PCOS group adiponectin
      levels correlated significantly with: BMI (r=-0.32, p=0.002), waist circumference
      (r=-0.32, p=0.003), waist-to-hip ratio (WHR, r=-0.38, p=0.001), triglycerides (r=
      0.31, p=0.007), SHBG (r=0.30, p=0.003) and free androgen index (r=-0.29, p=0.02).
      In contrast, the adiponectin level does not appear to be related to total
      testosterone, DHEAS and leptin levels. The adiponectin and SHBG levels were found
      to be decreased in PCOS women with IGT compared to PCOS women with normal glucose
      tolerance, but after adjustment by BMI or WHR, the differences were no longer
      statistically significant. To exclude a possible confounding effect due to a
      higher prevalence of IGT in the PCOS group, this comparison was repeated for the
      subgroup of 58 PCOS women and 48 control women after excluding those with IGT.
      Neither adiponectin nor SHBG were significantly different between those
      subgroups. Multiple regression analysis revealed that serum adiponectin
      concentrations were best predicted by WHR, free androgen index and presence of
      IGT when all patients were considered. In PCOS subjects, the only independent
      predictor of adiponectin concentrations was glucose tolerance status.
      CONCLUSIONS: Lower adiponectin levels were observed in PCOS group than in control
      women, and these differences were probably due to higher prevalence of IGT in
      these cases.

PMID- 15717650
TI  - Indexes of abdominal adiposity in patients with type 2 diabetes.
AB  - OBJECTIVE: To assess the relationship of waist circumference and weight/height
      ratio with height, and their association with components of the metabolic
      syndrome, in Type 2 diabetic patients. DESIGN: multicenter cross-sectional survey
      on a cohort enrolled in a prospective observational study. SUBJECTS: 13,232
      patients (6816 women and 6416 men) with Type 2 diabetes, not currently affected
      by macrovascular complications. MEASUREMENTS: height, weight, waist and hip
      circumference, waist/hip and waist/height ratios. RESULTS: waist circumference
      was significantly correlated with height after adjustment for potential
      confounders (adjusted r=0.19 and 0.23 in women and men, respectively), while
      waist/height ratio showed an inverse correlation with height (r=-0.14 and -0.15,
      respectively). Elevated waist/height ratio was more predictive of hypertension
      and hypertriglyceridemia, than waist circumference or waist/hip ratio.
      CONCLUSIONS: Waist circumference is correlated with height; thresholds for waist
      circumference could need adjustment for height. Waist/height ratio, although
      inversely correlated with height, could be a better predictor of abnormalities
      associated with abdominal adiposity than waist circumference alone.

PMID- 15717651
TI  - Response of the hypothalamic-pituitary-adrenal axis to small dose arginine
      vasopressin and daily urinary free cortisol before and after alprazolam pre
      treatment differs in obesity.
AB  - OBJECTIVE: Arginine vasopressin (AVP) has a central role in the response of the
      hypothalamic-pituitary-adrenal (HPA) axis to stress conditions. A low dose of AVP
      has been shown to have a modest, but significant effect on ACTH response in
      normal weight subjects. The aim of this study was to test the response of the HPA
      axis in obese subjects in order to assess eventual primary neuroendocrine
      alterations, previously demonstrated by using AVP combined with corticotropin
      releasing hormone (CRH). In addition, given its central inhibitory action on the
      HPA axis, we investigated whether the suppressive capacity of alprazolam (APZ)
      pretreatment on the hormone response to low-dose AVP challenge and daily urinary
      free cortisol (UFC) excretion rate may be altered in the presence of obesity.
      DESIGN: Fifteen overweight or obese women and eight normal-weight controls
      randomly underwent two low-dose AVP tests (0.3 UI iv bolus), one without (AVP
      test) and the other preceded by APZ administration (0.5 mg at midnight and 0.5 mg
      90 min before the test in the morning at 08:30 h) (APZ/AVP test). Blood samples
      for ACTH and cortisol assay were obtained at baseline and throughout each test.
      The day before each test, 24h-UFC/ creatinine was also mea-sured. RESULTS: Basal
      ACTH levels were similar in the two groups, whereas cortisol concentrations were
      significantly lower in the overweight/obese group. Overweight/obese women had
      higher ACTH and cortisol responses to the AVP tests and significantly greater
      hormone inhibition after APZ than controls. In both groups, AVP-induced delta
      peak cortisol values before and after APZ pre-treatment were significantly
      correlated. Body fat distribution had no effect on the HPA axis response to AVP
      either before or after APZ. Moreover, APZ decreased 24h-UFC/creatinine values
      unsignificantly in controls and by approximately 50% in the overweight/obese
      subjects. These changes were unrelated to the cortisol response to the AVP test
      before and after APZ pretreatment. On the other hand, percent changes of 24h
      UFC/creatinine after APZ were negatively related to the body mass index (BMI) but
      positively with waist circumference values, which indicates that the abdominal
      obesity phenotype may counteract the 24 h-UFC/creatinine that would be expected
      on the basis of BMI values. CONCLUSIONS: Our data further support the concept
      that in women obesity may represent a condition of hyperresponsiveness or
      hypersensitivity of the HPA axis to neuroendocrine stimuli, which appear to be
      independent of feedback control. In addition, the data on the inhibiting capacity
      of APZ on UFC excretion confirm that the alterations of the HPA axis in obesity
      is particularly evident in the abdominal phenotype.

PMID- 15717652
TI  - Are subjects with erectile dysfunction aware of their condition? Results from a
      retrospective study based on an Italian free-call information service.
AB  - The aim of the study was to analyse the socio-demographic and epidemiological
      characteristics of the Italian male population affected by sexual disturbances.
      Men complaining of erectile dysfunction (ED) who called the Pfizer program "Man
      and Woman in Health" between April 18th 2001 and May 27th 2002 and asked for
      information about their medical condition, were interviewed by trained doctors
      using a computer-assisted questionnaire. 16007 out of 25018 calls were considered
      for statistical analysis. Mean age of callers was 48.8+/-14.2 yr, reporting ED in
      83% of cases. In the majority of men ED was severe (58%) and lasting more than 3
      yr (25%). Multivariate analysis revealed that diabetes, depression, prostate
      surgery, heart disease, neurological disorders, liver and renal diseases were all
      significant and independent contributors to the degree of erectile impairment
      adjusted for age (p<0.001). The principal concomitant medications were anti
      hypertensive (23%), antidiabetic (9%) and cardiovascular agents (6%). Cigarette
      smoking was present in 24%. On directed questioning of the caller, anxiety and
      distress were perceived as the most frequent causes of ED (42%) across all age
      groups, followed by the presence of concomitant disease/s (26%) especially in
      aging men. Also, a large number of men (41 %) with severe ED waited for more than
      3 yr before looking for medical referral. Interestingly, only 19% had ever tried
      any specific medication for ED. These data indicate that 5 yr after worldwide
      approval and release of sildenafil, ED is still largely undiagnosed and under
      treated, possibly because it is still perceived as a condition mainly due to
      distress or advancing age and therefore not deserving medical referral. Effective
      prevention of ED commences with better awareness of the pathological causes by
      the population and modification of risk factors by the doctors.

PMID- 15717653
TI  - Video assisted prophylactic thyroidectomy and central compartment nodes clearance
      in two RET gene mutation adult carriers.
AB  - Activating point mutations of RET gene have been demonstrated to be causative of
      the familial form of medullary thyroid cancer (MTC), both isolated (FMTC) and
      associated to other endocrine neoplasia [multiple endocrine neoplasia (MEN) 2A
      and 2B]. In RET gene mutation carriers, who are prone to developing MTC,
      prophylactic thyroidectomy is recommended to obtain their definitive cure. The
      simultaneous excision of the central node compartment is mandatory when the
      stimulation pentagastrin test for serum calcitonin is positive. Although the
      minimally invasive video assisted thyroidectomy (MIVAT) is nowadays currently
      adopted in many centers, it has never been employed for the prophylactic
      thyroidectomy of RET gene mutation carriers. The fear of obtaining an incomplete
      lymphadenectomy of the central compartment was the main reason for this
      reluctance. Since RET gene mutation carriers have often normal thyroid volume
      and, if involved, small lymph nodes, they indeed represent the best candidates to
      this approach especially when considering that they are usually young and
      concerned about the cosmetic results and the period of hospitalization. The
      excellent results obtained by MIVAT in the last few years induced us to propose
      this procedure together with a central compartment lymphadenectomy to 2 RET gene
      mutation carriers recently found by genetic screening. As assessed by a negative
      pentagastrin stimulation test performed after 6 months from the MIVAT, they were
      definitively cured without any surgical complication with the exception of a
      transient hypoparathyroidism. They showed a great satisfaction for both the
      cosmetic results and the very short period of hospitalization, thus supporting
      the idea that MIVAT can be used in association with the central node dissection
      for the prophylactic treatment of RET mutation gene carriers whose thyroid volume
      is still normal.

PMID- 15717654
TI  - A patient presenting with spinal cord compression who had two distinct follicular
      cell type thyroid carcinomas.
AB  - A 61-yr-old woman presented with complaints of weakness and pain in her legs. A
      magnetic resonance imaging showed a 3 x 5.6 x 7.8 cm mass lesion destructing the
      T1 and T2 vertebral bodies and compressing the spinal cord. The mass was excised
      surgically. It was follicular carcinoma metastasis of the cervicodorsal region.
      Then, she underwent a total thyroidectomy. Pathological examination showed two
      different types of carcinomas in two different focuses; follicular carcinoma in
      the left lobe and follicular variant papillary carcinoma in the isthmic lobe.
      After the operation she was given 100 mCi 131I. This is the first report of a
      patient who had both metastatic follicular carcinoma and follicular variant
      papillary carcinoma together.

PMID- 15717656
TI  - Prostatic neuroendocrine tumor in multiple endocrine neoplasia Type 2B.
AB  - We report the unusual occurrence of a neuroendocrine prostatic tumor in two young
      males with multiple endocrine neoplasia (MEN) 2B. Immunohistochemistry of the
      tumor markers may help differentiate a primary neuroendocrine prostate tumor from
      the metastasis of a medullary thyroid carcinoma of poor prognosis. MEN 2B
      hallmarks (i.e. plasma thyrocalcitonin and urinary metanephrines) may be
      systematically investigated in neuroendocrine tumors of the prostate, and
      conversely prostate examination may be performed in the periodic screening of MEN
      2B male patients.

PMID- 15717655
TI  - Does tumor heterogeneity limit the use of the Weiss criteria in the evaluation of
      adrenocortical tumors?
AB  - Adrenal incidentalomas are detected more frequently with high-resolution imaging
      modalities. It is difficult to distinguish between benign and malignant lesions
      despite the so-called histologic Weiss criteria, imaging features, and molecular
      studies. We here present a 52 yr-old man who was found to have an adrenal
      incidentaloma during an annual check-up at his urologist. An 8 cm large adrenal
      lesion was detected on ultrasound, computed tomography, and magnetic resonance
      imaging with imaging features suggestive of malignancy. The lesion was hormonally
      inactive. A left-sided adrenalectomy was performed and histologic grading
      revealed a Weiss score of 2, suggesting a benign tumor. However, on further
      follow-up, the patient developed a local recurrence and pulmonary metastases
      diagnosed 6 yr after initial presentation. After repeat surgery in the left
      adrenal bed adrenocortical tumor tissue had a Weiss score of 8, clearly
      suggesting histologic malignancy. The patient received adjuvant mitotane therapy.
      Under this therapy, he developed a right-sided adrenal mass (contralateral from
      the primary tumor) of 2 cm size which disappeared during the following 9 months,
      whereas the pulmonary metastases remained unchanged, suggesting tumor clones with
      a variable response to treatment or spontaneous apoptosis. This case suggests
      that adrenal incidentalomas larger than 6 cm with imaging features such as
      intratumoral necrosis suggestive of malignancy, should be managed as potential
      cancers independent of the so-called Weiss criteria. In such patients, close
      follow-up examinations including high-resolution imaging (preferably 3 monthly)
      are needed and should be carried out by a physician familiar/specialized in
      endocrine oncology.

PMID- 15717657
TI  - Exacerbations of Graves' disease after unilateral adrenalectomy for Cushing's
      syndrome.
AB  - Cushing's syndrome is characterized by endogenously increased production of
      glucocorticoids. The activity of immune system is regulated mainly by two systems
      in the body. Glucocorticoids and NF-kappaB counteract the effects of each other
      on the immune system. It has been reported that immune response is exaggerated
      after the amelioration of Cushing's syndrome. We report a rare case of
      exacerbation of Graves' disease after unilateral adrenalectomy for Cusing's
      syndrome. A 50-yr-obese woman with hypertension, dyslipidemia, impaired glucose
      tolerance and insulin resistance wasadmitted to outpatients clinic of
      endocrinology. The results of evaluation of glucocorticoids metabolism and
      adrenal magnetic resonance imaging revealed the Cusing's syndrome. We also
      assessed thyroid function tests because of the diagnosis of goiter and thyroid
      hormone replacement in her medical history, and the presence of exophthalmia and
      tachycardia in examination. Althoug TSH level was detected at the lower border of
      normal range, free T4 and free T3 were in normal range and autoantibody of
      thyroidal peroxidase and thyroglobulin was higer than normal reference range. An
      operation was performed and a mass was removed from her left adrenal gland. The
      pathologic examination confirmed adrenal adenoma. She was re-admitted to the
      outpatient clinic 9 months after with complaints of palpitation, malaise and
      weight loss. Tests carried out to determine the thyroid function revealed Graves'
      disease. We prescribed propylthiouracil and beta-blocker treatment.

PMID- 15717658
TI  - A novel germline mutation of MEN 1 gene in a patient with acromegaly and multiple
      endocrine tumors.
AB  - Germline mutations of the MEN 1 gene are responsible for multiple endocrine
      neoplasia type 1 (MEN 1), a dominantly inherited cancer syndrome characterized by
      tumors of the parathyroids, gastro-intestinal endocrine tissue, anterior
      pituitary and other endocrine tissues. We report on a 55-yr old woman, presenting
      with active acromegaly (due to GH-secreting microadenoma), associated to
      bilateral adrenal adenomatosis and Hurthle-cell thyroid neoplasia. No evidence of
      hyperparathyroidism or gastrin-secreting tumor was found. Peripheral blood
      genomic DNA was extracted, amplified by PCR, purified and analyzed by direct
      sequencing. The analysis revealed a heterozygous mutation in exon 4 of the MEN 1
      gene: a G to A missense mutation at codon 229 (CGC-->CAC), which changes arginine
      to histidine. This mutation causes loss of the Hhal restriction site and can thus
      be employed for a rapid familiar screening. This case represents a newly
      recognized germline mutation of the MEN 1 gene.

PMID- 15717659
TI  - Clinical manifestations and hormonal profile of two women with Cushing's disease
      and mild deficiency of 21-hydroxylase.
AB  - The development of Cushing's disease among patients with deficiency of 21
      hydroxylase has not been observed to date. The clinical manifestations and the
      hormonal profile of this exceptional association are herein described through the
      study of two cases. The first one was a 39-yr-old woman who had undergone non
      curative transsphenoidal surgery for a pituitary-dependent Cushing's syndrome 12
      yr before. She showed hypertension, central obesity, severe hirsutism, alopecia
      and hyperpigmentation. Urinary excretion of cortisol was normal, but ACTH levels
      were very high and hormonal dynamic studies (cortisol circadian rhythm, insulin
      induced hypoglycemia and dexamethasone suppression tests) revealed the
      qualitative disturbances that characterize Cushing's disease. Serum
      concentrations of androstenedione, free testosterone and 17-hydroxyprogesterone
      were clearly increased. Reexamination of the tissue samples from previous surgery
      confirmed the presence of an ACTH-producing pituitary adenoma. CYP21 gene
      analysis found the splicing 655G mutation at intron 2 and the V281L mutation at
      exon 7. The second case was a 21-yr-old woman who was diagnosed with pituitary
      ACTH-dependent Cushing's syndrome according to unequivocal clinical and
      laboratory findings. However, hirsutism was particularly severe and both serum
      androgens and 17-hydroxyprogesterone were elevated. The patient was heterozygote
      for a large conversion of CYP21 gene. In these cases, the clinical and
      biochemical expression of Cushing's syndrome was determined by the different
      severity of 21-hydroxylase deficiency and the subsequent residual ability of
      adrenal cortex to synthesize cortisol.

PMID- 15717660
TI  - Novel medical approaches for the treatment of Cushing's disease.

PMID- 15717661
TI  - Indications and strategies for continuing GH treatment during transition from
      late adolescence to early adulthood in patients with GH deficiency: the impact on
      bone mass.
AB  - GH plays an important role in longitudinal bone growth and maturation during
      childhood and adolescence. However, GH has important metabolic functions other
      than bone growth, which become more apparent during young adulthood, when growth
      has been completed. Indeed, GH deficiency (GHD) in adult life is a recognized
      clinical syndrome which includes symptoms such as increased central adiposity,
      decreased lean body mass, reduced bone mineral density (BMD), increased
      atherogenic risk, cerebrovascular and cardiac morbidity and mortality, and
      reduced quality of life. As approximately one quarter of the children with GHD
      should continue GH administration in adulthood, it is important to reconfirm GHD
      at the end of growth in order to select patients with severe GHD who need to
      resume GH therapy with an appropriate age-related dosage. Some evidence indicates
      that most peak bone mass (PBM) is achieved by the end of adolescence but small
      increases in BMD continue during the period of transition from late adolescence
      to young adulthood. Some young adults with GHD show a persistent increase of
      lumbar BMD after the completion of growth even after discontinuation of treatment
      suggesting a spontaneous progression towards lumbar PBM or a continuing effect of
      the treatment. The data indicates that adolescents with GHD who do not reach
      lumbar PBM at the time of discontinuation of GH treatment can achieve a BMD lower
      than their genetic potential if they are not treated during the transition to
      young adulthood.

PMID- 15717662
TI  - The overtraining syndrome in athletes: a stress-related disorder.
AB  - Physical exercise is a type of allostatic load for several endocrine systems,
      notably the hypothalamic-pituitary-adrenal (HPA) axis. Athletes undergoing a
      strenuous training schedule can develop a significant decrease in performance
      associated with systemic symptoms or signs: the overtraining syndrome (OTS). This
      is a stress-related condition that consists of alteration of physiological
      functions and adaptation to performance, impairment of psychological processing,
      immunological dysfunction and biochemical abnormalities. Universally agreed
      diagnostic criteria for OTS are lacking. The pituitary-adrenal response to a
      standardized exercise test is usually reduced in overtrained athletes. This HPA
      dysfunction could reflect the exhaustion stage of Selye's general adaptation
      syndrome. The most attractive hypothesis that accounts for the observed neuro
      endocrine-immune dysregulation is the Smith's cytokine hypothesis of OTS. It
      assumes that physical training can produce muscle and skeletal trauma, thus
      generating a local inflammatory reaction. With the excessive repetition of the
      training stimulus the local inflammation can generate a systemic inflammatory
      response. The main actors of these processes are the cytokines, polypeptides that
      modulate HPA function in and outside the brain at nearly every level of activity.
      It is hoped that future research will focus on endogenous risk factors for
      morbidities related to the neuro-endocrine-immune adaptation to exercise.

PMID- 15717664
TI  - Severe hyperglycemia associated with electroconvulsive therapy.

PMID- 15717663
TI  - Lanreotide autogel is a therapeutic option for patients who develop acute
      pancreatitis after somatostatin analog treatment.

PMID- 15717665
TI  - [Changes on the 2005 horizon. Interview by Marie-France Guerel].

PMID- 15717667
TI  - [Witness: experience in the field].

PMID- 15717666
TI  - [Transporting a sick child].

PMID- 15717669
TI  - House calls as a practice venture.

PMID- 15717670
TI  - Clinical assessment skills put to the test on exams.

PMID- 15717671
TI  - Productivity in dollars and cents.

PMID- 15717673
TI  - Nontraumatic pediatric surgical emergencies. A overview of select presentations.

PMID- 15717672
TI  - Patient information. Eggs: a good source of nutrition for children.

PMID- 15717674
TI  - Headaches in children and adolescents. A blueprint for pharmacologic and
      nonpharmacologic approaches.

PMID- 15717675
TI  - Weight gain concerns in the breastfed infant. Maternal factors.

PMID- 15717676
TI  - Advocating for children with ADHD. Understanding federal laws to promote
      classroom success.

PMID- 15717677
TI  - Premenstrual dysphoric disorder. A clinical trial approach to assessment.

PMID- 15717678
TI  - HIV and other STDs in older adults. Greater awareness leads to better prevention.

PMID- 15717679
TI  - It's not about the food.

PMID- 15717680
TI  - Application of natural killer T-cells to posttransplantation immunotherapy.
AB  - Graft-versus-host disease (GVHD) and graft-versus leukemia (GVL) effects are
      closely related to each other after allogeneic stem cell transplantation. This
      association exists because of the extensive and complicated interaction between
      cellular donor components and recipient components concomitant with cytokine
      storms. It has been demonstrated that part of this interaction may be related to
      the induction of a variety of regulatory cells, such as regulatory T-cells and
      natural killer T (NKT) cells. A lower number of NKT cells may be found in
      patients with autoimmune diseases, cancer, viral infection, and severe GVHD. When
      activated, NKT cells rapidly release suppressive cytokines, such as interleukin 4
      (IL-4), IL-10, and IL-13, as well as inflammatory cytokines, such as interferon
      gamma and tumor necrosis factor alpha. NKT cells therefore act as a double-edged
      sword in their progressive or suppressive effects on diseases. Such contradictory
      phenomena may be related to the function or types of antigen-presenting cells
      (APCs) in response to their ligand. A single-dose injection of a ligand for NKT
      cells, alpha-galactosylceramide (alpha-GalCer), can induce immunity through fully
      mature dendritic cells in an antigen-specific manner. By contrast, multiple
      injections of alpha-GalCer would induce tolerance, which may be caused by
      immature APCs. This response suggests that the function of NKT cells can be
      determined by alpha-GalCer for controlling the immune response. Furthermore,
      activation of NKT cells followed by activation of APCs and IL-12 production may
      lead to activation of NK cells and suppress GVHD in mismatched major
      histocompatibility complex combinations or may induce GVL effects. Control and
      modification of NKT cell function may play an important role in regulating
      GVHD/GVL effects.

PMID- 15717681
TI  - Potential role of natural killer cell receptor-expressing cells in immunotherapy
      for leukemia.
AB  - Natural killer cell receptor (NKR)-expressing cells have cytolytic activity
      against leukemic cells, and solid tumor cells escape from T-cell recognition
      because of the low expression levels of class I HLA molecules in both allogeneic
      and autologous settings. This characteristic feature of NK cell recognition of
      target cells in contrast with that of T-cells provides a strategy to overcome
      tolerance in the tumor-bearing host. Furthermore, inhibitory NKR-expressing cells
      may have cytolytic activity and immunoregulatory functions. Several methods can
      be used to expand NKR-expressing cells for adoptive immunotherapy for leukemia
      and other malignant diseases. We review recent developments in the biology and
      clinical application of NKR-expressing cells, such as NK cells, lymphokine
      activated killer cells, cytokine-induced killer cells, NKT cells, and other NKR
      expressing cells.

PMID- 15717682
TI  - Natural killer cell alloreactivity in haploidentical hematopoietic stem cell
      transplantation.
AB  - Natural killer (NK) cells are primed to kill by several activating receptors. NK
      cell killing of autologous cells is prevented because NK cells coexpress
      inhibitory receptors (killer cell immunoglobulin-like receptors [KIR]) that
      recognize groups of (self) major histocompatibility complex class I alleles.
      Because KIRs are clonally distributed, the NK cell population in any individual
      are constituted of a repertoire with a variety of class I specificities. NK cells
      in the repertoire mediate alloreactions when the allogeneic targets do not
      express the class I alleles that block them. After haploidentical hematopoietic
      transplantation, NK cell-mediated donor-versus-recipient alloresponses reduce the
      risk of relapse in acute myeloid leukemia patients while improving engraftment
      and protecting against graft-versus-host disease. High-resolution molecular HLA
      typing of recipient and donor, positive identification of donor KIR genes, and,
      in some cases, functional assessment of donor NK clones identify haploidentical
      donors who are able to mount donor-versus-recipient NK alloreactions.

PMID- 15717683
TI  - Expansion of CD34+ cells on telomerized human stromal cells without losing
      erythroid-differentiation potential in a serum-free condition.
AB  - Erythropoiesis progresses from stem cell expansion on stromal cells through the
      formation of an erythroblastic island. Our aim was to assess the feasibility of
      using human stromal cells for erythroid production and differentiation. When cord
      blood CD34+ cells were cocultured with telomerized human stromal cells (hTERT
      stromal cells) for 2 weeks, the CD34+ cells and burst-forming units-erythroid
      (BFU-E) significantly expanded, and a few hematopoietic cells transmigrated below
      the stromal layer. When nonadherent hematopoietic progenitor cells that had
      expanded above the hTERT-stromal cells (group B) were collected and subjected to
      our erythroid-differentiation protocol, they differentiated into erythroblasts
      with a slight hemoglobin synthesis. When the few hematopoietic cells that had
      transmigrated below the stromal layer were expanded for an additional 2 to 6
      weeks, they exhibited a cobblestone-like appearance, and a large amount of BFU-E
      clambered weekly from the underside of the stromal layer to above the stromal
      layer (group C). When the hematopoietic progenitor cells in group C were
      subjected to the erythroid-differentiation protocol, large numbers of mature
      erythroblasts (more than 300,000 times the initial CD34+ cell number) were
      produced. Our hTERT-stromal expansion protocol may contribute to the construction
      of a system for large-scale, long-term production of erythroid cells.

PMID- 15717685
TI  - CD2+ tetraploid acute promyelocytic leukemia variant with double (15;17)
      translocations.
AB  - We report a patient with a variant form of CD2+ acute promyelocytic leukemia
      (APL) who had double translocations (15;17) in a single leukemic cell. The
      patient presented with severe neutropenia, thrombocytopenia, and disseminated
      intravascular coagulation. The bone marrow showed marked hyperplasia with large
      leukemic cells that had bizarre nuclear configuration and basophilic,
      hypogranular cytoplasm. Leukemic cells were positive for CD2, 13, 33, 34, and 56
      and negative for HLA-DR. The karyotype of the abnormal clone was characterized as
      92,XXYY, t(15;17)(q22;q21)x2. No other additional abnormal clone was found, and
      the patient's condition was diagnosed as tetraploid APL variant. Fluorescence in
      situ hybridization assay revealed 2 promyelocytic leukemia and retinoic acid
      receptor alpha (PML/RARA) fusion signals, and reverse transcription-polymerase
      chain reaction assay revealed short-form PML/RARA fusion transcript. Tetraploidy
      in APL is a very rare abnormality. Double translocations were an additional
      abnormality in this case, and this patient's karyotype might have had some
      influence on morphological characteristics, expression of CD2, and poor clinical
      outcome.

PMID- 15717684
TI  - Familial Mediterranean fever and E148Q pyrin gene mutation in Greece.
AB  - Familial Mediterranean fever (FMF) is an inherited disease characterized by
      recurrent inflammatory polyserositis. Although FMF is classically expected only
      in Middle East populations, it is becoming evident that the disease affects more
      groups than initially thought. The disease is associated with a number of
      mutations of the MEFV gene, which codes for a protein named pyrin. The role of
      E148Q pyrin gene mutation in the development of FMF remains inconclusive. Some
      authors believe it causes the disease, whereas others favor the concept of a
      noncausative role. To understand better the role of this mutation, gathering data
      from different populations may be of value. We studied 60 Greek cases fulfilling
      the criteria for FMF diagnosis, 30 cases being a definite FMF diagnosis and 30 a
      probable diagnosis. Twenty-one of the patients, carried mutation E148Q. One was a
      homozygote (E148Q/E148Q), and 20 carried mutation E148Q in combination with other
      mutations (compound heterozygotes). In 6 of the 60 cases studied, no mutations
      were found. Compared with the results for healthy controls, E148Q mutation is
      significantly frequent. Because different populations may exhibit different
      patterns of pyrin mutations, association of the E148Q mutation with FMF should be
      considered in connection with origin data.

PMID- 15717686
TI  - Synergistic effects of dehydroepiandrosterone and retinoic acid on granulocytic
      differentiation of human promyelocytic NB4 cells.
AB  - We report a novel effect of dehydroepiandrosterone (DHEA) on human granulocyte
      differentiation: DHEA enhances the all-trans-retinoic acid (ATRA)-induced
      differentiation of promyelocytic NB4 cells. DHEA (100 microM) significantly
      augmented the respiratory burst activity of NB4 cells treated with 1 nM ATRA,
      whereas DHEA alone did not induce respiratory burst activity. The protein and
      message expressions of p67phox, the gene for the dose-limiting component of
      phagocyte NADPH oxidase, were significantly enhanced by the coexistence of DHEA
      and ATRA. The protein expression of p47phox, another component of phagocyte NADPH
      oxidase, was also up-regulated by DHEA and ATRA. Moreover, the ATRA-induced
      increment of CCAAT/enhancer-binding protein beta (C/EBPbeta) and the reciprocal
      reduction in C/EBPUalpha expression were also potentiated by DHEA. In contrast,
      the expression of PU.1, a transcription factor reportedly involved in the basal
      expression of p67phox in monocytic cells, was only slightly up-regulated by DHEA
      and ATRA. Interestingly, DHEA sulfate (DHEAS), the sulfate ester of DHEA that
      exists in peripheral blood at a concentration approximately 3 orders of magnitude
      larger than that of DHEA, did not stimulate the ATRA-induced differentiation of
      NB4 cells. Thus, DHEA, but not DHEAS, plays important roles in synergy with ATRA
      during granulocyte differentiation of human promyelocytic NB4 cells.

PMID- 15717687
TI  - GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute
      lymphoblastic leukemia.
AB  - The probability of event-free survival of childhood acute lymphoblastic leukemia
      (ALL) approaches 80% or more with the use of modern multiagent chemotherapeutic
      regimens. One major contribution to this success has been reduction of the rate
      of central nervous system (CNS) relapses to less than 5%. However, heterogeneity
      is observed with regard to the incidence of CNS relapse in homogenously treated
      patient populations. One potential explanation for this heterogeneity is
      variation in the genetic background of these populations. Glutathione S
      transferase P1 and P-glycoprotein are implicated in resistance to a variety of
      chemotherapeutic agents and have been localized to the blood-brain barrier. In a
      matched case-control study, we investigated the associations between CNS relapse
      in childhood ALL and the presence of phenotypically relevant single nucleotide
      polymorphisms within the GSTP1 (codon 105 and 114) and MDR1 genes (ABCB1; coding
      for Pgp; exon 26, C3435T). Significant reductions in risk of CNS relapse were
      observed for patients homozygous for the GSTP1 Val105 allele as well as for
      patients with the MDR1 3435T/T or C/T genotype. For both genotypes, the effect
      was restricted to patients at intermediate or high risk of treatment failure.
      These results suggested a modulating role for host genetic variation in the
      development of CNS relapse in childhood ALL treated according to Berlin-Frankfurt
      Munster protocols.

PMID- 15717688
TI  - Marked reduction of LL-37/hCAP-18, an antimicrobial peptide, in patients with
      acute myeloid leukemia.
AB  - We detected LL-37/hCAP-18 expression in the peripheral blood smears of 50 healthy
      donors and 143 patients with various hematological diseases. Compared with that
      in the healthy donors, expression of the protein in the neutrophils was
      significantly lower in patients with acute myeloid leukemia (AML), especially
      those with infection, but no significant difference was detected in messenger RNA
      level. We did not detect increased LL-37/hCAP-18 protein expression in U937 cells
      treated with lipopolysaccharide or Staphylococcus aureus Cowan strain.
      Furthermore, LL-37/hCAP-18 protein production was not restored in differentiated
      myeloid cell lines NB4 or HL-60 induced by all-trans retinoic acid. LL-37/hCAP-18
      has been shown to play a role in host defense, and its deficiency in AML may be
      one of the explanations for susceptibility to infection among these patients.

PMID- 15717689
TI  - Incidence of diffuse large B-cell lymphoma of germinal center B-cell origin in
      whole diffuse large B-cell lymphoma: tissue fluorescence in situ hybridization
      using t(14;18) compared with immunohistochemistry.
AB  - Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically
      important categories such as germinal center B (GCB)-like and non-GCB-like
      groups. The t(14;18)(q32;q21) translocation defines a unique subset of DLBCL
      cases with a GCB gene expression profile. Two-color fluorescence in situ
      hybridization (FISH) analysis was applied to detect t(14;18) (q32;q21) in the
      nuclei of paraffin-embedded tissue sections from 61 patients with de novo DLBCL.
      Nine (15%) of 61 cases had a positive pattern. Fifty-seven cases were
      subclassified in an immunohistochemical study with anti-CD10, anti-bcl-6, and
      anti-MUM1 antibodies. In this classification, 21 cases (37%) were placed in the
      GCB group, and 36 (63%) were placed in the non-GCB group. There was a discrepancy
      between t(14;18) occurrence and bcl-2 protein expression. Bcl-2 protein
      expression was positive in 40 (67%) of 60 cases. The expression of bcl-2 protein
      in the GCB and non-GCB groups was not significantly different: 15 (71%) of 21
      cases in the GCB group and 24 (67%) of 36 cases in the non-GCB group tested
      positive. We found no difference between the FISH-positive and FISH-negative
      groups in overall survival time (P = .6019, log-rank test). The overall survival
      rates of GCB and non-GCB groups did not differ significantly by
      immunohistochemical classification (P = .5399, log-rank test). Overall survival
      was significantly longer in the group with a low International Prognostic Index
      (IPI) score than in the group with a high IPI score (P = .0002, log-rank test).
      Our results suggest that immunohistochemical study and cytogenetic study with
      t(14;18) FISH cannot predict the clinical outcomes of DLBCL patients. A study
      with a larger number of patients may show a difference in clinical outcomes
      between FISH-positive and FISH-negative groups and between GCB and non-GCB
      groups.

PMID- 15717690
TI  - CD5+ diffuse large B-cell lymphoma consists of germline cases and hypermutated
      cases in the immunoglobulin heavy chain gene variable region.
AB  - CD5+ diffuse large B-cell lymphoma (DLBCL) has recently been identified as a
      subgroup with different clinical characteristics from CD5- DLBCL and as having a
      poorer outcome than CD5- DLBCL. Data regarding differences in gene alteration
      between CD5+ and CD5- DLBCL have accumulated. In this article, we report an
      analysis of the immunoglobulin heavy-chain gene variable region (VH) gene in 35
      cases of CD5+ DLBCL and compare these cases with those with the germline of the
      VH gene (GL-VH) and those with a somatically hypermutated VH gene (HM-VH). When
      the CD5+ DLBCL cases were subdivided with a cutoff value of 98% homology in the
      VH gene, there were 7 cases (20%) of GL-VH and 28 cases (80%) of HM-VH. The
      proportion of GL-VH cases in CD5+ DLBCL was more than that in CD5 DLBCL. Although
      we found no significant difference in pretreatment clinical parameters between
      the GL-VH and HM-VH subgroups, there was a tendency for the GL-VH subgroup to
      show lower incidences of elevation of lactate dehydrogenase and >1 site of
      extranodal involvement compared to the HM-VH subgroup. The overall survival curve
      of the HM-VH subgroup showed a rapid decline followed by a plateau, whereas that
      of the GL-VH subgroup declined constantly after 5 years, suggesting that GL-VH
      disease may not be curable by standard therapies. These findings suggest that
      CD5+ DLBCL with GL-VH shares clinical features with mantle cell lymphoma, the
      cellular origin of which has been considered to be pre-germinal center B-cells.
      We therefore propose that analysis of the VH gene is important for predicting the
      clinical course of CD5+ DLBCL.

PMID- 15717691
TI  - Polyclonal proliferation of plasma cells associated with marked
      hypergammaglobulinemia in an elderly patient.
AB  - We describe an 89-year-old woman who presented with prominent plasmacytosis
      mimicking plasma cell leukemia. The apparent serum M-protein level of > 7 g/dL of
      gamma mobility was revealed to be a polyclonal increase of immunoglobulins. The
      plasma cells in the peripheral blood expressed polyclonal surface/cytoplasmic
      immunoglobulins as well as CD19, CD30, CD38, and CD138 antigens but lacked CD10,
      CD20, CD25, and CD56. The bone marrow plasma cells showed the CD45+, CD19+, CD56
      , MPC-1(-/+), and CD49e- immunophenotype, which was in clear contrast with the
      immunophenotypes of the neoplastic myeloma cells. Abdominal lymphadenopathy,
      splenomegaly, and a high level of soluble interleukin 2 receptor may have been
      reflections of an underlying lymphoproliferative disorder, potentially leading to
      the polyclonal proliferation of plasma cells.

PMID- 15717692
TI  - Small cell variant of T-cell prolymphocytic leukemia with a gammadelta
      immunophenotype.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a rare postthymic T-cell disorder. The
      disease is characterized by lymphadenopathy, splenomegaly, skin lesions, a high
      white blood cell count, and an aggressive clinical course. The small cell variant
      of T-PLL occurs in approximately 20% of patients. Most T-PLL patients express
      membrane T-cell receptors (TCR) of the alphabeta phenotype. The diagnosis of
      small cell variant T-PLL in a 56-year-old woman was based on the findings of
      abnormal lymphocytosis, immunophenotype, lymphadenopathy, and aggressive clinical
      behavior. Immunophenotype analysis showed that lymphocytes were positive for CD2,
      CD3, CD5, CD7, CD8, and TCR gammadelta antigens and negative for CD1a, CD4, and
      TCR alphabeta antigens. Southern blot analysis revealed rearrangement of the TCR
      Jgamma and Jdelta-1 genes. A cytogenetic study of peripheral blood showed a
      normal karyotype. T-PLL with a TCR gammadelta phenotype is very rare. This case
      was typical T-PLL except for the morphologically small cell type and the lack of
      the typical chromosome aberration. If cases accumulate in the future, the
      specific features of the gamma8 type of T-PLL will become clearer.

PMID- 15717693
TI  - Risk-adapted preemptive therapy for cytomegalovirus disease after allogeneic stem
      cell transplantation: a single-center experience in Korea.
AB  - Cytomegalovirus (CMV) remains a major cause of infection in recipients of
      hematopoietic stem cell transplants (HSCT) and results in significant mortality
      and morbidity. We present the results of CMV pp65 antigenemia-guided, risk
      adapted preemptive therapy aimed at preventing CMV disease in allogeneic HSCT.
      Preemptive ganciclovir treatment was started when more than 5 CMV antigen
      positive cells were detected in the low-risk group (with grade 0-I acute GVHD and
      matched related HSCT) and when any antigen-positive cells were seen in the high
      risk group (with grade II-IV acute GVHD or matched unrelated HSCT). At least 1
      episode of antigenemia was observed in 53 (59.6%) of 89 patients before day 100,
      and preemptive therapy was performed in 33 patients. CMV disease occurred in 6
      patients (5 in the high-risk group and 1 in the low-risk group), and late CMV
      disease developed in 4 patients. Only 1 patient died of CMV pneumonitis before
      day 100. Neutropenia was observed in 51.5% of ganciclovir-treated patients, and
      coinfection/superinfection was observed in 42.4%. A strategy of ganciclovir
      treatment focusing on patients at higher risk could reduce the toxicity from the
      antiviral drug and be cost-effective. Extended surveillance for CMV disease using
      more sensitive diagnostic methods is necessary in high-risk patients.

PMID- 15717694
TI  - Recombinant factor VIIa is an effective therapy for abdominal surgery and severe
      thrombocytopenia: a case report.
AB  - A 50-year-old woman was admitted to the emergency room. An appendectomy was done.
      On the sixth day the patient's general state deteriorated and she became
      somnolent with jaundice due to distal obstructive choledocholithiasis. The
      results of laboratory tests were platelets 12 x 10(9)/L, prothrombin time 13
      seconds, international normalized ratio 1.19, activated partial thromboplastin
      time 31.8 seconds, and fibrinogen 8.78 g/L. There was no evidence of disseminated
      intravascular coagulation. In view of the patient's clinical condition, surgery
      was considered to be indicated. Because it was a life-threatening situation and
      at the time there was no platelet concentrate available for immediate
      transfusion, she was treated with a single dose of recombinant factor VIIa
      (rFVIIa) (60 microg/kg). The dose of 60 microg/kg was selected on the basis of
      experience with rFVIIa in the treatment of hemophilic patients. In this case, use
      of rFVIIa was a valid alternative to control the bleeding in a patient with
      thrombocytopenia. However, despite the efficacy of the treatment, it should not
      be forgotten that it was used because of the unavailability of platelets and that
      we were dealing with a life-threatening situation. Clinical trials should be
      carried out to verify the safety, effectiveness, and efficiency of rFVIIa in
      these cases.

PMID- 15717696
TI  - Fludarabine-based conditioning used in successful bone marrow transplantation
      from an unrelated donor in a heavily transfused patient with severe aplastic
      anemia.

PMID- 15717695
TI  - Glanzmann thrombasthenia with acute myeloid leukemia successfully treated by bone
      marrow transplantation.
AB  - We report successful treatment by bone marrow transplantation (BMT) in an acute
      myeloid leukemia (AML) patient with Glanzmann thrombasthenia (GT). Genetic
      analysis revealed that a novel point mutation in exon 3 of the GPIIb gene led to
      abnormal splicing resulting in an amino acid substitution and an in-frame
      deletion of 3 amino acid residues. Expression studies suggested a rapid
      degradation of the uncomplexed protein within the cells. Induction therapy for
      AML was performed with frequent platelet transfusions because of the patient's
      severe hemorrhagic manifestations. In the second remission, the patient was
      successfully treated by BMT from an HLA-matched unrelated donor. Platelet
      function returned to normal, and the GT phenotype completely disappeared. Our
      experience suggests that BMT is a curative therapeutic strategy for GT.
      Furthermore, we believe this study is the first to demonstrate that engraftment
      after BMT for AML can be determined by monitoring the congenital genetic defect
      of GT.

PMID- 15717697
TI  - Recent advances in local anaesthetics for spinal anaesthesia.
AB  - Although local anaesthesia is mentioned in historical manuscripts, it is only a
      hundred years since Bier first reported the intrathecal use of local anaesthetic
      agents. This has been followed by a rapid progression in the art and science of
      spinal anaesthesia. Isomerically pure agents with favorable clinical profiles,
      such as ropivacaine and levobupivacaine are now available. Spinal anaesthesia is
      commonly used in a variety of situations, including orthopaedic, abdominal,
      gynaecological surgery, Caesarean section and the relief of pain in childbirth.
      Hyperbaric solutions of local anaesthetics appear to produce more consistent
      results than plain solutions and the addition of other drugs, such as opioids and
      clonidine may improve analgesia. In addition to traditional spinal anaesthesia,
      local anaesthetics are now being evaluated in continuous spinal anaesthesia and
      combined epidural-spinal anaesthesia. This article reviews clinical experience
      with levobupivacaine and ropivacaine. Compared with levobupivacaine, ropivacaine
      generally produces a less intense motor block of shorter duration, which has
      advantages for earlier mobilization and discharge from hospital and may be
      particularly useful in obstetrics and ambulatory surgery.

PMID- 15717699
TI  - Combined epidural/spinal anaesthesia: needle-through-needle or separate spaces?
AB  - BACKGROUND AND OBJECTIVE: This prospective, randomized and blinded study compared
      the performance of a new needle-through-needle (NTN) kit (Epistar; Medimex,
      Germany) with the double-space technique for providing combined spinal epidural
      anaesthesia during Caesarean section. METHODS: Following local Ethics Committee
      approval and patient consent, 200 females were randomized to receive combined
      spinal epidural anaesthesia by the double-space (n = 100) or NTN (n = 100)
      technique. The frequency with which the intrathecal component could achieve a T5
      block to touch for Caesarean section without the need for epidural augmentation
      or an alternative technique was determined. The time from start of procedure to
      achieving a block height to T5 was recorded. Pain and backache at insertion, and
      at 24 h follow-up were recorded using a visual analogue scale. To remove any bias
      due to posture, 50% of each group were further randomized to receive their block
      in the sitting or in the left lateral position. To evaluate improvement of
      performance over time the success in the first 100 study patients were compared
      to the success in the second 100. RESULTS: A successful block to T5 with the
      double-space and NTN techniques were 80 vs. 54, odds ratio 0.29. Failure to enter
      the intrathecal space once the epidural space had been located occurred in 29
      patients in the NTN group. Time to readiness for surgery was 15 min (95%
      confidence interval (CI): 12.7-17.4) and 12.9 min (95% CI: 11.5-14.3) for the
      double-space and NTN techniques, respectively. The median (interquartile range)
      visual analogue scores for discomfort at insertion were 30 (12.5-51.5) and 32
      (12.75-60) and for postoperative backache 0 (0-10) and 0 (0-10.75) in the double
      space and NTN groups, respectively. The number of epidural augmentations was
      similar in both the groups and posture made no difference. There was a tendency
      to increased success in the second half of the study. CONCLUSION: The double
      space technique had a greater success rate than the NTN technique.

PMID- 15717700
TI  - Influence of microcatheter length on flow rates of disposable infusion kits.
AB  - BACKGROUND AND OBJECTIVE: Continuous spinal analgesia (CSA) offers considerable
      pain relief, and has been used in various procedures such as for surgery and
      cancer pain control. In Japan, portable and disposable infusion kits are
      increasingly employed for continuous epidural analgesia and CSA. In CSA, the use
      of a microcatheter is expected to reduce the incidence of spinal headache
      previously encountered with larger catheters. However, the flow rate of
      disposable infusion kits is reduced when used in conjunction with a
      microcatheter. METHODS: This study aimed to investigate the influence of catheter
      length on the flow rate of two different devices: 20- or 91-cm 28-G
      microcatheters connected to balloon- or syringe-type infusion pumps were examined
      (50 mL, 1 mL h(-1)). There were four groups each of 10 experiments: Group A:
      balloon-type infuser, 91 cm catheter; Group B: balloon-type infuser, 20 cm
      catheter; Group C: syringe-type infuser, 91 cm catheter; Group D: syringe-type
      infuser, 20 cm catheter. RESULTS: The mean flow rate in Group A was significantly
      less than that in Group B and the mean flow rate in Group C was significantly
      less than Group D (P < 0.05). CONCLUSION: These results indicated that the use of
      a shorter microcatheter achieves a better flow rate during CSA.

PMID- 15717698
TI  - Influence of underlying disease on the outcome of critically ill patients with
      acute renal failure.
AB  - BACKGROUND AND OBJECTIVE: The development of acute renal failure (ARF) in
      critically ill patients is associated with an increase in hospital mortality.
      Recently, it was shown that starting renal replacement therapy early and using
      high-filtrate flow rates can improve the outcome, but this could not be confirmed
      in later investigations. Studying selected patient subgroups could provide a
      useful basis for patient selection in future trials evaluating the outcome of
      renal replacement therapies. We, therefore, investigated the impact of the
      underlying disease on the outcome of patients with ARF. METHODS: We
      retrospectively analysed 306 patients with ARF who were treated with renal
      replacement therapy. Patients were classified according to six initial diagnosis
      groups: haemorrhagic shock, post-cardiac surgery, post-liver transplantation,
      trauma, severe sepsis and miscellaneous. Univariate and multivariate multiple
      logistic regression analysis was used to determine which factors influenced the
      outcome. RESULTS: Underlying disease proved to be the only independent risk
      factor for mortality that was present at intensive care unit (ICU) admission (P =
      0.047). Patients with severe sepsis had a significantly higher mortality rate
      (68%) than ARF patients as a whole (51%) (P = 0.02). Length of stay in the ICU,
      the use of catecholamines, the delay before ARF onset, and the correlation
      between APACHE II score and ICU length of stay proved to be additional
      independent predictors of outcome. CONCLUSIONS: Patient selection and subgroup
      definition according to the underlying disease could augment the usefulness of
      future trials evaluating the outcome of ARF.

PMID- 15717701
TI  - Difficult airway equipment in obstetric units in the republic of Ireland: results
      of a national survey.
AB  - BACKGROUND AND OBJECTIVE: Difficult intubation in obstetric units has been
      identified as a major contributory factor to anaesthesia related maternal
      morbidity and mortality. Availability of equipment for management of a difficult
      airway is associated with reduced maternal complications. The purpose of our
      survey was to describe the availability of difficult airway equipment in Irish
      Obstetric Units. METHODS: A telephone survey was conducted in which all
      respondents were asked whether they housed basic airway equipment, alternative
      ventilation and alternative intubation equipment within or close to their
      obstetric unit. RESULTS: The most important finding of this study is that all the
      obstetric units in Ireland hold at least one alternative device for both
      ventilation and intubation. The most common alternative ventilation device was
      the laryngeal mask airway and the most common alternative intubating device was
      the surgical airway device. CONCLUSIONS: Irish Obstetric Units are well equipped
      according to the international guidelines for difficult intubation equipment.
      However, we believe that this situation could be further improved by training
      inexperienced anaesthetists in the use of the Intubating Laryngeal Mask and by
      the increased use of portable trolleys.

PMID- 15717702
TI  - Epidural anaesthesia with bupivacaine does not cause increased oedema in small
      gut anatomoses in pigs.
AB  - BACKGROUND AND OBJECTIVE: Epidural analgesia is widely used for abdominal surgery
      due to the properties of 'stress-free' anaesthesia and superior pain control.
      Nevertheless, sympathomimetics are known to antagonize inflammation. The present
      study was performed to investigate if epidural local anaesthetics caused
      increased local oedema formation. METHODS: Thirty Dansk Landrace pigs were
      randomized into three groups: epidural bupivacaine, epidural morphine or
      intravenous (i.v.) fentanyl. All animals were anaesthetized with isoflurane and
      i.v. midazolam and received an identical fluid regimen. Six small bowel
      resections were performed over a 3-h period and during the following 3 h the
      anastomoses were resected. Primary end-points were water content in small bowel
      and mesentery samples before and after gut anastomosis, lymph flow and urine
      production. RESULTS: The water content in the small bowel samples was not changed
      by surgery or by the different anaesthetic protocols. In the mesenteric tissue,
      there was a highly significant increase in water content of the postanastomotic
      samples compared to pre-anastomotic samples (P < 0.001) and a significant time
      treatment interaction was revealed (P < 0.05) suggesting an increase in oedema
      formation in the epidural local anaesthetic group. Lymph flow did not change
      during the experiments and there were no significant differences between the
      groups (P = 0.80). The mean total urine output was 44% higher in the epidural
      morphine group compared to the local anaesthetic group (P = 0.17). CONCLUSIONS:
      Surgery did not increase gut wall water content, but acute oedema formation
      resulted in the peri-resectional mesenterial tissue, more prominently so in the
      bupivacaine group.

PMID- 15717703
TI  - Midazolam attenuates adenosine diphosphate-induced P-selectin expression and
      platelet-leucocyte aggregation.
AB  - BACKGROUND AND OBJECTIVE: The expression of P-selectin on the surface of
      platelets and platelet-leucocyte conjugate formation are considered to be an
      indicator of platelet activation in thrombotic and inflammatory disease.
      Midazolam is a widely used sedative and anaesthetic induction agent. It may
      inhibit platelet aggregation and suppress interleukin-6 and -8 response in human
      leucocytes, but any effect on the adhesion of activated platelets to leucocytes
      remains obscure. We have examined the influence of midazolam on adenosine
      diphosphate (ADP)-induced platelet surface P-selectin expression and platelet
      leucocyte aggregation in whole blood. METHODS: Human whole blood was stimulated
      with 2 x 10(-5)M ADP in the presence of midazolam (3 x 10(-4) to 3 x 10(-6)M).
      Samples were stained with a fluorochrome-conjugated CD62P and CD41a antibody for
      detecting human platelet P-selectin antigens. The leucocyte subpopulations were
      separately gated and platelet-leucocyte aggregates were defined as cells found
      positive for CD45 and CD62P. All samples were analysed and were electronically
      separated into specific cell types (platelets, neutrophils, monocytes and
      lymphocytes) according to their typical forward/side scattering by flow
      cytometry. RESULTS: Midazolam significantly inhibited ADP-induced platelet P
      selectin expression and attenuated platelet-leucocyte aggregation (mainly in
      neutrophils and monocytes) in a dose-dependent manner with a maximum inhibitory
      effect at 3 x 10(-4)M (P < 0.01). CONCLUSIONS: This study demonstrated that
      midazolam decreases the ADP-induced expression of platelet surface P-selectin and
      platelet-leucocyte aggregation.

PMID- 15717704
TI  - Assessment of neuromuscular and haemodynamic effects of cisatracurium and
      vecuronium under sevoflurane-remifentanil anaesthesia in elderly patients.
AB  - BACKGROUND AND OBJECTIVE: Neuromuscular block times, quality of muscle relaxation
      for tracheal tube insertion, and the haemodynamic effects after cisatracurium and
      vecuronium under sevoflurane-remifentanil anaesthesia were compared in elderly
      patients. METHODS: The study was performed in 40 patients over 65 yr of age.
      Anaesthesia was induced with thiopental, and maintained with sevoflurane in
      N2O/O2 and remifentanil. Cisatracurium 0.15 mg kg(-1) or vecuronium 0.1 mg kg(-1)
      were administered after induction. Intubation was attempted when neuromuscular
      block was 95%. Onset time, clinical duration of action, recovery index,
      spontaneous recovery time and tracheal intubation conditions were assessed.
      Haemodynamic parameters were also monitored. RESULTS: The average ages of the
      patients were 72.5 +/- 5.1 and 73.6 +/- 6.3 in the cisatracurium and vecuronium
      groups, respectively. Onset time was significantly shorter after vecuronium, 158
      +/- 34 s vs. 200 +/- 50s, respectively. Recovery index was significantly shorter
      after cisatracurium, 19.5 +/- 7.5 s vs. 33.7 +/- 18.6 s (P < 0.05). Clinical
      duration and spontaneous recovery time were similar in both groups as well as
      haemodynamic variables. CONCLUSIONS: In elderly patients, vecuronium has a faster
      onset time while cisatracurium has a shorter recovery index under sevoflurane
      remifentanil anaesthesia.

PMID- 15717705
TI  - An interstitial compartment is necessary to link the pharmacokinetics and
      pharmacodynamics of mivacurium.
AB  - BACKGROUND AND OBJECTIVE: The time course of action of mivacurium does not
      correlate with its rapid breakdown by plasma cholinesterase. Pharmacokinetic
      pharmacodynamic (PK-PD) modelling was applied to obtain more insight in the
      concentration-effect relationship. METHODS: Fourteen patients between 25 and
      55yr, undergoing non-major surgery, American Society of Anesthesiologists Grade I
      II, were included. All patients received
      thiopentone/fentanyl/isoflurane/oxygen/nitrous oxide anaesthesia. Neuromuscular
      block was monitored mechanomyographically using single twitch stimulation (0.1
      Hz). Mivacurium was administered as a short-term infusion, mean (standard
      deviation) duration 4.7 (1.0) min and dose 145 (33) microg kg(-1). Arterial blood
      samples were obtained, and plasma was analysed using high performance liquid
      chromatography. PK-PD modelling was performed using an iterative Bayesian two
      stage approach, assuming that the trans-trans and cis-trans isomers are equally
      potent. RESULTS: A PK-PD model with an effect compartment linked to plasma did
      not fit to the data satisfactorily. A model using an interstitial space
      compartment between plasma and effect compartment fitted significantly better.
      Parameters (mean (percentage coefficient of variation)) of the best fitting model
      were: k(ip) 0.374 min(-1) (46%), k(ei) 0.151 min(-1) (36%), EC50 98 microg L(-1)
      (29%) and gamma 3.7 (22%). CONCLUSIONS: The PK-PD behaviour of mivacurium could
      be described using a model with an interstitial space compartment interposed
      between plasma and effect compartment. This model shows that the time course of
      mivacurium is mainly governed by the concentration decline in this interposed
      compartment and only indirectly related to the rapid plasma clearance.

PMID- 15717706
TI  - The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule
      expression induced by plasma obtained during tourniquet-induced ischaemia and
      reperfusion.
AB  - BACKGROUND: Changes in neutrophil and endothelial adhesion molecule expression
      occur during perioperative ischaemia and reperfusion (I/R) injury. We
      investigated the effects of lidocaine on neutrophil-independent changes in
      neutrophil and endothelial adhesion molecule expression associated with
      tourniquet-induced I/R. METHODS: Plasma was obtained from venous blood samples
      (tourniquet arm) taken before (baseline), during, 15 min, 2 and 24 h following
      tourniquet release in seven patients undergoing elective upper limb surgery with
      tourniquet application. Isolated neutrophils from healthy volunteers (n = 7) were
      pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)
      for 1 h, and then incubated with I/R plasma for 2 h. Human umbilical vein
      endothelial cells (HUVECs) were pretreated in the presence or absence of
      lidocaine (0.005, 0.05 and 0.5 mg mL(-1)) for 1 h, and then incubated with the
      plasma for 4 h. Adhesion molecule expression was estimated using flow cytometry.
      Data were analysed using ANOVA and post hoc Student-Newman-Keuls tests. RESULTS:
      I/R plasma (withdrawn 15 min following tourniquet release) increased isolated
      neutrophil CD11b (P = 0.03), CD18 (P = 0.01) and endothelial intercellular
      adhesion molecule-1 (ICAM-1) (P = 0.008) expression compared to baseline. CD11b,
      CD18 and ICAM-1 expression on lidocaine (0.005 mg mL(-1)) treated neutrophils was
      similar to control. CD11b (P < 0.001), CD18 (P = 0.03) and ICAM-1 (P = 0.002)
      expression on lidocaine (0.05 mg mL(-1)) treated neutrophils and HUVECs was less
      than that on controls. CONCLUSION: Increased in vitro neutrophil and endothelial
      cell adhesion molecule expression on exposure to plasma obtained during the early
      reperfusion phase is diminished by lidocaine at greater than clinically relevant
      plasma concentrations.

PMID- 15717707
TI  - Anaesthesiologists' views on the need for point-of-care information system in the
      operating room: a survey of the European Society of Anaesthesiologists.
AB  - BACKGROUND AND OBJECTIVE: In this preliminary study we wanted to explore the
      attitudes of anaesthesiologists to a point-of-care information system in the
      operating room. The study was conducted as a preliminary step in the process of
      developing such a system by the European Society of Anaesthesiologists (ESA).
      METHODS: A questionnaire was distributed to all 2240 attendees of the ESA's
      annual meeting in Gothenburg, Sweden, which took place in April 2001. RESULTS: Of
      the 329 responders (response rate of 14.6%), 79% were qualified specialists with
      more than 10 yr of experience (68%), mostly from Western Europe. Most responders
      admitted to regularly experiencing lack of medical knowledge relating to real
      time patient care at least once a month (74%) or at least once a week (46%), and
      39% admitted to having made errors during anaesthesia due to lack of medical
      information that can be otherwise found in a handbook. The choice ofa less
      optimal but more familiar approach to patient management due to lack of knowledge
      was reported by 37%. Eighty-eight percent of responders believe that having a
      point-of-care information system for the anaesthesiologists in the operating room
      is either important or very important. CONCLUSIONS: This preliminary survey
      demonstrates that lack of knowledge of anaesthesiologists may be a significant
      source of medical errors in the operating room, and suggests that a point-of-care
      information system for the anaesthesiologist may be of value.

PMID- 15717708
TI  - Induced hypotension for tympanoplasty: a comparison of desflurane, isoflurane and
      sevoflurane.
AB  - BACKGROUND AND OBJECTIVES: This prospective, randomized, double-blinded study was
      designed to compare the effects of desflurane, isoflurane and sevoflurane when
      combined with remifentanil for induced hypotension on surgical conditions and
      operative field during tympanoplasty. METHODS: Sixty patients undergoing
      tympanoplasty were enrolled in the study. The patients were randomized into three
      groups of 20 each to receive the inhalation anaesthetics desflurane, isoflurane
      or sevoflurane. Propofol 2 mg kg(-1) was administered for induction of
      anaesthesia in all groups. All patients received a continuous infusion of
      remifentanil which was titrated between 0.2 and 0.5 microg kg(-1) min(-1) to
      achieve a mean blood pressure (BP) of 60-70 mmHg. Nitroglycerine was infused if
      this BP could not be achieved. Arterial pressures were recorded continuously
      throughout the operation. Surgical conditions were assessed every 20 min by the
      blinded surgeon using a six-point category scale (0-5). RESULTS: One patient in
      the desflurane group and two patients in isoflurane group required nitroglycerine
      to maintain desired mean BP. Sustained controlled hypotension was sufficient in
      all of the groups throughout surgery. Category scale scores were < or =3
      throughout the study, except one patient in the sevoflurane group who had a score
      of 4 at the 60th minute of the operation. No difference was found among groups
      when haemodynamic parameters and surgical category scale scores were compared.
      There were no postoperative respiratory and circulatory complications.
      CONCLUSION: Desflurane, sevoflurane or isoflurane combined with remifentanil
      provided adequate induced hypotension and similar operating conditions and any of
      them could be safely and equally used in anaesthesia for tympanoplasty.

PMID- 15717709
TI  - Three-dimensional cervical spine movement during intubation using the Macintosh
      and Bullard laryngoscopes, the bonfils fibrescope and the intubating laryngeal
      mask airway.
AB  - BACKGROUND AND OBJECTIVE: Cervical spine movement may be limited for
      morphological reasons or through injury. The major goal of the present study was
      to evaluate the three-dimensional cervical spine movement during intubation with
      a Macintosh or Bullard laryngoscope, a Bonfils fibrescope or an intubating
      laryngeal mask using an ultrasound-based motion system. METHODS: Forty-eight
      patients without any history of cervical spine problems who had to undergo
      elective surgery in general anaesthesia were intubated using a Macintosh or
      Bullard laryngoscope, a Bonfils fibrescope or an intubating laryngeal mask
      airway. During intubation, cervical motion as well as overall time to intubation,
      number of attempts, and postoperative complaints were noted. RESULTS: The range
      of cervical spine motion during intubation, especially concerning extension,
      using the Macintosh laryngoscope was much greater (22.5 degrees +/- 9.9 degrees)
      than using Bullard (3.4 degrees +/- 1.4 degrees), Bonfils (5.5 degrees +/- 5.0
      degrees) or intubating laryngeal mask (4.9 degrees +/- 2.1 degrees). Time to
      intubate the trachea using Bonfils (52.1 +/- 22.0 s) and intubating laryngeal
      mask (49.8 +/- 18.7 s) were much longer than with Macintosh (18.9 + 7.1s) and
      Bullard laryngoscope (16.1 + 6.2 s) (significance level: 0.05). CONCLUSIONS: Our
      findings suggest that the Bullard laryngoscope may be a useful adjunct to
      intubate patients with cervical spine injuries. In elective situations when time
      to intubation is not critical Bonfils as well as intubating laryngeal mask airway
      should also be considered as serious alternatives to direct laryngoscopy.

PMID- 15717710
TI  - Prophylactic magnesium sulphate vs. lidocaine during off-pump coronary artery
      bypass grafting.

PMID- 15717711
TI  - Small-dose ketamine decreases postoperative morphine requirements.

PMID- 15717712
TI  - Diagnosis of underlying mechanisms of diffuse microvascular bleeding allows
      targeted therapy.

PMID- 15717713
TI  - Anesthetic management of a patient with histiocytosis X and pulmonary
      complications during Caesarean section.

PMID- 15717714
TI  - General anaesthesia in a patient with motor neuron disease.

PMID- 15717715
TI  - An assessment of compliance with surgical prophylaxis protocols in a hospital.

PMID- 15717716
TI  - Fibreoptic intubation in patients after radiotherapy for carcinoma of the head
      and neck: difficulty and predictability.

PMID- 15717717
TI  - Advances in the surgical management of early stage invasive breast cancer.

PMID- 15717718
TI  - R-MC46 monoclonal antibody stimulates adhesion and phagocytosis by rat
      macrophages.
AB  - BACKGROUND: In our previous experiments it was shown that R-MC46 monoclonal
      antibody (mAb), produced at our Institute, stimulated homotypic aggregation of
      rat granulocytes and production ofproinflammatory cytokines. The aim of this
      study was to examine antigen expression and function, recognized by R-MC46 mAb on
      macrophages. METHODS: The expression of R-MC46 antigen on thymic and peritoneal
      macrophages was investigated using immunocytochemistry and flow cytometry
      methods. Its biochemical characterization was performed by Western blot. The
      ability of R-MC46 mAb to modulate adhesion and phagocytosis by macrophages was
      studied by using co-culture experiments with autologous thymocytes. RESULTS: R
      MC46 mAb stained thymic macrophages more strongly than peritoneal macrophages.
      After in vivo treatment of peritoneal macrophages with Pristane, a significant up
      regulation of the R-MC46 antigen expression was observed Western blot analysis
      showed that the mAb recognized a low molecular weight antigen of about 5.5 kDa. R
      MC46 mAb significantly enhanced binding and phagocytosis of thymocytes by both
      thymic and peritoneal macrophages. These processes were completely blocked by
      WT.3 (anti-CD18) mAb. The stimulation of binding thymocyte to macrophages was
      higher with the use of thymic macrophages,while the phagocytosis of these cells
      was higher in the presence of peritoneal macrophages. CONCLUSION: R-MC46 mAb
      recognized a new molecule expressed by rat macrophages. The antigen is most
      probably involved in 82 integrin-mediated adhesion and phagocytosis, as well as
      proinflammatory functions of macrophages.

PMID- 15717719
TI  - Late ventricular potentials in risk assessment of the occurrence of complex
      ventricular arrhythmia in patients with myocardial infarction and heart failure.
AB  - AIM: To determine the prognostic significance of late ventricular potentials on
      signal-averaged electrocardiogram and left ventricular ejection fraction for the
      occurrence of complex ventricular arrhythmia in patients treated with accelerated
      tissue-type plasminogen activator, using the rapid protocol, within six months of
      acute myocardial infarction. METHODS: In this analytic observational prospective
      study patients were divided into four groups: patients with left ventricular
      ejection fraction bellow 40% and late ventricular potentials, patients with left
      ventricular ejection fraction bellow 40% and without late ventricular potentials,
      patients with left ventricular ejection fraction over 40% and late ventricular
      potentials, and patients with left ventricular ejection fraction over 40% and
      without late ventricular potentials. Complex ventricular arrhythmias (Lown grade
      IVa, IVb, and V) were recorded using standard electrocardiography and 24-hour
      Holter monitoring 21, 60, and 90 days after acute myocardial infarction,
      respectively. Serial recordings of signal-averaged electrocardiogram were
      obtained 30, 90, and 180 days after acute myocardial infarction. Left ventricular
      ejection fraction was determined by echocardiography between 15 and 21 days after
      acute myocardial infarction. Multivariant logistic regression analysis was used
      to evaluate the relation between late ventricular potentials and left ventricular
      ejection fraction with the occurrence of complex ventricular arrhythmias.
      Sensitivity, specificity, positive and negative predictive values of late
      ventricular potentials and left ventricular ejection fraction for the occurrence
      of complex ventricular arrhythmias were determined. RESULTS: The prospective
      study included 80 patients (73% men), mean age 64 +/- 3.5 years. Complex
      ventricular arrhythmias were recorded in 34 (42.5%) of patients, all 17 (50%) of
      which were from the first group (p < 0.01). Complex ventricular arrhythmias were
      recorded in 25 (73.5%) patients with late ventricular potentials, and in 23
      (67.6%) patients with left ventricular ejection fraction bellow 40%. Left
      ventricular ejection fraction bellow 40% and late ventricular potentials
      represented independent predictors for the occurrence of complex ventricular
      arrhythmias (RR = 14.33, p < 0.01). When combined with left ventricular ejection
      fraction bellow 40%, late ventricular potentials had sensitivity (0.50),
      specificity (0.93), and positive predictive accuracy (0.85) higher than late
      ventricular potentials alone (0.44, 0.67, and 0.37, respectively) for the
      occurrence of complex ventricular arrhythmias following acute myocardial
      infarction. CONCLUSION: In this study, late ventricular potentials in patients
      with left ventricular ejection fraction bellow 40% represented the independent
      predictor for the occurrence of complex ventricular arrhythmias in the first six
      months after the first myocardial infarction treated with accelerated tissue-type
      plasminogen activator, using the rapid protocol.

PMID- 15717720
TI  - [Disturbances of protein C activity in abdominal sepsis: diagnostic and
      predictive importance].
AB  - BACKGROUND: Despite improved diagnostic modalities, potent antibiotics, modern
      intensive care, and aggressive surgical treatment, more than one third of
      patients still die of severe secondary peritonitis. Clinical difficulties in the
      treatment of abdominal sepsis were related to inherent problems of limited
      clinical signs and the rapid spread of infection. An inflammatory process is
      often well under way before the presence of clinical signs and symptoms of
      sepsis. The aim of this prospective study was to assess diagnostic and prognostic
      significance of protein C in abdominal sepsis. METHODS: Twenty-two patients with
      severe intraabdominal infections with sepsis syndrome were treated surgically as
      compared to 15 patients with hernia repair (control group). During the study, the
      following parameters were analyzed daily: protein C, AT III, plasminogen, alfa-2
      antiplasmin, HMWK, C5a and C5-B9 complement, C1-inhibitor, CRP. RESULTS. The mean
      APACHE II score was 17 points, with actual mortality rate of 23%. Each parameter
      evaluated in the abdominal sepsis group differed from the one evaluated in the
      control group to a great extent (p = 0.001). The results and multivariate
      regression statystical analysis confirmed the following parameters as sensitive
      biological markers of septic cascade (p < 0.0001-0.026): protein C, AT III, HMWK,
      C1-inhibitor and C5-B9 complement. According to the results the low level of
      protein C consistently correlated with disease severity and suggested the
      development of septic shock and poor outcome. CONCLUSION: Early diagnosis of
      plasma proteolytic disturbances was very important, from the diagnostic and
      predictive point of view, in abdominal sepsis. According to the results protein C
      was the most significant marker of sepsis and early predictor of the outcome of
      septic complications during severe intraabdominal infections (r = 0.761; p =
      0.0001).

PMID- 15717721
TI  - [Potential role of cholesterol in distinguishing malignant from benign pleural
      effusion].
AB  - Cholesterol and carcinoembryonic antigen (CEA) levels in pleural effusion and
      sera, were measured in 199 patients with pleural effusions of various origins.
      Malignant cause was found in 93, and nonmalignant in 106 patients. Mean
      cholesterol level in sera of patient with malignant disease was 5.0 +/- 0.93
      mmol/L, and in nonmalignant group 4.34 +/- 1.32 mmol/L. The difference was not
      statistically significant. Mean cholesterol level in nonmalignant pleural
      effusions was higher thAn those in malignant (2.51 +/- 1.23 mmol/L; and 2.28 +/-
      1.06 mmol/L), but the difference was also not significant. Average pleural
      fluid/serum cholesterol ratio (Holl/S) in nonmalignant group was 0.61 +/- 0.32
      and in malignant group 0.46 +/- 0.22. The difference between those mean values
      was significant. Higher ratio, at the cut off value of 0.5 was found in 79/106
      and in 25/93 malignant patients. Calculated sensitivity was 75%, specificity 73%,
      positive predictive value 76%, negative predictive value 65% and accuracy 69%.
      Significant negative correlation between Holi/S and pleural fluid CEA was found
      (p < 0.05). It was assumed that pleural fluid/serum cholesterol ratio lower than
      0.5 could be of great benefit, as an additional test in the differentiation of
      malignant from benign pleural effusion.

PMID- 15717722
TI  - [Correlation between echo morphological carotid plaque characteristics and
      neurological symptoms].
AB  - A group of 72 patients with 111 asymptomatic carotid stenoses (ACS), mean age
      65.42 +/- 9.21 and of 36 patients with 58 symptomatic carotid stenoses (SKS),
      mean age 67.63 +/- 8.79 were analyzed prospectively during a three-years follow
      up period. All patients underwent color duplex scan sonography (CDS), carotid
      arteriography, computed tomography scan (CT), and neurological examination. The
      aim of the study was to analyze correlation between echo plaque morphology
      (degree and plaque quality) and neurological symptoms and objective neurological
      disorders, as well as value of CDS method to appreciate carotid stenosis
      characteristics. The results analysis showed significantly higher ACS in the
      group of 30-49% stenoses, but significantly higher SCS in the group of 70-89% and
      more than 90% stenoses. Fibrous plaque was more frequent in the ACS group, while
      exulceration and mix plaque were more frequent in the SCS group. Significantly
      higher number of clinical CVI cases, deaths, and ischemic lesion registered
      during CT were reported in the SCS group than in the ACS group. CDS showed 92%
      sensitivity, 90% specificity, and 92% diagnostic accuracy in the assessment of
      stenosis growth. Morphological characteristics of carotid plaques, significantly
      correlated with neurological disorders, were stenoses more than 70%, plaque
      exulceration, mix plaque, and plaque stenoses more than 50%.

PMID- 15717723
TI  - [Treatment of 36 cases of thrombotic thrombocytopenic purpura].
AB  - Thirty-six patients (pts.) with thrombotic thrombocytopenic purpura (TTP) were
      treated between May 1990 and May 2003. There were 31 women and 5 men; the average
      age was 37 years. Twenty-five cases were idiopathic and 11 secondary (3 infection
      -related, 5 occurred during pregnancy and 3 were drug--associated). The mean lag
      period between the first symptoms and the diagnosis was 8.5 days (in 14 pts. < or
      = 5; in 22 > 5). On diagnosis neurological symptoms were present in 31, bleeding
      in 33, fever in 21 and renal impairment in 27 patients. The mean hemoglobin was
      67.5 g/L, the mean platelet count was 10 x 10(9)/L, and the mean reticulocytosis
      was 17%. The mean serum LDH was 1457 IU. Treatment included plasma exchange (PE)
      in 24 pts. and only plasma infusions in 12 pts. There were 24 complete responders
      (20 on PE) and 12 deaths (4 on PE); PE significantly improved survival (p <
      0.01). There were 5 treatment-related complications due to the infection and
      bleeding, 17 exacerbations and 4 relapses. The mean time delay before the onset
      of symptoms and the treatment initiation lasted for 9 days suggesting the poor
      disease recognition; the mean time delay from diagnosis to PE institution was 6
      days, indicating postponed PE. The mean treatment duration in all patients was 18
      days; the mean number of PE cycles needed for the platelet count stabilization
      was 9. Good prognostic indicators of survival were: the longer prodromal period
      (> 5 days), the secondary form of TTP and the absence of coma at presentation.
      The use of PE significantly improved survival. TTP is a severe disorder requiring
      early recognition and diagnosis in general medical care facilities, which should
      lead to the timely treatment with PE.

PMID- 15717724
TI  - [Alcohol consumption, arterial blood pressure and general mortality rate--twenty
      years follow-up study].
AB  - BACKGROUND: Alcohol consumption has both adverse and beneficial effects on health
      and survival. The aim of this prospective study was to examine the association
      between alcohol consumption and arterial hypertension as well as general
      mortality rate. METHODS: The study included 286 participants, middle-aged men and
      women examined in 1974, and again in 1994 during twenty years of follow-up (mean
      age at the beginning of the study 43.61 +/- 7.09 years). Alcohol consumption was
      assessed by the specific questionnaire. Consumption levels were grouped into
      three categories: rare drinkers (consuming less than 6 drinks a week), moderate
      drinkers, who consume 1-2 alcohol drinks a day and heavy drinkers (consumers of 3
      or more drinks a day). RESULTS: In both phases of the follow-up the lowest values
      of systolic and diastolic pressure were recorded in the group with moderate
      alcohol consumption, and the highest values in the group with excessive
      consumption. The observed differences were statistically significant. The general
      mortality rates were the highest among participants reporting excessive alcohol
      consumption (relative risk 3.2; 95% confidence interval 1.84-5.62), and among the
      abstainers (relative risk 1.8; 95% confidence interval 0.99-3.36), compared to
      the moderate consumption group. CONCLUSION: Analysis of the obtained results
      suggested the protective effect of moderate alcohol consumption on cardiovascular
      system.

PMID- 15717725
TI  - [Soldier's social adaptation during the military service].
AB  - Soldier's social adaptation includes his interpersonal relationships with his
      environment integration into the military community and the ability to fulfill
      his role in the military environment and to function adequately outside of it.
      The aim of this study was to establish the dynamics of soldier's social
      adaptation during the military service. The study involved soldiers of two
      platoons of the Armed Forces of Serbia and Montenegro, divided into three groups
      according to the period of the study: after the first month, after the basic
      training and at the end of the military service. The instruments applied for the
      study were sociodemografic questionnaire and Social Adaptation Self-evaluation
      Scale. Statistical analysis of the obtained data was done using Stident's t-test.
      The results of the study that soldier's contentment with his professional role
      and with the quality of his interpersonal relations was highest during the basic
      training, but the quality of leisure activities was lowest at the end of the
      military service.

PMID- 15717726
TI  - [The most often causes of odontogenic maxillary sinusitis].
AB  - In the period 2000-2002, 40 patients with odontogenic sinusitis were examined at
      the Institute for ENT and Maxillofacial Surgery, Clinical Centre of Serbia.
      Oroantral communication was detected in 40% of the patients, oroantral fistula in
      35%, sinus foreign bodies in 15% and other conditions in 10% of the cases. The
      extraction of the upper lateral teeth was the cause of odontogenic sinusitis in
      65% of the cases. Given the specific tooth, the first upper molar was the most
      often cause of the condition, i.e., in 40% of cases. Odontogenic sinusitis as the
      complication of the oral cavity surgery was found in 85% of the patients.

PMID- 15717727
TI  - [Chronic instability of the knee joint].

PMID- 15717728
TI  - [Physiological role and clinical significance of serum cholinesterase].

PMID- 15717729
TI  - [The role and significance of trace elements in the pathogenesis of
      atherosclerosis].

PMID- 15717730
TI  - [The most frequent stress syndromes in soldiers in war].

PMID- 15717731
TI  - [Brown tumor of the maxilla in patient with secondary hyperparathyroidism].
AB  - Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by
      hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in
      mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is
      the result of osteoclastic activity due to an increased activity of parathyroid
      hormone. A 25-years-old male patient was operated on due to clinicaly and
      radiographicaly obvious maxillary tumor and increased values of parathyroid
      hormon (PTH-1 050 ng/l). The level of calcium in blood was normal (Ca 2.34
      mEq/L). The patient was dialyzed for years because of the chronic renal failure.
      Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of
      secondary hyperparathyroidism due to the chronic renal failure. The operation of
      the upper jaw had been performed before parathyroidectomy, due to an excessive
      growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was
      followed by the regression of remaining bony lesions.

PMID- 15717732
TI  - [Infective endocarditis of a rare etiology (Serratia marcescens)].
AB  - Infective endocarditis (IE) is a unique diagnostic and therapeutic challenge. It
      is a severe disease, fatal before penicillin discovery. Atypical presentations
      frequently led to delayed diagnosis and poor outcome. There was little
      information about the natural history of the vegetations during medical treatment
      or the relation of morphologic changes in vegetation to late complications.
      Application of a new diagnostic criteria and echocardiography, increased the
      number of definite diagnosis. Trans-thoracic and trans-esophageal
      echocardiography had an established role in the management of patients with IE.
      The evolution of vegetation size, its mobility, and consistency, the extent of
      the disease, and the severity of valvular regurgutation were related to late
      complications. With therapeutic options including modern antibiotic treatment and
      early surgical intervention IE turned out to be a curable disease. Reduction in
      mortality also depended on prevention. Antibiotic prophylaxis of IE was
      important, but low mortality was also the result of early treatment, especially
      in the event of early recognition of symptoms and signs of the disease.

PMID- 15717733
TI  - [Cognitive-behavioral therapy of conversion aphonia].
AB  - Although a common disease, conversion disorder still calls attention in the
      clinical practice. A case of conversion disorder, diagnosed as a psychogenic
      aphonia that persisted for a week, was reported in this paper. A 21-year-old
      woman developed symptoms after breaking off a long-lasting relationship with her
      boy-friend. History revealed that she was introvert with high neuroticism and
      communication problems. Cognitive-behavioral therapy was used. After the positive
      reinforcement in the therapy of her aphonia, assertion training for the
      development of communication skills was performed. In the end, cognitive
      restructuring was used to prevent relapse in regard to her actual life situation
      of being a refugee preparing for immigration to Australia.

PMID- 15717734
TI  - Modeling of drug release from polymeric delivery systems--a review.
AB  - Polymeric drug delivery platforms have been receiving increasing attention in the
      past decade. The pharmaceutical industry is evaluating modes of delivery for
      their prized therapeutics at every step of the design cycle. Not only can the
      drug delivery platform transport drug molecules effectively, it can also improve
      patient compliance, offer greater patient convenience, and extend product
      lifecycles as patents expire. A large number of successful drug delivery systems
      have been developed as a result of an almost arbitrary selection of constituents
      and configurations. However, the development of advanced drug delivery systems
      relies on a judicious and careful selection of components, configurations, and
      geometries, which can be facilitated through mathematical modeling of controlled
      release systems. Mathematical modeling aids in predicting the drug release rates
      and diffusion behavior from these systems by the solution of an appropriate
      model, thereby reducing the number of experiments needed. It also aids in
      understanding the physics of a particular drug transport phenomenon, thus
      facilitating the development of new pharmaceutical products. The objective of
      this article is to review the spectrum of mathematical models that have been
      developed to describe drug release from polymeric controlled release systems. The
      mathematical models presented in this article have been grouped under diffusion
      controlled systems, swelling controlled systems, and erosion controlled systems
      as proposed by Langer and Peppas. Simple empirical or semi-empirical models and
      complex mechanistic models that consider diffusion, swelling, and erosion
      processes simultaneously are presented.

PMID- 15717735
TI  - Advantages of liposomal delivery systems for anthracyclines.
AB  - Liposomes, closed vesicular structures consisting of one or more lipid bilayers,
      have generated a great deal of interest as drug delivery vehicles. In particular,
      they have been investigated for their ability to improve the delivery of
      chemotherapeutic agents to tumors, in efforts to increase therapeutic efficacy
      and decrease toxicity to normal cells. Development of liposomal chemotherapeutic
      agents has, in the past, been hindered primarily by the rapid uptake of liposomes
      by the reticuloendothelial system. Numerous strategies that seek to either
      exploit or avoid this phenomenon have been used. As a result, several liposomal
      chemotherapeutic agents are now available in the clinic. STEALTH, a novel
      liposomal system coated with polyethylene glycol, avoids uptake by the
      reticuloendothelial system, thus improving drug delivery to the tumor while
      decreasing toxicity. In pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]),
      this delivery system encapsulates doxorubicin within polyethylene glycol-coated
      liposomes, leading to promising new applications for a well-established drug.
      Liposome-encapsulated doxorubicin citrate complex (Myocet [NPLD]), another
      liposomal delivery system for doxorubicin, lacks the polyethylene glycol coating,
      resulting in much shorter circulation times than those of PLD. Daunorubicin
      citrate liposome (DaunoXome [DNX]) contains daunorubicin encapsulated in a
      smaller liposome of a different lipid composition. It has circulation times
      between those of PLD and NPLD. This article reviews the advantages of liposomal
      delivery systems in general and the divergent approaches that have been taken in
      developing these agents.

PMID- 15717736
TI  - Pegylated liposomal doxorubicin: proof of principle using preclinical animal
      models and pharmacokinetic studies.
AB  - Encapsulation of doxorubicin in polyethylene glycol-coated liposomes
      (Doxil/Caelyx [PLD]), was developed to enhance the safety and efficacy of
      conventional doxorubicin. The liposomes alter pharmacologic and pharmacokinetic
      parameters of conventional doxorubicin so that drug delivery to the tumor is
      enhanced while toxicity normally associated with conventional doxorubicin is
      decreased. In animals and humans, pharmacokinetic advantages of PLD include an
      increased area under the plasma concentration-time curve, longer distribution
      half-life, smaller volume of distribution, and reduced clearance. In preclinical
      models, PLD produced remission and cure against many cancers including tumors of
      the breast, lung, ovaries, prostate, colon, bladder, and pancreas, as well as
      lymphoma, sarcoma, and myeloma. It was also found to be effective as adjuvant
      therapy. In addition, it was found to cross the blood-brain barrier and induce
      remission in tumors of the central nervous system. Increased potency over
      conventional doxorubicin was observed and, in contrast to conventional
      doxorubicin, PLD was equally effective against low- and high-growth fraction
      tumors. The combination of PLD with vincristine or trastuzumab resulted in
      additive effects and possible synergy. PLD appeared to overcome multidrug
      resistance, possibly as the result of increased intracellular concentrations and
      an interaction between the liposome and P-glycoprotein function. On the basis of
      pharmacokinetic and preclinical studies, PLD, either alone or as part of
      combination therapy, has potential applications to treat a variety of cancers.

PMID- 15717737
TI  - Use of liposomal anthracyclines in Kaposi's sarcoma.
AB  - Conventional chemotherapy regimens for the treatment of advanced Kaposi's sarcoma
      (KS) show limited efficacy and considerable toxicity. Liposomal anthracyclines
      with potential utility in KS include pegylated liposomal doxorubicin
      (Doxil/Caelyx [PLD]), daunorubicin citrate liposome (DaunoXome [DNX]), and
      nonpegylated liposomal doxorubicin (Myocet [NPLD]). Preclinical data showed that
      pegylated liposomes accumulate preferentially in highly vascularized KS lesions.
      In randomized clinical trials, PLD induced higher response rates than did the
      conventional combination chemotherapy regimens, bleomycin + vincristine (BV) and
      BV + conventional doxorubicin (ABV); DNX produced a response rate comparable to
      that of ABV. NPLD has not been compared with conventional chemotherapy for KS.
      PLD and DNX were associated with less toxicity compared with BV or ABV, including
      less alopecia and fewer gastrointestinal and neurologic side effects. Grade 3/4
      myelosuppression was common with both PLD and DNX; stomatitis and infusion
      reactions occurred with PLD treatment, but hand-foot syndrome was relatively
      infrequent in the dose schedules used for KS. Health-related quality of life was
      improved in several domains in patients treated with PLD or DNX compared with
      ABV.

PMID- 15717738
TI  - Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.
AB  - Preclinical studies have established the pharmacologic advantages of liposomal
      anthracyclines, including pharmacokinetic profiles after bolus dosing that
      resemble continuous infusion of conventional anthracyclines, increased drug
      concentrations in tumor cells compared with the surrounding tissues, and reduced
      toxicity relative to conventional anthracycline treatment. Based on these
      studies, many phase I and phase II clinical trials were conducted to assess the
      safety and potential activity of liposomal anthracyclines in the management of
      both solid and hematologic tumors. These studies provided valuable insight into
      the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated
      liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome
      [DNX]) over a range of doses, either as single-agent therapy or in combination
      with other cytotoxic agents. Other liposomal anthracyclines in development may be
      well tolerated but their activity remains to be elucidated by clinical trials.
      The available data also suggest that liposomal anthracyclines have activity not
      only against tumor types with known sensitivity to conventional anthracyclines,
      but also potentially for tumors that are typically anthracycline-resistant.
      Despite the availability of clinical data from a wide variety of tumor types and
      patient populations, further studies of liposomal anthracycline therapy are
      needed to fully establish their safety, efficacy, and dosing in the treatment of
      these patients.

PMID- 15717739
TI  - Liposomal anthracycline treatment for ovarian cancer.
AB  - Platinum/taxane regimens induce high response rates and prolong survival in women
      with ovarian cancer. After recurrence, however, response to second-line
      chemotherapy is limited. Pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), is
      the only liposomal anthracycline indicated for second-line treatment of platinum-
      and paclitaxel-refractory ovarian cancer. Response rates ranged from 14% to 20%
      in nonrandomized trials of this patient population. In a large phase 3 randomized
      trial, single-agent PLD and topotecan had similar efficacy overall in response
      rates, but PLD-treated patients had significantly improved overall survival
      compared with topotecan with a pronounced advantage in platinum-sensitive
      patients. Another randomized trial reported that PLD and paclitaxel were
      comparable with regards to response rate, progression-free survival, and overall
      survival, regardless of the degree of platinum sensitivity. Additional
      nonrandomized trials of PLD in combination with other active agents resulted in
      response rates ranging from 20% to 76%. PLD is generally well tolerated and its
      side-effect profile compares favorably with other commonly used chemotherapeutic
      agents in this clinical setting. Proper dosing and monitoring may further enhance
      tolerability while preserving the efficacy of this versatile agent for ovarian
      cancer.

PMID- 15717741
TI  - Role of liposomal anthracyclines in the treatment of multiple myeloma.
AB  - Patients with multiple myeloma (MM) typically respond to initial chemotherapy,
      but almost all patients relapse with a median survival of approximately 5 years.
      Combining vincristine and conventional doxorubicin with oral dexamethasone (VAD)
      or reduced-dose dexamethasone (VAd) provides rapid response in many patients, but
      its use is limited by toxicity concerns and the inconvenience of continuous
      infusions in each cycle. Use of pegylated liposomal doxorubicin (Doxil/Caelyx
      [PLD]) and vincristine intravenous injection with oral dexamethasone (DVD) or
      reduced-dose dexamethasone (DVd) is safe and effective for the management of
      newly diagnosed or relapsed/refractory MM. Controlled trials showed that DVD/DVd
      is at least as effective as VAD/VAd for the treatment of MM, but DVd is
      associated with less neutropenia and alopecia in addition to requiring fewer days
      in the hospital or clinic for drug administration. DVd therapy has also been
      reported to be associated with an antiangiogenic effect not observed with VAD.
      Another liposomal anthracycline, liposomal daunorubicin (DaunoXome [DNX]), has
      been investigated in MM and preliminary data suggest that it is safe and
      effective, but studies comparing it with other regimens have not been reported.
      Early results from ongoing trials suggest that adding thalidomide, bortezomib, or
      other immune modulators to PLD-based chemotherapy may improve efficacy.

PMID- 15717740
TI  - The role of the liposomal anthracyclines and other systemic therapies in the
      management of advanced breast cancer.
AB  - For patients whose breast cancers are not responsive to endocrine therapy, there
      are a large number of cytotoxic drugs that will induce a response. In spite of
      the introduction of new, very active drugs such as the taxanes, vinorelbine,
      capecitabine, gemcitabine, and trastuzumab, the anthracyclines are still as
      active as any--and more active than most--drugs used to treat breast cancer.
      Their inclusion in combinations to treat early and advanced disease prolongs
      survival. However, they cause nausea, vomiting, alopecia, myelosuppression,
      mucositis, and cardiomyopathies. There is no evidence that increasing the dose of
      conventional anthracyclines or any other of the cytotoxics beyond standard doses
      will improve outcomes. Schedule may be more important than dose in determining
      the benefit of cytotoxics used to treat breast cancer. Weekly schedules and
      continuous infusions of 5-fluorouracil and doxorubicin may have some advantages
      over more intermittent schedules. Liposomal formations of doxorubicin reduce
      toxicity, including cardiotoxicity; theoretically they should also be more
      effective because of better targeting of tumor over normal tissues. Both
      pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) and liposomal doxorubicin
      (Myocet [NPLD]) appeared to be as effective as conventional doxorubicin and much
      less toxic in multiple phase II and phase III studies. PLD has been evaluated in
      combinations with cyclophosphamide, the taxanes, vinorelbine, gemcitabine, and
      trastuzumab, and NPLD has been evaluated in combination with cyclophosphamide and
      trastuzumab. Both liposomal anthracyclines are less cardiotoxic than conventional
      doxorubicin. The optimal dose of PLD is lower than that of conventional
      doxorubicin or NPLD. Patients treated with PLD have almost no alopecia, nausea,
      or vomiting, but its use is associated with stomatitis and hand-foot syndrome,
      which can be avoided or minimized with the use of proper dose-schedules. In
      contrast, the optimal dose-schedule of NPLD is nearly identical to that of
      conventional doxorubicin. The toxicity profile of NPLD is similar to that of
      conventional doxorubicin, but toxicities are less severe and NPLD is better
      tolerated than conventional doxorubicin at higher doses.

PMID- 15717742
TI  - Cardiac safety of liposomal anthracyclines.
AB  - Conventional anthracyclines are active against many tumor types, but
      cardiotoxicity related to the cumulative dose may limit their use; this is
      particularly problematic for patients with risk factors for increased toxicity,
      for those who have received any anthracycline in the past, or for those who are
      to receive other cardiotoxic agents. Preclinical studies determined that
      encapsulating conventional anthracyclines in liposomes reduced the incidence and
      severity of cumulative dose-related cardiomyopathy while preserving antitumor
      activity. In controlled clinical trials, the risk of cardiotoxicity was
      significantly lower when nonpegylated liposomal doxorubicin (Myocet [NPLD]) was
      substituted for conventional doxorubicin, but the risk was not significantly
      different when NPLD was used in place of conventional epirubicin. Direct
      comparisons to conventional doxorubicin therapy showed comparable efficacy but
      significantly lower risk of cardiotoxicity with pegylated liposomal doxorubicin
      (Doxil/Caelyx [PLD]) therapy. Retrospective and prospective trials have not
      identified a maximum "cardiac safe" dose of PLD, despite use of cumulative doses
      exceeding 2,000 mg/m2 in some patients. Liposomal daunorubicin (DaunoXome [DNX])
      may be associated with a lower risk of cardiotoxicity than conventional
      anthracyclines, but comparative trials are not available. With respect to
      combination chemotherapy, early results of clinical trials suggest that combining
      trastuzumab or a taxane with NPLD or PLD instead of a conventional anthracycline
      significantly reduces cardiotoxicity risk without reducing chemotherapeutic
      efficacy. Further results are eagerly awaited from ongoing controlled trials of
      cardiac safety with long-term liposomal anthracycline therapy, either alone or in
      combination with other potentially cardiotoxic agents.

PMID- 15717743
TI  - Liposomal anthracycline administration and toxicity management: a nursing
      perspective.
AB  - Nursing care of the patient receiving chemotherapy includes patient education and
      drug administration, as well as ongoing assessment, early identification, and
      intervention for side effects. Two liposomal anthracyclines are available in the
      United States, pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) and liposomal
      daunorubicin (DaunoXome [DNX]). Because of their unique liposomal formulations,
      the administration and toxicity profiles of these agents are different from those
      of conventional anthracyclines, as well as each other. Common severe toxicities
      of conventional anthracycline treatment such as nausea/vomiting, alopecia, and
      neutropenia are less frequent and less severe during liposomal anthracycline
      treatment, and cumulative-dose cardiotoxicity is rare, particularly with PLD
      therapy. Dose-related adverse events with liposomal anthracycline therapy include
      stomatitis and neutropenia, and more frequent doses of PLD are associated with
      hand-foot syndrome. Ongoing nursing assessment, patient education, and
      adjustments to the dose or dose-schedule can reduce the severity or frequency of
      these toxicities. Nurses must be aware of the unique characteristics of liposomal
      anthracycline therapy to provide optimal patient education and nursing care.

PMID- 15717744
TI  - Pharmacoeconomics of liposomal anthracycline therapy.
AB  - Pharmacoeconomic analyses are being used with greater frequency in clinical
      oncology trials. These analyses provide guidelines for prioritizing competing
      interventions and allocating health care resources, particularly when deciding
      whether to use a drug with a higher acquisition cost. For liposomal
      anthracyclines, the competing treatments are other liposomal anthracyclines and
      nonliposomal chemotherapy agents with similar activity. Pharmacoeconomic analyses
      of data from clinical trials in patients with Kaposi's sarcoma determined that
      the overall cost to achieve objective response was substantially lower with
      pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) than with liposomal
      daunorubicin (DaunoXome [DNX]). Additional economic analyses in patients with
      ovarian cancer showed that PLD has lower overall treatment costs than topotecan
      because it is administered less frequently and requires fewer interventions for
      toxicity. The decision to allocate health care resources to liposomal
      anthracycline treatment must therefore include consideration of cost
      effectiveness and potential cost savings owing to improved tolerability.

PMID- 15717745
TI  - Future directions of liposome- and immunoliposome-based cancer therapeutics.
AB  - Nanoscale drug delivery systems including liposomes, polymers, and other
      nanoparticles provide potential solutions for improved cancer therapeutics. Of
      these drug delivery systems, liposome-based agents, particularly liposomal
      anthracyclines, have had the greatest impact in oncology to date. Current
      liposomal drugs evolved from a number of design strategies for improved
      biodistribution over free drugs. Reticuloendothelial system-targeted formulations
      significantly reduce systemic exposure to high peak levels of free drug, but do
      not facilitate targeting to tumors. Passive or physiologic targeting of drugs to
      tumors is achievable using long-circulating liposomes, including pure lipid
      systems as well as surface-modified formulations designed to resist recognition
      and uptake by reticuloendothelial system cells. The latter, represented by
      pegylated or STEALTH liposomes, circulate for days as stable constructs and
      slowly extravasate in neoangiogenic vessels in tumors, providing a degree of
      passive targeting to tumor tissue. Future liposome therapeutics are building on
      these validated designs as well as on pharmacologic insights into their
      mechanisms of delivery. For example, camptothecin analogues, anti-angiogenesis
      agents, and antisense oligonucleotides each represent rational candidates for
      delivery in highly stabilized and long-circulating liposomes. For such agents,
      pegylated liposome delivery offers improved chemical stability of encapsulated
      drug, enhanced accumulation in tumors, and prolonged drug exposure. True
      molecular targeting can be achieved using liposomes linked to ligands such as
      monoclonal antibody fragments directed against cancer-associated antigens.
      Immunoliposomes combine antibody-mediated tumor recognition with liposomal
      delivery and, when designed for target cell internalization, provide
      intracellular drug release. Recent advances in immunoliposome design include
      rapid selection of phage antibody-derived scFv for targeting, and methods for
      conjugation of ligands to existing US Food and Drug Administration-approved
      liposomal drugs such as pegylated liposomal doxorubicin (Doxil/Caelxy [PLD]). An
      immunoliposome consisting of novel anti-HER2 scFv F5 conjugated to PLD, currently
      in development, selectively binds to and internalizes in HER2-overexpressing
      tumor cells. The modular organization of immunoliposome technology enables a
      combinatorial approach in which a repertoire of monoclonal antibody fragments can
      be used in conjunction with a series of liposomal drugs to yield a new generation
      of molecularly targeted agents.

PMID- 15717747
TI  - Intraoperative cytologic crush preparation findings in craniopharyngioma: a study
      of 72 cases.
AB  - OBJECTIVE: To describe the intraoperative crush preparation and the cytologic
      features of craniopharyngioma and the differential diagnosis. STUDY DESIGN:
      Twelve cases of craniopharyngioma were diagnosed by crush preparation cytology in
      the Department of Pathology, Shiraz Medical School, and formed the basis of this
      study. The patients' ages ranged from 7 to 43 years; 3 were female and 9 male.
      The cytologic findings together with the histologic findings were studied.
      RESULTS: All cases had a high yield of cells, consisting of honeycomb sheets of
      epithelial cells with and without palisading rows of cells, papillary clusters,
      squamous cell clusters, anucleated squames, calcification, multinucleated giant
      cells, cholesterol crystals, glandular or rosettelike structures, ciliated
      columnar cells and spindle cells. The smears were diagnosed as suggestive of
      craniopharyngioma. Histologic sections confirmed the cytologic diagnoses.
      CONCLUSION: Intraoperative cytologic crush preparation findings are helpful in
      the diagnosis of craniopharyngioma, when combined with clinical information.
      Crush preparation cytology is important in the diagnosis of central nervous
      system tumors.

PMID- 15717746
TI  - Impression cytology changes and corneoconjunctival calcification in patients with
      chronic renal failure.
AB  - OBJECTIVE: To evaluate the relationship between corneoconjunctival calcification
      and conjunctival squamous metaplasia in patients with chronic renal failure
      (CRP). STUDY DESIGN: We studied impression cytology in 45 CRF patients on regular
      hemodialysis and 30 age- and sex-matched controls. Specimens were obtainedfrom
      the temporal bulbar conjunctiva using cellulose acetate filter paper. The samples
      were fixed in a mixture of 70% ethyl alcohol, 37% formaldehyde and glacial acetic
      acid and then stained with a combination of periodic acid- Schiff and Gill's
      modified Papanicolaou stain and graded by a masked observer. Corneoconjunctival
      calcification was graded by the Porter-Crombie classification. RESULTS: Of 45
      study patients, 4 (9%) disclosed grade 0, 23 (51%) grade 1, 14 (31%) grade 2 and
      4 grade 3 (9%) impression cytology changes. There was a statistically significant
      difference between the patient and control groups (p < 0.001). Calcium deposits
      were more frequent and extensive in CRF patients than in controls (p = 0.01).
      There was no correlation between impression cytology and calcium deposit grades
      (p = 0.128). However the presence of conjunctival inflammation correlated with
      the existence of extensive squamous metaplasia (p < 0.001). CONCLUSION: The
      severity of conjunctival changes in CRF patients on regular hemodialysis are not
      related to calcium deposition but to acute conjunctival inflammation.

PMID- 15717749
TI  - Dot-ELISA vs. PCR of fine needle aspirates of tuberculous lymphadenitis: a
      prospective study in India.
AB  - OBJECTIVE: To evaluate an in-house dot-enzyme-linked immunosorbent assay (ELISA)
      for confirmation of clinically suspected cases of tuberculous lymphadenitis
      (TBLN). STUDY DESIGN: The study was performed at the postgraduate departments of
      microbiology and pathology of a tertiary-care teaching hospital in India.
      Suspected cases of TBLN were prospectively enrolled. Fine needle aspiration was
      done of enlarged lymph nodes in all patients, and 2 smears were prepared, 1 for
      acid-fast bacillus (AFB) demonstration and the other for cytologic examination.
      The remaining material was tested with in-house dot-ELISA and by IS6110
      amplification with polymerase chain reaction (PCR), for diagnosis of TBLN.
      RESULTS: ELISA was more sensitive and detected 93.2% of cases. PCR and fine
      needle aspiration cytology (FNAC) detected 82.5% and 61.0% cases, respectively.
      AFB positivity was 33.1%. CONCLUSION: Application of dot-ELISA was more sensitive
      but less specific as compared to PCR. PCR, though expensive, should be used in
      problem cases because of its high specificity.

PMID- 15717750
TI  - Cotton block method: one-step method of cell block preparation after fine needle
      aspiration.
AB  - OBJECTIVE: To describe the cotton block method, an easy, inexpensive, 1-step
      method of obtaining a cell block after fine needle aspiration biopsy. STUDY
      DESIGN: Before connection to a 10-mL syringe, the plastic hub of a 22-23-gauge
      needle is filled with the 3-4-mm, woolly tip of a cotton bud. Aspiration is
      performed as described elsewhere. After smear preparation, the material remaining
      in the needle and the material retained in the cotton wool mesh are immediately
      fixed by aspiration ofa fixative fluid (70% alcoholic formaldehyde-acetic acid).
      After fixation, the cotton tip is removed and routinely processed for paraffin
      embedding, and the sections are stained by routine methods used in cytopathology.
      RESULTS: The results demonstrate that the amount and quality of material obtained
      in the cotton wool tip is similar to that in the traditional cell block obtained
      from the pellet after centrifugation of aspirated fluid. CONCLUSION: The method
      is easy to perform and cost effective and is a rapid way to prepare cell blocks
      of high quality, allowing special staining techniques and improving
      cytohistologic correlation.

PMID- 15717748
TI  - Significance of immunocytochemical expression of E-cadherin, N-cadherin and CD44
      in serous effusions using liquid-based cytology.
AB  - OBJECTIVE: To assess the diagnostic utility of E-cadherin (E-cad), N-cadherin (N
      cad) and CD44 to discriminate adenocarcinoma cells from benign and malignant
      mesothelial cells in body cavity fluids and to clarify the origin of cancer
      cells. STUDY DESIGN: A total of 120 ThinPrep (Cytyc Corp., Boxborough,
      Massachusetts, U.S.A.) cytologic specimens of serous effusions, which included 22
      cases of reactive mesothelium, 6 cases of malignant mesothelioma and 92 cases of
      metastatic adenocarcinoma from various sites, were immunostained for E-cad, N-cad
      and CD44. RESULTS: Eighty-three of 92 metastatic adenocarcinomas (90.21%)
      expressed E-cad, while 1 of 6 malignant mesotheliomas and 1 of 22 cases of
      reactive mesothelium were positive for E-cad. All 6 cases of mesothelioma
      expressed N-cad, whereas most cases of metastatic adenocarcinomas were negative.
      CD44 immunoreactivity was seen in 18 of 22 (81.81%) benign effusions and in 21 of
      92 (22.82%) metastatic adenocarcinomas. CONCLUSION: The combination of E-cad, N
      cad and CD44 appears to be a useful panel for distinguishing metastatic
      adenocarcinoma, mesothelioma and reactive mesothelium and also for clarifying the
      exact histogenetic origin of cancer cells. This is of great importance in a few
      otherwise-insoluble cases because of differences in tumor treatment and
      prognosis.

PMID- 15717751
TI  - HER-2/neu evaluation by fluorescence in situ hybridization on destained cytologic
      smears from primary and metastatic breast cancer.
AB  - OBJECTIVE: To evaluate HER-2/neu amplification by fluorescence in situ
      hybridization (FISH) (HER-2/neu by FISH) on archival cytologic smears stained
      with May-Grunwald-Giemsa (MGG) stain. STUDY DESIGN: Cytologic specimens from 69
      breast cancer lesions (48 primary and 21 metastatic), stained with MGG stain for
      routine diagnostic cytology, were destained and subjected to HER-2/neu by FISH.
      Fifteen of the 69 samples were also evaluated by FISH on paired fresh smears.
      RESULTS: HER-2/neu by FISH was successfully assayed in 25 of the 48 primary
      tumors and in 15 of the 21 metastatic lesions, corresponding to an overall
      feasibility of 58%. These cases had been archived between 1 month and 10 years
      prior to FISH analysis. Eight of the 25 primary and 5 of the 15 metastatic tumors
      were amplified. In 15 of the 40 evaluable cases, HER-2/neu was also assessed on
      the corresponding fresh smears: 8 tumors were amplified and 7 unamplified on both
      destained MGG and fresh smears. CONCLUSION: HER-2/neu can be detected by FISH on
      routinely MGG-stained cytologic slides. This approach allows HER-2/neu evaluation
      whenever histologic sections or fresh cytologic material are not available. In
      these cases, HER-2/neu assessment on destained cytologic smears plays a role in
      the selection of targeted therapy.

PMID- 15717752
TI  - Detection of the human telomerase RNA component by in situ hybridization in cells
      from body fluids.
AB  - OBJECTIVE: To apply in situ hybridization (ISH) detection of human telomerase
      reverse transcriptase (hTERT) mRNA expression in abnormal cells in body fluids to
      evaluate its usefulness in the diagnosis of malignant effusions. STUDY DESIGN: We
      investigated the expression of hTERT mRNA by ISH in 33 fluid samples from 30
      patients, including 1 cerebrospinal fluid, 18 pleural fluids, 1 pericardial
      fluid, 12 peritoneal fluids and 1 bronchial washing. Comparison of the results of
      ISH with those of conventional cytologic evaluation was also performed. RESULTS:
      Cytomorphologic examination of the 33 body fluids allowed classification as
      malignant, suspicious, atypical and benign conditions. Among the 17 malignant
      conditions, there were 15 cases positive by both cytology and ISH. There were 9
      discrepant cytology-ISH results in patients with various conditions, including 2
      cases positive by cytology and inconclusive by ISH, 5 cases suspicious by
      cytology and positive by ISH, and 2 cases atypical by cytology and negative by
      ISH. Among the 9 benign conditions, there were 8 cases negative by both cytology
      and ISH and 1 case negative by cytology and positive by ISH. This test was highly
      sensitive (90%) and specific (91 %) and had favorable positive (95%) and negative
      (83%) predictive values. CONCLUSION: Expression of the hTERT mRNA component can
      be easily detected by ISH in malignant cells from body fluids. This method is
      especially useful when the abnormal cellpopulation in the fluid consists of
      limited numbers of suspicious cells that cannot be completely differentiated from
      reactive mesothelial cells and thus may help differentiate true positive cases
      from false negative ones. This ISH method for the detection of expression of the
      hTERT mRNA component may be an ancillary test for early recognition of cancer
      cells in body fluids and thus has potential as a diagnostic adjunct in
      cytopathology.

PMID- 15717753
TI  - Role of fine needle aspiration cytology in the preoperative presumptive diagnosis
      of ameloblastoma.
AB  - OBJECTIVE: To determine the role of fine needle aspiration cytology (FNAC) on the
      preoperative presumptive diagnosis of ameloblastoma. STUDY DESIGN: Sixty-three
      patients, diagnosed preoperatively and postoperatively with ameloblastoma, were
      evaluated between 1990 and 2003. The patients were classified according to
      whether they were diagnosed with ameloblastoma preoperatively or postoperatively,
      on histologic examination. RESULTS: The accuracy rate for ameloblastoma was 0.95%
      for all biopsy methods, while the incisional biopsy rate was 75.00%. Concerning
      clinical diagnosis, ameloblastoma was mistaken mostly (56.41%) for odontogenic
      cysts (22 of 39). CONCLUSION: FNAC should be utilized more commonly on
      intraosseous and soft tissue lesions in the oral and maxillofacial regions, to
      obtain sufficient material. It is convenient, inexpensive and noninvasive as
      compared with other biopsy methods.

PMID- 15717754
TI  - New criterial for cytologic diagnosis of adenoid cystic carcinoma.
AB  - OBJECTIVE: To formulate new criteria for adenoid cystic carcinoma (ADCC). STUDY
      DESIGN: The usefulness of 17 items for a cytologically definitive diagnosis of
      ADCC was examined. The frequency (- - +++) of the 17 items in 18 cases of ADCC
      and 10 non-ADCC cases (pleomorphic adenoma, basal cell adenoma, myoepithelioma
      and epithelial-myoepithelial carcinoma) that displayed mimicking cytology was
      examined cytologically. The total score for cases of ADCC was compared with that
      for non-ADCC cases. RESULTS: The 17 items included broad intercellular spaces
      with adhesion; green, granular/cobwebby cytoplasm with translucent intercellular
      matrix with Papanicolaou staining; coarse hyperchromatin with little nuclear
      clearing; indistinct and partially distinct nucleoli; small nuclei; broad, smooth
      margin (SM) space; and translucent M/HG/SM. All cases with a total score of > 21
      were ADCC (93.8%). All cases with a total score of < 12 were non-ADCC (87.5%).
      CONCLUSION: The 17 items appear to be useful as new criteria for ADCC.

PMID- 15717756
TI  - Cryptococcal lymphadenitis: report of a case with fine needle aspiration
      cytology.
AB  - BACKGROUND: Cryptococcosis is one of the opportunistic infections in AIDS, and
      therefore an expeditious diagnosis is of the utmost importance since once a
      cryptococcal infection disseminates, it becomes life threatening. CASE: A 40-year
      old woman presented with epistaxis, fever and cervical lymphadenopathy for 20
      days. Fine needle aspiration showed reactive lymphoid hyperplasia with plump,
      histiocytoid cells resembling metastatic deposits. The second aspirate showed
      ovoid to spherical, thick-walled structures that stained positive for periodic
      acid-Schiff stain and mucicarmine. CONCLUSION: Lymph node fine needle aspiration
      cytology provides an economical and rather quickly accomplished cytodiagnostic
      result.

PMID- 15717755
TI  - Diagnosis of lymphoma by image-guided needle biopsies: fine needle aspiration
      biopsy, core biopsy or both?
AB  - OBJECTIVE: To determine whether or not concurrent core biopsy adds to results
      obtained from image-guided fine needle aspiration biopsy (FNAB) in cases of
      lymphoma. STUDY DESIGN: Twenty-eight FNABs of lymphomas with adjuvant flow
      cytometry (FC) and concurrent core biopsy were evaluated retrospectively. In each
      case, completeness of diagnosis by FNAB, including phenotyping and grading, where
      appropriate, was reviewed. The contribution of core biopsy to the diagnosis in
      cases where FNAB did not render a complete diagnosis was assessed. Prognostic
      information not available from the FNAB but obtained from the core biopsy was
      also evaluated. RESULTS: FNAB with adjuvant FC gave a complete diagnosis,
      including phenotype and grade, where applicable, in 23 of 28 cases (82%). Core
      biopsy added to the diagnosis in 3 cases. In 1 case, large B-cell lymphoma was
      diagnosed on core biopsy when FNAB was unsatisfactory. In the other 2 cases,
      grade of follicle center cell lymphoma was higher on core biopsy than on FNAB.
      The addition of the information obtained by core biopsy to that obtained by FNAB
      raised the diagnostic accuracy to 93%. Core biopsy was used to assess nodularity,
      which could not be determined on FNAB. Core biopsy was also used to assess
      prognostic markers by immunohistochemistry (Ki-67 and p53); they were not
      available with FC. This was done in 11 cases when requested by the oncologist.
      CONCLUSION: FNAB with adjuvant FC is a useful technique for diagnosing and
      subtyping lymphomas. However, diagnosis and subclassification are often
      insufficient. Core biopsy material provides opportunity for obtaining additional
      diagnostic and prognostic information that may not be easily derived from the
      FNAB. This allows optimal treatment planning in patients for whom excisional
      biopsy is contraindicated.

PMID- 15717758
TI  - Myoepithelioma of the parotid gland initially diagnosed by fine needle aspiration
      cytology and immunocytochemistry: a case report.
AB  - BACKGROUND: Myoepithelioma is a rare, benign tumor of the salivary gland, most
      commonly affecting the parotid gland. Although the cytologic features of
      myoepithelioma are documented in a few case reports, it has rarely been diagnosed
      preoperatively by fine needle aspiration (FNA) cytology. CASE: A 33-year-old man
      presented with a left parotid swelling 2.5 cm in diameter and of about 5 years'
      duration. FNA smears showed bundles of spindle-shaped cells as well as
      plasmacytoid and stellate cells in sheets and dissociated forms. A few cells had
      nuclear grooves, and occasional cells showed intranuclear cytoplasmic inclusions.
      In May-Grunwald-Giemsa-stained smears, most of the cells had reddish cytoplasm.
      Red to purple, myxoid matrix was present as a scanty fibrillar substance and as
      globules surrounded by tumor cells vaguely reminiscent of adenoid cystic
      carcinoma. A cytodiagnosis of myoepithelioma was given and corroborated by
      immunocytochemical staining, which revealed a positive reaction for vimentin,
      smooth muscle actin and S-100 protein. Epithelial membrane antigen yielded a
      negative reaction except for a few plasmacytoid cells with weakly positive
      staining. Histopathology of the resected tumor and immunohistochemical staining
      confirmed the cytodiagnosis of myoepithelioma. CONCLUSION: FNA cytologic features
      together with immunocytochemical studies on smears can offer a preoperative
      diagnosis of myoepithelioma.

PMID- 15717757
TI  - Salivary duct carcinoma of the parotid gland: report of a rare case with a
      comparative study of aspiration cytology and histomorphology.
AB  - BACKGROUND: Salivary duct carcinomas affecting primarily the parotid gland are
      extremely rare (0.2-2% of all salivary gland tumors). These carcinomas are
      considered to be of high grade malignancy, with mortality in up to 70% of cases.
      They usually affect elderly males and less often young adults. Despite the fact
      that the histomorphologic characteristics of this tumor are always necessary for
      its classification, several authors have reported that the cytopathologic
      approach, using fine needle aspiration (FNA) cytology, can establish the final
      diagnosis. The aim of this paper is to present a rare case of salivary duct
      carcinoma of the parotid gland with no typical microscopic findings that was
      diagnosed by FNA cytology through a combination of techniques on biopsy material.
      CASE: A 56-year-old male presented with a right parotid mass measuring 6 cm in
      diameter. The mass appeared to expand subcutaneously and infiltrate the skin of
      the neck region. Biopsy material from both the mass and skin was obtained using
      FNA and processed with conventional, cell block and liquid-based cytology
      techniques. A core biopsy was also performed on the mass for histologic
      evaluation. CONCLUSION: The findings were consistent with a salivary duct
      carcinoma of the parotid gland and were confirmed by the histologic report. FNA
      cytology combined with such techniques as liquid-based cytology provides the
      potential for the final diagnosis. Liquid-based cytology can improve the cellular
      morphology of the material and allows immunocytochemistry and other diagnostic
      techniques. The application of such techniques is significantly restricted by
      conventional processing; thus, combining liquid-based cytology with other
      techniques expands the boundaries of cytology as a diagnostic test.

PMID- 15717759
TI  - Cytology of secondary vulvar Paget's disease of urothelial origin: a case report.
AB  - BACKGROUND: Primary cutaneous Paget's disease of the vulva is an intraepithelial
      adenocarcinoma most likely arising from a cutaneous stem cell with sweat gland
      epithelial differentiation or can be of sweat gland origin. Primary vulvar
      Paget's disease, however, can be mimicked by an internal noncutaneous neoplasm
      htat has extended to secondarily involve the vulva. Most commonly, this is due to
      an anal or rectal adenocarcinoma or a urothelial carcinoma. These malignancies
      may be detected in a vaginal or vulvar cytologic smear. CASE: An 81-year-old
      woman with a past history of urothelial carcinoma in situ of the bladder
      presented severalyears subsequent to treatment for bladder cancer with extensive
      vulvar and vaginal disease, clinically interpreted as primary vulvar Paget's
      disease involving the vagina. Vaginal cytology showed a high grade malignancy.
      The patient subsequently underwent radical (total deep) vulvectomy and vaginal
      excision. Subsequent investigation of her bladder showed recurrent urothelial
      carcinoma in situ with extensive spread to the vagina and vulva, simulating
      primary cutaneous vulvar Paget's disease. CONCLUSION: It is important to
      recognize secondary vulvar Paget's disease, although uncommon, because of the
      difference in therapy for primary and secondary vulvar Paget's disease. Certain
      cytologic characteristics in a vaginal or vulvar smear in a patient with
      suspected vulvar Paget's disease may aid in distinguishing them.

PMID- 15717760
TI  - Cytologic features of cribriform-morular variant of papillary carcinoma of the
      thyroid: a case report.
AB  - BACKGROUND: While the histology of cribriform-morular variant of papillary
      thyroid carcinoma has been well documented, its appearance on cytologic smears
      has rarely been described given the rarity of this tumor. CASE: A 28-year-old
      woman had a neck lump for an unspecified duration for which she sought medical
      attention. She was previously well, and there was no significant family history
      of illness. Fine needle aspiration of the thyroid mass disclosed columnar cells
      with fine to granular chromatin and nucleargrooves associated with papillary
      fragments and acinar formation. Occasional groups of epithelial cells forming
      morules, previously unreported on cytology, were present. An excision specimen of
      the left thyroid nodule revealed morphologic features of cribriform-morular
      variant of papillary carcinoma of the thyroid. CONCLUSION: A diagnosis of
      cribriform-morular variant of papillary carcinoma of the thyroid could be
      established on fine needle aspiration cytology, prompting exclusion of familial
      adenomatous polyposis and distinguishing it from other, more aggressive variants
      of thyroid carcinoma, such as columnar cell carcinoma.

PMID- 15717761
TI  - Cytology of papillary solid-cystic neoplasm of the pancreas presenting as an
      extrapancreatic mass: a case report.
AB  - BACKGROUND: Papillary solid cystic neoplasm (PSCN) of the pancreas is a tumor of
      low malignant potential and has an excellent prognosis. Although the cytologic
      features are well documented, it can pose a diagnostic problem when it presents
      as an extrapancreatic mass. CASE: A young woman presented with a retroperitoneal
      mass. Sonography and computed tomography (CT) showed a partially cystic mass
      touching the spleen and pancreas but distinct from both organs. The CT-guided
      aspiration cytologic diagnosis was paraganglioma. At surgery the mass was
      attached to the tail of the pancreas by a pedicle. The histologic diagnosis was
      PSCN of the pancreas. CONCLUSION: The cytologic findings in paraganglioma and
      PSCN may be strikingly similar, with both showing a perivascular pattern, acinar
      formations, cells with a moderate amount of ill-defined cytoplasm with red
      granularity on May-Grunwald Giemsa stain and a uniform chromatin pattern. This
      may be a source of diagnostic error, particularly in a patient presenting with a
      retroperitoneal, extrapancreatic mass.

PMID- 15717762
TI  - Cyopathologic and histologic features of biphasic pulmonary blastoma: a case
      report.
AB  - BACKGROUND: Biphasic pulmonary blastoma is a rare malignant neoplasm of debatable
      histogenesis. Although well described histologically, it is scarcely mentioned in
      the cytologic literature. CASE: A 78-year-old man reporting intermittent
      hemoptysis was admitted to the hospital. Chest radiography revealed a right-sided
      pulmonary mass. Cytologic examination of tumor specimens revealed 2 types of
      malignant cells. The smears were highly cellular, with a necrotic background. The
      stromal cells had predominantly round to ovoid or spindle-shaped nuclei and scant
      cytoplasm, and the nucleoli had slightly irregular borders with coarsely
      aggregated chromatin. The epithelial cells were arranged in sheets and glandular
      configurations. The cytoplasm of these cells was finely vacuolated or foamy, with
      indistinct cellular boundaries; eccentrically located nuclei were hyperchromatic
      and had irregularly shaped nucleoli. The cell block preparation showed a
      distinctly biphasic malignant tumor with the classic morphologic features of
      pulmonary blastoma. CONCLUSION: A preoperative diagnosis ofpulmonary blastoma is
      difficult to obtain by cytopathologic methods. A diagnosis of biphasic pulmonary
      blastoma should be considered whenever epithelial cells and a separate population
      of stromal cells are seen in a pulmonary exfoliative cytology specimen.

PMID- 15717763
TI  - Aspiration cytology of pulmonary small cell variant of poorly differentiated
      synovial sarcoma metastatic from the tongue: a case report.
AB  - BACKGROUND: Small cell variant ofpoorly differentiated synovial sarcoma (PDSS) is
      a great mimic of Ewing's sarcoma/primitive neuroectodermal tumor, with cytologic
      and immunohistochemical overlap. CASE: A 21-year-old male was admitted to our
      hospital because of a solitary pulmonary nodule that developed 22 months after
      resection of a tongue mass, small cell variant of PDSS. The nodule was biopsied
      via fluoroscopy-guided fine needle aspiration (FNA). At low power, the cytologic
      smears were highly cellular, consisting of a mixture of dispersed cells and loose
      or tight tissue fragments. The cells were characteristically uniform and
      monotonous, showing round to ovoid nuclei and scant cytoplasm. However, at high
      power, mild nuclear pleomorphism and frequent mitotic figures were noted. Blood
      vessels were often seen within the tumor cell aggregates. A diagnosis of
      metastatic sarcoma was rendered. Metastatectomy of the lung nodule was performed,
      and cytogenetic study showed t(X;18). CONCLUSION: A diagnosis of small cell
      variant of PDSS is difficult on routinely stained smears, but in the appropriate
      clinical setting, especially when a prior history of a primary tumor is
      available, a confident diagnosis can be established by FNA cytology.
      Immunohistochemistry and identification of SYT/SSX fusion transcript are useful
      for confirmation.

PMID- 15717764
TI  - Cytologic diagnosis of pancreatic tuberculosis in immunocompetent and
      immunocompromised patients: a report of 2 cases.
AB  - BACKGROUND: Pancreatic tuberculosis (PT) is a very rare occurrence in the setting
      of extrapulmonary tuberculosis. It usually occurs as a complication of miliary
      tuberculosis in immunodeficient individuals, particularly with HIV infections,
      but isolated involvement in an immunocompetent patient is extremely rare.
      Pancreatic involvement by tuberculosis in immunocompromised states, such as AIDS,
      and isolated involvement in immunocompetent patients require a high index of
      suspicion. Fine needle aspiration cytology under imaging guidance is highly
      conclusive. CASES: A patient presented with diabetes mellitus and a pancreatic
      mass clinically diagnosed as pancreatic carcinoma. A second patient, who was HIV
      seropositive, presented with generalized lymphadenopathy and a pancreatic mass,
      clinically diagnosed as lymphoma. These were conclusively diagnosed by fine
      needle aspiration cytology (FNAC) as PT under imaging guidance. After
      antituberculous therapy the first patient showed a dramatic improvement, whereas
      the second died; an autopsy was performed. Because of the atypical presentation
      of PT in immunocompromised and immunocompetent patients, FNAC can be used as a
      first-line diagnostic intervention. FNAC under imaging guidance is sensitive,
      specific, rapid and inexpensive. It resolves the diagnostic dilemma and thus
      avoids major surgery for a clinically diagnosed neoplasm.

PMID- 15717765
TI  - Metastatic minor salivary gland colloid carcinoma in the parotid region after
      parotidectomy for pleomorphic adenoma: a case report.
AB  - BACKGROUND: Primary colloid or mucinous carcinoma of the salivary glands is
      extremely rare. Only a few cases have been reported that originated in the minor
      salivary glands. an even more exceptional presentation is as a metastatic tumor
      in the parotid region subsequent to superficial parotidectomy for pleomorphic
      adenoma. The case presented here posed a diagnostic dilemma that could be
      resolved only after a thorough reevaluation of the previous cytologic and
      histologic material and detection of the occult primary tumor in the hypopharynx
      following an extensive clinical and radiologic workup. CASE: A 75-year-old female
      underwent fine needle aspiration of the left parotid and was diagnosed as having
      pleomorphic adenoma. A superficial parotidectomy removed the tumor completely,
      and the diagnosis was confirmed. Six months following the surgery, the patient
      developed an enlarged nodular mass in the ipsilateral parotid region, with fine
      needle aspiration showing colloid (mucinous) adenocarcinoma, which proved to be a
      metastatic colloid (mucinous) carcinoma on excisional biopsy. The clinical and
      radiologic workup in search of a primary lesion led to an occult tumor in the
      left hypopharyngeal mucosa. CONCLUSION: Unusual presentations of rare tumors can
      cause considerable diagnostic difficulties to both the clinician and
      cytopathologist. Awareness of these rarities is important to ensure the best
      patient care and to avoid unnecessary investigative and therapeutic procedures.

PMID- 15717767
TI  - Cytology of brain metastasis of yolk sac tumor.

PMID- 15717769
TI  - Squash smear findings of eosinophilic granular bodies in pilocytic astrocytoma.

PMID- 15717766
TI  - Detection of growth hormone-releasing hormone in cytologic specimens of primary
      breast carcinoma.

PMID- 15717768
TI  - Acid-fast staining patterns and their correlation with HIV positivity.

PMID- 15717770
TI  - Fine needle aspiration diagnosis of congenital langerhans cell histiocytosis of
      the lymph nodes with isolated skin involvement.

PMID- 15717771
TI  - Child welfare reform in the United States: findings from a local agency survey.
AB  - Efforts to improve the public welfare and child welfare system sparked an
      unprecedented amount of federal legislation in the 1990s, including the Adoption
      and Safe Families Act of 1997 (ASFA), the Multiethnic Placement Act of 1994 and
      Interethnic Adoption Provisions of 1996 (MEPA-IEP), and welfare reform. Such
      reforms allow an unprecedented degree of flexibility, but little is known about
      their implementation. Researchers administered the Local Agency Survey to the
      first national probability sample of public child welfare agencies from 1999 to
      2000. Findings indicate that ASFA has had the most effect on child welfare
      service delivery. Welfare reform has had less effect, and MEPA-IEP seems to have
      had little effect at all.

PMID- 15717773
TI  - Reunification of child and animal welfare agencies: cross-reporting of abuse in
      Wellington County, Ontario.
AB  - Institutional change has resulted in the separation of organizations for the
      protection of animals and children. This project reunites two organizations to
      examine associations between human violence and animal cruelty. For 12 months,
      Family and Children's Services (FCS) investigators and Humane Society (HS)
      investigators in Wellington County, Canada, completed checklists to examine
      connections between forms of violence. FCS workers found some cause for concern
      in 20% of 1,485 homes with an animal companion. HS workers completed 247
      checklists, resulting in 10 referrals to FCS. The first study of its kind, this
      project details the findings of cross-reporting in Wellington County and offers
      suggestions for future replication.

PMID- 15717772
TI  - Vstreet.com: a web-based community for at-risk teens.
AB  - Most teens leaving the care of an agency are woefully unprepared and unsupported.
      Current approaches to aftercare are expensive and difficult to implement. This
      study evaluated a prototype version of Vstreet.com, an innovative website for at
      risk youth designed to teach lifeskills and build community. Findings from a
      sample of youth in the Job Corps showed that the website was highly effective in
      increasing their knowledge of apartment hunting skills, feelings of peer social
      support, and intentions of staying in touch with their agency.

PMID- 15717774
TI  - Obstacles to employment among mothers of children in foster care.
AB  - This article reports on a study of obstacles to employment among mothers with
      children in foster care. The study relies on standardized measures, has a cross
      sectional design, and includes a sample of 158 mothers. The analysis shows a high
      prevalence of obstacles; identifies three co-occurring obstacles, each involving
      substance abuse, that are related to a low probability of employment (p < or =
      .05); and reveals that employment and access to transportation are related to
      higher income relative to mothers' needs (p < or = .05).

PMID- 15717775
TI  - Determination of geno- and cytotoxicity of groundwater and sediments using the
      recombinant SWITCH test.
AB  - The recombinant Salmonella typhimurium TA1535 strain carrying the SWITCH plasmid
      (combined construct of the SOS-Lux plasmid pPLS-1 and the LAC-Fluoro plasmid
      pGFPuv: pSWITCH) was treated with control substances for genotoxic (2
      aminoanthracene) and cytotoxic (aureomycin) potency as well as with 18
      environmental samples (groundwater, river water, sediments) provided at the
      SENSPOL Technical Meeting on Problems Related to Diffuse Pollution Sources
      (Characterization of Sediment, Dredged Material, and Groundwater) organized by
      the Federal Institute of Hydrology in Koblenz, Germany, during late October 2003.
      For metabolic activation the samples were treated with S9 mix (5% S9 fraction in
      cofactor mix, Aroclor 1254-induced rat liver microsomes, Moltox Inc., Mol,
      Belgium). Simultaneously determined cytotoxicity and genotoxicity data were
      derived through the Multilabel Counter 1420 Victor (PerkinElmer, Boston, MA,
      USA), by sequential measurement of luminescence, absorbance, and fluorescence.
      The newly designed SWITCH test, as it was applied at the Koblenz meeting,
      displays a comparable sensitivity for test samples with known cyto- and genotoxic
      potential. Groundwater samples from the wells at the former gas plant site Kiel
      Canal and the agricultural area at Niederwerth expressed neither genotoxic nor
      cytotoxic responses of the bacteria for both metabolic conditions (+/-S9). Spiked
      groundwater samples from the Niederwerth well BW1 and the Urmitz well U12 located
      on the river Rhine were identified to be positive in terms of genotoxicity for
      the direct and the metabolic approach. Samples from the lake Tiefer See in the
      city of Potsdam showed a reduction of GFPuv expression as an indication for
      cytotoxicity, while luminescence output of incubated bacteria remained
      unaffected. This reflects the well-known presence of contaminations (especially
      cyanides) in the lake sediment as well as in the acetonic extract. The results
      obtained at the SENSPOL Technical Meeting show the SWITCH test to be of major
      relevance not only for the analysis of chemicals under laboratory conditions but
      also for environmental samples polluted by diffuse industrial sources.

PMID- 15717776
TI  - The Elbe flood in August 2002--organic contaminants in sediment samples taken
      after the flood event.
AB  - In the course of this study 37 sediment samples were analyzed. They were taken
      after the flooding in September 2002 along the Elbe and at the mouths of its
      major tributaries. The sampling program covered the entire river stretch that was
      affected by the floods, from Obristvi (Czech Republic) to the Elbe estuary (North
      Sea) on the German coast. Analyses were performed for dioxins, nonylphenols,
      nonylphenol ethoxylates, bisphenol A, DEHP, musk fragrances, polybrominated
      diphenylethers, chloroalkylphosphates, organochlorine compounds, PAH, and
      organotin compounds. The results show that only a few weeks after the flood,
      contaminant concentrations in solid matter were comparable to those prevailing
      beforehand. Significant sources of contaminant input proved to be the tributaries
      Vltava (Moldau), Bilina (both in the Czech Republic), and the Mulde (Germany), as
      well as industrial and municipal sewage treatment works (STW) located along the
      Elbe. Further point sources are to be found in still water zones such as harbors
      and abandoned channels. These sources are activated when erosive action stirs up
      older sediments. Statistical analyses of the congener distribution of the dioxins
      provided evidence on the sources of these contaminants and freight levels in
      different river sections. The chemical analyses were complemented by results of
      ecotoxicological investigations with two sediment organisms (Chironomus riparius
      and Potamopyrgus antipodarum).

PMID- 15717777
TI  - Linking sediment chemical and biological guidelines for characterization of
      dredged material.
AB  - Dredged material management in Spain and possible options for the different
      categories is discussed according to chemical sediment quality guidelines. Also
      an approach using an integrated assessment that includes biological end points as
      part of a tiered testing schema is discussed for future implementation in Spanish
      recommendations. To establish the feasibility of using both kinds of guidelines,
      an example of the utility and validity of the approach that links both chemical
      and biological guidelines proposed for the management of dredged material
      characterization processes data from a particular case study associated with a
      port in the north of Spain are discussed. The use of both kinds of methodologies,
      together with the necessity of assessing the bioavailability of some
      contaminants, has been shown as a powerful tool for the best selection of
      different disposal options of dredged material in the case study described.

PMID- 15717778
TI  - Distribution of selected heavy metals in sediments of the Agueda river (Central
      Portugal).
AB  - The state of river water deterioration in the Agueda hydrographic basin, mostly
      in the western part, partly reflects the high rate of housing and industrial
      development in this area in recent years. The streams have acted as a sink for
      organic and inorganic loads from several origins: domestic and industrial sewage
      and agricultural waste. The contents of the heavy metals Cr, Cd, Ni, Cu, Pb, and
      Zn were studied by sequential chemical extraction of the principal geochemical
      phases of streambed sediments, in the <63 microm fraction, in order to assess
      their potential availability to the environment, investigating the metal
      concentrations, assemblages, and trends. The granulometric and mineralogical
      characteristics of this sediment fraction were also studied. This study revealed
      clear pollution by Cr, Cd, Ni, Cu, Zn, and Pb, as a result from both natural and
      anthropogenic origins. The chemical transport of metals appears to be essentially
      by the following geochemical phases, in decreasing order of significance:
      (exchangeable + carbonates) >> (organics) >> (Mn and Fe oxides and hydroxides).
      The (exchangeable + carbonate) phase plays an important part in the fixation of
      Cu, Ni, Zn, and Cd. The organic phase is important in the fixation of Cr, Pb, and
      also Cu and Ni. Analyzing the metal contents in the residual fraction, we
      conclude that Zn and Cd are the most mobile, and Cr and Pb are less mobile than
      Cu and Ni. The proximity of the pollutant sources and the timing of the influx of
      contaminated material control the distribution of the contaminant-related
      sediments locally and on the network scale.

PMID- 15717779
TI  - Seasonal variation of surface sediments composition in Mondego River estuary.
AB  - Concentrations of major (Al, Si, Ca, Mg, Fe), minor (Mn), and trace elements (Zn,
      Pb, Cr, Cu, Ag, Cd, Hg) and organochlorine compounds (PCB congeners, pp'DDT, and
      metabolites) were determined in 24 samples of surface sediments (0-5 cm)
      collected along the Mondego River estuary in two periods: February and August
      2003. All sediment samples showed low levels of contamination reflecting the weak
      industrialization of the region. Higher incorporation of elements (Mg, Fe, Zn,
      Cr, Cu, Cd, Hg) and DDT was registered in muds deposited in the inner part of the
      south channel. Sediments of the rest of the estuary are coarser (mean Si/Al ratio
      around 11) and showed much lower Me/Al ratios. Concentrations of Mn, Pb, Ag, and
      PCB showed no geographical distribution tendency. However, Pb, Cu, Ag, Zn, Cd
      ratios to Al and PCB concentrations were higher in coarser sediments collected in
      February than in August. In addition, the lower chlorinated CBs (tri + tetra-CB)
      showed a higher proportion in sediments collected in February, due to its higher
      mobility and low contamination in the area. The results obtained in this river
      dominated estuarine system, with weak local contamination sources, indicate that
      chemical composition of surface sediments reflects the diffuse source of
      contaminants associated with the rainy season.

PMID- 15717780
TI  - Assessing toxicities of hydrophobic organic pollutants in Huaihe River by using
      two types of sampling.
AB  - Hydrophobic organic pollutants in water from the Huaihe River were extracted by
      solid phase extraction and sequestered by semipermeable membrane device (SPMD),
      and those in sediments were extracted by organic solvent. Combined with chemical
      analysis, Lumistox test and ethoxyresorfin O-deethylase (EROD) assay were carried
      out for assessing the acute toxicities and the Ah-receptor-related toxic effects
      of the trace hydrophobic organic pollutants in this aquatic environment. The
      acute toxicants in water and sediment of the Huaihe River included substituted
      benzenes and pesticides, mainly 2,4,6-trichlorophenol, atrazine,
      hexachlorobenzene, and nitrobenzenes as well as persistent EROD inducers or Ah
      agonists, including PAHs and PCBs, were determined. The highest acute toxicant
      concentration occurred at the center of the river (H3), while highest chronic
      toxicants occurred at upstream (H1). At downstream (H4), the EROD inducers in
      sediment depicted more persistency. The results also showed that the sampling
      procedures for waters have significant influences on the results of bioassays.
      Bioassay for acute toxicants in water using SPE was unable to obtain important
      information. However, bioassays for sediment extracts and SPMD concentrates
      showed similar pattern of toxic variation among different locations.

PMID- 15717781
TI  - Speciation of volatile aromatic and chlorinated hydrocarbons in an urban
      atmosphere using TCT-GC/MS.
AB  - Several aromatic and chlorinated volatile hydrocarbons (VOCs) were measured in
      Vitoria-Gasteiz City (Spain) throughout the years 1999 and 2002 in order to find
      out the concentration of these pollutants in urban air. These VOCs were retained
      in Tenax TA, subsequently desorpted by using a thermal desorption cold trap
      injector (TCT), and thereafter analyzed by gas chromatography/mass spectrometry
      (GC/MS). This analytical methodology permits the determination of 42 VOCs at very
      low concentrations, although only 32 of them were found in the urban air of the
      city (ranging from 205.51 to 0.01 microg m(-3)), with high reproducibility (%RSD
      lower than 10%). Twenty-four-hour samples were taken each sampling day to
      ascertain their total daily concentration, and rigorous quality controls were
      carried out to check the representativeness of sampling. Results of this
      exhaustive study show that toluene (T), xylenes (X), ethylbenzene (E), and
      benzene (B) were, respectively, the most abundant of these VOCs in the urban area
      during that period. The total concentration of BTEX represented, on average, more
      than 72.6% of the VOC total concentration, with the highest concentrations being
      reached in autumn, except for benzene and derived compounds (in winter). Benzene
      was the minority BTEX pollutant, its yearly mean concentration being less than
      the maximum established by the European Directive 2000/69/CE (5 microg m(-3)).

PMID- 15717782
TI  - Assessment of apoptosis in thymocytes and splenocytes from mice exposed to
      arsenate in drinking water: cytotoxic effects of arsenate on the cells in vitro.
AB  - This study provides an assessment of the level of apoptosis in thymocytes and
      splenocytes from mice exposed to arsenate in drinking water. To simulate the
      naturally occurring exposure conditions of humans, the animals were exposed to
      arsenate at the concentrations of 0.5, 5, and 50 mgAs/L. TUNEL method for
      staining of thymocytes and splenocytes isolated from the mice after 8 and 12
      weeks revealed increased percentage of apoptotic cells in the exposed groups.
      Although statistically significant increases were observed only for the highest
      concentration of arsenate, the increases showed linear trend as a function of
      arsenate concentration in drinking water. In vitro experiments performed on
      isolated cells incubated for 24 hours with arsenate at 6.7-2000 microM showed
      very similar concentration-viability relationships for both cell populations
      (IC50 was 442+/-15 microM and 427+/-18 microM for thymocytes and splenocytes,
      respectively). Arsenate induced a concentration-dependent increase in the
      percentage of the cells undergoing apoptosis. At higher concentrations, apoptosis
      was the predominant mode of cell death. It can be speculated that proapoptotic
      effects of arsenate as observed in our in vivo study may contribute to some
      immunotoxic symptoms observed in people chronically exposed to arsenic in
      drinking water.

PMID- 15717783
TI  - Evaluation of extraction procedures for removing lead from contaminated soil.
AB  - Soil extraction of lead contaminated soil collected from sites near an abandoned
      battery recycling and secondary lead-smelting factory was investigated for
      potential use in decontaminating soil at the sites. A fractionation study was
      conducted to elucidate soil retention mechanism for Pb at the site. Three soil
      pits were selected from an area surrounding the factory based on level of Pb
      contamination. Soil samples were collected from each pit in two layers: surface
      soil and subsoil (0-15 cm and 15-30 cm). Soil physical analysis showed that the
      soil texture was sandy loam and sandy clay loam with clay content between 11-21%.
      Soil pH was strongly acid to moderately acid (pH 4.8-5.9). Pb levels in the
      surface soil were 1620 and 153 mg kg(-1) (air-dried basis) respectively for
      heavily and slightly contaminated soil. A reference soil site contained 15 mg kg(
      1) of Pb. Partitioning studies indicated that more than 90% of total Pb in the
      soil existed in three primary fractions: exchangeable, carbonate, and Fe-Mn
      oxide. This suggested that Pb sources entering the soil from the Pb factory
      remained in relatively weakly bound forms, which are mobile and have potentially
      biological availability. Mobility of Pb as in the soil assessed by mobility
      factor (MF) was as high as 75% indicating a high potential of Pb remobilization.
      Due to high mobility, the Pb would be amendable to remediation or removal by soil
      extraction procedures. To determine if such weekly bound Pb could be easily
      removed, both soil washing (ex situ) and soil flushing (in situ) techniques were
      evaluated for potential Pb remediation procedure. Particle size separation of
      soil into coarse (2.0-0.25 mm), medium (0.25-0.15 mm), and fine size (<0.15 mm)
      was conducted before initiating soil washing for comparing Pb removal efficiency
      in these fractions with the indigenous soil fraction. Using EDTA (2:1 mole to Pb)
      as a washing solution up to 85-95% of Pb was removed under the optimum conditions
      (retention time = 60 min), and liquid to solid ratio (L/S) at 5:1 for coarse
      fraction and 10:1 for smaller fraction. Pb could be removed from contaminated
      soil using EDTA extraction; however, the efficiency was higher in the coarse
      texture soil fraction. As a result particle size separation is recommended before
      application of the soil washing procedure. For smaller soil particle size
      fraction a series of extraction was needed for obtaining an adequate extraction
      efficiency. Three solvents tested as flushing solution showed 85, 84, and 74% of
      Pb was removed by EDTA (2:1 mole to Pb), 1M HNO3, and 0.2 M ammonium citrate,
      respectively after flushing with 20 pore volumes. The capacity of the three
      flushing solutions to remove Pb from the contaminated soil were ranked in the
      order: EDTA approximately 1 M HNO3 > 0.2 N ammonium citrate. However, in highly
      contaminated soil all solvent extract required several Pb leaching cycles. The
      flushing process using 1 M HNO3 increased soil acidity to extreme acid conditions
      (pH 2.0) resulting in adverse effects to physicochemical properties of the
      treated soil. In general, results showed three factors influenced Pb removal by
      the extraction techniques: (i) initial Pb concentrations, (ii) Pb partitioning
      within soil, and (iii) particle size of soil matrix.

PMID- 15717784
TI  - Microbial ecology of bulking and foaming activated sludge treating tannery
      wastewater.
AB  - This study involves a comprehensive survey of the microbial ecology of the
      activated sludge process treating tannery wastewater, emphasizing evaluation
      during periods of bulking and foaming. The survey also includes a detailed
      characterization of process influent and effluent. Observations always associate
      bulking with significant increase in protozoa species and rotifers, but decrease
      or disappearance of nematodes. Activated sludge sustained under normal conditions
      with a sludge volume index lower than 80 ml g(-1), exhibits all the properties of
      a compact and healthy zoogleal floc structure. Three types of filamentous
      bacteria prevail in the microscopic examinations. Two of the filamentous
      bacteria, Microthrix parvicella and Nostocoida limicola II, always appear as
      components of the floc structure under normal conditions and abundant or even
      excessive levels. The study identifies Gordona spp. as the main microorganism
      responsible for bulking and foaming, which starts by a Gordona contamination
      process inside the floc, later branching out and extending through adjacent
      flocs. When completed, this process increases sludge volume index values to over
      200 ml g(-1). Microscopic examinations indicate significant morphological
      differences between filamentous microorganisms observed in this study and
      reported in the literature mostly for domestic sewage treatment.

PMID- 15717785
TI  - Treatment of dyeing wastewater by TiO2/H2O2/UV process: experimental design
      approach for evaluating total organic carbon (TOC) removal efficiency.
AB  - Optimal operating conditions in order to treat dyeing wastewater were
      investigated by using the factorial design and responses surface methodology
      (RSM). The experiment was statistically designed and carried out according to a
      22 full factorial design with four factorial points, three center points, and
      four axial points. Then, the linear and nonlinear regression was applied on the
      data by using SAS package software. The independent variables were TiO2 dosage,
      H2O2 concentration and total organic carbon (TOC) removal efficiency of dyeing
      wastewater was dependent variable. From the factorial design and responses
      surface methodology (RSM), maximum removal efficiency (85%) of dyeing wastewater
      was obtained at TiO2 dosage (1.82 gL(-1)), H2O2 concentration (980 mgL(-1)) for
      oxidation reaction (20 min).

PMID- 15717786
TI  - Effects of several applications of digested sewage sludge on soil and plants.
AB  - Sewage sludge production has significantly increased during the last years in
      European Union (EU) countries, being primarily used for agricultural purposes. In
      this study, digested sewage sludge was applied to greenhouse soil over a three
      year period (2001--2003), with three sludge treatments in the first two years (2,
      4, and 6 kg m(-2)) and three more applications using a greater quantity in the
      last year (6, 8, and 10 kg m(-2)). The effects of sewage sludge application on
      soil and on a leafy crop (Lactuca sativa L.) were studied. Mineral elements,
      organic matter, pH, and heavy metals were measured in soil and plant tissues.
      Pathogen and indicator microorganism dynamics in soil were also determined after
      each sludge application. Results showed that sewage sludge applications increased
      organic matter, P, and N Ca content in soil. Furthermore, Zn, Pb, Ni, and Cu
      content increased in soils, primarily after high doses of sludge. The highest
      yield value was obtained in the second-year harvest, since the last sludge
      application did not increase yield. Fecal coliform numbers decreased
      significantly one month after sludge application. However, total coliforms,
      Clostridium sulphite-reducers and Salmonella, were present in soils three months
      after sludge application.

PMID- 15717787
TI  - Electrochemical degradation of microcystin-LR.
AB  - Microcystin-LR present in drinking water sources poses a considerable threat to
      human health. Conventional oxidation treatment systems, such as photocatalysis
      and ferrate oxidation, demonstrated the formation of by-products detectable in
      the treated microcystin-LR solution. This study investigated an electrochemical
      approach for microcystin-LR oxidation. The oxidation rate of microcystin-LR
      increased with the current; the oxidation rate was 0.219 min(-1) and the half
      life was 2.5 min at an applied current of 100 mA to treat 1.0 mgL(-1) of
      microcystin-LR solution. These results were almost the same as those obtained
      from the photocatalytic oxidation of a 0.055 mgL(-1) microcystin-LR solution. The
      average instantaneous current efficiency of currents from 30 to 150 mA was
      greatest at 100 mA because both the current and the microcystin-LR concentration
      limited the oxidation rate. In addition, no by-products were detected by HPLC,
      which suggests that the microcystin-LR can be decomposed completely by the
      indirect oxidation of the hydroxyl radicals formed during electrochemical
      treatment. We demonstrated that the electrochemical oxidation is a promising
      approach for the complete oxidation of microcystin-LR.

PMID- 15717788
TI  - Variations in hospital waste quantities and generation rates.
AB  - The relationship between public health and improper collection, handling, and
      disposal of solid wastes in general, and hospital wastes in particular, is quite
      clear. Hazardous and nonhazardous wastes generated from different divisions of
      two of the largest public hospitals (capacity of approximately 400 beds each) in
      Kuwait were quantified and generation rates were determined. The generation rates
      were related to some important factors such as the number of patients, number of
      beds, and the type of activity conducted in different sections of the hospitals.
      The relationship between the waste generation rate and the number of patients was
      more applicable than that expressed in terms of the number of beds. The rates
      observed were in the range of 4.89 to 5.4 kg/patient/day, which corresponds to
      3.65 to 3.97 kg/bed/day, respectively. These generation rates were comparable
      with those reported in the literature for similar hospitals. Minimal waste
      quantities were collected in the weekends. The study indicated that the hospitals
      surveyed provide some segregation of hazardous and nonhazardous wastes. Hazardous
      wastes contributed about 53% of the total quantity of wastes generated at the
      hospitals.

PMID- 15717789
TI  - Separation of gallium and arsenic in wafer grinding extraction solution using a
      supported liquid membrane that contains PC88A as a carrier.
AB  - Wafer grinding extraction solution was passed through a supported liquid membrane
      (SLM) that contained PC88A (2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester)
      as a carrier, to separate gallium from arsenic by selective permeation. The SLM
      separation process was conducted under various conditions. The kind of membrane
      supporter, the pH of the feed, the feed concentration, and the HCl content in the
      strip governed the concentration of gallium and arsenic in the strip phase. The
      conditions determined as optimal in the laboratory test were used to perform the
      pilot test. Well separation between gallium and arsenic was performed in both
      laboratory and pilot tests. Hydrophobic membrane polytetrafluoroethylene (PTFE)
      with 0.2 microm pores was the best of three membrane supporters. The most
      efficient separation was obtained using an acidic feed (pH at 1.8) with 1000 ppm
      gallium. Over a 12-h period of stripping, the striped Ga concentration increased
      with the HCl concentration from 0.5 to 2.0 M and then leveled off. The recovery
      rate in the pilot test exceeded that on the laboratory scale because the membrane
      area was greater. The pilot test yielded a high recovery percentage of gallium
      (at 91%) and a low recovery of arsenic (merely 1.3 ppm) in the strip over 72 h.

PMID- 15717790
TI  - A sacred duty.

PMID- 15717791
TI  - Expanding the human spirit.

PMID- 15717792
TI  - Lightwave of the future.

PMID- 15717793
TI  - This bed is just right.

PMID- 15717794
TI  - Measuring the right angle.

PMID- 15717795
TI  - Finding the proper brace.

PMID- 15717796
TI  - Capital needs.

PMID- 15717798
TI  - Congressional top ten list.

PMID- 15717797
TI  - Discharge or episode of care?

PMID- 15717799
TI  - [Liver transplantation finally available also for our patients with chronic
      hepatitis B virus infection].

PMID- 15717800
TI  - [Liver transplantation for chronic hepatitis B].

PMID- 15717801
TI  - [The activation of haemostasis during radiofrequency catheter ablation].
AB  - The aim of the study was to investigate chosen haemostasis activation markers
      during electrophysiologic study (EPS) with consequent radiofrequency catheter
      ablation (RFA). Sixty-three patients were studied prospectively. Indications for
      EPS and RFA were supraventricular tachycardias with the arrhythmogenic substrate
      located in the right atrium. Blood samples were drawn 24 hours before the
      procedure (T -1), at the beginning of the procedure (T0), at the end of EPS (T1),
      30 minutes after completion of RFA (T2), and 24 hours after the procedure (T3).
      To study coagulation, fibrinolytic and platelet activation were measured
      concentrations of thrombin-antithrombin III (TAT), D-dimers (DD), platelet count
      and parameters, and circulating platelet aggregates (CPAi). During the EPS and
      RFA, TAT levels increased from the baseline 5.03 +/- 2.53 microg/l (T -1) to
      12.90 +/- 12.83 microg/l at T0 (p < 0.001) to 36.07 +/- 15.59 microg/l at T1 (p <
      0.001) and decreased to 28.85 +/- 13.14 microg/l at T2 (p < 0.001). Levels of DD
      increased from 0.30 +/- 0.20 mg/l at T0 to 0.44 +/- 0.25 mg/l at T1 (p < 0.001)
      and to 0.87 +/- 0.74 mg/l at T2 (p < 0.001). The number of platelets was
      significantly decreased (-13.7%) before and during the procedure (T -1 vs. T3; p
      < 0.001). Marked platelet activation (CPAi 0.62 +/- 0.32) was observed before the
      procedure opposite to the physiological values (CPAi 1.0 +/- 0.1), without
      changes during the procedure (CPAi at T2 0.69 +/- 0.23). Our results confirmed
      activation of several haemostasis parameters during EPS and RFA, and support
      eligibility of the antithrombotic prevention in patients indicated for EPS and
      RFA.

PMID- 15717802
TI  - [Relation between diabetes compensation, albuminuria and biochemical parameters
      and the results of stress myocardial SPECT in asymptomatic type 2 diabetics].
AB  - The patients with diabetes mellitus and another risk factors have significantly
      higher risk to suffer from ischemic heart disease. Myocardial stress SPECT
      represents the examination which correlates very well with the results of
      selective coronary angiography even in asymptomatic diabetic patients. The aim of
      our study was to evaluate the relation of SPECT result to diabetes compensation,
      presence of micro/macroalbuminuria, blood level of fibrinogen, CRP, homocysteine
      and uric acid. Out of 126 diabetic 2. type abnormal SPECT has been found in 33
      (26%). Fasting blood sugar (9.3 +/- 1.4 mmol/l in patients with abnormal SPECT
      vs. 9.7 +/- 1.9 mmol/l in the other diabetics, n.s.) and HbA1c (7.5 +/- 1.3% vs.
      7.5 +/- 1.3%, n.s.) are not significantly different in the patients with abnormal
      SPECT to the other diabetics without this finding. Micro/macroalbuminuria was
      significantly more frequently seen in patients with abnormal SPECT (60% of
      patients with abnormal SPECT and 29% in the rest of diabetics, p = 0.01).
      Fibrinogen was significantly more elevated in diabetics with abnormal SPECT (3.76
      +/- 0.5 g/l in the group with abnormal SPECT vs. 3.23 +/- 0.43 g/l, p = 0.0003).
      In the diabetics with abnormal SPECT we have found significantly higher CRP (3.84
      +/- 1.51 mg/l vs. 2.79 +/- 1.13 mg/l, p = 0.024) and homocysteine (13.78 +/- 3.26
      micromol/l vs. 10.98 +/- 2.33 micromol/l, p = 0.006). Uric acid level was not
      significantly different in the group of diabetics with abnormal SPECT to the rest
      of the patients (361 +/- 64 micromol/l in abnormal SPECT vs. 353 +/- 51
      micromol/l, n.s.). When we analyse our results we have found that abnormal SPECT
      is rarely discovered in the asymptomatic 2nd type diabetics with the combination
      of negative micro/macroalbuminuria and fibrinogen level below 3.5 g/l.

PMID- 15717803
TI  - [Factors participating in development of bleeding varices in portal hypertension.
      Part II: Possible impact of kidney damage and malnutrition, mortality].
AB  - An acute bleeding from oesophageal varices as a result of portal hypertension is
      a frequent and serious complication of liver cirrhosis. The development of
      oesophageal varices and their rupture depends on the portal pressure. However, a
      range of other factors can contribute to a development of bleeding and its
      negative prognosis. A sample of 46 patients admitted for the acute bleeding has
      been compared to 48 cirrhosis patients hospitalised for other conditions in this
      work. There were significantly higher levels of nitrogenous matters in bleeding
      patients (urea 14.1 mmol/l vs. 7.78 mmol/l, p < 0.01, creatinine 129.8 micromol/l
      vs. 106.04 micromol/l, p = 0.09). Perhaps it can't be said that impaired renal
      functions alone increase the risk of bleeding. From this point of view they could
      rather be seen as definite prognostic markers of the degree of portal
      hypertension. Moreover, there was a decreased level of total proteins in bleeding
      patients (60.7 g/l vs. 69.9 g/l, p < 0.01) at a mild nonsignificant decrease of
      albumin (26.64 g/l vs. 28.51 g/l). Cirrhotic patients are known to suffer from
      malnutrition and there is a possibility that malnutrition can contribute to
      development of bleeding. A prognostic marker of mortality was a considerable
      impairment of liver function (bilirubin 97.4 micromol/l vs. 57.4 micromol/l; p =
      0.1 and prolonged prothrombin time 1.99 INR vs. 1.56 INR; p = 0.09) and impaired
      kidney function (creatinine 166.7 micromol/l vs. 114.9 micromol/l, p = 0.09).
      Therefore a care of a good renal function must be a part of the complex care of
      bleeding patients.

PMID- 15717804
TI  - [Liver transplantation for hepatitis B].
AB  - Up to now the outcomes of liver transplantation in patients with chronic viral
      hepatitis B have not been very good because the recurrence of viral hepatitis in
      the graft has been high and resulted in a high early graft failure of liver
      transplant recipients. However, the administration of a combined therapy with
      lamivudine and hyperimmune anti-HBs globulin has led to a marked improvement in
      transplantation results and an increase in the number of liver transplantations
      for this indication. Four men (aged 47 to 55 years) underwent liver
      transplantation for cirrhosis, caused by chronic viral hepatitis B, at our
      centre. All were HBsAg carriers. They were our first patients who received
      therapy with the combined immunoprophylactic regimen of lamivudine and
      hyperimmune anti-HBs globulin. HBV DNA negativity was achieved in all patients
      prior to transplantation; three of them were pretreated with lamivudine. At 4 to
      17 months of follow-up, sustained suppression of HBV replication (HBV DNA
      negativity) was maintained in all four patients. No complications associated with
      this treatment were observed and no emergence of resistant mutants was detected.
      The combined therapy for chronic viral hepatitis B administered to liver
      transplant recipients at our centre showed very good outcomes. However, the
      development of resistant mutants during this therapy poses a problem, which may
      hopefully be overcome with the use of new antivirotics, such as adefovir or
      tenofovir.

PMID- 15717805
TI  - [Seroprevalence of Helicobacter pylori in rheumatoid arthritis and its
      relationship to pharmacotherapy].
AB  - GOAL: To find out a serology prevalence of Helicobacter pylori (Hp) infection in
      patients suffering from rheumatoid arthritis (RA) and to investigate its
      relationship to pharmacotherapy modes. METHOD: To determine Hp IgG class and IgA
      class antibodies by ELISA method in hospitalised patients with active RA
      according to ACR criteria (1987). RESULTS: 137 patients with RA were examined--20
      men, 117 women, an average age was 54.6 +/- 13.1, an average length of RA in
      these patients was 12.46 +/- 9.75, positive RF/LFT had 88% of patients. Hp ELISA
      IgG antibodies were confirmed in 57% (78/137) of patients with RA, Hp ELISA IgA
      antibodies were confirmed in 60% of examined patients (82/137), and IgG + IgA
      antibodies simultaneously were found in 51% (70/137) of examined patients. A
      comparison of basic demographic data, specific parameters of the disease, and
      clinical signs has not confirmed any differences between groups of Hp positive
      and Hp negative patients. Patients with both types of Hp antibodies (IgG + IgA)
      had more frequent signs of RA in other places than joints (p = 0.046). RA
      patients with anti-Hp IgG antibodies more frequently used anticoagulation drugs
      (p = 0.029) while patients with anti-Hp IgA antibodies more frequently used
      methotrexate (p = 0.01). CONCLUSIONS: Results point out more frequent incidence
      of Hp IgA antibodies in RA patients treated with methotrexate and more frequent
      incidence of both IgG and IgA antibodies in patients with RA signs in other
      places than joints.

PMID- 15717806
TI  - [Activated factor XII in patients with hyperglycaemia and dyslipidaemia].
AB  - BACKGROUND: Increased plasma levels of activated factor FXII (FXIIa) are
      associated with increased risk of atherosclerosis and coronary heart disease.
      There are increased levels of FXIIa in patients with dyslipidaemia and also
      elevated levels of FXIIa have been reported in patients with diabetes mellitus.
      No studies were reported whether FXIIa correlates rather with plasma glucose
      levels or with other metabolic markers like hypertriacylglycerolemia. METHODS: We
      measured plasma FXIIa levels, triacylglycerols, uric acid and glucose in a group
      of 158 hyperglycaemic patients with P-glucose more than 8 mmol/l and variable
      serum lipid parameters [cholesterol, triacylglycerols, HDL-cholesterol, LDL
      cholesterol, lipoprotein (a), apolipoprotein AI, apolipoprotein B] in a group of
      55 patients of lipid clinic on hypolipidaemic treatment (statins, fibrates).
      RESULTS AND CONCLUSION: The comparison of FXIIa with the age in the group of
      hyperglycaemic patients has shown that the number of patients with FXIIa more
      than 2.5 microg/l is growing with increasing age. Low concentration of FXIIa was
      observed in the youngest age group (10-30 years), where all values are within the
      reference ranges. We proved positive correlation between plasma FXIIa levels and
      age, triacylglycerols, uric acid. No correlation was found between plasma FXIIa
      and glucose in both groups.

PMID- 15717807
TI  - [A relationship between dehydroepiandrosterone sulphate and insulin resistance in
      obese men and women].
AB  - The aim of our study was to investigate if there is any significant relationship
      between adrenal steroid hormone dehydroepiandrosterone-sulphate (DHEAS) and
      insulin resistance, as there are some previous signs in the literature suggesting
      such relationship but the results are not conclusive. METHODS: In our study
      participated 50 obese women and 20 obese men both with BMI over 27 kg/m2. Insulin
      resistance was calculated using HOMA insulin resistance index (HOMA-IR) that is
      based on fasting glycaemia and basal insulin levels. RESULTS: The negative
      correlation between DHEAS and HOMA-IR was found in the whole group of obese women
      but close behind statistical significance (r = -0.27, p = 0.055). But the group
      of obese women does not seem to be homogenous in correlation between DHEAS and
      insulin resistance. The significant negative correlation between DHEAS and
      insulin resistance was found in the subgroup (n = 21) of obese type 2 diabetic
      women (r = -0.55, p = 0.01) but no correlation was found in the subgroup (n = 29)
      of obese non-diabetic women (r = -0.06, p = 0.77). The relationship between DHEAS
      and glycaemia homeostasis was also confirmed by significant negative correlation
      between DHEAS and glycated haemoglobin (HbA1c) both in the subgroup of type 2
      diabetic women (r = -0.51, p = 0.03) and in the subgroup of non-diabetic women (r
      = -0.70, p = 0.001). There was not found any significant correlation between
      DHEAS and insulin resistance neither in the whole group (n = 20) of obese men (r
      = 0.04, p = 0.87) nor in the subgroup (n = 11) of obese type 2 diabetic men (r =
      0.55, p = 0.08) or in the subgroup (n = 9) of obese non-diabetic men (r = -0.42,
      p = 0.26). CONCLUSIONS: Significant negative correlation between DHEAS and HOMA
      IR was found in the group of obese type 2 diabetic women but not in obese non
      diabetic women suggesting that low DHEAS level might be connected to the
      development of insulin resistance and type 2 diabetes mellitus in obese women.

PMID- 15717808
TI  - [Angiogenesis and antiangiogenic cancer therapy].
AB  - Physiologic angiogenesis takes place during tissue growth and repair, during the
      female reproductive cycle, and during fetal development. Angiogenesis is also
      required for tumor growth and metastasis and, therefore, represents an exciting
      target for cancer treatment. Angiogenesis is a complex process that is tightly
      regulated by pro- and antiangiogenic growth factors. Pathologic angiogenesis is
      characterized by either excessive (eg. cancer) or inadequate (eg. coronary artery
      disease) neovascularization. Avascular tumors are severely restricted in their
      growth potential because of the lack of a blood supply. For tumors to develop in
      size and metastatic potential they must make an "angiogenic switch" through
      perturbing the local balance of proangiogenic and antiangiogenic factors.
      Frequently, tumors overexpress proangiogenic factors, such as vascular
      endothelial growth factor, allowing them to make this angiogenic switch. Two
      strategies used in the development of antiangiogenic agents involve the
      inhibition of proangiogenic factors (eg. anti-vascular endothelial growth factor
      monoclonal antibodies) as well as therapy with endogenous inhibitors of
      angiogenesis. Emerging antiangiogenic agents currently in clinical studies are
      discussed in this review.

PMID- 15717809
TI  - [Huge sinus of Valsalva aneurysm in patient with cystic medial necrosis of the
      aorta].
AB  - In this case we present a patient with unruptured non-coronary sinus of Valsalva
      aneurysm associated with diverse clinical findings, caused by acquired
      degenerative changes of the aortic wall. A previously healthy 36-year-old female
      was admitted to the neurological clinic of our hospital having suffered from an
      episode of unconsciousness prior to admission, with accompanying seizures. For
      the preceding two months she had also been suffering from dyspnoea and
      palpitation. Neurological examination, computed tomography of the head and
      electroencephalography were with normal findings. Thereafter, due to paroxysm of
      supraventricular tachycardia she was referred to cardiology clinic. On routine
      physical examination a diastolic murmur was detected and the patient was referred
      for transthoracic echocardiography. This examination revealed a large, unruptured
      noncoronary sinus of Valsalva aneurysm, which was thereafter confirmed by
      transoesophageal echocardiography a angiography. The patient was indicated for
      surgical correction with aortic valve and aortic root replacement by Bentall
      procedure. Histological examination of the part of resected aneurysm found cystic
      medial degeneration of the aortic wall, also called cystic medial necrosis.

PMID- 15717810
TI  - Longitudinal analysis of efficiency in multiple output dialysis markets.
AB  - Provider efficiency in the dialysis industry in the U.S.A. has been of great
      interest for a variety of parties mainly because of the continuing growth in the
      number of such patients and providers and in the industry's costs. This study
      examined technical efficiency longitudinally among the multiple-output producers
      of freestanding facilities, as the dominant group of providers, using the DEA
      based Malmquist index. Nationally representative data were obtained from
      Independent Renal Facility Cost Report Data Files for the years 1994 through
      2000. The resulting sample comprised 140 facilities that had operated throughout
      the seven study years and jointly produced all dialysis outputs with nonzero
      inputs. The results show that over the period 1994-2000, on average multi-output,
      freestanding dialysis facilities did not achieve improvement in productivity.
      Decomposition of the Malmquist productivity indices showed improvement in
      technical efficiency but at the same time regress in technologies with potential
      to improve their quality of care. Negative change in technology was the major
      source of negative movement in productivity. The study concludes that under the
      fixed-price payment policy, multiple dialysis outputs are produced efficiently,
      but it may be that the quality of care is being sacrificed.

PMID- 15717811
TI  - Market capture of inpatient perioperative services using DEA.
AB  - We develop and validate a method to measure "market capture" of inpatient,
      elective surgery. Data envelopment analysis (DEA) is used to measure the
      efficiency of the market capture for Perioperative Services at 53 non
      metropolitan Pennsylvania hospitals. Eight procedures are studied, representing a
      wide spectrum of elective, scheduled, inpatient surgery (e.g., abdominal aortic
      aneurysm resection and hip replacement). Our results address issues in operating
      room management, such as: How should additional resources be allocated to each
      surgical specialty? Given existing market conditions, for which specialties can
      we expect to be able to increase our current workloads? Our results demonstrate
      DEA's potential as a valuable tool for operating room managers' strategic
      decision-making.

PMID- 15717812
TI  - The role of patients in designing health information systems: the case of
      applying simulation techniques to design an electronic patient record (EPR)
      interface.
AB  - One overall objective of Electronic Patient Records (EPRs) is to improve patient
      education and to enhance the patient experience through the use of information
      technology (IT) so as to facilitate the sharing of information between providers
      and their patients. The research project reported on herein took place at
      University Health Network (UHN) in Toronto (Canada), which is a large academic
      health science center with multiple hospital sites in the city. As a first step
      in this process, we examined the literature to investigate the human factors
      issues related to healthcare as well as other settings. Subsequently, we
      interviewed a number of interested stakeholders from two groups: the physicians
      (both family and attending) and the patients themselves. Finally, using a
      simulation environment, we explored the content that UHN lung-transplant patients
      would be interested in having within their own EPRs. In this paper, we report on
      the research, the methodology and the findings pertaining to the both the content
      and the design of an electronic patient record.

PMID- 15717813
TI  - Using Coxian phase-type distributions to identify patient characteristics for
      duration of stay in hospital.
AB  - Coxian phase-type distributions are a special type of Markov model that describes
      duration until an event occurs in terms of a process consisting of a sequence of
      latent phases. This paper considers the use of Coxian phase-type distributions
      for modelling patient duration of stay for the elderly in hospital and
      investigates the potential for using the resulting distribution as a classifying
      variable to identify common characteristics between different groups of patients
      according to their (anticipated) length of stay in hospital. The identification
      of common characteristics for patient length of stay groups would offer hospital
      managers and clinicians possible insights into the overall management and bed
      allocation of the hospital wards.

PMID- 15717814
TI  - Breast cancer screening services: trade-offs in quality, capacity, outreach, and
      centralization.
AB  - This work combines and extends previous work on breast cancer screening models by
      explicitly incorporating, for the first time, aspects of the dynamics of health
      care states, program outreach, and the screening volume-quality relationship in a
      service system model to examine the effect of public health policy and service
      capacity decisions on public health outcomes. We consider the impact of
      increasing standards for minimum reading volume to improve quality, expanding
      outreach with or without decentralization of service facilities, and the
      potential of queueing due to stochastic effects and limited capacity. The results
      indicate a strong relation between screening quality and the cost of screening
      and treatment, and emphasize the importance of accounting for service dynamics
      when assessing the performance of health care interventions. For breast cancer
      screening, increasing outreach without improving quality and maintaining capacity
      results in less benefit than predicted by standard models.

PMID- 15717815
TI  - Development of a decision support model for scheduling clinical studies and
      assigning medical personnel.
AB  - Clinical studies for the development of new drugs in the pharmaceutical industry
      consist of a number of individual tasks which have to be carried out in a pre
      defined chronological order. Each task requires certain types of medical
      personnel. This paper investigates the scheduling of clinical studies to be
      performed during a short-term planning horizon, the allocation of workforce
      between the studies, and the assignment of individual employees to tasks. Instead
      of developing a complex monolithic decision model, a hierarchical modelling
      approach is suggested. In the first stage, a compact integer optimization model
      is solved in order to determine the start-off times of the studies and the
      required staffing while taking the limited availability of personnel into
      account. The objective is to minimize total staffing costs. The assignment of
      individual employees to tasks is then made in the second stage of the procedure
      using a binary optimization model.

PMID- 15717816
TI  - Markov chain modeling of initiation and demand: the case of the U.S. cocaine
      epidemic.
AB  - Everingham and Rydell's Markov chain model of cocaine demand is modified and
      updated in light of recent data. Key insights continue to hold, e.g., that the
      proportion of cocaine demand stemming from heavy vs. light users changed
      dramatically over the 1980s. New insights emerge, e.g., pertaining to the average
      duration of a career of heavy use (about 12 years) and the negative relationship
      between levels of heavy use and epidemic "infectivity" or the number of new
      initiates per current user per year. This illustrates how simple modeling can
      yield insights directly relevant to managing complex drug control policy
      questions.

PMID- 15717817
TI  - Simulating the allocation of organs for transplantation.
AB  - The demand for donated organs greatly exceeds supply and many candidates die
      awaiting transplantation. Policies for allocating deceased donor organs may
      address equity of access and medical efficacy, but typically must be implemented
      with incomplete information. Simulation-based analysis can inform the policy
      process by predicting the likely effects of alternative policies on a wide
      variety of outcomes of interest. This paper describes a family of simulations
      developed by the US Scientific Registry of Transplant Recipients and initial
      experience in the application of one member of this family, the Liver Simulated
      Allocation Model (LSAM).

PMID- 15717818
TI  - Formulation and implementation of a phase-resolved fluorescence technique for
      latent-fingerprint imaging: theoretical and experimental analysis.
AB  - A theoretical and experimental study of the imaging of latent fingerprints by a
      phase-resolved fluorescence technique along with associated signal-processing
      analysis is described. The system configuration is optimized by incorporation of
      a novel approach of homodyne-assisted even-step phase shifting in a signal
      processing concept. The excitation laser source and gain of the detection device,
      which are modulated at megahertz frequency followed by sensitive signal
      processing concepts, are employed to separate the fingerprint fluorescence from
      background fluorescence. Experiments are carried out with fingerprints deposited
      upon different types of substrate surfaces. Later, a quantitative image-quality
      assessment is carried out, which confirms the improvement in the quality of the
      phase-resolved fingerprint image. Imaging of older fingerprints with better
      contrast is also carried out with the proposed novel technique.

PMID- 15717819
TI  - Scalable high-resolution integral videography autostereoscopic display with a
      seamless multiprojection system.
AB  - We propose a scalable high-resolution autostereoscopic display that uses integral
      videography (IV) and a seamless multiprojection system. IV is an animated
      extension of integral photography (IP). Although IP and IV are ideal ways to
      display three-dimensional images, their spatial viewing resolution needs
      improvement; the pixel pitch of the display and the lens pitch are the main
      factors affecting IV image quality. We improved the quality by increasing the
      number and density of the pixels. Using multiple projectors, we create a scalable
      high-resolution image and project it onto a small screen using long-focal-length
      projection optics. To generate seamless IV images, we developed an image
      calibration method for geometric correction and color modulation. We also
      fabricated a lens array especially for the display device. Experiments were
      conducted with nine XGA projectors and nine PCs for parallel image rendering and
      displaying. A total of 2868 x 2150 pixels were displayed on a 241 mm x 181 mm
      (302.4 dots/in.) rear-projection screen. The lens pitch was 1.016 mm,
      corresponding to 12 pixels of the projected image. Measurement of the geometric
      accuracy of the reproduced IV images demonstrated that the spatial resolution of
      the display system matched that of the theoretical analysis.

PMID- 15717820
TI  - Microinterferometric optical phase tomography for measuring small, asymmetric
      refractive-index differences in the profiles of optical fibers and fiber devices.
AB  - A new technique, microinterferometric optical phase tomography, is introduced for
      use in measuring small, asymmetric refractive-index differences in the profiles
      of optical fibers and fiber devices. The method combines microscopy-based fringe
      field interferometry with parallel projection-based computed tomography to
      characterize fiber index profiles. The theory relating interference measurements
      to the projection set required for tomographic reconstruction is given, and
      discrete numerical simulations are presented for three test index profiles that
      establish the technique's ability to characterize fiber with small, asymmetric
      index differences. An experimental measurement configuration and specific
      interferometry and tomography practices employed in the technique are discussed.

PMID- 15717821
TI  - Michelson wide-field stellar interferometry: principles and experimental
      verification.
AB  - A new interferometric technique for Michelson wide-field interferometry is
      presented that consists of a Michelson pupil-plane combination scheme in which a
      wide field of view can be achieved in one shot. This technique uses a stair
      shaped mirror in the intermediate image plane of each telescope in the array,
      allowing for simultaneous correction of the differential delay for the on-axis
      and off-axis image positions. Experimental results in a laboratory setup show
      that it is possible to recover the fringes of on-axis and off-axis stars with an
      angular separation of 1 arc min simultaneously and with a similar contrast. This
      new technique represents a considerable extension of the field of view of an
      interferometer without the need for extra observation time.

PMID- 15717822
TI  - Some opportunities for vibration analysis with time averaging in digital Fresnel
      holography.
AB  - Features offered by the combination of time averaging and digital Fresnel
      holography are investigated. In particular, we introduce the concept of the zero
      crossing phase of Bessel fringes, which allows a highly contrasted determination
      of the dark fringes in the hologram. We discuss some particularities of the
      digital reconstruction and show how time-averaged digital holography can be used
      to study vibration drifts. Experiment results are presented in the case of a
      loudspeaker under a sinusoidal excitation; digital and analogical holography are
      also compared.

PMID- 15717823
TI  - Use of Michelson and Fabry-Perot interferometry for independent determination of
      the refractive index and physical thickness of wafers.
AB  - We present a method to independently measure the refractive index and the
      thickness of materials having flat and parallel sides by using a combination of
      Michelson and Fabry-Perot interferometry techniques. The method has been used to
      determine refractive-index values in the infrared with uncertainties in the third
      decimal place and thicknesses accurate to within +/- 5 microm for materials at
      room and cryogenic temperatures.

PMID- 15717824
TI  - Direct bidirectional angle-insensitive imaging of the flow signal intensity in
      Doppler optical coherence tomography.
AB  - We introduce a new method, to our knowledge, for direct detection of flow signal
      intensity by stationary target rejection. In our system, two delay lines are
      constructed with identical scanning speed and ranging depth. One delay line is
      used for depth ranging as well as phase modulation, and the other one acts as a
      full-range retroreflector (FRRR). The signal from this FRRR carries the overall
      features of local phase modulation, and it is used as the local oscillator for
      coherent demodulation. With this setup, stationary targets can be rejected at a 4
      kHz high-pass cutoff frequency of the filter that follows the demodulator,
      compared with 20 kHz for conventional fixed-frequency demodulation. This
      technique features angle insensitivity and provides flow direction as well by
      implementing standard in-phase and quadrature detection. Besides the direct
      directional detection of flow signal intensity, flow speed information can be
      acquired with postprocessing.

PMID- 15717825
TI  - Characterization of depolarizing optical media by means of the entropy factor:
      application to biological tissues.
AB  - Polarized light imaging is a potential tool to obtain an adequate description of
      the properties of depolarizing media such as biological tissues. In many
      biomedical applications, for instance, dermatology, ophthalmology, or urology,
      imaging polarimetry provides a noninvasive diagnosis of a wide range of disease
      states, and, likewise, it could be applied to the study of internal tissues
      though the use of endoscopes that use optical fibers. We introduce an algebraic
      method, based on the Mueller-coherence matrix, for a clearer analysis of the
      polarization characteristics of depolarizing media via the entropy factor. First
      order errors introduced by the measurement system are corrected. Entropy defines
      three kinds of media according to their depolarizing behavior, and several
      examples corresponding to each region are shown. The calculation of this factor
      provides clearer information than that provided by the traditional Mueller matrix
      in the analysis of biological tissue properties by polarization measurement
      techniques.

PMID- 15717826
TI  - Low-coherent backscattering spectroscopy for tissue characterization.
AB  - Although the phenomenon of coherent backscattering (CBS) in nonbiological media
      has generated substantial research interest, observing CBS in biological tissue
      has been extremely difficult. Here we show that the combination of low-spatial
      coherence, broadband illumination, and low-temporal-coherence, spectrally
      resolved detection significantly facilitates CBS observation in biological tissue
      and other random media with long-transport mean-free path lengths, which have
      been previously beyond the reach of conventional CBS investigations. Furthermore,
      we demonstrate that depth-selective, speckle-free, low-coherent backscattering
      spectroscopy has the potential to diagnose the earliest, previously undetectable,
      precancerous alterations in the colon by means of probing short light paths.

PMID- 15717827
TI  - Titania, silicon dioxide, and tantalum pentoxide waveguides and optical resonant
      filters prepared with radio-frequency magnetron sputtering and annealing.
AB  - Mixing dielectric materials in solid-thin-film deposition allows the engineering
      of thin films' optical constants to meet specific thin-film-device requirements,
      which can be significantly useful for optoelectronics devices and photonics
      technologies in general. In principle, by use of radio-frequency (rf) magnetron
      sputtering, it would be possible to mix any two, or more, materials at different
      molar ratios as long as the mixed materials are not chemically reactive in the
      mixture. This freedom in material mixing by use of magnetron sputtering has an
      advantage by providing a wide range of the material optical constants, which
      eventually enables the photonic-device designer to have the flexibility to
      achieve optimal device performance. We deposited three combinations from three
      different oxides by using rf magnetron sputtering and later investigated them for
      their optical constants. Each two-oxide mixture was done at different molar ratio
      levels. Moreover, postdeposition annealing was investigated and was shown to
      reduce the optical losses and to stabilize the film composition against
      environmental effects such as aging and humidity exposure. These investigations
      were supported by the fabricated planar waveguides and optical resonant filters.

PMID- 15717828
TI  - Study of normal incidence of three-component multilayer mirrors in the range 20
      40 nm.
AB  - We study theoretically and experimentally the increase of normal incidence
      reflectivity generated by addition of a third material in the period of a
      standard periodic multilayer, for wavelengths in the range 20 to 40 nm. The
      nature and thickness of the three materials has been optimized to provide the
      best enhancement of reflectivity. Theoretical reflectivity of an optimized
      B4C/Mo/Si multilayer reaches 42% at 32 nm. B4C/Mo/Si multilayers have been
      deposited with a magnetron sputtering system and a reflectivity of 34% at 32 nm
      has been measured on a synchrotron radiation source.

PMID- 15717829
TI  - Long-range detection and length estimation of light filaments using extra
      attenuation of terawatt femtosecond laser pulses propagating in air.
AB  - High-energy femtosecond laser pulses propagating in the atmosphere undergo self
      focusing resulting in the appearance of the phenomenon of filamentation. We
      observed an extra-attenuation of such (terawatt) femtosecond laser pulses
      propagating in the atmosphere when compared with long pulses (200 ps) with the
      same energy. This is because, in contrast to the linear propagation of the long
      pulse, the input femtosecond laser pulse is attenuated owing to either absorption
      through multiphoton ionization/tunnel ionization or to scattering on the laser
      induced plasma; self-phase-modulation and self-steepening further convert
      partially the energy initially contained in the fundamental bandwidth into the
      broad side bands of the laser, becoming eventually a white-light laser pulse
      (supercontinuum). The experimental data allow us to extract an effective extra
      attenuation coefficient for an exponential decay of the input pulse energy with
      the propagation distance. Such a coefficient allows us to estimate an upper bound
      of the filament length under the experimental conditions used. More generally,
      our observation leads to a new technique to remotely detect light filaments in
      the atmosphere.

PMID- 15717830
TI  - Measurements of the infrared emissivity of a wind-roughened sea surface.
AB  - Spectral statistical-analysis techniques were developed and applied to high
      spectral-resolution infrared measurements of the sea surface. The effective
      incidence angle of a ship-borne instrument in typical at-sea conditions was found
      to introduce errors of up to 0.7 K in sea-surface temperature retrievals at a 55
      degrees view angle. The sea-surface emissivity was determined over the 8-12
      microm window at view angles of 40 degrees and 55 degrees and at wind speeds up
      to 13 ms(-1). The emissivity was found to increase in magnitude with increasing
      wind speed, rather than decrease, as predicted by widely used parameterizations.
      Use of these parameterizations can cause significant bias in remote sensing of
      sea-surface temperature in noncalm conditions.

PMID- 15717831
TI  - Effect of bio-optical parameter variability on the remote estimation of
      chlorophyll-a concentration in turbid productive waters: experimental results.
AB  - The analytical development and underlying hypothesis of a three-band algorithm
      for estimating chlorophyll-a concentration ([Chla]) in turbid productive waters
      are presented. The sensitivity of the algorithm to the spectral location of the
      bands used is analyzed. A large set of experimental observations ([Chla] varied
      between 4 and 217 mg m(-3) and turbidity between 2 and 78 nephelometric turbidity
      units) was used to calibrate and validate the algorithm. It was found that the
      variability of the chlorophyll-a fluorescence quantum yield and of the
      chlorophyll-a specific absorption coefficient can reduce considerably the
      accuracy of remote predictions of [Chla]. Instead of parameterizing these
      interferences, their effects were minimized by tuning the spectral regions used
      in the algorithm. This allowed us to predict [Chla] with a relative root-mean
      square error of less than 30%.

PMID- 15717832
TI  - Optical detection of rapidly moving objects in space.
AB  - We compare the sensitivity of photon-counting and charged-coupled-device (CCD)
      imagers for rapidly moving objects. Our test case involves the detection of small
      objects in space, seen against a diffuse zodiacal light background, as observed
      from a space platform. We contrast photon-counting detectors, with excellent time
      resolution and negligible readout noise, against CCDs with a significantly larger
      quantum efficiency. For fast moving objects and small fields of view, the photon
      counting detectors are able to detect significantly smaller targets, with the
      added benefit of providing angle-angle-time metric information in addition to
      high-time-resolution light curves. For larger fields of view and slower moving
      objects, the CCDs are more sensitive. These results may motivate the further
      development of microchannel-plate photon-counting systems and amplified CCDs for
      detecting and tracking space objects.

PMID- 15717833
TI  - Airborne system for fast measurements of upwelling and downwelling spectral
      actinic flux densities.
AB  - An airborne system for fast measurements of spectral actinic flux densities in
      the wavelength range 305-700 nm is introduced. The system is called the Actinic
      Flux Density Meter (AFDM). The AFDM utilizes the diode array technique and
      measures downwelling and upwelling spectral actinic flux densities separately
      with a time resolution of less than 1 s. For airborne measurements this means a
      spatial resolution of approximately 60 m, assuming an average aircraft velocity
      of 60 m/s. Thus the AFDM resolves fast changes in the actinic radiation field,
      which are of special importance for conditions of inhomogeneous clouds or surface
      reflection. Laboratory characterization measurements of the AFDM are presented,
      and a method to correct the nonideal angular response of the optical inlets is
      introduced. Furthermore, exemplar field data sampled simultaneously with spectral
      irradiance measurements are shown. The horizontal variability of the measured
      spectra of actinic flux density is quantified, and profile measurements for
      overcast situations are presented. Finally, the effects of clouds on the spectral
      actinic flux density are discussed.

PMID- 15717834
TI  - Simultaneous planar laser-induced incandescence, OH planar laser-induced
      fluorescence, and droplet Mie scattering in swirl-stabilized spray flames.
AB  - Simultaneous planar laser-induced incandescence, hydroxyl radical planar laser
      induced fluorescence, and droplet Mie scattering are used to study the
      instantaneous flame structure and soot formation process in an atmospheric
      pressure, swirl-stabilized, liquid-fueled, model gas-turbine combustor. Optimal
      excitation and detection schemes to maximize single-shot signals and avoid
      interferences from soot-laden flame emission are discussed. The data indicate
      that rich pockets of premixed fuel and air along the interface between the spray
      flame and the recirculation zone serve as primary sites for soot inception.
      Intermittent large-scale structures and local equivalence ratio are also found to
      play an important role in soot formation.

PMID- 15717835
TI  - Retrieval of trace gases from aerosol-influenced infrared transmission spectra
      observed by low-spectral-resolution Fourier-transform spectrometers.
AB  - A method for the simultaneous retrieval of gas concentrations and an extinction
      spectrum of aerosols and polar stratospheric clouds from infrared transmission
      spectra observed in the solar occultation geometry is described. It is
      particularly suited to measurements by Fourier-transform spectrometers with
      relatively low spectral resolution (0.1-1 cm(-1)). The method does not require a
      priori assumptions on aerosol properties; it utilizes only the fact that the wave
      number dependence of aerosol extinction is much weaker than that of gas
      absorption. In this method, an aerosol extinction spectrum is approximated by a
      straight line within a relatively wide spectral range defined as mediumwindow.

PMID- 15717836
TI  - Emerging role of Akt kinase/protein kinase B signaling in pathophysiology of
      diabetes and its complications.
AB  - In addition to a number of deleterious effects on cellular integrity and
      functions, diabetic metabolic milieu has been implicated in a rapidly growing
      number of alterations in signal transduction. In this review we focus on Akt
      kinase physiology, its alterations in diabetes mellitus (DM), and on the emerging
      role of this signaling system in the pathophysiology of diabetic microvascular
      complications. Studies focusing on Akt in diabetes suggest both decrease and
      increase of Akt activity in DM. Alterations of Akt activity have been found in
      various tissues and cells in diabetes depending on experimental and clinical
      contexts. There is convincing evidence suggesting defective Akt signaling in the
      development of insulin resistance. Similar defects, as in insulin-sensitive
      tissues, have been reported in endothelia of DM Type 2 models, possibly
      contributing to the development of endothelial dysfunction under these
      conditions. In contrast, Akt activity is increased in some tissues and vascular
      beds affected by complications in DM Type 1. Identification of the role of this
      phenomenon in DM-induced growth and hemodynamic alterations in affected vascular
      beds remains one of the major challenges for future research in this area. Future
      studies should include the evaluation of therapeutical benefits of
      pharmacological modulators of Akt activity.

PMID- 15717837
TI  - Effects of sodium restriction and cyclooxygenase-2 inhibition on the course of
      hypertension, proteinuria and cardiac hypertrophy in Ren-2 transgenic rats.
AB  - The present study was performed to evaluate the effects of sodium intake and of
      chronic cyclooxygenase-2 (COX-2) inhibition on systolic blood pressure (SBP) in
      heterozygous male transgenic rats harboring the mouse Ren-2 renin gene (TGR) and
      in transgene-negative normotensive Hannover Sprague-Dawley (HanSD). Twenty-eight
      days old TGR and HanSD were randomly assigned to groups fed either normal salt
      (NS) or low sodium (LS) diets. COX-2 blockade was achieved with NS-398 (1 mg x
      kg(-1).day(-1) in drinking water). During an experimental period of 26 days, SBP
      was repeatedly measured by tail plethysmography in conscious animals. We found
      that the LS diet prevented the development of hypertension in TGR and did not
      change SBP in HanSD. Low sodium intake also prevented proteinuria and cardiac
      hypertrophy in TGR. On the other hand, irrespective of sodium intake chronic COX
      2 inhibition did not alter the course of SBP in either TGR or HanSD. The present
      data indicate that TGR exhibit an important salt-sensitive component in the
      developmental phase of hypertension. They also suggest that systemic COX-2
      derived prostaglandins do not act as vasodilatory counterregulatory agents in TGR
      in which an exaggerated vascular responsiveness to angiotensin II is assumed as
      the pathophysiological mechanism in the development of hypertension.

PMID- 15717838
TI  - Ischemia reperfusion injury of the skeletal muscle after selective
      deafferentation.
AB  - The present study analyzes the effect of selective deafferentation on the
      reperfusion injury of the skeletal muscle when nociceptive sensory fibers of the
      left sciatic nerve are selectively damaged by capsaicin pretreatment in a rat
      model following tourniquet ischemia (ISC) applied for 30 min, 1 h, and 2 h on the
      left hind limb. The isometric tetanic contractile force of the extensor digitorum
      longus (EDL) muscle was measured after 1 h, and 1, 3, or 7 days of reperfusion.
      Contractile force of the damaged muscle was compared to the intact contralateral
      muscle. In another group, ISC was used without capsaicin pre-treatment. After 30
      min of ISC, there was no difference between deafferented and non-pretreated
      groups. Following 1 h ISC, with the exception of 1 h reperfusion, the non
      pretreated group produced stronger contractions than the deafferented group.
      After 2 h ISC, the contractile force of the deafferented muscle was significantly
      stronger compared to the non-deafferented muscle force at all reperfusion times.
      In conclusions, it was found that the absence of peptidergic sensory fibers after
      long-lasting (2 h) ischemia is beneficial in reperfusion injury, whereas the
      absence of vasodilator peptides has unfavorable effects if tissue damage is
      milder (after 1 h ischemia).

PMID- 15717839
TI  - Short-term very low calorie diet reduces oxidative stress in obese type 2
      diabetic patients.
AB  - Oxidative stress is higher in obese diabetic than in non-diabetic subjects. This
      pilot study evaluates oxidative stress during short-term administration of a very
      low calorie diet in obese persons. Nine obese Type 2 diabetic patients (age 55+/
      5 years, BMI 35.9+/-1.9 kg/m2) and nine obese non-diabetic control subjects (age
      52+/-6 years, BMI 37.3+/-2.1 kg/m2) were treated by a very low calorie diet (600
      kcal daily) during 8 days stay in the hospital. Serum cholesterol, triglycerides,
      non-esterified fatty acids (NEFA), beta-hydroxybutyrate (B-HB), ascorbic acid
      (AA), alpha-tocopherol (AT), plasma malondialdehyde (MDA) and superoxide
      dismutase (SOD) activity in erythrocytes were measured before and on day 3 and 8
      of very low calorie diet administration. A decrease of serum cholesterol and
      triglyceride concentrations on day 8 was associated with a significant increase
      of NEFA (0.30+/-0.13 vs. 0.47+/-0.11 micromol/l, p<0.001) and B-HB (0.36+/-.13
      vs. 2.23+/-1.00 mmol/l, p<0.001) in controls but only of B-HB (1.11+/-0.72 vs.
      3.02+/-1.95 mmol/l, p<0.001) in diabetic patients. A significant decrease of
      plasma MDA and serum AT together with an increase of SOD activity and AA
      concentration (p<0.01) was observed in control persons, whereas an increase of
      SOD activity (p<0.01) was only found in diabetic patients after one week of the
      very low calorie diet. There was a significant correlation between NEFA or B-HB
      and SOD activity (p<0.01). We conclude that one week of a very low calorie diet
      administration decreases oxidative stress in obese non-diabetic but only partly
      in diabetic persons. Diabetes mellitus causes a greater resistance to the effects
      of a low calorie diet on oxidative stress.

PMID- 15717840
TI  - Screening for associated autoimmunity in type 1 diabetes mellitus with respect to
      diabetes control.
AB  - As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with
      other autoimmune disorders. The aim of this study was to detect subclinically
      associated autoimmune thyroid disease, coeliac disease, and Addison's disease.
      The presence of autoantibodies was evaluated with special regard to the control
      of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic
      patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes
      16+/-13 years) were included into this study. Specific antibodies to islet
      antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA
      2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and
      thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by
      RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies
      (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by
      ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were
      detected by indirect immunofluorescence microscopy. Eleven new cases of
      thyreopathy (22 % of patients) were detected by the assessment of thyroid
      autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during
      the study. Coeliac disease was diagnosed in at least two cases. Addison's disease
      was not diagnosed, although the ACA were positive in two patients. No influence
      of single or combined autoantibody positivity on the control of diabetes was
      found if normal organ function was preserved. In both patients with
      thyreotoxicosis the control of diabetes was worsened and improved after
      treatment. The screening of autoantibodies in type 1 diabetic patients could
      reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these
      disorders have no influence on diabetes control. However, impaired organ function
      may be associated with the worsened control of diabetes as we demonstrated on two
      newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up
      of patients with positive autoantibodies because further deterioration of the
      respective organs can be expected.

PMID- 15717842
TI  - Lipid metabolism of monosodium glutamate obese rats after partial removal of
      adipose tissue.
AB  - We analyzed the effects of partial fat pad removal on retroperitoneal and
      epididymal fat depots and carcass metabolism of control (C) and MSG-obese (M)
      rats. Three-month-old C and M male Wistar rats were submitted to either partial
      surgical excision of epididymal and retroperitoneal fat tissue (lipectomy, L) or
      sham surgery (S) and studied after 7 or 30 days. Retroperitoneal and epididymal
      tissue re-growth after lipectomy was not observed, as indicated by the low pads
      weight of the L groups. The lipolysis rate was stimulated in LC7 and LM7,
      probably due to surgical stress and low insulin levels. In LM7, but not in LC7,
      in vivo lipogenesis rate increased in retroperitoneal and epididymal fat tissue,
      as did the diet-derived lipid accumulation in epididymal fat tissue. Although
      these local increases were no longer present in LM30, this group showed a large
      increase in the percentage of small area adipocytes in both pads as well as
      increased carcass lipogenesis rate. The present data showed that the partial
      removal of fat depots affected the metabolism of control and MSG-obese rats
      differently. In the obese animals only, it stimulated both local and carcass
      lipogenesis rate as well as adipocyte differentiation, i.e. responses likely to
      favor excised tissue re-growth and/or compensatory growth of non-excised depots.

PMID- 15717841
TI  - Temporal relationship between lens protein oxidation and cataract development in
      streptozotocin-induced diabetic rats.
AB  - We compared the progression of lens opacification with the time course of
      oxidation of lens proteins under conditions of streptozotocin-induced
      experimental diabetes in rats. By the end of the 17th week, approx. 50% of the
      diabetic animals developed mature cataracts. During the following month, 95% of
      the eyes in the diabetic group became cataractous. In the course of lens
      opacification we observed a time-dependent increase in the content of protein
      carbonyls and decrease in the concentration of protein sulfhydryls in the lenses
      of diabetic animals. Significantly higher protein carbonyl (p<0.01) and lower
      protein sulfhydryl (p<0.001) content was found in lenses with the advanced stage
      of cataract when compared with the diabetic lenses still transparent. We showed
      that the values of protein carbonyls exceeding 1.2 nmol/mg protein and of
      sulfhydryls falling below 60 nmol/mg protein corresponded to an approximately 50%
      incidence of mature cataract development. At the end of the 34th week, when all
      lenses of diabetic rats became cataractous, the corresponding values of protein
      carbonyls and sulfhydryls were 2.5 nmol/mg protein and 27 nmol/mg protein,
      respectively. The main finding of this study is the disclosure of quantitative
      relationship between the degree of protein oxidation and the rate of advanced
      cataract development in the widely used model of streptozotocin-induced
      experimental diabetes in rats.

PMID- 15717843
TI  - Tert-butyl hydroperoxide selectively inhibits mitochondrial respiratory-chain
      enzymes in isolated rat hepatocytes.
AB  - Sensitivity of various mitochondrial enzymes to oxidative damage was tested on
      isolated rat liver hepatocytes permeabilized by digitonin. In permeabilized
      hepatocytes normal respiratory control values were obtained and mitochondrial
      membranes remained intact. Respiratory rates of NADH-dependent (glutamate +
      malate, palmitylcarnitine + malate) and flavoprotein-dependent (succinate)
      substrates were determined in hepatocytes exposed for 5 min to 0.5-3 mM tert
      butyl hydroperoxide before addition of digitonin. Our data showed that oxidation
      of NADH-dependent substrates is much more sensitive to oxidative stress than
      oxidation of flavoprotein-dependent ones, evidently due to the modification of
      iron-sulfur clusters or SH groups in the NADH dehydrogenase enzyme complex
      (Complex I).

PMID- 15717844
TI  - Adipocyte-derived hormones in heroin addicts: the influence of methadone
      maintenance treatment.
AB  - Heroin addiction markedly affects the nutritional and metabolic status and
      frequently leads to malnutrition. The aim of our study was to compare circulating
      concentration of adipose tissue-derived hormones leptin, adiponectin and resistin
      in 12 patients with heroin addiction before and after one-year methadone
      maintenance treatment with the group of 20 age- and body mass index-matched
      healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts
      were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs.
      33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations
      were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p
      0.05). Moreover, positive correlation of serum leptin levels with body mass index
      was lost in the addicts in contrast to control group. One year of methadone
      maintenance treatment normalized serum leptin, but not serum adiponectin and
      resistin concentrations. In conclusion, circulating concentrations of leptin,
      adiponectin and resistin are markedly altered in patients with chronic heroin
      addiction. These alterations appear to be relatively independent of nutritional
      status and insulin sensitivity.

PMID- 15717845
TI  - Leptin secretion and protein kinase A activity.
AB  - Leptin is an adipocyte-derived hormone participating in the regulation of food
      intake and energy balance. Its secretion from fat cells is potentiated by insulin
      and by substrates providing ATP, whereas factors increasing cAMP level attenuate
      hormone release stimulated by insulin and glucose. The present experiments were
      aimed to determine the effect of cAMP on leptin secretion stimulated by glucose,
      alanine or leucine in the presence of insulin. Moreover, the effect of protein
      kinase A inhibition on leptin secretion was tested. To stimulate leptin
      secretion, isolated rat adipocytes were incubated for 2 h in the buffer
      containing 5 mmol/l glucose, 10 mmol/l alanine or 10 mmol/l leucine, all in the
      presence of 10 nmol/l insulin. Inhibition of protein kinase A (PKA) by H-89 (50
      micromol/l) slightly enhanced leptin release stimulated by glucose and leucine
      but not by alanine. Activation of this enzyme by dibutyryl-cAMP (1 mmol/l)
      substantially restricted leptin secretion stimulated by glucose, alanine and
      leucine. The inhibitory influence of dibutyryl-cAMP on leptin secretion was
      totally (in the case of stimulation induced by glucose) or partially (in the case
      of stimulation by alanine and leucine) suppressed by H-89. These results
      demonstrate that leptin secretion induced by glucose, alanine and leucine is
      profoundly attenuated by cAMP in PKA-dependent manner. Therefore, the action of
      different stimulators of leptin secretion may be restricted by agents increasing
      the cAMP content in adipocytes. Moreover, it has also been shown that inhibition
      of PKA evokes the opposite effect and enhances leptin release.

PMID- 15717846
TI  - The influence of folate and antioxidants on homocysteine levels and oxidative
      stress in patients with hyperlipidemia and hyperhomocysteinemia.
AB  - The aim of this study was to observe the effect of folate and antioxidants alone
      on homocysteine levels and oxidative stress markers, and to evaluate whether
      their co-administration promotes their effects. One hundred patients with
      hyperhomocysteinemia were randomized into four equal groups, which were then
      treated with folate, antioxidants or folate plus antioxidants for 2 months; group
      IV was a control group. Serum homocysteine, folate and oxidative stress markers
      were measured before the study, at the end of folate and/or antioxidants
      administration and 3 months later. Folate caused a significant decrease in
      homocysteine concentration. Antioxidants did not influence homocysteine
      concentration, but they improved the antioxidative defense (plasma antioxidant
      capacity and intraerythrocyte glutathione were increased) and partially prevented
      lipid peroxidation (malondialdehyde level was slightly decreased).
      Supplementation with folate had a similar effect on intracellular glutathione and
      plasma malondialdehyde. Simultaneous administration of folate and antioxidants
      did not show any additive effect with the exception of a slower decrease of
      folate concentration after its supplementation had been discontinued. Folate may
      be considered as an effective antioxidant in patients with hyperhomocysteinemia;
      this can be a result of decreased production of free radicals due to a reduced
      level of homocysteine. Its antioxidative effect cannot be promoted by co
      administration of antioxidants.

PMID- 15717847
TI  - Met-enkephalin modulation of age-related changes in red cell antioxidant status.
AB  - Opioid peptides have been recognized as modulators of reactive oxygen species
      (ROS) in mouse macrophages and human neutrophils. Since the effect cannot be
      ascribed to its direct scavenger properties, in this study, we tested the
      hypothesis that methionine-enkephalin (MENK) modulates ROS by alteration of
      antioxidant enzyme activity (AOE). For this purpose superoxide dismutase (SOD),
      catalase (CAT) and glutathione peroxidase (GPX) are measured in red blood cells
      of 1, 4, 10, and 18-month-old CBA mice of both sexes injected with 10 mg/kg MENK.
      The results indicate that MENK-affected antioxidant enzyme activity of red blood
      cells is age- but not sex-related. The most abundant effects were observed at the
      reproductive stage. Increased sensitivity to oxidative stress by opioid peptides
      was in both sexes mainly due to increased SOD activity followed by GPX decrease.
      Thus, the damage ascribed to opioid peptides might be, at least partly, ascribed
      to deleterious effects of accumulated hydrogen peroxide (H2O2).

PMID- 15717848
TI  - Oxidative activity of human polymorphonuclear leukocytes stimulated by the long
      chain phosphatidic acids.
AB  - It has already been suggested that phosphatidic acids (PAs) play an important
      role in the regulation of signaling pathways involved in the production of
      reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs). The
      present study was performed to elucidate the effects of extracellularly added PA-
      1,2-distearoyl- (DSPA) and 1-stearoyl-2-arachidonoyl-sn-glycero-phosphate (SAPA)
      -on the ROS production and on the elastase release by human PMNs. ROS production
      was monitored by luminol-amplified chemiluminescence and the elastase activity
      was measured in the supernatant of the PA-stimulated human PMNs by colorimetric
      assay. Obtained effects were compared with those of cells stimulated by either a
      chemotactic tripeptide, phorbol ester or calcium ionophore. Our results show that
      long-chain PAs at concentrations higher than 3 x 10(-5) mol/l stimulate the ROS
      production by human PMNs, whereas they were ineffective in promoting the elastase
      release. The chemiluminescence pattern of the SAPA-stimulated cells exhibited a
      biphasic curve, whereas cell stimulation with DSPA resulted in a monophasic
      chemiluminescence curve. Stimulation of the ROS production by PAs in dependence
      of the fatty acid composition required the activity of protein kinases.

PMID- 15717849
TI  - Neural differentiation of pluripotent mouse embryonal carcinoma cells by retinoic
      acid: inhibitory effect of serum.
AB  - In both embryonal carcinoma (EC) and embryonic stem (ES) cells, the
      differentiation pathway entered after treatment with retinoic acid (RA) varies as
      it is based upon different conditions of culture. This study employs mouse EC
      cells P19 to investigate the effects of serum on RA-induced neural
      differentiation occurring in a simplified monolayer culture. Cell morphology and
      expression of lineage-specific molecular markers document that, while non-neural
      cell types arise after treatment with RA under serum-containing conditions, in
      chemically defined serum-free media RA induces massive neural differentiation in
      concentrations of 10(-9) M and higher. Moreover, not only neural (Mash-1) and
      neuroectodermal (Pax-6), but also endodermal (GATA-4, alpha-fetoprotein) genes
      are expressed at early stages of differentiation driven by RA under serum-free
      conditions. Furthermore, as determined by the luciferase reporter assay, the
      presence or absence of the serum does not affect the activity of the retinoic
      acid response element (RARE). Thus, mouse EC cells are able to produce neural
      cells upon exposure to RA even without culture in three-dimensional embryoid
      bodies (EBs). However, in contrast to standard EBs-involving protocol(s), neural
      differentiation in monolayer only takes place when complex signaling from serum
      factors is avoided. This simple and efficient strategy is proposed to serve as a
      basis for neurodifferentiation studies in vitro.

PMID- 15717850
TI  - The influence of low-frequency left prefrontal repetitive transcranial magnetic
      stimulation on memory for words but not for faces.
AB  - Brain imaging studies suggest localization of verbal working memory in the left
      dorsolateral prefrontal cortex (DLPFC) while face processing and memory is
      localized in the inferior temporal cortex and other brain areas. The goal of this
      study was to assess the effect of left DLPFC low-frequency repetitive
      transcranial magnetic stimulation (rTMS) on verbal recall and face recognition.
      The study revealed a significant decrease of free recall in word encoding under
      rTMS (110% of motor threshold, 0.9 Hz) in comparison with sham stimulation
      (p=0.03), while no significant difference was found with facial memory tests. Our
      findings support the essential role of the left DLPFC in word but not facial
      memory and confirm the content specific arrangement of cortical areas involved in
      semantic memory. As a non-invasive tool, rTMS is useful for cognitive brain
      mapping and the functional localization of the category specific memory system.

PMID- 15717851
TI  - Calcium dependence of uni-quantal release latencies and quantal content at mouse
      neuromuscular junction.
AB  - Uni-quantal endplate currents (EPC) were recorded at mouse diaphragm
      neuromuscular synapse by extracellular microelectrode during motor nerve
      stimulation. The probability of release expressed as quantal content m(o), and
      variability of synaptic latencies expressed as P90 were estimated in the presence
      of extracellular calcium ([Ca2+]o) varying between 0.2 and 0.6 mM in the bathing
      solution. At 0.2 mM ([Ca2+]o), m(o) was low (0.10) and many of long-latency EPCs
      were present during the late phase of the release (P90 = 2.44 ms). No change in
      m(o) was found when ([Ca2+]o) was 0.3 mM, but P90 decreased by 39 %. For latency
      shortening, saturating concentration of ([Ca2+]o) was 0.4 mM, when P90 was 1.49
      ms and latencies did not further change at 0.5 and 0.6 mM ([Ca2+]o). In the
      latter concentrations, however, an increase of m(o) was still observed. It can be
      concluded that the early phase of the secretion did not significantly change when
      ([Ca2+]o) was raised and that only the late phase of the release depends on
      extracellular calcium up to 0.4 mM.

PMID- 15717852
TI  - Cross-generational effect of prenatal morphine exposure on neurobehavioral
      development of rat pups.
AB  - Prenatal exposure to opiates can have devastating effects on the development of
      human fetuses and may induce long-term physical and neurobehavioral changes
      during postnatal maturation. The present study was aimed at identifying cross
      generational effects of prenatal morphine exposure in Sprague-Dawley rats.
      Pregnant rats were injected subcutaneously with either saline or morphine (10
      mg/kg) twice daily during gestational days 11-18. Litter size, percentage of
      males and females, anogenital distances (AGDs), righting reflex, and body weight
      were assessed in prenatally morphine-exposed pups (first generation) and their
      offspring (second generation). Both prenatally morphine-exposed pups and
      offspring of prenatally morphine-exposed dams exhibited an increased latency to
      right. Additionally, second generation pups were slower in righting than first
      generation pups. During the early postnatal period the second generation pups
      weighed less than the first generation regardless of drug exposure. The AGDs of
      second generation male pups were decreased relative to the first generation. Our
      data provide important novel information about the trans-generational effects of
      maternal opiate abuse that may be useful for understanding/evaluating the
      teratogenic effects of prenatal opiate exposure.

PMID- 15717853
TI  - Biological half-life of bromide in the rat depends primarily on the magnitude of
      sodium intake.
AB  - The parallel course of the excretion rates of bromide and sodium ions was
      demonstrated in adult male and female rats administered simultaneously with
      potassium 82Br-bromide and 24Na-sodium chloride. The animals were exposed to
      various intakes of sodium ions accompanied with five different anions: Br-, Cl-,
      HCO3-, ClO4-, and SCN-. Regardless of the anion accompanying the sodium ion, the
      excretion rates of 82Br- and 24Na+ ions were proportional to the magnitude of
      sodium intake in the animals. Hence, we have proved our hypothesis that the
      biological half-life of bromide depends on the magnitude of sodium intake rather
      than on the intake of chloride.

PMID- 15717854
TI  - Negative inotropic effect of insulin in papillary muscles from control and
      diabetic rats.
AB  - The inotropic effects of insulin in the rat heart are still incompletely
      understood. In this study, the effects of insulin on cardiac contraction were
      studied in right ventricular papillary muscles from both control rats and rats
      with chronic diabetes (lasting 16 weeks). Diabetes was induced by the application
      of streptozotocin (STZ) and the development of diabetes was documented by
      increased levels of blood glucose, by reduction in body weight and by decreased
      plasma concentrations of insulin. The contraction was significantly smaller in
      diabetic rats. Insulin (80 IU/l) reduced the contraction force in both control
      and diabetic groups. The post-rest potentiation of contraction was not influenced
      by insulin in control rats, but insulin increased it in diabetic rats. The
      negative inotropic effect of insulin was preserved in the presence of
      cyclopiazonic acid (3 micromol/l), a blocker of sarcoplasmic reticulum (SR) Ca2+
      pump, in both control and diabetic groups. In contrast, the negative inotropic
      effect of insulin was completely prevented in the presence of nifedipine (3
      micromol/l), a blocker of L-type Ca2+ current. We conclude that insulin exerts a
      significant negative inotropic effect in rat myocardium, both control and
      diabetic. This effect is probably related to processes of SR Ca2+ release
      triggering, whereas SR Ca2+ loading is not involved.

PMID- 15717855
TI  - Biochemical changes as enzymatic defense system of phenanthrene exposure in olive
      flounder, Paralichthys olivaceus.
AB  - The objective of this study was to investigate early biological response in olive
      flounder exposed to sub-lethal concentrations of waterborne phenanthrene (0.5, 1
      or 2 microM). The fish were exposed for 4 weeks and we analyzed their enzymatic
      defense system, antioxidant and phase II enzyme activities, to evaluate the
      chronic exposure toxicity of phenanthrene. Waterborne phenanthrene affected
      antioxidant enzymes and glutathione-mediated detoxification as enzyme defense
      system. Hepatic, gill and kidney glutathione reductase as well as glutathione S
      transferase, and catalase activities were markedly elevated after two or four
      weeks of exposure. These enzymes activities of olive flounder, Paralichthys
      olivaceus seem to be a convenient tool for monitoring pollution in coastal areas
      against PAHs pollution including phenanthrene.

PMID- 15717856
TI  - Differences in anxiety-related behavior between apolipoprotein E-deficient
      C57BL/6 and wild type C57BL/6 mice.
AB  - The influence of ApoE gene deletion on the anxiety state has not been previously
      investigated. The elevated plus maze was used in this study to determine
      differences in anxiety-related behavior between apoE-deficient and wild type
      C57BL/6 mice. The apoE-deficient mice demonstrated less anxiety on the elevated
      plus maze by spending more time in the open arms of the elevated plus maze
      compared to wild type mice (p<0.001). Additionally, female apoE-deficient mice
      visited the open arm of the maze more often than their apoE-deficient male
      counterpart (p<0.05). The anxiety state and/or sex are possible variables to be
      considered when designing physiological and/or behavioral studies involving mice
      that are apoE-deficient.

PMID- 15717857
TI  - The comparison of Ca2+/CaM-independent and Ca2+/CaM-dependent phosphorylation of
      myosin light chains by MLCK.
AB  - The main regulatory mechanism of smooth muscle contraction involves
      Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin (CDPM), by myosin light
      chain kinase (MLCK). It is also known that the increase in intracellular Ca2+ and
      phosphorylation of myosin occurs within a short time under physiological
      conditions, but the muscle tension may persist for a longer period of time.
      However, the mechanism of this phenomenon is still not clear. We hypothesize that
      MLCK also phosphorylates myosin in a Ca2+/CaM-independent manner (CIPM). The
      difference between CIPM and CDPM are as follows. Firstly, the extent of CIPM by
      MLCK was temperature-independent, whereas CDPM by MLCK was apparently decreasing
      with increasing temperature. Secondly, in contrast to the decreased extent of
      CDPM, the prolongation of incubation time did not decrease the extent of CIPM.
      Thirdly, a high concentration of K+ influences CIPM less than CDPM. Furthermore,
      the MLCK inhibitor ML-9 significantly inhibited CDPM by MLCK but not CIPM by
      MLCK. Lastly, arachidonic acid selectively increased CIPM by MLCK but not CDPM by
      MLCK. Finally, the activity of Mg2+-ATPase of myosin followed the sequence as
      this: CDPM>CIPM>unphosphorylated myosin. Our results revealed some primary
      features of CIPM by MLCK.

PMID- 15717858
TI  - Visual evoked potentials and event related potentials in congenitally deaf
      subjects.
AB  - The purpose was to test parameters of visual evoked potentials (VEPs) and of
      event-related potentials (ERPs) in deaf subjects to verify visual and cognitive
      CNS functions in a handicapped group of the population. Three types of visual
      stimuli (with dominating parvocellular or magnocellular system activation or with
      cognitive tasks) were used in the study. Six deaf persons (4 women, 2 men, mean
      age 17 years) and 6 persons with normal hearing (sex- and age-matched) were
      included in this pilot study. In all types of stimulation, latencies and
      amplitudes of main VEPs and ERPs components were evaluated. No significant
      latency differences were found. However, significantly reduced amplitudes were
      found in the occipital area for responses to motion and cognitive stimuli which
      might be interpreted as a part of functional reorganization of the extrastriate
      and cognitive cortical areas of deaf subjects.

PMID- 15717859
TI  - Relationship between maximal oxygen uptake and oxygenation level in inactive
      muscle at exhaustion in incremental exercise in humans.
AB  - The aim of the present study was to determine whether the oxygenation level in an
      inactive muscle during an incremental exercise test, determined by near-infrared
      spectroscopy, influences the maximal oxygen uptake (Vo2max). The oxygenation
      level at the onset of incremental exercise was higher than that at rest and
      started to decrease at a high power output. A minimal level was observed at
      exhaustion during incremental exercise. Vo2 increased linearly after some delay,
      and the rate of increase in Vo2 was greater at a higher power output. Heart rate
      increased linearly after the time delay, and the rate of increase in heart rate
      did not change. There was a significant correlation between Vo2max and
      oxygenation level in inactive muscle at exhaustion (r=-0.89). We therefore
      concluded that the oxygenation level in inactive muscle at exhaustion during
      incremental exercise is associated with an individual difference in Vo2max.

PMID- 15717860
TI  - Cough and laryngeal muscle discharges in brainstem lesioned anaesthetized cats.
AB  - Experiments were carried out to determine whether there are separate drives from
      the selected neuronal networks of the brainstem affecting the discharge patterns
      of laryngeal and respiratory pump muscles during cough. Twenty-four non
      decerebrate spontaneously breathing cats anesthetized with sodium pentobarbitone
      were used. Microinjections of kainic acid into the lateral tegmental field of the
      medulla, medullary midline or pontine respiratory group eliminated the cough
      evoked by mechanical stimulation of the tracheobronchial and laryngopharyngeal
      mucosa. These stimuli, in most cases, provoked irregular bursts of discharges in
      the posterior cricoarytenoid and thyroarytenoid laryngeal muscles (or they had no
      effect on them). No pattern of laryngeal muscle activities following lesions
      resembled the laryngeal cough response. Lesions of the target regions did not
      result in any apparent changes in the eupnoeic pattern of laryngeal activity.
      Neurons of the medullary lateral tegmental field, raphe nuclei and the pontine
      respiratory group seem to be indispensable for the configuration of the central
      cough motor pattern. However, these neurons do not appear to be essential for the
      discharge patterns of laryngeal motoneurons during eupnoea. The residual
      laryngeal "cough" responses are probably mediated by an additional motor drive.

PMID- 15717861
TI  - Maternal plasma VEGF, sVEGF-R1, and PlGF concentrations in preeclamptic and
      normotensive pregnant Zimbabwean women.
AB  - Vascular endothelial growth factor (VEGF), a disulphide-linked homodimeric
      glycoprotein that is selectively mitogenic for endothelial cells, plays an
      important role in vasculogenesis and angiogenesis. Preeclampsia, a relatively
      common complication of pregnancy that is characterized by diffuse endothelial
      dysfunction possibly secondary to impaired trophoblast invasion of the spiral
      arteries during implantation, has recently been associated with alterations in
      maternal serum/plasma concentrations of VEGF, and other related growth factors
      and their receptors. We examined the relationship of maternal plasma VEGF, sVEGF
      R1 and PlGF levels to the risk of preeclampsia among women delivering at Harare
      Maternity Hospital, Zimbabwe. 131 pregnant women with preeclampsia and 175
      controls were included in a case-control study. Maternal plasma concentrations of
      each biomarker were measured using enzymatic methods. We used logistic regression
      to calculate odds ratios (OR) and 95 % confidence intervals (CI). Preeclampsia
      risk was inversely related with quartiles of plasma VEGF (OR: 1.0, 1.0, 0.7, and
      0.5, with the lowest quartile as reference; p for trend=0.06). We noted a strong
      positive association between preeclampsia risk and sVEGF-R1 concentrations (OR:
      1.0, 6.5, 9.7, 31.6, with the first quartile as the referent group; p for
      trend<0.001). After adjusting for confounders, we noted that women with sVEGF-R1
      concentrations in the highest quartile (>or=496 pg/ml), as compared with those in
      the lowest quartile (<62 pg/ml) had a 31.6-fold increased risk of preeclampsia
      (OR=31.6, 95 % CI 7.7-128.9). There was no clear evidence of a linear relation in
      risk of preeclampsia with PlGF concentrations. In conclusion, plasma VEGF, sVEGF
      R1 and PlGF concentrations (measured at delivery) were altered among Zimbabwean
      women with preeclampsia as compared with normotensive women. Our results are
      consistent with some, though not all, previous reports. Prospective studies are
      needed to: 1) identify modifiable determinants of maternal plasma concentrations
      VEGF, sVEGF-R1, and PlGF; and 2) evaluate the temporal relationship between
      observed alterations of these biological markers in preeclamptic pregnancies.

PMID- 15717862
TI  - Antioxidant vitamin levels do not exhibit negative correlation with the extent of
      acute myocardial infarction.
AB  - Serum levels of vitamin E (VE), beta-carotene (BC) and vitamin C (VC) were
      determined in 50 patients with the first acute myocardial infarction (AMI) before
      starting thrombolytical treatment. VE and BC were determined by HPLC, VC
      spectrophotometrically. The reperfused patients were divided according to vitamin
      concentrations into four groups. The lowest quartile was compared with the rest
      of the studied population (VE: group with high (H)>15.6 microM>group with low
      (L), BC: H>0.07 microM>L, VC: H>25 microM>L) in the following parameters: extent
      of myocardial damage (area under the curves of troponin I, CK-MB during 48 h),
      arrhythmia and congestive heart failure occurrence, size of ejection fraction,
      positivity of ventricular late potentials. No significant differences between
      groups H and L for either VE, BC or VC were found (P 0.05). As no correlation
      between serum concentrations of vitamins E, C and beta-carotene and the extent
      and clinical course of AMI was found, the actual vitamin concentrations may be
      important for prevention of ischemic heart a disease, but they do not play a
      decisive role in the acute phase of myocardial infarction in humans.

PMID- 15717863
TI  - Relationship between hepatic phenotype and changes in gene expression in
      cytochrome P450 reductase (POR) null mice.
AB  - Cytochrome P450 reductase is the unique electron donor for microsomal cytochrome
      P450s; these enzymes play a major role in the metabolism of endogenous and
      xenobiotic compounds. In mice with a liver-specific deletion of cytochrome P450
      reductase, hepatic cytochrome P450 activity is ablated, with consequent changes
      in bile acid and lipid homoeostasis. In order to gain insights into the metabolic
      changes resulting from this phenotype, we have analysed changes in hepatic mRNA
      expression using microarray analysis and real-time PCR. In parallel with the
      perturbations in bile acid levels, changes in the expression of key enzymes
      involved in cholesterol and lipid homoeostasis were observed in hepatic
      cytochrome P450 reductase null mice. This was characterized by a reduced
      expression of Cyp7b1, and elevation of Cyp7a1 and Cyp8b1 expression. The levels
      of mRNAs for other cytochrome P450 genes, including Cyp2b10, Cyp2c29, Cyp3a11 and
      Cyp3a16, were increased, demonstrating that endogenous factors play a role in
      regulating the expression of these proteins and that the increases are due, at
      least in part, to altered levels of transcripts. In addition, levels of mRNAs
      encoding genes involved in glycolysis and lipid transport were also increased;
      the latter may provide an explanation for the increased hepatic lipid content
      observed in the hepatic null mice. Serum testosterone and oestradiol levels were
      lowered, accompanied by significantly decreased expression of Hsd3b2 (3beta
      hydroxy-Delta5-steroid dehydrogenase-2), Hsd3b5 (3beta-hydroxy-Delta5-steroid
      dehydrogenase-5) and Hsd11b1 (11beta-hydroxysteroid dehydrogenase type 1), key
      enzymes in steroid hormone metabolism. These microarray data provide important
      insights into the control of metabolic pathways by the cytochrome system.

PMID- 15717865
TI  - Molecular directionality in crystalline beta-chitin: hydrolysis by chitinases A
      and B from Serratia marcescens 2170.
AB  - Beta-chitin microfibrils were treated with ChiA and ChiB (chitinases A and B
      respectively) from Serratia marcescens 2170. The beta-chitin microfibrils were
      shortened, and the tips appeared narrowed and sharpened at both ends, after
      either consecutive or simultaneous degradation by ChiA and ChiB. Increased
      production of reducing sugars by simultaneous degradation (by ChiA and ChiB) of
      beta-chitin, but not of glycol chitin, suggests synergistic interactions between
      the two enzymes. A combined analysis using the tilt microdiffraction method to
      determine the crystallographic axes, together with the biotin-streptavidin-gold
      labelling method specific to the reducing ends, was used to investigate the
      polarity of the degraded beta-chitin microcrystals. The digestion of the beta
      chitin fibrils by ChiA occurred from the reducing end to the nonreducing end,
      whereas digestion by ChiB occurred from the non-reducing end to the reducing end.
      The results are in agreement with the previously determined three-dimensional
      structures of these enzymes.

PMID- 15717864
TI  - Identification, characterization and structure of a new Delta class glutathione
      transferase isoenzyme.
AB  - The insect GST (glutathione transferase) supergene family encodes a varied group
      of proteins belonging to at least six individual classes. Interest in insect GSTs
      has focused on their role in conferring insecticide resistance. Previously from
      the mosquito malaria vector Anopheles dirus, two genes encoding five Delta class
      GSTs have been characterized for structural as well as enzyme activities. We have
      obtained a new Delta class GST gene and isoenzyme from A. dirus, which we name
      adGSTD5-5. The adGSTD5-5 isoenzyme was identified and was only detectably
      expressed in A. dirus adult females. A putative promoter analysis suggests that
      this GST has an involvement in oogenesis. The enzyme displayed little activity
      for classical GST substrates, although it possessed the greatest activity for DDT
      [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] observed for Delta GSTs.
      However, GST activity was inhibited or enhanced in the presence of various fatty
      acids, suggesting that the enzyme may be modulated by fatty acids. We obtained a
      crystal structure for adGSTD5-5 and compared it with other Delta GSTs, which
      showed that adGSTD5-5 possesses an elongated and more polar active-site topology.

PMID- 15717867
TI  - Foot temperature in diabetic polyneuropathy: innocent bystander or unrecognized
      accomplice?
AB  - AIM: To explore mechanisms by which temperature could influence the pathogenesis
      and symptoms of diabetic polyneuropathy. METHODS: We conducted a literature
      review attempting to identify mechanisms by which diabetic polyneuropathy could
      be affected by temperature. RESULTS: Cooling can theoretically hasten the
      progression of diabetic polyneuropathy through several different mechanisms.
      Specifically, cooling can enhance neuronal ischaemia, increase formation of
      reactive oxygen species, slow axonal transport, increase protein kinase C
      activity, and interfere with immune function. Short-term temperature fluctuations
      (both warming and cooling) can initiate and exacerbate neuropathic pain by
      causing neuronal hyperexcitability and functional deafferentation. Although
      normal fluctuations of distal extremity temperature may be sufficient for these
      effects, impaired thermoregulation may make the distal extremities more
      susceptible to temperature extremes. Eventually, a 'vicious cycle' may ensue,
      resulting in neuronal deterioration with further disruption of temperature
      regulation. Limited epidemiological data suggest a higher prevalence of diabetic
      polyneuropathy in populations living in colder locations, supporting our
      hypothesis. CONCLUSIONS: Variations in foot temperature may play an important but
      as yet unrecognized role in the development and symptoms of diabetic
      polyneuropathy. Further basic and clinical research exploring this concept could
      help elucidate the natural history of diabetic polyneuropathy and lead to novel
      therapeutic strategies.

PMID- 15717866
TI  - Splice variants of the cyclic nucleotide phosphodiesterase PDE4D are
      differentially expressed and regulated in rat tissue.
AB  - Cyclic nucleotide PDE4 (phosphodiesterase 4) inhibitors are being developed as
      potent anti-inflammatory drugs for use in chronic lung diseases, but the
      complexity of the PDE4 family has hampered this process. The four genes
      comprising the PDE4 family, PDE4A, PDE4B, PDE4C and PDE4D, are all expressed as
      multiple splice variants. The most widely used criterion to identify PDE4
      variants expressed endogenously is their migration on SDS/PAGE. However, when a
      PDE4D3-selective antibody was used for immunoprecipitation, the pattern of
      expression obtained did not confirm the expression predicted by SDS/PAGE. This
      observation, together with the recent discovery of additional PDE4D transcripts,
      prompted us to re-evaluate the pattern of expression of these variants. The nine
      rat PDE4D splice variants, PDE4D1 to PDE4D9, were cloned, their electrophoretic
      properties compared, and their in vivo mRNA and protein levels determined. Using
      this approach, we found that the pattern of distribution of the PDE4D splicing
      variants is more complex than previously reported. Multiple variants co-migrate
      in single immunoreactive bands, and variant-selective antibodies were necessary
      to discriminate between splice variants. Tissues that were thought to express
      only PDE4D3, express three closely related proteins, with PDE4D8 and PDE4D9 as
      the predominantly expressed forms. In addition, activation of cAMP signalling
      produces phosphorylation and activation of variants other than PDE4D3, and
      expression of PDE4D mRNA does not always correlate with the pattern of protein
      expression. As PDE4 inhibitors have different affinities for distinct PDE4D
      splicing variants, our results indicate that a better definition of the pattern
      of PDE4 expression is required for target validation.

PMID- 15717868
TI  - Statin therapy improves brachial artery vasodilator function in patients with
      Type 1 diabetes and microalbuminuria.
AB  - AIMS: Type 1 diabetes mellitus patients with microalbuminuria have endothelial
      dysfunction associated with the degree of albuminuria but not with LDL
      cholesterol levels. Lipid-lowering agents such as statins may still be of benefit
      as they can correct endothelial dysfunction by both lipid and non-lipid
      mechanisms. We therefore examined the effects of atorvastatin on brachial artery
      endothelial dysfunction in these patients. METHODS: In a double-blind, randomized
      crossover study, 16 Type 1 diabetes mellitus patients with microalbuminuria
      received 6 weeks of atorvastatin 40 mg/day or placebo, separated by a 4-week
      washout. Brachial artery, endothelium-dependent, flow-mediated dilatation (FMD)
      and endothelium-independent, glyceryl trinitrate-mediated dilatation (GTNMD) were
      measured. RESULTS: Compared with placebo, atorvastatin produced a significant
      decrease in apolipoprotein B (34.2%), LDL-cholesterol (44.1%) (all P < 0.001),
      and oxidized-LDL (35.7%, P = 0.03). There was a non-significant increase in
      plasma cGMP (P = 0.13) on atorvastatin. FMD and GTNMD increased significantly on
      atorvastatin (FMD: atorvastatin +1.8 +/- 0.4%; placebo +0.2 +/- 0.4%, P = 0.007);
      (GTNMD: atorvastatin +1.3 +/- 0.9%; placebo -1.2 +/- 0.6%, P = 0.04). An increase
      in cGMP was independently correlated with an increase in FMD on atorvastatin
      (adjusted (R2) 0.41, P = 0.02). CONCLUSION: Atorvastatin improves endothelium
      dependent and independent vasodilator function of the brachial artery in Type 1
      diabetes mellitus patients with microalbuminuria. This may relate to pleiotropic
      effects of statins, in particular reduced oxidative stress and increased
      availability of nitric oxide.

PMID- 15717869
TI  - The J-shape effect of alcohol intake on the risk of developing acute coronary
      syndromes in diabetic subjects: the CARDIO2000 II Study.
AB  - AIMS: To identify the threshold of alcohol consumption above which the balance of
      risk and benefit becomes adverse in diabetic subjects. METHODS: We studied
      demographic, lifestyle, dietary and clinical information in 216 hospitalized
      diabetic patients (171 men, 63 +/- 9 years old, 45 women, 67 +/- 5 years old)
      with a first event of an acute coronary syndrome (ACS) and 196 frequency matched
      (age-sex) diabetic controls, without any clinical evidence of coronary heart
      disease. Alcohol consumption was quantified and a measure for the comparisons was
      predetermined to be a wine glass (100 ml of wine, 12 g of ethanol) and its
      alcohol equivalents. RESULTS: Alcohol consumption was associated with an age
      adjusted J-shape relationship with total cholesterol, blood pressure and smoking
      (all P < 0.001). A J-shape association was also found between alcohol intake and
      the risk of ACS (OR = 2.54-2.43 x (alcohol intake) + 0.80 x (alcohol intake)2, R2
      = 0.96, P < 0.001), adjusted for several risk factors and interactions between
      alcohol intake and smoking status, job and familial stress, and low income. In
      particular, low alcohol consumption (< 12 g/day) was associated with a 47% (OR =
      0.53, 95% CI 0.28-0.97) reduction of the prevalence of ACS, while a higher intake
      (12-24 and > 24 g/day) increased the prevalence by 2.7-fold (OR = 2.72, 95% CI
      1.39-5.38) and 5.4-fold (OR = 5.44, 95% CI 1.21-24.55), respectively.
      CONCLUSIONS: Alcohol intake is a significant predictor of coronary events. Low-to
      moderate intake seems to be associated with a reduction in the prevalence of ACS
      in diabetes, whereas higher consumption is associated with an increase in lipids
      and blood pressure levels, and also the risk of developing ACS.

PMID- 15717870
TI  - The effect of multi-factorial intervention on plasma von Willebrand factor,
      soluble E-selectin and tissue factor in diabetes mellitus: implications for
      atherosclerotic vascular disease.
AB  - BACKGROUND: Endothelial abnormalities and a hypercoagulable state may contribute
      to increased cardiovascular risk in diabetes mellitus, particularly in patients
      with overt cardiovascular disease (CVD). We sought to determine the effect of
      intensified multi-factorial cardiovascular risk intervention on indices of
      endothelial abnormality and hypercoagulability in diabetes, and if patients with
      overt CVD would derive similar benefit as those without. PATIENTS AND METHODS: We
      measured plasma von Willebrand factor (vWf, an index of endothelial
      damage/dysfunction), soluble E-selectin (sE-sel, marking endothelial activation)
      and tissue factor (TF, an initiator of coagulation) by ELISA in 94 patients with
      diabetes mellitus (38 with CVD and 56 without overt CVD) and 34 comparable
      controls. Thirty-three patients with CVD and 31 without overt CVD then
      participated in multi-factorial cardiovascular risk intervention over 1 year.
      RESULTS: Plasma levels of vWf (P = 0.009), sE-sel (P < 0.001) and TF (P < 0.001)
      were significantly higher in diabetic patients compared with controls, with TF
      highest in patients with overt CVD. Intensive multi-factorial intervention
      resulted in reductions in glycated haemoglobin (HbA(1c)), total and LDL
      cholesterol (all P < 0.05), but no significant weight change. This was associated
      with reductions in vWf in patients with (by 26%P = 0.003), and without (by 47%, P
      < 0.001), overt CVD. TF was reduced only in patients without overt CVD (by 45%, P
      < 0.001). There were no significant changes in sE-sel levels in either group.
      CONCLUSION: Endothelial abnormalities in diabetes are only partially influenced
      by contemporary intensified multi-factorial cardiovascular risk intervention.
      These data suggest the need for earlier and more aggressive risk factor
      intervention.

PMID- 15717871
TI  - A mobile screening programme for the cardiovascular and microvascular
      complications of Type 2 diabetes in primary care.
AB  - The Diabetes National Service framework (NSF), and the quality payments in the
      new contract for UK General Practitioners, promote regular screening for diabetes
      complications. The new contract also includes immediate incentives to meet
      screening and quality targets, but it will be difficult to meet these targets in
      primary care. We have developed a mobile 'annual review' programme for patients
      with Type 2 diabetes managed solely in primary care, that screens for
      cardiovascular disease, hypertension, retinopathy and neuropathy at the patient's
      general practice, and gives written foot care, dietary advice and level 1 smoking
      cessation advice to all patients.

PMID- 15717872
TI  - Renal damage in patients with Type 2 diabetes: a strong predictor of mortality.
AB  - AIMS: (i) To compare mortality rates in a cohort of Type 2 diabetic patients with
      those of the general population; (ii) to assess the prognostic role of pre
      existing chronic conditions; (iii) to evaluate the impact of different severity
      of renal damage on mortality. METHODS: All 3892 patients with Type 2 diabetes
      attending our Diabetic Clinic during 1995 and alive on 1 January 1996 were
      identified and followed for 4.5 years. Information on vital status (100%
      complete) and causes of death (98.5% complete) for 599 deceased subjects was
      derived from death certificates. RESULTS: In comparison with the general
      population, standardized mortality ratios (x 100) were: 125 (95% confidence
      interval 104-148) in patients aged < 75 and 85 (75-95) in patients > or = 75
      years. Cardiovascular diseases and diabetes were responsible for most of the
      excess deaths. In a Cox-proportional hazard model, renal damage was a powerful
      predictor of death (hazard ratio = 2.39; 95% confidence intervals = 2.00-2.85).
      The severity of renal damage was associated with increasing hazard ratios for
      death from all-cause mortality and from specific causes (especially coronary
      artery disease, other cardiovascular causes and diabetes) after multiple
      adjustments. Other significant predictors of death were: greater age, glycated
      haemoglobin, smoking, lower body mass index, pre-existing coronary and peripheral
      artery disease and known co-morbidity (cirrhosis and cancer). CONCLUSIONS: Renal
      damage of any severity is significantly associated with subsequent mortality from
      all causes and from cardiovascular diseases. These associations are not
      confounded by pre-existing co-morbidity or coronary diseases.

PMID- 15717873
TI  - Greater beneficial effects of visceral fat reduction compared with subcutaneous
      fat reduction on parameters of the metabolic syndrome: a study of weight
      reduction programmes in subjects with visceral and subcutaneous obesity.
AB  - AIMS: To evaluate the effect of weight reduction on parameters of the metabolic
      syndrome in obese patients according to their pattern of abdominal fat
      distribution. METHODS: A longitudinal intervention study, consisting of a 12-week
      weight reduction programme, including lifestyle modification and adjuvant
      appetite suppressant, in 38 subjects with visceral obesity and 47 subjects with
      subcutaneous obesity. Visceral, subcutaneous and total adipose tissue areas were
      determined by CT scan at the level of L4-L5. Parameters for components of the
      metabolic syndrome were measured before and after weight reduction. RESULTS:
      Reductions in body weight, BMI and subcutaneous adipose tissue area were greater
      in the subcutaneous than in the visceral obesity group. In contrast, changes in
      fasting plasma glucose, insulin, and HOMA score were higher in the visceral than
      in the subcutaneous obesity group. Changes in visceral adipose tissue area were
      significantly related to changes in fasting plasma glucose, triglycerides and
      HOMA score. CONCLUSIONS: Visceral fat reduction induced greater beneficial
      effects on parameters of the metabolic syndrome than subcutaneous fat reduction.
      Evaluation of changes in abdominal fat distribution is necessary when obese
      subjects enter a weight reduction programme.

PMID- 15717874
TI  - Pharmacokinetic profiles of biphasic insulin aspart 30/70 and 70/30 in patients
      with Type 1 diabetes: a randomized double-blinded crossover study.
AB  - AIMS: To compare pharmacokinetic characteristics of two biphasic insulin aspart
      (BIAsp) formulations: BIAsp30 and BIAsp70 (30% and 70%, respectively, of fast
      acting insulin aspart) during 15 days of multiple dosing (thrice daily). METHODS:
      A total of 22 patients with Type 1 diabetes (nine women, 13 men) aged 41.4 +/-
      9.9 years (mean +/- sd) with a diabetes duration of 18.9 (2.3-40.3) years (median
      and range) completed the randomized, double-blinded, two-period crossover study.
      On day 1 and day 15 of each treatment period, 24-h serum insulin and glucose
      profiles were evaluated. Total area under the insulin aspart concentration-time
      curve (AUC(0-24 h)), AUC after dinner administration stratified into early
      (AUCdinner(0-6 h)) and intermediate-phase (AUCdinner(6-14 h)), maximum insulin
      concentration (Cmax), time to maximum insulin concentration (Tmax) after each
      meal were recorded. RESULTS: On day 15 BIAsp70 was associated with a shorter
      Tmax, and more than 40% elevated Cmax. Comparing with BIAsp30, AUC(0-24 h) and
      AUCdinner(0-6 h) were increased by 25% and 28%, respectively, but AUCdinner (6-14
      h) was markedly lower for BIAsp70 [BIAsp30/BIAsp70: 1.9; 95% CI (1.42, 2.55)].
      Similar findings were also observed on day 1. The fasting or pre-meal serum
      insulin levels on day 15 tended to be higher with BIAsp30, but the differences
      were not statistically significant. CONCLUSIONS The pharmacokinetic properties of
      BIAsp30 and 70 remain constant during 2 weeks of daily administration in patients
      with Type 1 diabetes. In comparison with BIAsp30, the administration of BIAsp70
      results in a shorter time to and larger maximum insulin aspart concentration.
      Furthermore, total and early post-dinner insulin AUC were greater, whereas late
      phase insulin exposure was lower with BIAsp70.

PMID- 15717875
TI  - Plasma leptin concentration in patients with Type 2 diabetes: relationship to
      cardiovascular disease risk factors and insulin resistance.
AB  - AIMS: The aim of this study was to evaluate the relationship of obesity, leptin,
      insulin resistance and C-reactive protein (CRP) with coronary heart disease (CHD)
      risk factors in patients with Type 2 diabetes mellitus (DM) with CHD compared
      with those with Type 2 DM without CHD. METHODS: Leptin, CRP (high sensitivity
      assay), fasting plasma insulin, glucose, HbA(1c) and full lipid profile were
      determined in 58 Type 2 diabetic patients with CHD and 87 Type 2 DM patients
      without CHD. RESULTS: were compared between those with and without CHD.
      Univariate correlation as well as logistic regression analyses were used to
      relate these markers with traditional CHD risk factors. RESULTS: Leptin showed
      significant correlations with BMI (r = 0.59; P < or = 0.0001), waist
      circumference (r = 0.45; P < 0.0001), CRP (r = 0.36; P < 0.0001), and fasting
      insulin (r = 0.53; P < 0.0001) as well as with systolic (r = 0.23; P = 0.007) and
      diastolic (r = 0.23; P = 0.007) blood pressure. However, when those with and
      without CHD were compared only age (P < 0.0001), duration of diabetes (P < 0.001)
      and degree of microalbuminuria (P = 0.02) were significantly higher in patients
      with CHD. Leptin (P = 0.49), CRP (P = 0.19) and lipid parameters were not
      significantly different between the two groups. CONCLUSION: Our study confirms a
      relationship between leptin and CRP with CHD risk factors. The lack of
      significant difference when patients with and without CHD are compared may be due
      to the potential confounding effects of treatment with aspirin and statins.

PMID- 15717876
TI  - How diabetic patients think about and manage their illness in Taiwan.
AB  - AIMS: Type 2 diabetes is becoming more prevalent in Taiwan. Growing evidence
      suggests a patient-centred approach is more effective in facilitating self
      management than a professional-centred one. The aim of this qualitative study was
      to investigate Chinese diabetic patients' perceptions about their illness and
      treatment strategies to facilitate patient-centred, culture-sensitive clinical
      skills. METHODS: We used in-depth interviews to collect perspectives from 22
      participants recruited from a rural Taiwan community. All interviews were audio
      taped and the transcripts were analysed by editing and immersion/crystallization.
      Emerging themes were compared with current medical knowledge to determine their
      clinical significance. RESULTS: Generally, Chinese diabetic patients had variable
      perceptions about different treatment strategies. All agreed that dietary
      restriction and exercise were beneficial. The former, mainly understood as
      reducing carbohydrate intake, was thought to be most important; exercise, to the
      point of sweating, was seen as a way to eliminate pharmaceutical toxins. Taking
      medicine was regarded with ambivalent attitudes due to concerns about adverse
      effects (especially renal injury). CONCLUSIONS: Patients regarded all treatment
      strategies as integrative and intertwined in daily life. There are three
      misconceptions which we found should be clarified during medical consultations:
      (i) focusing on sugar-control only; (ii) benefit of sweating to eliminate toxins;
      (iii) fear of renal toxicity of hypoglycaemic agents. The renaming of diabetes,
      to such as 'metabolic syndrome', may bring new, acceptable insight to Chinese
      diabetic patients.

PMID- 15717877
TI  - Affective and anxiety disorders in a German sample of diabetic patients:
      prevalence, comorbidity and risk factors.
AB  - AIMS: The aims of this study were to examine (1) the prevalence of clinical and
      subclinical anxiety and affective disorders in a sample of diabetic patients
      attending a secondary care clinic in Germany and (2) risk factors associated with
      the occurrence of these disorders. METHODS: Four hundred and twenty diabetic
      patients (36.9% Type 1; 24.7% Type 2; 38.4% Type 2 with insulin) participated in
      a questionnaire-based screening survey. Those who screened positive received a
      diagnostic interview. RESULTS: Prevalence of clinical affective disorders was
      12.6%, with an additional 18.8% of patients reporting depressive symptoms without
      fulfilling all criteria for a clinical affective disorder. The prevalence of
      anxiety disorders was 5.9%, with an additional 19.3% of patients reporting some
      anxiety symptoms. The comorbidity rate of affective and anxiety disorders was
      1.8%, whereas 21.4% of the diabetic patients reported elevated affective as well
      as anxiety symptomatology. Logistic regression established demographic variables
      such as age, female gender and living alone as well as diabetes-specific
      parameters such as insulin treatment in Type 2 diabetes, hypoglycaemia problems
      and poor glycaemic control as risk factors for affective disorders. For anxiety
      symptoms female gender, younger age and Type 2 diabetes were significant
      independent variables. CONCLUSION: The prevalence of affective disorders in
      diabetic patients was twofold higher than in the non-diabetic population, whereas
      prevalence for anxiety disorders was not increased. Analysis of risk factors can
      facilitate the identification of patients who are at a greater risk for these
      disorders.

PMID- 15717878
TI  - Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is
      determined by increased renal clearance.
AB  - INTRODUCTION: Elevated plasma levels of total homocysteine are related to the
      development of vascular complications. Patients with diabetes mellitus are
      particularly at risk for the development of these complications. Several factors
      determine plasma total homocysteine including renal function. AIMS: As early Type
      1 diabetes is characterized by a relative glomerular hyperfiltration, increased
      renal clearance could contribute to decreased levels of homocysteine as observed
      in Type 1 diabetes mellitus. Therefore we investigated the relationship between
      plasma total homocysteine and the glomerular filtration rate (GFR). METHODS: In
      92 Type 1 diabetes patients and 44 control subjects, we measured GFR and
      effective renal plasma flow (ERPF) by means of continuous infusion of inulin and
      p-aminohippurate. Fasting plasma total homocysteine was measured using high
      performance liquid chromatography. RESULTS: GFR (121 +/- 21 resp. 104 +/- 14
      ml/min; P < 0.001) and ERPF (563 +/- 127 resp. 516 +/- 121 ml/min; P = 0.05) were
      significantly higher in Type 1 diabetes patients as compared with control
      subjects. Plasma total homocysteine was reduced in Type 1 diabetes patients as
      compared with control subjects (11.0 +/- 4.5 resp. 13.4 +/- 7 micromol/l; P =
      0.01). Plasma total homocysteine was strongly correlated with GFR (Type 1
      diabetes patients: r = -0.43, P < 0.001; control subjects: r = -0.39, P = 0.01).
      CONCLUSION: GFR is a major determinant of plasma total homocysteine levels in
      Type 1 diabetes patients as well as control subjects. The reduced plasma total
      homocysteine levels in diabetes patients can be explained by an increased GFR.

PMID- 15717880
TI  - Caries risk assessment as a predictor of metabolic control in young Type 1
      diabetics.
AB  - AIMS: To investigate the relationship between caries risk and glucosylated
      haemoglobin and to evaluate the use of a computerized caries risk assessment
      program as a predictor of metabolic control in schoolchildren with Type 1
      diabetes mellitus. METHODS: The material consisted of 64 young Type 1 diabetes
      mellitus patients (8-16 years) attending an outpatient paediatric clinic. Within
      2 weeks after the onset of diabetes, a caries risk assessment was carried out
      with the aid of a computer-based program (Cariogram) and data on the level of
      metabolic control were collected from the medical records at the 3-year check-up.
      Caries increment was registered at recall clinical examinations. RESULTS: A
      statistically significant positive relationship between caries risk and metabolic
      control was found (r = 0.51; P < 0.01), with a sevenfold increased risk of
      impaired metabolic control after 3 years in those assessed with high caries risk
      at onset (OR 7.3; P < 0.01). When the Cariogram was used as a predictor for the
      metabolic state of the disease, the sensitivity and specificity was 75% and 71%,
      respectively. The negative predictive value was 91%. CONCLUSIONS: Our data
      suggested that a caries risk assessment at the diagnosis of diabetes mellitus in
      children may be a good indicator of overall health care that can provide useful
      prognostic information on the level of metabolic control after 3 years.

PMID- 15717879
TI  - Insulin sensitivity at diagnosis of Type 2 diabetes is not associated with
      subsequent cardiovascular disease (UKPDS 67).
AB  - AIMS: Insulin resistance is common in Type 2 diabetes which, in turn, is
      associated with a markedly increased risk of cardiovascular disease. Whether
      insulin sensitivity measured after diagnosis of diabetes is associated with
      incident cardiovascular disease was evaluated in this prospective study. METHODS:
      Three thousand five hundred and eighty-two subjects with newly diagnosed
      diabetes, recruited to the UK Prospective Diabetes Study (UKPDS), free of
      cardiovascular disease, and with complete information on insulin sensitivity and
      potential confounders, were followed prospectively to the first occurrence of (i)
      fatal or non-fatal myocardial infarction, MI (ii) fatal or non-fatal stroke, and
      (iii) coronary heart disease, CHD (fatal or non-fatal MI, sudden death or
      ischaemic heart disease). Insulin sensitivity was measured by Homeostatic Model
      Assessment (HOMA). RESULTS: Insulin sensitivity as measured by HOMA was not
      associated with subsequent MI, stroke, or CHD in univariate or multivariate
      models controlling for age, sex, ethnicity, HbA(1c), body mass index, plasma
      triglycerides, cholesterol and smoking. The hazard ratio associated with a
      doubling of insulin sensitivity with fatal or non-fatal MI in a multivariate
      model was 0.92 (95% confidence interval, CI, 0.80-1.05). These results were not
      changed by the exclusion of overweight patients randomized to metformin.
      DISCUSSION: Estimation of insulin sensitivity provides no additional useful
      information with respect to the risk of the first occurrence of cardiovascular
      disease in patients with newly diagnosed Type 2 diabetes. Among patients with
      Type 2 diabetes, insulin resistance is not a risk factor for cardiovascular
      disease.

PMID- 15717881
TI  - An intensified lifestyle intervention programme may be superior to insulin
      treatment in poorly controlled Type 2 diabetic patients on oral hypoglycaemic
      agents: results of a feasibility study.
AB  - AIMS: The aims of this study were to assess whether, in Type 2 diabetic patients
      with inadequate glycaemic control on oral hypoglycaemic agents (OHA), a lifestyle
      intervention programme based on exercise and diet counselling (i) was as
      effective as insulin treatment in controlling blood glucose, and (ii) could
      prevent the weight gain usually accompanying the introduction of insulin
      treatment. METHODS: Thirty-eight Type 2 diabetic subjects treated with OHA,
      HbA(1c) 8-10.5% and body mass index (BMI) 26-40 kg/m2, were randomized to the
      following treatments: (i) lifestyle intervention (L), (ii) lifestyle intervention
      + insulin treatment (L+I) and (iii) insulin treatment alone (I). RESULTS: There
      was a reduction in HbA(1c) of -1.2 (interquartile range 1.0), -1.0 (1.7) and -1.5
      (2.5)% in group L, L+I and I, respectively, and all treatment groups achieved
      beneficial changes in blood lipid variables. There was no significant difference
      between the groups in the change observed in levels of HbA(1c) between start and
      12 months of treatment (P = 0.74). There was a significant difference in weight
      changes between groups (P < 0.01): group L reduced weight by median -3.0 (4.0)
      kg, groups L+I and I increased weight by 3.5 (3.4) and 4.9 (6.9) kg,
      respectively. CONCLUSIONS: Lifestyle intervention was as effective as insulin
      treatment in improving glycaemic control in poorly controlled subjects with Type
      2 diabetes, and resulted in weight loss during the intervention year. However,
      glycaemic control deteriorated and body weight increased in the lifestyle
      intervention group 1 year after the intervention stopped.

PMID- 15717882
TI  - Alcohol consumption and other risk factors for self-reported diabetes among
      middle-aged Japanese: a population-based prospective study in the JPHC study
      cohort I.
AB  - AIMS: Few prospective studies have examined the relationship between lifestyle
      characteristics and the incidence of diabetes mellitus in an Asian general
      population. This study was undertaken to evaluate the risk factors for Type 2
      diabetes in a population-based prospective study of middle-aged Japanese.
      METHODS: We investigated 12,913 men and 15,980 women, aged 40-59 years at
      baseline (year 0), who participated in the Japan Public Health Center-based
      prospective study on cancer and cardiovascular diseases (JPHC Study) Cohort I.
      The participants were followed for up to 10 years. Incident cases of diabetes
      were identified by self-reporting of a physician's diagnosis on two
      questionnaires sent to each participant, one at year 5 and the second at year 10.
      RESULTS: During the 10-year follow-up, 703 men and 482 women reported newly
      diagnosed diabetes. Age, body mass index (BMI), family history of diabetes and
      cigarette smoking were independent risk factors in both genders by multivariate
      analysis. Among men with a BMI < or = 22 kg/m2, a significant positive
      association was observed between the diabetes incidence and moderate (23.0 < 46.0
      g/day) to high (> 46.0 g/day) alcohol consumption, odds ratio 1.91 (95% CI, 1.05
      3.46) and 2.89 (1.63-5.11), respectively. Among men with a BMI > 22 kg/m2, a
      small non-significant increase in odds ratio was observed with alcohol
      consumption. CONCLUSIONS: Established risk factors for diabetes in western
      populations were also identified as predictors of the disease among Japanese.
      Moderate to high alcohol consumption was positively associated with the incidence
      of diabetes in Japanese lean (BMI < or = 22 kg/m2) men.

PMID- 15717883
TI  - A comparison of urinary albumin excretion rate and microalbuminuria in various
      glucose tolerance subjects.
AB  - AIMS: To investigate the difference of urinary albumin excretion rate (UAER) and
      microalbuminuria (MAU) in various glucose tolerance subjects, especially between
      isolated-impaired glucose tolerance subjects and isolated-impaired fasting
      glycaemia subjects. METHODS: A total of 2934 subjects were divided into five
      groups with various glucose tolerances, based on a 75-g oral glucose tolerance
      test. Microalbuminuria was defined when urinary albumin excretion rate was
      between 20 and 200 microg/min. RESULTS: (i) The UAER in the newly diagnosed Type
      2 diabetes mellitus group, impaired glucose tolerance/impaired fasting glycaemia
      group and isolated-impaired glucose tolerance group were all higher than that in
      the isolated-impaired fasting glycaemia group and normal glucose tolerance group,
      but it was comparable between isolated-impaired fasting glycemia group and normal
      glucose tolerance group. The prevalence of MAU and the odds ratio for MAU with
      adjustment for age and sex in various glucose tolerance groups showed the same
      trend as the UAER. (ii) After adjusting for age and sex, there is a significant
      association between logUAER and independent risk factors (partial correlation
      coefficients: r = 0.26 for 2-h post-challenge blood glucose, r = 0.26 for
      systolic blood pressure, r = 0.27 for diastolic blood pressure, r = 0.27 for body
      mass index and r = -0.13 for high density lipoprotein-cholesterol, all P <
      0.001). The risks for MAU were 2-h post-challenge blood glucose, body mass index
      and diastolic blood pressure, while high density lipoprotein-cholesterol was
      protective. CONCLUSIONS: The urinary albumin excretion rate and prevalence of
      microalbuminuria were higher in isolated-impaired glucose tolerance subjects than
      those in isolated-impaired fasting glycaemia subjects. At early abnormal glucose
      tolerance stage, the increasing post-challenge glycaemia might be a more
      important risk factor for urinary albumin excretion rate and microalbuminuria
      than increasing fasting glycaemia.

PMID- 15717885
TI  - Hepatitis C virus infection-related Type 1 diabetes mellitus.
AB  - BACKGROUND: Hepatitis C virus (HCV) has been associated with Type 2 diabetes
      mellitus, and many other viral infections have been associated with Type 1
      diabetes mellitus (Type 1 DM). An association between HCV and Type 1 DM, however,
      has never been reported. We report the case of a 66-year-old man who developed
      Type 1 DM 1 year after a blood transfusion-related HCV infection. Testing of
      serum specimens obtained in the weeks following blood transfusion demonstrated
      evidence of both acute HCV infection and development of Type 1 DM-related
      autoantibodies. CASE REPORT: A 66-year-old Taiwanese male received blood
      transfusions during coronary artery bypass surgery in 1987. Serum specimens,
      obtained as part of a study on post-transfusion hepatitis, demonstrated that the
      patient had no evidence of hepatitis C prior to transfusion, but developed acute
      HCV infection after transfusion. One year later, the patient, who had no personal
      or family history of diabetes, presented with diabetic ketoacidosis, and tests
      for C-peptide confirmed that he had Type 1 DM. Testing of pre- and post-operative
      serum specimens demonstrated that the patient developed positive tests for islet
      cell and glutamic acid decarboxylase antibodies 4 weeks after transfusion,
      concurrent with the development of acute HCV infection. CONCLUSIONS: The
      simultaneous development of HCV infection and diabetes-related autoantibodies
      suggest a relationship between HCV and Type 1 DM.

PMID- 15717884
TI  - Routine diagnosis of Type 2 diabetes mellitus in general practice and hospitals:
      how do patients differ?
AB  - OBJECTIVE: To study how Type 2 diabetic patients diagnosed by routine case
      finding in primary care differ from patients diagnosed in secondary care with
      regard to clinical characteristics, symptom-burden and prevalence of
      complications. RESEARCH DESIGN AND METHODS: A Danish population-based sample of
      1633 newly diagnosed Type 2 diabetic patients, of whom we had detailed
      information of sociodemographic and clinical characteristics, biochemical
      measurements, and complications among 1381. Blood and urine analyses were
      centralized. RESULTS: Of the patients, 76.8% were diagnosed in general practice.
      Compared with those diagnosed in secondary care, patients diagnosed in general
      practice on average had higher levels of cardiovascular risk factors (BMI: 29.8
      vs. 28.5 kg/m2, P < 0.001; systolic blood pressure: 149.4 vs. 143.2 mmHg, P <
      0.001; diastolic blood pressure: 85.2 vs. 82.5 mmHg, P < 0.001; haemoglobin
      A(1c): 10.1 vs. 8.4%, P < 0.0001; total cholesterol: 6.4 vs. 6.1 mmol/l, P <
      0.01), more frequently presented with hyperglycaemic symptoms (80.1 vs. 63.4%, P
      < 0.0001), while fewer had macrovascular complications (28.5 vs. 43.6%, P <
      0.0001). CONCLUSIONS: Judged from their risk profile, Type 2 diabetic patients
      diagnosed in primary care are at no less risk of developing diabetic
      complications than those diagnosed in secondary care.

PMID- 15717886
TI  - Improvement of glycaemic control with rebound following orlistat initiation and
      cessation associated with minimal weight change.
AB  - A 57-year-old Caucasian woman with Type 2 diabetes treated for seven years with
      diet and oral combination hypoglycaemic therapy was referred because of the
      progressive deterioration of glycaemic control. She was obese (77 kg, BMI =
      39.9), hypertensive, hypercholesterolaemic with marked osmotic symptoms (HbA(1c)
      12.2%), therefore she was started on insulin (Human Mixtard 30 b.d.) with
      metformin therapy. Dietary counselling, recommendations to increase physical
      activity, and supervised self-injection technique with titration of her insulin
      were also provided. She was routinely followed-up to assess her progress. Two
      years later, her glycaemic control remained suboptimal. Average HbA(1c) was 10.4%
      despite an increasingly high dose of insulin (94 units/day) although it improved
      when metformin was increased to 1 g t.d.s. (HbA(1c) = 9.3%). Her BMI
      progressively rose from 39.9 to 42.1 (77 to 82.5 kg) despite dietary advice. A
      trial of orlistat (three months) was commenced, after intensive dietary
      counselling, that reduced her body weight by 1.5 kg (2% reduction, BMI 41.3).
      However, her HbA(1c) improved by 0.5% (from 9.3 to 8.8%). Six months after
      orlistat was stopped her HbA(1c) rose to 10.5% and weight increased to 81.8 kg
      (BMI 41.8). Despite the orlistat treatment broaching NICE guidelines should it
      have been continued?

PMID- 15717887
TI  - Low-dose metformin improves hyperglycaemia related to myotonic dystrophy.
AB  - BACKGROUND: One of the clinical features of myotonic dystrophy is insulin
      resistance with non-obese diabetes mellitus (DM). Recently, the mechanism of
      insulin resistance in patients with myotonic dystrophy was revealed. The optimal
      treatment of DM with myotonic dystrophy has not been established. We report the
      effect of metformin in a patient with myotonic dystrophy without obesity. CASE
      REPORT: A 58-year-old woman (BMI = 22.1 kg/m2) with myotonic dystrophy and DM was
      followed at our clinic. She had been treated with glimepiride for DM for the last
      6 months, without achieving good control (HbA(1c) 9.3%). She was admitted with
      congestive heart failure and cholecystitis. She was treated with diuretics,
      antibiotics and insulin. As her blood glucose fell, we discontinued insulin and
      started glimepiride, but her glycaemic control had worsened. We started metformin
      instead of glimepiride. After 4 weeks of metformin, HbA(1c) was decreased to
      7.4%, while HOMA-IR during glimepiride treatment was 4.9, and 3.7 with metformin.
      Three months later, HbA(1c) was maintained (7.5%). CONCLUSION: It is important to
      choose the optimal treatment for DM in myotonic dystrophy, because the patients
      have hyperinsulinemia caused by specific mechanism and could not reduce the
      insulin resistance. Metformin improved hyperglycemia through increased insulin
      independent glucose uptake in peripheral muscle. We believe metformin is the
      optimal agent for these patients.

PMID- 15717888
TI  - The annual incidence of diabetic complications in a population of patients with
      Type 1 and Type 2 diabetes.
AB  - AIM: The DARTS diabetes register was used to determine incidence rates of
      diabetes and related complications in 1997. METHODS: The diabetes register
      records detailed clinical information for all patients diagnosed with diabetes in
      Tayside, Scotland. The study population included patients who were alive and
      registered with a Tayside GP for the duration of 1997 or who died in Tayside
      during this time. Patients who had diabetes prior to 1997, those who developed
      diabetes in 1997, and those who developed diabetic complications in 1997, were
      identified. RESULTS: In the Tayside population of 385 774 at the start of 1997,
      there were 942 and 6632 patients with Type 1 and Type 2 diabetes, with a further
      29 and 744 patients diagnosed in 1997. The incidence rates (with 95% confidence
      intervals) of diabetic complications per 1000 patients with Type 1 and Type 2
      diabetes, respectively, were: angina 8.8 (4.5-17.3) and 38.4 (33.4-44.2);
      myocardial infarction 8.6 (4.4-16.9) and 21.9 (18.4-25.9); cerebrovascular
      accident 1.1 (0.3-6.0) and 14.2 (11.6-17.5); lower extremity amputation 3.2 (1.2
      9.4) and 3.1 (2.1-4.8); peripheral vascular disease 5.5 (2.4-12.8) and 13.6 (11.0
      16.8); registered blindness 1.1 (0.3-5.9) and 1.6 (0.9-2.9); end-stage renal
      failure 6.4 (3.0-13.8) and 5.0 (3.6-7.0). Mortality was 14.6 per 1000 (9.6-25.7)
      in Type 1 diabetes and 50.0 per 1000 (45.1-55.3) in Type 2 diabetes. CONCLUSION:
      This study provides baseline figures for rates of diabetic complications for Type
      1 and Type 2 diabetes, and confirms the increased burden of macrovascular disease
      in Type 2 diabetes.

PMID- 15717889
TI  - Effect of lower diagnostic thresholds on estimates of prevalence of impaired
      fasting glucose (IFG).

PMID- 15717890
TI  - The potential of motivational interviewing.

PMID- 15717891
TI  - New carotid plaque formation is very common in adult patients with Type 2
      diabetes mellitus.

PMID- 15717892
TI  - Serum levels of L-arginine analogues and glutathione peroxidase and catalase gene
      variants in Type 2 diabetes mellitus patients.

PMID- 15717893
TI  - What can rural agencies do to address the additional costs of rural services? A
      typology of rural service innovation.
AB  - There is a national commitment to ensuring that, regardless of where patients
      live, they should be provided with an acceptable level of service in terms of
      quality, effectiveness and accessibility. Because of differences in the
      distributions of their populations, rural and urban areas present quite different
      challenges for the optimal design of health services and social care. However,
      this has not been fully acknowledged in the development of national policies to
      unify service standards. The problems of providing services in sparsely populated
      areas are not new. However, until the case for a rural premium in English health
      resource allocation is accepted, rural agencies must either tolerate lower levels
      of services (an option made difficult by the introduction of national service
      standards) or develop very different approaches to service delivery. To date,
      there has been little systematic knowledge about the extent of innovative rural
      practice, a paucity of evaluation of such initiatives and few opportunities to
      disseminate learning from one area to another. The present paper begins to
      address this deficit. Drawing upon a review of the formal literature and a
      comprehensive evaluation of projects developed within a rural Health Action Zone,
      it presents a typology of innovative responses at the health/social care
      interface. Examples of service innovations which fall into six broad categories
      are provided. These not only suggest possibilities for the transfer of good
      practice, but also the potential for future research.

PMID- 15717894
TI  - Care needs among the dependent population in Spain: an empirical approach.
AB  - The objective of the present paper was to identify the profile and needs of
      social and healthcare users in Spain who required long-term care. To achieve this
      goal, an extensive empirical study was carried out in 2001 of a typical southern
      European region: the Valencia Autonomous Region in Spain. The method used was a
      questionnaire-based survey. The data collection instrument was a questionnaire
      comprising 119 questions grouped into seven sections: social and demographic
      data; clinical diagnosis and treatment; living environment; degree of dependence
      in activities of daily living (ADLs); cognitive state; social support; and the
      social, demographic and attendance data of the carer, if available. The sampling
      was carried out in two strata, i.e. social and healthcare: first, the authors
      randomly selected the centres and services as sampling points, and then they
      randomly selected the subjects. A total of 1265 people were interviewed. The
      results show different care profiles: users aged under 65 years were mostly
      mentally ill and/or drug users requiring short- and medium-term care from the
      health services, while those aged over 65 years had chronic illnesses for which
      they were actively receiving treatment, were functionally dependent for ADLs, and
      were normally receiving social care that basically provided company and resolved
      functional limitations.

PMID- 15717895
TI  - The Diabetes Continuity of Care Scale: the development and initial evaluation of
      a questionnaire that measures continuity of care from the patient perspective.
AB  - The purpose of the present study was to develop and pilot test a questionnaire to
      assess continuity of care from the perspective of patients with diabetes. Seven
      patient and two healthcare-provider focus groups were conducted. These focus
      groups generated 777 potential items. This number was reduced to 56 items after
      item reduction, face validity testing and readability analysis, and to 47 items
      after a preliminary factor analysis. Readability was assessed as requiring 7-8
      years of schooling. Sixty adult patients with diabetes completed the draft
      Diabetes Continuity of Care Scale (DCCS) at a single point in time to assess the
      validity of the instrument. Patients completed the draft DCCS again 2 weeks later
      to assess test-retest reliability. A provisional factor analysis and grouping
      according to clinical sense yielded five domains: access and getting care, care
      by doctor, care by other healthcare professionals, communication between
      healthcare professionals, and self-care. The internal consistency (Cronbach's
      alpha) for the whole scale was 0.89. The test-retest reliability was r = 0.73.
      The DCCS total score was moderately correlated with some of the measures used to
      establish construct validity. The DCCS could differentiate between patients who
      did and did not achieve specific process and clinical indicators of good diabetes
      care (e.g. Hba1c tested within 6 months). The development of the DCCS was centred
      on the patient's perspective and revealed that the patient perspective regarding
      continuity of care extends beyond the concept of seeing one doctor. Initial
      testing of this instrument demonstrates that it has promise as a reliable and
      valid measure in this area.

PMID- 15717897
TI  - Quality of life among older people in Sweden receiving help from informal and/or
      formal helpers at home or in special accommodation.
AB  - The present study describes and compares quality of life (QoL) and factors which
      predict QoL among people aged 75 years and over who receive help with activities
      of daily living (ADLs) from formal and/or informal helpers. The subjects were
      living at home or in special accommodation in Sweden. A postal questionnaire was
      sent to a randomly selected and age-stratified sample of 8500 people. The
      response rate was 52.8% (n = 4337), and 1247 people [mean age (+/- SD) = 86.4 +/-
      5.9 years] received help and indicated who helped them with ADLs. The findings
      suggest that a greater age, being a woman, being a widow/widower, a higher number
      of health-related complaints, needing more help with ADLs and a lower QoL were
      found among those receiving help in special accommodation in comparison with
      those receiving help at home. The extent of help was highest among those
      receiving help in special accommodation. Having help with ADLs every day at home
      indicated having help from both informal and formal helpers, while respondents
      receiving help from only informal or only formal helpers received the smallest
      amount of help with ADLs. A need for greater help with ADLs, and a higher number
      of self-reported diseases and complaints determined low QoL, whilst a social
      network (contact with more than three people) and a greater age determined high
      QoL. However, who the helpers were did not have a significant influence on QoL;
      it was the extent of help with ADLs that influenced QoL negatively and the
      density of the social network that influenced QoL positively.

PMID- 15717896
TI  - Patients with advanced cancer and family caregivers' knowledge of health and
      community services: a longitudinal study.
AB  - The present study examines the knowledge of health and community services
      reported by patients with advanced cancer and their family caregivers, and
      compares patient-stated use with their knowledge of availability. A longitudinal
      study of the quality of life of patients with advanced cancer was conducted out
      of the cancer services of The Canberra Hospital, a teaching service, in Canberra,
      Australian Capital Territory, Australia. Some 317 subjects were recruited
      sequentially, comprising patients (n = 181) and their nominated family caregivers
      (n = 136). Patients were more aware of the available health and community support
      services compared with their caregivers, and differences were significant for
      most allied professional services, as well as some key supportive care
      institutions and community programmes. Knowledge of community support services
      was variable and low for those specifically associated with terminal care. While
      congruence of knowledge for dyads was quite low in some areas, overall household
      knowledge was high. The identified sources were mainly non-medical. Nurses,
      social workers and alternative practitioners, as well as family, friends and
      commercial sources were the main categories which were identified. No
      statistically significant changes in knowledge or sources of information occurred
      over time. Further longitudinal research would assist healthcare teams to
      understand the role of health and community services in the advanced cancer
      setting. The identification of systemic and regional weaknesses in communication
      may assist in improving family knowledge and improve timely access to important
      supports in the advanced cancer setting.

PMID- 15717898
TI  - 'Making the move': relatives' experiences of the transition to a care home.
AB  - Despite a growing awareness of the significance of helping a relative to relocate
      to a care home as a key phase in the caregiving career, relatively few studies in
      the UK have explored this experience in depth. The research on which the present
      paper is based sought to better understand experiences of nursing home placement
      from the viewpoint of relatives. The study was informed by a constructivist
      perspective. Data were collected in 37 semi-structured interviews involving 48
      people who had assisted a close relative to move into a nursing home. Data
      analysis revealed three phases of the transition from the relatives' perspective:
      'making the best of it'; 'making the move'; and 'making it better'. The
      relatives' experiences across these phases were understood in terms of five
      continua, reflecting the extent to which they felt they were: operating 'under
      pressure' or not; 'working together' or 'working alone'; 'supported' or
      'unsupported', both practically and emotionally; 'in the know' or 'working in the
      dark'; and 'in control of events' or not. This paper reports on the findings
      which relate to the second phase of the transition, 'making the move', which
      relates to experiences around the time of relocation to the care home
      environment. The findings suggest that health and social care practitioners have
      enormous potential to influence relatives' experiences of nursing home entry.
      Experiences are enhanced if family carers perceive that they are able to work in
      partnership with care staff in order to ease the transition for the older person.

PMID- 15717899
TI  - Joint working in community mental health teams: implementation of an integrated
      care pathway.
AB  - Abstract Integration of community mental health services is a key policy
      objective that aims to increase quality and efficiency of care. Integrated care
      pathways (ICPs) are a mechanism designed to formalise multi-agency working at an
      operational level and are currently being applied to mental health services.
      Evidence regarding the impact of this tool to support joint working is mixed, and
      there is limited evidence regarding the suitability of ICPs for complex,
      community-based services. The present study was set in one primary care trust
      (PCT) in Scotland that is currently implementing an ICP for community mental
      health teams (CMHTs) across the region. The aim of the study was to investigate
      professionals' experiences and views on the implementation of an ICP within adult
      CMHTs in order to generate learning points for other organisations which are
      considering developing and implementing such systems. The study used qualitative
      methods which comprised of individual interviews with three CMHT leaders and two
      service development managers, as well as group interviews with members of four
      adult CMHTs. Data was analysed using the constant comparison method. Participants
      reported positive views regarding joint working and the role of an ICP in theory.
      However, in practice, teams were not implementing the ICP. Lack of integration at
      higher organisational levels was found to create conflicts within the teams which
      became explicit in response to the ICP. Implementation was also hindered by lack
      of resources for ongoing support, team development and change management. In
      conclusion, the study suggests that operational systems such as ICPs do not
      address and cannot overcome wider organisational barriers to integration of
      mental health services. Integrated care pathways need to be developed with
      strategic input as well as practitioner involvement and ownership. Team
      development, education about integration and change management are essential if
      ICPs are to foster and support joint working in integrated teams.

PMID- 15717901
TI  - 'Implementation deficit' and 'street-level bureaucracy': policy, practice and
      change in the development of community nursing issues.
AB  - The present paper examines the mechanisms by which health and social care
      policies put forward by the Government may be translated into community nursing
      practice. Data from a research project on community nurse case managers were re
      examined in the light of two classic theories often cited by policy analysts
      (i.e. implementation theory and 'street-level bureaucracy'). It was found that
      the extent to which nurses adopted the case management role, and the model of
      choice, depended on four major interrelated variables, namely: (1) the clarity of
      policy guidance; (2) the extent to which it coincided with professional (nursing)
      values; (3) local practices and policies; and (4) the personal vision of the
      community nurse. It is argued that this framework may have wider relevance, and
      this was tested out in two ways. First, major change in one of these variables
      (Government policy) over time was analysed for its effect on case management
      practice via the remaining variables. Secondly, an unrelated, but policy
      initiated, nursing issue (nurse prescribing) was briefly examined in the light of
      the framework. It is suggested that this framework may be of some use when
      considering the likely practice response to policy-related changes in community
      nursing.

PMID- 15717902
TI  - Determinants in the development of advanced nursing practice: a case study of
      primary-care settings in Hong Kong.
AB  - Different factors have been shown to influence the development of models of
      advanced nursing practice (ANP) in primary-care settings. Although ANP is being
      developed in hospitals in Hong Kong, China, it remains undeveloped in primary
      care and little is known about the factors determining the development of such a
      model. The aims of the present study were to investigate the contribution of
      different models of nursing practice to the care provided in primary-care
      settings in Hong Kong, and to examine the determinants influencing the
      development of a model of ANP in such settings. A multiple case study design was
      selected using both qualitative and quantitative methods of data collection.
      Sampling methods reflected the population groups and stage of the case study.
      Sampling included a total population of 41 nurses from whom a secondary volunteer
      sample was drawn for face-to-face interviews. In each case study, a convenience
      sample of 70 patients were recruited, from whom 10 were selected purposively for
      a semi-structured telephone interview. An opportunistic sample of healthcare
      professionals was also selected. The within-case and cross-case analysis
      demonstrated four major determinants influencing the development of ANP: (1)
      current models of nursing practice; (2) the use of skills mix; (3) the perceived
      contribution of ANP to patient care; and (4) patients' expectations of care. The
      level of autonomy of individual nurses was considered particularly important.
      These determinants were used to develop a model of ANP for a primary-care
      setting. In conclusion, although the findings highlight the complexity
      determining the development and implementation of ANP in primary care, the
      proposed model suggests that definitions of advanced practice are appropriate to
      a range of practice models and cultural settings. However, the findings highlight
      the importance of assessing the effectiveness of such models in terms of cost and
      long-term patient outcomes.

PMID- 15717903
TI  - Health risk appraisal for older people in general practice using an expert
      system: a pilot study.
AB  - The prevention of disability in later life is a major challenge facing
      industrialised societies. Primary care practitioners are well positioned to
      maintain and promote health in older people, but the British experience of
      population-wide preventive interventions has been disappointing. Health risk
      appraisal (HRA), an emergent information-technology-based approach from the USA,
      has the potential for fulfilling some of the objectives of the National Service
      Framework for Older People. Information technology and expert systems allow the
      perspectives of older people on their health and health risk behaviours to be
      collated, analysed and converted into tailored health promotion advice without
      adding to the workload of primary care practitioners. The present paper describes
      a preliminary study of the portability of HRA to British settings. Cultural
      adaptation and feasibility testing of a comprehensive health risk assessment
      questionnaire was carried out in a single group practice with 12,500 patients, in
      which 58% of the registered population aged 65 years and over participated in the
      study. Eight out of 10 respondents at all ages found the questionnaire easy or
      very easy to understand and complete, although more than one-third had or would
      have liked assistance. More than half felt that the length of the questionnaire
      was about right, and one respondent in 10 disliked some questions. Of those who
      completed the questionnaire and received tailored, written health promotion
      advice, 39% provided feedback on this with comments that can be used for
      increasing the acceptability of tailored advice. These findings have informed a
      wider exploratory study in general practice.

PMID- 15717904
TI  - Quality of life from the viewpoint of patients with dementia in Japan: nurturing
      through an acceptance of dementia by patients, their families and care
      professionals.
AB  - The quality of life (QoL) of patients with dementia was investigated from the
      patient's viewpoint, and the role of an acceptance of dementia in maintaining
      important and distinctive elements of QoL was analysed by questionnaire and
      interview methods. The subjects of the present study were 18 patients, 21 family
      members and eight members of staff at a day-care facility in Japan. Patients with
      dementia hoped to maintain an 'ordinary' way of life. Living peacefully, living
      together, living healthily and helping each other were considered by patients
      with dementia to be the important elements of their QoL. Living happily in the
      present is important, but hopes and expectations for the maintenance of human
      values in their future lives are of greater importance in their estimation of
      QoL. Through recognizing these needs, a culture and understanding of 'living with
      dementia' can be nurtured. A dynamic process involving the mutual acceptance of
      dementia in the relationships between patients with dementia, their families and
      care professionals enabled elderly people to surmount their initial troubles, and
      to recoup and activate their former humane attitudes. Positive thinking
      reappeared and new forms of relationships emerged. The patients, their families
      and the care professionals came to understand each other better and gained the
      sense of 'living together'. The process began with 'confronting' the situation
      and progressed to the final stage of 'acceptance': the patient with dementia was
      confronted with the dementia itself, the family was confronted with the elderly
      person as a human being, and the care professional was confronted with her or
      himself. At first, the care professionals had felt a sense of social
      responsibility for delivering justice, but they had gradually noticed that they
      were themselves relieved of the strain resulting from these attitudes. Acceptance
      of dementia by the care professional was important in carrying forward this
      dynamic process, which helps to ensure the desired QoL for the patient with
      dementia.

PMID- 15717905
TI  - Social support in the healthcare setting: the role of volunteers.
AB  - The participation of volunteers in the National Health Service (NHS) has been
      actively promoted during recent years, particularly within community and primary
      healthcare services (National Health Service 1996, 1998). As a consequence,
      volunteers currently make a significant contribution to health and social care
      within the UK. Concerning this contribution, the literature often portrays the
      volunteers' role as one of providing social support. In the present paper, the
      authors attempt to explore this role in more detail, drawing on interview data
      from studies of two separate volunteer programmes. One of these considered the
      role of volunteers supporting older hospitalised patients (Davies et al. 2001),
      and the other was based within general practice (Faulkner 2003, 2004). The social
      support provided by these programmes is considered from the perspective of four
      broad support mechanisms described by Langford et al. (1997), namely: emotional
      support; informational support; appraisal support; and instrumental support.
      Secondary analysis examines the potential contribution of volunteers to patient
      well-being.

PMID- 15717906
TI  - A qualitative study exploring the experiences and views of mothers, health
      visitors and family support centre workers on the challenges and difficulties of
      parenting.
AB  - Successive policy documents have referred to the need to support parents as an
      approach to reducing social exclusion, behaviour problems among young people and
      crime rates. Much of the rhetoric focuses on professional intervention, and there
      is less attention paid to the views and experiences of parents themselves. The
      present study explores the experiences and views of mothers, health visitors and
      family support centre workers who work with parents on the challenges and
      difficulties of parenting children under the age of 6 years. It provides an
      appreciation of their views on effective parenting and how parents can be helped
      to feel more effective in the parenting role. Focus groups, which were
      exploratory and interactive in form, were conducted across three primary care
      trusts in Hertfordshire, UK. Three samples were purposively selected in order to
      examine the range and diversity of experiences and views about parenting, and
      included the parents of children up to the age of 6 years, health visitors and
      family support centre workers. The mothers were those waiting to attend a
      parenting programme, and included first-time mothers and those with more than one
      child. The health visitors and family support workers had a range of experience
      in working with parents and children, and included those who were facilitating
      parenting programmes and those who were not. A number of themes emerged
      surrounding the challenges and difficulties of parenting and effective parenting,
      including expectations of others, establishing routines, play, behavioural issues
      and discipline, empathy, and communication. Similar themes emerged from all
      groups; however, there were qualitative differences between parents and
      professionals in the way in which these issues were expressed. Key statements
      from the parent focus groups have been developed into self-efficacy statements,
      which will be used as input to the development of a tool to measure the
      effectiveness of parenting programmes.

PMID- 15717907
TI  - Fixing the system? The experience of service users of the quasi-market in
      disability services in Australia.
AB  - A qualitative study involving semi-structured interviews with 31 people with
      disabilities and 32 carers in the state of Queensland, Australia, found that
      their experience of supportive service delivery had not improved despite reforms
      of the service delivery system driven by a version of the quasi-market model.
      Instead of delivering increased consumer choice and improved efficiency in
      service delivery, service users experienced inadequate service supply, service
      cutbacks, and an increased emphasis on cost subsidisation and assessment
      processes. Additionally, few consumers felt that individualised funding
      arrangements had personally delivered the benefits which the quasi-market model
      and associated policy paradigm had indicated that they should receive. For many
      consumers, the notion of consumer 'choice' around service provision was
      fictitious and they felt that any efficiency gains were at the agency level,
      largely at the consumers' cost. It is concluded that there appears to be no
      particular benefit to service users of quasi-market reforms, particularly in
      policy contexts where service delivery systems are historically under-funded.

PMID- 15717908
TI  - Living with motor neurone disease: lives, experiences of services and suggestions
      for change.
AB  - Palliative care involves the complete, holistic care of people with progressive
      illness and their families. People living with motor neurone disease (MND)
      require a range of multidisciplinary palliative care services. However, there are
      significant gaps in our understanding of these people's lives, experiences of
      services and their suggestions for service change. The present study addressed
      the following questions: (1) What are the lived experiences of people living with
      MND? (2) What are people's experiences of services? and (3) Can improvements to
      care be identified? A qualitative research design was adopted using semi
      structured interviews. The topic guide was developed from existing literature.
      The study was based in three boroughs in London, UK. People living with MND and
      professionals were drawn from a database at King's College Hospital, and
      additionally, through 'snowball' sampling. Nine people with MND, five
      carers/family members and 15 professionals took part in the interviews. These
      interviews were audio-taped, transcribed and checked for accuracy against the
      original recordings. Themes within the interviews were coded and grouped. The
      analysis was facilitated with the NVIVO computer software package. The findings
      are presented within three substantive groups: (1) the impact of MND on people's
      lives (the physical impacts of the illness, including increasing disability;
      social issues, including restrictions on social activities; and adjustments to
      people's lives, including methods of coping with the illness); (2) experiences of
      services (accessing service entitlements, information sources, professionals'
      attitudes and approaches, and professionals' knowledge and understanding of MND);
      and (3) suggestions for service change (better information and communication,
      including information on service entitlements; improved knowledge amongst
      professionals about MND; and some suggestions for service restructuring). This
      study brings a fresh approach to understanding the impacts of MND and the ways in
      which services can be improved to meet people's needs. The paper concludes with
      methodological considerations, the implications of the findings for practitioners
      and policy makers, and suggestions for further research.

PMID- 15717909
TI  - Exploring risk perception and behaviour of homeless injecting drug users
      diagnosed with hepatitis C.
AB  - Injecting drug users (IDUs) are at the greatest risk of hepatitis C infection by
      using any item of injecting equipment that has come into contact with
      contaminated blood. Alongside this, homeless IDUs have been identified as being
      at increased risk of harm in their illicit drug taking behaviour. This study
      interviewed 17 hepatitis C positive homeless IDUs about their injecting
      practices. In-depth interviews explored the impact of a positive hepatitis C
      diagnosis on their injecting and identified their risk behaviours and
      perceptions. The interviews were tape-recorded, transcribed and analysed using
      the framework approach. Homeless IDUs engaged in both high risk and unhygienic
      injecting practices, such as using drugs outside and in public places, sharing
      injecting equipment and re-using cleaned needles. Excessive needle reuse whilst
      in prison was also identified. However, the findings were not universally bleak
      as a positive diagnosis of hepatitis C did lead to some behaviour change towards
      safer injecting and some adopted other lifestyle and behaviour changes. It was,
      however, common for homeless people to devolve responsibility for preventing
      hepatitis C transmission to their peers, especially when injecting with others.
      Knowledge regarding possible transmission through injecting paraphernalia
      appeared to make users more careful to reduce it through these routes. Placing a
      continuous emphasis on health promotion is therefore important in educating IDUs
      about the hepatitis C transmission risks associated with injecting drug use.
      Information regarding safer and hygienic use, including accurate information
      regarding the most effective methods to clean used equipment, must be re-enforced
      by people working with homeless injecting drug users.

PMID- 15717911
TI  - Enabling frail older people with a communication difficulty to express their
      views: the use of Talking Mats as an interview tool.
AB  - The aim of the present study was to obtain the views of frail older people with
      communication impairments using an innovative interviewing method, Talking Mats.
      People with a communication disability are often omitted from qualitative
      research studies since they cannot respond to the more traditional methods of
      interviewing. However, their views are important and they may, in fact, have
      additional insights because of their communication situation. The 10 participants
      in this study were frail older people with a range of communication difficulties
      with causes including stroke, dementia and hearing loss. They had all recently
      (within 6 months) moved into care homes. Each participant was interviewed using
      Talking Mats to obtain their views on four aspects of their life: activities,
      people, environment and self. The findings are presented in a visual way, and the
      four life themes are discussed with reference to the different participants. Many
      insights were gained, such as the participants' views of the activities which
      they like and dislike, and the views of some of the people in the study about
      their nursing home environment. The advantages of the Talking Mats as an
      interview method for research, practice and policy in the care of frail older
      people are described. The study concludes that Talking Mats is a useful and
      enjoyable method of allowing frail older people with a communication disability
      to express views which they have difficulty conveying otherwise.

PMID- 15717912
TI  - A comparison of GPs and nurses in their approach to psychological disturbance in
      primary care consultations.
AB  - It has frequently been reported that GPs fail to diagnose many of the
      psychological problems that present to them. It also appears that practice nurses
      working in primary care also show similar diagnostic 'failings'. This study
      extends these observations by reporting the psychiatric diagnostic practices of
      GPs and nurses working in the same settings of six general practices. After each
      consultation the health professional involved assessed the degree of
      psychological morbidity and the amount of time they had spent attending to this
      problem. The health professionals' assessment was compared with the score from a
      General Health Questionnaire completed by the patient. Analysis of 1646
      consultations revealed that GPs saw patients with more psychological problems
      than nurses. Nurses, however, spent significantly more time dealing with their
      psychological workload than their GP colleagues, after allowing for the fact that
      they saw fewer patients in this category. This observation raises the question of
      whether this use of scarce time resource in the consultation is appropriate.

PMID- 15717913
TI  - Knowing the diagnosis and counselling the relatives of a person with dementia:
      the perspective of home nurses and home care workers in Belgium.
AB  - Home nurses and home care workers share the care for a person with dementia with
      family caregivers, and are confronted with their needs for medical and service
      related information, for advice on how to cope with the behaviour changes, and
      for emotional support. The first objective of the present study was to describe
      some of the conditions for effective counselling, such as the perception that
      knowing the diagnosis has positive consequences for the formal caregivers. A
      second objective was to describe the formal caregivers' counselling practice, and
      ascertain its relationship with the psychological variables of attitudes, self
      efficacy and subjective norm. A postal questionnaire was sent to 287 home nurses
      and 1259 home care workers in a defined region of Belgium; the questionnaire was
      returned by 169 home nurses (58.9% response) and 665 home care workers (52.8%
      response). The Theory of Planned Behaviour was the organising framework which
      underpinned the development of the instruments. Only the 168 home nurses and 601
      home care workers reporting experience with caregiving to people with dementia
      were included in the analysis. Formal caregivers indicated that knowing the
      diagnosis was important, but it could facilitate or hinder caregiving. They were
      able to describe behavioural characteristics which are indicative of dementia,
      but only in a limited way, and their strategies to uncover the diagnosis were
      also limited. Formal caregivers reported that they supported family members
      emotionally, advised about communication with the person with dementia and
      informed family caregivers about services. However, providing family caregivers
      with information about dementia lagged behind these forms of support. In general,
      nurses scored higher than home care workers. Multiple linear regression analysis
      was used to investigate the relationships between self-reported practice and the
      concepts of the model. In both professions, attitudes and self-efficacy were
      found to be strong independent predictors, and the implications for practice are
      discussed.

PMID- 15717914
TI  - 'Working at the margins' or 'leading from behind'? A Canadian study of hospital
      community collaboration.
AB  - Collaboration between hospitals and community organisations has been promoted
      over the past 20 years by various levels of government, hospital associations,
      health promotion advocates, and others at the state/province, national and
      international levels as a way to improve the 'efficiency of the system', reduce
      duplication, enhance effectiveness and service coordination, improve continuity
      of care, and enhance community capacity to address complex issues. Nevertheless,
      and despite a growing literature on interagency collaboration, systematic
      documentation and empirical analysis of hospital-community collaboration (HCC) is
      almost completely lacking in the literature, particularly as regards
      collaborations that address the determinants of health beyond the hospital walls.
      In this paper, we describe the methodology and key findings from a research study
      of HCC. The Hospital Involvement in Community Action (HICA) study undertook
      detailed qualitative case studies (in four urban, suburban, rural and northern
      locations) and a telephone survey (of 139 community organisations in a large
      urban centre) in order to learn about the range of collaborations and working
      relationships that exist between hospitals and community agencies in the province
      of Ontario (Canada), and the factors that influenced (enabled and/or hindered)
      HCC. Particular attention was paid to barriers and enablers at three nested
      levels of context (policy, hospital and community) and, drawing primarily on the
      qualitative case studies, it is this aspect that is the focus of this paper. That
      such collaborations continue to be widespread despite a generally unfavourable
      policy environment and hospital institutional culture that poses significant
      barriers, suggests that the extent to which HCC flourishes (or exists at all)
      crucially depends on the presence and ongoing enthusiasm/commitment of one or
      more 'champions' within the hospital, and the commitment of both parties to
      overcome the marked cultural differences between hospital and community. We
      conclude with a discussion of implications for policy and practice.

PMID- 15717915
TI  - The feasibility and acceptability of a specialist health and social care team for
      the promotion of health and independence in 'at risk' older adults.
AB  - Population ageing, escalating costs in pensions, health-care and long-term care
      have prompted a new policy agenda for active ageing and quality of life in old
      age across the European Union and other developed countries. In England, the
      National Service Framework for Older People (NSF OP) explicitly demands for the
      first time that the NHS and local authorities, in partnership, agree programmes
      to promote health ageing and to prevent disease in older people. These programmes
      are expected to improve access for older people to mainstream health promotion
      services and also to develop multiagency initiatives to promote health,
      independence and well-being in old age. This paper describes the evaluation of
      one interagency project team established to test out mechanisms for addressing
      health promotion for older people through primary care. A mixed methodology was
      used to understand the processes of service development, the impact of the team's
      intervention, and the primary and secondary outcomes for older people. The
      project demonstrated that multi-agency partnerships have the potential to improve
      the quality of the lives of older people deemed 'at risk' by their general
      practitioners, particularly through income generation but also in the
      identification of medical problems such as unrecognised hypertension, hearing
      loss and visual loss. It also offered some key learning points for other multi
      agency groups developing similar services.

PMID- 15717916
TI  - The impact of 'statutory duties' on mental health social workers in the UK.
AB  - In the UK, applications for involuntary admission to psychiatric units are made
      mainly by specially trained approved social workers (ASWs). Proposed changes in
      the legislation will permit other professionals to undertake these statutory
      duties. This study aimed to examine how ASW status impacts upon work pattern and
      workload stresses by comparing ASWs with other mental health social workers who
      did not carry statutory responsibilities. A multimethod design was adopted that
      included a cross-sectional national survey of mental health social workers
      (n=237, including 162 ASWs), and a telephone survey of mental health service
      managers (n=60). Data were collected using a semistructured questionnaire and
      diary, the content of which was derived from focus-group work and standard
      measures. Features of job content, working patterns and conditions were described
      and their association with stress, burnout and job satisfaction examined. ASWs
      were older and had been qualified longer than non-ASWs. The working patterns and
      conditions of the two groups did not differ, although ASWs did more hours on
      duty. ASWs received less support at work, particularly from supervisors and their
      role afforded less decision latitude than that of non-ASWs. ASW status was
      related to an elevated GHQ score, particularly among males. Emotional exhaustion
      was very high (over two-thirds in both groups) but ASWs and non-ASWs did not
      differ in this or any other feature of burnout, only 8% of the sample were
      actually 'burnt-out', being more common among ASWs. ASWs were more dissatisfied
      and were more likely than non-ASWs to want to leave their job. Given that ASW
      status increased stress and job dissatisfaction, especially for men, and was
      related to a desire to leave one's current job, it seems likely that extending
      statutory duties to other professionals will increase levels of stress, burnout
      and dissatisfaction in these groups also. In turn, this might have consequences
      for staff recruitment and retention.

PMID- 15717917
TI  - Multi-agency working in services for disabled children: what impact does it have
      on professionals?
AB  - Whilst agencies in many sectors have been encouraged to work together to better
      meet the needs of service users, multi-agency working is now a central feature of
      government policy. In relation to children's services, the National Service
      Framework, the English green paper, 'Every Child Matters' (DfES, 2003) and the
      Children Bill (DfES 2004) give a high priority to an integrated approach to
      service provision. This paper focuses on multi-agency working for disabled
      children with complex health-care needs, a group of children who, perhaps even
      more than most, require the many professionals who support them and their
      families, to work more closely together. Drawing on the findings from a 3-year
      qualitative research study, this paper examines the impact of working in a multi
      agency service on professionals. Interviews with 115 professionals concluded that
      staff were overwhelmingly positive about working as part of a multi-agency
      service. They reported improvements to their working lives in areas such as
      professional development, communication, collaboration with colleagues, and
      relationships with families with disabled children. However, whilst professionals
      felt that they were able to offer families a more efficient service, there was
      concern that the overall impact of multi-agency working on disabled children and
      their families would be limited.

PMID- 15717918
TI  - Who are your public? A survey comparing the views of a population-based sample
      with those of a community-based public forum in Scotland.
AB  - This paper describes a questionnaire survey, carried out in the NHS Grampian area
      of NE Scotland. It compares responses from 84 members of a community-based public
      forum (39 of whom were sent questionnaires) and a random sample of 10,000 adults
      registered with general practices in Grampian (2,449 of whom were sent
      questionnaires). MAIN OUTCOME MEASURES: differences in demographic profiles and
      opinions about different feedback mechanisms (patient representative, telephone
      helpline and NHS feedback website) and their likely effectiveness in three
      different scenarios. 46% of community forum members consented to take part
      compared to 24% of the population sample. Younger people and residents in more
      deprived areas were under-represented in both groups. Community forum members
      were older (only one under 40 years of age), more likely to be retired and not in
      employment. Internet access was similar in both groups. Opinions about different
      systems of feeding back views to the NHS varied but community forum members were
      more likely to be positive in their opinions about the value of different
      feedback mechanisms and less likely to think they were 'a waste of NHS money'.
      Responses to three scenarios revealed similar opinions, but on some issues, there
      were key differences in the responses from the two groups. Community forum
      members were more likely to consider writing a letter as a means of getting
      something done about a problem and were more likely to talk to their GP if
      experiencing a problem than respondents in the main group. In general their
      responses were more positive towards the NHS. There is a need to ensure a broad
      basis for membership of public forums and/or proactively seek the views of groups
      that are under-represented if public forums are to be used to represent the views
      of the wider population and inform decision making in the NHS.

PMID- 15717919
TI  - How place matters: unpacking technology and power in health and social care.
AB  - The devolution of care into nontraditional community-based settings has led to a
      proliferation of sites for health and social care. Despite recent
      (re)formulations of 'evidence-based' approaches that stress the importance of
      optimizing interventions to best practice by taking into account the uniqueness
      of place, there is relatively little guidance in the literature and few attempts
      to systematically 'unpack' key dimensions of settings most relevant to policy,
      practice and research. In this paper, we explore how place matters for health and
      social care. In effect, we propose making place the lens through which to view
      practice, and not simply an interesting sideline focus. We focus specifically on
      (a) the emplacement of power relations in health and social care in and across
      settings; and (b) the pervasive (and often unrecognised) influence of technology
      on and in place (both 'mundane' and more visible 'high' technologies) as arguably
      among the most significant and pervasive (and often overlooked) dimensions of
      place pertinent to health and social care in both traditional (institutional) and
      nontraditional (community) settings. Drawing on diverse disciplinary literatures,
      we seek to make visible certain issues and bodies of work that health
      professionals may not be aware of, and which often remain inaccessible to
      practitioners and applied researchers on account of their density, complexity,
      and specialised terminology. In particular, drawing on the rich tradition of
      cultural studies, we advance the culture of place as a rubric for understanding
      the complex interrelationship between power, technology, culture, and place.
      Several fruitful avenues for place-sensitive research of health and social care
      practice (and its effects) are suggested.

PMID- 15717921
TI  - The pre-vaccination regional epidemiological landscape of measles in Italy:
      contact patterns, effort needed for eradication, and comparison with other
      regions of Europe.
AB  - BACKGROUND: Strong regional heterogeneity and generally sub-optimal rates of
      measles vaccination in Italy have, to date, hampered attainment of WHO targets
      for measles elimination, and have generated the need for the new Italian National
      Measles Elimination Plan. Crucial to success of the plan is the identification of
      intervention priorities based upon a clear picture of the regional epidemiology
      of measles derived from the use of data to estimate basic parameters. Previous
      estimates of measles force of infection for Italy have appeared anomalously low.
      It has been argued elsewhere that this results from Italian selective under
      reporting by age of cases and that the true measles force of infection in Italy
      is probably similar to that of other European countries. A deeper examination of
      the evidence for this conjecture is undertaken in the present paper. METHODS:
      Using monthly regional case notifications data from 1949 to the start of
      vaccination in 1976 and notifications by age from 1971-76, summary equilibrium
      parameters (force of infection (FOI), basic reproductive ratio (R0) and critical
      vaccination coverage (pc)) are calculated for each region and for each of 5
      plausible contact patterns. An analysis of the spectra of incidence profiles is
      also carried out. Finally a transmission dynamics model is employed to explore
      the correspondence between projections using different estimates of force of
      infection and data on seroprevalence in Italy. RESULTS: FOI estimates are lower
      than comparable European FOIs and there is substantial regional heterogeneity in
      basic reproductive ratios; certain patterns of contact matrices are demonstrated
      to be unfeasible. Most regions show evidence of 3-year epidemic cycles or longer,
      and compared with England & Wales there appears to be little synchronisation
      between regions. Modelling results suggest that the lower FOI estimated from
      corrected aggregate national data matches serological data more closely than that
      estimated from typical European data. CONCLUSION: Results suggest forces of
      infection in Italy, though everywhere remaining below the typical European level,
      are historically higher in the South where currently vaccination coverage is
      lowest. There appears to be little evidence to support the suggestion that a
      higher true force of infection is masked by age bias in reporting.

PMID- 15717922
TI  - Bilateral recurrent discloation of the patella associated with below knee
      amputation: a case report.
AB  - BACKGROUND: Recurrent dislocation of the patella in patients with below knee
      amputation is a known entity. Abnormally high-riding patella (patella alta) and
      medial patellofemoral ligament insufficiency in these patients predisposes them
      to patellar instability. The established treatment of this problem is surgical
      realignment. CASE PRESENTATION: A 25 year old male patient with bilateral below
      knee amputation presented with bilateral recurrent dislocation of the patella
      while walking on knees on uneven ground. Clinical and radiographic studies showed
      patella alta. A simple shoe modification was used to treat this patient.
      CONCLUSIONS: A simple shoe modification can be used to treat such a condition
      which is otherwise treated surgically.

PMID- 15717923
TI  - The uses of provincial administrative health databases for research on palliative
      care: Insights from British Columbia, Canada.
AB  - BACKGROUND: Research indicating that people increasingly prefer to die at home
      suggests that palliative care is likely to play a more prominent role in the
      future of Canada's health care system. Unfortunately, at a time when research
      evidence should be informing policy and service delivery, little is known about
      health service utilization by Canadians at the end of life. One existing
      mechanism that can help address this gap is provincial administrative health
      data. The purpose of this study was to explore the potential of administrative
      health data to identify characteristics of palliative care users, patterns of
      formal service utilization and predictors of palliative care use. METHODS:
      Bivariate and multivariate analyses were used to examine data from the Capital
      Health Region, British Columbia Linked Health Databases for the period 1992/93 to
      1998/99. The databases examined include continuing care, physician claims,
      hospital separations, and vital statistics. As the name implies, these databases
      can be linked at the individual level using unique identifiers so that health
      services utilization can be tracked across sectors. RESULTS: General patterns of
      service use among palliative care patients suggest that general practitioner and
      medical specialist visits have decreased over time and the utilization of
      hospital beds has increased. Utilization of community-based services (i.e. home
      support and home nursing care) shows an overall pattern of decline. However, when
      compared to non-palliative care patients, palliative care patients spent fewer
      nights in hospital, used fewer hours of home support, and had a greater number of
      home nursing care visits. CONCLUSIONS: Administrative health databases can
      provide valuable information for examining service utilization patterns over
      time. However, given that decisions surrounding the designation of palliative
      care include factors beyond the scope of administrative databases (such as
      quality of life, personal preferences, social support), these databases should
      only be seen as one source of information to inform service delivery and policy
      decision making.

PMID- 15717924
TI  - Novel hepatocyte growth factor (HGF) binding domains on fibronectin and
      vitronectin coordinate a distinct and amplified Met-integrin induced signalling
      pathway in endothelial cells.
AB  - BACKGROUND: The growth of new blood vessels in adult life requires the initiation
      of endothelial cell migration and proliferation from pre-existing vessels in
      addition to the recruitment and differentiation of circulating endothelial
      progenitor cells. Signals emanating from growth factors and the extracellular
      matrix are important in regulating these processes. RESULTS: Here we report that
      fibronectin (FN) and vitronectin (VN) modulate the responses of endothelial cells
      to HGF (Scatter Factor), an important pro-angiogenic mediator. Novel binding
      sites for HGF were identified on both FN and VN that generate molecular complexes
      with enhanced biological activity and these were identified in the supernatants
      of degranulated platelet suspensions implicating their release and formation in
      vivo. In the absence of co-stimulation with an ECM glycoprotein, HGF could not
      promote endothelial cell migration but retained the capacity to induce a
      proliferative response utilising the Map kinase pathway. Through promoting Met
      Integrin association, HGF-FN and HGF-VN complexes coordinated and enhanced
      endothelial cell migration through activation of the PI-3 kinase pathway
      involving a Ras-dependent mechanism whereas a Ras-independent and attenuated
      migratory response was promoted by co-stimulation of cells with HGF and a non
      binding partner ECM glycoprotein such as collagen-1. CONCLUSIONS: These studies
      identify a novel mechanism and pathway of HGF signalling in endothelial cells
      involving cooperation between Met and integrins in a Ras dependent manner. These
      findings have implications for the regulation of neovascularization in both
      health and disease.

PMID- 15717925
TI  - FlyPNS, a database of the Drosophila embryonic and larval peripheral nervous
      system.
AB  - BACKGROUND: The embryonic and larval peripheral nervous system of Drosophila
      melanogaster is extensively studied as a very powerful model of developmental
      biology. One main advantage of this system is the ability to study the origin and
      development of individual sensory cells. However, there remain several
      discrepancies regarding the organization of sensory organs in each abdominal
      segment A1-A7. DESCRIPTION: We have constructed a web site called FlyPNS (for Fly
      Peripheral Nervous System) that consolidates a wide range of published and
      unpublished information about the embryonic and larval sensory organs. It
      communicates (1) a PNS pattern that solves the discrepancies that have been found
      in the recent literature, (2) the correspondence between the different
      nomenclatures that have been used so far, (3) a comprehensive description of each
      sensory organ, and (4) a list of both published and unpublished markers to
      reliably identify each PNS cell. CONCLUSIONS: The FlyPNS database integrates
      disparate data and nomenclature and thus helps understanding the conflicting
      observations that have been published recently. Furthermore, it is designed to
      provide assistance in the identification and study of individual sensory cells.
      We think it will be a useful resource for any researcher with interest in
      Drosophila sensory organs.

PMID- 15717926
TI  - Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and
      mammary tumorigenesis.
AB  - BACKGROUND: The human psoriasin (S100A7) gene has been implicated in inflammation
      and tumor progression. Implementation of a mouse model would facilitate further
      investigation of its function, however little is known of the murine psoriasin
      gene. In this study we have cloned the cDNA and characterized the expression of
      the potential murine ortholog of human S100A7/psoriasin in skin inflammation and
      mammary tumorigenesis. METHODS: On the basis of chromosomal location,
      phylogenetic analysis, amino acid sequence similarity, conservation of a putative
      Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin
      gene expression (measured by RT-PCR and in-situ hybridization) with those of
      human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine
      ortholog of human psoriasin/S100A7. RESULTS: Although mouse S100A7/psoriasin is
      poorly conserved relative to other S100 family members, its pattern of expression
      parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was
      significantly upregulated in relation to inflammation. In murine mammary gland
      expression is also upregulated in mammary tumors, where it is localized to areas
      of squamous differentiation. This mirrors the context of expression in human
      tumor types where both squamous and glandular differentiation occur, including
      cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a
      putative Jab1 binding motif that mediates many downstream functions of the human
      S100A7 gene. CONCLUSION: These observations and results support the hypothesis
      that the mouse S100A7 gene is structurally and functionally similar to human
      S100A7 and may offer a relevant model system for studying its normal biological
      function and putative role in tumor progression.

PMID- 15717927
TI  - The domain architecture of large guanine nucleotide exchange factors for the
      small GTP-binding protein Arf.
AB  - BACKGROUND: Small G proteins, which are essential regulators of multiple cellular
      functions, are activated by guanine nucleotide exchange factors (GEFs) that
      stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic
      domain responsible for nucleotide exchange is in general associated with non
      catalytic domains that define the spatio-temporal conditions of activation. In
      the case of small G proteins of the Arf subfamily, which are major regulators of
      membrane trafficking, GEFs form a heterogeneous family whose only common
      characteristic is the well-characterized Sec7 catalytic domain. In contrast, the
      function of non-catalytic domains and how they regulate/cooperate with the
      catalytic domain is essentially unknown. RESULTS: Based on Sec7-containing
      sequences from fully-annotated eukaryotic genomes, including our annotation of
      these sequences from Paramecium, we have investigated the domain architecture of
      large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi
      traffic. Multiple sequence alignments combined with the analysis of predicted
      secondary structures, non-structured regions and splicing patterns, identifies
      five novel non-catalytic structural domains which are common to both subfamilies,
      revealing that they share a conserved modular organization. We also report a
      novel ArfGEF subfamily with a domain organization so far unique to alveolates,
      which we name TBS (TBC-Sec7). CONCLUSION: Our analysis unifies the BIG and GBF
      subfamilies into a higher order subfamily, which, together with their being the
      only subfamilies common to all eukaryotes, suggests that they descend from a
      common ancestor from which species-specific ArfGEFs have subsequently evolved.
      Our identification of a conserved modular architecture provides a background for
      future functional investigation of non-catalytic domains.

PMID- 15717928
TI  - Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial
      PNET is not caused by JC virus.
AB  - BACKGROUND: p53 mutations are relatively uncommon in medulloblastoma, but
      abnormalities in this cell cycle pathway have been associated with anaplasia and
      worse clinical outcomes. We correlated p53 protein expression with pathological
      subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC
      virus, which results in p53 protein accumulation, was also examined. METHODS: p53
      protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3
      atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive
      neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences
      were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples
      using quantitative polymerase chain reaction. RESULTS: p53 expression was
      detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic
      medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53
      immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically
      significant. Log rank analysis of clinical outcome revealed significantly shorter
      survival in patients with p53 immunopositive embryonal tumors. No JC virus was
      identified in the embryonal brain tumor samples, while an endogenous human
      retrovirus (ERV-3) was readily detected. CONCLUSION: Immunoreactivity for p53
      protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non
      anaplastic tumors, and is associated with worse clinical outcomes. However, JC
      virus infection is not responsible for increased levels of p53 protein.

PMID- 15717929
TI  - FADD adaptor in cancer.
AB  - FADD (Fas Associated protein with Death Domain) is a key adaptor molecule
      transmitting the death signal mediated by death receptors. In addition, this
      multiple functional protein is implicated in survival/proliferation and cell
      cycle progression. FADD functions are regulated via cellular sublocalization,
      protein phosphorylation, and inhibitory molecules. In the present review, we
      focus on the role of the FADD adaptor in cancer. Increasing evidence shows that
      defects in FADD protein expression are associated with tumor progression both in
      mice and humans. Better knowledge of the mechanisms leading to regulation of FADD
      functions will improve understanding of tumor growth and the immune escape
      mechanisms, and could open a new field for therapeutic interventions.

PMID- 15717930
TI  - A note on generalized Genome Scan Meta-Analysis statistics.
AB  - BACKGROUND: Wise et al. introduced a rank-based statistical technique for meta
      analysis of genome scans, the Genome Scan Meta-Analysis (GSMA) method. Levinson
      et al. recently described two generalizations of the GSMA statistic: (i) a
      weighted version of the GSMA statistic, so that different studies could be
      ascribed different weights for analysis; and (ii) an order statistic approach,
      reflecting the fact that a GSMA statistic can be computed for each chromosomal
      region or bin width across the various genome scan studies. RESULTS: We provide
      an Edgeworth approximation to the null distribution of the weighted GSMA
      statistic, and, we examine the limiting distribution of the GSMA statistics under
      the order statistic formulation, and quantify the relevance of the pairwise
      correlations of the GSMA statistics across different bins on this limiting
      distribution. We also remark on aggregate criteria and multiple testing for
      determining significance of GSMA results. CONCLUSION: Theoretical considerations
      detailed herein can lead to clarification and simplification of testing criteria
      for generalizations of the GSMA statistic.

PMID- 15717931
TI  - Identification of functional SNPs in the 5-prime flanking sequences of human
      genes.
AB  - BACKGROUND: Over 4 million single nucleotide polymorphisms (SNPs) are currently
      reported to exist within the human genome. Only a small fraction of these SNPs
      alter gene function or expression, and therefore might be associated with a cell
      phenotype. These functional SNPs are consequently important in understanding
      human health. Information related to functional SNPs in candidate disease genes
      is critical for cost effective genetic association studies, which attempt to
      understand the genetics of complex diseases like diabetes, Alzheimer's, etc.
      Robust methods for the identification of functional SNPs are therefore crucial.
      We report one such experimental approach. RESULTS: Sequence conserved between
      mouse and human genomes, within 5 kilobases of the 5-prime end of 176 GPCR genes,
      were screened for SNPs. Sequences flanking these SNPs were scored for
      transcription factor binding sites. Allelic pairs resulting in a significant
      score difference were predicted to influence the binding of transcription factors
      (TFs). Ten such SNPs were selected for mobility shift assays (EMSA), resulting in
      7 of them exhibiting a reproducible shift. The full-length promoter regions with
      4 of the 7 SNPs were cloned in a Luciferase based plasmid reporter system. Two
      out of the 4 SNPs exhibited differential promoter activity in several human cell
      lines. CONCLUSIONS: We propose a method for effective selection of functional,
      regulatory SNPs that are located in evolutionary conserved 5-prime flanking
      regions (5'-FR) regions of human genes and influence the activity of the
      transcriptional regulatory region. Some SNPs behave differently in different cell
      types.

PMID- 15717933
TI  - Access to communication technologies in a sample of cancer patients: an urban and
      rural survey.
AB  - BACKGROUND: There is a growing awareness among providers of the symptom burden
      experienced by cancer patients. Systematic symptom screening is difficult. Our
      plan was to evaluate a technology-based symptom screening process using touch
      tone telephone and Internet in our rural outreach cancer program in Indiana.
      Would rural patients have adequate access to technologies for home-based symptom
      reporting? OBJECTIVES: 1) To determine access to touch-tone telephone service and
      Internet for patients in urban and rural clinics; 2) to determine barriers to
      access; 3) to determine willingness to use technology for home-based symptom
      reporting. METHODS: Patients from representative clinics (seven rural and three
      urban) in our network were surveyed. Inclusion criteria were age greater than 18,
      able to read, and diagnosis of malignancy. RESULTS: The response rate was 97%. Of
      416 patients completing the survey (230 rural, 186 urban), 95% had access to
      touch-tone telephone service, while 46% had Internet access (56% of urban
      patients, 38% of rural patients). Higher rates of Internet access were related to
      younger patient age, current employment, and higher education and income. The
      primary barrier to Internet access was lack of interest. Use of the Internet for
      health related activities was less than 50%. The preferred means of symptom
      reporting in patients with internet access were the touch-tone telephone (70%),
      compared to reporting by the Internet (28%). CONCLUSION: Access to communication
      technologies appears adequate for home-based symptom reporting. The use of touch
      tone telephone and Internet reporting, based upon patient preference, has the
      potential of enhancing symptom detection among cancer patients that is not
      dependent solely upon clinic visits and clinician inquiry.

PMID- 15717932
TI  - The PECACE domain: a new family of enzymes with potential peptidoglycan cleavage
      activity in Gram-positive bacteria.
AB  - BACKGROUND: The metabolism of bacterial peptidoglycan is a dynamic process,
      synthases and cleavage enzymes are functionally coordinated. Lytic
      Transglycosylase enzymes (LT) are part of multienzyme complexes which regulate
      bacterial division and elongation. LTs are also involved in peptidoglycan
      turnover and in macromolecular transport systems. Despite their central
      importance, no LTs have been identified in the human pathogen Streptococcus
      pneumoniae. We report the identification of the first putative LT enzyme in S.
      pneumoniae and discuss its role in pneumococcal peptidoglycan metabolism.
      RESULTS: Homology searches of the pneumococcal genome allowed the identification
      of a new domain putatively involved in peptidoglycan cleavage (PECACE,
      PEptidoglycan CArbohydrate Cleavage Enzyme). This sequence has been found
      exclusively in Gram-positive bacteria and gene clusters containing pecace are
      conserved among Streptococcal species. The PECACE domain is, in some instances,
      found in association with other domains known to catalyze peptidoglycan
      hydrolysis. CONCLUSIONS: A new domain, PECACE, putatively involved in
      peptidoglycan hydrolysis has been identified in S. pneumoniae. The probable
      enzymatic activity deduced from the detailed analysis of the amino acid sequence
      suggests that the PECACE domain may proceed through a LT-type or goose lyzosyme
      type cleavage mechanism. The PECACE function may differ largely from the other
      hydrolases already identified in the pneumococcus: LytA, LytB, LytC, CBPD and
      PcsB. The multimodular architecture of proteins containing the PECACE domain is
      another example of the many activities harbored by peptidoglycan hydrolases,
      which is probably required for the regulation of peptidoglycan metabolism. The
      release of new bacterial genomes sequences will probably add new members to the
      five groups identified so far in this work, and new groups could also emerge.
      Conversely, the functional characterization of the unknown domains mentioned in
      this work can now become easier, since bacterial peptidoglycan is proposed to be
      the substrate.

PMID- 15717934
TI  - Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different
      neuromuscular mechanisms: preliminary report.
AB  - BACKGROUND: Vestibular rehabilitation (VR) is a well-accepted exercise program
      intended to remedy balance impairment caused by damage to the peripheral
      vestibular system. Alternative therapies, such as Tai Chi (TC), have recently
      gained popularity as a treatment for balance impairment. Although VR and TC can
      benefit people with vestibulopathy, the degree to which gait improvements may be
      related to neuromuscular adaptations of the lower extremities for the two
      different therapies are unknown. METHODS: We examined the relationship between
      lower extremity neuromuscular function and trunk control in 36 older adults with
      vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance
      measures (gait speed, step length, stance duration and step width), lower
      extremity sagittal plane mechanical energy expenditures (MEE), and trunk sagittal
      and frontal plane kinematics (peak and range of linear and angular velocity),
      were measured. RESULTS: Although gait time-distance measures were improved in
      both groups following treatment, no significant between-groups differences were
      observed for the MEE and trunk kinematic measures. Significant within groups
      changes, however, were observed. The TC group significantly increased ankle MEE
      contribution and decreased hip MEE contribution to total leg MEE, while no
      significant changes were found within the VR group. The TC group exhibited a
      positive relationship between change in leg MEE and change in trunk velocity peak
      and range, while the VR group exhibited a negative relationship. CONCLUSION: Gait
      function improved in both groups consistent with expectations of the
      interventions. Differences in each group's response to therapy appear to suggest
      that improved gait function may be due to different neuromuscular adaptations
      resulting from the different interventions. The TC group's improvements were
      associated with reorganized lower extremity neuromuscular patterns, which appear
      to promote a faster gait and reduced excessive hip compensation. The VR group's
      improvements, however, were not the result of lower extremity neuromuscular
      pattern changes. Lower-extremity MEE increases corresponded to attenuated forward
      trunk linear and angular movement in the VR group, suggesting better control of
      upper body motion to minimize loss of balance. These data support a growing body
      of evidence that Tai Chi may be a valuable complementary treatment for vestibular
      disorders.

PMID- 15717935
TI  - Rapid self-assembly of DNA on a microfluidic chip.
AB  - BACKGROUND: DNA self-assembly methods have played a major role in enabling
      methods for acquiring genetic information without having to resort to sequencing,
      a relatively slow and costly procedure. However, even self-assembly processes
      tend to be very slow when they rely upon diffusion on a large scale.
      Miniaturisation and integration therefore hold the promise of greatly increasing
      this speed of operation. RESULTS: We have developed a rapid method for
      implementing the self-assembly of DNA within a microfluidic system by
      electrically extracting the DNA from an environment containing an uncharged
      denaturant. By controlling the parameters of the electrophoretic extraction and
      subsequent analysis of the DNA we are able to control when the hybridisation
      occurs as well as the degree of hybridisation. By avoiding off-chip processing or
      long thermal treatments we are able to perform this hybridisation rapidly and can
      perform hybridisation, sizing, heteroduplex analysis and single-stranded
      conformation analysis within a matter of minutes. The rapidity of this analysis
      allows the sampling of transient effects that may improve the sensitivity of
      mutation detection. CONCLUSIONS: We believe that this method will aid the
      integration of self-assembly methods upon microfluidic chips. The speed of this
      analysis also appears to provide information upon the dynamics of the self
      assembly process.

PMID- 15717937
TI  - A pragmatic randomised controlled trial of the cost-effectiveness of palliative
      therapies for patients with inoperable oesophageal cancer.
AB  - OBJECTIVES: To compare whether treatment with self-expanding metal stents (SEMS)
      is more cost-effective than treatment with conventional modalities in patients
      with inoperable oesophageal cancer. Quality of life effects were also considered.
      DESIGN: A multicentre pragmatic, randomised controlled trial with health economic
      analysis. SETTING: Seven NHS hospitals selected to represent a cross-section of
      UK hospitals in terms of facilities and staffing. PARTICIPANTS: All patients
      attending the centres with oesophageal cancer deemed unsuitable for surgery were
      assessed for inclusion in the main trial; 217 patients were randomised. A health
      state utilities substudy was also performed in 71 patients who had previously
      received curative surgery for oesophageal cancer. INTERVENTIONS: Eligible
      patients were randomised to one of four treatment groups within two study arms.
      Assessments were performed at enrolment, 1 week following treatment and
      thereafter at 6-weekly intervals until death, with prospective data collection on
      complications and survival. Structured interviews to elicit patient preferences
      to health states and treatments were performed in a substudy. MAIN OUTCOME
      MEASURES: Dysphagia grade and quality of life were examined at 6 weeks. Survival,
      resources consumed from randomisation to death and quality-adjusted life-years
      were also considered. RESULTS: There was no difference in cost or effectiveness
      between SEMS and non-SEMS therapies, and 18-mm SEMS had equal effectiveness to,
      but less associated pain than, 24-mm SEMS. Rigid intubation was associated with a
      worse quality of swallowing and increased late morbidity. Bipolar
      electrocoagulation and ethanol tumour necrosis were poor in primary palliation. A
      survival advantage was found for non-stent therapies, but there was a significant
      delay to treatment. The length of stay accounts for the majority of the cost to
      the NHS. Patients were found to have distinct individual treatment preferences.
      CONCLUSIONS: It was suggested that rigid tubes and 24-mm SEMS should no longer be
      recommended and bipolar electrocoagulation and ethanol tumour necrosis should not
      be used for primary palliation. The choice in palliation would between non-stent
      and 18-mm SEMS treatments, with non-stent therapies being made more available and
      accessible to reduce delay. A multidisciplinary team approach to palliation is
      also suggested. A randomised controlled clinical trial of 18-mm SEMS versus non
      stent therapies with survival and quality of life end-points would be helpful, as
      would an audit of palliative patient admissions to determine the reasons and need
      for inpatient hospital care, with a view to implementing cycle-associated change
      to reduce inpatient stay. A study of delays in palliative radiotherapy treatment
      is also suggested, with a view to implementing cycle-associated change to reduce
      waiting time.

PMID- 15717938
TI  - Impact of computer-aided detection prompts on the sensitivity and specificity of
      screening mammography.
AB  - OBJECTIVES: To determine the value of computer-aided detection (CAD) for breast
      cancer screening. DESIGN: Two sets of mammograms with known outcomes were used in
      two studies. Participants in both studies read the films with and without the
      benefit of a computer aid. In both studies, the order of reading sessions was
      randomised separately for each reader. The first set of 180 films, used in study
      1, included 20 false-negative interval cancers and 40 screen-detected cancers.
      The second set of 120 films, used in study 2, was designed to be favourable to
      CAD: all 44 cancer cases had previously been missed by a film reader and cancers
      prompted by CAD were preferentially included. SETTING: The studies were conducted
      at five UK screening centres between January 2001 and April 2003. PARTICIPANTS:
      Thirty radiologists, five breast clinicians and 15 radiographers participated.
      INTERVENTIONS: All cases in the trial were digitised and analysed using the R2
      ImageChecker version 2.2. Participants all received training on the use of CAD.
      In the intervention condition, participants interpreted cases with a prompt sheet
      on which regions of potential abnormality were indicated. MAIN OUTCOME MEASURES:
      The sensitivity and specificity of participants were measured in both
      intervention and control conditions. RESULTS: No significant difference was found
      for readers' sensitivity or specificity between the prompted and unprompted
      conditions in study 1 [95% confidence index (CI) for sensitivity with and without
      CAD is 0.76 to 0.80, for specificity it is 0.81 to 0.86 without CAD and 0.81 to
      0.87 with CAD]. No statistically significant difference was found between the
      sensitivity and specificity of different groups of film reader (95% CI for
      unprompted sensitivity of radiologists was 0.75 to 0.81, for radiographers it was
      0.71 to 0.81, prompted sensitivity was 0.76 to 0.81 for radiologists and 0.69 to
      0.79 for radiographers). Thirty-five readers participated in study 2. Sensitivity
      was improved in the prompted condition (0.81 from 0.78) but the difference was
      slightly below the threshold for statistical significance (95% CI for the
      difference -0.003 to 0.064). Specificity also improved (0.87 from 0.86); again,
      the difference was not significant at 0.05 (95% CI -0.003 to 0.034). A cost
      effectiveness analysis showed that computer prompting increases cost.
      CONCLUSIONS: No significant improvement in film readers' sensitivity or
      specificity or gain in cost-effectiveness was established in either study. This
      may be due to the system's low specificity, its relatively poor sensitivity for
      subtle cancers or the fact the prompts cannot serve as aids to decision-making.
      Readers may have been better able to make use of the prompts after becoming more
      accustomed to working with them. Prompts may have an impact in routine use that
      is not detectable in an experimental setting. Although the case for CAD as an
      element of the NHS Breast Screening Programme is not made here, further research
      is required. Evaluations of new CAD tools in routine use are underway and their
      results should be given careful attention.

PMID- 15717936
TI  - Assessment of atrial regional and global electromechanical function by tissue
      velocity echocardiography: a feasibility study on healthy individuals.
AB  - BACKGROUND: The appropriate evaluation of atrial electrical function is only
      possible by means of invasive electrophysiology techniques, which are expensive
      and therefore not suitable for widespread use. Mechanical atrial function is
      mainly determined from atrial volumes and volume-derived indices that are load
      dependent, time-consuming and difficult to reproduce because they are observer
      dependent. AIMS: To assess the feasibility of tissue velocity echocardiography
      (TVE) to evaluate atrial electromechanical function in young, healthy volunteers.
      SUBJECTS AND METHODS: We studied 37 healthy individuals: 28 men and nine women
      with a mean age of 29 years (range 20-47). Standard two-dimensional (2-D) and
      Doppler echocardiograms with superimposed TVE images were performed. Standard
      echocardiographic images were digitized during three consecutive cardiac cycles
      in cine-loop format for off-line analysis. Several indices of regional atrial
      electrical and mechanical function were derived from both 2-D and TVE modalities.
      RESULTS: Some TVE-derived variables indirectly reflected the atrial electrical
      activation that follows the known activation process as revealed by invasive
      electrophysiology. Regionally, the atrium shows an upward movement of its walls
      at the region near the atrio-ventricular ring with a reduction of this movement
      towards the upper levels of the atrial walls. The atrial mechanical function as
      assessed by several TVE-derived indices was quite similar in all left atrium (LA)
      walls. However, all such indices were higher in the right (RA) than the LA. There
      were no correlations between the 2-D- and TVE-derived variables expressing atrial
      mechanical function. Values of measurement error and repeatability were good for
      atrial mechanical function, but only acceptable for atrial electrical function.
      CONCLUSION: TVE may provide a simple, easy to obtain, reproducible, repeatable
      and potentially clinically useful tool for quantifying atrial electromechanical
      function.

PMID- 15717939
TI  - Care of pediatric cancers in the developing world: should this be a societal
      priority?

PMID- 15717940
TI  - Epidermal growth factor receptor expression in renal cell carcinoma: rationale
      for therapy with sidling blockade.

PMID- 15717941
TI  - Novel vascular targeting/disrupting agents: combretastatin A4 phosphate and
      related compounds.
AB  - Novel anticancer compounds are being developed that attempt to exploit the unique
      properties of the vascular endothelium, which supplies rapidly dividing
      neoplasms. The goal of these vascular targeting agents (VTAs) or endothelial
      disrupting agents is to cause rapid shutdown of tumor blood supply with
      subsequent tumor death from hypoxia and nutrient deprivation. VTAs are classified
      into two broad categories: biologic therapies or small molecule compounds. A
      variety of VTAs are in early clinical development. These agents have demonstrated
      clinical activity in phase I trials and are being evaluated with cytotoxic
      chemotherapy and radiotherapy.

PMID- 15717943
TI  - Immunotherapy for human cancer using heat shock protein-peptide complexes.
AB  - Heat shock proteins (HSPs) are primordial and abundant molecules expressed in all
      cells. Publications starting in 1984 have shown that immunization of mice, rats,
      and frogs with purified preparations of selected HSPs isolated from cancers leads
      to protective immunity against the cancer used as the source of the HSP. The
      basis of the tumor-specific immunogenicity of these molecules lies not in the
      molecules themselves but in the array of peptides, including antigenic peptides
      chaperoned by them. These experiments and the ideas derived from them form the
      basis of an approach to immunotherapy for human cancer that began in 1995 and is
      now in full swing.

PMID- 15717942
TI  - Clinical experience with monoclonal antibodies to epidermal growth factor
      receptor.
AB  - Recent knowledge about the intermediate steps and final consequences of ligand
      dependent epidermal growth factor receptor (EGFR) activation has clearly
      supported the notion that EGFR plays a fundamental role in regulating the
      proliferation and survival of malignant neoplasms. Among the rationally designed
      target-based therapeutics that are being assessed, those targeting EGFR appear to
      be some of the most clinically relevant. The strategy of using monoclonal
      antibodies (mAbs) to block ligand binding to the extracellular domain of the EGFR
      has led to the development of therapeutics that robustly arrest malignant cell
      proliferation and, in some cases, induce profound tumor regression. The chimeric
      mAb against EGFR, cetuximab, has already been approved by regulatory agencies
      worldwide to treat patients with advanced colorectal cancer. Other mAbs against
      EGFR, particularly panitumumab (ABX-EGF), h-R3, and EMD72000, are in advanced
      stages of clinical development.

PMID- 15717944
TI  - G250: a carbonic anhydrase IX monoclonal antibody.
AB  - G250 or carbonic anhydrase IX (CA IX) is a membrane-associated carbonic anhydrase
      (CA) thought to play a role in the regulation of cell proliferation in response
      to hypoxic conditions and may be involved in oncogenesis and tumor progression.
      G250 refers to a monoclonal antibody (mAb) that was raised by immunization of
      mice with human renal cell carcinoma (RCC) homogenates. The RCC-associated
      transmembrane protein designated G250 has since proven to be identical to tumor
      associated protein MN or CA IX. Previous studies using a mAb against CA IX have
      shown that CA IX is induced constitutively in certain tumor types, but is absent
      in most normal tissues with the exception of epithelial cells of the gastric
      mucosa. Furthermore, previous immunobiochemical studies of malignant and benign
      renal tissues revealed that CA IX was also highly expressed in RCC. Studies on
      tumor-bearing kidneys demonstrate selective uptake of mAb CA IX in antigen
      positive cells versus antigen-negative cells. Furthermore, extraordinarily high
      uptake and the requirement of a low protein dose to obtain tumor saturation with
      respect to tumor targeting occur with mAb CA IX. These studies formed the basis
      of numerous clinical trials aimed at mAb-guided therapy in patients with
      metastatic RCC.

PMID- 15717945
TI  - Novel kinase inhibitors in renal cell carcinoma: progressive development of
      static agents.
AB  - The rapidly expanding knowledge regarding neoplastic diseases is providing a
      plethora of new targets for drug discovery and development as exemplified by
      recent data in renal cell carcinoma. The initial experience with molecularly
      "targeted" agents has demonstrated that development of the newer non-cytotoxic
      agents will provide unique challenges requiring modification of many traditional
      drug development concepts and methods. We discuss recently reported data from a
      few renal cell carcinoma trials with putative cytostatic agents and highlight
      issues that need to be addressed for efficient development of cytostatic agents
      during various phases of clinical development.

PMID- 15717947
TI  - Intensity-modulated radiotherapy: is xerostomia still prevalent?
AB  - Conformal radiation with intensity-modulated radiotherapy (IMRT) is a technique
      that potentially can minimize the dose to salivary glands and thereby decrease
      the incidence of xerostomia. Precise target determination and delineation is most
      important when using salivary gland-sparing techniques of IMRT. Reduction of
      xerostomia can be achieved by sparing the salivary glands on the uninvolved oral
      cavity and keeping the mean parotid gland dose of less than 26 to 30 Gy as a
      planning criterion if the treatment of disease is not compromised and parotid
      function preservation is desired.

PMID- 15717946
TI  - Approaches to optimize the use of monoclonal antibodies to epidermal growth
      factor receptor.
AB  - Preclinical and clinical studies consistently demonstrate the antitumor activity
      of the various monoclonal antibodies (mAbs) that block ligand binding to the
      extracellular domain of the epidermal growth factor receptor (EGFR). However, the
      objective antitumor activities of these agents are disproportionately lower than
      would be expected based on the high rates of expression, overexpression, and
      aberrations of EGFR in human malignancies, particularly carcinomas. Several
      technologic and clinical approaches are being explored to optimize the potency of
      these antibodies, such as humanization of the murine parent molecules, and
      conjugation and widening of the specificity of the mAb. Also, combined therapy
      with the different types of EGFR-interacting or other targeted agents may lead to
      a heightened potential. This review highlights the results of current approaches
      for improvement of the therapeutic indices of these agents.

PMID- 15717948
TI  - Functional imaging in head and neck cancer.
AB  - Functional imaging has become an increasingly important diagnostic tool for head
      and neck cancer, and as its availability increases so will its utilization.
      Positron emission tomography (PET) with the radiotracer 18-fluorodeoxyglucose
      (18FDG) is the most commonly used functional imaging technology, and it has the
      potential to improve the staging and detection of head and neck tumors compared
      with conventional cross-sectional imaging techniques such as CT or magnetic
      resonance imaging. Specifically, PET contributes valuable information for
      localizing a primary tumor in patients with an unknown primary and neck
      metastasis, in the staging of untreated head and neck cancer, in the detection of
      residual disease after definitive radiotherapy or chemoradiotherapy, and in the
      detection of recurrent disease. New technologies have been introduced using the
      combination of CT and PET, which allows exact anatomic correlation with areas of
      increased tracer uptake. In addition, new tracers may allow quantification of
      important cellular processes related to tumor proliferation or identification of
      tumors that may respond to certain targeted therapies. This strategy will
      eventually enable physicians to tailor therapy to molecular characteristics and
      therefore improve outcomes for patients with head and neck cancer.

PMID- 15717951
TI  - Current realities and potential new pathways for cardiology training.

PMID- 15717950
TI  - High-risk non-melanoma skin cancer of the head and neck.
AB  - High-risk non-melanoma skin cancer (NMSC) of the head and neck is difficult to
      manage, given its propensity for regional metastasis, perineural invasion, direct
      parotid invasion, and bony destruction. Management of these tumors demands
      awareness of the characteristics contributing to their recurrence. Recent studies
      emphasize the importance of treatment of the parotid gland and cervical lymph
      nodes to improve locoregional control. A multidisciplinary approach to the
      assessment and treatment of high-risk NMSC is required to provide comprehensive
      care. This review also covers recent advances in the understanding of NMSC
      biology and new approaches in chemoprevention.

PMID- 15717952
TI  - Doctor, can I eat salmon?

PMID- 15717949
TI  - Prevention of head and neck cancer.
AB  - In the vast majority of cases, head and neck cancer is a preventable disease. The
      relationship between tobacco and alcohol and these cancers is well established.
      Despite efforts aimed at reduction of risk factor exposure and early detection
      methods, head and neck cancer remains one of the more common cancers worldwide.
      Recent advances in molecular techniques have provided a framework for future
      targets for early diagnosis and treatment of these malignancies. This review
      provides a summary of recent developments in primary and secondary prevention of
      head and neck cancer and innovative strategies aimed at a reduction in incidence
      and mortality from this disease. The future prevention of head and neck cancer
      will likely require solutions to the widespread use of tobacco products and
      innovative diagnostic techniques leading to improvements in overall survival.

PMID- 15717954
TI  - Mitral valve repair: we must do a better job.
AB  - Mitral valve repair is the only heart valve operation with the potential to
      restore a patient to expected survival. A mandate currently exists for early
      surgical repair of mitral regurgitation before the onset of symptoms and
      significant left ventricular dysfunction. It is based upon a better understanding
      of the natural history of mitral regurgitation, the poor results with medical
      therapy, and the negative impact of abnormal left ventricular size and function,
      and symptoms of long-term survival. It is also based on better operative
      mortality, quality of life, and longevity with repair compared with replacement.
      Despite the existence of this mandate, overall mitral valve repair rates remain
      generally low in the United States. The biggest impact on mitral repair rates is
      likely to come from cardiologists, who would embrace the mandate and insist on
      mitral valve repair and refer their patients to surgeons who consistently and
      successfully repair mitral valves.

PMID- 15717953
TI  - Asymptomatic valvular disease: who benefits from surgery?
AB  - Routine physical examination and noninvasive imaging frequently lead to the
      diagnosis of valvular heart disease in asymptomatic patients. The decision to
      proceed to surgical repair or replacement is based on an informed evaluation of
      the risks of surgery versus those encountered with a nonoperative course. In
      determining whether symptoms are present, stress testing may be helpful, as many
      patients with significant valvular lesions have a tendency to limit their daily
      physical exertion to levels that do not provoke symptoms. The two most feared
      consequences of conservative management, sudden death and permanent myocardial
      damage, are rare in asymptomatic patients with severe aortic stenosis or
      regurgitation. Surgery for asymptomatic aortic stenosis is performed only for
      certain high-risk subsets of patients, including those with left ventricular
      dysfunction, ventricular arrhythmia, and critically small valves. Asymptomatic
      patients with aortic regurgitation and mitral regurgitation should undergo
      surgery if they have systolic dysfunction or marked ventricular enlargement.

PMID- 15717955
TI  - When is concomitant aortic valve replacement indicated in patients with mild to
      moderate stenosis undergoing coronary revascularization?
AB  - Mild to moderate aortic stenosis is a common finding in patients presenting for
      coronary artery bypass grafting (CABG), and its management is controversial.
      However, review of available data suggests a surgical strategy for these
      patients. Recent data demonstrate that 1) progression of aortic stenosis is more
      rapid in those with leaflet calcification; 2) the addition of aortic valve
      replacement to CABG in patients with mild to moderate stenosis does not increase
      hospital mortality when compared with bypass surgery alone; 3) hospital mortality
      for aortic valve replacement after previous bypass surgery has declined in recent
      years; 4) aortic valve replacement places the patient at risk for prosthesis
      related complications; 5) the limited 10-year survival (competing risk of death)
      leaves only a minority of individuals with mild aortic stenosis alive and
      eligible for aortic valve replacement 10 years after bypass surgery; and 6)
      combined aortic valve replacement and CABG confers a survival benefit in those
      with moderate aortic stenosis but not in those with mild aortic stenosis.
      Therefore, in the coronary artery bypass patient with moderate aortic stenosis,
      leaflet calcification, and life expectancy greater than 5 years, concomitant
      aortic valve replacement is advised. In contrast, aortic valve replacement is
      rarely indicated in those with mild aortic stenosis.

PMID- 15717956
TI  - Exercise testing in aortic stenosis.
AB  - Physician-supervised exercise testing in asymptomatic patients with aortic
      stenosis allows an objective assessment of the hemodynamic response to exercise
      and it provides a measure of exercise capacity. Exercise testing cannot be used
      to determine the presence or absence of coronary artery disease, but limited data
      indicate that exercise testing can provide prognostic information. The results of
      such testing can be used to provide an exercise prescription and to reassure the
      patient who might otherwise excessively limit his or her activity.

PMID- 15717957
TI  - Percutaneous approaches to valvular heart disease.
AB  - Percutaneous endovascular therapy has now become a reality. From early balloon
      valvotomy for valvular stenosis, technologies have been developed that allow
      percutaneous replacement of pulmonic and aortic valves and repair of regurgitant
      mitral valves in selected patients. Following extensive investigations in
      animals, early clinical reports have shown successes in selected patients. As
      criteria for patient selection and clinical safety and efficacy trials progress,
      the role of these new technologies in patient care strategy will become better
      understood.

PMID- 15717958
TI  - Single-photon emission computed tomography myocardial perfusion imaging in
      patients with diabetes.
AB  - Diabetes mellitus has reached epidemic proportions, creating a large population
      of people at increased risk for cardiac events. Single-photon emission computed
      tomography myocardial perfusion imaging (SPECT MPI) provides an effective tool to
      accurately diagnose and risk stratify patients with diabetes, similar to patients
      without diabetes. Diabetics, however, are at increased risk for coronary events.
      Diabetics with normal MPI have increased late cardiac events, and even those with
      mild perfusion defects have increased event rates compared with nondiabetics with
      similar perfusion abnormalities. Stress MPI can provide valuable risk
      stratification data for both sexes, with or without diabetes. However, diabetes
      appears to exert a greater relative impact in women than in men. Despite the
      absence of symptoms, the incidence and prevalence of coronary artery disease is
      increased in patients with diabetes. Further studies and research will be needed
      to define the eventual role of SPECT MPI in asymptomatic diabetics.

PMID- 15717959
TI  - Assessment of myocardial viability by nuclear imaging techniques.
AB  - The assessment of myocardial viability has become important in the diagnostic and
      prognostic work up of patients with ischemic cardiomyopathy. Patients with viable
      myocardium may benefit from revascularization in terms of improvement of
      function, symptoms, and prognosis. In contrast, patients without viable
      myocardium do not benefit and should be treated conservatively. Various nuclear
      imaging techniques are available.

PMID- 15717960
TI  - Molecular cardiovascular imaging.
AB  - Imaging with radionuclides has historically played an important role in detection
      of cardiovascular disease as well as in risk stratification and prognostication.
      With the growth of molecular biology have come new therapeutic interventions and
      the requirement for new diagnostic imaging approaches. Noninvasive targeted
      radiotracer-based strategies require the development of new instrumentation to
      meet these needs. This progress has been made possible with the availability of
      many technologic advances, which include dedicated micro single-photon emission
      computed tomography (SPECT) and micro positron emission tomography (PET) hybrid
      systems for small animal imaging. This review is a brief overview on the subject
      of molecular imaging. Basic concepts of molecular imaging are reviewed, followed
      by description of current technologic advances, and current applications to
      evaluate ischemic heart disease and potential therapeutic intervention. The
      emphasis is on the use of both SPECT and PET radiotracers, although other imaging
      modalities are also briefly discussed.

PMID- 15717961
TI  - Quantitative single-photon emission computed tomography imaging.
AB  - Over the past decade, quantitation of cardiac single-photon emission computed
      tomography (SPECT) data, once limited to perfusion assessment, has been extended
      to global and regional function assessment for both the left and the right
      ventricle, as well as to measurement of additional cardiac parameters of
      diagnostic and prognostic interest. A number of commercially available
      quantitative algorithms exist, based on different mathematic operators and with
      varying degrees of automation, that are capable of providing accurate and
      reproducible results. This article describes the many quantitative cardiac SPECT
      measurements available today, defining them in terms of validation, practical
      use, and limitations.

PMID- 15717963
TI  - Urinary frequency: event measure, outcome significance?

PMID- 15717962
TI  - Advances in nuclear imaging for preoperative risk assessment.
AB  - Myocardial perfusion imaging (MPI) is frequently utilized for preoperative risk
      assessment. Results are pertinent for long-term risk. MPI, though most frequently
      applied in intermediate-risk patients, may also be valuable in selected low- and
      high-risk individuals. Coronary stenting may alter the timing of noncardiac
      surgery, which should be considered when performing preoperative risk assessment.

PMID- 15717964
TI  - Laparoscopic radical cystectomy with ileal conduit diversion.
AB  - Remaining the gold standard treatment of muscle-invasive bladder cancer and high
      risk superficial tumors, the radical cystectomy has been translated into a fully
      laparoscopic protocol, actually gaining more and more acceptance worldwide. In
      this article, a transperitoneal antegrade laparoscopic protocol is described for
      radical cystectomy performed in both genders. After removal of the specimen,
      generally through a mini-laparotomy, most of the teams perform the maneuvers for
      urinary diversion through an ileal conduit as an open procedure, although a
      completely laparoscopic procedure has been successfully achieved. Laparoscopic
      cystectomy will face the proof of time if oncologic rules about surgical
      management of transitional cell carcinoma are carefully respected to avoid any
      cell spillage. When obvious laparoscopic advantages for the patients are
      encountered with laparoscopic cystectomy, it seems unlikely that a full
      laparoscopic protocol, including the diversion, may gain wide acceptance; in that
      case, the true laparoscopic benefits would be wasted by unjustified lengthening
      of operative time and by compromising the quality of uretero-ileal anastomoses.

PMID- 15717965
TI  - Nerve-sparing laparoscopic cystectomy.
AB  - Laparoscopic radical cystectomy has been included among the viable options for
      the surgical treatment of muscle-invasive bladder cancer. Even with the minimally
      invasive approach, it must be considered a major surgical intervention and, even
      in experienced hands, it can be associated with a significant percentage of
      complications with a negative impact on overall quality of life, especially in
      terms of continence and sexual potency. According to our Medline search, only two
      papers are available from the literature on laparoscopic and robotic versions of
      nerve- and seminal-sparing cystectomy and nerve-sparing cystectomy, performed
      respectively on three and 17 patients, showing the feasibility and preliminary
      results of those surgical procedures. Therefore, data seem encouraging, but
      further prospective studies are mandatory to correctly assess oncologic and
      functional results in terms of potency and continence maintenance related to
      these innovative techniques.

PMID- 15717966
TI  - Laparoscopic radical cystectomy.
AB  - Laparoscopic radical cystectomy is an emerging technique. It has been proposed as
      an alternative to open radical cystectomy, which is the gold standard treatment
      of muscle-invasive or high-risk superficial bladder cancer. The experience in
      laparoscopic radical cystectomy reported in peer-reviewed journals account for
      approximately 100 cases, with a median longest follow-up of 11.5 months. Safety
      of the technique and cancer control need to be confirmed by a larger cohort of
      patients; however, after an initial analysis, it seems to be equivalent to open
      radical cystectomy. Equivalent does not mean better. Long-term results will
      determine if supposed benefits of laparoscopy overweigh the true increment of
      cost and time.

PMID- 15717967
TI  - Laparoscopic radical cystectomy with continent urinary diversion.
AB  - Laparoscopic radical cystectomy with urinary diversion, although challenging even
      for the skilled laparoscopist, has evolved rapidly throughout the past decade.
      These advances are attributable to a series of well-designed animal studies
      transitioned carefully to humans. Short-term data have shown that this is a
      feasible technique that respects the basic principles of surgical oncology.
      However, the possibility of decreased blood loss, improved visualization, shorter
      hospital stay, and less postoperative pain are balanced against technical
      difficulty, long operative times, and unproved long-term efficacy compared with
      the open gold standard. The goal of this review is to reflect the available
      literature with regard to surgical indications, the current technique in
      evolution, short-term morbidity, and oncologic outcomes.

PMID- 15717968
TI  - Laparoscopic radical cystectomy and urinary diversion.
AB  - Most of the publications regarding laparoscopic radical cystectomy (LRC) have
      reported the institutions' initial experience focusing on technique and
      perioperative results. Increasing experience from major medical centers worldwide
      indicates increasing interest and expertise with LRC. In this manuscript, initial
      laboratory experience, contemporary series, current controversies, and future
      directions of the procedure are discussed. Careful prospective evaluations of
      oncologic and functional outcomes are awaited to define the role of LRC as a
      viable alternative to open radical cystectomy.

PMID- 15717969
TI  - Robot-assisted radical cystectomy and urinary diversion.
AB  - Radical cystectomy remains the standard for muscle-invasive, organ-confined
      urothelial carcinoma of the bladder. With the emergence of minimally invasive
      approaches for the treatment of urologic cancers, technologic advances using
      laparoscopy have led to the development of robotic assistance to increase the
      feasibility of performing this formidable operation. In this article, we describe
      the procedure of robotic-assisted laparoscopic radical cystectomy with urinary
      diversion and review the pertinent literature.

PMID- 15717970
TI  - Nerve-sparing during robotic radical prostatectomy: use of computer modeling and
      anatomic data to establish critical steps and maneuvers.
AB  - This paper is aimed at focusing on the nerve-sparing aspect of the robotic
      prostatectomy. It reviews the existing principles and presents the arguments
      based on robotic fresh cadaver dissections and from actual robotic prostatectomy
      cases.

PMID- 15717971
TI  - Imaging studies after a first febrile urinary tract infection in young children.

PMID- 15717972
TI  - Primary bladder neck dysfunction: an overlooked entity in children.
AB  - Primary bladder neck dysfunction is a non-neurogenic voiding disorder commonly
      diagnosed in young and middle age adult men, but frequently overlooked in
      children. Because these children typically present with lower urinary tract
      symptoms that also are associated with other more common forms of dysfunctional
      voiding, the diagnosis may be missed and treated with a variety of empiric
      modalities that ultimately fail. Although its underlying pathogenesis remains
      debated, the hallmark of the diagnosis is a failure of the bladder neck to
      properly open and allow for unimpeded urine flow. Videourodynamic evaluation is
      the only diagnostic tool that can urodynamically document the obstructive
      pressure/flow parameters of the condition while simultaneously localizing the
      functional obstruction to the bladder neck fluoroscopically. This article reviews
      the clinical and urodynamic findings of this entity in children and adolescents
      and our experience with a adrenergic antagonists, the current approach in medical
      therapy.

PMID- 15717974
TI  - Molecular biology of ureteral bud and trigonal development.
AB  - Advances in molecular biology have provided valuable insight into the development
      of the urinary tract, particularly ureteral bud formation. Reciprocal inductive
      signals between the ureteral bud and growing kidney are crucial for normal
      development. The Wolffian duct serves as the site of origin of the ureteral bud
      and forms distal excretory ducts that are incorporated into the developing
      bladder to become the trigone. Vesicoureteral reflux and renal dysplasia can
      result from abnormal position of the ureteral orifice on the trigone. The
      presumed origin of trigone formation is based largely on evaluation of human and
      animal models performed nearly a century ago. The trigone is thought to develop
      from the mesodermal germ cell layer; however, several recent studies have shown
      that endoderm may be the tissue of origin. This review highlights important
      discoveries in the field of molecular biology as it relates to the development of
      normal and abnormal ureteral bud formation. It also describes the anatomic
      relationship between the developing bud and trigone as it pertains to clinically
      relevant urinary tract anomalies, including recent discoveries that attempt to
      prove the origin of the trigone.

PMID- 15717973
TI  - Mediators of fibrosis and apoptosis in obstructive uropathies.
AB  - Upper urinary tract obstruction, regardless of its cause, often poses a
      significant clinical challenge to the urologist. Renal cellular and molecular
      events that occur in response to upper urinary tract obstruction result in a
      progressive and permanent loss in renal function when left untreated. These
      pathologic changes include the development of renal fibrosis, tubular atrophy,
      interstitial inflammation, and apoptotic renal cell death. Several cytokines and
      growth factors have been identified as major contributors to obstruction-induced
      renal fibrosis and apoptotic cell death, most notably transforming growth factor
      b1 (TGF-b1), angiotensin II, nuclear factor-kB (NF-kB), and tumor necrosis factor
      a (TNF-a). This review examines the challenges of upper urinary tract obstruction
      and the role of these mediators in obstruction-induced renal injury.

PMID- 15717976
TI  - Medication adherence and health care literacy: filling in the gap between
      efficacy and effectiveness.

PMID- 15717975
TI  - Does deflux alter the paradigm for the management of children with vesicoureteral
      reflux?
AB  - The recent approval by the US Food and Drug Administration of Deflux (Q Med,
      Uppsala, Sweden), a particulate biodegradable polymer of dextran, has led to an
      understandable enthusiasm for treating children with vesicoureteral reflux by a
      routinely simple outpatient endoscopic procedure. However, Deflux is but one of a
      variety of particulate substances, both permanent and absorbable, that have been
      used to treat reflux in Europe for well over a decade with varying degrees of
      success. The purpose of this review is to place Deflux in this wider context to
      anticipate what can be expected realistically regarding the efficacy and
      potential hazards of this seductive technique and to make recommendations
      regarding its incorporation, in selected cases, in our therapeutic armamentarium.

PMID- 15717977
TI  - Cognitive rehabilitation in mild Alzheimer's disease.

PMID- 15717978
TI  - Antidepressants in the very old.

PMID- 15717979
TI  - Improving access to geriatric mental health services.

PMID- 15717980
TI  - Bipolar disorder in late life: future directions in efficacy and effectiveness
      research.
AB  - There is a dearth of knowledge regarding the diagnosis and treatment of bipolar
      disorder in late life. Based on a review of the current research on bipolar
      disorder in late life, emerging areas of research were identified: 1)
      methodological challenges in diagnosing bipolar disorder; 2) a lack of guidelines
      for the treatment of bipolar disorder in late life; 3) increased prevalence of
      general medical comorbidities; and 4) a need to improve access to care and social
      support services. The current literature regarding bipolar disorder in late life
      suggests the need for more rigorous studies on accuracy in diagnoses, etiology
      and risk factors, and efficacy studies on pharmacotherapy treatment options.
      However, effectiveness studies that focus on translating research into practice
      also are needed, particularly strategies to monitor and improve the quality of
      care in routine settings and better coordinated medical, psychiatric, and social
      services for older adults with bipolar disorder.

PMID- 15717982
TI  - Cognitive aspects of anxiety and depression in the elderly.
AB  - Although older adults represent the fastest-growing segment of the population, we
      have just begun to understand the nature of anxiety and depression in this age
      group. In this review, current models of anxiety and depression are examined,
      with consideration of similarities and differences between data drawn from
      younger and older adults. Studies that look at the content of specific cognitions
      associated with anxiety, depression, and cognitive processes, such as attention
      and memory, are examined. Consideration is given to areas for clinical
      application and future research.

PMID- 15717981
TI  - Cholinergic dysfunction in vascular dementia.
AB  - Vascular dementia (VaD) is the second most common type of dementia in the elderly
      after Alzheimer's disease (AD). Evidence is presented indicating the occurrence
      of cholinergic dysfunction in VaD, independent from AD. Controlled clinical
      trials of cholinesterase inhibitors (ChEIs) in VaD and in patients with AD plus
      cerebrovascular disease are reviewed. Compared with placebo, ChEI treatment
      improves cognition, behavior, and activities of daily living. Cholinergic
      deficits in patients with VaD may result from ischemia of basal forebrain
      cholinergic nuclei that are irrigated by penetrating arteries that are highly
      susceptible to arterial hypertension, or from ischemic lesions in basal ganglia
      or white matter that sever the extensive cholinergic cortical projections.
      Cholinergic stimulation produces increases in cortical cerebral blood flow that
      may be relevant to the therapeutic effect of ChEIs.

PMID- 15717984
TI  - Memories of childhood abuse in borderline personality disorder.

PMID- 15717985
TI  - Striatal Amphetamine-induced Dopamine Release in Schizotypal Personality
      Disorder.

PMID- 15717983
TI  - Psychiatric aspects of mild cognitive impairment.
AB  - Mild cognitive impairment in the elderly may represent a transitional phase
      between normal aging and early Alzheimer's disease (AD). It recently has been
      recognized as a distinct clinical entity with potentially different cognitive
      subtypes and etiologies. Like AD, studies have shown that psychiatric symptoms
      are more common than in the cognitively normal geriatric population.
      Understanding these symptoms has been recognized as important not only because
      they may impair patient function and caregiver burden, but also these symptoms
      may be relevant to understanding the development of AD in general. This article
      presents current information on psychiatric symptoms in mild cognitive
      impairment, their suggested role in the pathophysiology of AD and future research
      considerations on the subject.

PMID- 15717986
TI  - How does studying schizotypal personality disorder inform us about the prodrome
      of schizophrenia?
AB  - An increasing emphasis in the schizophrenia literature has been on the prodromal
      phase of the illness. The study of schizophrenia spectrum illness, including
      schizotypal personality disorder, has added important insight into the etiology,
      neuropathology, and treatment of schizophrenia, which can facilitate early
      identification, intervention, and perhaps prevention of the illness. The
      heterogeneity of the schizophrenia spectrum makes its definition elusive at best.
      The primary aim of the Cognitive Assessment and Risk Evaluation Program at the
      authors' institution is to combine the current knowledge of clinical and
      demographic risk factors for schizophrenia with the rapidly emerging data on
      vulnerability markers, or endophenotypes, that are associated with schizophrenia.
      The use of brain-based vulnerability markers may help to identify
      neurobiologically and clinically meaningful subgroups within this heterogeneous
      population of individuals in the early stages of schizophrenia. Another important
      aim of the Cognitive Assessment and Risk Evaluation program is to thoroughly
      assess those individuals who have not converted to psychosis to understand
      potential protective factors, reduce the rate of false positives, and decrease
      disability. The current review details a strategy for researching the
      schizophrenia prodrome by using information gained from research in schizotypal
      personality disorder.

PMID- 15717987
TI  - Behavioral genetics of personality.
AB  - Behavioral genetic personality research has moved from findings of genetic and
      environmental effects to new areas. Personality disorders have been included,
      children and adolescents studied, gender effects evaluated, and the importance of
      rater sources investigated. Recently, multivariate methods have been applied to
      disentangle the genetic and environmental latent structure, and investigate
      covariance in mental disorders. Perhaps the most exciting recent developments are
      the investigations of situation variables, the studies of how genotypes influence
      how individuals select themselves into situations and other form of gene
      environment correlations, and how genotype moderates the effect of situations and
      circumstances on behavior (gene-environment interaction). In the future, we will
      learn how personality, partly determined by heredity, influences our entire
      lives. We will better understand what we experience, how we interpret the
      experiences and how to react to them effectively. We will learn how our mental
      lives develop while we interact with the environment, and we will broaden our
      understanding of which genes are coding for mental health and mental disorders.

PMID- 15717988
TI  - Structural models of psychopathy.
AB  - Psychopathy traditionally is defined by a cluster of inferred personality traits
      and socially deviant behaviors. The accepted standard for the reliable and valid
      assessment of psychopathy is the Psychopathy Checklist-Revised (PCL-R). Because
      of its importance in basic and applied research, and in the mental health and
      criminal justice systems, the PCL-R has been subjected to intense scrutiny by
      researchers and clinicians. In this article we discuss issues surrounding its
      structural properties and those of its derivatives. Using factor analysis, item
      response theory, and multidimensional scaling, we propose that the PCL-R and its
      derivatives are underpinned by at least four correlated factors: Interpersonal,
      Affective, Lifestyle, and Antisocial. We argue that attempts to characterize
      antisocial behaviors as merely "downstream" manifestations of more central traits
      are inconsistent with the structural properties of the PCL-R and with evidence
      that the development of traits and actions are interactive and reciprocal. We
      also report new evidence that psychopathy and its factors are dimensional in
      nature, perhaps extreme variants of normal personality traits and behaviors.

PMID- 15717989
TI  - Neuroimaging and personality disorders.
AB  - Within the past several years, neuroimaging research on personality disorders has
      begun to develop. Personality disorders can be thought of as trait-like
      dysfunctional patterns in cognitive, affective, impulse control, and
      interpersonal domains. These domains of dysfunction have been linked to specific
      neural circuits. Developments in brain imaging techniques have allowed
      researchers to examine the neural integrity of these circuits in personality
      disordered individuals. This article reviews the neuroimaging literature on
      borderline personality disorder, antisocial personality disorder (including
      psychopathy) and schizotypal personality disorder. Functional and structural
      studies provide support for dysfunction in fronto-limbic circuits in borderline
      and antisocial personality disorder, whereas temporal lobe and basal striatal
      thalamic compromise is evident in schizotypal personality disorder.

PMID- 15717991
TI  - Clinical applications of hormonal therapy in ovarian cancer.
AB  - The ovary is an endocrine organ and an end organ. Hormones and their receptors
      have been associated with ovarian cancer and may be related to its causation.
      Some data suggest that hormonal therapies may have some effect on ovarian cancer
      in palliative settings. No hormonal therapy is approved by the US Food and Drug
      Administration (FDA) for the treatment of any type of ovarian malignancy nor is
      it listed as an active agent by any of the authoritative compendia. Because of
      the endocrine associations with ovarian cancer, the minimal side effects, and
      demonstrated activity of hormonal therapies in other endocrine-associated
      malignancies, further study is needed.

PMID- 15717990
TI  - Molecular genetics of personality.
AB  - Although initial reports of genetic contributions to personality dimensions were
      promising, continued empirical support remains controversial. The focus has
      largely revolved around polymorphisms of the serotonin transporter gene-linked
      polymorphic region and the D4 dopamine receptor subtype. Equivocal findings
      likely stem from numerous sources including ethnic diversity of subject samples,
      phenotypic characterization of personality traits, and insufficient sample sizes.
      Research has begun to shy away from single gene causation in support of more
      complex polygenic models of personality traits. This search has identified
      numerous other candidate genes including dopamine D2 and D3 receptor subtypes,
      serotonin receptors, and catecholaminergic enzymes, to name a few. This article
      endeavors to review and evaluate the most recent literature within the context of
      this burgeoning field. Some considerations for future research are presented in
      summary.

PMID- 15717992
TI  - Rationale and clinical experience with epidermal growth factor receptor
      inhibitors in gynecologic malignancies.
AB  - The family of epidermal growth factor receptors (EGFRs) is overexpressed in many
      gynecologic malignancies. Extensive preclinical studies of these receptors
      demonstrate that they play an important role in supporting the growth of a wide
      variety of malignancies and that interruption of receptor function or signaling
      from these receptors leads to inhibition of tumor growth or in certain cases
      tumor regression. Recently, many therapeutic agents targeting this receptor have
      entered the clinic and phase II clinical studies have demonstrated activity in
      lung cancer, colon cancer, and head and neck malignancies. Phase II trials of
      both small molecule inhibitors of EGFR and antibody-based inhibitors are underway
      in both cervical and ovarian cancer and emerging data suggests that their
      activity in unselected women with advanced gynecologic malignancies is very
      modest. Recently, molecular analysis of lung cancers has identified that the
      response to small molecule inhibitors of EGFR is highly correlated with
      activating mutations within the EGFR. It is possible that these agents will be
      highly effective in a small subset of patients with gynecologic malignancies
      whose tumors are dependent on EGFR signaling, perhaps through an activating
      mutation in EGFR or its downstream pathway. Until additional research can
      identify the subset of patients most likely to benefit from this targeted
      therapy, treatment for women with gynecologic malignancies with EGFR inhibitors
      should be limited to investigational trials. It is critical that these trials
      have access to tissue of responding and nonresponding patients so to determine
      the rational use of these agents in the treatment of gynecologic malignancies.

PMID- 15717993
TI  - Imatinib mesylate and its potential implications for gynecologic cancers.
AB  - Among gynecologic malignancies, ovarian carcinoma is the most frequent cause of
      death, with the majority of patients presenting at advanced stage. There is a
      high rate of recurrence despite first-line chemotherapy. Sarcoma of the uterus,
      while accounting for a small percent of uterine cancers, is also associated with
      a high-recurrence rate and poor overall survival. Therefore, the development of
      novel treatment strategies is paramount. Imatinib mesylate (Gleevec; Novartis
      Pharmaceuticals Corp., East Hanover, NJ) is a tyrosine kinase inhibitor with
      activity against abl, c-kit, and platelet derived growth factor receptor (PDGFR),
      and is approved for the treatment of chronic myelogenous leukemia and
      gastrointestinal stromal tumor. Preclinical data provides evidence for c-kit and
      PDGFR expression in ovarian epithelial carcinomas and uterine sarcomas and have
      led to clinical trials evaluating the use of imatinib in these malignancies.
      Additionally, inhibition of PDGFR signaling has been proposed as an effective
      mechanism of chemotherapy by lowering tumor interstitial fluid pressure. Recent
      data have also suggested benefit with metronomic scheduling of cytotoxic agents
      at lower doses at more frequent dosing intervals, in combination with other
      targeted therapies. While activity of this agent remains to be established,
      further studies of imatinib in gynecologic malignancies are warranted, to
      demonstrate not only single-agent activity and the enhancement of cytotoxicity of
      other antineoplastic agents.

PMID- 15717994
TI  - Targeted therapies for gynecologic malignancies.
AB  - Despite the enormous promise that targeted therapies hold for patients with
      gynecologic malignancies, it is far too early to recommend any targeted therapy
      outside of a clinical trial. There remains considerable work to be done before
      targeted therapies will have a significant role in this patient population. We
      have learned that different tumor types express different targets, but that the
      mere expression of a target does not necessarily correlate with benefit from the
      use of the targeted agent. No less important is the challenge of determining how
      these agents should be studied in clinical trials, and what constitutes an active
      agent. To document efficacy, targeted agents would hopefully produce response
      (ie, shrinkage of measurable tumor), but as cytostatic agents, the ability to
      delay tumor growth or slow the development of symptoms would be clinically
      important. Combining targeted therapies with cytotoxic agents, radiation, or
      other targeted therapies may be important areas for study, but it is essential to
      demonstrate the additive or synergistic effect of the targeted therapy to an
      already established active one. This review covers strategies used to develop
      targeted agents, reviews available targeted therapies, and suggests potential
      roles in the treatment of gynecologic cancers.

PMID- 15717995
TI  - Incorporating new imaging models in breast cancer management.
AB  - Mammography is the only screening test proven to decrease breast cancer morbidity
      and mortality. Although mammography is an effective screening tool, it does have
      limitations, particularly in women with dense breasts. New imaging techniques are
      emerging to overcome these limitations and enhance cancer detection, improving
      patient outcome. Digital mammography, computer aided detection, breast ultrasound
      and breast magnetic resonance imaging (MRI) are frequently used adjuncts to
      mammography in today's clinical practice. Recent studies have shown that these
      techniques can enhance the radiologist's ability to detect cancer and assess
      disease extent, which is crucial in treatment planning and staging. Positron
      emission tomography (PET) also plays an important role in staging breast cancer
      and monitoring treatment response. Other modalities such as tomosynthesis and MR
      lymphangiography show promise in overcoming the problems related to dense breast
      tissue and the lack of noninvasive methods to assess lymph node status. Imaging
      guided, minimally invasive therapies are also emerging as alternatives to
      surgical biopsy for breast lesions. As imaging techniques improve, the role of
      imaging will continue to evolve with the goal remaining a decrease in breast
      cancer morbidity and mortality.

PMID- 15717996
TI  - Utilizing prognostic and predictive factors in breast cancer.
AB  - In order to make optimal treatment recommendations for patients with early-stage
      breast cancer, it is essential to accurately determine the patient's underlying
      risk of disease recurrence and choose a therapy to which the individual is most
      likely to respond. Lymph node status, tumor size, histopathologic features
      including tumor type and grade, and hormone receptor status are well-accepted
      prognostic factors related to breast cancer. In addition, hormone receptor status
      is a very strong predictor of response to hormonal therapy. However, our
      currently accepted prognostic and predictive factors fall short and there is a
      critical need to more accurately identify those most likely to require or benefit
      from particular therapies. Attention has therefore focused on the determination
      of novel prognostic and predictive factors. The most promising new factor is the
      level of urokinase plasminogen activator and its inhibitor plasminogen activator
      inhibitor. Other putative factors include proliferative rate, the presence of
      lymphatic or vascular invasion, human epidermal growth factor receptor 2 (HER
      2/neu or erbB-2) positivity, the presence of micrometastases in lymph nodes or
      bone marrow, and gene expression profile by microarray analysis, and by RNA-based
      methodology. Data regarding potential new prognostic factors are constantly
      emerging. These studies are frequently challenging to interpret as they are often
      retrospective, based on relatively small numbers of patients, include a mix of
      treated and untreated women, and often do not control for other known prognostic
      factors. Therefore, new data must be interpreted with caution.

PMID- 15717998
TI  - [Surgical decisions for lung cancer: impact on quality of life].

PMID- 15717997
TI  - Management of bone metastases in breast cancer.
AB  - Patients with advanced breast cancer who develop bone metastases suffer an
      ongoing risk of skeletal complications that can have a significant impact on
      their quality of life (QoL). These complications include bone pain, pathologic
      fractures, spinal cord compression, and hypercalcemia of malignancy (HCM), a
      potentially life-threatening condition. Treatment options include radiotherapy to
      palliate bone pain and/or prevent impending fracture, orthopedic surgery to
      prevent or repair fractures, analgesics, and bisphosphonates, which can
      significantly reduce the risk of skeletal complications and delay their onset. Of
      the known bisphosphonates, zoledronic acid is the most potent. Since its
      regulatory approval in the United States and Europe in 2001, zoledronic acid (4
      mg by 15-minute infusion) has become widely used and has replaced pamidronate (90
      mg by 2-hour infusion) as the standard of care for treating bone metastases from
      breast cancer and bone lesions from multiple myeloma. Zoledronic acid has also
      demonstrated significant long-term benefits in randomized trials in prostate
      cancer and other solid tumors, whereas other bisphosphonates have failed. In long
      term, phase III clinical testing, zoledronic acid provided significant treatment
      benefits beyond those of pamidronate in patients with breast cancer and
      demonstrated a safety profile comparable with pamidronate. Therefore, zoledronic
      acid is now recommended from the first diagnosis of bone metastasis. Other
      intravenous bisphosphonates include clodronate and ibandronate. Both are approved
      in Europe, but their efficacy relative to pamidronate and zoledronic acid is not
      known.

PMID- 15717999
TI  - [Factors affecting drug prescription in patients with stable COPD: results from a
      multicenter Spanish study (IDENTEPOC)].
AB  - OBJECTIVE: To determine what factors are associated with prescription of drugs to
      patients with stable chronic obstructive pulmonary disease (COPD). MATERIAL AND
      METHODS: We studied 568 patients with stable COPD. Assessments included
      determination of the severity of dyspnea, body mass index, health-related quality
      of life, and spirometry testing. RESULTS: The forced expiratory volume in 1
      second was significantly associated with prescription of long-acting beta2
      adrenergic agonists (odds ratio [OR]=0.98; 95% confidence interval [CI], 0.96-1)
      and inhaled corticosteroids (OR=0.98; 95% CI, 0.96-1). Quality of life was
      related to administration of short-acting beta2-adrenergic agonists (OR=1.02; 95%
      CI, 1-1.03), long-acting beta2-adrenergic agonists (OR=1.02; 95% CI, 1-1.03),
      ipratropium bromide (OR=1.03; 95% CI, 1-1.04), theophylline drugs (OR=1.02; 95%
      CI, 1-1.03), and inhaled corticosteroids (OR=1.02; 95% CI, 1-1.03). The severity
      of dyspnea was significantly associated with prescription of oral corticosteroids
      (for grade IV dyspnea, OR=15.25; 95% CI, 2.40-97.02). Body mass index was not
      related to drug administration. CONCLUSIONS: Drug prescription in patients with
      stable COPD correlates not only with forced expiratory volume in 1 second but
      also with other parameters such as health-related quality of life and dyspnea.

PMID- 15718000
TI  - [Validation of a respiratory polygraphy system in the diagnosis of sleep apnea
      syndrome].
AB  - OBJECTIVE: To validate a cardiorespiratory polygraphy system (BITMED NGP 140) by
      comparing it to conventional polysomnography in the diagnosis of sleep apnea
      hypopnea syndrome. PATIENTS AND METHODS: Polysomnography and cardio-respiratory
      polygraphy were performed simultaneously on 103 consecutive patients referred
      because of suspected sleep apnea-hypopnea syndrome. The Bland and Altman method
      and intraclass correlation coefficients were used to assess agreement between the
      2 methods of measurement. Receiver operating characteristic (ROC) curves were
      used to calculate the yield of cardiorespiratory polygraphy compared to that of
      conventional polysomnography. RESULTS: Ninety-two valid studies were obtained for
      72 men and 20 women (mean [SD] age: 52.4 [12] years). By the Bland and Altman
      method, the difference between the respiratory event index obtained with the
      BITMED NGP140 and the apnea-hypopnea index (AHI) obtained by conventional
      polysomnography was 7.6 (13.2) in the manual analysis (95% confidence interval
      [CI], 4.9-10.4) and 12 (15.3) (95% CI, 8.8-15.3) in the automatic analysis. For a
      corrected AHI (AH/total time in bed) mean differences were -2.2 (5.9) and 2.4
      (8.2) for manual and automatic analysis. The intraclass correlation coefficients
      were greater than 0.94. The areas under the ROC curves of the respiratory event
      index were greater than 0.97 for all cut points. For an AHI of 30 or higher, the
      best cut-off point determined by manual cardiorespiratory polygraphy analysis was
      27 (sensitivity, 98% and specificity, 98%). For the different cut-off points
      cardiorespiratory polygraphy correctly classified between 92% and 98% of patients
      in both the manual and automatic analyses. CONCLUSIONS: The BITMED NGP140 had
      good agreement with conventional polysomnography for the measurement of
      respiratory events and provided high diagnostic yield.

PMID- 15718001
TI  - [Key words, essential tools for bibliographic research: analysis of usage in
      Archivos de Bronconeumologia for respiratory system knowledge areas].
AB  - OBJECTIVE: To analyze key word usage in Archivos de Bronconeumologia, by
      comparing words used in the journal to those used in the Index Medicus database
      within various respiratory system knowledge areas, and to determine whether usage
      has changed over time. MATERIAL AND METHODS: Original articles published in
      Archivos de Bronconeumologia from 1994 through 2001 were reviewed manually to
      gather the key words used. The list was translated to English and then compared
      to the medical subject heading (MeSH) terms used in the PubMed Browser. RESULTS:
      Seven hundred six original articles published in the study period used a total of
      1163 key words. Matches with MeSH terms were found for 62% (n=46) of the key
      words in smoking research, 48% (n=52) in asthma, 39% (n=82) in respiratory
      insufficiency and sleep disorders, 60% (n=49) in diagnostic and treatment
      techniques, 61% (n=35) in tuberculosis, 65% (n=87) in nontuberculous infections,
      61% (n=121) in oncology, 60% (n=37) in circulation, 55% (n=47) in pleural
      diseases, 48% (n=21) in pathophysiology, and 64% (n=68) in interstitial diseases.
      We did not see a clear tendency in the evolution of the journal's key word usage
      for the knowledge areas analyzed during the study period. The percentage of
      matching key words held steady around 50% over the last 3 years. CONCLUSIONS:
      Respiratory system key words in the knowledge areas we investigated are used
      correctly in Archivos de Bronconeumologia only about 50% of the time.

PMID- 15718002
TI  - [Agreement between type of lung resection planned and resection subsequently
      performed on lung cancer patients].
AB  - OBJECTIVE: To assess agreement between planned lung resections and the type
      subsequently performed on a series of patients, to assess whether tumor location
      (central or peripheral) affected the degree of discrepancy, and, in the case of
      unscheduled pneumonectomies, to examine why the planned resection had to be
      extended. METHOD: Prospective, observational clinical study of 199 patients
      scheduled for lung cancer surgery. Tumors were preoperatively classified as
      central or peripheral, and the type of operation planned--lobectomy (or
      bilobectomy) or pneumonectomy--was compared with the operation finally performed.
      Rates of agreement and Wilks' lambda statistic were calculated. RESULTS: Twenty
      unscheduled pneumonectomies were performed. Agreement between planned and
      performed operations was found in 86.9% of cases (76.9% in central tumors and
      95.4% in peripheral tumors). Wilks' lambda statistic was 0.38 (0.42 for central
      tumors and 0.17 for peripheral tumors). Seven unscheduled pneumonectomies were
      performed due to hilar node involvement. CONCLUSIONS: The resections performed
      differed from the resections initially planned in 13% of the bronchial carcinoma
      operations, in most cases because the planned lobectomy had to be converted to
      pneumonectomy, a situation which occurred more often with central tumors and was
      more often due to direct invasion of anatomic structures rather than hilar
      spread.

PMID- 15718003
TI  - [Primary hyperhidrosis and anxiety: a prospective preoperative survey of 158
      patients].
AB  - OBJECTIVE: To determine the location of hyperhidrosis, the accompanying signs and
      symptoms, and patient anxiety assessed on 2 scales and standardized psychometric
      instruments. PATIENTS AND METHODS: A prospective study of patients with
      hyperhidrosis was carried out between September 1, 2001 and June 30, 2003 with a
      self-administered preoperative questionnaire. The variables studied included the
      location of hyperhidrosis, the accompanying signs and symptoms, and the self
      reported degree of anxiety and perception of its effect on daily life assessed by
      the State-Trait Anxiety Inventory (STAI) and a questionnaire designed in our
      department. RESULTS: Palmar hyperhidrosis was reported by 93.6% of patients,
      plantar by 70.2%, axillary by 66.4%, facial by 12.1%, groin by 8.2%, chest by 5%,
      and abdominal by 2%. While more than 50% of the patients reported facial blushing
      and palpitations as accompanying signs and symptoms, approximately 30%
      experienced epigastric pain, trembling, and headaches. Over half of the patients
      reported that their anxiety was incapacitating, and a mere 1.2% experienced none
      at all. STAI scores were similar to those of the general population whereas
      scores on our department's questionnaire reflected those of the self-reported
      anxiety ratings. CONCLUSIONS: Primary hyperhidrosis is a disorder in which
      excessive sweating occurs mainly, but not exclusively, on the palms. The
      condition is accompanied by signs and symptoms typical of autonomic nervous
      system hyperactivity and by a degree of anxiety that has an incapacitating effect
      on normal life, although that anxiety is not detected by the STAI questionnaire
      alone.

PMID- 15718004
TI  - [Pulmonary manifestations of inflammatory bowel disease].

PMID- 15718005
TI  - [Small cell lung cancer and cancer-associated retinopathy].
AB  - We report the case of a patient who presented with cancer-associated retinopathy
      and small cell carcinoma of the lung, which was treated surgically because the
      initial diagnostic biopsy finding was squamous cell carcinoma. The patient then
      underwent chemotherapy and radiation therapy. We discuss the characteristics and
      pathogenesis of this paraneoplastic syndrome as well as its association with the
      lung tumor's aberrant production of a protein that competes with retinal
      recoverin at the photoreceptors of the retinal cone.

PMID- 15718006
TI  - [Malignant melanoma of the lung: is it easy to determine its origin?].
AB  - Malignant melanoma involving the respiratory tract is nearly always metastatic.
      True primary tumors are very rare, and only approximately 28 cases have been
      reported in the literature. Extensive clinical and histopathological examinations
      are needed to ascertain that the lung is the primary site. We present the case of
      a 67-year-old man with an apparent primary malignant melanoma of the lung in the
      right lower lobe. We also review the literature.

PMID- 15718007
TI  - [Surgical treatment of spontaneous pneumothorax].

PMID- 15718008
TI  - [Cardiac angiosarcoma presenting as hemothorax].

PMID- 15718009
TI  - [Deep venous thrombosis: therapeutic considerations].

PMID- 15718010
TI  - [Upper limb deep venous thrombosis. Risk factors, outcome, and posthrombotic
      syndrome].
AB  - OBJECTIVE: Our objective was that of describing a series of episodes of upper
      limb deep venous thrombosis, with special emphasis on the incidence of
      posthrombotic syndrome and its impact in the quality of life of the patients.
      METHODS: 33 episodes (29 patients) of upper limb deep venous thrombosis were
      studied, between January 1995 and January 2002; episodes until September 1999 (18
      episodes) were considered retrospectively while those which took place starting
      in this date (15 episodes) were considered prospectively. In all, 24 patients
      were cared in hospital clinic. It was possible to obtain complete data in 16
      cases, in which evolution toward posthrombotic syndrome, venous
      revascularization, and impact of the pathological process in the global quality
      of life of patients were studied. RESULTS: Average age of patients was 58.9
      years. In 25 episodes (75.8%) some risk factor for venous thrombosis existed, the
      presence of a venous catheter being the most frequent. Subclavian axillary
      affectation was predominant (18 episodes, 55%) and in the left side (25 episodes,
      76%). Twenty-eight episodes were diagnosed with echography (84.8%). Mean D-dimers
      concentration (N = 16) was 1,046 ng/ml (standard deviation [SD]: 826.9). One of
      the episodes (3%) was associated to lung thromboembolism. Treatment consisted on
      the administration of low molecular weight heparin during the acute phase in 70%
      of the cases. In 13 episodes (39%) additional treatment of thrombosis
      (endovascular in most) was carried out. In 29 episodes (88%) chronic treatment
      was administered with acenocoumarol, while in 4 episodes (12%) the administration
      of low molecular weight heparin was kept. No patient died during hospitalization.
      In 15 patients (52%) control of revascularizacion was performed. We detected
      complete revascularization in 6 patients (40%), revascularization with collateral
      circulation in 4 patients (27%), partial revascularization in other 4 patients
      (27%) and presence of permeability but with expansion and tortuosity of deep
      venous system in 1 case (6%). Posthrombotic syndrome was considered mild or
      nonexistent in 10 patients (62.5%) and moderate in 6 patients (37.5%). Quality of
      life of patients with moderate posthrombotic syndrome was significantly worse
      than that of patients with mild posthrombotic syndrome (73 vs 90, p < 0.035).
      CONCLUSIONS: Most of upper limb deep venous thrombosis are associated to the use
      of intravenous catheters. Echography is the primary diagnostic technique. At the
      time of the diagnosis, patients tend to show elevation in D-dimers levels.
      Evolution toward posthrombotic syndrome is frequent; this syndrome does not use
      to be serious but indeed influences the quality of life of patients.

PMID- 15718011
TI  - [Clinical recurrence of multinodular goiter after surgery. A multivariate study
      on the risk factors].
AB  - INTRODUCTION: In multinodular goiter there is no consensus on which is the most
      adequate surgical technique, since although the techniques with partial resection
      show lower risk of complications they are associated with a higher risk of
      recurrences. The objective of this study is to define the risk factors for
      recurrence of multinodular goiters after surgery in a series with a mean
      postoperative follow-up higher than 12 years. PATIENTS AND METHOD: 231
      multinodular goiters with partial thyroid surgery are analyzed. The recurrence is
      assessed through clinical exploration, and is confirmed with echography. The
      variables analyzed are age, sex, family history of thyroid pathology, residence
      in goitrogenic areas, asymptomatic hyperthyroidism, compression syndromes,
      intrathoracic extension of goiter, surgeon experience with endocrine surgery,
      weight of the thyroid, and surgical technique, chi2 test, Student's t test and a
      logistic regression test are applied. RESULTS: After a mean postoperative follow
      up of 152 +/- 71 months 67 goiters (29%) showed recurrence with a mean time for
      recurrence of 85 +/- 67 months. Risk factors detected in the multivariate study
      were youngest age, surgeon's lack of experience in endocrine surgery, and the
      surgical technique. Forty-six patients (69%) were operated because of recurrence,
      most of them by surgeons experienced in endocrine surgery. Thyroidectomy was
      completed in all cases, and two definitive postoperative complications occurred.
      CONCLUSIONS: The index of clinical recurrences is high and increases with the
      progression; primary risk factors are age, surgeon's experience, and surgical
      technique. The implication is that partial resection techniques should be carried
      out by surgeons with experience and there should be avoided in young patients.

PMID- 15718012
TI  - [Limited application of prevention measures in patients with diabetes mellitus
      type 2 and coronary artery disease in Spain. DIETRIC study].
AB  - INTRODUCTION AND OBJECTIVES: Diabetes is a disease with high prevalence that
      involves high mortality. The control of risk factors reduces the cardiovascular
      complications. The objective of this study is to define the control degree of
      cardiovascular risk factors in patients with diabetes and coronary artery
      disease. METHODS: In DIETRIC study 628 patients with diabetes type 2 and coronary
      artery disease have been included with the aim to study the antianginous effect
      of trimetazidine. Patients were studied basally with clinical history, physical
      exploration, laboratory testing, ECG and exercise test, with 6-month follow-up.
      In this article the profile of cardiovascular risk and the level of control of
      the risk factors in the basal study are analyzed. RESULTS: More than 80% of
      patients showed excess weight or obesity, 73% dyslipemia and 59% hypertension.
      More than 60% of patients showed 3 or more related risk factors. Only 15% had
      adequate control of blood pressure, and the control of diastolic pressure (55%)
      was most frequent than that of systolic (17%). Only 7.5% had adequate control of
      plasma lipids. Many patients did not take drugs to reduce mortality, as aspirin
      and statins. CONCLUSIONS: Most of these diabetic patients with coronary artery
      disease do not have adequate control of risk factors. A limited use of drugs that
      have proven to reduce cardiovascular mortality in these patients is observed.

PMID- 15718013
TI  - [Cost-effectiveness of computerized axial tomography in the diagnosis of
      traditional clinical picture of fever of unknown origin].
AB  - Diagnostic strategy in fever of unknown origin has been changing in recent
      decades. The objective of this study is to define the role of thoracoabdominal
      computerized axial tomography in the first diagnostic stage. A sample of 24
      patients with classical fever of unknown origin from our hospital Internal
      Medicine department was selected between January 1995 and December 2002. Cost
      effectiveness of diagnostic thoracoabdominal computerized axial tomography
      compared to that of abdominal echography was analyzed; the information obtained
      with both diagnostic techniques for the final diagnosis was also evaluated.
      Computerized axial tomography contributed data suggestive of the diagnosis in 10
      of 24 patients (41.7%); abdominal echography only gave orienting information to
      the diagnosis in 2 cases (8%). In 9 (90%) of the 10 patients with computerized
      axial tomography specific alterations, a conclusive definitive diagnosis (with
      analysis of biological sample) was possible. Accordingly, the use of this
      technique is justified at the beginning of the study of the classical fever
      unknown origin in order to orient the clinician to resort to other more directed
      and specific diagnostic techniques and with higher diagnostic cost-effectiveness.

PMID- 15718014
TI  - [Inhaled steroids in the treatment of COPD].

PMID- 15718015
TI  - [Diagnostic strategies in spondylarthropaties].

PMID- 15718016
TI  - [Pain treatment in cancer patients].

PMID- 15718017
TI  - [Self-limited abdominal pain: diagnostic imaging].

PMID- 15718018
TI  - [A 63-year-old male with hemoptysis, pleuritic pain, and lung mass].

PMID- 15718019
TI  - [Low-back pain and "Petit's hernia"].

PMID- 15718020
TI  - [A 40-year-old male with cerebrovascular accident without sequelae].

PMID- 15718021
TI  - [Disseminated Pneumocystis carinii in a patient treated with immunosuppressive
      drugs].

PMID- 15718022
TI  - [Diogenes syndrome: neuroradiology findings in white matter. Organic basis of
      self-care alterations in elderly people].

PMID- 15718023
TI  - [Fatal digitalis poisoning].

PMID- 15718024
TI  - Contamination of chicken carcasses in Gauteng, South Africa, by Salmonella,
      Listeria monocytogenes and Campylobacter.
AB  - The presence of the foodborne pathogens, Salmonella spp., Listeria monocytogenes
      and Campylobacter spp., on 99 fresh and frozen chicken carcasses sourced from
      various retailers in Gauteng, South Africa, was investigated. Using culture
      methods, 60.6% of the carcasses were found to be contaminated with one or more
      pathogens, with 19.2%, 19.2% and 32.3% of the carcasses being found to harbour
      Salmonella, L. monocytogenes and Campylobacter, respectively. The extent of
      contamination with one or more pathogens was not significantly different (p>0.1)
      between fresh or frozen samples or between samples from butcheries, supermarkets
      or street vendors. Significantly more (p<0.1) fresh carcasses from butcheries
      than from other outlets were contaminated with Salmonella, while more fresh
      carcasses from supermarkets were contaminated with Campylobacter. The proportion
      of carcasses with L. monocytogenes from all sources were similar. Polymerase
      chain reaction (PCR) results indicate an even higher extent of pathogen
      contamination, but the PCR techniques need to be further refined before they can
      be used routinely.

PMID- 15718025
TI  - Interactions of Escherichia coli O157:H7, Salmonella typhimurium and Listeria
      monocytogenes plants cultivated in a gnotobiotic system.
AB  - The growth and persistence of Escherichia coli O157:H7, Salmonella typhimurium
      and Listeria monocytogenes on a diverse range of plant types over extended
      cultivation periods was studied. When introduced on the seed of carrot, cress,
      lettuce, radish, spinach and tomato all the pathogens became rapidly established
      shortly after germination, attaining cell densities of the order of 5.5-6.5 log
      cfu/g. In general, Es. coli O157:H7 and L. monocytogenes became established and
      persisted at significantly higher levels on seedlings (9 days post-germination)
      than Salmonella. Es. coli O157:H7 became internalized in cress, lettuce, radish
      and spinach seedlings but was not recovered within the tissues of mature plants.
      Internalization of Salmonella was also observed in lettuce and radish but not
      cress or spinach seedlings. In contrast, L. monocytogenes did not internalize
      within seedlings but did persist on the surface of plants throughout the
      cultivation period. Co-inoculation of isolates recovered from the rhizosphere of
      plants did not significantly affect the numbers or persistence of human
      pathogens. The only exception was with Enterobacter cloacae, which reduced Es.
      coli O157:H7 Ph1 and L. monocytogenes levels by ca. 1 log cfu/g on lettuce. With
      the bioluminescent phenotype of Es. coli O157:H7 Ph1, it was demonstrated that
      the human pathogen became established on the roots of growing plants. Scanning
      electron micrographs of root seedlings suggested that Es. coli O157:H7 Ph1
      preferentially colonized the root junctions of seedlings. It is proposed that
      such colonization sites enhanced the persistence of Es. coli O157:H7 on plants
      and facilitated internalization within developing seedlings. The results suggest
      that the risk associated with internalized human pathogens in salad vegetables at
      harvest is low. Nevertheless, the introduction of human pathogens at an early
      stage of plant development could enhance their persistence in the rhizosphere.
      The implications of the study with regards to on-farm food safety initiatives are
      discussed.

PMID- 15718026
TI  - Inactivation of Escherichia coli, Listeria innocua and Saccharomyces cerevisiae
      in relation to membrane permeabilization and subsequent leakage of intracellular
      compounds due to pulsed electric field processing.
AB  - Membrane permeabilization, caused by pulsed electric field (PEF) processing of
      microbial cells, was investigated by measurement of propidium iodide (PI) uptake
      with flow cytometry. Inactivation of Escherichia coli, Listeria innocua and
      Saccharomyces cerevisiae was determined by viable counts, and leakage of
      intracellular compounds, such as ATP and UV-absorbing substances, was measured in
      the extracellular environment. Electrical field strength and pulse duration
      influenced membrane permeabilization of all three tested organisms of which S.
      cerevisiae was the most PEF sensitive, followed by E. coli and L. innocua. It was
      shown by viable counts, PI uptake and leakage of intracellular compounds that L.
      innocua was the most resistant. Increased inactivation corresponded to greater
      numbers of permeabilized cells, which were reflected by increased PI uptake and
      larger amounts of intracellular compounds leaking from cells. For E. coli and L.
      innocua, a linear relationship was observed between the number of inactivated
      cells (determined as CFU) and cells with permeated membranes (determined by PI
      uptake), with higher number of inactivated cells than permeated cells. Increased
      leakage of intracellular compounds with increasing treatment severity provided
      further evidence that cells were permeabilized. For S. cerevisiae, there was
      higher PI uptake after PEF treatments, although very little or no inactivation
      was observed. Results suggest that E. coli and L. innocua cells, which took up
      PI, lost their ability to multiply, whereas cells of S. cerevisiae, which also
      took up PI, were not necessarily lethally permeabilized.

PMID- 15718027
TI  - Molecular analysis of the gene cluster involved in the production and secretion
      of enterocins 1071A and 1071B and of the genes responsible for the replication
      and transfer of plasmid pEF1071.
AB  - Plasmid pEF1071 (9328 bp), bearing the structural genes of enterocins 1071A and
      1071B, had been sequenced and nine genes were identified. The genes responsible
      for the production and transfer of enterocins 1071A and 1071B are arranged in two
      operons. The first operon (EntABI) contains the genes ent1071A, ent1071B and entI
      that encodes enterocin 1071A, enterocin 1071B and immunity to these bacteriocins,
      respectively. The second operon (EntTD) contains two genes, viz. abc (also named
      entT) and entD, encoding a putative ABC transporter (697 aa) and an accessory
      protein (697 aa), respectively. Three genes (mobC, mobA and mobX), situated
      downstream of the second operon, encode proteins of 127, 346 and 224 amino acids,
      respectively, and are presumably involved in the mobilization of plasmid pEF1071.
      The ninth gene was identified as a putative repA gene encoding a protein of 327
      amino acids. The transcription initiation sites of the genes ent1071A, abc, mobA,
      mobX and repA were determined by primer extension. By inserting the cat gene into
      the ent1071B gene, and thereby disrupting the operon structure, we have shown
      that bacteriocins Ent1071A and Ent1071B act independently against target
      bacteria.

PMID- 15718028
TI  - Rapid detection of Escherichia coli O157:H7 by immunomagnetic separation and real
      time PCR.
AB  - A method combining immunomagnetic separation (IMS) and real-time (5'-nuclease)
      PCR was developed to detect Escherichia coli O157:H7. Monoclonal antibody
      specific for the E. coli O157 antigen was added to protein A-coated magnetic
      particles to create antibody-coated beads. The beads specifically captured E.
      coli O157:H7 from bacterial suspensions. The cells were eluted from the beads and
      lysed by heating; the eluate was then assayed by real-time PCR, using primers and
      probe specifically targeting the eaeA gene of E. coli O157:H7. Approximately 50%
      of the cells in suspension were captured by the beads and detected by real-time
      PCR. No cross-reactivity was detected when other strains of E. coli were tested.
      This method was applied to detect E. coli O157:H7 from ground beef. Both cell
      capture efficiency and real-time PCR efficiency were reduced by meat-associated
      inhibitors. However, we were still able to detect up to 8% of E. coli O157:H7
      from inoculated ground beef samples. The detection sensitivity varied among
      ground beef samples. The minimum detection limit was <5x10(2) cells ml(-1) for
      suspensions of E. coli O157:H7 in buffer and 1.3x10(4) cells g(-1) for E. coli
      O157:H7 in ground beef. The combination of IMS and real-time PCR results in
      rapid, specific and quantitative detection of E. coli O157:H7 without the need
      for an enrichment culture step.

PMID- 15718029
TI  - Reducing Salmonella on cantaloupes and honeydew melons using wash practices
      applicable to postharvest handling, foodservice, and consumer preparation.
AB  - Washing conditions that included a soak or brush scrub were evaluated for removal
      of Salmonella from the surface of smooth (honeydew) or complex (cantaloupe) melon
      rinds. Melon rinds were spot-inoculated onto a 2.5 cm2 area of rind (squares)
      with approximately 6.0 log(10) CFU/square of an avirulent nalidixic acid
      resistant strain of Salmonella typhimurium. Melons were washed by immersion in
      1500 ml of water or 200 ppm total chlorine and allowed to soak or were scrubbed
      over the entire melon surface with a sterile vegetable brush for 60 s. Inoculated
      sites, uninoculated sites ("next to" sites) that were adjacent to inoculated
      sites, and sites on the side of the melon opposite (remote sites) the inoculated
      site were excised and pummeled in a stomacher for 2 min prior to plating onto
      tryptic soy or bismuth sulfite agar supplemented with 50 microg/ml nalidixic
      acid. S. typhimurium was reduced on the rind of cantaloupe by 1.8 log CFU/melon
      after soaking for 60 s in 200 ppm total chlorine, which was significantly better
      than the 0.7 log CFU/melon achieved with soaking in water. For both water and 200
      ppm total chlorine, scrubbing with a vegetable brush was shown to be
      significantly (0.9 log CFU/cantaloupe) more effective than soaking alone. When
      honeydew melons were soaked or scrubbed in water, reductions of 2.8 log CFU/melon
      or >4.6 log CFU/melon (four of five samples), respectively, were observed.
      However, when water treatments were used, the presence of Salmonella-positive
      "next to" and remote sites indicated that bacteria were spread from inoculated
      site on the rind to uninoculated sites either through the rinse water (40-70
      CFU/ml of Salmonella) or scrub brush (400-500 CFU/brush). Transfer to other sites
      occurred more often with cantaloupe than honeydew melons. This transfer was
      eliminated when 200 ppm total chlorine was used. When 200 ppm total chlorine was
      used, Salmonella could not be detected in the water or on the scrub brush. For
      optimal microbial removal in food service and home settings, melons should be
      scrubbed with a clean brush under running water. However, to ensure the benefits
      of brushing, instructions for cleaning and sanitizing brushes must also be
      emphasized. For food service settings where concentration and pH can be
      adequately measured, the use of chlorinated water may provide additional benefit.

PMID- 15718030
TI  - Moulds and yeasts in fresh and minimally processed vegetables, and sprouts.
AB  - A limited survey of fresh and minimally processed vegetables, and sprouts was
      conducted in the Washington, DC area to determine if potentially toxigenic and
      pathogenic fungi were present in these commodities. Thirty-nine ready-to-eat
      salads, 29 whole fresh vegetables and 116 sprout samples (bean, alfalfa,
      broccoli, crunchy, garlic, spicy, onion, clover, lentil and multi-seed sprouts)
      were purchased from 13 local supermarkets and tested for yeast and mould counts
      as well as the presence of toxigenic moulds. Yeasts were the most prevalent
      organisms found in these samples, at levels ranging from less than 100 to
      4.0x10(8) cfu/g. Mould counts generally ranged from less than 100 to 4.0x10(4)
      cfu/g. Two crunchy sprout samples, however, contained unusually high numbers of
      Penicillium (1.1x10(8) and 1.3x10(8) cfu/g), two alfalfa sprout samples contained
      Geotrichum populations about 10(6) cfu/g, and two alfalfa sprout samples had
      Cladosporium counts higher than 2.5x10(5) cfu/g. The most common moulds found in
      fresh and minimally processed vegetables were Cladosporium, Alternaria and
      Penicillium; less common was Geotrichum. The most frequently isolated moulds from
      sprouts were Alternaria, Cladosporium, Penicillium, and Phoma. Phoma was
      especially common in alfalfa sprouts. Fusarium, Rhizopus, Mucor, and Geotrichum
      were isolated less often.

PMID- 15718031
TI  - Inactivation of Escherichia coli O157:H7 during storage or drying of apple slices
      pretreated with acidic solutions.
AB  - Inactivation of Escherichia coli O157:H7 was evaluated on inoculated apple slices
      without pretreatment or pretreated by immersing in water or acid solutions
      commonly used to help retain apple color during dehydration, then stored at
      ambient temperature or dried for 6 h. Half-ring slices (0.6 cm thick) of peeled
      and cored Gala apples were inoculated by immersion for 30 min in a three-strain
      composite inoculum of E. coli O157:H7 (7.8-8.0 CFU/g). Inoculated slices received
      (1) no pre-drying treatment (control); or a 10-min immersion in solutions of (2)
      sterile water, (3) 2.8% ascorbic acid, (4) 1.7% citric acid, (5) 50% commercial
      lemon juice, or (6) 50% commercial lemon juice with preservatives. Drained slices
      were placed in sterile plastic bags and stored at room temperature (25+/-2
      degrees C) for up to 6 h or dehydrated (62.8 degrees C) for up to 6 h. Samples
      were plated on tryptic soy agar (TSA) and sorbitol MacConkey agar (SMAC) for
      direct enumeration of surviving bacteria at various time intervals. Immersion in
      sterile water or acidic solutions caused initial bacterial reductions of 0.9-1.3
      log CFU/g on apple slices. Between 0 and 6 h of storage at room temperature,
      slices dipped in acidic solutions showed minor changes in bacterial populations (
      0.2 to +0.6 log CFU/g) compared to a 1.1 log CFU/g increase for slices dipped in
      sterile water. The no treatment samples (control) showed an increase in bacterial
      populations of 1.3-1.5 CFU/g over the 6-h holding time. For apple slices dried at
      62.8 degrees C, bacterial populations were reduced by 2.5 (SMAC) and 3.1 (TSA)
      log CFU/g in the control (no pre-drying treatment) samples following 6 h
      dehydration. The slices immersed in sterile water showed a 5.8 (SMAC) and 5.1
      (TSA) reduction after 6 h of dehydration. In contrast, after 6 h of dehydration
      bacterial populations on the four acid-pretreated products were reduced by 6.7
      7.3 log CFU/g. The results showed that acidic treatment alone was not effective
      in destroying E. coli O157:H7 on apple slices but did inhibit growth of the
      organism during holding before drying. However, pretreatment of the apple slices
      with common household acidulants enhanced destruction of E. coli O157:H7 during
      drying compared to slices dried without treatment.

PMID- 15718032
TI  - Effects of environmental stresses on the activities of the uspA, grpE and rpoS
      promoters of Escherichia coli O157:H7.
AB  - Heat shock proteins and RNA polymerase sigma factor play an important role in
      protecting cells against environmental stresses, including starvation, osmotic
      and oxidative stresses, and cold shock. In this study, the effect of
      environmental stresses on activity of the auto-fluorescent Escherichia coli
      O157:H7 generated by the fusion of gfp(uv) to E. coli uspA, grpE and rpoS
      promoters were examined. Osmotic shock caused about a 4-fold increase in green
      fluorescence of E. coli O157:H7 harboring uspA::gfp(uv) or rpoS::gfp(uv) at 37
      degrees C and room temperature whereas osmotic shock at 5 degrees C did not
      induce green fluorescence. When starved, E. coli O157:H7 possessing grpE::gfp(uv)
      was more sensitive for evaluating stress at low temperature while uspA::gfp(uv)
      was better suited for detecting the stress response at higher temperature. The
      uspA, grpE and rpoS promoters were up-regulated to varying degrees by stresses
      commonly encountered during food processing.

PMID- 15718033
TI  - Campylobacter spp. in New Zealand raw sheep liver and human campylobacteriosis
      cases.
AB  - Sheep liver samples were tested for the presence and numbers of Campylobacter
      jejuni and C. coli during both spring and autumn. Over the same period, isolates
      were obtained from human clinical cases from the same geographical area as where
      the food samples were purchased. A subset of the C. jejuni isolates was typed by
      both Penner serotyping and pulsed field gel electrophoresis using the restriction
      enzyme SmaI, to estimate the proportion of liver isolate types that were also
      isolated from human cases of campylobacteriosis. Of the 272 liver samples tested,
      180 (66.2%) contained Campylobacter. Most of the positive samples contained <3
      MPN/g of the organism, and only 12 (6.7%) were contaminated at a level exceeding
      100 MPN/g. A total of 180 C. jejuni isolates were obtained from sheep liver and
      another 200 from human faeces. Of these, 212 isolates were randomly selected for
      typing, half from raw liver and half from human faeces. More than half (61.1%) of
      the 106 C. jejuni isolates from liver were of subtypes that were also isolated
      from human cases. While the C. jejuni present in sheep liver were mostly of
      subtypes also isolated from human cases, the significance of this food as a
      vehicle of human campylobacteriosis needs to be examined further in respect to
      other factors such as dose-response information, consumption data, frequency of
      undercooking and cross contamination.

PMID- 15718034
TI  - Letter to the editor of the international journal of food microbiology.

PMID- 15718035
TI  - Mean age of onset in familial Alzheimer's disease is determined by amyloid beta
      42.
AB  - More than 130 known mutations in the presenilin-1 (PS1) gene result in familial
      Alzheimer's disease (FAD) with a mutation specific age of disease onset. These
      mutations increase amyloid beta 42 (A beta42) levels, and this increase has been
      validated in recent years as one pathogenic factor in FAD. However, further
      malfunctions of mutant presenilin-1 are discussed as well. In order to assess the
      weight of A beta42 regarding the pathogenesis of FAD, we expressed mutant forms
      of PS1 (30-65 years onset age) in COS-7 cells and analyzed amyloid beta levels by
      a novel ELISA. We found a strong correlation (r = 0.98; p<0.001) between the A
      beta40/42-ratio and mean age of disease onset indicating a substantial extent of
      A beta42 contribution to FAD pathology. Our data strongly suggest that A beta42
      is the decisive factor for age of onset in FAD.

PMID- 15718036
TI  - Influence of the Glu298Asp polymorphism of NOS3 on age at onset and homocysteine
      levels in AD patients.
AB  - The distribution of the Glu298Asp polymorphism in NOS3 gene was determined in 405
      Italian patients with "probable" Alzheimer's disease (AD) compared with 253 age
      matched controls. Total plasma homocysteine (tHcy) levels were evaluated in 97
      patients and 23 controls, and were correlated with the Glu298Asp genotype. A
      significantly increased frequency of the Glu/Glu genotype in late onset AD (LOAD)
      patients was found. tHcy levels were significantly increased in patients compared
      with controls and, notably, higher in LOAD than in early onset AD (EOAD).
      Stratifying by the Glu298Asp genotype, a trend toward an increase of tHcy was
      present in Glu/Glu homozygous. This wild type genotype seems to be associated
      with LOAD. tHcy levels are significantly increased in AD compared with controls
      and, moreover, higher in LOAD than in EOAD, possibly in correlation with the
      microvascular disease occurring with aging. Besides, a contribution of the
      Glu/Glu genotype in increasing tHcy levels has been observed.

PMID- 15718037
TI  - Sequence variants of IDE are associated with the extent of beta-amyloid
      deposition in the Alzheimer's disease brain.
AB  - Insulin degrading enzyme, encoded by IDE, plays a primary role in the degradation
      of amyloid beta-protein (A beta), the deposition of which in senile plaques is
      one of the defining hallmarks of Alzheimer's disease (AD). We recently identified
      haplotypes in a broad linkage disequilibrium (LD) block encompassing IDE that
      associate with several AD-related quantitative traits. Here, by examining 32
      polymorphic markers extending across IDE and testing quantitative measures of
      plaque density and cognitive function in three independent Swedish AD samples, we
      have refined the probable position of pathogenic sequences to a 3' region of IDE,
      with local maximum effects in the proximity of marker rs1887922. To replicate
      these findings, a subset of variants were examined against measures of brain A
      beta load in an independent English AD sample, whereby maximum effects were again
      observed for rs1887922. For both Swedish and English autopsy materials, variation
      at rs1887922 explained approximately 10% of the total variance in the respective
      histopathology traits. However, across all clinical materials studied to date,
      this variant site does not appear to associate directly with disease, suggesting
      that IDE may affect AD severity rather than risk. Results indicate that alleles
      of IDE contribute to variability in A beta deposition in the AD brain and suggest
      that this relationship may have relevance for the degree of cognitive dysfunction
      in AD patients.

PMID- 15718038
TI  - Regulation of Hfe by stress factors in BV-2 cells.
AB  - Mutations in the Hfe gene can be associated with the iron overload disorder known
      as hemochromatosis. A number of recent studies suggest that carrying an Hfe
      mutation is a risk factor or genetic modifier for Alzheimer's disease (AD). In
      AD, Hfe protein expression is induced on cells associated with neuritic plaques
      and on neurons in the periplaque area. In this study, the factors that may be
      responsible for induction of Hfe in AD brain were determined using BV-2 cells.
      Hfe expression was induced by serum deprivation, menadione and beta-amyloid. The
      labile iron pool was consistently decreased when Hfe expression increased.
      However, the changes in expression of Hfe appeared independent of the expression
      of transferrin receptor and ferritin. These data provide insight into the
      induction of Hfe in AD and indicate that Hfe expression may be a protective
      function to limit cellular iron exposure during cell stress. These results are
      the first in a series of studies to understand how mutations in Hfe can be a risk
      factor for AD.

PMID- 15718039
TI  - Quantification of apolipoprotein E receptors in human brain-derived cell lines by
      real-time polymerase chain reaction.
AB  - Apolipoprotein (apo) E4 is a risk factor for Alzheimer's disease (AD) and other
      neurodegenerative diseases, compared to wild-type apoE3. The mechanism(s) is
      unknown. One possibility, demonstrated in peripheral tissue cell lines, is that
      apoE stimulates nitric oxide synthase (NOS) via a receptor-dependent signalling
      pathway and that apoE4 generates inappropriate amounts of nitric oxide (NO)
      compared to apoE3. Prior to biochemical investigations, we have quantified the
      expression of several candidate receptor genes, including low-density lipoprotein
      receptor (LDL-r) family members and scavenger receptor class B, types I and II
      (SR-BI/II), as well as the three NOS isoenzymes and protein kinase B (Akt), in 38
      human cell lines, of which 12 derive from brain. Expression of apoE receptor 2
      (apoER2), a known signalling receptor in brain, was readily detected in SH-SY-5Y
      and CCF-STTG1 cells, common models of neurons and astrocytes, respectively, and
      was highest in H4 neuroglioma, NT-2 precursor cells and IMR-32 neuroblastoma
      cells. Transcripts of the other lipoprotein receptors were widely, but variably,
      distributed across the different cell types. Of particular note was the
      predominant expression of SR-BII over SR-BI in many of the brain-derived cells.
      As the C-terminus of SR-BII, like apoER2, contains potential SH3 signalling
      motifs, we suggest that in brain SR-BII functions as a signal transducer
      receptor.

PMID- 15718040
TI  - Fibroblast glutamate transport in aging and in AD: correlations with disease
      severity.
AB  - Altered glutamate transport and aberrant EAAT1 expression were shown in
      Alzheimer's disease (AD) brains. It is presently unknown whether these
      modifications are a consequence of neurodegeneration or play a pathogenetic role.
      However, recent findings of decreased glutamate uptake, EAAT1 protein and mRNA in
      AD platelets suggest that glutamate transporter modifications may be systemic and
      might explain the decreased glutamate uptake. We now used primary fibroblast
      cultures from 10 AD patients to further investigate the specific involvement of
      glutamate transporters in this disorder and in normal aging. Decreased glutamate
      uptake (p<0.001), EAAT1 expression (p<0.05) and mRNA (p<0.01) were observed in
      aged people, compared to younger controls. In AD fibroblasts, compared to age
      matched controls, we observed further reductions of glutamate uptake (p<0.0005)
      and EAAT1 expression (p<0.005), while EAAT1 mRNA increase (p<0.001) was shown.
      EAAT1 parameters were mutually correlated (p<0.01) and correlations were shown
      with dementia severity (p<0.05 MMSE-expression, p<0.005 MMSE-mRNA). We suggest
      fibroblast cultures as possible ex vivo peripheral model to study the glutamate
      involvement and possible molecular and therapeutic targets in AD.

PMID- 15718041
TI  - Enhanced GM1 ganglioside catabolism in cultured fibroblasts from Alzheimer
      patients.
AB  - The metabolic processing of GM1 ganglioside, exogenously administered to cultured
      skin fibroblasts, was investigated on cells obtained from patients affected with
      Alzheimer disease, in comparison with age-matched control subjects. Cultured
      fibroblasts were incubated with GM1 ganglioside, [(3)H]-radiolabelled at the
      sphingosine moiety. It was observed that the extent of tritiated GM2 and GM3
      ganglioside formation was higher in AD fibroblasts than in control cells. The
      activity of acidic beta-D-galactosidase, responsible of GM1 hydrolysis to GM2
      within lysosomes, assayed in vitro on cell lysates, was increased in AD
      fibroblasts in comparison with control cells. These data suggest that up
      regulation of lysosomal enzymes could be responsible of the enhanced GM1
      catabolism in AD fibroblasts. Finally, it was found that the extent of GM1
      hydrolysis in AD fibroblasts was inversely correlated with the mini-mental score
      index of patients. The increased hydrolysis rate of sphingolipids could be taken
      as peripheral hallmark of Alzheimer's disease patients.

PMID- 15718042
TI  - Mitochondrial function in fibroblasts with aging in culture and/or Alzheimer's
      disease.
AB  - Mitochondrial membrane potentials (MMP) reflect the functional state of the
      mitochondria within cells. Our recently published method provides a quantitative
      estimate of the MMP of populations of mitochondrial-like particles (MLP) within
      living cells at 37 degrees C using the combination of conventional fluorescence
      microscopy, 3D-deconvolution and exhaustive photon reassignment (EPR). Although
      the method does not provide an absolute measure of MMP, these relative MMP allow
      direct comparison between various mitochondria in cells at various ages in
      culture and in different cell lines from multiple patients. Fibroblasts lines
      from four Alzheimer's disease (AD) patients bearing the presenilin-1 (PS-1)
      mutation and four appropriate controls were evaluated at different ages in
      culture. The results showed a large variation in the relative MMP, cell size and
      sum of relative MMP of all MLP within each cell or within each cell line.
      Nevertheless, combining the values of relative MMP for the cell lines in each
      group revealed changes in distribution with age in culture. The relative MMP
      decreased while the cell sizes and sum of relative MMP within each cell increased
      with age in fibroblasts. Values did not differ between controls and the AD
      patients bearing PS-1 mutation at any age in cultures. This new, sensitive and
      quantitative estimate of relative MMP indicates that under non-stressed
      conditions relative MMP change with aging in culture, but relative MMP do not
      differ between controls and AD subjects.

PMID- 15718044
TI  - Oxidative state in platelets and erythrocytes in aging and Alzheimer's disease.
AB  - Several studies have shown involvement of peroxynitrite anion, a potent oxidative
      agent, in Alzheimer's disease (AD) neuropathology. Herein, we assessed in
      platelets and erythrocytes of AD patients, age-matched and young adults controls:
      thiobarbituric acid-reactive substances (TBARS) production; superoxide dismutase
      (SOD), nitric oxide synthase (NOS) and Na,K-ATPase activities; cyclic GMP (cGMP)
      content, both basal and after sodium nitroprusside (SNP) stimulation. Aging was
      associated with an increase in TBARS production and NOS activity, a decrease in
      basal cGMP content and no change in SOD and Na,K-ATPase activities. AD patients,
      compared to aged controls, have: increase in TBARS production and in NOS, SOD and
      Na,K-ATPase activities but no alteration in basal cGMP content. SNP increased
      cGMP platelets production in all groups. In conclusion, we demonstrated in
      platelets and erythrocytes a disruption in systemic modulation of oxidative
      stress in aging and with more intensity in AD.

PMID- 15718043
TI  - Inhibition of Alzheimer's amyloid-beta peptide-induced reduction of mitochondrial
      membrane potential and neurotoxicity by gelsolin.
AB  - Amyloid-beta (A beta) peptides play a central role in the development of
      Alzheimer's disease. They are known to induce mitochondrial dysfunction and
      caspase activation, resulting in apoptosis of neuronal cells. Here we show that
      human cytoplasmic gelsolin inhibits A beta peptide-induced cell death of
      neuronally differentiated rat pheochromocytoma (PC-12) cells. We also show that
      the segment 5 but not 6 of human cytoplasmic gelsolin is the important region
      responsible for inhibition of A beta-induced cytotoxicity. Mitochondrial
      dysfunction associated with cell death, membrane potential loss and the release
      of cytochrome c are all abrogated in the presence of human full-length or segment
      5 cytoplasmic gelsolin. Furthermore, RNA interference to reduce expression of
      endogenous gelsolin in PC-12 cells shows that rat gelsolin act as an inhibitor of
      A beta cytotoxicity. These results demonstrate that cytoplasmic gelsolin plays a
      important role in inhibiting Abeta-induced cytotoxicity by inhibiting apoptotic
      mitochondrial changes. The segment 5 of human cytoplasmic gelsolin is sufficient
      for the function.

PMID- 15718045
TI  - Small hippocampal size in cognitively normal subjects with coronary artery
      disease.
AB  - OBJECTIVE: Hippocampal size reduction detected by three-dimensional structural
      magnetic resonance imaging (3D-MRI) represents an important hallmark of
      Alzheimer's disease (AD). Recently, epidemiological and neuropathological studies
      have associated coronary artery disease (CAD) and cardiovascular risk factors
      with AD. The present study aimed to assess whether small hippocampal size is also
      a feature of CAD. METHODS: Hippocampal volumes were assessed in 20 men with CAD
      and 20 healthy matched control subjects by use of 3D-MRI. Subjects with a history
      of neurological or psychiatric disorder, or signs of cognitive impairment were
      rigorously excluded. RESULTS: Compared with controls, subjects with CAD had
      significantly smaller (-14%) hippocampal volumes. Cardiovascular risk factors
      were not related to hippocampal volumes of CAD subjects. CONCLUSIONS: Our results
      demonstrate small hippocampal size in CAD subjects without any cognitive
      impairment. Future studies should clarify whether the annual rate of hippocampal
      volume loss of persons with CAD is greater than that of healthy individuals and
      predicts later cognitive decline or dementia.

PMID- 15718046
TI  - 1H MRS in stroke patients with and without cognitive impairment.
AB  - The pathophysiological basis of cognitive impairment in patients with
      cerebrovascular disease (CVD) is not well understood, particularly in relation to
      the role of non-infarction ischemic change and associated Alzheimer-type
      pathology. We used single voxel 1H MRS to determine the differences in brain
      neurometabolites in non-infarcted frontal white matter and occipito-parietal gray
      matter of 48 stroke patients with or without cognitive impairment and 60 elderly
      controls. The results showed that there were no significant neurometabolite
      differences between the stroke cohort and healthy elderly controls, but there was
      a difference in NAA/H2O between the stroke patients that had cognitive impairment
      (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with
      those patients with no impairment. This was significant in the occipito-parietal
      gray matter, but not in the frontal white matter, although the results were in
      the same direction for the latter. This suggests that cognitive impairment in
      stroke patients may be related to cortical neuronal dysfunction rather than
      purely subcortical change. Moreover, cortical regions not obviously infarcted may
      have dysfunctional neurons, the pathophysiological basis for which needs further
      study.

PMID- 15718047
TI  - Memories that last in old age: motor skill learning and memory preservation.
AB  - Using an automated test panel, age-associated declines in learning, remembering
      and performing a novel visuomotor task were assessed in 497 normal adults ranging
      from 18 to 95 years old. As predicted, task performance times slowed with
      increasing age in the cross-sectional portion of the study. However in the
      subsequent longitudinal study, while motor learning was significantly slower in
      adults over 62 years old, motor memory was pristinely preserved in normal adults
      from 18 to 95 years old. When tested 2 years after the first training session and
      without intervening rehearsal, mean performance times were retained and continued
      to improve by 10% in young adults and 13% in aged adults, reflecting long lasting
      preservation of motor memories. While the maximum lifetime of an unpracticed,
      novel motor memory in humans is not known, the present study suggests that new
      motor memories can be retained for at least 2 years without rehearsal in normal
      aged adults. This age-resistant component of motor memory stands in contrast to
      the well-known decrements in other motor and cognitive processes with human
      aging.

PMID- 15718048
TI  - Cortical 6-[18F]fluoro-L-dopa uptake and frontal cognitive functions in early
      Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) have already at the early stages of the
      disease impaired performance especially in tests measuring frontal lobe functions
      such as attention. The pathophysiological basis of these deficits is unclear. In
      the present study, 21 non-demented, non-medicated patients at the early stage of
      PD and 24 healthy controls underwent a positron emission tomography (PET) scan
      with 6-[18F]fluoro-L-dopa (Fdopa) as the tracer. In addition, the PD patients
      performed a neuropsychological test battery, including a test measuring sustained
      attention (VIG) and a test requiring suppressed attention (Stroop). Both voxel
      based Statistical Parametric Mapping (SPM) and automated region of interest (ROI)
      analysis were employed. Compared to controls, the PD patients had decreased Fdopa
      uptake in the striatum and a large cortical area of increased Fdopa uptake. The
      reaction time in the VIG test correlated positively with the Fdopa uptake of the
      dorsolateral prefrontal cortex and the performance in the Stroop test correlated
      negatively with the Fdopa uptake in an area including the medial frontal cortex
      and the anterior cingulate. The results show that cortical Fdopa uptake is
      increased in early non-medicated PD and suggest that the changes in frontal Fdopa
      uptake are related to cognitive impairments found in early PD.

PMID- 15718049
TI  - The effects of aging and oxidative stress on learning behavior in C. elegans.
AB  - Oxidative stress is associated with age-related declines of biological functions.
      However, the nervous system is preserved during aging in Caenorhabditis elegans
      and, thus, it is not well explored whether aging and oxidative stress affect
      nervous functions. Here we report that age-related decline can be observed in a
      type of associative-learning behavior, referred to as isothermal tracking. We
      also report the effects of mutants with altered sensitivity to oxidative stress
      on learning behavior and motor activity in young adults. The isp-1 and clk-1
      mutants are members of the Clk class of mutants and have deficits in the function
      of the mitochondrial respiratory chain, leading to reduced levels of oxidative
      stress, increased longevity, delayed rhythmic behaviors and other phenotypes.
      Both the Clk mutations and pretreatment with a metabolic antioxidant, alpha
      lipoic acid (LA), increased the ability to show isothermal tracking and modestly
      reduced motor activity. Mutants with increased oxidative stress showed severely
      impaired learning behavior and modestly reduced motor activity. Therefore,
      physiological levels of oxidative stress may be too high for learning behavior
      but, perhaps, not for motor activity. We discuss the relevance of oxidative
      stress to the aging and evolution of behaviors.

PMID- 15718050
TI  - Age-related changes in cyclic GMP and PKG-stimulated cerebellar Na,K-ATPase
      activity.
AB  - Energy deficiency and dysfunction of the Na,K-ATPase are common consequences of
      many pathological insults. Glutamate through cyclic GMP and cyclic GMP-dependent
      protein kinase (PKG) has been shown to stimulate alpha(2/3)-Na,K-ATPase activity
      in the central nervous system. Thus, a slight impairment of this pathway may
      amplify the disruption of ion homeostasis in the presence of a non-lethal insult.
      We investigate the effect of aging (4, 12 and 24 months) on the glutamate-cyclic
      GMP-PKG modulation of alpha1, alpha(2/3)-Na,K-ATPase activity in rat cerebellum
      and the stimulation of the glutamate-cyclic GMP-PKG pathway at different levels.
      Cyclic GMP levels and alpha(2/3)-Na,K-ATPase activity were progressively
      decreased from 4 and 24 month-old animals. However, PKG basal activity was
      reduced between 4 and 12 months, and no additional change was observed at 24
      months. The ability of 8-Br-cyclic GMP to stimulate PKG activity was only reduced
      between 12 and 24 months. Moreover, glutamate or 8-Br-cyclic GMP promoted a
      smaller increase of alpha(2/3)-Na,K-ATPase activity at 24 months, when compared
      to 4 and 12 months. In spite of the age-related reduced basal levels of cyclic
      GMP, the production induced by CO or NO was not age-related. Finally, inhibition
      of PKG activation by KT5823 revealed a lower sensitivity of the enzyme at the
      older age. Taken together, these data show that basal age-related decline in
      sodium pump activity is a consequence of changes in different steps of the cyclic
      GMP-PKG pathway. On the other hand, age-related reduction in glutamate positive
      modulation of cerebellar alpha(2/3)-Na,K-ATPase is linked to a defective PKG
      signaling pathway.

PMID- 15718051
TI  - Aging affects choroidal proteins involved in CSF production in Sprague-Dawley
      rats.
AB  - Aging is currently associated with progressive declines of cerebral functions.
      From these, a decreased resistance to dehydration suggested alteration in
      choroidal control of brain homeostasis and reduced cerebrospinal fluid (CSF)
      production in old subjects. In the present study, choroid plexuses of 20-month
      old Sprague-Dawley rats were compared with those of 3- and 10-month old rats.
      Using ultrastructure analysis and immunodetection of ezrin, a protein associating
      cytoskeleton to membranes, we showed that progressive loss of microvilli and
      strong decrease in apical ezrin are evident in 20-month old rats. Using
      immunolabeling and confocal microscopy, we found reduction in expression of two
      choroidal proteins, carbonic anhydrase II and aquaporin 1, involved in CSF
      secretion. In addition, we confirmed previous studies indicating that choroidal
      Na,K-ATPase decreased with age. In situ hybridization analyses showed that mRNA
      levels for Na,K-ATPase and aquaporin 1 were significantly lowered in choroid
      plexus of old rats. These findings are consistent with a reduced secretory
      activity in choroid plexus and suggest that massive disorders could affect
      choroidal CSF production in aged rats.

PMID- 15718052
TI  - Local expression of GH and IGF-1 in the hippocampus of GH-deficient long-lived
      mice.
AB  - Beneficial effects of growth hormone (GH) and insulin-like growth factor-1 (IGF
      1) on the development and function of the central nervous system are well
      documented. In spite of primary deficiency of GH and secondary IGF-1 deficiency,
      Ames dwarf mice live considerably longer than normal animals, exhibit apparently
      normal cognitive functions and maintain them into advanced age. In an attempt to
      reconcile these findings, we have examined local expression of GH and IGF-1 in
      the hippocampus of normal and Ames dwarf mice. We found that both hippocampal GH
      and IGF-1 protein levels are increased and the corresponding mRNAs are normal in
      Ames dwarf as compared with normal mice. Increased phosphorylation of Akt and
      cyclic AMP responsive element-binding protein (CREB) were detected in the
      hippocampus of Ames dwarf mice. Our results suggest that increase in hippocampal
      GH and IGF-1 protein expression and subsequent activation of PI3K/Akt-CREB signal
      transduction cascade might contribute to the maintenance of cognitive function
      and is likely to be responsible for the integrity of neuronal structure, and
      maintenance of youthful levels of cognitive function in these long-lived mice
      during aging.

PMID- 15718053
TI  - Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning.
AB  - Hippocampus-mediated learning enhances neurogenesis in the adult dentate gyrus
      (DG), and this process has been suggested to be involved in memory formation. The
      hippocampus receives abundant cholinergic innervation and acetylcholine (ACh)
      plays an important role in learning and Alzheimer's disease (AD) pathophysiology.
      Here, we show that a selective neurotoxic lesion of forebrain cholinergic input
      with 192 IgG-saporin reduces DG neurogenesis with a concurrent impairment in
      spatial memory. Conversely, systemic administration of the cholinergic agonist
      physostigmine increases DG neurogenesis. We find that changes of forebrain ACh
      levels primarily influence the proliferation and/or the short-term survival
      rather than the long-term survival or differentiation of the new neurons. We
      further demonstrate that these newly born cells express the muscarinic receptor
      subtypes M1 and M4. Our data provide evidence that forebrain ACh promotes
      neurogenesis, and suggest that the impaired cholinergic function in AD may in
      part contribute to deficits in learning and memory through reductions in the
      formation of new hippocampal neurons.

PMID- 15718054
TI  - The anesthetics nitrous oxide and ketamine are more neurotoxic to old than to
      young rat brain.
AB  - Nitrous oxide (N2O) and ketamine are common general anesthetics and antagonists
      of N-methyl-D-aspartate (NMDA) glutamate receptors. In clinically relevant
      concentrations, they induce a psychotomimetic reaction in humans and
      pathomorphological changes in the rat brain. We have previously shown that
      ketamine and N2O in combination cause the neurotoxic reaction in young adult rat
      brain that is apparently synergistic. Ketamine and N2O are occasionally used in
      geriatric anesthesia since they do not suppress cardiorespiratory function and
      thus are beneficial for frail elderly patients. However, in view of the evidence
      that N2O and ketamine have potentially serious neurotoxic effects, and that they
      potentiate one another's neurotoxicity, their neurotoxic potential in the aging
      brain needs to be evaluated. In this study we compared the neurotoxicity of
      ketamine and N2O, alone or in combination, in aging (18- and 24-month-old) rats
      and in young adult (6-month-old) rats and found that the aging brain is
      substantially more sensitive than the young adult brain to the neurotoxic
      reaction induced by either ketamine alone or the ketamine + N2O combination, but
      equally sensitive to the neurotoxicity induced by N2O alone.

PMID- 15718055
TI  - Caffeine reverses age-related deficits in olfactory discrimination and social
      recognition memory in rats. Involvement of adenosine A1 and A2A receptors.
AB  - Caffeine, a non-selective adenosine receptor antagonist, has been suggested as a
      potential drug to counteract age-related cognitive decline since critical changes
      in adenosinergic neurotransmission occur with aging. In the present study,
      olfactory discrimination and short-term social memory of 3, 6, 12 and 18 month
      old rats were assessed with the olfactory discrimination and social recognition
      tasks, respectively. The actions of caffeine (3.0, 10.0 and 30.0 mg/kg, i.p.),
      the A1 receptor antagonist DPCPX (1.0 and 3.0 mg/kg, i.p.) and the A2A receptor
      antagonist ZM241385 (0.5 and 1.0 mg/kg, i.p.) in relation to age-related effects
      on olfactory functions were also studied. The 12 and 18 month-old rats exhibited
      significantly impaired performance in both models, demonstrating deficits in
      their odor discrimination and in their ability to recognize a juvenile rat after
      a short period of time. Acute treatment with caffeine or ZM241385, but not with
      DPCPX, reversed these age-related olfactory deficits. The present results suggest
      the participation of adenosine receptors in the control of olfactory functions
      and confirm the potential of caffeine for the treatment of aged-related cognitive
      decline.

PMID- 15718056
TI  - Changes in glutamate receptor function in synaptic input to the superficial
      superior colliculus (SSC) with aging and in retinal degeneration in the Royal
      College of Surgeons (RCS) rat.
AB  - Ionotropic and metabotropic glutamate receptors mediate and modulate
      retinocollicular transmission. The Royal College of Surgeons (RCS) dystrophic
      strain of rats suffers from a progressive retinal degeneration with age and hence
      loss of visual function. We investigated whether this loss of function is
      accompanied by functional changes in a central target of retinal axons, the
      superficial superior colliculus (SSC). Field potential recordings were made in
      SSC slices from RCS rats aged either 4-7 weeks or 33-52 weeks. Blockade of
      GABAergic transmission revealed a field EPSP in response to optic tract
      stimulation which was sensitive to the NMDA antagonist AP5. In normal non
      dystrophic rats the contribution of NMDA receptors to the fEPSP declined with
      age, whereas in dystrophic animals no such decline was seen. As mGluR8 may be
      located on terminals of retinal axons, we also assessed the function of this
      receptor. The mGluR8 agonist DCPG reduced fEPSPs in normal and dystrophic rats in
      both age groups to a similar extent, although the effect of DCPG declined with
      age. These findings indicate that the contribution of NMDA receptors to
      retinocollicular transmission declines with age in normal rats, but that such a
      decline is not seen in dystrophic rats which have severely reduced visual
      function. As NMDA receptors are associated with neural plasticity, it may be that
      this finding represents an increased residual potential for plasticity in
      dystrophic rats which may be functionally important.

PMID- 15718057
TI  - Mouse strain-specific changes in nicotinic receptor expression with age.
AB  - The onset and severity of age-related loss of neuronal nicotinic acetylcholine
      receptor (nAChR) expression in the mammalian hippocampus can vary considerably
      between individuals. We have examined the expression of four nAChR subunits
      (nAChR alpha4, nAChR alpha5, nAChR alpha7 and nAChR beta4) in the dorsal
      hippocampus of adult (12-14 months) and aged (24-28 month) animals from two-mouse
      strains (CBA/J and C57BL/6). The expression of nAChR alpha4 was selectively
      diminished with age in both strains, and there was a significant loss of nAChR
      alpha7 in CA1 of aged CBA/J, but not C57BL/6. There was no change in nAChR alpha5
      expression with age whereas nAChR beta4 preferentially diminished in the C57BL/6
      CA1 region and remained the same or slightly increased in the aged CBA/J.
      Coincident with the loss of neuronal nAChR alpha4 in the CBA/J strain was a
      significant age-related increase of nAChR alpha4 staining of astrocytes, most
      notably in the stratum radiatum. These results suggest that mouse strains of
      different genetic backgrounds undergo dissimilar age-related changes in the
      expression of nAChRs.

PMID- 15718058
TI  - Measuring alcohol consumption: a comparison of graduated frequency, quantity
      frequency, and weekly recall diary methods in a general population survey.
AB  - OBJECTIVE: The objective of this study is to compare self-reports of alcohol
      consumption obtained by graduated frequency (GF), quantity frequency (QF), and
      prospective weekly diary methods in a Swiss general population survey using a
      within-subject design. Another objective is to examine the consumption means,
      ranking order, and drinking classifications and to relate differences in
      consumption means and classification inconsistencies to social and drinking
      characteristics. METHOD: The data came from the first wave of a longitudinal
      study on changes in alcohol consumption. A subsample of 767 respondents who
      completed the three measures was examined. The sample design was accounted for.
      RESULTS: Weekly drinking diary (WDD) yielded over 50% more alcohol consumption
      than the QF and GF measures did. Measures on quantity and graduated frequencies
      did not differ significantly. There were more light drinkers found on QF and more
      harmful drinkers on the WDD. Classification inconsistencies between GF and the
      weekly drinking diary were significantly related to gender and problematic
      drinking.

PMID- 15718059
TI  - The impact of contracting and prompting substance abuse treatment entry: a pilot
      trial.
AB  - Contracting and prompting clients to attend substance abuse treatment aftercare
      substantially improves treatment adherence and outcome. However, this approach
      has not been evaluated for improving entry into initial treatment. We recruited
      102 individuals scheduled to begin a 28-day substance use disorder (SUD)
      residential treatment program and randomly assigned them to receive either our
      standard treatment (STX) or STX plus attendance contracting and prompting (CP).
      CP participants showed fewer subsequent hospitalization days, lower
      hospitalization costs, greater improvement in alcohol problem scores, and lower
      legal problem scores at a 3-month follow-up than the STX group. The two groups
      did not differ on treatment entry rate, time in treatment, or drug use problem
      scores. The clinical utility of CP procedures and areas for future research are
      discussed.

PMID- 15718061
TI  - Differences in accuracy of offspring assessment based on parental smoking status.
AB  - To investigate the accuracy of offspring assessments of parental smoking status,
      we studied 116 parents and 151 adult children (276 parent-child dyads) who
      provided data on both their own and their parents' smoking status. All currently
      smoking and all ex-smoking parents were correctly classified as ever-smokers by
      their offspring (n = 79 and 100, respectively). Of the 97 offspring who reported
      on never-smoking parents, 88 correctly classified their parents as never-smokers.
      Thus, sensitivity for detecting ever-smoking in parents was 100%, and
      specificity, 91%. Because all incorrect classifications involved never-smoking
      parents, further analyses focused on this group. Too few parents were
      misclassified to permit testing of parental characteristics. Offspring who
      misclassified their parents were significantly older than those who did not;
      neither sex nor smoking status of the offspring was associated with the increased
      likelihood of misclassification. No significant differences were discovered for
      dyadic factors (concordance/discordance for sex; parent-offspring age
      difference). Overall, these results support the utility of proxy reports of
      parental smoking phenotype by adult informants when self-report is unavailable.

PMID- 15718060
TI  - Perceived risks and benefits of smoking cessation: gender-specific predictors of
      motivation and treatment outcome.
AB  - The primary aim of this study was to examine gender differences in perceived
      risks and benefits of smoking cessation and their relationship to pretreatment
      motivation and treatment outcome. No validated measures that comprehensively
      assess perceived risks and benefits associated with smoking cessation were
      available in the literature; consequently, we developed a self-report instrument
      [Perceived Risks and Benefits Questionnaire (PRBQ)] for this purpose. A sample of
      573 treatment-seeking smokers (48% female) entering smoking cessation trials
      completed the PRBQ, and its association with treatment outcome was assessed in a
      subsample of 93 participants. Overall, the PRBQ demonstrated good psychometric
      properties. Females indicated greater likelihood ratings of perceived risks and
      benefits than males. For women and men, perceived benefits were positively
      associated with motivation, and perceived risks were negatively associated with
      motivation and treatment outcome. Women evidenced stronger associations between
      perceived risks and pretreatment motivation, and treatment outcome. Knowledge of
      perceived risks and benefits associated with smoking cessation is critical for
      public education campaigns and could inform intervention strategies designed to
      modify sex-specific beliefs associated with lowered behavioral intentions to quit
      smoking.

PMID- 15718062
TI  - Short-term outcomes of five heroin detoxification methods in the Australian NEPOD
      Project.
AB  - This study included 380 participants in five heroin detoxification trials whose
      data were pooled to enable direct comparison of five detoxification methods in
      the Australian National Evaluation of Pharmacotherapies for Opioid Dependence
      (NEPOD). Rapid detoxification achieved similar initial abstinence rates with
      either anaesthesia or sedation (average 59%), which were higher than was achieved
      by inpatient detoxification using clonidine plus other symptomatic medications
      (24%), which in turn was higher than outpatient detoxification using either
      buprenorphine (12%) or clonidine plus other symptomatic medications (4%). Older
      participants and those using more illicit drugs were more likely to achieve
      abstinence. Entry rates into ongoing postdetoxification treatment were as
      follows: buprenorphine outpatient (65%), sedation (63%), anaesthesia (42%),
      symptomatic outpatient (27%), and symptomatic inpatient (12%). Postdetoxification
      treatment with buprenorphine or methadone was preferred over naltrexone.
      Participants with more previous detoxification attempts were more likely to enter
      postdetoxification treatment. Given that outpatient detoxification was more
      effective with buprenorphine than with symptomatic medications and that rapid
      detoxification was more effective than the symptomatic inpatient method, the
      roles of the symptomatic methods should be reconsidered.

PMID- 15718063
TI  - Effect of working status on tobacco, alcohol, and drug use among adolescents in
      urban area of Thailand.
AB  - To examine the relationship between working status and behavior of substance use
      such as tobacco, alcohol, and drug among adolescents, a survey of 215 students in
      the seventh to ninth grades was conducted in urban area of Thailand. The sample
      consisted of 100 workers (46.5%) and 115 nonworkers (53.5%). The percentages of
      participants with some experiences of smoking, drinking alcohol, and drug use
      were 17.2%, 48.8%, and 3.3%, respectively. The participants with experiences of
      smoking and drinking alcohol in the working group were significantly higher than
      in the nonworking group (P<0.001), while the relationship between working status
      and drug use was weaker than the other relationships between working status and
      tobacco or alcohol use. The backward logistic regression analysis was refined
      until it included three independent variables: tobacco use, alcohol use, and
      household income. On the other hand, it was found that working condition,
      including working hours and working at night, had little impact on smoking,
      drinking alcohol, and drug use. However, the type of job was significantly
      related to tobacco use (P<0.05) by binary analysis and multiple regression
      analysis. These findings suggest that employment of young adolescents in urban
      area of Thailand has an influence on smoking and drinking alcohol. Especially,
      working status probably affect smoking behavior among young adolescents in the
      urban area of Thailand.

PMID- 15718065
TI  - Does personality mediate the relation between alcohol consumption and
      cardiovascular disease morbidity and mortality?
AB  - Alcohol volume and pattern have been previously demonstrated to predict
      cardiovascular disease (CVD) in these data. The objective of this study is to
      assess whether personality is a mediator in this relationship. Interview data
      from 1154 men and women aged 18-64 in Winnipeg, Canada were linked to health care
      utilization and mortality records, with 8 years of follow-up. Cox regressions
      were performed for men and women on time to first event for physician visits,
      hospitalizations, and deaths due to coronary heart disease (CHD), hypertension,
      or other CVD. Models linking drinking to CHD outcomes were unaffected by
      personality covariates. Models of hypertension and other CVD outcomes were
      significantly affected by inclusion of personality covariates, but the only
      significant individual personality covariate was in the effect on other CVD in
      men: Ego strength had a protective effect [hazard ratio (HR)=0.95]. Personality
      covariates as measured by the Eysenck Personality Questionnaire (EPQ) and
      Barron's Ego Strength Scale make only a modest contribution to statistical models
      of the relation between drinking and cardiovascular health.

PMID- 15718064
TI  - A pilot study of an alcoholic liver disease recurrence prevention education
      program in hospitalized patients with advanced liver disease.
AB  - No systematic work has been completed to assess whether or not educational
      programming might exert lifestyle improvements among alcoholic liver disease
      (ALD) inpatients. The present pilot study sought to answer this question through
      the use of a small-scale two-group experiment (five-session education program
      versus standard care) at a state-of-the art Liver Unit that provided tertiary
      care of indigent patients with advanced ALD. A total of 44 patients were
      initially randomly assigned to program conditions, and 25 provided 3-month follow
      up data (13 in the program condition, 12 in the control condition). Patients who
      received the program reported high receptivity to it, and showed greater learning
      of program material and reported greater lifestyle changes than the control
      patients. For those ALD inpatients that are able and willing to participate, the
      program shows promising effects on self-reported lifestyle change.

PMID- 15718066
TI  - The unique relationship between fear of cognitive dyscontrol and self-reports of
      problematic drinking.
AB  - Research has established positive associations between anxiety sensitivity (AS)
      and problematic drinking in clinical samples. The present study confirmed this
      relationship in a nonclinical sample (N=162) and investigated which AS dimension
      best predicts self-reports of problematic drinking. Only one AS facet, fear of
      cognitive dyscontrol (FCC), was associated with symptoms of alcohol dependence,
      severity of drinking problems, and alcohol-related expectations of global,
      positive changes, sexual enhancement, and tension reduction. The possible role of
      depression in these relationships was also evaluated. A series of hierarchical
      regressions revealed that, when trait anxiety, anxious arousal, and anxious
      apprehension were statistically removed, depression did not contribute
      significant variance beyond the effects of FMC and other anxiety measures.
      Results suggest that FCC is uniquely associated with self-reports of problematic
      drinking behaviors and attitudes. Implications for tension-reduction models of
      alcohol are discussed.

PMID- 15718067
TI  - Development of a multidimensional measure of tobacco dependence in adolescence.
AB  - The objective of this research was to develop a multidimensional measure of
      tobacco dependence, sensitive to signs of incipient dependence and relevant to
      adolescents. A cross-sectional survey was conducted of students attending
      randomly selected high schools in two regions of British Columbia, Canada. Of the
      3280 adolescents who completed the survey, 17% (n=562) indicated that they had
      smoked at least once in the month preceding the survey and were classified as
      "smokers." Ninety-one percent of the smokers (n=513) completed all or most of the
      items and comprised the sample for the analysis. The survey included a number of
      items related to smoking status and nicotine dependence, including the newly
      developed Dimensions of Tobacco-Dependence Scale (DTDS), a 54-item
      multidimensional measure of tobacco dependence. Exploratory factor analyses using
      MINRES was used to examine the dimensions of the DTDS. The measure was found to
      include four dimensions: social reinforcement, emotional reinforcement, sensory
      reinforcement, and physical reinforcement. All subscales had adequate reliability
      (Cronbach's alpha coefficients >.70).

PMID- 15718068
TI  - Parental occupation, education, and smoking as predictors of offspring tobacco
      use in adulthood: a longitudinal study.
AB  - This study examined the interrelation of parental occupational status (blue-
      versus white-collar), parental education, parental smoking, parent-child
      relations, late adolescent tobacco use, and adult offspring smoking. A
      longitudinal data set was employed, composed of 603 participants who were first
      studied in childhood and then followed to mean age 27 years. Structural Equation
      Modeling (SEM) showed that the distal factors of parental blue-collar status, low
      parental educational achievement, and parental smoking were related to adult
      offspring smoking. Specifically, parental blue-collar status and parental smoking
      were mediated by the latent construct of the parent-child relationship, which in
      turn was mediated by smoking in late adolescence with respect to adult offspring
      smoking. Parental educational level was partially mediated by the parent
      adolescent relationship but also had a direct path to adult offspring smoking.
      The most powerful predictor of offspring smoking in adulthood was smoking in late
      adolescence. Findings imply areas that may be targeted by intervention programs
      to decrease offspring tobacco use.

PMID- 15718069
TI  - Readiness for mental health treatment and for changing alcohol use in patients
      with comorbid psychiatric and alcohol disorders: are they congruent?
AB  - Patients with comorbid psychiatric and alcohol disorders may be ready to change
      one problem but not the other. This study compared 132 dually diagnosed patients'
      readiness for mental health treatment to their readiness to change alcohol use.
      The patients completed a measure of readiness to change alcohol use [the
      University of Rhode Island Change Assessment Scale-Alcohol (URICA-A)] and the new
      Readiness for Mental Health Treatment measure. Confirmatory factor analysis (CFA)
      reveals that the measures have similar factor structures, but correlation and
      cluster analyses suggest that separate levels of patient motivation exist for
      mental health treatment and changing alcohol use. The newly developed mental
      health treatment measure will help clinicians tailor interventions to their
      patients' needs.

PMID- 15718070
TI  - Household survey on drug abuse in Brazil: study involving the 107 major cities of
      the country--2001.
AB  - The prevalence of the use in Brazil of illicit drugs, as well as of alcohol and
      tobacco, was determined. Further, illicit use of psychotropic medicines, and
      anabolic steroids were also surveyed. This study was carried out in 107 Brazilian
      cities with more than 200,000 inhabitants aged 12-65 years. The sampling design
      adopted was that of sampling per aggregates in three stages: first, the census
      sectors were selected; second, homes were selected among the sectors; finally, in
      each home, a respondent was selected in a manner independent of the interviewer.
      There were 8589 persons interviewed. The questionnaire utilized was that of the
      SAMHSA (Substance Abuse and Mental Health Services Administration) which was
      translated and adapted for Brazilian conditions. The lifetime use of alcohol in
      the 107 major cities of the country was 68.7%, which was close to numbers
      observed for Chile at 70.8% and the USA at 81.0%. Yet, tobacco lifetime use was
      41.1% of the total, which is lower than the prevalence observed in the USA
      (70.5%). The data on the lifetime use of marijuana in Brazil (6.9%) approximated
      the findings for Colombia (5.4%), however, being much lower than that observed in
      the USA (34.2%) and the United Kingdom (25.0%). The prevalence of lifetime use of
      cocaine was 2.3%, well below the levels for the USA with 11.2% of the total
      population. The abuse of inhalants was 5.8% of the total, greater than that found
      in Colombia (1.4%) and about four times less than that in the United Kingdom with
      20.0%. Among the medicaments, stimulants had a 1.5% prevalence of lifetime use,
      and that of benzodiazepines had similar percentages in Brazil (3.3%) and in the
      USA (5.8%). In this survey, only four individuals reported lifetime use of
      heroin, which was equivalent to about 0.04% of the sample and much lower than
      that in the USA with 1.2% and in Colombia reaching 1.5%. These findings will
      allow the implementation of public policies fitted to the situation with
      psychotropic drugs in Brazil.

PMID- 15718071
TI  - Depression vulnerability, cigarette smoking, and the serotonin transporter gene.
AB  - People with current or past depression are more likely to have been smokers at
      some point in their lives. Smokers with depression histories are also less likely
      to quit. Attempts to understand this relationship are important insofar as they
      can help treatment efficacy for this group of smokers. Prior research indicates
      that different genetic variations affect the relationship between smoking and
      neuroticism. This study examined whether people with a short serotonin
      transporter genotype would likewise show a stronger relationship between
      depression vulnerability and smoking behavior than those with the long genotype.
      Although depression vulnerability was associated with smoking behaviors, genotype
      did not significantly affect this relationship. Discussion centered on possible
      reasons for varying results across conceptually similar studies.

PMID- 15718072
TI  - Evaluating anxiety sensitivity, exposure to aversive life conditions, and
      problematic drinking in Russia: a test using an epidemiological sample.
AB  - The present study evaluated the main and interactive effects of anxiety
      sensitivity (AS) and exposure to aversive conditions in terms of their
      association with alcohol consumption and problems in an epidemiologically defined
      sample from Russia (N=345). Results revealed a positive association between
      stress exposure and problematic drinking. The findings also indicated that
      individuals with low anxiety sensitivity evidence more problematic drinking if
      they were exposed to more aversive conditions. In contrast, individuals with high
      anxiety sensitivity reported less problematic drinking if they were exposed to
      more aversive conditions. Although these findings are only partially consistent
      with original prediction, they suggest a novel, potentially important interplay
      between the processes that contribute to alcohol use problems among individuals
      susceptible to anxiety psychopathology.

PMID- 15718073
TI  - Challenges in measuring concurrency, agency and intentionality in polydrug
      research.
AB  - Polydrug use is of particular interest to researchers concerned with the drug use
      of youth and young adults because it is associated with progression to regular
      and addictive drug use. New research shows that polydrug use appears to be taking
      new forms as youth use multiple drugs concurrently in the same setting, sometimes
      to achieve specific desired effects. Existing approaches to measuring polydrug
      use are confusing and inconsistent. This paper calls for new ways of measuring
      polydrug use that capture concurrency in context to obtain more accurate
      assessments of drug mixing and its potential physical and social effects.

PMID- 15718074
TI  - The Fagerstrom Test for Nicotine Dependence in a Dutch sample of daily smokers
      and ex-smokers.
AB  - We explored the performance of the Fagerstrom Test for Nicotine Dependence (FTND)
      in a sample of 1378 daily smokers and 1058 ex-smokers who participated in a
      survey study of the Netherlands Twin Register. FTND scores were higher for
      smokers than for ex-smokers. Nicotine dependence level was not associated with
      age. FTND score was highly correlated with the maximum number of cigarettes
      smoked (even after excluding the item 'number of cigarettes per day' from FTND),
      but the FTND score showed a low correlation with age of first cigarette and total
      number of years smoked. In a subsample of smokers (n = 143) and ex-smokers (n =
      181) the test-retest correlations for the FTND were high. In general, the
      performance of the FTND in ex-smokers was comparable with that in smokers. These
      findings suggest the FTND to be a valuable tool for studies of nicotine
      dependence in large epidemiological samples.

PMID- 15718075
TI  - Current heavy drinkers' reasons for considering change: results from a natural
      history general population survey.
AB  - Current heavy drinkers were recruited from a general population random-digit
      dialing telephone survey. Comparisons were made between those who were
      considering or not considering change. Those considering reducing or quitting
      their drinking in the next 6 months were asked their reasons for considering
      change. Respondents considering change had more severe alcohol problems and
      perceived more risk associated with their drinking as compared with those not
      considering change. The most common reasons for considering change were health
      and financial concerns.

PMID- 15718076
TI  - Risky sex and drinking contexts in freshman first offenders.
AB  - Two hundred and seventy-six sexually active college freshmen were surveyed as
      part of an adjudication process for having violated university substance abuse
      guidelines. This study examined the relationship between drinking contexts and
      risky sex while controlling for problem drinking. Results demonstrated that
      drinking excessively in intimate situations was significantly associated with
      greater expectancies of alcohol's sex-enhancing effects and with risky sexual
      behaviors (RSB). In addition, risky sex expectancies (RSE) and behaviors were
      higher among males who drank excessively to cope with negative emotions.
      Implications for early intervention are noted.

PMID- 15718077
TI  - The effects of a prison smoking ban on smoking behavior and withdrawal symptoms.
AB  - This study investigated symptoms of distress and nicotine dependence as
      predictors of nicotine withdrawal symptoms among 188 incarcerated male smokers
      during a mandated smoking ban. Participants completed a smoking history
      questionnaire and measures of nicotine dependence, withdrawal, cravings, and
      distress before the ban and two follow-up times. The majority of smokers (76%)
      continued to smoke following the smoking ban. Smokers after the ban were more
      nicotine dependent than were the participants who reported quitting. Smokers also
      reported more withdrawal symptoms than did participants who quit, even when
      accounting for nicotine dependence and baseline withdrawal scores. An interaction
      was found such that distressed smokers had the highest level of nicotine
      withdrawal. These results have implications for how smoking bans are instituted
      in prison settings.

PMID- 15718078
TI  - Predicting alcohol and drug abuse in Persian Gulf War veterans: what role do PTSD
      symptoms play?
AB  - This study is a prospective longitudinal examination of symptoms of drug and
      alcohol use (SUD) and PTSD symptoms in 1006 veterans in the 6 years (T3)
      following return from the Persian Gulf War (PGW). Both alcohol and drug use at T3
      were significantly correlated with demographic variables and all three types of
      PTSD symptoms (reexperiencing, avoidance, and arousal) as measured at T2.
      Hierarchical regressions were conducted to examine the self-medication
      hypothesis, which was supported for drug use but not for alcohol use at T3.

PMID- 15718079
TI  - Weight concerns and smoking in Black and White female smokers.
AB  - We examined whether the weight concerns of Blacks and Whites who enroll in
      smoking-cessation treatment differed from women who declined treatment. Black
      (n=100) and White (n=100) female smokers completed four measures of weight
      concern. Whites reported more general weight concern and smoking-specific weight
      concern than Blacks did. Treatment enrollers reported more general and smoking
      specific weight concerns than decliners did. After controlling for BMI, SES, and
      number of cigarettes, ethnicity accounted for significant variance in general and
      smoking-specific weight concerns. Overall, Blacks reported less weight concerns
      than the Whites did, but when Blacks enrolled in treatment, these differences
      were less apparent.

PMID- 15718080
TI  - Validation of retrospective reports of early experiences with smoking.
AB  - Initial sensitivity to the pharmacological effects of a drug may affect patterns
      of future use and dependence for a wide variety of drugs. Retrospective reports
      of sensations experienced upon early experimentation, however, may be limited by
      recall bias based on time elapsed and subsequent experiences. To validate reports
      of early experiences with nicotine, we studied 34 smokers who had contributed
      retrospective data on early experiences with smoking. Half had reported
      experiencing a buzz from smoking their first cigarette (the "yes" group), the
      other half had not (the "no" group). To simulate initial sensitivity to nicotine,
      we asked participants to remain abstinent from smoking for 5 days to allow for
      the dissipation of tolerance. They then participated in a laboratory session in
      which they were reexposed to nicotine in an unfamiliar form (nicotine nasal
      spray) and asked to indicate pleasurable responses by depressing a foot pedal if
      and when they experienced a "pleasurable buzz." Smokers in the "yes" group were
      marginally more likely to be male. The two groups did not differ significantly on
      age or race. The "yes" group smoked significantly more cigarettes/day than the
      "no" group. When the two groups were compared for response to nasal spray
      following 5 days' abstinence, smokers in the "yes" group were marginally more
      likely to have signaled experiencing at least one pleasurable buzz and rated
      "pleasurable sensation from spray" on a 100-mm visual analogue scale administered
      10 min after nicotine dosing significantly higher than were those in the "no"
      group. To the extent that several days' abstinence can serve as a model for
      initial sensitivity to nicotine, our findings validate retrospective reports of
      pleasurable sensations upon early smoking experimentation.

PMID- 15718081
TI  - Validity of retrospective assessments of nicotine dependence: a preliminary
      report.
AB  - Information about levels of nicotine dependence in ex-smokers when they smoked,
      or in current smokers at an earlier date, is useful for clinical and research
      purposes. To estimate the accuracy of retrospective reports of dependence, 28
      individuals who completed either the Fagerstrom Tolerance Questionnaire (FTQ) or
      Fagerstrom Test for Nicotine Dependence (FTND) in smoking cessation trials
      conducted 5 to 12 years earlier were asked to respond again to the same
      questions, thinking back to their smoking behavior just prior to their on-study
      quit attempt. Concordance and Kappa values for the items ranged from 50.0% to
      95.0% and 0.00 to 0.92, respectively. The mean difference between the baseline
      and follow-up total scale scores was 0.05 for the FTQ and 0.38 for the FTND, and
      the correlation between these assessments was 0.62 for the FTQ (p<0.005) and 0.72
      for the FTND (p<0.05). These preliminary results suggest that retrospectively
      assessed FTQ/FTND scale scores have acceptable reliability.

PMID- 15718082
TI  - Self-reported driving behaviour and attitudes towards driving under the influence
      of cannabis among three different user groups in England.
AB  - The study characterized self-reported driving behaviour, attitudes towards
      driving and assumptions about the effects of cannabis on driving, among two
      different volunteer groups: 63 regular cannabis users (RCUs; cannabis
      use>monthly) and 46 undergraduate student users, all from the West Midlands. More
      detailed information was provided by structured interviews with an additional
      sample of 23 regular users from southern England. Within each group, many
      respondents had driven whilst under the influence of cannabis (regular users,
      82%; students, 40%; interviewees, 100%). Majorities among the regular users and
      interviewees continued to do so at least monthly. Most users believed that
      cannabis impaired driving only slightly. More stops by the police for drug
      driving than for drink-driving were reported, but these rarely resulted in
      conviction and were not deterrent. Hence, cannabis users are very willing to
      drive after using the drug (often combined with alcohol), and even while
      intoxicated. They consider its effects on driving to be minimal; indeed, many
      consider it to promote better driving. Attitudes towards drink-driving were much
      more negative. Finally, most interviewees said that roadside drug testing would
      be the only efficacious deterrent to drug-driving.

PMID- 15718084
TI  - General principles of surgery applied to cattle.
AB  - Basic principles of surgery are important to review, even for experienced
      surgeons. Although aseptic surgical principles are not always applicable in the
      field, we have to respect some guidelines. Recent research will influence the way
      that we do things, based on what we have been taught and our experience.
      Respecting those simple principles can make a big difference in the final
      outcome.

PMID- 15718085
TI  - Pain management in ruminants.
AB  - Based on the available literature, the most important tool available in modern
      veterinary medicine is preemptive analgesia. Veterinarians must capture
      "opportunities" to prevent the onset of pain, prevent noxious stimuli or their
      perception, and limit the pain-stress-distress cascade that results in altered
      behavior and deviation from physiologic norms. Rational treatment of pain
      requires an appreciation of its consequences, a fundamental understanding of the
      mechanisms that are responsible for its production,and a practical appreciation
      of the analgesic drugs that are available. The goal of pain treatment should be
      to restore normal (physiologic) pain responses and to eliminate pathologic pain
      processes. In this context, pain therapy should be directed at the multiple
      mechanisms (multimodal therapy)responsible for its production, and analgesic
      therapies should be instituted before (preemptive therapy) pain is initiated (eg,
      surgery) whenever possible.

PMID- 15718086
TI  - Ultrasound as a decision-making tool in abdominal surgery in cows.
AB  - In many patients, abdominal ultrasonography is an excellent diagnostic and
      prognostic tool. It aids in deciding whether the animal should undergo surgical
      or medical treatment or be slaughtered. This is particularly true in cattle with
      traumatic reticuloperitonitis (in combination with radiography of the reticulum)
      or with a tentative diagnosis of left or right displacement of the abomasum.
      Ultrasound also is an excellent aid for identification of ileus of the small and
      large intestine, liver abscesses, cholestasis, various urinary tract disorders,
      and the different forms of ascites.

PMID- 15718087
TI  - Routine surgical procedures in dairy cattle under field conditions: abomasal
      surgery, dehorning, and tail docking.
AB  - This article discusses the different methods used for the correction of left
      displaced abomasum. The advantages, disadvantages, and success rates of each
      technique are reviewed. The most common complications are described, and the
      economics of repeat surgery after a failed left displaced abomasum repair are
      examined. This article also addresses the need for anesthesia when dehorning and
      tail docking dairy cattle. The justifications for routine use of these two
      procedures are discussed, mainly from an animal welfare standpoint.

PMID- 15718089
TI  - Surgical abdomen of the calf.
AB  - Although underrepresented compared with infectious diseases, calves' surgical
      abdomen diseases and abdominal surgery are a part of daily veterinary practice.
      Clinical presentations may differ from adult cattle and change rapidly. The
      decision whether to perform abdominal surgery or refer the animal has to take
      into consideration the condition and its prognosis for the calf. This article
      discusses clinical presentation of calves and focuses on specific situations with
      a detailed description of the surgical techniques, atresia coli, and umbilical
      remnants infection.

PMID- 15718088
TI  - Cesarean section in cows.
AB  - The goals of the cesarean section are preservation of the dam and calf and the
      future reproductive efficiency of the dam. The outcome of the cesarean section is
      a self-fulfilling prophecy. Numerous variables may affect the successful outcome
      of this procedure. Case selection is the most important and often overlooked
      variable. In addition, skin preparation,surgical technique, calf viability at the
      time of surgery, and exteriorizing the uterus can affect outcome. Minimizing
      excessive adhesion formation is equally important because it may affect
      reproductive efficiency adversely. Good surgical technique, including gentle
      tissue handling, appropriate suture materials and patterns, and adequate
      infolding of the uterine incision to prevent leakage, combined with antibiotics
      and anti-inflammatories when indicated can help minimize detrimental adhesions
      that may affect adversely the future reproductive efficiency of the cow. When
      dealing with anemphysematous fetus, intensive medical management perioperatively
      isa crucial determining factor of cow survival. Anti-inflammatories, high doses
      of intravenous antibiotics, and a ventral midline approach that permits adequate
      uterine exteriorization and reduces abdominal contamination also are likely key
      elements that contribute to the high survival rates of cows with emphysematous
      fetuses.

PMID- 15718090
TI  - Intestinal surgery of adult cattle.
AB  - Surgical disorders of the gastrointestinal tract of cattle occur occasionally,
      and veterinarians are challenged to determine an accurate diagnosis and treatment
      for these conditions. Although surgical diseases most commonly occur in the
      forestomachs (dislocated abomasum, reticuloperitonitis) and the colons (cecal
      dilation), this article focuses n lesions in the small intestine (duodenum,
      jejunum, ileum).

PMID- 15718091
TI  - Management of peritonitis in cattle.
AB  - Peritonitis commonly is included in a list of differential diagnoses in food
      animal practice. Understanding the physiology of the ruminant peritoneal cavity
      and its response to injury is important to institute an adequate therapeutic
      plan. Ancillary procedures are used often and are necessary to confirm the
      diagnosis and should be well-organized.

PMID- 15718092
TI  - Procedures and surgeries of the teat.
AB  - Injuries to the end of the teat are frequent and frustrating to treat. Treatment
      of these injuries evolved from being aggressive using teat knives to a more
      conservative approach employing rest nonreactive teat inserts. The process of
      milking seems simple, but it involves fine-tuned mechanics. Teat fibrosis, even
      when small, has a disastrous effect on the production life of an animal. There is
      no place for error; any surgical intervention should be precise and aim for
      perfection. Medical imaging techniques and minimally invasive surgery help the
      surgeon to make the best decision. Finally, more investigation is needed to treat
      varicose veins to understand the origin and develop better treatment. Teat
      injuries have drawn more attention more recently. Surgical interventions are
      better planned, and blind treatment with unsuitable teat knives is avoided.
      Treatment of superficial of full-thickness teat lacerations does not require a
      high level of anatomic or surgical knowledge, although basic surgical principles
      should be applied. Hemostasis, delicate debridgement and tissue handling, and
      appropriate suture materials and patterns are key to success. Appropriate
      sedation, anesthesia, and analgesia are essential to achieve this goal and should
      never be neglected.

PMID- 15718093
TI  - Teat endoscopy (theloscopy) for diagnosis and therapy of milk flow disorders in
      dairy cows.
AB  - Teat endoscopy (theloscopy) is a useful technique for diagnosis and therapy of
      covered teat injuries. Minimal invasive theloscopic surgery may help to restore
      milk flow, milk yield, and SCC of the affected quarter. Infection with pathogens
      may not change significantly, however. Cows treated as described may yield as
      much milk as their herdmates at a slightly increased udder SCC and stay as long
      in the herd as their herdmates. Theloscopy also may be used for diagnosis and
      therapy of various other teat disorders.

PMID- 15718094
TI  - General principles of laparoscopy.
AB  - Laparoscopic surgery is minimally invasive and minimally traumatic in cattle. It
      allows the animal to return rapidly to production. These techniques are destined
      to develop further, especially in the dairy and show cattle industries, where
      recovery periods must be as short as possible. Although it is important to remain
      skeptical about new procedures if they do not offer advantages over open
      techniques, in many cases laparoscopy is clearly superior. Laparoscopy is not an
      easy surgical technique. It requires a good knowledge of anatomy and abdominal
      topography and rigorous training. It must be performed with great care and
      delicacy because complications, such as perforated organs, can occur. Laparoscopy
      also requires the use of sophisticated and costly technology.

PMID- 15718095
TI  - Laparoscopic surgery in adult cattle.
AB  - Laparoscopy in cattle is a promising tool for clinical diagnosis and treatment.
      The lower cost of the materials available in addition to the possibility of an
      intervention on an animal that is sedated does not entail more costs than an
      exploratory laparotomy. The application of this tool during abdominal
      explorations and biopsies allows the avoidance of invasive and often useless
      surgical interventions and even with the diagnosis and prognosis of certain
      conditions. Surgical techniques currently are limited to abomasopexies; however,
      never-ceasing progress and improvements in human surgery are expected to affect
      the future of bovine surgery. With the advancements in the multimedia technology
      used by universities, the use of laparoscopy as a pedagogic tool definitely has a
      promising future. Endoscopic exploration of the thorax is possible using the same
      material as for laparoscopy. In addition, diagnostic and biopsy applications are
      useful. The use of the laparoscope in different body cavities and for different
      applications would make the purchase of the required materials more cost
      effective.

PMID- 15718097
TI  - Detecting false expression signals in high-density oligonucleotide arrays by an
      in silico approach.
AB  - High-density oligonucleotide arrays have become a popular assay for concurrent
      measurement of mRNA expression at the genome scale. Much effort has been devoted
      to the development of statistical analysis tools aimed at reducing experimental
      noise and normalizing experimental variation in gene expression analysis.
      However, these investigations do not detect or catalog systematic problems
      associated with specific oligonucleotide probes. Here, we present an
      investigation of problematic probes that yield consistent but inaccurate signals
      across multiple experiments. By evaluating data integrity among gene, probe
      sequence, and genomic structure we identified a total of 20,696 (10.5%)
      nonspecific probes that could cross-hybridize to multiple genes and a total of
      18,363 (9.3%) probes that miss the target transcript sequences on the Affymetrix
      GeneChip U95A/Av2 array. The numbers of nonspecific and mistargeted probes on the
      U133A array are 29,405 (12.1%) and 19,717 (8.0%), respectively. The poor
      performance of the mistargeted probes was confirmed in two GeneChip experiments,
      in which these probes showed a 20-30% decrease in detecting present signals
      compared with normal probes. Comparison of qualitative expression signals
      obtained from SAGE and EST data with those from GeneChip arrays showed that the
      consistency of the two platforms is 30% lower in problematic probes than in
      normal probes. A Web application was developed to apply our results for improving
      the accuracy of expression analysis.

PMID- 15718096
TI  - Mouse protein arrays from a TH1 cell cDNA library for antibody screening and
      serum profiling.
AB  - The mouse is the premier genetic model organism for the study of disease and
      development. We describe the establishment of a mouse T helper cell type 1
      (T(H)1) protein expression library that provides direct access to thousands of
      recombinant mouse proteins, in particular those associated with immune responses.
      The advantage of a system based on the combination of large cDNA expression
      libraries with microarray technology is the direct connection of the DNA sequence
      information from a particular clone to its recombinant, expressed protein. We
      have generated a mouse T(H)1 expression cDNA library and used protein arrays of
      this library to characterize the specificity and cross-reactivity of antibodies.
      Additionally, we have profiled the autoantibody repertoire in serum of a mouse
      model for systemic lupus erythematosus on these protein arrays and validated the
      putative autoantigens on highly sensitive protein microarrays.

PMID- 15718098
TI  - Application of functional genomic technologies in a mouse model of retinal
      degeneration.
AB  - Generation of tissue-specific, normalized and subtracted cDNA libraries has the
      potential to characterize the expression of rare transcriptional units not
      represented on Affymetrix GeneChips. Initial sequence analysis of our murine cDNA
      clone collections showed that as much as 86, 45, and 30% of clones are not
      represented on the Affymetrix Mu11k, MG-U74, and MG-430 chip sets, respectively.
      A detailed study that compared EST sequences of a subtracted library generated
      from mouse retina to those of MG-430 consensus sequences was undertaken, using
      UniGene build 124 as the common reference. A set of 1111 nonredundant transcript
      regions, not represented on the commercial array, was identified. These clusters
      were used as the primary filter for analyzing a data set produced by assaying
      samples from the Pde6b(rd1) mouse model of retinal degeneration on a 12,325
      feature retinal cDNA microarray. QRT-PCR validated eight unique transcripts
      identified by microarray. Seven of the transcripts showed retina-specific
      expression. Full-length cloning strategies were applied to two of the ESTs. The
      genes discovered by this approach are the full-length mouse homologue of
      guanylate cyclase 2F (GUCY2F) and a carboxy-truncated splice variant of retinal S
      antigen (SAG), known as regulators of the visual phototransduction G-protein
      coupled receptor-mediated signaling pathway. These sequences have been assigned
      GenBank Accession Nos. and , respectively.

PMID- 15718099
TI  - A 6-Mb contig-based comparative gene and linkage map of the rat schwannoma tumor
      suppressor region at 10q32.3.
AB  - Frequent genetic aberrations of malignant schwannomas induced by the alkylating
      agent N-ethyl-N-nitrosourea in hybrids from inbred BD rat strains include allelic
      imbalances of the telomeric 20 Mb of chromosome 5 (Dis-2) and of the telomeric 5
      Mb of chromosome 10q32 (Dis-1) in 59 and 94% of the tumors, respectively. The Dis
      1 minimal loss of heterozygosity consensus region extends from D10Rat4 to the
      telomere and harbors a putative tumor suppressor gene(s). We constructed a 6-Mb
      BAC/PAC contig containing more than 70 known genes, 18 mapped microsatellites,
      and further ESTs/reference RNAs. A continuous block of strongly conserved synteny
      with mouse chromosome 11E2 and human chromosome 17q25.3 was found. Combining the
      sequence information from the rat and closely related syntenic regions of
      different mammalian species produces nearly complete gene maps as a basis for a
      positional candidate approach and gives insight into mammalian genomic evolution.

PMID- 15718100
TI  - Positional cloning of the Ttc7 gene required for normal iron homeostasis and
      mutated in hea and fsn anemia mice.
AB  - Genes playing essential roles in iron homeostasis have yet to be identified. We
      report the discovery of a strong candidate gene affecting iron homeostasis in two
      allelic anemia mouse mutants: hea (hereditary erythroblastic anemia) and fsn
      (flaky skin). To clone this novel gene positionally, we established a large
      backcross, which generated a critical region of seven genes from which only one
      gene exhibited a mutation in hea mice. This was a deletion in Ttc7
      (tetratricopeptide repeat domain 7) extending from exon 1 to exon 14.
      Correspondingly, the allelic variant fsn mice showed a mutation of an ETn
      retrotransposon integration into intron 14 of the Ttc7 gene, which results in an
      abnormal Ttc7 RNA transcript. TTC7 is a member of the TPR repeat protein family
      known to interact with other proteins, to facilitate transport, and to act as
      chaperone or scaffolding proteins. We speculate that TTC7 plays an important role
      in iron transport.

PMID- 15718101
TI  - PRR5 encodes a conserved proline-rich protein predominant in kidney: analysis of
      genomic organization, expression, and mutation status in breast and colorectal
      carcinomas.
AB  - Loss of heterozygosity on chromosome 22q13.31 is a frequent event during human
      breast and colorectal carcinogenesis. Herein we characterize a novel gene at
      chromosome 22q13.31 designated PRR5. Alternative promoter usage and splicing
      converge to generate five PRR5 transcript variants with maximum mRNA expression
      in kidney. In vitro transcription/translation demonstrated that the five variants
      generate three protein isoforms differing in their N-terminal length. Mutational
      analysis of PRR5 in human breast and colorectal tumors did not reveal somatic
      mutations. However, mRNA expression analyses revealed PRR5 overexpression in a
      majority of colorectal tumors but substantial downregulation of PRR5 expression
      in a subset of breast tumors and reduced expression in two breast cancer cell
      lines. Treatment with trichostatin A increased PRR5 mRNA levels in BT549 and MDA
      MB-231 cells, whereas 5'-aza-2'-deoxycytidine induced expression in MDA-MB-231
      cells only. Thus, PRR5 may represent a potential candidate tumor suppressor gene
      in breast cancer.

PMID- 15718102
TI  - Molecular cloning, characterization, and chromosomal assignment of porcine
      cationic amino acid transporter-1.
AB  - We have cloned and characterized the gene encoding the porcine cationic amino
      acid transporter, member 1 (CAT-1) (HGMW-approved gene symbol SLC7A1) from
      porcine pulmonary artery endothelial cells. The porcine SLC7A1 encodes 629
      deduced amino acid residues showing a higher degree of sequence similarity with
      the human counterpart (91.1%) than with the rat (87.3%) and mouse (87.6%)
      counterparts. Confocal microscopic examination of porcine CAT-1-GFP-expressing
      HEK293 cells revealed that porcine CAT-1 localizes on the plasma membrane. Amino
      acid uptake studies in Xenopus oocytes injected with cRNA encoding this protein
      demonstrated transport properties consistent with system y(+). Radiation hybrid
      mapping data indicate that the porcine SLC7A1 maps to the distal end of the short
      arm of pig chromosome 11 (SSC11). This map location is consistent with the known
      conservation of genome organization between human and pig and provides further
      confirmation that we have characterized the porcine orthologue of the human
      SLC7A1.

PMID- 15718103
TI  - Evolutionarily conserved non-AUG translation initiation in NAT1/p97/DAP5
      (EIF4G2).
AB  - Only a few cases of exclusive translation initiation at non-AUG codons have been
      reported. We recently demonstrated that mammalian NAT1 mRNA, encoded by EIF4G2,
      uses GUG as its only translation initiation codon. In this study, we identified
      NAT1 orthologs from chicken, Xenopus, and zebrafish and found that in all
      species, the GUG codon also serves as the initiation codon. In all species, the
      GUG codon fulfilled the reported requirements for non-AUG initiation: an optimal
      Kozak motif and a downstream hairpin structure. Site-directed mutagenesis showed
      that nucleotides at positions -3 and +4 are critical for the GUG-mediated
      translation initiation in vitro. We found that NAT1 orthologs in Drosophila
      melanogaster and Halocynthia roretzi also use non-AUG start codons, demonstrating
      evolutionary conservation of the noncanonical translation initiation.

PMID- 15718104
TI  - Trace amine-associated receptors form structurally and functionally distinct
      subfamilies of novel G protein-coupled receptors.
AB  - Trace amines are endogenous compounds structurally related to classical biogenic
      amines that have been studied for decades, triggered by their link to psychiatric
      conditions of high epidemiological and economical relevance. The understanding of
      their pharmacology on the molecular level was hampered until the recent discovery
      of trace-amine-specific receptors. We completed the identification of all members
      of this novel GPCR family in human, chimpanzee, rat, and mouse and observed
      remarkable interspecies differences, even between human and chimpanzee. The
      analysis of the chromosomal localizations, phylogenetic relationships, and ligand
      pocket vectors reveals three distinct receptor subfamilies. As most of these
      receptors do not respond to trace amines, each subfamily will presumably have a
      distinct pharmacological profile, which remains to be identified. We propose a
      uniform nomenclature describing this novel GPCR family in all mammalian species
      as trace-amine-associated receptors (TAARs), which resolves the ambiguities and
      contradictions of the previous naming.

PMID- 15718105
TI  - Ubiquitously expressed GPCR membrane-trafficking orthologs.
AB  - Olfactory receptors are a diverse set of G-protein-coupled receptors (GPCRs) that
      localize to cellular plasma membranes in the olfactory epithelium. Associated
      trafficking proteins often assist in targeting these GPCRs to the membrane,
      facilitating function. One such trafficking protein has been isolated as a mutant
      defective for both odorant response and proper receptor localization in
      Caenorhabditis elegans. This gene (ODR-4) allows for functional expression of
      olfactory receptors in heterologous cells that are otherwise incapable of
      targeting. We have isolated a full-length human cDNA that is homologous to the C.
      elegans gene at the protein level across nearly the entire gene by using a novel
      RecA-based gene enrichment procedure. This sequence is homologous to a family of
      orthologs that share predicted structural features, indicating a conserved
      function. The gene was expressed in 41 of 44 human, mouse, and rat tissues,
      suggesting an important role in trafficking olfactory and other GPCRs.

PMID- 15718106
TI  - High-resolution analysis of chromosomal imbalances using the Affymetrix 10K SNP
      genotyping chip.
AB  - Array-based comparative genome hybridization is a powerful tool for detecting
      chromosomal imbalances at high resolution. However, the design and setup of such
      arrays are time consuming and expensive and thus worthwhile only when large
      numbers of arrays will be processed. To provide a feasible solution, we have
      developed an algorithm that renders the publicly available Affymetrix 10K SNP
      genotyping chip useful for high-resolution analysis of chromosomal imbalances. We
      have used our newly developed algorithm to analyze data from Affymetrix 10K chips
      that were hybridized with DNA probes from a variety of different sources, such as
      primary tumors, cell lines, and blood from patients with unbalanced
      translocations. In summary, we were able to (i) demonstrate the capability of our
      method by reproduction of published and unpublished data obtained with
      alternative methods and (ii) identify novel imbalances that were not shown
      before.

PMID- 15718107
TI  - Coupled analysis of gene expression and chromosomal location.
AB  - Microarray technology can be used to assess simultaneously global changes in
      expression of mRNA or genomic DNA copy number among thousands of genes in
      different biological states. In many cases, it is desirable to determine if
      altered patterns of gene expression correlate with chromosomal abnormalities or
      assess expression of genes that are contiguous in the genome. We describe a
      method, differential gene locus mapping (DIGMAP), which aligns the known
      chromosomal location of a gene to its expression value deduced by microarray
      analysis. The method partitions microarray data into subsets by chromosomal
      location for each gene interrogated by an array. Microarray data in an individual
      subset can then be clustered by physical location of genes at a subchromosomal
      level based upon ordered alignment in genome sequence. A graphical display is
      generated by representing each genomic locus with a colored cell that
      quantitatively reflects its differential expression value. The clustered patterns
      can be viewed and compared based on their expression signatures as defined by
      differential values between control and experimental samples. In this study,
      DIGMAP was tested using previously published studies of breast cancer analyzed by
      comparative genomic hybridization (CGH) and prostate cancer gene expression
      profiles assessed by cDNA microarray experiments. Analysis of the breast cancer
      CGH data demonstrated the ability of DIGMAP to deduce gene amplifications and
      deletions. Application of the DIGMAP method to the prostate data revealed several
      carcinoma-related loci, including one at 16q13 with marked differential
      expression encompassing 19 known genes including 9 encoding metallothionein
      proteins. We conclude that DIGMAP is a powerful computational tool enabling the
      coupled analysis of microarray data with genome location.

PMID- 15718108
TI  - More than one statistical strategy to assess agreement of quantitative
      measurements may usefully be reported.

PMID- 15718109
TI  - A combination of tests for the diagnosis of dementia had a significant diagnostic
      value.
AB  - OBJECTIVE: To study the diagnostic parameters of a number of instruments for a
      diagnosis of dementia in general practice and the added diagnostic value of these
      tests. STUDY DESIGN AND SETTING: Cross-sectional diagnostic research in general
      practice. PARTICIPANTS: 152 persons aged 65 plus. The Mini-Mental State
      Examination (MMSE), the Clock Drawing Test, the ADMP scale, the Timed Up and Go
      Test, the Extrapyramidal Sign Scale, the Behavior Observation Scale, the Poon
      Baro-Wens computer battery, and the Cognitive Drug Research Computerized
      Assessment System were evaluated against the Dutch version of the Cambridge
      Examination for Mental Disorders of the Elderly (CAMDEX-N). Diagnostic
      characteristics were calculated with their 95% CI. Using forward stepwise
      logistic regression analysis, a model was built with CAMDEX-N as the dependent
      variable and the tests under study as independent variables. Area under the curve
      was the main parameter for the comparisons. RESULTS: The main diagnostic gain
      results from age and ADMP, followed by the Clock Drawing Test. Subsequent
      addition of the MMSE and computer tests results in modest additional gain only.
      The final model including five tests has an area under the curve of 0.95.
      CONCLUSION: Sophisticated neuropsychological computerized tests have little added
      value in the diagnostic work-up of dementia in general practice. Basic clinical
      tests used in an appropriate sequence can be very valuable in establishing the
      diagnosis of dementia.

PMID- 15718110
TI  - Clinical history and biologic age predicted falls better than objective
      functional tests.
AB  - OBJECTIVE: Fall risk assessment is important because the consequences, such as a
      fracture, may be devastating. The objective of this study was to find the test or
      tests that best predicted falls in a population-based sample of elderly women.
      STUDY DESIGN AND SETTING: The fall-predictive ability of a questionnaire, a
      subjective estimate of biologic age and objective functional tests (gait, balance
      [Romberg and sway test], thigh muscle strength, and visual acuity) were compared
      in 984 randomly selected women, all 75 years of age. RESULTS: A recalled fall was
      the most important predictor for future falls. Only recalled falls and intake of
      psycho-active drugs independently predicted future falls. Women with at least
      five of the most important fall predictors (previous falls, conditions affecting
      the balance, tendency to fall, intake of psychoactive medication, inability to
      stand on one leg, high biologic age) had an odds ratio of 11.27 (95% confidence
      interval 4.61-27.60) for a fall (sensitivity 70%, specificity 79%). CONCLUSION:
      The more time-consuming objective functional tests were of limited importance for
      fall prediction. A simple clinical history, the inability to stand on one leg,
      and a subjective estimate of biologic age were more important as part of the fall
      risk assessment.

PMID- 15718111
TI  - Searching the LILACS database for Portuguese- and Spanish-language randomized
      trials in physiotherapy was difficult.
AB  - OBJECTIVE: Evidence-based practice requires access to systematic reviews and
      randomized controlled trials; however, most literature databases index primarily
      English-language journals. We sought to determine the extent and quality of
      Portuguese- and Spanish-language reports of randomized trials relevant to
      physiotherapy by searching the LILACS database (Literatura Latino Americana e do
      Caribe em Ciencias da Saude). A secondary aim was to compare the sensitivity of
      three strategies for searching for Portuguese- and Spanish-language randomized
      trials in physiotherapy. STUDY DESIGN AND SETTING: The LILACS database was
      searched for randomized trials using three search strategies. RESULTS: Three
      search strategies returned 5,262 records, of which only 47 were randomized
      trials. Most trials reported treatments for pain or cardiopulmonary disease, and
      most were of moderate to high quality. The sensitivity of the three search
      strategies varied from 2% to 53%. CONCLUSION: A small number of moderate- to high
      quality randomized trials in physiotherapy are published in Spanish and
      Portuguese languages, but they are difficult to find.

PMID- 15718112
TI  - Random effects survival models gave a better understanding of heterogeneity in
      individual patient data meta-analyses.
AB  - BACKGROUND AND OBJECTIVE: Individual patient data meta-analysis consists in
      combining data from all available trials dealing with a therapeutic problem in
      order to increase the power of statistical analyses. A key issue when analyzing
      these pooled data sets is intertrial heterogeneity. In survival data,
      heterogeneity manifests itself either by differing treatment effects between the
      included trials or by a baseline hazard that differs between studies. One way to
      investigate and accommodate this heterogeneity is to use models that include
      random effects. METHODS: We apply this class of models to the Meta-Analysis of
      Chemotherapy in Head and Neck Cancers, in which strong heterogeneity is
      exhibited. This meta-analysis pooled 63 trials involving 10,741 patients.
      RESULTS: We show that such modeling permits a better understanding of
      heterogeneity in the MACH-NC data, both from a frequentist and from a Bayesian
      point of view. In particular, the modeling suggests the presence of two outlying
      sets of trials whose baseline risk could explain the apparent efficacy or
      inefficacy of some treatment protocols. CONCLUSION: We conclude that this family
      of random-effects models is a useful tool for exploring heterogeneity in meta
      analyses of time-to-event data, and that its features can be applied to a very
      wide range of studies.

PMID- 15718113
TI  - Intraclass correlation coefficient and outcome prevalence are associated in
      clustered binary data.
AB  - BACKGROUND AND OBJECTIVE: To describe the association between values for a
      proportion and the intraclass correlation coefficient (ICC). METHODS: Analysis of
      data obtained from the General Practice Research Database (GPRD) for variation
      between United Kingdom general practices and results from a Health Technology
      Assessment (HTA) review for a range of outcomes in community and health services
      settings. RESULTS: There were 188 ICCs from the GPRD, the median prevalence was
      13.1% (interquartile range IQR 3.5 to 28.4%) and median ICC 0.051 (IQR 0.011 to
      0.094). There were 136 ICCs from the HTA review, with median prevalence 6.5% (IQR
      0.4 to 20.7%) and median ICC 0.006 (IQR 0.0003 to 0.036). There was a linear
      association of log ICC with log prevalence in both datasets (GPRD, regression
      coefficient 0.61, 95% confidence interval 0.53 to 0.69, P < 0.001; HTA, 0.91,
      0.81 to 1.01, P < 0.001). When the prevalence was 1% the predicted ICC was 0.008
      from the GPRD or 0.002 from the HTA, but when the prevalence was 40% the
      predicted ICC was 0.075 (GPRD) or 0.046 (HTA). CONCLUSION: The prevalence of an
      outcome may be used to make an informed assumption about the magnitude of the
      intraclass correlation coefficient.

PMID- 15718114
TI  - Confidence in polymerase chain reaction diagnosis can be improved by Bayesian
      estimation of post-test disease probability.
AB  - OBJECTIVE: Polymerase chain reaction (PCR) techniques allow highly sensitive
      detection of specific DNA for diagnosis of infectious and genetic disease, but
      uncertainty relating to sensitivity and contamination has frequently resulted in
      controversy over results. We propose a new design in which the PCR contamination
      rate is estimated experimentally. The sensitivity of duplicate test results, and
      hence the post-test disease probabilities, can be derived algebraically, but wide
      confidence limits around these point estimates reduce their usefulness. STUDY
      DESIGN AND SETTING: We have developed a Bayesian method which gives better
      estimates of post-test disease probability and can substantially reduce
      uncertainty by using the prior belief that sensitivity is not lower than 90%.
      RESULTS: With 100 duplicate test samples and 100 control samples, we find that
      the post-test disease probability for concordant results (both positive or both
      negative) is generally unequivocal. The post-test disease probability for
      discordant results (one test positive and one negative) is often sufficiently
      clear to allow useful interpretation of individual test results, depending on the
      context. CONCLUSION: Using this approach, the performance of a PCR can be
      evaluated experimentally allowing post-test disease probability to be estimated,
      giving improved confidence in test results.

PMID- 15718115
TI  - Seven items were identified for inclusion when reporting a Bayesian analysis of a
      clinical study.
AB  - OBJECTIVE: (1) To generate a list of items that experts consider most important
      when reporting a Bayesian analysis of a clinical study, (2) to report on the
      extent to which we found these items in the literature, and (3) to identify
      factors related to the number of items in a report. STUDY DESIGN AND SETTING:
      Based on opinions from 23 international experts, we determined the items
      considered most important when publishing a Bayesian analysis. We then performed
      a literature search to identify articles in which a Bayesian analysis was
      performed and determined the extent to which we found these items in each report.
      Finally, we examined the relationship between the number of items in a report and
      journal- and article-specific attributes. RESULTS: Our final set of seven items
      described the prior distribution (specification, justification, and sensitivity
      analysis), analysis (statistical model and analytic technique), and presentation
      of results (central tendency and variance). There was >99% probability that more
      items were reported in studies with a noncontrolled study design and in journals
      with a methodological focus, lower impact factor, and absence of a word count
      limit. CONCLUSION: We developed a set of seven items that experts believe to be
      most important when reporting a Bayesian analysis.

PMID- 15718116
TI  - Guidelines were developed for data collection from medical records for use in
      retrospective analyses.
AB  - OBJECTIVE: To construct a set of guidelines for data collection from medical
      records. STUDY DESIGN AND SETTING: Retrospective analysis of clinical data is
      often performed by physician-scientists. In such research, the source of clinical
      data is the patient's medical record; however, medical records are intended for
      patient care and the data are not systematically recorded for research purposes.
      We drew on recommendations in the literature and our own experience with a
      retrospective cohort study that uses a DNA bank to construct guidelines for data
      collection from medical records. RESULTS: The guidelines incorporate a number of
      strategies for accurate data collection, which are discussed and illustrated by
      application. CONCLUSION: With guidelines for data collection, the quality of
      research data is enhanced. A well-designed case record form and a handbook for
      standardized data collection are essential for training the data collectors and
      for ensuring fastidious searching of the record; however, certain kinds of
      information are not always well documented in patient records. Consequently, it
      is essential to perform a pilot study to assess the study design and to use
      additional questionnaires. Correct interpretation of clinical outcomes documented
      in the medical records often necessitates an independent adjudication committee
      to prevent bias in outcome definition.

PMID- 15718117
TI  - Local and national electronic databases in Norway demonstrate a varying degree of
      validity.
AB  - OBJECTIVE: The aim of the present study was to examine the validity of local and
      national electronic databases using medical records as gold Standard. STUDY
      DESIGN AND SETTING: All hospital admissions with ICD 9-code 820.X (hip fracture)
      in a 1-year period were identified in the electronic discharge registers of the
      hospitals in Oslo and in the national electronic database (The Norwegian Patient
      Register). Medical records for all patients identified by the discharge registers
      and the logbooks of the operating theater of the hospitals were retrieved, and
      the diagnosis was verified. RESULTS: Compared with the total number of fractures
      confirmed in medical records, the electronic discharge register of one of the
      hospitals underestimated the number of fractures by 46%, whereas the two other
      overestimated the number by 17% and 19%. For the national electronic database, an
      overall overestimation of 19% was found. CONCLUSION: The present findings
      question the validity of electronic databases and thus have implications for
      epidemiologic studies.

PMID- 15718118
TI  - Self-report was a viable method for obtaining health care utilization data in
      community-dwelling seniors.
AB  - OBJECTIVE: Patient self-report and audits of medical records are the most common
      approaches for obtaining information on utilization of medical services. Because
      of the time and cost savings associated with self-report, it is important to
      demonstrate the reliability of this approach, particularly in older persons who
      use more medical resources but may have poorer recall. STUDY DESIGN AND SETTING:
      We contacted the medical providers of a random sample of seniors (n = 150) who
      participated in an ongoing study of health care use. Providers' reports on the
      participant's medical utilization in the prior year were compared with patients'
      self-report over the same time period using weighted kappa statistics. RESULTS:
      Perfect or almost perfect agreement (weighted kappa = 0.80-1.00) was obtained for
      physician, hospital, and emergency department visits and high-cost therapies
      (chemotherapy, radiation therapy). Agreement was substantial (weighted kappa =
      0.60-0.80) for x-ray procedures and prescription medications and moderate
      (weighted kappa = 0.40-0.60) for outpatient procedures and diagnostic tests.
      CONCLUSION: Participant self-report is a viable, reasonably accurate method to
      obtain information on most types of medical utilization in an older study cohort.

PMID- 15718119
TI  - Quality-adjusted life years was a poor predictor of women's willingness to pay in
      acute and chronic conditions: results of a survey.
AB  - OBJECTIVE: We investigated the relationship between quality-adjusted life years
      (QALYs) and willingness to pay (WTP) in acute and chronic conditions. STUDY
      DESIGN AND SETTING: Face-to-face interviews were used to collect data in a
      convenience sample of women. Participants completed one interview evaluating
      preferences for an acute condition, post-chemotherapy nausea and vomiting (PCNV),
      and the other interview for a chronic condition (breast cancer). Preferences were
      elicited for QALYs using visual analogue scale (VAS), and standard gamble in
      addition to WTP. Because QALYs and WTP are purportedly based on the same
      underlying theoretical foundations, WTP was regressed onto change in QALYs, age,
      income, and health status. RESULTS: Regression analysis reported statistically
      significant models for all breast cancer (P < .001) and PCNV (P < .05) conditions
      tested. However, QALY was not a significant predictor of WTP. CONCLUSION: The
      results of this study indicate QALYs was a poor predictor of WTP for the
      conditions tested. Linear combinations of change in QALYs, age, income, and
      health status were a better predictor of WTP for chronic than acute conditions.
      This can be attributed to violations of underlying assumptions in measurement of
      QALYs with acute conditions and to problems with the use of WTP with chronic
      conditions.

PMID- 15718120
TI  - A cohort study found that white blood cell count and endocrine markers predicted
      preterm birth in symptomatic women.
AB  - OBJECTIVE: This cohort study investigated potential clinical and biochemical
      predictors of subsequent preterm birth in women presenting with threatened
      preterm labor. STUDY DESIGN AND SETTING: Subjects were 218 pregnant women
      admitted to hospital with a diagnosis of threatened preterm labor at 22-36 weeks
      gestation. Exclusion criteria were multiple pregnancy, fetal anomalies, diabetes
      mellitus, abruptio placenta, preeclampsia, intrauterine growth restriction,
      cervical dilatation > 4 cm, and clinical signs of infection. Analyses used
      logistic regression. RESULTS: The presence of ruptured membranes was the best
      predictor of birth within 48 hours. Other important predictors were maternal
      white blood cell count at 22-27 weeks gestation and maternal adrenocorticotropin
      and corticotropin-releasing hormone concentrations at 28-36 weeks gestation.
      CONCLUSION: Subclinical infection may be an important etiologic factor in preterm
      births of gestational age < 28 weeks. For those at > or = 28 weeks gestation, the
      findings support the etiologic role of activation of the fetal and/or maternal
      hypothalamic pituitary adrenal axis leading to preterm birth.

PMID- 15718121
TI  - An analysis of systematic reviews indicated low incorpororation of results from
      clinical trial quality assessment.
AB  - OBJECTIVE: We investigated the frequency of quality assessment of randomized
      controlled trials within systematic reviews and the incorporation of the quality
      assessment in the analysis. STUDY DESIGN AND SETTING: We included new systematic
      reviews of at least five trials of therapeutic or preventive interventions that
      appeared in issue 2, 2003, of the Cochrane Database of Systematic Reviews. All
      systematic reviews in the 2002 issues of the Annals of Internal Medicine, BMJ,
      JAMA, and Lancet were identified in Pubmed. All reviews were assessed under
      unblinded conditions using preprinted extraction forms. RESULTS: Trial quality
      was assessed in all Cochrane reviews and most (74%) of the paper reviews. When we
      excluded 11 paper reviews that were also published as Cochrane review, the
      percentage remained similar (67%). Fifty percent of all Cochrane reviews and 61%
      of all paper reviews incorporated the results of the quality assessment in the
      analysis. CONCLUSION: Half of the reviews did not incorporate the results of the
      quality assessment in the analysis. Authors, peer-reviewers, and editors should
      no longer focus exclusively on whether quality assessment has been performed but
      should also concentrate on incorporation of quality assessments in the analysis
      of the systematic review.

PMID- 15718122
TI  - Survival analytical techniques were used to assess agreement of a quantitative
      variable.
AB  - BACKGROUND AND OBJECTIVE: Survival-agreement plots have been suggested as a new
      graphical approach to assess agreement in quantitative variables. We propose that
      survival analytical techniques can complement this method, providing a new
      analytical insight for agreement. METHODS: Two survival-agreement plots are used
      to detect the bias between to measurements of the same variable. The presence of
      bias is tested with log-rank test, and its magnitude with Cox regression.
      RESULTS: An example on C-reactive protein determinations shows how survival
      analytical methods would be interpreted in the context of assessing agreement.
      CONCLUSION: Log-rank test, Cox regression, or other analytical methods could be
      used to assess agreement in quantitative variables; correct interpretations
      require good clinical sense.

PMID- 15718123
TI  - A review of medical records and discharge summary data found moderate to high
      predictive values of discharge diagnoses of venous thromboembolism during
      pregnancy and postpartum.
AB  - OBJECTIVE: To validate the discharge diagnoses of venous thromboembolism during
      pregnancy and postpartum, we examined the positive predictive value (PPV) of
      venous thromboembolic (VTE) discharge diagnoses associated with pregnancy or
      puerperium based on 311 cases registered in a Danish population-based hospital
      discharge registry. STUDY DESIGN AND SETTING: Medical records and hospital
      discharge summaries were retrieved and reviewed using a standardized form.
      Standard and pregnancy-specific codes were used for 147 (49%) and 153 (51%)
      cases, respectively. RESULTS: The overall PPV of the selected codes was 87.3%
      (95% confidence interval [CI]: 83.0-90.9). When focusing on confirmed VTE events
      in relation to the pregnancy, the overall PPV was 79.3% (95% CI: 74.3-83.8).
      CONCLUSION: The overall PPVs of pregnancy-related VTE diagnoses were moderate to
      high. The predictive values varied substantially between the individual codes,
      however, and not all the registered VTE events occurred in relation to pregnancy.
      Thus, use of unvalidated registry-based pregnancy-related VTE diagnoses for
      epidemiological research may lead to biased results.

PMID- 15718124
TI  - Should meta-analysts search Embase in addition to Medline?

PMID- 15718127
TI  - New methodologies for measuring protein interactions in vivo and in vitro.
AB  - The identification and characterization of protein interactions is a key topic in
      current life science research; a huge variety of methodologies have been
      established in recent years to expedite research in this area. Generic methods
      have been established for monitoring protein interactions in vivo by protein
      fragment complementation and for screening protein interactions in vitro by
      highly parallel solid-phase techniques. Substantial progress has been made in
      identifying and characterizing interactions with and between membrane proteins.
      Studying protein interactions on the single-molecule level has become an
      important tool for understanding protein function in vivo and in vitro.

PMID- 15718128
TI  - Protein complexes: structure prediction challenges for the 21st century.
AB  - Only a tiny fraction of the many hundreds of known protein complexes are also of
      known three-dimensional structure. The experimental difficulties surrounding
      structure determination of complexes make methods that are able to predict
      structures paramount. The challenge of predicting complex structures is daunting
      and raises many issues that need to be addressed. To produce the best models, new
      prediction methods have to somehow combine partial structures with a mixed bag of
      experimental data, including interactions and low-resolution electron microscopy
      images.

PMID- 15718129
TI  - A systems biology perspective on protein structural dynamics and signal
      transduction.
AB  - The functional dynamics of signal transduction through protein interaction
      networks are determined both by network topology and by the signal processing
      properties of component proteins. In order to understand the emergent properties
      of signal transduction networks in terms of information processing, storage and
      decision making, we not only need to map the so-called 'interactome' but, perhaps
      more importantly, we also have to understand how the structural dynamics of
      constituent proteins shape non-linear responses through cooperativity and
      allostery. Several in silico methods have been developed to identify networks of
      cooperative residues in proteins and help infer their mode of action. Applying
      this type of analysis to important classes of modular signal transduction domains
      should, in principle, allow the function of these proteins to be abstracted in
      terms of their information processing characteristics, permitting better
      comprehension of the systemic properties of biological networks.

PMID- 15718130
TI  - Inhibiting protein-protein interactions using designed molecules.
AB  - Continuing investigations into protein-protein interactions have revealed their
      key role in regulating a wide range of cellular processes. Although efforts to
      modulate these interactions are more challenging and much less mature than work
      on conventional drug discovery pathways, significant progress has been made on
      several fronts. Highlights of recent advances involve peptide-based inhibitors,
      including sidechain and backbone cross-linked agents, and peptide scaffolds, as
      well as small-molecule inhibitors of protein-protein interactions, such as those
      containing terephthalate or bis-imidazole scaffolds.

PMID- 15718131
TI  - Natively unfolded proteins.
AB  - It is now clear that a significant fraction of eukaryotic genomes encode proteins
      with substantial regions of disordered structure. In spite of the lack of
      structure, these proteins nevertheless are functional; many are involved in
      critical steps of the cell cycle and regulatory processes. In general,
      intrinsically disordered proteins interact with a target ligand (often DNA) and
      undergo a structural transition to a folded form when bound. Several features of
      intrinsically disordered proteins make them well suited to interacting with
      multiple targets and to cell regulation. New algorithms have been developed to
      identify disordered regions of proteins and have demonstrated their presence in
      cancer-associated proteins and proteins regulated by phosphorylation.

PMID- 15718132
TI  - The family feud: do proteins with similar structures fold via the same pathway?
AB  - Theoretical and experimental studies of protein folding have suggested that the
      topology of the native state may be the most important factor determining the
      folding pathway of a protein, independent of its specific amino acid sequence. To
      test this concept, many experimental studies have been carried out with the aim
      of comparing the folding pathways of proteins that possess similar tertiary
      structures, but divergent sequences. Many of these studies focus on quantitative
      comparisons of folding transition state structures, as determined by Phi(f) value
      analysis of folding kinetic data. In some of these studies, folding transition
      state structures are found to be highly conserved, whereas in others they are
      not. We conclude that folds displaying more conserved transition state structures
      may have the most restricted number of possible folding pathways and that folds
      displaying low transition state structural conservation possess many potential
      pathways for reaching the native state.

PMID- 15718133
TI  - Directed evolution of proteins for heterologous expression and stability.
AB  - Recent developments have been made in the application of directed evolution to
      achieve the efficient heterologous expression of proteins in Escherichia coli and
      yeast by increasing the stability and solubility of the protein in the host
      environment. One interesting conclusion that emerges is that the evolutionary
      process often improves the stability and solubility of an intermediate
      (apoprotein, proprotein or folding intermediate) that otherwise constitutes a
      bottleneck to functional expression, rather than altering the protein's final
      state.

PMID- 15718134
TI  - Design of model systems for amyloid formation: lessons for prediction and
      inhibition.
AB  - The determination of the physico-chemical principles underlying amyloid
      deposition is fundamental to the identification of therapeutic strategies to
      prevent or cure amyloid-related disorders. Given the complexity of the molecular
      events involved in protein self-association, researchers have designed simplified
      systems that facilitate the discovery of factors that predispose polypeptides to
      amyloid formation and aggregation. These systems have provided valuable knowledge
      about the determinants underlying the structural transitions to the polymeric
      beta-sheet state present in amyloid fibers and in more disordered aggregates. The
      integration of this knowledge is crucial to the identification of the regions
      responsible for the amyloidogenic and aggregating behavior of a given protein.
      The reliable discovery of amyloid-promoting fragments in proteins should have a
      great impact on the development of anti-amyloid agents. Also, methods that
      identify aggregation-prone motifs have a broad range of biotechnological
      applications, such as the improvement of the solubility of recombinant proteins
      for pharmaceutical and industrial purposes, and peptide-based biomaterial
      engineering.

PMID- 15718136
TI  - Unraveling the early steps of prokaryotic replication.
AB  - In prokaryotes, many of the physical mechanisms governing the process of
      initiating DNA replication are now emerging. For example, certain organizational
      features of origins, such as the use of repetitive sequence elements for
      initiator-binding sites, are found throughout bacteria and many archaea. Common
      themes in the regulation of initiation, including origin sequestration by trans
      acting factors, titration of initiator levels by cis- and trans-acting factors,
      and control of initiator function by ATP, also exist. Recent studies have shown
      that prokaryotic initiator structures are both modular and conserved, and have
      begun to reveal how these proteins specifically recognize target DNA sequences.
      These properties probably control initiator self-assembly and DNA remodeling to
      properly fire replication origins.

PMID- 15718137
TI  - Binding and unwinding: SF3 viral helicases.
AB  - The SF3 helicases, distinct from the more prevalent SF1 and SF2 helicases, were
      originally identified in the genomes of small DNA and RNA viruses. The first
      crystal structures of SF3 helicases have been determined, revealing a closer
      structural relationship to AAA+ proteins than to RecA, consistent with their
      participation in replication initiation. In conjunction with origin-binding
      domains, SF3 helicases are responsible for distorting DNA before replication
      forks can be assembled. At these forks, the SF3 helicases act as replicative
      helicases. The simian virus 40 SF3 helicase forms a hexameric ring, anticipated
      to be characteristic of the entire superfamily.

PMID- 15718138
TI  - Bumps in the road: how replicative DNA polymerases see DNA damage.
AB  - Significant advances have been made recently in the study of polymerases. First
      came the realization that there are many more DNA polymerases than originally
      thought; indeed, no fewer than 14 template-dependent DNA polymerases are found in
      mammals. Concurrent structural studies of DNA polymerases bound to DNA and
      incoming nucleotide have revealed how these remarkable copying machines select
      the correct deoxynucleoside triphosphate among a sea of nucleotides. A whole new
      level of insight into DNA replication fidelity has been reached as a result of
      recently determined crystal structures of DNA lesions in the context of the
      active sites of repair, replicative and specialized DNA polymerases. These
      structures illustrate why some lesions can be bypassed readily, whereas others
      are strong blocks to DNA replication.

PMID- 15718139
TI  - Zinc finger proteins: getting a grip on RNA.
AB  - C2H2 (Cys-Cys-His-His motif) zinc finger proteins are members of a large
      superfamily of nucleic-acid-binding proteins in eukaryotes. On the basis of NMR
      and X-ray structures, we know that DNA sequence recognition involves a short
      alpha helix bound to the major groove. Exactly how some zinc finger proteins bind
      to double-stranded RNA has been a complete mystery for over two decades. This has
      been resolved by the long-awaited crystal structure of part of the TFIIIA-5S RNA
      complex. A comparison can be made with identical fingers in a TFIIIA-DNA
      structure. Additionally, the NMR structure of TIS11d bound to an AU-rich element
      reveals the molecular details of the interaction between CCCH fingers and single
      stranded RNA. Together, these results contrast the different ways that zinc
      finger proteins bind with high specificity to their RNA targets.

PMID- 15718140
TI  - Processing the message: structural insights into capping and decapping mRNA.
AB  - The 5' m7GpppN cap plays an essential role in the life cycle of eukaryotic mRNA
      and is required for efficient pre-mRNA splicing, export, stability and
      translation. Nascent pre-mRNA is capped through a series of three enzymatic steps
      that result in a 5' N7-methyl guanosine linked by an inverted 5'-5' triphosphate
      bridge to the first nucleotide of the transcript. Early structural studies
      revealed the mechanisms employed in the first two steps of capping, and more
      recent structural studies have completed the suite of capping activities and shed
      light on the mechanisms that target the capping apparatus to the phosphorylated C
      terminal domain of RNA polymerase II. RNA decay pathways also target the RNA cap
      structure. After deadenylation of polyadenylated mRNA, enzymes of the 5'-3' decay
      pathway hydrolyze the mRNA cap to expose the 5' RNA end to 5'-3' exoribonuclease
      activities. In the 3'-5' decay pathway, exosome-mediated degradation of RNA
      occurs from the 3' end after deadenylation, ultimately generating a cap structure
      that is hydrolyzed by enzymes of this pathway. Recent structural studies have
      illuminated the mechanisms employed for decapping mRNA in both 5'-3' and 3'-5'
      decay pathways.

PMID- 15718141
TI  - Novel modes of protein-RNA recognition in the RNAi pathway.
AB  - Gene silencing mediated by RNA interference (RNAi) depends on short interfering
      RNAs (siRNAs) and micro RNAs (miRNAs). These RNAs have unique features, namely a
      defined size of 19-21 base pairs, and characteristic two-nucleotide single
      stranded 3' overhangs and 5' monophosphate groups. These molecular features of
      siRNAs and miRNAs are produced by RNase III enzymes, which are a hallmark of gene
      silencing induced by double-stranded RNA. Recent structural studies of components
      of the RNAi pathway, including PAZ, Piwi and RNase III domains, as well as full
      length Argonaute and viral p19 proteins, have revealed distinct and novel modes
      of sequence-independent recognition of the characteristic features of siRNAs and
      miRNAs in the RNAi pathway.

PMID- 15718142
TI  - The signal recognition particle and its interactions during protein targeting.
AB  - The synthesis of secretory or integral membrane proteins can be directly coupled
      to their translocation across or insertion into membranes. In co-translational
      targeting, the translation machine, the ribosome, is transferred to the
      respective membrane by the signal recognition particle (SRP) and its receptor
      (SR) as soon as a signal sequence emerges. Protein synthesis can continue at the
      membrane, with the nascent peptide chain directly inserting into the ribosome
      bound protein-conducting channel, the Sec61 complex. During the past two years,
      several structures have been solved by crystallography and cryo-electron
      microscopy that represent distinct functional states of the SRP cycle. On this
      basis, the first structure-based models can be suggested that explain important
      aspects of protein targeting, such as the SRP-ribosome and SRP-SR interactions.

PMID- 15718143
TI  - Structural and functional insight into sugar-nonspecific nucleases in host
      defense.
AB  - In prokaryotes, sugar-nonspecific nucleases that cleave DNA and RNA in a sequence
      independent manner take part in host defense, as well as site-specific
      restriction enzymes. Examples include the periplasmic nuclease Vvn and the
      secreted nuclease ColE7, which degrade foreign nucleic acid molecules in the host
      periplasm and in the cytoplasm of foreign cells, respectively. Recently
      determined crystal structures of Vvn and ColE7 in complex with double-stranded
      DNA provide structural insight into nonspecific DNA interactions and cleavage by
      sugar-nonspecific nucleases. Both nucleases bind DNA at the minor groove through
      a common 'betabetaalpha-metal' endonuclease motif and primarily contact the DNA
      phosphate backbone, probably to avoid sequence-dependent base recognition. In
      eukaryotes, several apoptotic endonucleases that are responsible for DNA
      degradation in programmed cell death also contain a betabetaalpha-metal fold at
      the active site, suggesting that they may recognize and cleave DNA in a
      comparable way.

PMID- 15718144
TI  - Blockade of epidermal growth factor receptor (EGFR) activity.
AB  - The rapidly expanding knowledge of the pathogenesis of cancer at the molecular
      level is providing new targets for drug discovery and development. The key role
      that EGFR plays in the intracellular transduction of environmental variations and
      the maintenance of cellular homeostasis explains the dependence that many tumor
      types have on this pathway, and the pivotal role that it plays in the development
      of malignant features such as uncontrolled proliferation, augmented invasion, and
      the ability to escape apoptosis. An enormous body of knowledge has been gathered
      in the past 20 years that has enabled the development of rationally designed EGFR
      targeted therapies, and the results of their clinical evaluation are now becoming
      available. The lack of positive results of some of these trials has highlighted
      the need for a robust preclinical knowledge in order to efficiently select
      patients for therapy, and have prompted the implementation of novel trial designs
      with rational endpoints.

PMID- 15718145
TI  - Molecular prognostic factors in resectable non-small cell lung cancer.
AB  - Lung cancer retains the leading position in cancer-related deaths in the western
      countries. Non-small cell lung cancer (NSCLC) comprises more than 80% of lung
      cancers, and complete surgical resection of primary tumors in early-stage disease
      is the only potentially curative treatment. One area of intense research on early
      stage NSCLC is the identification of molecular markers to complement TNM staging
      to fully assess the prognosis of patients and to define innovative strategies.
      Numerous prognostic factors have been identified in patients with early-stage
      NSCLC that might enable classification of such patients into different subsets
      corresponding to different risks of recurrence following complete resection. Most
      of the markers are proteins that can be detected by immunohistochemistry assays
      based on the antigen-antibody reaction. The present review aims at providing a
      panorama on classical as well as new prognostic markers. Of special interest are
      some molecular factors, already or currently tested from a prognostic point of
      view, that might also become good candidates for predicting treatment efficacy.

PMID- 15718146
TI  - Primary non-Hodgkin's lymphoma of the liver.
AB  - We review the literature on primary hepatic lymphoma (PHL). PHL is a rare
      malignancy, and constitutes about 0.016% of all cases of non-Hodgkin's lymphoma.
      It has been reported to occur with increased frequency in patients with chronic
      hepatitis C infection. Most patients with PHL present with abdominal pain,
      constitutional symptoms and have hepatomegaly on examination. Imaging studies
      reveal solitary, or less often, multiple masses in the liver. The predominant
      histology is B-cell lymphoma, most commonly diffuse large cell type. Most
      patients are treated with chemotherapy, with some physicians employing a
      multimodality approach incorporating surgery and radiotherapy with chemotherapy.
      The prognosis is variable, with good response to early aggressive combination
      chemotherapy.

PMID- 15718148
TI  - Cutaneous melanoma: pathogenesis and rationale for chemoprevention.
AB  - OBJECTIVE: To critically review aspects of melanoma pathogenesis that lend
      themselves to a chemoprevention strategy. To discuss potential candidate
      chemoprevention agents with an emphasis on the lipid lowering drugs, the statins,
      currently, the most promising agents. DATA SOURCES: A retrospective review of the
      literature. STUDY SELECTION: Studies included those relevant to melanoma
      pathogenesis, to the scientific rationale of chemoprevention, and pertinent
      epidemiologic, pre-clinical, and clinical studies. The referenced study designs
      and methodologies varied. DATA EXTRACTION AND SYNTHESIS: Data were extracted by
      two reviewers, and the main results are presented in a quantitative descriptive
      manner. CONCLUSION: Melanoma is a preventable disease by altering behavior (sun
      exposure) among at-risk individuals. There is also considerable evidence to
      suggest that melanoma development may be prevented or delayed by drugs of
      sufficiently low toxicity to make clinical trials of chemoprevention feasible and
      potentially successful. Among potential candidate agents, statins have compelling
      data for long-term safety and sufficient pre-clinical and clinical evidence for
      efficacy to justify their evaluation in well-designed trials in high-risk
      individuals, incorporating intermediate biologic endpoints.

PMID- 15718147
TI  - Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on
      Japanese experiences.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever and
      hepatosplenomegaly associated with pancytopenia, hypertriglyceridemia and
      hypofibrinogenemia. Increased levels of cytokines and impaired natural killer
      activity are biological markers of HLH. HLH can be classified into two distinct
      forms, including primary HLH, also referred to as familial hemophagocytic
      lymphohistiocytosis (FHL), and secondary HLH. Although FHL is an autosomal
      recessive disorder typically occurring in infancy, it is important to clarify
      that the disease may also occur in older patients. It is now considered that FHL
      is a disorder of T-cell function; moreover, clonal proliferation of T lymphocytes
      is observed in a few FHL patients, and cytotoxicity of these T lymphocytes for
      target cells is usually impaired. In 1999, perforin gene (PRF1) mutation was
      identified as a cause of 20-30% of FHL (FHL2) cases. In Japan, two specific
      mutations of PRF1 were also detected. Furthermore, in 2003, MUNC13-4 mutations
      were identified in some non-FHL2 patients (FHL3). Identification of other genes
      responsible for remaining cases is a major concern. Hematopoietic stem cell
      transplantation (HSCT) has been established as the only accepted curative therapy
      for FHL. Thus, appropriate diagnosis and prompt treatment with HSCT are necessary
      for FHL patients. Genetic analysis for PRF1 and MUNC13-4 and functional assay of
      cytotoxic T lymphocytes are recommended to be performed in each patient. In those
      patients displaying impaired cytotoxic function but lacking genetic defects,
      samples should be employed for identification of unknown genes. In the near
      future, an entire pathogenesis should be clarified in order to establish
      appropriate therapies including immunotherapy, HSCT and gene therapy.

PMID- 15718149
TI  - Temozolomide in the treatment of solid tumours: current results and rationale for
      dosing/scheduling.
AB  - This review examines the current evidence for the use of temozolomide in the
      treatment of solid tumours. The possible molecular and clinical advantages of
      temozolomide are identified and the molecular mechanism of temozolomide
      resistance is explored. Attempts to maximise efficacy have led to manipulation of
      both dosage and drug scheduling and the evidence for the various strategies is
      reviewed. Finally, the potential role of combination therapy is considered.

PMID- 15718150
TI  - Treatments of AIDS-related Kaposi's sarcoma.
AB  - Although Kaposi's sarcoma (KS) has decreased in countries where the highly active
      antiretroviral therapy (HAART) regimen is available, however it remains, after
      non-Hodgkin's lymphomas, the most common malignancy in HIV+ patients. Advances in
      the treatment of AIDS-KS have been achieved, even though a gold standard therapy
      has not been yet defined. With the availability of HAART, a dramatic KS clinical
      response has been documented, making HAART essential in all patients. In case of
      aggressive and/or life threatening KS, more complex therapeutic schedules have to
      be taken into account, including chemotherapy and/or immunotherapy. Liposomal
      anthracyclines and paclitaxel have been approved by FDA as first line and second
      line mono-therapy, respectively. Interferon-alpha (INF-alpha) is the only
      immunomodulant agent to have shown a therapeutic effect. Among the new drugs,
      many antiangiogenetic agents have produced encouraging responses. Finally, the
      identification of the HHV-8 as a causative agent and new metalloproteinase
      inhibitors may offer promising targets for the KS treatment.

PMID- 15718151
TI  - ALS: neighbors matter.

PMID- 15718153
TI  - Singling-out point mutations.
AB  - LigAmp is a new technique for identifying point mutations in DNA and could be a
      new tool for diagnosing and managing diseases.

PMID- 15718152
TI  - New hope for mechanism-based treatment of Parkinson's disease.
AB  - An antibiotic used to treat leprosy is surprisingly effective against Parkinson's
      disease.

PMID- 15718154
TI  - Chris Ashton talks about his career and the recent merger of Argenta Discovery
      and Etiologics. Interview by Steve Carney.
AB  - Chris Ashton describes the driving force behind the merger of Argenta Discovery
      and Etiologics, as well as detailing the highlights and strategies of the
      company's new drug discovery programme.

PMID- 15718155
TI  - Focus on biotechnology in Australia.
AB  - A round-up of the biotechnology industry in Australia.

PMID- 15718156
TI  - New opportunities in Asia: a focus on India and China.
AB  - A focus on IBC's Drug Discovery Technology held in Mumbai, India, on 18-20
      October 2004.

PMID- 15718157
TI  - Chemical grues and little willies.
AB  - Ray Rowe takes a light-hearted look at 'grues', little verses with a twist.

PMID- 15718158
TI  - Perspectives for cytokine antagonist therapy in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease
      associated with progressive airflow limitation. The main risk factor is tobacco
      smoking. Anti-inflammatory therapies (e.g. corticosteroids) are based on those
      developed initially for asthma. In contrast to asthma, they are rather
      ineffective in improving chronic symptoms and reducing inflammation and lung
      function decline. Specific drugs need to be developed directed against this
      chronic inflammation, thereby preventing lung tissue damage. Cytokine antagonists
      for tumour necrosis factor alpha, interleukin 8 receptor, interleukin 1, and
      specific signal transduction inhibitors have proven to be effective for other
      inflammatory diseases. Their efficacy for COPD therapy has yet to be
      demonstrated.

PMID- 15718159
TI  - Thalidomide as a novel therapeutic agent: new uses for an old product.
AB  - Thalidomide and its immunomodulatory analogues have numerous effects on the
      body's immune system, including potential anti-cancer and anti-inflammatory
      activities. Thalidomide is currently used experimentally to treat various
      cancers, dermatological, neurological and inflammatory diseases. This drug is
      approved in the USA for cutaneous manifestations of lepromatous leprosy and is in
      Phase III trials for multiple myeloma. Thalidomide and its analogues modulate the
      immune system in various ways. Some of these immunomodulatory activities,
      together with the anti-angiogenic, anti-proliferative and pro-apoptotic
      properties, are believed to mediate anti-tumor responses as observed in multiple
      myeloma and some solid tumors. The analogue lenalidomide has shown potential in
      treating the bone marrow disorders multiple myeloma and myelodysplastic syndrome,
      and is presently in Phase II and III trials, respectively.

PMID- 15718160
TI  - Timely synthetic support for medicinal chemists.
AB  - In recent years, there have been significant developments made in the way new
      drugs are being discovered and developed. Such changes are driven by new
      technologies that have expanded the opportunities to prepare and screen large
      libraries of compounds in a rapid time frame by the use of high-throughput
      synthesis and screening techniques [1-3]. These strategies are driven by the need
      to shorten time lines for bringing discovery leads to the market [4,5]. As a
      result, the role and needs of synthetic chemistry in the discovery and
      development of new therapeutic agents has been altered [6]. This paper will
      explore the roles of synthetic chemists and how pharmaceutical companies respond
      to the evolving needs of synthetic chemistry challenges in their discovery and
      development programs.

PMID- 15718161
TI  - Targeting DHFR in parasitic protozoa.
AB  - Parasitic apicomplexans are responsible for some of the most severe worldwide
      health problems, including malaria, toxoplasmosis and cryptosporidiosis. These
      parasites are characterized by a bifunctional enzyme, dihydrofolate reductase
      thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine
      biosynthesis. Inhibitors of DHFR have been successful in the treatment of
      toxoplasmosis and malaria. However, there is currently no effective therapy for
      cryptosporidiosis, and despite early successes against malaria, resistance to
      DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR
      inhibitors, designed using the recently revealed crystal structures of the
      enzymes from two parasitic protozoa, are in development.

PMID- 15718162
TI  - Therapeutic scope of modulation of non-voltage-gated cation channels.
AB  - Although widely regarded as attractive drug targets, less than a tenth of known
      ion channels are currently commercially exploited as therapeutic targets.
      Historically, drug discovery efforts on ion channel targets have been encumbered
      by a lack of molecular and structural information, sub-optimal screening
      technologies and a paucity of discriminating pharmacological tools. Although
      challenges remain, recent scientific and technological advances in the area of
      ion channel research and screening offer the exciting prospect of a new, more
      predictive era of ion channel drug discovery. In this article, focusing primarily
      on non voltage gated cation channels, we describe the continuing evolution of
      approaches to ion channel drug discovery, highlight recent developments in the
      ion channel field and consider their potential impact on discovering and
      ascribing function to ion channel targets. We discuss the renaissance of known
      ion channel targets, such as nicotinic acetylcholine receptors and calcium
      activated potassium channels, as well as the emergence of the transient receptor
      potential (TRP) channels as a gene family of cation channels with broad
      therapeutic potential.

PMID- 15718163
TI  - Target-based drug discovery: is something wrong?
AB  - For the past decade the pharmaceutical industry has experienced a steady decline
      in productivity and a striking observation is that the decline coincided with the
      introduction of target-based drug discovery. The target-based approach can very
      effectively develop novel treatments for a validated target, but the process of
      target validation is complex and associated with a high degree of uncertainty.
      The purpose of this paper is to analyse these aspects in detail to determine if
      weaknesses in this part of the drug discovery path might explain why this
      paradigm has not resulted in increased productivity over the traditional in vivo
      approach, considering its superiority in screening capacity and its ability to
      define rational drug discovery programs.

PMID- 15718164
TI  - Predictive in silico modeling for hERG channel blockers.
AB  - hERG-mediated sudden death as a side effect of non-antiarrhythmic drugs has been
      receiving increased regulatory attention. Perhaps owing to the unique shape of
      the ligand-binding site and its hydrophobic character, the hERG channel has been
      shown to interact with pharmaceuticals of widely varying structure. Several in
      silico approaches have attempted to predict hERG channel blockade. Some of these
      approaches are aimed primarily at filtering out potential hERG blockers in the
      context of virtual libraries, others involve understanding structure-activity
      relationships governing hERG-drug interactions. This review summarizes the most
      recent efforts in this emerging field.

PMID- 15718167
TI  - Heart failure management programmes: delivering the message.

PMID- 15718168
TI  - Incidence and outcome of persons with a clinical diagnosis of heart failure in a
      general practice population of 696,884 in the United Kingdom.
AB  - BACKGROUND: There are few large population-based studies of the incidence and
      outcome of heart failure where the diagnosis of heart failure (HF) has been made
      by a General Practitioner (GP) in the community. METHODS: From the General
      Practice Research Database in the UK, we selected a population of 686,884 people
      45 years or older. Incident cases of HF in 1991 were classified definite HF,
      possible HF, or a first prescription of diuretics without a diagnosis of HF. The
      population was followed for 3-year mortality. RESULTS: A total of 6478 patients
      had definite HF (mean age 77.2 years, 55.5% women), 14,050 had possible HF and
      6076 persons were prescribed diuretics without a definite or possible diagnosis
      of HF. The overall incidence of definite HF was 9.3/1000 persons/year and of
      possible HF 20.2/1000 persons/year. Diuretics were prescribed for the first time
      for other reasons for 8.7 persons/1000/year. The incidence of HF was higher in
      men. The incidence of definite HF increased with age. Survival curves showed
      higher mortality rates in the first 3 months after the diagnosis of HF. One-year
      cumulative probability of death for patients with definite HF was 15.9 times
      higher in men and 14.7 times higher in women in comparison with the UK
      population. CONCLUSION: The diagnosis of HF by a GP successfully identifies
      patients at high risk of death, comparable to patients with HF identified by
      cardiologists on the basis of defined diagnostic criteria. HF is common in the
      general population, increases sharply with age, and has a poor prognosis.

PMID- 15718169
TI  - Diagnosis and assessment of the heart failure patient: the cornerstone of
      effective management.
AB  - Heart Failure is a syndrome describing a pathophysiological state with diverse
      etiologies. Providing an adequate mechanistic definition is difficult. The
      current guidelines from the European Society of Cardiology define the diagnosis
      of heart failure based on three criteria. Patients should have symptoms
      compatible with heart failure at rest or on exercise. There should be objective
      evidence of cardiac dysfunction at rest. In doubtful cases, there should be a
      favourable response following therapy for heart failure. The term diagnosis
      derives from the Greek words "dia" and "nosi" meaning "through knowledge". It
      implies that a conclusion is drawn describing the patient's current status based
      on the available information. This information is commonly based on the symptoms,
      history, findings at physical examination, results from laboratory tests, and the
      results from various non-invasive and invasive special examinations. Diagnostic
      precision is crucial in deciding treatment strategy and this task presents a
      continuous academic and clinical challenge. Ultimately, the clinical diagnosis of
      heart failure is based on all the information available to the physicians. No
      single investigation is specific for this clinical syndrome and management
      strategies attempt to modify the underlying mechanisms in order to alleviate
      symptoms and improve survival.

PMID- 15718170
TI  - Frequent non-cardiac comorbidities in patients with chronic heart failure.
AB  - Heart failure (HF) in elderly patients is associated with more diffuse symptoms
      and signs due to the presence of other noncardiac comorbidities. This can cause
      difficulties in assessing the correct diagnosis and initiating appropriate
      therapy. The four most frequently occurring noncardiac comorbidities and
      therapies used to treat them are discussed in the present paper. Hypertension is
      an important precursor of HF, and is still the most common risk factor for HF in
      the general population. About 50% of patients with untreated hypertension will
      develop HF. Pressure overload leads to the development of left ventricular
      hypertrophy (LVH) and diastolic dysfunction. Diabetes, which occurs in about 20
      30% of patients with HF, is an important comorbidity resulting in morphological
      and metabolic disturbances affecting myocardial blood flow and hormonal
      regulation leading to a poor outcome and necessitating aggressive conventional
      treatment. Chronic obstructive pulmonary disease (COPD), occurs in approximately
      20-30% of heart failure patients, and may complicate HF treatment, it is
      therefore important to recognize and treat it effectively. Finally, the early
      detection of anemia, which occurs in 20-30% of HF patients, is important since it
      is associated with functional impairment and increased mortality and morbidity.
      Combined treatment with erythropoietin and intravenous iron has shown beneficial
      effects on clinical symptoms and morbidity. In conclusion early detection of
      concomitant diseases in patients with HF is important and should be considered
      carefully when initiating therapy.

PMID- 15718171
TI  - Current guidelines in the management of chronic heart failure: practical issues
      in their application to the community population.

PMID- 15718172
TI  - Design of therapy for advanced heart failure.
AB  - Advanced heart failure has been defined as persistent symptoms (NYHA class III
      IV) that limit daily life despite routine therapy with agents of known benefit.
      Although these symptoms can occur both with low and preserved ejection fraction,
      the majority of reported experience is with low ejection fraction, usually <25%.
      For this population with expected one year mortality of 30-50%, over twice the
      mortality of the landmark trials of medical therapy, there is little trial data
      to guide management, which is based largely on collected experience. Once the
      disease has progressed to this stage, therapy focuses upon the twin goals of
      symptom relief and prolongation of survival and is guided according to the
      hemodynamic profiles defined by clinical assessment. As symptoms at this stage
      relate largely to the congestion, therapy is targeted to reduction of elevated
      pulmonary venous and/or systemic venous pressures to near normal levels. The most
      common obstacle to relief of congestion is the increasingly recognized cardio
      renal syndrome, for which both understanding and therapy are currently limited.
      Design of the outpatient regimen for advanced heart failure must be tailored to
      the individual patient. Many patients with advanced heart failure cannot tolerate
      "target" doses of neurohormonal antagonists, and spironolactone should be used
      only when clinical and renal function are sufficiently stable and frequently
      monitored in order to avoid life-threatening hyperkalemia. The clinical benefit
      of bi-ventricular pacing is substantial for the small proportion of patients
      likely to benefit. The vast majority of patients will never be eligible for
      cardiac transplantation or ventricular assist devices. To derive maximal benefit
      from all available therapies, heart failure disease management with collaboration
      of physicians and specialized nurses offers the greatest benefit to the greatest
      number of patients with advanced heart failure.

PMID- 15718173
TI  - Complexity of program and clinical outcomes of heart failure disease management
      incorporating specialist nurse-led heart failure clinics. A meta-regression
      analysis.
AB  - OBJECTIVES: To determine whether a hierarchy of effectiveness exists with respect
      to complexity of published protocols of heart failure (HF) disease management
      (DM) incorporating specialist nurse-led HF clinics. DATA SOURCES AND STUDY
      SELECTION: We searched MEDLINE (1966-November 2004), the Cochrane Library,
      article bibliographies, and contacted experts. Inclusion criteria were random
      allocation of at least 100 patients, specialist HF nurses, HF clinics, and
      readmission as an outcome measure. DATA EXTRACTION: Paired reviewers conducted
      quality assessment, deconstructed and categorized protocols by complexity, and
      extracted results for readmission, mortality, the combined endpoint of mortality
      and hospitalization, HF readmission, and hospital days utilized. DATA SYNTHESIS:
      Six trials were selected (N=949, mean age 73 years [range 62-79], men 58%, LVEF
      34% [27-41], and average follow-up of 8.5 months [3-12]). Compared with usual
      care, the overall relative risk [95% confidence interval] for readmission with
      this strategy was 0.91 [0.72, 1.16], mortality was 0.80 [0.57, 1.06], and the
      combined endpoint of mortality and hospitalization was 0.88 [0.74, 1.04]. We
      observed better outcomes for programs with versus programs without hospital
      discharge planning and immediate post-discharge follow-up; readmission 0.30
      [0.04, 2.60] vs. 1.00 [0.86, 1.17], mortality 0.96 [0.63, 1.47] vs. 0.75 [0.55,
      1.03], the combined endpoint of mortality and hospitalization 0.61 [0.18, 2.02]
      vs. 0.91 [0.80, 1.03], HF readmission 0.09 [0.10, 0.65] vs. 0.65 [0.43, 1.00],
      and hospitalized days utilized per patient -0.26 [-0.49,-0.02] vs. 0.09 [-1.17,
      1.34]. CONCLUSIONS: HF DM with specialist nurse-led HF clinics is a promising
      strategy or effective alternative whose benefit may be optimized by programs with
      a homogeneous structure and components that are delivered with consistency.

PMID- 15718174
TI  - Health care professionals in a heart failure team.
AB  - A heart failure team that treats heart failure patients often faces the challenge
      of managing multiple conditions requiring multiple medications and life style
      changes in an older patient group. A multidisciplinary team approach can
      optimally diagnose, carefully review and prescribe treatment, and educate and
      counsel patients and their families about medication use and life style changes.
      In this paper the possible role of the pharmacist, dietician, physical therapist,
      psychologist, primary care provider and social worker in heart failure management
      is discussed.

PMID- 15718175
TI  - How much responsibility should heart failure nurses take?
AB  - This article examines the emerging role of the heart failure nurse and the
      responsibilities and educational and training requirements surrounding such a
      role. There may be variations in the role and its responsibilities in different
      health care settings. However the principles are similar and include: history
      taking, carrying out clinical assessment and making appropriate decisions about
      patient management within the context of practice. An example of this is nurse
      supervision of adjusting and titration of medication in a clinic setting or in
      the patient's own home. A major challenge to this role is defining the
      limitations and scope of practice. Patients with chronic heart failure (CHF) are
      generally a frail, elderly population, and often have significant other co
      morbidities. They can be on multiple medications and are frequently prescribed
      sub-optimal doses of evidence-based medication. Many patients are not managed by
      specialists, thus creating a huge potential for improved management.

PMID- 15718176
TI  - The crucial role of patient education in heart failure.
AB  - BACKGROUND: Deterioration of heart failure causes and complicates many hospital
      admissions in people aged over 65 years. Frequent readmissions cause an immense
      burden on the individual, the family and the health care system. Heart failure
      management programmes, in which patient education is an important component, have
      been shown to be effective in improving self-care and reducing readmissions. AIM:
      This paper reviews the literature on the education of patients with heart
      failure. The paper addresses the level of knowledge in patients with heart
      failure, barriers to learning, learning needs, educational methods, goals and how
      the effects of patient education can be evaluated. CONCLUSION: Many patients had
      low levels of knowledge and lacked a clear understanding of heart failure and
      self-care. Educational interventions need to be designed specifically for elderly
      patients and need to target barriers to learning such as functional and cognitive
      limitations, misconceptions, low motivation and self-esteem. Health care
      professionals need to be skilled in assessing the requirements and level of
      education given to the individual. New technologies such as computer-based
      education and telemonitoring can be used as tools to improve the education.
      Patient education is an important component of heart failure care and should be
      provided through effective and well-evaluated strategies.

PMID- 15718177
TI  - Management of heart failure in The Netherlands.
AB  - In The Netherlands, the incidence and prevalence of heart failure are rising as
      is the case in most other European countries. Overall, there are 200,000 patients
      with heart failure in The Netherlands and around 25,000 hospitalisations annually
      with a discharge diagnosis of heart failure. Most of these patients are managed
      in primary care, often together with a cardiologist. There is an active guideline
      program in different professional organisations (e.g. general practitioners,
      cardiologists) and in 2002 a collaborative multidisciplinary guideline for
      management of chronic heart failure was developed. However, there is clearly room
      for improvement in the adherence to these guidelines both with regard to the
      diagnosis and the treatment of HF patients. For example, ACE-I and beta-blockers
      are still under-prescribed. In particular, the more severely ill patients seem to
      be under treated. At present, general practitioners and cardiologists differ in
      their views on heart failure, resulting in differences in diagnosis and
      management. In addition to the multidisciplinary guidelines, several other
      initiatives have been developed to improve outcomes in these patients, such as
      rapid access clinics and outpatient heart failure clinics.

PMID- 15718178
TI  - Effects of a nurse-led, clinic and home-based intervention on recurrent hospital
      use in chronic heart failure.
AB  - BACKGROUND: Few studies have examined the potential benefits of specialist nurse
      led programs of care involving home and clinic-based follow-up to optimise the
      post-discharge management of chronic heart failure (CHF). OBJECTIVE: To determine
      the effectiveness of a hybrid program of clinic plus home-based intervention
      (C+HBI) in reducing recurrent hospitalisation in CHF patients. METHODS: CHF
      patients with evidence of left ventricular systolic dysfunction admitted to two
      hospitals in Northern England were assigned to a C+HBI lasting 6 months post
      discharge (n=58) or to usual, post-discharge care (UC: n=48) via a cluster
      randomization protocol. The co-primary endpoints were death or unplanned
      readmission (event-free survival) and rate of recurrent, all-cause readmission
      within 6 months of hospital discharge. RESULTS: During study follow-up, more UC
      patients had an unplanned readmission for any cause (44% vs. 22%: P=0.019, OR
      1.95 95% CI 1.10-3.48) whilst 7 (15%) versus 5 (9%) UC and C+HBI patients,
      respectively, died (P=NS). Overall, 15 (26%) C+HBI versus 21 (44%) UC patients
      experienced a primary endpoint. C+HBI was associated with a non-significant, 45%
      reduction in the risk of death or readmission when adjusting for potential
      confounders (RR 0.55, 95% CI 0.28-1.08: P=0.08). Overall, C+HBI patients
      accumulated significantly fewer unplanned readmissions (15 vs. 45: P<0.01) and
      days of recurrent hospital stay (108 vs. 459 days: P<0.01). C+HBI was also
      associated with greater uptake of beta-blocker therapy (56% vs. 18%: P<0.001) and
      adherence to Na restrictions (P<0.05) during 6-month follow-up. CONCLUSION: This
      is the first randomised study to specifically examine the impact of a hybrid,
      C+HBI program of care on hospital utilisation in patients with CHF. Its
      beneficial effects on recurrent readmission and event-free survival are
      consistent with those applying either a home or clinic-based approach.

PMID- 15718179
TI  - Heart failure care in a hospital unit: a comparison of standard 3-month and
      extended 6-month programs.
AB  - BACKGROUND: We have previously shown that a structured in-hospital and outpatient
      heart failure (HF) program reduces clinical events over a 3-month period
      following hospital discharge. AIMS: This prospective randomized controlled study
      examines the additional benefits of extending the standard 3-month HF program to
      6 months on death and readmission over a 2-year follow-up period. METHODS: Of 161
      patients admitted with NYHA class IV HF who completed the standard 3-month HF
      program, 130 consenting patients (mean age 69.9+/-12.2 years, 65% male) were
      randomized to the extended 6-month HF program (EP; n=62) or standard care (SP;
      n=68). The primary endpoint was death and/or unplanned rehospitalization for HF
      at 2 years postrandomization. RESULTS: In the 2-year follow-up period, there were
      eight people with unplanned hospitalizations for HF and 16 deaths in the EP group
      (event rate 38.7%) compared to seven people with unplanned HF readmissions and 14
      deaths in the SP group (event rate 30.9%, p=0.348 versus EP). Kaplan-Meier
      survival analysis demonstrated no difference in outcome between standard and
      extended program (p=0.315). There were no differences between the groups in terms
      of unscheduled clinic visits or non-HF-related readmissions in the 2-year follow
      up period. CONCLUSIONS: There is no measured clinical advantage in terms of death
      and/or HF readmission in extending a structured hospital-based disease management
      program for HF beyond 3 months postdischarge. However, it appears that patients
      continue to need access to the service to help abort clinical deteriorations, and
      this may have implication for the optimal organisation of such programs.

PMID- 15718180
TI  - Patients with heart failure in primary health care: effects of a nurse-led
      intervention on health-related quality of life and depression.
AB  - AIMS: To determine the effects of a nurse-led intervention designed to improve
      self-management of patients with heart failure in a primary health care setting
      regarding health-related quality of life and depression. METHODS: Patients at
      eight primary health care centres were screened by the Diagnosis Related Groups
      registry for the diagnosis of heart failure and eligibility for a cluster
      randomised study. A total of 153 patients were included (n=78 in the intervention
      group, 54% males, mean age 79 years, 59% in New York Heart Association class III
      IV). The intervention involved patient and family education about heart failure
      and self-management and monthly telephone follow-up during 12 months by a primary
      health care nurse. RESULTS: The effects of the nurse-led intervention were
      limited. Significant differences were found in the physical dimension measured by
      the SF-36 health survey, and in depression measured by the Zung Self-rating
      Depression Scale. In comparison within groups at the 3 and 12-month follow-up,
      the intervention group significantly maintained their health-related quality of
      life measured by the SF-36 health survey, and their experience of depression
      measured by the Zung Self-rating Depression Scale to a greater extent than in the
      control group, especially among women. CONCLUSION: A nurse-led intervention
      directed toward patients with heart failure in a primary health care setting
      resulted in limited effects between the groups, although the physical and mental
      status were retained during 12 months of follow-up to a greater extent than in
      the control group.

PMID- 15718181
TI  - Success of a multidisciplinary heart failure clinic for initiation and up
      titration of key therapeutic agents.
AB  - BACKGROUND: Heart failure has a poor prognosis, yet drugs known to improve
      outcomes are either not prescribed, or prescribed at sub-therapeutic doses. The
      National Service Framework (NSF) for coronary heart disease recommended
      specialist heart failure clinics to address this problem but their efficacy has
      not been evaluated. OBJECTIVES: To determine the effectiveness of a protocol
      driven heart failure clinic staffed by nurse and pharmacist specialists for
      improving symptoms and optimising treatment with key therapeutic agents, without
      adversely affecting renal function. RESULTS: Of the 234 patients with at least
      one follow-up visit, 127 (57%) were receiving none or only one key therapeutic
      agent when first seen, this was reduced to 25 patients (11%) at most recent
      follow-up. The improvement in prescription rates was accompanied by significant
      up-titration of dose, the proportion of patients on "medium" or "high" doses
      rising from 43 (18%) to 134 (57%) for beta-blockers, and from 129 (55%) to 201
      (86%) for ACE-inhibitors/angiotensin receptor blockers. Clinical improvement was
      reflected in reductions in patients with NYHA functional classes III and IV (93
      (40%) to 53 (23%)), and in patients with moderate or severe symptoms. Significant
      reductions in alcohol consumption and cigarette smoking were recorded. Up
      titration of treatment was associated with reductions in heart rate and systolic
      blood pressure; increases in serum potassium and creatinine concentrations were
      small. CONCLUSION: In a heart failure clinic staffed by nurse and pharmacist
      specialists, it is possible to achieve target doses of key therapeutic agents and
      improve symptoms without adversely affecting electrolytes or renal function.

PMID- 15718182
TI  - Randomised controlled trial of cardiac rehabilitation in elderly patients with
      heart failure.
AB  - BACKGROUND: Heart failure, a condition predominantly affecting the elderly,
      represents an ever-increasing clinical and financial burden for the NHS. Cardiac
      rehabilitation, a service that incorporates patient education, exercise training
      and lifestyle modification, requires further evaluation in heart failure
      management. AIM: The aim of this study was to determine whether a cardiac
      rehabilitation programme improved on the outcomes of an outpatient heart failure
      clinic (standard care) for patients, over 60 years of age, with chronic heart
      failure. METHODS: Two hundred patients (60-89 years, 66% male) with New York
      Heart Association (NYHA) II or III heart failure confirmed by echocardiography
      were randomised. Both standard care and experimental groups attended clinic with
      a cardiologist and specialist nurse every 8 weeks. Interventions included
      exercise prescription, education, dietetics, occupational therapy and
      psychosocial counselling. The main outcome measures were functional status (NYHA,
      6-min walk), health-related quality of life (MLHF and EuroQol) and hospital
      admissions. RESULTS: There were significant improvements in MLHF and EuroQol
      scores, NYHA classification and 6-min walking distance (meters) at 24 weeks
      between the groups (p<0.001). The experimental group had fewer admissions (11 vs.
      33, p<0.01) and spent fewer days in hospital (41 vs. 187, p<0.001). CONCLUSIONS:
      Cardiac rehabilitation, already widely established in the UK, offers an effective
      model of care for older patients with heart failure.

PMID- 15718183
TI  - Health-related quality of life in patients with congestive heart failure.
AB  - BACKGROUND: Despite abundant evidence attesting to poor physical, psychological
      and social functioning of congestive heart failure (CHF) patients, little is
      known about the impact of the disease itself on health-related quality of life
      (HRQL). Most previous work has focused on general quality of life issues rather
      than specifically on the impact of CHF on HRQL. AIM: To identify the significant
      demographic, clinical and psychosocial factors associated with HRQL in patients
      with CHF. METHODS: A total of 227 CHF patients were recruited from the medical
      unit of a general hospital in Hong Kong. Cross-sectional data on HRQL, functional
      status, psychological state, social support and health perception were obtained
      from each patient and clinical data were obtained from hospital records. RESULTS:
      In hierarchical regression analysis, psychological distress, poor health
      perception, higher NYHA grading and lower education level were identified as the
      significant factors associated with poorer HRQL. These correlates in total
      explained 52% of the variance for the HRQL scores. Among these correlates,
      psychological distress and NYHA grading demonstrated the greatest effect on HRQL
      scores. CONCLUSION: The findings highlight the significance of addressing the
      psychological and functional health of CHF patients. Assisting these patients to
      cultivate a positive attitude towards their own health status is also an
      important treatment goal.

PMID- 15718184
TI  - Financial aspects of heart failure programs of care.
AB  - As suggested by studies that have examined the economic burden imposed by heart
      failure and, more specifically where the greatest expenditure occurs, the key to
      cost-effectively minimising the impact of a sustained heart failure epidemic is
      to minimise recurrent hospital use--even at the expense of increasing levels of
      community-based care and prescribed pharmacotherapy. This paper examines the
      potential cost-benefits of applying specialist heart failure programs of care and
      the range of financial issues that need to be considered when establishing a
      formal heart failure service.

PMID- 15718185
TI  - The facts on nurses and smoking.

PMID- 15718186
TI  - What does it mean to live with a congenital heart disease? A qualitative study on
      the lived experiences of adult patients.
AB  - BACKGROUND: Adults with congenital heart disease constitute a relatively new and
      continuously growing patient population. In addition to medical problems,
      patients perceive specific psychosocial concerns that influence their lived
      experiences and quality of life. AIM: This study aimed to explore the lived
      experiences of adult congenital heart disease patients. METHODS: Unstructured, in
      depth interviews were performed with 12 patients, aged between 25 and 40 years
      and suffering from moderate or severe heart defect (tetralogy of Fallot,
      transposition of the great arteries). Interviews were tape recorded and
      transcribed verbatim. Data were analyzed using Grounded Theory procedures.
      RESULTS: Feeling different was the central theme of the patients' lived
      experience, as they are faced with physical limitations and visible signs due to
      the heart defect. The experienced discordance between their world and healthy
      individuals' world implies that patients struggle constantly with themselves and
      with their environment to be accepted as normal. The feeling of being different
      was influenced by attitudes of the environment, health care, and patient's
      personality. Moreover, it determined the perceived impact of the disease on the
      patient's daily life. CONCLUSION: This study shows that normalisation is the most
      important process when dealing with patients suffering from a congenital heart
      disease.

PMID- 15718187
TI  - For better and for worse: Quality of life impaired in HF patients as well as in
      their partners.
AB  - BACKGROUND: Quality of Life (QOL) is known to be impaired in patients with Heart
      Failure (HF). The involvement of a key person, most often the spouse, enables the
      HF patient to manage the medical regimen and therefore to sustain Quality of Life
      (QOL). Yet little is known on the impact of caring for an HF patient on the QOL
      of the caregiving partner. This study aims to explore the QOL of partners of HF
      patients compared to the QOL of the patients. METHODS: The study population
      consisted of 38 couples of hospitalized HF patients and their partners. The
      Cantril Ladder of Life was used to rate QOL during hospitalization, with regard
      to the month prior to hospitalization and as projected 3 years in the future.
      Demographic and clinical variables were collected by patient interview and chart
      review. RESULTS: On a scale from 0-10, QOL scores of partners varied from 5.9 to
      6.4. At some point the QOL score of partners was even lower than the QOL scores
      of HF patients. In the month prior to hospital admission the QOL of partners was
      significantly higher in comparison to the QOL of HF patients (6.1 vs. 4.9,
      respectively). However, this reversed during hospital admission, with QOL scores
      of partners being significantly lower compared to QOL scores of HF patients (5.9
      vs. 6.8, respectively), even after correcting for age and gender. CONCLUSION: In
      our study the QOL of partners of HF patients was low. Whether this is explicitly
      due to having to live with a HF patient is not clear. Further research on what
      partners actually do and the relationship between being a caregiver and QOL is
      necessary in order to support these partners in giving optimal care and support.

PMID- 15718188
TI  - Cardiac nursing: achieving competent practitioners.
AB  - This paper describes how competency statements were integrated into an academic
      framework to provide a transparent yet flexible career pathway for the nurse
      working in acute cardiac care. Nurses are expanding and developing their roles
      and use wide ranging skills and knowledge to care for patients. Additionally,
      models of care delivery are changing and patients are cared for in a variety of
      settings. Where evidence exists, these models demonstrate improvement in the
      provision and quality of services and contribute to improved quality of life,
      maximise medication and therapy and reduce waiting times for investigations.
      However, whilst many studies have demonstrated benefit, translating these results
      into routine practice requires skilled nurses who are "fit for purpose," and to
      support this, professional competencies can be used to measure competence in
      practice whilst informing educational initiatives. This paper outlines the
      development of competency statements that identify the knowledge and skills
      required for safe, effective and competent care and direct the cardiac nurse
      acquire skills and knowledge in a focused and coherent way.

PMID- 15718190
TI  - Women's interpretation of their coronary heart disease symptoms.
AB  - BACKGROUND: Men and women are known to delay in seeking medical attention when
      experiencing acute cardiac symptoms. However, women are more likely to have had
      chronic undifferentiated symptoms prior to an acute episode and then when
      experiencing an acute episode delay longer than do men. Studies have shown once
      women do present they tend to be further along the disease trajectory than men.
      AIMS: The aim of this study was to explore women's own interpretation of the
      presenting symptoms they experienced. METHODS: Twenty-nine women consented to
      take part in semi-structured interviews that focussed on their experience of
      coronary heart disease (CHD). The women's narrative around the initial disruption
      of their illness was analysed focusing on routine and reconstructed forms of
      narration. RESULTS: The results showed that many failed to recognise and act on
      their symptoms. Most only sought medical attention after family or friends
      intervened. None of the women had seen themselves at risk of developing coronary
      heart disease despite many have a strong family history. CONCLUSION: The women's
      early symptoms of coronary heart disease were often undifferentiated and
      difficult to interpret by the women themselves. There is a need for further
      research to understand and recognise early symptoms of coronary heart disease in
      women. This will allow women and health professionals to assess risk and identify
      women with coronary heart disease early on in their disease trajectory so therapy
      to prevent the morbidity associated with coronary heart disease and acute life
      threatening episodes will be reduced.

PMID- 15718189
TI  - Setting up and auditing guideline- and evidence-based cardiac rehabilitation.
AB  - BACKGROUND: Rehabilitation is available to only a minority of post-myocardial
      infarction (MI) patients and is of variable quality. Guidelines now recommend
      individualised care delivered by hospital, primary care and community services,
      but there is little evidence of the feasibility, acceptability or effectiveness
      of this approach. AIMS: To demonstrate the feasibility of guideline-based
      rehabilitation, to audit delivery and outcome and to identify problems. METHODS:
      A four-phase stepped programme for post-MI patients was developed based on
      individualised in-hospital care and aftercare from a menu of options. Delivery
      involved co-ordination between hospital services, primary care and community
      services. Self-report audit data were collected in hospital and at 3 months post
      discharge by postal questionnaire and telephone calls. Clinical information was
      recorded from hospital, telephone and outpatient contacts. Delivery of care to
      patients receiving interventions was recorded. RESULTS: It was possible to
      negotiate individualized plans for all patients and to monitor progress for 3
      months after discharge. The rehabilitation team achieved high rates of delivery
      of agreed interventions, considerably better than delivery by primary care.
      Problems largely related to difficulties and failures in communication. Patients
      with major social or psychological difficulties were the most difficult to treat.
      CONCLUSION: Guideline-based rehabilitation is feasible, but there is a need to
      improve the coordination of delivery of later steps of care and also to refine
      specialist interventions.

PMID- 15718191
TI  - A qualitative study of the information needs of acute myocardial infarction
      patients, and their preferences for follow-up contact after discharge.
AB  - BACKGROUND: Several studies have claimed that patients have unmet information
      needs after discharge following acute myocardial infarction (AMI). Our overall
      goal is to develop a post-discharge nursing intervention program to provide
      patients with appropriate information and support in contexts where existing
      follow-up services are poorly developed. AIMS: To explore the information needs
      of inpatients with AMI and their preferences for follow-up contact after
      discharge from hospital. METHODS: Fourteen AMI patients aged 42-69 years
      participated in one of three focus groups, held between 3 and 5 months after
      their discharge. RESULTS AND CONCLUSIONS: The findings are grouped into three
      themes corresponding to the major topics in the interview guide: the hospital
      stay, coming home, and patients' follow-up preferences. The data support the
      findings of previous studies that there is a systemic failure to meet patients'
      in-hospital and post-discharge information needs. Most importantly, our
      participants' follow-up preferences favoured open telephone lines and telephone
      follow-up. The results of this study provide some of the knowledge that is
      necessary to improve patient information and support following AMI.

PMID- 15718192
TI  - Is "fat free" good for me? A panel study of television viewing and children's
      nutritional knowledge and reasoning.
AB  - The family diet is influenced by children's attitudes toward food, which in turn
      are influenced by television. In a panel study involving 134 children in 1st to
      3rd grade, television viewing, nutritional knowledge, and nutritional reasoning
      were measured 6 weeks apart. Television viewing predicted subsequent decrements
      in nutritional knowledge and reasoning, but these findings were significant only
      for foods that tend to be heavily marketed as weight-loss aids. Television's
      framing of diet foods may confuse children by equating weight-loss benefits with
      nutritional benefits.

PMID- 15718193
TI  - Effects of coping information and value affirmation on responses to a perceived
      health threat.
AB  - In this study, we examined the effects of coping information and self-affirmation
      on an individual's response to threatening health information. A total of 202
      women college students read an essay containing threatening information about
      breast cancer. The essay described their population as being at risk for breast
      cancer and included both pictures of cancerous breasts and vivid descriptions of
      chemotherapy treatments. Participants were randomized into either the low
      affirmation condition or the high-affirmation condition when they first arrived.
      In addition, half of the participants were randomly assigned to receive coping
      information that described breast self-examinations as an effective method of
      detecting breast cancer and focused on the importance of early detection.
      Participants who received coping information scored lower on maladaptive
      behaviors (avoidance, hopelessness, religiosity), suggesting that coping
      information plays a role in decreasing maladaptive behaviors. No significant
      differences were found between the low-affirmation and high-affirmation
      conditions. Supplemental analyses indicated that vicarious exposure to breast
      cancer (having a friend, relative, or mother diagnosed with breast cancer)
      affected how individuals interpret threatening health information. Participants
      with previous exposure scored higher on the adaptive coping modes (behavioral
      intentions, rational problem solving) and 1 maladaptive coping mode (religiosity)
      when compared to individuals without previous exposure. In addition, participants
      in the high-affirmation condition with previous exposure scored higher on
      avoidance and hopelessness than those without previous exposure. The results
      suggest that coping information and previous exposure are factors that need to be
      considered when presenting threatening health information.

PMID- 15718194
TI  - Metaphor in formative evaluation and message design: an application to
      relationships and alcohol use.
AB  - Conceptual metaphor analysis offers an underutilized method for formative
      evaluation. Using the domain of relationships and alcohol use, the viability of
      this technique was demonstrated through an analysis of 22 focus group
      transcripts, exploratory and confirmatory factor analyses, and a message
      perceptions experiment. The studies revealed a number of conceptual metaphors
      college students possess and utilize to interpret messages regarding
      relationships, sexuality, and effects of alcohol use. In light of the results,
      strategies for message design are suggested.

PMID- 15718195
TI  - The importance of precision in language: communication research and (so-called)
      alternative medicine.
AB  - Holistic (alternative) medical systems and techniques are used so extensively in
      the United States, it necessitates that health communication researchers include
      these practices in the corpus of literature. In this essay, I interrogate the
      terminology that is used to describe holistic medical practice in the United
      States. There are important distinctions between the use of such terms as
      holistic and alternative by virtue of the way that the medical systems themselves
      are constructed and evaluated. I advocate that the terms biomedical and holistic
      be used to refer to explanatory models and offer additional suggestions for
      language use throughout the research process. In the article, I conclude with a
      discussion of the consequences of discursive choices for research and for health
      care consumers.

PMID- 15718196
TI  - Hope, disclosure, and control in the neonatal intensive care unit.
AB  - The parents of critically ill newborns who have been admitted to a neonatal
      intensive care unit (NICU) generally face several challenges. Included in these
      challenges is the possibility of having access to information and a certain level
      of disclosure about the diagnosis, treatment options, and prognosis for their
      newborn. A related challenge is the ability to have some control over the care of
      their newborn. In this article, I (first author) share my own experiences of
      having a child admitted to an NICU, and I discuss how a lack of disclosure
      affected the decision making and involvement I had in my child's care and
      hindered my ability to find hope. A loss of hope can both contribute to a sense
      of powerlessness and exacerbate the negative aspects of these NICU experiences. I
      argue that when health care providers offer parents the disclosure they want and
      need, as well as a certain amount of control over the care of their child while
      in the NICU, the ability of parents to find hope will be increased, and they will
      be better able to cope successfully in the NICU environment.

PMID- 15718197
TI  - Bibliography.

PMID- 15718199
TI  - Cytoplasmic changes and developmental competence of bovine oocytes cryopreserved
      without cumulus cells.
AB  - The cryopreservation of female gametes is still an open problem because of their
      structural sensitivity to the cooling-and-freezing process and to the exposure to
      cryoprotectants. The present work was aimed to study the effect of vitrification
      on immature bovine oocytes freed of cumulus cell investment before freezing. To
      verify the feasibility and efficiency of denuded oocyte (DO) cryopreservation,
      the cytoplasmic alterations eventually induced either by cell removal or by the
      vitrification process were analyzed. In particular, the migration of cortical
      granules and Ca++ localization were studied. In addition, the localization and
      distribution of microtubules and microfilaments in immature fresh and vitrified
      DOs were evaluated. Finally, to establish whether the removal of cumulus cells
      influenced developmental competence, DOs were thawed after vitrification, matured
      in vitro and fertilized; then presumptive zygotes were cultured to reach the
      blastocyst stage. The results indicate that mechanical removal of cumulus cells
      from immature bovine oocytes does not affect their maturation competence but
      reduces the blastocyst rate when compared with intact cumulus oocyte complexes
      (COCs). The findings indicate further that the vitrification process induces
      changes of cytoplasmic components. However, the composition of the manipulation
      medium used to remove cumulus cells plays a crucial role in reducing the injuries
      caused by cryopreservation in both cytoplasmic and nuclear compartments. In fact,
      the presence of serum exerts a sort of protection, significantly improving both
      oocyte maturation and blastocyst rates. In conclusion, we demonstrate that
      denuded immature oocytes can be vitrified after cumulus cells removal and
      successfully develop up, after thawing, to the blastocyst stage, following in
      vitro maturation and fertilization.

PMID- 15718200
TI  - Exposure of pig oocytes to PCBs during in vitro maturation: effects on
      developmental competence, cytoplasmic remodelling and communications with cumulus
      cells.
AB  - Polychlorinated biphenyls (PCBs) are one of the most persistent and widespread
      groups of endocrine disrupting compounds in the ecosystem. These substances are
      present in sewage sludge that is spread in increasing amounts on arable land and
      pasture as fertilizer, and are ingested by farm animals with food and drinking
      water. This study investigated the effect of different PCB concentrations on pig
      oocyte in vitro maturation and developmental competence as well as examined the
      possible mechanisms involved. A concentration ranging from 0 to 1 mg/mL of
      Aroclor 1254 (A1254), a pool of more than 60 PCB congeners, was added to the
      maturation medium, as its composition is considered environmentally relevant.
      A1254 had no effect on maturation of pig oocytes and on the number of oocytes
      that cleaved following parthenogenetic activation at any of the doses tested. By
      contrast, a significant decrease in the number of zygotes that developed to
      blastocyst stage became evident at a concentration of 10 ng/mL. The number of
      blastocysts obtained decreased significantly, and in a dose response manner with
      higher concentrations. Exposure to PCBs altered mitochondria relocation during
      maturation and this was associated with the lack of a cytoplasmic microtubule
      network. No effect on mitochondria activity was observed. A1254 exposure also
      perturbed gap-junction mediated communications between oocytes and cumulus cells.
      In conclusion, PCB exposure of pig oocytes during in vitro maturation
      significantly decreased oocyte developmental competence, altered both their
      cytoplasmic remodelling and the communication with the somatic compartment. These
      data indicated that accumulation of PCBs in the pig organism may have a
      detrimental effect on the reproductive efficiency in this species.

PMID- 15718201
TI  - Myosin heavy chain 2B isoform is expressed in specialized eye muscles but not in
      trunk and limb muscles of cattle.
AB  - Myosin heavy chain isoforms (MHC) of adult skeletal muscles are codified by four
      genes named: slow, or type 1, and fast types 2A, 2X and 2B. The slow, 2A and 2X
      isoforms have been found expressed in all mammalian species studied so far
      whereas there is a large inter-species variability in the expression of MHC-2B.
      In this study histochemistry (m-ATPase), immunohistochemistry with the use of
      specific monoclonal antibodies and RT-PCR were combined together to assess
      whether the MHC-2B gene is expressed in bovine muscles. ATPase staining and RT
      PCR experiments showed that three MHC isoforms (1, 2A, 2X) were expressed in
      trunk and limb muscles. Slow or type 1 expression was confirmed using a specific
      antibody (BA-F8) whereas the detection of fast MHC isoforms were validate by
      means of BF-35 antibody although not by the SC-71 antibody. MHC-2B was absent in
      limb and trunk muscles, but was present in specialized eye muscles (rectus
      lateralis and retractor bulbi) as consistently showed by RT-PCR and reactivity
      with a specific antibody (BF-F3). Interestingly, a cardiac isoform, MHC-a-cardiac
      was found to be expressed not only in extraocular muscles but also in masticatory
      muscles as masseter.

PMID- 15718202
TI  - The vasotocinergic system in the hypothalamus and limbic region of the budgerigar
      (Melopsittacus undulatus).
AB  - We report a morphological and biochemical analysis on the presence, distribution
      and quantification of vasotocin in the hypothalamus and limbic region of the
      budgerigar Melopsittacus undulatus, using immunohistochemistry on serial sections
      and competitive enzyme linked immunoadsorbent assay measurements on tissue
      extracts. Analysis of the sections showed large vasotocin-immunoreactive neurons
      in three main regions of the diencephalon, of both male and female specimens.
      Vasotocinergic cell bodies were located in the ventral and lateral areas of the
      hypothalamus, dorsal to the lateral thalamus and medial to the nucleus
      geniculatus lateralis. Immunoreactive neurons were placed also periventricularly,
      close to the walls of the third ventricle, at the level of the magnocellular
      paraventricular nucleus. Well evident bundles of immunoreactive fibers were
      placed ventral to the anterior commissure in the same regions of the hypothalamus
      and thalamus where vasotocinergic perikarya are localized. Fibers were identified
      close to the third ventricle, and in the lateral hypothalamic area along the
      lateral forebrain bundle. In contrast to what reported for other oscine and non
      oscine avian species, we were not able to identify immunopositive neurons in any
      region above the anterior commissure, or detect relevant differences on the
      distribution of the vasotocin immmunoreactivity between sexes. Competitive enzyme
      linked immunoadsorption assay and image analysis of the extension of
      immunoreactivity in the tissue sections were consistent with the qualitative
      observations and indicated that there is no statistically significant dimorphism
      in the content of vasotocin or in the location and distribution of vasotocinergic
      elements in the investigated areas of male and female parrot brains.

PMID- 15718203
TI  - Immunohistochemical detection of [corrected] TrkB in the enteric nervous system
      of the small intestine in pigeon (Columba livia).
AB  - The presence and cell localization of TrkB, the main receptor for the
      neurotrophins (NTs), was investigated immunohistochemically in the small
      intestine of adult pigeons, with special reference to the enteric nervous system
      (ENS). Several neuronal (neurofilament proteins and PGP 9.5) and glial cell (S100
      protein) markers were studied in parallel. TrkB immunoreactivity (TrkB-IR) was
      found to be restricted to immunohistochemically-identified glial cells present in
      the enteric plexuses, and to Schwann cells forming the perivascular plexus. Also,
      TrkB-IR was detected in enterochromaffin cells and in unidentified dendritic
      cells within the gut-associated lymphoid tissue. The present results demonstrate
      that as for mammals, TrkB in the ENS is restricted to the glial cells. The
      possible function of the TrkB ligands, however, remains to be established.

PMID- 15718204
TI  - Development of the Senegal sole, Solea senegalensis forebrain.
AB  - The present paper deals with the ontogeny of the forebrain of the flatfish
      Senegal sole, Solea senegalensis, through different developmental stages before
      and after to metamorphosis. A first approach was made by conventional
      histological techniques, which allowed the determination of the main ontogenetic
      events. A second approach was to analyze the proliferation zones (PZ) during
      development and their locations, as well as the relation between them and the
      telencephalic asymmetry of the Senegal sole. The results show that before
      metamorphosis the Senegal sole goes through a fast development. The pituitary is
      visible 1 day after hatching (DAH), the inferior lobes of the hypothalamus appear
      3 DAH, and the olfactory bulb and the differentiation between telencephalon and
      diencephalon are present around 4 DAH. In addition, by applying proliferating
      cell nuclear antigen (PCNA) immunohistochemistry by means of a monoclonal
      antibody against the PCNA and ABC complex, we were able to determine the PZs in
      the forebrain of pre- and post- metamorphic specimens. Although in both cases the
      PZs were similar, in premetamorphic animals they were thicker. However, PZs were
      observed in the pallium and subpallium, preoptic region, pretectum, epithalamus,
      dorsal and ventral thalamus, posterior tuberculum and hypothalamus. In all cases
      the PZs, mainly focusing on the telencephalon, were symmetrical in both
      hemispheres.

PMID- 15718206
TI  - Histochemical analysis of glycoconjugates in the eccrine glands of the raccoon
      digital pads.
AB  - The distribution and selectivity of complex carbohydrates in the eccrine glands
      of the digital pads in the North American raccoon (Procyon lotor) were studied
      using light and electron microscopic histochemical methods, particularly lectin
      histochemistry. In the eccrine glands, the dark cells exhibited neutral and
      acidic glycoconjugates with different saccharide residues (alpha-L-fucose, beta-D
      galactose, beta-N-acetyl-D-glucosamine and N-acetyl-neuraminic acid); the clear
      cells contained numerous glycogen particles and showed a distinct reaction of
      alpha-L-fucose. The presence of complex carbohydrates with various terminal
      sugars was evident in the excretory duct cells. In addition, beta-D-galactose and
      N-acetyl-neuraminic acid residues were mainly observed in the luminal secretion.
      The glycoconjugates produced by the eccrine glands of the raccoon digital pads
      may protect the epidermis against physical damage or microbial contamination. In
      this way, the normal functioning of the sensory apparatus of the foot pads is
      ensured.

PMID- 15718205
TI  - MPTP-induced increase in c-Fos- and c-Jun-like immunoreactivity in the monkey
      cerebellum.
AB  - The transcription factors c-Fos and c-Jun have been described to be overexpressed
      following many pathological stimuli, but whether they are required for
      neurodegeneration or neuroprotection is still open. In the present report, we
      analyzed the role of c-Fos and c-Jun proteins in Purkinje cell degeneration
      caused by the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in
      the monkey cerebellum, and determined the neuroprotective effect of the
      antioxidant drug a-dihydroergocryptine (DHEC), whose prior and simultaneous
      administration reduced the MPTP-induced neuronal loss in the substantia nigra.
      Immunocytochemistry for c-Fos- and c-Jun-like proteins showed persistent
      increased staining in Purkinje cells of MPTP-treated monkeys. The staining was
      greatly reduced in animals receiving DHEC. Similar results were observed in white
      matter glial cells after immunoreaction for c-Fos. The results suggest that, at
      least as far as the cerebellum is concerned, the increase in c-Fos and c-Jun
      expression correlate with cell damage, rather than with preservation.

PMID- 15718207
TI  - Distribution of sialoglycoconjugates in the oviductal isthmus of the horse during
      anoestrus, oestrus and pregnancy: a lectin histochemistry study.
AB  - The distribution of sialic acid residues as well as other glycosidic sugars has
      been investigated in the horse oviductal isthmus during anoestrus, oestrus and
      pregnancy by means of lectin and pre-lectin methods. Ciliated cells and non
      ciliated (secretory) cells exhibited different lectin binding profiles that were
      found to change during the investigated stages. Ciliated cells did not show any
      reactivity in the basal cytoplasm, while the supra-nuclear cytoplasm displayed a
      few of oligosaccharides with terminal and internal alphamannose (Man) and/or
      alphaglucose (Glc) during oestrus and pregnancy and a moderate presence of
      oligosaccharides terminating in alphafucose (Fuc) during oestrus; cilia exhibited
      a more complex glycoconjugate pattern for the presence of oligosaccharides
      terminating in N-acetylgalactosamine (GalNAc), GalNAcalpha1,3
      GalNAcalpha1,3galactose(Gal)beta1,4Galbeta1,4N-acetylglucosamine(GlcNAc), Fuc,
      sialic acid (Neu5Ac)-aGalNAc belonging or not to the GalNAca1,3GalNAca1,3 Galb1,4
      Galb1, 4GlcNAc sequence, and. alphaGalNAc and Neu5Aca 2,6Gal/GalNAc increased
      during oestrus. Cilia displayed terminal Galbeta1,3 GalNAc in pregnancy, terminal
      alphaGal in anoestrus and pregnancy and terminal or internal D-GlcNAc during
      anoestrus and pregnancy, respectively. The whole cytoplasm of non-ciliated cells
      showed oligosaccharides terminating with alphaGalNAc, Neu5Aca2,6Gal/GalNAc,
      Neu5Ac GalNAca 1,3GalNAcalpha1,3Galbeta1,4Galbeta1,4GlcNAc during the
      investigated stages, as well as GlcNAc in anoestrus and pregnancy. The supra
      nuclear zone of non-ciliated cells exhibited oligosaccharides with terminal
      Galbeta1,4GlcNAc and internal Man during oestrus and pregnancy as well as
      terminal alphaGal and Fuc in oestrus and Neu5Ac-Galbeta1,3GalNAc in pregnancy.
      The luminal surface of non-ciliated cells showed glycans terminating with
      alphaGalNAc and/or Neu5Ac GalNAcalpha1,3 GalNAcalpha1,3Galbeta1,4Galbeta1,4GlcNAc
      in all specimens, oligosaccharides with terminal Galbeta1,4GlcNAc and internal
      Man during oestrus and pregnancy, Neu5Ac alpha2,6Gal/GalNAc in anoestrus and
      oestrus, and glycans terminating with Galbeta1,3GalNAc, Neu5A acalpha2,3
      Galbeta1, 4GlcNac, Neu5ac-Galbeta1,3GalNAc, Neu5Ac-Galbeta1,4 GlcNAc in
      pregnancy. These findings show the presence of sialoglycoconjugates in the
      oviductal isthmus of the mare as well as the existence of great modifications in
      the glycoconjugates linked to different physiological conditions.

PMID- 15718208
TI  - Histological and immunohistochemical investigation on ovarian development and
      plasma estradiol levels in the swordfish (Xiphias gladius L.).
AB  - The paper reports a histological and immunohistochemical description of oocyte
      growth and ultrastructural aspects of zona radiata (ZR) formation as well as the
      relationship between plasma estradiol-17beta, (E2) levels and ovarian development
      in swordfish (Xiphias gladius L.) from the Mediterranean Sea. Ovaries were
      inactive during March to mid April; maturation occurred during late April to June
      and spawning in June and July. Zona radiata formation starts, as Pas positive
      material, in oocytes at the lipid stage. In this stage a deposit of electrondense
      material between oolemma and follicular cells appears. In the cortical alveoli
      stage and through the early vitellogenic stage, the deposition of a moderately
      electrondense material occurred on the inner side of the ZR. Finally, in late
      vitellogenic oocytes a third layer, made of microfibrillar material, appeared.
      The immunohistochemical analyses revealed that the initial internalisation of
      hepatic zona radiata proteins (Zrp) in the swordfish oocyte starts before the
      uptake of vitellogenin (Vtg) and that it is associated with the low
      previtellogenic E2 plasma levels, while a significant E2 increase in plasma is
      associated with the beginning of Vtg uptake. This would appear to confirm the
      hypothesis that the differential and sequential induction of zonagenesis and
      vitellogenesis may reflect a general feature of teleost oogenesis.

PMID- 15718209
TI  - Lycopersicon esculentum lectin: an effective and versatile endothelial marker of
      normal and tumoral blood vessels in the central nervous system.
AB  - The binding of Lycopersicon esculentum lectin (LEA) to the vascular endothelium
      was studied in the central nervous system of rat, mouse and guinea pig at
      different developmental ages, and in a gliosarcoma model. Our observations showed
      that LEA consistently stained the entire vascular tree in the spinal cord and in
      the brain of all animal species at all developmental ages investigated. In the
      tumor model, the staining of the vascular network was very reproducible, enabled
      an easy identification of vascular profiles and displayed a higher efficiency
      when compared to two other commonly used vascular marker (EHS laminin and PECAM
      1). Moreover, our results showed that LEA staining was comparable in both
      vibratome and paraffin sections and could be easily combined with other markers
      in double labeling experiments. These observations indicate that LEA staining may
      represent an effective and versatile endothelial marker for the study of the
      vasculature of the central nervous system in different animal species and
      experimental conditions.

PMID- 15718210
TI  - The distribution and frequency of endocrine cells in the splenic lobe of grass
      lizard (Takydromus wolteri). An immunohistochemical study.
AB  - The regional distribution and frequency of the pancreatic endocrine cells in the
      splenic lobe of grass lizard, Takydromus wolteri, were studied by
      immunohistochemical (PAP) method using six types of specific mammalian antisera
      against bovine Sp-1/chromogranin (bCG), serotonin, insulin, glucagon,
      somatostatin and human pancreatic polypeptide (hPP). The pancreas was subdivided
      into two regions--islet kike and exocrine regions. The frequency of each
      immunoreactive (IR) endocrine cells was calculated as mean number/total 100 islet
      cells and as mean number/total 1,000 cells (including exocrine and endocrine
      cells) using automated image analysis process. In addition, the percentage of
      each IR cell was also calculated. All of six endocrine cells were demonstrated.
      They were dispersed in the whole pancreatic parenchyma between exocrine acinar
      cells, or they were also observed as islet like clusters. In islet-like regions,
      bCG-, insulin- and glucagon-IR cells were detected as one or two cell layer cords
      and they were located between this cell-cords with 14.30+/-5.62, 61.50+/-9.76 and
      26.50+/-9.31/100 cells frequencies, respectively. However, somatostatin-IR cells
      were mainly located in the peripheral parts not in cell-cords with 12.40+/
      4.86/100 cells, and no serotonin- and hPP-IR cells were demonstrated. In exocrine
      regions, all of bCG-, serotonin-, insulin-, glucagon-, somatostatin- and hPP-IR
      cells were detected and they occurred mainly among the exocrine parenchyma as
      solitary cells with 10.30+/-2.54, 0.80+/-0.63, 15.50+/-5.30, 5.80+/-2.66, 3.10+/
      1.29 and 11.00+/-3.33/1000 cells frequencies, respectively. In addition,
      serotonin-IR cells were mainly located between epithelia and connective tissue of
      pancreatic duct. Overall, there were 0.58+/-0.49% serotonin-, 56.44+/-9.35%
      insulin-, 23.73+/-8.22% glucagon-, 11.28+/-3.03% somatostatin- and 7.97+/-2.02%
      hPP-IR cells.

PMID- 15718211
TI  - Biomolecular identification of (CCTG)n mutation in myotonic dystrophy type 2
      (DM2) by FISH on muscle biopsy.
AB  - Myotonic dystrophy type 2 (DM2) is a dominantly inherited disorder with
      multisystemic clinical features, caused by a CCTG repeat expansion in intron 1 of
      the zinc finger protein 9 (ZNF9) gene. The mutant transcripts are retained in the
      nucleus forming multiple discrete foci also called ribonuclear inclusions. The
      size and the somatic instability of DM2 expansion complicate the molecular
      diagnosis of DM2. In our study fluorescence-labeled CAGG-repeat oligonucleotides
      were hybridized to muscle biopsies to investigate if fluorescence in situ
      hybridization (FISH), a relatively quick and simple procedure, could be used as a
      method to diagnose DM2. When FISH was performed with (CAGG)5 probe, nuclear foci
      of mutant RNA were present in all genetically confirmed DM2 patients (n=17) and
      absent in all patients with myotonic dystrophy type 1 (DM1; n=5) or with other
      muscular disease (n=17) used as controls. In contrast, foci were observed both in
      DM1 and DM2 myonuclei when muscle tissue were hybridized with (CAG)6CA probe
      indicating that this probe is not specific for DM2 identification. The consistent
      detection of ribonuclear inclusions in DM2 muscles and their absence in DM1, in
      agreement with the clinical diagnosis and with leukocyte (CCTG)n expansion,
      suggests that fluorescence in situ hybridization using (CAGG)5 probes, may be a
      specific method to distinguish between DM1 and DM2. Moreover, the procedure is
      simple, and readily applicable in any pathology laboratory.

PMID- 15718212
TI  - The Golgi apparatus is a primary site of intracellular damage after
      photosensitization with Rose Bengal acetate.
AB  - The aim of the present investigation was to elucidate whether the Golgi apparatus
      undergoes photodamage following administration of the fluorogenic substrates Rose
      Bengal acetate (RBAc) and irradiation at the appropriate wavelength. Human HeLa
      cells were treated in culture and the changes in the organization of the Golgi
      apparatus were studied using fluorescence confocal microscopy and electron
      microscopy, after immunocytochemical labeling. To see whether the cytoskeletal
      components primarily involved in vesicle traffic (i.e., microtubules) might also
      be affected, experiments of tubulin immunolabeling were performed. After
      treatment with RBAc and irradiation, cells were allowed to grow in drug-free
      medium for different times. 24 hr after irradiation, the cisternae of the Golgi
      apparatus became packed, and after 48-72 hr they appeared more fragmented and
      scattered throughout the cytoplasm; these changes in the organization of the
      Golgi cisternae were confirmed at electron microscopy. Interestingly enough,
      apoptosis was found to occur especially 48-72 h after irradiation, and apoptotic
      cells exhibited a dramatic fragmentation of the Golgi membranes. The
      immunolabeling with anti-tubulin antibody showed that microtubules were also
      affected by irradiation in RBAc-treated cells.

PMID- 15718213
TI  - Ultrastructural analysis of testes from mice fed on genetically modified soybean.
AB  - We have considered the possible effects of a diet containing genetically modified
      (GM) soybean on mouse testis. This organ, in fact, is a well known bioindicator
      and it has already been utilized, for instance, to monitor pollution by heavy
      metals. In this preliminary study, we have focussed our attention on Sertoli
      cells, spermatogonia and spermatocytes by means of immunoelectron microscopy. Our
      results point out that the immunolabelling for Sm antigen, hnRNPs, SC35 and RNA
      Polymerase II is decreased in 2 and 5 month-old GM-fed mice, and is restored to
      normal at 8 months. In GM-fed mice of all ages considered, the number of
      perichromatin granules is higher and the nuclear pore density lower. Moreover, we
      found enlargements in the smooth endoplasmic reticulum in GM-fed mice Sertoli
      cells. A possible role played by traces of the herbicide to which the soybean is
      resistant is discussed.

PMID- 15718216
TI  - Functional symptoms in neurology: management.

PMID- 15718217
TI  - Functional symptoms and signs in neurology: assessment and diagnosis.

PMID- 15718218
TI  - Cognitive assessment for clinicians.

PMID- 15718220
TI  - Recognising and evaluating disordered mental states: a guide for neurologists.

PMID- 15718219
TI  - Neurological syndromes which can be mistaken for psychiatric conditions.

PMID- 15718221
TI  - Depression and anxiety in epilepsy.

PMID- 15718222
TI  - Depression in neurological disorders: Parkinson's disease, multiple sclerosis,
      and stroke.

PMID- 15718223
TI  - Psychosis following head injury: a critical review.

PMID- 15718224
TI  - Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure
      by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus
      nivalis.
AB  - The plant lectins from Hippeastrum hybrid (HHA) and Galanthus nivalis (GNA) are
      50,000-D tetramers showing specificity for alpha-(1,3) and/or alpha-(1,6)-mannose
      oligomers. They inhibit HIV-1 infection at a 50% effective concentration of 0.2
      to 0.3 microg/ml. Escalating HHA or GNA concentrations (up to 500 microg/ml) led
      to the isolation of three HIV-1(III(B)) strains in CEM T cell cultures that were
      highly resistant to HHA and GNA, several other related mannose-specific plant
      lectins, and the monoclonal antibody 2G12, modestly resistant to the mannose
      specific cyanovirin, which is derived from a blue-green alga, but fully
      susceptible to other HIV entry inhibitors as well as HIV reverse transcriptase
      inhibitors. These mutant virus strains were devoid of up to seven or eight of 22
      glycosylation sites in the viral envelope glycoprotein gp120 because of mutations
      at the Asn or Thr/Ser sites of the N-glycosylation motifs. In one of the strains,
      a novel glycosylation site was created near a deleted glycosylation site. The
      affected glycosylation sites were predominantly clustered in regions of gp120
      that are not involved in the direct interaction with either CD4, CCR5, CXCR4, or
      gp41. The mutant viruses containing the deleted glycosylation sites were markedly
      more infectious in CEM T-cell cultures than wild-type virus.

PMID- 15718225
TI  - Modulation of voltage-gated potassium channels in human T lymphocytes by
      extracellular glutamate.
AB  - Glutamate is present in the plasma under tightly regulated concentrations.
      However, under conditions of immune deficiency, such as AIDS and malignancy, its
      plasma levels are highly elevated. In vitro, glutamate interacts with T
      lymphocytes, affecting mitogen-induced calcium responses, whereas at high doses,
      it impairs T lymphocyte proliferation, a process strongly dependent on the
      activity of voltage-gated potassium channels. In this study, we demonstrate novel
      dose-related effects of the endogenous ligand glutamate and its metabotropic and
      non-N-methyl-D-aspartic acid receptor agonists on the electrophysiological
      properties of native Kv1.3 channels of human T lymphocytes. Glutamate, at
      concentrations within normal plasma levels, positively modulates Kv1.3 channel
      gating, causing currents to activate faster and at significantly more
      hyperpolarized potentials, hence rendering the T lymphocyte readily responsive to
      immune stimuli. This effect is maximal at 1 microM Glu and is fully mimicked by a
      100 microM concentration of the metabotropic receptor agonist trans-(1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid. Most importantly, Glu, at concentrations
      > or =100 microM, which in vitro produce suppression of mitogen-induced
      proliferation, significantly decreases whole-cell potassium currents by
      increasing current and steady-state inactivation. This effect saturates at 1000
      microM and seems to result from the subsequent activation of low-affinity
      metabotropic Glu receptors, as suggested by specific agonist data. Therefore, the
      antiproliferative effects of high glutamate may, at least in part, result from
      its inhibitory effect on the potassium current, suggesting an in vivo
      immunosuppressive role of elevated plasma glutamate.

PMID- 15718226
TI  - Cytochrome b mutations that modify the ubiquinol-binding pocket of the cytochrome
      bc1 complex and confer anti-malarial drug resistance in Saccharomyces cerevisiae.
AB  - Atovaquone is a new anti-malarial agent that specifically targets the cytochrome
      bc1 complex and inhibits parasite respiration. A growing number of failures of
      this drug in the treatment of malaria have been genetically linked to point
      mutations in the mitochondrial cytochrome b gene. To better understand the
      molecular basis of atovaquone resistance in malaria, we introduced five of these
      mutations, including the most prevalent variant found in Plasmodium falciparum
      (Y268S), into the cytochrome b gene of the budding yeast Saccharomyces cerevisiae
      and thus obtained cytochrome bc1 complexes resistant to inhibition by atovaquone.
      By modeling the variations in cytochrome b structure and atovaquone binding with
      the mutated bc1 complexes, we obtained the first quantitative explanation for the
      molecular basis of atovaquone resistance in malaria parasites.

PMID- 15718227
TI  - Mutational analysis of the stator subunit E of the yeast V-ATPase.
AB  - Subunit E is a component of the peripheral stalk(s) that couples membrane and
      peripheral subunits of the V-ATPase complex. In order to elucidate the function
      of subunit E, site-directed mutations were performed at the amino terminus and
      carboxyl terminus. Except for S78A and D233A/T202A, which exhibited V(1)V(o)
      assembly defects, the function of subunit E was resistant to mutations. Most
      mutations complemented the growth phenotype of vma4Delta mutants, including T6A
      and D233A, which only had 25% of the wild-type ATPase activity. Residues Ser-78
      and Thr-202 were essential for V(1)V(o) assembly and function. The mutation S78A
      destabilized subunit E and prevented assembly of V(1) subunits at the membranes.
      Mutant T202A membranes exhibited 2-fold increased V(max) and about 2-fold less of
      V(1)V(o) assembly; the mutation increased the specific activity of V(1)V(o) by
      enhancing the k(cat) of the enzyme 4-fold. Reduced levels of V(1)V(o) and V(o)
      complexes at T202A membranes suggest that the balance between V(1)V(o) and V(o)
      was not perturbed; instead, cells adjusted the amount of assembled V-ATPase
      complexes in order to compensate for the enhanced activity. These results
      indicated communication between subunit E and the catalytic sites at the A(3)B(3)
      hexamer and suggest potential regulatory roles for the carboxyl end of subunit E.
      At the carboxyl end, alanine substitution of Asp-233 significantly reduced ATP
      hydrolysis, although the truncation 229-233Delta and the point mutation K230A did
      not affect assembly and activity. The implication of these results for the
      topology and functions of subunit E within the V-ATPase complex are discussed.

PMID- 15718228
TI  - Disabled1 regulates the intracellular trafficking of reelin receptors.
AB  - Reelin is a huge secreted protein that controls proper laminar formation in the
      developing brain. It is generally believed that tyrosine phosphorylation of
      Disabled1 (Dab1) by Src family tyrosine kinases is the most critical downstream
      event in Reelin signaling. The receptors for Reelin belong to the low density
      lipoprotein receptor family, most of whose members undergo regulated
      intracellular trafficking. In this study, we propose novel roles for Dab1 in
      Reelin signaling. We first demonstrated that cell surface expression of Reelin
      receptors was decreased in Dab1-deficient neurons. In heterologous cells, Dab1
      enhanced cell surface expression of Reelin receptors, and this effect was
      mediated by direct interaction with the receptors. Moreover, Dab1 did not stably
      associate with the receptors at the plasma membrane in the resting state. When
      Reelin was added to primary cortical neurons, Dab1 was recruited to the
      receptors, and its tyrosine residues were phosphorylated. Although Reelin and
      Dab1 colocalized well shortly after the addition of Reelin, Dab1 was no longer
      associated with internalized Reelin. When Src family tyrosine kinases were
      inhibited, internalization of Reelin was severely abrogated, and Reelin
      colocalized with Dab1 near the plasma membrane for a prolonged period. Taken
      together, these results indicate that Dab1 regulates both cell surface expression
      and internalization of Reelin receptors, and these regulations may play a role in
      correct laminar formation in the developing brain.

PMID- 15718229
TI  - Structural and functional analysis of the C-terminal STAS (sulfate transporter
      and anti-sigma antagonist) domain of the Arabidopsis thaliana sulfate transporter
      SULTR1.2.
AB  - The C-terminal region of sulfate transporters from plants and animals belonging
      to the SLC26 family members shares a weak but significant similarity with the
      Bacillus sp. anti-anti-sigma protein SpoIIAA, thus defining the STAS domain
      (sulfate transporter and anti-sigma antagonist). The present study is a
      structure/function analysis of the STAS domain of SULTR1.2, an Arabidopsis
      thaliana sulfate transporter. A three-dimensional model of the SULTR1.2 STAS
      domain was built which indicated that it shares the SpoIIAA folds. Moreover, the
      phosphorylation site, which is necessary for SpoIIAA activity, is conserved in
      the SULTR1.2 STAS domain. The model was used to direct mutagenesis studies using
      a yeast mutant defective for sulfate transport. Truncation of the whole SULTR1.2
      STAS domain resulted in the loss of sulfate transport function. Analyses of small
      deletions and mutations showed that the C-terminal tail of the SULTR1.2 STAS
      domain and particularly two cysteine residues plays an important role in sulfate
      transport by SULTR1.2. All the substitutions made at the putative phosphorylation
      site Thr-587 led to a complete loss of the sulfate transport function of
      SULTR1.2. The reduction or suppression of sulfate transport of the SULTR1.2
      mutants in yeast was not due to an incorrect targeting to the plasma membrane.
      Both our three-dimensional modeling and mutational analyses strengthen the
      hypothesis that the SULTR1.2 STAS domain is involved in protein-protein
      interactions that could control sulfate transport.

PMID- 15718230
TI  - Metal ion-dependent effects of clioquinol on the fibril growth of an amyloid
      {beta} peptide.
AB  - Although metal ions such as Cu(2+), Zn(2+), and Fe(3+) are implicated to play a
      key role in Alzheimer disease, their role is rather complex, and comprehensive
      understanding is not yet obtained. We show that Cu(2+) and Zn(2+) but not Fe(3+)
      renders the amyloid beta peptide, Abeta(1-40), nonfibrillogenic in nature.
      However, preformed fibrils of Abeta(1-40) were stable when treated with these
      metal ions. Consequently, fibril growth of Abeta(1-40) could be switched on/off
      by switching the molecule between its apo- and holo-forms. Clioquinol, a
      potential drug for Alzheimer disease, induced resumption of the Cu(2+)-suppressed
      but not the Zn(2+)-suppressed fibril growth of Abeta(1-40). The observed
      synergistic effect of clioquinol and Zn(2+) suggests that Zn(2+)-clioquinol
      complex effectively retards fibril growth. Thus, clioquinol has dual effects;
      although it disaggregates the metal ion-induced aggregates of Abeta(1-40) through
      metal chelation, it further retards the fibril growth along with Zn(2+). These
      results indicate the mechanism of metal ions in suppressing Abeta amyloid
      formation, as well as providing information toward the use of metal ion
      chelators, particularly clioquinol, as potential drugs for Alzheimer disease.

PMID- 15718231
TI  - Anchor structure of staphylococcal surface proteins. V. Anchor structure of the
      sortase B substrate IsdC.
AB  - Staphylococcus aureus sortase A cleaves surface protein precursors bearing C
      terminal LPXTG motif sorting signals between the threonine and glycine residues.
      Using lipid II precursor as cosubstrate, sortase A catalyzes the amide linkage
      between the carboxyl group of threonine and the amino group of pentaglycine cross
      bridges, thereby tethering C-terminal ends of surface proteins to the bacterial
      cell wall envelope. Staphylococcal sortase B also anchors its only known
      substrate, the IsdC precursor with a C-terminal NPQTN motif sorting signal, to
      the cell wall envelope. Herein, we determined the cell wall anchor structure of
      IsdC. The sorting signal of IsdC is cleaved between threonine and asparagine of
      the NPQTN motif, and the carboxyl group of threonine is amide-linked to the amino
      group of pentaglycine crossbridges. In contrast to sortase A substrates, the
      anchor structure of IsdC displays shorter glycan strands and significantly less
      cell wall cross-linking. A model is proposed whereby sortases A and B recognize
      unique features of sorting signals and peptidoglycan substrates to deposit
      proteins with distinct topologies in the cell wall envelope.

PMID- 15718232
TI  - Novel characteristics of the biological properties of the yeast Saccharomyces
      cerevisiae eukaryotic initiation factor 2A.
AB  - Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the
      initiator methionyl-tRNA (Met-tRNA(i)) to 40 S ribosomal subunits in a codon
      dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon
      to bind initiator tRNA to 40 S subunits. We show here that yeast eIF2A
      genetically interacts with initiation factor eIF4E, suggesting that both proteins
      function in the same pathway. The double eIF2A/eIF4E-ts mutant strain displays a
      severe slow growth phenotype, which correlated with the accumulation of 85% of
      the double mutant cells arrested at the G(2)/M border. These cells also exhibited
      a disorganized actin cytoskeleton and elevated actin levels, suggesting that
      eIF2A might be involved in controlling the expression of genes involved in
      morphogenic processes. Further insights into eIF2A function were gained from the
      studies of eIF2A distribution in ribosomal fractions obtained from either an
      eIF5BDelta (fun12Delta) strain or a eIF3b-ts (prt1-1) strain. It was found that
      the binding of eIF2A to 40 and 80 S ribosomes was not impaired in either strain.
      We also found that eIF2A functions as a suppressor of Ure2p internal ribosome
      entry site-mediated translation in yeast cells. The regulation of expression from
      the URE2 internal ribosome entry site appears to be through the levels of eIF2A
      protein, which has been found to be inherently unstable with a half-life of
      approximately 17 min. It was hypothesized that this instability allows for
      translational control through the level of eIF2A protein in yeast cells.

PMID- 15718233
TI  - The crucial role of conserved intermolecular H-bonds inaccessible to the solvent
      in formation and stabilization of the TL5.5 SrRNA complex.
AB  - Analysis of the structures of two complexes of 5 S rRNA with homologous ribosomal
      proteins, Escherichia coli L25 and Thermus thermophilus TL5, revealed that amino
      acid residues interacting with RNA can be divided into two different groups. The
      first group consists of non-conserved residues, which form intermolecular
      hydrogen bonds accessible to solvent. The second group, comprised of strongly
      conserved residues, form intermolecular hydrogen bonds that are shielded from
      solvent. Site-directed mutagenesis was used to introduce mutations into the RNA
      binding site of protein TL5. We found that replacement of residues of the first
      group does not influence the stability of the TL5.5 S rRNA complex, whereas
      replacement of residues of the second group leads to destabilization or
      disruption of the complex. Stereochemical analysis shows that the replacements of
      residues of the second group always create complexes with uncompensated losses of
      intermolecular hydrogen bonds. We suggest that these shielded intermolecular
      hydrogen bonds are responsible for the recognition between the protein and RNA.

PMID- 15718234
TI  - Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63
      linked multiubiquitin chains.
AB  - Mutations in alpha-synuclein, Parkin, and UCH-L1 cause heritable forms of
      Parkinson disease. Unlike alpha-synuclein, for which no precise biochemical
      function has been elucidated, Parkin functions as a ubiquitin E3 ligase, and UCH
      L1 is a deubiquitinating enzyme. The E3 ligase activity of Parkin in Parkinson
      disease is poorly understood and is further obscured by the fact that
      multiubiquitin chains can be formed through distinct types of linkages that
      regulate diverse cellular processes. For instance, ubiquitin lysine 48-linked
      multiubiquitin chains target substrates to the proteasome, whereas ubiquitin
      lysine 63-linked chains control ribosome function, protein sorting and
      trafficking, and endocytosis of membrane proteins. It is notable in this regard
      that ubiquitin lysine 63-linked chains promote the degradation of membrane
      proteins by the lysosome. Because both Parkin and alpha-synuclein can regulate
      the activity of the dopamine transporter, we investigated whether they influenced
      ubiquitin lysine 63-linked chain assembly. These studies revealed novel
      biochemical activities for both Parkin and alpha-synuclein. We determined that
      Parkin functions with UbcH13/Uev1a, a dimeric ubiquitin-conjugating enzyme, to
      assemble ubiquitin lysine 63-linked chains. Our results and the results of others
      indicate that Parkin can promote both lysine 48- and lysine 63-linked ubiquitin
      chains. alpha-Synuclein also stimulated the assembly of lysine 63-linked
      ubiquitin chains. Because UCH-L1, a ubiquitin hydrolase, was recently reported to
      form lysine 63-linked conjugates, it is evident that three proteins that are
      genetically linked to Parkinson disease can contribute to lysine 63
      multiubiquitin chain formation.

PMID- 15718235
TI  - Beyond the Xi: macroH2A chromatin distribution and post-translational
      modification in an avian system.
AB  - MacroH2A (mH2A) is a histone variant that is enriched in the inactivated X
      chromosomes of mammalian females. To characterize the role of this protein in
      other nuclear processes we isolated chromatin particles from chicken liver, a
      vertebrate system that does not undergo X-inactivation. Chromatin digestion and
      fractionation studies determined that mH2A is evenly distributed at several
      levels of chromatin structure and stabilizes the nucleosome core particle in
      solution. However, at the level of the chromatosome, selective salt precipitation
      showed the existence of a mutually exclusive relationship between mH2A and H1,
      which may reveal functional redundancy between these proteins. Two-dimensional
      gel electrophoresis demonstrated the presence of one major population of mH2A
      containing nucleosomes, which may become ADP-ribosylated. This report provides
      new clues into how mH2A distribution and a previously unidentified post
      translational modification may help regulate the repression of autosomal
      chromatin.

PMID- 15718236
TI  - My contributions to science and society.

PMID- 15718237
TI  - Masters of DNA.

PMID- 15718238
TI  - Functional characterization of the MENTAL domain.
AB  - Human metastatic lymph node (MLN) 64 is composed of two conserved regions. The
      amino terminus contains a conserved membrane-spanning MENTAL (MLN64 NH(2)
      terminal) domain shared with an unique protein called MENTHO (MLN64 NH(2)
      terminal domain homologue) and targets the protein to late endosome. The carboxyl
      terminal domain is composed of a cholesterol binding steroidogenic acute
      regulatory-related lipid transfer domain exposed to the cytoplasm. MENTHO
      overexpression leads to the accumulation of enlarged endosomes. In this study, we
      show that MLN64 overexpression also induces the formation of enlarged endosomes,
      an effect that is probably mediated by the MENTAL domain. Using an in vivo
      photocholesterol binding assay, we find that the MENTAL domain of MLN64 is a
      cholesterol binding domain. Moreover, glutathione S-transferase pull-down or co
      immunoprecipitation experiments demonstrate that this domain mediates homo- and
      hetero-interaction of MLN64 and MENTHO. In living cells, the expression of paired
      yellow fluorescent and cyan fluorescent fusion proteins show MENTHO homo
      interaction and its interaction with MLN64. These data indicate that within late
      endosomal membranes, MLN64 and MENTHO define discrete cholesterol-containing
      subdomains. The MENTAL domain might serve to maintain cholesterol at the membrane
      of late endosomes prior to its shuttle to cytoplasmic acceptor(s).

PMID- 15718239
TI  - A mitochondrial NADH-dependent fumarate reductase involved in the production of
      succinate excreted by procyclic Trypanosoma brucei.
AB  - Trypanosoma brucei is a parasitic protist responsible for sleeping sickness in
      humans. The procyclic stage of T. brucei expresses a soluble NADH-dependent
      fumarate reductase (FRDg) in the peroxisome-like organelles called glycosomes.
      This enzyme is responsible for the production of about 70% of the excreted
      succinate, the major end product of glucose metabolism in this form of the
      parasite. Here we functionally characterize a new gene encoding FRD (FRDm1)
      expressed in the procyclic stage. FRDm1 is a mitochondrial protein, as evidenced
      by immunolocalization, fractionation of digitonin-permeabilized cells, and
      expression of EGFP-tagged FRDm1 in the parasite. RNA interference was used to
      deplete FRDm1, FRDg, or both together. The analysis of the resulting mutant cell
      lines showed that FRDm1 is responsible for 30% of the cellular NADH-FRD activity,
      which solves a long standing debate regarding the existence of a mitochondrial
      FRD in trypanosomatids. FRDg and FRDm1 together account for the total NADH-FRD
      activity in procyclics, because no activity was measured in the double mutant
      lacking expression of both proteins. Analysis of the end products of 13C-enriched
      glucose excreted by these mutant cell lines showed that FRDm1 contributes to the
      production of between 14 and 44% of the succinate excreted by the wild type
      cells. In addition, depletion of one or both FRD enzymes results in up to 2-fold
      reduction of the rate of glucose consumption. We propose that FRDm1 is involved
      in the maintenance of the redox balance in the mitochondrion, as proposed for the
      ancestral soluble FRD presumably present in primitive anaerobic cells.

PMID- 15718240
TI  - Towards a structure for a TSG-6.hyaluronan complex by modeling and NMR
      spectroscopy: insights into other members of the link module superfamily.
AB  - The Link module from human TSG-6, a hyaladherin with roles in ovulation and
      inflammation, has a hyaluronan (HA)-binding groove containing two adjacent
      tyrosine residues that are likely to form CH-pi stacking interactions with
      sequential rings in the sugar. We have used this observation to construct a model
      of a protein.HA complex, which was then tested against existing experimental
      information and by acquisition of new NMR data sets of [(13)C, (15)N]HA (8-mer)
      complexed with unlabeled protein. A major finding of this analysis was that
      acetamido side chains of two GlcNAc rings fit into hydrophobic pockets on either
      side of the adjacent tyrosines, providing a selectivity mechanism of HA over
      other polysaccharides. Furthermore, two basic residues have a separation that
      matches that of glucuronic acids in the sugar, consistent with the formation of
      salt bridges; NMR experiments at a range of pH values identified protein groups
      that titrate due to their proximity to a free carboxylate in HA. Sequence
      alignment and construction of homology models for all human Link modules in their
      HA-bound states revealed that many of these features are conserved across the
      superfamily, thus allowing the prediction of functionally important residues. In
      the case of cartilage link protein, its two Link modules were docked together
      (using bound HA as a guide), identifying hydrophobic residues likely to form an
      intra-Link module interface as well as amino acids that could be involved in
      supporting intermolecular interactions between link proteins and chondroitin
      sulfate proteoglycans. Here, we propose a mechanism for ternary complex formation
      that generates higher order helical structures, as may exist in cartilage
      aggregates.

PMID- 15718241
TI  - Statins cause intracellular accumulation of amyloid precursor protein, beta
      secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent
      mechanism.
AB  - The use of statins, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that
      block the synthesis of mevalonate (and downstream products such as cholesterol
      and nonsterol isoprenoids), as a therapy for Alzheimer disease is currently the
      subject of intense debate. It has been reported that statins reduce the risk of
      developing the disorder, and a link between cholesterol and Alzheimer disease
      pathophysiology has been proposed. Moreover, experimental studies focusing on the
      cholesterol-dependent effects of statins have demonstrated a close association
      between cellular cholesterol levels and amyloid production. However, evidence
      suggests that statins are pleiotropic, and the potential cholesterol-independent
      effects of statins on amyloid precursor protein (APP) metabolism and amyloid beta
      peptide (A beta) genesis are unknown. In this study, we developed a novel in
      vitro system that enabled the discrete analysis of cholesterol-dependent and 
      independent (i.e. isoprenoid-dependent) statin effects on APP cleavage and A beta
      formation. Given the recent interest in the role that intracellular A beta may
      play in Alzheimer disease, we analyzed statin effects on both secreted and cell
      associated A beta. As reported previously, low cellular cholesterol levels
      favored the alpha-secretase pathway and decreased A beta secretion presumably
      within the endocytic pathway. In contrast, low isoprenoid levels resulted in the
      accumulation of APP, amyloidogenic fragments, and A beta likely within
      biosynthetic compartments. Importantly, low cholesterol and low isoprenoid levels
      appeared to have completely independent effects on APP metabolism and A beta
      formation. Although the implications of these effects for Alzheimer disease
      pathophysiology have yet to be investigated, to our knowledge, these results
      provide the first evidence that isoprenylation is involved in determining levels
      of intracellular A beta.

PMID- 15718242
TI  - Structural basis for the specificity of the reducing end xylose-releasing exo
      oligoxylanase from Bacillus halodurans C-125.
AB  - Reducing end xylose-releasing exo-oligoxylanase from Bacillus halodurans C-125
      (Rex) hydrolyzes xylooligosaccharides whose degree of polymerization is greater
      than or equal to 3, releasing the xylose unit at the reducing end. It is a unique
      exo-type glycoside hydrolase that recognizes the xylose unit at the reducing end
      in a very strict manner, even discriminating the beta-anomeric hydroxyl
      configuration from the alpha-anomer or 1-deoxyxylose. We have determined the
      crystal structures of Rex in unliganded and complex forms at 1.35-2.20-A
      resolution and revealed the structural aspects of its three subsites ranging from
      -2 to +1. The structure of Rex was compared with those of endo-type enzymes in
      glycoside hydrolase subfamily 8a (GH-8a). The catalytic machinery of Rex is
      basically conserved with other GH-8a enzymes. However, subsite +2 is blocked by a
      barrier formed by a kink in the loop before helix alpha10. His-319 in this loop
      forms a direct hydrogen bond with the beta-hydroxyl of xylose at subsite +1,
      contributing to the specific recognition of anomers at the reducing end.

PMID- 15718243
TI  - pH-dependent intraluminal organization of mucin granules in live human
      mucous/goblet cells.
AB  - To study the mechanism of gel-forming mucin packaging within mucin granules, we
      generated human mucous/goblet cells stably expressing a recombinant MUC5AC domain
      fused to green fluorescent protein (GFP). The fusion protein, named SHGFP
      MUC5AC/CK, accumulated in the granules together with native MUC5AC. Inhibition of
      protein synthesis or disorganization of the Golgi complex did not result in
      diminished intragranular SHGFP-MUC5AC/CK signals, consistent with long-term
      storage of the fusion protein. However, SHGFP-MUC5AC/CK was rapidly discharged
      from the granules upon incubation of the cells with ATP, an established mucin
      secretagogue. Several criteria indicated that SHGFP-MUC5AC/CK was not covalently
      linked to endogenous MUC5AC. Analysis of fluorescence recovery after
      photobleaching suggested that the intragranular SHGFP-MUC5AC/CK mobile fraction
      and mobility were significantly lower than in the endoplasmic reticulum lumen.
      Incubation of the cells with bafilomycin A1, a specific inhibitor of the vacuolar
      H+-ATPase, did not alter the fusion protein mobility, although it significantly
      increased (approximately 20%) the intragranular SHGFP-MUC5AC/CK mobile fraction.
      In addition, the granules in bafilomycin-incubated cells typically exhibited a
      heterogeneous intraluminal distribution of the fluorescent fusion protein. These
      results are consistent with a model of mucin granule intraluminal organization
      with two phases: a mobile phase in which secretory proteins diffuse as in the
      endoplasmic reticulum lumen but at a lower rate and an immobile phase or matrix
      in which proteins are immobilized by noncovalent pH-dependent interactions. An
      intraluminal acidic pH, maintained by the vacuolar H+-ATPase, is one of the
      critical factors for secretory protein binding to the immobile phase and also for
      its organization.

PMID- 15718244
TI  - Identification of conserved amino acids N-terminal of the PKC epsilon C1b domain
      crucial for protein kinase C epsilon-mediated induction of neurite outgrowth.
AB  - We have shown previously that protein kinase C (PKC) epsilon can induce neurite
      outgrowth independently of its catalytic activity via a region encompassing its
      C1 domains. In this study we aimed at identifying specific amino acids in this
      region crucial for induction of neurite outgrowth. Deletion studies demonstrated
      that only 4 amino acids N-terminal and 20 residues C-terminal of the C1 domains
      are necessary for neurite induction. The corresponding regions from all other
      novel isoforms but not from PKCalpha were also neuritogenic. Further mutation
      studies indicated that amino acids immediately N-terminal of the C1a domain are
      important for plasma membrane localization and thereby for neurite induction.
      Addition of phorbol ester made this construct neurite-inducing. However, mutation
      of amino acids flanking the C1b domain reduced the neurite-inducing capacity even
      in the presence of phorbol esters. Sequence alignment highlighted an 8-amino acid
      long sequence N-terminal of the C1b domain that is conserved in all novel PKC
      isoforms. Specifically, we found that mutations of either Phe-237, Val-239, or
      Met-241 in PKCepsilon completely abolished the neurite-inducing capacity of
      PKCepsilon C1 domains. Phorbol ester treatment could not restore neurite
      induction but led to a plasma membrane translocation. Furthermore, if 12 amino
      acids were included N-terminal of the C1b domain, the C1a domain was dispensable
      for neurite induction. In conclusion, we have identified a highly conserved
      sequence N-terminal of the C1b domain that is crucial for neurite induction by
      PKCepsilon, indicating that this motif may be critical for some morphological
      effects of PKC.

PMID- 15718246
TI  - Molecular and functional characterization of the electroneutral Na/HCO3
      cotransporter NBCn1 in rat hippocampal neurons.
AB  - We examined molecular and electrophysiological properties of the electroneutral
      sodium/bicarbonate cotransporter (NBCn1) that is present in rat hippocampal
      neurons. By PCR, a deletion variant (NBCn1-E) that lacks 123 amino acids in the
      cytoplasmic N-terminal domain was found in adult neurons. The previously
      characterized NBCn1-B, which does not have the deletion, was detected in
      embryonic neurons. In Xenopus oocytes, NBCn1-E raised the intracellular pH in the
      presence of HCO(3) without significantly affecting the membrane potential.
      Despite this electroneutral cotransport activity, the transporter mediated a
      steady-state current that positively shifted the resting potential by almost 30
      mV. The mean reversal potential of the steady-state current was -21.2 mV, close
      to the resting potential of -21.4 mV. The reversal potential shifted 26 mV in
      response to a 10-fold increase of external Na(+) for concentrations above 10 mm.
      The current activity mediated by the transporter was unaffected by K(+), Mg(2+),
      Ca(2+), or Cl(-). Stable expression of NBCn1-E in human embryonic kidney cells
      also evoked an inward current that shifted the resting potentials more positive
      compared with the sham-transfected controls. In primary cultures of embryonic
      hippocampal neurons, the NBCn1 protein was localized in somatodendrites and
      synapses. NBCn1 protein was partially colocalized with the postsynaptic density
      protein PSD-95. Single-cell PCR showed that NBCn1 mRNA expression was present in
      both gamma-aminobutyric acid (GABA)ergic and non-GABAergic neurons. We propose
      that NBCn1 in hippocampal neurons may affect neuronal activity by regulating
      local pH as well as steady-state inward currents at synapses.

PMID- 15718245
TI  - Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking
      and long term synaptic depression.
AB  - Expression of N-methyl d-aspartate (NMDA) receptor-dependent homosynaptic long
      term depression at synapses in the hippocampus and neocortex requires the
      persistent dephosphorylation of postsynaptic protein kinase A substrates. An
      attractive mechanism for expression of long term depression is the loss of
      surface AMPA (alpha-amino-3-hydroxy-5-methylisoxazale-4-propionate) receptors at
      synapses. Here we show that a threshold level of NMDA receptor activation must be
      exceeded to trigger a stable loss of AMPA receptors from the surface of cultured
      hippocampal neurons. NMDA also causes displacement of protein kinase A from the
      synapse, and inhibiting protein kinase A (PKA) activity mimics the NMDA-induced
      loss of surface AMPA receptors. PKA is targeted to the synapse by an interaction
      with the A kinase-anchoring protein, AKAP79/150. Disruption of the PKA-AKAP
      interaction is sufficient to cause a long-lasting reduction in synaptic AMPA
      receptors in cultured neurons. In addition, we demonstrate in hippocampal slices
      that displacement of PKA from AKADs occludes synaptically induced long term
      depression. These data indicate that synaptic anchoring of PKA through
      association with AKAPs plays an important role in the regulation of AMPA receptor
      surface expression and synaptic plasticity.

PMID- 15718247
TI  - Functional consequences of polyamine synthesis inhibition by L-alpha
      difluoromethylornithine (DFMO): cellular mechanisms for DFMO-mediated
      ototoxicity.
AB  - L-Alpha-difluoromethylornithine (DFMO) is a chemopreventive agent for colon
      cancer in clinical trials. Yet, the drug produces an across-frequency elevation
      of the hearing threshold, suggesting that DFMO may affect a common trait along
      the cochlear spiral. The mechanism for the ototoxic effects of DFMO remains
      uncertain. The cochlear duct is exclusively endowed with endocochlear potential
      (EP). EP is a requisite for normal sound transduction, as it provides the
      electromotive force that determines the magnitude of the receptor potential of
      hair cells. EP is generated by the high throughput of K(+) across cells of the
      stria vascularis, conferred partly by the activity of Kir4.1 channels. Here, we
      show that the ototoxicity of DFMO may be mediated by alteration of the inward
      rectification of Kir4.1 channels, resulting in a marked reduction in EP. These
      findings are surprising given that the present model for EP generation asserts
      that Kir4.1 confers the outflow of K(+) in the stria vascularis. We have proposed
      an alternative model. These findings should also enable the rational design of
      new pharmaceuticals devoid of the untoward effect of DFMO.

PMID- 15718248
TI  - Cancer incidence and mortality in Europe, 2004.
AB  - BACKGROUND: There are no recent estimates of the incidence and mortality from
      cancer at a European level. Those data that are available generally refer to the
      mid-1990s and are of limited use for cancer control planning. We present
      estimates of the cancer burden in Europe in 2004, including data for the (25
      Member States) European Union. METHODS: The most recent sources of incidence and
      mortality data available in the Descriptive Epidemiology Group at IARC were
      applied to population projections to derive the best estimates of the burden of
      cancer, in terms of incidence and mortality, for Europe in 2004. RESULTS: In 2004
      in Europe, there were an estimated 2,886,800 incident cases of cancer diagnosed
      and 1,711,000 cancer deaths. The most common incident form of cancer was lung
      cancer (13.3% of all incident cases), followed by colorectal cancer (13.2%) and
      breast cancer (13%). Lung cancer was also the most common cause of cancer death
      (341,800 deaths), followed by colorectal (203,700), stomach (137,900) and breast
      (129,900). CONCLUSIONS: With an estimated 2.9 million new cases (54% occurring in
      men, 46% in women) and 1.7 million deaths (56% in men, 44% in women) each year,
      cancer remains an important public health problem in Europe, and the ageing of
      the European population will cause these numbers to continue to increase even if
      age-specific rates remain constant. To make great progress quickly against cancer
      in Europe, the need is evident to make a concerted attack on the big killers:
      lung, colorectal, breast and stomach cancer. Stomach cancer rates are falling
      everywhere in Europe and public health measures are available to reduce the
      incidence and mortality of lung cancer, colorectal cancer and breast cancer.

PMID- 15718249
TI  - NOD1 variation, immunoglobulin E and asthma.
AB  - Asthma is a familial inflammatory disease of the airways of the lung. Microbial
      exposures in childhood protect against asthma through unknown mechanisms. The
      innate immune system is able to identify microbial components through a variety
      of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that
      initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The
      NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to
      asthma. We carried out a systematic search for polymorphism in the gene. We found
      an insertion-deletion polymorphism (ND(1)+32656) near the beginning of intron IX
      that accounted for approximately 7% of the variation in IgE in two panels of
      families (P<0.0005 in each). Allele*2 (the insertion) was associated with high
      IgE levels. The same allele was strongly associated with asthma in an independent
      study of 600 asthmatic children and 1194 super-normal controls [odds ratio (OR)
      6.3; 95% confidence interval (CI) 1.4-28.3, dominant model]. Differential binding
      of the two ND(1)+32656 alleles was observed to a protein from nuclei of the Calu
      3 epithelial cell line. In an accompanying study, the deletion allele
      (ND(1)+32656*1) was found to be associated with inflammatory bowel disease. The
      results indicate that intracellular recognition of specific bacterial products
      affects the presence of childhood asthma.

PMID- 15718250
TI  - Relapsing diabetes can result from moderately activating mutations in KCNJ11.
AB  - Neonatal diabetes can either remit and hence be transient or else may be
      permanent. These two phenotypes were considered to be genetically distinct.
      Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes
      (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of
      the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of
      permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11
      mutations also result in marked developmental delay and epilepsy. These mutations
      are more severe on functional characterization. We investigated whether mutations
      in KCNJ11 could also give rise to TNDM. We identified the three novel
      heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with
      clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The
      mutations co-segregated with diabetes within families and were not found in 100
      controls. All probands had insulin-treated diabetes diagnosed in the first 4
      months and went into remission by 7-14 months. Functional characterization of the
      TNDM associated mutations was performed by expressing the mutated Kir6.2 with
      SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a
      reduction in the sensitivity to ATP when compared with wild-type (IC(50)
      approximately 30 versus approximately 7 microM, P-value for is all <0.01);
      however, this was less profoundly reduced than with the PNDM associated
      mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for
      remitting as well as permanent diabetes. This suggests that a fixed ion channel
      abnormality can result in a fluctuating glycaemic phenotype. The multiple
      phenotypes associated with activating KCNJ11 mutations may reflect their severity
      in vitro.

PMID- 15718251
TI  - Differential requirement of signal pathways for benzo[a]pyrene (B[a]P)-induced
      nitric oxide synthase (iNOS) in rat esophageal epithelial cells.
AB  - Overexpression of inducible nitric oxide synthase (iNOS) has been reported in
      several human cancers, including esophageal squamous cell carcinoma (SCC).
      Benzo[a]pyrene (B[a]P), a polycyclic hydrocarbon carcinogen found in tobacco
      smoke and in the environment, induces cancer in multiple organ sites in animals
      and may be a causative agent for certain human cancers, such as esophageal
      cancer. In the present study, the effects of B[a]P on the induction of iNOS and
      the signaling pathways that lead to the induction were investigated in cultured
      rat esophageal epithelial (RE-149) cells. Treatment of RE-149 cells with B[a]P
      led to a marked increase in the expression of iNOS. The induction of iNOS by
      B[a]P was found to occur through an extracellular signal-regulated protein
      kinases (ERKs)-dependent pathway, since inhibition of ERKs by either pretreatment
      of RE-149 cells with PD98059, an inhibitor of ERKs upstream kinase MEK1/2, or
      overexpression of DN-ERK2, blocked the induction of iNOS by B[a]P. Furthermore,
      impairing nuclear factor-kappaB (NFkappaB) activation by either NEMO-BDBP, an
      NFkappaB specific inhibitor, or overexpression of DN-IkappaBalpha or IKK-KM
      markedly inhibited the expression of B[a]P-induced iNOS, suggesting that the
      NFkappaB pathway is also required for the induction of iNOS by B[a]P. In
      addition, treatment of RE-149 cells with either SB202190, a p38 kinase inhibitor,
      or c-JunN-terminal kinase inhibitor II, resulted in an increased induction of
      iNOS. Pretreatment of RE-149 cells with wortmannin, a PI-3K inhibitor, or with
      rapamycin, an mTOR/p70S6K pathway inhibitor, had no effect on the expression of
      iNOS. These results suggest that B[a]P initiates the signaling pathways leading
      to the induction of iNOS in cultured rat esophageal epithelial cells. In view of
      the potential role of iNOS in the development of esophageal SCC in humans, we
      speculate that the induction of iNOS by B[a]P may be one mechanism by which B[a]P
      could produce carcinogenic effects in the human esophagus.

PMID- 15718252
TI  - Reduced E-cadherin expression contributes to the loss of p27kip1-mediated
      mechanism of contact inhibition in thyroid anaplastic carcinomas.
AB  - In the present study, we have characterized several human thyroid cancer cell
      lines of different histotypes for their responsiveness to contact inhibition. We
      found that cells derived from differentiated carcinoma (TPC-1, WRO) arrest in
      G(1) phase at confluence, whereas cells derived from anaplastic carcinoma (ARO,
      FRO and FB1) continue to grow after reaching confluence. Furthermore, we provide
      experimental evidence that the axis, E-cadherin/beta-catenin/p27(Kip1),
      represents an integral part of the regulatory mechanism that controls
      proliferation at a high cell density, whose disruption may play a key role in
      determining the clinical behaviour of thyroid cancer. This conclusion derives
      from the finding that: (i) the expression of p27(Kip1) is enhanced at high cell
      density only in cells responsive to contact inhibition (TPC-1, WRO), but not in
      contact-inhibition resistant cells (ARO, FRO or FB1 cells); (ii) the increase in
      p27(Kip1) also resulted in increased levels of p27(Kip1) bound to cyclin E-Cdk2
      complex, a reduction in cyclin E-Cdk2 activity and dephosphorylation of the
      retinoblastoma protein; (iii) antisense inhibition of p27(Kip1) upregulation at
      high cell density in confluent-sensitive cells completely prevents the confluence
      induced growth arrest; (iv) proper expression and/or membrane localization of E
      cadherin is observed only in cells responsive to contact inhibition (TPC-1, NPA,
      WRO) but not in unresponsive cells (ARO, FRO or FB1); (v) disruption of E
      cadherin-mediated cell-cell contacts at high cell density induced by an anti-E
      cadherin neutralizing antibody, inhibits the induction of p27(kip1) and restores
      proliferation in contact-inhibited cells; (vi) re-expression of E-cadherin into
      cells unresponsive to contact inhibition (ARO, FB1) induces a p27(kip1)
      expression and growth arrest. In summary, our data indicate that the altered
      response to contact inhibition exhibited by thyroid anaplastic cancer cells is
      due to the failure to upregulate p27(Kip1) in response to cell-cell interactions.

PMID- 15718254
TI  - Human epidermal keratinocytes undergo (-)-epigallocatechin-3-gallate-dependent
      differentiation but not apoptosis.
AB  - Epigallocatechin-3-gallate (EGCG) is an important chemopreventive agent derived
      from green tea. We recently reported that EGCG treatment enhances keratinocyte
      differentiation as evidenced by increased human involucrin promoter activity
      [Balasubramanian,S., Efimova,T. and Eckert,R.L. (2002) J. Biol. Chem., 277, 1828
      1836]. In the present paper, we extend these findings and show that EGCG also
      increases the expression of other differentiation markers-procaspase 14 and type
      I transglutaminase (TG1). Both TG1 mRNA and protein level, and activity are
      increased by treatment with EGCG. Increased TG1 activity is evidenced by a direct
      transglutaminase assay, and by the ability of EGCG to stimulate the covalent
      incorporation of fluorescein cadaverine substrate into crosslinked intracellular
      structures. In contrast, type II transglutaminase levels are not altered by EGCG
      treatment. We also assessed whether EGCG promotes keratinocyte apoptosis. We show
      that EGCG treatment does not promote the cleavage of procaspase-3, -8, -9 or
      poly(ADP-ribose) polymerase. Moreover, treatment with the pan-caspase inhibitor,
      Z-VAD-FMK, does not reverse the EGCG-associated reduction in cell viability. In
      addition, there is no increase in cells having sub-G(1)/S DNA content, and no
      evidence for the release of cytochrome c from the mitochondria. These findings
      confirm, using several endpoints, that EGCG treatment enhances normal
      keratinocyte differentiation but does not promote apoptosis.

PMID- 15718253
TI  - 22-Oxa-1alpha,25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung
      cancer.
AB  - 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25-D(3)) has potent antiproliferative and
      anti-invasive properties in vitro in cancer cells. However, its calcemic effect
      in vivo limits its therapeutic applications. Here, we report the efficacy of 22
      oxa-1alpha,25-dihydroxyvitamin D(3) (22-oxa-1alpha,25-D(3)), a low calcemic
      analog of vitamin D, against the development of metastatic lung carcinoma after
      an intravenous injection of green fluorescent protein-transfected Lewis lung
      carcinoma (LLC-GFP) cells in C57BL/6 mice. The mice injected with tumor cells
      were implanted simultaneously with osmotic minipumps containing either 1alpha,25
      D(3), 22-oxa-1alpha,25-D(3) or vehicle. The 1alpha,25-D(3) treatment group had
      been hypercalcemic, but the 22-oxa-1alpha,25-D(3) and vehicle treatment groups
      remained normocalcemic for the duration of the experiment. The total number of
      lung metastases, lung weight and the expression of GFP mRNA in the lung were
      markedly decreased in 1alpha,25-D(3) and 22-oxa-1alpha,25-D(3)-treated mice. In
      the in vitro experiment, 1alpha,25-D(3) and 22-oxa-1alpha,25-D(3) reduced the
      expression of matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial
      growth factor and parathyroid hormone-related protein in LLC-GFP cells.
      Furthermore, in the angiogenesis assay, the number of tumor cells or basic
      fibroblast growth factor-induced angiogenesis was reduced in 1alpha,25-D(3) and
      22-oxa-1alpha,25-D(3)-treated mice. Moreover, using a new experimental model of
      vitamin D receptor (VDR) null mutant (VDR(-/-)) mice with corrected hypocalcemia
      and hypervitaminosis D, we examine the anti-cancer effect of 22-oxa-1alpha,25
      D(3) without other functions induced by 22-oxa-1alpha,25-D(3) in the host. In the
      VDR(-/-) mice, 22-oxa-1alpha,25-D(3) directly inhibited the metastatic activity
      of LLC-GFP cells in a dose-dependent manner without exerting a direct influence
      on the calcemic activity or other actions regulated by 22-oxa-1alpha,25-D(3) in
      the host. These results indicate that the inhibition of metastasis and
      angiogenesis-inducing activity in cancer cells seemed to be a major mechanism
      responsible for the anti-cancer effects of 22-oxa-1alpha,25-D(3). Our findings
      show that 22-oxa-1alpha,25-D(3) is beneficial for the prevention of metastasis in
      lung carcinoma.

PMID- 15718255
TI  - Geranylgeraniol and beta-ionone inhibit hepatic preneoplastic lesions, cell
      proliferation, total plasma cholesterol and DNA damage during the initial phases
      of hepatocarcinogenesis, but only the former inhibits NF-kappaB activation.
AB  - Chemopreventive activities of the isoprenoids geranylgeraniol (GGO) and beta
      ionone (BI) were evaluated during initial phases of hepatocarcinogenesis. Rats
      received 8 or 16 mg/100 g body wt GGO (GGO8 and GGO16 groups) or BI (BI8 and BI16
      groups), or only corn oil (CO group, controls) daily for 7 weeks. Incidence (%)
      and the mean number of visible hepatocyte nodules/animal were inhibited in the
      GGO8 (64% and 21 +/- 40), GGO16 (33% and 3 +/- 5), BI8 (50% and 13 +/- 34) and
      BI16 (42% and 9 +/- 19) groups compared with the CO group (100% and 34 +/- 51) (P
      < 0.05, except for the GGO8 group). Number/cm(2) liver section, mean area (mm(2))
      and % liver section area occupied by persistent hepatic placental glutathione S
      transferase positive preneoplastic lesions (PNL) were reduced in the GGO8 (11 +/-
      9; 0.26 +/- 0.35; 2.7 +/- 3.0), GGO16 (6 +/- 6; 0.18 +/- 0.16; 0.9 +/- 0.9), BI8
      (9 +/- 5; 0.13 +/- 0.20; 1.1 +/- 1.2) and BI16 (8 +/- 6; 0.08 +/- 0.09; 0.6 +/-
      0.4) groups compared with the CO group (26 +/- 18; 0.29 +/- 0.34; 7.0 +/- 5.5) (P
      < 0.05). GGO16 and BI16 groups showed smaller visible hepatocyte nodules, reduced
      PNL cell proliferation and total plasma cholesterol levels compared with the CO
      group (P < 0.05), but did not show any differences (P > 0.05) in PNL apoptosis.
      DNA damage expressed as comet length (microm) was reduced in the GGO8 (96.7 +/-
      1.5), GGO16 (94.2 +/- 1.5), BI8 (97.1 +/- 1.1) and BI16 (95.1 +/- 1.5) groups
      compared with the CO group (102.1 +/- 1.7) (P < 0.05). In comparison with normal
      animals, the CO group animals showed increased (P < 0.05) nuclear levels of
      nuclear factor kappa B (NF-kappaB) p65 subunit in hepatic cells, which were
      decreased (P < 0.05) in the GGO16 group animals. Anticarcinogenic actions of
      these isoprenoids seem to follow a dose-response relationship. Results indicate
      that GGO and BI could be represented as promising chemopreventive agents against
      hepatocarcinogenesis. Inhibition of cell proliferation and DNA damage seems to be
      important for the anticarcinogenic actions of isoprenoids, while the inhibition
      of NF-kappaB activation seems to be specifically related to GGO actions.

PMID- 15718256
TI  - Risk of multiple squamous cell carcinomas both in the esophagus and the head and
      neck region.
AB  - While multiple squamous cell carcinomas are often observed in the esophagus and
      the head and neck region and confound us about the favorable treatments, the
      reason why some patients are more likely to develop multiple cancers remains
      obscure. We statistically analyzed clinical factors in 203 patients with newly
      diagnosed squamous cell carcinoma, to assess the risk of multiple cancers for the
      establishment of an effective prevention and screening programs. Widespread
      epithelial oncogenic alterations were assessed as multiple lugol-voiding lesions
      (multiple LVL) using lugol chromoendoscopy. Genetic polymorphisms of alcohol
      dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2) were
      identified by PCR-restriction fragment length polymorphism analysis. Forty
      patients had synchronous multiple cancers and the remaining 163 had solitary
      cancer. Presence of multiple LVL was the only independent risk factor for
      multiple cancers [relative risk (RR) = 67; 95%CI, 15-310]. Multiple LVL was
      observed in only smoking drinkers. Among them, a multivariate analysis
      demonstrated that the ALDH2 deficiency allele (RR = 5.7; 95%CI, 2.8-11.6) and the
      slow metabolizing ADH3 allele (RR = 1.9; 95%CI, 1.1-7.9) were the independent
      risk factors for multiple LVL. Combination of these alleles lead to increase the
      risk of multiple LVL. In conclusion, an episode of multiple LVL is a remarkable
      high risk for multiple cancers both at the esophagus and the head and neck
      region. The interaction between drinking and the ALDH2 deficiency allele
      increases the risk. In addition, the slow metabolizing ADH3 allele enhances the
      risk. Prohibiting the use of alcohol and early detection of cancer are strongly
      recommended for such individuals.

PMID- 15718257
TI  - Reactive oxygen species reduce myofibrillar Ca2+ sensitivity in fatiguing mouse
      skeletal muscle at 37 degrees C.
AB  - The mechanisms of muscle fatigue were studied in small muscle bundles and single
      fibres isolated from the flexor digitorum brevis of the mouse. Fatigue caused by
      repeated isometric tetani was accelerated at body temperature (37 degrees C) when
      compared to room temperature (22 degrees C). The membrane-permeant reactive
      oxygen species (ROS) scavenger, Tiron (5 mM), had no effect on the rate of
      fatigue at 22 degrees C but slowed the rate of fatigue at 37 degrees C to that
      observed at 22 degrees C. Single fibres were microinjected with indo-1 to measure
      intracellular calcium. In the accelerated fatigue at 37 degrees C the tetanic
      [Ca2+](i) did not change significantly and the decline of maximum Ca2+-activated
      force was similar to that observed at 22 degrees C. The cause of the greater rate
      of fatigue at 37 degrees C was a large fall in myofibrillar Ca2+ sensitivity. In
      the presence of Tiron, the large fall in Ca2+ sensitivity was abolished and the
      usual decline in tetanic [Ca2+](i) was observed. This study confirms the
      importance of ROS in fatigue at 37 degrees C and shows that the mechanism of
      action of ROS is a decline in myofibrillar Ca2+ sensitivity.

PMID- 15718258
TI  - Arginine-glycine-aspartic acid (RGD)-containing peptides inhibit the force
      production of mouse papillary muscle bundles via alpha 5 beta 1 integrin.
AB  - Integrins are considered to be an important mechanosensor in cardiac myocytes. To
      test whether integrins can influence cardiac contractile function, the force
      frequency relationships of mouse papillary muscle bundles were measured in the
      presence or absence of a synthetic integrin-binding peptide, GRGDNP (gly-arg-gly
      asp-asn-pro). Results demonstrate that in the presence of an arginine-glycine
      aspartic acid (RGD)-containing synthetic peptide, contractile force was depressed
      significantly by, 28% at 4 Hz, 37.7% at 5 Hz and 20% at 10 Hz (n = 6, P < 0.01).
      Treatment of myofibres with either protease-generated fragments of denatured
      collagen (Type I) or denatured collagen that contain the RGD motif, also reduced
      force production significantly. An integrin-activating antibody for beta(1)
      integrin inhibited the force similar to synthetic RGD peptide. Function-blocking
      integrin antibodies for alpha(5) and beta(1) integrins reversed the effect of the
      RGD-containing peptide, and alpha(5) integrin also reversed the effect of
      proteolytic fragments of denatured collagen on contractile force, whereas
      experiments with function-blocking antibody for beta(3) integrin did not reverse
      the effect of RGD peptide. Force-[Ca(2)(+)](i) measurements showed that the
      depressed rate of force generation observed in the presence of the RGD-containing
      peptide was associated with reduced [Ca(2)(+)](i). Data analyses further
      demonstrated that force per unit of Ca(2)(+) was reduced, suggesting that the
      myofilament activation process was altered. In addition, inhibition of PKC enzyme
      using the selective, cell-permeable inhibitor Ro-32-0432, reversed the activity
      of RGD peptide on papillary muscle bundles. In conclusion, these data indicate
      that RGD peptide, acting via alpha(5)beta(1) integrin, depresses the force
      production from papillary muscle bundles, partly associated with changes in
      [Ca(2)(+)](i) and the myofilament activation processes, that is modulated by
      PKCepsilon.

PMID- 15718259
TI  - Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+
      concentration in the regulation of vascular permeability in Rana in vivo.
AB  - Vascular permeability is assumed to be regulated by the cytosolic Ca(2+)
      concentration ([Ca(2+)](c)) of the endothelial cells. When permeability is
      increased, however, the maximum [Ca(2+)](c) appears to occur after the maximum
      permeability increase, suggesting that Ca(2+)-dependent mechanisms other than the
      absolute Ca(2+) concentration may regulate permeability. Here we investigate
      whether the rate of increase of the [Ca(2+)](c) (d[Ca(2+)](c)/dt) may more
      closely approximate the time course of the permeability increase. Hydraulic
      conductivity (L(p)) and endothelial [Ca(2+)](c) were measured in single perfused
      frog mesenteric microvessels in vivo. The relationships between the time courses
      of the increased L(p), [Ca(2+)](c) and d[Ca(2+)](c)/dt were examined. L(p) peaked
      significantly earlier than [Ca(2+)](c) in all drug treatments examined (Ca(2+)
      store release, store-mediated Ca(2+) influx, and store-independent Ca(2+)
      influx). When L(p) was increased in a store-dependent manner the time taken for
      L(p) to peak (3.6 +/- 0.9 min during store release, 1.2 +/- 0.3 min during store
      mediated Ca(2+) influx) was significantly less than the time taken for
      [Ca(2+)](c) to peak (9.2 +/- 2.8 min during store release, 2.1 +/- 0.7 min during
      store-mediated influx), but very similar to that for the peak d[Ca(2+)](c)/dt to
      occur (4.3 +/- 2.0 min during store release, 1.1 +/- 0.5 min during Ca(2+)
      influx). Additionally, when the increase was independent of intracellular Ca(2+)
      stores, L(p) (0.38 +/- 0.03 min) and d[Ca(2+)](c)/dt (0.30 +/- 0.1 min) both
      peaked significantly before the [Ca(2+)](c) (1.05 +/- 0.31 min). These data
      suggest that the regulation of vascular permeability by endothelial cell Ca(2+)
      may be regulated by the rate of change of the [Ca(2+)](c) rather than the global
      [Ca(2+)].

PMID- 15718260
TI  - Effects of atrial natriuretic peptide on the extrasplenic microvasculature and
      lymphatics in the rat in vivo.
AB  - We developed a novel model using fluorescent intravital microscopy to study the
      effect of atrial natriuretic peptide (ANP) on the extrasplenic microcirculation.
      Continuous infusion of ANP into the splenic artery (10 ng min(-1) for 60 min) of
      male Long-Evans rats (220-250 g, n = 24) induced constriction of the splenic
      arterioles after 15 min (-7.2 +/- 6.6% from baseline diameter of 96 +/- 18.3
      microm, mean +/- S.E.M.) and venules (-14.4 +/- 4.0% from 249 +/- 25.8 microm; P
      < 0.05). At the same time flow did not change in the arterioles (from 1.58 +/-
      0.34 to 1.27 +/- 0.27 ml min(-1)), although it decreased in venules (from 1.67 +/
      0.23 to 1.15 +/- 0.20 ml min(-1)) and increased in the lymphatics (from 0.007 +/
      0.001 to 0.034 +/- 0.008 ml min(-1); P < 0.05). There was no significant change
      in mean arterial pressure (from 118 +/- 5 to 112 +/- 5 mmHg). After continuous
      ANP infusion for 60 min, the arterioles were dilated (108 +/- 16 microm, P <
      0.05) but the venules remained constricted (223 +/- 24 microm). Blood flow
      decreased in both arterioles (0.76 +/- 0.12 ml min(-1)) and venules (1.03 +/-
      0.18 ml min(-1); P < 0.05), but was now unchanged from baseline in the lymphatics
      (0.01 +/- 0.001 ml min(-1)). This was accompanied by a significant decrease in
      MAP (104 +/- 5 mmHg; P < 0.05). At 60 min, there was macromolecular leak from the
      lymphatics, as indicated by increased interstitial fluorescein isothiocyanate
      bovine serum albumin fluorescence (grey level: 0 = black; 255 = white; from 55.8
      +/- 7.6 to 71.8 +/- 5.9, P < 0.05). This study confirms our previous proposition
      that, in the extrasplenic microcirculation, ANP causes greater increases in post-
      than precapillary resistance, thus increasing intrasplenic capillary hydrostatic
      pressure (P(c)) and fluid efflux into the lymphatic system. Longer-term infusion
      of ANP also increases Pc, but this is accompanied by increased 'permeability' of
      the extrasplenic lymphatics, such that fluid is lost to perivascular third
      spaces.

PMID- 15718261
TI  - 5'AMP activated protein kinase expression in human skeletal muscle: effects of
      strength training and type 2 diabetes.
AB  - Strength training enhances insulin sensitivity and represents an alternative to
      endurance training for patients with type 2 diabetes (T2DM). The 5'AMP-activated
      protein kinase (AMPK) may mediate adaptations in skeletal muscle in response to
      exercise training; however, little is known about adaptations within the AMPK
      system itself. We investigated the effect of strength training and T2DM on the
      isoform expression and the heterotrimeric composition of the AMPK in human
      skeletal muscle. Ten patients with T2DM and seven healthy subjects strength
      trained (T) one leg for 6 weeks, while the other leg remained untrained (UT).
      Muscle biopsies were obtained before and after the training period. Basal AMPK
      activity and protein/mRNA expression of both catalytic (alpha1 and alpha2) and
      regulatory (beta1, beta2, gamma1, gamma2a, gamma2b and gamma3) AMPK isoforms were
      independent of T2DM, whereas the protein content of alpha1 (+16%), beta2 (+14%)
      and gamma1 (+29%) was higher and the gamma3 content was lower (-48%) in trained
      compared with untrained muscle (all P < 0.01). The majority of alpha protein co
      immunoprecipitated with beta2 and alpha2/beta2 accounted for the majority of
      these complexes. gamma3 was only associated with alpha2 and beta2 subunits, and
      accounted for approximately 20% of all alpha2/beta2 complexes. The remaining
      alpha2/beta2 and the alpha1/beta2 complexes were associated with gamma1. The
      trimer composition was unaffected by T2DM, whereas training induced a shift from
      gamma3- to gamma1-containing trimers. The data question muscular AMPK as a
      primary cause of T2DM whereas the maintained function in patients with T2DM makes
      muscular AMPK an obvious therapeutic target. In human skeletal muscle only three
      of 12 possible AMPK trimer combinations exist, and the expression of the subunit
      isoforms is susceptible to moderate strength training, which may influence
      metabolism and improve energy homeostasis in trained muscle.

PMID- 15718262
TI  - Differential expression of heat shock protein 27 and 70 in renal papillary
      collecting duct and interstitial cells - implications for urea resistance.
AB  - The adaptation of renal medullary cells to their hyperosmotic environment
      involves the accumulation of compatible organic osmolytes and the enhanced
      synthesis of heat shock proteins (HSP) 27 and 70. While the mechanisms leading to
      osmolyte accumulation are similar in papillary collecting duct (PCD) and
      papillary interstitial (PI) cells, the present data demonstrate that HSP27 and
      HSP70 are expressed differentially in these cells both in vivo and in vitro.
      HSP70 is abundant in PCD, but not expressed in PI cells in the papilla in situ,
      while HSP27 is expressed in both PCD and PI cells. These observations could be
      reproduced by non-permeant solutes in cultured cells. Osmotic stress strongly
      induced HSP70 in MDCK cells (as a model for PCD cells), but not in PI cells,
      while HSP27 was constitutively expressed in MDCK cells and was up-regulated in PI
      cells. Since prior hypertonic stress (NaCl addition) protects MDCK against
      subsequent exposure to high urea concentrations, this effect was also assessed in
      PI cells. In both cell lines, hypertonic pretreatment prior to urea exposure (400
      mm) strongly attenuated caspase-3 activation. Inhibition of HSP27 expression by
      antisense transfection diminished the protective effect of hypertonic
      preconditioning in PI cells, while attenuation of HSP70 expression in MDCK cells
      diminished the protective effect of hypertonic preconditioning in these cells.
      These observations indicate that PCD and PI cells employ cell-specific mechanisms
      for protection against high urea concentrations as present in the renal papilla
      during antidiuresis.

PMID- 15718263
TI  - Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced
      cardioprotection are sex-dependent in the rat.
AB  - The cardioprotective effects of short-term exercise against myocardial ischaemia
      reperfusion injury in male and female rats were examined. We subjected male and
      female rats to 0 (Sed; n = 8 males and 8 females), 1 (1 day; n = 10 males and 8
      females), or 5 (5 day; n = 6 males and 6 females) days of treadmill running.
      Langendorff-perfused hearts underwent 1 h of regional ischaemia and 2 h of
      reperfusion, and infarct size (expressed as a percentage of the zone at risk;
      ZAR), left ventricular pressure development, and coronary flow were measured for
      each heart. Preischaemic pressure development and coronary flow did not differ
      between the sexes nor were they influenced by exercise. Sed females had
      significantly smaller infarct sizes (25 +/- 3%) than Sed male hearts (37 +/- 3%;
      P < 0.001). Short-term running significantly reduced infarct size following 1 day
      (27 +/- 3%; P < 0.05) and 5 days (30 +/- 4%; P < 0.10) of exercise in males. One
      day of running did not reduce infarct size in females (19 +/- 3%; P = NS), but 5
      day females did show a significant reduction in infarct size (13 +/- 2%; P <
      0.05). There was no relationship between postischaemic coronary vascular
      hyperaemia and infarct size across sexes or exercise training groups. Hearts from
      Sed females exhibited significantly higher manganese superoxide dismutase (MnSOD)
      protein expression than hearts from Sed males, but short-term exercise (neither 1
      nor 5 days) did not alter MnSOD protein in either sex. Increased sarcolemmal ATP
      sensitive K(+) (K(ATP)) channel subunit protein expression (SUR2A and/or
      K(ir)6.2) correlated closely with sex-dependent and exercise-acquired protection
      against myocardial infarction. These data indicate that: (1) sex-dependent and
      exercise-induced differences in the susceptibility of the heart to ischaemia
      reperfusion injury are not associated with improved coronary flow or
      postischaemic hyperaemia; (2) increased MnSOD protein expression is not necessary
      for exercise-induced protection from infarction; and (3) one possible mechanism
      for sex-dependent and exercise-mediated reductions in infarct size involves an
      increased protein expression of cardiac sarcolemmal K(ATP) channels.

PMID- 15718264
TI  - Mechanical activation of rectal intraganglionic laminar endings in the guinea pig
      distal gut.
AB  - The rectum receives specialized extrinsic afferent innervation by stretch
      sensitive, low threshold, slowly adapting mechanoreceptors, with transduction
      sites shown to correspond to rectal intraganglionic laminar endings (IGLEs).
      Rectal IGLEs are located in myenteric ganglia, surrounded by the longitudinal and
      circular smooth muscle layers; in this study we investigated the mechanical
      stimuli to which they respond. Mechanoreceptors had graded responses to highly
      focal transmural compression with von Frey hairs. They were activated when
      stretched circumferentially by imposed increases of both length and load. Under
      both conditions, firing typically occurred in bursts associated with phasic
      muscle contractions. However, many contractions did not evoke firing.
      Longitudinal stretch also evoked firing, again associated with contractile
      activity. Thus, mechanoreceptors did not show directional sensitivity. Two
      agonists that excited smooth muscle directly (0.1 microm [beta-Ala(8)]-neurokinin
      A (4-10) and 1 microm carbachol) activated rectal mechanoreceptors, but not in
      the presence of Ca(2)(+)-free solution or when preparations were kept entirely
      slack. We measured the dimensions, in both longitudinal and circumferential axes,
      of receptive fields during smooth muscle contractile activity, using video
      micrography. Contractile activity within the receptive field often differed
      significantly from the behaviour of the preparation as a whole, providing an
      explanation for many of the discrepancies between gross contractility and firing.
      Simultaneous contraction of both muscle layers within the receptive field was the
      strongest predictor of mechanoreceptor activation. Our results suggest that
      rectal mechanoreceptors do not act simply as tension receptors: rather they
      appear to detect mechanical deformation of myenteric ganglia - especially
      flattening - associated with stretch of the receptive field, or contractions of
      smooth muscle within the receptive field.

PMID- 15718265
TI  - K+ secretion activated by luminal P2Y2 and P2Y4 receptors in mouse colon.
AB  - Extracellular nucleotides are important regulators of epithelial ion transport,
      frequently exerting their action from the luminal side. Luminal P2Y receptors
      have previously been identified in rat distal colonic mucosa. Their activation by
      UTP and ATP stimulates K+ secretion. The aim of this study was to clarify which
      of the P2Y receptor subtypes are responsible for the stimulated K+ secretion. To
      this end P2Y2 and P2Y4 knock-out mice were used to measure distal colonic ion
      transport in an Ussing chamber. In mouse (NMRI) distal colonic mucosa, luminal
      UTP and ATP with similar potency induced a rapid and transient increase of the
      transepithelial voltage (V(te)) (UTP: from -0.81 +/- 0.23 to 3.11 +/- 0.61 mV, n
      = 24), an increase of equivalent short circuit current (I(sc)) by 166.9 +/- 22.8
      microA cm(-2) and a decrease of transepithelial resistance (R(te)) from 29.4 +/-
      2.4 to 23.5 +/- 2.0 Omega cm2. This effect was completely inhibited by luminal
      Ba2+ (5 mm, n = 5) and iberiotoxin (240 nm, n = 6), indicating UTP/ATP-stimulated
      K+ secretion. RT-PCR analysis of isolated colonic crypts revealed P2Y2, P2Y4 and
      P2Y6 specific transcripts. The luminal UTP-stimulated K+ secretion was still
      present in P2Y2 receptor knock-out mice, but significantly reduced (DeltaV(te):
      0.83 +/- 0.26 mV) compared to wild-type littermates (DeltaV(te): 2.08 +/- 0.52
      mV, n = 9). In P2Y4 receptor knock-out mice the UTP-induced K+ secretion was
      similarly reduced. Luminal UTP-stimulated K+ secretion was completely absent in
      P2Y2/P2Y4 double receptor KO mice. Basolateral UTP showed no effect. In summary,
      these results indicate that both the P2Y2 and P2Y4 receptors are present in the
      luminal membrane of mouse distal colonic mucosa, and stimulation of these
      receptors leads to K+ secretion.

PMID- 15718266
TI  - Effects of the mutation R145G in human cardiac troponin I on the kinetics of the
      contraction-relaxation cycle in isolated cardiac myofibrils.
AB  - Familial hypertrophic cardiomyopathy (FHC) has been linked to mutations in
      sarcomeric proteins such as human cardiac troponin I (hcTnI). To elucidate the
      functional consequences of the mutation hcTnI(R145G) on crossbridge kinetics,
      force kinetics were analysed in murine cardiac myofibrils carrying either the
      mutant or the wild-type protein. The mutation was introduced into the myofibrils
      in two different ways: in the first approach, the endogenous Tn was replaced by
      incubation of the myofibrils with an excess of reconstituted recombinant hcTn
      containing either hcTnI(WT) or hcTnI(R145G). Alternatively, myofibrils were
      isolated either from non-transgenic or transgenic mice expressing the
      corresponding mcTnI(R146G) mutation. In myofibrils from both models, the mutation
      leads to a significant upward shift of the passive force-sarcomere length
      relation determined at pCa 7.5. Addition of 5 mm BDM (2,3-butandione-2-monoxime),
      an inhibitor of actomyosin ATPase partially reverses this shift, suggesting that
      the mutation impairs the normal function of cTnI to fully inhibit formation of
      force-generating crossbridges in the absence of Ca(2)(+). Maximum force
      development (F(max)) is significantly decreased by the mutation only in
      myofibrils exchanged with hcTnI(R145G) in vitro. Ca(2)(+) sensitivity of force
      development was reduced by the mutation in myofibrils from transgenic mice but
      not in exchanged myofibrils. In both models the rate constant of force
      development k(ACT) is reduced at maximal [Ca(2)(+)] but not at low [Ca(2)(+)]
      where it is rather increased. Force relaxation is significantly prolonged due to
      a reduction of the relaxation rate constant k(REL). We therefore assume that the
      impairment in the regulatory function of TnI by the mutation leads to modulations
      in crossbridge kinetics that significantly alter the dynamics of myofibrillar
      contraction and relaxation.

PMID- 15718267
TI  - Activation of heteroliganded mouse muscle nicotinic receptors.
AB  - The activation of the mouse muscle-type nicotinic acetylcholine receptor was
      studied in the presence of carbachol, and in the simultaneous presence of
      carbachol and choline. The channel currents were recorded under steady-state
      conditions using cell-attached single-channel patch clamp, and during transient
      exposures to the agonists using a piezo-driven fast application system. The
      presence of choline resulted in inhibition of currents elicited by carbachol. The
      inhibitory effect of choline manifested as a reduction in the effective opening
      rate (increase in the mean intracluster closed time duration) in single-channel
      recordings. In the fast application experiments, the peak current amplitude was
      reduced and the current rise time increased when choline was co-applied with
      carbachol. The data were analysed according to a model in which receptor
      interactions with carbachol and choline resulted in three types of ligation:
      receptors occupied by two carbachol molecules, receptors occupied by two choline
      molecules, and receptors in which one agonist binding site was occupied by
      carbachol and the other by choline, i.e. heteroliganded receptors. All three
      agonist-bound receptor populations could open albeit with different efficacies.
      The affinity of the resting receptor to choline was estimated to be 1-2 mm, and
      heteroliganded receptors opened with an opening rate constant of approximately
      3000 s(-1). The results of the analysis suggest that the presence of choline in
      the neuromuscular junction in vivo has little effect on the time course of
      synaptic currents. Nevertheless, the contribution of heteroliganded receptors
      should be taken into consideration when the receptor is exposed simultaneously to
      two or more agonists.

PMID- 15718268
TI  - Betamethasone effects on fetal sheep cerebral blood flow are not dependent on
      maturation of cerebrovascular system and pituitary-adrenal axis.
AB  - Synthetic glucocorticoids are administered to pregnant women in premature labour
      to accelerate fetal lung maturation at a time when fetal cerebrovascular and
      endocrine systems are maturing. Exposure to glucocorticoids at 0.8-0.9 of
      gestation increases peripheral and cerebrovascular resistance (CVR) in fetal
      sheep. We examined whether the increase of CVR and its adverse effect on cerebral
      blood flow (CBF) depend on the current level of maturation of the pituitary
      adrenal axis and the cerebrovascular system. Using fluorescent microspheres,
      regional CBF was measured in 11 brain regions before and 24 h and 48 h after the
      start of 3.3 microg kg(-1) h(-1) betamethasone (n = 8) or vehicle (n = 7)
      infusions to fetal sheep at 0.73 of gestation. Hypercapnic challenges were
      performed before and 24 h after the onset of betamethasone exposure to examine
      betamethasone effects on cerebrovascular reactivity. Betamethasone exposure
      decreased CBF by approximately 40% in all brain regions after 24 h of infusion (P
      < 0.05). The decline in CBF was mediated by a CVR increase of 111 +/- 16% in the
      cerebral cortex and 129 +/- 29% in subcortical regions (P < 0.05). Hypercapnic
      cerebral vasodilatation and associated increase in CBF were blunted (P < 0.05).
      Fetal CBF recovered after 48 h of betamethasone administration. There were no
      differences in glucocorticoid induced CBF and CVR changes compared with our
      previous findings at 0.87 of gestation. We conclude that the cerebrovascular
      effects of antenatal glucocorticoids are independent of cerebrovascular
      maturation and preparturient increase in activity of the fetal pituitary-adrenal
      axis.

PMID- 15718269
TI  - Effects of lorazepam on short latency afferent inhibition and short latency
      intracortical inhibition in humans.
AB  - Experimental studies have demonstrated that the GABAergic system modulates
      acetylcholine release and, through GABA(A) receptors, tonically inhibits
      cholinergic activity. Little is known about the effects of GABA on the
      cholinergic activity in the human central nervous system. In vivo evaluation of
      some cholinergic circuits of the human brain has recently been introduced using a
      transcranial magnetic stimulation (TMS) protocol based on coupling peripheral
      nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an
      inhibitory effect on motor cortex excitability at short intervals (short latency
      afferent inhibition, SAI). We investigated whether GABA(A) activity enhancement
      by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on
      a different TMS protocol of cortical inhibition, the short interval intracortical
      inhibition (SICI), which is believed to be directly related to GABA(A) activity.
      In 10 healthy volunteers, the effects of lorazepam were compared with those
      produced by quetiapine, a psychotropic drug with sedative effects with no
      appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and
      with those of a placebo using a randomized double-blind study design.
      Administration of lorazepam produced a significant increase in SICI (F(3,9) =
      3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam
      (F(3,9) = 9.39, P = 0.0002). Our findings demonstrate that GABA(A) activity
      enhancement determines a suppression of SAI and an increase of SICI.

PMID- 15718270
TI  - Functional expression of beta-chemokine receptors in osteoblasts: role of
      regulated upon activation, normal T cell expressed and secreted (RANTES) in
      osteoblasts and regulation of its secretion by osteoblasts and osteoclasts.
AB  - The expression and functions of receptors for the beta-chemokine, regulated upon
      activation, normal T cell expressed, and secreted (RANTES)/CCL5, were
      investigated in osteoblasts. Both primary osteoblasts and the MC3T3-E1 osteoblast
      cell line express the RANTES receptors, CCR1, 3, 4, and 5 (by RT-PCR), which
      encode functional receptors in osteoblasts as shown by [125I]-RANTES binding
      followed by Scatchard analysis. Expression of all four RANTES receptor mRNAs in
      osteoblast is in contrast to the reports of expression of CCR1 being the only
      RANTES receptor expressed by osteoclasts. Exogenous RANTES elicits chemotaxis of
      osteoblasts and promotes cell survival via phosphatidylinositol 3-kinase with
      attendant phosphorylation of Akt. Osteoclastic RANTES, obtained from the
      conditioned medium of receptor activator of nuclear factor-kappa B ligand
      differentiated RAW264.7 cells also induces chemotaxis of MC3T3-E1 cells.
      Incubating the conditioned medium with an anti-RANTES neutralizing antibody
      attenuated this effect. RANTES secretion from osteoblast is inhibited by
      differentiation promoting hormones, e.g. 1,25 (OH)2D3 and dexamethasone, whereas
      macrophage inflammatory protein-1 alpha (but not macrophage inflammatory protein
      1 beta) and elevated calcium induce it. Elevated calcium also stimulated RANTES
      secretion by osteoclasts. Therefore, RANTES is an osteoblast chemoattractant and
      a survival-promoting molecule whose regulation in osteoblast is varied.
      Furthermore, RANTES secreted from osteoclasts induces osteoblast chemotaxis.
      Therefore, expression of RANTES and its receptors in both osteoblasts and
      osteoclasts could enable this chemokine to act in autocrine/paracrine modes.

PMID- 15718271
TI  - Identification of the salmon somatolactin receptor, a new member of the cytokine
      receptor family.
AB  - Somatolactin (SL) is a pituitary hormone of the GH/prolactin (PRL) family that so
      far has been found only in fish. Compared with GH and PRL, the primary structure
      of SL is highly conserved among divergent fish species, suggesting it has an
      important function and a discriminating receptor that constrains structural
      change. However, SL functions are poorly understood, and receptors for SL have
      not yet been identified. During cloning of GH receptor cDNA from salmon, we found
      a variant with relatively high (38-58%) sequence identity to vertebrate GH
      receptors and low (28-33%) identity to PRL receptors; however, the recombinant
      protein encoding the extracellular domain showed only weak binding of GH. Ligand
      binding of the recombinant extracellular domain for this receptor confirmed that
      the cDNA encoded a specific receptor for SL. The SL receptor (SLR) has common
      features of a GH receptor including FGEFS motif, six cysteine residues in the
      extracellular domain, a single transmembrane region, and Box 1 and 2 regions in
      the intracellular domain. These structural characteristics place the SLR in the
      cytokine receptor type I homodimeric group, which includes receptors for GH, PRL,
      erythropoietin, thrombopoietin, granulocyte-colony stimulating factor, and
      leptin. Transcripts for SLR were found in 11 tissues with highest levels in liver
      and fat, supporting the notion that a major function of SL is regulation of lipid
      metabolism. Cloning SLR cDNA opens the way for discovery of new SL functions and
      target tissues in fish, and perhaps novel members of this receptor family in
      other vertebrates.

PMID- 15718273
TI  - The remarkable conservation of corticotropin-releasing hormone (CRH)-binding
      protein in the honeybee (Apis mellifera) dates the CRH system to a common
      ancestor of insects and vertebrates.
AB  - CRH-binding protein (CRH-BP) is a key factor in the regulation of CRH signaling;
      it modulates the bioactivity and bioavailability of CRH and its related peptides.
      The conservation of CRH-BP throughout vertebrates was only recently demonstrated.
      Here we report the presence of CRH-BP in the honeybee (Apis mellifera) and other
      insects. Honeybee CRH-BP resembles previously characterized vertebrate CRH-BP
      sequences with respect to conserved cysteine residues, gene organization, and
      overall sequence identity. Phylogenetic analyses confirm the unambiguous
      orthology of insect and vertebrate CRH-BP sequences. Soon after their discovery,
      it was noted that insect diuretic hormone-I (DH-I) and its receptor share
      similarities with the vertebrate CRH family and their receptors. Despite these
      similarities, demonstration of common ancestry of DH-I and the vertebrate CRH
      family is still speculative: the mature neuropeptides are short, and their genes
      differ substantially with regard to the number of coding exons. Moreover, DH and
      CRH receptors belong to the much larger family of G protein-coupled receptors. In
      contrast, the unique and conspicuous features of CRH-BP greatly facilitate the
      establishment of orthology over much larger evolutionary distances. The
      identification of CRH-BP in insects clearly indicates that this gene predates
      vertebrates by at least several hundred million years. Moreover, our findings
      imply that a CRH system is shared by insects and vertebrates alike and,
      consequently, that it has been present at least since the common ancestor to both
      phylogenetic lines of proto- and deuterostomians.

PMID- 15718272
TI  - Stimulation of human trophoblast invasion by placental growth hormone.
AB  - A critical step in establishment of human pregnancy is the invasion of the uterus
      wall by the extravillous cytotrophoblast (EVCT), a process regulated by multiple
      autocrine and paracrine factors. Hormones belonging to the GH/prolactin family
      are expressed at the maternofetal interface. Because they are involved in cell
      motility in various models, we examined the possible regulatory role of human
      placental GH (hPGH) in EVCT invasiveness. By using an in vitro invasion model, we
      found that EVCT isolated from first-trimester chorionic villi and cultured on
      Matrigel secreted hPGH and expressed human GH receptor (hGHR). These data were
      confirmed by in situ immunohistochemistry. EVCT expressed the full-length and
      truncated forms of hGHR, and the Janus kinase-2/signal transducer and activator
      of transcription factor-5 signaling pathway was activated in EVCT by hPGH
      treatment. Strong hPGH and hGHR expression was observed when EVCT invaded
      Matrigel and moved through the pores of the filter on which they were cultured.
      hPGH stimulated EVCT invasiveness, and this effect was inhibited by a Janus
      kinase-2 inhibitor. Interestingly, hPGH was more efficient than pituitary GH in
      stimulating EVCT invasiveness. These results offer the first evidence for a
      placental role of hPGH and suggest an autocrine/paracrine role of hPGH in the
      regulation of trophoblast invasion.

PMID- 15718274
TI  - Insulin receptor substrate-1 is required for bone anabolic function of
      parathyroid hormone in mice.
AB  - Bone anabolic action of PTH has been suggested to be mediated by induction of IGF
      I in osteoblasts; however, little is known about the molecular mechanism by which
      IGF-I leads to bone formation under the PTH stimulation. This study initially
      confirmed in mouse osteoblast cultures that PTH treatment increased IGF-I mRNA
      and protein levels and alkaline phosphatase activity, which were accompanied by
      phosphorylations of IGF-I receptor, insulin receptor substrate (IRS)-1 and IRS-2,
      essential adaptor molecules for the IGF-I signaling. To learn the involvement of
      IRS-1 and IRS-2 in the bone anabolic action of PTH in vivo, IRS-1-/- and IRS-2-/-
      mice and their respective wild-type littermates were given daily injections of
      PTH (80 mug/kg) or vehicle for 4 wk. In the wild-type mice, the PTH injection
      increased bone mineral densities of the femur, tibia, and vertebrae by 10-20%
      without altering the serum IGF-I level. These stimulations were similarly seen in
      IRS-2-/- mice; however, they were markedly suppressed in IRS-1-/- mice. Although
      the PTH anabolic effects were stronger on trabecular bones than on cortical
      bones, the stimulations on both bones were blocked in IRS-1-/- mice but not in
      IRS-2-/- mice. Histomorphometric and biochemical analyses showed an increased
      bone turnover by PTH, which was also blunted by the IRS-1 deficiency, though not
      by the IRS-2 deficiency. These results indicate that the PTH bone anabolic action
      is mediated by the activation of IRS-1, but not IRS-2, as a downstream signaling
      of IGF-I that acts locally as an autocrine/paracrine factor.

PMID- 15718276
TI  - Proopiomelanocortin processing in the anterior pituitary of the ovine fetus after
      lesion of the hypothalamic paraventricular nucleus.
AB  - The hypothalamic-pituitary-adrenocortical axis plays an essential role in the
      maturation of fetal organs and, in sheep, birth. Lesioning the paraventricular
      nucleus (PVN) in fetal sheep prevents adrenocortical maturation and parturition
      without altering plasma immunoreactive ACTH concentrations. The purpose of this
      study was to determine the effect of PVN lesion on anterior pituitary processing
      of proopiomelanocortin (POMC) to ACTH, plasma concentrations of ACTH and ACTH
      precursors (POMC; 22-kDa proACTH), and expression of subtilisin-like prohormone
      convertase 3 (SPC3) in corticotropes in fetal sheep. PVN lesion did not affect
      anterior pituitary POMC and 22-kDa proACTH levels, whereas ACTH was significantly
      affected. The ACTH precursor (POMC plus 22-kDa proACTH) to ACTH ratio in the
      anterior pituitary was significantly increased after PVN lesion. Post-PVN lesion,
      fetal plasma ACTH(1-39), was below the limit of detection, whereas ACTH
      precursors (POMC plus 22-kDa proACTH) were not affected. In the inferior region
      of the anterior pituitary, 40-50% of corticotropes had detectable SPC3
      hybridization signal, and PVN lesion did not change the extent of colocalization
      of POMC and SPC3, or SPC3 mRNA levels within corticotropes. Neither the percent
      of corticotropes in the superior region containing SPC3 hybridization (7-12%) or
      hybridization signal strength was altered in response to PVN lesion. In
      conclusion, the fetal PVN is necessary for sustaining adequate anterior pituitary
      processing of POMC to ACTH and ACTH release needed for maturing the adrenal
      cortex in the sheep fetus.

PMID- 15718275
TI  - Maternal diabetes adversely affects preovulatory oocyte maturation, development,
      and granulosa cell apoptosis.
AB  - Maternal diabetes adversely affects preimplantation embryo development and
      pregnancy outcomes. The objective of this study was to determine whether diabetes
      has an impact at an earlier stage of development, the preovulatory oocyte. Models
      of both acute and chronic insulin-dependent diabetes were used. Acute
      hyperglycemia was induced by a single streptozotocin injection. Akita mice, which
      harbor an autosomal dominant mutation causing them to be chronically
      hypoinsulinemic and hyperglycemic, were used. In both models, preovulatory
      oocytes were markedly smaller when compared with control animals. A significantly
      greater number of control oocytes had progressed to meiotic maturation before
      diabetic oocytes. Both models were found to have smaller, less developed ovarian
      follicles with a greater number of apoptotic foci by histological evaluation as
      well as by terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end labeling staining. Immunohistochemistry displayed a greater
      amount of TNF-related apoptosis-inducing ligand (TRAIL) and KILLER, a key murine
      ligand and receptor involved in the extrinsic pathway, expressed in cumulus cells
      from hyperglycemic mice compared with controls, suggesting that this apoptotic
      pathway may be up-regulated under diabetic stress. Elevated KILLER expression was
      also confirmed through Western blotting. Connexin-43 expression was found to be
      lower by immunohistochemistry and Western blot analysis in the diabetic samples.
      Both models of maternal hyperglycemia and hypoinsulinemia may have a detrimental
      effect on oocyte maturation and development as detailed by the smaller sizes of
      oocytes and developing ovarian follicles, the lowered percentage reaching
      germinal vesicle breakdown, and the greater amount of apoptosis. In addition,
      there may be dysfunctional or decreased communication in diabetic oocytes, as
      demonstrated by lower expression of connexin-43.

PMID- 15718277
TI  - Role of the second-messenger cyclic-adenosine 5'-diphosphate-ribose on
      adrenocorticotropin secretion from pituitary cells.
AB  - We examined the role of the second-messenger cyclic-ADP-ribose (cADPR) on the
      regulation of ACTH secretion using AtT20 corticotroph tumor cell line. We found
      that the cADPR antagonist, 8-Br-cADPR, substantially diminished the secretion of
      ACTH induced by CRH and potassium in these cells, whereas xestospongin C, an
      inositol 1,4,5-triphosphate receptor antagonist, had no effect. In addition, the
      cADPR agonist, 3-deaza-cADPR, augmented ACTH secretion. The presence of the
      components of the cADPR system, namely ryanodine receptor, CD38, and cADPR
      itself, was determined in AtT20 cells. Furthermore, we observed that antagonists
      of the ryanodine channel and cADPR system can decrease the potassium-induced Ca2+
      transients in these cells. These results suggest that cADPR is a second messenger
      in pituitary cells and regulates ACTH secretion by a mechanism dependent on
      activation of the ryanodine channel by extracellular Ca2+.

PMID- 15718278
TI  - Calcium-sensing receptor expression in human adipocytes.
AB  - The presence of the extracellular calcium-sensing receptor (CaSR) has been
      demonstrated in numerous cells that are key in the control of serum calcium
      concentrations, underscoring its relevance in systemic calcium homeostasis. The
      more recent evidence of its presence in tissues not involved in this function has
      broadened the spectrum of interest in this protein, now known to regulate diverse
      cell functions such as proliferation, differentiation, and apoptosis. This study
      shows the expression of CaSR in human omental adipose tissue, isolated
      adipocytes, and adipocyte progenitor cells as assessed by RT-PCR and
      immunoblotting. This is the first report of CaSR being expressed in human
      adipocytes and adipocyte progenitor cells, opening the possibility to investigate
      the physiological implications and thus contributing a novel component for
      adipose tissue biology research.

PMID- 15718279
TI  - The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in
      rats.
AB  - Peptide YY (PYY), an anorectic peptide, is secreted postprandially from the
      distal gastrointestinal tract. PYY(3-36), the major form of circulating PYY,
      binds to the hypothalamic neuropeptide Y Y2 receptor (Y2-R) with a high-affinity,
      reducing food intake in rodents and humans. Additional gastrointestinal hormones
      involved in feeding, including cholecystokinin, glucagon-like peptide 1, and
      ghrelin, transmit satiety or hunger signals to the brain via the vagal afferent
      nerve and/or the blood stream. Here we determined the role of the afferent vagus
      nerve in PYY function. Abdominal vagotomy abolished the anorectic effect of PYY(3
      36) in rats. Peripheral administration of PYY(3-36) induced Fos expression in the
      arcuate nucleus of sham-operated rats but not vagotomized rats. We showed that Y2
      R is synthesized in the rat nodose ganglion and transported to the vagal afferent
      terminals. PYY(3-36) stimulated firing of the gastric vagal afferent nerve when
      administered iv. Considering that Y2-R is present in the vagal afferent fibers,
      PYY(3-36) could directly alter the firing rate of the vagal afferent nerve via Y2
      R. We also investigated the effect of ascending fibers from the nucleus of the
      solitary tract on the transmission of PYY(3-36)-mediated satiety signals. In
      rats, bilateral midbrain transections rostral to the nucleus of the solitary
      tract also abolished PYY(3-36)-induced reductions in feeding. This study
      indicates that peripheral PYY(3-36) may transmit satiety signals to the brain in
      part via the vagal afferent pathway.

PMID- 15718280
TI  - Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the
      fetal-maternal interface.
AB  - HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule
      that is primarily expressed at the fetal-maternal interface, where it is thought
      to play a role in protecting the fetus from the maternal immune response. HLA-G
      binds a limited repertoire of peptides and interacts with the inhibitory
      leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural
      killer cell receptors. To gain further insights into HLA-G function, we
      determined the 1.9-A structure of a monomeric HLA-G complexed to a natural
      endogenous peptide ligand from histone H2A (RIIPRHLQL). An extensive network of
      contacts between the peptide and the antigen-binding cleft reveal a constrained
      mode of binding reminiscent of the nonclassical HLA-E molecule, thereby providing
      a structural basis for the limited peptide repertoire of HLA-G. The alpha3 domain
      of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is
      structurally distinct from the alpha3 domains of classical MHC-I molecules,
      providing a rationale for the observed affinity differences for these ligands.
      The structural data suggest a head-to-tail mode of dimerization, mediated by an
      intermolecular disulfide bond, that is consistent with the observation of HLA-G
      dimers on the cell surface.

PMID- 15718281
TI  - DNA twisting flexibility and the formation of sharply looped protein-DNA
      complexes.
AB  - Gene-regulatory complexes often require that pairs of DNA-bound proteins interact
      by looping-out short (often approximately 100-bp) stretches of DNA. The loops can
      vary in detailed length and sequence and, thus, in total helical twist, which
      radically alters their geometry. How this variability is accommodated
      structurally is not known. Here we show that the inherent twistability of 89- to
      105-bp DNA circles exceeds theoretical expectation by up to 400-fold. These
      results can be explained only by greatly enhanced DNA flexibility, not by
      permanent bends. They invalidate the use of classic theories of flexibility for
      understanding sharp DNA looping but support predictions of two recent theories.
      Our findings imply an active role for DNA flexibility in loop formation and
      suggest that variability in the detailed helical twist of regulatory loops is
      accommodated naturally by the inherent twistability of the DNA.

PMID- 15718282
TI  - Comparative sequencing provides insights about the structure and conservation of
      marsupial and monotreme genomes.
AB  - Sequencing and comparative analyses of genomes from multiple vertebrates are
      providing insights about the genetic basis for biological diversity. To date,
      these efforts largely have focused on eutherian mammals, chicken, and fish. In
      this article, we describe the generation and study of genomic sequences from
      noneutherian mammals, a group of species occupying unusual phylogenetic
      positions. A large sequence data set (totaling >5 Mb) was generated for the same
      orthologous region in three marsupial (North American opossum, South American
      opossum, and Australian tammar wallaby) and one monotreme (platypus) genomes.
      These ancient mammalian genomes are characterized by unusual architectural
      features with respect to G + C and repeat content, as well as compression
      relative to human. Approximately 14% and 34% of the human sequence forms
      alignments with the orthologous sequence from platypus and the marsupials,
      respectively; these numbers are distinctly lower than that observed with
      nonprimate eutherian mammals (45-70%). The alignable sequences between human and
      each marsupial species are not completely overlapping (only 80% common to all
      three species) nor are the platypus-alignable sequences completely contained
      within the marsupial-alignable sequences. Phylogenetic analysis of synonymous
      coding positions reveals that platypus has a notably long branch length, with the
      human-platypus substitution rate being on average 55% greater than that seen with
      human-marsupial pairs. Finally, analyses of the major mammalian lineages reveal
      distinct patterns with respect to the common presence of evolutionarily conserved
      vertebrate sequences. Our results confirm that genomic sequence from noneutherian
      mammals can contribute uniquely to unraveling the functional and evolutionary
      histories of the mammalian genome.

PMID- 15718283
TI  - Probing site-specific conformational distributions in protein folding with solid
      state NMR.
AB  - We demonstrate an experimental approach to structural studies of unfolded and
      partially folded proteins in which conformational distributions are probed at a
      site-specific level by 2D solid-state 13C NMR spectroscopy of glassy frozen
      solutions. Experiments on chemical denaturation of the 35-residue villin
      headpiece subdomain, a model three-helix-bundle protein with a known folded
      structure, reveal that 13C-labeled residues in the three helical segments of the
      folded state have markedly different conformational distributions in the unfolded
      state. Moreover, the 2D solid-state NMR line shapes near the unfolding midpoint
      do not fit a simple two-state model, in which the conformational distributions of
      the unfolded component are assumed to be independent of denaturant concentration.
      Comparison with solid-state NMR spectra of peptides containing the individual
      helical segments suggests an alternative two-step description of conformational
      distributions in partially folded states of the helical villin headpiece
      subdomain, in which chemical denaturation is viewed as a disruption of tertiary
      contacts followed by equilibration of local secondary structure according to the
      intrinsic helical propensities of individual segments.

PMID- 15718284
TI  - beta-Arrestin2, interacting with phosphodiesterase 4, regulates synaptic release
      probability and presynaptic inhibition by opioids.
AB  - Most mu-opioid receptor agonists recruit beta-arrestin2, with some exceptions
      such as morphine. Surprisingly, however, the acute analgesic effect of morphine
      is enhanced in the absence of beta-arrestin2. To resolve this paradox, we
      examined the effects of morphine and fentanyl in acute brain slices of the locus
      coeruleus and the periaqueductal gray from beta-arrestin2 knockout mice. We
      report that, in these mice, presynaptic inhibition of evoked inhibitory
      postsynaptic currents was enhanced, whereas postsynaptic G protein-coupled K(+)
      (Kir3/GIRK) currents were unaffected. The frequency, but not amplitude, of
      miniature inhibitory postsynaptic currents was increased in beta-arrestin2
      knockout mice, indicating a higher release probability compared to WT mice. The
      increased release probability resulted from increased cAMP levels because of
      impaired phosphodiesterase 4 function and conferred an enhanced efficacy of
      morphine to inhibit GABA release. Thus, beta-arrestin2 attenuates presynaptic
      inhibition by opioids independent of mu-opioid receptor-driven recruitment, which
      may make beta-arrestin2 a promising target for regulating analgesia.

PMID- 15718285
TI  - Acetaldehyde disrupts tight junctions and adherens junctions in human colonic
      mucosa: protection by EGF and L-glutamine.
AB  - Acetaldehyde, a toxic metabolite of ethanol oxidation, is suggested to play a
      role in the increased risk for gastrointestinal cancers in alcoholics. In the
      present study, the effect of acetaldehyde on tyrosine phosphorylation,
      immunofluorescence localization, and detergent-insoluble fractions of the tight
      junction and the adherens junction proteins was determined in the human colonic
      mucosa. The role of EGF and L-glutamine in prevention of acetaldehyde-induced
      effects was also evaluated. Acetaldehyde reduced the protein tyrosine phosphatase
      activity, thereby increasing the tyrosine phosphorylation of occludin, E
      cadherin, and beta-catenin. The levels of occludin, zonula occludens-1, E
      cadherin, and beta-catenin in detergent-insoluble fractions were reduced by
      acetaldehyde, while it increased their levels in detergent-soluble fractions.
      Pretreatment with EGF or L-glutamine prevented acetaldehyde-induced protein
      tyrosine phosphorylation, redistribution from intercellular junctions, and
      reduction in the levels of detergent-insoluble fractions of occludin, zonula
      occludens-1, E-cadherin, and beta-catenin. These results demonstrate that
      acetaldehyde induces tyrosine phosphorylation and disrupts tight junction and
      adherens junction in human colonic mucosa, which can be prevented by EGF and
      glutamine.

PMID- 15718286
TI  - Which GP deals better with depressed patients in primary care in Kastamonu,
      Turkey: the impacts of 'interest in psychiatry' and 'continuous medical
      education'.

PMID- 15718287
TI  - Delivery of beta-galactosidase to mouse brain via the blood-brain barrier
      transferrin receptor.
AB  - Enzyme replacement therapy of lysosomal storage disorders is complicated by the
      lack of enzyme transport across the blood-brain barrier (BBB). The present
      studies evaluate the delivery of a model enzyme across the BBB following enzyme
      conjugation to a BBB receptor-specific monoclonal antibody (mAb). Bacterial beta
      galactosidase (116 kDa) was conjugated to the rat 8D3 mAb to the rat transferrin
      receptor (TfR) via a streptavidin-biotin linkage. The unconjugated beta
      galactosidase or the beta-galactosidase-8D3 conjugate was injected intravenously
      in adult mice, and enzyme activity was measured at 1 and 4 h in brain and
      peripheral organs (liver, spleen, kidney, and heart). Unconjugated beta
      galactosidase was rapidly removed from the blood compartment owing to avid uptake
      by liver and spleen. There was minimal uptake of the unconjugated beta
      galactosidase by brain. Following conjugation of the enzyme to the 8D3 TfRmAb,
      there was a 10-fold increase in brain uptake of the enzyme based on measurement
      of enzyme activity. Histochemistry of brain showed localization of the enzyme in
      the intraendothelial compartment of brain following intravenous injection of the
      enzyme-mAb conjugate. The capillary depletion technique showed that more than 90%
      of the enzyme-8D3 conjugate that entered into the endothelial compartment of
      brain passed through the BBB to enter brain parenchyma. In conclusion, high
      molecular weight enzymes, such as bacterial beta-galactosidase, can be conjugated
      to BBB targeting antibodies for effective delivery across the BBB in vivo. Fusion
      proteins comprised of BBB targeting antibodies and recombinant enzymes could be
      therapeutic in the treatment of the brain in human lysosomal storage disorders.

PMID- 15718288
TI  - Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine
      coadministration during exercise testing in healthy premenopausal women.
AB  - Premenopausal women may be most vulnerable to acute coronary syndromes at a point
      in their menstrual cycle when their plasma estrogen levels are the lowest during
      and immediately after menstruation. Metoprolol is a first-line drug in the
      management of patients with acute coronary syndrome; however, when metoprolol was
      marketed in 1982, women were largely excluded from clinical trials. Furthermore,
      the over-the-counter antihistamine diphenhydramine inhibited the metabolism of
      the CYP2D6 substrate metoprolol in healthy, young men with pharmacokinetic and
      pharmacodynamic consequences. The pharmacokinetics and pharmacodynamics of
      metoprolol and its interaction with diphenhydramine were investigated in a
      randomized, double-blind, crossover, placebo-controlled manner in healthy,
      premenopausal extensive (EM; n = 16) and poor metabolizer (PM; n = 4) women
      immediately after menstruation. During the placebo phase, EMs had between 5.2-
      and 8.4-fold higher total clearance (CL/F) of R- and S-metoprolol compared with
      PMs, whereas the latter had a 35% greater area under the effect curve (AUEC) and
      60% greater EC(50) value for heart rate reduction than EMs (all P < 0.05).
      Diphenhydramine coadmininstration caused a 2.2- to 3.2-fold decrease in CL/F of
      metoprolol enantiomers with a resulting 21% increase in AUEC and 29% increase in
      EC(50) value for heart rate reduction in EMs (all P < 0.05). This is the first
      study to report an in-depth elucidation of metoprolol's pharmacokinetics and
      hemodynamics in premenopausal EM and PM women at a point in their menstrual cycle
      when vulnerability for acute coronary events may be greatest. Caution is
      warranted when the over-the-counter antihistamine diphenhydramine is part of a
      chronic therapeutic regimen.

PMID- 15718289
TI  - Cyclooxygenase-2 is an obligatory factor in methamphetamine-induced
      neurotoxicity.
AB  - Methamphetamine causes persistent damage to dopamine nerve endings of the
      striatum. The mechanisms underlying its neurotoxicity are not fully understood,
      but considerable evidence points to oxidative stress as a probable mechanism. A
      recent microarray analysis of gene expression changes caused by methamphetamine
      revealed that cyclooxygenase-2 (COX-2) was induced along with its transcription
      factor CCAAT/enhancer-binding protein (Thomas DM, Francescutti-Verbeem DM, Liu X,
      and Kuhn DM, 2004). We report presently that methamphetamine increases striatal
      expression of COX-2 protein. Cyclooxygenase-1 (COX-1) expression was not changed.
      Mice bearing a null mutation of the gene for COX-2 were resistant to
      methamphetamine-induced neurotoxicity. COX-1 knockouts, like wild-type mice,
      showed extensive dopamine nerve terminal damage. Selective inhibitors of COX-1 [5
      (4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole (SC-560)], COX-2
      [N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulfonamide (NS-398), rofecoxib], or
      COX-3 (antipyrine) or a nonselective inhibitor of the COX-1/2 isoforms
      (ketoprofen) did not protect mice from neurotoxicity. Finally, methamphetamine
      did not change striatal prostaglandin E(2) content. Taken together, these data
      suggest that COX-2 is an obligatory factor in methamphetamine-induced
      neurotoxicity. The functional aspect of COX-2 that contributes to drug-induced
      neurotoxicity does not appear to be its prostaglandin synthetic capacity.
      Instead, the peroxidase activity associated with COX-2, which can lead to the
      formation of reactive oxygen species and dopamine quinones, can account for its
      role.

PMID- 15718290
TI  - The human chorionic gonadotropin-beta arginine68 to glutamic acid substitution
      fixes the conformation of the C-terminal peptide.
AB  - Wild-type human chorionic gonadotropin (hCG) has been used as a contraceptive
      vaccine. However, extensive sequence homology with LH elicits production of cross
      reactive antibodies. Substitution of arginine(68) of the beta-subunit (hCG(beta))
      with glutamic acid (R68E) profoundly reduces the cross-reactivity while
      refocusing the immune response to the hCG(beta)-specific C-terminal peptide
      (CTP). To investigate the molecular basis for this change in epitope usage, we
      immunized mice with a plasmid encoding a truncated hCG(beta)-R68E chain lacking
      the CTP. The animals produced LH-cross-reactive antibodies, suggesting that the
      refocused immunogenicity of R68E is a consequence of epitope masking by a novel
      disposition of the CTP in the mutant rather than a structural change in the cross
      reactive epitope region. This explanation was strongly supported by surface
      plasmon resonance analysis using a panel of anti-hCG(beta)-specific and anti
      hCG(beta)/LH cross-reactive monoclonal antibodies (mAbs). Whereas the binding of
      the LH cross-reactive mAbs to hCG(beta)-R68E was eliminated, mAbs reacting with
      hCG(beta)-specific epitopes bound to hCG(beta) and hCG(beta)-R68E with identical
      affinities. In a separate series of experiments, we observed that LH cross
      reactive epitopes were silent after immunization with a plasmid encoding a
      membrane form of hCG(beta)-R68E, as previously observed with the soluble mutant
      protein itself. In contrast, the plasmid encoding the soluble secreted form of
      hCG(beta)-R68E evoked LH cross-reactive antibodies, albeit of relatively low
      titer, suggesting that the handling and processing of the proteins produced by
      the two constructs differed.

PMID- 15718291
TI  - Follicle-stimulating hormone induction of ovarian insulin-like growth factor
      binding protein-3 transcription requires a TATA box-binding protein and the
      protein kinase A and phosphatidylinositol-3 kinase pathways.
AB  - The current study was done to elucidate the mechanism of the FSH stimulation of
      IGF-binding protein 3 (IGFBP-3) expression and map the FSH response element on
      the pig IGFBP-3 promoter. Forskolin induced IGFBP-3 reporter activity in
      transiently transfected granulosa cells. The protein kinase A (PKA) inhibitor [N
      [2-(p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, 2HCl] (and
      cotransfection with a PKA inhibitor expression vector), the phosphatidylinositol
      3 kinase inhibitor [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], and the
      ERK inhibitor [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene], all
      blocked FSH stimulation. Use of serial deletion constructs and site-directed
      mutagenesis show that a TATA box-binding protein site is required for FSH
      stimulation and that a specific protein 1 (Sp1) site is required for basal
      transcription. Gel shift assays of nuclear protein with a -61/-25 probe detected
      four protein-DNA complexes, with bands I and II having significantly higher
      intensities in FSH-treated cells than in controls. Mutation of the Sp1 site
      prevented formation of bands I and II whereas mutation of the TATA box-binding
      protein site prevented formation of band IV. Use of specific antibodies showed
      that Sp1 participates in formation of band I, Sp3 band II, and p300 in both I and
      II. Band III was nonspecifically competed out. We conclude that FSH stimulation
      of IGFBP-3 transcription is mediated by cAMP via the PKA pathway and requires the
      P1-3 kinase and likely the MAPK pathways.

PMID- 15718292
TI  - Evolution of the pregnane x receptor: adaptation to cross-species differences in
      biliary bile salts.
AB  - The pregnane X receptor (PXR) regulates the metabolism and elimination of bile
      salts, steroids, and xenobiotics. The sequence of the PXR ligand-binding domain
      diverges extensively between different animals, suggesting interspecies
      differences in ligands. Of the endogenous ligands known to activate PXR, biliary
      bile salts vary the most across vertebrate species, ranging from 27-carbon (C27)
      bile alcohol sulfates (early fish, amphibians) to C24 bile acids (birds,
      mammals). Using a luciferase-based reporter assay, human PXR was activated by a
      wide variety of bile salts. In contrast, zebrafish PXR was activated efficiently
      only by cyprinol sulfate, the major zebrafish bile salt, but not by recent bile
      acids. Chicken, mouse, rat, and rabbit PXRs were all activated by species
      specific bile acids and by early fish bile alcohol sulfates. In addition,
      phylogenetic analysis using maximum likelihood demonstrated evidence for
      nonneutral evolution of the PXR ligand-binding domain. PXR activation by bile
      salts has expanded from narrow specificity for C27 bile alcohol sulfates (early
      fish) to a broader specificity for recent bile acids (birds, mammals). PXR
      specificity for bile salts has thus paralleled the increasing complexity of the
      bile salt synthetic pathway during vertebrate evolution, an unusual example of
      ligand-receptor coevolution in the nuclear hormone receptor superfamily.

PMID- 15718293
TI  - Thyroid transcription factor 1 rescues PAX8/p300 synergism impaired by a natural
      PAX8 paired domain mutation with dominant negative activity.
AB  - Mutations in the paired domain transcription factor PAX8 are a rare cause of
      congenital hypothyroidism due to thyroid dysgenesis. We identified a novel and
      unique PAX8 mutation segregating in seven affected members of a three-generations
      family. The mutation replaces an invariant serine residue within helix 2 of the
      paired DNA-binding domain for phenylalanine. The mutant protein (PAX8-S48F) does
      not induce the thyroglobulin promoter in nonthyroid cells, but displays almost
      half of wild-type PAX8 activity in thyroid cells. PAX8-S48F shows no defect in
      expression, nuclear targeting, or DNA binding and retains the ability to
      synergize with thyroid transcription factor 1 (TTF-1, NKX2.1). However, we found
      that in nonthyroid cells, the acetylation-independent synergism with the general
      transcriptional adaptor p300 is completely abrogated, suggesting that PAX8-S48F
      may be unable to efficiently recruit p300. Reconstitution experiments in
      nonthyroid cells reveal that TTF-1 can partially rescue PAX8-S48F/p300 synergism
      and thus reproduce the situation in thyroid cells. These functional
      characteristics result in a dominant negative effect of PAX8-S48F on coexpressed
      wild-type PAX8 activity, which is not observed in paired domain mutations with
      DNA binding defect. Our results describe the first dominant negative missense
      mutation in a paired domain and provide evidence for a crucial role of the p300
      coactivator in mediating the functional synergism between PAX8 and TTF-1 in
      thyroid-specific gene expression.

PMID- 15718294
TI  - Identification of antisense nucleic acid hybridization sites in mRNA molecules
      with self-quenching fluorescent reporter molecules.
AB  - We describe a physical mRNA mapping strategy employing fluorescent self-quenching
      reporter molecules (SQRMs) that facilitates the identification of mRNA sequence
      accessible for hybridization with antisense nucleic acids in vitro and in vivo,
      real time. SQRMs are 20-30 base oligodeoxynucleotides with 5-6 bp complementary
      ends to which a 5' fluorophore and 3' quenching group are attached. Alone, the
      SQRM complementary ends form a stem that holds the fluorophore and quencher in
      contact. When the SQRM forms base pairs with its target, the structure separates
      the fluorophore from the quencher. This event can be reported by fluorescence
      emission when the fluorophore is excited. The stem-loop of the SQRM suggests that
      SQRM be made to target natural stem-loop structures formed during mRNA synthesis.
      The general utility of this method is demonstrated by SQRM identification of
      targetable sequence within c-myb and bcl-6 mRNA. Corresponding antisense
      oligonucleotides reduce these gene products in cells.

PMID- 15718295
TI  - Effective transcriptome amplification for expression profiling on sense-oriented
      oligonucleotide microarrays.
AB  - Gene expression analysis using microarrays of synthetic long oligonucleotides is
      limited in that it requires substantial amounts of RNA. To obtain these
      quantities from minute amounts of starting material, protocols were developed
      that linearly amplify mRNA by cDNA synthesis and in vitro transcription. Since
      orientation of the product is antisense (aRNA), it is inapplicable for dye
      labelling by reverse transcription and hybridization to sense-oriented
      oligonucleotide arrays. Here, we introduce a novel protocol in which aRNA
      labelling is achieved by a combination of two reverse and one forward
      transcription reactions followed by dye-incorporation using Klenow fragment,
      generating fluorescent antisense cDNA. We demonstrate high fidelity in arrays
      using up to 10(5)-fold amplification, starting from 2 ng total RNA. The generated
      data are highly reproducible and maintain relative gene expression levels between
      samples. These results demonstrate that our protocol describes an efficient and
      reliable technique to expand the applicability of oligonucleotide arrays to
      studies where RNA is the limited source material.

PMID- 15718296
TI  - Toxin-antitoxin loci are highly abundant in free-living but lost from host
      associated prokaryotes.
AB  - Prokaryotic chromosomes code for toxin-antitoxin (TA) loci, often in multiple
      copies. In E.coli, experimental evidence indicates that TA loci are stress
      response elements that help cells survive unfavorable growth conditions. The
      first gene in a TA operon codes for an antitoxin that combines with and
      neutralizes a regulatory 'toxin', encoded by the second gene. RelE and MazF
      toxins are regulators of translation that cleave mRNA and function, in interplay
      with tmRNA, in quality control of gene expression. Here, we present the results
      from an exhaustive search for TA loci in 126 completely sequenced prokaryotic
      genomes (16 archaea and 110 bacteria). We identified 671 TA loci belonging to the
      seven known TA gene families. Surprisingly, obligate intracellular organisms were
      devoid of TA loci, whereas free-living slowly growing prokaryotes had
      particularly many (38 in Mycobacterium tuberculosis and 43 in Nitrosomonas
      europaea). In many cases, TA loci were clustered and closely linked to mobile
      genetic elements. In the most extreme of these cases, all 13 TA loci of Vibrio
      cholerae were bona fide integron elements located in the V.cholerae mega
      integron. These observations strongly suggest that TA loci are mobile cassettes
      that move frequently within and between chromosomes and also lend support to the
      hypothesis that TA loci function as stress-response elements beneficial to free
      living prokaryotes.

PMID- 15718297
TI  - HIV-1 integrase crosslinked oligomers are active in vitro.
AB  - The oligomeric state of active human immunodeficiency virus type 1 (HIV-1)
      integrase (IN) has not been clearly elucidated. We analyzed the activity of the
      different purified oligomeric forms of recombinant IN obtained after
      stabilization by platinum crosslinking. The crosslinked tetramer isolated by gel
      chromatography was able to catalyze the full-site integration of the two viral
      LTR ends into a target DNA in vitro, whereas the isolated dimeric form of the
      enzyme was involved in the processing and integration of only one viral end.
      Accurate concerted integration by IN tetramers was confirmed by cloning and
      sequencing. Kinetic studies of DNA-integrase complexes led us to propose a model
      explaining the formation of an active complex. Our data suggest that the
      tetrameric IN bound to the viral DNA ends is the minimal complex involved in the
      concerted integration of both LTRs and should be the oligomeric form targeted by
      future inhibitors.

PMID- 15718298
TI  - Direct transcriptional repression of the genes encoding the zinc-finger proteins
      Gfi1b and Gfi1 by Gfi1b.
AB  - Gfi1b is a 37 kDa transcriptional repressor with six zinc-finger domains that is
      differentially expressed during hemato- and lymphopoiesis. We show here that
      transcription from the Gfi1b gene locus is silenced in the spleen but not in the
      bone marrow of transgenic mice that constitutively express Gfi1b under the
      control of the pan-hematopoietic vav promoter. Sequence analysis of the Gfi1b
      promoter showed the presence of potential Gfi1/Gfi1b-binding sites close to the
      mRNA start site. The expression of reporter gene constructs containing the Gfi1b
      core promoter appended to the luciferase gene were strongly repressed in the
      presence of exogenous Gfi1b. Moreover, analysis of combinatorial mutant mice that
      carry the vav-Gfi1b transgene and a green fluorescent protein-tagged Gfi1 gene
      locus demonstrated that the Gfi1 gene can be repressed by Gfi1b. Direct binding
      of Gfi1b and Gfi1 to the potential binding sites in the Gfi1b promoter could be
      demonstrated by gel-shift analyses in vitro. Chromatin-immunoprecipitation
      experiments showed that both the Gfi1b and the Gfi1 promoter are indeed occupied
      by Gfi1b in vivo. Hence, we conclude from our data that Gfi1b can auto-repress
      its own expression, but, in addition, is also able to cross-repress expression of
      the Gfi1 gene most likely in a cell type specific manner.

PMID- 15718299
TI  - Characterization of the ATPase and unwinding activities of the yeast DEAD-box
      protein Has1p and the analysis of the roles of the conserved motifs.
AB  - The yeast DEAD-box protein Has1p is required for the maturation of 18S rRNA, the
      biogenesis of 40S r-subunits and for the processing of 27S pre-rRNAs during 60S r
      subunit biogenesis. We purified recombinant Has1p and characterized its
      biochemical activities. We show that Has1p is an RNA-dependent ATPase in vitro
      and that it is able to unwind RNA/DNA duplexes in an ATP-dependent manner. We
      also report a mutational analysis of the conserved residues in motif I
      (86AKTGSGKT93), motif III (228SAT230) and motif VI (375HRVGRTARG383). The in vivo
      lethal K92A substitution in motif I abolishes ATPase activity in vitro. The
      mutations S228A and T230A partially dissociate ATPase and helicase activities,
      and they have cold-sensitive and lethal growth phenotypes, respectively. The
      H375E substitution in motif VI significantly decreased helicase but not ATPase
      activity and was lethal in vivo. These results suggest that both ATPase and
      unwinding activities are required in vivo. Has1p possesses a Walker A-like motif
      downstream of motif VI (383GTKGKGKS390). K389A substitution in this motif
      significantly increases the Has1p activity in vitro, which indicates it
      potentially plays a role as a negative regulator. Finally, rRNAs and poly(A) RNA
      serve as the best stimulators of the ATPase activity of Has1p among the tested
      RNAs.

PMID- 15718300
TI  - The relationship between the prothrombin upstream sequence element and the
      G20210A polymorphism: the influence of a competitive environment for mRNA 3'-end
      formation.
AB  - The human prothrombin G20210A polymorphism located at the 3' cleavage site of the
      mRNA results in elevated plasma prothrombin levels and increased risk of venous
      thrombosis. This polymorphism has been shown to directly influence a variety of
      processes related to prothrombin mRNA metabolism. We have constructed plasmids
      that express the full-length prothrombin mRNA that is polyadenylated at its
      natural site. The A allele prothrombin variant was more efficient than the G
      allele at promoting cleavage at this site in the presence of a competing poly (A)
      sequence. In the absence of competition, both allelic variants give rise to a
      similar level of cleavage site heterogeneity. An upstream sequence element (USE)
      was also identified within the prothrombin 3'-UTR. When placed upstream of two
      competing poly (A) sites, the USE directed cleavage preferentially to the
      proximal poly (A) site. In the absence of competition, the USE had no effect on
      cleavage site selection. This study suggests that the basis for the increase in
      prothrombin expression in A allele carriers is not due to allelic changes in
      cleavage site selection per se. In addition, the functionality of USEs needs to
      be considered within the context of endogenous sequence architecture.

PMID- 15718301
TI  - Mms22p protects Saccharomyces cerevisiae from DNA damage induced by topoisomerase
      II.
AB  - The cleavage reaction of topoisomerase II, which creates double-stranded DNA
      breaks, plays a central role in both the cure and initiation of cancer.
      Therefore, it is important to understand the cellular processes that repair
      topoisomerase II-generated DNA damage. Using a genome-wide approach with
      Saccharomyces cerevisiae, we found that Deltamre11, Deltaxrs2, Deltarad50,
      Deltarad51, Deltarad52, Deltarad54, Deltarad55, Deltarad57 and Deltamms22 strains
      were hypersensitive to etoposide, a drug that specifically increases levels of
      topoisomerase II-mediated DNA breaks. These results confirm that the single
      strand invasion pathway of homologous recombination is the major pathway that
      repairs topoisomerase II-induced DNA damage in yeast and also indicate an
      important role for Mms22p. Although Deltamms22 strains are sensitive to several
      DNA-damaging agents, little is known about the function of Mms22p. Deltamms22
      cultures accumulate in G2/M, and display an abnormal cell cycle response to
      topoisomerase II-mediated DNA damage. MMS22 appears to function outside of the
      single-strand invasion pathway, but levels of etoposide-induced homologous
      recombination in Deltamms22 cells are lower than wild-type. MMS22 is epistatic
      with RTT101 and RTT107, genes that encode its protein binding partners. Finally,
      consistent with a role in DNA processes, Mms22p localizes to discrete nuclear
      foci, even in the absence of etoposide or its binding partners.

PMID- 15718303
TI  - Detection of 5'- and 3'-UTR-derived small RNAs and cis-encoded antisense RNAs in
      Escherichia coli.
AB  - Evidence is accumulating that small, noncoding RNAs are important regulatory
      molecules. Computational and experimental searches have led to the identification
      of approximately 60 small RNA genes in Escherichia coli. However, most of these
      studies focused on the intergenic regions and assumed that small RNAs were >50
      nt. Thus, the previous screens missed small RNAs encoded on the antisense strand
      of protein-coding genes and small RNAs of <50 nt. To identify additional small
      RNAs, we carried out a cloning-based screen focused on RNAs of 30-65 nt. In this
      screen, we identified RNA species corresponding to fragments of rRNAs, tRNAs and
      known small RNAs. Several of the small RNAs also corresponded to 5'- and 3'
      untranslated regions (UTRs) and internal fragments of mRNAs. Four of the 3'-UTR
      derived RNAs were highly abundant and two showed expression patterns that
      differed from the corresponding mRNAs, suggesting independent functions for the
      3'-UTR-derived small RNAs. We also detected three previously unidentified RNAs
      encoded in intergenic regions and RNAs from the long direct repeat and hok/sok
      elements. In addition, we identified a few small RNAs that are expressed opposite
      protein-coding genes and could base pair with 5' or 3' ends of the mRNAs with
      perfect complementarity.

PMID- 15718302
TI  - 8-vinyl-deoxyadenosine, an alternative fluorescent nucleoside analog to 2'
      deoxyribosyl-2-aminopurine with improved properties.
AB  - We report here the synthesis and the spectroscopic characterization of 8-vinyl
      deoxyadenosine (8vdA), a new fluorescent analog of deoxyadenosine. 8vdA was found
      to absorb and emit in the same wavelength range as 2'-deoxyribosyl-2-aminopurine
      (2AP), the most frequently used fluorescent nucleoside analog. Though the quantum
      yield of 8vdA is similar to that of 2AP, its molar absorption coefficient is
      about twice, enabling a more sensitive detection. Moreover, the fluorescence of
      8vdA was found to be sensitive to temperature and solvent but not to pH (around
      neutrality) or coupling to phosphate groups. Though 8vdA is base sensitive and
      susceptible to depurination, the corresponding phosphoramidite was successfully
      prepared and incorporated in oligonucleotides of the type d(CGT TTT XNX TTT TGC)
      where N = 8vdA and X = A, T or C. The 8vdA-labeled oligonucleotides gave more
      stable duplexes than the corresponding 2AP-labeled sequences when X = A or T,
      indicating that 8vdA is less perturbing than 2AP and probably adopts an anti
      conformation to preserve the Watson-Crick H-bonding. In addition, the quantum
      yield of 8vdA is significantly higher than 2AP in all tested oligonucleotides in
      both their single strand and duplex states. The steady-state and time-resolved
      fluorescence parameters of 8vdA and 2AP were found to depend similarly on the
      nature of their flanking residues and on base pairing, suggesting that their
      photophysics are governed by similar mechanisms. Taken together, our data suggest
      that 8vdA is a non perturbing nucleoside analog that may be used with improved
      sensitivity for the same applications as 2AP.

PMID- 15718304
TI  - Relative predicted protein levels of functionally associated proteins are
      conserved across organisms.
AB  - We show that the predicted protein levels of functionally related proteins change
      in a coordinated fashion over many unicellular organisms. For each protein, we
      created a profile containing a protein abundance measure in each of a set of
      organisms. We show that for functionally related proteins these profiles tend to
      be correlated. Using the Codon Adaptation Index as a predictor of protein
      abundance in 48 unicellular organisms, we demonstrated this phenomenon for two
      types of functional relations: for proteins that physically interact and for
      proteins involved in consecutive steps within a metabolic pathway. Our results
      suggest that the protein abundance levels of functionally related proteins co
      evolve.

PMID- 15718305
TI  - Prospective evaluation of the pharmacokinetics and toxicity profile of docetaxel
      in the elderly.
AB  - PURPOSE: To prospectively study the pharmacokinetics and toxicity profile of
      docetaxel in elderly patients with cancer. PATIENTS AND METHODS: Docetaxel was
      administered at a dose 75 mg/m(2) once every 3 weeks to 25 elderly cancer
      patients aged >/= 65 years and 26 cancer patients aged younger than 65 years.
      Pharmacokinetic studies and toxicity assessments were performed during the first
      cycle of therapy. RESULTS: Of 51 patients treated, 20 aged >/= 65 years (median,
      71 years; range, 65 to 80 years) and 20 aged younger than 65 years (median, 53
      years; range, 26 to 64 years) were assessable for pharmacokinetic studies, and 39
      were assessable for toxicity. Patient characteristics were similar (P >/= .15)
      between the two cohorts. Mean docetaxel clearance was not altered in the elderly
      versus younger patients: 30.1 L/h (standard deviation [SD] 18.3 L/h) v 30.0 L/h
      (SD, 14.8 L/h; P = .98). The percentage of patients with grade 4 and febrile
      neutropenia was higher in the elderly (63% and 16%, respectively) versus younger
      (30% and 0%, respectively) cohort, although this observation did not reach a
      level of statistical significance (P = .056). From logistic regression analysis,
      the odds ratio for a patient aged 65 years was 1.98 for developing grade 4
      neutropenia compared with a patient aged 50 years (P = .091). CONCLUSION:
      Docetaxel plasma pharmacokinetics are unaltered in elderly patients. Patients
      aged >/= 65 years appear to be more sensitive to docetaxel-induced neutropenia.

PMID- 15718306
TI  - Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced
      cancer.
AB  - PURPOSE: We determined the maximum-tolerated dose (MTD) and the dose-limiting
      toxicities (DLT) of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when infused
      on days 1, 8, and 15 of a 28-day cycle in advanced solid tumor patients. We also
      characterized the pharmacokinetics of 17-AAG, its effect on chaperone and client
      proteins, and whether cytochrome P450 (CYP) 3A5 and NAD(P)H:quinone
      oxidoreductase 1 (NQO1) polymorphisms affected 17-AAG disposition or toxicity.
      PATIENTS AND METHODS: An accelerated titration design was used. Biomarkers were
      measured in peripheral-blood mononuclear cells (PBMCs) at baseline and on days 1
      and 15, and pharmacokinetic analysis was performed on day 1 of cycle 1. CYP3A5*3
      and NQO1*2 genotypes were determined and correlated with pharmacokinetics and
      toxicity. RESULTS: Twenty-one patients received 52 courses at 11 dose levels.
      DLTs at 431 mg/m(2) were grade 3 bilirubin (n = 1), AST (n = 1), anemia (n = 1),
      nausea (n = 1), vomiting (n = 1), and myalgias (n = 1). No tumor responses were
      seen. 17-AAG consistently increased heat shock protein (Hsp) 70 levels in PBMCs.
      At the MTD, the clearance and half-life (t(1/2)) of 17-AAG were 11.6 L/h/m(2) and
      4.15 hours, respectively; whereas the active metabolite 17-aminogeldanamycin had
      a t(1/2) of 7.63 hours. The CYP3A5*3 and NQO1*2 polymorphisms were not associated
      with 17-AAG toxicity. The CYP3A5*3 polymorphism was associated with higher 17-AAG
      clearance. CONCLUSION: The MTD of weekly 17-AAG is 308 mg/m(2). 17-AAG induced
      Hsp70 in PBMCs, indicating that Hsp90 has been affected. Further evaluation of 17
      AAG is ongoing using a twice-weekly regimen, and this schedule of 17-AAG is being
      tested in combination with chemotherapy.

PMID- 15718307
TI  - Analysis of concerted expression of angiogenic growth factors in acute myeloid
      leukemia: expression of angiopoietin-2 represents an independent prognostic
      factor for overall survival.
AB  - PURPOSE: Bone marrow neoangiogenesis plays an important pathogenetic and possible
      prognostic role in acute myeloid leukemia (AML). Members of the vascular
      endothelial growth factor (VEGF) and angiopoietin family represent the most
      specific inducers of angiogenesis secreted by AML blasts. We therefore correlated
      expression of angiogenic factors with clinical variables. PATIENTS AND METHODS:
      We investigated the expression of VEGF-A, VEGF-C, angiopoietin-1 (Ang1),
      angiopoietin-2 (Ang2), and the receptor Tie2 by quantitative polymerase chain
      reaction in a cohort of 90 patients younger than 61 years with de novo AML
      entered into the German AML Suddeutsche Hamoblastose Gruppe Hannover 95 trial.
      Uni- and multivariate analyses were performed using clinical and gene expression
      variables. RESULTS: Univariate analysis of overall survival indicated the
      following variables as prognostic factors: good response on a day-15 bone marrow
      examination after initiation of induction chemotherapy, karyotype, and high Ang2
      expression. In multivariate analysis, only bad response and log Ang2 expression
      remained of statistical significance, with a hazard ratio of 3.51 (95% CI, 1.91
      to 6.47) and 0.75 (95% CI, 0.61 to 0.91), respectively. Subgroup analysis
      suggested that the prognostic impact of Ang2 expression was especially evident in
      cohorts with low VEGF-C and Ang1 mRNA levels. CONCLUSION: These results show that
      expression of Ang2 represents an independent prognostic factor in AML. Additional
      research into interactions of angiogenic cytokines in the pathogenesis of bone
      marrow angiogenesis in AML is warranted.

PMID- 15718308
TI  - Hyperfractionated accelerated chemoradiation with concurrent fluorouracil
      mitomycin is more effective than dose-escalated hyperfractionated accelerated
      radiation therapy alone in locally advanced head and neck cancer: final results
      of the radiotherapy cooperative clinical trials group of the German Cancer
      Society 95-06 Prospective Randomized Trial.
AB  - PURPOSE: To report the results and corresponding acute and late reactions of a
      prospective, randomized, clinical study in locally advanced head and neck cancer
      comparing concurrent fluorouracil (FU) and mitomycin (MMC) chemotherapy and
      hyperfractionated accelerated radiation therapy (C-HART; 70.6 Gy) to
      hyperfractionated accelerated radiation therapy alone (HART; 77.6 Gy). PATIENTS
      AND METHODS: Three hundred eighty-four stage III (6%) and IV (94%) oropharyngeal
      (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer patients were
      randomly assigned to receive either 30 Gy (2 Gy every day) followed by 1.4 Gy bid
      to a total of 70.6 Gy concurrently with FU (600 mg/m(2), 120 hours continuous
      infusion) days 1 through 5 and MMC (10 mg/m(2)) on days 5 and 36 (C-HART) or 14
      Gy (2 Gy every day) followed by 1.4 Gy bid to a total dose of 77.6 Gy (HART). The
      data were analyzed on an intent-to-treat basis. RESULTS: At 5 years, the
      locoregional control and overall survival rates were 49.9% and 28.6% for C-HART
      versus 37.4% and 23.7% for HART, respectively (P = .001 and P = .023,
      respectively). Progression-free and freedom from metastases rates were 29.3% and
      51.9% for C-HART versus 26.6% and 54.7% for HART, respectively (P = .009 and P =
      .575, respectively). For C-HART, maximum acute reactions of mucositis, moist
      desquamation, and erythema were lower than with HART, whereas no differences in
      late reactions and overall rates of secondary neoplasms were observed.
      CONCLUSION: C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with
      comparable or less acute reactions and equivalent late reactions, indicating an
      improvement of the therapeutic ratio.

PMID- 15718309
TI  - [18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome
      of non-small-cell lung cancer.
AB  - PURPOSE: To determine whether the standardized uptake value (SUV) of
      [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a
      prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:
      One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall
      survival (OS), disease-free survival (DFS), distant metastasis-free survival
      (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier
      method and evaluated with the log-rank test. The prognostic significance was
      assessed by univariate and multivariate analyses. RESULTS: There were 93 patients
      treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for
      the SUV for the primary tumor showed the best discriminative value. The SUV for
      the primary tumor was a significant predictor of OS (P = .02) in both groups. Low
      SUVs (</= 5.0) showed significantly better DFS rates than those with high SUVs (>
      5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs (</= 5.0)
      indicated a significantly better DFS than those with high SUVs (> 5.0; stage I or
      II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point
      of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P
      = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that
      the SUV for the primary tumor was a significant prognostic factor for OS (P =
      .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the
      strongest prognostic factor among the patients treated by curative surgery or
      radiotherapy.

PMID- 15718310
TI  - Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin and
      paclitaxel in patients with stage III non-small-cell lung cancer: long-term
      results of a phase II study.
AB  - PURPOSE: To investigate the feasibility and activity of hyperfractionated
      radiation therapy (Hfx RT) and concurrent chemotherapy (CT) consisting of low
      dose, daily carboplatin and paclitaxel in patients with stage III non-small-cell
      lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-four patients started their
      treatment on day 1 with 30 mg/m(2) of paclitaxel administered by 1-hour infusion.
      Hfx RT began on day 2 using 1.3 Gy bid to a total dose of 67.6 Gy and concurrent
      low-dose daily CT consisting of 25 mg/m(2) of carboplatin and 10 mg/m(2) of
      paclitaxel, both given Mondays to Fridays during RT course. RESULTS: Objective
      response rate was 83% and included complete response in 27 patients (42%) and
      partial response in 26 patients (41%). Ten patients (16%) had stable disease,
      whereas only one patient (2%) had progressive disease. The median survival time
      was 28 months, and 3- and 5-year survival rates were 37% and 26%, respectively.
      The median time to local progression was 26 months, and 3- and 5-year local
      progression-free survival rates were 37% and 33%, respectively. The median time
      to distant metastasis was 25 months, and 3- and 5- year distant metastasis-free
      survival rates were 37% and 31%, respectively. Acute high-grade (>/= grade 3)
      toxicity was hematologic (25%), esophageal (17%), bronchopulmonary (13%), and
      skin (9%). Late high-grade toxicity was infrequent. CONCLUSION: This combined Hfx
      RT/TC regimen produced results that are among the best ever reported and warrants
      further study in a prospective randomized fashion.

PMID- 15718311
TI  - Relationship of epidermal growth factor receptor expression to ErbB-2 signaling
      activity and prognosis in breast cancer patients.
AB  - PURPOSE: To examine the relationship of epidermal growth factor receptor (EGFR)
      expression to ErbB-2 signaling activity in breast cancer and the impact that this
      interaction has on the prognosis of patients with early-stage breast cancer.
      PATIENTS AND METHODS: Paraffin tumor sections were collected retrospectively from
      807 breast cancer patients diagnosed between 1976 and 1983. Immunohistochemical
      assays for ErbB-2, phosphorylated (activated) ErbB-2, and EGFR were performed,
      and the results were correlated with clinicopathologic variables and outcome.
      RESULTS: EGFR expression was detectable in 15% of 807 invasive breast cancers,
      including 35% of the 306 ErbB-2-positive patients. Conversely, the majority (87%)
      of EGFR-positive tumors co-overexpressed ErbB-2. Ninety-seven percent of tumors
      with phosphorylated ErbB-2 co-overexpressed EGFR. Patients whose cancers
      demonstrated ErbB-2 phosphorylation or co-overexpression of ErbB-2 and EGFR had
      the shortest survival. In contrast, patients whose tumors were negative for all
      three markers and those tumors that expressed only EGFR or only nonphosphorylated
      ErbB-2 had a relatively favorable outcome. CONCLUSION: These data provide the
      first clinical evidence that EGFR expression is linked to activation of ErbB-2 in
      human breast cancers. We have further shown that the adverse prognostic value of
      ErbB-2 overexpression is observed only when ErbB-2 is in the phosphorylated
      (activated) state or coexpressed with EGFR. These data suggest that ligand
      dependent mechanisms of ErbB-2 activation are important in human breast cancer.
      These results also suggest that agents targeting EGFR may be useful in the
      treatment of tumors with activated ErbB-2.

PMID- 15718312
TI  - Clinical role of multidrug resistance protein 1 expression in chemotherapy
      resistance in early-stage breast cancer: the Austrian Breast and Colorectal
      Cancer Study Group.
AB  - PURPOSE: The multidrug resistance protein 1 (MRP1) is expressed in human breast
      cancer cells and may contribute to the clinical drug resistance of breast cancer
      patients. Therefore, we determined the impact of MRP1 expression on the clinical
      outcome of adjuvant therapy in patients with early-stage breast cancer. PATIENTS
      AND METHODS: Immunostaining for MRP1 was performed on tissue sections from 516
      premenopausal, hormone receptor-positive breast cancer patients with stage I and
      II disease. Statistical analyses were performed to assess the effect of MRP1
      expression on survival and to test for interaction between MRP1 expression and
      treatment. RESULTS: MRP1 expression independently predicted shorter relapse-free
      survival (RFS) and overall survival (OS) in patients treated with
      cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] =
      1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P =
      .02), but it did not predict shorter RFS and OS in patients who received
      tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR =
      0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1
      expression and treatment were statistically significant for both RFS (P = .04)
      and OS (P = .006). CONCLUSION: Our data suggest that MRP1 expression plays an
      important role in the clinical resistance to adjuvant CMF chemotherapy but does
      not seem to affect response to adjuvant endocrine treatment with tamoxifen plus
      goserelin. Thus, MRP1 may be a useful marker for the selection of patients with
      early-stage breast cancer for the appropriate adjuvant therapy after prospective
      confirmatory evaluation.

PMID- 15718313
TI  - Patterns of resistance and incomplete response to docetaxel by gene expression
      profiling in breast cancer patients.
AB  - PURPOSE: Chemotherapy for operable breast cancer decreases the risk of death.
      Docetaxel is one of the most active agents in breast cancer, but resistance or
      incomplete response is frequent. PATIENTS AND METHODS: Core biopsies from 24
      patients were obtained before treatment with neoadjuvant docetaxel (four cycles,
      100 mg/m(2) every 3 weeks), and response was assessed after chemotherapy. After 3
      months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained,
      and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor
      cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6
      microg) was extracted for cDNA array analysis using the Affymetrix HgU95-Av2
      GeneChip (Affymetrix, Santa Clara, CA). RESULTS: From the initial core biopsies,
      differential patterns of expression of 92 genes correlated with docetaxel
      response (P = .001). However, the molecular patterns of the residual cancers
      after 3 months of docetaxel treatment were strikingly similar, independent of
      initial sensitivity or resistance. This relative genetic homogeneity after
      treatment was observed in both LCM and non-LCM surgical specimens. The residual
      tumor after treatment in tumors that were initially sensitive indicates selection
      of a residual and resistant subpopulation of cells. The gene expression pattern
      was populated by genes involved in cell cycle arrest at G(2)M (eg, mitotic
      cyclins and cdc2) and survival pathways involving the mammalian target of
      rapamycin. CONCLUSION: A specific and consistent gene expression pattern was
      found in residual tumors after docetaxel treatment. These profiles provide
      therapeutic targets that could lead to improved treatment.

PMID- 15718314
TI  - First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in
      patients with breast cancer: a multicenter, double-blind, placebo-controlled
      phase III study.
AB  - PURPOSE: We evaluated the efficacy of pegfilgrastim to reduce the incidence of
      febrile neutropenia associated with docetaxel in breast cancer patients. PATIENTS
      AND METHODS: Patients were randomly assigned to either placebo or pegfilgrastim 6
      mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2)
      docetaxel. The primary end point was the percentage of patients developing
      febrile neutropenia (defined as body temperature >/= 38.2 degrees C and
      neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after).
      Secondary end points were incidence of hospitalizations associated with a
      diagnosis of febrile neutropenia, intravenous (IV) anti-infectives required for
      febrile neutropenia, and the ability to maintain planned chemotherapy dose on
      time. Patients with febrile neutropenia were converted to open-label
      pegfilgrastim in subsequent cycles. RESULTS: Nine hundred twenty-eight patients
      received placebo (n = 465) or pegfilgrastim (n = 463). Patients receiving
      pegfilgrastim, compared with patients receiving placebo, had a lower incidence of
      febrile neutropenia (1% v 17%, respectively; P < .001), febrile neutropenia
      related hospitalization (1% v 14%, respectively; P < .001), and use of IV anti
      infectives (2% v 10%, respectively; P < .001). The percentage of patients
      receiving the planned dose on time was similar between patients receiving
      pegfilgrastim and patients who initially received placebo (80% and 78%,
      respectively), as would be expected of the study design. Pegfilgrastim was
      generally well tolerated and safe, and the adverse events reported were typical
      of this patient population. CONCLUSION: First and subsequent cycle use of
      pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly
      reduced febrile neutropenia, febrile neutropenia-related hospitalizations, and IV
      anti-infective use.

PMID- 15718315
TI  - Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the
      urothelium: a phase II Hoosier Oncology Group study.
AB  - PURPOSE: To evaluate the efficacy and toxicity of weekly paclitaxel and
      gemcitabine in patients with advanced transitional-cell carcinoma (TCC) of the
      urothelial tract. PATIENTS AND METHODS: Patients with advanced unresectable TCC
      were enrolled onto this multicenter, community-based, phase II trial. Initially,
      patients were treated with paclitaxel 110 mg/m(2) and gemcitabine 1,000 mg/m(2)
      by intravenous infusion on days 1, 8, and 15 every 28 days. Patients who had an
      objective response or stable disease continued treatment for a maximum of six
      courses. Paclitaxel was decreased to 90 mg/m(2) and gemcitabine was decreased to
      800 mg/m(2) for the last 12 patients because of a concerning incidence of
      pulmonary toxicity in the first 24 patients. RESULTS: Thirty-six patients were
      enrolled between September 1998 and March 2003. Twenty-four patients received the
      higher doses of paclitaxel and gemcitabine, and 12 patients received the lower
      doses. Twenty-five (69.4%) of 36 patients had major responses to treatment,
      including 15 patients (41.7%) with complete responses. With a median follow-up
      time of 38.7 months, the median survival time was 15.8 months. Grade 3 and 4
      toxicities included granulocytopenia (36.1%), thrombocytopenia (8.3%), and
      neuropathy (16.7%). Five patients (13.9%) had grades 3 to 5 pulmonary toxicity,
      and one patient had grade 2 pulmonary toxicity. CONCLUSION: Weekly paclitaxel and
      gemcitabine is an active regimen in the treatment of patients with advanced TCC.
      However, because of the high incidence of pulmonary toxicity associated with this
      schedule of paclitaxel and gemcitabine, we recommend against the use of this
      regimen in this patient population.

PMID- 15718316
TI  - Randomized trial comparing iridium implant plus external-beam radiation therapy
      with external-beam radiation therapy alone in node-negative locally advanced
      cancer of the prostate.
AB  - PURPOSE: To determine if iridium implant (IM) and external-beam radiation therapy
      (EBRT) is better than standard EBRT in locally advanced prostate cancer. METHODS:
      Patients with T2 and T3 prostate cancer with no evidence of metastatic disease
      were randomly assigned to EBRT of 66 Gy in 33 fractions during 6.5 weeks or to IM
      of 35 Gy delivered to the prostate during 48 hours plus EBRT of 40 Gy in 20
      fractions during 4 weeks. The primary outcome consisted of biochemical or
      clinical failure (BCF). BCF was defined by biochemical failure, clinical failure,
      or death as a result of prostate cancer. Secondary outcomes included 2-year
      postradiation biopsy positivity, toxicity, and survival. RESULTS: Between 1992
      and 1997, 51 patients were randomly assigned to receive IM plus EBRT, and 53
      patients were randomly assigned to receive EBRT alone. The median follow-up was
      8.2 years. In the IM plus EBRT arm, 17 patients (29%) experienced BCF compared
      with 33 patients (61%) in the EBRT arm (hazard ratio, 0.42; P = .0024). Eighty
      seven patients (84%) had a postradiation biopsy; 10 (24%) of 42 in the IM plus
      EBRT arm had biopsy positivity compared with 23 (51%) of 45 in the EBRT arm (odds
      ratio, 0.30; P = .015). Overall survival was 94% in the IM plus EBRT arm versus
      92% in the EBRT arm. CONCLUSION: The combination of IM plus EBRT was superior to
      EBRT alone for BCF and postradiation biopsy. This trial provides evidence that
      higher doses of radiation delivered in a shorter duration result in better local
      as well as biochemical control in locally advanced prostrate cancer.

PMID- 15718317
TI  - Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I
      Testicular Seminoma: a report on Medical Research Council Trial TE18, European
      Organisation for the Research and Treatment of Cancer Trial 30942
      (ISRCTN18525328).
AB  - PURPOSE: To assess the possibility of reducing radiotherapy doses without
      compromising efficacy in the management of patients with stage I seminoma.
      PATIENTS AND METHODS: Patients were randomly assigned 20 Gy/10 fractions over 2
      weeks or 30 Gy/15 fractions during 3 weeks after orchidectomy. They completed a
      symptom diary card during treatment and quality-of-life forms pre- and post
      treatment. The trial was powered to exclude absolute differences in 2-year
      relapse rates of 3% to 4% (alpha = .05 [one sided]; 90% power). RESULTS: From
      1995 to 1998, 625 patients were randomly assigned to treatment. Four weeks after
      starting radiotherapy, significantly more patients receiving 30 Gy reported
      moderate or severe lethargy (20% v 5%) and an inability to carry out their normal
      work (46% v 28%). However, by 12 weeks, levels in both groups were similar. With
      a median follow-up of 61 months, 10 and 11 relapses, respectively, have been
      reported in the 30- and 20-Gy groups (hazard ratio, 1.11; 90% CI, 0.54 to 2.28).
      The absolute difference in 2-year relapse rates is 0.7%; the lower 90% confidence
      limit is 2.9%. Only one patient has died from seminoma (allocated to the 20-Gy
      treatment group). CONCLUSION: Treatment with 20 Gy in 10 fractions is unlikely to
      produce relapse rates more than 3% higher than for standard 30 Gy radiation
      therapy, and data on an additional 469 patients randomly assigned in a subsequent
      trial support and strengthen these results. Reductions in morbidity enable
      patients to return to work more rapidly. Prolonged follow-up is required before
      any inference can be made about any impact of allocated treatment on new primary
      cancer diagnoses.

PMID- 15718318
TI  - Selective excision of metastatic brain tumors originating in the motor cortex
      with preservation of function.
AB  - PURPOSE: Brain metastases are common in patients with cancer and can cause
      considerable morbidity or death. Metastasis in eloquent areas of the brain,
      particularly the primary motor cortex, may present significant treatment
      challenges. PATIENTS AND METHODS: Seventeen consecutive patients with metastasis
      within the primary motor cortex underwent selective microsurgical tumor
      resection. Operative, hospital, neuroimaging, and follow-up information was
      reviewed. RESULTS: There were 10 women and seven men (mean age, 54.3 years) who
      underwent 17 operations for symptomatic brain metastases. Motor cortex was
      identified and tumor (mean volume, 10.2 cm(3)) was completely resected in all
      patients. Three patients had transient or reversible complications. Karnofsky
      performance scores improved in 16 of 17 patients at 4 weeks postoperatively, with
      a mean improvement of 1.8 grades compared with preoperative scores (P < .05).
      Overall survival of 16 patients with distant follow-up (> 6 months or until
      death) averaged 10.6 +/- 4.4 months, with nine of 16 (56%) assessable patients
      surviving 1 year or longer. Survival of these 16 patients, by recursive
      partitioning analysis (RPA), was 11.2, 13.3, and 6.7 months for RPA classes I,
      II, and III, respectively. The cause of death in 14 of 15 patients who have died
      was progressive systemic disease; in one patient it was a combination of systemic
      and distant CNS disease progression. There were no local CNS recurrences.
      CONCLUSION: Complete microsurgical resection of metastatic tumors in the primary
      motor cortex is feasible and efficacious, results in a sustained improvement in
      performance outcomes, and permits satisfactory long-term survival.

PMID- 15718319
TI  - Molecular staging in stage II and III melanoma patients and its effect on long
      term survival.
AB  - PURPOSE: To assess the prognostic value of serial reverse transcriptase
      polymerase chain reaction (RT-PCR) -based measurements of tyrosinase mRNA in
      peripheral blood of stage II and III melanoma patients. PATIENTS AND METHODS:
      During routine follow-up of American Joint Committee on Cancer stage II and III
      melanoma patients, serial testing for tyrosinase transcripts in peripheral blood
      was performed by RT-PCR. The PCR results were compared with the clinical data
      collected during the follow-up. RESULTS: Over a period of 3 years, 111 patients
      (78 stage II and 33 stage III patients) were enrolled, and tyrosinase
      determinations were carried out. The 6-year disease-specific survival probability
      was 97% for patients always showing negative RT-PCR results and 67% for patients
      who tested positive at least once. In a Cox proportional hazards model, the
      prognostic value of sex, age, site of primary tumor, histologic subtype, stage,
      Breslow's tumor thickness, Clark level, and the time-dependent variable PCR
      result was assessed. Patients with a positive RT-PCR test had a distinctly higher
      risk of dying from melanoma, with a hazard ratio of 12.6 (95% CI, 3.4 to 46.3; P
      < .001). CONCLUSION: Our study shows a strong association between PCR and disease
      specific survival time. Detection of tyrosinase mRNA in peripheral blood may be
      of similar importance for the clinical course of melanoma as the detection of
      micrometastatic disease in the sentinel lymph node. Whether a combination of
      these two factors leads to a better definition of the prognosis of melanoma
      patients is under investigation in current studies.

PMID- 15718320
TI  - Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced
      pancreatic cancer--a Groupe Tumeurs Digestives of the Federation Nationale des
      Centres de Lutte Contre le Cancer study.
AB  - PURPOSE: To evaluate response rate and toxicity of irinotecan and oxaliplatin
      plus fluorouracil (FU) and leucovorin (Folfirinox) in advanced pancreatic
      adenocarcinoma (APA). PATIENTS AND METHODS: Chemotherapy-naive patients with
      histologically proven APA and bidimensionally measurable disease were treated
      with Folfirinox therapy every 2 weeks, which comprised oxaliplatin 85 mg/m(2) and
      irinotecan 180 mg/m(2) plus leucovorin 400 mg/m(2) followed by bolus FU 400
      mg/m(2) on day 1, then FU 2,400 mg/m(2) as a 46-hour continuous infusion. Quality
      of life (QOL) was assessed using European Organisation for Research and Treatment
      of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). RESULTS: Forty-seven
      patients were entered, and 46 received treatment. Thirty-five patients (76%) had
      metastatic disease. A total of 356 cycles were delivered, with a median of eight
      cycles per patient (range, one to 24 cycles). All patients were assessable for
      safety. No toxic death occurred. Grade 3 to 4 neutropenia occurred in 52% of
      patients, including two patients with febrile neutropenia. Other relevant
      toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and diarrhea (17%)
      and grade 3 neuropathy (15%; Levi's scale). The confirmed response rate was 26%
      (95% CI, 13% to 39%), including 4% complete responses. Median time to progression
      was 8.2 months (95% CI, 5.3 to 11.6 months), and median overall survival was 10.2
      months (95% CI, 8.1 to 14.4 months). Between baseline and end of treatment,
      patients had improvement in all functional scales of the EORTC QLQ-C30, except
      cognitive functioning. Responders had major improvement in global QOL.
      CONCLUSION: With a good safety profile, a promising response rate, and an
      improvement in QOL, Folfirinox will be further assessed in a phase III trial.

PMID- 15718321
TI  - Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of
      pathologic response and not clinical parameters dictated patient outcome.
AB  - PURPOSE: Preoperative chemoradiotherapy may increase the R0 (curative) resection
      rate, overall survival (OS) duration, and disease-free survival (DFS) duration.
      We evaluated paclitaxel-based induction chemotherapy and chemoradiotherapy in
      patients with localized gastric or gastroesophageal adenocarcinoma to determine
      its feasibility, impact on the R0 resection rate, type of pathologic response,
      OS, and DFS. PATIENTS AND METHODS: Patients with operable, localized gastric, or
      gastroesophageal adenocarcinoma were eligible. Staging included endoscopic
      ultrasonography (EUS) and laparoscopy. Patients received two 28-day cycles of
      induction chemotherapy of fluorouracil, paclitaxel, and cisplatin followed by 45
      Gy of radiation and concurrent fluorouracil plus paclitaxel. The cancer was
      restaged and surgery was attempted. Postsurgery pathologic findings and R0
      resection were correlated with OS and DFS. RESULTS: Forty-one patients were
      enrolled. Most carcinomas were proximal (83%) and pretreatment stage EUST3 (85%).
      Forty patients (98%) underwent surgery, and 78% had an R0 resection. We observed
      a pathologic complete response (pathCR) rate of 20% and a pathologic partial
      response (pathPR) rate of 15% (< 10% residual cancer cells in the resected
      specimen). No pretreatment parameter (sex, cancer location, baseline T stage, or
      baseline N stage) predicted the type of postsurgery pathologic response, OS, or
      DFS. However, pathCR (P = .02), pathCR + pathPR (P = .006), R0 resection (P <
      .001), and postsurgery T and N stages (P = .01 and P < .001, respectively) were
      associated with OS. Same parameters were significantly correlated with DFS.
      Toxicity was manageable. CONCLUSION: The type of pathologic response but not
      pretreatment parameters was associated with OS and DFS. Efforts to increase the
      rate of pathologic response and better systemic cancer control are warranted.

PMID- 15718322
TI  - Predictive value of the pretreatment extent of disease system in hepatoblastoma:
      results from the International Society of Pediatric Oncology Liver Tumor Study
      Group SIOPEL-1 study.
AB  - PURPOSE: Preoperative staging (pretreatment extent of disease [PRETEXT]) was
      developed for the first prospective liver tumor study by the International
      Society of Pediatric Oncology (SIOPEL-1 study; preoperative chemotherapy and
      delayed surgery). Study aims were to analyze the accuracy and interobserver
      agreement of PRETEXT and to compare the predictive impact of three currently used
      staging systems. PATIENTS AND METHODS: Hepatoblastoma (HB) patients younger than
      16 years who underwent surgical resection (128 of 154 patients) were analyzed.
      The centrally reviewed preoperative staging was compared with postoperative
      pathology (accuracy) in 91 patients (81%), and the local center staging was
      compared with the central review (interobserver agreement) in 97 patients (86%),
      using the agreement beyond change method (weighted kappa). The predictive values
      of the three staging systems were compared in 110 patients (97%) using survival
      curves and Cox proportional hazard ratio estimates. RESULTS: Preoperative PRETEXT
      staging compared with pathology was correct in 51%, overstaged in 37%, and
      understaged in 12% of patients (weighted kappa = 0.44; 95% CI, 0.26 to 0.62). The
      weighted kappa value of the interobserver agreement was 0.76 (95% CI, 0.64 to
      0.88). The Children's Cancer Study Group/Pediatric Oncology Group-based staging
      system showed no predictive value for survival (P = .516), but the tumor-node
      metastasis-based system and PRETEXT system showed good predictive values (P =
      .0021 and P = .0006, respectively). PRETEXT seemed to be superior in the
      statistical fit. CONCLUSION: PRETEXT has moderate accuracy with a tendency to
      overstage patients, shows good interobserver agreement (reproducibility), shows
      superior predictive value for survival, offers the opportunity to monitor the
      effect of preoperative therapy, and can also be applied in patients who have not
      had operations. For comparability reasons, we recommend that all HB patients
      included in trials also be staged according to PRETEXT.

PMID- 15718323
TI  - Profile of patients with Kaposi's sarcoma in the era of highly active
      antiretroviral therapy.
AB  - PURPOSE: Since the advent of highly active antiretroviral therapy (HAART), the
      incidence of Kaposi's sarcoma (KS) among AIDS patients has declined both
      nationwide and in King County, Washington. We sought to compare clinical
      parameters of patients diagnosed with KS in the pre-HAART (1990 to 1996) and
      HAART (1997 to 2002) eras. METHODS: We used patient data abstracted from the
      Adult/Adolescent Spectrum of HIV-Related Diseases study of Public Health-Seattle
      and King County. RESULTS: Patients diagnosed with KS in the HAART era (n = 40)
      were significantly more likely (P < .05) than pre-HAART-era KS patients (n = 366)
      to be diagnosed with alcohol problems (43% v 18%), noninjection drug use (45% v
      18%), injection drug use (25% v 10%), psychosis (25% v 13%), and hypertension
      (13% v 2%). Although median CD4(+) count and HIV-1 viral load at the time of KS
      diagnosis were not significantly different between the two groups, significantly
      fewer (P < .01) HAART-era KS patients developed opportunistic illnesses (OIs)
      during their follow-up. The risk of dying among KS patients diagnosed in the
      HAART era is significantly lower (P < .01) than for KS patients diagnosed in the
      pre-HAART era (hazard ratio, 0.24). CONCLUSION: Although HAART-era KS patients in
      King County were as likely to have a depleted CD4(+) cell count and high HIV-1
      viral loads at the time of KS diagnosis as pre-HAART KS patients, they survived
      longer and fewer of them were diagnosed with other OIs. They also had an
      increased prevalence of substance abuse and mental illness, contributing to a
      dynamic and changing KS clinical profile.

PMID- 15718324
TI  - Does a history of childhood sexual abuse affect sexual outcomes in breast cancer
      survivors?
AB  - PURPOSE: Little is known about a history of childhood sexual abuse (CSA) in
      breast cancer survivors and its relationship to sexual functioning after cancer.
      As part of a larger survey study examining sexuality and intimacy in breast
      cancer survivors, we conducted in-person interviews with a subsample of
      participants. METHODS: A total of 147 women in Los Angeles, CA, and Washington,
      DC, completed a structured interview that addressed sexual socialization and a
      history of sexual abuse. Trained female interviewers conducted the interviews.
      Descriptive statistics and regression analyses were used to examine the
      prevalence of CSA, and its potential impact on sexual health and functioning.
      RESULTS: One in three women reported at least one CSA incident. Among women who
      had experienced CSA, 71% reported a single incident, and 22% reported a
      penetrative form of sexual contact. In multivariate regression analyses examining
      physical and psychological aspects of sexuality and body image, CSA was not a
      significant predictor of physical discomfort. However, a history of penetrative
      CSA was a significant predictor of psychological discomfort (P = .02).
      CONCLUSION: The prevalence of CSA in this sample was similar to the general
      population literature on this topic. In this small sample, a past history of CSA
      did not contribute significantly to the physical discomforts associated with
      sexual intimacy after breast cancer; however, our findings suggest that a past
      history of penetrative CSA is associated with increased psychological discomfort,
      and may warrant additional examination in future research.

PMID- 15718325
TI  - Psychoeducational intervention for patients with cutaneous malignant melanoma: a
      replication study.
AB  - PURPOSE: In 1993, a randomized intervention study among patients with malignant
      melanoma showed a significant decrease in psychological distress and increased
      coping capacity 6 months after the intervention and enhanced survival 6 years
      later. We applied a similar intervention with a few modifications in a randomized
      controlled trial among Danish patients with malignant melanoma and evaluated
      results on immediate and long-term effects on psychological distress and coping
      capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous
      malignant melanoma were randomly assigned to the control or intervention group.
      Patients in the intervention group were offered six weekly sessions of 2 hours of
      psychoeducation, consisting of health education, enhancement of problem-solving
      skills, stress management, and psychological support. The participants were
      assessed at baseline before random assignment and 6 and 12 months after surgery.
      The analyses of the main effects of the intervention were based on analyses of
      covariance. RESULTS: The patients in the intervention group showed significantly
      less fatigue, greater vigor, and lower total mood disturbance compared with the
      controls, and they used significantly more active-behavioral and active-cognitive
      coping than the patients in the control group. The improvements were only
      significant at first follow-up. CONCLUSION: The findings of this study support
      the results of an earlier intervention study among patients with malignant
      melanoma and indicate that a psychoeducational group intervention for such
      patients can decrease psychological distress and enhance effective coping.
      However, this effect is short term and the clinical relevance is not obvious.

PMID- 15718326
TI  - Communicating with realism and hope: incurable cancer patients' views on the
      disclosure of prognosis.
AB  - PURPOSE: To identify preferences for the process of prognostic discussion among
      patients with incurable metastatic cancer and variables associated with those
      preferences. PATIENTS AND METHODS: One hundred twenty-six (58%) of 218 patients
      invited onto the study participated. Eligible patients were the consecutive
      metastatic cancer patients of 30 oncologists, who were diagnosed within 6 weeks
      to 6 months before recruitment, over 18 years of age, and without known mental
      illness. Patients completed a postal survey measuring patient preferences for the
      manner of delivery of prognostic information, including how doctors might instill
      hope. RESULTS: Ninety-eight percent of patients wanted their doctor to be
      realistic, provide an opportunity to ask questions, and acknowledge them as an
      individual when discussing prognosis. Doctor behaviors rated the most hope giving
      included offering the most up to date treatment (90%), appearing to know all
      there is to know about the patient's cancer (87%), and saying that pain will be
      controlled (87%). The majority of patients indicated that the doctor appearing to
      be nervous or uncomfortable (91%), giving the prognosis to the family first
      (87%), or using euphemisms (82%) would not facilitate hope. Factor analysis
      revealed six general styles and three hope factors; the most strongly endorsed
      styles were realism and individualized care and the expert/positive/collaborative
      approach. A range of demographic, psychological, and disease factors were
      associated with preferred general and hope-giving styles, including anxiety,
      information-seeking behavior, expected survival, and age. CONCLUSION: The
      majority of patients preferred a realistic and individualized approach from the
      cancer specialist and detailed information when discussing prognosis.

PMID- 15718327
TI  - Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours
      after chemotherapy to prevent delayed emesis? Systematic re-evaluation of
      clinical evidence and drug cost implications.
AB  - PURPOSE: 5-Hydroxytryptamine-3 receptor antagonists (5-HT(3) antagonists) are
      effective for preventing acute chemotherapy-induced emesis but the benefits of
      continuing administration of these agents beyond 24 hours after chemotherapy
      (delayed emesis) remain unclear. The purpose of this study was to provide
      estimates of clinical efficacy and drug acquisition cost associated with
      administering 5-HT(3) antagonists beyond 24 hours, as monotherapy or as added to
      dexamethasone. METHODS: This analysis is based on the Cancer Care Ontario
      Practice Guidelines Initiative meta-analysis of the efficacy of 5-HT(3)
      antagonists. Results from the clinical trials covered in that meta-analysis were
      reanalyzed to provide estimates of absolute risk reductions (ARR) and numbers
      needed to treat (NNT) for 5-HT(3) antagonists, as monotherapy or as adjunct
      treatment. Numbers of 5-HT(3) antagonist unit doses per successfully treated
      patient were also calculated. RESULTS: Five studies (comprising 1,716 assessable
      patients) compared a 5-HT(3) antagonist with placebo; five studies (2,240
      patients) compared a combination of a 5-HT(3) antagonist and dexamethasone with
      dexamethasone monotherapy. ARR for monotherapy was only 8.2% (95% CI, 3.0% to
      13.4%). On average, 74 5-HT(3) antagonist doses must be administered to 12
      patients (NNT, 12.2; 95% CI, 7.5 to 33.4) not receiving dexamethasone to protect
      one patient from delayed emesis. In those patients receiving dexamethasone as
      standard antiemetic treatment in the delayed phase, the addition of a 5-HT(3)
      antagonist did not significantly improve control of delayed emesis as compared
      with dexamethasone monotherapy (ARR, 2.6%; 95% CI, -0.6% to 5.8%). CONCLUSION:
      Neither clinical evidence nor considerations of cost effectiveness justify using
      5-HT(3) antagonists beyond 24 hours after chemotherapy for prevention of delayed
      emesis.

PMID- 15718328
TI  - Combination of antiangiogenic therapy with other anticancer therapies: results,
      challenges, and open questions.
AB  - Angiogenesis is necessary for tumor growth. Drug discovery efforts have
      identified several potential therapeutic targets on endothelial cells and
      selective inhibitors capable of slowing tumor growth or producing tumor
      regression by blocking angiogenesis in in vivo tumor models. Certain
      antiangiogenic therapeutics increase the activity of cytotoxic anticancer
      treatments in preclinical models. More than 75 antiangiogenic compounds have
      entered clinical trials. Most of the early clinical testing was conducted in
      patients with advanced disease resistant to standard therapies. Several phase III
      trials have been undertaken to compare the efficacy of standard chemotherapy
      versus the same in combination with an experimental angiogenesis inhibitor.
      Preliminary results of the clinical studies suggest that single-agent
      antiangiogenic therapy is poorly active in advanced tumors. Although some of the
      results of combination trials are controversial, recent positive outcomes with an
      antivascular endothelial growth factor antibody combined with chemotherapy as
      front-line therapy of metastatic colorectal cancer have renewed enthusiasm for
      this therapeutic strategy. This article presents an overview of experimental and
      clinical studies of combined therapy with antiangiogenic agents and highlights
      the challenges related to the appropriate strategies for selection of the
      patients, study design, and choice of proper end points for preclinical and
      clinical studies using these agents.

PMID- 15718329
TI  - Uncommon presentations of some common malignancies: Case 1. Sequential
      paraneoplastic endocrine syndromes in small-cell lung cancer.

PMID- 15718330
TI  - Uncommon presentations of some common malignancies: Case 2. Nasopharyngeal
      carcinoma followed by secondary acute promyelocytic leukemia presenting with
      respiratory distress.

PMID- 15718331
TI  - Uncommon presentations of some common malignancies: Case 3. Chronic lymphocytic
      leukemia involving the colon and presenting with perforation.

PMID- 15718332
TI  - Role of intraspinal analgesia in terminal pediatric malignancy.

PMID- 15718334
TI  - Watchful waiting, temporarily deferred therapy, or active surveillance?

PMID- 15718335
TI  - Prognostic factors in cytokine-refractory renal cell carcinoma treated with
      irinotecan, Cisplatin, and mitomycin chemotherapy.

PMID- 15718336
TI  - Thalidomide with continuous low-dose dexamethasone for multiple myeloma.

PMID- 15718337
TI  - Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a
      role?

PMID- 15718338
TI  - Targeted therapy for targeted patients: trastuzumab in adjuvant treatment of non
      small-cell lung cancer.

PMID- 15718341
TI  - Prognosis of acute monocytic leukemia (French-American-British classification
      M5).

PMID- 15718342
TI  - Potential antiretroviral drug interactions with cyclophosphamide, Doxorubicin,
      and Etoposide.

PMID- 15718344
TI  - The choice of bilateral prophylactic mastectomy.

PMID- 15718346
TI  - Platelet-derived growth factor receptor inhibitor imatinib mesylate and
      docetaxel: a modular phase I trial in androgen-independent prostate cancer.

PMID- 15718348
TI  - They also serve who only stand and wait: do individual clinical researchers, too?
      Hoping for individual patient data as public domain.

PMID- 15718349
TI  - Toward a clearer understanding of the prognostic value of health-related quality
      of-life parameters in breast cancer.

PMID- 15718351
TI  - Functional brain deficits in congenital central hypoventilation syndrome:
      commentary on the articles by Woo et al. on page 510 and Macey et al. on page
      500.

PMID- 15718352
TI  - Higher concentrations of heparin and hirudin are required to inhibit thrombin
      generation in tissue factor-activated cord plasma than in adult plasma.
AB  - Neonatal plasma clots slower than adult plasma, and only 30-50% of peak adult
      thrombin activity can be produced in neonatal plasma when high amounts of tissue
      factor (TF) are added to trigger clotting, as used in standard clotting assays.
      Plasma activation by addition of low amounts of TF probably better reflects
      conditions in vivo. Under these conditions, cord plasma clots faster than adult
      plasma. In the present study, we show that after activation with low amounts of
      TF, higher amounts of the anticoagulants heparin and hirudin are required in cord
      plasma for effective inhibition of thrombin generation compared with adult
      plasma. After strong activation with high amounts of TF (30 microM), the thrombin
      potential was significantly more suppressed in cord plasma compared with adult
      plasma in the presence of 0.4 IE/mL heparin (-92 versus -75%; p < 0.01) and in
      the presence of 2 IE/mL hirudin (-18 versus -8%; p < 0.01). In contrast, after
      weak activation with low amounts of TF (30 pM), the thrombin potential was
      significantly more suppressed in adult plasma compared with neonatal plasma in
      the presence of 0.025 IE/mL heparin (-93 versus -8%; p < 0.01) and in the
      presence of 2 IE/mL hirudin (-89 versus -48%; p < 0.01). Our results show that in
      neonates, effects of anticoagulants very much depend on the type of activation
      used to initiate clotting, and doses of anticoagulants should not be derived from
      studies done in adults, because potentially higher doses of anticoagulants may be
      required.

PMID- 15718353
TI  - Long-term outcome of bladder augmentation using living-related partial bladder
      transplantation in rats.
AB  - Long-term histopathologic changes after bladder augmentation (BA) in rats using
      living-related partial bladder transplantation (LPBTx) or conventional
      ileocystoplasty (ICP) were compared. In this study, BA (n = 37), LPBTx (n = 18),
      and ICP (n = 19) were performed in 16-wk-old Lewis rats. Five donors and seven
      nontransplanted normal Lewis rats (controls) were also studied. Rats that
      survived >10 mo after BA were killed after blood biochemistry and neobladder
      imaging. Harvested bladders were examined with hematoxylin and eosin and
      proliferating cell nuclear antigen (PCNA). When the rats were killed, there were
      16 rats in the LPBTx group and 12 rats in the ICP group; ICP rats were
      significantly smaller than LPBTx rats (p < 0.05). Mean duration of follow-up for
      the LPBTX group was 17.3 mo, for the ICP group was 13.7 mo, for the donor group
      was 16.1 mo, and for the control group was 19.7 mo. Mean serum pH in the LPBTx
      group was 7.41 +/- 0.78 and in the ICP group was 7.25 +/- 0.38. Mean base excess
      in the ICP group was significantly lower than in the LPBTx group (p < 0.05).
      Incidence of bladder calculi in the LPBTx group (6.3%) was significantly lower
      than in the ICP group (33.3%; p < 0.05). There was no
      dysplasia/malignancy/increase in PCNA in the LPBTx group. PCNA increased in the
      ICP group, compared with controls (p < 0.05); two (16.7%) of 12 of ICP rats had
      dysplasia with mitosis. Bladder capacity increased in LPBTx and ICP compared with
      controls (both p < 0.05). We hope to show that BA using LPBTx may result in a
      neobladder with fewer complications than BA using ICP; LPBTx may also decrease
      the risk for malignancy.

PMID- 15718355
TI  - Impaired cardiac sympathetic nerve function in patients with Kawasaki disease:
      comparison with myocardial perfusion.
AB  - Kawasaki disease (KD) is a leading cause of CAD in children. The impairment of
      cardiac sympathetic nerve function (CSNF) in the adult patients with coronary
      artery disease (CAD) could often be seen. However, little is known concerning the
      impairment of CSNF in KD patients. We investigated CSNF and its relationship with
      myocardial perfusion in KD patients. Eleven children with KD and 4 controls were
      studied with 123I-metaiodobenzylguanidine (MIBG) and stressed 201Tl single photon
      emission computed tomography. By the findings on coronary artery angiography
      (CAG), the patients were divided into 2 groups: A, without stenosis; B, with
      significant stenosis and/or old myocardial infarction. CSNF was evaluated from
      the uptake of 123I-MIBG. While myocardial perfusion was evaluated from 201Tl
      uptake. The numbers of patients in the groups A and B were 7 and 4. Perfusion
      defect was found in 0, and 2 patients in group A (0%), and B (50%). 123I-MIBG
      defects were found in 1 and 4 patients in the group A (14%) and B (100%). There
      were excellent concordances between the finding of 201Tl and 123I-MIBG in group
      A. While in group B, the coronary territories with 123I-MIBG defects were
      significantly more than those with perfusion defects (p < 0.05). In KD patients,
      the impairment of CSNF might be subsequent to coronary artery stenosis and was
      more severe than the injury of myocardial perfusion.

PMID- 15718356
TI  - Body composition in preterm infants who are fed long-chain polyunsaturated fatty
      acids: a prospective, randomized, controlled trial.
AB  - The objective of this study was to evaluate growth and body composition of
      premature infants who were fed formulas with arachidonic acid (ARA; 20:4n6) and
      docosahexaenoic acid (DHA; 22:6n3) to 1 y of gestation-corrected age (CA).
      Preterm infants (750-1800 g birth weight and <33 wk gestational age) were
      assigned within 72 h of first enteral feeding to one of three formulas: control
      (n = 22), DHA+ARA from fish/fungal oil [DHA+ARA(FF); n = 20], or DHA+ARA from
      egg/fish oil [DHA+ARA(EF); n = 18]. Human milk feeding was allowed on the basis
      of the mother's choice. Infants were fed breast milk and/or preterm formulas with
      or without 0.26% DHA and 0.42% ARA to term CA followed by breast milk or
      postdischarge preterm formulas with or without 0.16% DHA and 0.42% ARA to 12 mo
      CA. Body composition was measured by dual-energy x-ray absorptiometry. There were
      no significant differences among the three study groups at any time point in
      weight, length, or head circumference. Bone mineral content and bone mineral
      density did not differ among groups. At 12 mo CA, infants who were fed DHA+ARA
      supplemented formulas had significantly greater lean body mass (p < 0.05) and
      significantly less fat mass (p < 0.05) than infants who were fed the
      unsupplemented control formula. The DHA+ARA-supplemented formulas supported
      normal growth and bone mineralization in premature infants who were born at <33
      wk gestation. Preterm formulas that had DHA+ARA at the levels and ratios in this
      study and were fed to 1 y CA led to increased lean body mass and reduced fat mass
      by 1 y of age.

PMID- 15718357
TI  - The selective class III/V receptor tyrosine kinase inhibitor SU11657 inhibits
      tumor growth and angiogenesis in experimental neuroblastomas grown in mice.
AB  - Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and
      platelet-derived growth factor (PDGF) and their cognate receptor tyrosine kinases
      are strongly implicated in angiogenesis associated with solid tumors. SU11657
      (SUGEN) is a selective multitargeted tyrosine kinase inhibitor with antitumor and
      antiangiogenic activity exerted by targeting PDGF receptors (PDGFR), VEGF
      receptors (VEGFR), stem cell factor receptor (c-KIT), and FMS-related tyrosine
      kinase 3. Oral administration of SU11657 at 40 mg x kg(-1) x d(-1) to athymic
      mice resulted in significant growth inhibition of a panel of s.c. human
      neuroblastoma xenografts, namely, fast-growing SK-N-AS, MYCN- amplified IMR-32,
      and SH-SY5Y, by 90, 93.8, and 88%, respectively, and was well tolerated. All of
      the cell lines expressed VEGFR-2, PDGFR-beta, and c-KIT protein in the tumor cell
      and endothelial cell compartment by immunohistochemistry, and the expression
      decreased during therapy. Plasma concentrations of VEGF-A, PDGF-BB, and stem cell
      factor increased per milliliter of tumor volume at days 10, 18, and 20 of
      therapy. Furthermore, SU11657 reduced tumor angiogenesis by 63-96%. Our
      experimental data suggest that the angiogenesis inhibitor SU11657 may be
      beneficial in the treatment of rapidly growing and highly vascularized solid
      tumors of childhood, such as neuroblastoma. In summary, the class III/V receptor
      tyrosine kinases and their ligands are implicated in angiogenesis, tumor cell
      proliferation, and cell survival, and it seems reasonable to determine whether
      interference with these pathways can suppress neuroblastoma growth or not.

PMID- 15718358
TI  - Brain docosahexaenoic acid status and learning in young rats submitted to dietary
      long-chain polyunsaturated fatty acid deficiency and supplementation limited to
      lactation.
AB  - N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid
      (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning
      disadvantages. The influence of n-3 deficiency and supplementation on brain fatty
      acids and learning were investigated in young rats. Newborn Wistar rats were
      assigned to three groups of cross-foster mothers. The control group (C) was
      nursed by mothers that received essential fatty acids during pregnancy and
      lactation, and the deficient group (D) was nursed by mothers that did not receive
      those fatty acids. The supplemental group (S) had the same conditions as D,
      receiving an additional DHA and arachidonic acid supplement during lactation.
      Cerebral cortex and hippocampus fatty acid composition was examined using thin
      layer and capillary column gas chromatography, and learning was measured by
      passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S
      brain composition was similar to C. Learning in the S group was unaffected, but
      in the D group, it was poorer than C. Learning was directly correlated with DHA
      levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels
      both were correlated with poor learning. DPA seems not to be a suitable brain
      functional analogue of DHA, and DHA supplementation reversed both biochemical and
      learning adverse effects observed in n-3 deficiency.

PMID- 15718359
TI  - Association between erythropoietin in cord blood of twins and size at birth: does
      it relate to gestational factors or to factors during labor or delivery?
AB  - We hypothesized that cord blood erythropoietin (EPO), a marker of fetal hypoxia,
      relates to gestational factors and not solely those associated with delivery. We
      investigated the association between birth weight SD score (SDS) and cord blood
      EPO in 290 twins (145 pairs), assessing the influence of gestational versus
      perinatal factors by comparing the association in those who were delivered by
      elective cesarean (CS) with that in other delivery modes. Blood EPO values were
      skewed, so geometric means are presented and log EPO values were used in
      statistical models. The birth size-EPO association was estimated in mixed-effects
      models that included terms that represented difference in log EPO and mean log
      EPO for each twin pair. Within-pair estimates of the association were
      unconfounded by maternal factors (because these were perfectly controlled).
      Geometric mean EPO was higher in boys versus girls (24.4 versus 17.0 IU/L; p =
      0.0001) and increased with gestational age (p = 0.0003) but was similar after
      elective CS versus other delivery modes. The negative birth size-EPO association
      was stronger in infants who were delivered by elective CS than by other delivery
      modes [beta for log(2) EPO: -0.56 (95% CI, -0.77 to -0.36) versus -0.27 (-0.42 to
      -0.12), respectively; p = 0.02 for interaction). Because the association was seen
      after elective CS delivery, cord blood EPO must relate to factors during
      gestation, not just perinatal factors. There was no evidence of an association
      between birth weight SDS and pair mean log EPO, indicating that the association
      is entirely due to fetus-specific rather than pair-specific factors.

PMID- 15718360
TI  - Risk factors for intrauterine growth restriction: a comparison between two
      Brazilian cities.
AB  - In Brazil, similar intrauterine growth restriction (IUGR) rates were observed
      between cities with distinct levels of socioeconomic development, challenging the
      current knowledge that higher rates of IUGR would necessarily be observed in
      poorer areas than in wealthier ones. Ribeirao Preto, a city located in the most
      developed area in Brazil, showed an IUGR rate of 18% in 1994, whereas this rate
      was 18.5% in 1997/1998 in Sao Luis, located in one of the poorest areas in the
      country. The objective of this study was to compare risk factors for IUGR in
      these two cities and to identify factors that are responsible for this unexpected
      lack of difference between the rates. Using data from two birth cohorts,
      including 2839 neonates who were from Ribeirao Preto and born in 1994 and 2439
      neonates who were from Sao Luis and born in 1997/1998, a multivariable analysis
      was conducted to assess changes in the risk for IUGR in the poorer city compared
      with the wealthier one in a combined model, adjusting for some risk factors for
      IUGR. The wealthier city showed higher rates of maternal smoking, attendance in
      the private sector, and obstetric interventions than the less developed one.
      Differences in maternal smoking and obstetric interventions were possibly
      responsible for the similarity of the rates between cities. It seems that early
      detection of IUGR followed by cesarean section in the wealthier city is
      associated with increased low birth weight and IUGR rates but reduced stillbirth
      and infant mortality rates.

PMID- 15718361
TI  - Spontaneous breathing or mechanical ventilation alters lung compliance and tissue
      association of exogenous surfactant in preterm newborn rabbits.
AB  - In preterm infants with respiratory distress syndrome, surfactant administration
      followed by immediate extubation to spontaneous breathing with nasal continuous
      positive airway pressure reduces the need for mechanical ventilation. With this
      treatment approach, repeated doses of surfactant are rarely indicated. We used a
      rabbit model to test the hypothesis that exogenous surfactant therapy followed by
      spontaneous breathing results in a more sustained initial treatment response
      compared with treatment followed by mechanical ventilation. Preterm rabbits
      (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg
      radiolabeled surfactant (14C-Curosurf) and randomized to 4 h of spontaneous
      breathing or mechanical ventilation or to a control group, killed immediately
      after surfactant administration. With pharyngeal deposition, 46 +/- 10% (mean +/-
      SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax
      compliance was higher in spontaneously breathing compared with mechanically
      ventilated animals (median, 9.9 and 0.75 ml x cm H2O(-1) x kg(-1), respectively;
      p < 0.05). The relative distribution of 14C-Curosurf in bronchoalveolar lavage
      fluid and homogenized lung tissue showed a higher degree of tissue association in
      the spontaneously breathing animals [53 +/- 4 versus 26 +/- 3% (mean +/- SEM)]
      than in mechanically ventilated animals (p < 0.01), the latter figure being very
      similar to that of the control group (25 +/- 5%). There was a higher degree of
      lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from
      mechanically ventilated animals. We conclude that the initial lung tissue
      association of exogenous surfactant is impaired by mechanical ventilation. This
      is associated with a reduction of dynamic compliance and evidence of increased
      surfactant inactivation.

PMID- 15718362
TI  - Characterization of cord blood natural killer cells: implications for
      transplantation and neonatal infections.
AB  - The role of natural killer (NK) cells in hematopoietic stem cell transplantation
      and in the control of neonatal infections is not yet clear. Donor-versus
      recipient NK cell alloreactivity was found to improve outcome in some settings of
      hematopoietic stem cell transplantation. We hypothesized that the role of NK
      cells in cord blood (CB) transplantation and neonatal infections may depend on CB
      NK cell maturation stage. We therefore analyzed the expression of NK cell
      differentiation/phenotypic markers in human CB, as well as functional properties
      of purified CB NK cells. CD8 and CD57 expression was lower in CB than in adult NK
      cells. However, the expression of other differentiation markers was similar, as
      was cell surface density of CD56, the percentage of late NK cell precursors,
      interferon-gamma production, and the proliferative response of purified NK cells
      to IL-2. Spontaneous cytotoxic activity of purified CB NK cells against NK
      sensitive targets was low but reached adult levels after treatment with IL-15.
      Expression of perforin and granzyme B was higher in CB NK cells (90 versus 58%
      and 86 versus 69%, respectively). intercellular adhesion molecule-1 and CD161
      expression was lower in CB. Surprising, fewer CB NK cells expressed L-selectin, a
      marker of immature NK cells. Taken together, our results suggest that CB NK cells
      are phenotypically and functionally mature.

PMID- 15718363
TI  - Granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor have differential effects on neonatal and adult neutrophil
      survival and function.
AB  - Neutropenia is a common sequela of neonatal sepsis. Recent clinical trials have
      shown the beneficial effects of colony-stimulating factors (CSFs) on outcome in
      this group, but the exact mechanism remains unknown. Neonates and mothers who
      were at high-risk for infection were recruited for cord blood sampling in a
      university tertiary referral maternity hospital. Neonatal and adult neutrophils
      were evaluated for their ability to combat bacterial infection by examining their
      functional activity (CD11b and reactive oxygen intermediates) and their
      persistence at inflammatory sites (apoptosis). The mechanism for altered
      apoptotic responses was assessed by caspase activation assays, X chromosome
      linked inhibitor of apoptosis protein expression, and cytosolic cytochrome c
      release. Although granulocyte colony-stimulating factor (G-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) significantly delayed neutrophil
      apoptosis in normal adults, only G-CSF had a similar effect in normal neonates.
      Neutrophils from neonates who are at high risk for infection are unresponsive to
      the antiapoptotic effects of G-CSF or GM-CSF, unlike maternal neutrophils, which
      have delayed apoptosis in response to GM-CSF. However, CD11b expression and
      reactive oxygen intermediate production were significantly increased in normal
      neonatal neutrophils that were incubated with GM-CSF versus controls but not G
      CSF or lipopolysaccharide. Decreased cytosolic cytochrome c release and caspases
      3 and 9 activity are associated with the CSF-mediated delay in apoptosis in
      adults but not in newborns. The antiapoptotic X chromosome-linked inhibitor of
      apoptosis protein is up-regulated in neonates compared with adults and may
      mediate their differential spontaneous apoptosis. These results have important
      implications for the use of CSFs in neonatal sepsis, as responses differ from
      those seen in adults. Further delineation of neonatal neutrophil responses to
      CSFs may improve their therapeutic potential.

PMID- 15718364
TI  - Genetic polymorphisms and cerebral palsy in very preterm infants.
AB  - In the present study, we examine whether selected genetic polymorphisms
      contribute to the development of cerebral palsy (CP) in very preterm infants.
      Subjects were 96 singleton infants with later-diagnosed CP and 119 control
      children, white non-Hispanic (n for CP=74, controls=88) or white Hispanic (CP=22,
      controls=31), born <32 wk gestation. Presence of CP was identified through state
      service agencies, with review of medical records. DNA extracted from archived
      neonatal blood was genotyped using multi-locus polymerase chain reaction
      amplification and immobilized sequence-specific oligonucleotide probes. Single
      nucleotide polymorphisms (SNPs) showing evidence of association with development
      of CP were endothelial nitric oxide synthase (eNOS) A(-922)G, factor 7 (F7)
      arg353gln and del(-323)10bp-ins, and lymphotoxin A (LTA) thr26asn. In white non
      Hispanic children, beta-2 adrenergic receptor gln27glu was associated with CP
      risk; in Hispanic children, plasminogen activator inhibitor-1 (PAI-1) 4G(-675)5G
      and G11053T were associated with risk of CP. In a logistic regression considering
      these SNPs simultaneously in non-Hispanics, an association with CP was observed
      for heterozygotes of eNOS -922 (OR 3.0, CI 1.4-6.4), F7 (OR 2.7, CI 1.1-6.5), LTA
      (OR 2.1, CI 1.0-4.6), and PAI-1 (OR 3.2, CI 1.2-8.7). Factor 5, Factor 2,
      methylene tetrahydrofolate reductase, tumor necrosis factor-alpha, and other SNPs
      tested were not significantly associated with CP risk. We conclude that further
      study of genetic factors that may influence susceptibility to CP in very preterm
      infants is warranted.

PMID- 15718365
TI  - Expression of toll-like receptor 4 and endotoxin responsiveness in mice during
      perinatal period.
AB  - Endotoxin [lipopolysaccharide (LPS)] from Gram-negative bacteria is found in
      amniotic fluid in intrauterine infections that associate with the risk for
      spontaneous premature birth, bronchopulmonary dysplasia (BPD), and respiratory
      distress syndrome. Toll-like receptor 4 (TLR4) is the signaling receptor for LPS.
      The aim was to investigate the primary inflammatory response in mice shortly
      after administration of LPS to the dam (14 and 17 d of pregnancy), to the
      newborn, or into the amniotic fluid. The expression levels of TLR4, IL-1, tumor
      necrosis factor-alpha, IL-6, IL-10, macrophage inflammatory protein-2, and IL-1
      receptor 1 were studied with ribonuclease protection assay. In addition, TLR4
      protein was analyzed with Western blotting. The fetal membranes expressed TLR4
      mRNA and protein and showed an acute cytokine response to LPS when LPS was
      administrated into the amniotic fluid. There was distinct ontogeny in the
      responsiveness of fetal lung to LPS: on fetal day 14 (term 20 d), both the
      expression of TLR4 and the acute cytokine response were undetectable 5 h after
      LPS; they became detectable by fetal day 17. TLR4 and the cytokine response
      further increased after birth. In maternal lung, the TLR4 expression was
      strongest and up-regulated in parallel with the induction of the cytokines. We
      propose that TLR4 controls the magnitude of the LPS-induced cytokine response
      during the perinatal period.

PMID- 15718366
TI  - Effect of dexamethasone on B7 regulation and T cell activation in neonates and
      adults.
AB  - The safety of dexamethasone for neonates has been questioned, partly because of
      its multiple unspecific effects on the immune system. Specific effects of
      dexamethasone on co-stimulatory and immune suppressive functions of neonatal
      compared with adult macrophages (MPhi) are not known. We evaluated the effect of
      dexamethasone on the expression and regulation of MPhi B7 family receptors (B7-1,
      CD80; B7-2, CD86) and on their ability to co-stimulate T cells. Cord blood
      macrophages (CBMPhi) and MPhi from healthy adults (PBMPhi) were isolated, and
      cell surface markers were phenotyped by flow cytometry. In tissue culture, cells
      were exposed to dexamethasone, interferon-gamma (IFN-gamma), cAMP, or a T cell
      mitogen (alphaCD3) and examined for their capacity to activate or destroy T
      cells. CBMPhi were less able to up-regulate CD80 and CD86 than PBMPhi (p < 0.05).
      Dexamethasone inhibited the up-regulation of CD80, CD86, and HLA-DR on PBMPhi and
      even more so on CBMPhi (p < 0.05 versus PBMPhi for CD80 and CD86). In the
      presence of dexamethasone, stimulation with alphaCD3 MAb enhanced cytotoxic
      functions of PMBMPhi and CB(mu)phi with an increase in deleted T cells, a reduced
      fraction of enlarged T cells, and an inhibition of T cell CD28 up-regulation,
      which again were more pronounced with CBMPhi (p < 0.05 versus PBMPhi). In
      conclusion, neonatal MPhi are exquisitely sensitive to the inhibitory effects of
      dexamethasone on B7 expression. Although perhaps producing the desired
      therapeutic effect, dexamethasone may do so in newborns at the expense of a near
      complete paralysis of MPhi-dependent T cell function.

PMID- 15718367
TI  - Cerebral blood flow during spontaneous and cholinergically induced behavioral
      states in the sheep fetus.
AB  - The sleep-wake cycle has been studied extensively in both adult and fetal
      mammalian species with emphasis in different areas. Fetal studies have focused on
      characterization of behavioral states and responses to challenges such as
      hypoxia, and there have been relatively fewer studies that have investigated the
      control of fetal behavioral state. The objective of this study was to determine
      whether cerebral blood flow during cholinergically induced fetal behavioral
      states was similar to that during spontaneous fetal behavioral states in
      chronically catheterized near-term sheep fetuses. Injection of carbachol (1.25
      microg) into the cisterna magna increased the duration of the subsequent low
      voltage electrocortical epoch. Scopolamine infusion (0.3 mg) increased the
      duration of the subsequent high-voltage electrocortical activity epoch. Cerebral
      blood flow and oxygen delivery were higher during both spontaneous and carbachol
      induced low-voltage/rapid eye movement behavioral state than during spontaneous
      and scopolamine-induced high-voltage/non-rapid eye movement behavioral state.
      Thus, pharmacologic manipulation of fetal behavioral state induced a state that
      resembled spontaneous fetal behavioral state both electrophysiologically and
      metabolically. This study shows that inducing extended periods of a desired fetal
      behavioral state is possible and that this method may be used to study their
      function.

PMID- 15718368
TI  - Developmental indices of nutritionally induced placental growth restriction in
      the adolescent sheep.
AB  - Most intrauterine growth restriction cases are associated with reduced placental
      growth. Overfeeding adolescent ewes undergoing singleton pregnancies restricts
      placental growth and reduces lamb birth weight. We used this sheep model of
      adolescent pregnancy to investigate whether placental growth restriction is
      associated with altered placental cell proliferation and/or apoptosis at d 81 of
      pregnancy, equivalent to the apex in placental growth. Adolescent ewes with
      singleton pregnancies were offered a high or moderate level of a complete diet
      designed to induce restricted or normal placental size at term, respectively.
      Bromodeoxyuridine (Brd-U) was administered to H and M ewes 1 h before slaughter.
      Placental tissues were examined for a) Brd-U (immunohistochemistry) and b)
      apoptosis regulatory genes by in situ hybridization, Northern analyses (bax, mcl
      1), immunohistochemistry, and Western analyses (bax). Quantification was carried
      out by image analysis. Total placentome weights were equivalent between groups.
      Brd-U predominantly localized to the trophectoderm and was significantly lower in
      the H group. Bax and mcl-1 mRNA were localized to the maternal-fetal interface.
      Bax protein was significantly increased in the H group and predominant in the
      uninuclear fetal trophectoderm. These observations indicate that reduced
      placental size at term may be due to reduced placental cell proliferation and
      possibly increased apoptosis occurring much earlier in gestation.

PMID- 15718370
TI  - FMRI responses to hyperoxia in congenital central hypoventilation syndrome.
AB  - Congenital Central Hypoventilation Syndrome (CCHS) patients show partial
      retention of peripheral chemoreception despite impaired ventilatory responses to
      CO2 and hypoxia. The condition allows examination of central responses to
      hyperoxia, which minimizes afferent traffic from peripheral chemoreceptors. We
      used functional magnetic resonance imaging to assess blood oxygen level-dependent
      signals over the brain during a baseline and subsequent 2-min hyperoxia (100% O2)
      period in 14 CCHS and 15 control subjects. After partitioning gray matter and
      correcting for global effects, the images were analyzed using volume-of-interest
      time trends followed by repeated-measures ANOVA and conventional cluster
      analyses. Respiratory rates initially (first 20 s) fell in CCHS, but rose in
      control subjects; CCHS heart rate increased in the first minute, and then
      decreased in the second minute, as in controls, but with muted rise and extent of
      decline. Multiple sites within the cerebellum, midbrain, and pons responded
      similarly to the challenge in both groups. Response patterns differed early in
      the right amygdala, paralleling initial respiratory pattern deficits, and late in
      the right insula, concomitant with cardiac rate differences. Signals also
      differed between groups in the medial and anterior cingulate, hippocampus, head
      of caudate, and lentiform nuclei, as well as pontine and midbrain structures and
      regions within the superior temporal and inferior frontal cortical gyri. The
      findings emphasize that structures that can alter respiratory timing, such as the
      amygdala, and modulate sympathetic outflow, such as the right insula, are
      deficient in CCHS. Medullary and pontine areas targeted by PHOX2B expression are
      also affected.

PMID- 15718369
TI  - Is the early development of girls with Rett disorder really normal?
AB  - An apparently normal early development was one of the initial criteria for
      classical Rett syndrome. However, several investigators considered Rett syndrome
      to be a developmental disorder manifesting very soon after birth. Videos of 22
      Rett cases were assessed carefully for movements, posture, and behavior during
      the first 6 mo of life. All signs that deviated from the normal standard were
      recorded meticulously. Special attention was paid to the face, the hands, and
      body movements. A detailed analysis clearly demonstrated an abnormal quality of
      general movements (100%), tongue protrusion (62%), postural stiffness (58%),
      asymmetric eye opening and closing (56%), abnormal finger movements (52%), hand
      stereotypies (42%), bursts of abnormal facial expressions (42%), bizarre smile
      (32%), tremor (28%), and stereotyped body movements (15%). Our study is the first
      to apply specific standardized measures of early spontaneous movements to Rett
      infants, proving conclusively that the disorder is manifested within the first
      months of life. Although not necessarily specific, the signs that we have
      observed will be of value in alerting clinicians to the possibility of the
      diagnosis at an early stage, when intervention is likely to be most effective.

PMID- 15718371
TI  - Responses of pulmonary platelet-derived growth factor peptides and receptors to
      hyperoxia and nitric oxide in piglet lungs.
AB  - The peptides platelet-derived growth factor-A (PDGF-A) and especially -B have
      important roles in lung development. The effect of hyperoxic exposure with and
      without inhaled nitric oxide (iNO) on lung expression of PDGF and its receptors
      is unknown. We hypothesized that hyperoxia exposure would suppress mRNA
      expression and protein production of these ligands and their receptors. The
      addition of iNO to hyperoxia may further aggravate the effects of hyperoxia.
      Thirteen-day-old piglets were randomized to breathe 1) room air (RA); 2) 0.96
      fraction of inspired oxygen (O2), or 3) 0.96 fraction of inspired oxygen plus 50
      ppm of NO (O2+NO), for 5 d. Lungs were preserved for mRNA, Western immunoblot,
      and immunohistochemical analyses for PDGF-A and -B and their receptors PDGFR
      alpha and -beta. PDGF-B mRNA expression was greater than that of PDGF-A or PDGFR
      alpha and -beta in RA piglet lungs (p<0.05). Hyperoxia with or without iNO
      reduced lung PDGF-B mRNA and protein expression relative to the RA group lungs
      (p<0.01). PDGF-B immunostain intensity was significantly increased in the
      alveolar macrophages, which were present in greater numbers in the hyperoxia
      exposed piglet lungs, with or without NO (p<0.01). PDGFR-beta immunostaining was
      significantly increased in airway epithelial cells in O2- and O2+NO-exposed
      piglets. PDGF-A and PDGFR-alpha immunostain intensity and distribution pattern
      were unchanged relative to the RA group. Sublethal hyperoxia decreases PDGF-B
      mRNA and protein expression but not PDGF-A or their receptors in piglet lungs.
      iNO neither aggravates nor ameliorates this effect.

PMID- 15718372
TI  - Altered expression patterns of EphrinB2 and EphB2 in human umbilical vessels and
      congenital venous malformations.
AB  - Vascular malformations cause discomfort and pain in children and are often
      associated with skeletal hypertrophy. Their molecular basis is poorly understood.
      Ephrin ligands and Eph receptor tyrosine kinases are involved in embryonic
      vascular development. In mice, some ephrin/Eph family members show a
      complementary expression pattern in blood vessels, with ephrinB2 being expressed
      on arterial and EphB4 on venous endothelium. Targeted deletions of the genes
      reveal their essential roles for conduit vessel development in mice, suggesting
      similar functions during human vascular development and deregulation in vascular
      malformations. Here, we have defined the expression patterns of human ephrinB2,
      EphB4, and EphB2 in normal vessels of neonates (i.e. umbilici) and adults and
      compared them with those in congenital venous malformations. In adults, normal
      vessels of the skin, muscle, and legs express ephrinB2 and EphB2 on arterial
      endothelial cells (ECs), whereas EphB4 is found in arteries and veins. In the
      umbilicus, EphB2 is a specific marker of arterial ECs, whereas ephrinB2 is
      additionally expressed in venous ECs, suggesting an arterial function of the
      veins. In venous malformations, the expression of EphB4 is not altered, but both
      ephrinB2 and EphB2 are ectopically expressed in venous ECs. This may reflect a
      nonphysiologic arterialization of malformed veins. Our study shows that the
      arterial markers ephrin B2 and EphB2 are expressed in a subset of veins, and it
      remains to be studied whether this is cause or consequence of an altered vascular
      identity.

PMID- 15718373
TI  - Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal
      transducer and activator of transcription signaling pathway and improves brain
      injury in postnatal day 7 rats.
AB  - Erythropoietin (Epo) plays a central role in erythropoiesis but also has
      neuroprotective properties. Recently, Epo-related neuroprotective studies used a
      hypoxic-ischemic neonatal model, which is different from focal stroke, a frequent
      cause of neonatal brain injury. We report on the effects of Epo treatment given
      after focal stroke and its potential neuroprotective mechanisms in postnatal day
      7 rats with focal cerebral ischemia (FCI) achieved by occlusion of the middle
      cerebral artery. The experimental groups included sham operation, FCI plus
      vehicle, and FCI plus Epo. In the Epo-treated group, pups received a single
      intraperitoneal injection of 1000 U/kg 15 min after FCI or three injections of
      100, 1000, or 5000 U/kg, starting at 15 min and repeated at 1 and 2 d after FCI.
      Epo treatment produced significant reductions in the mean infarct area and volume
      at 1 and 3 d after FCI, demonstrated by 2,3,5-triphenyltetrazolium chloride
      staining. Terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'
      triphosphate-biotin nick end labeling (TUNEL) staining showed a markedly reduced
      number of TUNEL-positive cells in the Epo-treated group when compared with the
      vehicle control 3 d after FCI (p<0.01). The most effective dose after FCI was
      1000 U/kg for 3 d. Immunoanalyses showed that Epo induced a significant increase
      in phosphorylated Janus kinase 2 and signal transducer and activator of
      transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24
      h after FCI but did not affect Epo receptor or NF-kappaB expression. In
      conclusion, Epo given after FCI in neonatal rats provides significant
      neuroprotection, mediated possibly by activation of the Janus kinase-signal
      transducer and activator of transcription-Bcl-xL signaling pathways.

PMID- 15718374
TI  - Development of neonatal murine microglia in vitro: changes in response to
      lipopolysaccharide and ischemia-like injury.
AB  - Hypoxic/ischemic brain injury in the neonate can activate an inflammatory
      cascade, which potentiates cellular injury. The role of microglia in this
      inflammatory response has not been studied extensively. We used an in vitro model
      of murine microglia to investigate changes in microglial cytokine release and
      injury during early development. Isolated microglia were subjected to
      lipopolysaccharide (LPS) activation or injury by glucose deprivation (GD), serum
      deprivation (SD), or combined oxygen-glucose deprivation (OGD) for varying
      durations. The extent and the type of cell death were determined by trypan blue,
      terminal deoxynucleotidyl end-nick labeling, and annexin staining. Early-culture
      microglia (2-3 d in purified culture) showed significantly more apoptotic cell
      death after SD, GD, and OGD compared with microglia maintained in culture for 14
      17 d. Measurements of tumor necrosis factor-alpha (TNF-alpha) and IL-1beta in
      culture media demonstrated that OGD induced greater release of both TNF-alpha and
      IL-1beta than LPS activation, with early-culture microglia producing more TNF
      alpha compared with late-culture microglia. Microglia that are cultured for a
      short time are more sensitive to ischemia-like injury in vitro than those that
      are cultured for longer durations and may contribute to worsening brain injury by
      increased release of inflammatory cytokines. Inhibition of microglial activation
      and decreasing proinflammatory cytokine release may be targets for reduction of
      neonatal hypoxic/ischemic brain injury.

PMID- 15718375
TI  - Aberrant neural responses to cold pressor challenges in congenital central
      hypoventilation syndrome.
AB  - Patients with congenital central hypoventilation syndrome (CCHS), a condition
      characterized by impaired ventilatory responses to chemoreceptor stimulation, do
      not show the normal increase in respiratory rate and respiratory-related heart
      rate variation to cold forehead stimulation, a challenge that bypasses central
      chemoreceptors. We hypothesized that a forehead cold pressor challenge would
      reveal abnormal neural response patterns, as assessed by functional magnetic
      resonance imaging, in brain regions that are responsible for the integration of
      cold afferent stimulation with respiratory and cardiovascular output in patients
      with CCHS. Primary sensory thalamic and cortical areas for the forehead showed
      diminished responses in 13 patients with CCHS (ventilator dependent during sleep
      but not waking, no Hirschsprung's disease) compared with 14 control subjects,
      despite initial signal changes in the cortex being similar in both groups.
      Cerebellar cortex and deep nuclei; basal ganglia; and middle to posterior
      cingulate, insular, frontal, and temporal cortices showed reduced signal rises in
      patients with CCHS. Areas within the frontal and anterior cingulate cortices
      exhibited marked signal declines in control subjects but little change in
      patients with CCHS. No response occurred in either group in the dorsal medulla,
      but medial and ventral medullary areas showed enhanced signals in patients with
      CCHS. The cold pressor stimulation did not recruit dorsal medullary sites that
      would be affected by PHOX2B (a mutation of which is associated with the syndrome)
      expression in either group but demonstrated deficient cerebellar and medial
      medullary influences that, by action on rostral sites, may underlie the loss of
      respiratory responses.

PMID- 15718376
TI  - The evolution of neonatology.
AB  - In 1960, the terms "neonatology" and "neonatologist" were introduced. Thereafter,
      an increasing number of pediatricians devoted themselves to full-time
      neonatology. In 1975, the first examination of the Sub-Board of Neonatal
      Perinatal Medicine of the American Board of Pediatrics and the first meeting of
      the Perinatal Section of the American Academy of Pediatrics were held. One of the
      most important factors that improved the care of the neonate was the
      miniaturization of blood samples needed to determine blood gases, serum
      electrolytes, glucose, calcium, bilirubin, and other biochemical measurements.
      Another factor was the ability to provide nutrition intravenously, and the third
      was the maintenance of normal body temperature. The management of respiratory
      distress syndrome improved with i.v. glucose and correction of metabolic
      acidosis, followed by assisted ventilation, continuous positive airway pressure,
      antenatal corticosteroid administration, and the introduction of exogenous
      surfactant. Pharmacologic manipulation of the ductus arteriosus, support of blood
      pressure, echocardiography, and changes in the management of persistent pulmonary
      hypertension, including the use of nitric oxide and extracorporeal membrane
      oxygenation, all have influenced the cardiopulmonary management of the neonate.
      Regionalization of neonatal care; changes in parent-infant interaction; and
      technological changes such as phototherapy, oxygen saturation monitors, and brain
      imaging techniques are among the important advances reviewed in this report. Most
      remarkable, a 1-kg infant who was born in 1960 had a mortality risk of 95% but
      had a 95% probability of survival by 2000. However, errors in neonatology are
      acknowledged, and potential directions for the future are explored.

PMID- 15718377
TI  - Aims of undergraduate physiology education: a view from the University of
      Chicago.
AB  - Physiology may play an important, if not essential role, in a liberal arts
      education because it provides a context for integrating information and concepts
      from diverse biological and extra-biological disciplines. Instructors of
      physiology may aid in fulfilling this role by clarifying the core concepts that
      physiological details exemplify. As an example, presented here are the core
      principles that are the basis for an undergraduate physiology course taught at
      the University of Chicago. The first of these is: Evolution has resulted in
      organisms comprising mechanisms for maintenance, growth, and reproduction,
      despite perturbations of the internal and external environment. Such principles
      necessitate a coupling of physiology to diverse disciplines (i.e., "sciomics")
      and provide a basis for integrating discoveries in other disciplines.

PMID- 15718379
TI  - The locust jump: an integrated laboratory investigation.
AB  - The locust is well known for its ability to jump large distances to avoid
      predation. This class sets out a series of investigations into the mechanisms
      underlying the jump enabling students to bring together information from
      biomechanics, muscle physiology, and anatomy. The nature of the investigation
      allows it to be undertaken at a number of levels of complexity from relatively
      simple comparative observations to detailed analysis of the properties of the
      muscles and the energy storage systems involved in powering the jump. The
      relative size and robustness of the locust make it simple to handle and ideal for
      such investigations.

PMID- 15718378
TI  - "Non-trivial pursuit of physiology".
AB  - This article describes a novel way to conduct a review session that combines
      interactivity, team learning, and peer-to-peer instruction. It uses the format of
      the familiar game "Trivial Pursuit." To facilitate the game process and to
      encourage its use by others, we have developed custom software. It allows an
      instructor to run the game from the podium and to input questions/answers for a
      particular block or other area to be reviewed. In addition to the software
      itself, the online supplement
      (http://advan.physiology.org/cgi/content/full/00031.2004/DC1) contains 100 sample
      questions and answers written for the cardiovascular physiology review session.
      The developed game format and its software add to the arsenal of educational
      tools that can be used to enrich students' learning experiences.

PMID- 15718380
TI  - Cat dissection vs. sculpting human structures in clay: an analysis of two
      approaches to undergraduate human anatomy laboratory education.
AB  - Many human anatomy courses are taught using cat dissection. Alternatives are
      available, but information regarding learning outcomes is incomplete. In 2003,
      approximately 120 undergraduates enrolled in a human anatomy course were assigned
      to one of two treatment groups. In the control group, students performed cat
      dissections (emphasizing isolation and identification) of the muscular,
      digestive, and cardiovascular systems. In the experimental treatment group,
      students built clay sculptures of each human body system. Student learning was
      evaluated by using both low- and high-difficulty questions. On pre- and
      postexperiment control exams, there were no significant differences in student
      performance. On exams after a cat dissection vs. a human-clay sculpting
      experience, the students in the human-clay sculpting treatment group scored
      significantly higher than their classmates in the cat dissection group on both
      the low- and high-difficulty questions. Student attitudes toward dissection and
      taking future human anatomy courses were also measured. There were no differences
      in student attitudes at the beginning of the experiment; afterward, students
      exposed to a cat dissection experience viewed dissection more favorably than
      students in the human-clay sculpting treatment group. There were no treatment
      effects on student willingness to take future human anatomy courses. The
      experimental design makes it difficult to conclude precisely why students
      assigned to the human-clay sculpting experience performed better on exams, but as
      each method was performed in this particular human anatomy course, our data
      indicate that human-clay sculpting may be a viable alternative to cat dissection
      in an anatomy course in which the students focus on human anatomy.

PMID- 15718381
TI  - Blending problem-based learning with Web technology positively impacts student
      learning outcomes in acid-base physiology.
AB  - World Wide Web (Web)-based learning (WBL), problem-based learning (PBL), and
      collaborative learning are at present the most powerful educational options in
      higher education. A blended (hybrid) course combines traditional face-to-face and
      WBL approaches in an educational environment that is nonspecific as to time and
      place. To provide educational services for an undergraduate second-year elective
      course in acid-base physiology, a rich, student-centered educational Web
      environment designed to support PBL was created by using Web Course Tools
      courseware. The course is designed to require students to work in small
      collaborative groups using problem solving activities to develop topic
      understanding. The aim of the study was to identify the impact of the blended WBL
      PBL-collaborative learning environment on student learning outcomes. Student test
      scores and satisfaction survey results from a blended WBL-PBL-based test group (n
      = 37) were compared with a control group whose instructional opportunities were
      from a traditional in-class PBL model (n = 84). WBL students scored significantly
      (t = 3.3952; P = 0.0009) better on the final acid-base physiology examination and
      expressed a positive attitude to the new learning environment in the satisfaction
      survey. Expressed in terms of a difference effect, the mean of the treated group
      (WBL) is at the 76th percentile of the untreated (face-to-face) group, which
      stands for a "medium" effect size. Thus student progress in the blended WBL-PBL
      collaborative environment was positively affected by the use of technology.

PMID- 15718382
TI  - A multimedia CD-ROM tool to improve student understanding of bile salts and
      bilirubin metabolism: evaluation of its use in a medical hybrid PBL course.
AB  - Over the last 35 years our understanding of bile salts, bilirubin metabolism, and
      hepatobiliary transport has progressively increased. From 1965 to the end of
      2002, 3,610 articles and review papers have been published on hepatobiliary and
      enterocyte transport of bile salts. However, there is a lack of information in
      the content of current textbooks about hepatobiliary physiology, bile salt
      transporters, bile formation, mechanisms underlying cholestasis, and drug-induced
      liver injury. The use of an integrated multimedia program on the liver covering
      these gaps in textbooks may be useful to student learning. This study aims to 1)
      assess student views on a multimedia CD-ROM ("The Liver") integrating basic and
      clinical sciences related to the liver, bile salts, and bilirubin metabolism, 2)
      assess the usefulness of problem-based learning (PBL) cases included in the
      multimedia CD-ROM, and 3) assess student learning before and after use of the
      multimedia CD-ROM. A total of 106 first-year medical students (27 with and 79
      without a prior university degree) at the University of Melbourne participated in
      this study. Students were tested on the liver, bile salts, and bilirubin
      metabolism before and after using the multimedia CD-ROM. After completing the
      multimedia CD-ROM, each student filled out a 5-point Likert scale questionnaire
      evaluating the features of the program and its usefulness to their learning.
      Results show that the aims of the package were clear to participants, the
      contents were logically organized and clear, the key concepts were easy to
      identify, the contents were pitched to an appropriate level, and the package was
      interactive and encouraged participants to reflect on their learning. Students
      also agreed that the assessment tools used in the program and the feedback
      provided were meaningful and helpful to their learning. No differences were found
      when responses were compared on the basis of academic background, gender,
      citizenship, or first language of participants. Students agreed that the PBL
      cases in the CD-ROM kept them engaged, were useful to their learning, and matched
      with the overall philosophy of the program. Compared with graduate-entry students
      (those with a prior university degree), school leavers (those with no prior
      university degree) showed a more positive attitude toward the PBL cases included
      in the multimedia CD-ROM and agreed that cases kept them engaged (P = 0.033).
      Students who completed the test after using the multimedia CD-ROM scored higher
      compared with those who completed the test before using the multimedia CD-ROM (P
      < 0.001). In conclusion, using bile salts, bilirubin metabolism, and their
      hepatobiliary transport as an example, the incorporation of a multimedia CD-ROM
      into the first-year medical course has the potential to improve student
      understanding of the main concepts in a variety of body systems.

PMID- 15718383
TI  - Chewing over physiology integration.
AB  - An important challenge for both students and teachers of physiology is to
      integrate the different areas in which physiological knowledge is didactically
      divided. In developing countries, such an issue is even more demanding, because
      budget restrictions often affect the physiology program with laboratory classes
      being the first on the list when it comes to cuts in expenses. With the aim of
      addressing this kind of problem, the graduate students of our department
      organized a physiology summer course offered to undergraduate students. The
      objective was to present the different physiological systems in an integrated
      fashion. The strategy pursued was to plan laboratory classes whose experimental
      results were the basis for the relevant theoretical discussions. The subject we
      developed to illustrate physiology integration was the study of factors
      influencing salivary secretion.

PMID- 15718384
TI  - Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake,
      sham feeding, and gastric emptying in rats.
AB  - Glucagon-like peptide-1(7-36)-amide (GLP-1) is postulated to act as a hormonal
      signal from gut to brain to inhibit food intake and gastric emptying. A mixed
      nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the
      effects of intravenous infusions of GLP-1 on food intake, sham feeding, and
      gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part,
      by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5-170
      pmol.kg(-1).min(-1)) at dark onset dose-dependently inhibited food intake in rats
      that were normally fed with a potency (mean effective dose) and efficacy (maximal
      % inhibition) of 23 pmol.kg(-1).min(-1) and 82%, respectively. Similar total
      doses of GLP-1 administered over a 15-min period were less potent and effective.
      In gastric emptying experiments, GLP-1 (1.7-50 pmol.kg(-1).min(-1)) dose
      dependently inhibited gastric emptying of saline and ingested chow with potencies
      of 18 and 6 pmol.kg(-1).min(-1) and maximal inhibitions of 74 and 83%,
      respectively. In sham-feeding experiments, GLP-1 (5-50 pmol.kg(-1).min(-1)) dose
      dependently reduced 15% aqueous sucrose intake in a similar manner when gastric
      cannulas were closed (real feeding) and open (sham feeding). These results
      demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food
      intake, sham feeding, and gastric emptying with a similar potency and efficacy.
      Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can
      also inhibit food intake independently of its action to reduce gastric emptying.
      It remains to be determined whether intravenous doses of GLP-1 that reproduce
      postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and
      gastric emptying.

PMID- 15718385
TI  - Dehydration anorexia is attenuated in oxytocin-deficient mice.
AB  - Evidence in rats suggests that central oxytocin (OT) signaling pathways
      contribute to suppression of food intake during dehydration (i.e., dehydration
      anorexia). The present study examined water deprivation-induced dehydration
      anorexia in wild-type and OT -/- mice. Mice were deprived of food alone (fasted,
      euhydrated) or were deprived of both food and water (fasted, dehydrated) for 18 h
      overnight. Fasted wild-type mice consumed significantly less chow during a 60-min
      refeeding period when dehydrated compared with their intake when euhydrated.
      Conversely, fasting-induced food intake was slightly but not significantly
      suppressed by dehydration in OT -/- mice, evidence for attenuated dehydration
      anorexia. In a separate experiment, mice were deprived of water (but not food)
      overnight for 18 h; then they were anesthetized and perfused with fixative for
      immunocytochemical analysis of central Fos expression. Fos was elevated similarly
      in osmo- and volume-sensitive regions of the basal forebrain and hypothalamus in
      wild-type and OT -/- mice after water deprivation. OT-positive neurons expressed
      Fos in dehydrated wild-type mice, and vasopressin-positive neurons were activated
      to a similar extent in wild-type and OT -/- mice. Conversely, significantly fewer
      neurons within the hindbrain dorsal vagal complex were activated in OT -/- mice
      after water deprivation compared with activation in wild-type mice. These
      findings support the view that OT-containing projections from the hypothalamus to
      the hindbrain are necessary for the full expression of compensatory behavioral
      and physiological responses to dehydration.

PMID- 15718386
TI  - Mitochondrial permeability transition in the crustacean Artemia franciscana:
      absence of a calcium-regulated pore in the face of profound calcium storage.
AB  - When mammalian mitochondria are exposed to high calcium and phosphate, a massive
      swelling, uncoupling of respiration, and release of cytochrome c occur. These
      changes are mediated by opening of the mitochondrial permeability transition pore
      (MPTP). Activation of the MPTP in vivo in response to hypoxic and oxidative
      stress leads to necrotic and apoptotic cell death. Considering that embryos of
      the brine shrimp Artemia franciscana tolerate anoxia for years, we investigated
      the MPTP in this crustacean to reveal whether pore opening occurs. Minimum
      molecular constituents of the regulated MPTP in mammals are believed to be the
      voltage-dependent anion channel, the adenine nucleotide translocators, and
      cyclophilin D. Western blot analysis revealed that mitochondria from A.
      franciscana possess all three required components. When measured with a calcium
      sensitive fluorescent probe, rat liver mitochondria are shown to release matrix
      calcium after addition of >/=100 microM extramitochondrial calcium (MPTP
      opening), whereas brine shrimp mitochondria continue to take up
      extramitochondrial calcium and do not release internal stores even up to 1.0 mM
      exogenously added calcium (no MPTP opening). Furthermore, no swelling of A.
      franciscana mitochondria in response to added calcium was observed, and no
      release of cytochrome c could be detected. HgCl(2)-dependent swelling and
      cytochrome c release were readily confirmed, which is consistent with the
      presence of an "unregulated pore." Although the absence of a regulated MPTP in A.
      franciscana mitochondria could contribute to the extreme hypoxia tolerance in
      this species, we speculate that absence of the regulated MPTP may be a general
      feature of invertebrates.

PMID- 15718387
TI  - Cytosolic phospholipase A2alpha regulates induction of brain cyclooxygenase-2 in
      a mouse model of inflammation.
AB  - The products of arachidonic acid metabolism are key mediators of inflammatory
      responses in the central nervous system, and yet we do not know the mechanisms of
      their regulation. The phospholipase A(2) enzymes are sources of cellular
      arachidonic acid, and the enzymes cyclooxygenase-2 (COX-2) and microsomal PGE
      synthase-1 (mPGES-1) are essential for the synthesis of inflammatory PGE(2) in
      the brain. These studies seek to determine the function of cytosolic
      phospholipase A(2)alpha (cPLA(2)alpha) in inflammatory PGE(2) production in the
      brain. We wondered whether cPLA(2)alpha functions in inflammation to produce
      arachidonic acid or to modulate levels of COX-2 or mPGES-1. We investigated these
      questions in the brains of wild-type mice and mice deficient in cPLA(2)alpha
      (cPLA(2)alpha(-/-)) after systemic administration of LPS. cPLA(2)alpha(-/-) mice
      had significantly less brain COX-2 mRNA and protein expression in response to LPS
      than wild-type mice. The reduction in COX-2 was most apparent in the cells of the
      cerebral blood vessels and the leptomeninges. The brain PGE(2) concentration of
      untreated cPLA(2)alpha(-/-) mice was equal to their wild-type littermates. After
      LPS treatment, however, the brain concentration of PGE(2) was significantly less
      in cPLA(2)alpha(-/-) than in cPLA(2)alpha(+/+) mice (24.4 +/- 3.8 vs. 49.3 +/-
      11.6 ng/g). In contrast to COX-2, mPGES-1 RNA levels increased equally in both
      mouse genotypes, and mPGES-1 protein was unaltered 6 h after LPS. We conclude
      that cPLA(2)alpha regulates COX-2 levels and modulates inflammatory PGE(2)
      levels. These results indicate that cPLA(2)alpha inhibition is a novel anti
      inflammatory strategy that modulates, but does not completely prevent, eicosanoid
      responses.

PMID- 15718388
TI  - Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney.
AB  - The syndrome of apparent mineralocorticoid excess (SAME) is an autosomal
      recessive form of salt-sensitive hypertension caused by deficiency of the kidney
      type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2). In this disorder,
      cortisol is not inactivated by 11betaHSD2, occupies mineralocorticoid receptors
      (MRs), and causes excessive sodium retention and hypertension. In renal medulla,
      prostaglandins derived from cyclooxygenase-2 (COX-2) stimulate sodium and water
      excretion, and renal medullary COX-2 expression increases after mineralocorticoid
      administration. We investigated whether medullary COX-2 also increases in rats
      with 11betaHSD2 inhibition and examined its possible role in the development of
      hypertension. 11betaHSD2 inhibition increased medullary and decreased cortical
      COX-2 expression in adult rats and induced high blood pressure in high-salt
      treated rats. COX-2 inhibition had no effect on blood pressure in control animals
      but further increased blood pressure in high-salt-treated rats with 11betaHSD2
      inhibition. COX-1 inhibition had no effect on blood pressure in either control or
      experimental animals. 11betaHSD2 inhibition also led to medullary COX-2 increase
      and cortical COX-2 decrease in weaning rats, primarily through activation of MRs.
      In the suckling rats, medullary COX-2 expression was very low, consistent with a
      urinary concentrating defect. 11betaHSD2 inhibition had no effect on either
      cortical or medullary COX-2 expression in the suckling rats, consistent with low
      levels of circulating corticosterone in these animals. These data indicate that
      COX-2 plays a modulating role in the development of hypertension due to
      11betaHSD2 deficiency and that 11betaHSD2 regulates renal COX-2 expression by
      preventing glucocorticoid access to MRs during postnatal development.

PMID- 15718389
TI  - Corticosterone suppresses mesenteric lymph node T cells by inhibiting p38/ERK
      pathway and promotes bacterial translocation after alcohol and burn injury.
AB  - Previous studies showed that alcohol (EtOH) intoxication before burn injury
      suppresses mesenteric lymph node (MLN) T cell functions and increases gut
      bacterial translocation. In this study, we examined whether corticosterone (Cort)
      plays any role in suppressing MLN T cell function and bacterial accumulation
      after EtOH intoxication and burn injury. Rats were gavaged with EtOH to achieve a
      blood EtOH level of approximately 100 mg/dl before receiving 25% total body
      surface area burn or sham injury. A group of rats was treated with the Cort
      synthesis inhibitor metyrapone (25 mg/kg) at the time of injury and on day 1
      after injury. Two days after injury, a significant increase in blood Cort levels
      and suppression of MLN T cell proliferation and IL-2 production was observed in
      rats receiving combined insult of EtOH intoxication and burn injury compared with
      rats receiving EtOH intoxication or burn injury alone. There was no change in T
      cell apoptosis after combined insult of EtOH and burn injury. Furthermore, T cell
      suppression was accompanied by a significant decrease in p38 and ERK1/2
      activation (phosphorylation). There was no difference in JNK activation after
      EtOH and burn injury. Treatment of rats with metyrapone prevented the suppression
      of MLN T cell proliferation, IL-2 production, and p38 and ERK1/2 phosphorylation.
      Restoration of T cell function in metyrapone-treated animals was also associated
      with the decrease in bacterial accumulation in MLN. These findings suggest that
      EtOH intoxication before burn injury augments Cort release, which suppresses MLN
      T cell function by inhibiting p38 and ERK1/2 activation and promotes bacterial
      accumulation in MLN after EtOH and burn injury.

PMID- 15718390
TI  - Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced
      suppression of intake.
AB  - Ondansetron, a selective serotonin-type 3 (5-HT(3)) receptor antagonist, was used
      to test the hypothesis that duodenal infusion of isosmotic solutions of Polycose
      or its hydrolytic product glucose suppressed intake through 5-HT(3) receptors.
      Polycose suppressed sucrose intake across both concentrations infused (132 mM,
      7.6 +/- 0.6 ml; 263 mM, 2.3 +/- 0.5 ml), compared with intake under control
      conditions (12.6 +/- 0.3 ml, P <0.001). Pretreatment with 1.0 mg/kg ondansetron
      attenuated reduction of sucrose intake induced only by the highest concentration
      of Polycose (4.6 +/- 0.8 ml, P = 0.004). Dose-response testing revealed that
      suppression of food intake by 263 mM Polycose was equally attenuated by
      ondansetron administered at 1.0, 2.0, and 5.0 mg/kg but not when given at 0.125,
      0.25, and 0.5 mg/kg. Acarbose, an alpha-glucosidase inhibitor, attenuated
      Polycose-induced suppression of food intake, and pretreatment with 1.0 mg/kg
      ondansetron had no further effect. Suppression of intake after 990 mM glucose but
      not mannitol infusion was attenuated by pretreatment with 1.0 mg/kg ondansetron.
      The competitive SGLT(1) inhibitor, phloridzin, had no effect on 60-min 990 mM
      glucose-induced suppression of intake or the ability of ondansetron to attenuate
      this suppression of intake. Conversely, glucose-induced suppression of intake was
      attenuated by phloridzin at earlier time points and further attenuated when rats
      were pretreated with 1.0 mg/kg ondansetron. Ondansetron administration alone had
      no effect on intake at any dose tested. We conclude that 5-HT(3) receptors
      participate in the inhibition of food intake by intraduodenal infusion of
      carbohydrate solutions through a posthydrolytic, preabsorptive mechanism.

PMID- 15718391
TI  - Adenosine and ATP-sensitive potassium channels modulate dopamine release in the
      anoxic turtle (Trachemys scripta) striatum.
AB  - Excessive dopamine (DA) is known to cause hypoxic/ischemic damage to mammalian
      brain. The freshwater turtle Trachemys scripta, however, maintains basal striatal
      DA levels in anoxia. We investigated DA balance during early anoxia when energy
      status in the turtle brain is compromised. The roles of ATP-sensitive potassium
      (K(ATP)) channels and adenosine (AD) receptors were investigated as these factors
      affect DA balance in mammalian neurons. Striatal extracellular DA was determined
      by microdialysis with HPLC in the presence or absence of the specific DA
      transport blocker GBR-12909, the K(ATP) blocker 2,3-butanedione monoxime, or the
      nonspecific AD receptor blocker theophylline. We found that in contrast to long
      term anoxia, blocking DA reuptake did not significantly increase extracellular
      levels in 1-h anoxic turtles. Low DA levels in early anoxia were maintained
      instead by activation of K(ATP) channels and AD receptors. Blocking K(ATP)
      resulted in a 227% increase in extracellular DA in 1-h anoxic turtles but had no
      effect after 4 h of anoxia. Similarly, blocking AD receptors increased DA during
      the first hour of anoxia but did not change DA levels at 4-h anoxia. Support for
      the role of K(ATP) channels in DA balance comes from normoxic animals treated
      with K(ATP) opener; infusing diazoxide but not adenosine into the normoxic turtle
      striatum resulted in an immediate DA decrease to 14% of basal values within 1.5
      h. Alternative strategies to maintain low extracellular levels may prevent
      catastrophic DA increases when intracellular energy is compromised while
      permitting the turtle to maintain a functional neuronal network during long-term
      anoxia.

PMID- 15718392
TI  - Deterministic construct of amplifying actions of ghrelin on pulsatile growth
      hormone secretion.
AB  - Ghrelin is a native ligand for the growth hormone secretagogue (GHS) receptor
      that stimulates pulsatile GH secretion markedly. At present, no formal construct
      exists to unify ensemble effects of ghrelin, GH-releasing hormone (GHRH),
      somatostatin (SRIF), and GH feedback. To model such interactions, we have assumed
      that ghrelin can stimulate pituitary GH secretion directly, antagonize inhibition
      of pituitary GH release by SRIF, oppose suppression of GHRH neurons in the
      arcuate nucleus (ArC) by SRIF, and induce GHRH secretion from ArC. The dynamics
      of such connectivity yield self-renewable GH pulse patterns mirroring those in
      the adult male and female rat and explicate the following key experimental
      observations. 1) Constant GHS infusion stimulates pulsatile GH secretion. 2) GHS
      and GHRH display synergy in vivo. 3) A systemic pulse of GHS stimulates GH
      secretion in the female rat at any time and in the male more during a spontaneous
      peak than during a trough. 4) Transgenetic silencing of the neuronal GHS receptor
      blunts GH pulses in the female. 5) Intracerebroventricular administration of GHS
      induces GH secretion. The minimal construct of GHS-GHRH-SRIF-GH interactions
      should aid in integrating physiological data, testing regulatory hypotheses, and
      forecasting innovative experiments.

PMID- 15718393
TI  - Resonance in a mathematical model of baroreflex control: arterial blood pressure
      waves accompanying postural stress.
AB  - A mathematical model of the arterial baroreflex was developed and used to assess
      the stability of the reflex and its potential role in producing the low-frequency
      arterial blood pressure oscillations called Mayer waves that are commonly seen in
      humans and animals in response to decreased central blood volume. The model
      consists of an arrangement of discrete-time filters derived from published
      physiological studies, which is reduced to a numerical expression for the
      baroreflex open-loop frequency response. Model stability was assessed for two
      states: normal and decreased central blood volume. The state of decreased central
      blood volume was simulated by decreasing baroreflex parasympathetic heart rate
      gain and by increasing baroreflex sympathetic vaso/venomotor gains as occurs with
      the unloading of cardiopulmonary baroreceptors. For the normal state, the
      feedback system was stable by the Nyquist criterion (gain margin = 0.6), but in
      the hypovolemic state, the gain margin was small (0.07), and the closed-loop
      frequency response exhibited a sharp peak (gain of 11) at 0.07 Hz, the same
      frequency as that observed for arterial pressure fluctuations in a group of
      healthy standing subjects. These findings support the theory that stresses
      affecting central blood volume, including upright posture, can reduce the
      stability of the normally stable arterial baroreflex feedback, leading to
      resonance and low-frequency blood pressure waves.

PMID- 15718394
TI  - Attenuation of aortic baroreflex responses by microinjections of endomorphin-2
      into the rostral ventrolateral medullary pressor area of the rat.
AB  - The presence of mu-opioid receptors and endomorphins has been demonstrated in the
      general area encompassing the rostral ventrolateral medullary pressor area
      (RVLM). This investigation was carried out to test the hypothesis that
      endomorphins in the RVLM may have a modulatory role in regulating cardiovascular
      function. Blood pressure and heart rate (HR) were recorded in urethane
      anesthetized male Wistar rats. Unilateral microinjections of endomorphin-2
      (0.0125-0.5 mmol/l) into the RVLM elicited decreases in mean arterial pressure
      (16-30 mmHg) and HR (12-36 beats/min), which lasted for 2-4 min. Bradycardia was
      not vagally mediated. The effects of endomorphin-2 were mediated via mu-opioid
      receptors because prior microinjections of naloxonazine (1 mmol/l) abolished
      these responses; the blocking effect of naloxonazine lasted for 15-20 min.
      Unilateral stimulations of aortic nerve for 30 s (at frequencies of 5, 10, and 25
      pulses/s; each pulse 0.5 V and 1-ms duration) elicited depressor and bradycardic
      responses. These responses were significantly attenuated by microinjections of
      endomorphin-2 (0.2 and 0.4 mmol/l). The inhibitory effect of endomorphin-2 on
      baroreflex responses was prevented by prior microinjections of naloxonazine.
      Microinjections of naloxonazine alone did not affect either baseline blood
      pressure and HR or baroreflex responses. These results indicate that endomorphin
      2 elicits depressor and bradycardic responses and inhibits baroreflex function
      when injected into the RVLM. These effects are consistent with the known
      hyperpolarizing effect of opioid peptides on RVLM neurons.

PMID- 15718395
TI  - The predictive value of sperm chromatin structure assay.

PMID- 15718396
TI  - Support for the contention that sperm with abnormal sperm chromatin structure
      assays are associated with reduced embryo implantation potential.

PMID- 15718397
TI  - 'Flushing with lipiodol for unexplained (and endometriosis-related) subfertility
      by hysterosalpingography'.

PMID- 15718398
TI  - Length-tension relationships are altered in regenerating muscles of the rat after
      bupivacaine injection.
AB  - Intramuscular injection of bupivacaine causes complete degeneration of fibers in
      extensor digitorum longus (EDL) muscles of rats, followed by complete
      regeneration within 60 days. Previous studies have shown that regenerated EDL
      muscles are protected from contraction-induced injury 60 days after bupivacaine
      injection. It is possible that these regenerated muscles have altered length
      tension relations because of fiber remodeling. We tested the hypothesis that
      length-tension relations are different in bupivacaine-injected and noninjected
      control muscles. EDL and soleus muscles of the right hindlimb of deeply
      anesthetized rats were injected with bupivacaine and then allowed to recover for
      7, 14, 21, or 60 days (7D, 14D, 21D, 60D), and isometric contractile properties
      were assessed. Muscles of the contralateral limb were not injected and served as
      control. EDL muscles recovered from bupivacaine injection more rapidly than
      soleus muscles, with mass restored to control levels at 21D, and isometric
      tetanic force (P(o)) restored to control at 60D. In contrast, mass and P(o) of
      injected soleus muscles was not restored to control even at 60D. In 7D EDL
      muscles, length-tension curves were shifted leftward compared with control, but
      in 21D and 60D EDL muscles length-tension curves were right shifted significantly
      (treatment x muscle length: P < 0.001). Although no clear shift in the position
      of the length-tension curve was observed in regenerating soleus muscles, force
      production was enhanced on the descending limb of the curve in 60D soleus muscles
      (treatment x relative muscle length: P < 0.01). The rightward shift in the length
      tension curve of EDL muscles 60 days after bupivacaine injection is likely to
      contribute to the mechanism for their previously observed protection from
      contraction-induced injury.

PMID- 15718399
TI  - Laryngeal chemoreflexes induced by acid, water, and saline in nonsedated newborn
      lambs during quiet sleep.
AB  - Laryngeal chemoreflexes (LCR) are triggered by the contact of assorted liquids
      with the laryngeal mucosa. In the neonatal period, the immature LCR consist
      primarily of apnea and bradycardia, which at times can be life threatening. The
      aim of this study was to assess LCR induction in nonsedated, newborn full-term
      lambs by several acid solutions, compared with distilled water and saline. Twelve
      lambs were instrumented for recording of glottal adductor and diaphragm EMG, EEG,
      eye movements, heart rate, systemic arterial pressure, and respiratory movements.
      LCR were induced during quiet sleep by the injection (0.5 ml) of saline,
      distilled water or two acid solutions (HCl and citric acid, pH 2, diluted in
      either water or saline). A chronic supraglottal catheter was used to inject the
      solutions in a random order. Distilled water and acid solutions did not induce
      any significant decrease in heart rate or respiratory rate. However, significant
      lower airway protective responses (swallowing, cough, and arousal) were observed
      after distilled water and especially acid solution administration. In conclusion,
      LCR in full-term lambs, particularly with acid solutions, are merely
      characterized by lower airway protective responses resembling mature LCR reported
      in adult mammals.

PMID- 15718400
TI  - Expression and localization of caveolins during postnatal development in rat
      heart: implication of thyroid hormone.
AB  - Caveolins modulate signaling pathways involved in cardiac development. Caveolin-1
      exists in two isoforms: the beta-isoform derivates from an alternative
      translational start site that creates a protein truncated by 31 amino acids,
      mainly expressed in endothelial cells, whereas caveolin-3 is present in muscle
      cells. Our aim was to define caveolin distribution and expression during cardiac
      postnatal development using immunofluorescence and Western blotting. Caveolin-3
      sarcolemmal labeling appeared as dotted lines from days 1 to 5 and as continuous
      lines after 14 days of age. Caveolin-3 expression, low at birth, increased (4
      fold) to reach a maximum (P < 0.05) by day 5 and then decreased to stabilize in
      adults. Total caveolin-1 and its alpha-isoform were codistributed at birth in
      endothelial and smooth muscle cells; afterward, only the caveolin-1alpha labeling
      became limited to endothelium. Quantitative analysis indicated a similar temporal
      pattern of both total caveolin-1 and caveolin-1alpha expression, suggesting that
      caveolin-1alpha and -1beta are coregulated; the caveolin-1alpha levels increased
      fourfold by day 5 to reach a maximum by day 14 (P < 0.05). Tyrosine-14-caveolin-1
      phosphorylation, low at birth, increased suddenly around day 14 (8-fold vs. day
      1) and returning afterward to basal level. Because the T3/T4 level is maximal by
      day 14, caveolin-1 expression/phosphorylation profiles were analyzed in
      hypothyroid heart. The levels of caveolin-1alpha and consequently tyrosine-14
      caveolin-1 phosphorylation, but not that of caveolin-3, decreased (50%) in
      hypothyroid 14-day-old rats. Our data demonstrate that, during postnatal cardiac
      growth, 1) caveolins are distinctly regulated, and 2) thyroid hormones are
      involved in caveolin-1alpha expression.

PMID- 15718401
TI  - Heterogeneous limb vascular responsiveness to shear stimuli during dynamic
      exercise in humans.
AB  - Arm and leg vascular responsiveness to comparable shear stimuli during isolated
      dynamic exercise has not been assessed in humans. Consequently, six young
      cyclists performed incremental, intermittent handgrip exercise (arm) and knee
      extensor exercise (leg) from 5 to 60% of maximal work rate (WR). Ultrasound
      Doppler measurements were taken in the brachial artery (BA), common femoral
      artery (CFA), and deep femoral artery (DFA) at rest and at each WR to assess
      diameter and sheer rate changes. Exercise at 60% maximum WR increased shear rate
      to the same degree in the CFA (314.3 +/- 33.3 s(-1)) and BA (303.3 +/- 26.3 s(
      1)), but was significantly higher in the DFA (712.6 +/- 88.3 s(-1)). Compared
      with rest, exercise at 60% maximum WR did not alter CFA vessel diameter, but
      increased BA diameter (0.42 +/- 0.01 to 0.49 +/- 0.01 cm) and DFA diameter (0.59
      +/- 0.05 to 0.64 +/- 0.04 cm). These data from the DFA demonstrate for the first
      time a substantial improvement in vascular reactivity in a conduit vessel only
      slightly distal to the CFA. However, despite comparable dilation between the BA
      and DFA, the slope of the relationship between vessel diameter and shear rate was
      much greater in the arm (2.4 x 10(-4) +/- 4.6 x 10(-5) cm/s) than in either the
      DFA (8.9 x 10(-5) +/- 1.5 x 10(-5) cm/s) or CFA (2.1 x 10(-5) +/- 1.1 x 10(-5)
      cm/s). Together, these findings reveal a substantial heterogeneity in vascular
      responsiveness in the leg during dynamic exercise but demonstrate that conduit
      vessel dilation for a given change in shear rate is, nonetheless, reduced in the
      leg compared with the arm.

PMID- 15718402
TI  - Skeletal muscle fatigue, strength, and quality in the elderly: the Health ABC
      Study.
AB  - We examined the muscle fatigue characteristics in older men and women and
      determined whether these were related to the size, strength, or quality of
      muscle. A total of 1,512 men and women aged 70-79 yr from the Health, Aging, and
      Body Composition Study participated in this study. Muscle cross-sectional area
      and attenuation were determined with computed tomography. Skeletal muscle fatigue
      and strength (peak torque) of the knee extensors and flexors were measured using
      isokinetic dynamometry. Men were more fatigue resistant than women for both knee
      extension (fatigue index: 70.4 +/- 15.3 vs. 66.9 +/- 14.3%; P < 0.05) and knee
      flexion (67.9 +/- 16.4 vs. 64.9 +/- 17.6%; P < 0.05). Peak torque and muscle
      quality (specific torque) were higher in men than women for knee extension (99.6
      +/- 28.2 vs. 63.0 +/- 16.8 N x m and 1.62 +/- 0.43 vs. 1.51 +/- 0.39 N x m/cm2;
      both P < 0.05) and for knee flexion (74.0 +/- 26.4 vs. 49.6 +/- 15.9 N x m and
      2.47 +/- 1.29 vs. 2.22 +/- 0.78 N x m/cm2; both P < 0.05). Total work and power
      output was greater in men compared with women for both the quadriceps (1,353 +/-
      451 vs. 832 +/- 264 J and 87.7 +/- 33.5 vs. 53.3 +/- 19.2 W; both P < 0.05) and
      the hamstrings (741 +/- 244 vs. 510 +/- 141 J and 35.4 +/- 16.0 vs. 23.7 +/- 10.2
      W; both P < 0.05). In both genders, the quadriceps was able to perform more work
      with greater power compared with the hamstrings. Those who were stronger actually
      had greater fatigue after adjusting for age, race, physical activity, and total
      body fat. In conclusion, older men were more fatigue resistant than women,
      although in both men and women greater fatigue was not related to muscle
      weakness.

PMID- 15718403
TI  - Residual heterogeneity of intra- and interregional pulmonary perfusion in short
      term microgravity.
AB  - We hypothesized that the perfusion heterogeneity in the human, upright lung is
      determined by nongravitational more than gravitational factors. Twelve and six
      subjects were studied during two series of parabolic flights. We used cardiogenic
      oscillations of O(2)/SF(6) as an indirect estimate of intraregional perfusion
      heterogeneity (series 1) and phase IV amplitude (P(4)) as a indirect estimate of
      interregional perfusion heterogeneity (series 2). A rebreathing-breath holding
      expiration maneuver was performed. In flight, breath holding and expiration were
      performed either in microgravity (0 G) or in hypergravity. Controls were
      performed at normal gravity (1 G). In series 1, expiration was performed at 0 G.
      Cardiogenic oscillations of O(2)/SF(6) were 19% lower when breath holding was
      performed at 0 G than when breath holding was performed at 1 G [means (SD): 1.7
      (0.3) and 2.3 (0.6)% units] (P = 0.044). When breath holding was performed at 1.8
      G, values did not differ from 1-G control [2.6 (0.8)% units, P = 0.15], but they
      were 17% larger at 1.8 G than at 1 G. In series 2, expiration was performed at
      1.7 G. P(4) changed with gravity (P < 0.001). When breath holding was performed
      at 0 G, P(4) values were 45 (46)% of control. When breath holding was performed
      at 1.7 G, P(4) values were 183 (101)% of control. We conclude that more than one
      half of indexes of perfusion heterogeneity at 1 G are caused by nongravitational
      mechanisms.

PMID- 15718404
TI  - In vivo evaluation of the effectiveness of bronchial thermoplasty with computed
      tomography.
AB  - A recent study has reported that the application of thermal energy delivered
      through a bronchoscope (bronchial thermoplasty) impairs the ability of airway
      smooth muscle to shorten in response to methacholine (MCh)(Danek CJ, Lombard CM,
      Dungworth DL, Cox PG, Miller JD, Biggs MJ, Keast TM, Loomas BE, Wizeman WJ, Hogg
      JC, and Leff AR. J Appl Physiol 97: 1946-1953, 2004). If such a technique is
      successful, it has the potential to serve as a therapy to attenuate airway
      narrowing in asthmatic subjects regardless of the initiating cause that
      stimulates the smooth muscle. In the present study, we have applied high
      resolution computed tomography to accurately quantify the changes in airway area
      before and after a standard MCh aerosol challenge in airways treated with
      bronchial thermoplasty. We studied a total of 193 airways ranging from 2 to 15 mm
      in six dogs. These were divided into treated and control populations. The MCh
      dose-response curves in untreated airways and soon-to-be-treated airways were
      superimposable. In contrast, the dose-response curves in treated airways were
      shifted upward at all points, showing a significantly decreased sensitivity to
      MCh at both 2 and 4 wk posttreatment. These results thus show that treated
      airways have significantly increased luminal area at any dose of inhaled MCh
      compared with untreated airways. The work in this study thus supports the
      underlying concept that impairing the smooth muscle may be an effective treatment
      for asthma.

PMID- 15718405
TI  - ACTN3 genotype is associated with increases in muscle strength in response to
      resistance training in women.
AB  - The alpha-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers,
      and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3
      genotype (R577X) has been found to be associated with performance in Australian
      elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S,
      and North K. Am J Hum Genet 73: 627-631, 2003). We studied associations between
      ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via
      magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1
      repetition maximum (1-RM)] strength in a large group of men (N = 247) and women
      (N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance
      training program of the nondominant arm at one of eight study centers. We found
      no association between ACTN3 R577X genotype and muscle phenotype in men. However,
      women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared
      with heterozygotes (P < 0.05) when adjusted for body mass and age. Women
      homozygous for the mutant allele (577X) demonstrated greater absolute and
      relative 1-RM gains compared with the homozygous wild type (RR) after resistance
      training when adjusted for body mass and age (P < 0.05). There was a trend for a
      dose-response with genotype such that gains were greatest for XX and least for
      RR. Significant associations were validated in at least one ethnic subpopulation
      (Caucasians, Asians) and were independent of training volume. About 2% of
      baseline MVC and of 1-RM strength gain after training were attributable to ACTN3
      genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one
      of many genes contributing to genetic variation in muscle performance and
      adaptation to exercise.

PMID- 15718406
TI  - New approach to the statistical analysis of cardiovascular data.
AB  - Fourier-based approaches to analysis of variability of R-R intervals or blood
      pressure typically compute power in a given frequency band (e.g., 0.01-0.07 Hz)
      by aggregating the power at each constituent frequency within that band. This
      paper describes a new approach to the analysis of these data. We propose to
      partition the blood pressure variability spectrum into more narrow components by
      computing power in 0.01-Hz-wide bands. Therefore, instead of a single measure of
      variability in a specific frequency interval, we obtain several measurements. The
      approach generates a more complex data structure that requires a careful account
      of the nested repeated measures. We briefly describe a statistical methodology
      based on generalized estimating equations that suitably handles this more complex
      data structure. To illustrate the methods, we consider systolic blood pressure
      data collected during psychological and orthostatic challenge. We compare the
      results with those obtained using the conventional methods to compute blood
      pressure variability, and we show that our approach yields more efficient results
      and more powerful statistical tests. We conclude that this approach may allow a
      more thorough analysis of cardiovascular parameters that are measured under
      different experimental conditions, such as blood pressure or heart rate
      variability.

PMID- 15718407
TI  - Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression
      in human diaphragm.
AB  - We have previously demonstrated that human diaphragm remodeling elicited by
      severe chronic obstructive pulmonary disease (COPD) is characterized by a fast-to
      slow myosin heavy chain isoform transformation. To test the hypothesis that COPD
      induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the
      sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), the other major ATPase in
      skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from
      10 severe COPD patients and 10 control subjects. We then used isoform-specific
      monoclonal antibodies to characterize diaphragm fibers with respect to the
      expression of SERCA isoforms. Compared with control diaphragms, COPD diaphragms
      exhibited a 63% decrease in fibers expressing only fast SERCA (i.e., SERCA1; P <
      0.001), a 190% increase in fibers containing both fast and slow SERCA isoforms (P
      < 0.01), and a 19% increase (P < 0.05) in fibers expressing only the slow SERCA
      isoform (i.e., SERCA2). Additionally, immunoblot experiments carried out on
      diaphragm homogenates indicated that COPD diaphragms expressed only one-third the
      SERCA1 content noted in control diaphragms; in contrast, COPD and control
      diaphragms did not differ with respect to SERCA2 content. The combination of
      these histological and immunoblot results is consistent with the hypothesis that
      diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow
      SERCA isoform transformation. Moreover, the combination of these SERCA data and
      our previously reported myosin heavy chain isoform data (Levine S, Nguyen T,
      Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and
      Shrager JB. Am J Respir Crit Care Med 168: 706-713, 2003) suggests that diaphragm
      remodeling elicited by severe COPD should decrease ATP utilization by the
      diaphragm.

PMID- 15718408
TI  - Increased sympathetic and decreased parasympathetic cardiovascular modulation in
      normal humans with acute sleep deprivation.
AB  - Cardiovascular autonomic modulation during 36 h of total sleep deprivation (SD)
      was assessed in 18 normal subjects (16 men, 2 women, 26.0 +/- 4.6 yr old). ECG
      and continuous blood pressure (BP) from radial artery tonometry were obtained at
      2100 on the first study night (baseline) and every subsequent 12 h of SD. Each
      measurement period included resting supine, seated, and seated performing
      computerized tasks and measured vigilance and executive function. Subjects were
      not supine in the periods between measurements. Spectral analysis of heart rate
      variability (HRV) and BP variability (BPV) was computed for cardiac
      parasympathetic modulation [high-frequency power (HF)], sympathetic modulation
      [low-frequency power (LF)], sympathovagal balance (LF/HF power of R-R
      variability), and BPV sympathetic modulation (at LF). All spectral data were
      expressed in normalized units [(total power of the components/total power-very
      LF) x 100]. Spontaneous baroreflex sensitivity (BRS), based on systolic BP and
      pulse interval powers, was also measured. Supine and sitting, BPV LF was
      significantly increased from baseline at 12, 24, and 36 h of SD. Sitting, HRV LF
      was increased at 12 and 24 h of SD, HRV HF was decreased at 12 h SD, and HRV
      LF/HF power of R-R variability was increased at 12 h of SD. BRS was decreased at
      24 h of SD supine and seated. During the simple reaction time task (vigilance
      testing), the significantly increased sympathetic and decreased parasympathetic
      cardiac modulation and BRS extended through 36 h of SD. In summary, acute SD was
      associated with increased sympathetic and decreased parasympathetic
      cardiovascular modulation and decreased BRS, most consistently in the seated
      position and during simple reaction-time testing.

PMID- 15718409
TI  - Novel method for in vivo hydroxyl radical measurement by microdialysis in fetal
      sheep brain in utero.
AB  - Hydroxyl radical (.OH) is a reactive oxygen species produced during severe
      hypoxia, asphyxia, or ischemia that can cause cell death resulting in brain
      damage. Generation of .OH may occur in the fetal brain during asphyxia in utero.
      The very short half-life of .OH requires use of trapping agents such as salicylic
      acid or phenylalanine for detection, but their hydroxylated derivatives are
      either unstable, produced endogenously, or difficult to measure in the small
      volume of microdialysis samples. In the present study, we used terephthalic acid
      (TA), hydroxylation of which yields a stable and highly fluorometric isomer
      (excitation, 326 nm; emission, 432 nm). In vitro studies using .OH generated by
      the Fenton reaction showed that hydroxylated TA formed quickly (<10 s), was
      resistant to bleaching (<5% change in fluorescence), and permitted detection of
      <0.5 pmol .OH. In vivo studies were performed in fetal sheep using microdialysis
      probes implanted into the parasagittal cortex. The probe was perfused at 2
      mul/min with artificial cerebrospinal fluid containing 5 mM TA, and samples were
      collected every 30 min. Fluorescence measured in 10 mul of dialysate was
      significantly greater than in the efflux from probes perfused without TA. High
      performance liquid chromotography analysis showed that the fluorescence in
      dialysis samples was entirely due to hydroxylation of TA. Thus this study shows
      that it is possible to use TA as a trapping agent for detecting low
      concentrations of .OH both in vitro and in vivo and that low concentrations of
      .OH are present in fetal brain tissue and fluctuate with time.

PMID- 15718410
TI  - Voluntary exercise training enhances glucose transport but not insulin signaling
      capacity in muscle of hypertensive TG(mREN2)27 rats.
AB  - Male heterozygous TG(mREN2)27 rats (TGR) overexpress a murine renin transgene,
      display marked hypertension, and have insulin resistance of skeletal muscle
      glucose transport and insulin signaling. We have shown previously that voluntary
      exercise training by TGR improves insulin-mediated skeletal muscle glucose
      transport (Kinnick TR, Youngblood EB, O'Keefe MP, Saengsirisuwan V, Teachey MK,
      and Henriksen EJ. J Appl Physiol 93: 805-812, 2002). The present study evaluated
      whether this training-induced enhancement of muscle glucose transport is
      associated with upregulation of critical insulin signaling elements, including
      insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase, Akt, and
      glycogen synthase kinase-3. TGR remained sedentary or ran spontaneously in
      activity wheels for 6 wk, averaging 7.1 +/- 0.8 km/day by the end of week 3 and
      4.3 +/- 0.5 km/day over the final week of training. Exercise training reduced
      total abdominal fat by 20% (P < 0.05) in TGR runners (2.64 +/- 0.01% of body
      weight) compared with sedentary TGR controls (3.28 +/- 0.01%). Insulin-stimulated
      (2 mU/ml) glucose transport activity in soleus muscle was 36% greater in TGR
      runners compared with sedentary TGR controls. However, the protein expression and
      functionality of tyrosine phosphorylation of insulin receptor and IRS-1, IRS-1
      associated with the p85 regulatory subunit of phosphatidylinositol 3-kinase, and
      Ser473 phosphorylation of Akt were not altered by exercise training. Only insulin
      stimulated glycogen synthase kinase-3beta Ser9 phosphorylation was increased
      (22%) by exercise training. These results indicate that voluntary exercise
      training in TGR can enhance insulin-mediated glucose transport in skeletal
      muscle, as well as reduce total abdominal fat mass. However, this adaptive
      response in muscle occurs independently of modifications in the proximal elements
      of the insulin signaling cascade.

PMID- 15718411
TI  - Progesterone increases plasma volume independent of estradiol.
AB  - Adequate plasma volume (PV) and extracellular fluid (ECF) volume are essential
      for blood pressure and fluid regulation. We tested the hypotheses that combined
      progesterone (P(4))-estrogen (E(2)) administration would increase ECF volume with
      proportional increases in PV, but that P(4) would have little independent effect
      on either PV or ECF volume. We further hypothesized that this P(4)-E(2)-induced
      fluid expansion would be a function of renin-angiotensin-aldosterone system
      stimulation. We suppressed P(4) and E(2) with a gonadotropin-releasing hormone
      (GnRH) antagonist in eight women (25 +/- 2 yr) for 16 days; P(4) (200 mg/day) was
      added for days 5-16 (P(4)) and 17beta-estradiol (2 x 0.1 mg/day patches) for days
      13-16 (P(4)-E(2)). On days 2 (GnRH antagonist), 9 (P(4)), and 16 (P(4)-E(2)), we
      estimated ECF and PV. To determine the rate of protein and thus water movement
      across the ECF, we also measured transcapillary escape rate of albumin. In P(4),
      P([P(4)]) increased from 2.5 +/- 1.3 to 12.0 +/- 2.8 ng/ml (P < 0.05) with no
      change in P([E(2)]) (21.5 +/- 9.4 to 8.6 +/- 2.0 pg/ml). In P(4)-E(2), plasma
      concentration of P(4) remained elevated (11.3 +/- 2.7 ng/ml) and plasma
      concentration of E(2) increased to 254.1 +/- 52.7 pg/ml (P < 0.05). PV increased
      during P(4) (46.6 +/- 2.5 ml/kg) and P(4)-E(2) (48.4 +/- 3.9 ml/kg) compared with
      GnRH antagonist (43.3 +/- 3.2 ml/kg; P < 0.05), as did ECF (206 +/- 19, 244 +/-
      25, and 239 +/- 27 ml/kg for GnRH antagonist, P(4), and P(4)-E(2), respectively;
      P < 0.05). Transcapillary escape rate of albumin was lowest during P(4)-E(2) (5.8
      +/- 1.3, 3.5 +/- 1.7, and 2.2 +/- 0.4%/h for GnRH antagonist, P(4), and P(4)
      E(2), respectively; P < 0.05). Serum aldosterone increased during P(4) and P(4)
      E(2) compared with GnRH antagonist (79 +/- 17, 127 +/- 13, and 171 +/- 25 pg/ml
      for GnRH antagonist, P(4), and P(4)-E(2), respectively; P < 0.05), but plasma
      renin activity and plasma concentration of ANG II were only increased by P(4)
      E(2). This study is the first to isolate P(4) effects on ECF; however, the
      mechanisms for the ECF and PV expansion have not been clearly defined.

PMID- 15718412
TI  - Acute effects of resistance exercise on arterial compliance.
AB  - Decreased central arterial compliance is an emerging risk factor for
      cardiovascular disease. Resistance training is associated with reductions in the
      elastic properties of central arteries. Currently, it is not known whether this
      reduction is from one bout of resistance exercise or from an adaptation to
      multiple bouts of resistance training. Sixteen healthy sedentary or
      recreationally active adults (11 men and 5 women, age 27 +/- 1 yr) were studied
      under parallel experimental conditions on 2 separate days. The order of
      experiments was randomized between resistance exercise (9 resistance exercises at
      75% of 1 repetition maximum) and sham control (seated rest in the exercise room).
      Baseline hemodynamic values were not different between the two experimental
      conditions. Carotid arterial compliance (via simultaneous B-mode ultrasound and
      applanation tonometry) decreased and beta-stiffness index increased (P < 0.01)
      immediately and 30 min after resistance exercise. Immediately after resistance
      exercise, carotid systolic blood pressure increased (P < 0.01), although no
      changes were observed in brachial systolic blood pressure at any time points.
      These measures returned to baseline values within 60 min after the completion of
      resistance exercise. No significant changes in these variables were observed
      during the sham control condition. These results indicate that one bout of
      resistance exercise acutely decreases central arterial compliance, but this
      effect is sustained for <60 min after the completion of resistance exercise.

PMID- 15718413
TI  - Mantle-cell lymphoma genotypes identified with CGH to BAC microarrays define a
      leukemic subgroup of disease and predict patient outcome.
AB  - To identify recurrent genomic changes in mantle cell lymphoma (MCL), we used high
      resolution comparative genomic hybridization (CGH) to bacterial artificial
      chromosome (BAC) microarrays in 68 patients and 9 MCL-derived cell lines. Array
      CGH defined an MCL genomic signature distinct from other B-cell lymphomas,
      including deletions of 1p21 and 11q22.3-ATM gene with coincident 10p12-BMI1 gene
      amplification and 10p14 deletion, along with a previously unidentified loss
      within 9q21-q22. Specific genomic alterations were associated with different
      subgroups of disease. Notably, 11 patients with leukemic MCL showed a different
      genomic profile than nodal cases, including 8p21.3 deletion at tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) receptor gene cluster (55%
      versus 19%; P = .01) and gain of 8q24.1 at MYC locus (46% versus 14%; P = .015).
      Additionally, leukemic MCL exhibited frequent IGVH mutation (64% versus 21%; P =
      .009) with preferential VH4-39 use (36% versus 4%; P = .005) and followed a more
      indolent clinical course. Blastoid variants, increased number of genomic gains,
      and deletions of P16/INK4a and TP53 genes correlated with poorer outcomes, while
      1p21 loss was associated with prolonged survival (P = .02). In multivariate
      analysis, deletion of 9q21-q22 was the strongest predictor for inferior survival
      (hazard ratio [HR], 6; confidence interval [CI], 2.3 to 15.7). Our study
      highlights the genomic profile as a predictor for clinical outcome and suggests
      that "genome scanning" of chromosomes 1p21, 9q21-q22, 9p21.3-P16/INK4a, and
      17p13.1-TP53 may be clinically useful in MCL.

PMID- 15718414
TI  - Leukotrienes enhance the bactericidal activity of alveolar macrophages against
      Klebsiella pneumoniae through the activation of NADPH oxidase.
AB  - Leukotrienes (LTs) are lipid mediators that participate in inflammatory diseases
      and innate immune function. We sought to investigate the importance of LTs in
      regulating the microbicidal activity of alveolar macrophages (AMs) and the
      molecular mechanisms by which this occurs. The role of LTs in enhancing AM
      microbicidal activity was evaluated pharmacologically and genetically using in
      vitro challenge with Klebsiella pneumoniae. Exogenous LTs increased AM
      microbicidal activity in a dose- and receptor-dependent manner, and endogenous
      production of LTs was necessary for optimal killing. Leukotriene B4 (LTB4) was
      more potent than cysteinyl LTs. An important role for nicotinamide adenine
      dinucleotide (NADPH) oxidase in LT-induced microbicidal activity was indicated by
      the fact that bacterial killing was abrogated by the NADPH oxidase inhibitor
      diphenyleneiodonium (DPI; 10 microM) and in AMs derived from gp91phox-deficient
      mice. By contrast, LT-induced microbicidal activity was independent of the
      generation of nitric oxide. LTs increased H2O2 production, and LTB4 was again the
      more potent agonist. Both classes of LTs elicited translocation of p47phox to the
      cell membrane, and LTB4 induced phosphorylation of p47phox in a manner dependent
      on protein kinase C-delta (PKC-delta) activity. In addition, the enhancement of
      microbicidal activity by LTs was also dependent on PKC-delta activity. Our
      results demonstrate that LTs, especially LTB4, enhanceAM microbicidal activity
      through the PKC-delta-dependent activation of NADPH oxidase.

PMID- 15718415
TI  - Identification of carboxypeptidase N as an enzyme responsible for C-terminal
      cleavage of stromal cell-derived factor-1alpha in the circulation.
AB  - The chemokine stromal-derived factor-1alpha (SDF-1alpha) is an essential
      regulator of hematopoiesis, lymphocyte homing, pre-B-cell growth, and
      angiogenesis. As SDF-1alpha is constitutively expressed in many tissues,
      chemokine function is mostly regulated by proteolytic degradation. Human serum
      cleaves the 68-amino acid chemokine, SDF-1alpha, at both termini. The enzyme or
      enzymes responsible for the removal of the carboxy-terminal lysine from SDF
      1alpha, leading to significant reduction in biologic activity, have not been
      identified. Using a new biochemical assay for measuring the carboxy-terminal
      cleavage activity, we purified from serum and plasma a peptidase that
      specifically removes the carboxy-terminal lysine from SDF-1alpha and identified
      it as carboxypeptidase N (CPN, also known as kininase I, arginine
      carboxypeptidase, and anaphylotoxin inactivator). We demonstrate that SDF-1alpha
      in serum and plasma lacks the carboxy terminal lysine, and depletion of CPN from
      serum and plasma significantly reduces the SDF-1alpha carboxypeptidase activity.
      Purified CPN effectively and specifically removes the carboxy-terminal lysine
      from SDF-1alpha and significantly reduces the chemokine's biologic activity as a
      pre-B-cell growth factor and chemoattractant. Thus, in addition to its role as a
      regulator of the biologic activity of kinins and anaphylatoxins, CPN is an
      important regulator of the biologic activity of SDF-1alpha by reducing the
      chemokine-specific activity.

PMID- 15718416
TI  - B-cell recovery following rituximab-based therapy is associated with
      perturbations in stromal derived factor-1 and granulocyte homeostasis.
AB  - The occurrence of delayed neutropenia following rituximab is poorly defined and
      of unknown cause. We hypothesized it may be related to perturbations of stromal
      derived factor-1 (SDF-1) and granulocyte homeostasis. Late-onset neutropenia
      (LON) was investigated in 130 patients with untreated aggressive B-cell lymphoma
      receiving DA-EPOCH (dose-adjusted etoposide, prednisone, Oncovin [vincristine],
      cyclophosphamide, and hydroxydaunorubicin) chemotherapy with or without
      rituximab. All patients were in remission and had no known causes for
      neutropenia. LON occurred in 6 (8%) of 76 patients receiving rituximab and 0 of
      54 patients not receiving rituximab (P = .04). The median onset was 175 days
      (range, 77-204 days) after treatment with a median duration of 14 days (range, 11
      16 days). In a subset of 24 patients, a significant correlation was found between
      rapid B-cell recovery and granulocyte decline over the 6-month recovery period (R
      = -0.53; P = .04). Rapid B-cell recovery directly correlated with prerecovery SDF
      1 levels (R = 0.65; P = .015) and SDF-1 decline (R = -0.67; P = .013) after
      recovery. Our results suggest that early B-cell lymphopoiesis is important for B
      cell recovery following rituximab, and that perturbation of SDF-1 during B-cell
      recovery retards neutrophil egress from the bone marrow. These findings
      illustrate the dual role of SDF-1 in human B-cell and granulocyte homeostasis.

PMID- 15718417
TI  - Human chronic lymphocytic leukemia B cells can escape DNA damage-induced
      apoptosis through the nonhomologous end-joining DNA repair pathway.
AB  - Nonhomologous end-joining (NHEJ) DNA factors maintain genomic stability through
      their DNA double-strand break (DSB) repair and telomere-associated activities.
      Unrepaired or misrepaired DSBs can lead to apoptotic death or chromosomal damage.
      The B cells of some B-chronic lymphocytic leukemia (B-CLL) patients are resistant
      to radiation-induced apoptosis in vitro. We show here that the novel DNA
      dependent protein kinase (DNA-PK) inhibitor, NU7026 (2-(morpholin-4-yl)
      benzo[h]chomen-4-one), and the phosphatidylinositol 3 (PI-3) kinase inhibitor,
      wortmannin, restored sensitivity to DNA damage-induced apoptosis of otherwise
      resistant cells. These resistant malignant B cells also escaped DSB-induced
      apoptosis following exposure to etoposide or neocarzinostatin. We found that at
      15 minutes after irradiation, the levels of NHEJ (as measured by an in vitro DSB
      end-ligation assay) and DNA-PK catalytic subunit (DNA-PKcs) activity were,
      respectively, 2-fold and 4-fold higher in radio-resistant than in radio-sensitive
      B-CLL cells or Epstein-Barr virus (EBV)-transformed B cells. Ku70/Ku80
      heterodimer DNA end-binding activity was also 2- to 3-fold higher in the
      resistant B-CLL cell subset compared with the sensitive B-CLL cell subset. Our
      results provide the first evidence that overactivating the NHEJ DNA repair
      pathway impairs DNA damage-induced apoptosis in malignant B cells and that this
      may contribute to their resistance to current chemotherapy.

PMID- 15718418
TI  - Identification and characterization of undifferentiated mast cells in mouse bone
      marrow.
AB  - Sequential immunomagnetic isolation with 2 monoclonal antibodies was used to
      purify and characterize an undifferentiated mast cell in adult mouse bone marrow
      that had not been previously recognized. This cell represents 0.02% of the cells
      in the bone marrow, is CD34(+), CD13(+), and c-kit(+), and does not express
      FcepsilonRI. However, by polymerase chain reaction (PCR) the cell contains
      message for the alpha and beta subunits of FcepsilonRI, mast cell-specific
      proteases, and carboxypeptidase A. Morphologically, this cell has a large
      nucleus, little cytoplasm, few cytoplasmic organelles, and no cytoplasmic
      granules. In vitro, in the presence of interleukin-3 (IL-3) and stem cell factor
      (SCF) these cells differentiate only into a granulated mast cell that now
      expresses CD13, c-kit, mast cell-specific gangliosides, FcepsilonRI, and binds
      immunoglobulin E (IgE). When injected into lethally irradiated mice, these cells
      are able to reconstitute the mast cell population in the spleen.

PMID- 15718419
TI  - Gaucher disease and cancer incidence: a study from the Gaucher Registry.
AB  - Patients with Gaucher disease (GD) are alleged to be at an increased risk of
      malignant disorders, possibly due to potential chronic stimulation of the immune
      system and lymphoproliferation associated with storage of glucocerebroside in
      tissue macrophages. Because previous reports of increased risk of malignancy in
      GD may have been affected by small patient numbers and ascertainment bias, 2742
      patients with GD from the International Gaucher Registry were studied. The number
      of cancers identified among patients in the registry was compared with that
      expected in the US population of similar attained age and sex. The majority of
      patients were young or middle-aged adults at the time of last follow-up, with
      only 14% older than age 60. There were 10 patients with multiple myeloma,
      yielding an estimated relative risk of 5.9 (95% confidence interval [95% CI]:
      2.8, 10.8). The relative risk of cancer overall was 0.79 (95% CI: 0.67, 0.94),
      and the subgroups for cancers of the breast, prostate, colon and rectum, lung,
      and hematologic malignancies other than myeloma did not yield statistically
      significant higher risks. This study suggests that, in general, patients with
      Gaucher disease are not at highly increased risk of cancer, at least during early
      and middle age. However, there appears to be a significantly higher risk of
      multiple myeloma of which physicians should be aware when caring for these
      patients.

PMID- 15718420
TI  - FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a
      murine bone marrow transplantation model.
AB  - Activating mutations of the Fms-like tyrosine kinase 3 (FLT3) receptor are the
      most common genetic alteration in acute myeloid leukemia (AML). Two distinct
      groups of FLT3 mutations are found: internal tandem duplications (ITDs) of the
      juxtamembrane region and point mutations within the tyrosine kinase domain (TKD).
      Recently, point mutations within the activation loop of FLT3 have also been
      described in childhood acute lymphoblastic leukemia (ALL). FLT3-ITD has been
      shown to induce a myeloproliferative syndrome in a murine bone marrow
      transplantation model. The phenotype of FLT3-TKD in mice has not yet been
      investigated. We transduced murine bone marrow with retrovirus-expressing FLT3
      TKD mutants or FLT3-ITD and transplanted these cells into lethally irradiated
      mice. Mice that received a transplant of FLT3-ITD developed an oligoclonal
      myeloproliferative disease as previously described. In contrast, FLT3-TKD mutants
      induced an oligoclonal lymphoid disorder with longer latency and distinct
      hematologic manifestations: importantly, induction of the lymphoid phenotype was
      not due to a low number of transplanted cells. The lymphoid manifestation and
      longer latency of FLT3-TKD compared with FLT3-ITD mutants together with the lack
      of influence of FLT3-TKD mutations on the clinical outcome of patients with AML
      suggest differences in cell signaling between FLT3-TKD mutants and FLT3-ITDs.
      Indeed strong signal transducers and activators of transcription 5 (STAT5)
      activation could only be demonstrated for FLT3-ITDs.

PMID- 15718421
TI  - Human embryonic stem cells maintained in the absence of mouse embryonic
      fibroblasts or conditioned media are capable of hematopoietic development.
AB  - To date, hematopoietic development of human embryonic stem cells (hESCs) has been
      limited to cell lines cultured in the presence of either mouse embryonic
      fibroblasts (MEFs) or MEF-conditioned media (MEF-CM). Anonymous xenogenic factors
      from MEFs or MEF-CM complicate studies of hESC self-renewal and also raise
      concerns for the potential clinical applications of generating primitive
      hematopoietic cells from hESC lines maintained under these ambiguous conditions.
      Here, we demonstrate that hESCs can be cultured over 30 passages in defined
      conditions in the absence of MEFs or MEF-CM using only serum replacement (SR)
      media and high concentrations of basic fibroblast growth factor (SR-bFGF).
      Similar to hESCs cultured in MEF-CM, hESCs cultured in SR-bFGF sustained
      characteristics of undifferentiated hESCs, proliferative potential, normal
      karyotype, in vitro and in vivo 3 germ-layer specification and gave rise to
      hemogenic-endothelial precursors required for subsequent primitive hematopoietic
      development. Our report demonstrates that anonymous factors produced by feeder
      cells are not necessary for hESC maintenance and subsequent hematopoietic
      specification, thereby providing a defined system for studies of hESC self
      renewal and hESC-derived hematopoiesis.

PMID- 15718422
TI  - Asparagine synthetase expression is linked with L-asparaginase resistance in TEL
      AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia.
AB  - Resistance to L-asparaginase in leukemic cells may be caused by an elevated
      cellular expression of asparagine synthetase (AS). Previously, we reported that
      high AS expression did not correlate to L-asparaginase resistance in TEL-AML1
      positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we
      confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays.
      In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients
      had a significant 3.5-fold higher AS expression than 43 sensitive patients (P <
      .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this
      finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage
      ALL patients (P = .03). High expression of AS was associated with poor prognosis
      (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with
      low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to
      l-asparaginase and relapse risk are associated with high expression of AS in TEL
      AML1-negative but not TEL-AML1-positive B-lineage ALL.

PMID- 15718424
TI  - Hypoxia-driven proliferation of human pulmonary artery fibroblasts: cross-talk
      between HIF-1alpha and an autocrine angiotensin system.
AB  - Pulmonary artery adventitial fibroblasts (FBPA) may play a central role in lung
      vascular remodeling under conditions of hypoxia and inflammation, the result
      being pulmonary hypertension and cor pulmonale. In cultured human FBPA, both
      angiotensin II (Ang II) and hypoxia promoted cell cycle progression and cell
      proliferation and suppressed apoptosis. These effects were further enhanced when
      both stimuli were applied simultaneously. Hypoxia elevated the expression of
      hypoxia-inducible factor 1alpha (HIF-1alpha) and increased the expression of
      genes regulated by the hypoxia-responsive element (HRE). Up-regulation of both
      angiotensin-converting enzyme (ACE) and Ang II receptor type 1 (AT1) was also
      observed. Exogenous Ang II further increased HIF/HRE-dependent signaling in FBPA,
      whereas suppression of the autocrine ACE-Ang II-AT1 loop with inhibitors of ACE,
      AT1, and phosphatidylinositol 3-kinase (PI3K) reduced the proliferative response
      to both hypoxia and exogenous Ang II. Overexpression of HIF-1alpha by transient
      transfection caused the same proliferative effect and up-regulation of AT1
      expression that were observed under hypoxic conditions. In contrast, small
      interfering RNA targeting HIF-1alpha inhibited hypoxia-induced ACE and AT1
      expression. Our studies indicate that the ACE-Ang II-AT1 system serves as a
      positive feedback loop and fosters FBPA proliferation under hypoxic conditions,
      with the PI3K-HIF-HRE axis as the central effector pathway. This pathway may thus
      facilitate vascular remodeling under hypoxic conditions.

PMID- 15718425
TI  - Spectral reflectance and morphologic correlations in eastern Terra Meridiani,
      Mars.
AB  - The Mars Express Observatoire pour la Mineralogie, l'Eau, les Glaces, et
      l'Activite (OMEGA) hyperspectral image data covering eastern Terra Meridiani
      indicate the ubiquitous presence of molecular water in etched terrain materials
      that disconformably overlie heavily cratered terrains and underlie the hematite
      bearing plains explored by the Opportunity rover. Identification of crystalline
      water in kieserite (MgSO4.H2O) is linked to materials exposed in a valley and
      plateau to the north of hematite-bearing plains. The mineralogical similarities
      between the etched terrain deposits examined with OMEGA data and the layered
      rocks examined by Opportunity imply that the ancient aqueous environments
      inferred from analyses of the rover data extend over regional scales.

PMID- 15718423
TI  - Cell death of bioenergetically compromised and transcriptionally challenged CLL
      lymphocytes by chlorinated ATP.
AB  - Myeloid cell leukemia-1 (MCL-1) acts as a key survival factor for chronic
      lymphocytic leukemia (CLL) cells. In addition, dissipation of cellular bioenergy
      may impose a lethal effect on these quiescent cells. Previously, in multiple
      myeloma cell lines we demonstrated that halogenated adenosine (8-Cl-Ado) was
      phosphorylated to triphosphate (8-Cl-adenosine triphosphate [ATP]), which
      preferentially incorporated into mRNA and inhibited RNA synthesis by premature
      transcription termination. Furthermore, 8-Cl-ATP accumulation was associated with
      a decline in cellular bioenergy. Based on these actions, we hypothesized that 8
      Cl-Ado would be ideal to target CLL lymphocytes. In the present study we
      demonstrate that leukemic lymphocytes incubated with 8-Cl-Ado display time- and
      dose-dependent increase in the accumulation of 8-Cl-ATP, with a parallel
      depletion of the endogenous ATP pool. Inhibition of global RNA synthesis resulted
      in a significant decline in the expression of transcripts with a short half-life
      such as MCL1. Consistent to this, protein expression of MCL-1 but not B-cell
      lymphoma-2 (BCL-2) was decreased. Furthermore, 8-Cl-ATP induced programmed cell
      death, as suggested by caspases activation, cleavage of caspase 3, and PARP (poly
      adenosine diphosphate [ADP]-ribose polymerase), and increased DNA fragmentation.
      In conclusion, 8-Cl-Ado induces apoptosis in CLL lymphocytes by targeting
      cellular bioenergy as well as RNA transcription and translation of key survival
      genes such as MCL1.

PMID- 15718426
TI  - Summer evolution of the north polar cap of Mars as observed by OMEGA/Mars
      Express.
AB  - The Observatoire pour la Mineralogie, l'Eau, les Glaces, et l'Activite (OMEGA)
      visible-infrared imaging spectrometer extensively observed regions of Mars with
      latitudes above 70 degrees N in late 2004 (heliocentric longitude from Ls 93
      degrees to Ls 127 degrees ). The extent of water ice at the surface and the size
      of ice grains were monitored as a function of time. Bright, small-grained frost,
      which initially covered a large fraction of the polar cap, waned in favor of
      large-grained ice. In outlying regions, dominated by large-grained ice, the
      albedo increased over the period. Evaluating the dust content was model
      dependent. However, contamination of ice by dust was low.

PMID- 15718428
TI  - Sulfates in the north polar region of Mars detected by OMEGA/Mars Express.
AB  - The Observatoire pour la Mineralogie, l'Eau, les Glaces, et l'Activite (OMEGA)
      imaging spectrometer observed the northern circumpolar regions of Mars at a
      resolution of a few kilometers. An extended region at 240 degrees E, 85 degrees
      N, with an area of 60 kilometers by 200 kilometers, exhibits absorptions at
      wavelengths of 1.45, 1.75, 1.94, 2.22, 2.26, and 2.48 micrometers. These
      signatures can be unambiguously attributed to calcium-rich sulfates, most likely
      gypsum. This region corresponds to the dark longitudinal dunes of Olympia
      Planitia. These observations reveal that water alteration played a major role in
      the formation of the constituting minerals of northern circumpolar terrains.

PMID- 15718427
TI  - Olivine and pyroxene diversity in the crust of Mars.
AB  - Data from the Observatoire pour la Mineralogie, l'Eau, les Glaces, et l'Activite
      (OMEGA) on the Mars Express spacecraft identify the distinct mafic, rock-forming
      minerals olivine, low-calcium pyroxene (LCP), and high-calcium pyroxene (HCP) on
      the surface of Mars. Olivine- and HCP-rich regions are found in deposits that
      span the age range of geologic units. However, LCP-rich regions are found only in
      the ancient Noachian-aged units, which suggests that melts for these deposits
      were derived from a mantle depleted in aluminum and calcium. Extended dark
      regions in the northern plains exhibit no evidence of strong mafic absorptions or
      absorptions due to hydrated materials.

PMID- 15718429
TI  - Sulfates in Martian layered terrains: the OMEGA/Mars Express view.
AB  - The OMEGA/Mars Express hyperspectral imager identified hydrated sulfates on light
      toned layered terrains on Mars. Outcrops in Valles Marineris, Margaritifer Sinus,
      and Terra Meridiani show evidence for kieserite, gypsum, and polyhydrated
      sulfates. This identification has its basis in vibrational absorptions between
      1.3 and 2.5 micrometers. These minerals constitute direct records of the past
      aqueous activity on Mars.

PMID- 15718431
TI  - Nurturing the next Einsteins.

PMID- 15718430
TI  - Mars surface diversity as revealed by the OMEGA/Mars Express observations.
AB  - The Observatoire pour la Mineralogie, l'Eau, les Glaces, et l'Activite (OMEGA)
      investigation, on board the European Space Agency Mars Express mission, is
      mapping the surface composition of Mars at a 0.3- to 5-kilometer resolution by
      means of visible-near-infrared hyperspectral reflectance imagery. The data
      acquired during the first 9 months of the mission already reveal a diverse and
      complex surface mineralogy, offering key insights into the evolution of Mars.
      OMEGA has identified and mapped mafic iron-bearing silicates of both the northern
      and southern crust, localized concentrations of hydrated phyllosilicates and
      sulfates but no carbonates, and ices and frosts with a water-ice composition of
      the north polar perennial cap, as for the south cap, covered by a thin carbon
      dioxide-ice veneer.

PMID- 15718432
TI  - High-energy physics. NSF stunned by higher costs of proposed DOE facility.

PMID- 15718433
TI  - NIH funding. Success rates squeezed as budget growth slows.

PMID- 15718434
TI  - U.S. immigration policy. New rules ease scientific exchanges.

PMID- 15718435
TI  - Planetary science. And now, the younger, dry side of Mars is coming out.

PMID- 15718436
TI  - Influenza. Study questions the benefits of vaccinating the elderly.

PMID- 15718438
TI  - Biomedical research. Despite protests, MRC to move its largest institute into
      London.

PMID- 15718437
TI  - Avian flu. First human case in Cambodia highlights surveillance shortcomings.

PMID- 15718439
TI  - Gene therapy. As Gelsinger case ends, gene therapy suffers another blow.

PMID- 15718440
TI  - German science. Board protest stops a shake-up of the Dahlem conferences.

PMID- 15718441
TI  - Biochemistry. Irresistible lure for cockroaches determined.

PMID- 15718442
TI  - Agricultural research. Ag schools say they can't afford budget boost.

PMID- 15718443
TI  - Environmental restoration. To save a vanishing sea.

PMID- 15718444
TI  - Environmental restoration. From samizdat to celebrity--and back.

PMID- 15718445
TI  - Wildlife biology. A devil of a disease.

PMID- 15718446
TI  - Taxonomy. Will DNA bar codes breathe life into classification?

PMID- 15718448
TI  - Taxonomy. Taxonomy's elusive grail.

PMID- 15718447
TI  - Taxonomy. Linnaeus's legacy carries on.

PMID- 15718450
TI  - Amazonian deforestation models.

PMID- 15718451
TI  - A delicate balance in Amazonia.

PMID- 15718449
TI  - Gender differences and performance in science.

PMID- 15718452
TI  - Underlying causes of deforestation.

PMID- 15718453
TI  - Medicine. Race and reification in science.

PMID- 15718454
TI  - Genetics. Harvesting medical information from the human family tree.

PMID- 15718455
TI  - Atmospheric science. Gamma rays made on Earth.

PMID- 15718456
TI  - Archaeology. Patterns of cultural primacy.

PMID- 15718457
TI  - Developmental biology. Life after deaf for hair cells?

PMID- 15718458
TI  - Ocean science. Ironing out biosphere oxidation.

PMID- 15718459
TI  - Neuroscience. Adaptive coding.

PMID- 15718460
TI  - Editing at the crossroad of innate and adaptive immunity.
AB  - Genetic information can be altered through the enzymatic modification of
      nucleotide sequences. This process, known as editing, was originally identified
      in the mitochondrial RNA of trypanosomes and later found to condition events as
      diverse as neurotransmission and lipid metabolism in mammals. Recent evidence
      reveals that editing enzymes may fulfill one of their most essential roles in the
      defense against infectious agents: first, as the mediators of antibody
      diversification, a step crucial for building adaptive immunity, and second, as
      potent intracellular poisons for the replication of viruses. Exciting questions
      are raised, which take us to the depth of the intimate relations between
      vertebrates and the microbial underworld.

PMID- 15718461
TI  - Entropically driven helix formation.
AB  - The helix is a ubiquitous motif for biopolymers. We propose a heuristic,
      entropically based model that predicts helix formation in a system of hard
      spheres and semiflexible tubes. We find that the entropy of the spheres is
      maximized when short stretches of the tube form a helix with a geometry close to
      that found in natural helices. Our model could be directly tested with wormlike
      micelles as the tubes, and the effect could be used to self-assemble
      supramolecular helices.

PMID- 15718462
TI  - Olmec pottery production and export in ancient Mexico determined through
      elemental analysis.
AB  - The first Mesoamerican civilization, the Gulf Coast Olmec, is associated with
      hierarchical society, monumental art, and an internally consistent ideology,
      expressed in a distinct style and salient iconography. Whether the Olmec style
      arose in just one area or emerged from interactions among scattered
      contemporaneous societies remains controversial. Using elemental analysis, we
      determined the regional clay sources of 725 archaeological ceramic samples from
      across Mesoamerica. Exported Olmec-style ceramics originated from the San Lorenzo
      region of the Gulf Coast, supporting Olmec priority in the creation and spread of
      the first unified style and iconographic system in Mesoamerica.

PMID- 15718463
TI  - Whole-genome patterns of common DNA variation in three human populations.
AB  - Individual differences in DNA sequence are the genetic basis of human
      variability. We have characterized whole-genome patterns of common human DNA
      variation by genotyping 1,586,383 single-nucleotide polymorphisms (SNPs) in 71
      Americans of European, African, and Asian ancestry. Our results indicate that
      these SNPs capture most common genetic variation as a result of linkage
      disequilibrium, the correlation among common SNP alleles. We observe a strong
      correlation between extended regions of linkage disequilibrium and functional
      genomic elements. Our data provide a tool for exploring many questions that
      remain regarding the causal role of common human DNA variation in complex human
      traits and for investigating the nature of genetic variation within and between
      human populations.

PMID- 15718464
TI  - Oxidative addition of ammonia to form a stable monomeric amido hydride complex.
AB  - The insertion of an iridium complex into an N-H bond in ammonia leads to a stable
      monomeric amido hydride complex in solution at room temperature. This reaction
      advances the transition-metal coordination chemistry of ammonia beyond its role
      for more than a century as an ancillary ligand. The precursor for this insertion
      reaction is an iridium(I) olefin complex with an aliphatic ligand containing one
      carbon and two phosphorus donor atoms. Kinetic and isotopic labeling studies
      indicate that olefin dissociates to give a 14-electron iridium(I) fragment, which
      then reacts with ammonia. This cleavage of the N-H bond under neutral conditions
      provides a foundation on which to develop future mild catalytic transformations
      of ammonia, such as olefin hydroamination and arene oxidative amination.

PMID- 15718465
TI  - Efficient bipedal robots based on passive-dynamic walkers.
AB  - Passive-dynamic walkers are simple mechanical devices, composed of solid parts
      connected by joints, that walk stably down a slope. They have no motors or
      controllers, yet can have remarkably humanlike motions. This suggests that these
      machines are useful models of human locomotion; however, they cannot walk on
      level ground. Here we present three robots based on passive-dynamics, with small
      active power sources substituted for gravity, which can walk on level ground.
      These robots use less control and less energy than other powered robots, yet walk
      more naturally, further suggesting the importance of passive-dynamics in human
      locomotion.

PMID- 15718466
TI  - Terrestrial gamma-ray flashes observed up to 20 MeV.
AB  - Terrestrial gamma-ray flashes (TGFs) from Earth's upper atmosphere have been
      detected with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI)
      satellite. The gamma-ray spectra typically extend up to 10 to 20 megaelectron
      volts (MeV); a simple bremsstrahlung model suggests that most of the electrons
      that produce the gamma rays have energies on the order of 20 to 40 MeV. RHESSI
      detects 10 to 20 TGFs per month, corresponding to approximately 50 per day
      globally, perhaps many more if they are beamed. Both the frequency of occurrence
      and maximum photon energy are more than an order of magnitude higher than
      previously known for these events.

PMID- 15718467
TI  - Iron isotope constraints on the Archean and Paleoproterozoic ocean redox state.
AB  - The response of the ocean redox state to the rise of atmospheric oxygen about 2.3
      billion years ago (Ga) is a matter of controversy. Here we provide iron isotope
      evidence that the change in the ocean iron cycle occurred at the same time as the
      change in the atmospheric redox state. Variable and negative iron isotope values
      in pyrites older than about 2.3 Ga suggest that an iron-rich global ocean was
      strongly affected by the deposition of iron oxides. Between 2.3 and 1.8 Ga,
      positive iron isotope values of pyrite likely reflect an increase in the
      precipitation of iron sulfides relative to iron oxides in a redox stratified
      ocean.

PMID- 15718468
TI  - Stem Lagomorpha and the antiquity of Glires.
AB  - We describe several fossils referable to Gomphos elkema from deposits close to
      the Paleocene-Eocene boundary at Tsagan Khushu, Mongolia. Gomphos shares a suite
      of cranioskeletal characters with extant rabbits, hares, and pikas but retains a
      primitive dentition and jaw compared to its modern relatives. Phylogenetic
      analysis supports the position of Gomphos as a stem lagomorph and excludes
      Cretaceous taxa from the crown radiation of placental mammals. Our results
      support the hypothesis that rodents and lagomorphs radiated during the Cenozoic
      and diverged from other placental mammals close to the Cretaceous-Tertiary
      boundary.

PMID- 15718469
TI  - Golgin tethers define subpopulations of COPI vesicles.
AB  - Coiled-coil proteins of the golgin family have been implicated in intra-Golgi
      transport through tethering coat protein complex I (COPI) vesicles. The p115
      golgin tether is the best studied, and here we characterize the golgin-84-CASP
      tether. The vesicles bound by this tether were strikingly different from those
      bound by the p115-golgin tether in that they lacked members of the p24 family of
      putative cargo receptors and contained enzymes instead of anterograde cargo.
      Microinjected golgin-84 or CASP also inhibited Golgi-enzyme transport to the
      endoplasmic reticulum, further implicating this tether in retrograde transport.
      These and other golgins may modulate the flow patterns within the Golgi stack.

PMID- 15718470
TI  - Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.
AB  - Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of
      cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr308 in
      the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser473
      within the carboxyl-terminal hydrophobic motif by an unknown kinase. We show that
      in Drosophila and human cells the target of rapamycin (TOR) kinase and its
      associated protein rictor are necessary for Ser473 phosphorylation and that a
      reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB
      effector. The rictor-mTOR complex directly phosphorylated Akt/PKB on Ser473 in
      vitro and facilitated Thr308 phosphorylation by PDK1. Rictor-mTOR may serve as a
      drug target in tumors that have lost the expression of PTEN, a tumor suppressor
      that opposes Akt/PKB activation.

PMID- 15718471
TI  - Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem
      cells.
AB  - Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers.
      However, the specific BCL-2 family member(s) that regulate HSC homeostasis are
      not precisely defined. We tested myeloid leukemia-1 (MCL-1) as an attractive
      candidate that is highly expressed in HSCs and regulated by growth factor
      signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow.
      This resulted in the loss of early bone marrow progenitor populations, including
      HSCs. Moreover, growth factors including stem cell factor increased transcription
      of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow
      progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair
      survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring
      the homeostasis of early hematopoietic progenitors.

PMID- 15718472
TI  - Identification of the sex pheromone of the German cockroach, Blattella germanica.
AB  - The sex pheromone of the German cockroach, Blattella germanica, has been
      characterized as gentisyl quinone isovalerate. This cockroach is a major cause of
      allergic disease and serves as a mechanical vector of pathogens, making it one of
      the most important residential and food-associated pests worldwide. The sex
      pheromone-producing gland in adult females was identified in 1993, but thermal
      instability of the pheromone made characterization difficult. Now, using a new
      preparative gas chromatography approach coupled with electroantennographic
      detection, we have isolated and characterized the pheromone, which we term
      blattellaquinone, and confirmed the identification by chemical synthesis. The
      synthetic pheromone was active in behavioral assays and highly effective in field
      trapping tests, which suggest that it may provide a new tool in cockroach
      population detection, monitoring, and control.

PMID- 15718473
TI  - Learned predictions of error likelihood in the anterior cingulate cortex.
AB  - The anterior cingulate cortex (ACC) and the related medial wall play a critical
      role in recruiting cognitive control. Although ACC exhibits selective error and
      conflict responses, it has been unclear how these develop and become context
      specific. With use of a modified stop-signal task, we show from integrated
      computational neural modeling and neuroimaging studies that ACC learns to predict
      error likelihood in a given context, even for trials in which there is no error
      or response conflict. These results support a more general error-likelihood
      theory of ACC function based on reinforcement learning, of which conflict and
      error detection are special cases.

PMID- 15718474
TI  - Flexible control of mutual inhibition: a neural model of two-interval
      discrimination.
AB  - Networks adapt to environmental demands by switching between distinct dynamical
      behaviors. The activity of frontal-lobe neurons during two-interval
      discrimination tasks is an example of these adaptable dynamics. Subjects first
      perceive a stimulus, then hold it in working memory, and finally make a decision
      by comparing it with a second stimulus. We present a simple mutual-inhibition
      network model that captures all three task phases within a single framework. The
      model integrates both working memory and decision making because its dynamical
      properties are easily controlled without changing its connectivity. Mutual
      inhibition between nonlinear units is a useful design motif for networks that
      must display multiple behaviors.

PMID- 15718476
TI  - Secondhand smoke, dietary fruit intake, road traffic exposures, and the
      prevalence of asthma: a cross-sectional study in young children.
AB  - The authors have investigated the independent effects of exposure to secondhand
      smoke, road vehicle traffic, and dietary fruit intake in a cross-sectional study
      of asthma in young children. They surveyed all children aged 4-6 years in 235
      schools in the East Midlands and East of England regions of the United Kingdom in
      2003. Data on respiratory symptoms, diagnoses and treatment, smoking in the home,
      and dietary fruit intake were collected by parental questionnaire. A geographic
      information system was used to map postcodes and determine the distance of the
      home from the nearest main road. Responses were obtained from 11,562 children.
      Wheeze in the past year and physician-diagnosed asthma were reported by 14.1% and
      18.2%, respectively. Both of these outcomes were more common in children who
      lived with a smoker, and the prevalence of asthma increased with the number of
      smokers in the home. Asthma prevalence was not associated with proximity of the
      home to a main road or with dietary fruit intake. The authors conclude that, of
      the potential risk factors considered in this study, preventing secondhand smoke
      exposure may be the most effective way of preventing asthma.

PMID- 15718478
TI  - Alcohol consumption, binge drinking, and early coronary calcification: findings
      from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
AB  - It is unclear to what extent the apparently beneficial cardiovascular effects of
      moderate alcohol consumption are mediated by protection against atherosclerosis.
      Alcohol consumption, coronary heart disease risk factors, and coronary
      calcification (a marker of atherosclerosis) were measured during 15 years of
      follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
      (1985-2001). Among 3,037 participants aged 33-45 years after follow-up (55%
      women, 45% Black), the prevalence of coronary calcification was 8% for
      consumption of 0 drinks/week (n = 1,435), 9% for 1-6 drinks/week (n = 1,023), 13%
      for 7-13 drinks/week (n = 341), and 19% for > or = 14 drinks/week (n = 238) (p <
      0.001 for trend). Calcification was also more common among binge drinkers (odds
      ratio = 2.1, 95% confidence interval: 1.6, 2.7). These associations persisted
      after adjustment for potential confounders (age, gender/ethnicity, income,
      physical activity, family history, body mass index, smoking) and intermediary
      factors (lipids, blood pressure, glucose, C-reactive protein, and fibrinogen).
      Stratification showed the dose-response relation most clearly in Black men; only
      heavier alcohol consumption (> or = 14 drinks/week) was associated with coronary
      calcification in other race/sex subgroups. These surprising findings suggest the
      presence of proatherogenic effects of alcohol in young adults, especially Black
      men, which may counterbalance high density lipoprotein cholesterol elevation and
      other possible benefits of alcohol consumption.

PMID- 15718477
TI  - Opposing effects of emphysema, hay fever, and select genetic variants on lung
      cancer risk.
AB  - The authors compared histories of nonmalignant respiratory diseases (asthma,
      bronchitis, emphysema, hay fever, and pneumonia) in 1,553 lung cancer patients
      and 1,375 healthy controls enrolled in a Texas case-control study from 1995 to
      2003. They incorporated data on two biologically relevant polymorphic genes,
      matrix metalloproteinase-1 and myeloperoxidase. Emphysema was associated with a
      statistically significant increased lung cancer risk (odds ratio (OR) = 2.87, 95%
      confidence interval (CI): 2.20, 3.76), while hay fever had a significant
      protective effect (OR = 0.58, 95% CI: 0.48, 0.70). Odds ratios were consistent
      after exclusion of respiratory disease diagnoses made up to 10 years before
      interview. There was little association between other respiratory diseases and
      lung cancer risk. Among carriers of "protective" genotypes, emphysema was
      associated with a 1.7-fold increased risk (95% CI: 0.84, 3.50), as compared with
      the substantially higher risk for persons possessing one (OR = 4.98, 95% CI:
      2.94, 8.44) or two (OR = 4.23, 95% CI: 1.84, 9.73) "adverse" genotypes. For hay
      fever, significantly decreased risks were evident with one (OR = 0.32, 95% CI:
      0.21, 0.50) or two (OR = 0.35, 95% CI: 0.19, 0.66) protective genotypes as
      compared with none (OR = 0.69, 95% CI: 0.30, 1.59). The biologic role of
      respiratory disease in lung cancer is unclear. Further study may yield new
      insights for identification of susceptible subgroups.

PMID- 15718479
TI  - Perceived job stress and incidence of coronary events: 3-year follow-up of the
      Belgian Job Stress Project cohort.
AB  - Psychosocial characteristics have been linked to coronary heart disease. In the
      Belgian Job Stress Project (1994-1999), the authors examined the independent role
      of perceived job stress on the short-term incidence of clinical manifest coronary
      events in a large occupational cohort. A total of 14,337 middle-aged men
      completed the Job Content Questionnaire to determine the dimensions of the
      extended job strain model, job demands, decision latitude, and social support.
      Jobs were categorized into high strain, low strain, active jobs, and passive
      jobs. During the 3-year follow-up, 87 coronary events were registered. At
      baseline, 17% of workers experienced high strain. Job demands and decision
      latitude were not significantly related to the development of coronary heart
      disease after adjustment for covariates. The 38% risk excess among subjects
      classified in the high-strain category did not reach statistical significance.
      However, coronary heart disease incidence was substantially associated with the
      social support scale independently of other risk factors, with an adjusted hazard
      ratio of 2.4 (95% confidence interval: 1.4, 4.0) between extreme tertiles. No
      convincing evidence for an association of job demands, decision latitude, or job
      strain with the short-term incidence of coronary heart disease was found.
      However, our study underscores the importance of a supportive social work
      environment in the prevention of coronary heart disease.

PMID- 15718480
TI  - Genetic variation in the progesterone receptor gene and ovarian cancer risk.
AB  - Evidence suggests a role for progesterone in ovarian cancer development.
      Progesterone exerts its effect on target cells by interacting with its receptor.
      Thus, genetic variations that may cause alterations in the biologic functions of
      the progesterone receptor can potentially contribute to individual susceptibility
      to ovarian cancer. Using a population-based, case-control study, the authors
      genotyped four polymorphisms in the progesterone receptor gene (+44C/T, +331G/A,
      G393G, V660L) and inferred haplotypes in 987 ovarian cancer cases and 1,034
      controls living in New Hampshire and eastern Massachusetts (May 1992-November
      2002). Odds ratios and 95% confidence intervals were calculated to evaluate
      associations with ovarian cancer. No associations were observed between the
      +44C/T, +331G/A, and G393G polymorphisms and ovarian cancer. However, an inverse
      association was observed between the V660L variant and ovarian cancer (odds ratio
      = 0.70, 95% confidence interval: 0.57, 0.85). Associations remained after
      adjustment for potential confounders. Five haplotypes occurred with greater than
      5% frequency, and the haplotype carrying the V660L variant had a significant
      association with ovarian cancer (odds ratio = 0.76, 95% confidence interval:
      0.62, 0.92). Associations were similar after stratifying by ovarian cancer
      histologies and risk factors.

PMID- 15718481
TI  - Relations of gestational length and timing and type of incomplete pregnancy to
      ovarian cancer risk.
AB  - While the protective nature of parity with respect to ovarian cancer has been
      well documented, whether a history of incomplete pregnancy affects ovarian cancer
      risk is uncertain. Data collected from 739 epithelial ovarian cancer cases and
      1,313 community controls in the Delaware Valley from 1994 to 1998 were used to
      evaluate the relation between gestational length and timing of first induced or
      spontaneous abortion and ovarian cancer risk. Incomplete pregnancy was not
      associated with ovarian cancer among nulliparous women or among ever-pregnant
      women either before or after adjustment for relevant confounders (for nulliparous
      women, odds ratio (OR) = 1.12, 95% confidence interval (CI): 0.66, 1.89; for ever
      pregnant women, OR = 0.95, 95% CI: 0.76, 1.18). Among unigravid women, one full
      term pregnancy was more protective than an incomplete pregnancy (adjusted OR =
      0.29, 95% CI: 0.15, 0.57). These results were independent of the type of
      pregnancy loss. Among ever-pregnant women, a spontaneous abortion before a first
      birth provided significant protection (adjusted OR = 0.47, 95% CI: 0.30, 0.75),
      while no significant effect was found for an induced abortion prior to a first
      birth (adjusted OR = 0.80, 95% CI: 0.44, 1.47). These data do not support an
      independent association between incomplete pregnancies, either spontaneous or
      induced, and ovarian cancer risk.

PMID- 15718482
TI  - Serum levels of polyunsaturated fatty acids and risk of colorectal cancer: a
      prospective study.
AB  - To examine the relation between serum fatty acids and risk of colorectal cancer,
      the authors conducted a nested case-control study of 169 colorectal cancer cases
      and 481 controls matched by age and enrollment area as part of the Japan
      Collaborative Cohort Study. Serum samples were donated by subjects at baseline
      (between 1988 and 1990) and were stored at -80 degrees C until 2002. Serum fatty
      acid levels were measured by using gas chromatography and were expressed as the
      weight percentage of total lipids. Conditional logistic regression analyses
      adjusted for lifestyle factors revealed that total omega-3 polyunsaturated fatty
      acids (odds ratio = 0.24, 95% confidence interval: 0.08, 0.76), alpha-linolenic
      acid (odds ratio = 0.39, 95% confidence interval: 0.16, 0.91), docosapentaenoic
      acid (odds ratio = 0.30, 95% confidence interval: 0.11, 0.80), and
      docosahexaenoic acid (odds ratio = 0.23, 95% confidence interval: 0.07, 0.76) all
      showed a significantly decreased risk for the highest versus the lowest quartile
      levels for colorectal cancer in men. For women, a weak negative association was
      observed between docosapentaenoic acid and colorectal cancer risk, although it
      was not statistically significant. No adverse effects of high serum levels of
      omega-6 polyunsaturated fatty acids on colorectal cancer risk were detected.

PMID- 15718483
TI  - A randomized, controlled trial of in-home drinking water intervention to reduce
      gastrointestinal illness.
AB  - Trials have provided conflicting estimates of the risk of gastrointestinal
      illness attributable to tap water. To estimate this risk in an Iowa community
      with a well-run water utility with microbiologically challenged source water, the
      authors of this 2000-2002 study randomly assigned blinded volunteers to use
      externally identical devices (active device: 227 households with 646 persons;
      sham device: 229 households with 650 persons) for 6 months (cycle A). Each group
      then switched to the opposite device for 6 months (cycle B). The active device
      contained a 1-microm absolute ceramic filter and used ultraviolet light. Episodes
      of "highly credible gastrointestinal illness," a published measure of diarrhea,
      nausea, vomiting, and abdominal cramps, were recorded. Water usage was recorded
      with personal diaries and an electronic totalizer. The numbers of episodes in
      cycle A among the active and sham device groups were 707 and 672, respectively;
      in cycle B, the numbers of episodes were 516 and 476, respectively. In a log
      linear generalized estimating equations model using intention-to-treat analysis,
      the relative rate of highly credible gastrointestinal illness (sham vs. active)
      for the entire trial was 0.98 (95% confidence interval: 0.86, 1.10). No reduction
      in gastrointestinal illness was detected after in-home use of a device designed
      to be highly effective in removing microorganisms from water.

PMID- 15718484
TI  - Utility of the Chronic Disease Score and Charlson Comorbidity Index as
      comorbidity measures for use in epidemiologic studies of antibiotic-resistant
      organisms.
AB  - Comorbidity is a known risk factor for antibiotic-resistant bacterial infections.
      Although aggregate comorbidity measures are useful in epidemiologic research,
      none of the existing measures was developed for use with this outcome. This study
      compared the utility of two comorbidity measures, the Charlson Comorbidity Index
      and the Chronic Disease Score, in assessing the comorbidity-attributable risk of
      nosocomial infections with methicillin-resistant Staphylococcus aureus (MRSA) or
      vancomycin-resistant enterococci (VRE). Two case-control studies were conducted
      at the University of Maryland Medical System in Baltimore, Maryland. Cases were
      inpatients with a first positive clinical culture of MRSA or VRE at least 48
      hours postadmission (July 1, 1998-July 1, 2001). Three inpatient controls were
      randomly selected per case. The MRSA study included 2,164 patients, and the VRE
      study included 1,948. The scores' discrimination and calibration were measured by
      using the c statistic and Hosmer-Lemeshow chi-square test. The Charlson
      Comorbidity Index (c = 0.653) and Chronic Disease Score (c = 0.608) were similar
      discriminators of MRSA and VRE (c = 0.670 and c = 0.647, respectively).
      Calibration of the scores was poor for both outcomes (p < 0.05). A revised
      comorbidity measure specific to resistant infections would likely provide a
      better assessment of the comorbidity-attributable risk of antibiotic-resistant
      infections.

PMID- 15718485
TI  - An analysis of American Journal of Epidemiology citations with special reference
      to statistics and social science.
AB  - In an effort to inform the ongoing discussion about the purpose, purview,
      theoretical orientation, and viability of epidemiology, this paper considers the
      contemporary epistemological foundations of the discipline by analyzing article
      citations. Two principal questions are the following: 1) What research do
      American Journal of Epidemiology (AJE) authors rely on to support, inform, and
      frame their investigations? and 2) to what extent do such authors use social
      scientific and statistical citations? The data used appear to be superior to
      those used in previous efforts because they contain complete citations for all
      articles published, along with complete within-article citations, for all AJE
      articles published from January 1981 to December 2002. The most frequent AJE
      citations are statistically oriented works. About 9% of citations are to AJE
      articles, 15% are to a larger set of eight epidemiologic journals, 15% are to a
      select set of eight medical journals, 3% are to (bio)statistics journals, and
      just 0.2% are to social science journals. Trend analysis reveals little change
      during the 22-year study period. The principal implication is that AJE authors
      are overlooking a vast literature that could inform their understanding of how
      exposures emerge and are maintained.

PMID- 15718486
TI  - Use of an in vivo biotinylated single-chain antibody as capture reagent in an
      immunometric assay to decrease the incidence of interference from heterophilic
      antibodies.
AB  - BACKGROUND: Heterophilic antibodies are a common source of interference in
      immunometric assays. We tested the hypothesis that the incidence of such
      interference could be decreased by use of a recombinant in vivo-biotinylated
      single-chain antibody (scFv) as the capture reagent. METHODS: We established
      three assays for carcinoembryonic antigen (CEA) with the capture antibody either
      chemically biotinylated whole monoclonal T84.66 immunoglobulin, a corresponding
      F(ab')2 fragment, or a site-specifically biotinylated T84.66-derived single-chain
      antibody (scFv). Antibodies were attached to streptavidin-coated microplates. A
      common europium-labeled anti-CEA tracer monoclonal antibody was used. The F(ab')2
      assay used a buffer that contained bovine immunoglobulin and aggregated
      irrelevant monoclonal antibody MAK33 as blocking agents. The whole T84.66
      immunoglobulin and scFv assays were performed without addition of blocking
      agents. From a previous study of 11 261 sera, we tested 390 samples that had
      displayed heterophilic antibody interference and 179 samples that had not.
      RESULTS: After correction for bias and analytical variation [2.56 x SD (from the
      precision profile)], 383 samples displayed significantly different values (>1
      microg/L) in the whole T84.66-based assay and the F(ab')2 assay. In contrast,
      only nine samples showed falsely high CEA concentrations in the scFv assay. After
      blocking agents were added to the assay buffer, eight of the nine samples
      displayed results equivalent to those of the F(ab')2 assay, and sample dilution
      produced equivalent results for the remaining sample. CONCLUSION: Their ability
      to be site-specifically biotinylated and their relative resistance to
      heterophilic antibody interference indicate that single-chain antibodies may be
      useful solid-phase reagents in immunometric assays.

PMID- 15718487
TI  - Pheochromocytoma catecholamine phenotypes and prediction of tumor size and
      location by use of plasma free metanephrines.
AB  - BACKGROUND: Measurements of plasma free metanephrines (normetanephrine and
      metanephrine) provide a useful test for diagnosis of pheochromocytoma and may
      provide other information about the nature of these tumors. METHODS: We examined
      relationships of tumor size, location, and catecholamine content with plasma and
      urinary metanephrines or catecholamines in 275 patients with pheochromocytoma. We
      then prospectively examined whether measurements of plasma free metanephrines
      could predict tumor size and location in an additional 16 patients. RESULTS:
      Relative proportions of epinephrine and norepinephrine in tumor tissue were
      closely matched by relative increases of plasma or urinary metanephrine and
      normetanephrine, but not by epinephrine and norepinephrine. Tumor diameter showed
      strong positive relationships with summed plasma concentrations or urinary
      outputs of metanephrine and normetanephrine (r = 0.81 and 0.77; P <0.001),
      whereas relationships with plasma or urinary catecholamines were weaker (r = 0.41
      and 0.44). All tumors in which increases in plasma metanephrine were >15% of the
      combined increases of normetanephrine and metanephrine either had adrenal
      locations or appeared to be recurrences of previously resected adrenal tumors.
      Measurements of plasma free metanephrines predicted tumor diameter to within a
      mean of 30% of actual diameter, and high plasma concentrations of free
      metanephrine relative to normetanephrine accurately predicted adrenal locations.
      CONCLUSIONS: Measurements of plasma free metanephrines not only provide
      information about the likely presence or absence of a pheochromocytoma, but when
      a tumor is present, can also help predict tumor size and location. This
      additional information may be useful for clinical decision-making during tumor
      localization procedures.

PMID- 15718488
TI  - Comparison of cardiac troponin I immunoassays variably affected by circulating
      autoantibodies.
AB  - BACKGROUND: We recently provided evidence that circulating autoantibodies against
      cardiac troponin I (cTnI) or the troponin complex cause negative interference in
      cTnI immunoassays. By comparing three cTnI immunoassays, we further explored the
      phenomenon of circulating autoantibodies and their consequences in patient
      samples. METHODS: We developed a cTnI immunoassay with a novel assay design using
      three antibodies, two of which bind epitopes outside the stable, central part of
      cTnI. Samples from 541 chest pain patients were measured with the new cTnI assay
      and with a first-generation cTnI assay (Innotrac Aio cTnI) using a conventional
      midfragment assay design. Using another sample cohort, we also compared the new
      assay with a second-generation cTnI assay (Access AccuTnI). RESULTS: The
      analytical detection limit of the new cTnI assay was 0.012 microg/L, and the
      lowest concentration giving a total imprecision (CV) of 10% was 0.060 microg/L.
      The mean difference (95% limits of agreement) between the new cTnI and Aio cTnI
      assays was larger in admission samples (21.0%; -107.8% to 149.7%) than in samples
      taken 6-12 h (12.8%; -61.5% to 87.2%) and 24 h after admission (3.0%; -71.3% to
      77.4%; P <0.001). With the lowest concentrations giving 10% CV (0.22 microg/L for
      Aio cTnI) used as cutoffs, 14.3% (n = 76) of admission samples were positive only
      with the new assay, whereas 13.5% (n = 72) were positive with both assays. Of
      samples taken at 6-12 and 24 h, 10.2% (n = 31) and 8.3% (n = 29) were positive
      only with the new assay. ROC curve analysis of admission samples showed a
      significantly higher area under the curve for the new cTnI assay (0.940) than for
      the Aio cTnI assay (0.846; P <0.001). The new cTnI assay gave generally lower
      results than the AccuTnI assay; the mean (95% limits of agreement) differences
      were -58.9% (-151.8% to 34.0%) in admission samples. In samples with severe
      interference from autoantibodies, median ratios between the new assay and AccuTnI
      were higher than in samples with no apparent troponin autoantibodies (0.875 vs
      0.481; P<0.001). CONCLUSIONS: The new cTnI assay, which is based on a novel
      antibody combination different from the conventional midfragment antibody
      approach, offers improved detection of cTnI in samples containing troponin
      autoantibodies.

PMID- 15718489
TI  - Negative interference in cardiac troponin I immunoassays by circulating troponin
      autoantibodies.
AB  - BACKGROUND: There are numerous potential sources of interference in immunoassays.
      Our aim was to identify the blood component that causes negative interference in
      cardiac troponin I (cTnI) immunoassays based on antibodies against the central
      part of cTnI. METHODS: We isolated an interfering factor (IF) from a sample with
      low recovery of added cTnI, using several consecutive purification steps:
      caprylic acid precipitation, ammonium sulfate precipitation, and purification on
      Cibacron Blue gel and protein G columns. Purified IF was identified by gel
      electrophoresis and mass spectrometric analysis of protein bands. For the direct
      detection of human antibodies to cardiac troponin in serum samples, we developed
      immunoassays using three different anti-human immunoglobulin antibodies and
      measured troponin antibodies in samples with low and normal cTnI recovery.
      RESULTS: Treatment with caprylic acid did not precipitate IF, but IF precipitated
      at 40% ammonium sulfate saturation. IF bound to a Cibacron Blue gel column, from
      which it was eluted with a linear salt gradient; it also bound to protein G. Gel
      electrophoresis of purified IF showed two major bands with molecular masses
      corresponding to the heavy (approximately 50 kDa) and light chains (approximately
      25 kDa) of immunoglobulin, and their identities were confirmed by mass
      spectrometry. The presence of troponin-specific autoantibodies was confirmed in
      samples with low recoveries of cTnI by three different immunoassays. The median
      signals were significantly higher in 10 samples with low recovery than in 10
      samples with normal recovery of cTnI (P < or = 0.007). CONCLUSIONS: Circulating
      autoantibodies to cTnI or other proteins of the troponin complex can be a source
      of negative interference in cTnI immunoassays.

PMID- 15718490
TI  - Single assay for amino-terminal fragments of cardiac A- and B-type natriuretic
      peptides.
AB  - BACKGROUND: High circulating concentrations of N-terminal fragments of A- and B
      type natriuretic peptides (NT-proANP and NT-proBNP) identify patients with
      impaired cardiac function. ProANP-derived peptides are particularly sensitive to
      increased preload of the heart and proBNP-derived peptides to increased
      afterload; therefore, combining the information from the ANP and BNP systems into
      a single analyte could produce an assay with increased diagnostic and prognostic
      power. METHODS: We prepared a hybrid peptide containing peptide sequences from
      both NT-proBNP and NT-proANP (referred to as NT-proXNP) by recombinant techniques
      and used it to develop a RIA combining weighed concentrations of NT-proANP and NT
      proBNP into a new virtual analyte, NT-proXNP. We used the novel method to measure
      the circulating concentrations in healthy persons and in patients with cardiac
      disorders. We also characterized the assay by HPLC analysis of the immunoreactive
      molecular forms in human plasma and serum. RESULTS: The results from the novel
      assay correlated well with independent home-made NT-proANP and NT-proBNP assays
      (r2 = 0.75-0.85) as well with the arithmetic sum of NT-proANP and NT-proBNP (r2 =
      0.92). Patients with valvular heart disease (VHD) and coronary artery disease
      (CAD) had significantly increased NT-proXNP concentrations. The areas under the
      curve (AUC) of the NT-proXNP assay in detecting VHD and CAD (0.961 and 0.924,
      respectively) were significantly larger than the AUC of either NT-proANP (0.947
      and 0.872) or NT-proBNP (0.913 and 0.782) assays. HPLC analysis showed that the
      novel NT-proXNP assay detects two major classes of circulating immunoreactivity
      corresponding to peptides derived from NT-proANP and NT-proBNP. CONCLUSIONS: Our
      novel immunoassay mimics the physiologic signaling system working in the body by
      converging the information obtained from the activation of ANP and BNP into a
      single virtual analyte, NT-proXNP. It appears to have a diagnostic efficiency
      equal to or slightly better than that of individual NT-proANP or NT-proBNP
      assays.

PMID- 15718491
TI  - C-reactive protein inhibits endothelium-dependent NO-mediated dilation in
      coronary arterioles by activating p38 kinase and NAD(P)H oxidase.
AB  - OBJECTIVE: Elevated levels of C-reactive protein (CRP), a proinflammatory marker,
      are associated with reduced systemic endothelium-dependent NO-mediated dilation
      in patients with coronary artery disease; however, the direct effect of CRP on
      coronary microvascular reactivity remains unknown. Herein, we examined whether
      CRP can modulate endothelium-dependent NO-mediated dilation of coronary
      arterioles and whether proinflammatory signaling pathways such as stress
      activated protein kinases (p38 and c-Jun N-terminal kinase [JNK]) and oxidative
      stress are involved in the CRP-mediated effect. METHODS AND RESULTS: Porcine
      coronary arterioles were isolated and pressurized without flow for in vitro
      study. Intraluminal treatment with a clinically relevant concentration of CRP (7
      microg/mL; 1 hour) significantly attenuated the NO release and vasodilation to
      serotonin. Further incubation with the NO precursor l-arginine (3 mmol/L)
      partially restored serotonin-induced vasodilation. In the presence of superoxide
      scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), NAD(P)H
      oxidase inhibitor apocynin, or p38 kinase (an upstream activator of NAD(P)H
      oxidase) inhibitor SB203850, but not xanthine oxidase inhibitor allopurinol or
      JNK inhibitor SP600125, the detrimental effect of CRP on serotonin-induced
      dilation was prevented. Dihydroethidium staining showed that CRP produced
      SB203850- and TEMPOL-sensitive superoxide production in the arteriolar
      endothelium. CRP treatment of coronary arterioles significantly increased NAD(P)H
      oxidase activity. CONCLUSIONS: CRP inhibits endothelium-dependent NO-mediated
      dilation in coronary arterioles by producing superoxide from NAD(P)H oxidase via
      p38 kinase activation. By impairing endothelium-dependent NO-mediated
      vasoreactivity, CRP could facilitate the initiation of numerous cardiovascular
      diseases.

PMID- 15718492
TI  - Shear stress inhibits smooth muscle cell-induced inflammatory gene expression in
      endothelial cells: role of NF-kappaB.
AB  - OBJECTIVES: Vascular endothelial cells (ECs) are influenced by shear stress and
      neighboring smooth muscle cells (SMCs). We investigated the inflammation-relevant
      gene expression in EC/SMC cocultures under static condition and in response to
      shear stress. MATERIALS AND METHODS: Under static condition, DNA microarrays and
      reverse-transcription polymerase chain reaction identified 23 inflammation
      relevant genes in ECs whose expression was significantly affected by coculture
      with SMCs, with 18 upregulated and 5 downregulated. Application of shear stress
      (12 dynes/cm2) to the EC side of the coculture for 6 hours inhibited most of the
      proinflammatory gene expressions in ECs induced by coculture with SMCs.
      Inhibition of nuclear factor-kappaB (NF-kappaB) activation by the p65-antisense,
      lactacystin, and N-acetyl-cysteine blocked the coculture-induced EC expression of
      proinflammatory genes, indicating that the NF-kappaB binding sites in the
      promoters of these genes play a significant role in their expression as a result
      of coculture with SMCs. Chromatin immunoprecipitation assays demonstrated the in
      vivo regulation of NF-kappaB recruitment to selected target promoters. Shear
      stress inhibited the SMC coculture-induced NF-kappaB activation in ECs and
      monocytic THP-1 cell adhesion to ECs. CONCLUSIONS: Our findings suggest that
      shear stress plays an inhibitory role in the proinflammatory gene expression in
      ECs located in close proximity to SMCs.

PMID- 15718493
TI  - Toll-like receptor 4-dependent and -independent cytokine secretion induced by
      minimally oxidized low-density lipoprotein in macrophages.
AB  - OBJECTIVE: Innate immune responses to oxidized low-density lipoprotein LDL (LDL)
      regulate the development of atherosclerosis. We demonstrated previously that an
      early form of oxidized LDL, minimally modified LDL (mmLDL), triggers cytoskeletal
      rearrangements in macrophages via CD14 and Toll-like receptor 4 (TLR4)/MD-2.
      Because lipopolysaccharide (LPS) activation of TLR4 leads to proinflammatory gene
      expression, in this study, we asked whether mmLDL also induced proinflammatory
      signaling. METHODS AND RESULTS: We studied cytokine secretion and signaling in
      J774 and primary peritoneal macrophages stimulated with mmLDL, which was prepared
      by incubating LDL with cells expressing human 15-lipoxygenase. MmLDL stimulated
      robust phosphoinositide 3-kinase (PI3K) activation, and Akt and extracellular
      signal-regulated kinase 1/2 (ERK1/2) phosphorylation, which exceeded that induced
      by LPS. On the other hand, although mmLDL induced nuclear factor kappaB (NF
      kappaB) p65 translocation to the nucleus, there was no detectable NF-kappaB
      activation. However, mmLDL induced early mRNA and protein expression of the
      cytokines MIP-2, MCP-1, tumor necrosis factor-alpha, and interleukin-6. Chemokine
      MIP-2 but not MCP-1 secretion depended on TLR4/MyD88, ERK1/2, and PI3K signaling.
      In turn, TLR4 regulated phosphorylation of ERK1/2 but not of Akt, suggesting that
      mmLDL-induced PI3K activation is TLR4 independent. CONCLUSIONS: In macrophages,
      mmLDL activates TLR4-dependent and -independent signaling pathways, resulting in
      secretion of proinflammatory cytokines. These results provide new insights into
      the inflammatory origins of atherosclerosis.

PMID- 15718494
TI  - Activator protein-1 mediates shear stress-induced prostaglandin d synthase gene
      expression in vascular endothelial cells.
AB  - OBJECTIVE: We attempted to determine the molecular mechanism of fluid shear
      stress-induced lipocalin-type prostaglandin D synthase (l-PGDS) expression in
      vascular endothelial cells. METHODS AND RESULTS: We examined the promoter region
      of the l-PGDS gene by loading laminar shear stress (20 dyne/cm2), using a
      parallel-plate flow chamber, on endothelial cells transfected with luciferase
      reporter vectors containing the 5'-flanking regions of the human l-PGDS gene. A
      deletion mutant analysis revealed that a shear stress-responsive element resided
      in the region between -2607 and -2523 bp. A mutation introduced into the putative
      binding site for activator protein-1 (AP-1) within this region eliminated the
      response to shear stress. In an electrophoretic mobility shift assay, shear
      stress stimulated nuclear protein binding to the AP-1 binding site, which was
      supershifted by antibodies to c-Fos and c-Jun. Shear stress elevated the c-Jun
      phosphorylation level in a time-dependent manner, similar to that of l-PGDS gene
      expression. SP600125, a c-Jun N-terminal kinase inhibitor, decreased the c-Jun
      phosphorylation, DNA binding of AP-1, and l-PGDS expression induced by shear
      stress. Additionally, an mRNA chase experiment using actinomycin D demonstrated
      that shear stress did not stabilize l-PGDS mRNA. CONCLUSIONS: Shear stress
      induces l-PGDS expression by transcriptional activation through the AP-1 binding
      site.

PMID- 15718495
TI  - Interleukin-6 and mevastatin regulate plasminogen activator inhibitor-1 through
      CCAAT/enhancer-binding protein-delta.
AB  - OBJECTIVE: We sought to determine the etiologic mechanism of proinflammatory
      cytokine, interleukin-6 (IL-6), and statin as regulators of synthesis of
      plasminogen activator inhibitor-1 (PAI-1), the physiological fibrinolysis
      inhibitor and an acute-phase reactant. METHODS AND RESULTS: Transient
      transfection and luciferase assay in HepG2 human hepatoma-derived cells
      demonstrated that IL-6 increased PAI-1 promoter activity and mevastatin decreased
      IL-6-inducible response. Systematic deletion assay of the promoter demonstrated
      that the region (-239 to -210 bp) containing a putative CCAAT/enhancer-binding
      protein (C/EBP) binding site was necessary. Point mutation in this site abolished
      the IL-6-inducible response. Electrophoretic mobility shift assay and chromatin
      immunoprecipitation assay demonstrated that C/EBPalpha, C/EBPbeta, and C/EBPdelta
      were involved in protein-DNA complex formation in intact cells. Deoxyribonuclease
      (DNase) I footprinting analysis revealed that 5' flanking region (-232 to -210
      bp) is acute-phase response protein-binding site. C/EBPdelta binding activity was
      increased by IL-6 and attenuated by mevastatin. Mevastatin attenuated IL-6
      mediated increase of C/EBPdelta protein in the nuclear extracts. IL-6 also
      increased PAI-1 and C/EBPdelta mRNA in mouse primary hepatocytes. CONCLUSIONS: IL
      6 increases hepatic PAI-1 expression mediated by the -232- to -210-bp region of
      the promoter containing a C/EBPdelta binding site. Vascular protection by statins
      may be partly mediated through regulation of CEBPdelta and consequent modulation
      of PAI-1 expression.

PMID- 15718496
TI  - Role of caspases in death and survival of the plaque macrophage.
AB  - This review considers the role of macrophage cell death in formation of the
      necrotic core and in plaque progression, and lists many of the possible mediators
      of macrophage cell death. Among these, perhaps the most cited toxic agent is
      oxidized low-density lipoprotein (oxLDL). Whereas oxLDL can kill macrophage, and
      whereas the form of death is morphologically apoptotic, caspase inhibitors appear
      to be ineffective in preventing death. This finding is consistent with recent
      literature showing how the canonical caspase pathways are used for physiological
      cellular functions other than cell death. Plaque macrophages appear to be among
      the cells with this nonapoptotic signaling function for activated caspases. In
      many of the other cell types, caspase activation appears to play a critical role
      in cell differentiation. We discuss possible functions of plaque macrophage using
      the nondeath caspase pathway. Recent literature shows that physiological and
      developmental functions of many cell types require active caspases without
      progressing to cell death. We discuss the role of macrophage cell death in plaque
      progression, possible mediators of macrophage cell death, and the possible
      functions of plaque macrophage using the nondeath caspase pathway.

PMID- 15718497
TI  - Angiotensin II and aldosterone regulate gene transcription via functional
      mineralocortocoid receptors in human coronary artery smooth muscle cells.
AB  - Inhibition or blockade of the angiotensin-aldosterone system consistently
      decreases ischemic cardiovascular events in clinical trials. The steroid hormone
      aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand
      activated transcription factor that is a member of the nuclear hormone receptor
      superfamily. MR binds and is activated by aldosterone and cortisol with equal
      affinity, but MR activation by cortisol is diminished in tissues that express the
      cortisol-inactivating enzyme 11-beta-hydroxysteroid-dehydrogenase-2 (11betaHSD2).
      Although previous studies support that the vasculature is a target tissue of
      aldosterone, MR-mediated gene expression in vascular cells has not been
      demonstrated or systematically explored. We investigated whether functional MR
      and 11betaHSD2 are expressed in human blood vessels. Human coronary and aortic
      vascular smooth muscle cells (VSMCs) express mRNA and protein for both MR and
      11betaHSD2. The endogenous VSMC MR mediates aldosterone-dependent gene
      expression, which is blocked by the competitive MR antagonist spironolactone.
      Inhibition of 11betaHSD2 in coronary artery VSMCs enhances gene transactivation
      by cortisol, supporting that the VSMC 11betaHSD2 is functional. Angiotensin II
      also activates MR-mediated gene transcription in coronary artery VSMCs.
      Angiotensin II activation of MR-mediated gene expression is inhibited by both the
      AT1 receptor blocker losartan and by spironolactone, but not by aldosterone
      synthase inhibition. Microarray and quantitative RT-PCR experiments show that
      aldosterone activates expression of endogenous human coronary VSMC genes,
      including several involved in vascular fibrosis, inflammation, and calcification.
      These data support a new MR-dependent mechanism by which aldosterone and
      angiotensin II influence ischemic cardiovascular events, and suggest that ACE
      inhibitors and MR antagonists may decrease clinical ischemic events by inhibiting
      MR-dependent gene expression in vascular cells.

PMID- 15718498
TI  - Kruppel-like factor 2 (KLF2) regulates endothelial thrombotic function.
AB  - The vascular endothelium maintains blood fluidity by inhibiting blood
      coagulation, inhibiting platelet aggregation, and promoting fibrinolysis.
      Endothelial cells lose these nonthrombogenic properties on exposure to
      proinflammatory stimuli. We recently identified the Kruppel-like factor KLF2 as a
      novel regulator of endothelial proinflammatory activation. Here it is found that
      KLF2 differentially regulates key factors involved in maintaining an
      antithrombotic endothelial surface. Overexpression of KLF2 strongly induced
      thrombomodulin (TM) and endothelial nitric oxide synthase (eNOS) expression and
      reduced plasminogen activator inhibitor-1 (PAI-1) expression. Furthermore,
      overexpression of KLF2 inhibited the cytokine-mediated induction of tissue factor
      (TF). In contrast, siRNA mediated knockdown of KLF2 reduced antithrombotic gene
      expression while inducing the expression of pro-coagulant factors. The functional
      importance of KLF2 was verified by in vitro clotting assays. By comparison to
      control infected cells, KLF2 overexpression increased blood clotting time as well
      as flow rates under basal and inflammatory conditions. In contrast, siRNA
      mediated knockdown of KLF2 reduced blood clotting time and flow rates. These
      observations identify KLF2 as a novel transcriptional regulator of endothelial
      thrombotic function. The full text of this article is available online at
      http://circres.ahajournals.org.

PMID- 15718499
TI  - Divergent siblings: E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in
      cardiomyocytes without activation of apoptosis.
AB  - Proliferation of mammalian cardiomyocytes ceases around birth when a transition
      from hyperplastic to hypertrophic myocardial growth occurs. Previous studies
      demonstrated that directed expression of the transcription factor E2F1 induces S
      phase entry in cardiomyocytes along with stimulation of programmed cell death.
      Here, we show that directed expression of E2F2 and E2F4 by adenovirus mediated
      gene transfer in neonatal cardiomyocytes induced S-phase entry but did not result
      in an onset of apoptosis whereas directed expression of E2F1 and E2F3 strongly
      evoked programmed cell death concomitant with cell cycle progression. Although
      both E2F2 and E2F4 induced S-phase entry only directed expression of E2F2
      resulted in mitotic cell division of cardiomyocytes. Expression of E2F5 or a
      control LacZ-Adenovirus had no effects on cell cycle progression. Quantitative
      real time PCR revealed that E2F1, E2F2, E2F3, and E2F4 alleviate G0 arrest by
      induction of cyclinA and E cyclins. Furthermore, directed expression of E2F1,
      E2F3, and E2F5 led to a transcriptional activation of several proapoptotic genes,
      which were mitigated by E2F2 and E2F4. Our finding that expression of E2F2
      induces cell division of cardiomyocytes along with a suppression of proapoptotic
      genes might open a new access to improve the regenerative capacity of
      cardiomyocytes.

PMID- 15718500
TI  - Impairment in postischemic neovascularization in mice lacking the CXC chemokine
      receptor 3.
AB  - Inflammatory cell infiltration is a feature of postischemic neovascularization.
      However, mechanisms leading to leukocyte attraction to the site of
      neovascularization are still undefined. We hypothesized that the CXC chemokine
      receptor 3 (CXCR3) may contribute to leukocyte accumulation and subsequently to
      blood vessel growth in the ischemic area. Ischemia induced by femoral artery
      ligature improved the number of CXCR3-expressing cells and the level of its
      ligand, CXCL10. Angiographic score, blood flow recovery measurement, and
      capillary density analysis showed a significant decrease of ischemic/nonischemic
      leg ratio in CXCR3-deficient mice when compared with controls (P<0.05), at day 21
      after ischemia. Interestingly, this impairment was as important as that observed
      in mice deficient for the well known CC-chemokine monocyte chemoattractant
      protein-1 (MCP-1). At day 7 of ischemic injury, the number of CD3-positive T
      cells and Mac-3-positive monocytes/macrophages was 38% and 45% lower,
      respectively, in the ischemic leg of CXCR3-deficient mice compared with the
      control group (P<0.05), suggesting an important role for CXCR3 in leukocyte
      recruitment into the ischemic area. VEGF protein content, a classical
      proangiogenic factor, was also markedly reduced (80% reduction) in ischemic leg
      of CXCR3-deficient mice (P<0.01). Injection of bone marrow-derived mononuclear
      cells (BM-MNCs) isolated from wild-type animals restored the neovascularization
      reaction in CXCR3-deficient mice whereas BM-MNCs from CXCR3-deficient mice was
      ineffective. In conclusion, CXCR3 plays a key role in neovascularization and
      provides novel information on the mechanisms leading to leukocyte infiltration in
      the vessel growth area.

PMID- 15718501
TI  - Metabolic inhibition alters subcellular calcium release patterns in rat
      ventricular myocytes: implications for defective excitation-contraction coupling
      during cardiac ischemia and failure.
AB  - Metabolic inhibition (MI) contributes to contractile failure during cardiac
      ischemia and systolic heart failure, in part due to decreased excitation
      contraction (E-C) coupling gain. To investigate the underlying mechanism, we
      studied subcellular Ca2+ release patterns in whole cell patch clamped rat
      ventricular myocytes using two-dimensional high-speed laser scanning confocal
      microscopy. In cells loaded with the Ca2+ buffer EGTA (5 mmol/L) and the
      fluorescent Ca2+-indicator fluo-3 (1 mmol/L), depolarization from -40 to 0 mV
      elicited a striped pattern of Ca2+ release. This pattern represents the
      simultaneous activation of multiple Ca2+ release sites along transverse-tubules.
      During inhibition of both oxidative and glycolytic metabolism using carbonyl
      cyanide-p-trifluoromethoxyphenylhydrazone (FCCP, 50 nmol/L) and 2-deoxyglucose (2
      DG, 10 mmol/L), there was a decrease in inward Ca2+ current (ICa), the spatially
      averaged Ca2+ transient, and E-C coupling gain, but no reduction in sarcoplasmic
      reticulum Ca2+ content. The striped pattern of subcellular Ca2+ release became
      fractured, or disappeared altogether, corresponding to a marked decrease in the
      area of the cell exhibiting organized Ca2+ release. There was no significant
      change in the intensity or kinetics of local Ca2+ release. The mechanism is not
      fully explained by dephosphorylation of L-type Ca2+ channels, because a similar
      degree of ICa"rundown" in control cells did NOT result in fracturing of the Ca2+
      release pattern. We conclude that metabolic inhibition interferes with E-C
      coupling by (1) reducing trigger Ca2+, and (2) directly inhibiting sarcoplasmic
      reticulum Ca2+ release site open probability.

PMID- 15718502
TI  - Cellular mechanism of calcium-mediated triggered activity in the heart.
AB  - Calcium overload due to enhanced calcium entry is a mechanism for spontaneous
      calcium release (SCR) from the sarcoplasmic reticulum, delayed
      afterdepolarizations (DAD), and triggered activity. However, the exact
      mechanistic relationship between elevated intracellular calcium levels and
      triggered activity originating from a specific location remains unclear. We
      hypothesize that under conditions of enhanced calcium entry, elevation of
      intracellular calcium will result in multiple calcium release events of which
      only one is more likely to initiate a triggered beat. We used optical mapping of
      action potentials and ratiometric calcium transients in an electromechanically
      uncoupled canine wedge model of enhanced calcium entry, using I(Ks) blockade with
      beta-adrenergic stimulation. Under conditions of enhanced calcium entry, the rate
      of calcium uptake was faster compared with control conditions; however, during
      rapid pacing, cytoplasmic calcium elevation at the endocardium was significantly
      increased (15+/-4%) compared with control (10+/-3, P<0.04). Rapid pacing induced
      multiple simultaneous SCR events with largest amplitude and earliest onset near
      the endocardium compared with the epicardium. Furthermore, SCR events with
      largest amplitude and earliest onset served as a focus for DAD-mediated triggered
      activity. Interestingly, polymorphic VT occurred in some experiments when
      multiple SCR events occurred. In conclusion, multiple, simultaneous SCR events
      occur over a broad region of relatively slower calcium uptake and elevated
      diastolic calcium levels. However, SCR events closer to the endocardium have the
      largest amplitude and earliest onset and are, thereby, more likely to initiate
      DAD-mediated triggered activity. Finally, multiple SCR events may be a mechanism
      of polymorphic VT under calcium overload conditions.

PMID- 15718504
TI  - Mixed messages: transcription patterns in failing and recovering human
      myocardium.
AB  - In previous studies, mechanical support of medically refractory hearts with a
      left ventricular assist device (LVAD) has induced regression of many
      morphological and functional abnormalities characteristic of failing human
      hearts. To identify transcriptional adaptations in failing and LVAD-supported
      hearts, we performed a comprehensive transcription analysis using the Affymetrix
      microarray platform and 199 human myocardial samples from nonfailing, failing,
      and LVAD-supported human hearts. We also used a novel analytical strategy that
      defines patterns of interest based on multiple intergroup comparisons. Although
      over 3088 transcripts exhibited significantly altered abundance in heart failure,
      most of these did not exhibit a consistent response to LVAD support based on our
      analysis. Of those 238 with a consistent response to LVAD support, more than 75%
      exhibited persistence or exacerbation of HF-associated transcriptional
      abnormalities whereas only 11%, 5%, and 2% exhibited partial recovery,
      normalization, and overcorrection responses, respectively. Even among genes
      implicated by previous reports of LVAD-associated myocardial improvements,
      partial or complete normalization of transcription did not predominate. The
      magnitude of differences in transcript abundance between nonfailing and failing
      hearts, and between failing an LVAD-supported hearts, tended to be low with
      changes greater than or equal to 2-fold infrequently observed. Our results
      indicate that morphological or functional myocardial improvements may occur
      without widespread normalization of pathological transcriptional patterns. These
      observations also suggest that many failure-associated transcriptional changes
      have only a limited role in regulating cardiac structure and function and may
      represent epiphenomena and/or nonspecific myocardial plasticity responses.
      Differences in mRNA localization, translation efficiency, and posttranslational
      protein modifications or interactions may be more pivotal in regulating
      myocardial structure and function.

PMID- 15718506
TI  - HGF and VEGF: a dynamic duo.

PMID- 15718503
TI  - A role for endoglin in coupling eNOS activity and regulating vascular tone
      revealed in hereditary hemorrhagic telangiectasia.
AB  - Decreased endothelial NO synthase (eNOS)-derived NO bioavailability and impaired
      vasomotor control are crucial factors in cardiovascular disease pathogenesis.
      Hereditary hemorrhagic telangiectasia type 1 (HHT1) is a vascular disorder
      associated with ENDOGLIN (ENG) haploinsufficiency and characterized by venous
      dilatations, focal loss of capillaries, and arteriovenous malformations (AVMs).
      We report that resistance arteries from Eng+/- mice display an eNOS-dependent
      enhancement in endothelium-dependent dilatation and impairment in the myogenic
      response, despite reduced eNOS levels. We have found that eNOS is significantly
      reduced in endoglin-deficient endothelial cells because of decreased eNOS protein
      half-life. We demonstrate that endoglin can reside in caveolae and associate with
      eNOS, suggesting a stabilizing function of endoglin for eNOS. After Ca2+-induced
      activation, endoglin-deficient endothelial cells have reduced eNOS/Hsp90
      association, produce less NO, and generate more eNOS-derived superoxide (O2-),
      indicating that endoglin also facilitates eNOS/Hsp90 interactions and is an
      important regulator in the coupling of eNOS activity. Treatment with an O2-
      scavenger reverses the vasomotor abnormalities in Eng(+/-) arteries, suggesting
      that uncoupled eNOS and resulting impaired myogenic response represent early
      events in HHT1 pathogenesis and that the use of antioxidants may provide a novel
      therapeutic modality.

PMID- 15718507
TI  - Wnt, a driver of myocardialization?

PMID- 15718508
TI  - Molecular determinants of vascular smooth muscle cell diversity.
AB  - Although the primary role of vascular smooth muscle cells (SMCs) is contraction,
      they exhibit extensive phenotypic diversity and plasticity during normal
      development, during repair of vascular injury, and in disease states. Results of
      recent studies indicate that there are unique as well as common transcriptional
      regulatory mechanisms that control expression of various SMC marker genes in
      distinct SMC subtypes, and that these mechanisms are complex and dynamic even at
      the single cell level. This article will review recent progress in our
      understanding of the transcriptional regulatory mechanisms involved in
      controlling expression of SMC marker genes with a particular focus on examination
      of processes that contribute to the phenotypic diversity of SMCs. In addition,
      because of considerable controversy in the literature regarding the relationship
      between phenotypically modulated SMCs and myofibroblasts, we will briefly
      consider both similarities and differences in regulation of gene expression
      between these cell types.

PMID- 15718509
TI  - Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for
      aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: The member 3 of clade A of serine proteinase inhibitors
      (SERPINA3), known previously as the alpha1-antichymotrypsin, is an acute phase
      protein, the levels of which increase in acute and chronic inflammation. The A/T
      polymorphism of the SERPINA3 gene influences expression of SERPINA3 protein.
      SERPINA3 can be related to aneurysmal subarachnoid hemorrhage (SAH) by
      influencing inflammation or by regulating cathepsin G activity. We studied the
      significance of SERPINA3 A/T polymorphism in patients with aneurysmal SAH
      compared with healthy controls. METHODS: A total of 180 patients with aneurysmal
      SAH and 263 healthy controls were genotyped for the SERPINA3 A/T polymorphism.
      Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture
      and digital subtraction angiography. SERPINA3 polymorphism was detected by
      polymerase chain reaction amplification and restriction enzyme digestion.
      RESULTS: The SERPINA3 genotype distribution in patients with aneurysmal SAH (AA
      29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70
      26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed
      that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95%
      CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84;
      P=0.009) of the SERPINA3 influences the risk for aneurysmal SAH independently
      from smoking, excessive alcohol consumption, and hypertension. CONCLUSIONS: The
      A/T polymorphism of SERPINA3 gene is associated with the risk factor for
      aneurysmal SAH.

PMID- 15718510
TI  - Reliability of the modified Rankin Scale across multiple raters: benefits of a
      structured interview.
AB  - BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS) is widely used to assess
      global outcome after stroke. The aim of the study was to examine rater
      variability in assessing functional outcomes using the conventional mRS, and to
      investigate whether use of a structured interview (mRS-SI) reduced this
      variability. METHODS: Inter-rater agreement was studied among raters from 3
      stroke centers. Fifteen raters were recruited who were experienced in stroke care
      but came from a variety of professional backgrounds. Patients at least 6 months
      after stroke were first assessed using conventional mRS definitions. After
      completion of initial mRS assessments, raters underwent training in the use of a
      structured interview, and patients were re-assessed. In a separate component of
      the study, intrarater variability was studied using 2 raters who performed repeat
      assessments using the mRS and the mRS-SI. The design of the latter part of the
      study also allowed investigation of possible improvement in rater agreement
      caused by repetition of the assessments. Agreement was measured using the kappa
      statistic (unweighted and weighted using quadratic weights). RESULTS: Inter-rater
      reliability: Pairs of raters assessed a total of 113 patients on the mRS and mRS
      SI. For the mRS, overall agreement between raters was 43% (kappa=0.25,
      kappa(w)=0.71), and for the structured interview overall agreement was 81%
      (kappa=0.74, kappa(w)=0.91). Agreement between raters was significantly greater
      on the mRS-SI than the mRS (P<0.001). Intrarater reliability: Repeatability of
      both the mRS and mRS-SI was excellent (kappa=0.81, kappa(w) > or =0.94).
      CONCLUSIONS: Although individual raters are consistent in their use of the mRS,
      inter-rater variability is nonetheless substantial. Rater variability on the mRS
      is thus particularly problematic for studies involving multiple raters. There was
      no evidence that improvement in inter-rater agreement occurred simply with
      repetition of the assessment. Use of a structured interview improves agreement
      between raters in the assessment of global outcome after stroke.

PMID- 15718511
TI  - Utility of outcome measures after treatment for intracranial aneurysms: a
      prospective trial involving 520 patients.
AB  - BACKGROUND AND PURPOSE: As different intracranial aneurysm treatments are
      compared in upcoming trials, complete characterization of patient outcomes will
      be critical. Currently, graded scales such as the Glasgow Outcome Score (GOS) or
      the Rankin scale are commonly used. Our objective was to test the utility of
      different outcome instruments in patients after aneurysm treatment. METHODS: A
      prospective trial comparing 6 outcome instruments at 3 to 12 months after
      aneurysm treatment: the Rankin and GOS, the Barthel Index (activities of daily
      living), the National Institutes of Health Stroke Score (NIHSS) (neurological
      examination), the Short Form-36 (subjective experience of recovery), and the Mini
      Mental Status Examination (MMSE) (cognitive recovery). All tests were
      administered to each patient at the same time by an independent grader. The
      Spearman correlation coefficient was calculated between instruments (with 1
      representing complete correlation). RESULTS: In 4 years, 520 patients with 618
      ruptured or unruptured aneurysms were enrolled: 385 surviving patients were
      tested. The resulting scores showed a wide distribution for the MMSE and the SF
      36, but almost no variability for the Barthel Index and NIHSS. Correlations
      between scores were poor: 0.15 when the GOS was compared with the MMSE; 0.27
      compared with the SF-36. Many patients given the highest GOS or Rankin scores
      showed significant cognitive deficits. CONCLUSIONS: These data indicate that a
      single graded scale does not address all aspects of recovery after aneurysm
      treatment, particularly cognitive dysfunction and the patient's perception of
      health. The implications of these findings are discussed.

PMID- 15718512
TI  - Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous
      malformation lesion.
AB  - BACKGROUND AND PURPOSE: Cerebral cavernous malformations (CCMs) are focal
      dysmorphic blood vessel anomalies that predispose patients to hemorrhagic stroke
      and epilepsy. CCMs are sporadic or inherited and 3 genes (CCM1, CCM2, and CCM3)
      have been identified. However, the role of somatic mutation in CCM genesis has
      been disputed. The hypothesis that somatic mutations contribute to CCM lesion
      genesis is tested. METHODS: Mutations were identified by analysis of polymerase
      chain reaction (PCR) products spanning the 16 CCM1 coding exons with denaturing
      high-pressure liquid chromatography (DHPLC), cloning, and sequencing. Somatic
      mutation was verified 3 ways in lesion DNA and RNA samples. The somatic and germ
      line mutations were shown to be biallelic using allele specific reverse
      transcribed PCR amplification and sequence analyses. RESULTS: A somatic 34
      nucleotide deletion in CCM1 is identified in a CCM lesion along with a germ line
      CCM1 mutation (Q455X). The somatic mutation is not present in DNA or RNA isolated
      from the patient's blood. These 2 genetic hits are biallelic. CONCLUSIONS:
      Identification of biallelic CCM1 somatic and germ line truncating mutations
      strongly support the "two-hit" mechanism in this CCM lesion.

PMID- 15718515
TI  - Suicide, depression, and antidepressants.

PMID- 15718516
TI  - Clinical and communication skills.

PMID- 15718517
TI  - Low level alcohol consumption and the fetus.

PMID- 15718518
TI  - Neglected diseases.

PMID- 15718519
TI  - The treatment of lupus nephritis.

PMID- 15718521
TI  - Shortage of surgeons might threaten NHS targets.

PMID- 15718525
TI  - Barrier in West Bank threatens residents' health care, says report.

PMID- 15718522
TI  - Woman seeks approval to use frozen embryos.

PMID- 15718529
TI  - Medical courts could ease US malpractice crisis, group says.

PMID- 15718537
TI  - Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta
      analysis of drug company data from placebo controlled, randomised controlled
      trials submitted to the MHRA's safety review.
AB  - OBJECTIVE: To investigate whether selective serotonin reuptake inhibitor (SSRI)
      antidepressants are associated with an increased risk of suicide related outcomes
      in adults. DESIGN: Meta-analysis of randomised controlled trials of SSRIs
      compared with placebo in adults submitted by pharmaceutical companies to the
      safety review of the Medicines and Healthcare products Regulatory Agency (MHRA).
      PARTICIPANTS: Over 40,000 individuals participating in 477 randomised controlled
      trials. MAIN OUTCOME MEASURES: Suicide, non-fatal self harm, and suicidal
      thoughts. RESULTS: An estimated 16 suicides, 172 episodes of non-fatal self harm,
      and 177 episodes of suicidal thoughts were reported. We found no evidence that
      SSRIs increased the risk of suicide, but important protective or hazardous
      effects cannot be excluded (odds ratio 0.85, 95% credible interval 0.20 to 3.40).
      We found weak evidence of an increased risk of self harm (1.57, 0.99 to 2.55).
      Risk estimates for suicidal thoughts were compatible with a modest protective or
      adverse effect (0.77, 0.37 to 1.55). The relative frequency of reported self harm
      and suicidal thoughts in the trials compared with suicide indicates non-fatal end
      points were under-recorded. CONCLUSION: Increased risks of suicide and self harm
      caused by SSRIs cannot be ruled out, but larger trials with longer follow up are
      required to assess the balance of risks and benefits fully. Any such risks should
      be balanced against the effectiveness of SSRIs in treating depression. When
      prescribing SSRIs, clinicians should warn patients of the possible risk of
      suicidal behaviour and monitor patients closely in the early stages of treatment.

PMID- 15718538
TI  - Antidepressant treatment and the risk of fatal and non-fatal self harm in first
      episode depression: nested case-control study.
AB  - OBJECTIVE: To compare the risk of non-fatal self harm and suicide in patients
      taking selective serotonin reuptake inhibitors (SSRIs) with that of patients
      taking tricyclic antidepressants, as well as between different SSRIs and
      different tricyclic antidepressants. DESIGN: Nested case-control study. SETTING:
      Primary care in the United Kingdom. PARTICIPANTS: 146,095 individuals with a
      first prescription of an antidepressant for depression. MAIN OUTCOME MEASURES:
      Suicide and non-fatal self harm. RESULTS: 1968 cases of non-fatal self harm and
      69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was
      0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to
      1.25) in people prescribed SSRIs compared with those prescribed tricyclic
      antidepressants. We found little evidence that associations differed over time
      since starting or stopping treatment. We found some evidence that risks of non
      fatal self harm in people prescribed SSRIs compared with those prescribed
      tricyclic antidepressants differed by age group (interaction P = 0.02). The
      adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared
      with users of tricylic antidepressants for those aged 18 or younger was 1.59
      (1.01 to 2.50), but no association was apparent in other age groups. No suicides
      occurred in those aged 18 or younger currently or recently prescribed tricyclic
      antidepressants or SSRIs. CONCLUSION: We found no evidence that the risk of
      suicide or non-fatal self harm in adults prescribed SSRIs was greater than in
      those prescribed tricyclic antidepressants. We found some weak evidence of an
      increased risk of non-fatal self harm for current SSRI use among those aged 18 or
      younger. However, preferential prescribing of SSRIs to patients at higher risk of
      suicidal behaviour cannot be ruled out.

PMID- 15718541
TI  - Locked-in syndrome.

PMID- 15718539
TI  - Association between suicide attempts and selective serotonin reuptake inhibitors:
      systematic review of randomised controlled trials.
AB  - OBJECTIVE: To establish whether an association exists between use of selective
      serotonin reuptake inhibitors (SSRIs) and suicide attempts. DESIGN: Systematic
      review of randomised controlled trials. DATA SOURCES: Medline and the Cochrane
      Collaboration's register of controlled trials (November 2004) for trials produced
      by the Cochrane depression, anxiety, and neurosis group. SELECTION OF STUDIES:
      Studies had to be randomised controlled trials comparing an SSRI with either
      placebo or an active non-SSRI control. We included clinical trials that evaluated
      SSRIs for any clinical condition. We excluded abstracts, crossover trials, and
      all trials whose follow up was less than one week. RESULTS: Seven hundred and two
      trials met our inclusion criteria. A significant increase in the odds of suicide
      attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to
      harm 684) was observed for patients receiving SSRIs compared with placebo. An
      increase in the odds ratio of suicide attempts was also observed in comparing
      SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94,
      1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic
      antidepressants, we did not detect a difference in the odds ratio of suicide
      attempts (0.88, 0.54 to 1.42). DISCUSSION: Our systematic review, which included
      a total of 87 650 patients, documented an association between suicide attempts
      and the use of SSRIs. We also observed several major methodological limitations
      in the published trials. A more accurate estimation of risks of suicide could be
      garnered from investigators fully disclosing all events.

PMID- 15718543
TI  - Epidemiology of health and illness.

PMID- 15718542
TI  - Use of antibiotics in suspected haemolytic-uraemic syndrome.

PMID- 15718546
TI  - Rethinking childhood depression: treatment options may be limited by resources.

PMID- 15718544
TI  - Timers on ventilators.

PMID- 15718547
TI  - Rethinking childhood depression: consider what it means to be a child these days.

PMID- 15718548
TI  - Rethinking childhood depression: does childhood depression exist?

PMID- 15718549
TI  - Biomedical models and healthcare systems: tangible pathology has great validity.

PMID- 15718550
TI  - Biomedical models and healthcare systems: developmental perspective may elucidate
      argument.

PMID- 15718551
TI  - Biomedical models and healthcare systems: new model will be useful if it alters
      allocation of resources.

PMID- 15718552
TI  - Selective serotonin reuptake inhibitors: THREAD trial may show way forward.

PMID- 15718553
TI  - Selective serotonin reuptake inhibitors: placebo washouts inflate antidepressant
      effects in general practice.

PMID- 15718554
TI  - Selective serotonin reuptake inhibitors: evidence base for older antidepressants
      is shaky too.

PMID- 15718555
TI  - Trial protocols: time for more than tinkering.

PMID- 15718556
TI  - The Mexico Summit on Health Research 2004: medical community in developing
      countries has duty to promote healthcare research.

PMID- 15718557
TI  - The Mexico Summit on Health Research 2004: Mexico agenda was informed by wide
      consultation.

PMID- 15718559
TI  - Introduction: how we got here.

PMID- 15718560
TI  - The case for eHealth.

PMID- 15718561
TI  - National infrastructure for eHealth: considerations for decision support.

PMID- 15718562
TI  - Sjunet--the national IT infrastructure for healthcare in Sweden.
AB  - Sjunet is the Swedish Health Care Network comprising an infrastructure for
      communication between hospitals, primary care centres and home care. It is also
      hosting a wide range of services from national authorities and health care
      service providers and vendors of health care systems. Sjunet allows secure
      transmission of health care data and applications on an IP-network separate from
      the Internet. The network is used for telemedical videoconferences,
      teleradiology, remote access to applications, database access, secure e-mail, EDI
      messages and IP telephony. It is also useful for e-learning in medical education
      and further training for health personnel. Carelink is responsible for Sjunet in
      close co-operation with the county councils and other actors within Sjunet.
      Hence, Sjunet is as much a co-operative network as it is a technical
      communication platform for Swedish health care.

PMID- 15718563
TI  - Building the regional eHealth network. The Andalusian experience.

PMID- 15718565
TI  - HYGEIAnet: the integrated regional health information network of Crete.
AB  - The healthcare environment is currently changing and the health sector is being
      transformed to meet new challenges and to benefit from new opportunities.
      Priorities for the 21st century ought to be set based on emerging dominant trends
      in healthcare, including the shift towards shared or integrated care, in which an
      individual's healthcare is the responsibility of a team of professionals across
      all levels of the healthcare system hierarchy. In addition to the requirement for
      efficient and secure access to the Integrated Electronic Health Record (I-EHR) of
      a citizen, this necessitates the development and deployment of Regional Health
      Information Networks (RHINs), synchronous and asynchronous collaboration
      services, and novel eHealth and mHealth services, facilitated by intelligent
      sensors, monitoring devices, hand-held or wearable technologies, the Internet and
      wireless broadband communications. These further require the adoption of an open
      Reference Architecture and the creation of a scalable Health Information
      Infrastructure (HII).This paper discusses the challenges encountered in
      developing and deploying HYGEIAnet, the Regional Health Information Network of
      Crete, as well as relevant benefits for citizens and health professionals.
      Furthermore, HYGEIAnet systems and services are presented, with emphasis on the
      development of the HII and the implementation of the I-EHR service for providing
      secure, role-based access to validated content by authorized and authenticated
      users.

PMID- 15718564
TI  - MedCom: Danish health care network.
AB  - The Danish Ministry of Health founded MedCom back in 1994. MedCom is acting as an
      umbrella project organisation, gathering health providers, health care
      professionals and industry in coordinated, nationwide projects, all aiming to
      reach large-scale dissemination in few years. Almost all Danish health care
      organisations and IT-vendors are participating in the projects and today more
      than 2,500 health institutions are communicating around 2.3 million messages
      monthly--60% of the total clinical "cross-sector" communication in Danish Health.
      In the next years the standards are going to be reused inside hospitals and a
      nationwide secure health care Internet implemented large scale.

PMID- 15718566
TI  - Northern Norwegian Health Net.
AB  - Northern Norwegian Health Net (the Net) is a closed network for social and health
      care institutions in North Norway. In its present form it was established in
      2000, but the early start was in the late 1980s. This proceeding will give a
      brief history of the network, description of the technology used and the services
      offered. It also gives a summary of experiences with the Net and research
      conducted on the services. Most health care institutions in the region are
      connected in the Net, and the usage is increasing.

PMID- 15718567
TI  - North Karelia regional chain of care: Finnish experiences.
AB  - Information--and communication technology is one of the most important
      cornerstones in more and more data and knowledge intensive health care sector.
      However these factors don't create financial gains and productivity benefits
      spontaneously. They need organisational and social innovations and new business
      models. The growth of productivity is connected to the process and organisational
      innovations and not to the number of computers and the growth of using ICT. One
      of the problems prohibiting health care profession to move to real e-work
      environment is the lack of the reliable measures and on these measures based
      performance measurement and strategic management. Health care can be improved by
      utilizing ICT and tools like performance measuring are key weapons in the arsenal
      of new e-work environment and measuring based new strategic management. Neither
      public sector nor not-for-profit hospitals look for financial rewards as their
      ultimate proof of success. Instead, they seek to achieve ambitious missions aimed
      at improving the health standards and wellbeing of the citizens. ICT- based new
      way of managing in the public sector is just beginning to gain a critical level
      of digitalization and will most likely come to its own in the coming years.
      Therefore, it is essential to research on how the health care sector can be moved
      towards new regional models and clinical workflow using intelligent standard
      based strategic management and performance measurement. If the breakthrough of
      the eight-hour working day and shortening of working time are evaluated
      afterwards, it can be stated that they have made the society more anthropocentric
      and humane. During one century the annual working time has shortened from 3000
      hours to 1700 hours in the European Union countries. These foundations of a more
      humane society--eight-hour working day and shortening of regular working time-
      are however disappearing in the post-industrialized information society. There
      are various grounds for the eight-hour working day. These grounds relate to
      quality of life, occupational safety and health and productivity of work. It is
      worth asking if the nature of work has changed in a way that the truths of an
      industrialized society do not hold true or has the development of working time in
      health care sector become uncontrolled in some new way?

PMID- 15718568
TI  - UUMA. Regional eHealth services in the hospital district of Helsinki and Uusimaa
      (HUS).
AB  - The UUMA approach is based on a stepwise implementation of integrated regional
      healthcare services to create a virtually borderless healthcare organisation--a
      patient centred virtual workspace. In the virtual workspace multi-professional
      teams and patients collaborate and share information regardless of time and
      place. Presently the regional ehealth network is comprised of four different
      integrated services between primary, secondary and tertiary care within the
      county of Uusimaa. The strategic healthcare modules consist of an (1) ereferral
      and econsultation network, (2) a knowledge-based disease management platform, (3)
      PACS system and (4) a universal model for integrated regional services between
      professionals and patients by a link directory service. The ereferral between
      primary and secondary care not only speeds up the transfer, but also offers an
      option for communication in the form of econsultation between general
      practitioners and hospital specialists. By sharing information and knowledge
      remote econsultations create a new working environment for integrated delivery of
      eServices between the health care providers. Last year over 60,000 eReferrals
      were transferred between health care providers. When associated with viewing of
      patient data through the link directory, interactive econsultations enable
      supervised care leading to the reduction of outpatient visits and more timely
      appointments. The link directory service extends the dimensions of networking
      between organizations by combining legacy systems within regional primary and
      secondary care. The link directory is an interface to diverse patient information
      systems, like HUSpacs, containing links pointing to the actual patient data
      located in remote information systems. The original data including images can be
      viewed with a web browser, but data can be accessed only with the patient's
      informed consent. The chronic disease management system is disease specific:
      information is utilised in parallel to viewing other relevant medical data
      through the link directory. We aim to create a new working environment for
      professionals by incorporation of innovative information and communication
      technology, new organisation of work and re-engineering of workflows. The citizen
      has an active role in deciding on the use of his medical information,
      participating in decisions on his care, carrying out guided self-care and taking
      steps of pro-active prevention.

PMID- 15718569
TI  - Telemedicine--contribution of ICT to health.
AB  - ICT opens new possibilities to health care and practice of medicine, but carries
      some inherent risks as well. Based on a study conducted by the CPME representing
      European doctors current telemedical practices and difficulties encountered by
      doctors are reported and next important steps are proposed. An European e-Health
      Highway should be built and obligatory standards for it and for all software used
      in the health care should be urgently fixed. The medical profession should take
      care of practical guidelines for doctors, and authorities should agree on
      international collaboration to supervise the practice of medicine over the net.
      Telemedicine should be a normal part of the national healthcare systems, and
      telemedical services should be reimbursed as any other medical services.

PMID- 15718570
TI  - SURGETICA at Grenoble: from computer assisted medical interventions to quality
      inspired surgery.
AB  - Research on "Computer Assisted Medical Interventions" (CAMI) was initiated in
      Grenoble in 1984, as an attempt to take up the challenge of "Minimally Invasive
      Interventions", thanks to the introduction of Information and Communication
      Techniques in the Operating Room. In a first section, we will describe our
      initial vision. The corresponding achievements will then be presented. A final
      section will show that the challenge now is to "invert this movement": instead of
      moving the computer in the Operating Room, we should embed the surgeon (or at
      least his or her expertise) into the Information Technology based tools he or she
      uses.

PMID- 15718571
TI  - The Oxford clinical intranet: providing clinicians with access to patient records
      and multiple knowledge bases with internet technology.
AB  - The Oxford Clinical Intranet provides clinicians in primary and secondary care
      across Oxfordshire with: Access to information about their patients held on
      multiple remote disparate computer systems, including admissions and episodes,
      Laboratory Medicine reports, Radiology reports and hospital discharge letters.
      The patient records are managed using CSW Case Notes. Access to support and
      advisory information, developed both within the organization and collected from
      other sites and projects, a wide range of internal handbooks, directories and
      guidelines and links to external resources, including evidence-based resources,
      the Cochrane Collaboration and the NHS National electronic Library of Health.
      Automated retrieval and presentation of the support information that is
      contextually appropriate to the task being carried out by the clinician and the
      information held about the patient. For example laboratory reports are linked to
      handbooks and other reference sources using eLABook, a web-interfaced database
      subsystem. Internet technology has been used throughout, thus providing a thin
      client architecture with cross-platform ability. Appropriate data standards have
      been used across the communicating systems and the intranet is compliant with the
      UK eGovernment Interoperability Framework. The intranet was developed at low cost
      and is now in routine use. This approach appears to be transferable across
      systems and organisations.

PMID- 15718572
TI  - The contribution of ICT to health: the Andalusian Health Network.

PMID- 15718573
TI  - From SARS to systems: developing advanced knowledge management for public health.
AB  - Historically, public health has been at the forefront of data processing
      applications but it is lagging behind other areas of health care in the
      application of advanced interconnected and mobile information technologies. Ready
      to use technologies are lacking not only for the management of emerging
      infections or bio-terrorism but also for the coordination of prevention and
      chronic care initiatives. Advanced information and knowledge management for
      community health should expedite the transfer of research evidence to practice
      and provide essential logistical support for action. We need to find ways to
      integrate new scientific knowledge into our environment in order to expedite the
      translation of research to practice.

PMID- 15718574
TI  - Realizing the potential of the internet for health and medical information.
AB  - The latest advances in information technologies have allowed for the development
      of applications that have had tremendous repercussions in the healthcare field.
      Along with access, means must be provided to ensure that information is
      trustworthy and relevant. This article examines some of the problems arising from
      unprecedented access to vast quantities of health information made possible by
      the Internet. The role of search engines is explored and some of their associated
      problems are mentioned. We then presents the most mature of these initiatives to
      protect the Internet citizen, the HONcode, developed by the Health On the Net
      Foundation. Finally, we conclude on the concrete result of the Health On the Net
      Foundation initiatives since 1997.

PMID- 15718575
TI  - NHS Direct Online: a multi-channel eHealth service.
AB  - In the UK NHS Direct has developed a multi-channel e-health service for patients
      and the public. NHS Direct is enabling patient and citizen opportunities for fast
      access to information by using 24 hour telephone call centres, the web, digital
      interactive tv and public touch screen kiosks. This multi-channel strategy is
      based on the principle of providing people with maximum choice in the route by
      which they access information, with the assurance of consistent high quality
      information whichever channel they choose.

PMID- 15718576
TI  - Area wide electronic booking: a revolution in the management of health and well
      being.
AB  - Area wide electronic booking provides patients with the choice of date, time and
      place as well as the certainty of appointment when referred into secondary care
      by their GP. The system provides substantial benefits to both primary and
      secondary care as well as to the patient. This model is to be imminently
      implemented throughout the NHS in England, drawing from the experiences gained in
      South East London.

PMID- 15718577
TI  - Slovene national insurance card system: connecting patient and health care.
AB  - The paper outlines a case of an implemented modern IT solution in the health
      care, that is, the Slovene health insurance card system. The system is in full
      operation nation-wide and covers all the aspects of health care and health
      insurance operations. The system allows reliable identification of patients and
      service providers and, with its design open to enhancements, is a major
      breakthrough in the process of transition to e-health. The paper addresses both
      the national and international perspective of such IT solutions, with the main
      issues and goals being the quality of services to the citizen, the health care
      system economics and management, and the free movement of people and services in
      the internal market. Special consideration is devoted to the compatibility and
      interoperability of national systems with the emerging European health insurance
      card. Furthermore, the paper outlines the main financial dimensions of the
      development to date and the changes achieved through the intensive development in
      terms of quality and accessibility of health care services.

PMID- 15718578
TI  - Sustains--direct access for the patient to the medical record over the Internet.
AB  - The basic idea of Sustains III is to emulate the Internet banking for Health
      Care. Instead of an "Internet Bank Account" the user has a "Health Care Account".
      The user logs in using a One Time Password which is sent to the user's mobile
      phone as an SMS, three seconds after the PIN code is entered. Thus personal
      information can be transferred both ways in a secure way, with acceptable
      privacy. The user can then explore the medical record in detail. Also get full
      and complete list of prescriptions, lab-result etc. It's also an easy way of
      exchange written information between the doctor and the patient. So far Sustains
      has showed that patients are very satisfied and is also beneficial for the
      physicians.

PMID- 15718579
TI  - Advanced technology permits the provision of advanced hospital care in the
      patients' homes.
AB  - Improvements in disease management and the aging of populations in Western
      countries are the main factors that have resulted in a disquieting rise in demand
      for expensive hospital beds. The patient-centred and family-friendly concept
      "Hospital at Home" has recently appeared on the global scene of health services,
      promising to offer a solution. This type of service has proved to be very welcome
      to patients and those they live with. However, Hospital at Home schemes reported
      in the literature are organized only to provide improved primary care services,
      usually to patients who are discharged from hospital a few days early and for the
      rest of their treatment. These services are mainly provided by nurses who perform
      one or fewer home visits a day and the medical contribution, if any, is limited
      to telephone consultations when necessary. Whenever something unusual happens the
      patient is readmitted. Some Hospital at Home settings, which are characterized as
      "admission avoidance", actually include only patients with conditions so stable
      that they might have stayed at home anyway, with some good primary care support.
      Yet Hospital at Home has much more to offer. Incorporated in the administrative
      structure of a hospital as real wards, manned with doctors, nurses and other
      health professionals on 24-hour duty in shifts and providing frequent--at least
      twice a day--regular home visits by doctors and nurses, Hospital at Home can
      reproduce real hospital conditions in the patients' homes. Portable medical
      devices enable the performance of a wide range of examinations at home, while
      information and communication technology neutralizes distances and makes
      collaboration between the virtual team and other contributors feasible and
      effective. Almost any patient whose condition neither requires prompt surgical
      operation nor meets the criteria for admission to an intensive care unit can be
      safely hospitalised at home, provided that he is attended by a properly
      organized, properly equipped and highly alert Hospital at Home service.

PMID- 15718580
TI  - Boario home care project.

PMID- 15718581
TI  - User perspective of DITIS: virtual collaborative teams for home-healthcare.
AB  - DITIS supports home-care by offering wireless health care services for chronic
      illnesses. The main service is the dynamic creation, management and co-ordination
      of virtual collaborative healthcare teams for the continuous treatment of the
      patient at home, independently of the physical location of the team's members (or
      the patient). For each patient a flexible (dynamic) virtual medical team is
      provided, made up from visiting home-care nurses, doctors, and other health care
      professionals, responsible for each case. This virtual team is able to provide
      dedicated, personalized and private service to the home residing patient on a
      need based and timely fashion, under the direction of the treating specialist,
      without the necessity to move the patient from his home, thus making better use
      of the scarce and expensive medical professionals and scarce hospital beds,
      irrespective of geographic or organisational barriers. DITIS uses a number of
      state of the art technologies which are seamlessly put together, such as
      collaboration and personalization via mobile agents, access to medical data from
      anywhere and any time via a variety of mobile devices and a variety of protocols
      (i.e., WAP, HTML) and continuous connectivity via new communication technologies
      such as ADSL and GPRS, and soon UMTS. All the technologies are selected for
      platform independence.

PMID- 15718582
TI  - eHealth 2003: the economic and user perspective.
AB  - People's desire is quite simple: They want to stay as healthy as possible. The
      aim of healthcare is to help make this desire a reality. Innovations have
      substantially supported healthcare providers' in their efforts to increase the
      quality of care. To continue to make significant improvements--even under
      difficult socio-economic circumstances--healthcare must now become more process
      oriented throughout the complete care process, i.e. from early detection to cure.
      Modern information and communication technology, i.e. eHealth, is the key to
      optimize processes within the entire healthcare system and to provide higher
      quality care at less cost. Quantifiable proven outcomes that clearly demonstrate
      the efficiency of eHealth are being realized. Action and co-operation between all
      healthcare players is necessary to structure and enable healthcare in a way that
      allows all people to benefit from the tremendous potential for progress that
      information technology offers to healthcare.

PMID- 15718583
TI  - Introduction to industrial perspectives: eHealth systems, past experiences and
      future prospects.
AB  - In this paper some of Philips' experiences in the domain of eHealth will be
      described. The main premise however will be that the next major step forward will
      require a much more ubiquitous and pervasive infrastructure around Electronic
      Patient Records, giving the patient a much more important role in managing his or
      her own health.

PMID- 15718584
TI  - e-Health standardization in Europe: lessons learned.
AB  - Challenges regarding standardization in e-Health are analyzed, and solutions for
      ensuring their practical implementation are proposed. Emphasis is put on new
      mechanisms for enhancing the collaboration between the industry and
      standardization bodies.

PMID- 15718585
TI  - The cost benefit of electronic patient referrals in Denmark: summary report.
AB  - This summary report is written by ACCA and MedCom in collaboration with the
      European Commission Information Society Directorate-General.

PMID- 15718586
TI  - The road ahead.
AB  - The recent events dedicated to eHealth, such as eHealth 2003 and eHealth 2004
      Ministerial conferences and exhibition, demonstrated clearly that a critical mass
      of users is being created who already use eHealth services and applications.
      Citizens, patients and health professionals are experiencing growing benefits
      from the use of eHealth applications which can increase citizen information,
      increase patient empowerment, speed up delivery, and reduce medical risks. Yet
      despite their availability and proven benefits, eHealth systems and services are
      not yet widely used in real-life medical or health situations. In many places,
      development is still at a pilot phase, often financed through research grants.

PMID- 15718588
TI  - Value-driven management in e-healthcare.
AB  - Web systems present executives with a new variant of an old problem: determining
      "What am I getting out of this communication technology implementation?" The
      creation of a set of value criteria is vital. The main aim of the paper is to
      modify the approach suggested by Kaplan-Norton, emphasizing the value chain
      processes and other development aspects important for e-healthcare (patient
      satisfaction, finance, knowledge and technology). The paper contains the
      definition of the value generated in an e-healthcare system. The paper develops
      M. Porter's value chain approach and contains a model value chain for an e
      healthcare organisation. This approach explains the activities behind the
      generation of value.

PMID- 15718589
TI  - Technical aspects of portal technology application for e-health systems.
AB  - E-health is an emerging field on the intersection of medical information
      technologies, public health and business, referring to health services and
      information delivered or enhanced through the Internet and related technologies.
      Portal technology, allowing services to be accessible over the Internet is a
      perfect tool for providing e-health services. The use of portal technologies has
      had deep influence on the architecture of the whole e-health system, both
      regarding new subsystems and older ones which we want to integrate with the
      portal. Portals provide new possibilities for creating novel types of e-health
      applications as well. In this paper we provide a brief overview of e-health
      systems and portal technologies, and present many technical aspects of portal
      technology application for e-health systems such as the architecture of portal
      based e-health systems, graphical user interfaces, access to various e-health
      systems' resources, personalization, security and privacy.

PMID- 15718590
TI  - Medical information asymmetry in the cyberworld of manuel castells.
AB  - Before 1997, the Internet was strongly associated with universities and higher
      education, including medical research. There were only small virtual communities
      at that time, but all their members had equal access to the entire body of
      information placed on the net. Each networking participant was able not only to
      retrieve but also to create and distribute medical information. This state was a
      symmetry, of sorts, between passive and active Internet usage. Since that time,
      however, significant commercialization of the Internet (including the medical
      domain) has been increasing its asymmetry. We currently observe a division into
      providers, serving and distributing medical information on the net, and
      consumers, who receive pre-prepared "products". This brings new challenges for
      both academic and practicing e-health physicians. First, while all large-scale
      initiatives to certify medical portals have so far failed, the public must be
      educated to chose valuable, high quality medical information themselves.
      Secondly, this imbalance favors abusive commercial behavior, such as spam,
      spreading viruses and advertising without content-related information.
      Stimulating a restoration of the previous idea of the Internet for non-profit
      activities seems to be best way to avoid the continuation of Internet
      "degeneration". Manuel Castells has defined future industrial and postindustrial
      progress of humanity as activity in global virtual communities, interchanging
      ideas, knowledge and information. The role of medical professionals seems to be
      to educate patients and their families on how to search for quality medical
      information and to stimulate other medical professionals, researchers as well as
      patients' supportive groups to be active themselves. Reducing the medical
      information asymmetry will provide a positive influence on the progress of e
      health in the future. Open source software may help reduce costs by creating
      adequate resources.

PMID- 15718591
TI  - Web-based health services and clinical decision support.
AB  - The purpose of this study was the development of a Web-based e-health service for
      comprehensive assistance and clinical decision support. The service structure
      consists of a Web server, a PHP-based Web interface linked to a clinical SQL
      database, Java applets for interactive manipulation and visualization of signals
      and a Matlab server linked with signal and data processing algorithms implemented
      by Matlab programs. The service ensures diagnostic signal- and image analysis
      sbased clinical decision support. By using the discussed methodology, a pilot
      service for pathology specialists for automatic calculation of the proliferation
      index has been developed. Physicians use a simple Web interface for uploading the
      pictures under investigation to the server; subsequently a Java applet interface
      is used for outlining the region of interest and, after processing on the server,
      the requested proliferation index value is calculated. There is also an "expert
      corner", where experts can submit their index estimates and comments on
      particular images, which is especially important for system developers. These
      expert evaluations are used for optimization and verification of automatic
      analysis algorithms. Decision support trials have been conducted for ECG and
      ophthalmology ultrasonic investigations of intraocular tumor differentiation.
      Data mining algorithms have been applied and decision support trees constructed.
      These services are under implementation by a Web-based system too. The study has
      shown that the Web-based structure ensures more effective, flexible and
      accessible services compared with standalone programs and is very convenient for
      biomedical engineers and physicians, especially in the development phase.

PMID- 15718592
TI  - Accessibility of public Web sites - the InHand case study.
AB  - Access to information and communication systems for PwD (Persons with
      Disabilities) is a priority both for the EU and candidate countries. This paper
      presents some results of the Romanian project called "InHand - Information Center
      for Persons with Disabilities)". The main goal of the project is to contribute to
      improving the quality of life and health status of this group of people. Our
      emphasis is on the benefits of universal design. By eliminating barriers that
      prevent people with disabilities from using Web sites, it is possible to make
      each site more useful for all visitors, not to mention ease of maintenance and
      cost-effectiveness.

PMID- 15718593
TI  - Establishing an internet-based paediatric cancer registration and communication
      system for the Hungarian paediatric oncology network.
AB  - Cancer registration has developed in Europe over the last 50 years, and in the
      last decade intensive joint activities between the European Cancer Registries, in
      response to the need of pan-European harmonization of registration practices,
      have taken place. The Hungarian Paediatric Cancer Registry has been functioning
      as the database of the Hungarian Paediatric Oncology Network since 1971, aiming
      to follow the incidence and the treatment efficacy of malignant diseases. The
      goals of this globally unique open source information system are the following:
      1) to raise the quality of the registration system to the European level by
      developing an Internet-based registration and communication system, modernizing
      the database, establishing automatic statistical analyses and adding an Internet
      website, 2) to support clinical epidemiological studies that we conduct with
      international collaborators on detailed analyses of the characteristics of
      patients and their diseases, evaluation of new diagnostic and therapeutic
      methods, prevention programs, and long-term quality of life and side effects. The
      benefits of the development of the Internet-based registration and communication
      system are as follows: a) introduction of an Internet-based case reporting
      system, b) modernization of the registry database according to international
      recommendations, c) automatic statistical summaries, encrypted mail systems,
      document repository, d) application of data security and privacy standards, e)
      establishment of a website and compilation of educational materials. The overall
      objective of this scientific project is to contribute towards the improvement of
      cancer prevention and cancer care for the benefit of the public in general and of
      cancer patients in particular.

PMID- 15718594
TI  - Telemedical database of Hodgkin's disease.
AB  - The creation of a complex telemedical system oriented towards childhood Hodgkin's
      disease has been undertaken at the Department of Bioinformatics and Telemedicine
      of the Jagiellonian University Medical College in cooperation with the Department
      of Oncology and Pediatric Hematology of the Polish-American Institute of
      Pediatrics, JU MC. Data collecting, data processing and data transmission is
      aimed to aid and/or supervise surgical and drug treatment. The Tele-Database of
      Childhood Hodgkin's Disease (TDCHD) is not a simple Internet database project. A
      few hundred data items are presented in each patient's record, covering the
      complete medical treatment period. Efficient management and proper data
      protection are necessary for a medical database. Therefore, the interface for
      entering data has been divided into several parts. Each part is subjected to
      separate editing and transfer. A double-layer debugging system has been applied
      in the program: the first pass occurs on the client side (programmed in
      JavaScript and XML), the second - on the server side (programmed in PHP). Strict
      authorization is requested for all participants. Clinical data collected
      according to management standards and information governance (data quality,
      security and confidentiality) is organized in a way that facilitates practical
      and scientific use.

PMID- 15718595
TI  - New developments in digital pathology: from telepathology to virtual pathology
      laboratory.
AB  - AIMS: To analyse the present status and future development of computerized
      diagnostic pathology in terms of work-flow integrative telepathology and virtual
      laboratory. PRESENT STATUS: Telepathology has left its childhood. The technical
      development of telepathology is mature, in contrast to that of virtual pathology.
      Two kinds of virtual pathology laboratories are emerging: a) those with
      distributed pathologists and distributed (>=1) laboratories associated to
      individual biopsy stations/surgical theatres, and b) distributed pathologists
      working in a centralized laboratory. Both are under technical development.
      Telepathology can be used for e-learning and e-training in pathology, as
      exemplarily demonstrated on Digital Lung Pathology Pathology (www.pathology
      online.org). FEATURES OF VIRTUAL PATHOLOGY: A virtual pathology institution (mode
      a) accepts a complete case with the patient's history, clinical findings, and
      (pre-selected) images for first diagnosis. The diagnostic responsibility is that
      of a conventional institution. The internet serves as platform for information
      transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch)
      for coordination and performance of the diagnostic procedure. The size of images
      has to be limited, and usual different magnifications have to be used. A group of
      pathologists is "on duty", or selects one member for a predefined duty period.
      The diagnostic statement of the pathologist(s) on duty is retransmitted to the
      sender with full responsibility. First experiences of a virtual pathology
      institution group working with the iPATH server (Dr. L. Banach, Dr. G. Haroske,
      Dr. I. Hurwitz, Dr. K. Kayser, Dr. K.D. Kunze, Dr. M. Oberholzer,) working with a
      small hospital of the Salomon islands are promising. A centralized virtual
      pathology institution (mode b) depends upon the digitalisation of a complete
      slide, and the transfer of large sized images to different pathologists working
      in one institution. The technical performance of complete slide digitalisation is
      still under development and does not completely fulfil the requirements of a
      conventional pathology institution at present. VIRTUAL PATHOLOGY AND E-LEARNING:
      At present, e-learning systems are "stand-alone" solutions distributed on CD or
      via internet. A characteristic example is the Digital Lung Pathology CD
      (www.pathology-online.org), which includes about 60 different rare and common
      lung diseases and internet access to scientific library systems (PubMed), distant
      measurement servers (EuroQuant), or electronic journals (Elec J Pathol Histol). A
      new and complete data base based upon this CD will combine e-learning and e
      teaching with the actual workflow in a virtual pathology institution (mode a).
      The technological problems are solved and do not depend upon technical
      constraints such as slide scanning systems. PERSPECTIVES: Telepathology serves as
      promotor for a new landscape in diagnostic pathology, the so-called virtual
      pathology institution. Industrial and scientific efforts will probably allow an
      implementation of this technique within the next two years.

PMID- 15718596
TI  - New trends in diabetes management: mobile telemedicine closed-loop system.
AB  - The rapid growth and development of information technologies over recent years,
      in the areas of mobile and wireless technologies is shaping a new technological
      scenario of telemedicine in diabetes. This telemedicine scenario can play an
      important role for further acceptance by diabetic patients of the existing
      continuous glucose monitoring systems and insulin pumps with the final goal of
      improving current therapeutic procedures. This paper describes a Personal Smart
      Assistant integrated in a multi-access telemedicine architecture for the
      implementation of a mobile telemedicine closed-loop system for diabetes
      management. The system is being evaluated within the European Union project named
      INCA ("Intelligent Control Assistant for Diabetes").

PMID- 15718597
TI  - Migration aspects of telemedical software architectures.
AB  - Many existing medical systems are good candidates for improvement via incremental
      migration. Incremental software improvement is, however, much more difficult if
      the system consists of independent functional modules built with different
      technologies. The goal of this paper is to present architecture migration aspects
      of contemporary telemedical systems. The paper discusses two approaches: the
      Software Architecture Analysis Method, and the Architecture Tradeoff Analysis
      Method in the context of migration of the medical teleconsultation system Konsul.
      The system, designed and implemented under KCT activity, is being successfully
      employed in day-to-day activities at the John Paul II Hospital in Krakow despite
      many existing drawbacks in its internal architecture. The paper presents the SAAM
      method of analysis of legacy systems. Two architectures are proposed as a result
      of this analysis - one based on the migration of the existing architecture, the
      other built according to the state-of-the-art Service Oriented Architecture.
      Konsul II, implementing the migration approach, has already been developed
      whereas Konsul III is in the design phase. The paper concludes with remarks about
      migration of telemedical systems.

PMID- 15718598
TI  - The impact of teleconsultations at a referential centre on the management of
      pulmonary patients.
AB  - Teleconsultation services at referential centres are an important area of
      telemedicine development. The implementation of such scenarios brings high-level
      competencies to peripheral hospitals through telecommunication links. Pulmonary
      teleconsultations were one of the key aspects of Krakow Centre of Telemedicine
      (KCT) activities conducted in 2002-2003. The role of the referential centre for
      respiratory medicine was played by the Division of Interventional Pulmonology,
      Jagiellonian University Medical College. Peripheral centres were pulmonary wards
      situated in local hospitals or policlinics located 20-80 km from Krakow. These
      hospitals were equipped with PC-based telemedical workstations and ISDN lines
      (256 kbps). Dedicated software (Telenegatoscope) was used for real-time
      discussions among physicians on medical images (X-rays, CTs) sent from peripheral
      centres to the referential centre. Images inserted in light boxes were cropped at
      peripheral centres with a high-resolution digital camera. During the pilot phase,
      about 40 pulmonary patients were referred via telemedical links to the University
      Hospital. The frequency of soliciting a second opinion at the referential centre
      was analyzed for each main type of disease. Top positions are currently occupied
      by diagnoses of lung cancer, pleural fluid of unknown origin, asbestosis and
      tuberculosis. About 70% of the patients referred for virtual consultation were
      admitted for further diagnostics and treatment in an ambulatory or inpatient mode
      at the Division of Interventional Pulmonology. The review of teleconsultations
      results indicates that teleconferencing contacts, even if conducted through
      relatively limited bandwidth, may bring considerable benefits to patients
      requiring complex diagnostic and sophisticated, procedures available at the
      referential university hospital.

PMID- 15718599
TI  - Web access to data in a mobile ECG monitoring system.
AB  - Cardiovascular diseases and, in particular, diseases related to arrhythmias are a
      problem that affects a significant percentage of the population, being one of the
      major causes of death in Europe. New advances in the fields of PDAs, mobile
      phones, wireless communications and vital parameter sensors have permitted the
      development of revolutionary medical monitoring systems, which strikingly improve
      the lifestyle of patients. However, not all those monitoring systems provide
      patients with real assistance - anywhere and at any time. We have developed a
      system that goes a step further than the previous approaches, being designed to
      capture, record and, as a distinctive feature, locally analyze the ECG signals in
      a PDA carried by the patient. In that sense, the system has a decision support
      module based on decision tree methods that can detect, with high precision, any
      arrhythmias that the user may be suffering. Alarms can then be activated in time
      to alert a medical center in order to provide the proper medical assistance. One
      of our aims when building the system has been to optimize limited and expensive
      resources like PDA memory size and wireless communication costs. Moreover,
      accessibility is also an important feature of the system that has been achieved
      by the development of web services to query the data computed in the PDA. In this
      way, authorized personnel (physicians and relatives) can easily obtain access to
      that data.

PMID- 15718600
TI  - Remote continuous cardiac arrhythmias detection and monitoring.
AB  - The current techniques used to diagnose cardiac arrhythmias such as Holter, Rtest
      and telemetry systems are partially efficient because they are limited either in
      time or in space. In this paper, a platform dedicated to the real-time remote
      continuous cardiac arrhythmias detection and monitoring is proposed. Such a
      platform allows to improve the accuracy and the efficiency of the diagnostic of
      ventricular tachycardia among the high-risk patients and enables the implantation
      of ICD to prevent sudden death. The new method allows the patient to lead a
      normal life while being remotely monitored in real-time by an ambulatory wireless
      ECG sensor. When a cardiac arrhythmia is detected a message including a sequence
      of ECG signals and the patient's images (indoors only) is sent to a remote
      surveillance server. According to the gravity of the symptom, the cardiologist
      can intervene in real time or later. The system has been evaluated on some ten
      patients with regard to heartbeat and cardiac rhythm disturbance. The real-time
      results are similar to those offered by HP telemetry systems.

PMID- 15718601
TI  - Cardiological telemonitoring in rehabilitation and sports medicine.
AB  - The paper presents the development results of teleconsultative cardiology systems
      and their application in rehabilitation and sport medicine. The first
      teleconsultative cardiology (TELECARD) system was developed for outpatient
      departments in the city of Kaunas, using Internet links. It was based on the
      CompCardioSignal terminal. One branch of the TELECARD system with a mobile
      CompCardioSignal terminal was used for functional state evaluation of Lithuanian
      sportsmen during the 2000 Sydney Olympic Games. The examined results have shown
      that every sportsman responded differently to acclimatization and the TELECARD
      system provided support to physicians and coaches for making optimal decisions
      regarding the sportsmen's adaptation and other situations. The final telemetry
      system was used for rower monitoring. It was based on the new CompCardioSignal
      terminal with three EASI ECG leads and synchronously recorded motion signals for
      evaluation of human reaction to physical load. The developed telemonitoring
      systems were a useful tool for evaluation of human reaction to physical load in
      rehabilitation and sports activities.

PMID- 15718602
TI  - Development of methods for monitoring of electrocardiograms, impedance
      cardiograms and seismocardiograms.
AB  - Cardiovascular diseases remain the main cause of morbidity and mortality in
      Lithuania, and early detection of those diseases is one of opportunities to
      reduce this problem. Usage of information technologies including clinical
      decision support systems, telemedicine networks and computer analysis of cardiac
      signals, can serve this purpose. Therefore, the presented paper deals with
      development of a system for the analysis of 12-lead electrocardiograms (ECG),
      impedance cardiograms (ICG) and seismocardiograms (SCG) in the aim to use it in a
      wider cardiologic teleconsultative system. Such a complex set of signals makes it
      possible to monitor the electric (ECG), hemodynamic (ICG) and mechanical (SCG)
      properties of cardiac activity. The hardware for synchronous recording of 12-lead
      ECG, ICG and SCG as well as the software containing programs for signal input,
      recognition, measurement, analysis and data transmission has been developed.

PMID- 15718603
TI  - Relationships between healthcare and research records.
AB  - The ultimate end-point of healthcare and health-related life sciences, more or
      less as regulatory idea, is the prevention and cure of diseases, considering the
      fate of individual patients as well as the challenge of providing sufficient care
      for all. However, all undertakings stand under the "proviso of rightness of
      action". The movement of evidence-based medicine has triggered a renaissance of
      systematic self-assurance of best practise. The systematic utilization of
      healthcare records and research study recordings in an inter-linked manner
      provides a better enabling environment to improve evidence. Good e-health must
      contribute to accumulate inter-generation clinical experience. Qualified research
      should ensure methodological strictness via gold standards like controlled,
      randomised and masked trials. Building information systems for e-health as well
      as for e-science bears as a special focus the mutual cross-fertilization of these
      application domains. Analysing a variety of building blocks shows that both areas
      can benefit from generic solution pattern, keeping in mind that each domain has
      distinguished knowledge realms. Generic patterns as well as distinguished special
      features are illustrated by analysing state of the art solutions plus some
      experimental approaches, as there are: the generic part of the HL7 V3 RIM, the
      RCRIM work, laboratory information handling, vital sign standardization efforts,
      like ECG information models.Finally, the precision of the usage of the ubiquitous
      term "metadata" is taken as example of an open issue.

PMID- 15718604
TI  - Integrating electronic guidelines into the diagnostic cycle.
AB  - Clinical guidelines have been used for diagnostic and treatment purposes, and
      lately much of this information has become available in electronic formats. In
      Norway a medical electronic handbook has been developed [1] to give support for
      the physician, deciding upon diagnoses and treatment. This electronic handbook is
      now widely used, but not in a systematic fashion - due to lack of user
      friendliness. The lack of integration with EPR systems and, more importantly, the
      lack of integration with the working process, are additional obstacles. In order
      to improve the usability of the electronic handbook, we have developed a
      prototype where the commercially-available handbook is tightly integrated with
      the EPR system and where the EPR system is based on a problem-based approach. The
      prototype is focused on providing support to the diagnostic process, treatment
      planning, documentation and pointers to extended knowledge support. The
      integration of knowledge support and the EPR system was based on a semantic model
      representation in the middleware and an XML-based representation of the knowledge
      content within a SQL database. In addition to clinical guidelines, the ICPC-2[2]
      codes and their inclusion and exclusion criteria are used to support the
      diagnostic task.

PMID- 15718605
TI  - Presentation of medical guidelines on a computer.
AB  - Free-text forms of medical guidelines that are used in medical care are often
      cumbersome and difficult to memorize. Therefore a system that is able to present
      guidelines in a user-friendly manner has been designed. Guidelines are at first
      formalized by means of the popular GLIF3 model. Subsequently, the GLIF3 model is
      coded in XML. The system uses patient data and an XML-coded GLIF3 model graph
      evaluating the conditions of decision steps. If some conditions cannot be
      evaluated, (due to the unavailability of required data items), the system stops
      and highlights a branch from the root of the decision tree to the final step.
      Then, the user can input missing data into the system so that the system can
      continue to provide visualization. Thus, the presentation of guidelines is data
      driven, making its use easier. The visualization system and the Electronic Health
      Record can be integrated in a system that can, during examination of a patient,
      suggest subsequent medical actions according to medical guidelines. Such a system
      has been designed and is now under development.

PMID- 15718606
TI  - Caseview: building the reference set.
AB  - There is a worldwide consensus for using the diagnosis related groups (DRG) when
      considering hospital activity. This tool leads to the production of tables of
      numbers (case mix), the interpretation of which is difficult. Therefore, methods
      aimed at facilitating this interpretation are needed. One of such methods is the
      case view, i.e. a graphical representation of the case mix. It reduces, in a way,
      each DRG to a "pixel", the set of the DRGs being an image (the case view). The
      reference set should be organized according to three criteria: medical/surgical,
      nosological and economic. This method can be used to answer theoretical questions
      or to visualize activity at the level of a hospital or at the level of a
      department. The purpose of this paper is to present important principles inherent
      in this graphic representation, both at the level of the method and at the level
      of the user.

PMID- 15718607
TI  - Caseview_HUN: easy DRG overview.
AB  - Several hospital management tools are currently used by the DRG financial system.
      Each case is classified into a DRG group, so it is necessary to know the
      distribution of hospital or departmental cases into DRG groups, and to follow the
      variances of this distribution. The DRG's properties include the income and
      expenses related to each case. There are differences in the profitability of the
      cases, depending on their DRG. It is important to know own expenses and the
      recuperated costs for every case. There are several systems for data collecting
      and analysis in hospitals, depending on existing hospital information systems and
      management. We can, however, be sure, that a DRG data collection system works in
      every department, because it is the basis of assessing income. The tool, which is
      shown in this article, facilitates an overview of the DRG, presenting the
      hospital's or other healthcare provider's own data. These services are supported
      by a platform-independent, accessible Internet application.

PMID- 15718608
TI  - Universal electronic health record MUDR.
AB  - One of the important research tasks of the European Centre for Medical
      Informatics, Statistics and Epidemiology - Cardio (EuroMISE Centre - Cardio) is
      the applied research in the field of electronic health record design including
      electronic medical guidelines and intelligent systems for data mining and
      decision support. The research in the field of data storage and data acquisition
      was inspired by several European projects and standards, mostly by the I4C and
      TripleC projects. Based on experience gathered during cooperation in the TripleC
      project we have proposed a description of a flexible information storage model.
      The motivation for this effort was the large variability of the set of collected
      features in different departments - including temporal variability. Therefore, a
      dynamically extensible and modifiable structure of items is needed. In our model
      we use two basic structures called the knowledge base and data files. The main
      function of the knowledge base is to express the hierarchy of collectable
      features - medical concepts, their characteristics and relations among them. The
      data files structure is used to store the patient's data itself. These two
      structures can be described using graph theory expressions. Based on this model,
      a three-layer system architecture named "Multimedia Distributed Record" (MUDR)
      has been proposed and implemented. During the implementation, modern technologies
      such as Web Services, SOAP and XML were used. For the practical usage of EHR
      MUDR, an intelligent application called MUDRc (MUDR Client) was created. It
      enables physicians to use EHR MUDR in a flexible way. During the development
      process, maximum emphasis was placed on user-friendliness and comfortable usage
      of this application. Several methods of data entry can be used: pre-defined
      forms, direct entry into the tree data structure of the EHR MUDR, or automatic
      unstructured free-text report parsing and data retrieval. The system enables fast
      and simple importing and exporting of data as well. The system integrates modern
      multimedia formats (X-ray photos, sonography and other pictures, video-sequences,
      audio records) as well as progressive methods of decision support systems
      realized by medical guidelines and other modules.

PMID- 15718609
TI  - MUDRLite - health record tailored to your particular needs.
AB  - Nowadays most hospitals use electronic health records as part of their hospital
      information systems. However, these systems are more suitable for hospital
      management than for physicians. The health record is not sufficiently structured;
      it includes a lot of free-text information, and the set of collected attributes
      is fixed and practically impossible to extend. Physicians, gathering information
      for the purpose of medical studies, often use varied proprietary solutions based
      on MS Access databases or MS Excel Sheets. The EuroMISE Centre - Cardio is
      developing an electronic health record (EHR) application called MUDRLite, which
      could easily fill the gap between existing EHRs. MUDRLite is the result of
      applied research in the field of EHR design, which is based on experience
      gathered during cooperation in the TripleC project. MUDRLite development is an
      extra branch in the MUDR (MUltimedia Distributed Record) development; it
      simplifies both the MUDR architecture and the MUDR data storage
      principles.MUDRLite itself is an empty body, which has to be filled in with an
      XML configuration file. This file completely describes the visual aspects and the
      behavior of the EHR application. It includes simple 4GL-like constructs written
      in the MUDRLite Language (MLL). This enables - using the event-oriented
      programming principles - to program various handling procedures for a range of
      actions, e.g. clicking a button fills a form with the result of an SQL statement.
      MUDRLite can be tailored to particular needs of any healthcare provider. This
      makes the MUDRLite application easy to use in specific environments. In the first
      instance, we are testing it at the Neurovascular Department of the Central
      Military Hospital in Prague.

PMID- 15718610
TI  - Access control mechanisms for distributed healthcare environments.
AB  - Today's IT-infrastructure provides more and more possibilities to share
      electronic patient data across several healthcare organizations and hospital
      departments. A strong requirement is sufficient data protection and security
      measures complying with the medical confidentiality and the data protection laws
      of each state or country like the European directive on data protection or the
      U.S. HIPAA privacy rule. In essence, the access control mechanisms and
      authorization structures of information systems must be able to realize the Need
      To-Access principle. This principle can be understood as a set of context
      sensitive access rules, regarding the patient's path across the organizations.
      The access control mechanisms of today's health information systems do not
      sufficiently satisfy this requirement, because information about participation of
      persons or organizations is not available within each system in a distributed
      environment. This problem could be solved by appropriate security services. The
      CORBA healthcare domain standard contains such a service for obtaining
      authorization decisions and administrating access decision policies (RAD). At the
      university hospital of Mainz we have developed an access control system (MACS),
      which includes the main functionality of the RAD specification and the access
      control logic that is needed for such a service. The basic design principles of
      our approach are role-based authorization, user rights with static and dynamic
      authorization data, context rules and the separation of three cooperating servers
      that provide up-to-date knowledge about users, roles and responsibilities. This
      paper introduces the design principles and the system design and critically
      evaluates the concepts based on practical experience.

PMID- 15718611
TI  - The performance of information technology in a cardiovascular system.
AB  - Our paper presents the results of a research study concerning the accuracy of the
      diagnosis and/or therapy for a cardiovascular patient. From the electronic
      patient records we have built a special database. The structure of this database
      offers possibilities for performing research studies on: cardiovascular
      pathology, risk factors action, medical treatment action, efficiency programs for
      primary and secondary prevention of diseases. The patient's data can be
      introduced from all intranet workstations of the cardiology department. The
      database structure is established to permit: optimal allocation of disk space,
      robust statistical analyses. The coding scheme can be explained as follows: if
      the information can have two or more values which exclude each other, the
      information is represented by a character; if the information can have more
      values which don't exclude each other, the field contains many characters
      representing possible values. Our paper shows that this database structure makes
      it possible to analyze every data piece that is stored. This system makes it
      possible to obtain a comprehensive summary of the cardiovascular population in
      real time by using standard reports and graphics, drill-down and roll-up on
      hierarchical dimensions, and analysis of temporal indicators. The database now
      contains information on 4000 patients undergoing effort tests as well as 2500
      patients in the recovery program, and the system is being tested for all
      registered patients. We hope that field tests can begin in the near future, in
      the framework of a national cardiovascular infrastructure program.

PMID- 15718612
TI  - Diagnosis and improvement of oral development of polish children with an impaired
      hearing system.
AB  - The experimental research presented in this paper concerning the evaluation and
      the development of oral abilities of Polish children with impaired hearing
      systems has been conducted with the use of two digital modules: the PCLX
      Laryngograph Processor and Nosality, connected to a PC computer. The aim of the
      research was the assessment, evaluation and determining positive changes in the
      level of oral development of Polish children with impaired hearing systems. The
      obtained results and following practical conclusions can serve as guidelines in
      clinical and logopedical applications in voice rehabilitation and communication
      development of groups of non-hearing children whose native language is not
      necessarily Polish.

PMID- 15718613
TI  - Artificial neural network in pharmacoeconomics.
AB  - Pharmacoeconomics research identifies, measures, and compares the costs
      (resources consumed) and consequences of medical products and services, where at
      least one of the compared alternatives is pharmacotherapy. Pharmacoeconomics has
      been designed to enable the decision maker to identify the preferred choice among
      existing alternatives. The decisions are often important for the patients' lives
      on the one hand, and for payers on the other (where the payer is understood as
      the institution responsible for financial resources allocation). One of the most
      commonly used types of pharmacoeconomic analysis is cost-effectiveness analysis.
      Two different alternatives can be compared using cost-effectiveness analysis if
      only their medical and clinical consequences could be measured in similar units
      (clinical or physical parameters). The aim of the project is to use an artificial
      neural network (ANN) for medical effect prediction, which could help in the
      extrapolation of pharmacoeconomic analysis' results. To depict neural data
      analysis tools, a database containing 100 non-small cell lung cancer (NSCLC)
      patients in non-operative IIIB and IV stage has been used. Each patient was
      described using 30 factors (i.e. sex, age, anticancer drugs dosage) and, as an
      output value, the expected survival time was established. The role of the ANN
      system was to predict the patient's survival time based on the above mentioned
      information. Binary values were tested as outcomes. Positive values (coded as 1)
      meant that patient survival time would be equal to or longer than 35 weeks.
      Negative values (coded as 0) meant that the patient survival time would be
      shorter than 35 weeks. Binary values were obtained using a threshold, which based
      on the mean survival time of patients derived from literature. Back-propagation
      as well as fuzzy-logic neural networks were applied. A 10-fold cross validation
      method was used to obtain the appropriate models. Final results were compared
      with the generic, logistic regression-based model. The best prediction score of
      the ANN model was 82%; higher than logistic regression prediction rate.

PMID- 15718614
TI  - Navigation systems based on registration of endoscopic and CT-derived virtual
      images for bronchofiberoscopic procedures.
AB  - Bronchofiberoscopy is an essential diagnostic procedure in patients with lung
      cancer. Sampling methods employed during endoscopy of the respiratory tract are
      performed with the aim of diagnosis confirmation and staging. Transbronchial
      needle aspiration may be used for evaluation of lymph nodes neighbouring with
      trachea and bronchi. Many efforts have been undertaken to increase the
      sensitivity of this procedure including the application of endobronchial
      ultrasonography. In recent years several research groups have proposed models of
      navigating systems to provide computer assistance during bronchoscopic
      interventions. Although they have used different techniques, their objective was
      the same - enabling tracking location and movement of bronchofiberoscope tip with
      reference to previously-acquired computed tomography (CT) images. Since a fiber
      optic bronchoscope is a rather long and flexible device, determination of its tip
      location is not an easy task. The adoption of optical tracking methods used in
      neurosurgery or laparoscopic surgery to endoscopy of the tracheobronchial tree is
      usually not possible. Another obstacle is related to the fact that
      bronchofiberoscopes usually have only one operational channel. This feature
      considerably limits the feasibility of navigation systems based on the use of
      small electromagnetic sensing devices or USG probes. The sources of positioning
      errors in such systems are respiratory movements and the lack of external
      referential coordinate system associated with the tracheobronchial tree.A
      promising option for development of a bronchoscopic guidance system is the
      application of image registration algorithms. Such an approach encompasses
      registration of endoscopic images to views derived from advanced imaging methods,
      e.g. CT. In the first step, reconstruction of a three-dimensional, endoluminal
      views is performed. Next, the position of the virtual camera in a CT-derived
      virtual model is determined using a complex multi-level image registering
      algorithm. This stage is the source of the greatest differences between proposed
      methods and a potential field for considerable improvements.This paper presents a
      review of recent as well as classical image registering methods used in
      navigation systems for bronchofiberoscopy. Details related to the selection of
      crucial elements of navigation systems based on image registering techniques,
      such as transformation, similarity criteria, matching and global optimization,
      are specified.

PMID- 15718615
TI  - Segmentation of human brain MR images using rule-based fuzzy logic inference.
AB  - The analysis of medical images for the purpose of computer-aided diagnosis and
      therapy planning includes the segmentation as a preliminary stage for the
      visualization or the quantification of such data. In this paper, we present a
      fuzzy segmentation system that is capable of segmenting magnetic resonance (MR)
      images of a human brain. The presented method consists of two main stages. The
      histogram analysis based on the S-function membership and Shannon's entropy
      function is the first step. In the final stage, pixel classification is performed
      using the rule-based fuzzy logic inference. After the segmentation is complete,
      attributes of different tissue classes may be determined (e.g., volumes), or the
      classes may be visualized as spatial objects. The implemented system provides
      many advanced 3D imaging tools, which enable visual exploration of segmented
      anatomical structures.

PMID- 15718616
TI  - Developing multimedia software and virtual reality worlds and their use in
      rehabilitation and psychology.
AB  - The multimedia and virtual reality projects performed at our laboratory during
      the last ten years can be grouped into the following groups: 1) tutorial and
      entertainment programs for handicapped children, 2) rehabilitation programs for
      stroke patients and patients with phobias. We have developed multimedia software
      for handicapped children with various impairments: partial vision, hearing
      difficulties, locomotive difficulties, mental retardation, dyslexia etc. In the
      present paper we show the advantages of using multimedia software to develop
      mental skills in handicapped people and deal with the special needs of
      handicapped children. For the rehabilitation of stroke patients we have developed
      a computer-controlled method, which enables - contrary to methods used
      internationally - not only the establishment of a diagnosis, but also measurement
      of therapy effectiveness: 1) it enables us to produce a database of patients,
      which contains not only their personal data but also test results, their drawings
      and audio recordings, 2) it is in itself an intensive therapeutic test and
      contains tutorial programs. We are currently collecting test results. We have
      also developed some virtual worlds for treating phobias: a virtual balcony and a
      ten-story building with an external glass elevator as well as an internal glass
      elevator in the virtual Atrium Hyatt hotel. We have developed a virtual
      environment for treating claustrophobia too: a closed lift and a room where the
      walls can move. For specific phobias (fear of travelling) we have modelled the
      underground railway system in Budapest. For autistic children, we have developed
      virtual shopping software too. In this paper we present the advantages of virtual
      reality in the investigation, evaluation and treatment of perception, behaviour
      and neuropsychological disorders.

PMID- 15718617
TI  - Methods of bronchial tree reconstruction and camera distortion corrections for
      virtual endoscopic environments.
AB  - The use of three-dimensional visualization of anatomical structures in
      diagnostics and medical training is growing. The main components of virtual
      respiratory tract environments include reconstruction and simulation algorithms
      as well as correction methods of endoscope camera distortions in the case of
      virtually-enhanced navigation systems. Reconstruction methods rely usually on
      initial computer tomography (CT) image segmentation to trace contours of the
      tracheobronchial tree, which in turn are used in the visualization process. The
      main segmentation methods, including relatively simple approaches such as
      adaptive region-growing algorithms and more complex methods, e.g. hybrid
      algorithms based on region growing and mathematical morphology methods, are
      described in this paper. The errors and difficulties in the process of
      tracheobronchial tree reconstruction depend on the occurrence of distortions
      during CT image acquisition. They are usually related to the inability to exactly
      fulfil the sampling theorem's conditions. Other forms of distortions and noise
      such as additive white Gaussian noise, may also appear. The impact of these
      distortions on the segmentation and reconstruction may be diminished through the
      application of appropriately selected image prefiltering, which is also
      demonstrated in this paper. Methods of surface rendering (ray-casting, ray
      tracing techniques) and volume rendering will be shown, with special focus on
      aspects of hardware and software implementations. Finally, methods of camera
      distortions correction and simulation are presented. The mathematical camera
      models, the scope of their applications and types of distortions were have also
      been indicated.

PMID- 15718618
TI  - MEDIM - software system for content-based visual retrieval study in databases
      with medical images.
AB  - This paper presents the MEDIM software system created for the study of a number
      of methods used in the content-based visual retrieval, based on color
      characteristics. The problems studied with the help of this system are content
      based image query and extraction of color regions. The study of the implemented
      algorithms was conducted from the point of view of the retrieval quality and
      complexity, in different cases of transformation and quantization of color
      spaces, on a database with color medical images from the digestive apparatus
      sphere, collected with the help of an endoscope.

PMID- 15718619
TI  - Telelearning standards and their application in medical education.
AB  - Medial education, both on the graduate and postgraduate levels, has become a real
      challenge nowadays. The volume of information in medical sciences grows so
      rapidly that many health professionals experience essential problems in keeping
      track of the state of the art in this domain. e-learning offers important
      advantages to medical education continuation due to its universal availability
      and opportunity for implementation of flexible patterns of training. An important
      trace of medical education is developing practical skills. Some examples of
      standardization efforts include: the CEN/ISSS Workshop on Learning Technology
      (WSLT), the Advanced Learning Infrastructure Consortium (ALIC), Education Network
      Australia (EdNA) and PROmoting Multimedia access to Education and Training in
      European Society (PROMETEUS). Sun Microsystems' support (Sun ONE, iPlanetTM ) for
      many of the above-mentioned standards is described as well. Development of a
      medical digital video library with recordings of invasive procedures
      incorporating additional information and commentary may improve the efficiency of
      the training process in interventional medicine. A digital video library enabling
      access to videos of interventional procedures performed in the area of thoracic
      medicine may be a valuable element for developing practical skills. The library
      has been filled with video resources recorded at the Department of Interventional
      Pulmonology; it enhances training options for pulmonologists and thoracic
      surgeons. The main focus was put on demonstration of bronchofiberoscopic and
      videothoracoscopic procedures. The opportunity to browse video recordings of
      procedures performed in the specific field also considerably enhances the options
      for training in other medical specialties. In the era of growing health consumer
      awareness, patients are also perceived as the target audience for medical digital
      libraries. As a case study of Computer-Based Training systems, the Medical
      Digital Video Library is presented.

PMID- 15718620
TI  - Beyond wishful thinking; medical community presence on the web and challenges of
      pervasive healthcare.
AB  - Romanian healthcare is facing a number of challenges, from the growing general
      costs, through requests for better services, inadequate territorial coverage,
      medical errors and a growing incidence of chronic diseases, to the burden of debt
      toward the pharmaceutical industry. For the last 14 years decision factors have
      been searching for the magic formula in restructuring the healthcare sector.
      Eventually, the government has come to appreciate the benefits of IT solutions.
      Our paper presents recent advances in wireless technologies and their impact on
      healthcare, in parallel with the results of a study aimed to acknowledge the
      presence of the medical community on Romanian WWW and to evaluate the degree of
      accessibility for the general population. We have documented Web sites promoting
      health services, discussion forums for patients, online medical advice, medical
      image teleprocessing, health education, health research and documentation,
      pharmaceutical products, e-procurement, health portals, medical links, hospitals
      and other health units present on the Web. Initial results have shown that if the
      current trend in price decreases for mobile communications continues and if the
      government is able to provide funding for the communication infrastructure needed
      for pervasive healthcare systems together with the appropriate regulations and
      standards, this can be a long-term viable solution of the healthcare crisis.

PMID- 15718621
TI  - Implementing the HL7v3 standard in Croatian primary healthcare domain.
AB  - The mission of HL7 Inc. is to provide standards for the exchange, management and
      integration of data that supports clinical patient care and the management,
      delivery and evaluation of healthcare services. The scope of this work includes
      the specifications of flexible, cost-effective approaches, standards, guidelines,
      methodologies, and related services for interoperability between healthcare
      information systems. In the field of medical information technologies, HL7
      provides the world's most advanced information standards. Versions 1 and 2 of the
      HL7 standard have on the one hand solved many issues, but on the other
      demonstrated the size and complexity of the health information sharing problem.
      As the solution, a complete new methodology has been adopted, which is being
      encompassed in version 3 recommendations. This approach standardizes the
      Reference Information Model (RIM), which is the source of all domain models and
      message structures. Message design is now defined in detail, enabling
      interoperability between loosely-coupled systems that are designed by different
      vendors and deployed in various environments. At the start of the Primary
      Healthcare Information System project, we have decided to go directly to HL7v3.
      Implementing the HL7v3 standard in healthcare applications represents a
      challenging task. By using standardized refinement and localization methods we
      were able to define information models for Croatian primary healthcare domain.
      The scope of our work includes clinical, financial and administrative data
      management, where in some cases we were compelled to introduce new HL7v3
      compliant models. All of the HL7v3 transactions are digitally signed, using the
      W3C XML Digital Signature standard.

PMID- 15718622
TI  - Development of teleconsultations systems for e-health.
AB  - Two prototype telemedicine systems have been developed: 1) a wireless system for
      status assessment of cardiology patients (WSCP), 2) a system for medical image
      management and teleconsultations (IMTS). The former system enables the patient to
      record an ECG on a personal digital assistant (PDA), view it and send it via a
      wireless connection. The doctor on duty is then able to view the received ECG and
      make appropriate decisions, also to apply for consultation by sending the
      received ECG to the PDA of a cardiology expert. The system logs all performed
      operations. The hardware used in the system consists of personal computers (PCs),
      PDAs, analog-digital converters, ECG sensors and GPRS modems. Software consists
      of programs for patients, doctors on duty, cardiology experts and administration,
      along with a central database. The second system is intended to be used by
      professional doctors for management of collected images and for teleconsultations
      via videoconferencing in order to obtain a second opinion. The system provides an
      integrated environment eliminating the need to jump between many applications. By
      using the system, doctors are able to acquire images from analog and digital
      cameras, process and enhance them, as well as upload them to local or remote
      databases. Doctors are also able to design custom database forms. The
      teleconsultation part of the system supports video and audio over ISDN and TCP
      IP, using both a hardware codec (Zydacron Z360) and a software codec (based on MS
      Netmeeting). Images are sent from one client to another using the standard
      protocol T.120. Images become synchronized immediately upon reception by another
      client.

PMID- 15718625
TI  - Health in the information and knowledge economy age--a European perspective.
AB  - The health sector today faces great challenges. Health is an information
      intensive sector where Information and Communication Technologies (ICTs) could
      significantly contribute to efficiency and productivity gains. European Union is
      looking at the different facets of eHealth and mainly at the following three: a)
      Research and development, in particular to support the development of several
      regional health information networks, telemedicine services, and personal health
      systems for patients and citizens. b) Regulatory framework and standardisation,
      which ensure competition, interoperability and, at the same time, the
      confidentiality of personal data. c) Promotion of eHealth best practices through
      various eEurope 2002 and 2005 initiatives. After the pharmaceutical and radiology
      industry, eHealth is now the third industrial pillar for health. This emerging
      sector forms the backbone for the reengineering of health systems. It actually
      improves the access to and quality of care and places citizens at the very centre
      of its concern.

PMID- 15718626
TI  - New concepts and technologies in home care and ambulatory monitoring.
AB  - The world is becoming more and more health conscious. Society, health policy and
      patients' needs are all changing dramatically. The challenges society is
      currently facing are related to the increase in the aging population, changes in
      lifestyle, the need for healthcare cost containment and the need for improvement
      and monitoring of healthcare quality. The emphasis is put on prevention rather
      than on treatment. In addition, patients and health consumers are waiting for non
      invasive or minimally-invasive diagnosis and treatment methods, for home care,
      short stays in hospital, enhancement of rehabilitation, information and
      involvement in their own treatment. Progress in science and technology offers,
      today, miniaturization, speed, intelligence, sophistication and new materials at
      lower cost. In this new landscape, microtechnologies, information technologies
      and telecommunications are key factors. Telemedicine has also evolved. Used
      initially to exchange patients' files, radiographic data and other information
      between health providers, today telemedicine contributes to new trends in
      "hospital extension" through all-day monitoring of vital signs, professional
      activities, entertainment and home-based activities. The new possibilities for
      home care and ambulatory monitoring are provided at 4 levels: a) Microsensors.
      Microtechnologies offer the possibility of small size, but also of intelligent,
      active devices, working with low energy, wireless and non-invasive or minimally
      invasive; b) Wrist devices are particularly user friendly and combine sensors,
      circuits, supply, display and wireless transmission in a single box, very
      convenient for common physical activities; c) Health smart clothes make contact
      with 90 % of the skin and offer many possibilities for the location of sensors.
      These sensors have to be thin, flexible and compatible with textiles, or made
      using textile technologies, such as new fibers with specific (mechanical,
      electrical and optical) properties; d) Health smart homes. The aim of this method
      is to improve the patient's living conditions and to avoid the cost of long
      hospitalization. "Exosensors" are used for measurement of the activity and
      behavior of the patient. The field of applications is very large, e.g. continuous
      monitoring of elderly populations, professional and military activities, athletes
      performance and condition, and people with disabilities. This new healthcare
      approach has to take into account lifestyle for improving prevention. For the
      patient to be more and more involved in his/her own therapy, new responsibilities
      and ethics have to be defined. A "societal health education" has to be provided
      to physicians and to patients to get all the benefits of this new context.

PMID- 15718627
TI  - MyHeart: fighting cardiovascular disease by preventive lifestyle and early
      diagnosis.
AB  - MyHeart is an integrated project of the 6th framework programme for research and
      development of the European Commission under Philips Research Aachen leadership
      for fighting Cardiovascular Diseases (CVD) by prevention and early diagnosis. The
      major goal of the project is to create business options using smart electronic
      systems and appropriate services that empower the users to take control of their
      own health status. MyHeart addresses a wide variety of applications in the
      cardiovascular disease space and intends to develop lifelong solutions for
      healthy people, at risk population as well for chronically ill patients.

PMID- 15718628
TI  - Health0: a new health and lifestyle management paradigm.
AB  - The paper describes Health0: an innovative healthcare and lifestyle management
      wearable system that aims to bring an individual focused approach to healthcare.
      A modular architecture is proposed that combines a Linux-based PDA with a
      distributed wireless sensor-network and innovative bandage-sized (2.5 cm2) sensor
      hardware. Real-world scenarios that can use the Health0 system are discussed.

PMID- 15718629
TI  - How wearable technologies will impact the future of health care.
AB  - After four hundred years of delivering health care in hospitals, industrialized
      countries are now shifting towards treating patients at the "point of need". This
      trend will likely accelerate demand for, and adoption of, wearable computing and
      smart fabric and interactive textile (SFIT) solutions. These healthcare solutions
      will be designed to provide real-time vital and diagnostic information to health
      care providers, patients, and related stakeholders in such a manner as to improve
      quality of care, reduce the cost of care, and allow patients greater control over
      their own health. The current market size for wearable computing and SFIT
      solutions is modest; however, the future outlook is extremely strong. Venture
      Development Corporation, a technology market research and strategy firm, was
      founded in 1971. Over the years, VDC has developed and implemented a unique and
      highly successful methodology for forecasting and analyzing highly dynamic
      technology markets. VDC has extensive experience in providing multi-client and
      proprietary analysis in the electronic components, advanced materials, and mobile
      computing markets.

PMID- 15718631
TI  - I-wear for health care and wellness--state of the art and future possibilities.
AB  - The background of the development of i-wear for health care and wellness are two
      actual trends: The wellness trend with its expectation to stay fit and healthy
      and the increasing life expectancy of the Europeans and the challenges, which are
      resulting thereof for the medicine and the technology that goes with it. Already
      in 2040 the amount of people over 60 years in Europe will amount to 40% of the
      entire population [1,2]. In recent years the co-operation of physicians,
      biologists, physiologists, engineers for electronics and information technologies
      and textile scientists has produced a multitude of innovative applications for
      textiles, especially in the medical and wellness field. This presentation will
      cover the state of the art and some future aspects of textile-integrated
      solutions for health and wellness services, with intelligent application forms or
      integrated electronics (i-wear), which are an increasing market for textiles.

PMID- 15718630
TI  - Optimizing workflow and knowledge in healthcare through innovation.
AB  - People's desire is to stay healthy during the entire course of their live.
      Innovations in medicine in care and technology have always contributed
      significantly to meet this desire as close as possible. Today, healthcare systems
      are faced with huge additional challenges. The focus of nearly every healthcare
      debate is on costs. But is this debate target-oriented and does it support the
      struggle for further enhancing the quality of care? The implementation of IT
      assisted workflow and knowledge supporting tools throughout the entire healthcare
      process--prevention to cure--leads to care which would be much more focused on
      people's needs and efficiency. The information gained from monitoring and
      wearable devices has to be included to these tools for delivering comprehensive
      patient information to the point of care. Then the puzzle of the different
      components in healthcare linked by IT will be complete, and the care process
      could be continuously optimized in an efficient way.

PMID- 15718632
TI  - Research in intelligent biomedical clothing vs. realities in the European textile
      business.
AB  - In order to make intelligent biomedical clothing a market reality, a critical
      mass of scientific, technical and industrial capacities from various disciplines
      and industries must be successfully brought together. The textiles and clothing
      sector, i.e. the industry that transform natural or man-made fibres into yarns
      then with a myriad of processing options into complex tissues and finally into
      clothing, is undoubtedly a crucial element in such development. With Europe
      disposing of the world's most diverse, productive and innovative textiles and
      clothing industry, in addition to relevant expertise and resources in other
      scientific disciplines and industrial sectors, it could play a leading role in
      the advancement of the concept of intelligent biomedical clothing. In this
      process, a great number of challenges--firstly scientific and technical in nature
      -still need to be overcome and support from public funding programmes could
      constitute the necessary trigger for research and industrial efforts to be
      seriously undertaken. In view of the great benefits of such new products for the
      individual consumer, national health care systems and the society as a whole, a
      concerted effort in private-public partnership seems merited.

PMID- 15718633
TI  - Current and future R&D activities of the EC-IST programme in eHealth.
AB  - The EU support to R&D in eHealth over the last few years has addressed citizens,
      patients and health professionals needs in their activities. The societal
      challenges based on the principle of citizen-centred care have found solutions in
      the many projects financed through the IST programme. Major paradigm shifts have
      emerged e.g. from "hospital centred healthcare" to "patient/citizen centred
      health" and from "treatment" to "prevention". Information technologies became one
      of the major driving forces for healthcare evolution, receiving acceptance by an
      increasing number of health professionals. In addition, a new industrial sector
      was clearly identified; the "Health Telematics Industry". This paper present the
      main research and development activities carried out in eHealth during the 5th
      R&D Framework Programme and the future research and development activities in the
      6th R&D Framework Programme.

PMID- 15718634
TI  - Interactive textiles for warrior systems applications.
AB  - The purpose of this paper is to briefly summarize the basis of the U.S. Army's
      interest in Interactive Textiles and to describe some of the salient needs in the
      area of healthcare and E-Textiles and finally to indicate the current and near
      term market for interactive textile solutions. The basis of current Army, indeed
      DoD interest in Interactive Textiles including E-Textiles is found in the concept
      of Network-Centric Warfare. The individual soldier in this concept is often at
      the hub of a vast information network than shares information across platforms
      such as vehicles and aircraft as well as across echelongs of command from the
      font line to the rearmost command and control centers. In order to realize the
      advantages of such a war fighting concept, E-Textiles are required in a number of
      areas including soldier's uniforms, tentage and airdrop systems. With respect to
      healthcare, the Army's interest in E-Textile solutions lie in the areas of human
      performance monitoring (broadly defined to include physiological states such as
      blood pressure and hydration as well as the more difficult to measure states of
      attentiveness and cognitive functioning), wound detection and treatment, energy
      harvesting and flexible displays.

PMID- 15718635
TI  - Challenges of ambulatory physiological sensing.
AB  - Applications for ambulatory monitoring span the spectrum from fitness
      optimization to cardiac defibrillation. This range of applications is associated
      with a corresponding range of required detection accuracies and a range of
      inconvenience and discomfort that wearers are willing to tolerate. This paper
      describes a selection of physiological sensors and how they might best be worn in
      the unconstrained ambulatory environment to provide the most robust measurements
      and the greatest comfort to the wearer. Using wireless mobile computing devices,
      it will be possible to record, analyze and respond to changes in the wearers'
      physiological signals in real time using these sensors.

PMID- 15718636
TI  - Driver monitoring--new challenges for smart sensor-based systems.
AB  - Decreased vigilance and fatigue are major factors accounting for driver error.
      Moreover, it is one of the most common causes of traffic accidents. The
      development and integration of non invasive systems to detect driver fatigue in
      real time is a challenging task for the near future. Smart systems promise new
      approaches to sensor development, signal processing and interpretation to asses
      the evolution of the physiological state of the driver. At the same time,
      however, driver monitoring should be realistic in terms of automotive
      constraints, price and robustness. Can smart materials meet those requirements?
      Issues involved in driver monitoring will be discussed and an overview of the
      demands placed on smart materials by the automotive environment will be given.

PMID- 15718637
TI  - Market research on garment-based "wearables" and biophysical monitoring and a new
      monitoring method.
AB  - Technology advancements are foremost on the minds of scientists and developers
      who are working to overcome the many hurdles associated with bringing consumers
      the enhanced benefits associated with next generation wearable health systems.
      Often the technology work takes a front seat to the basic requirements of
      traditional consumer apparel. The choices of what consumers elect to place and
      carry on their body can be practical, logical, emotional and sometimes seemingly
      random. By providing insights and data to support the claims, developers of
      wearable health systems of the future will be able improve their chance of
      consumer adoption and continued use by gaining a clearer picture of the people
      that will be wearing the systems. Results from 5 different consumer research
      studies are presented, examining consumer buying patterns, gender differences,
      regional differences, their receptivity to health benefits delivered via clothing
      and what they want from technology enhanced clothing. Market research related to
      biophysical monitoring utilizing smart fabrics or interactive textiles show a
      critical level of commercial activity. Medical applications focused on the aged,
      infant and critical patient care are taking the lead. This paper presents a look
      at the biophysical monitoring market and discusses new materials useful in
      garment systems and the challenges remaining for their development and
      integration with textiles. A new method of non-invasive monitoring of periodic
      activity is discussed.

PMID- 15718638
TI  - New paradigms in telemedicine: ambient intelligence, wearable, pervasive and
      personalized.
AB  - After decades of development of information systems dedicated to health
      professionals, there is an increasing demand for personalized and non-hospital
      based care. An especially critical domain is cardiology: almost two third of
      cardiac deaths occur out of hospital, and victims do not survive long enough to
      benefit from in-hospital treatments. We need to reduce the time before treatment.
      But symptoms are often interpreted wrongly. The only immediate diagnostic tool to
      assess the possibility of a cardiac event is the electrocardiogram (ECG). Event
      and transtelephonic ECG recorders are used to improve decision making but require
      setting up new infrastructures. The European EPI-MEDICS project has developed an
      intelligent Personal ECG Monitor (PEM) for the early detection of cardiac events.
      The PEM embeds advanced decision making techniques, generates different alarm
      levels and forwards alarm messages to the relevant care providers by means of new
      generation wireless communication. It is cost saving, involving care provider
      only if necessary and requiring no specific infrastructure. This solution is a
      typical example of pervasive computing and ambient intelligence that demonstrates
      how personalized, wearable, ubiquitous devices could improve healthcare.

PMID- 15718639
TI  - The LifeShirt: a multi-function ambulatory system monitoring health, disease, and
      medical intervention in the real world.
AB  - Despite advances made in health-related ambulatory monitoring, medical
      practitioners and researchers have remained seriously constrained in their
      ability to acquire concurrent assessments of multiple physiological systems, as
      well as patient reports of symptoms and well being in daily life: Almost all past
      and current applications have been limited to the registration of a single
      variable (e.g. the electrocardiogram or blood pressure), and this has resulted in
      incomplete information about other relevant physiological and environmental
      factors likely to contribute to disease or its amelioration. Monitoring of
      multiple physiological functions has been too complicated to achieve and has
      required special measurement devices that have been unavailable, too expensive,
      or too cumbersome to effectively employ. Concurrent assessment of pertinent
      information about patient activities during monitoring has remained difficult to
      accomplish, although such information is likely to be crucial for the
      interpretation of physiological findings and patients' perceptions of
      improvement. The LifeShirt (Vivometrics, Inc., Ventura, CA, U.S.A.) is a multi
      function ambulatory device capable of simultaneously monitoring several
      physiological signals and patient reports of symptoms and well being. The
      LifeShirt system is an extensible data acquisition and processing platform
      consisting of a garment, a data recorder, and PC-based analysis software. Sensors
      in the LifeShirt garment continuously monitor respiration, the electrocardiogram,
      activity and posture. Other functions are easily plugged into the system,
      including pulse oximetry, EEG/ EOG measurement, blood pressure, temperature,
      capnometry and acoustic monitoring. Subjective patient data may also be entered
      into the LifeShirt recorder, and all data are encrypted and written to a flash
      memory card. Vivologic(TM) analysis software provides full-disclosure analysis
      and display of high-resolution waveforms and over 30 derived parameters; the
      software also produces summary reports for clinical diagnostic purposes. The
      LifeShirt has been rigorously tested for more than 38,000 hours in 90 studies
      with 1,750 subjects. The device has received all necessary regulatory approvals
      and is currently used in leading research institutions throughout the United
      States, Canada and Europe. Clinical applications include sleep diagnostics, heart
      disease, pulmonary disorders, cardiopulmonary rehabilitation, early hospital
      discharge and pre- and post-operative monitoring, human-factors in ergonomics and
      behavioral medicine.

PMID- 15718640
TI  - Body area network--a key infrastructure element for patient-centered
      telemedicine.
AB  - The Body Area Network (BAN) extends the range of existing wireless network
      technologies by an ultra-low range, ultra-low power network solution optimised
      for long-term or continuous healthcare applications. It enables wireless radio
      communication between several miniaturised, intelligent Body Sensor (or actor)
      Units (BSU) and a single Body Central Unit (BCU) worn at the human body. A
      separate wireless transmission link from the BCU to a network access point--using
      different technology--provides for online access to BAN components via usual
      network infrastructure. The BAN network protocol maintains dynamic ad-hoc network
      configuration scenarios and co-existence of multiple networks.BAN is expected to
      become a basic infrastructure element for electronic health services: By
      integrating patient-attached sensors and mobile actor units, distributed
      information and data processing systems, the range of medical workflow can be
      extended to include applications like wireless multi-parameter patient monitoring
      and therapy support. Beyond clinical use and professional disease management
      environments, private personal health assistance scenarios (without financial
      reimbursement by health agencies / insurance companies) enable a wide range of
      applications and services in future pervasive computing and networking
      environments.

PMID- 15718641
TI  - Contact centers, pervasive computing and telemedicine: a quality health care
      triangle.
AB  - The Citizen Health System (CHS) is a European Commission (CEC) funded project in
      the field of IST for Health. Its main goal is to develop a generic contact center
      which in its pilot stage can be used in the monitoring, treatment and management
      of chronically ill patients at home in Greece, Spain, and Germany. Such contact
      centers, using any type of communication technology, and providing timely and
      preventive prompting to the patients are envisaged in the future to evolve into
      well-being contact centers providing services to all citizens. In this paper, we
      present the structure of such a generic contact center and present its major
      achievements, and their impact to the quality of health delivery.

PMID- 15718642
TI  - Research and development of smart wearable health applications: the challenge
      ahead.
AB  - Continuous monitoring of physiological and physical parameters is necessary for
      the assessment and management of personal health status. It can significantly
      contribute to the reduction of healthcare cost by avoiding unnecessary
      hospitalisations and ensuring that those who need urgent care get it sooner. In
      conjunction with cost-effective telemedicine platforms, ubiquitous health
      monitoring can significantly contribute to the enhancement of disease prevention
      and early diagnosis, disease management, treatment and home rehabilitation.
      Latest developments in the area of micro and nanotechnologies, information
      processing and wireless communication offer, today, the possibility for minimally
      (or non) invasive biomedical measurement but also wearable sensing, processing
      and data communication. Although the systems are being developed to satisfy
      specific user needs, a number of common critical issues have to be tackled to
      achieve reliable and acceptable smart health wearable applications e.g.
      biomedical sensors, user interface, clinical validation, data security and
      confidentiality, scenarios of use, decision support, user acceptance and business
      models. Major technological achievements have been realised the last few years.
      Cutting edge development combining functional clothing and integrated electronics
      open a new research area and possibilities for body sensing and communicating
      health parameters. This paper reviews the current status of research and
      development on smart wearable health systems and applications and discusses the
      outstanding issues and future challenges.

PMID- 15718643
TI  - On-body diagnosis for wearable systems serving biomedical needs.
AB  - Early diagnosis as well as a healthy and preventive lifestyle can help slowing
      the onset of many health problems and save millions of lives per year. To achieve
      this objective, long-term monitoring of human vital signs are required to obtain
      knowledge on a person's health status. Continuous monitoring of vital signs is
      mandatory, but continuous transmission is expensive, in terms of financial costs
      as well as power consumption for battery operated portable systems. Clothing is
      like a second skin to us: intelligent biomedical clothes may make everyday life
      easier for people in poor health, helping them to lead productive lives, senior
      citizens and also for athletes. Clothing means fashion and fun: smart clothes
      will combine health problem prevention, entertainment, comfort, convenience and
      communication with fashion. This paper presents essential issues in wearable
      electronics, including interface with the garment, signal sensing and
      enhancement, signal processing of signal combination, on-body diagnosis and on
      body and distant communication. The paper reports on experience acquired through
      related projects running at the Swiss Center for Electronics and Microtechnology.

PMID- 15718644
TI  - Communication and interoperability for serial comparison in continuous health
      care--the new challenges.
AB  - The evolution of information technology and of telematics and increasing efforts
      to establish an electronic health record stimulate the development and
      introduction of new concepts in health care. However, compared to other
      application areas, e.g., tourism, banking, commerce etc. the use of information
      technology in health care is still of limited success. In hospitals as well in
      ambulatory medicine (General Practitioner systems) computers are often only used
      for administrative purposes. Fully operational Hospital Information Systems (HIS)
      are rare and often island solutions. The situation is somewhat better for
      department systems (DIS), e.g., where image analysis, processing of biochemical
      data or of biosignals is in the clinical focus. Even before we have solved the
      various problems in health care data processing and management within the
      "conventional" care institutions new challenges are coming up with concepts of
      telemedicine for assisted and non-assisted home care for patients with chronic
      diseases or people at high risk. The major challenges for provision of tele
      monitoring and alarming services are improvement of communication and
      interoperability of devices and care providers. A major obstacle in achieving
      such goals are lack of standards for devices as well for procedures and a lack of
      databases with information on "normal" variability of many medical parameters to
      be monitored by serial comparison in continuous medical care. Some of these
      aspects will be discussed in more detail.

PMID- 15718645
TI  - Wireless body area networks for healthcare: the MobiHealth project.
AB  - The forthcoming wide availability of high bandwidth public wireless networks will
      give rise to new mobile health care services. Towards this direction the
      MobiHealth project has developed and trialed a highly customisable vital signals'
      monitoring system based on a Body Area Network (BAN) and an m-health service
      platform utilizing next generation public wireless networks. The developed system
      allows the incorporation of diverse medical sensors via wireless connections, and
      the live transmission of the measured vital signals over public wireless networks
      to healthcare providers. Nine trials with different health care cases and patient
      groups in four different European countries have been conducted to test and
      verify the system, the service and the network infrastructure for its suitability
      and the restrictions it imposes to mobile health care applications.

PMID- 15718646
TI  - Development of electronic textiles for U.S. military protective clothing systems.
AB  - The focus of this paper is on the development of a wearable electronic network
      that provides data and power transport. A materials and manufacturing survey was
      conducted to determine the best performing and most durable materials to
      withstand the rigors of textile manufacturing and potential military use. Narrow
      woven technology was selected as the most appropriate manufacturing method. A
      working wearable narrow fabric version of the Universal Serial Bus (USB) was
      successfully developed and fabricated as well as related wearable connectors.
      Military products developed include a personal area network and body borne
      antenna.

PMID- 15718647
TI  - Wearable and implantable monitoring systems: 10 years experience at University of
      Ulster.
AB  - Over the past 10 years or more, NIBEC and, more recently, Sensor Technology and
      Devices Ltd have been at the forefront of developments in sensor-related
      technologies which underpin a wide range of monitoring systems presently
      commercialised by leading multinationals. Systems developed/ commercialised
      include astronaut-monitoring arrays, cardiac mapping harnesses, ECG electrodes,
      Telemedicine systems and implant sensor arrays. This paper presents the main
      developments in this area and discusses outstanding issues for future research.

PMID- 15718648
TI  - Artificial kinesthetic systems for telerehabilitation.
AB  - Artificial sensory motor systems are now under development in a truly wearable
      form using an innovative technology based on electroactive polymers. The
      integration of electroactive polymeric materials into wearable garments endorses
      them with strain sensing and mechanical actuation properties. The methodology
      underlying the design of haptic garments has necessarily to rely on knowledge of
      biological perceptual and motor processes which is, however, scattered and
      fragmented. Notwithstanding, the combined use of new polymeric electroactive
      materials in the form of fibers and fabrics with emerging concepts of biomimetic
      nature in sensor data analysis, pseudomuscular actuator control and biomechanical
      design may not only provide new avenues toward the realization of truly wearable
      kinesthetic and haptic interfaces, but also clues and instruments to better
      comprehend human manipulative and gestual functions. In this talk the conception,
      early stage implementation and preliminary testing of a fabric-based wearable
      interface endowed with spatially redundant strain sensing and distributed
      actuation are illustrated with reference to a wearable upper limb artificial
      kinesthesia system, intended to be used in telerehabilitation of post stroke
      patient.

PMID- 15718649
TI  - Implantable medical devices: current status and future developments within the
      healthy-aims project.
AB  - This paper describes the current situation concerning medical implants and
      suggests why the number of available devices is so limited. It then goes on to
      describe how a consortium was established from an EU network focussing
      specifically on Medical Devices. This consortium was successful in obtaining EU
      funding for the development of a range of medical implants that will help
      patients with specific disabilities relating to the nervous system, including
      deafness, blindness, lack of limb motion and urinary incontinence.

PMID- 15718650
TI  - The role of implantable sensors for management of heart failure.
AB  - Heart failure is a chronic disease with significant morbidity and mortality
      worldwide. Drugs such as ACE-inhibitors, beta-blockers and diuretics have helped
      control heart failure but the incidence of hospitalizations remains high.
      Rigorous continuous monitoring of patients and tailored therapy based on
      individual clinical and hemodynamic profile has been shown to limit the symptoms
      of heart failure. Self-monitoring or prescribed frequent in-clinic monitoring is
      logistically difficult and is fraught with patient non-compliance. Consequently,
      implantable sensors that can monitor patient's clinical status on a continuous
      basis are desirable. The disadvantage with an implantable sensor is obviously
      that the patient has to undergo an invasive procedure, which in itself has a
      certain risk, although minimal, associated with it. In addition, the risk of
      having an implantable device has to be weighed against the benefit of monitoring
      the patient on a continuous basis. The risk benefit question has been answered in
      part by the recent success of cardiac resynchronization therapy (CRT) in treating
      symptoms of heart failure. A recent study has performed a meta analysis on major
      heart failure trials conducted to date and concluded that CRT reduces mortality
      and morbidity. The CRT device is a specialized pacemaker with capabilities of
      continuous heart monitoring and embedded therapeutic decisions. A trend of heart
      rates offers significant insights into the progression of heart failure and
      patient status. In addition, using complex algorithms, several of the heart rate
      variability (HRV) parameters, identified in several studies for risk
      stratification and prognostication, can also be calculated. Furthermore, in
      recent devices based on heart rate intervals, autonomic balance (critical measure
      of progression of heart failure) can be estimated with sophisticated algorithms.
      Finally, technologies that can monitor patients' activity e.g. accelerometers,
      can be easily incorporated into the device. Such measures may be used to evaluate
      the efficacy of a new therapy or simply to provide patient status. Based on
      advances in technology, several patient clinical features can be monitored and
      trended over time. The measured metrics will help form a comprehensive and
      objective clinical profile of the patient that the physician can act upon.
      Prospective studies are needed to answer the efficacy of such diagnostic measures
      in management of heart failure.

PMID- 15718651
TI  - EvoCare: a new standard in tele-therapy.
AB  - The necessity for Integrated Care has been debated controversially and the
      influence of the legislator and the consequences for the medical device industry
      discussed sufficiently. In fact, the German health system has been suffering from
      a lot of problems like cost expansions, but only solutions and not discussions
      can bring a progress. EvoCare has established a new standard in tele-therapy in
      Germany. This has been possible because this system maps the clinical therapy
      process to tele-therapy (and not vice versa), it is extendable for virtually any
      medical field of application, and the user interface is kept so simple that
      people inexperienced with computers and even with motor deficits are able to use
      it. Accompanying the patients from the hospital to their homes, EvoCare allows
      for shorter hospital stays without loss in treatment quality and more intense
      training without increasing therapists' average work time per patient. The
      experiences that have already been made with the described system, especially in
      the area of neurological rehabilitation and orthopedic prevention, underline its
      advantages for all involved partners.

PMID- 15718652
TI  - e-Health and quality of life: the role of the Wearable Motherboard.
AB  - It is hard to place a price tag either on human life or on the quality of life.
      Technology is the key to enhancing the quality of life for everyone in the
      continuum of life from newborns to senior citizens--whether it is the safe
      delivery and care of undernourished premature babies, or extending the life of a
      senior citizen through exploratory treatments and procedures. Technology has the
      potential to rapidly transform healthcare and the practice of medicine by
      improving the quality and safety of patient care and increasing the efficiency of
      healthcare providers. Moreover, the healthcare industry must meet the challenge
      of balancing cost containment with maintenance of desired patient outcomes and
      this can be accomplished through the adoption of technology. Any technology that
      can minimize the loss of human life and/or enhance the quality of life has a
      value that is priceless. An overview of the key challenges facing the practice of
      medicine today is presented along with the need for technological solutions that
      can "prevent" problems. The paradigm of "e-Health" is discussed. Then, the
      development of the Wearable Motherboard as a "platform" for sensors and
      monitoring devices that can unobtrusively monitor the health and well-being of
      individuals (directly and/or remotely) is described. This is followed by a
      discussion of the applications and impact of this technology in the continuum of
      life--from preventing SIDS to facilitating independent living for senior
      citizens. Finally, the future advancements in the area of wearable, yet
      comfortable, systems that can continue the transformation of healthcare and e
      Health to i-Health (for interactive health)--all aimed at enhancing the quality
      of life for humans--are presented.

PMID- 15718653
TI  - Wearable system for vital signs monitoring.
AB  - A new concept in healthcare, aimed at providing continuous remote monitoring of
      user's vital signs, is emerging. An innovative system named WEALTHY is presented,
      where conducting and piezoresistive materials in the form of fiber and yarn are
      integrated and used as sensor and electrode elements. The simultaneous recording
      of vital signs allows parameter extrapolation and inter-signal elaboration that
      contribute to producing alert messages and synoptic patient tables. Cardiac
      patients in the rehabilitation phase can be continuously monitored during
      selected time intervals, such as during physical activity or occurrence of
      symptoms, to discover potential threats and generate appropriate alerts to the
      patient and/or to an emergency center. The core of the system sensing is a
      textile interface, in which the sensing components are elements of the fabric:
      the sensorized garment is comfortable like a common article of clothing and is
      made with knitting machines; furthermore, the position of the electrodes and
      sensors is fixed and the elasticity of the fabric allows a good fitting to the
      body. The system is provided with a portable electronic unit, where signals are
      acquired, elaborated and transmitted. A monitoring system allows extrapolation of
      a new physiological index and data flow coordination as well as alarm management
      and database creation.

PMID- 15718654
TI  - Telemonitoring of vital parameters with newly designed biomedical clothing.
AB  - The paper describes the development of biomedical clothing for ambulatory
      telemonitoring of human vital parameters. VTAM (Vetement de Tele-Assistance
      Medicale) presents a T-shirt made from textile with woven wires and incorporating
      four smooth dry ECG electrodes, a breath rate sensor, a shock/fall detector and
      two temperature sensors. The garment is equipped for the signal pre-computing and
      transmission through a miniature GSM/GPRS module kept on a belt together with the
      power supply. Three VTAM prototypes have been tested on persons in a normal state
      of health using a medical protocol to assess the biomedical data that include an
      ECG reading, a pneumogram, temperature and fall detection in mobile situations.

PMID- 15718655
TI  - Strain sensing fabric for hand posture and gesture monitoring.
AB  - Monitoring body kinematics and analyzing posture and gesture is an area of major
      importance in bioengineering and several other connected disciplines such as
      rehabilitation, sport medicine and ergonomics. Recent developments of new smart
      materials consent the realization of a new generation of garments with
      distributed sensors. What we present here is a sensing glove able to detect the
      posture and movements of the hand.

PMID- 15718656
TI  - Wearable textile biofeedback systems: are they too intelligent for the wearer?
AB  - The Intelligent Knee Sleeve is a device capable of providing immediate audible
      feedback to the wearer pertaining to knee flexion angle during human movement.
      The Intelligent Knee Sleeve was used in a landing training program to determine
      whether providing subjects with this form of feedback was able to effect a change
      in knee flexion angle during dynamic landing tasks. Preliminary results suggest
      that the feedback modality is effective in correcting landing technique. However,
      advancements in the Intelligent Knee Sleeve design would produce a more robust
      system leading to more effective biofeedback for the athlete.

PMID- 15718657
TI  - Potential applications of smart clothing solutions in health care and personal
      protection.
AB  - The rapid development in the fields of sensor and telecommunication technologies
      has created completely new possibilities also for the textile and clothing field.
      New smart textile and clothing systems can be developed by integrating sensors in
      the textile constructions. Application fields for these added-value products are
      e.g. protective clothing for extreme environments, garments for the health care
      sector, technical textiles, sport and leisure wear. Some products have already
      been introduced on the markets, but generally it can be stated that the
      development is only in its starting phase, and the expectations for the future
      are big. Many different aspects have to be considered in the development of the
      wearable technology products for the health care sector: medical problems and
      their diagnosis, sensor choice, data processing and telecommunication solutions,
      clothing requirements. A functional product can be achieved only if all aspects
      work together, and therefore experts from all fields should participate in the
      RTD projects. In the EC-funded project DE3002 Easytex clothing and textiles for
      disabled and elderly people were investigated. Some recommendations concerning
      durability, appearance, comfort, service and safety of products for different
      special user groups were defined, based on user questionnaires and seminars,
      general textile and clothing requirements and on laboratory test series."Clothing
      Area Network--Clan" is a research project aiming to develop a technical concept
      and technology needed in enabling both wired and wireless data and power transfer
      between different intelligent modules (user interfaces, sensors, CPU's, batteries
      etc.) integrated into a smart clothing system. Fire-fighters clothing system is
      chosen as the development platform, being a very challenging application from
      which the developed technology can be transferred to other protective clothing
      systems.

PMID- 15718658
TI  - Body motion capture for activity monitoring.
AB  - CEA-LETI has developed a 3D orientation tracker based on accelerometers and
      magnetometers. Owing to an efficient data fusion algorithm, the tracker provides
      accurate 3D orientation angles. The tracker is small enough to be used as a
      wearable device and therefore is an interesting tool for body motion capture.
      Investigations are being performed to analyse how activity of a person can be
      monitored from body motion measured with the tracker. In the domain of healthcare
      monitoring, many applications are envisaged such as rehabilitation with 3D body
      motion capture, elderly dependency evaluation, context acquisition for
      physiological monitoring.

PMID- 15718659
TI  - An e-textile system for motion analysis.
AB  - Electronic textiles (e-textiles) offer the promise of home health care devices
      that integrate seamlessly into the wearer's everyday lifestyle while providing a
      higher level of functionality than current devices. Existing gait analysis
      systems are cumbersome laboratory-based systems that, while providing valuable
      information, would be difficult or impossible to deploy in the home. Yet gait
      analysis systems offer the promise of preventing and/or mitigating the serious
      effects of falls in the elderly population. This paper proposes an e-textile
      solution to this problem along with a design approach for realizing a solution
      that is inexpensive and usable across the elderly population. Preliminary results
      are given to demonstrate the promise of the proposed system.

PMID- 15718660
TI  - New solutions for personalised health management: citizens' needs, healthcare
      changes, and market perspectives round table debate.
AB  - The aim with the round table was to give additional inputs and views to the
      specific technology oriented presentations focusing on issues dealing with the
      need, patients' view, the use and the business opportunities relating to wearable
      eHealth systems for personalised health management. Wearable eHealth systems for
      personalised health management are targeting citizens, patients at health risks
      and patients enrolled in open care or home care for monitoring, treatment or
      follow up. The developments so far show promises for these group categories, and
      in addition, could support developments in health care organisations and systems.
      However, the ethical issues and data privacy nature have to be seriously taken
      into account. The market is not yet developed, and this is the situation both in
      Europe and in the US. To be able to give the customers solid product information
      a standardised test bed for new equipment and services might speed up the market
      development. In the round table discussion it was highlighted that one has to
      differ between needs and demands. Needs are related to the prevalence of the
      diseases, the health risks, etc. Demands are more related to market developments
      and customers' willingness to pay for the new products and services. Further,
      technical interoperability was seen as a fundamental prerequisite for market
      acceptance. As wearable eHealth systems for personalised health management differ
      completely from traditional way of deliver healthcare, new reimbursement systems
      have to be developed and implemented.

PMID- 15718661
TI  - Smart fabrics: integrating fiber optic sensors and information networks.
AB  - "Smart Fabrics" are defined as fabrics capable of monitoring their own "health",
      and sensing environmental conditions. They consist of special type of sensors,
      signal processing, and communication network embedded into textile substrate.
      Available conventional sensors and networking systems are not fully
      technologically mature for such applications. New classes of miniature sensors,
      signal processing and networking systems are urgently needed for such
      application. Also, the methodology for integration into textile structures has to
      be developed. In this paper, the development of smart fabrics with embedded fiber
      optic systems is presented for applications in health monitoring and diagnostics.
      Successful development of such smart fabrics with embedded sensors and networks
      is mainly dependent on the development of the proper miniature sensors
      technology, and on the integration of these sensors into textile structures. The
      developed smart fabrics will be discussed and samples of the results will be
      presented.

PMID- 15718662
TI  - A feasibility study of yarns and fibers with annexed electronic functions: the
      ARIANNE project.
AB  - In this paper several issues concerning the development of fibers endowed with
      electronic functions will be presented and discussed. In particular, issues
      concerning materials, structures, electronic models and the mechanical
      constraints due to textile technologies will be detailed. All these aspects have
      been studied in the framework of the project ARIANNE, funded by the European
      Community during the V Frame Programme.

PMID- 15718663
TI  - Development of textile-based high-tech products: the new challenge.
AB  - The new generation of smart textiles is represented by fibers, yarns, fabrics and
      other resulting products that have special properties, regarding mechanical,
      chemical, electrical and thermal performances. These high-tech products, being
      able to respond to external stimuli through the integration of electronic
      components, phase change materials, shape memory materials or nano materials,
      enabled the development of different active and functional products. These
      products when combining the functions of medium, carrier and interface for micro
      systems applications represent the ideal connecting channel between humans and
      the environment. This is a field of innovation that broadened the scope of the
      traditional textile and apparel products to high-tech textiles, designed to meet
      specific needs, involving different technologies and produced according to
      required properties, like personal protection, safety, leisure or health wear.
      The development of smart wear is a new challenge for the textile and clothing
      industry: it has to develop products based not only on design, fashion and
      comfort concepts but also in terms of functions. Moreover these products must be
      easy to care and durable.

PMID- 15718664
TI  - Smart and hybrid materials: perspectives for their use in textile structures for
      better health care.
AB  - High tech materials such as Shape Memory Alloys can be effectively integrated in
      textiles, thus providing multifunctional garments with potential application to
      the health care industry or for simply improving the quality of life. The
      objective of the present paper is to describe the development of a novel hybrid
      fabric with embedded shape memory (Nitinol) wires, and the related clothing
      application with the capability of recovering any shape depending upon the
      environment and becoming superelastic. The use of these smart garments for
      biomedical applications will be illustrated, thus opening new perspectives for
      enhanced health care provision.

PMID- 15718665
TI  - Smart textiles.
AB  - After technical textiles and functional textiles, also smart textiles came into
      force a few years ago. The term 'smart textiles' covers a broad range. The
      application possibilities are only limited by our imagination and creativity. In
      this presentation, it is further explored what smart textiles precisely mean. In
      a second part, an analysis is made of the possibilities, the state of affairs and
      the needs for further research.

PMID- 15718668
TI  - Virtual university governance.
AB  - There is a need to establish collaboration alliances or partnerships if we are to
      provide global Health Informatics educatics education. Agreements need to make
      provision for the existing diversity between country educational systems as well
      as variations in funding, legislation and political systems and a number of other
      issues including intellectual property and copyright. Four virtual University
      governance models were identified, 1) evolution of existing universities, 2)
      newly created organisations collectively delivering one type of program eg MBA,
      3) a consortium of partners using a common portal and 4) a commercial enterprise.
      Collectively IMIA academic members need to be in a good position to respond to
      the global changes in higher education and minimise the risk of failure when
      establishing a virtual University to collectively deliver Health Informatics
      education. Others have undertaken a similar path in the past, some successful
      others not so, we need to learn from these experiences.

PMID- 15718669
TI  - Comparative educational systems.
AB  - During recent years Europe has been engaged in an educational reform that tends
      to change the whole educational system concerning higher education. The main
      issues of this reform are related to the free movement of labour and students
      across the member states. Hence, the need of comparative educational systems,
      levels, and degrees. The European Union and its executive bodies the European
      Council and European Commission have issued a series of declarations that are
      amalgamated in this chapter. The ideas behind these declarations formulate the
      framework of comparative educational systems that can have a significant impact
      on the global health informatics education.

PMID- 15718670
TI  - Academic standards, credit transfers and associated issues.
AB  - Various policies govern the way academic standards are managed and maintained.
      This includes organisational and program accreditation. Who decides what makes a
      program acceptable from a discipline and educational perspective? Should IMIA be
      developing accreditation guidelines for external program accreditation? Also the
      extent to which individual students are able to gain recognition for study
      undertaken elsewhere and thus reduce the length of the degree program undertaken
      varies by higher education provider. For example CQU provides credits based on
      study undertaken at the same level and where the content is similar as well as in
      line with overall program learning objectives for up to 50% of the total
      requirements. Internationally there are a number of governmental and not for
      profit private organisation providing an infrastructure to assist with the
      identification of legitimate educational certificates/degrees obtained overseas.
      In addition overseas skills recognition is undertaken by each University. This
      chapter examines these from a number of different international perspectives.

PMID- 15718671
TI  - Student and teacher exchanges--criteria for access.
AB  - Student and teacher exchanges between countries and within the domain of
      informatics to support health are considered. The availability of guidance
      appears to be institution-wide not country-specific. It is also not related to
      the discipline within which the exchange will occur. Concerns and issues are
      considered here in order for potential participants to prepare better for such
      exchanges. The observations made will be of interest to the administration of the
      organisations within which exchanges may occur. The investigation of this topic
      was delphic and pragmatic rather then exhaustive. The author bears no liability
      for situations that occur in specific locations.

PMID- 15718672
TI  - Gaining support from health disciplines and other stakeholders.
AB  - The Health industry employs health professionals from many disciplines all of
      whom need to have a basic understanding of health informatics principles and how
      information technologies may be used to improved health service delivery and
      patient/community/population health outcomes. This is not well understood by the
      workforce as a whole resulting in a low demand for health informatics education.
      Many health service managers and policy makers do not appreciate the power and
      potential usefulness of all health related information and the many technologies
      now available. This impacts on decisions regarding their acquisition,
      implementation and staff training/education support. This chapter includes
      recommended strategies on how to best overcome such knowledge deficits so that
      greater support for Health Informatics education is achieved.

PMID- 15718673
TI  - A health informatics educational framework.
AB  - There is a need to be able to define a Health Informatician by their graduate
      attributes. Futhermore global health informatics education that facilitates
      student mobility requires a common understanding of educational outcomes. An
      internationally agreed health informatics education framework will facilitate us
      to meet these needs. This chapter provides an overview of a considerable amount
      of work undertaken in a number of countries and by IMIA's health and medical
      informatics education working group. We need to make good use of these
      foundations as they clarify the various health informatics roles and functions
      together with their associated health informatics competency requirements. We are
      now in a good position to progress this work by developing a health informatics
      qualifications and educational framework. This is expected to assist educational
      providers with curriculum development.

PMID- 15718674
TI  - Curricula in medical informatics.
AB  - Education in medical informatics is needed not only for those who want to become
      specialist in this area but also for health professionals. Since students,
      depending on the program they are enlisted in, require different types of
      knowledge and skills in medical informatics, curricula should be adapted to those
      needs. The curriculum structure also depends on the expert level the students
      want to attain. This contribution presents the knowledge and skills levels for
      different groups of students and presents two examples of curricula.

PMID- 15718675
TI  - Competencies and credentialing: nursing informatics.
AB  - This paper provides an overview and description of the processes that address the
      competencies and credentialing of nurses in the field of nursing informatics
      (NI). It provides the highlights of the informatics competencies that were
      proposed as the NI field advanced. It also provides an overview of the ANCC
      nursing informatics credentialing process. It will also present the credentialing
      process of the HIMSS organization which offers several different certifications.
      And finally it will address the new process for the international certification
      entitled Nursing Informatics Competency Recognition Certificate. The Nursing
      Informatics Special Interest Group of the International Medical Informatics
      Association (IMIA/NI-SIG) approved this certificate at the general assembly
      meeting during NI'2003 in Rio de Janeiro, Brazil. The certification is based on a
      professional portfolio that demonstrates expertise in this field for nurses
      outside the USA and Canada.

PMID- 15718676
TI  - Health informatics needs regulation and registration to add value recognition.
AB  - Education is only one step towards being recognised as 'fit' to carry out an
      operational role in informatics to support health at any level. For many years
      there has been little real 'brand image'. Although significant bodies like IMIA
      and the BCS welcome a wide range of professionals, there is still confusion over
      what the discipline really means and does. In order to become a mature profession
      in the health domain, particularly in the UK, it is necessary to operate a
      registration process that recognises both qualification and competency, and the
      responsibility to keep skills and knowledge contemporary. This paper describes
      the steps taken to establish a registration and regulatory body to maintain high
      quality professionalism in operational care delivery, academic and commercial
      organisations in the health domain. The concepts described have resonance
      internationally.

PMID- 15718677
TI  - Educational standards -- terminologies used.
AB  - Efficient and effective delivery of health care requires accurate and relevant
      knowledge, patient-centred clinical data and medical information which is
      available to different actors and institutions in health care. Sharing data and
      knowledge means understanding the underlying concepts, terms, etc. Therefore a
      basic requirement in medical education is terminology, coding and classification.
      Vocabularies, data sets, schemes are to be used for medical documentation,
      medical statistics, analysis and system operation. Communication between
      heterogeneous environments will be possible when common terminologies etc. are
      available and used during system development. The following chapters give an
      overview on this important field of health telematics.

PMID- 15718678
TI  - Future trends in Health Informatics--theoretical and practical.
AB  - The Health Informatics field is becoming more challenging as the globalization of
      economy, the advancement of the technology as well as innovative breakthroughs
      are being incorporated in the discipline. In Europe as well as in other countries
      the funding into the research areas of this field is increasing. In this chapter,
      a brief overview of the field as well the trends of Health Informatics are
      discussed with respect to the new dimensions that the education of the health
      care professionals has to tackle in the foreseeable future.

PMID- 15718679
TI  - Current and future trends in teaching and learning.
AB  - The University of the 21st century provides learning experiences in a new way,
      using a variety of new technologies, online resources and new educational
      delivery methods to suit. Flexibility and the adoption of adult learning
      methodologies are key strategic directions adopted by many. This chapter provides
      an overview of student learning behaviours, learning styles and the relationship
      between these and various teaching technologies in terms of changing academic
      roles and workloads as well as the need for them to acquire new skills and
      knowledge to teach effectively in these new environments. The variety of teaching
      and learning options provided by technology allows education to be provided in an
      appropriate manner to a broader student demographic than ever before.

PMID- 15718680
TI  - Cognitive theories and the design of e-learning environments.
AB  - Cognitive development refers to a mental process by which knowledge is acquired,
      stored, and retrieved to solve problems. Therefore, cognitive developmental
      theories attempt to explain cognitive activities that contribute to students'
      intellectual development and their capacity to learn and solve problems.
      Cognitive developmental research has had a great impact on the constructivism
      movement in education and educational technology. In order to appreciate how
      cognitive developmental theories have contributed to the design, process and
      development of constructive e-learning environments, we shall first present
      Piaget's cognitive theory and derive an inquiry training model from it that will
      support a constructivism approach to teaching and learning. Second, we will
      discuss an example developed by NASA that used the Web as an appropriate
      instructional delivery medium to apply Piaget's cognitive theory to create e
      learning environments.

PMID- 15718681
TI  - Self directed and lifelong learning.
AB  - Given the many changes that occur in medicine, health care and information
      technologies we need to prepare all our students to engage in self directed and
      life long learning. There is considerable opportunity for self-directed and
      lifelong learning in health informatics bringing together students in exciting
      global learning environments, where they have much greater freedom and
      flexibility in their studies and potentially a wider variety of resources
      available to them. Self-directed learning focuses on the process by which adults
      take control of their own learning, in particular how they set their own learning
      goals, locate appropriate resources, decide on which learning methods to use and
      evaluate their progress. Lifelong learning happens in a variety of formal and
      informal settings building on both intentional and incidental learning
      experiences. In a lifelong learning situation the tutor must relinquish the role
      of expert and assume the role of facilitator, guiding learners to uncover their
      own knowledge. Against a back drop of rapid advances in technology which can be
      used to both deliver course materials and provide enhanced learning
      opportunities, this chapter outlines the pedagogic principles and practices which
      underpin self-directed and lifelong learning.

PMID- 15718682
TI  - Managing large online classes across multiple locations.
AB  - We now have many different ways of delivering educational offerings, hopefully
      tailored to the educational environments and student characteristics. Programs
      vary based on country of origin and delivery location, organisational structures,
      development and delivery technologies, and the business arrangements made between
      providers and agents/students. At Central Queensland University (CQU) we deliver
      the same courses domestically and internationally, often with more than 1000
      students per offering, several times per year across 14 campuses located
      thousands of kilometers apart using face-to-face and/or virtual mode. The
      students are a mix of Australian distance and on campus plus international on
      campus. This chapter builds on the CQU experience managing these large classes,
      particularly within the Faculty of Informatics and Communication, using an
      evolving mix of technologies. The economic realities of tertiary education
      require providers to focus on servicing international markets, including an
      emphasis on student preferences for language of instruction, preferred location
      (campus or distance delivery) and mode of instruction. Educational delivery
      requires development and delivery teamwork, maintenance of consistency (quality)
      in terms of offerings and assessment, appropriate use of technology and cultural
      awareness.

PMID- 15718683
TI  - Evolutionary epistemology and dynamical virtual learning networks.
AB  - This paper is an attempt to define the main features of a new educational model
      aimed at satisfying the needs of a rapidly changing society. The evolutionary
      epistemology paradigm of culture diffusion in human groups could be the
      conceptual ground for the development of this model. Multidimensionality, multi
      disciplinarity, complexity, connectivity, critical thinking, creative thinking,
      constructivism, flexible learning, contextual learning, are the dimensions that
      should characterize distance learning models aimed at increasing the
      epistemological variability of learning communities. Two multimedia educational
      software, Dynamic Knowledge Networks (DKN) and Dynamic Virtual Learning Networks
      (DVLN) are described. These two complementary tools instantiate these dimensions,
      and were tested in almost 150 online courses. Even if the examples are framed in
      the medical context, the analysis of the shortcomings of the traditional
      educational systems and the proposed solutions can be applied to the vast
      majority of the educational contexts.

PMID- 15718684
TI  - The role of evaluation in web-based education.
AB  - The use of web-based education has increased significantly. As a result there is
      a need to focus on methods, employed to evaluate teaching and learning outcomes,
      when technology is used to enhance learning. This chapter provides an overview of
      what, how, and why to assess, test and measure learning. The use of technology
      facilitates a combination of different perspectives within an evaluation process.
      Not only the knowledge and skills of students but also the learning arrangements
      are the focus of assessment. Evaluation generates information which can be used
      for different purposes e.g. planning, implementing and guiding teaching and
      learning processes timely and for the future as well. Based on experiences of
      teaching health informatics, an evaluation model for web-based courses is
      described. The risks of dishonesty and misbehavior related to web-based education
      are recognized.

PMID- 15718685
TI  - Student support infrastructure.
AB  - The development and diffusion of distance learning programmes has made it
      possible for students to choose their preferred location to study and
      consequently, they are expected to be able to use new technologies in order to
      gain the necessary support in a wide range of areas. When universities implement
      distance learning a number of complex issues have to be considered. This chapter
      presents a framework for identifying the most important issues. Furthermore, it
      examines some of the options and problems, which are necessary to consider.

PMID- 15718686
TI  - Recommendations of the International Medical Informatics Association (IMIA) on
      education in health and medical informatics.
AB  - The International Medical Informatics Association (IMIA) agreed on international
      recommendations in health informatics / medical informatics education. These
      should help to establish courses, course tracks or even complete programs in this
      field, to further develop existing educational activities in the various nations
      and to support international initiatives concerning education in health and
      medical informatics (HMI), particularly international activities in educating HMI
      specialists and the sharing of courseware. The IMIA recommendations centre on
      educational needs for health care professionals to acquire knowledge and skills
      in information processing and information and communication technology. The
      educational needs are described as a three-dimensional framework. The dimensions
      are: 1) professionals in health care (physicians, nurses, HMI professionals,
      ...), 2) type of specialisation in health and medical informatics (IT users, HMI
      specialists) and 3) stage of career progression (bachelor, master, ...). Learning
      outcomes are defined in terms of knowledge and practical skills for health care
      professionals in their role (a) as IT user and (b) as HMI specialist.
      Recommendations are given for courses/course tracks in HMI as part of educational
      programs in medicine, nursing, health care management, dentistry, pharmacy,
      public health, health record administration, and informatics/computer science as
      well as for dedicated programs in HMI (with bachelor, master or doctor degree).
      To support education in HMI, IMIA offers to award a certificate for high quality
      HMI education and supports information exchange on programs and courses in HMI
      through a WWW server of its Working Group on Health and Medical Informatics
      Education (http://www.imia.org/wg1).

PMID- 15718688
TI  - Dynamic generation of surgery specific simulators -- a feasibility study.
AB  - Most of the current surgical simulators rely on preset anatomical virtual
      environments (VE). The functionality of a simulator is typically fixed to anatomy
      based specific tasks. This rigid design principle makes it difficult to reuse an
      existing simulator for different surgeries. It also makes it difficult to
      simulate procedures for specific patients, since their anatomical features or
      anomalies cannot be easily replaced in the VE. In this paper, we demonstrate the
      reusability of a modular skill-based simulator, LapSkills, which allows dynamic
      generation of surgery-specific simulations. Task and instrument modules are
      easily reused from LapSkills and the three-dimensional VE can be replaced with
      other anatomical models. We build a nephrectomy simulation by reusing the
      simulated vessels and the clipping and cutting task modules from LapSkills. The
      VE of the kidney is generated with our anatomical model generation tools and then
      inserted into the simulation (while preserving the established tasks and
      evaluation metrics). An important benefit for the created surgery and patient
      specific simulations is that reused components remain validated. We plan to use
      this faster development process to generate a simulation library containing a
      wide variety of laparoscopic surgical simulations. Incorporating the simulations
      into surgical training programs will help collect data for validating them.

PMID- 15718689
TI  - Haptic laparoscopic skills trainer with practical user evaluation metrics.
AB  - Limited sense of touch and vision are some of the difficulties encountered in
      performing laparoscopic procedures. Haptic simulators can help minimize these
      difficulties; however, the simulators must be validated prior to actual use.
      Their effectiveness as a training tool needs to be measured in terms of
      improvement in surgical skills. LapSkills, a haptic skill-based laparoscopic
      simulator, that aims to provide a quantitative measure of the surgeon's skill
      level and to help improve their efficiency and precision, has been developed.
      Explicitly defined performance metrics for several surgical skills are presented
      in this paper. These metrics allow performance data to be collected to quantify
      improvement within the same skill over time. After statistically significant
      performance data is collected for expert and novice surgeons, these metrics can
      be used not only to validate LapSkills, but to also generate a performance scale
      to measure laparoscopic skills.

PMID- 15718690
TI  - Desktop and conference room VR for physicians.
AB  - Virtual environments such as the CAVE and the ImmersaDesk, which are based on
      graphics supercomputers or workstations, are large and expensive. Most physicians
      have no access to such systems. The recent development of small Linux personal
      computers and high-performance graphics cards has afforded opportunities to
      implement applications formerly run on graphics supercomputers. Using PC hardware
      and other affordable devices, a VR system has been developed which can sit on a
      physician's desktop or be installed in a conference room. Affordable PC-based VR
      systems are comparable in performance with expensive VR systems formerly based on
      graphics supercomputers. Such VR systems can now be accessible to most
      physicians. The lower cost and smaller size of this system greatly expands the
      range of uses of VR technology in medicine.

PMID- 15718691
TI  - A biologically derived approach to tissue modeling.
AB  - Our approach to tissue modeling incorporates biologically derived primitives into
      a computational engine (CellSim) coupled with a genetic search algorithm. By
      expanding an evolved synthetic genome CellSim is capable of developing a virtual
      tissue with higher order properties. Using primitives based on cell signaling,
      gene networks, cell division, growth, and death, we have encoded a 64-cell cube
      shaped tissue with emergent capacity to repair itself when up to 60% of its cells
      are destroyed. Other tissue shapes such as sheets of cells also repair
      themselves. Capacity for self-repair is an emergent property derived from, but
      not specified by, the rule sets used to generate these virtual tissues.

PMID- 15718692
TI  - Grid enabled remote visualization of medical datasets.
AB  - We present an architecture for remote visualization of datasets over the Grid.
      This permits an implementation-agnostic approach, where different systems can be
      discovered, reserved and orchestrated without being concerned about specific
      hardware configurations. We illustrate the utility of our approach to deliver
      high-quality interactive visualizations of medical datasets (circa 1 million
      triangles) to physically remote users, whose local physical resources would be
      otherwise overwhelmed. Our architecture extends to a full collaborative, resource
      aware environment, whilst our presentation details our first proof-of-concept
      implementation.

PMID- 15718693
TI  - Surface scanning soft tissues.
AB  - We investigate and report a method of 3D virtual organ creation based on the RGB
      color laser surface scanning of preserved biological specimens. The surface
      attributes of these specimens result in signal degredation and increased scanning
      time. Despite these problems we are able to reproduce 3D virtual organs with both
      accurate topology and colour consistency capable of reproducing pathological
      lesions.

PMID- 15718694
TI  - Validation of a bovine rectal palpation simulator for training veterinary
      students.
AB  - Bovine rectal palpation is a necessary skill for a veterinary student to learn.
      However, lack of resources and welfare issues currently restrict the amount of
      training available to students in this procedure. Here we present a virtual
      reality based teaching tool -- the Bovine Rectal Palpation Simulator -- that has
      been developed as a supplement to existing training methods. When using the
      simulator, the student palpates virtual objects representing the bovine
      reproductive tract, receiving feedback from a PHANToM haptic device (inside a
      fibreglass model of a cow), while the teacher follows the student's actions on
      the monitor and gives instruction. We present a validation experiment that
      compares the performance of a group of traditionally trained students with a
      group whose training was supplemented with a simulator training session. The
      subsequent performance in the real task, when examining cows for the first time,
      was assessed with the results showing a significantly better performance for the
      simulator group.

PMID- 15718695
TI  - Predictive biosimulation and virtual patients in pharmaceutical R and D.
AB  - In the automotive, telecommunication, and aerospace industries, modeling and
      simulation are used to understand the behavior and outcomes of a new design well
      before production begins, thereby avoiding costly failures. In the pharmaceutical
      industry, failures are not typically identified until a compound reaches the
      clinic. This fact has created a productivity crisis due to the high failure rate
      of compounds late in the development process. Modeling and simulation are now
      being adopted by the pharmaceutical industry to understand the complexity of
      human physiology and predict human response to therapies. Additionally, virtual
      patients are being used to understand the impact of patient variability on these
      predictions. Several case studies are provided to illustrate the technology's
      application to pharmaceutical R and D and healthcare.

PMID- 15718696
TI  - Simulating surgical incisions without polygon subdivision.
AB  - Modeling cuts, bleeding and the insertion of surgical instruments are essential
      in surgical simulation. Both visual and haptic cues are important. Current
      methods to simulate cuts change the topology of the model, invalidating pre
      processing schemes or increasing the model's complexity. Bleeding is frequently
      modeled by particle systems or computational fluid dynamics. Both can be
      computationally expensive. Surgical instrument insertion, such as intubation, can
      require complex haptic models. In this paper, we describe methods for simulating
      surgical incisions that do not require such computational complexity, yet
      preserve the visual and tactile appearance necessary for realistic simulation.

PMID- 15718697
TI  - 3D Real-time FEM based guide wire simulator with force feedback.
AB  - Minimally invasive surgical techniques using catheter is now used in many
      procedures. Development of surgical training of such procedures requires real
      time simulation of tool-organ interaction. In such processes, each subsequent
      step of interaction would be based on the current configuration of the surgical
      tool (guidewire in this case), leading to development of techniques to solve and
      visualize the configuration of tool at every time step. This paper presents a
      Finite Element (FEM) based approach to simulate the tool-organ interaction.

PMID- 15718698
TI  - Determining the efficacy of an immersive trainer for arthroscopy skills.
AB  - The present study examined the effectiveness of an immersive arthroscopic
      simulator for training naive participants to identify major anatomical structures
      and manipulate the arthroscope and probe. Ten psychology graduate students
      engaged in five consecutive days of practice sessions with the arthroscopic
      trainer. Following each session, participants were tested to see how quickly and
      accurately they could identify 10 anatomical landmarks and manipulate the
      arthroscope and probe. The results demonstrated steady learning on both tasks.
      For the anatomy task, participants correctly identified an average of 7.7 out of
      10 structures correctly in the first session and 9.5 in the last. During the
      manipulation task, participants collided 53.5 times with simulated tissues in the
      first session and 13.2 times during the final session. Participants (n=9) also
      demonstrated minimal performance degradation when tested 4 weeks later. These
      data suggest that the immersive arthroscopic trainer might be useful as an
      initial screening or training tool for beginning medical students.

PMID- 15718699
TI  - Teaching intravenous cannulation to medical students: comparative analysis of two
      simulators and two traditional educational approaches.
AB  - This study examines the effectiveness of two virtual reality simulators when
      compared with traditional methods of teaching intravenous (IV) cannulation to
      third year medical students. Thirty-four third year medical students were divided
      into four groups and then trained to perform an IV cannulation using either
      CathSim, Virtual I.V., a plastic simulated arm or by practicing IV placement on
      each other. All subjects watched a five minute training video and completed a
      cannulation pretest and posttest on the simulated arm. The results showed
      significant improvement from pretest to posttest in each of the four groups.
      Students trained on the Virtual I.V. showed significantly greater improvement
      over baseline when compared with the simulated arm group (p<.026). Both
      simulators provided at least equal training to traditional methods of teaching, a
      finding with implications for future training of this procedure to novices.

PMID- 15718700
TI  - Validation of SimPL -- a simulator for diagnostic peritoneal lavage training.
AB  - This study describes a comparison between an animal model and a haptic enabled,
      needle based, graphical user interface simulator (SimPL), for teaching Diagnostic
      Peritoneal Lavage (DPL). Forty novice medical students were divided into two
      groups and then trained to perform a DPL on either a pig or the SimPL. All
      subjects completed a pre and post test of basic knowledge and were tested by
      performing a DPL on a TraumaMan mannequin and evaluated by two trauma surgeons
      blinded to group. The results showed significant improvement over baseline
      knowledge in both groups but more so in the SimPL group. The simulator group
      performed better on site selection (p<0.001) and technique (p<0.002) than those
      who trained on a pig. The finding that a simulator is superior to an animal model
      for teaching an important skill to medical students has profound implications on
      future training and deserves further study.

PMID- 15718701
TI  - Challenges in presenting high dimensional data to aid in triage in the DARPA
      virtual soldier project.
AB  - One of the goals of the DARPA Virtual Soldier Project is to aid the field medic
      in the triage of a casualty. In Phase I, we are currently collecting 12 baseline
      experimental physiological variables and a cardiac gated Computed Tomography (CT)
      imagery for use in an prototyping a futuristic electronic medical record, the
      "Holomer". We are using physiological models and Kalman filtering to aid in
      diagnosis and predict outcomes in relation to cardiac injury. The physiological
      modeling introduces another few hundred variables. Reducing the complexity of the
      above into easy-to-read text to aid in the triage by the field medic is the
      challenge with multiple display solutions. A description of the possible
      techniques follows.

PMID- 15718702
TI  - A web-based remote collaborative system for visualization and assessment of semi
      automatic diagnosis of liver cancer from CT images.
AB  - We propose a web-based collaborative CAD system allowing for the remote
      communication and data exchange between radiologists and researchers in computer
      vision-based software engineering. The proposed web-based interface is
      implemented in the Java Advanced Imaging Application Programming Interface. The
      different modules of the interface allow for 3D and 2D data visualization, as
      well as for the parametric adjustment of 3D reconstruction process. The proposed
      web-based CAD system was tested in a pilot study involving a limited number of
      liver cancer cases. The successful system validation in the feasibility stage
      will lead to an extended clinical study on CT and MR image databases.

PMID- 15718703
TI  - Heterogeneous displays for surgery and surgical simulation.
AB  - Instruments and procedures continue to become more complex and challenging, but
      the display environments to which these technologies are connected have not kept
      pace. Display real-estate (the size and resolution of the display), the
      configurability of the display, and the ability for display systems to
      incorporate, fuse and present diverse informational sources are limiting factors.
      The capabilities of display technologies are far exceeded by the procedures and
      instruments that rely on them. In this paper we show how to break free from
      display constraints by moving forward with a hybrid, heterogeneous display
      framework that preserves key characteristics of current systems (low latency,
      specialized devices). We have engineered a hybrid display and are currently using
      it to build a surgical simulation and training environment within which we can
      evaluate both the technology and the performance of subjects using the
      technology.

PMID- 15718704
TI  - Visualization of treatment evolution using hardware-accelerated morphs.
AB  - The observation of the evolution of a course of treatment can provide a powerful
      tool in understanding its efficacy. To visualize this, we produce animations
      allowing the visualization, as a function of time, of lesions in an organ. Such
      animations can be used in teaching or for patient education, influencing a
      patient's decision of following a course of treatment. The animation produced is
      a metamorphosis, or morph, describing how a source shape (pre-treatment)
      gradually deforms into a target shape (post-treatment). We implemented our method
      using the programming capabilities of current graphics cards (also known as
      graphics processing units or GPUs), so both visualization of the volumes and
      morph generation are performed in real-time. We demonstrate our method on data
      from a patient's liver with lymphoma that was treated with chemotherapy and is
      currently on remission.

PMID- 15718705
TI  - Real-time rendering of radially distorted virtual scenes for endoscopic image
      augmentation.
AB  - This paper presents a method for rendering radially distorted virtual scenes in
      real-time using the programmable fragment shader commonly found in many main
      stream graphics hardware. We show that by using the pixel buffer and the fragment
      shader, it is possible to augment the endoscopic display with distorted virtual
      images.

PMID- 15718706
TI  - Tracking the domain: the medical modeling and simulation database.
AB  - To foster awareness of the magnitude and breadth of activity and to foster
      collaboration among the participants, the National Center for Collaboration in
      Medical Modeling and Simulation (NCCMMS) has created the Medical Modeling and
      Simulation Database (MMSD). The MMSD consists of two web-based, searchable
      compilations: one, the Research Database, that contains bibliographic information
      on published articles and abstracts (where available) and a second, the Companies
      and Projects Database, that maintains contact information for research centers,
      development and application programs, journals and conferences. NCCMMS is
      developing the MMSD to increase awareness of the breadth of the medical modeling
      domain and to provide a means of fostering collaboration and bringing like-minded
      organizations and researchers into more frequent contact with each other, thus
      speeding advancement of medical modeling and simulation.

PMID- 15718707
TI  - The ViCCU Project -- achieving virtual presence using Ultrabroadband internet in
      a Critical Clinical application -- initial results.
AB  - The ViCCU (Virtual Critical Care Unit) Project sought to address the problems of
      shortages of Critical Care staff by developing a system that could use the
      capabilities of Ultrabroadband networks so as to have a Critical Care Specialist
      virtually present at a distant location. This is not possible in a clinically
      useful way with current systems. A new system (ViCCU) was developed and deployed.
      Critically ill or injured patients are now routinely assessed and managed
      remotely using this system. It has led to a more appropriate level of transfers
      of patients and the delivery of a quality of clinical service not previously
      available. This paper describes the history of the project, its novelty, the
      clinically significant technical aspects of the system and its deployment. The
      initial results to the end of September 2004 are described.

PMID- 15718708
TI  - High stakes assessment using simulation -- an Australian experience.
AB  - The use of simulation for high stakes assessment has been embedded in the New
      South Wales Medical Practice Act and has been used for high stakes assessment on
      a number of occasions. Simulation has rarely been used in this manner elsewhere
      in the world. We outline the use of simulation in particular focussing on its
      relationship to a performance assessment programme featuring performance focus,
      peer assessment of standards, an educative, remedial and protective framework,
      strong legislative support and system awareness.

PMID- 15718709
TI  - The virtual pediatric standardized patient application: formative evaluation
      findings.
AB  - This paper presents formative (i.e., not final project) evaluation data from the
      use of a responsive virtual human training application by medical students
      rotating through Pediatrics and by Pediatric medical educators. We are encouraged
      by the evaluation results and believe the iterative development strategies
      employed and the subsequent refinements in the scenarios will lead to important
      instructional and assessment tools for medical educators.

PMID- 15718710
TI  - The visible human and digital anatomy learning initiative.
AB  - A collaborative initiative is starting within the Internet2 Health Science
      community to explore the development of a framework for providing access to
      digital anatomical teaching resources over Internet2. This is a cross-cutting
      initiative with broad applicability and will require the involvement of a diverse
      collection of communities. It will seize an opportunity created by a convergence
      of needs and technical capabilities to identify the technologies and standards
      needed to support a sophisticated collection of tools for teaching anatomy.

PMID- 15718711
TI  - Laparoscopic task recognition using Hidden Markov Models.
AB  - Surgical skills assessment has been paid increased attention over the last few
      years. Stochastic models such as Hidden Markov Models have recently been adapted
      to surgery to discriminate levels of expertise. Based on our previous work
      combining synchronized video and motion analysis we present preliminary results
      of a HMM laparoscopic task recognizer which aims to model hand manipulations and
      to identify and recognize simple surgical tasks.

PMID- 15718712
TI  - Intraoperative augmented reality: the surgeons view.
AB  - Augmented Reality (AR) is a promising tool for intraoperative visualization. Two
      different AR systems, one projector based, one based on see-through glasses were
      used on patients. The task was the transfer of preoperative planning into the
      intraoperative reality, or the visualization of space occupying lesions,
      respectively. The intraoperative application of both systems is discussed from
      the surgeons point of view.

PMID- 15718713
TI  - A vision-based surgical tool tracking approach for untethered surgery simulation
      and training.
AB  - This paper presents progress in the development of an untethered surgery
      simulation and training system. A surgical trainee interacts with the simulation
      in the most natural way possible-using standard, untethered surgical tools and
      hands. This natural interface requires innovations in tracking, haptic feedback,
      and visualization. This article describes the approach used for tool tracking
      with color cameras. A novel tracking algorithm is used to identify the type of
      tool, its position, and its orientation. Integration of the vision system with
      the tissue deformation and visualization modules is also discussed.

PMID- 15718714
TI  - Haptic simulation of the milling process in temporal bone operations.
AB  - A VR-simulation system for educating surgeons of the temporal bone milling
      processes is presented in this paper. E.g. the milling process that occurs during
      the removal of certain cancer tumors in the brain. The research project is
      recently started up and this paper is an introduction to the bone milling
      simulation topic. We present how the graphical rendering of the temporal bone is
      done. Acquired data are managed using the Marching cubes algorithm to perform a
      visual representation. A re-production of iso-surfaces will represent the
      material removal occurred during the milling process. Force models are discussed
      and will be implemented in the H3D API, which is used to control the virtual
      simulation and collision detection. Equipment, implementation and future work are
      also presented in the paper.

PMID- 15718715
TI  - Soft tissue deformation using a nonlinear hierarchical finite element model with
      real-time online refinement.
AB  - Simulating soft tissue deformation in real-time is a requirement for
      realistically rendering the VR interaction between human organs and surgical
      tools. Finite Element Model (FEM) describes complex mechanical and physiological
      behaviour but it is computationally too demanding especially when a nonlinear
      model is to be implemented. For this reason, we introduce a multiresolution
      approach to FEM that only employs the region of the object under deformation to
      find the solution of the differential equations of motion. In order to increase
      the quality of the deformation, refinement of the original mesh is performed with
      the insertion of new surface nodes in real-time in the region of interaction. To
      guarantee the stability of the nonlinear model, the presence of flat tetrahedra
      (slivers) has to be avoided; therefore a sliver elimination technique has been
      implemented resulting in a more stable simulation.

PMID- 15718716
TI  - Modeling biologic soft tissues for haptic feedback with an hybrid multiresolution
      method.
AB  - The simulation of realistic surgical procedures requires specialized optimized
      algorithms for the models of organs and tissues, which should comply both with
      accuracy of results and run-time computation. This paper provides a numerical
      method for implementing deformation of soft tissues for haptic feedback that
      makes use of a hybrid pre-computation scheme.

PMID- 15718717
TI  - Control of laparoscopic instrument motion in an inanimate bench model:
      implications for the training and evaluation of technical skills.
AB  - Laparoscopic surgery requires new methods of technical competency evaluation, as
      well as training. The first purpose was to assess the differences in motion
      characteristics between the tip of the instrument and the wrist. The second
      purpose was to determine whether similar control strategies are used to move
      instruments in virtual reality and bench model environments. Surgically naive
      participants were required to tap a laparoscopic instrument between two targets
      that differed in size and separation distance. Large amplitude movements were
      controlled with the movements of the wrist and small amplitude with the wrist and
      the fingers (p<.001). Participants utilized the flexibility of the skin of the
      laparoscopic trainer to facilitate their movements. These results suggest that
      monitoring the motions of the instrument tip is a more precise indication of its
      motions than are motions of the wrist when movements of small amplitudes are
      produced. Moreover, in order to increase fidelity, VR trainers should simulate
      the flexibility of the real structures around the insertion of the instrument.

PMID- 15718718
TI  - Tearing of membranes for interactive real-time surgical training.
AB  - Tearing for interactive real-time surgical training is a problem rarely discussed
      in scientific publications. In this paper, an approach is presented to model the
      tearing of membranes. Based on a mesh of mass nodes connected by springs and
      triangles tears propagate along the springs of the mesh. Springs and triangles at
      the crack are divided up between both sides, keeping the number of triangles
      constant. Node stress indicates when and where the membrane tears. Tear threshold
      of a node depends on the node's location in the mesh. Edge nodes tear more easily
      than internal nodes. Nodes at the end of a crack have the lowest threshold to
      favor the propagation of already created cracks. Compared to a straightforward
      solution of the problem, the deletion of over stretched springs, the approach has
      some advantages. The presented algorithm shows a more plausible result for small
      resolutions that are used by the real-time simulation of stiff materials. On high
      resolution meshes, there is only little difference between both approaches. Two
      training modules for the ophthalmo-surgical simulator EYESI use the presented
      tearing method to model realistic membrane tearing.

PMID- 15718719
TI  - Interactive real-time simulation of an endoscopic polyp removal.
AB  - The paper describes methods used for an interactive real-time training simulation
      of an endoscopic procedure: the removal of a colon polyp. Biomechanical
      simulation of the polyp is provided by a Finite Element approach. A combination
      of animation and simulation models the flexing, retraction and deployment of the
      used instrument, a wire sling. The presented method enables a training simulation
      of the surgery, based on the endoscopic simulator EndoSim.

PMID- 15718720
TI  - Surgical robot setup simulation with consistent kinematics and haptics for
      abdominal surgery.
AB  - Preoperative simulation and planning of surgical robot setup should accompany
      advanced robotic surgery if their advantages are to be further pursued. Feedback
      from the planning system will plays an essential role in computer-aided robotic
      surgery in addition to preoperative detailed geometric information from patient
      CT/MRI images. Surgical robot setup simulation systems for appropriate trocar
      site placement have been developed especially for abdominal surgery. The motion
      of the surgical robot can be simulated and rehearsed with kinematic constraints
      at the trocar site, and the inverse-kinematics of the robot. Results from
      simulation using clinical patient data verify the effectiveness of the proposed
      system.

PMID- 15718721
TI  - Development of a navigation function for an endosocopic robot surgery system.
AB  - An endoscopic robot system that we reported at MMVR11 is able to perform various
      surgical procedures in the stomach by using two manipulators. However, it is
      difficult for surgeons to recognize the 3D location and the direction of the
      endoscope's tip in the abdominal region during robotic surgery. In this research,
      we have developed a navigation function that enables image-guided surgery by
      superimposing the patient's abdominal organ structure onto the endoscopic image.
      In this paper, we describe the overview of the navigation for the robot system
      and the result of an animal experiment done while applying the system.

PMID- 15718722
TI  - Development of a 3D visualization system for surgical field deformation with
      geometric pattern projection.
AB  - Intra-operative navigation in which the target position is provided to assist an
      intuitive understanding of the surgical field has been studied and applied in
      many clinical areas. Position measurement of a surgical field is usually
      performed with a magnetic sensor, a marker type optical position sensor. For
      navigation of hard tissue, the measurement of several markers dispersedly located
      on the surface is enough to detect the position of an object that can be assumed
      as a rigid body. However, for the navigation of soft tissue such as skin and
      liver, a sensor that can measure the deformation of the object surface time
      sequentially would be essential. We have developed a 3D visualization system for
      surgical field deformation with geometric pattern projection. In an animal
      experiment, the registration of preoperative 3D organ model could be done with
      the time-sequentially updated surface deformation data. In the video image of
      surgical field, the inner structure model of organ could be superimposed
      successfully.

PMID- 15718723
TI  - In vivo force during arterial interventional radiology needle puncture
      procedures.
AB  - To adequately simulate the forces generated during interventional radiological
      (IR) procedures, non intrusive in-vivo methods must be used. Using finger tip
      mounted, non intrusive capacitance force sensor pads (PPS, Los Angeles,
      California) we have been able to measure the forces involved in interventional
      radiology without a change in procedure technique. Data acquired during the
      process of calibration of the capacitance pads in conjunction with extensive in
      vitro needle puncture force measurement using a commercially available tensile
      tester (Nene Industries, UK) are presented here.

PMID- 15718724
TI  - The virtual terrorism response academy: training for high-risk, low-frequency
      threats.
AB  - The Virtual Terrorism Response Academy is a reusable virtual learning environment
      to prepare emergency responders to deal with high-risk, low-frequency events in
      general, terrorist attacks in particular. The principal learning strategy is a
      traditional one: apprenticeship. Trainees enter the Academy and travel through
      its halls, selecting different learning experiences under the guidance of
      instructors who are simultaneously master practitioners and master trainers. The
      mentors are real individuals who have been videotaped according to courseware
      designs; they are subsequently available at any time or location via broadband
      Internet or CD-ROM. The Academy features a Simulation Area where trainees are
      briefed on a given scenario, select appropriate resources (e.g., protective
      equipment and hazmat instruments), then enter a 3-dimensional space where they
      must deal with various situations. Simulations are done under the guidance of a
      master trainer who functions as a coach, asking questions, pointing out things,
      explaining his reasoning at various points in the simulation. This is followed by
      a debriefing and discussion of lessons that could be learned from the simulation
      and the trainee's decisions.

PMID- 15718725
TI  - Real-time ultrasonography simulator based on 3D CT-scan images.
AB  - A new method for real-time simulation of ultrasonography is presented. This
      method uses directly 3D enhanced helical CT-scan images. The originality of this
      method is that it can be run directly on real patient data with no need of any
      pretreatment.

PMID- 15718726
TI  - Fuzzy classification: towards evaluating performance on a surgical simulator.
AB  - Computer-based surgical simulators such as the MIST-VR are able to provide
      scoring metrics such as time taken to complete a task, number of errors made, and
      economy of movement. Using MIST-VR's basic metrics, we explored the possibility
      of classifying skill levels using fuzzy logic. Our objective was to create a
      fuzzy classifier capable of classifying the performance of a subject training on
      a surgical simulator into 1 of 3 categories: Novice, Intermediate, and Expert. To
      accomplish this, we needed to establish a baseline skill level for each category.
      We had four laparoscopic surgeons, four surgical assistants/residents and four
      non-surgical staff/students with no laparoscopic experience perform two basic
      tasks on the simulator involving the placement of a ball into a box. We have
      found, through this preliminary study, that the results were inconclusive. We
      suspected a number of issues such as the size of our sample space used to train
      our classifier, and the difficulty of the chosen tasks adversely affected our
      results.

PMID- 15718727
TI  - Structural flexibility of laparoscopic instruments: implication for the design of
      virtual reality simulators.
AB  - In accordance with the Practice Specificity Theory, training on models that
      closely resemble real life scenarios is most beneficial to learning. Research in
      the virtual reality (VR) simulation, as a potential teaching and evaluation tool,
      concentrated on the design of trainers to resemble operating room (OR)
      conditions. The purpose of the present investigation was to determine the
      structural flexibility of laparoscopic instruments of different materials and
      diameters under a wide range of stresses. Incorporating the mechanical properties
      of these instruments into the algorithms can prove to further increase the
      fidelity of VR simulators. The amount of deviation from pre-stress position in
      the instruments' shaft was measured with infrared markers and used as the index
      of structural flexibility. All instruments deviated considerably with the largest
      deviations observed for the small disposable, and lowest for the large reusable
      instruments. There was a linear relation between the stress and deviation for all
      instruments, which varied as a function of diameter. Similar instrument
      deviations were observed during cholecystectomy performed on porcine liver. Our
      findings show that laparoscopic instruments are not rigid bodies and are prone to
      significant deviations during standard laparoscopic procedures. This suggests
      that the structural flexibility of laparoscopic instruments should be modeled in
      the design of VR simulators.

PMID- 15718728
TI  - A networked haptic virtual environment for teaching temporal bone surgery.
AB  - This paper describes a computer system for teaching temporal bone surgery using
      networked haptic work benches. The system enables an instructor and student to
      collaboratively explore and drill a volumetric bone model including significant
      anatomical features. Subjective evaluations by otologists have been favourable,
      and experimental trials are planned.

PMID- 15718729
TI  - Real-time haptic interface for VR colonoscopy simulation.
AB  - Colonoscopy is an endoscopic medical procedure where the colon of the patient is
      examined. This minimally invasive technique is performed with a colonoscope, a
      long tube with an integrated imaging device at its tip. The doctors performing
      these procedures require high skills in multiple domains such as hand-eye
      coordination, visualization, safety and ease at guiding flexible endoscopes. The
      importance of training colonoscopy procedures rises with the growth of variety of
      colon diseases. In order to safely train surgeons to these procedures, a computer
      assisted haptic simulator is proposed. This paper describes both the haptic
      hardware interface and virtual reality software that compose the training system.
      A high friction belt is used to render the required forces and to insure the
      absence of slippage. A differential drive actuated with two DC motors enables to
      set the system into translation and rotation. A virtual reality environment has
      been developed to provide real-time visualisation and force feedback.

PMID- 15718730
TI  - Computational simulation of penetrating trauma in biological soft tissues using
      the material point method.
AB  - The objective of this research was to develop realistic computational models for
      soft tissues subjected to finite deformation and failure, and to test these
      models in the context of numerical simulations of penetrating trauma injuries. A
      transversely isotropic hyperelastic model with strain-based failure criteria was
      used to represent the behavior of anisotropic soft tissue. The constitutive model
      was implemented into an existing numerical code based on the Material Point
      Method (MPM). The penetration of a low-speed bullet through a myocardium material
      slab was simulated and several wounding scenarios were analyzed and compared. The
      material symmetry, the type of contact modeled between the bullet and the soft
      tissue and the bullet speed were shown to have a significant influence on the
      wound profile.

PMID- 15718731
TI  - Adaptive soft tissue deformation for a virtual reality surgical trainer.
AB  - Real time tissue deformation is an important aspect of interactive virtual
      reality (VR) environments such as medical trainers. Most approaches in deformable
      modelling use a fixed space discretization. A surgical trainer requires high
      plausibility of the deformations especially in the area close to the instrument.
      As the area of intervention is not known a priori, adaptive techniques have to be
      applied. We present an approach for real time deformation of soft tissue based on
      a regular FEM mesh of cube elements as opposed to a mesh of tetrahedral elements
      used by the majority of soft tissue simulators. A regular mesh structure
      simplifies the local refinement operation as the elements topology and stiffness
      are known implicitly. We propose an octree-based adaptive multiresolution
      extension of our basic approach. The volumetric representation of the deformed
      object is created automatically from medical images or by voxelization of a
      surface model. The resolution of the volumetric representation is independent of
      the surface geometry resolution. The surface is deformed according to the
      simulation performed on the underlying volumetric mesh.

PMID- 15718732
TI  - Simulation of color deficiency in virtual reality.
AB  - Color deficiency protanopia is simulated in a virtual home environment. A color
      database is created to set the corresponding relation between each color for
      normal vision and for protanopia. Based on this database, a second texture system
      is set up for the home model. The proper texture system is used according to the
      user's choice on the interactive menu.

PMID- 15718733
TI  - Improving the visual realism of virtual surgery.
AB  - In this work we focus our attention on improving the visual realism of virtual
      surgery. A synthetic solution by innovative use of various image-based rendering
      methods is presented for realistic rendering of virtual surgery scenes. We have,
      for the first time, developed a methodology for generating virtual surgery scenes
      with realistic glistening effects by a combination of various image-based
      rendering techniques, including image mosaicing and view-dependent texture
      mapping. Realistic examples are presented to showcase the results.

PMID- 15718734
TI  - ChiroSensor -- an array of non-invasive sEMG electrodes.
AB  - It is shown that the statistical analysis of the sEMG signals recorded by the
      ChiroSensors along the paraspinal muscles during Network Spinal Analysis (NSA)
      provides objective confirmation of the physiological reality as perceived by the
      practitioner as it relates to levels of care and spinal injury recovery.

PMID- 15718735
TI  - Multiple contact approach to collision modelling in surgical simulation.
AB  - In this paper we present a technique for the modelling of realistic collisions
      between arbitrary rigid surgical tools and deformable geometry that is
      independent of the resolution of colliding objects. We use a spatial hash table
      to provide an efficient narrow-phase collision detection and modelling backend.
      This is combined with previous work on collision modelling in our surgical
      simulation environment to model realistic collisions and collision response at
      haptic rates.

PMID- 15718736
TI  - Visualization of surgical 3D information with projector-based augmented reality.
AB  - For visualizing surgical information (operation plans) directly onto the patient
      a projector-based augmented reality system is used for cranio-maxillofacial
      surgery. A prototype is introduced which has been evaluated in the first clinical
      cases. In a new setup with a second video projector it is now possible to give
      additionally 3D information for localization and orientation (6DoF). With this
      method the repositioning of a bone segment is intuitive and exact applicable.

PMID- 15718737
TI  - Facial plastic surgery planning using a 3D surface deformation tool.
AB  - The range of facial malformations that plastic surgeons are asked to alter is
      wide. Even a subtle deformity may strongly affect both the way a person perceives
      herself as well as her quality of life. Moreover, the changes achieved during
      craniofacial surgery often result in dramatic differences on the face of the
      patient. Consequently, both surgeons and patients would benefit from the visual
      approximation of the outcome of the operation provided by adequate three
      dimensional planning tools. In this paper we propose a three-dimensional texture
      mapped surface deformation tool as part of a planning system for rhinoplasty.

PMID- 15718738
TI  - The haptic kymograph: a diagnostic tele-haptic device for sensation of vital
      signs.
AB  - The kymograph is device for measuring and presenting pressure-based signals, such
      as human heart beat and artery volume pressure. The Haptic Kymograph is a
      haptically-enhanced tele-medicine system which is used to acquire human vital
      signs and then to transform these signs into sensible, scalable and ubiquitous
      media so that a user can easily comprehend subtle and ambiguous signals in a
      remote place. In an experiment setup a patient's artery pressure pulse was
      captured at 200 Hz of sampling rate, transmitted via TCP/IP network, and
      replicated in a remote place using a PHANToM haptic device coupled with a real
      time visual interface. In this paper we report our recent progresses in
      developing a low-cost input system, network interfaces and haptic replication of
      the human artery volume pulse signal.

PMID- 15718739
TI  - A study of the method of the video image presentation for the manipulation of
      forceps.
AB  - Recently, surgical operations have sometimes been tried under laparoscopic video
      images using teleoperation robots or forceps manipulators. Therefore, in this
      paper, forceps manipulation efficiencies were evaluated when images for
      manipulation had some transmission delay (Experiment 1), and when the convergence
      point of the stereoscopic video cameras was either fixed and variable (Experiment
      2). The operators' tasks in these experiments were sewing tasks which simulated
      telesurgery under 3-dimensional scenography. As a result of experiment 1, the
      operation at a 200+/-100 ms delay was kept at almost the same accuracy as that
      without delay. As a result of experiment 2, work accuracy was improved by using
      the zooming lens function; however the working time became longer. These results
      seemed to show the relation of a trade-off between working time and working
      accuracy.

PMID- 15718740
TI  - Collaborative biomedical data exploration in distributed virtual environments.
AB  - Imaging techniques such as MRI, fMRI, CT and PET have provided doctors with a
      means to acquire high-resolution biomedical images that serve as the foundation
      for the diagnosis and treatment of diseases. Experts with a multitude of
      backgrounds, including radiologists, anatomists, psychiatrists and
      neuroscientists now collaboratively analyze the same images to extract a better
      understanding of the encoded information. Unfortunately, access to these
      specialists at the same physical location is not always possible and new tools
      and techniques are required to facilitate simultaneous and collaborative
      exploration of volumetric data between spatially separated domain experts. This
      paper presents CVMED, a collaborative visualization environment for volumetric
      biomedical data-sets, supporting heterogeneous hardware, rendering and display
      systems connected via heterogeneous networks. CVMED provides the user with the
      algorithms and tools for stereoscopic as well as monoscopic data visualization
      and annotation along with the middleware needed to exchange the resulting visuals
      between all participants in real-time.

PMID- 15718741
TI  - FEM-based soft tissue destruction model for ablation simulator.
AB  - In surgical procedures, ablation is one of the most difficult skills to train and
      acquire. For the risk of ablation failure, ablation training environments are
      desired. This paper proposes FEM-based deformation and destruction soft tissue
      model for ablation training simulator. The proposed model employs shearing stress
      hypothesis. The result of simulation experiments shows that the model can express
      different destruction progression by manipulation.

PMID- 15718742
TI  - The VREST learning environment.
AB  - The VREST learning environment is an integrated architecture to improve the
      education of health care professionals. It is a combination of a learning,
      content and assessment management system based on virtual reality. The generic
      architecture is now being build and tested around the Lichtenstein protocol for
      hernia inguinalis repair.

PMID- 15718743
TI  - MVL: medical VR simulation library.
AB  - In the last ten years, medical VR techniques have much progress and many
      simulators have been developed for education, planning, rehearsal and so on. On
      the other hand, developing a simulator takes much more labor and cost. In this
      paper, we propose MVL: Medical Virtual reality simulation Library, which supports
      simulation of several significant medical manipulations considering multiple
      organ interaction. The result of developing simulators using MVL confirmed
      validity about variety and developing cost.

PMID- 15718744
TI  - Haptic device for colonoscopy training simulator.
AB  - A new 2-DOF haptic device for colonoscopy training simulator employing flexible
      endoscopes, is developed. The user operates the device in translational and roll
      directions. The developed folding guides of the device keep the endoscope tube
      straight. This helps transmit large decoupled forces of the colonoscopy
      simulation to the user. The device also includes a mechanism to detect jiggling
      motion of the scopes to allow users to practice this important skill of the
      colonoscopy. The device includes PD controller to compensate the inertia and
      friction effects. This provides the users with better transparent sensation of
      the simulation.

PMID- 15718745
TI  - Developing a simulation-based training program for medical first responders.
AB  - A major stumbling block for widespread incorporation of simulators into EMT
      training includes the limited availability of curricula infrastructure linking
      the key components of skills, scenarios, and measures as well as the expertise
      required to run such programs. To meet these needs we are developing a training
      program for first responders that uses mannequin-based simulator technology
      effectively to fill the identified training need for valid meaningful scenarios
      that can be integrated into the curriculum and are applicable for a variety of
      EMT skill levels. The program will provide detailed scenarios, instructions for
      administering the program, and measures for performance feedback. Each scenario
      will exercise a combination of task work and cognitive skills and the set of
      scenarios will span all of the higher-level skills that have been identified as
      benefiting from targeted training.

PMID- 15718746
TI  - A mechanical contact model for the simulation of obstetric forceps delivery in a
      virtual/augmented environment.
AB  - During the process of human childbirth, obstetric forceps delivery can be a
      justified alternative to emergency Caesarean section when normal vaginal delivery
      proves difficult or impossible. Currently, training of forceps interventions is
      mainly done on real patients which poses a risk. This paper describes a pilot
      project on the simulation of training of obstetric forceps delivery, using
      Virtual Reality technology. We first give a brief historical review of the
      concept of 'birth simulation' and describe the current implementation of the
      interface. Then we report a number of experiments, conducted to test the
      feasibility of a real-time mechanical contact model to describe the interaction
      between the forceps and fetal head, eventually to be interfaced with a multi
      purpose haptic feedback device. It is concluded that an explicit dynamic model to
      calculate the deformation of the main fetal skull bones only, or a quasi-static
      model to calculate the deformation of the fetal head in its entirety, can reach
      real-time performance.

PMID- 15718747
TI  - Instant electronic patient data input during emergency response in major disaster
      setting: report on the use of a rugged wearable (handheld) device and the concept
      of information flow throughout the deployment of the disaster response upon
      hospital admission.
AB  - A hard- and software solution has been conceived, realized, produced and used to
      gather clinical information about disaster victims in the field in such a way
      that it makes the different efforts made by mass casualty incident management
      managers and first responders work more efficient, ergonomic, safe and useful for
      further scientific and statistic analysis.

PMID- 15718748
TI  - Remote console for virtual telerehabilitation.
AB  - The Remote Console (ReCon) telerehabilitation system provides a platform for
      therapists to guide rehabilitation sessions from a remote location. The ReCon
      system integrates real-time graphics, audio/video communication, private
      therapist chat, post-test data graphs, extendable patient and exercise
      performance monitoring, exercise pre-configuration and modification under a
      single application. These tools give therapists the ability to conduct training,
      monitoring/assessment, and therapeutic intervention remotely and in real-time.

PMID- 15718749
TI  - Improved virtual surgical cutting based on physical experiments.
AB  - Simulation of surgical cutting is one of the most challenging tasks in the
      development of a surgery simulator. Changes in topology during simulation make
      any precomputed data meaningless. Moreover, the process is nonlinear and given
      the complexity of soft tissue mechanics, the underlying physics is not well
      understood. Therefore, fully realistic procedures for the simulation of surgical
      cutting at real time rates on single processor machines is possibly out of reach.
      We developed a geometry-based algorithm that is capable of simulating progressive
      cutting without increasing the number of primitives and have coupled it to a
      meshfree physically based simulation scheme. In this paper we enhance a
      geometrically efficient cutting algorithm by including physical information from
      actual cutting experiments.

PMID- 15718750
TI  - A haptic-enabled simulator for cricothyroidotomy.
AB  - Cricothyroidotomy is an emergency procedure that is performed when the patient's
      airway is blocked, and less invasive attempts to clear it have failed.
      Cricothyroidotomy has been identified as an essential skill for military
      readiness. This training is relevant to more than 40,000 U.S. military medics,
      and thousands of civilian health care providers. Current training methods use
      animals, cadavers and plastic mannequins. Animal models do not have the correct
      anatomy. Cadavers do not have the correct physiology. Mannequins do not
      adequately cover the full range of anatomical variations. In this paper, we
      describe our effort to build a computer-based cricothyroidotomy simulator to
      address these problems.

PMID- 15718751
TI  - The mini-screen: an innovative device for computer assisted surgery systems.
AB  - In this paper we focus on the design of Computer Assisted Surgery (CAS) systems
      and more generally Augmented Reality (AR) systems that assist a user in
      performing a task on a physical object. Digital information or new actions are
      defined by the AR system to facilitate or to enrich the natural way the user
      would interact with the real environment. We focus on the outputs of such
      systems, so that additional digital information is smoothly integrated with the
      real environment of the user, by considering an innovative device for displaying
      guidance information: the mini-screen. We first motivate the choice of the mini
      screen based on the ergonomic property of perceptual continuity and then present
      a design space useful to create interaction techniques based on a mini-screen.
      Two versions of a Computer ASsisted PERicardial (CASPER) puncture application, as
      well as a computer assisted renal puncture application, developed in our teams,
      are used to illustrate the discussion.

PMID- 15718752
TI  - Real-time visualization of cross-sectional data in three dimensions.
AB  - This paper describes a technique for viewing and interacting with 2-D medical
      data in three dimensions. The approach requires little pre-processing, runs on
      personal computers, and has a wide range of application. Implementation details
      are discussed, examples are presented, and results are summarized.

PMID- 15718753
TI  - Compressing different anatomical data types for the virtual soldier.
AB  - The Virtual Soldier Project endeavors to represent the baseline physiology and
      anatomy of a soldier using disparate but linked digital data types. Processing
      these data for storage, transmission and encryption requires different
      capabilities than are typical in a single codec. These representation and coding
      issues are illustrated and future directions are indicated.

PMID- 15718754
TI  - A real-time haptic interface for interventional radiology procedures.
AB  - Interventional Radiology (IR) is a minimally-invasive surgery technique (MIS)
      where guidewires and catheters are steered in the vascular system under X-ray
      imaging. In order to perform these procedures, a radiologist has to be correctly
      trained to master hand-eye coordination, instrument manipulation and procedure
      protocols. This paper proposes a computer-assisted training environment dedicated
      to IR. The system is composed of a virtual reality (VR) simulation of the anatomy
      of the patient linked to a robotic interface providing haptic force feedback.The
      paper focuses on the requirements, design and prototyping of a specific part of
      the haptic interface dedicated to catheters. Translational tracking and force
      feedback on the catheter is provided by two cylinders forming a friction drive
      arrangement. The whole friction can be set in rotation with an additional motor
      providing torque feedback. A force and a torque sensor are integrated in the
      cylinders for direct measurement on the catheter enabling disturbance
      cancellation with a close-loop force control strategy.

PMID- 15718755
TI  - An interactive simulation environment for craniofacial surgical procedures.
AB  - Recent advances in medical imaging and surgical techniques have made possible the
      correction of severe facial deformities and fractures. Surgical correction
      techniques often involve the direct manipulation - both relocation and surgical
      fracture - of the underlying facial bone. The work presented here introduces an
      environment for interactive, visuohaptic simulation of craniofacial surgical
      procedures, with an emphasis on both mandibular distraction procedures and
      traditional orthognathic surgeries. The simulator is intended both for
      instruction and for procedure-specific rehearsal, and can thus load canonical
      training cases or patient-specific image data into the interactive environment. A
      network module allows remote demonstration of procedure technique, a form of
      'haptic tutoring'. This paper discusses the simulation, haptic feedback, and
      graphic rendering techniques used to drive the environment. Particular emphasis
      is placed on techniques for fracture and subsequent rigid manipulation of bone
      structures, a key component of the relevant procedures.

PMID- 15718756
TI  - A GPU accelerated spring mass system for surgical simulation.
AB  - There is a growing demand for surgical simulators to do fast and precise
      calculations of tissue deformation to simulate increasingly complex morphology in
      real-time. Unfortunately, even fast spring-mass based systems have slow
      convergence rates for large models. This paper presents a method to accelerate
      computation of a spring-mass system in order to simulate a complex organ such as
      the heart. This acceleration is achieved by taking advantage of modern graphics
      processing units (GPU).

PMID- 15718757
TI  - Interactive 3D region extraction of volume data using deformable boundary object.
AB  - This study aims to establish an interactive and intuitive region extraction
      environment for volume data. A volume clipping method using deformable boundary
      object is proposed to support 3D region extraction task. Slice-based volume
      rendering of boundary elements enables to visualize clipped results in real time.
      Geometrical transformation and physics-based deformation support intuitive
      modification of 3D region of interest. Some extraction tasks are tested using CT
      data set on the developed system. All tests confirmed real-time visualization of
      clipped results is effective for interactive 3D region extraction in volume
      visualization and virtual object modeling.

PMID- 15718758
TI  - Virtual surgical telesimulations in otolaryngology.
AB  - Distance learning can be enhanced with the use of virtual reality; this paper
      describes the design and initial validation of a Web Environment for Surgery
      Skills Training on Otolaryngology (WESST-OT). WESST-OT was created aimed to help
      trainees to gain the skills required in order to perform the Functional
      Endoscopic Sinus Surgery procedure (FESS), since training centers and specialist
      in this knowledge are scarce in Colombia; also, it is part of a web based
      educational cycle which simulates the stages of a real procedure. WESST-OT is one
      from the WESST family of telesimulators which started to be developed from an
      architecture proposed at the Medicine Meets Virtual Reality conference 2002;
      also, it is a step towards the use of virtual reality technologies in Latin
      America.

PMID- 15718759
TI  - Emerging technologies for bioweapons defense.
AB  - The Global War on Terrorism (GWOT) has changed the way we think about national
      security. The tragic events of Sept.11 have shown us that world of the 21(st)
      century is clearly a dangerous place. Terrorism, more than ever, affects the very
      lives of each and every citizens of our country. Al Qaida has proven that it is
      able to use simple rudimentary methods to invoke strategic economic losses to our
      society with our own domestic resources as its weapons. The dawn of the new
      century has brought forth a new kind of asymmetric war where guerilla fighters
      are armed not with rifles but with technology at the touch of a keyboard. Warfare
      as we know it has changed and just as the military has its "transformation",
      medicine so too must have its own transformation in order to protect our citizen
      against the ever changing threat of bioterrorism. Virtual Reality and its
      applications can play a vital role in developing new countermeasures to minimize
      the catastrophic effects of a potential bioterror attack.

PMID- 15718760
TI  - Assessment of brain activities in immersive environments.
AB  - The primary goal of this study was to establish an objective baseline for
      subjects who participated in a study in an immersed environment created for the
      virtual reality therapy (VRT) situation. Since the effects of VRT on the subjects
      treated for neurosis have traditionally been measured by subjective measurements,
      there is a need to include objective measures. This will improve and validate the
      effectiveness of VRT. Fifteen college students participated in this study.
      Specifically, the researchers measured the activity of the subjects' brainwaves
      in response to the VRT using EEG technology. The preliminary data indicated that,
      in most cases, subjects had a decline in brain wave activity between what is
      deemed a normal / baseline brain activity and the brainwave activity recorded
      when they were when they were connected to the virtual reality equipment and
      under influence of an immersive scene. In rare instances, there were some
      subjects that showed extreme increases in brain activities. In addition, the data
      indicated that, in most cases, subjects are more relaxed while under the
      immersive influence with respect to brain activities than those that are not.

PMID- 15718761
TI  - Evaluation of 3D airway imaging of obstructive sleep apnea with cone-beam
      computed tomography.
AB  - This study evaluates the use of cone-beam Computer Tomography (CT) for imaging
      the upper airway structure of Obstructive Sleep Apnea (OSA) patients. The total
      airway volume and the anteroposterior dimension of oropharyngeal airway showed
      significant group differences between OSA and gender-matched controls, so if we
      increase sample size these measurements may distinguish the two groups. We
      demonstrate the utility of diagnosis of anatomy with the 3D airway imaging with
      cone-beam Computed Tomography.

PMID- 15718762
TI  - Multi-sensory surgical support system incorporating, tactile, visual and auditory
      perception modalities.
AB  - The incorporation of novel broad band sensory modalities, integrating tactile
      technology, with visual and auditory signals into the evolution of the next
      generation of surgical robotic is likely to significantly enhance their utility
      and safety. In this paper considerations are made of a system, where tactile
      information together with visual and audio feedback are integrated into a
      multisensory surgical support platform. The tactile sensor system uses a
      piezoelectric transducer (PZT) system to evaluate the haptic properties of
      tissues. The spatial position of the sensor is tracked by a video camera,
      visualizing the location of the marker. Tactile information is additionally
      converted to an audio signal, to represent tissue properties in terms of a
      frequency/amplitude modulated signal. Representative data were obtained from
      biological tissues demonstrating that the technology developed has potential
      applications in virtual systems or robotic tele-medical care. In view of these
      technical developments, consideration is made as to whether visual audio and
      tactile modalities act as independent sources of information.

PMID- 15718763
TI  - Estimation of dislocation after total hip arthroplasty by 4-dimensional.
AB  - We constructed a 4-dimensional musculoskeletal model for patients who have
      undergone total hip arthroplasty (THA), which aimed to simulate the movement of
      the patient's inner body structure and estimate the complications that can arise
      with THA. The model reflects patient-specific characteristics of the bone
      geometry, implant alignment and hip movement. In order to estimate the direction
      of the muscle force and the length of the muscles, we developed a string-type
      muscle model that represents the route of the muscles. The strings expand and
      contract according to the movement of the origin and insertion location of the
      muscle. We developed models for the seven muscles related to movement of the hip
      joint. By using this model, clinicians will be able to predict the possibility of
      dislocation or recognize the actual causes of dislocation, as well as any
      possible influences the muscle may have on dislocation.

PMID- 15718764
TI  - BrainTrain: brain simulator for medical VR application.
AB  - The brain is known as the most complex organ in the human body. Due to its
      complexity, learning and understanding the anatomy and functions of the cerebral
      cortex without effective learning assistance is rather difficult for medical
      novices and students in health and biological sciences. In this paper, we present
      a new virtual reality (VR) simulator for neurological education and neurosurgery.
      The system is based on a new three-dimensional (3D) user-computer interface
      design with a tangible object and a force-torque sensor. The system is combined
      with highly interactive computer-generated graphics and acoustics to provide
      multi-modal interactions through the user's sensory channels (vision, tactile,
      haptic and auditory). The system allows the user to feel the simulated object
      from its physical model that formed the interface device, while exploring or
      interacting with the mimicked computer-generated object in the virtual
      environment (VE). Unlike other passive interface devices, our system can detect
      the position and orientation of the interacting force in real-time, based on the
      system's set-up and a force-torque data acquisition technique. As long as the
      user is touching the model, the positions of the user's fingertip in the VE can
      be determined and is synchronized with the finger's motion in the physical world
      without requirement of an additional six-degree-of-freedom tracking device. The
      prior works have shown the use of the system set-up in medical applications. We
      demonstrate the system for neurological education and neurosurgery as a recent
      application. The main functions of the simulator contribute to education in
      neuroanatomy and visualization for diagnostic and pre-surgery planning. Once the
      user has touched the model, the system will mark the associated anatomy region
      and will provide the information of the region in terms of text note and/or
      sound. The user can switch from anatomy to the brain's function module, which
      will give details of motor, sensory or other cortical functions associated to the
      touch areas. In addition, the user can generate and visualize arbitrary cross
      sectional images from corresponding to the magnetic resonance imaging (MRI)
      datasets either for training or for diagnostic purpose. The user can manipulate
      the cross-section image interactively and intuitively by moving the finger on the
      interface device.

PMID- 15718766
TI  - Immersive visualization training of radiotherapy treatment.
AB  - External radiation beam treatment of cancer tumours involves delivery of
      invisible radiation beams through the body where internal structures can not be
      seen. Beam targeting of patient anatomy has to very accurate to achieve the
      desired therapeutic result. Good understanding of radiotherapy treatment (RT)
      concepts is essential to training. This paper presents a virtual environment
      simulator developed by the authors for training and education of intensity
      modulated radiotherapy (IMRT) treatment of cancer. This simulator employs
      immersive visualization to provide a high fidelity spatial awareness of the
      complex relationships between tumour, organs at risk, treatment beam and
      radiation dose. All these visualization are provided by a 3D virtual environment
      based on the patient in a RT treatment room. Immersive visualization using this
      simulator is being used to train radiation oncologist and radiation physicists
      about radiotherapy treatment.

PMID- 15718765
TI  - Smart tutor: a pilot study of a novel adaptive simulation environment.
AB  - Computer-based learning environments create the possibility of dynamic adaptation
      to address learner capabilities and user performance. Software algorithms, code
      named Smart Tutor, for motor skill learning were developed and applied to an
      abstract environment for laparoscopic surgery (RapidFire). Smart Tutor
      dynamically adjusts the environment to minimize frustration and optimize learning
      conditions for all learners. This study compared the first generation RapidFire /
      Smart Tutor (RF / ST) to the Minimal Invasive Surgery Trainer Virtual Reality
      (MIST VR) system for laparoscopic performance improvement and level of
      frustration. Two groups of novice laparoscopic learners were assessed by pre- and
      post- training paper cutting exercise and subjective surveys. Users of both
      systems showed improvement of laparoscopic skills as measured by the paper
      cutting exercises. No differences were shown between groups for level of
      improvement. However, a significant difference was seen in the subjective ratings
      on the post-training survey with less frustration for the RF / ST training group.
      Important information was acquired for refinements of the Smart Tutor algorithms.

PMID- 15718767
TI  - Toward in vivo mobility.
AB  - Today's laparoscopic tools impose severe ergonomic limitations and are
      constrained to only four degrees of freedom. These constraints limit the
      surgeon's ability to orient the tool tips arbitrarily, and can contribute to a
      variety of complications. Robots external to the patient have been used to aid in
      the manipulation of the tools and improve dexterity. However, these robots are
      expensive, bulky, and are used for only select procedures. In vivo robotic
      assistants have the potential to enhance the capabilities of the surgeon, reduce
      costs, and reduce patient trauma. The motion of these in vivo robots will not be
      constrained by the insertion incisions. Such assistants will need to attain
      optimal viewing angles by traversing the abdominal organs without causing trauma.
      This paper presents an experimental analysis of miniature in vivo robot wheels.

PMID- 15718768
TI  - E-learning experience: a teaching model with undergraduate surgery students in a
      developing country.
AB  - Colombian medical students do not have an effective approach to electronic
      facilities in situ or at home, in contrast with most of American and European
      medical programs. Our aim is to help medical students to handle current
      biomedical data, specifically surgical information, in the benefit of patients,
      themselves and the community via ICT. The model implemented as a pilot study had
      a good acceptance amongst undergraduate surgery students and faculty.

PMID- 15718769
TI  - Development of a VR therapy application for Iraq war military personnel with
      PTSD.
AB  - Post Traumatic Stress Disorder (PTSD) is reported to be caused by traumatic
      events that are outside the range of usual human experiences including (but not
      limited to) military combat, violent personal assault, being kidnapped or taken
      hostage and terrorist attacks. Initial data suggests that 1 out of 6 returning
      Iraq War military personnel are exhibiting symptoms of depression, anxiety and
      PTSD. Virtual Reality (VR) exposure therapy has been used in previous treatments
      of PTSD patients with reports of positive outcomes. The aim of the current paper
      is to specify the rationale, design and development of an Iraq War PTSD VR
      application that is being created from the virtual assets that were initially
      developed for theX-Box game entitled Full Spectrum Warrior which was inspired by
      a combat tactical training simulation, Full Spectrum Command.

PMID- 15718770
TI  - The LapSim: a learning environment for both experts and novices.
AB  - BACKGROUND: Simulated environments present challenges to both clinical experts
      and novices in laparoscopic surgery. Experts and novices may have different
      expectations when confronted with a novel simulated environment. The LapSim is a
      computer-based virtual reality laparoscopic trainer. Our aim was to analyze the
      performance of experienced basic laparoscopists and novices during their first
      exposure to the LapSim Basic Skill set and Dissection module. METHODS:
      Experienced basic laparoscopists (n=16) were defined as attending surgeons and
      chief residents who performed >30 laparoscopic cholecystectomies. Novices (n=13)
      were surgical residents with minimal laparoscopic experience. None of the
      subjects had used a computer-based laparoscopic simulator in the past. Subjects
      were given one practice session on the LapSim tutorial and dissection module and
      were supervised throughout the testing. Instrument motion, completion time, and
      errors were recorded by the LapSim. A Performance Score (PS) was calculated using
      the sum of total errors and time to task completion. A Relative Efficiency Score
      (RES) was calculated using the sum of the path lengths and angular path lengths
      for each hand expressed as a ratio of the subject's score to the worst score
      achieved among the subjects. All groups were compared using the Kruskal-Wallis
      and Mann-Whitney U-test. RESULTS: Novices achieved better PS and/or RES in
      Instrument Navigation, Suturing, and Dissection (p<0.05). There was no difference
      in the PS and RES between experts and novices in the remaining skills.
      CONCLUSION: Novices tended to have better performance compared to the experienced
      basic laparoscopists during their first exposure to the LapSim Basic Skill set
      and Dissection module.

PMID- 15718771
TI  - A novel drill set for the enhancement and assessment of robotic surgical
      performance.
AB  - BACKGROUND: There currently exist several training modules to improve performance
      during video-assisted surgery. The unique characteristics of robotic surgery make
      these platforms an inadequate environment for the development and assessment of
      robotic surgical performance. METHODS: Expert surgeons (n=4) (>50 clinical
      robotic procedures and >2 years of clinical robotic experience) were compared to
      novice surgeons (n=17) (<5 clinical cases and limited laboratory experience)
      using the da Vinci Surgical System. Seven drills were designed to simulate
      clinical robotic surgical tasks. Performance score was calculated by the equation
      Time to Completion + (minor error) x 5 + (major error) x 10. The Robotic Learning
      Curve (RLC) was expressed as a trend line of the performance scores corresponding
      to each repeated drill. RESULTS: Performance scores for experts were better than
      novices in all 7 drills (p<0.05). The RLC for novices reflected an improvement in
      scores (p<0.05). In contrast, experts demonstrated a flat RLC for 6 drills and an
      improvement in one drill (p=0.027). CONCLUSION: This new drill set provides a
      framework for performance assessment during robotic surgery. The inclusion of
      particular drills and their role in training robotic surgeons of the future
      awaits larger validation studies.

PMID- 15718772
TI  - Spherical mechanism analysis of a surgical robot for minimally invasive surgery -
      analytical and experimental approaches.
AB  - Recent advances in technology have led to the fusion of MIS techniques and robot
      devices. However, current systems are large and cumbersome. Optimizing the
      surgical robot mechanism will eventually lead to its integration into the
      operating room (OR) of the future becoming the extended presence of the surgeon
      and nurses in a room occupied by the patient alone. By optimizing a spherical
      mechanism using data collected in-vivo during MIS procedures, this study is
      focused on a bottom-up approach to developing a new class of surgical robotic
      arms while maximizing their performance and minimizing their size. The spherical
      mechanism is a rotational manipulator with all axes intersecting at the center of
      the sphere. Locating the rotation center of the mechanism at the MIS port makes
      this class of mechanism a suitable candidate for the first two links of a
      surgical robot for MIS. The required dexterous workspace (DWS) is defined as the
      region in which 95% of the tool motions are contained based on in-vivo
      measurements. The extended dexterous workspace (EDWS) is defined as the entire
      abdominal cavity reachable by a MIS instruments. The DWS is defined by a right
      circular cone with a vertex angle of 60 degrees and the EDWS is defined by a cone
      with an elliptical cross section created by two orthogonal vertex angles of 60
      degrees and 90 degrees. A compound function based on the mechanism's isotropy and
      the mechanism stiffness was considered as the performance metric cost function.
      Optimization across both the DWS and the EDWS lead to a serial mechanism
      configuration with link length angles of 74 degrees and 60 degrees for a serial
      configuration. This mechanism configuration maximized the kinematic performance
      in the DWS while keeping the EDWS as its reachable workspace. Surgeons, using a
      mockup of two mechanisms in a MIS setup, validated these results experimentally.
      From these experiments the serial configuration was deemed most applicable for
      MIS robotic applications compared to a parallel mechanism configuration. The
      mechanical design of a cable actuated surgical robot was based on optimized link
      length angles. The system is currently being integrated into a fully operated two
      arm system. Small form-factor surgical robotic arms with optimized dexterous
      workspaces will facilitate the integration of multiple arms while avoiding self
      collision in the OR of the future.

PMID- 15718773
TI  - Using an ontology of human anatomy to inform reasoning with geometric models.
AB  - The Virtual Soldier project is a large effort on the part of the U.S. Defense
      Advanced Research Projects agency to explore using both general anatomical
      knowledge and specific computed tomographic (CT) images of individual soldiers to
      aid the rapid diagnosis and treatment of penetrating injuries. Our goal is to
      develop intelligent computer applications that use this knowledge to reason about
      the anatomic structures that are directly injured and to predict propagation of
      injuries secondary to primary organ damage. To accomplish this, we needed to
      develop an architecture to combine geometric data with anatomic knowledge and
      reasoning services that use this information to predict the consequences of
      injuries.

PMID- 15718774
TI  - Assessing surgical skill training under hazardous conditions in a virtual
      environment.
AB  - The present study examined the performance of a surgical procedure under
      simulated combat conditions. Eleven residents performed a cricothyroidotomy on a
      mannequin-based simulator in a fully immersive virtual environment running a
      combat simulation with a virtual sniper under both day and night time lighting
      conditions. The results showed that completion times improved between the first
      and second attempt and that differences between day and night time conditions
      were minimal. However, three participants were killed by the virtual sniper
      before completing the procedure. These results suggest that some participants'
      ability to allocate attention to the task and their surroundings was
      inappropriate even under simulated hazardous conditions. Further, this study
      shows that virtual environments offer the chance to study a wider variety of
      medical procedures performed under an unlimited number of conditions.

PMID- 15718775
TI  - An automatic robust meshing algorithm for soft tissue modeling.
AB  - Soft tissue simulation with the finite element method is based on discretizations
      of anatomical objects. The structure of organs is mostly heterogeneous. To
      compute the deformation of composite materials correctly borders between adjacent
      tissues must be preserved. In this paper a new meshing algorithm is presented
      that fulfill this requirement. Additionally it works automatically in a straight
      forward manner to produce high quality 3d meshes from input triangle surfaces.
      The algorithm shows robust behavior and allows even to generate mesh from the
      most complex geometries. The processing time depends directly on the size of the
      input mesh and not on topology. This makes this algorithm calculable hence useful
      for time dependent cases, for example to adapt intraoperatively to modified
      operation status.

PMID- 15718776
TI  - Visualizing volumetric data sets using a wireless handheld computer.
AB  - We describe two extensions to the Nomadic Anatomy Viewer application that both
      make use of a statistical clustering analysis. In the first case the results of
      clustering are used to identify the geometry of the local neighborhood and
      provide for automated navigation along structures. In the second case the
      analysis is used to support a pen-based interface for interactively rendering
      selected portions of a volumetric data set.

PMID- 15718777
TI  - Quantifying risky behavior in surgical simulation.
AB  - Evaluating a trainee's performance on a simulated procedure involves determining
      whether a specified objective was met while avoiding certain "injurious" actions
      that damage vulnerable structures. However, it is also important to teach the
      stylistic behaviors that minimize overall risk to the patient, even though these
      criteria may be more difficult to explicitly specify and detect. In this paper,
      we address the development of metrics that evaluate the risk in a trainee's
      behavior while performing a simulated mastoidectomy. Specifically, we measure the
      trainee's ability to maintain an appropriate field of view so as to avoid
      drilling bone that is hidden from view, as well as to consistently apply
      appropriate forces and velocities. Models of the maximum safe force and velocity
      magnitudes as functions of distances from key vulnerable structures are learned
      from model procedures performed by an expert surgeon on the simulator. In
      addition to quantitatively scoring the trainee's performance, these metrics allow
      for interactive 3D visualization of the performance by distinctive coloring of
      regions in which excessive forces or velocities were applied or insufficient
      visibility was maintained, enabling the trainee to pinpoint his/her mistakes and
      how to correct them. Although these risky behaviors relate to a mastoidectomy
      simulator, the objectives of maintaining visibility and applying safe forces and
      velocities are common in surgery, so it may be possible to extend much of this
      methodology to other procedures.

PMID- 15718778
TI  - Haptic herniorrhaphy simulation with robust and fast collision detection
      algorithm.
AB  - Collision detection and soft tissue deformation are two major research challenges
      in real time VR based simulation, especially when haptic feedback is required. We
      have developed a real time collision detection algorithm for a prototype
      laparoscopic surgery trainer. However, this algorithm makes no assumptions about
      its applications and thus can be a generic solution to complicated collision
      detection problems. For soft tissue modeling, we use the mass-spring model
      enhanced with volume constraint and, stability control methods. We use both the
      new collision detection and tissue modeling algorithms in a bimanual hernia
      repair simulator which performs a mesh prosthesis stapling operation in real
      time.

PMID- 15718779
TI  - Affordable virtual environments: building a virtual beach for clinical use.
AB  - Virtual Reality has been used for clinical application for about 10 years and has
      proved to be an effective tool for treating various disorders. In this paper, we
      want to share our experience in building a 3D, motion tracked, immersive VR
      system for pain treatment and biofeedback research.

PMID- 15718780
TI  - Analysis of masticatory muscle condition using the 4-dimensional muscle model for
      a patient with square mandible.
AB  - The present study was conducted to ascertain characteristics of mandibular
      movements in patients with SQM, observe the kinetics of masticatory muscles using
      a four-dimensional (4D) muscle model, and kinetically investigate the etiology of
      Square Mandible (SQM). As results, 1, In the maximum opening position, location
      of the condyle was beyond the articular tubercle for volunteer, but within the
      mandibular fossa for SQM patient. 2, While the temporal muscle of volunteer was
      markedly expanded, that of SQM patient was not. 3, In both volunteer and SQM
      during left lateral excursion, the right mandibular condyle moved to a position
      slightly before the lowest point of the articular tubercle. The 4D muscle model
      showed that the cause of limited mouth opening in SQM patient was insufficient
      expansion of the temporal muscle, and not dysfunction of the opening muscles.
      Insufficient expansion of the temporal muscle stresses the masseter muscle and
      leads to hypertrophy of the masseter muscle and hyperplasia of the mandibular
      angle, resulting in the unique facial configuration.

PMID- 15718781
TI  - Automated renderer for visible human and volumetric scan segmentations.
AB  - Creating a library of binary segmentation mask sequences for the abdominal
      anatomy hierarchy of SNOMED and developing a quick, flexible automatic method for
      generating iso-surface models from these named structure masks has been a primary
      goal in our research. This paper describes our development of a clear path for
      computing visualizations of arbitrary groups of organs from these masks
      (typically generated from Visible Human data). One use of these methods is
      teaching the anatomy of various organ systems in the human body using virtual
      reality environments.

PMID- 15718782
TI  - Distributed collaborative radiological visualization using access grid.
AB  - This paper describes early technical success toward enabling high quality
      distributed shared volumetric visualization of radiological data in concert with
      multipoint video collaboration using Grid infrastructures. Key principles are the
      use of commodity off-the-shelf hardware for client machines and open source
      software to permit deployment of over a large and diverse group of sites. Key
      software used includes the Access Grid Toolkit, the Visualization Toolkit, and
      Chromium.

PMID- 15718783
TI  - Development of a method for surface and subsurface modeling using force and
      position sensors.
AB  - Subsurface modeling of deformable objects, such as soft tissues and organs,
      involves the use of non-destructive methods of determining the properties of an
      object encased by a material. Some of the properties that can be determined from
      subsurface modeling include: shape, hardness, texture and possibly material. The
      ability to determine these properties is based on the accuracy of the method used
      and the properties of the surface encasing the object. As computers become more
      powerful and are able to produce even more realistic graphics, it will be
      possible to store and re-create precise duplicates of the original for later
      analysis. This paper will present a method of approximately modeling both the
      surface and an object below the surface of the skin by a method of palpation and
      then present this data in an interactive 3-D model.

PMID- 15718784
TI  - The physiology and pharmacology of growing old, as shown in body simulation.
AB  - Geriatric medicine is becoming increasingly important, due to the aging of our
      population. Healthcare givers need methods that can teach efficiently and
      painlessly the complexities involved with aging. One important tool in this area
      comprises modeling and simulation. Accordingly, we present a detailed model and
      simulation of the aging process. To implement the aging process, we changed over
      50 existing parameters that are part of a physiologic, pharmacologic multiple
      transport model of the human body. To evaluate the new patients, we imposed three
      stresses: anesthesia induction, hemorrhage and apnea. Five patients were used: a
      young healthy patient and four healthy, but elderly, patients, aged 65, 75, 85
      and 95 years. We observed an age-related response to the stresses. The elderly
      patients fared worse with anesthetic induction and with hemorrhage, but better
      with apnea. Some independent data support our results.

PMID- 15718785
TI  - Physiologic and chemical simulation of cyanide and sarin toxicity and therapy.
AB  - The possibility of mass terrorism has become increasingly apparent. Accurate and
      relevant teaching tools are needed for healthcare givers and emergency personnel
      of all experience. We describe one of these tools, BODY Simulation, and its use
      in training caregivers to respond to chemical terrorism. We have implemented two
      chemical agents--cyanide and sarin, the latter a nerve agent--in a detailed whole
      body model and simulation. In the simulation, each agent was administered to a
      healthy young adult, first without therapy, then with therapy, for a total of
      four runs. We recorded several variables, each appropriate to the agent used. The
      recorded variables included physiological variables in addition to the blood and
      brain concentrations of each agent and its antidotes. In addition, for cyanide,
      the compounds that resulted as the byproducts of therapy (methemoglobin, for
      example) were plotted. The results were consistent with those described in the
      literature, including agent concentrations and pathophysiologic changes.

PMID- 15718786
TI  - Monitor height affects surgeons' stress level and performance on minimally
      invasive surgery tasks.
AB  - This study investigated the effect of monitor height on surgeons' workload and
      performance during simulated minimally invasive surgery (MIS). Fourteen volunteer
      subjects (7 experienced, 7 inexperienced) performed a cutting task in a training
      box at a standard MIS station with the video monitor positioned in random order
      at, below (-35 degrees), and above (+15 degrees) the subject's eye level. Task
      time and error, difficulty and discomfort, head orientation, trapezius and neck
      muscle activity, and skin conductance were recorded. The experienced subjects
      performed the task faster, with less error, and with less difficulty than did the
      inexperienced subjects. For the experienced subjects, error decreased when the
      monitor was lowered. Difficulty and discomfort increased at the high monitor
      position. As the monitor was lowered, the head pitched forward, and paraspinal
      cervical muscle activity increased. Variability in sternocleidomastoid activity
      increased both at the low and high monitor positions. The results show that
      monitor height affects both performance and workload. The monitor should be
      lowered to reduce error and task difficulty but not so low as to produce
      excessive neck flexion.

PMID- 15718787
TI  - A new platform for laparoscopic training and education.
AB  - A new platform for laparoscopic training and education is presented. Fundamental
      requirements about a flexible haptic interface, specter of training areas, skill
      assessment, educational content, and level of realism are presented and
      discussed. The new system, including a new and flexible haptic interface and a
      broad specter of training modules combined with the use of multimedia content, is
      described.

PMID- 15718788
TI  - Virtual reality testing of multi-modal integration in schizophrenic patients.
AB  - Our goal is to develop a new family of automatic tools for the diagnosis of
      schizophrenia, using Virtual Reality Technology (VRT). VRT is specifically
      suitable for this purpose, because it allows for multi-modal stimulation in a
      complex setup, and the simultaneous measurement of multiple parameters. In this
      work we studied sensory integration within working memory, in a navigation task
      through a VR maze. Along the way subjects pass through multiple rooms that
      include three doors each, only one of which can be used to legally exit the room.
      Specifically, each door is characterized by three features (color, shape and
      sound), and only one combination of features -- as determined by a transient
      opening rule -- is legal. The opening rule changes over time. Subjects must learn
      the rule and use it for successful navigation throughout the maze. 39
      schizophrenic patients and 21 healthy controls participated in this study. Upon
      completion, each subject was assigned a performance profile, including various
      error scores, response time, navigation ability and strategy. We developed a
      classification procedure based on the subjects' performance profile, which
      correctly predicted 85% of the schizophrenic patients (and all the controls). We
      observed that a number of parameters showed significant correlation with standard
      diagnosis scores (PANSS), suggesting the potential use of our measurements for
      future diagnosis of schizophrenia. On the other hand, our patients did not show
      unusual repetition of response despite stimulus cessation (called perseveration
      in classical studies of schizophrenia), which is usually considered a robust
      marker of the disease. Interestingly, this deficit only appeared in our study
      when subjects did not receive proper explanation of the task.

PMID- 15718789
TI  - Emotional and performance attributes of a VR game: a study of children.
AB  - In this paper we present the results of a study to determine the effect and
      efficacy of a Virtual Reality game designed to elicit movements of the upper
      extremity. The study is part of an on-going research effort to explore the use of
      Virtual Reality as a means of improving the effectiveness of therapy for children
      with motor impairments. The current study addresses the following questions: 1.
      Does a VR game requiring repetitive motion sufficiently engage a child? 2. Are
      there detrimental physiological or sensory side-effects when a child uses an HMD
      based VR? 3. Are the movements produced by a child while playing a VR game
      comparable to movements produced when carrying out a similar task in the real
      world? Based on study results, the enjoyment level for the game was high. ANOVA
      performed on the results for physical well-being pre- and post-VR showed no
      overall ill-effects as perceived by the children. Playing the game did not effect
      proprioception based on pre- and post-VR test scores. Motion data show similar,
      but not identical, overall movement profiles for similar tasks performed in the
      real and virtual world. Motor learning occurs in both environments, as measured
      by time to complete a game cycle.

PMID- 15718790
TI  - Virtual reality training improves students' knowledge structures of medical
      concepts.
AB  - Virtual environments can provide training that is difficult to achieve under
      normal circumstances. Medical students can work on high-risk cases in a
      realistic, time-critical environment, where students practice skills in a
      cognitively demanding and emotionally compelling situation. Research from
      cognitive science has shown that as students acquire domain expertise, their
      semantic organization of core domain concepts become more similar to those of an
      expert's. In the current study, we hypothesized that students' knowledge
      structures would become more expert-like as a result of their diagnosing and
      treating a patient experiencing a hematoma within a virtual environment. Forty
      eight medical students diagnosed and treated a hematoma case within a fully
      immersed virtual environment. Student's semantic organization of 25 case-related
      concepts was assessed prior to and after training. Students' knowledge structures
      became more integrated and similar to an expert knowledge structure of the
      concepts as a result of the learning experience. The methods used here for
      eliciting, representing, and evaluating knowledge structures offer a sensitive
      and objective means for evaluating student learning in virtual environments and
      medical simulations.

PMID- 15718791
TI  - Emphatic, interactive volume rendering to support variance in user expertise.
AB  - Various levels of representation, from abstract to schematic to realistic, have
      been exploited for millennia to facilitate the transfer of information from one
      individual to another. Learning complex information, such as that found in
      biomedicine, proves specifically problematic to many, and requires incremental,
      step-wise depictions of the information to clarify structural, functional, and
      procedural relationships.Emerging volume-rendering technique, such as non
      photorealistic representation, coupled with advances in computational speeds,
      especially new graphical processing units, provide unique capabilities to explore
      the use of various levels of representation in interactive sessions. We have
      developed a system that produces images that simulate pictorial representations
      for both scientific and biomedical visualization. The system combines traditional
      and novel volume illustration techniques. We present examples from our efforts to
      distill representational techniques for both creative exploration and emphatic
      presentation for clarity. More specifically, we present our efforts to adapt
      these techniques for interactive simulation sessions being developed in a
      concurrent project for resident training in temporal bone dissection simulation.
      The goal of this effort is to evaluate the use of emphatic rendering to guide the
      user in an interactive session and to facilitate the learning of complex
      biomedical information, including structural, functional, and procedural
      information.

PMID- 15718792
TI  - First clinical tests with the augmented reality system INPRES.
AB  - In this paper we present the results of the first patient experiment in
      craniofacial surgery of the INPRES system - an augmented reality system on the
      basis of a tracked see-through head-mounted display.

PMID- 15718793
TI  - Construction of a high-tech operating room for image-guided surgery using VR.
AB  - This project aimed to construct an operating room to implement high dimensional
      (3D, 4D) medical imaging and medical virtual reality techniques that would enable
      clinical tests for new surgical procedures. We designed and constructed such an
      operating room at Dai-san Hospital, the Jikei Univ. School of Medicine, Tokyo,
      Japan. The room was equipped with various facilities for image-guided, robot and
      tele- surgery. In this report, we describe an outline of our "high-tech operating
      room" and future plans.

PMID- 15718794
TI  - Tele-surgical simulation system for training in the use of da Vinci surgery.
AB  - Laparoscopic surgery including robotic surgery allows the surgeon to be able to
      conduct minimally invasive surgery. A surgeon is required to master difficult
      skills for this surgery to compensate for the narrow field of view, limitation of
      work space, and the lack of depth sensation. To counteract these drawbacks, we
      have been developing a training simulation system that can allow surgeons to
      practice and master surgical procedures. In addition, our system aims to
      distribute a simulation program, to provide a means of collaboration between
      remote hospitals, and to be able to provide a means for guidance from an expert
      surgeon. In this paper, we would like to show the surgery simulation for da Vinci
      surgery, in particular a cholecystectomy. The integral parts of this system are a
      soft tissue model which is created by the sphere-filled method enabling real-time
      deformations based on a patient's data, force feedback devices known as a PHANToM
      and the Internet connection. By using this system a surgeon can perform surgical
      maneuvers such as pushing, grasping, and detachment in real-time manipulation.
      Moreover, using the broadband communication, we can perform the tele-surgical
      simulation for training.

PMID- 15718795
TI  - Homeland security and virtual reality: building a Strategic Adaptive Response
      System (STARS).
AB  - The advent of the Global War on Terrorism (GWOT) underscored the need to improve
      the U.S. disaster response paradigm. Existing systems involve numerous agencies
      spread across disparate functional and geographic jurisdictions. The current
      architecture remains vulnerable to sophisticated terrorist strikes. To address
      these vulnerabilities, we must continuously adapt and improve our Homeland
      Security architecture. Virtual Reality (VR) technologies will help model those
      changes and integrate technologies. This paper provides a broad overview of the
      strategic threats, together with a detailed examination of how specific VR
      technologies could be used to ensure successful disaster responses.

PMID- 15718796
TI  - Haptic interaction and visualization of elastic deformation.
AB  - In this paper, we represent a new method to model real-time local and global
      deformations on a variety of three-dimensional sculptured surfaces governed by
      physical principles. The deformable objects are highly elastic with linear
      behavior in the range of typical haptic forces. A deformation model is developed
      for incompressible material based on a mapping technique and the superposition
      principle. The law of energy conservation is used to calculate real-time force
      reflection. Using the divergence theorem, force reflection is calculated for
      volumetric deformations.

PMID- 15718797
TI  - Segmenting deformable surface models using haptic feedback.
AB  - Clinically relevant segmentation often incorporates physician insight in the
      segmentation process (eg. overestimation of tumors). This is a primary reason in
      the continued use of per-slice based segmentation approaches. Segmenting
      structures directly by interacting with a volume space provides the advantages of
      being time efficient and accurate in contrast to per-slice based methods. In this
      approach volume navigation and parameter specification become critical towards
      the accuracy of the results obtained. In this paper we present some preliminary
      results in our research towards segmentation using a haptic device for navigation
      and parameter specification in an immersive environment. To incorporate the
      physician's requirements we model the results as a deformable surface model and
      the user interacts with the surface to obtain the final segmentation.

PMID- 15718798
TI  - Parametric model of the scala tympani for haptic-rendered cochlear implantation.
AB  - A parametric model of the human scala tympani has been designed for use in a
      haptic-rendered computer simulation of cochlear implant surgery. It will be the
      first surgical simulator of this kind. A geometric model of the Scala Tympani has
      been derived from measured data for this purpose. The model is compared with two
      existing descriptions of the cochlear spiral. A first approximation of the
      basilar membrane is also produced. The structures are imported into a force
      rendering software application for system development.

PMID- 15718799
TI  - Three dimensional electromechanical model of porcine heart with penetrating wound
      injury.
AB  - The aim of this study is development a prototype computational model of the pig
      heart that can be used to predict physiological responses to a penetrating wound
      injury. The pig has been chosen for this model studies because it shares many
      anatomical similarities with humans. Three-dimensional cubic Hermite finite
      element meshes based on detailed measurements of porcine anatomy combined into an
      integrated anatomic model. The pig ventricular model includes detailed left and
      right ventricular geometry and myofiber and laminar sheet orientations throughout
      the mesh. The cardiac mesh was refined and monodomain equations for action
      potential propagation solved using well-established collocation-Galerkin finite
      element methods. The membrane kinetic equations for the action potential model
      was based on detailed cellular models of transmembrane ionic fluxes and
      intracellular calcium fluxes in canine ventricular myocytes and human atrial
      myocytes. We modified the anisotropic myocardial conductivity tensor on the
      endocardial surface of the ventricles by making use of a surface model fitted to
      measured of Purkinje fiber network anatomy. The mechanical model compute regional
      three-dimensional stress and strain distributions using anisotropic constitutive
      laws referred to local material coordinate axes defined by local myofiber and
      laminar sheet orientations. Passive myocardial mechanics modeled using
      exponential orthotropic strain energy functions. Active systolic myocardial
      stresses computed from a multi-scale model that uses crossbridge theory to
      predict calcium-activated sarcomere length- and velocity-dependent tension
      filament tension. Since the electrical and mechanical models use a common finite
      element mesh as the parent parametric framework and both models are solved within
      our custom finite element package, it is straightforward to couple these models,
      as we have recently done for a model of coupled ventricular electromechanics. We
      apply the coupled electromechanical model to predict alterations in regional
      diastolic and systolic wall mechanics associated with rhythm disturbances and
      possible arrhythmias with decreased blood volume, tamponade, myocardial injury,
      and regional ischemia caused by a penetrating wound.

PMID- 15718800
TI  - Beyond VR: creating the augmented physician.
AB  - The ongoing shift of high tech capability from the specialist to the primary
      physician and the merging of medical and surgical therapies will demand more
      sophisticated measurement and control, but more positively, it will be possible
      to differentiate each individual situation and tailor treatment to provide an
      optimum result for each person, for each condition, in each environment, if these
      could all be measured, understood, and effected. The effective augmentation of
      the caregiver's physical, sensory, and cognitive capabilities will require more
      transparent, nuanced, and adaptive interfaces to information and to its
      therapeutic application. While the enhancement and classification of digitized
      findings is a beginning, the key may be better tracking and presentation of the
      chronological course, particularly the prior events which set the physiologic or
      morphologic data in context. Systems engineering approaches will define paths
      toward optimized, autonomous treatment, where the most rapid progress may be made
      through functional partitioning using scale-independent models, and the
      delineation of intermediate stages between today's macroscopic presentation of
      disease and molecular-scale treatment. These stages will comprise the steps
      toward useful patient avatars; our task is to fill in, with successively more
      powerful models, the convergence of large scale and small scale information, as
      it is used to support diagnostic and therapeutic decisions.

PMID- 15718801
TI  - Stiffness and texture perception for teledermatology.
AB  - The goal of the teledermatology project currently being carried out at Stanford
      University is to deliver tactile images of the human skin to a dermatologist at a
      remote location, in real time. In order to make a diagnosis, dermatologists
      typically need to obtain data regarding the skin texture and the mechanical
      properties of any lesions on a patient's skin. For example, pre-cancerous or
      weather-damaged skin typically feels rougher than normal skin and the profile and
      stiffness of the underlying tissue may shed light on the nature of a skin
      disease.

PMID- 15718802
TI  - Linking human anatomy to knowledge bases: a visual front end for electronic
      medical records.
AB  - A new concept of a visual electronic medical record is presented based on
      developments ongoing in the Defense Advanced Research Projects Agency Virtual
      Soldier Project. This new concept is based on the holographic medical electronic
      representation (Holomer) and on data formats being developed to support this. The
      Holomer is being developed in two different visualization environments, one of
      which is suitable for prototyping the visual electronic medical record. The
      advantages of a visual approach as a front end for electronic medical records are
      discussed and specific implementations are presented.

PMID- 15718804
TI  - Using an approximation to the euclidean skeleton for efficient collision
      detection and tissue deformations in surgical simulators.
AB  - This paper describes a technique for efficient collision detection and
      deformation of abdominal organs in surgical simulation using an approximation of
      the Euclidean skeleton. Many researchers have developed surgical simulators, but
      one of the most difficult underlying problems is that of organ-instrument
      collision detection followed by the deformation of the tissue caused by the
      instrument. Much of the difficulty is due to the vast number of polygons in high
      resolution complex organ models. A high resolution gall bladder model for
      instance can number in the tens of thousands of polygons. Our methodology
      utilizes the reduction power of the skeleton to reduce computations. First, we
      recursively compute approximations to the Euclidean skeleton to generate a set of
      skeletal points for the organ. Then we pre-compute for each vertex in each
      polygon the associated skeleton point (minimal distance discs). A spring is then
      connected from each vertex to its associated skeleton point to be used in the
      deformation algorithm. The data structure for the organ thus stores for each
      skeletal point its maximum and minimum distances and the list of associated
      vertices. A heuristic algorithm using the skeleton structure of the instrument
      and the skeleton of the organ is used to determine instrument collisions with the
      organ.

PMID- 15718803
TI  - Simulating the continuous curvilinear capsulorhexis procedure during cataract
      surgery on the EYESI system.
AB  - This paper describes a technique for simulating the capsulorhexis procedure
      during cataract surgery on the EYESI system. The continuous curvilinear
      capsulorhexis technique can be a difficult procedure for beginning ophthalmology
      surgeons. In the initial phase of tearing the tissue, the tear vector is
      tangential to the circumference of the tear circle. However, without the proper
      re-grasping of the flap of torn tissue close to the tear point, the tear vector
      angle quickly runs downhill possibly causing severe damage to the tissue. Novice
      surgeons tend to try to complete the capsulorhexis without the time consuming re
      grasping of the tissue flap. Other factors such as anterior bowing of the lens
      diaphragm, patient age, and shallow anterior chambers add to the problematic
      nature of the procedure. The tissue area is modeled as a curvilinear mesh of
      nodes and springs. Deformation is accomplished via a physically based particle
      model utilizing a heuristic algorithm to constrain the deformation calculations
      to the locality of the tear area to speed up computations. The training software
      alerts the user of any potential tear problems before they occur thus instructing
      the novice surgeon. The EYESI hardware system (from VRMagic GmbH) provides the
      user with stereoscopic images thus providing 3D viewing. Our capsulorhexis
      simulator software models a number of tear problems and anomalies to provide a
      useful training environment without the dangers of using live patients.

PMID- 15718805
TI  - Virtual surgical planning and CAD/CAM in the treatment of cranial defects.
AB  - The purpose of this work was to enhance the clinical outcome in the neurosurgical
      treatment of cranial defects and fibrous dysplasia. Cranial defects require
      repair using a variety of materials to protect the brain and provide a good
      cosmetic outcome for the patient. Virtual neurosurgery and CAD/CAM techniques
      have been employed to increase the implant 3-dimensional accuracy. The source
      data was 3D Computed Tomography scans. The CT scans were visualised using surface
      shading and rotation with volume rotation and re-sizing being used to review the
      complete data set. The volume data was manipulated using 3D image editing and
      surface modelling. Physical models of the patients' skulls were created using
      computed numerical milling which provided a physically accurate template for the
      production of a cranial implant. This has led to improved fitting for titanium
      plates requiring less theatre time and in the case of fibrous dysplasia a change
      in the operative technique from a two stage operation to one stage.

PMID- 15718806
TI  - New approaches to computer-based interventional neuroradiology training.
AB  - For over 20 years, interventional methods have substantially improved the
      outcomes of patients with cardiovascular disease. However, these procedures
      require an intricate combination of visual and tactile feedback and extensive
      training periods. In this paper, a prototype of endovascular therapy training
      system is presented. A set of core simulation components applicable to most
      vascular procedures has been designed and integrated into a real-time high
      fidelity interventional neuroradiology training system for the prompt treatment
      of ischemic stroke. We believe it will improve the quality of training and the
      speed of learning without putting patients at risk.

PMID- 15718807
TI  - CAD generated mold for preoperative implant fabrication in cranioplasty.
AB  - Intraoperative fabrication of acrylic cranial implants may be difficult and will
      increase operation time. In addition forming implants directly on the defect,
      intracranial tissues are exposed to heat of polymerization and residual monomer,
      that occurs, when autopolymerizing methyl methacrylate is used intraoperatively.
      Furthermore the cosmetical result may be unacceptable. Preoperatively formed
      acrylic implants may reduce these disadvantages compared to conventional
      techniques in cranioplasty. We will present methods for preoperative fabrication
      of cranial implants for a cadaver specimen. Implants were fabricated using a
      Rapid prototyping (RP) models of the skull built by Fused Deposition Modeling
      (FDM). In addition a mold of the defect was generated by CAD techniques, that can
      serve as a template for implant design.

PMID- 15718808
TI  - Effect of binocular stereopsis on surgical manipulation performance and fatigue
      when using a stereoscopic endoscope.
AB  - We compared performance in three kinds of endoscopic tasks -- a pegboard,
      incision, and suturing - under the monoscopic (2D) and stereoscopic (3D) visual
      conditions conducted for 1 hour in total. We also evaluated the degree of fatigue
      from the aspects of subjective and objective consciousness using the critical
      flicker frequency (CFF) test together with a questionnaire of fatigue. A total of
      eight subjects showed higher performance when using the 3D display than the 2D
      display in all three tasks and, simultaneously, improvement in performance as a
      result of learning effect. No difference of fatigue was found depending on the
      display conditions both in the CFF test and questionnaire.

PMID- 15718809
TI  - A dynamic friction model for haptic simulation of needle insertion.
AB  - This paper describes a new friction model, termed the brush model, suitable for
      haptic simulations of needle insertion in virtual environments. A novel two-layer
      surface contact model is presented that provides real-time rendering of friction
      forces at haptic refresh rates. A significant modification to the brush model is
      also presented, leading to a new friction model, termed the fixed bristle brush
      model. Simulation results show that the two models can accurately reflect the
      experimentally observed friction characteristics. This paper presents a
      simulation of friction during needle insertion; results agree with the
      experimental observations.

PMID- 15718810
TI  - Enhanced pre-computed finite element models for surgical simulation.
AB  - Soft tissue modeling is an important component in effective surgical simulation
      systems. A pre-computed finite element method based on elastic models is well
      suited to modeling soft tissue deformation. This paper addresses two principal
      issues: the flexibility of the pre-computed FE method and the approximation
      approach to non-linear elastic models. We describe a dynamic mechanism of the
      reconfiguration of the contacted nodes and the fixed boundary, without re
      computing the inverse of the global stiffness matrix. The flexibility of the pre
      computed models is described for both linear and non-linear elastic models.

PMID- 15718811
TI  - Cardiac MR image segmentation and left ventricle surface reconstruction based on
      level set method.
AB  - A two-stage segmentation algorithm is presented to solve the problems of
      inhomogeneity, weak edges and artifacts exhibited in the magnetic resonance
      imaging (MRI) images. First, the K-mean clustering algorithm is applied to
      classify the objects. Then, a speed function based on the clustering results is
      defined in order to search the rough boundary. Secondly, a speed function of the
      gradient intensity is constructed to locate the boundary accurately. Due to the
      lack of deformation information of the boundaries between MR slices, a deformable
      model is used to reconstruct the shape of the LV: a dynamic equation governing
      the surface deformation is given; from the slice data, external forces are
      constructed and elastic forces are provided with mean curvatures of the
      deformation surface. The level set method is applied to solve the dynamic
      equation for the LV shape. Experimental results demonstrate the effectiveness of
      the algorithm listed in the paper.

PMID- 15718812
TI  - Medical treatments and cares for geriatric syndrome: new strategies learned from
      frail elderly.
AB  - In Japan, there are 21 million older people above 65 years, and about 8% of them
      are frail elderly. Geriatrics is to study the frail elderly as to why they become
      frail elderly, and to treat patients properly or the remaining 92% older people
      not to become frail elderly. In order to promote health of the older people,
      geriatricians have to take deep insights for cares as well as medical treatments.
      With such a will, we find the way to prevent diseases in the older people. In
      this review, we describe medical treatments and cares for promoting successful
      aging.

PMID- 15718813
TI  - The role of urtica dioica (urticaceae) in the prevention of oxidative stress
      caused by tourniquet application in rats.
AB  - Tourniquets are used in extremity surgery and provide a relatively bloodless
      field, thereby minimizing blood loss and helping identify the vital structures.
      However, they may cause an ischemia-reperfusion injury with potentially harmful
      local and systemic consequences. Many therapeutic effects such as diuretic,
      natriuretic, hypotensive, anti-rheumatic, anti-prostatic, and in-vitro anti
      oxidant effects of the Urtica dioica (UD) have been determined. In the present
      study, we aimed to investigate the potential role of UD plant for prevention of
      oxidative stress in muscle tissues generated by tourniquet application in rats.
      Wistar rats were used in this study. The UD extract or 1.15% KCl aqueous
      solution, in which UD leaf samples were homogenized, was given to each group of
      eight rats once a day for 5 days through an intraesophageal canule. No treatment
      was applied to untreated group. Tourniquets were applied to the left posterior
      limb of rats for 1 or 2 h followed by a reperfusion period of 1 h. After the
      ischemia and reperfusion, the rats were killed with a high dose of anesthetic
      drug, and malonyldialdehyde (MDA) levels were measured in their tibialis anterior
      muscles. Basal MDA levels were obtained from tibialis anterior muscles of 8
      control rats, which were not exposed to ischemia. MDA levels were lower in the UD
      treated rats than those in untreated and KCl-treated rats after either 1 or 2 h
      of ischemia and 1 h reperfusion. These results indicate that UD has a potential
      antioxidant effect on ischemic muscle tissues.

PMID- 15718814
TI  - Treatment of Staphylococcus epidermidis endophthalmitis with intravitreal
      moxifloxacin in a rabbit model.
AB  - Staphylococcus epidermidis is one of the most common causes of postoperative
      infectious endophthalmitis, which is a serious complication of ocular surgery and
      penetrating trauma. Moxifloxacin is a newly developed fluoroquinolone with a
      potent antimicrobial activity. Corticosteroids are used in endophthalmitis to
      suppress devastating intraocular inflammatory response. This study was designed
      to assess the efficacy of intravitreal moxifloxacin alone and in combination with
      intravitreal dexamethasone. To the best of our knowledge, there is no published
      report demonstrating the effect of intravitreal moxifloxacin on bacterial
      endophthalmitis. One eye of each rabbit (n=24) was infected by inoculation of
      10(5) colony-forming units (CFU) of S. epidermidis into the vitreus cavity.
      Rabbits received intravitreal injection of moxifloxacin (50 microg) or a
      combination of moxifloxacin (50 microg) and dexamethasone (400 microg). No
      treatment was given to control group. Clinical and histopathological examination
      scores and microbiological analysis of vitreus aspirates were compared. In the
      treatment groups, the clinical and histopathological scores and mean CFU were
      significantly lower than those in the control group (p <0.05) but showed no
      significant difference between the treatment groups. These results suggest that
      intravitreal injection of moxifloxacin is effective against S. epidermidis in
      this experimental rabbit model. Moxifloxacin may be a promising agent in the
      treatment of bacterial endophthalmitis.

PMID- 15718815
TI  - Health characteristics of elderly Japanese requiring care at home.
AB  - The number of elderly subjects requiring care is rapidly increasing, however,
      their health status has not been well studied. The purposes of this study were to
      describe the health characteristics of the elderly at home who were using long
      term care insurance, and to clarify factors that influence dependence for
      activities of daily living (ADL). The subjects were 194 elderly people living at
      home, who were approved for care. The items surveyed were the demographic
      characteristics, care level (or level of dependence for ADL), Barthel index, grip
      strength, thigh muscle volume, cognitive impairment using the mini-mental state
      examination (MMSE), depressed mood using the geriatric depression scale (GDS-15),
      and serum albumin and hemoglobin levels. The grip strength (p=0.0001), thigh
      muscle volume (p=0.0030), MMSE score (p=< 0.0001) and serum albumin level (p= <
      0.0001) decreased, while the GDS-15 score (p=0.0142) increased with deteriorating
      care levels. The proportion of subjects not requiring assistance for the items
      "bathing" and "stair-climbing" in the Barthel index was markedly low in the
      subjects belonging to the relatively low (mild) care levels. The logistic
      regression analysis showed that factors associated with dependence for "bathing"
      and "stair-climbing" were the use of day-services, male sex, decline of grip
      strength, and a high GDS-15 score. In conclusion, it is important to strengthen
      the muscles of the upper half of the body, and to correct depressed moods for
      maintaining levels of ADL in the elderly requiring care at home.

PMID- 15718816
TI  - Unfavorable outcome of burn patients with neuropsychiatric disorders.
AB  - To assess the outcome of burn patients with neuropsychiatric disorders, we
      performed a 7-year retrospective review of burn patients admitted to the National
      Defense Medical College. Seventy-seven skin burn patients over 10 years of age
      were included in this study and divided into two groups, neuropsychiatry and
      control groups. The neuropsychiatry group consisted of self-inflicted burn
      patients (n=21) and burn patients with a neurological disorder (n=18), who could
      not move away from burning source due to neurological problems. The control
      subjects (n=38) had been healthy before burn. No significant differences in the
      age, gender or causes of burn were observed between the two groups. Notably,
      total burned surface area, area of full-thickness burn, and mortality are greater
      in the neuropsychiatry group than those in the control. However, after matching
      the patients for the severity of burn injuries, the above parameters show no
      significant differences between the two groups. Therefore, the outcome of the
      burned patients depends on the patients' will and ability to move away from the
      burning source. Whenever we treat severe burn patients, we should assess their
      neuropsychiatric conditions.

PMID- 15718817
TI  - The threshold cadmium level that causes a substantial increase in beta2
      microglobulin in urine of general populations.
AB  - Cadmium (Cd) is a toxic element ubiquitous in the environment, and general
      populations have been exposed to this element primarily via foods. Thus, the
      critical level of non-occupational Cd exposure to cause any health effects among
      general populations is of public health as well as toxicological concern. The
      objectives of the present study were to examine the quantitative relationship
      between cadmium (Cd-U) and beta2-microglobulin in urine (beta2-MG-U) as a marker
      of exposure to Cd and as a marker of renal tubular dysfunction, respectively, and
      to identify a threshold Cd-U, if present, in causing a substantial increase in
      beta2-MG-U. Thus, paired data on geometric mean (GM) Cd-Ucr (i.e., Cd-U as
      corrected for creatinine [cr] concentration) and GM beta2-MG-Ucr (beta2-MG-U as
      corrected for cr) of residents in polluted as well as nonpolluted areas in Japan
      were retrieved in international and domestic sources. In practice, 245 cases of
      the data pairs were obtained in 51 articles published since 1975. Statistical
      analysis on ordinary scales disclosed that beta2-MG-Ucr increased markedly when
      Cd-Ucr exceeded a certain level. The relation between the two parameters after
      double-logarithmic conversion was in a shape of the letter J or a stick for ice
      hockey. Analysis for Cd-Ucr at the flexion point gave Cd-Ucr of 4 (on double
      logarithmic scales) or 7 microg/g cr (on ordinary scales). Cd-Ucr levels that
      correspond to a beta2-MG-Ucr of 1,000 microg/g cr were estimated to be 8-9
      microg/g cr, by ordinary and logarithmic assumption as well as by the 3rd degree
      regression analysis. Thus, it is concluded that there is a threshold Cd-Ucr level
      that leads to a substantial increase in beta2-MG-Ucr, and that the threshold
      level is greater than 4 microg/g cr.

PMID- 15718818
TI  - The effects of continuous ambulatory peritoneal dialysis and hemodialysis on
      serum pepsinogen concentrations in patients with chronic renal failure.
AB  - Pepsinogen, the precursors of pepsin, is classified into two subtypes: pepsinogen
      I (PG I) and pepsinogen II (PG II). Patients with impaired renal function are
      associated with elevated concentrations of serum pepsinogen. Contradictory
      results have been reported about the effect of dialysis on the serum pepsinogen
      levels, as the previous studies were conducted only in a particular period of
      dialysis. We therefore investigated the effect of continuous ambulatory
      peritoneal dialysis (CAPD) or hemodialysis on serum pepsinogen levels in patients
      with chronic renal failure (CRF) before and after dialysis treatment. Thirty-four
      patients with CRF were enrolled in this study and were treated by CAPD (n=22) or
      hemodialysis (n=12). As a control group, subjects with normal renal function were
      included (n=20). Serum PG I and PG II levels were measured in control subjects
      and CRF patients before dialysis treatment and after three-month dialysis
      treatment. Before dialysis treatment, serum PG I levels were significantly higher
      in CRF patients than control subjects. In patients treated by CAPD, the serum PG
      I levels were significantly decreased but its levels were still higher than the
      values of the control subjects, whereas PG I levels remained unchanged in
      patients treated by hemodialysis. There were no differences in serum PG II levels
      between control subjects and CRF patients before or after dialysis treatment.
      Thus, CAPD is more effective than hemodialysis in the clearance of PG I.

PMID- 15718819
TI  - Prognostic factors for the surgical management of peripheral nerve lesions.
AB  - Although the evaluation and treatment of patients with peripheral nerve injuries
      has evolved and improved over the years, there are still some arguments on the
      methods and results of surgery. We reviewed retrospectively the clinical,
      electrophysiological and surgical characteristics of peripheral nerve lesions for
      1,636 nerves in 1,565 patients who had been managed in our department in a 10
      year period. The most common cause of injuries was gunshot wound in 56.3% of all
      patients, followed by sharp lacerations (20.6%), fractures (10.6%) and tractions
      (5.1%). Among 1,636 cases of nerve injuries, the most frequently wounded nerve
      was median nerve (32.3%), followed by ulnar (24.1%), radial (12.1%), sciatic
      (10.7%) and peroneal nerves (7.7%), and brachial plexus (7.7%). Simple
      decompression was the most preferred technique for nerve repair in 27.8%. The
      electrophysiological improvement was observed in 66.8%, as assessed by
      electromyography. Clinical improvement was found in 58.4%, as judged by muscle
      strength grading. If the nerve is compressed or contused, but remains intact, the
      improvement is satisfactory after surgery. The type of injury, its time of
      occurrence, initial deficit, and degree of recovery expected are important issues
      in establishing the treatment plan, which may range from skilled observation to
      extensive surgical intervention.

PMID- 15718820
TI  - Reproductive factors affecting the bone mineral density in postmenopausal women.
AB  - Osteoporosis has been defined as a metabolic bone disease characterized by a loss
      of bone mineral density (BMD) greater than 2.5 standard deviations below young
      adult peak bone mass or the presence of fracture. By considering that some
      factors related to female reproductive system might influence the ultimate risk
      of osteoporosis, we aimed to investigate if a relationship exists between the
      present BMD of postmenopausal women with their past and present reproductive
      characteristics. The present study focused on how BMD could be affected by the
      following factors in postmenopausal women, such as age at menarche, age at first
      pregnancy, the number of pregnancies and total breast-feeding time. We reviewed
      detailed demographic history of 303 postmenopausal women. According to the
      results of the present study, a negative correlation was found between the number
      of parities and BMD. The BMD values decreased as the number of pregnancies
      increased. When the BMD values for lumbar vertebrae 2 and Ward's triangle were
      investigated, it was observed that a significant difference exists between the
      women with no child birth and those with more than five parities. There was a
      significant relationship between age at first pregnancy and BMD values at the
      lumbar vertebrae 2 and Ward's triangle. Women who had five or more abortions were
      found to have significantly lower spine BMD values compared to women who had no
      abortions or women who had one or two abortions. These findings indicate that the
      increased risk of osteoporosis is associated with the increased number of
      pregnancies and abortions and higher age at first pregnancy.

PMID- 15718821
TI  - A hippocampal lesion detected by high-field 3 tesla magnetic resonance imaging in
      a patient with temporal lobe epilepsy.
AB  - Nearly 80% of patients with temporal lobe epilepsy have some types of lesion
      identified by conventional 1.5 tesla (T) magnetic resonance imaging (MRI). We
      performed high-field 3 T MRI in a 5-year-old patient with recurrent complex
      partial seizures who was diagnosed as having right temporal lobe epilepsy based
      on the results of single photon emission computed tomography and ictal video
      electroencephalogram monitoring, because 1.5 T MRI failed to detect any
      abnormalities in the suspected region. High-field 3 T MRI revealed a small high
      intensity lesion on fast spin-echo short inversion time inversion-recovery images
      of the hippocampus, possibly responsible for the seizures. This is the first
      report detecting a hippocampal lesion by 3 T MRI, which could not be found by
      conventional 1.5 T MRI.

PMID- 15718822
TI  - Latent fatality due to hydatid cyst rupture after a severe cough episode.
AB  - Hydatid disease is a parasitic disease caused by Echinococcus granulosus
      characterised by cyst formation in various organs. The infestation mostly
      involves the liver. Hydatid cysts of the liver can rupture either spontaneously
      or due to trauma. Incidence of rupture is about 3-17% of all cases with hydatid
      disease. Unless treated surgically, rupture can result in death. Here, we present
      a case of hydatid cyst ruptured after a severe cough episode and disseminated
      first to the subcapsular area, then to the peritoneal space. Probably due to a
      decrease in parenchymal pressure in the liver after decompressive effect of
      rupture, the patient felt an improvement in abdominal pain, refused operation,
      and left the hospital on his own responsibility. This unfortunate relief resulted
      in a delay of 55 hours in management. The leakage of liquid materials into
      peritoneal space resulted in a severe inflammatory reaction and eventually death
      of the patient. The patient died of a late peritonitis rather than anaphylaxis,
      which is the most common reason for death in such patients. As a conclusion,
      physicians should be aware of a temporary relief in abdominal pain after cyst
      rupture that may cause a delay in management and in turn loss of patient due to
      peritonitis.

PMID- 15718823
TI  - Transscleral permeability of fluorescent-labeled antibiotics.
AB  - PURPOSE: To determine the in vitro transscleral permeability of antibiotics for
      posterior segment infection. METHODS: Scleral sections from moist chamber-stored
      human globes were mounted in a 2-compartment perfusion chamber. Fluorescent
      labeled vancomycin, polymyxin B, or penicillin G was added to the episcleral
      surface, while the choroidal side was slowly perfused with balanced salt solution
      (Alcon Laboratories, Inc., Ft. Worth, TX). The perfusate was collected and
      fluorescence was measured using a fluorometer. From the measurements,
      permeability (Ktrans) was calculated. Photomicrographs were taken with a
      fluorescent microscope to evaluate tissue absorption. RESULTS: The Ktrans values
      (cm/s, mean +/- standard error) were 6.66 +/- 1.46 x 10(-7) for vancomycin, 3.90
      +/- 0.59 x 10(-7) for polymyxin B, and 1.89 +/- 0.21 x 10(-6) for penicillin G.
      The percent of antibiotic that diffused across the sclera from the donor chamber
      in 24 hours was 20.6 +/- 4.2 for vancomycin, 12.6 +/- 2.0% for polymyxin B, and
      50.8 +/- 4.8% for penicillin G. CONCLUSIONS: This study shows that human sclera
      is more permeable to lower molecular weight, water-soluble penicillin G than to
      vancomycin or polymyxin B. The data suggests that a local, noninvasive,
      transscleral drug-delivery method may be reasonable for treating intraocular
      infections.

PMID- 15718824
TI  - Glucocorticoid-induced changes in the global gene expression of lens epithelial
      cells.
AB  - AIMS: Clinically, steroid use is accompanied by a risk for posterior subcapsular
      cataracts (PSCs). PSC possibly involves perturbation of lens epithelial cell
      proliferation and differentiation; however, the underlying mechanism is unknown.
      In this study, we aimed to characterize changes in gene expression in human lens
      epithelial cells exposed to glucocorticoid using DNA microarray hybridization.
      METHODS: Human lens epithelial cells (HLE B-3) were treated with dexamethasone (1
      microM) for 24 or 48 hours or with vehicle (0.01% dimethylsulfoxide) and the
      derived cRNA was hybridized to U133A microarrays. Data were processed using the
      Affymetrix program Micro Array Suite, and ontological analyses were performed
      using the software dChip, filtering to exclude transcripts up- or down-regulated
      by less than 2-fold. RESULTS: At 24 hours, 57 transcripts were upregulated
      relative to controls by greater than 2- fold and 50 were downregulated by greater
      than 2-fold. At 48 hours, 92 transcripts were upregulated and 42 were
      downregulated. Twenty-two upregulated and 2 downregulated transcripts were shared
      between the 24-hour and 48-hour data sets. The predominant ontological groupings
      were: signal transduction, transcription factor activity,
      cytoskeleton/ECM/adhesion, transport, and cell cycle/development. Alternate
      ontological interpretations are possible. CONCLUSIONS: The data indicate steroid
      treatment of lens epithelial cells is associated with significant changes in gene
      expression in several functional categories and these include transcripts related
      to cell proliferation.

PMID- 15718825
TI  - Effects of antioxidant treatment on normal and diabetic rat retinal enzyme
      activities.
AB  - Diabetes mellitus is characterized by hyperglycemia and, in chronic disease, by
      microvascular pathologies, especially in the kidney, peripheral nerve, and eye.
      Although hyperglycemia can be controlled with insulin and/or antihyperglycemic
      medications, diabetic retinopathy continues to be the leading cause of blindness
      in the United States. Because increased oxidative stress may be a cause of
      retinopathy, this study examined the hypothesis that administration of exogenous
      antioxidants can restore a more balanced oxidative condition. Normal and 30-day
      streptozotocin-induced diabetic Sprague-Dawley rats received daily
      intraperitoneal doses (10 mg/kg) of beta-carotene, alpha-lipoic, and Pycnogenol
      individually or in combinations for 14 days, after which retinae were dissected
      and fractionated for the assay of activities of glutathione reductase,
      glutathione peroxidase, gamma-glutamyl transferase, and superoxide dismutase. In
      normal rats, treatment with antioxidant combinations led to a decrease in gamma
      glutamyl transferase activity; beta-carotene plus pycnogenol treatment decreased
      the activity of both glutathione-related enzymes. Decreased retinal gamma
      glutamyl transferase activity of diabetic rats was normalized by the
      administration of pycnogenol alone or in combination with beta-carotene. In
      diabetic rats, retinal glutathione reductase activity increased after treatment
      with beta-carotene alone or with pycnogenol. Treatment with pycnogenol and alpha
      lipoic acid alone or in combination decreased the activity of glutathione
      peroxidase, while this activity was increased after treatment with a combination
      of all antioxidants. Elevated activity of superoxide dismutase in diabetic retina
      was normalized by treatment with alpha-lipoic acid and with pycnogenol and beta
      carotene in combination, but not with all three together. Antioxidants can access
      the retina and, once there, can alter antioxidant enzyme activities. In both
      normal and diabetic rats, combinations of antioxidants have different effects on
      retinal antioxidant enzyme activities than do individual antioxidants.

PMID- 15718826
TI  - Comparison of ophthalmic gatifloxacin 0.3% and ciprofloxacin 0.3% in healing of
      corneal ulcers associated with Pseudomonas aeruginosa-induced ulcerative
      keratitis in rabbits.
AB  - OBJECTIVE: Evaluation of gatifloxacin 0.3% ophthalmic solution efficacy in a
      corneal ulcer model of Pseudomonas keratitis. METHODS: Heptanol-induced corneal
      ulcers in New Zealand White rabbits (n = 41; 8 females/group) were inoculated
      with 10(6) CFU of Pseudomonas aeruginosa. Gatifloxacin 0.3% dosing varied among 4
      groups with frequencies of 16-48 doses/day (days 1-2), 3-16 doses/day (days 3-7),
      and maintenance dosing of 3-4 doses/day (days 8-22). Ciprofloxacin 0.3% was
      administered as labeled for corneal ulcers, with 44 doses on day 1, 16 doses on
      day 2, and 4 doses/day on days 3-21. RESULTS: All eyes showed evidence of
      infection by 48 hours postinoculation with 36 of 41 eyes (87.8%) exhibiting
      moderate-to-severe keratitis. All eyes exhibited corneal healing by day 15, with
      no significant differences among groups. Three of 4 groups receiving gatifloxacin
      tended to have smaller fluorescein retention area scores than did the
      ciprofloxacin group. No eyes tested positive for Pseudomonas at the end of the
      study. No corneal precipitates were found following as many as 48 doses/day of
      gatifloxacin. CONCLUSION: Ophthalmic gatifloxacin 0.3% is at least as effective
      as ciprofloxacin at healing corneal ulcers infected with Pseudomonas aeruginosa
      when gatifloxacin is administered less frequently than ciprofloxacin. Trends
      favored gatifloxacin in fluorescein retention scores.

PMID- 15718827
TI  - Effects of retinoic acid on retinal pigment epithelium from excised membranes
      from proliferative vitreoretinopathy.
AB  - It has been reported that retinoic acid (RA) may inhibit the growth of RPE and be
      used in the treatment of proliferative vitreoretinopathy (PVR). However, previous
      reports in this field have been conflicting. The main reason for these
      contradictory findings is that different methods for evaluating the effects of RA
      on RPE from different species have been used. In human specimens, only RPE from
      the donor eye (stationary) but not RPE from the PVR membrane (already at active
      proliferation status) have been tested. This study tested the effects of RA on
      the growth of RPE using a novel in vitro model: RPE from the PVR membranes, which
      simulates the in vivo situation of PVR patients better than RPE from the donor
      eyes. This study also used various methods to solve the conflicting results
      reported previously. We found that both all transretinoic acid (all-RA) and 13
      cis-retinoic acid (cis-RA) can promptly (though not completely) inhibit
      proliferation of RPE (inhibition rate of 89%-90%) over a very wide range of
      concentrations (10(-9)-10(-5) M) and various lengths of periods (2-12 days) in a
      dose-dependent and time-dependent manner and without evident cytotoxic effects.
      Previously reported disadvantages discovered from the study of RPE from donor
      eyes, e.g., the absence of inhibitory effects on the early passages of cultured
      cells and inhibition occurring only after long-term treatment, do not present in
      RPE cells from the PVR membrane. The proliferation of RPE recovered from the
      inhibition by RA rapidly after the discontinuation of treatment, indicating that
      a continuous supply of the drug over a long period, i.e., until the breakdown of
      the blood-retinal barrier has been repaired, is essential for the success of drug
      treatment of PVR.

PMID- 15718828
TI  - Clinical evaluation of the intraocular pressure in patients with glaucoma or
      ocular hypertension by a self-assessable tonometer.
AB  - PURPOSE: To investigate the clinical efficacy of a new patient-operated
      intraocular pressure tool, the Proview eye pressure monitor (PEPM; Bausch & Lomb,
      Inc., Rochester, NY), for monitoring intraocular pressure (IOP) in patients with
      glaucoma or ocular hypertension. PATIENTS AND METHODS: One hundred and forty eyes
      of 70 Taiwanese patients from the Tri-Service General Hospital (Taiwan, Republic
      of China) who had been diagnosed with ocular hypertension or glaucoma were
      studied. After being fully trained during an initial clinic visit, patients
      measured their own IOP with the PEPM at home. The IOPs were measured again using
      a Haag-StreitBern Goldmann tonometer (GT; Haag-Streit, Koniz, Switzerland) during
      subsequent outpatient visits. The training time, assessment of the patients' ease
      of PEPM use, and accuracy of measured PEPM IOPs in relation to GT IOPs were
      recorded and analyzed. RESULTS: Relative to GT readings, PEPM readings tended to
      be overestimated at lower pressure (<10 mmHg) and underestimated at higher
      pressure (>20 mmHg). Between 10 to 20 mmHg, PEPM measurements did not
      significantly differ from GT measurements. Up to 80% of the PEPM measurements
      fell within +/- 3 mmHg of the corresponding GT readings. When consideration was
      limited to GT readings of > or =21 mmHg, PEPM measured IOPs of > or =21 mmHg with
      a sensitivity of 80% and a specificity of 90%. The mean satisfaction rating of
      PEPM use was 88.3 +/- 2.0 (maximum, 100). The mean training time for appropriate
      use of PEPM was 17.9 +/- 4.0 minutes. The older the patients, the longer the
      training time that was required. CONCLUSION: Our data suggest that after
      appropriate training: (1) PEPM and GT measurements correspond well between 10
      mmHg and 20 mmHg and (2) PEPM could offer patients with glaucoma or ocular
      hypertension an easy-to-use, substantially reliable means of selfmonitoring IOP.

PMID- 15718829
TI  - Intravitreal tissue plasminogen activator and pneumatic displacement of
      submacular hemorrhage secondary to retinal artery macroaneurysm.
AB  - PURPOSE: To assess the efficacy of treating submacular hemorrhages secondary to
      retinal arterial macroaneurysm with intravitreous tissue plasminogen activator
      (tPA) and gas. PATIENTS AND METHODS: Six consecutive patients (6 eyes) with
      submacular hemorrhage secondary to retinal arterial macroaneurysm were included
      in this study. Tissue plasminogen activator, at a dose of 50 microg/0.1 mL, was
      injected through the pars plana into the vitreous cavity. Gas (0.3-0.5 mL of
      perfluoropropane) instillation followed tPA injection, either immediately after
      injection or sometime during the next day. RESULTS: Best postoperative visual
      acuity improved in 5 of 6 eyes (83%) and was unchanged in 1 of 6 (17%) eyes. In 5
      of 6 (83%) eyes, the procedure resulted in complete or partial displacement of
      submacular hemorrhage out of the foveal area. CONCLUSIONS: Intravitreous
      injection of tPA and gas, followed by prone positioning of the patient, is an
      effective and simple treatment of submacular hemorrhage secondary to retinal
      arterial macroaneurysm. No complication occurred in this series.

PMID- 15718830
TI  - Comparison of the efficacy and safety of dorzolamide 2% when added to brimonidine
      0.2% or timolol maleate 0.5% in patients with primary open-angle glaucoma.
AB  - OBJECTIVE: To determine the ocular hypotensive efficacy and safety of dorzolamide
      when added to brimonidine or timolol in patients with uncontrolled primary open
      angle glaucoma (POAG). PATIENTS AND METHODS: This is a 1-year prospective open
      label clinical trial of 48 consecutive POAG patients with inadequate intraocular
      pressure (IOP) control while using brimonidine 0.2% (23 patients) and timolol
      0.5% (25 patients), 2 times daily. Patients were assigned to receive dorzolamide
      2% as adjunctive therapy, added 3 times daily to brimonidine or timolol. IOP was
      measured on week 2, and months 3, 6, 9, and 12. RESULTS: A significant reduction
      in IOP from the baseline was observed after dorzolamide use in both groups at
      visits during that year (P < 0.001). Overall, mean IOP reduction was 5.6 +/- 1.9
      mmHg with the brimonidine-dorzolamide combination, and 6.8 +/- 1.7 mmHg with
      timolol-dorzolamide after 1 year of treatment; the difference was significant (P
      = 0.029). No statistical differences existed between the groups for adverse
      events (P < 0.05). CONCLUSION: The addition of dorzolamide to brimonidine or
      timolol has significant IOP-lowering efficacy during 1 year in patients with POAG
      whose IOPs were inadequately controlled with brimonidine or timolol alone. The
      IOP-lowering effect of the timolol-dorzolamide combination at 1 year was more
      pronounced than brimonidine-dorzolamide. Both combinations were well-tolerated by
      the patients.

PMID- 15718831
TI  - Efficacy of latanoprost in patients with chronic angle-closure glaucoma and no
      visible ciliary-body face: a preliminary study.
AB  - The aim of this study was to evaluate the efficacy of 0.005% latanoprost in
      lowering intraocular pressure (IOP) in patients with chronic angle-closure
      glaucoma (CACG) and no visible ciliary-body face. Fourteen eyes of 14 Korean
      patients with CACG with 360 degrees of peripheral anterior synechiae (PAS) and an
      IOP greater than 21 mmHg without medication were treated with 0.005% latanoprost
      once-daily. All patients completed 3 months of treatment with latanoprost. The
      IOP, which was 30.3 +/- 4.5 (mean +/- standard deviation) mmHg at baseline,
      decreased to 22.6 +/- 4.9 mmHg after 1 week, 19.6 +/- 5.5 mmHg after 1 month,
      19.4 +/- 4.9 mmHg after 2 months, and 21.5 +/- 5.9 mmHg after 3 months of
      treatment with latanoprost (P < 0.01 for each). Ultrasound biomicroscopy of the
      anterior chamber angle showed anterior bowing of the iris with total occlusion of
      the angle by PAS, except for 5 eyes with focal microscopic openings to the
      ciliary-body face at various angles. Adverse ocular events were well-tolerated
      and transient. In this preliminary study, treatment with 0.005% latanoprost once
      daily resulted in a significant reduction in IOP in CACG patients with 360
      degrees of PAS on gonioscopy. Our results suggest that latanoprost may be
      considered as a therapy of choice in these rare cases.

PMID- 15718832
TI  - Ocular toxicity of intravitreal indocyanine green.
AB  - We report 6 cases of indocyanine green (ICG)-related ocular toxicity after
      intravitreal ICG usage. Five cases had preoperative diagnosis of macular hole, 1
      case had preoperative rhegmatogenous retinal detachment complicated with
      proliferative vitreoretinopathy. All cases received vitrectomy, ICG-assisted
      internal limiting membrane (ILM) peeling and air-fluid exchange. All eyes had
      residual ICG left at the end of surgery. Patients were followed up with indirect
      ophthalmoscopy, visual acuity, color fundus photography, fluorescein angiography,
      and ocular coherence tomography. Circular foveal retinal pigment epithelium
      atrophy larger than the area of macular hole and surrounding cuff was noted in 4
      of 5 cases with preoperative macular hole. The other eye with preoperative
      diagnosis of macular hole had shallow anterior chamber and low intraocular
      pressure lasting for 1 week postoperatively. Diffuse retinal pigment epithelial
      atrophy was noted in the eye with preoperative proliferative vitreoretinopathy.
      Four eyes demonstrated optic atrophy postoperatively. Ocular toxicity caused by
      ICG may present as pigment epithelial atrophy, which is characteristically larger
      than the previous area of macular hole and surrounding cuff. Disc atrophy,
      retinal toxicity, and ocular hypotony were also observed in some cases. To
      prevent toxicity, residual ICG and ICG-stained ILM must be removed as completely
      as possible.

PMID- 15718833
TI  - Care of patients with chronic hepatitis B and HIV co-infection: recommendations
      from an HIV-HBV International Panel.

PMID- 15718834
TI  - CD8 T-cell responses in early HIV-1 infection are skewed towards high entropy
      peptides.
AB  - OBJECTIVE: To understand the mechanisms underlying the differential targeting of
      T-cell responses during HIV-1 disease progression. DESIGN: We performed a cross
      sectional analysis of HIV specific CD8 T-cell responses in peripheral blood
      mononuclear cells (PBMC) obtained from 21 subjects with well characterized acute
      or early infection and 88 subjects with chronic HIV-1 infection. We also
      performed a longitudinal analysis of T-cell responses in five early infected
      subjects one of whom was studied extensively over a 4-year-period. METHODS: PBMC
      were stimulated with pools of peptides encompassing all of the HIV-1 proteins in
      an interferon-gamma ELISpot assay. A mean entropy score was calculated for each
      peptide in the HIV-1 genome. RESULTS: The early infected group preferentially
      targeted variable peptides with higher entropy while responses towards more
      conserved peptides with lower entropy predominated in the group with chronic
      infection. In five early infected subjects followed longitudinally, responses to
      variable proteins declined while those to conserved proteins increased over time.
      In the subject who was followed for 4 years, epitopes in Vif and Nef were
      targeted early and escape occurred in three of these four epitopes. During the
      chronic phase of his infection, the early responses waned with an associated
      increase in breadth of T-cell responses mainly to Gag and Pol epitopes.
      CONCLUSION: Taken together, these data demonstrate that HIV-specific CD8 T cells
      are directed preferentially to the variable peptides in early infection but
      diminish in frequency during chronic disease, in large part due to cytotoxic T
      lymphocyte escape.

PMID- 15718835
TI  - Comparison of HIV-specific CD8 T-cell responses among uninfected individuals
      exposed to HIV parenterally and mucosally.
AB  - OBJECTIVE: To assess the influence of route of HIV exposure on the development of
      HIV-specific CD8 T-cell responses in exposed, uninfected (EU) individuals.
      DESIGN: Two groups of EU exposed to virus through either sexual or intravenous
      contact were studied. Group I included subjects (n = 20) who had unprotected
      sexual contact with known HIV-infected partners and no intravenous HIV exposure;
      Group II included individuals (n = 27) who had shared needles with HIV-infected
      partners and had no sexual exposure to this virus. Between-group comparisons were
      made for the proportion of responders, breadth, magnitude, and specificity of HIV
      specific responses. METHODS: : The interferon-gamma ELISPOT assay was used to
      detect HIV-specific effector activity. Peripheral blood mononuclear cells (PBMC)
      from each subject were stimulated with a panel of HIV peptides restricted to the
      MHC class I alleles expressed by the individual. RESULTS: A similar proportion of
      EU tested from each group (35.0% Group I versus 22.2% Group II) recognized at
      least one HIV peptide. Group I and II subjects recognized HIV peptides with a
      similar cumulative intensity of 130 +/- 67.5 and 182.9 +/- 184.2 spot forming
      cells/1 x 10 PBMC, respectively, and similar magnitude per stimulatory peptide of
      82.7 and 78.4 SFC/1 x 10 PBMC, respectively. The proportion of stimulatory
      peptides derived from HIV Gag, reverse transcriptase, Env, and Nef was not
      significantly different between the two EU groups. HLA-A*0201 restricted HIV
      epitopes immunodominant in infected individuals are rarely stimulatory in EU
      subjects. CONCLUSIONS: Both mucosal and parenteral exposure to HIV can elicit HIV
      specific CD8 T-cell responses with similar characteristics.

PMID- 15718836
TI  - Different subsets of peripheral blood dendritic cells show distinct phenotypic
      and functional abnormalities in HIV-1 infection.
AB  - OBJECTIVES: To analyse the distribution, expression of chemokine receptors and ex
      vivo production of inflammatory cytokines by peripheral blood (PB) monocytes and
      DC in HIV-1+ individuals. DESIGN: Dendritic cells (DC) play an important role in
      the establishment and dissemination of HIV infection. DC interaction with HIV
      depends on expression of HIV receptors and co-receptors. Accumulating evidence
      supports the notion that DC functionality is impaired in HIV-1+ patients.
      METHODS: PB samples from 30 naive-treated HIV-1+ progressors were studied.
      Additionally, 10 adult healthy volunteers (AHV), seven Hepatitis C virus positive
      (HCV+)/HIV-1- patients and five long-term non-progressor HIV-1+ patients (HIV
      1+LTNP) were included as controls. Flow cytometry immunophenotyping was used for
      the identification, enumeration and characterization of monocytes and DC.
      RESULTS: PB myeloid DC (mDC) and plasmacytoid DC (pDC) were significantly
      decreased in HIV-1+ progressors, while unaltered in HIV-1+LTNP. The expression of
      CXCR2 and CXCR4 and of CXCR4 and CCR5 were severely altered on PB mDC and pDC
      from HIV-1+ progressors, respectively. By contrast, both the expression of the
      chemokine receptors analysed and the numbers of CD16+ DC in HIV-1+ progressors
      were not different from AHV, while altered in HCV+/HIV-1- and HIV-1+LTNP.
      Furthermore, PB monocytes and DC from HIV-1+ progressors spontaneously produced
      inflammatory cytokines, in contrast with AHV. CONCLUSIONS: These results support
      the existence of a selective interaction between HIV-1 and both mDC and pDC,
      associated with HCV co-infection-independent spontaneous production of
      inflammatory cytokines, reflecting the occurrence of in vivo activation of the
      immune system, which might further contribute to the impaired DC functionality.

PMID- 15718837
TI  - Cytomegalovirus genotypes present in cerebrospinal fluid of HIV-infected
      patients.
AB  - OBJECTIVE: To compare cytomegalovirus (CMV) strains found in cerebrospinal fluid
      (CSF) of patients with HIV infection and CMV encephalitis with those present in
      the general population with respect to genetic variation in the N terminus of the
      glycoprotein B (gBn)-gene. DESIGN AND METHODS: We sequenced gBn, which is a major
      target of the antiviral immune response, of CMV strains present in CSF of nine
      HIV-infected patients with acute encephalitis, in serum of 18 immunocompetent
      patients with primary CMV infection, and in serum of nine HIV-infected patients
      without neurological illness. Sequences were compared to prototype strains and
      analysed by use of phylogeny. RESULTS: Fourty-four percent (4/9) of gBn-sequences
      present in CSF did not cluster with any of the four gBn-prototype strains.
      Phylogenetic analysis revealed that these sequences represented two further,
      distinct genotypes and comparison of sequences was highly suggestive for
      intragenic recombination. In immunocompetent patients and HIV-infected patients
      without neurological illness, genotype gBn1 was the predominant strain (4/9, 44%
      and 8/18, 42%, respectively). Genotypes distinct from prototype strains were
      found in none of the immunocompetent patients and 22% (2/9) of HIV- infected
      patients without neurological illness. CONCLUSIONS: CMV strains present in CSF of
      HIV-infected patients with encephalitis differ significantly from those present
      in the general population. Intragenic recombination of CMV may be common in
      patients with advanced HIV infection and a source of new CMV strains with altered
      biological properties.

PMID- 15718838
TI  - Immunological and virological efficacy of a therapeutic immunization combined
      with interleukin-2 in chronically HIV-1 infected patients.
AB  - OBJECTIVE: Several lines of evidence suggest that the immune system may control
      HIV-1 replication, but that it could fail in the long term. Strategies aimed to
      elicit specific immune responses may enable patients to contain virus
      replication. METHODS: HIV-1-infected patients were randomized to continue either
      their antiviral therapy alone (controls; n = 37) or with four boosts of
      vaccination combining ALVAC-HIV (vCP1433) and Lipo-6T vaccines (weeks 0, 4, 8,
      12) followed by three cycles of subcutaneous interleukin-2 (weeks 16, 24, 32)
      (Vac-IL-2 group; n = 34). RESULTS: Of the Vac-IL-2 group, 15/32 (47%) exhibited a
      stable HIV p24 antigen-proliferative response compared with 8/33 (24%) controls
      (P = 0.049). After vaccination, 19/33 (58%) of the Vac-IL-2 group exhibited a
      multiepitopic HIV-1-specific CD4 cell proliferative response compared with 9/36
      (25%) of controls (P = 0.006). The breadth and the magnitude of HIV-specific
      interferon-gamma-producing CD8 T cells improved in the Vac-IL-2 group. After
      stopping antiviral drugs, 24% of the Vac-IL-2 group lowered their viral set point
      compared with 5% of controls (P = 0.027). Logistic-regression analysis
      demonstrated that vaccine-elicited immunological responses were predictive of
      virological control (P = 0.046 and 0.014 for stable and multiepitopic CD4 T cell
      responses, respectively). CONCLUSION: This study provides proof of the concept
      that therapeutic immunization before antiviral drug cessation may contribute to
      the containment of HIV replication.

PMID- 15718839
TI  - CD4 cell-monitored treatment interruption in patients with a CD4 cell count > 500
      x 106 cells/l.
AB  - BACKGROUND: Little is known about CD4 cell count changes in patients with high
      CD4 cell counts who interrupt antiretroviral therapy, especially in those with a
      nadir of 250-350 x 10 cells/l. METHODS: Data derived from 139 patients from seven
      prospective cohorts who had > 12 months highly active antiretroviral therapy
      (HAART), CD4 cell count nadir of > 250 x 10 cells/l and at pre-interruption of >
      500 x 10 cells/l. Endpoint was time to CD4 cell count < 350 x 10 cells/l or
      reinitiation of treatment. RESULTS: At interruption, the median CD4 cell count
      was 800 x 10 cells/l, median viral load was 1.7 log10 copies/ml. At the time of
      analysis, 63 (45.3%) had resumed therapy or experienced < 350 x 10 cells/l CD4
      cells over a median interruption of 75 weeks. Of these, 33 (52.4%) experienced a
      decline to < 350 x 10 cells/l and 30 (47.6%) restarted therapy before their CD4
      cell count had fallen below this level. In 43 patients with CD4 cell nadir of 251
      350 x 10 cells/l, median time to therapy resumption or CD4 cell count < 350 x 10
      cells/l was 61 weeks. Higher CD4 cell count nadir, longer duration of viral load
      suppression on therapy, and higher viral load level at interruption were
      independently associated with longer time to restart therapy. The risk of
      clinical events was 5 per 1000 person-years of follow-up. CONCLUSIONS: Patients
      who started therapy with CD4 cell count of 250-350 x 10 cells/l and who later
      interrupted therapy appear able to remain off therapy with a CD4 cell count > 350
      x 10 cells/l for a substantial period of time.

PMID- 15718840
TI  - A randomized, prospective study of phenotype susceptibility testing versus
      standard of care to manage antiretroviral therapy: CCTG 575.
AB  - OBJECTIVE: To assess phenotype susceptibility testing (PHENO) with standard of
      care (SOC) to improve antiretroviral therapy. DESIGN: A prospective, multicenter
      study of 238 patients taking a stable antiretroviral regimen for > 6 months, with
      one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml. METHOD:
      Patients were randomized to receive or not receive PHENO results for selecting
      antiretroviral regimens. Primary outcome was HIV RNA measures. RESULTS: At
      baseline, median CD4 cell count was 277 x 10 cells/l and HIV RNA was 10 000
      copies/ml; 76% had not taken a non-nucleoside reverse transcriptase inhibitor
      drug (NNRTI). There were significant differences between the groups in selection
      of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6,
      reduction in HIV RNA was 0.71 and 0.69 log10 copies/ml for PHENO and SOC,
      respectively; the proportion with < 400 copies/ml (48%) was the same for both
      groups. No differences were seen at month 12. In a subgroup with resistance to
      four or more PI, 50% of the PHENO versus 17% of the SOC had HIV RNA < 400
      copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the
      regimen that were active by phenotype at baseline was a strong independent
      predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity
      cut-offs improved their predictive value. CONCLUSIONS: Although virological
      outcome was similar in both groups, the potential benefit of PHENO was seen in
      patients with more resistant virus. Lack of appropriate cut-offs may have
      partially accounted for the lack of benefit from PHENO and demonstrated the need
      to identify clinically relevant sensitivity cut-off points.

PMID- 15718841
TI  - Frequency of HIV-1 dual subtype infections, including intersubtype
      superinfections, among injection drug users in Bangkok, Thailand.
AB  - OBJECTIVES: To estimate the frequency and incidence of dual HIV-1 subtype
      infections, including superinfections, among recent seroconvertors from a cohort
      of injection drug users (IDUs). METHODS: A total of 1209 HIV-negative IDUs were
      followed in a prospective cohort study at 15 methadone clinics in Bangkok,
      Thailand. After 2308 person-years (PY) of follow-up, 133 seroconverted to HIV-1,
      of which approximately 20% were subtype B and 80% were CRF01_AE (formerly called
      subtype E). Specimens from 126 individuals were available at time of first
      seropositive test and specimens from 80 of these 126 individuals were also
      available more than 12 months later. For each infected participant, we calculated
      the amount of time to superinfection, loss to follow-up, or to the closest visit
      more than 12 months after the time of initial seropositivity. RESULTS: Of all 126
      seroconverters seen at the time of the first seropositive test result, there was
      no apparent case of concurrent dual subtype infection detected despite 2301 PY of
      observation. Overall, the incidence of superinfection was 2.2 per 100 PY [95%
      confidence interval (CI), 0.3-7.8]. The 1-year incidence of CRF01_AE
      superinfection following subtype B primary infection was 3.9 per 100 PY (95% CI,
      0.1-21.9) and the incidence of subtype B superinfection following CRF01_AE
      primary infection was 1.5 per 100 PY (95% CI, 0.04-8.3). CONCLUSIONS:
      Determination of the frequency and incidence of dual HIV-1 subtype infection
      demonstrates that HIV-1 superinfection is not uncommon in a population with high
      HIV-1 incidence with more than one circulating strain.

PMID- 15718843
TI  - Risk of AIDS and death at given HIV-RNA and CD4 cell count, in relation to
      specific antiretroviral drugs in the regimen.
AB  - BACKGROUND: It is unknown whether the relationship between the HIV-RNA/CD4 cell
      count and risk of clinical disease continues to hold true for newer
      antiretroviral drugs approved without data from clinical endpoint trials.
      OBJECTIVE: : To determine and compare whether rate ratios of AIDS and death at
      given, latest HIV-RNA and CD4 cell counts levels were similar, regardless of
      which nucleoside pair and specific third drugs patients received as
      antiretroviral therapy. DESIGN: EuroSIDA observational cohort. A total of 9802
      prospectively followed patients. METHODS: Analysis included patients taking
      combination antiretroviral therapy (CART) regimens containing two non-abacavir
      nucleosides plus a 'third drug' of a non-nucleoside reverse transcriptase
      inhibitor, a (possibly ritonavir boosted) protease inhibitor or abacavir.
      RESULTS: A total of 6814 patients contributed a total of 22 766.6 person-years of
      follow up. Median latest CD4 cell count was 353 x 10 cells/l, HIV-RNA 199
      copies/ml. A total of 900 events of new AIDS or death were observed. AIDS/death
      rates for any given CD4 or HIV-RNA category were similar regardless of specific
      drugs being used. Adjusted rate ratios (RR) for individual drugs compared with
      indinavir (for which clinical endpoint trials are available) were all close to 1
      and with relatively narrow 95% confidence intervals (CI); for example, nelfinavir
      RR, 0.99 (95% CI, 0.76-1.28); efavirenz RR, 0.83 (95% CI, 0.57-1.20); abacavir
      RR, 1.01 (95% CI, 0.64-1.60). Results were similar for different nucleoside
      pairs. CONCLUSIONS: The results indicate that AIDS/death rates for given CD4 cell
      count and HIV-RNA categories are similar, regardless of CART regimen being taken
      and provide reassurance that HIV-RNA and CD4 cell counts in individual patients
      receiving newer drugs have the same meaning, in terms of AIDS/death risk,
      regardless of specific antiretroviral regimen.

PMID- 15718842
TI  - Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent
      peripartum HIV transmission.
AB  - OBJECTIVES: In Africa, single-dose nevirapine (NVPsd), short regimens of
      zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum
      mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy
      of two more PMTCT drug combinations. DESIGN: An open-label intervention cohort in
      Abidjan. METHODS: In 2001-2002, consenting women started oral ZDV 300 mg twice
      daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd
      orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =32
      weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV
      + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg
      per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman
      was assisted to either use breast milk substitutes or breastfeed exclusively.
      Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks,
      confirmed at 6 weeks. The reference group was a cohort receiving a short regimen
      of ZDV > or = 36-38 weeks in 1995-2000 in the same population. RESULTS: A total
      of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV +
      NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis;
      79 children were HIV-infected peripartum. Six-week transmission probability was
      6.5% [95% confidence interval (CI), 3.9-9.1%) with ZDV + NVPsd, a 72% reduction
      compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on maternal CD4,
      clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC
      + NVPsd (P = 0.34 compared with ZDV + NVPsd). CONCLUSIONS: A short-course of ZDV
      + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could
      be added to international guidelines.

PMID- 15718844
TI  - Changes over time in post-seroconversion CD4 cell counts in the Italian HIV
      Seroconversion Study: 1985-2002.
AB  - OBJECTIVE: To determine whether there has been a tendency for early post
      seroconversion CD4 cell counts to change over calendar time. DESIGN: A
      prospective cohort study of individuals with well-estimated dates of
      seroconversion. METHODS: We studied 1251 individuals who seroconverted to HIV in
      Italy between 1985 and 2002, and for whom the first CD4 count was measured within
      2 years of seroconversion and before any use of antiretrovirals. Linear
      regression models were used to assess evidence for a trend in post-seroconversion
      CD4 cell count over time. RESULTS: The median post-seroconversion CD4 cell count
      was 674 x 10 cells/l in those seroconverting between 1985 and 1990, 588 x 10
      cells/l for 1991 to 1994, 559 x 10 cells/l for 1995 to 1998 and 494 x 10 cells/l
      for 1999 to 2002. The post-seroconversion CD4 cell count decreased by an average
      of 8.4 x 10 cells/l per year (95% confidence interval, 4.0-12.9; P < 0.001),
      after adjustment for potential confounders, including interval between HIV
      negative and HIV-positive tests, lag time for first CD4 cell count measurement,
      age at seroconversion, gender, HIV-transmission group, and clinical centre. The
      finding was consistent in sensitivity analyses restricted to those with
      information on acute infection. CONCLUSION: These data suggest a possible
      decreasing trend in CD4 cell count immediately following seroconversion in Italy
      which requires further investigation.

PMID- 15718845
TI  - Questa e quella per me pari sono.

PMID- 15718846
TI  - The efavirenz-induced increase in HDL-cholesterol is influenced by the multidrug
      resistance gene 1 C3435T polymorphism.
AB  - Efavirenz treatment has been associated with increases in HDL-cholesterol
      concentrations, and the circulating levels of the drug have been related to the
      multidrug resistance gene 1 (MDR-1) C3435T polymorphism. The changes in the
      measured lipid parameters were evaluated in 59 HIV-infected patients initiating
      efavirenz-based treatment at baseline and at 12 months of follow-up. Efavirenz
      treatment increased HDL-cholesterol. The changes in concentrations appeared to be
      influenced by the MDR-1 gene polymorphism, in which CC > CT > TT.

PMID- 15718847
TI  - Reversal of HIV-1-associated osteoporosis with once-weekly alendronate.
AB  - HIV-1-infected patients with osteoporosis were randomly assigned to alendronate
      70 mg once-weekly plus dietary counselling (n = 11) or diet counselling alone (n
      = 14). At week 96, 27% of patients on alendronate versus 96% of controls
      presented with osteoporosis. Spine bone mineral density (BMD) increases were
      detected at week 48, and progressed thereafter. Improvements in trochanter BMD
      were obtained after 2 years. Once-weekly oral alendronate may be an effective and
      safe treatment for HIV-1-associated osteoporosis.

PMID- 15718848
TI  - Safety of long-term interruption of successful antiretroviral therapy: the ATHENA
      cohort study.
AB  - We studied the dynamics of CD4 cell counts after the interruption of
      virologically successful highly active antiretroviral therapy (HAART) in 139
      patients. Changes in CD4 cell counts during HAART interruption followed a
      biphasic pattern: an initial rapid decline during the first month followed by a
      slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just
      above the mean pre-HAART level. This limits the feasibility of structured
      treatment interruptions for patients with low nadir CD4 cell counts.

PMID- 15718850
TI  - Conjunctival intraepithelial neoplasia in association with HIV infection.

PMID- 15718849
TI  - Potential for medical transmission of HIV in Ethiopia.
AB  - The potential medical transmission of HIV through unsafe medical injections was
      evaluated in 16 rural health institutions in Ethiopia. Most institutions reported
      re-using disposable needle/syringes, and 12% of observed injections were given
      with used, disposable syringes prepared for re-use. Analysis of used needle
      flushes showed no HIV RNA; however, the sensitivity of our method was limited.
      Despite the re-use of disposable needles, medical injection practices are not
      likely to contribute significantly to HIV transmission in this region.

PMID- 15718851
TI  - Increasing prevalence of male homosexual partnerships and practices in Britain
      1990-2000: but why?

PMID- 15718858
TI  - Endoscopic treatment of reflux: a quest for the holy grail of reflux?

PMID- 15718859
TI  - Information assimilation and distribution challenges and goals for real and
      virtual journals.
AB  - The distribution of biomedical information was transfigured over three centuries
      ago with the introduction of scientific journals. This enabled the widespread
      dissemination of data to global audiences and greatly facilitated not only the
      advance of science but amplified the interaction between investigators despite
      their different locations. This process continued to expand in a linear fashion
      prior to the emergence of the Internet. The latter system has prompted a
      phenomenal augmentation of information accessibility, and its ever-expanding use
      has resulted in an exponential increase in the demand for digital technology and
      online resources. This technology has achieved unprecedented acceptance in the
      scientific domain and enabled publishers to expeditiously produce and distribute
      journal contents online. Such unparalleled access to information has sparked
      incendiary debate within the scientific community and among journal publishers in
      regard to numerous issues. It is thus much debated as to who has the right to
      "own" or control intellectual property, whether information should be made freely
      available to the online global community, how to gauge the legitimacy and
      authenticity of published research, and the need to reexamine the feasibility and
      profitability of paper journals in consideration of the digital, online formats
      that continue to gain popularity. To assess the current status of the situation,
      a meeting of journal editors, research scientists, and publishing executives was
      held in Constance, Germany, on June 26, 2004, to discuss these issues and
      formulate strategies and recommendations for the future of biomedical publishing.
      Herewith we provide a summation (manifesto) of the meeting's proceedings and
      provide a consensus opinion with the aim of illuminating the subject and also
      proposing some putative solutions for the major challenges that currently
      confront the scientific and publishing community.

PMID- 15718860
TI  - Present status of photodynamic therapy for high-grade dysplasia in Barrett's
      esophagus.
AB  - GOALS: Review recent developments in Barrett's dysplasia including regulatory
      approval of porfimer sodium photodynamic therapy. BACKGROUND: Barrett's esophagus
      is thought to be the result of long-standing gastroesophageal reflux disease and
      is known to be the most important risk factor for the development of esophageal
      adenocarcinoma. The natural history of Barrett's esophagus is not well known, but
      the annual incidence of invasive adenocarcinoma is estimated to be 0.5% (reported
      range, 0.2%-2.0%). This represents an increased risk for esophageal cancer of 30
      to 60 times higher than normal subjects. As for colorectal cancer, malignant
      degeneration is Barrett's esophagus is thought to occur through a continuum of
      histologic stages: metaplasia, dysplasia and neoplasia. Barrett's high-grade
      dysplasia (formerly referred to as carcinoma in situ) is the histologic stage of
      disease that immediately precedes the development of invasive carcinoma.
      CONCLUSIONS: Previously, Barrett's high-grade dysplasia patients were routinely
      referred for esophageal resection surgery based upon the assumption of inevitable
      progression to cancer, the high rate of undiagnosed synchronous cancers, and few
      treatment alternatives. Important developments in Barrett's high-grade dysplasia
      include recent publications regarding the natural history of Barrett's high-grade
      dysplasia and the regulatory approval for endoscopic ablation therapy using
      porfimer sodium photodynamic therapy (Photofrin PDT).

PMID- 15718861
TI  - Intestinal strongyloidiasis: recognition, management, and determinants of
      outcome.
AB  - Significant advances have occurred in our understanding of the biology,
      immunology, and immunopathology of the usually asymptomatic human infection by
      the intestinal parasite, Strongyloides stercoralis. Factors that increase the
      risk for the occurrence of symptomatic intestinal hyperinfection and/or often
      fatal disseminated strongyloidiasis have been better defined. The pathophysiology
      underlying these risk factors, whether disease-related or iatrogenically induced,
      is a compromised immune system leading to dysfunction of TH-2 helper cells. These
      specialized lymphocytes are central to maintaining the delicate balance that
      exists between the infected human host and the stabilized parasite. Recognition
      of risk factors that impair the function of TH-2 lymphocytes is essential to
      heightening the index of clinical suspicion enhancing earlier, accurate
      diagnosis, and the introduction of appropriate therapy. This review summarizes
      what is understood about infection by S. stercoralis; its focus will be on the
      epidemiology, diagnosis, clinical presentation patterns in the immunocompetent
      and immunocompromised human hosts, and recommended treatment regimens.

PMID- 15718862
TI  - Reduced medication dependency and improved symptoms and quality of life 12 months
      after enteryx implantation for gastroesophageal reflux.
AB  - BACKGROUND: The need is well recognized for additional data on endoluminal
      therapies for gastroesophageal reflux disease (GERD). This prospective
      multicenter clinical trial was designed to assess safety and effectiveness of
      Enteryx, a nonresorbable copolymer implanted into the lower esophagus, in
      reducing usage of proton pump inhibitors (PPIs) and improving reflux symptoms and
      quality of life. METHODS: Enteryx implantation was performed under fluoroscopic
      visualization without general anesthesia in 93 patients with symptomatic GERD
      responsive to and relapsing upon cessation of PPI therapy. Subjective and
      objective data were collected up to 12 months postprocedure. The criterion for
      treatment success was reduction in PPI dosage of > or =50%. RESULTS: At 12
      months, treatment success was attained in 86% (confidence interval, 77%-93%) of
      74 evaluable patients and elimination of PPI therapy in 65% (confidence interval,
      53%-76%). The treatment success rate by intent-to-treat analysis was 69%
      (confidence interval, 58%-78%). Reflux-related heartburn (P < 0.0001),
      regurgitation symptoms (P = 0.0005), and physical (P < 0.0001) and mental quality
      of life (P = 0.0012) scores improved. The most frequent complications were chest
      pain (77%), dysphagia/odynophagia (27%), and sensation of fever (26%).
      CONCLUSIONS: Enteryx implantation provides an effective and safe alternative for
      management of gastroesophageal reflux, reducing medication dependency and
      symptoms and enhancing quality of life.

PMID- 15718863
TI  - Motility abnormalities in esophageal body in GERD: are they truly related to
      reflux?
AB  - BACKGROUND: Esophageal motility abnormalities have been observed in patients with
      gastroesophageal reflux disease. GOALS: The aim of the present study was to
      determine if esophageal motor disorders in patients with a positive response to
      the omeprazole test are related to the existence of reflux or they are
      concomitant findings. STUDY: A 24-hour pH monitoring and a stationary manometry
      were performed on 128 patients: 49 of them had normal manometry, 31 hypotensive
      lower esophageal sphincter, 29 motor disorder in esophageal body, and 19
      hypotensive lower esophageal sphincter and motor disorder in esophageal body.
      RESULTS: We found an association between the presence of abnormal reflux and
      motor disorder in esophageal body (chi test; P < 0.05). However, ineffective
      esophageal motility was the disorder most strongly related to reflux, whereas the
      hypercontractile disorders were not clearly attributed to it. CONCLUSIONS:
      Esophageal manometric abnormalities should be considered cautiously before
      considering a motor disorder as a consequence of abnormal reflux.

PMID- 15718864
TI  - Ineffective esophageal motility in gastroesophageal erosive reflux disease and in
      nonerosive reflux disease: are they different?
AB  - BACKGROUND: In GERD patients, ineffective esophageal motility (IEM), a
      hypocontractile disorder, is the most common motor abnormality. IEM has been
      associated with reflux in both the supine and upright position, prolonged
      esophageal clearance, and delayed of bolus transport. IEM has been equally
      present in erosive and in nonerosive GERD. GOAL: Considering that reflux has been
      found to be more severe in erosive GERD than in nonerosive GERD patients and that
      IEM delays esophageal clearance, our hypothesis is that patients with erosive
      GERD have more severe IEM than those with nonerosive disease. STUDY: A
      retrospective review of consecutive manometries of patients with the chief
      complaint of heartburn and a diagnosis of IEM were performed, and patients with
      both erosive and nonerosive GERD were selected. According to the number of
      ineffective contractions, IEM was stratified into three groups: 30% to 40%, mild;
      50% to 60%, moderate; and greater than 60%, severe. We also registered the number
      of low amplitude, failed, and normal waves in each manometry of both groups. We
      evaluated 110 patients: 70 (64%) with erosive GERD and 40 (36%) with nonerosive
      GERD. The percentage of mild, moderate and severe IEM was similar in erosive and
      in nonerosive GERD patients, as well the number of low amplitude, failed or
      normal waves (P < 0.5). CONCLUSION: There were no differences between the
      severity of IEM in erosive and in nonerosive GERD patients.

PMID- 15718865
TI  - Ineffectiveness of routine abdominal radiography in patients with
      gastrointestinal hemorrhage admitted to an intensive care unit.
AB  - GOALS: To determine the utility of plain abdominal radiography in the initial
      evaluation of acute gastrointestinal (GI) hemorrhage in a medical intensive care
      unit. BACKGROUND: Plain abdominal radiographs are frequently used in the routine
      evaluation of patients with GI bleeding. The utility of these studies in the
      intensive care unit setting is unclear. STUDY: The study was a retrospective
      chart review of 71 adult subjects admitted to a medical intensive care unit with
      the diagnosis of GI bleeding. Subjects were excluded if they presented with
      peritoneal signs, received an abdominal CT scan in the 24 hours prior to
      admission, or were chronically treated with immunosuppressive medication.
      Subjects were divided into two cohorts based on whether or not they underwent
      plain abdominal radiography during the first hospital day. The primary study
      endpoints were hospital mortality, intensive care unit length of stay, and
      whether or not radiographic findings altered clinical management. RESULTS: Of the
      71 patients admitted with a diagnosis of GI bleeding (mean age 65.8 +/- 14.5
      years, 73.2% male), 56 (79%) had a plain abdominal radiograph performed. Subjects
      who had a plain film did not differ significantly from those who did not in age,
      gender, degree of anemia, degree of coagulopathy, or in severity of illness as
      measured by Acute Physiology and Chronic Health Evaluation (APACHE II) score.
      There was no statistically significant difference in hospital mortality or
      intensive care unit length of stay between patients who received plain films and
      those who did not. In no subject (0%; 95% confidence interval, 0%-5.4%) did
      abdominal radiography reveal an abnormality that altered clinical management.
      CONCLUSIONS: Based on our observations, plain films of the abdomen do not appear
      to alter clinical outcomes or management decisions for patients with GI bleeding
      and normal abdominal examinations who are admitted to the intensive care unit.

PMID- 15718866
TI  - Management of portal hypertension.
AB  - Complications of portal hypertension are the leading cause of death in patients
      with liver cirrhosis. Rational medical and endoscopic therapy is guided by a
      thorough understanding of the underlying pathophysiology of ascites, variceal
      formation and bleeding, hepatorenal syndrome, and hepatic encephalopathy. The
      pathophysiology of each clinical entity is reviewed followed by an evidence-based
      diagnostic and management algorithm.

PMID- 15718867
TI  - Is adiponectin involved in the pathogenesis of nonalcoholic steatohepatitis? A
      preliminary human study.
AB  - BACKGROUND: Animal studies have suggested that adiponectin may play a role in the
      pathogenesis of alcoholic and nonalcoholic fatty liver disease. Studies are
      limited that evaluated the role of adiponectin in the pathogenesis of
      nonalcoholic steatohepatitis (NASH). METHODS: To further our understanding of the
      role of adiponectin in the pathogenesis of NASH, the following studies were
      conducted. Serum adiponectin was measured and correlated with anthropometric and
      nutritional variables in 21 patients with biopsy-proven NASH and 19 age-, gender
      , body mass index-, and body fat-matched controls. The effect of a mixed meal on
      serum adiponectin levels in a subgroup of patients (n = 24) with NASH and
      controls was assessed. In a separate cohort, liver samples belonging to healthy
      (n = 11), steatotic (n = 12), and NASH (n = 12) patients were used to further
      explore the role of adiponectin by measuring the expression of adiponectin and
      adiponectin receptor (AdipoR2) mRNA. RESULTS: Patients with NASH had
      significantly lower levels of serum adiponectin than controls (4.9 +/- 2.7 vs.
      7.3 +/- 3.5 microg/mL, P = 0.02). While no significant correlation existed
      between serum adiponectin and anthropometric or nutritional variables, it was
      independently associated with age, high density lipoprotein, and triglycerides.
      Mixed meal had no effect on serum adiponectin either in patients with NASH or in
      controls. There was no expression of adiponectin mRNA in any of liver samples
      studied. However, AdipoR2 mRNA expression was higher in NASH than in steatotic
      and normal liver tissue. CONCLUSION: These data show that adiponectin may have a
      role in the pathogenesis of human NASH and should be investigated further.

PMID- 15718868
TI  - Association between smallpox vaccination and hepatitis C antibody positive
      serology in Pakistani volunteers.
AB  - GOALS: To determine whether the smallpox vaccination program has significantly
      contributed to the widespread prevalence of hepatitis C infection in Pakistan.
      BACKGROUND: Hepatitis C virus has become a worldwide pandemic and has especially
      devastated developing nations such as Pakistan. There continues to be an increase
      in fatalities due to hepatitis C-related cirrhosis in Pakistan. STUDY: We studied
      523 volunteers in the city of Lahore to determine whether the smallpox
      vaccination program, which ran from 1964 to 1982 in Pakistan, may be responsible
      for the national surge in hepatitis C viral infection, perhaps because of
      repetitive use of vaccination devices without proper sterilization or to
      contaminated vaccine contents. RESULTS: There was a significantly higher
      likelihood of hepatitis C antibody seroprevalence in individuals vaccinated for
      smallpox versus nonvaccinated individuals (21.0% vs. 4.6%, P < 0.001, age
      adjusted odds ratio, 3.39; 95% confidence interval, 1.36-8.46). Subjects with
      positive hepatitis C serology were also more likely to have a history of
      transfusions (19.2% vs. 9.0%, P = 0.01), but anti-HCV positive serology was not
      significantly associated with a history of surgery or dental procedures.
      Following adjustment for age, sex, and history of other conditions, including
      transfusion, the association between prior smallpox vaccination and hepatitis C
      antibody seroprevalence remained strong and highly significant (multivariate
      adjusted odds ratio, 6.11; 95% confidence interval, 2.58-14.51). CONCLUSION:
      These results suggest that the widespread prevalence of hepatitis C infection in
      Pakistan may be an unintended consequence of the country's smallpox vaccination
      program and that blood transfusion is also a significant risk factor.

PMID- 15718869
TI  - Comparing the outcomes of radiofrequency ablation and surgery in patients with a
      single small hepatocellular carcinoma and well-preserved hepatic function.
AB  - GOALS: To compare the efficacy of radiofrequency ablation (RFA) and surgical
      resection in a group of patients with a Child-Pugh score of 5 and a single HCC
      less than 4 cm in diameter. BACKGROUND: Radiofrequency ablation (RFA) has become
      a popular method for treatment of hepatocellular carcinoma (HCC) and has been
      applied as an alternative primary therapy to surgical resection. STUDY: We
      compared outcomes for 148 patients treated with RFA (n = 55) and those treated
      surgically (n = 93). RESULTS: The rate of local recurrence among patients in the
      RFA group was significantly higher than in the surgery group (P = 0.005), while
      the incidence of remote recurrence was similar between the two groups (P = 0.30).
      The cumulative 1- and 3-year overall survival rates (P = 0.24) and the cumulative
      1- and 3-year recurrence-free survival rates (P = 0.54) were not significantly
      different between the two groups. CONCLUSIONS: Despite a higher rate of local
      recurrence, RFA was found to be as effective as surgical resection for the
      treatment of single small HCC in patients with well-preserved liver function, in
      terms of the incidence of remote recurrence and the patients' likelihood of
      achieving overall and/or recurrence-free survival.

PMID- 15718870
TI  - Malignant serous cystic neoplasm of the pancreas: report of a case and review of
      the literature.
AB  - BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be
      benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical
      entity. CASE REPORT: We report the case of an 87-year-old woman with a serous
      microcystic neoplasm in the tail of the pancreas that behaved in a malignant
      fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum.
      The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm,
      and the patient underwent distal pancreatectomy with splenectomy and segmental
      colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which
      occupied the body and tail of the pancreas. Histologically, the tumor was
      indistinguishable from serous cystadenoma. However, the tumor had invaded
      surrounding tissues including the splenic vein, and there were splenic invasion
      and a regional lymph node metastasis. The postoperative course was uneventful.
      DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in
      which malignancy was histologically confirmed in the resected specimen. There are
      no reports of a negative outcome with complete resection of the tumor. Surgical
      treatment should be considered for serous cystic neoplasms, especially large
      ones, because of the malignant potential.

PMID- 15718871
TI  - Attitudes regarding Helicobacter pylori in Peru.

PMID- 15718872
TI  - Zenker's diverticulum: a contraindication for wireless capsule endoscopy?

PMID- 15718875
TI  - Benefits for employees with children with ADHD: findings from the Collaborative
      Employee Benefit Study.
AB  - Parents of most children with attention-deficit hyperactivity disorder (ADHD) are
      employed. Employers have interest in decreasing employee absenteeism and
      improving workplace productivity, partly through employee benefits. The authors
      interviewed employers to (1) determine how they view the needs of employees with
      children with ADHD and (2) identify benefits that might help employees with
      children with ADHD. The authors carried out a systematic interview study of
      mainly family-friendly, large employers in four U.S. urban markets (Boston,
      Cleveland, Miami, Seattle). Multidisciplinary interview teams used a protocol to
      gather basic company information, benefit philosophy, current insurance and other
      employee benefits, and knowledge of ADHD and its impacts on employees. Initially,
      the interview team and then the larger project team reviewed all protocols for
      common themes. The authors interviewed staff of 41 employers (human resource
      managers, work/life program directors, benefits directors). Only 15 of 41
      interviewees knew about ADHD, its prevalence, or its effects on parents. They had
      little knowledge of how differences in managed behavioral health may affect
      families' access to diagnostic and treatment services for ADHD, although most had
      experience with primary care management of depression among employees. Employers
      offer a variety of other benefits, including work/life and employee assistance
      programs, occasionally providing employees help with caring for a child with a
      mental health condition, on-site parent training programs, or assistance with
      child care. Other potentially useful employee benefits include flexible work and
      leave policies and information and referral services that can link parents with
      community programs. Although employers have limited awareness of ADHD and its
      potential effect on employees' work, this study identified opportunities to
      improve both health insurance and other benefits for employees with children with
      ADHD.

PMID- 15718876
TI  - Managing ADHD.

PMID- 15718877
TI  - Employee benefits for dependents with ADHD: an opportunity for improvement.

PMID- 15718878
TI  - Prolonged and unsoothable crying bouts in infants with and without colic.
AB  - ABSTRACT.: The authors sought to determine which features of early distress were
      "excessive" and specific to the first months of life as described by diary
      recordings. In a short-term, longitudinal, controlled study, total daily amount,
      frequency, and bout duration of fussing, crying, and unsoothable crying were
      derived from validated diaries kept by parents of infants with and without diary
      defined colic at 6 weeks and 5 months recruited from primary pediatrics
      practices. By definition, infants with colic demonstrated more distress at 6
      weeks, but they also had a much greater reduction in distress by 5 months and
      more distress during the fifth month. However, bout frequencies and bout
      durations showed different patterns. Bout duration was longer for the colic group
      only at 6 weeks; the difference completely disappeared by 5 months. Bout
      frequency was higher for the colic group at 6 weeks and 5 months, but the
      reduction across ages was similar in infants with and without colic. These
      patterns were true for all distress modalities (fussing, crying, and unsoothable
      crying). Unsoothable crying was present in significant amounts only at 6 weeks
      but virtually disappeared by 5 months. The authors conclude that prolonged
      distress bouts and unsoothable crying are specific to the first few months and
      more common, though not unique, in infants with colic. This implies that our
      understanding of colic may depend more on why these infants cry longer once
      started than what makes infants cry. These features of parental experience may be
      important in preventive efforts to reduce negative impacts of early increased
      crying such as shaken baby syndrome.

PMID- 15718880
TI  - Infant, mother, and contextual predictors of mother-very low birth weight infant
      interaction at 9 months of age.
AB  - This prospective study examined how characteristics of infants (i.e., birth
      weight and perinatal illness severity), mothers (i.e., anxiety and level of
      education), and the social context (i.e., maternal received and perceived
      helpfulness of support) related to mother-very low birth weight (VLBW) infant
      interaction in 72 dyads. Infant, mother, and contextual factors were assessed at
      3 and 9 months of age, and mothers and infants were observed in teaching
      interactions at 9 months. Dyads whose interaction was more sensitive and
      responsive included mothers who were better educated and less anxious at 3 months
      and reported higher perceived support at 3 months. The findings highlight the
      importance of maternal education and well-being in the parenting of VLBW infants.

PMID- 15718881
TI  - Use of videotaped interactions during pediatric well-child care to promote child
      development: a randomized, controlled trial.
AB  - The authors performed a randomized, controlled trial to assess the impact of the
      Video Interaction Project (VIP), a program based in pediatric primary care in
      which videotaped interactions are used by child development specialists to
      promote early child development. Ninety-three Latino children (51 VIP, 42
      control) at risk of developmental delay on the basis of poverty and low maternal
      education (none had completed high school) were assessed for cognitive and
      language development at age 21 months. Results differed depending on the level of
      maternal education; the VIP was found to have a moderate impact on children whose
      mothers had between seventh and 11th grade education (approximately 0.75 SD for
      cognitive development, 0.5 SD for expressive language) but little impact on
      children whose mothers had sixth grade or lower education.

PMID- 15718883
TI  - Attentional functioning and impulse control in cocaine-exposed and control
      children at age ten years.
AB  - Children with gestational cocaine exposure may be at risk of difficulties in
      attentional functioning and impulse control. We administered the Gordon
      Diagnostic System and subtests of the Halstead-Reitan Battery to inner-city
      children with (COC) and without (CON) gestational cocaine exposure at age 10
      years. Subtle differences were found between groups, with differences in Gordon
      Delay (Efficiency Ratio) and Gordon Distractibility (Total Commissions). With
      these two exceptions, children had similar performance, with both groups
      performing poorly. Attentional functioning and impulse control were also assessed
      in school. Teachers did not distinguish between COC and CON, although both groups
      presented behavioral problems. We conclude that gestational cocaine exposure may
      be associated with subtle problems in attention and impulse control, putting
      exposed children at higher risk of developing significant behavioral problems as
      cognitive demands increase.

PMID- 15718884
TI  - Temperament at 9 months of very preterm infants born at less than 29 weeks'
      gestation: the Epipage study.
AB  - The objective was to determine whether the temperament of very preterm singleton
      infants born before 29 weeks' gestation differs from their full-term counterparts
      at 9 months and to examine the influence of neurological sequelae on temperament
      in very preterm infants. The parents of very preterm infants from nine French
      regions and a group of full-term infants were sent the Infant Characteristics
      Questionnaire when the infants were 9 months old. The analysis included 266
      singleton very preterm infants from the same regions born before 29 weeks'
      gestation and 546 full-term singleton infants. There were no significant
      differences for the Difficult, Unadaptable, and Unpredictable scales between very
      premature and term infants. Very preterm infants had a slightly higher Dull scale
      score than term infants. After taking into account mother's age, duration of
      hospitalization, and cerebral lesions found on neonatal ultrasound scans, this
      difference was no longer significant. Among very premature infants, those with
      cerebral lesions as diagnosed by neonatal ultrasound scan were rated higher on
      the Dull and Unadaptable scales. Delays in development at 9 months were also
      related to higher Dull and Unpredictable scales. These data suggest that
      prematurity does not affect temperament ratings at 9 months as assessed by the
      mother. However, very preterm infants with neurological insults, documented by
      the neonatal cerebral ultrasound or by a delay in development, are rated higher
      by their mothers on the Dull, Unadaptable, and Unpredictable scales.

PMID- 15718885
TI  - Reformatting the 9-month Health Supervision Visit to enhance developmental,
      behavioral and family concerns.

PMID- 15718886
TI  - Conducting research on sensitive topics with adolescents: ethical and
      developmental considerations.
AB  - Promotion of adolescent health requires well-designed scientific studies that
      determine the prevalence of the problem of interest, identify risk and resilience
      factors, and evaluate methods for prevention and intervention. Many adolescent
      related health problems are typically considered sensitive by society (e.g.,
      sexual and substance use behaviors), thus further complicating the research
      process. Using the principles of the Belmont Report as its framework, this paper
      draws on developmental theories to discuss ethical issues specific to the conduct
      of research with adolescents. Our ability to use developmentally sensitive
      research practices will be enhanced by further understanding of issues associated
      with risk and benefit assessment by the adolescent, their parents, and
      institutional review boards, and by delineating ways to ensure that adolescent
      participants are adequately protected and have a developmentally affirming
      experience.

PMID- 15718888
TI  - Farm-related limb amputations in children.
AB  - The purpose of this study was to review results for children sustaining traumatic
      farm-related limb amputations. Farm machinery accidents were responsible for 12
      limb amputations among 260 consecutive childhood traumatic amputations. All
      amputations resulted in open, grade III-C fractures. Treatment consisted of
      operative debridement, antibiotics, possible replantation, and delayed wound
      closure. Mean follow-up was 8 years (range 1-20). Wound closure was achieved at a
      mean of 22 days (range 2-88) after an average of seven operative procedures
      (range, 2-11 operations). Skin grafting was necessary for 9 of the 12 limbs.
      Blood replacement was necessary for all but one patient. Initial wound cultures
      revealed polymicrobial contamination in all patients. Clinical infections
      developed exclusively and in all (6/6) patients who underwent attempted
      replantation. Replantation was considered in all cases and was attempted for six
      limbs but was successful in only two patients. Failure of replantation in four
      limbs was due to vascular insufficiency and infection. The surviving replanted
      limbs have continued to grow and have regained protective sensation. Prosthetic
      use ranges from excellent to intermittent among the 10 patients with permanent
      amputation. Farm-related limb amputations are among the most severe orthopaedic
      injuries sustained by children. Despite massive contamination, infection occurred
      only in replanted limbs. Because of the mutilating nature of these amputations,
      less than 20% can be successfully replanted.

PMID- 15718889
TI  - Traumatic hip dislocation in childhood.
AB  - Traumatic dislocation of the hip in childhood is uncommon and can be a
      consequence of minor trauma. The authors report a series of 35 dislocations in
      skeletally immature patients. Most were isolated posterior dislocations without
      acetabular lesions. In 75% of cases, reduction of the dislocation was easy. Nine
      children required surgery to remove interposed joint capsule and/or osteochondral
      fragments to achieve anatomic reduction. Outcomes were generally good, except in
      one patient in whom a displaced fracture of the femoral physis was followed by
      total head avascular necrosis. One case of partial necrosis had a satisfactory
      outcome. Epiphyseal necrosis, though uncommon, appeared to be inconsistent to
      prevent and hard to predict. Bone scan seems to be more effective than MRI for
      the detection of necrosis.

PMID- 15718890
TI  - Supracondylar fractures of the femur in children: closed reduction and
      percutaneous pinning of displaced fractures.
AB  - The authors reviewed nine children with 10 displaced supracondylar femoral
      fractures that were treated by closed reduction and percutaneous pinning. The
      average age of the patients was 8.3 years (range 5-13). After removal of the pins
      and plaster at 5 weeks, full range of movement was regained within 3 weeks. At
      late follow-up (average 7.4 years [range 4-10]), seven of the eight patients
      reviewed (nine fractures) had a satisfactory result. One patient had a valgus
      deformity of 6 degrees. There was no growth plate arrest and no leg length
      discrepancy. Intra-articular pin placement was avoided, considering the different
      synovial attachments on the medial and lateral sides. One patient developed a
      common peroneal nerve palsy, and therefore a cadaver study was performed to
      determine whether movement of the knee after pin placement affected the nerve.
      Although the lateral pin did tether the iliotibial band, the common peroneal
      nerve was not affected.

PMID- 15718891
TI  - Open reduction of displaced pediatric supracondylar humeral fractures through the
      anterior cubital approach.
AB  - The authors performed a retrospective review of the anterior cubital approach, an
      alternative exposure for displaced pediatric supracondylar fractures. Anatomic
      structures that hinder reduction, such as the brachialis muscle or joint capsule,
      and neurovascular tissues can be identified easily with this approach. Sixty-one
      children with displaced supracondylar humeral fractures were treated surgically
      with Kirschner wires using the anterior cubital approach between January 1996 and
      August 2002. The cohort comprised 35 boys and 26 girls with a mean age of 8.7
      years (range 3-13 years). Mean follow-up was 3.5 years (range 1-6 years).
      Preoperatively 13 children (21.3%) had a neurovascular insufficiency that
      required an exploration during the operation. All patients were reduced
      completely with full anatomic position. On follow-up, no patient had any scar
      formation or deformity or experienced any restricted motion. The authors conclude
      that the anterior cubital approach is very effective and is an option for the
      treatment of pediatric supracondylar humerus fractures without serious
      complications.

PMID- 15718892
TI  - Displaced olecranon apophyseal fractures in children with osteogenesis
      imperfecta.
AB  - Three boys with mild osteogenesis imperfecta (OI) who sustained eight apophyseal
      avulsion fractures of the olecranon were compared with four normal boys with a
      unilateral apophyseal fracture. The children with OI were younger (11 years 7
      months) than the normal children (14 years 3 months). All fractures were treated
      with tension band wiring (TBW). The contralateral elbow fractured 1 to 12 months
      later in the children with OI. Refractures occurred in two elbows, 6 to 16 months
      after the initial fracture and after TBW removal. One refracture presented late
      as a nonunion and was treated with bone grafting and plate fixation. None of the
      normal children experienced refracture after TBW removal. Good functional results
      and range of movement were achieved. Surgical treatment is recommended for all
      displaced fractures of the olecranon apophysis. There is a high risk of bilateral
      injury and a risk of refracture following removal of TBW in children with OI.

PMID- 15718893
TI  - Small-fragment wounds from explosive devices: need for and timing of fragment
      removal.
AB  - The management of soft tissue small-fragment wounds caused by bombs remains
      controversial. The authors analyzed the outcome of low-energy foreign body
      injuries in 10 pediatric victims of suicide bomber attacks treated in their
      institution over a 2-year period. Two died during primary surgery. The eight
      survivors underwent a total of 10 procedures for removal of foreign bodies.
      Average follow-up was 24.1 months. The indications for the procedures were
      analyzed by the time of their performance: immediate, as part of the primary
      emergency operation (n = 2); intermediate, within 2 weeks after injury (n = 3);
      and late, more than 2 weeks after injury (n = 5). The results showed that all
      operations performed for objective indications were done within the immediate or
      intermediate period, whereas those done for subjective reasons were all but one
      performed in the late period. By the final follow-up visit, all foreign bodies
      had been removed. In conclusion, fragment removal is best done during the primary
      procedure if it does not pose a significant risk of complications.

PMID- 15718894
TI  - Management of unstable/acute slipped capital femoral epiphysis: results of a
      survey of the POSNA membership.
AB  - There is limited literature regarding the treatment of unstable slipped capital
      femoral epiphysis (SCFE). The Evidence Analysis Work Group (EAWG) initiated a
      questionnaire assessing management of unstable SCFE by the members of the
      Pediatric Orthopaedic Society of North America (POSNA). All members were surveyed
      by e-mail and fax. The survey was accessible through the POSNA web site. One
      third of the members responded. Seventy-three percent of members used the
      "stable/unstable" classification, while 27% used the "acute/chronic" terminology.
      Thirty-one percent of respondents felt that an unstable SCFE is an emergency,
      while 57% felt that treatment could be on an urgent (<8 hours) basis. Fifty-seven
      percent reported use of a single threaded screw for fixation for an unstable
      SCFE, and 40.3% recommended two threaded screws. There seems to be agreement on
      methods of patient evaluation, but discrepancies remain in classification and
      fixation methods. The EAWG recommends development of multicenter studies to
      evaluate the treatment of unstable SCFE.

PMID- 15718895
TI  - Computer-assisted cannulated screw fixation for slipped capital femoral
      epiphysis.
AB  - In slipped capital femoral epiphysis (SCFE), cannulated screw fixation is a
      standard procedure. The aim of this study was to investigate the feasibility of a
      fluoroscopy-supported navigation system for screw fixation in SCFE. Using a
      fluoroscopy-enhanced navigation system, a cannulated screw fixation was performed
      in seven hips of four patients. The navigation system showed a high feasibility
      in instrument visualization and implant placing. The mean x-ray time was 6.2
      seconds. Initial experiences are very promising and show advantages of the
      fluoroscopy-supported navigation. Considerably reduced x-ray exposure for
      patients and surgeons is possible. In the future, further efforts will be
      necessary to develop navigation-specific instruments to enhance the precision of
      screw positioning.

PMID- 15718897
TI  - Hinged distraction of the adolescent arthritic hip.
AB  - From 1996 to 2000, 11 adolescents with hip joint arthritis secondary to
      osteonecrosis or idiopathic chondrolysis were treated with articulated hinged
      distraction arthroplasty. Indications for surgery were severe pain and limited
      ambulation. Charts and radiographs were reviewed. Clinical status was assessed
      preoperatively and at latest follow-up (mean 4.8 years after surgery) using
      criteria of pain, range of motion, and ambulation level. Ten patients showed
      improved clinical status, with seven having an excellent outcome and three a good
      outcome. One patient failed distraction. Mean joint space was 2.6 mm before
      surgery and 4.8 mm at latest follow-up. Average duration of fixator use was 4.4
      months. Four patients (36.4%) had complications. Articulated hip distraction was
      effective in eliminating pain, improving function, and preventing progressive
      degenerative changes in young patients' hips. It should be considered a salvage
      procedure for arthritic hips and an alternative to arthrodesis in this difficult
      to-treat group of patients.

PMID- 15718896
TI  - Extracapsular base of neck osteotomy versus Southwick osteotomy in treatment of
      moderate to severe chronic slipped capital femoral epiphysis.
AB  - The aim of this study was to evaluate the results of extracapsular base of neck
      osteotomy and Southwick osteotomy from clinical and radiologic points of view.
      This retrospective study included 35 hips in 33 patients who presented with
      moderate to severe slipped capital femoral epiphysis (SCFE) between 1995 and
      2001. These patients were divided into two groups according to the type of
      osteotomy: group A patients (n = 15) were treated by extracapsular base of neck
      osteotomy and group B patients (n = 18) were treated by modified Southwick
      osteotomy. Follow-up averaged 3.5 years (range 1-6 years). Clinical and
      radiologic evaluations were done before and after surgery. All patients were
      finally evaluated according to the modified Southwick criteria. Group A had 86.7%
      satisfactory results; group B had 90% satisfactory results. There was no
      statistically significant difference between the type of osteotomy and the final
      outcome. The authors believe that both types of osteotomy are equally safe and
      effective procedures, with minimal risks of avascular necrosis and chondrolysis,
      in the treatment of moderate to severe chronic SCFE.

PMID- 15718898
TI  - A simple modification of the Pavlik harness for unstable hips.
AB  - The Pavlik harness has been used in the treatment of developmental dysplasia of
      the hip for almost 60 years. During this time there has been little in the way of
      modification of the original design. In clinical practice it has an established
      role, but it is recognized to be less effective in more unstable hips, which are
      often associated with marked acetabular dysplasia. The authors present a simple
      modification that proved successful in three hips that were not stabilized in a
      Pavlik harness applied in the usual fashion.

PMID- 15718899
TI  - Clinical validation of the multiplier method for predicting limb length at
      maturity, part I.
AB  - To validate the accuracy of the multiplier method in predicting bone and limb
      maturity lengths, radiographs of 60 patients treated for lower limb length
      discrepancy were measured. Longitudinal limb length data were used to predict
      maturity lengths of non-epiphysiodesed normal bones and short bones. Mean errors
      for predictions were 1.1 cm (SD = 0.9) and 1.5 cm (SD = 1.3) for the multiplier
      method using chronologic age and skeletal age, respectively. Regression
      correlation values between multiplier method predictions and actual measurements
      were 0.93 using chronologic age and 0.90 using skeletal age. The multiplier
      method was more accurate than prediction using the Anderson et al growth charts.
      Mean error for limb length predictions was 2.5 cm for the multiplier method using
      chronologic age and 2.6 cm for the Moseley method. Although as accurate as the
      Moseley method, the multiplier method seems to be quicker and simpler to use and
      requires only one data point for predicting limb length at maturity.

PMID- 15718900
TI  - Clinical validation of the multiplier method for predicting limb length
      discrepancy and outcome of epiphysiodesis, part II.
AB  - To validate the accuracy of the multiplier method in predicting limb length
      discrepancy (LLD) and outcome of epiphysiodesis, radiographs of 60 patients
      treated for LLD were measured. Data generated were used to predict maturity
      lengths of epiphysiodesed limbs, bone length discrepancies at maturity, and LLD
      at maturity after epiphysiodesis (residual discrepancy) using the multiplier and
      Moseley methods. The multiplier method mean error for bone length discrepancies
      predictions was 0.6 cm (SD = 0.6). Mean error for predicting lengths of
      epiphysiodesed limbs was 1.6 cm (SD = 1.2) for both methods. Mean errors for
      predicting residual discrepancies were 0.9 cm for the multiplier method using
      chronologic age, 1 cm for the multiplier method using skeletal age, and 1.3 cm
      for the Moseley method. Mean error difference between the methods was significant
      (P = 0.0008). The multiplier method accurately predicts LLD and outcome of
      epiphysiodesis and is more accurate than the Moseley method in predicting LLD at
      maturity after epiphysiodesis.

PMID- 15718901
TI  - Measurement variance in limb length discrepancy: clinical and radiographic
      assessment of interobserver and intraobserver variability.
AB  - The purpose of this study was to assess interobserver and intraobserver
      variability in the assessment of clinical and radiographic measurement of lower
      limb length discrepancy. Clinical measurements included direct measurement with a
      tape measure from anterior superior iliac spine (ASIS) to lateral malleolus and
      ASIS to medial malleolus as well as block measurement. Slit scanogram
      radiographic measurement was also evaluated. All three clinical measurements had
      excellent reliability, but the relatively large mean differences and the large
      95% confidence intervals for clinical measurements limit the usefulness of these
      techniques. Slit scanogram measurement was the most reliable measurement
      technique. The intraobserver variance of direct slit scanogram measurement
      included intraclass correlation coefficient of 0.99, mean difference of 0.1 cm,
      and 95% confidence interval of 0.4 cm. Results were not influenced by patient age
      or body mass index. Slit scanogram measurement is the preferred method for
      assessment of limb length discrepancy. The direct slit scanogram measurement
      described in the text follows the mechanical axis line of the leg in the "at
      ease" standing position described by Paley. Direct measurement using a measuring
      tape on a full-length slit scanogram is more reliable than indirect measurement
      using horizontal lines drawn to a radiolucent ruler that is positioned by a
      technician, since direct measurement avoids errors due to nonparallel positioning
      of the limb relative to the ruler, and direct measurement also avoids errors due
      to non-horizontal lines drawn from standard bony landmarks to the ruler. The
      ideal radiographic measurement technique would have high reliability and accuracy
      and would minimize or eliminate radiation.

PMID- 15718902
TI  - The use of the Ilizarov technique in the treatment of upper limb deformity in
      patients with Ollier's disease.
AB  - Between 1997 and 2001 three children with Ollier's disease underwent treatment of
      five upper limb segments using the Ilizarov technique. Average length discrepancy
      was 8.4 cm in the arm and 4.5 cm in the forearm, but coexisting large angular
      deformities were the major problem in all the children. Full correction of the
      axial deviations was achieved in all children. Restoration of length was achieved
      in all arms, but residual forearm length discrepancy persisted. In four segments
      conversion of the abnormal cartilage into normal regenerate was observed on
      radiograms. The problems, obstacles, and complications are similar to those met
      in more usual lengthening procedures. The Ilizarov technique should be the
      treatment of choice in restoring the correct axis and length of a limb in
      patients with Ollier's disease.

PMID- 15718903
TI  - Leg length discrepancy in Legg-Calve-Perthes disease.
AB  - The purpose of this study was to determine the incidence of the leg length
      discrepancy (LLD) in Legg-Calve-Perthes disease and whether there is any
      correlation between LLD and age at onset, gender, type of treatment, and severity
      of disease. The study population consisted of 261 patients with unilateral
      involvement who had reached skeletal maturity at last follow-up. All hips were
      treated by containment methods (bed rest and traction in abduction, Petri cast,
      brace, varus osteotomy, Salter osteotomy, and shelf acetabuloplasty). The late
      results were classified according to the Stulberg classification. LLD was found
      in 33 patients and ranged from 1 to 5.2 cm (average 2.51 cm). The limb shortening
      was observed in Herring group B (average 2.18 cm) and C (average 2.82 cm) and was
      statistically significant more common in group C. The statistical analysis
      revealed no statistical difference between the age at onset, sex, and type of
      treatment with regard to LLD; nevertheless, patients in Herring group C with LLD
      were younger than patients in group B, and LLD was seen more often after varus
      osteotomy. The amount of residual shortening of the affected limb in Legg-Calve
      Perthes disease at the end of skeletal growth seems to depend on the extent of
      involvement and the presence of a growth arrest. A varus osteotomy produces more
      significant shortening than other methods of treatments. The age at the onset of
      symptoms and sex do not influence the amount of LLD, but early onset of the
      disease can result in more severe limb shortening.

PMID- 15718904
TI  - Knee reconstruction in syndromes with congenital absence of the anterior cruciate
      ligament.
AB  - The authors review their experience with four patients with congenital deficiency
      of the anterior cruciate ligament (ACL) who underwent surgical treatment of
      symptomatic knee instability at a mean age of 15.8 years (range 14-17 years).
      Associated syndromes included fibular hemimelia, congenital short femur, and an
      unspecified skeletal dysplasia. All patients had undergone multiple previous
      realignment and leg lengthening procedures and were skeletally mature at the time
      of the reconstruction. All four patients underwent ACL reconstruction, and one
      patient underwent concomitant posterolateral corner reconstruction. One patient
      required an osteochondral autograft transplant procedure in addition to ACL
      reconstruction. Hypertrophy of the meniscofemoral ligament of Humphrey was a
      consistent anatomic finding at surgery. The patients were followed for a mean of
      38 months (range 26-58 months) after the reconstruction. The mean preoperative
      Lysholm II score was 38 (range 28-56); the score had improved to a mean of 81
      (range 78-93) at the latest follow-up. The authors conclude that reconstructive
      surgery is a viable option for restoration of knee stability and function in
      appropriately selected patients with congenital ACL deficiency.

PMID- 15718905
TI  - Incidence of distal femoral and distal tibial deformities in infantile and
      adolescent blount disease.
AB  - The purpose of this study was to assess distal femoral and tibial deformity in
      patients with infantile and adolescent Blount disease. This was a retrospective
      review of patients at the authors' institution diagnosed with Blount disease.
      Thirty-eight patients (21 in the infantile group and 17 in the adolescent group)
      met the study criteria. Measurements of the anatomic lateral distal femoral angle
      (aLDFA), anatomic lateral distal tibial angle (aLDTA), and tibiofemoral angle
      (TFA) were made from long-leg radiographs. The results of the infantile and
      adolescent measurements were compared with each other and to a normal database.
      Intraobserver and interobserver error was determined. The adolescent aLDFA
      measurements were significantly greater (more varus) than for the infantile group
      and normal database. The aLDTA (ankle) measurements were not statistically
      different between the two groups, or from the normal database. Analysis of both
      intraobserver and interobserver error for the aLDFA and aLDTA showed good
      reliability.

PMID- 15718906
TI  - Treatment of congenital pseudarthrosis of the tibia: a multicenter study in
      Japan.
AB  - Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. To
      clarify the current situation in treatment, a multicenter study was carried out
      to obtain information on the results of CPT treatment. The objective of this
      study was to propose appropriate treatment guidelines for CPT. Records of 73
      patients with CPT who underwent surgical treatment were collected from 32
      hospitals. The modality of the treatment was 26 with Ilizarov technique, 25 with
      free vascularized fibular graft, 7 with a combination of the two techniques, 6
      with intramedullary nailing with free bone grafting, 5 plating with free bone
      grafting, and 4 with other treatments. Fifty-four procedures resulted in union, 7
      resulted in delayed union, 7 were left un-united, 1 underwent amputation, and the
      results were unknown in 4. According to the results of this study, the most
      acceptable methods of treatment of CPT are the Ilizarov method and the
      vascularized fibular graft.

PMID- 15718907
TI  - Use of the foot abduction orthosis following Ponseti casts: is it essential?
AB  - The purpose of this study was to evaluate the need for the use of a foot
      abduction orthosis (FAO) in the treatment of idiopathic clubfeet using the
      Ponseti technique. Forty-four idiopathic clubfeet were treated with casting using
      the Ponseti method followed by FAO application. Compliance was defined as full
      time FAO use for 3 months and part-time use subsequently. Noncompliance was
      failure to fulfill the criteria during the first 9 months after casting. Feet
      were rated according to the Dimeglio and Pirani scoring systems at initial
      presentation, at the time of FAO application, and at 6 to 9 months of follow-up.
      At the time of application, no significant differences in scores were found
      between the groups. At follow-up, the compliant group's scores were significantly
      (P < 0.01) better than those of the noncompliant group. From the time of
      application to follow-up, for the compliant group, the Dimeglio scores improved
      significantly (P = 0.005). For the noncompliant group, the Dimeglio scores
      deteriorated significantly (P = 0.001). The feet of patients compliant with FAO
      use remained better corrected than the feet of those patients who were not
      compliant. Proper use of FAO is essential for successful application of the
      Ponseti technique.

PMID- 15718908
TI  - Treatment of idiopathic clubfoot utilizing botulinum A toxin: a new method and
      its short-term outcomes.
AB  - A pivotal point in most clubfoot management protocols is Achilles tendon
      lengthening or tenotomy to address hindfoot deformity. The effectiveness of
      botulinum A toxin (BTX-A) in attenuating the function of the triceps surae muscle
      complex as an alternative to tenotomy was investigated. Fifty-one patients with
      73 idiopathic clubfeet were recruited. Outcome measures included surgical rate,
      Pirani clubfoot score, ankle dorsiflexion with knee in flexion and extension, and
      recurrences. Patients were divided according to age: group 1 (<30 days old) and
      group 2 (>30 days and <8 months old). Ankle dorsiflexion in knee flexion and
      extension remained above 20 degrees and 15 degrees, respectively, and Pirani
      scores below 0.5 following BTX-A injection for both groups. One of the 51
      patients required limited posterior release and 9 patients required repeat
      manipulation and casting plus or minus BTX-A injection. The use of BTX-A as an
      adjunctive therapy in the noninvasive approach of manipulation and casting in
      idiopathic clubfoot is a safe and effective treatment.

PMID- 15718909
TI  - Gait analysis in children with severe clubfeet: early results of physiotherapy
      versus surgical release.
AB  - Ninety children between the ages of 2 and 3 years with 127 clubfeet underwent
      gait analysis. Fifty-one feet had undergone posteromedial releases, 52 feet had
      no surgery following correction of the deformity using the French physical
      therapy program, and 24 feet had either tendo Achilles lengthening or posterior
      releases following physical therapy. Persistent internal rotation of the foot
      during gait was the most frequent gait disturbance and was seen in all treatment
      groups. Limited ankle dorsiflexion was most common in the nonoperated feet, while
      calcaneus deformity occurred in the posteromedial release group. Ankle motion
      during gait was normal in 54% of nonoperated feet compared with 39% of feet that
      had posteromedial releases. While gait abnormalities were common in all clubfeet,
      fewer deviations were documented in feet treated with physical therapy that did
      not require surgery. Aggressive release leads to a higher likelihood of abnormal
      ankle motion and internal rotation during gait.

PMID- 15718910
TI  - Foot deformities in children with hereditary motor and sensory neuropathy.
AB  - The authors reviewed 104 feet from 52 consecutive children with hereditary motor
      and sensory neuropathy (HMSN) seen for the first time in clinics in two pediatric
      institutions between 1996 and 2003. Sixty-nine feet had a cavovarus deformity, 23
      feet had a planovalgus deformity, and 12 feet had no significant deformity. All
      cases with deformity had bilateral involvement, and of those with deformity, only
      45% had symmetric involvement. In HMSN I, III, IV, V, and X-linked HMSN,
      cavovarus was the most common deformity. However, in HMSN II, 55% of feet had a
      planovalgus deformity, 36% had a cavovarus deformity, and 9% had no deformity. In
      all, 43 feet underwent surgery of some type. Surgery, and in particularly
      combined bony and soft tissue procedures, was performed much more frequently on
      feet with cavovarus than planovalgus deformities. Soft tissue surgery alone was
      performed at an earlier age than combined bony and soft tissue surgery.

PMID- 15718911
TI  - Superficial versus deep transfer of the posterior tibialis tendon.
AB  - Transfer of the posterior tibialis tendon to the dorsum of the foot is a commonly
      performed procedure in conditions that weaken ankle dorsiflexors and evertors,
      resulting in equinovarus foot deformities. When transferring the tendon, surgeons
      have the choice of routing the tendon deep to the extensor retinaculum or
      superficial to it. This study compares the biomechanics of these two routing
      methods. Seven cadaveric lower limbs were tested by applying known forces to the
      transferred posterior tibialis tendon. Resultant kinematics indicated that
      passing superficial to the retinaculum resulted in a significantly more efficient
      motion than transfer deep to the retinaculum.

PMID- 15718912
TI  - Correlation of foot radiographs with foot function as analyzed by plantar
      pressure distribution.
AB  - The goal of this study was to correlate radiographic measurements to the dynamic
      plantar pressure of the residual clubfoot. This was done by comparing radiographs
      and EMED plantar pressure results in 61 idiopathic clubfeet in 39 children at an
      average of 8 years after complete subtalar release. Radiographic measures were
      obtained using the standard method outlined by Simons, and pressure data were
      collected for eight regions of the foot. Pearson correlation analysis was
      performed and the most significant correlation was found between the
      calcaneal/first metatarsal angle in the lateral radiographic view (r = 0.72) and
      the midfoot contact area. In the anteroposterior view there was mild correlation
      between the talus/first metatarsal angle and both the peak pressure and plantar
      contact area. The results of this study indicate that radiographs used in concert
      with dynamic plantar pressure analysis will provide a more complete assessment of
      the corrected clubfoot.

PMID- 15718913
TI  - Cervical spine issues in Down syndrome.

PMID- 15718914
TI  - The pseudoacetabulum.

PMID- 15718915
TI  - Dominance of high-producing interleukin 6 and low-producing interleukin 10 and
      interferon gamma alleles in glucose-6-phosphate dehydrogenase-deficient trauma
      patients.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a condition associated with
      malaria resistance, is a common genetic polymorphism. Decreased interleukin (IL)
      10 production was demonstrated in vivo and in vitro in the African and
      Mediterranean forms of G6PD deficiencies. We hypothesized that low-producing IL
      10 alleles are more abundant in the G6PD-deficient than nondeficient population.
      One hundred eleven men with African American ancestry were tested for G6PD
      deficiency (Type A-202/376) and for the cytokine gene promoter polymorphisms of
      IL-10 (-1082 G/A, -819 T/C, and -592 A/C), tumor necrosis factor (TNF)-alpha (
      308 G/A), transforming growth factor (TGF)-beta1 (C/T codon 10 and C/G codon 25),
      IL-6 (-174 G/C), and interferon (IFN)-gamma (+874 A/T). There were no differences
      in the allele frequencies for TNF-alpha, IL-6, or TGF-beta1 between the G6PD
      deficient and nondeficient population. In contrast, the low-producing IL-10
      alleles (-592A) and low-producing IFN-gamma (+874A) allele frequencies were
      greater in G6PD-deficient than nondeficient samples (P = 0.035 and 0.009).
      Seventy-one percent of G6PD-deficient and 50% of nondeficient samples carried the
      high-producing IL-6(G) allele with low-producing IL-10(A) allele (P = 0.03).
      Furthermore, 95% of deficient and 81% of nondeficient samples carried the IL-6(G)
      allele together with low-producing IFN-gamma(A) allele (P = 0.017). These
      investigations indicate a predominant presence of high-producing IL-6 alleles
      together with low-producing IL-10 and IFN-gamma alleles in individuals with
      ancestry from malaria-endemic regions. The frequency of low-producing IL-10
      genotypes is greater in the G6PD-deficient compared with nondeficient patients.
      The fact that these genetic differences are preserved in the current African
      American G6PD-deficient population indicates their potential role in
      pathophysiological processes in the absence of the selective pressure caused by
      tropical diseases.

PMID- 15718916
TI  - Selective management of cardiovascular dysfunction in posttraumatic SIRS and
      sepsis.
AB  - Cardiovascular dysfunction associated with the systemic inflammatory response
      syndrome (SIRS) is caused by a combination of decreased myocardial contractility
      and low vascular resistance. The contribution of each of these components can be
      determined at the bedside, and directed therapy can be appropriately initiated.
      Over an 8-month period of time, 23 consecutive patients who experienced
      posttraumatic SIRS while still being monitored with a volumetric pulmonary artery
      catheter (PAC) were prospectively evaluated. Ventricular pressure-volume diagrams
      were constructed to quantify myocardial contractility and afterload. In a
      resuscitation protocol, dobutamine was administered to patients with an isolated
      decrease in contractility, and dopamine or epinephrine was instituted for the
      combination of reduced contractility and afterload. Variables describing
      cardiovascular function were measured at the time of resolution of initial shock
      resuscitation (BASE), at the onset of SIRS (ONSET), and after administration of
      inotropic or vasoactive agents (TREAT). ONSET was associated with a significant
      decrease in left ventricular power (LVP) (362 +/- 96 to 235 +/- 55
      mmHg.L/min/m(2), P < 0.00001) and stroke work index (SWI) (4670 +/- 1213 to 3060
      +/- 848 mmHg.mL/m, P < 0.00001) from BASE. Sixteen patients (70%) demonstrated
      predominantly decreased contractility, which returned to near BASE values after
      the administration of dobutamine. The remaining seven patients (30%) had both
      decreased contractility and afterload, which was treated with dopamine or
      epinephrine. LVP and SWI significantly increased (235 +/- 55 to 328 +/- 77
      mmHg.L/min/m(2), P < 0.00001, and 3060 +/- 848 to 4554 +/- 1423 mmHg.mL/m(2), P <
      0.00001, respectively) on the initiation of directed therapy. Specific
      cardiovascular abnormalities can be identified at the bedside, and this
      information can guide pharmacologic management. Directed therapy improves
      cardiovascular function.

PMID- 15718917
TI  - Enhanced enzymatic degradation of tryptophan by indoleamine 2,3-dioxygenase
      contributes to the tryptophan-deficient state seen after major trauma.
AB  - Decreased lymphocyte proliferation, lymphopenia, immunodepression, and
      opportunistic infections are common after major trauma. Early alimentation in
      these patients corrects lymphopenia, enhances immunity, and reduces the incidence
      of infections, but the underlying mechanisms are poorly understood. Tryptophan is
      essential for the production and function of rapidly proliferating cells such as
      lymphocytes. Tryptophan is enzymatically degraded by indoleamine 2,3-dioxygenase
      (IDO), whose activity is solely dependent on expression of interferon-gamma (IFN
      gamma). Because increased expression of IFN-gamma has been reported in trauma
      patients, we investigated whether enhanced IDO-mediated tryptophan degradation is
      associated with lymphopenia and poor outcomes after major trauma. The incidence
      of bacteremic sepsis (BS), adult respiratory distress syndrome (ARDS), multiple
      organ dysfunction/failure syndromes (MODS/MOF), and death was prospectively
      documented in 22 trauma patients with a mean ISS of 24.9 +/- 2.2. Sequential
      blood samples were obtained from admission through postinjury day 10. Five
      patients developed BS, three of whom developed ARDS; two of the three ARDS
      patients developed MOF and died on day 10. Trauma patients had significantly
      lower tryptophan levels (days 1-10), higher kynurenine:tryptophan ratios (days 1
      2), and fewer lymphocytes (days 1-4) than healthy volunteers (P < 0.05). Although
      patients with poor outcomes (i.e., BS, ARDS, MOF, and death) had significantly
      lower tryptophan levels and greater lymphopenia on several days after injury, the
      sample size was too small to draw any definitive conclusions. These data indicate
      that decreased plasma tryptophan levels and lymphopenia typically occur after
      major trauma. A concomitant increase in kynurenine suggests that the observed
      tryptophan deficiency is caused, in part, by IDO-mediated tryptophan degradation.

PMID- 15718918
TI  - Expression of elastase on polymorphonuclear neutrophils in vitro and in vivo:
      identification of CD11b as ligand for the surface-bound elastase.
AB  - Elastase is a major serine protease of polymorphonuclear neutrophils (PMN). On
      activation of PMN, the preformed protein is mobilized from intracellular stores
      and, depending on the activating conditions, is either released into the
      supernatant or is bound to the cell surface. By a variety of methods, including
      uptake and crosslink studies, as well as confocal laser scan microscopy, we now
      provide evidence that elastase binds to the beta(2)-integrin CD11b and induces a
      conformational alteration of CD11b, apparent as expression of a neodeterminant.
      Similarly to the in vitro data, elastase surface expression and conformational
      alterations of CD11b were seen on PMN of patients with Staphylococcus aureus
      induced localized infection, particularly on PMNs recovered from the infected
      site. The presence of elastase at the site of inflammation is in keeping with its
      presumed role in leukocyte trafficking and host defense. On the other hand,
      because of its potential for degrading extracellular matrix proteins, elastase
      could participate in localized tissue damage as it occurs in severe S. aureus
      infection.

PMID- 15718919
TI  - Glucan phosphate treatment attenuates burn-induced inflammation and improves
      resistance to Pseudomonas aeruginosa burn wound infection.
AB  - These studies evaluated the effects treatment with glucan phosphate, a soluble
      polysaccharide immunomodulator, on the inflammatory response induced by burn
      injury and on resistance to Pseudomonas aeruginosa burn wound infection. Mice
      were exposed to 35% total body surface area burns and were resuscitated with
      lactated Ringer's (LR) solution alone or LR supplemented with glucan phosphate
      (40 mg/kg). Glucan phosphate treatment attenuated burn-induced expression of
      interleukin (IL)-1beta, IL-6, and IL-10 mRNAs in spleen, lung, and heart. Plasma
      concentrations of IL-1beta, IL-6, macrophage inflammatory protein (MIP)-2, and IL
      10 were also decreased in burned mice treated with glucan phosphate compared with
      vehicle-treated controls. Early postburn mortality was not significantly
      different between control (20%) and glucan phosphate-treated (10%) mice, but
      there was a small improvement in acid-base balance in the glucan phosphate
      treated group. Mice received a second injection of glucan phosphate or LR on day
      4 postburn and were infected by topical application of P. aeruginosa to the burn
      wound on day 5. Glucan phosphate treatment significantly improved survival in
      mice exposed to P. aeruginosa burn wound infection. The improved survival
      correlated with lower bacterial burden in the burn wound, attenuated production
      of proinflammatory cytokines, and enhanced production of Th1 cytokines. These
      studies show that glucan phosphate treatment attenuates burn-induced inflammation
      and increases resistance to P. aeruginosa burn wound infection in an experimental
      model of burn injury.

PMID- 15718920
TI  - Inhibitors of poly (ADP-ribose) polymerase ameliorate myocardial reperfusion
      injury by modulation of activator protein-1 and neutrophil infiltration.
AB  - During myocardial reperfusion injury, oxidative stress induces DNA damage and
      activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1),
      resulting in cardiovascular dysfunction. In this study, we investigated the
      biological effects and the molecular mechanisms of two structurally unrelated
      selective inhibitors of PARP-1, 3-aminobenzamide (3-AB) and 1,5
      dihydroxyisoquinoline (-DIQ), in an in vivo model of myocardial ischemia and
      reperfusion. Male Wistar rats were subjected to 30 min of occlusion followed by
      reperfusion (up to 24 h) of the left anterior descending coronary artery. In
      vehicle-treated rats, ischemia and reperfusion induced extensive myocardial
      damage and marked neutrophil infiltration (as indicated by myeloperoxidase
      activity). Caspase 3 was maximally activated within 15 to 30 min after
      reperfusion, suggesting the occurrence of apoptosis. These inflammatory events
      were associated with activation of the transcription factor activator protein-1
      (AP-1) in the reperfused hearts. Treatment of the rats with the PARP-1
      inhibitors, 3-AB or 1,5-DIQ, reduced myocardial damage, neutrophil infiltration,
      and caspase activation. This cardioprotection was associated with reduction of AP
      1 activation. Furthermore, in in vitro cytokine-stimulated human endothelial
      cells, expression of intercellular adhesion molecule 1, vascular cellular
      adhesion molecule 1, and P- and E-selectin was significantly reduced by treatment
      with 3-AB or 1,5-DIQ. On the contrary, in vivo or in vitro treatment with
      nicotinic acid, a chemical analogue of PARP inhibitors, which lacks the ability
      to inhibit the catalytic activity of PARP-1, was unable to afford any protective
      effect and to prevent activation of AP-1. Our data demonstrate that inhibition of
      catalytic activity of PARP-1 may provide cardioprotection by regulating stress
      induced signal transduction pathways.

PMID- 15718921
TI  - Thermoregulatory set point decreases after hemorrhage in rats.
AB  - Hemorrhage in rats causes a drop in body core temperature that is proportional to
      the hemorrhage volume. We tested the hypothesis that the hemorrhagic hypothermia
      is due to a downward shift in the thermoregulatory set point. If so, rats
      subjected to hemorrhage would prefer a cooler ambient temperature to enhance heat
      loss during the posthemorrhage period. Male Sprague-Dawley rats were fitted with
      carotid arterial catheters and biotelemetry temperature probes. Two days later,
      rats were placed in a temperature gradient chamber that allowed the rat to move
      between ambient temperatures of 15 degrees C to 40 degrees C. Rat location within
      the gradient was recorded as the selected ambient temperature. After 48 h, a 24
      mL/kg hemorrhage was induced via the carotid cannula followed by a 24-h recovery
      period in the gradient. Body core and selected ambient temperatures significantly
      decreased after hemorrhage. Within 50 min, selected ambient temperature decreased
      by 11 degrees C, and returned to normal 100 min after hemorrhage. Within 80 min
      after hemorrhage, core temperature decreased by 2.3 degrees C, and returned to
      normal by 8 h after hemorrhage. Expanded analysis of the first hour after
      hemorrhage showed that reduction in selected ambient temperature preceded the
      drop in body core temperature. Importantly, the decrease in selected ambient
      temperature persisted even during the peak decrease in body core temperature.
      These results indicate that a decrease in thermoregulatory set point contributes
      to the drop in body core temperature after hemorrhage.

PMID- 15718922
TI  - Hemorrhage- and resuscitation-related alterations in gastrointestinal
      circulation: effect of a low dose of L-NMMA.
AB  - The gastrointestinal tract, including its mucosal barrier, is most sensitive to
      ischemic insults. The present study was conducted to evaluate hemorrhage- and
      resuscitation-related regional alterations in gastrointestinal circulation in
      presence or absence of a low dose of N(G)-monomethyl-L-arginine (L-NMMA), a
      nonspecific nitric oxide synthase inhibitor. Organ-specific circulation was
      studied using the colored microsphere technique in rats subjected to prolonged
      hemorrhagic shock (180 min) followed by resuscitation with or without L-NMMA (2
      mg/kg body weight) treatment at the end of resuscitation. We found an initial
      distal gradient in the intestinal blood flow with the highest rate in duodenum
      followed by jejunum, ileum, and colon. Hemorrhage resulted in the highest
      decrease in gastric blood flow. Resuscitation restored circulation in the
      intestinal tract to baseline levels except for gastric blood flow. L-NMMA
      treatment after completion of resuscitation did not deteriorate gastrointestinal
      blood flow. Our data show (a) a distal gradient in the intestinal blood flow from
      duodenum to colon, (b) that hemorrhage and resuscitation cause different degrees
      of alteration in gastric and intestinal blood flow, (c) that gastric perfusion
      does not recover after resuscitation, predisposing to further organ damage, and
      (d) that a low dose of L-NMMA does not deteriorate intestinal circulation in rats
      subjected to hemorrhage and resuscitation.

PMID- 15718923
TI  - Ringer's ethyl pyruvate in hemorrhagic shock and resuscitation does not improve
      early hemodynamics or tissue energetics.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of
      hemorrhagic shock. Ethyl pyruvate, a derivative of pyruvate and a proposed oxygen
      radical scavenger, is attractive as a possible resuscitation fluid. We
      investigated whether resuscitation with lactated Ringer's (LR) containing ethyl
      pyruvate (REP) had any hemodynamic or tissue energetic benefits compared with LR
      alone for hemorrhagic shock. Hemorrhagic shock was induced in splenectomized pigs
      via inferior vena cava cannula. After 90 min of shock, animals were resuscitated
      in a stepwise fashion with LR or REP (30 mg/kg/dose, given as 1.5 mg/mL in LR) at
      20 cc/kg/step for four steps. Data collected during this experiment included
      physiologic and hemodynamic parameters, near-infrared reflectance spectroscopy
      measurements of tissue hemoglobin oxygen (StO(2)) of the stomach, liver, and hind
      limb, and nuclear magnetic resonance phosphorus spectra of the liver and hind
      limb at each time point. In both resuscitative groups, heart rate, and lactate
      and pyruvate values increased during shock and began to drop toward baseline
      values during resuscitation. Mean arterial pressure, oxygen delivery, and oxygen
      consumption decreased during shock and increased toward baseline levels during
      the resuscitative process. There were no significant changes in physiologic
      parameters between the LR- and REP-resuscitated animals. There was a
      significantly lower stomach StO(2) and hind limb cellular cytoplasmic pH during
      later resuscitative endpoints in REP-resuscitated animals. The clinical
      significance of these findings are unclear. There is no short-term hemodynamic or
      tissue energetic advantage to using REP as a resuscitation fluid when compared
      with LR. Long-term outcome studies are needed to further evaluate any potential
      benefits of use of REP in hemorrhagic shock.

PMID- 15718924
TI  - Epinephrine protects against severe acute gastric bleeding in rats: role of
      nitric oxide and glutathione.
AB  - The aim of this study was to examine the effect of the systemic administration of
      epinephrine against severe acute gastric bleeding in rats. Epinephrine decreased
      gastric hemorrhage not only before but also after lipopolysaccharide-induced
      severe acute gastric bleeding. Epinephrine ameliorated severe gastric hemorrhage
      and decreased gastric mucosal lipid peroxidation through alpha- and beta
      adrenoceptors. Epinephrine modulated alpha-adrenoceptors to increase the levels
      of gastric mucosal nitric oxide and glutathione. Nitric oxide synthase inhibitors
      potently reversed the effects of epinephrine on gastric mucosal glutathione.
      Thus, epinephrine might act through alpha-adrenoceptors to increase the levels of
      gastric mucosal nitric oxide and glutathione and thus protect against severe
      acute gastric bleeding in rats.

PMID- 15718925
TI  - Ischemic preconditioning protects against gut dysfunction and mucosal injury
      after ischemia/reperfusion injury.
AB  - Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and
      impairs gut function. Ischemic preconditioning (IPC) has been shown to protect
      organs against IR injury. We hypothesized that IPC protects the gut from IR
      injury. Rats were randomized to a sham group, a sham early IPC + IR group (sham
      IPC + SMA occlusion for 30 min and 6 h of reperfusion), an early IPC + IR group
      (IPC, three cycles of SMA occlusion for 4 min and reperfusion for 10 min)
      followed immediately by SMA occlusion for 30 min and 6 h of reperfusion), a sham
      24-h group, a sham late IPC + IR group (sham IPC followed by additional
      reperfusion for 24 h + SMA occlusion for 30 min and 6 h of reperfusion), and a
      late IPC + IR group (IPC protocol followed by additional reperfusion for 24 h,
      and then SMA occlusion for 30 min followed by 6 h of reperfusion). At 6 h,
      transit was determined and expressed as the mean geometric center. Ileum was
      harvested for assessment of mucosal injury and myeloperoxidase (MPO) activity.
      Tissue water was determined using the wet-to-dry weight ratio to assess gut
      edema. Early IPC + IR significantly improved transit (3.9 +/- 0.2), decreased MPO
      levels (3 +/- 2), and lessened mucosal injury (1.2 +/- 0.3) compared with animals
      subjected to sham early IPC + IR (transit, 2.9 +/- 0.2; MPO levels, 9 +/- 1;
      mucosal injury, 3.0 +/- 0.6). Late IPC + IR also improved transit (6.0 +/- 0.4)
      and decreased MPO levels (1 +/- 1) compared with sham late IPC + IR (transit, 4.4
      +/- 0.2; MPO levels, 8 +/- 1), however, there was no difference in the mucosal
      protection between late IPC + IR (1 +/- 0.3) and sham late IPC + IR (1 +/- 1).
      Our results suggest that early and late IPC improves intestinal dysfunction,
      decreases inflammation, and provides mucosal protection in the intestine after
      IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both
      phases of IPC can potentially be useful in the clinical setting of surgical
      patient care.

PMID- 15718926
TI  - delta2 opioid receptor agonist facilitates mean arterial pressure recovery after
      hemorrhage in conscious rats.
AB  - delta opioid receptor agonists exert potent hemodynamic effects under ischemic
      conditions. This study was designed to assess the cardiovascular effects of
      Deltorphin-D(variant) (Delt-D(var)), a selective delta(2) opioid receptor
      agonist, in conscious, freely moving male rats during the posthemorrhage,
      recompensatory phase of a hemorrhagic trauma. Rats were fitted with femoral
      arterial and venous catheters for measurements of mean arterial pressure (MAP),
      heart rate (HR), and intravenous (i.v.) injections of isotonic saline, 1 mg/kg
      Delt-D(var), or 2 mg/kg Delt-D(var). During hemorrhaging, 30% (approximately 5
      mL) of total blood volume was collected from the arterial catheter. MAP-HR was
      fitted to a logistic equation to determine baroreceptor reflex properties.
      Hemorrhaged rats progressed through three distinct phases: compensation,
      decompensation, and recompensation. Saline and 1 mg/kg Delt-D(var) rats treated
      posthemorrhage had similar MAP and HR after hemorrhage. In contrast, 2 mg/kg Delt
      D(var) administered after hemorrhaging led to a faster and more complete recovery
      of MAP than compared with the other groups. In hemorrhaged rats, the average HR
      gain (bpm/mmHg) after 2 mg/kg Delt-D(var) treatment was greater and the BP(50)
      (BP at one-half the HR range) was significantly lower than after saline
      treatment. The results show that after hemorrhage, during the recompensatory
      period, stimulation of delta(2) opioid receptors leads to improved MAP, and this
      recovery may involve a change in baroreflex sensitivity.

PMID- 15718927
TI  - Cardiovascular effects of NA+/H+ exchanger inhibition with BIIB513 following
      hypovolemic circulatory shock.
AB  - Na(+)/H(+) exchange (NHE) is involved in the myocardial injury that occurs during
      ischemia and reperfusion. The goal of the present study was to investigate the
      role of NHE in hypovolemic circulatory shock by using a potent NHE-1 selective
      inhibitor BIIB513. Acute rapid hemorrhage was induced in 14 pigs by bleeding (30
      mL/kg over 30 min). Seven pigs were used as saline control. Seven other pigs
      received 3 mg/kg BIIB513 at 30 min after hemorrhage. Each experiment consisted of
      2 h of hypovolemia followed by 2 h of fluid resuscitation. One control animal
      died before the experiment was completed. Six other control animals survived the
      entire experiment. In contrast, all the BIIB513 treated animals survived the
      entire protocol. Acute rapid blood loss resulted in impaired myocardial
      performance as well as severe hemodynamic and metabolic alterations. NHE blockade
      attenuated the hypovolemic hypotension and improved myocardial performance. NHE
      blockade also attenuated the metabolic acidosis, improved tissue oxygen delivery,
      and improved cardiac function from resuscitation. The circulating levels of
      creatine phosphokinase (CPK) and cardiac troponin-I were significantly lower in
      the BIIB513 treatment group. These results suggest that NHE activation plays an
      important pathophysiological role in hypovolemic circulatory shock, and NHE-1
      blockade is a powerful intervention to improve cardiovascular outcomes of
      resuscitation from prolonged hypovolemic circulatory shock.

PMID- 15718928
TI  - Cobalt protoporphyrin protects against hepatic parenchymal injury and
      microvascular dysfunction during experimental rhabdomyolysis.
AB  - Although heme is necessary in many life-sustaining functions, its overwhelming
      systemic release with rhabdomyolysis (RM) is believed to be the cause of
      subsequent organ injury and dysfunction. We investigated the acute effects of
      experimental RM on hepatic parenchymal viability and microvascular function in
      vivo, while also determining the impact of cobalt protoporphyrin (CoPP) on its
      outcome. With a murine model of RM induced by hind limb glycerol administration
      (11.5 microL/g, i.m.), we show that plasma heme is elevated as early as 30 min
      after hind limb glycerol. However, significant hepatic heme accumulation did not
      occur until 3 h later, with a return to basal levels by 6 h. Using in vivo
      digital microscopy, hepatic parenchymal viability and microvascular function were
      found to be significantly compromised by 3 h of RM. Moreover, this response
      included the upregulation of hepatic heme oxygenase protein expression and
      activity. The administration of CoPP (5 mg/kg, i.p.) protected hepatic
      parenchymal and microvascular integrity in the face of the RM insult. This
      hepatoprotection appears to involve the rapid degradation of heme by heme
      oxygenase, with subsequent alterations in hepatic microvascular resistance and
      heme accumulation. The evidence from this investigation suggests that RM mediates
      a detrimental response in the hepatic parenchyma and microcirculation, and that
      these responses can be mediated by the rapid degradation of hepatic heme via CoPP
      induced heme oxygenase activity.

PMID- 15718929
TI  - Prophylactic high-dose N(omega)-monomethyl-L-arginine prevents the late cardiac
      dysfunction associated with lethal tumor necrosis factor-alpha challenge in dogs.
AB  - We investigated nitric oxide (NO) as a possible cause of the cardiac dysfunction
      associated with high, lethal doses of tumor necrosis factor-alpha (TNF-alpha) in
      dogs. Eighty-seven awake, 2-year-old (10-12 kg), purpose-bred beagles were
      randomized to receive an infusion of saline or N-monomethyl-L-arginine (L-NMMA),
      a nonselective NO synthase (NOS) inhibitor, as a 40 mg kg bolus followed by a 40
      mg kg(-1) h(-1) infusion for 3 to 6 h 3 h before (prophylactic) or 3 h after
      (therapeutic) challenge with TNF-alpha (60 microg kg(-1)) or vehicle. Serial
      radionuclide-heart scans and thermodilution pulmonary artery catheter hemodynamic
      measurements were performed. The effects of prophylactic L-NMMA on TNF-alpha
      induced cardiac dysfunction as measured by decreases in mean left ventricular
      (LV) ejection fraction and downward and rightward shifts of LV function plots
      (peak systolic pressure versus end systolic volume index and LV stroke work index
      versus end diastolic volume index) were significantly different comparing early
      (3-6 h) and delayed (24 h) time points (P = 0.02). Prophylactic L-NMMA therapy
      did not appear to fully prevent early (3-6 h) TNF-alpha-induced cardiac
      dysfunction, but at 24 h, complete protection was seen. Therapeutic L-NMMA did
      not appear to fully protect the heart from TNF-alpha-induced early or delayed
      cardiac dysfunction (P = NS). Similarly, L-NMMA given prophylactically, but not
      therapeutically, blocked TNF-alpha-induced increases in exhaled NO flow rates and
      plasma nitrite and nitrate concentrations (both P = 0.02). These data suggest
      that TNF-alpha initiates two phases of cardiac injury: an early (3-6 h) phase
      that may be partially NO independent and a delayed (24 h) phase that is NO
      dependent. The delayed, more persistent dysfunction can be completely blocked by
      high doses of a nonselective NOS inhibitor administered before TNF-alpha.

PMID- 15718934
TI  - Transcultural nursing theory from a critical cultural perspective.
AB  - This critical cultural discourse analysis explores the internal logic of
      Transcultural Nursing Theory and interrogates the underlying assumptions, goals,
      and strategies of this approach to race and other human and social differences.
      Drawing on examples from nursing textbooks and policy documents, I assert that
      Transcultural Nursing Theory operates from a liberal standpoint that focuses
      attention on a broadly defined, but narrowly applied, concept of culture. The
      goal of providing culturally competent care and the processes used to achieve
      that outcome reinforce, rather than transform, the social practices and relations
      that institutionalize the dominant approach to social and human differences.

PMID- 15718935
TI  - Toward a North-South dialogue: revisiting nursing theory (from the South).
AB  - In nursing, the current world situation calls us to revisit our knowledge schemes
      and revise the extent to which they assist us in improving the health of the
      world peoples. In this discussion, I offer a Latin American nursing perspective
      to knowledge development in our discipline. I suggest that a persistent concern
      to develop elaborate conceptualizations has distracted our attention from the
      realities practicing nurses face throughout the world. In their abstractness,
      (North) American nursing theories have conveyed a view that presumingly universal
      imposes itself as hegemonic in the international nursing community. Yet the
      exportation of these theories to other countries introduces a view that is
      foreign to practicing nurses. The world situation as well as the disparate and
      concurrent human paths that we witness and experience calls for approaches that
      are more in tune with the local realities of nursing practices.

PMID- 15718936
TI  - Health as a socially mediated process: theoretical and practice imperatives
      emerging from research on health inequalities.
AB  - Population-based studies on health disparities provide compelling evidence that
      inequities in health status over the life course accrue from social conditions.
      Our knowledge of how such conditions exert their effect on health, however, is
      limited. An examination of explanations for health disparities shows that a
      theoretical perspective that enables the exploration of the links between broader
      social processes (macro) and experience (micro) would offer valuable insights for
      practice. This article introduces a theoretical perspective informed by Bourdieu
      and Smith that has been used to undertake such an analysis and that opens up
      possibilities for new practice forums and foci.

PMID- 15718937
TI  - Advancing nursing theory through theory-guided practice: the emergence of a
      critical caring perspective.
AB  - Critical caring is proposed as a hybrid, midrange theory that builds on nursing
      science and critical feminist theories. As such, it has the potential to root
      public health nursing practice in an expanded nursing caring science that
      reincorporates the social justice agenda characteristic of early public health
      nursing practice but not featured prominently in contemporary nursing theories.
      Critical caring transforms the carative processes of Watson's theory into 7
      carative health-promoting processes that form the "core" of public health nursing
      practice and reflect the legacy and reality of public health nursing practice.

PMID- 15718938
TI  - Linking nursing theory and practice: a critical-feminist approach.
AB  - Situated in a critical-feminist perspective, this article describes a pedagogical
      approach to linking nursing theory and practice. The inclusion of the critical
      humanities is emphasized in creating an environment in which this linkage can be
      reified for learners. Implications for the future of nursing theory and its links
      to practice in the context of current political realities in academia are
      considered.

PMID- 15718939
TI  - A theoretical model of the determinants of mortality.
AB  - Outcome research in nursing has been criticized for being atheoretical. Although
      there has been research investigating patient mortality as an outcome, there has
      been little discussion about models or theories of nursing-related determinants
      of mortality for hospitalized patients. Yet, unnecessary patient mortality is an
      important patient safety outcome. This article describes development of beginning
      theory of determinants of patient mortality culminating with a revised mortality
      model. Conclusions are made related to plans for further testing and refinement
      of the revised mortality model. Further, the utility of the proposed model in
      practice is discussed.

PMID- 15718940
TI  - Understanding abuse of women with physical disabilities: an overview of the abuse
      pathways model.
AB  - The purpose of this article is to provide an overview of an empirically based
      theoretical model of abuse of women with physical disabilities. The Abuse
      Pathways model was developed from a critical disability life history research
      study conducted with 37 women who had simultaneously experienced abuse and
      physical disability. The model begins to address the complexity of abuse of women
      with physical disabilities by identifying the interactive components of the
      phenomenon. These components include (1) the social context of disability; (2)
      women's abuse trajectories; and (3) vulnerability factors for abuse. The article
      concludes by discussing potential applications and limitations of the model.

PMID- 15718941
TI  - Toward compassionate action: pragmatism and the inseparability of
      theory/practice.
AB  - Believing that the purpose of knowledge development and practice is compassionate
      action, in this article, we discuss how pragmatism can help us move toward that
      goal. Specifically, we show how pragmatic inquiry draws attention to the
      inseparability of practice/theory and the integral role practice experiences play
      in the ongoing development of theory. We demonstrate the utility of pragmatism to
      nursing by describing how we have explicitly approached theory development as a
      practical (and practice) activity of inquiry to attend to experiences of culture
      and diversity in family nursing.

PMID- 15718948
TI  - Advanced practice registered nurse update: issues of evolving complexity ... stay
      informed.

PMID- 15718949
TI  - Keeping up journal integrity: the peer-review process.

PMID- 15718952
TI  - Preparing a successful grant proposal--part 1: developing research aims and the
      significance of the project.

PMID- 15718951
TI  - Counseling patients undergoing urinary diversion: does the type of diversion
      influence quality of life?

PMID- 15718953
TI  - Development of a risk assessment tool for intraoperative pressure ulcers.
AB  - This article discusses the current literature related to intraoperative and
      preoperative risk factors for pressure ulcer development. Although surgical
      patients have a high risk of pressure ulcer development, the intraoperative
      period of patient care has often been missed as a time of increased risk.
      Pressure ulcers, which may originate in the operating room, may be incorrectly
      blamed on postoperative areas of care resulting from delay of pressure ulcer
      demarcation. In the literature review, current risk assessment tools do not
      adequately address intraoperative risk factors. A risk assessment tool that
      incorporates the specific variables relevant to the preoperative and
      intraoperative environment is proposed based on existing literature. A pilot
      study of the tool was done testing for intrarater reliability.

PMID- 15718955
TI  - Descriptive study of peristomal complications.
AB  - OBJECTIVE: The objective of this study was to assess new ostomy patients for the
      presence of peristomal complications when they returned for their 2-month
      postoperative follow-up at a major university hospital. DESIGN: A prospective
      descriptive design was used. SETTING AND SUBJECTS: For 1 year, new ostomy
      patients were seen at a 540-bed university-based hospital. Subjects included 220
      patients with ostomies who underwent a fecal or urinary diversion at a university
      based hospital. INSTRUMENTS AND METHODS: For 12 months, each patient who returned
      for a 2-month follow-up visit was assessed by 1 of 3 WOC nurses for the presence
      or absence of peristomal complications using a tool developed by the
      investigators. The study was conducted from August 2001 to August 2002.
      Descriptive statistics were used to summarize the data. RESULTS: A total of 220
      new ostomy patients were examined, 35 of whom had peristomal complications for a
      frequency of 16%. Sixteen of the 35 patients had ileostomies, 10 patients had
      colostomies, and 9 patients had ileal conduits. Of the 35 patients with
      peristomal complications, 24 had irritant dermatitis, 7 had mechanical injury,
      and 3 had Candida infections. The WOC nurses determined the causes of the
      peristomal complications to be related to flush stomas, peristomal hernias,
      inappropriate opening in the skin barrier, and mechanical injury from the
      pouching systems. Nine of 35 patients had flush stomas; 5 patients developed
      peristomal hernias. For 7 patients, the skin barrier in the pouching system was
      larger than the stoma, allowing the effluent to contact the peristomal skin,
      resulting in denuded peristomal skin; and 7 patients had pressure areas on the
      peristomal skin and were wearing convex pouching systems. CONCLUSIONS: With more
      laparoscopic ostomy surgeries resulting in decreased hospital stays, there is
      less opportunity for the patient to learn pouching techniques and problem solving
      regarding peristomal complications. Patients require more education regarding
      peristomal issues and follow-up after discharge to ensure the maintenance of a
      secure pouching system. Decreased hospital stays and decreased reimbursement for
      outpatient and home health services will continue to be a challenge for the WOC
      nurse. There is also a need for universal definitions of complications and the
      need for continued studies examining the frequency of these complications, as
      well as the role of stoma site marking in reducing these complications.

PMID- 15718957
TI  - There's a will...but is there a way? Patient perspectives in healthcare research,
      development, and decision making.

PMID- 15718956
TI  - Breaking the cycle of stigmatization: managing the stigma of incontinence in
      social interactions.
AB  - Incontinence is a highly stigmatizing condition. This article explores the
      dynamics of stigmatization in interpersonal interactions from the perspective of
      both individuals who are stigmatized and individuals who are not stigmatized.
      When people who are stigmatized and nonstigmatized interact with each other, both
      experience threats to self-esteem, but for different reasons. Individuals who are
      stigmatized may experience self-esteem decrements because they feel that their
      group is devalued in the eyes of others. Those who are nonstigmatized may fear
      that their actions will be perceived as biased, thereby threatening their self
      image as an unprejudiced person. Individuals who are stigmatized and
      nonstigmatized act in ways that make their worst fears more than likely come
      true. Ways that nurses can facilitate ending this cycle with patients who are
      incontinent are discussed.

PMID- 15719001
TI  - The epidemiology of hepatitis C virus infection. An update for clinicians.
AB  - Since the advent of sensitive diagnostic blood tests for the detection of
      antibody to hepatitis C virus (HCV) in donors, there has been a large decline in
      the incidence of transfusion-related hepatitis. Globally, the infection has an
      estimated prevalence of 3%, with a prevailing 1% in Europe while varying
      geographically within a North-South gradient, ranging from around 0.5% in
      Northern countries to 2% in Mediterranean area. The incidence is very difficult
      to estimate accurately as many patients with acute HCV infection are asymptomatic
      and, thus, do not present for diagnosis. Data from the US report a fall in the
      annual occurrence of new cases per year from 230,000 in the late 1980s to
      approximately 35,000 in the 1990s. Therefore, a reduction in incident cases might
      eventually lead to lower prevalence of HCV infection. Although the incidence of
      viral infection may be decreasing, the prevalence of liver disease caused by HCV
      is on the rise. This is due to the significant lag, often 20 years or longer,
      between the onset of infection and clinical manifestation of liver disease. HCV
      can be transmitted by a variety of routes. It is most efficiently passed on by
      large or repeated percutaneous exposures such as through transfusions,
      transplantation from an infected donor or intravenous drug use. Transmission may
      also occur from contacts with infected subjects in the household, through
      perinatal and parenteral exposures in the health care setting. The risk of sexual
      transmission of HCV is low. Despite this knowledge, nearly half of infected
      patients do not have a history suggesting a parenteral route of acquisition.
      Since a prophylactic vaccine is hitherto not available, prevention becomes
      extremely important: identification of infected persons and of risk factors
      associated with acquiring HCV allow to develop strategies for preventing the
      spread of infection as well as its complications, and for planning appropriate
      care and support services.

PMID- 15718959
TI  - Management of infants with ulcerated hemangiomas.

PMID- 15719002
TI  - Laboratory approaches to the diagnosis of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is a major and growing health problem
      worldwide. Laboratory testing plays an important role in the response to the HCV
      epidemic. Serologic tests for antibody to HCV are useful for screening purposes.
      The mainstays of laboratory testing for HCV, however, are the molecular
      approaches. Qualitative molecular tests are useful for confirmation of positive
      screening tests. Quantitative molecular tests provide prognostic information
      regarding the likelihood of response to therapy, and allow the monitoring of
      treatment efficacy. Similarly, genotyping assays predict response to therapy, and
      allow rational decisions regarding duration of treatment. The combination of
      continually improving laboratory testing, together with new drugs targeting
      distinct molecular determinants that are either essential or important in the
      viral replication cycle, is likely to lead to dramatic improvements in the
      management of HCV disease.

PMID- 15719003
TI  - Hepatitis C virus infection. How does the host respond?
AB  - The interaction between the host and the hepatitis C virus (HCV) results either
      in elimination of the virus or establishment of chronic infection. The principal
      mechanisms defining the outcome of infection are complex and largely yet to be
      determined. The perceived lack of a robust immune response against viral
      replication in chronic infection may actually reflect a dangerous homeostasis
      reached as the virus and immune system co-exist over time. Perturbing this
      contemporaneous relationship by aiming to control HCV replication, or eradicate
      the virus, may instead bring about an undesired self-destructive immune response.
      Recent studies have provided us with a better understanding of the virus-host
      interactions and may help us unravel the immunologic components necessary for
      successful HCV clearance.

PMID- 15719004
TI  - Treatment of chronic hepatitis c.
AB  - Since the discovering of the hepatitis C virus in 1989, the treatment of
      hepatitis C has considerably improved. Initially, with interferon alpha used as a
      single drug, the sustained virological response rate was below 20%. Then, with
      the use of combination therapy of interferon a with ribavirin, the response rate
      increased to 41%. More recently, combination of pegylated interferons with
      ribavirin give a response rate of about 54-63%. The long-term follow-up studies
      showed that sustained virological response is generally associated with clinical
      and histological improvement. The indication of therapy is mainly based on the
      results of the liver biopsy which is the best way to assess the prognosis of the
      liver disease. Therefore, treatment is indicated in patients with moderate or
      severe necroinflammation or fibrosis. The tolerability of combination therapy is
      relatively poor with a frequent flu-like syndrome and an impaired quality of
      life. Factors associated with a poor response to treatment are essentially
      genotype 1 and high viral load. To further improve the efficacy of therapy,
      different new drugs are under investigation (amantadine, cytokines). These drugs
      may be candidates for new combinations. In addition, intensive research is
      currently done for the development of inhibitors of viral enzymes (helicase,
      protease or polymerase) and anti-sense oligonucleotides, ribozymes and
      therapeutic vaccine.

PMID- 15719005
TI  - Retreatment of chronic hepatitis C virus infection in patients who failed to
      achieve sustained virologic response.
AB  - The treatment of patients with chronic hepatitis C virus (HCV) has improved
      dramatically over the past several years. Despite this nearly half of all
      patients fail to achieve a sustained virologic response (SVR) following therapy.
      The decision to retreat a non-responder depends upon several factors which
      include data regarding the response to the previous course of therapy and the
      likelihood that a favorable response can be achieved with retreatment. These
      factors must be balanced against the risk for fibrosis progression and developing
      cirrhosis in each individual patient before a decision is made for embark upon
      retreament. The management of patients who have failed to achieve SVR is
      therefore one of the most complicated in the spectrum of treating chronic HCV.
      This manuscript will review the factors to consider when assessing such patients,
      the likelihood of achieving an SVR with current therapy and options for patients
      who continue to manifest non-response.

PMID- 15719006
TI  - Natural history of hepatitis C and outcomes following liver transplantation.
AB  - Chronic hepatitis C virus (HCV) infection is common and affects a significant
      proportion of the population. Chronic HCV-related cirrhosis is the most common
      indication for liver transplantation (LT) in Australia, the United States (US),
      and most European countries. Unfortunately, the post-transplant recurrence of HCV
      is almost a universal phenomenon with approximately 6% to 23% of transplant
      recipients progressing to cirrhosis at a median of 3 to 4 years post-LT with a
      cumulative probability of developing graft cirrhosis estimated to reach 30% at 5
      years. The 1-year and 3-year actuarial risk of decompensation has been estimated
      at 42% and 62%, respectively. Similarly, the rate of progression from hepatic
      decompensation to death is accelerated after LT with a 3-year survival rate of
      less than 10% in decompensated HCV liver recipients. Ten percent to 25% of the
      patients with recurrent disease will require re-transplantation within 5 years.
      Because of the increasing number of patients transplanted for chronic HCV
      infection and the complexity of factors affecting this population we will present
      an up-to-date review concerning LT in the setting of HCV infection and cirrhosis
      with the goal of outlining the natural history, recurrence of infection, risk
      factors associated with severity of recurrence, treatment strategies for
      recurrent HCV infection, role of re-transplantation, and de-novo hepatocellular
      carcinoma.

PMID- 15719007
TI  - Course and treatment of recurrent Hepatitis C after liver transplantation.
AB  - Hepatitis C virus (HCV) related liver cirrhosis is the most common indication for
      orthotopic liver transplantation (OLT) in most transplant centers. However,
      recurrence of hepatitis C-infection after OLT in HCV positive patients is almost
      universal. Severity of graft hepatitis increases during the long term follow-up
      and up to 30% of patients develop severe graft hepatitis and cirrhosis. This led
      to decreased patient and graft survival in HCV positive patients. A number of
      variables like genotype, donor age, rejection treatment, cytomegalo-virus disease
      and liver retransplantation for HCV recurrence have shown to be associated with
      early and severe graft hepatitis. Prophylactic or therapeutic regimens which
      alter the course of disease in HCV positive patients are not established yet, and
      with longer follow-up the prevalence of HCV-related graft failure is likely to
      increase. New immunosuppressive regimens and anti-viral treatment with ribavarin
      in combination with pegylated interferon a have to be investigated to reduce the
      complications of HCV recurrence in the future.

PMID- 15719008
TI  - Update on hepatitis C treatment in HIV-coinfected patients.
AB  - Hepatitis C virus (HCV) infection has emerged as the main cause of morbidity and
      mortality in human immunodeficiency virus (HIV)-infected individuals, since the
      introduction of antiretroviral therapy. Coinfection with both viruses may lead to
      end-stage liver disease (ESLD), including cirrhosis and hepatocellular carcinoma.
      HCV infection is altered by HIV presence, although the effect of HCV on HIV
      infection is still controversial. For this reason, HCV screening is recommended
      in all HIV-infected persons. The final goal of HCV treatment is to eradicate the
      virus or, in other words, to eliminate the infection, and this objective is
      especially important in HIV/HCV-coinfected patients, because they have more
      severe liver disease, achieve less frequently sustained virologic response on
      treatment, and have limited access to orthotopic liver transplantation with
      respect to HCV-monoinfected patients. Combination therapy with pegylated
      interferon-alpha (pegIFN) and ribavirin (RBV) has become the standard treatment
      for chronic HCV infection. However, when we compare coinfected with monoinfected
      patients, this regimen has decreased efficacy, and the rate of adverse effects is
      higher.

PMID- 15719009
TI  - Is a modest weight loss significant in the improvement of dyslipidemic patients
      lipid profile.
AB  - AIM: The aim of the present study was to evaluate serum lipid abnormalities and
      the relationship with various factors in overweight and obese patients and to
      assess lipid profile modifications subsequent to weight loss in a subgroup of
      patients. METHODS: A sample of 110 obese out-patients first and a subgroup of 34
      subjects afterwards, was selected at the Human Nutrition Research Centre of the
      University of Pavia for a retrospective analysis. The subjects recruited were all
      dyslipidemic, according to the American Clinical Guidelines for the assessment of
      cardiovascular risk. Differences in lipid profiles in subjects with different
      life habits were evaluated and in a subgroup of 34 subjects compared before and
      after a short-term moderate hypocaloric diet. RESULTS: Sample's mean age was
      46.8+/-12.6 with a mean body mass index (BMI) of 32.1+/-4.8 kg/m2 (no difference
      with gender). The correlation analyses showed that total cholesterol (TC)
      concentrations were highly correlated with age (p<0.001); no correlation was
      found between TC and BMI, waist hip ratio (WHR), % body fat (BF%). Triglycerides
      (TG) concentrations were not related to age or BMI, however there was a
      significant correlation between TG and WHR and with waist circumference (WC)
      (p<0.001). The 34 subjects selected to take part in a dietary regimen, without
      significant changes in life habits, lost 5.1% of their initial weight and
      presented a significant improvement (p<0.001) in lipid profile. CONCLUSIONS: The
      high correlation between lipid profile and anthropometric measurements implies
      further longitudinal evaluation of the validity of the anthropometric indexes in
      the dyslipidemic patient management. Indeed, the results suggest that modest
      weight loss is sufficient to obtain a significant improvement in fasting serum
      lipid profile of dyslipidemic overweight patients.

PMID- 15719010
TI  - Prevalence of antibodies against hepatitis C virus and hepatitis B coinfection in
      healthy population in Bulgaria. A seroepidemiological study.
AB  - AIM: Viral hepatitis C is often silent and is sometimes discovered only by
      routine serologic testing. We investigated healthy adults for seroprevalence of
      antibodies against hepatitis C virus (HCV), for markers of hepatitis B (HBV)
      coinfection and for risk factors of transmission blood borne viruses. METHODS: We
      performed a descriptive cross sectional study for the period 1999-2000. A
      caseload of 2,211 healthy randomly selected subjects (aged 10-69, both sexes)
      from a big Bulgarian city gave informed consent for participation and answered a
      standardized questionnaire. Serum samples were obtained and tested using ELISA
      method for anti-HCV antibodies, HBV markers (HBsAg, anti-HBc and anti-HBs
      antibodies), as well as for anti-HIV-1.2 antibodies. RESULTS: The overall anti
      HCV seroprevalence was 1.08%, which coincides with the data submitted to WHO for
      the general Bulgarian population, as well as with the average data for Europe.
      Higher anti-HCV seroprevalence was ascertained with increasing age except in
      adolescents, in whom the anti-HCV positivity was high. A great part of the
      subjects with anti-HCV antibodies -- 62.5% had serological evidence for exposure
      to HBV. Anti-HCV carriage was in positive correlation with the summarized data
      for previous morbidity (surgery, blood transfusion and past liver disease), as
      well as with detecting markers for hepatitis B. In the studied caseload 0.68% had
      markers of double HCV and HBV infection. Nobody was found as seropositive for HIV
      1.2. CONCLUSIONS: The results of our study suggest the need of more stringent
      measures for prevention and control of HCV infection, including screening focused
      on different groups of population, precise determination of risk factors for HCV
      transmission and offering of HBV vaccine to HCV positive individuals to reduce
      the high risk of double HCV and HBV infection.

PMID- 15719011
TI  - [Need for hospital admission in patients with ulcerative colitis during
      maintenance with azathioprine].
AB  - AIM: The aim of this study is to analyse the clinical course of ulcerative
      colitis during maintenance therapy with azathioprine, a drug which is still not
      proved to be able to modify the natural history of the disease. METHODS: A
      retrospective study is made of data regarding the frequency of hospital admission
      for patients with ulcerative colitis referring to a gastroenterological Day
      Hospital between 1991 and 2000. The disease history of these patients has been
      divided into 2 sections: one preceding and the other following an index-event,
      identified as the beginning of a maintenance regimen with azathioprine; this
      allowed to find possible differences in the clinical course after the index
      event. Patients were controls of themselves. RESULTS: Seventeen patients
      qualified for analysis. Remission from an acute severe attack of ulcerative
      colitis was reached by intravenous or oral cyclosporine for 14 of them and by
      prednisone for 3 of them. The maintenance treatment with azathioprine, which
      started in all but 1 patient (intention-to-treat), showed a reduction in the
      number of hospital admissions, decreasing from a mean of 2.12+/-0.69 in the
      preceding 4.2+/-4.3 years to a mean of 0.12+/-0.33 in the following 5.8+/-2.5
      years (p=0.000). CONCLUSIONS: Patients undergoing maintenance therapy with
      azathioprine showed face fewer relapses needing hospitalisation than those
      without azathioprine.

PMID- 15719012
TI  - [A rare case of ileal leiomyoma. Diagnostic usefulness of ultrasonography
      imaging].

PMID- 15719013
TI  - Bcl-2 enhances Ca(2+) signaling to support the intrinsic regenerative capacity of
      CNS axons.
AB  - At a certain point in development, axons in the mammalian CNS undergo a profound
      loss of intrinsic growth capacity, which leads to poor regeneration after injury.
      Overexpression of Bcl-2 prevents this loss, but the molecular basis of this
      effect remains unclear. Here, we report that Bcl-2 supports axonal growth by
      enhancing intracellular Ca(2+) signaling and activating cAMP response element
      binding protein (CREB) and extracellular-regulated kinase (Erk), which stimulate
      the regenerative response and neuritogenesis. Expression of Bcl-2 decreases
      endoplasmic reticulum (ER) Ca(2+) uptake and storage, and thereby leads to a
      larger intracellular Ca(2+) response induced by Ca(2+) influx or axotomy in Bcl-2
      expressing neurons than in control neurons. Bcl-x(L), an antiapoptotic member of
      the Bcl-2 family that does not affect ER Ca(2+) uptake, supports neuronal
      survival but cannot activate CREB and Erk or promote axon regeneration. These
      results suggest a novel role for ER Ca(2+) in the regulation of neuronal response
      to injury and define a dedicated signaling event through which Bcl-2 supports CNS
      regeneration.

PMID- 15719014
TI  - Expression of AMAP1, an ArfGAP, provides novel targets to inhibit breast cancer
      invasive activities.
AB  - Identification of the molecular machinery employed in cancer invasion, but not in
      normal adult cells, will greatly contribute to cancer therapeutics. Here we found
      that an ArfGAP, AMAP1/PAG2, is expressed at high levels in highly invasive breast
      cancer cells, but at very low levels in noninvasive breast cancer cells and
      normal mammary epithelial cells. siRNA-mediated silencing of AMAP1 effectively
      blocked the invasive activities. AMAP1 expression in human breast primary tumors
      also indicated its potential correlation with malignancy. Paxillin and cortactin
      have been shown to colocalize at invadopodia and play a pivotal role in breast
      cancer invasion. We found that AMAP1 is also localized at invadopodia, and acts
      to bridge paxillin and cortactin. This AMAP1-mediated trimeric protein complex
      was detected only in invasive cancer cells, and blocking this complex formation
      effectively inhibited their invasive activities in vitro and metastasis in mice.
      Our results indicate that AMAP1 is a component involved in invasive activities of
      different breast cancers, and provide new information regarding the possible
      therapeutic targets for prevention of breast cancer invasion and metastasis.

PMID- 15719015
TI  - Importin alpha transports CaMKIV to the nucleus without utilizing importin beta.
AB  - Ca(2+)/calmodulin-dependent protein kinase type IV (CaMKIV) plays an essential
      role in the transcriptional activation of cAMP response element-binding protein
      mediated signaling pathways. Although CaMKIV is localized predominantly in the
      nucleus, the molecular mechanism of the nuclear import of CaMKIV has not been
      elucidated. We report here that importin alpha is able to carry CaMKIV into the
      nucleus without the need for importin beta or any other soluble proteins in
      digitonin-permeabilized cells. An importin beta binding-deficient mutant
      (DeltaIBB) of importin alpha also carried CaMKIV into the nucleus, which strongly
      suggests that CaMKIV is transported in an importin beta-independent manner. While
      CaMKIV directly interacted with the C-terminal region of importin alpha, the
      CaMKIV/importin alpha complex did not form a ternary complex with importin beta,
      which explains the nonrequirement of importin beta for the nuclear transport of
      CaMKIV. The cytoplasmic microinjection of importin alpha-DeltaIBB enhanced the
      rate of nuclear translocation of CaMKIV in vivo. This is the first report to
      demonstrate definitely that mammalian importin alpha solely carries a cargo
      protein into the nucleus without utilizing the classical importin beta-dependent
      transport system.

PMID- 15719016
TI  - Mechanisms of photoprotection and nonphotochemical quenching in pea light
      harvesting complex at 2.5 A resolution.
AB  - The plant light-harvesting complex of photosystem II (LHC-II) collects and
      transmits solar energy for photosynthesis in chloroplast membranes and has
      essential roles in regulation of photosynthesis and in photoprotection. The 2.5 A
      structure of pea LHC-II determined by X-ray crystallography of stacked two
      dimensional crystals shows how membranes interact to form chloroplast grana, and
      reveals the mutual arrangement of 42 chlorophylls a and b, 12 carotenoids and six
      lipids in the LHC-II trimer. Spectral assignment of individual chlorophylls
      indicates the flow of energy in the complex and the mechanism of photoprotection
      in two close chlorophyll a-lutein pairs. We propose a simple mechanism for the
      xanthophyll-related, slow component of nonphotochemical quenching in LHC-II, by
      which excess energy is transferred to a zeaxanthin replacing violaxanthin in its
      binding site, and dissipated as heat. Our structure shows the complex in a
      quenched state, which may be relevant for the rapid, pH-induced component of
      nonphotochemical quenching.

PMID- 15719017
TI  - Crystal structure and DNA-binding analysis of RecO from Deinococcus radiodurans.
AB  - The RecFOR pathway has been shown to be essential for DNA repair through the
      process of homologous recombination in bacteria and, recently, to be important in
      the recovery of stalled replication forks following UV irradiation. RecO, along
      with RecR, RecF, RecQ and RecJ, is a principal actor in this fundamental DNA
      repair pathway. Here we present the three-dimensional structure of a member of
      the RecO family. The crystal structure of Deinococcus radiodurans RecO (drRecO)
      reveals possible binding sites for DNA and for the RecO-binding proteins within
      its three discrete structural regions: an N-terminal
      oligonucleotide/oligosaccharide-binding domain, a helical bundle and a zinc
      finger motif. Furthermore, drRecO was found to form a stable complex with RecR
      and to bind both single- and double-stranded DNA. Mutational analysis confirmed
      the existence of multiple DNA-binding sites within the protein.

PMID- 15719018
TI  - Structure of an XPF endonuclease with and without DNA suggests a model for
      substrate recognition.
AB  - The XPF/Mus81 structure-specific endonucleases cleave double-stranded DNA (dsDNA)
      within asymmetric branched DNA substrates and play an essential role in
      nucleotide excision repair, recombination and genome integrity. We report the
      structure of an archaeal XPF homodimer alone and bound to dsDNA. Superposition of
      these structures reveals a large domain movement upon binding DNA, indicating how
      the (HhH)(2) domain and the nuclease domain are coupled to allow the recognition
      of double-stranded/single-stranded DNA junctions. We identify two nonequivalent
      DNA-binding sites and propose a model in which XPF distorts the 3' flap substrate
      in order to engage both binding sites and promote strand cleavage. The model
      rationalises published biochemical data and implies a novel role for the ERCC1
      subunit of eukaryotic XPF complexes.

PMID- 15719019
TI  - Maintenance of structure and function of mitochondrial Hsp70 chaperones requires
      the chaperone Hep1.
AB  - Hsp70 chaperones mediate folding of proteins and prevent their misfolding and
      aggregation. We report here on a new kind of Hsp70 interacting protein in
      mitochondria, Hep1. Hep1 is a highly conserved protein present in virtually all
      eukaryotes. Deletion of HEP1 results in a severe growth defect. Cells lacking
      Hep1 are deficient in processes that need the function of mitochondrial Hsp70s,
      such as preprotein import and biogenesis of proteins containing FeS clusters. In
      the mitochondria of these cells, Hsp70s, Ssc1 and Ssq1 accumulate as insoluble
      aggregates. We show that it is the nucleotide-free form of mtHsp70 that has a
      high tendency to self-aggregate. This process is efficiently counteracted by
      Hep1. We conclude that Hep1 acts as a chaperone that is necessary and sufficient
      to prevent self-aggregation and to thereby maintain the function of the
      mitochondrial Hsp70 chaperones.

PMID- 15719020
TI  - A receptor domain controls the intracellular sorting of the ferrichrome
      transporter, ARN1.
AB  - The Saccharomyces cerevisiae transporter Arn1p takes up the ferric-siderophore
      ferrichrome, and extracellular ferrichrome dramatically influences the
      intracellular trafficking of Arn1p. In the absence of ferrichrome, Arn1p sorts
      directly to the endosomal compartment. At low concentrations of ferrichrome,
      Arn1p stably relocalizes to the plasma membrane, yet little to no uptake of
      ferrichrome occurs at these low concentrations. At higher concentrations of
      ferrichrome, Arn1p cycles between the plasma membrane and endosome. Arn1p
      contains two binding sites for ferrichrome: one site has an affinity similar to
      the K(T) for transport, but the second site has a much higher affinity. Here we
      report that this high-affinity binding site lies within a unique extracytosolic,
      carboxyl-terminal domain. Mutations within this domain lead to loss of
      ferrichrome binding and uptake activities and missorting of Arn1p, including a
      failure to relocalize to the plasma membrane in the presence of ferrichrome.
      Mutation of phenylalanine residues in the cytosolic tail of Arn1p also lead to
      missorting, but without defects in ferrichrome binding. We propose that the
      carboxyl terminus of Arn1p contains a receptor domain that controls the
      intracellular trafficking of the transporter.

PMID- 15719021
TI  - Histone H3 phosphorylation can promote TBP recruitment through distinct promoter
      specific mechanisms.
AB  - Histone phosphorylation influences transcription, chromosome condensation, DNA
      repair and apoptosis. Previously, we showed that histone H3 Ser10 phosphorylation
      (pSer10) by the yeast Snf1 kinase regulates INO1 gene activation in part via
      Gcn5/SAGA complex-mediated Lys14 acetylation (acLys14). How such chromatin
      modification patterns develop is largely unexplored. Here we examine the
      mechanisms surrounding pSer10 at INO1, and at GAL1, which herein is identified as
      a new regulatory target of Snf1/pSer10. Snf1 behaves as a classic coactivator in
      its recruitment by DNA-bound activators, and in its role in modifying histones
      and recruiting TATA-binding protein (TBP). However, one important difference in
      Snf1 function in vivo at these promoters is that SAGA recruitment at INO1
      requires histone phosphorylation via Snf1, whereas at GAL1, SAGA recruitment is
      independent of histone phosphorylation. In addition, the GAL1 activator
      physically interacts with both Snf1 and SAGA, whereas the INO1 activator
      interacts only with Snf1. Thus, at INO1, pSer10's role in recruiting SAGA may
      substitute for recruitment by DNA-bound activator. Our results emphasize that
      histone modifications share general functions between promoters, but also acquire
      distinct roles tailored for promoter-specific requirements.

PMID- 15719022
TI  - Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of
      anthrax edema factor.
AB  - Edema factor (EF), a key anthrax exotoxin, has an anthrax protective antigen
      binding domain (PABD) and a calmodulin (CaM)-activated adenylyl cyclase domain.
      Here, we report the crystal structures of CaM-bound EF, revealing the
      architecture of EF PABD. CaM has N- and C-terminal domains and each domain can
      bind two calcium ions. Calcium binding induces the conformational change of CaM
      from closed to open. Structures of the EF-CaM complex show how EF locks the N
      terminal domain of CaM into a closed conformation regardless of its calcium
      loading state. This represents a mechanism of how CaM effector alters the calcium
      affinity of CaM and uncouples the conformational change of CaM from calcium
      loading. Furthermore, structures of EF-CaM complexed with nucleotides show that
      EF uses two-metal-ion catalysis, a prevalent mechanism in DNA and RNA
      polymerases. A histidine (H351) further facilitates the catalysis of EF by
      activating a water to deprotonate 3'OH of ATP. Mammalian adenylyl cyclases share
      no structural similarity with EF and they also use two-metal-ion catalysis,
      suggesting the catalytic mechanism-driven convergent evolution of two
      structurally diverse adenylyl cyclases.

PMID- 15719024
TI  - MHC class I molecules and KIRs in human history, health and survival.
AB  - MHC class I molecules are ligands for the killer-cell immunoglobulin-like
      receptors (KIRs), which are expressed by natural killer cells and T cells. The
      interactions between these molecules contribute to both innate and adaptive
      immunity. KIRs and MHC class I molecules are encoded by unlinked polymorphic gene
      families that distinguish all but the most related individuals. Combinations of
      MHC class I and KIR variants influence resistance to infections, susceptibility
      to autoimmune diseases and complications of pregnancy, as well as outcome after
      haematopoietic stem-cell transplantation. Such correlations raise the possibility
      that interplay between KIR and MHC class I polymorphisms has facilitated human
      survival in the presence of epidemic infections and has influenced both
      reproduction and population growth.

PMID- 15719023
TI  - E47 phosphorylation by p38 MAPK promotes MyoD/E47 association and muscle-specific
      gene transcription.
AB  - Selective recognition of the E-box sequences on muscle gene promoters by
      heterodimers of myogenic basic helix-loop-helix (bHLH) transcription factors,
      such as MyoD, with the ubiquitous bHLH proteins E12 and E47 is a key event in
      skeletal myogenesis. However, homodimers of MyoD or E47 are unable of binding to
      and activating muscle chromatin targets, suggesting that formation of functional
      MyoD/E47 heterodimers is pivotal in controlling muscle transcription. Here we
      show that p38 MAPK, whose activity is essential for myogenesis, regulates
      MyoD/E47 heterodimerization. Phosphorylation of E47 at Ser140 by p38 induces
      MyoD/E47 association and activation of muscle-specific transcription, while the
      nonphosphorylatable E47 mutant Ser140Ala fails to heterodimerize with MyoD and
      displays impaired myogenic potential. Moreover, inhibition of p38 activity in
      myocytes precludes E47 phosphorylation at Ser140, which results in reduced
      MyoD/E47 heterodimerization and inefficient muscle differentiation, as a
      consequence of the impaired binding of the transcription factors to the E
      regulatory regions of muscle genes. These findings identify a novel pro-myogenic
      role of p38 in regulating the formation of functional MyoD/E47 heterodimers that
      are essential for myogenesis.

PMID- 15719025
TI  - The role of BH3-only proteins in the immune system.
AB  - Programmed cell death--also known as apoptosis--has a crucial role in the immune
      system of mammals and other animals. It removes useless cells and potentially
      dangerous cells, including lymphocytes, and is involved in killing pathogen
      infected or damaged cells. Defects in this process have been found to cause or
      contribute to diseases of the immune system, including immunodeficiency,
      autoimmunity, lymphoma and leukaemia. This review describes BH3-only proteins, a
      pro-apoptotic subgroup of the BCL-2 family, and their role in the development and
      function of the immune system.

PMID- 15719026
TI  - Mechanisms of apoptosis induction by the HIV-1 envelope.
AB  - The envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1)
      can induce apoptosis by a cornucopia of distinct mechanisms. A soluble Env
      derivative, gp120, can kill cells through signals that are transmitted by
      chemokine receptors such as CXCR4. Cell surface-bound Env (gp120/gp41), as
      present on the plasma membrane of HIV-1-infected cells, can kill uninfected
      bystander cells expressing CD4 and CXCR4 (or similar chemokine receptors,
      depending on the Env variant) by at least three different mechanisms. First, a
      transient interaction involving the exchange of lipids between the two
      interacting cells ('the kiss of death') may lead to the selective death of single
      CD4-expressing target cells. Second, fusion of the interacting cells may lead to
      the formation of syncytia which then succumb to apoptosis in a complex pathway
      involving the activation of several kinases (cyclin-dependent kinase-1, Cdk1;
      checkpoint kinase-2, Chk2; mammalian target of rapamycin, mTOR; p38 mitogen
      activated protein kinase, p38 MAPK; inhibitor of NF-kappaB kinase, IKK), as well
      as the activation of several transcription factors (NF-kappaB, p53), finally
      resulting in the activation of the mitochondrial pathway of apoptosis. Third, if
      the Env-expressing cell is at an early stage of imminent apoptosis, its fusion
      with a CD4-expressing target cell can precipitate the death of both cells,
      through a process that may be considered as contagious apoptosis and which does
      not involve Cdk1, mTOR, p38 nor p53, yet does involve mitochondria. Activation of
      some of the above- mentioned lethal signal transducers have been detected in
      patients' tissues, suggesting that HIV-1 may indeed trigger apoptosis through
      molecules whose implication in Env-induced killing has initially been discovered
      in vitro.

PMID- 15719027
TI  - Ruthenium red-mediated suppression of Bcl-2 loss and Ca(2+) release initiated by
      photodamage to the endoplasmic reticulum: scavenging of reactive oxygen species.
AB  - The photosensitizer 9-capronyloxytetrakis (methoxyethyl) porphycene localizes
      predominantly in the endoplasmic reticulum (ER) and, to a lesser extent, in
      mitochondria of murine leukemia L1210 cells. Subsequent irradiation results in
      the loss of ER > mitochondrial Bcl-2 and an apoptotic response. Although an
      increase in cytosolic Ca(2+) was observed after irradiation, apoptosis was not
      inhibited by either the presence of the calcium chelator BAPTA or by the
      mitochondrial uniporter inhibitor ruthenium amino binuclear complex (Ru360).
      Moreover, neither reagent prevented the loss of Bcl-2. Ruthenium red (RR) devoid
      of Ru360 prevented Bcl-2 loss, release of Ca(2+) from the ER and the initiation
      of apoptosis. Since RR was significantly more sensitive than Ru360 to oxidation
      by singlet oxygen, we attribute the protective effect of RR to the quenching of
      reactive oxygen species. Although cytosolic and (to a lesser extent)
      mitochondrial Ca(2+) levels were elevated after photodynamic therapy, these
      changes were apparently insufficient to contribute to the development of
      apoptosis.

PMID- 15719028
TI  - Cell death by the sea.

PMID- 15719029
TI  - RNAi technology and lentiviral delivery as a powerful tool to suppress Tpr-Met
      mediated tumorigenesis.
AB  - Tpr-Met, the oncogenic counterpart of the Met receptor, has been detected in
      gastric cancers, as well as in precursor lesions and in the adjacent normal
      gastric mucosa. This has prompted the suggestion that Tpr-Met may predispose to
      the development of gastric tumors. Given the sequence specificity of RNA
      interference, oncogenes activated by point mutation or rearrangements can be
      targeted while spearing the product of the wild-type allele. In this work, we
      report specific suppression of Tpr-Met expression and inhibition of Tpr-Met
      mediated transformation and tumorigenesis by means of a short interfering RNA
      (siRNA) directed toward the Tpr-Met junction (anti-TM2). When delivered by a
      lentiviral vector, anti-TM2 siRNA was effective also in mouse embryonal
      fibroblasts or epithelial cells expressing high levels of Tpr-Met. Our results
      suggest that lentiviral-mediated delivery of anti-TM2 siRNA may be developed into
      a powerful tool to treat Tpr-Met-positive cancers.

PMID- 15719030
TI  - Detection and interpretation of altered methylation patterns in cancer cells.
AB  - Epigenetic alterations, such as abnormal DNA-methylation patterns, are associated
      with many human tumour types. New techniques have been developed to perform
      genome-wide screening for alterations in DNA-methylation patterns, not only to
      identify tumour-suppressor genes, but also to find patterns that can be used in
      diagnosis and prognosis. However, interpretation of differential methylation has
      proven difficult because the significance of methylation alterations depends on
      the genomic region, and functions of CpG islands at specific sites have not been
      fully clarified. What techniques can be used to identify new tumour suppressors
      and diagnostic markers?

PMID- 15719031
TI  - Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia.
AB  - Imatinib, a potent inhibitor of the oncogenic tyrosine kinase BCR-ABL, has shown
      remarkable clinical activity in patients with chronic myelogenous leukaemia
      (CML). However, this drug does not completely eradicate BCR-ABL-expressing cells
      from the body, and resistance to imatinib emerges. Although BCR-ABL remains an
      attractive therapeutic target, it is important to identify other components
      involved in CML pathogenesis to overcome this resistance. What have clinical
      trials of imatinib and studies using mouse models for BCR-ABL leukaemogenesis
      taught us about the functions of BCR-ABL beyond its kinase activity, and how
      these functions contribute to CML pathogenesis?

PMID- 15719032
TI  - Lysosomal cystine augments apoptosis and causes the phenotype in cystinosis.
AB  - Nephropathic cystinosis is a lethal inborn error of metabolism that destroys
      kidney function by age 10 years. It is characterized by lysosomal cystine
      accumulation. How the cystine causes the phenotype is an open question. We
      propose that during apoptosis, permeablized lysosomes permit cystine to reach the
      cytosol where mixed disulfide formation occurs, augmenting apoptosis by
      interaction with a variety of pro-apoptotic proteins.

PMID- 15719033
TI  - Clinical cytogenetic diagnosis of therapy-related acute myeloid leukemia.
AB  - Therapy-related acute myeloid leukemia (tAML) is one of the two forms of
      secondary acute myeloid leukemia, with one derived from de novo myelodysplastic
      syndrome (MDS) and the other from exposure to environmental or therapeutic agents
      such as radiation and toxins. There has been a marked increase in the number of
      incidences of therapy-related acute myeloid leukemia. It has become a distinctive
      disease because of its etiology and genetic tumorigenesis. The majority of tAML
      resulting from the use of cytotoxic agents can be divided into two groups based
      on the drugs administered to the patient. The first group includes the use of
      alkylating agents, and the second group includes agents that bind to the enzyme
      DNA-topoisomerase II. Due to the unfavorable outcome of the disease and the need
      for prompt intensive treatment, a timely accurate diagnosis of tAML is critical
      to patient care. Cytogenetic study can detect abnormalities most commonly
      associated with tAML and thus providing important diagnostic information.
      However, utilizing cytogenetic analysis alone cannot guarantee prompt and
      accurate results. In this study, an interesting case with therapy-related
      myelodysplastic syndrome and acute myeloid leukemia (tMDS/tAML) will be
      presented. A laboratory diagnostic strategy for tAML laboratory diagnosis will
      also be proposed.

PMID- 15719034
TI  - Advanced molecular and cytogenetic technologies in birth defect diagnosis and
      prevention.
AB  - Fluorescence in situ hybridization (FISH) has become an important diagnostic tool
      as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of
      specific nucleic acid sequences tagged with fluorescent molecules to identify the
      number and location of specific DNA sequences in human cells. These probes can be
      used to determine various numerical and structural chromosomal aberrations, in
      many cases, gene dosage and/or structure alterations. Chromosomal abnormalities
      are responsible for a considerable number of birth defects, and more than 50% of
      spontaneous abortions. These numbers have been significantly higher since the
      advent of FISH technology that allows the detection of submicroscopic chromosome
      alterations. The clinic application of FISH technology in postnatal, prenatal,
      and preimplantation diagnoses has been playing an important role in the diagnosis
      and prevention of birth defects. As new technologies evolve, more and more new
      FISH techniques-such as subtelomeric FISH, multicolor FISH (M-FISH), comparative
      genomic hybridization (CGH), and microarray-are used in clinical diagnoses, the
      role of FISH technology in both research and clinical aspects of birth defects
      will surely continue to expand.

PMID- 15719036
TI  - Molecular genetics of common mitochondrial DNA disorders.
AB  - Diagnosis of mitochondrial disorders has been difficult due to the clinical and
      genetic heterogeneity, as well as unique features of mitochondrial genetics.
      Definitive diagnosis requires the identification of molecular defects in either
      the mitochondrial or the nuclear genome. We describe the clinical and molecular
      characteristic of some common mitochondrial syndromes and molecular methodologies
      available for the detection of mitochondrial DNA mutations. This review provides
      overview of current molecular diagnosis of mitochondrial DNA disorders that is
      useful in patient care and genetic counseling.

PMID- 15719035
TI  - Prenatal diagnostic testing for infantile and late-infantile neuronal ceroid
      lipofusinoses (NCL) using allele specific primer extension (ASPE).
AB  - Infantile (INCL, NCL1) and late-infantile (LINCL, NCL2) neuronal ceroid
      lipofuscinoses have been found to result from genetic deficiency of genes CLN(1 )
      and CLN(2), respectively. The application of molecular analyses can facilitate
      prenatal diagnosis for families affected by NCL1 or NCL2, in which the familial
      mutation(s) have been identified. Molecular testing with allele-specific primer
      extension and DNA sequencing was performed in nine pregnancies, four from two
      NCL1 families and five from five NCL2 families. Lysosomal enzyme activity assays
      were carried out as well.Four fetuses from three pregnancies in NCL1 families
      were found to be carriers for a mutation 451C-T in the CLN(1) gene and one was
      normal. Prenatal testing of three NCL2 families who carried mutation R208X in the
      CLN(2) gene showed that all fetuses were carriers. In NCL2 families who carried
      either mutation IVS5-1C or/and IVS5-1A two normal pregnancies were detected. Our
      studies indicate that DNA testing, which may provide definitive prenatal
      diagnosis for NCL, may be used in combination with lysosomal enzyme activity
      analyses.

PMID- 15719037
TI  - Disorders of sexual development caused by luteinizing hormone receptor mutations.
AB  - The Luteinizing hormone/chorionic gonadotropin receptor (LHR) plays a critical
      role in human male sexual development. Both gain-of-function and loss-of-function
      mutations of the LHR have been described. Gain-of-function mutations are dominant
      and cause constitutive activation of the receptor resulting in familial male
      limited precocious puberty (FMPP). All activating mutations are single point
      mutations and are located in the transmembrane domain (TM). TM helix VI harbors
      the largest number of activating mutations with the codon of Asp-578 being the
      hot-spot of mutation. Besides causing abnormal sexual development, constitutively
      activated LHR may predispose an individual to the development of testicular
      neoplasia. The anti-thesis of FMPP is Leydig cell hypoplasia (LCH). This is
      caused by mutations that inactivate the LHR resulting in subnormal male sexual
      development or male pseudohermaphroditism. Inactivating mutations are recessive.
      The genetic cause of LCH is variable and there is no mutation hot-spot. Genotype
      phenotype correlation can be identified in LCH with the milder form caused by
      mutated LHR with residual activity and the severe form caused by absence of
      signal transduction activity of the mutated receptor. Molecular diagnosis of the
      disorders caused by mutation of the LHR can be achieved by direct sequencing of
      the LHR gene.

PMID- 15719038
TI  - [Screening for chromosomal abnormalities using nuchal translucency measurement
      with materal serum biochemistry markers in first trimester].
AB  - OBJECTIVE: To Investigate the performance of prenatal screening for chromosomal
      abnormalities in first trimester. METHODS: Maternal serum were collected from 2
      739 pregnant women between 11 and 14 weeks gestation. Free beta human chorionic
      gonadotrophin(beta-hCG), pregnancy-associated plasma protein(PAPP-A) from materal
      serum were measured using time resolved fluorescence immunoassay(TRFIA) and fetal
      nuchal translucency(NT) thickness were measured using transabdominal or
      transvaginal ultrasound. 22 chromosomal defects were diagnosed in 22 cases using
      karyotyping. The levels of three markers were analyzed among 22 cases and 870
      controls. RESULTS: The level of three markers were significant difference between
      affected and unaffected pregnancies. In affected cases, the value or level of NT
      and free beta-hCG were higher, while the level of PAPP-A was lower. We found that
      screening for chromosomal defects using a combination of NT and serum
      biochemistry was associated with a detection rate of 91.67% for all types of
      chromosomal defects, with a false-positive rate of 11.16%. CONCLUSION: A
      combination of nuchal translucency measurement with materal serum biochemistry
      markers provides an effective method of screening for chromosomal defects.

PMID- 15719039
TI  - [Screening for congenital hypothyroidism in 106 224 neonates in Hunan Province].
AB  - OBJECTIVE: Diagnosing congenital hypothyroidism (CH) early was studied in this
      paper through neonatal screening to prevent children's mental retardation.
      METHODS: The first step is mensurating the concentration of thyroid stimulating
      hormone (TSH) with the method of time-distinguished fluorometry immunoassay. If
      the result is positive, then it is necessary to mensurate the serum TSH, free
      triiodothyronine (FT3),free thyroxin (FT4) with chemiluminescence immunoassay
      (CLIA) and execute clinical diagnosis. RESULTS: There were 68 confirmed
      congenital hypothyroidism patients among the 106,224 samples from Apr.1997 to
      Dec.2003 in Hunan province. The positive rate was 1/1,562, which was obviously
      higher than the national average value (1/3,009). CONCLUSION: First, neonatal
      screening is the key to prevent mental retardation through early diagnosing and
      treating CH. Second, the probability of suffering CH is high in Hunan province.
      Third, the positive rate is relative to the development of science and
      technology, while the accumulated rate is better to reflect the real incidence of
      the disease. Fourth, selecting proper critical value will help to prevent missing
      screening.

PMID- 15719040
TI  - [The establishment and clinical application of multicolor fluorescence in situ
      hybridization].
AB  - OBJECTIVE: To establish a rapid and convenient method of multi-color fluorescence
      in situ hybridization (FISH) on several different tissue samples: peripheral
      blood samples, amniotic fluid, embryos and bone marrow samples. METHODS: FISH
      analysis was carried out on different tissue samples, using probes specific for
      chromosomes 13,18,21,X and Y or for BCR/ABL gene. RESULTS: FISH analysis could
      reveal hybridization signals on metaphase chromosomes and interphase nuclei, it
      is also possible to detect chromosome aberrations. CONCLUSION: Multi-color FISH
      is clinically useful tool, which can be used as an adjunct to conventional
      chromosome analysis for prenatal diagnosis , preimplantation genetic diagnosis
      and diagnosis of leukemia.

PMID- 15719041
TI  - [PAX6 mutation caused brain abnormalities in humans].
AB  - OBJECTIVE: To investigate the association between PAX6 mutation and brain
      abnormalities. METHODS: The brain structures of 18 affected patients and 6 normal
      controls in a large pedigree with a PAX6 mutation (c1080C-->T)were scanned with
      MRI assessing. RESULTS: Most of the affected patients showed brain abnormalities
      such as corpus callosum degeneration, broad cerebral ventricle grooves and broad
      olfactory grooves. CONCLUSION: Genetic defect of PAX6 gene may result in brain
      abnormalities.

PMID- 15719043
TI  - Detection of homozygous and heterozygous SMN deletions of spinal muscular atrophy
      in a single assay with multiplex ligation-dependent probe amplification.
AB  - OBJECTIVE: Spinal muscular atrophy(SMA), an autosomal recessive neuromuscular
      degeneration of the anterior horn cells of the spinal cord and brain stem,
      results in one of the most common diseases with muscle fatigue and atrophy. Most
      SMA cases including all the types are due to the homozygous deletion of at least
      exon 7 within the survival motor neuron 1 (SMN-1) gene. Although a "golden
      standard" assay (PCR with mismatch primer followed by enzyme digestion) is very
      reliable for the identification of homozygous SMN-1 deletion, the carrier
      detection of heterozygous SMN-1 deletion remains a challenge. METHODS: Some PCR
      based gene dosage assays or multiplex PCR allow for the determination of the copy
      number of SMN-1 gene to identify heterozygous deletion, but these procedures are
      often time consuming and available on a limited clinical basis. Recently
      developed MLPA (multiplex ligation-dependent probe amplification) is an efficient
      procedure that can accurately analyze relative quantification to establish the
      copy number of the SMN gene. We performed a validation for simultaneous detection
      of homozygous SMN-1 deletions of SMA patients and heterozygous SMN-1 deletions of
      SMA carriers in a simple assay using a MLPA-SMA assay specific reagent. RESULTS:
      Six out of 20 patients with SMA were found to have homozygous SMN-1 deletion,
      confirmed by the PCR/digestion assay. All 4 parents of the children with SMA had
      heterozygous SMN-1 deletion, confirmed by an independent relative quantitative
      analysis. CONCLUSION: MLPA provides a simple, rapid and accurate method of
      simultaneously detecting homozygous deletions and heterozygous deletions in a
      single assay for both SMN-1 and SMN-2 genes.

PMID- 15719042
TI  - Development of a molecular screening test for hereditary hearing loss and genetic
      susceptibility to aminoglycoside toxicity for Chinese population.
AB  - OBJECTIVE: To develop a molecular screening test for genetic defects on hearing
      loss related genes has significant impacts on early identification of hereditary
      hearing loss and genetic susceptibility to aminoglycoside ototoxicity. Early
      identification of pre-lingual hearing loss is very important for patient' s
      language development, academic achievement, and social skill. Two common
      mutations, the 235delC in GJB2 gene and the mutation A1555G in mitochondrial DNA,
      are included in the newly developed screening panel for Chinese population.
      METHODS: A molecular genetic assay, based on fluorescent labeled multiplex PCR
      and automatic DNA fragment analyzing techniques, was developed to detect both
      mutations simultaneously. RESULTS: This assay was able to detect both mutations
      from patient's samples, and pooled DNA tests, as well as suitable to detect
      mutation from the DNA extracted from dried blood spot and buccal swab.
      CONCLUSION: This assay could be a useful tool for newborn screening and carrier
      screening for the hereditary hearing loss for the Chinese population.

PMID- 15719044
TI  - [Preliminary exploration of the influence factors on amplification of single cell
      duplex-nested PCR].
AB  - OBJECTIVE: To explore the influence factors on amplification of single cell
      duplex-nested PCR. METHODS: The mutational loci region CD41-42 and IVS-II 654 of
      beta-globin gene were amplified by duplex-nested PCR with different combination
      of primers concentration, different Taq DNA polymerases, different neutralization
      buffers and with or without predenaturation at 98 degrees C before the PCR
      amplification in single lymphocyte or single blastomere, thus, to investigate the
      influence of these factors on the amplification efficiency of PCR. RESULTS:
      TaKaRa EX Taq was the most efficient Taq DNA polymerase among different Taq DNA
      polymerases; primer pair R1+F1 at final concentration of 0.25 micromol/L and
      R2+F2 at 0.3 micromol/L were the most efficient ones in amplification among
      different combinations of primers concentrations; the amplification efficiency in
      neutralization buffer-1 (200 mmol/L Tricine) was obviously higher than that of
      neutralization buffer-2 (900 mmol/L Tris-HCl, pH 8.3/300 mmol/L KCl/200 mmol/L
      HCl)(P<0.05); there were no remarkable differences of the amplification
      efficiency while using whether predenaturation at 98 degrees C before the single
      cell PCR amplification or not (P>0.05). CONCLUSION: There were remarkable
      differences of the amplification efficiency of single cell duplex-nested PCR
      while using different combination of primers concentrations, different Taq DNA
      polymerases, different neutralization buffers. However, predenaturation at 98
      degrees C before the single cell PCR amplification could not improve the PCR
      amplification efficiency.

PMID- 15719046
TI  - Mutation screening of Cx32 in Han Chinese patients with Charcot-Marie-Tooth
      disease.
AB  - OBJECTIVE: To investigate the Cx32 mutation features and the clinical
      manifestations of Chinese patients with Charcot-Marie-Tooth disease(CMT).
      METHODS: Twenty-four of 65 unrelated CMT patients were selected for Cx32 mutation
      screening after the exclusion of the CMT1A 1.5 Mb duplication and male-to-male
      transmission. The motor and sensory nerve conduction studies were performed in
      all probands and most of their affected family members to establish the clinical
      CMT1 ,CMT2 or CMT intermediate diagnosis. The presence of mutations in the coding
      region of Cx32 was detected by single-strand conformation polymorphism analysis
      combined with direct sequencing. RESULTS: We found 7 different point mutations in
      the coding region of Cx32 in a total of 7 families. All the patients were mildly
      to moderately affected with a clinical CMT1 or CMT intermediate diagnosis. The
      mutation Arg15Gln was inherited with X-linked recessive trait in family 1
      involved in our study. The Arg75Trp mutation was detected in a family with X
      linked dominant CMT and autosomal recessive nonsydromic hearing loss. The
      clinical phenotype of the Thr188Ala mutation was firstly reported. CONCLUSION:
      Seven different Cx32 point mutations were detected and the percentage of Chinese
      CMT families with Cx32 mutation is about 10% in our study. The inheritance model
      of CMT secondary to Cx32 mutation could be X-linked dominant, X-linked recessive
      or sporadic. Male patients are usually more severely affected than females with
      slower nerve conduction velocities. Cx32 mutation screening should be firstly
      performed in those CMT families without male-to-male transmission and CMT1A
      duplication.

PMID- 15719045
TI  - Effectiveness of multiplex ligation-dependent probe amplification assay used for
      detecting deletion of Prader-Willi syndrome.
AB  - OBJECTIVE: Prader-Willi syndrome (PWS) is characterized by severe hypotonia and
      feeding difficulties in early infancy, followed by excessive eating and gradual
      development of morbid obesity in later infancy or early childhood. Patients with
      PWS are often too young to manifest sufficient features or have atypical
      findings, making genetic testing important to confirm the diagnosis of PWS.
      Approximately 99% of patients with PWS have a diagnostic abnormality in the
      parent-specific methylation imprint within the Prader-Willi critical region
      (PWCR) at chromosome 15q11.2-q12. Of them, 70% have a paternal deletion; 25% have
      a maternal uniparental disomy (UPD); and <5% have a mutation in the imprinting
      center. METHODS: Current techniques can identify a diagnostic abnormality, such
      as paternal deletion or maternal UPD for most of patients with PWS, but they are
      labor-intensive and cost-expensive. Multiplex ligation-dependent probe
      amplification (MLPA) is a novel, simple, and cost-effective technique for
      analysis of relative quantification in a single assay, which has recently been
      applied for the detection of genomic deletions, duplications, and amplifications
      in a variety of genes. RESULTS: Six out of 20 patients referred for genetic
      diagnosis of PWS were found to have a deletion by MLPA, confirmed by FISH and DNA
      methylation analysis with 100% concordance. CONCLUSION: MLPA's high sensitivity
      and specificity for deletion detection is the same as FISH or Southern blot based
      analysis. Additional collaborative effort for developing and validating the
      complete MLPA-PWS assay, for not only detecting deletion but also identifying
      methylation abnormality, is on going.

PMID- 15719047
TI  - [Screening for the G1528C mutation in long chain fatty acid oxidation enzyme in
      Han nationality in Beijing population].
AB  - OBJECTIVE: To explore the carrier rate of G1528C mutation in alpha-subunit gene
      of MTP in Chinese newborns. METHODS: 1 200 cases of cord blood samples were taken
      in pregnant women with Han nationality in Chinese. PCR-RFLP analysis was
      conducted for detection of G1528C mutation. RESULTS: No. G1528C mutations in
      LCHAD gene were found in these study subjects. CONCLUSION: G1528C is probably not
      the common prevalent mutation in MTP gene in Chinese. Different prevalent
      mutation between Chinese and Western white people needs further study.

PMID- 15719048
TI  - [Study of serum Hcy and polymorphisms of Hcy metabolic enzymes in 192 families
      affected by congenital heart disease].
AB  - OBJECTIVE: To explore genotype distributions at MTHFR C677T, MS A2756G, MTHFD
      G1958A and CBS 844 ins68bp loci in healthy Chinese living in northern area, and
      to assess the association of single or combined gene mutations with folic acid,
      Vit.B(12), Hcy levels and CHD. METHODS: 192 patients having CHD and their
      biological parents in Liaoning province registered as birth defects were included
      in this study as case group, and 124 healthy subjects (age and gender matched)
      and their biological parents were simultaneously selected from the same
      geographic area as control. To all subjects, the gene polymorphism at MTHFR
      C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci was examined with PCR
      RFLP. The serum folic acid and homocysteine (Hcy) level were analyzed with
      Radioimmunoassay or fluorescence polarization immunoassay (FPIA). RESULTS: In
      healthy Chinese living in northern China, the mutant allele frequencies of these
      four loci were MTHFR 51.18%, MS 7.58%, MTHFD 24.32%, and CBS insertion 2.36%,
      respectively. The heterozygosity of CBS 844 ins68bp was more prevalent in case
      than in control (12.57% vs 2.97% in children, 10.88% vs 3.09% in father and
      11.54% vs 1.02% in mother, respectively), and yielded an odds ratio (OR) of 4.70
      (95% CI 1.34-25.15) in children, 3.83 (95% CI 1.05-20.98) in fathers and 12.65
      (95% CI 1.92-532.47) in mothers. There is no existed significant difference at
      the other three loci. The percents of mothers with MTHFR, CBS and MTHFD gene
      polymorphisms, of mothers with MTHFR and CBS being polymorphisms (OR=8.44, 95aCI
      1.23-362.26), of mothers with MTHFD and CBS being polymorphisms in case were
      higher than those in control. Serum folic acid levels of mothers and fathers in
      case were significantly higher than those of counterparts in control. Serum Hcy
      level of mothers in case was higher than that of counterparts in control without
      significant difference. Homozygous mutation at MTHFR and MTHFD loci made serum
      folic acid and Vit.B(12) levels slightly decreased and serum Hcy level increased.
      CONCLUSION: The study showed presence of ethnic and district difference of gene
      polymorphisms at these four loci. 68 bp insertion at exon 8 of CBS gene base 844
      could be a risk factor for CHD, and the insertion in parents (especially in
      mothers) could increase CHD risk in offspring.

PMID- 15719049
TI  - [The role of biomarkers CK7, Vim and P53 in the development of subtypes of
      endometrial carcinoma].
AB  - OBJECTIVE: Analyzing the protein expression of biomarkers CK7, Vim, and P53 to
      investigate their possible pathogenic roles in the development of variant
      subtypes of endometrial carcinoma. METHODS: Biomarkers CK7, Vim, and P53 were
      immunohistochemistry-stained among 131 endometrial carcinoma specimens including
      93 endometroid, 8 adenoacanthoma, and 32 rare subtypes of adenosquamas carcinoma,
      clean cell carcinoma, and papillary carcinoma, which had been confirmed
      clinically and pathologically, and studied statistically with Fisher test and
      Cochran-Mantel-Haenszel (CMH) Test. RESULTS: Positive correlation was
      demonstrated among CK7, Vim, and P53 expression levels. The CK7 protein
      expression is increased, while the Vim and P53 are decreased in the subtype of
      endometrioid carcinoma. The clinical staging of endometriroid carcinoma is
      positively correlated with the expression of Vim. The positive rate of Vim and
      P53 is correlated with cytological differentiation of the carcinoma cells.
      CONCLUSION: Biomarkers CK7, Vim, and P53 are playing pathogenic roles, assuming
      as a mutual transcriptional modulator, and Vim but not P53 is likely the
      favorable prognostic factor, in the development of variant subtypes of
      endometrial carcinoma in addition to a evaluating the treatment.

PMID- 15719050
TI  - [Associations of genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with
      low birth weight in neonates].
AB  - OBJECTIVE: To investigate whether genetic polymorphisms in the microsomal epoxide
      hydrolase gene (EPHX1) and the glutathione S-transferase theta1 gene (GSTT1) are
      associated with low birth weight in neonates. METHODS: Using standard
      questionnaires, 246 singleton live born mother-neonates pairs (73 cases were
      mother-low birth weight neonate pairs and 173 controls were mother-non low birth
      weight neonate pairs) were investigated by the trained field workers with case
      control study at the hospital in Anqing, Anhui Province, China between 1998 and
      1999. A total of 246 neonates were genotyped for genetic polymorphisms in the
      EPHX1 gene and the GSTT1 gene by a polymerase chain reaction-restriction fragment
      length polymorphism assay. Multiple linear regression models were used to
      estimate the association of the genetic polymorphisms in the EPHX1 gene and the
      GSTT1 gene with neonatal low birth weight, adjusting for maternal age, education,
      parity, neonatal sex and gestational age. RESULTS: EPHX1 His139His homozygote was
      not associated with low birth weight among neonates, compared with EPHX1
      His139Arg heterozygote/Arg139Arg homozygote before and after adjustment
      confounders. GSTT1 absent genotype group also was not associated with low birth
      weight among neonates, compared with GSTT1 present genotype group before and
      after adjustment confounders. When both EPHX1 139 polymorphism and GSTT1
      polymorphism were considered, a significant reduction in birth weight was found
      among neonates with EPHX1 His139His homozygote and GSTT1 absent genotype
      (OR=3.46, P=0.035). CONCLUSION: The combination between genetic polymorphisms in
      the EPHX1 gene and the GSTT1 gene in neonates is significantly associated with
      neonatal low birth weight.

PMID- 15719052
TI  - Constitutional mosaic trisomy 21 and azoospermia: a case report.
AB  - Constitutional full trisomy 21 is a common disorder in which abnormal
      spermatogenesis has been previously described. However, constitutional mosaic
      trisomy 21 in an otherwise normal but infertile male has not been explored. We
      report a case with low level mosaic trisomy 21 in a non-syndrome but azoospermic
      patient. We also propose that the patient's azoospermia may be related to the
      constitutional mosaic trisomy 21 and thus resulting in a late onset of testicular
      failure.

PMID- 15719051
TI  - [Heritability analysis of insulin sensitivity and the effect of age and sex: a
      twin study in Chinese aged 5-18].
AB  - OBJECTIVE: To study the contribution of genes and environment to the variation of
      insulin sensitivity, and the effect of body mass index (BMI), age and sex.
      METHODS: A total of 296 healthy same-sex twin pairs were studied, including 223
      monozygotic (MZ) and 73 dizygotic (DZ) twin pairs aged 5-18(mean age, 12+/-4
      years). Microsatellite polymorphism (STR) was used to diagnose zygosity of twins.
      Model-fitting method using Mx package was performed to analyze the genetic and
      environmental variance of homeostasis model assessment insulin resistance index
      (HOMA IR) and HOMA beta cell function index (HBCI), before and after adjusting
      BMI. The effect of age and sex on the model was tested. RESULTS: HOMA IR was
      correlated with age, sex and BMI, while HBCI was correlated with age. Genetic
      analysis showed in ACE model, heritability of HOMA IR in boys and girls was
      different before and after BMI adjustment; heritability of HBCI was not different
      significantly. Heritability of HOMA IR and HBCI were 0.25, 0.24, respectively,
      after adjusting BMI. CONCLUSION: Gene and environment influence insulin
      sensitivity of children and adolescents together, whereas environment seems to
      play a more important role. The effect of BMI on estimating heritability of
      insulin sensitivity is considerable, differing from sex or age.

PMID- 15719053
TI  - [Laminopathies--one gene, multiple diseases].
AB  - Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes
      with diverse tissue pathologies and result mainly from mutations in the LMNA gene
      encoding nuclear lamin A/C. To date, at least 9 different human diseases, which
      superficially seem to share little with one another, result from LMNA mutations.
      The position of the mutation within LMNA appears to be associated with the
      phenotypes. This review gives an overview of genotype-phenotype relationship and
      describes recent advances in animal models and pathogenic mechanisms.

PMID- 15719054
TI  - [Molecular genetics of Charcot-Marie-Tooth disease].
AB  - Charcot-Marie-Tooth disease (CMT) affects the peripheral nervous system. It is
      generally inherited in an autosomal dominant pattern, but also is inherited in
      recessive or an X-linked pattern. The degree of severity can vary greatly from
      patient to patient, even within the same family. Traditionally, the different
      classes of CMT have been divided into demyelinating forms and axonal forms. Until
      10 years ago, the genetic basis of CMT disease was largely unknown. An
      intrachromosomal duplication on chromosome 17 was found in 1991, and a point
      mutation in the peripheral myelin protein-22 gene was discovered in 1992. The
      work starts a new stage of the molecular basis of this large group of peripheral
      neuropathies. In this review, we will summarize what is known today about the
      genetics of CMT, and what we have learned about the underlying disease
      mechanisms.

PMID- 15719055
TI  - [The application of RNAi to the medical genetics].
AB  - Experimental RNA interference (RNAi) leading to the selective knockdown of gene
      function is induced by introducing into cells either double stranded RNA (dsRNA),
      or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA
      triggers degradation of homologous messenger RNA (mRNA). Widely used as a
      research tool in the genetic model organisms Caenorhabditis elegans, Drosophila
      melanogaster and mouse to investigate the function of individual genes, RNAi has
      also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid
      progress in the application of RNAi to mammalian cells, including neurons and
      muscle cells, offers new approaches to drug target identification and validation.
      Advances in targeted delivery of RNAi-inducing molecules have raised the
      possibility of using RNAi directly as a therapy for a variety of human genetic
      and other neural and neuromuscular disorders. Here, we review examples of the
      application of RNAi to worm, fly and mouse models of such diseases aimed at
      understanding their pathophysiology.

PMID- 15719056
TI  - Parsing a cognitive task: a characterization of the mind's bottleneck.
AB  - Parsing a mental operation into components, characterizing the parallel or serial
      nature of this flow, and understanding what each process ultimately contributes
      to response time are fundamental questions in cognitive neuroscience. Here we
      show how a simple theoretical model leads to an extended set of predictions
      concerning the distribution of response time and its alteration by simultaneous
      performance of another task. The model provides a synthesis of psychological
      refractory period and random-walk models of response time. It merely assumes that
      a task consists of three consecutive stages-perception, decision based on noisy
      integration of evidence, and response-and that the perceptual and motor stages
      can operate simultaneously with stages of another task, while the central
      decision process constitutes a bottleneck. We designed a number-comparison task
      that provided a thorough test of the model by allowing independent variations in
      number notation, numerical distance, response complexity, and temporal asynchrony
      relative to an interfering probe task of tone discrimination. The results
      revealed a parsing of the comparison task in which each variable affects only one
      stage. Numerical distance affects the integration process, which is the only step
      that cannot proceed in parallel and has a major contribution to response time
      variability. The other stages, mapping the numeral to an internal quantity and
      executing the motor response, can be carried out in parallel with another task.
      Changing the duration of these processes has no significant effect on the
      variance.

PMID- 15719057
TI  - SIRT1 regulates HIV transcription via Tat deacetylation.
AB  - The human immunodeficiency virus (HIV) Tat protein is acetylated by the
      transcriptional coactivator p300, a necessary step in Tat-mediated
      transactivation. We report here that Tat is deacetylated by human sirtuin 1
      (SIRT1), a nicotinamide adenine dinucleotide-dependent class III protein
      deacetylase in vitro and in vivo. Tat and SIRT1 coimmunoprecipitate and
      synergistically activate the HIV promoter. Conversely, knockdown of SIRT1 via
      small interfering RNAs or treatment with a novel small molecule inhibitor of the
      SIRT1 deacetylase activity inhibit Tat-mediated transactivation of the HIV long
      terminal repeat. Tat transactivation is defective in SIRT1-null mouse embryonic
      fibroblasts and can be rescued by expression of SIRT1. These results support a
      model in which cycles of Tat acetylation and deacetylation regulate HIV
      transcription. SIRT1 recycles Tat to its unacetylated form and acts as a
      transcriptional coactivator during Tat transactivation.

PMID- 15719059
TI  - Timing the brain: mental chronometry as a tool in neuroscience.

PMID- 15719058
TI  - HIV-1 Tat stimulates transcription complex assembly through recruitment of TBP in
      the absence of TAFs.
AB  - The human immunodeficiency virus type I (HIV-1) transactivator protein Tat is an
      unusual transcriptional activator that is thought to act solely by promoting RNA
      polymerase II processivity. Here we study the mechanism of Tat action by
      analyzing transcription complex (TC) assembly in vivo using chromatin
      immunoprecipitation assays. We find, unexpectedly, that like typical activators
      Tat dramatically stimulates TC assembly. Surprisingly, however, the TC formed on
      the HIV-1 long terminal repeat is atypical and contains TATA-box-binding protein
      (TBP) but not TBP-associated factors (TAFs). Tat function involves direct
      interaction with the cellular cofactor positive transcription elongation factor b
      (P-TEFb). Artificial tethering of P-TEFb subunits to HIV-1 promoter DNA or
      nascent RNA indicates that P-TEFb is responsible for directing assembly of a TC
      containing TBP but not TAFs. On the basis of this finding, we identify P-TEFb
      dependent cellular promoters that also recruit TBP in the absence of TAFs. Thus,
      in mammalian cells transcription of protein-coding genes involves alternative TCs
      that differ by the presence or absence of TAFs.

PMID- 15719060
TI  - Organized unidirectional waves of ATP hydrolysis within a RecA filament.
AB  - The RecA protein forms nucleoprotein filaments on DNA, and individual monomers
      within the filaments hydrolyze ATP. Assembly and disassembly of filaments are
      both unidirectional, occurring on opposite filament ends, with disassembly
      requiring ATP hydrolysis. When filaments form on duplex DNA, RecA protein
      exhibits a functional state comparable to the state observed during active DNA
      strand exchange. RecA filament state was monitored with a coupled
      spectrophotometric assay for ATP hydrolysis, with changes fit to a mathematical
      model for filament disassembly. At 37 degrees C, monomers within the RecA-double
      stranded DNA (dsDNA) filaments hydrolyze ATP with an observed k(cat) of 20.8 +/-
      1.5 min(-1). Under the same conditions, the rate of end-dependent filament
      disassembly (k(off)) is 123 +/- 16 monomers per minute per filament end. This
      rate of disassembly requires a tight coupling of the ATP hydrolytic cycles of
      adjacent RecA monomers. The relationship of k(cat) to k(off) infers a filament
      state in which waves of ATP hydrolysis move unidirectionally through RecA
      filaments on dsDNA, with successive waves occurring at intervals of approximately
      six monomers. The waves move nearly synchronously, each one transiting from one
      monomer to the next every 0.5 s. The results reflect an organization of the
      ATPase activity that is unique in filamentous systems, and could be linked to a
      RecA motor function.

PMID- 15719061
TI  - Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid
      composition in C. elegans.
AB  - Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X
      receptor, and peroxisome proliferator-activated receptors (PPARs), precisely
      control energy metabolism. Consequently, these receptors are important targets
      for the treatment of metabolic diseases, including diabetes and obesity. A
      thorough understanding of NHR fat regulatory networks has been limited, however,
      by a lack of genetically tractable experimental systems. Here we show that
      deletion of the Caenorhabditis elegans NHR gene nhr-49 yielded worms with
      elevated fat content and shortened life span. Employing a quantitative RT-PCR
      screen, we found that nhr-49 influenced the expression of 13 genes involved in
      energy metabolism. Indeed, nhr-49 served as a key regulator of fat usage,
      modulating pathways that control the consumption of fat and maintain a normal
      balance of fatty acid saturation. We found that the two phenotypes of the nhr-49
      knockout were linked to distinct pathways and were separable: The high-fat
      phenotype was due to reduced expression of enzymes in fatty acid beta-oxidation,
      and the shortened adult life span resulted from impaired expression of a stearoyl
      CoA desaturase. Despite its sequence relationship with the mammalian hepatocyte
      nuclear factor 4 receptor, the biological activities of nhr-49 were most similar
      to those of the mammalian PPARs, implying an evolutionarily conserved role for
      NHRs in modulating fat consumption and composition. Our findings in C. elegans
      provide novel insights into how NHR regulatory networks are coordinated to govern
      fat metabolism.

PMID- 15719062
TI  - Ancient DNA comes of age.

PMID- 15719064
TI  - Facts from text--is text mining ready to deliver?

PMID- 15719065
TI  - A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional
      elongation.

PMID- 15719063
TI  - Discovery-based science education: functional genomic dissection in Drosophila by
      undergraduate researchers.

PMID- 15719066
TI  - A space-time permutation scan statistic for disease outbreak detection.
AB  - BACKGROUND: The ability to detect disease outbreaks early is important in order
      to minimize morbidity and mortality through timely implementation of disease
      prevention and control measures. Many national, state, and local health
      departments are launching disease surveillance systems with daily analyses of
      hospital emergency department visits, ambulance dispatch calls, or pharmacy sales
      for which population-at-risk information is unavailable or irrelevant. METHODS
      AND FINDINGS: We propose a prospective space-time permutation scan statistic for
      the early detection of disease outbreaks that uses only case numbers, with no
      need for population-at-risk data. It makes minimal assumptions about the time,
      geographical location, or size of the outbreak, and it adjusts for natural purely
      spatial and purely temporal variation. The new method was evaluated using daily
      analyses of hospital emergency department visits in New York City. Four of the
      five strongest signals were likely local precursors to citywide outbreaks due to
      rotavirus, norovirus, and influenza. The number of false signals was at most
      modest. CONCLUSION: If such results hold up over longer study times and in other
      locations, the space-time permutation scan statistic will be an important tool
      for local and national health departments that are setting up early disease
      detection surveillance systems.

PMID- 15719067
TI  - Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity.
AB  - Alpha-defensins are abundant antimicrobial peptides in polymorphonuclear
      leukocytes and play an important role in innate immunity. We have previously
      shown that alpha-defensin-1 can inhibit HIV-1 replication following viral entry.
      Here we examined the molecular mechanism(s) of alpha-defensin-1-mediated HIV-1
      inhibition. Alpha-defensin-1 had a direct effect on HIV-1 virions at a low MOI in
      the absence of serum. The direct effect on HIV-1 virions was abolished by the
      presence of serum or an increase in virus particles. Studying the kinetics of the
      HIV life cycle revealed that alpha-defensin-1 inhibited steps following reverse
      transcription and integration. Analysis of PKC phosphorylation in primary CD4+ T
      cells in response to alpha-defensin-1 indicated that alpha-defensin-1 inhibited
      PKC activity. Pretreatment of infected CD4+ T cells with a PKC activator,
      bryostatin 1, partially reversed alpha-defensin-1-mediated HIV inhibition. Like
      alpha-defensin-1, the PKC isoform-selective inhibitor Go6976 blocked HIV-1
      infection in a dose-dependent manner. Furthermore, kinetic studies and analysis
      of HIV-1 products indicated that alpha-defensin-1 and Go6976 blocked HIV-1
      infection at similar stages in its life cycle, including nuclear import and
      transcription. Taken together, our studies demonstrate that, in the absence of
      serum, alpha-defensin-1 may act directly on the virus, but, in the presence of
      serum, its effects are on the cell, where it inhibits HIV-1 replication. At least
      1 of the cellular effects associated with HIV inhibition is interference with PKC
      signaling in primary CD4+ T cells. Studying the complex function of alpha
      defensin-1 in innate immunity against HIV has implications for prevention as well
      as therapeutics.

PMID- 15719069
TI  - Essential role of RSK2 in c-Fos-dependent osteosarcoma development.
AB  - Inactivation of the growth factor-regulated S6 kinase RSK2 causes Coffin-Lowry
      syndrome in humans, an X-linked mental retardation condition associated with
      progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a
      progressive skeletal disease, osteopenia due to impaired osteoblast function and
      normal osteoclast differentiation. The phenotype is associated with decreased
      expression of Phex, an endopeptidase regulating bone mineralization. This defect
      is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362
      in the C-terminus. However, in the absence of RSK2, c-Fos-dependent osteosarcoma
      formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos
      protein levels, which are thought to be responsible for decreased proliferation
      and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent
      stabilization of c-Fos is essential for osteosarcoma formation in mice and may
      also be important for human osteosarcomas.

PMID- 15719068
TI  - The secreted glycoprotein lubricin protects cartilage surfaces and inhibits
      synovial cell overgrowth.
AB  - The long-term integrity of an articulating joint is dependent upon the
      nourishment of its cartilage component and the protection of the cartilage
      surface from friction-induced wear. Loss-of-function mutations in lubricin (a
      secreted glycoprotein encoded by the gene PRG4) cause the human autosomal
      recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome
      (CACP). A major feature of CACP is precocious joint failure. In order to
      delineate the mechanism by which lubricin protects joints, we studied the
      expression of Prg4 mRNA during mouse joint development, and we created lubricin
      mutant mice. Prg4 began to be expressed in surface chondrocytes and synoviocytes
      after joint cavitation had occurred and remained strongly expressed by these
      cells postnatally. Mice lacking lubricin were viable and fertile. In the newborn
      period, their joints appeared normal. As the mice aged, we observed abnormal
      protein deposits on the cartilage surface and disappearance of underlying
      superficial zone chondrocytes. In addition to cartilage surface changes and
      subsequent cartilage deterioration, intimal cells in the synovium surrounding the
      joint space became hyperplastic, which further contributed to joint failure.
      Purified or recombinant lubricin inhibited the growth of these synoviocytes in
      vitro. Tendon and tendon sheath involvement was present in the ankle joints,
      where morphologic changes and abnormal calcification of these structures were
      observed. We conclude that lubricin has multiple functions in articulating joints
      and tendons that include the protection of surfaces and the control of synovial
      cell growth.

PMID- 15719071
TI  - Antibacterial and antiplaque effects of a novel, alcohol-free oral rinse with
      cetylpyridinium chloride.
AB  - Antimicrobial agents are commonly incorporated into hygiene products for the
      treatment and prevention of plaque and gingivitis. Recently, a new alcohol-free
      rinse containing 0.07% cetylpyridinium chloride (CPC) in a high bioavailable
      matrix (Crest Pro-Health Rinse) was introduced to provide antiplaque and
      antigingivitis benefits. This paper reviews results from an in vitro pre-clinical
      study and an in vivo clinical study evaluating the antibacterial and antiplaque
      benefits of this CPC rinse technology. In the in vitro experiment, a no-alcohol
      0.065% high bioavailable CPC prototype rinse was evaluated for its hostility
      against a broad range of microorganisms commonly associated with plaque and
      gingivitis. The rinse demonstrated greater than 99% germ kill for all organisms
      tested individually as well as in whole saliva. The benefit of this antibacterial
      action on plaque inhibition was assessed in a clinical trial. A double-blinded, 3
      period, 6-sequence crossover study was conducted evaluating the antiplaque effect
      of the novel 0.07% high bioavailable, alcohol-free CPC rinse versus a positive
      control (Listerine Cool Mint containing essential oils) and a negative control
      (placebo CPC rinse). A modification of the Addy 4-day plaque model was used for
      this evaluation. Plaque was measured at baseline (Day 1) of each treatment period
      and at Day 4 using the Turesky modification of Quigley-Hein index. During the
      treatment period, subjects brushed only their lingual surfaces twice daily for up
      to 60 seconds. Following brushing, subjects used 20 mls of the mouthrinse product
      for 30 seconds in the morning and evening. Fifty-five subjects completed the
      study. For non-brushed sites, both the essential oils and CPC rinse exhibited a
      25% reduction in plaque vs. placebo after four days of product usage, which was
      statistically significant (p < 0.0001). Both treatments also exhibited a
      statistically significant benefit versus placebo (p<0.0001) for brushed sites
      (>38% plaque reduction). These data support the antibacterial action of the high
      bioavailable, alcohol-free CPC rinse and demonstrate antiplaque effects for Crest
      Pro-Health Rinse that are "at least as good as" the leading essential oils
      antiseptic, making it well-suited for a broad range of patients, particularly
      those who are sensitive to products containing alcohol.

PMID- 15719070
TI  - Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the
      EP2 subtype.
AB  - Blockade of prostaglandin (PG) production by COX inhibitors is the treatment of
      choice for inflammatory pain but is also prone to severe side effects.
      Identification of signaling elements downstream of COX inhibition, particularly
      of PG receptor subtypes responsible for pain sensitization (hyperalgesia),
      provides a strategy for better-tolerated analgesics. Here, we have identified
      PGE2 receptors of the EP2 receptor subtype as key signaling elements in spinal
      inflammatory hyperalgesia. Mice deficient in EP2 receptors (EP2-/- mice)
      completely lack spinal PGE2-evoked hyperalgesia. After a peripheral inflammatory
      stimulus, EP2-/- mice exhibit only short-lasting peripheral hyperalgesia but lack
      a second sustained hyperalgesic phase of spinal origin. Electrophysiological
      recordings identify diminished synaptic inhibition of excitatory dorsal horn
      neurons as the dominant source of EP2 receptor-dependent hyperalgesia. Our
      results thus demonstrate that inflammatory hyperalgesia can be treated by
      targeting of a single PG receptor subtype and provide a rational basis for new
      analgesic strategies going beyond COX inhibition.

PMID- 15719072
TI  - The effects of BID length and shape on the surface area and volume of tissue
      exposed during dental radiography.
AB  - Using projection geometry, algebraic formulas, and different beam indicating
      devices (BIDs), the surface area and volume of tissue exposed for a hypothetical
      patient was determined. Combinations of 4 BID lengths and shapes were used: 4
      inch (10.2 cm.) pointed plastic, 8-inch (20.3 cm.) round plastic, 14-inch (35.6
      cm.) round aluminum, and 14-inch (35.6 cm.) rectangular aluminum. As each subject
      BID was progressively lengthened and collimated, the area and volume of tissue
      exposed was reduced. The calculated area and volume of exposed tissue for the 14
      inch rectangular aluminum open-ended lead-lined BID was 16.6 cm.2 and 327.7 cm.3,
      respectively. This represented 9% of the area and 8% of the volume of tissue
      exposed using the 4-inch round pointed plastic BID or a 91% (area) and 92%
      (volume) reduction in patient exposure.

PMID- 15719073
TI  - Effects of one versus two-layer applications of a self-etching adhesive to dentin
      of primary teeth: a SEM study.
AB  - Resin composite is increasingly the material of choice for the restoration of
      primary teeth, and new materials with simplified procedures are increasingly
      being offered. Self-etching primers have been developed to simplify the bonding
      procedures. Some manufacturers recommend the application of these materials in
      two layers. However little is known about the application times. Therefore, this
      study evaluated the quality of the interfacial seal and the micromorphology of
      the hybrid layer in composite restorations bonded with one or two layer
      applications of a self-etching adhesive to the dentin of the primary teeth. The
      superfacial dentin (within 1-2 mm of dentinoenamel junction (DEJ)) on the
      occlusal surfaces of fourteen primary molars was exposed by a flat cut
      perpendicular to the long axis of the tooth. The occlusal surfaces were divided
      into two halves by a 1 mm deep groove in the labial-lingual orientation. The
      teeth were randomly divided into two groups: Group 1: Single Bond (control group)
      was applied according to the manufacturer's instructions on one half of the
      surface. On the other half of the same tooth, one layer of Prompt-L-Pop
      (experimental group) was applied according to the manufacturer's instructions.
      Group 2: the teeth received the same bonding regimes as group 1, but the
      experimental group had two layer application of Prompt-L-Pop. All samples were
      analyzed in SEM. Student's t-test was used to compare the width of the gap and
      hybrid layer thickness generated by experimental groups and control. There was a
      statistically significant difference between control (Single Bond) and the
      experimental groups (one or two layer application of Prompt-L-Pop) (p<0.05).
      Single Bond showed the best results. Two layer application of Prompt-L-Pop showed
      better sealing ability than one layer application of it (p<0.05). Only Single
      Bond presented a visible hybrid layer that had an average thickness of 3.7microm.

PMID- 15719074
TI  - Correlation of different MRI characteristics of anterior disc displacement with
      reduction and without reduction.
AB  - The aim of this study was to evaluate the correlations between magnetic resonance
      imaging (MRI) findings in anterior displacement with reduction (ADDR) and
      anterior displacement without reduction (ADDWR). Two hundred patients with
      temporomandibular disorder (TMD) symptoms were examined clinically by a clinician
      experienced with this disorder. There were 130 joints with ADDR and 45 joints
      with ADDWR; 88 patients were identified according to the clinical and MRI
      diagnoses of both observers. The MRI characteristics such as position, signal
      intensity, morphology of disc, degenerative changes, effusion, scar tissue,
      avascular necrosis, and condylar hypermobility were evaluated in the individual
      with ADDR and ADDWR. The Chi-square test was used to determine the correlation
      between MRI characteristics in the ADDR and the ADDWR. There were significant
      relationships between degenerative changes and increased signal intensity,
      degenerative changes and side-way displacement, effusion and the deformation of
      the disc, effusion and subluxation, increased signal intensity and subluxation,
      elongation deformation and increased signal intensity, and elongation deformation
      and side-way displacement in ADDR. There were significant relationships between
      degenerative changes and effusion, degenerative changes and decreased signal
      intensity, scar tissue and avascular necrosis, deformation of disc and increased
      signal intensity, as well as deformation of disc and decreased signal intensity
      in ADDWR. These MRI findings also correlated with the clinical findings, however,
      this correlation appears to be a synergistic pattern rather than a set of clear
      cut relationships. The correlations between these MRIs and different clinical
      findings such as pain and dysfunction also must be evaluated. Existing
      correlations must be considered in the diagnosis and treatment planning of TMD,
      and signs and symptoms of TMD should be monitored after treatment.

PMID- 15719075
TI  - Effect of direct relining on stresses at the denture base and the metal frame of
      removable partial dentures.
AB  - The Kennedy Class I removable partial denture (RPD) can cause stress to
      supporting hard and soft tissues and may lead to harmful effects. The purpose of
      this study is to investigate the pattern of these stresses in three different
      positions before and following a relining procedure. Ten patients, five males and
      five females, with a lower distal extension RPD and an opposing upper class III
      type RPD were selected for this study. Strain gauges together with a strain gauge
      indicator were used to study the pattern of stresses in three selected positions.
      Some changes were significantly different at the site of the denture base and at
      the metal frame near the direct retainer. After relining, the stresses were
      shared partially by the abutments and partially by the tissues. Maximum stresses
      were reported during swallowing. No significant difference was noticed between
      males and females.

PMID- 15719076
TI  - A clinical evaluation of the clinical remount procedure.
AB  - One hundred patients were treated with complete dentures. The patients were
      divided into two equal groups; the first group (50 patients) received complete
      dentures and a clinical remount procedure was performed, while the second group
      received complete dentures without a clinical remount. A four point, nine scale
      Patient Denture Satisfaction questionnaire was used to evaluate the patients'
      satisfaction with their dentures. When the clinical remount procedure was used,
      results have shown a highly significant improvement in the comfort of the upper
      dentures and in the fit and comfort of the lower dentures. There was a
      significant improvement in the chewing ability as well. In conclusion it is
      highly recommended the clinical remount procedure be used because it improves the
      patient's satisfaction with their dentures in many important aspects as shown in
      this study.

PMID- 15719077
TI  - An anterior tooth size comparison in unilateral and bilateral congenitally absent
      maxillary lateral incisors.
AB  - The purpose of this study is to compare the anterior tooth size width in patients
      with congenitally missing maxillary lateral incisors using the Bolton Index and
      divine proportion. The study sample consisted of thirty pairs of orthodontic
      models with unilateral (twelve patients; 7 females, 5 males) and bilateral
      (eighteen patients; 13 females, 5 males) absence of maxillary lateral incisors.
      The mean ages of the selected cases were 17.7 and 17.5 years, respectively.
      Descriptive statistics were used for the data analysis. The result showed the
      mean of the Bolton Index in cases with bilateral absence was closer to the Bolton
      mean than in cases with unilateral absence. In the unilateral absence cases the
      width of the existing lateral incisor (5.5 mm) was an average of 1.00 mm less
      compared to the standard mean (6.5 mm). The divine proportion showed the
      maxillary central incisors were small in width as indicated by the adjusted value
      or they were slightly larger in width than the mandibular central incisors. In
      cases with unilateral and bilateral absence the Bolton Index exhibited maxillary
      insufficiency, which was confirmed by evaluating the divine proportion of the
      maxillary and mandibular incisors. The result of the present study will be of
      great help to both the orthodontist, whether to open or close the space, and to
      the prosthodontist to restore the missing teeth of patients having missing
      maxillary lateral incisors.

PMID- 15719078
TI  - Emotional effects of malocclusion in Nigerian orthodontic patients.
AB  - AIM: To assess the emotional effects of malocclusion among Nigerian orthodontic
      patients. DESIGN: A questionnaire survey. SUBJECTS AND METHODS: A questionnaire
      was completed by 221 Nigerian orthodontic patients undergoing routine orthodontic
      care at the Orthodontic Unit, Department of Preventive Dentistry, University
      College Hospital, Ibadan and the Department of Child Dental Health, Lagos
      University Teaching Hospital, Lagos, both in South-West Nigeria. The participants
      were comprised of 97 (43%) males and 124 (56.1%) females with age range of 6-40
      years (mean age, 13.82 +/- 8.01 SD). Data were analyzed using descriptive
      statistics and Chi-square test. RESULTS: About 44% of all participants had not
      yet accepted their malocclusions, while 56.6% of all subjects reported for
      orthodontic care due to aesthetic reasons. Twenty-seven percent of the subjects
      were depressed the first time they notice their malocclusions. Over 40% of the
      participants reported feeling less confident as a result of their malocclusions
      and about 55% of them felt their malocclusions negatively affected their general
      facial appearances. Normal activities restricted in some of the subjects due to
      malocclusion included laughing in public (48.9%), meeting people in public (32%),
      and forming close relationships (20.4%). The majority (64.7%) of the subjects
      discussed their malocclusions with their parents, followed by dentists (35.3%).
      CONCLUSION: The psychosocial effects of malocclusion in Nigerian orthodontic
      patients were considerable with no significant gender differences. Considering
      such factors, professional counseling of Nigerian orthodontic patients is
      encouraged.

PMID- 15719079
TI  - An evaluation of survival of space maintainers: a six-year follow-up study.
AB  - The aim of this study was to evaluate the median survival time of fixed and
      removable space maintainers related to age groups, gender, and their distribution
      in upper and lower dental arches. The adherence of patients to a periodic recall
      program and the success rate of different types of space maintainers related to
      different arches were also evaluated. This study included 663 patients aged
      between 4-15 years old that were treated between the years of 1997 and 2002. The
      patients were categorized into four main groups: lost to follow-up, failed,
      successful, and censored at the end of study. Three hundred forty-five space
      maintainers were considered lost to follow-up, 83 were considered failed, 206
      successful, and 20 censored-at-end. The overall median survival time of the
      appliances was 6.51 months. Median survival time was 7.25 months in the 4-6 age
      group, 6.35 months in the 7-12 age group, and 7.0 months in the 13+ age groups.
      Median survival time was 5.76 months in girls and 7.11 months in boys. Median
      survival time of space maintainers was 7.17 months for maxilla and 6.69 months in
      the mandible. Median survival time was 5.25 months for space maintainers
      fabricated in both arches.

PMID- 15719080
TI  - Presence of Actinobacillus actinomycetemcomitans on the Community Periodontal
      Index (CPI) teeth in periodontally healthy individuals.
AB  - The aim of this study was to compare the prevalence of Actinobacillus
      actinomycetemcomitans (A. actinomycetemcomitans) located at Community Periodontal
      Index (CPI) teeth versus randomly selected teeth to determine if the CPI teeth
      are representative of this bacteria subgingival colonization in periodontally
      healthy young individuals. Forty-four individuals between 18 and 27 years of age
      were included in the study (mean age 23.11 +/- 2.91 years). Pooled subgingival
      plaque samples were collected with paper points from the mesio-buccal aspect of
      the CPI teeth (10 teeth for adults and 6 teeth for persons under 20 years of age)
      and transported in reduced Ringer's solution to the culture medium. Sixty days
      following the first microbial analysis, new pooled microbial samples were
      obtained from the mesio-buccal aspect of 10 or 6 randomly selected teeth. The
      presence of A. actinomycetemcomitans was determined using a selective culture
      medium. Microbiological data were assessed by the Wilcoxon test (p < 0.05). A
      border line significance (p=0.51) was observed between CPI teeth and randomly
      selected teeth in terms of detecting the subgingival occurrence of A.
      actinomycetemcomitans. CPI teeth showed to be representative of A.
      actinomycetemcomitans subgingival colonization. Therefore, these results suggest
      that in periodontally healthy young individuals, CPI teeth could be an
      appropriate source of samples for the subginginval detection of this pathogen.

PMID- 15719081
TI  - The effectiveness of three instrumentation techniques on the elimination of
      Enterococcus faecalis from a root canal: an in vitro study.
AB  - The in vitro reduction of a bacterial population in a root canal by mechanical
      instrumentation using three techniques was evaluated. Root canals inoculated with
      a Enterococcus faecalis (E. faecalis) suspension were instrumented using hand
      Hedstroem files, Giromatic files, and Hero 642 rotary instruments. Irrigation was
      performed using sterile saline solution. Root canals were sampled before and
      after instrumentation. After serial dilutions, samples were plated onto Mitis
      Salivarius agar and the colony forming units grown were counted. All instruments
      tested were able to significantly reduce the number of bacterial cells in the
      root canal, however, the results of this study indicated that Hedstroem files,
      Giromatic, and Hero 642 techniques were not significantly different in their
      ability to reduce intracanal bacteria.

PMID- 15719082
TI  - Gender-specific oral health attitudes and behavior among dental students in
      Jordan.
AB  - The aim of this study was to determine the difference in oral health attitudes
      and behavior between male and female dental students at Jordan University of
      Science and Technology (JUST). A self-administered questionnaire based on a
      modified version of the Hiroshima University Dental Behavior Inventory (HU-DBI)
      was distributed among 375 dental students. The response rate was 83.7% with 48%
      males and 52% females responding. Female students reported brushing their teeth
      more frequently than male students (P<0.001). Approximately 47% of the male
      students brushed their teeth less than twice daily compared to 21% of the female
      students. Also, female students believed in the necessity of using toothpaste
      during brushing more often than male students (P<0.01). On the other hand,
      smoking was much more frequent among males than among females (31% vs. 4%)
      (P<0.001). Male students indicated they had been smoking for longer periods of
      time than female students. This survey shows male students visit the dentist only
      when they have dental pain. While this was more than their female peers, it was
      not statistically significant (P= 0.056). In general the present study showed
      dental students in Jordan had poor oral health. Further research is needed to
      examine the students clinically for periodontal and caries conditions. Students
      should be encouraged to be a model for oral health for their families, friends,
      and patients.

PMID- 15719083
TI  - Gender differences in dental anxiety: is the chair position important?
AB  - Dental anxiety in the general population is more prevalent in females than in
      males. The presence of dental anxiety was studied in a group of 189 females and
      176 males using the following scales: the Dental Anxiety Scale (divided into DAS
      1 containing 6 items, which explores a patient's dental anxiety and DAS 2
      containing 13 items, which looks at dental anxiety concerning dentist-patient
      relations), the Self-Rating Depression Scale (SDS), and the Quality of Life Index
      (QL-Index). The results obtained showed significant differences only in relation
      to dental anxiety regarding the use of instruments (such as needles and
      handpieces) and the tilted-back position of the chair (DAS 1). No significant
      gender differences emerged between the two groups in relation to dental anxiety
      regarding dentist-patient relations (DAS 2), depression (SDS), and the quality of
      life (QL-Index). The results may explain why women avoid dental care and indicate
      new designs to make the chair position more comfortable would be useful.

PMID- 15719084
TI  - Geographic tongue: clinical characteristics of 188 cases.
AB  - The purpose of this study was to investigate the clinical characteristics and
      assess other factors associated with geographic tongue in Thailand. One hundred
      and eighty-eight Thais with geographic tongue and 188 controls were interviewed
      regarding their medical history, symptoms, and the nature and migratory pattern
      of their lesions. Variations in the clinical appearance, lesion location, and any
      associated tongue fissures were recorded. The age range for the 188 subjects was
      9 to 79 years. The highest incidence (39.4%) occurred in the 20-29 age group.
      Women were affected more than men (1.5:1). The leading group of medical
      conditions consisted of allergy-related disorders; however, the incidence of
      these problems among both subjects and controls was not significantly different
      (55.2% vs. 44.8%). Our results demonstrated a significant co-existence of
      geographic tongue and fissured tongue. Most of the geographic tongue lesions
      manifested a typical appearance consisting of a central atrophic area bounded by
      a raised white circinate line (69.1%) with multiple tongue sites affected
      (62.8%). The most common locations were at the lateral margins and tip of the
      tongue. The majority of our subjects (75.5%) were asymptomatic. The results of
      this study correspond with the findings of previous geographic tongue studies in
      other populations.

PMID- 15719085
TI  - Clinical experience with parotid gland enlargement in HIV infection: a report of
      five cases in Nigeria.
AB  - A changing picture of oral lesions associated with HIV/AIDS has been documented.
      With the use of antiretroviral therapy, salivary gland swellings and other less
      common conditions associated with HIV/AIDS are now becoming more common. Our
      review of the literature showed the presence of parotid swelling in HIV-1
      infection has increased from a range of 5-10% to 20% in AIDS. However, to the
      best of our knowledge, none from sub-Saharan Africa, which is the epicenter of
      the HIV infection and where access to antiretroviral therapy is poorest, has been
      primarily reported in literature. This report documents five cases of bilateral
      parotid gland enlargement as the presenting clinical manifestation of HIV/AIDS.
      The combination of a fine needle aspiration (FNA) biopsy, ultrasound imaging, and
      histological diagnosis increased the accuracy of diagnosis. While two patients
      had access to antiretroviral therapy, other modes of management were cystic
      aspiration and parotidectomy. One of the patients treated with parotidectomy had
      facial nerve injury, and the short-term aesthetic outcome between surgical
      treatment and antiretroviral therapy did not appear different. However, all our
      patients were lost to follow-up within a 2-year period. For a resource
      constrained environment like Nigeria where stigma and discrimination is high and
      access to antiretroviral therapy is limited, there is a need to understand how
      best to manage a lymphoepithelial lesion in HIV/AIDS patients.

PMID- 15719086
TI  - The subepithelial connective tissue graft: part I. Patient selection and surgical
      techniques.
AB  - Periodontal mucogingival techniques continually evolve. This provides the patient
      more treatment alternatives for common problems such as gingival recession.
      General practitioners should be familiar with these techniques in order to
      identify patients who might benefit from them. Currently, subepithelial
      connective tissue grafts (SCTG) remain the most reliable techniques used to cover
      denuded root surfaces. This paper reviews patient selection and the numerous
      surgical approaches for subepithelial connective tissue grafting.

PMID- 15719087
TI  - Acupuncture and acupressure techniques for reducing orthodontic post-adjustment
      pain.
AB  - Orthodontic post-adjustment pain is one of the most common complaints of adult
      patients undergoing orthodontic treatment. This article aims to introduce the
      combination of acupuncture and acupressure techniques for reducing orthodontic
      post-adjustment pain using a single acupuncture point, Hegu (LI-4).

PMID- 15719088
TI  - AAOMP case challenge: a "speckled" lesion.

PMID- 15719091
TI  - The first X-ray crystal structure determination of a dinuclear complex trapped in
      the [low spin-high spin] state: [Fe(II)2(PMAT)2](BF4)4.DMF.
AB  - The two metal centres in the doubly 1,2,4-triazole-bridged spin crossover complex
      [Fe(II)2(PMAT)2](BF4)4.DMF (1.DMF) are trapped in different spin states below ca.
      200 K, with no evidence that this particular [LS-HS] species can be converted
      into the [LS-LS] form at ambient pressure.

PMID- 15719090
TI  - Synthesis of enamines, enol ethers and related compounds by cross-coupling
      reactions.
AB  - For several decades, enamines and related compounds have been used as
      intermediates in organic synthesis and many methods are known for their
      preparation. Most of the synthetic protocols, however, require harsh reaction
      conditions. Recently, a new approach has emerged, inspired by the analogous
      arylation of amines catalysed by palladium or copper complexes (Buchwald-Hartwig
      reaction). Simultaneous and independent work from several research groups has led
      to the development of very powerful protocols for the preparation of enamines and
      their derivatives that require only readily available starting materials and
      proceed under very mild reaction conditions. Noteworthy is the fact that in less
      than five years an almost unknown reaction has reached such a high level of scope
      and generality that it is now very frequently applied in total syntheses of
      natural products.

PMID- 15719092
TI  - A chemical method for the convenient surface functionalisation of polymers.
AB  - A method for the application of carbenes as reactive intermediates for surface
      modification of polymeric substrates has been developed; the efficacy of the
      process has been demonstrated by irreversible dyeing of polystyrene, polythene,
      nylon, silica, and controlled pore glass, and to a limited extent,
      polytetrafluoroethylene.

PMID- 15719093
TI  - Structural and zeolitic features of a 3D heterometallic porous architecture
      constructed from a {M(oxalate)4}4- building unit.
AB  - The utilization of the tetrahedral pre-formed coordination compound
      {U(C(2)O(4))(4)}(4-) permitted the efficient synthesis of a 3D heteronuclear
      supramolecular nano-porous architecture undergoing a reversible sorption process
      without collapsing.

PMID- 15719094
TI  - Cationic polyhedral oligomeric silsesquioxane (POSS) units as carriers for drug
      delivery processes.
AB  - Quaternary ammonium functionalized polyhedral oligomeric silsesquioxane
      (OctaAmmonium-POSS) units, widely employed as additives in ceramic and polymeric
      systems, possess many attributes which make them attractive as biocompatible drug
      carriers: nanoscale size, three-dimensional functionality, efficient cellular
      uptake, low toxicity, and high solubility.

PMID- 15719095
TI  - "Uncorking" of liposomes by matrix metalloproteinase-9.
AB  - A triggered release methodology of liposomal contents via the enzyme MMP-9 is
      described.

PMID- 15719097
TI  - Novel copper macrocyclic leaflet with N-phosphonomethyl-monoaza-18-crown-6.
AB  - A novel 1D copper macrocyclic leaflet chain has been synthesized hydrothermally
      and its crystal structure determined.

PMID- 15719096
TI  - A highly electroluminescent molecular square.
AB  - Chiral molecular triangles and squares containing the Pt(diimine) metallocorners
      were synthesized and characterized, and used as the triplet MLCT luminophore in
      highly efficient light-emitting devices.

PMID- 15719098
TI  - Ring expansion of sulfur substituted p-quinamines: regiospecific synthesis of 4
      aminotropones.
AB  - Synthesis of 4-aminotropones through a cyclization-ring expansion process occurs
      in a single step and with excellent yields from 4-amino-2,5-cyclohexadienones (p
      quinamines) bearing a 4-sulfinyl or sulfonyl methyl group.

PMID- 15719099
TI  - Enantioselective synthesis of homoallylic alcohols via a chiral In(III)-PYBOX
      complex.
AB  - In the presence of 20 mol% of a chiral catalytic complex prepared from In(OTf)(3)
      and chiral PYBOX, allyltributylstannane reacted with aldehydes to afford the
      corresponding homoallylic alcohols in moderate to high enantioselectivities (60
      93% ee).

PMID- 15719100
TI  - Formation of novel anionic gold-tin cluster compounds.
AB  - A straightforward procedure for the formation of mixed metal Au/Sn clusters is
      presented: reaction of the heteroborate [SnB11H11]2- with phosphine gold
      electrophiles gave the clusters [Bu3NH]3[{(Et3P)Au(SnB11H11)}3] and
      [Bu3MeN]4[{(dppm)Au2(SnB11H11)2}2], which were characterised by X-ray
      diffraction.

PMID- 15719101
TI  - Mycobacterium tuberculosis H37Rv3377c encodes the diterpene cyclase for producing
      the halimane skeleton.
AB  - The cloning and functional expression of Mycobacterium tuberculosis Rv3377c in
      Escherichia coli revealed that this gene encodes the diterpene cyclase for
      producing (+)-5(6),13-halimadiene-15-ol, which accepts geranylgeranyldiphosphate
      as the intrinsic substrate.

PMID- 15719102
TI  - In situ evaluation of interfacial affinity in CeO2 based hybrid nanoparticles by
      pulsed field gradient NMR.
AB  - Complexation affinity of laurate ligands (C(12)H(23)O(2)) grafted onto the
      surface of cerium(IV) oxide nanoparticles can be probed and quantified in situ,
      by pulsed field gradient (1)H NMR through the dependence of the diffusion
      coefficient on the size of a species.

PMID- 15719103
TI  - Synthesis and crystal structure of the first lanthanide complex of N-confused
      porphyrin with an eta2 agostic C-H interaction.
AB  - The reaction of Ln[N(SiMe3)2]3.[LiCl(THF)3](x)(Ln = Yb and Er) with N-confused
      tetraphenylporphyrin (H2NCTPP) followed by Na(L(OMe))(L(OMe)=(eta5
      C5H5)Co[P(=O)(OMe)2]) gives (NCTPP)Ln(L(OMe)), whose X-ray structures exhibit an
      eta2 agostic interaction between the metal centre and the inner C-H bond of the
      NCTPP ligand.

PMID- 15719104
TI  - Luminescent cyclometalated platinum(II) complexes with amino acid ligands for
      protein binding.
AB  - Pt(C/N)(phe)(1, C/N = 2-(2'-thienyl)pyridine, phe = phenylalanine) shows a high
      binding affinity (ca. 10(6) dm(3) mol(-1)) and selectivity towards human serum
      albumin (HSA) and such binding is accompanied by an enhancement of
      photoluminescence at 562 nm; both the protein binding affinity and cytotoxicities
      of [Pt(C/N)(phe)(1), Pt(C/N)(trp)(2, trp = tryptophan) and Pt(C/N)(gly)(3, gly =
      glycine)] are affected by the amino acid ligand with having an IC(50) of up to 1
      microM against a number of carcinoma cell lines.

PMID- 15719106
TI  - Using ring strain to inhibit a decomposition path: first synthesis of an Alkyl
      BIAN ligand (Alkyl-BIAN = bis(alkyl)acenaphthenequinonediimine).
AB  - N-Alkyl imines of acenaphthenequinone are not stable because an isomerization
      occurs that releases part of the ring strain of the initially formed imine by
      changing the hybridization of one of the ring carbon atoms from sp(2) to sp(3);
      however, if an even more strained ring is present in the alkyl group, the
      isomerization becomes unfavorable and the compound is stable.

PMID- 15719105
TI  - Enantioselective total synthesis of pteridic acid A.
AB  - Pteridic acid A, a potent plant growth promoter with auxin-like activity, was
      synthesized enantioselectively by using the Evans asymmetric aldol reaction as
      the key C-C bond forming step.

PMID- 15719107
TI  - A polymer support with controllable solubility in mutually immiscible solvents.
AB  - We report on novel soluble macromolecules displaying rather peculiar solution
      behaviour, which allows us to gain full control of their partition into three
      mutually immiscible liquid media: water, dichloromethane and
      perfluoro(methylcyclohexane); such polymers may be used as soluble supports for
      reagents or catalysts, yielding supported species whose solubility preference for
      one out of three liquid phases can be quantitatively and reversibly switched,
      thereby simplifying separation considerably.

PMID- 15719108
TI  - Room temperature palladium catalysed coupling of acyl chlorides with terminal
      alkynes.
AB  - Conditions are reported for the facile, high-yielding coupling of acyl chlorides
      with terminal alkynes in a reaction involving palladium and copper iodide; the
      reaction is tolerant of a wide variety of acyl chlorides and terminal alkynes and
      provides a convenient one-pot route to acetylenic ketones.

PMID- 15719109
TI  - Pd-Dissolution through a mild and effective one-step reaction and its application
      for Pd-recovery from spent catalytic converters.
AB  - We describe here an innovative method for Pd-dissolution using the reagent N,N'
      dimethylperhydrodiazepine-2,3-dithione diiodine adduct which, being safe and
      powerful, is appealing for practical applications: remarkably almost quantitative
      Pd-recovery from model spent three-way catalysts has been obtained, showing that
      the effectiveness of the method is maintained when palladium is contained in a
      complex system such as a car catalyst, a ceramic material which has undergone
      severe thermal stress.

PMID- 15719110
TI  - Copper clusters built on bulky amidinate ligands: spin delocalization via
      superexchange rather than direct metal-metal bonding.
AB  - Entry into a new class of tetra- and dicopper clusters was assisted by a fine
      steric tuning of bulky amidinate ligands that provide spin-delocalizing
      superexchange pathways in class III mixed-valence clusters, the properties of
      which are best understood without invoking metal-metal bonding.

PMID- 15719111
TI  - Synthesis of amino acid-based polymers via atom transfer radical polymerization
      in aqueous media at ambient temperature.
AB  - Well-defined acryloyl beta-alanine (ABA) polymers were synthesized directly via
      atom transfer radical polymerization (ATRP) under near physiological conditions
      using various water soluble initiators with high yield and narrow molecular
      weight distributions.

PMID- 15719112
TI  - NO2 disproportionation for the IR characterisation of basic zeolites.
AB  - NO2 disproportionation on alkaline zeolites is used to generate nitrosonium (NO+)
      and nitrate ions on the surface, and the infrared vibrations observed are very
      sensitive to the cation chemical hardness and to the basicity of zeolitic oxygen
      atoms.

PMID- 15719113
TI  - Enhanced visible photoluminescence in ultrathin poly(3-hexylthiophene) films by
      incorporation of Au nanoparticles.
AB  - Incorporation of non-luminescent dodecanethiolate-protected gold clusters into
      regioregular poly(3-hexylthiophene) films results in a 6-fold increase in the
      visible photoluminescence (PL) of the polymer, which arises predominantly from NP
      induced structural changes in the composite films.

PMID- 15719114
TI  - Construction of conjugated molecular structures on gold nanoparticles via the
      Sonogashira coupling reactions.
AB  - Functional, conjugated molecular structures have been fabricated on Au
      nanoparticles via the Sonogashira coupling reactions.

PMID- 15719115
TI  - Facile synthesis of stable cubic mesoporous silica SBA-1 over a broad temperature
      range with the aid of D-fructose.
AB  - A highly ordered cubic mesoporous silica SBA-1 with enhanced stability towards
      washing with water has been synthesized simply by adding D-fructose as an
      auxiliary agent during the synthesis.

PMID- 15719116
TI  - Revisiting the Maitland-Japp reaction. Concise construction of highly
      functionalised tetrahydropyran-4-ones.
AB  - Application of modern synthetic methods to the Maitland-Japp reaction has
      provided a one pot, one step procedure for the efficient construction of highly
      substituted tetrahydropyran-4-ones.

PMID- 15719118
TI  - Millisecond long-lived charge separated state at room temperature in a flexibly
      linked diphenylaminopolyene-C60 dyad.
AB  - Long-lived photoinduced charge separation involving one-step electron transfer is
      achieved in diphenylaminopolyene based C60-donor dyads with a short, flexible
      linkage.

PMID- 15719117
TI  - An ultrasensitive nucleic acid biosensor based on the catalytic oxidation of
      guanine by a novel redox threading intercalator.
AB  - An ultrasensitive nucleic acid biosensor for the direct detection of attomoles
      nucleic acid in 1.0-5.0 [corrected] microl droplets is described which can be
      used for detection of cancer marker genes in mRNA extracted from human breast
      tissues without a RT-PCR step.

PMID- 15719119
TI  - Preparation of an ordered zeolite MFI film by epitaxial growth.
AB  - An ordered zeolite MFI film has been prepared on the substrate of a {001} basal
      face of high-quality large silicalite-1 crystals by epitaxial growth.

PMID- 15719121
TI  - Cage-like ordered silica with large mesopore volume synthesized by doubling
      amount of polymer, adding sodium chloride and lowering acid concentration.
AB  - Cage-like ordered mesoporous silica, FDU-1, with about twice the pore volume and
      a narrower pore size distribution compared with those for previously reported
      samples was synthesized in a much shorter time by doubling the amount of block
      copolymer, adding sodium chloride and lowering the acid concentration.

PMID- 15719120
TI  - Saccharin as a salt former. Enhanced solubilities of saccharinates of active
      pharmaceutical ingredients.
AB  - Saccharin, acting as a weak acid, forms salts with basic APIs and these salts
      have the desirable property of enhanced water solubility.

PMID- 15719122
TI  - Selective formation of a stable micro-peroxo ferric heme-Cu(II) complex from the
      corresponding micro-oxo Fe(III)-Cu(II) species with hydrogen peroxide.
AB  - An oxo-bridged ferric heme-copper(II) complex, obtained by thermal transformation
      of the corresponding peroxo-bridged complex, was reacted with an equimolar amount
      of H2O2 to regenerate the micro-peroxo complex by a ligand exchange from oxo to
      peroxo, without the formation of a ferryl-oxo species or heme degradation as are
      observed in general ferric heme-H2O2 reactions.

PMID- 15719123
TI  - A route to heat resistant solid membranes with performances of liquid
      electrolytes.
AB  - The confinement of ionic liquids within a porous silica matrix was performed by a
      one-step non-hydrolytic sol-gel route, leading to hybrid materials (called
      "ionogels") featuring both the mechanical and transparency properties of silica
      gels and the high ionic conductivity and thermal stability of ionic liquids.

PMID- 15719124
TI  - Polymer-supported nitroxyl radical catalyst for selective aerobic oxidation of
      primary alcohols to aldehydes.
AB  - PS-TEMPO, a polymer-supported 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), was
      successfully applied as a recyclable, active and selective catalyst for the
      oxidation of primary aliphatic and benzylic alcohols to aldehydes by molecular
      oxygen in the presence of Co(NO3)2 and Mn(NO3)2 as co-catalysts.

PMID- 15719125
TI  - A fluorescent assay for chloride transport; identification of a synthetic
      anionophore with improved activity.
AB  - A fluorescent assay based on the chloride-sensitive probe, lucigenin, is
      developed for monitoring chloride transport into vesicles, and used to compare
      the effectiveness of three steroid-derived transporters.

PMID- 15719126
TI  - Selective sensing of Cu(II) at ng ml(-1) level based on phosphorescence quenching
      of 1-bromo-2-methylnaphthalene sandwiched in sodium deoxycholate dimer.
AB  - Using sodium deoxycholate as a protective medium, the selective recognition of
      Cu(II) at ng ml(-1) level is realized through dynamic phosphorescence quenching
      of 1-bromo-2-methylnaphthalene (BMN) without deoxygenation. The limit of
      detection is 4.32 ng ml(-1), and the relative standard deviation is 1% at 10
      microM, linear up to 1 x 10(-5) M.

PMID- 15719127
TI  - Oriented assembly of Au nanorods using biorecognition system.
AB  - The design and formation of a linear assembly of gold nanorods using a
      biomolecular recognition system are described. Anti-mouse IgG was immobilized on
      the {111} end faces of gold nanorods through a thioctic acid containing a
      terminal carboxyl group. The biofunctionalized nanorods can be assembled with the
      desired length using mouse IgG for biorecognition and binding. The gold nanorods
      can be assembled to extended nanorod chains, which can be as long as 3 microm.
      These assembled nanostructures may be used as the precursors for future
      nanodevices.

PMID- 15719128
TI  - Endothelial progenitor cells in angiogenesis.
AB  - Circulating blood contains a subtype of progenitor cells that have the capacity
      to differentiate into mature endothelial cells in vitro and in vivo. These cells
      have been termed endothelial progenitor cells (EPCs). The isolation of EPCs by
      adherence culture or magnetic microbeads has been described. EPCs are
      characterized by the expression of 3 markers, CD133, CD34, and the vascular
      endothelial growth factor receptor-2. After differentiation, EPCs express CD31,
      vascular endothelial cadherin, and von Willebrand factor. Evidence is
      accumulating that EPCs can facilitate endothelial repair and angiogenesis in
      vivo. We observed that EPCs can regenerate damaged endothelial cells in vascular
      grafts in apoE-deficient mice, and that abundant vascular progenitor cells are
      present in the adventitia of the vessel wall. It is not clear yet, however,
      whether these EPCs are essential for these angiogenic and atherogenic processes.
      Moreover, there are still many uncertainties about how cardiovascular risk
      factors alter EPC function. Thus, further studies on the mechanisms of EPC
      homing, releasing and attaching will be of help to explore areas of potential
      basic research and clinical application of EPCs.

PMID- 15719129
TI  - Prevention of isoproterenol-induced tau hyperphosphorylation by melatonin in the
      rat.
AB  - Hyperphosphorylated microtubule-associated protein tau is the major protein
      component of neurofibrillary tangles in the brain of patients with Alzheimer's
      disease (AD). Until now, there is no effective cure to arrest this
      hyperphosphorylation. The present study was designed to explore the in vivo
      preventive effect of melatonin on Alzheimer-like tau hyperphosphorylation.
      Isoproterenol, a beta-receptor agonist, was used to induce tau
      hyperphosphorylation, and for preventive effect of melatonin, the rats were
      injected intraperitoneally with melatonin for 5 d before hippocampi infusion of
      isoproterenol. The level of tau phosphorylation was detected by Western blot and
      immunohistochemistry using sites specific antibodies (PHF-1 and Tau-1), and it
      was normalized by non-phosphorylation dependent total tau antibody (111e). The
      results by Western blot showed that the immunoreaction of tau at PHF-1 epitope
      was enhanced, and the reaction at Tau-1 epitope was weakened significantly at 48
      h after injection of isoproterenol, suggesting hyperphosphorylation of tau at Ser
      396/Ser 404 (PHF-1) and Ser199/Ser 202 (Tau-1) sites. Similar results were
      observed by immunohistochemistry staining, in which hyperphosphorylated tau was
      mainly detected in mossy fibers of hippocampal CA3 region. Pre-injection of rats
      with melatonin intraperitoneally arrested effectively the isoproterenol-induced
      tau hyperphosphorylation at both Tau-1 and PHF-1 sites, implying the preventive
      effect of melatonin in Alzheimer-like tau hyperphosphorylation.

PMID- 15719130
TI  - p38 Mitogen-activated protein kinase mediates hypoxia-induced vascular
      endothelial growth factor release in human endothelial cells.
AB  - Increased vascular endothelial growth factor (VEGF) biosynthesis in vascular
      endothelial cells has been reported to play an obligatory role in promoting
      angiogenesis. Nevertheless, the intracellular signaling mechanisms of hypoxia
      induced VEGF release remain largely unknown. Human umbilical vein endothelial
      cell lines (ECV304) were cultured in normoxic or hypoxic conditions for 12
      approximately 24 h and harvested for determination of VEGF mRNA expression and
      phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (p38 MAPK) by
      real-time reverse transcription polymerase chain reaction (RT-PCR) and Western
      blot analysis, respectively. Secreted VEGF protein was measured by enzyme-linked
      immunosorbent assay (ELISA). It has reported that PD98059, an ERK inhibitor, was
      able to blunt the hypoxia-induced activation of the expression of VEGF gene. In
      accordance with this report, an increase in ERK1/2 phosphorylation and VEGF
      biosynthesis was observed in ECV304 cells cultured in hypoxia, and this increase
      was blocked by PD98059. The novel finding of the present study is that an
      activation of p38 MAPK is involved in hypoxia-induced increase in VEGF
      biosynthesis. SB202190, an inhibitor of p38 MAPK was able to blunt the hypoxia
      induced increase in VEGF biosynthesis. These dada provide the first direct
      evidence for a role of p38 MAPK in mediating hypoxia-induced increase in VEGF
      biosynthesis in human endothelial cells.

PMID- 15719131
TI  - [Voltage-activated potassium channel blockers inhibit anisodamine-induced
      relaxation of rabbit aortic smooth muscles precontracted with noradrenaline].
AB  - Anisodamine, which is originally extracted from scopolia tangutica and is
      currently produced in China, is a tropane alkaloid and a muscarinic cholinoceptor
      blocker. Our previous study found that anisodamine did not alter high K(+)-evoked
      contraction of rabbit aortic rings using isometric tension recording methods, but
      could attenuate noradrenaline (NA)-, histamine- or 5-hydroxytryptamine-induced
      contraction in an endothelium-independent manner. Since the high K(+)-elicited
      depolarization non-selectively inhibits potassium channels in vascular smooth
      muscle cell (VSMC) membrane, the vasodilation effect of some potassium channel
      activators may be inhibited or abolished in high K(+) solution. We hypothesized
      that some potassium channels in VSMC membrane might play a role in the
      anisodamine-induced relaxation of blood vessels. The present experiment was
      designed to investigate whether potassium channel blockers inhibit anisodamine
      induced relaxation of the rabbit isolated aortic rings. In a 8-min period, 1, 3
      and 10 micromol/L of anisodamine, significantly relaxed the 0.01 micromol/L NA
      precontracted aortic ring by (19.1+/-3.1)%, (30.1+/-3.8)% and (38.3+/-4.2)%,
      respectively, compared with the controls [by (4.8+/-2.4)%, (5.1+/-1.8)% and
      (5.6+/-2.5)%, respectively] (P<0.01). 10 mmol/L of CsCl (a non-selective
      potassium channel blocker), 1 mmol/L of 4-aminopyridine [a selective voltage
      activated potassium channel (K(V)) blocker], 10 mumol/L BaCl2 (a selective
      inwardly-rectifying potassium channel blocker), 10 micromol/L of glibenclamide (a
      selective ATP-sensitive potassium channel blocker), 3 micromol/L of charybdotoxin
      (a large- and intermediate-conductance Ca(2+)-activated potassium channels
      blocker) and 3 micromol/L of apamin (a selective small conductance Ca(2+)
      activated potassium channel blocker) significantly increased the NA-induced
      contraction by (14.4+/-3.2)%, (16.3+/-5.8)%, (12.7+/-4.2)%, (13.6+/-2.0)%,
      (11.1+/-5.5)% and (13.4+/-4.3)%, respectively, compared with the control [by (5.6
      +/-1.2)%] (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1 and 3 mmol/L 4
      aminopyridine, anisodamine-induced relaxation of the 0.01 micromol/L NA
      contracted rabbit aortic rings [(28.8+/-3.0)% and (15.9+/-3.7)% or (29.7+/-3.9)%
      and (19.0+/-5.0)%] significantly deceased, compared with that in the absence of
      any potassium channel blocker [(38.3+/-4.2)% (P<0.01)] in a 8-min period.
      However, in the presence of 10, 30 micromol/L of BaCl2, 10, 30 micromol/L of
      glibenclamide, 3 micromol/L of charybdotoxin, or 3 micromol/L apamin, 10
      micromol/L anisodamine-induced relaxation [(37.1+/-3.8)%, (36.2+/-4.7)%, (36.1+/
      2.7)%, (35.6+/-3.3)%, (37.8+/-2.0)% and (39.3 +/-4.7) %, respectively] did not
      decrease, compared with the control [(38.3+/-4.2)%] (P>0.05). This study suggests
      that K(V) blockers inhibit anisodamine-induced relaxation of the rabbit aortic
      smooth muscle precontracted with NA and implies that the K(V) in VSMC membrane
      plays a role in anisodamine-induced relaxation of blood vessels.

PMID- 15719132
TI  - [Changes in voltage-dependent calcium channel currents of vascular smooth muscle
      cells isolated from small mesenteric arteries of simulated weightless rats].
AB  - The aim of the present study was to examine the changes in the function of
      voltage-dependent calcium channels (VDC) of vascular smooth muscle cells (VSMCs)
      isolated from small mesenteric arteries of rats subjected to 1-week or 4-week
      simulated weightlessness. The whole-cell recording mode was used to record
      current densities and Ba(2+) was used as charge carrier. Curves and fitting
      parameters describing steady-state activation and inactivation characteristics of
      VDC were thus obtained. The inward currents recorded from the VSMCs of small
      mesenteric arteries were mainly the Ba(2+) currents through the long-lasting type
      VDC (L-VDC). Compared with that of the control rats, the L-VDC current density of
      VSMCs from small mesenteric arteries showed a trend toward a decrease in the rats
      after 1-week , while a significant decrease was observed in the rats after 4-week
      simulated weightlessness. However, there were no significant differences in the
      opening and closing rates of L-VDCs, the position of steady-state activation and
      inactivation curves, and in the parameters, V(0.5) and k, between either of the
      two groups and its respective control group. The membrane capacitance and the
      reversal potential of the VSMCs from the small mesenteric arteries of rats after
      simulated weightlessness also showed no significant changes. These findings
      suggest that the decreased function of the L-VDC in hindquarter VSMCs might be
      one of the electrophysiological mechanisms that mediate the depressed
      vasoreactivity and atrophic change in hindquarter arteries during adaptation to
      simulated weightlessness in rats.

PMID- 15719133
TI  - Different signal molecules involved in the muscarinic modulation of pacemaker
      current I(f) on the heart of mouse embryo in different developmental stages.
AB  - We isolated mouse embryonic cardiomyocytes derived from timed-pregnant females at
      different periods and used patch-clamp technique to investigate the muscarinic
      cholinergic modulation of pacemaker current I(f) in different developmental
      stages. In early development stage (EDS), muscarinic agonist carbachol (CCh)
      significantly decreased the magnitude of the pacemaker current I(f) but had no
      effect in late development stage (LDS). Forskolin (a direct adenylate cyclase
      activator) and IBMX (a non-selective phosphodiesterase inhibitor) increased I(f)
      in both EDS and LDS cells. Interestingly, although both forskolin and IBMX
      increased basal I(f), their effects on CCh-inhibited I(f) were different.
      Forskolin did not reverse the inhibitory action of CCh until intermediate
      development stage (IDS). In contrast, IBMX reversed the inhibitory action of CCh
      on I(f) in EDS but not in IDS. It is suggested that a decrease in intracellular
      cAMP is a possible mechanism for CCh to modulate I(f). During the EDS and IDS CCh
      controls the cytoplasmic cAMP level by different pathways: In EDS, CCh modulates
      I(f) possibly by activating PDE which accelerates the breakdown of cAMP, but in
      IDS possibly by inhibiting adenylate cyclase (AC) which then reduces the
      synthesis of cAMP.

PMID- 15719134
TI  - Effect of inducible nitric oxide synthase on intestinal microcirculation in
      endotoxic shock.
AB  - To investigate the changes of intestinal microcirculation in endotoxic shock and
      the effect of inducible nitric oxide synthase (iNOS) on intestinal
      microcirculation, endotoxic shock was induced by intravenous injection of
      lipopolysaccharide (LPS) in mice. Mean arterial pressure (MAP) was monitored
      throughout the experimental procedure. The velocity and flux of red blood cell
      (RBC) in villus tip arteriole and capillaries were measured by FITC-labeled
      erythrocytes and intravital microscopy. The effect of iNOS was determined by
      targeted disruption of mice iNOS-gene and administration of S-methylthiourea
      sulfate (SMT), a selective inhibitor of iNOS, before LPS injection. No
      significant differences in MAP, RBC velocity and flux at baseline were found
      among wild type mice, SMT pretreated mice and iNOS-gene knockout mice. LPS
      induced a dramatic fall of MAP in wild type mice. The decrease of MAP was
      significantly restored in iNOS-gene knockout mice and in wild type mice received
      SMT before LPS injection. The velocity and flux of RBC in villus tip arteriole
      and capillaries decreased markedly after LPS injection in wild type mice, while
      significantly higher velocity and flux of RBC were found in iNOS-gene knockout
      mice and SMT-pretreated mice both 60 and 120 min after LPS injection. The results
      demonstrate that iNOS plays an essential role in the intestinal microcirculation
      disturbance which occurs in endotoxic shock.

PMID- 15719135
TI  - [Effects of nitric oxide on peritoneal lymphatic stomata and lymph drainage via
      NO-cGMP-Ca2+ pathway].
AB  - To study the cell signal transduction mechanism of nitric oxide (NO) on the
      peritoneal lymphatic stomata and lymph drainage in the rat, cGMP content were
      measured by a commercially available radioimmunoassay kit, and the [Ca(2+)](i)
      were observed by a confocal laser scanning microscope in the cultured peritoneal
      mesothelial cell. Animal experiment was practiced to study the effect of NO-cGMP
      Ca(2+) pathway on the lymphatic stomata and lymph absorption. The results showed
      that: (1) Sper/NO increased cGMP of the rat peritoneal mesothelial cell (RPMC) in
      a dose-dependent manner (P<0.01) compared to the control group. This effect was
      blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) (P<0.05), a
      specific inhibitor of soluble guanylyl cyclase (sGC). The level of [Ca(2+)](i) in
      single RPMC decreased by adding Sper/NO (P<0.05). Pretreatment with ODQ for 10
      min blocked the Sper/NO-induced decrease in [Ca(2+)](i). L-typed calcium channel
      blocker nifedipine induced an immediate and marked decrease in [Ca(2+)](i)
      (P<0.05).. After [Ca(2+)](i) reached a balance again, adding Sper/NO could not
      change [Ca(2+)](i) (P>0.05). (2) Sper/NO increased the area of the stomata
      (P<0.01) and the quantity of the tracer in a dose-dependent manner (P<0.05)
      compared to the control group. Pretreatment with ODQ significantly inhibited
      Sper/NO-induced change of lymphatic stomata and lymph drainage (P<0.01).
      Nifedipine increased the opening area of the lymphatic stomata (P< 0.01) and the
      concentration of absorbed trypan blue of the diaphragm (P<0.05). Sper/NO could
      not make a further change in the samples pretreated by nifedipine (P> 0.05). The
      results indicate that NO can decrease [Ca(2+)](i) in the RPMC through the NO-cGMP
      pathway. This procession is related with the L- type voltage-gated Ca(2+)
      channel. NO enlarges the opening area of the lymphatic stomata and enhances the
      lymph drainage of tracer by NO-cGMP-[Ca(2+)](i) pathway.

PMID- 15719136
TI  - [The changes of bcl-2, bax expression and neuron apoptosis in the hippocampus
      after the blockade of cervical lymphatics of rats].
AB  - To investigate the changes in bcl-2, bax expression and neuron apoptosis in the
      hippocampus after the blockade of cervical lymphatics, the model of lymphostatic
      encephalopathy was established by occluding and removing both the superficial and
      deep cervical lymph nodes in rats. The animals were sacrificed at 1, 2, 3, 5, 7
      and 14 d after operation. H and E staining was used to observe the structure of
      brain tissues and TUNEL staining was used to detect in situ cell apoptosis in the
      hippocampus. The expression of bcl-2 and bax in the hippocampus were examined by
      RT-PCR. The results showed that cerebroedema appeared at day 2 and was most
      serious at day 5 after the blockade of cervical lymphatics. The number of TUNEL
      positive cells began to increase at day 2 and reached the maximum at day 5. The
      expression of bax began to increase at day 1 and reached the maximum at day 2.
      The expression of bcl-2 began to decrease at day 1 and dropped to the minimum at
      day 5. The items mentioned above recovered to control level at day 14. These
      results suggest that lymphostatic encephalopathy following the blockade of
      cervical lymphatics result in changes in bcl-2 and bax expression in the
      hippocampus and that apoptosis is the main form of neuron death.

PMID- 15719137
TI  - Dynamic modulations on intensity sensitivity evoked by weak noise in the inferior
      collicular neurons.
AB  - In order to explore the possible mechanisms by which ethologically relevant
      sounds can be extracted from complex auditory environments, this study examined
      the effects of weak noise on the rate-intensity functions (RIFs) of neurons
      responding to tone burst in the inferior colliculus (IC) of nine mice (Mus
      musculus Km). Under free field stimuli conditions, a total of 112 IC neurons were
      recorded. RIFs with and without simultaneous presentation of weak noise, of which
      the intensity was relative to 5 dB below minimum threshold of tone burst, were
      measured in 44 IC neurons. By means of evaluating the changes of dynamic range
      (DR), slope of RIFs, and percent inhibition at different tone burst intensities
      evoked by the weak noise, three types of variations in RIFs were observed, i. e.,
      inhibition (39/44, 88.6%), facilitation (2/44, 4.6%), and no effectiveness (3/44,
      6.8%). Statistical analysis indicated that only inhibitory effect of weak noise
      was significant (P< 0.001, n = 39). The inhibitory effect of weak noise was
      greater at lower stimulus intensity of tone burst but decreased significantly
      with increased stimulus intensity (P< 0.0001, n = 39). In addition, the DR and
      slope of RIFs became narrower and steeper with weak noise presentation,
      respectively (P< 0.01, n = 31). The results from the present study suggest that
      weak noise exerts a dynamic modulatory action on acoustical intensity sensitivity
      of IC neurons, which possibly leads to a better understanding of neural
      mechanisms underlying the extraction of sound signals from natural auditory
      scenes.

PMID- 15719138
TI  - [Influence of glutamate and NMDA-receptor antagonist MK-801 on the electric
      activities of pain-excitation neurons in the nucleus accumbens of rats].
AB  - The experiment explored the influence of glutamic acid (Glu) and the NMDA
      receptor antagonist dizocilpine maleate (MK-801) on the pain-evoked responses of
      pain-excitation neurons (PEN) in the nucleus accumbens (NAc) of rats. The trains
      of electric impulses applied to the sciatic nerve were used as noxious
      stimulation. The discharges of PEN in NAc were recorded by glass microelectrode.
      We observed the influence of intracerebroventricular (icv) injection of Glu and
      microinjection of MK-801 into the NAc on the noxious stimulation-evoked
      activities of PEN in NAc. The results showed that the noxious stimulation
      potentiated the electric activities of PEN in NAc. Intracerebroventricular
      injection of Glu (10 nmol/10 microl) increased the frequency of the discharge of
      PEN evoked by the noxious stimulation in NAc, the Glu-induced response was
      blocked by the injection of MK-801 (1.0 nmol/0.5 microl) into NAc. MK-801 partly
      inhibited the response of PEN upon the noxious stimulation. It is therefore
      suggested that the facilitatory effect of Glu on PEN response in NAc to the
      noxious stimulation is mediated by NMDA receptors, and that Glu and NMDA
      receptors are involved in the modulation of nociceptive information transmission
      in the NAc.

PMID- 15719139
TI  - Effects of glutamate and MK-801 on the metabolism of dopamine in the striatum of
      normal and parkinsonian rats.
AB  - The direct effects of glutamate and dizocilpine maleate (MK-801, non-competitive
      N-Methyl-D-aspartate glutamate receptor antagonist) on the metabolism of dopamine
      were investigated in the striatum of normal and parkinsonian rats. L-dopa, L
      glutamic acid and MK-801 were administered in the striatum locally by
      microdialysis. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      were simultaneously sampled by microdialysis. The concentrations of DOPAC and HVA
      were assayed by high performance liquid chromatography with electrochemical
      detection (HPLC-ECD). L-dopa increased the concentrations of DOPAC and HVA in the
      striatum of normal and parkinsonian rats. L-glutamic acid decreased the
      concentrations of DOPAC and HVA in striatum of normal rats but not parkinsonian
      rats. MK-801 increased the concentrations of DOPAC and HVA in the striatum of
      normal rats but not parkinsonian rats. MK-801 prevented the L-glutamic acid
      induced decrease of DOPAC and HVA in the striatum of normal rats. Our results
      indicate that glutamate modulates the metabolism of dopamine (DA) through NMDA
      receptors and that the improvement of PD by MK-801 is not through improving the
      metabolism of DA.

PMID- 15719140
TI  - Changes of synaptic structure after long-lasting LTP induced by high and low
      frequency tetanus in slices of the rat visual cortex.
AB  - Synaptic ultrastructural changes after long-lasting long-term potentiation (L
      LTP) induced by 2 and 100 Hz tetanus were investigated by electron microscopic
      and stereological approach in slices of the developing rat visual cortex
      (postnatal days 15~21). Both 2 and 100 Hz tetanus-induced L-LTP groups showed
      significant increases in synaptic interface curvature, synaptic numeric density
      and postsynaptic density thickness, as well as significant decreases in the cleft
      width, as compared with the control groups. In addition, the volume density of
      the active zone (AZ) was increased significantly in the 100 Hz tetanus-induced L
      LTP group, but not in the 2 Hz group. The mean lateral area of individual AZ in
      the 100 Hz group was relatively higher than that in the 2 Hz group. These data
      suggest that newly formed synapses in the 100 Hz tetanus-induced L-LTP group are
      larger than those in the 2 Hz group and that 100 Hz tetanus might trigger
      reorganization or synthesis of postsynaptic cytoskeleton.

PMID- 15719141
TI  - [Increased subthalamic neuronal activity after dorsal raphe nucleus lesion by 5,7
      dihydroxytryptamine in the rat].
AB  - In vivo extracellular recordings were made in the subthalamic nucleus (STN) of
      intact control rats and rats with 5,7-dihydroxytryptamine (5,7-DHT) -produced
      lesion of dorsal raphe nucleus (DRN). The results showed that the firing rate of
      STN neurons in control rats and DRN-lesioned rats were (6.93+/-6.55) Hz and
      (11.27+/-9.31) Hz, respectively, and the firing rate of DRN-lesioned rats
      significantly increased when compared to the control rats (P<0.01). In control
      rats, 13% of STN neurons discharged regularly, 46% irregularly and 41% in bursts.
      In DRN-lesioned rats, 9% of STN neurons discharged regularly, 14% irregularly and
      77% in bursts, the percentage of STN neurons firing in bursts was obviously
      higher than that of the control rats (P<0.01). In addition, the mean interspike
      interval coefficient of variation of STN neurons in control rats and DRN-lesioned
      rats were (0.05+/-0.04) and (0.11+/-0.09), respectively. The mean interspike
      interval coefficient of variation of DRN-lesioned rats was significantly higher
      than that of the control rats (P<0.001). These results show that the firing rate
      and the bursting pattern rate of neurons in STN of DRN-lesioned rats increase
      significantly, suggesting that DRN inhibits the neuronal activity of the
      subthalamic neurons in the intact rat.

PMID- 15719142
TI  - Adenosine A1 receptors are involved in the modulation of the rhythmical
      respiration in neonatal rat brainstem slice in vitro.
AB  - This study was designed to investigate whether adenosine A1 receptors could
      modulate primary rhythmical respiration in mammals. Experiments were performed in
      in vitro brainstem slice preparations from neonatal rats. These preparations
      included the medial region of the nucleus retrofacialis (mNRF) with the
      hypoglossal nerve rootlets retained. The activity of the inspiration-related
      neurons (I neurons) in mNRF and respiratory rhythmical discharge activity (RRDA)
      of the hypoglossal nerve rootlets were simultaneously recorded by using
      microelectrodes and suction electrodes, respectively. Possible roles of adenosine
      A1 receptors in rhythmical respiration were investigated by administration of
      adenosine A1 receptor agonist R-phenylisopropyl-adenosine (R-PIA) and its
      specific antagonist 8-cyclopentyl-1,3- dipropylxanthine (DPCPX) into a modified
      Kreb's perfusion solution (MKS). DPCPX induced a significant decrease in the
      expiratory time and the respiratory cycles, and an increase in the discharge
      frequency and peak frequency of I neurons in the middle phase of inspiration.
      However, R-PIA significantly decreased the inspiratory time and integral
      amplitude as well as prolonged respiratory cycle. Moreover, the discharge
      frequency and the peak frequency of I neurons were decreased in the middle phase
      of inspiration, but not in the initial and terminal phases. The effect of R-PIA
      on rhythmical discharges could be partially reversed by additional application of
      DPCPX. These results indicate that adenosine A1-receptors are possibly involved
      in the modulation of rhythmical respiration through the inhibitory synaptic input
      from I neurons.

PMID- 15719143
TI  - [Circadian rhythms and light responses of clock gene and arylalkylamine N
      acetyltransferase gene expressions in the pineal gland of rats].
AB  - This study was to investigate the circadian rhythms and light responses of Clock
      gene and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat
      pineal gland under the 12 h-light : 12 h-dark cycle condition (LD) and constant
      darkness (DD). Sprague-Dawley rats housed under the light regime of LD (n=36) for
      4 weeks and of DD (n=36) for 8 weeks were sampled for the pineal gland once a
      group (n=6) every 4 h in a circadian day. The total RNA was extracted from each
      sample and the semiquantitative reverse transcription polymerase chain reaction
      (RT-PCR) was used to determine the temporal changes in mRNA levels of Clock and
      NAT genes during different circadian times or zeitgeber times. The data were
      analysed by the cosine function software, Clock Lab software and the amplitude F
      test was used to reveal the circadian rhythm. The main results obtained are as
      follows. (1) In DD or LD condition, both of Clock and NAT genes mRNA levels in
      the pineal gland showed robust circadian oscillation (P< 0.05) with the peak at
      the subjective night or at night-time. (2) In comparison with DD regime, the
      amplitudes and the mRNA levels at peaks of Clock and NAT genes expressions in LD
      in the pineal gland were significantly reduced (P< 0.05). (3) In DD or LD
      condition, the circadian expressions of NAT gene were similar in pattern to those
      of Clock gene in the pineal gland (P> 0.05). These findings suggest that the
      expressions of Clock and NAT genes in the pineal gland not only show remarkably
      synchronous endogenous circadian rhythmic changes, but also response to the
      ambient light signal in a reduced manner.

PMID- 15719144
TI  - Ahimsa and alternatives -- the concept of the 4th R. The CPCSEA in India.
AB  - The Committee for the Purpose of Control and Supervision of Experiments on
      Animals (CPCSEA) in India is one of a kind in the world. It is a statutory body
      of the government of India formed by an act of the Indian parliament. This body
      consists of nominated members and representatives from national regulatory
      agencies, Ministry of Health and Family Welfare, Ministry of Environment and
      Forests, national academic and research councils, premier research institutes,
      eminent scientists and animal welfare organisations. The CPCSEA draws its powers
      from the Prevention of Cruelty to Animals (PCA) Act of 1960 which states that the
      duty of the committee is "to take all such measures as may be necessary to ensure
      that animals are not subject to unnecessary pain or suffering before, during or
      after the performance of experiments on them". With the power to promulgate its
      own laws to ensure the humane and ethical use of animals in research and
      education, the CPCSEA in 1998 notified in the gazette of India the "Breeding of
      and Experiments on Animals (Control and Supervision) Rules 1998". The CPCSEA is
      unique in that the law in itself has enabled the creation of a common platform of
      discussion for scientists and animal activists for humane and progressive
      solutions for the use of animals in experimentation. In a country that is caught
      in a paradox of violence and rich cultural and religious traditions, India still
      draws a lot of its power from the concept of "Ahimsa" (the philosophy of non
      violence). This concept is also pertinent to the use of animals in laboratories.
      Unethical, inhumane and unscientific practices, and ignorance of the use of
      alternatives were the way of science until 1999 when CPCSEA became functional.
      For four years CPCSEA has waged a battle, rescued thousands of animals from
      laboratories, fought legal battles to victory, enforced for the first time in the
      country good laboratory practice, designed guidelines for the use of animals in
      the production of immunobiologicals, introduced the credo of 3R principles,
      trained and taught scientific personnel the credibility of humane science and
      most importantly brought forward the concept of the fourth R, "rehabilitation" of
      used laboratory animals. Today CPCSEA has made it a national policy that
      personnel using experimental animals have a moral responsibility towards these
      animals after their use. Costs of after-care/rehabilitation of animals post
      experimentation are to be a part of research costs and should be scaled in
      positive correlation with the level of sentience of the animals. This paper is
      about the Indian law on animal experimentation and the success story of the
      CPCSEA in India in inculcating the credo of 4Rs -- Replacement, Reduction,
      Refinement, and Rehabilitation of animals used in experimentation.

PMID- 15719146
TI  - Use of nonhuman primates in research in Sweden: 25 year longitudinal survey.
AB  - All scientific studies published in journals in which research was performed on
      nonhuman primates in Sweden between 1979 and 2003 (N=1038) were identified and
      sampled according to species used, area of research, research class and
      geographic location. Results showed that nonhuman primates were used in various
      scientific disciplines and that the number of articles published peaked in the
      early 1990s. Macaca fascicularis and M. mulatta were the most commonly used
      species. During the sample period projects related to genetics, HIV, and
      neuroscience increased, whereas projects related to dentistry, ophthalmology and
      physiology seem to have disappeared.

PMID- 15719145
TI  - [Whereabouts of surplus and surviving laboratory animals].
AB  - Most research and breeding institutions have to deal with the problem of post
      experimental or surplus laboratory animals. The German law on Animal Welfare
      (Tierschutzgesetz) forbids to kill animals without proper reason. This
      prohibition is valid for laboratory animals, too. If an animal survives an
      experiment without permanent pain or harm, the further remain must be organised.
      Re-homing of these animals to private people is one solution for this problem.
      The animals can be passed on to a family as a pet. Another possibility is to re
      home the animal with the help of a welfare organisation. This way offers some
      advantages. The organisation seeks the new owners, gives them all necessary
      information and remain available for them. Using such an organisation, the re
      homing process is to a great extend safe and anonymous for the research
      institution. Many institutions already made very good experiences in the
      cooperation with welfare organisations.

PMID- 15719147
TI  - Animal vs. non-animal tests for the monitoring of marine biotoxins in the EU.
AB  - Since bivalve molluscs can contain algae biotoxins that can cause
      gastroenterological or even lethal neurological diseases in humans, a public
      health control system on marine biotoxins has been implemented in EU Directive
      91/492. Currently, the reference method laid down for this purpose is the so
      called "mouse bioassay" with death of the animals as an endpoint. To date, this
      extremely distressful animal test has not been standardised or validated, and
      there is scientific evidence that it is neither relevant nor reliable. Therefore
      different EU Member States have been striving to replace the mouse bioassay or to
      reduce the animal numbers and the distress for the animals. In the United
      Kingdom, the test is being performed with two instead of three mice, the animals
      are anaesthetised before injection of the mollusc extract and remain in narcosis
      until their death. In Germany the mouse bioassay has not been performed for many
      years; without restriction of consumer health safety, marine biotoxins are
      detected with chemical analytical test methods. The application of alternative
      test methods is legally required according to EU Directive 86/609 on the
      Protection of Laboratory Animals. Apparently there is a conflict between two
      equal valid EU Directives, which has to be overcome.

PMID- 15719148
TI  - High interleukin 12 and low interleukin 10 production after in vitro stimulation
      detected in sepsis survivors.
AB  - OBJECTIVE: To evaluate viability of isolated peripheral blood mononuclear cells
      (PBMC) and production of cytokines in vitro after stimulation as prognostic
      factors for survival in sepsis patients. DESIGN: Prospective study of the
      biological response of PBMC in the onset of severe sepsis. SETTING: Research
      laboratory of molecular biology and immunology and university hospital ICU,
      Faculty of Medicine, Trakia University. PATIENTS: Twenty-three patients meeting
      the criteria for severe sepsis, and 14 control subjects. INTERVENTIONS: Isolated
      PBMC were stimulated in vitro with: C3-binding glycoprotein (C3bgp; 30 microg),
      lipopolysaccharide (30 microg), phytohemagglutinin (20 microg), pokeweed mitogen
      (30 microg), and dexamethasone (500 microg). MEASUREMENTS AND RESULTS: We
      measured the levels of interleukins (IL) 6, 10, and 12 in culture supernatants.
      Stimulation with C3bgp and phytohemagglutinin led to significantly lower PBMC
      secretion of IL-6 in nonsurvivors than in survivors and healthy donors.
      Stimulation with C3bgp, lipopolysaccharide, and pokeweed mitogen considerably
      reduced IL-12 production in nonsurvivors. Stimulation with lipopolysaccharide and
      pokeweed mitogen caused immune cells in nonsurvivors to produce higher levels of
      IL-10 than in survivors. Survival of PBMC reduced viability for nonsurvivors'
      PBMC, both spontaneously and as induced by lipopolysaccharide or pokeweed
      mitogen. CONCLUSIONS: The viability of PBMC at the onset of sepsis and enhanced
      production of IL-12 and diminished production of IL-10 after stimulation with all
      stimuli used may be a favorable prognostic factor in sepsis.

PMID- 15719150
TI  - Pressure, flow and Occam's Razor: a matter of "steal"?

PMID- 15719151
TI  - Systemic sclerosis, pulmonary fibrosis and anti-MPO antibodies.

PMID- 15719149
TI  - Year in review in intensive care medicine, 2004. III. Outcome, ICU organisation,
      scoring, quality of life, ethics, psychological problems and communication in the
      ICU, immunity and hemodynamics during sepsis, pediatric and neonatal critical
      care, experimental studies.

PMID- 15719153
TI  - Comparison of quantitative ultrasound of the phalanges with conventional bone
      densitometry in healthy postmenopausal women.
AB  - The objective of this study was to evaluate the utility of the quantitative
      ultrasound (QUS) technique for the identification of subjects with spine fracture
      or low bone mineral density (BMD) previously determined by dual energy X-ray
      absorptiometry (DEXA). QUS of the phalanges in 1,350 postmenopausal women (60-83
      years old) was compared with DEXA measurements of four skeletal sites (lumbar
      spine, total hip, femoral neck, and distal radius) of the same subjects. The
      contribution of body mass index (BMI) was also assessed. Amplitude dependent
      speed of sound (AD-SoS), ultrasound bone profile index (UBPI), and BMD of all
      anatomical regions, except for the spine, decreased significantly with increasing
      age quartiles. QUS parameters correlated weakly but significantly with BMD ( r
      =0.21-0.31, p <0.01). After adjustment for BMI, the association between QUS
      parameters and BMD remained unchanged. UBPI was found to be independent of BMI.
      All techniques and all sites were able to significantly discriminate fractured
      from non-fractured subjects by receiver operating characteristic (ROC) analysis
      (area under the curve [AUC]> or =0.60, p <0.0001). AD-SoS and UBPI showed similar
      fracture discrimination ability of spine, distal radius and total body BMD in
      terms of odds ratios, but BMD of the total hip and femoral neck showed the best
      performance in discriminating fractured from non-fractured subjects. In
      conclusion, QUS assessment of the phalanges correlates moderately with BMD of all
      skeletal sites and is able to effectively discriminate fractured from non
      fractured subjects.

PMID- 15719152
TI  - Evaluation of hip fracture risk in relation to fall direction.
AB  - The purpose of this study is to evaluate hip fracture risk in relation to fall
      direction, and to elucidate factors that influence the impact force in falls on
      the hip. Eight healthy volunteers performed deliberate falls in three directions
      (lateral, posterolateral and posterior) on a force platform covered by a mattress
      of 13 cm thickness. Fall descent motions and impact postures were examined by a
      three-dimensional analyzer. The maximum ground force reaction, velocity of the
      greater trochanter at impact, and activity of quadriceps and gluteus medius were
      measured. In all trials of lateral and posterolateral falls, but not of posterior
      falls, the subjects hit their greater trochanter directly on the mattress. The
      impact forces were between 2,000 N and 4,000 N. Posterolateral falls showed
      significantly higher velocity at impact than did posterior falls. The height and
      the lower limb length exhibited positive correlations with the impact force in
      all directions of fall. In the lateral fall, there was a positive correlation
      between the activity of quadriceps and the impact force. In view of the impact
      point, force, and velocity, the posterolateral fall seemed to carry the highest
      risk of hip fracture.

PMID- 15719154
TI  - Association studies of the adenosine A2a receptor (1976T > C) genetic
      polymorphism in Parkinson's disease and schizophrenia.
AB  - Given the implications with respect to the pathogenesis of dopaminergic
      dysfunction in schizophrenia and Parkinson's disease (PD), as well as the
      reciprocal antagonistic interactions between adenosine A2a receptor (A2aAR) and
      the dopamine D2 receptors, A2aAR may be a candidate gene conferring
      susceptibility to PD or schizophrenia. In this study, we tested the hypothesis
      that the A2aAR 1976T > C genetic variant confers susceptibility to or is related
      to the onset age of schizophrenia or PD using a sample population consisting of
      94 PD and 227 schizophrenic patients. We also tested whether the A2aAR 1976T > C
      relates to antipsychotic-induced tardive dyskinesia in the schizophrenic
      population. The results demonstrated that in comparing PD patients and controls
      the distribution of the A2aAR 1976T > C genotypes (P=0.788) and alleles (P=0.702)
      did not vary significantly. Furthermore, the PD onset age was not significantly
      different amongst the three A2aAR 1976T > C genotypic groups. In comparing
      schizophrenic patients and controls, the distribution of the A2aAR genotypes
      (P=0.330) and alleles (P=0.632) also did not differ significantly. The onset age
      of schizophrenia and tardive dyskinesia (evaluated with Abnormal Involuntary
      Movements Scale) were similar within the three A2aAR genotypic groups. Our
      findings suggest that it is unlikely that the A2aAR 1976T > C polymorphism plays
      a major role in the pathogenesis of PD, schizophrenia, or antipsychotic-induced
      tardive dyskinesia in the Chinese population.

PMID- 15719155
TI  - Formalin hindpaw injection induces changes in the [3H]prazosin binding to alpha1
      adrenoceptors in specific regions of the mouse brain and spinal cord.
AB  - Involvement of the alpha1-adrenoceptor subtypes in early and late phases of
      formalin pain was investigated by quantitative in vitro autoradiography in the
      spinal cord and brain structures of CD-1 mice. Total alpha1-adrenoceptors binding
      (including all alpha1-adrenoceptor subtypes) was assessed with [3H]prazosin;
      alpha(1B)-adrenoceptor was assessed with [3H]prazosin in the presence of 10 nM
      WB4101 to mask remaining alpha1-adrenoceptor subtypes. Early after formalin
      injection the alpha1-adrenoceptors (mainly alpha1B receptor) binding was reduced
      in the contralateral hind limb area of the somatosensory cortex and in the
      secondary motor cortex. A reduction occurred also in the ipsilateral laminae I
      III of the spinal cord (both alpha1B- and non-alpha1B-adrenoceptors). Lately an
      increase of alpha1-adrenoceptors binding (mostly subtypes other than alpha1B)
      appeared in discrete amygdaloid and thalamic nuclei. These results provide the
      first description of changes at the level of central alpha1-adrenoceptors'
      binding during the formalin-induced pain in mice. Their distribution suggests
      that they may have a functional meaning.

PMID- 15719156
TI  - Imaging of dopamine transporters and D2 receptors in vascular parkinsonism: a
      report of four cases.
AB  - The role of nuclear medicine imaging in the diagnosis of vascular parkinsonism
      (VP) has been addressed by only few studies up to now. Most previous reports
      suggest no or only mild impairment of DAT and D2 receptors in VP. In contrast, in
      four patients with VP, reported here, the combined DAT and D2 receptor SPECT
      showed highly unusual changes in the pre- and/or postsynaptic dopaminergic
      system. The possible value of combined DAT/D2 receptor SPECT imaging should be
      investigated by future prospective studies.

PMID- 15719158
TI  - Heavy metals in soils and crops in Southeast Asia. 1. Peninsular Malaysia.
AB  - In a reconnaisance soil geochemical and plant survey undertaken to study the
      heavy metal uptake by major food crops in Malaysia, 241 soils were analysed for
      cation exchange capacity (CEC), organic carbon (C), pH, electrical conductivity
      (EC) and available phosphorus (P) using appropriate procedures. These soils were
      also analysed for arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper
      (Cu), mercury (Hg), nickel (Ni), lead (Pb) and zinc (Zn) using aqua regia
      digestion, together with 180 plant samples using nitric acid digestion.
      Regression analysis between the edible plant part and aqua regia soluble soil As,
      Cd, Cr, Cu, Hg, Ni, Pb and Zn concentrations sampled throughout Peninsular
      Malaysia, indicated a positive relationship for Pb in all the plants sampled in
      the survey (R2 = 0.195, p < 0.001), for Ni in corn (R2 = 0.649, p < 0.005), for
      Cu in chili (R2 = 0.344, p < 0.010) and for Zn in chili (R2 = 0.501, p < 0.001).
      Principal component analysis of the soil data suggested that concentrations of
      Co, Ni, Pb and Zn were strongly correlated with concentrations of Al and Fe,
      which is suggestive of evidence of background variations due to changes in soil
      mineralogy. Thus the evidence for widespread contamination of soils by these
      elements through agricultural activities is not strong. Chromium was correlated
      with soil pH and EC, Na, S, and Ca while Hg was not correlated with any of these
      components, suggesting diffuse pollution by aerial deposition. However As, Cd, Cu
      were strongly associated with organic matter and available and aqua regia soluble
      soil P, which we attribute to inputs in agricultural fertilisers and soil organic
      amendments (e.g. manures, composts).

PMID- 15719157
TI  - Increased immune response in mice consuming rice bran oil.
AB  - BACKGROUND: Polyunsaturated fatty acids play a key role in a number of biological
      functions. Rice bran oil (RBO) is rich in linoleic acid, an essential n-6 fatty
      acid. n-6 fatty acids are said to have proinflammatory effects as a result of an
      increase in n-6 fatty acid-derived eicosanoids. RBO is also rich in gamma
      oryzanol, a compound from the unsaponifiable fraction, with antioxidant
      properties. OBJECTIVE: The aim of this work is to examine the effect of RBO
      and/or gamma-oryzanol-enriched diets on the regulation of the immune response.
      METHODS: 4 week-old Balb/C mice were fed diets enriched with either RBO or high
      oleic-sunflower oil (HOSO), for one month. Serum samples, bone marrow-derived
      macrophages and lymphocytes from the spleen were collected. RESULTS: Compared to
      HOSO, our results show that RBO modulates the immune system by enhancing B
      lymphocyte proliferation (6842 +/- 2959 vs 10073 +/- 4186 cpm; HOSO vs RBO; n =
      10 per group) and TH1-type cytokines such as IL-2 (55.85 +/- 18.2 vs 101.7 +/-
      21.6 pg/ml) or TNF-alpha (49.12 +/- 18.6 vs 184.9 +/- 46.2 pg/ml; HOSO vs RBO) in
      a significant way (n = 10 per group). Moreover, the reduction found in the TH2
      cytokine IL-4 (7.59 +/- 2.3 vs 4.48 +/- 1.6 pg/ml) and IgE (56.9 +/- 39.2 vs 42.4
      +/- 35.2 ng/ ml; HOSO vs RBO, n = 10 per group) levels suggests RBO may have
      antiallergenic properties. To elucidate the role of gamma-oryzanol, a similar
      study was also carried out including diets enriched with refined RBO or HOSO
      containing gamma-oryzanol (2 %). Our results suggest that although gamma-oryzanol
      may modulate the immune system, it is not responsible for the overall
      immunostimulation effect seen for RBO. CONCLUSIONS: RBO-enriched diets could be
      useful in situations where a potentiation of the immune response was required.
      The fatty acids composition, more than the unsaponifiable fraction, might be
      responsible for this effect.

PMID- 15719159
TI  - Heavy metals in soils and crops in Southeast Asia. 2. Thailand.
AB  - A reconnaissance soil geochemical and concomitant plant survey based on 318 soil
      (0-15 cm) and 122 plant samples was used for the assessment of heavy metal
      pollution of agricultural soils and crops of Thailand. Arsenic (As), cadmium
      (Cd), cobalt (Co), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), lead
      (Pb) and zinc (Zn) were determined in soils using aqua regia digestion, and in
      plants using nitric acid digestion. Organic carbon (C), pH, electrical
      conductivity (EC) and available phosphorus (P) were determined on the soil
      samples using appropriate procedures. Results indicated that concentrations of
      heavy metals varied widely among the different regions of Thailand. Regression
      analysis between the concentrations of metals in soil (aqua regia extractable)
      and edible plant parts indicated a small but positive relationship for Cd in all
      the plants sampled in the survey (R2 = 0.081, p < 0.001). There was also a
      positive relationship between soil and plant Cd concentrations in rice (R2 =
      0.242, p < 0.010), and negative relationships for Zn in rice (R2 = 0.385, p <
      0.001), and Cu (R2 = 0.355, p < 0.001) and Zn (R2 = 0.122, p < 0.026) in
      glutinous rice. Principal component analysis of the soil data suggested that
      concentrations of As, Co, Cr, Cu, Hg, Ni and Pb were strongly correlated with
      concentrations of Al and Fe, which is suggestive of evidence of background
      variations due to changes in soil mineralogy. Thus, the evidence for widespread
      contamination of soils by these elements through agricultural activities is not
      strong. On the other hand, Cd and Zn were strongly correlated with organic matter
      and concentrations of available and aqua regia extractable P. This is attributed
      to input of contaminants in agricultural fertilisers and soil amendments (e.g.
      manures, composts).

PMID- 15719160
TI  - A case study of spatial variation and enrichment of selected elements in ambient
      particulate matter around a large coal-fired power station in central India.
AB  - The dominant use of coal in power sectors has been associated with adverse
      environmental impacts. Ambient air monitoring for the two size fractions of
      particulate matter, respirable suspended particulate matter (RSPM) and non
      respirable suspended particulate matter (NRSPM) in the downwind and upwind
      directions of a large coal-fired power station in central India, was carried out.
      Collected samples of ambient particulate matter were analysed atomic absorption
      spectrophotometrically for 15 elements. Spatial variability in elemental
      composition of RSPM and NRSPM and the degree of enrichment of these toxic metals
      in RSPM were investigated. A significant spatial variability for the elements in
      RSPM and NRSPM and higher degrees of enrichment of the elements were observed.

PMID- 15719161
TI  - Impact of mining activities on soils in a semi-arid environment: Sierra Almagrera
      district, SE Spain.
AB  - Field and laboratory-column studies were undertaken in order to investigate soil
      contamination derived from past mining activity in the Sierra Almagrera (SA)
      district in southeast Spain. The tailings, soil and sediment samples that were
      collected showed high concentrations of Ag, As, Ba, Cu, Pb, Sb and Zn when
      analyzed. The mean concentrations of these elements in the tailings were 29.8,
      285.4, 54000, 57.7, 2687.5, 179.0 and 2269.0 ppm, respectively. In the soil
      samples these decreased to 14.3, 96.9, 24700, 37.5, 1859.1, 168.5 and 815.7 ppm,
      respectively. Geochemical analyses demonstrated high levels of As, Pb and Zn
      which were above the intervention values set forth in the Andalusian Regulations
      for Contaminated Soils for As (>50 ppm), Pb (>500 ppm) and Zn (>2000 ppm). Column
      experiments and mineralogical studies suggest that the dissolution of sulfates
      and other secondary phases, accumulated in soils and waste-sites during the dry
      season, acts to control the mobility of metals. The elution curves obtained from
      column experiments showed a mobilization of Ba, Cu, Pb and Zn, while a low
      mobility was seen for Ag, As and Sb.

PMID- 15719162
TI  - Goitre and environmental iodine deficiency in the UK--Derbyshire: a review.
AB  - Endemic goitre was prevalent in the population of Derbyshire in the UK for many
      centuries until it declined from the 1930s. A contemporary medical survey showed
      that endemicity of goitre was particularly higher in the Carboniferous limestone
      areas of the Derbyshire-Peak District. Unlike classical goitrous areas of the
      world, where the distribution of goitre has been found to be related to the
      iodine content in the environment, there is no such relationship reported for the
      Derbyshire-Peak District area. The present study reviews the presence of endemic
      goitre in this area with reference to iodine in different environmental media
      using past and present data. In comparison with the world average values, the
      iodine contents in the soil and sediment in the Peak District are not deficient,
      but compared to England, Wales and Scotland averages, these levels are low. As no
      information on the mobility and bioavailability of iodine of this area is
      available, a cautious approach is necessary before any assumption is made on the
      aetiology of endemic goitre. The study also discusses some hypotheses relating to
      the possible cause of endemic goitre in the limestone areas. Further research
      needs are suggested depending on the land use and geochemistry of the Peak
      District to determine the underlying causes of the former endemic goitre in this
      area.

PMID- 15719163
TI  - Removal of arsenic in tailings by soil flushing and the remediation process
      monitoring.
AB  - In order to investigate the optimum conditions for the application of soil
      flushing of arsenic, a batch test was carried out using EDTA at various
      concentration and pH levels. Based on the optimum condition derived from the
      batch test, a column test was conducted to examine the feasibility of the soil
      flushing technology under field-equivalent conditions. In this column test, a low
      flushing solution flow rate showed a significantly higher As removal efficiency
      (71.6%) than a high flow rate (56.3%). TCLP (toxicity characteristic leaching
      procedure) and a seed germination test were carried out to monitor the toxicity
      both during and after the treatment. The finally treated tailings were shown to
      be significantly remediated, having a reduced toxicity by both the TCLP and seed
      germination tests.

PMID- 15719164
TI  - Trends in sediment metal concentrations in the River Avoca, South-east Ireland.
AB  - Variation in sediment metal concentrations in the River Avoca, which is severely
      polluted by acid mine drainage (AMD) discharged from the abandoned sulphur and
      copper mines in Avoca, is reported. A survey of surface and subsurface sediments
      was repeated after seven years during exceptionally low flow conditions in 2001.
      The present study found that the reference (up-stream) site used in the original
      1994 study was itself impacted by AMD, showing sediment metal enrichment by AMD
      to be greater than originally thought. The new reference site contained elevated
      Pb (570 microg g(-1)) in the subsurface sediment due to abandoned Pb-Zn mines 25
      km further upstream. Concentrations of Cu (43 microg g(-1)), Zn (349 microg g(
      1)) and Fe (4.0%) were normal for uncontaminated rivers. All the downstream sites
      showed sediment metal enrichment arising from the AMD (Cu and Zn p < 0.001; Fe p
      < 0.01). Subsurface concentrations of metals immediately below the mixing zone
      were Cu 904 microg g-1 (sd 335), Zn 723 microg g-1 (sd 93), Fe 6.3% (sd 1.5) and
      Pb 463 microg g(-1) (sd 279). Monthly variation in metal concentrations at sites
      was not significantly different (p > 0.05). Although surface sediment metal
      concentrations were more variable, they followed similar trends to subsurface
      sediment. There were no significant differences in the subsurface sediment
      concentrations for either Cu or Zn over the period 1994 and 2001 immediately
      below the mines, although at the lowest site Zn had decreased by 35% over the
      period (p < 0.01). However there was a significant (p < 0.01) decrease over the
      period in the Fe concentration at all the impacted sites. This corresponds to a
      reduction in Fe concentration in the AMD and indicates that some remediation has
      occurred in the river since 1994.

PMID- 15719165
TI  - Principal biogeochemical factors affecting the speciation and transport of
      mercury through the terrestrial environment.
AB  - It is increasingly becoming known that mercury transport and speciation in the
      terrestrial environment play major roles in methyl-mercury bioaccumulation
      potential in surface water. This review discusses the principal biogeochemical
      reactions affecting the transport and speciation of mercury in the terrestrial
      watershed. The issues presented are mercury-ligand formation, mercury
      adsorption/desorption, and elemental mercury reduction and volatilization. In
      terrestrial environments, OH-, Cl- and S- ions have the largest influence on
      ligand formation. Under oxidized surface soil conditions Hg(OH)2, HgCl2, HgOH+,
      HgS, and Hg0 are the predominant inorganic mercury forms. In reduced
      environments, common mercury forms are HgSH+, HgOHSH, and HgClSH. Many of these
      mercury forms are further bound to organic and inorganic ligands. Mercury
      adsorption to mineral and organic surfaces is mainly dictated by two factors: pH
      and dissolved ions. An increase in Cl- concentration and a decrease in pH can,
      together or separately, decrease mercury adsorption. Clay and organic soils have
      the highest capability of adsorbing mercury. Important parameters that increase
      abiotic inorganic mercury reduction are availability of electron donors, low
      redox potential, and sunlight intensity. Primary factors that increase
      volatilization are soil permeability and temperature. A decrease in mercury
      adsorption and an increase in soil moisture will also increase volatilization.
      The effect of climate on biogeochemical reactions in the terrestrial watershed
      indicates mercury speciation and transport to receiving water will vary on a
      regional basis.

PMID- 15719167
TI  - Forkhead transcription factors in immunology.
AB  - The forkhead (Fox) gene family comprises a diverse group of "winged-helix"
      transcription factors that play important roles in development, metabolism,
      cancer and aging. Recently, several forkhead genes have been demonstrated to play
      critical roles in lymphocyte development and effector function, including Foxp3
      in the development of regulatory T cells, Foxj1 and Foxo3a in the regulation of
      CD4+ T cell tolerance, and Foxn1 in thymic development. Roles for other forkhead
      genes have also been proposed, including Foxp1 in macrophage differentiation,
      Foxq1 in natural killer cell effector function and Foxd2 in T cell activation.
      Thus, forkhead genes promise insight into the mechanisms of immunoregulation in
      several immune cell lineages, and their dysregulation likely contributes to the
      pathogenesis of several immunological disorders, suggesting that their study will
      lead to the development of novel therapeutic agents.

PMID- 15719168
TI  - Heparan sulfate-protein interactions: therapeutic potential through structure
      function insights.
AB  - Heparin and the related glycosaminoglycan, heparan sulfate, bind a myriad of
      proteins. The structural diversity of heparin and heparan sulfates is enormous,
      but differences in the conformational flexibility of the monosaccharide
      constituents add extra complexity and may influence protein binding. Silencing
      genes for heparin/ heparan sulfate biosynthetic enzymes profoundly affects
      mammalian development. Thus, altering the structure of heparan sulfate chains can
      alter protein binding and embryo development. Different heparan sulfate
      structures are located in particular tissue sites, and these structures are
      recognised by different sets of proteins. Regulation of certain heparan sulfate
      protein interactions by pH or cations is described. Heparin/heparan sulfate
      structures are viewed as potential therapeutics for a variety of diseases. An
      understanding at the molecular and functional levels of the specificity and
      affinity of heparan sulfate-protein interactions is crucial for designing heparin
      inspired drugs. How the development of synthesis techniques is facilitating
      structure-function analyses and drug development is discussed.

PMID- 15719169
TI  - Missense mutations resulting in type 1 lissencephaly.
AB  - Proper human brain formation is dependent upon the integrated activity of
      multiple genes. Malfunctioning of key proteins results in brain developmental
      abnormalities. Mutation(s) in the LIS1 gene or the X-linked gene doublecortin
      (DCX) results in a spectrum of disorders including lissencephaly, or "smooth
      brain", and subcortical band heterotopia, or "doublecortex". Here, we will focus
      on a particular subset of missense mutations in these two genes and their effect
      on protein structure and function.

PMID- 15719170
TI  - The evolution of domain arrangements in proteins and interaction networks.
AB  - Proteins are composed of domains, which are conserved evolutionary units that
      often also correspond to functional units and can frequently be detected with
      reasonable reliability using computational methods. Most proteins consist of two
      or more domains, giving rise to a variety of combinations of domains. Another
      level of complexity arises because proteins themselves can form complexes with
      small molecules, nucleic acids and other proteins. The networks of both domain
      combinations and protein interactions can be conceptualised as graphs, and these
      graphs can be analysed conveniently by computational methods. In this review we
      summarise facts and hypotheses about the evolution of domains in multi-domain
      proteins and protein complexes, and the tools and data resources available to
      study them.

PMID- 15719171
TI  - Binding site of activators of the cystic fibrosis transmembrane conductance
      regulator in the nucleotide binding domains.
AB  - The use of substances that could activate the defective chloride channels of the
      mutant cystic fibrosis transmembrane conductance regulator (CFTR) has been
      suggested as possible therapy for cystic fibrosis. Using epithelia formed by
      cells stably transfected with wildtype or mutant (G551D, G1349D) CFTR, we
      estimated the apparent dissociation constant, K(D), of a series of CFTR
      activators by measuring the increase in the apical membrane current. Modification
      of apparent K(D) of CFTR activators by mutations of the nucleotide-binding
      domains (NBDs) suggests that the binding site might be in these regions. The
      human NBD structure was predicted by homology with murine NBD1. An NBD1-NBD2
      complex was constructed by overlying monomers to a bacterial ABC transporter NBD
      dimer in the "head-to-tail" conformation. Binding sites for CFTR activators were
      predicted by molecular docking. Comparison of theoretical binding free energy
      estimated in the model to free energy estimated from the apparent dissociation
      constants, K(D), resulted in a remarkably good correlation coefficient for one of
      the putative binding sites, located in the interface between NBD1 and NBD2.

PMID- 15719172
TI  - Cofilin activity during insulin-like growth factor I-stimulated neuroblastoma
      cell motility.
AB  - Insulin-like growth factor I (IGF-I) is a potent stimulator of neuroblastoma cell
      motility. Cell motility requires lamellipodium extension at the leading edge of
      the cell through organized actin polymerization, and IGF-I stimulates
      lamellipodial elaboration in human neuroblastoma cells. Rac is a Rho GTPase that
      stimulates lamellipodial formation via the regulation of actin polymerization. In
      this study, we show that IGF-I-stimulated phosphatidylinositol 3-kinase (PI-3K)
      activity promotes rac activation and subsequent activation of the down- stream
      effectors LIM kinase and cofilin. Overexpression of wild-type LIM kinase and wild
      type Xenopus ADF/cofilin (XAC) suppresses IGF-I-stimulated motility in SH-SY5Y
      cells, while expression of dominant negative LIM kinase and constitutively active
      XAC increases SH-SY5Y motility in the absence of IGF-I stimulation. These results
      suggest that regulation by cofilin of actin depolymerization is important in the
      process of neuroblastoma cell motility, and IGF-I regulates cofilin activity in
      part through PI-3K, rac, and LIM kinase.

PMID- 15719173
TI  - Association, mutual stabilization, and transcriptional activity of the STRA13 and
      MSP58 proteins.
AB  - STRA13 is a hypoxia-inducible bHLH transcription factor implicated in the
      pVHL/HIF, TGF-beta, and Jak/STAT pathways. To further characterize the STRA13
      protein-interacting network and mechanisms of STRA13-dependent transcription, we
      utilized yeast two-hybrid screening. Here we report on STRA13 interaction with
      the cell cycle-associated transcription factor MSP58. We demonstrated that the
      basic domain of STRA13 and the FHA domain of MSP58 are essential for this
      association. We performed phospho-peptide mapping of both MSP58 and STRA13 and
      showed that their association was modulated by the STRA13 phosphorylation status.
      STRA13/MSP58 complex formation protected both proteins from the proteasome
      mediated degradation, extending their half-lives considerably. STRA13 and MSP58
      synergistically co-operated in the STRA13 promoter-driven transcription
      repression. Both proteins were co-localized in the nucleus and showed transcript
      accumulation during the S phase of the cell cycle. Thus, we characterize a novel
      STRA13-associated transcription repression complex and provide a link between
      cell cycle regulation and STRA13 activity.

PMID- 15719174
TI  - The novel human gene aprataxin is directly involved in DNA single-strand-break
      repair.
AB  - The cells of an ataxia-oculomotor apraxia type 1 (AOA1) patient, homozygous for a
      new aprataxin mutation (T739C), were treated with camptothecin, an inhibitor of
      DNA topoisomerase I which induces DNA single-strand breaks. DNA damage was
      evaluated by cytogenetic analysis of chromosomal aberrations. The results
      obtained showed marked and dose-related increases in induced chromosomal
      aberrations in the patient and her heterozygous mother compared to the
      intrafamilial wild-type control. The alkaline comet assay confirmed this pattern.
      Moreover, the AOA1 cells did not show hypersensitivity to ionizing radiation,
      i.e. X-rays. These findings clearly indicate the direct involvement of aprataxin
      in the DNA single-strand-break repair machinery.

PMID- 15719175
TI  - Protein profiling of 3T3-L1 adipocyte differentiation and (tumor necrosis factor
      alpha-mediated) starvation.
AB  - The increased incidence of obesity and related disorders in Western societies
      requires a thorough understanding of the adipogenic process. Data at the protein
      level of this process are scarce. Therefore we performed a proteome analysis of
      differentiating and starving 3T3-L1 cells using two-dimensional gel
      electrophoresis combined with mass spectrometry. Effects of different starvation
      conditions were examined by subjecting 3T3-L1 adipocytes to caloric restriction,
      either in the absence or the presence of the lipolysis inducer tumor necrosis
      factor-alpha. Ninety-three differentially expressed proteins were found during
      differentiation and starvation of 3T3-L1 cells, 50 of which were identified.
      GenMAPP/MAPP-finder software revealed a non-reciprocal regulation of the
      glycolytic pathway during 3T3-L1 differentiation followed by starvation.
      Furthermore, proteins involved in growth regulation, cytoskeletal rearrangements
      and protein modification, 16 of which have not been described before in 3T3-L1
      cells, were identified. In conclusion, our data provide valuable information for
      further understanding of the adipogenic process.

PMID- 15719176
TI  - Pseudoaneurysm of the internal mammary artery as an unusual cause of post
      sternotomy hemorrhage: the role of multislice computed tomography in the
      diagnosis and treatment planning.
AB  - Pseudoaneurysm of the internal mammary artery (IMA) following median sternotomy
      is extremely rare. To date, the reported cases are only in single figures. The
      majority of these pseudoaneurysms were suspected from the clinical presentation,
      echocardiography or computed tomography (CT) but were only confirmed on contrast
      angiography. This case report demonstrates the current ability to carry out
      detailed vascular imaging on a 16-slice CT scanner. This accurate delineation of
      the pseudoaneurysm allowed targeted therapeutic embolization to be performed
      without unnecessary angiographic imaging.

PMID- 15719178
TI  - Transcatheter closure of patent foramen ovale in patients with platypnea
      orthodeoxia: results of a multicentric French registry.
AB  - BACKGROUND: Dyspnea and the decrease in arterial saturation in the upright
      position in elderly subjects is described as platypnea-orthodeoxia syndrome
      (POS). POS is secondary to the occurrence of an atrial right-to-left shunt
      through a patent foramen ovale (PFO). METHODS: This French multicentric study
      reports on 78 patients (mean age 67 +/- 11.3 years) with POS who had
      transcatheter closure of the PFO; frequently associated diseases were
      pneumonectomy (n = 36) and an ascending aortic aneurysm (n = 11). In all
      patients, the diagnosis was confirmed by transthoracic or/and transesophageal
      echocardiography. Five different closure devices were used: Amplatz (n = 45),
      Cardioseal (n = 13), Sideris (n = 11), Das Angel Wings (n = 8) and Starflex (n =
      1). Closure was successful in 76 patients (97%). RESULTS: Oxygen saturation
      increased immediately after occlusion from 84.6 +/- 10.7% to 95.1 +/- 6.4% (p <
      0.001) and dyspnea improved from grade 2.7 +/- 0.7 to grade 1 +/- 1 (p < 0.001).
      A small residual shunt was immediately observed in 5 patients (3 with the
      Cardioseal device, 1 with the Sideris and 1 with the Amplatz) leading to the
      implantation of a second device in one case (Cardioseal). Two early deaths
      occurred unrelated to the procedure (one due to sepsis probably related to
      pneumonectomy, another due to respiratory insufficiency). Other complications
      were: a small shunt between the aorta and the left atrium, two atrial
      fibrillations and a left-sided thrombus which disappeared with anticoagulant
      therapy. At a mean follow-up of 15 +/- 12 months, there were 7 late deaths
      related to the underlying disease. CONCLUSION: Percutaneous occlusion of the
      foramen ovale is safe and gives excellent results thanks to continuing
      improvement in available devices. This technique enables some patients in an
      unstable condition to avoid a surgical closure.

PMID- 15719177
TI  - Endovascular placement of an extraluminal femoropopliteal bypass graft in human
      cadavers.
AB  - PURPOSE: A method to create an extraluminal femoropopliteal bypass graft using
      endovascular techniques was evaluated in situ on cadaver extremities in an
      attempt to develop a minimally invasive alternative technique for the management
      of infrainguinal occlusive arterial disease. METHODS: The endovascular placement
      of an extraluminal femoropopliteal bypass graft was undertaken in 5 cadaver legs.
      Following percutaneous access to the popliteal artery (PA) or common femoral
      artery (CFA), a Rosch-Uchida needle was used to perforate the vascular wall,
      followed by the creation of an extraluminal tract using a looped wire and
      catheter. Once the desired level was reached the needle was again used to
      perforate the vascular wall of the proximal superficial femoral artery (SFA) or
      PA depending on the access used. Self-expanding expanded polytetrafluoroethylene
      (ePTFE) stent-grafts were then deployed to establish the extraluminal
      femoropopliteal bypass connecting the two arterial puncture sites. Following
      dilatation of the stent-graft, angiography was performed to assess the
      endoprostheses and to look for contrast leaks. RESULTS: Technical success was
      achieved in all 5 legs. Procedure time varied from 15 to 30 min. The angiographic
      studies performed immediately after completion of the bypass procedure showed
      patency of the grafts with no evidence of kinking or leakage in any of the cases.
      CONCLUSION: This study has proved that the endovascular placement of an
      extraluminal femoropopliteal bypass graft in human cadaver legs using
      endovascular techniques under fluoroscopic control is technically feasible.

PMID- 15719179
TI  - Potentially life-threatening neck abscesses: therapeutic management under CT
      guided drainage.
AB  - PURPOSE: To evaluate the effectiveness of CT-guided drainage of potentially life
      threatening neck abscesses. METHODS: Between September 2001 and December 2003, 15
      patients presented to the emergency room with potentially life-threatening neck
      abscesses. Their clinical condition was critical due to the abscess size (larger
      than 3 cm in diameter; mean diameter 5.2 cm, SD 0.91 cm) and/or abscess location.
      A CT scan was carried out immediately to assess the lesion. At the same time,
      under CT guidance, an 8 Fr trocar-type pigtail catheter was inserted, in order to
      drain the abscess. The decision to drain percutaneously was based on a consensus
      between the surgical, infectious disease and radiology teams . The catheter was
      kept in place until drainage stopped, and a follow-up scan was performed.
      RESULTS: In 14 (93%) patients, the abscess was completely drained, and in 1 (7%)
      case the collection was still present because of multiple internal septation.
      That patient was treated by surgical management. The catheter was in place for a
      mean of 3 days (SD 0.96 day). CONCLUSION: Despite the fact that the number of our
      patients is small, CT-guided percutaneous drainage seems to be a fast, safe and
      highly effective low-cost method for the treatment of potentially life
      threatening neck abscesses.

PMID- 15719180
TI  - Stent-based nitric oxide delivery reducing neointimal proliferation in a porcine
      carotid overstretch injury model.
AB  - BACKGROUND: The effects of nitric acid (NO) on vessel response to injury include
      the inhibition of platelet adhesion, platelet aggregation, leukocyte adhesion and
      smooth muscle cell proliferation. Releasing NO from a stent might reduce the
      clinical problem of restenosis. The present study was designed to examine whether
      an NO-eluting covered stent can prevent neointimal formation in a porcine carotid
      overstretch injury model. METHODS: The interior of a self-expanding
      polytetrafluoroethylene (ePTFE)-covered aSpire stent was coated with silicone,
      which contained 23.6 microg or 54.5 microg sodium nitroprusside (SNP, NO
      releasing compound). The stent was implanted into carotid artery. Six pigs were
      implanted with stents, one high-dose SNP and one uncoated control, following
      balloon overstretch injury of the carotid artery with a balloon-to-artery ratio
      of 1.3:1. RESULTS: No local or systemic toxicity was evidenced in the six pigs
      after carotid artery implantation with either low- or high-dose stents within a
      week. At day 28, the mean intimal thickness was 0.12 +/- 0.05 mm for NO-eluting
      stents and 0.43 +/- 0.09 mm for uncoated stents (p = 0.008). The mean neointimal
      area was reduced from 2.40 +/- 0.39 mm2 for control stents to 0.49 +/- 0.16 mm2
      for NO-eluting stents (p < 0.0001), which resulted in a 24% reduction of
      angiographic vessel narrowing. CONCLUSIONS: The NO-eluting ePTFE-covered stent is
      feasible and effectively reduces in-stent neointimal hyperplasia at 28 days in a
      porcine carotid overstretch model.

PMID- 15719181
TI  - Treatment of ureteroarterial fistulae with covered vascular endoprostheses and
      ureteral occlusion.
AB  - BACKGROUND: Ureteroarterial fistulae (UAFs) are a rare entity, often difficult to
      identify, and associated with a high mortality rate. This fact has been
      attributed to a delay in diagnosis and treatment. Five conditions that can
      predispose to the development of this uncommon entity have been described: prior
      pelvic surgery, prolonged ureteral stenting, radiation therapy, previous vascular
      surgery and vascular pathology. METHODS: We present 4 patients with UAFs and at
      least three of the above-mentioned conditions. Ureteral ischemia and subsequent
      necrosis promote the formation of these fistulae. The constant pulsation of the
      iliac artery is transmitted to an already compromised ureter containing a stiff
      intraluminal foreign body, resulting in pressure necrosis, most likely where the
      ureter crosses the iliac artery. RESULTS AND CONCLUSION: Cases were managed
      percutaneously with a combination of the deployment of a covered prosthesis and,
      when needed, with mechanical occlusion of the ureter. Hematuria stopped in all
      the patients with no evidence of immediate rebleeding. One patient presented a
      new episode of vaginal bleeding 13 months after endograft placement and ureteral
      embolization. Arteriography showed the presence of a hypogastric artery
      pseudoaneurysm that was occluded using coils. No new bleeding has occurred in
      this patient 12 months after the second embolization. At present all 4 patients
      are alive with follow-up periods of 5, 9, 11 and 25 months since the first
      procedure.

PMID- 15719182
TI  - Pseudoaneurysm after spontaneous rupture of renal angiomyolipoma in tuberous
      sclerosis: successful treatment with percutaneous thrombin injection.
AB  - We report a case of a large perinephric pseudoaneurysm due to spontaneous rupture
      of renal angiomyolipoma, occluded by percutaneous thrombin injection under
      ultrasound guidance in a young woman affected by tuberous sclerosis.

PMID- 15719183
TI  - Ectopic varices in the gastrointestinal tract: short- and long-term outcomes of
      percutaneous therapy.
AB  - To evaluate the results of percutaneous management of ectopic varices, a
      retrospective review was carried out of 14 patients (9 men, 5 women; mean age 58
      years) who between 1992 and 2001 underwent interventional radiological techniques
      for management of bleeding ectopic varices. A history of prior abdominal surgery
      was present in 12 of 14 patients. The interval between the surgery and
      percutaneous intervention ranged from 2 to 38 years. Transhepatic portal
      venography confirmed ectopic varices to be the source of portal hypertension
      related gastrointestinal bleeding. Embolization of the ectopic varices was
      performed by a transhepatic approach with coil embolization of the veins draining
      into the ectopic varices. Transjugular intrahepatic portosystemic shunt (TIPS)
      was performed in the standard fashion. Eighteen procedures (12 primary coil
      embolizations, 1 primary TIPS, 2 re-embolizations, 3 secondary TIPS) were
      performed in 13 patients. One patient was not a candidate for percutaneous
      treatment. All interventions but one (re-embolization) were technically
      successful. In 2 of 18 interventions, re-bleeding occurred within 72 hr (both
      embolization patients). Recurrent bleeding (23 days to 27 months after initial
      intervention) was identified in 9 procedures (8 coil embolizations, 1 TIPS due to
      biliary fistula). One patient had TIPS revision because of ultrasound
      surveillance findings. New encephalopathy developed in 2 of 4 TIPS patients.
      Percutaneous coil embolization is a simple and safe treatment for bleeding
      ectopic varices; however, recurrent bleeding is frequent and reintervention often
      required. TIPS can offer good control of bleeding at the expense of a more
      complex procedure and associated risk of encephalopathy.

PMID- 15719184
TI  - Uterine artery embolization for fibroid disease is not experimental.

PMID- 15719185
TI  - Transcatheter coil embolization of an aneurysm of the pancreatico-duodenal artery
      with occluded celiac trunk.
AB  - We report on a case of a wide-necked aneurysm of the pancreatico-duodenal artery
      with occlusion of the celiac trunk in an asymptomatic patient. The aneurysm was
      considered to be at high risk of rupture. Successful embolization after
      interdisciplinary consultation was followed with color-coded duplex ultrasound
      (CCDS) demonstrating significant flow reduction. Three weeks later CCDS and
      angiography demonstrated exclusion of the aneurysm and a patent arterial supply
      of the liver and spleen fed by superior mesenteric artery (SMA) collaterals. The
      patient has done well so far, without major adverse clinical events or evidence
      for tissue necrosis of the liver, pancreas or spleen. Discussion of the case and
      review of the literature indicate that transcatheter embolization is the therapy
      of choice even in complicated cases.

PMID- 15719186
TI  - A flexible stent with small intestinal submucosa covering for direct intrahepatic
      portocaval shunt: experimental pilot study in swine.
AB  - The suitability of the flexible sandwich Zilver stent-graft (SZSG) with a
      biologically active tissue layer (small intestinal submucosa) for creation of the
      intravascular ultrasound (IVUS)-guided direct intrahepatic portocaval shunt
      (DIPS) was explored in six young swine in a search for a flexible system to
      replace the rigid polytetrafluoroethylene (PTFE) stent originally used by this
      group with limited success. The portal vein was punctured from the inferior vena
      cava through the caudate lobe of the liver using IVUS guidance. After balloon
      dilation of the puncture tract, DIPS was successfully created in all animals with
      use of an SZSG 9 mm in diameter and 6 cm or 8 cm long. Only one DIPS remained
      well patent at 14 days when the animal had to be killed because of
      encephalopathy. DIPS in the other five animals were found to be either severely
      stenosed (3 animals) or occluded (2 animals) at 4 weeks due to accelerated
      formation of neointimal hyperplasia (NIH) in the liver parenchymal portion of the
      shunt and superimposed thrombosis. The lack of high pressure in the portal system
      contributed to early endograft closure. The flexible stent and the covering fail
      badly. The reason for this could be due to either component. More work is
      required to find a reliable flexible system with long-term patency. Exploration
      of the IVUS-guided direct extrahepatic portocaval shunt is suggested.

PMID- 15719187
TI  - Four- and eight-channel aortoiliac CT angiography: a comparative study.
AB  - PURPOSE: To compare performance parameters, contrast material load and radiation
      dose in a patient cohort having aortoiliac CT angiography using 4- and 8-channel
      multidetector CT (MDCT) systems. METHODS: Eighteen patients with abdominal aortic
      aneurysms underwent initial 4-channel and follow-up 8-channel MDCT angiography.
      Both the 4- and 8-channel MDCT systems utilized a matrix detector of 16 x 1.25 mm
      rows. Scan coverage included the abdominal aorta and iliac arteries to the level
      of the proximal femoral arteries. For 4-channel MDCT, nominal slice thickness and
      beam pitch were 1.25 mm and 1.5, respectively, and for 8-channel MDCT they were
      1.25 mm and 1.35 or 1.65 respectively. Scan duration, iodinated contrast material
      load and mean aortoiliac attenuation were compared retrospectively. Comparative
      radiation dose measurements for 4- and 8-channel MDCT were obtained using a
      multiple scan average dose technique on an abdominal phantom. RESULTS: Compared
      with 4-channel MDCT, 8-channel MDCT aortoiliac angiography was performed with
      equivalent collimation, decreased contrast load (mean 45% decrease: 144 ml versus
      83 ml of 300 mg iodine/ml contrast material) and decreased acquisition time (mean
      51% shorter: 34.4 sec versus 16.9 sec) without a significant change in mean
      aortic enhancement (299 HU versus 300 HU, p > 0.05). Radiation dose was 2 rad for
      the 4-channel system and 2/1.5 rad for the 8-channel system at 1.35/1.65 pitch
      respectively. CONCLUSION: Compared with 4-channel MDCT, aortoiliac CT angiography
      with 8-channel MDCT produces equivalent z-axis resolution with decreased contrast
      load and acquisition time without increased radiation exposure.

PMID- 15719188
TI  - Long-term indwelling seton for complex anal fistulas in Crohn's disease.
AB  - PURPOSE: This study was designed to review the results of long-term indwelling
      seton or depezzar catheter in the management of perianal Crohn's disease.
      METHODS: A retrospective case review from data extracted from a prospective
      endorectal ultrasound database was performed. All patients underwent an
      intraoperative endorectal ultrasound to identify the extent of the fistulas and
      to assess anal wall thickness. Fistulas were classified by Parks' criteria. All
      patients then underwent insertion of a seton or depezzar catheter under
      ultrasound guidance. All patients were followed clinically and with endorectal
      ultrasound by the senior author. Outcome measures included symptom control,
      number of procedures required, fecal continence, and reduction in anal wall
      thickness. RESULTS: Twenty-eight patients with 43 complex perianal Crohn's
      fistulas were identified. Median follow-up was 13 (range, 2-81) months. Twenty
      one percent of patients developed recurrent or new perianal symptoms while the
      seton was in situ. Eleven percent of patients required further surgical
      intervention. The median anal wall thickness at the time of diagnosis was 18.5 mm
      reducing to a median of 14 mm after seton insertion and symptom control (P <
      0.02). No patient reported a deterioration in fecal continence after seton
      insertion. In multivariate analysis, patient age (P < 0.005), reduction in anal
      wall thickness after seton insertion (P < 0.04), and length of follow-up (P <
      0.03) were significant predictors of long-term symptom control. CONCLUSIONS: Long
      term indwelling seton is an effective management modality for complex perianal
      Crohn's fistulas, which does not negatively impact fecal continence. Clinical
      symptoms and course are associated with anal wall thickness as measured by
      endorectal ultrasound.

PMID- 15719189
TI  - Colonic J-pouch-anal anastomosis for rectal cancer: a prospective, randomized
      study comparing handsewn vs. stapled anastomosis.
AB  - PURPOSE: Colonic J-pouch-anal anastomosis performed after complete proctectomy
      and total mesorectal excision for adenocarcinoma of the rectum can be handsewn or
      stapled. Stapling the coloanal anastomosis is believed to shorten operating time
      and reduce morbidity, but there are no randomized trials comparing the
      techniques. METHODS: Between January 1999 and May 2001, all patients with rectal
      adenocarcinoma requiring total mesorectal excision were randomized
      intraoperatively to handsewn or stapled anastomosis. Mortality, intraoperative,
      and postoperative findings and functional results at 3, 6, and 12 months were
      analyzed. RESULTS: Thirty-seven patients (12 females; mean age, 60 +/- 10 years)
      were randomized (stapled group: n = 20; handsewn group: n = 17). The two groups
      were comparable for age, gender, distance between the tumor and the levator ani,
      tumor volume, and use of preoperative radiotherapy (3 in each group). Morbidity
      did not differ between stapled group (3/20) and handsewn group (4/17; P > 0.05).
      Mean +/- standard deviation operative time was shorter in stapled group (261 +/-
      40 minutes) than in handsewn group (314 +/- 46 minutes; P = 0.0008), and median
      distance between the anastomosis and the anal verge was shorter in handsewn group
      (19 +/- 9 mm) than in stapled group (27 +/- 8 mm; P = 0.01). Three patients of
      handsewn group and none of stapled group developed an anastomotic stricture
      requiring a single digital dilation (not significant). Number of stools per 24
      hours, urgency, incidence of fragmented stools, degree of continence, requirement
      for protective pad, and/or need to take medication at 3, 6, and 12 months were
      similar in both groups. CONCLUSIONS: Stapled co-loanal anastomosis is
      significantly faster than handsewn CAA and has similar functional results. It
      should be the preferred technique when it is feasible.

PMID- 15719190
TI  - Primary perineal wound closure after preoperative radiotherapy and
      abdominoperineal resection has a high incidence of wound failure.
AB  - PURPOSE: Neoadjuvant radiation therapy has been used increasingly to downstage
      rectal cancer and decrease local recurrence. Despite its efficacy, preoperative
      radiation therapy may inhibit healing and contribute to wound complications. This
      study was designed to evaluate perineal wound complications after
      abdominoperineal resection. METHODS: The clinical records of a consecutive series
      of patients who underwent abdominoperineal resection for rectal carcinoma between
      1988 and 2002 were reviewed. Demographic data, disease stage, and use of
      preoperative radiation therapy were recorded. Major wound complications included
      delayed wound healing (>1 month), wound infection requiring drainage/debridement,
      or reoperation. RESULTS: A total of 160 patients underwent abdominoperineal
      resection with primary closure of the perineal wound (mean age, 63 +/- 12 years);
      117 (73 percent) patients received preoperative radiation therapy; 114 received
      radiation therapy for rectal cancer (radiation therapy + chemotherapy = 107,
      radiation therapy alone = 7); 3 received radiation therapy for other pelvic
      malignancies. Median radiation dose was 5,040 (range, 900-5,400) cGY. Overall
      wound complication rate was 41 percent. Major wound complication rate was 35
      percent. Delayed healing was the most common complication (24 percent), followed
      by infection (10 percent). Radiation therapy increased the risk of any wound
      complication (47 vs. 23 percent; P = 0.005), risk of a major wound complication
      (41 vs. 19 percent; P = 0.021), and risk of infection (14 vs. 0 percent; P =
      0.015). Risk of wound complications did not correlate with age, gender, disease
      stage, smoking, or diabetes. CONCLUSIONS: Wound complications are frequent after
      abdominoperineal resection and primary closure of the perineum. Preoperative
      radiation therapy doubles the rate of total and major perineal wound
      complications. Alternatives to primary perineal closure should be considered,
      particularly after radiation therapy.

PMID- 15719191
TI  - Postoperative change of mucosal inflammation at strictureplasty segment in
      Crohn's disease: cytokine production and endoscopic and histologic findings.
AB  - PURPOSE: This study was designed to examine postoperative change of mucosal
      inflammation at strictureplasty segment in Crohn's disease mainly by cytokine
      measurements. METHODS: Patients who underwent strictureplasty for Crohn's disease
      in the terminal ileum were investigated. Mucosal samples at the strictureplasty
      site were obtained during operation. At 3, 6, and 12 months after operation,
      biopsy specimens were taken from the strictureplasty site and macroscopically
      normal ileum at endoscopy. Mucosal cytokine concentrations were measured by
      enzyme-linked immunosorbent assay. RESULTS: The mucosal concentrations of
      proinflammatory cytokines (interleukin-1beta, interleukin-6, interleukin-8, and
      tumor necrosis factor-alpha) and anti-inflammatory mediator (interleukin-1
      receptor antagonist) at the strictureplasty segment greatly increased at the time
      of operation. Interleukin-1beta, interleukin-1 receptor antagonist, interleukin
      6, interleukin-8, and tumor necrosis factor-alpha concentrations at the
      strictureplasty segment decreased during a 12-month period after operation.
      Twelve months after operation there was no significant difference in each
      cytokine concentration between the strictureplasty and macroscopically normal
      segments. The mucosal interleukin-1 receptor antagonist/interleukin-1beta ratio
      at the strictureplasty segment increased during a 12-month period after
      operation. Twelve months after operation there was no significant difference in
      the ratio between the strictureplasty and macroscopically normal segments. The
      endoscopic and histologic severities of mucosal inflammation at the
      strictureplasty site also decreased; however, their findings were not normalized
      during the study. CONCLUSIONS: During one year after strictureplasty for Crohn's
      disease, cytokine production at the strictureplasty segment was decreased to the
      level of the macroscopically normal ileum and an imbalance between
      proinflammatory and antiinflammatory cytokines was corrected.

PMID- 15719192
TI  - Investigation of APC mutations in a Turkish familial adenomatous polyposis family
      by heterodublex analysis.
AB  - PURPOSE: Familial adenomatous polyposis is an autosomal dominant disease
      characterized by the presence of 100 or more colorectal adenomatous polyps.
      Mutations in the adenomatous polyposis coli gene are primarily responsible for
      the development of this disease. This study was designed to investigation of
      adenomatous polyposis coli (APC) gene mutations in members of familial
      adenomatous polyposis family to identify individuals at risk of the disease.
      METHODS: We examined one patient with familial adenomatous polyposis and 21
      family members including one affected person from familial adenomatous polyposis
      and 20 nonsymptomatic persons. We studied E, D, F, and G segments of exon 15 of
      the adenomatous polyposis coli gene by heteroduplex analysis. RESULTS: We used
      silver staining method for staining. We found a mutation for five persons at
      segment F of exon 15 of the adenomatous polyposis coli gene. Two of them were
      affected by colorectal cancer, one of whom was the proband, and the other three
      were nonsymptomatic family members. The pathogenetic mutation was a T deletion at
      codon 1172, causing a frameshift in the adenomatous polyposis coli gene, as a
      result of the sequencing analysis of these cases. CONCLUSIONS: Investigation of
      adenomatous polyposis coli gene mutations is very important for the
      identification of genetic susceptibility to colorectal cancer and for the
      definition of tumor developing at an early stage. Furthermore, the identification
      of this mutation for the first time in a Turkish family will be useful to foster
      further studies on familial adenomatous polyposis in Turkey.

PMID- 15719193
TI  - Side-to-side stapled anastomosis strongly reduces anastomotic leak rates in
      Crohn's disease surgery.
AB  - PURPOSE: Anastomotic configuration may influence anastomotic leak rates. The aim
      of this study was to determine whether a side-to-side stapled ileocolonic
      anastomosis produces lower anastomotic leak rates than those with a handsewn end
      to-end ileocolonic anastomosis after ileocecal or ileocolonic resection for
      Crohn's disease. METHODS: A series of 122 consecutive patients underwent elective
      ileocecal or ileocolonic resection with ileocolonic anastomosis for Crohn's
      disease from January 1998 to June 2003: 71 had handsewn end-to-end anastomosis
      and 51 had side-to-side stapled anastomosis. The choice between the two
      anastomoses was left to the surgeon's preference. A retrospective analysis was
      performed to assess if there was any difference in anastomotic leak rates.
      RESULTS: The two groups were comparable in terms of age, gender, preoperative
      presence of abscess or fistula, history of smoking, and albumin levels. More
      patients were taking steroids in the handsewn group than in the stapled group. In
      the handsewn group there were 10 anastomotic leaks (14.1 percent) and in the
      stapled group there was 1 anastomotic leak (2.0 percent) (risk difference, +12.1
      percent; 95 percent confidence interval, 1.7-22.2; P = 0.02). Anastomotic
      configuration was the sole variable that influenced anastomotic leak rates at
      univariate analysis. Mortality was 1.4 percent in the handsewn group and 0
      percent in the stapled group. Complications other than anastomotic leak developed
      in 11 patients in the hand-sewn group and in 6 patients in the stapled group.
      Mean postoperative hospital stay was 12.3 days in the handsewn group and 9.7 days
      in the stapled group (P = 0.03). Excluding those patients who had an anastomotic
      leak, the difference was still present (handsewn group, 10.1 days; stapled group,
      9.1 days; P = 0.04). CONCLUSION: Although confirmation from randomized,
      controlled trials is required, side-to-side stapled anastomosis seems to
      substantially decrease anastomotic leak rates in surgical patients with Crohn's
      disease, compared with handsewn end-to-end anastomosis. Postoperative hospital
      stay decreased in the stapled anastomosis group, and this was not entirely a
      result of decreased anastomotic leak rates.

PMID- 15719194
TI  - Levels of persistent organochlorine contaminants in fish from Korea and their
      potential health risk.
AB  - Organochlorine contaminants in the muscles of sport and market fish were
      determined to understand the potential risks to humans consuming fish originating
      in Korea's coastal waters. Polychlorinated biphenyls (PCBs; sum of 22 congeners)
      and DDTs were the dominant contaminants, and their concentrations were in the
      range of 2.96 to 96.6 and 0.84 to 27.0 ng/g (wet weight basis), respectively. The
      highest PCB concentrations were found in samples taken from an industrial
      complex. Hexachlorocyclohexanes, chlordane-related compounds, and
      hexachlorobenzene concentrations were relatively low and ranged from 0.64 to 5.6,
      0.17 to 4.24, and 0.08 to 1.58, respectively. Sport fish had levels of PCBs and
      DDTs approximately two times higher than market fish, implying that sport fish
      posed high potential risk of contamination with OCs. Risk-based screening value
      (SV) based on U. S. Environmental Protection Agency (USEPA) method was calculated
      using the USEPA approach to identify the primary chemicals of concern. Total PCB
      concentrations in all sport and market fish exceeded the SV (5.04 ng/g based on
      total PCBs), but the other compounds were mostly below SV values. Based on the
      estimated SVs, PCB compounds were identified as potential chemicals of concern.

PMID- 15719195
TI  - Growth, nutritional composition, and hematology of Arctic charr (Salvelinus
      alpinus) exposed to toxaphene and tapeworm (Diphyllobothrium dendriticum) larvae.
AB  - Toxaphene, an organochlorine pesticide, is the major contaminant of Arctic charr
      (Salvelinus alpinus) in the Canadian Arctic. The objective of this study was to
      investigate the combined effects of toxaphene exposure and infection by the
      larval stage of the cestode Diphyllobothrium dendriticum on fish growth,
      nutritional composition, and hematology. Hatchery-reared Arctic charr were
      subjected to one of four treatments: (1) oral administration of corn oil
      (control); (2) single oral dose of 10 microg/g wet wt toxaphene dissolved in corn
      oil; (3) exposure to 15 larval D. dendriticum; and (4) exposure to toxaphene and
      D. dendriticum in combination. The experiment was run for 104 days. Mean final
      toxaphene concentrations in charr muscle were 0.121, 0.336, 0.131 and 0.458
      microg/g wet wt in each treatment group, respectively. Exposure to toxaphene and
      D. dendriticum decreased fish growth and condition as well muscle lipid and
      protein content. However, toxaphene did not increase the susceptibility of Arctic
      charr to parasite infection. Overall, 25 of 40 fish (62.5%) exposed to larval D.
      dendriticum became infected. Parasitized charr had decreased hematocrits and
      increased lymphocyte:erythrocyte ratios. Although total blood cell counts were
      decreased in all treatments compared with controls, differential leucocyte counts
      were unaffected. Our results suggest that toxaphene does not moderate Arctic
      charr resistance to D. dendriticum and there is no contaminant-parasite
      interaction at environmental levels.

PMID- 15719196
TI  - Effects of nontoxic shot regulations on lead accumulation in ducks and American
      woodcock in Canada.
AB  - Prior to the first nontoxic shot zones being established in Canada, a nationwide
      survey of lead (Pb) concentrations in wing bones of hatch year (HY) dabbling and
      diving ducks determined the incidence of elevated Pb exposure in waterfowl in
      different parts of the country (Scheuhammer and Dickson 1996). The main
      objectives of the present study were (1) to compare these previously collected
      data with the incidence of elevated Pb accumulation in the same species several
      years after the establishment of a national regulation in 1997 prohibiting the
      use of Pb shot for waterfowl hunting; and (2) to survey waterfowl hunters to
      determine reported levels of compliance with the nontoxic shot regulation.
      Average bone-Pb concentrations in dabbling ducks (mallards [Anas platyrhyncos]
      and American black ducks [Anas rubripes] combined) decreased significantly
      between 1989+1990 and 2000 (11 microg/g vs. 4.8 microg/g, respectively [p <
      0.01]). Ring-necked ducks (Aythya collaris) showed a similar decrease in mean
      bone-Pb concentrations, from 28 microg/g to 10 microg/g (p < 0.01). These
      declines in bone-Pb concentration were consistent with the results of a large
      anonymous hunter survey, which indicated a high level of reported compliance
      (>80%) with the nontoxic shot regulation among waterfowl hunters residing in
      Ontario and British Columbia. Conversely, American woodcock (Scolopax minor), an
      important upland game species not affected by the nontoxic shot regulation,
      showed no decrease in mean bone-Pb concentration since the national regulation
      came into effect (19 microg/g in 1995 vs. 21 microg/g in 2000). A majority (70%)
      of waterfowl hunters in British Columbia and Ontario who also hunt upland game
      birds report continued (legal) use of Pb shot for upland game bird hunting.

PMID- 15719197
TI  - Residues of toxaphene in insectivorous birds (Petrochelidon spp.) from the Rio
      Grande, Texas.
AB  - Although it has been documented that wildlife in the Rio Grande Valley (RGV)
      contain increased concentrations of organochlorine (OC) contaminants,
      particularly DDE, little has been published on residues of toxaphene throughout
      this major North American watershed. In this study, 28 liver composites from
      adult swallows (Petrochelidon spp.) collected along the Rio Grande from 1999
      through 2000 were analyzed for toxaphene residues using congener-specific gas
      chromatography-electron-capture negative ionization-mass spectrometry. Estimated
      total toxaphene concentrations ranged from 12 to 260 ng/g wet wt and were highest
      in samples from the lower RGV near Llano Grande Lake in Hidalgo and Cameron
      counties (Texas). Toxaphene congener profiles were relatively invariant
      throughout the watershed and were dominated by 2,2,5-endo,6-exo,8,8,9,10
      octachlorobornane (P-42a or B8-806) with lesser amounts of several other Cl(7)
      Cl(9) compounds, many of which remain unidentified. Petrochelidon spp. liver
      profiles appear to be intermediate in complexity between those in invertebrates
      and fish (more complex) and mammals (less complex) and differs somewhat from
      those reported for other avian species. In addition to other legacy OC
      contaminants, toxaphene residues were most concentrated in the lower RGV and
      accumulated at up to hundreds of parts per billion in these insect-eating birds,
      underscoring their utility as avian bioindicators of persistent organic
      pollutants.

PMID- 15719198
TI  - Isolation, cryopreservation, and mitogenesis of peripheral blood lymphocytes from
      chickens (Gallus domesticus) and wild herring gulls (Larus argentatus).
AB  - Monitoring the toxicity of environmental contaminants on the physiologic function
      of wild birds often includes measures of immune function. The purpose of this
      study was to apply methods of isolation, cryopreservation, and cell culture of
      chicken lymphocytes to blood samples from herring gulls, which are a sentinel
      species for biomonitoring studies in the Great Lakes and northern North America.
      Slow-spin centrifugation and density gradient isolation of lymphocytes were
      compared using chicken blood. Significant thrombocyte contamination of density
      gradient isolated samples (40% to 77% thrombocytes) led to the use of slow-spin
      centrifugation (2% thrombocytes) for blood from herring gulls. Cryopreserved
      blood samples were collected from adult and prefledgling herring gulls at sites
      of low environmental contamination around the Great Lakes and the Bay of Fundy
      between 1999 and 2002. Cryopreservation decreased the viability of lymphocytes
      from wild birds, but a high proportion of samples yielded enough live lymphocytes
      to assess function in culture. Cryopreserved lymphocytes from herring gulls
      proliferated in response to phytohemagglutinin (PHA), concanavalin-A, phorbol
      myristate acetate (PMA), PHA plus PMA, and lipopolysaccharide stimulation. Weber
      and Roswell Park Memorial Institute medium (RPMI) 1640 media were compared for
      culture of lymphocytes. Weber medium better supported chicken B-lymphocyte
      proliferation than RPMI 1640 and supported chicken T-lymphocyte proliferation of
      a similar magnitude as RPMI. Proliferation responses for lymphocytes from
      prefledgling herring gulls were stronger in Weber medium than RPMI medium,
      especially for PHA, for which there was no stimulation in RPMI. Proliferation
      responses of lymphocytes from adult herring gulls were up to twofold greater than
      that for prefledgling herring gulls. The magnitudes of proliferation responses
      were similar to that for chicken lymphocytes. These methods have subsequently
      proven useful in ecotoxicology studies that involve species in remote locations.

PMID- 15719199
TI  - Effects of calcium on the uptake and elimination of cadmium and zinc in Asiatic
      clams.
AB  - We examined the effects of Ca, one of the major ions contributing to water
      hardness, on the uptake and elimination of Cd and Zn in the Asiatic clam
      Corbicula fluminea, a common bivalve species in the rivers and streams of
      Southern China. Over the wide range of dissolved Cd (4.5 to 446 nM) and Zn (15.3
      to 1529 nM) concentrations, uptake of both metals increased with increasing
      dissolved metal concentration, showing Michaelis-Menten-type saturation kinetics.
      At each tested metal concentration, increased Ca concentration led to a
      significantly lower metal uptake. When the Ca, Cd, Zn concentrations were
      expressed as free-ion activities, Cd and Zn uptake data fitted the Michaelis
      Menten inhibition model well. We also quantified the effects of the two Ca
      blockers on metal uptake by the clams. Verapamil significantly inhibited the
      uptake Cd and Zn, but the inhibitive effect of lanthanum on metal uptake was more
      evident for Cd than for Zn. Ca did not significantly affect the assimilation
      efficiency of either metal from ingested phytoplankton, nor did it affect the
      elimination of the two metals during a 1-month depuration period. Our study has
      shown that Ca inhibited the uptake of metals from water; such an effect could be
      predicted based on the free-metal ion activities. Ca did not seem to have a
      direct effect on metal assimilation from food or metal elimination from the
      bivalve.

PMID- 15719200
TI  - Reproductive endocrine disruption in a sentinel species (Chrysemys picta) on Cape
      Cod, Massachusetts.
AB  - Freshwater turtles (Chrysemys picta) were collected from two sites on Cape Cod,
      MA. One site (Moody Pond), adjacent to the Massachusetts Military Reservation
      (MMR), was considered potentially impacted by toxic agents deriving from
      contaminant point sources on the MMR. The second (reference) site (Washburn
      Pond), to the east of the MMR, was considered not impacted by these pollutants
      and was chosen as a control site. Plasma estradiol 17 beta and vitellogenin were
      significantly lower in female turtles from Moody Pond. Ovarian follicular
      analysis indicated a significant decrease in the >16.00-mm follicular cohort in
      Moody Pond female turtles compared with Washburn Pond animals. Although
      testicular weight was lower at the Moody Pond site, histology, plasma
      testosterone, and sperm number were similar to these parameters in Washburn Pond
      animals. The data suggest that in Moody Pond, the reproductive capacity of
      turtles may be negatively affected by contaminants from the MMR.

PMID- 15719202
TI  - Identification of lymphatic endothelium in pediatric vascular tumors and
      malformations.
AB  - The distinction between lymphatic and other vascular vessels on microscopic
      sections is a challenging task. D2-40, a novel antibody, has been reported to be
      selective for lymphatic endothelium. We studied the specificity and sensitivity
      of D2-40 in pediatric vascular tumors and malformations. Fourteen lymphatic and
      11 vascular lesions were randomly selected and stained with D2-40 and CD31
      antibodies. The lymphatic lesions included 6 lymphatic malformations, 5 cystic
      hygromas (macrocystic lymphatic malformation), 2 lymphovenous malformations, and
      1 lymphangioma, and the vascular lesions comprised 3 infantile hemangiomas, 3
      Kaposiform hemangioendotheliomas, 2 tufted angiomas, 1 pyogenic granuloma, 1
      arteriovenous, and 1 venulocapillary malformations. The staining patterns of the
      vascular channels were compared. In all lesions D2-40 labeled only the
      endothelium of thin-walled vascular channels morphologically consistent with
      lymphatic vessels (25 of 25). No staining of the vascular lesions (0 of 11) or of
      arteries and veins (0 of 25) was observed. All lymphatic lesions had D2-40
      positive vessels; however, the percentage of vessels that stained varied. Five
      lymphatic lesions showed more than 75% D2-40-positive channels, 5 lesions had
      approximately 50%, and 4 cases showed fewer than 25% D2-40-positive channels.
      There was a tendency of more consistent D2-40 staining of small versus large
      lymphatic channels. CD31 constantly labeled arteries, veins, capillaries, and
      lymphatics in all lesions and all endothelial cells in the vascular lesions. D2
      40 is a very specific antibody for lymphatic endothelium, with variable
      sensitivity. CD31 more reliably identifies lymphatic endothelium. Currently, D2
      40 appears to be a good marker to identify lymphatic vessels in pediatric
      vascular tumors and malformations.

PMID- 15719203
TI  - Primary cutaneous CD30-positive anaplastic large cell lymphoma in childhood:
      report of 4 cases and review of the literature.
AB  - We present the clinicopathologic findings in 4 children with primary cutaneous
      anaplastic large cell lymphoma (C-ALCL). The patients ranged in age from 13
      months to 8 years, with 3 females and 1 male. All presented with a rapidly
      enlarging mass involving the skin and subcutaneous tissue. Histologic evaluation
      showed sheets of large pleomorphic lymphoid cells that were diffusely and
      strongly CD30(+). Tumor cells were CD45(+) in 1 of 4 cases. Cells were of T-cell
      phenotype, with variable positivity for CD3 (3 of 4 cases) and CD5 (2 of 4
      cases). All 4 cases were positive for CD4 and clusterin. Staining for anaplastic
      lymphoma kinase was negative in all cases. No evidence of systemic involvement
      was noted at initial presentation or over a follow-up of 5 to 78 months, although
      3 patients had cutaneous recurrences. Primary C-ALCL has only rarely been
      described in the pediatric population. The high-grade histologic appearance of
      this lymphoma belies its generally favorable clinical course and prognosis.
      Recognition of this entity and its differentiation from other T-cell lymphomas
      that secondarily involve the skin is important to avoid unnecessarily aggressive
      therapy in these children.

PMID- 15719204
TI  - Unusual case of mesenteric venous thrombosis associated with oral contraceptive
      use in an adolescent girl.
AB  - A 16-year-old girl presented with hematochezia and abdominal pain. The patient
      developed a small bowel obstruction that required a laparotomy, which showed a
      segment of grossly infarcted small bowel with 3 perforations, localized
      abscesses, and creeping fat. Resection and an end-to-end anastomosis were
      performed. Pathologic examination showed underlying mesenteric venous thrombosis
      with no evidence of Crohn's disease. Hematology workup showed no evidence of a
      congenitally inherent hypercoagulable state. The use of oral contraceptives was
      the only predisposing factor identified.

PMID- 15719205
TI  - USCAP Specialty Conference: case 1-type I pleuropulmonary blastoma.
AB  - Pleuropulmonary blastoma (PPB) was defined in 1988 by Manivel et al. in a series
      describing 11 intrathoracic pulmonary neoplasms in young children. The PPB is a
      unique peripheral pulmonary or pleural-based tumor of childhood that is
      characterized in its earliest form as a bland-appearing multiloculated cyst with
      small foci of tumor cells and in later forms as mixed and predominantly
      primitive, overtly malignant neoplasms. Prior to the introduction of the PPB as a
      distinct entity, this tumor had been reported in the literature as pulmonary
      blastoma, sarcoma arising in mesenchymal cystic hamartoma, embryonal sarcoma,
      malignant mesenchymoma, primary pulmonary rhabdomyosarcoma and rhabdomyosarcoma
      arising in congenital adenomatoid malformation or bronchogenic cyst. Over the
      past 15 years, PPB has come to be recognized in centers around the world. With
      the establishment of the Pleuropulmonary Blastoma Registry by Jack Priest, MD,
      and colleagues, there has been improved understanding of this rare pediatric
      neoplasm.

PMID- 15719207
TI  - Reduced fracture risk in users of thiazide diuretics.
AB  - Thiazide diuretics (TD) reduce renal calcium excretion and may increase bone
      mineral density. A reduced fracture risk has been reported in some but not all
      studies. The aim of this study was to assess fracture risk in users of TD. The
      study design was nationwide population-based pharmacoepidemiological case-control
      study with fracture in year 2000 as outcome and use of TD during the previous 5
      years as the exposure variable. Individual use of TD was derived from the Danish
      National Pharmacological Database and related to fracture data from the National
      Hospital Discharge Register. These data were combined with information on use of
      other drugs, social status, working status, income, educational status, contacts
      with general practitioners and practicing specialists, and comorbidity. A total
      of 64,699 patients (age = 40 years) who sustained a fracture during the year 2000
      were compared to 194,111 age- and gender-matched controls. After adjustment for
      potential confounders, current use of TD was associated with a 10% (95%
      confidence interval [CI], 7% to 12%) reduced risk of any fracture and a 17% (95%
      CI 11% to 23%) reduced risk of forearm fractures. In former TD users, the risk
      reduction was slightly less pronounced. Similar results were found in men and
      women, and in subjects younger or > or = 65 years of age. Dose-effect analysis
      revealed a decreased risk of any fracture and fractures at the forearm and hip
      with an increased number of redeemed defined daily dosages (DDDs) of TD.
      Therefore, use of more than 2000 DDD was associated with a 19% (95% CI 10% to
      27%) decreased hip fracture risk. We conclude that use of TD is associated with a
      significantly reduced fracture risk.

PMID- 15719206
TI  - Hamartoma involving the pseudarthrosis site in patients with neurofibromatosis
      type 1.
AB  - Congenital pseudarthrosis is a rare disease with variable clinical effects. The
      disease remains 1 of the most controversial pediatric entities in terms of
      etiopathogenesis, therapy, and prognosis. Between 0.5% and 2.2% of patients with
      neurofibromatosis demonstrate pseudarthrosis in any of the long bones. The exact
      origin of the lesion is even unclear; although several attempts have been made to
      determine the type of tissue involving the pseudarthrosis site, only fibrous
      tissue has been documented in different reports. We present 2 unrelated Mexican
      patients (male and female) with familial neurofibromatosis and congenital
      pseudarthrosis of the tibia and fibula. Histochemical and immunostain studies
      after surgical resection of the affected ends from the pseudarthrosis site of
      both patients showed a picture compatible with hamartoma. This is the first time
      when histologic evidence of hamartomatous tissue involving the pseudarthrosis
      site is presented.

PMID- 15719209
TI  - Functional anorectal imaging.

PMID- 15719210
TI  - [Extensive, painful erosion of the vulva. Extramammary Paget disease].

PMID- 15719211
TI  - Inheritance and genetic mapping of tuber eye depth in cultivated diploid
      potatoes.
AB  - Tuber eye depth of the potato (Solanum tuberosum L.) is an important trait for
      the processing quality and appearance of potatoes. In the present study, we used
      a cultivated diploid potato family (12601) of 107 plants to dissect the mode of
      inheritance and to map the gene(s) controlling the trait. The family segregated
      for both eye depth (deep vs shallow) and tuber shape (round vs long) traits. The
      deep eye (Eyd) phenotype was found to be associated with round tubers (Ro) in
      most progeny clones. Further evaluation of this population with molecular markers
      including simple sequence repeats, amplified fragment length polymorphism, and
      sequence-characterized amplified regions revealed that the primary locus for eye
      depth is located on chromosome 10. This map location was confirmed by evaluating
      a second diploid family (12586). The results of this study led to the following
      conclusions: (1) there is a major locus controlling the eye depth trait; (2) deep
      eye (Eyd) is dominant to shallow (eyd); (3) the Eyd/eyd locus is located on
      chromosome 10; and (4) the Eyd/eyd locus is closely linked with the major locus
      for tuber shape (Ro/ro), at a distance of about 4 cM.

PMID- 15719212
TI  - A high-density genetic map of hexaploid wheat (Triticum aestivum L.) from the
      cross Chinese Spring x SQ1 and its use to compare QTLs for grain yield across a
      range of environments.
AB  - A population of 96 doubled haploid lines (DHLs) was prepared from F1 plants of
      the hexaploid wheat cross Chinese Spring x SQ1 (a high abscisic acid-expressing
      breeding line) and was mapped with 567 RFLP, AFLP, SSR, morphological and
      biochemical markers covering all 21 chromosomes, with a total map length of 3,522
      cM. Although the map lengths for each genome were very similar, the D genome had
      only half the markers of the other two genomes. The map was used to identify
      quantitative trait loci (QTLs) for yield and yield components from a combination
      of 24 site x treatment x year combinations, including nutrient stress, drought
      stress and salt stress treatments. Although yield QTLs were widely distributed
      around the genome, 17 clusters of yield QTLs from five or more trials were
      identified: two on group 1 chromosomes, one each on group 2 and group 3, five on
      group 4, four on group 5, one on group 6 and three on group 7. The strongest
      yield QTL effects were on chromosomes 7AL and 7BL, due mainly to variation in
      grain numbers per ear. Three of the yield QTL clusters were largely site
      specific, while four clusters were largely associated with one or other of the
      stress treatments. Three of the yield QTL clusters were coincident with the
      dwarfing gene Rht-B1 on 4BS and with the vernalisation genes Vrn-A1 on 5AL and
      Vrn-D1 on 5DL. Yields of each DHL were calculated for trial mean yields of 6 g
      plant(-1) and 2 g plant(-1) (equivalent to about 8 t ha(-1) and 2.5 t ha(-1),
      respectively), representing optimum and moderately stressed conditions. Analyses
      of these yield estimates using interval mapping confirmed the group-7 effects on
      yield and, at 2 g plant(-1), identified two additional major yield QTLs on
      chromosomes 1D and 5A. Many of the yield QTL clusters corresponded with QTLs
      already reported in wheat and, on the basis of comparative genetics, also in
      rice. The implications of these results for improving wheat yield stability are
      discussed.

PMID- 15719214
TI  - Prefrontal TMS produces smaller EEG responses than motor-cortex TMS: implications
      for rTMS treatment in depression.
AB  - RATIONALE: The stimulus intensity of prefrontal repetitive transcranial magnetic
      stimulation (rTMS) during depression treatment is usually determined by adjusting
      it with respect to the motor threshold (MT). There is some evidence that
      reactivity of the prefrontal cortex to transcranial magnetic stimulation (TMS) is
      lower than that of the motor cortex at MT stimulation. However, it is unknown
      whether this is true when other stimulus intensities are used. We investigated
      whether the magnitude and shape of the overall TMS-evoked electroencephalographic
      (EEG) responses differ between prefrontal and motor cortices. METHODS: Magnetic
      pulses to the left motor and prefrontal cortices (the middle frontal gyrus
      identified from magnetic resonance images) were delivered at four intensities
      (60, 80, 100, and 120% of MT of the right abductor digiti minimi muscle) for six
      subjects. Simultaneously, EEG was recorded with 60 scalp electrodes. RESULTS:
      Global mean-field amplitudes (GMFAs) reflecting overall cortical activity were
      significantly smaller after prefrontal- than after motor-cortex TMS. A
      significant positive correlation (r (s)=0.84, p<0.01) was found between GMFAs of
      motor- and prefrontal-cortex TMS across the experiments. However, when
      correlation between the responses of motor and prefrontal cortices was examined,
      significant positive correlations were found at 80 and 100% intensities only.
      CONCLUSIONS: This study provides further evidence that the prefrontal and motor
      cortices have different reactivity to TMS, but the MT may be used for determining
      the stimulus intensity of prefrontal rTMS treatment in depression, at least at
      motor threshold intensities or near to it.

PMID- 15719213
TI  - Chronic coadministration of olanzapine and fluoxetine activates locus coeruleus
      neurons in rats: implications for bipolar disorder.
AB  - RATIONALE: The depressive phase of bipolar disorder (bipolar depression) is a
      difficult-to-treat form of depression. The olanzapine/fluoxetine combination
      (Symbyax) is the only medication approved to treat this disorder. The precise
      neural mechanisms responsible for its efficacy are not clearly understood.
      OBJECTIVES: In order to further elucidate the neurobiological mechanisms
      responsible for the beneficial clinical effects of the olanzapine/fluoxetine
      combination, the current experiment was designed to investigate the effects of
      chronic coadministration of olanzapine and fluoxetine on electrophysiological
      activity in the locus coeruleus (LC). METHODS: Rats received olanzapine for 3
      weeks via subcutaneous osmotic pumps while simultaneously receiving daily
      intraperitoneal injections of fluoxetine. These chronically treated rats were
      anesthetized, and single-unit recordings of LC neurons were made. RESULTS:
      Chronic administration of olanzapine alone significantly increased firing of LC
      neurons, while, as reported previously, chronic administration of fluoxetine
      alone significantly reduced firing of LC neurons. However, in the combination
      condition, olanzapine was able to block the fluoxetine-induced suppression of the
      LC, and a significant increase in LC activity was observed. CONCLUSIONS: The
      observed increase in firing of LC neurons could lead to enhanced levels of
      norepinephrine release in projection areas and amelioration of the clinical
      symptoms of bipolar depression.

PMID- 15719215
TI  - The anti-inflammatory prostaglandin 15d-PGJ2 decreases oxidative/nitrosative
      mediators in brain after acute stress in rats.
AB  - RATIONALE: Immobilisation stress is followed by accumulation of
      oxidative/nitrosative mediators in brain after the release of tumour necrosis
      factor-alpha (TNFalpha) and other cytokines, nuclear factor kappa B (NFkappaB)
      activation, nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2)
      expression in the brain. OBJECTIVES: This study was conducted to assess if some
      of the anti-inflammatory products of COX can modify the accumulation of
      oxidative/nitrosative species seen in brain after stress and to study the
      mechanisms by which this effect is achieved. METHODS: Young-adult male Wistar
      rats were subjected to a single session of immobilisation during 6 h. RESULTS: In
      stressed animals, brain levels of the anti-inflammatory 15d-PGJ2 increases
      concomitantly with COX-2 expression. Inhibition of COX-2 with NS-398 prevents
      stress-induced 15d-PGJ2 increase. Injection of supraphysiological doses of 15d
      PGJ2 (80-120 microg/kg) decreases stress-induced increase in NOS-2 activity as
      well as the stress-induced increase in NO metabolites. On the other hand, 15d
      PGJ2 decreases stress-induced malondialdehyde (an indicator of lipid
      peroxidation) accumulation in cortex and prevents oxidation of the main anti
      oxidant glutathione. The mechanisms involved in the anti-oxidative properties of
      15d-PGJ2 in stress involve NFkappaB blockade (by preventing stress-induced
      IkappaBalpha decrease) as well as inhibition of TNFalpha release in stressed
      animals. At the doses tested, 15d-PGJ2 decreases COX-2 expression and PGE2
      release during stress, suggesting an alternative mechanism for this endogenous
      compound. CONCLUSIONS: These findings demonstrate a role for this anti
      inflammatory pathway in the brain response to stress and open the possibility for
      preventing accumulation of oxidative/nitrosative species and subsequent brain
      damage.

PMID- 15719217
TI  - Influence of inflammatory nociception on the anxiolytic-like effect of diazepam
      and buspirone in rats.
AB  - RATIONALE: The effect of anxiety on nociception has been evaluated but not that
      of nociception on anxiety. OBJECTIVE: The study was conducted to analyse the
      influence of nociception on basal levels of anxiety-like behaviour and on the
      action of anxiolytic drugs. METHODS: Nociception was induced by an intra
      articular injection of uric acid at 3.75 or 7.5%. Experimental anxiety was
      determined in the rat burying behaviour and the elevated plus maze tests. To
      separate specific anxiety-related drug actions, a spontaneous ambulatory test was
      included. The anxiolytics, buspirone (2.5 and 5.0 mg/kg, i.p.) and diazepam (0.5,
      1.0 and 2.0 mg/kg, i.p.), were used. RESULTS: In the nociception test, the pain
      induced functional impairment rat model, uric acid at 3.75 and 7.5% had an effect
      of around 35 and 75%, respectively. Uric acid (UA) at the lower dose (3.75%)
      lacked an effect on burying behaviour but significantly increased the time spent
      and number of entries to the open arms; the higher UA dose (7.5%) produced a
      significant increase in the time spent and number of entries to the open arms and
      a statistically significant reduction in cumulative burying. Diazepam and
      buspirone produced a clear dose-dependent reduction in cumulative burying. In the
      plus maze, diazepam also induced an increase in the time spent and number of
      entries to the open arms. In the burying behaviour test, rats with a mild level
      of nociception (uric acid at 7.5%) were insensitive to the anxiolytic-like effect
      of these anxiolytic drugs. In the plus maze test, the anxiolytic-like effect of
      diazepam (1.0 mg/kg) was blocked under both levels of nociception. CONCLUSIONS:
      These data demonstrate that nociception modifies the response to anxiolytic
      drugs. The role of factors with anxiogenic properties produced during
      inflammation, which may modify diazepam and buspirone effects, is discussed.

PMID- 15719216
TI  - Yohimbine disrupts prepulse inhibition in rats via action at 5-HT1A receptors,
      not alpha2-adrenoceptors.
AB  - RATIONALE: Prepulse inhibition (PPI) of the acoustic startle response is an
      operational measure of sensorimotor gating that can be assessed in both humans
      and animals. The noradrenergic system appears to play a role in PPI as the alpha1
      agonist cirazoline disrupts PPI and the alpha1 antagonist prazosin blocks the
      disruptions in PPI produced by phencyclidine. OBJECTIVES: To better understand
      the role of adrenergic receptors in the modulation of PPI, we assessed the
      effects of the alpha2 adrenergic antagonist yohimbine (2.5, 5.0, and 7.5 mg/kg)
      on PPI. RESULTS: Yohimbine reduced PPI at the 5.0 and 7.5 mg/kg doses, without
      significantly affecting startle magnitude. In separate experiments, we examined
      whether adrenergic or serotonergic compounds blocked this disruption in PPI
      produced by yohimbine. There was a trend for the alpha2 agonist clonidine (0.01,
      0.02 mg/kg) to attenuate the PPI disruption produced by yohimbine. However, other
      alpha2 agonists (guanfacine, medetomidine) and an alpha1 antagonist (prazosin)
      failed to prevent the disruption. The alpha2 antagonist atipamezole weakly
      decreased PPI in a narrow dose range (0.3-1.0 mg/kg). The 5-HT1A antagonist
      WAY100,635 (0.1, 0.3 mg/kg) significantly prevented the yohimbine-induced
      disruption of PPI. CONCLUSIONS: These findings indicate that (1) yohimbine
      disrupts PPI in rats and (2) the yohimbine-induced disruption of PPI is largely
      due to the 5-HT1A partial agonist properties of yohimbine.

PMID- 15719218
TI  - Topiramate does not alter expression in rat brain of enzymes of arachidonic acid
      metabolism.
AB  - RATIONALE: When administered chronically to rats, drugs that are effective in
      bipolar disorder-lithium and the anticonvulsants, valproic acid and carbamazepine
      have been shown to downregulate the expression of certain enzymes involved in
      brain arachidonic acid (AA) release and cyclooxygenase (COX)-mediated metabolism.
      Phase II clinical trials with the anticonvulsant topiramate [2,3:4,5-bis-O-(1
      methylethylidene)-beta-D-fructopyranose sulfamate] suggest that this drug may
      also be effective for bipolar disorder. OBJECTIVES: To see if topiramate has
      effects similar to those of the other three drugs, we administered topiramate to
      rats for 14 days at 20 mg/kg, p.o. twice daily. RESULTS: Compared with p.o.
      vehicle, topiramate treatment did not significantly affect the brain activity or
      protein level of cytosolic phospholipase A2, secretory PLA2, or Ca2+-independent
      iPLA2. Additionally, brain protein levels of COX-1, COX-2, 5-lipoxygenase, and
      cytochrome P450 epoxygenase were unchanged. CONCLUSIONS: These results suggest
      that topiramate does not modify expression of the enzymes involved in brain AA
      metabolism that have been shown to be targeted by lithium, valproic acid, or
      carbamazepine. If topiramate proves effective in bipolar disorder, it may not act
      by modulating brain AA metabolism. In view of the proven anticonvulsant effect of
      topiramate, our results also suggest that the AA cascade is not involved in the
      anti-seizure properties of the drug.

PMID- 15719219
TI  - Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced
      facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine.
AB  - RATIONALE: Chronic treatment with selective serotonin reuptake inhibitors (SSRIs)
      can delay ejaculation in humans, but the extent of this effect differs between
      SSRIs. The involvement of 5-HT1A receptors is likely, since 5-HT1A receptor
      agonists accelerate ejaculation and chronic SSRI treatment is thought to
      desensitize 5-HT1A receptors. OBJECTIVES: This study was conducted to examine the
      effects of chronic pretreatment with the SSRIs fluvoxamine and paroxetine on the
      facilitation of ejaculation induced by the 5-HT1A receptor agonist 8-OH-DPAT.
      METHODS: Sexually experienced Wistar rats with normal ejaculatory behavior were
      treated for 22 days with vehicle, fluvoxamine (30 mg/kg/day), or paroxetine (10
      or 20 mg/kg/day, p.o.). On day 22, rats received a challenge with saline or 8-OH
      DPAT (0.4 mg/kg, s.c.). Sexual behavior was tested on days 1, 8, 15, and 22 of
      the SSRI-treatment. RESULTS: Treatment with both doses of paroxetine, but not
      fluvoxamine, delayed ejaculation. 8-OH-DPAT strongly accelerated ejaculation
      under vehicle conditions. Pretreatment with paroxetine reduced the effects of 8
      OH-DPAT on ejaculation in a dose-dependent manner and more strongly than
      fluvoxamine. CONCLUSIONS: SSRIs affect 5-HT1A receptors involved in ejaculation.
      The degree to which this occurs, with paroxetine exerting a stronger effect than
      fluvoxamine, might determine the extent of SSRI-induced delayed ejaculation.

PMID- 15719221
TI  - Characterization of conditioned place preference to cocaine in congenic dopamine
      transporter knockout female mice.
AB  - RATIONALE: The dopamine transporter (DAT) is thought to play a major role in the
      rewarding effects of cocaine. Therefore, it is surprising that cocaine reveals
      conditioned effects in DAT knockout (DAT-KO) mice. OBJECTIVES: To examine these
      findings further, we obtained complete dose-effect curves for DAT-KO and DAT wild
      type (DAT-WT) mice in a cocaine conditioned place preference (CPP) procedure.
      METHODS: Congenic C57BL6 background female DAT-KO and DAT-WT mice were
      conditioned in a three-compartment place preference apparatus. Conditioning
      consisted of three 30-min sessions with cocaine (2.5, 5.0, 10.0, 20.0, or 40.0
      mg/kg) and three 30-min sessions with saline. The distribution of time in each
      choice compartment was determined after each pair of conditioning sessions (one
      cocaine and one saline session). RESULTS: DAT-WT mice revealed CPP over a wide
      range of cocaine doses (5.0-40 mg/kg), whereas DAT-KO mice revealed CPP over a
      more restricted range of doses, with consistent CPP only occurring with 10 mg/kg
      of cocaine. CONCLUSIONS: CPP for cocaine develops in both DAT-KO and DAT-WT mice;
      however, the dose range at which CPP develops is much more restricted in DAT-KO
      mice than in DAT-WT mice. These observations corroborate the significant role of
      DAT inhibition in cocaine's conditioned effects.

PMID- 15719220
TI  - Subtle effects of ketamine on memory when administered following stimulus
      presentation.
AB  - RATIONALE: N-methyl-D-aspartate (NMDA) receptor antagonists (e.g., PCP, ketamine)
      have been shown to impair learning/memory. Well documented in animal models, only
      limited research in humans has been reported. Findings to date are similar to
      results of animal studies; however, antagonists are typically administered before
      the learning experience. This may be problematic as memory failure could be
      secondary to inattention induced by the psychotomimetic effects of these drugs
      and/or alterations in sensory processing which can degrade the quality of the
      stimulus, thereby affecting the accuracy of recall. OBJECTIVE: The objective of
      the study is to compare the effects of ketamine vs placebo on recall for words
      when administered after stimulus presentation. METHODS: In this double-blind
      crossover study, 24 normal controls were given bolus injections of ketamine (0.3
      mg/kg) or placebo. Immediately prior to infusion, subjects were administered a
      verbal memory test. Delayed recall was measured 45 min postinfusion. Mental
      status changes were assessed using the Brief Psychiatric Rating Scale. RESULTS:
      Subjects experienced a significant increase in psychiatric symptoms that peaked
      at 20 min. Results indicate no differences between the drug and placebo
      conditions for the memory task. However, reminiscence (i.e., recall of previously
      unrecalled items with repeated testing) was significantly reduced following
      ketamine administration compared to placebo. CONCLUSIONS: Findings suggest that
      aspects of memory consolidation are affected by drugs that interfere with NMDA
      receptor function.

PMID- 15719222
TI  - Bidirectional effects of benzodiazepine binding site ligands on active avoidance
      acquisition and retention: differential antagonism by flumazenil and beta-CCt.
AB  - RATIONALE: The pharmacological approach, using subtype selective ligands,
      complements genetic studies on the specific contribution of individual receptor
      subtypes to the various effects of benzodiazepines. OBJECTIVE: The aim of this
      study was to examine the relative significance of alpha1-containing GABA(A)
      receptors in the effects of modulators at the benzodiazepine site on anxiety and
      memory processes. METHODS: We tested the effects of the nonselective antagonist
      flumazenil, the preferential alpha1-subunit selective antagonist beta-carboline-3
      carboxylate-t-butyl ester (beta-CCt), the nonselective agonist midazolam, the
      preferential alpha1-subunit selective agonist zolpidem, and the nonselective
      inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM)
      in a two-way active avoidance task in rats. The influence of flumazenil (10.0
      mg/kg) and beta-CCt (30.0 mg/kg) on the effects of the two agonists were also
      examined. In the schedule 2 x 30 trials, drugs were administered i.p. 20 min
      before the training session. Avoidance responses in the training session are an
      anxiety-mediated behavior, whereas performance in the retention session relates
      to the effects on memory. RESULTS: Flumazenil and beta-CCt did not affect
      behavior. Midazolam (2.0 mg/kg) facilitated acquisition performance, while DMCM
      (1.0 and 2.0 mg/kg) induced the opposite effect. Flumazenil antagonized both
      effects. Beta-CCt potentiated the effect of midazolam, and partly antagonized the
      effect of DMCM. Midazolam (0.5 and 1.0 mg/kg) and zolpidem (1.0-3.0 mg/kg)
      impaired, while DMCM (0.1 mg/kg) facilitated the subjects' performance in the
      retention test. The amnesic effects were attenuated but not fully reversed, while
      the effect of DMCM was counteracted by both antagonists. CONCLUSION: The results
      indicate the alpha1-subunit interferes with the anxiolytic effect of a
      benzodiazepine site agonist and may contribute to the DMCM-induced anxiogenic
      effect. It is also substantially involved in the bidirectional memory processing
      in the active avoidance paradigm.

PMID- 15719223
TI  - Evaluation of GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one
      as a neurobiological substrate for the anti-anxiety effect of ethanol in rats.
AB  - RATIONALE: Acute systemic ethanol administration is known to elevate plasma and
      cerebral levels of neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one
      (3alpha, 5alpha-THP; allopregnanolone) to a concentration sufficient to
      potentiate GABA(A) receptors. We have earlier demonstrated that 3alpha, 5alpha
      THP mediates the antidepressant-like effect of ethanol in Porsolt forced swim
      test. OBJECTIVE: The aim of the present study is to explain the relationship
      between endogenous GABAergic neurosteroids and anxiolytic effect of ethanol in
      Sprague-Dawley rats. METHOD: The mediation of 3alpha, 5alpha-THP in the anti
      anxiety effect of ethanol was assessed by pharmacological interactions of ethanol
      with various endogenous neurosteroidal modulators and using simulated
      physiological conditions of altered neurosteroid content in elevated plus maze
      (EPM) test. RESULTS: Pretreatment of 3alpha, 5alpha-THP (0.5-2.5 mug/rat, i.c.v.)
      or neurosteroidogenic agents such as 3alpha, 5alpha-THP precursor progesterone (5
      or 10 mg/kg, i.p.), 11-beta hydroxylase inhibitor metyrapone (50 or 100 mg/kg,
      i.p.) or the GABA(A) receptor agonist muscimol (25 ng/rat, i.c.v.) significantly
      potentiated the anti-anxiety effect of ethanol (1 g/kg, i.p.). On the other hand,
      the GABAergic antagonistic neurosteroid dehydroepiandrosterone sulphate (DHEAS)
      (1 mg/kg, i.p.), the GABA(A) receptor blocker bicuculline (1 mg/kg, i.p.), the
      5alpha-reductase inhibitor finasteride (50 x 2 mg/kg, s.c.) or the mitochondrial
      diazepam binding inhibitory receptor antagonist PK11195 (1 mg/kg, i.p.) reduced
      ethanol-induced preference of time spent and number of entries into open arms.
      Anti-anxiety effect of ethanol was abolished in adrenalectomized (ADX) rats as
      compared to sham-operated control. This ADX-induced blockade was restored by
      prior systemic injection of progesterone, signifying the contribution of
      peripheral steroidogenesis in ethanol anxiolysis. Socially isolated animals known
      to exhibit decreased brain 3alpha, 5alpha-THP and GABA(A) receptor functions
      displayed reduced sensitivity to the effects of ethanol and 3alpha, 5alpha-THP in
      EPM test. CONCLUSIONS: Our results demonstrated the contributory role of
      neuroactive steroid 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol. It
      is speculated that ethanol-induced modulation of endogenous GABAergic
      neurosteroids, especially 3alpha, 5alpha-THP, might be crucial pertinent to the
      etiology of 'trait' anxiety (tension reduction) and ethanol abuse.

PMID- 15719224
TI  - Reduced nicotine reward in obesity: cross-comparison in human and mouse.
AB  - RATIONALE: Tobacco use and obesity lead to significant morbidity and mortality.
      OBJECTIVE: This study was conducted to investigate the factors maintaining
      smoking behavior in lean and obese individuals by utilizing a mouse/human cross
      validation model of nicotine reward. METHODS: In humans, a cigarette choice
      paradigm was used to examine the relative reinforcing value of nicotine in obese
      and non-obese smokers. Conditioned place preference (CPP) for nicotine was
      assessed in mice fed standard low fat rodent chow and mice rendered obese by a
      high fat diet. RESULTS: In humans, obese smokers self-administered nicotine via
      cigarettes significantly less often than non-obese smokers and showed attenuated
      hedonic effects of nicotine-containing cigarettes compared to denicotinized
      cigarettes. Similarly, mice exposed to a high fat diet did not exhibit nicotine
      CPP, relative to control mice. mRNA levels for mu-opiate and leptin receptors
      were also downregulated in the ventral tegmental area of these mice. CONCLUSIONS:
      Together, these studies provide the first evidence for reduced nicotine reward in
      obese subjects and suggest that this may be mediated by dietary influences on the
      endogenous opioid system.

PMID- 15719225
TI  - HS014, a selective melanocortin-4 (MC4) receptor antagonist, modulates the
      behavioral effects of morphine in mice.
AB  - RATIONALE: Melanocortin and opioid systems regulate feeding as well as other
      behaviors; however, the relationship between the two systems is not yet defined.
      Since agonist-induced stimulation of melanocortin receptors blocks the behavioral
      effects of mu opioid receptor agonists, and melanocortin-4 (MC4) receptors and mu
      opioid receptors share a similar anatomical distribution in the central nervous
      system, MC4 receptor blockade may increase opioid responsiveness. OBJECTIVES: The
      goal of this study was to test the hypothesis that blockade of MC4 receptors
      increases the behavioral effects of morphine. METHODS: The effects of HS014
      (0.0032, 0.032, and 1 nmol, i.c.v.), a selective MC4 antagonist, on morphine
      induced (3.2, 10, and 32 mg/kg, i.p.) locomotor activity (measured in the open
      field for 15 min) and antinociception (measured in the hot plate at 55 degrees C)
      were assessed in C57Bl/6 mice. In addition, the effects of morphine were
      evaluated in A(y) mice, a genetic model for MC4 receptor blockade. RESULTS: The
      dose-effect curve of morphine for locomotor activity was shifted downwards in
      C57Bl/6 mice pretreated with HS014 and in A(y) mice. The dose-effect curve of
      morphine for antinociception was shifted two- and threefold to the left in
      C57Bl/6 mice pretreated with HS014 and in A(y) mice, respectively. CONCLUSIONS:
      These results indicate that blockade of MC4 receptors increases the
      antinociceptive effects of morphine without changing the potency of morphine for
      locomotor activity, suggesting that MC4 receptor antagonists may be candidate
      drugs that can be clinically used for the treatment of pain.

PMID- 15719226
TI  - Non-uniform blockade of intrastriatal D2/D3 receptors by risperidone and
      amisulpride.
AB  - RATIONALE: Atypical antipsychotic drugs have been shown to preferentially affect
      extrastriatal (mesolimbic) D2/D3 receptors over those within the striatum
      (nigrostriatal). The striatum does not contain exclusively nigrostriatal dopamine
      tracts, however. The caudate nucleus and ventral parts of the striatum primarily
      contain limbic and associative dopamine pathways more relevant to psychosis.
      OBJECTIVES: We tested the hypothesis that two pharmacologically distinct atypical
      antipsychotic drugs, amisulpride and risperidone, would preferentially occupy of
      D2/D3 dopamine receptors in limbic and associative regions of the striatum.
      METHODS: Eight amisulpride-treated patients, six risperidone-treated patients and
      six age- and sex-matched healthy controls were recruited. Dynamic SPET studies
      were performed after bolus injection of [123I]epidepride. Binding potential (BP)
      images were generated using a modified Logan method and aligned between subjects.
      Regions of interest (ROIs) were placed around head of caudate and putamen
      bilaterally on an average BP map derived from aligned control images. These ROIs
      were then applied user-independently to the BP maps for each subject to calculate
      BP for head of caudate and putamen. Mean occupancy of D2/D3 receptors in each ROI
      was determined by reference to the drug-free healthy volunteer group. Occupancy
      values for head of caudate and putamen were compared using paired Student's t
      test. RESULTS: D2/D3 receptor occupancy was 42% in caudate and 31% in putamen for
      risperidone (t=5.9, df=11, p=0.0001) and 51% in caudate and 37% in putamen for
      amisulpride (t=11.1, df=15, p<0.0001). CONCLUSIONS: Amisulpride and risperidone
      both show selective occupancy for limbic and associative D2/D3 receptors within
      the striatum.

PMID- 15719227
TI  - Neuropeptide expression in rats exposed to chronic mild stresses.
AB  - To investigate a possible link between some neuropeptides and depression, we
      analyzed their mRNA levels in brains of rats exposed to chronic mild stresses
      (CMS; a stress-induced anhedonia model), a commonly used model of depression.
      Rats exposed for 3 weeks to repeated, unpredictable, mild stressors exhibited an
      increased self-stimulation threshold, reflecting the development of an anhedonic
      state, which is regarded as an animal model of major depression. In situ
      hybridization was employed to monitor mRNA levels of neuropeptide Y (NPY),
      substance P and galanin in several brain regions. In the CMS rats, NPY mRNA
      expression levels were significantly decreased in the hippocampal dentate gyrus
      but increased in the arcuate nucleus. The substance P mRNA levels were increased
      in the anterodorsal part of the medial amygdaloid nucleus, in the ventromedial
      and dorsomedial hypothalamic nuclei and the lateral hypothalamic area, whereas
      galanin mRNA levels were decreased in the latter two regions. These findings
      suggest a possible involvement of these three peptides in mechanisms underlying
      depressive disorders and show that similar peptide changes previously
      demonstrated in genetic rat models also occur in the present stress-induced
      anhedonia model.

PMID- 15719229
TI  - Agonist diversity in 5-HT(2C) receptor-mediated weight control in rats.
AB  - RATIONALE: Food intake and energy expenditure are the two main determinants of
      body weight. Given that 5-HT(2C) receptor agonists are reported to have effects
      on both energy expenditure and food intake, this strongly suggests that 5-HT(2C)
      receptor agonists have excellent potential for development as antiobesitiy drugs.
      One important issue in antiobesity drug development is whether the effects of the
      compound are maintained during chronic drug treatment. OBJECTIVES: The purpose of
      the present study was to investigate the effect of repeated oral administration
      of three 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP), d(S)-2-(6
      chloro-5-fluoroindol-1-yl)-1-methylethylamine (RO60-0175) and (S)-2-(7-ethyl-1H
      furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348), on food intake and energy
      expenditure in rats. RESULTS: In the food intake study, mCPP, RO60-0175 and YM348
      decreased food intake in a dose-dependent manner on day 1 of administration. On
      day 14 of repeated administration, the hypophagic effect of YM348 was lost and
      that of mCPP was reduced. In contrast, the hypophagic effect of RO60-0175 was
      maintained even after repeated administration. The hypophagic effects of all
      agonists were significantly inhibited by a 5-HT(2C) receptor antagonist,
      SB242084. In contrast to the hypophagic effects, no drug tolerance developed with
      respect to the hyperthermic effects of mCPP, RO60-0175, and YM348. The
      hyperthermic effects of these drugs were also inhibited by SB242084. CONCLUSIONS:
      Together, the difference between compounds in their hypophagic effects and the
      similarity in their hyperthermic effects suggest a diversity in agonists in 5
      HT(2C) receptor-mediated weight control in rats.

PMID- 15719228
TI  - Voluntary alcohol intake in two rat lines selectively bred for learned helpless
      and non-helpless behavior.
AB  - RATIONALE: A high comorbidity between depression and alcoholism has been reported
      in several studies, but the mechanisms underlying this relationship remain
      unknown. OBJECTIVES: We tested whether learned helplessness in rats as a model
      for depression is associated with enhanced alcohol intake and relapse behavior.
      METHODS: Congenital learned helplessness (cLH) and congenital non-learned
      helplessness (cNLH) rats were selectively bred for differences in an escape
      paradigm. Sucrose preference was tested at the first hour of the dark phase. In
      order to study an association with alcohol drinking behavior, rats underwent a
      free-choice procedure with access to water, and 5% and 20% alcohol solutions for
      6 weeks. After acquisition of alcohol drinking behavior, the alcohol deprivation
      effect (ADE) was assessed. Sensitivity to the sedative-hypnotic effect of alcohol
      was measured by loss of the righting reflex. RESULTS: cLH rats showed
      significantly lower preference for sucrose solutions during the second half hour
      of the dark phase than cNLH rats. Alcohol intake of male cLH rats was not
      significantly different from that of male cNLH rats. In contrast, cLH female rats
      consumed higher amounts of alcohol than female cNLH rats. The ADE was more
      pronounced in female animals, although the magnitude of the ADE was similar in
      both cNLH and cLH female rats. The time to regain the righting reflex was
      significantly higher in both male and female cLH rats than in cNLH rats.
      CONCLUSIONS: In summary, these data suggest that an inborn depressive-like
      behavior in female rats is associated with enhanced alcohol intake.

PMID- 15719231
TI  - Tolerance to baclofen's sedative effect in alcohol-addicted patients: no
      dissipation after a period of abstinence.

PMID- 15719230
TI  - Differential effects of amphetamine isomers on dopamine release in the rat
      striatum and nucleus accumbens core.
AB  - RATIONALE: Current medications for attention-deficit/hyperactivity disorder
      (ADHD) include some single isomer compounds [dextroamphetamine (D: -amphetamine,
      dexedrine) and dexmethylphenidate (Focalin)] and some racemic compounds
      [methylphenidate and mixed-salts amphetamine (Adderall)]. Adderall, which
      contains approximately 25% L: -amphetamine, has been successfully marketed as a
      first-line medication for ADHD. Although different clinical effects have been
      observed for D: -amphetamine, Adderall, and benzedrine; potential
      psychopharmacological differences on the level of neurotransmission between D: 
      amphetamine and L: -amphetamine have not been well characterized. OBJECTIVES: To
      evaluate potential differences in the isomers, we used the technique of high
      speed chronoamperometry with Nafion-coated single carbon-fiber microelectrodes to
      measure amphetamine-induced release of dopamine (DA) in the striatum and nucleus
      accumbens core of anesthetized male Fischer 344 rats. Amphetamine solutions were
      locally applied by pressure ejection using micropipettes. RESULTS: The presence
      of L: -amphetamine in the D: ,L: -amphetamine solutions did not cause increased
      release of DA but did change DA release kinetics. The D: ,L: -amphetamine-evoked
      signals exhibited significantly faster rise times and shorter signal decay times.
      This difference was also observed in the nucleus accumbens core. When L: 
      amphetamine was locally applied, DA release was not significantly different in
      amplitude, and it exhibited the same rapid kinetics of D: ,L: -amphetamine.
      CONCLUSIONS: These data support the hypothesis that amphetamine isomers have
      different effects on release of DA from nerve endings. It is possible that L: 
      amphetamine may have unique actions on the DA transporter, which is required for
      the effects of amphetamine on DA release from nerve terminals.

PMID- 15719232
TI  - Rapid analysis of pyrethroids in whole urine by high-performance liquid
      chromatography using a monolithic column and off-line preconcentration in a
      restricted access material cartridge.
AB  - A rapid high-performance liquid chromatography (HPLC) method using a monolithic
      column with UV detection at 238 nm was developed for the determination of
      fenpropathrin, betacyfluthrin, deltamethrin, and permethrin (cis and trans
      isomers) in whole urine. The method is based on the use of a monolithic
      chromatographic column and a restricted access material (RAM) cartridge for
      sample preparation. The mobile phase was water/acetonitrile (42:58 v/v), the flow
      rate was 3 mL min(-1), and chromatographic separation was carried out in 10 min.
      The separation of cis and trans isomers of permethrin was also possible under the
      above-mentioned conditions. Detection limits in reconstituted whole urine samples
      were between 0.9 microg L(-1) for betacyfluthrin and 4.4 microg L(-1) for
      fenpropathrin and trans-permethrin. Recoveries for urine samples spiked with
      different amounts of pyrethroids (between 19 microg L(-1) and 75 microg L(-1))
      were in the 70+/-6 to 90+/-7% range.

PMID- 15719233
TI  - Theoretical opportunities and actual limitations of pH gradient HPLC.
AB  - In a series of reports published recently by our laboratory comprehensive theory
      and experimental conditions were established for reversed-phase high-performance
      liquid chromatography (RP HPLC) employing the programmed pH gradient of mobile
      phase. A procedure was developed providing, rapidly and conveniently, the acidity
      (pK(a)) of weak acids and bases and their lipophilicity (hydrophobicity) log
      k(w). The basis of the double-gradient RP HPLC, employing simultaneous gradients
      of organic modifier content and mobile phase pH, was also elaborated. The
      fundamentals of the approach are presented briefly and systematically and its
      advantages and limitations are discussed. It is demonstrated that the newly
      introduced pH gradient method increases the analytical versatility of RP HPLC and
      our understanding of its physicochemical basis.

PMID- 15719234
TI  - Analytical phosphorus fractionation in sewage sludge and sediment samples.
AB  - The Standards, Measurements and Testing (SMT) harmonized procedure for phosphorus
      fractionation in freshwater sediments (SMT protocol), which was developed within
      the framework of the Standards, Measurements and Testing (SMT) Programme of the
      European Commission, has been applied to different environmental samples such as
      sewage sludge, river and marine sediments. The phosphorus contents in the
      extracts were spectrophotometrically determined; the measurement conditions and
      the matrix effects were evaluated for each fraction. The partitioning patterns
      obtained for sewage sludge and sediment samples reveal that the distribution
      between inorganic and organic phosphorus forms is independent of the matrix
      composition of the samples. In addition, a higher available phosphorus content
      was found in sewage sludges due to the higher percentages of labile phosphorus
      forms, which suggests possible internal phosphorus release. Finally, one
      simplified pseudototal microwave digestion method was performed for total
      phosphorus determination which was validated by its application to the reference
      material BCR-684.

PMID- 15719235
TI  - Electrochemical DNA sensing based on gold nanoparticle amplification.
AB  - A hybridization signal-amplified method based on a gold nanoparticle-supported
      DNA sequence for electrochemical DNA sensing has been investigated by cyclic
      voltammetry, differential-pulse voltammetry, and atomic-force microscopy (AFM).
      Quantitative analysis showed that the peak current increment (DeltaIp) is
      linearly dependent on the concentration of the gold nanoparticle-supported DNA
      sequence Au2 over the range 0.51-8.58 pmol L(-1). AFM results indicated that the
      extent of surface hybridization was dependent on the concentration of the gold
      nanoparticle-supported DNA sequence. Moreover, a new pair of peaks, which might
      arise from the special configuration of the gold-nanoparticle-supported DNA
      sequence, appeared in the cyclic voltammogram after hybridization. Although quite
      sensitive, this DNA sensing surface was not easily regenerated, so this kind of
      amplified method was suitable for disposable DNA sensors and chip-based gene
      diagnosis sensors.

PMID- 15719236
TI  - Use of ICP and XAS to determine the enhancement of gold phytoextraction by
      Chilopsis linearis using thiocyanate as a complexing agent.
AB  - Under natural conditions gold has low solubility that reduces its
      bioavailability, a critical factor for phytoextraction. Researchers have found
      that phytoextraction can be improved by using synthetic chelating agents.
      Preliminary studies have shown that desert willow (Chilopsis linearis), a common
      inhabitant of the Chihuahuan Desert, is able to extract gold from a gold-enriched
      medium. The objective of the present study was to determine the ability of
      thiocyanate to enhance the gold-uptake capacity of C. linearis. Seedlings of this
      plant were exposed to the following hydroponics treatment: (1) 5 mg Au L(-1)
      (2.5x10(-5) mol L(-1)), (2) 5 mg Au L(-1) + 10(-5) mol L(-1) NH4SCN, (3) 5 mg Au
      L(-1) + 5x10(-5) mol L(-1) NH4SCN, and (4) 5 mg Au L(-1) + 10(-4) mol L(-1)
      NH4SCN. Each treatment had its respective control. After 2 weeks we determined
      the effect of the treatment on plant growth and gold content by inductively
      coupled plasma-optical emission spectroscopy (ICP-OES). No signs of shoot-growth
      inhibition were observed at any NH4SCN treatment level. The ICP-OES analysis
      showed that addition of 10(-4) mol L(-1) NH4SCN increased the concentration of
      gold by about 595, 396, and 467% in roots, stems, and leaves, respectively. X-ray
      absorption spectroscopy (XAS) studies showed that the oxidation state of gold was
      Au(0) and that gold nanoparticles were formed inside the plants.

PMID- 15719237
TI  - Proline-based modulation of 2,4-diacetylphloroglucinol and viable cell yields in
      cultures of Pseudomonas fluorescens wild-type and over-producing strains.
AB  - The antifungal compound 2,4-diacetylphloroglucinol (DAPG) is produced in the
      rhizosphere of wheat by pseudomonad populations responsible for the natural
      biological control phenomenon known as "take-all decline." Studies were conducted
      to elucidate the impact of DAPG and its co-product 2,4,6-trihydroxyacetophenone
      (THA) on the production of Pseudomonas fluorescens for biological control.
      Increasing DAPG from 0.1 g/l to 0.5 g/l and THA from 0.05 g/l to 0.5 g/l
      significantly inhibited the growth and lowered the yield of viable bacteria in
      liquid cultures. On further examination of these metabolites applied in seed
      coatings, levels of DAPG and THA exceeding 0.05 mg/g seed significantly reduced
      wheat germination percentages. The three-way interaction of DAPG, THA, and
      culture medium ingredients was significant, and greatest seed germination loss
      (40-50%) was observed when 0.5 mg DAPG and 0.25 mg THA were combined in a coating
      of 0.5 ml culture medium per gram of seed. Based on the results of Biolog GN
      microplate, flask, and fermentor screens of C sources, proline was found to
      optimize the viable cell yields of the P. fluorescens strains tested. The
      combination of proline with glucose and urea as C and N sources in growth media
      could be optimized to minimize DAPG production and maximize the vitality of P.
      fluorescens Q8R1-96 and Q69c-80:miniTn5:phl20 (DAPG over-producer). In production
      cultures, the proline supply rate offers a potentially useful means to optimize
      the biological control agent yield and quality.

PMID- 15719238
TI  - Overexpression of a pepper basic pathogenesis-related protein 1 gene in tobacco
      plants enhances resistance to heavy metal and pathogen stresses.
AB  - A pepper gene, CABPR1, which encodes basic pathogenesis-related protein 1, has
      been reported to be strongly induced after ethephon treatment, wounding, and
      tobacco mosaic virus infection. The potential role of CABPR1 in tolerance of
      biotic or abiotic stresses was examined in transgenic Nicotiana tabacum cv.
      xanthi plants. Overexpression of CABPR1 in tobacco plants enhanced tolerance not
      only to heavy metal stresses, but also to the oomycete pathogen Phytophthora
      nicotianae, and the bacterial pathogens Ralstonia solanacearum and Pseudomonas
      syringae pv. tabaci. RT-PCR revealed that the CABPR1 transgene increased
      expression of the PR-Q and glutathione S-transferase genes, but decreased
      expression of the PR-1a and thaumatin genes. Moreover, these transgenic lines
      exhibited significant decreases in total peroxidase activity and transcription
      level, suggesting that overexpression of CABPR1 in tobacco cells altered the
      balance of redox systems. Redox imbalance in transgenic lines may lead to
      H(2)O(2) accumulation, triggering tolerance to biotic and abiotic stresses.

PMID- 15719239
TI  - Dynamic conformational states of DNA containing T.T or BrdU.T mispaired bases:
      wobble H-bond pairing versus cross-strand inter-atomic contacts.
AB  - The dynamic structure of 11-mer DNA duplexes of different sequences with or
      without homopyrimidine (T.T, or BrdU.T) mismatches was studied by molecular
      dynamics (MD) simulations on a time scale from 200 ps to 1 ns. The conformational
      analysis suggests that in mismatched duplexes the formation of classical T.T
      wobble H-bonding pairing is nearest-neighbor sequence-dependent and, in most
      cases, three-centered H-bonds and numerous alternative close cross-strand
      interatomic contacts exist. Thus, in duplex W1, where the central triplet is
      5'd(CTA).d(TTG), two wobble conformations W upward arrow (alphabeta) and W
      downward arrow (betaalpha) are formed and exchange rapidly at 300 K. In contrast,
      when the central triplet is 5'd(TTT).d(ATA) (W2 duplex) wobble conformations are
      rarely observed at 300 K, and the T.T mispair most often adopts a "twisted"
      conformation with one largely persistent normal H-bond, plus a stable cross
      strand contact involving a T flanking base. However, at elevated temperature (400
      K) the same W2 duplex shows frequent exchange between the two classical wobble
      conformations (alphabeta<-->betaalpha), as is in the case when the central
      triplet is 5'd(TBrdUT).d(ATA) (W3 duplex at 300 K). It is suggested that in the
      W2 sequence, restrictions due to thymine-methyl/pi interactions prevent the
      formation of wobble pairing and thermal activation energy, and/or the chemical
      replacement of T by BrdU are required in order for the T(BrdU).T mismatch to
      adopt and exchange between wobble conformations. The specific short and/or long
      lived (double/triple) cross-strand dynamic interactions in W1, W2 and W3 duplexes
      are throughout characterized. These frequent atomic encounters exemplify possible
      inter-strand charge transfer pathways in the studied DNA molecules.

PMID- 15719240
TI  - Watching the best nutcrackers: what capuchin monkeys (Cebus apella) know about
      others' tool-using skills.
AB  - The present work is part of a decade-long study on the spontaneous use of stones
      for cracking hard-shelled nuts by a semi-free-ranging group of brown capuchin
      monkeys (Cebus apella). Nutcracking events are frequently watched by other
      individuals--usually younger, less proficient, and that are well tolerated to the
      point of some scrounging being allowed by the nutcracker. Here we report findings
      showing that the choice of observational targets is an active, non-random
      process, and that observers seem to have some understanding of the relative
      proficiency of their group mates, preferentially watching the more skilled
      nutcrackers, which enhances not only scrounging payoffs, but also social learning
      opportunities.

PMID- 15719241
TI  - Spontaneous ruptured umbilical hernia in a child with hepatic cirrhosis and
      ascites.
AB  - Spontaneous rupture of umbilical hernia is an unusual and rarely reported
      complication in the patient with hepatic cirrhosis and ascites, and it may be
      fatal. A literature search revealed that patients have been managed both
      operatively and nonoperatively for this condition. All of the reported cases in
      the literature were adults with liver disease and ascites. We present a first
      case of spontaneous rupture of an umbilical hernia in a child with cirrhosis and
      ascites, which was managed with primary repair of the hernia.

PMID- 15719242
TI  - Rapid responses of the cupula in the lateral line of ruffe (Gymnocephalus
      cernuus).
AB  - Displacements of cupulae in the supraorbital lateral line canal in ruffe
      (Gymnocephalus cernuus) have been measured using laser interferometry and by
      applying transient as well as sinusoidal fluid stimuli in the lateral line canal.
      The cupular displacement in response to impulses of fluid velocity shows damped
      oscillations at approximately 120 Hz and a relaxation time-constant of 4.4 ms,
      commensurate with a quality factor of approximately 1.8. These values are in
      close agreement with the frequency characteristics determined via sinusoidal
      fluid stimuli, implying that the nonlinearity of cupular dynamics imposed by the
      gating apparatus of the sensory hair cells is limited in the range of cupular
      displacements and velocities measured (100-300 nm; 100-300 microm/s). The
      measurements also show that cupular displacement instantaneously follows the
      initial waveform of transient stimuli. The functional significance of the
      observed cupular dynamics is discussed.

PMID- 15719243
TI  - [New conduct recommendations for physicians cooperating with the pharmaceutical
      industry? The "FS Codex" and its consequences for physicians].

PMID- 15719244
TI  - [Eugen Rehfish--pioneer of modern urodynamics].
AB  - Eugen Rehfisch published two important articles on vesical sphincter function and
      innervation of the bladder in the Archives of Pathologic Anatomy, Physiology and
      Clinical Medicine edited by R. Virchow in 1897 and 1900. A figure from his first
      urodynamic article (1897) became well known in the urodynamic literature. It
      shows the first simultaneous registration of vesical pressure and urinary volume
      in a human. Eugen Rehfisch's ingenious experimental design for examining the
      process of micturition has remained to this day. For this reason, the board of
      the Forum Urodynamicum, a registered society in Germany, named its innovation
      prize donated by the Pfizer company after Eugen Rehfisch. Eugen Rehfisch was born
      in Kempen/Posen on March 6 1862. He studied at the Friedrich Wilhelms University
      in Berlin and at the Bavarian Julius Maximilian University in Wurzburg. From
      approximately 1889, he worked as a physician in Berlin and was a co-worker of
      Leopold Casper (1859-1959) for some time. He performed his important urodynamic
      studies at the Institute of Physiology of the Friedrich Wilhelms University
      between 1896 and 1900. After this, he turned to cardiology. Besides articles on
      urology, he published papers on psychiatry and cardiology. He was an active
      member of medical societies in Berlin and was awarded the title of a professor.
      Eugen Rehfisch died on October 7, 1937 in Berlin. His grave is in the cemetery of
      the Jewish congregation in Berlin Weissensee. The Eugen Rehfisch innovation prize
      is an expression of our admiration.

PMID- 15719245
TI  - Palmar atypical lipomatous tumour with spindle cell features (well-differentiated
      spindle cell liposarcoma): a rare neoplasm arising in an unusual anatomical
      location.
AB  - Lipomatous tumours, both benign and malignant, arising on the hands are uncommon.
      We present a rare atypical lipomatous tumour with spindle cell features (synonym:
      well-differentiated spindle cell liposarcoma) arising on the left palm of a 54
      year-old male patient. The neoplasm presented as a long-standing, exophytic
      neoplasm measuring 9 x 9 cm. The well-circumscribed neoplasm was completely
      excised, and margins were tumour free. Histologically, the neoplasm showed
      features closely resembling spindle cell lipoma, being composed of mature
      adipocytic cells associated with bland, neuroid spindle cells staining positively
      for CD34. However, focally, atypia of adipocytic and stromal cells as well as
      scattered lipoblasts were noted, and immunohistochemical stainings showed focal
      overexpression of MDM 2 and CDK4. Aypical lipomatous tumour with spindle cell
      features may arise very rarely in palmar location and has to be distinguished
      from a number of benign and malignant mesenchymal neoplasms.

PMID- 15719246
TI  - Does predation contribute to tree diversity?
AB  - Seed and seedling predation may differentially affect competitively superior tree
      species to increase the relative recruitment success of poor competitors and
      contribute to the coexistence of tree species. We examined the effect of seed and
      seedling predation on the seedling recruitment of three tree species, Acer rubrum
      (red maple), Liriodendron tulipifera (yellow poplar), and Quercus rubra (northern
      red oak), over three years by manipulating seed and seedling exposure to
      predators under contrasting microsite conditions of shrub cover, leaf litter, and
      overstory canopy. Species rankings of seedling emergence were constant across
      microsites, regardless of exposure to seed predators, but varied across years. A.
      rubrum had the highest emergence probabilities across microsites in 1997, but Q.
      rubra had the highest emergence probabilities in 1999. Predators decreased
      seedling survival uniformly across species, but did not affect relative growth
      rates (RGRs). Q. rubra had the highest seedling survivorship across microsites,
      while L. tulipifera had the highest RGRs. Our results suggest that annual
      variability in recruitment success contributes more to seedling diversity than
      differential predation across microsites. We synthesized our results from
      separate seedling emergence and survival experiments to project seedling bank
      composition. With equal fecundity assumed across species, Q. rubra dominated the
      seedling bank, capturing 90% of the regeneration sites on average, followed by A.
      rubrum (8% of sites) and L. tulipifera (2% of sites). When seed abundance was
      weighted by species-specific fecundity, seedling bank composition was more
      diverse; L. tulipifera captured 62% of the regeneration sites, followed by A.
      rubrum (21% of sites) and Q. rubra (17% of sites). Tradeoffs between seedling
      performance and fecundity may promote the diversity of seedling regeneration by
      increasing the probability of inferior competitors capturing regeneration sites.

PMID- 15719247
TI  - Immunocytochemical localization of choline acetyltransferase and muscarinic ACh
      receptors in the antenna during development of the sphinx moth Manduca sexta.
AB  - Immunocytochemistry with monoclonal antibodies was used to investigate the
      locations of muscarinic acetylcholine receptors (mAChR) and choline
      acetyltransferase (ChAT) in sections of the developing antennae of the moth
      Manduca sexta. The results were correlated with a previous morphological
      investigation in the developing antennae which allowed us to locate different
      cell types at various stages of development. Our findings indicated that the
      muscarinic cholinergic system was not restricted to the sensory neurons but was
      also present in glial and epidermal cells. By day 4-5 of adult development,
      immunoreactivity against both antibodies was present in the axons of the antennal
      nerve, and more intense labeling was present in sections from older pupae. At
      days 4-9, the cell bodies of the sensory neurons in the basal part of the
      epidermis were also intensely immunolabeled by the anti-mAChR antibody. In mature
      flagella, large numbers of cells, some with processes into hairs, were strongly
      labeled by both antibodies. Antennal glial cells were intensely immunolabeled
      with both antibodies by days 4-5, but in later stages, it was not possible to
      discriminate between glial and neural staining. At days 4-9, we observed a
      distinctly labeled layer of epidermal cells close to the developing cuticle. The
      expression of both ChAT and mAChRs by neurons in moth antennae may allow the
      regulation of excitability by endogenous ACh. Cholinergic communication between
      neurons and glia may be part of the system that guides axon elongation during
      development. The cholinergic system in the apical part of the developing
      epidermis could be involved in cuticle formation.

PMID- 15719248
TI  - [Minimally invasive otoplasty].
AB  - OBJECTIVE: We have further developed a method, first published in 1967 by Kaye
      but not widely used later, to correct protruding ears. To our knowledge, clinical
      experience with a closed otoplasty technique based on a large number of patients
      has not yet been published. SUBJECTS AND METHODS: Of 442 ears in 4.5 years, 385
      (200 patients, 15 one sided) were corrected using the minimally invasive
      technique. The key part of this technique to such otoplasty is the creation of a
      naturally appearing antihelix by combining permanent buried sutures and a
      conservative cartilage-breaking technique, both applied without extensive skin
      incisions and excisions. RESULTS: A total of 154 of the patients (i.e., with six
      one sided corrections, 302 ears) could be examined at least 3 months after
      surgery. Complications were revisions for either a partial recurrence or a still
      insufficient correction in the opinion of the patient (30/302, 9.9%), reactions
      to the suture material (26/302, 9.3%), early infections (2/385, 0.7%), prolonged
      sensitivity (2/302, 0.7%) and one hypertrophic scar in the lobule (1/302, 0.3%).
      There was no bleeding, hematoma, hypesthesia, sensitivity to temperature or skin
      reactions in the auricle. CONCLUSIONS: Minimally invasive otoplasty is a surgical
      technique that allows the correction of most protruding ears. Very strong
      cartilage or a very high lateral conchal wall set the limits to such an approach.
      We found the cosmetic results and complication rates to match those of open
      methods. Since patient comfort seems to be higher, the method is better accepted.

PMID- 15719250
TI  - Has the time come for a successor to DMSA scintigraphy?

PMID- 15719251
TI  - Icodextrin re-absorption varies with age in children on automated peritoneal
      dialysis.
AB  - Information on the use of Icodextrin in children remains scarce; however, it is
      believed that the characteristics are similar across all ages. We report the use
      of Icodextrin in a cohort of pediatric automated peritoneal dialysis (APD)
      patients younger than those previously reported (n=8, median age of 2.8, range
      0.02-17.1 years). Net Icodextrin daytime dwell ultrafiltration was calculated in
      each patient for every day on therapy as ml/h/m2. Half of the patients showed re
      absorption even when reducing Icodextrin dwells from a median of 10 to 6 h. All
      four patients who re-absorbed the Icodextrin (ranging from -23.7+/-7.5 to -2.5+/
      6.0 ml/h/m2) were treated with cyclic nocturnal APD, and three of these four
      patients were high transporters on the peritoneal equilibration test (PET).
      Icodextrin fluid removal correlated significantly with age (Spearman rank
      r=0.8571, P=0.0107). The data suggest that Icodextrin behaves differently in
      young children.

PMID- 15719252
TI  - Circannual variation in the onset and relapse of steroid-sensitive nephrotic
      syndrome.
AB  - Idiopathic nephrotic syndrome is the most common form of nephrotic syndrome in
      children, but little is known about the etiology of the disease. To obtain new
      insights into the etiology of the disease, we studied circannual patterns of
      initial episodes and relapses of steroid-sensitive nephrotic syndrome (SSNS).
      From 1986 to 2003, there were 45 children with SSNS in our hospital, and they
      experienced 43 relapses during that period. Initial episodes of SSNS were found
      to show significant circannual variation with an autumn peak both by Roger's test
      and Freedman's test, and the circannual pattern was more obvious in patients with
      high serum IgE levels. Chronological evaluation by means of Fourier analysis
      showed a clear circannual pattern. In contrast, relapses of SSNS showed
      circannual variation with a spring peak, which was a result of a high frequency
      of relapses after upper respiratory infections in January. These results suggest
      that circannual variation in initial episodes of SSNS might be associated with
      allergic predisposition, whereas circannual variation in relapses might be
      associated with preceding upper respiratory infections.

PMID- 15719253
TI  - Switch from cyclosporine A to mycophenolate mofetil in nephrotic children.
AB  - Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment
      in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic
      syndrome (NS). We analyzed nine children (age: 3.3-15.7 years, two girls) with SD
      or SR NS who experienced a significant decrease in their GFR under CyA treatment
      as measured by inulin clearance (C(IN)). Mycophenolate mofetil (MMF) was
      introduced progressively until doses of 1 g/1.73 m(2) twice daily were reached.
      CyA treatment was stopped after introduction of MMF and oral steroids were
      reduced if possible. After a median follow up of 261 days, no adverse effects of
      MMF such as diarrhea or hematological anomalies occurred in our patients. After
      switching from CyA to MMF, those children with SD NS remained in remission
      without proteinuria and those with SR NS did not show any significant changes in
      their residual proteinuria. The serum protein level did not change significantly
      in any of the children analyzed. GFR increased from a mean of 76.9+/-4.8 to
      119.9+/-5.9 mL/1.73 m(2) per min (P<0.001). Oral steroid treatment could be
      reduced from a median [range] prednisone dose of 0.85 [0.26-2.94] mg/kg/d pre-MMF
      to 0.29 [0-1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately
      after CyA withdrawal, but the difference did not reach statistical significance.
      We conclude that a switch from CyA to MMF seems to be safe for children with SDNS
      and SRNS in terms of side effects as well as disease control, at least in the
      short term. Interruption of CyA treatment lead to rapid amelioration of kidney
      function in these children, often associated with steroid sparing, which may lead
      to additional benefit for growth velocity, blood pressure and physical
      appearance.

PMID- 15719254
TI  - Retinoic acid may increase the risk of bone marrow transplant nephropathy.
AB  - Bone marrow transplant nephropathy (BMTN) classically presents more than 100 days
      after transplantation as an acute nephritis with hypertension, azotaemia and
      anemia that usually results in end stage renal failure (ESRF). The risk of
      developing BMTN may be greater with the use of more intensive chemotherapy and
      higher total body and tumor bed irradiation. Cis-retinoic acid (RA) may further
      increase the risk of developing BMTN. Here, we report the cases of two children
      who developed typical clinical and biochemical features of BMTN. They were both
      treated for stage IV neuroblastoma with chemotherapy, bone marrow transplant
      (BMT) conditioning that included total body irradiation and RA therapy after BMT,
      although the patient in case 1 had established renal insufficiency prior to the
      commencement of RA. Renal biopsy of these children showed classical BMTN
      histology, and the renal manifestations progressed quickly; the patient in case 1
      became dialysis dependent by 1 year post-bone marrow transplant. Recently, RA has
      been added to the post-BMT therapy in children with stage IV neuroblastoma. The
      occurrence of BMTN in two children treated with RA in our unit is unlikely to be
      coincidental. Although RA has been shown to confer a significant survival
      advantage in this disease, animal studies and a previous case report have
      suggested it could increase the toxic effects of chemotherapy and renal
      irradiation. It is likely that RA contributed to the deterioration in renal
      function in these patients.

PMID- 15719255
TI  - Phenotype and genotype of Dent's disease in three Korean boys.
AB  - Dent's disease is a hereditary renal tubular disorder caused by mutations of the
      CLCN5 gene and is clinically characterized by low molecular weight proteinuria,
      hypercalciuria and nephrocalcinosis. This disease has been reported in several
      countries. However, there are some phenotypic differences between countries, such
      as hypophosphatemic rickets, progressive renal failure and hematuria. In this
      study, phenotypes were analyzed in three Korean boys with Dent's disease, and
      genetic diagnoses were performed using a new convenient method using peripheral
      blood RNA. Gene studies revealed two nonsense mutations, R637X in two patients
      and E609X in one patient. The phenotypes of the two patients with R637X were very
      similar to those of Japanese patients, i.e., they presented with asymptomatic
      proteinuria without rickets, renal failure or hematuria. The E609X patient was
      diagnosed genetically at 3 months of age before the onset of clinical symptoms
      because of superimposed furosemide-induced nephrolithiasis. This is the first
      report to characterize mutations in the CLCN5 gene in Korean patients with Dent's
      disease, and expands the spectrum of CLCN5 mutations by reporting a novel
      mutation, E609X. In addition, the mutational analysis using peripheral blood RNA
      can be easily applied in the clinical diagnosis.

PMID- 15719256
TI  - Mitral annular calcification and brown tumor of the rib in a child with chronic
      renal failure.
AB  - Mitral annular calcification and liquefaction necrosis of this lesion mimicking
      intracardiac tumor because of secondary hyperparathyroidism have been described
      in adult patients with chronic renal failure, but have not been reported in
      children. Chronic renal failure is one of the predisposing factors of this
      condition. We report the case of a 13-year-old patient with continuous ambulatory
      peritoneal dialysis with severe hyperparathyroidism who was found to have
      intracardiac and rib lesions considered to be brown tumors.

PMID- 15719258
TI  - Functional adrenergic receptor polymorphisms and idiopathic orthostatic
      intolerance.
AB  - OBJECTIVES: Idiopathic orthostatic intolerance (IOI) is a common disorder that is
      characterized by chronic orthostatic symptoms and substantial increases in heart
      rate and plasma norepinephrine concentrations that are disproportionately high
      while standing. Several features of the syndrome, including the tachycardia,
      tremulousness, and exaggerated norepinephrine have been considered potentially
      due to hypoactive or hyperactive states of adrenergic receptors of the
      sympathetic nervous system. The aim of this study was therefore to ascertain
      whether genotypes at eight polymorphic loci within five relevant adrenergic
      receptor genes (alpha2A, alpha2B, alpha2C, beta1 and beta2) influence the risk
      for IOI. METHODS: We studied 80 young men in military service (20 patients with
      IOI and 60 age-matched controls). All participants underwent a tilt table test
      including monitoring of blood pressure, heart rate and plasma catecholamines, in
      the supine position and during 30 min of standing. Genotyping at the eight loci
      (alpha2ALys251, alpha2BDel301-303, alpha2CDel322-325, beta1Gly49, beta1Arg389,
      beta2Arg16, beta2Glu27, beta2Ile164) was performed in all participants. Chi
      square tests of independence were used to test for associations between IOI and
      genotype. In addition, an association of the polymorphisms with haemodynamic
      variables (heart rate, supine and upright blood pressure) was ascertained using
      one-way variance analysis. RESULTS: For the beta1Gly49 polymorphism we found a
      decrease in the risk of IOI among persons who were homozygous (odds ratio, 0.88;
      95% confidence interval, 0.81-0.97). In addition, we found an association between
      beta1Gly49 and decreased heart rate in the upright position, regardless of IOI
      diagnosis. There were no associations with the other studied polymorphisms and
      IOI. CONCLUSIONS: Our current results suggest that the beta1Gly49 polymorphism is
      protective for IOI. This is likely one of several common genetic loci that may
      represent modifiers of IOI phenotypes.

PMID- 15719257
TI  - A mechanistic approach to inherited polycystic kidney disease.
AB  - There are approximately six and a half million people, of the estimated world
      population of six billion, with inherited polycystic kidney disease. Polycystic
      kidney diseases have a broad spectrum of associated findings that distinguish and
      define them as specific disease states. The dysregulation of renal tubular
      epithelial cell biology, including cell polarity, cell signaling, proliferation
      and apoptosis, basement membrane and matrix abnormalities, and fluid transport,
      has been postulated to contribute to cystogenesis. Evidence is currently
      accumulating that supports an association of the primary cilium and basal body,
      as well as the focal adhesion assembly, with polycystic kidney diseases. Renal
      cystogenesis may be the result of a disruption of a critical feedback loop that
      regulates tissue morphology based on the epithelial cell environment.

PMID- 15719260
TI  - Historic importance of some aspects of research by O. Wilford Olsen on hookworms
      (Uncinaria lucasi) in northern fur seals (Callorhinus ursinus) and Steller sea
      lions (Eumatopias jubatus) in 1951 on St. Paul Island, Alaska.
AB  - The purpose of this paper is to disseminate, more widely, certain historically
      important aspects of research by O. Wilford Olsen on hookworms (Uncinaria lucasi)
      in northern fur seals (Callorhinus ursinus) and Steller sea lions (Eumatopias
      jubatus) in 1951 on St. Paul Island, Alaska. Highly meaningful facets of the
      research were recorded only in a report with limited availability by Olsen in
      1952. Portions of his research presented here include measurements of hookworm
      free-living infective third-stage larvae (L3) and adults, photographs of bursae,
      and the conclusion that the species of hookworms (U. lucasi) is probably the same
      in both pinniped hosts. This information is especially important because very
      little has been published on taxonomy of hookworms in E. jubatus.

PMID- 15719259
TI  - Intestinal parasites may not cause nosocomial infections in psychiatric
      hospitals.
AB  - This study was conducted to determine whether nosocomial infections of intestinal
      parasites occur in psychiatric hospitals. Three fecal specimens were collected
      from each institutionalized patient in seven psychiatric hospitals of north
      Taiwan. Saline wet mounts were prepared to examine trophozoites, and the other
      parasite stages were detected using the formalin-ethyl acetate sedimentation
      technique. Hospital faculties were asked to complete a questionnaire on the
      demographic data, health status degree of disability, and recent occurrence of
      gastrointestinal distress of these patients. Of the 464 patients examined, 8.4%
      were found to be infected with one or more intestinal parasite species: 6.3%
      single infections, 1.5% double infections, and 0.6% triple infections.
      Significantly higher prevalences were found among the males, unmarried patients,
      those with lower education, institutionalized for more than 3 years, sent by
      social workers to the hospitals, with non-schizophrenic diseases, and with a
      higher degree of disability. However, only education, marriage, mode of
      hospitalization, and type of psychiatric disease were found to be significant
      determinants in a logistic regression model. The variation in prevalence related
      to demographic factors implies that nosocomial infections may not occur. The mode
      of hospitalization indicates that the patients may acquire the infections before
      hospitalization.

PMID- 15719261
TI  - Photomicrographic images of some features of Uncinaria spp (Nematoda:
      Ancylostomatidae) from otariid pinnipeds.
AB  - Photomicrographs of several morphologic features of hookworms (Uncinaria spp)
      from northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus
      californianus) pups are presented. The main purpose is to show and describe some
      physical characteristics of hookworms from the two hosts; it is not to decide
      from these attributes whether the Uncinaria spp are the same species. The number
      of species of Uncinaria in pinnipeds is uncertain and specimens need to be
      examined from the various infected seals and sea lions before the taxonomy of
      these parasites can be clarified. Information in the present paper should aid in
      this determination.

PMID- 15719262
TI  - Modified cellular immune responses in dogs infected with Echinococcus
      multilocularis.
AB  - Parasite-specific antigen responses and lymphocyte blastogenesis in dogs orally
      inoculated with Echinococcus multilocuralis metacestodes were examined. Serum
      IgG1 (Th2-oriented) and IgG2 (Th 1-oriented) levels against somatic and excretory
      secretory (ES) antigens of protoscoleces and adult worms increased from 7 days
      post-infection (DPI), with the highest responses against protoscolex excretory
      secretory antigen (PES). Specific blastogenesis of peripheral blood mononuclear
      cells (PBMC) against the parasite antigens was not observed during the 21-day
      infection period, but Peyer's patches cells from one out of two dogs at 21 DPI
      showed blastogenesis against PES (stimulation index: 4.65). Interestingly, only
      at 7 DPI were concanavalin A (ConA)-induce proliferative responses of PBMC
      reduced. Moreover, ConA-induced proliferative responses of lymphocytes from
      various origins were suppressed by the addition of parasite antigens, especially
      with PES. These data suggest that although both Th1- and Th2-oriented humoral
      immune responses were observed in E. multilocularis infected dogs, the parasite
      antigens, especially PES, may have incompletely suppressed lymphocyte responses
      in these dogs.

PMID- 15719263
TI  - Fasciola hepatica: an unusual case of adaptation to a Moroccan population of
      Galba truncatula.
AB  - Parent snails, F1, and F2, originating from a Moroccan population of Galba
      truncatula, were experimentally subjected to sympatric miracidia of Fasciola
      hepatica at 20 degrees C to determine the mode of adaptation of this parasite to
      the local intermediate host via the study of redial burdens and by following
      cercarial shedding. In spite of an increase in the global prevalences of
      infections, the frequencies recorded for immature or mature infections in
      dissected snails did not show any significant variations from parents to F2. If
      the redial burdens in mature infections were mainly composed of first-generation
      rediae in parent snails, the numbers of rediae belonging to subsequent
      generations significantly increased in the F1 and F2 generations. In mature
      infections, the lengths of first-generation rediae and their contents
      significantly decreased from parent snails to F2. Conversely, in the first redial
      cohort of the second generation (R2a rediae), only the intraredial contents
      increased significantly with snail generation. In mature infections, daughter
      redia production was ensured by all mother rediae of the first generation in
      parent snails, whereas it was progressively effected by the first mother redia in
      the F1 and F2 infections. The numbers of cercariae shed by snails increased
      significantly from parents to F2. If the cercariae produced by first-generation
      rediae decreased with snail generation, an inverse finding was noted in the case
      of R2a rediae. We suggest that snails impose a bottleneck on the development of
      the first mother redia, so that other mother rediae of the first generation react
      with greater growth (until 3.9 mm in parent snails), an important daughter redia
      production and a high cercarial production. As the first mother redia remained
      alive until day 49 post-exposure but without growth after week 2, this mode of
      development must be considered as a new developmental pattern of redial
      generations, and it is useful to determine its frequency in snails, as it has
      never been found in naturally or experimentally infected snails in central
      France.

PMID- 15719265
TI  - The addition of fenugreek extract (Trigonella foenum-graecum) to glucose feeding
      increases muscle glycogen resynthesis after exercise.
AB  - The purpose of this study was to determine the effects of ingesting an oral
      supplement containing 4-Hydroxyisoleucine (4-OH-Ile, isolated from fenugreek
      seeds [Trigonella foenum-graecum]) with a glucose beverage on rates of post
      exercise muscle glycogen resynthesis in trained male cyclists. Following an
      overnight fast (12 hr), subjects completed a 90-minute glycogen depletion ride
      after which a muscle biopsy was obtained from the vastus lateralis. Immediately
      and 2 hours after the muscle biopsy, subjects ingested either an oral dose of
      dextrose (Glu) (1.8 g.kg BW(-1)) or 4-OH-Ile supplement (Glu+4-OH-Ile, including
      2.0 mg.kg(-1) 4-OH-Ile with the same oral dose of dextrose) with a second muscle
      biopsy 4 hours after exercise. Post exercise muscle glycogen concentration was
      similar for both trials. Overall, there was a significant increase in glucose and
      insulin concentrations from time 0 throughout the majority of the 4-hour recovery
      period, with no significant differences between the two trials at any time point.
      Although muscle glycogen concentration significantly increased from immediately
      post exercise to 4 hr of recovery for both trials, the net rate of muscle
      glycogen resynthesis was 63% greater during Glu+4-OH-Ile (10.6+/-3.3 vs. 6.5+/
      2.6 g.kg wet wt.(-1).hr.(-1) for the Glu+4-OH-Ile and Glu trials, respectively).
      These data demonstrate that when the fenugreek extract supplement (4-OH-Ile) is
      added to a high oral dose of dextrose, rates of post-exercise glycogen
      resynthesis are enhanced above dextrose alone.

PMID- 15719264
TI  - [Treatment results after surgery for basal cell carcinomas of the head and neck
      region taking into consideration various reconstruction techniques].
AB  - BACKGROUND: Basal cell carcinomas are the most frequently occurring malignant
      tumors in the white population. They exhibit a multitude of
      histological/morphological forms. PATIENTS AND METHOD: All cases of basal cell
      carcinoma treated at the department for oral and maxillofacial and regional
      plastic surgery of the HELIOS hospital in Erfurt between 1976 and 2003 were
      analyzed and partly reexamined in a retrospective study. RESULTS: A total of 648
      patients with 765 basal cell carcinomas were treated. Occurrences in females
      dominated those in males with a frequency distribution of 1.24:1. The average age
      was 70.6 years with a significantly larger number of female seniors above 60. In
      64% of the cases the basal cell carcinomas were nodular, in 16% infiltrative.
      Other morphological/histological forms occurred with a frequency of <or=5%. The
      most frequent localizations were in of the regions of the highest sun exposure
      such as the nose, midface, and forehead. DISCUSSION: If an infiltrative basal
      cell carcinoma is suspected or insufficient radical primary surgery is presumed,
      plastic reconstruction should be postponed until free margins can be confirmed
      histologically. The functional and aesthetic quality of reconstruction was better
      using pedicled flaps (90%) and primary closure (86%) than using free skin
      transplants (30-54%). Nevertheless, free skin flaps and epitheses were found to
      be well accepted by the reexamined patients.

PMID- 15719266
TI  - Neuro-oncology in a nutshell.

PMID- 15719267
TI  - Expression of cathepsin B and microvascular density increases with higher grade
      of astrocytomas.
AB  - Samples were taken from supratentorial gliomas border and normal brain autopsy
      which were divided into four groups, these including eight cases normal brain
      tissues, 30 cases of astrocytomas, 25 cases of anaplastic astrocytomas and 22
      cases of glioblastomas. Cathepin B (CB) expression and microvessel density (MVD)
      were determined with immunohistochemical studies. Staining results of CB was
      scored according to the percentage of positive cells, graded as negative (-),
      weak (+), moderate (++), and strong (+ + +). MVD was analyzed by Weidner's
      revised technique. CB positive staining was negative in eight cases of normal
      brain tissue. Only 9 out of 30 cases of astrocytomas showed a low percentage of
      positive cells that were stained in a light, diffuse cytoplasmic pattern (score
      +). Twenty-two out of 35 cases of anaplastic astrocytomas showed positive light,
      granular staining pattern, it including five samples (score +), and 17 samples
      (score + +). In contrast, all 22 cases of glioblastomas were stained all, and it
      was present in a course, granular staining pattern with an intensity of score (+
      +) of two sample, and score (+ + +) of 20 samples. Positive staining tumor cells
      were found in extracellular matrix (ECM), basement membrane (BM), and the
      endothelial cells of blood vessels were also positive stained. Along with
      elevating glioma grade, CB expression and MVD value were both increased.
      Therefore, it showed MVD value was positive correlated with expression of CB. It
      highly suggested that CB and angiogenesis plays an important role in glioma
      progression.

PMID- 15719269
TI  - In vitro effects of topotecan and ionizing radiation on TRAIL/Apo2L-mediated
      apoptosis in malignant glioma.
AB  - The survival of patients with malignant gliomas is still unsatisfactory despite
      multimodality treatment, therefore new therapeutic strategies are required. Tumor
      necrosis factor apoptosis related ligand (TRAIL/Apo2L), a member of the tumor
      necrosis factor superfamily, may induce apoptotic cell death in several tumors,
      but not in normal cells, upon binding with specific receptors. In the present
      study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL
      R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373,
      A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors.
      Our data show that gliomas preferentially express TRAIL R2 and that treatment
      with topotecan, a topoisomerase I inhibitor, significantly up-regulates its
      expression as detected by flow cytometry and western blotting. Moreover, in most
      cases, treatment with topotecan resulted in an increased sensitivity to TRAIL
      dependent apoptosis, although cyclohexymide had to be added to induce apoptosis.
      On glioma cell lines, the effects of irradiation on TRAIL receptors were also
      analysed. In our experimental conditions, irradiation with 2 Gy had a modest
      additive effect on TRAIL-dependent apoptosis and was not able to modulate TRAIL
      receptor expression.

PMID- 15719268
TI  - Effects of toxic doses of glutamate on Cu-Zn and Mn/superoxide dismutases
      activities in human glioma cell lines.
AB  - Recent research has implicated glutamate in the growth and invasive migration of
      gliomas. Superoxide dismutase (SOD) is involved in excitotoxicity and may
      influence cellular proliferative status. Thus, this study investigated the
      effects of gliotoxic doses of glutamate on Cu-Zn and Mn/SODs activities in human
      glioma cell lines. To this end, glioma cell lines (U87MG, U138MG and U251MG) were
      treated with glutamate (5-200 mM) during 48 h. Then, cell viability assays,
      clonogenic assay and Cu-Zn and Mn/SODs activities of the cell lines were
      performed. IC50values of glutamate were similar for both U87MG and U138MG cells
      (56 and 69 mM, respectively), while a higher value was detected for U251MG cells
      (110 mM). In the long term, 14 days after glutamate was removed from the culture
      media, cells showed partial or complete recovery. The effects of glutamate
      treatment on Cu-Zn and Mn/SODs activities varied among the distinct cell lines.
      While acute treatment with toxic doses of glutamate caused a significant decrease
      in the Cu-Zn/SOD activity of U138MG and U251MG cells, it did not affect Cu-Zn/SOD
      activity in U87MG cells. Only in U251MG cells, acute glutamate treatment
      decreased significantly Mn/SOD activity. In the long term (14 days after the 48 h
      treatment), glutamate did not affect either Cu-Zn or Mn/SODs activities. Thus, it
      may be suggested that SOD vulnerability to glutamate-mediated effects may be
      related to distinct tumoral cell behavior.

PMID- 15719271
TI  - Central neurocytoma.

PMID- 15719270
TI  - Atypical molecular background of glioblastoma and meningioma developed in a
      patient with Li-Fraumeni syndrome.
AB  - We observed three neoplasms with completely different histologies: malignant
      fibrous histiocytoma (MFH), atypical meningioma (AM), and glioblastoma (GB),
      developing in a patient with Li-Fraumeni syndrome. By using a combined molecular
      approach we performed molecular characterization of all three tumours. Data
      obtained showed an interesting molecular background of the AM and GB. AM showed
      TP53mutations and a 22q loss of heterozygosity (LOH). GB showed epidermal growth
      factor receptor (EGFR) amplification and TP53 mutations, whereas P16, PTEN,
      Rbwere intact in terms of LOH and/or multiplex PCR (polymerase chain reaction)
      analysis. Additionally, GB has a 1q LOH, which is an extremely rare alteration in
      glioblastomas. Identical 1q LOH was also observed in MFH.

PMID- 15719272
TI  - High-dose chemotherapy with autologous stem cell rescue for children with high
      risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal
      tumors.
AB  - Current treatment for high risk and recurrent medulloblastoma (MB) and
      supratentorial primitive neuroectodermal tumors (stPNET) has a very poor
      prognosis in children. High dose chemotherapy (HDCT) and autologous stem cell
      rescue have improved survival rates. We present 19 patients (thirteen classified
      in the high risk group and six patients with recurrent disease) that received
      HDCT and autologous stem cell rescue. In the high risk group [Med Pediatr Oncol
      38 (2002) 83], all patients underwent neurosurgical debulking. Standard
      chemotherapy was prescribed in 10 patients. Radiotherapy was given to 4 patients
      (all older than 4 years old). In the recurrence disease group [Childs Nerv Syst
      15 (1999) 498], five patients underwent surgery. Radiotherapy was given to those
      who were not previously irradiated. The HDCT in twelve patients consisted of
      busulfan 4 mg/kg/day, orally over 4 days in 6-hourly divided doses and melphalan
      at a dose of 140 mg/m2/day by intravenous infusion over 5 min on day -1. Three
      patients additionally received thiotepa 250 mg/m2/day intravenously over 2 days
      and four patients additionally received topotecan 2 mg/m2/day over 5 days by
      intravenous infusion over 30 min. The other seven patients received busulfan and
      thiotepa at the same doses.Patient's stem cells were mobilized with granulocyte
      colony-stimulating factor at a dose of 12 microg/kg twice daily subcutaneously
      for four consecutive days. Cryopreserved peripheral blood progenitor cells were
      re-infused 48 h after completion of chemotherapy. With a median follow-up of 34
      months (range 5-93) eight complete responses and one partial response were
      observed. Three patients died of treatment-related toxicities (15%). The 2 year
      event-free survival was 37.67+/-14% in all patients and 57+/-15% for the high
      risk group. Therefore we conclude that HDCT may improve survival rates in
      patients with high risk/recurrent MB and stPNET despite treatment toxicity.

PMID- 15719273
TI  - Clinical relevance of non-neuronal auto-antibodies in patients with anti-Hu or
      anti-Yo paraneoplastic diseases.
AB  - About half of the patients with paraneoplastic diseases develop an immune
      response against neuronal antigens expressed by both the tumor and the nervous
      system. In 31 patients with anti-Hu antibodies and 19 patients with anti-Yo
      antibodies, we searched for the presence of additional non-neuronal auto
      antibodies and further studied whether the presence of such auto-antibodies was
      correlated with a specific oncological or neurological presentation. Positive
      antinuclear antibodies (ANA) were found at a titer of 1:40 or above in 48%
      patients with anti-Hu antibodies, and in 37% patients with anti-Yo antibodies.
      Anti-cytoplasmic antibodies were also detected in 42% patients with anti-Yo
      antibodies. No specific correlation between the presence of non-neuronal auto
      antibodies and clinical characteristics of the patients could be identified. In
      particular, neither the type of underlying cancer, the overall survival, the
      tumor response to treatment, nor the neurological presentation were related to
      the serological status.

PMID- 15719274
TI  - Brain metastasis in pediatric extracranial solid tumors: survey and literature
      review.
AB  - OBJECTIVES: Brain is a rare site of metastasis in most extracranial pediatric
      solid tumors. The aim of this study is to investigate the incidence, treatment,
      prognosis of brain metastasis in extracranial pediatric malignant tumors in a
      single institution and to review the literature. METHODS: From September 1989 to
      December 2002, 1100 children <or=16 years of age with extracranial solid tumors
      including lymphomas were diagnosed and treated in the Division of Pediatric
      Oncology, Oncology Institute, Istanbul University. Patients with parenchymal
      metastases in the brain were assessed. RESULTS: Sixteen (10 female, 6 male) of
      1100 patients (1.45%) with extracranial solid tumors developed brain metastases.
      The median age of the patients was 10.5 (1-16) years. The diagnosis was sarcomas
      in 12 patients: 5 osteosarcomas, 4 Ewing's sarcoma family tumors, 1
      rhabdomyosarcoma, 1 clear cell sarcoma of the soft tissue, 1 alveolar soft part
      sarcoma. Two patients had Wilms' tumor and two had germ cell tumors. Four
      patients (25%) had brain metastasis at diagnosis. Twelve (75%) developed brain
      metastasis during therapy or relapse at a median duration of 16 (1-70) months
      from initial diagnosis. All patients had metastases to various sites, mostly
      lung, at the time the brain metastases were detected. Treatment included surgery,
      followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 1, S and RT
      in 1, S in 1, RT and CT in 6, RT in 1, CT in 1 and no treatment in 5. Only one
      patient with alveolar soft part sarcoma is alive with disease 20 months from
      diagnosis of brain metastasis. All other patients died at a median time of 2
      months (2 days-6 months) from the time of brain metastasis. CONCLUSIONS: Children
      with metastatic cancer who develop headaches or any other neurologic symptom
      should be investigated for possible brain metastasis. Although, the outcome for
      these patients is dismal in this series and in the literature; reports of long
      term survival in a few cases with Wilms' tumor, osteosarcoma and alveolar soft
      part sarcoma who had isolated brain metastasis, suggest that a subset of patients
      may benefit from therapy.

PMID- 15719275
TI  - Isolated primary intracerebral mycetoma: presenting as a mass lesion in a patient
      with prostate cancer and multiple myeloma.
AB  - We report a patient with a history of prostate cancer and multiple myeloma, with
      a solitary indolent intracerebral mass lesion without any constitutional symptoms
      and minimal neurologic symptoms. The radiographic appearance of the lesion was
      that of a tumor but resection revealed a mycetoma, consistent with Aspergillus. A
      brief review of the literature discusses the rarity, presentation, diagnosis, and
      management of primary intracerebral mycetomas.

PMID- 15719276
TI  - Cerebellar liponeurocytoma/lipidized medulloblastoma.
AB  - Cerebellar liponeurocytoma that has been recently identified as a distinct entity
      by the World Health Organization is characterized by areas of lipomatous
      differentiation and apparently by a favorable prognosis. In this paper, we
      described a case of 49-year-old female showing progressive clinical course
      inspite of a low labeling/mitotic index. We also review the relevant literature.
      Although, basically all reported cases share a similar histological pattern, i.e.
      focal accumulations of adiposities in an otherwise typical small cell tumor like
      central neurocytoma, some clinical properties such as (age, proliferative
      potential, therapy and survival) are not uniform. The exact biological behavior
      of this special variant tumor is established. Yet, this needs further
      confirmation on a large number of cases with longer follow-up periods.

PMID- 15719277
TI  - Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain
      metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase
      II study.
AB  - PURPOSE: To evaluate the efficacy of temozolomide (TMZ) combined with cisplatin
      (CDDP) in terms of response rate, time to progression (TTP) and overall survival
      (OS), as well as the tolerability of the regimen in patients with brain
      metastases from solid tumors. PATIENTS AND METHODS: Patients (n=32) with brain
      metastases were treated with TMZ 150 mg/m2/day (chemotherapy-pretreated) or 200
      mg/m2/day (chemotherapy-naive) for 5 days, combined with CDDP 75 mg/m2 on day 1,
      every 28 days. Primary tumor sites included breast cancer (n=15), lung cancer
      (n=12) and other (n=5). Twenty-seven patients had received prior chemotherapy for
      extracranial disease and 17 had prior radiotherapy to the brain. RESULTS: One
      patient (3.1%) with non-small cell lung cancer (NSCLC) achieved complete
      response. Nine patients (28.1%; six with breast cancer, two with melanoma and one
      with NSCLC) achieved a partial response and five patients (16%) had stable
      disease. Median OS was 5.5 months and median TTP 2.9 months. One patient died
      from septicemia/neutropenic fever. Grade III-IV toxicities included anemia (9%),
      leukopenia (6%), thrombocytopenia (3%), renal toxicity (3%), headache (3%),
      fatigue (3%), nausea (3%), vomiting (3%), and alopecia (6%). CONCLUSIONS: TMZ
      combined with CDDP is an active and well-tolerated combination in patients with
      brain metastases from solid tumors.

PMID- 15719278
TI  - Intramedullary spinal cord metastases in breast cancer: report of four cases and
      review of the literature.
AB  - Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly
      progressing systemic cancer. Breast cancer represents one of the most common
      solid tumors associated with the development of ISCM at rather advanced stages of
      disease. In the present report we describe four new cases with advanced breast
      cancer developing ISCM. All cases presented herein indicated that ISCM is a late
      manifestation of disseminated breast cancer. Three of these patients had been
      treated for approximately 1-3 years for metastatic disease. Once ISCM developed,
      concurrent asymptomatic brain metastases were detected in one case, concurrent
      symptomatic brain disease (cerebellar) was present at the time of cervical ISCM
      diagnosis in another patient, and in another case, ISCM developed metachronously
      at 18 months after the diagnosis of symptomatic brain metastases treated by whole
      brain radiotherapy. One of these cases had brain metastases at presentation,
      while at relapse developed leptomeningeal carcinomatosis treated successfully,
      but followed shortly, as a terminal event, by ISCM and parenchymal brain
      recurrence. All but one patient experienced a rather rapidly evolving disease
      course leading to death after 2-5 months from widespread neuraxis dissemination
      of their cancer, while one patient is still alive 6 months after the diagnosis of
      ISCM. All four cases, added to the list of the anecdotally reported cases of ISCM
      after breast cancer, undermine the ominous prognosis and limited treatment
      options available for this disease manifestation, and an extensive literature
      review and discussion of similar cases is provided.

PMID- 15719282
TI  - [Sources of law].
AB  - In it first article, the Civil Code establishes that the sources of Spanish law
      are law, custom, and the general principles of law as well as the circumstances
      in which each one of them is applied. The Spanish Constitution (SC) is the Law of
      Laws. It gathers the fundamental rights of the person who should respect the
      guidelines of the lower ranking. The Law is the guideline having the maximum
      category below the SC, its elaboration corresponds to the General Courts although
      the executive power may legislate in certain circumstances (by delegation of the
      legislative power or by emergency). Executive power elaborates Regulations that
      are technical developments of the laws. The regulations of the Regional
      Communities have the rank of law in their geographic setting and for the material
      in which it has competence. The validly agreed upon international treaties form a
      part of the Spanish set of rules after being published in the Official State
      Bulletin. The Spanish legal system is hierarchical, the rules coming from
      community law are within the peak of the pyramidal structure, with preference on
      the constitution, followed by laws and rules.

PMID- 15719283
TI  - [Legal framework of the medical profession and of the neurology speciality].
AB  - The law on the general organization of Health Care Professionals (GOHCP) and the
      Framework Statute make up a new regulatory framework for the practice of
      medicine, which is completed with the legal debate on the obligatory association
      to the medical college, pending in the Constitutional Court based on certain
      regional legal developments. The GOHCP defines the functions of the different
      professions according to degree, establishes a public registry of physicians,
      converts the obligation of practicing according to the state of the art into law
      and updates the training, introduces the Resident core training program and opens
      the door to superspecialities. It also regulates the professional career, in
      order to establish a common body of four grades to which the health services can
      add a fifth one with previous character. Among the novelties of the Framework
      Statute, there is extensive updating of the offences and sanctions -- that
      include aspects such as work harassment and adaptation of the workday to the
      European guidelines, so that the maximum workday is established in 48 hours per
      week and the complementary (having a voluntary character) cannot exceed 150 hours
      per year. Lowering retirement age to 65 years foreseen in this guideline will
      require planning of human resources and has already generated suits in the
      courts. The obligatory nature of belonging to the medical college has also been
      modified, this time by some guidelines on the regional level. They would require
      a decision by the Constitutional Court on whether the college members can be
      exempted in some cases.

PMID- 15719279
TI  - Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation
      sensitizer in patients with unresectable brain metastases.
AB  - PURPOSE: The primary goal of this phase I/II study was to evaluate the
      feasibility, safety and efficacy of celecoxib administered concomitant to
      radiotherapy to treat unresectable BM. PATIENTS AND METHODS: Patients with
      measurable BM by CT or MRI, unresectability criteria by a neurosurgeon and RPA
      RTOG class II were eligible. Celecoxib was administered at 400 mg/day during the
      entire course of radiotherapy. All patients were irradiated with 60Co beams to
      whole-brain dose of 32 Gy (20 fractions of 1.6 Gy each two times a day with a 6 h
      interval between treatments) followed by a 22.4 Gy boost (same fractionation
      schedule) over evident lesions. RESULTS: Twenty-seven patients were treated. The
      concurrent regimen was well tolerated with 15 cases of mild dyspepsia. Alopecia
      (NCI grades 1-2) was the most important side effect. Three patients presented
      rash/desquamation of moderate intensity. Radiological responses occurred in 18 of
      25 valuable patients (72), with five complete responses (CR). Symptomatic
      responses were reported in 25 of 27 patients (92.6), with 20 CR. The overall
      response rate (considering complete plus partial responses) was 66.7. Percentile
      50 for time-to-progression, time-to-neurological-progression and functional
      independence-time were 3, 6.25 and 6.7 months, respectively. Median survival time
      was 8.7 months. CONCLUSION: Our initial results suggest that radiotherapy plus
      celecoxib is safe and a possible active treatment for patients with BM. Further
      investigation in a randomized trial is warranted to validate its clinical
      utility.

PMID- 15719284
TI  - [Clinical history: its use and confidentiality].
AB  - Prior to the entry in forces of Law 41/2002, the clinical history was regulated
      by internal functioning guidelines of the Sites and by the Ethics and Medical
      Deontology Code. The new law establishes the concept, composition, content,
      conservation and custody of the clinical history. It also foresees the
      establishment of guidelines that facilitate the coordination between the
      different regional communities in order to homogenize this documentation and make
      it compatible. The law also regulates access, use, and control of the clinical
      history and the documentation contained in it as well as its limitations and role
      of the professionals in establishing them. On the other hand, it determines the
      obligation of confidentiality on the data contained in it and who it affects. The
      clinical history is an obligation and right of the professional since it not only
      facilitates the care but also is the most important probative element in cases of
      claims of responsibility, having a clarifying function.

PMID- 15719285
TI  - [Legal responsibility in the exercising of the neurology clinical practice].
AB  - The importance of responsibility in the clinical practice is derived from the
      transcendency of what they affect (life and health) and the risk implicit to it.
      The clinical performance does not require curing. The obligations that are
      derived from them are means and not results. It is also not correct to associate
      error and responsibility. Responsibility of the professional may be claimed by
      civil, patrimony, corporative, disciplinary and penal routes based on the reasons
      and according to who is making the claim. These claims may be presented
      individually or jointly based on whether the modality of the professional
      practice is free or carried out by others, whether in public health or private
      health care. The professional has different alternatives to respond to the
      possible lawsuits that are presented, both penal and civil action or protection
      have the common problem of the difficulty of proof.

PMID- 15719286
TI  - [Expertise test in the new Civil Prosecution Law (Law 1/2000)].
AB  - Expertise test was the object of many controversies in the previous Civil
      Prosecution Law (CPL) from the way of naming the experts to the difficulties in
      the receiving payment. The new CPL uses the social process as model and provides
      civil justice with an agile and guaranteeing procedure. The CPL provides the
      expert test with a greater amplitude and new range, and should be used at the
      time of the lawsuit and openly seen. The experts should assume the defense of
      their arguments and be subjected to the objections of the contrary party. The
      expert's test becomes a mixed documental and personal test. It also modifies the
      way of naming the experts and the acceptance that may condition the allocation of
      funds in the amount considered necessary. The objection is limited to the experts
      named judicially, it being possible to eliminate them, however, the reason for it
      should be justified.

PMID- 15719287
TI  - [Patient autonomy].
AB  - Respecting the patient's autonomy is one of the fundamental principles on which
      biomedical ethics is based. The principle of autonomy considers the patient's
      freedom and responsibility, who decides what is good for himself/herself,
      although this is not shared by the physician. In the field of medical research,
      there are codes and guidelines that guarantee the protection of persons as
      research subjects. In Spain, recognition of the right of the patient's autonomy
      has been included in different legal and deontological guidelines. Law of
      Patient's Autonomy 41/2002 (LAP) is a response to the growing important in our
      society of the patients' rights as basic axis of the clinical-health care
      relationships. Different regional communities have also enacted legal guidelines
      that regulate the persons' autonomy to decide about that affecting his/her
      health, physical integrity, or life as well as the assumption by others of the
      decisions of representation or previous instructions. The basic paradigm of
      autonomy is the informed consent. The LAP establishes the obligation of obtaining
      the free and voluntary consent of the patient prior to any type of intervention,
      after offering him/her the adequate information. This basic guideline specifies
      the situations in which the informed consent is given in writing as well as the
      exceptions to this consent. Finally, the LAP details when the informed consent is
      advisable by representation, closely linked to the patient's capacity as well as
      the regulation of previous instructions.

PMID- 15719288
TI  - [Jurisdiction and imputability].
AB  - Validity, efficacy and responsibility of acts depend on the intelligence and will
      of the acting subject; therefore when they are reduced or debilitated, these acts
      may be declared as non-valid and the author, not-responsible for the acts. Some
      neurological pathologies may generate physical and/or psychic permanent
      deficiencies, which prevent subjects from acting on their own. For these cases,
      the law establishes the incapacity state, in order to protect the disabled and
      complete the reduced ability, guaranteeing their rights and security. The
      disabled state will be determined by a legal sentence, which states the lack of
      ability to manage. In that sentence extension and limits of the disability will
      be determined; disability level will be proportional to the insight
      degree.Similarly, a subject suffering a pathological condition that invalidates
      his/her will and intelligence will be considered non-responsible and not
      imputable, since there is no culpability ability. The Penal Code establishes the
      criteria that will determine the possibility of imputability or its absence, as
      well as modifying circumstances.

PMID- 15719289
TI  - [The neurologist and patients driving motor vehicles].
AB  - Driving motor vehicles is a complex visuomotor task that challenges normal
      nervous system functioning. Indemnity of sensory organs and intact alertness are
      essential. In addition, safe driving is extremely sensitive to disturbances of
      attention as well as to some forms of cortical dysfunction. Epilepsy, cognitive
      impairment, Parkinson's disease, stroke and sleep disorders, among other
      conditions, may interfere with driving through different mechanisms. The
      individual rights to maintain important privileges such as having a driver's
      license may enter in conflict with a society demanding safer regulations. Current
      trends favor more liberal restrictions and may provide specific limits on an
      individual basis to patients with impairments caused by neurological diseases. So
      far, there is no information on the consequences in terms of rate of accidents
      following newly introduced changes in driver license regulations for neurological
      patients.

PMID- 15719290
TI  - [Advanced directives document and neurologist-patient relationship].
AB  - Perception of health and disease, pain and suffering, quality of life, personal
      relationships, privacy and intimacy, culture and social values, can now be stated
      in a written document, by way of a living will, giving legal legitimacy to each
      patient's way of being and understanding life, to be used when the subject cannot
      express it by him/herself. In this way, the patients will participate in the
      therapeutic process and will incorporate their desires and decisions through the
      Informed Consent and the Advanced Directives Document (ADD). Both documents
      translate and indicate how to treat and care for a patient who will progressively
      lose his/her cognitive faculties and others will decided for him/her, in the case
      of dementias. The basis of ADD is respect and promotion of the patient's
      autonomy, prolonging his/her right to decide in the stages in which he/she cannot
      do it. It consists in some instructions or orientations for the patient to be
      cared for in a certain way, according to his/her will. To this effect, a
      representative will be named who will act in the subject's name and who will help
      to interpret and make decisions when the patient cannot. Specifically, in
      Alzheimer's disease, ADD allows the patient to decide, in full lucidity, freedom
      and autonomy, how to live a progressive and irreversible disease. Explicit
      mention can be made to the will of making his/her disease known publically or
      not, the care of its aspect, privacy, type of care, whether institutionalized or
      home care, limitation of visits, treatment intensity and prolongation, palliative
      cares, donation of biological samples, participation in drug clinical trials.

PMID- 15719291
TI  - [Comprehensive cancer centers in Germany: role of radiology].

PMID- 15719292
TI  - Aortic stentgraft movement detection using digital roentgen stereophotogrammetric
      analysis on plane film radiographs -- initial results of a phantom study.
AB  - PURPOSE: To evaluate the feasibility of aortic stentgraft micromovement detection
      using digital roentgen stereophotogrammetric analysis on plane film radiographs.
      MATERIAL AND METHODS: An aortic stentgraft used for demonstration purposes was
      marked with 10 tantalum markers of 0.8 mm in diameter. The stentgraft was placed
      on a Plexiglas phantom with 5 tantalum markers of 1 mm in diameter simulating a
      fixed segment needed for mathematical analysis. In a subsequent step, the
      stentgraft was placed onto an orthopaedic spine model to simulate in vivo
      conditions.in a next step. Two radiographs taken simultaneously from different
      angles were used for simulating different stentgraft movement, e. g. translation,
      angulation, aortic pulsation and migration in the spine model. Movement of the
      stentgraft markers was analysed using a commercially available digital RSA setup
      (UmRSA(R) 4.1, RSA Biomedical, Umea, Sweden). RESULTS: Our study shows the
      feasibility of measuring aortic stentgraft movement and changes in stentgraft
      shape in the submillimeter range using digital roentgen stereophotogrammetric
      analysis. Translation along the 3 cardinal axes, change in stentgraft shape,
      simulation of aortic pulsation and simulation of in vivo conditions could be
      described precisely. CONCLUSION: Aortic stentgraft movement detection using
      digital roentgen stereophotogrammetric analysis on plane film radiographs is a
      very promising, precise method.

PMID- 15719293
TI  - [Current state of molecular imaging research].
AB  - The recent years have seen significant advances in both molecular biology,
      allowing the identification of genes and pathways related to disease, and imaging
      technologies that allow for improved spatial and temporal resolution, enhanced
      sensitivity, better depth penetration, improved image processing, and beneficial
      combinations of different imaging modalities. These advances have led to a
      paradigm shift in the scope of diagnostic imaging. The traditional role of
      radiological diagnostic imaging is to define gross anatomy and structure in order
      to detect pathological abnormalities. Available contrast agents are mostly non
      specific and can be used to image physiological processes such as changes in
      blood volume, flow, and perfusion but not to demonstrate pathological alterations
      at molecular levels. However, alterations at the anatomical-morphological level
      are relatively late manifestations of underlying molecular changes. Using
      molecular probes or markers that bind specifically to molecular targets allows
      for the non-invasive visualization and quantitation of biological processes such
      as gene expression, apoptosis, or angiogenesis at the molecular level within
      intact living organisms. This rapidly evolving, multidisciplinary approach,
      referred to as molecular imaging, promises to enable early diagnosis, can provide
      improved classification of stage and severity of disease, an objective assessment
      of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging
      is an important tool for the evaluation of physiological and pathophysiological
      processes, and for the development of new therapies. This article comprises a
      review of current technologies of molecular imaging, describes the development of
      contrast agents and various imaging modalities, new applications in specific
      disease models, and potential future developments.

PMID- 15719295
TI  - [Detection and characterization of left ventricular thrombi by MRI compared to
      transthoracic echocardiography].
AB  - PURPOSE: Transthoracic echocardiography is the routine diagnostic procedure in
      assessing patients with left ventricular thrombi, but is limited by the acoustic
      window and poor contrast between thrombus and adjacent myocardium. This study
      evaluates the role of cardiac MRI in the detection of left ventricular thrombi in
      patients with chronic myocardial infarction compared to standard transthoracic
      echocardiography. MATERIALS AND METHODS: In 82 patients (55 men and 27 women, age
      36 to 79 years, median 59 +/- 11 years) who suffered a myocardial infarction more
      than 6 months earlier, transthoracic echocardiography and MRI were performed. The
      MRI protocol included steady state cine imaging (true FISP: TR 3.0 ms, TE 1.5 ms,
      FA 65 degrees ) in standard long and short axis orientation and contrast-enhanced
      imaging using a 3D IR-FLASH sequence with long inversion time (TR 4 ms, TE 1.43
      ms, FA 10 degrees , TI 300 ms) early, and a 2D IR-FLASH sequence with optimized
      inversion time (TR 8 ms, TE 4.3 ms, FA 20 degrees , TI 180 - 280 ms) late after
      administration of gadolinium. RESULTS: Transthoracic echocardiography depicted 12
      thrombi. Contrast-enhanced MRI confirmed these 12 thrombi and detected 23
      additional thrombi. With the exception of 2 very small apical thrombi only
      visible on contrast-enhanced MR images, spherical thrombi were diagnosed by both
      techniques, whereas only contrast-enhanced MRI was able to visualize mural
      thrombi. Left ventricular thrombi were more frequently diagnosed in patients with
      moderate to severe impairment of the left ventricular systolic function, 32/42
      (76 %), or in patients with left ventricular aneurysms, 21/24 (84 %). CONCLUSION:
      Contrast-enhanced MRI is mostly superior to transthoracic echocardiography in
      diagnosing mural left ventricular thrombi in patients who had suffered a
      myocardial infarction. Intracavitary thrombi are more frequently found in
      patients with impaired regional and global left ventricular function.

PMID- 15719294
TI  - [Detection of airways stenoses: comparison of virtual and flexible bronchoscopy].
AB  - PURPOSE: To compare virtual with flexible bronchoscopy for the detection of
      bronchial stenoses. MATERIALS AND METHODS: In a retrospective study, we compared
      the results of 26 patients, who had clinical suspected pathologies of the
      tracheobronchial airways and underwent both flexible bronchoscopy and multislice
      CT with 3D surface rendering of the airways. Flexible bronchoscopy and virtual
      bronchoscopy were compared as to the rate of detecting bronchial stenoses. For
      statistical analysis, we divided the tracheobronchial tree in the following
      sections: trachea, 2 main bronchi, 6 lobar bronchi, 18 segmental bronchi and 36
      subsegmental bronchi, corresponding to 63 bronchial sections for each patient (on
      average) and a total of 1638 bronchial sections for all 26 patients. We graded
      the bronchial stenosis as less than 50 %, as 50 to 95 % and as complete
      obstruction. RESULTS: Virtual bronchoscopy detected 25 bronchial stenoses, while
      flexible bronchoscopy only revealed 17 stenoses. Stenoses with a diameter less
      than 50 % were found with virtual bronchoscopy 14 times and with flexible
      bronchoscopy 10 times. Stenoses with a diameter between 50 and 95 % were detected
      7 and 4 times, respectively, and complete obstructions 4 and 3 times,
      respectively. Tracheobronchial stenoses were well recognized with virtual
      bronchoscopy. Moreover, the virtual method enabled the visualization of high
      grade stenoses and post-stenotic areas that could not be passed by the fiberoptic
      bronchoscope. Virtual bronchoscopy detected stenoses at a higher rate but the
      difference was not statistically significant (stenoses < 50 %: p = 0.352, 50 - 95
      %: p = 0.339, complete obstruction: p = 0.696). CONCLUSION: Virtual bronchoscopy
      is a useful non-invasive method for the diagnostic evaluation of the
      tracheobronchial tree. In comparison with flexible bronchoscopy, virtual
      bronchoscopy is superior in revealing high-grade stenoses and visualizing post
      stenotic areas.

PMID- 15719296
TI  - [3D motion adapted gating: a new navigator technique to shorten the acquisition
      time for coronary MRA].
AB  - PURPOSE: A major problem of free breathing coronary MR angiography (MRA) with
      respiratory navigator gating is low navigator efficiency and prolonged scan time
      due to irregular breathing patterns. 3D motion adapted gating (MAG) is a new
      adaptive navigator technique, which adapts in real time to changes of the end
      expiratory position of diaphragm. This study evaluates the influence of 3D MAG on
      coronary MRA. METHODS AND MATERIALS: In 3D MAG, two additional gating windows are
      grouped around the conventional window. Additionally, each gating window is
      divided into three bands assigned to different portions of the k-space. The scan
      is terminated when three consecutive bands are filled and one complete image data
      set is collected. Free breathing navigator-gated coronary MRA was performed on 48
      patients with suspected coronary artery disease. In random order, each patient
      underwent an ECG-gated, a 3D segmented k-space gradient echo sequence using 3D
      MAG and a conventional navigator technique. The coronary MRA was evaluated and
      compared using the following parameters: 1. navigator efficiency and scan time;
      2. visualized coronary artery length; 3. qualitative assessment of image quality;
      and 4. detection of stenoses > 50 % in comparison with catheter angiography.
      RESULTS: Coronary MRA with 3D MAG had a significant increase in the average
      navigator efficiency (46 % +/- 12 % vs. 38 % +/- 12 %, p < 0.05), resulting in a
      significantly shorter scan time (mean: 18 % +/- 4 %, p < 0.05) for coronary MRA
      with 3D MAG compared to conventional navigator technique. Scans with and without
      3D MAG had no significant differences in the continuously visualized vessel
      lengths, in the assessed image quality and in the sensitivity and specificity (83
      % and 89 % vs. 83 % and 88 %, p > 0.05) of detecting coronary artery stenoses >
      50 %. CONCLUSION: The 3D MAG technique improves the navigator efficiency and
      significantly (p < 0.05) shortens the scan time of navigator gated coronary MRA
      while maintaining image quality and diagnostic accuracy in the detection of
      coronary artery stenoses.

PMID- 15719297
TI  - [Differential diagnosis of the signal-compromised lunate in MRI].
AB  - PURPOSE: To define both the underlying pathology and diagnostic criteria in
      lunates presenting with conspicuous signal pattern in MRI. MATERIALS AND METHODS:
      The retrospective evaluation of 2940 MRI examinations revealed 203 patients with
      signal alterations of the lunate. All MRI examinations were performed on 1.5
      Tesla platforms using dedicated surface coils and an intravenous contrast agent.
      To establish a definitive diagnosis, a total of 252 MRI examinations (49 follow
      ups), 22 CT examinations and 4 arthroscopic studies were obtained in addition to
      the obligatory conventional radiographs. RESULTS: Incorporating all clinical
      data, radiographs and MRI examinations succeeded in assigning a diagnosis in 136
      signal-compromised lunates (67.0 %), whereas additional diagnostic procedures or
      follow-up examinations were required for the definitive diagnosis in 57 cases
      (33.0 %). The most frequent entities were 51 cases of Kienbock's disease (25.1
      %), 47 cases of ulnolunate-(triquetral) impaction syndromes (23.2 %) and 44 cases
      of intra-osseous ganglion cysts (21.7 %). Other pathologies included 23
      degenerative, 19 traumatic and 10 inflammatory changes as well as 9 congenital
      conditions. For MRI assessment of the altered lunate, the most important
      parameters were location and morphology as well as involvement of the articular
      and osseous structures of the carpus. CONCLUSION: The lunate may be affected by
      different pathological states of the wrist. In total, only one quarter of the
      signal-compromised lunate represented Kienboeck's disease.

PMID- 15719298
TI  - [Diagnostic value of MR analysis of cartilaginous lesions compared with
      intraoperative arthroscopy in calcaneal fractures].
AB  - PURPOSE: To determine the diagnostic value of MRI in preoperative analysis and
      classification of cartilaginous lesions - especially of the posterior facet - in
      traumatic calcaneal fractures compared with intraoperative arthroscopy. MATERIALS
      AND METHODS: Twenty-four consecutive patients with traumatic calcaneal fractures
      underwent prospective MRI of the subtalar joint surface using T1- and T2-weighted
      spin echo sequences and fat suppressed 3D gradient echo sequences in semicoronal
      slice orientation (1.5 T MRI). After randomization, the images were analyzed by
      two blinded and independent readers experienced in MRI. The results were compared
      with the intraoperative arthroscopic findings as to location and depth of the
      defects using the Outerbridge classification. RESULTS: We examined 12 calcaneal
      fractures of type 2, 8 of type 3 and 4 of type 4 according to the Sanders
      classification. With respect to principal detection and exact classification, 67
      of 96 (69.8 %) of all arthroscopic verified cartilaginous defects were diagnosed
      correctly by MRI. Disregarding the degree of the defects, 38 of 44 (86.4 %)
      chondral lesions were detected (sensitivity: 86.4 %, specificity: 86.5 %,
      diagnostic accuracy: 86.5 %). Considering the chondral lesions of degrees 3 and 4
      together, the sensitivity was 86.0 %, the specificity 86.8 %, and the diagnostic
      accuracy 86.5 % . Assessing these degrees separately, the sensitivity was only
      33.3 % for degree 3 and 58.1 % for degree 4, whereas the specificity was
      definitely higher with 82.1 % for degree 3 and 89.2 % for degree 4. CONCLUSION:
      The MR detection of cartilaginous defects in calcaneal fractures has a sufficient
      diagnostic accuracy for planning the surgical intervention and assessing the long
      term postsurgical prognosis.

PMID- 15719299
TI  - [MRI of carotid stents: influence of stent properties and sequence parameters on
      visualization of the carotid artery lumen].
AB  - PURPOSE: To evaluate MR artifacts of carotid artery stents and to optimize stent
      properties and sequence parameters. MATERIAL AND METHODS: Four carotid artery
      stents - Wallstent (mediloy), Precise (nitinol), ACCULINK (nitinol) and a stent
      prototype (nitinol) - were investigated in a flow model of the cervical vessels.
      The model was made of silicon tubing and a flow pump that produces realistic flow
      curves of the carotid artery. To investigate the effects of magnetic
      susceptibility and radiofrequency induced shielding artifacts, turbo spin echo
      and gradient echo sequences as well as CE-MRAs were measured. To improve the
      visualization of the stent lumen in a CE-MRA, flip angle as well as geometry and
      covering of the stent prototype were altered. RESULTS: Susceptibility artifacts
      in stents of the carotid artery only influence the lumen visualization at the
      proximal and distal end of the braided mediloy stent. A change of stent coverings
      has no significant influence on radiofrequency artifacts, whereas a reduction in
      linking elements between stent segments and a change in diameter of stent struts
      improves visualization of the stent lumen. By increasing the flip angle in a CE
      MRA, visualization of the stent lumen is possible in both mediloy and nitinol
      stents. CONCLUSION: The choice of stent material and changes in stent geometry as
      well as the optimization of the flip angle of the CE-MRA may reduce
      susceptibility and radiofrequency artifacts, rendering feasible the CE-MRA of a
      stented carotid artery.

PMID- 15719300
TI  - [Does the individual adaptation of standardized speech paradigmas for clinical
      functional magnetic resonance imaging (fMRI) effect the localization of the
      language-dominant hemisphere and of Broca's and Wernicke's areas].
AB  - PURPOSE: Functional magnetic resonance imaging (fMRI) localizes Broca's area (B)
      and Wernicke's area (W) and the hemisphere dominant for language. In clinical
      fMRI, adapting the stimulation paradigms to each patient's individual cognitive
      capacity is crucial for diagnostic success. To interpret clinical fMRI findings
      correctly, we studied the effect of varying frequency and number of stimuli on
      functional localization, determination of language dominance and BOLD signals.
      MATERIALS AND METHODS: Ten volunteers (VP) were investigated at 1.5 Tesla during
      visually triggered sentence generation using a standardized block design. In four
      different measurements, the stimuli were presented to each VP with frequencies of
      1/1 s, (1/2) s, (1/3) s and (1/6) s. RESULTS: The functional localizations and
      the correlations of the measured BOLD signals to the applied hemodynamic
      reference function (r) were almost independent from frequency and number of the
      stimuli in both hemispheres, whereas the relative BOLD signal changes (DeltaS) in
      B and W increased with the stimulation rate, which also changed the
      lateralization indices. The strongest BOLD activations were achieved with the
      highest stimulation rate or with the maximum language production task,
      respectively. CONCLUSION: The adaptation of language paradigms necessary in
      clinical fMRI does not alter the functional localizations but changes the BOLD
      signals and language lateralization which should not be attributed to the
      underlying brain pathology.

PMID- 15719301
TI  - [Percutaneous vertebroplasty -- the role of osseous phlebography].
AB  - PURPOSE: To evaluate the usefulness of osseous phlebography preceding
      percutaneous vertebroplasty. MATERIALS AND METHODS: Seventy-five patients with
      painful osteoporotic (57) or malignant (18) vertebral fractures were treated by
      percutaneous vertebroplasty under fluoroscopic control. Prior to cement
      injection, osseous phlebography was performed, with 247 phlebographic studies
      included in the retrospective correlation with radiographic and CT images.
      Clinical results were assessed by standardized questionnaire. RESULTS: In 69/75
      (92 %) patients, pain and mobility improved and medication needed for pain
      control decreased significantly after vertebroplasty. Two clinically apparent
      complications occurred. The results of osseous phlebography prompted correction
      of the needle position in 34/247 (14 %) of the procedures and cancellation of the
      cement injection in 19/247 (8 %). No complications occurred related to osseous
      phlebography. CT was superior to conventional radiography in detecting extra
      osseous cement leakage (106/247 by CT vs. 63/247 by conventional radiography).
      The cement leakage was asymptomatic in 104/106 (98 %) cases for the duration of
      follow-up. DISCUSSION: Osseous phlebography prior to percutaneous vertebroplasty
      had a significant impact on the procedure in our retrospective study and was able
      to predict the cement distribution in the majority of cases. However,
      phlebography was unable to foresee and therefore prevent 2 clinically relevant
      complications. Complications related to phlebography did not occur.

PMID- 15719302
TI  - [Direct percutaneous radiologic jejunostomy (PR) and duodenostomy: a
      retrospective analysis].
AB  - PURPOSE: To present our experience with direct percutaneous radiologic
      duodenostomy and jejunostomy (PRJ) for alimentation. MATERIALS AND METHODS: A
      retrospective study identified 24 patients who had undergone percutaneous
      jejunostomy or duodenostomy guided by CT and fluoroscopy over a period of 9
      years. Whenever possible, the jejunum was inflated with a 5 French diagnostic
      catheter and jejunopexy was performed using Cope anchors (T-fasteners). A 12 to14
      French locking pigtail drain was inserted for alimentation. In 8 patients,
      percutaneous direct jejunostomy was performed using only fluoroscopy. In 9
      patients, both CT and fluoroscopy were used to guide the jejunostomy. In all 7
      patients who underwent duodenostomy, a combination of CT and fluoroscopy was
      used. The reports were reviewed for complications and the technical success rate.
      The technical success rate was determined. RESULTS: Percutaneous radiologic
      jejunostomy was attempted in 17 patients and failed in 5 patients. PRJ was
      successful in all 8 procedures guided by fluoroscopy and in 4 of 9 procedures
      guided by CT and fluoroscopy. Direct percutaneous duodenostomy guided by CT and
      fluoroscopy was successful in all 7 cases. There were no procedure-related
      laparotomies and no mortality related to the jejunostomy. Minor complications
      were infection of the abdominal wall (n = 1), lingering pain requiring a new
      jejunostomy (n = 1) and aspiration because of persistent reflux (n = 1).
      CONCLUSION: PRJ is a safe procedure even in critically ill patients. It is
      technically difficult and may fail if the jejunum cannot be distended.
      Percutaneous radiologic duodenostomy and jejunostomy are recommended for
      prolonged alimentation of malnourished patients following esophageal or gastric
      surgery.

PMID- 15719303
TI  - [Is the lead-equivalent suited for rating protection properties of lead-free
      radiation protective clothing?].
AB  - PURPOSE: Currently, lead-free x-ray-protective clothing is classified by the
      European production standard EN 61 331-3. To evaluate protective effects of lead
      free materials according to this standard, the certifying offices as well as
      customers solely refer to the lead equivalent (LE). The LE of lead-free
      protective clothing, however, depends on the tube voltage (energy spectrum).
      Therefore, stating a single value for x-ray-protective clothing does not reveal
      the protective efficacy for the complete range of energy as applied in clinical
      practice. Moreover, the method of narrow beam geometry does not account for
      information on secondary radiation (scattered and fluorescent radiation)
      generated within the material. Lead-free materials, however, generate large-scale
      fluorescent radiation, especially for elements with atomic numbers below 60. As a
      consequence, full-scale secondary radiation of a given material can only be
      detected with a broad beam setup. MATERIALS AND METHODS: In accordance with IEC
      61 331-1, we compared commercially available radiation-protective aprons
      manufactured with lead-free or partially lead-free materials with aprons
      manufactured on a lead-oxide basis. In addition to the LE, attenuation ratios and
      dose-build-up-factors under broad beam-conditions were evaluated. RESULTS: In
      comparison with lead-oxide materials, protection efficacy of lead-free materials
      is reduced by up to 70 %, particularly for a tube voltage below 80 kV. Lead
      composite materials (partially lead-free materials) are less affected.
      CONCLUSION: Users and patients wearing lead-free x-ray-protective clothing might
      unknowingly be exposed to a much larger dose than generally assumed. In the
      future, radiation protection rating should exclusively refer to the "attenuation
      ratio", which is based on broad beam geometry and characterizes radiation
      attenuation much more precisely than the lead equivalent.

PMID- 15719304
TI  - [Laser-induced Interstitial thermotherapy (LITT) in hepatic metastases of various
      sizes in an animal model].
AB  - PURPOSE: To assess the effect of laser-induced thermotherapy (LITT) on liver
      metastases of various size from colon carcinoma in an animal model. MATERIALS AND
      METHODS: Liver metastases were implanted in 20 Wistar Albino Glaxo (WAG) rats by
      subcapsular injection of cells from a colorectal strain (CC531) (day 0). The
      animals were divided into two groups with regard to the measured tumor size of
      0.05 - 0.06 cm (3) (group A) and 0.10 - 0.12 cm (3) (group B). On day 14 after
      laparotomy, the tumors were exposed to 1064 nm Nd:YAG laser light at 2 watts for
      5 minutes after intratumoral placement of the laser applicator set. The tumor
      volumes before (V1, at day 13) and after treatment (V2, at day 28) were
      determined by MRI and the mean tumor growth ratio (V2/V1) was calculated.
      RESULTS: The mean tumor volumes V1 and V2 were 0.05 +/- 0.003 cm (3) and 0.23 +/-
      0.016 cm (3) in group A, and 0.11 +/- 0.006 cm (3) and 0.68 +/- 0.037 cm (3) in
      group B. The mean tumor growth ratio (V2/V1) was 4.31 +/- 0.19 in group A and
      6.11 +/- 0.14 in group B. The mean volume of the induced necrosis (0.15 +/- 0.01
      cm (3)) was the same for both groups ( p > 0.05). Compared to group B, liver
      metastases of group A showed a significant slower tumor growth velocity (paired t
      test, p < 0.0001). CONCLUSION: The interventional treatment of large hepatic
      tumors with LITT leads to faster tumor growth compared to smaller lesions.

PMID- 15719305
TI  - [Characterization of an experimental venous thrombus model with MRI, phlebography
      and histology].
AB  - INTRODUCTION: Several magnetic resonance (MR) techniques designed to demonstrate
      the characteristic signal intensity of blood degeneration products of thrombi
      have been suggested, but the effect of thrombus organization on the MR display,
      in particular with regard to its temporal evolution, remains to be determined. It
      is the purpose of this study to develop a stagnation thrombus model in rabbits
      and to characterize thrombus at different ages with two (MR) imaging techniques,
      phlebography and histology. MATERIALS AND METHODS: Venous stagnation thrombi were
      induced in the external jugular veins of rabbits using a minimally invasive
      radiological technique to produce artificial embolic vascular occlusion and
      hypercoagulability. Twenty-five animals were divided into 5 groups of 5 animals,
      and each group underwent 1.5 T MR imaging at 1, 3, 5, 7 and 9 days after thrombus
      induction using a T1-weighted magnetization-prepared rapid gradient-echo sequence
      (MP-RAGE: TR 10.4 msec, TE 4.0 msec, FA 15 degrees ) and a T2-weighted fast low
      angle shot sequence (FLASH: TR 54 msec, TE 18 msec, FA 15 degrees ). The thrombus
      length was measured on the T1-weighted images. Thrombus conspicuity, signal
      intensity, and heterogeneity on T2* weighted images were described using visual
      scales. Radiographic venography and histology served as reference methods.
      RESULTS: Thrombi were successfully induced in all animals. The overall thrombus
      length decreased from 43 +/- 9 (day 1 after induction) to 23 +/- 4 mm (day 9). On
      3D-reconstructions of the T1-weighted images, the visible portion of the true
      thrombus length relative to the overall thrombus length was 0.16 +/- 0.3 (day 1),
      0.24 +/- 0.3 (day 3), 0.38 +/- 0.5 (day 5), 0.06 +/- 0.1 (day 7) and 0.00 (day
      9). Sixteen of 25 thrombi were detectable with the T2*-weighted technique. The
      overall thrombus signal intensity decreased with the age of the thrombus from day
      1 to day 9. The histological evaluation showed that the rabbit thrombi closely
      resemble human thrombi morphologically. CONCLUSIONS: The thrombus model closely
      resembles the human venous stagnation thrombus of different organizational
      stages. With state-of-the-art MRI techniques, thrombi were only partially
      displayed with the visibility depending on thrombus age. The model may be
      suitable for evaluating new and potentially more effective MRI techniques for
      improved thrombus visualization.

PMID- 15719306
TI  - [Comparison of time-oriented cost accounting catalogs to control a department of
      radiology].
AB  - PURPOSE: Within a hospital, the radiology department has taken over the role of a
      cost center. Cost accounting can be applied to analyze the costs for the
      performance of services. By assigning the expenditures of resources to the
      service, the cash value can directly be distributed to the costs of equipment,
      material and rooms. Time-oriented catalogs of services are predefined to
      calculate the number of the employees for a radiology department. Using our own
      survey of time data, we examined whether such catalogs correctly represent the
      time consumed in a radiology department. Only services relevant for the turnover
      were compared. MATERIALS AND METHODS: For 96 primary radiological services
      defined by the score-oriented German fee catalog for physicians (Gebuhrenordnung
      fur Arzte), a ranking list was made for the annual procedures in descending
      frequency order. According to the Pareto principle, the 11 services with the
      highest frequency were chosen and the time consumed for the technical and medical
      services was collected over a period of 2 months. This survey was compared with
      the time-oriented catalogs TARMED and EBM 2000plus. RESULTS: The included 11
      relevant radiological services represented 80.3 % of the annual procedures of our
      radiology department. When comparing the technical services between the time
      oriented catalogs and our own survey, TARMED gives a better description of the
      time consumed in 7 of the 11 services and EMB 2000plus in 3 services. When
      comparing the medical services, TARMED gives a better description of the time
      consumed in 6 of the 11 services and EBM 2000plus in 4 services. When averaging
      all the radiological services, TARMED overestimates the current number of
      physicians necessary for primary reading by a factor of 10.0 % and EBM 2000plus
      by a factor of 2.6 %. CONCLUSION: As to the time spent on performing the relevant
      radiological services, TARMED is slightly superior to describe the radiology
      department of a hospital than EBM 2000plus. For calculating the number of
      physicians necessary for primary reading, EBM 2000plus is superior to TARMED.

PMID- 15719307
TI  - [Referrer satisfaction as a quality criterion: developing an questionnaire for
      measuring the quality of services provided by a radiology department].
AB  - PURPOSE: To develop a questionnaire for measuring referring physician
      satisfaction and to conduct a pilot study in which this questionnaire is given to
      all physicians referring patients to the authors' radiology department. MATERIALS
      AND METHODS: After qualitative pre-testing and adjustment of the prototype
      questionnaire, data were collected using the finalized standardized questionnaire
      comprising 29 indicators rated on a 4-point ordinal scale mailed with a
      personalized cover letter to the total referring physician population of a
      radiology department (n = 727). The replies, rated 1 - 4, were entered into a
      data entry mask for statistical analysis. RESULTS: The response rate was 33.8 %.
      The indicators with the highest satisfaction rating were the range of
      examinations offered ("very satisfied": 79.3 % mean 3.79), the quality of the
      technical equipment used for MRI and CT (79.3 %, 3.79) and mammography (82.5 %,
      3.82), and the quality of the images yielded by these procedures (74.5 %, 3.73
      and 82.2 %, 3.83). Dissatisfaction was relatively high with the indicators "time
      to receipt of the written report" (28.3 % "not very satisfied" or "not at all
      satisfied", mean 2.97), "time to receipt of the X-ray images" (18.2 %, 3.07) and
      "availability of previous findings" (20.9 %, 3.05); satisfaction was higher among
      external referring physicians (p < 0.05). Physicians rated the importance of
      these three indicators as relatively high ("very important": 62.4 %, 54.3 % and
      49.6 %). Other indicators showing a similar level of dissatisfaction were "car
      parking availability" (24.1 %, 3.01), "patient waiting time" (27.4 %, 2.87) and
      "patient environment" (21.2 %, 2.99), although these factors were rated as less
      important ("very important": 33.0 %, 33.7 % and 40.4 %). CONCLUSION: This
      questionnaire constitutes a standardized validated instrument for assessing
      referring physician satisfaction with a radiology department. The data from this
      pilot study highlight areas for potential improvement. Deployment of such a
      questionnaire in different radiology departments could serve to establish best
      practice benchmarks.

PMID- 15719309
TI  - [Synchronous pleomorphic adenoma of the parotid and submandibular glands].

PMID- 15719310
TI  - [Multifocal pulmonary and hepatic epithelioid hemangioendothelioma].

PMID- 15719308
TI  - [Salmonella aortitis. A rare cause of fever and backache].

PMID- 15719311
TI  - [Ruptured dissecting aneurysm in duplication of the distal vertebral artery].

PMID- 15719312
TI  - [Anti-infective drug therapy in ophthalmology--Part 2: viral infections].
AB  - In this review ophthalmological diseases caused by herpes simplex virus,
      varicella zoster virus, Epstein-Barr virus, cytomegaly virus or adenovirus are
      described briefly. The main therapeutic options are discussed placing emphasis
      especially on prospective randomised trials.

PMID- 15719313
TI  - [Retinal angiomatosis].
AB  - BACKGROUND: Retinal capillary hemangioblastomas occur sporadically or as one of
      the manifestations of VHL (von Hippel-Lindau syndrome). In the assessment of
      retinal hemangioblastomas it is necessary to know about VHL, an autosomal
      dominant disease, a multisystem familial tumour syndrome. METHODS: An overview of
      the diagnosis and therapy of VHL is presented. RESULTS: Minimal criteria of the
      syndrome are tumours in one index patient and one of the typical lesions in
      another first-degree relative. Retinal hemangioblastomas were already found in
      children. Only 5 % of patients with VHL present retinal capillary hemangioma
      before the age of 10 years, and most patients present between the ages of 10 and
      40 years. Data suggest that retinal capillary hemangioma is usually manifested by
      the age of 30 years. The VHL gene functions as a tumour suppressor gene and is
      mapped to the short arm of chromosome 3p25. The mapping of a locus for VHL has
      offered the prospect of presymptomatic diagnosis of the disease using DNA
      markers. Small retinal tumours are treated by photocoagulation, big
      hemangioblastomas by cryotherapy. Modern options in treatment of retinal tumours
      are proton therapy, plaque radiotherapy, pars-plana vitrectomy, photodynamic
      therapy, transpupillary thermotherapy and systemic treatment with the vascular
      endothelial growth factor (VEGF) receptor inhibitor, in addition. CONCLUSIONS:
      The interdisciplinary Freiburg VHL study which has been in existence for more
      than 20 years, has shown that an extensive family screening for early detection
      of the disease is necessary. The assessment of the diagnosis in a VHL carrier
      requires close follow-up for multiple and recurrent tumours.

PMID- 15719314
TI  - [Cost-effectiveness of screening for amblyopia].
AB  - BACKGROUND: The effectiveness of a screening program for amblyopia has been
      discussed controversely for several years. While the medical profit is obvious,
      little is known on the cost-effectiveness of such a screening program. METHODS:
      By literature research all important variables were determined: incidence of
      amblyopia, sensitivity of different screening modalities, effectiveness of
      therapy, costs as well as the loss of utility and life quality by an existing
      amblyopia. Based on those data in a simple model the costs of a screening program
      for amblyopia were determined per quality adjusted life year (QALY). The result
      was analyzed for its stability by sensitivity analysis and compared to the costs
      of other therapies. RESULTS: Amblyopia occurs with an incidence of approximately
      2 % (1.3 - 12 %). Most Screening programs reach a sensitivity of 60 - 90 % and
      cause costs of 900 - 1400 Euro per detected case. By appropriate therapy with
      mean costs of 2300 Euro approx. 60 % of the cases obtain useful vision of >
      20/40. However, therapy results vary considerably. After discounting the
      incremental cost-effectiveness ratio (ICER) reaches 7684 Euro/QALY for a
      screening and treatment program for amblyopia. This is well comparable with other
      therapies and accepted to be cost-efficient. Sensitivity analysis yielded 24 700
      Euro/QALY and 57,633 Euro/QAL with higher discounting for worst case scenarios.
      CONCLUSION: Screening for amblyopia meets the basic requirements of cost
      effectiveness.

PMID- 15719315
TI  - [Central and peripheral corneal pachymetry--standard evaluation with the Pentacam
      system].
AB  - BACKGROUND: Corneal thickness measurements are important in refractive surgery,
      for interpretation of IOP and in corneal diseases. The purpose of this study was
      to generate specific standard values for the Pentacam system and to investigate
      the influence of body size, body mass index, body weight, gender and refraction
      on central and peripheral corneal thickness for a more detailed characterization
      of the corneal anatomy. MATERIALS AND METHODS: The Pentacam system is based on a
      180 degrees rotating computer-aided Scheimpflug camera, which generates
      reconstructions of the anterior segment from 12 to 50 single captures. The
      central corneal thickness was calculated from 25 single captures in both eyes of
      182 normal Caucasian subjects (age: 18 - 83 years). The peripheral corneal
      thickness was measured within 3 mm distances at 0 degrees , 90 degrees , 180
      degrees and 270 degrees . All subjects underwent an ophthalmological examination.
      Correlations between corneal thickness and body size, body mass index, body
      weight, gender and refraction were analyzed statistically by non-parametric
      tests. RESULTS: The mean central corneal thickness of all 364 eyes was 534 +/- 36
      microm. Divided into sides it was the same, 534 +/- 36 microm, in the right and
      in the left eyes. The mean central corneal thickness for female subjects was 533
      +/- 40 microm, for males it was 534 +/- 35 microm. Statistically there was no
      proof of any dependence of the central corneal thickness values on the sides,
      gender, age, height, body mass index (BMI) or refraction. However, there was a
      positive significant correlation between central corneal thickness and body
      weight. The peripheral corneal thickness values were lowest in the temporal and
      inferior areas and greatest in the superior and in the nasal areas. In the
      superior and in the nasal areas there was a statistically significant negative
      correlation between age and peripheral corneal thickness. CONCLUSIONS: The
      corneal thickness can be measured touchless with the Pentacam system. The central
      corneal thickness seems to be correlated with the body weight. Anatomical
      features lead to lower peripheral corneal thickness values in the temporal and
      inferior areas than in the nasal and superior areas. In the nasal and in the
      superior areas the corneal thickness seems to decrease with age. Further trials
      are necessary to confirm these findings and to evaluate the precision,
      reproducibilitiy and independence of investigators of the corneal pachymetry with
      the Pentacam system.

PMID- 15719316
TI  - [Intraocular pressure difference in Goldmann applanation tonometry versus a
      transpalpebral tonometer TGDc-01"PRA" in glaucoma patients].
AB  - PURPOSE: The object of this study was to compare intraocular pressure
      measurements obtained with the TGDc-01"PRA", a new, transpalpebral indentation
      tonometer, with those from Goldmann applanation tonometry in normal and
      glaucomatous eyes. METHODS AND PATIENTS: Forty healthy eyes and 185 eyes
      suffering from glaucoma were included in the study. For Goldmann tonometry three
      measurements and for the TGDc-01 ten measurements were performed in a random
      order. All participants were placed in an upright position for all measurements.
      RESULTS: In both groups a systematic increase of intraocular pressure was found
      within the TGDc-01-measurements. Therefore, the first 3 measurements of each
      device were used for further statistical analysis. No learning curve could be
      demonstrated for the TGDc-01-measurement with normal eyes. Within the group of
      normal eyes the mean IOD obtained with the TGDc-01 was 1.84 mmHg lower than the
      mean IOD obtained with Goldmann tonometry (two-sided Student's t-test; P =
      0.003). In the group of glaucomatous eyes, the mean intraocular pressure obtained
      with the Goldmann tonometry was 19.7 +/- 10.1 mmHg, with the TGDC-01 18.1 +/- 7.1
      mmHg (coefficient of correlation r = 0.64, P < 0.001). The mean standard
      deviation of intraocular pressure measurements with Goldmann tonometry was 1.2 +/
      0.9 mmHg, with the TGDc-01 3.1 +/- 2.1 mmHg. TGDc-01-measurements overestimated
      intraocular pressure compared to Goldmann tonometry up to values of 16 mmHg and
      underestimated intraocular pressure at values over 16 mmHg. The difference
      increased by 5.5 mmHg per 10 mmHg Goldmann tonometry. The probability of success,
      defined as TGDc-01-recordings within +/- 3 mmHg of the Goldmann tonometry
      recordings, was less than 53 % between 5 and 20 mmHg and less than 30 % between
      20 and 30 mmHg. Intraocular pressure (Goldmann tonometry) over 30 mmHg was always
      accompanied by TGDc-01-measurements lower than 3 mmHg. CONCLUSION: In eyes with
      elevated intraocular pressure, the TGDc-01"PRA" significantly underestimated the
      intraocular pressure measurement when compared to the gold standard, Goldmann
      tonometry. At present, measurement of the intraocular pressure with the TGDc-01
      should not be used for clinical management of patients with glaucoma.

PMID- 15719317
TI  - [Radial opticus neurotomy].

PMID- 15719318
TI  - [Radial optic neurotomy in ischemic central retinal vein occlusion].
AB  - BACKGROUND: Loss of visual acuity due to ischemic retinal vein occlusion (RVO) is
      still a major problem in ophthalmology. Prognosis is poor and loss of vision is a
      severe risk. New approaches for treatment like systemic fibrinolysis and surgical
      procedures have been suggested. PATIENTS AND METHODS: In a clinical trial 8
      patients with ischemic CRVO underwent surgical decompression. Strict criteria of
      inclusion were maintained. Radial optic neurotomy (RON) was performed 0.25-5
      months after retinal vein occlusion. Follow up-time was 3 months. Visual acuity
      and incidence of typical complications after RVO were the main points of interest
      in our scientific evaluation. RESULTS: Visual acuity improved significantly after
      the surgical procedure. For ischemic CRVO EDTRS charts increased from logMAR 1.0
      (decimal 0.17) to 0.68 (0.30) at 3 months after surgery. Surgical or early
      complications did not occur within 3 months. The recovery of retinal blood flow
      during fluorescein angiography was investigated in 75 % of the patients. A
      resolution of non perfusion-areas could be detected in 50 % of the eyes.
      CONCLUSIONS: For patients with retinal vein occlusion RON seems to be a safe and
      feasible procedure. The results indicate the potential to improve visual acuity
      while typical complications due to surgery or vein occlusion did not occur during
      the first three months.

PMID- 15719319
TI  - [Head-tilt test in unilateral and symmetric bilateral acquired trochlear nerve
      palsy].
AB  - BACKGROUND: The head-tilt phenomenon (difference between the vertical deviations
      with an ipsilateral and contralateral head-tilt by 45 deg. each) occurring in
      patients with a superior oblique palsy has traditionally been explained by the
      lacking contraction of the superior oblique muscle within the synkinetic movement
      of ocular counterrolling. However, using a computer model, Robinson showed that
      the superior oblique palsy itself causes only a relatively small head-tilt
      phenomenon. Adaptive mechanisms amplifying the otolith reflex were suggested to
      explain the increase of the head-tilt phenomenon in the course of time. In order
      to reduce the abnormal head posture required for binocular vision, the otolith
      reflex would be amplified, accepting the greater vertical deviation when the head
      is tilted to the paretic side . QUESTION: If the head-tilt phenomenon were solely
      caused by the lacking contraction of the superior oblique muscle, it should be
      greater in bilateral than in unilateral superior oblique palsies. If an adaptive
      mechanism were acting to reduce the abnormal head posture, the head-tilt
      phenomenon should not be greater, and could even be smaller in bilateral than in
      unilateral superior oblique palsy, because in bilateral (symmetric) trochlear
      nerve palsies the vertical deviation at straight gaze is already small or absent
      without adaptation. PATIENTS AND METHODS: We have carried out a retrospective
      comparison of 10 patients with bilateral symmetric superior oblique palsies and
      10 patients with unilateral superior oblique palsy. In all cases, the palsy was
      acquired and had been present for at least 1 year. RESULTS: The patients with
      bilateral superior oblique palsy had a head-tilt phenomenon ranging from 0 to 7
      degrees (median, 2 deg.). The patients with unilateral superior oblique palsy had
      a head-tilt phenomenon between 2 and 13 degrees (median, 8 deg.). The difference
      was significant (p = 0.0117). CONCLUSIONS: The head-tilt phenomenon is smaller in
      long-standing bilateral symmetric superior oblique palsies than in long-standing
      unilateral superior oblique palsy. This finding supports the hypothesis that in
      unilateral superior oblique palsy, an adaptive mechanism augments the head-tilt
      phenomenon by an amplification of the otolith reflex. However, we presume that
      the amplification of the otolith reflex is only a side effect of the adaptive
      change of the vertical fusional vergence tonus and thus the price of the improved
      vertical fusion, rather than a compensatory mechanism.

PMID- 15719320
TI  - [The surprising finding and removal of a large plastic foreign body through the
      corneal wound from the vitreous cavity with good outcome].
AB  - BACKGROUND: Presented is a patient whose history showed that during a hammer-blow
      on a piece of iron something had flown into his left eye. Clinical investigation
      revealed a 9-mm long, horizontal, paracentrally located, penetrating corneal
      wound. Temporally in the same region the iris was torn in its entire width. The
      lens appeared opaque and seemed to be cut in two parts. Radiological
      investigation revealed no foreign body. METHODS: The operative treatment
      presented a surprise: the white piece, which had been considered to be a part of
      the traumatic cataract, was actually the edge of a large plastic foreign body
      lying in the vitreous cavity. The exciting and complicated procedure of removing
      this 12 x 9 x 2 mm large foreign body through the corneal wound as well as the
      reconstruction of the anterior segment of the eye are demonstrated. RESULTS:
      Seven months after the injury the corneal wound is very tender, the corneal
      sutures have not been removed, and the retina of the aphakic eye is undamaged.
      Visual acuity with a contact lens is 0.6 - 0.7. CONCLUSIONS: Operative treatment
      of patients with a penetrating eye injury is always demanding and difficult and
      requires a lot of experience. Particularly in apparently hopeless cases, an
      optimum primary care is of greatest importance.

PMID- 15719321
TI  - A comparison of linkage disequilibrium patterns and estimated population
      recombination rates across multiple populations.
AB  - Large-scale studies of linkage disequilibrium (LD) have shown considerable
      variation in the extent and distribution of pairwise LD within and between
      populations. Taken at face value, these results suggest that genomewide LD maps
      for one population may not be generalizable to other populations. However, at
      least part of this diversity is due to some undesirable features of pairwise LD
      measures, which are well documented for the D' and r2 measures. In this report,
      we compare patterns of LD derived from pairwise measures with statistical
      estimates of population recombination rates ( rho ) along a 10-Mb stretch of
      chromosome 20 in four population samples, comprising East Asians, African
      Americans, and U.K. and U.S. individuals of western European descent. The results
      reveal the expected variability of D' within and between populations but show
      better concordance in estimates of r2 for the same markers across the population
      samples. Estimates of rho correlate well across populations, but there is still
      evidence of population-specific spikes and troughs in rho values. We conclude
      that it is unlikely that a single haplotype map will provide a definitive guide
      for association studies of many populations; rather, multiple maps will need to
      be constructed to provide the best-possible guides for gene mapping.

PMID- 15719323
TI  - Evaluation of lincomycin in drinking water for treatment of induced porcine
      proliferative enteropathy using a Swine challenge model.
AB  - A single-location, challenge-model study was conducted to evaluate the
      effectiveness of lincomycin against porcine proliferative enteropathy when
      administered through the drinking water at 125 and 250 mg/gallon. The primary
      variables of interest were pig removal rate, diarrhea scores, demeanor scores,
      and abdominal appearance scores. Ancillary performance variables examined
      included average daily feed intake, average daily gain, and feed per gain. After
      a 3-day acclimation period, pigs were challenged on 2 consecutive days with a
      mucosal homogenate containing a total dose of 1.4 x 10(9) cells of Lawsonia
      intracellularis. Five days later, when porcine proliferative enteropathy was well
      established, drinking water medicated with 125 mg (L125) or 250 mg (L250)
      lincomycin/gallon was provided to two groups of pigs for 10 days. Pigs were
      observed for 13 days following the treatment period. A third group of pigs served
      as controls and received unmedicated drinking water throughout the study. The
      L250 group experienced a significantly lower (P < .05) pig removal rate than the
      control group over the 23-day observation period. Additionally, for every primary
      variable, the L250 group experienced a significantly decreased (P < .01) number
      of abnormal days compared with the control group. The L125 group showed a
      significant reduction (P < .05) in abnormal demeanor and abnormal abdominal
      appearance scores compared with controls.

PMID- 15719325
TI  - Comparison of the safety and efficacy of a recombinant feline leukemia virus
      (FeLV) vaccine delivered transdermally and an inactivated FeLV vaccine delivered
      subcutaneously.
AB  - The efficacy of a new recombinant FeLV vaccine (rFeLV), delivered transdermally
      via a needle-free delivery device was compared to that of an inactivated FeLV
      vaccine (FeLV-k), administered subcutaneously, with a conventional needle and
      syringe. Kittens were immunized with either rFeLV (0.25 ml, transdermal) or FeLV
      k (1 ml, subcutaneous); or they were sham-vaccinated with physiologic saline
      (0.25 ml, transdermal). Two vaccinations were administered 21 days apart.
      Injection sites were monitored for any acute or subacute reactions relative to
      vaccine administration. Four weeks following the final vaccination, all cats were
      subject to oro-nasal FeLV challenge. Blood was collected for determination of
      FeLV antigenemia (p27) at weekly intervals beginning three weeks post-challenge.
      All of the vaccinated cats from both groups resisted FeLV challenge; and 90% of
      the control cats developed persistent FeLV antigenemia in response to challenge.
      No acute or persistent injection site reactions were observed. The rFeLV,
      delivered transdermally, provides protection against persistent FeLV antigenemia
      following a robust challenge that is equivalent to that of FeLV-k.

PMID- 15719324
TI  - The anamnestic serologic response to vaccination with a canarypox virus-vectored
      recombinant West Nile virus (WNV) vaccine in horses previously vaccinated with an
      inactivated WNV vaccine.
AB  - A new recombinant West Nile virus (WNV) vaccine has been licensed for use in
      horses. Prior to the availability of the recombinant vaccine in 2004, the only
      equine WNV vaccine available on the market had been an inactivated vaccine. Since
      the recombinant vaccine only expresses selected viral genes, the question could
      be posed as to whether a single dose of the recombinant vaccine would be
      effective in producing an anamnestic serologic response in horses previously
      vaccinated with an inactivated WNV vaccine. In this study we demonstrate that
      vaccination of horses with a canarypox-vectored recombinant vaccine, under field
      conditions, results in a marked anamnestic response in horses previously
      vaccinated with an inactivated WNV vaccine.

PMID- 15719326
TI  - Potential growth inhibitory effect of maitake D-fraction on canine cancer cells.
AB  - The postulated anticancer effect of D-fraction, the bioactive extract of maitake
      mushroom, on three types (CF33, CF21, and CL-1) of canine cancer cells was
      evaluated. The effect of D-fraction on several human cancer cells was also
      investigated. The effect of other beta-glucan products was likewise examined. D
      fraction was highly effective on the canine cancer cells, either potently
      inhibiting cell growth or directly killing cells. Similar effects were also
      demonstrated in certain human cancer cells. However, other beta-glucan products
      relevant to D-fraction had no such effects on canine cancer cells. Therefore, D
      fraction is a potent natural agent that could be useful in treating canine
      cancers as well as other veterinary cancers.

PMID- 15719322
TI  - Analysis of families in the multiple autoimmune disease genetics consortium
      (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune
      phenotypes.
AB  - Autoimmune disorders constitute a diverse group of phenotypes with overlapping
      features and a tendency toward familial aggregation. It is likely that common
      underlying genes are involved in these disorders. Until very recently, no
      specific alleles--aside from a few common human leukocyte antigen class II genes-
      had been identified that clearly associate with multiple different autoimmune
      diseases. In this study, we describe a unique collection of 265 multiplex
      families assembled by the Multiple Autoimmune Disease Genetics Consortium
      (MADGC). At least two of nine "core" autoimmune diseases are present in each of
      these families. These core diseases include rheumatoid arthritis (RA), systemic
      lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS),
      autoimmune thyroid disease (Hashimoto thyroiditis or Graves disease), juvenile
      RA, inflammatory bowel disease (Crohn disease or ulcerative colitis), psoriasis,
      and primary Sjogren syndrome. We report that a recently described functional
      single-nucleotide polymorphism (rs2476601, encoding R620W) in the intracellular
      tyrosine phosphatase (PTPN22) confers risk of four separate autoimmune phenotypes
      in these families: T1D, RA, SLE, and Hashimoto thyroiditis. MS did not show
      association with the PTPN22 risk allele. These findings suggest a common
      underlying etiologic pathway for some, but not all, autoimmune disorders, and
      they suggest that MS may have a pathogenesis that is distinct from RA, SLE, and
      T1D. DNA and clinical data for the MADGC families are available to the scientific
      community; these data will provide a valuable resource for the dissection of the
      complex genetic factors that underlie the various autoimmune phenotypes.

PMID- 15719327
TI  - Pharmacokinetics of subcutaneous selenium in adult llamas.
AB  - Selenium (Se) deficiency disease has been described in camelids and only clinical
      data is available for administration of parenteral Se supplements. This study
      investigated the pharmacokinetic effects of subcutaneous Se injection (0.1 mg/kg)
      in llamas fed a diet adequate in Se. Absorption of Se was rapid with peak whole
      blood Se concentration at the first sampling time. Significant differences in
      whole blood Se concentration from before injection of Se were not found past 2
      days after Se injection. Parenteral Se is unlikely to have a long-term effect on
      whole blood Se concentration in llamas fed adequate dietary Se.

PMID- 15719328
TI  - Chronic kidney disease in the general population.
AB  - End-stage kidney disease (ESKD), defined as the need for dialysis, receipt of a
      transplant, or death from chronic kidney failure, generally affects fewer than 1%
      of the population. However ESKD is the end result of chronic kidney disease
      (CKD), a widely prevalent but often silent condition with elevated risks of
      cardiovascular morbidity and mortality and a range of metabolic complications. A
      recently devised classification of CKD has facilitated prevalence estimates that
      reveal an "iceberg" of CKD in the community, of which dialysis and transplant
      patients are the tip. Hypertension, smoking, hypercholesterolemia, and obesity,
      currently among the World Health Organization's (WHO's) top 10 global health
      risks, are strongly associated with CKD. The factors, together with increasing
      diabetes prevalence and an aging population, will result in significant global
      increases in CKD and ESKD patients. Treatments now available effectively reduce
      the rate of progression of CKD and the extent of comorbid conditions and
      complications. The challenges are (1) to intervene effectively to reduce the
      excess burden of cardiovascular morbidity and mortality associated with CKD, (2)
      to identify those at greatest risk for ESKD and intervene effectively to prevent
      progression of early CKD, and (3) to ultimately introduce cost-effective primary
      prevention to reduce the overall burden of CKD. The vast majority of the global
      CKD burden will be in developing countries, and policy responses must be both
      practical and sustainable in these settings.

PMID- 15719329
TI  - Kidney and kidney related chronic diseases in South Africa and chronic disease
      intervention program experiences.
AB  - The burden of chronic kidney disease (CKD) is rising in the world and the
      greatest burden is likely in developing countries such as South Africa (SA). This
      burden is related to the increase of 130% in noncommunicable diseases (NCD) such
      as diabetes and hypertension. SA has an additional burden of human
      immunodeficiency virus (HIV), which has infected 19.9% of adults and contributes
      to 30% of deaths. NCDs remain the major causes of death (37%). Hypertension is
      considered as a cause of end-stage renal disease (ESRD) in 34.6% of Blacks, 4.3%
      Whites, 20.9% of mixed race people, and 13.9% of Indians. Diabetes is believed to
      occur in 10% to 16% of South Africans. These risk factors, together with a high
      HIV/CKD burden (8%), result in a large burden of CKD. Other nontraditional risk
      factors, such as low birth weight, must also be considered. Despite rates of ESRD
      suspected to be about 400 per million population (pmp), only 99 pmp receive renal
      replacement therapy (RRT). Novel methods have to be established in the developing
      world to tackle the NCD and communicable disease burden. This article
      investigates the option of an integrated approach to chronic diseases as an
      answer to some of this burden. Both an urban-based and a rural-based NCD
      prevention and treatment program are reviewed.

PMID- 15719330
TI  - Cost-effectiveness analysis of a kidney and cardiovascular disease treatment
      program in an Australian Aboriginal population.
AB  - The objective of the study was to assess, from a health service perspective,
      whether a systematic program to modify kidney and cardiovascular disease reduced
      the costs of treating end-stage kidney failure. The participants in the study
      were 1,800 aboriginal adults with hypertension, diabetes with microalbuminuria or
      overt albuminuria, and overt albuminuria, living on two islands in the Northern
      Territory of Australia during 1995 to 2000. Perindopril was the primary treatment
      agent, and other medications were also used to control blood pressure. Control of
      glucose and lipid levels were attempted, and health education was offered.
      Evaluation of program resource use and costs for follow-up periods was done at 3
      and 4.7 years. On an intention-to-treat basis, the number of dialysis starts and
      dialysis-years avoided were estimated by comparing the fate of the treatment
      group with that of historical control subjects, matched for disease severity, who
      were followed in the before the treatment program began. For the first three
      years, an estimated 11.6 person-years of dialysis were avoided, and over 4.7
      years, 27.7 person-years of dialysis were avoided. The net cost of the program
      was 1,210 dollars more per person per year than status quo care, and dialyses
      avoided gave net savings of 1.0 million dollars at 3 years and 3.4 million
      dollars at 4.6 years. The treatment program provided significant health benefit
      and impressive cost savings in dialysis avoided.

PMID- 15719331
TI  - Factors influencing reported rates of treated end-stage renal disease.
AB  - Rates of treated end-stage renal disease have risen relentlessly throughout the
      Western world over the past 30 years, with little indication of a slowing in the
      rate. This increase has a number of causes, such as important trends in disease
      prevalence, changing population structure, and changing treatment patterns. A
      number of biases also affect measured rates of renal replacement therapy. These
      biases include lead-time and length bias, as well as classification bias. A
      further important effect will be changes in competing risks, in particular,
      changing mortality from cardiovascular disease. We examine the effects of these
      factors by analyzing data from the Australia and New Zealand Dialysis and
      Transplant (ANZDATA) Registry. Rates of treated ESRD have risen steadily over the
      past 30 years, which appears to be the result of several factors. Rates among
      older people have increased particularly, as have rates among Australian and New
      Zealand indigenous peoples. Higher rates are also seen among some immigrant
      groups. Accentuating the effect of these changing rates are changes in the
      structure of the population and the tendency to commence treatment earlier. The
      increase in rates of ESRD treatment is often ascribed to an explosion of kidney
      disease. Although a major contribution comes from increasing disease prevalence,
      understanding the implications of this increase requires comprehension of a
      number of other factors.

PMID- 15719332
TI  - Interfaces between cardiovascular and kidney disease among Aboriginal
      Australians.
AB  - Rates of kidney disease among several indigenous groups have been shown to be
      substantially higher than corresponding non-indigenous groups. This excess has
      been clearly shown among Aboriginal Australians with respect to both end-stage
      kidney disease and early kidney disease. Rates of cardiovascular disease among
      Aboriginal Australians are also very high, as are rates of diabetes, smoking, and
      possibly overweight and obesity. These factors have been traditionally linked
      with cardiovascular and renal disease as part of a broader "metabolic syndrome."
      However, the links and interfaces between cardiovascular and kidney disease in
      this environment extend beyond these "traditional" factors. The factors
      associated with atherosclerosis have expanded in recent years to include markers
      of inflammation, some infection, antioxidants, and other "non-traditional" risk
      factors. Given the high rates of acute infection and poor living conditions
      endured by many indigenous people, one might expect these "non-traditional" risk
      factors to be highly prevalent. In this review, we explore the relationships
      between markers of inflammation, some serological markers of infection, and other
      selected markers and both cardiovascular and renal disease. In doing so, we
      demonstrate links between kidney and cardiovascular disease at a number of
      levels, beyond the "traditional" cardiovascular/renal risk factors. Many of these
      factors are beyond the control of the individual or even community; addressing
      these issues a broader focus and biopsychosocial model.

PMID- 15719333
TI  - The influence of obesity on the development and survival outcomes of chronic
      kidney disease.
AB  - The prevalence of obesity, defined as a body mass index (BMI) greater than 30
      kg/m2 , has more than doubled in many Western countries over the past 2 decades
      and has become a major public health challenge. This epidemic of obesity in
      developed countries has been matched closely by alarming increases in the
      incidence of diabetes mellitus, hypertension, chronic kidney disease (CKD), and
      cardiovascular disease. However, the exact role that increased body size plays in
      the development of nephropathy and its subsequent contribution to cardiovascular
      morbidity and mortality remain unclear. For example, whether obesity per se is a
      risk factor for CKD independent of diabetes mellitus and hypertension is
      uncertain. Moreover, in patients with end-stage kidney disease, strong evidence
      suggests that obesity may paradoxically enhance patient survival. This review
      will focus on the evidence for obesity as an independent risk factor for the
      development and progression of CKD and as a paradoxical survival factor in
      patients with end-stage kidney failure. Possible mechanisms underlying these
      observed associations will be discussed.

PMID- 15719334
TI  - Chronic kidney disease and life course socioeconomic status: a review.
AB  - Socioeconomic status (SES) may modify the effect of well-established risk factors
      on the development of kidney disease. Yet, recently, a paradigm shift has
      occurred with an emphasis on the direct effect of SES on the development of
      disease. This article covers the role SES may play in initiating and promoting
      chronic kidney disease (CKD) in the United States, with an emphasis on life
      course SES. The literature on SES and kidney disease is discussed. Life-course
      and social epidemiology approaches are described. Salient risk factors and
      markers that are associated with both SES and kidney disease early in life
      include diet, birth weight, and infant mortality. Risk factors associated with
      individual SES later in life include diabetes mellitus, hypertension, diet,
      smoking, alcohol, drug use, occupational and environmental exposures, infection,
      and access to health care. An argument is made for incorporating area-level SES
      measures. Future research should incorporate both individual and area-level SES
      and be placed in the context of the life course.

PMID- 15719335
TI  - Kidney and related chronic disease profiles and risk factors in three remote
      Australian Aboriginal communities.
AB  - Morbidities and deaths from noncommunicable chronic diseases are greatly
      increased in remote Australian Aboriginal communities, but little is known of the
      underlying community-based health profiles. We describe chronic-disease profiles
      and their risk factors in 3 remote communities in the Northern Territory.
      Consenting adults (18+ years of age) in 3 communities participated in a brief
      history and examination between 2000 and mid-2003 as part of a systematic program
      to improve chronic-disease awareness and management. Participation was 67%, 128%,
      and 62% in communities A, B, and C, respectively with a total of 1070 people
      examined. Current smokers included 41% of females and 72% of males. Most men were
      current drinkers, but most women were not. Parameters of body weight differed
      markedly by community, with mean body mass index (BMI) varying from 21.4 to 27.9
      kg/m2 . Rates of chronic diseases were excessive but differed markedly; an almost
      threefold difference in the likelihood of any morbidity existed between
      communities A and C. Rates increased with age, but the greatest numbers of people
      with morbidities were in the middle-aged group. Most people had multiple
      morbidities with tremendous overlap. Hypertension and kidney disease appear to be
      early manifestations of the integrated chronic-disease syndrome, while diabetes
      is a late manifestation or complication. Substantial numbers of new cases of
      disease were identified by testing, and blood pressure improved in treated people
      with hypertension. Wide variations occur in body habitus, risk factors, and
      chronic-disease rates among communities, but an overwhelming need for effective
      smoking interventions exists in all. Systematic screening is useful in
      identifying high-risk individuals, most at early treatable stages there. Findings
      are very important for estimating current treatment needs, future burdens of
      disease, and for needs-based health services planning. Resources required will
      vary according to the burden of disease.

PMID- 15719336
TI  - The elderly patient with chronic kidney disease.
AB  - The elderly are a fast growing population in the United States, and they have a
      high prevalence of chronic kidney disease. The elderly are particularly
      susceptible to kidney damage from age-related declines in glomerular filtration
      as well as kidney damage from chronic disease states such as diabetes mellitus,
      hypertension, glomerular, and tubulointerstitial disorders. A significant number
      of elderly individuals are reaching end-stage renal disease that require renal
      replacement therapy. This expanding population provides a challenge for health
      care providers because the elderly are often referred late to a nephrologist,
      have a shortened survival on renal replacement therapy as compared with younger
      individuals, and suffer from more comorbidities such as cardiovascular disease,
      malnutrition, and hearing and visual disabilities. The elderly also have
      difficulties with dialysis vascular access and often are not candidates for renal
      transplantation. Despite these obstacles, age alone is not a justification for
      withholding diagnostic or therapeutic interventions, because many elderly
      individuals have an improvement in their quality of life and social support once
      their kidney disease is identified and treated.

PMID- 15719337
TI  - Role of oxidative stress in age-associated chronic kidney pathologies.
AB  - The kidneys exhibit age-associated deterioration in function via a loss of 20% to
      25% kidney mass, particularly from the renal cortex and increased fibrosis.
      Oxidative stress has been found to mediate age-associated renal cell injury and
      cell death, particularly apoptosis. Oxidative stress results from an imbalance
      between the levels of free radicals generated during aerobic metabolism,
      inflammation, and infection and the safe breakdown of these species by endogenous
      and exogenous scavengers. Other factors may influence these pathologies. For
      example, growth hormone and caloric restriction have been shown to influence life
      span, although neither method of prolonging life is likely to find general
      acceptance in humans. Some genetic knockout models offer promise; for example,
      knockout of the p66 isoform of the Shc gene in mice increases life span by 30%,
      but appetite, size, and fertility are retained. Whether the increase in life span
      is via increased kidney health is not yet clear, but decreasing the age-related
      renal pathologies will no doubt aid in increasing life span and health in
      general. This review looks at the role and modulation of factors that influence
      life span, in particular modulation of oxidative stress, with particular
      relevance to age-related renal pathologies.

PMID- 15719338
TI  - Deprivation and dialysis: pathways to kidney failure in Australian Aborigines.
AB  - Rates of end-stage renal disease among Australian Aboriginal people have been
      increasing over the past 2 decades, particularly in the northern and more remote
      areas of Australia, and especially in disadvantaged communities. Proteinuria
      predicts the rate of loss of kidney function; it is common in young adults and
      virtually universal in those over 50 years of age. Cumulative independent risk
      factors include low birth weight, recurrent skin infections, adult obesity,
      diabetes or its precursors, smoking, excessive alcohol intake, and a family
      history of renal disease. A plausible theory is that intrauterine malnutrition
      permanently reduces total nephron numbers, which are then overworked in adulthood
      by the metabolic stresses of obesity (from excess alcohol and poor diet), by
      higher blood pressures, and by infections, while starved of blood supply because
      of smoking. Although kidney disease is often only detected when already well
      established, active medical intervention offers great rewards. Control of blood
      pressure (preferentially using angiotensin-converting enzyme (ACE) inhibitors and
      angiotensin-II receptor blockers (AIIRBs) in combination) can often stop or even
      reverse kidney damage, even if ongoing diabetes control is poor. Adequately
      funded kidney health programs with active Aboriginal health worker involvement
      are enormously cost-effective: tight blood pressure control at least halves the
      rate of disease progression, and every year of dialysis deferred for 1 patient
      could fund the appointment of 2 health workers. Addressing the underlying social
      causes for this epidemic is critical.

PMID- 15719339
TI  - Emergence of quantification in clinical investigation and the quest for certainty
      in therapeutics: the road from Hammurabi to Kefauver.
AB  - Throughout most of history, medical knowledge was descriptive in nature and
      derived from the work of individual investigators of independent mind pursuing
      careful but often chance observations. Using deductive reasoning, these findings
      were then generalized, authoritatively presented, and dogmatically promulgated.
      This, coupled with firmly grounded principles of divine determinism, precluded
      any serious consideration of randomness, even when variations from recorded, but
      erroneous, statements were actually observed. Although probability remained an
      integral component of diagnosis and therapy, it was only as an attribute of
      opinion and not one supported by numbers. The gradual erosion of this edifice
      began during the scientific revolution of the seventeenth century that led to the
      burgeoning of the sciences basic to medicine. Although clinicians applauded these
      contributions, they failed to apply the inductive method of investigation to the
      study of disease or to therapy. The "numerical method" of Pierre Louis (1787
      1872) first introduced systematic quantification into medicine during the first
      half of the nineteenth century. Analysis of quantifiable data found its principal
      application in epidemiology, which flourished during the second half of the
      nineteenth century. The subsequent adoption of probability calculus for the
      analysis of quantifiable data, during the first half of the twentieth century,
      refined the process further and led to the gradual emergence of medical
      statistics, with a distinct role in clinical research. The mathematical precision
      provided by quantification and statistical analysis established certainty in
      medicine and ultimately changed the conjectural art of clinical practice into a
      disciplined science founded on clinical investigation, the very basis of present
      day, evidence-based medicine.

PMID- 15719340
TI  - Outcomes research in nutrition and chronic kidney disease: perspectives, issues
      in practice, and processes for improvement.
AB  - Despite greater access to health care and advances in medicine and technology,
      the morbidity and mortality among patients diagnosed with chronic kidney disease
      (CKD) remain unacceptably high. Discrepancies in patient care outcomes exist
      between the United States and other industrialized countries and are partly
      explained by variances reported in clinical practice. Outcomes research (OR) has
      been the primary methodology used to more fully explore the root causes for the
      practice variation and to uncover which indicators have the greatest impact.
      Research has established the relationships between early diagnosis and treatment,
      cardiovascular disease, quality of life, and malnutrition with morbidity and
      mortality rates among patients with kidney disease. Although nutrition parameters
      are predictive of mortality, they are complex to understand and even more
      difficult to improve, largely because of the effects of the inflammatory process
      and the lack of a direct measure that defines nutritional status. Future OR
      projects must focus on specific nutrition-related outcomes and the effectiveness
      of intervention, as these outcomes can establish clinical guidelines, lead to
      changes in practice, and create more controlled clinical trials that continue to
      search for answers to questions on the impact of nutrition and others.

PMID- 15719341
TI  - The involuntarily discharged dialysis patient: conflict (of interest) with
      providers.

PMID- 15719343
TI  - Medicare and rural kidney medicine.

PMID- 15719344
TI  - Changes in B-type natriuretic peptide levels in hemodialysis and the effect of
      depressed left ventricular function.
AB  - B-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted
      by the cardiac ventricles in response to volume expansion, pressure overload, and
      resultant increased wall tension. Previous research has shown elevated BNP levels
      in patients with volume overload caused by end-stage renal disease (ESRD). This
      pilot study was designed to describe the relative reduction in BNP that occurs as
      a result of hemodialysis (HD) in relation to baseline left ventricular function.
      Hemodialysis patients (n = 34) with ESRD were enrolled in a prospective manner.
      All patients had blinded serum BNP levels measured at the initiation and
      termination of HD. Levels of BNP were also measured in the dialysate and any
      residual urine, if available. In addition, monthly urea reduction ratio (URR) and
      Kt/V were obtained. The most recent measurement of left ventricular ejection
      fraction (LVEF) by any method was obtained from chart review. The BNP reduction
      ratio (BNPRR) was calculated by the following expression: pre-BNP-post-BNP/pre
      BNP. The mean age was 50.8 years, 50.0% were male, and 55.9% were African
      American. A mean of 3239.4 mL of fluid was removed during HD. The mean pre-BNP,
      post-BNP, and change in BNP were 556.3 +/- 451.5 pg/mL, 538.6 +/- 488.3 pg/mL,
      and -17.6 +/-147.0 pg/mL. Of the 27 patients who had both pre-BNP and post-BNP
      values in the measurable range (< 1,300 pg/mL), BNP rose in 9 (33.3%) and fell in
      18 (66.7%). The BNPRR had the following correlations: volume removed, r = -0.33,
      P = .07; Kt/V, r = -0.51, P = .01; URR, r = -0.34, P = .09; and change in body
      weight, r = -0.33, P = .07. The BNPRR was not correlated with time on dialysis or
      change in blood pressure. A total of 20 patients had LVEF recorded and post-BNP
      levels in the measurable range. For this group, the BNPRR values stratified by
      lowest to highest LVEF group were 4.6%, 19.1%, and 21.8%; P = .95 for trend. The
      BNP values were elevated in ESRD patients and decreased slightly during HD. This
      change was more pronounced in patients with normal or mildly impaired LVEF. The
      BNPRR correlated with the volume removed, change in body weight, and Kt/V. Future
      research with the BNPRR as a potential marker of the adequacy of volume removal
      in HD is warranted.

PMID- 15719346
TI  - A widely distributed bacterial pathway for siderophore biosynthesis independent
      of nonribosomal peptide synthetases.

PMID- 15719347
TI  - Ring-closing metathesis of C-terminal allylglycine residues with an N-terminal
      beta-vinyl-substituted phosphotyrosyl mimetic as an approach to novel Grb2 SH2
      domain-binding macrocycles.
AB  - Ring-closing metathesis (RCM) of peptides often requires insertion of
      allylglycines at the intended sites of ring juncture, which can result in the
      displacement of residues that are needed for biological activity. This type of
      side-chain deletion can be avoided by appending beta-vinyl substituents onto the
      parent residues at the intended sites of ring juncture, thereby effectively
      converting them into functionalized allylglycine equivalents. Such an approach
      has been previously applied in modified form to growth-factor receptor bound 2
      (Grb2) SH2 domain-binding peptides by using an N-terminal beta-vinyl
      functionalized phosphotyrosyl mimetic and C-terminal 2-allyl-3-aryl-1
      propanamides that lacked the alpha-carboxyl portion of allylglycine residues.
      These C-terminal moieties involved lengthy synthesis and once prepared, required
      an individual total synthesis of each final macrocycle. Work reported herein
      significantly enhances the versatility of the original approach through the use
      of C-terminal allylglycine amides that can be prepared from commercially
      available L- and D-allylglycines and suitable amines. This methodology could be
      generally useful where macrocylization is desired with maintenance of
      functionality at a site of ring juncture.

PMID- 15719349
TI  - Asymmetric multicomponent reactions (AMCRs): the new frontier.
AB  - Asymmetric multicomponent reactions involve the preparation of chiral compounds
      by the reaction of three or more reagents added simultaneously. This kind of
      addition and reaction has some advantages over classic divergent reaction
      strategies, such as lower costs, time, and energy, as well as environmentally
      friendlier aspects. All these advantages, together with the high level of
      stereoselectivity attained in some of these reactions, will force chemists in
      industry as in academia to adopt this new strategy of synthesis, or at least to
      consider it as a viable option. The positive aspects as well as the drawbacks of
      this strategy are discussed in this Review.

PMID- 15719350
TI  - Trifluoromethylated endohedral metallofullerenes: synthesis and characterization
      of Y@C82(CF3)5.

PMID- 15719348
TI  - Directed evolution of an amine oxidase for the preparative deracemisation of
      cyclic secondary amines.

PMID- 15719351
TI  - Synthesis of hexa- and dodecanuclear organoaluminum ring structures incorporating
      the "magic" Ph2C(X) Group (X=O-, NH-).

PMID- 15719352
TI  - Comparison of FeIV=O heme and non-heme species: electronic structures, bonding,
      and reactivities.

PMID- 15719353
TI  - Points to consider: the roles of surveillance and epidemiology in advancing drug
      safety.

PMID- 15719354
TI  - Small proportions: what to report for confidence intervals?
AB  - PURPOSE: It is generally agreed that a confidence interval (CI) is usually more
      informative than a point estimate or p-value, but we rarely encounter small
      proportions with CI in the pharmaco-epidemiological literature. When a CI is
      given it is sporadically reported, how it was calculated. This incorrectly
      suggests one single method to calculate CIs. To identify the method best suited
      for small proportions, seven approximate methods and the Clopper-Pearson Exact
      method to calculate CIs were compared. METHODS: In a simulation study for 90-, 95
      and 99%CIs, with sample size 1000 and proportions ranging from 0.001 to 0.01,
      were evaluated systematically. Main quality criteria were coverage and interval
      width. The methods are illustrated using data from pharmaco-epidemiology studies.
      RESULTS: Simulations showed that standard Wald methods have insufficient coverage
      probability regardless of how the desired coverage is perceived. Overall, the
      Exact method and the Score method with continuity correction (CC) performed best.
      Real life examples showed the methods to yield different results too.
      CONCLUSIONS: For CIs for small proportions (pi < or = 0.01), the use of the Exact
      method and the Score method with CC are advocated based on this study.

PMID- 15719355
TI  - A 4'-phosphopantetheinyl transferase mediates non-ribosomal peptide synthetase
      activation in Aspergillus fumigatus.
AB  - Aspergillus fumigatus is a significant human pathogen. Non-ribosomal peptide
      (NRP) synthesis is thought to be responsible for a significant proportion of
      toxin and siderophore production in the organism. Furthermore, it has been shown
      that 4'-phosphopantetheinylation is required for the activation of key enzymes
      involved in non-ribosomal peptide synthesis in other species. Here we report the
      cloning, recombinant expression and functional characterisation of a 4'
      phosphopantetheinyl transferase from A. fumigatus and the identification of an
      atypical NRP synthetase (Afpes1), spanning 14.3 kb. Phylogenetic analysis has
      shown that the NRP synthetase exhibits greatest identity to NRP synthetases from
      Metarhizium anisolpiae (PesA) and Alternaria brassicae (AbrePsy1). Northern
      hybridisation and RT-PCR analysis have confirmed that both genes are expressed in
      A. fumigatus. A 120 kDa fragment of the A. fumigatus NRP synthetase, containing a
      putative thiolation domain, was cloned and expressed in the baculovirus
      expression system. Detection of a 4'-phosphopantetheinylated peptide (SFSAMK)
      from this protein, by MALDI-TOF mass spectrometric analysis after coincubation of
      the 4'-phosphopantetheinyl transferase with the recombinant NRP synthetase
      fragment and acetyl CoA, confirms that it is competent to play a role in NRP
      synthetase activation in A. fumigatus. The 4'-phosphopantetheinyl transferase
      also activates, by 4'-phosphopantetheinylation, recombinant alpha-aminoadipate
      reductase (Lys2p) from Candida albicans, a key enzyme involved in lysine
      biosynthesis.

PMID- 15719356
TI  - Inhibition of fibril formation of Abeta by guanidiniocarbonyl pyrrole receptors.

PMID- 15719357
TI  - The first studies of a tetrathiafulvalene-sigma-acceptor molecular rectifier.
AB  - Langmuir-Blodgett monolayers of a donor-acceptor diad TTF-sigma
      (trinitrofluorene) (8) with an extremely low HOMO-LUMO gap (0.3 eV) have been
      used to create molecular junction devices that show rectification behavior. By
      virtue of structural similarities and position of molecular orbitals, 8 is the
      closest well-studied analogue of the model Aviram-Ratner unimolecular rectifier
      (TTF-sigma-TCNQ). Compressing the monolayer results in aligning the molecules,
      and is followed by a drastic increase in the rectification ratio. The direction
      of rectification depends on the electrodes used and is different in n-Si/8/Ti and
      Au/8/C16H33S-Hg junctions. The molecular nature of such behavior was corroborated
      by control experiments with fatty acids and by reversing the rectification
      direction with changing the molecular orientation (Au/D-sigma-A versus Au/A-sigma
      D).

PMID- 15719358
TI  - An efficient ionization method of electrospray mass spectrometry: the development
      of an aromatic-cored matrix that wraps labile metal complexes through molecular
      recognition.
AB  - Compound 1a, which possesses a triphenylene core and six tetraethyleneoxide side
      chains, shows efficient ionization of M(II)-containing (M=Pd, Pt) complexes in
      electrospray ionization mass spectrometry (ESI-MS). The molecular ion peaks [M]+,
      which are hardly detected under common ESI-MS conditions, are clearly observed as
      their [M x (1a)n]+ (n=1-4) adducts. UV-visible and NMR studies reveal that the
      electron-rich triphenylene core of 1a binds to the electron-deficient frameworks
      of the M(II) complexes in solution, giving rise to charge transfer (CT)
      complexes. We suggest that 1a stabilizes the complexes and promotes efficient
      ionization through unique donor-acceptor molecular recognition.

PMID- 15719359
TI  - Synthesis and structural metastability of CdTe nanowires.
AB  - A new organometallic preparation method is described for CdTe nanowires with a
      high aspect ratio and a predominantly metastable wurtzite phase. The optical and
      morphological properties of the resulting nanowires were studied, as well as the
      influence of elevated temperatures on the crystallographic properties. A phase
      transition from wurtzite to sphalerite was observed at about 500 degrees C. The
      results show that the wurtzite phase is stabilized by the synthetic method and
      the surfactants.

PMID- 15719360
TI  - New trends in the chemistry of iron(III) citrate complexes: correlations between
      X-ray structures and solution species probed by electrospray mass spectrometry
      and kinetics of iron uptake from citrate by iron chelators.
AB  - Despite the crucial role of "iron(III) citrate systems" in the iron metabolism of
      living organisms (bacteria as well as plants or mammals), the coordination
      chemistry of ferric citrate remains poorly defined. Variations in the
      experimental conditions used for the preparation of so-called ferric citrates
      (iron salt, Fe:cit molar ratio, base, pH, temperature, solvent) lead to several
      different species, which are in equilibrium in solution. To date, six different
      anionic complexes have been structurally characterized in the solid state, by
      ourselves or others. In the work described herein, we have established the
      experimental conditions leading to each of them. Five were obtained from aqueous
      solution. With the exception of a nonanuclear species (of which fragments have
      been detected), all were identified in aqueous solution on the basis of
      electrospray ionization mass spectrometry. In addition, the spectra revealed a
      new trinuclear species, which could not be crystallized. Kinetic studies of iron
      uptake from citrate species by iron chelators confirmed the results indicated by
      the ESI-MS studies. These studies also allowed the relative molar fraction of
      mononuclear versus polynuclear complexes to be determined, which depends on the
      Fe:cit molar ratio.

PMID- 15719361
TI  - Capillary zone electrophoresis of amino acids on a hybrid poly(dimethylsiloxane)
      glass chip.
AB  - Poly(dimethylsiloxane) (PDMS)-PDMS and hybrid PDMS-glass devices have been
      characterized and compared in terms of current-voltage linearity, contact angle,
      electroosmotic velocity, electroosmotic mobility, and electrokinetic potential in
      dependence on the surface treatment. The hybrid PDMS-glass microfluidic devices
      have further been tested as on-chip capillary electrophoresis systems for the
      separation of fluorescently labeled amino acids. It has been demonstrated that
      different methods of surface pretreatment of the PDMS-glass devices result in
      significantly different separation performance, with plate numbers varying from
      650 to 57 000 in dependence on the surface state and the nature of the amino
      acids. Electrophoretic separations of amino acids have been achieved within tens
      of seconds with detection limits of less than 2 microM (approximately 2 x 10(-16)
      to 2.5 x 10(-16) mol quantities at injection volumes of 110-120 pL). The detected
      amounts of fluorescein isothiocyante (FITC)-amino acids are at least ten times
      lower, since the amino acid:FITC ratio is 10:1 mol. The results demonstrate the
      perspective of such hybrid PDMS-glass microfluidic systems and the methods to
      modify their surfaces for on-chip separation methods for biomolecules.

PMID- 15719362
TI  - Detection of coexisting protein conformations in capillary zone electrophoresis
      subsequent to transient contact with sodium dodecyl sulfate solutions.
AB  - Non-native conformations of proteins were generated by temporary contact with
      aqueous solutions of sodium dodecyl sulfate (SDS) and separated from the native
      state with capillary zone electrophoresis (CZE) in alkaline borate buffer
      deficient of SDS. Nine proteins at concentrations of 2.0 or 3.0 mg.L(-1) were
      compared in terms of their susceptibility to SDS. For superoxide dismutase and
      ferritin the tendency of unfolding was modest with < 25% of the protein being
      transformed to the non-native state at 10 mmol.L(-1) SDS. Highest susceptibility
      was observed for albumin, myoglobin (Mb), and hemoglobin with > 75% in the non
      native state even at 2.0 mmol.L(-1) SDS. The influence of varying SDS
      concentrations on the conformational state of Mb was tested. Increasing the SDS
      concentration, circular dichroism revealed a reduction in alpha-helix, an
      increase in random coil, and an introduction of beta-sheet, which is absent in
      native structure. Modifications in the secondary structure were in agreement with
      distinct changes in the shape of the non-native Mb peak in CZE and make a gradual
      unfolding/refolding process with several coexisting molten globules instead of
      two-state transition of conformations most plausible for Mb. CZE was found to
      contribute to a further understanding of holo-Mb transformation towards a
      population of non-native conformations (i) by means of calculated peak area
      ratios of native to non-native states, which showed sigmoid transition, (ii) by
      detecting the release of the prosthetic heme group, and (iii) by changes in the
      effective electrophoretic mobility of the Mb-SDS peaks. Reconstituted holo-Mb
      forms differed in the Soret band around 410 nm, indicating diversity in the
      conformation of the heme pocket.

PMID- 15719363
TI  - Intra- and inter-allelic ordering of T cell receptor beta chain gene assembly.
AB  - Allelic exclusion at the TCRbeta locus mandates that gene assembly be regulated
      in a manner that permits feedback inhibition of further complete TCRbeta
      rearrangements upon pre-TCR expression. Here we show that assembly of TCRbeta
      chain genes from Vbeta, Dbeta and Jbeta gene segments is intra-allelically
      ordered, proceeding primarily through DJbeta, and not VDbeta, intermediates. This
      ensures that Vbeta to DJbeta rearrangement, which can be feedback inhibited, is
      the final step in the assembly process. A newly assembled VDJbeta rearrangement
      must be tested to determine if it is in-frame before Vbeta to DJbeta
      rearrangement is permitted on the alternate allele. This inter-allelic ordering
      may occur through a general inefficiency of Vbeta to DJbeta rearrangement and/or
      through static differences in accessibility of the two TCRbeta alleles. However,
      we find that within the regulatory context of allelic exclusion, Vbeta to DJbeta
      rearrangement proceeds to completion on both alleles. Furthermore, all possible
      VDJbeta rearrangements are not completed on one allele before Vbeta to DJbeta
      rearrangement is initiated on the alternate allele. Together, these data support
      a dynamic model of inter-allelic accessibility that permits the ordered and
      efficient assembly of complete variable region genes on both TCRbeta alleles
      during T cell development.

PMID- 15719364
TI  - Rapid in vivo analysis of mutant forms of the LAT adaptor using Pax5-Lat double
      deficient pro-B cells.
AB  - Following injection into recombinase-activating gene-deficient (Rag1(-/-)) mice,
      pro-B cells lacking the Pax5 transcription factor (Pax5(-/-)) develop into most
      major hematopoietic lineages, with the notable exception of B cells. We assessed
      whether Pax5(-/-) pro-B cells that were also rendered deficient for the linker
      for activation of T cells (LAT), an adaptor essential for T cell receptor
      signaling, can be used for the rapid in vivo analysis of mutant forms of LAT. We
      showed that Pax5(-/-) Lat(-/-) pro-B cell lines can be infected with recombinant
      retroviruses expressing a LAT cDNA and sorted for the expression of LAT. When
      injected into Rag1(-/-) mice, they restore normal intrathymic T cell development
      and give rise to functional peripheral T cells. Considering that the handling of
      Pax5(-/-) pro-B cell lines is easier than that of bone marrow hematopoietic
      precursors, we used them for the rapid functional analysis of a novel Lat allelic
      series. When compared to knock-in and transgenic approaches, a major advantage of
      our Pax5(-/-) pro-B cell-based experimental approach consists in the production
      of mice bearing a given mutation within 2-3 months. Therefore, it constitutes a
      powerful first-line screen for mutations worth fastidious knock-in approaches.

PMID- 15719366
TI  - Direct effects of T-bet and MHC class I expression, but not STAT1, on peripheral
      NK cell maturation.
AB  - The homeostatic maturation of NK cells is severely impaired in mice lacking the
      transcription factor T-bet, and the expression of the NK cell maturation marker
      killer cell lectin-like receptor G1 (KLRG1) has been shown to be dependent on MHC
      class I molecules. Interferon (IFN)-gamma signaling via the signal transducer and
      activator of transcription (STAT)1 is vital for T-bet and MHC class I induction.
      Here we investigated the relationship between STAT1, T-bet, and MHC class I
      molecules with regard to the phenotypic maturation of peripheral NK cells. We
      demonstrate that, to varying degrees, the maturation status of peripheral NK
      cells is impaired in naive mice with deficiencies in STAT1, T-bet, or MHC class I
      molecules. We find that in naive animals, the expression of wild-type levels of
      MHC class I molecules in trans is sufficient to restore the maturation profiles
      of STAT1(-/-) NK cells in vivo. In contrast, expression of T-bet is required in
      cis for normal NK cell maturation to occur. Additionally, we demonstrate that the
      activation-induced maturation of NK cells during the course of murine
      cytomegalovirus (MCMV) infection does not require expression of MHC class I
      molecules or STAT1 but is severely delayed in the absence of T-bet.

PMID- 15719365
TI  - T cell homeostasis requires G protein-coupled receptor-mediated access to trophic
      signals that promote growth and inhibit chemotaxis.
AB  - Signals that regulate T cell homeostasis are not fully understood. G protein
      coupled receptors (GPCR), such as the chemokine receptors, may affect homeostasis
      by direct signaling or by guiding T cell migration to distinct location
      restricted signals. Here, we show that blockade of Galphai-associated GPCR
      signaling by treatment with pertussis toxin led to T cell atrophy and shortened
      life-span in T cell-replete hosts and prevented T cell homeostatic growth and
      proliferation in T cell-deficient hosts. In vitro, however, neither GPCR
      inhibition nor chemokine stimulation affected T cell atrophy, survival, or
      proliferation. These findings suggest that GPCR signals are not trophic stimuli,
      but instead may be required for migration to distinct trophic signals, such as IL
      7 or self-peptide/MHC. Surprisingly, while chemokines did not affect atrophy,
      atrophic T cells displayed increased chemokine-induced chemotaxis that was
      prevented by IL-7 and submitogenic anti-CD3 antibody treatment. This increase in
      migration was associated with increased levels of GTP-bound Rac and the ability
      to remodel actin. These data suggest a novel mechanism of T cell homeostasis
      wherein GPCR may promote T cell migration to distinct location-restricted
      homeostatic trophic cues for T cell survival and growth. Homeostatic trophic
      signals, in turn, may suppress chemokine sensitivity and cytoskeletal remodeling,
      to inhibit further migration.

PMID- 15719367
TI  - Thymic cortical epithelium induces self tolerance.
AB  - Because of its role in positive selection, the ability of cortical epithelium to
      induce tolerance is controversial. On the one hand, experiments with transplanted
      thymuses showed that the recipients were functionally tolerant of all the
      antigens expressed by the cells of those thymuses, including cells of the
      cortical epithelium. On the other, the keratin 14 (K14) transgenic mouse strain,
      which expresses MHC class II on cortical epithelium under the control of the K14
      promoter, does not seem to be tolerant of the transgenic MHC molecule. Here we
      tested whether the lack of tolerance in the K14 mouse might be more apparent than
      real. We found that K14 mice are indeed completely tolerant of K14 cortical
      thymic epithelium, whereas they remain reactive to tissues that express the same
      MHC allele under normal genetic control. These results establish the ability of
      cortical epithelium to induce central tolerance, and impinge on several of the
      models concerning positive selection of newly developing T cells.

PMID- 15719368
TI  - CD4+ T cell immunity against the human papillomavirus-18 E6 transforming protein
      in healthy donors: identification of promiscuous naturally processed epitopes.
AB  - Infection by 'high-risk' human papillomaviruses (HPV) is associated with the
      development of neoplastic lesions. HPV-18 is responsible for a very aggressive
      form of cancer and poor survival. As for other HPV types, immune surveillance has
      probably a role in the control of the infection. However, very little is known on
      HPV-18 immunogenicity. CD4(+) T cells from 16 healthy donors were tested ex vivo
      for reactivity to synthetic peptides corresponding to 3 sequences on the HPV-18
      E6 transforming protein predicted by bioinformatics as promiscuous HLA-DR
      ligands, and to the recombinant E6 protein. We found 3 donors with CD4(+) T cells
      that specifically proliferated in the presence of HPV-18 E6 antigens and produced
      IFN-gamma in the presence of the E6 protein. We then propagated CD4(+) T cell
      lines and clones from the responsive subjects to better characterize the
      recognized sequences. We show that E6(52-66) and E6(97-111) are indeed
      promiscuous and, most importantly, they contain naturally processed epitopes.
      Collectively, our data indicate that healthy donors may develop spontaneous CD4
      immunity against HPV-18 E6 epitopes, thus strongly suggesting the potential for
      this protein to elicit in the host a natural productive immune response.

PMID- 15719370
TI  - Reduced 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity response in
      IL-15 receptor alpha-deficient mice correlates with diminished CCL5/RANTES and
      CXCL10/IP-10 expression.
AB  - Using a model of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity
      (CHS) we found that, as compared with wild-type mice, IL-15 receptor alpha chain
      (IL-15Ralpha)-deficient mice showed significantly less ear swelling. This
      decreased response was associated with diminished expression of CCL5/RANTES and
      CXCL10/IP-10, chemokines critical for effector cell recruitment, in the inflamed
      tissue. We determined that both the number of CD8(+) T cells infiltrating the
      affected skin and the production of CCL5/RANTES by antigen-stimulated CD8(+) T
      cells were decreased in IL-15Ralpha(-/-) mice. The lower levels of CXCL10/IP-10
      suggested that the IL-15Ralpha(-/-) mice had reduced production of IFN-gamma, the
      primary inducer of CXCL10/IP-10, which was in fact the case. However, by contrast
      with CCL5/RANTES, the diminished levels of IFN-gamma were likely due to the
      decreased number of skin-infiltrating CD8(+) T cells, since IFN-gamma production
      by antigen-stimulated CD8(+) T cells was comparable between wild-type and IL
      15Ralpha(-/-) mice. Our data suggest a positive, pro-inflammatory feedback loop
      involving CCL5/RANTES, IFN-gamma and CXCL10/IP-10 that underlies the CHS reaction
      and that is disrupted, likely primarily by a defect in CCL5/RANTES production, in
      mice lacking IL-15Ralpha, resulting in impaired leukocyte recruitment and
      inflammation. Moreover, it is particularly noteworthy that the defect in
      CCL5/RANTES expression in CD8(+) T cells is intrinsic to the absence of IL
      15Ralpha, indicating that IL-15Ralpha is critical for CCL5/RANTES expression in
      CD8(+) T cells.

PMID- 15719369
TI  - In vitro and in vivo properties of a dimeric bispecific single-chain antibody IgG
      fusion protein for depletion of CCR2+ target cells in mice.
AB  - The chemokine receptor CCR2 is highly expressed on leukocytes in several
      inflammatory diseases of both mice and men. Apart from blockade of CCR2 to
      prevent chemokine-dependent cell migration, depletion of CCR2(+) cells might be a
      promising strategy for treatment of inflammatory diseases. We therefore designed
      a bispecific antibody construct with the ability to deplete CCR2(+) target cells
      in vitro and in vivo. The bispecific antibody construct consists of two single
      chain antibody variable fragments (scFv) - one recognizing murine CD3epsilon and
      the other recognizing murine CCR2 - joined by a short linker and fused to a
      modified hinge region and the C(H)2 and C(H)3 domains of murine IgG1 for
      dimerization. The protein was expressed in mammalian cells and purified via its C
      terminal histidine tail. In vitro this construct leads to efficient antigen
      specific and costimulation-independent activation of T cells and strong lysis of
      CCR2(+) target cells. In vivo the construct induces an almost complete depletion
      of CCR2(+)CD11b(+) monocytes from the peripheral blood and spleens of BALB/c mice
      within 24 h. This recombinant protein construct is a dimeric, bispecific antibody
      with markedly improved serum levels compared to conventional bispecific single
      chain antibodies and the ability to deplete CCR2(+)CD11b(+) monocytes in vivo.

PMID- 15719371
TI  - Pheochromocytoma and functional paraganglioma syndrome: no longer the 10% tumor.
AB  - Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors
      of the sympathetic nervous system, while head and neck paragangliomas are non
      secreting tumors of parasympathetic origin. Recent developments in clinical and
      molecular research on these tumor forms have significantly clarified their
      genetic backgrounds and challenged the view of "pheochromocytoma as the 10% rule
      tumor." Firstly, a larger proportion of these tumors are today discovered in
      normotensive patients during imaging carried out for other reasons than suspicion
      of pheochromocytoma. Secondly, although the differential diagnosis between
      malignant and benign tumors remains a challenge, the risk of malignancy well
      exceeds the classical 10% in patients with extra-adrenal disease, and/or carriers
      of germ-line SDHB mutations. Finally, up to a third of patients carry a germ-line
      mutation in a gene predisposing to pheochromocytoma and/or paraganglioma.
      Identification of a constitutional mutation in RET, VHL, SDHD, or SDHB has
      implications for clinical screening and follow-up for both the patient and for
      relatives at risk who can be identified by screening for the same mutation.
      Genetic testing in apparently sporadic cases is therefore regarded as beneficial,
      especially in patients diagnosed before 50 years of age, and in patients with
      bilateral, multifocal, malignant and/or extra-adrenal disease.

PMID- 15719372
TI  - Immunoregulatory effects of adenosine 5'-triphosphate on cytokine release from
      stimulated whole blood.
AB  - In vitro studies suggest that extracellular nucleotides and nucleosides may be
      important regulators of inflammatory and immune responses. Most studies with
      adenosine 5'-triphosphate (ATP) have been performed in cell lines, which are
      remote from the human situation. The purpose of the present study was to
      determine the effects of ATP on TNF-alpha, IL-6 and IL-10 release in stimulated
      whole blood. Blood samples were drawn from healthy volunteers and incubated with
      ATP and lipopolysaccharide (LPS) + phytohemagglutinin (PHA) for 24 h. Contrary to
      expectations, ATP at 100 microM and 300 microM induced a reduction in TNF-alpha
      secretion by 32+/-8% (mean +/- SEM) and 65+/-4%, respectively. Furthermore, these
      ATP concentrations induced an increase in IL-10 secretion by 48+/-5% and 62+/-7%
      in whole blood. The ATP analogue adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma
      S) and adenosine 5'-diphosphate (ADP) also inhibited TNF-alpha release, but only
      ADP showed a stimulatory effect on IL-10. Co-treatment with adenosine deaminase
      did not reverse the ATP effect on TNF-alpha and IL-10. These results show, for
      the first time, that ATP inhibits the inflammatory response in stimulated whole
      blood as indicated by inhibition of TNF-alpha and stimulation of IL-10 release
      and that this effect is predominantly mediated by ATP and not by adenosine.

PMID- 15719373
TI  - Management of midgut carcinoids.
AB  - Midgut carcinoids developing in the small intestine represent the most common
      cause of the carcinoid syndrome, with severe symptoms of flush, diarrhoea, and
      fibrotic valvular heart disease. The tumours may be histologically identified
      with specific chromogranin A or synaptophysine immunostainings, and by serotonin
      reactivity, which supports a midgut origin. Urinary 5-HIAA excretion and serum
      chromogranin A measurements are used as biochemical tumour markers for clinical
      diagnosis, and as important monitors of treatment effects and prognostic
      predictors. The midgut carcinoids have typically slow proliferation and extended
      disease course, and surgical treatment has become increasingly important for
      their management. Surgery should aim to remove primary tumours and mesenteric
      metastases, which may cause long-term abdominal complications, by typical
      fibrotic intestinal entrapment and small bowel ischaemia due to encasement of
      mesenteric vessels. Attempts should also be made to surgically remove or ablate
      liver metastases, since this may significantly contribute to palliation of the
      carcinoid syndrome. In patients with this syndrome surgery is combined with
      continuous biotherapy with long-acting somatostatin analogues and interferon,
      which may alleviate symptoms and cause stable disease with slow progression.
      Favourable survival and life-quality can be expected with this treatment also in
      patients with advanced midgut carcinoids.

PMID- 15719374
TI  - From incidentaloma to adrenocortical carcinoma: the surgical management of
      adrenal tumors.
AB  - In this article we review the management of benign and malignant adrenal tumors,
      with an emphasis on oncologic concerns. Concise, logical guidelines for the
      diagnosis and operative treatment of incidentalomas, aldosteronomas, adrenal
      Cushing syndrome, virilizing and feminizing adrenal tumors, isolated adrenal
      metastases, and adrenocortical carcinoma are provided. We also discuss the choice
      of optimal surgical approach for performing adrenalectomy (laparoscopic, open,
      hand-assist).

PMID- 15719375
TI  - Parathyroid carcinoma.
AB  - Parathyroid carcinoma is an uncommon malignancy. It accounts for less than 1% of
      cases of primary hyperparathyroidism (HPT). It is manifested by severe
      hypercalcemia and up to 50% of patients will have concomitant kidney or bone
      disease. The etiology of parathyroid carcinoma is unknown, however, the recently
      discovered HRPT2 gene, a tumor suppressor gene encoding for the protein
      parafibromin, has been implicated in the pathogenesis. Identification of
      inactivating germ-line mutations in HRPT2 has significant implications for
      diagnosis and management. This article summarizes the genetic aspects of
      parathyroid carcinoma, reviews its clinical manifestations, and outlines the
      principles of surgical therapy, the indications for adjuvant therapy, and the use
      of bisphosphonate and calcimimetic agents for management of hypercalcemia.

PMID- 15719376
TI  - Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal
      tract.
AB  - Factors that determine the clinical course and outcome of patients with
      gastrointestinal (GI) carcinoid tumors are complex and multifaceted. These
      include the site of origin within the GI tract, the size of the primary tumor,
      and the anatomical extent of disease, whether localized, regional, or metastatic
      to distant sites. The new World Health Organization (WHO) histological
      classification of endocrine tumors, including carcinoids, represents a
      significant advance in terms of providing a consistent framework for
      histopathological interpretation that should facilitate multicenter research on
      treatment outcomes. Histochemical indicators of a poorer prognosis are the degree
      of expression of the proliferation protein Ki-67 and the p53 tumor suppressor
      protein. Adverse clinical indicators are the malignant carcinoid syndrome,
      carcinoid heart disease, and high concentrations of the tumor markers, urinary 5
      HIAA and plasma chromogranin A.

PMID- 15719377
TI  - Follicular thyroid lesions, elements that affect both diagnosis and prognosis.
AB  - The precise diagnosis of follicular thyroid lesions is frequently debated because
      of the subjective nature of capsular invasion as well as both the histological
      and cytological characteristics. Furthermore, several different prognostic
      indices have been devised to examine prognosis associated with thyroid cancer.
      Herein, we describe how these confounding elements can affect the ability to
      accurately predict prognosis for patients with follicular thyroid lesions.

PMID- 15719378
TI  - Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes.
AB  - Medullary thyroid carcinoma (MTC) is a rare malignancy with several distinctive
      features that distinguish its management from other thyroid cancers. First, MTC
      may be sporadic (75% of cases), or may occur as a manifestation of the hereditary
      syndrome Multiple Endocrine Neoplasia type 2 (MEN 2) (25% of cases).
      Additionally, while MTC is more difficult to cure than differentiated thyroid
      cancer and has higher rates of recurrence and mortality, it is usually a slow
      growing tumor compared with other malignancies. Finally, unlike differentiated
      thyroid cancer, there is no known effective systemic therapy for MTC. MTC cells
      do not concentrate radioactive iodine, and MTC does not respond well to external
      beam radiation or conventional cytotoxic chemotherapy. These distinguishing
      features should be considered in planning surgical management of MTC.

PMID- 15719379
TI  - Surgical treatment of non-functioning pancreatic islet cell tumors.
AB  - Pancreatic endocrine tumors (PETs) are rare neoplasms originating from the amine
      precursor uptake and decarboxylation (APUD) stem cells. Although the majority of
      PETs are sporadic, they frequently occur in familial syndromes. PETs may cause a
      variety of functional syndromes or symptoms of local progression if they are non
      functional. General neuroendocrine tumor markers are highly sensitive in the
      diagnostic assessment of a PET. Imaging studies for tumor localization and
      staging include computer tomography (CT) scan, magnetic resonance imaging (MRI),
      In(111)-octreotide scan, MIBG, and endoscopic ultrasonography (EUS). Treatment of
      PETs often requires a multi-modality approach; however, surgical resection
      remains the only curative therapy for localized (non-metastatic) disease.
      Treatment of metastatic disease includes biologic agents, cytotoxic chemotherapy,
      and liver-directed therapies.

PMID- 15719380
TI  - Kindred spirits of the endocrines: the training of the future endocrine surgeons.
AB  - The growth of knowledge and complexity now seen in General Surgery, has led to
      the sub-specialization of the discipline. Although it is considered by some to
      have led to the fragmentation of General Surgery and the erosion of the specialty
      as we know it today, others would argue that it has and will continue to lead to
      a stronger division and a higher standard of care. Most would argue that a higher
      standard of care in focus areas stimulates research and research, in turn,
      improves the quality of education and training. Ultimately, improved education
      and training leads to better patient care. Organ-specific specialization such as
      orthopedics and urology evolved from General Surgery and demonstrates this
      principle. Further sub-specialization is likely inevitable, if the discipline of
      General Surgery is to remain a desired specialty. Endocrine surgery has evolved
      into a sub-specialty of General Surgery, and over the last few decades has
      matured as a discipline. With this maturation comes the responsibility of
      defining the standard of care to be provided by surgeons involved in endocrine
      surgery. To achieve this goal, endocrine surgical associations and societies must
      set the standard of training both at the residency and postgraduate level. Where
      we are as a sub-specialty, where we came from, and what it will take to meet this
      goal are discussed.

PMID- 15719381
TI  - The surgeon's armamentarium to the surgical treatment of primary
      hyperparathyroidism.
AB  - Parathyroidectomy cures the vast majority of patients with primary
      hyperparathyroidism (HPT). While bilateral neck exploration has been the mainstay
      of therapy, recent advances in technology have revolutionized the field making a
      focused approach to parathyroidectomy a reality. The development of accurate pre
      operative localization with sestamibi scanning, effective unilateral, endoscopic
      and video-assisted techniques, and rapid intra-operative parathyroid hormone
      (PTH) testing have made it possible to cure patients with the least amount of
      surgical dissection possible. In this paper, we will explore the role of focused
      parathyroidectomy in the surgical treatment of primary HPT.

PMID- 15719382
TI  - Multiple endocrine neoplasia type 1.
AB  - Multiple endocrine neoplasia-1 (MEN-1) is an autosomal dominant inherited
      syndrome that occurs due to inactivating mutations of the MEN1 gene locus, coding
      for a tumor-suppressor protein, menin. The components of MEN-1 are
      hyperparathyroidism due to multiple parathyroid adenomas, pancreatic
      neuroendocrine tumors, and pituitary adenomas, in addition to some less common
      neoplastic manifestations. Care of people with MEN-1 requires knowledge of the
      problems that may arise, and the best approaches to detect and care for the
      manifestations of this incurable, but manageable, disease.

PMID- 15719383
TI  - Endocrine surgery: Our current understanding of the treatment and the
      controversies within this diverse group of tumors.

PMID- 15719384
TI  - Role of 131I in the treatment of well differentiated thyroid cancer.
AB  - (131)I is an integral component in postsurgical management of well-differentiated
      thyroid cancer (WDTC), which includes papillary and follicular types. (131)I is
      used postsurgically to either destroy remaining thyroid tissue (thyroid ablation)
      or to treat recurrence and metastases (radioiodine therapy). (131)I is no longer
      a routine diagnostic modality, but it is widely used for remnant ablation after
      thyroidectomy for WDTC > 1 cm, under conditions of thyroxine withdrawal. It is
      generally-though not unanimously-accepted that postsurgical radioiodine is the
      most powerful method by which to lengthen disease-free survival. (131)I cannot be
      used if the residual thyroid remnant is large; many surgeons therefore perform
      near-total or total thyroidectomy for all WDTC > 1 cm. Since 1997, radioiodine
      treatment has been performed in outpatient settings, where side effects are
      common, but mild and transient. Secondary screening is by physical exam,
      thyroglobulin measurements, and (131)I diagnostic whole-body scans. This is
      performed under conditions of thyrotropin stimulation, which is accomplished
      either by thyroxine withdrawal or administration of recombinant human
      thyrotropin. While most cancers are well treated with radioiodine, some advanced
      cancers may no longer take up radioiodine, rendering them resistant to treatment.
      For these cancers, redifferentiation therapy and molecular target-specific
      medicines hold future promise for improved treatment.

PMID- 15719385
TI  - Can a leukocyte depletion filter (LDF) reduce the risk of reintroduction of
      hepatocellular carcinoma cells?
AB  - During liver transplantation for hepatocellular carcinoma (HCC) patients, HCC
      could theoretically be introduced into the systemic circulation when salvaged
      blood is used with an autotransfusion device. Several reports have shown that
      some types of leukocyte depletion filters (LDFs) could completely reduce the risk
      for reintroducing some types of tumor cells. In this study, we tested the ability
      of the LDF (RCEZ1T, Pall Biomedical Co, NY, USA) to reduce the risk for
      reintroducing HCC cells in vitro by using a very sensitive detection method. We
      divided the test group into 6 groups: group I was 10 cells, group II was 20
      cells, group III was 2 x 10(3) cells, group IV was 2 x 10(5) cells, group V was 2
      x 10(6) cells, and group VI was 2 x 10(7) cells. The counted cells in 200 mL
      saline were passed through the RCEZ1T using the force of gravity. To identify the
      presence of cells, the pellet was resuspended, and polymerase chain reaction
      (PCR) was performed. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a
      housekeeping gene, was used as a primer. In groups I and II, the HCC cells were
      completely filtered in all experiments. However, in groups III, IV, and V, the
      HCC cells were not completely filtered in a few of the repeated experiments, with
      the unfiltered rate of tumor cells being between 8% and 20%. In group VI, the HCC
      cells were not completely filtered in all the repeated experiments. In
      conclusion, the RCEZ1T filter markedly reduced the risk for reintroduction of HCC
      cells. However, at high HCC cell load the filter cannot completely remove all the
      tumor cells. Further studies are required to assess the impact in clinical
      settings.

PMID- 15719387
TI  - Herpes zoster infection after liver transplantation: a case-control study.
AB  - Prior case series have suggested that herpes zoster (HZ) after orthotopic liver
      transplantation (OLT) may lead to serious complications due to visceral
      involvement. We sought to determine the incidence, risk factors, and long term
      outcomes of HZ after OLT. Clinical data from September 1993 to April 2004 were
      collected on all cases of HZ after OLT, and at the same post-OLT time points in
      age, gender, and transplant-year-matched HZ-negative controls. Risk factors for
      HZ infection and long-term outcomes were compared between cases and controls. A
      total of 29 patients developed HZ at a median of 4.9 years (range .5-12.9) after
      OLT. All HZ infections except 1 were localized to a single dermatome. Only 8
      (28%) were hospitalized and 16 (55%) were treated with oral antivirals alone. No
      patients developed visceral involvement or died of HZ infection. No risk factors
      for HZ infection were identified on multivariate analysis. Of the long-term
      outcomes, the estimated 10-year survival was lower (P = .05) for cases than
      controls. The lower survival in HZ cases was not directly attributable to HZ
      infection. In conclusion, this study is the largest series on HZ after OLT. HZ is
      neither a common nor a serious infection after OLT and can be managed with
      antiviral therapy with a low likelihood of visceral dissemination.

PMID- 15719386
TI  - Addition of serum sodium into the MELD score predicts waiting list mortality
      better than MELD alone.
AB  - In this study, we investigated the prognostic value of serum sodium and
      hyponatremia (< or =130 mEq/L) in 262 cirrhotic patients consecutively listed, 19
      of which died (7%), 175 survived (67%), and 68 underwent liver transplantation
      (26%) during 3 months of follow-up. Hyponatremia was present in 63% of patients
      who died, compared to 13% of those who survived (P < .001), whereas the
      proportion with elevated creatinine (> or =1.4 mg/dL) was low and similar in both
      groups (10.5 vs. 3%). Prevalence of hyponatremia was higher than that of elevated
      serum creatinine across all model for end-stage liver disease (MELD) categories.
      Using logistic regression, hyponatremia and serum sodium were significant
      predictors of mortality with concordance statistics (c-statistics) .753 for
      hyponatremia, .784 for sodium, .894 for MELD, .905 for MELD plus hyponatremia (P
      = .006 vs. MELD alone), and .908 for MELD plus serum sodium (P = .026 vs. MELD
      alone). Risk of death across all MELD scores was higher for patients with
      hyponatremia than without hyponatremia. Cox regression considering data within 6
      months of follow-up yielded qualitatively similar results, with hyponatremia
      being a significant predictor of greater mortality risk with an odds ratio of
      2.65 (P = .015). Each increase of 1 mEq/L of serum sodium level was associated
      with a decreased odds ratio of .95 (P = .048). Our results indicate that
      hyponatremia appears to be an earlier and more sensitive marker than serum
      creatinine to detect renal impairment and / or circulatory dysfunction in
      patients with advanced cirrhosis. In conclusion, addition of serum sodium to MELD
      identified a subgroup of patients with poor outcome in a more efficient way than
      MELD alone and significantly increased the efficacy of the score to predict
      waitlist mortality.

PMID- 15719388
TI  - The development of food allergy after liver transplantation.
AB  - The acquisition of new food allergy after orthotopic liver transplantation is now
      a well described phenomenon, mainly reported in children. The etiology of this
      phenomenon is at present unclear, but has been ascribed by some to tacrolimus
      treatment. Here we report a case of liver transplant acquired food allergy
      (LTAFA) in a child who received a split liver graft. The case is remarkable for
      the absence of new food allergy in the adult recipient of the same graft. This
      suggests that host-specific factors play an important role in the development of
      food allergy after liver transplantation, and emphasizes the predisposition that
      children have toward this phenomenon. Possible mechanisms underlying the
      development of food allergy after liver transplantation are discussed. In
      conclusion, tacrolimus treatment alone cannot account for LTAFA. Host factors
      such as the maturity of immune regulatory mechanisms are likely to play a
      critical role in the development of new food allergy after a liver transplant.

PMID- 15719389
TI  - Reconstruction of the middle hepatic vein tributary in a right lateral sector
      graft.
AB  - A right lateral sector graft (RLSG) was devised to overcome graft-size disparity
      in living donor liver transplantation (LDLT). When the RLSG has a middle hepatic
      vein (MHV) tributary, which drains a significant part of segment VI, the MHV
      tributary (V6) should be reconstructed to avoid congestion of the RLSG. In the
      donor operation, congestive area of segment VI was identified by 5 minutes of
      simultaneous clamping of V6 and the hepatic artery to the right lateral sector.
      An RLSG was harvested, preserving the V6 orifice. After plastic surgery of
      outflow veins including V6 using venous grafts, the RLSG was implanted into the
      recipient. In 19 patients who received RLSG in our institution, 2 RLSGs required
      V6 reconstruction. The postoperative courses of these two recipients and donors
      were uneventful. In conclusion, the present technique might be useful to avoid
      complications due to congestion and poor function of the relevant graft area and
      might help to expand the indications for RLSG.

PMID- 15719390
TI  - Safety of donor right hepatectomy without abdominal drainage: a prospective
      evaluation in 100 consecutive liver donors.
AB  - Although the role of routine abdominal drainage after liver resection for tumors
      has been questioned, abdominal drainage after donor right hepatectomy for live
      donor liver transplantation (LDLT) has been a routine practice in most transplant
      centers. The present study aimed to evaluate the safety of the procedure without
      abdominal drainage. A prospective study was performed on 100 consecutive liver
      donors who underwent right hepatectomy for LDLT from July 2000 to September 2003.
      Biliary anatomy was carefully studied with intraoperative cholangiography using
      fluoroscopy. The middle hepatic vein was included in the graft in all except 1
      patient. Parenchymal transection was performed using an ultrasonic dissector. The
      right hepatic duct was transected at the hilum and the stump was closed with 6-O
      polydioxanone continuous suture. Absence of bile leakage was confirmed with
      methylene blue solution instilled through the cystic duct stump. The abdomen was
      closed after careful hemostasis without drainage in all donors. The median age of
      the donors was 36 years (range 18-56 years). Median operative blood loss and
      operating time were 350 mL (range 42-1,400 mL) and 7.5 hours (range 5.2-10.7
      hours), respectively. None of the donors required any blood or blood product
      transfusion. There was no operative mortality. The median postoperative hospital
      stay was 8 days (range 5-30 days). Postoperative morbidity occurred in 19
      patients (19%), most of which were minor complications. No donor experienced bile
      leakage, intraabdominal bleeding, or collection. None required surgical,
      radiologic, or endoscopic intervention for postoperative complications, except
      for 1 donor who developed late biliary stricture that required endoscopic
      dilatation. All donors were well with a median follow-up of 32 months (range 11
      50 months). In conclusion, with detailed study of the biliary anatomy and
      meticulous surgical technique, donor right hepatectomy can be safely performed
      without abdominal drainage. Abdominal drainage is not a mandatory procedure after
      donor hepatectomy in LDLT.

PMID- 15719391
TI  - Toxicity and outcome analysis of patients with recurrent head and neck cancer
      treated with hyperfractionated split-course reirradiation and concurrent
      cisplatin and paclitaxel chemotherapy from two prospective phase I and II
      studies.
AB  - BACKGROUND: Patients with local recurrences or new head and neck primary tumors
      in previously irradiated tissues have few options for salvage treatment. One
      option for select patients is to undergo reirradiation with concurrent
      chemotherapy. The purpose of this study is to report the initial clinical results
      of the Fox Chase phase I and II prospective reirradiation and chemotherapy
      studies. METHODS: Between July 1996 and January 2002, 38 patients with locally
      recurrent unresectable squamous cell carcinoma of the head and neck were treated
      with concurrent chemotherapy and reirradiation on two prospective trials. All
      patients had received prior radiation therapy to the head and neck region (median
      dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with
      hyperfractionated external beam radiation therapy to the site of recurrence.
      RESULTS: The median follow-up was 10 months. The median survival was 12.4 months,
      with actuarial rates of overall survival of 50% and 35% at 1 and 2 years,
      respectively. During follow-up, 63% of patients experienced local progression of
      disease, all in the irradiated field. Actuarial progression-free survival at 1
      year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4
      toxicity included neutropenia, nausea, emesis, and mucositis. CONCLUSIONS:
      Hyperfractionated split-course reirradiation and concurrent cisplatin and
      paclitaxel chemotherapy demonstrates durable locoregional control in select
      patients, although late toxicity may occasionally be significant. Only sites of
      disease recurrence need to be covered in the reirradiation fields.

PMID- 15719393
TI  - Evidence-based evolution of the MELD/PELD liver allocation policy.

PMID- 15719392
TI  - Suppression of accelerated tumor growth in surgical wounds by celecoxib and
      indomethacin.
AB  - BACKGROUND: Tumor growth is accelerated in surgical wounds. However, few
      experiments seeking to prevent such accelerated tumor growth have been performed.
      METHODS: We created surgical wounds in three syngeneic mice for the implantation
      of three murine cancer cell lines, SCC VII, CT-26, and B16F10. The tumor growth
      in the wound group was compared with that in non-wound-control mice. Celecoxib or
      indomethacin was administered to the mice that had tumor implanted into the
      surgical wound to observe the tumor-suppressive effect. RESULTS: The surgical
      wounds promoted tumor growth with different degrees, depending on the type of
      tumor. Such an accelerated tumor growth did not seem to be affected by
      cyclooxygenase-2 expression of tumors per se, but its mechanism needs to be
      explained by further studies. Celecoxib and indomethacin had a significant
      inhibitory effect on the tumor growth in the surgical wound. This suppressive
      effect is most obvious when celecoxib is administered daily from 1 day before
      surgical wounding and tumor implantation. CONCLUSION: Our results can justify
      that the preventive use of celecoxib in patients in whom local recurrence by
      tumor contamination is predicted.

PMID- 15719394
TI  - Cystatin C as a more sensitive indicator of diminished glomerular filtration
      rate.

PMID- 15719395
TI  - No association of GSK3beta gene (GSK3B) with Japanese schizophrenia.
AB  - Several lines of evidence indicate that glycogen synthase kinase-3beta (GSK3beta)
      is one of the candidates for schizophrenia-susceptibility factor. However, it has
      not been reported the association analysis between GSK3beta gene (GSK3B) and
      Japanese schizophrenia based on linkage disequilibrium (LD). We provide an
      association analysis using relatively large samples (381 schizophrenia, and 352
      controls) after determination of "tag single nucleotide polymorphisms (SNPs)." In
      this LD mapping, we selected and genotyped for eight polymorphisms (seven SNPs
      and one diallelic (CAA)(n) repeat), which covered the entire region of GSK3B, and
      determined two "tag SNPs." In the following association analysis using these two
      "tag SNPs," we could not find association with Japanese schizophrenia.
      Furthermore, we also include subgroup analysis considering age-at-onset and
      subtypes, neither could we find associations. Because our samples provided quite
      high power, these results indicate that GSK3B may not play a major role in
      Japanese schizophrenia.

PMID- 15719396
TI  - Association between BDNF val66 met genotype and episodic memory.
AB  - The val66 met polymorphism of brain derived neurotrophic factor (BDNF) has been
      associated with variability in episodic memory [Egan et al., 2003]. In an attempt
      to replicate this finding, we genotyped 206 individuals (92 affected with
      schizophrenia or a related disorder and 114 unaffected relatives) from the
      Maudsley Family Study for the BDNF val66 met polymorphism. We analyzed the effect
      of this polymorphism on episodic memory using the Wechsler Memory Scale, revised
      version (WMS-R) by regression analysis between the WMS delayed score of logical
      memory and genotype (corrected for age, sex, and IQ). We found the met66 allele
      conferred a lower score on the WMS delayed measure (R2 = 0.014 P = 0.09), which
      was not significant. When cases and unaffected relatives were analyzed
      separately, met66 was associated with a lower score on the WMS delayed measure in
      the relatives only (R2 = 0.077 P = 0.01), which is consistent with previous
      findings.

PMID- 15719397
TI  - The serotonin transporter gene as a QTL for ADHD.
AB  - Molecular studies of attention deficit hyperactivity disorder (ADHD) have
      identified susceptibility genes for the categorically diagnosed disorder using
      operational diagnostic criteria. Here, we take a QTL approach to mapping genes
      for ADHD using a composite continuous index of ADHD behavior in a large
      epidemiological sample. Previous studies of clinical ADHD suggest that two
      functional polymorphisms in the serotonin transporter gene (SLC6A4), one in the
      5'-regulatory region of the gene (5-HTTLPR) and the other a VNTR (5-HTTVNTR) in
      the second intron, as well as a single nucleotide polymorphism in the 3'
      untranslated region (3'-UTR SNP), may be associated with the disorder. Here, we
      investigate these polymorphisms as well as an additional ten SNPs spread across
      the gene. We found significant association with the long (L) allele of the 5
      HTTLPR; P = 0.019, but neither the 5-HTTVNTR nor the 3'-UTR SNP were
      significantly associated. Significant associations (P < 0.05) were found for a
      further 5 the 10 other markers tested. We found evidence for two haplotype blocks
      spanning the region. We found strong evidence for association with the first
      haplotype block (comprised of four markers), with the significance of a combined
      primary and secondary test of association reaching an empirical P value = 0.0054
      for the global test and an empirical P value = 0.00081 for the largest local
      test. Thus, we show here that SLC6A4, which has a major influence on brain
      serotonin availability, may be a QTL for ADHD.

PMID- 15719398
TI  - DNA pooling analysis of 21 norepinephrine transporter gene SNPs with attention
      deficit hyperactivity disorder: no evidence for association.
AB  - The norepinephrine system is known to play a role in attentional and cognitive
      energetic mechanisms and is thought to be important in attention deficit
      hyperactivity disorder (ADHD). Stimulant medications are known to alter the
      activity of norepinephrine as well as dopamine in the synapse and the highly
      selective norepinephrine reuptake inhibitor, atomoxetine, is an effective
      treatment for ADHD symptoms. This study set out to investigate whether common
      polymorphisms within the norepinephrine transporter gene (NET1) are associated
      with DSM-IV ADHD combined subtype, using a sample that has previously shown
      association with genes that affect the synaptic release and uptake of
      neurotransmitters; DAT1 and SNAP-25. We identified 21 single nucleotide
      polymorphisms (SNPs) from publicly available databases that had minor allele
      frequencies > or =5% and span the NET1 genomic region, including those analyzed
      in previous studies of ADHD. DNA pooling was used to screen for associations
      using two case pools (n = 180 cases) and four control pools (n = 334 controls).
      We identified three SNPs that showed suggestive evidence for association using
      either case-control or within family tests of association, however, none of these
      were significant after adjustment for the number of markers analyzed. We conclude
      that none of the markers show significant evidence of association with ADHD
      although we cannot rule out small genetic effects.

PMID- 15719399
TI  - Erythropoietin is approved for the treatment of anemia associated with renal
      failure, chemotherapy, preoperative anemia, and human immunodeficiency virus
      disease.

PMID- 15719401
TI  - Prope tolerance with alemtuzumab.

PMID- 15719402
TI  - Hepatic venous outflow reconstruction in right live donor liver transplantation.
AB  - The increasing experience with live donor liver transplantation has allowed for
      the identification of potential morbidities associated with technical
      considerations. Technical graft failure can be associated with both inflow and
      outflow vascular compromise. Although the latter has not always been given the
      relevance of the former, evidence pointing to its pivotal role continues to
      mount. We believe that impaired venous outflow was a cause of previously
      unexplained graft failures during our initial experience. Based on this
      observation, we developed a technique to prevent the "choking" of the graft at
      the outflow anastomosis with the inferior vena cava (IVC). The enhanced outflow
      via a cloaca maximum is achieved by reconstructing the graft vessels with
      preserved veins or arteries (usually iliac vessels are used) from a blood-group
      identical or blood-group-compatible deceased organ donor. Alternatively, hepatic
      vein or portal vein obtained from the resected native liver can be used. The
      reconstructed common outflow is anastomosed to a triangular opening of the IVC.
      Such enhanced outflow provides optimal venous drainage, especially during the
      early phase of growth of the graft.

PMID- 15719403
TI  - MARS treatment for a patient presenting with acquired hepatic glutamine
      synthetase deficiency after orthotopic liver transplantation.
AB  - We report a 48-year-old man presenting with refractory hyperammonemia after
      orthotopic liver transplantation. On investigation he was found to have acquired
      hepatic glutamine synthetase deficiency, a rare condition that occurs after organ
      transplantations. The patient was started on continuous venovenous hemofiltration
      treatment, but the hyperammonemia did not respond. The patient was then subjected
      to molecular adsorption recirculation system (MARS) therapy and the ammonia level
      gradually improved with successive treatments. In conclusion, the response was
      unlikely due to the hemofiltration component of MARS alone but more probably due
      to the removal of putative albumin-bound toxin by the adsorption circuit that had
      ameliorated the internal milieu of the graft and reversed the enzyme deficiency.

PMID- 15719404
TI  - New hepatic vein reconstruction in left liver graft.
AB  - The incidence of hepatic venous stenosis is higher in partial liver
      transplantation. New methods for hepatic venous reconstruction in left liver
      transplantation, which secure wide anastomosis, were devised and are reported
      here. In the graft, the right side of the middle hepatic vein or the left side of
      the left hepatic vein was cut longitudinally and a rectangular-shaped vein patch
      was attached for venoplasty. In the recipient, after the left and middle hepatic
      veins were joined, the right side of the middle hepatic vein was cut toward the
      closed right hepatic vein, making a horizontal cavotomy for anastomosis. Of 92
      patients who underwent conventional hepatic vein reconstruction, 3 were
      complicated by hepatic venous stenosis (median follow-up 43 months). By contrast,
      there were no hepatic vein complications in the 20 patients who underwent the new
      technique (7 months). The current method appears to be technically feasible for
      outflow reconstruction in left liver graft transplantation.

PMID- 15719405
TI  - Cystatin C, an easy and reliable marker for assessment of renal dysfunction in
      children with liver disease and after liver transplantation.
AB  - Renal dysfunction of variable severity is being increasingly recognized as a
      major complication of calcineurin inhibitors (CI), in some patients even
      necessitating renal transplantation. Close and effective monitoring of the renal
      function is indicated. Current methods for this monitoring are calculation of the
      glomerular filtration rate (GFR) based on creatinine or exogenous substances like
      51Cr-EDTA. The first method is unreliable in children and the second is expensive
      and cumbersome. Cystatin C has been shown to be an accurate marker of glomerular
      filtration but has not been evaluated in a large cohort of pediatric patients
      before and after liver transplantation (LT). We evaluated the accuracy of
      cystatin C in 62 children (30 male) with LT, who had their 51Cr-EDTA measured on
      40 occasions prior to LT and on 47 occasions after LT. The reciprocal of cystatin
      C correlated better with 51Cr-EDTA GFR (r = .78) than the reciprocal of
      creatinine (r = .40). Diagnostic accuracy in the identification of reduced GFR
      was assessed by ROC analysis. Cystatin C yielded the highest area under the ROC
      curve (AUC) in all groups assessed. From these data a cutoff level of cystatin C
      predicting 51Cr-EDTA GFR < 80 ml/min/1.73 m2 was calculated. A level of 1.06 mg/L
      was found to have a sensitivity of 91% and a specificity of 81%. Applying this
      cutoff level in our patient group would have avoided 51Cr-EDTA GFR estimation in
      43 of the 87 estimations. In conclusion, the use of this simple test could be
      recommended as screening of renal dysfunction in children with liver disease and
      after LT.

PMID- 15719406
TI  - Splitting of the middle hepatic vein in full-right full-left splitting of the
      liver.
AB  - Full-right/full-left splitting of the liver offers a chance to overcome the
      severe shortage of donor organs. During this procedure, the splitting surgeons
      are always faced with the question of how to share the middle hepatic vein (MHV),
      since this vein drains parts of both halves of the liver. Consequently, we
      developed a procedure that splits the MHV, thus creating an MHV on both grafts.
      In this short article, we report on this splitting technique and our first
      initial experience.

PMID- 15719407
TI  - Microchimerism after liver transplantation: absence of rejection without
      abrogation of anti-donor cytotoxic T-lymphocyte-mediated alloreactivity.
AB  - Microchimerism (MC) is defined by the persistence of <1% circulating donor cells
      resulting from cell migration from the graft; MC may play a role in the induction
      of unresponsiveness to allogeneic tissues, or may be merely the consequence of
      the graft's acceptance following immunosuppression. To analyze early MC (7
      patients) and late MC (12 patients) following a liver transplantation, we
      designed a sensitive and semiquantitative nested polymerase chain reaction (PCR)
      protocol based on the detection of incompatible human leukocyte antigen (HLA)
      DRB1 donor alleles. MC was measured in multiple PCR samples and expressed as
      percent positive PCRs / time point. The detection level was 1 donor cell / 10(5)
      patient cells. All patients had detectable early MC, ranging from 5 to 100%
      positive PCRs in the 1st 3 months after transplantation. The kinetic analysis
      demonstrated that MC decreased during the 1st year in 6 of 7 patients. All of the
      4 patients with the lowest MC had rejection episodes, vs. none among the 3
      patients with MC >50%. However, cytotoxic T-lymphocyte reactivity (CTL) against
      HLA class I donor antigens could be demonstrated 1 year posttransplant in 2
      patients with a high level of early MC. MC is a dynamic process, which is easily
      detectable <3 months after liver transplantation. In conclusion, a correlation
      between the level of early MC and the absence of rejection episodes was observed.
      However, high levels of early MC did not abrogate the persistence of an
      alloreactive response measured in vitro 1 year after transplantation, which
      suggests that MC did not lead to clonal deletion of donor-specific CTL.

PMID- 15719408
TI  - Short-term administration of (-)-epigallocatechin gallate reduces hepatic
      steatosis and protects against warm hepatic ischemia/reperfusion injury in
      steatotic mice.
AB  - Hepatic steatosis increases the extent of cellular injury incurred during
      ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major
      flavonoid component of green tea (camellia sinensis) is a potent antioxidant that
      inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG
      on hepatic steatosis and markers of cellular damage at baseline and after I/R
      injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via
      intraperitoneal (ip) injection for 2 days or oral consumption in the drinking
      water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion.
      After EGCG administration, total baseline hepatic fat content decreased from
      baseline. Palmitic acid and linoleic acid levels also were reduced substantially
      in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels
      decreased in all EGCG-treated animals compared with control animals after I/R.
      Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG
      administration. EGCG administration also increased resting hepatic energy stores
      as determined by an increase in cellular adenosine triphosphate (ATP) with a
      concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there
      was an increased level of glutathione (GSH) in the EGCG-treated mice compared
      with the vehicle-treated mice both at baseline and after I/R. In conclusion,
      taken together, this study demonstrates that treatment with ECGC by either oral
      or ip administration, significantly protects the liver after I/R, possibly by
      reducing hepatic fat content, increasing hepatic energy status, and functioning
      as an antioxidant.

PMID- 15719409
TI  - Immunosuppression in liver transplantation: beyond calcineurin inhibitors.
AB  - Although calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression
      in liver transplantation (LTX), their long-term toxicity significantly
      contributes to morbidity and mortality. The elucidation of mechanisms of
      alloimmunity and leukocyte migration have provided novel targets for
      immunosuppression development. The toxicities of these agents differ from that of
      the CNI and act additively or synergistically. CNI avoidance protocols in LTX
      have not been achieved routinely; however, pilot trials have begun to delineate
      the limitations and promises of such approaches. CNI-sparing protocols appear to
      be much more promising in balancing the early need for minimizing rejection while
      tapering doses and minimizing long-term toxicity.

PMID- 15719410
TI  - Improving the prediction of hepatocellular carcinoma in cirrhotic patients with
      an arterially-enhancing liver mass.
AB  - In the United States, cirrhotic patients with known or suspected hepatocellular
      carcinoma (HCC) are prioritized for liver transplantation. Noninvasive criteria
      for the diagnosis of HCC rely on arterial enhancement of a mass. The aim of this
      study was to determine whether clinical, laboratory, and / or radiologic data can
      improve the prediction of HCC in cirrhotic patients with an arterially-enhancing
      mass. Between May 2002 and June 2003, dynamic gadolinium-enhanced magnetic
      resonance imaging (MRI) of consecutive patients with liver cirrhosis and a solid
      mass were reviewed by 2 radiologists blinded to the clinical diagnosis. Clinical,
      laboratory, and radiologic data were recorded for all patients. A total of 94
      patients with cirrhosis and an arterially-enhancing liver mass were studied, 66
      (70%) of whom had HCC. Alpha-fetoprotein (AFP) >20 ng/mL (P = .029), tumor size
      >2 cm (P = .0018), and delayed hypointensity (P = .0001) were independent
      predictors of HCC. Delayed hypointensity of an arterially-enhancing mass had a
      sensitivity of 89% and a specificity of 96% for HCC. The presence of delayed
      hypointensity was the only independent predictor of HCC among patients with
      arterially-enhancing lesions <2 cm (odds ratio, 6.3; 95% confidence interval
      [CI], 1.8-13), with a sensitivity of 80% and a specificity of 95%. In conclusion,
      delayed hypointensity of an arterially-enhancing mass was the strongest
      independent predictor of HCC, regardless of the size of the lesion. If additional
      studies confirm our results, the noninvasive criteria utilized to make a
      diagnosis of HCC should be revised.

PMID- 15719412
TI  - Management of pre-liver transplantation patient--part 2.

PMID- 15719413
TI  - Extracellular diffusion is fast and isotropic in the stratum radiatum of
      hippocampal CA1 region in rat brain slices.
AB  - Molecular transport in brain extracellular space (ECS) is hindered by the
      structure of the tissue. Diffusion analysis of small extracellular markers
      quantifies tissue hindrance, expressed as tortuosity lambda = (D/D*)(1/2), where
      D is the free diffusion coefficient and D* is the effective diffusion coefficient
      in tissue. In healthy brain, lambda is approximately 1.6, but the nature of this
      parameter is poorly understood. We report that the stratum radiatum of the
      hippocampal CA1 region in vitro, previously shown to be anisotropic (i.e.,
      different along the x-, y-, and z-axes) in in vivo study, is isotropic like
      somatosensory neocortex but has a reduced lambda. Diffusion of fluorophore
      labeled dextran (f-dex, M(r) 3,000) and tetramethylammonium (TMA(+), M(r) 74) was
      measured in rat brain slices (400 mum) using integrative optical imaging (IOI)
      and real-time iontophoresis (RTI), respectively. In the stratum radiatum,
      diffusion of f-dex was similar along the x-, y-, and z-axes (lambda(x),
      lambda(y); lambda(z) were 1.55, 1.53, and 1.55), but the tortuosity was
      significantly lower than in the neocortex, where lambda = 1.81. This finding was
      confirmed by the RTI method, which measured lambda with TMA(+), a much smaller
      molecule, and determined volume fraction alpha, the proportion of tissue occupied
      by the ECS. In stratum radiatum, lambda(x), lambda(y), and lambda(z) were 1.47,
      1.44, and 1.46, while in neocortex, lambda was 1.65. The ECS volume fraction was
      similar (0.24) in both regions. It is proposed that in the hippocampus, low
      lambda reflects a reduced occurrence of concave extracellular microdomains,
      referred to as dead spaces, which increase tortuosity by transient trapping of
      markers. Functionally, a low lambda may permit structural plasticity and
      facilitate extrasynaptic communication. It may also enhance the spread of
      neuroactive substances and thus contribute to the sensitivity of the hippocampal
      CA1 region to ischemia and epilepsy.

PMID- 15719414
TI  - Hippocampal 72-kDa heat shock protein expression varies according to mice
      learning performance independently from chronic exposure to stress.
AB  - The possibility that the inducible 72-kDa heat shock protein (hsp72) is involved
      in learning-related plasticity mechanisms was investigated in two inbred strains
      of mice that show spontaneous differences in spatial learning performance as well
      as an opposite reactivity to stress. Induction of hsp72 after radial maze
      training was measured by immunoblotting in the hippocampus of C57BL/6 (C57) and
      DBA/2 (DBA) inbred mice exposed or nonexposed to chronic acoustic stress. In
      agreement with previous studies, inter-strain differences in radial maze
      performance were found in nonstressed mice with C57 mice showing the higher
      scores. Chronic acoustic stress, however, impaired performance in the high
      learner C57 strain and improved performance in the low-learner DBA strain.
      Western blot analysis revealed that post-training expression of hsp72 was low in
      the condition each strain was showing the higher-performance (nonstressed C57 and
      stressed DBA) and high in the condition each strain was showing the lower
      performance (stressed C57 and nonstressed DBA). These findings indicate that
      expression of hsp72 in the hippocampus varies as a function of the learning
      performance independently from exposure to chronic acoustic stress.

PMID- 15719415
TI  - Striatal synaptic plasticity: implications for motor learning and Parkinson's
      disease.
AB  - Changing the strength of synaptic connections between neurons is widely assumed
      to be the mechanism by which memory traces are encoded and stored in the central
      nervous system. Plastic changes appear to follow a regional specialization and
      underlie the specific type of memory mediated by the brain area in which
      plasticity occurs. Thus, long-term changes occurring at excitatory
      corticostriatal synapses should be critically involved in motor learning. Indeed,
      repetitive stimulation of the corticostriatal pathway can cause either a long
      lasting increase or an enduring decrease in synaptic strength, respectively
      referred to as long-term potentiation (LTP), and long-term depression, both
      requiring a complex sequence of biochemical events. Once established, LTP can be
      reversed to control levels by a low-frequency stimulation protocol, an active
      phenomenon defined "synaptic depotentiation," required to erase redundant
      information. In the 6-hydroxydopamine rat model of Parkinson's disease (PD),
      striatal synaptic plasticity has been shown to be impaired, although chronic
      treatment with levodopa was able to restore it. Of interest, a consistent number
      of L-dopa-treated animals developed involuntary movements, resembling human
      dyskinesias. Strikingly, electrophysiological recordings from the dyskinetic
      group of rats demonstrated a selective impairment of synaptic depotentiation.
      This survey will provide an overview of plastic changes occurring at striatal
      synapses. The potential relevance of these findings in the control of motor
      function and in the pathogenesis both of PD and L-dopa-induced motor
      complications will be discussed.

PMID- 15719416
TI  - Gabapentin can improve postural stability and quality of life in primary
      orthostatic tremor.
AB  - Primary orthostatic tremor (OT) is characterized by leg tremor and instability on
      standing. High frequency (13-18 Hz) tremor bursting is present in leg muscles
      during stance, and posturography has shown greater than normal sway. We report on
      an open-label add-on study of gabapentin in 6 patients with OT. Six patients were
      studied with surface electromyography, force platform posturography, and a
      modified Parkinson's disease questionnaire (PDQ-39) quality of life (QOL) scale
      before and during treatment with gabapentin 300 mg t.d.s. If on other medications
      for OT, these were continued unchanged. Of the 6 patients, 4 reported a
      subjective benefit of 50 to 75% with gabapentin, 3 of whom showed reduced tremor
      amplitude and postural sway of up to 70%. Dynamic balance improved in all 3
      patients who completed the protocol. QOL data from 5 patients showed improvement
      in all cases. No adverse effects were noted. Gabapentin may improve tremor,
      stability, and QOL in patients with OT, and symptomatic response correlated with
      a reduction in tremor amplitude and postural sway. The findings confirm previous
      reports of symptomatic benefit with gabapentin and provide justification for
      larger controlled clinical trials. Further work is required to establish the
      optimal dosage and to validate the methods used to quantify the response to
      treatment.

PMID- 15719417
TI  - Patient-perceived involvement and satisfaction in Parkinson's disease: effect on
      therapy decisions and quality of life.
AB  - Patient-centered consultation styles are associated with higher patient
      satisfaction and improved health outcomes in diabetes and hypertension. In
      outpatient neurology, dissatisfaction with communication relates significantly to
      noncompliance. We undertook a single-center study in Parkinson's disease (PD)
      using standardized questionnaires to score patient-perceived involvement in
      therapy decisions (score 4 = low to 25 = high) and satisfaction with the
      consultation (score 1 = low to 7 = high). Correlation was tested against health
      outcomes of Unified Parkinson's Disease Rating Scale (UPDRS) Motor score,
      activities of daily living (UPDRS 2 and Schwab and England), Parkinson's disease
      quality of life (PDQ-39), Mini-Mental State Examination (MMSE), and Geriatric
      Depression Scale (GDS). Of 117 patients enrolled, 107 (91%) fully completed the
      questionnaires. Mean patient-perceived involvement scored 14.4 (SD, 2.8). Mean
      satisfaction scored 5.3 (SD 0.7). Higher involvement was associated with
      increased satisfaction (r = 0.28; P = 0.003), particularly distress relief (r =
      0.38; P < 0.0001). Communication scores correlated significantly with compliance
      intent (r = 0.6; P < 0.0001). There was no correlation between either involvement
      or satisfaction and UPDRS, Schwab and England, MMSE, or GDS. Quality of life was
      significantly associated with depression, UPDRS, duration of PD, compliance
      intent, and satisfaction. The significant positive association between compliance
      intent and quality of life in the more satisfied patient replicates findings in
      other disease areas. Due attention to these aspects in delivering care to the PD
      patient is appropriate.

PMID- 15719419
TI  - Feasibility and validity of a modified finger-nose-finger test.
AB  - In essential tremor (ET) research, it is important to obtain standardized,
      objective data on tremor severity. Often, it is not possible to carry out in
      person or videotaped neurological examinations. In place of these, handwriting
      samples can be collected, but they do not capture all of the variance in tremor
      severity. Although additional tests of tremor severity (finger-nose-finger [FNF]
      test) might be of use, these would need to be modified to allow ET patients to
      mail their results to the study investigator for rating. We modified the standard
      FNF test (sFNF) by asking subjects to hold a pen during this activity and mark a
      paper target. The purpose of this report was to determine whether the modified
      FNF (mFNF) test was feasible and valid. Of 70 subjects, 65 (92.9%) were able to
      complete the mFNF, demonstrating that it was feasible. The scores of the mFNF
      correlated highly with those of the sFNF (r = 0.56-0.85; all P < 0.001),
      indicating the mFNF is a valid measure of tremor severity. In addition, using the
      regression equation, sFNF = 0.174(mFNF) + 0.743, a sFNF score can be derived
      easily from the mFNF score. The mFNF may be used to collect valuable data on
      tremor severity in pathological, genetic, and epidemiological field studies of
      ET, in which in-person or videotaped neurological examinations are not possible.

PMID- 15719418
TI  - Pinocchio, a novel protein expressed in the antenna, contributes to olfactory
      behavior in Drosophila melanogaster.
AB  - Most organisms depend on chemoreception for survival and reproduction. In
      Drosophila melanogaster multigene families of chemosensory receptors and putative
      odorant binding proteins have been identified. Here, we introduce an additional
      distinct protein, encoded by the CG4710 gene, that contributes to olfactory
      behavior. Previously, we identified through P[lArB]-element mutagenesis a smell
      impaired (smi) mutant, smi21F, with odorant-specific defects in avoidance
      responses. Here, we show that the smi21F mutant also exhibits reduced attractant
      responses to some, but not all, of a select group of odorants. Furthermore,
      electroantennogram amplitudes are increased in smi21F flies. Characterization of
      flanking sequences of the P[lArB] insertion site, complementation mapping,
      phenotypic reversion through P-element excision, and expression analysis
      implicate a predicted gene, CG4710, as the candidate smi gene. CG4710 produces
      two transcripts that encode proteins that contain conserved cysteines and which
      are reduced in the smi21F mutant. Furthermore, in situ hybridization reveals
      CG4710 expression in the third antennal segment. We have named this gene of
      previously unknown function and its product "Pinocchio (Pino)".

PMID- 15719420
TI  - Intradermally focused infrared laser pulses: thermal effects at defined tissue
      depths.
AB  - BACKGROUND AND OBJECTIVES: To produce controlled, spatially confined thermal
      effects in dermis. STUDY DESIGNS/MATERIALS AND METHODS: A 1 W, 1,500 nm fiber
      coupled diode laser was focused with a high numerical aperture (NA) objective to
      achieve a tight optical focus within the upper dermis of skin held in contact
      with a glass window. The delivery optics was moved using a computer-controlled
      translator to generate an array of individual exposure spots. Fresh human facial
      skin samples were exposed to a range of pulse energies at specific focal depths,
      and to a range of focal depths at constant pulse energy. Cellular damage was
      evaluated in frozen sections using nitro-blue tetrazolium chloride (NBTC), a
      lactate dehydrogenase (LDH) activity stain. Loss of birefringence due to thermal
      denaturation of collagen was evaluated using cross-polarized light microscopy.
      The extent of focal thermal injury was compared with a model for photon migration
      (Monte Carlo Simulation), heat diffusion, and protein denaturation (Arrhenius
      model). RESULTS: Arrays of confined, microscopic intradermal foci of thermal
      injury were created. At high NA, epidermal damage was avoided without active
      cooling. Foci of thermal injury were typically 50-150 microm in diameter,
      elliptical, and at controllable depths from 0 to 550 microm. Both LDH
      inactivation and extracellular matrix denaturation were achieved. CONCLUSION:
      Spatially confined foci of thermal effects can be achieved by focusing a low
      power infrared laser into skin. Size, depth, and density of microscopic, thermal
      damage foci may be arbitrarily controlled while sparing surrounding tissue. This
      may offer a new approach for nonablative laser therapy of dermal disorders.

PMID- 15719421
TI  - Ciliary neurotrophic factor protects retinal ganglion cells from axotomy-induced
      apoptosis via modulation of retinal glia in vivo.
AB  - Adenoviral-mediated transfer of ciliary neurotrophic factor (CNTF) to the retina
      rescued retinal ganglion cells (RGCs) from axotomy-induced apoptosis, presumably
      via activation of the high affinity CNTF receptor alpha (CNTFRalpha) expressed on
      RGCs. CNTF can also activate astrocytes, via its low affinity leukemia inhibitory
      receptor beta expressed on mature astrocytes, suggesting that CNTF may also
      protect injured neurons indirectly by modulating glia. Adenoviral-mediated
      overexpression of CNTF in normal and axotomized rat retinas was examined to
      determine if it could increase the expression of several glial markers previously
      demonstrated to have a neuroprotective function in the injured brain and retina.
      Using Western blotting, the expression of glial fibrillary acid protein (GFAP),
      glutamate/aspartate transporter-1 (GLAST-1), glutamine synthetase (GS), and
      connexin 43 (Cx43) was examined 7 days after intravitreal injections of Ad.CNTF
      or control Ad.LacZ. Compared to controls, intravitreal injection of Ad.CNTF led
      to significant changes in the expression of CNTFRalpha, pSTAT(3), GFAP, GLAST,
      GS, and Cx43 in normal and axotomized retinas. Taken together, these results
      suggest that the neuroprotective effects of CNTF may result from a shift of
      retinal glia cells to a more neuroprotective phenotype. Moreover, the modulation
      of astrocytes may buffer high concentrations of glutamate that have been shown to
      contribute to the death of RGCs after optic nerve transection.

PMID- 15719423
TI  - Alpha-synuclein mRNA expression in sporadic Parkinson's disease.
AB  - The expression of alpha-synuclein gene can be influenced by the genomic load
      and/or epigenetic factors. By using quantitative real-time polymerase chain
      reaction techniques, we demonstrated that the alpha-synuclein gene mRNA
      expression in sporadic PD did not differ from healthy controls (median [range]
      0.110 ]0.012-0.628] vs. 0.120 [0.028-0.447]; P = 0.15). There was no difference
      in the alpha-synuclein gene dosage between PD patients with high and low mRNA
      expression. Multivariate analysis did not reveal age, gender, or cigarette
      smoking as confounding variables. Our study suggests that there was no
      significant alteration of alpha-synuclein mRNA expression in our sporadic PD
      patients compared to controls. However, the role of alpha-synuclein mRNA
      expression in select groups of sporadic PD patients and its interaction with
      environmental agents need to be further determined.

PMID- 15719422
TI  - Mixed lineage kinase-c-jun N-terminal kinase signaling pathway: a new therapeutic
      target in Parkinson's disease.
AB  - There is growing evidence that the molecular pathways of programmed cell death
      play a role in neurodegenerative disease, including Parkinson's disease, so there
      has been increased interest in them as therapeutic targets for the development of
      neuroprotective strategies. One pathway of cell death that has attracted
      particular attention is the mixed lineage kinase (MLK) -c-jun N-terminal kinase
      (JNK) signaling cascade, which leads to the phosphorylation and activation of the
      transcription factor c-jun. There is much evidence, from in vitro and in vivo
      studies, that this cascade can mediate cell death. In addition, there is evidence
      that it is operative upstream in the death process. It is possible that
      abrogation of this pathway may forestall death before irreversible cellular
      injury. One class of compounds that has shown promise for their ability to block
      cell death by inhibiting this cascade are the inhibitors of the MLKs, which are
      upstream in the activation of c-jun. One of these compounds, CEP1347, is now in a
      Phase II/III clinical trial for neuroprotection in PD. Whether this trial is
      successful or not, this signaling cascade is likely to be a focus of future
      therapeutic development. This review, therefore, outlines the principles of
      signaling within this kinase pathway, and the evidence for its role in cell
      death. We review the evidence that inhibition of the MLKs can prevent dopamine
      neuron cell death and the degeneration of their axons. These studies suggest
      important future directions for the development of therapies that will target
      this important cell death pathway.

PMID- 15719424
TI  - Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist,
      ameliorates constipation in parkinsonian patients.
AB  - Mosapride citrate is a novel selective 5-HT4 receptor agonist. It facilitates
      acetylcholine release from the enteric cholinergic neurons. In contrast to
      cisapride, mosapride does not block K(+) channels or D2 dopaminergic receptors.
      The objective of this study is to perform an open study of mosapride citrate's
      effects on constipation, a prominent lower gastrointestinal tract disorder in
      parkinsonian patients. A total of 14 parkinsonian patients (7 with Parkinson's
      disease, 7 with multiple system atrophy; 10 men, 4 women; mean age, 67 years)
      with constipation (10 with bowel movement < 3 times/week; 14 with difficulty in
      defecation) were treated with 15 mg/day of mosapride citrate for 3 months. Pre-
      and posttreatment objective parameters in colonic transit time (CTT) and
      rectoanal videomanometry were obtained. Statistical analysis was made by
      Student's t test. Mosapride was well tolerated by all patients except for 1, who
      discontinued use of the drug because of epigastric discomfort. None had a
      worsening of parkinsonism or other adverse events. Thirteen patients reported
      subjective improvements in bowel frequency (>3 times/week, 13) and difficult
      defecation (13). Mosapride shortened CTT of the left colon (P < 0.01) and the
      total colon (P < 0.05). During rectal filling, mosapride lessened the first
      sensation (P < 0.05) and augmented the amplitude in phasic rectal contraction.
      During defecation, mosapride augmented the amplitude in rectal contraction (P <
      0.05) and lessened the volume of postdefecation residuals. The present study
      showed for the first time that mosapride citrate augmented lower gastrointestinal
      tract motility, as shown in CTT and videomanometry, and thereby ameliorated
      constipation in parkinsonian patients without serious adverse effects.

PMID- 15719425
TI  - Smell identification ability in twin pairs discordant for Parkinson's disease.
AB  - Olfactory dysfunction has been proposed to be a sign that may precede the motor
      features of Parkinson's disease (PD). To determine whether smell identification
      deficits predict subsequent PD, we studied smell identification ability using the
      University of Pennsylvania Smell Identification Test (UPSIT) in 62 members of
      male twin pairs discordant for PD at baseline. Smell identification ability was
      reduced at baseline in the twins with PD compared to their unaffected brothers
      (23 vs. 31 of 40; P = 0.001). UPSIT scores were not reduced in the twins without
      PD when compared to age- and gender-specific normal values. After a mean interval
      of 7.3 years, 28 unaffected twins were still alive and 19 agreed to a second
      evaluation. Two had newly developed PD. Neither twin had impaired smell
      identification at baseline. The average decline in UPSIT percentile scores in
      these 2 twins was greater than in the 17 twins who did not develop PD (-68% vs. 
      24%; P = 0.01). In subjects who did not meet Core Assessment Program for
      Intracerebral Transplantations diagnostic criteria for PD at baseline, the
      presence of cardinal signs of parkinsonism was not associated with lower baseline
      UPSIT scores nor with a subsequent decline. Smell identification ability may not
      be a sensitive indicator of future PD 7 or more years before the development of
      motor signs, even in a theoretically at-risk population.

PMID- 15719426
TI  - Identification of motor and nonmotor wearing-off in Parkinson's disease:
      comparison of a patient questionnaire versus a clinician assessment.
AB  - This study compares the sensitivity of a Patient Questionnaire versus information
      gathered by clinicians at a routine clinic visit in recognizing symptoms of
      wearing-off in early Parkinson's disease (PD). This Patient Questionnaire,
      containing 32 items representing a wide spectrum of motor and nonmotor wearing
      off symptoms, was administered to subjects attending two PD clinics. The Patient
      Questionnaire results were compared to the information gathered by the clinician
      from the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV, Question 36
      and from a specific Clinical Assessment Question regarding loss of medication
      efficacy, wearing-off, sleepiness, dyskinesias, psychiatric complications,
      morning akinesia, other dopaminergic side effects, or none of the above.
      Examiners were blinded to study hypothesis and survey contents. Three hundred
      consecutive subjects with PD of <5 years duration were evaluated; the mean
      subject age was 72 +/- 9.6 years and 60.2% were men. Subjects reporting wearing
      off were significantly younger (69.9 vs. 74.7 years) and differed regarding
      duration of PD symptoms (3.7 vs. 3.1 years). Wearing-off was found in 181
      subjects (62.6%) by one or more of the three measures. The most sensitive tool
      was the Patient Questionnaire, with 165 subjects (57.1%) indicating symptoms of
      wearing-off. Question 36 of the UPDRS was positive in 127 subjects (43.9%), and
      the Clinical Assessment Question identified 85 subjects (29.4%) as experiencing
      wearing-off. All of these results were found to differ significantly. The mean
      number of wearing-off symptoms reported by the 165 subjects indicating wearing
      off on the clinical survey was 6.25, with tremor being the most common motor
      feature and tiredness the most common nonmotor feature.

PMID- 15719428
TI  - PEG-grafted chitosan as an injectable thermoreversible hydrogel.
AB  - PEG-grafted chitosan was formulated such that its solution undergoes a thermally
      reversed phase transition from an injectable free-flowing solution at low
      temperature to a gel at body temperature. Aqueous solutions of PEG-grafted
      chitosan can be prepared at physiological pH values, thereby allowing safe
      incorporation of bioactive molecules. This injectable thermoreversible hydrogel
      is potentially suitable for a wide range of biomedical applications, particularly
      in sustained in vivo drug release and tissue engineering. An aqueous solution of
      PEG-grafted chitosan polymer is injectable at low temperatures but forms a gel at
      body temperature.

PMID- 15719427
TI  - Antiparkinson medications improve agonist activation but not antagonist
      inhibition during sequential reaching movements.
AB  - The execution of sequential arm movements is critical to activities of daily
      living such as eating and grooming. It is known that movement sequences are
      bradykinetic in people with Parkinson's disease (PD) and that antiparkinson
      medications improve the speed of movement sequences. However, it is unclear how
      muscle activity is modulated during sequential movements and what effect
      antiparkinson medications have on muscle modulation. We studied subjects with PD
      and age- and gender-matched control subjects making sequential reaching
      movements. Subjects with PD were tested before and after their morning dose of
      antiparkinson medications (levodopa and/or dopamine agonists). We examined the
      effect of antiparkinson medications on the modulation of muscle activity (i.e.,
      the ability to activate and inhibit each muscle throughout the course of a
      sequence). Results showed that the group with PD, before medication, moved more
      slowly and modulated muscle activity poorly compared to the control group.
      Antiparkinson medications improved movement speed as expected, although
      sequential movements remained slower than normal even after medication.
      Medication improved the ability to activate agonist muscle activity but did not
      improve the ability to inhibit antagonist activity. Instead, antagonist activity
      was also increased, resulting in minimal improvements in muscle modulation during
      sequential reaching movements.

PMID- 15719429
TI  - Morphology and structure of hemp fibre after bioscouring.
AB  - Bioscouring of hemp (Cannabis Sativa L) using pectate lyase (EC 4.2.2.2),
      Scourzyme L, was performed at 55 degrees C and pH 8.5 in a nonagitated system.
      The enzyme concentration, treatment time and substrate concentration were varied
      to obtain the kinetic constants, K(m) and V(m). Greater enzyme concentration and
      a longer treatment improved the removal of the low methoxy pectin component as
      indicated by UV spectroscopy. Removal of pectate caused no crystalline
      transformation in the fibres, except for a slight decline in the crystallinity
      order index analysed by Fourier Transform infrared spectroscopy and wide angle X
      ray diffraction. This corresponded well with the single fibre bundle tensile
      mechanical properties test. Smooth surfaces and separated fibres observed using
      SEM images were evidence of successful treatment, supported by weight loss at low
      temperature of a pectic substance. After treatment, the pectin substance was no
      longer observed during thermogravimetry. An increase in surface area and pore
      size after scouring were further evidence of modification.

PMID- 15719430
TI  - Influence of satellite groups on telechelic antimicrobial functions of
      polyoxazolines.
AB  - The antimicrobial activity of poly(alkyloxazoline) telechelics with one
      quaternary N,N-dimethyldodecylammonium (DDA) end group was found to be greatly
      controlled by the non-bioactive distal end group, the so-called satellite group.
      In systematic investigations, the nature of the latter groups was varied to
      explore the mechanism of the satellite effect. To this end, poly(2-alkyl-1,3
      oxazoline)s (alkyl = ethyl, methyl) with a DDA-group at the terminating end and
      varying alkyl, aminoalkyl, and polyphenyloxazoline block satellite groups, have
      been synthesized. Poly(oxazoline) derivatives with polydispersity indices of 1.06
      1.20 and molecular weights from 2,200 to 12,800 g . mol(-1) could be obtained.
      The macromolecular structures have been confirmed by NMR spectroscopy and ESI-MS
      measurements. The polymers were investigated with regard to their antibacterial
      efficiency towards the Gram-positive bacterium Staphylococcus aureus and the Gram
      negative bacterium Escherichia coli. It was found that the introduction of alkyl
      chain satellites of 4-10 carbon atoms in length afforded antimicrobial activity
      of the polymers against both microbes that was about 2-3 times higher than that
      of the well-known structurally comparable low molecular weight biocide,
      dodecyltrimethylammonium chloride (DTAC). Based on the antimicrobial effects of
      the investigated polymers, a mechanism for the satellite effect was proposed.

PMID- 15719431
TI  - Intelligent crew-cut aggregates formed by thermosensitive block copolymers and
      their multiple morphologies.
AB  - The thermosensitive block copolymer poly(2-cinnamoylethyl methacrylate)-block
      poly(N-isopropylacrylamide) (PCEMA-b-PNIPAAm) can form crew-cut aggregates with
      multiple morphologies under various micellization conditions. Spherical, rod
      like, vesicular, lamellar aggregates, and large compound micelles were obtained
      from the block copolymers. The effects of different conditions, such as the
      copolymer composition, the nature of the common solvent, the initial copolymer
      concentrations, and the water content on the morphologies of the aggregates were
      studied in detail. The thermosensitive property of the aggregates was
      investigated through measuring the change of the dimension of the aggregates with
      changing the external temperature.

PMID- 15719432
TI  - Low-molecular-weight poly(alpha-methyl beta,L-malate) of microbial origin:
      synthesis and crystallization.
AB  - Low-molecular-weight poly(alpha-methyl beta,L-malate) made of approximately 25-30
      units was prepared from microbial poly(beta,L-malic acid) by treatment with
      diazomethane. The thermal characterization of the polymalate methyl ester was
      carried out and its crystalline structure was preliminary examined. Its ability
      to crystallize both from solution and from the melt was comparatively evaluated.

PMID- 15719433
TI  - Case of neuroleptic malignant-like syndrome precipitated by abrupt fava bean
      discontinuance.
AB  - Neuroleptic malignant-like syndrome (NMLS) is well described in the treatment of
      Parkinson's disease. The syndrome is characterized by fever, rigidity, autonomic
      instability, elevated creatine phosphokinase levels, and altered level of
      consciousness, which is usually precipitated by levodopa withdrawal. In recent
      years, patients have used fava beans to treat Parkinson's symptoms, because the
      beans contain appreciable amounts of levodopa and have been thought to be a safe
      adjunctive therapy. We describe a case of NMLS, which was precipitated by the
      abrupt cessation of fava bean ingestion.

PMID- 15719434
TI  - Interaction between eye and hand movements in multiple sclerosis patients with
      intention tremor.
AB  - Deficient eye and hand movements are present in patients with multiple sclerosis.
      In the present study, eye and hand movements were simultaneously measured during
      visually guided wrist step-tracking tasks in 16 patients with intention tremor
      and 15 healthy controls. The coupling between eye and hand movements was analyzed
      during simultaneous eye-hand tracking, and interactions were studied by comparing
      the coordinated eye-hand condition with isolated eye- or hand-tracking
      conditions. Despite movement abnormalities, the onset of eye and hand movements
      was highly correlated and an invariant coupling between the saccadic completion
      time and hand peak velocity was found, suggesting that the temporal coupling was
      very much preserved. The differences between the experimental tracking conditions
      suggest that, in MS patients with intention tremor, the ocular system influenced
      the hand movements. Intention tremor amplitude was reduced when there was no
      preceding saccadic eye movement, whereas conversely, eye movements were not
      affected by different hand tremor severity.

PMID- 15719436
TI  - Immunohistochemically detected lymph node metastases from breast carcinoma:
      practical considerations about the new American Joint Committee on Cancer
      classification.
AB  - BACKGROUND: The authors applied the sixth edition of the American Joint Committee
      on Cancer (AJCC) classification system to their previously published group of
      patients with breast carcinoma who had immunohistochemically detected lymph node
      metastases. METHODS: The original lymph node-negative slides from 218 patients,
      including 129 patients with infiltrating duct carcinoma (IDC) and 89 patients
      with infiltrating lobular carcinoma (ILC), were reviewed and then destained to
      perform immunohistochemistry. Each tumor cell deposit was measured. Single tumor
      cells could not counted or measured (because the distance separating the most
      distant cells could be > 2.0 mm), but they were separated into Class 1 (sparse)
      and Class 2 (numerous). According to the AJCC classification, isolated tumor
      cells (ITCs) should be classified as pN0(i+) when they measure < or = 0.2 mm and
      pN1mi when they measure < or = 2.0 mm but > 0.2 mm. RESULTS: ITCs were found in
      13 IDCs (10%) and in 37 ILCs (41%) and corresponded in IDCs to a single deposit
      of a few tumor cells that measured < or = 0.2 mm (associated with a single tumor
      cell in 3 tumors) and were classified as pN0(i+). In ILCs, ITCs corresponded to
      single tumor cells with an irregular distribution throughout the entire lymph
      node section (24 ITCs and 13 ITCs in Class 1 and Class 2, respectively) and were
      difficult to classify. CONCLUSIONS: The results suggest that there are 2
      categories of pN0(i+): measurable tumor cell deposits < or = 0.2 mm, which were
      found exclusively in IDCs; and nonmeasurable ITCs, which were found in ILCs and
      rarely in IDCs. The new classification is difficult to apply to ITCs that are
      detected by immunohistochemistry in ILCs.

PMID- 15719437
TI  - More on epistasis.

PMID- 15719438
TI  - Resistance to caspase-dependent, hypoxia-induced apoptosis is not hypoxia
      inducible factor-1 alpha mediated in prostate carcinoma cells.
AB  - BACKGROUND: Hypoxia occurs in association with cancer development, the result
      being a more aggressive and metastatic cancer phenotype. Hypoxia, which activates
      hypoxia-inducible factor-1 alpha (HIF-1alpha), is associated with a number of
      cellular changes including increased apoptotic resistance. The authors
      hypothesized that HIF-1alpha is central to the cell's ability to resist apoptosis
      induced during the hypoxia selection process. METHODS: PWR-1E, LNCaP, LNCaP-HOF,
      PC-3, and DU-145 cells were cultured in normoxic and hypoxic conditions.
      Apoptosis was assessed by propidium iodide DNA staining. Cleavage of specific
      substrates was used to assess caspase activity and Western blotting was used to
      assess mitochondrial release of cytochrome c and second mitochondria-derived
      activator caspase (SMAC)/Diablo. A dominant negative HIF-1alpha construct was
      transfected into the PC-3 and LNCaP cells to block HIF-1alpha activity. RESULTS:
      PC-3 and DU-145 were resistant to apoptosis induced by exposure to hypoxia, but
      the PWR-1E and LNCaP cells were susceptible. This induction of apoptosis in the
      LNCaP cells was caspase dependent but independent of cytochrome c release.
      Blocking the activity of HIF-1alpha had no effect on increased apoptotic
      susceptibility in the PC-3 cells. LNCaP-HOF cells, which were resistant to
      hypoxia-induced apoptosis, showed no increase in HIF-1alpha expression or
      activity. CONCLUSIONS: Apoptotic resistance is already established in cells that
      survive a hypoxic insult and whereas increased HIF-1alpha activity may be
      essential for the development of a more aggressive cancer phenotype, it may not
      be responsible for the initial selection of an apoptotic resistance phenotype.

PMID- 15719439
TI  - Sequential topotecan and oral etoposide in recurrent ovarian carcinoma pretreated
      with platinum-taxane. Results from a multicenter phase I/II study.
AB  - BACKGROUND: The objectives of this study were to determine the maximum tolerable
      dose (MTD), toxicity, efficacy, and feasibility of a sequential regimen of fixed
      dose topotecan (1.00 mg/m2 on Days 1-5) and increasing doses of oral etoposide
      (50 mg, 75 mg, and 100 mg on Days 6-12 or Days 6-19) in patients with recurrent
      ovarian carcinoma. METHODS: This multicenter, open-label study was planned as a
      Phase I-II study that included patients with epithelial ovarian carcinoma who
      failed or who developed recurrent disease < 12 months after the end of platinum
      and taxane-containing chemotherapy. Dose-limiting toxicity (DLT) was defined as
      follows: Grade 4 neutropenia for > 1 week, or neutropenic fever 38.5 degrees C
      for > 24 hours/sepsis, or Grade 4 thrombocytopenia for > 1 week, or
      thrombocytopenia with bleeding, or Grade 3-4 nonhematologic toxicity. RESULTS:
      The MTD, as defined in the protocol, could not be settled because of
      unpredictable toxicity, because DLT was found at all dose levels except the
      starting dose level. In 28 patients (Phase I), 155 cycles were evaluable for
      toxicity. The main DLT was neutropenia Grade 4 for > 1 week or neutropenic
      fever/sepsis. Overall, neutropenia Grade 4 that lasted > 1 week and sepsis were
      noticed in 3% and 2% of cycles, respectively. Because no MTD was reached, the
      planned Phase II trial was not initiated. However, the patients from Phase I were
      followed until they developed progressive disease and, among them, 9 patients
      (32%) obtained an objective response (according to Response Evaluation Criteria
      in Solid Tumors (RECIST) or CA125 response criteria). CONCLUSIONS: Combined
      topotecan and oral etoposide was inappropriate in patients with recurrent ovarian
      carcinoma because of unpredictable hematologic toxicity. However, the high
      objective response rate highlighted the potential additive effect of
      topoisomerase I and II inhibitors.

PMID- 15719440
TI  - Posttherapy pathologic stage predicts survival in patients with esophageal
      carcinoma receiving preoperative chemoradiation.
AB  - BACKGROUND: In patients with locoregional carcinoma of the esophagus or
      esophagogastric junction who underwent preoperative chemoradiation, it is unclear
      whether survival was better predicted by pretherapy clinical stage or by
      posttherapy pathologic stage. METHODS: The authors studied 235 consecutive
      patients with pretherapy clinical Stage II, III, or IVA (according to American
      Joint Committee on Cancer criteria) carcinoma of the esophagus or esophagogastric
      junction who were treated with chemoradiation followed by esophagectomy.
      Posttherapy cancer status was classified using pathologic stage and
      semiquantitative assessment of residual carcinoma. Clinicopathologic features,
      residual carcinoma status, and pretherapy and posttherapy stage were compared
      with disease-free and overall survival. RESULTS: Posttherapy pathologic stage was
      Stage 0 in 29% of patients, Stage I in 11% of patients, Stage II in 34% of
      patients, Stage III in 20% of patients, and Stage IV in 6% of patients. Cancer
      downstaging occurred in 56% of patients. In univariate analysis, disease-free and
      overall survival were predicted by posttherapy pathologic stage (both with P <
      0.001), margin status (P = 0.002 and P = 0.01, respectively), extent of residual
      carcinoma (both with P < 0.001), and downstaging (both with P = 0.001), but not
      by age, gender, type of cancer, pretherapy clinical stage, or preoperative
      regimen. However, in multivariate analysis, disease-free and overall survival
      were independently predicted by posttherapy pathologic stage (both with P =
      0.02). Extent of residual carcinoma was a marginally significant predictor of
      overall survival (P = 0.04). CONCLUSIONS: Posttherapy pathologic stage was the
      best available predictor of outcome for patients with locoregional carcinoma of
      the esophagus or esophagogastric junction who underwent chemoradiation therapy
      followed by esophagectomy. The findings in the current study supported the
      concept of downstaging by preoperative therapy.

PMID- 15719441
TI  - First-trimester fetuses with increased nuchal translucency do not show altered
      intracardiac flow velocities.
AB  - OBJECTIVE: To study intracardiac flow velocities in first-trimester fetuses with
      normal nuchal translucency thickness (NT) and those with increased NT. METHODS:
      Ultrasound examinations were performed in 85 normal fetuses and 45 fetuses with
      NT > 95(th) percentile. Follow-up was complete and postmortem examination was
      performed on terminated pregnancies. Flow velocities during the early (e-wave)
      and late (a-wave) peaks across the tricuspid and mitral valves were measured and
      compared, using multilevel analysis, between the fetuses with normal and those
      with increased NT. In the group with increased NT, fetuses with and without a
      heart defect irrespective of the karyotype were compared, and in this group,
      euploid and aneuploid fetuses were compared, irrespective of the presence of a
      heart defect. RESULTS: No difference in intracardiac flow velocities was found
      between fetuses with normal and those with increased NT. Within the group of
      fetuses with increased NT, there was no difference between the fetuses with and
      without a cardiac defect. However, comparison of aneuploid with euploid fetuses
      within the group with increased NT showed that both the e-wave and a-wave peaks
      were decreased significantly by 3.03 cm/s and 5.95 cm/s, respectively, across the
      tricuspid valve, and by 3.47 cm/s and 5.92 cm/s, respectively, across the mitral
      valve (P < 0.05). The most common cardiac malformations were septal defects.
      CONCLUSION: There is no difference in intracardiac blood flow velocities between
      normal fetuses and those with increased NT. This contradicts the theory that NT
      is caused by impaired atrial contraction or cardiac failure. In fetuses with
      increased NT, those with aneuploidy show a decreased e-wave and a-wave compared
      with euploid fetuses. This cannot, however, be explained by the presence of
      cardiac defects, because there is no difference between fetuses with and without
      a cardiac defect. Therefore, we hypothesize that the relationship between
      enlarged NT and cardiac defects can only be explained by a developmental process
      that coexists at this period of gestation and is linked to cardiovascular
      development.

PMID- 15719442
TI  - Unprecedented opportunity to fight HIV/AIDS and change the course of history.

PMID- 15719443
TI  - Surge in demand leads to shortage of artemisinin-based combination therapy for
      malaria.

PMID- 15719444
TI  - Lymphoma-infiltrating immune cells.

PMID- 15719445
TI  - Lymphoma-infiltrating immune cells.

PMID- 15719446
TI  - Interns' work hours.

PMID- 15719447
TI  - Interns' work hours.

PMID- 15719448
TI  - Interns' work hours.

PMID- 15719449
TI  - Interns' work hours.

PMID- 15719450
TI  - Interns' work hours.

PMID- 15719451
TI  - The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.

PMID- 15719453
TI  - Family history.

PMID- 15719452
TI  - The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.

PMID- 15719454
TI  - Family history.

PMID- 15719455
TI  - Doctors and drug companies.

PMID- 15719456
TI  - In that case: Karen is 31-year-old woman who suffers from schizophrenia and has
      been treated with an anti-psychotic medication for a number of years. Commentary.

PMID- 15719457
TI  - In that case: Karen is a 31-year-old woman who suffers from schizophrenia and has
      been treated with an anti-psychotic medication for a number years. Commentary.

PMID- 15719458
TI  - In that case: Mrs A and her husband, Mr A, consulted different GPs at the same
      medical centre. Response.

PMID- 15719459
TI  - In that case: Mrs A and her husband, Mr A, consulted different GPs at the same
      medical centre. Response.

PMID- 15719460
TI  - 488 days and counting...

PMID- 15719461
TI  - Resistance reshufflings (or refining the law of higgledy-piggledy). XIII
      International HIV drug resistance workshop, June 8-12, 2004, Tenerife, Canary
      Islands.

PMID- 15719462
TI  - Focus on hepatitis. Glimpses of hope on a distant horizon.

PMID- 15719463
TI  - The importance of dental care.

PMID- 15719464
TI  - CM4: an herbal supplement with clinical data support.

PMID- 15719465
TI  - ASP's new prevention department.

PMID- 15719466
TI  - The dangers of using and abusing Viagra.

PMID- 15719467
TI  - SAMHSA to issue grants for HIV prevention.

PMID- 15719468
TI  - Canadian health minister releases new initiative to address HIV/AIDS.

PMID- 15719469
TI  - AIDS death in home for retarded not due to negligence.

PMID- 15719470
TI  - Sheriff's mistrust of detective's HIV identifications not libelous.

PMID- 15719471
TI  - Satirist shakes up AIDS politics in new sketches.

PMID- 15719472
TI  - Media. Global volunteers create new HIV/AIDS prevention message.

PMID- 15719473
TI  - Immigration. HIV-positive status insufficient to gain asylum for felon.

PMID- 15719474
TI  - Prisons. Hormone therapy order upheld for man with AIDS.

PMID- 15719475
TI  - AIDS testing order upheld on appeal.

PMID- 15719476
TI  - Medical marijuana. Prosecutors rapped for undermining compassionate use law.

PMID- 15719477
TI  - Ineffective counsel. Court: fair trial did no hinge on dying man's testimony.

PMID- 15719479
TI  - Prevention. Red Cross blood donation query too risque for teens.

PMID- 15719478
TI  - Bias. Lambda urges Denver to uphold legal HIV protections.

PMID- 15719480
TI  - Recent findings from the National Institute of Nursing Research related to
      neonatal care.
AB  - This annotated bibliography from the National Institute of Nursing Research
      (NINR) presents recent findings on the management of high-risk pregnancy and on
      neonatal care from delivery trough long-term follow-up. By sharing this
      bibliography, we hope to increase the awareness of these valuable research
      findings within the nursing community and support the continued development of
      evidence-based practice.

PMID- 15719482
TI  - [78th annual meeting of the Japanese Association for Infectious Diseases. Tokyo,
      Japan. April 6-7, 2004. Abstracts].

PMID- 15719481
TI  - PLGA nanoparticles in drug delivery: the state of the art.
AB  - Nanoparticles represent drug delivery systems suitable for most administration
      routes. Over the years, a variety of natural and synthetic polymers have been
      explored for the preparation of nanoparticles, of which Poly(lactic acid) (PLA),
      Poly(glycolic acid) (PGA), and their copolymers (PLGA) have been extensively
      investigated because of their biocompatibility and biodegradability.
      Nanoparticles act as potential carries for several classes of drugs such as
      anticancer agents, antihypertensive agents, immunomodulators, and hormones; and
      macromolecules such as nucleic acids, proteins, peptides, and antibodies. The
      options available for preparation have increased with advances in traditional
      methods, and many novel techniques for preparation of drug-loaded nanoparticles
      are being developed and refined. The various methods used for preparation of
      nanoparticles with their advantages and limitations have been discussed. The crux
      of the problem is the stability of nanoparticles after preparation, which is
      being addressed by freeze-drying using different classes of lyoprotectants.
      Nanoparticles can be designed for the site-specific delivery of drugs. The
      targeting capability of nanoparticles is influenced by particle size, surface
      charge, surface modification, and hydrophobicity. Finally, the performance of
      nanoparticles in vivo is influenced by morphological characteristics, surface
      chemistry, and molecular weight. Careful design of these delivery systems with
      respect to target and route of administration may solve some of the problems
      faced by new classes of active molecules.

PMID- 15719483
TI  - [The 40th autumn meeting of the Japan Radiological Society. Tokyo, Japan. October
      28-30, 2004. Abstracts].

PMID- 15719484
TI  - [Regional meeting of the Japanese Society of Otolaryngology. Japan.  2003, 2004.
      Abstracts].

PMID- 15719485
TI  - Aspergillus fumigatus isolated from ornamental plants in India.

PMID- 15719486
TI  - Efficacy of Narayan stain for morphological studies of moulds, yeasts and algae.

PMID- 15719488
TI  - 3-Methylglutaconic aciduria: a common biochemical marker in various syndromes
      with diverse clinical features.

PMID- 15719489
TI  - [Spontaneous posterior sphenoid sinus fistula].
AB  - OBJECTIVE: Describe a rare localization of spontaneous cerebrospinal fistula.
      CASE REPORT: A 75-year-old women was admitted for bacterial meningitis arising
      from a sinus infection. She had not experienced facial or head trauma. The CT
      scan revealed pneumocephaly and a defect in the posterior part of the sphenoid
      sinus. DISCUSSION: Spontaneous cerebrospinal fistula is uncommon. The exact
      etiology remains unknown.

PMID- 15719490
TI  - Phase I study of concomitant chemoradiation with raltitrexed in locally advanced
      head and neck cancer.
AB  - In patients with non-resectable head and neck cancer concomitant
      chemoradiotherapy is increasingly used, especially in cases of oropharyngeal and
      hypopharyngeal tumours. Most chemoradiotherapy regimes contain cisplatin as a
      single agent or in combination with fluorouracil. However, not all patients are
      fit enough for a cisplatin-containing regime or they refuse hospital admission.
      Raltitrexed is a specific thymidylate synthase inhibitor that has been studied as
      a radiosensitiser in rectal cancer. Raltitrexed can be administered easily in an
      outpatient setting and has few short-term effects. We studied raltitrexed at
      escalating doses combined with standard radiotherapy in advanced head and neck
      cancer patients. Seventeen patients with locally advanced head and neck cancers
      were enrolled in the study. Raltitrexed was administered at dose levels of 1.5,
      2.0, 2.5 and 3.0 mg/m(2) intravenously (i.v), once every 3 weeks, for two doses.
      Radiotherapy consisted of 70 Gy given over 7 weeks in five fractions of 2 Gy per
      week. In general, treatment toxicity (DLT), complicated febrile neutropenia, was
      observed at 3.0 mg/m(2) in two of four patients. The dose of 2.5 mg/m(2) was
      extended thereafter with additional patients without major toxicity. Radiotherapy
      had to be interrupted in one patient. Five patients had a clinical complete
      response(CR) and eleven a partial response (PR) six weeks after the last fraction
      of radiotherapy. Twelve out of 17 patients remained free of locoregional
      recurrence after a median follow-up of 24(+) months (range 3-60+ months).
      Raltitrexed, at a dose of 2.5 mg/m(2) given twice 3 weeks apart, can be
      administered in combination with 70 Gy of radiotherapy in locally advanced head
      and neck cancer patients with a manageable tolerability profile. The clinical
      results and convenience of the schedule make raltitrexed an attractive drug to
      explore further in patients considered unfit for cisplatin-containing
      chemoradiation regimens.

PMID- 15719491
TI  - Commons ignorance: the failure of environmental law to produce needed information
      on health and the environment.
AB  - One of the most significant problems facing environmental law is the dearth of
      scientific information available to assess the impact of industrial activities on
      public health and the environment. After documenting the significant gaps in
      existing information, this Article argues that existing laws both exacerbate and
      perpetuate this problem. By failing to require actors to assess the potential
      harm from their activities, and by penalizing them with additional regulation
      when they do, existing laws fail to counteract actors' natural inclination to
      remain silent about the harms that they might be causing. Both theory and
      practice confirm that when the stakes are high, actors not only will resist
      producing potentially incriminating information but will invest in discrediting
      public research that suggests their activities are harmful. The Article concludes
      with specific recommendations about how these perverse incentives for ignorance
      can be reversed.

PMID- 15719492
TI  - Multicentre audit of the treatment of uncomplicated urinary tract infection in
      South Thames.
AB  - A regional audit report on the management of uncomplicated urinary tract
      infections (UTIs) in genitourinary (GU) medicine clinics in the UK in South
      Thames (South London, Kent, Surrey and Sussex). The majority of centres use
      trimethoprim as first-line treatment for uncomplicated UTIs. The incidence of
      trimethoprim resistance was 22.6%. The group has therefore recommended that
      cephalexin should be the first choice antibiotic for suspected UTIs within GU
      medicine.

PMID- 15719493
TI  - The crime scene and the method MOCCI.

PMID- 15719494
TI  - Crime scene analysis: daily approach in a French research section.

PMID- 15719496
TI  - Managing data mining at digital crime investigation.

PMID- 15719495
TI  - Genes and human behavior: the emerging paradigm.
AB  - The physical properties of human beings and other organisms as well as their
      social behavioral traits are manifestations of both genetic inheritance and
      environment. Recent behavioral research has indicated that certain
      characteristics or behaviors--such as schizophrenia, divorce, and homosexuality-
      are highly heritable and are not governed exclusively by social environment. A
      balanced view of human behavior includes the effects of social learning as well
      as of genetically determined behavior. A new paradigm promotes enhanced
      understanding and acceptance of human diversity, be it cultural, racial, or
      sexual, and has the potential to unite scientists and theologians by creating
      common grounds of understanding.

PMID- 15719497
TI  - Forensic medicine trends in Lithuania in the European context.

PMID- 15719498
TI  - The response of health care workers to AIDS patients' requests for euthanasia.
AB  - This paper reports on research into the practice of euthanasia amongst Australian
      health care professionals specializing in HIV/AIDS. It draws on data from thirty
      nine semi-structured interviews carried out in Sydney, Melbourne, Brisbane and
      Canberra with physicians, general practitioners, hospital and community nurses,
      therapists and community workers. Using a qualitative methodology, the study
      seeks to identify how (illegal) euthanasia is currently practised, the degrees of
      involvement, the various forms that involvement takes, and the social relations
      which provide the context for involvement. In this paper we outline three
      categories of 'doers' to illustrate the range of attitudes and practices
      concerning euthanasia. This 'typology' carries a number of implications for
      recent policy debates over the legalisation of euthanasia. In particular it
      illustrates, at least within the context of AIDS care, the fragmentation of
      consensus over euthanasia amongst health care workers, the reality of current
      illegal euthanasia practices, and the limitations of a prohibitionist policy.
      While the legalisation of euthanasia within a regulatory framework is sometimes
      portrayed as an extreme or 'radical' response to terminal illness, the data
      presented in this paper suggest that prohibitionism is also radical in its
      failure to control euthanasia practice.

PMID- 15719499
TI  - PAM-1, a natural human IgM antibody as new tool for detection of breast and
      prostate precursors.
AB  - Early detection and differential analysis of premalignant lesions are very
      important for both prognosis and therapy of cancer patients. A good source of
      diagnostic tools is the natural antibody pool of humans. Tumor-specific
      antibodies can be established by using hybridoma technology. The fully human
      germline-coded monoclonal IgM antibody PAM-1 was isolated from a patient with a
      stomach carcinoma. PAM-1 reacts with a post-transcriptionally modified isoform of
      membrane receptor CFR-1 which is overexpressed on almost all epithelial cancers
      of all types and origins. The expression of CFR-1/PAM-1 on precancerous stages of
      breast and prostate cancer was analyzed by immunohistochemistry and compared with
      normal breast and prostate tissue as well as adenocarcinomas of both. In addition
      FACS analysis was performed to detect receptor expression on benign and malign
      prostate cells. 73 different tissue samples of prostate and breast precancerous
      stages and prostate and breast carcinomas were analysed for CFR-1/PAM-1
      expression immunohistochemically. The CFR-1/PAM-1 receptor was expressed on
      nearly all precancerous stages and carcinomas while normal breast and prostate
      tissue showed negative results. These results were confirmed by FACS analysis
      showing a CFR-1/PAM-1 expression only on prostate carcinoma cells but not on
      benign prostate hyperplasia cells. The unique expression of this new CFR-1/PAM-1
      receptor makes the PAM-1 antibody an ideal diagnostic and even therapeutic tool
      for precancerous and cancerous epithelial lesions of the breast and the prostate.

PMID- 15719500
TI  - Swelling behavior and mechanical properties of poly(acrylamide-co-itaconic acid)
      hydrogels and their semi-IPNS with poly(ethylene glycol).

PMID- 15719502
TI  - A preliminary investigation of ethical problems in publication and research.
AB  - This paper describes a preliminary study investigating the nature of publication
      and research ethics problems encountered by psychologists. Descriptions of 25
      ethical dilemmas were written by 22 psychologists. Those dilemmas involved
      conflicts about authorship credit (13), plagiarism (9), unethical research (1),
      and other related problems (2). Stage of career did not determine the likelihood
      of their being confronted with an ethical dilemma. The most often cited causes of
      problems and sources of distress were unethical demands by more dominant
      individuals who were perceived to hold power over the respondents.

PMID- 15719501
TI  - Natural law and the "right to die".
AB  - Over the last two decades social concerns with the "right to die" have grown
      beyond the ability of our governmental and judicial institutions to consistently
      deal with them. One reason for this difficulty has been the unavailability of any
      legal or judicial standard that is consistent with American conceptions of
      liberty, morality, and justice. This article attempts to examine the theory of
      natural law to determine whether it may provide a consistent standard for
      resolving these difficult questions. As natural law theories are traced through
      history, they lead directly to the United States where a uniquely American
      interpretation became one of the foundational principles for our constitution. By
      applying these theories to the contemporary question of the "right to die,"
      natural law can again provide the foundational principles needed to develop
      standards for dealing with such questions that are consistent with our
      historical, philosophical, and political traditions.

PMID- 15719503
TI  - Effect of loading on a swelling-controlled drug delivery system studied by
      optical techniques.

PMID- 15719504
TI  - Preparing for sudden death or organ donation: an ethical dilemma in social work.

PMID- 15719505
TI  - Ethical issues in livestock cloning.
AB  - Although cloning may eventually become an important technology for livestock
      production, four ethical issues must be addressed before the practice becomes
      widespread. First, researchers must establish that the procedure is not
      detrimental to the health or well-being of affected animals. Second, animal
      research institutions should evaluate the net social benefits to livestock
      producers by weighing the benefits to producers against the opportunity cost of
      research capacity lost to biomedical projects. Third, scientists should consider
      the indirect effects of cloning research on the larger ethical issues surrounding
      human cloning. Finally, the market structure for products of cloned animals
      should protect individual choice, and should recognize that many individuals find
      the prospect of cloning (or consuming cloned animals) repugnant. Analysis of
      these four issues is complicated by spurious arguments alleging that cloning will
      have a negative impact on environment and genetic diversity.

PMID- 15719506
TI  - Experimental and theoretical study of the release kinetics of propranolol
      hydrochloride from PVA matrices.

PMID- 15719507
TI  - Bioethics: then and now.

PMID- 15719508
TI  - Dialogue: prenatal diagnosis.

PMID- 15719509
TI  - Ask the ethicist: would you tell the patients?

PMID- 15719510
TI  - Why psychiatrists should not participate in euthanasia and physician-assisted
      suicide.
AB  - Public and professional discussions have recently raised the question of whether
      the long-standing proscription against physician-assisted suicide for terminally
      ill patients should be eliminated or changed. In this article we first review the
      history of the centuries-long debate, and repeat the arguments stated for and
      against such a change. We present our opposition to such a change based on the
      adverse consequences which would occur in the patient-doctor relationship, and
      the very likely extension of the practice from only terminally ill patients to
      some who are suffering but not dying, including patients with intractable mental
      suffering. We review the 10-year social experiment with public toleration of
      euthanasia in the Netherlands, and note its considerable expansion beyond the
      clear guidelines. We then discuss why we believe psychiatrists should continue to
      oppose the legalization of physician-assisted suicide. In addition to our concern
      about the extension to assisted-suicide for mental suffering, we point out the
      adverse affect such changes would have on both the psychiatrist's and the
      patient's perception of the role of the therapist in other suicide situations,
      and the difficulty of uncovering a competent patient's motivation for a request
      for such assistance.

PMID- 15719511
TI  - Synthesis of novel poly(ethylene glycol)-based polyurethanes for drug delivery
      systems.

PMID- 15719512
TI  - Injectable amphiphilic hydrogels based on degradable PLA-PEO-PLA triblock
      copolymers: the need to revisit PEG-protein interactions.

PMID- 15719513
TI  - Viability of smooth muscle cells cultured on collagenous scaffolds for tissue
      engineering of blood vessels.

PMID- 15719514
TI  - Free market assertions should not trump ethical reflections.

PMID- 15719515
TI  - Solve the organ shortage: let the bidding begin!
AB  - Commercialization of transplantable human organs is the only sure way to end the
      crisis of their supply. This is best accomplished by implementing a free, non
      profit, nationwide, ultimately global online auction market. It should be
      independent of the current United Network of Organ Sharing (UNOS) system dealing
      solely with altruistic donation, and of governmental, sectarian, academic, and
      other bureaucratic control. The operation of such an auction is described with a
      hypothetical example. An included provision guarantees equity for poor,
      uninsured, and indigent recipients. Money accrued can be substantial, and would
      be disbursed by established formula, with major portions going to donors'
      families and to special funds to be used to bid for the poor and to defray costs
      incurred by them. As the organ shortage eases, bid prices should drop, resulting
      perhaps in eventual altruistic donation. Objections to commericalization based on
      ethics, bodily sanctity, inequity, pecuniary greed, and the slippery slope tocsin
      are nullified by cogent arguments and examples. The current situation has
      worsened despite so-called required request laws, proposed token payments to
      cover funeral expenses for donor families, and extensive media advertising to
      spur altruistic donation. Prohibitive national and state laws must be rescinded
      for the sake of more than 60,000 patients now on lengthening waiting lists. A
      profession committed to saving lives is duty-bound to endorse, help implement,
      and participate in an auction system dedicated to that end.

PMID- 15719516
TI  - Electrospinning collagen and elastin for tissue engineering small diameter blood
      vessels.

PMID- 15719517
TI  - Human rights dynamics of abortion law reform.
AB  - The legal approach to abortion is evolving from criminal prohibition towards
      accommodation as a life-preserving and health-preserving option, particularly in
      light of data on maternal mortality and morbidity. Modern momentum for
      liberalization comes from international adoption of the concept of reproductive
      health, and wider recognition that the resort to safe and dignified healthcare is
      a major human right. Respect for women's reproductive self-determination
      legitimizes abortion as a choice when family planning services have failed, been
      inaccessible, or been denied by rape. Recognition of women's rights of equal
      citizenship with men requires that their choices for self-determination be
      legally respected, not criminalized.

PMID- 15719518
TI  - Properties of gamma-irradiated poly(trimethylene carbonate).

PMID- 15719519
TI  - Some issues of the medico-legal assessment of the severity of the damage to the
      health in jaw fractures.

PMID- 15719520
TI  - Ethics and intellectual disability.
AB  - A shift in accepted practice regarding sharing research led one editor to discuss
      adopting a legal rather than a moral stance to enforce ethical standards.
      Familiar ethical concerns regarding consent and balancing individual rights
      against those of others are considered, alongside lacunae in the field, by
      drawing on virtue ethics. Reappraisals of quality of life, person-centered
      planning and normalization are discussed, concluding that developing ethical
      relationships with people who have intellectual disability takes precedence over
      client competency.

PMID- 15719521
TI  - Ethics of community psychiatry.
AB  - Psychiatric care in the community gives rise to ethical dilemmas which resemble
      those associated with predominantly institutional care. However, there are also
      dilemmas specifically associated with community care, many of which are
      conceptual as well as practical. Papers addressing both conceptual and practical
      ethical dilemmas are reviewed including some papers which deal with the ethical
      issues associated with violence in the community by the mentally ill.

PMID- 15719522
TI  - Research and ethics: leaving exclusion behind.
AB  - Research into mental disorders has continued to stimulate ethical debate during
      the past year. The urgent need for research in this field remains transparent,
      but the need for balance between enabling research and protecting patients
      continues to generate argument. Informed consent has been the subject of earnest
      debate in the United Kingdom, while attempts to protect incapacitated patients in
      the United States have attracted accusations of stifling research. From this
      baseline, a new movement is emerging, where there are few blanket bans or
      endorsements of specific types of research on specific groups of people. Instead,
      the emphasis is switching to patient participation in research and to the process
      of involving people in research projects.

PMID- 15719523
TI  - Introduction of Sherwin S. Desser, recipient of the Clark P. Read Mentor Award.

PMID- 15719524
TI  - Ethics, treatment and consent.
AB  - This article highlights notable developments in consent in psychiatry over the
      last year. In particular, it identifies increasingly sophisticated
      conceptualizations of consent and competence, and discusses advances in the
      process of decision-making and informed consent to non-treatment areas within
      psychiatry.

PMID- 15719525
TI  - Responsibility and education.
AB  - Ethical assumptions of psychiatry training and practice in a postmodern society,
      and of values and their linked beliefs have become important to search for and to
      acquire if a psychiatrist is to work in an informed, safe and helpful manner.
      These educational themes have particularly impacted on mental health services in
      the past 12 months and are reflected in the publications, including several
      editorials, reviewed. It is unsurprising that this literature is not evidence
      based in a restricted sense; but instead the area reviewed is within the field of
      opinion, purpose of regulatory bodies, and the influence of the public through
      user groups and the ballot box.

PMID- 15719526
TI  - Introduction of Lance A. Durden as the Henry Baldwin Ward medalist for 2004.

PMID- 15719527
TI  - Frequency of consultations and general practitioner recognition of psychological
      symptoms.
AB  - BACKGROUND: General practitioners (GPs) are widely reported to 'miss' half of the
      psychological problems present in their patients. AIMS: To describe the
      relationship between frequency of consultations and GP recognition of
      psychological symptoms. DESIGN OF STUDY: Survey of GPs and their patients.
      SETTING: General practices in the southern part of New Zealand's North Island.
      METHOD: Participants were randomly selected GPs (n = 70), and their patients (n =
      3414, of whom a sub-set of 386 form the basis of this study). The main measure
      was the comparison between GP and composite international diagnostic interview
      (CIDI) recognition of psychological problems. RESULTS: Of the GPs selected, 90%
      participated. The CIDI was completed by 70% of selected patients. In patients (n
      = 386) with a CIDI-diagnosed disorder, 63.7% (95% confidence interval [CI] = 53.3
      to 74.1) were considered by the GP to have had psychological symptoms in the last
      year; 40.1% (CI = 31.0 to 49.2) to have had clinically significant psychological
      problems, and 33.8% (CI = 24.9 to 42.6) were given an explicit diagnosis.
      However, in those CIDI-diagnosed patients who had been seen five or more times
      during the previous year, these recognition figures increased to 80.2% (CI = 68.9
      to 91.4), 59.4% (CI = 45.9 to 72.9) and 53.6% (CI = 40.1 to 67.1) respectively,
      and dropped to 28.8% (CI = 13.0 to 44.7), 13.6% (CI = 3.4 to 23.7), and 10.7% (CI
      = 1.4 to 19.9) among patients not consulting during the previous year. GPs often
      differed from the CIDI in their assessment of clinical significance and
      diagnosis. CONCLUSION: GP non-recognition of psychological problems was at a
      problematic level only among patients with little recent contact with the GP.
      Efforts to improve GP recognition of mental disorder may be more effective if
      they target new or infrequent attenders, and encourage patient disclosure of
      psychological issues.

PMID- 15719528
TI  - The National Survey of American Life: a study of racial, ethnic and cultural
      influences on mental disorders and mental health.
AB  - The objectives of the National Survey of American Life (NSAL) are to investigate
      the nature, severity, and impairment of mental disorders among national samples
      of the black and non-Hispanic white (n = 1,006) populations in the US. Special
      emphasis in the study is given to the nature of race and ethnicity within the
      black population by selecting and interviewing national samples of African
      American (N = 3,570), and Afro-Caribbean (N = 1,623) immigrant and second and
      older generation populations. National multi-stage probability methods were used
      in generating the samples and race/ethnic matching of interviewers and
      respondents were used in the largely face-to-face interview, which lasted on
      average 2 hours and 20 minutes. The Diagnostic and Statistical Manual (DSM) IV
      World Mental Health Composite Interview (WHO-CIDI) was used to assess a wide
      range of serious mental disorders, potential risk and resilience factors, and
      help seeking and service use patterns. This paper provides an overview of the
      design of the NSAL, sample selection procedures, recruitment and training of the
      national interviewing team, and some of the special problems faced in
      interviewing ethnically and racially diverse national samples. Unique features of
      sample design, including special screening and listing procedures, interviewer
      training and supervision, and response rate outcomes are described.

PMID- 15719529
TI  - Considering context, place and culture: the National Latino and Asian American
      Study.
AB  - This paper provides a rationale for, and overview of, procedures used to develop
      the National Latino and Asian American Study (NLAAS). The NLAAS is nationally
      representative community household survey that estimates the prevalence of mental
      disorders and rates of mental health service utilization by Latinos and Asian
      Americans in the US. The central aims of the NLAAS are to: 1) describe the
      lifetime and 12-month prevalence of psychiatric disorders and the rates of mental
      health services use for Latino and Asian American populations using nationwide
      representative samples of Latinos and Asian Americans, 2) assess the associations
      among social position, environmental context, and psychosocial factors with the
      prevalence of psychiatric disorders and utilization rates of mental health
      services, and 3) compare the lifetime and 12-month prevalence of psychiatric
      disorders, and utilization of mental health services of Latinos and Asian
      Americans with national representative samples of non-Latino whites (from the
      National Comorbidity Study-Replication) (NCS-R) and African Americans (from the
      National Survey of American Life) (NSAL). This paper presents new concepts and
      methods utilized in the development of the NLAAS to capture and investigate
      ethnic, cultural and environmental considerations that are often ignored in
      mental health research.

PMID- 15719530
TI  - Sample designs and sampling methods for the Collaborative Psychiatric
      Epidemiology Studies (CPES).
AB  - This paper provides an overview of the probability sample designs and sampling
      methods for the Collaborative Psychiatric Epidemiology Studies (CPES): the
      National Comorbidity Survey Replication (NCS-R), the National Study of American
      Life (NSAL) and the National Latino and Asian American Study of Mental Health
      (NLAAS). The multi-stage sample design and respondent selection procedures used
      in these three studies are based on the University of Michigan Survey Research
      Center's National Sample designs and operations. The paper begins with a general
      overview of these designs and procedures and then turns to a more detailed
      discussion of the adaptation of these general methods to the three specific study
      designs. The detailed discussions of the individual study samples focus on design
      characteristics and outcomes that are important to analysts of the CPES data sets
      and to researchers and statisticians who are planning future studies. The paper
      describes how the expected survey cost and error structure for each of these
      surveys influenced the original design of the samples and how actual field
      experience led to changes and adaptations to arrive at the final samples of each
      survey population.

PMID- 15719531
TI  - The development and implementation of the National Comorbidity Survey
      Replication, the National Survey of American Life, and the National Latino and
      Asian American Survey.
AB  - This paper provides an overview of the development and implementation of the
      Collaborative Psychiatric Epidemiology Surveys (CPES): the National Comorbidity
      Survey Replication (NCS-R), the National Survey of American Life (NSAL), and the
      National Latino and Asian American Study (NLAAS). It describes the instrument
      development and testing phases, the development of training and other project
      materials, interviewer recruitment and training activities, and data collection
      procedures and outcomes. The last section offers recommendations for other
      researchers who undertake similar studies and who might benefit from the
      experiences learned in the development and operation of NCS-R, NSAL and NLAAS.

PMID- 15719534
TI  - The tempest of trauma.

PMID- 15719532
TI  - Cultural relevance and equivalence in the NLAAS instrument: integrating etic and
      emic in the development of cross-cultural measures for a psychiatric epidemiology
      and services study of Latinos.
AB  - This paper describes the development, translation and adaptation of measures in
      the National Latino and Asian American Study (NLAAS). We summarize the techniques
      used to attain cultural relevance; semantic, content and technical equivalency;
      and internal consistency of the measures across languages and Latino sub-ethnic
      groups. We also discuss some of the difficulties and thallenges encountered in
      doing this work. The following three main goals are addressed in this paper: (1)
      attaining cultural relevance by formulating the research problem with attention
      to the fundamental cultural and contextual differences of Latinos and Asians as
      compared to the mainstream population; (2) developing cultural equivalence in the
      standardized instruments to be used with these populations; and (3) assessing the
      generalizability of the measures - i.e., that the measures do not fluctuate
      according to culture or translation. We present details of the processes and
      steps used to achieve these three goals in developing measures for the Latino
      population. Additionally, the integration of both the etic and emic perspectives
      in the instrument adaptation model is presented.

PMID- 15719533
TI  - Methodological innovations in the National Survey of American Life.
AB  - This paper provides an overview of the conceptualization and methods used in the
      National Survey of American Life (NSAL). The objectives of the NSAL are to
      investigate the nature, severity, and impairment of mental disorders among
      national samples of the black and non-Hispanic white (n = 1,006) populations in
      the US, including African American (N = 3,570), and Afro-Caribbean (N = 1,623)
      immigrant and second and older generation, populations. National multi-stage
      probability methods were used in generating the samples and race/ethnic matching
      of interviewers and respondents were employed in the largely face-to-face
      interview, lasting on average 2 hours and 20 minutes. Two methodological
      approaches are described for addressing sampling coverage of individuals attached
      to, but not residing in, selected households at the time of the study. The paper
      also describes two approaches used to address concerns about the interpretations
      of standard symptom probe information in assessing serious mental disorders. This
      included a clinical reappraisal study designed to ascertain differences in
      symptom responding and ascertainment of cases (N = 677) in a subset of the same
      NSAL respondents. Finally, an abbreviated, novel method for estimating the
      prevalence of mental disorders in first-degree family members is described and
      the preliminary results from this new approach are reported.

PMID- 15719535
TI  - In the interest of correctness.

PMID- 15719536
TI  - Reinventing the wheel.

PMID- 15719537
TI  - When pucks fly and corn dogs fry.

PMID- 15719538
TI  - No room in the ER.

PMID- 15719539
TI  - The healing touch.

PMID- 15719541
TI  - A net, not a sieve.

PMID- 15719540
TI  - Invisible wounds.

PMID- 15719542
TI  - On the level.

PMID- 15719543
TI  - If disaster strikes.

PMID- 15719544
TI  - Disaster planning in cyberspace.

PMID- 15719545
TI  - Fire and flu.

PMID- 15719546
TI  - Rural Minnesota needs a trauma system.

PMID- 15719547
TI  - Raising the bar for trauma care in Minnesota: proposal for a statewide trauma
      system.
AB  - Minnesota is 1 of 9 states in the nation that have not implemented a formal
      system to coordinate the care that hospitals provide to victims of trauma. Past
      efforts to initiate such a system have floundered in part because they failed to
      consider the unique needs and capabilities of rural hospitals, which often are
      the first providers of care for trauma victims. This article describes a new
      effort to develop a statewide trauma system. The proposed system attempts to
      include all hospitals in the state in a voluntary network of trauma care. Key
      components of the plan include educating staff at small rural hospitals,
      instituting performance improvement programs, and establishing a trauma registry
      that will allow for statewide injury analysis.

PMID- 15719548
TI  - Epidemiology of trauma in Minnesota.
AB  - Injury accounts for more than 2,500 deaths and 300,000 hospital admissions in
      Minnesota each year. Using the 2002 Minnesota hospital discharge database, we
      examined the subset of hospital-treated injuries that received trauma care and
      categorized claims into trauma-related deaths, cases of nonfatal major trauma,
      and other cases that received specialized trauma care. We also examined where
      trauma patients received their care, the leading diagnoses for trauma deaths and
      nonfatal major trauma, and whether a statewide trauma system that would identify
      and equip more hospitals as trauma centers would have significant potential for
      improving trauma care in Minnesota.

PMID- 15719549
TI  - Pediatric trauma--unique considerations in evaluating and treating children.
AB  - In Minnesota, accidental traumatic injury remains the leading cause of death and
      disability among people ages 1 through middle age. Trauma care providers who
      treat children must be aware of fundamental differences between pediatric
      patients and adults. The intent of this article is to provide readers with a
      primer on some of the clinical issues surrounding the anatomy and physiology of
      children, the key aspects of pediatric triage, and current perspectives on early
      treatment of children with traumatic injuries.

PMID- 15719550
TI  - If you should wake up.

PMID- 15719551
TI  - Regulation of cephalosporin biosynthesis.
AB  - The filamentous fungus Acremonium chrysogenum is the natural producer of the beta
      lactam antibiotic cephalosporin C and is as such used worldwide in major
      biotechnical applications. Albeit its profound industrial importance, there is
      still a limited understanding about the molecular mechanisms regulating
      cephalosporin biosynthesis in this fungus. This review focuses on various
      regulatory levels of cephalosporin biosynthesis. In addition to precursor and
      antibiotic biosynthesis, molecular genetic characteristics of cephalosporin
      biosynthesis genes and the knowledge of multiple layers of their regulatory
      expressional control, as well as the function of activators or repressors on
      cephalosporin biosynthesis are jointly being surveyed. Furthermore, this review
      summarizes (i) molecular features, which distinguish strains with different
      production levels and (ii) examples of molecular engineering approaches to A.
      chrysogenum.

PMID- 15719552
TI  - Regulation of penicillin biosynthesis in filamentous fungi.
AB  - The beta-lactam antibiotic penicillin is one of the mainly used antibiotics for
      the therapy of infectious diseases. It is produced as end product by some
      filamentous fungi only, most notably by Aspergillus (Emericella) nidulans and
      Penicillium chrysogenum. The penicillin biosynthesis is catalysed by three
      enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC)
      and aatA (penDE). The genes are organised into a gene cluster. Although the
      production of secondary metabolites as penicillin is not essential for the direct
      survival of the producing organisms, several studies indicated that the
      penicillin biosynthesis genes are controlled by a complex regulatory network,
      e.g. by the ambient pH, carbon source, amino acids, nitrogen etc. A comparison
      with the regulatory mechanisms (regulatory proteins and DNA elements) involved in
      the regulation of genes of primary metabolism in lower eukaryotes is thus of
      great interest. This has already led to the elucidation of new regulatory
      mechanisms. Positively acting regulators have been identified such as the pH
      dependent transcriptional regulator PACC, the CCAAT-binding complex AnCF and seem
      also to be represented by recessive trans-acting mutations of A. nidulans (prgA1,
      prgB1, npeE1) and R chrysogenum (carried by mutants Npe2 and Npe3). In addition,
      repressors like AnBH1 and VeA are involved in the regulation. Furthermore, such
      investigations have contributed to the elucidation of signals leading to the
      production of penicillin and can be expected to have a major impact on rational
      strain improvement programs.

PMID- 15719553
TI  - Novel genes involved in cephalosporin biosynthesis: the three-component
      isopenicillin N epimerase system.
AB  - Cephalosporin is one of the best beta-lactam antibiotics, widely used in the
      treatment of infectious diseases. It is synthesized by Acremonium chrysogenum.
      The levels of cephalosporin produced by the improved strains obtained by
      classical mutation and selection procedures are still low compared to the
      penicillin titers obtained from the high-producing Penicillium chrysogenum
      strains. Most of the genes encoding the cephalosporin biosynthesis enzymes have
      been cloned, and some improvement of cephalosporin production has been achieved
      by removing bottlenecks in the pathway. One of the poorly-known steps involved in
      cephalosporin biosynthesis is the conversion of isopenicillin N into penicillin N
      catalyzed by the isopenicillin N epimerase system. This epimerization reaction is
      catalyzed by a two-component protein system encoded by the cefD1 and cefD2 genes
      that correspond, respectively, to an isopenicillinyl-CoA ligase and an
      isopenicillinyl-CoA epimerase. Comparative analysis of those proteins with others
      in the databanks provide evidence indicating that they are related to enzymes
      catalyzing the catabolism of toxic metabolites in animals. There are several
      biochemical mechanisms, reviewed in this article, for the biosynthesis of D-amino
      acids in secondary metabolites. The conversion of isopenicillin N to penicillin N
      in cephamycin-producing bacteria is mediated by a classical pyridoxal phosphate
      dependent epimerase that is clearly different from the epimerization system
      existing in Acremonium chrysogenum. Modification of gene expression by directed
      manipulation of the cefD1-cefD2 bidirectional promoter region is a promising
      strategy for improving cephalosporin production. Improving our knowledge of the
      mechanism of epimerization systems is important if we wish to understand how
      microorganisms synthesize the high number of rare D-amino acids that are
      responsible, to a large extent, for the biological activities of many different
      secondary metabolites.

PMID- 15719554
TI  - Compartmentalization and transport in beta-lactam antibiotics biosynthesis.
AB  - Classical strain improvement of beta-lactam producing organisms by random
      mutagenesis has been a powerful tool during the last century. Current insights in
      the biochemistry and genetics of beta-lactam production, in particular in the
      filamentous fungus Penicillium chrysogenum, however, make a more directed and
      rational approach of metabolic pathway engineering possible. Besides the need for
      efficient genetic methods, a thorough understanding is needed of the metabolic
      fluxes in primary, intermediary and secondary metabolism. Controlling metabolic
      fluxes can be achieved by adjusting enzyme activities and metabolite levels in
      such a way that the main flow is directed towards the desired product. In
      addition, compartmentalization of specific parts of the beta-lactam biosynthesis
      pathways provides a way to control this pathway by clustering enzymes with their
      substrates inside specific membrane bound structures sequestered from the
      cytosol. This compartmentalization also requires specific membrane transport
      steps of which the details are currently uncovered.

PMID- 15719555
TI  - Control of fluxes towards antibiotics and the role of primary metabolism in
      production of antibiotics.
AB  - Yield improvements in antibiotic-producing strains have classically been obtained
      through random mutagenesis and screening. An attractive alternative to this
      strategy is the rational design of producer strains via metabolic engineering, an
      approach that offers the possibility to increase yields while avoiding the
      problems of by-product formation and altered morphological properties, which
      frequently arise in mutagenized strains. An important aspect in the design of
      strains with improved yields by metabolic engineering is the identification of
      rate-controlling enzymatic reactions in the metabolic network. Here we describe
      and discuss available methods for identification of these steps, both in
      antibiotic biosynthesis pathways and in the primary metabolism, which serves as
      the supplier of precursors and cofactors for the secondary metabolism. Finally,
      the importance of precursor and cofactor supply from primary metabolism in the
      biosynthesis of different types of antibiotics is discussed and recent
      developments in metabolic engineering towards increased product yields in
      antibiotic producing strains are reviewed.

PMID- 15719556
TI  - Industrial enzymatic production of cephalosporin-based beta-lactams.
AB  - Cephalosporins are chemically closely related to penicillins both work by
      inhibiting the cell wall synthesis of bacteria. The first generation
      cephalosporins entered the market in 1964. Second and third generation
      cephalosporins were subsequently developed that were more powerful than the
      original products. Fourth generation cephalosporins are now reaching the market.
      Each newer generation of cephalosporins has greater Gram-negative antimicrobial
      properties than the preceding generation. Conversely, the 'older' generations of
      cephalosporins have greater Gram-positive (Staphylococcus and Streptococcus)
      coverage than the 'newer' generations. Frequency of dosing decreases and
      palatability generally improve with increasing generations. The advent of fourth
      generation cephalosporins with the launch of cefepime extended the spectrum
      against Gram-positive organisms without a significant loss of activity towards
      Gram-negative bacteria. Its greater stability to beta-lactamases increases its
      efficacy against drug-resistant bacteria. In this review we present the current
      situation of this mature market. In addition, we present the current state of the
      technologies employed for the production of cephalosporins, focusing on the new
      and environmentally safer 'green' routes to the products. Starting with the
      fermentation and purification of CPC, enzymatic conversion in conjunction with
      aqueous chemistry will lead to some key intermediates such as 7-ACA, TDA and TTA,
      which then can be converted into the active pharmaceutical ingredient (API),
      again applying biocatalytic technologies and aqueous chemistry. Examples for the
      costing of selected products are provided as well.

PMID- 15719557
TI  - Biochemistry and general genetics of nonribosomal peptide synthetases in fungi.
AB  - Peptides like penicillin or cyclosporin are nonribosomally synthesised by large
      multifunctional enzymes. Peptide synthetase genes are coexpressed with other
      biosynthesis genes organised in clusters. Such clusters are common in fungal
      genomes, and the respective products are thought to be advantageous though not
      essential for survival. The biochemistry of the sequential polymerisation
      reactions is reviewed, including multienzyme organization, amino acid activation
      and modification reactions.

PMID- 15719558
TI  - [Tuberculosis among Danish men].

PMID- 15719559
TI  - [How should risk be reported?].

PMID- 15719560
TI  - [Diphosphonates in solid malignant tumors].

PMID- 15719561
TI  - [Magnetic resonance imaging in neuropediatrics].

PMID- 15719562
TI  - [Lipidemia, food and exercise].

PMID- 15719563
TI  - [Alarming tendency in the transmission of tuberculosis among Danish men].

PMID- 15719564
TI  - [Do refugees carry diseases?].

PMID- 15719565
TI  - [Antibiotic treatment in four departments of a university hospital. A descriptive
      period prevalence study].

PMID- 15719566
TI  - [Local recurrence and survival after mesorectal excision for rectal cancer-
      secondary publication].

PMID- 15719567
TI  - [Optimized use of Emla cream in children--secondary publication. A randomized,
      prospective, controlled comparison of two application regimes].

PMID- 15719568
TI  - [Extreme anemia caused by a bleeding gastrointestinal stromal tumor].

PMID- 15719570
TI  - [Spontaneous ovarian hyperstimulation syndrome in a normal singleton pregnancy].

PMID- 15719569
TI  - [Hypernatremia and neurological complications in rotavirus gastroenteritis].

PMID- 15719571
TI  - [Treatment of cirrhotic complications with human serum albumin].

PMID- 15719572
TI  - [Young physicians must have contact with psychiatry].

PMID- 15719573
TI  - [Psychiatry--yes, please! District psychiatry--yes, please!].

PMID- 15719574
TI  - Importation reports spur more debate about drug price.

PMID- 15719575
TI  - Safety advisory group gets mixed marks from members.

PMID- 15719576
TI  - Nation is unprepared for bioterrorism threat, study finds.

PMID- 15719577
TI  - Technology hasn't eliminated medication errors yet, USP reports.

PMID- 15719578
TI  - New drugs and dosage forms.

PMID- 15719579
TI  - Ohio guidelines for advanced-practice hospital rotations for pharmacy students.

PMID- 15719580
TI  - Reform of U.S. vaccine management.

PMID- 15719581
TI  - Direct thrombin inhibitors in heparin-induced thrombocytopenia.

PMID- 15719582
TI  - Developing new practitioners' leadership potential.

PMID- 15719583
TI  - Unresolved issues in pharmacy.

PMID- 15719584
TI  - Adjuvant use of aromatase inhibitors in postmenopausal women with breast cancer.
AB  - PURPOSE: Emerging data from clinical trials on the use of aromatase inhibitors in
      the management of early-stage, hormone-dependent breast cancer in postmenopausal
      women are reviewed. SUMMARY: Aromatase is the enzyme responsible for the
      conversion of androgens to estrogens and the only source of estrogens in
      postmenopausal women. Clinical trials using aromatase inhibitors in the adjuvant
      treatment of postmenopausal women with breast cancer are few but significant
      because of their comparative design with tamoxifen given for five years, long
      regarded as the gold standard for breast cancer treatment. Data from the
      Anastrozole, Tamoxifen and Combination trial, the MA-17 trial (letrozole compared
      with placebo), the Italian Tamoxifen Arimidex trial (anastrozole following
      tamoxifen), and the Intergroup Exemestane Study have shown promising efficacy and
      safety in the use of these agents. While the optimal aromatase inhibitor for use
      in the adjuvant setting has not been elucidated, current evidence-based
      recommendations include using (1) anastrozole as the first adjuvant therapy for
      five years, (2) tamoxifen for two to three years, then exemestane or anastrozole
      for the remainder of the five years, and (3) tamoxifen for five years, then
      letrozole for another five years. CONCLUSION: While their impact on survival has
      not been determined, aromatase inhibitors are slowly changing the management of
      early-stage, hormone-dependent breast cancer in postmenopausal women because of
      improved disease-free survival rates. Their ultimate role in therapy is unknown,
      but educating patients about the potential risks and benefits will allow them to
      make informed decisions regarding these data and their breast cancer care.

PMID- 15719585
TI  - ASHP survey of ambulatory care pharmacy practice in health systems--2004.
AB  - PURPOSE: The characteristics of and trends in pharmacy practice in ambulatory
      care settings across the United States were studied. METHODS: A 2004 national
      survey of the ambulatory care responsibilities of pharmacists across a spectrum
      of organizational types (community hospitals, county facilities, Indian Health
      Services facilities, Veterans Affairs (VA) facilities, teaching institutions,
      integrated health networks, military facilities, and health maintenance
      organizations) was conducted and related to organizational features that could
      promote pharmacist participation. RESULTS: From 1672 deliverable Web-based
      surveys, 233 organizations reported at least some pharmacist involvement in
      ambulatory activities, while 475 reported none. Over half of the 228
      organizations with some pharmacist involvement reported pharmacists tracking
      adverse drug reactions (67%), providing written (53%) or oral (52%) information
      with new prescriptions, and conducting medication management programs (51%). Some
      85% reported having at least one clinic with pharmacist involvement. Clinics for
      anticoagulation services (36%) and oncology services (28%) were most prevalent,
      followed by primary care or family practice clinics (23%) and diabetes clinics
      (21%). New survey items found a high prevalence of pharmacist involvement in
      emergency preparedness programs (90%), medication management services in complex
      medication situations (63%), and using evidence-based practice guidelines (60%).
      Of nine enabling factors (factors potentially promoting pharmacist involvement)
      investigated, participation on multidisciplinary teams and having collaborative
      practice agreements were significantly associated with pharmacist participation
      in at least one ambulatory care activity. Having at last one ambulatory care
      staff pharmacist with advanced training, having at least one residency program,
      and having collaborative practice agreements were significantly associated with
      pharmacist participation in at least one clinic or program. Pharmacist
      participation in ambulatory care activities was not equally distributed across
      different types of organizations, and VA facilities were notable for the amount
      and extent of participation. CONCLUSION: Pharmacists' roles and responsibilities
      in ambulatory care appear to continue to evolve, with VA facilities leading the
      way.

PMID- 15719586
TI  - Using a medium-fill simulation to evaluate the microbial contamination rate for
      USP medium-risk-level compounding.
AB  - PURPOSE: The estimated microbial contamination rate for complex, multiple-step,
      medium-risk-level compounding was studied. METHODS: The results of evaluations of
      the aseptic technique of pharmacists and technicians in compounding complex USP
      medium-risk-level sterile preparations were compiled to estimate the microbial
      contamination rate. The testing took place in 2002 and 2003 at a single
      institution and involved reconstitution of sterile dry growth medium and a series
      of complicated transfers of the medium from vials and ampuls to intravenous bags.
      The bags were incubated at 25-35 degrees C for 14 days and observed for microbial
      growth. RESULTS: Of 539 evaluations, 28 (5.2%) resulted in preparations that
      yielded microbial growth. Pharmacists' compounding resulted in a slightly lower
      contamination rate (4.4%) than that of technicians (6.2%). Inadvertent touch
      contamination may have been the principal source of the contamination.
      CONCLUSION: . A two-year series of 539 evaluations of the aseptic technique of
      pharmacists and technicians conducted with sterile growth medium and designed to
      simulate the compounding of USP medium-risk-level sterile preparations yielded an
      overall contamination rate of 5.2%.

PMID- 15719587
TI  - Stability of roxatidine acetate in parenteral nutrient solutions containing
      different amino acid formulations.

PMID- 15719589
TI  - Moving toward whole-genome analysis: a technology perspective.
AB  - PURPOSE: New, highly efficient technologies used in genomic analysis are
      described, and their implications for health care are discussed. SUMMARY: The
      availability of the human genome sequence, in confluence with the ability to
      affordably package it for analysis, is opening new frontiers in biomedical
      research. On the horizon, personalized medicine--driven by molecular
      characterization of disease, genetic analysis of the patient, and information
      technologies designed to enable health care professionals to leverage these tools
      -promises to fundamentally transform health care. New genetics technologies, such
      as high-density microarrays, will fuel this research by providing researchers
      with the ability to comprehensively access the human genome in all its
      complexity. Some of the most promising areas for application of genetic
      information are those where society's current needs are greatest: complex, common
      disorders, such as cancer and cardiovascular disease; drug interactions;
      inherited genetic disorders that afflict children; and late-onset conditions for
      which no cure currently exists. The barriers to using genetic information widely
      in health care are in many cases not technological or economic, but social and
      political. CONCLUSION: New technology enables efficient, large-scale analysis of
      the whole genome, genetic variations, and gene expression. Genomic analysis has
      profound clinical, economic, and social implications for health care.

PMID- 15719588
TI  - Concomitant use of nesiritide and milrinone in decompensated congestive heart
      failure.

PMID- 15719590
TI  - Defining "legitimate medical purpose".

PMID- 15719591
TI  - Calculating aluminum content in total parenteral nutrition admixtures.

PMID- 15719592
TI  - Aluminum exposure through parenteral nutrition formulations: mathematical versus
      clinical relevance.

PMID- 15719593
TI  - Inhaled opioids for the treatment of dyspnea.

PMID- 15719594
TI  - Survey of hospital pharmacy practice in Flemish-speaking Belgium.

PMID- 15719595
TI  - Aromatase inhibitors in advanced breast cancer.
AB  - The third-generation aromatase inhibitors suppress whole-body estrogen production
      in postmenopausal women with high specificity and potency. In women with hormone
      sensitive breast cancer, three of these agents, letrozole, anastrozole, and
      exemestane, provide an important alternative endocrine therapy to the
      antiestrogen tamoxifen, which blocks estrogen activation of the estrogen
      receptor. For treatment of advanced or metastatic breast cancer that has
      progressed on first-line tamoxifen, all three agents are active. On that basis,
      they have each been compared with tamoxifen as first-line therapy of advanced
      breast cancer, in phase III trials. Letrozole was significantly superior to
      tamoxifen in the primary end point, median time to progression, as well as in
      response rate and clinical benefit rate, and treatment was well tolerated.
      Although there was no significant difference in median overall survival, an
      advantage seen with letrozole for the first 2 years may have been lost because of
      crossover to the alternate agent at disease progression. Anastrozole was
      evaluated in two separate trials designed for combined analysis. Overall,
      anastrozole was at least equivalent to tamoxifen in activity, but clearly
      superior only for median time to progression in the subgroup of patients with
      hormone receptor-positive disease. Treatment was generally as well tolerated as
      tamoxifen. In an early report, exemestane was significantly better than tamoxifen
      in response rate and median time to progression, with overall survival data not
      yet available. To date, letrozole appears to be the most effective aromatase
      inhibitor in the first-line advanced breast cancer setting.

PMID- 15719596
TI  - Aromatase inhibitors in early breast cancer therapy.
AB  - Third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane,
      are active and well tolerated in postmenopausal patients with hormone-sensitive
      advanced or metastatic breast cancer, as either first- or second-line therapy.
      These agents are being investigated as neoadjuvant therapy of locally advanced
      breast cancer and as adjuvant therapy of early breast cancer. In a large
      neoadjuvant study, letrozole resulted in significantly more responses than
      tamoxifen, with significantly more patients becoming eligible for breast
      conserving surgery. Greater letrozole responses were associated with high and low
      levels of estrogen receptor expression and with coexpression of ErbB-1 and/or
      ErbB-2. Neoadjuvant anastrozole, in two studies, was also significantly superior
      to tamoxifen in rendering patients eligible for breast-conserving surgery. In the
      adjuvant setting, the Arimidex, Tamoxifen Alone or in Combination trial compared
      5 years of anastrozole versus tamoxifen versus the combination. At 47 months'
      median follow-up, disease-free survival was significantly improved with
      anastrozole compared with the other arms. In the Intergroup Exemestane Study,
      switching to exemestane after 2 to 3 years of tamoxifen significantly improved
      disease-free survival compared with remaining on tamoxifen for 5 years. The MA.17
      trial evaluated switching to letrozole versus placebo following 5 years of
      adjuvant tamoxifen, and letrozole was significantly superior to placebo in
      disease-free survival. While all three aromatase inhibitors as adjuvant therapy
      were well tolerated, long-term effects on bone health and lipids are being
      monitored. Ongoing trials will better define the optimum use of aromatase
      inhibitors as adjuvant therapy.

PMID- 15719597
TI  - Changing clinical practice: extending the benefits of adjuvant endocrine therapy
      in breast cancer.
AB  - Five years of tamoxifen is standard adjuvant therapy for hormone-sensitive early
      breast cancer, but women remain at appreciable risk of recurrence for many years
      following that therapy, and further tamoxifen does not appear to be beneficial.
      Trial MA.17 was designed to determine whether, following 5 years of tamoxifen,
      switching disease-free postmenopausal women to the aromatase inhibitor letrozole
      for 5 years improved disease-free survival compared with switching to placebo.
      The rationale was that as residual cancer cells become tamoxifen resistant, their
      growth may be stimulated by the minor agonist effect of tamoxifen as well as by
      very low estrogen concentrations. Those cells might be particularly sensitive to
      tamoxifen withdrawal coupled with treatment with a potent suppressor of estrogen
      synthesis. At the first planned interim analysis of MA.17, "extended adjuvant"
      letrozole significantly improved estimated 4-year disease-free survival overall
      (93% for letrozole v 87% for placebo; P < .001), irrespective of nodal status.
      Recurrences were reduced to a comparable extent for all included events,
      locoregional and distant recurrences (53% and 38%, respectively) and new primary
      cancers in the contralateral breast (46%). Breast cancer deaths were reduced by
      47% with letrozole versus placebo. Letrozole treatment was well tolerated, with
      most adverse events mild and expected as symptoms of estrogen deprivation. This
      is the first demonstration that extended adjuvant therapy after standard
      tamoxifen in postmenopausal women with early breast cancer has a clinically
      significant impact on outcome.

PMID- 15719598
TI  - Optimizing bisphosphonate therapy in patients with breast cancer on endocrine
      therapy.
AB  - Deterioration of bone health is a major concern during progression and treatment
      of patients with breast cancer, especially in postmenopausal women. Disease- and
      treatment-associated skeletal-related events include fractures, spinal
      compression, bone pain, and hypercalcemia of malignancy. Bisphosphonates, which
      inhibit osteoclastic bone resorption, are important new agents in the management
      of skeletal-related events, and their impact on breast cancer-related bone
      metastases and on bone loss during long-term estrogen deprivation therapies such
      as aromatase inhibitors is reviewed. Intravenous pamidronate has become the
      standard bisphosphonate to reduce or delay skeletal complications of advanced
      breast cancer bone metastases, but the more potent agent, zoledronic acid,
      appears to be at least as effective. Another agent, ibandronate, is also active
      but has not been investigated in comparison with the other intravenous
      bisphosphonates. Zoledronic acid is the most convenient to administer, requiring
      only a short infusion. The effects of bisphosphonates on bone health in women
      with early breast cancer are also being investigated. A single yearly infusion of
      zoledronic acid has been shown to significantly increase bone mineral density in
      osteoporotic postmenopausal women and to reduce biochemical markers of bone
      turnover. The possibility of such treatment-reversing aromatase inhibitor
      associated bone loss during adjuvant therapy of breast cancer is being evaluated
      in a trial of letrozole, with zoledronic acid added initially or after the onset
      of bone loss or fracture.

PMID- 15719599
TI  - Aromatase inhibitors in the management of early breast cancer: optimizing the
      clinical benefit.
AB  - Several adjuvant trials evaluating aromatase inhibitors in postmenopausal women
      with early breast cancer have shown significant improvement upon, or extension of
      the efficacy benefits of, standard therapy with tamoxifen, and treatments were
      generally well tolerated. Disease-free survival was significantly improved by:
      anastrozole versus tamoxifen for 5 years of adjuvant therapy, in the Arimidex,
      Tamoxifen Alone or in Combination trial; switching to exemestane after 2 to 3
      years of tamoxifen, compared with remaining on tamoxifen for 5 years, in the
      Intergroup Exemestane Study; and switching to letrozole (v placebo) for 5 years
      after 5 years of tamoxifen, in the extended adjuvant trial, MA.17. Further
      analyses of these trials, and data from ongoing trials, will address how to
      optimally use aromatase inhibitors in the adjuvant breast cancer setting: whether
      these agents should be used in place of, or sequenced with, tamoxifen; what is
      the best order of sequencing, before or after tamoxifen, and when is the best
      time to switch; what the long-term safety issues are associated with aromatase
      inhibitor treatment; and how toxicities can be effectively managed.

PMID- 15719600
TI  - Emerging ethical issues in nephrology nursing--part II.

PMID- 15719601
TI  - Cultural perspectives in caring for Chinese renal patients.
AB  - The meaning of the human body, concept of health and illness, beliefs in diet,
      languages, and family structure all have impact on the planning of nursing
      interventions in caring for patients. This article focuses on the impact of the
      above variables on Chinese patients who have renal disease. Suggestions are given
      in caring for this particular group of Chinese patients.

PMID- 15719602
TI  - Moving beyond the walls of tertiary care centres to promote renal health in
      ethnoculturally diverse communities: food for thought.
AB  - End stage renal disease (ESRD) has a profound impact on the quality of life and
      survival of a growing number of Canadians. Although individuals from various
      cultural and ethnic groups are represented in the ESRD population receiving renal
      replacement therapy, there is data indicating that certain groups are at
      increased risk of developing renal failure. The underlying reason for this is not
      entirely clear, but an interaction between genetic factors, environmental
      influences and socioeconomic status has been suggested. In Canada and other
      industrialized countries, common causes of ESRD include diabetes and
      hypertension, both of which are known to be responsive to lifestyle modification
      and preventative interventions. Treatments for these conditions are costly, both
      to the individual and society. One approach to reducing the social and economic
      burden of organ damage may be to create partnerships between multidisciplinary
      tertiary care teams and community groups interested in health promotion. A
      liaison between specialists, general practitioners, health promoters with the
      knowledge of delivering culturally based education to groups, and lay people in
      the community may be an effective means to reducing the burden of ESRD on certain
      ethnic groups in Canada and other Western countries.

PMID- 15719603
TI  - Pregnancy in a hemodialysis patient with an ethical/cultural challenge.
AB  - Each year, one in 200 women of child-bearing age conceive while on dialysis. Of
      those pregnancies not electively terminated, 46% result in a surviving infant.
      Late pregnancy losses are common with 25% ending in second trimester spontaneous
      abortion, stillbirth or neonatal death (Hou & Firanek, 1998). Despite these
      alarming statistics, there has been an increase in the number of successful
      pregnancies reported in the literature (Bagon et al., 1998; Romao et al., 1998).
      This case study presentation will allow readers to appreciate both clinical
      challenges and ethical issues associated with a pregnant, hemodialysis-dependent
      woman. Despite being given information about the risks of pregnancy while on
      dialysis, Mrs. T. was determined to have a second child (she has a two-year-old
      son). Her strong religious beliefs led her to believe that Allah would protect
      her and her child from harm. This created an ethical conflict with many members
      of the interdisciplinary health care team, who were of the opinion that a
      pregnancy would be detrimental to Mrs. T's health. Five months after initiation
      of hemodialysis, Mrs. T. did become pregnant. The unique nature of an Arabic
      speaking Muslim woman who was pregnant and on dialysis provided an opportunity
      for the health care team to become more familiar with cultural and ethical issues
      that impacted greatly on her care. At 36 weeks, Mrs. T. delivered a healthy 2362
      gram (5.1 lb.) baby girl with an apgar score of four and eight.

PMID- 15719605
TI  - Nephrology and the Internet.

PMID- 15719604
TI  - The impact of cultural values on patient education for the elderly.
AB  - Little literature has examined the interaction of culture and patient education
      with specific reference to the elderly. It is necessary for nurses to develop a
      respectful understanding of their patient's culture in order to provide
      meaningful and relevant patient education. Understanding of cultural differences
      is especially important when educating elderly immigrants, as many elderly retain
      significant aspects of their native cultural traditions and may be slower to
      acculturate to Western cultural values. This paper will outline a number of
      assessment parameters and educational strategies necessary for nurses to begin to
      provide culturally sensitive patient education for elderly patients within the
      nephrology setting.

PMID- 15719606
TI  - Prevalence of cytomegalovirus (CMV) infection among neonatal intensive care unit
      (NICU) and healthcare workers.
AB  - CMV is the most common cause of congenital and perinatal infection, most
      infections are asymptomatic at birth but later on develop handicaps, mainly
      neurological disturbances. The aim of the present work is to study the prevalence
      of CMV infection in NICU, to detect possible nosocomial transmission of CMV
      infection and determine possible risk factors for neonatal CMV infection. This
      study was carried on 175 neonates in NICU and 19 employees in the same unit. All
      members of the study were investigated for serum CMV-IgG and IgM by ELISA and CMV
      - DNA by PCR. The overall prevalence of CMV was 12.57%, 10 (5.71%) had congenital
      infection, while 12 cases (6.86%) had perinatal infection. In neonates with
      congenital CMV infection, the prevalence of breast milk feeding, congenital
      anomalies and blood transfusion were 80%, 30% and 60%, respectively. In neonates
      with perinatal CMV infection the prevalence of breast milk feeding, congenital
      anomalies and blood transfusion were 75%, 16.67% and 50%, respectively. On the
      other hand from the 19 employees, 2 (10.53%) were CMV-DNA positive by PCR, none
      of them was CMV-lgM positive and all of them were CMV-IgG positive. The risk
      factors related to CMV infection among neonates in NICU were, low birth weight,
      congenital anomalies and breast milk feeding, while CMV infection among employee
      was related to blood transfusion and employment period. In our results there was
      no statistical correlation between neonates in NICU and employee in the same
      unit. CMV infections are of more prevalence in premature and low birth weight
      neonates in NICU. No evidence of nosocomial CMV transmission to employee in NICU.

PMID- 15719607
TI  - Increased circulating FcepsilonRII-bearing B-lymphocytes and serum levels of IL-4
      in non-autoreactive chronic idiopathic urticaria.
AB  - The exact pathophysiology of chronic idiopathic urticaria (CIU) is not well
      understood. The concept of autoreactivity has evolved to explain the disease in
      up to 50% of cases, while the search for other mechanisms is still needed to
      explain the disease, at least among the remaining subpopulation of non
      autoreactive CIU. Therefore, we thought to investigate some aspects of the IgE
      dependent, lymphocyte-mediated late-phase response (LPR) of anaphylaxis. We
      searched for percentages of FcepsilonRII-bearing (CD23+) B and T lymphocytes and
      correlated this with total IgE serum levels, IL-4 serum levels and the disease
      severity scores. Twenty-five patients with non-autoreactive CIU and ten healthy
      control subjects participated in this study. CD23+ B- and T-cells were assessed
      by flow cytometry, total IgE serum levels were estimated by enzyme linked
      fluorescent assay (ELFA), IL-4 serum levels were estimated by Enzyme Amplified
      Sensitivity Immunoassay (EASIA), while disease severity was determined by a daily
      self-assessment urticaria activity and itching score. Our results showed that the
      mean values for percentages of CD23+ B-cells (6.7 +/- 2.3%), total IgE serum
      levels (139.6 +/- 103.9 microg/dl) and IL-4 serum levels (18.3 +/- 14.7 ng/ml)
      for patients were statistically significant (p = 0.002, 0.013 and 0.008,
      respectively), when compared with the corresponding values for controls (4.0 +/-
      1.7%, 51.5 +/- 25.1 microg/dl, and 5.1 +/- 4.1 ng/ml, respectively), while the
      difference between the mean percentage of CD23+ T-cells for patients (2.8 +/- 2%)
      and that for controls (2.1 +/- 0.6%) was non-significant (p = 0.267). Strong
      positive correlations were detected between percentages of CD23+ B-cells and
      severity scores (r = 0.678, p = 0.0001), total IgE serum levels (r = 0.756, p =
      0.0001) and IL-4 serum levels (r = 0.709, p = 0.0001), while no correlation was
      detected between CD23+ B-cells and CD23+ T-cells (r= 0.188, p= 0.368). It is
      concluded, that CD23+ B-cells, regulated by IL-4, may contribute in the
      pathogenesis of non-autoreactive CIU, by producing high levels of IgE and
      possibly lymphokines, while CD23+ T-cells may be involved in early antigen
      recognition. This may have a future therapeutic ramification in this distinct
      subset of CIU by targeting low-affinity IgE receptors.

PMID- 15719608
TI  - Proinflammatory cytokines (IL-12 and IL-18) in immune rheumatic diseases:
      relation with disease activity and autoantibodies production.
AB  - Interleukin-18 (IL-18) and its inducer IL-12 have multiple biological activities
      that are important in generating Th1 responses and inflammatory tissue damage. We
      investigated serum concentration of the novel proinflammatory Th1 cytokine; IL
      18, and its inducer IL-12 in patients with immune rheumatic diseases. Group I
      comprised32 patients of systemic lupus erythmatosus (SLE), Group II comprised 36
      patients of rheumatoid arthritis (RA). Group III comprised 9 patients (2 patients
      of Behcet, 2 patients of Dermatomyositis, 2 patients of Sicca syndrome, one
      patient of Scleroderma, and 2 patients of Mixed connective tissue disease). Group
      IV is a control group consists of 21 sex and age matched healthy subjects and
      correlated their levels with autoantibody concentration (ANA and ds-DNA),
      clinical grades and SLE disease activity index (SLEDAI). Serum IL-18, IL-12, ANA
      and ds-DNA were measured by enzyme immuno sorbent assay. IL-18, IL-12 and ANA
      were significantly higher in the three studied groups than in the control group
      (IL-18; P < 0.001 in the three groups, IL-12; P = 0.019, P = 0.002, and P =
      0.006, and ANA; P < 0.001, P = 0.002,and P = 0.006, respectively).ds-DNA was
      significantly higher in SLE patients than in control group (P < 0.001). There
      were significant positive correlations between; A) levels of IL-18,and both ANA
      and ds-DNA in SLE patient (r = 0.41,P = 0.001, r = 0.58 and P=0.001
      respectively); and B) IL-18 and ANA in both RA and group III patients (r = 0.32,
      P = 0.005, r = 0.61and P = 0.022 respectively). Also, there were significant
      positive correlation between the levels of IL-18 and clinical grades of the three
      groups (r = 0.60,P = 0.001, r = 0.79,P = 0.001, r = 0.78 and P= 0.001
      respectively). In SLE patients , IL-18 concentration shows significant positive
      correlation with SLEDAI score (r = 0.76, P = 0.001). In conclusion, the elevation
      of proinflammatory cytokines (IL-18 and IL-12 ) may trigger the inflammatory
      process in immune rheumatic diseases and IL-18 is correlated with disease
      activity

PMID- 15719609
TI  - Implication of intercellular adhesion molecule-1 (ICAM-1) and serum N(G)-hydroxy
      L-arginine (L-NHA) in the pathogenesis of systemic sclerosis.
AB  - In a trial to throw light on the implication of intercellular adhesion molecule-1
      (ICAM-1) and N(G)-hydroxy-L-arginine (L-NHA) in the pathogenesis of systemic
      sclerosis or Scleroderma, (SSc), their serum levels were estimated in twenty SSc
      patients using ELISA and high performance liquid chromatography respectively. In
      situ "local" expression of ICAM-1 in lesional skin of these patients was also
      assessed using biotinstreptavidin amplified detection system. Patients were
      divided into 3 groups according to the cutaneous extension of sclerosis (Grades
      I; II & III). A significant (P < 0.001) difference was found between patients (n
      = 20) and controls (n = 10) regarding soluble ICAM-1 (s ICAM-1) and L-NHA levels.
      Among patients, a significant difference (P < 0.001, 0.05 respectively) in sICAM
      1 & L-NHA serum levels was found between patients who had musculoskeletal
      manifestations and those who had not. A significant (P < 0.001) difference in L
      NHA level was found between patients with grade I, II, III. Among patients, there
      was a negative correlation (r = -0.413) between serum sICAM-1 and the duration of
      the disease, and a positive correlation (r = +0.514) between sICAM-1 and L-NHA
      serum levels. 4 patients (23.6%) showed mild immunostaining, 8 patients (47%)
      showed moderate staining, and 5 patients (29.4%) showed intense staining, while
      control specimens showed negative immunostaining. In conclusion, ICAM-1 and serum
      L-NHA are probably implicated in the pathogenesis of SSc. Elevated sICAM-1 and L
      NHA serum could be used as a quantitative marker of tissue sclerosis, allowing
      better follow up of patients.

PMID- 15719610
TI  - Immunological studies on mice vaccinated with irradiated cercaria and IL-12
      against Schistosoma mansoni infection.
AB  - Protective immunity against Schistosoma mansoni infection correlates with
      increased levels of IgE and blood eosinophilia which are considered as markers of
      anti-parasitic cell-mediated immunity. IL-5 participates as well in the induction
      and regulation of IgE and eosinophilia, consequently in the development of
      acquired immunity. Swiss Webster female mice were subcutaneously injected with
      either 50 microg of gamma-irradiated cercarial homogenate (400 Gy) twice weekly
      for three weeks alone or plus a single dose of IL-12 (0.8 ng/Kg). The efficiency
      of immunization regimens were assessed 45 days post infection with 100 live
      cercariae/mouse by the number of worm burden, ova count, production of IL-5,
      eosinophils, and IgE levels in the vaccinated groups compared with the non
      immunized group. The results demonstrated a significant reduction of ova count in
      the livers of vaccinated groups (57.19 and 40.13%) and worm couples compared with
      the non -immunized group. Furthermore, a decrease of IL-5 level as well as
      eosinopenia was recorded in both vaccinated groups. Scanning electron microscope
      (SEM) of adult worms recovered from the immunized groups revealed marked damage
      on the tegumental surface in males rather than females as well as constrictions
      and intensive corrugation of intertubercles.

PMID- 15719611
TI  - Laminarin enhanced immunological disorders of septicimeric albino rats infected
      with Aeromonas hydrophila.
AB  - Aeromonas hydrophila is increasingly recognized as a pathogen of man that gives
      rise to both intestinal and extraintestinal infection. This study examined the
      effect of one the immunostimulants; fungal cell-wall beta-1, 3-D-glucan
      (Laminarin) on the immune response to Aeromonas hydrophila in albino rats.
      Intraperitoneal injection of 0.2 ml of 1% laminarin (15 mg/100 g b.wt) stimulated
      humoral immunity. On the ninth day, after application of laminarin in vivo, a
      statistically higher value of total Ig (p < 0.05) was observed. At the same time,
      serum total immunoglobulins (25.5 +/- 2) g/L in bacterial groups were
      significantly higher (p < 0.05), compared to the control group (17 +/- 2) g/L.
      For Aeromonas infected group, all Ig classes showed increase statistically
      significant (p < 0.05). On the other hand laminarin groups exhibited reduced
      values of Ig subclasses but still higher than control values. This was reported
      for all time period. Rats were divided into 3 equal groups designated, Aeromonas
      infected, Laminarin-treated and control groups. Infection was carrid out by
      intraperitoneal injection of 2 x 10(6) bacteria daily for 6 days.

PMID- 15719612
TI  - Potential relationship between peripheral blood mitochondrial DNA content and
      insulin resistance and secretion in offspring of type 2 diabetic patients.
AB  - Both qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been
      implicated in the pathogenesis of diabetes mellitus. In this study, we
      investigate whether peripheral blood mtDNA (pb-mtDNA) is decreased and if there
      is any relation between its content and the parameters of both insulin resistance
      and secretion in offspring of diabetic subjects. The pb-mtDNA content was
      measured by real time polymerase chain reaction with mitochondrial- specific
      fluorescent probe, normalized by a nuclear DNA, 28S rRNA gene, in 42 offspring of
      type 2 diabetic patients and 12 age-, sex- and body mass index (BMI)-matched
      normal subjects. The correlations between pb-mtDNA content and the parameters of
      insulin resistance and secretion were studied. Our results indicated that the
      level of pb-mtDNA was lower in offspring of diabetic subjects than in control
      subjects (1230 +/- 0.05 vs. 1513 +/- 0.02 in the offspring and control subjects,
      respectively, P < 0.05). Also, pb-mtDNA content was significantly correlated with
      logarithmically transformed insulin sensitivity index (r = 0.5, P < 0.05),
      fasting C-peptide (r = -0.8, P < 0.05), acute insulin response (r = -0.8, P <
      0.05) and late insulin response (r = -0.7, P < 0.05) in offspring of diabetic
      subjects. In conclusion, quantitative mtDNA status might be a hereditary factor
      associated with type 2 diabetes and is correlated negatively with indexes of
      insulin resistance and insulin secretion in offspring of diabetic patients. So,
      pb-mtDNA content could serve as an indicator of insulin sensitivity and insulin
      secretion in those subjects.

PMID- 15719613
TI  - Trials for preparation of inactivated sheep pox vaccine using binary
      ethyleneimine.
AB  - Binary ethyleneimine (BEI) was used to inactivate the local Egyptian strain of
      sheep pox virus. The inactivation process was applied using final concentrations
      of BEI at 0.5, 1, 2 and 3% for different incubation periods at 37 degrees C. The
      virus was completely inactivated after 7 hours incubation with by 2% BEI final
      concentration; the inactivated virus was adsorbed on aluminium hydroxide gel when
      incubated for 6 hours in a concentration 1:1. The antibody levels were estimated
      by virus neutralization test and ELISA. Specific antibodies appeared from the 1st
      week post vaccination and remained until the 4th week post challenge. The
      prepared vaccine was evaluated for safety, sterility and potency. The vaccine
      proved to be safe, sterile and inducing protection for the vaccinated lambs when
      challenged by the virulent sheep pox virus up to 6 months post vaccination.

PMID- 15719614
TI  - Molecular detection of Babesia equi in infected and carrier horses by polymerase
      chain reaction.
AB  - Twenty-three blood samples were used in this study; five were from five naturally
      infected horses with Babesia equi (B. equi), while eighteen were from
      asymptomatic horses with equine babesiasis from different localities in Egypt.
      All samples were subjected to microscopic examination, indirect fluorescent
      antibody test (IFA) and polymerase chain reaction (PCR). The carrier animals were
      microscopically detected in 7 out of 18 samples (38.8%) and in 9 of 18 by using
      IFA (50%), whereas PCR revealed that 14 samples were positive (78%). Two
      synthetic oligonucleotide primers, based on the B. equi merozoite antigen gene
      (EMA-1) were used. A 819 bps DNA fragment is specifically amplified from the gene
      encoding EMA-1 of B. equi. Our results demonstrate that PCR is a valuable
      technique for routine detection of B. equi in chronically infected horses, even
      at low parasitaemia levels.

PMID- 15719615
TI  - Lymphoproliferative responses of splenocytes before and after challenge with
      Schistosoma haematobium in C57BL/6 mice vaccinated with human anti-Idiotypes.
AB  - Anti-idiotypic vaccines (anti-Id or antibody 2; Ab2) in experimental
      schistosomiasis engender varying degrees of resistance to challenge infection. To
      further characterize the mechanisms involved in the induction of protective
      immunity associated with such a vaccine model, spleen cells of mice vaccinated
      with human Ab2 (HAb2) were investigated for their lymphoproliferative responses
      before and after challenge infection with normal S. haematobium cercariae. HAb2
      was purified from sera of chronically infected patients using protective rabbit
      antibodies (RAb1) isolated from sera of rabbits multiply immunized with UV
      irradiated cercariae by affinity chromatography over soluble worm antigenic
      preparation (SWAP). Vaccination of C57BL/6 (C57) mice with HAb2 resulted in
      approximately 31% and approximately 36% protection in two experiments of
      resistance to infection. Splenocytes were collected prior to challenge at week 6
      post initial immunization and after challenge at days 6, 10, 28 and 90. Prior to
      challenge, in vitro splenic responses of HAb2-vaccinated animals (HAb2-group) to
      phytohaemagglutinin (PHA) declined while both SWAP and HAb2-driven responses
      increased, all compared to naive control. After challenge, PHA responses
      increased in the two test groups on day 6 then significantly decreased to lower
      levels. On the other hand, SWAP- and HAb2-driven responses of HAb2 group
      increased by day 6 then declined while the same responses in infected control
      mice increased on days 10 through 28 and decreased by day 90. Generally,
      proliferation obtained following in vitro stimulation with HAb2 was greater than
      that with SWAP in the HAb2-group after challenge. These results suggested that
      human anti-Id antibodies could mimic at the T cell level the properties of a
      protective antigenic epitopes of the irradiated-cercariae vaccine.

PMID- 15719616
TI  - Assessment of anti-neutrophil cytoplasmic antibodies and selected serum pro
      inflammatory cytokines in systemic lupus erythematosus: prevalence and clinical
      significance.
AB  - This study was designed to elucidate the prevalence and clinical implications of
      various cytokines such as TNF-alpha, IL-6 and IL-2 in presence or absence of anti
      neutrophil cytoplasmic auto- antibodies (ANCAs) in children with SLE. The present
      study was conducted on 29 children with SLE and 20 healthy children of matched
      age and sex as controls. Patients were selected from the Rheumatology Clinic,
      Cairo University Pediatric Hospital. Serum levels of ANCAs, ANA, anti-ds-DNA were
      assayed by an indirect immuno-fluorescence technique (IIF). Serum levels of
      cytokines (TNF-alpha, IL-6 and IL-2) were assayed by ELISA technique. The anti
      neutrophil cytoplasmic auto- antibodies were present in 55% of children with SLE.
      Furthermore, serum levels of TNF-alpha, IL-6 were increased and IL-2 level was
      decreased in SLE children positive for ANCAs. In addition, SLE complications were
      increased in those children. These results demonstrate that ANCAs may be
      detectable in SLE sera and their presence could be associated with particular
      clinical manifestations.

PMID- 15719617
TI  - IL-10 and IL-12p40 in Egyptian patients with HCV-related chronic liver disease.
AB  - Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide
      with a prevalence of approximately 14% in Egypt. IL-10 is a cytokine produced by
      Th2 cells. It down-regulates the proinflammatory response and modulates hepatic
      fibrogenesis. IL-12 is produced by antigen presenting cells. It promotes Th1 cell
      response and has many antiviral properties. Data concerning the Th-1/Th-2 balance
      in chronic hepatitis C (CH-C) are rather conflicting. Using ELISA, we assessed
      serum IL-10 and IL-12p40 levels in 66 Egyptian patients with HCV-related liver
      illness (CH-C, cirrhosis, and HCC), and their relationship to disease activity.
      Our results showed that spontaneous IL-10 was undetectable in patients with CH-C,
      HCC or controls. Only 5/22 (23%) of patients with cirrhosis showed detectable
      levels of IL-10. IL-12p40 was elevated in the patient groups compared to controls
      (p= 0.01, p= 0.01, p= 0.05 in CH-C, cirrhosis and HCC, respectively). The
      presence of IL-12p40 was associated with HCV level of viremia and serum AST.
      Serum ALT level was significantly associated with the level of IL-12p40. IL-12p40
      was unrelated to liver histology or fibrosis. We concluded that in the Egyptian
      patients an augmentation of IL-12p40 and a suppression of IL-10 are both found.
      Whether this pattern is related to HCV genotype 4, or to the presence of
      schistosomiasis would need to be further investigated.

PMID- 15719618
TI  - TT virus infection among Egyptian patients with hepatocellular carcinoma.
AB  - Hepatitis B and C viruses (HBV and HCV) have been associated with hepatocellular
      carcinoma (HCC). Recently, a novel DNA virus was isolated from a patient with
      posttransfusion hepatitis of unknown etiology and designated TT virus (TTV). To
      examine whether this virus is associated with HCC, we investigated sera from 82
      Egyptian patients with histopathologically-diagnosed HCC. All subjects underwent
      serological investigations for detection of hepatitis B surface antigen (HbsAg),
      hepatitis B core antibody (HbcAb) and anti-HCV. Detection of TTV-DNA was
      performed by semi-nested polymerase chain reaction (PCR) using TTV-specific
      primers. TTV-DNA was detected in 28% of the patients. Age, gender, risk factors
      and biochemical liver functions did not significantly differ between TTV-DNA
      positive and negative patients. TTV was detected in 27.1% of patients with HCV
      HCC, 25% of HBV-HCC, 66.7% of dual HCV and HBV infection and 40% of those with
      non-B, non-C-HCC (NBNC-HCC). It is concluded that, in this the cohort of Egyptian
      patients with HCC, TTV infection is common and is not associated with HCV, HBV,
      NBNC-HCC, history of schistosomiasis or blood transfusion.

PMID- 15719619
TI  - Relationship between HLA-DRB1*0101, DRB1*0301 alleles and interleukin-12 in
      haemophilic patients and hepatitis C virus positive hepatocellular carcinoma
      patients.
AB  - The immune system can effectively eliminate hepatitis C virus (HCV) in 15 % of
      acute hepatitis cases. It is assumed that certain HLA-DR alleles present HCV
      epitopes more effectively to CD4 helper T cells than do others resulting in
      vigorous proliferative response to these epitopes and probably HCV recovery. So,
      we aimed at investigating the frequency of HLA-DRB1*0101 and DRB1*0301 alleles in
      child and adult haemophilics and in HCV positive hepatocellular carcinoma (HCC)
      patients in a trial to predict patients who require early therapeutic
      intervention. We also evaluated interleukin (IL)-12 levels in these patients
      since IL-12 induces interferon (IFN)-gamma production. This study was conducted
      on 50 antiHIV negative male patients subdivided into: 25 HCV negative
      haemophilics (group I), 10 HCV positive haemophilics (group II) and 15 HCV
      positive HCC (group III). Fifteen healthy persons of matched age and free of HCV
      and HIV infections were chosen as controls (group IV). All patients and controls
      were subjected to thorough history taking and clinical examination, routine and
      diagnostic investigations, viral markers, DRB1*0101 and DRB1*0301 amplification
      by polymerase chain reaction and plasma IL-12 quantitation by enzyme linked
      immunosorbent assay (ELISA). The frequencies of DRB1*0101 and DRB1*0301 were 20%
      and 30% respectively in HCV positive haemophilics and 13.3% and 40%, respectively
      in HCC. IL-12 levels were significantly lower in HCC cases than in HCV positive
      haemophilics. Among the haemophilics, IL-12 levels were non-significantly higher
      in children than in adults and were associated with the given number of blood
      product bags. DRB1*0101 and DRB1*0301 may have a role in HCV clearance and
      persistence in Egyptian patients with haemophilia and HCC. Low IL-12 levels
      encountered in HCV positive haemophilics suggest its relation to
      immunopathogenesis and outcome of HCV infection.

PMID- 15719620
TI  - Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of
      metalloproteinase-1 as non-invasive markers of hepatic fibrosis in patients with
      HCV related chronic liver disease.
AB  - As chronic liver disease progresses, an imbalance occurs between synthesis and
      breakdown of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are
      involved in degrading ECM while tissue inhibitors of metalloproteinases (TIMPs)
      prevent their fibrolytic action. In the present study, serum levels of matrix
      metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      were investigated as non-invasive parameters for the diagnosis of hepatic
      fibrosis in patients with HCV related chronic liver disease. Their diagnostic
      potential was evaluated in comparison to hepatic histology and standard liver
      function tests. A sandwich enzyme immunoassay technique was used to study
      circulating values of MMP-2 and TIMP-1 in forty-one patients with HCV antibodies
      in their sera (27 patients with biopsy ascertained chronic hepatitis C and 14
      patients with histologically proven liver cirrhosis. Hepatic histology was
      evaluated using the hepatitis-activity-index according to Ishak et al. (1995),
      quantifying separately inflammatory activity and fibrosis. Ten healthy
      individuals were also included in the study as controls. Serum levels of MMP-2
      were similar in controls and in chronic hepatitis C patients with (n = 15) and
      without (n = 12) fibrosis, but increased significantly in cirrhosis. TIMP-1 serum
      values showed a steady increase from normal controls to chronic hepatitis C
      without fibrosis, hepatitis C with fibrosis, and cirrhosis. The diagnostic
      potential of MMP-2 to detect fibrosis was low with a sensitivity of 7% and a
      diagnostic efficiency of 56%. The diagnostic potential of circulating MMP-2 to
      detect cirrhosis was higher with a sensitivity of 83% and a specificity of 96%
      resulting in a diagnostic efficiency of 92%. Serum TIMP-1 values detected
      fibrosis with a sensitivity of 67% and a specificity of 69% resulting in an
      efficiency rate of 70%. TIMP-1 values detected cirrhosis with 100% sensitivity
      but only 75% specificity. The diagnostic potential of circulating TIMP-1 was
      higher than that of serum ALT, AST or albumin values. In conclusion, serum values
      of MMP-2 and TIMP-1 are able to detect cirrhosis with a high sensitivity.
      Moreover, TIMP-1 values can detect fibrosis with comparable efficiency. Regular
      determinations of both TIMP-1 and MMP-2 in patients with chronic hepatitis C may
      be used as indicators of increasing fibrosis and the development of cirrhosis.

PMID- 15719621
TI  - Study of antioxidant enzymes level and phagocytic activity in chronic liver
      disease patients.
AB  - Patients with chronic cholestasis, particularly those with associated cirrhosis,
      are susceptible to infectious complications. A predictable consequence of
      cholestasis is malabsorption of fat-soluble vitamins and free radical scavengers.
      On the other hand, it has been postulated that cholestasis affects
      polymorphonuclear leukocytes function by impeding chemotaxis, phagocytosis and
      superoxide anion release in experimental animals. This work is aimed to evaluate
      the antioxidant status and phagocytic activity of neutrophils in chronic liver
      disease patients. 15 primary biliary cirrhosis (PBC) patients, 15 primary
      sclerosing cholangitis (PSC) patients, 15 chronic viral hepatitis C (HCV)
      patients, and 15 healthy individuals (control group) were included in this study.
      Levels of catalase (Cat), superoxide dismutase (SOD), reduced glutathione (GSH),
      glutathione peroxidase (GPx) and malondialdehyde (MDA) were assessed in both
      serum and neutrophils homogenates. Neutrophils function was estimated by
      nitroblue tetrazolium (NBT) reduction assay. A marked decrease in the antioxidant
      status was observed in serum and neutrophils' homogenate of patients with chronic
      liver diseases compared to healthy subjects. Significant elevation of lipid
      peroxides was found in all groups of liver disease patients. The majority of
      patients had reduced value in NBT reduction assay, which suggested a lack of
      response to infection by neutrophils. In conclusion, deficient antioxidant
      defense mechanisms may lead to excess oxygen free radicals formation that promote
      the pathological process in the liver. The use of free radicals scavengers by
      chronic liver patients may potentiate the antioxidant defense system against
      oxidative stress.

PMID- 15719622
TI  - The role of interferon-gamma and vitamin-A in modulating telomerase activity in
      breast cancer patients.
AB  - Telomerase is a ribonucloprotein enzyme that appears to play a role in
      carcinogenesis. To understand the regulatory mechanisms which govern telomerase
      activity, we used telomeric repeat amplification protocol (TRAP) to quantitate
      and compare telomerase activity in cultured peripheral blood mononuclear cells
      (PBMCs) with and without INF-gamma in breast cancer patients. Serum levels of IFN
      gamma and vitamin-A were also measured to look for a possible influence of these
      chemotherapeutic agents on telomerase activity. 23 premenopausal breast carcinoma
      patients (8 with clinical stage 11, 8 stage III and 7 stage IV) and ten age and
      menstrual stage matched healthy controls were studied. Before surgery, telomerase
      activity and IFN-gamma levels were significantly higher (P<0.001, P<0.05
      respectively) in patients than controls and were associated with significant
      lower (P<0.001) serum level of vitamin-A. After surgery, chemotherapy for 3
      cycles and oral vitamin-A, a sharp reduction in telomerase activity and serum IFN
      gamma levels was observed in all groups of patients compared to the controls.
      Cultivation of PBMCs in the presence of IFN-gamma caused up-regulation (about
      25%) of telomerase activity. However, a significant positive correlation (r =
      0.941; P < 0.001) in telomerase activity was observed between cultured PBMCs with
      and without IFN-gamma in all breast cancer patients before treatment. Positive
      correlation was also found between serum levels of IFN-gamma and telomerase
      activity of cultured PBMCs with and without IFN-gamma (P< 0.01). In contrast,
      negative correlations were observed between serum levels of vitamin-A and
      telomerase activity and serum levels of IFN-gamma (P < 0.01). It is concluded
      that IFN-gamma and vitamin-A may modulate telomerase activity in breast cancer
      patients and this should be considered in developing new strategies to control
      cancer cell growth.

PMID- 15719623
TI  - Leptin in acute leukaemias: relationship to interleukin-6 and vascular
      endothelial growth factor.
AB  - Leptin alone and in combination with other cytokines has a stimulatory effect on
      proliferation of leukaemic cells. This effect may be due to prevention of
      apoptosis of progenitor cells or upregulation of specific receptors on leukaemic
      precursors that make them more responsive to stimuli. This work investigates the
      relationship between serum leptin level, serum interleukin-6 (IL-6) and vascular
      endothelial growth factor (VEGF) in acute leukaemic patients. The relationship to
      blood cell counts, haemoglobin and response to chemotherapy was also
      investigated. The study included 25 acute leukaemic male patients [15 acute
      myeloid leukaemia (AML) and 10 acute lymphoblastic leukaemia (ALL)] and 15 age
      and sex matched healthy controls. All were subjected to thorough history taking,
      clinical examination, complete blood picture, hepatic and renal function tests
      and determination of serum leptin, IL-6 and VEGF levels. In addition, patients
      were subjected to bone marrow aspiration, cytochemistry and immunophenotyping
      study and serum leptin assay after chemotherapy. Serum leptin level showed
      statistically significant elevation only in AML group (p<0.01). This elevation
      was unrelated to the presence of extramedullary infiltration or response to
      chemotherapy and correlated only with body mass index (p<0.05). In ALL, the mean
      serum leptin level was insignificantly different from the controls. In both AML
      and ALL, there was no significant difference in serum leptin level before and
      after treatment. Statistically significant elevation of IL-6 and VEGF,
      uncorrelated with serum leptin level was detected in AML patients when compared
      with the controls. No correlation was found between serum leptin level and any of
      the studied haematological parameters. It is concluded that the release of
      leptin, IL-6 and VEGF may be regulated by different mechanisms leading to
      diversity in clinical features of the disease.

PMID- 15719624
TI  - Eosinophil cationic protein as a diagnostic marker for asthmatic children treated
      by immunotherapy.
AB  - We estimated the eosinophil cationic protein (ECP) levels in serum and sputum of
      20 children with bronchial asthma to find whether it correlates with disease
      activity and examine the effect of immunotherapy. Ten-age- and sex- matched
      healthy children were also included. Children were subjected to full history,
      clinical examination and investigation including skin prick test, chest x-ray,
      complete blood count, and estimation of eosinophil cationic protein. In addition,
      examination of sputum to determine the eosinophil count and eosinophil cationic
      protein level was carried out. Patients were classified into 2 groups (10
      patients each) according to the line of treatment used (5 mild and 5 moderate in
      severity). Group I received pharmacotherapy only and was followed for one year,
      while group II, received pharmacotherapy plus immunotherapy for one year. A
      significant increase in eosinophil count and ECP of blood and sputum was found in
      asthmatic patients as compared to controls. The ECP levels were significantly
      higher in moderate cases when compared with mild cases. On comparing levels of
      both eosinophil count and ECP in peripheral blood and sputum, before and one year
      after treatment, there was a significant reduction after therapy among the two
      groups of patients. The reduction was significant in group II. On the other hand
      there was a significant decrease in both symptoms and medication scores after one
      year of therapy. In conclusion, ECP may be a marker of eosinophilic activity and
      degranulation that correlates with the severity of bronchial asthma.
      Immunotherapy may be a good adjuvant therapy for atopic bronchial asthma of
      childhood.

PMID- 15719625
TI  - Production and evaluation of a monoclonal antibody to Clostridium perfringens
      type D epsilon toxin.
AB  - A monoclonal antibody (mAb) against C. perfringens type D epsilon toxin was
      produced in hybridoma tissue culture supernatant and in BALB/C mice ascitic
      fluid. The mAb reacted with single band of the purified epsilon toxin and
      efficiently neutralized the lethal effect of epsilon toxin in mice. A competitive
      ELISA (C-ELISA) was developed using this mAb and used to evaluate C. perfringens
      type D vaccines. Individual serum samples from vaccinated rabbits were tested
      using C-ELISA and mouse neutralization test (MNT). The mAb based C-ELISA
      correlated with the conventional MNT for estimation of antitoxin level.

PMID- 15719626
TI  - Soluble P-selectin is a marker of plaque destabilization in unstable angina.
AB  - Unstable coronary syndromes usually involve platelet activation and thrombus
      formation at the site of atherosclerotic plaque. P-selectin in platelets and
      endothelial cells mediates adhesive interaction with leucocytes to form thrombi.
      The aim of this study was to asses the level of soluble P-selectin (CD62P) as a
      non invasive marker of coronary plaque destabilization in unstable angina (U.A.).
      Serum samples were collected from 23 male patients with UA, 20 male patients with
      stable angina (SA) and 13 healthy controls. Soluble P-selectin (sP-selectin)
      level was measured by ELISA technique. The mean sP-selectin level was
      significantly higher in patients with UA (87.6+/-30.10 ng/ml) than SA (36.2 +/
      13.8 ng/ml) and control subjects (16.7+/-8.6 ng/ml). In conclusion, s-Pslectin
      level could be used as a marker of plaque destabilization in unstable angina.

PMID- 15719627
TI  - Chlamydia pneumoniae infection in asthmatic patients.
AB  - This study was conducted on 30 asthmatic patients and 10 healthy controls. They
      were subjected to complete history talking, thorough clinical examination, and
      assessment of their ventilatory functions before and after bronchodilator. Two
      specimens were obtained from each patients, bronchoalveolar lavage and serum
      samples. Chlamydia pneumoniae antigens and antibodies (IgG and IgM) were detected
      using microimmunoflourescence technique. Samples giving positive results for C.
      pneumoniae antigen were examined for apoptosis. A significant correlation between
      asthma and C. pnumoniae was found especially in moderate and severe, long
      standing, steroid dependent asthma. In addition there was a significant
      difference between cases and controls regarding specific IgG and IgM. An
      association of C. pneumoniae with forced expiratory volume 1 (FEVI) was found. In
      addition C. pneumoniae was found to induce inhibition of programmed cell death.
      On conclusion, C. pneumoniae infection is associated with severe long standing
      asthma, and may be an important factor in acute exacerbation of asthma.

PMID- 15719628
TI  - [Membrane used for separation of the effective parts and components of
      traditional Chinese medicine].
AB  - Membrane separation, as an efficient and green technology, has found more and
      more research and development reports in the separation and purification of the
      effective parts and components of traditional Chinese medicine. The basic
      principle and mechanism was first described in this paper, and the applicability
      and technological advantage was analyzed accordingly. Then, the separation
      performance of commonly employed membrane materials including polymeric materials
      such as polysulfones, cellulose acetate, polyacrylonitrile as well as inorganic
      materials was compared out and the application examples were presented. Finally,
      the major considerations in choosing the membrane materials were tentatively
      listed, including the physical and chemical stability, the flux and selectivity,
      membrane fouling, and pretreatment of membrane surface.

PMID- 15719629
TI  - [Progress in research on triptolide].
AB  - To further understand triptolide, this paper has introduced the pharmacology,
      pharmacokinetics, toxicity, the clinic application and semi-synthesis of
      triptolide on basis of importance and significant contents of reference which
      have been consulted in the past twenty years. Presently triptolide and
      Tripterygium wilfordii have been a hot spot of modernization of Chinese
      traditional medicine. It is very important to develop a new dosage form of high
      effect and low toxicity by making use of advanced technology according to its
      characteristics.

PMID- 15719630
TI  - [Pharmacognostic studies on Desmodium gyrans].
AB  - OBJECTIVE: To study the characteristic features of Desmodium gyrans in order to
      provide a basis for rational exploitation and utilization of the herb. METHOD:
      Samples of the title plant were collected, the microscopic features of cross
      sections and powders were studied. TLC profiles and UV absorption of the plant
      extract were examined. RESULT: Calcium oxalate crystals were found in cells of
      transverse sections. Nonglandular hairs were observed on leaf surfaces.
      Characteristic peaks in the UV spectrum were identified. CONCLUSION: The distinct
      characteristic features revealed in this studies can serve as evidence for the
      identification of D. gyrans.

PMID- 15719631
TI  - [Studies on quality standard of Peucedanum praeruptorum].
AB  - OBJECTIVE: To establish a quality standard of Peucedanum praeruptorum for Chinese
      Pharmacopoeia (2005). METHOD: The presence of (+/-)-praeruptorin A were
      identified and assayed by TLC and HPLC, respectively. RESULT: Linearity of marker
      was obtained over the range of 0.17696-0.88480 microg (r=0.9999). The average
      recovery rate was 99.72% (RSD=0.40%). CONCLUSION: TLC is specific. The method of
      quantity is accurate, reappearance, simple, rapid, and suitable for the quality
      control of P. praeruptorum.

PMID- 15719632
TI  - [Determination of gallic acid in Melastoma dodecandrum by RP-HPLC].
AB  - OBJECTIVE: To establish a RP-HPLC method for the determination of gallic acid in
      Chinese herb Melastoma dodecandrum, and to evaluate the quality of the herb.
      METHOD: The RP-HPLC analysis was achieved by using a Polaris C18 column and
      tetrahydrofuran-methanol-0.2% phosphoric acid (0.5:0.5:99) as the mobile phase,
      with a flow rate of 1.0 mL x min(-1), and detected by UV at 274 nm. RESULT: The
      content of gallic acid was from 0.020% to 0.081%, in ten groups of M. dodecandrum
      collected from different locations. CONCLUSION: The method is a simple,
      convenient and rapid. It can be used for quality evaluation of M. dodecandrum.

PMID- 15719633
TI  - [HPLC analysis of alfatoxins in medicinal herb extracts by immunoaffinity column
      cleanup and post-column bromination].
AB  - OBJECTIVE: To develop a new and accurate method to quantify aflatoxins in
      medicinal herbs. METHOD: This method consists of sample extraction by using MeOH
      H2O (7:3), followed by clean-up with an immunoaffinity column, and finally HPLC
      determination with fluorescence detection. Aflatoxins B1 and G1 are determined as
      their bromine derivatives, produced in an on-line post-column derivatization
      system. RESULT: The overall average recoveries for different medicinal herbs
      spiked at two levels of standards were from 90.4% to 99.7%. The detection limit
      was 0.06 microg x kg(-1) for aflatoxins G2 and B2, and 0.20 microg x kg(-1) for
      aflatoxins G1 and B1. CONCLUSION: The use of immunoaffinity column provides
      excellent cleanup of interfering substances. The method has been applied
      successfully to analyze 96 natural drugs.

PMID- 15719634
TI  - [Superfine comminution of Glycyrrhiza uralensis roots by vibration mill].
AB  - OBJECTIVE: To discuss the mechanism of superfine comminution of traditional
      Chinese medicine (TCM) at low temperature. METHOD: Glycyrrhiza uralensis roots
      were at room superfinely comminuted temperature and at low temperature by
      cryogenic vibration mill. The superfine powders were observed and analyzed by
      laser particle size analyzer and SEM. RESULT: The powder processed at low
      temperature was of smaller effective diameter and narrower size distribution and
      was also with smoother surface and smaller angle of repose. CONCLUSION: The G.
      uralensis roots could be superfinely comminuted with high efficiency and simple
      procedure by vibration mill at low temperature.

PMID- 15719635
TI  - [Studies on purification of the extract of fructus Gardeniae for injection by
      macroreticular resins].
AB  - OBJECTIVE: To purify the extract of fructus gardeniae for injection by
      macroreticular resins in purification process of traditional Chinese medicine
      (TCM) Injections. METHOD: Using fructus gardeniae as sample, on base of obtaining
      the extract by employing macroreticular resin, quality evaluation and rationality
      of purification methods had been studied by the quantitative analysis of active
      ingredients and the characteristics of micromeritics, safety and stability of the
      extract. RESULT: The experiment showed the extract of fructus gardeniae for
      injection had been produced successfully by macroreticular resin. CONCLUSION:
      Using macroreticular resins is a promising purification way of TCM injections,
      whereas a more consummate method of quality evaluation must be established to
      ensure safety, efficiency and stability of the preparation in the process.

PMID- 15719636
TI  - [Determination of linarin in Yuye Jiedu granule by RP-HPLC].
AB  - OBJECTIVE: To determine the content of linarin in Yuye Jiedu granule. METHOD: A
      HPLC method was developed. The chromatographic conditions are as follows Luna C18
      column and acetonitrile-0.05 mol x L(-1) phosphate buffer-phosphoric acid
      (30:70:0.06) as mobil phase, detection wavelenth at 327 nm. RESULT: The linear
      range of linarin was 0.025-0.50 microg. The average recovery was 98.7% and RSD
      2.7%. CONCLUSION: The method is simple and accurate, with good repeatability, and
      can be used for determination of linarin in Yuye Jiedu granule.

PMID- 15719637
TI  - [Studies on chemical constituents in the mycelia from fermented culture of
      Flammulina velutipes].
AB  - OBJECTIVE: To study the chemical constituents from the mycelia of Flammulina
      velutipes. METHOD: The compounds were isolated with silica gel column
      chromatography and their structures were elucidated on the basis of chemical
      evidences and spectral analysis (IR, EI-MS, 1H-NMR, 13C-NMR). RESULT: Five
      compounds were identified as 5alpha,8alpha-epidioxy-(22E,24R)-ergost-6,22-dien
      3beta-ol (1), ergosta-4,6,8(14),22-tetraen-3-one (2), sterpuric acid (3),
      mannitol (4), ribitol (5). CONCLUSION: The compounds (2)-(5) were isolated for
      the first time from the mycelia of Flammulina velutipes.

PMID- 15719638
TI  - [Studies on the alkaloids from the herb of Corydalis adunca].
AB  - OBJECTIVE: To study the alkaloid constituents of Corydalis adunca. METHOD: The
      constituents were isolated on silica gel column and their structures were
      elucidated by IR, NMR, MS data. RESULT: Eight alkaloid compounds were isolated
      from alcohol extracts of the herb of C. adunca, and identified as
      dihydrosanguinarine (I), tetrahydrocolumbamine (II), 1,2,3,4-tetrahydro-7-methoxy
      1-[(4-methoxy)phenyl]methyl-8-quinolinol (III), protopine (IV) and 6-acetonyl-5,6
      dihydrosanguinarine (V). CONCLUSION: Five compounds were isolated from C. adunca
      for the first time.

PMID- 15719639
TI  - [Studies on chemical constituents in fruit of Rubus chingii].
AB  - OBJECTIVE: To study the chemical constituents of the fruit of Rubus chingii.
      METHOD: The compounds were isolated and purified by recrystallization and
      chromatography with silica gel column and Sephadex LH-20 column. Their structures
      were identified by physicochemical properties and spectral analysis. RESULT:
      Eleven compounds were isolated as oleanic acid (I), ursolic acid (II), maslinic
      acid (III), 2alpha-hydroxyursolic acid (IV), arjunic acid (V), hexacosyl p
      coumarate (VI), tiliroside (VII), stearic acid (VIII), lacceroic acid (IX), beta
      sitosterol (X), daucosterol (XI). CONCLUSION: Compounds I, II, III, IV, V, VI,
      VIII, IX, XI were isolated from R. chingii for the first time.

PMID- 15719640
TI  - [Effect of Shenluotong on secretion of ECM and expression of TGF-beta1 in rats
      mesangial cells of rats].
AB  - OBJECTIVE: To investigate the effect of Shenluotong on the expression of
      transforming growth factor-beta1 (TGF-beta1) and extracellular matrix (ECM) in
      Ang II-induced MCs. METHOD: Fibronectin (FN) and collagen type IV (Col IV) of
      extracellular matrix were detected by enzyme-linked immunosorbent assay; the
      expression of TGF-beta1 mRNA were measured by semi-quantitative reverse
      transcription-polymerase chain reaction. RESULT: A positive correlation between
      TGF-beta1 and ECM were found in the present study. FN, Col IV and TGF-beta1 mRNA
      were inhibited by Shenluotong significantly. CONCLUSION: Shenluotong can decrease
      the accumulation of ECM and inhibit the expression of TGF-beta1, suggesting
      further that shenluotong can be used to prevent and treat various glomerular
      diseases and delay glomerular sclerosis.

PMID- 15719641
TI  - [The protective effects of Fufang Biejiafang on bleomycin-induced pulmonary
      fibrosis in rats].
AB  - OBJECTIVE: To explore the possible effects and mechanism of Fufang Biejiafang on
      a single intratracheal instillation (IT) of bleomycin-induced lung fibrosis
      model. METHOD: SD rats were treated with a single IT dose of bleomycin or control
      saline. Chinese medicine group were poured into the stomach after the first day
      of operation with high dosage, middle dosage and low dosage. On days 7, 14 and 28
      following IT bleomycin or saline, 4 mL blood were taken from the abdominal aorta
      for arterial blood gas analysis. The left lung was fixed for routine light
      microscopic examination. Bronchoalveolar lavage fluid (BALF) from the right lung
      was tested the activity of pulmonary surfactant (PS) by the Whihelmy Film
      Balance, then the right lung was frozen immediately in liquid nitrogen for
      determination of hydroxyproline concentration. RESULT: Model rats had obviously
      changes of body weight and hypoxemia and dysfunction of PS on days 7 and improved
      on days 14. Compared with three dose groups, the middle dose group some degreely
      improved and PS function. It ameliorate fibrosis because of inhibition of
      inflammation. CONCLUSION: (1) PS dysfunction resulted in hypoxemia after
      bleomycin injured alveolar type II (AT II). Fufang biejiafang-middle dose-group
      ameliorate hypoxemia by remission AT-II injury. (2) Fufang biejiafang may inhibit
      exudation inflammation and ameliorate fibrosis.

PMID- 15719642
TI  - [Alteration of activities of telomerase in tanshinone IIA inducing apoptosis of
      the leukemia cells].
AB  - OBJECTIVE: To investigate the effect of tanshinone IIA on HL-60 and K562 cells
      apoptosis, and to assay the inhibition of the telomerase activities in the
      leukemia cell apoptosis induced by Tanshinone. METHOD: Using the techniques of
      cell culture in vitro, flow cytometry and PCR-TRAP observed the telomerase
      activities and apoptosis of HL-60 and K562 cells which treated by Tan IIA.
      RESULT: 0.5 microg x mL(-1) Tan IIA could obviously inhibit HL-60 and K562 cell
      lines growth (P < 0.05), down-regulate c-myc, bcl-2 gene and up-regulate c-fos
      and p53 gene expression as well as induce leukemia cell apoptosis, the apoptotic
      rates of HL-60 and K562 cells were 11.8% and 21.8% respectively. The telomerase
      activities significant decreased, the inhibiting rates in HL60 and K562 cells
      were 30.8% and 50.8% respectively. CONCLUSION: Tan IIA could significantly
      inhibit the proliferation and telomerase activities of HL-60 and K562 cells and
      induce the leukemia cell apoptosis.

PMID- 15719644
TI  - [Experimental study on pharmacodynamical of Oxalis griffithii, a national
      medicine in Guizhou].
AB  - OBJECTIVE: To study the on effects of anti-bacteria, anti-inflammatory and
      pyretolysis of Oxalis griffithii, it is possible safety. METHOD: The mice model
      was established by xylene (auricle smear method) and carrageenin (injection under
      the aponeuroses) respectively, rat febrile model was builded by 2,4-dintrophenol
      injection, and observe the effects of anti-bacteria in vitro that contracted by
      Staph aureus, Escherichia, Shigella, Pseudomonas, Aeruginosa. The mice model of
      experiment study on urgent poison effects (injection under the aponeuroses).
      RESULT: It was found that the mouse ear edema induced by xylene, the increased
      vascular permeability caused by xylene were all significantly suppressed by
      Oxalis griffithii. At the same time, it could depressed the rat fervescence by
      2,4-dinitrophenol. In addition, it has effect on fighting against Escherichia
      coli in cavum abdominis of mice. Oxalis griffithii hasn't canker affect.
      CONCLUSION: These results suggested that Oxalis griffithii had the effects of
      antinflammatory, pyretolysis, and safety.

PMID- 15719643
TI  - [Protective effects of polysacchride of Spirulina platensis and Sargassum
      thunbeergii on vascular of alloxan induced diabetic rats].
AB  - OBJECTIVE: To study the protective effects of polysaccharide of Spirulina
      platensis and Sargassum thunbeergii on vascular of alloxan (ALX) induced diabetic
      rats. METHOD: With the doses of polysaccharide of Spirulina platensis (PSP) and
      Sargassum thunbeergii (PST) compound (1:1) 12.261, 36.783, 110.349 mg x kg(-1) by
      i.g. administration to alloxan induced diabetic rats respectively for 6 weeks.
      Then the blood glucose and the TC, HDL-C, TG, NO, ET in serum were detected. The
      contraction and relaxation response to NE and ACh in aortic rings of the alloxan
      induced diabetic rats has been studied. RESULT: The results showed the compound
      of PSP and PST could decrease the blood glucose and the TC, TG, NO, ET in serum
      and increase HDL-C than in the alloxan induced diabetic rats. The contraction
      responses to NE in aortic rings of the alloxan induced diabetic rats were
      significantly elevated in the normal rats, and the responses to ACh were
      significantly lower. PSP and PST compound could significantly lower the responses
      to NE and significantly elevate the responses to ACh in aortic rings of the
      alloxan induced diabetic rats. CONCLUSION: PSP and PST compound could decrease
      blood glucose and could protect the vascular of alloxan induced diabetic rats.

PMID- 15719645
TI  - [The effects of Baisong tablet on the behaviors and CRHmRNA expression in the
      brain of rats following chronic stress].
AB  - OBJECTIVE: To investigate the effects of Baisong tablet on the behaviors and
      CRHmRNA expression in the chronic stress rats. METHOD: Rats were exposed to
      different ways of chronic stress. Body weight and behaviors were investigated
      during the whole procedure, the CRHmRNA expressions in the hypothalamus and
      prefrontal cortex were semiquantified by the RT-PCR method. RESULT: In
      comparision with the normal group, rats exposed to chronic stress showed
      decreased body weight and a significant reduction of consumption of sucrose
      solution, and the duration of immobility during the forced swimming test was
      increased significantly. The chronic stress rats was in depression of behavior.
      CRHmRNA expression in the brain of the chronic stress rats was upregulated
      significantly, while it was downregulated in the groups of Baisong tablet and the
      group of fluoxetin. CONCLUSION: Baisong tablet has the effect of antidepressant,
      and it may be related to the effect of the downregulated CRHmRNA expression in
      brain.

PMID- 15719646
TI  - [Enhanced absorption of breviscapine photosomes in small intestine of rats].
AB  - OBJECTIVE: To investigate whether the absorption of breviscapine can be enhanced
      by using breviscapine photosomes. METHOD: Testing the uptake and intestinal
      permeability of breviscapine powder and breviscapine photosomes by using
      intestine perfusion technique and reverted gut sac method. RESULT: The uptake and
      permeability coefficient of breviscapine were increased in photosomes. The
      absorption process obeyed the Fick's law in the range of 0-100 microg x mL(-1).
      CONCLUSION: The absorption breviscapine photosomes is enhanced by increasing the
      permeability through a passive mechanism.

PMID- 15719647
TI  - [Analysis of interaction between genetics and environmental life style:
      occupational asthma model].

PMID- 15719648
TI  - [Trend of asthma mortality in Japan].

PMID- 15719649
TI  - [A case of food-dependent exercise-induced anaphylaxis caused by various foods
      which contained flour for thirty years].
AB  - The patient was a 65-year-old man with chief complaints of flare, swelling,
      itching and loss of consciousness. He had a history of diabetes diagnosed at the
      age of 34 years and was receiving medication from a local doctor. He had
      experienced systemic flare, swelling and loss of consciousness 20 minutes after
      drinking beer at a party at the age of 34 years. Since that time, he had
      frequently experienced urticaria and loss of consciousness while taking a walk
      after eating various foods (all of which contained flour). In February 2001, he
      experienced systemic flare, swelling and loss of consciousness when he returned
      home from a walk after eating a meal that included meat dumplings. Laboratory
      tests on admission showed a serum IgE level of 253 IU/ml, and the IgE level for
      flour in a RAST was 2.13 UA/ml (class 2). The results of exercise tolerance tests
      were normal during fasting, after ingestion of food that did not include
      allergens (wheat, shrimps and crab) and after ingestion of half of a thick slice
      of white bread, but systemic wheal and flare reactions appeared during an
      exercise tolerance test after ingestion of one thick slice of white bread. A
      diagnosis of food-dependent exercise-induced anaphylaxis caused by flour was made
      on the basis of the results.

PMID- 15719650
TI  - [Work-relatedness of asthma among outpatients].
AB  - The American Thoracic Society (ATS) issued a statement in 2002 that approximately
      15% of adult asthma was likely to be work related and emphasized the importance
      of prevention for occupational asthma. However, the occupational contribution of
      the burden of asthma has been not understood, because there are very few
      epidemiological studies in the general population in Japan that examined the
      population attributable risk (PAR) of asthma due to occupational exposures.
      Assessing this component of the burden of asthma can better inform preventive
      strategies. Therefore, we examined the PAR of adult asthma due to occupational
      exposures among outpatients by using the National Institute for Occupational
      Safery and Health (NIOSH) criteria. Additionally we examined characteristics of
      cases of work-related asthma. The results indicate that the PAR of asthma due to
      occupational exposures is 22.7%, a value comparable to previous reports in
      Western countries. Therefore, we thought that it suggested that the prevalence of
      work-related asthma in Japan is similar to Western countries. Five patients met
      the criteria for having "probable OA", and their occupations were pest control
      industry, florist, hairdresser and pet groomer. Two patients (40%) changed their
      jobs due to asthma, which suggests that work-related asthma materially affects
      continuation of employment. Four patients (80%) had asthma despite leaving their
      jobs, which suggests that it is crucial to prevent work-related asthma.

PMID- 15719651
TI  - [Evaluation of quality of life (QOL) and efficacy of drug therapy on nasal
      symptoms and QOL disturbances in the patients with Japanese Cedar Pollinosis
      during the season of 2003 in Kyushu and Okinawa districts].
AB  - AIM: The aim of the study is to investigate nasal symptom severity (NSS) and
      disturbance of quality of life (QOLD) of patients with Japanese Cedar Pollinosis
      (JCP) during the JC season of 2003, and to evaluate the efficacy of drug
      treatment on the NSS/QOLD by the data based on disease specific Japan Rhino
      conjunctivitis Quality of Life Questionnaire (JRQLQ). SUBJECTS, METHODS AND
      RESULTS: 3173 patients with JCP from 149 clinics of 8 prefectures in Kyushu and
      Okinawa districts were subjected. Degree of NSS/QOLD was scored as 1 to 4 in
      order (1 for a little and 4 for extremely severe or bothered respectively). (1)
      About 23% of 3173 subjects analyzed complained NSS score > or =3 and about 64%
      score > or =2. About 10% complained QOLD score > or =3 and about 20-30% score >
      or =2. (2) Preventive effect of pre-seasonal medication was analyzed. We
      evaluated the data from 583 patients (177 : received pre-seasonal medication and
      406 : not received) who first answered questionnaire before peak of pollen
      dispersion as the effects on rising-up of symptoms in early stage of pollen
      scattering, and the data from 1223 patients (431 : received pre-seasonal
      medication and 792 : not received) who answered during the whole season as the
      effects on symptoms in whole season. The results of the both analyses indicated
      that the pre-seasonal medication significantly reduced NSS/QOLD in early stage of
      pollen scattering as well as during whole season as a preventive effect. (3)
      Effect of drugs prescribed at the first reply to the questionnaire was analyzed
      in 582 patients who answered the questionnaire twice before and after the peak of
      JC pollen scattering (February 28th), with at least 7 days intervals between 2
      answers. When a proper designate of prescribed drug was not specified, results of
      second answer from 582 patients showed significant reduction of NSS/ QOLD score
      (p<0.001). (4) Single drug which effect was able to be evaluated was anti
      allergic drug (mainly second generation of anti histamine: aH) in 81 cases, or
      anti-leukotriene (aLT) in 25 cases. Although the both drugs were effective, the
      comparison analysis of effectiveness of 2 drugs indicated that effect of aLT on
      reduction of NSS/QOLD score was higher than that of aH. Effect of combination
      drug treatment was able to be evaluated in aH + topical steroids (tS) in 95
      cases, aLT + tS in 12 cases and aH + aLT in 25 cases. Those 3 ways of combination
      were effective, especially the combination with topical steroids with either aH
      or aLT showed significant higher effect on reduction of NSS/QOLD. CONCLUSION:
      JRQLQ is useful questionnaire for general clinic to evaluate the QOL disturbances
      induced by JCP and to follow clinical process relating to QOL changes including
      effect of drug treatment.

PMID- 15719652
TI  - [Are otolaryngologists specialist for pollinosis?].
AB  - It is approved that ENT doctors are specialist for pollinosis. Is it true from
      the point of view of patients' medical care-seeking behavior? 214 patients with
      Japanese cedar pollinosis who had visited medical doctors in 2003 pollen-season
      were randomly sampled from 603 pollinosis patients registered at a disease survey
      company and we mailed self-evaluation questionnaire on patients' medical care
      seeking behavior on the end of pollen season in 2004. Response rate was 65.3%.
      Patients visited clinics in approximately 90% more than hospitals. They selected
      ENT in 43.9% and general physicians in 31.1%. Their selections were based on
      others than their specialty such as easy access and previous experience of visit,
      because pollinosis is not serious disease like cancer. ENT doctors treated the
      patients by combination of two kinds of tablet or topical steroid with tablet,
      while general physicians did with single kind of tablet. The patient
      satisfaction, and its related questions including preference, wish to revisit in
      next year and recommendation to their friend were not different in treatment
      between ENT and general physician. Doctors' attitude, and communication with
      patients were the most important factor for patient satisfaction as well as
      treatment out-come. In conclusion, patients prefer agreeable and convenient
      treatment. If ENT doctors still want to be specialist for pollinosis, they should
      take care patients well and develop their own specific treatment methodology to
      cure this disease.

PMID- 15719653
TI  - [The effect of particle size and amount of inhalation on the pulumonary function
      testsn in asthmatic children].
AB  - The effect of three nebulizers, Nisshou and LC plus, were compared by the
      particle size and amount of inhalation. The improvement of FEV1 at 15 minutes
      after the inhalation was significantly higher in LC plus than Nisshou (MMD:
      7.43microm, 10.76microm). The amount of inhlation were compared between Nisshou
      with/without Y tube and LC plus nebulizer with/without LC valve system. Nisshou
      nebulizer with Y tube and LC plus nebulizer with LC valve systems were
      significantly better than that of LC plus nebulizer without LC valve system.
      Small loss of inhalation gave us better efficacy. The urinary excretion of
      disodium cromoglycate (DSCG) was highest in LC plus with LC valve system, Nisshou
      with Y tube and lowest in Nisshou without Y tube. The elecctric nebulizers
      produced better in MMD of 5microm and a smaller loss of inhalation. These results
      suggested that MMD less than 5microm and small loss from nebulizer are very
      important for inhalation therapy.

PMID- 15719655
TI  - ["DOTS", "DOTS+", and scientific terminology].

PMID- 15719654
TI  - [Mother and two siblings with cockroach asthma].
AB  - We report 2 siblings, an 11 year-old girl and a 10 year-old boy, with cockroach
      asthma who developed the symptoms in May and October, 1999, respectively. Both
      children were considered as psychogenic asthma because of poor familial
      environment and late onset. Their mother also had asthmatic attacks since
      September, 2001. It became clear in the detailed clinical history that their
      rooms had not been cleaned up at all for a long period, and a lot of cockroaches
      had lived in the house. A significantly high titer of cockroach specific IgE
      antibody (CAP-RAST) was detected in all three patients, and cockroach was
      considered as the main allergen of asthma in these patients. Although many cases
      with cockroach allergy including asthma have been reported in United States, it
      has not been recognized well in Japan yet. We would like to emphasize that
      cockroach should be kept in one' s mind as an important allergen of asthma.

PMID- 15719656
TI  - [Main results of researches at the institutions of the Russian Academy of Medical
      Sciences in 2001-2003].

PMID- 15719657
TI  - [The Novosibirsk Research Institute of Tuberculosis, Ministry of Health of the
      Russian Federation is 60 years old].

PMID- 15719658
TI  - [Respiratory fluoroquinolones in the treatment of exacerbations of chronic
      obstructive lung disease].

PMID- 15719659
TI  - [Need for correction of the normative-legal base for implementation of a federal
      program and programs of the subjects of the Russian Federation for Tuberculosis
      Prevention under the conditions of expected stabilization of the epidemic
      situation].
AB  - Evidence is provided for that there is a need for making additions and amendments
      in Federal Law No. 77 "On Prevention of the Prevalence of Tuberculosis in the
      Russian Federation". Amendments are aimed at improving the legal base to increase
      the financing of governmental programs, at organizing the prevention and
      treatment of tuberculosis, at optimizing labor in specialized health care
      services. The authors propose to support the initiative of the Kursk Branch of
      the Russian Society of Phthisiologists for appealing to the State Duma of the
      Russian Federation to submit a legislative initiative in amending the law.

PMID- 15719660
TI  - [Influence of the detection system of patients with tuberculosis on the
      efficiency of their treatment and on epidemiological indices].
AB  - Detection of patients with tuberculosis through timely examinations of groups of
      patients at risk for this disease, which are formed on the basis of testing the
      population and creating its personal register, by using computer technologies,
      makes it possible to improve epidemiological indices and therapeutic
      effectiveness.

PMID- 15719661
TI  - [Problems of drug-resistant tuberculosis in the Republic of Tatarstan].
AB  - The prevalence of drug-resistant tuberculosis in the Republic of Tatarstan was
      studied. Among the bacillary patients with tuberculosis, those who isolated drug
      resistant Mycobacterium tuberculosis were 54.4%; primary drug resistance was
      detected in 31.5% of the patients. In the pattern of drug resistance, multidrug
      resistance was predominant (47.3-75.4%) in all the categories of patients.
      Whether the blood bacteriostatic activity (BBA) could be used to correct a
      chemotherapy regimen in patients with tuberculosis was studied. A direct
      relationship between the level of BBA and a clinical effect was found in new
      cases of patients. When BBA was low, the treatment regimen required correction in
      order to achieve the higher level of BBA. There was no relationship between the
      level of BBA and the results of treatment in patients with chronic tuberculosis.
      The low values of BBA seen in the use of reserve drugs cast any doubt on the
      expedience of their use in chronic tuberculosis.

PMID- 15719662
TI  - [Problems of the epidemiology, diagnosis, and treatment of caseous pneumonia].
AB  - The pace on increases in new cases of caseous pneumonia in 1992-2001 is 50% ahead
      of that in the total number of new cases of pulmonary tuberculosis. Examination
      of the specific features and the course of caseous pneumonia in 128 new cases
      identified the criteria for diagnosing this form of tuberculosis. The leading
      criteria are the X-ray signs of caseous and necrotic lung tissue damage and the
      clinical and laboratory signs of significant endotoxicosis and immunodeficiency.
      The use of extracorporeal immune pharmacotherapy with diucifon in 53 patients and
      the retrosternal administration of isoniazid with hydrocortisone in 43 patients
      showed the efficiency of these methods in the treatment of patients with caseous
      pneumonia.

PMID- 15719664
TI  - [Diagnosis, follow-up, and management in pleural exudate under the conditions of
      a specialized urban consultation service].

PMID- 15719663
TI  - [Effectiveness of an intensive chemotherapy stage in new cases of pulmonary
      tuberculosis and diabetes mellitus].
AB  - Intensive chemotherapy for first detected pulmonary tuberculosis was initiated in
      110 patients with diabetes mellitus (DM). Types 1 and 2 DM was present in 52 and
      58 patients, respectively. In accordance with the WHO recommendations, isoniazid,
      rifampicin, pyrazinamide, and streptomycin or ethambutol were given to the
      patients at the first loading stage. Following 2-3 months, they were treated with
      isoniazid and rifampicin (as well as with pyrazinamide in some cases). A good or
      fair tolerability of the first stage of chemotherapy was noted in 86 (78.2%)
      patients with concurrent pathology (Group 1). The signs of intolerability
      developed in the remaining 24 (21.8%) patients forced them have an individually
      chosen chemotherapy regime instead of the standard one (Group 2). Both groups
      were comparable by age, gender, the pattern of a pulmonary process, the types and
      severity of DM. The effect of treatment was much higher in Group 1 patients.
      According to the data of bacterioscopy and inoculation, bacterial isolation
      ceased in them earlier and achieved more frequently than in Group 2 patients
      (83.7 and 54.5%, respectively; p < 0.05). Better X-ray lung changes were revealed
      after 4-month therapy. Decay cavity closure after 10 months of treatment was
      achieved in 69.3 and 30% of the patients in Groups 1 and 2, respectively (p <
      0.05). Thus, most patients with DM tolerated intensive chemotherapy for pulmonary
      tuberculosis well or satisfactorily. The higher efficiency of this therapy than
      that of individually selected regiment allows the author recommend its wider use
      in patients with this concomitant pathology.

PMID- 15719665
TI  - ["Phthisia-School": a complex action system for a patient with tuberculosis].
AB  - To make the outcomes of treatment in patients with tuberculosis better, a complex
      action system has been developed, by using the data obtained from studies of the
      clinical, psychological, and social characteristics. Four hundred and sixty four
      patients (211 new cases of tuberculosis and 253 with fibrocavernous tuberculosis)
      were examined. The examination was comprehensive and involved a package of
      psychological tests and a special questionnaire survey. Analysis of the results
      of the study made it possible to develop a complex action system for a patient
      with tuberculosis, which was called the "Phthisia-School". It includes the
      provision of positive information, regulated drug therapy, and a corrective
      package aimed at altering the patient's attitude towards to his/her disease,
      intent-to-treat development, enhancing systemic and psychological adaptation.
      There was a statistically significant increase in the efficiency of treatment, a
      tendency towards harmonization of the type of the patient's attitude towards
      his/her disease, a change in this attitude, treatment, personal hygiene rules,
      untraditional treatments, an increase in the discipline of treatment and
      confidence in good prognosis.

PMID- 15719666
TI  - [Impaired lung function in patients with moderate chronic obstructive
      bronchitis].
AB  - VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, RV, Raw, Rin, Rex,
      DLCO-SS, paO2 and paCO2 were determined in 22 patients with moderate chronic
      obstructive bronchitis (FEV1, 79-50% of the normal value). All the patients were
      found to have impaired bronchial patency, 90.9% of the patients had lung volume
      and capacity changes; pulmonary gas exchange dysfunction was present in 72.7%.
      Bronchial patency impairments were manifested by a decrease in FEV1, FEV1/VC%,
      PEF, MEF25, MEF50, MEF75, and an increase in Raw, Rin, Rex. Changes in the lung
      volumes and capacities appeared as higher RV, TGV, TLC, lower VC and FVC.
      Pulmonary gas exchange dysfunction showed up as a reduction in pO2 and DLCO-SS a
      reduction and an increase in paCO2. The magnitude of the functional changes
      observed in most patients was low. Significant and pronounced disorders were seen
      in one third of the patients.

PMID- 15719667
TI  - [Association of pulmonary tuberculosis morbidity with local earth's crustal
      fractures on the territory of a contemporary industrial town].
AB  - The purpose of the present study was to examine the association of the incidence
      and severity of primary pulmonary tuberculosis with the anomalies of physical
      factors (geomagnetic field, gamma-radiation, radon emanation) above the local
      earth's crustal fractures (LECF) on the territory of Surgut. Analyzing the
      findings indicated the significant prevalence of both the rates of total primary
      morbidity of pulmonary tuberculosis and its exudative forms and the predominance
      of bacterial isolating patients among the residents in the area of LECF versus
      the continuum. Antituberculosis therapeutic-and-prophylactic measures should be
      planned, by taking into account the regional features of the state of anomalous
      physical fields.

PMID- 15719668
TI  - [Results of surgical treatment of complicated forms of tuberculous spondylitis].
AB  - The results of surgical treatment of tuberculous spondylitis were studied in 93
      patients, including 45 patients living in poor environmental areas (Group 1) and
      48 residing in good environmental areas (Group 2). The patients underwent
      clinical, laboratory, X-ray tomographic, ultrasound, functional, and electric
      neuromyographic studies. Analysis of the results of the study established that
      despite their short histories of the disease, in Group 1 patients, there was
      affliction of more than 3 vertebrae in 58.1% of the cases, spinal cord
      dysfunction in 42.2%, decreased bone tissue sound conductivity in 8-12% as
      compared with Group 2 patients. A comparative deceleration of graft joining was
      found in 52.4% of the patients. Complete recovery of spinal cord function
      occurred in 87.3% of the cases. A complex conservative and pathogenetic and
      pathogenetic (osteogenon and shilajat-asil) and early surgical treatment of
      tuberculous spondylitis was ascertained to enhance the efficiency of therapy and
      to reduce the length of hospital stay to 1 month.

PMID- 15719669
TI  - [Use of lymphotropic therapy in the multimodality treatment of patients with
      pulmonary tuberculosis and comorbidity].
AB  - Regional lymphotropic therapy involving 10% isoniazid administration was included
      into multimodality treatment in 250 patients with pulmonary tuberculosis and
      comorbidity. The findings have indicated that the lymphotropic therapy during the
      use of rifampicin, streptomycin, ethambutol enhances the efficiency of
      chemotherapy in different forms of pulmonary tuberculosis, including the latter
      concurrent with hepatic lesion or diabetes mellitus. Lymphotropic therapy is
      particularly beneficial to patients with poor drug tolerability. The use of
      lymphotropic isoniazid in the multimodality treatment of pulmonary tuberculosis
      leads to the earlier disappearance of the symptoms of tuberculous intoxication
      (by 1-1.5 months) in 80-92% of the patients, to abacillation in the same periods,
      to the increased frequency of decay cavity closure by an average of 15% as
      compared to the conventional treatment, and, in most cases, to the normalization
      of the biochemical parameters of hepatic function.

PMID- 15719670
TI  - [Applications of polyvinyl alcohol in modern preparations of TCM].
AB  - As a drug additive, polyvinyl alcohol(PVA) has merits of solubility, easy
      forming, strong conglutination, high thermal stability, low toxicity and no
      irritation. In these years, PVA has been applied wider and wider in medicine
      industry. In the study of modem preparations of TCM PVA, as film material of
      membrane and pellicles, is very promising owing to its easy forming and excellent
      toughness. PVA is good polymer matrix for suppositories and gel, because it can
      not only carry drug but also improve the properties of preparations on
      application and technology. It can be said that PVA is an excellent carrier. At
      the present, PVA is mainly applied in vitro preparations of TCM, but its
      applications will be spread with further research. The prospective applications
      of PVA in osmotic pump controlled release preparations, drug carried microspheres
      and swelling controlled release system are foreseen.

PMID- 15719671
TI  - [A new technique of extracting effective components from Chinese herb and natural
      plant--microwave assisted extraction, MAE].
AB  - The extraction and separation of effective components from Chinese herb and
      natural plant is one of the most important processes of natural medicine
      production. Recently, more and more advanced techniques have been used in the
      field of modern Chinese medicines, for example, microwave-assisted extraction
      (MAE). Developed on the base of traditional extracting technology using by
      organic solvents, MAE is of higher extraction rate and efficiency and better
      extract quality, as well as few investment, simple equipment, wide adaptability,
      high selectivity, good fidelity and no pollution. This paper mainly reviews the
      action principle and characteristic of MAE and its application in the extraction
      of natural products such as flavonoids, glycosides, polysaccharides, terpenoids
      and essence. Otherwise, the developing foreground of MAE is also prospected here.

PMID- 15719672
TI  - [Advances in research on chemistry and pharmacology of Sambucus chinensis].
AB  - The progress in research on the active ingredients of Sambucus Chinensis and
      pharmacological activities was reviewed. It is important to study the chemical
      constituents and phamacological activities of Sambucus chinensis.

PMID- 15719673
TI  - [Progress in research on constituents and pharmacological activities of
      sarcotestas of Ginkgo biloba].
AB  - The latest progress in research on constituents and pharmacological activities of
      sarcotestas of Ginkgo biloba has been studied. The main constituents in
      sarcotestas of G. biloba include flavones, ginkgolides, alkylphenols,
      polysaccharides and amino acids, etc. They show the following activities, such as
      bacteriostatic, bactericidal and pesticidal activities, antitumor and mutagenic,
      carcinogenic effects, antianaphylaxis and allergenic activity, effects on
      immunologic function, scavenging free radical, antisenile action, etc. The
      problems at present and the reseach direction for the future on sarcotestas of G.
      biloba have been put forward.

PMID- 15719674
TI  - [Recent research progress of anti-tumor mechnism matrine].
AB  - Matrine, as an active component of Chinese traditional medicine, has a great
      effect on anti-inflammation, anti-arrhythmia and anti-fibrosis of liver cell. But
      the recent evidences indicate that matrine also plays an important role in anti
      tumor, such as inhibiting proliferation, inducing differation and apoptosis,
      reducing invasion and metastasis of tumor cell. In the review we summarized the
      recent research progress of anti-tumor mechanism of matrine.

PMID- 15719675
TI  - [Medicinal plant resources of the Chinese endemic genera of seed plants].
AB  - OBJECTIVE: To survey medicinal plant resources of the Chinese endemic genera of
      seed plants. METHOD: On the basis of herbarium, we studied on more than 800
      specimens of the medicinal plant from Chinese endemic genera of seed plants and
      reviewed literature. RESULT: There are 67 genus, 78 species, 3 varitas in
      medicinal plant from the Chinese endemic genera of seed plants, which belong to
      41 family. Their habitat and medicinal value are provided. CONCLUSION: Medicinal
      plant resources of the Chinese endemic genera of seed plants should be actively
      protected and widely utilized.

PMID- 15719676
TI  - [Studies on plantlet regeneration from the mature leaves of Dioscorea
      zingiberensis].
AB  - OBJECTIVE: To establish a protocol of rapid clonal propagation of Dioscorea
      zingiberensis using mature leaves as explants. METHOD: Out the optimal hormone
      combinations for callus induction, adventitious bud initiation, adventitious bud
      multiplication and rooting were found out by using MS medium with the
      macroelements at half strength as basal medium and studying the effects of BA,
      NAA and IBA on the processes. RESULT AND CONCLUSION: More than 80% of leaf
      explants formed callus when they were cultured on the media containing 1.0 - 5.0
      mg x L(-1) BA and 1.0 - 2.0 mg x L(-1) NAA for 60 days; more than 60% of calli
      initiated adventitious buds within 50 days after they were transferred to the
      media containing 2.0 - 5.0 mg x L(-1) BA and 0.2 - 0.5 mg L(-1) NAA; all the
      adventitious buds rooted well after they were planted on the medium with 2.0 mg x
      L(-1) IBA for 20 days; the regenerated plantlets grew vigorously after they were
      transplanted and the survival rate was up to 80%.

PMID- 15719678
TI  - [IE-HPLC analysis of trigonelline in Fructus Quisqualis].
AB  - OBJECTIVE: To establish a IE-HPLC method for the determination of trigonelline in
      the fruit and seed of Quisqualis indica. METHOD: The method was carried out by
      using Sperisorb SCX column with a mobile phase consisting of 20 mmol x L(-1)
      phorsphate (pH3.2, titrate a 20 mmol x L(-1) monsodium salt with a 20 mmol x L(
      1) solution of phosphoric acid), flow rate of 1.0 mL x min(-1), and the detection
      at 265 nm. RESULT: By using SCX-modified silica column, trigonelline in Fructus
      Quisqualis can be baseline separated and determinated. The retention mechanisms
      proved to be contributed mainly by ion-exchange with the SCX moieties. The
      validity of methods was demonstrated with respect to linearity, precision,
      reproducibility and recovery. It was found that there was no trigonelline
      occurring in the peel of Fructus Quisqualis. CONCLUSION: This assay method can be
      used for the quality control of Fructus Quisqualis.

PMID- 15719677
TI  - [Studies on the technology of directly inducing regenerated plantlet from leaf of
      Chrysanthemum morifolium].
AB  - OBJECTIVE: To set up the fittest medium for directly inducing regenerated
      plantlet from leaf of Chrysanthemum morifolium. METHOD: Leaves of different
      phases obtained from the virus-free plantlets were cut and cultured in some kinds
      of media. RESULT AND CONCLUSION: To Bo morifolium and Chu morifolium, the fittest
      medium for the formation of regenerated plantlet was MS + 6-BA 0.1 mg x L(-1) +
      NAA 0.1 mg x L(-1), and to be incubated on the right side was better than on the
      back right.

PMID- 15719679
TI  - [Pathogenicity of fungi isolated from American ginseng seeds and bioassay of
      fungicides against the pathogenic fungi].
AB  - OBJECTIVE: Detect the pathogenicity of fungi isolated from American ginseng seeds
      and select new fungicides against the pathogenic seed-born fungi. METHOD:
      inoculate the isolates to American ginseng seedlings to detect the pathogenicity,
      and seeded the hyphae disk at the center of agar plate containing chemicals to do
      fungicide bioassay. RESULT: Fusarium sp. isolate 5 and Alternara sp. isolate 13
      had pathogenicity to American ginseng seedling. Sportak had the strongest
      inhibition to the two isolates, Carbendazim had better inhibition and Celest had
      weak inhibition. CONCLUSION: Sportak and Celest could be used as efficacious
      candidate chemicals to treat or coat the American ginseng seeds, and substitute
      Carbendazim, which has been used for many years, to control the diseases
      occurring in seedling stage of American ginseng.

PMID- 15719680
TI  - [Study on chromatogrqphic fingerprint of qingying injection].
AB  - OBJECTIVE: To establish the fingerprint detecting standard of Qingyin injection.
      METHOD: By adopting GC and HPLC, camphor and chlorogenic acid were used as
      reference material. To analyze separately Qingyin injection which contains
      volatile and non-volatile chemials. According to the technical requirements of
      fingerprint on Injection of Chinese traditional medicine, we calculated their bn
      relative retention time and area proportionality of peaks to determine the common
      peaks of fingerprint. RESULT: On the basis of systematic methodalogy, we tested
      and analyzed 13 batches of sample injection so as to establish GC and HPLC
      fingerprint of the injection. CONCLUSION: 15 common peaks on GC and 6 common
      peaks as well as their retention time and area proportionality on HPLC can be
      used as the important parameters of the quality control for Qingyin injection.

PMID- 15719681
TI  - [Chemical constituents from the rhizoma of Arundina graminifolia].
AB  - OBJECTIVE: To isolate and elucidate the chemical constituents from the tuber of
      Arundina graminifolia. METHOD: The compounds were extracted by 95% alcohol and
      isolated by column chromatography on silica gel, SephedaxLH-20 and ODS. The
      structures were determined by UV, IR, NMR and MS spectral analysis. RESULT: Five
      compounds were isolated, and their structures were identified as (2E)-, 2
      propenoic acid, 3-(4-hydroxy-3-methoxyphenyl)-decosyl ester (I), p-hydroxybenzyl
      alcohol (II), triacontanol (III) and p-hydroxybenzylethyl ether (IV), 3-hydroxy-5
      methoxybibenzyl (V), respectively. CONCLUSION: All compounds were isolated from
      the genus of Arundina for the first time.

PMID- 15719682
TI  - [Study on the chemical constituents from Picria fel-tarrae].
AB  - OBJECTIVE: To isolate and identify compounds from Picria fel-tarrae in order to
      utilize it better. METHOD: Constituents from Picria fel-tarrae were isolated by
      several column chromatography and their structures were elucidated on the basis
      of chemical and spectral analysis. RESULT: Six compounds, N-benzoylphenylalanyl-L
      phenylalaninol acetate (1), 1-hydroxy-7-hydroxymethyl-9,10-anthraquinone (2), 9,
      16-dioxo-10,12,14-octadeca-trienoic acid (3), 5,7,4'-trihydroxy-flavone (4), beta
      sitosterol (5), and daucosterol (6) were obtained from the fraction with
      relatively low polarity of EtOH extract of Picria fel-tarrae. CONCLUSION:
      Compounds 1-6 were isolated from picria fel-tarrae Lour for the first time, and
      the 13C-NMR data of compounds 1-3 are provided firstly in the literature.

PMID- 15719683
TI  - [Studies on chemical constituents in bud of Artemisia scoparia (II)].
AB  - OBJECTIVE: To investigate the chemical constituents in flower bud of Artemisia
      scoparia. METHOD: The constituents were isolated and purified by means of various
      chromatographic methods, and spectroscopic methods were used to identify their
      structures. RESULT: Four flavones were isolated and their structures were
      identified as hyperin (V), eupafolin (VI), pedalitin (VII), 5,7,2',4'
      tetrahydroxy-6,5'-dimethoxyflavone (VIII). CONCLUSION: Compounds V, VI, VII, VIII
      were obtained from this plant for the first time.

PMID- 15719684
TI  - [Determination of ligustilide in volatile oil from rhizome of ligusticum
      chuanxiong by RP-HPLC].
AB  - OBJECTIVE: To determine Ligustilide in volatile oil from Ligustrcum chuanxiong
      with RP-HPLC. METHOD: ODS2 column (4.6 mm x 200 mm, 5 microm) was used and
      nitrendipine was used as internal standard. The mobil phase consisted methanol,
      acetontrile and water (33:21:46). The ligustilide was at 275 nm. RESULT: The
      linear range was 2.92-29.2 mg x L(-1) for ligustilide. The average recovery of
      ligustilide was 95.1% and RSD was 2.3%. CONCLUSION: This method is simple and can
      be used to determine ligustilide with satisfactory accuracy and reproducibility.

PMID- 15719685
TI  - [Studies on the chemical constituents of the volatiles of Clerodendron bungei].
AB  - OBJECTIVE: To analyse chemical constituents of the volatiles of Clerodendron
      bungei. METHOD: The volatiles of C. bungei were extracted through steam
      distillation, and then the constituents were separated by GC and identified by
      MS. RESULT AND CONCLUSION: 33 Compounds were identified. The principal chemical
      constituents of the volatiles of C. bungei are ethanol, acetone, 1-penten-3-ol,2
      pentanol, (Z)-2-penten-1-ol, 3-furaldehyde, 3-hexen-1-ol, 4-hexen-1-ol, 1
      hexanol, 1-octen-3-ol, 3-octanol, benzenemethanol, linal-ool oxide, trans
      Linalool oxide, linalool,2,5-dimethylcyclohexanol, phenylethyl alcohol, etc.

PMID- 15719686
TI  - [Studies on anti-hyperglycemic effect and its mechanism of Dendrobium candidum].
AB  - OBJECTIVE: To study the anti-hyperglycemic effect and its mechanism of Dendrobium
      candidum (DC). METHOD: Normal mice, adrenaline-induced hyperglycemic mice,
      streptozotocin-induced diabetic (STZ-DM) rats were used. The mechanisms of the
      anti-hyperglycemic action were studied with radio-immunoassay,
      immunohistochemical HRP-SPA stain, etc. RESULT: DC could not obviously decrease
      the serum glucose concentrations and insulin levels in normal mice. It could
      increase serum insulin levels and decrease serum glucagons concentrations in STZ
      DM rats. The results of immunohistochemical stain demonstrated that the number of
      islet beta cells was increased and that of islet a cells was decreased in STZ-DM
      rats. It could also decrease the serum glucose concentrations and increase liver
      glucogen contents in adrenaline-induced hyperglycemic mice. CONCLUSION: DC has
      obvious anti-hyperglycemic effects in adrenaline-induced hyperglycemic mice and
      STZ-DM rats. Its mechanisms are stimulating the secretion of insulin from beta
      cells and inhibiting the secretion of glucagons from a cells, and it can probably
      decrease the decomposition of liver glucogen and increase the synthesis of liver
      glucogen.

PMID- 15719687
TI  - [Effects of traditional chinese medicine Drynaria fortunei smith on promoting the
      proliferation, differentiation and calcification of mouse osteoblastic MC3T3-E1
      cells].
AB  - OBJECTIVE: To explore the effects of Drynaria fortunei J. Smith (DFS) on
      promoting the proliferation, differentiation and calcification of cells. METHOD:
      Two DFS preparations were extracted with distilled water (DFS aqueous-extract)
      and 95% ethanol (DFS ethanol-extract), respectively. A mouse osteoblast cell line
      MC3T3-E1 was used as a cell model for screening potency of DFS. MTT and Flow
      cytometry were applied to determine proliferation of the cell promoted by DFS
      aqueous-and ethanol-extracts at different dosages. Differentiating effects of the
      two extracts with different concentrations in the cell were evaluated through the
      examinations of alkali phosphate (ALP) activities and osteocalcin levels. Von
      kossa staining method was used to understand the effects of the two extracts
      promoting calcification of the cell. RESULT: 0.01 mg x L(-1) and 1 mg x L(-1) of
      DFS aqueous-extracts showed the proliferative promotion for MC3T3-E1 cell (P <
      0.05). Both the 0.01 mg x L(-1) and 1 mg x L(-1) of the two DFS extracts
      increased the percentages of S-phase cells whereas the percentages of G1-phase
      cells were decreased. 1 and 100 mg x L(-1) of the ethanol-extract remarkably
      increased the synthesis and secretion of osteocalcin of the cell (P < 0.001). 1
      mg x L(-1) of the aqueous-extract and 0.01 mg x L(-1) of the ethanol-extract were
      able to promote the cell calcification (P < 0.05). CONCLUSION: In the DFS aqueous
      and ethanol-extracts, there are some of the components promoting the
      proliferation, differentiation and calcification of osteoblast.

PMID- 15719688
TI  - [Effect of Eucalyptus globulus oil on lipopolysaccharide-induced chronic
      bronchitis and mucin hypersecretion in rats].
AB  - OBJECTIVE: To study the effect of Eucalyptus globulus oil on bronchiolitis and
      mucin hypersecretion in chronic bronchitis induced by lipopolysaccharide in rats.
      METHOD: Rat model was established by intratracheal instillation of
      lipopolysaccharide 0.2 mg. Pathological changes, alteration in bronchoalveolar
      lavage fluid (BALF) and immunohistochemistry characters were examined after 3
      weeks and the effect of E. globulus oil was observed. RESULT: Characters of
      pathological manifestations of chronic bronchitis were found after instillation
      of LPS. Inflammatory cell infiltration and bronchiolitis severity were
      significantly reduced after administration of E. globulus oil. Especially in 300
      mg x kg(-1) treated rats, there were significant decreases of mucin content in
      BALF and MUC5ac expression in trachea and bronchiole epithelium. Optical density
      and mucins area% detected by image analysis system were apparently lower than
      those in model group. CONCLUSION: E. globulus oil has the anti-inflammatory
      effect on chronic bronchitis induced by lipopolysaccharide in rats and the
      inhibitio effect on hypersecretion of airway mucins.

PMID- 15719689
TI  - [Effects of puerarin on plasma membrane GLUT4 content in skeletal muscle from
      insulin-resistant Sprague-Dawley rats under insulin stimulation].
AB  - OBJECTIVE: To explore the effect of puerarin injection on the amount of GLUT4
      protein at the plasma membrane in insulin-resistant rat skeletal muscle. METHOD:
      The rat model of insulin resistance (IR) was made by being fed with high-fat
      diet. The animals were divided into three groups (ten in each group): group I:
      controls; group II: Insulin-resistant rats; group III: Insulin-resistant rats +
      Puerarin treatment. Insulin-resistant rats were injected with 100 mg puerarin
      injection per kg body weight through abdominal cavity once a day for 4 weeks.
      Fasting blood glucose and fasting serum insulin levels were measured before and
      after Puerarin treatment, respectively. Insulin treatment was achieved by
      intraperitoneal injection of insulin (1 unit insulin per kg body weight.) 15
      minute before killing the animals. The right hindlimb skeletal muscle was rapidly
      dissected. Then the expression of GLUT4 protein at the plasma membrane in all the
      animals was assessed with Western blot method. RESULT: The GLUT4 content at the
      plasma membrane in insulin-resistant rats skeletal muscle was significantly lower
      (about 31%) than that of controls (P < 0.01). Puerarin Injection partly corrected
      fasting blood glucose (from 6.17 +/- 0.67 mmol x L(-1) to 5.54 +/- 0.35 mmol x L(
      1)) and fasting serum insulin levels (from 17.09 +/- 2.02 mU x L(-1) to 11.86 +/-
      1.35 mU x L(-1)) and increased the GLUT4 content at the plasma membrane by 1.18
      fold in insulin-resistant rats skeletal muscle. CONCLUSION: Puerarin Injection
      can ameliorate IR, and the mechanism may be involved in increasing cell-surface
      level of GLUT4 through decreasing fasting blood glucose and fasting serum insulin
      levels, improving GLUT4 trafficking and intracellular insulin signaling.

PMID- 15719690
TI  - [Effect of shenwu capsule on the peripheral blood lymphocyte DNA of rat model
      induced by beta-amyloid injection].
AB  - OBJECTIVE: To investigate the effect of the new Traditional Chinese Compound
      Shenwu Capsule on the damage of lymphocyte DNA and lipid peroxidation in
      peripheral blood of rats induced by beta-amyloid injection. METHOD: The animal
      model was made by injection of beta-amyloid25-35 into hippocampus of rats. DNA
      damage of lymphocytes was measured by the single cell gel electrophoresis (SCGE)
      combined with the laser scanning confocal microscopy (LSCM). The content of
      malondialdehyde (MDA) was determined by TBA assay. RESULT: Shenwu Capsule
      decreased the rate of the comet-like cell, comet-like cell lengh (TCL), and tail
      moment (TM) of lymphocytes in peripheral blood of model rats. Shenwu Capsule also
      declined the MDA content in serum of Abeta model rats. CONCLUSION: Shenwu Capsule
      has protective effect on peripheral blood lymphocyte DNA.

PMID- 15719692
TI  - Cancer care. Still no sign of winning tickets in cancer care lottery.
AB  - Postcode prescribing is still a reality in cancer services, says a public
      accounts committee report. Critics claim the large number of small primary care
      trusts is not a good model for commissioning and that money should be 'fast
      tracked' through cancer networks. The report calls for a deadline to be imposed
      for stopping variations in drug prescribing as well as a timetable for
      implementing NICE guidelines.

PMID- 15719691
TI  - [Protective effects of total flavones of metasequosia on cerebral ischemia
      reperfusion injury in rats].
AB  - OBJECTIVE: To observe the protective effects of total flavones of metasequosia
      (TFM) on cerebral ischemia-reperfusion injury in rats. METHOD: The bilateral
      vertebral arteries of rats were occluded under anesthesia, and 4-5 h later the
      carotid arteries of rats in the conscious condition were occluded for 30 min
      followed by reperfusion for 90 min. The effects of TFM on the contents of water,
      Na+, Ca2+ in cortex, malondialdehyde (MDA) content and superoxide dismutase (SOD)
      activity in brain hemispheres, as well as the EEG activities were observed.
      RESULT: After 30 min ischemia and 90 min reperfusion, the contents of water, Na+
      , Ca2+ and MDA were increased, and the SOD activity was reduced with abnormal EEG
      activity and ischemic injury in the brain tissues. TFM 25-100 mg x kg(-1) ip 30
      min before the carotid arteries were occluded, decreased the elevated water, Na+,
      Ca2+ and MDA contents, increased the SOD activity, reduced the ischemic injury of
      brain tissue, and promoted the recovery of EEG activities. CONCLUSION: TFM has a
      protective effect on cerebral ischemia-reperfusion injury in rats.

PMID- 15719693
TI  - No more 'silent stooges'. Interview by Alexis Nolan.
AB  - Non-executive directors are becoming increasingly difficult to recruit, according
      to Sir William Wells, chair of the NHS Appointments Commission. He also warns
      that foundation trust governors face a stiff test in their ability to appoint non
      execs and avoid 'favoured sons or daughters'. In an interview with SHJ, he also
      calls for a greater role for the commission in the development of non-execs.

PMID- 15719694
TI  - Data briefing. Get the measure of delivery.

PMID- 15719695
TI  - Good management. Primary care. How PCT chiefs think ahead.
AB  - A policy think tank for PCT chief executives has been set up by Warwick
      University's Health Service Partnership. It aims to increase PCTs' influence on
      wider policy issues, as well as acting as a networking and research group.

PMID- 15719696
TI  - On clinical management.

PMID- 15719697
TI  - Working Lives. Regional focus: East of England. Playing for keeps.

PMID- 15719698
TI  - What cardiologists do need to know about procalcitonin.
AB  - This review will highlight the potential application of procalcitonin, a novel
      marker of systemic bacterial infection, in two clinical settings relevant to
      cardiologists: infective endocarditis (IE) and lower respiratory tract infections
      (LRTI): The variability in the clinical presentation of infective endocarditis
      (IE) makes the diagnosis a clinical challenge. However, rapid diagnosis and
      initiation of effective treatment are essential to good patient outcome. Serum
      calcitonin precursor levels, including procalcitonin, are elevated in systemic
      bacterial infections and seem to be helpful in the diagnosis of IE. The utility
      of procalcitonin in clinical practice was examined in a prospective cohort of
      patients with the suspicion of IE. Procalcitonin was significantly higher in
      patients with IE (median 6.56 microg/L) as compared with patients with other
      final diagnoses (median 0.44 microg/L, p < 0.001). The area under the ROC curve
      using procalcitonin to predict infective endocarditis was 0.856, as compared to
      0.657 for C-reactive protein. The optimum concentration of procalcitonin for the
      calculation of positive and negative predictive accuracy as obtained from the ROC
      curve was 2.3 microg/L. Using this cut-off, the test characteristics of
      procalcitonin were as follows: sensitivity 81%, specificity 85%, negative
      predictive value 92%, positive predictive value 72%. Although most LRTIs are due
      to viral infections, they are very often treated with antibiotics. This excessive
      use of antibiotics is believed to be the main cause of the spread of antibiotic
      resistant bacteria. A procalcitonin-based therapeutic strategy has shown to
      reduce antibiotic usage in LRTI. Based upon serum procalcitonin levels, the use
      of antibiotics was more or less discouraged (<0.1 or <0.25 microg/L) or
      encouraged (> or =0.5 or > or =0.25 microg/L), respectively. Final diagnoses
      included pneumonia (36%), acute exacerbation of COPD (25%), and acute bronchitis
      (24%). Clinical and laboratory outcome was similar in both groups and favourable
      in 96.7%. In the procalcitonin group, the adjusted relative risk of antibiotic
      exposure was 0.49 (p < 0.001), as compared to the standard group. Thus, using a
      sensitive assay, procalcitonin-guidance substantially and safely reduced
      antibiotic usage in LRTI.

PMID- 15719699
TI  - The use of B-type natriuretic peptide in the diagnosis of acute dyspnoea.
AB  - B-type natriuretic peptide (BNP) and NT-proBNP are currently the most prominent
      members of the natriuretic peptide family. These markers are secreted from both
      the left and the right cardiac ventricle in response to ventricular volume
      expansion and pressure overload. Recent studies have suggested that these
      neurohormones are reliably elevated in the setting of congestive heart failure
      and may be very helpful in its diagnosis. The use of rapid BNP testing in
      addition to clinical judgement increased the accuracy of the clinical evaluation.
      The B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL)
      study showed that the increase in accuracy offered by rapid BNP testing resulted
      in a significant reduction of hospitalisations, use of intensive care, time to
      discharge and initial treatment cost.

PMID- 15719700
TI  - Serum hyaluronic acid levels are elevated in arthritis patients, but normal and
      not associated with clinical data in patients with fibromyalgia syndrome.
AB  - BACKGROUND: Fibromyalgia syndrome (FM) is a disease with widespread chronic pain
      and many nonspecific symptoms. Hyaluronic acid (HA) is a disputed marker for the
      diagnosis of FM. The aim of the study is to clarify the discrepant results
      reported so far. METHODS: Serum concentrations of HA were measured with a
      radiometric assay (Pharmacia & Upjohn, Sweden) in 41 patients with FM (38
      females), 48 with arthritis (35 females) and 31 control subjects (28 females).
      Correlations of HA levels with clinical parameters (duration of disease, age,
      gender, medication) and scores of disease severity (e.g. depression and pain)
      were calculated. If appropriate, partial correlations and analysis of covariance
      adjusted for confounding variables (e.g. age) were used. RESULTS: HA levels were
      confirmed to be age-related in the whole study group (r(s) = 0.54; P < 0.001) and
      each subgroup. Association between HA levels and gender, drug therapy, clinical
      or psychometric data could not be demonstrated in patients suffering from FM.
      Analyzing all study participants, HA levels were correlated with the pain
      disability index (PDI) (r(tau) = 0.27; P < 0.02) and, in arthritis patients only,
      with duration of disease (r(tau) = 0.82; P < 0.001). Moreover, analysis of
      covariance revealed that patients with FM had normal HA values as compared with
      control subjects and only patients with arthritis had significantly higher levels
      than both other groups. CONCLUSIONS: The present study with a quite large cohort
      including patients with arthritis and FM demonstrates that serum levels of HA in
      FM are neither elevated nor associated with any relevant clinical data of this
      disease and, therefore, have no diagnostic or prognostic value in Germans.

PMID- 15719701
TI  - Evolution of the parathyroid hormone (PTH) assay--importance of circulating PTH
      immunoheterogeneity and of its regulation.
AB  - Most of what we know on PTH bioactivity has been associated with the first 34
      amino acids of the PTH structure acting on the type I PTH/PTHrP receptor, leaving
      little place to the carboxyl-terminal structure. This reality has dictated the
      evolution of the PTH assay. The first generation of PTH assays has permitted the
      description of circulating PTH immunoreactivity and of its acute regulation by
      calcium concentration. Most assays reacted with the dominant forms of circulating
      PTH, PTH fragments devoid of bioactivity. This was believed to limit their
      clinical performance, particularly in the diagnosis of hypercalcemic disorders
      and the evaluation of secondary hyperparathyroidism and/or bone diseases
      associated with chronic renal failure. This brought up the development of a 2nd
      generation of PTH assays, the Intact (I) PTH assay. These assays were initially
      demonstrated to react only with hPTH(1-84), the bioactive form of the hormone.
      They greatly improved the differential diagnosis of hypercalcemic disorders,
      facilitated studies of parathyroid function in renal failure patients but were
      still limited in their capacity to dissociate the various bone diseases
      associated with chronic renal failure. Eventually, it was demonstrated that these
      assays, which used 13-34 epitopes, reacted with large C-PTH fragments having a
      partially preserved amino-terminal (N) structure, also called non-(1-84) PTH.
      These fragments accounted for up to 50% of I-PTH immunoreactivity in renal
      failure patients. hPTH(7-84), a surrogate of non-(1-84) PTH fragments, was
      demonstrated to cause hypocalcemia and to antagonize hPTH(1-34) and hPTH(1-84)
      calcemic effect in vivo and to inhibit bone resorption in vitro via a C-PTH
      receptor, different from the type I PTH/PTHrP receptor. This suggested a dual
      control of calcium concentration via N- and C-PTH molecular forms. This also
      explained why the ratio of C-PTH fragments/I-PTH was so well regulated both
      acutely and chronically in various experimental conditions. The fact that I-PTH
      assays detected circulating PTH molecular forms with biological effects opposite
      to those of hPTH(1-84) was believed to explain their limitations, particularly in
      renal failure, and prompted the evolution of a third generation of PTH assays.
      The last is based on a 1-4 epitope to reveal PTH(1-84) and not hPTH(7-84). It
      also permits an indirect evaluation of non-(1-84) PTH fragments by subtracting a
      3rd generation PTH value from a 2nd generation PTH value and the calculation of a
      PTH(1-84)/non-(1-84) PTH ratio. The combination of a third generation PTH value
      with the PTH(1-84)/non-(1-84) PTH ratio value has in some studies improved the
      differential diagnosis of bone diseases associated with renal failure. But more
      studies are required to see whether PTH(1-84)/PTH fragment ratios will improve
      the clinical performance of PTH concentrations used alone.

PMID- 15719702
TI  - The Abbott Architect c8000: analytical performance and productivity
      characteristics of a new analyzer applied to general chemistry testing.
AB  - Applying basic potentiometric and photometric assays, we evaluated the fully
      automated random access chemistry analyzer Architect c8000, a new member of the
      Abbott Architect system family, with respect to both its analytical and
      operational performance and compared it to an established high-throughput
      chemistry platform, the Abbott Aeroset. Our results demonstrate that intra- and
      inter-assay imprecision, inaccuracy, lower limit of detection and linear range of
      the c8000 generally meet actual requirements of laboratory diagnosis; there were
      only rare exceptions, e.g. assays for plasma lipase or urine uric acid which
      apparently need to be improved by additional rinsing of reagent pipettors. Even
      with plasma exhibiting CK activities as high as 40.000 U/l, sample carryover by
      the c8000 could not be detected. Comparison of methods run on the c8000 and the
      Aeroset revealed correlation coefficients of 0.98-1.00; if identical chemistries
      were applied on both analyzers, slopes of regression lines approached unity. With
      typical laboratory workloads including 10-20% STAT samples and up to 10% samples
      with high analyte concentrations demanding dilutional reruns, steady-state
      throughput numbers of 700 to 800 tests per hour were obtained with the c8000. The
      system generally responded to STAT orders within 2 minutes yielding analytical
      STAT order completion times of 5 to 15 minutes depending on the type and number
      of assays requested per sample. Due to its extended test and sample processing
      capabilities and highly comfortable software, the c8000 may meet the varying
      needs of clinical laboratories rather well.

PMID- 15719703
TI  - Clinical significance of hematocrit interference in the tacrolimus II
      microparticle enzyme immunoassay: a tentative approach.
AB  - Recently, the possible interference of hematocrit on the results of the Abbott
      Tacrolimus II microparticle enzyme immunoassay (MEIA) has been described,
      although its significance in clinical practice has not been established as yet.
      The aim of our study was the evaluation of the significance of this analytical
      interference in therapeutic tacrolimus monitoring. In 1121 cases selected at
      random over a 9-month period from kidney (n=379) and liver (n=742) transplant
      patients, an estimation was made of errors caused by the hematocrit in the
      results provided by the Tacrolimus II MEIA. In accordance with the available
      data, it was assumed that an error may be produced beyond the range of hematocrit
      values from 30% to 40%, either positive or negative respectively, of 3% per unit
      of hematocrit. The acceptance criterion for accuracy was no more than 15% of
      deviation (error) with respect to the experimental concentration of tacrolimus.
      In 160 cases (14.3%) the results of the Tacrolimus II MEIA would not be
      acceptable due to hematocrit-dependent errors, both with positive (hematocrit
      <25%) in 108 cases (9.7%) and negative values (hematocrit >45%) in 52 cases
      (4.6%). The obtained results demonstrate the practical interest of the subject,
      although additional studies are required in order to validate our approach to the
      clinical significance of this hematocrit-dependent interference in the Tacrolimus
      MEIA.

PMID- 15719704
TI  - Sealing ability of a glass ampoule.

PMID- 15719705
TI  - Evaluation of alkaline phosphatase activity assay for the Reflotron system after
      substitution of the comparison method.
AB  - The alkaline phosphatase (ALP) assay for the Reflotron system is a dry chemistry
      method applicable for decentralized testing. The ALP diethanolamine method has
      been applied as the comparison method, which is now replaced by the more widely
      distributed aminomethylpropanol method. The new comparison method measures ALP
      activities by approximately 59% lower compared to the former method. The
      analytical performance of the newly calibrated ALP Reflotron method was evaluated
      at three clinical laboratories. The study of the imprecision showed coefficients
      of variation ranging from 1.6-3.0% (intraassay) and 2.7-5.7% (interassay). Blood
      samples from liver disease patients (n=192), adolescents (n=40) and pregnant
      women in the third trimester (n=34) were collected in order to evaluate the
      impact of different ALP isoenzymes. The comparison between ALP Reflotron and the
      new comparison method revealed an excellent agreement in Passing-Bablok
      regression analysis (slope: 1.004; intercept: 0.14 U/l; median difference: 0.5%)
      for samples with prevailing liver ALP. However, in plasma samples with
      predominantly elevated bone or placental isoenzyme the Reflotron method measured
      lower or higher activities, respectively (slope: 0.912, 1.394; intercept: -4.16, 
      17.26 U/l; median difference: -10.58, 26.33%). The ALP Reflotron assay is an
      adequate method for decentralized testing. It shows a good precision and
      agreement with the comparison method, although the systematic differences for
      placental and bone ALP isoenzymes have to be considered.

PMID- 15719706
TI  - The latest from the IVD industry: ever-growing importance of laboratory
      diagnostics in treating cardiovascular disease.
AB  - As cause of death, cardiovascular disease ranks top in mortality statistics. High
      blood pressure and other risk factors are common. Every year over 300,000
      patients are admitted to hospitals in Germany for the treatment of acute
      myocardial infarction. Two million patients suffer from cardiac insufficiency,
      although the unrecorded figure is likely to be far higher. Against this
      background and in the light of the fact that an early, sound diagnosis of these
      conditions often saves life, tests have been used for about 50 years in the
      laboratory to detect substances in the blood which are able to identify the
      cardiovascular risk as well as the acute condition.

PMID- 15719707
TI  - The latest from the ivd industry: prevention, diagnosis and therapy of
      osteoporosis.
AB  - At first glance the human bone appears to be solid, rigid and unchangeable. But
      in point of fact this is not so, for a process of change is continuously going
      on, during which bone mass is resorbed and formed. Up until the age of 30 bone
      mass continues to be formed, although at an increasingly slower pace. A few years
      of equilibrium between bone formation and bone resorption follow. Thereafter,
      from about the age of 40, a continuous slow loss of bone mass sets in. This is
      considered to be a normal process of aging. But if the speed of resorption
      exceeds a certain degree and bone resorption increases, osteoporosis can develop
      after several years. Osteoporosis is therefore an illness in which bone mass has
      been massively resorbed over the past years and/or is being acutely resorbed.
      Given the altered demographic structure--an ever larger number of people living
      to an advanced age--the number of people affected by osteoporosis is increasing.
      Once the bone loss reaches a certain degree, there is a greater susceptibility to
      bone fractures. Particularly affected are the vertebrae, the neck of the femur,
      and the forearm.

PMID- 15719709
TI  - What have we learned about critical thinking in nursing?

PMID- 15719708
TI  - Rationale for testing the cardiovascular risk for patients with COX-2 inhibitors
      on the basis of biomarker NT-proBNP.
AB  - Owing to the selective inhibition of PGI2 synthesis, treatment with COX-2
      inhibitors constitutes a potential risk for the increased occurrence of
      thrombotic cardiovascular incidents and of the first-time occurrence or a
      deterioration in pre-existing heart failure. Elderly patients, particularly those
      with a history of ischemic heart disease, hypertension or heart failure, are at
      risk. One key indication for selective COX-2 inhibitors is the chronic treatment
      of patients suffering from rheumatoid arthritis or osteoarthritis. However, these
      patients have an excess cardiovascular mortality, which relates particularly to
      cardiovascular incidents or heart failure. The use of nonselective antiphlogistic
      drugs and COX-2 inhibitors is associated with a higher potential risk in these
      patient groups. In essence, more than 80 million patients worldwide were treated
      with rofecoxib up to its voluntary withdrawal. The high number of patients who
      are still being treated with COX-2 inhibitors or for whom the use of COX-2
      inhibitors is planned justifies the use of a biochemical marker which, as a
      screening instrument, is initially designed to recognize the patients who are
      "ill" despite the lack of symptoms. In asymptomatic patients with NT-proBNP
      levels below the cut-off, high-risk patients require further work-up. Recognition
      of these risk factors is easily accomplished considering the case history and the
      results of an established cardiovascular risk score (e.g. PROCAM score). These
      risk patients should then also be referred for intensive diagnostic work-up. On
      the other hand, symptomatic patients or those with high NT-proBNP levels should
      primarily be referred for more extensive cardiovascular diagnosis before a
      decision is taken concerning the use of COX-2 inhibitors. As an integral part of
      this extensive work-up the determination of NT-proBNP can help to improve the
      accuracy of diagnosis and prognostic assessment. With the exception of patients
      showing symptoms of an unstable coronary heart disease, imminent cerebral
      ischemia, uncontrolled arterial hypertension or decompensated heart failure, the
      use of a COX-2 inhibitor is possible provided special caution is exercised.
      Termination of treatment is advisable if there is a clinical deterioration of
      specific symptoms or signs in those patients (product information). Follow-up
      with NT-proBNP (monitoring) can be helpful in detecting imminent cardiac
      decompensation at an earlier stage in order to take suitable countermeasures.

PMID- 15719710
TI  - Students' voices: listening to their experiences in practice education.
AB  - The experiences of the students in this pilot study demonstrate how students are
      learning to respond to the call of the patient amid the challenges of
      contemporary health care settings. Perhaps these experiences make teachers
      mindful of how students learn to respond, listen to, and know and connect with
      patients for whom they care. How would clinical courses be different if listening
      to and connecting with patients (as the basis for personalizing care) was given
      the same priority as completing particular interventions or demonstrating
      particular skills? What does it mean to students to encounter situations in which
      patients are not being listened to or in which nurses have not connected with
      patients? Research in nursing education is showing how new, student-centered
      pedagogies arise when teachers shift attention from content, and linking content
      to practice, to equally exploring narrative experiences and how students and
      teachers spend their time together (Diekelmann & Smythe, 2004). The voices of
      students gathered in this pilot study suggest that students are perhaps our
      brightest hope for envisioning what to preserve and what to overcome as we reform
      and create compelling, student-centered practice nursing education.

PMID- 15719711
TI  - Reflective writing and nursing education.
AB  - Reflective writing is a valued tool for teaching nursing students and for
      documentation, support, and generation of nursing knowledge among experienced
      nurses. Expressive or reflective writing is becoming widely accepted in both
      professional and lay publications as a mechanism for coping with critical
      incidents. This article explores reflective writing as a tool for nursing
      education.

PMID- 15719712
TI  - Inquiry in baccalaureate nursing education: fostering evidence-based practice.
AB  - With the increasing emphasis on evidence-based nursing practice, nurse educators
      need to more fully implement teaching strategies that help students gain critical
      thinking skills related to inquiry and understand the importance of evidence
      based nursing practice. Research and scholarship emphases in one baccalaureate
      nursing program, student-identified benefits, and challenges associated with
      incorporating inquiry across the curriculum are described in this article. In
      clinical journal entries, students described the following benefits associated
      with curricular emphasis on inquiry: increased interest in evidence-based nursing
      practice and participating in the generation of research; enhanced critical
      thinking skills through the development of knowledge, experience, and
      competencies; increased motivation to continue professional growth and
      development by participating in lifelong learning; the desire to become better
      consumers of research findings; better understanding of the "real world" of
      clinical research; and increased desire to pursue graduate studies in nursing.
      The challenge to promote student growth toward competence in the application of
      evidence-based principles in clinical practice is ongoing.

PMID- 15719713
TI  - Does service-learning increase cultural competency, critical thinking, and civic
      engagement?
AB  - To prepare for community engagement and partnerships with diverse communities,
      nursing students must understand the principles of service-learning, as well as
      the essential skills needed to work within a democracy. The purposes of these two
      pilot tests were to develop a 15-hour service-learning intervention; refine the
      15-hour service-learning intervention; and explore whether participation in the
      intervention made a difference in the critical thinking, cultural competence, and
      civic engagement of nursing student participants. Although the sample was small
      (n = 14), results of paired t tests found that, after the intervention, critical
      thinking scores measured by the California Critical Thinking Disposition
      Inventory were significantly lower (t = -2.23, p = .04), particularly on the self
      confidence subscale (t = 2.29, p = .039); cultural competence scores measured by
      the Inventory for Assessing the Process of Cultural Competence Among Healthcare
      Professionals were significantly lower (t = 4.83, p = .000); and civic engagement
      scores significantly increased (t = -3.54, p = .004).

PMID- 15719714
TI  - Faculty perceptions of critical thinking in student clinical experiences.
AB  - Critical thinking is an essential skill for nurses who practice in complex health
      care systems. This study explored nursing faculty members' perceptions of
      teaching critical thinking to baccalaureate student nurses in clinical settings.
      Six clinical faculty members were interviewed using an ethnographic approach.
      Findings focus on two domain analyses that describe the nature of critical
      thinking and strategies to effectively teach it. Faculty members conceptualized
      critical thinking as "putting it all together" through information seeking,
      reflecting, assigning meaning, problem solving, predicting, planning, and
      applying information. Faculty members perceived that they teach critical thinking
      through a number of approaches that include asking questions, reviewing written
      products, conducting clinical conferences, and evaluating student journals. The
      findings of this study have implications for faculty who seek a clearer
      definition of critical thinking in nursing and a rich description of strategies
      to teach this skill.

PMID- 15719715
TI  - A longitudinal study of baccalaureate nursing students' critical thinking
      dispositions.
AB  - A longitudinal descriptive design was used to examine nursing students'
      dispositions toward critical thinking as they progressed from the Sophomore II to
      Senior II semester in a baccalaureate nursing program in the midwestern United
      States. The California Critical Thinking Disposition Inventory (CCTDI) was
      distributed during week 10 in the Sophomore II, Junior I, Junior II, Senior I,
      and Senior II semesters. Significantly higher CCTDI scores were achieved in the
      Junior I and Junior II semesters, but no significant differences were found when
      comparing the Sophomore II and Senior II semesters. No relationship was found
      between passing the NCLEX-RN, standardized test scores, and CCTDI scores.

PMID- 15719716
TI  - The relationship of critical thinking to performance on the NCLEX-RN.
AB  - This study investigated the relationship of critical thinking to performance on
      the NCLEX-RN. The sample (N = 218) was composed of baccalaureate nursing students
      from a university-based nursing program in the southwestern United States, and
      participants completed two critical thinking instruments: the California Critical
      Thinking Skills Test (CCTST) and the California Critical Thinking Disposition
      Inventory (CCTDI). Results showed that there was a difference between
      participants who passed and failed the NCLEX-RN on both the entry and exit CCTST.
      Students in the pass group also had higher scores on the exit CCTDI, but scores
      for the fail group were comparable with national norms for nursing students. No
      changes in CCTST or CCTDI total scores occurred between program entry and exit,
      and neither instrument was useful in the prediction of NCLEX-RN performance.
      There were no differences in NCLEX-RN performance between the pass and fail
      groups for age or gender.

PMID- 15719717
TI  - Validation of critical thinking skills in online responses.
AB  - Although nursing accreditation bodies have recognized critical thinking as a
      significant outcome for graduates at the baccalaureate and master's levels, no
      consensus exists on its definition and measurements. In addition, schools of
      nursing that are completely online do not agree on how to evaluate critical
      thinking in online responses. This study explains the development of a 10-item
      tool that uses a Likert scale to evaluate critical thinking skills in students'
      online responses in three master's-level courses in a nursing school in the
      midwestern United States. The developed tool has adequate reliability
      coefficients, as measured by Pearson's r and Cronbach's alpha. The critical
      thinking skills of the tested students were adequate in the areas of analysis and
      synthesis but needed improvement in the evaluation domain.

PMID- 15719718
TI  - Performance-based Development system for nursing students.

PMID- 15719719
TI  - Authenic Assessment for RN students: writing case studies and teaching projects.

PMID- 15719720
TI  - [Prevalence of essential urological diseases among rural population of
      Uzbekistan].
AB  - A retrospective one-stage epidemiological trial was made to investigate
      prevalence of urinary infections (UI), urolithiasis (UL) and benign prostatic
      hyperplasia (BPH) among rural population, to reveal latent or initial stages of
      these diseases and to specify preventive policy. 2330 rural one-year-olds and
      older children (n = 345, 14.8%) were covered by a screening examination for
      bacteriuria, leukocyturia, crystaluria and symptoms of the lower urinary tract
      caused by benign prostatic hyperplasia (BPH). UI, UL, BPH were detected in 7.0%
      (70:1000), 17.9% (179:1000) and 17.3% (173:1000), respectively. UI and UL ran a
      latent course. The former needed an antibacterial preventive therapy, the latter-
      prophylaxis of primary lithogenesis. Alpha-adrenoblockers were indicated for BPH
      patients. All the necessary therapeutic and prophylactic measures can be realized
      outpatiently by general practitioners.

PMID- 15719721
TI  - [New approach to improving efficacy and objective assessment of the
      extracorporeal lithotripsy].
AB  - Clinical trials of the generator EMSE 220F XXP were conducted on the lithotriptor
      Dornie C" in the Research Institute of Urology from September 2203 to January
      2004. Extracorporeal lithotripsy (ECL) was made in 158 patients (66 women and 92
      men, age 11-89 years) with different clinical forms of nephrolithiasis. The
      analysis of nephrolith fragmentation showed high disintegration power of the
      generator in all nephrolithiasis forms (97.4%). Maximal energy intensity in ECL
      of nephrolithis was under 7 units, of ureterolithis--10 units. The number of
      additional sessions averaged 11.4%, mean Edose was 49.2 J. Complications of early
      postoperative period was detected in 4 (2.5%) patients. In two of them (1.3%)
      subcapsular hematomas 180 cm3 in size were detected. The other two patients
      developed exacerbation of pyelonephritis early after operation. It was managed
      conservatively. Thus, EMSE 220F-XXP is a novel, highly effective source of
      generation of shock-wave impulses providing finely divided fragmentation of
      uroliths in 97.4% cases. A mean Edose 49.2 J effectively destructs urinary
      concrements of any location with a minimal risk of postoperative complications.
      Maximal intensity regimes should be used carefully with consideration of a high
      risk of traumatic complications.

PMID- 15719723
TI  - [The role of modern aminoglycosides in urological practice].

PMID- 15719722
TI  - [Pathogenetic criteria of nephroptosis].
AB  - The aim of the study was to specify treatment policy in nephroptosis on the basis
      of characteristics of the onset, development and course of the disease. A total
      of 83 patients with nephroptosis were examined. The rotation angles of the kidney
      were summed using standard excretory urograms in clino- and orthostasis.
      Radionuclide nephroscintigraphy, rheorenography were made in 72 patients.
      Statistical processing employed correlation, cluster, discriminant analysis of
      the program Statistica. The method of estimation of the angles of rotation of the
      movable kidney in three planes was introduced. Grouping of patients by the sum of
      the rotation angles appeared more precise in reflecting disorders of intraorganic
      circulation in the kidney than skeletotopic distribution by the nephroptosis
      degree. Standard excretory urograms allow determination of the sum of the angle
      of rotation of the movable kidney and, finally, adequate conservative or surgical
      treatment method. Surgery can correct disorders of intraorganic blood flow by
      creating physiological position for the kidney raising to the due level and
      eliminating rotation.

PMID- 15719724
TI  - [The rate and location of the positive surgical margin and its role in predicting
      recurrence of prostatic cancer].
AB  - To estimate the rate of positive surgical margin (SM) in radical retropubic
      prostatectomy and its role in emergence of prostatic cancer (PC) recurrence, we
      operated 216 PC patients aged 41 to 73 years. Most of the patients had clinical
      stages T2a,b (41.8%) or T3a (35.6%). Stages T1 and T3b were in 18.7 and 3.9%
      patients, respectively.A positive SM was registered in 68 of 193 patients
      (35.2%). Thirty six (52.9%) patients had a focal (solitary or short) SM, thirty
      two (47.1%) had a long SM. The recurrence occurred in 31 (16.1%) patients who, as
      a rule, had long SM. Recurrence-free one-year survival in 104 patients who had no
      SM reached 82%, in 34 patients with focal SM (group 2) it was 83%. Such three
      year survival in group 1 and 2 was 75 and 73.6%, respectively. Thus, recurrence
      free survival in organ-limited process and short SM differed little within 3
      years. The period between 12 and 24 months of follow-up is most risky in relation
      to detection of recurrence in short SM. The group of patients with long SM had
      maximal number of recurrences.

PMID- 15719725
TI  - [Intraprostatic injection of 96% ethanol in experimental animal model].
AB  - Transurethral intraprostatic injection of ethanol (IIE) is a new low-invasive
      method in the treatment of benign prostatic hyperplasia (BPH). We made dog and
      rat experiments to prove safety and efficacy of IIE. The experiment was made on
      10 rats and 10 dogs injected transurethrally (Prostaject device) with 96% ethyl
      alcohol in 10% volume of estimated volume of the prostate. The injection was
      followed by measurement of blood alcohol, the test for hemolysis. Transurethral
      ultrasound control of prostate size 1, 3 and 6 months after the injection and
      histological examinations 1, 3, 7, 14 days and 1, 3 and 6 months after the
      injection were made. It was found that blood alcohol after the above injection
      was not elevated. Necrosis was documented in all the cases but subsequently the
      necrotic site was replaced with sclerotic tissue. The necrosis involved only the
      prostatic capsule. The size of the prostate diminished by 29%. Thus,
      transurethral injection of ethyl alcohol (10% of prostate size) is safe and
      effective in achievement of prostatic gland ablation. Therefore, clinical trials
      of the method in patients with benign prostatic hyperplasia are justified.

PMID- 15719727
TI  - [Injuries of the urinary bladder: tactics and results of treatment].
AB  - A retrospective analysis of 87 cases of isolated traumas and multitraumas of the
      urinary bladder treated in 1986-2002 covered 69 men and 18 women aged 21-79
      years. Young and middle-aged patients (20-50 year olds) prevailed. Isolated
      traumas of the bladder were diagnosed in 52 patients (4 extra- and 48
      intraperitoneal trauma), 35 patients had multitraumas (7 extra- and 28
      intraperitoneal trauma). Isolated traumas were most frequently caused by beating
      (79.4%), multitraumas--by road accidents (79.2%). Examination included
      catheterization of the bladder, ultrasonic investigation, x-ray contrast studies,
      laparocentesis, laparoscopy. Injury of the bladder combined with fractures of
      skeletal bones, craniocerebral trauma, abdominal injuries. Surgery was made in 86
      cases, bladder drainage was made by cystostomy, transurethral drain was conducted
      in 17 patients. Bladder surgery was combined with abdominal operations in 14
      patients. Three operations were delayed. Out of 87 patients 67 was cured. 20
      (23%) patients died. Lethal outcomes were mostly due to progression of traumatic
      shock.

PMID- 15719726
TI  - [Intravesical ionophoresis of medicines (an experimental study)].
AB  - The depth of drug penetration into the wall of the urinary bladder in
      intravesical ionophoresis (IVIP), IVIP influence on functional condition of the
      lower urinary tracts were studied on 15 female dogs. Functional condition of the
      lower urinary tracts was characterized by pressure in the urinary bladder,
      "volume-pressure" index, bioelectric activity of the urethra. The pressure was
      registered by electromanometry. Bioelectric activity of the urethra was studied
      with electromyography and tetrapolar rheography. The above indices were
      registered synchroneously on a multichannel recorder. Intraoperative
      cystomanometry was made in 7 tyopental narcotized animals. Samples of blood and
      vesicular tissue were taken for immunofluorescent study before and after IVIP.
      Medicines were accumulated best in mucous and submucous layers (0.039 +/- 0.0012
      and 0.0338 +/- 0.0050 mcm/mg tissue, respectively). After IVIP intravesical
      pressure was, on the average, lower in the same filling volumes as before IVIP. A
      mean amplitude of spontaneous fluctuations of pressure in the urinary bladder in
      its filling after IVIP was also lower than the baseline. After IVIP, pressure in
      the urinary bladder in voiding was much lower than before the procedure, maximal
      capacity of the urinary bladder and elasticity of the wall increased.
      Bioelectrical activity of the urethral wall was registered in the same mean
      pressure and capacity as before IVIP. Intensity of micturition after IVIP course
      decreased both at rest and in diuretic load with lasix. Time to micturition was
      increased with an increase in the number of procedures of IVIP. Thus, the
      experimental study showed pathogenetic validity of intravesical ionophoresis of
      medicines in the treatment of chronic recurrent cystitis.

PMID- 15719728
TI  - [Male infertility treatment using KAP-ELM-01 apparatus complex "Andro-Gin"].

PMID- 15719729
TI  - [Fluorescent cystoscopy and transurethral electroresection in diagnosis and
      treatment of patients with invasive cancer of the urinary bladder].
AB  - From 1996 to 2002 we examined and treated 224 patients with invasive cancer of
      the urinary bladder (ICUB). The examination complex included clinical,
      laboratory, radiation tests, endoscopic and morphological investigations of the
      surgical material. The patients received four types of treatment: transurethral
      resection (TUR) of the bladder wall (n = 102) alone; TUR+MVAC chemotherapy (n =
      56); open resection of the urinary bladder only (n = 38); open resection+MVAC
      chemotherapy (n = 28). In diagnosis of papillary lesions sensitivity of
      cystoscopy (CS) was 66.6%, fluorescent CS (FCS)--95.2%. Sensitivity in diagnosis
      of squamous tumors was 33.3 and 91.6%, respectively. The best results were
      achieved in patients with pT2A tumor invasion depth, G1 differentiation of tumor
      cells after TUR with adjuvant polychemotherapy (PCT) recurrences in these
      patients arose by 41.2% less frequently than in patients after TUR only, 5-year
      survival in patients after TUR+PCT was 83.3%. Thus, FCS improves diagnosis of
      urinary bladder tumors (sensitivity of CS was 70.0% vs that of FCS--95.0%). In
      cancer of the urinary bladder the organ can be saved only at stage pT2G1. A
      method of choice is TUR of the bladder wall with adjuvant PCT.

PMID- 15719730
TI  - [Optimization of endosurgical treatment of women with stress urine incontinence].
AB  - Stress urine incontinence was treated in 79 women with Burch laparoscopic
      colposuspension, 75 (94.9%) of them had chronic urinary infection. 42 females of
      group 1 received postoperative extracorporeal hemocorrection, 37 females of group
      2 received conventional postoperative therapy. In group 1 the treatment reduced
      leukocyturia, bacteriuria was detected in 9 (21.4%) patients, recurrent
      incontinence occurred in 2 (5.9%) women. In group 2 leukocyturia enhanced,
      bacteriuria and incontinence recurrence were observed in 23 (62.2%) and 8 (23.5%)
      patients, respectively. The results of the study show that combined use of
      laparoscopic colposuspension by Burch and extracorporeal hemocorrection improves
      the results of the treatment of stress urine incontinence.

PMID- 15719731
TI  - [A case of pigment metabolism disorder in differential diagnosis of urological
      diseases].

PMID- 15719732
TI  - [Primary extraperitoneal scrotoinguinal hernia of the bladder].

PMID- 15719733
TI  - [Peculiarities and difficulties of diagnosis and surgical treatment of urogenital
      echinococcosis].

PMID- 15719734
TI  - [Modern methods of therapy for prostatic cancer of T3N0M0 stage (Part II)].

PMID- 15719735
TI  - [Stages in development of ureterosygmostomy--from Simon-type operation to current
      conceptions of detubulized reservoirs].

PMID- 15719736
TI  - [Duloxetin--a new tool in pharmacotherapy of urinary incontinence in women].
AB  - Urinary incontinence (UI) is represented clinically by stress, urgent, mixed
      forms. Until recently, effective pharmacological treatment of stress UI was
      absent. Now, attempts are made to try duloxetin to raise efficacy of conservative
      treatment and quality of life in patients with stress and mixed UI. A large,
      double blind, placebo-controlled, randomized phase II trial provided data on
      efficacy of duloxetin in the treatment of stress and mixed UI in women. Duloxetin
      led to a decrease in the number of incontinence episodes, a rise in quality of
      life. It was rather effective in severe UI. Phase III trial of duloxetin in a
      dose 80 mg/day reduced the number of incontinence episodes by 50% in most of the
      patients and in some of them cured the patients.

PMID- 15719737
TI  - [Recollection].

PMID- 15719738
TI  - [Insist on the guiding principle of integrative Chinese and Western medicine with
      clear-cut stand].

PMID- 15719739
TI  - [About some problems of integration of Chinese and Western medicine and
      "Westernization of traditional Chinese medicine].

PMID- 15719741
TI  - [Relationship between sCD44v6 expression and TCM differentiation type of gastric
      carcinoma patients and influence of weitai capsule on the expression].
AB  - OBJECTIVE: To explore the relationship of TCM type with serum level of soluble
      CD44v6 (sCD44v6) and different histologic parameters in gastric carcinoma
      patients and to observe the influence of Weitai capsule (WTC) on the sCD44v6
      expression. METHODS: TCM typing and sCD44v6 expression were determined in all the
      enrolled patients (30 in the control and 32 in the trial group) before operation,
      and 3-4 courses of chemotherapy was applied to them from 3-4 weeks after
      operation. To the patients of trial group, oral administration of WTC was given
      additionally with 4 capsules, 3 times a day for consecutive 3 months. RESULTS:
      sCD44v6 was significantly positive correlated with the degree of cancer cell
      differentiation, infiltration and lymph node metastasis; (2) Level of sCD44v6 was
      the highest in patients of blood stasis type, as compared with that in the
      patients of Pi-deficiency type or of damp-heat type, the difference was
      significant; (3) After ending treatment, level of sCD44v6 in the trial group was
      significantly lower than that in the control group. CONCLUSION: (1) Serum level
      of sCD44v6 could be taken as the criterion for evaluating the development and
      prognosis of gastric cancer, as well as the therapeutic target for anti
      metastasis treatment; (2) Serum level of sCD44v6 is related to some extent with
      TCM type of blood stasis and Pi-deficiency; (3) WTC combined with chemotherapy
      could further inhibit the expression of serum sCD44v6 in gastric carcinoma
      patients.

PMID- 15719740
TI  - [Analysis on the prognostic factors in patients with large hepatocarcinoma
      treated by shentao ruangan pill and hydroxycamptothecine].
AB  - OBJECTIVE: To observe the effect of intervention therapy with Shentao Ruangan
      pill (SRP) and hydroxycamptothecine (HCPT) in treating 85 patients with middle
      advanced large hepatocarcinoma, and to analyze the factors that could affect the
      prognosis. METHODS: Eighty-five patients were randomly divided into the treated
      group (n = 52) and the control group (n = 33). The treated group was treated by
      oral taking of SRP combined with local perfusion of HCPT through hepatic artery
      catheterization, while to the control group, the conventional therapy,
      transcatheter arterial chemoembolization (TACE) was conducted for control. The
      clinical efficacy of treatment in the two groups was evaluated by the change of
      tumor size, the factors related with prognosis were analyzed using Cox
      proportional hazards model and the analysis of survival conducted by Kaplan-Meier
      method. RESULTS: (1) The tumor size reducing rate in the treated group was 19.2%
      and the tumor size stabilizing rate was 82.7%, while those in the control group
      was 21.2% and 81.8% respectively, comparison of the criteria between the two
      groups showed insignificant difference (P > 0.05); (2) The median survival time,
      0.5- year, 1- year and 2- year survival rate in the treated group was 326 days,
      80.95%, 41.39% and 12.42% respectively, those in the control group was 262 days,
      64.29%, 25.00% and 8.33% respectively, comparison between the two groups showed
      significant difference (P < 0.05); (3) Among the 3 TCM types in patients, the
      survival time and rates in patients of Gan-excess with Pi-deficiency type was
      similar to those in patients of Gan-heat with blood stasis type showing
      insignificant difference (P > 0.05), but as compared with those in patients of
      Gan-Shen Yin-deficiency type, the difference was significant (P < 0.05) ; (4)
      Beneficial factor to the prognosis were therapeutic method, that used in the
      treated group was superior to that used in the control group. The risk factors to
      the prognosis were TCM type, clinical stage and liver function. Patients of Gan
      excess with Pi-deficiency type had the optimal prognosis, those of Gan-heat with
      blood stasis type the next and of Gan-Shen Yin-deficiency the worst. The later
      the clinical stage and the worse the Child-Pugh grade of liver function was, the
      worse the prognosis would be. CONCLUSION: (1) SRP combined with HCPT intervention
      treatment is superior to the simple TACE treatment in elevating patients'
      survival rate and time; (2) There are some relations between TCM types and
      prognosis; (3) Local Chinese drug therapy combined with systemic therapy could be
      one of the effective measures of non-operational therapy in treating large
      hepatocarcinoma.

PMID- 15719742
TI  - [Relationship between CD8+ T-cell CD28 expression and TCM differentiation type in
      patients with chronic aplastic anemia].
AB  - OBJECTIVE: To explore the relationship between CD8+ T-cell CD28 molecular
      expression in peripheral blood and TCM type in patients with chronic aplastic
      anemia (CAA). METHODS: Using flow cytometry to detect the CD28 expression in 45
      in-patients or out-patients and 24 healthy subjects for control. And the relation
      with TCM type was analyzed from the immunological aspect. RESULTS: (1) The levels
      of CD8, CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all higher in
      the CAA patients than those in the healthy subjects (P < 0.05 or P < 0.01). (2)
      The levels of CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28- were all
      higher in the CAA patients of Shen-Yin deficiency type than those in the CAA
      patients of Shen-Yang deficiency type (P < 0.05 or P < 0.01). CONCLUSION: (1) The
      abnormal high expression of peripheral blood co-stimulatory molecules CD28
      suggested CD28 disorder may play an important role in immuno-pathogenesis of CAA.
      (2) The levels of peripheral CD28, CD8+ CD28+ expression and CD8+ CD28+/CD8+ CD28
      can be taken as an objective indexes for TCM typing of CAA, which was disordered
      more severe in patients of Shen-Yin deficiency type than in those of Shen-Yang
      deficiency type.

PMID- 15719744
TI  - [Relationship between phlegm-stasis syndrome and fibrinolytic status in patients
      with non-alcoholic fatty liver].
AB  - OBJECTIVE: To explore the relationship between phlegm-stasis syndrome (PSS) and
      the fibrinolytic status in patients with non-alcoholic fatty liver (NAFL).
      METHODS: Seventy patients with NAFL were divided into the PSS group and non-PSS
      group according to TCM Syndrome typing, and a control group consisted of 28
      healthy subjects was set up. Levels of plasminogen (PLG), tissue plasminogen
      activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D-dimer were
      determined and compared. RESULTS: The activity of t-PA in NAFL patients was
      significantly lower than that in the control group (P<0.05), and PLG and PAI-1
      were significantly higher than those in the control group (P<0.05). In respect to
      the TCM Syndrome typing, in patients of PSS, t-PA was significantly lower and
      PLG, PAI-1 were significantly higher than those in patients of non-PSS (P<0.05 or
      P<0.01), while D-dimer was insignificantly different between patients of the two
      Syndrome types (P>0.05). CONCLUSION: NAFL patients of PSS type shows significant
      lower of fibrinolytic activity, indicating that there is certain degree of
      microcirculatory disturbance and hyper viscosity state, so the application of
      dissolving phlegm and dispelling stasis principle in treating NAFL is
      significant.

PMID- 15719743
TI  - [Clinical study on treatment of fatty liver by shennong ganzhining].
AB  - OBJECTIVE: To observe the therapeutic effect and safety of Shennong Ganzhining
      (SG) in treating fatty liver. METHODS: One hundred and ninety patients with fatty
      liver were randomly divided into two groups. The 142 patients in the treated
      group received SG and the 48 in the control group received Zhibituo treatment for
      3 months. The comprehensive therapeutic effect after treatment, symptoms, signs,
      liver function, blood lipids and blood viscosity, as well as iconographic
      parameters were observed. RESULTS: The total effective rate in the treated group
      was 80.98%, which was higher than that in the control group (75.00%), showing
      significant difference statistically (P < 0.05). Satisfactory effect was obtained
      in recovery of liver function, improvement of blood lipids, blood viscosity and
      iconographic parameters, no severe adverse reaction occurred. CONCLUSION: SG is
      obviously effective in treating fatty liver with favorable safety.

PMID- 15719745
TI  - [Effect of compound salvia injection on nitrate ester tolerance].
AB  - OBJECTIVE: To investigate the effect and mechanism of Compound Salvia injection
      (CSI) on nitrate ester tolerance. METHODS: Eighty-four patients with coronary
      heart disease (CHD) were randomly divided into three groups, Group A treated with
      isosorbide dinitrate (ISD, 15 mg, 4 times per day) alone, Group B with ISD plus
      CSI and Group C with ISD plus vitamin C. The therapeutic course for all groups
      was 10 days. The tolerance to nitrate ester and blood pressure were monitored.
      Before and after treatment, the color Doppler ultrasonic apparatus was used to
      detect the baseline value of humeral arterial internal diameters (D0), the
      humeral arterial dilatory response under compression [D1, that is, the flow
      mediated vasodilation (FMD)] and the vasodilatory response after sucking of
      nitroglycerin (D2). And the blood levels of endothelin-1 (ET-1), endothelial
      nitric oxide synthase (eNOS) mRNA expression were determined. The endothelial
      dependent vasodilation (EDD) was expressed by (D1 - D0)/D0 x 100%, and the
      endothelial-independent vasodilation (EID) was expressed by (D2 - D0)/D0 x 100%.
      RESULTS: (1) The occurrence rate of nitrate tolerance in Group B and C (28.57%
      and 35.7%) was lower than that in Group A (64.29%), but insignificant difference
      was found between the former two. (2) After treatment, blood pressure increased
      in Group A to the level of pre-treatment, that in Group C also increased but
      still lower than that of pre-treatment, while insignificant increase was observed
      in Group B, comparison between Group B and C showed significant difference (P <
      0.05). (3) After treatment, EID lowered in Group A, EDD increased in Group B and
      C (P < 0.05), EDD and EID in Group B and C were higher than those in Group A (P <
      0.05), and EDD was higher in Group B than in Group C (P < 0.05). (4) After
      treatment, ET-1 mRNA expression lowered in Group B, eNOS mRNA expression
      increased in Group B and C, with significant difference as compared with those
      before treatment and those in Group A (P < 0.05), and eNOS mRNA expression in
      Group C was lower than that in Group B (P < 0.05). CONCLUSION: CSI could
      partially prevent the occurrence of tolerance to nitrate ester, with the effect
      better than vitamin C, the mechanism might be related with its regulation on
      eNOS, ET-1 mRNA expression and protection on vascular endothelial function.

PMID- 15719746
TI  - [Effect of zhitiaokang capsule on serum insulin-like growth factor-2 in patients
      with hyperlipidemia].
AB  - OBJECTIVE: To observe the effect of Zhitiaokang capsule (ZTK) on serum insulin
      like growth factor-2 (IGF-2) in patients with hyperlipidemia (HLP). METHODS:
      Patients with HLP were randomly divided into the treated group (n = 124) and the
      control group (n = 62), they were treated by ZTK and Zhibituo tablet respectively
      for 8 weeks as one therapeutic course. The changes of blood lipids and serum IGF
      2 before and after treatment were observed. RESULTS: ZTK could significantly
      reduce blood lipids and increase serum content of IGF-2. CONCLUSION: ZTK could
      improve the insulin resistant status and inhibit the development of
      hyperlipidemia in patients by means of raising serum content of IGF-2 and
      suppressing vascular endothelial cell apoptosis.

PMID- 15719748
TI  - [Effect of yixin capsule on plasma endothelin and angiotensin II content in
      patients with coronary heart disease of qi-stagnant with blood-stasis type].

PMID- 15719747
TI  - [Primary discussion on the classification of the TCM patterns and measurable
      diagnosis of 760 cases of protracted abstinent syndrome by heroin-addiction].
AB  - OBJECTIVE: To discuss the TCM pattern classification and measurable diagnosis
      criterion of the protracted symptoms of heroin-addiction abstinence (PSHAA).
      METHODS: Through literature review and clinical study, the concept of TCM
      patterns and diagnostic standard were established, and a TCM pattern scale for
      quantitatively analysis of PSHAA was formulated. The scale were used on the
      clinical investigation on the abuser for 5 times on day 15, 30, 60, 90 and 120
      after abstinence. Then the TCM patterns of PSHAA was classified using methods of
      DME and quantitative diagnosis, to create a corresponding scale of diagnostic
      indexes referring maximum likelihood method. RESULTS: (1) The TCM patterns of
      PSHAA commonly seen were Toxin-stasis accumulation (TSA) with Qi-blood
      insufficiency, TSA with Qi-yin deficiency, TSA with Yin-deficiency and Fire
      excess and TSA with Yin-Yang deficiency. (2) The retrospective and prospective
      verification of the scale of diagnostic indexes showed it has high sensitivity
      and speciality, with low rates of misdiagnosis and of missed diagnosis.
      CONCLUSION: It is feasible to develop measurable diagnosis on the TCM patterns of
      PASAA using DME method and measurable diagnostic methods. The scale of diagnostic
      indexes formulated with the maximum likelihood method of quantified diagnosis has
      a certain clinical practicability.

PMID- 15719749
TI  - [Effect and mechanism of rhubarb on fibrinolysis in secondary damaged central
      nerve system of rats with acute hemorrhagic stroke].
AB  - OBJECTIVE: To observe the effect of rhubarb in treating secondary damage of
      central nerve system (CNS) in rats with acute hemorrhagic stroke (AHS) and to
      explore the possible mechanism. METHODS: The rat's AHS model was established by
      autologous blood injection, the effect of rhubarb on the secondary damage of CNS,
      plasminogen (PLG) in brain and tissue type plasminogen activator (t-PA) were
      observed. RESULTS: (1) The nerve function deficit signs reappeared in about 70%
      model rats 4 - 6 days after modeling and reached the peak at day 6 - 8, scored as
      1.63 +/- 0.72 on day 4 and as 2.32 +/- 1.12 on day 7; (2) Rhubarb could
      effectively improve the secondary nerve function damage, with the nerve deficit
      scores kept to 1.24 +/- 0.19 from day 4 on, and no sign of secondary CNS damage
      was shown. The nerve deficit score was 1.22 +/- 0.15 on day 7 in the rhubarb
      treated group, showing significant difference as compared with that in the model
      group (P<0.05); (3) The specific amplified products of t-PA mRNA on day 3 and
      that of PLG mRNA on day 7 in CNS of model group were significantly higher than
      those in the sham operated group and the rhubarb treated group. CONCLUSION:
      Rhubarb could effectively reduce the secondary CNS damage in rats with AHS, it
      might be related with the suppressive effect of rhubarb on tPA mRNA and PLG mRNA
      expression in CNS.

PMID- 15719750
TI  - [Effect of gardenin on gene expression profile in brain of rats with focal
      cerebral ischemia].
AB  - OBJECTIVE: To explore the pharmacologic mechanism of gardenin in treating
      cerebral ischemia, by studying its effect on gene expression profile in brain of
      rats with focal cerebral ischemia (FCI). METHODS: Total RNAs were isolated from
      rats with FCI and those treated with gardenin. The mRNAs were reversely
      transcribed to cDNA with incorporation of fluorescent Cy5- or Cy3-dUTP to prepare
      hybridization probes. The PCR products of 4096 genes were spotted on the chip
      after a serial treatment. The mixed probes were hybridized to the cDNA
      microarray. Axon Genepix 4000B and GenePixPro 3.0 software were used to scan and
      analyze the fluorescent signals. RESULTS: In the group treated with gardenin,
      there were 70 genes had expression profiles different to that in the model group
      in the focal cerebral ischemic brain tissue, in which 68 were up-regulated and 2
      down-regulated. CONCLUSION: Gardenin has regulatory effect on the gene expression
      in rats with focal cerebral ischemia, which elucidates part of the pharmacologic
      mechanism of Qingkailing in molecular level.

PMID- 15719751
TI  - [Study on cardiac gene expression microarray and recipe for activating blood
      circulation and supplementing qi on heart of rats with post-infarction heart
      failure].
AB  - OBJECTIVE: To observe the effect of recipe for activating blood circulation and
      supplementing Qi (RAS) on cardiac functional structure in rats with post
      infarction heart failure (PIHF). METHODS: Rat model of PIHF was established by
      left coronary artery ligation. Left ventricular samples of model rats from
      infarcted or peri-infarcted area were obtained at PIHF formation stage and stable
      stage (10 days and 8 weeks respectively after operation), the total RNA extracted
      and detected using 6 pieces of rat's 40s gene microarray (4096 genes/microarray),
      the data were analyzed using software as Genespring, Treeview, Clustering and
      SOM. Besides, RAS was used to treat the model rats beginning from 4 weeks after
      modeling and lasted for 4 weeks, changes of heart function and cardiac
      coefficient before and after treatment were observed by impedance method with
      Captopril as positive control. RESULTS: (1) Genespring analysis showed thousands
      of genes differential expression (upper or down regulated), including 13 kinds of
      gene involving energy metabolism, myocardial cytoskeleton, fibrosis, etc. which,
      in the infarcted area at heart formation stage were 1086 genes and at the stable
      stage, 724 genes, while in the peri-infarcted area, formation stage 196 genes and
      stable stage 97 genes. (2) After RAS or Captopril treatment, the heart function
      improved significantly, with the stroke volume, cardiac output and cardiac index
      increased significantly (P < 0.01). RAS could also improve the cardiac
      coefficient of model rats, as compared with that in untreated model, P < 0.01,
      compared with that in the sham-operated rats, P < 0.05. CONCLUSION: PIHF is a
      kind of overload heart disease with multiple genes abnormality. RAS could improve
      the heart function and histologic indexes, so as to treat the heart failure.

PMID- 15719752
TI  - [Study on effect of danshensu in directional differentiation of mesenchymal stem
      cells into neuron-like cells].
AB  - OBJECTIVE: To study the effect of Danshensu (DSS) on directional differentiation
      of mesenchymal stem cells (MSC) into neuron-like cells. METHODS: MSC were
      separated from bone marrow with density gradient centrifugation, wall sticking
      screening and amplified in vitro. Flow cytometry was used to monitor the
      expression of surface antigens. DSS contained in non-serum L-DMEM was used to
      induce differentiation of MSC to neuronlike cells, and the effect of DSS when
      different concentration and acting time used was explored. And levels of neuron
      specific enolase (NSE), neurofilament protein (NF-M), nestin, and expression of
      glial fibrillary acidic protein (GFAP) were measured by immunohistochemical
      method. RESULTS: After being propagated and amplified in vitro, MSC were
      positively expressed for CD29, CD44, CD166, and negatively expressed for CD14,
      CD34, CD45, HLA-DR. After induction of DSS, MSC exhibited the typical form of
      perikaryon with pyknotic cell body and prominence projected like that of neuron.
      These cells were positively expressed in NSE, NF-M and nestin, and negatively
      expressed in GFAP. CONCLUSION: DSS could induce differentiation of MSC to neuron
      like cells in vitro, the action is concentration- and time-dependent.

PMID- 15719753
TI  - [Study on effect of radix astragali on injury of cerebral cortex in neonatal rats
      after hypoxia/ischemia brain damage].
AB  - OBJECTIVE: To study the mechanism of injury of cortical nerve cell in the newborn
      with hypoxia/ischemia brain damage (HIBD), and the neuroprotective effect of
      Radix Astragali (RA). METHODS: Neonatal HIBD model rats were established and
      divided into the sham group, the model group and the RA group. Brain of rats
      obtained at different time points after HIBD to conduct histopathological
      examination, neuron death rate count, as well as determination of caspase-3
      (cysteinyl aspartate-specific proteinase-3) protein mRNA expression in cerebral
      cortex by immunohistochemistry, semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) respectively. RESULTS: In the model group,
      caspase-3 mRNA and protein showed an increase at 6 hrs, reached the peak at 24
      hrs, and decreased at 48 hrs after HIBD, on the 5th and 7th day restored to
      baseline level. After being treated by RA, the neuron death rate of ligated side
      was obviously reduced, caspase-3 mRNA and protein expression peak value decreased
      by 45% (mRNA) and 40% - 43% (protein). CONCLUSION: RA shows markedly neuron
      protection in immature brain cortex after HIBD, which is related with the
      inhibition on caspase-3 expression.

PMID- 15719754
TI  - [Experimental study on effect of chemotherapy combined ginsengnoside Rg3 in
      treating pulmonary carcinoma].

PMID- 15719755
TI  - [Effect of xianzhen tablet on content of advanced glycosylation end products
      (AGEs) and mRNA expression of AGE-specific cellular receptor in renal cortex of
      diabetic rats].
AB  - OBJECTIVE: To investigate the effect of Xianzhen tablet (XZT, a Chinese patent
      compound recipe) on advanced glycosylation end products (AGEs) and mRNA
      expression of AGE-specific cellular receptor (RAGE) in renal cortex of diabetic
      rats in order to explore the mechanism of XZT in protecting kidney. METHODS: The
      diabetic rat model with persistent hyperglycemic renal damage was reproduced by
      streptozotocin. Fluorescent assay and RT-PCR were used to determine the content
      of AGEs and expression of RAGE mRNA in renal cortex in model rats, which were
      treated with XZT and controlled by aminoguanidine (AG) administration. RESULTS:
      The relative content of AGEs and RAGE mRNA expression in renal cortex of model
      rats 12 weeks after modeling were significantly higher than those in the normal
      group (P < 0.05), while those in model rats treated by XZT or AG were markedly
      lower than those in non-treated model rats (P < 0.05), the effect of the both
      groups showed insignificant difference (P > 0.05). CONCLUSION: XZT could reduce
      the accumulation of AGEs in renal cortex of diabetic rats, down-regulate the over
      expression of RAGE mRNA, with the effects similar to that of AG, the inhibition
      of XZT on protein non-enzymatic glycosylation might be one of the mechanisms of
      its effect in protecting kidney.

PMID- 15719756
TI  - [Clinical observation on effect of qiangji recipe combined with physical therapy
      in treating ankylosing spondylitis].

PMID- 15719757
TI  - [Clinical observation on treatment of motor neuron diseases by jiweiling
      injection].

PMID- 15719758
TI  - [Systemic inflammatory reaction and its prevention and treatment with integrative
      Chinese and Western medicine].
AB  - The inflammatory reaction is the important pathologic foundation of growth and
      development of many diseases. Previously, anti-pathogen is the chief treating
      principle on infectious diseases, while anti-inflammation is the supplementary
      one. With the deep-going investigation on the effect of inflammatory reaction in
      the pathological process of severe infectious diseases in recent decade,
      especially the advance of concept on systemic inflammatory reaction syndrome
      (SIRS), anti-inflammatory treatment has become the vital link for comprehensive
      intervention therapy of severe infectious disease. Close correlation is also
      presented between numerous non-infectious diseases with systemic inflammatory
      reaction, e.g., atherosclerosis is one kind of inflammatory reaction, there are
      effects of many inflammatory factors on the metabolic process in patients with
      obesity. The regulation of Chinese herbs on inflammatory reaction may be one of
      the well cut-in points of integrative Chinese and Western medical study of anti
      inflammation.

PMID- 15719759
TI  - [Thinking on the assessment of clinical therapeutic effectiveness of TCM].
AB  - How to assess the therapeutic effectiveness of TCM is the focus of this paper,
      the trend of study on standard for therapeutic effectiveness assessment and
      application of standard for disease combined with symptom diagnosis and treatment
      were described. Taking the study on standard for TCM syndrome of Gan as an
      example, the basic principle and existing problem in standard formulation were
      pointed out. The possibility in establishing the therapeutic effectiveness
      assessment system of TCM by using the quantified scale for therapeutic
      effectiveness assessment as a tool, i.e., the theoretical design of the scale
      formation should be in accord with the theories of TCM, and followed with
      scientific measuring principle, based on the sample investigation to establish
      the database of quantified scale, to make sure the scale that having
      corresponding checking process and scoring criteria so as to make the scale
      meeting the need of reliability and validity. It was also pointed owt that the
      scale should be used in combination with the standard for syndrome
      differentiation, thus, the scientific, practical therapeutic effectiveness
      assessment system of TCM could be built up.

PMID- 15719760
TI  - [Visiting National Center for Complementary and Alternative Medicine].

PMID- 15719761
TI  - [Thesis of Dr. Wang Ling-tai on therapeutic mechanism of nourishing shen
      principle in treating chronic hepatitis B].

PMID- 15719762
TI  - [Protective effect and mechanism of ginsenosides on central nerve system of
      animals].
AB  - Progress of studies concerning the protective effect of ginsenoside on central
      nerve system (CNS) in animals and its mechanism published in recent decade were
      reviewed in this paper. It showed that ginsenosides could improve the learning
      capacity and memory in normal, aged animals, as well as in model animals with
      impaired memory. The mechanism of the protective effect on CNS involves the
      effects on calcium channel blockade, glutamate and gamma-aminobutyric acid,
      antiperoxidation, estrogen-like action, nitric oxide and its synthase, also the
      inhibition on cerebral nerve cell apoptosis and amelioration on mitochondrial
      dysfunction, etc.

PMID- 15719763
TI  - [Standard for diagnosis and therapeutic effect evaluation of diabetes mellitus by
      integrative Chinese and Western medicine (draft)].

PMID- 15719764
TI  - [Heart rate variability in Chagas' patients with and without hypertension].

PMID- 15719765
TI  - [Analysis of cardiac autonomic function in hamsters with Chagas disease].

PMID- 15719766
TI  - [Performance analysis of the research of IgG antibodies alive promastigote anti
      forms of Leishmania (V.) braziliensis (AAPV-IgG), for flow cytometry in the
      diagnosis of the leishmaniasis american tegumentar].

PMID- 15719767
TI  - [Epidemiology of leishmaniasis in Goias State, Brazil - 2002].

PMID- 15719768
TI  - [Epidemiological status of visceral leishmaniasis in Goias State, Brazil - 2002].

PMID- 15719769
TI  - [Epidemiological status of american leishmaniasis in Alagoas State, Brazil -
      2002].

PMID- 15719770
TI  - [Epidemiological evaluation of american leishmaniasis in Amapa State, Brazil -
      2002].

PMID- 15719771
TI  - [American leishmaniasis in the state of Sao Paulo: epidemiological status in 2001
      2002].

PMID- 15719772
TI  - [American leishmaniasis in the state of Sao Paulo: epidemiological status in 2001
      2002].

PMID- 15719773
TI  - [Evaluation of a rapid test using recombinant k39 antigen in the diagnosis of
      visceral leishmaniasis in Brazil ].

PMID- 15719774
TI  - [Distribution of cases of human visceral leishmaniasis in Pernambuco, Brazil in
      2002].

PMID- 15719775
TI  - [American leishmaniasis in Mato Grosso do Sul, Brazil].

PMID- 15719776
TI  - [American visceral leishmaniasis in Mato Grosso, Brazil - 2002].

PMID- 15719777
TI  - [American leishmaniasis in Mato Grosso State, Brazil - 2002].

PMID- 15719778
TI  - [Distribution of cases of american leishmaniasis in Pernambuco, Brazil in 2002].

PMID- 15719779
TI  - How pension reform will hit nurses.

PMID- 15719783
TI  - The best years of your life.

PMID- 15719784
TI  - Changing courses.

PMID- 15719785
TI  - Multidisciplinary work to provide cardiac rehabilitation for patients.
AB  - Cardiac rehabilitation is an important aspect of cardiac care strategies. This
      article outlines the importance of such care using a case-study approach to
      highlight the impact that rehabilitation programmes can have on individual
      patients.

PMID- 15719786
TI  - What you need to know about erectile dysfunction.

PMID- 15719787
TI  - Paracetamol.

PMID- 15719788
TI  - Oxygen therapy.

PMID- 15719789
TI  - Understanding nausea and vomiting in advanced cancer.
AB  - Nausea and vomiting are commonly experienced by people with advanced cancer.
      Nausea and vomiting can have an adverse effect on a patient's physical,
      psychological and social well-being. Knowledge of the physiology of nausea and
      vomiting will promote a rational choice of treatment. Nurses also need to be
      aware of non-pharmacological measures that can reduce these distressing symptoms.

PMID- 15719790
TI  - Using guidelines to minimise the hazards of blood transfusion.

PMID- 15719791
TI  - Examining how well students use correct handling procedures.
AB  - AIM: To explore the extent to which undergraduates apply taught principles when
      performing handling and moving activities during practice placements and the
      factors that influence their application. METHOD: A seven-item questionnaire
      comprising closed and open-ended questions was administered to 10 undergraduate
      third-year students, which was followed by a semi-structured interview after they
      had completed their practice placements. RESULTS: This study found that there
      were many situations where students were unable to apply the principles as taught
      in the classroom. The constraints imposed by the combined effects of the
      environment, resources and time limited the application of the safe principles.
      In areas where handling and moving was seen to be an integral part of patient
      management, students were encouraged to use the correct techniques. CONCLUSION:
      The emphasis on educational input in relation to the safe application by students
      of the principles of handling and moving should be to provide a structured
      programme that is consistent with practice on the wards.

PMID- 15719793
TI  - Conservative management of varicose veins.
AB  - Varicose veins occur in approximately 15-20 per cent of the UK population
      (Callam, 1994). Although there is no universally accepted definition of a
      varicose vein, Callam (1999) has described it as 'a superficial vein of the lower
      limb, which has permanently lost its valvular efficiency and, because of the
      resultant venous hypertension caused by the standing position, becomes dilated,
      tortuous and thickened'.

PMID- 15719792
TI  - Heel pressure ulcers and ankle brachial pressure index.
AB  - There is a substantial body of literature that emphasises the importance of
      measuring ankle brachial pressure index (ABPI) as part of an holistic assessment
      for leg ulcers (Scottish Intercollegiate Guideline Network, 1998). However, there
      is a paucity of research-based evidence to indicate the importance of measuring
      ABPI as part of an holistic assessment for patients who develop pressure ulcers
      on their heels. (ABPI is a simple, non-invasive method of identifying arterial
      insufficiency within a limb.) The importance of identifying the presence of
      peripheral vascular disease (PVD) in patients who develop pressure ulcers on
      their heels is discussed, as is the argument for measuring ABPI as part of an
      holistic assessment for heel ulceration before planning the wound management.

PMID- 15719794
TI  - The choice, application and review of topical treatments for skin conditions.
AB  - Topical treatments are essential in the management of skin conditions. However,
      for the nurse working outside the specialty of dermatology, knowing exactly what
      topical treatment to use, and where and when to apply it, can be extremely
      daunting.

PMID- 15719796
TI  - Writing good essays is a lifelong skill.

PMID- 15719795
TI  - Skin hygiene practices, emollient therapy and skin vulnerability.
AB  - The promotion and maintenance of skin integrity is one of the most common
      challenges for nurses in every sphere of practice, but particularly for those
      caring for patients with chronic inflammation of the skin (such as in eczema and
      psoriasis), and to those at risk of skin breakdown due to immobility, circulatory
      disease, or incontinence. A significant amount of nursing time is spent washing
      patients, or assisting them to wash. However, little attention has been given to
      a scientific appraisal or evidence of the effectiveness of these activities.

PMID- 15719797
TI  - [CME EKG 3. Fracture if the tibia].

PMID- 15719798
TI  - [Gene therapy for liver diseases--facts or fiction].
AB  - Molecular analyses have become an integral part of biomedical research as well as
      clinical medicine. The definition of the molecular and genetic basis of many
      human diseases has led to a better understanding of their pathogenesis and has in
      addition offered new perspectives for their diagnosis, treatment and prevention.
      Genetically, human diseases can be classified as hereditary monogenetic, acquired
      monogenetic and acquired complex genetic diseases. Based on this classification,
      gene therapy is based on four concepts: gene repair or substitution, block of
      gene expression (triple helix formation, sense strategy, ribozymes, small
      interfering (si) RNAs and gene augmentation as well as DNA vaccination. While
      recent developments are promising, various delivery, targeting and safety issues
      need to be addressed before gene therapy will enter clinical practice. In the
      future, gene therapy of liver diseases may become part of our patient management
      and complement existing therapeutic strategies.

PMID- 15719799
TI  - [IBSA: chondroitin sulfate--view of light in treatment of finger joint
      arthrosis].

PMID- 15719800
TI  - [Diagnosis of hepatitis B and C].
AB  - Diagnosis of hepatitis B and C is based on sensitive and specific serological
      assays. Molecular assays for the detection of HBV DNA or HCV RNA are in some
      instances needed to confirm the diagnosis. However, their principal role is in
      the therapeutic decision making and in the monitoring of antiviral therapy.

PMID- 15719802
TI  - The changing scenario of diabetes mellitus: from despair to hope.

PMID- 15719801
TI  - [Diagnosis and therapy of inheritable liver diseases: hemochromatisis, Wilson's
      disease and alpha-1-antitrypsin deficiency].
AB  - The recent years have seen significant progress in the area of genetically
      determined liver diseases. For hereditary hemochromatosis, Wilson's disease and
      alpha-1 antitrypsin deficiency the underlying genetic defects have been described
      and well characterized. Although a direct relationship between genetic defect and
      disease manifestation exists genetic test only have a limited diagnostic
      usefulness which requires exact knowledge of the underlying molecular pathology.
      The classical C282Y and H63D mutations of the HFE gene only show a penetrance of
      10-20% in hemochromatosis and are not useful for population screening. Genetic
      screening for ATP7B (Wilson's disease) and alpha-1 antitrypsin deficiency
      variants is limited by the existence of a plethora of individual mutations.
      Genetic tests are mainly restricted to the counseling of families in whom these
      diseases are present. Foremost the diagnosis of the three diseases is reached by
      clinical, biochemical and in some instances also histological means which are
      supplemented and confirmed by the use of appropriate genetic tests.

PMID- 15719803
TI  - Diabetic microvasculopathy: the renal-retinal link.
AB  - Manifestations of diabetic microvasculopathy are protean. Graded increases in the
      severity are recognised in both nephropathy and retinopathy. This study was
      undertaken with 100 patients of type 2 diabetes mellitus to evaluate how far
      these graded increments could be linked at each stage and in each patient. The
      renal parameters studied were the various accepted levels of albuminuria; the
      retinopathy parameters ranged from normal retina to severe proliferative stages.
      Corresponding grades were proposed and altered, if required, to reach the best
      possible correlation. The correlation was attempted though the common link of
      mean glomerular filtation rates at each level and the concordance of either
      parameter grade in an individual patient. The correlations of the mean glomerular
      filtration rate for all propositions of severity were significant. However, there
      was significant variability of the parameters in an individual patient. This was
      more with less severe grades but diminished with increased duration. The
      predictive value of one lesion for the other was low in cases with shorter
      duration and less severe grades. Probably, shorter duration patients have an
      interplay of both genetic factors and the assault of the risk factors while in
      longer duration patients the cumulative risk exposure play the dominant role.

PMID- 15719804
TI  - A study of bone mineral density in diabetes mellitus in eastern India.
AB  - To measure bone mineral density in diabetic patients at the time of clinical
      diagnosis of diabetes mellitus and to find out correlation, if any, with
      microvascular complication of diabetes mellitus and glycosylated haemoglobin, a
      study was conducted at Medical College and Hospital, Kolkata among 138 cases of
      diabetes and 212 controls. All patients were screened for ophthalmoscopy, routine
      blood and urine examinations. Bone ultrasound attenuation study of the calcaneus
      was performed in all cases. The bone ultrasound attenuation result was compared
      to a mean normal population result and expressed as Z score and T score. The age
      of diabetic patients varied from 11 years to 70 years. Of 138 diabetics, 32
      (23.18%) had type 1 diabetes and rest type 2 diabetes. Forty-two diabetic
      patients had retinopathy, 42 nephropathy and 48 had neuropathy. Glycosylated
      haemoglobin was above 7% in 124 patients. The broadband ultrasound attenuation of
      type 1 diabetics ranged from 38 to 95 dB/MHz and in type 2 it was 35 to 104
      dB/MHz. There was no statistically significant correlation between neuropathy,
      nephropathy, retinopathy and bone mineral density status. It was also found no
      correlation between glycosylated haemoglobin values and ultrasound attenuation.

PMID- 15719805
TI  - Prevention of microvascular and macrovascular complications in diabetes mellitus.
AB  - Microvascular and macrovascular complications in relation to diabetes mellitus
      are responsible for major morbidity and mortality condition. Prevention of these
      complications should be the aim while managing diabetes. Retinopathy, nephropathy
      and neuropathy are microvascular complications and macrovascular complication
      affects heart, brain and foot. In preventing retinopathy, glycaemic and blood
      pressure control is essential. Laser photocoagulation therapy can prevent loss of
      vision in non-proliferative or proliferative diabetes mellitus. The aim of
      preventing nephropathy lies on meticulous glycaemic control, dietary protein
      limitation and vigorous control of blood pressure. The highest priority at
      present to prevent diabetic neuropathy is the education of patients and their
      physicians about the potential for detection and treatment of early neuropathy.
      Glycaemic control is beneficial in reducing the frequency of progression of
      neuropathy. Macrovascular complication (cardiovascular, cerebrovascular,
      peripheral vascular) can be prevented with some intervention strategies eg,
      discouraging smoking habit, proper diet, regular physical activity, strict
      glycaemic and blood pressure control, lowering low density lipoprotein
      cholesterol level and aspirin therapy. Amputation in diabetic foot can be dealt
      with a number of prevention strategies eg, careful self examination, to use
      specially fitted shoes, minimisation of trauma, earlier detection and aggressive
      management by local debridement, provision of special support and early
      antibiotic therapy.

PMID- 15719806
TI  - Insulin in type 2 diabetes: promises to keep.
AB  - The concept which has evolved in the management of type 2 diabetes mellitus is
      early insulin therapy. In type 2 diabetes mellitus first phase insulin response
      is grossly impaired on eventually absent, overburdening phase 2 responses which
      obviously fail to compensate in the long run. Perpetuation of the age old
      practice to continue OHA while almost all beta-cells are exhausted is only buying
      time for starting insulin. Preservation of beta-cell function by early insulin
      therapy yields two important benefits: (1) Better glycaemic control at lower
      medication dose and (2) relative freedom from hypoglycaemia because of well
      preserved glucagon response. To ensure and to translate the proper action of
      insulin in the target organs we are now talking about designer insulins which are
      basically insulin analogues (short and long acting). So type 2 diabetes is a
      growing menace and is responsible for severe morbidity, mortality and poor
      quality of life. Good glycaemic control from the very beginning of diabetes has
      shown to favourably influence all of these and is accepted as a cardinal goal of
      proper diabetes care.

PMID- 15719807
TI  - Growth hormone deficiency in children: an approach to a child with short stature.
AB  - The importance of recognition of short stature in a child is very important as it
      allows one to identify important medical conditions where physical shortness is
      only one manifestation. Causes of short stature are: Familial, idiopathic, delay
      in growth and maturation, chronic systemic illnesses, endocrinopathies, rickets,
      skeletal dysplasia, chromosomal disorders and emotional deprivation. Proper
      history, physical examination, endocrine and non-endocrine investigations are
      crucial for arriving at the diagnosis of short stature. The cardinal
      manifestation of growth hormone deficiency in children obviously interferes
      physical growth. Causes of growth hormone deficiency may be congenital or
      acquired. A peak growth hormone level of < 10 microg/l in response to stimulation
      tests along with some clinical features is generally considered sufficient to
      diagnose growth hormone deficiency. Growth hormone in a dose of 25-50
      microg/kg/day should be administered subcutaneously once daily at bed time for
      growth hormone deficiency state.

PMID- 15719808
TI  - Glycaemic consequences of HIV and highly active antiretroviral therapy: a pilot
      study and review of literature.
AB  - The metabolic consequences of HIV and AIDS are accentuated in the setting of
      highly active antiretroviral therapy. Peripheral lipodystrophy, central
      adiposity, hyperlipidaemia, insulin resistance and diabetes mellitus are frequent
      associations of protease inhibitor containing highly active antiretroviral
      therapy regimens. Ninety patients aged 25-50 years (males 52, females 38),
      seropositive for HIV 1 and 2 or both were selected to see the glycaemic profiles
      in asymptomatic early HIV disease with CD4 counts > 100/microl and to compare
      this with the glycaemic profile of (a) advanced HIV disease (CD4 counts <
      200/microl), not on highly active antiretroviral therapy and (b) advanced HIV
      disease (CD4 counts < 200/microl), on uninterrupted non-protease inhibitor highly
      active antiretroviral therapy > 6 months. All the patients were grouped into 3:
      (1) Group A: CD4 counts > 500/microl (n=37), highly active antiretroviral therapy
      naive, (2) group B: CD4 counts < 200/microl (n=21), not on highly active
      antiretroviral therapy, and (3) group C: CD4 counts < 200/microl, receiving
      uninterrupted non-protease inhibitor based highly active antiretroviral therapy
      for > 6 months (n=32). The fasting blood glucose, glycosylated Hb (HbA1c) levels,
      were measured in all the patients in 3 groups and significance of difference
      between means was calculated among various groups. Body weight and waist-hip
      ratio were also measured. The results were analysed and compared with other
      studies.

PMID- 15719809
TI  - No one can eat just one: diet, diseases and the media in a consumerist society.

PMID- 15719810
TI  - Questionnaire on 'diabetes'.

PMID- 15719811
TI  - [Marijuana smoking and paroxysmal atrial fibrillation].
AB  - INTRODUCTION: Cannabis is the most widely used illegal drug in Israel, and unlike
      most of the other illegal drugs, it is common among segments of the population
      with higher demographic characteristics. CASE REPORT: A healthy 20 year old male
      patient, with two previous admissions with atrial fibrillation, was admitted to
      the emergency room with paroxysmal atrial fibrillation. The patient presented
      evidence of cannabis abuse, and no other pathologic cause for atrial
      fibrillation. Sinus rhythm was restored and the patient was discharged.
      DISCUSSION: Cannabis abuse is responsible for a wide range of pathologies,
      including cognitive impairment, a rise in the prevalence of lung, head and neck
      tumors, atrial and ventricular arrhythmias, and an increase in the risk of
      ischemic cardiovascular events. CONCLUSIONS: Cannabis abuse can induce atrial
      fibrillation in predisposed patients. Good practice may consider the inclusion of
      cannabis abuse tests in young patients admitted due to atrial fibrillation, and
      definite medical advice to stop the drug abuse.

PMID- 15719812
TI  - [Biphasic shock waveform for cardioversion of atrial fibrillation in the
      emergency room].
AB  - Transthoracic electrical cardioversion, traditionally monophasic shock waveform,
      has been a mainstay of the therapy for atrial fibrillation (AF) since its
      introduction into clinical practice. Recent studies have demonstrated that
      biphasic shock is more efficient than monophasic shock waveforms for terminating
      both ventricular fibrillation and AF; however, data on the recommended initial
      shock energy in conversion of AF by biphasic shocks are limited. AIM: Our study
      aimed to evaluate the optimal dose of the initial shock energy for conversion of
      AF to sinus rhythm by transthoracic biphasic shock waveforms in the Emergency
      Room (ER). METHODS AND RESULTS: A total of 144 consecutive patients, who came to
      the ER because of AF, were our study population. All patients underwent
      cardioversion via anterior-laterally positioned hand-held electrode paddles.
      Patients received sequential shocks of 50 J (only the first 40 patients), 100 J,
      150 J and 200 J if necessary. There was a significantly greater cumulative
      conversion success rate with 100 J (70.5%) than 50 J shock energy (55%), p <
      0.05; but even greater with 150 J (89%) than 100 J shock energy, p < 0.003; no
      significant difference was observed between 200 J (94%) and 150 J shock energy, p
      < 0.58. Nine of 12 patients, whose body weight was less than 70 kg, were
      successfully converted to sinus rhythm (75%) by 50 J shock 1 energy. After
      cardioversion there were reports of: a five seconds asystole observed in 1
      patient; pulmonary edema in another patient; hypotension was reported in 1
      patient and mild erythema in 14 patients (9.7%). CONCLUSION: Our findings support
      that biphasic waveform shock energy of 150 J is advised as a first attempt, but
      in patients with a body weight less than 70 kg. lower energy shock may be used.

PMID- 15719814
TI  - [Reconstruction of the lips after resection of malignant lesions].
AB  - This review deals with the presently used techniques for reconstruction of full
      thickness lip defects that occur as a result of resection of malignant lesions of
      the lips. Reconstruction of full thickness defects of the lip is not an easy
      task. Since the lips have such centrally important aesthetic and functional
      roles, successful maintenance of these roles after reconstruction is of paramount
      importance. Small defects of up to 1/3 of the lip are normally fairly easily
      reconstructed by means of primary closure, while extremely large defects of
      almost the entire lip will need to be reconstructed by means of distant free
      flaps with microsurgical techniques. We review a broad range of local flaps
      utilized for the reconstruction of full thickness defects greater than 1/3 of the
      lip up to the reconstruction of more than 1/2, but not the entire lip. The
      article presents the advantages and disadvantages of several techniques which are
      currently widely used.

PMID- 15719813
TI  - [Salmonellosis outbreak among first grade schoolchildren, Hadera Subdistrict].
AB  - OBJECTIVES: This article describes an outbreak of salmonella food-borne infection
      in a school in Or-Akiva, Hadera Sub-district, and analyzes the lessons that can
      be learned from the episode. DESIGN: Epidemiological study of the outbreak: A
      retrospective case control study. RESULTS: Forty three of the 89 participants in
      a first grade party became ill with gastroenteritis. The epidemiological
      investigation identified the source of infection in a cream cake. The cake was
      bought from an unlicensed facility where it was prepared and stored at
      inappropriate temperatures. The odds ratio for illness associated with consuming
      the cake was highly significant OR = 43.0 (95% CI = 7.82-313.66). Two patients
      had stool cultures positive for Salmonella enterica (Group D Salmonella).
      CONCLUSION: In order to prevent outbreaks through transmission by fecal-oral
      route, food should be purchased from licensed sources and should be stored at
      appropriate temperatures until consumption.

PMID- 15719815
TI  - [Ultrasonic apocrine suction-lipolysis under endoscopic guidance for axillary
      osmidrosis].
AB  - There are several modalities to treat axillary hyperhydrosis. None of these
      eliminates the sweat-associated odor (Osmidrosis), which is sometimes present
      even despite local hygiene and use of deodorants. A technique to dissolve the
      axillary apocrine glands under endoscopic guidance has been described to be
      highly efficient, without compensatory hyperhydrosis. We describe our experience
      with the first 18 patients who were treated by this technique. A 1.5 cm axillary
      incision was used to introduce both the endoscope and the ultrasonic suction
      lipolysis device. Complete disappearance of axillary sweat and odor was achieved
      immediately after treatment. Superficial hematoma was the only complication
      encountered. One-sided recurrence was observed in one patient over an 8 month
      follow-up period.

PMID- 15719816
TI  - [Anesthesia for aesthetic surgery].
AB  - Anesthesia for aesthetic surgery has changed along with the development in
      plastic surgery during the last two decades. This is the first report of a large
      series of anesthesia conducted for aesthetic surgery in Israel. The article
      presents the experience of ten thousand procedures performed during the last four
      years. Although the prevalence of extensive surgery and complicated patients has
      increased, no anesthetic-related mortality and only minor morbidity have
      occurred. Methods of anesthesia and prevention of complications are described.
      Specific approaches for some potentially dangerous procedures are discussed.

PMID- 15719817
TI  - [A preparatory course for retirement by the Israeli Medical Association].
AB  - OBJECTIVE: Retirement can be traumatic, and physicians are not immune. The
      Israeli Medical Association (IMA) has been conducting a preparatory course for
      retirement for its members reaching retirement. The objective of the present
      study was to survey the characteristics of participating physicians, to map their
      activities following retirement, to gauge their appreciation of the course, and
      to assess their willingness to continue their association with the IMA. METHODS:
      Questionnaires were mailed to 210 attendees of the IMA course in 2000-2002, and
      responses were tabulated and analyzed. RESULTS: The response rate was 33%--40
      male and 30 female physicians, and 75% of them were still working at the time of
      response. They classified their quality-of-life as appropriate (70%), modest
      (2%), and unfitting (27%). Continued work was directly related to the
      preservation of fitting lifestyle (p < 0.0001), and of the 17 physicians not
      working only 4 defined their quality of living as suitable. Of the respondents,
      83% were in good health, 50% needed medical attention, and 77% received proper
      care. The vast majority spent time with family and friends, reading, listening to
      music, going on trips and cultural events and engaged in sports; the minority
      spent time learning, busy with hobbies or volunteer work. Approximately half of
      the respondents attended continuing medical education classes. Much satisfaction
      was recorded for most activities, but television, friends, volunteer work or
      continuing education were only partly enjoyable. The IMA preparatory course was
      satisfactory according to 94% of the respondents, but many requested to broaden
      its scope. Over 92% wanted to maintain an "open-line" with the IMA, for obtaining
      information, counseling, and participation in social activities and continuing
      education. The majority was willing to volunteer in the IMA. No gender bias was
      found in most of the responses. CONCLUSION: This preliminary survey of physician
      retirement in Israel found that once physicians ceased working, many considered
      their life quality unfitting. The need to remain associated with the IMA is
      indicative of the large social and emotional importance of this membership.

PMID- 15719818
TI  - [Lost in translation: the essential role of the physician as a researcher].

PMID- 15719819
TI  - [The difficult child syndrome].
AB  - Many children are referred to the psychiatrist with the title of the "difficult
      child". Behind that popular and nonscientific description hide several major
      psychiatric syndromes, such as attention-deficit hyperactivity disorder,
      disruptive behavior disorders, mood disorders and posttraumatic stress disorder.
      This article reviews the different clinical faces of these disorders, their
      differential diagnoses, comorbidity and prognosis. These disorders are very
      prevalent and have long-term consequences on the process of development of the
      child. Acquaintance with the disorders, early diagnosis and treatment can prevent
      complications and improve the prognosis.

PMID- 15719820
TI  - [Exercise induced rhabdomyolysis--characteristics, mechanisms and treatment].
AB  - Rhabdomyolysis is defined as a syndrome resulting from skeletal muscle injury
      with release of muscle cell contents into the plasma. One of the main causes of
      rhabdomyolysis is eccentric exercise against high resistance. There are
      mechanical as well as metabolic causes in exercise induced rhabdomyolysis. The
      mechanical aspect includes high physical tension on the muscle fiber and the
      metabolic causes include lack of available ATP and disturbance in intracellular
      electrolyte balance, especially calcium. The clinical picture of rhabdomyolysis
      may include muscle soreness, reduction of the range of motion, decreased muscle
      strength, black urine and, in severe cases, acute renal failure. Laboratory
      results may include delayed high levels of muscle enzymes in the plasma,
      myoglobinemia and myoglobinuria, disturbance in blood electrolyte balance, and in
      severe cases, disturbance in coagulatory function and DIC. Compartment syndrome
      may also be part of severe rhabdomyolyis. The main treatment for rhabdomyolysis
      is fluids administration and maintaining urination, in order to preserve renal
      function. In severe compartment syndrome fasciotomy may be necessary. There is a
      wide variability in the severity of rhabdomyolysis. This variability is not
      completely understood but may be related to the level of physical fitness,
      morphometrical characteristics and gender. In order to prevent exercise induced
      rhabdomyolysis, a gradual training program should be maintained providing enough
      recovery time, preserving fluid balance, and avoiding extreme eccentric exercise
      and exercise in high heat load.

PMID- 15719821
TI  - [Update on the treatment of common gastrointestinal malignancies].
AB  - Common gastrointestinal malignancies, including esophageal, gastric, pancreatic
      and colorectal cancer are among the leading causes of cancer morbidity and
      mortality worldwide. Modern surgical techniques, increasing use of endoscopic
      procedures, the use of new chemotherapy regimens and the development of novel
      biological therapies are among the major advances in the treatment of these
      malignancies that were achieved during the last years. In this review we provide
      an update of the current treatment of common gastrointestinal malignancies and
      focus on these recent advances.

PMID- 15719822
TI  - [By the sweat of your brow shall you eat bread: a blessing or a curse?].
AB  - Physical activity is crucial for maintaining normal structure and function of
      metabolic processes and body organs, such as the heart and muscles. Lack of
      regular activity leads to the deterioration of these organs, thereby increasing
      levels of morbidity and mortality. Physical activity is associated with lower
      incidence of total mortality and mortality from heart diseases. It also inhibits
      high blood pressure, diabetes mellitus, colon cancer and probably breast cancer,
      osteoporosis, mental depression, and improves quality of life. While the
      favorable outcomes are usually related to activity level in a dose-response
      pattern, the greatest benefit is observed in the transition from sedentary to
      moderately active lifestyle. Despite possible direct and indirect adverse effects
      of physical activity, the benefits markedly outweigh the risk. In order to
      benefit from physical activity, people should perform activities that involve
      large muscle mass, at moderate intensity, during most of the week, or at least 3
      days/week, for about 30 minutes a day. It is desirable to add strength and
      flexibility exercises. The need for medical screening prior to initiation of
      activity is questionable, and there are no solid recommendations. In the opinion
      of the authors, at all ages people should be aware of whether they possess one or
      more risk factors for cardiovascular disease. Young healthy people free of risk
      factors may start activity, gradually, without special preparations or screening.
      However, men and women above the age of 45 or 50 years, respectively, or younger,
      if a risk factor is present, should consult their family physician or a
      specialist in order to perform relevant screening and obtain instructions on the
      desired nature of recommended physical activity, its length and intensity.

PMID- 15719823
TI  - [Smallpox vaccination techniques: considerations and unresolved issues].
AB  - The smallpox vaccine is the oldest--and was, for 90 years, the only--vaccine
      known to man. Many vaccination techniques have been used over time, with no fewer
      than ten employed during the 20th century alone. In Israel, two main techniques
      were used prior to smallpox eradication in 1978--multiple punctures using a
      standard needle, and jet injection--while most other countries adopted the
      bifurcated needle as the method of choice. Despite the vaccination experience
      gained over time, doubt remains today as to the preferred vaccination technique.
      During 2002, when Israel became the first country to conduct large-scale smallpox
      vaccination in the 21st century, multiple standard needle puncture was adopted as
      the method of choice, while at the same time the bifurcated needle was readopted
      in the United States. The article reviews the various smallpox vaccination
      techniques, the supporting scientific data, and the current lacunae in knowledge
      related to the subject. Together, these factors will most likely influence the
      adoption of a preferred vaccination technique during a smallpox emergency.

PMID- 15719824
TI  - [Eosinophilic pneumonia--challenges in pathogenesis and novel therapeutic
      approach].

PMID- 15719825
TI  - [Evaluation of activity parameters of passionflower dry extract capsules
      according to a "star" model].

PMID- 15719826
TI  - Ranitidine preparations on the Belgian market: a comparative study.
AB  - Ranitidine preparations formulated as tablets and granules were evaluated with
      different tests including in vitro dissolution and assay. Previously the
      analytical methods of these tests were validated according to the guidelines of
      the European network of Official Medicines Control Laboratories (OMCLs). All
      examined products complied to the requirements as described in the European, the
      British and the US Pharmacopoeia and consequently they can be considered as
      pharmaceutically equivalent.

PMID- 15719827
TI  - [Galenique: the adventure of a word].

PMID- 15719828
TI  - [Andromachus, Galen, Dalibour, Sydenham...: eponyms, as witnesses of an history
      of the respective galenicals].

PMID- 15719830
TI  - ['Artificial support in case of hepatic failure'; a report from the Dutch Health
      Council].
AB  - Acute liver failure has a high mortality (40-95%) depending on the cause.
      Emergency liver transplantation is the only way to improve survival: a one-year
      survival of 5o-6o%. In the past, many different modalities of artificial liver
      support have been studied. None of them appeared to be able to improve survival
      compared to maximal intensive care treatment. Two rather recent approaches are
      the development of a bioartificial liver (BAL), charged with billions of porcine
      liver cells, and albumin dialysis (MARS). A signalling report has been sent to
      the Dutch Minister of Health to resume the current position of BAL and MARS in
      the treatment of severe liver failure. The outcome is that no firm conclusions
      can yet be drawn as to the applicability of these modalities. Only two small
      scale controlled clinical trials have been published on the MARS technique and
      the only published large-scale controlled clinical trial of a BAL in acute liver
      failure is not conclusive. On theoretical grounds, BAL treatment has more
      potential than MARS since a BAL will replace not only the failing hepatic
      detoxification but also the synthetic and metabolic functions. So far, no
      evidence has been found for transmission ofporcine pathogens to patients despite
      numerous phase 1 studies of bioartificial livers charged with porcine
      hepatocytes. More well-designed controlled clinical trials are needed. Therefore,
      the Dutch moratorium on xenotransplantation should be revised.

PMID- 15719829
TI  - [Bizarre somatic complaints as a manifestation of schizophrenia].
AB  - Three patients, men aged 50 and 32 and a woman aged 30 years, presented with
      bizarre somatic symptoms, i.e. that are anatomically and physiologically
      impossible. The first patient, for instance, thought that he could only walk
      while holding his forehead back with his hand; the woman thought that the skin of
      her neck and back was disconnected from the underlying tissues. The patients were
      preoccupied with their complaints and could not be convinced that there was no
      organic substrate for their symptoms. The presented patients had coenesthetic
      symptoms of schizophrenia: disturbances in the awareness of their bodily
      integrity. These symptoms occur frequently in patients with schizophrenia, but
      have not received much attention in medical literature. The patient's visit to a
      somatic or general physician is a good opportunity to refer him or her for
      adequate psychiatric treatment.

PMID- 15719831
TI  - [The importance of the National Public Health Compass for public health].
AB  - The National Public Health Compass provides an online overview of the current
      state of public health in the Netherlands. The Compass contains largely the same
      information as the Dutch Public Health Status and Forecasts Reports, the 2002
      edition of which showed stagnation of public health improvement. This highlights
      the role of these overviews in the signalling of public health problems. The
      quality of the reporting on public health has been shown to be high and the
      reports are successful in providing information for Dutch health policy. However,
      if the Dutch are to regain their leading position in Europe, more policy efforts
      are required.

PMID- 15719832
TI  - [Health and disease in the Netherlands: the Dutch National Public Health Compass
      as a source of information].
AB  - --The Dutch National Public Health Compass has been available on the Internet
      (www.nationaalkompas.nl) since 2001. This website, developed and managed by the
      National Institute for Public Health and the Environment, contains data and
      information on the population's health status, its determinants, prevention and
      care. The Compass brings together information from various data sources, research
      and expert opinions. --On the basis of this Compass, an overview has been made of
      the health of the Dutch population. --Both the life expectancy and the healthy
      life expectancy in the Netherlands increased after 1980. --Mortality from
      coronary heart disease, cerebrovascular accidents and lung cancer decreased, but
      they are still the most important causes of death. --Especially psychological
      disorders (alcohol dependence, anxiety disorders and depression), coronary heart
      disease and COPD are associated with a significant decrease in quality of life. -
      There are important health differences in the Netherlands between rich and poor,
      urban and rural areas, natives and immigrants. --The difference in life
      expectancy between men and women will decrease from more than 5 years in 2000 to
      less than 4 years in 2020. --A permanent facility for the provision of accurate
      public-health information is of great importance. The collaboration of
      registration holders and experts in maintaining the Compass is and will remain
      essential so that an integral overview of the health of the Dutch population can
      also be made in the future.

PMID- 15719833
TI  - [The wider application of photodynamic therapy in dermatology].
AB  - Photodynamic treatment is increasingly employed in the detection and treatment of
      malignant and non-malignant skin disease. --Indications for photodynamic therapy
      so far are actinic keratosis, Bowen's disease and superficially growing basal
      cell carcinomas, and probably verrucae and acne vulgaris. --This technology is
      also currently under investigation for fluorescence diagnostics oftumour margins.
      --The exact position of photodynamic therapy has not yet been established because
      there are too less long-term comparative studies demonstrating its effectiveness.
      --Based on the short-term results, photodynamic therapy deserves a place within
      the total therapeutic arsenal of the dermatologist of today for the indications
      mentioned above.

PMID- 15719834
TI  - [The treatment of patients with gastric carcinoma based on the results of Dutch
      studies].
AB  - --The extent of lymph-node dissection in gastrectomy for gastric carcinoma and
      the use of adjuvant or neo-adjuvant chemotherapy is a matter still under
      discussion. Only radical resection can offer a cure. --Non-randomised studies
      show that extended lymph-node dissections are more advantageous than less
      extended dissections. None of the randomised trials confirms this. The associated
      statistically significant higher morbidity and mortality offsets its long-term
      advantageous effect on survival. --If procedures that increase morbidity and
      mortality such as pancreatectomy and splenectomy can be avoided, then extended
      lymph-node dissections are more advantageous. --In cases of inadequate dissection
      (i.e. less than 15 lymph nodes removed) adjuvant radiochemotherapy confers an
      advantage. If adequate dissection is carried out, this advantage is not present. 
      -To date there is no indication for adjuvant or neo-adjuvant chemotherapy. --To
      improve the results of treatment for gastric carcinoma in Western countries and
      to simplify trial participation, treatment for patients with gastric carcinoma
      should be centralised.

PMID- 15719835
TI  - [Diagnostic image (225). A woman with extensive necrosis of the abdominal skin].
AB  - In a 6o-year-old woman suffering from end-stage renal disease and diabetes,
      progressive ulceration of the abdominal skin and subcutaneous soft tissues
      occurred due to calciphylaxis.

PMID- 15719836
TI  - [Non-incarcerated inguinal hernia in children: operation within 7 days not
      necessary].
AB  - OBJECTIVE: To assess the necessity to operate on non-incarcerated inguinal hernia
      in children within 7 days of diagnosis. DESIGN: Retrospective. METHOD: Data on
      360 children, 0-10 years old (104 girls and 256 boys) who were operated on for
      inguinal hernia between 1 January 1993-31 December 2001 at the St. Elisabeth
      Hospital in Tilburg, the Netherlands, were collected from the medical records.
      These data included sex, age, interval between diagnosis and repair, recurrence,
      incarceration, length of hospitalisation and complications. RESULTS: In the group
      of 113 children 0-1 years old, 137 inguinal hernias were repaired, ofwhich 16
      were incarcerated on presentation. The interval between diagnosis and repair was
      known in 93 of 121 cases: 37 hernias were repaired within 7 days and 56 at a
      later stage. In the latter group, there was one case of secondary incarceration
      (1.8%; 95% CI: 0-5.4). The number needed to treat was 56. In the group of 247
      children 1-10 years old, 269 inguinal hernias were repaired, of which 8 were
      primarily incarcerated. The interval between diagnosis and repair was known in
      208 of 261 cases: 34 hernias were repaired within 7 days and 174 at a later
      stage. In the latter group, 3 hernias incarcerated secondarily (1.7%; 95% CI: 0
      3.7). The number needed to treat was 58. In the group of non-incarcerated hernias
      1 complication occurred, in the group of incarcerated hernias none. The mean
      length of hospitalisation of children with non-incarcerated hernia was 0.85 days,
      and of children with incarcerated hernia 2.4 days. CONCLUSION: In children with a
      non-incarcerated inguinal hernia who are waiting for an operation, the risk of
      secondary incarceration and complications is 2% which we do not think is enough
      reason to carry out an elective hernia-repair procedure within 7 days.

PMID- 15719837
TI  - [Multidisciplinary approach to patients with persistent swallowing problems; the
      first experiences, 1996/'02 in Louvain].
AB  - OBJECTIVE: To inventory the experiences of a multidisciplinary team for the
      treatment of patients with chronic swallowing problems. DESIGN: Descriptive,
      retrospective. METHOD: Data were collected on the cause, treatment and course in
      400 consecutive ambulatory patients who had had swallowing problems for at least
      several months. During the period from 1 October 1996 to 30 April 2002 they had
      been referred to a multidisciplinary team consisting of a radiologist, an
      otorhinolaryngologist, a thoracic surgeon, a logopaedician, a neurologist and an
      internist-geriatrician in the University Hospitals of the Catholic University of
      Louvain (Belgium). RESULTS: The group of 4oo patients consisted of 236 men and
      164 women, one-third of whom were 70 years of age or older. Half of the patients
      had problems swallowing solid food and more than 10% were unable to take any food
      by mouth. Most of the underlying conditions were neurological. The most commonly
      prescribed treatments were adjustments to the diet and posture (41%) and
      logopaedic guidance (36%). The safety and comfort of swallowing were improved in
      44% of the patients, 13% were able to feed themselves orally once more after the
      intervention and in 11% there was still an indication for a percutaneous
      endoscopic gastrostomy (PEG) catheter.

PMID- 15719838
TI  - [Seizures in foreign newborns due to maternal vitamin-D deficiency].
AB  - In a Moroccan male, a Turkish female and a Sudanese male newborn who presented
      with seizures in the second week of life, hypocalcaemia was found. The
      hypocalcaemia was caused by neonatal vitamin-D deficiency as a result of maternal
      vitamin-D deficiency during pregnancy. The vitamin-D deficiency of the mothers
      was caused by the diminished exposure to sunlight as a result of wearing a veil
      and the dark pigmentation of the skin. The infants were cured by vitamin-D
      suppletion. With the increasing numbers of dark-skinned women and women who wear
      veils in the Dutch population, the group of pregnant women and newborns running a
      risk of vitamin-D deficiency is becoming larger. Therefore, the risk of
      hypocalcaemia and vitamin-D deficiency rickets in newborns is also increasing. In
      newborns with seizures, one should think of the possibility of neonatal vitamin-D
      deficiency, especially if the mothers belong to the group at risk.

PMID- 15719839
TI  - [Still no proof of the efficacy of acupuncture in the prevention of migraine].

PMID- 15719840
TI  - [The acute compartment syndrome of the arm].

PMID- 15719841
TI  - [Missed acute compartment syndrome of the lower leg].

PMID- 15719842
TI  - [Turning the head, an unusual mechanism to compensate for diplopia caused by
      abduction restriction of one eye].

PMID- 15719843
TI  - [Turning the head, an unusual mechanism to compensate for diplopia caused by
      abduction restriction of one eye].

PMID- 15719844
TI  - [Turning the head, an unusual mechanism to compensate for diplopia caused by
      abduction restriction of one eye].

PMID- 15719845
TI  - Gene therapy for genetic lipid disorders: lipoprotein lipase deficiency as a
      paradigm.

PMID- 15719846
TI  - Vasopressin: physiology and clinical use in patients with vasodilatory shock: a
      review.
AB  - Vasopressin is a nonapeptide synthesised in the hypothalamus and released upon
      stimulations such as hyperosmolality, hypotension and hypovolaemia. In acute
      shock states serum vasopressin levels increase rapidly and decrease in prolonged
      septic shock. The administration of vasopressin in healthy subjects has little
      effect, whereas in vasodilatory shock it increases the mean arterial pressure
      through V1 receptors and decreases the cardiac output. Vasopressin stimulates the
      V2 receptors in the kidney leading to reabsorption of water through aquaporin 2.
      However, in vasodilatory shock the antidiuretic effects are overcome by the
      effect vasopressin has on the kidneys: improvement of renal blood flow leading to
      water excretion. Twenty-four studies on the use of vasopressin in patients with
      vasodilatory shock are reviewed. They show that vasopressin potentiates
      norepinephrine effects, increases blood pressure significantly in patients with
      vasodilatory shock and may improve renal function. Side effects ranging from
      ischaemic skin lesions to possible intestinal ischaemia should not be
      underestimated. Above a dose of 0.04 U/min it may lead to cardiac arrest. Effects
      on mortality cannot be interpreted from these studies. Broad clinical use should
      await controlled trials to clarify its effects on clinical outcomes such as organ
      failure and mortality.

PMID- 15719847
TI  - Gene therapy for genetic lipoprotein lipase deficiency: from promise to practice.
AB  - Lipoprotein lipase (LPL) deficiency is a rare, hereditary disorder of lipoprotein
      metabolism characterised by severely increased triglyceride levels, and
      associated with an increased risk for pancreatitis. Since no adequate treatment
      modality is available for this disorder, we set out to develop an LPL gene
      therapy protocol. This paper focuses on the clinical presentation of LPL
      deficiency, summarises the preclinical investigations in animal models and
      describes the rationale to evaluate gene therapy for this monogenetic disorder of
      lipid metabolism in humans.

PMID- 15719848
TI  - Endovascular stenting in neoplastic superior vena cava syndrome prior to
      chemotherapy or radiotherapy.
AB  - BACKGROUND: The standard conventional palliative treatment of choice for patients
      with neoplastic superior vena cava syndrome (SVCS) is chemotherapy, radiotherapy
      or surgery. In our study, palliative stenting was used as a first-line
      therapeutic measure in all cases using self-expanding stents prior to any
      antitumour therapy. METHODS: 17 patients, 10 men and 7 women, all of whom
      presenting with the clinical diagnosis of SVCS confirmed by phlebography combined
      with CT, were referred for stenting of the superior caval vein. All procedures
      were performed after local anaesthesia without sedatives or general anaesthesia
      in the angiosuite at the radiology department. Symptom response was evaluated
      directly after the procedure at several intervals by clinical and nursing staff.
      RESULTS: 19 self-expanding Symphony stents were successfully implanted in 15 of
      17 cancer patients with SVCS in a period of five years. All 15 individuals
      remained free from SVCS after the successful stenting procedure. No stent-related
      complications occurred. CONCLUSION: This study demonstrates that palliative SVC
      stenting prior to any antitumour therapy is feasible, easily performed without
      serious complications and provides a quicker symptom response than obtained with
      radiation therapy or chemotherapy alone. Primary stenting also provides the
      opportunity to establish a correct diagnosis before starting antitumour therapy.

PMID- 15719849
TI  - Antibiotic control measures in Dutch secondary care hospitals.
AB  - Control measures for the use of antibiotics are essential because of the
      potential harmful consequences of side effects. Various methods have been
      developed to help curb undesirable antibiotic prescription. We performed a survey
      in Dutch secondary care hospitals (response rate 73%) to make an inventory of
      these measures and elucidate possible shortcomings. Almost every hospital was
      using an antibiotic formulary (97%), sometimes supported by extra restrictions in
      antibiotic choice (55%). Local practice guidelines (95%) were commonly present,
      but effective implementation, for example using intranet applications, could be
      improved (21%). National guidelines had received little attention in the
      composition process of local guidelines (19%). Other measures such as educational
      programmes for specialists (11%) and feedback on antibiotic prescription (52%)
      remained largely underused, although their effective implementation may optimise
      antibiotic prescription in hospitals.

PMID- 15719850
TI  - Stridor and Horner's syndrome, weeks after attempted right subclavian vein
      cannulation.
AB  - A 23-year-old woman presented with renal failure resulting from polycystic kidney
      disease (PKD) aggravated by tubulo-interstitial nephritis. Emergency
      haemodialysis was planned, and cannulation of the right subclavian vein was
      attempted, but failed. During this procedure, inadvertent arterial puncture
      occurred. Transient mild ischaemia of the right arm, and a transient Horner's
      syndrome were noted. Seven weeks later she presented with severe stridor with
      impending respiratory failure necessitating emergency intubation; the right-sided
      Horner's syndrome had recurred. CT imaging showed a large pseudo-aneurysm of the
      brachiocephalic artery resulting in severe compression of the trachea. Using a
      prosthetic graft, the operation for the pseudo-aneurysm was successful; there
      were mild neurological sequelae. Although her family history was negative,
      autosomal dominant PKD should be considered, and we discuss the possible role of
      a pre-existing PKD-associated aneurysm.

PMID- 15719851
TI  - Severe hypocalcaemia associated with extensive osteoblastic metastases in a
      patient with prostate cancer.
AB  - A patient with an untreated carcinoma of the prostate was admitted with
      dehydration, stupor and a surprisingly deep hypocalcaemia. The severe
      hypocalcaemia was largely attributed to extensive osteoblastic activity due to
      widespread skeletal metastases although contributing factors to the severity of
      the hypocalcaemia were a relative vitamin D deficiency, hypomagnesaemia and renal
      impairment, preventing the mounting of an adequate homeostatic response. There
      was significant clinical and biochemical improvement after antitumour treatment
      using androgen deprivation, and supplementation with calcium and vitamin D.

PMID- 15719852
TI  - Malaise, anorexia, progressive limb paresis and multiple defects in the kidneys.

PMID- 15719853
TI  - Approach to the patient with gastrointestinal bleeding and anticoagulation.

PMID- 15719854
TI  - Dose calculation and medication error--why are we still weakened by strengths?

PMID- 15719855
TI  - Comparison of the analgesic efficacy and plasma concentrations of high-dose intra
      articular and intramuscular morphine for knee arthroscopy.
AB  - BACKGROUND AND OBJECTIVE: It is important to provide good postoperative analgesia
      after discharge from day case surgery. The usefulness of intra-articular morphine
      for analgesia after day case knee arthroscopy remains controversial. A large dose
      of morphine intra-articularly may provide a good long-lasting analgesia, but its
      efficacy and pharmacokinetics are not known and may be no better than
      intramuscular morphine. We compared the effect of 10 mg intra-articular and
      intramuscular morphine for 24 h post-injection in a randomized double-blind
      study. METHODS: Forty adults undergoing knee arthroscopy were recruited and
      received either 10mg morphine intra-articularly or intramuscularly. Our primary
      outcome was overall visual analogue assessment of pain (0-100 mm scale where 0 is
      no pain and 100 is worst possible pain) between 4 h (on discharge) and 24 h (post
      operatively). Plasma morphine concentrations were measured at 15 min, and 1, 2, 4
      and 24 h. The use of additional analgesia was noted. RESULTS: The assessment of
      pain experienced between discharge (4 h) and 24 h was significantly better in the
      intra-articular (n = 20; mean+/-SD: 18+/-19) than the intramuscular (n = 19;
      mean+/-SD: 34+/-20) group (P = 0.027). The number of patients consuming any
      additional analgesia between discharge and 24 h was significantly lower in the
      intra-articular morphine group (P = 0.038), with 4 (20%) patients in the intra
      articular group and 11 (60%) patients in the intramuscular group consuming
      supplementary analgesia. There were no differences in plasma morphine
      concentrations between the groups. CONCLUSIONS: A large dose of intra-articular
      morphine provided better analgesia than the same dose of intramuscular morphine,
      low plasma morphine levels suggesting a peripheral mechanism.

PMID- 15719856
TI  - Positive end-expiratory pressure applied to the dependent lung during one-lung
      ventilation improves oxygenation and respiratory mechanics in patients with high
      FEV1.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to test the efficacy of
      positive end-expiratory pressure (PEEP) to the dependent lung during one-lung
      ventilation, taking into consideration underlying lung function in order to
      select responders to PEEP. METHODS: Forty-six patients undergoing open-chest
      thoracic surgical procedures were studied in an operating room of a university
      hospital. Patients were randomized to receive zero end-expiratory pressure (ZEEP)
      or 10 cmH2O of PEEP to the dependent lung during one-lung ventilation in lateral
      decubitus. The patients were stratified according to preoperative forced
      expiratory volume in 1 s (FEV1) as an indicator of lung function (below or above
      72%). Oxygenation was measured in the supine position, in the lateral decubitus
      with an open chest, and after 20 min of ZEEP or PEEP. The respiratory system
      pressure-volume curve of the dependent hemithorax was measured in supine and open
      chest lateral decubitus positions with a super-syringe. RESULTS: Application of
      10 cmH2O of PEEP resulted in a significant increase in PaO2 (P < 0.05). This did
      not occur in ZEEP group, considered as a time matched control. PEEP improved
      oxygenation only in patients with high FEV1 (from 11.6+/-4.8 to 15.3+/-7.1 kPa, P
      < 0.05). There was no significant change in the low FEV1 group. Dependent
      hemithorax compliance decreased in lateral decubitus, more in patients with high
      FEV1 (P < 0.05). PEEP improved compliance to a greater extent in patients with
      high FEV1 (from 33.6+/-3.6 to 48.4+/-3.9 mLcmH2O(-1), P < 0.05). CONCLUSIONS:
      During one-lung ventilation in lateral decubitus, PEEP applied to the dependent
      lung significantly improves oxygenation and respiratory mechanics in patients
      with rather normal lungs as assessed by high FEV1.

PMID- 15719858
TI  - Cardiopulmonary bypass induces significant platelet activation in children
      undergoing open-heart surgery.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the effects of cardiopulmonary bypass
      (CPB) on platelet function in children undergoing open-heart surgery. METHODS:
      Data from 16 consecutive children undergoing cardiac surgery with CPB were
      prospectively collected. Blood samples of 10 mL were collected via the central
      venous line immediately before and after CPB for CD62 measurements by flow
      cytometry. RESULTS: Ten children had acyanotic heart disease (median age 3 yr,
      range 1.8-14) and six had a cyanotic defect (median age 4yr, range 2-14). The
      platelet count decreased significantly with CPB in both groups: from 163.5 (130
      201) to 93.5 (57-186) x 10(3) microL(-1) in acyanotic children and from 139.5 (77
      212) to 75 (43-99) x 10(3) microL(-1) in cyanotic children (P < 0.0001). The
      percentage of activated platelets was significantly lower in acyanotic children
      at baseline: 1% (0-23%) vs. 5% (3-8%) (P = 0.07). CPB increased the percentage of
      activated platelets significantly in both groups: post-bypass the values were 10%
      (range 1-17%) in acyanotic children and 7% (range 1-30%) in cyanotic children (P
      = 0.03). The increase in the percentage of activated platelets did not differ
      between the two study groups (P = 0.11). CONCLUSION: CPB induces significant
      platelet activation in children undergoing open-heart surgery.

PMID- 15719857
TI  - Cardiac function and haemodynamics during transition to high-frequency
      oscillatory ventilation.
AB  - BACKGROUND AND OBJECTIVE: This prospective observational study analyses
      cardiovascular changes in adult patients with acute respiratory distress syndrome
      (ARDS) during transition from pressure-controlled ventilation to high-frequency
      oscillatory ventilation (HFOV), using transoesophageal echocardiography (TOE) and
      invasive haemodynamic monitoring. METHODS: Nine patients (median age 65 years;
      range 42-70) with ARDS were studied. HFOV was started and maintained with an
      adjusted mean airway pressure of 5 cmH2O above the last measured mean airway
      pressure during pressure-controlled ventilation. Haemodynamic and TOE
      measurements were performed in end-expiration during baseline pressure-controlled
      ventilation, and again 5 and 30 min after the start of during uninterrupted HFOV.
      RESULTS: Right atrial pressure increased immediately (P = 0.004). After 30 min,
      pulmonary arterial occlusion pressure increased (P = 0.008), cardiac index
      decreased (P = 0.01), stroke volume index decreased (P = 0.02) and both left
      ventricular end-diastolic and end-systolic area indices decreased (P = 0.02).
      Fractional area change, left ventricular end-systolic wall stress, heart rate,
      mean arterial pressure and mean pulmonary artery pressure remained unchanged.
      CONCLUSIONS: Transition to HFOV at a mean airway pressure of 5 cmH2O above that
      during pressure-controlled ventilation induced significant, but clinically minor,
      haemodynamic effects, which are most probably due to airway pressure-related
      preload reduction.

PMID- 15719859
TI  - Comparison of the effects of dexmedetomidine and esmolol on myocardial oxygen
      consumption in dogs.
AB  - BACKGROUND AND OBJECTIVE: The beta-adrenergic blocker esmolol and the alpha 2
      adrenergic agonist dexmedetomidine have the potential to decrease perioperative
      myocardial ischaemia. The pathophysiological mechanisms involved in these anti
      ischaemic properties have not been thoroughly studied. We compared the effects of
      esmolol and dexmedetomidine on two indices of overall myocardial oxygen demand
      and on directly measured myocardial oxygen consumption of the left anterior
      coronary artery territory. METHODS: Eleven mongrel dogs were instrumented to
      measure aortic and left ventricular pressure, aortic and left anterior coronary
      artery flow and myocardial wall thickening. Variables related to myocardial
      oxygen metabolism were also determined. Measurements were performed during four
      sequential experimental conditions in each dog (Control 1: esmolol; Control 2:
      dexmedetomidine). RESULTS: Esmolol and dexmedetomidine decreased haemodynamic
      indices of myocardial oxygen demand to a similar extent: esmolol decreased the
      rate-pressure product by 16+/-3% and the pressure-work index (PWI) by 16+/-3%,
      dexmedetomidine decreased the rate-pressure product by 26+/-3% and the PWI by
      16+/-7%. However, these similar decreases resulted from different haemodynamic
      effects of the two study drugs. Dexmedetomidine had a more pronounced bradycardic
      effect than esmolol (P = 0.01) and increased systolic aortic pressure (SAP) by
      15+/-4% while esmolol decreased SAP by 8+/-2% (P < 0.01). dP/dt(max) and regional
      myocardial area decrease were lower after esmolol than after dexmedetomidine.
      Neither drug had an effect on myocardial oxygen consumption. CONCLUSIONS: Esmolol
      and dexmedetomidine decreased two haemodynamic indices of overall myocardial
      oxygen demand to a similar extent but neither drug decreased directly measured
      myocardial oxygen consumption in the territory of the left anterior descending
      artery.

PMID- 15719860
TI  - The effect of lidocaine on neutrophil CD11b/CD18 and endothelial ICAM-1
      expression and IL-1beta concentrations induced by hypoxia-reoxygenation.
AB  - BACKGROUND: Lidocaine has actions potentially of benefit during ischaemia
      reperfusion. Neutrophils and endothelial cells have an important role in
      ischaemia-reperfusion injury. METHODS: Isolated human neutrophil CD11b and CD18,
      and human umbilical vein endothelial cell (HUVEC) ICAM-1 expression and
      supernatant IL-1beta concentrations in response to hypoxia-reoxygenation were
      studied in the presence or absence of different concentrations of lidocaine
      (0.005, 0.05 and 0.5 mg mL(-1)). Adhesion molecule expression was quantified by
      flow cytometry and IL- 1beta concentrations by ELISA. Differences were assessed
      with analysis of variance and Student-Newman-Keuls as appropriate. Data are
      presented as mean+/-SD. RESULTS: Exposure to hypoxia-reoxygenation increased
      neutrophil CD11b (94.33+/-40.65 vs. 34.32+/-6.83 mean channel fluorescence (MCF),
      P = 0.02), CD18 (109.84+/-35.44 vs. 59.05+/-6.71 MCF, P = 0.03) and endothelial
      ICAM-1 (146.62+/-16.78 vs. 47.29+/-9.85 MCF, P < 0.001) expression compared to
      normoxia. Neutrophil CD18 expression on exposure to hypoxia-reoxygenation was
      less in lidocaine (0.005 mg mL(-1)) treated cells compared to control (71.07+/
      10.14 vs. 109.84+/-35.44 MCF, P = 0.03). Endothelial ICAM-1 expression on
      exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL(-1)) treated
      cells compared to control (133.25+/-16.05 vs. 146.62+/-16.78 MCF, P = 0.03).
      Hypoxia-reoxygenation increased HUVEC supernatant IL-1beta concentrations
      compared to normoxia (3.41+/-0.36 vs. 2.65+/-0.21 pg mL(-1), P = 0.02).
      Endothelial supernatant IL-1beta concentrations in lidocaine-treated HUVECs were
      similar to controls. CONCLUSIONS: Lidocaine at clinically relevant concentrations
      decreased neutrophil CD18 and endothelial ICAM-1 expression but not endothelial
      IL-1beta concentrations.

PMID- 15719861
TI  - The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil
      and endothelial function.
AB  - BACKGROUND AND OBJECTIVE: An acute inflammatory response associated with cerebral
      ischaemia-reperfusion contributes to the development of brain injury. Aprotinin
      has potential, though unexplained, neuroprotective effects in patients undergoing
      cardiac surgery. METHODS: Human neutrophil CD11 b/CD18, endothelial cell
      intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin
      (IL)-1beta supernatant concentrations in response to in vitro hypoxia
      reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(
      1)). Adhesion molecule expression was quantified using flow cytometry and IL
      1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed
      using ANOVA and post hoc Student-Newman-Keuls test as appropriate. RESULTS:
      Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to
      normoxia (170+/-46% vs. 91+/-27%, P = 0.001) (percent intensity of fluorescence
      compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of
      CD11b expression in controls compared to aprotinin-treated neutrophils [(170+/
      46% vs. 129+/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased
      endothelial cell ICAM-1 expression (155+/-3.7 vs. 43+/-21 mean channel
      fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to
      normoxia (3.4+/-0.4 vs. 2.6+/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation
      produced greater upregulation of ICAM- 1 expression [(155+/-3.3 vs. 116+/-0.7) (P
      = 0.001)] and IL-1beta supernatant concentrations [(3.4+/-0.3 vs. 2.6+/-0.1) (P =
      0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n
      = 3). CONCLUSIONS: Hypoxia-reoxygenation-induced upregulation of neutrophil
      CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is
      decreased by aprotinin at clinically relevant concentrations.

PMID- 15719862
TI  - Significance of continuous blood gas monitoring in cardiac surgery with
      cardiopulmonary bypass.

PMID- 15719864
TI  - Continuous infusion of factor VIIIc during heart surgery in a patient with
      haemophilia A.

PMID- 15719863
TI  - A new cardiopulmonary bypass circuit with reduced foreign surface (CorX): initial
      clinical experience and implications for anaesthesia management.

PMID- 15719866
TI  - Checking anaesthetic equipment.

PMID- 15719865
TI  - Heart failure after Caesarean section for twin delivery.

PMID- 15719867
TI  - An overview of controlled studies of anxiety disorders treatment in children and
      adolescents.
AB  - OBJECTIVE: Although several treatments for children and adolescents with anxiety
      disorders are available, there are few well-controlled studies in the literature
      that compare these treatments for efficacy. The objective of this paper is to
      provide an overview of controlled treatment studies for children and adolescents
      with anxiety disorders. METHOD: The research literature on controlled treatment
      studies of anxiety disorders in children and adolescents was systematically
      reviewed through a search of PsycINFO and Medline. Studies that did not compare
      the efficacy of treatment modalities were excluded. RESULTS: This review focuses
      specifically on three main treatment modalities: cognitive-behavioral therapy,
      both individual and group; family-based interventions; and pharmacotherapy. Each
      of these modalities is reviewed in the context of the separate disorders as
      defined by DSM-III-R and/or DSM-IV. The results are especially promising for
      cognitive-behavioral therapy and pharmacotherapy for many of the anxiety
      disorders; however, there are concerns about small sample sizes, lack of
      described comorbidity within the groups and generalizability. CONCLUSION: While
      great strides have been made in the treatment of child and adolescent anxiety
      disorders, empirically based studies are quantitatively limited. More research is
      needed involving head-to-head trials of the different modalities.

PMID- 15719868
TI  - Reducing and eliminating health disparities: a targeted approach.
AB  - Health disparities have dominated recent discourse among public health and
      medical researchers. Ever since the United States began to compile health
      statistics, differences in health status have been noted between majority and non
      majority populations. Myriad approaches have been undertaken in an attempt to
      reduce or eliminate racial and ethnic disparities in health. However, the
      disparities continue to persist. We are at a point in our history where
      innovative strategies must be explored that will be more effective in addressing
      racial and ethnic disparities in health. In large part, health disparities exist
      as a result of inequitable distribution of goods, resources, services and power
      in America. We have learned that improvements in health cannot come about solely
      through primary and secondary interventions but rather through an examination of
      the availability of resources that would allow individuals to improve their
      health. The goal of this paper is to provide an overview of the contextual
      factors that affect health disparities, to integrate theory to address
      disparities and to provide recommendations to encourage systematic changes to
      eliminate health disparities. It is hoped that this paper will bring about a
      national discussion relating to addressing the real issues we face in reducing
      and ultimately eliminating health disparities.

PMID- 15719869
TI  - African-American women's perceptions of their most serious health problems.
AB  - African Americans experience a disproportionate burden of illness. According to
      the Centers for Disease Control and Prevention (CDC), heart disease, cancer,
      cerebrovascular disease and diabetes are the most common causes of mortality
      among African Americans. Data were gathered from 1,055 African-American women to
      gain their perspectives of the most serious health problems affecting African
      American women and their related knowledge, attitudes and health promoting
      behaviors. Women listed CDC's top four causes of mortality as their top four most
      serious health threats. Cancer was reported as a serious health threat by 81% of
      the participants, whereas heart disease, the most common cause of mortality and a
      disease amenable to prevention and early intervention, was mentioned by only 31%
      of the women. Diabetes was reported by 59% of the women and cerebrovascular
      disease by 52%. As the Health Belief and other theoretical models would predict,
      awareness of the seriousness of these four disease groups among African-American
      women was associated with a greater likelihood of adherence for several of the
      recommended behaviors. Many opportunities exist for raising women's awareness of
      these four diseases and linking women's growing health awareness with those
      health promoting behaviors known to reduce morbidity and mortality.

PMID- 15719870
TI  - Left ventricular diastolic function parameters in hypertensives.
AB  - BACKGROUND: Hypertension is associated with left ventricular diastolic function
      abnormalities. There have been few studies evaluating left ventricular diastolic
      function in an African populace. MATERIALS AND METHODS: Ninety-eight
      hypertensives (52 females, 46 males) and 99 normal controls (49 females, 50
      males) were recruited for echocardiography. M-mode measurements and Doppler
      measurements of Mitral inflow and pulmonary venous flow were taken. RESULTS: The
      hypertensives had significantly larger left ventricular wall thicknesses than the
      controls PWT: 0.93 (0.214) vs. 0.88 (0.130), p=0.039: septum: 0.93 (0.255) vs.
      0.87 (0.131), p=0.039. The left ventricular mass indexed to the allometric power
      of height was larger in the hypertensives than in the controls. The Doppler
      parameters of peak A-wave velocity, E/A ratio, deceleration time, peak pulmonary
      venous S-wave, peak pulmonary venous D-wave, S/D ratio and peak pulmonary reverse
      flow velocity were significantly different between the hypertensives and the
      controls. The major determinant of left ventricular diastolic function parameters
      were age and the duration of hypertension. The level of the systolic blood
      pressure, left atrial size and ejection fraction are less important determinants.
      CONCLUSION: Nigerian hypertensives have significantly different diastolic
      function indices when compared with normal controls.

PMID- 15719871
TI  - Racial/ethnic attitudes towards HIV testing in the primary care setting.
AB  - PURPOSE: To determine attitudes of patients towards routine HIV testing in the
      primary care setting. METHODS: Cross-sectional survey on the risk factors,
      beliefs, attitudes and knowledge of HIV/AIDS administered to 101 individuals
      present in urban primary care clinics in Providence, RI. RESULTS: Previous HIV
      testing was done most frequently for those respondents requiring prenatal
      services and for those who were curious about their HIV status. Patients'
      perceptions of their personal risk for HIV infection and their self-identified
      risk factors were frequently discordant. Patients wanted to be tested routinely
      for HIV by their primary care providers, even when they did not feel that they
      were at high risk for HIV acquisition. CONCLUSIONS: Patients in this study
      clearly indicated their desire to be tested for HIV routinely by their primary
      care providers. Routine HIV testing is a reasonable option to identify HIV
      infections in the primary care setting, as it is nondiscriminatory, allows
      increased awareness of actual risk for infection, and provides an opportunity for
      earlier detection of HIV.

PMID- 15719873
TI  - Inadequate community knowledge about sickle cell disease among African-American
      women.
AB  - BACKGROUND: Federal legislation was passed in 1972 initiating genetic screening
      and community education about sickle cell disease (SCD). Few assessments have
      examined the impact of these programs. The aim of this study is to assess
      existing knowledge about SCD among African-American women in St. Louis, MO.
      METHODS: We conducted a cross-sectional telephone survey of African-American
      women, 18-30 years of age. Participants were recruited through random-digit
      dialing in six ZIP codes with greater than 75% African-American residents. The
      survey contained questions exploring four content domains about SCD: general
      knowledge, genetics, management and educational resources. RESULTS: A total of
      264 women were contacted; 30% were unable to complete the survey and participate
      further because they were unaware of SCD. One-hundred-sixty-two women met
      eligibility criteria, agreed to be surveyed and were included in the study.
      Ninety-one percent of the participants believed that SCD was a hereditary blood
      disorder, but only 9.3% understood the inheritance pattern. Eleven percent of the
      women were unaware of their sickle cell trait status. Most women recognized pain
      (94%), infections (80%) and strokes (40%) as complications of SCD. CONCLUSION:
      New strategies are needed to enhance awareness of SCD among African-American
      women of childbearing age.

PMID- 15719872
TI  - Factors associated with BMI, weight perceptions and trying to lose weight in
      African-American smokers.
AB  - This study examined sociodemographic, behavioral and psychosocial factors
      associated with BMI, weight perceptions and trying to lose weight among African
      American smokers (N=600, M=44.2 years, 70% female). Sixty-eight percent of the
      sample were overweight or obese (sample BMI M=28.0, SD=6.7). Three separate,
      simultaneous multivariable regression models were used to determine which factors
      were associated with BMI, weight perceptions and trying to lose weight. Poorer
      health, female gender and high-school education or higher were significantly
      associated with higher BMIs (p<0.05). Being female (OR=5.8, 95% CI=3.6-9.3) and
      having a higher BMI (OR=0.6, 95% CI=0.5-0.6) was associated with perception of
      overweight and smoking more cigarettes per day (OR=1.0, 95% CI=1.0-1.1), and
      perceiving oneself as overweight (OR=14.1, 95% CI=8.2-24.2) was associated with
      trying to lose weight. Participants somewhat underestimated their BMI in their
      weight perceptions. Those who perceived themselves as overweight were more likely
      to be trying to lose weight; therefore, increasing participant awareness of
      actual BMI status may lead to improved weight-control efforts in African-American
      smokers. Several expected associations with outcomes were not found, suggesting
      that BMI and weight constructs are not well-understood in this population.

PMID- 15719874
TI  - The associations of hormone replacement therapy and preventive practices in
      minority women.
AB  - OBJECTIVES: Minority women are less likely to use hormone replacement therapy
      (HRT), and the health characteristics associated with HRT use in this population
      are not well studied. We sought to examine the sociodemographic characteristics,
      health and preventive practices associated with HRT use among minority women.
      DESIGN: Survey SETTING: Inpatient and outpatient units of a teaching hospital.
      PARTICIPANTS: A convenience sample of 333 minority women aged 50 and above.
      VARIABLES: HRT use, demographic and lifestyle characteristics, and selected
      preventive practices. RESULTS: 14% of the study population, all minority women
      were using HRT. Regular exercise (p=0.03), and good perceived health status
      (p=0.02) were significant predictors of HRT use. None of the cancer screening
      measures studied were associated with HRT use. CONCLUSIONS: Only a small
      proportion of minority women were using HRT. Regular exercise and perceived good
      health were significant predictors of HRT use.

PMID- 15719875
TI  - Major limb amputations: an audit of indications in a suburban surgical practice.
AB  - BACKGROUND: Advancements in vascular and microsurgery in developed countries have
      led to fewer major limb amputations. AIM: This audit of major limb amputations
      performed at the Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria,
      between June 1998 and May 2003, was conducted to find out the indications for
      amputation and highlight those cases that could be salvageable. PATIENTS AND
      METHODS: This was a retrospective study. Case notes of all patients who had major
      limb amputations were examined for patients' age, sex, time of presentation, limb
      affected, indications for amputation, the severity of crush injury to limb, stage
      of musculoskeletal tumors and Wagner's grade of diabetic foot. RESULTS: A total
      of 71 limbs were amputated in 69 patients; 56 limbs (78.1%) were unsalvageable,
      while 15 limbs (21.1%) were salvageable. Trauma accounted for 76% followed by 22%
      performed due to gangrene secondary to diabetes mellitus. Out of the 56
      unsalvageable limbs, 31 patients presented with severely crushed limbs. Out of
      the 15 salvageable limbs, there were 11 cases of clean-cut traumatic amputations,
      two of soft-tissue sarcoma and one each of ruptured popliteal aneurysm and
      stenosed popliteal artery. CONCLUSION: Trauma and diabetes mellitus were leading
      indications for amputation. Expertise in limb salvage procedures and availability
      of appropriate equipment may reduce the numbers of amputations performed.

PMID- 15719876
TI  - The utility of lactate dehydrogenase isoenzyme pattern in the diagnostic
      evaluation of malignant and nonmalignant ascites.
AB  - OBJECTIVE: Lactate dehydrogenase (LDH), a tetrameric protein composed of four
      monomers, is expressed as five isoenzymes. Serum LDH isoenzymes may be useful in
      differential diagnosis of ascites etiology since tissue damage releases
      isoenzymes contained therein, leading to a change in their pattern. MATERIALS AND
      METHODS: We determined ascitic fluid LDH level and LDH isoenzyme activities in
      patients with malignant and nonmalignant ascites in a total of 76 patients (43
      males and 33 females). RESULTS: LDH level, LDH-4 activity and LDH-5 activity were
      found to be significantly higher, and LDH-1 activity was found to be lower in
      malignant ascites when compared with nonmalignant ascites. LDH-1 activity was
      detected to be significantly higher in the sterile cirrhotic ascites when
      compared with spontaneous bacterial peritonitis, malignant ascites, tuberculous
      ascites and congestive heart failure-related ascites. LDH-2 activity was found to
      be higher in spontaneous bacterial peritonitis when compared with the other
      groups. LDH-3 activity was detected to be higher in spontaneous bacterial
      peritonitis, malignant ascites and tuberculous ascites when compared with the
      sterile cirrhotic ascites. In the diagnosis of malignant ascites, the sensitivity
      and specificity were 96% and 76% for LDH level, 90% and 70% for LDH-1 activity,
      94% and 62% for LDH-4 activity, and 100% and 56% for LDH-5 activity,
      respectively. CONCLUSION: Ascitic LDH and its isoenzyme pattern may be helpful
      for the differential diagnosis of the most common causes of ascites: cirrhosis,
      spontaneous bacterial peritonitis, congestive heart failure, tuberculosis and
      malignancy.

PMID- 15719877
TI  - Medical volunteers: guidelines for success and safety.
AB  - Many African Americans from a variety of medical specialties are interested in
      satisfying a life-long dream of visiting Africa by volunteering their services to
      faith-based and private volunteer organizations doing missionary work on the
      continent. While this can be an extremely rewarding experience in which
      measurable good can be accomplished, this path can also be strewn with many
      obstacles that will affect both the success of the mission and the personal well
      being of the volunteer. The American Medical Team for Africa is a nonprofit, tax
      exempt, volunteer organization that has been doing medical missionary work in
      Africa since 1993. This manuscript is a compilation of this 10-year experience
      that has established some very useful guidelines for insuring a successful and
      safe mission if you are fortunate enough to have this opportunity.

PMID- 15719878
TI  - Elder abuse--"society's dilemma".
AB  - Elder abuse and neglect has been recognized as a growing problem in the United
      States, and this trend is likely to increase unless firm steps are taken to
      prevent it. All 50 states have reporting requirements for elder abuse and
      neglect. However, to date, there is no federal policy requiring reporting of
      elder abuse and neglect. In order to stem the tide of this awful scourge on
      society, we must continue to train caregivers and healthcare workers in the
      proper care and treatment of our elder citizens. Healthcare workers, especially
      emergency medicine physicians and nurses, must take the lead in this endeavor.
      There must be organized programs in healthcare facilities to facilitate the
      training of medical personnel. Scientific literature suggests that the abusers
      appear to be family members and caretakers of the elderly. Goals for prevention
      include enhancing quality of life, preventing family breakdown, and keeping the
      elderly persons in their homes as long as possible, if this is their wish.
      Intervention appears to be one of the best ways of prevention.

PMID- 15719879
TI  - Pleomorphic rhabdomyosarcoma of the diaphragm.
AB  - Pleomorphic rhabdomyosarcoma of the diaphragm represents fewer than 0.0001% of
      all cancers. One case is reported, and a total of eight cases to date are
      reviewed. It is an adult disease of both sexes, the lowest reported age being 14
      years. The tumor presents at a late stage, and the average symptom-death interval
      is only a few months. Early diagnosis and wide excision are essential along with
      radiotherapy and chemotherapy before any survival--much less worthwhile survival-
      can be hoped for. There is evidence of host immune response against
      rhabdomyosarcomas. Immunotherapy, therefore, should be considered. For assessment
      of the biological behavior of the tumor and the treatment, standardization of
      staging and grading are essential, although there is some evidence that the
      prognosis of primary and recurrent tumors treated radically are similar.

PMID- 15719880
TI  - Three successive generations of women with anhidrotic/hypohidrotic ectodermal
      dysplasia.
AB  - We describe the findings of anhidrotic/hypohidrotic ectodermal dysplasia in three
      successive generations of a family. All three women had variable alopecia,
      anhidrosis, hypodontia and malar hypoplasia. Chromosomal studies revealed a
      defect of the 2q12 region in all three patients. Previous studies have reported
      rare cases of autosomal dominant ectodermal dysplasia associated with defects in
      the 2q11-13 region1. These rare disorders are characterized by common anomalies
      of at least two elements of the ectoderm and its appendages--namely, the skin,
      teeth, hair, nails and sweat glands. These patients also frequently have chronic
      dental problems with early loss of teeth and recurrent lung, ear and nose
      infections secondary to a defect in mucous membrane function. The majority of
      reported cases of ectodermal dysplasias have historically been X-linked
      recessive, but our findings indicate that an autosomal version may be more
      prevalent than previously thought.

PMID- 15719881
TI  - Alexander Thomas Augusta--physician, teacher and human rights activist.
AB  - Commissioned surgeon of colored volunteers, April 4, 1863, with the rank of
      Major. Commissioned regimental surgeon on the 7th Regiment of U.S. Colored
      Troops, October 2, 1863. Brevet Lieutenant Colonel of Volunteers, March 13, 1865,
      for faithful and meritorious services--mustered out October 13, 1866. So reads
      the tombstone at Arlington National Cemetery of Alexander Thomas Augusta, the
      first black surgeon commissioned in the Union Army during the Civil War and the
      first black officer-rank soldier to be buried at Arlington Cemetery. He was also
      instrumental in founding the institutions that later became the hospital and
      medical college of Howard University and the National Medical Association.

PMID- 15719882
TI  - Understanding patient health beliefs, enhancing long-term professional
      satisfaction.

PMID- 15719884
TI  - Multilingual approach to "Web of Science".

PMID- 15719885
TI  - Urban healthcare under attack.

PMID- 15719887
TI  - Hypochromic reticulocytes, hypochromic erythrocytes and p-transferrin receptors
      in diagnosing iron-deficient erythropoiesis.
AB  - BACKGROUND: The purpose of this study was to test the hypothesis that hypochromic
      reticulocytes, hypochromic erythrocytes and p-transferrin receptors are sensitive
      variables in detecting iron-deficient erythropoiesis in healthy subjects and
      hemodialysis patients. METHODS: Study 1: Twenty-one blood donors donated 450 mL
      blood. During the following 2 weeks blood samples were analyzed for the variables
      mentioned above. Study 2: Twenty-eight blood donors received 10,000 U recombinant
      human erythropoietin (rHuEPO) twice in the first week or placebo, after they had
      donated 450 mL blood. During the following 3 weeks the blood samples were
      analyzed for the variables mentioned in Study 1. Study 3: Eighteen hemodialysis
      patients receiving rHuEPO and iron treatment had either iron treatment
      discontinued for 4 weeks, after which iron was resumed, or received unchanged
      treatment. During 8 weeks blood samples were analyzed for the variables mentioned
      in Study 1. RESULTS: Study 1: Blood donation induced an increase in hypochromic
      reticulocytes of 178%, in hypochromic erythrocytes the increase was 267%, and in
      p-transferrin receptors 32%. Study 2: Treatment with rHuEPO induced a more
      pronounced increase than placebo in hypochromic reticulocytes (232% vs. 158%) and
      hypochromic erythrocytes (1240% vs. 300%), but not in p-transferrin receptors.
      Study 3: Discontinuation of iron treatment did not cause any significant
      differences in the variables mentioned above between the two groups, but caused a
      25% decrease in p-ferritin. When iron treatment was resumed, p-ferritin increased
      by 19%. We found no significant changes in the control group. CONCLUSIONS:
      Hypochromic reticulocytes, hypochromic erythrocytes and p-transferrin receptors
      are sensitive variables in the early detection of iron-deficient erythropoiesis
      in healthy subjects, but in this study the iron withdrawal period was too short
      to show the value of these variables in the detection of iron-deficient
      erythropoiesis in hemodialysis patients.

PMID- 15719888
TI  - Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and
      apolipoprotein B: relationships among the different measurements.
AB  - Serum low-density lipoprotein cholesterol (LDLC) value is a recognized target for
      atherosclerotic risk management, and is generally calculated using the
      "Friedewald formula". Alternative risk markers include directly measured LDLC,
      non-high-density lipoprotein cholesterol (non-HDLC) and apolipoprotein B (ApoB).
      The relationships among such various measured or calculated quantities in medium
      sized sets of patient results were investigated. Results from two sets of
      patients were retrieved from our laboratory information systems. One group
      (n=8436) included results of cholesterol, HDLC, triglyceride (TG) and glucose
      measurements. A second group (n = 902) included, in addition, results of ApoB
      measurement. The results confirmed the unreliability of the Friedewald formula at
      TG >350 mg/dL (3.96 mmol/L), but also indicated TG-linked underestimation of LDLC
      below such a TG level. By contrast, non-HDLC values were shown to be independent
      of TG, and better correlated to ApoB than LDLC values. Mathematically, the
      difference between non-HDLC and LDLC is TG x 0.458 (values in mmol/L): therefore,
      the latter cannot be compared to (or converted into) the former by simply adding
      a constant amount. The ratio LDLC/ApoB was shown continuously to decrease with
      increasing TG concentrations, while the ratio non-HDLC/ApoB did not. The TG
      dependent underestimation of LDLC may be the reason for the reported better
      cardiovascular risk predictivity of non-HDLC in diseases associated with TG
      increase, such as in diabetes. Non-HDLC values are not influenced by TG levels,
      and are better correlated with ApoB.

PMID- 15719889
TI  - Distribution and determinants of serum creatinine in the general population: the
      Hordaland Health Study.
AB  - BACKGROUND: Serum creatinine is a well-recognized risk factor for cardiovascular
      disease (CVD) and is also a rough measure of glomerular filtration rate. The
      purpose of the present study was to investigate determinants of serum creatinine
      in the general population. METHODS: The participants were recruited as a part of
      the Hordaland Health Study, and included 6952 men aged 41-49 years, 8218 women
      aged 41-49 years, 1470 men aged 71-74 years and 1865 women aged 71-74 years. Data
      on lifestyle factors, medical history and medication were obtained through
      questionnaires. Body size and blood pressure measurements as well as non-fasting
      blood samples were obtained during a health examination. Determinants of serum
      creatinine were identified using multiple linear and logistic regression
      analyses. RESULTS: Male and older participants had higher levels of serum
      creatinine than female and middle-aged participants. For older participants,
      creatinine was associated with serum triglycerides, CVD, upper-arm circumference
      and use of antihypertensive drugs as well as inversely associated with cigarette
      smoking. For middle-aged participants, creatinine was associated with upper-arm
      circumference, serum lipids and physical exercise, as well as inversely
      associated with smoking and alcohol intake. The associations with CVD risk
      factors were much stronger for older participants than for middle-aged
      participants and most associations were significant after adjustments as well as
      present within the reference range of serum creatinine. CONCLUSIONS: In this
      general population sample, high serum creatinine levels were associated with risk
      factors for CVD. These associations were stronger in older subjects, whereas in
      middle-aged subjects lifestyle variables were relatively more important.

PMID- 15719890
TI  - Real-time polymerase chain reaction is a sensitive and precise method for
      quantifying transcription from reporter plasmids.
AB  - Sensitive methods are required for studying promoter activity of weakly expressed
      genes using reporter systems. In this study it is shown that the sensitivity of
      the traditional enzymatic assay for measuring LacZ activity is too low when
      studying the promoter activity of epiregulin, a member of the epidermal growth
      factor (EGF) system. Consequently, a new real-time polymerase chain reaction
      (PCR) method was developed to evaluate the expression of the reporter gene LacZ.
      This method can be used for monitoring promoter activity of weakly expressed
      genes. T24A cells with LacZ expression driven by the cytomegalovirus (CMV)
      promoter were used to compare real-time PCR and the traditional enzymatic
      detection system. The real-time PCR method had a more than 1000-fold higher
      sensitivity than the enzymatic assay. LacZ mRNA could be quantified from as few
      as two cells with an imprecision of 19%. The increased sensitivity enabled the
      measurement of LacZ mRNA transcription driven by the epiregulin promoter in
      stably transfected T24A bladder cancer cells. This allowed a reproducible
      quantification of a 3-fold transcriptional increase from the epiregulin promoter
      caused by serum stimulation of stably transfected T24A cells. Clearly, this new
      method is well suited to quantify relatively small changes in transcriptional
      activity from weakly expressed genes.

PMID- 15719891
TI  - Urine analysis and decision-making on cystitis in general practice.
AB  - Decision-making on cystitis in general practice was studied by addressing 1171
      general practitioners of whom 909 responded. A case history was supplied with a
      test-strip result where leucocyte esterase was 1 + and the nitrite field either
      positive or negative. The respondents' estimated probability of urinary tract
      infection from the history had a median at 50% (10 and 90 percentiles, 30% and
      90%). The test-strip results changed the estimate to 90% (50% and 100%) in the
      nitrite-positive group and 50% (10% and 90%) in the nitrite-negative group.
      Likelihood ratio was calculated from each respondent's estimated pre- and post
      test probability to express the test's assumed diagnostic power. The median
      likelihood ratios were 4.75 (10 and 90 percentiles, 1.00 and 35.70) in the
      nitrite-positive group and 1.00 (0.11 and 4.00) in the nitrite-negative group.
      The resulting actions taken by the respondents were: no action (14 respondents,
      corresponding median estimated post-test probability 27.5%), await further
      examination (482, 50%) and prescription of antibiotics (366, 90%). Further
      examination included urine microscopy (13%), bacteriologic culture (21%), or both
      (65%). Eight-two percent of respondents who decided to prescribe antibiotics
      would also perform further examinations. In routine urine analysis, 79% of
      respondents request only test strips, 2% perform microscopy and 19% do both. The
      estimated probability of urinary tract infection is significantly affected by
      test-strip results and is important for the choice of further actions. Microscopy
      is performed more often than recommended in other studies.

PMID- 15719892
TI  - Prevention of catheter thrombosis increases survival, but does not modify lung
      injury in rats receiving long-term parenteral nutrition.
AB  - It has previously been shown that rats receiving total parenteral nutrition (TPN)
      or each component of TPN die within 40 days of treatment. Central catheter
      thrombosis and lung injury were constant findings. The aim of the present study
      was to examine the impact of central thrombosis on lung injury and survival in
      rats receiving long-term parenteral nutrition. In the first part of the study TPN
      was infused via the jugular vein and incidence of central venous thrombosis and
      rate of survival were recorded. Addition of low molecular weight heparin (LMWH)
      reduced central thrombosis from 6 out of 7 animals to 2 out of 7 animals
      (p=0.027) and increased survival from 17.1+/-4.5 days to 32.4+/-4.9 days
      (p=0.04). In the second part of the study four infusion groups were established.
      Group 1 (controls) received saline 100 mL/kg/day via the jugular vein (n=6).
      Group 2 received Intralipid 40 mL/kg/day via the jugular vein (n = 7). Group 3
      received Intralipid 40 mL/kg/day via the portal vein (n = 7). Group 4 received
      Intralipid 40 mL/kg/day with added LMWH 70 U/kg/day (n = 7). Lung injury and
      occurrence of central thrombosis were investigated. Lung injury was assessed by
      measuring pulmonary arterial pressure (Ppa), clearance of serotonin by the
      vascular endothelium and the capillary filtration coefficient (CFC). Either
      infusion via the portal vein or the addition of LMWH to the infusion via the
      jugular vein prevented central thrombus formation, but the lung injury was not
      modified by this method compared with infusing Intralipid via the jugular vein
      without LMWH. In conclusion, central thrombus formation contributes to death in
      rats receiving parenteral nutrition. The mechanism of the injurious effect of
      central thrombosis remains unknown, but central thrombus formation seems not to
      increase lung injury caused by Intralipid.

PMID- 15719893
TI  - Does an enzyme other than thrombin contribute to unexpected changes in the levels
      of the different forms of thrombin activatable fibrinolysis inhibitor in patients
      with hemophilia A, hemophilia B and von Willebrand disease?
AB  - Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI), also called plasma
      procarboxypeptidase B or U, is one of the modulators of fibrinolysis in blood.
      Pro-TAFI is activated by thrombin/thrombomodulin complex or by plasmin to a
      carboxypeptidase B-like enzyme (TAFI) of 35.8 kD molecular weight. TAFI
      spontaneously becomes inactive as a result of a temperature-dependent
      conformational change in the protein (TAFIi). In this study, pro-TAFI, total TAFI
      antigen and TAFI-TAFIi antigen levels were measured in 32 patients with
      hemophilia A, 4 patients with hemophilia B, 21 patients with von Willebrand
      disease (VWD) and 13 healthy controls. A statistically significant decrease in
      pro-TAFI was found in all groups (10.72+/-4.57 mg/L (p<0.001); 8.00+/-2.35 mg/L
      (p<0.01) and 8.98+/-2.33 mg/L (p <0.001) for hemophilia A, hemophilia B and VWD,
      respectively) compared to controls (17.85+4.61 mg/L). A statistically significant
      increase in TAFI-TAFIi antigen was found in hemophilia A (1.05+/-1.01 mg/L)
      (p<0.05) and in VWD patients (0.96+/-1.01 mg/L) (p<0.05) compared to controls
      (0.55+/-0.36 mg/L). There was no difference in total TAFI antigen levels between
      any group of patients and the controls. Neither did pro-TAFI nor TAFI-TAFIi
      levels differ within the group of hemophilia A patients in relation to severity
      (mild, moderate and severe) or among the VWD patients in relation to subtype
      (type 1, type 2A and type 3). These findings indicate an increased conversion of
      pro-TAFI to TAFI and/or TAFIi in patients with bleeding disorders. As thrombin
      generation is seriously impaired in these patients and almost absent in
      hemophilia A and B and in type 3 VWD, it is possible that plasmin mediates pro
      TAFI activation in these patients. Enhanced fibrinolysis via generation of
      plasmin has previously been reported in hemophilia and VWD. Activation of pro
      TAFI by plasmin may be a feedback mechanism that counterbalances increased
      fibrinolysis in patients with bleeding disorders. The relationship between the
      TAFI activation pathway and bleeding complications associated with hemophilia A,
      hemophilia B and VWD requires further investigation.

PMID- 15719894
TI  - Methodological aspects of measuring oxidized low density lipoproteins in human
      serum and plasma.

PMID- 15719895
TI  - A guide to child nonverbal IQ measures.
AB  - This guide provides a basic overview of 16 child nonverbal IQ measures and uses a
      set of specified criteria to evaluate them in terms of their psychometric
      properties. In doing so, the goal is neither to validate nor to criticize current
      uses of IQ but to (a) familiarize clinicians and investigators with the variety
      of nonverbal IQ measures currently available, (b) highlight some of the important
      distinctions among them, and (c) provide recommendations for the selection and
      interpretation of nonverbal IQ measures.

PMID- 15719896
TI  - Relations among maternal, child, and demographic factors and the persistence of
      preschool language impairment.
AB  - This research used the National Institute of Child Health and Human Development
      Study of Early Child Care database of 1,364 children to identify children at 3
      years of age who could generally be characterized as exhibiting specific language
      impairment. Seventy-three identified children were classified into 2 groups on
      the basis of standardized assessment of language skills at 4.5 years: children
      whose language impairment had resolved (n = 33) versus those whose language
      impairment persisted (n = 40). A logistic regression model using measures of
      maternal sensitivity, maternal depression, child externalizing behaviors, child
      health history, family income-to-needs ratio, and quality of home environment was
      used to predict group membership. Maternal sensitivity and maternal depression
      contributed significantly to the prediction model for group membership. Results
      are discussed in terms of theoretical and clinical implications.

PMID- 15719897
TI  - Narrative skills in children with selective mutism: an exploratory study.
AB  - Selective mutism (SM) is a rare and complex disorder associated with anxiety
      symptoms and speech-language deficits; however, the nature of these language
      deficits has not been studied systematically. A novel cross-disciplinary
      assessment protocol was used to assess anxiety and nonverbal cognitive, receptive
      language, and expressive narrative abilities in 7 children with SM and a
      comparison group of 7 children with social phobia (SP). The children with SM
      produced significantly shorter narratives than children with SP, despite showing
      normal nonverbal cognitive and receptive language abilities. The findings suggest
      that SM may involve subtle expressive language deficits that may influence
      academic performance and raise additional questions for further research. The
      assessment procedure developed for this study may be potentially useful for
      language clinicians.

PMID- 15719898
TI  - The single exposure: partial word knowledge growth through reading.
AB  - A critical aspect of the assessment of children's word learning processes is the
      examination of word knowledge growth over time. The purpose of this study was to
      examine the types of partial word knowledge (PWK) growth that occurred from 1
      exposure to unfamiliar words in text, taking into account the roles of part of
      speech and individual language skills. Sixth-grade children with normal language
      read stories containing unfamiliar nouns and verbs. The children then completed 2
      tasks to assess PWK. Results were that at least 1 type of PWK developed:
      knowledge that a word exists as a lexical entry in the language. Part of speech
      appeared to play a role; significant PWK at posttest was apparent for verbs but
      not for nouns. Children's language skills did not appear to impact the amount of
      PWK demonstrated at posttest.

PMID- 15719899
TI  - A language screening protocol for use with young African American children in
      urban settings.
AB  - Language screenings represent an important tool for early identification of
      language impairments in young children between 3 and 5 years of age. This
      investigation examined the utility of a well-established set of assessment
      measures for screening young African American children. One hundred and ninety
      six children participated in the screening. Based upon the outcomes of the
      screening, 25 children who failed and a random sample of 56 children who passed
      were administered a larger language and cognitive assessment battery. Sensitivity
      and specificity of the screening were determined to be high. The number of
      different words, the Kaufman Nonverbal Scale, and nonword repetition accounted
      for a significant amount of the variance in performance. The screening is brief,
      valid, and culturally fair for use with preschool- and kindergarten-aged African
      American children living in urban settings.

PMID- 15719900
TI  - The influence of multiple presentations on judgments of children's phonetic
      accuracy.
AB  - Two experiments examined whether listening to multiple presentations of recorded
      speech stimuli influences the reliability and accuracy of judgments of children's
      speech production accuracy. In Experiment 1, 10 listeners phonetically
      transcribed words produced by children with phonological impairments after a
      single presentation and after the word was played 7 times. Inter- and
      intratranscriber reliability in the single- and multiple-presentation conditions
      did not differ significantly. In Experiment 2, 18 listeners provided binary
      correct/incorrect judgments of /s/ accuracy in single- and multiple-presentation
      conditions. There was no systematic effect of presentation condition on either
      accuracy or intrarater reliability. However, greater interrater reliability was
      noted in the multiple-presentation condition, particularly for tokens of /s/ that
      were incorrect or acoustically intermediate between an incorrect and a correct
      /s/. Taken together, the results suggest that multiple presentations have no
      measurable effect on the accuracy and intrarater reliability of judgments of
      children's phonetic accuracy, but that they do have a small effect on interrater
      reliability. Clinical implications are discussed.

PMID- 15719902
TI  - An evaluation of preoperative skin antiseptics.
AB  - An underpinning tenet of evidence-based practice is that all routine practices
      should be open to scrutiny. Questioning practice should not be limited to new,
      experimental procedures, but should also include examination of 'tried and
      trusted' techniques. Taking this perspective, the author recently contributed to
      a systematic review evaluating the use of antiseptics preoperatively.

PMID- 15719903
TI  - Support workers and the scrub role.

PMID- 15719904
TI  - Latex sensitivity awareness in preoperative assessment.
AB  - The role of the preoperative assessment practitioner (POAP) has evolved hugely to
      allow them to become more autonomous in decision-making, particularly in the
      design of local protocols and guidelines for preoperative assessment. Good
      practice guidelines are imperative to ensure that all requirements for the
      patient have been identified before the day of surgery, which minimises the risk
      of late cancellations.

PMID- 15719905
TI  - Patient autonomy. Legal and ethical issues in the post-anaesthetic care unit.
AB  - The need for patient autonomy, empowerment and choice has become central to
      health reforms. Confronted with the prospects of such perpetual changes, respect
      for patient autonomy has to be tempered with paternalistic beneficence. This
      article discusses the difficulties encountered when applying patient autonomy
      within the post-anaesthetic care unit (PACU), evaluating ethical, legal and
      professional issues.

PMID- 15719906
TI  - Environmental perspectives.

PMID- 15719907
TI  - Agricultural applications of dielectric spectroscopy.
AB  - A brief account of interest in dielectric properties of agricultural materials is
      presented, and some examples of dielectric spectroscopy applied to agricultural
      problems are discussed. Included are wide frequency range (250 Hz to 12 GHz)
      permittivity, or dielectric properties, measurements on adult rice weevils and
      hard red winter wheat, for the purpose of assessing selective dielectric heating
      of the insects, and broadband (200 MHz to 20 GHz) permittivity measurements on
      tissues of fresh fruits and vegetables. Similar measurements are shown for tree
      ripened peaches, which were obtained to assess possibilities for a permittivity
      based maturity index. Broadband (10 MHz to 1.8 GHz) permittivity measurements are
      shown for several fruits and vegetables as a function of temperature from 5 to 95
      degrees C. Measurements over the same frequency range and similar temperature
      ranges are presented for two other food products, whey protein gel and apple
      juice. A few comments are offered on likely future dielectric spectroscopy
      applications in agriculture.

PMID- 15719908
TI  - 3-dimensional numerical modeling of an industrial radio frequency heating system
      using finite elements.
AB  - This paper presents a new, yet simple and effective approach to modeling
      industrial Radio Frequency heating systems, using the wave equation applied in
      three dimensions instead of the conventional electrostatics method. The central
      idea is that the tank oscillatory circuit is excited using an external source.
      This then excites the applicator circuit which is then used to heat or dry the
      processed load. Good agreement was obtained between the experimental and
      numerical data, namely the S11-parameter, phase, and heating patterns for
      different sized loads and positions.

PMID- 15719909
TI  - Principles for microwave moisture and density measurement in grain and seed.
AB  - The importance of cereal grain moisture content in determining time of harvest
      and in preserving grain quality is described. Techniques for moisture
      measurement, including electronic moisture meters, are also discussed briefly,
      and the need for better moisture sensing techniques for modern agricultural on
      line moisture monitoring is described. Principles of microwave free-space
      measurements involving attenuation and phase-shift determination are explained,
      and density-independent functions of the grain permittivity are presented that
      permit reliable moisture sensing applicable to moving grain in which bulk density
      variation occurs. Three different approaches are discussed for determining
      moisture content and bulk density of grain from microwave measurement of the
      dielectric properties. A new moisture calibration function, based on complex
      plane plots of dielectric constant and loss factor, each divided by bulk density,
      is described, which promises a universal calibration for different types of grain
      and seed. This important advantage should encourage commercial development for
      practical use.

PMID- 15719910
TI  - Refining occlusion with muscle balance to enhance long-term orthodontic
      stability.
AB  - The primary objective of orthodontic treatment is the movement of teeth into a
      more ideal relationship, not only for aesthetic, but also for functional
      considerations. Another very important objective, often not given enough
      consideration, is the need to finish the case with the muscles of mastication in
      equilibrium. If muscle balance is not achieved, an endless procession of
      retainers is required for retention. In simple terms, if the occlusal forces in
      maximum intercuspation are unevenly distributed around the arch, tooth movement
      will most likely occur. Today, however, it is possible to simultaneously and
      precisely measure the relative force of each occlusal contact, the timing of the
      occlusal contacts and the specific muscle contraction levels. This technological
      breakthrough represents a paradigm shift in thinking and may improve orthodontic
      stability.

PMID- 15719911
TI  - Use of orthopedic finger distractor for facial asymmetry correction.
AB  - Facial asymmetry after unilateral ankylosis results due to the loss of the
      condylar growth center on the ankylosed side. This results in the skeletal
      midline deviating to the affected side, a lack of vertical growth on the same
      side produces a cant of the occlusal plane and mandibular retrognathism is seen
      as a result of the hypoplasia. The lower border of the mandibular corpus and
      angle on the contra lateral side is usually flattened. We report a case of facial
      asymmetry following unilateral ankylosis, which was treated by a combined
      approach with distraction osteogenesis and orthodontics. Inexpensive orthopedic
      finger distractors were used. The facial changes were analyzed using the Grummons
      facial asymmetry analysis.

PMID- 15719912
TI  - Managing morphologically atypical impacted teeth orthodontically.
AB  - Impactions with severely dilacerated root is seldom reported, especially the
      maxillary incisor. It is probably because of the high clinical difficulty of
      bringing the dilacerated tooth into position: most patients probably would choose
      extraction with replacement by prosthesis instead. However, the philosophy seems
      to have changed recently. We report two cases one in which an impacted central
      incisor was brought in the arch by orthodontic traction. In the second case the
      impacted premolar was brought into the arch and was shaped as a mandibular canine
      for achieving a good functional occlusion.

PMID- 15719913
TI  - Treatment strategy for patients with ectodermal dysplasia: a case report.
AB  - Ectodermal dysplasia (ED) is a hereditary condition characterized by abnormal
      development of the skin, hair, nails, sweat glands, and the stomatognathic
      system. There are many different types of ectodermal dysplasia of which X-linked
      anhidrotic ectodermal dysplasia is the most common. Multiple genes have been
      discovered to cause ectodermal dysplasias. With any form of ED, children may
      display a range of symptoms and challenging rehabilitation. This clinical report
      presents the treatment plan for a young patient with ED and anodontia requiring
      prosthetic restoration.

PMID- 15719914
TI  - Oral defensiveness: children with a dysfunction of sensory regulation.
AB  - Oral defensiveness is a relatively newly discussed cluster of behavioral symptoms
      with a theorized physiological basis, which may manifest itself during a child's
      dental visit. Dentists aware of oral defensiveness and its distinct
      manifestations will be able to discuss with their patient's parents regarding
      this condition and if necessary modify their approach when treating children
      diagnosed with oral defensiveness. The purposes of this paper are to acquaint
      dentists with this controversial disorder, to increase awareness of its
      occurrence, and to suggest possible interventions for alleviating aversive
      responses to typical dental experiences when no other cause is apparent. A review
      of pertinent literature is presented. A list of characteristics and a list of
      other types of sensory defensiveness are also presented.

PMID- 15719915
TI  - A vacuum-formed splint for luxated tooth with a repositioning on the model.
AB  - The results of fixation of a luxated tooth using a vacuum-formed splint, formed
      on a plaster model after repositioning of the luxated tooth on the model are
      presented. This may be useful where the adjacent tooth gap is wide or only
      minimal anchorage and support are available from the adjacent teeth.

PMID- 15719916
TI  - Tooth loss and subluxation in the primary dentition: a twelve-year follow-up case
      report.
AB  - The case of a five-year-old child is reported, who suffered dento-alveolar injury
      including subluxation of the right upper lateral incisor and avulsion of the
      upper central incisors and left upper lateral incisor and laceration in the
      mucosa. The case was followed for 12 years until complete root formation and
      alignment of the anterior permanent teeth.

PMID- 15719917
TI  - Clinical evaluation of three different materials used as pit and fissure sealant:
      24-months results.
AB  - To evaluate the retention and caries experience effects of three different
      materials used as fissure sealants after 24 months of clinical application: a
      resin-modified glass ionomer cement (A), a flowable resin composite (B) and a
      compomer (C). One hundred and seventeen (117) teeth were sealed with material A,
      119 teeth with material B and 120 teeth with material C. Children were randomly
      assigned. Each one received only one of the materials studied. Plaque index, dmft
      score and socioeconomic level were scored at baseline. The clinical exams were
      conducted 6, 12 and 24 months after application of the sealant. Statistical
      analysis (Kruskal-Wallis) revealed that there were statistically significant
      differences between the retention rates of groups A and B and between groups B
      and C after 2 years, with material B showing better results. After 2 years, 3.1%
      of the teeth of group A, 4.3% of group B and 6.7% of group C were Carious+Filled.
      There was no evidence of association between caries presence after 2 years and
      plaque index, dmft score and socioeconomic level. These results suggest that
      flowable resin composite had a satisfactory retention after this period of
      evaluation and all three materials were effective on occlusal caries prevention.

PMID- 15719918
TI  - Alveolar bone loss in the primary dentition: state of the art.
AB  - Alveolar bone loss has been reported in primary teeth of healthy young children
      with a variable prevalence. This study aimed to review the literature on alveolar
      bone loss in the primary teeth of children without systemic diseases and to
      discuss the controversies with regard to the prevalence of this pathology in the
      primary dentition.

PMID- 15719919
TI  - Effects of plaque disclosing agents on esthetic restorative materials used in
      pediatric dentistry.
AB  - The aim of study was to evaluate the color stability of tooth-colored restorative
      materials usually used in pediatric dentistry after the application of two plaque
      disclosing agents. Twenty specimens of each material: a resin-modified glass
      ionomer, a composite resin and an ion-releasing composite resin, were prepared.
      Baseline color evaluation was performed, samples were exposed to the plaque
      disclosing agents: a basic fuchsin solution and a fluorescent dye, and new color
      evaluations were made. The resin-modified glass ionomer stained with basic
      fuchsin presented the greatest color change in the present study, and the
      fluorescent dye did not show statistically significant changes among the
      restorative materials. In conclusion, basic fuchsin dyes should be carefully used
      in children with a great number of tooth-colored restorations.

PMID- 15719920
TI  - Enamel opacities removal using two different acids: an in vivo comparison.
AB  - Computerized analysis assessed quantitatively the efficacy of microabrasion using
      37% phosphoric and 18% hydrochloric acids with pumice on removal of enamel
      opacities. Baseline and after one month photos were taken and analyzed by Paint
      Shop Pro 7 software and Image Pro Express 4.0. Nonparametric tests were used.
      Results depicted significant differences immediately versus one month post
      treatment for both acids. It was concluded that both acids can be used, and as
      time passes enamel color improvement occurs.

PMID- 15719921
TI  - Polyethylene ribbon fibers: a new alternative for restoring badly destroyed
      primary incisors.
AB  - Dentistry has advanced to the point where it is undesirable for children to be
      partially edentulous or to have unattractive anterior teeth. With the
      introduction of new materials and adhesive systems the use of polyethylene fibers
      as post and core offer a new reconstructive alternative for severely destroyed
      primary anterior teeth. These fibers offer root and coronal retention, stability
      and esthetics, and it is done chair side. The present study compared two
      different types of fibers and analyzed the fracture resistance between the two of
      them. Two groups were formed. Group I used non pre-impregnated resin fibers
      (glasSpan) and group II used pre-impregnated resin fibers (Splint-it). Both types
      of fibers have been used as post and core in the restoration of primary teeth and
      clinical studies have been published. Our results indicated that the mean
      fracture resistance for group I was 71.346 and for group II 97.952 (p = 0.004).
      During the observation of the fractured samples, adhesive failures were noted for
      group I at the junction between the fiber and its core to the interior wall of
      the root canal. In group II, the fibers were dislodged out of the canal and the
      core part of the canal remained intact. It can be concluded that pre-impregnated
      fibers offer a better fracture resistance when used as post in endodontically
      treated primary anterior teeth.

PMID- 15719922
TI  - Maxillary incisor palatal erosion: no correlation with dietary variables?
AB  - The objectives of the study were to examine a relationship between tooth erosion
      affecting the palatal aspects of permanent maxillary central incisors with
      dietary, behavioral and medical variables. The methods included, 251
      schoolchildren aged 11 to 13 years were recruited to participate. Each subject
      had dental impressions of the palatal aspects of both upper central incisors
      recorded at baseline, 9 and 18 months intervals. From these, electroconductive
      replicas were fabricated, mapped and compared using a surface matching technique.
      At the end of the study all participants underwent a structured interview that
      sought to assay the level of potential erosive dietary, behavioral and medical
      risk factors. Correlation analyses of the responses given in the final structured
      interview with the degrees of palatal tooth substance loss (both previous and
      measured) were under taken. The results showed: (1) The degree of previous
      erosion did not predict the level of measured ongoing erosion. (2) Brushing the
      teeth more frequently with fluoridated toothpaste correlated significantly with
      lower levels of ongoing erosion (P = 0 011). It was concluded that: (1) Evidence
      of previous palatal erosion did not predict future erosion. (2) The application
      of topical fluoride as a by-product of tooth brushing may provide an element of
      protection against palatal erosion. (3) In view of the lack of correlation
      between exposure to potential risk factors and the level of ongoing palatal tooth
      surface loss in this study, other factors (such as an individual's susceptibility
      and salivary buffering power) may well be more important predictors. The clinical
      relevance included: Preventive advice to patients with dental erosion should not
      only include the use of topical fluoride, in the form of toothpaste, but
      recognize individual susceptibility to this condition.

PMID- 15719923
TI  - Panoramic radiographs: determination of mandibular steepness.
AB  - The aim of this study was to evaluate the potential of panoramic radiographs to
      measure mandibular inclination and steepness. Standardized panoramic and lateral
      cephalometric radiographs were taken for 95 subjects (46 females, mean age 12.4
      +/- 1.2 years; 49 males, mean age 12.1 +/- 1.3 years). Mandibular inclination
      from panoramic radiograph was measured using gonial angle formed by the tangents
      of the lower border of the mandible and the distal border of the ascending ramus
      and the condyle. A correlation test was performed to check for similarity between
      the measurements. The mean values for the gonial angle were 127.3 +/- 6.2 and
      125.7 +/- 6.5 degrees measured from the panoramic and cephalometric radiographs
      respectively. A high correlation between the measurements taken from both
      radiographs was found (r = 0.83, P < 0.001). Panoramic radiographs are a useful
      tool for the measurement of gonial angle, which is an indicator of manibular
      steepness and subsequently mandibular growth direction. The ability to determine
      growth direction from the orthopantomogram will be useful because majority of
      dentists request an OPG for patients during routine dental examination. This will
      enable the dental professional to spot vertical growth problems using a readily
      available tool.

PMID- 15719924
TI  - Dental abnormalities of a long-term survivor of a childhood hematological
      malignancy: literature review and report of a case.
AB  - The treatment of haematological malignancy is multimodal and involves
      chemotherapy, radiotherapy and/or bone marrow transplants. With the advancement
      in cancer therapy, there is an increase in the survival of many children with
      childhood haematological malignancy. In addition, the late effect of the oncology
      treatment to the orofacial and dental development becomes significant in terms of
      the potential clinical impact that may affect the quality of life of the
      survivor. The severity of the long-term effects is dependent on the age of the
      child at initiation of treatment and whether chemotherapy is combined with
      radiation or not. The dental treatment may become more complex if the patient
      requires advanced restorative dental care and the roots malformation may
      complicate orthodontic treatment. Therefore these patients may require a
      scheduled careful preventive programme, long-term follow up, with prophylactic
      treatment and intervention at appropriate time to minimize the consequences of
      the disease and the given therapy.

PMID- 15719925
TI  - Oral soft tissue lesions in Greek children and adolescents: a retrospective
      analysis over a 32-year period.
AB  - Pediatric oral pathology encompasses a wide clinical spectrum of local and
      systemic diseases. The purpose of this study was to evaluate the clinical
      characteristics of oral soft tissue lesions in Greek children and adolescents up
      to 18 years old. Data available through a 32 year old period revealed that among
      the 1040 cases analyzed, benign lesions, mainly cysts, inflammatory lesions and
      reactive hyperplasias, were the most common causes for seeking dental advice
      during childhood.

PMID- 15719927
TI  - Bilateral protrusion of the buccal fat pad into the mouth of an infant: report of
      a case.
AB  - The buccal fat pad is an anatomic structure, which contributes significantly to
      the prominence of the newborn's and infant's cheek. It is probably important in
      the suckling mechanism. In this article a case of unusual protrusion of this
      structure into the oral cavity of an infant is described. Besides the two-years
      of follow-up, a review of the literature is presented and a differential
      diagnosis is outlined.

PMID- 15719926
TI  - Fetal intermediate rhabdomyoma of the lip: case report.
AB  - Fetal rhabdomyoma is a rare benign neoplasm of skeletal muscle that must be
      distinguished histologically from various malignant lesions, including
      rhabdomyosarcoma. They have recently been subdivided into two histological
      variants myxoid and cellular fetal rhabdomyomas. This article describes a case of
      an 8 month infant with a fetal rhabdomyoma in the upper lip. Illustrate the
      histological features and discusses the means of distinguishing these lesions
      from various other conditions with which they may be confused.

PMID- 15719928
TI  - Recognition of merged characters based on forepart prediction, necessity
      sufficiency matching, and character-adaptive masking.
AB  - Merged characters are the major cause of recognition errors. We classify the
      merging relationship between two involved characters into three types: "linear,"
      "nonlinear," and "overlapped." Most segmentation methods handle the first type
      well, however, their capabilities of handling the other two types are limited.
      The weakness of handling the nonlinear and overlapped types results from
      character segmentation by linear, usually vertical, cuts assumed in these
      methods. This paper proposes a novel merged character segmentation and
      recognition method based on forepart prediction, necessity-sufficiency matching
      and character-adaptive masking. This method utilizes the information obtained
      from the forepart of merged characters to predict candidates for the leftmost
      character, and then applies character-adaptive masking and character recognition
      to verifying the prediction. Therefore, the arbitrary-shaped cutting path will
      follow the right shape of the leftmost character so as to preserve the shape of
      the next character. This method handles the first two types well and greatly
      improves the segmentation accuracy of the overlapped type. The experimental
      results and the performance comparisons with other methods demonstrate the
      effectiveness of the proposed method.

PMID- 15719929
TI  - A brain-like neural network for periodicity analysis.
AB  - This paper introduces a brain-like neural model for sound processing. The
      periodicity analyzing network (PAN) is a bio-inspired neural network of spiking
      neurons. The PAN consists of complex models of neurons, which can be used for
      understanding the dynamics of individual neurons and neuronal networks. On a
      technical level, the PAN is able to compute the ratio of modulation and carrier
      frequency of harmonic sound signals. The PAN model may, therefore, be used in
      audio signal processing applications, such as sound source separation,
      periodicity analysis, and the cocktail party problem.

PMID- 15719930
TI  - Relay feedback tuning of robust PID controllers with iso-damping property.
AB  - A new tuning method for proportional-integral-derivative (PID) controller design
      is proposed for a class of unknown, stable, and minimum phase plants. We are able
      to design a PID controller to ensure that the phase Bode plot is flat, i.e., the
      phase derivative w.r.t. the frequency is zero, at a given frequency called the
      "tangent frequency" so that the closed-loop system is robust to gain variations
      and the step responses exhibit an iso-damping property. At the "tangent
      frequency," the Nyquist curve tangentially touches the sensitivity circle.
      Several relay feedback tests are used to identify the plant gain and phase at the
      tangent frequency in an iterative way. The identified plant gain and phase at the
      desired tangent frequency are used to estimate the derivatives of amplitude and
      phase of the plant with respect to frequency at the same frequency point by
      Bode's integral relationship. Then, these derivatives are used to design a PID
      controller for slope adjustment of the Nyquist plot to achieve the robustness of
      the system to gain variations. No plant model is assumed during the PID
      controller design. Only several relay tests are needed. Simulation examples
      illustrate the effectiveness and the simplicity of the proposed method for robust
      PID controller design with an iso-damping property.

PMID- 15719931
TI  - Fault tolerant control of multivariable processes using auto-tuning PID
      controller.
AB  - Fault tolerant control of dynamic processes is investigated in this paper using
      an auto-tuning PID controller. A fault tolerant control scheme is proposed
      composing an auto-tuning PID controller based on an adaptive neural network
      model. The model is trained online using the extended Kalman filter (EKF)
      algorithm to learn system post-fault dynamics. Based on this model, the PID
      controller adjusts its parameters to compensate the effects of the faults, so
      that the control performance is recovered from degradation. The auto-tuning
      algorithm for the PID controller is derived with the Lyapunov method and
      therefore, the model predicted tracking error is guaranteed to converge
      asymptotically. The method is applied to a simulated two-input two-output
      continuous stirred tank reactor (CSTR) with various faults, which demonstrate the
      applicability of the developed scheme to industrial processes.

PMID- 15719932
TI  - A region dissimilarity relation that combines feature-space and spatial
      information for color image segmentation.
AB  - This paper proposes a methodology that incorporates principles from cluster
      analysis and graph representation to achieve efficient image segmentation
      results. More specifically, a feature-based, inter-region dissimilarity relation
      is considered here in order to determine the dissimilarity matrix in a graph
      based segmentation scheme. The calculation of the dissimilarity function between
      adjacent elementary image regions is based on the proximity of each region's
      feature vector to the main clusters that are formed by the image samples in the
      feature space. In contrast to typical segmentation approaches of the literature,
      the global feature space information is included in the spatial graph
      representation that was derived from the initial Watershed partitioning. A region
      grouping process is applied next to form the final segmentation results. The
      proposed approach was also compared to approaches that use feature-based, or
      spatial information exclusively, to indicate its effectiveness.

PMID- 15719933
TI  - A primal-dual neural network for online resolving constrained kinematic
      redundancy in robot motion control.
AB  - This paper proposes a primal-dual neural network with a one-layer structure for
      online resolution of constrained kinematic redundancy in robot motion control.
      Unlike the Lagrangian network, the proposed neural network can handle physical
      constraints, such as joint limits and joint velocity limits. Compared with the
      existing primal-dual neural network, the proposed neural network has a low
      complexity for implementation. Compared with the existing dual neural network,
      the proposed neural network has no computation of matrix inversion. More
      importantly, the proposed neural network is theoretically proved to have not only
      a finite time convergence, but also an exponential convergence rate without any
      additional assumption. Simulation results show that the proposed neural network
      has a faster convergence rate than the dual neural network in effectively
      tracking for the motion control of kinematically redundant manipulators.

PMID- 15719934
TI  - PID controller design for output PDFs of stochastic systems using linear matrix
      inequalities.
AB  - This paper presents a pseudo proportional-integral-derivative (PID) tracking
      control strategy for general non-Gaussian stochastic systems based on a linear B
      spline model for the output probability density functions (PDFs). The objective
      is to control the conditional PDFs of the system output to follow a given target
      function. Different from existing methods, the control structure (i.e., the PID)
      is imposed before the output PDF controller design. Following the linear B-spline
      approximation on the measured output PDFs, the concerned problem is transferred
      into the tracking of given weights which correspond to the desired PDF. For
      systems with or without model uncertainties, it is shown that the solvability can
      be casted into a group of matrix inequalities. Furthermore, an improved
      controller design procedure based on the convex optimization is proposed which
      can guarantee the required tracking convergence with an enhanced robustness.
      Simulations are given to demonstrate the efficiency of the proposed approach and
      encouraging results have been obtained.

PMID- 15719935
TI  - Supervisory control of fuzzy discrete event systems: a formal approach.
AB  - Fuzzy discrete event systems (DESs) were proposed recently by Lin and Ying [19],
      which may better cope with the real-world problems of fuzziness, impreciseness,
      and subjectivity such as those in biomedicine. As a continuation of [19], in this
      paper, we further develop fuzzy DESs by dealing with supervisory control of fuzzy
      DESs. More specifically: 1) we reformulate the parallel composition of crisp
      DESs, and then define the parallel composition of fuzzy DESs that is equivalent
      to that in [19]. Max-product and max-min automata for modeling fuzzy DESs are
      considered, 2) we deal with a number of fundamental problems regarding
      supervisory control of fuzzy DESs, particularly demonstrate controllability
      theorem and nonblocking controllability theorem of fuzzy DESs, and thus, present
      the conditions for the existence of supervisors in fuzzy DESs; 3) we analyze the
      complexity for presenting a uniform criterion to test the fuzzy controllability
      condition of fuzzy DESs modeled by max-product automata; in particular, we
      present in detail a general computing method for checking whether or not the
      fuzzy controllability condition holds, if max-min automata are used to model
      fuzzy DESs, and by means of this method we can search for all possible fuzzy
      states reachable from initial fuzzy state in max-min automata. Also, we introduce
      the fuzzy n-controllability condition for some practical problems, and 4) a
      number of examples serving to illustrate the applications of the derived results
      and methods are described; some basic properties related to supervisory control
      of fuzzy DESs are investigated. To conclude, some related issues are raised for
      further consideration.

PMID- 15719936
TI  - Feature generation using genetic programming with application to fault
      classification.
AB  - One of the major challenges in pattern recognition problems is the feature
      extraction process which derives new features from existing features, or directly
      from raw data in order to reduce the cost of computation during the
      classification process, while improving classifier efficiency. Most current
      feature extraction techniques transform the original pattern vector into a new
      vector with increased discrimination capability but lower dimensionality. This is
      conducted within a predefined feature space, and thus, has limited searching
      power. Genetic programming (GP) can generate new features from the original
      dataset without prior knowledge of the probabilistic distribution. In this paper,
      a GP-based approach is developed for feature extraction from raw vibration data
      recorded from a rotating machine with six different conditions. The created
      features are then used as the inputs to a neural classifier for the
      identification of six bearing conditions. Experimental results demonstrate the
      ability of GP to discover autimatically the different bearing conditions using
      features expressed in the form of nonlinear functions. Furthermore, four sets of
      results--using GP extracted features with artificial neural networks (ANN) and
      support vector machines (SVM), as well as traditional features with ANN and SVM-
      have been obtained. This GP-based approach is used for bearing fault
      classification for the first time and exhibits superior searching power over
      other techniques. Additionaly, it significantly reduces the time for computation
      compared with genetic algorithm (GA), therefore, makes a more practical
      realization of the solution.

PMID- 15719938
TI  - Wavelet transform-based frequency tuning ILC.
AB  - In this paper, a discrete wavelet transform-based cutoff frequency tuning method
      is proposed and experimental investigation is reported. In the method, discrete
      wavelet packet algorithm, as a time-frequency analysis tool, is employed to
      decompose the tracking error into different frequency regions so that the maximal
      error component can be identified at any time step. At each time step, the
      passband of the filter is from zero to the upper limit of frequency region where
      the maximal error component resides. Hence, the filter is a function of time as
      well as index of cycle. The experimental results show that this method can
      suppress higher frequency error components at proper time steps. While at the
      time steps where the major tracking error falls into lower frequency range, the
      cutoff frequency of the filter is set lower to reduce the influence of noises and
      uncertainties. This way, learning transient and long-term stability can be
      improved.

PMID- 15719937
TI  - Orthogonal kernel machine for the prediction of functional sites in proteins.
AB  - A novel pattern recognition algorithm called an orthogonal kernel machine (OKM)
      is presented for the prediction of functional sites in proteins. Two novelties in
      OKM are that the kernel function is specially designed for measuring the
      similarity between a pair of protein sequences and the kernels are selected using
      the orthogonal method. Based on a set of well-recognized orthogonal kernels, this
      algorithm demonstrates its superior performance compared with other methods. An
      application of this algorithm to a real problem is presented.

PMID- 15719939
TI  - A novel neural approximate inverse control for unknown nonlinear discrete
      dynamical systems.

PMID- 15719940
TI  - Near-recursive optical flow from weighted image differences.

PMID- 15719941
TI  - Adaptive output feedback control of systems preceded by the Preisach-type
      hysteresis.

PMID- 15719942
TI  - Absolute componentwise stability of interval hopfield neural networks.

PMID- 15719943
TI  - On improvement of classification accuracy for stochastic discrimination.

PMID- 15719944
TI  - Reinforcement learning-based output feedback control of nonlinear systems with
      input constraints.

PMID- 15719945
TI  - M-estimator and D-optimality model construction using orthogonal forward
      regression.

PMID- 15719946
TI  - NRC restrictions on the packaging of radioactive material should be expressed
      more explicitly than simply in terms of "activity". For the proposition.

PMID- 15719947
TI  - NRC restrictions on the packaging of radioactive material should be expressed
      more explicitly than simply in terms of "activity". Against the proposition.

PMID- 15719948
TI  - Imaging of high-intensity focused ultrasound-induced lesions in soft biological
      tissue using thermoacoustic tomography.
AB  - An imaging technology, thermoacoustic tomograpy (TAT), was applied to the
      visualization of high-intensity focused ultrasound (HIFU)-induced lesions. A
      single, spherically focused ultrasonic transducer, operating at a central
      frequency of approximately 4 MHz, was used to generate a HIFU field in fresh
      porcine muscle. Microwave pulses from a 3-GHz microwave generator were then
      employed to generate thermoacoustic sources in this tissue sample. The
      thermoacoustic signals were detected by an unfocused ultrasonic transducer that
      was scanned around the sample. To emphasize the boundaries between the lesion and
      its surrounding tissue, a local-tomography-type reconstruction method was applied
      to reconstruct the TAT images of the lesions. Good contrast was obtained between
      the lesion and the tissue surrounding it. Gross pathologic photographs of the
      tissue samples confirmed the TAT images. This work demonstrates that TAT may
      potentially be used to image HIFU-induced lesions in biological tissues.

PMID- 15719949
TI  - The use of film dosimetry of the penumbra region to improve the accuracy of
      intensity modulated radiotherapy.
AB  - Accurate measurements of the penumbra region are important for the proper
      modeling of the radiation beam for linear accelerator-based intensity modulated
      radiation therapy. The usual data collection technique with a standard ionization
      chamber artificially broadens the measured beam penumbrae due to volume effects.
      The larger the chamber, the greater is the spurious increase in penumbra width.
      This leads to inaccuracies in dose calculations of small fields, including small
      fields or beam segments used in IMRT. This source of error can be rectified by
      the use of film dosimetry for penumbra measurements because of its high spatial
      resolution. The accuracy of IMRT calculations with a pencil beam convolution
      model in a commercial treatment planning system was examined using commissioning
      data with and without the benefit of film dosimetry of the beam penumbrae. A set
      of dose-spread kernels of the pencil beam model was calculated based on
      commissioning data that included beam profiles gathered with a 0.6-cm-i.d.
      ionization chamber. A second set of dose-spread kernels was calculated using the
      same commissioning data with the exception of the penumbrae, which were measured
      with radiographic film. The average decrease in the measured width of the 80%-20%
      penumbrae of various square fields of size 3-40 cm, at 5 cm depth in water
      equivalent plastic was 0.27 cm. Calculations using the pencil beam model after it
      was re-commissioned using film dosimetry of the penumbrae gave better agreement
      with measurements of IMRT fields, including superior reproduction of high dose
      gradient regions and dose extrema. These results show that accurately measuring
      the beam penumbrae improves the accuracy of the dose distributions predicted by
      the treatment planning system and thus is important when commissioning beam
      models used for IMRT.

PMID- 15719950
TI  - Predicting radiotherapy-induced cardiac perfusion defects.
AB  - The purpose of this work is to compare the efficacy of mathematical models in
      predicting the occurrence of radiotherapy-induced left ventricular perfusion
      defects assessed using single-photon emission computed tomography (SPECT). The
      basis of this study is data from 73 left-sided breast/ chestwall patients treated
      with tangential photon fields. The mathematical models compared were three
      commonly used parametric models [Lyman normal tissue complication probability
      (LNTCP), relative serialty (RS), generalized equivalent uniform dose (gEUD)] and
      a nonparametric model (Linear discriminant analysis--LDA). Data used by the
      models were the left ventricular dose--volume histograms, or SPECT-based dose
      function histograms, and the presence/absence of SPECT perfusion defects 6 months
      postradiation therapy (21 patients developed defects). For the parametric models,
      maximum likelihood estimation and F-tests were used to fit the model parameters.
      The nonparametric LDA model step-wise selected features (volumes/function above
      dose levels) using a method based on receiver operating characteristics (ROC)
      analysis to best separate the groups with and without defects. Optimistic (upper
      bound) and pessimistic (lower bound) estimates of each model's predictive
      capability were generated using ROC curves. A higher area under the ROC curve
      indicates a more accurate model (a model that is always accurate has area = 1).
      The areas under these curves for different models were used to statistically test
      for differences between them. Pessimistic estimates of areas under the ROC curve
      using dose-volume histogram/ dose-function histogram inputs, in order of
      increasing prediction accuracy, were LNTCP (0.79/0.75), RS (0.80/0.77), gEUD
      (0.81/0.78), and LDA (0.84/0.86). Only the LDA model benefited from SPECT-based
      regional functional information. In general, the LDA model was statistically
      superior to the parametric models. The LDA model selected as features the left
      ventricular volumes above approximately 23 Gy (V23), essentially volume in field,
      and 33 Gy (V33), as best separating the groups with and without defects. In
      conclusion, the nonparametric LDA model appears to be a more accurate predictor
      of radiotherapy-induced left ventricular perfusion defects than commonly used
      parametric models.

PMID- 15719951
TI  - Monte Carlo and experimental derivation of TG43 dosimetric parameters for CSM
      type Cs-137 sources.
AB  - In this study, complete dosimetric datasets for the CSM2 and CSM3 Cs-137 sources
      were obtained using the Monte Carlo GEANT4 code. The application of this
      calculation method was experimentally validated with thermoluminescent dosimetry
      (TLD). Functions and parameters following the TG43 formalism are presented: the
      dose rate constant, the radial dose functional, and the anisotropy function. In
      addition, to aid the quality control process on treatment planning systems, a two
      dimensional (2D) rectangular dose rate table (the traditional along-away table),
      coherent with the TG43 dose calculation formalism, is given. The data given in
      this study complement existing information for both sources on the following
      aspects: (i) the source asymmetries were considered explicitly in the Monte Carlo
      calculations, (ii) TG43 data were derived directly from Monte Carlo calculations,
      (iii) the radial range of the different tables was increased as well as the
      angular resolution in the anisotropy function, including angles close to the
      longitudinal source axis. The CSM2 source TG-43 data of Liu et al. [Med. Phys.
      31, 477-483 (2004)] are not consistent with the Williamson 2D along-away data
      [Int. J. Radiat. Oncol., Biol., Phys. 15, 227-237 (1988)] at distances closer
      than approximately 2 cm from the source. The data presented here for this source
      are consistent with this 2D along-away table, and are suitable for use in
      clinical practice.

PMID- 15719952
TI  - The role of nonelastic reactions in absorbed dose distributions from therapeutic
      proton beams in different medium.
AB  - Many new techniques for delivering radiation therapy are being developed for the
      treatment of cancer. One of these, proton therapy, is becoming increasingly
      popular because of the precise way in which protons deliver dose to the tumor
      volume. In order to achieve this level of precision, extensive treatment planning
      needs to be carried out to determine the optimum beam energies, energy spread
      (which determines the width of the spread-out Bragg peak), and angles for each
      patient's treatment. Due to the level of precision required and advancements in
      computer technology, there is increasing interest in the use of Monte Carlo
      calculations for treatment planning in proton therapy. However, in order to
      achieve optimum simulation times, nonelastic nuclear interactions between protons
      and the target nucleus within the patient's internal structure are often not
      accounted for or are simulated using less accurate models such as analytical or
      ray tracing. These interactions produce high LET particles such as neutrons,
      alpha particles, and recoil protons, which affect the dose distribution and
      biological effectiveness of the beam. This situation has prompted an
      investigation of the importance of nonelastic products on depth dose
      distributions within various materials including water, A-150 tissue equivalent
      plastic, ICRP (International Commission on Radiological Protection) muscle, ICRP
      bone, and ICRP adipose. This investigation was conducted utilizing the GEANT4.5.2
      Monte Carlo hadron transport toolkit.

PMID- 15719953
TI  - Filtered backprojection formula for exact image reconstruction from cone-beam
      data along a general scanning curve.
AB  - Recently, Katsevich proved a filtered backprojection formula for exact image
      reconstruction from cone-beam data along a helical scanning locus, which is an
      important breakthrough since 1991 when the spiral cone-beam scanning mode was
      proposed. In this paper, we prove a generalized Katsevich's formula for exact
      image reconstruction from cone-beam data collected along a rather flexible curve.
      We will also give a general condition on filtering directions. Based on this
      condition, we suggest a natural choice of filtering directions, which is more
      convenient than Katsevich's choice and can be applied to general scanning curves.
      In the derivation, we use analytical techniques instead of geometric arguments.
      As a result, we do not need the uniqueness of the PI lines. In fact, our formula
      can be used to reconstruct images on any chord as long as a scanning curve runs
      from one endpoint of the chord to the other endpoint. This can be considered as a
      generalization of Orlov's classical theorem. Specifically, our formula can be
      applied to (i) nonstandard spirals of variable radii and pitches (with PI- or n
      PI-windows), and (ii) saddlelike curves.

PMID- 15719955
TI  - Correction of XRII geometric distortion using a liquid-filled grid and image
      subtraction.
AB  - X-ray image intensifier (XRII) geometric distortion reduces the accuracy of image
      guided procedures and quantitative image reconstructions. Due to the dependence
      of this error on the earth's magnetic field, the required correction is angle
      dependent, and calibration data should ideally be acquired simultaneously with
      clinical image data, at a specific orientation. We describe a technique to
      correct XRII geometric image distortion at any angular position during a
      stereotactic procedure. This approach uses a machined plastic grid, which
      contains channels that can be filled with iodinated contrast agent and
      subsequently flushed with water, providing contrast and mask images,
      respectively, of a geometric calibration grid. The standard image subtraction
      capabilities of conventional digital subtraction angiography devices can then be
      used to create a subtraction image of the iodine-filled channels, without any
      confounding anatomical structure. Grid-line intersection points are used to
      determine the control points that are required for a global polynomial correction
      algorithm, creating a correction map that is specific to the current angular
      position and XRII field of view (FOV). Tests with a clinical C-arm based XRII
      show that control points can be obtained with a precision of +/-0.053 mm,
      resulting in geometric correction accuracy of +/-0.152 mm, at a nominal FOV of 40
      cm. While the precision and accuracy are both poorer than that achieved with a
      high-contrast steel-bead grid, the fact that the liquid grid can remain rigidly
      attached to the XRII during an entire procedure results in the establishment of
      an absolute detector coordinate system (referenced to the liquid-filled
      correction grid). The design of the liquid-filled channels allows the required
      control points to be introduced into the image or removed in about 30 s, avoiding
      the appearance of obscuring or confounding markers during clinical image
      acquisition, with a concurrent increase in patient dose of about 8% in the
      current design. Applications for this technique include stereotactic surgery,
      radiosurgery, x-ray stereogrammetry, and other image-guided procedures.

PMID- 15719954
TI  - Compact monochromatic flash x-ray generator utilizing a disk-cathode molybdenum
      tube.
AB  - The high-voltage condensers in a polarity-inversion two-stage Marx surge
      generator are charged from -50 to -70 kV by a power supply, and the electric
      charges in the condensers are discharged to an x-ray tube after closing gap
      switches in the surge generator with a trigger device. The x-ray tube is a
      demountable diode, and the turbo molecular pump evacuates air from the tube with
      a pressure of approximately 1 mPa. Clean molybdenum Kalpha lines are produced
      using a 20 microm-thick zirconium filter, since the tube utilizes a disk cathode
      and a rod target, and bremsstrahlung rays are not emitted in the opposite
      direction to that of electron acceleration. At a charging voltage of -70 kV, the
      instantaneous tube voltage and current were 120 kV and 1.0 kA, respectively. The
      x-ray pulse widths were approximately 70 ns, and the generator produced
      instantaneous number of Kalpha photons was approximately 3 x 10(7) photons/cm2
      per pulse at 0.5 m from the source of 3.0 mm in diameter.

PMID- 15719956
TI  - Real-time 3D surface-image-guided beam setup in radiotherapy of breast cancer.
AB  - We describe an approach for external beam radiotherapy of breast cancer that
      utilizes the three-dimensional (3D) surface information of the breast. The
      surface data of the breast are obtained from a 3D optical camera that is rigidly
      mounted on the ceiling of the treatment vault. This 3D camera utilizes light in
      the visible range therefore it introduces no ionization radiation to the patient.
      In addition to the surface topographical information of the treated area, the
      camera also captures gray-scale information that is overlaid on the 3D surface
      image. This allows us to visualize the skin markers and automatically determine
      the isocenter position and the beam angles in the breast tangential fields. The
      field sizes and shapes of the tangential, supraclavicular, and internal mammary
      gland fields can all be determined according to the 3D surface image of the
      target. A least-squares method is first introduced for the tangential-field setup
      that is useful for compensation of the target shape changes. The entire process
      of capturing the 3D surface data and subsequent calculation of beam parameters
      typically requires less than 1 min. Our tests on phantom experiments and patient
      images have achieved the accuracy of 1 mm in shift and 0.5 degrees in rotation.
      Importantly, the target shape and position changes in each treatment session can
      both be corrected through this real-time image-guided system.

PMID- 15719957
TI  - Compensation of magnetic field distortions from paramagnetic instruments by added
      diamagnetic material: measurements and numerical simulations.
AB  - In minimally invasive procedures guided by magnetic resonance (MR) imaging
      instruments usually are made of titanium or titanium alloys (e.g., nitinol),
      because other more MR-compatible materials often cannot provide sufficient
      mechanical properties. Artifacts depending on susceptibility arise in MR images
      due to incorrect spatial encoding and intravoxel dephasing and thereby hamper the
      surgeon's view onto the region of interest. To overcome the artifact problem,
      compensation of the paramagnetic properties by diamagnetic coating or filling of
      the instruments has been proposed in the literature. We used a numerical modeling
      procedure to estimate the effect of compensation. Modeling of the perturbation of
      the static magnetic field close to the instruments reflects the underlying
      problem and is much faster and cost efficient than manufacturing prototypes and
      measuring artifact behavior of these prototypes in the MR scanner. A numerical
      model based on the decomposition of the susceptibility distribution in elementary
      dipoles was developed by us. The program code was written object oriented to
      allow for both maximum computational speed and minimum random access memory. We
      used System International units throughout the modeling for the magnetic field,
      allowing absolute quantification of the magnetic field disturbance. The field
      outside a simulated needlelike instrument, modeled by a paramagnetic cylinder
      (out of titan, chi =181.1) of length 8.0 mm and of diameter 1.0 mm, coated with a
      diamagnetic layer (out of bismuth, chi=-165.0) of thickness 0, 0.1, 0.2, 0.3, and
      0.4 mm, was found to be best compensated if the cross-sectional area of the
      cylinder, multiplied by the absolute susceptibility value of the cylinder
      material, is equal to the cross-sectional area of the coating, multiplied by the
      absolute susceptibility value of the coating material. At the extremity of the
      coated cylinder an uncompensated field distortion was found to remain. We studied
      various tip shapes and geometries using our computational model: Suitable
      diamagnetic coating or filling of paramagnetic instruments clearly reduced tip
      artifacts and diminished the dependency of artifact size on orientation of the
      instrument with respect to B0 in the numerical studies. We verified the results
      of the simulations by measuring coated and uncoated titanium wires in a 1.5 T MR
      scanner.

PMID- 15719958
TI  - A stylized computational model of the head for the reference Japanese male.
AB  - Computational models of human anatomy, along with Monte Carlo radiation transport
      simulations, have been used by Snyder et al. [MIRD Pamphlet No. 5, revised (The
      Society of Nuclear Medicine, New York, 1978)], Cristy and Eckerman [ORNL/TM
      8381/VI, Oak Ridge National Laboratory, Oak Ridge, TN (1987)] and Zubal et al.
      [Med. Phys. 21, 299-302 (1994)] to estimate internal organ doses from internal
      and external radiation sources. These were created using physiological data from
      Caucasoid subjects but not from other races. There is a need for research to
      determine whether the obvious differences from the Caucasoid anatomy make these
      models unsuitable for estimating the absorbed dose in other races such as the
      Mongoloid. We used the cranial region of the adult Japanese male to represent the
      Mongoloid race. This region contains organs that are highly sensitive to
      radiation. The cranial region of a physical phantom produced by KYOTO KAGAKU Co.,
      LTD. using numerical data from a Japanese Reference Man [Tanaka, Nippon Acta.
      Radiol. 48, 509-513 (1988)] was used to supply the data for the geometry of a
      stylized computational model. Our computational model was constructed with
      equations rather than voxel-based, in order to deal with as small a number of
      parameters as possible in the computer simulation experiment. The accuracy of our
      computational model was checked by comparing simulated experimental results
      obtained with MCNP4C with actual doses measured with thermoluminescence
      dosimeters (TLDs) inside the physical phantom from which our computational model
      was constructed. The TLDs, whose margin of error is less than +/-10%, were
      arranged at six positions. Co-60 was used as the radiation source. The irradiated
      dose was 2 Gy in terms of air kerma. In the computer simulation experiments, we
      used our computational model and Cristy's computational model, whose component
      data are those of the tissue substitute materials and of the human body as
      published in ICRU Report 46. The observed absorbed dose values (Gy) at all six
      points were calculated as the percentage difference between MCNP4C simulation and
      the TLDs. In our computational model, the average values of all the percentage
      differences were 6.0+/-4.0% (tissue substitute materials) and 7.6+/-6.6% (ICRU
      Report 46), respectively. In Cristy's model, the corresponding values were 20.4+/
      3.8% (tissue substitute materials) and 21.0+/-4.1% (ICRU Report 46),
      respectively. Considering the margin of error in the radiation sensitivity of the
      TLDs, this study validates our computational model as a test object for radiation
      dosimetry studies.

PMID- 15719959
TI  - Is thermal scanner losing its bite in mass screening of fever due to SARS?
AB  - Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by
      a coronavirus. Screening to detect a potential SARS infected person plays an
      important role in preventing the spread of SARS. The use of infrared thermal
      imaging cameras has been proposed as a noninvasive, speedy, cost effective and
      fairly accurate means for mass blind screening of potential SARS infected
      persons. Infrared thermography provides a digital image showing temperature
      patterns. This has been previously utilized in the detection of inflammation and
      nerve dysfunctions. It is believed that IR cameras can potentially be used to
      detect subjects with fever, the cardinal symptom of SARS, and avian influenza.
      The accuracy of the infrared system can, however, be affected by human,
      environmental, and equipment variables. It is also limited by the fact that the
      thermal imager measures the skin temperature and not the core body temperature.
      As known, the body determines a temperature as its so-called "set point" at any
      one time during the body temperature regulation. Fever happens if the
      hypothalamus detects pyrogens and then raises the set point. The time course of a
      typical fever can be divided into three stages. When the fever initiates, the
      body attempts to raise its temperature but vasoconstriction occurs to prevent
      heat loss through the skin. With this reason, some individuals at this stage of
      fever (at the rising slope and immediately after fever begins or falling slope
      after the fever breaks) will not be detected by the scanner if it is not designed
      to detect subject at the plateau of the fever (with her/his high core
      temperature) in particular. This paper aims to study the effectiveness of
      infrared systems for its application in mass blind screening to detect subjects
      with elevated body temperature. For this application, it is critical for thermal
      imagers to be able to identify febrile from normal subjects accurately.
      Minimizing the number of false positive and false negative cases, improves the
      efficiency of the screening stations. False negative results should be avoided at
      all costs, as letting a SARS infected person through the screening process may
      result in potentially catastrophic results. Various statistical methods such as
      linear regression, Receiver Operating Characteristics analysis, and neural
      networks based classification were used to analyze the temperature data collected
      from various sites on the face on both the frontal and side profiles. Two
      important conclusions were drawn from the analysis: the best region on the face
      to obtain temperature readings and the optimal preset threshold temperature for
      the thermal imager. To conclude, the current research application will remain an
      interest and useful for reference by both local and overseas manufacturers of
      thermal scanners, users, and various government and private establishments. As
      elevation of body temperature is a common presenting symptom for many illnesses
      including infectious diseases, thermal imagers are useful tools for mass
      screening of body temperature not only for SARS but also during other public
      health crisis where widespread transmission of infection is a concern.

PMID- 15719960
TI  - Novel methods of measuring single scan dose profiles and cumulative dose in CT.
AB  - Computed tomography dose index (CTDI) is a conventional indicator of the patient
      dose in CT studies. It is measured as the integration of the longitudinal single
      scan dose profile (SSDP) by using a 100-mm-long pencil ionization chamber and a
      single axial scan. However, the assumption that most of the SSDP is contained
      within the chamber length may not be valid even for thin slices. We have measured
      the SSDPs for several slice widths on two CT scanners using a PTW diamond
      detector placed in a 300 mm x 200 mm x 300 mm water-equivalent plastic phantom.
      One SSDP was also measured using lithium fluoride (LiF) TLDs and an IC-10 small
      volume ion chamber, verifying the general shape of the SSDP measured using the
      diamond detector. Standard cylindrical PMMA CT phantoms (140 mm length) were also
      used to qualitatively study the effects of phantom shape, length, and composition
      on the measured SSDP. The SSDPs measured with the diamond detector in the water
      equivalent phantom were numerically integrated to calculate the relative
      accumulated dose D(L)(0)calc at the center of various scan lengths L. D(L)(0)calc
      reached an equilibrium value for L > 300 mm, suggesting the need for phantoms
      longer than standard CT dose phantoms. We have also measured the absolute
      accumulated dose using an IC-10 small volume ion chamber, D(L)(0)SV, at three
      points in the phantom cross section for several beamwidths and scan lengths. For
      one CT system, these measurements were made in both axial and helical scanning
      modes. The absolute CTDI100, measured with a 102 mm active length pencil chamber,
      were within 4% of D(L)(0)SV measured with the small volume ion chamber for L
      approximately 100 mm suggesting that nonpencil chambers can be successfully used
      for CT dosimetry. For nominal beam widths ranging from 3 to 20 mm and for L
      approximately 250 mm, D(L)(0)SV values at the center of the water-equivalent
      phantom's elliptic cross section were approximately 25%-30% higher than the
      measured CTDI100. For small beamwidths, the difference in D(L)(0)SV for L
      approximately 250 mm and L approximately 14 x beamwidth (CTDI14nT) reached up to
      50%. Peripheral point doses at 70 mm depth along the major axis of the phantom
      for L approximately 250 mm were up to 22% higher than for L approximately 100 mm.
      The differences between CTDI100 and D(L)(0)SV for L approximately 250 mm were in
      good agreement with the predictions made from the numerical integration of the
      measured SSDPs. Due to the considerable dose measured beyond the length of
      standard CT phantoms, CT dosimetry for longer body scan series should be
      performed in longer phantoms. Measurements could be made as we have shown, using
      a small volume chamber translating through the beam using multiple scans.

PMID- 15719961
TI  - Dosimetric evaluation of a new design MOSFET in vivo dosimeter.
AB  - A single-use dosimeter, designed for in vivo patient dosimetry, has been
      evaluated. Key dosimetric characteristics of the dosimetry system have been
      measured for high-energy photon and electron beams commonly used in external beam
      therapy. Under the measurement conditions utilized, dose accuracy was within 5%
      for all data points, and inter-batch uniformity was acceptable, with a standard
      deviation of 1.7%. Dose linearity was confirmed for doses ranging from 2 to 400
      cGy. The dosimeter readings were independent of dose rate for rates ranging from
      80 to 480 cGy/min. When used as instructed, the dosimeter readings were accurate
      across the tested range of energy and modality. These measurements show that the
      dosimetry system's performance may be acceptable for in vivo dosimetry of
      entrance d(max) doses.

PMID- 15719962
TI  - Motion-encoded dose calculation through fluence/sinogram modification.
AB  - Conventional radiotherapy treatment planning systems rely on a static computed
      tomography (CT) image for planning and evaluation. Intra/inter-fraction patient
      motions may result in significant differences between the planned and the
      delivered dose. In this paper, we develop a method to incorporate the knowledge
      of intra/inter-fraction patient motion directly into the dose calculation. By
      decomposing the motion into a parallel (to beam direction) component and
      perpendicular (to beam direction) component, we show that the motion effects can
      be accounted for by simply modifying the fluence distribution (sinogram). After
      such modification, dose calculation is the same as those based on a static
      planning image. This method is superior to the "dose-convolution" method because
      it is not based on "shift invariant" assumption. Therefore, it deals with
      material heterogeneity and surface curvature very well. We test our method using
      extensive simulations, which include four phantoms, four motion patterns, and
      three plan beams. We compare our method with the "dose-convolution" and the
      "stochastic simulation" methods (gold standard). As for the homogeneous flat
      surface phantom, our method has similar accuracy as the "dose-convolution"
      method. As for all other phantoms, our method outperforms the "dose-convolution."
      The maximum motion encoded dose calculation error using our method is within 4%
      of the gold standard. It is shown that a treatment planning system that is based
      on "motion-encoded dose calculation" can incorporate random and systematic motion
      errors in a very simple fashion. Under this approximation, in principle, a
      planning target volume definition is not required, since it already accounts for
      the intra/inter-fraction motion variations and it automatically optimizes the
      cumulative dose rather than the single fraction dose.

PMID- 15719963
TI  - Temporal performance of amorphous selenium mammography detectors.
AB  - We investigated temporal performance of amorphous selenium (a-Se) detectors
      specifically designed for mammographic imaging. Our goal is to quantify the
      inherent lag and ghosting of a-Se photoconductor as a function of imaging
      conditions. Two small area electroded a-Se samples, one positively and the other
      negatively biased on the entrance side of x rays, were used in the experiments.
      The study of lag and ghosting was performed by delivering a number of raw
      exposures as experienced in screening mammography to the samples at different
      electric field strength E(Se) while measuring the current through the a-Se
      sample. Ghosting at different operational conditions was quantified as the
      percentage x-ray sensitivity (x-ray generated photocurrent measured from the
      sample) reduction compared to before irradiation. Lag was determined by measuring
      the residual current of a-Se at a given time after the end of each x-ray
      exposure. Both lag and ghosting were measured as a function of E(Se) and
      cumulative exposure. The values of E(Se) used in our experiments ranged from 1 to
      20 V/microm. It was found that ghosting increases with exposure and decreases
      with E(Se) for both samples because of the dominant effect of recombination
      between trapped electrons and x-ray generated holes. Lag on the other hand has
      different dependence on E(Se) and cumulative exposure. At E(Se) < or = 10
      V/microm, the first frame lag for both samples changed slowly with cumulative
      exposure, with a range of 0.2%-1.7% for the positively biased sample and 0.5%-8%
      for the negatively biased sample. Overall the positively biased sample has better
      temporal performance than the negatively biased sample due to the lower density
      of trapped electrons. The impact of time interval between exposures on the
      temporal performance was also investigated. Recovery of ghosting with longer time
      interval was observed, which was attributed to the neutralization of trapped
      electrons by injected holes through dark current.

PMID- 15719964
TI  - Reference photon dosimetry data and reference phase space data for the 6 MV
      photon beam from varian clinac 2100 series linear accelerators.
AB  - The current study presents the reference photon dosimetry data (RPDD) and
      reference phase space data (RPSD) for the 6 MV photon beam from Varian 2100
      series linear accelerators. The RPDD provide the basic photon dosimetry data,
      typically collected during the initial commissioning of a new linear accelerator,
      including output factors, depth dose data, and beam profile data in air and in
      water. The RPSD provide the full phase space information, such as position,
      direction, and energy for each particle generated inside the head of any
      particular linear accelerator in question. The dosimetric characteristics if the
      6 MV photon beam from the majority of the aforementioned accelerators, which are
      unaltered from the manufacturer's original specifications, can be fully described
      with these two data sets within a clinically acceptable uncertainty
      (approximately +/-2 %). The current study also presents a detailed procedure to
      establish the RPDD and RPSD using measured data and Monte Carlo calculations. The
      RPDD were constructed by compiling our own measured data and the average data
      based on the analysis of more than 50 sets of measured data from the Radiological
      Physics Center (RPC) and 10 sets of clinical dosimetry data obtained from 10
      different institutions participating in the RPC's quality assurance monitoring
      program. All the measured data from the RPC and the RPC-monitored institutions
      were found to be within a statistically tight range (i.e., 1sigma approximately
      1% or less) for each dosimetric quantity. The manufacturer's standard data,
      except for in-air off-axis factors that are available only from the current
      study, were compared with the RPDD, showing that the manufacturer's standard data
      could also be used as the RPDD for the photon beam studied in this study. The
      RPSD were obtained from Monte Carlo calculations using the BEAMnrc/ DOSXYZnrc
      code system with 6.2 MeV (a spread of 3% full width at half maximum) and 1.0 mm
      full width at half maximum as the values of the energy and radial spread of a
      Gaussian electron pencil beam incident on the target, respectively. The RPSD were
      capable of generating Monte Carlo data that agreed with the RPDD within the
      acceptance criteria adopted in the current study (e.g., 1% or 1 mm for depth
      dose). A complete set of the RPDD and RPSD from the current study is available
      from the RPC website (http://rpc.mdanderson.org) or via mass storage media such
      as DVD or CD-ROM upon request.

PMID- 15719966
TI  - Detection of IMRT delivery errors using a quantitative 2D dosimetric verification
      system.
AB  - We investigated the feasibility of detecting intensity modulated radiotherapy
      delivery errors automatically using a scalar evaluation of two-dimensional (2D)
      transverse dose measurement of the complete treatment delivery. Techniques using
      the gamma index and the normalized agreement test (NAT) index were used to
      parametrize the agreement between measured and computed dose distributions to
      seven different scalar metrics. Simulated verifications with delivery errors
      calculated using a commercially available treatment planning system for 9
      prostate and 7 paranasal sinus cases were compared to 433 clinical verifications.
      The NAT index with 5% and 3 mm criteria that included cold areas outside the
      planning target volume detected the largest percent of delivery errors. Assuming
      a false positive rate of 5%, it was able to detect 88% of beam energy changes,
      94% of a different patient's plan being delivered, 25% of plans with one beam's
      collimator rotated by 90 degrees, 81% of rotating one beam's gantry angle by 10
      degrees, and 100% of omitting the delivery of one beam. However, no instances of
      changing one beam's monitor unit setting by 10% or shifting the isocenter by 5 mm
      were detected. Although the phantom shift could not be detected by the small
      change it made in the dose distribution, our autopositioning algorithm clearly
      identified the spatial anomaly. Using tighter 3 %/2 mm criteria or combining dose
      and distance disagreements in an either/or fashion resulted in poorer delivery
      error detection. The mean value of the 2D gamma index distribution was less
      sensitive to delivery errors than the other scalar metrics studied. Although we
      found that scalar metrics do not have sufficient delivery error detection rates
      to be used as the sole clinical analysis technique, manually examining 2D dose
      comparison images would result in a near 100% detection rate while performing an
      ion chamber measurement alone would only detect 54% of these errors.

PMID- 15719967
TI  - Sliding slice: a novel approach for high accuracy and automatic 3D localization
      of seeds from CT scans.
AB  - We present a conceptually novel principle for 3D reconstruction of prostate seed
      implants. Unlike existing methods for implant reconstruction, the proposed
      algorithm uses raw CT data (sinograms) instead of reconstructed CT slices. Using
      raw CT data solves several inevitable problems related to the reconstruction from
      CT slices. First, the sinograms are not affected by reconstruction artifacts in
      the presence of metallic objects and seeds in the patient body. Second, the
      scanning axis is not undersampled as in the case of CT slices; as a matter of
      fact the scanning axis is the most densely sampled and each seed is typically
      represented by several hundred samples. Moreover, the shape of a single seed in a
      sinogram can be modeled exactly, thus facilitating the detection. All this allows
      very accurate 3D reconstruction of both position and the orientation of the
      seeds. Preliminary results indicate that the seed position can be estimated with
      0.15 mm accuracy (average), while the orientation estimate accuracy is within 3
      deg on average. Although the main contribution of the paper is to present a new
      principle of reconstruction, a preliminary implementation is also presented as a
      proof of concept. The implemented algorithm has been tested on a phantom and the
      obtained results are presented to validate the proposed approach.

PMID- 15719965
TI  - Reduction of exposure of newborns and caregivers to very high electromagnetic
      fields produced by incubators.
AB  - The aims of this paper is to measure whether ferromagnetic panels sufficiently
      reduce the high electromagnetic fields (EMF) to which newborns are exposed in
      incubators and to which caregivers are exposed when working near the incubators.
      We measured EMF at mattress level in three neonatal incubators with and without
      ferromagnetic panels between the electric motor and the mattress. We then
      measured the EMF at the level of the maximum emission point for caregivers, i.e.,
      near the display panel. The ferromagnetic panels were (a) 5 mm thick iron, (b),
      (c), (d) respectively, one, two, and three sheets of 0.3 mm thick mu-metal. The
      weight of iron sheet was 4 g/cm2, and mu-metal 0.2 g/cm2. The use of the
      ferromagnetic panels significantly reduced the EMF. No significant difference in
      attenuation was recorded using one, two, or, three sheets of mu-metal, or a
      single sheet of iron. One, two, and three sheets of mu-metal reduced EMFs by 77%,
      82%, and 84.3%, respectively; the reduction with iron was 80%. EMF values
      measured in incubators were higher than those to which the general population is
      exposed. The use of ferromagnetic panels significantly reduces the level of EMFs
      to which neonates and caregivers are exposed.

PMID- 15719968
TI  - Respiration-correlated treatment delivery using feedback-guided breath hold: a
      technical study.
AB  - Respiratory motion causes movement of internal structures in the thorax and
      abdomen, making accurate delivery of radiation therapy to tumors in those areas a
      challenge. To reduce the uncertainties caused by this motion, we have developed
      feedback-guided breath hold (FGBH), a novel delivery technique in which radiation
      is delivered only during a voluntary breath hold that is sustained for as long as
      the patient feels comfortable. Here we present the technical aspects of FGBH,
      which involve (1) fabricating the hardware so the respiratory trace can be
      displayed to the patient, (2) assembling a delay box to be used as a breath-hold
      detector, and (3) performing quality control tests to ensure that FGBH can be
      delivered accurately and safely. A commercial respiratory tracking system that
      uses an external fiducial to monitor abdominal wall motion generates and displays
      the breathing trace and specific positions in the breathing cycle where a breath
      hold needs to occur. Hardware was developed to present this display to the
      patient in the treatment position. Patients view the presentation either on a
      liquid crystal display or through a pair of virtual reality goggles. Using the
      respiratory trace as a visual aid, the patient performs a breath hold so that the
      position representing the location of a fiducial is held within a specified
      gating window. A delay box was fabricated to differentiate between gating signals
      received during free breathing and those received during breath hold, allowing
      radiation delivery only when the fiducial was within the breath-hold gating
      window. A quality control analysis of the gating delay box and the integrated
      system was performed to ensure that all of the hardware and components were ready
      for clinical use.

PMID- 15719969
TI  - Visibility of simulated microcalcifications--a hardcopy-based comparison of three
      mammographic systems.
AB  - Full-field digital mammography systems are currently available for clinical use.
      These digital systems offer improved image quality, flexible image processing,
      display, storage, retrieval, and transmission. These systems employ a variety of
      different x-ray detectors based on storage phosphors (in computed radiography),
      charge-coupled devices (CCDs), or amorphous silicon flat panels (FPs). The
      objective of this study is to compare three different types of mammographic
      detectors: screenfilm (SF) combination, a CsI-based FP detector, a CCD and x-ray
      phosphor-based detector for their performance in detection of simulated
      microcalcifications. Microcalcifications (MCs) were simulated with calcium
      carbonate grains of various sizes (90-355 microm). They were overlapped with a
      slab of simulated 50% adipose/50% glandular breast tissue for a uniform
      background or an anthropomorphic breast phantom for a tissue structure
      background. Images of the phantoms, acquired with and without magnification, were
      reviewed by mammographers, physicists, and students. A five-point confidence
      level rating was given for each MC reviewed. Average ratings from the
      mammographers were used to compare the performances of the three imaging systems,
      various MC size groups, and two magnification modes. The results indicate that
      with uniform background and no magnification, the FP system performed the best
      while the SF system did slightly better than the CCD system. With magnification
      added, all detection tasks were improved except for the smallest and largest one
      or two size groups. In particular, detection in the SF and CCD images was
      significantly improved over that in the FP images. With tissue structure
      background and no magnification, the FP system was outperformed by the SF and the
      CCD systems. With magnification added, the performance of the FP and the CCD
      systems was improved significantly. With this improvement, the SF and FP systems
      were outperformed by the CCD system.

PMID- 15719970
TI  - Patient specific optimization of the relation between CT-hounsfield units and
      proton stopping power with proton radiography.
AB  - The purpose of this work is to show the feasibility of using in vivo proton
      radiography of a radiotherapy patient for the patient individual optimization of
      the calibration from CT-Hounsfield units to relative proton stopping power. Water
      equivalent tissue (WET) calibrated proton radiographs of a dog patient treated
      for a nasal tumor were used as baseline in comparison with integrated proton
      stopping power through the calibrated CT of the dog. In an optimization procedure
      starting with a stoichiometric calibration curve, the calibration was modified
      randomly. The result of this iteration is an optimized calibration curve which
      was used to recalculate the dose distribution of the patient. One result of this
      experiment was that the mean value of the deviations between WET calculations
      based on the stoichiometric calibration curve and the measurements was shifted
      systematically away from zero. The calibration produced by the optimization
      procedure reduced this shift to around 0.4 mm. Another result was that the
      precision of the calibration, reflected as the standard deviation of the normally
      distributed deviations between WET calculation and measurement, could be reduced
      from 7.9 to 6.7 mm with the optimized calibration. The dose distributions based
      on the two calibration curves showed major deviations at the distal end of the
      target volume.

PMID- 15719971
TI  - Theoretical study of the influence of a heterogeneous activity distribution on
      intratumoral absorbed dose distribution.
AB  - Radioimmunotherapy of hematopoeitic cancers and micrometastases has been shown to
      have significant therapeutic benefit. The treatment of solid tumors with
      radionuclide therapy has been less successful. Previous investigations of
      intratumoral activity distribution and studies on intratumoral drug delivery
      suggest that a probable reason for the disappointing results in solid tumor
      treatment is nonuniform intratumoral distribution coupled with restricted
      intratumoral drug penetrance, thus inhibiting antineoplastic agents from reaching
      the tumor's center. This paper describes a nonuniform intratumoral activity
      distribution identified by limited radiolabeled tracer diffusion from tumor
      surface to tumor center. This activity was simulated using techniques that
      allowed the absorbed dose distributions to be estimated using different
      intratumoral diffusion capabilities and calculated for tumors of varying
      diameters. The influences of these absorbed dose distributions on solid tumor
      radionuclide therapy are also discussed. The absorbed dose distribution was
      calculated using the dose point kernel method that provided for the application
      of a three-dimensional (3D) convolution between a dose rate kernel function and
      an activity distribution function. These functions were incorporated into 3D
      matrices with voxels measuring 0.10 x 0.10 x 0.10 mm3. At this point fast Fourier
      transform (FFT) and multiplication in frequency domain followed by inverse FFT
      (iFFT) were used to effect this phase of the dose calculation process. The
      absorbed dose distribution for tumors of 1, 3, 5, 10, and 15 mm in diameter were
      studied. Using the therapeutic radionuclides of 131I, 186Re, 188Re, and 90Y, the
      total average dose, center dose, and surface dose for each of the different tumor
      diameters were reported. The absorbed dose in the nearby normal tissue was also
      evaluated. When the tumor diameters exceed 15 mm, a much lower tumor center dose
      is delivered compared with tumors between 3 and 5 mm in diameter. Based on these
      findings, the use of higher beta-energy radionuclides, such as 188Re and 90Y is
      more effective in delivering a higher absorbed dose to the tumor center at tumor
      diameters around 10 mm.

PMID- 15719972
TI  - Dynamic, three-dimensional optical tracking of an ablative laser beam.
AB  - Surgical resection remains the treatment of choice for brain tumors with
      infiltrating margins but is currently limited by visual discrimination between
      normal and neoplastic marginal tissues during surgery. Imaging modalities such as
      computed tomography, magnetic resonance, positron emission tomography, and
      optical techniques can accurately localize tumor margins. We believe coupling the
      fine resolution of current imaging techniques with the precise cutting of
      midinfrared lasers through image-guided neurosurgery can greatly enhance tumor
      margin resection. This paper describes a feasibility study designed to optically
      track in three-dimensional space the articulated arm delivery of a noncontact
      ablative laser beam. To enable optical tracking of the laser beam focus, infrared
      emitting diodes (IREDs) were attached to a handpiece machined for the distal end
      of the articulated arm of a surgical carbon dioxide laser. Crosstalk between the
      ablative laser beam and the tracking diodes was measured. The geometry of the
      adapted laser handpiece was characterized to track an externally attached passive
      tip and the laser beam focus. Target localization accuracies were assessed for
      both instrument points-of-interest and the sources of tracking errors were
      investigated. Stray infrared laser light did not affect optical tracking
      accuracy. The mean target registration errors while optically tracking the laser
      handpiece with a passive tip and the laser beam focus were 1.31+/-0.50 mm and
      2.31+/-0.92 mm, respectively, and were equivalent to the errors tracking a 24
      IRED pen probe from Northern Digital in a side-by-side comparison. The majority
      of error during ablation tracking derived from registration accuracy between
      physical space and the defined space of the ablation phantom and from an
      inability to freehand align the laser focus with the target in a consistent
      manner. While their magnitudes depend on spatial details of the tracking setup
      (e.g., number and distribution of fiducial points, working distance from the
      camera, etc.), these errors are inherent to any freehand laser surgery.

PMID- 15719973
TI  - Theoretical signal-to-noise ratio and spatial resolution dependence on the
      magnetic field strength for hyperpolarized noble gas magnetic resonance imaging
      of human lungs.
AB  - In hyperpolarized noble gas (HNG) magnetic resonance (MR) imaging, the available
      polarization is independent of magnetic field strength and for large
      radiofrequency (rf) coils, such as those used for chest imaging, the body noise
      becomes the primary noise source making signal-to-noise ratio (SNR) largely
      frequency independent at intermediate field strengths (0.1-0.5 T). Furthermore,
      the reduction in the transverse relaxation time, T2, of HNG in lungs with
      increasing field strength, results in a decrease in the achievable SNR at higher
      fields. In this work, the optimum field strength for HNG MR imaging was
      theoretically calculated in terms of both SNR and spatial resolution. SNR
      calculations used the principle of reciprocity and included contributions to the
      noise arising from both coil and sample losses in a chest-sized coil for lung
      imaging. The effects of susceptibility differences, transverse relaxation time,
      and diffusion were considered in the resolution calculations. The calculations
      show that the optimum field strength for HNG MR imaging of human lungs is between
      0.1 and 0.6 T depending on gas type (helium or xenon) and sample size. At the
      field strengths currently used by conventional clinical proton MR imaging systems
      (1-3 T), the predicted SNR are 10%-50% lower than at the optimum field with only
      slightly worse spatial resolution (10%-20%). At higher fields (>3 T), however,
      the SNR degrades considerably reducing the achievable spatial resolution.
      Although HNG of the lung is still feasible at very low field strengths (<50 mT),
      the available SNR is much lower than at optimum fields and this reduces the
      achievable spatial resolution. These findings suggest that HNG imaging may be
      optimally performed at much lower field strengths (0.1-0.6 T) than conventional
      clinical proton MR imaging systems. This could considerably decrease cost,
      improve patient access, and reduce chemical shift and susceptibility artifacts
      and rf heating.

PMID- 15719974
TI  - SURLAS: a new clinical grade ultrasound system for sequential or concomitant
      thermoradiotherapy of superficial tumors: applicator description.
AB  - A new ultrasound applicator with three-dimensional power distribution control was
      developed for simultaneous thermoradiotherapy. The system was named SURLAS for
      Scanning Ultrasound Reflector Linear Arrays System. In this paper, the hardware
      of the first clinical grade SURLAS applicator is described with emphasis on
      clinically important static acoustic characteristics and on construction aspects
      not reported before. Functionally, the SURLAS applicator consists of two parallel
      opposed ultrasound linear arrays aiming their acoustic beams to a V-shape
      scanning ultrasound reflector, which deflects the beams coming from opposite
      directions toward the treatment area. The reciprocating motion of the reflector
      in-between the arrays spreads the ultrasonic energy over the target area scanned.
      Control of power deposition over the 16 cm by 16 cm treatment window area is
      achieved by adjusting the power input into the transducer elements of the arrays
      as a function of the position of the scanning reflector. Furthermore, the arrays
      operate at significantly different frequencies (1.9 and 4.9 MHz) so that
      intensity modulation of beams of different frequencies can be exploited to adjust
      the depth of energy penetration. With this design, external electron or photon
      beams can be concurrently delivered with hyperthermia by irradiating through the
      applicator's body. Safety features were implemented into the applicator's design
      to monitor its performance during operation. A detailed description of the
      applicator including impedance matching circuits/filters, radiation force balance
      power measurements, hydrophone pressure field distribution measurements, as well
      as safety test results are reported.

PMID- 15719975
TI  - Volume CT with a flat-panel detector on a mobile, isocentric C-arm: pre-clinical
      investigation in guidance of minimally invasive surgery.
AB  - A mobile isocentric C-arm (Siemens PowerMobil) has been modified in our
      laboratory to include a large area flat-panel detector (in place of the x-ray
      image intensifier), providing multi-mode fluoroscopy and cone-beam computed
      tomography (CT) imaging capability. This platform represents a promising
      technology for minimally invasive, image-guided surgical procedures where
      precision in the placement of interventional tools with respect to bony and soft
      tissue structures is critical. The image quality and performance in surgical
      guidance was investigated in pre-clinical evaluation in image-guided spinal
      surgery. The control, acquisition, and reconstruction system are described. The
      reproducibility of geometric calibration, essential to achieving high three
      dimensional (3D) image quality, is tested over extended time scales (7 months)
      and across a broad range in C-arm angulation (up to 45 degrees), quantifying the
      effect of improper calibration on spatial resolution, soft-tissue visibility, and
      image artifacts. Phantom studies were performed to investigate the precision of
      3D localization (viz., fiber optic probes within a vertebral body) and effect of
      lateral projection truncation (limited field of view) on soft-tissue
      detectability in image reconstructions. Pre-clinical investigation was undertaken
      in a specific spinal procedure (photodynamic therapy of spinal metastases) in
      five animal subjects (pigs). In each procedure, placement of fiber optic
      catheters in two vertebrae (L1 and L2) was guided by fluoroscopy and cone-beam
      CT. Experience across five procedures is reported, focusing on 3D image quality,
      the effects of respiratory motion, limited field of view, reconstruction filter,
      and imaging dose. Overall, the intraoperative cone-beam CT images were sufficient
      for guidance of needles and catheters with respect to bony anatomy and improved
      surgical performance and confidence through 3D visualization and verification of
      transpedicular trajectories and tool placement. Future investigation includes
      improvement in image quality, particularly regarding x-ray scatter, motion
      artifacts and field of view, and integration with optical tracking and navigation
      systems.

PMID- 15719977
TI  - The American Board of Radiology Maintenance of Certification (MOC) Program in
      Radiologic Physics.
AB  - Maintenance of Certification (MOC) recognizes that in addition to medical
      knowledge, several essential elements involved in delivering quality care must be
      developed and maintained throughout one's career. The MOC process is designed to
      facilitate and document the professional development of each diplomate of The
      American Board of Radiology (ABR) through its focus on the essential elements of
      quality care in Diagnostic Radiology and its subspecialties, and in the
      specialties of Radiation Oncology and Radiologic Physics. The initial elements of
      the ABR-MOC have been developed in accord with guidelines of The American Board
      of Medical Specialties. All diplomates with a ten-year, time-limited primary
      certificate in Diagnostic Radiologic Physics, Therapeutic Radiologic Physics, or
      Medical Nuclear Physics who wish to maintain certification must successfully
      complete the requirements of the appropriate ABR-MOC program for their specialty.
      Holders of multiple certificates must meet ABR-MOC requirements specific to the
      certificates held. Diplomates with lifelong certificates are not required to
      participate in the MOC, but are strongly encouraged to do so. MOC is based on
      documentation of individual participation in the four components of MOC: (1)
      professional standing, (2) lifelong learning and self-assessment, (3) cognitive
      expertise, and (4) performance in practice. Within these components, MOC
      addresses six competencies: medical knowledge, patient care, interpersonal and
      communication skills, professionalism, practice-based learning and improvement,
      and systems-based practice.

PMID- 15719976
TI  - Rest period duration of the coronary arteries: implications for magnetic
      resonance coronary angiography.
AB  - Magnetic resonance (MR) and computed tomography coronary imaging is susceptible
      to artifacts caused by motion of the heart. The presence of rest periods during
      the cardiac and respiratory cycles suggests that images free of motion artifacts
      could be acquired. In this paper, we studied the rest period (RP) duration of the
      coronary arteries during a cardiac contraction and a tidal respiratory cycle. We
      also studied whether three MR motion correction methods could be used to increase
      the respiratory RP duration. Free breathing x-ray coronary angiograms were
      acquired in ten patients. The three-dimensional (3D) structure of the coronary
      arteries was reconstructed from a biplane acquisition using stereo reconstruction
      methods. The 3D motion of the arterial model was then recovered using an
      automatic motion tracking algorithm. The motion field was then decomposed into
      separate cardiac and respiratory components using a cardiac respiratory
      parametric model. For the proximal-to-middle segments of the right coronary
      artery (RCA), a cardiac RP (<1 mm 3D displacement) of 76+/-34 ms was measured at
      end systole (ES), and 65+/-42 ms in mid-diastole (MD). The cardiac RP was 80+/-25
      ms at ES and 112+/-42 ms at MD for the proximal 5 cm of the left coronary tree.
      At end expiration, the respiratory RP (in percent of the respiratory period) was
      26+/-8% for the RCA and 27+/-17% for the left coronary tree. Left coronary
      respiratory RP (<0.5 mm 3D displacement) increased with translation (32% of the
      respiratory period), rigid body (51%), and affine (79%) motion correction. The
      RCA respiratory RP using translational (27%) and rigid body (33%) motion
      correction were not statistically different from each other. Measurements of the
      cardiac and respiratory rest periods will improve our understanding of the
      temporal and spatial resolution constraints for coronary imaging.

PMID- 15719978
TI  - Dose perturbation of a novel cobalt chromium coronary stent on 32P intravascular
      brachytherapy: a monte carlo study.
AB  - Intravascular brachytherapy has been adopted for the indication of in-stent
      restenosis on the basis of results of clinical trials using mainly stainless
      steel stents. Recently, a new stent made of cobalt-chromium L-605 alloy (CoCr,
      p=9.22 g/cm3) (MULTI-LINK VISION) was introduced as an alternative to the 316L
      stainless steel stent design (SS, p=7.87 g/cm3) (MULTI-LINK PENTA). In this work,
      we used the Monte Carlo code MCNPX to compare the dose distribution for the 32P
      GALILEO source in CoCr and SS 8 mm stent models. The dose perturbation factor
      (DPF), defined as the ratio of the dose in water with the presence of a stent to
      the dose without a stent, was used to compare results. Both stent designs were
      virtually expanded to diameters of 2.0, 3.0, and 4.0 mm using finite element
      models. The complicated strut shapes of both the CoCr and SS stents were
      simplified using circular rings with an effective width to yield a metal-to
      tissue ratio identical to that of the actual stents. The mean DPF at a 1 mm
      tissue depth, over the entire stented length of 8 mm, was 0.935 for the CoCr
      stent and 0.911 for the SS stent. The mean DPF at the intima (0.05 mm radial
      distance from the strut outer surface), over the entire stented length of 8 mm,
      was 0.950 for CoCr, and 0.926 for SS. The maximum DPFs directly behind the CoCr
      and SS struts were 0.689 and 0.644, respectively. All DPF estimates have a
      standard deviation of +/-0.6%(k=2), approximating the 95% confidence interval.
      Although the CoCr stent has a higher effective atomic number and greater density
      than the SS stent, the DPFs for the two stents are similar, probably because the
      metal-to-tissue ratio and strut thickness of the CoCr stent are lower than those
      of the SS stent.

PMID- 15719979
TI  - DMLC leaf-pair optimal control for mobile, deforming target.
AB  - Existing algorithms of dynamic control of independent pairs of leaves allow
      optimal DMLC delivery of IMRT to rigid targets translating parallel to leaf
      trajectories. However, in numerous cases of radiotherapy treatments simplifying
      assumptions of rigid-like motions of targets and surrounding tissues are clearly
      not satisfied. Therefore algorithms have to be developed that allow one to
      control MLC so that predetermined intensities are delivered to various points in
      targets that experience compression and expansion at the time of irradiation.
      Moreover, it is desirable for such algorithms to ensure that delivery of
      modulated intensity map will be done with minimal expense of monitor units.
      Derivation of the algorithm that optimizes the DMLC IMRT to mobile, deforming
      target is presented in this paper. [To illustrate the general algorithm two
      representative examples of DMLC IMRT delivery to deforming targets are presented
      in full detail.] Finally, similarities and differences between solutions for
      immobile targets, for moving, rigid targets and for moving, deforming targets are
      discussed.

PMID- 15719980
TI  - Validation of Monte Carlo calculated surface doses for megavoltage photon beams.
AB  - Recent work has shown that there is significant uncertainty in measuring build-up
      doses in mega-voltage photon beams especially at high energies. In this present
      investigation we used a phantom-embedded extrapolation chamber (PEEC) made of
      Solid Water to validate Monte Carlo (MC)-calculated doses in the dose build-up
      region for 6 and 18 MV x-ray beams. The study showed that the percentage depth
      ionizations (PDIs) obtained from measurements are higher than the percentage
      depth doses (PDDs) obtained with Monte Carlo techniques. To validate the MC
      calculated PDDs, the design of the PEEC was incorporated into the simulations.
      While the MC-calculated and measured PDIs in the dose build-up region agree with
      one another for the 6 MV beam, a non-negligible difference is observed for the 18
      MV x-ray beam. A number of experiments and theoretical studies of various
      possible effects that could be the source of this discrepancy were performed. The
      contribution of contaminating neutrons and protons to the build-up dose region in
      the 18 MV x-ray beam is negligible. Moreover, the MC calculations using the XCOM
      photon cross-section database and the NIST bremsstrahlung differential cross
      section do not explain the discrepancy between the MC calculations and
      measurement in the dose build-up region for the 18 MV. A simple incorporation of
      triplet production events into the MC dose calculation increases the calculated
      doses in the build-up region but does not fully account for the discrepancy
      between measurement and calculations for the 18 MV x-ray beam.

PMID- 15719981
TI  - Comment on "Tomosynthesis-based localization of radioactive seeds in prostate
      brachytherapy" [Med. Phys. 30, 3135-3142 (2003)].

PMID- 15719982
TI  - The ecetoc approach to targeted environmental risk assessment.

PMID- 15719983
TI  - Toxicity assessment of mono-substituted benzenes and phenols using a Pseudomonas
      initial oxygen uptake assay.
AB  - A methodology is presented for assessing the toxicity of chemical substances
      through their inhibitory action toward the Pseudomonas initial oxygen uptake
      (PIOU) rate. The current studies reveal that the PIOU assay is rapid, cost
      efficient, and easy to perform. The oxygen uptake rate was found to be associated
      with a putative benzoate transporter and highly dependent on benzoate
      concentration. The putative benzoate transporter has been shown to follow
      Michaelis-Menten kinetics. Most phenols were found to be noncompetitive
      inhibitors of the benzoate transporter. The inhibition constant (Ki) of these
      noncompetitive inhibitors can be related to the concentration causing 50% oxygen
      uptake inhibition in Pseudomonas putida. Modeling these data by using the
      response-surface approach leads to the development of a quantitative structure
      activity relationship (QSAR) for the toxicity of phenols ((1/Ki) = -0.435 (+/
      0.038) lowest-unoccupied-molecular orbital + 0.517 (+/-0.027)log K(OW) - 2.340
      (+/-0.068), n = 49, r2 = 0.930, s = 0.107, r2adj = 0.926, F = 303.1). A
      comparison of QSAR models derived from the Ki data of the PIOU method and the
      toxicity data of 40-h Tetrahymena pyrifomis growth inhibition assay (Tetratox)
      indicated that there was a high correlation between the two approaches (r2 =
      0.925).

PMID- 15719984
TI  - Occurrence of twenty-six endocrine-disrupting compounds in environmental water
      samples from Catalonia, Spain.
AB  - We monitored 26 compounds known or suspected to be endocrine disruptors in
      several environmental water samples from a river, the sea, and an irrigation
      canal. Because of the various chemical properties of the compounds monitored,
      analyses were carried out by using two different methods. One method is based on
      solid-phase extraction (SPE) on-line coupled to gas chromatography-mass
      spectrometry through an on-column interface. Another is based on high-performance
      liquid chromatography-(electrospray) mass spectrometry working in negative
      ionization mode and using off-line SPE. The limits of detection for the two
      methods were at levels of low microg/L. Phthalates and bis-(2-ethylhexyl) adipate
      were found at levels between 0.05 and 13 microg/L in all of the water samples
      analyzed. Some pesticides, alkylphenols, and estrogens were determined in a few
      samples at levels below 0.1 microg/L.

PMID- 15719985
TI  - Polycyclic aromatic hydrocarbon behavior in bioactive soil slurry reactors
      amended with a nonionic surfactant.
AB  - The effects of an ethoxylated sorbitan fatty ester nonionic surfactant (Tween 80)
      on the bioavailability of polycyclic aromatic hydrocarbons (PAHs) were examined
      by using soil-free and dense-slurry (67% solids content, by wt) systems
      containing a creosote-contaminated field soil. The dispersed-micelle-phase PAHs
      in soil-free systems were not readily bioavailable to the mixed consortium of
      microbes indigenous to the creosote-contaminated soil. Instead, the microbes
      partially and preferentially utilized readily available portions of the
      surfactant as carbon sources (16-18% of the initial surfactant dose). This
      selective microbial attack resulted in destabilization of dispersed-phase
      micelles and significant decreases in molar solubilization ratio and micelle
      water partition coefficient values. Remarkably high dosages (>20 g/L) of Tween 80
      were required to enhance mobilization of the sorbed PAHs via micelle association
      because of the sorption of Tween 80 to the soil employed. The PAHs released from
      the destabilized micelles in soil-slurry systems either associated with sorbed
      phase surfactants or readsorbed to soil organic matter too rapidly to be
      biologically accessed, even by the acclimated PAH-degrading microbes present. The
      work provides important new information and practical insights to surfactant
      solubilization and mobilization technology applications for the bioremediation of
      PAH-contaminated soils and sediments.

PMID- 15719986
TI  - Quantitative identification of sources of dioxin-like polychlorinated biphenyls
      in sediments by a factor analysis model and a chemical mass balance model
      combined with Monte Carlo techniques.
AB  - The major sources of dioxin-like polychlorinated biphenyls (PCBs) in two sediment
      cores from Tokyo Bay and Lake Shinji (both in Japan) were identified and their
      source contributions estimated using two receptor models. The first was a
      nonnegative constrained factor analysis (FA) model, and the second was a
      nonnegative constrained chemical mass balance model combined with Monte Carlo
      techniques (CMB-MC) to take into account the variability and uncertainty in both
      PCB congener profiles of sources and environmental samples. According to the FA
      model, variations in the concentrations of dioxin-like PCBs in each sediment core
      were accounted for almost entirely by two factors, which were considered to
      correspond to Kanechlors (KCs; Japanese PCB products) and incineration. The CMB
      MC model investigated the trends of the burdens from four types of KCs and
      incineration to the concentrations of dioxin-like PCBs in each sediment core. The
      results for both sediment cores obtained by both models indicated that the burden
      from KCs increased gradually beginning in the 1950s, peaked around 1970, and
      declined thereafter, whereas the burden from incineration increased gradually
      from the 1950s to the early 1990s. The estimated contribution from incineration
      to the toxic equivalent concentration of dioxin-like PCBs was comparable to that
      from KCs.

PMID- 15719987
TI  - Impact of imposed anaerobic conditions and microbial activity on aqueous-phase
      solubility of polycyclic aromatic hydrocarbons from soil.
AB  - The influence of anaerobic conditions on aqueous-phase polycyclic aromatic
      hydrocarbon (PAH) bioavailability was investigated in laboratory microcosms.
      Highly aged (>70 years), PAH-contaminated soil was incubated under anaerobic
      conditions by using various anaerobic headspaces, anaerobic headspaces with an
      oxygen-scavenging complex (titanium(III) citrate) in the aqueous phase, or
      anaerobic headspaces with electron-acceptor amendments in the aqueous phase.
      Incubation of soil solely under anaerobic conditions resulted in increased
      aqueous concentrations of all PAHs tested (fluoranthene, pyrene,
      benz[a]anthracene, and benzo[a]pyrene). Benz[a]anthracene and benzo[a]pyrene
      extractable concentrations were above aqueous solubility, by as much as an order
      of magnitude for the latter. The degree of solubility increase observed was a
      function of molecular weight of the PAH regardless of initial soil concentration,
      suggesting formation of stable PAH-soluble organic matter associations. The soil
      samples incubated aerobically for 90 d before imposition of anaerobic conditions
      did not release PAHs to the aqueous phase. Methanogenic organisms and sulfate
      reducing bacteria were seen to have the most significant effect on increases in
      aqueous-phase PAHs. Polycyclic aromatic hydrocarbons made more soluble under
      anaerobic conditions was available to be degraded or transformed under aerobic
      conditions.

PMID- 15719988
TI  - Relationships between Cd and Zn partitioning and geochemical composition in
      sediments from Chinese rivers.
AB  - Adsorption isotherm experiments were conducted to determine the distribution
      coefficients (Kd) for Cd and Zn between water and sediments from twelve rivers in
      eastern China. The low metal concentration (<10(-10) M) added into the sediment
      water system enabled the direct measurements of linear adsorption isotherms. When
      other solution parameters, such as ionic strength, were controlled, sediment
      geochemical characteristics were the major factors affecting metal distribution.
      The Kd was highly dependent on the total organic carbon contents and Fe-Mn oxide
      at pH = 7.0, and was affected significantly by the carbonate content in the
      sediments due to its control of pH. The Kd of the Huanghe sediments, which had
      the highest carbonate concentration (13.1%), increased sharply for both Cd and Zn
      when the pH increased. A quantitative model using the experimentally obtained
      phase distribution coefficients (Kd)i was applied to study the effects of
      different geochemical phases in the sediment on metal distributions. The (Kd)i of
      carbonate was correlated significantly with the carbonate content in the
      sediment, whereas the (Kd)i of total organic carbon (TOC) and Fe-Mn oxide phases
      were highly pH dependent. Using the (Kd)i for each geochemical phase, the
      calculation showed that about 91% and 85% of sorbed Cd and Zn, respectively,
      added to the batch reactors were distributed among the three major geochemical
      phases: TOC, Fe-Mn oxide, and carbonate. Total organic carbon was the most
      important binding phase for Cd, and Fe-Mn oxide for Zn. Furthermore, adsorption
      experiments with simulated sediments show the importance of interactions between
      different geochemical phases on metal partitioning.

PMID- 15719989
TI  - Predicting and observing responses of algal communities to photosystem II
      herbicide exposure using pollution-induced community tolerance and species
      sensitivity distributions.
AB  - Various test strategies are in use in ecotoxicology to assess the potential risks
      of toxicants on aquatic communities. The species-sensitivity distribution concept
      (SSD) works by arranging single-species laboratory test data in a cumulative
      frequency distribution. The pollution-induced community tolerance concept (PICT)
      uses observable community responses by measuring increases in community tolerance
      caused by the replacement of sensitive species after exposure. The aim of this
      study was to compare these two concepts in assessing the effects of three
      herbicides. Atrazine, prometryn, and isoproturon were found to increase community
      tolerance by a factor up to six. Atrazine increased community tolerance only at
      higher test concentrations (0.125 mg L(-1)). Species-sensitivity distributions
      correspond well to community responses: The median effective concentrations
      (EC50s) of untreated periphyton communities tested covered 55 to 65% of affected
      species represented in the SSD. The sensitivities of tolerant algal communities
      shifted to the right end of the SSDs. In the microcosm experiments, higher test
      concentrations affected biomass, species numbers, and community structure.
      Community tolerance could not be induced any further, suggesting that these
      concentrations represent a maximum of functional redundancy of a functional
      group. At higher concentrations, even the least-sensitive species are affected.
      These results can be interpreted as a confirmation of the SSD concept by observed
      algal community responses, when applied to photosystem II (PSII)-inhibiting
      herbicides.

PMID- 15719991
TI  - Whole-carcass residues of the rodenticide difenacoum in anticoagulant-resistant
      and -susceptible rat strains (Rattus norvegicus).
AB  - The present study investigated the whole-carcass residue carried by resistant and
      susceptible laboratory rat strains following 5, 10, or 20 d of feeding on a diet
      of 25 mg difenacoum/kg bait. The mean whole-carcass residue of difenacoum was
      determined by high-performance liquid chromatography to be between 0.52 and 0.74
      mg/kg body weight in all three rat strains tested. These values were considerably
      lower than some comparable data previously reported for other species and second
      generation rodenticides as well as from mathematical models. The whole-carcass
      residue of extractable (i.e., nonrefractory) parent compound carried by highly
      resistant rats fed for 20 d (0.74 mg/kg body wt) is unlikely to present a
      significantly increased risk to predators compared to the amount carried by
      susceptible rats after 5 d of feeding (0.52 mg/kg body wt). However, resistant
      rats are more likely to be available for predation and to be carrying a whole
      carcass residue of anticoagulant throughout the duration of a control program.

PMID- 15719990
TI  - Black-bellied whistling duck (Dendrocygna autumnalis) brain cholinesterase
      characterization and diagnosis of anticholinesterase pesticide exposure in wild
      populations from Mexico.
AB  - Rice is the main crop in the subbasin of the fluvial lagoon system of Palizada
      River (FLSPR) in the state of Campeche, Mexico. The pesticides used to control
      pests of this crop mainly are carbofuran, chlorpyrifos, and glyphosate. Black
      bellied whistling duck (Dendrocygna autumnalis) is an ecologically and
      economically important species in the area. This duck is consumed by local
      inhabitants throughout the year, despite its potential exposure to pesticides.
      Due to its feeding habits, abundance, and nutritional value, D. autumnalis is a
      good indicator of environmental contamination and a potential route of human
      exposure to organophosphate and carbamate pesticides. In this study, the brain
      cholinesterase (ChE) in the frontal cerebral cortex of autochthonous ducks was
      characterized. In addition, the potential of the three locally used pesticides
      and mixtures to inhibit ChE activity was investigated and the exposure of the
      wild duck population during intensive pesticide applications in rice fields was
      evaluated. We found that acetylcholinesterase (AChE) seems to be the predominant
      ChE form in the biological fraction analyzed. Carbofuran was the most potent ChE
      inhibitor of D. autumnalis brain ChE activity from the three pesticides analyzed.
      Cholinesterase inhibition after exposure to pesticide mixtures predominantly was
      due to carbofuran. A decrease (p < 0.05) in AChE activity (>30%) was apparent in
      wild ducks compared to reference ducks, with recovery of ChE inhibition in wild
      ducks occurring months later when no pesticides were applied in the field.
      Dendrocygna autumnalis brain ChE is a suitable parameter for inclusion in
      biomonitoring programs for both environmental protection and human safety.

PMID- 15719992
TI  - Algal toxicity of nitrobenzenes: combined effect analysis as a pharmacological
      probe for similar modes of interaction.
AB  - An analysis regarding the effects of the mixture toxicity of different
      nitrobenzenes on the reproduction of the green alga Scenedesmus vacuolatus was
      undertaken using the concepts of concentration addition and response addition.
      Using lipophilicity-based quantitative structure-activity relationship (QSAR)
      modeling for nitrobenzenes, the assumption is held that mononitrobenzenes may
      exert narcotic effects as a common type of action, whereas dinitrobenzenes show a
      somewhat greater toxicity. From the literature, QSARs based on quantum chemical
      parameters suggest that some mononitrobenzenes may be effective through
      additional other modes of action. The toxicity of a mixture of 14 nitrobenzenes
      clearly exceeds the predicted combined effects, as expected for the sum of toxic
      units from a uniform narcotic mode of action. Moreover, the observed combined
      effect is smaller than that predicted from similarly acting compounds calculated
      on the basis of the parameterized dose-response functions using concentration
      addition. Further modeling of the combined effect, joining the models of
      concentration addition for components with anticipated similar modes of action
      and of response addition for those with independent action, led us to propose
      that not all nitrobenzenes follow the same mode of action. This idea is in line
      with the hypothesis derived from quantum chemical QSAR considerations. Most
      interestingly, the methodology introduced here uses combined effect analysis as a
      pharmacological probe to test for similarity in the mode of action of mixture
      components.

PMID- 15719993
TI  - Hormetic effects of gamma radiation on the stress axis of natural populations of
      meadow voles (Microtus pennsylvanicus).
AB  - We tested the hypothesis that low doses of gamma radiation have beneficial,
      hormetic effects on the stress axis (the hypothalamic-pituitary-adrenocortical
      axis) of free-ranging meadow vole populations (Microtus pennsylvanicus). Voles
      were exposed to chronic gamma radiation from a 137Cs field irradiator. In
      isolated populations, voles received one of three treatments over a four-year
      period: Controls (0.19-0.42 microGy/h--levels that were 2-5x above background
      levels [0.1 microGy/h] and live-trapped in all years--1982--1985), low doses
      (22.6 microGy/h--50-200x background, live-trapped from November 1982--April
      1985), or high doses (3,840 microGy/h--40,000x background, live-trapped from
      November 1983--April 1985). Voles exposed to a low dose had levels of free and
      total corticosterone that were significantly higher than those in the control or
      high-dose groups. Differences in response to radiation between the sexes were
      apparent for maximum corticosterone-binding capacity, with females exposed to low
      doses having higher binding capacity than control or high-dose females, whereas
      males exposed to low doses had lower binding capacity than control or high-dose
      males. Low-dose voles had higher counts of neutrophils than either the controls
      or high-dose voles; hematocrit was greater in the controls than in irradiated
      voles. These results indicate that voles display a hormetic response to
      radiation, wherein low doses of an otherwise harmful agent produce a beneficial
      effect. The stimulation of the stress axis resulting in the increased secretion
      of glucocorticoids, which may protect against the excessive actions of the immune
      and inflammatory responses, may be a key mechanism producing this effect.

PMID- 15719994
TI  - Functional relationships among selenium concentrations in the diet, target
      tissues, and nondestructive tissue samples of two species of snakes.
AB  - Nondestructive sampling methods, such as removal of feathers for contaminant
      analysis, are desirable in ecological monitoring programs that seek to minimize
      the impacts of harvesting organisms. Although many reptiles are declining
      worldwide, nondestructive sampling techniques seldom have been employed for
      assessing contaminant exposure in these organisms. In this study, we examined the
      utility of nondestructive tissue sampling for assessing Se exposure in reptiles.
      We describe the functional relationships among dietary Se concentrations, target
      tissue Se concentrations, and Se concentrations in nondestructive tissue samples
      (blood and tail tissue biopsy) in two species of snakes that had been exposed to
      Se under very different experimental protocols. Using nonlinear regression, we
      found strong positive correlations (r2 > 0.92) in all comparisons among Se
      concentrations in nondestructive tissues, diet, and target tissues. Moreover,
      equations describing these relationships can be used to estimate concentrations
      of Se in diet and target organs, from known concentrations of Se in
      nondestructive tissue samples. Although the current paucity of toxicity data on
      reptiles precludes tests of our models, we demonstrate how the equations
      describing these relationships might be used to make predictions about Se
      accumulation in target organs for risk assessment. Future studies on reptiles
      that examine these relationships under different Se exposure conditions, and
      those that document physiological responses of reptiles to various concentrations
      of Se, will help to refine our models and test their efficacy for predicting
      health risk.

PMID- 15719996
TI  - Analysis of a database of pesticide residues on plants for wildlife risk
      assessment.
AB  - Current methods to estimate exposure of wildlife to pesticides from diet depend
      on a database of published residue concentrations on crop plants normalized to a
      standard application rate to obtain a residue from a unit dosage (RUD). This
      database, first published in the early 1970s, was updated in the 1990s. For each
      category of crops, maximum and mean residues are determined and used to
      extrapolate concentrations on plants across application rates in calculations of
      risk. The present study aims to update the database, to examine the validity of
      extrapolating RUD values across application rates, and to improve the
      categorization of crops using crop morphology and cultivation methods. The slope
      of the linear regression of residue concentrations against application rate in 41
      trials was significantly different from one in all but five cases. This supports
      the assumption that residue concentrations are directly proportional to the
      application rate, although less than half the variance in residue concentrations
      was explained by the linear model. Residues on leaves were partitioned into eight
      categories of crops using information regarding plant morphology and cultivation
      method. Fruit size was an additional variable useful for segregating residues
      into four categories: Small fruits, large fruits, pods, and grains. The proposed
      changes increase the amount of variance explained in the residue database from 19
      to 32%. Depending on the crop category, residues on fruits were 2- to 16-fold
      lower than those on leaves. Residue concentrations on leaves of short plants were
      more than fourfold higher than those on leaves of tall plants. Descriptive
      statistics are provided for each of the proposed crop categories.

PMID- 15719995
TI  - Relationship between ethinylestradiol-mediated changes in endocrine function and
      reproductive impairment in Japanese medaka (Oryzias latipes).
AB  - Many biochemical endpoints currently are used to describe endocrine function in
      fish; however, the sensitivity of these parameters as biomarkers of impaired
      reproduction or sexual development is not well understood. In the present study,
      adult Japanese medaka (Oryzias latipes) were assessed for reproductive output and
      endocrine function, including circulating steroid concentrations, ex vivo
      steroidogenesis from the gonads, aromatase activity, hepatic estrogen receptor
      (ER), and plasma vitellogenin (VTG) after exposure to 0, 0.2, 5, 500, and 2,000
      ng/L of 17alpha-ethinylestradiol (EE) for 14 d. The EE altered these biochemical
      responses at various sites along the hypothalamus-pituitary-gonadal axis at
      concentrations as low as 0.2 ng/L, but it only depressed reproductive function at
      concentrations of 500 ng/L or greater. Offspring also had reduced ability to
      hatch at 500 ng/L of EE, but this concentration did not produce any other
      observed changes in development or sexual phenotype. The reproductive parameters
      correlated well with VTG, ER, and gonadosomatic index (GSI) in both sexes of
      adult medaka, which could be indicative of the ER-mediated mode of action for EE.
      Vitellogenin and ER were elevated at higher concentrations of EE in both sexes,
      whereas GSI was decreased. Overall, most biochemical endpoints were more
      sensitive than reproduction or development to exposure, indicating that
      reproductive function may be relatively protected.

PMID- 15719997
TI  - Effect of toxic cations on copper rhizotoxicity in wheat seedlings.
AB  - Copper pollution may occur in acidic soils where the low pH leads to release of
      Al and Mn in soil solution, which could interact with Cu toxicity. Very little
      information exists regarding the influence of toxic cations on the phytotoxicity
      of Cu. In this study, we tested the hypothesis that phytotoxicity of Cu2+ may be
      overestimated in acidic soils due to synergism between Al or Mn and Cu toxicity.
      Rhizotoxicity of Al, Mn, and Cu to wheat seedlings was studied in well-defined
      nutrient solutions, with these elements present singly or in combination.
      Toxicity was expressed on a solution metal-activity basis, with metal activities
      calculated using GEOCHEM-PC and verified using Donnan dialysis. Of the three
      ions, Cu2+ was the most rhizotoxic, with activities of Cu2+, Al3+, and Mn2+
      resulting in a 25% reduction in root elongation of 0.12, 1.26, and 211 microM,
      respectively. Although there was no interaction between Mn2+ and Cu2+ toxicity,
      Cu2+ was significantly less toxic on a relative basis in the presence of Al3+.
      Thus, critical thresholds for soil solution Cu2+ activity determined in acidic
      soils will be underprotective compared to soils that contain low concentrations
      of soluble Al (e.g., limed or nonacidic soils).

PMID- 15719998
TI  - Insecticide species sensitivity distributions: importance of test species
      selection and relevance to aquatic ecosystems.
AB  - Single-species acute toxicity data and (micro)mesocosm data were collated for 16
      insecticides. These data were used to investigate the importance of test-species
      selection in constructing species sensitivity distributions (SSDs) and the
      ability of estimated hazardous concentrations (HCs) to protect freshwater aquatic
      ecosystems. A log-normal model was fitted to a minimum of six data points, and
      the resulting distribution was used to estimate lower (95% confidence), median
      (50% confidence), and upper (5% confidence) 5% HC (HC5) values. Species
      sensitivity distributions for specific taxonomic groups (vertebrates, arthropods,
      nonarthropod invertebrates), habitats (saltwater, freshwater, lentic, lotic), and
      geographical regions (Palaearctic, Nearctic, temperate, tropical) were compared.
      The taxonomic composition of the species assemblage used to construct the SSD
      does have a significant influence on the assessment of hazard, but the habitat
      and geographical distribution of the species do not. Moreover, SSDs constructed
      using species recommended in test guidelines did not differ significantly from
      those constructed using nonrecommended species. Hazardous concentrations
      estimated using laboratory-derived acute toxicity data for freshwater arthropods
      (i.e., the most sensitive taxonomic group) were compared to the response of
      freshwater ecosystems exposed to insecticides. The sensitivity distributions of
      freshwater arthropods were similar for both field and laboratory exposure, and
      the lower HC5 (95% protection with 95% confidence) estimate was protective of
      adverse ecological effects in freshwater ecosystems. The corresponding median HC5
      (95% protection level with 50% confidence) was generally protective of single
      applications of insecticide but not of continuous or multiple applications. In
      the latter cases, a safety factor of at least five should be applied to the
      median HC5.

PMID- 15719999
TI  - Detection and evaluation of endocrine-disruption activity in water samples from
      Portuguese rivers.
AB  - Water samples (n = 183) from Portuguese rivers were tested for the presence of
      endocrine disruptors using the recombinant yeast assay (RYA) combined with
      chemical identification of compounds having endocrine-disruption properties by
      liquid chromatography coupled to mass spectrometry. Ten selected locations were
      sampled monthly for a period of 20 months, from April 2001 to December 2002. More
      than 90% of samples showed either no detectable or low levels of estrogenicity
      (<0.1 ng/L of estradiol equivalents). The remaining samples (17 in total, 9.3%)
      showed estrogenicity values ranging from 0.1 to 1.7 ng/L of estradiol
      equivalents; only two samples showed values greater than 1 ng/L of estradiol
      equivalents. Most highly estrogenic samples (13 of 17 samples) originated in five
      sampling sites clustered in two zones near Porto and Lisbon. Chemical analysis
      detected alkylphenolic compounds (octyl- and nonylphenol plus nonylphenol
      ethoxylates) in all samples, albeit at concentrations less than 1 microg/L for
      each compound in 80% of samples. Total analyte concentration exceeded 10 microg/L
      in only 10 samples, with all but one of those originating from only two sampling
      sites. In these two locations, a good correlation was observed between the
      concentrations of octylphenol, nonylphenol, and to a lesser extent, bisphenol A
      in the samples and their estrogenicity values as calculated by RYA. We conclude
      that estrogenic activity can be explained by alkylphenol contamination in only
      these sites; for the remainder, we propose that pesticides and urban waste may be
      the main factors responsible for estrogenic contamination.

PMID- 15720000
TI  - Bioconcentration and elimination of avermectin B1 in sturgeon.
AB  - The bioconcentration and elimination of avermectin B1 in sturgeon muscle were
      investigated with high-performance liquid chromatography. Mean concentrations of
      0.2 and 1 ng x ml(-1) in water were maintained for a 22-d exposure period. The
      concentrations of avermectin B1alpha in muscle tissues reached steady state
      within 14 to 18 d. The level of avermectin B1 concentrations in the fish muscles
      was 7.75+/-0.88 and 38.29+/-1.65 ng x g(-1) for the low and high concentrations,
      respectively, on day 22. The half-life (t1/2) of the concentrations for the two
      treated groups was 4.95 and 4.33 d for the low and high concentrations,
      respectively. Greater than 95% of the tissue concentrations were eliminated from
      the exposed fish after the 14- and 18-d elimination periods. The estimated values
      of the bioconcentration factor were 42 L/kg for the low-concentration group and
      41 L/kg for high-concentration group, and these values were not significantly
      different (alpha = 0.05). Avermectin B1alpha does not strongly bioconcentrate in
      individual aquatic organism and would not be expected to biomagnify in the food
      chain.

PMID- 15720001
TI  - Brominated flame retardants: activities in a crustacean development test and in
      an ecdysteroid screening assay.
AB  - Brominated flame retardants (BFRs) were investigated for toxic effects both in
      vivo and in vitro in two invertebrate bioassays. Subchronic effects of
      tetrabromobisphenol A (TBBPA), tribromophenol (TBP), and four polybrominated
      diphenyl ethers ([PBDEs]; BDE-28, BDE-47, BDE-99, and BDE-100) on larval
      development of the marine copepod Acartia tonsa were studied. For TBBPA and TBP 5
      d effective median concentration (EC50) values for inhibition of the larval
      development rate were 125 and 810 microg/L, respectively, whereas the PBDEs were
      much more potent with 5-d EC50 in the low microg/L range (1.2 microg/L for BDE
      100; 4.2 microg/L for BDE-99; 13 microg/L for BDE-28; and 13 microg/L for BDE
      47). These concentrations were up to two orders of magnitude below the 48-h LC50
      for acute adult toxicity (108 microg/L for BDE-28; 400 microg/L for TBBPA; 520
      microg/L for BDE-100; 705 microg/L for BDE-99; 1,500 microg/L for TBP; and 2,370
      microg/L for BDE-47). To distinguish between general toxicological and endocrine
      mediated toxic effects, the BFRs were assessed in vitro for ecdysteroid
      agonistic/antagonistic activity with the ecdysteroid-responsive Drosophila
      melanogaster B(II)-cell line. The pentabrominated diphenyl ethers BDE-99 and BDE
      100 showed weak ecdysteroid antagonistic activity. Thus, these PBDEs may be
      regarded as potential endocrine disrupters in invertebrates. The combination of
      in vitro assays and subchronic biotests with ecologically important crustacean
      species is a rapid and cost-effective tool when screening for sublethal effects
      of BFRs and other chemicals.

PMID- 15720002
TI  - Evaluation of acute copper toxicity to larval fathead minnows (Pimephales
      promelas) in soft surface waters.
AB  - The hardness-based regulatory approach for Cu prescribes an extrapolation of the
      toxicity-versus-hardness relationship to low hardness (< or =50 mg/L as CaCO3).
      Hence, the objective of the present research was to evaluate the influences of
      water quality on acute Cu toxicity to larval fathead minnow (Pimephales promelas)
      in low-hardness surface waters. Seasonal water sampling was conducted at 24 sites
      throughout South Carolina, USA, to determine the site-specific influences of soft
      surface-water conditions on acute Cu toxicity. Concurrent toxicity tests in
      laboratory water, matched for hardness and alkalinity (modified method), also
      were conducted to allow calculation of water-effect ratios (WERs). In addition,
      tests were conducted at recommended hardness levels (recommended method) for
      comparison of WER methodology in soft water. Surface-water conditions (average+/
      standard deviation, n = 53) were hardness of 16+/-8 mg/L as CaCO3, alkalinity of
      18+/-11 mg/L as CaCO3, and dissolved organic carbon of 6+/-4 mg/L. Dissolved Cu
      48-h median lethal concentration (LC50) values varied nearly 45-fold across the
      dataset and greater than four-fold at individual sites. Spatial (p < 0.0001) and
      seasonal (p = 0.026) differences among LC50 values were determined for eight
      sites that had multiple toxicity results for one year. All modified WERs were
      greater than 1.0, suggesting that the site waters were more protective of Cu
      toxicity than the matched laboratory water. Some WERs generated using recommended
      methods were less than 1.0, suggesting limited site-specific protection. Based on
      these observations, extrapolation of the hardness-based equation for Cu at 50
      mg/L or less as CaCO3 would adequately protect fathead minnow populations in soft
      surface waters. The WER results presented here demonstrate the inconsistency
      between hardness-based criteria and the methodology for deriving site-specific
      water-quality criteria in low-hardness waters.

PMID- 15720003
TI  - Use of laboratory toxicity tests with bivalve and echinoderm embryos to evaluate
      the bioavailability of copper in San Diego Bay, California, USA.
AB  - Copper concentrations in parts of San Diego Bay (CA, USA) exceed ambient water
      quality criteria (WQC; currently 3.1 microg/L dissolved, U.S. Environmental
      Protection Agency [U.S. EPA]). In order to better understand the bioavailability
      of copper to water-column organisms in the bay, toxicity tests were performed
      with copper added to surface water collected from various sites in the estuary
      over a three-year period. The species and endpoints used, bivalve and echinoderm
      embryo-larval development, are among the most sensitive in the U.S. EPA's
      national toxicity dataset, which is used to derive WQC. No toxicity was observed
      in ambient bay water samples, as indicated by high proportions of normally
      developed larvae in control treatments, averaging 93+/-5% across all sites and
      all sampling events. Median effects concentrations (EC50), obtained by copper
      spiking of ambient water samples, ranged from 1.7 to 3.4 times lower at sites
      located near the mouth compared to sites near the back of the bay. These data
      indicate a gradient in complexation capacity increasing from the mouth to the
      back of the bay, which is consistent with similar trends in dissolved organic
      carbon and total suspended solids. For the bay as a whole, estimates for total
      recoverable and dissolved water-effect ratios (WER) ranged from 2.07 to 2.27 and
      1.54 to 1.67, respectively. Water-effect ratios of this magnitude suggest that
      adoption of a somewhat higher site-specific WQC for San Diego Bay still would
      achieve the level of protection that is intended by the WQC guidelines.

PMID- 15720005
TI  - Behavioral responses to sublethal cadmium exposure within an experimental aquatic
      food web.
AB  - The foraging and predator-avoidance behaviors of mayfly (Baetis tricaudatus)
      nymphs and predator-prey interactions were investigated under differing
      combinations of cadmium concentration and predation risk. Predators consisted of
      stonefly (Kogotus nonus) nymphs, juvenile brook trout (Salvelinus fontinalis),
      and longnose dace (Rhinichthys cataractae), either alone or in combination.
      Organisms were exposed to 0, 0.5, or 5.0 microg/L Cd for 7 d (invertebrates) or
      30 d (vertebrates) prior to observation in artificial stream channels. Behavioral
      observations (20-min duration) were made both day and night over a 24-h period.
      Mayfly feeding rate was assessed by image analysis of grazed diatom mats cultured
      on ceramic tiles. Both predators and cadmium produced significant effects on the
      behavior of B. tricaudatus and K. nonus nymphs, with mayflies showing a
      hierarchical response in the presence of multiple predators. A significant
      increase in activity was observed in S. fontinalis exposed to 5.0 microg/L Cd,
      with significant decreases in capture efficiency of prey items apparent at 0.5
      microg/L Cd. Conversely, the foraging behavior of R. cataractae was unaffected by
      cadmium, possibly as a result of species-specific cadmium tolerance. Such
      sublethal effects of a contaminant on the energy budgets of individuals and the
      interactions between species have implications for community structure in aquatic
      food webs.

PMID- 15720004
TI  - Toxicity of fluoroquinolone antibiotics to aquatic organisms.
AB  - Toxicity tests were performed with seven fluoroquinolone antibiotics,
      ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, clinafloxacin,
      enrofloxacin, and flumequine, on five aquatic organisms. Overall toxicity values
      ranged from 7.9 to 23,000 microg/L. The cyanobacterium Microcystis aeruginosa was
      the most sensitive organism (5-d growth and reproduction, effective
      concentrations [EC50s] ranging from 7.9 to 1,960 microg/L and a median of 49
      microg/L), followed by duckweed (Lemna minor, 7-d reproduction, EC50 values
      ranged from 53 to 2,470 microg/L with a median of 106 microg/L) and the green
      alga Pseudokirchneriella subcapitata (3-d growth and reproduction, EC50 values
      ranged from 1,100 to 22,700 microg/L with a median 7,400 microg/L). Results from
      tests with the crustacean Daphnia magna (48-h survival) and fathead minnow
      (Pimephales promelas, 7-d early life stage survival and growth) showed limited
      toxicity with no-observed-effect concentrations at or near 10 mg/L. Fish dry
      weights obtained in the ciprofloxacin, levofloxacin, and ofloxacin treatments (10
      mg/L) were significantly higher than in control fish. The hazard of adverse
      effects occurring to the tested organisms in the environment was quantified by
      using hazard quotients. An estimated environmental concentration of 1 microg/L
      was chosen based on measured environmental concentrations previously reported in
      surface water; at this level, only M. aeruginosa may be at risk in surface water.
      However, the selective toxicity of these compounds may have implications for
      aquatic community structure.

PMID- 15720006
TI  - Feathers as a nondestructive biomonitor for persistent organic pollutants.
AB  - Keratinous tissues of mammals and humans, such as hair, have been used to
      determine the exposure to polychlorinated biphenyls (PCBs) and organochlorine
      pesticides. In the present study, we investigated the accumulation of persistent
      organic pollutants (POPs; PCBs, p,p'-DDT, p,p'-dichlorodiphenyldichloroethane
      [DDD], p,p'-dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB],
      oxychlordane, trans-nonachlor, polybrominated diphenyl ethers, and polybrominated
      biphenyls [PBBs]) in feathers of the great tit (Parus major). The accumulation of
      POPs in feathers and fat samples of 27 adult great tits collected in April 2000
      and December 2002 was compared with regard to possible temporal and spatial
      differences. Polybrominated diphenyl ethers, PBBs, trans-nonachlor, and HCB could
      not be quantified in feathers. Most PCB congeners and DDTs (p,p'-DDE, p,p'-DDD,
      and p,p'-DDT) could be determined in feathers, although concentrations in
      feathers were markedly lower (sigmaPCB concentration range, 28.2-87.1 ng/g) than
      concentrations in fat (sigmaPCB concentration range, 1244-10074 ng/g). Feathers
      had relatively higher levels of low-chlorinated PCBs (tetra- and pentachlorinated
      biphenyls) and p,p'-DDD compared to levels in fat, presumably reflecting levels
      in blood. Persistent organic pollutant concentrations did not increase with the
      age of the feather, suggesting that exogenous or aerial depositions of POPs onto
      the feather surface had no, or only minimal, influence on levels in feathers. For
      almost all compounds studied, POPs in feathers and fat were significantly
      positively correlated in samples collected during the breeding season but not in
      samples collected during the winter. This temporal difference may have been
      caused by seasonal changes in lipid reserves. Although further research is
      required, feathers appear to be a promising new, nondestructive biomonitor for
      PCBs and DDTs in avian wildlife.

PMID- 15720007
TI  - Hepatic porphyria induced by the herbicide tralkoxydim in small mammals is
      species-specific.
AB  - Tralkoxydim is the active ingredient in a postemergent herbicide used in cereal
      crops. During preregistration trials, tralkoxydim was observed to cause hepatic
      porphyria and cholestasis in laboratory mice. Porphyria was not seen in similarly
      exposed rats or hamsters, but data were not collected regarding the
      susceptibility of any wild small mammal species to the tralkoxydim-induced
      porphyria. To address this data gap, we exposed small mammals to tralkoxydim, to
      3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC; a known porphyrinogenic
      chemical), or to sunflower oil alone. We studied small mammal species that might
      be exposed following agricultural applications of the herbicide, including the
      white-footed mouse (Peromyscus leucopus), the deer mouse (P. maniculatus), and
      the meadow vole (Microtus pennsylvanicus). Because of their known susceptibility
      to both tralkoxydim- and DDC-induced porphyria, commercially supplied Mus
      musculus (CD-1 Swiss mice) were exposed as positive-control animals. We also
      exposed offspring of wild-caught M. musculus to compare their responses to those
      of the commercially supplied animals. Potential hepatotoxicity was determined by
      assessing the accumulation of liver protoporphyrin. Of the species tested, only
      M. musculus was susceptible to the porphyrinogenic action of tralkoxydim, and no
      significant accumulation of protoporphyrin was observed in any of the other
      species exposed to the herbicide.

PMID- 15720008
TI  - Impact of oil-sands based wetlands on the growth of mallard (Anas platyrhynchos)
      ducklings.
AB  - Identifying the potential effects of industrially formed wetlands on waterfowl
      populations is important for assessing the suitability of such wetlands in
      industrial reclamation strategies. Mallard ducklings were held in situ on two
      industrially formed wetlands and one reference wetland in northern Alberta,
      Canada. Duckling mass and skeletal size were measured at regular intervals over
      33 d, and blood was collected to investigate the analysis of plasma metabolites
      (triglyceride and glycerol) as an indicator of physiological condition. In
      repeated-measures analysis of variance (ANOVA), multivariate ANOVA, and
      subsequent multiple-comparisons tests, body mass and skeletal size were
      significantly lower in ducklings maintained on the industrial wetland after 2, 5,
      9, and 13 d of exposure. In this situation, plasma metabolite analysis did not
      provide additional information on mass-independent condition. We conclude that if
      the observed differences in growth and size translate into a decreased survival
      of juvenile waterfowl inhabiting these wetlands, then populations of these birds
      in the area could be negatively affected. We emphasize the importance of field
      based ecological research in toxicological studies of wildlife.

PMID- 15720009
TI  - Determination of select antidepressants in fish from an effluent-dominated
      stream.
AB  - Increasing evidence indicates widespread occurrence of pharmaceuticals and
      personal care products (PPCPs) in municipal effluent discharges and surface
      waters. Studies that characterize the fate and effects of PPCPs in aquatic
      systems are limited, and to our knowledge, data regarding pharmaceutical
      accumulation in fish of effluent-dominated ecosystems have not been previously
      reported. In the present study, fish populations were sampled from a reference
      stream and an effluent-dominated stream in north Texas, USA. Lepomis macrochirus,
      Ictalurus punctatus, Cyprinus carpio, and Pomoxis nigromaculatus were killed; the
      liver, brain, and lateral filet tissues dissected; and the tissues stored at -80
      degrees C until analysis. Fish tissues were extracted using solid-phase
      extraction and then analyzed by gas chromatography-mass spectrometry in the
      negative chemical ionization mode. The selective serotonin reuptake inhibitors
      (SSRIs) fluoxetine and sertraline and the SSRI metabolites norfluoxetine and
      desmethylsertraline were detected at levels greater than 0.1 ng/g in all tissues
      examined from fish residing in a municipal effluent-dominated stream. To our
      knowledge, the present study is the first report of SSRI residues in fish
      residing within municipal effluent-dominated systems.

PMID- 15720010
TI  - Relevance of generic and site-specific species sensitivity distributions in the
      current risk assessment procedures for copper and zinc.
AB  - Species sensitivity distributions (SSD) were constructed using acute toxicity
      data of various cladoceran species collected in five different aquatic systems.
      The aim of this research was to study the relative acute cladoceran community
      sensitivity in different aquatic systems. Current risk assessment procedures are
      based upon hypothetical communities and do not take into account variation in
      species composition and tolerance between aquatic communities. Two metals, copper
      and zinc, were used as model toxicants. To establish comparative sensitivity, a
      standard medium (International Organization for Standardization [ISO]) was used.
      The generic SSD (log-normal distribution) based on toxicity data obtained in this
      standard medium for all species (collected at all sites) resulted in a hazardous
      concentrations that protects 95% of the species occurring in a (hypothetical)
      ecosystem (i.e., hazardous concentration protecting 95% of the species of the
      hypothetical ecosystem [HC5]) of 6.7 microg Cu L(-1) (90% confidence limits: 4.2
      10.8) and 559 microg Zn L(-1) (375-843). This generic SSD was not significantly
      different from the site-specific SSDs (i.e., constructed with species only
      occurring at a specific site). Mean community sensitivity (the geometric mean of
      48-h 50% effective concentration [EC50] values of species within a community)
      among sites varied within a factor of 2 (between 17.3 and 23.6 microg Cu L(-1)
      for Cu and between 973 and 1,808 microg Zn L(-1) for Zn), and HC5s varied within
      a factor of 4 for copper (between 4.5 and 17.3 microg Cu L(-1)) and 7 for zinc
      (between 194 and 1,341 microg Zn L(-1)). For copper, the HC50 of our generic SSD
      was significantly lower than the one based on literature toxicity data of
      cladoceran species (which were recalculated to the hardness of our standard
      medium). In contrast, no significant differences were observed between the
      generic SSD and the literature-based SSD for zinc. It is suggested that the
      community sensitivity of different cladoceran populations is similar among
      aquatic systems and is not dependent on the species composition.

PMID- 15720011
TI  - Mode of action and aquatic exposure thresholds of no concern.
AB  - Threshold concepts of toxicological concern are based on the possibility of
      establishing an exposure threshold value for chemicals below which no significant
      risk is to be expected. The objective of the present study is to address
      environmental thresholds of no toxicological concern for freshwater systems
      (ETNCaq) for organic chemicals. We analyzed environmental toxicological databases
      (acute and chronic endpoints) and substance hazard assessments. Lowest numbers
      and 95th-percentile values were derived using data stratification based on mode
      of action (MOA; 1 = inert chemicals; 2 = less inert chemicals; 3 = reactive
      chemicals; 4 = specifically acting chemicals). The ETNCaq values were derived by
      multiplying the lowest 95th percentile values with appropriate application
      factors; ETNCaq,MOA1-3 is approximately 0.1 microg/L. A preliminary analysis with
      complete MOA stratification of the databases shows that in the case of MOA1 or
      MOA2, the ETNCaq value could be even higher than 0.1 microg/L. A significantly
      lower ETNCaq,MOA4 value was observed based on the long-term toxicity information
      in the European Centre for the Ecotoxicology and Toxicology of Chemicals
      database. Application of the ETNCaq value in a tiered risk-assessment scheme may
      help chemical producers to set data-generation priorities and to refine or reduce
      animal use. It also may help to inform downstream users concerning the relative
      risk associated with their specific uses and be of value in putting environmental
      monitoring data into a risk-assessment perspective.

PMID- 15720012
TI  - A comparison between the multimedia fate and exposure models CalTOX and uniform
      system for evaluation of substances adapted for life-cycle assessment based on
      the population intake fraction of toxic pollutants.
AB  - In life-cycle assessment (LCA) and comparative risk assessment, potential human
      exposure to toxic pollutants can be expressed as the population intake fraction
      (iF), which represents the fraction of the quantity emitted that enters the human
      population. To assess the influence of model differences in the calculation of
      the population iF ingestion and inhalation iFs of 365 substances emitted to air,
      freshwater, and soil were calculated with two commonly applied multimedia fate
      and exposure models, CalTOX and the uniform system for evaluation of substances
      adapted for life-cycle assessment (USES-LCA). The model comparison showed that
      differences in the iFs due to model choices were the lowest after emission to air
      and the highest after emission to soil. Inhalation iFs were more sensitive to
      model differences compared to ingestion iFs. The choice for a continental
      seawater compartment, vertical stratification of the soil compartment, rain and
      no-rain scenarios, and drinking water purification mainly clarify the relevant
      model differences found in population iFs. Furthermore, pH correction of chemical
      properties and aerosol-associated deposition on plants appeared to be important
      for dissociative organics and metals emitted to air, respectively. Finally, it
      was found that quantitative structure-activity relationship estimates for
      superhydrophobics may introduce considerable uncertainty in the calculation of
      population intake fractions.

PMID- 15720013
TI  - It takes a village.

PMID- 15720014
TI  - Making progress.

PMID- 15720016
TI  - Payment. BBA II: the sequel.

PMID- 15720017
TI  - Management. Culture club.

PMID- 15720019
TI  - Design & construction. ED of the future.

PMID- 15720018
TI  - Patient care. Open all hours.

PMID- 15720020
TI  - Management: aiming high.

PMID- 15720021
TI  - Goverance. Helping leaders.

PMID- 15720022
TI  - Data page: patient safety & governance.

PMID- 15720023
TI  - Witnessing.

PMID- 15720024
TI  - Health care's new behemoths.
AB  - Merger mania has been sweeping the insurance industry for years; what's raising
      eyebrows these days is the sheer pace of consolidation and the startling size of
      the plans being created. What are the implications of these megaplans for
      hospitals and for health care in general? As their clout in the marketplace
      increases, so does the scrutiny they're coming under.

PMID- 15720025
TI  - Zeroing in.
AB  - Up to now, most hospitals' patient satisfaction surveys have looked at the big
      picture, querying patients on their impressions of the organization as a whole.
      Increasingly, hospitals are focusing on so-called microsystems, asking how
      patients perceive their care and experiences in specific dinical units. It's in
      those units that perceptions take root.

PMID- 15720026
TI  - High-tech tools transform the operating room.
AB  - This installment of our quarterly Clinical Management series examines how the
      hospital operating room is becoming a safer place for patients. Thanks to such
      technological breakthroughs as 3-D images, virtual patients and robots, surgeons
      can operate with more accuracy and efficiency.

PMID- 15720027
TI  - The health care work force.
AB  - This month's gatefold examines the distribution of the health care workforce
      state by state. It also compares the commitment level of health care workers with
      workers in other fields and within health care by job category and organization
      type.

PMID- 15720028
TI  - Most freestanding hospitals do not conduct leadership succession planning.

PMID- 15720029
TI  - Devoting more staff to infection control could bring significant clinical and
      financial benefits.

PMID- 15720030
TI  - Progress in end-of-life care stymied by research obstacles, Medicare
      requirements.

PMID- 15720031
TI  - The challenges ahead.

PMID- 15720032
TI  - Toxicological effects of mainstream whole smoke solutions on embryonic movements
      of the developing embryo.
AB  - Cigarette smoking is unrivaled among developmental toxicants in terms of total
      adverse impact on the human population. Maternal tobacco use during pregnancy
      adversely affects prenatal and postnatal growth and increases the risk of
      behavioral and developmental defects in children and adolescents. In the current
      study, the effects of different preparations of nicotine and mainstream whole
      smoke solutions (MSWSS) on embryonic movements during neonatal development were
      examined in vivo, using the chicken embryo model, recorded in real-time by a
      video camera. It was observed that low doses of nicotine induced hyperactivity
      and higher doses induced hypoactivity. Accordingly, a significant (p < 0.01)
      decrease in movements was observed by application of 10 microg of nicotine and
      different preparations of MSWSS. A dose-dependent decrease in embryonic movements
      was observed, which did not recover by the end of experiment. It was concluded
      that nicotine could alter embryonic movements, which are important during
      embryogenesis for differentiation and maturation of the body systems.

PMID- 15720033
TI  - Toxicity of hexamethylenediamine.
AB  - Hexamethylendiamine (HMDA; CAS No. 124-09-4; 6055-52-3 for the dihydrochloride
      salt) is moderately toxic following acute doses/exposures with oral lethal doses
      in rats ranging from 750 to 1500 mg/kg. HMDA is extremely irritating to the skin
      and eyes and is not a sensitizer in guinea pigs. Repeated exposure inhalation
      studies have defined the upper respiratory tract to be the first target of HMDA.
      The irritation seen is proportional to the exposure concentration. Systemic
      damage is limited. Genetic testing is not extensive, but there is no indication
      of activity. HMDA is neither a developmental nor a reproductive toxin, but in one
      developmental study, the fetal No-observed-adverse-effect-level (NOAEL) was lower
      than that of the maternal animal. No carcinogenicity studies have been conducted.
      Documented human experience is limited, but indications of HMDA's irritative
      properties are found in the literature. HMDA does not persist or bioaccumulate in
      the environment. The chemical is not particularly toxic to fish and aquatic
      invertebrates but is quite toxic to algae. HMDA is rapidly absorbed and
      metabolized by the rat with little tissue storage.

PMID- 15720034
TI  - Effects of CKD-602, a new camptothecin anticancer agent, on pregnant does and
      embryo-fetal development in rabbits.
AB  - CKD-602 is a newly developed camptothecin anticancer agent. Preclinical studies
      suggest that it may have greater antitumor activity and lower toxicity than other
      camptothecin anticancer agents. The potential of CKD-602 to induce developmental
      toxicity was investigated in the New Zealand White rabbit. Seventy-two
      artificially inseminated females (artificial insemination=day 0) were distributed
      among three treatment groups and a control group. CKD-602 was at dose levels of
      0, 0.024, 0.048, or 0.096 mg x kg(-1) x day(-1) administered intravenously to
      pregnant does from days 6 to 18 of gestation. All does were subjected to
      caesarean section on day 28 of gestation. At 0.096 mg x kg(-1) x day(-1), 2 cases
      of abortion and 3 cases of death in pregnant rabbits were found in late
      gestation. In addition, an increase in the embryonic resorptions and a decrease
      in the litter size were found. At 0.048 mg x kg(-1) x day(-1), a single doe
      aborted on gestational day 26. An increase in the embryonic resorptions and fetal
      morphological alterations and a decrease in the litter size were also found.
      There were no signs of maternal toxicity or developmental toxicity at 0.024 mg x
      kg(-1) x day(-1). The results show that 13-day repeated intravenous dose of CKD
      602 during the major organogenetic period in rabbits produces increased incidence
      of abortion and death, increased number of embryonic resorptions and fetal
      morphological alterations, and decreased litter size at dose levels of above
      0.048 mg x kg(-1) x day(-1). In the current experimental conditions, the no
      observed-adverse-effect levels (NOAELs) of CKD-602 are considered to be 0.048 mg
      x kg(-1) x day(-1) for does and 0.024 mg x kg(-1) x day(-1) for embryo-fetal
      development.

PMID- 15720035
TI  - Evaluation of the toxicity and teratogenity of six commercial textile dyes using
      the frog embryo teratogenesis assay-Xenopus.
AB  - Potential developmental toxicities of six different textile dyes were evaluated
      using the frog embryo teratogenesis assay-Xenopus (FETAX). Xenopus laevis embryos
      were exposed to astrazon red FBL, astrazon blue FGRL, remazol red RR, remazol
      turquoise blue G-A, cibacron red FN-3G, and cibacron blue FN-R from stage 8 to 11
      for a 96-h exposure period in static renewal test conditions. A minimum of 17
      concentration-response tests were performed with tested dyes, excluding a control
      group for each dye. Median lethal concentration (LC50), malformation (EC50), non
      observed adverse effect concentration (NOAEC), and lowest observed adverse effect
      concentration (LOAEC) were calculated. Also, teratogenic index (TI), minimum
      concentration to inhibit growth (MCIG), and MCIG/LC50 values were determined for
      each of the tested dyes. Characteristic abnormalities induced by a given test
      material were determined by the relationship between concentration and dye in the
      study. Results from these studies suggested that each tested dye is teratogenic
      for X. laevis embryos. The lowest LC50 was determined for astrazon red exposure
      corresponding to a value of 4.73 mg/L. The LC50 value was similar for this dye
      and astrazon blue; the highest TI was calculated for astrazon blue exposure.
      Tests with X. laevis indicated that each of the tested compounds possessed
      teratogenic potential with varying degrees of potency: astrazon blue FGRL >
      remazol turquoise blue G-A > astrazon red FBL > cibacron blue FN-R > cibacron red
      FN-3G > remazol red RR. Different types of malformations occurred in the embryos,
      depending on concentration and dye. From these results, we can suggest that
      astrazon blue is the most toxic compound, but that the others are also highly
      toxic and teratogenic substances for X. laevis embryos. Results of the study
      confirmed that the FETAX assay can be useful in an integrated biological hazard
      assesment for the preliminary screening of textile dye stuff.

PMID- 15720036
TI  - Developmental lead exposure induces depressive-like behavior in female rats.
AB  - The involvement of neurotoxicants in the etiology of emotional pathologies is
      becoming an issue in neurotoxicology. Lead (Pb) exposure during childhood has
      been associated with increased impulsivity, aggressivity, and delinquency.
      Considering the paucity of experimental studies investigating the involvement of
      developmental Pb exposure in emotional disorders, our objective was to
      investigate whether Pb exposure during pregnancy and/or lactation could be
      related to depressive symptoms in adult male and female rats. Wistar dams
      received 10 mg of Pb, as Pb acetate, or 13.4 mg of Na acetate, by gavage, daily,
      during pregnancy and lactation. By cross-fostering at the time of birth, pups
      were either exposed to Pb or Na acetate during pregnancy only, lactation only, or
      during both pregnancy and lactation. At 70 days of age, animals were submitted to
      the open-field test followed by the forced swimming test. Pb levels were measured
      in the blood of dams (weaning) and pups (after behavioral evaluation). The
      results demonstrated that exposure to Pb during both pregnancy and lactation
      induced, in males, an increased emotionality state detected in the open-field
      test, and in females, depressive-like behavior detected in the forced swimming
      test. These alterations were observed at residual blood Pb levels (i.e., around 5
      microg/dL).

PMID- 15720037
TI  - Penetration of ammonium perfluorooctanoate through rat and human skin in vitro.
AB  - Rat and human epidermal membranes were mounted onto in vitro diffusion cells with
      an exposure area of 0.64 cm2, and skin integrity was confirmed using electrical
      impedance. Following membrane selection, Fluorad FC-118, a 20% aqueous solution
      of ammonium perfluorooctanoate (AFPO), was applied to the epidermal surface of
      each skin replicate at approximately 150 microL/cm2 and the donor chamber opening
      occluded with Parafilm. Serial receptor fluid samples were collected hourly from
      1 to 6 h and at 12, 24, 30, and 48 h and analyzed by liquid chromatography-mass
      spectrometry (LC-MS) for APFO anion (PFO-). For rat skin, the time to steady
      state penetration (6500+/-3000 ng APFO x cm(-2) x h(-1)) occurred in less than 12
      h, which was sustained until termination (48 h). Based on the concentration of
      the applied test material, the permeability coefficient (Kp) for APFO in rat skin
      was calculated to be 3.25+/-1.51 x 10(-5) cm/h. By end of the 48-h exposure
      period, only a small portion of the total APFO applied (1.44+/-1.13%) had
      penetrated through rat skin. For human skin, steady-state penetration of APFO
      (190+/-57 ng APFO x cm(-2) x h(-1)) was reached by 12 h. Based on the
      concentration of the applied test material, the permeability coefficient for APFO
      in human skin was calculated to be 9.49+/-2.86 x 10(-7) cm/h. By the end of the
      48-h exposure period, only a negligible amount of the total APFO applied (0.048+/
      0.01%) had penetrated through human skin. Thus, under infinite dose and occlusive
      conditions, the steady-state penetration of APFO from a 20% solution was
      approximately 34-fold faster through rat skin than human skin.

PMID- 15720038
TI  - Chronic high doses of thioacetamide followed by vitamin A modify dolichol,
      dolichol isoprenoids, and retinol content in rat liver cells.
AB  - Our line of researches follows the hypothesis that dolichol and retinol
      metabolism might be interrelated and involved in liver fibrosis. To this end, in
      this study rats were subjected to chronic treatment with thioacetamide (TAA) (300
      mg/L liquid diet) for 1 and 2 months and, after liver damage had occurred,
      supplemented with vitamin A before sacrifice. Dolichol, dolichol isoprene units,
      and retinol content were determined in isolated parenchymal and sinusoidal liver
      cells (hepatic stellate cells; Kupffer cells; sinusoidal endothelial cells).
      Dolichol increased in hepatocytes after TAA treatment, with or without vitamin A.
      Dolichol decreased in the other cells. Retinol in general decreased. In
      hepatocytes, retinol decreased only on normal nutrition, while the vitamin A load
      was taken up normally. The percentages of dolichol isoprene units (Dol-16 to Dol
      20, in rats) confirm that Dol-18, which was not modified in percentage by TAA on
      normal nutrition, did not increase after vitamin A, as it did in control cells (7
      12%). The behavior of Dol-18 was similar in all the cells studied. Vitamin A
      might reveal a latent damage produced by TAA on dolichol homologues. These data
      support previous hypotheses that the action of TAA depends on the administration
      modality, the dosage, and the diet, and that Dol-18 might have different
      functions and compartmentalization in the cells. Furthermore, the results support
      the hypothesis that dolichol chain length might be interrelated with retinol
      metabolism, perhaps through their metabolites.

PMID- 15720039
TI  - A convenient fluorometric method to study sulfur mustard-induced apoptosis in
      human epidermal keratinocytes monolayer microplate culture.
AB  - Sulfur mustard [SM; bis-(2-chloroethyl) sulfide], which causes skin blistering or
      vesication [(1991). Histo- and cytopathology of acute epithelial lesions. In:
      Papirmeister, B., Feister, A. J., Robinson, S. I., Ford, R. D., eds. Medical
      Defense Against Mustard Gas: Toxic Mechanisms and Pharmacological Implications.
      Boca Raton: CRC Press, pp. 43-78.], is a chemical warfare agent as well as a
      potential terrorism agent. SM-induced skin blistering is believed to be due to
      epidermal-dermal detachment as a result of epidermal basal cell death via
      apoptosis and/or necrosis. Regarding the role of apoptosis in SM pathology in
      animal skin, the results obtained in several laboratories, including ours,
      suggest the following: 1) cell death due to SM begins via apoptosis that proceeds
      to necrosis via an apoptotic-necrotic continuum and 2) inhibiting apoptosis
      decreases SM-induced microvesication in vivo. To study the mechanisms of SM
      induced apoptosis and its prevention in vitro, we have established a convenient
      fluorometric apoptosis assay using monolayer human epidermal keratinocytes (HEK)
      adaptable for multiwell plates (24-, 96-, or 384-well) and high-throughput
      applications. This assay allows replication and multiple types of experimental
      manipulation in sister cultures so that the apoptotic mechanisms and the effects
      of test compounds can be compared statistically. SM affects diverse cellular
      mechanisms, including endoplasmic reticulum (ER) Ca2+ homeostasis, mitochondrial
      functions, energy metabolism, and death receptors, each of which can
      independently trigger apoptosis. However, the biochemical pathway in any of these
      apoptotic mechanisms is characterized by a pathway-specific sequence of caspases,
      among which caspase-3 is a key member. Therefore, we exposed 80-90% confluent HEK
      cultures to SM and monitored apoptosis by measuring the fluorescence generated
      due to hydrolysis of a fluorogenic caspase-3 substrate (acetyl- or benzyl
      oxycarbonyl-Asp-Glu-Val-Asp-fluorochrome, also designated as AC-or Z-DEVD-
      fluorochrome) added to the assay medium. Fluorescence was measured using a plate
      reader. We used two types of substrates, one (Sigma-Aldrich, CASP-3-F) required
      cell disruption and the other (Beckman-Coulter CellProbe HT Caspase-3/7 Whole
      Cell Assay Kit) was cell permeable. The latter substrate was useful in
      experiments such as determining the time-course of apoptosis immediately
      following SM exposure without disruption (e.g., due to cell processing). In SM
      exposed HEK, fluorescence generated from the fluorogenic caspase-3 substrate
      hydrolysis increased in a time (0-24 h) and concentration (0.05, 0.1, 0.15, 0.2,
      0.3, 0.5 mM) dependent manner. SM caused maximum fluorescence at about 0.5 mM.
      However, at 2 mM SM, fluorescence decreased compared with 0.5 mM, which remains
      to be explained. Following 0.3 mM SM exposure, which is considered to be the in
      vitro equivalent of a vesicating dose in vivo (Smith, W. J., Sanders, K. M.,
      Ruddle, S. E., Gross, C. L. (1993). Cytometric analysis of DNA changes induced by
      sulfur mustard. J. Toxicol.-Cut. Ocular Toxicol. 12(4):337-347.), a small
      fluorescence increase was observed at 6 to 8 h, which was markedly higher at 12
      h. At 24 h, all SM concentrations increased fluorescence. Fluorescence increase
      due to SM was prevented 100% by a caspase-3-specific peptide inhibitor AC-DEVD
      CHO (acetyl-Asp-Glu-Val-Asp-aldehyde, 0.1 mM), but less effectively by a general
      caspase inhibitor Z-VAD-FMK (benzyl oxycarbonyl-Val-Ala-Asp-fluoromethylketone,
      0.01 mM), indicating that the fluorescence increase was due to caspase-3-mediated
      apoptosis. These results suggest potential applications of this method to study
      apoptosis mechanisms involving caspase-3 substrates and possibly those involving
      other caspase substrates.

PMID- 15720040
TI  - Induction of apoptosis by cationic amphiphilic drugs amiodarone and imipramine.
AB  - Phospholipidosis is the excessive accumulation of intracellular phospholipids in
      cell lysosomes. Drugs that induce this disease often share common physiochemical
      properties and are collectively classified as cationic amphiphilic drugs (CADs).
      Although the cause of phospholipidosis and morphologic appearance of affected
      lysosomes have been studied extensively, less is known about the physiologic
      effects of the condition. In the current study, U-937 cells were incubated with
      the CADs amiodarone (2.5-10 microg/mL) and imipramine (2.5-20 microg/mL).
      Treatment of U-937 cells with these compounds for 96 h resulted in concentration
      related increases in phospholipids, as assessed by flow cytometry using the
      fluorophore nile red. These results were verified by measuring the concentrations
      of choline-derived phospholipids, which were significantly increased in drug
      treated cells. Cell number in amiodarone (10 microg/mL) and imipramine (20
      microg/mL) cultures following the 96-h incubation period were markedly reduced
      compared to control cultures. These observations suggested that accumulation of
      cellular phospholipids could inhibit cell proliferation. Flow cytometric analysis
      revealed a decrease in the percentage of cells in the S-phase of the cell cycle
      following drug treatment, yet DNA replication still occurred in a significant
      portion of cells. Interestingly, amiodarone and imipramine induced apoptosis in U
      937 cells as shown by annexin V-FITC staining and DNA fragmentation. Enzymatic
      assays demonstrated that amiodarone and imipramine induced the activity of
      caspases 2 and 3. These results suggest that disruption of cell lysosomes in U
      937 cells following accumulation of phospholipids does not cause a cell cycle
      arrest but instead induces apoptosis by activation of caspase pathways.

PMID- 15720041
TI  - The metabolic syndrome.

PMID- 15720042
TI  - Retrospective analysis: consensus statement of the hypertension in African
      Americans working group of the International Society on Hypertension in Blacks
      (ISHIB).

PMID- 15720043
TI  - Is high density lipoprotein cholesterol useful in diagnosis of metabolic syndrome
      in native Africans with type 2 diabetes?
AB  - BACKGROUND: High-density lipoprotein (HDL) hypocholesterolemia predicts metabolic
      syndrome among Caucasians and is one of the World Health Organization (WHO)
      diagnostic criteria of the syndrome. Plasma lipid levels are, however, influenced
      by genetic and environmental factors. OBJECTIVE: To determine the relationship
      between HDL cholesterol and metabolic syndrome among native Africans with type 2
      diabetes. METHODS: Indigenous Nigerians with type 2 diabetes (N = 254) aged 35-80
      years (mean: 52.0 +/- 11.7 years) with male:female ratio of 1.5:1 were studied
      prospectively. Outcome measures included anthropometric indices, plasma lipid
      concentrations, uric acid, microalbuminuria, and predictive values. RESULTS: Of
      the 254 diabetic patients, 150 (54.3%) had metabolic syndrome. Dyslipidemia
      occurred in 184 (72.4%) patients. Of these, 54 (29.4%) had HDL
      hypocholesterolemia. Mean HDL cholesterol among patients with HDL
      hypocolesterolemia and those with normocholesterolemia were 32.4 +/- 5.7 mg/dL
      and 51.3 +/- 9.9 mg/dL, respectively. Prevalence of metabolic syndrome did not
      differ significantly between the two groups (56% vs 70.4%; P = .08). Linear
      regression analysis showed no association between HDL cholesterol and metabolic
      syndrome (r = 0.01; P = .2), body mass index (r = 0.02; P = .4), waist
      circumference (r = 0.07; P = .42) and microalbuminuria (r = 0.03; P = .8). A
      positive correlation occurred between HDL cholesterol and triglyceride
      concentrations (r = 0.6). The sensitivity, specificity, and positive and negative
      predictive values of HDL hypocholesterolemia in the diagnosis of metabolic
      syndrome were 25%, 84.6%, 70.4%, and 44%, respectively. CONCLUSION: High-density
      lipoprotein cholesterol may not be a reliable diagnostic tool of metabolic
      syndrome among native Africans with type 2 diabetes.

PMID- 15720044
TI  - Ethnic, gender, and age-related differences in treatment and control of
      dyslipidemia in hypertensive patients.
AB  - BACKGROUND: Demographic differences in management of concomitant lipid disorders
      among hypertensive patients may contribute to health disparities. OBJECTIVES:
      Assess demographic differences in lipid control rates and treatment patterns
      among dyslipidemic hypertensive patients in primary care. METHODS: Demographic
      information, blood pressure, LDL-cholesterol, and medications were obtained on
      72,351 hypertensive patients from 262 primary care providers at 69 sites in the
      Southeast. Analysis focused on a dyslipidemic hypertensive subset. RESULTS: Among
      72,351 hypertensives, 38,116 were dyslipidemic. Fifty-two percent of patients did
      not have a cholesterol measurement documented in the past year. Women and
      patients <40 years old were less likely to have an annual cholesterol measurement
      than men and older, same-race counterparts (P < or = .001). Thirty-five percent
      of all hypertensive dyslipidemic patients had not been prescribed any anti
      lipidemic medication, whereas 15% were on a statin and another anti-lipidemic.
      Women received fewer statin prescriptions than men (47.7% vs 65.1%, P < or =
      .0001). Fewer African Americans (AA) than Caucasians (C) reached LDL levels of
      <100 or <130 mg/dL (P < or = .0001). Among C and AA patients, those <40 years old
      were less likely than older, same-race counterparts to have reached LDL < 100 or
      <130 mg/dL (p < or = 001). Younger patients had fewer annual cholesterol
      measurements and were less likely to receive antilipidemic medication and to have
      LDL controlled than older, same-race counter-parts in each ethnic group (P < or =
      .0001). CONCLUSIONS: Demographic characteristics of hypertensive patients,
      especially younger age group, are associated with significant differences in
      diagnostic testing, treatment, and control of hyperlipidemia in primary care.
      This primary care information can be used to guide education and policy
      interventions to improve outcomes and reduce disparities.

PMID- 15720045
TI  - Race differences in cardiovascular and cortisol responses to an interpersonal
      challenge in women who are family caregivers.
AB  - OBJECTIVES: To examine race differences in psychosocial and psychophysiological
      responses to family caregiving. DESIGN: Participants completed paper-and-pencil
      surveys and were exposed to a laboratory-based interpersonal challenge that
      included a period of rest, an interpersonal challenge, and a period of recovery.
      SETTING: A university research laboratory. PARTICIPANTS: Sixteen Caucasian and 12
      African-American postmenopausal (64 +/- 10 years) women who were caregivers to a
      family member with dementia. MEASURES: Psychosocial functioning included self
      reported perceived stress, caregiver burden, social support, and caregiving
      meaning. Systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR)
      were measured every two minutes during the rest, challenge, and recovery.
      Salivary cortisol was measured at rest and 15-minutes post-challenge. RESULTS:
      There was a Race x Task interaction for SBP and HR but not DBP reactivity.
      African-American women showed greater reactivity than Caucasian women. The
      magnitude of this interaction was large. African-American women also reported
      greater caregiving from meaning than Caucasian women. In contrast, significantly
      more African Americans (58%) than Caucasians (14%) showed cortisol reactivity
      from rest to 15-minutes post-challenge. CONCLUSIONS: The differential pattern of
      physiologic responses is consistent with studies outside of the caregiving
      literature, and suggests that caregiving may be perceived as more effortful among
      Caucasian women and less controllable among African-American women.

PMID- 15720046
TI  - Prevalence, treatment, and control of hypertension among African Americans and
      Caucasians at primary care sites for medically under-served patients.
AB  - CONTEXT: Hypertension is a major contributor to ethnic disparities in
      cardiovascular disease, especially among low-income African Americans in the
      southeast United States. OBJECTIVE: To assess differences between African
      Americans and Caucasians in the prevalence, treatment, and control of
      hypertension in outpatient clinics for under-served patients in South Carolina.
      DESIGN: A random sample of outpatient charts on 7795 adults was abstracted from
      31 primary care clinics providing health care for approximately 180,000 medically
      under-served patients. Variables included visit dates, blood pressures (BP),
      diagnosis of hypertension, and medications. RESULTS: Data were abstracted from
      outpatient medical records on 4694 African Americans (1483 men, 3195 women, 16
      gender unknown, age 46.8 +/- 0.3 years) and 2540 Caucasians (1031 men, 1492
      women, 17 gender unknown, age 47.7 +/- 0.4 years). The prevalence of hypertension
      was greater in African Americans than Caucasians (47.6% vs 31.0%, P < .001). The
      percentages of hypertensive African Americans and Caucasians receiving BP
      medications were similar (83.4% vs 81.6%, P=NS). Although African-American
      hypertensives were more likely than Caucasian hypertensives to receive diuretics
      and calcium channel blockers and less likely to receive beta-blockers, the number
      of BP medications was similar for both groups (1.44 +/- 0.02 vs 1.40 +/- 0.04,
      P=NS). Despite comparable treatment, African Americans were less likely than
      Caucasians to have BP controlled to <140/90 mm Hg at the most recent clinic visit
      (40.9% vs 46.3%, P=.01). CONCLUSIONS: In healthcare settings for medically under
      served patients, the greater prevalence and lesser control of hypertension,
      despite similar treatment intensity, may contribute to higher rates of
      cardiovascular disease among African Americans than Caucasians.

PMID- 15720047
TI  - Rural and semi-urban differences in salt intake, and its dietary sources, in
      Ashanti, West Africa.
AB  - OBJECTIVES: To provide a socioeconomic profile of rural and semi-urban settings
      in Ashanti, West Africa and to investigate the relationship between urbanization
      and sources of salt in the diet. SETTING: 12 villages (6 rural, 6 semi-urban)
      participating in a cluster randomized controlled trial of a health promotion in
      the Ashanti region of Ghana. PARTICIPANTS: 1013 adult men (N = 385) and women (N
      = 628), aged 40-75. METHOD: Between June 2001 and June 2002, participants
      completed a detailed questionnaire on demography, occupation and education,
      housing, radio and television use, personal and family medical history, drug
      therapy, smoking, alcohol consumption, and diet. RESULTS: 532 subjects lived in
      semi-urban and 481 in rural communities. Ninety-two percent of the participants
      were of the Ashanti tribe and 94% spoke Twi. The semi-urban villages were closer
      to Kumasi, the second largest city in Ghana, had larger population (1727 vs 1100
      people) and household sizes (14.6 vs 8.8 persons per household; P < .001), had
      fewer farmers (53% vs 81%; P < .001) and more traders (22% vs 7%; P < .001), and
      had more homes with electricity (81% vs 17%; P < .001) and piped water (28% vs
      0.2%; P < .05). Semi-urban villagers had higher systolic blood pressure than
      rural villagers (129 vs 121 mm Hg difference 8 mm Hg [95% CI 5-11]; P < .001).
      Salt is almost invariably added to food in cooking (98%), and salted foods such
      as fish and meat are eaten in both communities. Salt is often added at the table
      (52%), more often in rural villages than in semi-urban settings (59% vs 45%; P <
      .01), although the total salt consumed as measured by urinary sodium was similar
      (99 vs 103 mmol/day). Potassium levels were higher in rural villages (58 vs 40
      mmol/day difference 18 mmol/day [95% CI 11-26]; P < .001). CONCLUSIONS: In this
      mainly farming community were clear differences in housing, population structure,
      and blood pressure between rural and semi-urban communities. While no significant
      differences were in the amount of salt consumed, the sources of salt differed
      between rural and semi-urban settings. Finally, rural villagers ate more
      potassium than semi-urban participants.

PMID- 15720049
TI  - A short acculturation scale for Mexican-American populations.
AB  - Acculturation is important to examine variables that differentiate members of
      ethnic groups so that interventions can be appropriately targeted. By using a
      population-based sample of Mexican-origin adults, we sought to validate an
      acculturation scale for Mexican-American populations. The acculturation
      instrument included eight items adapted from the Acculturation Rating Scale for
      Mexican Americans (ARSMA). By using principal component analysis, we calculated
      eigenvalues for the eight items. The first principal component accounted for 66%
      of the variance. Language spoken most of the time, by itself, explained 62.4% of
      the variance of the full model, whereas birthplace, by itself, accounted for 74%.
      Slight increases in correlation values were observed beyond a four-item model
      that included language spoken most of the time, language thought, ethnic
      identity, and birthplace. Future studies should compare this scale with other
      multidimensional scales.

PMID- 15720048
TI  - Racial/ethnic disparity and predictors of leisure-time physical activity among
      U.S. men.
AB  - OBJECTIVES: To examine racial/ethnic disparity in and predictors of leisure-time
      physical activity (LTPA) among men. METHODS: We used the National Health
      Interview Surveys (NHIS) 1999-2000 data, a multistage probability sampling design
      producing a U.S. representative sample of 23,459 adult males. Data were analyzed
      using multinomial logistic regression. RESULTS: The likelihood of engaging in
      irregular or regular LTPA was associated with younger age, being unmarried, lower
      household sizes, higher levels of education and income, home ownership, U.S.
      citizenship, perceived better health status, contact with a health professional
      within a year, being a non-smoker, living in the West, and residing in a midsize
      metropolitan statistical area. Hispanics were significantly less likely to engage
      in regular LTPA than Whites and higher percentages of Hispanics were physically
      inactive in almost all age and education groups when compared to other races.
      Disparity between Whites and Blacks was less pronounced. Non-citizen Hispanics
      were twice as likely to be inactive than citizens and White non-citizens were 40%
      more likely to be inactive than citizens. Conversely, Black citizens were 20%
      more likely to be inactive than non-citizens. CONCLUSIONS: Racial/ethnic
      disparities exist after accounting for socio-demographic characteristics. Not
      being a citizen exacerbates the disparity between Hispanic and White men. While
      disparity did exist between Black and White men, this gap was not as large as
      between Hispanic and White men. Health-seeking behaviors, such as contact with a
      health professional and non-smoking status are modifiable and influence men of
      all racial and ethnic backgrounds to engage in LTPA.

PMID- 15720050
TI  - Cigarette advertising in Black, Latino, and White magazines, 1998-2002: an
      exploratory investigation.
AB  - OBJECTIVE: To examine the number, type (menthol vs non-menthol), brand (Black,
      White, Women's, Other), and size of cigarette ads in Black, Latino, and White
      magazines. METHOD: Analysis of digital photographs of 274 cigarette ads appearing
      in Ebony (Black), People (White), and People in Spanish (Latino) for the 4.5-year
      period of January 1998 to August 2002. RESULTS: Black magazines were 9.8 times
      and Latino magazines 2.6 times more likely than White magazines to contain ads
      for menthol cigarettes. Black and Latino magazines also contained significantly
      more ads for brands (Virginia Slims) that target women. CONCLUSIONS: The tobacco
      industry continues to target Blacks with menthol cigarette ads, appears now to be
      targeting Latinos similarly, and targets Black and Latino women with additional,
      tailored cigarette ads.

PMID- 15720051
TI  - Perceptions of participation in an observational epidemiologic study of cancer
      among African Americans.
AB  - PURPOSE: Recruitment and retention of African Americans in cancer research
      studies has become increasingly important. However, little is known about factors
      bearing on recruitment and retention in etiologic observational studies of
      cancer. We assessed perceptions and attitudes of African Americans towards
      participation in an observational epidemiologic study of cancer, and attitudes
      toward the data collection process. METHODS: Five focus groups, each lasting
      approximately 2 hours, were conducted. Participants were comprised of men and
      women between 41-65 years of age. A total of 35 adults from three rural and two
      urban counties in North Carolina participated. Data were analyzed using NVivo
      software. RESULTS: Four key themes emerged on the perception of participation and
      retention in an epidemiologic study of cancer: (1) fear of cancer prognosis; (2)
      conflicts between mistrust and trust in researchers; (3) comprehension of
      prospective study purpose, structure, and participation strategies; and (4) the
      necessity for and obligation to provide feedback. CONCLUSION: Results indicate
      that African Americans would be willing to participate in epidemiologic studies
      to identify etiologic risk factors for cancer. However, culturally appropriate
      efforts to thoroughly inform them of study process and progress are deemed
      essential for successful recruitment and retention.

PMID- 15720052
TI  - Racial/ethnic differences in screening for colon cancer: report from the New York
      Cancer Project.
AB  - OBJECTIVE: To determine whether racial/ethnic differences in colon cancer
      screening are independent of socioeconomic and personal risk factors. DESIGN:
      Baseline cross-section for a prospective cohort. METHOD: We recruited adults
      between 2000 and 2002 to undergo a questionnaire and venipuncture to study cancer
      risks. RESULTS: Among 5595 adults over 50 years old, 40.3% reported sigmoidoscopy
      or colonoscopy within the prior five years; rates were 48.0% for Whites, 32.8%
      for Blacks, 27.9% for Hispanics, 30.3% for Asians, and 33.3% for others.
      Adjusting for age, gender, access to care (as income and insurance), and risk
      profile (as cancer in family, smoking, and obesity), Blacks and Hispanics were
      less likely to have been screened than Whites. CONCLUSIONS: Screening for colon
      cancer is low, especially among racial/ethnic minorities. Sociocultural factors
      merit closer attention.

PMID- 15720053
TI  - Reproducibility of self-reported pap test utilization in middle-aged African
      American women.
AB  - Both clinicians who perform Pap tests and prescribe re-screens and public health
      officials, who periodically evaluate the success of Pap test screening programs,
      often depend on women to self-report their most recent Pap test. However,
      reliability of self-reported Pap test utilization is putatively low, and even
      lower in African-American women compared to Whites. Between 2001 and 2002, Pap
      test screening histories were obtained from 144 African-American women, aged 45
      to 64 years at two in-person interviews conducted three to six weeks apart.
      Reproducibility of self-reported Pap test was substantial (kappa=0.64; 95%
      confidence interval: .46-.82), with the highest agreement among women with
      greater income and educational attainment, and those who were younger. This level
      of reproducibility is likely sufficient both to evaluate the population coverage
      of public health screening programs and for prescribing re-screens among younger
      African-American women and those of higher income and education. Not using self
      reports to base clinic decisions may still be prudent among those with less
      education.

PMID- 15720054
TI  - Collecting information on race, Hispanic ethnicity, and birthplace of cancer
      patients: policies and practices in Connecticut hospitals.
AB  - OBJECTIVE: Cancer incidence, treatment, and prognosis show important disparities
      by race, Hispanic ethnicity, and birthplace, but hospital policies and procedures
      in obtaining this information are poorly documented. This study documented
      policies and procedures in a state (Connecticut) with a high-quality population
      based cancer registry. METHODS: Directors of medical records and/or admissions at
      all 30 hospitals were surveyed, and hospital records were abstracted for a sample
      of 220 minority (African-American/Black, Asian, and Hispanic) cancer patients
      diagnosed in 2000-2001 at three hospitals of various sizes. RESULTS: At least one
      staff member at 86% of the 28 responding hospitals reported a hospital policy to
      ask patients about their race, vs 25% for ethnicity and 57% for birthplace, and
      patient self-reports were reportedly used to obtain race in 100% of hospitals vs
      54% for ethnicity. Race was regarded as "very important" or "important" by staff
      at 89% of hospitals, vs only 46% for ethnicity and 61% for birthplace, and 68% of
      hospitals reported using a single item for both race and ethnicity. Results of
      record abstraction for the 220 minority patients at the three selected hospitals
      were generally consistent with data from surveys of hospital staff. Ethnicity was
      rarely recorded on any specific type of document, although preferred language was
      usually recorded. Disagreement in recorded race or ethnicity on different
      documents was rare (2%-3%). CONCLUSIONS: Efforts are needed to educate hospital
      staff on the importance of collecting information on Hispanic ethnicity and
      birthplace. Similar studies are needed in other states.

PMID- 15720055
TI  - Who trusts healthcare institutions? Results from a community-based sample.
AB  - OBJECTIVE: The goal of this research was to examine racial differences in trust
      in various healthcare institutions. METHOD: In telephone interviews, 195 Whites,
      183 Blacks, and 171 Latinos from Durham, NC indicated how often they trust
      various institutions (community doctors, local hospitals, county health
      department, insurance companies, and state and federal government) to do what is
      best for patients. RESULTS: In bivariate analyses, trust in various healthcare
      institutions was associated with race; Whites and Latinos trusted physicians more
      often than Blacks, and Latinos trusted the health department, insurance
      companies, and both government entities more often than Whites and Blacks (Ps <
      .01). In adjusted analyses controlling for marital status, financial status, and
      education, race was still associated with trust. Whites trusted physicians more
      often than Blacks, and Latinos trusted insurance companies, the state government,
      and the federal government more often than Whites and Blacks (Ps < .01).
      CONCLUSIONS: Racial differences in trust of healthcare institutions vary by
      institution type. Future studies of trust and interventions designed to improve
      trust must account for race and target institution differences.

PMID- 15720056
TI  - Access to health care in a rural area of the Philippines.
AB  - This study reports the results of a household survey requested by the mayor and
      community health officials in an under-served and understudied rural town in the
      Philippines. The study examines the extent and determinants of access to care.
      Results showed that 15% had a check-up in the previous year, despite 63%
      reporting a family history of chronic diseases. Multivariate regression analyses
      showed that having a usual source of care (P=.006) and education (P = .04) were
      predictors of having had a checkup the previous year. This study, which
      represents the first household survey assessing access to care in this rural
      Filipino population, provides empiric evidence supporting the need for health
      programs that will improve access to care and routine monitoring of chronic
      illness in this under-served, rural population.

PMID- 15720057
TI  - Suicidal ideation among African-American non-injection drug users.
AB  - The objective of the study was to explore correlates of suicidal ideation among
      African Americans in a community-based cohort in Baltimore, Md. Participants had
      initiated use of heroin, crack, or cocaine by means other than injection in the
      prior 10 years. An interview-administered questionnaire collected information
      regarding drug use history, depressive symptoms, drug dependence, and suicidal
      thoughts and attempts within the past six months. Multiple logistic regression
      was used to identify factors independently associated with suicidal ideation. Of
      148 persons, median age was 27 years, and 60.8% were female. Suicidal ideation
      was reported by 21.6% of participants. Those reporting suicidal ideation were
      significantly more likely to be dependent on two or more drugs (adjusted odds
      ratio=2.93, 95% confidence interval = 1.25, 6.88). Our findings underscore the
      need to integrate treatment for psychiatric comorbidity and drug dependence and
      target these services toward young, African-American drug users.

PMID- 15720058
TI  - Racial differences in analgesic/anti-inflammatory medication adherence among
      patients with osteoarthritis.
AB  - OBJECTIVES: This study examined the prevalence of self-reported adherence to
      medications for osteoarthritis (OA) and racial differences in adherence. METHODS:
      This was a cross-sectional survey of 156 Black and White veterans who were taking
      medications for OA. RESULTS: One quarter of participants reported sometimes
      forgetting to take their OA medications, 16% were sometimes careless about taking
      medications, and 27% sometimes stopped taking their medications when they felt
      better. Overall, 44% of participants reported at least one of these three
      behaviors. In a multivariable logistic regression model adjusting for demographic
      factors, OA severity, participatory decision making (PDM), and side effects,
      Black patients were more likely to report at least one nonadherent behavior (odds
      ratio [OR] = 2.25, 95% CI = 1.03-4.91). Patients with greater PDM scores were
      slightly less likely to report nonadherent behavior (OR = 0.95, 95% CI = 0.91
      0.99). DISCUSSION: Additional research is needed to examine factors underlying
      racial differences in adherence, to guide effective interventions.

PMID- 15720060
TI  - Can a culturally responsive model for research design bring us closer to
      addressing participation disparities? Lessons learned from cancer survivorship
      studies.
AB  - INTRODUCTION: Health disparities research demands the inclusion of traditionally
      excluded peoples. Additional complex issues weigh into health disparities or
      multicultural research including sociopolitical context, cultural context,
      network or community context, and micro-level or personal dimensions. CONCEPTUAL
      FRAMEWORK: This paper will present a work in progress based on psycho-oncology
      research: A Culturally Responsive Model for Research Design. The manuscript will
      describe the model's governing principles and practices employed to address these
      study components: 1) purpose of the research; (2) utilization of modified or new
      conceptual framework and operationalization; (3) methods and procedures; (4)
      participant and data safety and monitoring; (5) reliable and valid
      instrumentation; (6) drawing valid conclusions; (7) dissemination of findings;
      and (8) staff training. This paper will define these issues and present the
      guiding principles modeled to conduct culturally responsive research and increase
      research integrity. DISCUSSION: Cancer control research is an important part of
      the stated commitment to reduce cancer incidence, morbidity, and mortality and to
      increase health-related quality of life. Ethnic minorities are overrepresented in
      cancer burden, yet underrepresented in research. This paper is part of a movement
      to articulate practical models for designing culturally responsive, multicultural
      research. The model may have implications for increasing ethnic minority
      participation in research.

PMID- 15720059
TI  - Successfully recruiting a multicultural population: the DASH-Sodium experience.
AB  - Recruiting practices employed by the four clinical centers participating in the
      Dietary Approaches to Stop Hypertension (DASH)-Sodium trial were examined to
      assess the most successful method of obtaining participants and to describe
      pertinent learning experiences gained as a result of the trial. The primary
      recruitment strategies employed by each center were mass mailing brochures
      (direct, coupon packs, or other) and mass media (advertisements in newspapers,
      radio, and television spots). Of 412 randomized participants, 265 (64%) were from
      mass distribution of brochures, 62 (15%) mass media, and 85 (21%) were prior
      study participants, referred by word-of-mouth, or reported coming from screening
      events and presentations. Although the most successful method of recruitment was
      mass mailing brochures, three times as many brochures were distributed to obtain
      similar success as in the initial DASH trial.

PMID- 15720061
TI  - For the patient. Who trusts healthcare institutions? Results from a community
      based sample.

PMID- 15720062
TI  - For the patient. How much salt is used in Ashanti, West Africa?

PMID- 15720063
TI  - For the patient. Recruitment strategies for cancer research studies.

PMID- 15720064
TI  - For the patient. Do patients use prescribed medicine for osteoarthritis?

PMID- 15720065
TI  - For the patient. Scale to measure how Mexican-American populations fit into U.S.
      culture.

PMID- 15720066
TI  - For the patient. How Connecticut hospitals collect information on race, Hispanic
      ethnicity, and birthplace.

PMID- 15720067
TI  - Is the coccoid form of Helicobacter pylori viable and transmissible?

PMID- 15720068
TI  - Cloning and expression of vacA gene fragment of Helicobacter pylori with coccoid
      form.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) can transform, in vivo as well as in
      vitro, from dividing spiral-shaped forms into nonculturable coccoid forms, whose
      importance in disease transmission and antibiotic treatment failures is unclear.
      The aim of the present study was to clone and express the vacA gene of coccoid H.
      pylori and to infer its possible pathogenesis. METHODS: Firstly, coccoid form was
      obtained from strain NCTC 11637 by exposure to antibiotics in subinhibitory
      concentrations and collected. Secondly, vacA gene of the coccoid H. pylori was
      amplified by PCR. After being purified, the target fragment was cloned into
      plasmid pMD-18T, and the recombinant plasmid pMD-18T-vacA was transformed into E.
      coli JM109. The sequence of inserted fragment was analyzed. Thirdly, vacA gene
      from recombinant plasmid pMD-18T-vacA was digested with restriction enzyme and
      was inserted into expression vector pET32a (+). The positive recombinants were
      transferred into E. coli BL21 and identified by restriction enzyme digestion and
      PCR. Finally, the genetically engineered bacteria including pET32a (+)-vacA
      plasmids were induced by IPTG, the expression was analyzed by SDS-PAGE and gel
      densitometric scanning. RESULTS: The results revealed that vacA gene of 3888bp
      was obtained from the coccoid H. pylori genome DNA, recombinant plasmid pMD-18T
      vacA constructed were successfully digested by BamH I +Sac I, and the product of
      digestion was identical with the predicted 1. Sequence analysis also showed that
      the homology of coccoid and the reported original sequence was 99.8%. Plasmid
      pET32a (+)-vacA could express a specific 156kDa protein in E. coli BL21, and the
      protein accounted for 15.5% of the total protein of recombinant bacterial.
      CONCLUSIONS: The present data indicate that coccoid H. pylori contains complete
      vacA gene, and could synthesize its protein, which may be related to the disease
      relapse and transmission when coccoid H. pylori recovers virulence under suitable
      conditions.

PMID- 15720069
TI  - Development of hepatocellular carcinoma after successful management of esophageal
      variceal bleeding.
AB  - BACKGROUND: Endoscopic and pharmacological treatments significantly reduce
      recurrent esophageal variceal bleeding and improve the prognosis of cirrhotic
      patients. This study was aimed to evaluate the incidence, risk factors, treatment
      and prognosis of hepatocellular carcinoma after esophageal variceal bleeding.
      METHODS: Patients with esophageal variceal bleeding underwent endoscopic or
      pharmacological treatments to arrest acute bleeding or prevent rebleeding.
      Concurrently, patients were followed by periodic serum alpha-fetoprotein
      examinations and ultrasonography, aiming at early detection and possible
      treatment of hepatocellular carcinoma. RESULTS: Hepatocellular carcinoma
      developed in 79 of 370 patients (21.4%) during the 10-year follow-up. The
      cumulative incidence of hepatocellular carcinoma was 21.1% at the end of the
      third year, 39.3% at the end of the fifth year and 53.0% at the end of the tenth
      year. Small tumors (< or = 3 cm) were found in 64 patients (81.0%, monofocal
      tumors in 46 patients). Age, hepatitis B virus, hepatitis C virus, and alpha
      fetoprotein level > 20 ng/mL were factors associated with the risk of
      hepatocellular carcinoma development by multivariate analysis using Cox
      regression. Tumors were actively treated in 37 of 49 Child-Pugh A and B patients
      (75.5%) and 2 of 30 Child-Pugh C patients (6.7%). The median survival of all
      patients was 2.5 (range, 0.5 to 10.0) years. Development of hepatocellular
      carcinoma and serum bilirubin level were significantly associated with mortality
      in Child-Pugh A and B patients. CONCLUSIONS: Patients with esophageal variceal
      bleeding had a high risk of developing hepatocellular carcinoma. Surveillance on
      hepatocellular carcinoma could detect most tumors with small size. Hepatocellular
      carcinoma had an adverse impact on the survival of patients without advanced
      cirrhosis.

PMID- 15720070
TI  - Mucoepidermoid tumors of the lung: analysis of 11 cases.
AB  - BACKGROUND: Mucoepidermoid tumors (METs) of the trachea and bronchi are rare.
      They derive from the minor salivary gland tissue of the proximal tracheobronchial
      tree, and their clinical behaviors are still controversial. Herein, we analyze 11
      cases of MET to investigate its clinicopathological characteristics. METHODS: The
      medical records and pathological examinations of patients diagnosed with MET from
      May, 1995 to May, 2001 at the Division of Thoracic Surgery in Taipei Veterans
      General Hospital were retrospectively reviewed. RESULTS: There were 11 patients
      (7 male and 4 female) aged from 19 to 79 years, with a peak at the seventh and
      eighth decade. The mean age at diagnosis was 58.9 years, and 9 of these 11
      patients were symptomatic. No surgical mortality occurred. Three patients with
      low-grade tumors were all young females (less than 30 years). They were all alive
      without evidence of disease recurrence until the date of analysis, whereas the 5
      year survival of 8 patients with high-grade tumors was only 25%. Six patients
      with high-grade tumors received adjuvant therapy, but their prognoses remained
      poor. CONCLUSIONS: In the current study, METs occurred more frequently in male
      patients. Young female patients were preponderant to have low-grade tumors and
      therefore associated with better prognosis. Histological grading of the MET and
      the ability to achieve an anatomic resection are 2 most important factors that
      affect prognosis. Adjuvant therapy seems not to be effective in patients with
      high-grade MET.

PMID- 15720071
TI  - Effects of finasteride on prostate volume and prostate-specific antigen.
AB  - BACKGROUND: Finasteride was introduced to treat patients with benign prostatic
      hyperplasia (BPH) recently, and it has shown its effects in reduction of prostate
      volume and decrease of prostate-specific antigen (PSA). We want to know how and
      how much does finasteride affect prostate volume as well as PSA and prostate
      specific antigen density (PSAD), since PSA and PSAD are widely used as screening
      tools for early detection of prostate cancers. METHODS: Among 166 men with the
      diagnosis of BPH who received finasteride (5 mg/day) for 6 months, the serum PSA
      levels were measured. The prostate volumes before and after medication for a
      subgroup of 86 patients were measured by transrectal ultrasonography (TRUS).
      Paired t-test was used for the statistical analysis. The median percentage change
      in PSA of total 166 men and the median percentage changes in prostate volumes and
      PSAD of 86 men were also calculated. RESULTS: Among 166 men, the average serum
      PSA level was 2.48+/-2.02 ng/mL at baseline and 1.57+/-1.47 ng/mL at 6 months
      later. The median percentage change of serum PSA level was -44.26%. For 86
      patients who underwent TRUS evaluation the average prostate volume changed from
      39.83+/-21.10 mL to 33.62+/-20.52 mL. The median percentage change of prostatic
      volume was -17.80%. Also, the median percentage change in PSAD for these 86
      patients after medication was -38.67%. CONCLUSIONS: Finasteride does decrease the
      serum PSA level and PSAD as well as prostate volume in men with BPH treated with
      it for 6 months. Physicians prescribing finasteride for patients with symptomatic
      BPH should always keep in mind its effect on PSA and PSAD levels in order not to
      miss potential prostate cancers.

PMID- 15720072
TI  - The results of posterolateral lumbar fusion with bone chips from laminectomy in
      patients with lumbar spondylolisthesis.
AB  - BACKGROUND: This study was undertaken to assess the radiologic outcome of spinal
      fusion, with bone chips from laminectomy in patients with lumbar
      spondylolisthesis. METHODS: From January 1993 to September 2001, 95 patients with
      lumbar spondylolisthesis were managed and followed up well at our Orthopedic
      Division. All patients presented with persistent low back pain, radiculopathy and
      claudication. The diagnosis of lumbar spondylolisthesis was confirmed by plain
      radiographs of the lumbar spine, with lumbar spine computed tomography scan (CT
      scan) performed to identify other associated conditions. A near total posterior
      decompression laminectomy with foraminotomy and posterolateral lumbar fusion
      using bone chips from laminectomy as bone graft and reduction of the vertebral
      slip using transpedicle screws with Arbeitsgemeinschaft fur Osteosynthesefragen
      spinal fixators and Trifix Reduction Fixation spinal system implants, were
      instituted. Additional disectomies were performed in several patients with disc
      rupture as confirmed by CT-scan. Fusion was then assessed by plain lumbar
      radiographs done at 4, 8, and 24 months after operation. RESULTS: The outcome was
      good, with 88 (92.6%) cases attaining solid fusion, while failed fusion was noted
      in 7 (7.4%) cases. CONCLUSIONS: Proper decortication of the posterolateral
      vertebral gutter with removal of all soft tissues attached to the bone chips
      prior to the placement of bone graft were noted to be the most significant
      factors for spinal fusion. Fusion rate with bone chips from laminectomy was shown
      to be comparable to that of the iliac crest bone graft.

PMID- 15720073
TI  - Tuberculosis in a SARS outbreak.
AB  - Preoccupied with the diagnosis of SARS (severe acute respiratory syndrome) in a
      SARS outbreak, doctors tend to overlook other endemic diseases, such as
      tuberculosis. Incorrectly labeling a patient as SARS may result in serious
      consequences. Single isolation being not always possible, the patient may have to
      be isolated with a group of SARS patients. The following article reports how a
      young girl suffering from pulmonary tuberculosis was erroneously diagnosed as
      SARS in an outbreak. Isolated with other SARS patients, she was infected with the
      virus. The treatment of SARS and tuberculosis resulted in liver dysfunction.
      Fortunately, the patient recovered uneventfully. The importance of keeping an
      open mind in an outbreak is highlighted.

PMID- 15720074
TI  - Gastric schwannoma.
AB  - Gastrointestinal mesenchymal tumors are a group of tumors originated from the
      mesenchymal stem cells of the gastrointestinal tract, consisting of
      gastrointestinal stromal tumors (GIST), leiomyomas or leiomyosarcomas or
      schwannomas. Gastric schwannoma is a very rare gastrointestinal mesenchymal
      tumor, which represents only 0.2% of all gastric tumors and 4% of all benign
      gastric neoplasms. We report a 24-year-old girl who suffered from an episode of
      upper gastrointestinal bleeding. The endoscopic examination showed a round
      submucosal tumor with a central ulceration and bleeding over the high body of the
      stomach. Surgical resection of the tumor was performed. The pathological
      examination revealed a picture of spindle cell tumor that was strongly positive
      for S-100 protein stain, and non-reactive for CD34, CD117, actin, HHF-35, desmin,
      melan-A and HMB-45, consistent with gastric schwannoma. The literature is
      reviewed.

PMID- 15720075
TI  - Facial paralysis caused by metastasis of breast carcinoma to the temporal bone.
AB  - Metastatic tumors to the temporal bone are very rare. The most common sites of
      origin of temporal bone metastases are breast, lung, kidney, gastrointestinal
      tract, larynx, prostate gland, and thyroid gland. The pathogenesis of spread to
      the temporal bone is most commonly by the hematogenous route. The common otologic
      symptoms that manifest with facial nerve paralysis are often thought to be due to
      a mastoid infection. Here is a report on a case of breast carcinoma presenting
      with otalgia, otorrhea, and facial paralysis for 2 months. The patient was
      initially diagnosed as mastoiditis, and later the clinical impression was revised
      to metastatic breast carcinoma to temporal bone, based on the pathologic
      findings. Metastatic disease should be considered as a possible etiology in
      patients with a clinical history of malignant neoplasms presenting with common
      otologic or vestibular symptoms, especially with facial nerve paralysis.

PMID- 15720076
TI  - Madelung's disease.
AB  - Madelung's disease is a rare disease of undetermined cause characterized by
      symmetric deposits of painless, diffuse, subcutaneous adipose tissue on the
      suboccipital area, the cheeks, the neck, the shoulders and the upper trunk. It is
      commonest in countries bordering the Mediterranean. The patients are usually
      middle-aged male alcoholics. Although lesions can initially mimic a head and neck
      malignancy, management is essentially symptomatic, with conservative removals
      done as indicated clinically or for cosmesis. Oriental reports about Madelung's
      disease are very rare. Here a case of Madelung's disease in a 59-year-old male is
      described. We describe his clinical course and review the literature.

PMID- 15720077
TI  - Biophoton imaging: a nondestructive method for assaying R gene responses.
AB  - Plant disease resistance (R) proteins of the nucleotide binding-leucine rich
      repeat class are responsible for pathogen recognition and activation of defense
      signaling networks leading to the hypersensitive response (HR). Genetically, R
      protein signaling appears to be integrated through a limited set of common
      downstream components. However, the timing of development of visible HR is unique
      to individual R proteins. By utilizing the phenomena of ultraweak photon emission
      from leaves undergoing an incompatible interacttion, a powerful nondestructive
      and facile assay is described to compare timing of defense responses elicited by
      different R proteins. We demonstrate that ultraweak photon emission, or
      "biophoton generation," is demonstrated to be associated with hypersensitive cell
      death. Biophoton emission requires an intact R signaling network and increases in
      cytosolic calcium and nitric oxide, but elevated reactive oxygen species are not
      necessary. Importantly, the assay is robust and applicable to a range of
      incompatible interactions in various plant species. The ability to assay R
      responses nondestructively in real time and a chosen genetic background makes
      this technique amenable to subtle genetic dissection of plant defense responses.

PMID- 15720078
TI  - Diversification of non-TIR class NB-LRR genes in relation to whole-genome
      duplication events in Arabidopsis.
AB  - Arabidopsis thaliana is believed to have experienced at least two and possibly
      three whole-genome duplication events in its evolutionary history. In order to
      investigate the evolutionary relationships between these duplication events and
      diversification of disease resistance (R) genes, segmental-duplication events
      containing R genes belonging to the nucleotide binding-leucine rich repeat (NB
      LRR) class were identified. Of 153 segmental-duplication events containing NB-LRR
      genes, only 22 contained NB-LRR genes in both members of the duplication pair,
      indicating a high frequency of NB-LRR gene loss after whole-genome duplication.
      The relative age of the duplication events was estimated based on the average
      synonymous substitution rate of the duplicated gene pairs in the segments. These
      data were combined with phylogenetic analyses. NB-LRR genes present in segment
      pairs derived from the most recent whole-genome duplication event, estimated to
      have occurred only 20 to 40 million years ago, occupy very distant branches of
      the NB-LRR phylogenetic tree. These data suggest that when NB-LRR clusters are
      duplicated as part of a whole-genome duplication, homoeologous NB-LRR genes are
      preferentially lost, either by eliminating one copy of the cluster or by
      eliminating individual genes such that only paralogous NB-LRR genes are
      maintained.

PMID- 15720079
TI  - Mannitol 1-phosphate metabolism is required for sporulation in planta of the
      wheat pathogen Stagonospora nodorum.
AB  - An expressed sequence tag encoding a putative mannitol 1-phosphate dehydrogenase
      (Mpd1) has been characterized from the fungal wheat pathogen Stagonospora
      nodorum. Mpd1 was disrupted by insertional mutagenesis, and the resulting mpd1
      strains lacked all detectable NAD-linked mannitol 1-phosphate dehydrogenase
      activity (EC 1.1.1.17). The growth rates, sporulation, and spore viability of the
      mutant strains in vitro were not significantly different from the wild type. The
      viability of the mpd1 spores when subjected to heat stress was comparable to wild
      type. Characterization of the sugar alcohol content by nuclear magnetic resonance
      spectroscopy revealed that, when grown on glucose, the mutant strains contained
      significantly less mannitol, less arabitol, but more trehalose than the wild-type
      strains. The mannitol content of fructose-grown cultures was normal. No secreted
      mannitol could be detected in wild type or mutants. Pathogenicity assays revealed
      the disruption of Mpd1 did not affect lesion development, however the mutants
      were unable to sporulate. These results throw new light on the role of mannitol
      in fungal plant interactions, suggesting a role in metabolic and redox regulation
      during the critical process of sporulation on senescing leaf material.

PMID- 15720081
TI  - Transcript profiles of Blumeria graminis development during infection reveal a
      cluster of genes that are potential virulence determinants.
AB  - High-density cDNA microarrays (2,027 unigenes) were used to analyze transcript
      profiles of the plant-pathogenic fungus Blumeria graminis f. sp. hordei
      throughout its asexual life cycle and development of infection. RNA was obtained
      from four stages preceding penetration and four stages after penetration of the
      host cells. The microarray data was validated by comparing the expression of a
      plasma membrane H+-ATPase and fructose-1,6-bis phosphatase with the data obtained
      from a quantitative polymerase chain reaction (PCR) assay. The results showed
      that there was a global switch in expression between the pre- and postpenetrative
      stages. This was largely due to accumulation of RNA encoding protein biosynthesis
      genes in the late stages. Other functional clusters, such as virulence-related
      genes and sterol metabolism genes, are up-regulated in pre- and postpenetration
      stages, respectively. A group of RNAs whose abundance correlated with the
      expression of cap20, a gene known to be required for virulence in Colletotrichum
      gloeosporioides, identified genes that are strong candidates for pathogenicity
      factors in B. graminis.

PMID- 15720080
TI  - Involvement of the small GTPase Rac in the defense responses of tobacco to
      pathogens.
AB  - During the hypersensitive response (HR), plants accumulate reactive oxygen
      species (ROS) that are likely generated at least in part by an NADPH oxidase
      similar to that found in mammalian neutrophils. An essential regulator of
      mammalian NADPH oxidase is the small GTP-binding protein Rac. To investigate
      whether Rac also regulates the pathogen-induced oxidative burst in plants, a
      dominant negative form of the rice OsRac1 gene was overexpressed in tobacco
      carrying the N resistance gene. Following infection with Tobacco mosaic virus
      (TMV), DN-OsRacl plants developed smaller lesions than wild-type plants,
      accumulated lower levels of lipid peroxidation products, and failed to activate
      expression of antioxidant genes. These results, combined with the demonstration
      that superoxide and hydrogen peroxide levels were reduced in DN-OsRacl tobacco
      developing a synchronous HR triggered by transient expression of the TMV p50
      helicase domain or the Pto and AvrPto proteins, suggest that ROS production is
      impaired. The dominant negative effect of DN-OsRacl could be rescued by
      transiently overexpressing the wild-type OsRac1 protein. TMV-induced salicylic
      acid accumulation also was compromised in DN-OsRacl tobacco. Interestingly, while
      systemic acquired resistance to TMV was not impaired, nonhost resistance to
      Pseudomonas syringae pv. maculicola ES4326 was suppressed. Thus, the effect DN
      OsRac1 expression exerts on the resistance signaling pathway appears to vary
      depending on the identity of the inoculated pathogen.

PMID- 15720082
TI  - Probing the Sinorhizobium meliloti-alfalfa symbiosis using temperature-sensitive
      and impaired-function citrate synthase mutants.
AB  - To study the role of the decarboxylating leg of the bacterial TCA cycle in
      symbiotic nitrogen fixation, we used DNA shuffling and localized random
      polymerase chain reaction mutagenesis to construct a series of temperature
      sensitive and impaired-function mutants in the Sinorhizobium meliloti Rm104A14
      citrate synthase (gltA) gene. Reducing citrate synthase (CS) activity by mutation
      led to a corresponding decrease in the free-living growth rate; however, alfalfa
      plants formed fully effective nodules when infected with mutants having CS
      activities as low as 7% of the wild-type strain. Mutants with approximately 3% of
      normal CS activity formed nodules with lower nitrogenase activity and a mutant
      with less than 0.5% of normal CS activity formed Fix- nodules. Two temperature
      sensitive (ts) mutants grew at a permissive temperature (25 degrees C) with 3% of
      wild-type CS activities but were unable to grow on minimal medium at 30 degrees
      C. Alfalfa plants that were inoculated with the ts mutants and grown with a root
      temperature of 20 degrees C formed functional nodules with nitrogenase activities
      approximately 20% of the wild type. When the roots of plants infected with the ts
      mutants were transferred to 30 degrees C, the nodules lost the ability to fix
      nitrogen over several days. Microscopic examination of these nodules revealed the
      loss of bacteroids and senescence, indicating that CS activity was essential for
      nodule maintenance.

PMID- 15720083
TI  - Avoidance of host recognition by alterations in the repetitive and C-terminal
      regions of AvrXa7, a type III effector of Xanthomonas oryzae pv. oryzae.
AB  - avrXa7 is a member of the avrBs3/pthA gene family. The gene is a critical type
      III effector in several strains of Xanthomonas oryzae pv. oryzae (virulence
      activity), and in the presence of the Xa7 host gene for resistance, controls the
      elicitation of resistance in rice (avirulence activity). The ability of strains
      containing avrXa7 to adapt to the presence of Xa7 in the host population is
      dependent, in part, on the genetic plasticity of avrXa7. The potential for the
      conversion of avrXa7 to a virulence effector without Xa7-dependent elicitor
      activity was examined. Internal reorganization of avrXa7 by artificially deleting
      a portion of the central repetitive region resulted in gene pthXo4, which
      retained virulence activity and lost Xa7-dependent avirulence activity.
      Similarly, spontaneous rearrangements between repetitive regions of avrXa7 during
      bacterial culture gave rise to gene pthXo5, which also had virulence activity
      without Xa7-dependent avirulence activity. pthXo5 appeared to be the result of
      recombination between avrXa7 and a related gene in the genome. Loss of avirulence
      activity and retention of virulence activity also resulted from replacement of a
      portion of the C-terminal coding region of avrXa7 with the corresponding sequence
      from avrBs3. The results demonstrated the potential for a critical virulence
      effector to lose avirulence activity while retaining effector function. The
      results also demonstrated that features of both repetitive and nonrepetitive C
      terminal regions of AvrXa7 are involved in avirulence specificity.

PMID- 15720084
TI  - Mutations of ousA alter the virulence of Erwinia chrysanthemi.
AB  - A negative correlation was observed between the aggressiveness of several Erwinia
      chrysanthemi strains on potato tuber and their osmotic tolerance. The disruption
      of the ousA gene encoding the major osmoprotectant uptake system highly enhanced
      bacterial virulence on potato tubers. The ousA disruption also increased the
      maceration efficiency on potato tubers under anaerobic conditions. In the absence
      of oxygen, pectate lyase (Pel) production was significantly higher in the tissue
      macerated with the ousA- strain than with the wild type. Oxygen content is
      significantly different between infected and healthy tissues; therefore, ousA may
      be a contributory factor in the infection progression within the host. In minimal
      medium, ousA disruption enhanced Pel production and pelE expression only under
      micro-aerobiosis conditions. The effect on Pel was reversed by reintroduction of
      the ousA gene. The osmoprotectectants glycine betaine, proline betaine, and
      pipecolic acid are known to be taken up via OusA and to have an inhibitory effect
      on Pel production. However, their effects on Pel activity were not (glycine
      betaine) or only weakly (proline and pipecolic acid) affected by ousA disruption.
      Furthermore, no correlation was observed between their effects on Pel activities
      and their osmoprotection efficacies. The results demonstrate a relationship
      between E. chrysanthemi pathogenicity factors and the activity of ousA under low
      oxygen status. The evidence indicates that ousA and osmoprotectant effects on Pel
      are not linked to osmoregulation and that complex regulations exist between Pel
      production, ousA, and osmoprotection via compounds liberated during the plant
      infection.

PMID- 15720085
TI  - Characterization of susceptibility and resistance responses to potato cyst
      nematode (Globodera spp.) infection of tomato lines in the absence and presence
      of the broad-spectrum nematode resistance Hero gene.
AB  - The tomato Hero A gene is the only member of a multigene family that confers a
      high level (>80%) of resistance to all the economically important pathotypes of
      potato cyst nematode (PCN) species Globodera rostochiensis and G. pallida.
      Although the resistance levels of transgenic tomato lines were similar to those
      of the tomato line LA1792 containing the introgressed Hero multigene family,
      transgenic potato plants expressing the tomato Hero A gene are not resistant to
      PCNs. Comparative microscopy studies of in vitro infected roots of PCN
      susceptible tomato cv. Money Maker, the resistant breeding line LA1792, and
      transgenic line L10 with Ro1 pathotype have revealed no statistically significant
      difference in the number of juveniles invading roots. However, syncytia
      (specialized feeding cells) induced in LA1792 and L10 roots mostly were found to
      have degenerated a few days after their induction, and a few surviving syncytia
      were able to support only the development of males rather than females. Thus, the
      ratio between males and females was biased towards males on LA1792 and L10 roots.
      A series of changes occur in resistant plants leading to formation of a layer of
      necrotic cells separating the syncytium from stellar conductive tissues and this
      is followed by degradation of the syncytium. Although the Hero A gene is
      expressed in all tissues, including roots, stems, leaves, and flower buds, its
      expression is upregulated in roots in response to PCN infection. Moreover, the
      expression profiles of the Hero A correlates with the timing of death of the
      syncytium.

PMID- 15720086
TI  - Regulation of enteric endophytic bacterial colonization by plant defenses.
AB  - Bacterial endophytes reside within the interior of plants without causing disease
      or forming symbiotic structures. Some endophytes, such as Klebsiella pneumoniae
      342 (Kp342), enhance plant growth and nutrition. Others, such as Salmonella
      enterica serovar Typhimurium (S. typhimurium), are human pathogens that
      contaminate raw produce. Several lines of evidence are presented here to support
      the hypothesis that plant defense response pathways regulate colonization by
      endophytic bacteria. An ethylene-insensitive mutant of Medicago truncatula is
      hypercolonized by Kp342 compared to the parent genotype. Addition of ethylene, a
      signal molecule for induced systemic resistance in plants, decreased endophytic
      colonization in Medicago spp. This ethylene-mediated inhibition of endophytic
      colonization was reversed by addition of the ethylene action inhibitor, 1
      methylcyclopropene. Colonization of Medicago spp. by S. typhimurium also was
      affected by exogenous ethylene. Mutants lacking flagella or a component of the
      type III secretion system of Salmonella pathogenicity island 1 (TTSS-SPI1)
      colonize the interior of Medicago spp. in higher numbers than the wild type.
      Arabidopsis defense response-related genotypes indicated that only salicylic acid
      (SA)-independent defense responses contribute to restricting colonization by
      Kp342. In contrast, colonization by S. typhimurium is affected by both SA
      dependent and -independent responses. S. typhimurium mutants further delineated
      these responses, suggesting that both flagella and TTSS-SPI1 effectors can be
      recognized. Flagella act primarily through SA-independent responses (compromising
      SA accumulation still affected colonization in the absence of flagella). Removal
      of a TTSS-SPI1 effector resulted in hypercolonization regardless of whether the
      genotype was affected in either SA-dependent or SA-independent responses.
      Consistent with these results, S. typhimurium activates the promoter of PR1, a SA
      dependent pathogenesis-related gene, while S. typhimurium mutants lacking the
      TTSS-SPI1 failed to activate this promoter. These observations suggest approaches
      to reduce contamination of raw produce by human enteric pathogens and to increase
      the number of growth-promoting bacteria in plants.

PMID- 15720087
TI  - Multicenter study of the safety and efficacy of a 585 nm pulsed-dye laser for the
      nonablative treatment of facial rhytides.
AB  - OBJECTIVE: The objective of this study was to assess the safety and efficacy of a
      585 nm flashlamp pulsed-dye laser for the nonablative treatment of facial
      rhytides. METHODS: A multicenter prospective randomized controlled study on 58
      volunteers was performed. A split-face approach was adopted, with one periorbital
      region acting as a control and the other receiving either one or two treatments.
      Patients were photographed and imaged three-dimensionally before and after
      treatment. Histologic sections were analyzed. RESULTS: Three-dimensional
      topographic evaluation showed improvements of 9.8% (p = .0022) and 15% (p =
      .0029) in surface roughness for single and double treatments, respectively.
      Histology revealed an increase in type I collagen messenger ribonucleic acid
      expression, type III procollagen, chondroitin sulfate, and grenz zone thickness.
      Two treatments resulted in greater improvement than one treatment. CONCLUSION:
      Clinical improvement was achieved following a single treatment. Further
      improvement was observed following a second treatment. The subjective evaluation
      of clinical improvement was consistent with both histologic and topographic
      quantitative measurements.

PMID- 15720088
TI  - Curettage prior to Mohs' micrographic surgery for previously biopsied nonmelanoma
      skin cancers: what are we curetting? Retrospective, prospective, and comparative
      study.
AB  - BACKGROUND: Curettage prior to excision and Mohs' micrographic surgery for
      nonmelanoma skin cancer is performed based on the assumption that the curette
      will remove softer, more friable tumor-infiltrated dermis and leave structurally
      intact normal skin. This assumption, however, has not been objectively examined
      in the dermatologic surgery literature. OBJECTIVE: We performed a study to
      examine the ability of curettage to selectively remove and delineate nonmelanoma
      skin cancer prior to Mohs' micrographic surgery. METHODS: The study included 150
      previously biopsied basal cell and squamous cell carcinomas less than 1.5 cm in
      size. We conducted (1) a retrospective study of 50 tumors curetted prior to Mohs'
      surgery by a surgeon who routinely curettes preoperatively; (2) a prospective
      study in which a surgeon who routinely does not curette preoperatively curetted
      50 tumors prior to Mohs' surgery; and (3) a comparative historical group of 50
      noncuretted tumors treated with Mohs' surgery by the latter surgeon. All curetted
      tissue was evaluated histologically. RESULTS: Only 50% of the curetted tissue
      demonstrated the presence of tumor in the curettings, but in 76% of these, the
      curette left residual tumor at the surgical margins. Of the other 50% in which
      the curette removed only non-cancer-containing skin, 34% had tumor present at the
      surgical margin. Overall, the curette removed tumor, leaving no residual tumor at
      the surgical margins in only 12% of lesions. Comparison with historical
      noncuretted tumors operated on by the same surgeon showed that curettage did not
      affect the mean number of stages or the proportion of tumors requiring more than
      one stage for histologic clearance. CONCLUSION: Although curettage may be helpful
      in debulking friable skin prior to Mohs' micrographic surgery, it does not
      reliably delineate the extent of a tumor.

PMID- 15720089
TI  - Candida antigen in the treatment of basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer. Recently,
      there has been renewed interest in various immunotherapies in the treatment of
      BCC. The current study is a randomized, open-label, placebo-controlled trial of
      intralesional Candida antigen in the treatment of nodular BCC. OBJECTIVE: The
      objective of this study was to evaluate the safety and efficacy of intralesional
      Candida antigen in the treatment of BCC. RESULTS: In the control group, no
      patients had complete clearing of their tumor. In the Candida group, 10 of 17
      (56%) patients had complete clearing of their tumor. The Fisher exact test was
      used to compare the two treatment groups. This showed the difference in clearance
      rates to be of borderline significance, with a p value of .105. CONCLUSION:
      Although immunotherapy with repeated injections of Candida antigen appears to be
      effective in clearing superficial and nodular BCCs, it is unlikely to alter our
      current treatment of BCC.

PMID- 15720090
TI  - Stability of foam in sclerotherapy: differences between sodium tetradecyl sulfate
      and polidocanol and the type of connector used in the double-syringe system
      technique.
AB  - BACKGROUND: Foam sclerotherapy is an increasingly popular modality in the
      treatment of varicose veins. Worldwide, the most popular agents used are sodium
      tetradecyl sulfate (STS) and polidocanol (POL). The double-syringe system
      technique to make foam out of a sclerosing solution and air has received wide
      attention for its ease and reproducibility. This study examined the possibility
      that the relative silicone content of various disposable connectors may affect
      overall foam stability. We also evaluated the differences in the stability of
      foam between STS and POL. MATERIALS AND METHODS: In the first part of the study,
      one nondisposable stainless steel connector and five disposable plastic
      connectors were used to create foam from STS 0.50% and air. The procedure was
      then repeated to produce foam from POL 0.50% and air from each of the six
      different connector types. As a measure of foam stability, once foam was created
      with each type of connector, the time required for half of the original volume of
      sclerosing solution to settle was recorded. In the second part of the study, foam
      was created with a nondisposable stainless steel connector only and various
      concentrations of STS and POL. Foam stability was then measured for these
      different concentrations of sclerosants. RESULTS: The time for sclerosing
      solution to settle to half of its initial volume was found to vary according to
      the specific sclerosant and concentration used, with no statistically significant
      variation based on connector type. CONCLUSIONS: The type of connector used in the
      double-syringe system technique to produce foam for sclerotherapy is not a factor
      in foam stability. Sclerosing solutions differ in their foaming stability.

PMID- 15720091
TI  - How long can hair follicle units be preserved at 0 and 4 degrees C for delayed
      transplant?
AB  - BACKGROUND: Preservation of hair follicle units for the purpose of delayed
      transplant will help us graft thousands of hair grafts at one session, even in a
      clinic with fewer assistants and less equipment. OBJECTIVE: This study was
      undertaken to evaluate and compare the viability of hair follicle units preserved
      at 0 and 4 degrees C for various periods. MATERIALS AND METHODS: Cell cultures
      and transplant of hair follicle units into athymic mice were performed. RESULTS:
      Outer root sheath cells could be cultivated in 96% (0 degrees C group) and 92% (4
      degrees C group) of the hair follicles after 24 hours of preservation, whereas
      85% (0 degrees C group) and 79% (4 degrees C group) of the follicles implanted
      into the mice regrew well after the same period of preservation. Then, in both
      the 0 degrees C and the 4 degrees C group, these rates decreased significantly
      with length of preservation in cell cultures and mice transplant; however, 0
      degrees C seems better than 4 degrees C for preservation of grafts (p<.05).
      CONCLUSION: Grafts are better preserved at 0 degrees C instead of 4 degrees C.
      When delayed transplant is an option, it should be completed within 24 hours and
      no later than 48 hours.

PMID- 15720092
TI  - Dermatologic surgery practice and skin cancer treatment in Canada: results of a
      national survey.
AB  - BACKGROUND: Although traditionally considered a medical subspecialty, dermatology
      has rapidly evolved over the past two decades to encompass a wide variety of
      cutaneous surgical procedures. OBJECTIVE: The study was carried out to evaluate
      the status of dermatologic surgery practice and skin cancer treatment in Canada.
      METHODS: In 2003, 550 practicing Canadian dermatologists were surveyed. RESULTS:
      Two hundred fifty-one dermatologists responded to the questionnaire, with the
      majority practicing in an urban part-time academic, part-time private setting.
      Statistics are presented on the types and demographics of dermatosurgical and
      cosmetic procedures performed, as well as on the specific dermatosurgical
      therapies used in the treatment of various cutaneous malignancies. CONCLUSIONS:
      The survey provides a current picture of dermatologic surgery practice and skin
      cancer treatment in Canada. The data suggest that Canadian dermatologists are
      further embracing surgical and cosmetic procedures.

PMID- 15720093
TI  - Topical photodynamic therapy using intense pulsed light for treatment of actinic
      keratosis: clinical and histopathologic evaluation.
AB  - BACKGROUND: Photodynamic therapy (PDT) is suitable for the treatment of actinic
      keratosis, and, recently, topical PDT using intense pulsed light as a light
      source has been reported. However, evaluations of its therapeutic effects have
      been clinically based. OBJECTIVE: The objective of this study was to confirm the
      histopathologic resolution of actinic keratosis treated by topical PDT using
      intense pulsed light as a light source. METHODS: Twelve actinic keratosis lesions
      in seven patients were treated with 5-aminolevulinic acid-PDT using intense
      pulsed light as a light source. After a single treatment, the clinical response
      was assessed and histopathologic examinations were performed on clinically
      resolved lesions. RESULTS: Six of 12 (50%) lesions showed clinical clearance
      after a single treatment, but histologic examinations showed that only 5 of the
      12 (42%) lesions had been removed. No complications, such as pigmentary changes
      or scarring, were observed. CONCLUSION: Intense pulsed light is potentially an
      effective light source for PDT. However, the determination of complete remission
      in actinic keratosis requires caution, and long-term follow-up or histologic
      confirmation may be required.

PMID- 15720094
TI  - High recurrence rates of squamous cell carcinoma after Mohs' surgery in patients
      with chronic lymphocytic leukemia.
AB  - BACKGROUND: Cutaneous cancers exhibit a much higher incidence in patients with
      chronic lymphocytic leukemia than in nonleukemic patients. Squamous and basal
      cell carcinomas also exhibit greater subclinical tumor extension in patients with
      chronic lymphocytic leukemia. OBJECTIVE: The purpose of this study was to
      estimate and compare the recurrence rates of squamous cell carcinoma after Mohs'
      surgery in patients with chronic lymphocytic leukemia compared with those in
      controls and to evaluate differences among squamous cell carcinoma size and
      histologic grade. METHODS: We retrospectively assessed the clinical histories,
      postoperative notes, and surgical photographs of patients with chronic
      lymphocytic leukemia and controls matched (2:1) for age, sex, and surgical year.
      Both patients and controls underwent Mohs' surgery for squamous cell carcinoma of
      the head and neck at the Mayo Clinic between March 1988 and April 1999. RESULTS:
      Twenty-eight patients who underwent Mohs' surgery for 57 squamous cell carcinomas
      had 7 recurrences. The cumulative incidence of recurrence on a per-tumor basis
      was 4.3% at 1 year, 14.8% at 3 years, and 19.0% at 5 years. Squamous cell
      carcinoma was seven times more likely to recur in patients with chronic
      lymphocytic leukemia than in controls (p = .003). The distribution of tumor
      histologic grade was not significantly different between patients and controls (p
      = .39). Maximum preoperative tumor diameters were clinically similar between
      patients and controls (median 15 mm vs 14 mm; p = .04). CONCLUSION: The
      recurrence rates of squamous cell carcinoma were significantly higher in patients
      with chronic lymphocytic leukemia. Squamous cell carcinomas in patients with
      chronic lymphocytic leukemia did not exhibit a significant difference in
      histologic grade or clinical difference in preoperative tumor size. Close
      surveillance for squamous cell carcinoma recurrence is warranted in patients with
      chronic lymphocytic leukemia.

PMID- 15720095
TI  - Clinical diagnosis of actinic keratosis identifies an elderly population at high
      risk of developing skin cancer.
AB  - BACKGROUND: Development of actinic keratoses (AK) involves some of the same
      processes as nonmelanoma skin cancer and may serve as a marker for overall
      increased risk of skin cancer. OBJECTIVE: The objective of this study was to
      examine the risk of developing skin cancer in an elderly population with and
      without AK. METHODS: This was a retrospective observational study. Data from the
      1992-1998 Medicare Current Beneficiary Study were used in the analyses. RESULTS:
      Multivariate analysis showed that the risk (odds ratio [OR]) of developing
      nonmelanoma or melanoma was increased more than sixfold (p < or = .0001) in
      patients with AK. An increased risk of skin cancer was found in whites (OR 4.3; p
      < or = .01) and increased age by year (OR 1.04; p < or = .01). Women were less
      likely to develop skin cancer (OR 0.58; p < or = .01). CONCLUSION: Using data
      from a nationally representive sample of the Medicare population, this study
      demonstrates that elders with AK are a population at high risk of developing
      cutaneous cancer.

PMID- 15720096
TI  - Objective assessment of burn scar vascularity, erythema, pliability, thickness,
      and planimetry.
AB  - BACKGROUND: There is currently a lack of objective methods to assess scars.
      OBJECTIVES: The objectives of this study were to (1) determine the pattern of
      scar formation up to 24 months after a burn, compare clinical and photographic
      scar assessment, and determine what percentage of scars became hypertrophic after
      a major trauma and (2) replace each clinical parameter of a clinical scar scale
      by objective measurements. METHODS: Scars from 62 patients were evaluated from
      the acute phase up to 24 months after the burn, using photographs and clinical
      assessment during visits. Photographic planimetry helped estimate the percentage
      of scars that became hypertrophic. Thereafter, 69 patients had scars evaluated
      using clinical assessment and several instruments to evaluate pigmentation,
      erythema, pliability, thickness, and perfusion. The sensitivity and specificity
      of each instrument were determined regarding their ability to correlate with the
      parameters of hypertrophic and nonhypertrophic scars. Analysis of variance and
      Tukey's test were used in statistical analysis, with p<.05 indicating
      significance. RESULTS: Increased scar hypertrophy occurred between 6 and 12
      months after the burn, and less than 30% of scars were hypertrophic at 18 to 24
      months. Objective assessment of pliability and erythema, but not pigmentation,
      correlated significantly with clinical evaluation of hypertrophy. Hypertrophic
      scars had significantly higher perfusion than nonhypertrophic scars. A new scar
      rating system is proposed, based on the sensitivity and specificity of each
      instrument, to correlate with hypertrophic and nonhypertrophic scars.
      CONCLUSIONS: Objective rating systems using reliable instruments can be used to
      replace subjective scar assessment. Larger multicenter prospective studies should
      test this new scale in scars due to other mechanisms of injury.

PMID- 15720097
TI  - Minimal-scar segmental extraction of lipomas: study of 122 consecutive
      procedures.
AB  - BACKGROUND: Surgical extirpation of lipomas that occur in cosmetically
      conspicuous areas of the body leaves a visible scar that is usually disfiguring.
      Minimal-scar segmental extraction (MSE) employs a much smaller incision and
      extraction and is particularly useful in exposed parts of the body. It can be
      easily performed in an office setting. OBJECTIVE: The objective of this study was
      to evaluate the merits of MSE in clinical practice. Unlike other reports in the
      literature that describe, anecdotally, minimally invasive methods of lipoma
      removal, our study examined a new method by carefully measuring the results in a
      larger group of consecutive patients treated using this technique. MATERIALS AND
      METHODS: A retrospective study was performed using data from 91 consecutive
      patients with a total of 122 lipomas that were treated using MSE. MSE of lipomas
      consists of a small stab incision and blind dissection of the tumor followed by
      its extraction in a segmental fashion. This procedure involves small
      instrumentation, minimal dissection with preservation of contour, and complete
      removal of the lipoma, including substantial portions of the capsule. Clinical
      data, including complications, outcomes, and recurrence rates, were recorded.
      RESULTS: The procedure was well tolerated by patients, who were pleased with the
      results, particularly the small scar. The incidence of complications was 1.6% (n
      = 2) and consisted of hematoma (n = 1) and seroma (n = 1). The recurrence rate
      was 0.8% (n = 1). No long-term morbidity was noted. CONCLUSIONS: The technical
      ease with which the MSE can be performed, coupled with a low recurrence rate,
      makes it a very cost-effective operation. The smaller postoperative scars, rapid
      healing, and low morbidity allow for better patient acceptance. We recognize the
      advantages and limitations of this procedure and encourage its use in selected
      patients.

PMID- 15720098
TI  - Upper eyelid full-thickness skin graft in facial reconstruction.
AB  - BACKGROUND: The potentially available upper eyelid skin, as an alternative donor
      site, deserves more attention in clinical use. OBJECTIVE: The objective of this
      study was to prospectively evaluate the clinical behavioral characteristics of
      upper eyelid full-thickness skin grafts in facial reconstruction. METHODS:
      Sixteen patients who concluded the 12-month follow-up period were included in the
      study. Graft dimensions were measured in place before the graft harvest. Defect
      sizes were measured following lesion excision and postgrafting. Graft sizes were
      measured postoperatively at 1, 3, 6, and 12 months. RESULTS: The largest and
      smallest grafts were 46 x 22 mm and 40 x 15 mm (average 43.1 x 19.3 mm) in size,
      respectively. The largest and smallest defect dimensions were 33 x 23 mm and 17 x
      9 mm (average 22.6 x 15.6 mm), respectively. The average postgrafting size was
      21.1 x 14.6 mm. Grafts and donor sites healed very well. Generally, an acceptable
      to good texture and color match was observed beyond 6 months. Wound bed
      contraction was not observed beyond the first month (p<.05). CONCLUSION: Special
      characteristics of hairless skin, good color and texture matching, and
      inconspicuous and hidden donor scar make the upper eyelid a good alternative
      donor site for small- to medium-sized facial skin defects. The main disadvantages
      that limit its clinical use are the age of the patient, a lack of adnexal
      structures, comparatively limited sun exposure, and possible insufficient
      thickness, especially when deep defects are of concern.

PMID- 15720099
TI  - Photodynamic therapy: new treatment for therapy-resistant plantar warts.
AB  - BACKGROUND: Plantar wart treatment remains a challenging one. Various treatment
      modalities have been previously used and are still in current use. The problem
      remains in the degree of response to these treatments and the side effects
      associated with them. OBJECTIVE: The aim of this study was to test a new
      treatment modality for therapy-resistant plantar warts. METHODS: Thirty-one
      patients with 48 plantar warts were randomly selected from the Department of
      Laser Therapy, Medical Centre Maastricht, The Netherlands. The mean age of the
      patients was 29 years (range 6-74 years). The mean incubation time was 6.8 hours,
      and the mean treatment time was 18.7 minutes per wart. Each wart was treated an
      average of 2.3 times, with a median fluence of 100 cm2. RESULTS: Forty-two of 48
      (88%) warts showed a complete response. A trend was found between total clearance
      and size of the warts, age of the patient, and the mean treatment time. No
      significant side effects were seen postoperatively. CONCLUSION: This study showed
      that recalcitrant plantar warts were successfully treated with no significant
      side effects; however, the user needs sufficient experience for this new
      effective treatment application.

PMID- 15720100
TI  - Skin cancer and non-Hodgkin's lymphoma: examining the link.
AB  - BACKGROUND: The incidence rates of melanoma and non-Hodgkin's lymphoma (NHL) have
      increased substantially worldwide over the past several decades. It has been
      hypothesized that ultraviolet light exposure through sunlight may be a common
      environmental risk factor shared by both skin cancer and NHL. OBJECTIVE: The
      purpose of this study was to better understand the association between skin
      cancer and NHL and to evaluate its implication in clinical practice. METHODS: We
      reviewed the current literature on the link between the two malignancies and on
      the role of ultraviolet light in the development of NHL. Publications were
      selected using a PUBMED search with the terms "non-Hodgkin's lymphoma" and "skin
      cancer." Epidemiologic studies in English and published after 1995 were the
      focus. CONCLUSIONS: Large population-based studies support an increased risk of
      subsequent NHL among patients with skin cancers (both melanoma and nonmelanoma
      skin cancers) and a risk of skin cancer development in patients with NHL,
      although support for a direct relationship between ultraviolet light and the
      incidence of NHL is weak and inconsistent. Given their increased risk of
      developing skin cancers, patients with a history of NHL may benefit from a full
      body examination during their visits.

PMID- 15720101
TI  - Antibiotic prophylaxis in dermatologic surgery: updated guidelines.
AB  - BACKGROUND: Antibiotic prophylaxis in dermatologic surgery is poorly understood,
      and data on its use are lacking. Prophylaxis is indicated for the prevention of
      endocarditis and prosthesis infection, as well as surgical site infection.
      OBJECTIVE: We review essential considerations for the use of antibiotic
      prophylaxis in dermatologic surgery and provide clear guidelines for practical
      implementation. METHODS: Guidelines were developed after review of the literature
      and consultation with infectious disease specialists and subspecialists in the
      areas of cardiac, orthopedic, and neurosurgical infectious disease at Mayo
      Clinic. RESULTS: Three factors affect the decision to use prophylactic
      antibiotics in dermatologic surgery: (1) the underlying indication for
      prophylaxis (patient risk stratification), (2) the condition of the skin, and (3)
      the specific procedure planned. Thorough preoperative evaluation and surgical
      planning are critical in identifying and optimizing patient and environmental
      risk factors that may increase the risk of infection. Appropriate antibiotic
      selections with site-specific consideration and appropriate timing of antibiotic
      administration are key factors in providing effective prophylaxis. CONCLUSIONS:
      Low rates of infection associated with dermatologic surgical procedures warrant
      selective use of antibiotic prophylaxis. The proposed guidelines reflect current
      standards of practice.

PMID- 15720102
TI  - Antibiotic prophylaxis in dermatologic surgery: updated guidelines. Counterpoint.

PMID- 15720103
TI  - A splint for pincer nail surgery: a convenient splinting device made of an
      aspiration tube.
AB  - BACKGROUND: To treat pincer nail, both conservative therapy and surgical therapy
      have been reported. However, there is no consensus about the best method of
      treatment. OBJECTIVE: The use of a splint prepared from an aspiration tube after
      pincer nail surgery is introduced. METHODS: Pincer nail was treated by surgery
      with splinting in seven patients (nine toes). RESULTS: Nine toes from seven
      patients were evaluated. The postoperative follow-up period ranged from 6 to 37
      months (mean 17.7 months). An excellent result was obtained in eight toes, but
      ingrowth of the nail occurred in one toe. The cosmetic improvement was marked and
      satisfactory. CONCLUSION: This splint is cheap and easy to make, can prevent
      contracture of the nail matrix and nail bed, can reduce pain, and allows direct
      observation of the nail bed because it is transparent. Thus, this technique seems
      to be convenient and useful.

PMID- 15720104
TI  - Reconstruction of the superior helical rim with a postauricular transposition
      flap.

PMID- 15720105
TI  - Clinical and dermoscopic image of an intermediate stage of regressing seborrheic
      keratosis in a lichenoid keratosis.

PMID- 15720106
TI  - Use of hyaluronic acid for soft tissue augmentation of HIV-associated facial
      lipodystrophy.
AB  - BACKGROUND: Lipodystrophy syndrome is a devastating complication of
      antiretroviral therapy in individuals with human immunodeficiency virus (HIV).
      The appearance of the associated facial lipoatrophy can be demoralizing and
      stigmatizing for the affected individuals to a point at which it may compromise
      their compliance with antiretroviral medication. OBJECTIVE: We describe the use
      of hyaluronic acid as an intradermal filler for correction of this disfiguring
      problem. METHODS: We treated five patients with grade 2 to 3 facial lipoatrophy.
      Each patient received approximately 5 to 6 cc in total of hyaluronic acid in the
      malar area via intradermal injection. RESULTS: There were no adverse events. We
      found that this technique provided a good cosmetic result with high patient
      satisfaction. At 6-month follow-up, sustained longevity was observed.
      CONCLUSIONS: We propose the use of hyaluronic acid for HIV-associated facial
      lipoatrophy as an efficacious and safe, but temporary, option for this problem
      until a more cost-effective option is available.

PMID- 15720107
TI  - Guiding sutures to promote optimal contraction of a large surgical defect prior
      to delayed grafting.
AB  - BACKGROUND: Large surgical defects on the face are often challenging to repair.
      OBJECTIVE: To describe a method to reduce wound area and promote wound
      contraction. MATERIALS AND METHODS: Case report. Mohs' excision of a neglected
      basal cell carcinoma on the cheek left a large defect of 54 cm2. Delayed grafting
      was selected for the repair due to the size of the wound and the presence of
      multiple foci of perineural, muscle and parotid invasion. Two 4-0 polyglactin
      guiding sutures were placed across the inferior half of the wound; the superior
      half of the wound was allowed to granulate. RESULTS: At the time of split
      thickness skin grafting 17 days later, the entire wound was 42% smaller than the
      original defect. The superior half of the wound was reduced by 29%, attributable
      to granulation. The inferior half of the wound was reduced by 55%, attributable
      to granulation and the contractile effect of guiding sutures. CONCLUSIONS: The
      placement of guiding sutures across large defects is a quick and simple technique
      that promotes optimal wound contraction with substantial reduction in the size of
      a wound, improving the final surgical result.

PMID- 15720108
TI  - Excision of malignant melanoma overlying a pacemaker.
AB  - BACKGROUND: With the increasing number of patients with implantable cardiac
      devices, dermatologic surgeons must be increasingly familiar with the types of
      devices and potential interference by surgical procedures. OBSERVATIONS: We
      report the excision of a 1 cm malignant melanoma in situ occurring on the skin
      directly overlying the patient's pacemaker. CONCLUSIONS: Successful excision of
      malignant lesions in the setting of implantable cardiac devices requires an
      understanding of pacemaker implantation anatomy following well-established
      guidelines for electrosurgery in the setting of implantable cardiac devices and
      careful coordination with cardiac and anesthesia specialists.

PMID- 15720109
TI  - Dermatofibrosarcoma protuberans of the forehead and scalp with involvement of the
      outer calvarial plate: multistaged repair with the use of skin expanders.
AB  - BACKGROUND AND OBJECTIVE: Dermatofibrosarcoma protuberans (DFSP) is a locally
      aggressive and infiltrative tumor that requires Mohs' micrographic surgery or
      wide excision to treat. Adequate excision often leaves a cosmetic disfiguring
      defect, particularly if the tumor is located on the head and neck. Complex
      defects of the face present special problems, such as distortion, ectropion, and
      retraction of normal tissues. PATIENT AND METHODS: We present a case of an
      infiltrating DFSP of the forehead and scalp in a young woman. The tumor was
      removed, and the defect was reconstructed with multistaged repair, which included
      bone coverage, local and regional flaps, and the use of expanders. RESULTS: A
      multistaged repair was performed with good clinical outcome and satisfactory
      cosmetic results. CONCLUSION: Multistaged repair of the face is a viable
      alternative surgical approach to preserve facial contours and minimize distortion
      in the treatment of DFSP. This case illustrates the degree of complexity that the
      treatment of DFSP may involve.

PMID- 15720110
TI  - Re: Differentiating vessels from globules on dermoscopy.

PMID- 15720111
TI  - Re: Abrasive procedures and basal cell nevus syndrome.

PMID- 15720112
TI  - Cytochrome P450 enzymes as catalysts of metabolism of 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone, a tobacco specific carcinogen.

PMID- 15720113
TI  - Amino effect on the protonation of beta-aminoacrylonitrile.
AB  - The protonation of acrylonitrile (1) and of Z- and E-3-aminoacrylonitrile (5 and
      9) was studied with the Gaussian-2 method. Ammoniumacrylonitrile ion formation is
      not important. Nitrilium ion formation is preferred in all cases, and the proton
      affinities are about 80 kJ/mol higher for aminoacrylonitrile. Remarkably, it is
      found that C2-protonation of 3-aminoacrylonitriles to form iminium ions can
      compete with nitrilium ion formation. Beta-aminoacrylonitriles thus show
      propinquity to both acrylonitriles and enamines, and mechanistic and
      toxicological implications are discussed.

PMID- 15720114
TI  - Integrated metabonomic analysis of the multiorgan effects of hydrazine toxicity
      in the rat.
AB  - Hydrazine is a model toxin that induces both hepatotoxic and neurotoxic effects
      in experimental animals. The direct biochemical effects of hydrazine in kidney,
      liver, and brain tissue were assessed in male Sprague-Dawley rats using magic
      angle spinning nuclear magnetic resonance (NMR) spectroscopy. A single dose of
      hydrazine (90 mg/kg) resulted in changes to the biochemical composition of the
      liver after 24 h including an increase in triglycerides and beta-alanine,
      together with a decrease in hepatic glycogen, glucose, choline, taurine, and
      trimethylamine-N-oxide (TMAO). From histopathology measurements of liver tissue,
      minimal to mild hepatocyte alteration was observed in all animals at 24 h. The
      NMR spectra of the renal cortex at 24 h after dosing were dominated by a marked
      increase in the tissue concentration of 2-aminoadipate (2-AA) and beta-alanine,
      concomitant with depletions in TMAO, myo-inositol, choline, taurine, glutamate,
      and lysine. No alteration to the NMR spectral profile of the substantia nigra was
      observed after hydrazine administration, but perturbations to the relative
      concentrations of creatine, aspartate, myo-inositol, and N-acetyl aspartate were
      apparent in the hippocampus of hydrazine-treated animals at 24 h postdose. No
      overt signs of histopathological toxicity were observed in either the kidney or
      the brain regions examined. Elevated alanine levels were observed in all tissues
      indicative of a general inhibition of alanine transaminase activity. By 168 h
      postdose, NMR spectral profiles of treated rats appeared similar to those of
      matched controls for all tissue types indicative of recovery from toxic insult.

PMID- 15720115
TI  - Nuclear magnetic resonance analysis of indomethacin-induced gastric ulcers.
AB  - Acetonitrile extracts of ulcerated and control rat stomachs were studied by
      various NMR techniques in an attempt to understand how indomethacin, a common and
      powerful nonsteroidal antiinflammatory drug (NSAID), induces ulcers in the
      stomach. One- (1D) and two-dimensional (2D) NMR spectra of extracts of ulcerated
      and control stomachs revealed that glycolytic and Krebs cycle enzymes were
      partially inhibited in the ulcerated stomach as shown by the lactate/glucose
      ratio. The (total choline)/lactate ratio was also higher in the extract from the
      control stomach than in the ulcerated stomach. Glycerophosphoethanolamine and
      glycerophosphocholine concentrations were higher in the ulcerated stomach extract
      as compared with the control stomach extract. These results explain the
      gastrointestinal protective effect of D-glucose and Krebs cycle intermediates on
      NSAID-induced ulceration.

PMID- 15720116
TI  - Photodecomposition of retinyl palmitate in ethanol by UVA light-formation of
      photodecomposition products, reactive oxygen species, and lipid peroxides.
AB  - Photodecomposition of retinyl palmitate (RP), an ester and the storage form of
      vitamin A (retinol), in ethanol under UVA light irradiation was studied. The
      resulting photodecomposition products were separated by reversed-phase HPLC and
      identified by spectral analysis and comparison with the chromatographic and
      spectral properties of synthetically prepared standards. The identified products
      include 5,6-epoxy-RP, 4-keto-RP, 11-ethoxy-12-hydroxy-RP, 13-ethoxy-14-hydroxy
      RP, anhydroretinol (AR), palmitic acid, ethyl palmitate, and four tentatively
      assigned cis and trans isomeric 15-ethoxy-ARs. AR was formed as a mixture of all
      trans-AR, 6Z-cis-AR, 8Z-cis-AR, and 12Z-cis-AR with all-trans-AR predominating.
      5,6-Epoxy-RP, 4-keto-RP, 11-ethoxy-12-hydroxy-RP, and 13-ethoxy-14-hydroxy-RP
      were also formed from reaction of RP with alkylperoxy radicals generated by
      thermal decomposition of 2,2'-azobis(2,4-dimethylvaleronitrile). Formation of
      these photodecomposition products was inhibited in the presence of sodium azide
      (NaN3), a free radical inhibitor. These results suggest that formation of 5,6
      epoxy-RP, 4-keto-RP, 11-ethoxy-12-hydroxy-RP, and 13-ethoxy-14-hydroxy-RP from
      photoirradiation of RP is mediated by a light-initiated free radical chain
      reaction. AR and the isomeric 11-ethoxy-ARs were not formed from reaction of RP
      with alkylperoxy radicals generated from 2,2'-azobis(2,4-dimethylvaleronitrile),
      and their formation was not inhibited when NaN3 was present during the
      photoirradiation of RP. We propose that these products were formed through an
      ionic photodissociation mechanism, which is similar to the reported formation of
      AR through ionic photodissociation of retinyl acetate. RP and all its identified
      photodecomposition products described above (i) were not mutagenic in Salmonella
      typhimurium tester strains TA98, TA100, TA102, and TA104 in the presence and
      absence of S9 activation enzymes, (ii) were not photomutagenic in Salmonella
      typhimurium TA102 upon UVA irradiation, and (iii) did not bind with calf thymus
      DNA in the presence of microsomal metabolizing enzymes. These results suggest
      that RP and its decomposition products are not genotoxic; however,
      photoirradiation of RP, 5,6-epoxy-RP, and AR with UVA light in the presence of
      methyl linoleate resulted in lipid peroxide (methyl linoleate hydroperoxides)
      formation. The lipid peroxide formation was inhibited by dithiothreitol (DTT)
      (free radical scavenger), NaN3 (singlet oxygen and free radical scavenger), and
      superoxide dismutase (SOD) (superoxide scavenger) but was enhanced by the
      presence of deuterium oxide (D2O) (enhancement of singlet oxygen lifetime). These
      results suggest that photoirradiation of RP, 5,6-epoxy-RP, and AR by UVA light
      generated reactive oxygen species resulting in lipid (methyl linoleate)
      peroxidation.

PMID- 15720117
TI  - Effects of arsenic and UVB on normal human cultured keratinocytes: impact on
      apoptosis and implication on photocarcinogenesis.
AB  - Inorganic arsenic is an environmental toxin and a human carcinogen. Being a co
      mutagen, arsenic enhances carcinogenesis of ultraviolet irradiation on the mouse
      skin. Apoptosis, a well-regulated cell death process, is essential for cell
      development and tissue homeostasis. Dysregulation of apoptosis will lead to
      various kinds of pathological conditions, such as cancers. The purpose of this
      study is to investigate the apoptotic effect induced by the interactions of
      arsenic and UVB on cultured human keratinocytes. Cultured keratinocytes were
      treated with sodium arsenite (1 microM) and/or UVB 50 mJ/cm2 irradiation in
      different combinations, including arsenic alone (As group), UVB alone (UVB
      group), arsenic followed by UVB (As/UVB group), and UVB followed by As (UVB/As
      group) treatments. Our results revealed that a low concentration of sodium
      arsenite did not induce keratinocytes apoptosis. The UVB group showed obvious
      elevation of caspase-8, -9, and -3 activities in addition to strong induction of
      apoptosis as determined by terminal deoxynucleotidyl transferase-mediated
      deoxyuridine nick-end labeling (TUNEL) assay. Similar pro-apoptotic effects were
      observed in the UVB/As group. In contrast, only subtle changes of cell morphology
      and survival rate were noticed in the As/UVB group. In addition, the results of
      Western blot and activity assay of caspase-8, -9, and -3 revealed that neither
      the receptor nor the mitochondrial apoptotic signaling pathway was activated in
      the As/UVB group. Therefore, we conclude that the pretreatment of keratinocytes
      with sodium arsenite decreased the pro-apoptotic effects induced by UVB. This
      finding corroborated with the animal model studying the effects of arsenic and
      UVB on carcinogenesis. The molecular mechanisms by which arsenic decreased UVB
      induced apoptosis remain to be elucidated.

PMID- 15720118
TI  - Mispairing of a site specific major groove (2S,3S)-N6-(2,3,4-trihydroxybutyl)-2'
      deoxyadenosyl DNA Adduct of butadiene diol epoxide with deoxyguanosine: formation
      of a dA(anti).dG(anti) pairing interaction.
AB  - The (2S,3S)-N6-(2,3,4-trihydroxybutyl)-2'-deoxyadenosyl (BDT) adduct arising from
      alkylation of adenine N6 by butadiene diol epoxide (BDE) was placed opposite a
      mismatched deoxyguanosine nucleotide in the complementary strand of the
      oligodeoxynucleotide 5'-d(CGGACXAGAAG)-3'.5'-d(CTTCTGGTCCG)-3'. This
      oligodeoxynucleotide contains codon 61 (underlined) of the human N-ras
      protooncogene. The BDT adduct was at the second position of codon 61, and this
      was named the ras61 S,S-BDT-(61,2) A.G adduct. NMR spectroscopy revealed the
      presence of two conformations of the adducted mismatched duplex. In the major
      conformation, the mismatched base pair X6.G17 was oriented in a "face-to-face"
      orientation, in which both the modified nucleotide X6 and its complement G17 were
      intrahelical and in the anti conformation about the glycosyl bond. Hydrogen
      bonding was suggested between X6 N1 and G17 N1H and between X6 N6H and G17 O6.
      The presence of the BDT moiety allowed formation of a stable A.G mismatch pair.
      The identity of the minor conformation could not be determined. If not repaired,
      the resulting mismatch pair would generate A-->C mutations, which have been
      associated with this adenine N6 BDT adduct [Carmical, J. R., Nechev, L. N.,
      Harris, C. M., Harris, T. M., and Lloyd, R. S. (2000) Env. Mol. Mutagen. 35, 48
      56].

PMID- 15720119
TI  - Dynamic monitoring of cytotoxicity on microelectronic sensors.
AB  - A real-time cell electronic sensing (RT-CES) system was used for label-free,
      dynamic measurement of cell responses to cytotoxicants. Cells were grown onto the
      surfaces of microelectronic sensors, which are comprised of circle-on-line
      electrode arrays and are integrated into the bottom surfaces of the microtiter
      plate. Changes in cell status such as cell number, viability, morphology, and
      adherence were monitored and quantified by detecting sensor electrical impedance.
      For cell quantification and viability measurement, the data generated on the RT
      CES system correlated well with those from the colorimetric (MTT) assay. For
      cytotoxicity assessment, cells growing on microelectronic sensors were treated
      with different cytotoxicants, such as arsenic, mercury, and sodium dichromate.
      The dynamic responses of the cells to the toxicants were continuously monitored
      by the RT-CES system. On the basis of the IC50 values, the RT-CES system displays
      an equal sensitivity to the neutral red uptake assay at specific time points.
      Furthermore, because the RT-CES system provides real-time information regarding
      the state of cell morphology and adhesion in addition to cell number, we were
      able to discern a previously unreported effect of arsenic on NIH 3T3 cells prior
      to cell death. Also, using the RT-CES system, we were able to monitor
      cytotoxicity effects that occur within a minute of compound addition. Taken
      together, the RT-CES system allows for real-time, continuous monitoring and
      quantitative recording of the whole assay process and provides new insight into
      the cell-toxicant interaction.

PMID- 15720120
TI  - Bioactivation of the selective estrogen receptor modulator desmethylated
      arzoxifene to quinoids: 4'-fluoro substitution prevents quinoid formation.
AB  - Although selective estrogen receptor modulators (SERMs) are useful in the
      treatment and prevention of breast cancer, the SERM tamoxifen has been associated
      with an increased risk of endometrial cancer possibly due to metabolism to
      electrophilic quinoids. Another SERM, arzoxifene is currently in clinical trials
      for the treatment of breast cancer, and since it has similar structural
      characteristics to tamoxifen, it also has the potential to form quinoids. In the
      current study, the active form of arzoxifene in vivo, desmethylated arzoxifene
      (DMA), was synthesized and chemically or enzymatically oxidized to DMA diquinone
      methide. The half-life of DMA diquinone methide at physiological pH and
      temperature was approximately 15 s. Reaction of DMA diquinone methide with
      glutathione (GSH) gave four mono-GSH conjugates, two di-GSH conjugates, and one
      tri-GSH conjugate. In incubations of DMA with GSH and either rat or human liver
      microsomes, DMA o-quinone-GSH conjugates were detected in addition to DMA
      diquinone methide-GSH conjugates. A DMA diquinone methide-deoxyguanosine adduct
      was detected following the incubation of DMA diquinone methide with
      deoxynucleosides. In preliminary studies with a human breast cancer cell line,
      DMA induced dose-dependent DNA damage and was more effective at causing DNA
      damage than raloxifene. These results suggest that DMA can be metabolized to
      electrophilic/redox-active quinoids, which have the potential to cause toxicity
      in vivo. A new fluorinated derivative unable to form a diquinone methide, 4'-F
      DMA, was synthesized. 4'-F-DMA showed similar estrogen receptor (ER) binding
      affinity as compared to DMA. The antiestrogenic activity as measured by
      inhibition of estradiol-mediated induction of alkaline phosphatase activity in
      Ishikawa cells showed 10-fold lower activity for 4'-F-DMA compared to DMA;
      however, the antiestrogenic activity was comparable to raloxifene. In microsomal
      incubations of 4'-F-DMA in the presence of GSH, no GSH adducts were detected.
      These data suggest that 4'-F-DMA might be a promising SERM with similar activity
      to DMA and raloxifene and less toxicity.

PMID- 15720121
TI  - Bioactivation of the selective estrogen receptor modulator acolbifene to quinone
      methides.
AB  - Although approved for the treatment of hormone-dependent breast cancer as well as
      for the prevention of breast cancer in high-risk women, the selective estrogen
      receptor modulator (SERM) tamoxifen has been associated with an increased risk of
      endometrial cancer in women. With an understanding of the potential carcinogenic
      mechanisms of these compounds, SERMs could in principle be designed or selected
      for use that avoids these problems. Acolbifene (EM-652) is a fourth-generation
      SERM and the active form of the ester prodrug EM-800. As a pure antagonist of
      breast tumor development and growth, acolbifene does not stimulate endometrial
      tissue. However, acolbifene was found in this investigation to form two kinds of
      quinone methides, either through chemical or through enzymatic oxidation. One was
      a classical acolbifene quinone methide, which was formed by oxidation at the C-17
      methyl group, and the other was a diquinone methide involving the oxidation of
      two phenol groups. The half-life of the classical quinone methide was determined
      to be 32 +/- 0.4 s at physiological pH and temperature. The quinone methides
      reacted with glutathione (GSH) to form five mono-GSH conjugates and five di-GSH
      conjugates. The majority of GSH conjugates resulted from reaction of the
      classical acolbifene quinone methide with GSH. Incubations of acolbifene with GSH
      and either tyrosinase or human and rat liver microsomes also produced acolbifene
      quinone methide-GSH conjugates. In addition to reaction with GSH, the classical
      acolbifene quinone methide was also shown to react with deoxynucleosides. One of
      the major deoxynucleoside adducts was identified as the deoxyadenosine adduct
      resulting from reaction of the classical acolbifene quinone methide with the
      exocyclic amino group of adenine. Acolbifene could also induce DNA damage in the
      S30 breast cancer cell line. These data imply that the classical electrophilic
      acolbifene quinone methide might contribute to the potential toxicity of
      acolbifene.

PMID- 15720122
TI  - Irreversible inactivation of arylamine N-acetyltransferases in the presence of N
      hydroxy-4-acetylaminobiphenyl: a comparison of human and hamster enzymes.
AB  - Arylamine N-acetyltransferases (NATs) catalyze the N-acetylation of arylamines,
      the O-acetylation of N-arylhydroxylamines, and the conversion of N
      (aryl)acetohydroxamic acids to N-acetoxyarylamines. NATs also undergo
      irreversible inactivation in the presence of N-(aryl)acetohydroxamic acids. We
      previously established that inactivation of hamster NAT1 by N-hydroxy-2
      acetylaminofluorene is the result of sulfinamide adduct formation with Cys68. The
      purpose of this research was to determine the kinetics of inactivation of hamster
      NAT1, hamster NAT2, and human NAT1 by N-hydroxy-4-acetylaminobiphenyl (N-OH-4
      AABP), to identify the amino acids that are modified upon NAT-catalyzed
      bioactivation of N-OH-4-AABP, to characterize the adducts and to identify factors
      that influence the propensity of NATs to undergo inactivation by N-arylhydroxamic
      acids. Mass spectrometric analysis of the NATs, after incubation with N-OH-4
      AABP, revealed that the principal adduct of each protein was a (4
      biphenyl)sulfinamide. Proteolysis of the adducted NATs caused hydrolysis of the
      sulfinamides to sulfinic acids. Tandem mass spectrometric analysis of the
      modified peptides revealed that each NAT isozyme contained a sulfinic acid on the
      Cys68 side chain. Minor adducts were identified as 4-aminobiphenyl conjugates of
      tyrosines. Hamster NAT1 was more rapidly inactivated by N-OH-4-AABP than either
      hamster NAT2 or human NAT1, and it was demonstrated that 4-nitrosoobiphenyl,
      which forms the sulfinamide adducts, accumulates during incubation of N-OH-4-AABP
      with hamster NAT2 and human NAT1 but not during incubations with hamster NAT1.
      Steady state kinetic analysis of the hydrolysis of acetylated NATs revealed that
      the half-lives of acetylated hamster NAT2 and human NAT1 are 7-8-fold greater
      than that of acetylated hamster NAT1. These results support the proposal that the
      mechanism of inactivation of NATs by N-OH-4-AABP involves initial deacetylation
      to produce N-OH-4-aminobiphenyl, which after oxidative conversion to 4
      nitrosobiphenyl reacts with Cys68 to form a sulfinamide. The relatively short
      half-life of the acetylated form of hamster NAT1 contributes to its greater
      susceptibility to inactivation by N-OH-4-AABP.

PMID- 15720123
TI  - Classification of the carcinogenicity of N-nitroso compounds based on support
      vector machines and linear discriminant analysis.
AB  - The support vector machine (SVM), as a novel type of learning machine, was used
      to develop a classification model of carcinogenic properties of 148 N-nitroso
      compounds. The seven descriptors calculated solely from the molecular structures
      of compounds selected by forward stepwise linear discriminant analysis (LDA) were
      used as inputs of the SVM model. The obtained results confirmed the
      discriminative capacity of the calculated descriptors. The result of SVM (total
      accuracy of 95.2%) is better than that of LDA (total accuracy of 89.8%).

PMID- 15720124
TI  - Photosensitizing effect of some nonsteroidal antiinflammatory drugs on natural
      and artificial membranes: dependence on phospholipid composition.
AB  - Previous studies have clarified the molecular mechanism of photosensitization on
      red blood cell membranes induced by some drugs belonging to the class of
      nonsteroidal antiinflammatory drugs: ketoprofen, naproxen, and diflunisal. This
      process involves the participation of photodegradation products, free radicals,
      and reactive oxygen species. The aim of the present paper is to investigate the
      photohemolytic process using red blood cells of mammalian species, with different
      membrane phospholipid compositions. Human and bovine red blood cell membranes
      were selectively enriched with phosphatidylcholine and sphingomyelin. For this
      purpose, a new approach for phospholipid investigation was undertaken. Moreover,
      the phototoxic effect was tested with liposomes at different phospholipid
      compositions. A structure-function relationship between the erythrocyte membrane
      phospholipid composition and the photohemolytic process induced by the
      sensitizers can be proposed. Indeed, the different contents of the
      photoperoxidable double bond and the variable architecture of the membrane
      bilayer, due to the different phosphatidylcholine and sphingomyelin contents,
      strongly influence the resistance of the cell to an osmotic shock induced by
      photogenerated transient species or by the lytic activity of drug photoproducts.
      The higher content of sphingomyelin, its asymmetric disposition at the outer
      surface of membrane bilayers, the high level of saturated acyl fatty chains, and
      the presence of photoperoxidable trans double bonds in the hydrophilic region
      greatly decrease the fluidity of bilayers and enhance the resistance of the
      membrane to phototoxic damage. On the other hand, an increase in the content of
      phosphatidylcholine, which is rich in species with unsaturated acyl fatty chains,
      decreases the membrane resistance, because these latter can be easily oxidized by
      drug-photogenerated reactive oxygen species.

PMID- 15720125
TI  - DNA adduct of the mitomycin C metabolite 2,7-diaminomitosene is a nontoxic and
      nonmutagenic DNA lesion in vitro and in vivo.
AB  - Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates and
      cross-links DNA. These effects are dependent on reductive bioactivation of MC.
      2,7-Diaminomitosene (2,7-DAM) is the major metabolite of MC in tumor cells,
      generated by the reduction of MC. 2,7-DAM alkylates DNA in the cell in situ,
      forming an adduct at the N7 position of 2'-deoxyguanosine (2,7-DAM-dG-N7). To
      determine the biological effects of this adduct, we have synthesized an
      oligonucleotide containing a single 2,7-DAM-dG-N7 adduct and inserted it into an
      M13 bacteriophage genome. Replication of this construct in repair-competent
      Escherichia coli showed that the adduct was only weakly toxic and generated
      approximately 50% progeny as compared to control. No mutant was isolated after
      analysis of more than 4000 progeny phages from SOS-induced or uninduced host
      cells; therefore, we estimate that the mutation frequency of 2,7-DAM-dG-N7 was
      less than 2 x 10(-4) in E. coli. Subsequently, to determine if this adduct might
      be mutagenic in mammalian cells, it was incorporated into a single-stranded
      shuttle phagemid vector, pMS2, and replicated in simian kidney (COS-7) cells.
      Analysis of the progeny showed that mutational frequency of a site specific 2,7
      DAM-dG-N7 was not higher than the spontaneous mutation frequency in simian kidney
      cells. In parallel experiments in cell free systems, template oligonucleotides
      containing a single 2,7-DAM-dG-N7 adduct directed selective incorporation of
      cytosine in the 5'-32P-labeled primer strands opposite the adducted guanine,
      catalyzed by Klenow (exo-) DNA polymerase. The adducted templates also supported
      full extension of primer strands by Klenow (exo-) and T7 (exo-) DNA polymerases
      and partial extension by DNA polymerase eta. The innocuous behavior of the 2,7
      DAM-dG-N7 monoadduct in vivo and in vitro is in sharp contrast to that of the
      toxic MC-dG-N2 monoadduct reported earlier.

PMID- 15720126
TI  - Effect of a standardized complex mixture derived from coal tar on the metabolic
      activation of carcinogenic polycyclic aromatic hydrocarbons in human cells in
      culture.
AB  - A complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal
      tar, standard reference material (SRM) 1597, has been shown to initiate tumor
      formation in mouse initiation-promotion assays in our laboratory [(2001)
      Carcinogenesis 22 (7), 1077-1086]. To determine the effects of SRM 1597 on PAH
      activation in human cells, we investigated the PAH-DNA adduct formation in the
      human mammary carcinoma-derived cell line MCF-7. We examined the effects of SRM
      1597 on the metabolic activation to DNA binding derivatives of two carcinogenic
      PAHs, the bay region containing benzo[a]pyrene (B[a]P) and the more carcinogenic
      fjord region containing dibenzo[a,l]pyrene (DB[a,l]P). PAH-DNA adduct analysis by
      33P-postlabeling and reversed phase high-performance liquid chromatography
      revealed a significant decrease in the levels of both B[a]P and DB[a,l]P DNA
      adduct formation on cotreatment with SRM 1597 in comparison to cells exposed to
      B[a]P or DB[a,l]P alone. However, the inhibition of PAH-DNA adduct formation only
      occurred within the first 48 h of exposure in cells cotreated with SRM 1597 and
      B[a]P. In contrast, SRM 1597 significantly inhibited the level of DB[a,l]P DNA
      adducts throughout the 120 h of exposure. Induction of human cytochrome P450
      (P450) enzymes 1A1 and P4501B1 on treatment with SRM 1597 was observed by
      immunoblots. These results suggest that the important factors in determining the
      carcinogenic activity of PAH within a complex mixture would depend on the ability
      of other components of the mixture to promote or inhibit the activation of
      carcinogenic PAH by the induction of P450 enzymes followed by the formation of
      DNA adducts.

PMID- 15720127
TI  - Chlorine substitution pattern, molecular electronic properties, and the nature of
      the ligand-receptor interaction: quantitative property-activity relationships of
      polychlorinated dibenzofurans.
AB  - It was confirmed that both quadrupole moments and polarizabilities of
      polychlorinated dibenzofurans (PCDFs), which were calculated using Hartree-Fock
      theory and/or density functional theory, change systematically with the
      chlorination pattern governing molecular charge distribution. A mathematical
      model based on ligand-receptor binding and solute-solvent interaction is reported
      to explain the difference in toxicity between PCDFs. Multiple regression analysis
      demonstrated that the difference in the potency of aryl hydrocarbon hydroxylase
      (AHH) and 7-ethoxyresorufin O-deethylase (EROD) inductions is mostly determined
      by the polarizabilities of PCDFs. This suggests that the interaction of a PCDF
      with the aryl hydrocarbon receptor (AhR) and its interaction with surrounding
      molecules in the cytosol are dispersion interactions rather than electrostatic
      interactions. Quadrupole moment, electron affinity, and absolute hardness do not
      appear to be significantly correlated with the differences in AHH and EROD
      activities among PCDFs. The entropy change of dissolution is important in
      predicting the AHH and EROD activities with good accuracy. A mathematical model
      is also used to study the differences in AhR binding between PCDFs.

PMID- 15720129
TI  - Detection of DNA damage derived from a direct acting ethylating agent present in
      cigarette smoke by use of liquid chromatography-tandem mass spectrometry.
AB  - Cigarette smoke contains a complex mixture of chemicals, including some that are
      genotoxic. A number of epidemiological and clinical studies have reported the
      association of increased DNA adduct levels with the development of lung cancer in
      smokers. The majority of chemicals present in cigarette smoke require cytochrome
      P450-mediated metabolic activation to form the ultimate reactive species that
      covalently binds with DNA. We have investigated the presence of a direct-acting
      ethylating agent present in cigarette smoke by studying the formation of N-7
      ethylguanine (N-7EtG) following exposure of DNA to cigarette smoke in vitro. A
      sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with
      multiple reaction monitoring (MRM) was developed for the detection of N-7EtG in
      DNA. DNA samples were subjected to thermal hydrolysis to selectively release the
      N-7EtG, which was then quantified by LC-MS/MS MRM using a stable isotope internal
      standard [15N5]N-7EtG. The limit of detection of the method for N-7EtG was 2.0
      fmol injected on column with 100 microg of calf thymus DNA as the matrix (0.6 N
      7EtG adducts per 10(8) nucleotides). A linear dose-response was observed for the
      formation of N-7EtG in calf thymus DNA treated with diethyl sulfate at
      concentrations ranging from 1 to 1000 microM. Calf thymus DNA treated with smoke
      generated from 1, 5, and 10 commercially available cigarettes resulted in the
      formation of 1.3, 3.6, and 8.4 N-7EtG adducts per 10(8) nucleotides,
      respectively. There was a positive correlation between the formation of N-7EtG
      and the number of cigarettes (r = 0.9938). These results confirm the presence of
      an as yet unidentified direct acting ethylating agent in cigarette smoke, which
      is present at levels that can produce DNA damage that could ultimately have
      adverse implications for human health, particularly in the case of the
      development of lung cancer.

PMID- 15720128
TI  - Demonstration by real-time polymerase chain reaction that cellular DNA alkylation
      by novel aminoindoline compounds affects expression of the protooncogene c-myc.
AB  - Aminoindolines, analogues of the potent DNA alkylating agent seco-CBI-TMI, bind
      to and alkylate in the minor groove of AT-rich DNA in vitro. Here we extend the
      in vitro mechanism of action studies by treating cells in culture and examining
      the DNA binding patterns within AT-rich regions of the protooncogene locus c-myc,
      using a real-time polymerase chain reaction (PCR) stop assay. In addition, real
      time reverse transcriptase (RT) PCR is used to examine the immediate effects of
      drug treatment on c-myc expression. These analyses demonstrate a concentration
      and time dependence for DNA alkylation at the chosen sites within the c-myc
      locus, as well as a prompt and significant downregulation of c-myc expression.
      While downregulation of this important growth regulator is likely not the only
      consequence of aminoindoline treatment, these studies begin to address the
      cellular pathways that are involved in the potent cytotoxic effects observed and
      provide insights for the future development of anticancer drugs of this class.

PMID- 15720130
TI  - Induction of cytotoxicity, aldehydic DNA lesions, and poly(ADP-ribose) polymerase
      1 activation by catechol derivatives of pentachlorophenol in calf thymus DNA and
      in human breast cancer cells.
AB  - The purpose of this study was to investigate the degree of chlorination of
      catechol (CAT) derivatives of pentachlorophenol (PCP) on the induction of
      cytotoxicity and DNA damaging effects in calf thymus DNA (ct-DNA) and in two
      human breast carcinoma cell lines. Results indicated that with the addition of
      the transition metal copper(II), increases in the amount of aldehydic DNA lesions
      (ADL) were detected in ct-DNA exposed to PCP-derived CATs over the corresponding
      control. The DNA lesions induced by various degrees of chlorination of PCP
      derived CATs decrease in the rank order CAT congruent with 4-chlorocatechol (4
      ClCAT) > 4,5-dichlorocatechol (4,5-Cl2CAT) > 3,4,5-trichlorocatechol (3,4,5
      Cl3CAT) > tetrachlorocatechol (Cl4CAT). In contrast, Cl4CAT was the only
      congeneric form of PCP-derived catechols that induced a significant increase in
      the number of ADL in human MCF-7 cells, and this only occurred when glutathione
      was depleted. Pretreatment with copper(I) and iron(II) chelators significantly
      reduced the formation of ADL in cells exposed to Cl4CAT. The data also indicated
      that the ADL induced by Cl4CAT in MCF-7 cells contain approximately 70%
      putrescine excisable ADL. This evidence confirmed that the ADL induced by Cl4CAT
      in MCF-7 cells were derived from oxidative events. In addition, we demonstrated
      that the depletion of NAD(P)H in human T47D cells exposed to chlorinated CATs
      decreased in the rank order Cl4CAT >> 4-ClCAT congruent with CAT. The depletion
      of NAD(P)H induced by Cl4CAT in T47D cells was partially blocked by catalase,
      superoxide dismutase, dimethyl sulfoxide, and copper(I) and iron(II) specific
      chelators. Additionally, the depletion of NAD(P)H in T47D cells exposed to Cl4CAT
      (1-10 microM) was completely blocked by three types of poly(ADP-ribose)
      polymerase-1 inhibitors. This evidence suggests that Cl4CAT induces an imbalance
      in DNA repair and the subsequent accumulation of DNA strand breaks in human
      cultured cells. Overall, these findings indicate that dechlorination may decrease
      the potentials of chlorinated catechols to induce oxidative DNA lesions and
      cytotoxic effects in living cells.

PMID- 15720131
TI  - Reactions of benzene oxide with thiols including glutathione.
AB  - S-Phenylmercapturic acid is a minor metabolite of benzene used as a biomarker for
      human benzene exposures. The reaction of intracellular glutathione with benzene
      oxide-oxepin, the initial metabolite of benzene, is presumed to give 1-(S
      glutathionyl)-cyclohexa-3,5-dien-2-ol, which undergoes dehydration to S
      phenylglutathione, the precursor of S-phenylmercapturic acid. To validate the
      proposed route to S-phenylglutathione, reactions of benzene oxide-oxepin with
      glutathione and other sulfur nucleophiles have been studied. The reaction of
      benzene oxide with an excess of aqueous sodium sulfide, followed by acetylation,
      gave bis-(6-trans-5-acetoxycyclohexa-1,3-dienyl)sulfide, the structure of which
      was proved by X-ray crystallography. Reactions of benzene oxide-oxepin in a 95:5
      (v/v) mixture of phosphate buffer in D2O with (CD3)2SO were monitored by 1H NMR
      spectroscopy. In the absence of glutathione, the half-life of benzene oxide
      oxepin was ca. 34 min at 25 degrees C and pD 7.0. The half-life was not affected
      in the range of 2-15 mM glutathione in the presence and absence of a commercial
      sample of human glutathione S-transferase (at pH 7.0, 8.0, 8.5, or 10.0). The
      adduct 1-(S-glutathionyl)-cyclohexa-3,5-diene-2-ol was identified in these
      reaction mixtures, especially at higher pH, by mass spectrometry and by its acid
      catalyzed decomposition to S-phenylglutathione. Incubation of benzene oxide with
      N-acetyl-L-cysteine at 37 degrees C and pH 10.0 and subsequent mass spectrometric
      analysis of the mixture showed formation of pre-S-phenylmercapturic acid and the
      dehydration product, S-phenylmercapturic acid. The data validate the premise that
      benzene oxide-oxepin can be captured by glutathione to give (1R,2R)- and/or
      (1S,2S)-1-(S-glutathionyl)-cyclohexa-3,5-dien-2-ol, which dehydrate to S
      phenylglutathione. The capture is a relatively inefficient process at pH 7 that
      is accelerated at higher pH. These studies account for the observation that the
      metabolism of benzene is dominated by the formation of phenol. The pathway
      leading to S-phenylmercapturic acid is necessarily minor on account of the low
      efficiency of benzene oxide capture by glutathione at pH 7 vs spontaneous
      rearrangement to phenol.

PMID- 15720132
TI  - Metabolic activation of a 1,3-disubstituted piperazine derivative: evidence for a
      novel ring contraction to an imidazoline.
AB  - MB243 (a 1,3-disubstituted piperazine) is a new, potent, and selective
      melanocortin receptor subtype-4 agonist with potential application in the
      treatment of obesity and/or erectile dysfunction. MB243 was observed to
      covalently bind extensively to liver microsomal proteins from rats and humans. In
      the presence of glutathione, two thioether adducts were detected in liver
      microsomal incubations by radiochromatography and LC/MS/MS analysis. These
      adducts were also formed when bile duct-cannulated rats were dosed with MB243.
      The two adducts were isolated, and their structures were determined by accurate
      mass MS/MS and NMR analyses. The proposed structures resulted from a novel
      contraction of the piperazine ring to yield a substituted imidazoline. A
      mechanism is proposed, which involves an initial six electron oxidation of the
      piperazine ring to form a reactive intermediate, which is trapped by glutathione.
      Hydrolysis of the glutamic acid residue followed by internal aminolysis by the
      cysteine amino group resulted in opening of the piperazine ring, which is
      followed by ring closure to an imidazoline. The resulting cysteinyl-glycine
      conjugate underwent subsequent hydrolysis of the glycine residue. Understanding
      of the mechanism of bioactivation led to the design of MB243 analogues that
      exhibited reduced covalent protein binding.

PMID- 15720133
TI  - Monochloroacetic acid inhibits liver gluconeogenesis by inactivating
      glyceraldehyde-3-phosphate dehydrogenase.
AB  - We previously reported that a lethal dose of monochloroacetate (MCA) causes
      severe hypoglycemia and lactic acidosis. MCA has been thought to inhibit
      mitochondrial aconitase; however, the exact effect of MCA on hepatic glucose
      metabolism is not clear. In this study, we investigated the effects of MCA on
      liver gluconeogenesis using an isolated perfused rat liver system.
      Gluconeogenesis from 2.5 mM lactate was inhibited by 1 mM MCA and was completely
      abolished after 2 h of perfusion. Levels of citric acid cycle intermediates such
      as citrate, isocitrate, and 2-oxoglutarate (2-OG) were significantly reduced by
      MCA. The finding that the levels of citrate and 2-OG were similarly reduced (to
      31 and 36% of control, respectively) indicates that aconitase was not inhibited
      by MCA. On the contrary, gluconeogenesis from glycerol, which can be converted to
      glucose without glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was not
      inhibited by MCA. GAPDH was inactivated by MCA in vitro, but enolase,
      phosphoglycerate mutase, and phosphoglycerate kinase were not inactivated at the
      same or higher concentrations of MCA. Furthermore, GAPDH activity in the MCA
      perfused liver decreased to 33-42% of control and that in the liver of rats
      exposed to MCA was reduced to 19% of control. We concluded that MCA inactivates
      GAPDH, and this is the cause of the inhibition of liver gluconeogenesis.

PMID- 15720134
TI  - Detection of a novel mutagen, 3,6-dinitrobenzo[e]pyrene, as a major contaminant
      in surface soil in Osaka and Aichi Prefectures, Japan.
AB  - We previously identified 1,3-, 1,6-, and 1,8-dinitropyrene (DNP) isomers as major
      mutagens in surface soil in three metropolitan areas of Japan. In the present
      study, an organic extract from surface soil collected at a park in Takatsuki in
      Osaka Prefecture, which showed extremely high mutagenicity in Salmonella
      typhimurium TA98 in the absence of mammalian metabolic system (S9 mix), was
      investigated to identify major mutagens. A new powerful bacterial mutagen, as
      well as 1,6- and 1,8-DNP isomers, was isolated from the organic extract (1.8 g)
      of the soil sample (2.2 kg) by column chromatography. On the basis of mass
      spectra, the new mutagen, which accounted for 15% of the total mutagenicity of
      the soil extract, was thought to be a dinitrated polycyclic aromatic hydrocarbon
      with a molecular weight of m/z 342. The mutagen was synthesized from
      benzo[e]pyrene by nitration and was determined to be 3,6-dinitrobenzo[e]pyrene
      (DNBeP) based on its 1H NMR spectrum. The mutagenic potency of 3,6-DNBeP in the
      Ames/Salmonella assay was extremely high, in that it induced 285,000
      revertants/nmol in TA98 and 955,000 revertants/nmol in YG1024 without S9 mix and
      was comparable to those of DNP isomers, which are some the most potent bacterial
      mutagens reported so far. In addition to the soil sample from Takatsuki, 3,6
      DNBeP was also detected in surface soil samples collected at parks in four
      different cities, i.e., Izumiotsu and Takaishi in Osaka Prefecture and Nagoya and
      Hekinan in Aichi Prefecture, and accounted for 22-29% of the total mutagenicity
      of these soil extracts in TA98 without S9 mix. These results suggest that 3,6
      DNBeP is a major mutagen in surface soil and may largely contaminate the surface
      soil in these two regions in Japan.

PMID- 15720135
TI  - Structural characterization of an etheno-2'-deoxyguanosine adduct modified by
      tetrahydrofuran.
AB  - The reaction of 2'-deoxyguanosine with the alpha,beta-unsaturated aldehydes trans
      2-octenal, trans-2-nonenal, trans-2-decenal, trans,trans-2,4-nonadienal, and
      trans,trans-2,4-decadienal in THF gives rise to three novel adducts: 3-(2'-deoxy
      beta-D-erythro-pentafuranosyl)-7-[3-hydroxy-1-(3-(2'-deoxy-beta-D-erythro
      pentafuranosyl)-3,5-dihydro-imidazo[1,2-a]purin-9-one-7-yl)-propyl]-3,5-dihydro
      imidazo[1,2-a]purin-9-one (A7) and 3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7
      (tetrahydrofuran-2-yl)-3,5-dihydro-imidazo[1,2-a]purin-9-one (A8 and A9), which
      are not observed in the absence of THF. These adducts were isolated from in vitro
      reactions by reversed-phase HPLC and fully characterized on the basis of
      spectroscopic measurements. Adduct A7 consists of two 1,N2-etheno-2'
      deoxyguanosine (1,N2-epsilon dGuo) residues linked to a hydroxy-carbon side
      chain; adducts A8 and A9 are interconvertible 1,N2-epsilon dGuo derivatives
      bearing a THF moiety. The proposed reaction mechanism involves the electrophilic
      attack on 1,N2-epsilon dGuo by the carbonyl of 4-hydroxy-butanal, generated via
      ring opening of alpha-hydroxy-THF (THF-OH), yielding adducts A8 and A9. A further
      combination of these adducts with another 1,N2-epsilon dGuo produces the double
      adduct A7. These findings demonstrate that reactions of unsaturated aldehydes in
      the presence of THF produce novel condensation 1,N2-epsilon dGuo-THF adducts.
      Further studies would indicate the relevance of these adducts in THF toxicity.

PMID- 15720136
TI  - Formation of conjugate adducts in the reactions of malonaldehyde-acetaldehyde and
      malonaldehyde-formaldehyde with guanosine.
AB  - The reactions of guanosine with malonaldehyde in buffered aqueous solutions in
      the presence of acetaldehyde or formaldehyde were studied. The reaction mixtures
      were analyzed by RP-HPLC. Two adducts were formed in the reaction of
      malonaldehyde and acetaldehyde and one in the reaction of malonaldehyde and
      formaldehyde. The products were isolated and purified by preparative C-18
      chromatography and structurally characterized by UV absorbance, 1H NMR, and 13C
      NMR spectroscopy and mass spectrometry. The adducts formed in the reaction of
      malonaldehyde and acetaldehyde were identified as 7-(2,2-diformyl-1-methylethyl)
      3-(beta-D-ribofuranosyl)pyrimido[1,2-a]-purin-10(3H)-one (M2AA-Guo I) and 2-(3,5
      diformyl-4-methyl-1,4-dihydro-1-pyridyl)-9-(beta-D-ribofuranosyl)-purin-6(9H)-one
      (M2AA-Guo II). In the reaction of malonaldehyde and formaldehyde, the major
      product was identified as 7-formyl-3-(beta-D-ribofuranosyl)pyrimido[1,2-a]purin
      10(8H)-one (M1FA-Guo). The highest yields of M2AA-Guo I and M2AA-Guo II, 7 and 2
      mol %, respectively, were obtained in the reaction performed at pH 7.4 and 37
      degrees C for 6 days, while M1FA-Guo was produced at a yield of 0.3 mol % after 3
      days of reaction at pH 7.4 and 37 degrees C. The products are formed by reactions
      of malonaldehyde-acetaldehyde and malonaldehyde-formaldehyde condensation
      products with guanosine and are analogous to the previously identified
      condensation products formed with adenosine, cytidine, and proteins.

PMID- 15720137
TI  - A conjugated diene identified as a prohapten: contact allergenic activity and
      chemical reactivity of proposed epoxide metabolites.
AB  - A hapten causing allergic contact dermatitis binds covalently to macromolecules
      via nucleophilic-electrophilic reactions or radical couplings. A prohapten can be
      seen as a chemically inert compound without electrophilic or radical forming
      properties. To exert its activity, the prohapten is activated, for example,
      metabolically, to the hapten. We have investigated the contact allergenic
      properties of a diene, (5R)-5-isopropenyl-2-methyl-1-methylene-2-cyclohexene (1),
      as a potential prohapten, and we found it to be a sensitizer in animal studies.
      The activity is likely to be exerted via epoxide metabolites. Thus, two potential
      metabolites of the investigated diene, (4S)-1,2-epoxy-4-isopropenyl-1-methyl-6
      methylene-cyclohexane (3) and (7R)-7-isopropenyl-4-methyl-1-oxa-spiro[2.5]oct-4
      ene (4), were synthesized and subjected to animal tests. Both epoxides were
      sensitizers. They also elicited significant reactions when tested in animals
      induced with 1, which indicates that they are formed from the diene in the skin.
      Furthermore, incubation of 1 with human liver microsomes produced both epoxides.
      The chemical reactivity of 1, 3, and 4 was investigated in relation to a
      hexapeptide, H-Pro-His-Cys-Lys-Arg-Met-OH. No adducts were obtained from
      reactions between the peptide and 1. However, epoxide 3 bound covalently to the
      cysteine residue and epoxide 4 to both the cysteine and proline residues. Since
      it is possible to relate the sensitizing capacity of a compound to its key
      physicochemical properties, knowledge-based expert systems have been developed to
      predict the toxicity of novel compounds by comparing the structure with activity
      data stored in the computer database. A diene related to 1 found in the knowledge
      based expert system DEREK was considered as a nonsensitizer by this system. Our
      study indicates that conjugated dienes can be metabolized to contact allergens in
      the skin. Thus, when constructing predictive test methods based on SARs, it is
      important to analyze not only the virtual chemical structure of a compound but
      also its ability to act as a prohapten.

PMID- 15720138
TI  - Identification of aldehyde oxidase as the neonicotinoid nitroreductase.
AB  - Imidacloprid (IMI), the prototypical neonicotinoid insecticide, is used worldwide
      for crop protection and flea control on pets. It is both oxidatively metabolized
      by cytochrome P450 enzymes and reduced at the nitroguanidine moiety by a
      previously unidentified cytosolic "neonicotinoid nitroreductase", the subject of
      this investigation. Two major metabolites are detected on incubation of IMI with
      rabbit liver cytosol: the nitrosoguanidine (IMI-NO) and the aminoguanidine (IMI
      NH2). Three lines of evidence identify the molybdo-flavoenzyme aldehyde oxidase
      (AOX, EC 1.2.3.1) as the neonicotinoid nitroreductase. First, classical AOX
      electron donor substrates (benzaldehyde, 2-hydroxypyrimidine, and N
      methylnicotinamide) dramatically increase the rate of formation of IMI
      metabolites. Allopurinol and diquat are also effective electron donors, while
      NADPH and xanthine are not. Second, AOX inhibitors (potassium cyanide, menadione,
      and promethazine) inhibit metabolite formation when N-methylnicotinamide is
      utilized as an electron donor. Without the addition of an electron donor, rabbit
      liver cytosol reduces IMI only to IMI-NO at a slow rate. This reduction is also
      inhibited by potassium cyanide, menadione, and promethazine, as well as by
      additional AOX inhibitors, cimetidine and chlorpromazine. Finally, IMI
      nitroreduction by AOX is sensitive to an aerobic atmosphere, but to a much lesser
      extent than cytochrome P450 2D6. Large species differences are observed in the
      IMI nitroreductive activity of liver cytosol. While rabbit and monkey
      (Cynomolgus) give the highest levels of total metabolite formation, human, mouse,
      cow, and rat also metabolize IMI rapidly. In contrast, dog, cat, and chicken
      liver cytosols do not reduce IMI at appreciable rates. AOX, as a neonicotinoid
      nitroreductase, may limit the persistence of IMI, and possibly other
      neonicotinoids, in mammals.

PMID- 15720139
TI  - From experiment to theory: molecular orbital parameters to interpret the skin
      sensitization potential of 5-chloro-2-methylisothiazol-3-one and 2
      methylisothiazol-3-one.
AB  - 5-Chloro-2-methylisothiazol-3-one (MCI) and 2-methylisothiazol-3-one (MI) are the
      major constituents of the commercial biocide Kathon CG. These two compounds have
      both been shown to exhibit skin sensitization potential: MCI is classified as an
      extreme sensitizer while MI is classified as a moderate sensitizer. The purpose
      of the present investigation was to provide further insights into the chemistry
      underlying their skin sensitizing properties. First, a molecular modeling (in
      silico) study was carried out of the initial reaction pathways of MI and MCI with
      nucleophiles representative of those involved in the skin sensitization process,
      and we compared the findings with the reported chemical and allergenic properties
      of these compounds. These reaction pathways were assessed using molecular orbital
      calculations. A novel parameter, the activation energy (AE) index, is proposed
      and is calculated from a knowledge of the energy changes in the frontier
      molecular orbitals as the electrophile is converted to an anionic intermediate.
      The AE indices correspond to the reactivity of MCI and MI with nucleophiles and
      also their skin sensitization potential. Second, the previously unexplained
      formation of final reaction products from MCI and butylamine is discussed and a
      reaction mechanism is proposed. A key finding of this analysis is that the
      reaction produces "positive chlorine" in the form of N-chloro- and/or N,N
      dichloro-butylamine, which could contribute to the skin sensitizing properties of
      MCI.

PMID- 15720140
TI  - Structure-toxicity relationships for the effects to Tetrahymena pyriformis of
      aliphatic, carbonyl-containing, alpha,beta-unsaturated chemicals.
AB  - Toxicity data for 82 aliphatic chemicals with an alpha,beta-unsaturated
      substructure were compiled. Toxicity was assessed in the 2-day Tetrahymena
      pyriformis population growth impairment assay. Toxic potency [log(IGC50(-1))] for
      most of these chemicals was in excess of baseline narcosis as quantified by the 1
      octanol/water partition coefficient (log K(ow)). The toxicity of the alpha,beta
      unsaturated aldehydes was modeled well by log K(ow) in conjunction with the sum
      of partial charges on the vinylene carbon atoms (Q(C4) + Q(C3)) and the energy of
      the lowest unoccupied molecular orbital (E(lumo)). These electronic descriptors
      were also successful at modeling the toxicity of alpha,beta-unsaturated ketones.
      The toxicity of a range of acrylates was constant within about 0.2 of a log unit.
      Conversely, the toxicity of methacrylates and esters containing the vinylene
      group varied considerably and was explained by their hydrophobicity. The
      comparison of the quantitative structure-activity relationship (QSAR) for the
      methacrylates and esters with that for non-polar narcosis showed little
      significant difference and hence suggested that substitution on the carbon-carbon
      double bond in the methacrylates and vinylene unsaturated esters does not enhance
      toxicity over that of baseline. Substitution on the carbon-carbon double bond in
      the alpha,beta-unsaturated aldehydes resulted in toxicity that was similar to
      that for saturated derivatives. Although an excellent hydrophobicity-dependent
      QSAR was developed for the esters containing ethynylene group, these compounds
      are considered to act as Michael-type acceptors. Attempts to combine different
      groups of Michael-type acceptors into a single QSAR, based on mechanistically
      derived descriptors, were unsuccessful. Thus, the modeling of the toxicity of the
      alpha,beta-unsaturated carbonyl domain is currently limited to models for narrow
      subdomains.

PMID- 15720141
TI  - 2-Alkylpyrrole formation from 4,5-epoxy-2-alkenals.
AB  - N-Substituted 2-pentylpyrrole formation has been related to the etiology or the
      consequences of several diseases in which lipid oxidation is involved. This study
      describes the formation of N-substituted 2-alkylpyrroles in the reaction of 4,5
      epoxy-2-alkenals with amino compounds and suggests an alternative pathway for the
      formation of these compounds that are nowadays commonly accepted to be produced
      by reaction of the lipid oxidation product 4-hydroxy-2-nonenal with primary amino
      compounds. The described reaction constitutes a new route for pyrrole production
      in the lipid peroxidation pathway when it takes place in the presence of amino
      compounds and implies the loss of one carbon in the 4,5-epoxy-2-alkenal during
      the formation of the heterocyclic ring, which is proposed to be released as
      formaldehyde. This reaction also confirms the high reactivity of 4,5-epoxy-2
      alkenals, which are usually found in smaller amounts than other lipid oxidation
      products. Their importance in vivo may be underappreciated in part as a
      consequence of this high reactivity that brings about their rapid disappearance.

PMID- 15720142
TI  - Peroxidation of polyunsaturated fatty acid methyl esters catalyzed by N-methyl
      benzohydroxamic acid: a new and convenient method for selective synthesis of
      hydroperoxides and alcohols.
AB  - A new catalytic system, based on N-methyl benzohydroxamic acid (NMBHA), was
      developed for the selective synthesis of lipid hydroperoxides and alcohols by
      aerobic oxidation of lipid precursors. The reactions were carried out under mild
      conditions with air at atmospheric pressure and 37 degrees C. The products were
      isolated in much better yields (50-60%) as compared to previously reported
      procedures. NMBHA can be recovered at the end of the reaction and recycled. The
      putative reactive intermediate, a nitroxyl radical, readily abstracts a hydrogen
      atom from polyunsaturated lipid precursors such as linoleate esters, and NMBHA
      itself is an excellent hydrogen atom donor, thus conferring high selectivity to
      oxidations catalyzed by this reagent.

PMID- 15720143
TI  - Ternary complexes of gentamicin with iron and lipid catalyze formation of
      reactive oxygen species.
AB  - This study was designed to elucidate the mechanisms underlying the formation of
      reactive oxygen species (ROS) by aminoglycoside antibiotics which may be causally
      related to the toxic side effects of these drugs to the kidney and the inner ear.
      ROS formation by aminoglycosides in vitro requires iron and the presence of
      polyunsaturated lipids as electron donors. Electron spray ionization mass
      spectrometry (ESI-MS) confirmed earlier observations that gentamicin strongly
      binds to L-alpha-phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), a
      membrane lipid rich in arachidonic acid. Studies using lipid-coated membranes
      (PIP strips) further indicated that iron ions and gentamicin can simultaneously
      bind to phosphoinositides with at least one phosphate group on the inositol ring,
      suggesting the existence of ternary complexes among gentamicin, iron, and
      phospholipids. Peroxidation of PtdIns(4,5)P2 by ferrous ions significantly
      increased in the presence of gentamicin, and EI-MS measurements indicated that
      oxidative damage to PtdIns(4,5)P2 was accompanied by the release of arachidonic
      acid. Arachidonic acid also forms a ternary complex with Fe(2+/3+)-gentamicin,
      confirmed by ESI-MS, that reacts with lipid peroxides and molecular oxygen,
      leading to the propagation of arachidonic acid peroxidation.

PMID- 15720144
TI  - Competing roles of cytochrome P450 1A1/1B1 and aldo-keto reductase 1A1 in the
      metabolic activation of (+/-)-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene in human
      bronchoalveolar cell extracts.
AB  - (+/-)-7,8-Dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol), a proximate
      carcinogen derived from benzo[a]pyrene (BP) requires further metabolic activation
      to exert its carcinogenic effects. Two principal pathways have been implicated,
      and these involve either the formation of (+/-)-trans-7,8-dihydroxy
      9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) catalyzed by
      P450 1A1/P450 1B1 (NADPH-dependent monoxygenases) or the formation of
      benzo[a]pyrene-7,8-dione (BP-7,8-dione) catalyzed by human aldo-keto reductases
      AKR1A1 and AKR1C1-AKR1C4 [NAD(P)(H)-dependent oxidoreductases]. The relative
      contributions of the two pathways to PAH activation are unknown. In this study,
      BP-7,8-diol metabolism was studied in human bronchoalveolar H358 cell extracts.
      Parental H358 cells do not constitutively express P450 1A1/P450 1B1 or AKRs but
      were manipulated by induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to
      express P450 1A1/P450 1B1 or by stable transfection to express AKR1A1 (aldehyde
      reductase). TCDD induction of AKR1A1 transfectants provided a cell line that
      expressed both pathways. Extracts derived from parental H358 cells plus TCDD
      (P450 induction) produced electrophilic anti-BPDE, which hydrolyzed to
      benzo[a]pyrene tetrahydrotetrols (BP-tetrols), extracts derived from AKR1A1
      transfected cells (AKR1A1 expression) produced reactive and redox-active BP-7,8
      dione, which was trapped in situ as its mono(thioether) conjugate, and extracts
      derived from AKR1A1 transfectants plus TCDD (coexpression of P450 1A1/P450 1B1
      and AKR1A1) produced both anti-BPDE and BP-7,8-dione. The competing activation of
      BP-7,8-diol by P450 1A1/P450 1B1 and AKR1A1 was studied with varied NADPH:NAD+
      ratios. The system with a relatively higher concentration of NADPH favored
      formation of anti-BPDE via P450 1A1/P450 1B1, while the system with the higher
      concentration of NAD+ favored formation of BP-7,8-dione via AKR1A1. Under
      conditions that mimic the cellular redox state, 10 microM NADPH and 1 mM NAD+,
      equal amounts of BP-tetrols and BP-7,8-dione were formed. This suggests that P450
      1A1/P450 1B1 and AKR1A1 play competing roles in the metabolic activation of BP
      7,8-diol and that the dominant pathway of BP-7,8-diol activation depends on the
      redox state of the cells. These model systems provide a cellular context in which
      the dominant DNA adducts/lesions formed by either pathway may be compared.

PMID- 15720145
TI  - Selective haptenation of cellular or extracellular protein by chemical allergens:
      association with cytokine polarization.
AB  - Sensitizing chemicals can cause different forms of allergy, allergic contact
      dermatitis, or sensitization of the respiratory tract. These discrete types of
      chemicals induce in mice qualitatively divergent immune responses; contact
      allergens provoke preferential type 1 responses, whereas respiratory allergens
      stimulate selective type 2 responses. We have questioned whether the ability of
      chemicals to initiate polarized immune responses is in part a function of the
      nature of their association with protein. Cytokine secretion profiles provoked
      following topical exposure of BALB/c mice to dinitrochlorobenzene (DNCB),
      dinitrofluorobenzene (DNFB), fluorescein isothiocyanate (FITC), trimellitic
      anhydride (TMA), and dinitrobenzenesulfonyl chloride (DNBSCl) were compared with
      the distribution of covalent binding to U937 cells and/or to serum proteins in
      vitro. DNCB and DNFB each provoked a type 1 cytokine secretion profile, with high
      levels of IFN-gamma, but relatively low levels of type 2 cytokines IL-4, -5, and 
      10. The converse selective type 2 phenotype was seen following equivalent
      exposure to TMA, FITC, or DNBSCl. Each chemical bound covalently to U937 cells
      and to serum proteins, when incubated with cells or serum alone. When incubated
      with cells and serum together, DNCB and DNFB bound selectively to cellular
      protein, whereas TMA, FITC, and DNBSCl bound selectively to serum. These
      investigations show that the distribution of antigen formation of chemical
      allergens in an in vitro model system segregates with the type of cytokines
      secreted from activated lymph node cells in an in vivo mouse model. Chemical
      allergens that stimulate type 1 cytokine secretion profiles bind selectively to
      cellular proteins, whereas others that provoke type 2 cytokine profiles bind
      preferentially to serum proteins.

PMID- 15720146
TI  - Quinone methide formations in the Cu(2+)-induced oxidation of a diterpenone
      catechol and concurrent damage on DNA.
AB  - Terpene quinone methides have been isolated from natural resources and exhibit
      broad biological activities against bacteria, fungi, and tumor cells through the
      reactive quinone methide (QM) moiety. The biological potential of the oxidation
      of terpene QM precursors, however, has not been assessed even though Cu(2+)
      induced oxidation of catechol shows detrimental effects on cells. In this study,
      a diterpenone catechol was investigated as a precursor of terpene QM under
      aqueous conditions in the presence of Cu2+. Direct QM formation was implied in
      the Cu(2+)-induced oxidation through the study of thiol addition using HPLC and
      ESI-MS analysis. In addition, oxidation of the initial QM adduct to a second-QM
      intermediate was observed. The direct QM oxidation pathway may be unique for
      diterpenone catechol in the Cu(2+)-induced oxidation and is an addition to the
      reported isomerization pathway of o-quinones to QMs. The DNA damage by the Cu(2+)
      induced oxidation of diterpenone catechol was assessed on a short duplex DNA
      target. Both direct DNA cleavage and nucleobase oxidation were observed
      extensively by in situ-generated hydroxyl radicals.

PMID- 15720147
TI  - Kinetics of nucleotide incorporation opposite polycyclic aromatic hydrocarbon-DNA
      adducts by processive bacteriophage T7 DNA polymerase.
AB  - A series of six oligonucleotides with dihydrodiol epoxide metabolites of the
      polycyclic aromatic hydrocarbons (PAHs) benz[a]anthracene and benzo[a]pyrene
      attached to adenine N6 and guanine N2 atoms were prepared and studied with the
      processive bacteriophage DNA polymerase T7, exonuclease- (T7-). HIV-1 reverse
      transcriptase was much less efficient in polymerization than T7-.
      Benz[a]anthracene and benzo[a]pyrene adducts strongly blocked incorporation of
      dTTP and dCTP opposite the A and G derivatives, respectively. dATP was
      preferentially incorporated in all cases. Steady state kinetic analysis indicated
      that the low catalytic efficiency with adducted DNA was due to both increased
      K(m) and lowered k(cat) values. Some differences due to PAH stereochemistry were
      observed. Fluorescence estimates of K(d) and presteady state kinetic measurements
      of k(off) showed no major decrease in the affinity of T7- with damaged DNA
      substrates or with dNTPs. Presteady state kinetics showed a lack of the normal
      burst kinetics for dNTP incorporation with all PAH-DNA derivatives. These results
      indicate that the rate-limiting step is at or before the step of phosphodiester
      bond formation; release of the oligonucleotide is no longer the slowest step.
      Thio elemental effects (substitution of alpha-oxygen with sulfur) were relatively
      small, in contrast to previous work with T7- and 8-oxo-7,8-dihydroguanine. The
      effect of these bulky PAH adducts is either to attenuate rates of conformational
      changes or to introduce an additional conformation problem but not to alter the
      inherent affinity of the polymerase for DNA or dNTPs.

PMID- 15720150
TI  - Critical appraisal of salting-out and its implications for chemical and
      biological sciences.

PMID- 15720151
TI  - Theoretical exploration of ultrafast dynamics in atomic clusters: analysis and
      control.

PMID- 15720152
TI  - Noncovalent binding between guanidinium and anionic groups: focus on biological-
      and synthetic-based arginine/guanidinium interactions with phosph[on]ate and
      sulf[on]ate residues.

PMID- 15720153
TI  - The structure of active centers and the ethylene polymerization mechanism on the
      Cr/SiO2 catalyst: a frontier for the characterization methods.

PMID- 15720154
TI  - Surface chemistry of transition metal carbides.

PMID- 15720155
TI  - pi-1,1-Dimethyleneallylmetal and homologous complexes: their application in
      organic synthesis.

PMID- 15720156
TI  - Enantioselective enzymatic desymmetrizations in organic synthesis.

PMID- 15720157
TI  - Role of water in electron-initiated processes and radical chemistry: issues and
      scientific advances.

PMID- 15720158
TI  - Photochemical behavior of 6-methylpterin in aqueous solutions: generation of
      reactive oxygen species.
AB  - Pterins are a family of heterocyclic compounds present in a wide range of living
      systems that participate in relevant biological functions and are involved in
      different photobiological processes. 6-Methylpterin (MPT) was investigated for
      its efficiency of singlet-oxygen (1O2) production and quenching in aqueous
      solution. The quantum yields of 1O2 production (phi(delta)) was determined by
      measurements of the 1O2 luminescence in the near-infrared upon continuous
      excitation of the sensitizer. Values of phi(delta) were found to be 0.10 +/- 0.02
      and 0.14 +/- 0.02 in acidic and alkaline media, respectively. Studies of the
      photooxidation of MPT in acidic (pH = 5.0-6.0) and alkaline (pH = 10.2-10.8)
      aqueous solutions at 350 nm and room temperature have been performed. The
      photochemical reactions were followed by UV-visible spectrophotometry, high
      performance liquid chromatography and an enzymatic method for H2O2 determination.
      MPT is not light sensitive in the absence of oxygen, but it undergoes a
      photooxidation reaction in the presence of oxygen, yielding several nonpteridinic
      products. The quantum yields of MPT disappearance were determined and values of
      2.4 (+/-0.5) x 10(-4) and 8.1 (+/-0.8) x 10(-4) were obtained in acidic and
      alkaline media, respectively. H2O2 was detected and quantified in irradiated
      solutions of MPT. The rate constant of the chemical reaction between 1O2 and MPT
      (k(r)) was determined to be 4.9 x 10(6) M(-1) s(-1) in alkaline medium and the
      role of 1O2 in the photooxidation of MPT is discussed.

PMID- 15720159
TI  - Sun exposure and sun protection habits among high-school adolescents in Porto
      Alegre, Brazil.
AB  - Adolescents constitute an important audience for photoprotection programs. Sun
      exposure and sun protection habits acquired during adolescence have a significant
      impact on skin cancer incidence. We administered a questionnaire to 724 students
      about ultraviolet radiation effects, opinions about tanning, total time of sun
      exposure per day, photoprotection and activities in the sun. About 90% were aware
      of the association between sun exposure and skin cancer, and mass media was the
      main source of information. However, the great majority believed that tanning
      improved their appearance, and that it was worth taking the risk. The most
      prevalent outdoor activity among boys was sports; girls preferred walks and
      sunbathing. Sun exposure was significantly longer in summer, when 90% of the
      students went to the beach. About 47% reported sunscreen use in summer and only
      3% reported using sunscreen during winter. These results emphasize the need for
      the promotion of photoprotective habits in our population and the importance of
      engaging physicians and school teachers in developing campaigns directed at this
      issue to achieve effective, long-lasting results. Adolescents are aware of the
      effects of ultraviolet radiation on the skin but campaigns have not successfully
      changed their sun exposure habits.

PMID- 15720160
TI  - Effect of melatonin on brain oxidative damage induced by traumatic brain injury
      in immature rats.
AB  - Progressive compromise of antioxidant defenses and free radical-mediated lipid
      peroxidation, which is one of the major mechanisms of secondary traumatic brain
      injury (TBI), has also been reported in pediatric head trauma. In the present
      study, we aimed to demonstrate the effect of melatonin, which is a potent free
      radical scavenger, on brain oxidative damage in 7-day-old rat pups subjected to
      contusion injury. Whereas TBI significantly increased thiobarbituric acid
      reactive substances (TBARS) levels, there was no compensatory increase in the
      antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) 24 hours after TBI in 7-day-old rats. Melatonin administered as a single
      dose of 5 mg/kg prevented the increase in TBARS levels in both non-traumatized
      and traumatized brain hemispheres. In conclusion, melatonin protects against
      oxidative damage induced by TBI in the immature brain.

PMID- 15720166
TI  - Malaria chemoprophylaxis: in war and peace.

PMID- 15720167
TI  - Screening for venous thrombosis by ultrasonography before hospital discharge
      after major joint surgery.

PMID- 15720168
TI  - Rural health turned upside-down.

PMID- 15720169
TI  - The prevalence of venous thromboembolism after hip and knee replacement surgery.
AB  - OBJECTIVE: To determine the prevalence of venous thromboembolism (VTE) after
      total hip replacement (THR), total knee replacement (TKR) or bilateral TKR in a
      large sample of patients in a major hospital orthopaedic unit. DESIGN, SETTING
      AND PATIENTS: The Mater Misericordiae Hospital, North Sydney, NSW, a 195-bed
      private hospital. All patients who had THR, TKR or bilateral TKR at the hospital
      between 1 April 1995 and 31 December 2001 had physical prophylaxis (graduated
      compression elastic stockings or intermittent pneumatic compression, or both) and
      chemical prophylaxis (anticoagulant) against VTE. All underwent ultrasonography
      of both legs before discharge, with a small, symptomatic group also undergoing a
      ventilation/perfusion lung scan (V/Q scan) and computed tomographic pulmonary
      angiography. MAIN OUTCOME MEASURES: Prevalence of deep-vein thrombosis (DVT) and
      symptomatic pulmonary embolism (PE) before discharge. RESULTS: Among a total of
      5999 patients, the pre-discharge prevalence of DVT after THR, TKR or bilateral
      TKR was 8.9%, 25.6% and 36.9%, respectively. The prevalence of symptomatic non
      fatal in-hospital PE was 1.9%, while the prevalence of fatal in-hospital PE was
      0.05%. CONCLUSIONS: Despite short-term chemical and physical thromboprophylaxis,
      the prevalence of DVT after lower-limb joint replacement, measured by pre
      discharge ultrasonography, was high. The rate of symptomatic non-fatal in
      hospital PE was moderate, but fatal in-hospital PE was rare.

PMID- 15720170
TI  - Quality of stroke care within a hospital: effects of a mobile stroke service.
AB  - OBJECTIVE: An Australian stroke services study (SCOPES) has developed a framework
      to compare different forms of acute stroke services, the gold standard being
      localised stroke units. We aimed to use this framework to assess changes in the
      quality of stroke care over time as a sequential audit process. DESIGN AND
      SETTING: A retrospective medical record audit comparing 100 sequential stroke
      admissions (July 2002 to June 2003) two years after institution of a mobile
      stroke service (MSS) with 100 historical controls (September 1998 to October
      1999) at a 260-bed hospital in Melbourne. The MSS results were also compared with
      stroke units in SCOPES. MAIN OUTCOME MEASURES: Adherence to quality indicators
      and standard measures of outcome (complications, length of stay and discharge
      disability) after implementing the MSS. RESULTS: Significant improvements were
      seen in prophylaxis for deep-vein thrombosis, incontinence management, premorbid
      function documentation, frequent neurological observations and early occupational
      therapy. The MSS demonstrated fewer severe complications (9% versus 24%; P =
      0.004), reduced median length of stay (discharged patients: 12.0 days versus 18.5
      days; P = 0.003) and more patients were independent at discharge (32% versus 9%;
      P < 0.001). Comparison with SCOPES stroke units showed our MSS could improve in
      incontinence management and appropriate use of antiplatelet therapy. CONCLUSION:
      Institution of the MSS was associated with improvements in the quality of stroke
      care. This study demonstrates application of an audit procedure for quality
      improvement in hospital stroke management and the potential to improve stroke
      services in smaller centres.

PMID- 15720171
TI  - Notifications of imported malaria in Western Australia, 1990-2001: incidence,
      associated factors and chemoprophylaxis.
AB  - OBJECTIVE: To assess changes in and factors associated with recent malaria
      notifications in Western Australia (WA). DESIGN: Retrospective analysis of the WA
      Notifiable Infectious Diseases Database and enhanced surveillance questionnaires
      completed by attending medical practitioners. PATIENTS: Cases of malaria notified
      between January 1990 and December 2001. MAIN OUTCOME MEASURES: Annual
      notifications by demographic variables (including age, sex, occupation and place
      of residence), region/country of acquisition, chemoprophylaxis used, Plasmodium
      species and outcome. RESULTS: 482 patients were notified (mean age, 31 years; 80%
      male); 57% lived in Perth, 31% in country areas and 12% in an immigration
      detention centre. Comparison between the 6-year periods 1990-1995 and 1996-2001
      showed that Plasmodium falciparum cases increased from 29 (14%) to 108 (44%; P <
      0.001), while Plasmodium vivax cases decreased from 157 (77%) to 122 (50%; P <
      0.001); immigrants in detention, defence force personnel and cases from Africa
      were increasingly represented (P < 0.05 in each case). Only 31% of patients took
      regular chemoprophylaxis and, among these, the regimen was appropriate in only a
      quarter. There was a median period of 3 days between symptom onset and diagnosis.
      One patient died. CONCLUSIONS: There has been an increase in P. falciparum cases
      in WA since 1990. This reflects the influx of immigrants in detention, deployment
      of military personnel to East Timor and increasing numbers of cases from Africa.
      A significant number of Australian travellers who developed malaria had not taken
      chemoprophylaxis either regularly or at all, and, of those who had, the regimen
      was inadequate in most.

PMID- 15720172
TI  - Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East
      Timor.
AB  - OBJECTIVES: To describe the tolerability of mefloquine in Australian soldiers for
      malaria prophylaxis, including a comparison with doxycycline. DESIGN: Open-label,
      prospective study and cross-sectional questionnaire and interview. SETTING AND
      PARTICIPANTS: Two contingents of Australian soldiers, each deployed to East Timor
      for peacekeeping duties over a 6-month period (April 2001-October 2001 and
      October 2001-May 2002). OUTCOME MEASURES: Withdrawals during the study; adverse
      events relating to mefloquine prophylaxis; willingness to use mefloquine again on
      deployment. RESULTS: Of 1157 soldiers starting on mefloquine, 75 (6.5%) withdrew
      because of adverse responses to the drug. There were three serious adverse events
      of a neuropsychiatric nature, possibly relating to mefloquine. Fifty-seven per
      cent of soldiers using mefloquine prophylaxis reported at least one adverse
      event, compared with 56% using doxycycline. The most commonly reported adverse
      effects of both drugs were sleep disturbance, headache, tiredness and nausea. Of
      the 968 soldiers still taking mefloquine at the end of their deployments, 94%
      indicated they would use mefloquine again. Of 388 soldiers taking doxycycline
      prophylaxis who were deployed with the first mefloquine study contingent, 89%
      indicated they would use doxycycline again. CONCLUSIONS: Mefloquine was generally
      well tolerated by Australian soldiers and should continue to be used for those
      intolerant of doxycycline.

PMID- 15720173
TI  - Clinical experience with the first combined positron emission tomography/computed
      tomography scanner in Australia.
AB  - Metabolic imaging with fluorine-18-fluorodeoxyglucose positron emission
      tomography (FDG-PET) is increasing rapidly worldwide because of superior accuracy
      compared with conventional non-invasive techniques used for evaluating cancer.
      Limited anatomical information from FDG-PET images alone dictates that
      complementary use with structural imaging is required to optimise benefit.
      Recently, combined positron emission tomography/computed tomography (PET/CT)
      scanners have overtaken standalone PET scanners as the most commonly purchased
      PET devices. We describe our experience of over 5500 scans performed since the
      first PET/CT scanner in Australia was commissioned at the Peter MacCallum Cancer
      Centre (PMCC), Melbourne, in January 2002. Clinical indications for PET/CT scans
      performed at PMCC largely reflect current Medicare reimbursement policy.
      Advantages of PET/CT include greater patient comfort and higher throughput,
      greater diagnostic certainty and accuracy, improved biopsy methods, and better
      treatment planning. We believe PET/CT will underpin more effective and efficient
      imaging paradigms for many common tumours, and lead to a decrease in imaging
      costs.

PMID- 15720174
TI  - Postgraduate medical education: rethinking and integrating a complex landscape.
AB  - A key responsibility of the healthcare system is to develop a sustainable
      workforce through education and training. The complexity of postgraduate medical
      education and training in Australia requires: recognition that there are many
      stakeholders (junior medical officers, registrars, teaching clinicians, health
      departments, governments, colleges and society) with overlapping but competing
      interests and responsibilities; a national dialogue to clarify the necessary
      resource investments and to assign explicit accountabilities; and improved
      coordination and governance, while maintaining appropriate flexibility. In other
      countries, stronger mechanisms of governance for oversight of postgraduate
      medical education have emerged, and Australia can learn from these.

PMID- 15720175
TI  - Artemisinin-based combination therapies for uncomplicated malaria.
AB  - There has been a relentless increase in resistance of malaria parasites to
      conventional antimalarial drugs, including chloroquine, sulfadoxine-pyrimethamine
      and mefloquine. In response to this situation, short-course artemisinin-based
      combination therapies (ACTs) have been developed. The World Health Organization
      has endorsed ACT as first-line treatment where the potentially life-threatening
      parasite Plasmodium falciparum is the predominant infecting species. ACTs combine
      the rapid schizontocidal activity of an artemisinin derivative (artesunate,
      artemether or dihydroartemisinin) with a longer-half-life partner drug. Although
      the use of chloroquine and sulfadoxine-pyrimethamine as partners in ACT improves
      their efficacy, this may only have value as a short-term measure in patients with
      a degree of immunity to malaria. Alternative currently available partner drugs
      include mefloquine, lumefantrine and piperaquine. Artesunate-mefloquine is highly
      effective but is expensive and side effects (mainly neurotoxicity) can be
      problematic. Artemether-lumefantrine, the only ACT available in Australia,
      appears less effective than artesunate-mefloquine and needs to be administered
      with food to ensure adequate bioavailability. Dihydroartemisinin-piperaquine is
      highly effective, well tolerated and relatively inexpensive. The goal of potent,
      safe, easy-to-administer and inexpensive ACTs may see trioxolanes in place of
      artemisinin derivatives, as well as novel partner drugs such as pyronaridine or
      naphthoquine, in the future.

PMID- 15720176
TI  - Chronic falciparum malaria causing massive splenomegaly 9 years after leaving an
      endemic area.
AB  - A 28-year-old woman from Sudan who had lived for 9 years in Victoria, Australia,
      was diagnosed with falciparum malaria 2 months after splenectomy for massive
      splenomegaly of unknown cause. Chronic falciparum malaria can occasionally
      present years after leaving endemic areas in partially immune patients. It should
      be considered in such patients with presentations possibly related to malaria,
      including splenomegaly, anaemia, or a long history of intermittent fevers and
      chills.

PMID- 15720178
TI  - COX-2 selectivity varies across class.

PMID- 15720177
TI  - 4. Bedwetting and toileting problems in children.
AB  - Bedwetting (nocturnal enuresis) is common. It occurs in up to 20% of 5 year olds
      and 10% of 10 year olds, with a spontaneous remission rate of 14% per year.
      Weekly daytime wetting occurs in 5% of children, most of whom (80%) also wet the
      bed. Bedwetting can have a considerable impact on children and families,
      affecting a child's self-esteem and interpersonal relationships, and his or her
      performance at school. Primary nocturnal enuresis (never consistently dry at
      night) should be distinguished from secondary nocturnal enuresis (previously dry
      for at least 6 months). Important risk factors for primary nocturnal enuresis
      include family history, nocturnal polyuria, impaired sleep arousal and bladder
      dysfunction. Secondary nocturnal enuresis is more likely to be caused by factors
      such as urinary tract infections, diabetes mellitus and emotional stress. The
      treatment for monosymptomatic nocturnal enuresis (bedwetting with no daytime
      symptoms) is an alarm device, with desmopressin as second-line therapy. Treatment
      for non-monosymptomatic nocturnal enuresis (bedwetting with daytime symptoms-
      urgency and frequency, with or without incontinence) should initially focus on
      the daytime symptoms.Bedwetting without daytime symptoms, the most common
      toileting problem, can be effectively treated with an alarm device.

PMID- 15720179
TI  - Withdraw all COX-2-selective drugs.

PMID- 15720180
TI  - Possible genetic predisposition to cardiac effects.

PMID- 15720182
TI  - Acute presentation of childhood hypothyroidism.

PMID- 15720184
TI  - MDM2 is a central node in the p53 pathway: 12 years and counting.
AB  - Twelve years ago, the Mdm2 oncogene was shown to bind to and inhibit the tumor
      suppressor protein, p53. During the past 12 years, both genetic and biochemical
      studies have demonstrated that Mdm2 is a key negative regulator of the tumor
      suppressor p53. Mdm2 and p53 form an oscillating auto-regulatory feedback loop,
      which is tightly controlled to allow the appropriate response to environmental
      stresses in order to suppress tumor formation. When Mdm2 activity is
      inappropriately heightened, as it is in many human tumors, p53 activity is
      attenuated and tumor susceptibility arises. The p53 gene is mutated in 50% of all
      human tumors, but in those tumors that retain wild type p53, inhibiting Mdm2
      activity could activate p53 tumor suppression and therefore provide a therapeutic
      strategy for the treatment of cancer.

PMID- 15720185
TI  - p53-independent activities of MDM2 and their relevance to cancer therapy.
AB  - The feed-back auto-regulatory loop between p53 and MDM2 has been extensively
      investigated. MDM2 is under the transcriptional control of p53, and MDM2 acts as
      a negative regulator of p53. There is increasing evidence, however, supporting
      the notion that MDM2 has activities independent of p53. In the absence of p53,
      MDM2 may retain its role in cell cycle control, differentiation, cell fate
      determination, DNA repair, transcription regulation, signal transduction of
      steroid receptors, cellular response to hypoxia, internalization of surface
      receptors, and other processes. MDM2 also has oncogenic transformational
      activities independent of p53. Moreover, anti-MDM2 antisense oligonucleotides
      have in vitro and in vivo antitumor activity and chemosensitizing and
      radiosensitizing effects in several human cancer models, regardless of their p53
      status. In this article, the p53 independent activities of MDM2 and its
      interactions with various cellular proteins are considered. The studies reviewed
      provide a basis for developing novel MDM2 inhibitors as a therapy against human
      malignancies.

PMID- 15720186
TI  - MDM2 splice variants and their therapeutic implications.
AB  - MDM2 splice variants have now been identified in many different tumor types, and
      their expression has been associated with advanced disease. However, published
      data concerning their function is contradictory, and therefore their role in
      tumorigenesis and their potential as a therapeutic target are unclear. Expression
      of a specific splice variant, MDM2-B, in a transgenic mouse model results in
      tumor development; and expression of several splice variants has been shown to
      enhance tumor formation in Emu-myc transgenic mice. However, expression of
      similar variants in vitro results in growth inhibition, an observation
      inconsistent with a transformed phenotype. The observed growth inhibition is p53
      dependent, resulting from the binding of splice variants with an intact C
      terminal RING finger domain to full-length MDM2 protein. In doing so, p53 can no
      longer bind MDM2, and p53 activity is elevated. Subsequent inactivation of p53 or
      p53-mediated apoptosis could contribute to the MDM2 splice variant-mediated
      tumorigenesis observed in vivo. However, MDM2 splice variants, like full-length
      MDM2, probably display p53-independent activities. Therefore, the potential for
      MDM2 splice variants as therapeutic targets will be dependent upon their
      phenotype within specific tumor types.

PMID- 15720187
TI  - MDM2 and human malignancies: expression, clinical pathology, prognostic markers,
      and implications for chemotherapy.
AB  - The human homologue of the mouse double minute 2 (MDM2) oncogene is overexpressed
      in more than forty different types of malignancies, including solid tumors,
      sarcomas and leukemias. Because of its prevalent expression and its interactions
      with p53 and other signaling molecules, MDM2 plays a central role in cancer
      development and progression. The expression of this oncoprotein is being studied
      by researchers world-wide, and the amount of data published about it is
      increasing exponentially. Although there are some conflicting data about the
      effects of MDM2 expression in individual cancers, the overall evidence is
      convincing, indicating that increased MDM2 expression is related to a worse
      clinical prognosis. There is an increased likelihood of distant metastases, as
      well as a decreased response to therapeutic intervention in MDM2-positive
      cancers. MDM2 may also serve as a diagnostic marker, not only for cancer stage,
      but to differentiate between similar cancers. MDM2 may also be associated with
      drug resistance in cancer chemotherapy. These findings make studying the
      oncoprotein necessary to aid in our understanding of cancer development, to
      identify novel cancer drug targets, and to increase the efficacy of cancer
      therapy.

PMID- 15720188
TI  - Novel antisense anti-MDM2 mixed-backbone oligonucleotides: proof of principle, in
      vitro and in vivo activities, and mechanisms.
AB  - The MDM2 oncogene has been suggested as a novel target for cancer therapy, based
      on the following observations: 1) MDM2 is overexpressed in many human cancers,
      including breast, colon, and prostate cancer; 2) high MDM2 levels are associated
      with poor prognosis in patients with cancer; 3) MDM2 overexpression is associated
      with advanced cancer phenotypes such as metastatic tumors and hormone-independent
      tumors; 4) MDM2 overexpression is associated with tumor resistance to
      chemotherapy and radiation therapy; and 5) inhibiting MDM2 expression or function
      results in tumor growth inhibition and regression. There are many options for
      inhibiting MDM2 function, including the use of gene silencing technologies,
      antibodies, peptides and small molecules. Considering the complexity of MDM2
      functions, we have chosen to use gene silencing technologies including antisense
      oligonucleotides and RNA interference. In this article, we summarize the
      investigation of the antisense technology for inhibiting MDM2 expression.
      Antisense mixed-backbone oligonucleotides (MBO) specifically inhibit MDM2
      expression in a dose- and time-dependent manner, resulting in significant anti
      tumor activity in vitro and in vivo. The MBO also potentiates the therapeutic
      effects of chemotherapeutic agents and radiation therapy in various tumors,
      through both p53-dependent and p53-independent mechanisms, indicating that MDM2
      inhibitors have a broad spectrum of anti-tumor activity in human cancers,
      regardless of p53 status. These results provide a basis for clinical evaluation
      of antisense anti-MDM2 oligonucleotides as chemosensitizers and radiosensitizers.
      In addition, the MBO has been successfully used to identify novel functions of
      MDM2.

PMID- 15720189
TI  - Chemosensitization by antisense oligonucleotides targeting MDM2.
AB  - The MDM2 oncogene is overexpressed in many human cancers, including sarcomas,
      certain hematologic malignancies, and breast, colon and prostate cancers. The p53
      MDM2 interaction pathway has been suggested as a novel target for cancer therapy.
      To that end, several strategies have been explored, including the use of small
      polypeptides targeted to the MDM2-p53 binding domain, anti-MDM2 antisense
      oligonucleotides, and natural agents. Different generations of anti-human-MDM2
      oligonucleotides have been tested in in vitro and in vivo human cancer models,
      revealing specific inhibition of MDM2 expression and significant antitumor
      activity. Use of antisense oligos potentiated the effects of growth inhibition,
      p53 activation and p21 induction by several chemotherapeutic agents. Increased
      therapeutic effectiveness of chemotherapeutic drugs in human cancer cell lines
      carrying p53 mutations or deletions have shown the ability of MDM2 inhibitors to
      act as chemosensitizers in various types of tumors through both p53-dependent and
      p53-independent mechanisms. Inhibiting MDM2 appears to also have a role in
      radiation therapy for human cancer, regardless of p53 status, providing a
      rationale for the development of a new class of radiosensitizers. Moreover, MDM2
      antisense oligonucleotides potentiate the effect of epidermal growth factor
      receptor (EGFR) inhibitors by affecting in vitro and in vivo proliferation,
      apoptosis and protein expression in hormone-refractory and hormone-dependent
      human prostate cancer cells. These data support the development, among other MDM2
      inhibitors, of anti-MDM2 antisense oligonucleotides as a novel class of
      anticancer agents, and suggest a potentially relevant role for the
      oligonucleotides when integrated with conventional treatments and/or other
      signaling inhibitors in novel therapeutic strategies.

PMID- 15720193
TI  - Structure-based drug discovery for Plasmodium falciparum.
AB  - X-ray crystallography is a technique which is finding increasing utility in the
      effort to find new antimalarial drugs. This is in spite of the serious
      difficulties often encountered in obtaining sufficient quantities of protein to
      crystallize. This review provides an overview of the Plasmodium falciparum
      proteins which have been crystallized with bound inhibitors and the methodology
      employed in the heterologous expression of these proteins. Lactate dehydrogenase,
      plasmepsin II, and triosphosphate isomerase are the most advanced targets of
      structure-based drug design, but nine other P. falciparum proteins have been
      crystallized with inhibitors as well, and this is clearly an area which is moving
      very quickly. Some consideration will also be given to the limitations of
      structure-based drug discovery with respect to known antimalarial drugs.

PMID- 15720190
TI  - Small molecule antagonists of the MDM2 oncoprotein as anticancer agents.
AB  - In this early phase of the new era of molecularly targeted patient friendly
      cancer chemotherapy, there is a need for novel viable anticancer molecular
      targets. The MDM2 oncoprotein has been validated as a potential target for cancer
      drug development. MDM2 amplification and/or overexpression occur in a wide
      variety of human cancers, several of which can be treated experimentally with
      MDM2 antagonists. MDM2 interacts primarily with the p53 tumor suppressor protein
      in an autoregulatory negative feedback loop to attenuate p53's cell cycle arrest
      and apoptosis functions. Inhibition of the p53-MDM2 interaction has been shown to
      cause selective cancer cell death, as well as sensitize cancer cells to
      chemotherapy or radiation effects. Consequently, this interaction has been the
      main focus of anticancer drug discovery targeted to MDM2. The promotion of the
      proteasomal degradation of the p53 protein by MDM2 is central to its repression
      of the tumor suppressor functions of p53, and many proteins impinge upon this
      activity, either enhancing or inhibiting it. MDM2 also has oncogenic activity
      independent of its interaction with p53, but this has so far not been explored
      for drug discovery. Among the approaches for targeting MDM2 for cancer therapy,
      small molecule antagonists have recently featured as effective anticancer agents
      in experimental models, although the repertoire is currently limited and none has
      yet entered human clinical trials. Small molecules that have been reported to
      disrupt the p53-MDM2 binding, thereby enhancing p53 activity to elicit anticancer
      effects include the following: synthetic chalcones, norbornane derivatives, cis
      imidazoline derivatives (Nutlins), a pyrazolidinedione sulfonamide and 1,4
      benzodiazepine-2,5-diones, as well as tryptophan derivatives. In addition to
      compounds disrupting p53pMDM2 binding, three compounds have been discovered that
      are effective in inhibiting the E3 ligase activity of MDM2 towards p53, and
      should serve as leads for drug discovery targeting this aspect of the p53-MDM2
      interaction as well. These compounds were discovered from library screening
      and/or structure-based rational drug design strategies.

PMID- 15720194
TI  - Fatty Acid synthesis as a target for antimalarial drug discovery.
AB  - In biological systems, fatty acids can be synthesized by two related, but
      distinct de novo fatty acid synthase (FAS) pathways. Human cells rely on a type I
      FAS whereas plants, bacteria and other microorganisms contain type II FAS
      pathways. This difference exposes the type II FAS enzymes as potential targets
      for anti-microbial drugs that have little to no side effects in the human host. A
      number of inhibitors of type II FAS enzymes have been discovered - many of which
      have anti-bacterial activity. Extensive biochemical and structural studies have
      shed light on how these compounds inhibit their target enzymes, laying the
      foundation for the design of inhibitors with increased potency. Recent work has
      shown that malaria parasites do not contain a type I FAS and rely solely on a
      type II FAS for the de novo biosynthesis of fatty acids. The malaria FAS enzymes
      are therefore an exciting source of new drug targets, and are being actively
      exploited by several drug discovery efforts. Rapid progress has been made,
      largely due to the vast body of mechanistic and structural information about type
      II FAS enzymes from bacteria and the availability of inhibitors. Ongoing
      antimalarial drug discovery projects will be described in this review as well as
      background information about the well-studied bacterial type II FAS enzymes.

PMID- 15720195
TI  - Rational inhibitor design and iterative screening in the identification of
      selective plasmodial cyclin dependent kinase inhibitors.
AB  - New chemical classes of compounds must be introduced into the malaria drug
      development pipeline in an effort to develop new chemotherapy options for the
      fight against malaria. In this review we describe an iterative approach designed
      to identify potent inhibitors of a kinase family that collectively functions as
      key regulators of the cell cycle. Cyclin-dependent protein kinases (CDKs) are
      attractive drug targets in numerous diseases and, most recently, they have become
      the focus of rational drug design programs for the development of new
      antimalarial agents. Our approach uses experimental and virtual screening
      methodologies to identify and refine chemical inhibitors and increase the success
      rate of discovering potent and selective inhibitors. The active pockets of the
      plasmodial CDKs are unique in terms of size, shape and amino acid composition
      compared with those of the mammalian orthologues. These differences exemplified
      through the use of screening assays, molecular modeling, and crystallography can
      be exploited for inhibitor design. To date, several classes of compounds
      including quinolines and oxindoles have been identified as selective inhibitors
      of the plasmodial CDK7 homologue, Pfmrk. From these initial studies and through
      the iterative rational drug design process, more potent, selective, and most
      importantly, chemically unique compound classes have been identified as effective
      inhibitors of the plasmodial CDKs and the malarial parasite.

PMID- 15720196
TI  - 1,4-bis(3-aminopropyl)piperazine libraries: from the discovery of classical
      chloroquine-like antimalarials to the identification of new targets.
AB  - The purpose of this review is to provide an update on our work based on the 1,4
      bis(3-aminopropyl)piperazine skeleton and how it allowed our group to validate a
      new target. After a brief introduction where we will relate the way this
      substructure was introduced in our 4-aminoquinolinyl derivatives, we will present
      first the different libraries synthesized around this moiety: (1) libraries of
      sulfonamides, amides and amines derived from 4-aminoquinolines and, (2) libraries
      where the 4-aminoquinoline nucleus is replaced. High throughput evaluation of
      biological activity and physicochemical parameters will be presented. The
      evaluation of the anti-malarial activity of the compounds will be discussed in
      the light of a chloroquine-like mechanism (accumulation in the acidic food
      vacuole and inhibition of beta-hematin formation). In a second part we will
      present active 1,4-bis(3-aminopropyl)piperazine as tools for identification
      and/or validation of new antimalarial targets. Fluorescence assays on some
      derivatives show that they are surprisingly localized outside the food vacuole,
      suggesting the existence of other target(s). Secondly, we will present a library
      of 1,4-bis(3-aminopropyl)piperazine as inhibitors of the cytosolic aminopeptidase
      Pfa-M1, a new potential target for antimalarials.

PMID- 15720197
TI  - Dual molecules as new antimalarials.
AB  - A new antimalarial pharmacological approach based on inhibition of the plasmodial
      phospholipid metabolism has been developed. The drugs mimic choline structure and
      inhibit de novo phosphatidylcholine biosynthesis. Three generations of compounds
      were rationally designed. Bisquaternary ammonium salts showed powerful
      antimalarial activity, with IC(50) in the nanomolar range. To remedy their low
      per os absorption, bioisosteric analogues (bis-amidines) were designed and
      exhibited similar powerful activities. Finally, the third generation compounds
      are bis-thiazolium salts and their non-ionic precursors: prodrugs, which in vivo
      can lead to thiazolium drugs after enzymatic transformation. The compounds are
      equally effective against multiresistant Plasmodium falciparum malaria. These
      molecules exert a very rapid cytotoxic effect against malarial parasites in the
      very low nanomolar range and are active in vivo against P. vinckei-infected mice,
      with ED(50) lower than 0.2 mg/kg. They are able to cure highly infected mice and,
      retain full activity after a single injection. They also retain full activity
      against P. falciparum and P. cynomolgi in primate models with no recrudescence
      and at lower doses. Compounds are accumulated in P.falciparum-infected
      erythrocyte, which ensures their potency and specificity. Recently, we discovered
      that compounds also interact with malarial pigment enhancing the antimalarial
      effect. It is quite likely that they are dual molecules, exerting their
      antimalarial activity via two simultaneous toxic effects on the intracellular
      intraerythrocytic parasites. The current leader compounds are accessible in few
      steps from commercial products. These crystalline molecules present a remarkable
      biological activity and low toxicity which is promising for the development of a
      new antimalarial drug.

PMID- 15720198
TI  - Targeting the hemozoin synthesis pathway for new antimalarial drug discovery:
      technologies for in vitro beta-hematin formation assay.
AB  - Clinical manifestations of malaria primarily result from proliferation of the
      parasite within the hosts' erythrocytes. During this process, hemoglobin is
      utilized as the predominant source of nutrition. The malaria parasite digests
      hemoglobin within the digestive vacuole through a sequential metabolic process
      involving multiple proteases. Massive degradation of hemoglobin generates large
      amount of toxic heme. Malaria parasite, however, has evolved a distinct mechanism
      for detoxification of heme through its conversion into an insoluble crystalline
      pigment, known as hemozoin. Hemozoin is identical to beta-hematin, which is
      constituted of cyclic heme dimers arranged in an ordered crystalline structure
      through intermolecular hydrogen bonding. The exact mechanism of biogenesis of
      hemozoin in malaria is still obscure and is the subject of intense debate.
      Hemozoin synthesis is an indispensable process for the parasite and is the target
      for action of several known antimalarials. The pathway has therefore attracted
      significant interest for new antimalarial drug discovery research. Formation of
      beta-hematin may be achieved in vitro under specific chemical and physiochemical
      conditions through a biocrystallization process. Based on these methods several
      experimental approaches have been described for the assay of formation of beta
      hematin in vitro and screening of compounds as inhibitors of hemozoin synthesis.
      These assays are primarily based on differential solubility and spectral
      characteristics of monomeric heme and beta-hematin. Different factors viz., the
      malaria parasite lysate, lipids extracts, preformed beta-hematin, malarial
      histidine rich protein II and some unsaturated lipids have been employed for
      promoting beta-hematin formation in these assays. The assays based on
      spectrophotometric quantification of beta-hematin or incorporation of (14)C-heme
      yield reproducible results and have been applied to high throughput screening.
      Several novel antimalarial pharmacophores have been discovered through these
      assays.

PMID- 15720199
TI  - The new permeability pathways: targets and selective routes for the development
      of new antimalarial agents.
AB  - The malaria parasite, Plasmodium falciparum, spends part of its complex life
      cycle within the red blood cells of a human host. During this time, the parasite
      alters the permeability of the red blood cell's plasma membrane to allow the
      uptake of nutrients, the removal of "waste" and volume and ion regulation of the
      infected cell. The increased permeability is due to the induction of new
      permeability pathways (NPP), which are obvious chemotherapeutic antimalarial
      targets and/or selective routes for drugs, which target the internal parasite.
      This review covers our present understanding of the NPP, the methods used to
      screen for putative inhibitors of the NPP, the current repertoire of NPP
      inhibitors and the problems that need to be addressed to realise the potential of
      the NPP as antimalarial targets. In addition, the review will cover the use of
      the NPP as specific drug delivery routes.

PMID- 15720200
TI  - The role of in vitro ADME assays in antimalarial drug discovery and development.
AB  - The high level of attrition of drugs in clinical development has led
      pharmaceutical companies to increase the efficiency of their lead identification
      and development through techniques such as combinatorial chemistry and high
      throughput (HTP) screening. Since the major reasons for clinical drug candidate
      failure other than efficacy are pharmacokinetics and toxicity, attention has been
      focused on assessing properties such as metabolic stability, drug-drug
      interactions (DDI), and absorption earlier in the drug discovery process. Animal
      studies are simply too labor-intensive and expensive to use for evaluating every
      hit, so it has been necessary to develop and implement higher throughput in vitro
      ADME screens to manage the large number of compounds of interest. The
      antimalarial drug development program at the Walter Reed Army Institute of
      Research, Division of Experimental Therapeutics (WRAIR/ET) has adopted this
      paradigm in its search for a long-term prophylactic for the prevention of
      malaria. The overarching goal of this program is to develop new, long half-life,
      orally bioavailable compounds with potent intrinsic activity against liver- and
      blood-stage parasites. From the WRAIR HTP antimalarial screen, numerous compounds
      are regularly identified with potent activity. These hits are now immediately
      evaluated using a panel of in vitro ADME screens to identify and predict
      compounds that will meet our specific treatment criteria. In this review, the
      WRAIR ADME screening program for antimalarial drugs is described as well as how
      we have implemented it to predict the ADME properties of small molecule for the
      identification of promising drug candidates.

PMID- 15720202
TI  - Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and
      endothelial dysfunction.
AB  - Hyperhomocyst(e)inemia is associated with an increased risk for atherosclerotic
      disease and venous thromboembolism. The impact of elevated plasma homocysteine
      levels seems to be clinically relevant, since the total cardiovascular risk of
      hyperhomocyst(e)inemia is comparable to the risk associated with hyperlipidemia
      or smoking. There is substantial evidence for impairment of endothelial function
      in human and animal models of atherosclerosis, occurring even before development
      of overt plaques. Interestingly endothelial dysfunction appears to be a sensitive
      indicator of the process of atherosclerotic lesion development and predicts
      future vascular events. NO is the most potent endogenous vasodilator known. It is
      released by the endothelium, and reduced NO bioavailability is responsible for
      impaired endothelium-dependent vasorelaxation in hyperhomocyst(e)inemia and other
      metabolic disorders associated with vascular disease. Substances leading to
      impaired endothelial function as a consequence of reduced NO generation are
      endogenous NO synthase inhibitors such as ADMA. Indeed there is accumulating
      evidence from animal and human studies that ADMA, endothelial function and
      homocyst(e)ine might be closely interrelated. Specifically elevations of ADMA
      associated with impaired endothelium-dependent relaxation were found in chronic
      hyperhomocyst(e)inemia, as well as after acute elevation of plasma homocyst(e)ine
      following oral methionine intake. The postulated mechanisms for ADMA accumulation
      are increased methylation of arginine residues within proteins, as well as
      reduced metabolism of ADMA by the enzyme DDAH, but they still need to be
      confirmed to be operative in vivo. Hyperhomocyst(e)inemia, as well as subsequent
      endothelial dysfunction can be successfully treated by application of folate and
      B vitamins. Since ADMA seems to play a central role in homocyst(e)ine-induced
      endothelial dysfunction, another way of preventing vascular disease in patients
      with elevated homocyst(e)ine concentrations could be supplementation with L
      arginine to reverse the detrimental effects of ADMA.

PMID- 15720203
TI  - Effects of betaine intake on plasma homocysteine concentrations and consequences
      for health.
AB  - High plasma concentrations of homocysteine may increase risk of cardiovascular
      disease. Folic acid lowers plasma homocysteine by 25% maximally, because 5
      methyltetrahydrofolate is a methyl donor in the remethylation of homocysteine to
      methionine. Betaine (trimethylglycine) is also a methyl donor in homocysteine
      remethylation, but effects on homocysteine have been less thoroughly
      investigated. Betaine in high doses (6 g/d and higher) is used as homocysteine
      lowering therapy for people with hyperhomocysteinemia due to inborn errors in the
      homocysteine metabolism. Betaine intake from foods is estimated at 0.5-2 g/d.
      Betaine can also be synthesized endogenously from its precursor choline. Studies
      in healthy volunteers with plasma homocysteine concentrations in the normal range
      show that betaine supplementation lowers plasma fasting homocysteine dose
      dependently to up to 20% for a dose of 6 g/d of betaine. Moreover, betaine
      acutely reduces the increase in homocysteine after methionine loading by up to
      50%, whereas folic acid has no effect. Betaine doses in the range of dietary
      intake also lower homocysteine. This implies that betaine can be an important
      food component that attenuates homocysteine rises after meals. If homocysteine
      plays a causal role in the development of cardiovascular disease, a diet rich in
      betaine or choline might benefit cardiovascular health through its homocysteine
      lowering effects. However betaine and choline may adversely affect serum lipid
      concentrations, which can of course increase risk of cardiovascular disease.
      However, whether the potential beneficial health effects of betaine and choline
      outweigh the possible adverse effects on serum lipids is as yet unclear.

PMID- 15720204
TI  - Homocysteine and the kidney.
AB  - Plasma homocysteine concentration exhibits a strong relationship with (indices
      of) renal function. Hyperhomocysteinemia has been implicated in the high vascular
      event rate in patients with chronic renal failure. The precise pathophysiological
      explanation for the occurrence of hyperhomocysteinemia in renal failure is not
      yet elucidated. A defective intrinsic renal metabolism of homocysteine seems
      unlikely. There are several indications that whole body homocysteine metabolism
      is altered in renal insufficiency. Stable isotope studies in dialysis patients
      have shown a decreased homocysteine clearance by transsulfuration and decreased
      homocysteine remethylation and methionine transmethylation. Several, but not all,
      prospective studies have linked hyperhomocysteinemia to adverse cardiovascular
      outcomes in renal failure patients. Treatment of hyperhomocysteinemia in renal
      insufficiency is based on folic acid-containing regimens, but so far, none of the
      regimens has been shown to successfully normalize plasma homocysteine
      concentration. Intervention studies have not yet demonstrated beneficial vascular
      effects of homocysteine-lowering treatment in dialysis patients.

PMID- 15720205
TI  - Mechanisms of increased vascular oxidant stress in hyperhomocys-teinemia and its
      impact on endothelial function.
AB  - Elevated plasma levels of homocysteine are associated with an increased
      generation of reactive oxygen species in aortas of hyperhomocysteinemic animals
      and in endothelial cells. This may contribute to endothelial dysfunction observed
      in hyperhomocysteinemia, and promote atherosclerotic vascular disease.
      Homocysteine seems to promote the formation of reactive oxygen species primarily
      by a biochemical mechanism involving endothelial nitric oxide synthase, as
      increased endothelial lipid peroxidation and oxidation of the redox-sensitve dye
      2',7'-dichlorofluoresceine could only be observed after incubation of endothelial
      cells with L-, but not with D-homocysteine, and could be prevented by inhibition
      of endothelial nitric oxide synthase. An increased oxidation rate of aminothiols
      in plasma, as observed in patients with hyperhomocysteinemia, further contributes
      to increased generation of reactive oxygen species. These effects are amplified
      by a homocysteine-specific inhibition of cellular antioxidant enzymes, like
      superoxide dismutase and the cellular isoform of gluthatione peroxidase. All
      mechanisms together result in increased levels of superoxide anion and peroxyl
      radicals in the vasculature that react with nitric oxide to form peroxnitrites.
      This abolishes nitric oxide's bioactivity and contributes to endothelial
      dysfunction. In addition, increased vascular oxidant stress in
      hyperhomocysteinemia has been shown to activate proinflammatory signaling
      pathways in endothelial cells, like the transcription factor NF-kappaB. This
      leads to increased endothelial expression of chemokines and adhesion molecules
      that promote the recruitment, adhesion and transmigration of circulating
      leukocytes to the vessel wall. All these mechamisms may contribute to the
      increased risk for cardiovascular diseases associated with hyperhomocysteinemia.

PMID- 15720206
TI  - Gene-nutrient interactions in one-carbon metabolism.
AB  - Advances in molecular biology greatly contributed, in the past decades, to a
      deeper understanding of the role of gene function in disease development.
      Environmental as well as nutritional factors are now well acknowledged to
      interact with the individual genetic background for the development of several
      diseases, including cancer, cardiovascular disease, and neurodegenerative
      diseases. The precise mechanisms of such gene-nutrient interactions, however, are
      not fully elucidated yet. Many micronutrients and vitamins are crucial in
      regulating mechanisms of DNA metabolism. Indeed, folate has been most extensively
      investigated for its unique function as mediator for the transfer of one-carbon
      moieties for nucleotide synthesis/repair and biological methylation. Cell
      culture, animal, and human studies, clearly demonstrated that folate deficiency
      induces disruption of DNA synthesis/repair pathways as well as DNA methylation
      anomalies. Remarkably, a gene-nutrient interaction between folate status and a
      polymorphism in methylenetetrahydrofolate reductase gene has been reported to
      modulate genomic DNA methylation. This observation suggests that the interaction
      between a nutritional status and a mutant genotype may modulate gene expression
      through DNA methylation, especially when such polymorphism affects a key enzyme
      in one-carbon metabolism and limits the methyl supply. DNA methylation, both
      genome-wide and gene-specific, is of particular interest for the study of aging,
      cancer, and other pathologic conditions, because it affects gene expression
      without permanent alterations in the DNA sequence such as mutations or allele
      deletions. Understanding the patterns of DNA methylation through the interaction
      with nutrients is a critical issue, not only to provide pathophysiological
      explanations of a disease state, but also to identify individuals at-risk to
      conduct targeted diet-based interventions.

PMID- 15720207
TI  - The usefulness of holotranscobalamin in predicting vitamin B12 status in
      different clinical settings.
AB  - Serum concentrations of homocysteine (Hcy) and methylmalonic acid (MMA) become
      increased in B12-deficient subjects and are therefore, considered specific
      markers of B12 deficiency. Serum level of holotranscobalamin (holoTC) becomes
      decreased before the development of the metabolic dysfunction. We investigated
      the usefulness of holoTC in diagnosing B12 deficiency in some clinical settings.
      We measured serum concentrations of holoTC, MMA, Hcy and total B12 in omnivores,
      vegetarians, elderly people and haemodialysis patients. Our results indicated
      that the incidence of holoTC <35 pmol/L was highest in the vegans (76%). Low
      holoTC and elevated MMA were detected in 64% of the vegans and 43% of the lacto-
      and lacto-ovovegetarians. An elevated MMA and a low holoTC were found in subjects
      with total serum B12 as high as 300 pmol/L. The distribution of holoTC in elderly
      people was similar to that in younger adults (median holoTC 55 pmol/L in both
      groups). A low holoTC and an elevated MMA were found in 16% of the elderly group.
      An elevated MMA and a normal holoTC were found in 20% of the elderly group who
      had a relatively high median serum concentration of creatinine (106.1
      micromol/L). Serum concentrations of holoTC in dialysis patients were
      considerably higher than all other groups (median 100 pmol/L). This was also
      associated with severely increased serum levels of MMA (median 987 nmol/L). From
      these results it can be concluded that serum concentration of holoTC is a much
      better predictor of B12 status than total B12. This was particularly evident in
      case of dietary B12 deficiency. Serum concentrations of holoTC as well as MMA can
      be affected by renal dysfunction. Elevated MMA and normal holoTC in patients with
      renal insufficiency may not exclude vitamin B12 deficiency. HoloTC seems not to
      be a promising marker in predicting B12 status in renal patients.

PMID- 15720209
TI  - Stem cell therapy for myelin diseases.
AB  - Advances in cell biology have encouraged the hope that stem cell-based therapy
      can be used to heal central nervous system (CNS) diseases. Here, we will review
      the potential application of neural cell transplantation for the treatment of
      multiple sclerosis (MS) and other demyelinating disorders, mention some
      problematic issues that still face this therapeutic approach, and describe novel
      noninvasive methods for in vivo tracking of transplanted cells.

PMID- 15720210
TI  - Small interfering RNAs and antisense oligonucleotides for treatment of
      neurological diseases.
AB  - The complexity of the central nervous system (CNS) exposes it to a number of
      different diseases, often caused by only small variations in gene sequence or
      expression level. Antisense oligonucleotides and RNA interference-mediated
      therapies hold great promise for the treatment of CNS diseases in which
      neurodegeneration is linked to overproduction of endogenous protein or to
      synthesis of aberrant proteins coded by dominant mutant alleles. Nevertheless,
      difficulties related to the crossing of the blood-brain barrier, expression
      vectors, molecule design and to the choosing of the correct target, should be
      effectively solved. This review summarizes some of the most recent findings
      concerning the administration of potential nucleic acid-based therapeutic drugs,
      as well as the most promising studies performed both in vitro and in animal
      models of disease. Finally, some current clinical trials involving antisense
      oligonucleotides or silencing RNA for therapy of neurological disorders are
      illustrated. Results of current studies and clinical trials are exciting, and
      further results will be certainly reached with increasing knowledge of blood
      brain barrier transporters, of genes involved in neurological disease and in new
      vectors for efficient delivery to brain.

PMID- 15720211
TI  - Integral therapeutic potential of bone marrow mesenchymal stem cells.
AB  - Bone marrow derived mesenchymal stem cells (MSC) are adult stem cells that reside
      within the bone marrow compartment. In the traditional developmental model, adult
      stem cells are able to differentiate only to the tissue in which they reside.
      Recent data have challenged the committed fate of the adult stem cells,
      presenting evidence for their multi-lineage differentiation potential. In
      addition, potential therapeutic benefits of MSC administration have been the main
      concern of much research, including clinical trials. These studies promote adult
      stem cell therapy by shedding some light on the therapeutic potential of MSC and
      their mechanism of action. Many doubts have found their way into MSC research.
      They question MSC potency and beneficial contribution. However, these obstacles
      should not arrest but set a challenge to MSC researchers to examine their
      achievements under a magnifying glass. Therapeutic benefits of MSC exogenous
      delivery do not run counter to its possible participation in endogenous repair.
      Several reports imply MSC involvement in physiological repair but no explicit
      data support this hypothesis. This review tries to put MSC research into
      perspective. Possible therapeutic applications of MSC therapy for damaged tissue
      replacement, tissue engineering and the underlying repair mechanisms will be
      discussed. In addition, reported data about MSC possible involvement in
      physiological multiple tissue repair, their homing to injury and site-specific
      differentiation will be presented.

PMID- 15720212
TI  - Huntington's disease: new frontiers for molecular and cell therapy.
AB  - Huntington's disease (HD) is an incurable, adult-onset, dominantly inherited
      neurodegenerative disease, caused by a CAG expansion in the 5' coding region of
      the gene HD [encoding huntingtin (htt), which is ubiquitously expressed in all
      tissues]. The disease progresses inexorably with devastating clinical effects on
      motor, cognitive and psychological functions; death occurring approximately 18
      years from the time of onset. These clinical symptoms primarily relate to the
      progressive death of medium-spiny GABA-ergic neurons of the striatum and in the
      deep layers of the cortex; during the later stages of the disease, the
      degeneration extends to a variety of brain regions, including the hypothalamus
      and hippocampus. The mechanism by which mutant htt leads to neuronal cell death
      and the question of why striatal neurons are targeted both remain to be further
      investigated. Certainly htt is required for cell survival and impairment of wild
      type htt function can be involved in neurodegeneration, but considerable evidence
      also shows that trinucleotide repeat expansion into glutamine (polyQ domain)
      endows the protein with a newly acquired toxic activity. The increasing
      availability of HD animal models have allowed not only to investigate the
      function of htt, but also to screen and test potential therapeutic drugs in the
      promising area of neurotherapeutics. So, thorough analysis of these molecular and
      biochemical events, assessing the validity of candidate mechanisms, provides a
      means to identify effective therapeutic strategies for cellular repair. Here, the
      rationale and efficacy of different therapies are compared and alternative
      therapies are reviewed including intrastriatal transplantation of human fetal
      striatal tissue to support the cell replacement strategy in HD. Since functional
      restoration through neuronal replacement probably could be combined with
      neuroprotective strategies for optimum clinical benefit, in vivo and ex vivo gene
      therapy for delivery of neuroprotective growth factor molecules are also
      considered.

PMID- 15720213
TI  - Stem cell therapy for neurologic disorders: therapeutic potential of adipose
      derived stem cells.
AB  - There is growing evidence to suggest that reservoirs of stem cells may reside in
      several types of adult tissue. These cells may retain the potential to
      transdifferentiate from one phenotype to another, presenting exciting
      possibilities for cellular therapies. Recent discoveries in the area of neural
      differentiation are particularly exciting given the limited capacity of neural
      tissue for intrinsic repair and regeneration. Adult adipose tissue is a rich
      source of mesenchymal stem cells, providing an abundant and accessible source of
      adult stem cells. These cells have been termed adipose derived stem cells (ASC).
      The characterization of these ASCs has defined a population similar to marrow
      derived and skeletal muscle-derived stem cells. The success seen in
      differentiating ASC into various mesenchymal lineages has generated interest in
      using ASC for neuronal differentiation. Initial in vitro studies characterized
      the morphology and protein expression of ASC after exposure to neural induction
      agents. Additional in vitro data suggests the possibility that ASCs are capable
      of neuronal activity. Progress in the in vitro characterization of ASCs has led
      to in vivo modeling to determine the survival, migration, and engraftment of
      transplanted ASCs. While work to define the mechanisms behind the
      transdifferentiation of ASCs continues, their application to neurological
      diseases and injuries should also progress. The subject of this review is the
      capacity of adipose derived stem cells (ASC) for neural transdifferentiation and
      their application to the treatment of various neurologic disorders.

PMID- 15720214
TI  - Adult stem cell application in spinal cord injury.
AB  - The mechanical force incurred by spinal cord injury results in degenerative
      neural tissue damage beyond the site of initial injury. By nature, the central
      nervous system (CNS) does not regenerate itself. Cell therapy, in particular,
      stem cell implantation has become a possible solution for spinal cord injury.
      Embryonic stem cells and fetal stem cells are the forefathers of the field of
      stem cell therapy. Isolation and preparation of specific populations of adult
      stem cells have evolved to the point of stable, long-term culturing with the
      capability to differentiate into neural phenotypes from all three of the neural
      lineages: neurons, astrocytes, and oligodendrocytes. Thus, adult stem cells will
      transcend ethical concerns, technical difficulties, and probably immunorejection.
      A variety of adult stem cells have been implanted in a rat model of spinal cord
      injury, ranging from olfactory ensheathing cells, cultured spinal cord stem
      cells, bone marrow derived stem cells, dermis derived stem cells, and a few
      others. Although no definite decisions on which adult stem cells are most
      effective for this CNS injury, their ability to incorporate into the spinal cord,
      differentiate, and to improve locomotor recovery hold promise for a cure.

PMID- 15720215
TI  - Neuropathic pain: is the end of suffering starting in the gene therapy?
AB  - Neuropathic pain is defined as pain initiated or caused by a primary lesion or
      dysfunction in the nervous system. It is a devastating and difficult to manage
      consequence of peripheral nerve injury and has a variety of clinical symptoms.
      Neuropathic pain is a major health problem. It has been estimated that 70% of
      patients with advanced cancer and inflammatory pathologies are afflicted by
      chronic pain. About 95% of patients with spinal cord injuries have neuropathic
      pain problems. Chronic pain is debilitating and cause of depression and
      decreasing quality of life. Pharmacological treatment for the symptoms of painful
      neuropathy is difficult, because there has been limited understanding of the
      underlying causes and systemic levels that an effective dose can have on multiple
      side effects. The use of molecular methods, such as gene therapy, stem cell
      therapy and viral vector for delivery of biologic antinociceptive molecules, has
      led to a better understanding of the underlying mechanisms of the induction of
      intractable neuropathic pain.

PMID- 15720216
TI  - Combining polymeric devices and stem cells for the treatment of neurological
      disorders: a promising therapeutic approach.
AB  - Cell therapy will probably become a major therapeutic strategy for neuronal
      disorders in the coming years. Nevertheless, due to poor survival of grafted
      cells and limited differentiation and integration in the host tissue, certain
      ameliorations must be envisaged. To address these difficulties, several
      strategies have been developed and among them, two methods seem particularly
      promising : in situ controlled drug delivery and implantation of cells adhered on
      biomaterial-based scaffolds. Indeed, the ability of drugs, such as growth
      factors, to regulate neuronal survival and/or plasticity infers the use of these
      molecules to treat neurodegeneration associated with human diseases. Moreover,
      the synthesis of cell scaffolds which mimic the extra-cellular matrix can help
      guide morphogenesis and tissue repair. Furthermore, cells can be cultivated on
      these matrices that may eventually make graft therapy a more practical approach
      for the treatment of neurological diseases. Nevertheless, for those two
      encouraging approaches multiple parameters have to be considered, such as the
      drug targeting strategy, but also the physical and morphological characteristics
      of the scaffold and the type of cells to be conveyed. This review thus focuses on
      those two promising strategies and also on their possible association to improve
      stem cell therapy of neurodegenerative disorders. Indeed, tissue replacement by
      grafting cells within or adhered onto drug delivering biomaterial-based devices,
      has recently been reported and seems to be very promising.

PMID- 15720217
TI  - Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical
      transplantation.
AB  - Neural stem cells (NSCs) are present not only in the developing nervous systems,
      but also in the adult human central nervous system (CNS). It is long thought that
      the subventricular zone of the lateral ventricles and the dentate gyrus of the
      hippocampus are the main sources of human adult NSCs, which are considered to be
      a reservoir of new neural cells. Recently adult NSCs with potential neural
      capacity have been isolated from white matter and inferior prefrontal subcortex
      in the human brain. Rapid advances in the stem cell biology have raised appealing
      possibilities of replacing damaged or lost neural cells by transplantation of in
      vitro-expanded stem cells and/or their neuronal progeny. However, sources of stem
      cells, large scale expansion, control of the differentiations, and tracking in
      vivo represent formidable challenges. In this paper we review the characteristics
      of the adult human NSCs, their potentiality in terms of proliferation and
      differentiation capabilities, as well as their large scale expansion for clinical
      needs. This review focuses on the major advances in brain stem cell-based therapy
      from the clinical perspective, and summarizes our work in clinical phase I-II
      trials with autologuous transplantation of adult NSCs for patients with open
      brain trauma. It also describes multiple approaches to monitor adult human NSCs
      labeled superparamagnetic nanoparticles after transplantation and explores the
      intriguing possibility of stem cell transplantation.

PMID- 15720218
TI  - Endogenous and exogenous CNS derived stem/progenitor cell approaches for
      neurotrauma.
AB  - Neural stem/progenitor cells capable of generating new neurons and glia, reside
      in specific areas of the adult mammalian central nervous system (CNS), including
      the ependymal region of the spinal cord and the subventricular zone (SVZ),
      hippocampus, and dentate gyrus of the brain. Much is known about the neurogenic
      regions in the CNS, and their response to various stimuli including injury,
      neurotrophins (NFs), morphogens, and environmental factors like learning, stress,
      and aging. This work has shaped our current views about the CNS's potential to
      recover lost tissue and function post-traumatically and the therapies to support
      the intrinsic regenerative capacity of the brain or spinal cord. Recently,
      intensive research has explored the potential of harvesting, culturing, and
      transplanting neural stem/progenitors as a therapeutic intervention for spinal
      cord injury (SCI) and traumatic brain injury (TBI). Another strategy has focused
      on maximizing the potential of this endogenous population of cells by stimulating
      their recruitment, proliferation, migration, and differentiation in vivo
      following traumatic lesions to the CNS. The promise of such experimental
      treatments has prompted tissue and biomaterial engineers to implant synthetic
      three-dimensional biodegradable scaffolds seeded with neural stem/progenitors
      into CNS lesions. Although there is no definitive answer about the ideal cell
      type for transplantation, strong evidence supports the use of region specific
      neural stem/progenitors. The technical and logistic considerations for
      transplanting neural stem/progenitors are extensive and crucial to optimizing and
      maintaining cell survival both before and after transplantation, as well as for
      tracking the fate of transplanted cells. These issues have been systematically
      addressed in many animal models, that has improved our understanding and approach
      to clinical therapeutic paradigms.

PMID- 15720220
TI  - Hyaluronan and hyaluronan synthases: potential therapeutic targets in cancer.
AB  - Current models of oncogenesis describe cancer as a progression of genetic
      mutations in a tumor cell mass. However, tumors are more than a clonal expansion
      of malignant cells. Tumors are heterogeneous, with a complex 3D structure,
      analogous to organs comprised of different tissues. In a tumor mass, the
      component cell types interact with each other and with their microenvironment by
      exchanging information through cell-cell interactions and/or through interactions
      with the extracellular matrix (ECM). These synergetic interactions facilitate
      tumor progression. Furthermore, tumor invasion and metastatic development are
      accomplished through the breakdown of ECM. Disruption of ECM promotes abnormal
      inter- and/or intra- cellular signaling, leading to dysregulation of cell
      proliferation, growth and cytoskeleton reorganization. The disruption of the ECM
      in turn promotes the overproduction of growth factors, which induce elevated
      epithelial cell proliferation and other abnormalities including carcinogenesis.
      In this review we will demonstrate that hyaluronan (HA), a core component of ECM,
      contributes to certain types of cancer development. Additional to extracellular
      HA, intracellular and nuclear forms of HA have been detected. Intracellular HA is
      involved in cell signaling, whereas nuclear HA could promote chromatin
      condensation and thus facilitate mitosis. HA molecules are synthesized by
      hyaluronan synthases (HASs)-HAS1, HAS2 and HAS3 enzymes. Dysregulation of HAS
      genes results in abnormal production of HA and promotion of abnormal biological
      processes such as transformation and metastasis. The function of HASs appears to
      be cell and tissue specific. HAS1 maintains a low, basal level of HA. HAS2 is
      involved in embryonic and cardiac cushion morphogenesis and subsequent
      development through cell migration and invasion. HAS2 stimulates cell
      proliferation and angiogenesis. HAS3 appears to favor the malignant phenotype in
      many types of malignancies. However, the exact function of HAS isoenzymes and
      their role in cell signaling remains to be elucidated. A better understanding of
      HA and HASs may facilitate the design of novel therapeutic strategies to counter
      presumptive cancer-promoting effects of microenvironmental components.

PMID- 15720222
TI  - ABC transporters and sterol absorption.
AB  - Recent molecular studies, in particular investigations of subjects with monogenic
      disorders of lipoprotein metabolism and studies of induced-mutant mice, have
      increased the understanding of intestinal sterol absorption. Some of these genes
      encode adenosine triphosphate [ATP] binding cassette (ABC) transporters that
      transport dietary cholesterol from enterocytes back out to the intestinal lumen,
      thereby limiting the amount of cholesterol absorbed. ABC transporters also
      provide an effective barrier against the absorption of plant sterols, which are
      normally not absorbed in significant quantities by humans. This mechanism was
      clarified by the discovery that defects in two adjacent genes encoding ABC
      transporters are the molecular basis of sitosterolemia, a rare autosomal
      recessive disease in which plant sterols are absorbed due to failure of
      intestinal barrier to their absorption. Furthermore, recent experiments performed
      in induced-mutant mice have solidified the importance of these transporters in
      intestinal sterol absorption. Together with new developments in the biology of
      bile acids, sterol absorption is providing interesting directions for metabolism
      research. In addition to elucidating some of the molecular mechanisms of sterol
      absorption, these recent findings may lead to new therapeutic options to treat
      hypercholesterolemia and to help patients at risk of vascular disease reach ever
      more stringent target levels.

PMID- 15720221
TI  - The future of angiotensin II inhibition in cardiovascular medicine.
AB  - Drugs, which interfere with the renin-angiotensin-aldosterone cascade such as
      angiotensin converting enzyme (ACE) inhibitors, have been available to clinicians
      for more than 20 years. They are now recognized as a very effective approach to
      treat patients with hypertension, heart failure, diabetic and non-diabetic
      chronic renal failure or patients with a high cardiovascular risk. The recent
      development of angiotensin II (Ang II) receptor antagonist has enabled to improve
      significantly the tolerability profile of this group of drugs while maintaining a
      high clinical efficacy. Yet, with the availability of Ang II receptor
      antagonists, new questions have arisen. Is it still possible to gain in efficacy
      with newer agents? What is the future of drugs such as neutral endopeptidase
      (NEP)/ACE inhibitors or renin inhibitors? The first objective of this review is
      to discuss the clinical implications of several large clinical trials that have
      been published recently with ACE inhibitors and Ang II receptor antagonists such
      as ALLHAT, LIFE, OPTIMAAL, Val-Heft, SCOPE, and more recently, CHARM, VALIANT and
      VALUE. With these trials, we can now define more precisely the role of these
      blockers of the renin-angiotensin system in the management of patients with
      cardiovascular complications. The second part of this review is devoted to new
      drugs interfering with the renin-angiotensin system. We discuss the recent
      results obtained with NEP/ACE inhibitors also named vasopeptidase inhibitors.
      Several compounds were or are in development but the experience with omapatrilat
      has blunted the enthusiasms for these compounds. Yet, vasopeptidase inhibitors
      remain very effective antihypertensive drugs and there is a great therapeutic
      potential for these agents provided one can define more accurately the
      risk/benefit ratio and the clinical indications. Finally, we present the recent
      data obtained with SPP 100, a new renin inhibitor that is actually under clinical
      development. SPP 100 has a sufficient bioavailability to induce a sustained
      blockade of the renin-angiotensin system when given orally to normal subjects.
      Recent studies have shown that SPP 100 lowers blood pressure in hypertensive
      patients as effectively as an Ang II receptor antagonist.

PMID- 15720223
TI  - Cancer metastasis: characterization and identification of the behavior of
      metastatic tumor cells and the cell adhesion molecules, including carbohydrates.
AB  - This review focuses on the behavior of metastatic tumor cells and their specific
      adhesion molecules. Much of this review is based on the results from our
      researches over many years. Electron microscopic investigations of metastatic
      processes have demonstrated that desmosomes, tight junctions, or cell fusion-like
      structures are formed between tumor cells and other cells such as endothelial,
      mesothelial, hepatic, and nerve cells. These findings suggest that metastatic
      tumor cells acquire specific cell adhesion or recognition systems. To investigate
      these adhesion mechanisms, we established floating sublines from rat ascites
      hepatoma AH7974 in vitro and compared their adhesion molecules with those of
      their adherent counterparts. The anchorage independence of these tumor cells can
      be explained by reduced production of extracellular matrix proteins, decreased
      expression of cell surface integrin(s), or lack of heparan sulfate proteoglycans
      on the cell surfaces. Although the metastatic potential of these sublines for
      lung could not be explained by these properties, it may be explained by
      expression of 56 and 62 kDa laminin-like substances containing Griffonia
      Bandeirea simplicifolia isolectin B4-binding carbohydrate(s). We examined the
      relationship between carbohydrate expression and metastasis of human breast,
      pulmonary, colorectal, gastric, and other cancers by using a panel of lectins and
      monoclonal antibodies (MAbs). These studies revealed that several lectins and
      MAbs such as Vicia villosa agglutinin (VVA), Helix pomatia agglutinin, anti
      sialyl Lewis(x-i) MAb, and others were useful not only for predicting metastasis
      and the prognosis of patients but also for understanding the routes of metastatic
      spread. VVA-binding carbohydrates, i.e. N-acetyl-D-galactosamine residues,
      especially those carried by atypical MUC1 protein, in aggressive cancer cells may
      serve as an important drug target.

PMID- 15720224
TI  - Nitric oxide and its antithrombotic action in the cardiovascular system.
AB  - Nitric oxide (NO) is a small gaseous molecule with an odd number of electrons and
      is rather soluble in hydrophobic phases. It was once known for its toxicity in
      the environment and for its applications in meat curing. After 1980 its
      importance was discovered in many physiological fields such as vascular
      regulation, neuronal communication, cytotoxic action by macrophages in bacterial
      infections etc. On the other side NO is involved in toxic shock, DNA damage and
      many pathological conditions. In 1992 the journal Science designated it as
      "molecule of the year" and in the last years there has been an explosion of
      publications on the subject. The publications are concerned with the
      spectroscopic characterisation of NO derivatives, with the reactivity of NO with
      Myoglobin, Cytochrome and Hemoglobin and in particular with the chemical
      activities and biological applications of nitric oxide donors and nitric oxide
      scavengers. All such researches have produced until now many patents. The most
      famous products are Viagra and nitroglycerine (Trinitrin). Particular attention
      is given to the applications of NO to cardiovascular and hematological disorders.
      To this aim the authors examine the physiologic activities of NO and the
      mechanism of its antiplatelet, vasodilatory and antiproliferative action. Studies
      in animals and humans are also reported. Another section examines the drugs that
      increase the endogenous production of NO and modulate its activities. The last
      part is dedicated to the novel antithrombotic agent Nitroaspirin. Methods for NO
      detection will also be examined.

PMID- 15720225
TI  - Azimilide, a novel oral class III antiarrhythmic for both supraventricular and
      ventricular arrhythmias.
AB  - Azimilide is an investigational Class III antiarrhythmic that has been developed
      for treating both supraventricular and ventricular tachyarrhythmias. Similar to
      other Class III antiarrhythmics, azimilide prolongs myocardial repolarization in
      a dose-dependent manner by increasing the action potential duration, QT interval,
      and effective refractory period. The most frequent reported side effect is
      headache, with rare serious adverse events of early reversible neutropenia and
      Torsades de Pointes. In long-term follow up, the patient withdrawal rate has been
      low. Azimilide has very predictable pharmacokinetics, is predominantly
      hepatically metabolized, and has no significant drug interactions with digoxin or
      warfarin. In animal models, azimilide has been shown to be very effective in
      suppressing both atrial and ventricular tachyarrhythmias, decreasing the
      defibrillation energy requirement, and preventing post-myocardial infarction
      ventricular tachycardia and fibrillation. Clinically, in a series of 4 double
      blind, randomized, placebo-controlled trials, the Azimilide Supraventricular
      Arrhythmia Program which included over 1000 patients and approximately 70% with
      structural heart disease, azimilide showed a significant prolongation in the time
      to first recurrence of paroxysmal supraventricular tachycardia or atrial
      fibrillation/flutter. With respect to ventricular tachyarrhythmias, the AzimiLide
      post-Infarct surVival Evaluation Trial was a large randomized, multinational,
      prospective, placebo-controlled study in recent survivors of myocardial
      infarction at high risk for sudden cardiac death. After 1 year of follow-up, this
      study showed no statistical difference in all-cause mortality between placebo and
      azimilide. However, azimilide did statistically reduce the incidence of new
      atrial fibrillation. Further trials are necessary to evaluate the efficacy of
      azimilide in patients with symptomatic ventricular arrhythmias.

PMID- 15720226
TI  - Leukocyte P2 receptors: a novel target for anti-inflammatory and anti-tumor
      therapy.
AB  - P2 receptors are a class of plasma membrane receptors ligated by extracellular
      nucleotides and expressed ubiquitously throughout the body. Two main families are
      known: P2X and P2Y. P2X are ligand (ATP)-gated channels, while P2Y are G-protein
      coupled seven membrane-spanning receptors. The P2X and the P2Y subfamilies
      comprise seven and eight members, respectively. While ATP is the only known
      physiological ligand of P2X receptors, P2Y receptors are known to be also
      activated by ADP, UTP, UDP and UDP-glucose in a subtype-specific manner. Several
      P2 subtypes are expressed by leukocytes where they have been implicated in a host
      of different responses ranging from chemotaxis to differentiation, from
      proliferation to cytotoxicity, from secretion of inflammatory mediators to cell
      fusion. However, until recently there was no in vivo proof of the participation
      of P2 receptors in inflammatory or proliferative disorders and, in addition, few
      pharmacological modulators of P2 function were available. During the last two
      years animal and human studies have produced preliminary but nevertheless
      compelling evidence in support of an important function of P2 receptors in
      inflammation and hematological tumors. Importantly, selective blockers of these
      receptors have been synthesized, thus paving the way to the possible development
      of P2-targeted anti-inflammatory and anti-tumoral therapies.

PMID- 15720229
TI  - Involvement of mast cells in angiogenesis and chronic inflammation.
AB  - Mast cells (MC) are granulated secretory cells that have long been recognized as
      a rich source of biologically highly active mediators such as biogenic amines,
      prostaglandins, leukotrienes, proteases, cytokines and chemokines. Most of their
      biological functions however has been rather elusive. There are now emerging data
      assigning these cells a relevant role in orchestrating angiogenesis, both in
      normal and pathological conditions. MC indeed synthesize and release a large
      array of proangiogenic factors upon different stimulation pathways. In addition,
      MC have been recognized as key cells in mediating host innate and adaptive immune
      responses. This review summarizes the most recent acquisitions concerning MC
      involvement in angiogenic processes and chronic inflammatory reactions.

PMID- 15720228
TI  - Role of inflammatory mediators in angiogenesis.
AB  - The angiogenic process involves several cell types and mediators, which interact
      to establish a specific microenvironment suitable for the formation of new
      capillaries from pre-existing vessels. Angiogenesis occurs in several
      physiological and pathological conditions, such as embryo development and wound
      healing, diabetic retinopathy and tumours. Inflammatory cells, namely
      monocytes/macrophages, T lymphocytes and neutrophils, fully participate in the
      angiogenic process by secreting cytokines that may affect endothelial cell (EC)
      functions, including EC proliferation, migration and activation. Angiogenesis is
      the result of a net balance between the activities exerted by positive and
      negative regulators. With regards to inflammatory cells and endothelium cross
      talk, such balance is conceptually very similar to that of pro-inflammatory and
      anti-inflammatory mediators that modulate an appropriate inflammatory response.
      In this review we will mainly discuss the relevance of both physiological and
      pathological inflammatory processes in angiogenesis, with particular regards to
      microenvironmental contribution. We will also describe some of the most relevant
      pro-inflammatory cytokines in the modulation of the angiogenic process.
      Furthermore, we will concentrate on what has been recently reported about the
      mechanism by which some of these cytokines are induced during inflammation to
      promote a suitable microenvironment for angiogenesis and tumour progression. Pro
      angiogenic cytokines, such as IL-1 and TNF, and anti-angiogenic cytokines such as
      IFN-gamma and IL-12, will be briefly described. We will try to provide a
      rationale for the use of both cytokines and cytokine blockades as novel potential
      pharmaceutical targets to modulate angiogenesis in chronic inflammation as well
      as in cancer.

PMID- 15720230
TI  - Development of vasculature targeting strategies for the treatment of chronic
      inflammatory diseases.
AB  - The pathogenesis of a number of chronic inflammatory processes can be attributed
      to prolonged neovascularization. This article reviews recent studies on the
      vasculature targeting strategies for the treatment of chronic inflammatory
      diseases. Targeting of the vasculature of inflamed organs could underlie a new
      pharmacological approach in the treatment of inflammatory diseases by taking
      advantage of formulations that deliver drugs to blood vessels specifically
      located at disease sites and to inflammatory cells.

PMID- 15720231
TI  - CXC chemokines in angiogenesis relevant to chronic fibroproliferation.
AB  - The CXC chemokines are an unique family of cytokines known for their ability to
      behave in a disparate manner in the regulation of angiogenesis. The mechanisms
      for the different activity in regulating angiogenesis by members of this
      chemokine family is related to the following: 1) the presence or absence of the
      structural/functional motif (Glutamic acid-Leucine-Arginine; 'ELR' motif) that
      immediately precedes the first cysteine amino acid residue in the primary
      structure of these cytokines; 2) interferon-inducible gene expression; and 3)
      receptors that these chemokines use to mediate their biological activity. Members
      that contain the 'ELR' motif (ELR(+)) are potent promoters of angiogenesis, and
      mediate their angiogenic activity via binding and activating CXCR2 on
      endothelium. In contrast, members that are inducible by interferons and lack the
      ELR motif (ELR(-)) are potent inhibitors of angiogenesis, and bind to the
      alternatively splice variant of CXCR3, CXCR3B on endothelium. This review will
      discuss the biology of these angiogenic and angiostatic CXC chemokines, and
      discuss their disparate angiogenic activity in the context of a variety of
      chronic fibroproliferative disorders.

PMID- 15720232
TI  - Antiangiogenesis for rheumatoid arthritis.
AB  - Angiogenesis, i.e., the induction of new blood vessels from existing vasculature,
      is a crucial event in the formation and maintenance of the pannus in rheumatoid
      arthritis (RA). The arthritis is characterized by destruction of peripheral
      joints in which the cartilage and bone are destroyed by proliferative synovitis.
      This is characterized by infiltration of inflammatory cells and formation of new
      blood vessels. Angiogenesis occurs since the early stage of the disease, and
      supports progression of the arthritis. It has been demonstrated in animal models
      of arthritis that inhibition of angiogenesis reduces of the arthritis. This
      suggests that pharmacological inhibition of angiogenesis may play an important
      role in the treatment of RA. In particular, disruption of new blood vessels can
      not only prevent delivery of nutrients to the inflammatory site, but can also
      lead to vessel regression, hence reversal of disease. To sum up, since
      angiogenesis is central in maintaining of synovitis in RA, antiangiogenesis
      probably represents a therapeutic tool. This view is supported by recent studies
      in animal models of arthritis where antiangiogenic drugs deliver a therapeutic
      benefit.

PMID- 15720233
TI  - Inhibition of angiogenesis by non-steroidal anti-inflammatory drugs: from the
      bench to the bedside and back.
AB  - The formation of new blood vessels, a process globally referred to as
      angiogenesis, occurs in a number of pathological conditions, such as cancer and
      chronic inflammation. Recent findings indicate that cyclooxygenase-2 (COX-2), the
      inducible form of the cyclooxygenase (COX) isoenzymes, acts as a potent inducer
      of angiogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs) are classical
      inhibitors of COX enzymes, which are widely prescribed for the treatment of
      inflammation, pain and fever. Selective COX-2 inhibitors (COXIBs) have been
      subsequently developed with the purpose to improve the safety profile of this
      class of therapeutics. More recently, substantial preclinical evidence
      demonstrated that NSAIDS and COXIBs have anti-angiogenic properties. This newly
      recognized activity opens the possibility of using these drugs for the treatment
      of angiogenesis-dependent diseases. In this article we review the most recent
      advances in understanding the mechanisms by which NSAIDs and COXIBs suppress
      angiogenesis, and we discuss their potential clinical use as anti-angiogenic
      drugs.

PMID- 15720235
TI  - Biological therapies of autoimmune diseases.
AB  - The advances in the understanding of the pathogenesis of the autoimmune diseases
      have led to new treatment targets. Biological agents enhance or replace
      conventional immunosuppressive therapies in the treatment of autoimmune diseases.
      TNF-alpha has been validated as a good treatment target but the potential
      modalities also include the inhibition of the interaction between LFA-3
      (lymphocyte function-associated antigen 3) and CD2, the blockade of the IL-1
      receptors, the antibodies against the alpha4 integrins, the antibodies against B
      cell CD20 and the inhibition of the activation of T-cells. The new treatments
      have had a major impact on inflammatory symptoms, the radiological damage and the
      anemia of chronic disease in rheumatoid arthritis and have substantially
      controlled the signs and symptoms in the spondylarthropathies group and plaque
      type psoriasis. The efficacy of the biologic agents in systemic lupus
      erythematosus warrants further investigation but there have been some promising
      results in proliferative lupus nephritis. Several small studies have explored
      their use in the treatment of Sjogren's syndrome, adult onset Still's disease and
      several vasculitides but the results are still preliminary and warrant
      confirmation. The efficacy of the biological agents has been impressive.
      Susceptibility to infections has always been a major concern; a high level of
      suspicion is necessary and strategies should be implemented for the prevention,
      the rapid identification and pre-emptive therapy of such infections.

PMID- 15720236
TI  - Genetic heterogeneity of hepatitis viruses and its clinical significance.
AB  - The genetic heterogeneity of hepatitis B virus (HBV) (8 genotypes A-H) has been
      applied for tracing the route of HBV transmission and the geographical migration
      of HBV carriers but it also appeared to have clinical implications. The secondary
      structure of e encapsidation signal could explain why the precore mutant virus
      prevails in Mediterranean countries, where genotype D is most prevalent, while
      the wild type virus is frequent in Western countries, where genotype A is most
      prevalent. There is increasing evidence that patients infected with genotype C
      have more severe outcome of chronic liver disease than those infected with
      genotype B. Genotype B was associated with fulminant hepatitis and more severe
      episodes of acute exacerbation of chronic HBV infection. Patients infected with
      genotype B appeared to seroconvert earlier than those infected with genotype C.
      The hepatitis delta virus (HDV) has 3 genotypes (I, II, III) which are associated
      with different disease patterns. Genotype III is the most distantly related HDV
      genotype and is associated with the most severe outcome while genotype II with
      relatively mild liver disease. The most geographically widespread genotype is I
      and is associated with a broad spectrum of chronic liver disease. The hepatitis C
      virus (HCV) displays high genetic heterogeneity with six genotypes (1-6),
      multiple subtypes and quasispecies. This viral diversity has epidemiological and
      clinical implications and has been associated with the severity of liver disease,
      prognosis, response to treatment and failure to generate an effective protective
      vaccine. HCV genotype 1 is the predominant genotype in Western countries and has
      been associated with a low response rate to interferon-alpha (IFN-alpha) or to
      the combination of ribavirin and IFN-alpha. Consequently the duration of
      treatment has been tailored according to HCV genotype.

PMID- 15720237
TI  - Amyloidosis and auto-inflammatory syndromes.
AB  - Amyloidosis remains currently a severe potential complication of many chronic
      inflammatory disorders. It is not exactly know why some patients develop a
      progressive amyloidosis, whereas others do not although latent deposits may be
      present. A permanent acute phase response, ideally evaluated with serial
      measurement of serum protein SAA, the precursor of the AA protein deposited in
      tissues, seems to be a prerequisite to the development of inflammatory (AA)
      amyloidosis. Genetic factors have however been recently emphasized. Among
      persistent or emerging causes of AA amyloidosis, hereditary periodic fever
      syndromes also known as auto-inflammatory syndromes are a group of diseases
      characterised by intermittent bouts of clinical inflammation with focal organ
      involvement mainly: abdomen, musculoskeletal system and skin. The most frequent
      is familial Mediterranean fever which affects patients of Mediterranean descent
      all over the world. Three other types have been recently clinically as well as
      genetically characterised. A thorough diagnosis is warranted, as clinical and
      therapeutic management is specific for each of these diseases.

PMID- 15720238
TI  - Familial Mediterranean fever in the post-genomic era: how an ancient disease is
      providing new insights into inflammatory pathways.
AB  - Familial Mediterranean fever (FMF, MIM24900), described as a clinical entity only
      slightly over a half-century ago, has ancient roots among populations surrounding
      the Mediterranean basin. It is the most prevalent of the hereditary periodic
      fever syndromes, a group of disorders characterized by episodic attacks of fever
      and inflammation. Seven years ago, it was discovered that FMF is caused by
      mutations in MEFV, a gene that encodes a protein variously called pyrin or
      marenostrin. As exciting as that discovery was, physicians and patients alike
      were disappointed that the protein sequence of pyrin/marenostrin did not
      immediately suggest clues as to the molecular etiology of FMF. Though we are
      still far from a complete understanding of the function of pyrin/marenostrin at
      the cellular level, continued study of this intriguing protein is revealing new
      molecular details about inflammatory processes; the emerging information is
      relevant not only to FMF, but to innate immunity in general. Data from several
      laboratories demonstrate that pyrin/marenostrin is intimately connected to three
      important cellular pathways: apoptosis, cytoskeletal signaling and cytokine
      secretion. These connections occur, at least in part, through the direct
      interaction of the pyrin/marenostrin protein with two cytosolic protein adaptors:
      ASC (also called PyCARD or Tms1) and PSTPIP (also called CD2BP1). Here, we review
      the more recent literature regarding the molecular and cellular biology of
      pyrin/marenostrin and pinpoint open questions for future study.

PMID- 15720239
TI  - Molecular and genetic characteristics of hereditary autoinflammatory diseases.
AB  - Autoinflammatory diseases are defined as recurrent "unprovoked" inflammatory
      events which do not produce high-titer autoantibodies or antigen-specific T
      cells. There are currently eight hereditary forms of these diseases: Familial
      Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome
      (HIDS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS),
      Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS),
      chronic infantile neurologic cutaneous articular (CINCA) syndrome or neonatal
      onset multisystem inflammatory disease (NOMID), pyogenic sterile arthritis,
      pyoderma gangrenosum, acne (PAPA) and Blau syndrome. Apart from FMF (which has a
      prevalence of about 0.1 percent among non-Ashkenazi Jews, Armenians, Turks and
      Arabs), they are very rare disorders. FMF and HIDS are autosomal recessive
      diseases, all the other members of the family are autosomal and dominantly
      transmitted. Their common clinical features are recurrent and usually short
      attacks of synovitis and various skin eruptions; abdominal pain and fever are
      also frequently observed. The genes of all of these diseases have been discovered
      and, with the exception of HIDS, it was found that the proteins they encode share
      certain domains taking part in innate immunity and apoptosis. Thus it was evident
      that hereditary autoinflammatory diseases may help us understand better a number
      of important and prevalent pathologic events. We have reviewed the recent and
      rapidly accumulating knowledge on the molecular aspects of these disorders.

PMID- 15720240
TI  - Behcet's disease as an autoinflammatory disorder.
AB  - Autoinflammatory diseases are a group of heritable disorders that are
      characterized by seemingly unprovoked episodes of inflammation at certain
      locations and and relative lack of high-titer autoantibodies or antigen-specific
      T cells. Behcet's disease is an inflammatory disorder of unknown aetiology, and
      many of its characteristic recurrent manifestations overlap with those of
      autoinflammatory diseases. Behcet's disease has a complex genetic aetiology, and
      it is more prevalent in certain geographic regions and/or in particular ethnic
      groups. Enhanced inflammatory response and over-expression of proinflammatory
      cytokines are the prominent features of Behcet's disease, and they are compatible
      with the findings in other autoinflammatory disorders. There are also evidences
      of antigen-driven immune response in Behcet's disease, but it possibly develops
      on the background of enhanced innate immune reactivity. Delineation of the
      similarities of Behcet's disease to other hereditary autoinflammatory diseases
      may help to clarify its pathogenesis and also to identify the missing links in
      the shared inflammatory pathways.

PMID- 15720241
TI  - Oxidative stress in the molecular mechanism of pathogenesis at different diseased
      states of organism in clinics and experiment.
AB  - According to modern images and results of our observations the oxidative stress
      (OS) is a non-specific though certain component of pathogenesis at numerous
      diseased states of organism having in the basis the thoroughness of pathogenic
      disturbances of phospholipids (PL) metabolism and processes of their free radical
      oxidation (FRO), which takes place in the membrane formations of as the whole
      cell, as well as the mitochondrial and microsomal fractions (MCF and MSF) of the
      white rat brain, liver mitochondria, lung shadows, at the same time erythrocyte
      and lymphocyte shadows at brain acute edema, ischemia, reperfusion and
      desympathization, infarction of myocardium, tuberculosis of lungs, diabetes,
      Familial Mediterranean Fever (FMF), intoxications under halothane anaesthesia
      (HA) and with micotoxin zearalenon. The regularities observed promote to
      understand from the point of view of modern approaches the molecular mechanisms
      of initiation, development and generalization of factors for OS formation under
      pathologic conditions. It is more obvious at zearalenon intoxication with
      intensification of lipids FRO processes and failures in PL-PL ratio phenomena.
      The lymphocytes membranes of the white rats spleen subjected OS induced by
      zearalenon intoxication permit us conclude that the general immune status of the
      organism decreases. It is generally peculiar to the states under conditions of
      generalized intoxication. The observed increase of phospholipase A(2) activity
      induces the release of high concentrations of lysophosphatidylcholines (LPC) and
      non-etherified fatty acids (NEFA) of polyenic range with prevail of arachidonic
      acid as a pathogenic factor, namely, at modelling brain acute edema by
      tetraethylolovo to white rats. Formation of the above mentioned disturbances to
      some extent depends on hydrophobic properties of toxins, particularly,
      zearalenon. The latter gives certain tropism to dopamine-beta-monooxygenase
      (DBM), and ability to stimulate functional activity of the enzyme. Striking
      haemolytic properties of phospholipase A(2) induced by existence of LPC and NEFA
      high concentrations, and products of their peroxidation, promote elimination of
      separate protein fractions of erythrocyte membranes (EM) responsible for OS
      formation and decrease of erythrocytes resistance to peroxide hemolysis. Increase
      of DBM activity under the effect of relatively moderate doses of zearalenon (1-15
      microg/ml) is accompanied with extra intensification of catecholamine
      synthesizing function of the organism with lethal result. Data of publications
      represented testify exceptional efficiency of sodium thiosulfate (STS) as a
      powerful synergist for endogenous factors of antioxidant effect, particularly
      alpha-tocopherol (alpha-T), which is the main component for the system of cell
      antiradical defence. Detoxicating effect of STS can be demonstrated indeed on the
      example of zearalenon intoxication during the first two hours with the reduction
      of metabolism disturbances of PL and products of its peroxidation. Comparative
      evaluation of molecular mechanisms of STS normalizing effect as a supplier for
      hydrogen and sulphur ions, as well as an effective synergist for alpha-T on the
      level of various formations of the live cell in compare with the effects of alpha
      T and ubiquinone, allowed to make a special accent on the role of STS in
      interaction with energy-dependent enzymatic systems of cell antiradical defence,
      as well as accumulation and transformation of energy on the level of
      mitochondrial membranes. The results obtained by us confirm a number of clinical
      experimental observations, which demonstrate treatment and prophylactic role of
      STS at different pathologic states of the organism. STS protectory role at toxic
      injuries of the organism is higher at its preliminary introduction to the
      organism before modelling of the studied diseased states, especially at
      zearalenon and halothane (H) intoxication (in the last case before HA). These
      data serve a sound affirmation for protectory function of STS, detailed
      revelation of molecular properties of pathogenesis of the studied intoxication to
      which a part of our clinical and experimental studies at present is devoted.

PMID- 15720242
TI  - The role of infections in the pathogenesis of autoimmune diseases.
AB  - The autoimmune diseases result from inappropriate responses of the immune system
      to self antigens. The etiology of autoimmune diseases remains largely unknown but
      candidate etiologic factors include genetic abnormalities and infections.
      Although there are considerable data supporting the role of infections in a
      variety of autoimmune diseases, this role has been unequivocally established in
      only a few autoimmune diseases. The difficulty in establishing the infectious
      etiology of autoimmune diseases stems from several factors such as the
      heterogeneity of clinical manifestations in individual autoimmune diseases and
      the time interval between infection and autoimmune disease. The data on this
      association derive from clinical observations, epidemiological studies and
      research using laboratory techniques, protein sequence database screening and
      animal models. Infectious agents can cause autoimmune diseases by different
      mechanisms, which fall into two categories: antigen specific in which pathogen
      products or elements have a central role e.g. superantigens or epitope
      (molecular) mimicry, and antigen non-specific in which the pathogen provides the
      appropriate inflammatory setting for "bystander activation". The most important
      mechanisms are molecular mimicry and superantigens. As far as molecular mimicry
      is concerned the recent data on the degeneracy of T cell recognition shifted the
      focus from searching for linear sequence homology to looking for similarity of
      antigenic surfaces. Special mention has to be made to retroviruses as they have
      some unique means of inducing autoimmunity.

PMID- 15720243
TI  - MEFV mutation carriers and diseases other than familial Mediterranean fever:
      proved and non-proved associations; putative biological advantage.
AB  - Vasculitis is definitely associated with familial Mediterranean fever. This
      familial Mediterranean fever-associated vasculitis takes one of three forms:
      polyarteritis nodosa, with or without microscopic polyangiitis, and Henoch
      Schonlein purpura. Behcet disease and inflammatory bowel diseases may also be
      associated with familial Mediterranean fever, though this is yet to be formally
      proven. The selective biological advantage, if any, for carriers of simple
      heterozygotic mutations in the gene responsible for familial Mediterranean fever,
      MEFV, is not known. Indirect arguments are given for a better defense against
      certain groups of bacterial pathogens and amongst intra-cellular bacteria,
      Mycobacterium tuberculosis.

PMID- 15720244
TI  - Molecular study of FMF patients in Armenia.
AB  - Familial Mediterranean Fever (FMF, MIM 249100), or Periodic disease, is a
      recessively transmitted and ethnically restricted condition prevalent in
      population from the Mediterranean decent. FMF notoriously has been hard to
      diagnose until mutations in the MEFV gene have been identified and as a
      tremendous help are used for the diagnosis of difficult cases. Since FMF can be
      controlled by medication, it is extremely desirable to have a firm diagnosis. The
      aim of this study was to establish the frequency of the most common mutations and
      genotypes in Armenian population. Molecular analysis of MEFV gene mutations in
      3000 Armenian patients has demonstrated direct correlation between the clinical
      severity and the molecular diagnostic criteria of the disease, including the
      development of renal amyloidosis with MEFV genotypes. MEFV genotyping performed
      in the framework of a genetic counseling may reveal and identify affected
      individuals in presymptomatic phase, providing the possibility of a precocious
      start of the therapy.

PMID- 15720245
TI  - Pharmacological and clinical basis of treatment of Familial Mediterranean Fever
      (FMF) with colchicine or analogues: an update.
AB  - Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is
      characterised by recurrent attacks of fever and serositis, lasting 24-72 hours.
      Since 1972 colchicine has become the drug of choice for prophylaxis against FMF
      attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is
      absorbed in the jejunum and ileum. It metabolised by liver and only small amounts
      are recovered unchanged in the urine. Really plasma half-life is prolonged in
      patients with liver or renal failure. Colchicine is able to prevent activation of
      neutrophils, binding beta-tubulin and making beta-tubulin-colchicine complexes;
      this way inhibits assembly of microtubules and mitotic spindle formation;
      moreover its mode of action includes modulation of chemokines, prostanoids
      production, inhibition of neutrophil and endothelial cell adhesion molecules. The
      minimal daily dose in adults is 1.0 mg/die, but in children there is not a
      definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug
      might interfere with male and female fertility and with children growth, but,
      according to current guidelines and because of rare side effects of the drug, FMF
      patients are recommended to take colchicine. Since colchicine treatment is often
      complicated by frequent gastrointestinal side effects, by our experience, in
      order to improve colchicine tolerance we recommend: lactose-free diet and
      treatment of intestinal bacterial overgrowth and/or Hp-infection, assessed by
      breath tests. Since our data showed that 10-15% of FMF patients seem are non
      responders or intolerant to colchicine, today we are working in the design of
      colchicine analogues which may have lesser toxicities and a larger therapeutic
      window.

PMID- 15720246
TI  - Complement: an inflammatory pathway fulfilling multiple roles at the interface of
      innate immunity and development.
AB  - Complement has been long perceived as an innate immune system that plays a
      pivotal role in the maintenance of host defense against infectious agents and the
      propagation of pro-inflammatory responses in the context of human disease.
      Complement activation has been associated with the onset of acute inflammatory
      reactions leading to complications such as acute graft rejection, local tissue
      injury and multi-organ failure. However, recent studies have indicated that
      various complement activation products may exert a beneficial effect by
      contributing to critical developmental and regenerative processes. Appreciating
      this extraordinary 'versatility' of complement proteins provides a framework for
      revisiting the design of effective complement therapeutics. A balanced strategy
      will have to consider limiting the detrimental proinflammatory effects of
      complement while preserving those activities that promote tissue repair and
      regeneration, cell survival and early development.

PMID- 15720248
TI  - Pathogenetics of the human SLC26 transporters.
AB  - Over the past decade, 11 human genes belonging to the solute linked carrier (SLC)
      26 family of transporters, have been identified. The SLC26 proteins, which
      include SAT-1, DTDST, DRA/CLD, pendrin, prestin, PAT-1/CFEX and Tat-1, are
      structurally related and have been shown to transport one or more of the
      following substrates: sulfate, chloride, bicarbonate, iodide, oxalate, formate,
      hydroxyl or fructose. Special interest has focused on four members of the SLC26
      family that are associated with distinct recessive diseases: (i) Mutations in
      SLC26A2 lead to four different chondrodysplasias (diastrophic dysplasia,
      atelosteogenesis type II, achondrogenesis type IB and multiple epiphyseal
      dysplasia); (ii) SLC26A3 is associated with congenital chloride diarrhea; (iii)
      SLC26A4 is associated with Pendred syndrome and non-syndromic deafness, DFNB4;
      and (iv) SLC26A5 is defective in non-syndromic hearing impairment. This review
      article summarizes current information on the pathophysiological consequences of
      mutations in the human SLC26A2 to A5 genes.

PMID- 15720247
TI  - Treatment of H. pylori infection: a review.
AB  - Helicobacter pylori infection has been indicated as the main pathogenic factor in
      the development of chronic gastritis, peptic ulcer disease, and gastric
      malignancies. Although the vast majority of infected subjects do not carry but a
      mild, asymptomatic gastritis, still there are some cases in which the eradication
      of the infection appears mandatory. This review addresses current anti
      Helicobacter regimens and pharmacological resources, and highlights the pros and
      cons of each of them, according to the most recent and reliable clinical trials.
      Also, basic recommendations are given, regarding treatment choice in the event of
      the failure of a first or second line eradicating strategy, and about the
      implementation of standard regimens with newer antibacterial devices as
      probiotics.

PMID- 15720249
TI  - Modulators of the coagulation cascade: focus and recent advances in inhibitors of
      tissue factor, factor VIIa and their complex.
AB  - Recent developments in the field of haemostasis and thrombosis highlighted the
      crucial role of the tissue factor/factor VIIa complex (TF/FVIIa) in the
      initiation of coagulation processes. Nowadays, anticoagulant therapies involving
      heparin or coumarin derivatives, thrombin or factor Xa inhibitors are generally
      associated with side effects such as bleeding and thrombocytopenia. In this
      context, the inhibition of TF, FVIIa and their complex by efficient
      antithrombotic drugs represents a new strategy to reduce this bleeding and to
      prevent thrombosis events. Moreover, TF/FVIIa inhibition is shown to be useful in
      the treatment of biological processes independent of the clotting cascade such as
      angiogenesis and cancer. Among the natural and genetically engineered TF/FVIIa
      inhibitors, injections of the recombinant protein rNAPc2 show clinical
      improvements, such as reduced bleeding and thromboembolism, over classical drugs
      used in the therapy of coronary angioplasty and hip or knee replacement surgery.
      The knowledge of the 3D-structure of TF/FVIIa complex and examination of co
      crystal data of some drugs bound to this complex led to the design and synthesis
      of numerous TF/FVIIa inhibitors. Among them, the p-amidinophenylurea 18 (Ki =
      0.027 microM), the pyrimidinones PHA-927 (30, IC50 = 0.016 microM) and PHA-798
      (31, IC50 = 0.014 microM) and the pyridinone 37 (IC50 = 0.052 microM) are highly
      potent inhibitors of the TF/FVIIa complex, deprived of activity towards thrombin
      (IC50 > 30-100 microM) and factor Xa (IC50 > 10-100 microM), other proteases
      involved in the coagulation cascade. Both pyrimidinones prevent arterial
      thrombosis in non-human primate models of thrombosis and represent a safe
      approach to anti-thrombotic therapy in patients with cardiovascular risk factors.

PMID- 15720250
TI  - New aminocoumarin antibiotics from genetically engineered Streptomyces strains.
AB  - The aminocoumarin antibiotics novobiocin, clorobiocin and coumermycin A(1) are
      produced by different Streptomyces strains and are potent inhibitors of DNA
      gyrase. The biosynthetic gene clusters of all three antibiotics have been cloned
      and sequenced, and the function of most genes contained therein has been
      elucidated. In the last years, a number of "unnatural" aminocoumarins could be
      generated using the genetic information for the biosynthesis of these
      antibiotics. The investigated enzymes of aminocoumarin biosynthesis have less
      than-perfect substrate specificity, facilitating the production of new
      antibiotics by various methods. Several new aminocoumarins could be produced by
      targeted genetic manipulation in the natural producers, but also in heterologous
      host Streptomyces coelicolor after expression of the respective gene cluster.
      Mutasynthesis experiments, i. e. generation of a cloQ-defective mutant of the
      clorobiocin producer and feeding of 13 different structural analogs of 3
      dimethylallyl-4-hydroxybenzoic acid to this mutant, allowed the isolation of 32
      new aminocoumarins. These compounds contained, instead of the genuine 3
      dimethylallyl-4-hydroxybenzoyl moiety, the externally added analogs as the acyl
      components in their structures. Production of new aminocoumarins was also
      achieved by chemoenzymatic synthesis in vitro. Several biosynthetic enzymes have
      been heterologously expressed, purified und used for chemoenzymatic synthesis.
      The structures of the new aminocoumarins were elucidated by NMR and mass
      spectroscopy. Their inhibitory activity on gyrase in vitro as well as their
      antibacterial activity was determined. These results give further insight into
      the structure-activity relationships of aminocoumarins.

PMID- 15720251
TI  - Alterations of mitochondrial DNA in common diseases and disease states: aging,
      neurodegeneration, heart failure, diabetes, and cancer.
AB  - It has long been considered that mitochondrial DNA disease is a rare genetic
      disorder causing neuromyopathy. However, alterations of mitochondrial DNA
      recently have been recognized to play an important role in the pathogenesis of so
      called common diseases such as heart failure, diabetes, and cancer. Although some
      of these alterations are inherited, more and more attention is being focused on
      the accumulation of mitochondrial DNA mutations in somatic cells, particularly
      terminally differentiated cells such as cardiomyocytes and neurons that occurs
      with age. Mitochondrial DNA is more vulnerable to alteration than nuclear DNA,
      mainly for two reasons. First, mitochondria are a major source of intracellular
      reactive oxygen species (ROS). Therefore mitochondrial DNA is under much stronger
      oxidative stress than is nuclear DNA. Second, mitochondria have a matrix-side
      negative membrane potential for oxidative phosphorylation. This membrane
      potential concentrates lipophilic cations inside mitochondria up to approximately
      1,000-fold. Unfortunately, some therapeutic reagents are lipophilic cations, and
      such exogenously added chemicals are prone to damage mitochondria. AZT, an anti
      HIV drug, causes mitochondrial myopathy as a side effect, which is a typical
      example of how chemotherapeutics adversely affect metabolism of mitochondrial
      DNA. In this review, we focus on ROS and chemical damage of mitochondrial DNA in
      common diseases.

PMID- 15720252
TI  - Peripheral arterial disease: a missed opportunity to administer statins so as to
      reduce cardiac morbidity and mortality.
AB  - Peripheral arterial disease (PAD) is a common condition associated with an
      increased risk of coronary heart disease, myocardial infarction and stroke. It
      follows that PAD merits aggressive preventive treatment that includes lipid
      lowering drugs (mainly statins). This review summarises the current knowledge
      concerning the use and mechanisms of action of statins in patients with PAD.
      Statins not only lower the risk of vascular events, but they also improve the
      symptoms associated with PAD. There is also evidence that statins reduce surgical
      mortality and improve graft patency and limb salvage. Because of the high risk, a
      more aggressive goal [i.e. low density lipoprotein cholesterol (LDL-C) of 70
      mg/dl; 1.8 mmol/l] [National Cholesterol Education Program (NCEP) Adult Treatment
      Panel III (ATP III), revised guidelines 2004] should be considered to maximally
      reduce the atheroma burden and related events. Not all statins can achieve this
      LDL-C target. Furthermore, there may be a need to use an additional lipid
      lowering drug so as to achieve the LDL-C goal and benefit from the different
      modes of action. Statins exert beneficial pleiotropic effects on haemostasis, the
      vasculature and inflammatory markers. There is also evidence that statins improve
      renal function (the plasma creatinine level is considered as an emerging vascular
      risk factor). Since PAD patients often take several drugs, there is a need to
      carefully consider their selection so as to maximize benefits and minimize
      adverse effects. Patients with PAD often do not receive adequate lipid lowering
      treatment. This situation needs to change.

PMID- 15720253
TI  - Recent developments on KCNQ potassium channel openers.
AB  - During the past five years, several members of the KCNQ potassium channel gene
      family have been identified with a high degree of CNS specificity. Within the
      KCNQ family, the combination of the KCNQ2/KCNQ3 proteins, and the KCNQ5/KCNQ3
      arrangement has been identified as the molecular correlates of the different M
      currents. Several lines of evidence are emerging demonstrating the importance of
      these channels in regulating neuronal excitability; for example, determination of
      the excitability threshold, firing properties, and responsiveness of neurons to
      synaptic inputs. Recent studies have shown that KCNQ openers have potential for
      the treatment of several CNS disorders characterized by neuronal
      hyperexcitability, such as migraine, epilepsy and neuropathic pain. This article
      reviews the recent developments of KCNQ potassium channel openers.

PMID- 15720254
TI  - Biorational approaches for insect control by enzymatic inhibition.
AB  - Conventional insecticides are highly toxic to many living organisms as well as to
      the environment; consequently, new biorational and more specific approaches to
      pest control have been developed. In this paper, we present an update of those
      approaches resulting from studies on inhibition of enzymes involved in key
      processes of insects life, particularly growth, molting and development of larvae
      and intraspecific communication of adults. The enzymes covered include pheromone
      degrading enzymes, pheromone biosynthetic enzymes, oxidoreductases, juvenile
      hormones, juvenile hormone epoxide hydrolases, proteases, molting hormones and
      phenoloxidases. Although these approaches refer to control of insect pests, many
      of them can be in principle also considered suitable for medicinal chemistry
      studies, since the mechanism of action of these inhibitors on related enzymes is
      quite similar, if not equal, in both fields.

PMID- 15720255
TI  - Conformationally restricted peptides as tools in opioid receptor studies.
AB  - The discovery of endogenous opioid peptides with their limited receptor
      selectivity more than two decades ago implicated their involvement in analgesia
      and initiated efforts to understand the molecular mechanisms underlying their
      action. Opioid peptides mediate their physiological and pharmacological effects
      through three major opioid receptor types (mu, delta, kappa), but the role of
      each of these receptors is not easy to distinguish. There has therefore, been an
      increasing need for potent and selective agonists and antagonists in this area.
      The incorporation of conformational constraints into analogs of biologically
      active peptides is a well-known approach for enhancing receptor selectivity and
      modulating efficacy. Conformational restriction has proven a valuable means for
      assessing disparities between the peptide binding characteristics at each of the
      opioid receptor types, since peptide analogs designed with appropriate
      conformational constraints possess the ability to adopt the conformation required
      for interaction at one receptor type but not another. In efforts to obtain better
      conformational integrity various conformationally restricted analogs of
      endogenous opioid peptides have been developed. In this paper we review the
      development of opioid analogs whose conformation was restricted either globally
      through different types of cyclization (such as amide bond formation, disulfide
      and monosulfide bridges, carbonyl and amine bridges) or locally, through
      incorporation of side-chain conformational constraints at a specific amino acid
      residue by synthesizing cyclic amino acids or constraining torsion angles by
      suitable substitutions. These two approaches have led to the development of
      potent and very selective agonists and antagonists at all three opioid receptor
      types.

PMID- 15720256
TI  - Chalcones: an update on cytotoxic and chemoprotective properties.
AB  - Chalcone is a unique template that is associated with several biological
      activities. In this review, an update of the cytotoxic and chemoprotective
      activities of chalcones is provided. Cytotoxicity against tumour cell lines may
      be the result of disruption of the cell cycle, inhibition of angiogenesis,
      interference with p53-MDM2 interaction, mitochondrial uncoupling or induction of
      apoptosis. Structural requirements for cytotoxic activity vary according to the
      mechanisms of action. For anti-mitotic activity, the presence of methoxy
      substituents, alpha-methylation of the enone moiety and the presence of 2'
      oxygenated substituents are favourable features. Conformational restraint of the
      chalcone template generally leads to a decrease in cytotoxic activity.
      Chemoprotection by chalcones may be a consequence of their antioxidant
      properties, mediated via inhibition or induction of metabolic enzymes, by an anti
      invasive effect or a reduction in nitric oxide production. Hydroxyl and prenyl
      substituents are associated with antioxidant properties and induction of quinone
      reductase activities. The thiol reactivity of chalcones is likely to contribute
      to both cytotoxic and chemoprotective properties of these compounds.

PMID- 15720257
TI  - The impact of tumor physiology on camptothecin-based drug development.
AB  - The genomic era has shifted anticancer drug development from its traditional mode
      concentrated on natural product cytotoxic agents to mechanism-based drug design
      focused on signal transduction pathways. Yet traditional cytotoxic chemotherapies
      continue to have an important role in the armamentarium. This is particularly
      true when one considers that important elements of solid tumor physiology -
      acidosis and hypoxia - have rarely been incorporated into algorithms for
      anticancer drug development. It is now well established that a majority of solid
      tumors exist in an acidic and hypoxic microenvironment that promotes resistance
      to radiation and chemotherapies apart from any drug-induced target mutations or
      efflux protein pumps. The acidic extracellular environment leads to a pH gradient
      unique to tumor cells. This gradient will favor uptake and retention of small
      molecule drugs that are weak acids. The converse is true for weak bases. The
      camptothecin class of topoisomerase I inhibitors is one example of a natural
      product cytotoxic that can exploit the tumor pH gradient. Screening of compounds
      based on selective activity at acidic pH (pH modulation), rather than potency,
      reveals analogs that are over ten times more active under the acidic conditions
      prevalent in vivo. Thus, knowledge of the tumor metabolic phenotype gained at the
      beginning of the 20(th) century can lead to more effective anticancer drugs in
      the new millennium.

PMID- 15720258
TI  - Cisplatin resistance and transcription factors.
AB  - Cisplatin is one of the most potent and widely used anti-cancer agents in the
      treatment of various solid tumors. However, the development of resistance to
      cisplatin is a major obstacle in clinical treatment. Several mechanisms are
      thought to be involved in cisplatin resistance, including decreased intracellular
      drug accumulation, increased levels of cellular thiols, increased nucleotide
      excision-repair activity and decreased mismatch-repair activity. In general, the
      molecules responsible for each mechanism are upregulated in cisplatin-resistant
      cells; this indicates that the transcription factors activated in response to
      cisplatin might play crucial roles in drug resistance. It is known that the tumor
      suppressor proteins p53 and p73, and the oncoprotein c-Myc, which function as
      transcription factors, influence cellular sensitivity to cisplatin. So far, we
      have identified several transcription factors involved in cisplatin resistance,
      including Y-box binding protein-1 (YB-1), CCAAT-binding transcription factor 2
      (CTF2), activating transcription factor 4 (ATF4), zinc-finger factor 143 (ZNF143)
      and mitochondrial transcription factor A (mtTFA). Two of these-YB-1 and ZNF143
      lack the high-mobility group (HMG) domain and can bind preferentially to
      cisplatin-modified DNA in addition to HMG domain proteins or DNA repair proteins,
      indicating that these transcription factors may also participate in DNA repair.
      In this review, we summarize the mechanisms of cisplatin resistance and focus on
      transcription factors involved in the genomic response to cisplatin.

PMID- 15720259
TI  - Synthetic and natural coumarins as cytotoxic agents.
AB  - Coumarins, an old class of compounds, are naturally occurring benzopyrene
      derivatives. A lot of coumarins have been identified from natural sources,
      especially green plants. The pharmacological and biochemical properties and
      therapeutic applications of simple coumarins depend upon the pattern of
      substitution. Coumarins have attracted intense interest in recent years because
      of their diverse pharmacological properties. Among these properties, their
      cytotoxic effects were most extensively examined. In this review, their broad
      range of effects on the tumors as shown by various in vitro and in vivo
      experiments and clinical studies are discussed. Hence, these cytotoxic coumarins
      represent an exploitable source of new anticancer agents, which might also help
      addressing side-toxicity and resistance phenomena. These natural compounds have
      served as valuable leads for further design and synthesis of more active
      analogues. In this review, plant derived coumarins and their synthetic analogues
      were systematically evaluated based on their plant origin, structure-activity
      relationship and anticancer efficacy. Owing the their diverse effects and
      inconclusive results from different in vitro studies, the mechanism of their
      action is not yet fully understood and correlation of effects with chemical
      structures is not conclusive at the moment. It is the objective of this review to
      summarize experimental data for different coumarins, used as cytotoxic agents,
      because promising data have been reported for a series of these agents. Yet, the
      results from different coumarins with various tumor lines are contradictory in
      part. We therefore conclude that there is still a long way to go until we know
      which cytotoxic agent will clinically be suitable for what tumor entity for
      treatment. Their ability to bind metal ions represents an additional means of
      modulating their pharmacological responses.

PMID- 15720260
TI  - Chemical aspects of coumarin compounds for the prevention of hepatocellular
      carcinomas.
AB  - The normalization of plasma alanine aminotransferase (ALT) has been proved to be
      a strategy for preventing the development of hepatocellular carcinoma (HCC) in
      hepatitis C virus (HCV)-infection. Glycyrrhizin, a plant medicine, normalizes
      plasma ALT and prevents HCC. However, glycyrrhizin is administered intravenously
      and thereby chemical which is effective on oral administration is required.
      Coumarin compounds are active components of herbs used for the treatment of
      various diseases. The ability of coumarin compounds to lower plasma ALT were
      examined using mice concanavalin A-induced hepatitis and mice anti-Fas antibody
      induced hepatitis. Furanocoumarins pd-Ia, pd-II and pd-III lower plasma ALT, but
      they are large molecules that are hardly absorbed on oral administration.
      Furocoumarin effectively lowers plasma ALT, but the safety range between the
      effective and toxic dosages is narrow. In contrast, osthole, a simple coumarin,
      causes strong reduction of plasma ALT and also inhibits caspase-3 activation.
      Furthermore, this chemical is quite safe upon large dose administration. In the
      structure of osthole, the methoxy group at position-7 and the 3-methyl-2-butenyl
      group at position-8 were elucidated to be essential for the beneficial effect of
      this chemical. We conclude that osthole will become a leading chemical for
      synthesizing a compound which prevents HCC on oral administration.

PMID- 15720261
TI  - Novel anticancer targets and drug discovery in post genomic age.
AB  - Cancer is a serious disease with a complex pathogenesis, which threats human life
      greatly. Currently, great efforts have been put to the identification of novel
      anticancer targets and the discovery of anticancer drugs following the progress
      of chemogenomics, which will be reviewed briefly in this article. Furthermore,
      during the past 5 years, the global effort of sequencing human genome has
      provided us with an enormous number of potential targets associated with cancer
      therapy. As a result, the New Drug Discovery (NDD) is undergoing a transition
      "from gene to drug". Accordingly, the targets for anticancer drugs studies now
      are focused on some biological macromolecular targets associated with cancer and
      several interactive mechanisms involved in the growth and metastasis of cancer
      cells as well as tumor angiogenesis, such as Matrix Metalloproteinases (MMPs),
      Aminopeptidase N (APN), Tyrosine Kinase (TK), Farnesyltransferase (FTase) and
      cell Signal Transduction Pathway and so forth. Among these targets the MMP-2, -9
      and APN are the most extensively studied enzymes in our laboratory. The
      peptidomimetics Matrix Metalloproteinase Inhibitors (MMPIs) and APN inhibitors
      (APNIs) with the molecular scaffold of pyrrolidine, 3-amino-2-hydroxy-4-phenyl
      butyric acid (AHPA) and glutamylide, which have been designed and synthesized in
      our laboratory, will be described in the review, among which the pyrrolidine
      scaffold is patented with the IC(50) ranging from 1 nM to 300 nM against MMP-2,
      and MMP-9.

PMID- 15720262
TI  - Targeting microtubules for cancer chemotherapy.
AB  - Chemical compounds that interfere with microtubules such as the vinca alkaloids
      and taxanes are important chemotherapeutic agents for the treatment of cancer. As
      our knowledge of microtubule-targeting drugs increases, we realize that the
      mechanism underlying the anti-cancer activity of these agents may mainly lie in
      their inhibitory effects on spindle microtubule dynamics, rather than in their
      effects on microtubule polymer mass. There is increasing evidence showing that
      even minor alteration of microtubule dynamics can engage the spindle checkpoint,
      arresting cell cycle progression at mitosis and eventually leading to apoptotic
      cell death. The effectiveness of microtubule-targeting drugs for cancer therapy
      has been impaired by various side effects, notably neurological and hematological
      toxicities. Drug resistance is another notorious factor that thwarts the
      effectiveness of these agents, as with many other cancer chemotherapeutics.
      Several new microtubule-targeting agents have shown potent activity against the
      proliferation of various cancer cells, including cells that display resistance to
      the existing microtubule-targeting drugs. Continued investigation of the
      mechanisms of action of microtubule-targeting drugs, development and discovery of
      new drugs, and exploring new treatment strategies that reduce side effects and
      circumvent drug resistance may provide more effective therapeutic options for
      cancer patients.

PMID- 15720265
TI  - The transcriptome in blood: challenges and solutions for robust expression
      profiling.
AB  - Peripheral blood may be the most feasible tissue source in clinical assessment of
      differences in gene expression between diseases and drug treatments due to
      accessibility. Yet, gene expression profiling from blood remains a challenge.
      Blood is a complicated biological system consisting of a variety of cell types at
      different stages of development. In addition, blood is also one of the most
      variable tissue types for gene expression analysis. The success of a blood
      microarray study depends on the choice of cell isolation method and preparation
      technique. In this review, we give a brief overview of the current status of
      using blood as a source for expression profiling and discuss potential
      applications of this method in the practices of clinical research.

PMID- 15720263
TI  - Chemoresistance in non-small cell lung cancer.
AB  - The treatment of advanced non-small-cell lung cancer (NSCLC is based on the
      combination of platin and one of the following agents: taxanes, gemcitabine,
      vinorelbine or irinotecan. There are no significant differences in efficacy among
      these combinations suggesting that the maximum efficacy has been reached. In this
      review, we will consider the mechanisms of chemoresistance of the five groups of
      cytotoxic drugs commonly used in the treatment of advanced NSCLC as well as the
      clinical studies which have assessed the value of chemoresistance markers. Breast
      Cancer Related Protein (BRCP) expression has been related to irinotecan and
      cisplatin (CDDP) resistance. DNA repair capacity influences response to CDDP and
      ERCC1 gene stands out as a predictive marker of CDDP sensitivity. Preliminary
      studies indicate that high tubulin III and stathmin mRNA levels correlate with
      response to paclitaxel and vinorelbine and that high expression of class III
      tubulin by tumor cells assessed immunohistochemically in patients receiving a
      taxane-based regimen is associated with a poor response to chemotherapy, and a
      shorter progression-free survival. High expression levels of ribonucleotide
      reductase has also been related to response to gemcitabine. Uridine diphosphate
      glucuronosyltransferase isoform 1A1 (UGT1A1) genotype has been reported to be
      associated with time to progression and survival in patients treated with
      irinotecan. These data suggest that pharmacogenomic strategies may be used for
      developing customized chemotherapy in prospective studies. Adjuvant chemotherapy
      which had recently shown its usefulness in limited lung cancer represents another
      area of investigation for pharmacogenomic studies.

PMID- 15720266
TI  - Pathway and ontology analysis: emerging approaches connecting transcriptome data
      and clinical endpoints.
AB  - The increasing use of gene expression profiling offers great promise in clinical
      research into disease biology and its treatment. Along with the ability to
      measure changing expression levels in thousands of genes at once, comes the
      challenge of analyzing and interpreting the vast sets of data generated. Analysis
      tools are evolving rapidly to meet such challenges. The next step is to interpret
      observed changes in terms of the biological properties or relationships
      underlying them. One powerful approach is to make associations between the genes
      that are under investigation and well-known biochemical or signaling pathways,
      and further to assess the significance of such associations. Similarly, genes can
      be mapped to standardized biological categories via an ontology resource. We
      discuss these approaches and several web-based resources and tools designed to
      facilitate such analyses. This information can be used to facilitate
      understanding and to help design more focused experiments for validating the
      relevance and importance of these biological pathways and processes in human
      disease and therapeutics.

PMID- 15720267
TI  - Ethical and legal aspects of applied genomic technologies: practical solutions.
AB  - Many ethical and legal issues surround genomic technologies, some of which are
      present for other kinds of medical data, but some of which are specific to
      genomic data. Specifically the global nature of genomic data and the life-long
      implications of genetic defects on the health of the individual subject produce
      challenges in the ethical and legal handling of this data. In general, data
      derived from transcriptome analysis, which studies gene expression, as well as
      proteomics and metabolomics, carry less ethically-charged information than
      measures of the germ line genome. However, theoretical issues that have been
      raised related to withholding therapy based on a specific genotype which could
      also apply to a specific expression profile. Potential solutions for these
      challenges are discussed, such as maintaining a connection with research
      participants through a trusted third party, using electronic means to manage that
      contact and reconsent subjects. A flexible, secure information technology
      infrastructure is proposed to manage and search consent forms, provide the
      ability to collect additional data and consent while maintaining participant
      confidentiality.

PMID- 15720268
TI  - From traditional biomarkers to transcriptome analysis in drug development.
AB  - Traditional biomarkers have played an important role in drug development as well
      as patient care. A single traditional biomarker or surrogate endpoint is unlikely
      to either characterize the complete pathophysiology of a complex disease or
      capture all the therapeutic benefits or potential adverse effects that a drug
      will have in a diverse patient population. Transciptome analysis, on the other
      hand, can provide a large-scale survey of gene expression associated with the
      etiology of a human disease or pharmacological responses to a therapeutic
      intervention. The quantitative and qualitative readouts can provide increased
      power to identify novel drug targets or biomarkers indicative of drug safety or
      efficacy. Transcriptomics has positively impacted drug development and will
      continue to improve the medicines of the future. Here, we describe the
      increasingly important roles that traditional biomarkers and transcriptome
      analysis have played in various phases of drug discovery and development as well
      as the opportunities and challenges that they present to the pharmaceutical
      industry.

PMID- 15720269
TI  - The agony and ecstasy of "OMIC" technologies in drug development.
AB  - Over the last decade we have witnessed a fundamental change in how biomedical
      research is carried out and we can now assess the impact of the Human Genome
      Project on drug discovery and development. Advances in "omics" technologies
      (genomics, transcriptomics, proteomics and metabonomics) were touted as having
      the potential to revolutionize our approach to disease diagnosis, prognostication
      and development of novel therapeutics. However, the promise of rapid advances in
      medicine "from the lab bench to the bedside" has not manifested as of yet. Indeed
      it appears that the translational applications of genomic-based research have
      preceded the development of both (i) a conceptual framework for disease
      understanding and (ii) effective tools that can exploit the vast amounts of data
      derived from these efforts. In reality great progress has been made, however
      understanding processes such as disease progression (or drug response) requires
      systematic insight into dynamic (and temporal) differences in gene regulation,
      interaction and function. This review will discuss "omic" technologies with the
      emphasis upon advances in our understanding of the human genome derived
      transcriptome (RNA), and its proteome (proteins), while focusing upon the
      translation of this information into the drug development paradigm.

PMID- 15720270
TI  - The role of transcriptome analysis in pre-clinical toxicology.
AB  - A major benefit of the genomics revolution in biomedical research has been the
      establishment of transcriptome analysis as an enabling technology in the drug
      development process. Nowhere in the realm of drug development has the expectation
      of the impact of transcriptome analysis been greater than in the area of pre
      clinical toxicology. Transcriptome analysis, along with other new high-content
      data generating technologies, has the potential to radically improve the drug
      safety assessment process by allowing drug development teams to identify
      potential toxicity liabilities earlier, and thus proceed only with those
      molecules that have both efficacy at the target and a low potential for toxicity
      in the human population. In this review we will briefly describe the major ways
      in which transcriptome analysis is being applied in the pre-clinical safety
      assessment process, focusing primarily on four areas where transcriptome analysis
      has already begun to have impact. These include using transcriptome analysis to:
      1) understand mechanisms of toxicity: 2) predict toxicity: 3) develop in vivo and
      in vitro surrogate models and screens; and, 4) develop toxicity biomarkers. We
      will close by briefly addressing future trends and needs in the application of
      transcriptome analysis to drug safety assessment.

PMID- 15720271
TI  - Application of transcriptome analysis to clinical pharmacology studies.
AB  - Clinical pharmacology is the investigation of drug effects in humans. This review
      discusses the basic tenets of clinical pharmacology research, including
      pharmacokinetic and pharmacodynamic analysis, therapeutic window, and clinical
      trial design, and the issues that may arise in the application of transcriptome
      analysis to clinical pharmacology studies. Examples of how transcriptome analysis
      can be applied to clinical pharmacology research are described, including a model
      system of endotoxin challenge (in vitro and in vivo), and an example of a cross
      over drug study in normal volunteers. Various data display and analysis methods
      are also illustrated, including principal component analysis, hierarchical
      cluster analysis, and pathways analysis.

PMID- 15720273
TI  - Development of oncology drug response markers using transcription profiling.
AB  - Transcriptional profiling of a tumor's entire genomic complement has become a key
      tool in the analysis of human cancers and identification of novel markers to
      predict disease state, outcome, and response to therapy. At present, this
      technology provides the most comprehensive approach for the analysis of somatic
      changes altering critical pathways during transformation of stable diploid cells
      into unstable tumor cells. Such analyses are impacting the development of novel
      anti-cancer drugs through the early detection of cancer, development of targeted
      therapies, identification of optimal dose and regimens for new drugs, and
      segmentation of patients to enrich response rates and reduce risk of adverse
      events.

PMID- 15720272
TI  - Clinical pharmacogenomics and transcriptional profiling in early phase oncology
      clinical trials.
AB  - Microarray-based expression profiling studies in the field of oncology have
      demonstrated encouraging correlations between tumor transcriptional profiles and
      eventual patient outcomes. These findings have fueled great interest in the
      application of transcriptional profiling to samples available from real-time
      clinical trials, and clinical pharmacogenomic objectives utilizing
      transcriptional profiling strategies are becoming increasingly incorporated into
      clinical trial study designs. Over the last few years several retrospective
      studies based on the profiling of archival tumor tissues suggest that
      transcriptional analysis of oncology samples may provide general prognosis
      measures, and in some cases may even predict response to specific therapies.
      Recently the FDA released a voluntary genomic data guidance meant to assist both
      regulatory agencies and pharmaceutical companies alike in evaluating the
      potential benefit of implementing expression profiling studies during the
      preclinical and clinical phases of drug development. Despite the great promise
      afforded by this technology, the ultimate benefit of applying transcriptional
      profiling in prospective clinical trials has yet to be realized because a number
      of practical impediments to this process exist. The multi-fold purpose of the
      current review is to highlight the increasing evidence from studies that have
      identified transcriptional signatures in archived tumors prognostic of patient
      outcome, to describe some of the drivers for the implementation of
      transcriptional profiling strategies in real-time drug development, to discuss
      the use of transcriptional profiling in the context of increasingly complex
      translational medicine strategies, and to highlight the practical issues and
      potential approaches involved in the successful application of clinical
      pharmacogenomic objectives during real-time clinical trials. Strategic
      implementation of transcriptional profiling in early oncology clinical trials can
      provide an opportunity to identify predictive markers of clinical response and
      eventually provide a substantial step forward towards the era of personalized
      medicine.

PMID- 15720274
TI  - DNA microarrays in clinical cancer research.
AB  - The recent sequencing of the human genome, coupled with advances in
      biotechnology, is enabling the comprehensive molecular "profiling" of human
      tissues. In particular, DNA microarrays are powerful tools for obtaining global
      views of human tumor gene expression. Complex information from tumor "expression
      profiling" studies can, in turn, be used to create novel molecular cancer
      diagnostics. We discuss the utility of DNA microarray-based tumor profiling in
      clinical cancer research, highlight some important recent studies, and identify
      future avenues of research in this evolving field.

PMID- 15720275
TI  - The role of synovial fibroblasts in mediating joint destruction in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease with systemic
      involvement that affects about 1% of the Western population. The progressive
      destruction of affected joints is a major characteristic of the disease and
      distinguishes RA from other acute and chronic arthritides. The etiology of RA is
      unknown, and a variety of genetic and environmental factors are being discussed
      as potential causes of the disease. However, in contrast to our incomplete
      understanding of the etiology, the knowledge about molecular mechanisms leading
      to joint destruction has advanced considerably over the past years. Thus, a large
      number of studies have investigated the presence and interplay of several types
      of cells in rheumatoid synovium, such as lymphocytes, macrophages and
      fibroblasts. They have led to the understanding that cells in the rheumatoid
      synovium form a network, which interacts through direct cell-to cell contacts as
      well as the release of a multitude of cytokines. The use of novel molecular
      techniques together with the development of new animal models has revised our
      concept on the pathogenesis of RA and specifically on the role of fibroblasts in
      initiation and progression of joint destruction. This article will review current
      data and hypotheses on disease mechanisms by which fibroblasts are involved in
      the destruction of joints in RA.

PMID- 15720276
TI  - The role of macrophages in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common autoimmune chronic inflammatory joint
      disease, characterized by macrophage and lymphocyte infiltration, proliferation
      of synovial fibroblasts, and joint destruction. Macrophages are critically
      involved in the pathogenesis of RA. Not only do they produce a variety of pro
      inflammatory cytokines and chemokines, but they also contribute to the cartilage
      and bone destruction in RA through multiple mechanisms. Macrophage activation by
      several distinct mechanisms is crucial for their function. This review will
      discuss several aspects of macrophage function in RA, including the mechanisms
      for macrophage activation, the signaling pathways in activated macrophages, and
      the mechanisms that inhibit apoptosis in macrophages in the rheumatoid joints.

PMID- 15720277
TI  - Signal transduction pathways and transcription factors as therapeutic targets in
      inflammatory disease: towards innovative antirheumatic therapy.
AB  - Many chronic inflammatory diseases are associated with deregulated intracellular
      signal transduction pathways. Resultant pathogenic interactions between immune
      and stromal cells lead to changes in cell activation, proliferation, migratory
      capacity, and cell survival that all contribute to inflammation. Increasing
      efforts are now being made in the design of novel therapeutic compounds to
      interfere with signaling pathways in inflammatory diseases like rheumatoid
      arthritis (RA). In this review we will outline the major signal transduction
      pathways involved in the pathogenesis of RA. We will assess advances in targeting
      a number of key intracellular pathways, including nuclear factor-(kappa)B (NF
      (kappa)B), mitogen-associated protein kinases (MAPKs), phosphoinositide 3-kinase
      (PI3K)/Akt, signal transducers and activators of transcription (STATs), and
      reactive oxygen species (ROS) production. Finally, we will discuss recently
      identified lead molecules and the progress of selected compounds towards becoming
      new drugs for the treatment of inflammatory diseases.

PMID- 15720278
TI  - Chemokine expression and regulation of angiogenesis in rheumatoid arthritis.
AB  - Regulation of angiogenesis occurs in the context of particular microenvironments
      and is governed by a sensitive balance between angiogenic and anti-angiogenic
      mediators. Under normal physiologic conditions, the expansion of existing blood
      vessels is held in check suggesting that homeostasis is maintained by a
      predominance of angiostatic factors. In the rheumatoid arthritis joint, it is
      probable that the expansive and tumor-like synovial pannus that invades cartilage
      requires additional nutrients and oxygen. In the face of these demands, there is
      likely a shift in the balance such that angiogenic mediators predominate leading
      to neovascularization, a hallmark of rheumatoid arthritis. Chemokines are a
      subset of cytokines that primarily mediate physiologic and pathophysiologic
      leukocyte trafficking during inflammation and immune cell differentiation.
      Chemokines are also fundamental participants, along with a variety of other
      factors, which regulate angiogenesis. Within the CXC family of chemokines, there
      is functional discrepancy, where some family members are angiogenic and others
      are angiostatic. Moreover, the expression of several chemokines has been well
      documented in rheumatoid arthritis synovial tissues and fluids. This review will
      discuss what is known about the role of specific chemokines in the regulation of
      angiogenesis with particular emphasis on those chemokines likely to participate
      in rheumatoid arthritis.

PMID- 15720279
TI  - Soluble adhesion molecules in the pathogenesis of rheumatoid arthritis.
AB  - Rheumatoid arthritis is chronic systemic inflammatory disease that is
      characterized by joint swelling and leukocyte recruitment into synovial tissue.
      Within the peripheral blood and synovial fluid of patients with rheumatoid
      arthritis there are many soluble mediators that function together to create an
      inflammatory environment ultimately responsible for the synovial pannus formation
      and subsequent joint destruction. One such group of soluble mediators present in
      the peripheral blood and synovial fluid of rheumatoid arthritic patients are
      soluble adhesion molecules. Soluble adhesion molecules are commonly formed as the
      result of cell surface adhesion molecule shedding due to cell stimulation, but
      may also be the result of de novo synthesis of truncated soluble forms of
      adhesion molecules. There has been debate over the function of soluble adhesion
      molecules in the inflammatory process. Soluble adhesion molecules have been shown
      to both enhance and inhibit different aspects of the inflammatory process.
      However, the preponderance of research studying rheumatoid arthritis has shown
      soluble adhesion molecules to be important regulators of leukocyte recruitment
      into the synovial tissue. This review will focus on the soluble adhesion
      molecules that have been studied in peripheral blood and synovial fluids of
      patients with rheumatoid arthritis. The role of different soluble adhesion
      molecules in the pathogenesis of rheumatoid arthritis will be discussed, as will
      the effects of common disease modifying anti-rheumatic therapies on their
      production.

PMID- 15720280
TI  - A role for the complement system in rheumatoid arthritis.
AB  - The production of autoreactive antibodies from self-reactive B cells results in
      the formation of immune complexes that deposit in tissue and fix complement,
      contributing to the pathogenesis of rheumatoid arthritis (RA). Earlier mouse
      models emphasize the importance of autoreactive antibodies formed against "self"
      proteins that serve as a source for T cell-mediated immune response, stemming
      from cross-reactivity and resulting in B cell activity. However, more recent
      models suggest the need for both autoantibodies and the initiation of the
      inflammatory cascade via the alternative complement pathway, which is unbridled
      as the cartilage lacks the usual regulatory proteins of the complement system.
      Furthermore, deficiencies in specific complement proteins could lead to an escape
      from negative selection by these self-reactive B cells. Moreover, the classical
      complement pathway establishes chemotactic gradients by which inflammatory cells
      follow and accumulate in the synovial fluid where they engulf immune complexes
      and release proteolytic enzymes. In addition, the processing of circulating
      immune complexes either via Fc receptor or CR1 and opsonization by complement
      fragments plays a key role in determining the fate of immune status. In addition,
      complement proteins are a major determinant in the size and solubility of an
      immune complex, which also affects clearance. The evidence regarding intra
      articular activation of the complement system in RA provides the possibility to
      pharmacologically manipulate various parts of the complement system for
      therapeutic purposes and potential therapeutic targets for the control of
      inflammation and the prevention of joint destruction.

PMID- 15720281
TI  - Current and future pharmaceutical therapy for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, inflammatory arthritis with a population
      prevalence of approximately 1%. Pharmaceutical treatment includes both anti
      inflammatory medications and disease modifying drugs (DMARDs) that impact the
      course of the damage associated with this disease. Traditional DMARD therapy
      includes immunomodulatory agents such as methotrexate, used both alone and in
      combination. Recently available biologic response modifiers are very effective at
      reducing both the clinical symptoms of disease and the radiographic damage that
      accompanies them. This manuscript describes the clinical assessments used to
      measure response to therapy in RA and reviews the results seen with the various
      treatment strategies in this disease. In addition, the clinical and structural
      outcomes seen in trials of newly available and pending biologic therapies are
      reviewed, along with the specific toxicity issues associated with these agents.
      Clinical trial data is reviewed for the TNF antagonists, which have become the
      standard of care in RA patients with an inadequate response to methotrexate. RA
      has been clearly shown to be a destructive and disabling disease. The widespread
      use of newer agents, however, along with more aggressive use of existing
      therapies, appears to limit disease progression very effectively, and should lead
      to better long-term outcomes for these patients.

PMID- 15720283
TI  - Recent methodologies for the estimation of n-octanol/water partition coefficients
      and their use in the prediction of membrane transport properties of drugs.
AB  - The lipophilicity of drug molecules (represented as the logarithm of the n
      octanol/water partition coefficient) often strongly correlates with their
      pharmacological and toxic activities. It is therefore, not surprising that there
      is considerable interest in developing mathematical models capable to accurately
      predict their value for new drug candidates. In this review, current major
      approaches for estimating partition coefficients are described and some of their
      advantages and disadvantages are discussed. Recent uses of these partition
      coefficient algorithms in the development of membrane transport models are also
      discussed.

PMID- 15720284
TI  - Inhibitors of multidrug efflux transporters: their membrane and protein
      interactions.
AB  - Modulators and inhibitors of multidrug efflux transporters, like P-glycoprotein,
      are used to reduce or inhibit multidrug resistance, MDR, which leads to a failure
      of the chemotherapy of e.g. cancers, epilepsy, bacterial, parasitic, and fungal
      diseases. Binding and transport of first-, second-, and third-generation
      modulators and inhibitors of P-glycoprotein are discussed, taking into account
      the properties of the drug (H-bonding potential, dimensions, and pK(a) values) as
      well as the properties of the membrane.

PMID- 15720285
TI  - Inhibitors of p-glycoprotein--lead identification and optimisation.
AB  - The membrane bound drug efflux pump P-glycoprotein (P-gp) transports a wide
      variety of functionally and structurally diverse cytotoxic drugs out of tumour
      cells. Overexpression of P-glycoprotein is one of the predominant mechanisms
      responsible for development of multiple drug resistance in tumour therapy. Thus,
      inhibition of P-gp represents a promising approach for treatment of multidrug
      resistant tumours. This review highlights concepts for identification and
      optimization of new inhibitors of P-glycoprotein.

PMID- 15720286
TI  - Photoaffinity labeling of P-glycoprotein.
AB  - The aim of the present review is to summarize recent progress in identifying
      substrate binding domains of P-glycoprotein by photoaffinity labeling. Preferred
      substrate binding regions have been identified using a number of photoaffinity
      ligands, including anthracyclines, the quinazoline iodoarylazidoprazosine (IAAP),
      dihydropyridines, taxanes and propafenones. These studies allowed identification
      of protein regions, which are involved in ligand interaction.

PMID- 15720287
TI  - Multidrug transporters in lactic acid bacteria.
AB  - Gram-positive lactic acid bacteria possess several Multi-Drug Resistance systems
      (MDRs) that excrete out of the cell a wide variety of mainly cationic lipophilic
      cytotoxic compounds as well as many clinically relevant antibiotics. These MDRs
      are either proton/drug antiporters belonging to the major facilitator superfamily
      of secondary transporters or ATP-dependent primary transporters belonging to the
      ATP-binding cassette superfamily of transport proteins. Here we summarize the
      existing data on these MDRs and discuss recent observations that suggest the use
      of new strategies in the ongoing battle against drug-resistant microbial
      pathogens.

PMID- 15720288
TI  - Efflux transporters and their clinical relevance.
AB  - It is increasingly recognized that efflux transporters play an important role,
      not only in chemo protection e.g. multi-drug resistance, but also in the
      absorption, distribution, and elimination of drugs. The modulation of drug
      transporters through inhibition or induction can lead to significant drug-drug
      interactions by affecting intestinal absorption, renal secretion, and biliary
      excretion, thereby changing the systemic or target tissue exposure of the drug.
      Few clinically significant drug interactions that affect efficacy and safety are
      due to a single mechanism and there is considerable overlap of substrates,
      inhibitors, and inducers of efflux transporters and drug metabolizing enzymes,
      such as CYP3A. As well, genetic polymorphisms of efflux transporters have been
      correlated with human disease and variability of drug exposure. Accordingly, this
      review will discuss drug interactions and suitable probe substrates, as well as,
      the clinical relevance of the variability and modulation of efflux transporters
      and the exploitation of substrates as diagnostic tools. An update is given on
      inhibitors, which clinically reverse drug resistance and minimize the risk of
      metabolic interactions.

PMID- 15720289
TI  - The impact of lipophilicity in drug research: a case report on beta-blockers.
AB  - The key importance of lipophilicity in bio-studies is discussed for beta
      blockers. Examples of their lipophilicity-dependent pharmacological properties
      including pharmacokinetic, pharmacodynamic and clinical aspects are reviewed.
      Comprehensive lipophilicity compilations of beta-blockers are lacking so far.
      LogP calculations with 10 programs for 30 clinically relevant beta-blockers are
      presented for the first time in this review.

PMID- 15720290
TI  - Effect of okadaic acid on glucose regulation.
AB  - Okadaic acid is the main toxin responsible for the natural phenomena known as
      diarrheic shellfish poisoning (DSP). This toxin is a tumor promoter C38 polyether
      fatty acid that contains acidic and hydrophobic moieties and is cyclic. Okadaic
      acid is a potent inhibitor of important classes of protein serine/threonine
      phosphatases such as protein phosphatase 1 and 2A. The toxin binds in a
      hydrophobic groove adjacent to the active site of the protein phosphatases and
      interacts with basic residues within the active site. Therefore okadaic acid
      causes increases in phosphorylation of proteins that affect a diverse array of
      cellular processes. For instance, this toxin modulates metabolic parameters in
      intact cells. In this sense it stimulates lipolysis, and inhibits fatty acid
      synthesis in adipocytes however increases glucose output and gluconeogenesis in
      hepatocytes. Additionally, okadaic acid reaches cytotoxic concentrations in the
      intestinal tissues in accordance with the diarrhea. Recent studies suggested that
      toxic effects of okadaic acid might be related to modification of nutrients,
      ionic and water absorption across the small intestine presumably by altering the
      transporter system. The subject of this review is limited to the effect of
      okadaic acid on glucose regulation and its cellular as well as clinical
      implications.

PMID- 15720291
TI  - Focus on recent approaches for the development of new NO-donors.
AB  - Recent research developments in the field of NO-donor compounds have concerned
      conjugation of NO-donor moieties with antioxidant groups, NO-donor targeting,
      design of NO-donor hybrid drugs and of NO-delivery systems. These new approaches
      are illustrated and discussed through selected examples.

PMID- 15720292
TI  - Characterizing monoclonal antibody epitopes by filtered gene fragment phage
      display.
AB  - In the present paper, we describe a novel approach to map monoclonal antibody
      epitopes, using three new monoclonal antibodies that recognize h-TG2 (human
      transglutaminase 2) as an example. The target gene was fragmented and cloned
      upstream of an antibiotic-resistance gene, in the vector pPAO2, to select for in
      frame polypeptides. After removal of the antibiotic-resistance gene by Cre/Lox
      recombination, an antigen fragment phage display library was created and selected
      against specific monoclonal antibodies. Using the h-TG2 fragment library, we were
      able to identify epitopes. This technique can also be broadly applied to the
      study of protein-protein interactions.

PMID- 15720293
TI  - Interaction between the bacterial nucleoid associated proteins Hha and H-NS
      involves a conformational change of Hha.
AB  - The H-NS family of proteins has been shown to participate in the regulation of a
      large number of genes in Gram-negative bacteria in response to environmental
      factors. In recent years, it has become apparent that proteins of the Hha family
      are essential elements for H-NS-regulated gene expression. Hha has been shown to
      bind H-NS, although the details for this interaction are still unknown. In the
      present paper, we report fluorescence anisotropy and NMR studies of the
      interaction between Hha and H-NS64, a truncated form of H-NS containing only its
      N-terminal dimerization domain. We demonstrate the initial formation of a complex
      between one Hha and two H-NS64 monomers in 150 mM NaCl. This complex seems to act
      as a nucleation unit for higher-molecular-mass complexes. NMR studies suggest
      that Hha is in equilibrium between two different conformations, one of which is
      stabilized by binding to H-NS64. A similar exchange is also observed for Hha in
      the absence of H-NS when temperature is increased to 37 degrees C, suggesting a
      key role for intrinsic conformational changes of Hha in modulating its
      interaction with H-NS.

PMID- 15720294
TI  - More roles for selenoprotein P: local selenium storage and recycling protein in
      the brain.
AB  - How is the essential micronutrient, selenium (Se), transported in the serum and
      then donated to tissues? In this issue of the Biochemical Journal, Schweizer and
      colleagues demonstrate, using conditional and total mouse knockout models, that
      SePP (selenoprotein P) is the major transporter of Se in the serum. Moreover, in
      the sanctuary area of the brain, SePP was shown to play a hitherto unexpected
      role as a local Se storage and recycling protein that directly maintains brain Se
      levels. Considering the function of Se in normal brain metabolism, these results
      are crucial for our understanding of the role of selenoproteins in redox
      regulation, antioxidant defences, thyroid hormone metabolism and the development
      of neurodegenerative conditions.

PMID- 15720295
TI  - Analysis of Y-chromosome variability and its comparison with mtDNA variability
      reveals different demographic histories between islands in the Azores Archipelago
      (Portugal).
AB  - We determined the Y-chromosomal composition of the population of the Azores
      Islands (Portugal), by analyzing 20 binary polymorphisms located in the non
      recombining portion of the Y-chromosome (NRY), in 185 unrelated individuals from
      the three groups of islands forming the Archipelago (Eastern, Central and
      Western). Similar to that described for other Portuguese samples, the most
      frequent haplogroups were R1(xR1b3f) (55.1%), E(xE3a) (13%) and J (8.6%).
      Principal components analysis revealed a Western European profile for the Azorean
      population. No significant differences between Azores and mainland Portugal were
      observed. However, the haplogroup distribution across the three groups of islands
      was not similar (P<0.003). The Western group presented differences in the
      frequencies of haplogroups R1, E(xE3a) and I1b2 (27.3%, 22.7% and 13.6%,
      respectively) when compared to the other two groups. An assessment of the NRY
      variability, and its comparison with mitochondrial DNA (mtDNA) variability, was
      further evidence of the differential composition of males during the settlement
      of the three groups of islands, contrary to what has been previously deduced for
      the female settlers using mtDNA data.

PMID- 15720296
TI  - The Y-chromosomal heritage of the Azores Islands population.
AB  - The Azores, a Portuguese archipelago located in the north Atlantic Ocean, had no
      native population when the Portuguese first arrived in the 15th century. The
      islands were populated mainly by the Portuguese, but Jews, Moorish prisoners,
      African slaves, Flemish, French and Spaniards also contributed to the initial
      settlement. To understand the paternal origins and diversity of the extant
      Azorean population, we typed genomic DNA samples from 172 individuals using a
      combination of 10 Y-biallelic markers (YAP, SRY-1532, SRY-2627, 92R7, M9, sY81,
      Tat, SRY-8299, 12f2 and LLY22g) and the following Y-chromosomal STR systems:
      DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393 and DYS385. We identified nine
      different haplogroups, most of which are frequent in Europe. Haplogroup J* is the
      second most frequent in the Azores (13.4%), but it is modestly represented in
      mainland Portugal (6.8%). The other non-European haplogroups, N3 and E3a, which
      are prevalent in Asia and sub-Saharan Africa, respectively, have been found in
      the Azores (0.6% and 1.2%, respectively) but not in mainland Portugal.
      Microsatellite data indicate that the mean gene diversity (D) value for all the
      loci analysed in our sample set is 0.590, while haplotype diversity is 0.9994.
      Taken together, our analysis suggests that the current paternal pool of the
      Azorean population is, to a great extent, of Portuguese descent with significant
      contributions from people with other genetic backgrounds.

PMID- 15720297
TI  - Linkage analysis of plasma ApoE in three ethnic groups: multiple genes with
      context-dependent effects.
AB  - We performed variance component-based linkage analysis in four samples (two of
      non-Hispanic European-Americans from Rochester, MN; African-Americans from
      Jackson, MS; and Mexican-Americans from Starr County, TX) to identify chromosomal
      regions containing genes influencing plasma apolipoprotein E (apoE) levels. The
      APOE gene region on chromosome (chr) 19 was identified with a LOD > or = 2.00 in
      both samples from Rochester and the sample from Jackson. Adjustment of apoE
      levels for differences among means of genotypes defined by the APOE epsilon2/3/4
      alleles reduced evidence of linkage, indicating that the APOE gene was
      responsible for the majority of the linkage signal. In stratified linkage
      analyses, there was a LOD of 1.70 in the Starr County sibships with average total
      cholesterol (TC) above the median level for all sibships in that population.
      Adjustment for APOE genotype did not remove this LOD score, suggesting a second
      gene in this region may influence apoE variation. Evidence of linkage (LOD= 3.32)
      on chr 17 was observed in the Starr County sibships with average TC below the
      median. Inter-individual variation in plasma apoE level may be influenced by
      variations in the structural gene, and at least one other gene whose effects
      differ among populations and are dependent on the influence of unmeasured genetic
      and environmental factors indexed by correlated measures of lipid metabolism.

PMID- 15720298
TI  - Haplotype effects on human survival: logistic regression models applied to
      unphased genotype data.
AB  - Haplotype based linkage disequilibrium (LD) mapping exhibits higher power than
      the single locus approach because it makes use of the LD information contained in
      the flanking markers. New statistical methods have been proposed to help to infer
      haplotype effects on human diseases using multi-locus genotype data collected
      from unrelated individuals. In this paper, we introduce a statistical procedure
      for measuring haplotype effects on human survival using the popular logistic
      regression model with haplotype based parameterizations. By modeling haplotype
      frequency as a function of age, our model infers haplotype effects by estimating
      and testing the slope parameters under different genetic mechanisms
      (multiplicative, dominant, or recessive). In addition, by estimating the sex
      specific slope parameters, our model allows the detection of sex-specific
      haplotype effects or haplotype-sex interactions. As an example, we apply our
      model to an empirical dataset on a stress related gene, interleukin-6, to look
      for haplotypes that affect individual survival and for haplotype-sex
      interactions. We show that our logistic regression based haplotype model can be a
      helpful tool for researchers interested in the genetics of human aging and
      longevity.

PMID- 15720299
TI  - Generating genetic risk scores from intermediate phenotypes for use in
      association studies of clinically significant endpoints.
AB  - While previous results of genetic association studies for common, complex
      diseases (eg., coronary artery disease, CAD) have been disappointing, examination
      of multiple related genes within a physiologic pathway may provide improved
      resolution. This paper describes a method of calculating a genetic risk score
      (GRS) for a clinical endpoint by integrating data from many candidate genes and
      multiple intermediate phenotypes (IPs). First, the association of all single
      nucleotide polymorphisms (SNPs) to an IP is determined and regression beta
      coefficients are used to calculate an IP-specific GRS for each individual,
      repeating this analysis for every IP. Next, the IPs are assessed by a second
      regression as predictors of the clinical endpoint. Each IP's individual GRS is
      then weighted by the regression beta-coefficients from the second step, creating
      a single, composite GRS. As an example, 3,172 patients undergoing coronary
      angiography were evaluated for 3 SNPs from the cholesterol metabolism pathway.
      Although these data provide only a preliminary example, the GRS method detected
      significant differences in CAD by GRS group, whereas separate genotypes did not.
      These results illustrate the potential of the GRS methodology for multigenic risk
      evaluation and suggest that such approaches deserve further examination in
      common, complex diseases such as CAD.

PMID- 15720300
TI  - High resolution T association tests of complex diseases based on family data.
AB  - This paper proposes family based Hotelling's T(2) tests for high resolution
      linkage disequilibrium (LD) mapping or association studies of complex diseases.
      Assume that genotype data of multiple markers or haplotype blocks are available
      for a sample of nuclear families, in which some offspring are affected. Paired
      Hotelling's T(2) test statistics are proposed for a high resolution association
      study using parents as controls for affected offspring, based on two coding
      methods: haplotype/allele coding and genotype coding. The paired Hotelling's T(2)
      tests take not only the correlation between the haplotype blocks or markers into
      account, but also take the correlation within each parent-offspring pair into
      account. The method extends two sample Hotelling's T(2) test statistics for
      population case control association studies, which are not valid for family data
      due to correlation of genetic data among family members. The validity of the
      proposed method is justified by rigorous mathematical and statistical proof under
      the large sample theory. The non-centrality parameter approximations of the test
      statistics are calculated for power and sample size calculations. From power
      comparison and type I error calculations, it is shown that the test statistic
      based on haplotype/allele coding is advantageous over the test statistic of
      genotype coding. Analysis using multiple markers may provide higher power than
      single marker analysis. If only one marker is utilized the power of the test
      statistic based on haplotype/allele coding is nearly identical to that of 1-TDT.
      Moreover, a permutation procedure is provided for data analysis. The method is
      applied to data from a German asthma family study. The results based on the
      paired Hotelling's T(2) statistic tests confirm the previous findings. However,
      the paired Hotelling's T(2) tests produce much smaller P-values than those of the
      previous study. The permutation tests produce similar results to those of the
      previous study; moreover, additional marker combinations are shown to be
      significant by permutation tests. The proposed paired Hotelling's T(2) statistic
      tests are potentially powerful in mapping complex diseases. A SAS Macro,
      Hotel_fam.sas, has been written to implement the method for data analysis.

PMID- 15720301
TI  - The effect of SNP marker density on the efficacy of haplotype tagging SNPs--a
      warning.
AB  - We investigate here the efficacy of selecting haplotype tagging SNPs at different
      marker densities (2kb-10kb). Our results are based on publicly available data on
      5324 markers with a median spacing of 1kb from chromosome 20. We find that
      whatever density of SNPs is used, htSNP analysis indicates in most cases that at
      least 80% of the variation can be captured using a subset of SNPs. However, as
      marker density decreases these htSNPs become increasingly unreliable. In this
      dataset htSNPs were selected to capture at least 80% of the variation at every
      observed SNP. At an observed SNP density of 2kb, htSNP analysis suggests that the
      htSNPs capture on average 95% of the observed variation, when in fact they
      capture 88% of the unobserved variation. At a density of 10kb, htSNP analysis
      suggests that 93% of the observed variation was captured, when in fact they
      capture on average only 78%. Our results indicate that htSNP analysis is only
      reliable when markers are dense--a spacing of even 2kb shows a considerable loss
      of information. Such findings are important both for individual studies utilising
      htSNPs to reduce costs, and for projects such as HapMap which try to characterise
      human genomic variation using htSNPs.

PMID- 15720303
TI  - dHPLC screening of the NSD1 gene identifies nine novel mutations--summary of the
      first 100 Sotos syndrome mutations.
AB  - Sotos syndrome belongs to the family of overgrowth syndromes and is characterized
      by large head circumference, craniofacial anomalies, advanced bone age and mental
      retardation. The syndrome is due to haploinsufficiency of the NSD1 gene,
      consisting of 23 exons with an open reading frame of 8088bp, which makes mutation
      screening by direct sequencing quite a laborious and expensive task. We have
      developed a dHPLC screening protocol for mutation detection in NSD1 and
      identified 9 novel mutations among 33 patients, thus achieving a mutation
      detection efficiency comparable to direct sequencing. A real-time quantitative
      PCR approach identified two patients with NSD1 deletions. Our mutation screen is
      compared to other studies and all published mutations and polymorphisms are
      summarized.

PMID- 15720302
TI  - Spinal muscular atrophy carrier screening by multiplex polymerase chain reaction
      using dried blood spot on filter paper.
AB  - Spinal muscular atrophy (SMA) is a common, often fetal, autosomal recessively
      inherited disease leading to progressive muscle wasting and paralysis as a result
      of degeneration of anterior horn cells of the spinal cord. The SMA-determining
      gene, called the survival of motor neuron gene (SMN), is present on 5q13 in two
      nearly identical copies, telomeric SMN (SMN1) and centromeric SMN (SMN2). It has
      been established that SMA is caused by mutations in SMN1 whereas homozygous
      deletion of SMN2 has apparently no pathological consequences. The aim of this
      study is to develop an easy and inexpensive method for the isolation of high
      quality template DNA from blood samples for SMA carrier screening by multiplex
      polymerase chain reaction. We have developed a protocol that optimizes detection
      of the SMN1 copy number in the human genome, producing a specific and sensitive
      assay using DNA extracted from a dried blood spot on IsoCode paper.

PMID- 15720304
TI  - SNP haplotypes in the angiotensin I-converting enzyme (ACE) gene: analysis of
      Nigerian family data using gamete competition models.
AB  - Gamete competition models were used to explore the relationships between 13 ACE
      gene polymorphisms and plasma ACE concentration in a set of Nigerian families.
      Several markers in the 5' and 3' regions of the gene were significantly
      associated with ACE concentration (P < 10(-4)). Multi-locus genotypes comprising
      different combinations of markers from the 5' UTR and the 3' region of the gene
      were also analysed; in addition to G2350A, in the 3' region, two markers from the
      5' UTR (A-5466C and A-240T) were found to be associated with ACE concentration.
      These results are consistent with reports that have suggested the presence of at
      least two ACE-linked QTLs, and demonstrate the utility of gamete competition
      models in the exploratory investigation of the relationship between a
      quantitative trait and multiple variants in a small genomic region.

PMID- 15720305
TI  - A method for pooling alleles from different genotyping experiments.
AB  - Single tandem repeat (STR) polymorphisms are widely used in linkage and
      association studies. One of the drawbacks of using these markers is that genetic
      data coming from different experiments cannot be easily pooled together, because
      both allele length and binning distance may change. As large studies with
      multiple series of subjects sequentially included become more and more common,
      there is an increasing interest in pooling the genetic data obtained in different
      experiments. Correct reconstruction of allelic correspondences between genotyping
      experiments is particularly crucial for association-oriented studies, such as
      candidate gene studies and genome-wide association studies in isolated
      populations. Here, we suggest a maximum-likelihood framework to find the best
      correspondence between alleles typed in different genotyping experiments. We also
      address the issue of goodness-of-fit and robustness. We perform a study
      simulating results obtained in a genome scan using 787 STR markers. The
      simulations show that the suggested method yields good results with respect to
      the error rate, even if the sizes of the samples to be pooled are as low as 10
      subjects (3% errors), though only 9% of alleles pass our tests. As sample sizes
      increase to 250 subjects the proportion of alleles pooled reaches 96% with an
      error rate of <0.1%.

PMID- 15720306
TI  - Health infrastructure in very remote areas: an analysis of the CRANA Bush Crisis
      Line database.

PMID- 15720307
TI  - Preparedness for rural community leadership and its impact on practice location
      of family medicine graduates.
AB  - OBJECTIVE: To identify non-clinical dimensions of preparedness for rural practice
      and to determine whether preparedness for rural practice is predictive of rural
      practice location. DESIGN: Cross-sectional postal survey mailed in 2001. SETTING:
      Communities across Canada where graduates were practising. SUBJECTS: Graduates (n
      = 369) of the family medicine residency program at the universities of Alberta (U
      of A) and Calgary (U of C) between 1996 and 2000, inclusive. INTERVENTIONS: Using
      a 4-point scale, graduates rated the extent to which the residency program
      prepared them for eight dimensions of rural practice: clinical demands of rural
      practice, understanding rural culture, small community living, balancing work and
      personal life, establishing personal/professional boundaries, becoming a
      community leader, handling a 'fish bowl' lifestyle, and choosing a suitable
      community. MAIN OUTCOME MEASURE: Identification of non-clinical dimensions of
      preparedness for rural practice and whether scores on preparedness scales are
      predictive of rural practice location. RESULTS: The overall response rate was
      76.4%. Factor analysis of the eight preparedness items produced two factors,
      'rural culture' and 'rural community leader' which explained 72% of the variance.
      The alpha coefficient for each factor was 0.87. Odds ratios revealed that family
      medicine graduates prepared for rural community leadership roles were 1.92 (CI =
      1.03-3.61) times more likely to be in rural practice. Rural physicians were also
      2.14 (CI = 1.13-4.03) times as likely to have a rural background. CONCLUSIONS:
      Preparedness to be a rural community leader and having a rural background were
      predictive of rural practice. Educators should consider this in both family
      medicine residency admissions policy and practice and when designing and
      implementing family medicine residency curricula.

PMID- 15720308
TI  - Developing everyone's capacity: a resource kit supporting workforce capacity in
      reducing falls risk in the older person.

PMID- 15720309
TI  - Support needs of supply nurses in rural and remote Queensland.
AB  - OBJECTIVE: The aim of this report is to discuss a needs analysis conducted with
      rural and remote nurses in Queensland undertaking supply of medications in public
      hospitals without a pharmacist. DESIGN: Survey questionnaire. METHODS: A
      questionnaire was faxed to 65 Queensland Health rural and remote hospitals using
      supply nurses. It contained six closed questions regarding previously identified
      medication 'supply' issues, and three open questions to determine additional
      information. RESULTS: Of the surveys, 42 (65%) were returned. Major areas of
      interest included a safety checklist for medication supply (90%, 38/42), more
      information on medication labelling requirements (83%, 35/42) and timing of
      medications with regard to food (86%, 36/42). Requirements for patient
      counselling, increased access to consumer medication information (CMI) (76%,
      32/42), and resources regarding doses, indications, interactions and adverse
      effects also rated highly (73%, 31/42). Thirty-three supply nurses highlighted at
      least one issue in the open questions: more information on the legal requirements
      of repackaging medications (39%, 13/42), increased access to CMI and counselling
      tools (36%, 12/42) and an efficient stock control system (30%, 10/42).
      CONCLUSIONS: This report highlights the need to broaden current support services
      available to nurses undertaking the supply of medications. It is vital that
      support programs, and the laws and guidelines related to supplying medications in
      rural and remote hospitals, support health care professionals providing quality
      use of medicines (QUM) and reflect the realities of rural and remote health care.

PMID- 15720310
TI  - Doctors in vocational training: rural background and rural practice intentions.
AB  - OBJECTIVE: To report the findings of a national survey of Australian doctors in
      vocational training about their rural practice intentions and their plans to work
      full time or part time. DESIGN: A self-administered mailed survey. SETTING:
      Vocational training: general practice and other medical college training
      programs. SUBJECTS: Australian doctors (i.e. Australian citizens and permanent
      residents) registered with one of Australia's 17 medical college vocational
      training programs in September 2002. MAIN OUTCOME MEASURES: Intention to practise
      in a rural area on completion of vocational training; full-time or part-time
      practice plans; views about rural practice. RESULTS: Of the 7899 doctors who met
      the criteria for inclusion in the study, 4259 (54%) responded. In total:14%
      indicated a preference for rural practice on completion of vocational training;
      17% were GP trainees of which 31% preferred rural practice; 83% were registered
      with one of the other 16 specialist training programs (e.g. adult medicine,
      paediatric medicine and surgery) of which 10% preferred rural practice; 50% of
      general practice trainees and 23% of trainees in other specialist training
      programs with a rural background indicated a preference for rural practice in the
      long term, compared with 25% and 7%, respectively, of doctors with an urban
      background; 46% of general practice trainees with intentions to practise in a
      rural area plan to practise part time. A positive association was observed
      between rural background and preference for rural practice (odds ratio (OR) 2.9)
      and between preference for rural practice and enrollment in the rural general
      practice training pathway (OR 3.1) and involvement in rural education and
      training activities (OR 5.1). CONCLUSIONS: The findings of this study support
      initiatives to increase the number of rural background students entering medical
      school and rural education and vocational training initiatives. Australia's rural
      doctor shortage is not likely to be addressed by this cohort of doctors in
      vocational training. General practice workforce plans, rural and urban, need to
      take note of the high proportion of doctors who plan to practise part time.

PMID- 15720311
TI  - Caring for depressed patients in rural communities: general practitioners'
      attitudes, needs and relationships with mental health services.
AB  - OBJECTIVE: To examine the needs and practices of rural GPs and their
      relationships with local acute mental health services, particularly in the
      provision of care to depressed patients. DESIGN: Postal survey. SETTING: Rural
      general practices. SUBJECTS: Ninety-nine GPs (63 males, 36 females) from the
      Hunter Valley region of NSW, Australia. MAIN OUTCOME MEASURES: GPs' self-reported
      contact rates, confidence, needs and beliefs. RESULTS: Depression was the most
      commonly seen mental disorder, with an average of 1.44 patients per GP per month
      referred to local acute mental health services, most commonly for suicidality.
      The preferred form of feedback after the referral of a depressed patient was a
      follow-up letter, while the most requested type of patient management support was
      cognitive behavioural therapy (CBT) groups. GPs were most confident in
      recognising depression, compared to other mental disorders except anxiety, and
      they were most confident in treating depression, compared to all other mental
      disorders. The most common barrier to providing care for depressed patients was
      reported to be 'time constraints' on GPs. CONCLUSIONS: The challenge for mental
      health services is to develop ways to collaborate more effectively with GPs in
      the provision of psychological services for depressed patients in rural
      communities.

PMID- 15720312
TI  - Faecal incontinence: an unrecognised epidemic in rural North Queensland? Results
      of a hospital-based outpatient study.
AB  - OBJECTIVES: We explored the prevalence of faecal incontinence (FI) in a referral
      hospital outpatient population, to explore suspicions that FI is inadequately
      studied, underestimated and poorly appreciated in the rural North Queensland (NQ)
      community. DESIGN: Prospective cross-sectional study using a specifically
      designed questionnaire. SETTING: The Townsville Hospital, a referral centre
      serving rural NQ. SUBJECTS: A total of 435 consecutive patients attending the
      gynaecology (n = 261) and colorectal clinics (n = 174) between 31 January and 12
      June 2003 were enrolled (participating proportion 96.5%). MAIN OUTCOME MEASURES:
      FI prevalence, severity, impact on patients' lives, and risk factors. RESULTS:
      The prevalence of FI in the study population (median age 53 years) was 20.7%.
      Amongst affected patients (n = 90) the median duration of FI was 2 years with
      more than half of those affected soiling themselves at least once a month. Many
      patients with FI (42%) reported feeling hopeless at least some of the time.
      Rectal prolapse, chronic constipation, psychiatric problems, colon disease, and
      urinary incontinence were all significantly associated with FI. A CART analysis
      revealed that many patients (45%) with urinary incontinence and chronic
      constipation also experienced FI. CONCLUSIONS: This FI prevalence in a clinical
      setting in NQ is, apart from nursing home studies, the highest reported in the
      literature. FI negatively impacted on affected persons' lives. In patients
      presenting with urinary incontinence and chronic constipation, physicians should
      specifically enquire whether FI is also present. Definitive community studies to
      determine the scale of this 'silent epidemic' in northern Australia are now
      required.

PMID- 15720313
TI  - Masculine interest behind high prevalence of female contraceptive methods in
      rural Nepal.
AB  - OBJECTIVE: This article explores the nexus between intraspousal power relations
      and couples' participation in contraceptive decision-making. Further, it
      discloses whether perceived gender roles and privilege influence couples'
      contraceptive behaviour in rural Nepal. METHODS: Two hundred and twenty-three
      couples from 197 randomly selected households from two rural population clusters
      in eastern Nepal were interviewed. Additionally, 40 key informants were included
      to collect in-depth qualitative information. The conclusion provides the essence
      of the results from quantitative and qualitative analyses. RESULTS: Out of 10
      independent variables regarding the social power status of the wives and husbands
      (education, age, occupation, personal income, household headship, political
      participation, social participation, access to mass media, exposure to
      psychological assault and physical assault from husband), four variables, namely
      education, personal income, exposure to psychological assault and physical
      assault demonstrated significant influence on wives' participation, while no one
      variable showed association with husbands' participation in contraceptive
      decision-making. Despite the husband's domination, husband-wife joint involvement
      in making contraceptive decisions was common. However, stereotyped gender roles
      and privilege appeared to be influential in deciding the types of methods to use,
      to shift the methods, and to terminate using contraception. CONCLUSION: As an
      unequal conjugal relationship is one of the factors responsible for the husband's
      domination in the decision-making process, women's empowerment should be an entry
      point for the transformation of gender discriminatory attitudes and behaviour.
      Women's empowerment enhances an equal conjugal relationship, and thereby helps in
      achieving equal partnership in reproductive health decision-making.

PMID- 15720315
TI  - A report on perception of smoking prevention for children among schoolteachers in
      one Japanese rural community.

PMID- 15720314
TI  - Do rural consumers expect a prescription from their GP visit? Investigation of
      patients' expectations for a prescription and doctors' prescribing decisions in
      rural Australia.
AB  - OBJECTIVE: To assess patients' expectation for receiving a prescription and GPs'
      perceptions of patient expectation for a prescription. DESIGN: Matched
      questionnaire study completed by patients and GPs. SETTING: Seven general
      practices in rural Queensland, Australia. SUBJECTS: The subjects were 481
      patients consulting 17 GPs. MAIN OUTCOME MEASURES: Patients' expectation for
      receiving a prescription and GPs' perceptions of patients' expectation. RESULTS:
      Ideal expectation (hope) for a prescription was expressed by 57% (274/481) of
      patients. Sixty-six per cent (313/481) thought it was likely that the doctor
      would actually give them a prescription. Doctors accurately predicted hope or
      lack of hope for a prescription in 65% (314/481) of consultations, but were
      inaccurate in 19% (93/481). A prescription was written in 55% of consultations.
      No increase in patients' expectation, doctors' perceptions of expectation, or
      decision to prescribe were detected for patients living a greater distance from
      the doctors. CONCLUSIONS: Rural patients demonstrated similar rates of hope for a
      prescription to those found in previous urban studies. Rural doctors seem to be
      similarly 'accurate' and 'inaccurate' in determining patients' expectations.
      Rates of prescribing were comparable to urban rates. Distance was not found to
      increase the level of patient expectation, affect the doctors' perception or to
      influence the decision to prescribe.

PMID- 15720318
TI  - Landscape of fulfilment: for discussion.

PMID- 15720319
TI  - Choices and 'could have beens'.

PMID- 15720320
TI  - The fax as an effective telehealth tool.

PMID- 15720321
TI  - Redefining rural and remote physiotherapy practice.

PMID- 15720325
TI  - SARRAH: in a nutshell.

PMID- 15720326
TI  - ACRRM: The power behind vertical integration.

PMID- 15720327
TI  - Proceedings of the First World Summit on Kidney Surgery. February 5-7, 2003.
      Cleveland, Ohio, USA.

PMID- 15720328
TI  - The genetic basis of cancer of kidney cancer: implications for gene-specific
      clinical management.

PMID- 15720329
TI  - Nomograms for renal cell carcinoma.

PMID- 15720330
TI  - Role of three-dimensional imaging in surgical planning for kidney surgery.

PMID- 15720331
TI  - Laparoscopic radical nephrectomy: current status.

PMID- 15720332
TI  - Laparoscopic radical nephrectomy: specimen extraction.

PMID- 15720333
TI  - Open partial nephrectomy for renal tumours: current status.

PMID- 15720334
TI  - Laparoscopic partial nephrectomy for tumour: current status at the Cleveland
      Clinic.

PMID- 15720336
TI  - Open live donor nephrectomy: current status.

PMID- 15720335
TI  - Extracorporeal ablation of renal tumours with high-intensity focused ultrasound.

PMID- 15720337
TI  - Handling the distal ureter during open nephroureterectomy: principles and
      techniques.

PMID- 15720338
TI  - Radical laparoscopic nephroureterectomy for upper urinary tract transitional cell
      carcinoma: current status.

PMID- 15720339
TI  - Surgical revascularization for renal artery disease: current status.

PMID- 15720340
TI  - Percutaneous renal access: tips and tricks.

PMID- 15720341
TI  - Management of ureteric stones: issues and controversies.

PMID- 15720342
TI  - Ureteroscopic endoureterotomy.
AB  - OBJECTIVE: To highlight the current status of ureteroscopic endoureterotomy (UE)
      by reporting extensive experience with the endoscopic management of ureteric
      strictures, with special emphasis on factors determining success, and by
      reviewing publications on the minimally invasive management of ureteric
      strictures. PATIENTS AND METHODS: The study comprised 50 patients (mean age 53
      years, range 18-85, equal sex distribution) with ureteric strictures of varying
      causes; all had their stricture treated endoscopically. The follow-up was 0.5-9
      years; 10 patients with recurrent strictures had two ipsilateral stents placed to
      try to improve the outcome, and eight patients with completely obliterating
      strictures were treated by ureteroscopic re-canalization. RESULTS: The site of
      stricture had no bearing on the eventual outcome. Patients with uretero-enteric
      and malignant strictures did not fare so well. The most important predictor of
      failure was the length of the stricture, with failure in all seven patients with
      strictures of > 2 cm. In the 10 patients treated with two ipsilateral stents,
      eight were successful, which was very promising considering that these patients
      had recalcitrant strictures and placing one stent had previously failed. The
      overall success rate was 74%. CONCLUSION: UE has become the procedure of choice
      for the initial management of ureteric strictures. Simple balloon dilatation is
      also effective in certain situations. The characteristics of the stricture often
      govern the eventual outcome. In properly selected cases success rates of
      approximately 75% can be expected.

PMID- 15720344
TI  - Percutaneous endopyeloplasty: current clinical status.

PMID- 15720343
TI  - Laparoscopic pyeloplasty: current status.
AB  - OBJECTIVE: To review current publications and report our results and long-term
      follow-up of laparoscopic transperitoneal pyeloplasty for pelvi-ureteric junction
      (PUJ) obstruction. PATIENTS AND METHODS: In all, 147 laparoscopic transperitoneal
      pyeloplasties were performed between August 1993 and November 2000 (mean patient
      age 35.7 years, range 10-85). All patients were diagnosed with PUJ obstruction by
      symptoms and intravenous urography, radionuclide diuretic renography or
      ultrasonography. An Anderson-Hynes dismembered pyeloplasty (106), Y-V plasty
      (28), Fenger plasty (11) and others (two) were used, according to the
      intraoperative findings. Twenty-five patients had secondary obstruction, having
      had previous surgery to the PUJ. The mean (range) follow-up was 24 (3-84) months;
      all patients were followed clinically and radiologically. RESULTS: The mean
      operative duration time was 246 (100-480) min and estimated blood loss was 158
      mL. Crossing vessels were identified in 80 cases. The success rate for all,
      primary and secondary patients was 95%, 98% and 84%, respectively. With one
      exception, all failures occurred within 6 months. Twenty-one patients (22 renal
      units) had simultaneous laparoscopic pyeloplasty and lithotomy; they were treated
      successfully and all have an intact PUJ, and 20 renal units (90%) were stone
      free. The overall complication rate was 8.8%. CONCLUSIONS: This series has
      comparable success rates to those of open pyeloplasty and the morbidity was
      minimal. Laparoscopic pyeloplasty may soon become the standard operation for PUJ
      obstruction, especially with crossing vessels.

PMID- 15720345
TI  - Advanced renal laparoscopy.

PMID- 15720347
TI  - Systematic review of thromboprophylaxis in colorectal surgery -- an update.
AB  - OBJECTIVE: The incidence of thromboembolism after colorectal surgery is higher
      than after general surgery. The aim of this paper is to update a systematic
      review addressing thrombosis prophylaxis in connection with colorectal surgery.
      METHODS: MEDLINE, EMBASE, LILACS, abstract books and reference lists from reviews
      were searched without language restrictions for randomized controlled trials or
      clinical controlled trials comparing prophylactic interventions and/or placebo up
      til August 2003. Five hundred and fifty-eight studies were identified of which 19
      fulfilled the inclusion criteria. Data extraction was done by at least two of the
      authors. Outcome was deep venous thrombosis and/or pulmonary embolism diagnosed
      by various methods. RESULTS: Any kind of heparin is better than no treatment or
      placebo (11 studies) with a Peto Odds ratio (POR) at 0.32 (95% CI 0.20-0.53).
      Unfractionated heparin and low molecular weight heparin (4 studies) were equally
      effective POR 1.01 (95% CI 0.67-1.52). The combination of graduated compression
      stockings and LMWH is better than LMWH alone (2 studies) with a POR at 4.17 (95%
      CI 1.37-12.70). CONCLUSION: The optimal thromboprophylaxis in colorectal surgery
      is the combination of graduated compression stockings and low-dose unfractionated
      heparin or low molecular weight heparin.

PMID- 15720348
TI  - Diet and colorectal cancer: implications for the obese and devotees of the Atkins
      diet.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer-related death
      in the Western world and its prevalence is increasing. Potential causes of this
      increase are changes in diet and the increases in obesity seen. This paper looks
      at the literature surrounding diet and obesity and the links to this increase in
      CRC. Heralded as a weight loss miracle we investigate whether the literature
      suggests the Atkins diet may actually do more harm than good by acting to
      increase an individual's risk of CRC. Obesity has been demonstrated to be a major
      factor in the increase in CRC although links to changes in diet are more tenuous.
      Published studies on diet suggest the Atkins diet may help reduce rather than
      increase the risk of CRC.

PMID- 15720349
TI  - Postoperative morbidity and recurrence after local excision of rectal adenomas
      and rectal cancer by transanal endoscopic microsurgery.
AB  - OBJECTIVE: Tumours in the middle and upper part of the rectum are not easy
      accessible to local excision. Transanal endoscopic microsurgery (TEM) has been
      recommended for excision of sessile adenomas in the middle and upper part of the
      rectum, and for small cancers in patients not fit for major surgery. The purpose
      of this study was to evaluate postoperative morbidity and local recurrence after
      TEM. MATERIAL AND METHODS: Seventy-nine patients were treated by TEM in the
      period 1994-2001. The median age was 74 years. The indications for TEM were
      rectal adenoma in 72 patients and rectal cancer in 7 patients. The tumours were
      located within 18 cm from the dentate line, median 10 cm. There were performed 69
      transmural and 10 mucosal excisions. Mean follow up was 24 months (range 1-95
      months). Twenty (25%) patients died during the follow up period, two because of
      metastases and 18 of other causes. RESULTS: Seven patients had complications. Two
      (2.5%) patients had peroperative perforation in the intra-abdominal part of the
      rectum treated by laparotomy. Five (6%) patients had postoperative cardiopulmonal
      or surgical complications. Eight patients with benign pre-operative
      histopathological examination had cancer. The local recurrence rate (13%) was
      similar for adenomas and for carcinomas. CONCLUSION: TEM is a safe technique well
      tolerated also by high-risk patients, and should be the preferred method in
      patients with benign tumours in the middle and upper part of the rectum, and in
      selected cases of early rectal cancer. Benign pre-operative histology does not
      preclude malignancy and some patients may need further treatment for unexpected
      malignancy.

PMID- 15720350
TI  - Bipolar electrocoagulation vs conventional monopolar hot biopsy forceps in the
      endoscopic treatment of diminutive rectal adenomas.
AB  - OBJECTIVE: To assess whether a cold biopsy from a diminutive rectal adenoma
      followed by destruction with bipolar (gold probe) electrocoagulation using large
      probes and high power setting would be a safe and efficient alternative to
      conventional monopolar hot biopsy forceps (MHBF). PATIENTS AND METHODS: Eligible
      patients were those undergoing colonoscopy, fulfilling the criteria of additional
      clearing colonoscopy and having at least one suspected rectal adenoma < or = 5
      mm. At the time of endoscopy patients were randomized to receive treatment for
      their diminutive rectal adenomas either with cold biopsy followed by repeated
      gold probe electrocoagulation (Group A) using a 10 Fr catheter with setting 8 (40
      W) for 1 second or with MHBF (Group B). These patients were followed up with a
      colonoscopy at 2-4 months. RESULTS: A total number of 24 (15 males, 9 females;
      mean age 56 years) patients were included in group A and 26 (14 males, 12
      females; mean age 58 years) in group B. A total number of 38 and 37 diminutive
      rectal adenomas was detected in patients of Group A and Group B, respectively. At
      follow up colonoscopy residual adenoma tissue was found in 2 (5.2%) adenomas of
      38 in Group A and in 4 (10.8%) of 37 in Group B (P > 0.3). No complications
      related to colonoscopy or endoscopic treatments in both groups occurred.
      CONCLUSIONS: Our data suggest that the use of cold biopsy followed by bipolar
      electrocoagulation using large probes and high power setting for destroying
      diminutive rectal adenoma seems to be equally effective and safe as MHBF.

PMID- 15720351
TI  - An approach to haemorrhoids.
AB  - OBJECTIVE: Many patients with haemorrhoids are investigated because of the fear
      of missing colorectal cancer (CRC). The aim of this study was to determine
      whether a primarily clinical approach regarding the need for investigation was
      safe and did not miss patients with CRC. PATIENTS AND METHODS: Data was collected
      prospectively on 589 consecutive patients with the principle diagnosis of
      haemorrhoids at first clinic visit. All had clinical assessment including rigid
      sigmoidoscopy and were treated by phenol injection or banding. They were
      categorized for (1) no review unless symptoms persisted -'One Stop SOS' (2)
      outpatient review or (3) investigation. To check for the development of CRC they
      were contacted by postal questionnaire or telephone interview with a minimum of
      one year from diagnosis and treatment. All 589 patients were cross-referenced
      with the Pathology database and the Hospital Information Services System.
      RESULTS: Four hundred and sixty-nine (80%) answered the questionnaire; 352
      patients (60% of the total group) fell in the 'one stop SOS' outpatient category;
      95 (16%) patients were followed up to review response to treatment for large
      haemorrhoids; 105 (18%) were investigated with barium enema (12%), flexible
      sigmoidoscopy (4%), colonoscopy (1%) and miscellaneous (1%); 37 (6%) patients
      were either given a haemorrhoidectomy date or referred on with a different
      diagnosis. No patients selected for 'one-stop' treatment developed CRC. Five
      (0.8%) patients were diagnosed with CRC after appropriate investigation was
      instituted for suspicious symptoms. One patient with distal transverse colon
      cancer had a delayed diagnosis as she was investigated initially by flexible
      sigmoidoscopy. CONCLUSION: Most patients with the primary diagnosis of
      symptomatic haemorrhoids do not need investigation.

PMID- 15720352
TI  - The role of colonoscopic endoanal ultrasound scanning (EUS) in selecting patients
      suitable for resection by transanal endoscopic microsurgery (TEM).
AB  - OBJECTIVE: This study was performed to assess the accuracy of colonoscopic
      endoanal ultrasound scanning (EUS) in the selection of patients with rectal
      neoplasia suitable for local excision by transanal endoscopic microsurgery (TEM).
      Our policy is to offer TEM to patients with premalignant (T0) lesions or with T1
      tumours that have early disease. PATIENTS AND METHODS: Data were collected
      prospectively on all patients undergoing EUS for the assessment of rectal
      neoplasia at our institution over a six-year period. A colonoscopic EUS probe was
      used to determine whether the tumour breached the muscularis propria (the
      interface between T1 and T2 disease). Subsequently patients underwent surgical
      resection, including TEM for those with T0/1 disease. The preoperative stage
      predicted by EUS (uT stage) was compared to the postoperative histopathological
      stage of the resected specimens (pT stage). RESULTS: One hundred and fifty-six
      EUS examinations were evaluated. Sixty-two patients went on to have TEM whilst
      the remaining 94 had another form of surgery. Of the 62 patients undergoing TEM,
      3 were overstaged on EUS. No patients were understaged, giving an accuracy of
      95%. Of the 94 patients undergoing an alternative procedure, 5 were overstaged on
      EUS as having T2 tumours when in fact their histology was T1. Accuracy of EUS at
      predicting more advanced disease fell to 89%, giving an overall accuracy of 92%.
      CONCLUSIONS: EUS is accurate at predicting T0/1 vs T2 disease in our institution,
      and we believe that it is a useful modality in assessing patient suitability for
      local excision.

PMID- 15720353
TI  - Long-term outcome of laparoscopic mesh rectopexy for solitary rectal ulcer
      syndrome.
AB  - OBJECTIVE: To determine the long-term outcome of laparoscopic mesh rectopexy for
      solitary rectal ulcer syndrome (SRUS). PATIENTS AND METHODS: A retrospective
      review of 11 patients who underwent laparoscopic mesh rectopexy for refractory
      SRUS between 1993 and 1996. All patients were followed up initially with rigid
      sigmoidoscopy and seven were involved in long-term evaluation (follow-up at 71
      106 months, median 89 months) involving a sickness impact profile questionnaire.
      RESULTS: Complete endoscopic healing of the ulcer was demonstrated in all 11
      patients up to one year postoperatively but one suffered recurrence later. Of
      seven assessed long-term, none experienced endoscopic recurrence. Six continued
      to enjoy a significant reduction in symptoms and an improved quality of life. One
      had persistent problems and demonstrated little symptomatic improvement.
      CONCLUSION: Laparoscopic mesh rectopexy offers a minimally invasive option for
      selected patients who remain severely symptomatic despite maximal conservative
      therapy for SRUS, with demonstrable ulcer healing and long-term improvement in
      symptoms and quality of life. Larger studies are required to fully evaluate its
      efficacy compared to 'conventional' surgical options.

PMID- 15720354
TI  - Laparoscopic or trephine faecal diversion: is there a preferred approach and why?
AB  - BACKGROUND: Faecal diversion is often indicated in perineal sepsis and in the
      palliation of advanced ano-rectal malignancy. This can be performed open or
      laparoscopically. The aim of this study was to assess the outcome of these two
      approaches to stoma creation. METHODS: Prospective evaluation of laparoscopic or
      'trephine' stoma creation in 49 consecutive unselected patients. RESULTS:
      Eighteen (37%) patients (median age 68 years) underwent a laparoscopic approach
      in which there were no conversions. One patient required a laparotomy for stoma
      mal-orientation and there were two (11%) deaths. Thirty-one patients (median age
      70 years) had a trephine stoma formed with two (6%) conversions but no deaths.
      Thirteen (42%) of these patients had surgery performed under regional
      anaesthesia. There was no difference in the hospital stay between the two groups
      and at a mean follow-up of 16 months, 20 (41%) patients had died mainly from
      disease progression. CONCLUSION: Both approaches to faecal diversion give
      adequate results in the short term. Laparoscopic techniques should be reserved
      for fitter patients as a trephine stoma can be performed under regional
      anaesthesia.

PMID- 15720355
TI  - The role of rectocele repair in targeted patients with obstructed defaecation.
AB  - INTRODUCTION: Obstructed defaecation is a complex disorder that poses serious
      management challenges. The purpose of this study is to review the functional
      results of surgery in women undergoing rectocele repair for obstructed
      defaecation, and in a targeted subgroup in which the rectocele was the only
      identifiable cause of their symptoms. METHODS: All case notes were reviewed.
      Demographic details, preoperative symptoms, details of previous pelvic surgery,
      radiological and anorectal physiology results, operative procedure, post
      operative symptoms, length of follow-up and details of further pelvic
      reconstructive surgery were recorded. To enter the targeted group, patients (i)
      had not undergone previous pelvic surgery, (ii) had presented with obstructive
      defaecation, (iii) had a proctogram that demonstrated a rectocele with no or
      partial intrarectal intussusception and (iv) had no other functional abnormality
      in colonic transit studies, endoanal ultrasound or anorectal physiology. RESULTS:
      Eighty-two case notes were reviewed. All experienced obstructed defaecation.
      Forty-two women underwent a per-anal plication of the rectocele, 33 had a
      transperineal plication and levatorplasty and seven a mesh repair. A total of 63
      (77%) women were pleased with the result, though symptoms later returned in 17
      (27%) of them. 26 (31%) had further surgery in an attempt to improve their
      defaecatory difficulties. Sixteen women were eligible for the targeted group. All
      had a good early result though symptoms returned in three women. Two (12%) had
      further surgery. CONCLUSION: Careful preoperative patient selection is vital to
      improve outcomes. Preoperative counselling of all patients undergoing rectocele
      repair is of extreme importance, in particular explaining the evolving nature of
      pelvic floor dysfunction and the possible need for further reconstructive
      surgery.

PMID- 15720356
TI  - Infliximab in the surgical management of complex fistulating anal Crohn's
      disease.
AB  - OBJECTIVES: To assess prospectively the efficacy and safety of treatment of
      perianal Crohn's disease by means of a combination of surgical management and a
      standardized protocol for the intravenous infusion of infliximab. METHODS: A
      consecutive series of patients who presented with complex perianal Crohn's
      fistulae between November 1999 and March 2003 were included in the study.
      Perianal sepsis was eradicated with drainage of collections and insertion of
      setons. Infliximab was infused at 5 mg/kg at 0, 2, and 6 weeks. Setons were
      removed after the second infliximab infusion. Endpoints were defined as either
      complete, partial or no response as noted at subsequent outpatient follow up.
      Adverse reactions were recorded. RESULTS: Twenty-one patients had a median of
      three fistulae per patient (range 1-9). All patients tolerated the initial
      protocol, receiving a median of five infusions of infliximab (range 3-19); median
      follow up 20 months (range 12-52). Eleven patients (53%) were continued on
      maintenance therapy with 12 weekly infusions of infliximab for either a perceived
      clinical need for treatment or after a relapse of their symptoms. Ten (47%)
      patients experienced a complete response to treatment and the remaining 11 (53%)
      experienced a partial response. No patient failed to respond to treatment. Four
      adverse reactions were noted (2 mild allergies, 1 rash and 1 patient experienced
      joint pains). All adverse reactions settled with cessation of the drug infusion.
      CONCLUSIONS: The combination of seton drainage and infusion of infliximab
      completely healed the perineum of 47% patients with complex fistulating perianal
      Crohn's disease. Partial response was seen in the remainder of patients. No
      serious adverse reactions reported.

PMID- 15720357
TI  - Targets and elective colorectal cancer: outcome and symptom delay at surgical
      resection.
AB  - OBJECTIVE: To determine, for elective patients with colorectal cancer, if
      associations exist between the length of symptom history at surgical resection
      and Dukes stage, completeness of the surgical procedure and patient survival.
      PATIENTS AND METHODS: A prospective cohort study was undertaken. Five hundred and
      eighty-two patients with colorectal cancer, admitted for surgical resection after
      outpatient consultation, divided into four equal quartiles according to length of
      symptom history (short: n = 131, 0-103 days; medium: n = 136, 104-177 days; long:
      n = 136, 178-318 days; very long: n = 137, 319-1997 days). The main outcome
      measures used were the Extent of tumour (Dukes stage) at resection, completeness
      of resectional surgery (curative vs palliative), patient survival after
      resection. RESULTS: For patients undergoing elective surgical resection of
      colorectal cancer we did not find an association between Dukes stage and duration
      of patient history (Dukes stage C tumours were seen in 37% (CI: 26.2%-48.0%) of
      patients with a short symptomatic history as opposed to 34% (CI: 32%-62%) with a
      very long symptomatic history). Elective curative resection was not associated
      with a significantly different symptom duration than elective palliative
      resection (Palliative resections were performed in 24% (CI: 11.7%-36.4%) of
      patients with a short symptomatic history as opposed to 16% (CI: 2.4%-29.9%) with
      a very long symptomatic history). The median survival time for the four elective
      colorectal patient groups defined by length of symptomatic history was not
      significantly different - (short: n = 131, 4.3 years; medium: n = 136, 5.9 years;
      long: n = 136, 7.1 years; very long: n = 137, 5.0 years). CONCLUSION: Tumour
      extent, completeness of resection and patient outcome after elective colorectal
      cancer resection was not found to have an association with length of patient
      history at the time of surgery.

PMID- 15720358
TI  - Pathological audit of stapled haemorhoidopexy.
AB  - INTRODUCTION: Stapled haemorrhoidopexy is increasingly used for the surgical
      management of prolapsing haemorrhoids. Accurate placement of the staple line is
      essential to avoid involvement of the internal anal sphincter (IAS) and the pain
      sensitive squamous epithelium. The aim of this study was to correlate histology
      with symptomatic outcome after stapled haemorrhoidopexy. PATIENTS AND METHODS: A
      single pathologist reviewed one hundred and six consecutive rectal mucosal
      specimens. Each specimen was assessed for the presence of columnar, transitional
      and squamous epithelium as well as involvement of smooth and skeletal muscle. In
      November 2003 all patients were sent a previously validated postal questionnaire
      about haemorrhoidal symptoms and a Cleveland Clinic continence scale. Symptomatic
      outcome was compared between patients who did or did not have squamous epithelium
      involvement in their pathology specimens and were analysed by Mann-Whitney U
      test. RESULTS: One hundred and six stapled haemorrhoidopexies were performed
      between June 2001 and September 2003. Eighty-four patients (79%) returned the
      questionnaire; 19 patients had squamous epithelium present in the pathology
      specimens. There was no significant difference between symptom or Cleveland
      Clinic scores in patients with or without squamous epithelium in their pathology
      specimens. Some specimens (n = 6) were found to have smooth muscle underlying
      squamous epithelium; this was interpreted as the presence of internal anal
      sphincter (IAS) within the specimen. There was no significant difference in
      Cleveland Clinic scores between this group and those without IAS involvement.
      CONCLUSION: This study has not demonstrated a long-term difference in symptomatic
      outcome or continence in patients who have squamous epithelium present in their
      stapled haemorrhoidopexy specimens.

PMID- 15720359
TI  - What factors influence survival in patients with unresected synchronous liver
      metastases after resection of colorectal cancer?
AB  - OBJECTIVE: The aim of this study was to determine whether the survival of
      patients with untreated synchronous liver metastases after resection of a
      colorectal cancer was associated with any features of the primary tumour.
      METHODS: Information for 398 consecutive patients with unresected liver
      metastases in the period 1971-2001 was examined by multivariate survival
      analysis. RESULTS: Of 19 clinical and pathological variables considered, survival
      was independently associated only with residual tumour in a line of resection
      (hazard ratio (HR) 1.95), venous invasion (HR 1.87), right colonic tumour (HR
      1.68), lymph node metastasis (HR 1.54), and extra-hepatic metastasis (HR 1.16);
      8.3% of patients had none of these adverse features. Their 2-year overall
      survival rate was 39.2%, compared with only 16.5% (P < 0.001) in those with one
      or more adverse features. CONCLUSIONS: These findings may assist in selecting
      patients most likely to benefit from treatment of hepatic metastases and in
      counselling patients and their relatives.

PMID- 15720360
TI  - Rifaximin-ciprofloxacin combination therapy is effective in chronic active
      refractory pouchitis.
AB  - OBJECTIVE: Treatment of chronic refractory pouchitis is often difficult and
      disappointing and some of the affected pouches subsequently fail. This study was
      conducted to evaluate the efficacy and tolerability of treatment with rifaximin,
      a nonabsorbable oral antibiotic with immunomdulatory functions, in combination
      with ciprofloxacin for chronic active refractory pouchitis. PATIENTS AND METHODS:
      Eight patients with chronic active refractory pouchitis were treated orally with
      a combination of rifaximin 1 g b.d and ciprofloxacin 500 mg b.d. for two weeks.
      Clinical assessment, endoscopic and histological evaluations were performed
      before and after therapy using the Pouchitis Disease Activity Index (PDAI) score.
      Improvement was defined as a decrease of at least three points in the PDAI score
      and remission as a PDAI score of 0. The Wilcoxon signed rank test was used to
      compare pre- and post-treatment PDAI scores. The long-term outcome of the treated
      patients was prospectively monitored. RESULTS: Seven of the eight patients either
      went into remission (n = 5) or improved (n = 2). The median (range) PDAI scores
      before and after therapy were 12 (9-18) and 0 (0-15), respectively, (P = 0.018).
      All patients were compliant and no side effects were reported. Pouchitis recurred
      in two of the seven responding patients but returned into remission after further
      courses of the same combination. After a median follow-up of 30 months, the seven
      responding patients still had satisfactory pouch function. CONCLUSION: Rifaximin
      ciprofloxacin combination therapy is safe and objectively effective in chronic
      active refractory pouchitis and may salvage a significant percentage of 'at risk
      pouches'.

PMID- 15720361
TI  - Ano-cutaneous flap repair for complex and recurrent supra-sphincteric anal
      fistula.
AB  - BACKGROUND: Suprasphincteric fistulae remain the most difficult to cure.
      OBJECTIVES: The purpose of this study was to evaluate the healing rate of
      suprasphincteric anal fistula treated by ano-cutaneous advancement flap repair,
      and the impact of this procedure on continence and quality of life. METHOD:
      Sixteen patients with complex, recurrent or chronic suprasphincteric fistulae
      associated with significant tissue damage (necrotizing fasciitis, keyhole
      deformity and anal stenosis) or who had failed previous surgical procedures were
      treated by ano-cutaneous flap closure. They were assessed pre and postoperatively
      by the treating surgeon for wound healing and fistula recurrence and later
      followed up by phone interview using the St Mark's Hospital incontinence score
      and the Perianal Disease Activity Index (PDAI) as indicators of treatment
      outcome. RESULTS: Fifteen patients had successful healing of their fistula with
      the cutaneous flap, with recurrence in only one. The most common short-term
      complications were minor graft site wound separation, which healed in all cases
      without intervention, and wound pain, which settled over time and was not
      associated with recurrence. Continence improved for almost 70% of the patients,
      with a significant reduction in St Mark's incontinence scores (t = 2.62, 15 d.f.,
      P = 0.02). PDAI also decreased significantly (t = 7.55, 15 d.f., P < 0.001),
      demonstrating improvement in quality of life for most patients. CONCLUSION: Ano
      cutaneous flap can achieve healing of complex and recurrent suprasphincteric anal
      fistula in patients who had previously failed at other forms of treatment thus
      improving their quality of life and continence.

PMID- 15720362
TI  - Thirty-day mortality from colorectal cancer surgery within a deprived population.
AB  - OBJECTIVE: A recently published model for predicting 30-day mortality has been
      devised using data from 73 hospitals in the UK. Deprivation category was not one
      of the data sets used in predicting mortality and was not included in formulating
      this model. We wished to assess if the model was applicable to a population with
      high deprivation category scores. METHODS: Data on all colorectal cancer
      operations included in the model (age, ASA, cancer resected, Dukes stage and
      urgency) had been collected prospectively since January 1999. This data was
      applied to the model. RESULTS: Two hundred and thirty patients were included in
      analysis. Overall predicted mortality was 8.2% and actual mortality 7.8%. Within
      different categories of deprivation, predicted and actual mortality are similar
      and not significantly different. 137 patients lived in areas of deprivation
      category 3-5. Predicted and actual mortality were 8.4% and 8.0%, respectively. In
      areas of deprivation category 6-7, 91 patients had a predicted and actual
      mortality of 8.0% and 7.7%. CONCLUSION: Although deprivation data was not
      included in the production of the mathematical model to predict postoperative
      death, the model appears to predict well in the deprived population. It is likely
      that poorer socio-economic status is accounted for by increased ASA and cancer
      stage.

PMID- 15720363
TI  - Diagnostic lessons learnt from a series of enterovesical fistulae.

PMID- 15720364
TI  - Temporary stoma after elective anterior resection of the rectum: an unsolved
      debate.

PMID- 15720367
TI  - The neuroscience of ADHD: multidisciplinary perspectives on a complex
      developmental disorder.

PMID- 15720368
TI  - Whither causal models in the neuroscience of ADHD?
AB  - In this paper we examine the current status of the science of ADHD from a
      theoretical point of view. While the field has reached the point at which a
      number of causal models have been proposed, it remains some distance away from
      demonstrating the viability of such models empirically. We identify a number of
      existing barriers and make proposals as to the best way for these to be overcome
      in future studies. These include the need to work across multiple levels of
      analysis in multidisciplinary teams; the need to recognize the existence of, and
      then model, causal heterogeneity; the need to integrate environmental and social
      processes into models of genetic and neurobiological influence; and the need to
      model developmental processes in a dynamic fashion. Such a model of science,
      although difficult to achieve, has the potential to provide the sort of framework
      for programmatic model-based research required if the power and sophistication of
      new neuroscience technologies are to be effectively exploited.

PMID- 15720369
TI  - Characterizing the ADHD phenotype for genetic studies.
AB  - The genetic study of ADHD has made considerable progress. Further developments in
      the field will be reliant in part on identifying the most appropriate phenotypes
      for genetic analysis. The use of both categorical and dimensional measures of
      symptoms related to ADHD has been productive. The use of multiple reporters is a
      valuable feature of the characterization of psychopathology in children. It is
      argued that the use of aggregated measures to characterize the ADHD phenotype,
      particularly to establish its pervasiveness, is desirable. The recognition of the
      multiple comorbidities of ADHD can help to isolate more specific genetic
      influences. In relation to both reading disability and conduct disorder there is
      evidence that genes may be involved in the comorbid condition that are different
      from pure ADHD. To date, progress with the investigation of endophenotypes for
      ADHD has been disappointing. It is suggested that extending such studies beyond
      cognitive underpinnings to include physiological and metabolic markers might
      facilitate progress.

PMID- 15720370
TI  - The control of responsiveness in ADHD by catecholamines: evidence for
      dopaminergic, noradrenergic and interactive roles.
AB  - We explore the neurobiological bases of attention deficit hyperactivity disorder
      (ADHD) from the viewpoint of the neurochemistry and psychopharmacology of the
      catecholamine-based behavioural systems. The contributions of dopamine (DA) and
      noradrenaline (NA) neurotransmission to the motor and cognitive symptoms of ADHD
      (e.g. hyperactivity, variable and impulsive responses) are studied in rodent and
      primate models. These models represent elements of the behavioural units observed
      in subjects with ADHD clinically, or in laboratory settings (e.g. locomotion,
      changed sensitivity/responsivity to novelty/reinforcement and measures of
      executive processing). In particular, the models selected emphasize traits that
      are strongly influenced by mesocorticolimbic DA in the spontaneously hypertensive
      (SHR) and the Naples high excitability (NHE) rat lines. In this context, the mode
      of action of methylphenidate treatment is discussed. We also describe current
      views on the altered control by mesolimbic catecholamines of appropriate and
      inappropriate goal-directed behaviour, and the tolerance or intolerance of
      delayed reinforcement in ADHD children and animal models. Recent insights into
      the previously underestimated role of the NA system in the control of
      mesocortical DA function, and the frontal role in processing information are
      elaborated.

PMID- 15720371
TI  - Towards an understanding of unique and shared pathways in the
      psychopathophysiology of ADHD.
AB  - Most attention deficit hyperactivity disorder (ADHD) research has compared cases
      with unaffected controls. This has led to many associations, but uncertainties
      about their specificity to ADHD in contrast with other disorders. We present a
      selective review of research, comparing ADHD with other disorders in
      neuropsychological, neurobiological and genetic correlates. So far, a specific
      pathophysiological pathway has not been identified. ADHD is probably not
      specifically associated with executive function deficits. It is possible, but not
      yet established, that ADHD symptoms may be more specifically associated with
      motivational abnormalities, motor organization and time perception. Recent
      findings indicating common genetic liabilities of ADHD and other conditions raise
      questions about diagnostic boundaries. In future research, the delineation of the
      pathophysiological mechanisms of ADHD needs to match cognitive, imaging and
      genetic techniques to the challenge of defining more homogenous clinical groups;
      multi-site collaborative projects are needed.

PMID- 15720372
TI  - Varieties of preschool hyperactivity: multiple pathways from risk to disorder.
AB  - In this paper we examine the characteristics of preschool attention deficit
      hyperactivity disorder (ADHD) from both mental disorder and developmental
      psychopathology points of view. The equivalence of preschool and school-aged
      hyperactivity as a behavioral dimension is highlighted together with the
      potential value of extending the use of the ADHD diagnostic category to the
      preschool period where these behaviours take an extreme and impairing form
      (assuming age appropriate diagnostic items and thresholds can be developed). At
      the same time, the importance of identifying pathways between risk and later ADHD
      is emphasized. Developmental discontinuity and heterogeneity are identified as
      major characteristics of these pathways. We argue that models that distinguish
      among different developmental types of early-emerging problems are needed. An
      illustrative taxonomy of four developmental pathways implicating preschool
      hyperactivity is presented to provide a framework for future research.

PMID- 15720373
TI  - Object identification in preschool children and adults.
AB  - We introduce computer-based methodologies for investigating object identification
      in 3- to 5-year-old children. In two experiments, preschool children and adults
      indicated when they could identify degraded pictures of common objects as those
      pictures either gradually improved or degraded in clarity. Clarity
      transformations were implemented in four ways: blurring, decreasing the picture's
      physical size, decreasing the pixel signal-to-noise ratio, and cropping. In
      Experiment 1, all age groups correctly identified objects at a more degraded
      state when those objects began moderately, as opposed to very, degraded and then
      clarified. This finding supports the notion that previous perceptual hypotheses
      interfere with object identification (i.e. the perceptual interference effect).
      In Experiment 2, children, but not adults, overestimated their ability to
      recognize objects in a degraded state when the object's identity was given to
      them beforehand. This suggests that for young children knowledge of the object's
      true identity cannot be ignored when evaluating their current perceptions. This
      is the first demonstration of the perceptual interference effect in children. We
      discuss both methodological and theoretical implications of the findings for
      research on object perception and theory of mind.

PMID- 15720374
TI  - Brain potentials to native and non-native speech contrasts in 7- and 11-month-old
      American infants.
AB  - Abstract Behavioral data establish a dramatic change in infants' phonetic
      perception between 6 and 12 months of age. Foreign-language phonetic
      discrimination significantly declines with increasing age. Using a longitudinal
      design, we examined the electrophysiological responses of 7- and 11-month-old
      American infants to native and non-native consonant contrasts. Analyses of the
      event-related potentials (ERP) of the group data at 7 and at 11 months of age
      demonstrated that infants' discriminatory ERP responses to the non-native
      contrast are present at 7 months of age but disappear by 11 months of age,
      consistent with the behavioral data reported in the literature. However, when the
      same infants were divided into subgroups based on individual ERP components, we
      found evidence that the infant brain remains sensitive to the non-native contrast
      at 11 months of age, showing differences in either the P150-250 or the N250-550
      time window, depending upon the subgroup. Moreover, we observed an increase in
      infants' responsiveness to native language consonant contrasts over time. We
      describe distinct neural patterns in two groups of infants and suggest that their
      developmental differences may have an impact on language development.

PMID- 15720375
TI  - Infants' enumeration of actions: numerical discrimination and its signature
      limits.
AB  - Are abstract representations of number - representations that are independent of
      the particular type of entities that are enumerated - a product of human language
      or culture, or do they trace back to human infancy? To address this question,
      four experiments investigated whether human infants discriminate between
      sequences of actions (jumps of a puppet) on the basis of numerosity. At 6 months,
      infants successfully discriminated four- versus eight-jump sequences, when the
      continuous variables of sequence duration, jump duration, jump rate, jump
      interval and duration, and extent of motion were controlled, and rhythm was
      eliminated. In contrast, infants failed to discriminate two- versus four-jump
      sequences, suggesting that infants fail to form cardinal number representations
      of small numbers of actions. Infants also failed to discriminate between
      sequences of four versus six jumps at 6 months, and succeeded at 9 months,
      suggesting that infants' number representations are imprecise and increase in
      precision with age. All of these findings agree with those of studies using
      visual-spatial arrays and auditory sequences, providing evidence that a single,
      abstract system of number representation is present and functional in infancy.

PMID- 15720376
TI  - They call it like they see it: spontaneous naming and attention to shape.
AB  - Two experiments explore children's spontaneous labeling of novel objects as a
      method to study early lexical access. The experiments also provide new evidence
      on children's attention to object shape when labeling objects. In Experiment 1,
      the spontaneous productions of 21 23- to 28-month-olds (mean 26;28) shown a set
      of novel, unnamed objects were analyzed both in terms of the specific words said
      and, via adult judgments, their likely perceptual basis. We found that children's
      spontaneous names were cued by the perceptual feature of shape. Experiment 2
      examines the relation between spontaneous productions, name generalizations in a
      structured task, and vocabulary development in a group of children between 17 and
      24 months of age (mean 21;6). Results indicate that object shape plays an
      important role in both spontaneous productions and novel noun generalization, but
      contrary to current hypotheses, children may name objects by shape from the
      earliest points of productive vocabulary development and this tendency may not be
      lexically specific.

PMID- 15720377
TI  - The robustness of learning through overhearing.
AB  - Two studies examined the robustness of vocabulary learning through overhearing by
      testing 48 2-year-olds in contexts in which a potentially distracting activity
      was present (Studies 1 and 2) and in which the novel word was embedded in a
      directive rather than a labeling statement (Study 2). The children were equally
      good at learning a novel object label when there was no distracting activity as
      when there was. They were also able to learn the word when the object was not
      explicitly labeled. These findings suggest that young children are keen observers
      of third-party interactions and that their linguistic input consists of more than
      just speech directly addressed to them.

PMID- 15720378
TI  - Aid in the midst of plenty: oil wealth, misery and advocacy in Angola.
AB  - This paper examines advocacy initiatives by humanitarian and human rights
      organisations to address problems of governance in resource-rich and conflict
      affected countries, focussing on the case of Angola. Humanitarian principles
      preclude the use of indiscriminate conditionality and point towards a cautious
      approach to advocacy aimed at assisting vulnerable populations. Furthermore, the
      relatively insignificant amount of aid supplied to resource-rich local
      authorities means that individual agencies have precious little leverage,
      especially when commercial interests rather than humanitarian or 'good
      governance' principles influence the priorities of bilateral donors. A context of
      resource wealth calls for: high levels of coordination and cooperation between
      human rights groups, aid agencies and donors; balanced use of conditionality,
      based on the drawing, by donors, of a clear distinction between emergency and
      development-oriented assistance; and a sustained effort to highlight the
      responsibilities of local authorities, foreign governments and businesses in
      meeting humanitarian and development objectives.

PMID- 15720379
TI  - Anatomy of an ambush: security risks facing international humanitarian
      assistance.
AB  - The 2003 war with Iraq has generated security concerns that present unique
      challenges to the practice of providing international humanitarian assistance
      during war and conflict. Objective research studies on security management are
      lacking. However, case studies have proven to be an important education and
      training tool to advance situational awareness of security risks. These
      challenges are illustrated by an analysis of the events surrounding the first
      ambush of, and assassination attempt on, a senior US aid official in Baghdad.
      Before deployment to conflict areas, especially those characterised by insurgent
      activity, humanitarian providers must realistically assess the threats to life
      and to the mission. They must obtain pre-deployment situational awareness
      education, security training and optimal protective equipment and vehicles.

PMID- 15720380
TI  - Civil society development versus the peace dividend: international aid in the
      Wanni.
AB  - Donors that provide aid to the Wanni region of Sri Lanka, which is controlled by
      the Liberation Tigers of Tamil Eelam (LTTE), are promoting initiatives that seek
      to advance the national peace process. Under the rubric of post-conflict
      reconstruction, the actions of political forces and structural factors have led
      to the prioritisation of two different approaches to peace-building: community
      capacity-building projects; and support for the 'peace dividend'. Both of these
      approaches face challenges. Cooperation with civil society actors is extremely
      difficult due to intimidation by the LTTE political authority and the
      authoritarian nature of its control. Peace-building successes with respect to the
      peace dividend are difficult to measure, and must be balanced against the
      negative effects of misdirected funds. Aid organisations must be careful not to
      consider the tasks of peacebuilding, humanitarian relief and community
      empowerment as either interchangeable or as mutually reinforcing endeavours.

PMID- 15720381
TI  - First-aid training and capabilities of the lay public: a potential alternative
      source of emergency medical assistance following a natural disaster.
AB  - Basic first-aid skills can be useful in treating minor injuries that commonly
      result from natural disasters in the United States. Yet there has been
      insufficient research on training and competence in first-aid skills among
      community residents. This study utilises panel data for 414 adults in Los
      Angeles, California, who were interviewed within three years of the 1994
      Northridge earthquake and re-interviewed in 1999 after the El Nino winter of 1997
      98. Descriptive, bivariate and multivariate analyses were performed. Results
      showed that 24 percent of the members of the sample had received first-aid
      training since their Northridge earthquake interview. First-aid training,
      particularly recent training, was associated with greater perceived first-aid
      skills, as well as with increased expected and actual employment of those skills.
      With the appropriate training and skill retention, lay members of the public can
      potentially contribute to a post-disaster medical response.

PMID- 15720382
TI  - An analysis of the causes and circumstances of flood disaster deaths.
AB  - The objective of this paper is to investigate and to improve understanding of the
      causes and circumstances of flood disaster deaths. A standardised method of
      classifying flood deaths is proposed and the difficulties associated with
      comparing and assessing existing information on flood deaths are discussed.
      Thirteen flood cases from Europe and the United States, resulting in 247 flood
      disaster fatalities, were analysed and taken as indicative of flood disaster
      deaths. Approximately two-thirds of the deaths occurred through drowning. Thus, a
      substantial number of flood disaster fatalities are not related to drowning.
      Furthermore, males are highly vulnerable to dying in floods and unnecessary risk
      taking behaviour contributes significantly to flood disaster deaths. Based on
      these results, recommendations are made to prevent loss of life in floods. To
      provide a more solid basis for the formulation of prevention strategies, better
      systematic recording of flood fatalities is suggested, especially those caused by
      different types of floods in all countries.

PMID- 15720383
TI  - Calcium--a universal carrier of biological signals. Delivered on 3 July 2003 at
      the Special FEBS Meeting in Brussels.
AB  - Calcium is the most universal carrier of signals to cells. Chosen by evolution
      because of its peculiar flexibility as a ligand, it now regulates all important
      aspects of cell activity, beginning with the creation of new life at
      fertilization and ending with the dramatic event of apoptotic suicide at the end
      of the life cycle. The process of signal transduction by Ca2+ displays a number
      of properties that make it unique among all other carriers of signals: for
      instance, the ability to perform both a first messenger and a second messenger
      function, or the frequent activation of autoregulatory mechanisms. The aspect
      that distinguishes the Ca2+ signaling function most dramatically is ambivalence.
      Cells have an absolute dependence on the messenger function of Ca2+ in order to
      function properly and must control its homeostasis with precision to maintain its
      free concentration in their interior at the appropriate low level. Catastrophy,
      however, invariably follows whenever protracted failures of the control
      mechanisms lead to sustained Ca2+ overload.

PMID- 15720384
TI  - Identification of versican as an isolectin B4-binding glycoprotein from mammalian
      spinal cord tissue.
AB  - Nociceptors are specialized nerve fibers that transmit noxious pain stimuli to
      the dorsal horn of the spinal cord. A subset of nociceptors, the nonpeptidergic C
      fibers, is characterized by its reactivity for the plant isolectin B4 (IB4) from
      Griffonia simplicifolia. The molecular nature of the IB4-reactive glycoconjugate,
      although used as a neuroanatomical marker for more than a decade, has remained
      unknown. We here present data which strongly suggest that a splice variant of the
      extracellular matrix proteoglycan versican is the IB4-reactive glycoconjugate
      associated with these nociceptors. We isolated (by subcellular fractionation and
      IB4 affinity chromatography) a glycoconjugate from porcine spinal cord tissue
      that migrated in SDS/PAGE as a single distinct protein band at an apparent
      molecular mass of > 250 kDa. By using MALDI-TOF/TOF MS, we identified this
      glycoconjugate unambiguously as a V2-like variant of versican. Moreover, we
      demonstrate that the IB4-reactive glycoconjugate and the versican variant can be
      co-released from spinal cord membranes by hyaluronidase, and that the IB4
      reactive glycoconjugate and the versican variant can be co-precipitated by an
      anti-versican immunoglobulin and perfectly co-migrate in SDS/PAGE. Our findings
      shed new light on the role of the extracellular matrix, which is thought to be
      involved in plastic changes underlying pain-related phenomena such as
      hyperalgesia and allodynia.

PMID- 15720385
TI  - Fluorescence quenching and kinetic studies of conformational changes induced by
      DNA and cAMP binding to cAMP receptor protein from Escherichia coli.
AB  - Cyclic AMP receptor protein (CRP) regulates the expression of more then 100 genes
      in Escherichia coli. It is known that the allosteric activation of CRP by cAMP
      involves a long-distance signal transmission from the N-terminal cAMP-binding
      domain to the C-terminal domain of CRP responsible for the interactions with
      specific sequences of DNA. In this report we have used a CRP mutant containing a
      single Trp13 located in the N-terminal domain of the protein. We applied the
      iodide and acrylamide fluorescence quenching method in order to study how
      different DNA sequences and cAMP binding induce the conformational changes in the
      CRP molecule. The results presented provide evidence for the occurrence of a long
      distance conformational signal transduction within the protein from the C
      terminal DNA-binding domain to the N-terminal domain of CRP. This conformational
      signal transmission depends on the promoter sequence. We also used the stopped
      flow and Forster resonance energy transfer between labeled Cys178 of CRP and
      fluorescently labeled DNA sequences to study the kinetics of DNA-CRP
      interactions. The results thus obtained lead to the conclusion that CRP can exist
      in several conformational states and that their distribution is affected by
      binding of both the cAMP and of specific DNA sequences.

PMID- 15720386
TI  - N-methyl-L-amino acid dehydrogenase from Pseudomonas putida. A novel member of an
      unusual NAD(P)-dependent oxidoreductase superfamily.
AB  - We found N-methyl-L-amino acid dehydrogenase activity in various bacterial
      strains, such as Pseudomonas putida and Bacillus alvei, and cloned the gene from
      P. putida ATCC12633 into Escherichia coli. The enzyme purified to homogeneity
      from recombinant E. coli catalyzed the NADPH-dependent formation of N-alkyl-L
      amino acids from the corresponding alpha-oxo acids (e.g. pyruvate,
      phenylpyruvate, and hydroxypyruvate) and alkylamines (e.g. methylamine,
      ethylamine, and propylamine). Ammonia was inert as a substrate, and the enzyme
      was clearly distinct from conventional NAD(P)-dependent amino acid
      dehydrogenases, such as alanine dehydrogenase (EC 1.4.1.1). NADPH was more than
      300 times more efficient than NADH as a hydrogen donor in the enzymatic reductive
      amination. Primary structure analysis revealed that the enzyme belongs to a new
      NAD(P)-dependent oxidoreductase superfamily, the members of which show no
      sequence homology to conventional NAD(P)-dependent amino acid dehydrogenases and
      opine dehydrogenases.

PMID- 15720387
TI  - Antioxidant defences in cybrids harboring mtDNA mutations associated with Leber's
      hereditary optic neuropathy.
AB  - Oxidative stress and imbalance between free radical generation and detoxification
      may play a pivotal role in the pathogenesis of Leber's hereditary optic
      neuropathy (LHON). Mitochondria, carrying the homoplasmic 11778/ND4, 3460/ND1 and
      14484/ND6 mtDNA point mutations associated with LHON, were used to generate
      osteosarcoma-derived cybrids. Enhanced mitochondrial production of reactive
      oxygen species has recently been demonstrated in these cybrids [Beretta S,
      Mattavelli L, Sala G, Tremolizzo L, Schapira AHV, Martinuzzi A, Carelli V &
      Ferrarese C (2004) Brain 127, 2183-2192]. The aim of this study was to
      characterize the antioxidant defences of these LHON-affected cells. The
      activities of glutathione peroxidase (GPx), glutathione reductase (GR),
      superoxide dismutases (SOD) and catalase, and the amounts of glutathione (GSH)
      and oxidized glutathione (GSSG) were measured in cybrids cultured both in glucose
      rich medium and galactose-rich medium. The latter is known to cause oxidative
      stress and to trigger apoptotic death in these cells. In spite of reduced SOD
      activities in all LHON cybrids, and of low GPx and GR activities in cells with
      the most severe 3460/ND1 and 11778/ND4 mutations, GSH and GSSG content were not
      significantly modified in LHON cybrids cultured in glucose medium. In contrast,
      in galactose, GSSG concentrations increased significantly in all cells,
      indicating severe oxidative stress, whereas GR and MnSOD activities further
      decreased in all LHON cybrids. These data suggest that, in cells carrying LHON
      mutations, there is a decrease in antioxidant defences, which is especially
      evident in cells with mutations associated with the most severe clinical
      phenotype. This is magnified by stressful conditions such as exposure to
      galactose.

PMID- 15720388
TI  - Cloning and expression of the first nonmammalian interleukin-11 gene in rainbow
      trout Oncorhynchus mykiss.
AB  - Interleukin (IL)-11 is a multifunctional cytokine that stimulates hematopoietic
      progenitor cells and exerts a series of important immunomodulatory effects. It
      was believed to be restricted to mammals, but here we report the first
      nonmammalian IL-11 gene, in rainbow trout (Oncorhynchus mykiss). A trout IL-11
      cDNA clone was isolated that contains a 5'-untranslated region (UTR) of 400 bp,
      an open reading frame of 612 bp and a large 3'-UTR of 1924 bp. Analysis of a
      genomic DNA clone from a trout lambda library revealed that the trout IL-11 gene
      has the same five exon/four intron gene organization, as well as the same intron
      phase, as mammalian IL-11 genes. The 204 amino acid trout IL-11 translation has a
      predicted signal peptide of 26 amino acids and mature peptide of 178 amino acids,
      with a calculated molecular mass of 20.5 kDa and a theoretical pI of 9.83. The
      mature peptide contains a cysteine residue and a potential N-linked glycosylation
      site that are not present in mammals. Phylogenetic analysis clearly grouped trout
      IL-11 with IL-11 molecules from other species and separated from other members of
      the IL-6 family. The IL-11 gene is highly expressed in intestine and gills in
      healthy fish and its expression can also be detected in spleen, head kidney,
      brain, skin and muscle. Bacterial infection of rainbow trout markedly up
      regulates IL-11 expression in liver, head kidney and spleen. IL-11 expression is
      also up-regulated in RTS-11 cells (a trout macrophage cell line), which
      constitutively expressed the lowest level of IL-11 of the four trout cell lines
      examined, after stimulation with bacteria, lipopolysaccharide, poly(I:C) and
      recombinant trout IL-1beta. Only a single transcript of 3.2 kb could be detected
      in lipopolysaccharide or recombinant IL-1beta-stimulated RNA samples by northern
      blotting. The expression results, showing that IL-11 is widely distributed and
      modulated by infection and other cytokines, suggest that fish IL-11 is an active
      player in the cytokine network and the host immune response to infection.

PMID- 15720389
TI  - Kinetic and binding studies with purified recombinant proteins ferredoxin
      reductase, ferredoxin and cytochrome P450 comprising the morpholine mono
      oxygenase from Mycobacterium sp. strain HE5.
AB  - The P450mor system from Mycobacterium sp. strain HE5, supposed to catalyse the
      hydroxylation of different N-heterocycles, is composed of three components:
      ferredoxin reductase (FdRmor), Fe3S4 ferredoxin (Fdmor) and cytochrome P450
      (P450mor). In this study, we purified Fdmor and P450mor as recombinant proteins
      as well as FdRmor, which has been isolated previously. Kinetic investigations of
      the redox couple FdRmor/Fdmor revealed a 30-fold preference for the NADH
      dependent reduction of nitroblue tetrazolium (NBT) and an absolute requirement
      for Fdmor in this reaction, compared with the NADH-dependent reduction of
      cytochrome c. The quite low Km (5.3 +/- 0.3 nm) of FdRmor for Fdmor, measured
      with NBT as the electron acceptor, indicated high specificity. The addition of
      sequences providing His-tags to the N- or C-terminus of Fdmor did not
      significantly alter kinetic parameters, but led to competitive background
      activities of these fusion proteins. Production of P450mor as an N-terminal His
      tag fusion protein enabled the purification of this protein in its spectral
      active form, which has previously not been possible for wild-type P450mor. The
      proposed substrates morpholine, piperidine or pyrrolidine failed to produce
      substrate-binding spectra of P450mor under any conditions. Pyridine, metyrapone
      and different azole compounds generated type II binding spectra and the Kd values
      determined for these substances suggested that P450mor might have a preference
      for more bulky and/or hydrophobic molecules. The purified recombinant proteins
      FdRmor, Fdmor and P450mor were used to reconstitute the homologous P450
      containing mono-oxygenase, which was shown to convert morpholine.

PMID- 15720390
TI  - Saccharomyces cerevisiae Ybr004c and its human homologue are required for
      addition of the second mannose during glycosylphosphatidylinositol precursor
      assembly.
AB  - Addition of the second mannose is the only obvious step in
      glycosylphosphatidylinositol (GPI) precursor assembly for which a responsible
      gene has not been discovered. A bioinformatics-based strategy identified the
      essential Saccharomyces cerevisiae Ybr004c protein as a candidate for the second
      GPI alpha-mannosyltransferase (GPI-MT-II). S. cerevisiae cells depleted of
      Ybr004cp have weakened cell walls and abnormal morphology, are unable to
      incorporate [3H]inositol into proteins, and accumulate a GPI intermediate having
      a single mannose that is likely modified with ethanolamine phosphate. These data
      indicate that Ybr004cp-depleted yeast cells are defective in second mannose
      addition to GPIs, and suggest that Ybr004cp is GPI-MT-II or an essential subunit
      of that enzyme. Ybr004cp homologues are encoded in all sequenced eukaryotic
      genomes, and are predicted to have 8 transmembrane domains, but show no obvious
      resemblance to members of established glycosyltransferase families. The human
      Ybr004cp homologue can substitute for its S. cerevisiae counterpart in vivo.

PMID- 15720391
TI  - Characterization of the Drosophila Methoprene -tolerant gene product. Juvenile
      hormone binding and ligand-dependent gene regulation.
AB  - Juvenile hormones (JHs) of insects are sesquiterpenoids that regulate a great
      diversity of processes in development and reproduction. As yet the molecular
      modes of action of JH are poorly understood. The Methoprene-tolerant (Met) gene
      of Drosophila melanogaster has been found to be responsible for resistance to a
      JH analogue (JHA) insecticide, methoprene. Previous studies on Met have
      implicated its involvement in JH signaling, although direct evidence is lacking.
      We have now examined the product of Met (MET) in terms of its binding to JH and
      ligand-dependent gene regulation. In vitro synthesized MET directly bound to JH
      III with high affinity (Kd = 5.3 +/- 1.5 nm, mean +/- SD), consistent with the
      physiological JH concentration. In transient transfection assays using Drosophila
      S2 cells the yeast GAL4-DNA binding domain fused to MET exerted JH- or JHA
      dependent activation of a reporter gene. Activation of the reporter gene was
      highly JH- or JHA-specific with the order of effectiveness: JH III >> JH II > JH
      I > methoprene; compounds which are only structurally related to JH or JHA did
      not induce any activation. Localization of MET in the S2 cells was nuclear
      irrespective of the presence or absence of JH. These results suggest that MET may
      function as a JH-dependent transcription factor.

PMID- 15720392
TI  - Missense mutations as a cause of metachromatic leukodystrophy. Degradation of
      arylsulfatase A in the endoplasmic reticulum.
AB  - Metachromatic leukodystrophy is a lysosomal storage disorder caused by a
      deficiency of arylsulfatase A (ASA). Biosynthesis studies of ASA with various
      structure-sensitive monoclonal antibodies reveal that some epitopes of the enzyme
      form within the first minutes of biosynthesis whereas other epitopes form later,
      between 10 and 25 min. When we investigated 12 various ASAs, with amino acid
      substitutions according to the missense mutations found in metachromatic
      leukodystrophy patients, immunoprecipitation with monoclonal antibodies revealed
      folding deficits in all 12 mutant ASA enzymes. Eleven of the 12 mutants show
      partial expression of the early epitopes, but only six of these show, in
      addition, incomplete expression of late epitopes. In none of the mutant enzymes
      were the late forming epitopes found in the absence of early epitopes. Thus, data
      from the wild-type and mutant enzymes indicate that the enzyme folds in a
      sequential manner and that the folding of early forming epitopes is a
      prerequisite for maturation of the late epitopes. All mutant enzymes in which the
      amino acid substitution prevents the expression of the late forming epitopes are
      retained in the endoplasmic reticulum (ER). In contrast, all mutants in which a
      single late epitope is at least partially expressed can leave the ER. Thus,
      irrespective of the missense mutation, the expression of epitopes forming late in
      biosynthesis correlates with the ability of the enzyme to leave the ER. The
      degradation of ER-retained enzymes can be reduced by inhibitors of the proteasome
      and ER alpha1,2-mannosidase I, indicating that all enzymes are degraded via the
      proteasome. Inhibition of degradation did not lead to an enhanced delivery from
      the ER for any of the mutant enzymes.

PMID- 15720393
TI  - Discovery and characterization of a Coenzyme A disulfide reductase from
      Pyrococcus horikoshii. Implications for this disulfide metabolism of anaerobic
      hyperthermophiles.
AB  - We have cloned NADH oxidase homologues from Pyrococcus horikoshii and P.
      furiosus, and purified the recombinant form of the P. horikoshii enzyme to
      homogeneity from Escherichia coli. Both enzymes (previously referred to as NOX2)
      have been shown to act as a coenzyme A disulfide reductases (CoADR: CoA-S-S-CoA +
      NAD(P)H + H+-->2CoA-SH + NAD(P)+). The P. horikoshii enzyme shows a kcat app of
      7.2 s(-1) with NADPH at 75 degrees C. While the enzyme shows a preference for
      NADPH, it is able to use both NADPH and NADH efficiently, with both giving
      roughly equal kcats, while the Km for NADPH is roughly eightfold lower than that
      for NADH. The enzyme is specific for the CoA disulfide, and does not show
      significant reductase activity with other disulfides, including dephospho-CoA.
      Anaerobic reductive titration of the enzyme with NAD(P)H proceeds in two stages,
      with an apparent initial reduction of a nonflavin redox center with the first
      reduction resulting in what appears to be an EH2 form of the enzyme. Addition of
      a second of NADPH results in the formation of an apparent FAD-NAD(P)H complex.
      The behavior of this enzyme is quite different from the mesophilic staphylococcal
      version of the enzyme. This is only the second enzyme with this activity
      discovered, and the first from a strict anaerobe, an Archaea, or
      hyperthermophilic source. P. furiosus cells were assayed for small molecular mass
      thiols and found to contain 0.64 micromol CoA.g dry weight(-1) (corresponding to
      210 microM CoA in the cell) consistent with CoA acting as a pool of disulfide
      reducing equivalents.

PMID- 15720394
TI  - Pulchellin, a highly toxic type 2 ribosome-inactivating protein from Abrus
      pulchellus. Cloning heterologous expression of A-chain and structural studies.
AB  - Pulchellin is a type 2 ribosome-inactivating protein isolated from seeds of the
      Abrus pulchellus tenuiflorus plant. This study aims to obtain active and
      homogeneous protein for structural and biological studies that will clarify the
      functional aspects of this toxin. The DNA fragment encoding pulchellin A-chain
      was cloned and inserted into pGEX-5X to express the recombinant pulchellin A
      chain (rPAC) as a fusion protein in Escherichia coli. The deduced amino acid
      sequence analyses of the rPAC presented a high sequential identity (> 86%) with
      the A-chain of abrin-c. The ability of the rPAC to depurinate rRNA in yeast
      ribosome was also demonstrated in vitro. In order to validate the toxic activity
      we promoted the in vitro association of the rPAC with the recombinant pulchellin
      binding chain (rPBC). Both chains were incubated in the presence of a
      reduced/oxidized system, yielding an active heterodimer (rPAB). The rPAB showed
      an apparent molecular mass of approximately 60 kDa, similar to the native
      pulchellin. The toxic activities of the rPAB and native pulchellin were compared
      by intraperitoneal injection of different dilutions into mice. The rPAB was able
      to kill 50% of the tested mice with doses of 45 microg x kg(-1). Our results
      indicated that the heterodimer showed toxic activity and a conformational pattern
      similar to pulchellin. In addition, rPAC produced in this heterologous system
      might be useful for the preparation of immunoconjugates with potential as a
      therapeutic agent.

PMID- 15720395
TI  - Structure and function comparison of Micropechis ikaheka snake venom
      phospholipase A2 isoenzymes.
AB  - Comparison of the crystal structures of three Micropechis ikaheka phospholipase
      A2 isoenzymes (MiPLA2, MiPLA3 and MiPLA4, which exhibit different levels of
      pharmacological effects) shows that their C-terminus (residues 110-124) is the
      most variable. M-Type receptor binding affinity of the isoenzymes has also been
      investigated and MiPLA4 binds to the rabbit M-type receptor with high affinity.
      Examination of surface charges of the isoenzymes reveals a trend of increase in
      positive charges with potency. The isoenzymes are shown to oligomerize in a
      concentration-dependent manner in a semi-denaturing gel. The C-termini of the
      medium (MiPLA4) and highly potent (MiPLA2) isoenzyme molecules cluster together,
      forming a highly exposed area. A BLAST search using the sequence of the most
      potent MiPLA2 results in high similarity to Staphylococcus aureus clotting factor
      A and cadherin 11. This might explain the myotoxicity, anticoagulant and
      hemoglobinuria effects of MiPLA2s.

PMID- 15720396
TI  - The male seahorse synthesizes and secretes a novel C-type lectin into the brood
      pouch during early pregnancy.
AB  - The male seahorse incubates its young in a manner resembling that of a mammalian
      pregnancy. After the female deposits her eggs into the male's brood pouch they
      are fertilized and the embryos develop and grow for several weeks until they are
      able to withstand the external environmental conditions independently, at which
      point they are irreversibly released. Although the precise function of the brood
      pouch is not clear, it is probably related to providing a suitable protective and
      osmotic environment for the young. The aim of this project was to construct and
      characterize a cDNA library made from the tissue lining the pouch, in order to
      help understand the molecular mechanisms regulating its development and function.
      The library profile indicates expression of genes encoding proteins involved in
      metabolism and transport, as well as structural proteins, gene regulatory
      proteins, and other proteins whose function is unknown. However, a large portion
      of the library contained genes encoding C-type lectins (CTLs), of which three
      full-length proteins were identified and found to contain a signal peptide and a
      single C-lectin domain, possessing all the conserved structural elements. We have
      produced recombinant protein for one of these and raised antisera; we have shown,
      using Western analysis and 2D electrophoresis, that this protein is secreted in
      significant quantities into the pouch fluid specifically during early pregnancy.
      Preliminary functional studies indicate that this CTL causes erythrocyte
      agglutination and may help to repress bacterial growth.

PMID- 15720398
TI  - Characterization of a eukaryotic type serine/threonine protein kinase and protein
      phosphatase of Streptococcus pneumoniae and identification of kinase substrates.
AB  - Searching the genome sequence of Streptococcus pneumoniae revealed the presence
      of a single Ser/Thr protein kinase gene stkP linked to protein phosphatase phpP.
      Biochemical studies performed with recombinant StkP suggest that this protein is
      a functional eukaryotic-type Ser/Thr protein kinase. In vitro kinase assays and
      Western blots of S. pneumoniae subcellular fractions revealed that StkP is a
      membrane protein. PhpP is a soluble protein with manganese-dependent phosphatase
      activity in vitro against a synthetic substrate RRA(pT)VA. Mutations in the
      invariant aspartate residues implicated in the metal binding completely abolished
      PhpP activity. Autophosphorylated form of StkP was shown to be a substrate for
      PhpP. These results suggest that StkP and PhpP could operate as a functional pair
      in vivo. Analysis of phosphoproteome maps of both wild-type and stkP null mutant
      strains labeled in vivo and subsequent phosphoprotein identification by peptide
      mass fingerprinting revealed two possible substrates for StkP. The evidence is
      presented that StkP can phosphorylate in vitro phosphoglucosamine mutase GlmM
      which catalyzes the first step in the biosynthetic pathway leading to the
      formation of UDP-N-acetylglucosamine, an essential common precursor to cell
      envelope components.

PMID- 15720397
TI  - The enantioselectivities of the active and allosteric sites of mammalian
      ribonucleotide reductase.
AB  - Here we examine the enantioselectivity of the allosteric and substrate binding
      sites of murine ribonucleotide reductase (mRR). L-ADP binds to the active site
      and L-ATP binds to both the s- and a-allosteric sites of mR1 with affinities that
      are only three- to 10-fold weaker than the values for the corresponding D
      enantiomers. These results demonstrate the potential of L-nucleotides for
      interacting with and modulating the activity of mRR, a cancer chemotherapeutic
      and antiviral target. On the other hand, we detect no substrate activity for L
      ADP and no inhibitory activity for N3-L-dUDP, demonstrating the greater
      stereochemical stringency at the active site with respect to catalytic activity.

PMID- 15720399
TI  - Characterization of cinnamyl alcohol dehydrogenase of Helicobacter pylori. An
      aldehyde dismutating enzyme.
AB  - Cinnamyl alcohol dehydrogenases (CAD; 1.1.1.195) catalyse the reversible
      conversion of p-hydroxycinnamaldehydes to their corresponding alcohols, leading
      to the biosynthesis of lignin in plants. Outside of plants their role is less
      defined. The gene for cinnamyl alcohol dehydrogenase from Helicobacter pylori
      (HpCAD) was cloned in Escherichia coli and the recombinant enzyme characterized
      for substrate specificity. The enzyme is a monomer of 42.5 kDa found
      predominantly in the cytosol of the bacterium. It is specific for NADP(H) as
      cofactor and has a broad substrate specificity for alcohol and aldehyde
      substrates. Its substrate specificity is similar to the well-characterized plant
      enzymes. High substrate inhibition was observed and a mechanism of competitive
      inhibition proposed. The enzyme was found to be capable of catalysing the
      dismutation of benzaldehyde to benzyl alcohol and benzoic acid. This dismutation
      reaction has not been shown previously for this class of alcohol dehydrogenase
      and provides the bacterium with a means of reducing aldehyde concentration within
      the cell.

PMID- 15720400
TI  - Identification and characterization of four novel peptide motifs that recognize
      distinct regions of the transcription factor CP2.
AB  - Although ubiquitously expressed, the transcriptional factor CP2 also exhibits
      some tissue- or stage-specific activation toward certain genes such as globin in
      red blood cells and interleukin-4 in T helper cells. Because this specificity may
      be achieved by interaction with other proteins, we screened a peptide display
      library and identified four consensus motifs in numerous CP2-binding peptides:
      HXPR, PHL, ASR and PXHXH. Protein-database searching revealed that RE-1 silencing
      factor (REST), Yin-Yang1 (YY1) and five other proteins have one or two of these
      CP2-binding motifs. Glutathione S-transferase pull-down and coimmunoprecipitation
      assays showed that two HXPR motif-containing proteins REST and YY1 indeed were
      able to bind CP2. Importantly, this binding to CP2 was almost abolished when a
      double amino acid substitution was made on the HXPR sequence of REST and YY1
      proteins. The suppressing effect of YY1 on CP2's transcriptional activity was
      lost by this point mutation on the HXPR sequence of YY1 and reduced by an HXPR
      containing peptide, further supporting the interaction between CP2 and YY1 via
      the HXPR sequence. Mapping the sites on CP2 for interaction with the four
      distinct CP2-binding motifs revealed at least three different regions on CP2.
      This suggests that CP2 recognizes several distinct binding motifs by virtue of
      employing different regions, thus being able to interact with and regulate many
      cellular partners.

PMID- 15720401
TI  - Cytosolic phospholipase A2-alpha and cyclooxygenase-2 localize to intracellular
      membranes of EA.hy.926 endothelial cells that are distinct from the endoplasmic
      reticulum and the Golgi apparatus.
AB  - Cytosolic phospholipase A2-alpha (cPLA2-alpha) is a calcium-activated enzyme that
      plays an important role in agonist-induced arachidonic acid release. In
      endothelial cells, free arachidonic acid can be converted subsequently into
      prostacyclin, a potent vasodilator and inhibitor of platelet activation, through
      the action of cyclooxygenase (COX) enzymes. Here we study the relocation of cPLA2
      alpha in human EA.hy.926 endothelial cells following stimulation with the calcium
      mobilizing agonist, A23187. Relocation of cPLA2-alpha was seen to be highly cell
      specific, and in EA.hy.926 cells occurred primarily to intracellular structures
      resembling the endoplasmic reticulum (ER) and Golgi. In addition, relocation to
      both the inner and outer surfaces of the nuclear membrane was observed.
      Colocalization studies with markers for these subcellular organelles, however,
      showed colocalization of cPLA2-alpha with nuclear membrane markers but not with
      ER or Golgi markers, suggesting that the relocation of cPLA2-alpha occurs to
      sites that are separate from these organelles. Colocalization with annexin V was
      also observed at the nuclear envelope, however, little overlap with staining
      patterns for the potential cPLA2-alpha interacting proteins, annexin I, vimentin,
      p11 or actin, was seen in this cell type. In contrast, cPLA2-alpha was seen to
      partially colocalize specifically with the COX-2 isoform at the ER-resembling
      structures, but not with COX-1. These studies suggest that cPLA2-alpha and COX-2
      may function together at a distinct and novel compartment for eicosanoid
      signalling.

PMID- 15720402
TI  - Isolation and characterization of a D-cysteine desulfhydrase protein from
      Arabidopsis thaliana.
AB  - In several organisms D-cysteine desulfhydrase (D-CDes) activity (EC 4.1.99.4) was
      measured; this enzyme decomposes D-cysteine into pyruvate, H2S, and NH3. A gene
      encoding a putative D-CDes protein was identified in Arabidopsis thaliana (L)
      Heynh. based on high homology to an Escherichia coli protein called YedO that has
      D-CDes activity. The deduced Arabidopsis protein consists of 401 amino acids and
      has a molecular mass of 43.9 kDa. It contains a pyridoxal-5'-phosphate binding
      site. The purified recombinant mature protein had a Km for D-cysteine of 0.25 mm.
      Only D-cysteine but not L-cysteine was converted by D-CDes to pyruvate, H2S, and
      NH3. The activity was inhibited by aminooxy acetic acid and hydroxylamine,
      inhibitors specific for pyridoxal-5'-phosphate dependent proteins, at low
      micromolar concentrations. The protein did not exhibit 1-aminocyclopropane-1
      carboxylate deaminase activity (EC 3.5.99.7) as homologous bacterial proteins.
      Western blot analysis of isolated organelles and localization studies using
      fusion constructs with the green fluorescent protein indicated an intracellular
      localization of the nuclear encoded D-CDes protein in the mitochondria. D-CDes
      RNA levels increased with proceeding development of Arabidopsis but decreased in
      senescent plants; D-CDes protein levels remained almost unchanged in the same
      plants whereas specific D-CDes activity was highest in senescent plants. In
      plants grown in a 12-h light/12-h dark rhythm D-CDes RNA levels were highest in
      the dark, whereas protein levels and enzyme activity were lower in the dark
      period than in the light indicating post-translational regulation. Plants grown
      under low sulfate concentration showed an accumulation of D-CDes RNA and
      increased protein levels, the D-CDes activity was almost unchanged. Putative in
      vivo functions of the Arabidopsisd-CDes protein are discussed.

PMID- 15720403
TI  - Neurobiology of the fruit fly's circadian clock.
AB  - Studying the fruit fly Drosophila melanogaster has revealed mechanisms underlying
      circadian clock function. Rhythmic behavior could be assessed to the function of
      several clock genes that generate circadian oscillations in certain brain
      neurons, which finally modulate behavior in a circadian manner. This review
      outlines how individual circadian pacemaker neurons in the fruit fly's brain
      control rhythm in locomotor activity and eclosion.

PMID- 15720404
TI  - Genetic modifiers of the Kv beta2-null phenotype in mice.
AB  - Shaker-type potassium (K+) channels are composed of pore-forming alpha subunits
      associated with cytoplasmic beta subunits. Kv beta2 is the predominant Kv beta
      subunit in the mammalian nervous system, but its functions in vivo are not clear.
      Kv beta2-null mice have been previously characterized in our laboratory as having
      reduced lifespans, cold swim-induced tremors and occasional seizures, but no
      apparent defect in Kv alpha-subunit trafficking. To test whether strain
      differences might influence the severity of this phenotype, we analyzed Kv beta2
      null mice in different strain backgrounds: 129/SvEv (129), C57BL/6J (B6) and two
      mixed B6/129 backgrounds. We found that strain differences significantly affected
      survival, body weight and thermoregulation in Kv beta2-null mice. B6 nulls had a
      more severe phenotype than 129 nulls in these measures; this dramatic difference
      did not reflect alterations in seizure thresholds but may relate to strain
      differences we observed in cerebellar Kv1.2 expression. To specifically test
      whether Kv beta1 is a genetic modifier of the Kv beta2-null phenotype, we
      generated Kv beta1.1-deficient mice by gene targeting and bred them to Kv beta2
      null mice. Kv beta1.1/Kv beta2 double knockouts had significantly increased
      mortality compared with either single knockout but still maintained surface
      expression of Kv1.2, indicating that trafficking of this alpha subunit does not
      require either Kv beta subunit. Our results suggest that genetic differences
      between 129/SvEv and C57Bl/6J are key determinants of the severity of defects
      seen in Kv beta2-null mice and that Kv beta1.1 is a specific although not strain
      dependent modifier.

PMID- 15720405
TI  - Where's my dinner? Adult neurogenesis in free-living food-storing rodents.
AB  - Postnatal hippocampal neurogenesis in wild mammals may play an essential role in
      spatial memory. We compared two species that differ in their reliance on memory
      to locate stored food. Yellow-pine chipmunks use a single cache to store winter
      food; eastern gray squirrels use multiple storage sites. Gray squirrels had three
      times the density of proliferating cells in the dentate gyrus (determined by Ki
      67 immunostaining) than that found in chipmunks, but similar density of young
      neurons (determined by doublecortin immunostaining). Three explanations may
      account for these results. First, the larger population of young cells in
      squirrels may increase the flexibility of the spatial memory system by providing
      a larger pool of cells from which new neurons can be recruited. Second, squirrels
      may have a more rapid cell turnover rate. Third, many young cells in the
      squirrels may mature into glia rather than neurons. The densities of young
      neurons were higher in juveniles than in adults of both species. The relationship
      between adult age and cell density was more complex than that has been found in
      captive populations. In adult squirrels, the density of proliferating cells
      decreased exponentially with age, whereas in adult chipmunks the density of young
      neurons decreased exponentially with age.

PMID- 15720406
TI  - Molecular correlates of emotional learning using genetically selected rat lines.
AB  - The genetic contributions to active avoidance learning in rodents have been well
      established, yet the molecular basis for genetically selected line differences
      remains poorly understood. To identify candidate genes influencing this active
      avoidance paradigm, we utilized the bidirectionally selected Syracuse high- and
      low-avoidance (SHA and SLA) rat lines that markedly differ in their two-way
      active avoidance behavior. Rats were phenotyped, rested to allow recovery from
      testing stress and then hippocampi were dissected for gene expression profiling
      (Affymetrix U34A chips; approximately 7000 known genes), comparing SLA to SHA.
      Next, a subset of differentially expressed genes was confirmed by real-time PCR
      (RT-PCR) in hippocampi. Additional studies at the protein level were performed
      for some genes. Using triplicate arrays on pooled hippocampal samples,
      differentially expressed genes were identified by microarray suite 5.0 and robust
      multi-array average analyses. By RT-PCR analysis in hippocampi, eight genes were
      nominated as potential candidate genes consistent with the differential
      expression from the microarray data. Four genes, Veli1 (mlin-7B), SLC3a1, Ptpro
      and Ykt6p, showed higher expression in SHA hippocampi than SLA. Four genes,
      SLC6A4, Aldh1a4, Id3a and Cd74, showed higher expression in SLA hippocampi than
      SHA. The active avoidance behavioral difference between lines probably emerges
      from 'many small things'. These potential candidate genes generate hypotheses for
      future testing in human association and rodent studies. Differences in levels of
      a pleiotropic gene like Ptpro and SLC6A4 suggest that small differences over a
      lifespan may contribute to large behavioral differences.

PMID- 15720407
TI  - Sensitivity to psychostimulants in mice bred for high and low stimulation to
      methamphetamine.
AB  - Methamphetamine (MA) and cocaine induce behavioral effects primarily through
      modulation of dopamine neurotransmission. However, the genetic regulation of
      sensitivity to these two drugs may be similar or disparate. Using selective
      breeding, lines of mice were produced with extreme sensitivity (high MA
      activation; HMACT) and insensitivity (low MA activation; LMACT) to the locomotor
      stimulant effects of acute MA treatment. Studies were performed to determine
      whether there is pleiotropic genetic influence on sensitivity to the locomotor
      stimulant effect of MA and to other MA- and cocaine-related behaviors. The HMACT
      line exhibited more locomotor stimulation in response to several doses of MA and
      cocaine, compared to the LMACT line. Both lines exhibited locomotor sensitization
      to 2 mg/kg of MA and 10 mg/kg of cocaine; the magnitude of sensitization was
      similar in the two lines. However, the lines differed in the magnitude of
      sensitization to a 1 mg/kg dose of MA, a dose that did not produce a ceiling
      effect that may confound interpretation of studies using higher doses. The LMACT
      line consumed more MA and cocaine in a two-bottle choice drinking paradigm; the
      lines consumed similar amounts of saccharin and quinine, although the HMACT line
      exhibited slightly elevated preference for a low concentration of saccharin.
      These results suggest that some genes that influence sensitivity to the acute
      locomotor stimulant effect of MA have a pleiotropic influence on the magnitude of
      behavioral sensitization to MA and sensitivity to the stimulant effects of
      cocaine. Further, extreme sensitivity to MA may protect against MA and cocaine
      self-administration.

PMID- 15720410
TI  - Aggressive B-cell lymphomas: a review based on the workshop of the XI Meeting of
      the European Association for Haematopathology.
AB  - The generic term aggressive B-cell lymphoma includes a variety of entities, each
      with particular diagnostic and therapeutic issues. To define these entities
      better and to help confront such issues, a workshop was organized by the European
      Association of Haematopathology (EAHP) and the Society of Haematology during the
      XI Meeting of the EAHP, held in Italy in May 2002. Participants were asked to
      submit cases under various categories and all cases submitted were examined and
      reviewed by the panel members. The panel's diagnoses formed the basis for
      discussion at the workshop and a limited number of cases were selected to be
      presented in more detail and discussed during the workshop. After the workshop
      the panel met again to discuss the outcome, summarized in this report, which
      describes the panel's proposals regarding diagnostic criteria, terminology, the
      definition of new entities and evaluation of biological differential and new
      prognostic parameters.

PMID- 15720411
TI  - Expression of S100 proteins in normal human tissues and common cancers using
      tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in
      common cancers.
AB  - AIMS: To survey the expression of members of the S100 family of calcium-binding
      proteins in normal human tissues and common cancers using tissue microarrays.
      S100A6, S100A8, S100A9 and S100A11 have all been suggested to have potential
      roles in carcinogenesis and tumour progression but their expression has not been
      described in a wide range of human tissues and tumours. METHODS AND RESULTS: A
      custom-made tissue array, containing 291 tissue cores representing 28 tissue
      types and 21 tumour types, was used to produce sections that were immunostained
      for S100A2, S100A6, S100A8, S100A9, S100A11, calbindin 1, calbindin 2, S100B and
      parvalbumin. S100A6, S100A8 and S100A9 were expressed in 32%, 12% and 28% of
      breast cancers, respectively. There was a translocation of S100A11 expression
      from exclusively nuclear in normal tissues to cytoplasmic and nuclear in all
      common cancers. CONCLUSIONS: S100A6, S100A8, S100A9 and S100A11 are all expressed
      in common cancers, especially breast cancer. In addition, S100A11 undergoes a
      nucleocytoplasmic translocation which may have a direct influence on the
      proliferation of the cancer cells.

PMID- 15720412
TI  - The expression of p53 and bcl-2 in gastrointestinal stromal tumours is associated
      with anatomical site, and p53 expression is associated with grade and clinical
      outcome.
AB  - AIMS: To compare the expression of p53 and bcl-2 in gastrointestinal stromal
      tumours (GISTs) with anatomical site, National Institutes of Health (NIH) risk
      category (grade), pathological features, and clinical outcome. METHODS AND
      RESULTS: The immunohistochemical expression of p53 and bcl-2 in 105 GISTs (71
      gastric, 20 small intestinal, four colonic, 10 rectal) was recorded. When all
      GISTs were assessed, there was p53 positivity in 28% and bcl-2 positivity in 77%.
      Gastric tumours had a lower prevalence of p53 positivity (20%) than intestinal
      (40-50%). Rectal GISTs had the lowest prevalence of bcl-2 positivity (20%) and
      gastric and small intestinal the highest (80% and 90%, respectively). In GISTs
      from all sites, p53 positivity was associated with size > 50 mm, epithelioid cell
      shape, nuclear atypia, mucosal invasion, and mitotic count > 5/50 high-power
      fields. In gastric GISTs the associations were the same, apart from size and
      mitotic count. In GISTs from all sites and in gastric GISTs, p53 expression
      correlated with NIH risk category. When GISTs from all sites were subjected to
      univariate survival analysis, an adverse outcome was associated with p53
      positivity, NIH risk category, and several established prognostic factors. When
      gastric GISTs were assessed, the associations were similar although size was not
      prognostic. In multivariate survival analysis, p53 expression was independently
      prognostic for gastric GISTs in some models, while it was never independently
      prognostic for GISTs from all sites. Whether all GISTs or gastric GISTs were
      assessed, bcl-2 showed no association with clinical outcome or risk category.
      CONCLUSIONS: Anatomical site influences p53 and bcl-2 expression in GISTs. p53
      expression is associated with NIH risk category, various pathological features,
      and clinical outcome, and may be independently prognostic for gastric GISTs. Bcl
      2 expression has no prognostic value.

PMID- 15720413
TI  - Mucosal expression of cyclooxygenase isoforms 1 and 2 is increased with worsening
      damage to the gastric mucosa.
AB  - AIMS: To test the hypothesis that both COX-1 and COX-2 expression in human
      gastric mucosa is up-regulated in the presence of inflammation as seen in
      patients with gastritis and gastric ulcers. METHODS AND RESULTS: We performed
      immunohistochemistry using COX-1 and COX-2 monoclonal antibodies on gastric
      biopsies from 59 patients with normal mucosa, gastritis and gastric ulcers.
      Expression of COX-1 and COX-2 was quantified using an intensity proportion
      scoring system. Expression of COX-1 was primarily seen in the lamina propria
      mononuclear cells with some expression in deep gastric glands in the ulcer group.
      Expression of COX-2 was primarily seen in the deep gastric glands with focal
      expression in the lamina propria mononuclear cells. We found a stepwise increase
      in the expression of both COX-1 and COX-2 as mucosal damage progressed from
      normal to gastritis to gastric ulcer. CONCLUSIONS: We conclude that both COX-1
      and COX-2 expression in the gastric mucosa are increased in the setting of
      gastritis and gastric ulceration. Although this increased expression may be due,
      at least in part, to an increase in inflammatory cell numbers, this study raises
      the possibility that both COX-1 and COX-2 are inducible, contrary to the
      traditionally held view of only COX-2 being inducible.

PMID- 15720414
TI  - Association between cyclooxygenase-2-expressing macrophages, ulceration and
      microvessel density in colorectal cancer.
AB  - AIM: In colorectal carcinomas, cyclooxygenase-2 (COX-2) is expressed
      predominantly by epithelial cells and is implicated in tumour progression. Tumour
      associated macrophages may influence tumour growth, proliferative rate and
      angiogenesis and also express COX-2 when activated. Thus they may play an
      important stromal-epithelial role in carcinogenesis. Tauhe aim of this study was
      to define the relationship between microvessel density (MVD), tumour COX-2 and
      macrophage COX-2 expression. METHODS AND RESULTS: Sixty-five cases of formalin
      fixed paraffin-embedded colorectal cancer were included in the study. Tissues
      were immunostained for COX-2, CD68 (macrophage marker) and CD34 (endothelial
      marker to assess MVD). Thirty-six cases were grossly ulcerated cancers and 29
      cases showed focal/microscopic ulceration. Macrophages were in high concentration
      at the base of ulcerated areas, and were also diffusely dispersed within tumoral
      stroma. However, the pattern of macrophage COX-2 expression revealed two
      populations of macrophages--those deep within the tumour (negative for COX-2) and
      those at the base of ulcers (positive for COX-2). In all cases, the tumour
      epithelial cells expressed COX-2. MVD was higher at the base of ulcers, adjacent
      to COX-2+ macrophages, and was lower deep within the tumour. CONCLUSIONS: In
      colorectal cancers, macrophages may have a dual role. Those concentrated at the
      base of the ulcers, where there is an associated high MVD, may induce
      angiogenesis, but their function may be in a healing/repair process. The lack of
      COX-2+ macrophages and lower MVD deep within the tumour suggests that it may be
      the epithelial COX-2 component that is important in tumour progression.

PMID- 15720415
TI  - Histopathology of carotid body in heroin addiction. Possible chemosensitive
      impairment.
AB  - AIMS: To perform a morphometric analysis of carotid bodies in opiate addicts.
      METHODS AND RESULTS: Carotid bodies were sampled at autopsy from 35 subjects who
      died of heroin intoxication (mean age 26 years), and from eight young (22 years)
      and eight older subjects (66.5 years) who died of trauma. Sections were stained
      with haematoxylin-eosin, azan-Mallory, and double-labelling immunohistochemistry
      with antineuronal specific enolase and anti-S100, to count type I and type II
      cells. Interlobular and intralobular connective tissue was increased both in the
      opiate cases (43.45 +/- 6.79%, P < 0.001, and 13.34 +/- 5.72%, P < 0.001,
      respectively) and older cases (46.67 +/- 1.65%, P < 0.001, and 9.62 +/- 2.11%, P
      < 0.05, respectively) compared with young cases (33.17 +/- 6.41% and 4.33 +/-
      1.84%, respectively). The percentage of type II cells in the opiate cases (51.6
      +/- 7.3%, P < 0.001) and in the older controls (49.0 +/- 7.2%, P < 0.01) was
      higher than in the young cases (37.9 +/- 3.0%). Among type I cells, the light
      cell percentage in the opiate cases (65.85 +/- 11%, P < 0.001) was reduced with
      respect to the two control groups (82.8 +/- 5.34%, young; 81.62 +/- 8.58%,
      older). CONCLUSIONS: The increases in connective tissue and type II cells are
      similar to findings in ageing and chronic pulmonary disease, and may be ascribed
      to glomic hypoxia. A direct action of opiates should be taken into account for
      the decrease in light cells in heroin addiction. The histopathological changes in
      the carotid body, by impairing chemosensivity, may play a role in the fatal
      cardiorespiratory derangement of heroin addicts.

PMID- 15720416
TI  - Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a
      tissue microarray and clinicopathological analysis.
AB  - AIMS: To assess, in tissue microarray (TMA), the proliferative activity of
      endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins
      (MCM7), and to explore its potential value for prognosis. MCM proteins are
      essential for eukaryotic DNA replication and have recently been used to define
      the proliferative compartments in human tissues. METHODS AND RESULTS:
      Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212
      cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according
      to the extent of nuclear staining. An analysis was carried out of the association
      between MCM7 expression and that of Ki67 and the clinicopathological
      characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was
      clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in
      endometrial carcinomas correlated with each other (P < 0.001). A significant
      correlation existed between the MCM7 labelling index and histological grade (P =
      0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas
      and younger patients had a lower MCM7 index. Poor survival was observed in
      patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7
      was found to be an independent prognostic factor by multivariate analysis (P =
      0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but
      had no significant prognostic impact (P = 0.50). CONCLUSIONS: In this TMA study
      on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker
      than Ki67 in assessing tumour proliferation and in the prognosis of patients.

PMID- 15720417
TI  - The distribution of cardiac macrophages in myocardial ischaemia and
      cardiomyopathy.
AB  - AIMS: Recent evidence has implicated the macrophage as an effector cell in the
      inflammatory processes in transplant rejection, as well as cardiac disease,
      including coronary atherosclerosis. Although the latter is a vascular disease,
      the entire myocardium is affected. We have previously demonstrated the presence
      and distribution of macrophages in the 'normal' human heart. In this paper the
      distribution of myocardial macrophages, in the various chambers of the failing
      human heart, from cases of coronary atheroma and cardiomyopathy undergoing heart
      transplantation is documented. METHODS AND RESULTS: Tissue blocks were removed at
      specific sites taken from six cases with ischaemic heart disease (IHD) (four
      males, two females, age range 54-62 years), and four cases with idiopathic
      dilated cardiomyopathy (IDCM) (three males, one female, age range 18-49 years).
      These were compared with hearts from five cases of sudden death, unrelated to
      heart disease. Sections were stained with a CD68 pan macrophage marker. Positive
      cells were enumerated in 20 random fields. Results were analysed using a
      generalized linear modelling method using a Poisson distribution. Macrophages
      were identified within the interstitium and often close to blood vessels in all
      hearts. Macrophages from IHD hearts demonstrated the most intense staining and
      were often larger and more elongated than those found in 'normal' control hearts.
      Macrophages were also often degranulated and staining was diffuse in the
      interstitium. Overall, there were significantly more macrophages in most areas
      from IHD hearts than from IDCM hearts or control hearts (P < 0.001). CONCLUSIONS:
      Significantly more macrophages were found in all four chambers in diseased hearts
      compared with controls. Macrophage numbers were higher in the atria than in
      ventricles in the diseased myocardium. This study suggests selective recruitment
      of macrophages into the atria in the disease states studied.

PMID- 15720418
TI  - Needle core biopsy can reliably distinguish between benign and malignant
      papillary lesions of the breast.
AB  - AIMS: To review 21 screen-detected papillary lesions in which the core biopsy
      findings suggested a papillary lesion and to correlate pathological and
      radiological findings in order to assess the risks of associated malignancy and
      the need for surgical intervention. The appropriate management of non-malignant
      papillary breast lesions detected on needle core biopsy (NCB) is currently
      uncertain. METHODS AND RESULTS: Forty-seven papillary breast lesions with a
      histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia
      (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, 'papillomatosis'
      or papillary carcinoma (invasive or in situ) were identified from records at the
      Leeds Breast Screening and Assessment Unit. The cases were diagnosed between
      between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary
      proliferation which had been categorized as either 'B2', benign, 'B3', of
      uncertain malignant potential, or 'B4', suspicious of malignancy. All of the 19
      'B3' or 'B4' cases and one of the two 'B2' lesions had undergone open surgical
      biopsy. All cases with a previous 'B4' were malignant on subsequent excision. All
      excised cases with a previous 'B3' or 'B2' were found benign, although four of
      the 'B3's derived from papillomata associated with an atypical proliferation
      amounting to ADH. In three of these four (75%) the papillary proliferation had
      been associated with epithelial hyperplasia of usual type (HUT) on the core and
      the radiological features were of a mass lesion detected on incident round screen
      which had increased in size. CONCLUSION: Our results confirm the accuracy of NCB
      in the diagnosis of screen-detected papillary lesions of the breast. Surgical
      excision may not always be necessary following a 'B3' core biopsy.

PMID- 15720419
TI  - CD10 and Bcl-2 expression combined with the International Prognostic Index can
      identify subgroups of patients with diffuse large-cell lymphoma with very good or
      very poor prognoses.
AB  - AIMS: Diffuse large B-cell lymphoma (DLBCL) is characterized by marked biological
      heterogeneity. The identification of reproducible parameters that can be combined
      with the International Prognostic Index (IPI) to better predict outcome could
      lead to the development of effective risk-adaptive strategies. METHODS AND
      RESULTS: Bcl-2 and CD10 expression was determined by immunohistochemistry. The
      impact of the positivity on survival was evaluated in combination with the IPI in
      86 patients with a confirmed diagnosis of DLBCL. Patients were divided according
      to the IPI into low-risk (no to two factors) or high-risk (three to five factors)
      groups. Positivity rates were 25% for CD10 and 42% for Bcl-2. In a Cox analysis,
      the high-risk IPI group [hazard ratio (HR) 5.98, P < 0.0001) and Bcl-2 expression
      (HR 2.43, P = 0.02) were independent poor prognostic factors, and expression of
      CD10 (HR 0.41, P = 0.052) predicted a favourable outcome. Among patients in the
      low-risk IPI group, CD10 positivity was associated with an excellent 8-year
      overall survival (92% versus 45%, P = 0.06). In the high-risk IPI group, Bcl-2
      positivity identified a subgroup with invariably fatal disease. CONCLUSIONS: The
      expression of CD10 in the low-risk IPI group, and the expression of Bcl-2 in the
      high-risk IPI group can identify two subgroups of patients who might benefit from
      new risk-adaptive treatment approaches.

PMID- 15720420
TI  - Gene expression profile identifies a rare epithelioid variant case of pleomorphic
      liposarcoma carrying FUS-CHOP transcript.
AB  - AIMS: To describe a tumour with morphological and immunophenotypic
      characteristics of epithelioid variant of pleomorphic liposarcoma. Pleomorphic
      liposarcoma is a very rare variant of liposarcoma defined morphologically by the
      presence of pleomorphic lipoblasts showing peculiar epithelial-like features that
      can be confused with primary or metastatic carcinoma. METHODS AND RESULTS:
      Molecular analysis demonstrated for the first time the presence of FUS-CHOP
      transcript in this liposarcoma variant. Microarray analysis revealed a gene
      expression profile related to a more aggressive tumour type when compared with
      other myxoid/round cell liposarcomas. CONCLUSIONS: The present data show that the
      epithelioid variant of pleomorphic liposarcoma represents a further variant of
      myxoid liposarcoma sharing the FUS-CHOP fusion transcript but carrying a distinct
      expression profile, in keeping with its aggressive clinical course.

PMID- 15720421
TI  - Nasopharyngeal carcinoma mimicking large-cell anaplastic lymphoma.

PMID- 15720423
TI  - Location of calcifying fibrous pseudotumour: peritoneal predominance.

PMID- 15720424
TI  - Microglandular hyperplasia: a pitfall in the diagnosis of microglandular type
      endometrioid adenocarcinoma.

PMID- 15720425
TI  - Incidental oral plasmablastic lymphoma with aberrant expression of CD4 in an
      elderly HIV-negative patient: how a gingival polyp can cause confusion.

PMID- 15720426
TI  - Detection of the Philadelphia chromosome in the iris of a child with acute
      lymphoblastic leukaemia.

PMID- 15720427
TI  - Does idiopathic granulomatous gastritis exist?

PMID- 15720428
TI  - Neutropenic enterocolitis in acute myeloblastic leukaemia.

PMID- 15720429
TI  - Solid and papillary epithelial neoplasm of the pancreas with ossification: a
      report of two cases.

PMID- 15720430
TI  - Sclerotic lipoma in a female patient.

PMID- 15720433
TI  - Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7
      cells also involves c-rel transcription factor.
AB  - Interleukin-10 (IL-10) is known to inhibit IL-12 production in macrophages
      primarily at the transcriptional level with the involvement of p50 and p65
      nuclear factor-kappaB (NF-kappaB). We demonstrate that the c-rel transcription
      factor also plays a major role in IL-10-mediated IL-12 suppression. Treatment of
      macrophages with recombinant IL-10 inhibited nuclear c-rel levels, whereas
      addition of neutralizing anti-IL-10 antibody up-regulated both nuclear c-rel
      levels and IL-12 production by macrophages. Decreased nuclear c-rel was
      associated with a reduction in phosphorylation of inhibitory kappa B alpha
      (IkappaBalpha) in the cytoplasm, indicating that IL-10 prevents degradation of
      IkappaBalpha and the subsequent translocation of c-rel into the nucleus.
      Treatment with leptomycin B, a known inhibitor of c-rel at a concentration of 10
      nm, when used with anti-IL-10 antibody, resulted in reduced expression of IL-12.
      In a complementary experiment, in vitro transient expression of p65 NF-kappaB
      could not rescue the inhibitory effect of IL-10 on IL-12 production, suggesting
      that NF-kappaB alone was not sufficient to restore IL-12 production during IL-10
      treatment. However, over-expression of c-rel resulted in IL-12 restoration upon
      stimulation with lipopolysaccharide plus interferon-gamma during IL-10 treatment.
      Our studies highlight the involvement of c-rel in IL-10-mediated IL-12
      regulation.

PMID- 15720432
TI  - Signal transducer and activator of transcription (STAT) signalling and T-cell
      lymphomas.
AB  - Interaction of cytokines with their cognate receptors leads to the activation of
      latent transcription factors - the signal transducers and activators of
      transcription (STAT) proteins - whose biological activities ultimately regulate
      many critical aspects of cell growth, survival and differentiation. Dysregulation
      of the JAK-STAT pathway is frequently observed in many primary human tumours,
      reflecting the importance of this pathway in the maintenance of cellular
      integrity. Here we review the current progress in STAT structure and function,
      and the contribution of STAT signalling to the pathogenesis of T-cell lymphomas.

PMID- 15720435
TI  - Natural killer T-cell populations in C57BL/6 and NK1.1 congenic BALB.NK mice-a
      novel thymic subset defined in BALB.NK mice.
AB  - Natural killer (NK) T lymphocytes are a subpopulation of T lymphocytes regarded
      as early regulators of immune responses. The majority of NKT cells are restricted
      by the CD1d molecule. NKT cells have mostly been studied in one single mouse
      strain, C57BL/6 (B6), because of the absence of NK1.1 in other common mouse
      strains, and the lack of other reliable surface markers for CD1d-restricted
      cells. To investigate NKT cell subsets in a mouse strain of a genetic background
      different from B6, we have back-crossed the NKT cell marker NK1.1 from the B6
      mouse to the BALB/c mouse strain. We show that NKT cells in the congenic BALB.B6
      NK1.1(b) mouse share many characteristics with their B6 counterparts, but seem to
      be deficient in the functional NKT cell subtype characterized by low interleukin
      4 and high interferon-gamma production, and surface expression of CD49b but not
      CD69. Moreover, in the thymus but not the spleen of BALB.B6-NK1.1(b) mice we find
      a novel Valpha14-Jalpha18 invariant NKT cell subset which is devoid of a set of
      NK markers, suggesting that these cells represent a less differentiated NKT cell
      stage, and carries high levels of the T-cell receptor and uses a skewed T-cell
      receptor Vbeta-repertoire.

PMID- 15720434
TI  - Interleukin-7 signalling is sufficient to phenotypically and functionally prime
      human CD4 naive T cells.
AB  - Interleukin-7 (IL-7) is produced by bone marrow and lymphoid stromal cells and is
      involved in the synthesis, survival and homeostasis of T cells. These attributes
      are the basis for current strategies to utilize IL-7 as an immune modulator for
      several clinical conditions to replenish depleted T-cell numbers. Because we had
      previously determined that IL-7 can induce potent human immunodeficiency virus
      replication in the otherwise non-permissive CD4(+) naive T-cell compartment, we
      evaluated here the impact of IL-7 on the phenotype and functional potential of
      naive CD4(+) T cells in an attempt to understand the mechanism of this induction.
      We demonstrate that IL-7 mediated the up-regulation of CD25, CD95 and human
      leucocyte antigen-DR, while it did not alter the expression of CD45RO, CD69,
      CD40, or CD154. Examination of the cytokine profile of IL-7-treated naive T cells
      using a Type1/Type2 Proteome Array indicated a remarkable IL-7-mediated induction
      of interferon-gamma production, while the other cytokines evaluated (IL-2, IL-12,
      tumour necrosis factor-alpha, IL-4, IL-5, IL-10 and IL-13) were not affected.
      Intracellular staining of IL-7-treated naive T cells for interferon-gamma
      verified the Proteome data. IL-7 did not induce cell cycle proliferation of naive
      CD4(+) T cells, as evaluated by 7-AAD/pyronin immunostaining and
      carboxyfluorescein diacetate succinimidyl ester dye tracking. IL-7 treatment of
      naive CD4(+) T cells induced their ability to prime monocytes, as was indicated
      by induction of CD80 and CD86 expression on monocytes cocultured with IL-7
      treated naive CD4(+) T cells. Collectively, these data indicate that IL-7
      signalling is sufficient to phenotypically and functionally prime human CD4(+)
      naive T cells independent of antigen stimulation.

PMID- 15720436
TI  - Stoichiometric tapasin interactions in the catalysis of major histocompatibility
      complex class I molecule assembly.
AB  - The assembly of major histocompatibility complex (MHC) class I molecules with
      their peptide ligands in the endoplasmic reticulum (ER) requires the assistance
      of many proteins that form a multimolecular assemblage termed the 'peptide
      loading complex'. Tapasin is the central stabilizer of this complex, which also
      includes the transporter associated with antigen processing (TAP), MHC class I
      molecules, the ER chaperone, calreticulin, and the thiol-oxidoreductase ERp57. In
      the present report, we investigated the requirements of these interactions for
      tapasin protein stability and MHC class I dissociation from the peptide-loading
      complex. We established that tapasin is stable in the absence of either TAP or
      MHC class I interaction. In the absence of TAP, tapasin interaction with MHC
      class I molecules is long-lived and results in the sequestration of existing
      tapasin molecules. In contrast, in TAP-sufficient cells, tapasin is re-utilized
      to interact with and facilitate the assembly of many MHC class I molecules
      sequentially. Furthermore, chemical cross-linking has been utilized to
      characterize the interactions within this complex. We demonstrate that tapasin
      and MHC class I molecules exist in a 1 : 1 complex without evidence of higher
      order tapasin multimers. Together these studies shed light on the tapasin protein
      life cycle and how it functions in MHC class I assembly with peptide for
      presentation to CD8(+) T cells.

PMID- 15720438
TI  - LAG-3 (CD223) reduces macrophage and dendritic cell differentiation from monocyte
      precursors.
AB  - Major histocompatibility complex (MHC) class II molecules expressed on monocytes
      may play a role in the control of differentiation of antigen-presenting cells. A
      soluble LAG-3 (CD223) molecule (sLAG-3) is a natural, high-affinity ligand for
      MHC class II. It is known to induce maturation of monocyte-derived dendritic
      cells in vitro and is used as a vaccine adjuvant to induce CD4 T helper type 1
      responses and CD8 T-cell responses in vivo. Here, we demonstrate that sLAG-3 (but
      not an MHC class II-specific monoclonal antibody) reduces the differentiation of
      monocytes into macrophages in the presence of granulocyte-macrophage colony
      stimulating factor (GM-CSF) as well as their differentiation into dendritic cells
      in the presence of GM-CSF and interleukin-4, as shown by a decrease in CD14 and
      CD1a expression, respectively. Dendritic cells derived from monocytes in the
      presence of sLAG-3 showed impaired antigen-presentation function, as assessed by
      the reduced capability to induce proliferation of T cells. Our results suggest
      that activated LAG-3(+) lymphocytes present at sites of inflammation may reduce
      the differentiation of monocytes into macrophages or fully competent antigen
      presenting dendritic cells, thus limiting the magnitude of the ongoing T-cell
      immune responses.

PMID- 15720437
TI  - Cross-linking of neutrophil CD11b results in rapid cell surface expression of
      molecules required for antigen presentation and T-cell activation.
AB  - Recent studies suggest that neutrophils may play a role in antigen presentation.
      In support of this hypothesis it has been shown that these cells appear to
      contain cytoplasmic stores of molecules required for this function, i.e. major
      histocompatibility complex class II (DR) antigen, CD80 and CD86. In this study we
      have considered a mechanism for the translocation of these preformed molecules
      onto the cell surface which does not require active synthesis. Cross-linking of
      the Mac-1 molecule (CD18 + CD11b) was shown to result in rapid cell surface
      expression of CD80, CD86 and DR antigen on the surface of normal human peripheral
      blood neutrophils. A distinct subpopulation (approximately 20%) of neutrophils
      appeared to be enlarged and were found to express significantly elevated levels
      of these molecules on the cell surface following cross-linking of CD11b when
      compared with control cells. The level of expression of CD80, CD86 and DR antigen
      on these large cells was comparable to, and in some cases greater than, the
      levels found expressed on the surface of monocytes obtained from the same donors.
      In addition, these cytoplasmic molecules were shown by confocal laser microscopy
      and by immunoelectron microscopy to be located within secretory vesicles.
      Following rapid translocation onto the cell surface, CD80 and CD86 appeared to be
      colocalized within large clusters reminiscent of the supramolecular antigen
      clusters previously found on conventional antigen-presenting cells. These
      findings therefore lend further support for the hypothesis that neutrophils may
      have a role to play in antigen presentation and/or T-cell activation.

PMID- 15720439
TI  - Migration of polymorphonuclear leucocytes is influenced by dendritic cells.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells and populate
      many tissues where they may participate in inflammatory reactions. The
      infiltration of polymorphonuclear leucocytes (PMNLs) into tissues is a prominent
      feature of inflammation. The mechanisms of PMNL recruitment depend on chemotactic
      factors and adhesion molecules expressed on endothelial cells. The aim of the
      present study was to determine whether DCs participate in the early recruitment
      of PMNLs. Dendritic cells derived from peripheral blood monocytes were used for
      this study. PMNLs incubated with culture supernatant (CS) from untreated or from
      tumour necrosis factor-alpha (TNF-alpha)-treated (1 hr, 100 U/ml, 37 degrees )
      monocyte-derived DCs (moDCs) had increased surface expression of both CD11b and
      CD18. Moreover, both untreated and TNF-alpha-treated moDCs induced PMNL
      chemotaxis. By blocking CXCL8, CXCL5, CXCL7 and Pan GRO (CXCL1, CXCL2, CXCL3), we
      observed that CXCL8/interleukin-8 might be the chemokine that induced the PMNL
      chemotactic activity in the CS of untreated and TNF-alpha-treated moDC.
      Furthermore, we investigated the regulation of CXCL8 production in moDCs by
      adhesion molecule engagement. Our data demonstrated that CD31, CD18, CD29 and
      CD49d participated in the adhesion of immature moDCs to endothelium. Moreover,
      engagement of domains 1-3 of CD31, but not of CD29 or CD18, decreased the
      production of CXCL8 by immature but not mature moDCs (which display lower CD31
      levels than immature moDCs). Overall, these results suggest that DCs not only
      trigger a specific immune response, but also the innate immune response by
      recruiting PMNLs. Furthermore, our results also suggest that CXCL8 production by
      immature DCs might be regulated by signalling through CD31 during their migration
      through the vascular endothelium.

PMID- 15720440
TI  - Haemopoietic mechanisms in murine allergic upper and lower airway inflammation.
AB  - Eosinophil recruitment to the airways, including involvement of haemopoietic
      eosinophil-basophil progenitors (Eo/B-CFU), is primarily regulated by interleukin
      5 (IL-5) and eotaxin. In this study, we investigated the haemopoietic mechanisms
      in upper and lower airway eosinophilic inflammation. Ovalbumin (OVA) sensitized
      and challenged BALB/c mice were used to establish isolated upper (UAC), isolated
      lower (LAC), or combined upper and lower airway (ULAC) inflammation. Airway,
      blood and bone marrow responses were evaluated in each model. Numbers of airway
      eosinophils and CD4(+) cells were increased significantly in the nasal mucosa in
      UAC and ULAC mice, and in the lung tissue in LAC and ULAC groups. Levels of IL-5
      and eotaxin were increased significantly in the nasal lavage fluid (NL) in UAC
      and ULAC mice, and in the bronchoalveolar lavage fluid (BAL) in LAC and ULAC
      groups. The proportion of IL-5-responsive bone marrow Eo/B-CFU was significantly
      higher than the control in all treatment groups, but peaked much earlier in the
      ULAC group. Kinetic studies revealed that IL-5 and eotaxin in NL, BAL and serum
      peaked between 2 and 12 hr after OVA challenge in ULAC mice, and at 24 hr in UAC
      mice, related to the timing of maximal progenitor responses. These data support
      the concept that the systemic mechanisms linking rhinitis to asthma depend on the
      location and extent of airway allergen exposure.

PMID- 15720441
TI  - Antithetical effects of hemicellulase-treated Agaricus blazei on the maturation
      of murine bone-marrow-derived dendritic cells.
AB  - We report the effects of hemicellulase-treated Agaricus blazei (ABH) on the
      maturation of bone-marrow-derived dendritic cells (BMDCs). ABH activated immature
      BMDCs, inducing up-regulation of surface molecules, such as CD40, CD80 and major
      histocompatibility complex class I antigens, as well as inducing allogeneic T
      cell proliferation and T helper type 1 cell development. However, unlike
      lipopolysaccharide (LPS), ABH did not stimulate the BMDCs to produce
      proinflammatory cytokines, such as interleukin-12 (IL-12) p40, tumour necrosis
      factor-alpha, or IL-1beta. In addition, ABH suppressed LPS-induced DC responses.
      Pretreatment of DCs with ABH markedly reduced the levels of LPS-induced cytokine
      secretion, while only slightly decreasing up-regulation of the surface molecules
      involved in maturation. ABH also had a significant impact on peptidoglycan
      induced or CpG oligodeoxynucleotide-induced IL-12p40 production in DCs. The
      inhibition of LPS-induced responses was not associated with a cytotoxic effect of
      ABH nor with an anti-inflammatory effect of IL-10. However, ABH decreased NF
      kappaB-induced reporter gene expression in LPS-stimulated J774.1 cells.
      Interestingly, DCs preincubated with ABH and then stimulated with LPS augmented T
      helper type 1 responses in culture with allogeneic T cells as compared to LPS
      stimulated but non-ABH-pretreated DCs. These observations suggest that ABH
      regulates DC-mediated responses.

PMID- 15720442
TI  - Retroviral Foxp3 gene transfer ameliorates liver granuloma pathology in
      Schistosoma mansoni infected mice.
AB  - Schistosomiasis mansoni, a tropical helminthic disease, is caused by disseminated
      worm eggs that induce CD4(+) T-cell mediated granulomatous inflammation and
      fibrosis. T suppressor cell activity has been proposed as one of the mechanisms
      active in the down-modulation of the murine disease during the chronic stage (16
      20 weeks of the infection). In recent years a new category of the CD4(+) CD25(+)
      T regulatory (Treg) lymphocyte has been identified that maintains immune
      tolerance to self, and also functions in the regulation of parasite-induced
      immunopathology. The Foxp3 gene which encodes the transcription factor Scurfin
      was found to be expressed by and required for the generation of CD4(+) CD25(+) T
      reg. At 8 weeks of the infection Foxp3 gene expression of splenocytes was similar
      to that of naive mice, but increased fourfold by 16 weeks. In contrast,
      granulomatous livers at 8 and 16 weeks showed 10- and 30-fold increases,
      respectively, in gene expression compared with normal liver. The percentage of
      granuloma CD4(+) CD25(+) T cells rose from 12% at 8 weeks to 88% at 16 weeks of
      the infection. Foxp3 expression was 3.5-fold higher in the CD4(+) CD25(+) versus
      the CD4(+) CD25(-) T cells in the 8 week infection granulomas. As a novel
      observation neuropilin-1 membrane expression, a recently identified marker for
      Treg, was correlated with Foxp3 expression in the granuloma CD4(+) CD25(+) but
      not the CD25(-) cells. Co-incubation with polyclonal stimulation of CD4(+)
      CD25(+) splenic cells with CD4(+) CD25(-) cells suppressed proliferation of the
      latter. Retroviral transfer of the Foxp3 gene at the onset of granuloma formation
      enhanced fourfold Foxp3 expression in the granuloma CD4(+) CD25(+) T cells and
      strongly suppressed full granuloma development. Gene transfer also significantly
      enhanced transforming growth factor-beta, interferon-gamma and interleukin-4 but
      not interleukin-10 expression. It is concluded, that CD4(+) CD25(+), Foxp3(+)
      Treg cells also regulate schistosome egg-induced immunopathology.

PMID- 15720443
TI  - Lupus autoantibodies to native DNA preferentially bind DNA presented on PolIV.
AB  - While immunoglobulin G (IgG) antibodies to double-stranded (ds)DNA are
      serological markers of systemic lupus erythematosus (SLE), not all antibodies to
      DNA (anti-DNA) are able to cause tissue damage to a similar extent. It has been
      proposed that anti-DNA-induced renal damage could be linked to differences in the
      fine specificity of the antibodies. In an attempt to gain insight into their fine
      binding properties, we investigated the cross-reactivity of two human lupus
      monoclonal IgG anti-dsDNA (B3 and RH14) to a recently described Escherichia coli
      PolIV (a DNA polymerase). These autoantibodies possess distinct pathogenic
      properties in severe combined immunodeficient (SCID) mice. Although both
      antibodies cause proteinuria, only RH14 induces early histological features of
      lupus nephritis. Both RH14 and B3 bound PolIV; however, they exhibited a marked
      difference in their reactivity to the PolIV-dsDNA complex. Alhough RH14 exhibited
      significant activity to the complex, the binding of B3 to PolIV complexed with
      dsDNA was almost abolished. Furthermore, there was a significant difference in
      the way the lupus sera recognized naked dsDNA and that presented on PolIV.
      Although 67% of lupus sera bound naked dsDNA, approximately 90% of these sera
      (93% calf thymus DNA; 90% synthetic oligonucleotide) reacted to the complex when
      dsDNA was presented on PolIV. Thus, the IgG anti-dsDNA likely to exist in lupus
      patients may be distinguished into those that recognize dsDNA in the context of
      PolIV and those which do not. This difference in binding ability may help to
      distinguish those dsDNA antibodies that are more pathogenic.

PMID- 15720446
TI  - Right and left ventricular activation sequence in patients with heart failure and
      right bundle branch block: a detailed analysis using three-dimensional non
      fluoroscopic electroanatomic mapping system.
AB  - Three-dimensional mapping in RBBB and heart failure. INTRODUCTION: Recently,
      right bundle branch block (RBBB) was proved to be an important predictor of
      mortality in heart failure (HF) patients as much as left bundle branch block
      (LBBB). We characterized endocardial right ventricular (RV) and left ventricular
      (LV) activation sequence in HF patients with RBBB using a three-dimensional non
      fluoroscopic electroanatomic contact mapping system (3D-Map) in order to provide
      the electrophysiological background to understand whether these patients can
      benefit from cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Using
      3D-Map, RV and LV activation sequences were studied in 100 consecutive HF
      patients. Six of these patients presented with RBBB QRS morphology. The maps of
      these patients were analyzed and compared post hoc with those of the other 94 HF
      patients presenting with LBBB. Clinical and hemodynamic profile was significantly
      worse in RBBB group compared to LBBB. Patients with RBBB showed significantly
      longer time to RV breakthrough (P<0.001), longer activation times of RV anterior
      and lateral regions (P<0.001), and longer total RV endocardial activation time
      (P<0.02) compared to patients with LBBB. Time to LV breakthrough was
      significantly shorter in patients with RBBB (P<0.001), while total and regional
      LV endocardial activation times were not significantly different between the two
      groups. CONCLUSIONS: Degree of LV activation delay is similar between HF patients
      with LBBB and RBBB. Moreover, patients with RBBB have larger right-sided
      conduction delay compared to patients with LBBB. The assessment of these
      electrical abnormalities is important to understand the rationale for delivering
      CRT in HF patients with RBBB.

PMID- 15720444
TI  - Exposure to mercuric chloride during the induction phase and after the onset of
      collagen-induced arthritis enhances immune/autoimmune responses and exacerbates
      the disease in DBA/1 mice.
AB  - In susceptible mice, mercuric chloride induces a systemic autoimmune response
      that is characterized by elevated serum levels of immunoglobulin G1 (IgG1) and
      immunoglobulin E (IgE), production of anti-nucleolar antibodies (ANolAs) and the
      formation of renal IgG deposits. We have previously shown that mercury can also
      enhance immune/autoimmune responses in mouse strains genetically prone to develop
      spontaneous autoimmune disease. Here, we investigated whether mercury can enhance
      the severity of murine collagen-induced arthritis (CIA), an inducible (acquired)
      autoimmune disease that cannot be induced by mercury itself. While mercury
      administered prior to the induction phase of CIA exerted little, if any,
      influence, administration of mercury during the induction phase and following
      onset aggravated the symptoms of this disease and increased the serum levels of
      IgE and IgG2a antibodies directed against collagen type II (CII). Furthermore,
      while animals injected with mercury alone exhibited a significant decrease in the
      ratio of the levels of interferon-gamma (IFN-gamma) to interleukin-4 (IL-4) mRNA
      in their spleens, this ratio was increased in mice with CIA, with or without
      administration of mercury. Finally, the production of anti-nuclear antibodies, a
      hallmark of autoimmunity in response to mercury, was observed in all mice with
      CIA treated with this heavy metal. Our findings suggest that exposure to mercury
      during the development of CIA may influence immunological factors in such a way
      as to synergistically promote disease development.

PMID- 15720448
TI  - Response to pharmacological challenge of dissociated pulmonary vein rhythm.
AB  - Dissociated pulmonary vein rhythm. INTRODUCTION: Characterization of the
      electrophysiologic behavior of the pulmonary vein (PV) triggers initiating atrial
      fibrillation (AF) is still lacking. We conducted the current study to evaluate
      the behavior of the dissociated PV rhythm (PVD) observed after electrical
      disconnection from the left atrium of the PV responsible for initiation of AF.
      METHODS AND RESULTS: Four hundred and seven consecutive patients (102 women; mean
      age 55+/-11 years) presented for ablation of symptomatic AF to our laboratory.
      After isolation, sustained dissociated rhythm (>10 minutes) was documented in
      2.1% (34 of 1,568 PVs) of the PVs (initiating AF prior to isolation). Adenosine
      (18 mg IV bolus), verapamil (10 mg IV bolus), phenylephrine (200 mcg bolus
      followed by infusion at 100 mcg/hour), and isoproterenol (infusion rate of 15
      mcg/hour) were administered in these patients. The cycle length of the PV rhythm
      before and after the administration of drugs was measured. Adenosine prolonged
      the sinus node (SN) cycle length (from 750+/-105 to 1,900+/-200 ms; P<0.05) and
      suppressed the PVD. Isoproterenol shortened both the SN (from 750+/-105 to 420+/
      150 ms; P<0.05) and the PVD (from 2,225+/-300 to 800+/-190 ms; P<0.05) cycle
      length. A similar response to adenosine and isoproterenol of the PV firing was
      observed prior to isolating the arrhythmogenic PV. Phenylephrine prolonged the
      cycle length of both the SN (from 740+/-115 to 960+/-90 ms; P<0.05) and the PV
      rhythm (from 2,200+/-300 to 2,355+/-280 ms; P=0.87). Verapamil did not cause a
      significant change either in the SN or in the PVD cycle length. CONCLUSION: Our
      data suggest that the PVD within isolated PV responsible for initiating AF
      exhibits a response to pharmacologic agents similar to the SN cells.

PMID- 15720450
TI  - Mahaim fibers: new electrophysiologic insights into an unusual variant.

PMID- 15720449
TI  - Short atrioventricular Mahaim fibers: observations on their clinical,
      electrocardiographic, and electrophysiologic profile.
AB  - Short A-V manheim fiber. INTRODUCTION: A short atrioventricular decrementally
      conducting accessory pathway is an uncommon variant of preexcitation. Available
      data from small series suggest that their decremental properties might not be
      caused by A-V nodal-like tissue. METHODS: We compared clinical,
      electrocardiographic and electrophysiologic parameters in two groups of patients:
      8 patients with a short A-V Mahaim pathway (Group A), and 33 patients with
      atriofascicular pathways (Group B). Radiofrequency catheter ablation was carried
      out guided by activation mapping at the annulus in Group A patients and targeting
      the "M" potential in Group B patients. RESULTS: After ablation of all associated
      rapidly conducting bypass tracts, 7 of the 8 Group A patients showed clear
      preexcitation. In only 1 of 8 patients the short A-V Mahaim fiber was actively
      engaged in a reentrant tachycardia circuit. During radiofrequency catheter
      ablation an automatic rhythm occurred in 4 of 8 patients. Intravenous adenosine
      caused conduction a block in the Mahaim fiber in 3 of the 5 patients tested. In
      group B, no patient showed clear preexcitation (P<00001) while 72% had a minimal
      preexcitation pattern. Twenty-nine of the 33 patients had a circus movement
      tachycardia with AV conduction over the atriofascicular fiber. During
      radiofrequency catheter ablation 30 of 33 patients showed accessory pathway
      automaticity. Adenosine caused transient block at the atriofascicular pathway in
      11 (92%) of the 12 patients tested. CONCLUSIONS: While short decrementally
      conducting right-sided accessory pathways show a typical ECG pattern different
      from atriofascicular pathways, their electrophysiologic properties do not seem to
      be uniform. Those pathways can be successfully interrupted by catheter ablation.

PMID- 15720451
TI  - Electrophysiological and histopathological characteristics of progressive
      atrioventricular block accompanied by familial dilated cardiomyopathy caused by a
      novel mutation of lamin A/C gene.
AB  - Conduction defect caused by lamin A/C gene mutation. INTRODUCTION: Mutations of
      lamin A/C gene (LMNA) cause dilated cardiomyopathy (DCM) with atrioventricular
      (AV) conduction defect, although the electrophysiological and histological
      profiles are not fully understood. METHODS AND RESULTS: We analyzed a large
      Japanese family (21 affected and 203 unaffected members) of DCM with AV block.
      The responsible LMNA mutation of IVS3-10A>G was novel and caused an aberrant
      splicing. The first clinical manifestation was low-grade AV block or atrial
      fibrillation (AF), which developed in affected members aged >or=30 years. We
      observed that the AV block progressed to third-degree within several years. The
      electrophysiological study of the four affected members revealed an impairment of
      intra-AV nodal conduction. Because of advanced AV block, pacemakers were
      implanted in 14 out of 21 affected members at the mean age of 44 years. Three
      affected members died suddenly and two affected members died of heart failure
      and/or ventricular tachycardia (VT) even after the pacemaker implantation.
      Postmortem examination showed conspicuous fibrofatty degeneration of the AV node.
      Endomyocardial biopsies showed remarkably deformed nuclei and substantial
      glycogen deposits in the subsarcolemma. CONCLUSION: The clinical phenotype in
      this family was characterized by (1) the first manifestation of the prolonged PQ
      interval or AF in adolescence, (2) progressive intra-AV nodal block to the third
      degree in several years, and (3) progressive heart failure after pacemaker
      implantation. Histological study revealed preferential degeneration at the AV
      node area and novel cellular damages in the working myocardium.

PMID- 15720452
TI  - Topographic variability of the esophageal left atrial relation influencing
      ablation lines in patients with atrial fibrillation.
AB  - Topography of the esophagus in atrial fibrillation ablation. INTRODUCTION: The
      close anatomic relationship of the posterior wall of the left atrium (LA) and the
      thermosensitive esophagus creates a potential hazard in catheter ablation
      procedures. METHODS AND RESULTS: In 30 patients (pts) with atrial fibrillation
      (AF) undergoing catheter ablation, we prospectively studied the course and
      contact of the esophagus in relation to LA and the topographic proximity to
      ablation lines encircling the right-sided and left-sided pulmonary veins (PV) as
      well as to the posterior line connecting the encircling lines using the
      electromagnetic mapping system for reconstruction of LA and for tagging of the
      esophagus. This new technique of anatomic tagging of the esophagus was validated
      against the CT scan as a standard imaging procedure. The esophageal course was
      highly variable, extending from courses in direct vicinity to the left- or right
      sided PV as well as in the midportion of the posterior LA. In order to avoid
      energy application in direct proximity to the esophagus, adjustments of the left
      and right PV encircling lines were necessary in 14/30 pts (47%) and 3/30 (10%).
      In 30 pts (100%), the mid- to inferior areas of the posterior LA revealed contact
      with the esophagus. Therefore, posterior and inferior linear ablation lines were
      abandoned and shifted to superior in 29 pts (97%). CONCLUSIONS: Anatomic tagging
      of esophagus revealed a highly variable proximity to different areas of the
      posterior LA suggesting individual adjustment of encircling and linear ablation
      lines in AF ablation procedures to avoid the life threatening complication of
      esophagus perforation.

PMID- 15720453
TI  - Numerical simulation of paced electrogram fractionation: relating clinical
      observations to changes in fibrosis and action potential duration.
AB  - Simulating paced electrogram fractionation. INTRODUCTION: Paced electrogram
      fractionation analysis (PEFA) may identify a re-entrant substrate in patients at
      risk of ventricular fibrillation (VF) by detecting prolonged, fractionated
      ventricular electrograms ("fractionation") in response to premature extrastimuli.
      Numerical simulations of action potential (AP) propagation through human
      myocardium following such premature stimulation were performed to study the
      relationship between electrogram fractionation, fibrosis, and changes in AP
      currents. METHODS AND RESULTS: Activation in a resistive monodomain 2 cm2 sheet
      of myocardium containing nonconducting fibrous tissue was modeled using standard
      numerical methods for solutions of partial differential equations using the
      Priebe-Beukelmann (PB) AP equations. Myocardial fibrosis significantly influenced
      electrogram morphology. High densities of closely spaced fibrous septa caused
      functional block and altered propagation paths at short coupling intervals, and
      produced large increases in electrogram duration similar to those associated with
      increased risk of VF in clinical studies. Prolongation of the cardiac AP using
      the heart failure variant of the PB model further increased the amount of
      fractionation and thereby replicated clinical recordings more closely than did
      fibrosis alone. Increasing AP dispersion by a variable reduction in the potassium
      current I(Kr) simulated results seen in patients with the long QT syndrome with
      an abrupt increase in electrogram duration, while a uniform reduction in I(Kr)
      alone did not result in fractionated electrograms. In contrast, increases in
      cytosolic Ca2+ and Ca2+ buffering by troponin to simulate HCM had little effect
      on fractionation. CONCLUSIONS: These results relate the effects of fibrosis, AP
      abnormalities, and dispersion of AP duration to the characteristic electrograms
      recorded in patients at risk of sudden death.

PMID- 15720454
TI  - Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in
      catecholaminergic polymorphic ventricular tachycardia patients with RyR2
      mutations.
AB  - Calcium channel antagonism in RyR2 defects. INTRODUCTION: Recently, gain-of
      function mutations of cardiac ryanodine receptor RyR2 gene have been identified
      as a cause of familial or catecholaminergic polymorphic ventricular tachycardia.
      We examined the influence of the calcium channel blockers, verapamil and
      magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2
      mutations. METHODS AND RESULTS: Six molecularly defined catecholaminergic
      polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on
      beta-adrenergic blocker therapy, underwent exercise stress test four times: at
      baseline, after verapamil and magnesium sulphate infusions, and finally, without
      interventions. The number of isolated and successive premature ventricular
      complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at
      baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature
      ventricular complexes appeared later and at higher heart rate during verapamil
      than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit
      the arrhythmias. Results in the fourth exercise stress test without interventions
      were similar to those in the first baseline study. CONCLUSIONS: This study
      provides the first in vivo demonstration that a calcium channel antagonist,
      verapamil, can suppress premature ventricular complexes and nonsustained
      ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia
      caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium
      antagonists might have therapeutic value.

PMID- 15720455
TI  - Mechanism of propensity to atrial fibrillation in patients undergoing isthmus
      ablation for typical atrial flutter.
AB  - Mechanism of propensity to atrial fibrillation. BACKGROUND: Patients undergoing
      isthmus ablation for atrial flutter (AFL) may reveal postablation atrial
      fibrillation (AF). The electrophysiological mechanism is unclear. In patients
      with idiopathic AF, enhanced spatial dispersion of right atrial refractoriness
      was the substrate for the initiation of AF. We hypothesize that dispersion of
      right atrial refractoriness in patients undergoing AFL ablation is the major
      cause of postablation AF. METHODS: Consecutive patients (n=42) undergoing isthmus
      ablation for typical AFL were included. Twelve right atrial unipolar electrograms
      were recorded. Inducibility of AF was assessed by a pacing protocol, starting
      with one extrastimulus, followed by more aggressive pacing until AF was induced.
      Mean fibrillatory intervals were used to assess local refractoriness of each
      recording site. Spatial dispersion of right atrial refractoriness was calculated
      as the coefficient of dispersion (CD-value: standard deviation of the mean of all
      local mean fibrillatory intervals as a percentage of the overall mean
      fibrillatory interval). A CD-value of 3.0 or less was defined as normal, whereas
      CD-value greater than 3.0 was considered enhanced dispersion. PES and
      refractoriness analysis were followed by isthmus ablation. RESULTS: Of the 42
      patients, 29 had CD-value of 3.0 or less. In these 29 patients, AF was induced
      with 1 extrastimulus in only 1 patient, with 2 extrastimuli in 4 patients and
      burst pacing was required to induce AF in 24 of these 29 patients. Prior to the
      procedure, 5 of 29 patients had AF episodes, after ablation 6 of 29 patients. Of
      the 42 patients, 13 had CD-value greater than 3.0, AF was induced with a single
      extrastimulus in 11 patients, with 2 extrastimuli in the remaining 2 patients. Of
      the 13 patients, 11 had AF episodes both before and after ablation (P<0.001).
      CONCLUSION: Enhanced spatial dispersion of right atrial refractoriness may be the
      substrate for propensity to AF in patients with AFL. The substrate was associated
      with enhanced inducibility of atrial fibrillation.

PMID- 15720456
TI  - Characterization of right atrial substrate in patients with supraventricular
      tachyarrhythmias.
AB  - Right atrial substrate of supraventricular tachyarrhythmias. BACKGROUND: Voltage
      mapping has been used to detect diseased myocardium. However, accurate
      determination of the local atrial voltage at the same site, and simultaneous
      recordings from multiple mapping sites were limited. The purpose of this study
      was to investigate the right atrial (RA) substrate properties in patients with
      supraventricular tachyarrhythmias (SVT). METHODS AND RESULTS: Forty patients
      (aged 55+/-20 years) undergoing noncontact mapping and ablation of SVT
      constituted the study population. There were eight patients with atrioventricular
      node reentrant tachycardia (AVNRT), eight patients with focal atrial tachycardia
      (AT), 14 patients with atrial flutter (AFL), and 10 patients with atrial
      fibrillation (AF). The mean peak negative voltage (PNV) was analyzed in virtual
      unipolar electrograms, which were obtained from 256 equally distributed RA
      endocardial sites during sinus rhythm (SR), atrial pacing, and tachycardia. The
      mean PNV of global RA during SR (-1.34+/-0.22 vs. -0.90+/-0.40 vs. -1.00+/-0.36
      vs. -0.85+/-0.35 mV, P=0.04), atrial pacing at cycle lengths of 500 ms (-1.30+/
      0.29 vs. -0.70+/-0.35 vs. -0.76+/-0.25 vs. -0.64+/-0.26 mV, P=0.02), and 300 ms (
      1.54+/-0.47 vs. -0.94+/-0.21 vs. -0.75+/-0.27 vs. -0.57+/-0.22 mV, P<0.01) were
      significantly greater in patients with AVNRT compared to AT, AFL, and AF.
      Furthermore, the mean PNV decreased during atrial pacing with shorter pacing
      cycle length was demonstrated only in patients with AFL and AF. CONCLUSION:
      Negative unipolar voltage analysis of global RA showed different RA substrate
      characteristics during various SVT. The substrate property of activation and
      cycle length-dependent voltage reduction may be related to the development of AFL
      and AF.

PMID- 15720457
TI  - Temporal patterns of ventricular tachyarrhythmia recurrences follow a Weibull
      distribution.
AB  - Temporal patterns of ventricular tachyarrhythmias. INTRODUCTION: The objective of
      this study was to test whether the temporal patterns of ventricular
      tachyarrhythmia recurrences in patients with implantable cardioverter
      defibrillator (ICD) follow a random or a clustered distribution. METHODS: Data
      analysis was conducted using the Medtronic (Minneapolis, MN) Gem DR database of
      521 ICD patients. Patients with >or=3 sustained ventricular tachyarrhythmia
      detections that resulted in shock or antitachycardia pacing therapies were
      studied. The times between consecutively treated ICD detections for each patient
      were compared to an exponential model of random recurrences and a Weibull model
      for clustered recurrences. RESULTS: Seventy-one patients had >or=3VT episodes
      during follow-up of 131+/-86 days. A total of 2347 VT episodes were recorded
      (33+/-65 episodes/patient, median 10 episodes/patient). Patient age was 66+/-13
      years, 78% male, 83% coronary artery disease, ejection fraction 31+/-11%, and 63%
      were taking antiarrhythmic drugs. By the Kolmogorov-Smirnov goodness-of-fit test,
      38 of 71 patients (53.5%) showed that the pattern of detections differed from an
      exponential model (P<0.01 for each patient and the proportion of patients was
      similar to chance at P=0.65). In contrast, only 11 out of 71 patients (15.5%)
      showed that the pattern differed from the Weibull model (P<0.01 for each
      patient). The proportion of patients fitting the Weibull model was significantly
      greater than chance and was greater that the proportion fitting the exponential
      model (both P<0.001). The time interval between consecutive detections was less
      than 1 hour for 78% of all 2347 detections. The proportion of all 521 patients
      with >or=2, >or=3, >or= 4, >or=6, >or=8, and >or=10 ICD detections in a 24-hour
      period was 10.5%, 9.5%, 8.1%, 7.0%, 6.3%, and 5.2%, respectively. CONCLUSION: In
      most patients with >or=3 ICD detections, the recurrence pattern of treated
      ventricular tachyarrhythmia detections are clustered and can be described by a
      Weibull distribution. The proportion of patients with multiple detections in a 24
      hour period declines in a linear fashion as the number of events in 24 hours
      increases from 2 to 10 events.

PMID- 15720458
TI  - Dissociation of membrane potential and intracellular calcium during ventricular
      fibrillation.
AB  - Membrane potential and intracellular calcium during VF. INTRODUCTION: The cardiac
      action potential (AP) and the intracellular Ca transient (CaT) are closely
      associated under normal physiological conditions, but not during ventricular
      fibrillation (VF). The purpose of this study was to determine whether this
      dissociation is directly related to the fast activation rate during VF. METHODS
      AND RESULTS: We optically mapped AP and CaT simultaneously in nine isolated
      rabbit hearts. Pinacidil, a K(ATP) channel opener, was used to shorten the action
      potential duration (APD) in order to capture tissue at fast pacing rates or to
      induce ventricular tachycardia (VT) comparable to VF activation rates. Mutual
      information (MI) was used to calculate the degree of AP and CaT coupling.
      Pinacidil (40 microM) infusion significantly shortened APD. The CL of VF without
      pinacidil averaged 77+/-13 ms, whereas the shortest CL achieved during VT under
      pinacidil infusion was 76 ms. MIs during fast pacing (1.13+/-0.15 bits) and fast
      VT (0.88+/-0.18 bits) were higher than those during baseline VF (0.39+/-0.11
      bits), VF with pinacidil infusion (0.21+/-0.07 bits) and VF after pinacidil
      washout (0.36+/-0.15 bits). MIs during fast pacing or fast VT were higher than
      that of VFs at comparable dominant frequencies. CONCLUSIONS: CaT is closely
      associated with the AP during fast pacing and fast VT, but not during VF. The
      reduced MI during VF is not secondary to the fast rate of activation.

PMID- 15720459
TI  - Rate-dependent block in the sinus venosa of the swine heart during transverse
      right atrial activation: correlation between electrophysiologic and anatomic
      findings.
AB  - Rate-dependent block in the sinus venosa. INTRODUCTION: Whether the crista
      terminalis or the sinus venosa result in rate-dependent block during transverse
      activation of the right atrial activation remains unknown. In the present study,
      right atrial activation at different cycle lengths was studied in the swine heart
      using high-resolution noncontact mapping (Endocardial Solutions). The location of
      the block was tagged and correlated with postmortem anatomical findings. METHODS
      AND RESULTS: Eight pigs were studied using noncontact mapping to obtain right
      atrial geometry and detailed sequence of activation using noncontact endocardial
      mapping. During sinus rhythm, activation proceeded uninterrupted craniocaudally
      along the sinus venosa and crista terminalis with similar conduction velocities
      (1.08+/-0.17 and 1.17+/-0.14 m/sec, respectively). Proximal coronary sinus
      stimulation was used to create transverse activation of the posterior right
      atrial wall. A rate-dependent decrease in conduction velocity occurred in the
      sinus venosa region (0.93+/-0.21, 0.82+/-0.14, and 0.52+/-0.09 m/sec at 500, 400,
      and 300 ms, respectively; P<0.05). The line of block verified by isopotential
      mapping and double potentials was obtained at cycle lengths of 240+/-30 ms. This
      line of the block was tagged with radiofrequency current lesions. Postmortem, all
      lesions were located in the sinus venosa region, 9.8+/-4.1 mm from the
      posteromedial edge of the crista terminalis. This region showed abrupt changes in
      muscle fiber thickness and orientation as well as in collagen content.
      CONCLUSIONS: The sinus venosa and not the crista terminalis results in a rate
      dependent line of block during transverse right atrial activation. The
      morphologic characteristics of the sinus venosa appear to facilitate block in
      this region.

PMID- 15720461
TI  - Defibrillation depends on conductivity fluctuations and the degree of
      disorganization in reentry patterns.
AB  - Defibrillation depends on conductivity and disorganization. INTRODUCTION: Cardiac
      fibrillation is the deterioration of the heart's normally well-organized activity
      into one or more meandering spiral waves, which subsequently break up into many
      meandering wave fronts. Delivery of an electric shock (defibrillation) is the
      only effective way of restoring the normal rhythm. This study focuses on
      examining whether higher degrees of disorganization requires higher shock
      strengths to defibrillate and whether microscopic conductivity fluctuations favor
      shock success. METHODS AND RESULTS: We developed a three-dimensional computer
      bidomain model of a block of cardiac tissue with straight fibers immersed in a
      conductive bath. The membrane behavior was described by the Courtemanche human
      atrial action potential model incorporating electroporation and an acetylcholine-
      (ACh) dependent potassium current. Intracellular conductivities were varied
      stochastically around nominal values with variations of up to 50%. A single rotor
      reentry was initiated and, by adjusting the spatial ACh variation, the level of
      organization could be controlled. The single rotor could be stabilized or spiral
      wave breakup could be provoked leading to fibrillatory-like activity. For each
      level of organization, multiple shock timings and strengths were applied to
      compute the probability of shock success as a function of shock strength.
      CONCLUSIONS: Our results suggest that the level of the small-scale conductivity
      fluctuations is a very important factor in defibrillation. A higher variation
      significantly lowers the required shock strength. Further, we demonstrated that
      success also heavily depends on the level of organization of the fibrillatory
      episode. In general, higher levels of disorganization require higher shock
      strengths to defibrillate.

PMID- 15720460
TI  - Effects of temporal application parameters on lesion dimensions during
      transvenous catheter cryoablation.
AB  - Lesion dimension of cryoablation. BACKGROUND: Transvenous catheter cryoablation
      is a novel technique for treating cardiac arrhythmias. However, the relative
      importance of temporal application parameters on lesion dimension and clinical
      efficacy has not been studied. METHODS AND RESULTS: We investigated the effects
      of (1) application duration: single 2.5 (2.5x1) versus single 5 versus double 2.5
      (2.5x2) versus double 5 (5x2) minutes, (2) number of freeze-thaw cycles: single
      versus double, and (3) electrode contact area: horizontal versus vertical
      orientation, on the lesion diameter and depth during catheter cryoablation (10F,
      6.5-mm tip-electrode, CryoCor, San Diego) in a thigh muscle preparation. A total
      of 175 lesions (horizontal=90, vertical=85) were created in thigh muscle
      preparations on 10 swine. The lesion diameter and depth were significantly
      greater using 2.5x2 and 5x2 application modes as compared with 2.5x1 applications
      (P<0.05). Horizontal tip-electrode orientation produced larger lesion diameter
      (P<0.05), but not lesion depth as compared with vertical orientation.
      Multivariate analysis demonstrated that both tip-electrode orientation and
      duration of freeze >2.5 minutes were independent predictors for lesion diameter
      (P<0.001). However, only duration of freeze >2.5 minutes was an independent
      predictor for lesion depth (P<0.001). CONCLUSIONS: The dimensions of lesions
      created by catheter cryoablation are affected by mode of cryoablation application
      and electrode orientation. Increasing the duration of application, employing
      multiple freeze-thaw cycles at shorter cycle durations, and orienting the
      catheter to enhance/increase tissue contact can create a larger lesion.

PMID- 15720462
TI  - Spontaneous T wave alternans in a patient with Brugada syndrome--responses to
      intravenous administration of class I antiarrhythmic drug, glucose tolerance
      test, and atrial pacing.
AB  - Spontaneous T wave alternans in Brugada syndrome. A 43-year-old man with an
      episode of syncope showed ECG patterns of coved-type ST elevation in leads V1-V3
      and right bundle branch block pattern. The patient had spontaneous T wave
      alternans at baseline, and T wave alternans diminished with distinct development
      of ST elevation after administration of Na+ channel blocker, and during oral
      glucose load and atrial pacing. Na+ channel mutation may contribute to the
      genesis of his ECG changes.

PMID- 15720464
TI  - A consult for "incessant palpitations": what is the rhythm?

PMID- 15720463
TI  - Multiple pacing lead-induced superior vena cava syndrome: successful treatment by
      balloon angioplasty.
AB  - Pacemaker-induced SVC syndrome. The superior vena cava (SVC) syndrome is an
      uncommon but sometimes serious complication associated with permanently implanted
      pacemakers. The mechanical stress associated with pacemaker wires may lead to
      vessel wall inflammation, fibrosis, thrombus formation, and, ultimately, venous
      stenosis and occlusion. The surgical treatment of pacemaker-related SVC syndrome
      requires thoracotomy and may result in significant morbidity. The long-term
      effects on the pacemaker electrodes, due to compression between the stent and the
      wall of the vein, remain unknown. We describe a case in which balloon venoplasty
      successfully resolved the SVC syndrome. The patient has remained symptom-free and
      with normal pacemaker function for 6 months.

PMID- 15720465
TI  - Supraventricular tachycardia upon termination of atrial flutter: what is the
      mechanism?

PMID- 15720466
TI  - Catheter ablation of atrial fibrillation originating from the non-pulmonary vein
      foci.

PMID- 15720467
TI  - A NavX guided cryoablation of an accessory pathway in a large coronary sinus
      diverticulum.
AB  - J Cardiovasc Electrophysiol, Vol. 16, pp. 1-2, February 2005.

PMID- 15720468
TI  - Arrhythmogenic right ventricular dysplasia: catheter ablation, MRI, and heart
      transplantation.

PMID- 15720469
TI  - Melanotrope cells of Xenopus laevis express multiple types of high-voltage
      activated Ca2+ channels.
AB  - Pituitary melanotrope cells are neuroendocrine signal transducing cells that
      translate physiological stimuli into adaptive hormonal responses. In this
      translation process, Ca2+ channels play essential roles. We have characterised
      which types of Ca2+ current are present in melanotropes of the amphibian Xenopus
      laevis, using whole-cell, voltage-clamp, patch-clamp experiments and specific
      blockers of the various current types. Running an activation current-voltage
      relationship protocol from a holding potential (HP) of -80 mV/or -110 mV, shows
      that Xenopus melanotropes possess only high-voltage activated (HVA) Ca2+
      currents. Steady-state inactivation protocols reveal that no inactivation occurs
      at -80 mV, whereas 30% of the current is inactivated at -30 mV. We determined the
      contribution of individual channel types to the total HVA Ca2+ current, examining
      the effect of each channel blocker at an HP of -80 mV and -30 mV. At -80 mV,
      omega-conotoxin GVIA, omega-agatoxin IVA, nifedipine and SNX-482 inhibit Ca2+
      currents by 21.8 +/- 4.1%, 26.1 +/- 3.1%, 24.2 +/- 2.4% and 17.9 +/- 4.7%,
      respectively. At -30 mV, omega-conotoxin GVIA, nifedipine and omega-agatoxin IVA
      inhibit Ca2+ currents by 33.8 +/- 3.0, 24.2 +/- 2.6 and 16.0 +/- 2.8%,
      respectively, demonstrating that these blockers substantially inhibit part of the
      Ca2+ current, independently from the HP. We have previously demonstrated that
      omega-conotoxin GVIA can block Ca2+ oscillations and steps. We now show that
      nifedipine and omega-agatoxin IVA do not affect the intracellular Ca2+ dynamics,
      whereas SNX-482 reduces the Ca2+ step amplitude. We conclude that Xenopus
      melanotrope cells express all four major types of HVA Ca2+ channel, as well as
      the resulting currents, but no low-voltage activated channels. The results
      provide the basis for future studies on the complex regulation of channel
      mediated Ca2+ influxes into this neuroendocrine cell type as a function of its
      role in the animal's adaptation to external challenges.

PMID- 15720470
TI  - Introduction of a high-energy diet acutely up-regulates hypothalamic cocaine and
      amphetamine-regulated transcript, Mc4R and brown adipose tissue uncoupling
      protein-1 gene expression in male Sprague-Dawley rats.
AB  - Obesity is an escalating problem in Western societies. Susceptibility to weight
      gain within an obesogenic environment is variable. It remains unclear how the
      range of weight gain responses are generated. It is possible that an individual's
      immediate and/or sustained appetite for apparently palatable foods, or metabolic
      adaptations to a new diet could be important. The present study therefore
      examined the short- to medium-term effects of a high-energy (HE) diet on
      bodyweight, food intake, and energy balance-related signalling systems. Sprague
      Dawley rats were fed either chow or an HE diet for 12 h, 24 h, 48 h or 14 days.
      Blood hormones and metabolites were assayed, and expression of uncoupling protein
      1 (UCP-1) and hypothalamic energy-balance related genes were determined by
      Northern blotting or in situ hybridisation, respectively. Short-term exposure (12
      h, 24 h, 48 h) to the HE diet had no effect on grams of food consumed, but
      caloric intake was increased. Exposure to HE diet for 14 days (medium term)
      established a bodyweight differential of 7.7 g, and animals exhibited a transient
      increase in caloric intake of 5 days duration. Terminal levels of leptin,
      insulin, glucose and non-esterified fatty acids (NEFAs) were all increased in HE
      fed animals. UCP-1 mRNA was elevated in interscapular brown adipose tissue from
      HE-fed rats only at 12 h. Cocaine and amphetamine-regulated transcript (CART) and
      Mc4R gene expression in the hypothalamus were increased after 12 h and 24 h on an
      HE diet, respectively. The rats appear to passively over-consume calories as a
      result of consuming a similar weight of a more energy dense food. This evokes
      physiological responses, which adjust caloric intake over several days.
      Circulating NEFA and insulin concentrations, UCP-1, Mc4R and CART gene expression
      are increased as an immediate consequence of consuming HE diet, and may be
      involved in countering hypercaloric intake. Circulating leptin is increased in
      the HE-fed animals after 48 h, reflecting their increasing adiposity.

PMID- 15720471
TI  - Short day lengths enhance skin immune responses in gonadectomised Siberian
      hamsters.
AB  - In Siberian hamsters and other photoperiodic rodents, exposure to short
      photoperiods simultaneously inhibits gonadal hormone secretion and enhances some
      measures of immune function. The present study tested whether gonadal hormones
      mediate the effects of short days on skin immune function (delayed-type
      hypersensitivity reactions) in male Siberian hamsters. The magnitude of delayed
      type hypersensitivity reactions was greater in hamsters exposed to short days
      relative to those in long days. Comparable effects of photoperiod were obtained
      in castrated hamsters bearing empty or testosterone-filled implants. The data
      suggest that contemporary gonadal hormone secretion is neither necessary, nor
      sufficient to mediate the effects of short photoperiods on skin immune function.

PMID- 15720472
TI  - Norepinephrine release in medial amygdala facilitates activation of the
      hypothalamic-pituitary-adrenal axis in response to acute immobilisation stress.
AB  - Activation of the brain noradrenergic system during stress plays an important
      integrative function in coping and stress adaptation by facilitating transmission
      in many brain regions involved in regulating behavioural and physiological
      components of the stress response. The medial amygdala (MeA) has been implicated
      in modulation of stress-induced activation of the hypothalamic-pituitary-adrenal
      (HPA) axis, and MeA is a target of innervation from brainstem noradrenergic
      neurones. However, it is not known whether, and to what extent, activation of the
      ascending noradrenergic innervation of MeA might modulate stress-induced
      adrenocorticotropic hormone (ACTH) secretion. In the first experiment in this
      study, we measured extracellular norepinephrine (NE) levels in MeA using in vivo
      microdialysis. The concentration of NE in dialysate samples collected in MeA was
      elevated by more than three-fold over baseline in response to acute
      immobilisation stress, providing evidence of a possible modulatory role for NE in
      the MeA during stress. This potential role was then assessed in the second
      experiment by measuring changes in the elevation of plasma ACTH concentration
      induced by acute immobilisation stress immediately following bilateral
      microinjections of alpha1- or beta-adrenergic receptor antagonists directly into
      MeA. Compared to vehicle-injected controls, the alpha1-receptor antagonist
      benoxathian dose-dependently and significantly attenuated the ACTH response to
      acute stress, whereas combined beta1/beta2-receptor blockade in MeA had only a
      modest effect. These results indicate that MeA does play a role in the stress
      response, and support the hypothesis that stress-induced activation of NE release
      in MeA, acting primarily through alpha1 receptors, facilitates activation of the
      HPA axis in response to acute stress.

PMID- 15720473
TI  - Oestrogen receptor beta-immunoreactive neurones in the ovine hypothalamus:
      distribution and colocalisation with gonadotropin-releasing hormone.
AB  - Oestrogen powerfully affects the secretion of gonadotropin-releasing hormone
      (GnRH) from the brain in all species investigated, including sheep. Until
      recently, it was hypothesised that such regulation occurs indirectly because few
      or no GnRH neurones were found to express oestrogen receptor (ER) alpha. The
      discovery of a second oestrogen receptor, ERbeta, and its subsequent localisation
      in numerous GnRH neurones in the rat, led to a reconsideration of this
      hypothesis. However, colocalisation of immunoreactive ERbeta protein in GnRH
      neurones has only been demonstrated in the rat, raising the possibility that such
      putative direct regulation of GnRH neurones by oestrogen may be peculiar to this
      species. We have previously shown that steroid receptors in the sheep brain are
      acutely sensitive to fixation and the full complement of immunoreactive cells can
      only be visualised after antigen retrieval. The aims of this study were therefore
      to map immunocytochemically the distribution of ERbeta neurones in the ewe brain,
      and to determine which proportion of GnRH neurones express ERbeta. Brain sections
      (20 microm) from four ewes killed in anestrus were subjected to high temperature
      antigen retrieval and immunocytochemistry. Numerous ERbeta-immunoreactive cells
      were located throughout the hypothalamus and, following dual-label
      immunocytochemistry, over 50% of the GnRH neurones were found to express
      immunoreactive ERbeta. The functional significance of these ERbeta-expressing
      GnRH neurones in the ovine brain remains to be determined.

PMID- 15720474
TI  - Reduced activity of the noradrenergic system in the paraventricular nucleus at
      the end of pregnancy: implications for stress hyporesponsiveness.
AB  - We investigated whether changes in noradrenaline neurotransmission in the
      hypothalamus could explain the hyporesponsiveness of the hypothalamic-pituitary
      adrenal (HPA) axis in late pregnancy. Noradrenaline release within the
      hypothalamic paraventricular nucleus in response to swim stress, as estimated by
      microdialysis and high-performance liquid chromatography, was lower in 20-day
      pregnant rats compared to virgin rats. Driving a central noradrenergic pathway
      using intravenous cholecystokinin increased adrenocorticotropic hormone (ACTH)
      secretion in virgin rats, but the response was significantly less in 16-day and
      20-day pregnant rats. Thus, the activity of noradrenergic inputs to the
      paraventricular nucleus and the HPA axis is attenuated in late pregnancy. The
      sensitivity of the HPA axis to noradrenaline in pregnancy was investigated by
      intracerebroventricular administration of an alpha1-receptor antagonist,
      benoxathian, before and during exposure to swim stress. In virgin rats,
      benoxathian increased basal and stress-induced ACTH secretion, but in late
      pregnant rats the benoxathian effects were attenuated, indicating reduced
      sensitivity of the HPA axis to noradrenaline neurotransmission and/or the
      inability of the system to become disinhibited at this time. alpha1A
      adrenoreceptor mRNA expression in the parvocellular and magnocellular
      paraventricular nucleus, measured by in situ hybridisation, was decreased in late
      pregnant compared to virgin rats. Additionally, blocking endogenous opioid
      inhibition with naloxone pretreatment restored the ACTH secretory response to
      cholecystokinin in pregnant rats. Thus, in late pregnancy, there is reduced
      noradrenergic input to the paraventricular nucleus and reduced alpha1A-receptor
      expression in the paraventricular nucleus, both of which may contribute to the
      reduced responsiveness of the HPA axis in pregnancy.

PMID- 15720475
TI  - Effects of GABAB receptor modulation on gonadotropin-releasing hormone and beta
      endorphin release, and on catecholaminergic activity in the ventromedial
      hypothalamus-infundibular nucleus region of anoestrous ewes.
AB  - To examine the role of gamma-aminobutyric acid (GABA)B receptor mediating systems
      in the ventromedial hypothalamus-infundibular nucleus region (VMH/NI) of
      anoestrous ewes in controlling gonadotropin-releasing hormone (GnRH) release, the
      extracellular concentrations of GnRH, beta-endorphin, norepinephrine, dopamine, 4
      hydroxy-3-methoxy-glycol and 3,4-dihydroxy-phenylacetic acid were quantified
      during infusion of baclofen or phaclofen (agonist and antagonist of GABAB
      receptors, respectively) in this structure. The stimulation of GABAB receptors
      activates GnRH/luteinising hormone (LH) release, attenuates noradrenergic and
      beta-endorphinergic tone but has no evident effect on the dopaminergic system.
      Blockade of GABAB receptors in this structure increases the extracellular beta
      endorphin concentration but has no significant influence on GnRH release or
      catecholaminergic activity. It is suggested that activation of GnRH/LH release in
      the VMH/NI of anoestrous ewes may result from a decrease of norepinephrine output
      and hence its inhibitory effect on GnRH secretion. Activation of GABAB receptors,
      as well as their blockade, did not change dopaminergic system activity,
      indicating that GABAB does not affect GnRH release indirectly by a GABAB receptor
      mechanism acting on dopaminergic neurones in the VMH/NI. Increased activity of
      the beta-endorphinergic system during blockade of GABAB receptors does not change
      GnRH release, suggesting that beta-endorphin does not play a significant role in
      the control of GnRH secretion in anoestrous ewes.

PMID- 15720476
TI  - Phytoestrogen action in the adult and developing brain.
AB  - Abstract Soy isoflavonoids are plant phytoestrogens available as dietary
      supplements and are increasingly advocated as a natural alternative to oestrogen
      replacement therapy. As weak oestrogen agonists/antagonists with a range of other
      enzymatic activities, the isoflavonoids provide a useful model to investigate the
      actions of endocrine disruptors. Here, the activational and organisational
      effects of these compounds on the brain are reviewed. In spite of their
      preferential affinity for oestrogen receptor (ER)beta in vitro, isoflavonoids act
      in vivo through both ERalpha and ERbeta. Their neurobehavioural actions are
      largely anti-oestrogenic, either antagonising or producing an action in
      opposition to that of oestradiol. Small, physiologically relevant exposure levels
      can alter oestrogen-dependent gene expression in the brain and affect complex
      behaviour in a wide range of species. The implications for these findings in
      humans, and particularly in infants, largely remain uninvestigated but are a
      subject of increasing public interest.

PMID- 15720477
TI  - New nursing roles--implications for nursing management.

PMID- 15720478
TI  - Creating an organizational infrastructure to develop and support new nursing
      roles--a framework for debate.
AB  - AIM: This paper offers for debate a framework that will promote an effective
      organizational infrastructure when developing and supporting new nursing roles.
      The framework identifies key systems that need to work effectively in isolation
      but also clearly integrate to ensure a joined up approach to organizational
      thinking and working. A working example of how the infrastructure could be
      initiated in practice utilizing the concept of developing an Advanced
      Practitioner role is offered. BACKGROUND: The National Health Service has set out
      a modernization agenda to deliver consistent and high quality care to patients.
      However, often underpinning government vision and philosophy is the need for
      trust strategies to make real and operationalize recommendations made. It is
      against this background of government targets and change in the National Health
      Service that new nursing roles are created, which require an effective
      organizational infrastructure if they are to survive, let alone succeed. The
      government seems to be recognizing that lessons could be learned when developing
      new roles in the National Health Service by acknowledging the key themes
      identified from the earlier literature on the development and impact of new roles
      in nursing. KEY ISSUES: In reality, each of the key systems identified as part of
      the framework is very complex, particularly in large organizations. However, the
      framework proposed offers a simplified and user-friendly approach to this complex
      subject. There is no suggestion that organizations do not have the systems in
      place but what is often missing is the underpinning communications to link the
      systems together. Although, this paper relates to nursing roles the framework is
      transferable to all health care practitioners and organizations. CONCLUSION:
      Whilst supporting new roles, the framework presented offers a wider dimension for
      enhancing organizational thinking and working practices. It is open to debate,
      which would be welcomed by the authors, yet provides a challenge to health care
      organizations in assessing how integrated their systems are in meeting its
      business, aspirations and new targets.

PMID- 15720479
TI  - 'Working from the inside': an infrastructure for the continuing development of
      nurses' professional clinical practice.
AB  - AIM: This paper describes how the nursing executive of a tertiary referral
      facility revisited their management structures and responsibilities to create a
      new, sustainable infrastructure that supports research and education at the core
      of nursing practice and not at the periphery. BACKGROUND: Nursing executive and
      senior management groups are charged with the ultimate responsibility of ensuring
      the highest possible quality nursing care within their facility. In the current
      health care climate the aim for best practice conflates with evidence-based
      practice that can be notoriously difficult to achieve due to the many barriers to
      integrating research findings into practice. KEY ISSUES: Research and education
      activities have been established as fundamental to core business under a simple
      evidence-based practice model. CONCLUSION: The value of a synthesis between the
      clinical areas with the nursing education and research division has been
      recognized to better achieve the goal of improved services.

PMID- 15720480
TI  - Care management of Creutzfeldt-Jakob Disease within the United Kingdom.
AB  - The purpose of this article is to review the management of health and social care
      provision for Creutzfeldt-Jakob Disease patients within the United Kingdom. The
      link between the epidemic of bovine spongiform encephalopathy (BSE) in cattle and
      the subsequent emergence of variant Creutzfeldt-Jakob Disease (vCJD) in humans
      during the mid 1990s created new mechanisms for the organization of health and
      social care for Creutzfeldt-Jakob Disease patients. This article draws on the
      experiences of two National Care Co-ordinators appointed to manage the care of
      Creutzfeldt-Jakob Disease patients throughout the United Kingdom, and identifies
      how additional money set aside by the Department of Health (DoH) is spent to
      overcome local difficulties in the timeliness or availability of services. The
      key issues that emerge include the positive benefits associated with care co
      ordination and the difficulties encountered in developing flexible and individual
      care packages within existing health and social organizational structures.

PMID- 15720481
TI  - Patients' preferences for involvement in clinical decision-making within
      secondary care and the factors that influence their preferences.
AB  - The research aimed to identify what involvement patients want in clinical
      decision-making and explore the underlying factors influencing that choice, thus
      identifying aids and barriers to increasing patients' involvement in decision
      making. The study design was inspired by interpretative phenomenology, thus the
      framework for analysis is intended to aid interpretation and comprehension of the
      patients' experiences and understanding through identifying similarities and
      differences in their stories. Data were collected through semi-structured
      interviews of twenty people who were patients in a secondary care milieu at the
      time of interview. Results showed that, 20% of patients chose an active role in
      decision-making and 80% chose a collaborative or a passive role. However what
      people selected on the autonomy preference index was not always reflected in the
      interview. Additionally, the findings suggest that the NHS maintains a
      paternalistic approach. Lack of staff, lack of information and poor continuity of
      care with nursing staff made patients feel disempowered.

PMID- 15720482
TI  - Transformational leadership: a cascading chain reaction.
AB  - Historical influences still permeate contemporary nursing practise. These are
      mirrored in organizational philosophies, transactional and autocratic leadership
      styles and disempowered staff. Whilst there is disparity amongst the theorists'
      definitions of leadership, there is consensus pertaining to the attributes
      necessary to realize effective leadership. Transformational leadership is
      heralded as new criterion for nurse managers, and can be achieved through
      training, education and professional development in key leadership competencies.
      To achieve a chain reaction, charismatic transformational leaders espouse
      intellectual stimulation and individual consideration to empower staff and
      enhance patient care. Nurse managers that develop and foster transformational
      leadership can surmount oppressive traditions and confidently navigate a complex
      and rapidly changing health care environment.

PMID- 15720483
TI  - Leadership style and choice of strategy in conflict management among Israeli
      nurse managers in general hospitals.
AB  - AIMS: To identify conflict mode choices of head nurses in general hospitals and
      examine the relationship between leadership style, choice of strategy in handling
      conflicts and demographic characteristics. BACKGROUND: Nurse managers deal with
      conflicts daily. The choice of conflict management mode is associated with
      managerial effectiveness. The ability to creatively manage conflict situations,
      towards constructive outcomes is becoming a standard requirement. METHODS: Head
      nurses (N = 60) in five general hospitals in central Israel were surveyed, using
      a 3-part questionnaire: The Thomas-Kilmann Conflict Mode Instrument, the Multi
      factor Leadership Questionnaire, Form 5X-Short (MLQ 5X) and demographic data.
      RESULTS: Head nurses perceive themselves significantly more as transformational
      leaders than as transactional leaders. Compromise was found to be the most
      commonly used conflict management strategy. Approximately half of the nurses
      surveyed used only one mode in conflict management. Transformational leadership
      significantly affected the conflict strategy chosen. CONCLUSION: Head nurses tend
      to choose a conflict-handling mode which is concerned a form of a Lose-Lose
      approach. Preparation in conflict management should start from undergraduate
      education.

PMID- 15720484
TI  - Work empowerment as experienced by head nurses.
AB  - BACKGROUND: Head nurses have in the past few decades gained both more power and
      more responsibilities in their job. Their experience of work empowerment is not
      known. AIM: The aim of this study was to describe the verbal, behavioural and
      outcome empowerment experienced by head nurses. METHODS: Data were collected
      using a structured questionnaire, which was sent to 259 head nurses. The data
      were analysed using statistical methods. RESULTS: The results suggest that head
      nurses experience quite strong verbal and behavioural empowerment. They feel less
      confident in terms of outcome empowerment. Various factors, including stress and
      the capacity to handle the head nurse's job, were found to correlate with the
      empowerment experience. CONCLUSION: It seems that head nurses do not have enough
      power to influence the effectiveness of their organization.

PMID- 15720485
TI  - Practice and clinical decision-making autonomy among Hellenic critical care
      nurses.
AB  - BACKGROUND: Nursing autonomy has been associated with better patient-outcomes;
      therefore, it is a priority for critical care nursing management. Low authority
      has been a persistent complaint of Hellenic intensive care unit nurses; however,
      issues of nursing autonomy have not been previously addressed empirically in
      Hellas. PURPOSE: To investigate: (1) the perceived contribution to clinical
      decision-making, (2) the degree of autonomy in technical tasks, and (3) factors
      related to practice autonomy in critical care nurses in Hellas. Additionally,
      because of the lack of sufficient tools, this study also aimed to construct and
      to validate a new tool for assessing practice and clinical decision-making
      autonomy among Hellenic intensive care unit nurses. MATERIALS AND METHODS: A
      Hellenic intensive care nursing autonomy scale, focused on technical aspects of
      care, was developed through literature review, a panel of experts and a pilot
      study in a random sample of 120 respondents. Items were refined by factor
      analysis, which revealed three major conceptual categories of autonomy: (1) basic
      technical, (2) advanced technical, and (3) clinical decision. Hellenic intensive
      care nursing autonomy (Likert 4, range: 38-152), was distributed to all nurses
      employed in intensive care units in Hellas (n = 807; attrition: 27%).
      Comparisons, correlation and multivariate regression were employed. RESULTS: The
      Hellenic intensive care nursing autonomy scale exhibited appropriate reliability
      (Cronbach's alpha = 0.86) and validity properties. Autonomy scores were moderate
      (mean: 105.24 +/- 9.58). Highest autonomy was attributed to basic technical
      tasks, followed by advanced technical tasks and decision-making. Male gender and
      higher education were predictors of higher overall, advanced technical and
      decision-making autonomy (P = 0.01). Bachelor degree graduates scored higher in
      decisional autonomy (P = 0.03). Intensive care unit experience and type of
      intensive care unit were also important determinants of decisional autonomy (P =
      0.02). CONCLUSIONS: The results revealed moderate autonomy in technical tasks and
      low decisional autonomy among Hellenic intensive care unit nurses. Factors
      related to the educational preparation of nurses, gender issues and institutional
      characteristics might hinder intensive care unit nurses' autonomy in Hellas.

PMID- 15720486
TI  - Health care assistants: the views and perceptions of course co-ordinators in the
      Republic of Ireland.
AB  - AIM: A research study was undertaken in Ireland to evaluate a pilot Healthcare
      Support course. One aim of the study was to obtain the views and perceptions of
      the course coordinators on a range of issues relating to the training programme.
      BACKGROUND: From the beginning of formal UK health care, there have always been
      unqualified or untrained assistants working within hospital and community
      settings. The provision of relevant training for these staff members has a number
      of benefits not just to registered nurses but also to patients, managers and
      health care assistants (HCAs) themselves. METHODS: Semistructured interviews were
      undertaken with course coordinators in 14 pilot sites across Ireland. RESULTS:
      The coordinators maintained that the course was too short but acknowledged that
      this was a pilot programme. The course structure was perceived to be appropriate
      and with the content relevant to the skills and knowledge required by HCAs.
      Selection criteria were varied across the pilot sites which led to some
      difficulties for coordinators. CONCLUSIONS: Overall, coordinators felt that the
      trainees on the programme were committed and motivated and that the course
      increased their knowledge and skills and was a rewarding experience.

PMID- 15720487
TI  - Israeli men in nursing: social and personal motives.
AB  - AIM: This paper intends to explore what leads Israeli men to choose nursing as
      their profession. BACKGROUND: In the early years of nursing education in Israel,
      like in other western societies, men were excluded from the profession. Shortage
      in nursing personnel and urgent needs led to recruitment of men into the
      profession for a short period of time. Only since the early 1990s the nursing
      profession is experiencing a gradual but steady influx of men. Yet, nursing is
      generally perceived as women's work, and men have to cope with the stereotypes
      attributed to them as a prominent minority in a profession primarily occupied by
      women. Currently, no study had examined who are the Israeli men who are willing
      to enter the profession and why. METHODS: A 52-item questionnaire was distributed
      among all registered female and male nurses in three general and three
      psychiatric hospitals during 1997-98. The questionnaire covered sociodemographic
      characteristics, exposure to the profession and reasons for choosing the
      profession. The response rate of 74% included 123 male and 137 female registered
      nurses. CONCLUSIONS: Early exposure to the profession and the fact that the
      majority of male nurses belong to ethnic minorities and recent immigrants to the
      Israeli society were the most prominent factors in the selection of the nursing
      profession by these men. Surprisingly, economic considerations did not constitute
      a compelling motive in this population.

PMID- 15720488
TI  - Conceptions of gender--a study of female and male head nurses' statements.
AB  - BACKGROUND: Gender can be seen as a construction in which history, culture and
      social relation are central. Thus, the construction remains strong can be
      explained by the fact that the existing conceptions about gender are continually
      passed on. It is not known how conceptions about gender in the context of Swedish
      health care are expressed by head nurses or what significance the conceptions
      have for their leadership. AIM: To study head nurses' statements about their
      conceptions of gender and what significance these conceptions have in carrying
      out their work. METHODS: Thematic interviews were held with 36 head nurses, and
      the contents of the transcribed interviews were analysed. RESULTS: The results
      showed conceptions about men's direct and women's roundabout ways of
      communicating. Statements were also made concerning how men are oriented towards
      technical matters and women towards relationships, and how men are expected to
      show what they can do to a greater extent than women. These conceptions have an
      effect on head nurses in their work, as they are expected to live up to them. As
      we wished to obtain variation in the respondents' statements about gender, we
      conducted an interview study. Hence, the transferability of the findings is a
      question of conceptualization, and the conceptions we recorded cannot be seen as
      representative for all head nurses. The results imply, however, that greater
      awareness about conceptions of gender may promote greater equality in women's and
      men's careers and allow greater freedom to head nurses to do what they themselves
      feel they should do instead of what they are expected to do.

PMID- 15720491
TI  - Mental health awareness: balancing the image.

PMID- 15720492
TI  - Staff attitudes towards aggression in health care: a review of the literature.
AB  - The aim of this literature review was to explore the attitudes of health care
      workers towards inpatient aggression and to analyse the extent to which
      attitudes, as defined from a theoretical point of view, were addressed in the
      selected studies. Databases from 1980 up to the present were searched, and a
      content analysis was done on the items of the selected studies. The concepts
      'cognition' and 'attitude' from the framework of 'The Theory of Reasoned Action'
      served as categories. The self-report questionnaire was the most common
      instrument used and three instruments specifically designed to measure attitudes
      were found. These instruments lacked profound validity testing. From a total of
      74 items, two thirds focussed on cognitions and only a quarter really addressed
      attitudes towards aggression. Research was particularly concerned with the
      cognitions that nurses had about aggression, and attitudes were studied only to a
      limited extent. Researchers used different instruments, which makes it difficult
      to compare results across settings.

PMID- 15720493
TI  - Community psychiatric nursing: focus on effectiveness.
AB  - The focus for provision of mental health services is now the community in most
      developed countries. Different ways of organizing community mental health
      services are evident in the literature. Community psychiatric nurses (CPNs) have
      a key role to play in these services but the literature indicates that the CPN
      role varies from area to area within different models of service provision. This
      paper presents the findings of a study in which 13 service users and 15 CPNs in
      five focus groups discussed the effectiveness of mental health service. Selected
      staff and service users were chosen from a representative range of community
      mental health services across Northern Ireland. Service users expressed concern
      at the variety of CPN and other professional roles within multidisciplinary teams
      and some CPNs expressed dissatisfaction with their role and with role boundaries
      within teams. These findings suggest that further work is needed within community
      mental health services to ensure the role of the CPN remains effective and
      develops to meet the needs of service users.

PMID- 15720494
TI  - Trust as a foundation for the therapeutic intervention for patients with
      borderline personality disorder.
AB  - A qualitative, exploratory, descriptive and contextual study using an
      'interpretive descriptive approach' was undertaken in order to develop a practice
      level model for the facilitation of mental health of patients diagnosed as having
      Borderline Personality Disorder by the community psychiatric nurse. The context
      of the study was the in the Psychiatric Community Services in the greater
      Johannesburg region, South Africa. Individual and focus group interviews were
      conducted with patients and mental health clinicians representing the
      multidisciplinary team with experience in managing the condition, either in a
      personal capacity or as professional mental health practitioners. Themes
      extrapolated from the transcribed interviews were further explored and a practice
      based theory was constructed. This article reports on the first theme 'Trust',
      the concept identified by both patients and clinicians as crucial for the
      establishment and maintenance of the therapeutic relationship that forms the
      vehicle for care of patients with this disorder in psychiatric mental health
      care.

PMID- 15720495
TI  - A system of patient classification in long-term psychiatric inpatients: Resource
      Utilization Groups T-18 (RUG T-18).
AB  - This paper shows the application of a 'case mix' system (Resources Utilization
      Groups T18 or RUG-T18) to a Spanish long-term inpatient psychiatric sample.
      OBJECTIVE: To examine the capacity of RUG-T18 to predict patient resource use
      (spent time of care) in a long-term psychiatric sample. SUBJECTS AND RESEARCH
      DESIGN: Data included an assessment of 163 patients' characteristics,
      corresponding to groups of the RUG-T18, and detailed measurement of nursing staff
      care over a 24-h period. RESULTS: 'Severe behavioural problems' was the most
      frequent RUG-T18 category. There were significant differences in the spent time
      of care in the different groups and high variability in the distribution of time
      of care within groups and in the total sample. CONCLUSIONS: The RUG T-18 system
      should be improved to become a useful case mix system in long-term psychiatric
      inpatients. The high variance intragroups could be minimized improving the
      psychopathological aspects of the system.

PMID- 15720496
TI  - Continuity of care in psychiatric post-ward outpatient services--conceptions of
      patients and personnel concerning factors contributing to the continuity of care.
AB  - A structural change of the psychiatric services was started in Finland in the
      1980s. Its primary objective was to shift the main emphasis from hospital to
      outpatient services. Hence, the number of psychiatric beds has declined to a
      third of the maximum rate, inpatient periods have shortened and the number of
      outpatient appointments has increased significantly. International research shows
      that when the emphasis of psychiatric services shifts to outpatient services and
      hospitalization becomes short-term, diverse individual alternatives are needed to
      support patients' coping. Several Finnish psychiatric hospitals initiated in the
      1990s outpatient services provided at inpatient wards, which means, that after
      the period of hospitalization, further care is provided to the patient at the
      same ward where s/he was hospitalized. The purpose of this study was to describe
      and analyse the conceptions of patients, ward personnel, outpatient services
      personnel and administrative personnel in psychiatric units concerning the
      factors improving the continuity of care. A phenomenographic approach was used
      and the objective was to find the different empirical variations of the
      conceptions, through which people experience, comprehend and become conscious of
      the phenomena in the surrounding world. The data were gathered by interviewing
      post-ward outpatients (n=5), personnel at psychiatric wards and in outpatient
      services (n=18) and administrative personnel in psychiatric units (n=5). As a
      result of the analysis seven categories of the factors improving the continuity
      of care were formed: (1) adherence to a good cooperative relationship; (2)
      adherence to the care environment; (3) flexibility in tailoring care; (4) active
      maintenance of contacts in care; (5) constant possibility to contact the ward;
      (6) up-to-date patient data; and (7) active cooperation between outpatient
      services and other collaborators.

PMID- 15720498
TI  - Asylum nursing in the UK at the end of the Victorian era: Hill End Asylum.
AB  - This paper explores aspects of asylum care at the beginning of the 20th century.
      Archival materials from Hill End, the Hertford County Asylum, provide a single
      historical case study. The study focuses on the methods and standards by which
      asylum nursing was monitored and also examines aspects of the origins and work
      life of the nursing staff. Standards of care were monitored by a number of
      official bodies visiting the asylum, whilst the medical superintendent's role
      focused on the supervision and disciplinary control of nursing staff. Evaluation
      reports at the time were largely favourable in relation to the care given in Hill
      End Asylum. However, the reports were based on the relatively limited
      expectations of the time: primarily relating to the cleanliness, quietness and
      lack of overt complaints regarding care from patients. Further measures reported
      related to: death rates, wet beds, numbers of staff dismissed, together with the
      use of mechanical restraints and seclusion. Nursing staff in the asylum were not
      normally recruited locally and frequently stayed for only short periods of time.
      Training provided was very limited at Hill End although a national nurse training
      scheme was well established by this time. The nursing issues important within the
      asylum were common to all asylums at the time, and some are still significant
      today. This paper provides an insight into the historical development of the
      mental health nursing profession in the UK and its relationship with the medical
      profession. It also provides evidence that current attempts to monitor the
      quality of care through clinical governance processes are far from new.

PMID- 15720497
TI  - An exploration of factors affecting the implementation of a randomized controlled
      trial of a transitional discharge model for people with a serious mental illness.
AB  - Information about the contexts in which trials are carried out helps to identify
      confounding influences on the application of a trial. Furthermore, the ways in
      which context and implementation of trials influence participation are
      particularly important for trials which utilize people as part of the
      intervention. This is particularly likely in the mental health and psychosocial
      fields. The researchers used mixed methods to identify quality issues encountered
      during the conduct of a trial, aiming to explore process and contextual factors
      encountered during its implementation in a mental health setting. Staff and peer
      volunteers who contributed to the intervention provided information on
      implementation via diaries and group meetings. Findings in this paper relate to
      staff feedback. By providing an insider view, researchers were able to highlight
      the importance of obtaining feedback on implementation. Findings relate to the
      context of the study, particularly organizational, practitioner and trial
      preparation issues and illustrate the importance of building quality assurance
      mechanisms into research plans, such as monitoring and feedback processes. The
      issue of 'people involvement' in trial delivery requires sensitive management and
      flexibility in both preparation and delivery.

PMID- 15720499
TI  - Releasing the therapeutic potential of the psychiatric nurse: a human relations
      perspective of the nurse-patient relationship.
AB  - In psychiatry mental health nurses form the largest professional discipline
      providing care on an everyday basis for sustained periods. Mental health nurses
      therefore are in a pivotal position to establish valued therapeutic alliances. In
      practice, however, a disproportionate amount of nursing time is taken up by
      administration, time spent talking to patients is minimal and when interactions
      do occur they remain notionally therapeutic and often are not theoretically
      informed. This noted paucity of therapeutic contact is antithetical to the
      aspirations of service users who increasingly are asking for a more skilled
      approach to the talking-listening that occurs in the therapeutic encounter. It is
      hypothesized by the present authors that an object-relations perspective of the
      nurse-patient relationship could release the largely untapped therapeutic
      potential of the psychiatric nurse by (1) bridging the gap between theory and
      practice and (2) providing a professional identity from within which nurses can
      begin to 'get to know' and understand the predicament of the patient with severe
      mental illness.

PMID- 15720500
TI  - Advocacy in practice: the experiences of independent advocates on UK mental
      health wards.
AB  - Independent advocacy in mental health has become increasingly valued in the UK
      although little work has examined the day-to-day experiences of advocates
      themselves. This article reports on a small-scale exploratory qualitative study
      of practising advocates' experiences of their work in acute and continuing care
      wards. The project results from collaboration between members of the UK Advocacy
      Network and the Department of Mental Health and Learning Disability at the
      University of Sheffield. Although the findings will be of interest to any
      professional allied to these areas they are particularly relevant to mental
      health nurses wishing to increase their knowledge of advocacy and gain a fresh
      perspective on inpatient care. The findings reveal difficulties inherent in
      advocacy practice as well as the nature and importance of good working
      relationships between advocates and clinicians. Despite acknowledging such
      relationships frequently exist, advocates can still encounter ignorance of their
      role and opposition to their presence. The clearest implication of the findings
      is the need for greater training of nurses and other clinicians in the role of
      the advocate.

PMID- 15720501
TI  - Transcultural nursing: the relationship between individualist ideology and
      individualized mental health care.
AB  - This article attempts to clarify and underpin the view that individualized mental
      health nursing is culture biased and politically instrumental, adding weight to
      the transcultural argument that mental health care should be more culture
      sensitive than is often the case within conventional UK settings. It examines the
      political history of individualist ideology, and then uses social conflict theory
      to explore the potentially counter-therapeutic relationship of individualism and
      individualized nursing care in the UK mental health sector. The article
      challenges the widespread idea that individualized mental health nursing is
      'liberal', 'democratic', 'holistic' and 'scientific', and in so doing extends the
      transcultural agenda to large scale infracultural differences within the UK
      population. It also explores the potential for policy change towards a more
      pluralistic service, and outlines some of the practical steps which may be taken
      to access alternative care approaches. It is a power analysis, which may be of
      transferable value to nurses in mental health care inpatient units where
      conventional individualized approaches are failing to reintegrate service users
      into the community. A glossary of terms is presented at the end of this article.

PMID- 15720502
TI  - Experience of implementing an adult educational approach to treating anxiety
      disorders.
AB  - This paper describes the background to the development and delivery of a self
      help package for anxiety disorders. Evidence of effectiveness is summarized. The
      paper outlines the intervention and describes the experience of two mental health
      nurses, who set out to assess its acceptability, evaluate its outcomes in routine
      clinical practice and assess the feasibility of its delivery by mental health
      nurses. Acceptability of the intervention was high, judged by retention and
      attendance rates. The pilot study produced promising clinical outcomes,
      especially for people with depression secondary to anxiety. Clinical measures
      showed significant improvements from pre-course to 6-month follow-up in anxiety,
      psychological well-being and depression. The outcomes suggest that appropriately
      trained mental health nurses could deliver the intervention as a routine
      treatment. The paper concludes by discussing future plans, including a randomized
      controlled trial and implementation in primary care.

PMID- 15720503
TI  - Hope makes a difference.
AB  - Hope. It is a word that is often used but one which we do not stop to think
      intentionally about. It may be difficult to define, and frequently many come to
      know it more by its absence. Nurses espouse the value of hope, but it is a
      concept that often seems elusive when one is trying to put it into practice. The
      author suggests that hope is at the heart of psychiatric nursing practice and
      provides insights and reflections about how it has made a difference in the lives
      of individuals.

PMID- 15720504
TI  - Coercion or collaboration? Nurses doing research with people who have severe
      mental health problems.
AB  - Nurses should address the concerns of service users in research and engage in
      collaborative work with them. Doing this presents ethical dilemmas, not least
      around the issues of assessing capacity and informed consent to participation in
      research. The view that judgement regarding the capacity to consent is solely the
      responsibility of a consultant psychiatrist is challenged as inadequate. The
      concept of 'moral discourse' (Pike 1991) is used to understand the process by
      which the assessment of capacity may be carried out. This is illustrated by the
      application of the concept in a qualitative research study carried out to explore
      what makes mental health services accessible to women with children. The role of
      the mental health nurse entails surveillance and the development of expertise in
      negotiating compliance with treatment programmes. The paper outlines the measures
      taken to ensure that service users felt empowered, rather than coerced, to
      participate in this study. While Community Mental Health Team workers were
      engaged in 'moral discourse' in respect of participation by service users in the
      study, there were difficulties in engaging General Practitioners. However, there
      was evidence that women themselves felt empowered both to express interest in
      participating and to withdraw if they so wished.

PMID- 15720505
TI  - A study on how mental health practitioners address ethical issues in clinical
      audit.
AB  - Although much debate has taken place within the literature on the differences
      between research and clinical audit, the ethical dimensions of audit have
      frequently been neglected. Furthermore, no research has of yet explored what
      ethical issues auditors consider in relation to their projects or how they manage
      them in practice. Using data collected from audit documentation, semi-structured
      interviews and a researcher-administered questionnaire, this study sought to
      advance this position by exploring how 14 clinicians undertook audits in one
      mental health Trust addressed the ethical dimensions of their project. Analysis
      of the data revealed that the Trust had no formal mechanisms for reviewing and
      monitoring audit projects whilst other informal mechanisms were not utilized by
      all auditors. A number of projects had contact with both clinicians and service
      users through interviews, focus groups and questionnaires; however, issues such
      as informed consent, confidentiality and anonymity were not adequately addressed
      by auditors. The implications of these findings are discussed and recommendations
      for practice outlined.

PMID- 15720506
TI  - Proposed changes to the Mental Health Act of England and Wales--research
      investigating the debate.

PMID- 15720510
TI  - Approaches in the safety evaluations of veterinary antimicrobial agents in food
      to determine the effects on the human intestinal microflora.
AB  - The administration of antimicrobial agents to livestock creates potential for
      antibiotic residues to enter the food supply and be consumed by humans.
      Therefore, as a process of food animal drug registration, national regulatory
      agencies and international committees evaluate data regarding the chemical,
      microbiologic, pharmacokinetic, pharmacodynamic, pharmacologic, toxicologic, and
      antimicrobial properties of veterinary drugs to assess the safety of ingested
      antimicrobial residues to consumers. Currently, European, Australian and United
      States guidelines for veterinary drug registration require a safety assessment of
      microbiologic hazards from consumption of antimicrobial residues taking into
      account the potentially adverse effects on human intestinal microflora. The main
      concerns addressed are selection of resistant bacteria in the gastrointestinal
      tract and disruption of the colonization barrier of the resident intestinal
      microflora. Current requirements differ among national agencies. Efforts are
      ongoing internationally to review and harmonize approaches and test methods and
      protocols for application to these microbiologic safety evaluations of
      antimicrobial drug residues in food. This review describes the background to
      current regulatory approaches used in applying in vitro and in vivo methods to
      set a microbiologic acceptable daily intake for residues in food derived from
      animals treated with an antimicrobial agent. This paper also examines the current
      research needs to support these evaluations.

PMID- 15720511
TI  - Population pharmacokinetics of isoniazid in the treatment of Mycobacterium
      tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta
      africana).
AB  - We recently described the clinical presentation and treatment of 18 elephants
      from six herds infected with TB. Treatment protocols and methods varied between
      herds to include both oral and rectal dosing using multiple drug doses and
      formulations. In this paper we present information regarding the pharmacokinetics
      (PK) of isoniazid (INH) in elephants and provide suggestions regarding initial
      treatment regimens. Forty-one elephants received INH daily by either oral or
      rectal administration with different formulations. Population PK analysis was
      performed using Non-linear Mixed Effect Modeling (NONMEM). Results of oral
      administration indicated that compared with premixed INH solution, the drug
      exposure was highest with a suspension prepared freshly with INH powder. When INH
      was concomitantly given as an admixture over food, Tmax was delayed and
      variability in drug absorption was significantly increased. Compared with oral
      administration, similar drug exposures were found when INH was dosed rectally.
      The data generated suggest that a starting dose of 7.5 mg/kg of INH is
      appropriate for initial TB treatment in elephants when premixed solution is
      administered directly into the oropharynx or rectal vault and 4 mg/kg are when
      INH is administered following immediate suspension from powdered form.

PMID- 15720512
TI  - Pharmacodynamics of ibafloxacin in micro-organisms isolated from cats.
AB  - The pharmacodynamic properties of ibafloxacin were investigated in micro
      organisms isolated from cats. Minimal inhibitory concentrations (MIC) of
      ibafloxacin (racemate, R- and S-enantiomers) and its metabolites (7-hydroxy- and
      8-hydroxy-ibafloxacin) and time-kill kinetics were determined against Gram
      negative and Gram-positive bacteria isolated from dermal and respiratory and
      urinary tract infections in cats. Racemic ibafloxacin has a broad spectrum of
      bactericidal activity against Gram-negative and some Gram-positive bacteria.
      Escherichia coli and Pasteurella, Klebsiella and Staphylococcus spp. are commonly
      isolated from feline infections and all are susceptible to ibafloxacin (MIC90 <
      or = 0.5 microg/mL), whereas Pseudomonas aeruginosa, Proteus mirabilis and
      Streptococcus spp. are considered intrinsic resistant. Microbiological activity
      resides primarily in the S-enantiomer of ibafloxacin whereas the R-enantiomer is
      less active. Killing curves using concentrations of racemic ibafloxacin and 8
      hydroxy-ibafloxacin, which are representative of the in vivo situation observed
      in cats, showed at least 99.9% reduction in viable bacterial isolates from feline
      clinical samples over 24 h. Bacterial eradication was achieved in cats with
      Cmax/MIC and AUC/MIC values much lower than the target values previously
      established in man and laboratory animals. Additional studies in dogs and cats
      are necessary to define more clearly the surrogate markers of antibacterial
      activity (i.e. Cmax/MIC, AUC/MIC ratios), which are associated with a good
      clinical response.

PMID- 15720513
TI  - Pharmacokinetics of ibafloxacin in healthy cats.
AB  - The pharmacokinetics of ibafloxacin following single and repeated administration
      of an oral gel formulation and the effect of food intake were investigated in
      cats. Ibafloxacin is a chiral fluoroquinolone available for clinical use as a
      racemic mixture of the R- and S-enantiomers. Plasma concentrations of ibafloxacin
      and its metabolites were determined using microbiological, LC-MS-MS and
      enantioselective capillary zone electrophoresis assays. Ibafloxacin was absorbed
      rapidly [time of maximum concentration (tmax) 2-3 h], reaching a mean maximum
      concentration (Cmax) of approximately 2.1 and 1.6 microg/mL for R- and S
      ibafloxacin, respectively, following a single oral administration of the racemate
      at 15 mg/kg. Once absorbed, ibafloxacin was metabolized to 7-hydroxy-ibafloxacin
      and mainly to 8-hydroxy-ibafloxacin. Following repeated oral administration,
      significant increases in Cmax and AUC of ibafloxacin and its less active
      metabolites (racemic or enantiomers) were observed between the first and the
      tenth day of treatment. This twofold exposure increase in concentrations of
      ibafloxacin and its metabolites may contribute additionally to the efficacy of
      this drug in the treatment of feline bacterial infections. Single and repeated
      doses of ibafloxacin were well tolerated by cats. Food promoted the absorption of
      ibafloxacin, doubling Cmax and increasing AUC and slightly delaying tmax. High
      concentrations of the metabolites, mainly 8-hydroxy- and 7-hydroxy-ibafloxacin
      were excreted in urine, either unchanged or as glucurono-conjugates.

PMID- 15720514
TI  - Clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine in
      a Streptococcus equi subsp. zooepidemicus infection model in ponies.
AB  - Tissue chambers, implanted subcutaneously in the neck in six ponies, were
      inoculated with Streptococcus equi subsp. zooepidemicus in order to determine the
      clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine
      (TMP/SDZ) against this infection. The TMP/SDZ treatment consisted of one
      intravenous (i.v.) injection of 5 mg/kg TMP and 25 mg/kg SDZ and the same dose of
      TMP/SDZ per os (p.o.), both given 3 h before inoculation. The oral dose was then
      repeated every 12 h for 5 days. TMP/SDZ concentrations in tissue chamber fluid
      (TCF) were above 10 times MIC at the moment of inoculation, and they were
      maintained at this level or higher throughout the duration of treatment.
      Trimethoprim/sulfadiazine treatment resulted in a marked reduction of viable
      bacteria in the tissue chamber but did not eliminate the infection, resulting in
      abscessation from day 19 onwards in all six ponies. This shows that, even when
      TCF is not yet purulent, TMP/SDZ is unable to eliminate the streptococci.
      Therefore, TMP/SDZ should not be the antimicrobial treatment of choice in
      infections in secluded sites in horses.

PMID- 15720515
TI  - Pharmacokinetics of azithromycin after intravenous and intramuscular
      administration to goats.
AB  - Azithromycin is the first of a class of antimicrobial agents designated azalides.
      The aim of the present study was to investigate the disposition pharmacokinetics
      of azithromycin in goats and determine its bioavailability. A cross-over study
      was carried out in two phases separated by 30 days. Azithromycin was administered
      at a single dose of 20 mg/kg body weight by i.v. and i.m. routes. Plasma
      concentrations of azithromycin were determined by a modified agar diffusion
      bioassay. After a single i.v. dose plasma concentrations were best fitted to a
      three-compartment open model. A two-compartment open model with first-order
      absorption fitted best after i.m. administration. The values of the
      pharmacokinetic parameters after i.v. administration were: half-life 32.5 h,
      apparent volume of distribution at the steady-state 34.5 L/kg, clearance 0.85
      L/kg. and mean residence time (MRT) 40.1 h. After i.m. administration half-life
      of 45.2 h, a MRT of 60.3 h, maximum plasma concentration 0.64 mg/L and a
      bioavalability 92.2% were obtained. The pharmacokinetic parameters of
      azithromycin after i.m. administration, principally its long half-life and high
      bioavailability, could provide an alternative to the oral route of administration
      in goats, although more studies are needed to establish a suitable pharmaceutical
      formulation, propose optimun dosage regimens, investigate clinical efficacy and
      study the tolerability of repeated doses.

PMID- 15720516
TI  - Evaluation of the anti-endotoxic effects of polymyxin-E (colistin) in dogs with
      naturally occurred endotoxic shock.
AB  - Endotoxin is a potent stimulator of the inflammatory response and is believed to
      initiate the pathology in gram-negative sepsis. Agents are being searched for
      that bind and neutralize or block the effects of endotoxin. The aim was to study
      the anti-endotoxic effects of polymyxin-E (colistin) in endotoxaemic dogs. The
      study included a total of 30 endotoxaemic dogs, which were divided into two
      groups (control = 15; test = 15) of both sexes, different breeds and ages.
      Hetastarch colloid solution (Expahes,10 mL/kg, i.v.) with lactated Ringer's
      solution (20 mL/kg, i.v., Q12 h) was given to all dogs. While ampicillin was
      administered (Alfasilin, 10 mg/kg, i.m., Q12 h) as an antibacterial to the
      control group, colistin (12,500 IU/kg, i.m., Q12 h) + ampicillin were
      administered to the test group. The clinical examination (body temperature, pulse
      and respiration rates, capillary filling times, peripheral pulse qualities,
      dehydration degrees), hematological and biochemical examinations (WBC, RBC, HGB,
      HCT, thrombocyte, serum urea, creatinine and TNF-alpha) were performed both
      before the treatment, and 2, 4, 12 and 24 h after the treatment. In comparison
      with the control group, it was observed that test group had shorter capillary
      filling time at 24 h (P < 0.001). Moreover, the degree of dehydration in test
      group, was significantly improved at 24 h (P < 0.01). While the differences in
      peripheral pulse qualities significantly differed between 0 and 2 h in controls,
      at 2, 4, 24 h after treatment it was found to be significantly increased when
      compared with 0 h in the test group. Serum TNF-alpha concentrations were
      statistically decreased in the test group between 0 h and other times (P < 0.01).
      When compared with controls, serum TNF-alpha concentrations were lower at 2, 4,
      12 and 24 h in test group (P < 0.05). Results of the study indicated that
      polymyxin-E (colistin) has an anti-endotoxic effect and is safe for the dogs with
      endotoxemia at the dosage used in this study.

PMID- 15720517
TI  - Pharmacokinetics and synovial fluid concentrations of flurbiprofen enantiomers in
      horses: chiral inversion.
AB  - Flurbirpofen (FBP), a member of the 2-aryl propionate nonsteroidal anti
      inflammatory drug class, has potent anti-inflammatory and analgesic properties.
      The commercial preparation is a racemic mixture of the R(-) and S(+) enantiomers
      of FBP. In this study, R(-) and S(+) FBP were used to investigate the metabolic
      chiral inversion. Each enantiomer was administered separately (0.25 mg/kg) and in
      a racemic mixture (0.5 mg/kg) intravenously to horses. Plasma and synovial
      concentration of each enantiomer was determined and the disposition of each was
      analyzed. After intravenous administration of R(-) FBP and S(+) FBP to horses no
      chiral inversion was detected. After the administration of the FBP racemate and
      individual enantiomers no differences were observed between pharmacokinetic
      parameters [t(1/2beta) (h), Cl (L/h.kg), AUC (microg.h/mL), Vss (L/kg) and MRT
      (h)] for R(-) and S(+) FBF. Synovial fluid concentrations of both FBP enantiomers
      were lower than plasma concentrations and no stereoselective differences were
      detected. These data indicate that the disposition of FBF in horses is not
      enantioselective and demonstrate a difference in the pharmacokinetic behavior of
      the enantiomers as compared with other 2-aryl-propionic acids, such as carprofen,
      ketoprofen and vedaprofen in the horse.

PMID- 15720518
TI  - Pharmacokinetics of dexamethasone with pharmacokinetic/pharmacodynamic model of
      the effect of dexamethasone on endogenous hydrocortisone and cortisone in the
      horse.
AB  - A compartmental model was used to describe the pharmacokinetics of dexamethasone
      (DXM) and changes in the plasma concentration of endogenous cortisone (COR) and
      hydrocortisone (HYD) following intravenous (i.v.) administration of DXM (0.05
      mg/kg) in horses. Quantification of DXM, COR and HYD in equine plasma was
      achieved using liquid chromatography interfaced with triple spray quadrupole
      quantum tandem mass spectrometry (LC/TSQ-MS/MS). The median alpha (t(1/2alpha)),
      beta (t(1/2beta)), and gamma (t(1/2gamma)) half-lives were 0.33, 2.2, and 10.7 h
      respectively. The area under the DXM plasma concentration curve (AUC) was 113.5
      ng.h/mL. At 72 h post-DXM administration, the plasma concentration of DXM in all
      horses was below the level of quantification (100 pg/mL). The baseline plasma
      concentration of COR was 3.5 +/- 0.69 ng/mL and declined significantly (P < 0.02)
      to 2.9 +/- 0.86 ng/mL at 1 h. The nadir in COR plasma concentration was 0.65 +/-
      0.12 ng/mL at 28.8 +/- 9.0 h, and the DXM plasma concentration was 0.19 +/- 0.13
      ng/mL. COR concentration returned to baseline at 96 h. Baseline plasma
      concentration of HYD was 58.8 +/- 11.7 ng/mL and declined significantly (P <
      0.001) to 41.1 +/- 14.9 ng/mL at 1 h following DXM administration but recovered
      to baseline at 96 h. The sensitivity of LC/TSQ-MS/MS allowed complete description
      of the pharmacokinetics of DXM and its effect on plasma concentrations of both
      COR and HYD.

PMID- 15720519
TI  - Superiority of the gastroduodenal safety profile of licofelone over rofecoxib, a
      COX-2 selective inhibitor, in dogs.
AB  - This study assessed the gastroduodenal safety profile of licofelone, a new
      nonsteroidal anti-inflammatory drug with dual inhibitory activity against 5
      lipoxygenase and cyclo-oxygenase (COX), by using endoscopic evaluations and by
      comparing licofelone to rofecoxib, a selective COX-2 inhibitor. Twenty-one dogs
      underwent blinded gastroduodenoscopies, during which the mucosa of the
      gastroduodenal tract was assessed and scored. Blood analyses were monitored on
      days 0 (baseline), 14, 28, 42, and 56. Examinations to detect fecal occult blood
      were performed daily. Dogs were randomly assigned to three groups that received
      either a placebo, licofelone at a dose of 2.5 mg/kg twice daily, or rofecoxib at
      a dose of 0.5 mg/kg daily, respectively. Significant differences between the
      groups in gastric (P = 0.003), duodenal (P = 0.009), and gastroduodenal (P =
      0.002) endoscopic lesion scores were observed at day 56. Rofecoxib-treated dogs
      had more lesions in all areas when compared with placebo-treated dogs, more
      duodenal lesions when compared with licofelone-treated dogs and more lesions than
      they had at baseline. In contrast to licofelone, rofecoxib was found to induce
      significant gastric and gastroduodenal lesions in dogs that lacked pre-existing
      lesions at baseline. Blood analyses and fecal examinations did not reveal
      abnormalities in any of the experimental groups. Treatment with licofelone was
      well tolerated and was shown to be safer than rofecoxib in terms of upper
      gastrointestinal damage. In this way, this study demonstrates the gastroduodenal
      safety profile of licofelone for chronic treatment.

PMID- 15720521
TI  - Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation
      in dogs: verification in a moxidectin-sensitive Australian Shepherd.
AB  - A subpopulation of dogs of the Collie and Australian Shepherd breeds show
      increased sensitivity to central nervous actions of ivermectin, doramectin,
      loperamide, and probably several other drugs. The molecular background for this
      greater sensitivity is a nonsense mutation in the MDR1 efflux pump, which is part
      of the functional blood-brain barrier and normally limits drug penetration into
      the brain. This report describes a rapid PCR-based method for detection of this
      nt230(del4) MDR1 mutation using a small amount of genomic DNA from blood cells.
      Thereby, homozygous intact, homozygous mutated, and heterozygous mutated MDR1
      genotypes can be clearly differentiated by high resolution polyacrylamide gel
      electrophoresis. Using this diagnostic test two Collies and one Australian
      Shepherd were screened for the nt230(del4) MDR1 mutation. The Collies had no
      history of altered drug sensitivity and showed homozygous intact and heterozygous
      mutated MDR1 alleles, respectively. However, the Australian Shepherd developed
      clear signs of neurotoxicity including ataxia, crawling, acoustic and tactile
      hyperexcitability, and miosis after a single dose of moxidectin (400 microg/kg).
      For this dog two mutated MDR1 alleles were detected. This report describes for
      the first time moxidectin neurotoxicosis in a dog with a homozygous MDR1
      mutation.

PMID- 15720522
TI  - Distribution of emamectin benzoate in Atlantic salmon (Salmo salar L.).
AB  - The aims of this study were to investigate the content of emamectin in blood,
      mucus and muscle following field administration of the recommended dose, and
      correlation with sea lice infection on the same fish (elimination study). The
      tissue distribution of tritiated emamectin benzoate after a single oral dose in
      Atlantic salmon was also investigated by means of whole-body autoradiography and
      scintillation counting (distribution study). In the elimination study,
      concentrations of emamectin benzoate reached maximum levels of 128, 105 and 68
      ng/g (p.p.b.) for blood, mucus and muscle respectively, on day 7, the last day of
      administration. From day 7, the concentration in the blood declined until
      concentration was less than the limit of detection on day 77. The concentration
      was higher in mucus compared with plasma (P < 0.05) except on days 7 and 21. The
      concentration of emamectin benzoate decreased gradually from the end of treatment
      (day 7) to day 70 with half-lives of 9.2, 10.0 and 11.3 days in muscle, plasma
      and mucus respectively. The distribution study demonstrated a high quantity of
      radioactivity in mucous membranes (gastrointestinal tract, gills) throughout the
      observation period (56 days). Activity was high in the epiphysis, hypophysis and
      olfactory rosette throughout the study. The highest activity was observed in the
      bile, indicating this to be an important route for excretion. The distribution
      study confirmed the results from the elimination study with respect to
      concentrations in blood, skin mucous and muscle.

PMID- 15720520
TI  - Relationship between plasma concentrations and analgesia after intravenous
      fentanyl and disposition after other routes of administration in cats.
AB  - Data allowing rational use of analgesics in cats are limited. Pharmacokinetics
      and pharmacodynamics of fentanyl were studied in cats. Plasma fentanyl
      concentrations were measured using radioimmunoassay in a crossover study in six
      cats after 10 microg/kg (i.v.) or by application of fentanyl in pluronic lecithin
      organogel (PLO) to the inner ear pinna. On a separate occasion thermal thresholds
      were measured after i.v. fentanyl (10 microg/kg) or saline. Plasma fentanyl
      concentrations reached 4.7-8.31 ng/mL 2 min after i.v. administration and were
      undetectable after 95 min. Fentanyl was not detected in plasma at any time after
      PLO use. Thermal thresholds did not change following saline administration but
      were increased above baseline from 5 to 110 min after i.v. fentanyl. In this
      model a plasma concentration of >1.07 ng/mL was required to provide analgesia.
      Plasma concentrations were measured in additional cats after intranasal or oral
      dosing (2 microg/kg) and after 30 microg/kg in PLO gel. After oral and nasal
      dosing, Cmax values were 0.96 and 1.48 ng/mL at 5 and 2 min, respectively. Plasma
      fentanyl was not detected after application of the higher dose of fentanyl in
      PLO.

PMID- 15720523
TI  - Influence of marbofloxacin on the pharmacokinetics and pharmacodynamics of
      tolfenamic acid in calves.
AB  - Pharmacokinetic and pharmacodynamic properties of tolfenamic acid (TA) in calves
      were determined in serum and fluids of inflamed (carrageenan administered) and
      non-inflamed subcutaneously implanted tissue cages after intramuscular
      administration both alone and in combination with marbofloxacin (MB). MB
      significantly altered the pharmacokinetics of TA: mean values were Cmax = 2.14
      and 1.64 microg/mL, AUC = 27.38 and 16.80 microg.h/mL, Vd(area)/F = 0.87 and 1.17
      L/kg, and ClB/F = 0.074 and 0.128 L/kg/h, respectively, after administration of
      TA alone and TA + MB. T(1/2)K10 and MRT were not significantly different for the
      two treatments. The pharmacodynamic properties of TA were not influenced by MB co
      administration, in spite of the alterations in some TA pharmacokinetic
      parameters. TA inhibited prostaglandin E2 (PGE2) synthesis in vivo in
      inflammatory exudate by 50-88% for up to 48 h after both TA treatments.
      Inhibition of synthesis of serum thromboxane B2 (TxB2) ex vivo ranged from 40 to
      85% up to 24 h after both TA and TA + MB. From the derived pharmacokinetic and
      eicosanoid inhibition data for TA, pharmacodynamic parameters for serum TxB2 and
      exudate PGE2 inhibition expressing efficacy (Emax = 78.1 and 97.5%), potency
      (IC50 = 0.256 and 0.265 microg/mL), sensitivity (N = 1.96 and 2.29) and the
      pharmacokinetic parameter equilibration time (t(1/2)K(e0) = 0.695 and 24.0 h),
      respectively, were determined. In this model TA was a nonselective inhibitor of
      cyclo-oxygenase (COX) (COX-1:COX-2 IC50 ratio = 1.37). TA, both alone and co
      administered with MB, did not affect leucocyte numbers in exudate, transudate or
      blood. Partial attenuation of skin temperature rise over inflamed tissue cages
      and reduction of zymosan-induced skin swelling were recorded after administration
      of TA and TA + MB with no significant differences between the two treatments.
      These data provide a basis for the rational use of TA in combination with MB in
      calf medicine.

PMID- 15720524
TI  - Antimicrobial susceptibility of animal strains of Salmonella enterica isolated in
      Italy from 2001 to 2003.

PMID- 15720525
TI  - Hepatitis B virus: significance of genotypes.
AB  - Hepatitis B Virus (HBV) genotypes have come of age. The concept that HBV
      genotypes may influence the course of disease and relevant biological differences
      has now been recognised. However, there are still major gaps in our knowledge.
      Most clinical data come from Asia and describe findings in patients infected with
      genotypes B and C. Large scale studies with genotypes A and D as found in Europe
      or A, D and E from Africa are urgently needed to broaden our understanding.
      Experimental data which explain in vivo findings in terms of differences in
      molecular biology in vitro are still in the beginning. The succeeding years will
      see many interesting studies which will aid our understanding of how variants and
      genotypes of HBV influence the spectrum of disease in people infected with HBV.

PMID- 15720526
TI  - Intrahepatic and peripheral blood virus-specific cytotoxic T lymphocyte activity
      is associated with a response to combination IFN-alpha and ribavirin treatment
      among patients with chronic hepatitis C virus infection.
AB  - This report describes an association between intrahepatic and peripheral blood
      cytotoxic T lymphocytes (CTL) activity present prior to receiving treatment, and
      a response to combination interferon-alpha (IFN-alpha) and ribavirin therapy for
      chronic hepatitis C virus (HCV) infection. Recombinant vaccinia virus constructs
      were used to expand and detect cytotoxic effectors against the entire genotype 1a
      HCV polyprotein. Six patients with a sustained response to therapy were
      significantly more likely to display intrahepatic and peripheral blood HCV
      specific CTL activity than patients who relapsed or had no treatment response.
      Limited longitudinal data suggested that rather than combination therapy acting
      to enhance the CTL response to achieve viral clearance, detectable CTL prior to
      treatment increases the likehood of the host responding to the direct antiviral
      activity of IFN-alpha and ribavirin.

PMID- 15720527
TI  - Enhanced expression of suppressor of cytokine signalling-1 in the liver of
      chronic hepatitis C: possible involvement in resistance to interferon therapy.
AB  - Interferon-alpha (IFN-alpha) is widely used in the treatment of chronic hepatitis
      C (CHC). The suppressor of cytokine signalling (SOCS) family has been implicated
      in the regulation of JAK-STAT signalling, including IFN signalling. The negative
      effect of SOCS expression on the response of CHC to IFN-alpha is demonstrated
      here. The transcriptional levels of SOCS-1 and -3 in the livers of 21 patients
      with CHC and eight controls were investigated by quantitative reverse
      transcription-polymerase chain reaction. We established stable transfectants of
      SOCS-1 in a human hepatoma cell line, PLC/PRF/5 and analysed the effects of SOCS
      1 on the phosphorylation of IFN-alpha-induced STAT-1 tyrosine by immunoblotting
      and the expression of antiviral genes by Northern blot. A prospective cohort
      study on SOCS-1 expression and clinical outcome was carried out in 77 patients
      with CHC who received IFN therapy. SOCS-1, but not SOCS-3, transcripts in the
      livers of CHC were significantly higher than controls (P < 0.005). IFN-alpha
      induced STAT-1 phosphorylation and the expression of antiviral genes were
      inhibited in SOCS-1-transfected cells. Patients showing high SOCS-1 expression in
      the liver had a significantly lower rate of sustained virological response (SVR)
      to IFN therapy than those with low SOCS-1 expression (P = 0.0014). A multivariate
      analysis performed with host factors revealed that SOCS-1 staining in the liver
      can serve as a significant predictor for IFN SVR (P = 0.004). SOCS-1 expression
      is enhanced in the livers of CHC patients and might be involved in resistance to
      IFN therapy.

PMID- 15720528
TI  - Interferon sensitivity-determining region of nonstructural region 5A of hepatitis
      C virus genotype 1b correlates with serum alanine aminotransferase levels in
      chronic infection.
AB  - The mutations in the interferon (IFN) sensitivity-determining region (ISDR) of
      nonstructural region 5A (NS5A) of hepatitis C virus (HCV) have been correlated
      with response to IFN therapy. NS5A appears to disrupt a host antiviral pathway
      that plays a role in suppressing virus replication and protects hepatocytes from
      apoptosis. We assessed whether ISDR correlates with viral load and serum alanine
      aminotransferase (ALT) levels. Serum viral load and ALT levels were prospectively
      measured bimonthly by HCV core protein assay and monthly, respectively, for 22
      months in 87 patients chronically infected with HCV genotype 1b. ISDR of HCV was
      directly sequenced from the products of reverse transcription and polymerase
      chain reaction of HCV RNA. Five patients had four or more substitutions (mutant
      type), 33 had 1-3 (intermediate type), and 49 had no substitutions (wild type) in
      ISDR. The numbers of substitutions in ISDR were inversely correlated with mean
      viral load over a 22-month period (r = 0.292, P = 0.0060) and directly with mean
      serum ALT levels (r = 0.360, P = 0.0006). The numbers of substitutions in ISDR
      was significantly larger in the patients with changes of viral load more than
      fivefold during the 22 months (1.4 +/- 2.4) than in those without changes (0.6 +/
      0.8) (P = 0.0188). The present study demonstrates that the patients with more
      substitutions in ISDR had significantly higher serum ALT levels and smaller viral
      load. These results suggest that NS5A with more substitutions in ISDR may lose
      the ability to block host antiviral pathways and to protect hepatocytes from
      apoptosis.

PMID- 15720529
TI  - Hot-spot mutations in hepatitis B virus core gene: eliciting or evading immune
      clearance?
AB  - The biological implications of substitutions L60V and I97L in the core (c) gene
      of hepatitis B virus (HBV) were investigated in order to determine whether they
      could change the immunogenicity of HBcAg or influence the immune response in
      mice. Three strains of recombinant adenoviruses--AdHBV-WT, AdHBV-L60V and AdHBV
      I97L--containing wild-type or mutant HBV genomes were constructed using the
      AdEasy system and used to infect BALB/c mice intranasally. Infected mice produced
      anti-HBc efficiently to comparable levels. IgG1 and IgG2a specific for HBcAg were
      present in mice sera, and the response was dominated by IgG2a. The lymphocyte
      proliferative response specific for HBcAg was assessed by [3H]-thymidine uptake.
      We found that AdHBV-WT induced a stronger T-cell proliferation response than
      AdHBV-L60V and AdHBV-I97L. In conclusion, the L60V and I97L substitutions had no
      influence on humoral immune responses, but could downregulate T-cell responses to
      HBcAg, suggesting that L60V and I97L were immune escape mutants.

PMID- 15720530
TI  - Long-term follow-up of chronic hepatitis B after the emergence of mutations in
      the hepatitis B virus polymerase region.
AB  - Treatment of chronic hepatitis B has been greatly improved by the use of
      lamivudine, but mutations occur in the polymerase region of hepatitis B virus
      (HBV) and lamivudine-resistant mutants frequently develop. The emergence of
      lamivudine-resistant strains of HBV is a problem for treating chronic hepatitis B
      using lamivudine. We observed biochemical and virological changes in 15 patients
      with chronic hepatitis B for a median period of 29 months (range: 4-42 months)
      after the emergence of lamivudine-resistant mutants of HBV. Patterns of mutation
      of the polymerase gene were examined by sequencing the LLAQ motif in domain B and
      the YMDD motif in domain C. Exacerbation of liver dysfunction occurred in 14
      (93.3%) of the 15 patients at a median of 4 months after the emergence of
      mutations. However, exacerbation of liver dysfunction was observed only in four
      patients (26.7%) at the time of appearance of the first mutations and in 80.0% of
      the patients at the time of appearance of the second mutations. Increase in serum
      alanine aminotransferase (ALT) levels was significantly greater at the time of
      appearance of second mutations (P = 0.0096). In most cases, wild-type HBV was
      mutated with the substitution of only rtM204I at first, and rtL180M/M204I
      mutations and then rtL180M/M204V mutations subsequently appeared. Further
      mutations of the polymerase region caused clinical deterioration. Thus as
      mutations emerge in the polymerase region, the clinical outcome deteriorates.
      Thus, monitoring the patterns of mutation of the polymerase gene is useful when
      using lamivudine for treating HBV.

PMID- 15720531
TI  - Low frequency of mutations in the X gene, core promoter and precore region of
      hepatitis B virus infected Vietnamese.
AB  - Numerous mutations in the hepatitis B virus (HBV) genome have been described, but
      in most cases their role in the pathogenesis of HBV infection is still unclear.
      Therefore, we analysed specific mutations in HBV-infected Vietnamese patients and
      assessed their potential relationship with their clinical outcome. A total of 153
      HBV-infected Vietnamese patients with well-characterised clinical profiles were
      enrolled. None of the study participants had a history of alcohol or drug use and
      none received any antiviral or immunosuppressive therapy before or during the
      course of this study. The HBx- and core promoter regions were analysed by
      sequencing. The majority of isolates corresponded to genotype A. The presence of
      hepatitis B e antigen (HBeAg) was associated with significantly higher viral
      loads in the chronic HBV-infection group (P = 0.026). Double mutations in the
      core promoter (1762/1764) were more frequent in those with cancer than in
      noncancer patients (P < 0.01). Mutations at nucleotide (nt) 1766/1773 were found
      at low prevalence but with no obvious association to clinical presentation.
      Cytosine at nt 1858 was predominant but the stop codon mutation in the precore
      region was not detected. In the study, 4/48 hepatocellular carcinoma (HCC)
      patients revealed truncated HBx, whilst the serine to alanine mutation (codon 31)
      of HBx was more prevalent in cancer patients than in asymptomatic HBV carriers (P
      < 0.01). Thus, the low frequency of mutations indicates the relation of the
      absence of antiviral pressure in this population. The exclusively found
      prevalence of certain mutations detected in those with HBV-related carcinoma
      nevertheless indicates a degree of association with disease progression.

PMID- 15720532
TI  - Quantification of the relative levels of wild-type and lamivudine-resistant
      mutant virus in serum of HBV-infected patients using microarray.
AB  - During the course of lamivudine administration in hepatitis B virus (HBV)
      infected patients, a dynamic development of the viral population in serum is
      observed. Total HBV level is initially reduced, then lamivudine-resistant mutants
      appear, and finally, the viral level is increased. All methods of mutant
      detection so far described can only identify mutants in the serum, and cannot
      determine the proportion of those mutants. In this paper, we report the
      development of a novel technique that can quantify the relative proportion of
      mutants in serum utilizing gene microarray technology. Based on the nucleotide
      sequence at the loci of the mutations in lamivudine-resistant HBV mutants, 28
      probes were designed and dotted on glass film to prepare the oligonucleotide
      microarray. Ten standard curves were established by employing 15 reference
      plasmids as templates. Ten standard math functions were simulated, which allowed
      quantification of the proportion of mutants in the sample by measuring the value
      of fluorescent intensity on the microarray. By utilizing the standard math
      function, the relative proportion of two different mutation sequences in the
      mixed template could be detected with an error <10%. The HBV-lamivudine
      oligonucleotide microarray is reliable to quantify the relative proportion of
      wild-type HBV vs HBV mutants in patient's sera.

PMID- 15720533
TI  - Factors associated with the initiation of alpha-interferon treatment in Medicaid
      patients diagnosed with hepatitis C.
AB  - We aimed to determine rates of treatment with alpha-interferon medication in
      patients diagnosed with hepatitis C virus (HCV), to ascertain the prevalence of
      selected conditions that could influence initiation of interferon treatment, and
      to examine the association between the presence of these conditions and
      interferon treatment. A nested case-control design was used in California
      Medicaid (Medi-Cal) claims data covering the period from 1 January 1996 to 30
      June 2002. Interferon-treated cases and non-treated controls were selected in a 1
      : 2 ratio that matched the length of the observation period and year of index HCV
      diagnosis. Predictor variables examined in bivariate and multivariate analyses
      included demographics, substance abuse and dependence, psychotropic drug use,
      selected chronic conditions and medical utilization. The proportion of eligible
      subjects diagnosed with HCV and treated with interferon ranged from 10.7 to
      13.9%. There were 529 treated cases that met the eligibility criteria and 1058
      non-treated HCV patients selected as controls. Multivariate factors that
      increased the likelihood of treatment were a liver biopsy, a diagnosis of mild
      liver disease, a diagnosis of psoriasis, antidepressant use and classification of
      race/ethnicity as 'other'. A decreased likelihood of treatment was linked to age
      > or =65 years, a diagnosis of kidney disease, one to four emergency visits and
      five or more emergency visits. The proportion of patients receiving interferon
      treatment in the Medi-Cal-insured population was low compared with published
      rates in HCV patients in other general medical settings. The diverse factors
      linked to initiation of HCV therapy raise compelling questions for further
      research.

PMID- 15720534
TI  - Three-phase sequential combined treatment with lamivudine and interferon in young
      patients with chronic hepatitis B.
AB  - Alpha-interferon (IFN) or lamivudine monotherapy are ineffective in treating
      chronic HBeAg positive patients with high viral load and low alanine
      aminotransferase (ALT) levels. We investigated whether priming lamivudine
      treatment might enhance the antiviral and immunostimulant action of
      lamivudine/IFN combination in young tolerant patients. Eleven chronic HBeAg
      positive patients received: 100 mg/day lamivudine for 3 months followed by IFN 5
      MU/m2/tiw with lamivudine 100 mg/day for 6 months and then lamivudine alone 100
      mg/day for 9 months. Quantitative hepatitis B virus (HBV)-DNA was evaluated
      during treatment and core-promoter, precore and polymerase HBV mutants were
      detected by direct sequencing at the end of therapy. Serum HBV-DNA levels dropped
      during lamivudine monotherapy and in combination with IFN. After IFN withdrawal,
      viraemia transiently increased to high levels in five of 11 (45%) patients who
      showed rt M204V/I lamivudine mutant resistant. Two patients cleared HBeAg without
      anti-HBe seroconversion. One patient presented core-promoter (A1762T/G1764A) and
      precore stop codon mutations. Hence, three-phase sequential combined
      lamivudine/IFN treatment reduced HBV-DNA serum level, but did not lead to HBeAg
      and HBV-DNA clearance in these highly viraemic, normal ALT patients.
      Lamivudine/IFN combination did not prevent the emergence of YMDD lamivudine
      resistance. New schedules of antiviral treatments must be evaluated in this
      population at risk of disease progression.

PMID- 15720535
TI  - Clinical outcome and virological characteristics of hepatitis B-related acute
      liver failure in the United States.
AB  - The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV
      infection is unclear. In this study, we aimed to evaluate the clinical and
      virological features of patients with hepatitis B-related acute liver failure
      (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients
      with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV
      genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants
      among patients with HBV-ALF were compared with a cohort of 530 patients with
      chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41
      years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found
      in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual
      variants were detected in 32 and 44% of patients, respectively. Twenty-three
      (68%) patients survived: 14 after liver transplant, nine without transplant.
      Older age was the only independent factor associated with poor outcome. Compared
      with patients with chronic HBV infection, patients with ALF were more likely to
      be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P <
      0.01). A higher prevalence of HBV genotype D persisted even after matching for
      race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D
      was more frequently found in patients with HBV-ALF than those with chronic HBV
      infection in the US. Further studies are needed to determine if HBV genotypes
      play a role in the outcome of acute HBV infection.

PMID- 15720536
TI  - Impact of interferon-alpha therapy on liver fibrosis progression in patients with
      HBeAg-negative chronic hepatitis B.
AB  - The possible effect of interferon-alpha (IFNa) on liver fibrosis progression has
      not been adequately studied in chronic hepatitis B. We evaluated 147 patients
      with HBeAg-negative chronic hepatitis B who had > or =2 liver biopsies and had
      been treated with IFNa (n = 120) or had remained untreated (n = 27). The median
      interval between the two biopsies was 24 (12-160) months. All biopsies were
      scored blindly by a single liver histopathologist according to the classification
      of Ishak et al. (J Hepatol 1995; 22: 696-699). IFNa induced sustained biochemical
      response in 30, initial response and subsequent relapse in 57 and no response in
      33 patients. Fibrosis improved in 17.5% of treated (sustained responders: 40%,
      relapsers: 9%, nonresponders: 12%) and 4% of untreated patients and worsened in
      34% (sustained responders: 7%, relapsers: 40%, nonresponders: 48%) and 70% of
      cases, respectively (P = 0.002). The annual rate of fibrosis progression was
      worse in the untreated (0.427 +/- 0.119) than in treated patients (0.067 +/-
      0.052, P = 0.001). However, the fibrosis progression rate in the untreated
      patients was not significantly different than the net fibrosis progression rate
      (after subtraction of IFNa duration) in nonresponders or relapsers. In
      multivariate analysis, worse fibrosis progression rate was associated with older
      age (P = 0.010), worse baseline grading score (P < 0.001), lower baseline
      fibrosis (P = 0.035) and the type of response to IFNa (P = 0.032). In conclusion,
      in HBeAg-negative chronic hepatitis B, IFNa significantly reduces the rate of
      fibrosis progression, but such an effect is mainly observed in patients with
      sustained biochemical responses. In relapsers and nonresponders, fibrosis benefit
      equals the treatment period. The strongest factor associated with fibrosis
      progression is the change in necroinflammatory activity.

PMID- 15720537
TI  - Treatment of acute hepatitis C infection in HIV-infected patients: a
      retrospective analysis of eleven cases.
AB  - Studies on hepatitis C virus (HCV) monoinfected patients suggest high sustained
      treatment response rates of up to 98% when interferon monotherapy is administered
      during the acute phase of HCV-infection. To clarify whether early treatment of
      acute hepatitis C is similarly efficient in human immunodeficiency virus (HIV)
      positive patients, we conducted a retrospective survey of HIV-positive patients
      with acute HCV infection. Eleven HIV-positive patients who had been treated with
      interferon or interferon/ribavirin were identified at eight HIV-specialty
      outpatient clinics. The patients had been treated over a median 25 weeks with
      standard interferon (two patients), pegylated interferon (four patients) and
      pegylated interferon in combination with ribavirin (five patients). A post
      treatment response (negative serum HCV-RNA at the end of treatment) was seen in
      10 of 11 patients and HCV-RNA remained undetectable 24 weeks after the end of
      treatment in all the 10 responders. Alanine aminotransferase (ALT) normalized in
      eight patients while two virological responders and one nonresponder showed
      persistent mild ALT elevations. In conclusion, early treatment of acute hepatitis
      C seems to achieve high sustained virological treatment response rates also in
      patients with HIV-infection.

PMID- 15720538
TI  - HBV vaccination in liver transplant recipients: not an effective strategy in the
      prophylaxis of HBV recurrence.
AB  - Anti-HBs immunoglobulins (HBIG) and lamivudine are main options to prevent
      hepatitis B virus (HBV) reinfection after liver transplantation. Although they
      are very effective, development of mutant viruses and high cost of treatment are
      main limitations for their application. Additionally there is an uncertainity for
      the duration of that prophylaxis regimen and its mostly applied indefinitely.
      Recently, post-transplant HBV vaccination is reported to be a cheaper alternative
      prophylaksis strategy, that enables discontinuation of HBIG. To investigate the
      efficacy of HBV vaccination in patients transplanted for HBV cirrhosis, we
      administered double course of double dose recombinant HBV vaccine (Genhavac B;
      containing HBV pre-S1, pre-S2, and S gene products). Vaccination has been started
      1 month after HBIg discontinuation, and lamivudine (100 mg/day) was given
      throughout the study. The first cycle consisted of 0, 1- and 6-month schedule,
      and, in nonresponders, second cycle 0, 1-, 2-month schedule. Fourteen patients
      included into the study. Only one patient seroconverted (an anti-HBs titre of 37
      IU/L) after the first cycle. No other patient responded to second cycle. HBV
      vaccination in the post-transplantation setting does not seems like an effective
      strategy in the prophylaxis of HBV recurrence.

PMID- 15720539
TI  - Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy
      for HBeAg positive chronic hepatitis B.
AB  - The aim of this study was to determine whether the changing patterns of
      quantitative hepatitis B e antigen (HBeAg) levels by serial monitoring could
      predict HBeAg seroconversion and viral breakthrough during lamivudine therapy. We
      retrospectively analysed 340 HBeAg positive naive chronic hepatitis B patients
      treated with lamivudine. The mean duration of lamivudine therapy was 18.7 (range
      6-56) months. The changing patterns and reduction rates of pretreatment HBeAg
      levels by serial monitoring were categorized into three groups: Decrescendo group
      (n = 195), Decrescendo-crescendo group (n = 65) and no changing or fluctuating
      group (n = 80). Of 109 patients who had achieved HBeAg seroconversion, 105
      (96.3%) were included in the decrescendo group. The decrescendo group,
      pretreatment quantitative HBeAg levels, alanine aminotransferase levels, and the
      duration of lamivudine therapy were independent predictive factors for HBeAg
      seroconversion. Of 82 patients who had viral breakthrough, 53 (64.6%) were in the
      decrescendo-crescendo group and 21 (25.6%) were in the no changing or fluctuating
      group. The only predictive factor for viral breakthrough was the changing
      patterns of quantitative HBeAg levels, especially, the decrescendo-crescendo
      group and the no changing or fluctuating group. The mean time of turning points
      in the decrescendo-crescendo group was 7.1 months earlier than the mean time of
      viral breakthrough (9.0 months vs 16.5 months). Therefore, the changing patterns
      of quantitative HBeAg levels by serial monitoring during lamivudine therapy may
      allow not only the prediction of treatment responses, but also an early
      recognition of a viral breakthrough.

PMID- 15720540
TI  - Getting down to malarial nuts and bolts: the interaction between Plasmodium vivax
      merozoites and their host erythrocytes.
AB  - Of the four Plasmodium species that routinely cause malaria in humans, Plasmodium
      falciparum is responsible for the majority of malaria mortality and consequently
      gets most of the headlines. Outside Africa, however, more malaria cases are
      caused by its distant cousin Plasmodium vivax, resulting in a daunting morbidity
      and economic burden for countries across Asia and the Americas. Plasmodium life
      cycles are complex, but the symptoms and pathology of malaria occur during the
      blood phase, when merozoites recognize and invade erythrocytes, initiating a
      developmental programme that culminates in lysis of the erythrocyte and release
      of multiple daughter merozoites. P. vivax merozoites are dependent on a single
      host cell receptor for erythrocyte invasion, the Duffy antigen receptor for
      chemokines, and humans that do not express this receptor on the surface of their
      erythrocytes are immune to P. vivax infection. This essential receptor-ligand
      interaction is addressed from both the host and parasite side in two papers in
      this issue of Molecular Microbiology, with important implications for plans to
      develop a P. vivax vaccine.

PMID- 15720541
TI  - 2004 ASM Conference on the New Phage Biology: the 'Phage Summit'.
AB  - In August, more than 350 conferees from 24 countries attended the ASM Conference
      on the New Phage Biology, in Key Biscayne, Florida. This meeting, also called the
      Phage Summit, was the first major international gathering in decades devoted
      exclusively to phage biology. What emerged from the 5 days of the Summit was a
      clear perspective on the explosive resurgence of interest in all aspects of
      bacteriophage biology. The classic phage systems like lambda and T4,
      reinvigorated by structural biology, bioinformatics and new molecular and cell
      biology tools, remain model systems of unequalled power and facility for studying
      fundamental biological issues. In addition, the New Phage Biology is also
      populated by basic and applied scientists focused on ecology, evolution,
      nanotechnology, bacterial pathogenesis and phage-based immunologics, therapeutics
      and diagnostics, resulting in a heightened interest in bacteriophages per se,
      rather than as a model system. Besides constituting another landmark in the long
      history of a field begun by d'Herelle and Twort during the early 20th century,
      the Summit provided a unique venue for establishment of new interactive networks
      for collaborative efforts between scientists of many different backgrounds,
      interests and expertise.

PMID- 15720542
TI  - Bacterial transcription elongation factors: new insights into molecular mechanism
      of action.
AB  - Like transcription initiation, the elongation and termination stages of
      transcription cycle serve as important targets for regulatory factors in
      prokaryotic cells. In this review, we discuss the recent progress in structural
      and biochemical studies of three evolutionarily conserved elongation factors,
      GreA, NusA and Mfd. These factors affect RNA polymerase (RNAP) processivity by
      modulating transcription pausing, arrest, termination or anti-termination. With
      structural information now available for RNAP and models of ternary elongation
      complexes, the interaction between these factors and RNAP can be modelled, and
      possible molecular mechanisms of their action can be inferred. The models suggest
      that these factors interact with RNAP at or near its three major, nucleic acid
      binding channels: Mfd near the upstream opening of the primary (DNA-binding)
      channel, NusA in the vicinity of both the primary channel and the RNA exit
      channel, and GreA within the secondary (backtracked RNA-binding) channel, and
      support the view that these channels are involved in the maintenance of RNAP
      processivity.

PMID- 15720543
TI  - Severing all ties between mother and daughter: cell separation in budding yeast.
AB  - At the end of nuclear division in the budding yeast, acto-myosin ring contraction
      and cytokinesis occur between mother and daughter cells. This is followed by cell
      separation, after which mother and daughter cells go their separate ways. While
      cell separation may be the last event that takes place between the two cells, it
      is nonetheless under tight regulation which ensures that both cells are viable
      upon separation. It is becoming increasingly clear that the components of the
      cell separation machinery are controlled at various levels, including the
      temporal and spatial regulation of the genes encoding for the components and the
      specific localization of the components to the neck. In addition, these
      regulatory controls are co-ordinated with exit from mitosis, thereby placing a
      mechanistic link between the end of mitosis and cell separation. More
      importantly, the success of the cell separation event is contingent upon the
      presence of a trilaminar septum, whose assembly is dependent on a host of
      proteins which localize to the neck over the span of one cell division cycle.

PMID- 15720544
TI  - Evolution of a phage RuvC endonuclease for resolution of both Holliday and
      branched DNA junctions.
AB  - Resolution of Holliday junction recombination intermediates in most Gram-negative
      bacteria is accomplished by the RuvC endonuclease acting in concert with the
      RuvAB branch migration machinery. Gram-positive species, however, lack RuvC, with
      the exception of distantly related orthologues from bacteriophages infecting
      Lactococci and Streptococci. We have purified one of these proteins, 67RuvC, from
      Lactococcus lactis phage bIL67 and demonstrated that it functions as a Holliday
      structure resolvase. Differences in the sequence selectivity of resolution
      between 67RuvC and Escherichia coli RuvC were noted, although both enzymes prefer
      to cleave 3' of thymidine residues. However, unlike its cellular counterpart,
      67RuvC readily binds and cleaves a variety of branched DNA substrates in addition
      to Holliday junctions. Plasmids expressing 67RuvC induce chromosomal breaks,
      probably as a consequence of replication fork cleavage, and cannot be recovered
      from recombination-defective E. coli strains. Despite these deleterious effects,
      67RuvC constructs suppress the UV light sensitivity of ruvA, ruvAB and ruvABC
      mutant strains confirming that the phage protein mediates Holliday junction
      resolution in vivo. The characterization of 67RuvC offers a unique insight into
      how a Holliday junction-specific resolvase can evolve into a debranching
      endonuclease tailored to the requirements of phage recombination.

PMID- 15720545
TI  - Two substrate-targeting sites in the Yersinia protein tyrosine phosphatase co
      operate to promote bacterial virulence.
AB  - YopH is a protein tyrosine phosphatase and an essential virulence determinant of
      the pathogenic bacterium Yersinia. Yersinia delivers YopH into infected host
      cells using a type III secretion mechanism. YopH dephosphorylates several focal
      adhesion proteins including p130Cas in human epithelial cells, resulting in
      disruption of focal adhesions and cell detachment from the extracellular matrix.
      How the C-terminal protein tyrosine phosphatase domain of YopH targets specific
      substrates such as p130Cas in the complex milieu of the host cell has not been
      fully elucidated. An N-terminal non-catalytic domain of YopH binds p130Cas in a
      phosphotyrosine-dependent manner and functions as a novel substrate-targeting
      site. The structure of the YopH protein tyrosine phosphatase domain bound to a
      model phosphopeptide substrate was solved and the resulting structure revealed a
      second substrate-targeting site ('site 2') within the catalytic domain. Site 2
      binds to p130Cas in a phosphotyrosine-dependent manner, and co-operates with the
      N-terminal domain ('site 1') to promote efficient recognition of p130Cas by YopH
      in epithelial cells. The identification of two substrate-targeting sites in YopH
      that co-operate to promote epithelial cell detachment and bacterial virulence
      reinforces the importance of protein-protein interactions for determining protein
      tyrosine phosphatase specificity in vivo, and highlights the sophisticated nature
      of microbial pathogenicity factors.

PMID- 15720547
TI  - Delineation and characterization of the actin nucleation and effector
      translocation activities of Salmonella SipC.
AB  - Salmonella type III secreted SipC possesses dual functions: translocation of
      effectors and actin modulation. The biological significance of SipC's actin
      nucleation activity in Salmonella-induced actin cytoskeleton rearrangements has
      not been studied. We report here the delineation of the actin nucleation activity
      from the effector translocation activity of SipC. Our data show that the central
      amino acid region (residues: 201-220) is essential for its actin nucleation
      activity and the C-terminal amino acid region (321-409) is required for
      translocation of effectors. A SipC nucleation-deficient mutant, which maintained
      its effector translocation activity, was obtained. This nucleation-deficient
      mutant had significantly reduced ability to induce actin cytoskeleton
      rearrangements, resulting in lower bacterial invasion into HeLa cells. Contrary
      to a previous report, we found that the purified recombinant wild-type SipC(199
      409) protein is monomeric in solution by size exclusion chromatography coupled
      with multiangle laser light scattering assays (SEC-LS). Our data established that
      the actin nucleation activity of SipC plays a vital role in Salmonella-induced
      membrane ruffles and subsequent bacteria invasion.

PMID- 15720548
TI  - A che-like signal transduction cascade involved in controlling flagella
      biosynthesis in Rhodospirillum centenum.
AB  - Rhodospirillum centenum is a photosynthetic bacterium capable of undergoing swim
      cell to swarm cell differentiation that allows this species to be motile on both
      liquid and solid media. Previous experiments have demonstrated that the che1
      operon is required for the control of chemotactic and phototactic behaviour of
      both swim and swarm cells. In this report, we analyse the function of a second
      che-like gene cluster in R. centenum, the che2 gene cluster. In-frame deletion
      mutants of cheW2, cheB2, cheR2, cheY2, and of the entire che2 operon, exhibit
      defects in swim and swarm cell motility. Analysis of these strains demonstrates
      that they are non-motile, and that the non-motile phenotype is resulting from
      reduced polar and lateral flagella synthesis. Additionally, mutations in mcp2,
      ORF204, cheA2 and ORF74 remain chemotacticly and phototacticly competent at both
      high and low growth temperatures. Mutations in these che2 genes result in
      elevated levels of flagellin proteins giving rise to a hyperflagellate phenotype.
      We propose a model in which R. centenum utilizes a che-like signal transduction
      pathway (che2) for regulating flagellum synthesis in order to optimize swim cell
      swarm cell differentiation in response to changing environmental conditions.

PMID- 15720546
TI  - Pseudomonas aeruginosa fimL regulates multiple virulence functions by
      intersecting with Vfr-modulated pathways.
AB  - Virulence of Pseudomonas aeruginosa involves the co-ordinate expression of a
      range of factors including type IV pili (tfp), the type III secretion system
      (TTSS) and quorum sensing. Tfp are required for twitching motility, efficient
      biofilm formation, and for adhesion and type III secretion (TTS)-mediated damage
      to mammalian cells. We describe a novel gene (fimL) that is required for tfp
      biogenesis and function, for TTS and for normal biofilm development in P.
      aeruginosa. The predicted product of fimL is homologous to the N-terminal domain
      of ChpA, except that its putative histidine and threonine phosphotransfer sites
      have been replaced with glutamine. fimL mutants resemble vfr mutants in many
      aspects including increased autolysis, reduced levels of surface-assembled tfp
      and diminished production of type III secreted effectors. Expression of vfr in
      trans can complement fimL mutants. vfr transcription and production is reduced in
      fimL mutants whereas cAMP levels are unaffected. Deletion and insertion mutants
      of fimL frequently revert to wild-type phenotypes suggesting that an extragenic
      suppressor mutation is able to overcome the loss of fimL. vfr transcription and
      production, as well as cAMP levels, are elevated in these revertants, while
      Pseudomonas quinolone signal (PQS) production is reduced. These results suggest
      that the site(s) of spontaneous mutation is in a gene(s) which lies upstream of
      vfr transcription, cAMP, production, and PQS synthesis. Our studies indicate that
      Vfr and FimL are components of intersecting pathways that control twitching
      motility, TTSS and autolysis in P. aeruginosa.

PMID- 15720549
TI  - Changes in lipopolysaccharide structure induce the sigma(E)-dependent response of
      Escherichia coli.
AB  - The envelope of Escherichia coli is composed of an asymmetric lipid bilayer
      containing lipopolysaccharide, phospholipid and outer membrane proteins (OMPs).
      Physical and chemical stresses impact on the integrity of the outer membrane
      envelope and trigger the sigma(E)-dependent response, whereby E. coli activates
      the expression of genes that increase its capacity for folding OMPs and
      synthesizing lipopolysaccharide (LPS). While it has already been appreciated that
      misfolded OMPs induce the sigma(E) response, a role for LPS in activating this
      pathway was hitherto unknown. Here we show that ammonium metavandate (NH4VO3)
      induces multiple changes in E. coli LPS structure and activates the sigma(E)
      dependent response without altering OMP. One such NH4VO3-mediated LPS decoration,
      the CrcA/PagP-catalysed addition of palmitate to lipid A, appeared to be alone
      sufficient to activate transcription at sigma(E)-dependent promoters.
      Furthermore, reduced acylation of LPS, caused by htrB or msbB mutations, also
      resulted in a constitutive expression of the sigma(E) regulon above wild-type
      levels. Production of these aberrant outer membrane lipids did not noticeably
      affect the composition or the amount of OMPs. A model is proposed whereby
      structural intermediates of the LPS biosynthetic pathway or modified LPS
      molecules may function as signals that activate the sigma(E) response.

PMID- 15720550
TI  - Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy
      binding protein with the Duffy antigen/receptor for chemokines (DARC).
AB  - Plasmodium vivax is one of four Plasmodium species that cause human malaria. P.
      vivax and a related simian malaria parasite, Plasmodium knowlesi, invade
      erythrocytes by binding the Duffy antigen/receptor for chemokines (DARC) through
      their respective Duffy binding proteins. Here we show that tyrosines 30 and 41 of
      DARC are modified by addition of sulphate groups, and that the sulphated tyrosine
      41 is essential for association of the Duffy binding proteins of P. vivax (PvDBP)
      and P. knowlesi (PkDaBP) with DARC-expressing cells. These sulphated tyrosines
      also participate in the association of DARC with each of its four known chemokine
      ligands. Alteration of tyrosine 41 to phenylalanine interferes with MCP-1, RANTES
      and MGSA association with DARC, but not with that of IL8. In contrast, alteration
      of tyrosine 30 to phenylalanine interferes with the association of IL8 with DARC.
      A soluble sulphated amino-terminal domain of DARC, but not one modified to
      phenylalanine at residue 41, can be used to block the association of PvDBP and
      PkDaBP with red blood cells, with an IC50 of approximately 5 nM. These data are
      consistent with a role for tyrosine sulphation in the association of many or most
      chemokines with their receptors, and identify a key molecular determinant of
      erythrocyte invasion by P. vivax.

PMID- 15720551
TI  - Mapping binding residues in the Plasmodium vivax domain that binds Duffy antigen
      during red cell invasion.
AB  - Summary Plasmodium vivax depends on interaction with the Duffy antigen/receptor
      for chemokines (DARC) for invasion of human erythrocytes. The 140 kDa P. vivax
      Duffy-binding protein (PvDBP) mediates interaction with DARC. The receptor
      binding domain of PvDBP maps to its N-terminal, cysteine-rich region, region II
      (PvRII), which contains approximately 300 amino acid residues including 12
      conserved cysteines. Using surface plasmon resonance, we show that binding of
      PvRII to DARC is a high-affinity interaction with a binding constant (K(D)) of
      8.7 nM. The minimal binding domain of PvRII has been previously mapped to a
      central 170-amino-acid stretch that includes cysteines 5-8. Here, we have used
      site-directed mutagenesis and quantitative binding assays to map amino acid
      residues within PvRII that make contact with DARC. Of the seven alanine
      replacement mutations that had an effect on binding, five were mutations in
      hydrophobic residues suggesting that hydrophobic interactions play a major role
      in the interaction of PvDBP with DARC. Genetic diversity studies have shown that
      six of the seven binding residues identified in PvRII are conserved in P. vivax
      field isolates, which provides support for their role in interaction with DARC.

PMID- 15720552
TI  - CcpN (YqzB), a novel regulator for CcpA-independent catabolite repression of
      Bacillus subtilis gluconeogenic genes.
AB  - In Bacillus subtilis, the NADPH-dependent glyceraldehyde-3-phosphate
      dehydrogenase (GapB) and the phosphoenolpyruvate carboxykinase (PckA) enzymes are
      necessary for efficient gluconeogenesis from Krebs cycle intermediates. gapB and
      pckA transcription is repressed in the presence of glucose but not via CcpA, the
      major transcriptional regulator for catabolite repression in B. subtilis. A B.
      subtilis mini-Tn10 transposant library was screened for clones affected in
      catabolite repression of gapB. Inactivation of a previously unknown gene, yqzB
      (renamed ccpN for control catabolite protein of gluconeogenic genes), was found
      to relieve not only gapB but also pckA transcription from catabolite repression.
      Purified CcpN specifically bound to the gapB and pckA promoters. ccpN is co
      transcribed constitutively with another unknown gene, yqfL. A yqfL deletion
      lowers the level of gapB and pckA transcription threefold under both glycolytic
      and gluconeogenic conditions and a ccpN deletion is epistatic over a yqfL
      deletion. YqfL is thus a positive regulator of the expression of gapB and pckA,
      the effect of which is not influenced by the metabolic regime of the cell but
      appears to be mediated by CcpN. ccpN has homologues in many Firmicutes, but not
      all, while yqfL homologues are widely distributed in Eubacteria and also present
      in some plants. In all analysed bacterial genomes, ccpN and yqfL are physically
      linked together or to putative gluconeogenic genes. CcpN thus orchestrates a
      novel CcpA-independent mechanism for catabolite repression of gluconeogenic genes
      highly conserved in Firmicutes and appears as a functional analogue of FruR in
      Enterobacteria. The physiological significance of the regulation mediated via the
      three B. subtilis global transcription regulators, CcpA, CggR and CcpN, is
      discussed.

PMID- 15720553
TI  - Iron-regulated transcription and capsule formation in the fungal pathogen
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans is the leading cause of fungal meningitis in humans.
      Production of a polysaccharide capsule is a key virulence property for the fungus
      and capsule synthesis is regulated by iron levels. Given that iron acquisition is
      an important aspect of virulence for many pathogens, we employed serial analysis
      of gene expression (SAGE) to examine the transcriptome under iron-limiting and
      iron-replete conditions. Initially, we demonstrated by SAGE and Northern analysis
      that iron limitation results in an elevated transcript level for the CAP60 gene
      that is required for capsule production. We also identified genes encoding
      putative components for iron transport and homeostasis, including the FTR1 (iron
      permease) gene, with higher transcript levels in the low-iron condition. An FTR1
      disruption mutant grows more slowly than wild-type cells in low-iron medium, and
      shows delayed growth and altered capsule regulation in iron-replete medium. Iron
      deprivation also resulted in elevated SAGE tags for putative extracellular
      mannoproteins and the GPI8 gene encoding a glycosylphosphatidylinositol (GPI)
      transamidase. The GPI8 gene appears to be essential while disruption of the CIG1
      gene encoding a mannoprotein resulted in impaired growth in low-iron medium and
      altered capsule response to the iron-replete condition. Additionally, we found
      that iron-replete conditions led to elevated transcripts for genes for iron
      storage, nitrogen metabolism, glycolysis, mitochondrial function, lipid
      metabolism and calmodulin-calcineurin signalling. Overall, these studies provide
      the first view of the C. neoformans transcriptional response to different iron
      levels.

PMID- 15720554
TI  - Identification of amino acid residues of the Agrobacterium tumefaciens quorum
      sensing regulator TraR that are critical for positive control of transcription.
AB  - The LuxR-type quorum-sensing transcription factor TraR regulates replication and
      conjugal transfer of the tumour-inducing (Ti) plasmid in the plant pathogen
      Agrobacterium tumefaciens. TraR is a two-domain protein with an N-terminal domain
      that binds to the quorum-sensing signal N-3-oxooctanoyl- l-homoserine lactone
      (OOHL) and a C-terminal domain that binds to specific DNA sequences called tra
      boxes. TraR-OOHL complexes form homodimers that activate transcription of at
      least seven promoters on the Ti plasmid. At five promoters, a tra box overlaps
      the binding site of core RNA polymerase (class II promoters), while in the other
      two promoters, this site is located farther upstream (class I promoters). In this
      study, we performed saturating point mutagenesis of the surface residues of the
      TraR C-terminal domain. Each mutant was tested for proteolytic stability and
      transcription activity in vivo, and for DNA binding activity in vitro. Mutants of
      TraR with single substitutions at positions W184, V187, K189, E193Q, V197 and
      D217 have wild-type levels of accumulation and DNA binding, but are defective in
      transcription of both types of promoters. These residues constitute a patch on
      the surface of the DNA-binding domain. We propose that this patch is an
      activating region that recruits RNA polymerase to TraR-dependent promoters
      through direct contact. As residues of this patch are critical for activation at
      both a class I and a class II promoter, we predict that these residues may
      contact the C-terminal domain of the RNA polymerase alpha-subunit.

PMID- 15720555
TI  - The Ras and Rho GTPases genetically interact to co-ordinately regulate cell
      polarity during development in Penicillium marneffei.
AB  - Ras and Rho GTPases have been examined in a wide variety of eukaryotes and play
      varied and often overlapping roles in cell polarization and development. Studies
      in Saccharomyces cerevisiae and mammalian cells have defined some of the central
      activities of these GTPases. However, these paradigms do not explain the role of
      these proteins in all eukaryotes. Unlike yeast, but like more complex eukaryotes,
      filamentous fungi have Rac-like proteins in addition to Ras and Cdc42. To
      investigate the unique functions of these proteins and determine how they
      interact to co-ordinately regulate morphogenesis during growth and development we
      undertook a genetic analysis of GTPase function by generating double mutants of
      the Rho GTPases cflA and cflB and the newly isolated Ras GTPase rasA from the
      dimorphic pathogenic fungus, Penicillium marneffei. P. marneffei growth at 25
      degrees C is as multinucleate, septate, branched hyphae which are capable of
      undergoing asexual development (conidiation), while at 37 degrees C, uninucleate
      pathogenic yeast cells which divide by fission are produced. Here we show that
      RasA (Ras) acts upstream of CflA (Cdc42) to regulate germination of spores and
      polarized growth of both hyphal and yeast cells, while also exhibiting CflA
      independent activities. CflA (Cdc42) and CflB (Rac) co-ordinately control hyphal
      cell polarization despite also having unique roles in regulating conidial
      germination and polarized growth of yeast cells (CflA) and polarized growth of
      conidiophore cell types and hyphal branching (CflB).

PMID- 15720556
TI  - Protein-DNA interactions in the T4 dNTP synthetase complex dependent on gene 32
      single-stranded DNA-binding protein.
AB  - Our laboratory has reported data suggesting a role for T4 phage gene 32 single
      stranded DNA-binding protein in organizing a complex of deoxyribonucleotide
      synthesizing enzymes at the replication fork. In this article we examined the
      effects of gene 32 ablation on the association of these enzymes with DNA-protein
      complexes. These experiments showed several deoxyribonucleotide-synthesizing
      enzymes to be present in DNA-protein complexes, with some of these associations
      being dependent on gene 32 protein. To further understand the role of gp32, we
      created amber mutations at codons 24 and 204 of gene 32, which encodes a 301
      residue protein. We used the newly created mutants along with several
      experimental approaches--DNA-cellulose chromatography, immunoprecipitation,
      optical biosensor analysis and glutathione-S-transferase pulldowns--to identify
      relevant protein-protein and protein-DNA interactions. These experiments
      identified several proteins whose interactions with DNA depend on the presence of
      intact gp32, notably thymidylate synthase, dihydrofolate (DHF) reductase,
      ribonucleotide reductase (RNR) and Escherichia coli nucleoside diphosphate (NDP)
      kinase, and they also demonstrated direct associations between gp32 and RNR and
      NDP kinase, but not dCMP hydroxymethylase, deoxyribonucleoside monophosphate
      kinase, or DHF reductase. Taken together, the results support the hypothesis that
      the gene 32 protein helps to recruit enzymes of deoxyribonucleoside triphosphates
      synthesis to DNA replication sites.

PMID- 15720557
TI  - Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-binding
      recombinant polypeptide confers protection against infection by respiratory and
      urogenital pathogens.
AB  - The human-specific pathogens Neisseria meningitidis, N. gonorrhoea, Haemophilus
      influenzae and Moraxella catarrhalis share the property of targeting the
      carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs)
      expressed on human epithelia. CEACAMs are signalling receptors implicated in cell
      adhesion and regulation of several physiological functions. Their targeting by
      pathogens can lead to tissue invasion. Although the CEACAM-binding ligands of the
      bacteria are structurally diverse, they target a common site on the receptor. We
      have generated a recombinant polypeptide that blocks the interactions of the
      mucosal pathogens with human epithelial cells and antibodies against it inhibit
      M. catarrhalis interactions with the receptor. As such, it is a potential
      antimicrobial agent to prevent infection via a strategy unlikely to promote
      bacterial resistance and a vaccine candidate against M. catarrhalis. In addition,
      it could serve more widely as a novel research tool and as a potential
      therapeutic agent in CEACAM-based physiological disorders.

PMID- 15720558
TI  - Intracellular multiplication of Legionella pneumophila depends on host cell amino
      acid transporter SLC1A5.
AB  - The infectious agent of Legionnaires' disease, Legionella (L) pneumophila,
      multiplies intracellularly in eukaryotic cells. This study has been performed to
      explore the nutrient requirements of L. pneumophila during intracellular
      replication. In human monocytes, bacterial replication rate was reduced by 76% in
      defined medium lacking L-cysteine, L-glutamine or L-serine. SLC1A5 (hATB(0,+)), a
      neutral amino acid transporter, was upregulated in the host cells after infection
      with L. pneumophila. Inhibition of SLC1A5 by BCH, a competitive inhibitor of
      amino acid uptake as well as siRNA silencing of the slc1a5 gene blocked
      intracellular multiplication of L. pneumophila without compromising viability of
      host cells. These observations suggest that replication of L. pneumophila depends
      on the function of host cell SLC1A5.

PMID- 15720559
TI  - In vivo analysis of the roles of conserved aspartate and histidine residues
      within a complex response regulator.
AB  - RcaC is the founding member of a group of large response regulators with complex
      domain combinations containing at least two receiver domains, an OmpR-class
      winged helix-turn-helix DNA binding domain, and a histidine phosphotransfer (HPt)
      domain. Within its two receiver and HPt domains, RcaC contains consensus
      phosphorylation sites at aspartates 51, 576 and histidine 316. RcaC operates in
      the pathway regulating transcription of genes encoding components of
      photosynthetic light harvesting antenna to changes in light colour. We show that
      phycocyanin gene expression requires RcaC. RcaC contributes to light regulation
      of phycoerythrin genes, but is not part of the second light regulation pathway
      controlling these genes. Substitutions at aspartate 51 or histidine 316 severely
      impaired light responsiveness while substitutions at aspartate 576 had little
      effect. Complete loss of light regulation, measured by phycocyanin gene
      expression, only occurred in the triple mutant. We conclude that aspartate 51
      primarily controls light colour responsiveness and is regulated by histidine 316,
      and that these residues are likely phosphorylated in red light and
      dephosphorylated in green light. The carboxy-terminal receiver domain has a minor
      role in controlling this response. RcaC abundance is also light regulated and
      depends on aspartate 51 and histidine 316, but not aspartate 576.

PMID- 15720560
TI  - Comparative genome hybridization reveals widespread aneuploidy in Candida
      albicans laboratory strains.
AB  - Clinical strains of Candida albicans are highly tolerant of aneuploidies and
      other genome rearrangements. We have used comparative genome hybridization (CGH),
      in an array format, to analyse the copy number of over 6000 open reading frames
      (ORFs) in the genomic DNA of C. albicans laboratory strains carrying one (CAI-4)
      to three (BWP17) auxotrophies. We find that during disruption of the HIS1 locus
      all genes telomeric to HIS1 were deleted and telomeric repeats were added to a 9
      nt sequence within the transforming DNA. This deletion occurred in approximately
      10% of transformants analysed and was stably maintained through two additional
      rounds of transformation and counterselection of the transformation marker. In
      one example, the deletion was repaired, apparently via break-induced replication.
      Furthermore, all CAI-4 strains tested were trisomic for chromosome 2 although
      this trisomy appears to be unstable, as it is not detected in strains
      subsequently derived from CAI-4. Our data indicate CGH arrays can be used to
      detect monosomies and trisomies, to predict the sites of chromosome breaks, and
      to identify chromosomal aberrations that have not been detected with other
      approaches in C. albicans strains. Furthermore, they highlight the high level of
      genome instability in C. albicans laboratory strains exposed to the stress of
      transformation and counterselection on 5-fluoro-orotic acid.

PMID- 15720562
TI  - HspR is a global negative regulator of heat shock gene expression in Deinococcus
      radiodurans.
AB  - The HspR protein functions as a negative regulator of chaperone and protease gene
      expression in a diversity of bacteria. Here we have identified, cloned and
      deleted the Deinococcus radiodurans HspR homologue, DR0934. Delta hspR mutants
      exhibit moderate growth defects when shifted to mild heat shock temperatures, but
      are severely impaired for survival at 48 degrees C. Using quantitative reverse
      transcription polymerase chain reaction and global transcriptional analysis, we
      have identified 14 genes that are derepressed in the absence of stress in the
      delta hspR background, 11 of which encode predicted chaperones and proteases,
      including dnaKJgrpE, ftsH, lonB, hsp20 and clpB. Promoter mapping indicated that
      the transcription of these genes initiates from a promoter bearing a sigma70-type
      consensus, and that putative HspR binding sites (HAIR) were present in the 5'
      untranslated regions. Electrophoretic mobility shift assays indicated that HspR
      binds to these promoters at the HAIR site in vitro. These results strongly
      suggest that DR0934 encodes the HspR-like global negative regulator of D.
      radiodurans that directly represses chaperone and protease gene expression by
      binding to the HAIR site in close proximity to promoter regions.

PMID- 15720564
TI  - LmxMPK9, a mitogen-activated protein kinase homologue affects flagellar length in
      Leishmania mexicana.
AB  - Components of mitogen-activated signal transduction pathways have been shown to
      be involved in flagellum biogenesis and maintenance. A mitogen-activated protein
      kinase homologue, designated LmxMPK9 from Leishmania mexicana, has been recently
      identified in a homology screen and its mRNA found to be present in all life
      stages. Three different splice-addition sites were used for mRNA maturation in
      trans-splicing in the different life stages. However, here we show that LmxMPK9
      protein is exclusively found in the promastigote stage. Recombinant expression of
      LmxMPK9 in Escherichia coli and kinase assays revealed a temperature optimum at
      27 degrees C, the optimal growth temperature for L. mexicana promastigotes, and a
      preference for manganese to promote substrate phosphorylation of myelin basic
      protein. A deletion mutant for the single-copy gene revealed significantly
      elongated flagella, whereas overexpression led to a subpopulation with rather
      short to no flagella suggesting a role for LmxMPK9 in flagellar morphogenesis.

PMID- 15720561
TI  - Leishmania salvage and remodelling of host sphingolipids in amastigote survival
      and acidocalcisome biogenesis.
AB  - Sphingolipids (SLs) play essential roles in most eukaryotes, but in the
      trypanosomatid protozoan Leishmania major their functions differ significantly.
      Previously we showed that null mutants defective in de novo sphingoid base
      synthesis (spt2-) lacked SLs but grew well and retained lipid rafts while
      replicating as promastigotes in vitro. However, they experienced catastrophic
      defects in membrane trafficking on entry into stationary phase, and failed to
      differentiate to the infective metacyclic form. Here we showed this mutant
      retained the ability to enter macrophages silently and inhibit activation,
      although as expected most parasites were destroyed. However, in mouse infections,
      after a delay rapidly progressive lesions appeared, and purified amastigotes were
      fully virulent to macrophages and mice. Mass spectrometry of spt2- amastigote
      lipids revealed the presence of high levels of parasite-specific inositol
      phosphorylceramides (IPCs) not synthesized by the mammalian hosts. Inhibitor
      studies showed that salvage occurs at the level of complex SLs, suggesting that
      parasites carry out 'headgroup' remodelling. Additionally, we describe a new
      defect of the spt2- promastigotes involving 'empty' acidocalcisomes (ACs), which
      may point to the origin of this organelle from the lysosome-related
      organelle/multivesicular body biogenesis pathway. However, ACs in spt2-
      amastigotes appeared quantitatively and morphologically normal. Thus salvage of
      SLs and other molecules by intracellular amastigotes play key roles in AC
      biogenesis and parasite survival in the host.

PMID- 15720563
TI  - Differential binding specificities of oral streptococcal antigen I/II family
      adhesins for human or bacterial ligands.
AB  - The antigen I/II (AgI/II) family polypeptides, ranging from 1310 to 1653 amino
      acid (aa) residues, are cell wall anchored adhesins expressed by most indigenous
      species of oral streptococci. The polypeptides interact with a wide range of host
      molecules, in particular salivary agglutinin glycoprotein (SAG or gp340), and
      with ligands on other oral bacteria. To determine the receptor recognition
      properties of six different AgI/II family polypeptides from strains of
      Streptococcus gordonii, Streptococcus intermedius and Streptococcus mutans, the
      genes were cloned and expressed on the surface of the surrogate host Lactococcus
      lactis. The S. gordonii SspA and SspB polypeptides mediated higher binding levels
      of L. lactis cells to surface immobilized gp340 than did S. intermedius Pas
      protein, or S. mutans SpaP or PAc proteins. However, the AgI/II proteins were all
      similar in their abilities to mediate aggregation of lactococci by fluid phase
      gp340. The SpaP(I) polypeptide from S. mutans Ingbritt, which was C-terminally
      truncated by approximately 400 aa residues, did not bind gp340. Lactococci
      expressing AgI/II proteins, including SpaP(I), were aggregated by a synthetic 16
      aa residue peptide SRCRP2 derived from the aa repeat block sequences within
      gp340. In coaggregation assays, SspB from S. gordonii was unique in mediating
      coaggregation with only group A and group E strains of Actinomyces naeslundii.
      All the other AgI/II polypeptides mediated coaggregation with group C and group D
      strains of A. naeslundii. Analysis of chimeric protein constructs revealed that
      coaggregation specificity was determined by sequences within the N-terminal half
      of AgI/II protein. A synthetic peptide (20 aa residues), which defines a putative
      adhesion epitope within the C-terminal region of polypeptide, inhibited AgI/II
      mediated aggregation by gp340 but did not affect coaggregation with A.
      naeslundii. These results suggest that different mechanisms operate in
      interactions of AgI/II family polypeptides with native gp340, gp340 SRCR domain
      peptide, and A. naeslundii. Specificity of these interactions appears to be
      determined by discontinuous but interacting regions of the polypeptides, thus
      providing flexibility in receptor recognition for streptococcal colonization of
      the human host.

PMID- 15720565
TI  - Isolation and characterization of aminopeptidase from Capnocytophaga granulosa
      ATCC 51502.
AB  - There is evidence that enzymes from the genus Capnocytophaga play a role in
      dental calculus formation. Although most of the species in the genus produce
      aminopeptidases, there is a paucity of data on the purification and
      characterization of the enzyme, except in the case of Capnocytophaga gingivalis.
      The aim of this study was to purify aminopeptidase from culture supernatant of
      Capnocytophaga granulosa ATCC 51502, a new species of the genus. Purification was
      performed using ammonium sulfate fractionation and two chromatographic steps. The
      aminopeptidase was purified 158,433-fold with a yield of 12.0%. The enzyme
      appeared to be a trimer with a molecular mass of 270 kDa. The optimal pH of the
      aminopeptidase was 6.5 and its activity was completely inhibited by incubation at
      50 degrees C for 10 min. The enzyme showed maximum specificity for basic amino
      acids (Arg and Lys) and also hydrolyzed noncharged amino acids (Met, Leu and
      Ala). Ca(2+), Zn(2+) and Fe(3+) activated the enzyme, while EDTA, Ag(+), Hg(+)
      and Cu(2+) inhibited it. These results suggest that aminopeptidase of C.
      granulosa is different from that of C. gingivalis but similar to aminopeptidase
      B.

PMID- 15720566
TI  - Low salivary IgA activity to cell-surface antigens of mutans streptococci related
      to HLA-DRB1*04.
AB  - BACKGROUND/AIMS: Mutans streptococci are found in almost all individuals, though
      there are large differences in colonization levels between individuals. These
      differences are not readily explained, though several factors are believed to
      influence the colonization. One factor is the immune response to mutans
      streptococci, mainly provided by salivary immunoglobulin A (IgA). In a previous
      study, differences in salivary IgA reactions to oral streptococci were observed
      between human leukocyte antigen (HLA)-DR4-positive and DR4-negative individuals.
      A lower salivary IgA activity to Streptococcus mutans in particular was most
      pronounced for two DR4 subgroups, DRB1*0401 and *0404. The main purpose of this
      study was to further investigate, in a larger study group, the salivary IgA
      activity to antigens of three oral streptococci in relation to different HLA
      DRB1*04 alleles. METHODS: Stimulated saliva was collected from 58 HLA-DRB1*04
      positive individuals. Whole cell antigen extracts from S. mutans, Streptococcus
      sobrinus and Streptococcus parasanguis and the streptococcal antigen (SA) I/II
      were separated in SDS-PAGE, transblotted and detected with diluted saliva
      (Western blot), and analyzed in a computer program. All distinct immunoblot bands
      over 100 kDa were recorded and compared in relation to DRB1*04. RESULTS: The
      immunoblots revealed lower salivary IgA reactions to S. mutans, S. sobrinus and
      SA I/II, but not to S. parasanguis, for the DRB1*0401- and *0404-positive
      individuals compared to other DRB1*04 types. For the *0401 subgroup there was a
      significant association with a lower IgA response to S. mutans. CONCLUSION: The
      results confirm earlier observations and may also support previous demonstrated
      association between colonization by mutans streptococci and the serologically
      defined HLA-DR4.

PMID- 15720568
TI  - Relationship between Candida infection and immune cellular response in
      inflammatory hyperplasia.
AB  - OBJECTIVES: To analyze and quantify the CD8(+) and CD4(+) T-lymphocyte
      populations in inflammatory hyperplasia and to establish the relationship between
      the frequency and location of these cells and Candida infection. METHODS: Samples
      of inflammatory hyperplasia were stained with PAS for evidence of Candida sp. and
      were classified in two groups, infected and control, according to the presence or
      absence of infection. After immunoreaction with specific anti-CD4 and anti-CD8
      monoclonal antibodies, the distribution and frequency of the positive cells were
      analyzed in 41 cases (19 controls without Candida sp. and 22 infected cases).
      Lymphocytes were quantified in the three consecutive fields where the
      inflammatory infiltration was concentrated. RESULTS: There was no relationship
      between the frequency and location of CD4(+) T cells and Candida sp. infection.
      The number of CD8(+) cells close to the fungi hyphae as well as the total number
      of CD8(+) T cells present in inflammatory hyperplasia were higher in the Candida
      sp. group than in the control noninfected group (P < 0.05). CONCLUSION: Since the
      CD8(+) T cells were distributed according to the location of Candida sp. hyphae,
      and since a higher CD8(+)/total lymphocytes ratio was observed in the infected
      group, we suggest a role for CD8(+) T cells in the defense against Candida in
      oral infections associated with inflammatory hyperplasia in immunocompetent
      individuals.

PMID- 15720567
TI  - Effects of Porphyromonas gingivalis antigens and proinflammatory cytokines on
      human coronary artery endothelial cells.
AB  - OBJECTIVE: Individuals with periodontitis have been cited as having a
      significantly increased risk of developing coronary heart disease. Although
      accumulating evidence suggests that periodontal infection is involved in the
      development and progression of atherosclerosis, the underlying mechanisms remain
      to be elucidated. In the present study, we examined how periodontal infection
      could contribute to endothelial dysfunction. METHODS: Human coronary arterial
      endothelial cells were stimulated with tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-1beta, both of which are reported to be elevated in the serum of
      periodontitis patients. Cells were also stimulated with lipopolysaccharide, outer
      membrane protein and heat shock protein 60 derived from Porphyromonas gingivalis,
      a representative periodontopathic bacterium which is known to stimulate myeloid
      cells. RESULTS: Although TNF-alpha and IL-1beta, at concentrations a little
      higher than those in sera of periodontitis patients, up-regulated the expression
      of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, P.
      gingivalis antigens had only a slight stimulatory effect. CONCLUSION: Experiments
      in which the total pathogen burden is considered, rather than a single species of
      bacteria, would increase our understanding of the contribution of which
      periodontal infection to atherogenesis.

PMID- 15720569
TI  - Antimicrobial actions of benzimidazoles against oral streptococci.
AB  - BACKGROUND/AIM: Benzimidazoles, such as lansoprazole and omeprazole, are used
      extensively as proton-pump inhibitors to control stomach acid secretion and also
      have antimicrobial actions against Helicobacter pylori. Our objective was to
      determine whether they are potentially useful antimicrobials against oral
      bacteria. METHODS: Streptococcus mutans was our main test organism. It was grown
      in suspension cultures and biofilms. Standard physiologic assays were used to
      assess inhibitory actions of benzimidazoles. RESULTS: Benzimidazoles inhibited
      acid production by S. mutans in suspensions or biofilms. In pH-drop experiments,
      lansoprazole at a level of only 0.025 mm irreversibly inhibited acid production
      from glycolysis. Cell uptake of lansoprazole was found to be very pH sensitive
      and occurred mainly at pH values below about 5, indicating that the protonated
      form was taken up. Lansoprazole inhibition of glycolysis could be blocked by 2
      mercaptoethanol, which suggests that disulfide bonds form between benzimidazoles
      and protein targets. Identified targets for benzimidazole inhibition included the
      phosphoenolpyruvate : sugar phosphotransferase system, the glycolytic enzymes
      aldolase, glyceraldehyde-3-phosphate dehydrogenase, and lactic dehydrogenase, and
      enzymes such as urease and arginine deiminase. Lansoprazole increased proton
      permeabilities of S. mutans cells but did not inhibit F-ATPases. Although cells
      in biofilms were somewhat less sensitive to the agents than those in suspensions,
      biofilm glycolysis was still markedly inhibited by 0.1 mm lansoprazole.
      Benzimidazoles are bactericidal, and the oral anaerobes Fusobacterium nucleatum
      and Prevotella intermedia were more sensitive to killing than was S. mutans.
      CONCLUSION: Benzimidazoles appear to be useful inhibitors of oral bacteria in
      acid environments such as progressing caries lesions.

PMID- 15720570
TI  - Antimicrobial activity of Croton cajucara Benth linalool-rich essential oil on
      artificial biofilms and planktonic microorganisms.
AB  - We have previously demonstrated that a linalool-rich essential oil from Croton
      cajucara Benth presents leishmanicidal activity. In the present study, we
      demonstrate that this essential oil inhibits the growth of reference samples of
      Candida albicans, Lactobacillus casei, Staphylococcus aureus, Streptococcus
      sobrinus, Porphyromonas gingivalis and Streptococcus mutans cell suspensions, all
      of them associated with oral cavity disease. The purified linalool fraction was
      only inhibitory for C. albicans. Microbes of saliva specimens from human
      individuals with fixed orthodontic appliances, as well as the reference strains,
      were used to construct an artificial biofilm which was exposed to linalool or to
      the essential oil. As in microbial suspensions, the essential oil was toxic for
      all the microorganisms, while the purified linalool fraction mainly inhibited the
      growth of C. albicans. The compounds of the essential oil were separated by thin
      layer chromatography and exposed to the above-cited microorganisms. In this
      analysis, the proliferation of the bacterial cells was inhibited by still
      uncharacterized molecules, and linalool was confirmed as the antifungal component
      of the essential oil. The effects of linalool on the cell biology of C. albicans
      were evaluated by electron microscopy, which showed that linalool induced a
      reduction in cell size and abnormal germination. Neither the crude essential oil
      nor the purified linalool fraction is toxic to mammalian cells, which suggests
      that the essential oil or its purified components may be useful to control the
      microbial population in patients with fixed orthodontic appliances.

PMID- 15720572
TI  - Role of helper T cells in the humoral immune responses against 53-kDa outer
      membrane protein from Porphyromonas gingivalis.
AB  - Outer membrane protein with a 53-kDa molecular weight (Ag53) isolated from
      Porphyromonas gingivalis evokes strong humoral immune responses in many
      periodontitis patients. To examine the effects of cytokines produced by Ag53
      specific Th cells on the IgG production against Ag53, we established Ag53
      specific Th-cell lines from patients with early onset periodontitis and from
      healthy volunteers. We then developed a mixed lymphocyte culture system between
      Ag53-specific Th cells and auto- or allo-derived T-cell-depleted leukocytes
      produced from the subjects whose HLA class II haplotypes were completely matched.
      Interferon-gamma production was observed in all Th cell lines from patients and
      healthy subjects. As for Th2 type cytokines, interleukin (IL)-4, IL-5, IL-6 and
      IL-10 production varied greatly in Th cells regardless of the periodontal
      condition of the donor. Only Th cell lines with a high Th2/Th1 ratio induced Ag53
      specific IgG production when cocultured with T-cell-depleted leukocytes. Thus,
      the difference in Th2/Th1 balance may regulate the Ag53-specific IgG production.

PMID- 15720571
TI  - Study of anticandidal activity of carvacrol and eugenol in vitro and in vivo.
AB  - BACKGROUND/AIMS: The mechanism of the anticandidal action of the major phenolic
      components of oregano and clove essential oils - carvacrol and eugenol - was
      studied. This activity was also evaluated for the therapeutic efficacy in the
      treatment of the experimental oral candidiasis induced by Candida albicans in
      immunosuppressed rats. METHODS: In vitro, the addition of carvacrol at 0.1% or
      eugenol at 0.2% during the exponential growth of C. albicans was evaluated. The
      release of substances absorbing at 280 nm by cells treated with these two
      components was also measured spectrophotometrically. In vivo, oral candidiasis in
      immunosuppressed rats was established by inoculating 3 x 10(8) cells of C.
      albicans with a cotton swab on three alternate days. The number of colony counts
      was evaluated from the oral cavity of rats treated for eight consecutive days
      with carvacrol, eugenol or nystatin and compared to untreated controls. RESULTS:
      Carvacrol and eugenol were fungicidal in exponentially growing C. albicans.
      Interestingly, this fungicidal effect was accompanied by the release of
      substances absorbing at 280 nm. In an immunosuppressed rat model of oral
      candidiasis, carvacrol or eugenol treatment significantly (P < 0.05) reduced the
      number of colony counts sampled from the oral cavity of rats treated for eight
      consecutive days compared to untreated control rats. Similar results were
      obtained with nystatin used as a reference treatment. CONCLUSION: The in vitro
      results indicated that both carvacrol and eugenol exerted an anticandidal effect
      by a mechanism implicating an important envelope damage. Their in vivo efficacy
      on experimental oral candidiasis leads us to consider them as possible antifungal
      agents.

PMID- 15720573
TI  - Binding of Actinobacillus actinomycetemcomitans lipopolysaccharides to
      Peptostreptococcus micros stimulates tumor necrosis factor alpha production by
      macrophage-like cells.
AB  - Peptostreptococcus micros is a gram-positive bacterium that has been associated
      with periodontitis and endodontic infections. In this study, we hypothesized that
      P. micros binds the immunomodulating component lipopolysaccharide derived from
      gram-negative bacteria to increase its capacity to stimulate cytokine production
      by host cells. The ability of P. micros to bind Actinobacillus
      actinomycetemcomitans lipopolysaccharide was demonstrated by an enzyme-linked
      immunosorbent assay and by immunoelectron microscopy. Pretreatment of P. micros
      cells with A. actinomycetemcomitans lipopolysaccharide was associated with a 49
      fold increase in tumor necrosis factor alpha production by human monocytic cells
      U937 differentiated into adherent macrophages, compared to the stimulation with
      untreated P. micros. This effect was suppressed by incorporating polymyxin B, a
      lipid A-binding substance, during treatment of macrophage-like cells with
      lipopolysaccharide-coated P. micros cells. This is the first study reporting a
      binding interaction between lipopolysaccharide and a gram-positive bacterium.
      This interaction represents a new mechanism that could promote the inflammatory
      response during periodontitis.

PMID- 15720574
TI  - Mutational analysis of the adcCBA genes in Streptococcus gordonii biofilm
      formation.
AB  - Streptococcus gordonii, a primary colonizer, is part of the pioneer biofilm
      consortium that initiates dental plaque development on tooth surfaces. An
      insertion of Tn917-lac transposon into the adcR gene produced a biofilm-defective
      phenotype. S. gordonii adcR is a regulatory gene and is part of an operon (adc)
      that includes three other genes, adcCBA. AdcC contains a putative consensus
      binding site for adenosine triphosphate, AdcB is a putative hydrophobic membrane
      protein, and AdcA is a putative lipoprotein permease. Mutants were constructed by
      insertional inactivation in each of the three adcCBA genes and their effects on
      biofilm formation examined. The adcC::spec(R) and adcB::spec(R) mutations
      displayed a biofilm-defective phenotype, whereas the adcA::spec(R) mutant was
      biofilm-positive in a static polystyrene microtiter plate biofilm assay. All
      three mutants formed poor biofilms in a flow-cell system and were competence
      defective, suggesting the adc operon plays an important role in S. gordonii
      biofilm formation and competence.

PMID- 15720576
TI  - Committee report: Guidelines for human startle eyeblink electromyographic
      studies.
AB  - The human startle response is a sensitive, noninvasive measure of central nervous
      system activity that is currently used in a wide variety of research and clinical
      settings. In this article, we raise methodological issues and present
      recommendations for optimal methods of startle blink electromyographic (EMG)
      response elicitation, recording, quantification, and reporting. It is hoped that
      this report will foster more methodological validity and reliability in research
      using the startle response, as well as increase the detail with which relevant
      methodology is reported in publications using this measure.

PMID- 15720575
TI  - Impact of sample storage on detection of periodontal bacteria.
AB  - BACKGROUND/AIMS: Information on the impact of sample storage prior to analysis by
      DNA methods is limited. The aim of this study was to investigate the effect of
      subgingival sample storage on bacterial detection and enumeration. MATERIAL AND
      METHODS: Subgingival plaque samples were studied by a) checkerboard DNA-DNA
      hybridization by immediate processing, b) storage at + 4 degrees C for 6 weeks,
      c) storage at - 20 degrees C for 6 months or d) storage at - 20 degrees C for 12
      months. RESULTS: No differences in total DNA were found between protocol 1 and 2,
      or between protocol 3 and 4. Protocol 1 yielded 2.4 times more total bacterial
      DNA than did protocol 3 (P < 0.001). Actinobacillus actinomycetemcomitans and
      Campylobacter gracilis were detected in 21.1% of the immediately processed
      samples but only in 6.6% of the samples after 12 months of storage. Similar
      changes were noticed for Treponema denticola, which was detected in 22.3% and
      9.2%, respectively. Streptococci spp., Fusobacterium nucleatum and Tannerella
      forsythia did not seem to be affected by storage. In contrast, the level of
      Campylobacter rectus detection frequency changed from 2.6% if processed
      immediately to 15.8% if samples were stored for 12 months. CONCLUSIONS: In
      longitudinal clinical studies including microbiological samples and processed
      with DNA-DNA hybridization methods, samples should be stored for the same period
      of time before processing to avoid loss of microbiological information.

PMID- 15720577
TI  - EOG correction: a comparison of four methods.
AB  - EOG correction is a class of techniques that account for ocular artifact in the
      electroencephalogram (EEG) by subtracting electrooculographic data from the EEG.
      The purpose of this study was to evaluate four of these correction techniques
      (Verleger, Gasser, & Mocks, 1982 [VGM]; Gratton, Coles, & Donchin, 1983 [GCD];
      Semlitsch, Presslich, Schuster, & Anderer, 1986 [SPSA]; Croft & Barry, 2000
      [CB]). Blinks, vertical eye movements (VEM), and horizontal eye movements (HEM)
      from 26 subjects were corrected using these techniques, and eye movement event
      related potentials computed to aid validation. HEMs were corrected better by CB,
      VGM/GCD then SPSA, VEMs by CB, VGM/GCD then SPSA, and blinks by CB, SPSA, GCD and
      then VGM, with the advantage of CB substantial for blinks (eta2>.72), VEMs
      (eta2>.60), and HEMs (eta2>.27). It is argued that the CB procedure adequately
      accounts for ocular artifact in the EEG. Reasons for the limitations of the other
      procedures are discussed.

PMID- 15720578
TI  - Memory-based or afferent processes in mismatch negativity (MMN): a review of the
      evidence.
AB  - The mismatch negativity (MMN) is an electromagnetic response to any discriminable
      change in regular auditory input. This response is usually interpreted as being
      generated by an automatic cortical change-detection process in which a difference
      is found between the current input and the representation of the regular aspects
      of the preceding auditory input. Recently, this interpretation was questioned by
      Jaaskelainen et al. (2004) who proposed that the MMN is a product of an N1 (N1a)
      difference wave emerging in the subtraction procedure used to visualize and
      quantify the MMN. We now evaluate this "adaptation hypothesis" of the MMN in the
      light of the available data. It is shown that the MMN cannot be accounted for by
      differential activation of the afferent N1 transient detectors by repetitive
      ("standard") stimuli and deviant ("novel") stimuli and that the presence of a
      memory representation of the standard is required for the elicitation of MMN.

PMID- 15720579
TI  - Strategic control and medial frontal negativity: beyond errors and response
      conflict.
AB  - Errors in timed choice tasks typically produce an error-related negativity (ERN)
      in the event-related potential (ERP). The error specificity of the ERN has been
      challenged by studies showing a correct response negativity (CRN). Forty-five
      participants engaged in a flanker task in which both compatibility between
      flankers and target and the probability of compatible flankers were manipulated.
      Correct responses elicited a CRN, the amplitude of which increased with the
      degree of mismatch between the presence of conflict and conflict probability,
      even on low-conflict (compatible) trials. The fronto-central N2 component was
      larger on high-conflict (incompatible) correct response trials. However, in
      contrast to some recent accounts, this N2 was largest for highly probable
      stimuli. These findings suggest revision to models of the effects of conflict on
      response-related negativity to account for strategic adjustments made in
      preparation for the response.

PMID- 15720580
TI  - ERP correlates of involuntary attention capture by prosodic salience in speech.
AB  - This study addressed whether temporally salient (e.g., word onset) or
      prosodically salient (e.g., stressed syllables) information serves as a cue to
      capture attention in speech sound analysis. In an auditory oddball paradigm, 16
      native English speakers were asked to ignore binaurally presented disyllabic
      speech sounds and watch a silent movie while ERPs were recorded. Four types of
      phonetic deviants were employed: a deviant syllable that was either stressed or
      unstressed and that occurred in either the first or second temporal position. The
      nature of the phonetic change (a change from a voiced consonant to its
      corresponding unvoiced consonant) was kept constant. MMNs were observed for all
      deviants. In contrast, the P3a was only seen when the deviance occurred on
      stressed syllables. The sensitivity of the P3a to the stress manipulation
      suggests that prosodic rather than temporal salience captures attention in
      unattended speech sounds.

PMID- 15720582
TI  - Electrophysiological correlates of error correction.
AB  - Evidence in the literature for the proposed relationship between the error
      related negativity (ERN) and error correction is rather limited and inconsistent.
      We investigated corrective behavior and the ERN in two groups of participants who
      performed a flanker task. The correction-instructed group was asked to
      immediately correct all encountered errors. The noninstructed group was unaware
      that corrective responses were recorded. We found a negative deflection following
      corrected errors that peaked at 200-240 ms after the error. We refer to this
      negativity in the ERP waveform as correction-related negativity (CoRN). We assume
      that the correction-related negativity reflects evaluative functions of the motor
      system necessary for error corrections. ERN latency and amplitude were modulated
      by the occurrence and temporal characteristics of immediate corrections. These
      results are discussed within the framework of current models of performance
      monitoring.

PMID- 15720581
TI  - Event-related potential correlates of task switching and switch costs.
AB  - Studies of task switching demonstrate that task switches are associated with
      response costs and that these costs are reduced when a cue is presented in
      advance of a switch. The present study examined cortical event-related potential
      correlates of task switching and switch costs in 39 participants during a cued
      match/mismatch discrimination task. Compared with non-switch trials, switch
      trials were associated with a larger cue-related, anticipatory P3b-like waveform.
      Switch trials were also associated with smaller target-related, stimulus
      dependent P2 and P3-like components. Moreover, the switch-related amplitude
      variability in the P3b to the cue and the P2 to the target were associated with
      unique components of the residual switch costs. The results support an integrated
      model of task switching with complementary yet distinct roles for anticipatory
      and stimulus-dependent processes in task switching and switch costs.

PMID- 15720583
TI  - Nociception and baroreceptor stimulation in hypertension-prone men and women.
AB  - We examined the effects of baroreceptor stimulation on nociceptive responding in
      men and women with a positive or negative parental history of hypertension. The
      effects of three baroreceptor conditions (stimulation, inhibition, and control)
      on subjective pain and nociceptive responding were evaluated during
      electrocutaneous sural nerve stimulation. Pain ratings were lower in men with
      positive parental history relative to men with negative parental history, but
      this difference was not found in women. Both stimulatory and inhibitory
      baroreceptor conditions were associated with reduced pain reports compared to the
      control condition. There were no significant differences in nociceptive
      responding as a function of parental history of hypertension. Although this study
      confirms a link between hypoalgesia and risk for hypertension in men, it does not
      support the hypothesis that this attenuated pain perception is due to enhanced
      baroreceptor activity.

PMID- 15720584
TI  - Emotions and airway resistance in asthma: study with whole body plethysmography.
AB  - The role of emotions as potential triggers of asthmatic airway obstructions was
      examined by whole body plethysmography. Three affectively homogeneous picture
      series (IAPS) were presented with video glasses to induce pleasant, unpleasant,
      and neutral emotional states in 32 asthmatic and 32 nonasthmatic participants
      while they were seated in a Jaeger Bodytest plethysmograph. Airway resistance,
      specific airway resistance, thoracic gas volume, and mood were measured
      immediately after each presentation, in addition to specific airway resistance
      before and during each presentation. Airway resistance and specific airway
      resistance were significantly increased after and during pleasant and unpleasant
      stimulation compared to neutral stimulation in asthmatic patients and also, but
      less pronounced, in nonasthmatic controls. The results show that the experience
      of pleasant and unpleasant emotions can provoke increased airway resistance
      especially in asthmatic patients.

PMID- 15720585
TI  - The influence of hydration status on stress-induced hemoconcentration.
AB  - This study examined the effects of hydration status on rheological and
      hemodynamic activity during rest, mental stress, postural stress, and combined
      mental/postural stress in 24 men when euhydrated and hyperhydrated. The stress
      tasks elicited hemoconcentration, although the effects were less pronounced
      during mental stress. Hyperhydration was associated with higher plasma volume
      throughout. All stress tasks also perturbed hemodynamic activity, irrespective of
      hydration status, with the exception of heart rate reactivity, which was
      attenuated when hyperhydrated. As expected the combined stress during euhydration
      was associated with an unfavorable rheological and cardiovascular profile, which
      may help explain the increased incidence of cardiovascular events in the morning.

PMID- 15720586
TI  - A comparison of psychophysiological and self-report measures of BAS and BIS
      activation.
AB  - The behavioral approach (BAS) and behavioral inhibition (BIS) systems are central
      to theories of both personality and psychopathology, yet agreement on methods of
      assessing BAS and BIS sensitivity has yet to emerge. We compare the Carver and
      White (1994) BIS/BAS scales with putative physiological markers of BAS (pre
      ejection period [PEP], respiratory sinus arrhythmia [RSA]) and BIS (electrodermal
      responding) reactivity during reward and extinction among 50 undergraduates. PEP,
      RSA, and electrodermal activity each responded strongly to one or more task
      conditions, but correlations with BIS/BAS scores were stronger for measures of
      affectivity than for any physiological marker. Finally, PEP reactivity was the
      only autonomic index that responded only to reward. These findings suggest that
      (a) self-report and physiological measures of BAS and BIS reactivity are
      independent, and (b) PEP may be superior to RSA as an index of approach
      motivation.

PMID- 15720587
TI  - The relationship between women's subjective and physiological sexual arousal.
AB  - Previous literature presents discordant results on the relationship between
      physiological and subjective sexual arousal in women. In this study, the use of
      hierarchical linear modeling (HLM) revealed a significant concordance between
      continuous measures of physiological and subjective sexual arousal as assessed
      during exposure to erotic stimuli in a laboratory setting. We propose that past
      studies that have found little or no association between the two measures may
      have been in part limited by the methodology and statistical analyses employed.

PMID- 15720588
TI  - Cardiovascular reactivity and family history of hypertension: a meta-analysis.
AB  - A regression-based meta-analysis examined the degree to which the effects of a
      family history of hypertension on cardiovascular reactivity are moderated by the
      magnitude of cardiovascular responses elicited in challenge/task conditions. Mean
      change scores for negative family history groups were regressed on mean change
      scores for positive family history groups. The slopes of separate regression
      lines obtained for systolic and diastolic blood pressure and heart rate were
      significantly less than 1.0 and the y-intercepts for these regression lines were
      significantly greater than zero. This pattern indicates that family history
      differences in cardiovascular reactivity to stress are greatest in situations
      that elicit the smallest baseline-stressor change scores in non-family-history
      groups.

PMID- 15720589
TI  - Splenic torsion in an alpaca.
AB  - OBJECTIVE: To describe the clinical signs, diagnostic evaluation and surgical
      management of an alpaca with splenic torsion. ANIMALS: Six-year-old female
      alpaca. RESULTS: Splenic torsion and uterine torsion were the inciting cause for
      persistent abdominal discomfort in this alpaca. Rectal examination,
      abdominocentesis, and transabdominal ultrasonographic findings were suggestive of
      a splenic lesion. Surgical management involved splenectomy of a necrotized
      spleen. CONCLUSIONS: Although rare in occurrence, splenic torsion should be
      considered as a potential cause of abdominal discomfort in alpacas. Splenectomy
      is a reasonable and successful method of treatment for a devitalized spleen
      secondary to splenic torsion in alpacas. CLINICAL RELEVANCE: Splenic torsion
      causes persistent abdominal discomfort in camelids and may be associated with
      uterine torsion. Rectal examination, transabdominal ultrasound and
      abdominocentesis are useful diagnostic tools to differentiate splenic torsion
      from other causes of abdominal discomfort. Splenectomy is an uncomplicated
      procedure in camelids and has a favorable prognosis.

PMID- 15720590
TI  - Sternothyroideus myotomy, staphylectomy, and oral caudal soft palate
      photothermoplasty for treatment of dorsal displacement of the soft palate in 102
      thoroughbred racehorses.
AB  - OBJECTIVE: To compare racing performance before and after sternothyroideus
      myotomy, staphylectomy, and oral caudal soft palate photothermoplasty in
      Thoroughbred racehorses with intermittent dorsal displacement of the soft palate
      (DDSP). STUDY DESIGN: Retrospective study. ANIMALS: Thoroughbred racehorses
      (n=102) with DDSP. METHODS: Retrieved data included signalment, primary
      complaint, and upper respiratory tract endoscopic finding. Lifetime race records
      were compared for earnings per start before and after surgery, days to 1st start,
      and races won postoperatively. RESULTS: Comparing mean earnings per start for 3
      races before (2792 dollars) and after (3806 dollars) surgery, racing performance
      improved significantly after surgery in 63% (46/73) of horses that competed in at
      least 1 race before and after surgery (P=.02). Mean and median days to 1st start
      after surgery were 109 and 69 days, respectively. Of horses that raced
      postoperatively 65% (60/92) won at least 1 race, and 77% (71/92) raced in >5
      races after surgery. CONCLUSIONS: Sternothyroideus myotomy, staphylectomy, and
      oral caudal soft palate photothermoplasty significantly improved racing
      performance in experienced Thoroughbred racehorses with performance limiting
      DDSP, and overall had a similar outcome to other reported surgical techniques for
      treatment of DDSP. Clinical Relevance-Sternothyroideus myotomy, staphylectomy,
      and oral caudal soft palate photothermoplasty should be considered as a surgical
      approach to correction of DDSP in Thoroughbred racehorses; however, it is
      possible that staphylectomy may not be necessary to achieve a desirable outcome.

PMID- 15720591
TI  - Repair of radial fractures in toy breed dogs with self-reinforced biodegradable
      bone plates, metal screws, and light-weight external coaptation.
AB  - OBJECTIVE: To describe a surgical technique for, and outcome after, treatment of
      radial fractures with biodegradable self-reinforced polylactide plates and metal
      screws, and external coaptation. STUDY DESIGN: Prospective clinical study. SAMPLE
      POPULATION: Eleven Toy breed dogs. METHODS: Radial fractures were repaired by
      application of a single or 2 stacked biodegradable self-reinforced polylactide
      plates (poly-L/D, L-lactide, stereocopolymer [LL-and DL-lactide ratio 70/30]; SR
      PLA (70/30) implants) secured with metal screws, and light-weight external
      coaptation. Healing was evaluated clinically and by radiography at 2, 4, 6, 8, 9,
      12, 24-26 weeks, and at 1 and 2 years. Owners were interviewed 3 years after
      surgery. RESULTS: Radial fracture lines disappeared within 4-14 weeks in 10 dogs;
      an implant failed in 1 dog. Ambulation was excellent for healed fractures.
      Excessive skin tension led to removal of implants in 1 dog and suture repair in
      another dog. No foreign body reaction from implant degradation was observed and
      the plate was usually no longer palpable at 2 years. One dog had a fracture
      through a screw hole at 1 year. CONCLUSION: Healing and complication rates after
      repair of radial fractures with SR-PLA (70/30) plates were considered similar or
      better than reported after repair with metallic plates or external fixation in
      Toy breed dogs. No radiographic signs of osteopenia were identified under the
      plate during follow-up. CLINICAL RELEVANCE: Biodegradable polylactide plates
      could be considered as an alternative to metal plates for radial fracture repair
      in Toy breed dogs, however available plates are likely not strong enough when
      used as a single plate. Implant removal is usually not needed.

PMID- 15720592
TI  - An in vitro biomechanical comparison of the breaking strength and stiffness of
      polydioxanone (sizes 2, 7) and polyglactin 910 (sizes 3, 6) in the equine linea
      alba.
AB  - OBJECTIVE: To determine failure strength, stiffness, and failure mode of 4 suture
      materials in equine linea alba. STUDY DESIGN: Randomized complete block design.
      SAMPLE POPULATION: Linea albas collected from 12 adult horses (mean weight, 475
      kg; mean age, 10 years). METHODS: The ventral abdominal fascia, including the
      linea alba, was collected and bisected along the linea alba into right and left
      halves. Each half was divided into four, 5-cm sections extending from the
      umbilicus cranially, and randomly assigned to 1 of 4 suture materials: 2
      polydioxanone (2 PD), 3 polyglactin 910 (3 PG), 6 polyglactin 910 (6 PG), and 7
      polydioxanone (7 PD). A single cycle to failure test was performed on each
      specimen at a distraction rate of 100 mm/min. Differences in failure strength and
      stiffness for the materials were evaluated using a mixed linear model with
      significance set at P<.05. RESULTS: In 94 of 96 test sections, constructs failed
      by suture failure. There were significant differences in failure strength
      (P<.0001) and stiffness (P<.001) among the suture/tissue constructs. 7 PD had the
      highest breaking strength (316.8 N) followed by 6 PG (281.3 N), 3 PG (229.9 N),
      and 2 PD (193.0 N). Six PG had the largest stiffness (14 N/mm) followed by 3 PG
      (12.7 N/mm), 7 PD (10.1 N/mm), and 2 PD (7.2 N/mm). Suture breaking strength and
      stiffness were not affected by linea or fascia thickness, individual horse, half
      of the linea alba, or abdominal wall position. Eighty-five (90.4%) suture loops
      failed adjacent the knot. CONCLUSIONS: When tested in single cycle to failure,
      suture material was more likely to fail than the linea alba. Larger suture
      materials had higher breaking strengths than smaller suture materials and
      stiffness was also affected by suture material and size. CLINICAL RELEVANCE:
      Given its high initial breaking strength and its relatively longer in vivo
      strength retention, 7 PD seems an appropriate choice of suture material for
      closure of the equine linea alba when maximal short-term failure strength is
      desired.

PMID- 15720593
TI  - Longitudinal bone transport for treatment of primary bone tumors in dogs:
      technique description and outcome in 9 dogs.
AB  - OBJECTIVE: To describe a surgical technique for bone transport osteogenesis (BTO)
      limb salvage and report outcome in 9 dogs with primary bone tumors. ANIMALS: Nine
      dogs with spontaneously occurring primary bone tumors. RESULTS: BTO surgery was
      performed as a primary means of limb salvage in 7 dogs and as a salvage procedure
      after catastrophic allograft infection and failure in 2 dogs. Mean defect size
      was 9.5 cm with a mean of 123 days distraction until docking. Mean time from
      surgery to fixator removal was 205 days. Minimum follow-up was 9 months. There
      were 2 histologically confirmed local recurrences where although limb function
      was excellent, eventually resulted in limb amputation. Limb function was good to
      excellent in all but 2 dogs; 1 was chronically non-weight bearing before BTO
      surgery because of complications associated with an allograft limb salvage that
      had been performed previously on the same limb. The cause of lameness in the
      other dog was undetermined. CONCLUSIONS: BTO limb salvage can be successful in
      dogs with primary bone tumors. Whereas allograft limb salvage may be simpler from
      an initial management perspective, BTO has some unique advantages when compared
      with the allograft technique. CLINICAL RELEVANCE: BTO has an emerging role in
      limb salvage surgery for dogs with primary bone tumors. BTO provides excellent
      long-term outcomes in some dogs with primary bone tumors and will likely become
      increasingly more attractive as technique modifications allow the duration of the
      treatment to be shortened.

PMID- 15720594
TI  - Evaluation of a percutaneously controlled hydraulic occluder in a rat model of
      gradual venous occlusion.
AB  - OBJECTIVE: To evaluate the efficacy of a percutaneously controlled hydraulic
      occluder (HO) in a rat model of gradual venous occlusion. STUDY DESIGN:
      Experimental study. ANIMALS: Ten male Sprague-Dawley rats. METHODS: HOs and
      perivascular transit time ultrasound flow probes were applied to the caudal vena
      cava (CVC). Occluders in group I rats (n=6) were gradually attenuated over 8
      weeks, whereas occluders in group II rats (n=4) were not attenuated. Vena caval
      blood flow measurements were performed weekly in all rats for 8 weeks. After
      euthanasia, the CVC was evaluated grossly and by histopathology. RESULTS:
      Premature occlusion of the vena cava occurred during the 1st week in 3 rats (1 in
      group I, 2 in group II) because of kinking of the vena cava between the HO and
      the flow probe. For the remaining rats, mean blood flow in group I decreased
      significantly from 40.71 mL/min/kg at baseline to 4.68 mL/min/kg at 8 weeks
      (P=.0094, power=0.91). Group II rats maintained vena caval blood flow at all
      times during the study. Complete occlusion of the vena cava was confirmed at
      necropsy in all group I rats. CONCLUSIONS: Gradual occlusion of the CVC of rats
      was achieved with HOs over 8 weeks. This model is limited by the size of the
      experimental animals and comparatively large implants. CLINICAL RELEVANCE: HOs
      may provide a method for gradual occlusion of congenital portosystemic shunts.

PMID- 15720595
TI  - Coxofemoral arthroscopy and total hip arthroplasty for management of intermediate
      grade fibrosarcoma in a dog.
AB  - OBJECTIVE: To report the use of arthroscopy and total hip arthroplasty (THA) for
      management of intermediate grade fibrosarcoma of the femoral head in a dog. STUDY
      DESIGN: Clinical case report. ANIMAL: A 6-year-old spayed female Rottweiler
      presented for evaluation of acute-onset of lameness of the right pelvic limb of
      approximately 10 days duration. METHODS: Coxofemoral arthroscopy was performed to
      obtain fine needle aspiration and Jamshidi biopsy of a lytic lesion of the
      femoral head. A cemented THA was performed removing as much of the femoral neck
      and proximal femur as possible while not compromising implant or joint stability.
      RESULTS: Histologic evaluation of specimens from the femoral head and neck
      remnants confirmed an intermediate grade fibrosarcoma. Fifteen months after THA,
      subjectively there was normal use of the right limb with only limited decrease in
      range of motion and mild muscular atrophy. Radiographs demonstrated stationary
      positioning of the THA implants. CONCLUSIONS: Arthroscopy of the coxofemoral
      joint is an effective diagnostic tool for evaluation of disease of the articular
      structures and canine total hip replacement may be an appropriate means of limb
      salvage in rare cases of disease of the femoral head. CLINICAL RELEVANCE: This
      case provides support for the use of coxofemoral arthroscopy as a diagnostic tool
      as well as an aid in acquiring representative intraarticular tissue samples.
      Additionally, the case presented demonstrates the potential use of THA as a limb
      sparing technique in cases of disease affecting the femoral head of dogs.

PMID- 15720596
TI  - Comparison of two laparoscopic suture patterns for repair of experimentally
      ruptured urinary bladders in normal neonatal calves.
AB  - OBJECTIVE: To compare 2 laparoscopic suture patterns for repair of experimentally
      ruptured urinary bladders in normal neonatal calves. STUDY DESIGN: Experimental
      surgical study. ANIMALS: Thirty male Holstein calves. METHODS: A bladder defect
      was created in 24 anesthetized calves (day 0). They were randomly divided into 4
      groups (n=6/group). In groups 1 and 3, the defect was closed laparoscopically
      using a one layer full thickness simple continuous (FTSC) suture pattern (pattern
      A). In groups 2 and 4, the defect was closed laparoscopically in 2 layers using a
      FTSC suture pattern followed by Lembert continuous suture pattern (pattern B).
      Groups 1 and 2 calves were euthanatized at the end of the surgery and groups 3
      and 4 at day 10. Six healthy calves were also euthanatized and used as a control
      group. The bladders were harvested and tested for bursting strength (BS). The
      surgical time (ST) data from the two groups for each pattern were pooled. A
      Student t-test was used to compare ST data. For the BS data, a 2-factor ANOVA
      test with post-hoc Student t-test was used to determine if treatment, time, or
      treatment-time interaction was significant. A Dunnett's test was used to compare
      BS of the 4 treatment groups to the control group. P<.05 was considered
      significant. RESULTS: Mean ST was significantly shorter for pattern A than for
      pattern B. In all treatment groups, the mean bladder BS (MBBS) was significantly
      lower than the MBBS for the control group. The MBBS was significantly lower for
      group 1 than for group 2. There was no significant difference in the MBBS between
      groups 3 and 4. CONCLUSION: In this study, a 1-layer laparoscopic closure
      technique had advantages compared with 2-layer laparoscopic closure technique.
      Further work is required before a 1-layer laparoscopic closure technique can be
      recommended clinically. CLINICAL RELEVANCE: One-layer bladder closure is fast and
      safe in clinically normal calves and permits additional research to evaluate its
      safety in foals and clinical ruptures.

PMID- 15720597
TI  - Arthroscopic treatment of temporomandibular joint sepsis in a horse.
AB  - OBJECTIVE: To report arthroscopic debridement and lavage of a septic
      temporomandibular joint (TMJ) in a horse. DESIGN: Clinical case report. ANIMALS:
      A 12-year-old Thoroughbred mare. METHODS: Arthroscopic investigation of the
      dorsal joint pouch of the right TMJ was made through a stab incision into the
      dorsocaudal compartment. Mechanized resection of synovium and fibrinous debris
      combined with copious lavage, and intra-articular and systemic antibiotic
      administration was used to treat the septic TMJ. RESULTS: Arthroscopic
      debridement and lavage of the TMJ, in combination with intra-articular and
      systemic antimicrobials resulted in resolution of sepsis. Eight months post
      operatively, there was no clinical evidence of degenerative joint disease or
      ankylosis of the TMJ. CONCLUSION: TMJ sepsis is rare in horses, however, standard
      arthroscopic equipment can be used in the management of this condition with
      minimal complications. CLINICAL RELEVANCE: Arthroscopic debridement and lavage
      should be considered for evaluation and initial treatment of TMJ sepsis in
      horses.

PMID- 15720598
TI  - Clinical evaluation of random skin flaps based on the subdermal plexus secured
      with sutures or sutures and cyanoacrylate adhesive for reconstructive surgery in
      dogs.
AB  - OBJECTIVE: To evaluate the use of subdermal plexus skin flaps for closing defects
      after excision of cutaneous and subcutaneous tumors in dogs and to compare
      outcome of flaps secured with sutures and those secured with butyl-cyanoacrylate
      and intermittent sutures. STUDY DESIGN: Clinical study. ANIMALS: Fifteen dogs.
      METHODS: After excision of cutaneous or subcutaneous tumors the skin defect was
      reconstructed by random flaps based on the subdermal plexus. Flap skin edges were
      apposed with simple interrupted 4-0 monofilament nylon sutures (group 1; 5 dogs)
      or nylon sutures alternated with butyl-cyanoacrylate adhesive (group 2; 10 dogs).
      Flaps were evaluated every 48 hours when bandages were changed, until complete
      healing. RESULTS: Random flaps based on the subdermal plexus were effectively
      used to close wound defects; mean flap survival was 89%. Partial flap necrosis
      occurred in 4 dogs. Wound margins apposed with butyl-cyanoacrylate had thinner
      and more esthetic scars than sutured margins. CONCLUSION: Random flaps based on
      the subdermal plexus proved to be versatile for covering limb wounds after
      excision of cutaneous or subcutaneous tumors. Mean survival rate was comparable
      to that reported for axial pattern flaps. Butyl-cyanoacrylate adhesive was easy
      to apply, allowed accurate margin apposition with good cosmetic outcome and
      reduced sutures needed. CLINICAL RELEVANCE: Cyanoacrylate adhesive should be
      considered in lieu of suture closure to secure random skin flaps based on the
      subdermal plexus in dogs.

PMID- 15720599
TI  - The effect of cisterna chyli ablation combined with thoracic duct ligation on
      abdominal lymphatic drainage.
AB  - OBJECTIVE: To evaluate the effect of cisterna chyli ablation (CCA) and thoracic
      duct ligation (TDL) on abdominal lymphatic drainage in normal dogs. STUDY DESIGN:
      Experimental study. ANIMALS: Nine female beagle dogs. METHODS: TDL was performed
      in 3 dogs and was combined with CCA (CCA-TDL) and local omentalization in 6 dogs.
      Contrast lymphangiography was attempted in all dogs immediately before and after
      TDL. Dogs were reanesthetized at 31-37 days for lymphatic studies by new
      methylene blue (NMB) injection into a mesenteric lymph node and by contrast
      lymphangiography. RESULTS: In 6 CCA-TDL dogs, 2 had direct shunting of contrast
      from the lymphatic system into major abdominal veins, 3 had contrast material
      that dissipated into abdominal vessels within the mesenteric root, and 1 had
      shunting into the azygous vein. NMB was not observed within the omental pedicle
      after CCA-TDL. Chylous drainage was by the azygous vein in all 3 TDL dogs.
      CONCLUSIONS: CCA-TDL disrupted chylous drainage to the thoracic duct and resulted
      in direct intraabdominal lymphaticovenous anastomoses identified by shunting of
      lymphatic flow directly into the abdominal vasculature in 5 of 6 CCA-TDL dogs.
      Omentalization of the cisternal ablation site was not beneficial in augmenting
      extrathoracic lymphatic drainage and is not recommended with CCA-TDL. CLINICAL
      RELEVANCE: CCA-TDL represents a novel approach to surgical redirection of chylous
      drainage to the venous circulation outside of the thorax and may be useful in the
      treatment of spontaneous chylothorax in the dog.

PMID- 15720600
TI  - Limb-sparing surgery in a dog with osteosarcoma of the proximal femur.
AB  - OBJECTIVE: To report successful limb-sparing surgery in a dog with a proximal
      femoral osteosarcoma (OSA) using a composite allograft-prosthetic technique.
      STUDY DESIGN: Case report. ANIMAL: Client-owned dog. METHODS: A stage IIB OSA of
      the proximal aspect of the femur was resected in accordance with oncologic and
      limb-sparing principles. The osseous defect was reconstructed with a proximal
      femoral allograft and cemented, long-stemmed femoral prosthesis. Soft tissue
      reconstruction was achieved by suturing host tendons to their respective
      allogeneic tendons on the allograft. Coxofemoral joint function was preserved
      using standard total hip arthroplasty techniques. RESULTS: Limb-sparing surgery
      of the proximal aspect of the femur using a composite allograft-prosthetic
      technique resulted in excellent limb function. Postoperative complications
      included aseptic loosening of the femoral composite graft and allograft nonunion,
      which required revision, traumatic implant luxation, and local tumor recurrence.
      Limb function was excellent after surgical stabilization of the allograft
      nonunion but deteriorated after implant luxation 270 days postlimb-sparing
      surgery. Pulmonary and skeletal metastases were diagnosed and local tumor
      recurrence suspected 596 and 650 days postoperatively, respectively. The dog was
      euthanatized 688 days after limb-sparing surgery as a result of progressive local
      and metastatic disease. CONCLUSIONS AND CLINICAL RELEVANCE: Limb-sparing surgery
      for dogs with primary bone tumors of the proximal aspect of the femur is feasible
      with good functional results.

PMID- 15720601
TI  - Reconstruction of the lower eyelid by third eyelid lateral advancement and local
      transposition cutaneous flap after "en bloc" resection of squamous cell carcinoma
      in 5 cats.
AB  - OBJECTIVE: To describe a novel technique for blepharoplasty to cover a tissue
      defect involving >/=50% of the lower eyelid. STUDY DESIGN: Prospective clinical
      study. ANIMALS: Five cats with lower eyelid squamous cell carcinoma (SCC).
      METHODS: En bloc resection of SCC by removing >/=50% of the lower lid with either
      the medial or lateral canthus was performed without other adjunctive treatment
      for SCC. The lid defect was reconstructed with a transposition skin flap derived
      from the frontal (medial defect) or temporal (lateral defect) region. The third
      eyelid was advanced laterally without dissection from its insertion; its outer
      conjunctival layer was removed, and the skin flap was sutured with single
      interrupted sutures dorsally over the nictitating membrane, ventrally to the
      cutaneous edge of the surgical wound and medially or laterally (depending on the
      canthus removed) to the skin of the remaining lower lid. RESULTS: Satisfactory
      cosmetic and functional results were achieved and the Schirmer tear tests were
      normal. In 2 cats, the skin flap needed monthly hair trimming to avoid corneal
      lesions. CONCLUSIONS: After en bloc resection of SCC involving >/=50% of the
      lower eyelid, reconstruction can be achieved by relocation of the third eyelid
      and use of a cutaneous transposition flap sutured to the scarified external
      surface of the third eyelid. Eyelid apposition and lacrimal function were
      preserved. CLINICAL RELEVANCE: Blepharoplasty using a cutaneous transposition
      flap sutured to the scarified surface of a relocated third eyelid should be
      considered for reconstruction of lower eyelid defects with >/=50% tissue loss of
      the lid margin.

PMID- 15720602
TI  - Methods of gradual vascular occlusion and their applications in treatment of
      congenital portosystemic shunts in dogs: a review.
AB  - OBJECTIVE: To provide a comprehensive review of the experimental and clinical
      data related to gradual vascular occlusion of congenital portosystemic shunts
      (CPS) in dogs. STUDY DESIGN: Literature review. METHODS: PubMed literature search
      (1966-2004). RESULTS: Surgical intervention and complete vascular occlusion have
      been recommended for CPS therapy in dogs; however, acute complete ligation of CPS
      is often associated with life-threatening portal hypertension. Recently, several
      investigators have attempted to reduce the risk of postoperative portal
      hypertension by using gradual vascular occlusion. Successful vascular occlusion
      has been achieved using partial ligation with silk suture, ameroid constrictors,
      cellophane bands, thrombogenic coils and hydraulic vascular occluders. Objective
      comparisons of the reliability and rate of vascular occlusion produced by each of
      these methods have been limited by differences in experimental models and a lack
      of definitive follow up evaluation in some clinical studies. CONCLUSIONS: Gradual
      vascular occlusion is widely used in the clinical treatment of CPS in dogs.
      Objective evaluation of the experimental and clinical data on each of the
      techniques for gradual vascular occlusion is necessary for informed clinical
      practice and for the planning of future research into this important area.
      CLINICAL RELEVANCE: Even from the limited data available, it is clear that the
      ideal method for gradual vascular occlusion of CPS has yet to be identified.

PMID- 15720604
TI  - HBV NAT positive [corrected] blood donors in the early and late stages of HBV
      infection: analyses of the window period and kinetics of HBV DNA.
AB  - BACKGROUND AND OBJECTIVES: The Japanese Red Cross (JRC) carries out nucleic acid
      amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV)
      and human immunodeficiency virus-1 (HIV-1) by using a multiplex (MPX) reagent.
      Screening is undertaken on serologically negative units. In this study we
      characterized HBV NAT-positive donations individually and analysed the window
      period and kinetics of HBV DNA, during acute infection, in follow-up studies.
      MATERIALS AND METHODS: Two hundred and seventy-seven HBV DNA-positive donations
      have been identified in Japan since the introduction of NAT screening of 50
      donation minipools. The viral loads and genotypes of these HBV DNA-positive
      donations were characterized. The doubling time and half-life of HBV was
      estimated from the data of 123 follow-up donors. The sensitivity of the NAT
      system (based on 50-donation minipools) was compared with the sensitivities of
      the enzyme immunoassay (EIA) and the chemiluminescence immunoassay (CLIA).
      Samples that were CLIA negative, but with > 10(4) copies/ml of HBV DNA, were
      analysed by sequencing the hepatitis B surface antigen (HBsAg) region. RESULTS:
      Out of 277 HBV NAT-positive samples, 125 (45%) were found to have an increasing
      viral load and 45 (16%) a decreasing viral load. Forty per cent of HBV NAT
      positive samples with an increasing viral load, and 33% of those with a
      decreasing viral load, were negative when tested by using the CLIA. No mutations
      related to escape mutants were found in the samples that were CLIA negative but
      with HBV DNA loads of > 10(4) copies/ml. The median HBV doubling time was 2.6
      days (n = 93, 1.3-15.2 days) and the half-life was 1.6 days (n = 55, 0.9-6.3
      days). Some kinetic difference was observed between genotypes A and B.
      CONCLUSIONS: HBV NAT screening detected HBV DNA in both early (the so-called
      serological window period) and late stages of acute HBV infection.

PMID- 15720605
TI  - Hepatitis B virus genotypes and precore mutations in Scottish blood donors.
AB  - BACKGROUND AND OBJECTIVES: This study was carried out to determine the frequency
      of hepatitis B virus (HBV) core promoter variants (nucleotide positions 1762,
      1764) and precore variants (nucleotide position 1896) in hepatitis B surface
      antigen (HBsAg)-positive Scottish blood donors. HBV genotypes present in this
      population were also identified. MATERIALS AND METHODS: A total of 85 HBsAg
      positive blood donor samples were included in the study. Of these, 79 were
      polymerase chain reaction (PCR) positive and had sequence and mutation
      information. They were divided into two groups: group 1 (23 individuals) were
      hepatitis B e antigen (HBeAg)-positive and negative for antibody to HBe (anti
      HBe); and group 2 (56 individuals) were HBeAg negative and positive for anti-HBe.
      A line probe assay was used to detect mutations, and a comparison was made by
      using direct sequence analysis. A different line probe assay was used to identify
      HBV genotype. RESULTS: The frequencies of mutations in group 1 were 22% each for
      mutations 1762, 1764 and 1896, increasing to 26%, 35% and 55% in group 2,
      respectively. By contrast, direct sequence analysis failed to identify 70% of
      wild-type/mutant mixes. The prevalence of viral genotypes was 41% for genotype A,
      12% for genotype B, 5% for genotype C, 30% for genotype D and 12% for mixed
      genotype infections. Precore mutations were seen in 10%, 88%, 25% and 74% of
      genotypes A, B, C and D, respectively. CONCLUSIONS: The results indicate that
      core promoter and/or precore mutants may be under-reported. The combination of
      HBV PCR and line probe assays is useful for supplementing HBV serological tests.
      Non-Caucasian genotypes are present in the UK blood-donating population and will
      therefore affect the demographics of HBV infection.

PMID- 15720606
TI  - Six years' experience of using the BacT/ALERT system to screen all platelet
      concentrates, and additional testing of outdated platelet concentrates to
      estimate the frequency of false-negative results.
AB  - BACKGROUND AND OBJECTIVES: Approximately 1 in every 2000 units of platelets is
      contaminated with bacteria. The BacT/ALERT automated blood culture system can be
      used to screen platelet concentrates (PCs) for bacterial contamination. MATERIALS
      AND METHODS: Data were collected from May 1998 until May 2004. The number of PCs
      tested during this period was 36 896, most of which were produced from pools of
      four buffy-coats. On the day following blood collection or platelet apheresis, a
      5-10 ml sample of the PC was aseptically transferred to a BacT/ALERT culture
      bottle for detection of aerobic bacteria. The sample was monitored for bacterial
      growth during the entire storage period of the PC (6.5 days). When a positive
      signal was generated, the culture bottle, the PC and the erythrocyte concentrates
      were tested for bacterial growth. In order to determine the frequency of false
      negative BacT/ALERT signals, 1061 outdated PCs were tested during the period from
      May 2002 to May 2004. RESULTS: Eighty-eight positive signals were detected by the
      BacT/ALERT system, of which 12 were interpreted as truly positive. Fourteen
      signals were interpreted as truly false positive. Thirty-three signals were
      interpreted to be probably false positive. Two of 1061 outdated units tested
      positive, and Bacillus spp. and Staphylococcus epidermidis, respectively, were
      isolated from these PCs. CONCLUSIONS: Between 0.03% and 0.12% of the PCs were
      contaminated with bacteria. BacT/ALERT is an efficient tool for monitoring PCs
      for bacterial contamination; however, it is important to realize that false
      negative results may occur.

PMID- 15720607
TI  - The efficacy of a malarial antibody enzyme immunoassay for establishing the
      reinstatement status of blood donors potentially exposed to malaria.
AB  - BACKGROUND AND OBJECTIVES: The two key objectives of the study were, first, to
      evaluate the sensitivity and specificity of a recombinant antigen-based malarial
      enzyme-linked immunoassay (EIA) and, second, to estimate the risk associated with
      implementing this test with a shortened cellular component restriction period (6
      months rather than the standard 12-36 months) for blood donors with a malarial
      risk exposure. MATERIALS AND METHODS: Blood donors were recruited into four
      distinct groups [non-exposed (control), malarial area 'visitors', 'residents' and
      'previous infection') and screened by using the Newmarket malarial antibody EIA.
      Assay specificity was evaluated in unexposed blood donors, and sensitivity was
      determined in acute clinical samples. RESULTS: No parasitaemic donors were
      detected amongst 337 malarial 'visitors' who had returned from a malaria-endemic
      area less than 6 months previously, or for 402 'visitors' or 'residents' who had
      returned from a malaria-endemic area more than 6 months previously. The incidence
      of malarial antibodies within the exposed blood donor groups was 1.33% (10/751).
      In acute clinical non-donor samples, the Newmarket EIA detected 106/108 (98.1;
      93.5-99.5%) 'film' positive Plasmodium falciparum infections and 12/12 (100, 75.7
      100.0%) P. vivax infections. The estimated additional risk exposure of the
      proposed new strategy was one infectious P. falciparum donation per 175 years or
      1 per 4.2 years for P. vivax. CONCLUSIONS: The study findings support the
      efficacy and safety of a targeted screening strategy combining antibody screening
      with a 6-month cellular component restriction period for donors with a declared
      malarial risk.

PMID- 15720608
TI  - Strict red blood cell transfusion guideline reduces the need for transfusions in
      very-low-birthweight infants in the first 4 weeks of life: a multicentre trial.
AB  - BACKGROUND AND OBJECTIVES: Very-low-birthweight infants are among the most
      heavily transfused patients. The objective of this study was to verify if the
      introduction of a strict guideline would reduce the need for red blood cell
      transfusions in the first 4 weeks of life in these neonates. MATERIALS AND
      METHODS: This was a multicentre prospective study of two cohorts of very-low
      birthweight infants transfused in accordance with the recommendations of a
      neonatologist (Phase 1) or according to previously published guidelines (Phase
      2). RESULTS: In the first 28 days of life, 102 patients (68.5%) in Phase 1 and
      117 (59.7%) in Phase 2 were transfused. The number of transfusions was 1.9 +/-
      2.0 in Phase 1 and 1.4 +/- 1.6 in Phase 2 (P = 0.01). After adjusting for
      gestational age, blood loss and the presence of respiratory distress syndrome,
      the strict guideline reduced the number of transfusions in 17.6% (IC 95%-30.5% to
      -2.6%). CONCLUSIONS: The strict guideline was effective in reducing erythrocyte
      transfusions in very-low-birthweight infants.

PMID- 15720609
TI  - First year donation patterns predict long-term commitment for first-time donors.
AB  - BACKGROUND AND OBJECTIVES: Converting first-time donors to become regular donors
      continues to be a challenge facing blood centres. We examined whether first-time
      donors with frequent return in the first 12 months were more likely to become
      regular donors. SUBJECTS AND METHODS: The donation histories of 179 409 community
      whole-blood donors, whose first-time donation in 1991 was negative on donor
      screening tests, were evaluated. Donors were categorized by the number of
      donations made in the 12 months after (and including) their first donation. The
      donor return pattern in the subsequent 6 years, and its association with first
      year donation frequency and demographics, was evaluated by using logistic
      regression analysis. A 'regular donor' was defined as one who returned to donate
      in at least 4 of the 6 years of follow-up. RESULTS: First-year donation frequency
      was significantly correlated with long-term donor return (P < 0.0001). Among
      those giving 1, 2, 3, 4 and > or = 5 donations in the first year, 4%, 11%, 21%,
      32% and 42%, respectively, became regular donors (P < 0.0001). Similar
      associations between donation pattern and donor return behaviour were observed
      after adjusting for demographic variables (P < 0.0001). CONCLUSIONS: Strategies
      aimed at encouraging current donors to donate more frequently during the first
      year may help to establish a regular donation behaviour.

PMID- 15720610
TI  - Survival of baboon biotin-X-N-hydroxysuccinimide and (111)In-oxine-labelled
      autologous fresh and lyophilized reconstituted platelets.
AB  - BACKGROUND AND OBJECTIVES: In accordance with Food and Drug Administration (FDA)
      regulations, platelets can be stored in the liquid state at 22 degrees C for only
      5 days. Platelets frozen with 6% dimethylsulphoxide (DMSO) can be stored at -80
      degrees C for 2 years, and platelets frozen with 5% DMSO can be stored at -150
      degrees C for 3 years. Studies are being conducted to determine the effects of
      lyophilization of platelets. In the present study, we assessed the survival of
      autologous lyophilized-reconstituted platelets in the baboon. MATERIALS AND
      METHODS: We studied fresh baboon platelets and baboon platelets that had been
      treated with paraformaldehyde, frozen, lyophilized, thawed and reconstituted.
      Aliquots of these platelets were labelled with (111)In-oxine or biotin-X-N
      hydroxysuccinimide (biotin-X-NHS) before autotransfusion, and measurements were
      made of the in vivo recovery and lifespan. We also evaluated the response of
      fresh and lyophilized platelets to in vitro agonists by measuring the level of
      platelet surface markers and heterotypic aggregates in the peripheral blood
      following the autotransfusions. RESULTS: The (111)In-oxine- or biotin-X-NHS
      labelled lyophilized, reconstituted platelets exhibited survival times of less
      than 15 min. These platelets did not respond to stimulation with agonists to
      decrease platelet GPIb and increase platelet P-selectin and platelet GPIIb-IIIa
      levels 1 min post-transfusion and they accumulated more procoagulant factor V
      than did the fresh platelets. CONCLUSIONS: Lyophilized reconstituted baboon
      platelets labelled with (111)In-oxine or biotin-X-NHS before autotransfusion
      exhibited an in vivo circulation time of less than 15 min. Further study of the
      lyophilized, reconstituted platelets is required to evaluate their haemostatic
      function.

PMID- 15720611
TI  - Anti-D alloimmunization by weak D type 1 red blood cells with a very low antigen
      density.

PMID- 15720612
TI  - Report of the First International Workshop on molecular blood group genotyping.
AB  - The use of molecular genetic technology for blood group typing is becoming
      routine procedure in many reference laboratories worldwide. A First International
      Workshop was organized on behalf of the International Society of Blood
      Transfusion (ISBT) and the International Council for Standardization in
      Haematology (ICSH). Thirty laboratories that provide a molecular diagnostic
      service participated in the workshop. Six samples were distributed: two
      represented DNA from transfusion-dependent patients for testing for multiple
      polymorphisms; two represented fetal DNA prepared from amniotic fluid for RhD,
      Rhc and K-testing; and two represented plasma from RhD-negative pregnant women
      for fetal RhD testing. Error rates varied from 0 to 11% for different
      polymorphisms. A consensus arising from discussion on the workshop results
      between participants at a feedback meeting and by e-mail has resulted in seven
      recommendations for molecular blood group genotyping. Further international
      workshops will take place every 2 years, with a more limited exercise being
      organized in the intervening years.

PMID- 15720613
TI  - An international collaborative study to replace the 1st international standard
      for prekallikrein activator.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to replace the 1st
      International Standard (IS) for prekallikrein activator (PKA) (code 82/530) with
      a new IS and European Biological Reference Preparation (BRP). The new standards
      were freeze dried 20% albumin solution containing PKA, the same solution that is
      tested using these standards. Aspects of the methodology for PKA determination
      were also examined as part of this study. MATERIALS AND METHODS: A batch of 20%
      albumin containing approximately 30 IU/ml was donated by a manufacturer of blood
      products and dispensed into ampoules at the National Institute for Biological
      Standards and Control (NIBSC) to create the candidate IS (02/168, sample B in the
      study) and at the European Directorate for the Quality of Medicines (EDQM) to
      create the candidate BRP (sample C in the study). The concentration of PKA in
      these preparations was determined in an international collaborative study
      involving 31 laboratories from 17 countries worldwide in comparison with the 1st
      IS for PKA (82/530) containing 85 IU of PKA per ampoule. Participants were
      requested to perform their own in-house method, based on the current Ph. Eur.
      monograph for determination of PKA in albumin solutions. Participants were
      provided with sufficient samples to perform two or three assays and were asked to
      use their local prekallikrein substrate (PKS) and also to use a commercial PKS
      provided as part of the study, in order to investigate the importance of the
      source of PKS on the final potency values. RESULTS: Samples B and C emerged with
      identical PKA concentrations of 29 IU/ml, very close to the expected value. This
      figure was determined using a variety of statistical methods, with the
      participants' own calculated values and values calculated centrally at the EDQM
      using raw data. The value of 29 IU/ml was consistent and independent of the
      method of calculation, although interlaboratory variability was more sensitive to
      the statistical analysis method. There was no statistically significant
      difference in mean potencies when comparing results with the laboratories' own
      local substrate and the substrate provided for the study. All stability studies
      indicate that these lyophilized preparations of PKA in 20% albumin are extremely
      stable. CONCLUSIONS: Samples B and C were established as the 2nd IS (code 02/168)
      and PKA activator in albumin BRP batch 1 (Y0000263), respectively, with a potency
      of 29 IU per ampoule. Results from this study indicate that testing for PKA in
      albumin may be less sensitive to the source of PKS than previously feared. The
      study highlights a number of methodological issues that may need revising in the
      Ph. Eur. general chapter 2.6.15.

PMID- 15720615
TI  - Plant evolutionary ecology.

PMID- 15720616
TI  - NO way to die--nitric oxide, programmed cell death and xylogenesis.

PMID- 15720617
TI  - Proanthocyanidins--a final frontier in flavonoid research?
AB  - Proanthocyanidins are oligomeric and polymeric end products of the flavonoid
      biosynthetic pathway. They are present in the fruits, bark, leaves and seeds of
      many plants, where they provide protection against predation. At the same time
      they give flavor and astringency to beverages such as wine, fruit juices and
      teas, and are increasingly recognized as having beneficial effects on human
      health. The presence of proanthocyanidins is also a major quality factor for
      forage crops. The past 2 years have seen important breakthroughs in our
      understanding of the biosynthesis of the building blocks of proanthocyanidins,
      the flavan-3-ols (+)-catechin and (-)-epicatechin. However, virtually nothing is
      known about the ways in which these units are assembled into the corresponding
      oligomers in vivo. Molecular genetic approaches are leading to an understanding
      of the regulatory genes that control proanthocyanidin biosynthesis, and this
      information, together with increased knowledge of the enzymes specific for the
      pathway, will facilitate the genetic engineering of plants for introduction of
      value-added nutraceutical and forage quality traits.

PMID- 15720618
TI  - Cell biology of the plant Golgi apparatus.
AB  - The higher plant Golgi apparatus, comprising many individual stacks of membrane
      bounded cisternae, is one of the most enigmatic of the cytoplasmic organelles.
      Not only can the stacks receive material from the endoplasmic reticulum, process
      it and target it to the correct cellular destination, but they can also
      synthesise and export complex carbohydrates and lipids and most likely act as one
      end point of the endocytic pathway. In many cells such processing and sorting can
      take place while the stacks are moving within the cytoplasm and, remarkably, the
      organelle manages to retain its structural integrity. This review considers some
      of the latest data and views on transport both to and from the Golgi and the
      mechanisms by which such activity is regulated.

PMID- 15720619
TI  - The evolution of polymorphic sexual systems in daffodils (Narcissus).
AB  - Narcissus, the daffodil genus, exhibits an unusual diversity of sexual systems,
      with populations that are monomorphic, dimorphic or trimorphic for style length.
      Associated with this variation are striking differences among species in floral
      morphology and pollination biology. This diversity provides an opportunity to
      investigate the evolution of mating polymorphisms, and to determine how floral
      morphology promotes transitions among sexual systems. Because of the absence of
      heteromorphic incompatibility in Narcissus, floral morphology plays a key role in
      governing patterns of outcrossed mating. Phylogenetic evidence indicates that
      stylar monomorphism is ancestral in the genus, with multiple origins of stylar
      polymorphism, including independent origins of stigma-height dimorphism, distyly
      and tristyly. Sexual polymorphisms have evolved only in lineages with narrow
      floral tubes that are pollinated by Lepidoptera and/or long-tongued bees.
      Populations of polymorphic Narcissus species are typically dominated by the long
      styled morph and display imperfect reciprocity in the positions of sexual organs.
      These features are consequences of the unusual association between stylar
      polymorphism and a self-incompatibility system that permits intramorph mating.

PMID- 15720620
TI  - Family level inbreeding depression and the evolution of plant mating systems.
AB  - Variation in the magnitude of inbreeding depression (ID) among families may have
      important consequences for mating system evolution. Experimental studies have
      shown that such variation is a common feature of natural plant populations.
      Unfortunately, the genetic and evolutionary significance of family level
      estimates remains obscure. Almost any kind of genetic variation will generate
      differences in ID among families, and as a consequence, a non-zero variance in
      family level ID is not sufficient to distinguish genetic architectures with
      wholly different implications for mating system evolution. Quantitative genetic
      methods provide a means to extract more information from ID experiments.
      Estimates of quantitative genetic variance components directly inform questions
      about the genetic basis of ID and should ultimately allow tests of alternative
      theories of mating system evolution.

PMID- 15720621
TI  - Evolution under tight linkage to mating type.
AB  - Recent large-scale sequencing studies of mating type loci in a number of
      organisms offer insight into the origin and evolution of these genomic regions.
      Extensive tracts containing genes with a wide diversity of functions typically
      cosegregate with mating type. Cases in which mating type determination entails
      complementarity between distinct transcription units may descend from systems in
      which close physical linkage facilitated the coordinated expression and
      cosegregation of the interacting genes. In response to the particular selection
      pressures associated with the maintenance of more than one mating type, this
      nucleus of low recombination may expand over evolutionary time, engulfing
      neighboring tracts bearing genes with no direct role in reproduction. This
      scenario is consistent with the present-day structure of some mating type loci,
      including regulators of homomorphic self-incompatibility in angiosperms (S-loci).
      Recombination suppression and enforced S-locus heterozygosity accelerate the
      accumulation of genetic load and promote genetic associations between S-alleles
      and degenerating genes in cosegregating tracts. This S-allele-specific load may
      influence the evolution of self-incompatibility systems.

PMID- 15720622
TI  - Plant venereal diseases: insights from a messy metaphor.
AB  - The concept of plant venereal disease is examined from definitional, operational
      and axiomatic viewpoints. The transmission of many plant pathogens occurs during
      the flowering phase and is effected either by pollinators or by wind dispersal of
      spores from inflorescences. Attraction of insects by pseudo-flowers or sugary
      secretions also serves to spread many diseases. Given the diversity of processes
      involved, a simple all-encompassing parallel with animal venereal diseases is not
      possible. Operationally establishing the routes of disease transmission, as well
      as quantifying the relative magnitudes of these different routes, remains
      critical for understanding disease dynamics and controlling spread in
      agricultural contexts. From an axiomatic viewpoint, sexually transmitted diseases
      are characterized by frequency-dependent transmission, transmission in the adult
      stage, and by virulence effects involving sterility rather than mortality. These
      characteristics serve to differentiate the dynamics and evolution of sexually
      transmitted diseases from that of other diseases and are features that are also
      shared by many pollinator-transmitted diseases. However, the majority of plant
      diseases that involve the reproductive structures show a rich biology that defies
      easy categorization. The experimental convenience of plants and their pathogens
      is likely to play an important role in understanding the evolution of disease
      traits, irrespective of what descriptive terms are applied to the natural history
      of the transmission process.

PMID- 15720623
TI  - Toward a more trait-centered approach to diffuse (co)evolution.
AB  - How species evolve depends on the communities in which they are embedded. Here,
      we briefly review the ideas underlying concepts of diffuse coevolution,
      evolution, and selection. We discuss criteria to identify when evolution will be
      diffuse. We advocate a more explicitly trait-oriented approach to diffuse
      (co)evolution, and discuss how considering effects of interacting species on
      fitness alone tells us little about evolution. We endorse the view that diffuse
      evolution occurs whenever the response to selection by one interacting species on
      a given trait is altered by the presence of a second interacting species.
      Building on the work of others, we clarify and expand the criteria for diffuse
      evolution and present a simple experimental design that will allow the detection
      of diffuse selection. We argue that a greater focus on selection on specific
      traits and the evolutionary response to that selection will improve our
      conceptual understanding of how communities affect the evolution of species
      embedded within them.

PMID- 15720624
TI  - Direct evidence showing the effect of root surface iron plaque on arsenite and
      arsenate uptake into rice (Oryza sativa) roots.
AB  - The present study aimed to investigate the effects of root surface iron plaque on
      the uptake kinetics of arsenite and arsenate by excised roots of rice (Oryza
      sativa) seedlings. The results demonstrated that the presence of iron plaque
      enhanced arsenite and decreased arsenate uptake. Arsenite and arsenate uptake
      kinetics were adequately fitted by the Michaelis-Menten function in the absence
      of plaque, but produced poor fits to this function in the presence of plaque.
      Phosphate in the uptake solution did not have a significant effect on arsenite
      uptake irrespective of the presence of iron plaque; however phosphate had a
      significant effect on arsenate uptake. Without iron plaque, phosphate inhibited
      arsenate uptake. The presence of iron plaque diminished the effect of phosphate
      on arsenate uptake, possibly through a combined effect of arsenate desorption
      from iron plaque.

PMID- 15720625
TI  - Early events responsible for aluminum toxicity symptoms in suspension-cultured
      tobacco cells.
AB  - We investigated the aluminum (Al)-induced alterations in zeta potential, plasma
      membrane (PM) potential and intracellular calcium levels to elucidate their
      interaction with callose production induced by Al toxicity. A noninvasive
      confocal laser microscopy has been used to analyse the live tobacco (Nicotiana
      tabacum) cell events by means of fluorescent probes Fluo-3 acetoxymethyl ester
      (intracellular calcium) and DiBAC4 (PM potential) as well as to monitor callose
      accumulation. Log-phase cells showed no detectable changes in the PM potential
      during the first 30 min of Al treatment, but sustained large depolarization from
      60 min onwards. Measurement of zeta potential confirmed the depolarization effect
      of Al, but the kinetics were different. The Al-treated cells showed a moderate
      increase in intracellular Ca2+ levels and callose production in 1 h, which
      coincided with the time course of PM depolarization. Compared with the Al
      treatment, cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca(2+)
      ATPase, facilitated a higher increase in intracellular Ca2+ levels, but resulted
      in accumulation of only moderate levels of callose. Calcium channel modulators
      and Al induced similar levels of callose in the initial 1 h of treatment. Callose
      production induced by Al toxicity is dependent on both depolarization of the PM
      and an increase in intracellular Ca2+ levels.

PMID- 15720626
TI  - Zinc tolerance and hyperaccumulation in F1 and F2 offspring from intra and
      interecotype crosses of Thlaspi caerulescens.
AB  - The relationship between zinc (Zn) tolerance and hyperaccumulation in Thlaspi
      caerulescens was investigated from F1 and F2 crosses within and among
      metallicolous and nonmetallicolous Mediterranean populations. F1 offspring were
      grown on increasingly Zn-enriched soils to test Zn enrichment effects, and many
      families of F2 offspring were grown on a Zn-rich soil. Tolerance of F1 offspring
      depended on stress intensity. Tolerance of interecotype crosses was intermediate
      between that of the intraecotype crosses. No difference in Zn accumulation
      appeared among the F1 offspring from the three crosses involving metallicolous
      parents. Otherwise, none of these offspring exceeded the Zn hyperaccumulation
      threshold (10,000 mg kg(-1)), unlike the nonmetallicolous ones. The latter also
      showed the highest mortality. In some F2 families from interecotype crosses,
      hyperaccumulation values exceeded 15,000 mg kg(-1) in nontolerant offspring,
      whereas tolerant offspring displayed lower values (c. 10,000 mg kg(-1)). There
      was no difference between tolerant and nontolerant offspring when they showed low
      hyperaccumulation. Therefore, the relationship between tolerance and
      hyperaccumulation in F1 and F2 crosses depended on the hyperaccumulation level of
      plants.

PMID- 15720627
TI  - Nitric oxide production by the differentiating xylem of Zinnia elegans.
AB  - Nitric oxide (NO) is currently regarded as a signal molecule involved in plant
      cell differentiation and programmed cell death. Here, we investigated NO
      production in the differentiating xylem of Zinnia elegans by confocal laser
      scanning microscopy to answer the question of whether NO is produced during xylem
      differentiation. Results showed that NO production was mainly located in both
      phloem and xylem regardless of the cell differentiation status. However, there
      was evidence for a spatial NO gradient inversely related to the degree of xylem
      differentiation and a protoplastic NO burst was associated with the single cell
      layer of pro-differentiating thin-walled xylem cells. Confirmation of these
      results was obtained using trans-differentiating Z. elegans mesophyll cells. In
      this system, the scavenging of NO by means of 2-phenyl-4,4,5,5-tetramethyl
      imidazoline-1-oxyl-3-oxide (PTIO) inhibits tracheary element differentiation but
      increases cell viability. These results suggest that plant cells, which are just
      predetermined to irreversibly trans-differentiate in xylem elements, show a burst
      in NO production, this burst being sustained as long as secondary cell wall
      synthesis and cell autolysis are in progress.

PMID- 15720628
TI  - Components of apoplastic ascorbate use in Betula pendula leaves exposed to CO2
      and O3 enrichment.
AB  - Here, the aim was to estimate loads imposed on the apoplastic ascorbate (ASC)
      pool by enzymatic and nonenzymatic reactions in Betula pendula exposed to doubled
      CO2 and O3 concentrations in open-top chambers. Leaf apoplastic extracts were
      analysed for peroxidase and oxidase activities in vitro, using different
      substrates. Partial loads in vivo were deduced using measured kinetic constants
      and substituted-enzyme catalysis approaches. Ascorbate use in O3 scavenging was
      calculated using measured stomatal conductances and ASC concentrations. Under
      elevated O3, stomatal conductance and O3 uptake were higher. O3 fluxes to the
      plasmalemma were levelled off by higher apoplastic ASC concentrations. The effect
      of CO2 enrichment on ASC concentrations under elevated O3 was minor. Under
      ambient O3, the ascending hierarchy of ASC users was: peroxidases, O3 scavenging,
      oxidases, coniferyl alcohol re-reduction. Under elevated O3, ASC use in O3
      scavenging was higher than by oxidases. The redox state of ASC was not depressed
      by O3; there was no leaf injury. The cell wall/plasmalemma/cytosol system in
      birch had sufficient capacity to maintain ASC redox status in the apoplast,
      without necessity to restrict O3 uptake by stomatal closure.

PMID- 15720629
TI  - Dynamic light use and protection from excess light in upper canopy and coppice
      leaves of Nothofagus cunninghamii in an old growth, cool temperate rainforest in
      Victoria, Australia.
AB  - Responses to simulated sunflecks were examined in upper canopy and coppice leaves
      of Nothofagus cunninghamii growing in an old-growth rainforest gully in Victoria,
      Australia. Shaded leaves were exposed to a sudden increase in irradiance from 20
      to 1500 micromol m(-2) s(-1). Gas exchange and chlorophyll fluorescence were
      measured during a 10 min simulated sunfleck and, in the ensuing dark treatment,
      we examined the recovery of PS II efficiency and the conversion state of
      xanthophyll cycle pigments. Photosynthetic induction was rapid compared with
      tropical and northern hemisphere species. Stomatal conductance was relatively
      high in the shade and stomata did not directly control photosynthetic induction
      under these conditions. During simulated sunflecks, zeaxanthin was formed rapidly
      and photochemical efficiency was reduced. These processes were reversed within 30
      min in coppice leaves, but this took longer in upper canopy leaves. Poor drought
      tolerance and achieving a positive carbon balance in a shaded canopy may be
      functionally related to high stomatal conductance in the shade in N.
      cunninghamii. The more persistent reduction in photochemical efficiency of upper
      canopy leaves, which means less efficient light use in subsequent shade periods,
      but stronger protection from high light, may be related to the generally higher
      irradiance and longer duration of sunflecks in the upper canopy, but potentially
      reduces carbon gain during shade periods by 30%.

PMID- 15720630
TI  - The influence of root assimilated inorganic carbon on nitrogen
      acquisition/assimilation and carbon partitioning.
AB  - Understanding of the influences of root-zone CO2 concentration on nitrogen (N)
      metabolism is limited. The influences of root-zone CO2 concentration on growth, N
      uptake, N metabolism and the partitioning of root assimilated 14C were determined
      in tomato (Lycopersicon esculentum). Root, but not leaf, nitrate reductase
      activity was increased in plants supplied with increased root-zone CO2. Root
      phosphoenolpyruvate carboxylase activity was lower with NO3(-)- than with NH4(+)
      nutrition, and in the latter, was also suppressed by increased root-zone CO2.
      Increased growth rate in NO3(-)-fed plants with elevated root-zone CO2
      concentrations was associated with transfer of root-derived organic acids to the
      shoot and conversion to carbohydrates. With NH4(+)-fed plants, growth and total N
      were not altered by elevated root-zone CO2 concentrations, although 14C
      partitioning to amino acid synthesis was increased. Effects of root-zone CO2
      concentration on N uptake and metabolism over longer periods (> 1 d) were
      probably limited by feedback inhibition. Root-derived organic acids contributed
      to the carbon budget of the leaves through decarboxylation of the organic acids
      and photosynthetic refixation of released CO2.

PMID- 15720631
TI  - Fine root distribution and persistence under field conditions of three co
      occurring Great Basin species of different life form.
AB  - Fine roots of an annual grass, a perennial grass and a perennial shrub were
      examined. Based on life histories and tissue composition, we expected the
      greatest root persistence for the shrub and shortest for the annual grass. Roots
      were observed with minirhizotrons over 2 yr for number, length and diameter
      changes. A Cox proportional hazard regression correlated root persistence with
      soil water, depth, diameter and date of production. In 2001, grass roots had
      similar persistence times, but shrub roots had the shortest. In 2002, the annual
      had the longest median root persistence, the perennial grass intermediate and the
      perennial shrub had the shortest. All species responded similarly to the
      magnitude of seasonal precipitation; root numbers increased with favorable soil
      moisture and disappeared with drying; fewer, thinner roots at greater soil depths
      were found in the drier year (2001). Root persistence increased with soil
      moisture, diameter and earlier appearance in the spring. Plasticity in root
      morphology and placement was influenced by water availability, yet persistence
      was surprisingly contrary to expectations.

PMID- 15720632
TI  - Endolithic growth of two Lecidea lichens in granite from continental Antarctica
      detected by molecular and microscopy techniques.
AB  - Through the combined use of molecular and microscopy techniques, the endolithic
      lichens Lecidea cancriformis and Lecidea sp. were identified, even in the absence
      of fruiting bodies, and positioned under epilithic lichens. Cells of both algal
      and fungal symbionts were observed in fissures and cracks of the lithic substrate
      with no clear heteromerous structure. At the ultrastructural level, the two
      lichens differed in terms of their algal-fungal relationships. Only one genotype
      of Trebouxia ITS sequence was identified from specimens of Lecidea sp.,
      Umbilicaria aprina and Buellia frigida from the same zone, which could be mainly
      determined by low availability of alga in these extreme environments. These
      lichens showed features typical of both chasmoendolithic and euendolithic
      microorganisms. Signs of biogeophysical and biogeochemical action on the
      substrate were detected close to fungal cells. This action seemed to be mainly
      conditioned by the local physico-chemical features of the substrate. Evidence for
      the biomobilization of elements by these endolithic lichens was found. L.
      cancriformis was observed to accumulate substantial amounts of calcium-rich
      biominerals. The combined approach proposed is useful for mapping the
      distribution of endolithic lichens and analysing the processes that occur in
      their microscopic environment.

PMID- 15720633
TI  - Evaluation of natural and synthetic stimulants of plant immunity by microarray
      technology.
AB  - Induction of local defence, as well as systemic resistance, of plants is
      associated with transcriptional reprogramming. Here we report on defence gene
      induction by natural and synthetic stimulants of plant immunity. Gene expression
      changes in Arabidopsis thaliana were monitored in response to several plant
      immunity stimulants (plant activators) using Northern blotting and an application
      based array representing c. 750 genes involved in several aspects of plant
      defence and/or plant stress. The commercial plant activators Bio-S, Neudo-Vital
      and PRORADIX have been shown to induce systemic resistance. Here, Neudo-Vital,
      PRORADIX and Bio-S treatment induced different patterns of salicylic acid (SA)
      and jasmonic acid (JA) accumulation. Gene induction by these plant activators
      proved to be very complex. Rather than simply mimicking one of the known defence
      pathways induced by SA or JA, the response to the plant activators showed aspects
      of both major defence systems. A general feature was the transient activation of
      JA biosynthesis genes, combined with a much more sustained SA-associated defence
      gene induction. Our results demonstrate that plant immunity stimulants activate
      systemic immunity at the transcriptional level, and they provide insight into the
      coordinated transcriptional regulation of several classes of plant defence genes.

PMID- 15720634
TI  - Is variation in susceptibility to Phytophthora ramorum correlated with population
      genetic structure in coast live oak (Quercus agrifolia)?
AB  - California coastal woodlands are suffering severe disease and mortality as a
      result of infection from Phytophthora ramorum. Quercus agrifolia is one of the
      major woodland species at risk. This study investigated within- and among
      population variation in host susceptibility to inoculation with P. ramorum and
      compared this with population genetic structure using molecular markers.
      Susceptibility was assessed using a branch-cutting inoculation test. Trees were
      selected from seven natural populations in California. Amplified fragment length
      polymorphism molecular markers were analysed for all trees used in the trials.
      Lesion sizes varied quantitatively among individuals within populations, with up
      to an eightfold difference. There was little support for population differences
      in susceptibility. Molecular structure also showed a strong within-population,
      and weaker among-population, pattern of variation. Our data suggest that
      susceptibility of Q. agrifolia to P. ramorum is variable and is under the control
      of several gene loci. This variation exists within populations, so that less
      susceptible local genotypes may provide the gene pool for regeneration of
      woodlands where mortality is high.

PMID- 15720635
TI  - Endocytosis of Xanthomonas campestris pathovar campestris lipopolysaccharides in
      non-host plant cells of Nicotiana tabacum.
AB  - The specific recognition of phytopathogenic bacteria by plant cells is generally
      mediated by a number of signal molecules. The elicitor-active lipopolysaccharides
      (LPS) of the phytopathogenic bacterium Xanthomonas campestris pv. campestris
      (X.c.c) are recognized by its non-host plant Nicotiana tabacum (N.t.). This LPS
      was purified and labelled with fluorescein isothiocyanate (FITC) for monitoring
      the fate of these signal molecules in intact plant cells of tobacco. In this
      study we were able to show that the so-labelled LPS rapidly bound to the cell
      wall and was then internalized into the cells in a temperature- and energy
      dependent way. This uptake of LPS could be outcompeted by the addition of an
      excess of unlabelled LPS. Furthermore, it was blocked by amantadine, an inhibitor
      of receptor-mediated endocytosis of mammalian cells. Immunolocalization
      experiments showed for the first time a significant co-localization of the LPS
      elicitor with endosomal structures using an anti-Ara6 antibody. These
      observations suggest specific endocytosis of LPS(X.c.c.) into tobacco cells. The
      possibility for a receptor-mediated endocytosis comparable to the mammalian
      system will be discussed.

PMID- 15720636
TI  - Wheat leaf photosynthesis loss due to leaf rust, with respect to lesion
      development and leaf nitrogen status.
AB  - In wheat (Triticum aestivum cv. Soissons) plants grown under three different
      fertilisation treatments, we quantified the effect of leaf rust (Puccinia
      triticina) on flag leaf photosynthesis during the whole sporulation period.
      Bastiaans' model: Y = (1 - x)beta was used to characterize the relationship
      between relative leaf photosynthesis (Y) and disease severity (x). The evolution
      of the different types of symptoms induced by the pathogen (sporulating,
      chlorotic and necrosed tissues) was evaluated using image analysis. The beta
      values varied from 2 to 11, 1.4-2, and 0.8-1 during the sporulation period, when
      considering the proportion of sporulating, sporulating + necrotic, and total
      diseased area, respectively. Leaf nitrogen (N) content did not change the effect
      of the disease on host photosynthesis. We concluded that leaf rust has no global
      effect on the photosynthesis of the symptomless parts of the leaves and that the
      large range in the quantification of leaf rust effect on the host, which is found
      in the literature, can be accounted for by considering the different symptom
      types. We discuss how our results could improve disease assessments and damage
      prediction in a wheat crop.

PMID- 15720637
TI  - The intercellular biotrophic leaf pathogen Cymadothea trifolii locally degrades
      pectins, but not cellulose or xyloglucan in cell walls of Trifolium repens.
AB  - The intercellular ascomycetous pathogen Cymadothea trifolii, causing sooty blotch
      of clover, proliferates within leaves of Trifolium spp. and produces a complex
      structure called interaction apparatus (IA) in its own hyphae. Opposite the IA
      the plant plasmalemma invaginates to form a bubble. Both structures are connected
      by a tube with an electron-dense sheath. Using immunocytochemistry on high
      pressure frozen and freeze-substituted samples, we examined several plant and
      fungal cell wall components, including those in new host wall appositions at the
      interaction site, as well as a fungal polygalacturonase. Within the tube linking
      IA and host bubble, labelling was obtained for cellulose and xyloglucan but not
      for rhamnogalacturonan-I and homogalacturonans. The IA labelled for chitin and
      beta-1,3-glucans, and for a fungal polygalacturonase. Plant wall appositions
      reacted with antibodies against callose, xyloglucans and rhamnogalacturonan-I.
      Cymadothea trifolii partly degrades the host cell wall. Structural elements
      remain intact, but the pectin matrix is dissolved. A fungal polygalacturonase
      detected in the IA is probably a key factor in this process. Owing to the
      presence of chitin and beta-1,3-glucans, the IA itself is considered an
      apoplastic compartment.

PMID- 15720638
TI  - Arbuscular mycorrhizal fungi reveal distinct patterns of anastomosis formation
      and hyphal healing mechanisms between different phylogenic groups.
AB  - The significance of anastomosis formation and the hyphal healing mechanism (HHM)
      for functionality and integrity of the arbuscular mycorrhizal (AM) fungal
      mycelial network remains poorly documented. Four Glomeraceae and three
      Gigasporaceae were cultured monoxenically. Anastomosis formation was assessed
      using the grid line method, while HHM was time-lapse monitored. In intact
      mycelial networks, the number of anastomosis per hyphal length was higher for
      Glomeraceae than for Gigasporaceae strains. Glomeraceae strains studied always
      formed anastomosis between different hyphae, whereas anastomosis in the
      Gigasporaceae more often concerned hyphal bridges within the same hyphae. In both
      families the HHM corresponded to a four-step process; first septum formation;
      second initiation of growing hyphal tips (GHTs); third GHT elongation,
      orientation and contact; and fourth GHT fusion and cytoplasmic/protoplasmic flux
      re-establishment. These four steps differentiated Glomeraceae from Gigasporaceae.
      The type and number of anastomosis per hyphal length, and the HHM differed
      considerably between Glomeraceae and Gigasporaceae families representing a
      supplementary character that distinguishes these two families and may be of
      significance in ecological studies of AM fungi.

PMID- 15720639
TI  - Community structure of arbuscular mycorrhizal fungi at different soil depths in
      extensively and intensively managed agroecosystems.
AB  - The vertical distribution of spores of arbuscular mycorrhizal fungi (AMF) was
      investigated in soil profiles of extensively and intensively managed
      agroecosystems, including two permanent grasslands, a vineyard and two
      continuously mono-cropped maize fields. The number of AMF spores decreased with
      increasing soil depth--most drastically in the grasslands and the vineyard--but
      there was a large diversity of AMF species even in the deepest soil layers (50-70
      cm). This was particularly striking in the maize fields where the highest species
      numbers were found below ploughing depth. Some species sporulated mainly, or
      exclusively, in the deep soil layers, others mainly in the top layers. Soil
      samples were used to inoculate trap cultures. Up to 18 months after inoculation,
      there was no conspicuous difference in the species composition among the trap
      cultures representing different soil depths, and only a weak match to the species
      composition determined by analysis of field samples. Our results indicate that
      the AMF communities in deep soil layers are surprisingly diverse and different
      from the topsoil. Thus, deep soil layers should be included in studies to get a
      complete picture of AMF diversity.

PMID- 15720640
TI  - Genetic structure of Cenococcum geophilum populations in primary successional
      volcanic deserts on Mount Fuji as revealed by microsatellite markers.
AB  - Polymorphic simple sequence repeat (SSR) markers were used to investigate the
      genetic structure in a Cenococcum geophilum population associated with Salix
      reinii in an early successional volcanic desert at Gotenba, on the south-eastern
      slope of Mount Fuji in Japan, and in three other populations associated with the
      same host at more developed sites on the mountain, one at Fujinomiya and two at
      Subashiri. The genotype richness of C. geophilum tended to be higher in more
      developed vegetation patches as well as in more developed sites, suggesting that
      genotype richness increased with advanced succession because new genotypes might
      have been introduced into these sites over time. High genotypic similarity was
      observed between the Gotenba and Fujinomiya populations but not between the
      Gotenba and Subashiri populations, suggesting that C. geophilum genotypes in
      Gotenba were introduced from the direction of Fujinomiya. Genotypes in the
      Gotenba population were clearly distinguishable into two groups. The absence of
      any intermediate genotype suggests the absence of frequent recombination in this
      C. geophilum population associated with early successional vegetation.

PMID- 15720641
TI  - Pine microsatellite markers allow roots and ectomycorrhizas to be linked to
      individual trees.
AB  - Linking roots and ectomycorrhizas (EcM) to individual host trees in the field is
      required to test whether individual trees support different ectomycorrhizal
      communities. Here we describe a method that identifies the source of EcM roots by
      PCR of polymorphic pine nuclear microsatellite loci using fluorescently labelled
      primers and high-throughput fragment analysis. ITS-PCR can also be performed on
      the same EcM DNA extract for fungal identification. The method was tested on five
      neighbouring Scots pine (Pinus sylvestris var scotica) trees in native woodland.
      Successful host tree identification from DNA extracts of EcM root tips was
      achieved for 93% of all root fragments recovered from soil cores. It was
      estimated that each individual mature pine sampled was colonised by between 15
      and 19 EcM fungi. The most abundant fungal species were found on all five trees,
      and within the constraints of the sampling scheme, no differences between trees
      in EcM fungal community structure or composition were detected.

PMID- 15720642
TI  - Evidence of species interactions within an ectomycorrhizal fungal community.
AB  - Ectomycorrhizal fungal communities can be structured by abiotic and biotic
      factors. Here, we present evidence for community structuring by species
      interactions. We sampled ectomycorrhizas and forest floor seven times during a 13
      month period. The presence of various ectomycorrhizal fungal species was
      determined for each sample, and species co-occurrence analyses were performed.
      For both ectomycorrhizas and forest floor samples there was significantly less co
      occurrence among species within the community than expected by chance, mostly
      because of negative associations involving Cenococcum geophilum or Clavulina
      cinerea. For some species pairs, there was significantly more co-occurrence than
      expected by chance. Both nitrogen and tannin additions to the forest floor
      altered some interactions among species. The causes of these nonrandom
      distributions are currently unknown. Future investigations on competition,
      antibiosis, parasitism and facilitation among ectomycorrhizal fungal species
      appear to be warranted.

PMID- 15720643
TI  - Ectomycorrhizal symbiosis affects functional diversity of rhizosphere fluorescent
      pseudomonads.
AB  - Here we characterized the effect of the ectomycorrhizal symbiosis on the
      genotypic and functional diversity of soil Pseudomonas fluorescens populations
      and analysed its possible consequences in terms of plant nutrition, development
      and health. Sixty strains of P. fluorescens were isolated from the bulk soil of a
      forest nursery, the ectomycorrhizosphere and the ectomycorrhizas of the Douglas
      fir (Pseudostuga menziesii) seedlings-Laccaria bicolor S238N. They were
      characterized in vitro with the following criteria: ARDRA, phosphate
      solubilization, siderophore, HCN and AIA production, genes of N2-fixation and
      antibiotic synthesis, in vitro confrontation with a range of phytopathogenic and
      ectomycorrhizal fungi, effect on the Douglas fir-L. bicolor symbiosis. For most
      of these criteria, we demonstrated that the ectomycorrhizosphere significantly
      structures the P. fluorescens populations and selects strains potentially
      beneficial to the symbiosis and to the plant. This prompts us to propose the
      ectomycorrhizal symbiosis as a true microbial complex where multitrophic
      interactions take place. Moreover it underlines the fact that this symbiosis has
      an indirect positive effect on plant growth, via its selective pressure on
      bacterial communities, in addition to its known direct positive effect.

PMID- 15720644
TI  - Reproductive consequences of interactions between clonal growth and sexual
      reproduction in Nymphoides peltata: a distylous aquatic plant.
AB  - Distyly is a sexual polymorphism in which plant populations contain two floral
      morphs differing in morphology and physiology. The dimorphism serves to promote
      animal-mediated cross-pollination between the floral morphs. Clonal propagation
      can interfere with the functioning of distyly by compromising intermorph
      pollinations, resulting in reduced fertility. Here, we investigate the relations
      between clonal growth and sexual reproduction in the aquatic macrophyte
      Nymphoides peltata (Menyanthaceae). Surveys of morph representation in 30
      populations from five regions of China revealed that most populations exhibited
      strongly biased morph ratios and 30% contained a single floral morph.
      Experimental pollinations indicate that N. peltata possesses a strong dimorphic
      incompatibility system preventing self and intramorph fertilizations. An
      experiment involving the manipulation of morph ratios in an experimental
      population and an investigation in a natural population with strong morph
      substructure both provided evidence that compatible pollen dilution limits
      fertility. Despite constraints on the functioning of distyly in N. peltata we
      found no evidence for evolutionary changes to the heterostylous syndrome, as
      reported in Nymphoides, including populations of N. peltata in other parts of its
      geographical range.

PMID- 15720646
TI  - Threshold models applied to seed germination ecology.

PMID- 15720647
TI  - Understanding a flammable planet - climate, fire and global vegetation patterns.

PMID- 15720648
TI  - Are liverworts imitating mycorrhizas?

PMID- 15720649
TI  - What have we learned from 15 years of free-air CO2 enrichment (FACE)? A meta
      analytic review of the responses of photosynthesis, canopy properties and plant
      production to rising CO2.
AB  - Free-air CO(2) enrichment (FACE) experiments allow study of the effects of
      elevated [CO(2)] on plants and ecosystems grown under natural conditions without
      enclosure. Data from 120 primary, peer-reviewed articles describing physiology
      and production in the 12 large-scale FACE experiments (475-600 ppm) were
      collected and summarized using meta-analytic techniques. The results confirm some
      results from previous chamber experiments: light-saturated carbon uptake, diurnal
      C assimilation, growth and above-ground production increased, while specific leaf
      area and stomatal conductance decreased in elevated [CO(2)]. There were
      differences in FACE. Trees were more responsive than herbaceous species to
      elevated [CO(2)]. Grain crop yields increased far less than anticipated from
      prior enclosure studies. The broad direction of change in photosynthesis and
      production in elevated [CO(2)] may be similar in FACE and enclosure studies, but
      there are major quantitative differences: trees were more responsive than other
      functional types; C(4) species showed little response; and the reduction in plant
      nitrogen was small and largely accounted for by decreased Rubisco. The results
      from this review may provide the most plausible estimates of how plants in their
      native environments and field-grown crops will respond to rising atmospheric
      [CO(2)]; but even with FACE there are limitations, which are also discussed.

PMID- 15720650
TI  - In touch: plant responses to mechanical stimuli.
AB  - Perception and response to mechanical stimuli are likely essential at the
      cellular and organismal levels. Elaborate and impressive touch responses of
      plants capture the imagination as such behaviors are unexpected in otherwise
      often quiescent creatures. Touch responses can turn plants into aggressors
      against animals, trapping and devouring them, and enable flowers to be active in
      ensuring crosspollination and shoots to climb to sunlit heights. Morphogenesis is
      also influenced by mechanical perturbations, including both dynamic environmental
      stimuli, such as wind, and constant forces, such as gravity. Even individual
      cells must sense turgor and wall integrity, and subcellular organelles can
      translocate in response to mechanical perturbations. Signaling molecules and
      hormones, including intracellular calcium, reactive oxygen species, octadecanoids
      and ethylene, have been implicated in touch responses. Remarkably, touch-induced
      gene expression is widespread; more than 2.5% of Arabidopsis genes are rapidly up
      regulated in touch-stimulated plants. Many of these genes encode calcium-binding,
      cell wall modifying, defense, transcription factor and kinase proteins. With
      these genes as tools, molecular genetic methods may enable elucidation of
      mechanisms of touch perception, signal transduction and response regulation.

PMID- 15720651
TI  - Genome conflict in the gramineae.
AB  - The genomes of grasses and cereals include a diverse and large collection of
      selfish genetic elements, many of which are fossil relics of ancient origin. Some
      of these elements are active and, because of their selfish nature and the way in
      which they exist to perpetuate themselves, they cause a conflict for genomes both
      within and between species in hybrids and allopolyploids. The conflict arises
      from how the various elements may undergo 'drive', through transposition,
      centromere and neocentromere drive, and in mitotic and meiotic drive processes in
      supernumerary B chromosomes. Experimental and newly formed hybrids and
      polyploids, where new combinations of genomes are brought together for the first
      time, find themselves sharing a common nuclear and cytoplasmic environment, and
      they can respond with varying degrees of instability to adjust to their new
      partnerships. B chromosomes are harmful to fertility and to the physiology of the
      cells and plants that carry them. In this review we take a broad view of genome
      conflict, drawing together aspects arising from a range of genetic elements that
      have not hitherto been considered in their entirety, and we find some common
      themes linking these various elements in their activities.

PMID- 15720652
TI  - Hybrid speciation in plants: new insights from molecular studies.
AB  - Abrupt speciation through interspecific hybridisation is an important mechanism
      in angiosperm evolution. Flowering plants therefore offer excellent opportunities
      for studying genetic processes associated with hybrid speciation. Novel molecular
      approaches are now available to examine these processes at the level of both
      genome organization and gene expression - transcriptomics. Here, we present an
      overview of the molecular technologies currently used to study hybrid speciation
      and how they are providing new insights into this mode of speciation in flowering
      plants. We begin with an introduction to hybrid speciation in plants, followed by
      a review of techniques, such as isozymes and other markers, which have been used
      to study hybrid species in the past. We then review advances in molecular
      techniques that have the potential to be applied to studies of hybrid species,
      followed by an overview of the main genomic and transcriptomic changes suspected,
      or known, to occur in newly formed hybrids, together with commentary on the
      application of advanced molecular tools to studying these changes.

PMID- 15720653
TI  - The Arabidopsis CDC25 induces a short cell length when overexpressed in fission
      yeast: evidence for cell cycle function.
AB  - The putative mitotic inducer gene, Arath;CDC25 cloned in Arabidopsis thaliana,
      was screened for cell cycle function by overexpressing it in Schizosaccharomyces
      pombe (fission yeast). The expression pattern of Arath;CDC25 was also examined in
      different tissues of A. thaliana. Fission yeast was transformed with plasmids
      pREP1 and pREP81 with the Arath;CDC25 gene under the control of the thiamine
      repressible nmt promoter. Using reverse transcription-polymerase chain reaction
      (RT-PCR), the expression of Arath;CDC25 was examined in seedlings, flower buds,
      mature leaves and stems of A. thaliana; actin (ACT2) was used as a control. In
      three independent transformants of fission yeast, cultured in the absence of
      thiamine (T), pREP1::Arath;CDC25 induced a highly significant reduction in
      mitotic cell length compared with wild type, pREP::Arath;CDC25 +T, and empty
      vector (pREP1 +/- T). The extent of cell shortening was greater using the
      stronger pREP1 compared with the weaker pREP81. However, Arath;CDC25 was
      expressed at low levels in all tissues examined. The data indicate that
      Arath;CDC25 can function as a mitotic accelerator in fission yeast. However,
      unlike other plant cell cycle genes, expression of Arath;CDC25 was not enhanced
      in rapidly dividing compared with non-proliferative Arabidopsis tissues.

PMID- 15720654
TI  - Genome-wide identification of touch- and darkness-regulated Arabidopsis genes: a
      focus on calmodulin-like and XTH genes.
AB  - We sought to gain insight into functions potentially altered by
      mechanostimulation and investigate the relationship between touch and darkness
      responses. Microarrays and quantitative RT-PCR were conducted to identify genes
      and analyze behaviors of calmodulin-like (CML) and xyloglucan
      endotransglucosylase/hydrolase (XTH) genes. Strikingly, 589 genes had touch
      inducible expression; 171 had reduced expression. Darkness increased expression
      of 461 genes and decreased expression of 72 genes. Over half of the touch
      inducible genes resembled the TCH genes in that they were also up-regulated by
      darkness; 67% of those darkness-inducible were also touch inducible. Expression
      of 12 CMLs and four XTHs was elevated by touch; three XTHs had reduced
      expression. In darkness-treated plants, 10 CMLs and nine XTHs had increased
      expression and one XTH was repressed. Over 2.5% of total genes were touch
      inducible. Many were also darkness up-regulated, consistent with the hypothesis
      that these stimuli have partially overlapping signal transduction pathways.
      Regulated gene identities suggest that calcium and kinase signaling, wall
      modification, disease resistance and downstream transcriptional responses may be
      altered in response to mechanostimulation or darkness.

PMID- 15720655
TI  - Changes in the light sensitivity of buried Polygonum aviculare seeds in relation
      to cold-induced dormancy loss: development of a predictive model.
AB  - The effect of cold (stratification) temperature on changes in the sensitivity of
      Polygonum aviculare seeds to light was investigated. Seeds buried in pots were
      stored under stratification temperatures (1.6, 7 and 12 degrees C) for 137 d.
      Seeds exhumed at regular intervals during storage were exposed to different light
      treatments. Germination responses obtained for seeds exposed to different light
      treatments and stratification temperatures were used to develop a model to
      predict the sensitivity of buried seeds to light. Seed sensitivity to light
      increased as dormancy loss progressed, showing the successive acquisition of low
      fluence responses (LFR), very low-fluence responses (VLFR), and the loss of the
      light requirement for germination for a fraction of the seed population. These
      changes were inversely correlated to stratification temperature, allowing the use
      of a thermal time index to relate observed changes in seed light sensitivity to
      stratification temperature. The rate of increase in sensitivity of P. aviculare
      seeds to light during stratification is inversely correlated to soil temperature,
      and these changes in light sensitivity could be predicted in relation to
      temperature using thermal-time models.

PMID- 15720656
TI  - Irradiance and temperature affect the competitive interference of blackberry on
      the physiology of European beech seedlings.
AB  - The potential negative influence of competition from early successional species
      like blackberry (Rubus fruticosus) may be decisive for the natural regeneration
      success of drought-sensitive beech (Fagus sylvatica), especially in the light of
      climate change. With a split plot glasshouse experiment, we investigated the
      influence of two air temperature and irradiance levels on the competitive
      interference of blackberry on the water, nitrogen (N) and carbon (C) balance of
      beech seedlings under moderate drought. When increased temperature was
      accompanied by low irradiance the biomass, root-to-shoot ratio, N uptake and
      assimilation rates of blackberry were lower compared with beech, either grown
      alone or with blackberry. By contrast, when elevated temperature and high
      irradiance were combined, the root-to-shoot ratio and specific N uptake rate of
      blackberry were substantially increased, while the N acquisition of beech was
      impaired. Under lower temperature, with either full light or shade, the presence
      of blackberry had no significant effects on beech, for almost all tested
      parameters. Under elevated air temperature beech was impaired by the presence of
      blackberry at high irradiance. These findings emphasize the interacting effects
      between environmental factors and competition on the establishment of beech
      regeneration, which should be considered for future forest management in the
      frame of climate change.

PMID- 15720657
TI  - Nondestructive assessment of leaf chemistry and physiology through spectral
      reflectance measurements may be misleading when changes in trichome density co
      occur.
AB  - Reflectance indices are frequently used for the nondestructive assessment of leaf
      chemistry, especially pigment content, in environmental or developmental studies.
      Since reflectance spectra are influenced by trichome density, and trichome
      density displays a considerable phenotypic plasticity, we asked whether this
      structural parameter could be a source of variation in the values of the most
      commonly used indices. Trichome density was manipulated in detached leaves of
      three species having either peltate (Olea europaea and Elaeagnus angustifolius)
      or tubular (Populus alba) trichomes by successive removal of hairs. After each
      dehairing step, trichome density was determined by light or scanning electron
      microscopy and reflectance spectra were obtained with a diode-array spectrometer.
      Although species-specific differences were evident, most of the indices were
      considerably affected even at low trichome densities. In general, the less
      affected indices were those using wavebands within the visible spectral region.
      The index that could be safely used even at very high hair densities in all
      species was the red edge index (lambda(RE)) for chlorophyll. The results indicate
      that changes in reflectance indices should be interpreted cautiously when
      concurrent changes in trichome density are suspected. In this case, the red edge
      for chlorophyll content may be the index of choice.

PMID- 15720658
TI  - Delay of Iris flower senescence by protease inhibitors.
AB  - Visible senescence of the flag tepals in Iris x hollandica (cv. Blue Magic) was
      preceded by a large increase in endoprotease activity. Just before visible
      senescence about half of total endoprotease activity was apparently due to
      cysteine proteases, somewhat less than half to serine proteases, with a minor
      role of metalloproteases. Treatment of isolated tepals with the purported serine
      protease inhibitors AEBSF [4-(2-aminoethyl)-benzenesulfonyl fluoride] or DFP
      (diisopropyl-fluorophosphate) prevented the increase in endoprotease activity and
      considerably delayed or prevented the normal senescence symptoms. The specific
      cysteine protease-specific E-64d reduced maximum endoprotease activity by 30%,
      but had no effect on the time to visible senescence. Zinc chloride and aprotinin
      reduced maximum endoprotease activity by c. 50 and 40%, respectively, and
      slightly delayed visible senescence. A proteasome inhibitor (Z-leu-leu-Nva-H)
      slightly delayed tepal senescence, which indicates that protein degradation in
      the proteasome may play a role in induction of the visible senescence symptoms.
      It is concluded that visible senescence is preceded by large-scale protein
      degradation, which is apparently mainly due to cysteine- and serine protease
      activity, and that two (unspecific) inhibitors of serine proteases considerably
      delay the senescence symptoms.

PMID- 15720659
TI  - Organic acids promote the uptake of lanthanum by barley roots.
AB  - Organic acids play an important role in metal uptake by, and accumulation in,
      plants. However, the relevant mechanisms remain obscure. Acetic, malic and citric
      acids increased the uptake of lanthanum (La) by barley (Hordeum vulgare) roots
      and enhanced La content in shoots under hydroponic conditions. Concentration
      dependent net La influx in the absence and presence of organic acids yielded
      nonsaturating kinetic curves that could be resolved into linear and saturable
      components. The saturable component followed Michaelis-Menten kinetics. The K(m)
      values were similar; however, the V(max) values in the presence of acetic, malic
      and citric acids were 4.3, 2.8, 1.5-times that of the control, respectively.
      Enhanced uptake of La by organic acids was mediated mainly, but not solely, by
      Ca(2+) channels. X-ray absorption spectroscopic techniques provided evidence of
      La-oxygen environment and established that La(III) was coordinated to 11 oxygen
      atoms that are likely to be involved in the binding of La(III) to barley roots
      via carboxylate groups and hydration of La(III).

PMID- 15720660
TI  - Rapid decline in nitrate uptake and respiration with age in fine lateral roots of
      grape: implications for root efficiency and competitive effectiveness.
AB  - Changes in function as an individual root ages has important implications for
      understanding resource acquisition, competitive ability and optimal lifespan.
      Both nitrate uptake and respiration rates of differently aged fine roots of grape
      (Vitis rupestris x V. riparia cv. 3309 C) were measured. The resulting data were
      then used to simulate nitrate uptake efficiency and nutrient depletion as a
      function of root age. Both nitrate uptake and root respiration declined
      remarkably quickly with increasing root age. The decline in both N uptake and
      root respiration corresponded with a strong decline in root N concentration,
      suggesting translocation of nitrogen out of the roots. For simulations where no
      nutrient depletion occurs at the root surface, daily uptake efficiency was
      maximal at root birth and lifetime nitrate uptake efficiency slowly increased as
      the roots aged. Simulations of growth of roots into unoccupied soil using a
      solute transport model indicated the advantage of high uptake capacity in new
      roots under competitive conditions where nitrate availability is very transitory.

PMID- 15720661
TI  - Thlaspi caerulescens on nonmetalliferous soil in Luxembourg: ecological niche and
      genetic variation in mineral element composition.
AB  - Forty-seven populations of Thlaspi caerulescens in Luxembourg were characterised
      for population size, soil mineral element composition and other habitat
      characteristics. Foliar concentrations of eight elements were assessed in 15
      populations in the field and in eight populations cultivated in zinc (Zn)-cadmium
      (Cd)-nickel (Ni)-enriched soil. T. caerulescens favoured stony soil developed on
      steep, south-facing Emsian shale outcrops. All soil samples were
      nonmetalliferous. Soil pH ranged from 4.2 to 6.9. Field-growing plants had very
      high concentrations of heavy metals in the leaves (Zn, 3000-13 000 mg kg(-1); Cd,
      11-44 mg kg(-1); Ni, 38-473 mg kg(-1)). Positive soil-plant correlations existed
      for Zn and Mn. In cultivation, significant genetic variation was found for
      biomass and six of eight mineral elements. For Cd and Zn, variation range among
      48 half-sib families was two-fold (Cd, 183-334 mg kg(-1); Zn, 8030-16 295 mg kg(
      1)). Most of the variation occurred among populations, consistent with the
      selfing mating system of those populations. There was a tight Zn-Cd genetic
      correlation (r = +0.83, P < 0.0001). The significance of the results to the
      conservation of T. caerulescens in Luxembourg is briefly discussed.

PMID- 15720662
TI  - Purification and characterization of a fructosyltransferase from onion bulbs and
      its key role in the synthesis of fructo-oligosaccharides in vivo.
AB  - A fructosyltransferase that transfers the terminal (2 --> 1)-beta-linked D
      fructosyl group of fructo-oligosaccharides (1(F)(1-beta-D-fructofuranosyl)(n)
      sucrose, n >/= 1) to HO-6 of the glucosyl residue and HO-1 of the fructosyl
      residue of similar saccharides (1(F)(1-beta-D-fructofuranosyl)(m) sucrose, m >/=
      0) has been purified from an extract of the bulbs of onion (Allium cepa).
      Successive column chromatography using DEAE-Sepharose CL-6B, Toyopearl HW65,
      Toyopearl HW55, DEAE-Sepharose CL-6B (2nd time), Sephadex G-100, Concanavalin A
      Sepharose, and Toyopearl HW-65 (2nd time) were applied for protein purification.
      The general properties of the enzyme, were as follows: molecular masses of 66 kDa
      (gel filtration chromatography), and of 52 kDa and 25 kDa (SDS-PAGE); optimum pH
      of c. 5.68, stable at 20-40 degrees C for 15 min; stable in a range of pH 5.30
      6.31 at 30 degrees C for 30 min, inhibited by Hg(2+), Ag(+), p
      chloromercuribenzoic acid (p-CMB) and sodium dodecyl sulfate (SDS), activated by
      sodium deoxycholate, Triton X-100 and Tween-80. The amino acid sequence of the N
      terminus moiety of the 52-kDa polypeptide was
      ADNEFPWTNDMLAWQRCGFHFRTVRNYMNDPSGPMYYKGWYHLFYQHNKDFAYXG and the amino acid
      sequence from the N-terminus of the 25-kDa polypeptide was
      ADVGYXCSTSGGAATRGTLGPFGLL VLANQDLTENTATYFYVSKGTDGALRTHFCQDET. The enzyme
      tentatively classified as fructan: fructan 6(G)-fructosyltransferase (6G-FFT).
      The enzyme is proposed to play an important role in the synthesis of inulin and
      inulinneo-series fructo-oligosaccharides in onion bulbs.

PMID- 15720663
TI  - The global distribution of ecosystems in a world without fire.
AB  - This paper is the first global study of the extent to which fire determines
      global vegetation patterns by preventing ecosystems from achieving the potential
      height, biomass and dominant functional types expected under the ambient climate
      (climate potential). To determine climate potential, we simulated vegetation
      without fire using a dynamic global-vegetation model. Model results were tested
      against fire exclusion studies from different parts of the world. Simulated
      dominant growth forms and tree cover were compared with satellite-derived land-
      and tree-cover maps. Simulations were generally consistent with results of fire
      exclusion studies in southern Africa and elsewhere. Comparison of global 'fire
      off' simulations with landcover and treecover maps show that vast areas of humid
      C(4) grasslands and savannas, especially in South America and Africa, have the
      climate potential to form forests. These are the most frequently burnt ecosystems
      in the world. Without fire, closed forests would double from 27% to 56% of
      vegetated grid cells, mostly at the expense of C(4) plants but also of C(3)
      shrubs and grasses in cooler climates. C(4) grasses began spreading 6-8 Ma, long
      before human influence on fire regimes. Our results suggest that fire was a major
      factor in their spread into forested regions, splitting biotas into fire tolerant
      and intolerant taxa.

PMID- 15720664
TI  - Lethal effects of experimental warming approximating a future climate scenario on
      southern African quartz-field succulents: a pilot study.
AB  - Here we examine the response of succulents in a global biodiversity hot spot to
      experimental warming consistent with a future African climate scenario. Passive
      daytime warming (averaging 5.5 degrees C above ambient) of the natural vegetation
      was achieved with 18 transparent hexagonal open-top chamber arrays randomized in
      three different quartz-field communities. After 4-months summer treatment, the
      specialized-dwarf and shrubby succulents displayed between 2.1 and 4.9 times
      greater plant and canopy mortalities in the open-top chambers than in the control
      plots. Those surviving in cooler ventilated areas and shaded refuges in the
      chambers had lower starch concentrations and water contents; the shrubby
      succulents also exhibited diminished chlorophyll concentrations. It is concluded
      that current thermal regimes are likely to be closely proximate to tolerable
      extremes for many endemic succulents in the region, and that anthropogenic
      warming could significantly exceed their thermal thresholds. Further
      investigation is required to elucidate the importance of associated moisture
      deficits in these warming experiments, a potential consequence of supplementary
      (fog and dew) precipitation interception by open-top chambers and higher
      evaporation therein, on plant mortalities.

PMID- 15720665
TI  - Components of ecosystem evaporation in a temperate coniferous rainforest, with
      canopy transpiration scaled using sapwood density.
AB  - Here we develop and test a method to scale sap velocity measurements from
      individual trees to canopy transpiration (E(c)) in a low-productivity, old-growth
      rainforest dominated by the conifer Dacrydium cupressinum. Further, E(c) as a
      component of the ecosystem water balance is quantified in relation to forest
      floor evaporation rates and measurements of ecosystem evaporation using eddy
      covariance (E(eco)) in conditions when the canopy was dry and partly wet. Thermal
      dissipation probes were used to measure sap velocity of individual trees, and
      scaled to transpiration at the canopy level by dividing trees into classes based
      on sapwood density and canopy position (sheltered or exposed). When compared with
      ecosystem eddy covariance measurements, E(c) accounted for 51% of E(eco) on dry
      days, and 22% of E(eco) on wet days. Low transpiration rates, and significant
      contributions to E(eco) from wet canopy evaporation and understorey transpiration
      (35%) and forest floor evaporation (25%), were attributable to the unique
      characteristics of the forest: in particular, high rainfall, low leaf area index,
      low stomatal conductance and low productivity associated with severe nutrient
      limitation.

PMID- 15720666
TI  - The Lipid A substructure of the Sinorhizobium meliloti lipopolysaccharides is
      sufficient to suppress the oxidative burst in host plants.
AB  - Medicago sativa (alfalfa), Medicago truncatula and Nicotiana tabacum cell
      suspension cultures, responding to elicitation with the production of reactive
      oxygen species (ROS), were used to analyse the suppressor (and elicitor) activity
      of lipopolysaccharides (LPS) of the symbiotic soil bacterium Sinorhizobium
      meliloti. In order to identify the epitopes of the LPS molecule recognized by the
      plant, S. meliloti mutants defective in LPS biosynthesis and hydrolytically
      obtained Lipid A were analysed for biological activity. Lipopolysaccharides
      isolated from Sinorhizobium meliloti mutants 6963 (altered core region) and L994
      (no long-chain fatty acid) showed the same ability to suppress the oxidative
      burst in host plant cell cultures as the wild-type LPS. Lipid A also displayed
      the same suppressor activity. By contrast, rhizobial LPS, but not Lipid A, was
      active as an inducer of the oxidative burst reaction in cell cultures of the
      nonhost Nicotiana tabacum. In host plants of Sinorhizobium meliloti the Lipid A
      part is sufficient to suppress the oxidative burst, but in non-host plants at
      least some sugars of the LPS core region are required to induce defence
      reactions.

PMID- 15720667
TI  - The liverwort Marchantia foliacea forms a specialized symbiosis with arbuscular
      mycorrhizal fungi in the genus Glomus.
AB  - Microscopic evidence suggests that fungi forming endosymbioses with liverworts in
      the Marchantiales are arbuscular mycorrhizal (AM) fungi from the Glomeromycota.
      Polymerase chain reaction amplification of ribosomal sequences confirmed that
      endophytes of the New Zealand liverwort, Marchantia foliacea, were members of the
      genus Glomus. Endophytes from two Glomus rDNA phylotypes were repeatedly isolated
      from geographically separated liverwort samples. Multiple phylotypes were present
      in the same liverwort patch. The colonizing Glomus species exhibited substantial
      internal transcribed spacer sequence variation within phylotypes. This work
      suggests that certain liverwort species may serve as a model for studying DNA
      sequence variation in colonizing AM phylotypes and specificity in AM-host
      relationships.

PMID- 15720668
TI  - Base cation stimulation of mycorrhization and photosynthesis of sugar maple on
      acid soils are coupled by foliar nutrient dynamics.
AB  - The nutritional benefits that mycorrhizal associations provide to plants may be
      constrained by acidic soil conditions resulting in decreased photosynthetic
      function. Sugar maple (Acer saccharum) and red maple (Acer rubrum) seedlings were
      grown on a native acidic (pH 4.1) soil both unamended and amended with base
      cations (pH 6.2). In a second study a fungicide treatment was included. Foliar
      nutrition, mycorrhizal colonization, photosynthesis and their relationships were
      assessed. On the native soil, red maple maintained higher levels of mycorrhizal
      colonization and photosynthesis than sugar maple but showed little response to
      base cation amendments. Mycorrhizal colonization and photosynthesis of sugar
      maple increased significantly in response to base cation amendments. Correlations
      were observed among mycorrhizal colonization, foliar nutrition and
      photosynthesis. The fungicide treatment indicated that 50% of the base cation
      induced increase in sugar maple photosynthesis was mycorrhiza related. The
      results suggest that base cation stimulation of mycorrhization and photosynthesis
      of sugar maple on acid soils are coupled by foliar nutrient dynamics. Red maple
      exhibits much less sensitivity to these same edaphic conditions.

PMID- 15720669
TI  - Mycorrhiza and root hairs in barley enhance acquisition of phosphorus and uranium
      from phosphate rock but mycorrhiza decreases root to shoot uranium transfer.
AB  - Some phosphate rocks (PR) contain high concentrations of uranium (U), which are
      potentially toxic via accumulation in soils and food chains, and plant uptake of
      U is likely to be influenced by characteristics of roots and associated
      microorganisms. The relative importance of root hairs and mycorrhiza in U uptake
      from PR was studied using a root hairless barley (Hordeum vulgare) mutant (Brb)
      and its wild type (WT). Both plant genotypes were grown in pots with Glomus
      intraradices BEG 87, or in the absence of mycorrhiza, and three P treatments were
      included: nil P, 2% (w/w) PR and 50 mg KH(2)PO(4)-P kg(-1) soil. Mycorrhiza
      markedly increased d. wts and P contents of Brb amended with nil P or PR, but
      generally depressed d. wts of WT plants, irrespective of P amendments. Mycorrhiza
      had contrasting effects on U contents in roots and shoots, in particular in Brb
      where mycorrhiza increased root U concentrations but decreased U translocation
      from roots to shoots. The experiment supports our understanding of arbuscular
      mycorrhiza as being multifunctional by not only improving the utilization of PR
      by the host plant but also by contributing to the phytostabilization of uranium.

PMID- 15720670
TI  - Transcript patterns associated with ectomycorrhiza development in Eucalyptus
      globulus and Pisolithus microcarpus.
AB  - Regulated gene expression is an important mechanism for controlling
      ectomycorrhizal symbiosis development. This study aimed to elucidate the
      coordination between development of mycorrhiza and the differential gene
      expression in both partners. We analysed RNA levels from sequential samples of
      symbiotic tissues of Eucalyptus globulus bicostata and the basidiomycete
      Pisolithus microcarpus progressing through ectomycorrhiza development using cDNA
      arrays. We derived groups of coordinately expressed genes using hierarchical and
      nonhierarchical clustering algorithms. Five major distinct temporal patterns of
      induction/repression were observed with distinct groups of early, middle-, and
      late-transcriptionally responsive genes to symbiosis formation. At earliest
      stages, the differentially expressed fungal genes included cell wall symbiosis
      regulated proteins, hydrophobins and mannoproteins, whereas transcripts coding
      for defense-related proteins were upregulated in plant tissues. Middle- and late
      transcriptionally responsive genes coded enzymes of glycolysis, tricarboxylic
      acid cycle and amino acid biosynthesis, as well as protein synthesis, hormone
      metabolism and signal transduction components. This investigation confirms and
      extends earlier results which found that changes in morphology associated with
      mycorrhizal development were accompanied by changes in transcript patterns, but
      no ectomycorrhiza-specific genes were detected.

PMID- 15720671
TI  - Growth and biomass of mycorrhizal mycelia in coniferous forests along short
      natural nutrient gradients.
AB  - Total fungal biomass, the biomass of ectomycorrhizal and ericoid mycorrhizal (EM
      + ErM), and arbuscular mycorrhizal (AM) fungi, as well as the production of EM
      and AM fungi, were estimated in coniferous forest soils along four natural
      nutrient gradients. Plant community changes, forest productivity, soil pH and N
      availability increase over relatively short distances (< 100 m) along the
      gradients. The amounts of the phospholipid fatty acid (PLFA) 18 : 2omega6,9 were
      used to estimate total fungi (not including AM), and the PLFA 16 : 1omega5 to
      estimate AM fungi in soil samples. The decrease in the PLFA 18 : 2omega6,9 during
      incubation of soils was used to estimate EM + ErM biomass. Production of AM and
      EM mycorrhiza was estimated using ingrowth mesh bags. Total fungal biomass was
      highest in soils with the lowest nutrient availability and tree productivity.
      Biomass of ErM + EM was also highest in these soils. We found tendencies that EM
      mycelial production was lowest in the soils with the highest nutrient
      availability and tree productivity. Production of AM fungi was highest in
      nutrient-rich soils with high pH. Our results suggest that mycorrhizal
      communities change from being ErM-, to EM- and finally to AM-dominated along
      these gradients. The observed changes in mycorrhizal type in the short nutrient
      gradients follow similar patterns to those suggested for altitudinal or
      latitudinal gradients over longer distances.

PMID- 15720672
TI  - Asymmetric evolution of duplicate genes encoding the CCAAT-binding factor NF-Y in
      plant genomes.
AB  - NF-Y is a ubiquitous CCAAT-binding factor composed of NF-YA, NF-YB and NF-YC.
      Multiple genes encoding NF-Y subunits have been identified in plant genomes. It
      remains unclear whether the duplicate genes underwent different evolutionary
      patterns. Likelihood-ratio tests were used to examine whether the amino acid
      substitution rates are the same between duplicate genes. The influences of
      selection on evolution were evaluated by comparing the conservative and radical
      amino acid substitution rates, as well as maximum-likelihood analysis. Some NF-YB
      and NF-YC duplicates showed significant evidence of asymmetric evolution but not
      the NF-YA duplicates. Most amino acid replacements in the NF-YB and NF-YC
      duplicates result in changes in hydropathy, polar requirement and polarity. The
      physicochemical changes in the sequences of NF-YB seem to be coupled to
      asymmetric divergence in gene function. Plant NF-Y genes have evolved in
      different patterns. Relaxed selective constraints following gene duplication are
      most likely responsible for the unequal evolutionary rates and distinct
      divergence patterns of duplicate NF-Y genes. Positive selection may have promoted
      amino acid hydropathy changes in the NF-YC duplicates.

PMID- 15720673
TI  - Repeated evolution of dioecy from androdioecy in Acer.
AB  - The evolution of breeding systems was studied in the genus Acer, with special
      attention to the origin of androdioecy and dioecy, using a phylogenetic approach.
      Parsimony and maximum-likelihood techniques were used to infer the ancestral
      character state and trends in the evolution of breeding systems. Information on
      breeding systems was obtained from the literature, and phylogenetic relationships
      were taken from three published phylogenies. Although a general trend from
      duodichogamy to dioecy through heterodichogamy has been proposed for the genus
      Acer, our results show that a general trend is not detected when phylogenetic
      relationships are taken into account. Dioecy appeared as a derived state that
      evolved at least three times and never reversed towards other states. Three
      different paths to dioecy have been followed in the genus Acer: from
      heterodichogamous androdioecy; from heterodichogamous trioecy; and from
      dichogamous subdioecy. Therefore, although the best documented cases of evolution
      of androdioecy indicate that this breeding system evolves from dioecy, in the
      genus Acer the opposite situation occurs (androdioecy leading to dioecy). Here we
      discuss the role of inbreeding avoidance and sexual specialization as selective
      forces driving the evolution of dioecy in the genus Acer.

PMID- 15720674
TI  - Morphometric analysis of root shape.
AB  - Alterations in the root shape in plant mutants indicate defects in hormonal
      signalling, transport and cytoskeleton function. To quantify the root shape, we
      introduced novel parameters designated vertical growth index (VGI) and horizontal
      growth index (HGI). VGI was defined as a ratio between the root tip ordinate and
      the root length. HGI was the ratio between the root tip abscissa and the root
      length. To assess the applicability of VGI and HGI for quantification of root
      shape, we analysed root development in agravitropic Arabidopsis mutants.
      Statistical analysis indicated that VGI is a sensitive morphometric parameter
      enabling detection of weak gravitropic defects. VGI dynamics were qualitatively
      similar in auxin-transport mutants aux1, pin2 and trh1, but different in the
      auxin-signalling mutant axr2. Analysis of VGI and HGI of roots grown on tilted
      plates showed that the trh1 mutation affected downstream cellular responses
      rather than perception of the gravitropic stimulus. All these tests indicate that
      the VGI and HGI analysis is a versatile and sensitive method for the study of
      root morphology.

PMID- 15720676
TI  - The nonmycorrhizal root--a strategy for survival in nutrient-impoverished soils.

PMID- 15720677
TI  - Ancient duplication of cereal genomes.

PMID- 15720678
TI  - A pioneer perspective on adaptation. Functional genomics of environmental
      adaptation in Populus: the 12th New Phytologist Symposium, Gatlinburg, TN, USA,
      October 2004.

PMID- 15720679
TI  - Guard cell metabolism and CO2 sensing.
AB  - In this review we concentrate on guard cell metabolism and CO2 sensing. Although
      a matter of some controversy, it is generally accepted that the Calvin cycle
      plays a minor role in stomatal movements. Recent data emphasise the importance of
      guard cell starch degradation and of carbon import from the guard cell apoplast
      in promoting and maintaining stomatal opening. Chloroplast maltose and glucose
      transporters appear to be crucial to the export of carbon from both guard and
      mesophyll cells. The way guard cells sense CO2 remains an unresolved question.
      However, a better understanding of the cellular events downstream from CO2
      sensing is emerging. We now recognise that there are common as well as unique
      steps in abscisic acid (ABA) and CO2 signalling pathways. For example, while ABA
      and CO2 both trigger increases in cytoplasmic free calcium, unlike ABA, CO2 does
      not promote a cytoplasmic pH change. Future advances in this area are likely to
      result from the increased use of techniques and resources, such as, reverse
      genetics, novel mutants, confocal imaging, and microarray analyses of the guard
      cell transcriptome.

PMID- 15720680
TI  - Legume nodule senescence: roles for redox and hormone signalling in the
      orchestration of the natural aging process.
AB  - Research on legume nodule development has contributed greatly to our current
      understanding of plant-microbe interactions. However, the factors that
      orchestrate root nodule senescence have received relatively little attention.
      Accumulating evidence suggests that redox signals contribute to the establishment
      of symbiosis and senescence. Although degenerative in nature, nodule senescence
      is an active process programmed in development in which reactive oxygen species
      (ROS), antioxidants, hormones and proteinases have key roles. Nodules have high
      levels of the redox buffers, ascorbate and glutathione, which are important in
      the nodulation process and in senescence. These metabolites decline with N
      fixation as the nodule ages but the resultant decrease in redox buffering
      capacity does not necessarily lead to enhanced ROS or oxidative stress. We
      propose models by which ROS and antioxidants interact with hormones such as
      abscisic acid in the orchestration of nodule senescence.

PMID- 15720681
TI  - Isotopic discrimination of zinc in higher plants.
AB  - * The extent of isotopic discrimination of transition metals in biological
      processes is poorly understood but potentially has important applications in
      plant and biogeochemical studies. * Using multicollector inductively coupled
      plasma (ICP) mass spectrometry, we measured isotopic fractionation of zinc (Zn)
      during uptake from nutrient solutions by rice (Oryza sativa), lettuce (Lactuca
      sativa) and tomato (Lycopersicon esculentum) plants. * For all three species, the
      roots showed a similar extent of heavy Zn enrichment relative to the nutrient
      solution, probably reflecting preferential adsorption on external root surfaces.
      By contrast, a plant-species specific enrichment of the light Zn isotope occurred
      in the shoots, indicative of a biological, membrane-transport controlled uptake
      into plant cells. The extent of the fractionation in the shoots further depended
      on the Zn speciation in the nutrient solution. * The observed isotopic depletion
      in heavy Zn from root to shoot (-0.13 to -0.26 per atomic mass unit) is
      equivalent to roughly a quarter of the total reported terrestrial variability of
      Zn isotopic compositions (c. 0.84 per atomic mass unit). Plant uptake therefore
      represents an important source of isotopic variation in biogeochemical cycling of
      Zn.

PMID- 15720682
TI  - Intersex inflorescences of Rumex acetosa demonstrate that sex determination is
      unique to each flower.
AB  - * A triploid intersex individual of the normally dioecious species Rumex acetosa
      showed extreme variability in gynoecium development. Analysis of the development
      and distribution of these flowers on inflorescences enabled insight to be gained
      into the mechanism of sex determination. * Floral phenotypes on intersex
      inflorescences were classified according to gynoecium development. Flower
      morphology was investigated by scanning electron and light microscopy. Organ
      identity gene expression in intersex floral primordia was assessed using in situ
      hybridization. * The distribution of the different floral phenotypes shows that
      each individual flower is determined separately, and that the phenotype of each
      flower is not influenced by its position on the inflorescence, or by the
      phenotype of neighbouring flowers. C-function gene expression persisted in
      gynoecia that had ceased development. * Gynoecium development in mutant flowers
      resembled the phenotype of the Arabidopsis mutant ettin and suggests that a
      hormone gradient may be involved. C-function expression does not appear to
      control the extent of female development, and indicates that genes which are
      downstream of the organ-identity genes must control organ suppression.

PMID- 15720683
TI  - Inhibition of RNA and protein synthesis in pollen tube development of Pinus
      bungeana by actinomycin D and cycloheximide.
AB  - * The effects of actinomycin D and cycloheximide on RNA and protein synthesis
      were investigated during pollen tube development of Pinus bungeana. * RNA and
      protein contents, protein expression patterns, cell wall components and
      ultrastructural changes of pollen tubes were studied using spectrophotometry, SDS
      PAGE electrophoresis, Fourier transformed infrared (FTIR) microspectroscopy and
      transmission electron microscopy (TEM). * Pollen grains germinated in the
      presence of actinomycin D, but tube elongation and RNA synthesis were inhibited.
      By contrast, cycloheximide inhibited pollen germination and protein synthesis,
      induced abnormal tube morphology, and retarded the tube growth rate. SDS-PAGE
      analysis showed that protein expression patterns changed distinctly, with some
      proteins being specific for each phase. FTIR microspectroscopy established
      significant changes in the chemical composition of pollen tube walls. TEM
      analysis revealed the inhibitors caused disintegration of organelles involved in
      the secretory system. * These results suggested RNA necessary for pollen
      germination and early tube growth were present already in the pollen grains
      before germination, while the initiation of germination and the maintenance of
      pollen tube elongation depended on continuous protein synthesis.

PMID- 15720684
TI  - Development and organization of the central vacuole of Acetabularia acetabulum.
AB  - * Here we analyzed the shape of the central vacuole of Acetabularia acetabulum by
      visualizing its development during diplophase (from juvenility through
      reproduction) and haplophase (from meiosis through mating). * Light microscopy
      and whole-organism applications of a pH-sensitive dye, neutral red, were used to
      visualize the anatomy of the central vacuole. We studied connectivity within the
      thallus by locally applying dye to morphologically distinct regions (rhizoid,
      stalk, apex, hairs) and observing dye movements. * In vegetative thalli most of
      the rhizoid, stalk and young hairs stained with dye. In reproductive structures
      (caps, gametangia) dye also stained the majority of the interiors. When applied
      to small areas, dye moved at different rates through each region of the thallus
      (e.g. within the stalk). Dye moved from younger hairs, but not from older hairs,
      into the stalk. Errors in incorporation of central vacuole into gametangia
      occurred at <10(-5). * These data indicate that the central vacuole of A.
      acetabulum is a ramified polar organelle with, potentially, a gel-like sap that
      actively remodels its morphology during development.

PMID- 15720685
TI  - Caesium-affected gene expression in Arabidopsis thaliana.
AB  - * Excessive caesium can be toxic to plants. Here we investigated Cs uptake and
      caesium-induced gene expression in Arabidopsis thaliana. * Accumulation was
      measured in plants grown for 5 wk on agar supplemented with nontoxic and up to
      toxic levels of Cs. Caesium-induced gene expression was studied by suppression
      subtractive hybridization (SSH) and RT-PCR. * Caesium accumulated in leaf
      rosettes dependent upon the external concentration in the growth media, whereas
      the potassium concentration decreased in rosettes. At a concentration of 850
      microM, Cs plants showed reduced development, and withered with an increase in
      concentration to 1 mM Cs. SSH resulted in the isolation of 73 clones that were
      differentially expressed at a Cs concentration of 150 microM. Most of the genes
      identified belong to groups of genes encoding proteins in stress defence,
      detoxification, transport, homeostasis and general metabolism, and proteins
      controlling transcription and translation. * The present study identified a
      number of marker genes for Cs in Arabidopsis grown under nontoxic Cs
      concentrations, indicating that Cs acts as an abiotic stress factor.

PMID- 15720686
TI  - Comparison of root absorption, translocation and tolerance of arsenic in the
      hyperaccumulator Pteris vittata and the nonhyperaccumulator Pteris tremula.
AB  - * Several fern species can hyperaccumulate arsenic, although the mechanisms are
      not fully understood. Here we investigate the roles of root absorption,
      translocation and tolerance in As hyperaccumulation by comparing the
      hyperaccumulator Pteris vittata and the nonhyperaccumulator Pteris tremula. * The
      two species were grown in a pot experiment with 0-500 mg As kg-1 added as
      arsenate, and in a short-term (8 h) uptake experiment with 5 microM arsenate
      under phosphorus-sufficient conditions. * In the pot experiment, P. vittata
      accumulated up to 2500 mg As kg-1 frond d. wt and suffered no phytotoxicity. P.
      tremula accumulated<100 mg As kg-1 frond d. wt and suffered severe phytotoxicity
      with additions of >or=25 mg As kg-1. In the short-term uptake experiment, P.
      vittata had a 2.2-fold higher rate of arsenate uptake than P. tremula, and
      distributed more As taken up to the fronds (76%) than did P. tremula (9%). * Our
      results show that enhanced root uptake, efficient root-to-shoot translocation,
      and a much elevated tolerance through internal detoxification all contribute to
      As hyperaccumulation in P. vittata.

PMID- 15720687
TI  - Palatability of Thlaspi caerulescens for snails: influence of zinc and
      glucosinolates.
AB  - * The hypothesis that zinc (Zn) hyperaccumulation defends Thlaspi caerulescens
      against herbivores is tested with the snail Helix aspersa. We investigated the
      effects of leaf zinc, cadmium, glucosinolate, nitrogen and dry matter
      concentrations on the feeding preferences of snails. * Four T. caerulescens
      populations from southern France (two from metalliferous and two from normal
      soils) were grown on low- and high-Zn soils to obtain contrasting leaf Zn
      concentrations. Plants were also collected in the field, and binary feeding
      choices involving low- and high-Zn leaves were conducted. * Foliar Zn, Cd, N and
      dry matter concentrations did not affect the feeding choices of snails, whereas
      glucosinolate had a significant negative effect on herbivore preferences.
      Compared with metallicolous plants, nonmetallicolous ones appeared to be better
      protected against snails, whatever their Zn concentration. * These results do not
      support the defence hypothesis, as glucosinolates appear to decrease the degree
      of herbivory when Zn does not.

PMID- 15720688
TI  - The beneficial effect of aluminium and the role of citrate in Al accumulation in
      Melastoma malabathricum.
AB  - * Here we investigated the beneficial effect of aluminium (Al) on the development
      of the Al accumulating plant Melastoma malabathricum. * Seedlings of M.
      malabathricum were cultivated in a nutrient solution containing 0.5 mM Al and
      compared with barley (Hordeum vulgare). In addition, roots of M. malabathricum
      were divided into one part growing in a nutrient solution, and the other part
      growing in a calcium solution. Al (0.5 mM) was applied to either solution. * Al
      induced improvements of the root activity contributed to a growth enhancement in
      M. malabathricum. Al exposure without nutrients did not increase root growth and
      Al accumulation in the leaves. The beneficial effect, however, was induced by the
      combination of Al and nutrients. * We suggest that without nutrients roots are
      not able to synthesize an adequate amount of citrate that is required for
      transporting Al to the leaves. High Al levels in the plant tissues and/or an
      interaction of Al with particular nutrient elements in the apoplast of root cells
      appear to be essential to exert the beneficial effect of Al.

PMID- 15720689
TI  - Internal iron biomineralization in Imperata cylindrica, a perennial grass:
      chemical composition, speciation and plant localization.
AB  - * The analysis of metal distribution in Imperata cylindrica, a perennial grass
      isolated from the banks of Tinto River (Iberian Pyritic Belt), an extreme acidic
      environment with high content in metals, has shown a remarkable accumulation of
      iron. This property has been used to study iron speciation and its distribution
      among different tissues and structures of the plant. * Mossbauer (MS) and X-ray
      diffraction (XRD) were used to determine the iron species, scanning electron
      microscopy (SEM) to locate iron biominerals among plant tissue structures, and
      energy-dispersive X-ray microanalysis (EDAX), X-ray fluorescence (TXRF) and
      inductively coupled plasma emission spectroscopy (ICP-MS) to confirm their
      elemental composition. * The MS spectral analysis indicated that iron accumulated
      in this plant mainly as jarosite and ferritin. The presence of jarosite was
      confirmed by XRD and the distribution of both minerals in structures of different
      tissues was ascertained by SEM-EDAX analysis. * The convergent results obtained
      by complementary techniques suggest a complex iron management system in I.
      cylindrica, probably as a consequence of the environmental conditions of its
      habitat.

PMID- 15720690
TI  - Soil factors controlling mineral N uptake by Picea engelmannii seedlings: the
      importance of gross NH4+ production rates.
AB  - * Hydroponic studies suggest that plant nitrogen (N) demand determines the rate
      of mineral N uptake; however, field observations show N limitation to be
      widespread. Field experiments are needed to understand soil factors controlling
      mineral N uptake. * We planted Picea engelmannii seedlings that had initially
      been grown from sterilized seeds, on a recently clearcut site. We applied a
      hybrid isotope dilution/pulse labelling technique to compare the gross production
      rate, concomitantly to the plant uptake rate, of soil mineral N. We also measured
      mineral N concentrations, microbial N, and percent ectomycorrhizal root tips. *
      Gross NH4+ production rate was the most important determinant of plant uptake
      rate. Exploratory path analysis suggested that plant uptake was also determined
      by microbial N, which was, in turn, determined by soil mineral N concentrations.
      Percent ectomycorrhizal root tips was negatively related to gross NO3- production
      rate and microbial N concentrations. * We conclude that nutrient flux density is
      important in controlling plant uptake. Mycorrhizal colonization may alter N
      dynamics in the rhizosphere without affecting mineral N uptake by seedlings.

PMID- 15720691
TI  - Molecular tagging of a senescence gene by introgression mapping of a stay-green
      mutation from Festuca pratensis.
AB  - * Intergeneric hybrids between Lolium multiflorum and Festuca pratensis (Lm/Fp)
      and their derivatives exhibit a unique combination of genetic and cytogenetic
      characteristics: chromosomes undergo a high frequency of homoeologous
      recombination at meiosis; the chromosomes of the two species can easily be
      discriminated by genomic in situ hybridization (GISH); recombination occurs along
      the entire length of homoeologous bivalents; a high frequency of marker
      polymorphism is observed between the two species. * This combination of
      characters has been used to transfer and isolate a F. pratensis chromosome
      segment carrying a mutant 'stay-green' gene conferring a disrupted leaf
      senescence phenotype into L. multiflorum. * The genetic location within the
      introgressed F. pratensis segment of the senescence gene has been mapped using
      amplified fragment length polymorphisms (AFLPs), and F. pratensis-specific AFLP
      markers closely flanking the green gene have been cloned. * The use of these
      cloned sequences as markers for the stay-green locus in marker-assisted selection
      programmes has been tested. The potential application of Lm/Fp introgressions as
      a tool for the map-based cloning of introgressed Fp genes is discussed.

PMID- 15720692
TI  - Local and systemic changes in arginine decarboxylase activity, putrescine levels
      and putrescine catabolism in wounded oilseed rape.
AB  - * Here we report the effect of mechanical wounding on putrescine biosynthesis and
      catabolism in oilseed rape (Brassica napus ssp. oleifera). * The lamina of first
      leaves was wounded by crushing with forceps, and first and second leaves were
      harvested at various intervals over a 24 h period. Levels of free polyamines were
      measured and activities of enzymes of polyamine biosynthesis and catabolism were
      assayed in the harvested tissue. * Mechanical wounding of the first leaves led to
      significant, but transient, increases in arginine decarboxylase (ADC) activity
      and levels of free putrescine in the wounded first leaf and in unwounded second
      leaves. The increased putrescine appeared to be the result of a combination of
      increased ADC activity, coupled with reduced putrescine catabolism, as activity
      of the oxidative enzyme diamine oxidase was significantly reduced following
      wounding, both locally and systemically. * The role of the increased free
      putrescine in the wound response of oilseed rape is not known, although the
      possibility that it is used to form putrescine conjugates is worthy of further
      investigation.

PMID- 15720693
TI  - Molecular characterization and expression of a cDNA encoding fructan:fructan 6G
      fructosyltransferase from asparagus (Asparagus officinalis).
AB  - * Fructan:fructan 6G-fructosyltransferase (6G-FFT) catalyses a
      transfructosylation from fructooligosaccharides to C6 of the glucose residue of
      sucrose or fructooligosacchrides. In asparagus (Asparagus officinalis), 6G-FFT is
      important for the synthesis of inulin neoseries fructan. Here, we report the
      isolation and functional analysis of the gene encoding asparagus 6G-FFT. * A cDNA
      clone was isolated from asparagus cDNA library. Recombinant protein was produced
      by expression system of Pichia pastoris. To measure enzymatic activity,
      recombinant protein was incubated with sucrose, 1-kestose, 1-kestose and sucrose,
      or neokestose. The reaction products were detected by high performance anion
      exchange chromatography. * The deduced amino acid sequence of isolated cDNA was
      similar to that of fructosyltransferases and vacuolar type invertases from
      plants. Recombinant protein mainly produced inulin neoseries fructan, such as 1F,
      6G-di-beta-D-fructofuranosylsucrose and neokestose. * Recombinant protein
      demonstrates 6G-FFT activity, and slight fructan:fructan 1-fructosyltransferase
      (1-FFT) activity. The ratio of 6G-FFT activity to 1-FFT activity was calculated
      to be 13. The characteristics of the recombinant protein closely resemble those
      of the 6G-FFT from asparagus roots, except for a difference in accompanying 1-FFT
      activity.

PMID- 15720694
TI  - Development of combined imbibition and hydrothermal threshold models to simulate
      maize (Zea mays) and chickpea (Cicer arietinum) seed germination in variable
      environments.
AB  - * The ability of hydrothermal time (HTT) and virtual osmotic potential (VOP)
      models to describe the kinetics of maize (Zea mays) and chickpea (Cicer
      arietinum) seed germination under variable conditions of water potential was
      investigated with a view to gaining an improved understanding of the impact of on
      farm seed priming on seedling establishment through simulation. * Germination
      and/or imbibition time courses were recorded over a wide range of constant
      temperatures and water potentials and simple stepwise changes in water potential.
      * Both models adequately described germination under constant environmental
      conditions, but not conditions of water potential that varied. To test the
      hypothesis that this inaccuracy resulted from the use of ambient water potential,
      a parsimonious model of seed imbibition was developed to calibrate the HTT and
      VOP models (IHTT and IVOP) and drive them with estimates of seed water potential.
      * The IHTT and IVOP models described germination during stepwise changes in water
      potential more accurately than the conventional models, and should contribute to
      improved predictions of germination time in the field.

PMID- 15720695
TI  - Leaf hydraulic capacity in ferns, conifers and angiosperms: impacts on
      photosynthetic maxima.
AB  - * The hydraulic plumbing of vascular plant leaves varies considerably between
      major plant groups both in the spatial organization of veins, as well as their
      anatomical structure. * Five conifers, three ferns and 12 angiosperm trees were
      selected from tropical and temperate forests to investigate whether the profound
      differences in foliar morphology of these groups lead to correspondingly profound
      differences in leaf hydraulic efficiency. * We found that angiosperm leaves
      spanned a range of leaf hydraulic conductance from 3.9 to 36 mmol m2 s-1 MPa-1,
      whereas ferns (5.9-11.4 mmol m-2 s-1 MPa-1) and conifers (1.6-9.0 mmol m-2 s-1
      MPa-1) were uniformly less conductive to liquid water. Leaf hydraulic conductance
      (Kleaf) correlated strongly with stomatal conductance indicating an internal leaf
      level regulation of liquid and vapour conductances. Photosynthetic capacity also
      increased with Kleaf, however, it became saturated at values of Kleaf over 20
      mmol m-2 s-1 MPa-1. * The data suggest that vessels in the leaves of the
      angiosperms studied provide them with the flexibility to produce highly
      conductive leaves with correspondingly high photosynthetic capacities relative to
      tracheid-bearing species.

PMID- 15720696
TI  - Xylem transport and shoot accumulation of lumichrome, a newly recognized
      rhizobial signal, alters root respiration, stomatal conductance, leaf
      transpiration and photosynthetic rates in legumes and cereals.
AB  - * Root respiration, stomatal conductance, leaf transpiration and photosynthetic
      rates were measured in phytotron and field-grown plants following the application
      of 5 or 10 nM lumichrome, 10 nM ABA (abscisic acid) and 10 ml of 0.2 OD600
      infective rhizobial cells. * Providing soybean and cowpea roots with their
      respective homologous rhizobia and/or purified lumichrome increased the
      concentration of this molecule in xylem sap and leaf extracts. Relative to
      control, rhizobial inoculation and lumichrome application significantly increased
      root respiration in maize, decreased it in lupin, but had no effect on the other
      test species. * Applying either lumichrome (10 nM), infective rhizobial cells or
      ABA to roots of plants for 44 h in growth chambers altered leaf stomatal
      conductance and transpiration in cowpea, lupin, soybean, Bambara groundnut and
      maize, but not in pea or sorghum. Where stomatal conductance was increased by
      lumichrome application or rhizobial inoculation, it resulted in increased leaf
      transpiration relative to control plants. Treating roots of field plants of
      cowpea with this metabolite up to 63 d after planting showed decreased stomatal
      conductance, which affected CO2 intake and reduction by Rubisco. * The effect of
      rhizobial inoculation closely mirrored that of lumichrome application to roots,
      indicating that rhizobial effects on these physiological activities were most
      likely due to lumichrome released into the rhizosphere.

PMID- 15720697
TI  - Winter photosynthesis by saplings of evergreen broad-leaved trees in a deciduous
      temperate forest.
AB  - * Here we investigated photosynthetic traits of evergreen species under a
      deciduous canopy in a temperate forest and revealed the importance of CO2
      assimilation during winter for annual CO2 assimilation. * Saplings were shaded by
      the canopy trees from spring through to autumn, but were less shaded during the
      winter months. Photosynthetic rates at light saturation (Aarea) were lower during
      winter than during the growing season. Aarea was higher in Camellia, Ilex and
      Photinia than in Castanopsis, Cleyera and Quercus during the winter, but differed
      little during summer and autumn. * Estimated daily CO2 assimilation (Aday) was
      higher during the winter than during the growing season in Camellia, Ilex and
      Photinia but was higher than that during the growing season only at the beginning
      and end of winter in Castanopsis, Cleyera and Quercus. Aday was higher in
      Camellia, Ilex and Photinia than in Castanopsis, Cleyera and Quercus but differed
      little among them during the growing season. * These results reveal the
      importance of winter CO2 assimilation for the growth of Camellia, Ilex and
      Photinia. Furthermore, differences in annual CO2 assimilation among species are
      strongly modified by species-specific photosynthetic traits during the winter
      under deciduous canopy trees.

PMID- 15720698
TI  - Variability of Cenococcum colonization and its ecophysiological significance for
      young conifers at alpine-treeline.
AB  - * Plants establishing in environments that are marginal for growth could be
      particularly sensitive to mycorrhizal associations. We investigated
      ectomycorrhizal colonization and its significance for young conifers growing at,
      or above, their normal limits for growth, in the alpine-treeline ecotone. *
      Colonization of seedlings (<1 yr old) and juveniles (2- to 10-yr-old) of Picea
      engelmannii and Abies lasiocarpa by Cenococcum geophilum was determined in a
      field study, and effects of Cenococcum on Picea seedling ecophysiology were
      investigated in a glasshouse. * Colonization by Cenococcum was c. 20-fold greater
      for juveniles than seedlings, and approximately 4-fold greater adjacent compared
      with approximately 7 m away from trees. Juveniles of Picea were more colonized at
      timberline than Abies, and the opposite relationship was observed in forest.
      Colonization enhanced seedling water potential, but not phosphorus concentrations
      or photosynthesis. * These landscape and age-dependent variations in colonization
      correspond well with known variations in conifer physiology and establishment
      near timberline. Facilitation of seedling establishment by older trees at alpine
      treeline may include a below-ground, mycorrhizal component that complements
      previously reported effects of trees on the microclimate and ecophysiology of
      seedlings.

PMID- 15720699
TI  - The use of conventional and quantitative real-time PCR assays for Polymyxa
      graminis to examine host plant resistance, inoculum levels and intraspecific
      variation.
AB  - * A real-time PCR protocol based on 18S rDNA sequences was developed to provide a
      specific, sensitive and quantitative assay for the root-infecting virus vector
      Polymyxa graminis. * The assay was calibrated with zoospore suspensions and
      inoculated roots and then shown to work with naturally infected plant roots and
      infested soil. Both the temperate P. graminis ribotypes previously described are
      detected but are not distinguished. DNA from related plasmodiophorids and from a
      range of fungi and plants was not detected. * Different genotypes of Triticum
      were grown in a soil infested with P. graminis and Soil-borne cereal mosaic virus
      (SBCMV). The genotypes differed in susceptibility to P. graminis, the least
      susceptible being the Triticum monococcum accession K-58505. * Conventional PCR
      assays and sequencing of amplified rDNA fragments showed that P. graminis
      isolates infecting wheat were mostly, but not exclusively, of ribotype II.
      Ribotype II was clearly associated with SBCMV transmission and seems to occur
      preferentially on wheat whereas ribotype I is mostly associated with barley.

PMID- 15720700
TI  - The occurrence of dauciform roots amongst Western Australian reeds, rushes and
      sedges, and the impact of phosphorus supply on dauciform-root development in
      Schoenus unispiculatus (Cyperaceae).
AB  - * The incidence of species that develop specialised 'dauciform' lateral roots,
      which are hypothesised to be important for phosphorus (P) acquisition, is
      uncertain. We investigated their occurrence in Australian reed, rush and sedge
      species, grown at low P concentration in nutrient solution, and studied the
      response of Schoenus unispiculatus (Cyperaceae) to a range of P concentrations. *
      We assessed the fraction of root biomass invested in dauciform roots, their
      respiration and net P-uptake rate, and the P status of roots and leaves. *
      Dauciform-root development occurred only in particular genera of Cyperaceae when
      grown at low P supply. Increased P supply was associated with increased growth of
      S. unispiculatus and increased leaf [P]. Dauciform-root growth was reduced by
      increased P supply, and reduced P uptake co-occurred with the complete
      suppression of dauciform roots. * The P-induced suppression of dauciform roots in
      Cyperaceae is similar to that observed for proteoid roots in members of
      Proteaceae and Lupinus albus. The response of dauciform roots to altered P supply
      and their absence from root systems of some sedge species are discussed in terms
      of managed and natural systems.

PMID- 15720701
TI  - Phosphate uptake, transport and transfer by the arbuscular mycorrhizal fungus
      Glomus intraradices is stimulated by increased carbohydrate availability.
AB  - * The influence of carbohydrate availability to mycorrhizal roots on uptake,
      metabolism and translocation of phosphate (P) by the fungus was examined in
      axenic cultures of transformed carrot (Daucus carota) roots in symbiosis with
      Glomus intraradices. * 14C-labelled carbohydrates, 33P-phosphate and energy
      dispersive X-ray microanalysis were used to follow the uptake and transfer of C
      and P in the arbuscular mycorrhizal (AM) symbiosis. * The uptake of P by the
      extraradical mycelium (ERM) and its translocation to the mycorrhizal roots was
      stimulated and the metabolic and spatial distribution of P within the fungus were
      altered in response to increased carbohydrate availability. Sucrose supply
      resulted in a decrease of polyphosphates and an increased incorporation into
      phospholipids and other growth-related P pools and also caused elevated
      cytoplasmic P levels in the intraradical mycelium (IRM) within the root and
      higher cytoplasmic P levels in the root cortex. * These findings indicate that
      the uptake of P by the fungus and its transfer to the host is also stimulated by
      the transfer of carbon from plant to fungus across the mycorrhizal interface.

PMID- 15720702
TI  - Fine roots, arbuscular mycorrhizal hyphae and soil nutrients in four neotropical
      rain forests: patterns across large geographic distances.
AB  - * It is commonly hypothesized that stand-level fine root biomass increases as
      soil fertility decreases both within and among tropical forests, but few data
      exist to test this prediction across broad geographic scales. This study
      investigated the relationships among fine roots, arbuscular mycorrhizal (AM)
      fungi and soil nutrients in four lowland, neotropical rainforests. * Within each
      forest, samples were collected from plots that differed in fertility and above
      ground biomass, and fine roots, AM hyphae and total soil nutrients were measured.
      * Among sites, total fine root mass varied by a factor of three, from 237+/-19 g
      m-2 in Costa Rica to 800+/-116 g m-2 in Brazil (0-40 cm depth). Both root mass
      and length were negatively correlated to soil nitrogen and phosphorus, but AM
      hyphae were not related to nutrients, root properties or above-ground biomass. *
      These results suggest that understanding how soil fertility affects fine roots is
      an additional factor that may improve the representation of root functions in
      global biogeochemical models or biome-wide averages of root properties in
      tropical forests.

PMID- 15720703
TI  - Russulaceae and Thelephoraceae form ectomycorrhizas with members of the
      Nyctaginaceae (Caryophyllales) in the tropical mountain rain forest of southern
      Ecuador.
AB  - * Three members of the Nyctaginaceae, two Neea species and one Guapira species,
      occurred scattered within a very species-rich neotropical mountain rain forest.
      The three species were found to form ectomycorrhizas of very distinctive
      characters, while all other tree species examined formed arbuscular mycorrhizas.
      * The ectomycorrhizas were structurally typified according to light and
      transmission electron microscope investigations. The internal transcribed spacer
      (ITS) rDNA and part of the nuclear large subunit (LSU, 28S) rDNA of the
      mycorrhiza forming fungi were amplified and sequenced. Phylogenetic analyses were
      carried out. * Neea species 1 was found to form typical ectomycorrhizas with five
      different fungal species, Russula puiggarii, Lactarius sp., two Tomentella or
      Thelephora species, and one ascomycete. Neea species 2 and the Guapira species
      were associated with only one fungus each, a Tomentella/Thelephora species
      clustering closely together in an ITS-neighbour-joining tree. The long and fine
      rootlets of the Guapira species showed proximally a hyphal mantle and a Hartig
      net, but distally intracellular fungal colonization of the epidermis and root
      hair development. The ectomycorrhizal segments of the long roots of Neea species
      2 displayed a hyphal mantle and a Hartig net around alive root-hair-like
      outgrowths of the epidermal cells. * The distribution and the evolution of
      ectomycorrhizas in the predominantly neotropic Nyctaginaceae are discussed.

PMID- 15720704
TI  - Duplication and DNA segmental loss in the rice genome: implications for
      diploidization.
AB  - * Large-scale duplication events have been recently uncovered in the rice genome,
      but different interpretations were proposed regarding the extent of the
      duplications. * Through analysing the 370 Mb genome sequences assembled into 12
      chromosomes of Oryza sativa subspecies indica, we detected 10 duplicated blocks
      on all 12 chromosomes that contained 47% of the total predicted genes. Based on
      the phylogenetic analysis, we inferred that this was a result of a genome
      duplication that occurred c. 70 million years ago, supporting the polyploidy
      origin of the rice genome. In addition, a segmental duplication was also
      identified involving chromosomes 11 and 12, which occurred c. 5 million years
      ago. * Following the duplications, there have been large-scale chromosomal
      rearrangements and deletions. About 30-65% of duplicated genes were lost shortly
      after the duplications, leading to a rapid diploidization. * Together with other
      lines of evidence, we propose that polyploidization is still an ongoing process
      in grasses of polyploidy origins.

PMID- 15720705
TI  - A simple method for discriminating between cell membrane and cytosolic proteins.
AB  - * Transgenic plants expressing either green fluorescent protein (GFP)-genomic DNA
      or GFP-cDNA fusions have been used as powerful tools to define the subcellular
      localization of many proteins. Because most plant cells are highly vacuolated,
      the cytosol is confined to a thin layer at the periphery of the cells, making it
      very difficult to distinguish among cell wall, cell membrane and cytosolic GFP
      fusion proteins. * Plasmolysis tests inform about cell-wall localization of GFP
      tagged proteins, but they do not discriminate between its cell membrane and/or
      cytoplasmic localization. By observing the GFP signal in transgenic protoplasts
      placed at a hypotonic solution, it was possible to distinguish between cell
      membrane and cytosolic GFP-tagged proteins. * The osmotic disruption of the
      protoplast vacuole in the hypotonic solution allows the diffusion of the GFP
      signal from the cell periphery to the central part of the cell volume when the
      GFP is fused to a soluble protein. By contrast, such diffusion does not occur
      when the protein under study is attached to the cell membrane. * The present
      method is easier, faster and cheaper than subcellular fractionating studies
      and/or immunoelectron microscopy, which have been traditionally used to discern
      between cell membrane and cytosolic proteins.

PMID- 15720706
TI  - Mold sensitization is common amongst patients with severe asthma requiring
      multiple hospital admissions.
AB  - BACKGROUND: Multiple studies have linked fungal exposure to asthma, but the link
      to severe asthma is controversial. We studied the relationship between asthma
      severity and immediate type hypersensitivity to mold (fungal) and non-mold
      allergens in 181 asthmatic subjects. METHODS: We recruited asthma patients aged
      16 to 60 years at a University hospital and a nearby General Practice. Patients
      were categorized according to the lifetime number of hospital admissions for
      asthma (82 never admitted, 53 one admission, 46 multiple admissions). All
      subjects had allergy skin prick tests performed for 5 mold allergens
      (Aspergillus, Alternaria, Cladosporium, Penicillium and Candida) and 4 other
      common inhalant allergens (D. pteronyssinus, Grass Pollen, Cat and Dog). RESULTS:
      Skin reactivity to all allergens was commonest in the group with multiple
      admissions. This trend was strongest for mold allergens and dog allergen and
      weakest for D. pteronyssinus. 76% of patients with multiple admissions had at
      least one positive mold skin test compared with 16%-19% of other asthma patients;
      (Chi squared p < 0.0001). Multiple mold reactions were also much commoner in the
      group with multiple admissions (50% V 5% and 6%; p < 0.0001). The number of
      asthma admissions was related to the number and size of positive mold skin
      allergy tests (Spearman Correlation Coefficient r = 0.60, p < 0.0001) and less
      strongly correlated to the number and size of non-mold allergy tests (r = 0.34, p
      = 0.0005). Hospital admissions for asthma patients aged 16-40 were commonest
      during the mold spore season (July to October) whereas admissions of patients
      aged above 40 peaked in November-February (Chi Squared, p < 0.02). CONCLUSION:
      These findings support previous suggestions that mold sensitization may be
      associated with severe asthma attacks requiring hospital admission.

PMID- 15720707
TI  - Nonrandom distribution and frequencies of genomic and EST-derived microsatellite
      markers in rice, wheat, and barley.
AB  - BACKGROUND: Earlier comparative maps between the genomes of rice (Oryza sativa
      L.), barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.) were linkage
      maps based on cDNA-RFLP markers. The low number of polymorphic RFLP markers has
      limited the development of dense genetic maps in wheat and the number of
      available anchor points in comparative maps. Higher density comparative maps
      using PCR-based anchor markers are necessary to better estimate the conservation
      of colinearity among cereal genomes. The purposes of this study were to
      characterize the proportion of transcribed DNA sequences containing simple
      sequence repeats (SSR or microsatellites) by length and motif for wheat, barley
      and rice and to determine in-silico rice genome locations for primer sets
      developed for wheat and barley Expressed Sequence Tags. RESULTS: The proportions
      of SSR types (di-, tri-, tetra-, and penta-nucleotide repeats) and motifs varied
      with the length of the SSRs within and among the three species, with
      trinucleotide SSRs being the most frequent. Distributions of genomic
      microsatellites (gSSRs), EST-derived microsatellites (EST-SSRs), and transcribed
      regions in the contiguous sequence of rice chromosome 1 were highly correlated.
      More than 13,000 primer pairs were developed for use by the cereal research
      community as potential markers in wheat, barley and rice. CONCLUSION:
      Trinucleotide SSRs were the most common type in each of the species; however, the
      relative proportions of SSR types and motifs differed among rice, wheat, and
      barley. Genomic microsatellites were found to be primarily located in gene-rich
      regions of the rice genome. Microsatellite markers derived from the use of non
      redundant EST-SSRs are an economic and efficient alternative to RFLP for
      comparative mapping in cereals.

PMID- 15720708
TI  - Selection of reference genes for gene expression studies in human neutrophils by
      real-time PCR.
AB  - BACKGROUND: Reference genes, which are often referred to housekeeping genes, are
      frequently used to normalize mRNA levels between different samples. However the
      expression level of these genes may vary among tissues or cells, and may change
      under certain circumstances. Thus the selection of reference gene(s) is critical
      for gene expression studies. For this purpose, 10 commonly used housekeeping
      genes were investigated in isolated human neutrophils. RESULTS: Initial screening
      of the expression pattern demonstrated that 3 of the 10 genes were expressed at
      very low levels in neutrophils and were excluded from further analysis. The range
      of expression stability of the other 7 genes was (from most stable to least
      stable): GNB2L1 (Guanine nucleotide binding protein, beta polypeptide 2-like 1),
      HPRT1 (Hypoxanthine phosphoribosyl transferase 1), RPL32 (ribosomal protein L32),
      ACTB (beta-actin), B2M (beta-2-microglobulin), GAPD (glyceraldehyde-3-phosphate
      dehydrogenase) and TBP (TATA-binding protein). Relative expression levels of the
      genes (from high to low) were: B2M, ACTB, GAPD, RPL32, GNB2L1, TBP, and HPRT1.
      CONCLUSION: Our data suggest that GNB2L1, HPRT1, RPL32, ACTB, and B2M may be
      suitable reference genes in gene expression studies of neutrophils.

PMID- 15720709
TI  - Is there value in using physician billing claims along with other administrative
      health care data to document the burden of adolescent injury? An exploratory
      investigation with comparison to self-reports in Ontario, Canada.
AB  - BACKGROUND: Administrative health care databases may be particularly useful for
      injury surveillance, given that they are population-based, readily available, and
      relatively complete. Surveillance based on administrative data, though, is often
      restricted to injuries that result in hospitalization. Adding physician billing
      data to administrative data-based surveillance efforts may improve
      comprehensiveness, but the feasibility of such an approach has rarely been
      examined. It is also not clear how injury surveillance information obtained using
      administrative health care databases compares with that obtained using self
      report surveys. This study explored the value of using physician billing data
      along with hospitalization data for the surveillance of adolescent injuries in
      Ontario, Canada. We aimed i) to document the burden of adolescent injury using
      administrative health care data, focusing on the relative contribution of
      physician billing information; and ii) to explore data quality issues by directly
      comparing adolescent injuries identified in administrative and self-report data.
      METHODS: The sample included adolescents aged 12 to 19 years who participated in
      the 1996-1997 cross-sectional Ontario Health Survey, and whose survey responses
      were linked to administrative health care datasets (N = 2067). Descriptive
      analysis was used to document the burden of injuries as a proportion of all
      physician care by gender and location of care, and to examine the distribution of
      both administratively-defined and self-reported activity-limiting injuries
      according to demographic characteristics. Administratively-defined and self
      reported injuries were also directly compared at the individual level. RESULTS:
      Approximately 10% of physician care for the sample was identified as injury
      related. While 18.8% of adolescents had self-reported injury in the previous
      year, 25.0% had documented administratively-defined injury. The distribution of
      injuries according to demographic characteristics was similar across data
      sources, but congruence was low at the individual level. Possible reasons for
      discrepancies between the data sources included recall errors in the survey data
      and errors in the physician billing data algorithm. CONCLUSION: If further
      validated, physician billing data could be used along with hospital inpatient
      data to make an important and unique contribution to adolescent injury
      surveillance. The limitations inherent in different datasets highlight the need
      to continue rely on multiple information sources for complete injury surveillance
      information.

PMID- 15720710
TI  - Central neuropeptide Y receptors are involved in 3rd ventricular ghrelin induced
      alteration of colonic transit time in conscious fed rats.
AB  - BACKGROUND: Feeding related peptides have been shown to be additionally involved
      in the central autonomic control of gastrointestinal functions. Recent studies
      have shown that ghrelin, a stomach-derived orexigenic peptide, is involved in the
      autonomic regulation of GI function besides feeding behavior. Pharmacological
      evidence indicates that ghrelin effects on food intake are mediated by
      neuropeptide Y in the central nervous system. METHODS: In the present study we
      examine the role of ghrelin in the central autonomic control of GI motility using
      intracerobroventricular and IP microinjections in a freely moving conscious rat
      model. Further the hypothesis that a functional relationship between NPY and
      ghrelin within the CNS exists was addressed. RESULTS: ICV injections of ghrelin
      (0.03 nmol, 0.3 nmol and 3.0 nmol/5 microl and saline controls) decreased the
      colonic transit time up to 43%. IP injections of ghrelin (0.3 nmol - 3.0 nmol kg(
      1) BW and saline controls) decreased colonic transit time dose related. Central
      administration of the NPY1 receptor antagonist, BIBP-3226, prior to centrally or
      peripherally administration of ghrelin antagonized the ghrelin induced
      stimulation of colonic transit. On the contrary ICV-pretreatment with the NPY2
      receptor antagonist, BIIE-0246, failed to modulate the ghrelin induced
      stimulation of colonic motility. CONCLUSION: The results suggest that ghrelin
      acts in the central nervous system to modulate gastrointestinal motor function
      utilizing NPY1 receptor dependent mechanisms.

PMID- 15720712
TI  - Dispersion of cardiac action potential duration and the initiation of re-entry: a
      computational study.
AB  - BACKGROUND: The initiation of re-entrant cardiac arrhythmias is associated with
      increased dispersion of repolarisation, but the details are difficult to
      investigate either experimentally or clinically. We used a computational model of
      cardiac tissue to study systematically the association between action potential
      duration (APD) dispersion and susceptibility to re-entry. METHODS: We simulated a
      60 x 60 mm2 D sheet of cardiac ventricular tissue using the Luo-Rudy phase 1
      model, with maximal conductance of the K+ channel gKmax set to 0.004 mS mm(-2).
      Within the central 40 x 40 mm region we introduced square regions with prolonged
      APD by reducing gKmax to between 0.001 and 0.003 mS mm(-2). We varied (i) the
      spatial scale of these regions, (ii) the magnitude of gKmax in these regions, and
      (iii) cell-to-cell coupling. RESULTS: Changing spatial scale from 5 to 20 mm
      increased APD dispersion from 49 to 102 ms, and the susceptible window from 31 to
      86 ms. Decreasing gKmax in regions with prolonged APD from 0.003 to 0.001 mS mm-2
      increased APD dispersion from 22 to 70 ms, and the susceptible window from <1 to
      56 ms. Decreasing cell-to-cell coupling by changing the diffusion coefficient
      from 0.2 to 0.05 mm2 ms(-1) increased APD dispersion from 57 to 88 ms, and
      increased the susceptible window from 41 to 74 ms. CONCLUSION: We found a close
      association between increased APD dispersion and susceptibility to re-entrant
      arrhythmias, when APD dispersion is increased by larger spatial scale of
      heterogeneity, greater electrophysiological heterogeneity, and weaker cell-to
      cell coupling.

PMID- 15720711
TI  - Identification of a new family of putative PD-(D/E)XK nucleases with unusual
      phylogenomic distribution and a new type of the active site.
AB  - BACKGROUND: Prediction of structure and function for uncharacterized protein
      families by identification of evolutionary links to characterized families and
      known structures is one of the cornerstones of genomics. Theoretical assignment
      of three-dimensional folds and prediction of protein function even at a very
      general level can facilitate the experimental determination of the molecular
      mechanism of action and the role that members of a given protein family fulfill
      in the cell. Here, we predict the three-dimensional fold and study the
      phylogenomic distribution of members of a large family of uncharacterized
      proteins classified in the Clusters of Orthologous Groups database as COG4636.
      RESULTS: Using protein fold-recognition we found that members of COG4636 are
      remotely related to Holliday junction resolvases and other nucleases from the PD
      (D/E)XK superfamily. Structure modeling and sequence analyses suggest that most
      members of COG4636 exhibit a new, unusual variant of the putative active site, in
      which the catalytic Lys residue migrated in the sequence, but retained similar
      spatial position with respect to other functionally important residues. Sequence
      analyses revealed that members of COG4636 and their homologs are found mainly in
      Cyanobacteria, but also in other bacterial phyla. They undergo horizontal
      transfer and extensive proliferation in the colonized genomes; for instance in
      Gloeobacter violaceus PCC 7421 they comprise over 2% of all protein-encoding
      genes. Thus, members of COG4636 appear to be a new type of selfish genetic
      elements, which may fulfill an important role in the genome dynamics of
      Cyanobacteria and other species they invaded. Our analyses provide a platform for
      experimental determination of the molecular and cellular function of members of
      this large protein family. CONCLUSION: After submission of this manuscript, a
      crystal structure of one of the COG4636 members was released in the Protein Data
      Bank (code 1wdj; Idaka, M., Wada, T., Murayama, K., Terada, T., Kuramitsu, S.,
      Shirouzu, M., Yokoyama, S.: Crystal structure of Tt1808 from Thermus thermophilus
      Hb8, to be published). Our analysis of the Tt1808 structure reveals that we
      correctly predicted all functionally important features of the COG4636 family,
      including the membership in the PD-(D/E)xK superfamily of nucleases, the three
      dimensional fold, the putative catalytic residues, and the unusual configuration
      of the active site.

PMID- 15720713
TI  - Malaria and urbanization in sub-Saharan Africa.
AB  - There are already 40 cities in Africa with over 1 million inhabitants and the
      United Nations Environmental Programme estimates that by 2025 over 800 million
      people will live in urban areas. Recognizing that malaria control can improve the
      health of the vulnerable and remove a major obstacle to their economic
      development, the Malaria Knowledge Programme of the Liverpool School of Tropical
      Medicine and the Systemwide Initiative on Malaria and Agriculture convened a
      multi-sectoral technical consultation on urban malaria in Pretoria, South Africa
      from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies
      for the assessment and control of urban malaria. This commentary reflects the
      discussions held during the meeting and aims to inform researchers and policy
      makers of the potential for containing and reversing the emerging problem of
      urban malaria.

PMID- 15720715
TI  - Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing
      tumour mRNA as potential cancer vaccines against leukemia.
AB  - BACKGROUND: Leukemia is a clonal disorder characterized by uncontrolled
      proliferation of haematopoietic cells, and represents the most common form of
      cancer in children. Advances in therapy for childhood leukemia have relied
      increasingly on the use of high-dose chemotherapy often combined with stem-cell
      transplantation. Despite a high success rate and intensification of therapy,
      children still suffer from relapse and progressive disease resistant to further
      therapy. Thus, novel forms of therapy are required. METHODS: This study focuses
      on dendritic cell (DC) vaccination of childhood leukemia and evaluates the in
      vitro efficacy of different strategies for antigen loading of professional
      antigen-presenting cells. We have compared DCs either loaded with apoptotic
      leukemia cells or transfected with mRNA from the same leukemia cell line, Jurkat
      E6, for their capacity to induce specific CD4+ and CD8+ T-cell responses.
      Monocyte-derived DCs from healthy donors were loaded with tumor antigen, matured
      and co-cultured with autologous T cells. After one week, T-cell responses against
      antigen-loaded DCs were measured by enzyme-linked immunosorbent spot (ELISPOT)
      assay. RESULTS: DCs loaded with apoptotic Jurkat E6 cells or transfected with
      Jurkat E6-cell mRNA were both able to elicit specific T-cell responses in vitro.
      IFNgamma-secreting T cells were observed in both the CD4+ and CD8+ subsets.
      CONCLUSION: The results indicate that loading of DCs with apoptotic leukemia
      cells or transfection with tumour mRNA represent promising strategies for
      development of cancer vaccines for treatment of childhood leukemia.

PMID- 15720714
TI  - Construction and analysis of tag single nucleotide polymorphism maps for six
      human-mouse orthologous candidate genes in type 1 diabetes.
AB  - BACKGROUND: One strategy to help identify susceptibility genes for complex,
      multifactorial diseases is to map disease loci in a representative animal model
      of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1
      diabetes. Linkage and congenic strain analyses have identified several NOD mouse
      Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome
      intervals, for which the orthologous regions in the human genome can be
      identified. Here, we have conducted re-sequencing and association analysis of six
      orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to
      Nramp1/Slc11a1 in Idd5.2), FRAP1 (orthologous to Frap1 in Idd9.2), 4
      1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3), CD101/IGSF2
      (orthologous to Cd101/Igsf2 in Idd10), B2M (orthologous to B2m in Idd13) and VAV3
      (orthologous to Vav3 in Idd18). RESULTS: Re-sequencing of a total of 110 kb of
      DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide
      polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a
      microsatellite were selected and genotyped in up to 1,632 type 1 diabetes
      families and 1,709 cases and 1,829 controls. CONCLUSION: None of the candidate
      regions showed evidence of association with type 1 diabetes (P values > 0.2),
      indicating that common variation in these key candidate genes does not play a
      major role in type 1 diabetes susceptibility in the European ancestry populations
      studied.

PMID- 15720717
TI  - Using purine skews to predict genes in AT-rich poxviruses.
AB  - BACKGROUND: Clusters or runs of purines on the mRNA synonymous strand have been
      found in many different organisms including orthopoxviruses. The purine bias that
      is exhibited by these clusters can be observed using a purine skew and in the
      case of poxviruses, these skews can be used to help determine the coding strand
      of a particular segment of the genome. Combined with previous findings that minor
      ORFs have lower than average aspartate and glutamate composition and higher than
      average serine composition, purine content can be used to predict the likelihood
      of a poxvirus ORF being a "real gene". RESULTS: Using purine skews and a
      "quality" measure designed to incorporate previous findings about minor ORFs, we
      have found that in our training case (vaccinia virus strain Copenhagen), 59 of 65
      minor (small and unlikely to be a real genes) ORFs were correctly classified as
      being minor. Of the 201 major (large and likely to be real genes) vaccinia ORFs,
      192 were correctly classified as being major. Performing a similar analysis with
      the entomopoxvirus amsacta moorei (AMEV), it was found that 4 major ORFs were
      incorrectly classified as minor and 9 minor ORFs were incorrectly classified as
      major. The purine abundance observed for major ORFs in vaccinia virus was found
      to stem primarily from the first codon position with both the second and third
      codon positions containing roughly equal amounts of purines and pyrimidines.
      CONCLUSION: Purine skews and a "quality" measure can be used to predict
      functional ORFs and purine skews in particular can be used to determine which of
      two overlapping ORFs is most likely to be the real gene if neither of the two
      ORFs has orthologs in other poxviruses.

PMID- 15720716
TI  - Low adherence with antihypertensives in actual practice: the association with
      social participation--a multilevel analysis.
AB  - BACKGROUND: Low adherence is a key factor in explaining impaired effectiveness
      and efficiency in the pharmacological treatment of hypertension. However, little
      is known about which factors determine low adherence in actual practice. The
      purpose of this study is to examine whether low social participation is
      associated with low adherence with antihypertensive medication, and if this
      association is modified by the municipality of residence. METHODS: 1288 users of
      antihypertensive medication were identified from The Health Survey in Scania
      2000, Sweden. The outcome was low adherence with antihypertensives during the
      last two weeks. Multilevel logistic regression with participants at the first
      level and municipalities at the second level was used for analyses of the data.
      RESULTS: Low social participation was associated with low adherence with
      antihypertensives during the last two weeks (OR = 2.05, 95% CI: 1.05-3.99),
      independently of low educational level. However, after additional adjustment for
      poor self-rated health and poor psychological health, the association between low
      social participation and low adherence with antihypertensives during the last two
      weeks remained but was not conclusive (OR = 1.80, 95% CI: 0.90-3.61).
      Furthermore, the association between low social participation and low adherence
      with antihypertensives during the last two weeks varied among municipalities in
      Scania (i.e., cross-level interaction). CONCLUSION: Low social participation
      seems to be associated with low adherence with antihypertensives during the last
      two weeks, and this association may be modified by the municipality of residence.
      Future studies aimed at investigating health-related behaviours in general and
      low adherence with medication in particular might benefit if they consider area
      of residence.

PMID- 15720718
TI  - A novel replication-independent histone H2a gene in mouse.
AB  - BACKGROUND: An uncharacterized histone H2a-coding transcript (E130307C13) has
      been cloned from a mouse full-length cDNA library. This transcript is encoded on
      chromosome 6, approximately 4 kb upstream of a histone H4 gene, Hist4h4. The
      proteins encoded by this transcript and the human H2afj mRNA isoform-2 have the
      highest amino acid similarity. In this paper, we characterize it from the
      expression pattern given by quantitative RT-PCR. RESULTS: Quantitative RT-PCR
      indicated that the gene that encodes E130307C13 (E130307C13) is regulated in a
      replication-independent manner, and therefore it is H2afj. Certainly, H2afj
      transcript lacks a stem-loop structure at the 3'-UTR but contains a poly (A)
      signal. In addition, its promoter region has a different structure from those of
      the replication-dependent histone H2a genes. CONCLUSION: The bioinformatics imply
      that E130307C13 is a replication-independent H2a gene. In addition, quantitative
      RT-PCR analysis shows that it is replication-independent. Thus, it is H2afj, a
      novel replication-independent H2a gene in mouse.

PMID- 15720719
TI  - PSSM-based prediction of DNA binding sites in proteins.
AB  - BACKGROUND: Detection of DNA-binding sites in proteins is of enormous interest
      for technologies targeting gene regulation and manipulation. We have previously
      shown that a residue and its sequence neighbor information can be used to predict
      DNA-binding candidates in a protein sequence. This sequence-based prediction
      method is applicable even if no sequence homology with a previously known DNA
      binding protein is observed. Here we implement a neural network based algorithm
      to utilize evolutionary information of amino acid sequences in terms of their
      position specific scoring matrices (PSSMs) for a better prediction of DNA-binding
      sites. RESULTS: An average of sensitivity and specificity using PSSMs is up to
      8.7% better than the prediction with sequence information only. Much smaller data
      sets could be used to generate PSSM with minimal loss of prediction accuracy.
      CONCLUSION: One problem in using PSSM-derived prediction is obtaining lengthy and
      time-consuming alignments against large sequence databases. In order to speed up
      the process of generating PSSMs, we tried to use different reference data sets
      (sequence space) against which a target protein is scanned for PSI-BLAST
      iterations. We find that a very small set of proteins can actually be used as
      such a reference data without losing much of the prediction value. This makes the
      process of generating PSSMs very rapid and even amenable to be used at a genome
      level. A web server has been developed to provide these predictions of DNA
      binding sites for any new protein from its amino acid sequence. AVAILABILITY:
      Online predictions based on this method are available at
      http://www.netasa.org/dbs-pssm/

PMID- 15720720
TI  - Customized birth weight for gestational age standards: Perinatal mortality
      patterns are consistent with separate standards for males and females but not for
      blacks and whites.
AB  - BACKGROUND: Some currently available birth weight for gestational age standards
      are customized but others are not. We carried out a study to provide empirical
      justification for customizing such standards by sex and for whites and blacks in
      the United States. METHODS: We studied all male and female singleton live births
      and stillbirths (22 or more weeks of gestation; 500 g birth weight or over) in
      the United States in 1997 and 1998. White and black singleton live births and
      stillbirths were also examined. Qualitative congruence between gestational age
      specific growth restriction and perinatal mortality rates was used as the
      criterion for identifying the preferred standard. RESULTS: The fetuses at risk
      approach showed that males had higher perinatal mortality rates at all
      gestational ages compared with females. Gestational age-specific growth
      restriction rates based on a sex-specific standard were qualitatively consistent
      with gestational age-specific perinatal mortality rates among males and females.
      However, growth restriction patterns among males and females based on a unisex
      standard could not be reconciled with perinatal mortality patterns. Use of a
      single standard for whites and blacks resulted in gestational age-specific growth
      restriction rates that were qualitatively congruent with patterns of perinatal
      mortality, while use of separate race-specific standards led to growth
      restriction patterns that were incompatible with patterns of perinatal mortality.
      CONCLUSION: Qualitative congruence between growth restriction and perinatal
      mortality patterns provides an outcome-based justification for sex-specific birth
      weight for gestational age standards but not for the available race-specific
      standards for blacks and whites in the United States.

PMID- 15720721
TI  - Haematuria as a presentation of metastatic oesophageal carcinoma.
AB  - Haematuria is a classical symptom of urological disease often signifying a
      primary bladder cancer. Rarely, however, the presence of blood in the urine can
      be due to secondary spread of tumours into the bladder from distant sites.
      Notably this has been reported to occur in breast cancer, malignant melanoma and
      gastric cancers. Haematuria due to spread from a primary oesophageal cancer to
      the bladder has never been reported. We present a case of haematuria confirmed
      histologically to be due to metastases from a primary oesophageal tumour.
      Oesophageal cancer is capable of spread to all three neighbouring compartments
      (abdomen, chest and neck) and therefore has the potential to spread to unusual
      sites. Clinicians should always carefully regard haematuria in a patient
      previously treated for cancer and retain a high index of suspicion for distant
      metastases as being the cause.

PMID- 15720722
TI  - Dishevelled nuclear shuttling.
AB  - Structure-function analysis of the Dishevelled (Dsh) protein in frog embryos has
      defined sequences that regulate Dsh nuclear localization, which proves critical
      for Wnt signaling.

PMID- 15720723
TI  - Dishevelled and Wnt signaling: is the nucleus the final frontier?
AB  - The phosphoprotein Dishevelled (Dsh) is an essential component of Wnt signaling
      pathways and transduces signals into three separate branches, the canonical, non
      canonical and Ca2+ pathways. How Dsh focuses signaling into these branches
      remains mysterious, but a new study reveals the importance of nuclear
      localization of Dsh for pathway-specific activation.

PMID- 15720724
TI  - Nuclear localization is required for Dishevelled function in Wnt/beta-catenin
      signaling.
AB  - BACKGROUND: Dishevelled (Dsh) is a key component of multiple signaling pathways
      that are initiated by Wnt secreted ligands and Frizzled receptors during
      embryonic development. Although Dsh has been detected in a number of cellular
      compartments, the importance of its subcellular distribution for signaling
      remains to be determined. RESULTS: We report that Dsh protein accumulates in cell
      nuclei when Xenopus embryonic explants or mammalian cells are incubated with
      inhibitors of nuclear export or when a specific nuclear-export signal (NES) in
      Dsh is disrupted by mutagenesis. Dsh protein with a mutated NES, while
      predominantly nuclear, remains fully active in its ability to stimulate canonical
      Wnt signaling. Conversely, point mutations in conserved amino-acid residues that
      are essential for the nuclear localization of Dsh impair the ability of Dsh to
      activate downstream targets of Wnt signaling. When these conserved residues of
      Dsh are replaced with an unrelated SV40 nuclear localization signal, full Dsh
      activity is restored. Consistent with a signaling function for Dsh in the
      nucleus, treatment of cultured mammalian cells with medium containing Wnt3a
      results in nuclear accumulation of endogenous Dsh protein. CONCLUSIONS: These
      findings suggest that nuclear localization of Dsh is required for its function in
      the canonical Wnt/beta-catenin signaling pathway. We discuss the relevance of
      these findings to existing models of Wnt signal transduction to the nucleus.

PMID- 15720725
TI  - Optimal sampling of MRI slices for the assessment of knee cartilage volume for
      cross-sectional and longitudinal studies.
AB  - BACKGROUND: MRI slices of 1.5 mm thickness have been used in both cross sectional
      and longitudinal studies of osteoarthritis, but is difficult to apply to large
      studies as most techniques used in measuring knee cartilage volumes require
      substantial post-image processing. The aim of this study was to determine the
      optimal sampling of 1.5 mm thick slices of MRI scans to estimate knee cartilage
      volume in males and females for cross-sectional and longitudinal studies.
      METHODS: A total of 150 subjects had a sagittal T1-weighted fat-suppressed MRI
      scan of the right knee at a partition thickness of 1.5 mm to determine their
      cartilage volume. Fifty subjects had both baseline and 2-year follow up MRI
      scans. Lateral, medial tibial and patellar cartilage volumes were calculated with
      different samples from 1.5 mm thick slices by extracting one in two, one in
      three, and one in four to compare to cartilage volume and its rate of change.
      Agreement was assessed by means of intraclass correlation coefficient (ICC) and
      Bland & Altman plots. RESULTS: Compared to the whole sample of 1.5 mm thick
      slices, measuring every second to fourth slice led to very little under or over
      estimation in cartilage volume and its annual change. At all sites and subgroups,
      measuring every second slice had less than 1% mean difference in cartilage volume
      and its annual rate of change with all ICCs > or = 0.98. CONCLUSION: Sampling
      alternate 1.5 mm thick MRI slices is sufficient for knee cartilage volume
      measurement in cross-sectional and longitudinal epidemiological studies with
      little increase in measurement error. This approach will lead to a substantial
      decrease in post-scan processing time.

PMID- 15720726
TI  - Quality of life in patients with personality disorders seen at an ordinary
      psychiatric outpatient clinic.
AB  - BACKGROUND: Epidemiological studies have found reduced health-related quality of
      life (QoL) in patients with personality disorders (PDs), but few clinical studies
      have examined QoL in PDs, and none of them are from an ordinary psychiatric
      outpatient clinic (POC). We wanted to examine QoL in patients with PDs seen at a
      POC, to explore the associations of QoL with established psychiatric measures,
      and to evaluate QoL as an outcome measure in PD patients. METHODS: 72 patients
      with PDs at a POC filled in the MOS Short Form 36 (SF-36), and two established
      psychiatric self-rating measures. A national norm sample was compared on the SF
      36. An independent psychiatrist diagnosed PDs and Axis-I disorders by structured
      interviews and rated the Global Assessment of Functioning (GAF). All measurements
      were repeated in the 39 PD patients that attended the 2 years follow-up
      examination. RESULTS: PD patients showed high co-morbidity with other PDs and
      Axis I mental disorders, and they scored significantly lower on all the SF-36
      dimensions than age- and gender-adjusted norms. Adjustment for co-morbid Axis I
      disorders had some influence, however. The SF-36 mental health, vitality, and
      social functioning were significantly associated with the GAF and the self-rated
      psychiatric measures. Significant changes at follow-up were found in the
      psychiatric measures, but only on the mental health and role-physical of the SF
      36. CONCLUSION: Patients with PDs seen for treatment at a POC have globally poor
      QoL. Both physical and mental dimensions of the SF-36 are correlated with
      established psychiatric measures in such patients, but significant changes in
      these measures are only partly associated with changes in the SF-36 dimensions.

PMID- 15720727
TI  - Muscle oxidative metabolism accelerates with mild acidosis during incremental
      intermittent isometric plantar flexion exercise.
AB  - BACKGROUND: It has been thought that intramuscular ADP and phosphocreatine (PCr)
      concentrations are important regulators of mitochondorial respiration. There is a
      threshold work rate or metabolic rate for cellular acidosis, and the decrease in
      muscle PCr is accelerated with drop in pH during incremental exercise. We tested
      the hypothesis that increase in muscle oxygen consumption (o2mus) is accelerated
      with rapid decrease in PCr (concomitant increase in ADP) in muscles with drop in
      pH occurs during incremental plantar flexion exercise. METHODS: Five male
      subjects performed a repetitive intermittent isometric plantar flexion exercise
      (6-s contraction/4-s relaxation). Exercise intensity was raised every 1 min by
      10% maximal voluntary contraction (MVC), starting at 10% MVC until exhaustion.
      The measurement site was at the medial head of the gastrocnemius muscle. Changes
      in muscle PCr, inorganic phosphate (Pi), ADP, and pH were measured by 31P
      magnetic resonance spectroscopy. o2mus was determined from the rate of decrease
      in oxygenated hemoglobin and/or myoglobin using near-infrared continuous wave
      spectroscopy under transient arterial occlusion. Electromyogram (EMG) was also
      recorded. Pulmonary oxygen uptake (o2pul ) was measured by the breath-by-breath
      gas analysis. RESULTS: EMG amplitude increased as exercise intensity progressed.
      In contrast, muscle PCr, ADP, o2mus, and o2pul did not change appreciably below
      40% MVC, whereas above 40% MVC muscle PCr decreased, and ADP, o2mus, and o2pul
      increased as exercise intensity progressed, and above 70% MVC, changes in muscle
      PCr, ADP, o2mus, and o2pul accelerated with the decrease in muscle pH (~6.78).
      The kinetics of muscle PCr, ADP, o2mus, and o2pul were similar, and there was a
      close correlation between each pair of parameters (r = 0.969~0.983, p < 0.001).
      CONCLUSION: With decrease in pH muscle oxidative metabolism accelerated and
      changes in intramuscular PCr and ADP accelerated during incremental intermittent
      isometric plantar flexion exercise. These results suggest that rapid changes in
      muscle PCr and/or ADP with mild acidosis stimulate accelerative muscle oxidative
      metabolism.

PMID- 15720728
TI  - Australia's international health relations in 2003.
AB  - A survey for the year 2003 of significant developments in Australia's official
      international health relations, and their domestic ramifications, is presented.
      The discussion is set within the broader context of Australian foreign policy.
      Sources include official documents, media reports and consultations with officers
      of the Department of Health and Ageing responsible for international linkages.

PMID- 15720729
TI  - The Arabidopsis Mei2 homologue AML1 binds AtRaptor1B, the plant homologue of a
      major regulator of eukaryotic cell growth.
AB  - BACKGROUND: TOR, the target of the antibiotic rapamycin in both yeast and
      mammalian cells, is a potent cell growth regulator in all eukaryotes. It acts
      through the phosphorylation of downstream effectors that are recruited to it by
      the binding partner Raptor. In Arabidopsis, Raptor activity is essential for
      postembryonic growth. Though comparative studies suggest potential downstream
      effectors, no Raptor binding partners have been described in plants. RESULTS:
      AtRaptor1B, a plant Raptor homologue, binds the AML1 (Arabidopsis Mei2-like 1)
      protein in a yeast two-hybrid assay. This interaction is mediated by the N
      terminal 219 residues of AML1, and marks AML1 as a candidate AtTOR kinase
      substrate in plants. The AML1 N-terminus additionally carries transcriptional
      activation domain activity. Plants homozygous for insertion alleles at the AML1
      locus, as well as plants homozygous for insertion alleles at all five loci in the
      AML gene family, bolt earlier than wild-type plants. CONCLUSION: AML1 interacts
      with AtRaptor1B, homologue of a protein that recruits substrates for
      phosphorylation by the major cell-growth regulator TOR. Identification of AML1 as
      a putative downstream effector of TOR gives valuable insights into the plant
      specific mode of action of this critical growth regulator.

PMID- 15720731
TI  - PITTCON 2005.

PMID- 15720730
TI  - Evaluation of toxic agent effects on lung cells by fiber evanescent wave
      spectroscopy.
AB  - Biochemical changes in living cells are detected using a fiber probe system
      composed of a single chalcogenide fiber acting as both the sensor and
      transmission line for infrared optical signals. The signal is collected via
      evanescent wave absorption along the tapered sensing zone of the fiber. We
      spectroscopically monitored the effects of the surfactant Triton X-100, which
      serves as a toxic agent simulant on a transformed human lung carcinoma type II
      epithelial cell line (A549). We observe spectral changes between 2800-3000 cm(-1)
      in four absorptions bands, which are assigned to hydrocarbon vibrations of
      methylene and methyl groups in membrane lipids. Comparison of fiber and
      transmission spectra shows that the present technique allows one to locally probe
      the cell plasma membrane in the lipid spectral region. These optical responses
      are correlated with cellular metabolic activity measurements and LDH (lactate
      dehydrogenase) release assays that indicate a loss of cellular function and
      membrane integrity as would be expected in response to the membrane solubilizing
      Triton. The spectroscopic technique shows a significantly greater detection
      resolution in time and concentration.

PMID- 15720732
TI  - Laminar fluid diffusion interface preconditioning of serum and urine for reagent
      free infrared clinical analysis and diagnostics.
AB  - A number of reagent-free infrared spectroscopic diagnostic and analytical methods
      have been established previously making use of dry biofluid films. For example,
      this approach has successfully measured high concentration analytes of serum and
      urine. However, a number of low concentration diagnostically relevant analytes
      presently elude detection by infrared spectroscopy. This is due in part to their
      relatively low concentration and in part to spectral interference by other
      strongly absorbing constituents. The applicability of the technique would be
      broadened substantially if it were possible to concentrate and separate lower
      concentration analytes, e. g., serum creatinine and urine proteins, from the
      obscuring presence of relatively high concentration compounds. One possible means
      to achieve this is through microfluidic sample preconditioning based on laminar
      fluid diffusion interfaces. The objective of this study was therefore to
      qualitatively assess the performance of this technology in preferentially
      separating certain serum and urine analytes of clinical interest that presently
      lie just below the threshold of detection by infrared spectroscopy. Observations
      from simulated and genuine urine and serum samples strongly suggest that this
      process should improve existing accuracy and extend the range of detectable
      analytes.

PMID- 15720733
TI  - Monitoring of a pharmaceutical nanomilling process using grating light reflection
      spectroscopy.
AB  - An optical diagnostic method, grating light reflection spectroscopy (GLRS), has
      been demonstrated for the in situ monitoring of properties of heterogeneous
      matrices in industrial processes. The technique is based on measurements near the
      critical points of intensity and phase in waves reflected from a transmission
      diffraction grating in contact with a diagnostic sample. The features contained
      in the reflection spectrum near these thresholds allow for the simultaneous
      determination of the real and imaginary parts of the dielectric function of the
      sample. Using these data, the milling progress of highly concentrated fluid
      suspensions is observed as the material is milled from approximately 40 mm to 160
      nm in diameter. A theoretical model that closely resembles experimentally
      determined spectra was constructed and applied in combination with principal
      components analysis (PCA) to demonstrate that GLRS can be used to closely monitor
      changes in the mean particle size of the nanomilled drug product.

PMID- 15720735
TI  - Fourier transform infrared attenuated total reflection analysis of human hair:
      comparison of hair from breast cancer patients with hair from healthy subjects.
AB  - A comparative study of Fourier transform infrared attenuated total reflection
      (FTIR-ATR) spectra of 32 scalp and pubic hair samples from individuals diagnosed
      with breast cancer and those who were negative for breast cancer showed increases
      in the beta-sheet/disorder structures (relative to alpha-helix structures) and C
      H lipid content of hair from breast cancer patients. Thus, the presence of breast
      cancer appears to alter the hair growth process, resulting in changes in the
      composition and conformation of cell membrane and matrix materials of hair fiber.
      These appear to be consistent with the changes observed in X-ray diffraction
      patterns for hair from breast cancer patients. A blind study of 12 additional
      hair samples using these FTIR-ATR spectral differences as markers correctly
      identified all four hair samples from cancer patients (100%). Two of these
      samples were from breast cancer patients. Of the remaining two samples analyzing
      positive for cancer, one was from a prostate cancer patient and one from a lung
      cancer patient. Thus, it appears that the mechanism that alters hair fiber
      synthesis in the three types of cancer may be similar. The blind study
      incorrectly identified as positive for cancer three hair samples from two
      apparently healthy individuals and one patient considered cured from prostate
      cancer.

PMID- 15720736
TI  - In Situ Fourier transform infrared spectroscopic study of the thermal degradation
      of isotactic poly(propylene).
AB  - The conformational change of isotactic poly(propylene) (iPP) during the thermal
      degradation process has been carefully studied by in situ Fourier transform
      infrared (FT-IR) spectroscopy. This new method of studying thermal degradation of
      iPP not only shows the conventional kinetic parameter information of thermal
      degradation such as the degradation activation energy DeltaE and the degradation
      factor n, which are in accord with the results of traditional thermogravimetry
      experiments, but also indicates that many significant molecular structure changes
      occur during the thermal degradation process that come from some characteristic
      absorption band changes of in situ FT-IR. A multivariate approach, principal
      components analysis (PCA), is applied to the analysis of infrared (IR) data, and
      the results further confirm the multi-step processes of the thermal degradation
      of iPP. Above all, this is a new application to polymer thermal degradation by in
      situ FT-IR that connects the intermediate conformational change with final
      results during thermal degradation.

PMID- 15720737
TI  - Specular reflection and diffuse reflectance spectroscopy of soils.
AB  - Studies on the occurrence and effects of specular reflection in midinfrared
      spectra of soils have shown that distortions due to specular reflection occur for
      both organic (humic acid) and non-organic fractions (carbonates, silica, ashed
      fraction of soil). The results explain why the spectra of CaCO(3) in limed soils
      do not match published spectra and offer an explanation as to why the presence of
      inorganic C interferes with the development of calibrations for organic C. These
      results may also have implications for the use of mid-infrared spectra for
      quantitative and qualitative analysis of soils. For example, libraries of spectra
      collected by means other than diffuse reflectance would be largely useless for
      comparing mineral spectra to soil spectra. To obtain the best results with
      forages and grains, it is necessary to develop separate calibrations for
      different products, but this has not seemed to be a problem for diverse sets of
      soil samples with C contents of 0 to 5%. Mid-infrared calibrations have also
      appeared to be more robust than the corresponding near-infrared calibrations in
      that fewer outliers are found. However, the results discussed here indicate that
      at least for some soil types (e. g., large differences in mineralogy or C
      contents), separate calibrations may be necessary.

PMID- 15720738
TI  - Multivariate analysis of infrared spectra for monitoring and understanding the
      kinetics and mechanisms of adsorption processes.
AB  - Water adsorption onto thin zeolite 3A wafers has been investigated as a function
      of time, water vapor concentration, and zeolite sample mass using mid-infrared
      spectroscopy coupled with multivariate data analysis. Principal component
      analysis (PCA) of the spectral region of the water combination band was used for
      quantitative characterization of water adsorption onto the zeolite. The kinetics
      of the adsorption of water are found to be very reproducible and nearly linear
      with time. The kinetics of water adsorption based on data from different masses
      of zeolite are consistent with a diffusion/immobilization model for which the
      interparticle diffusion rate is comparable to the rate of adsorption. The
      infrared zeolite bands (1340-1550 cm(-1)) change during the adsorption process
      and yield more detail about the adsorption sites of the material. PCA applied to
      the zeolite bands was not directly interpretable. However, multivariate curve
      resolution applied to the spectral region containing the zeolite bands readily
      demonstrates that zeolite 3A has three water adsorption sites or environments
      that are sequentially occupied. Potential explanations for the observations of
      the multivariate curve resolution (MCR) analysis of these infrared (IR) kinetic
      adsorption experiments are presented. The explanation most consistent with our
      data suggests that water adsorbs sequentially on the zeolite to form single,
      double, and triple water adsorption on single zeolite adsorption sites. The
      combination of infrared spectroscopy and multivariate analysis is therefore
      demonstrated to be a powerful method to study detailed adsorption kinetics and
      mechanisms of the adsorption of molecules onto surfaces.

PMID- 15720739
TI  - Near-infrared spectra of Penicillium camemberti strains separated by extended
      multiplicative signal correction improved prediction of physical and chemical
      variations.
AB  - Different methods for spectral preprocessing were compared in relation to the
      ability to distinguish between fungal isolates and growth stages for Penicillium
      camemberti grown on cheese substrate. The best classification results were
      obtained by temperatureand wavelength-extended multivariate signal correction
      (TWEMSC) preprocessing, whereby three patterns of variation in nearinfrared (NIR)
      log(1/R) spectra of fungal colonies could be separated mathematically: (1)
      physical light scattering and its wavelength dependency, (2) differences in light
      absorption of water due to varying sample temperature, etc., and (3) differences
      in light absorption between different fungal isolates. With this preprocessing,
      discriminant partial least squares (PLS) regression yielded 100% correct
      classification of three isolates, both within the cross-validated calibration set
      and in two independent test sets of samples.

PMID- 15720740
TI  - Implementation of LOCAL algorithm with near-infrared spectroscopy for compliance
      assurance in compound feedingstuffs.
AB  - Seven thousand four hundred and twenty-three compound feed samples were used to
      develop near-infrared (NIR) calibrations for predicting the percentage of each
      ingredient used in the manufacture of a given compound feedingstuff. Spectra were
      collected at 2 nm increments using a FOSS NIRSystems 5000 monochromator. The
      reference data used for each ingredient percentage were those declared in the
      formula for each feedingstuff. Two chemometric tools for developing NIRS
      prediction models were compared: the so-called GLOBAL MPLS (modified partial
      least squares), traditionally used in developing NIRS applications, and the more
      recently developed calibration strategy known as LOCAL. The LOCAL procedure is
      designed to select, from a large database, samples with spectra resembling the
      sample being analyzed. Selected samples are used as calibration sets to develop
      specific MPLS equations for predicting each unknown sample. For all predicted
      ingredients, LOCAL calibrations resulted in a significant improvement in both
      standard error of prediction (SEP) and bias values compared with GLOBAL
      calibrations. Determination coefficient values (r(2)) also improved using the
      LOCAL strategy, exceeding 0.90 for most ingredients. Use of the LOCAL algorithm
      for calibration thus proved valuable in minimizing the errors in NIRS calibration
      equations for predicting a parameter as complex as the percentage of each
      ingredient in compound feedingstuffs.

PMID- 15720741
TI  - Development of a simple algorithm for the detection of chilling injury in
      cucumbers from visible/near-infrared hyperspectral imaging.
AB  - Hyperspectral images of cucumbers under a variety of conditions were acquired to
      explore the potential for the detection of chilling-induced damage in whole
      cucumbers. Region of interest (ROI) spectral features of chilling injured areas,
      resulting from chilling treatment at 0 degrees C, showed the reduction of
      reflectance intensity over the period at post-chilling room temperature (RT)
      storage. A large spectral difference between good, smooth skins and chilling
      injured skins occurred in the 700-850 nm visible/near-infrared (NIR) region. Both
      simple band ratio algorithms and principal component analysis (PCA) were
      attempted to discriminate the ROI spectra of good cucumber skins from those of
      chilling injured ones. Results revealed that both the dual-band ratio algorithm
      (R(811nm)/R(756nm)) and a PCA model from a narrow spectral region of 733-848 nm
      can detect chilling-injured skins with a success rate of over 90%. The results
      also suggested that chilling injury is relatively difficult to detect at the
      initial post-chilling RT stage, especially during the first 0-2 days in storage,
      due to insignificant manifestation of chilling induced symptoms.

PMID- 15720742
TI  - Near-infrared spectroscopic study of the physical and mechanical properties of
      wood with meso- and micro-scale anatomical observation.
AB  - Estimation of the density along with the tensile strength of wood within both the
      elastic and plastic deformation ranges, represented as modulus of elasticity
      (MOE) and ultimate tensile stress (UTS), respectively, were performed using near
      infrared (NIR) spectroscopy. A partial least squares (PLS) analysis was applied
      to the measurements of density, MOE, and UTS, and resulted in a high accuracy of
      prediction, independent of wood species. The correlation coefficient between the
      NIR spectra and criterion variables, and the regression vector resulting from the
      PLS analysis, suggested that the characteristic absorption bands were strongly
      related to the predictability of each property. In the case of softwood,
      absorption bands due to intra-molecular hydrogen-bonded OH groups in the
      crystalline regions of cellulose, which are oriented preferentially in a
      direction parallel to the cellulose chain, might strongly affect the tensile
      strength of softwood. Hardwoods have much more complex and variable structures
      than softwoods; therefore, it was supposed that the key factor governing the
      tensile strength in hardwood would be the interaction between the three principal
      constituents (i. e., cellulose, hemicellulose, and lignin) of wood.

PMID- 15720743
TI  - Optical characterization of varnish films by spectroscopic ellipsometry for
      application in artwork conservation.
AB  - The specific aim of this paper is to measure the optical constants of fresh
      varnish layers up to a thickness of 10 mum by spectroscopic ellipsometry. It is
      the first time that this technique has been used in artwork conservation and it
      may prove very promising due to its nondestructive character. Samples of fresh
      dammar varnish (natural resin) and Paraloid B72 (synthetic resin) applied on
      glass and carbon black acrylic paint were analyzed. Both varnishes were
      considered as perfect dielectrics, and the real part of their refractive index
      was described by the Cauchy model: n (lambda) = A + B/lambda(2) + C/lambda(4).
      The Cauchy coefficients for dammar varnish and Paraloid B72 were then determined
      for layers of known thickness. The ellipsometric data were fitted to a model,
      which includes a mixed varnish-air layer. The optical properties of this layer
      were calculated by the Bruggeman effective medium approximation. In the case of
      carbon black acrylic paint, another mixed layer (paint-varnish) was added to the
      model. The results are very close to the values given in the literature. Given
      the measurement reproducibility, the results show that ellipsometry can
      discriminate between dammar varnish and Paraloid B72. This is very important in
      artwork conservation studies, because it has been done by time-consuming,
      destructive techniques up to now. Future work includes measurements of other
      types of natural and synthetic varnishes, in an attempt to introduce a
      nondestructive method for picture varnish identification and aging studies.

PMID- 15720744
TI  - Rapid forensic analysis and identification of ''lilac'' architectural finishes
      using Raman spectroscopy.
AB  - The potential of Raman spectroscopy to discriminate between architectural
      finishes (household paint) has been investigated using a test set of 51 ''lilac''
      paints and three different excitation wavelengths. The spectra obtained with
      visible excitation typically displayed a series of intense Raman bands on a
      featureless fluorescence background but the spectra of all the paints studied had
      essentially identical bands. With 785 nm excitation, although the same bands that
      dominated the 514 nm spectra were still observed, other bands with comparable
      intensity also appeared. The two strongest scattering constituents were
      identified as a dioxazine dye, Violet 23 and beta-Cu(phthalocyanine). A scatter
      plot of the intensities of marker bands for these constituents (normalized to the
      strong rutile bands that were always present) showed that, despite the fact that
      the sample set spanned a wide range of rutile : dioxazine dye : phthalo- cyanine
      ratios, many of the samples had very similar ratios and could not be
      discriminated. However, all the samples (even those with similar relative
      proportions of the main constituents) could be discriminated on the basis of
      their minor constituents, either by manually measuring band intensities or
      through the creation and searching of spectral libraries.

PMID- 15720745
TI  - In situ Raman analysis of gas formation in NiMH batteries.
AB  - In this paper Raman spectrometry is introduced in the field of sealed battery
      research for in situ gas-phase analysis and for longterm measurements. For this
      purpose, a new method was successfully applied in order to model battery behavior
      without interfering with operation. It is shown that oxygen, hydrogen, and
      nitrogen are responsible for the pressure increase that occurs during
      overcharging. The relative contribution of the different gases depends on the
      current imposed on the battery as well as the operating temperature. Reproducible
      and stable signals could be obtained even under severe conditions such as high
      pressure and elevated temperature. Oxygen and hydrogen are produced in side
      reactions taking place during battery operation. However, as nitrogen is unlikely
      to be a reacting gas inside the battery, the change in its partial pressure can
      be attributed to electrode expansion and a change in the electrolyte volume.

PMID- 15720746
TI  - Atomic hydrogen emission induced by TEA CO(2) laser bombardment on solid samples
      at low pressure and its analytical application.
AB  - Hydrogen emission has been studied in laser plasmas by focusing a TEA CO(2) laser
      (10.6 microm, 500 mJ, 200 ns) on various types of samples, such as glass, quartz,
      black plastic sheet, and oil on copper plate sub-target. It was found that
      H(alpha) emission with a narrow spectral width occurs with high efficiency when
      the laser plasma is produced in the low-pressure region. On the contrary, the
      conventional well-known laser-induced breakdown spectroscopy (LIBS), which is
      usually carried out at atmospheric air pressure, cannot be applied to the
      analysis of hydrogen as an impurity. By combining low-pressure laser-induced
      plasma spectroscopy with laser surface cleaning, a preliminary quantitative
      analysis was made on zircaloy pipe samples intentionally doped with hydrogen. As
      a result, a good linear relationship was obtained between H(alpha) emission
      intensity and its concentration.

PMID- 15720747
TI  - Development of a universal ellipsoidal mirror device for fluorescence detected
      circular dichroism: elimination of polarization artifacts.
AB  - We have developed an ellipsoidal mirror fluorescence detected circular dichroism
      (FDCD) device with enhanced detection sensitivity that eliminates the
      polarization artifact; this is applicable to samples with strongly polarized
      fluorescence. The device, JASCO FDCD465, has an ellipsoidal mirror structure with
      a framework consisting of three mirrors (one elliptical and two plane mirrors)
      that maximally collects light in the FDCD. All assemblies on the device including
      the ellipsoidal mirror, cylindrical cell, and photomultiplier tube (PMT) are
      aligned on the chamber-fitting sample mount as an attachment compatible with a
      standard CD spectropolarimeter. The new FDCD465 device eliminates the
      polarization artifact caused by anisotropic distribution of the emitted light. It
      represents a convenient, reliable, and sensitive FDCD attachment to the JASCO J
      800 CD spectrometer series that can be used under both isotropic and
      photoselected conditions.

PMID- 15720748
TI  - Solid-matrix fluorescence quenching of benzo[e]pyrene and (+/-)-anti-dibenzo[a,
      l]pyrene diolepoxide-DNA adducts.
AB  - The solid-matrix fluorescence (SMF) quenching of benzo[e]pyrene and (+/-)-anti
      dibenzo[a, l]pyrene-11,12-diol-13,14-epoxide ((+/-)-antiDB[a, l]PDE)-DNA adducts
      with thallium nitrate (TlNO(3)) and sodium iodide (NaI) was examined and several
      SMF quenching models were developed. The SMF quenching data for B[e]P with either
      TlNO(3) or NaI fit a two-independent-binding-site model. However, the SMF
      quenching of (+/-)-anti-DB[a, l]PDE-DNA adducts with TlNO(3) fits a sphere of
      action model, but quenching with NaI was modeled with the two-independent-binding
      site model. The data were compared with earlier SMF quenching data for 7,8,9,10
      tetrahydroxytetrahydro-benzo[a]pyrene (tetrol I-1) and (+/-)-anti-benzo[a]pyrene
      trans-7,8-dihydrodiol-9,10-epoxide ((+/-)-anti-BPDE)DNA adducts. The
      interpretation of the SMF quenching data for the (+/-)-anti-DB[a, l]PDE-DNA
      adducts was distinctively different than the interpretation of the SMF quenching
      data for the (+/-)-antiBPDE-DNA adducts. This initial study shows that SMF
      quenching has the potential to characterize polycyclic aromatic hydrocarbonDNA
      adducts with different numbers of aromatic rings. In addition, the data indicated
      that external and intercalated DNA adducts interacted with heavy-atom salts in
      dissimilar fashions. The new SMF methodology developed is useful for the
      characterization of both polycyclic aromatic hydrocarbon-DNA adducts and
      metabolites from polycyclic aromatic hydrocarbons.

PMID- 15720749
TI  - Absorption and fluorescence spectroscopic study on complexation of Oxazine 1 Dye
      by calix[8]arenesulfonate.
AB  - It has been established by combined absorption and fluorescence measurements that
      the cationic dye Oxazine 1 (OX) and the polyvalent anionic host
      calix[8]arenesulfonate (SCA8) form two complexes in simultaneous reactions: OX +
      SCA8 <--> OX.SCA8 (1), and OX.SCA8 + OX <--> OX(2).SCA8 (2). The equilibrium
      constants for the two reactions, as functions of the ionic strength (I), and the
      absorption and fluorescence spectra of the two complex species have been
      determined by a least-squares fitting method from the experimental data. The
      variations of the binding constants with the ionic strength could be described on
      the basis of Debye-Huckel theory. The equilibrium constants are large; their
      values extrapolated to I = 0 are K(1) = 5.5 x 10(6) M(-1) and K(2) = 4.4 x 10(5)
      M(-1). The fluorescence of OX undergoes a strong static quenching upon
      complexation. These results indicate that the complexes are held together by
      strong electrostatic forces. The addition of non-fluorescent tetramethylammonium
      chloride to OX-SCA8 mixtures results in a dramatic fluorescent enhancement, which
      demonstrates the potential applicability of this supramolecular system in
      fluorescence assays.

PMID- 15720750
TI  - Effect of hydration on band intensities in diffuse infrared spectra of samples in
      alkali halide matrices.

PMID- 15720754
TI  - Fourier transform infrared imaging of human hair with a high spatial resolution
      without the use of a synchrotron.
AB  - The cross-section of a human hair has been imaged for the first time using the
      micro attenuated total reflection (ATR) Fourier transformed infrared (FT-IR)
      method in combination with a focal plane array (FPA) detector. A rigorous
      approach was applied to determine the spatial resolution, namely, measuring the
      distance over which the band absorbance changes from 95 to 5% of the maximum
      absorbance when passing through a sharp interface. The measured value for IR
      transmission was approximately 16 microm, while the value obtained using ATR
      imaging was approximately 5 microm. The enhanced spatial resolution achieved by
      this method allows the medulla of the hair (approximately 8 microm in diameter)
      to be imaged clearly without the need for a synchrotron source. The spatial
      resolution of transmission and ATR imaging is compared, and advantages of ATR
      imaging are discussed.

PMID- 15720755
TI  - New developments in planar array infrared spectroscopy.
AB  - A planar array infrared (PA-IR) spectrograph offers several advantages over other
      infrared approaches, including high acquisition rate and sensitivity. However, it
      suffers from some important drawbacks, such as a limited spectral range and a
      significant curvature of the recorded spectral images, which still need to be
      addressed. In this article, we present new developments in PA-IR spectroscopy
      that overcome these drawbacks. First, a data processing method for the correction
      of the curvature observed in the spectral images has been developed and refined.
      In addition, a dual-beam instrument that allows the simultaneous recording of two
      independent spectral images has been developed. These two improvements have been
      combined to demonstrate the real-time background correction capability of PA-IR
      instruments. Finally, the accessible spectral range of the PA-IR spectrograph has
      been extended to cover simultaneously the methylene stretching (3200-2800 cm(-1))
      and the finger-print (2000-1000 cm(-1)) spectral regions.

PMID- 15720756
TI  - Blind source separation of photoacoustic depth profiles into independent
      components.
AB  - Step-scan photoacoustic spectroscopy is a powerful tool to nondestructively
      retrieve depth related information from a sample. Through digital signal
      processing a series of spectra with effectively different modulation frequencies,
      probing different thermal diffusion lengths within a sample, can be collected
      simultaneously. For layered samples spectra of the constituent layers can then be
      obtained by calculating spectra at specific phase angles from the in-phase and
      quadrature data through phase projection. However, without prior knowledge of the
      spectra of the constituent layers, this approach can be difficult. In this report
      we present an alternate possibility for evaluating step scan photoacoustic data,
      namely independent component analysis (ICA), which allows for ''blind
      separation'' of the mixed photoacoustic spectra without prior knowledge of the
      constituent spectra. Phase projection and ICA are applied to photoacoustic data
      acquired from a multilayer sample in an attempt to isolate the spectra of the
      constituent layers. The results for the two methods are comparable, with ICA
      offering the advantage that no prior information about the pure spectra of the
      sample layers is needed.

PMID- 15720757
TI  - Statistical design of experiments: study of cross-linking process through the
      phase-resolved photoacoustic method as a multivariable response.
AB  - This work presents an add-on result of cross-linking using photoacoustic
      spectroscopy (PAS) phases in a multivariable process using the phase-resolved
      photoacoustic (PRPA) method. The method is tested to separate contributions from
      groupings -OH, -CH(2)-, -CH(3), and Si-OH overtones in the range from 700 to 2600
      nm. Samples of the copolymers ethylene vinyltrimethoxysilane (EVS) and grafted
      vinyltrimethoxysilane (VTS) on low-density polyethylene (LDPE) were prepared
      having concentrations (C) of 3, 5, and 7% of catalyst and temperatures (T) of 70,
      80, and 90 degrees C. By considering the condensation reaction, the reduction of 
      OH groups is monitored. The PRPA analysis was carried out using the surface
      response methodology and results indicated the optimum point for both answers
      (signal and phase-resolved) and for both factors of interest (C, T). For the
      copolymers, it was found that C approximately (5.00 +/- 1.14)% and T
      approximately (82.4 +/- 4.3) degrees C, while for grafted LDPE PE(g) it was found
      that C approximately (4.92 +/- 0.85)% and T approximately (80.8 +/- 2.5) degrees
      C. These results agreed with the chemical analysis for gel content, which showed
      as the optimum point 5% of catalyst and temperature of 80 degrees C. Further, it
      is an advantage that the photoacoustic method allows one to per- form a
      nondestructive analysis.

PMID- 15720758
TI  - Noninvasive alcohol testing using diffuse reflectance near-infrared spectroscopy.
AB  - A diffuse reflectance near-infrared (NIR) spectrometer was evaluated as a
      noninvasive alternative to breath and blood measurements for in vivo alcohol
      testing. A hybrid partial least squares (PLS) calibration was constructed using a
      combination of in vivo and in vitro spectral data. This model was subsequently
      evaluated for its performance in quantifying alcohol concentrations in vivo using
      a prospective validation study involving subjects who did not participate in the
      calibration. The validation study entailed induction of alcohol excursions in ten
      human subjects and comparison of the noninvasive NIR alcohol measurements to
      blood and breath alcohol measurements. Blood and breath alcohol measurements were
      performed at the time of each noninvasive NIR measurement (N = 372), establishing
      the noninvasive NIR measurement standard error relative to blood alcohol at 4.9
      mg/dL (0.0049%). Assessment of the hybrid calibration model's sensitivity and
      selectivity provided strong evidence that the hybrid calibration yielded
      measurements that were both sensitive to alcohol and independent of other
      absorbing analytes in human tissue.

PMID- 15720759
TI  - Relative contributions of hemoglobin and myoglobin to near-infrared spectroscopic
      images of cardiac tissue.
AB  - Near-infrared (NIR) spectroscopic imaging is emerging as a unique tool for intra
      operative assessment of myocardial oxygenation, but quantitative interpretation
      of the images is not straightforward. One confounding factor specific to muscle
      tissue (both skeletal and cardiac) is that the visible/NIR absorbance spectrum of
      myoglobin (Mb), an intracellular O(2) storage protein, is virtually identical to
      that of hemoglobin (Hb). As a consequence, the relative contributions of Mb and
      Hb to the NIR spectra measured in vivo for blood perfused muscle tissue cannot be
      determined from the measured spectra alone. To estimate the relative
      contributions of Mb and Hb to NIR spectra and spectroscopic images, isolated pig
      hearts were perfused first with a Hb-free blood substitute (Krebs-Henseleit
      buffer; KHB) and then with a 50/50 KHB/blood mixture, with spectroscopic images
      acquired at each step. Tissue Mb levels were estimated directly from the
      measurements during KHB perfusion, and total (Mb+Hb) levels were estimated from
      the images acquired during 50/50 blood/KHB perfusion. Myoglobin accounted for 63
      +/- 11% of the total heme content during perfusion with the 50/50 mixture
      (implying that Mb would contribute 46% of the combined (Mb+Hb) NIR profile during
      whole blood perfusion), confirming that Mb contributes substantially to near
      infrared absorbance spectra of blood perfused cardiac tissue.

PMID- 15720760
TI  - Gold/palladium and silver/palladium colloids as novel metallic substrates for
      surface-enhanced Raman scattering.
AB  - New surface-enhanced Raman scattering (SERS) substrates, composed of gold or
      silver colloidal nanoparticles doped with palladium, were prepared. These novel
      colloids are stable and maintain a satisfactory SERS efficiency, even after long
      aging. The interest in doping the coinage metal nanoparticles with palladium is
      due to the well-known catalytic activity of this metal. Transmission electron
      microscopy (TEM) and ultraviolet-visible absorption spectroscopy were used to
      characterize the shape and size of the metal particles. It was found that these
      bimetallic colloidal nanoparticles have a core-shell structure, with gold or
      silver coated with palladium clusters.

PMID- 15720761
TI  - Depth profiling in diffusely scattering media using Raman spectroscopy and
      picosecond Kerr gating.
AB  - We demonstrate how pulsed laser Raman excitation (approximately 1 ps) followed by
      fast optical Kerr gating (approximately 4 ps) can be used to effectively separate
      Raman signals originating from different depths in heterogeneous diffusely
      scattering media. The diffuse scattering slows down photon propagation through
      turbid samples enabling higher depth resolution than would be obtained for a
      given instrumental time resolution in an optically transparent medium. Two types
      of experiments on two-layer systems demonstrate the ability to differentiate
      between surface and sub-surface Raman signals. A Raman spectrum was obtained of
      stilbene powder buried beneath a 1 mm over-layer of PMMA (poly(methyl
      methacrylate)) powder. The signal contrasts of the lower stilbene layer and upper
      PMMA layer were improved by factors >or=5 and >or=180, respectively, by rejecting
      the Raman component of the counterpart layer. The ability to select the Raman
      signal of a thin top surface layer in preference to those from an underlying
      diffusely scattering substrate was demonstrated using a 100 mum thick optically
      transparent film of PET (poly(ethylene terephthalate)) on top of stilbene powder.
      The gating resulted in the suppression of the underlying stilbene Raman signal by
      a factor of 1200. The experiments were performed in back-scattering geometry
      using 400 nm excitation wavelength. The experimental technique should be well
      suited to biomedical applications such as disease diagnosis.

PMID- 15720762
TI  - Design and characterization of a femtosecond fluorescence spectrometer based on
      optical Kerr gating.
AB  - Design and characterization of a general-purpose spectrometer for recording time
      resolved emission spectra of typical fluorescent species is described. The system
      is based on a high repetition rate amplified Ti : sapphire system, an optical
      Kerr shutter for gating the emission, and a polychromator plus charge-coupled
      device (CCD) detection system. Using 1 mm of liquid benzene as the Kerr medium,
      and optics designed to provide high polarization quality, emission spectra of
      dilute solutions of solutes with nanosecond lifetimes can be recorded with good
      signal-to-noise ratios. The current spectrometer uses excitation wavelengths near
      390 nm and provides spectra over the wavelength range 400-650 nm with 4 nm
      resolution and instrument response times of 450 fs (full width at half-maximum,
      FWHM). Selected applications are described to demonstrate the utility of this
      instrument.

PMID- 15720763
TI  - High-throughput single-cell fluorescence spectroscopy.
AB  - A high-throughput method for measuring single-cell fluorescence spectra is
      presented. Upon excitation with a 488 nm argon-ion laser many bacterial cells
      were imaged by a 20x microscope objective while they moved through a capillary
      tube. Fluorescence was dispersed by a transmission diffraction grating, and an
      intensified charge-coupled device (ICCD) camera simultaneously recorded the zero
      and the first orders of the fluorescence from each cell. Single-cell fluorescence
      spectra were reconstructed from the distance between zero-order and first-order
      maxima as well as the length and the pixel intensity distribution of the first
      order images. By using this approach, the emission spectrum of E. coli cells
      expressing green fluorescent protein (GFP) was reconstructed. Also, fluorescence
      spectra of E. coli cells expressing non-fluorescent apo-subunits of R
      phycoerythrin (R-PE) were recorded after incubation of the cells with
      phycoerythrobilin (PEB) chromophore. The fluorescence spectra are in good
      agreement with results obtained on the same cells using a fluorescence
      spectrometer or a fluorescence microscope. When spectra are to be acquired, this
      approach has a higher throughput, better sensitivity, and better spectral
      resolution compared to flow cytometry.

PMID- 15720764
TI  - Photon moment analysis in cells in the presence of photo-bleaching.
AB  - The photon counting histogram (PCH) analysis of the fluorescence fluctuations
      provides the molecular brightness (epsilon) and the average number of
      fluorophores (N) in an open observation volume. PCH, which is based on the
      analysis of the whole of the photon counting histogram, has been recently
      improved by taking into account the detector dead time effect, which is relevant
      at high fluorescence rates. We investigate here the possibility of quantitatively
      applying the PCH analysis in the simplified form of photon moment analysis, in
      which only the first two moments of the photon counting histogram are computed.
      We have applied this analysis to low fluorescence signals from living cells in
      the presence of cell micro-movements and molecular photo-bleaching and describe a
      simple algorithm for its routine application. The algorithm has been tested on
      Saccharomyces Cerevisiae (yeast) cells labeled with Dimethyl-pepep and Rhodamine
      6G, and Chinese Hamster Ovary (CHO) cells stably expressing the regulatory
      subunit (RII) of protein kinase A fused to the cyan-emitting variant of GFP
      (CFP). Our statistical analysis allows us to estimate the local concentrations
      and the brightness of the fluorophores in different cellular compartments
      (nucleus, membrane, and cytoplasm) despite the occurrence of microscopic cell
      movements and significant photo-bleaching.

PMID- 15720765
TI  - Skin color correction for tissue spectroscopy: demonstration of a novel approach
      with tissue-mimicking phantoms.
AB  - The application of partial least squares (PLS) regression to visible-near
      infrared (VIS-NIR) spectroscopy for modeling important blood and tissue
      parameters is generally complicated by the variation in skin pigmentation
      (melanin) across the human population. An orthogonal correction method for
      removing the influence of skin pigmentation has been demonstrated in diffuse
      reflectance spectra from two-layer tissue-mimicking phantoms. The absorption
      properties of the phantoms were defined by lyophilized human hemoglobin (bottom
      layer) and synthetic melanin (top layer). Tissue-like scattering was simulated in
      both layers with intralipid. The approach uses principal components analysis
      (PCA) loading vectors from a separate set of phantom spectra that encode the
      unwanted melanin variation to remove the effect of melanin from the test
      phantoms. The preprocessing of phantom spectra using this orthogonal correction
      method resulted in PLS models with reduced complexity and enhanced prediction
      performance. Preliminary results from a separate study that evaluates the
      feasibility of defining skin color variation in an experiment with a single human
      subject are also presented.

PMID- 15720766
TI  - Trace element analysis of scales from four populations of Norwegian Atlantic
      salmon (Salmo salar L.) for stock identification using laser ablation inductively
      coupled plasma mass spectrometry.
AB  - The pre-smolt stage of the scale of adult Norwegian Atlantic salmon from four
      populations, encompassing both farmed and wild hatchery stocks, has been analyzed
      by laser ablation inductively coupled plasma mass spectrometry (LA-HR-ICP-MS).
      The purpose of this study was to test for differences in elemental composition
      between stocks of Atlantic salmon that have lived in separate fresh water
      locations until the smoltification and natural run out or transportation to the
      sea-cages. The populations studied were from fish farms located at Bremanger and
      Sorfold, a cultivated stock from Mossa, and one wild local stock from the river
      Gaula. The following elements were included in the analytical protocol: Li, Mg,
      Ca, Cr, Mn, Fe, Zn, Sr, Ba, Pb, and U. Calcium was used as a natural internal
      standard. Classification of the analytical data is studied by multivariate
      statistical techniques such as principal component analysis (PCA). We have been
      able to delineate the population of Atlantic salmon (Salmo salar L.) from Gaula
      and Mossa from the Bremanger and the Sorfold stock based on the ten elements
      analyzed. The Bremanger and Sorfold stocks were partially delineated. The
      differences in elemental composition in the scales, which makes the delineating
      of the four stocks possible, probably reflects geological differences in the
      bedrock at the four fresh water locations experienced by the salmon during the
      pre-smolt stage.

PMID- 15720767
TI  - Speciation of chromium via laser-induced breakdown spectroscopy of ion exchange
      polymer membranes.
AB  - A new method for the speciation of ng/mL concentrations of Cr(III) and Cr(VI)
      solutions with analysis by laser-induced breakdown spectroscopy (LIBS) is
      reported. Speciation is achieved by pre-concentration of the chromium onto
      commercially available cation exchange polymer membranes. Chromium(III) is
      removed directly by cation exchange; chromium(VI) in the filtrate is reduced to
      Cr(III) and concentrated onto a second cation exchange membrane, affording
      independent measurement of both species. Large volumes of waters containing
      Cr(III) and Cr(VI) can be concentrated onto the membranes and directly analyzed
      by laser-induced breakdown spectroscopy. The estimated limit of detection
      corresponds to 500 ng of Cr on the membrane: if a solution volume of 1 L is used,
      then the detection limit corresponds to a solution concentration of 0.5 ng/mL.
      Excellent separation of the chromium species is attained. Results show that
      overall method efficiencies range from 94-116% and are independent of the matrix.
      The influence of pH has been measured, and although Cr(VI) converts to Cr(III) in
      acidic solutions, the total Cr recoveries are not appreciably influenced by pH
      over the range of natural waters (4 to 9). In addition, speciation was performed
      in the presence of a number of different cations and showed that the method is
      robust in many different and complex matrices.

PMID- 15720768
TI  - Detection of lead in soil with excimer laser fragmentation fluorescence
      spectroscopy.

PMID- 15720769
TI  - An internal standardization procedure for spectrally resolved fluorescence
      lifetime imaging.

PMID- 15720770
TI  - Temporal sequence learning, prediction, and control: a review of different models
      and their relation to biological mechanisms.
AB  - In this review, we compare methods for temporal sequence learning (TSL) across
      the disciplines machine-control, classical conditioning, neuronal models for TSL
      as well as spike-timing-dependent plasticity (STDP). This review introduces the
      most influential models and focuses on two questions: To what degree are reward
      based (e.g., TD learning) and correlation-based (Hebbian) learning related? and
      How do the different models correspond to possibly underlying biological
      mechanisms of synaptic plasticity? We first compare the different models in an
      open-loop condition, where behavioral feedback does not alter the learning. Here
      we observe that reward-based and correlation-based learning are indeed very
      similar. Machine control is then used to introduce the problem of closed-loop
      control (e.g., actor-critic architectures). Here the problem of evaluative
      (rewards) versus nonevaluative (correlations) feedback from the environment will
      be discussed, showing that both learning approaches are fundamentally different
      in the closed-loop condition. In trying to answer the second question, we compare
      neuronal versions of the different learning architectures to the anatomy of the
      involved brain structures (basal-ganglia, thalamus, and cortex) and the molecular
      biophysics of glutamatergic and dopaminergic synapses. Finally, we discuss the
      different algorithms used to model STDP and compare them to reward-based learning
      rules. Certain similarities are found in spite of the strongly different
      timescales. Here we focus on the biophysics of the different calcium-release
      mechanisms known to be involved in STDP.

PMID- 15720771
TI  - Robust reinforcement learning.
AB  - This letter proposes a new reinforcement learning (RL) paradigm that explicitly
      takes into account input disturbance as well as modeling errors. The use of
      environmental models in RL is quite popular for both offline learning using
      simulations and for online action planning. However, the difference between the
      model and the real environment can lead to unpredictable, and often unwanted,
      results. Based on the theory of H(infinity) control, we consider a differential
      game in which a "disturbing" agent tries to make the worst possible disturbance
      while a "control" agent tries to make the best control input. The problem is
      formulated as finding a min-max solution of a value function that takes into
      account the amount of the reward and the norm of the disturbance. We derive
      online learning algorithms for estimating the value function and for calculating
      the worst disturbance and the best control in reference to the value function. We
      tested the paradigm, which we call robust reinforcement learning (RRL), on the
      control task of an inverted pendulum. In the linear domain, the policy and the
      value function learned by online algorithms coincided with those derived
      analytically by the linear H(infinity) control theory. For a fully nonlinear
      swing-up task, RRL achieved robust performance with changes in the pendulum
      weight and friction, while a standard reinforcement learning algorithm could not
      deal with these changes. We also applied RRL to the cart-pole swing-up task, and
      a robust swing-up policy was acquired.

PMID- 15720772
TI  - A computational model of the functional role of the ventral-striatal D2 receptor
      in the expression of previously acquired behaviors.
AB  - The functional role of dopamine has attracted a great deal of interest ever since
      it was empirically discovered that dopamine-blocking drugs could be used to treat
      psychosis. Specifically, the D2 receptor and its expression in the ventral
      striatum have emerged as pivotal in our understanding of the complex role of the
      neuromodulator in schizophrenia, reward, and motivation. Our departure from the
      ubiquitous temporal difference (TD) model of dopamine neuron firing allows us to
      account for a range of experimental evidence suggesting that ventral striatal
      dopamine D2 receptor manipulation selectively modulates motivated behavior for
      distal versus proximal outcomes. Whether an internal model or the TD approach (or
      a mixture) is better suited to a comprehensive exposition of tonic and phasic
      dopamine will have important implications for our understanding of reward,
      motivation, schizophrenia, and impulsivity. We also use the model to help unite
      some of the leading cognitive hypotheses of dopamine function under a
      computational umbrella. We have used the model ourselves to stimulate and focus
      new rounds of experimental research.

PMID- 15720773
TI  - A hierarchical Bayesian model for learning nonlinear statistical regularities in
      nonstationary natural signals.
AB  - Capturing statistical regularities in complex, high-dimensional data is an
      important problem in machine learning and signal processing. Models such as
      principal component analysis (PCA) and independent component analysis (ICA) make
      few assumptions about the structure in the data and have good scaling properties,
      but they are limited to representing linear statistical regularities and assume
      that the distribution of the data is stationary. For many natural, complex
      signals, the latent variables often exhibit residual dependencies as well as
      nonstationary statistics. Here we present a hierarchical Bayesian model that is
      able to capture higher-order nonlinear structure and represent nonstationary data
      distributions. The model is a generalization of ICA in which the basis function
      coefficients are no longer assumed to be independent; instead, the dependencies
      in their magnitudes are captured by a set of density components. Each density
      component describes a common pattern of deviation from the marginal density of
      the pattern ensemble; in different combinations, they can describe nonstationary
      distributions. Adapting the model to image or audio data yields a nonlinear,
      distributed code for higher-order statistical regularities that reflect more
      abstract, invariant properties of the signal.

PMID- 15720777
TI  - Drug-induced block of cardiac HERG potassium channels and development of torsade
      de pointes arrhythmias: the case of antipsychotics.
AB  - The prolongation of the cardiac repolarization process, a result of the blocking
      of the Human Ether-ago-go Related Gene potassium channel, is an undesired
      accessory property shared by many pharmacological classes of non-cardiovascular
      drugs. Often the delayed cardiac repolarization process can be identified by a
      prolongation of the QT interval of the electrocardiograph. In these conditions,
      premature action potentials can trigger a dangerous polymorphic ventricular
      tachyarrhythmia, known as torsade de pointes, which occasionally can result in
      lethal ventricular fibrillation. In this work, brief descriptions of the
      electrophysiological basis of torsade de pointes and of the several
      pharmacological classes of torsadogenic drugs are given. Attention is focused on
      antipsychotics, with a deeper overview on the experimental and clinical reports
      about their torsadogenic properties.

PMID- 15720778
TI  - In-vitro evaluation of khaya and albizia gums as compression coatings for drug
      targeting to the colon.
AB  - Khaya and albizia gums were evaluated as compression coatings for target drug
      delivery to the colon using indometacin (a water insoluble drug) and paracetamol
      (a water soluble drug) as model drugs. The core tablets were compression-coated
      with 300 and 400 mg of 100% khaya gum, 100% albizia gum and a mixture of khaya
      and albizia gum (1:1). Drug release studies were carried out in 0.1(M) HCl (pH
      1.2) for 2 h, Sorensen's buffer (pH 7.4) for 3 h and then in phosphate-buffered
      saline (pH 6.8) or in simulated colonic fluid for the rest of the experiment to
      mimic the physiological conditions from the mouth to colon. The results indicated
      that khaya and albizia gums were capable of protecting the core tablet in the
      physiological environment of the stomach and small intestine, with albizia gum
      showing greater ability than khaya gum. The release from tablets coated with the
      mixture of khaya and albizia gums was midway between the two individual gums,
      indicating that there was no interaction between the gums. Studies carried out
      using rat caecal matter in phosphate-buffered saline at pH 6.8 (simulated colonic
      fluid) showed that the gums were susceptible to degradation by the colonic
      bacterial enzymes, leading to release of the drug. The results demonstrate that
      khaya gum and albizia gum have potential for drug targeting to the colon.

PMID- 15720779
TI  - Quantitative estimation of the effects of bile salt surfactant systems on insulin
      stability and permeability in the rat intestine using a mass balance model.
AB  - The oral delivery of peptides and proteins is compromised by chemical and
      proteolytic instability as well as by permeability limitations. The aim of this
      study was to delineate the relative contributions of simple bile salt and bile
      salt:fatty acid mixed micellar systems to protein stability vs permeability
      enhancement in the rat intestine. Insulin disappearance from the rat intestine
      was evaluated when administered in simple micellar systems of sodium cholate
      (NaC), sodium taurocholate (NaTC) and sodium glycocholate (NaGC), and in mixed
      micellar systems of these bile salts and linoleic acid (LA). In-vitro stability
      studies were used to evaluate the extent of insulin degradation in the different
      micellar systems. After correction for insulin degradation in all systems a mass
      balance model was used to estimate the fractions of insulin absorbed for all
      systems. Mass balance estimates for the extent of insulin absorption in control
      perfusion systems were consistent with previously reported predictions of the
      model for ileal insulin absorption. Mass balance estimates for NaGC suggested no
      significant effects on the fraction of insulin absorbed relative to control.
      However, insulin absorption was estimated to occur to a significantly greater
      extent for NaTC simple micellar systems and was coincident with increased
      permeability of the hydrophilic marker molecule PEG 4000. The mass balance model
      estimated higher fractions of insulin absorbed for all mixed micellar systems in
      line with enhanced plasma insulin levels and higher PEG 4000 permeabilities for
      these systems.

PMID- 15720780
TI  - Pharmacokinetic advantage of intraperitoneal injection of docetaxel in the
      treatment for peritoneal dissemination of cancer in mice.
AB  - Intraperitoneal administration of docetaxel has been used to treat peritoneal
      dissemination of cancer, but its safety has not yet been confirmed. We have
      compared the pharmacokinetic behaviour of docetaxel after intravenous and
      intraperitoneal administration in CD-1-nu/nu mice bearing MKN45P, a gastric
      cancer variant line producing peritoneal dissemination. Docetaxel (8 mg kg(-1))
      was intravenously or intraperitoneally injected into the mice and at designated
      times the drug concentration was measured in plasma, ascites fluid, and abdominal
      tissues (liver, kidney, intestine and spleen, solid cancer, and suspended free
      cancer). The pharmacokinetic behaviour of docetaxel was similar in control mice
      and cancer-bearing mice after administration via either route, except that the
      transfer of docetaxel from the abdominal cavity to systemic blood (plasma) was
      slower in cancerbearing mice than in control mice. As expected, the
      intraperitoneal drug concentration was much higher (approximately 100-fold) and
      was maintained for a longer time in the intraperitoneal injection group than in
      the intravenous injection group. The drug concentrations in peritoneal solid
      cancer tissue and suspended free cancer cells were also significantly higher for
      a longer time in the intraperitoneal injection group than in the intravenous
      injection group. The values of the plasma area under concentration-time curves
      (AUC) were similar for both administration routes. The ratio of AUC ascite/AUC
      plasma after intraperitoneal administration was higher than after intravenous
      administration. The drug concentration in abdominal organs after intraperitoneal
      injection was lower during the first 2 h, then became similar to those after
      intravenous injection. These results indicated that the intraperitoneal
      administration of docetaxel for peritoneal dissemination was likely to be an
      effective treatment method, without causing any increase in systemic toxicity.

PMID- 15720781
TI  - A pharmacokinetic/pharmacodynamic model for a platelet activating factor
      antagonist based on data arising from Phase I studies.
AB  - A nonlinear mixed-effects modelling approach was used to analyse pharmacokinetic
      and pharmacodynamic data from two Phase I studies of a platelet activating factor
      (PAF) antagonist under development for the treatment of seasonal allergic
      rhinitis. Data for single-dose (8 subjects) and multiple-dose (9 subjects)
      administration were available for analysis with a program based on an EM
      algorithm. Pharmacokinetic analyses of plasma drug concentrations were performed
      using a biexponential model with first-order absorption. PAF response data were
      modelled with a hyperbolic Emax model. The drug showed nonlinear
      pharmacokinetics, with the clearance decreasing from 46.0 to 27.1 L h(-1) over a
      dose range of 160-480 mg. There was an apparent dose dependency within the C50
      (concentration producing 50% of the maximum effect) but at higher doses most of
      the data was above the estimated C50 and when the data was analysed
      simultaneously a value of 17.57 ng mL(-1) was obtained for C50, with considerable
      intersubject variability (103%). Consistent results were obtained from the two
      studies and the population and individual pharmacodynamic parameter estimates
      from the analyses provided predicted responses that were in good agreement with
      the observed data. The results were used to simulate a 320-mg twice-daily dosing
      regimen.

PMID- 15720782
TI  - Fadolmidine-induced ocular hypotension in normotensive rabbits.
AB  - Fadolmidine, a novel selective alpha2-adrenoceptor agonist, was evaluated for its
      efficacy to lower intraocular pressure in normotensive rabbits (n=5-6). The dose
      response profile between 0.004 microg and 12.5 microg of fadolmidine was
      determined. The effect of pH on the partition of fadolmidine was studied in order
      to select an optimal pH for topical fadolmidine administration. After topical
      administration, fadolmidine significantly lowered the intraocular pressure in
      normotensive rabbits. The onset of action was immediate, with no initial increase
      in intraocular pressure. A significant decrease in intraocular pressure was
      already observed at 1 h after dosing. The maximum decrease in intraocular
      pressure was observed after a 2.5 microg dose of fadolmidine in both eyes at 2 h
      after dosing. The mean maximum decrease in the treated and untreated eye was 6.4
      mmHg and 3.9 mmHg, respectively. In conclusion, fadolmidine is a potent
      intraocular pressure lowering agent. In addition, fadolmidine does not cause a
      significant initial increase in intraocular pressure. Because of the strong
      dependence of the distribution coefficient on pH, the pH of the administered
      solution is important, with physiological pH being optimal in this respect.

PMID- 15720783
TI  - The changes in the endothelial expression of cell adhesion molecules and iNOS in
      the vessel wall after the short-term administration of simvastatin in rabbit
      model of atherosclerosis.
AB  - Cell adhesion molecules P-selectin, VCAM-1 and ICAM-1 play an important role in
      the pathogenesis of atherosclerosis. High levels of nitric oxide (NO) produced by
      inducible NO synthase (iNOS) have been associated with atherosclerotic processes.
      Simvastatin is an HMG-CoA reductase inhibitor responsible for many clinical
      benefits. The aim of this study was to detect and quantify changes in endothelial
      expression of P-selectin, VCAM-1, ICAM-1 and iNOS in the vessel wall after the
      shortterm administration of simvastatin in a rabbit model of atherosclerosis.
      Eighteen New Zealand White rabbits were randomly divided into three groups (n=6).
      In the cholesterol group, rabbits consumed an atherogenic diet (0.4% cholesterol)
      for eight weeks. In the simvastatin group, rabbits consumed an atherogenic diet
      for six weeks and then consumed an atherogenic diet supplemented with simvastatin
      (10 mg kg(-1)) for two weeks. Biochemical analysis showed that administration of
      simvastatin led to an almost two-fold lowering of the total serum cholesterol,
      VLDL, LDL and HDL, but not triglycerides, compared with the cholesterol-fed
      rabbits only. Stereological analysis of the immunohistochemical staining revealed
      that administration of simvastatin (10 mg kg(-1) daily) in an atherogenic diet
      decreased the endothelial expression of P-selectin, ICAM-1 and iNOS in both
      aortic arch and carotid artery compared with the cholesterol fed-rabbits only. We
      conclude that simvastatin has beneficial effects on endothelial function by
      decreasing expression of P-selectin, ICAM-1 and iNOS in endothelial cells in the
      very early stages of atherogenesis.

PMID- 15720784
TI  - In-vivo effects of the 1,2,4-piperazine derivatives MM5 and MC1, putative 5-HT
      agonists, on dopamine and serotonin release in rat prefrontal cortex.
AB  - Two 1,2,4-substituted derivatives of piperazine were tested for their effect on
      dopamine and serotonin (5-HT) release in rat prefrontal cortex. Both compounds, 1
      [4-(4-chinolin-2-yl-piperazin-1yl)-butyl]piperidin-2-on (MM5) and 1-[4-(2-methyl
      4-chinolin-2-yl-piperazin-1-yl)-butyl]-8-azaspiro [4.5]decano-7,9-dion (MC1),
      produced hypothermia in mice and showed affinity for 5-HT1A receptors in-vitro.
      Like the selective 5-HT1A agonist 8-OH-DPAT (0.1 mg kg(-1)), MM5 given
      peripherally (30 mg kg(-1)) decreased the extracellular 5-HT level in rat
      prefrontal cortex, while MC1 suppressed 5-HT release at a higher dose (40 mg kg(
      1)), but not at a lower one (30 mg kg(-1)). The effect of both compounds on 5-HT
      release was abolished by WAY 100635 (0.3 mg kg(-1)). MC1 (30 and 40 mg kg(-1)),
      but not MM5, raised cortical dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and
      extracellular homovanillic acid (HVA) levels. The effect of MC1 on dopamine
      release was reversed by neither WAY 100635 nor the non-selective 5-HT2 antagonist
      ritanserin (2 mg kg(-1)). However, ritanserin prevented the effect of the higher
      dose of MC1 on 5-HT release. The results of this study suggest that MM5 exhibits
      the profile of a 5-HT1A agonist devoid of dopaminergic activity. MC1 seems to
      possess moderate agonist activity at 5-HT1A and 5-HT2A receptors, while acting on
      5-HT release in the rat prefrontal cortex. However, the facilitation of dopamine
      release by this compound does not seem to be related to its affinity for 5-HT1A
      and 5-HT2A receptors.

PMID- 15720785
TI  - The metallopeptide antibiotic bacitracin inhibits interleukin-12 alphabeta and
      beta2 secretion.
AB  - The metalloantibiotic bacitracin is a known inhibitor of protein disulfide
      isomerase (PDI). The disulfide-linked interleukin-12 (IL-12) alphabeta
      heterodimer and beta2-homodimer forms are crucial mediators of cell-mediated
      immune responses and inflammatory reactions. Bacitracin was found to potently
      block secretion of both the alphabeta- and beta2-dimer forms of IL-12, while it
      did not affect secretion of the beta-monomer. This inhibition coincided with a
      reduction in the intracellular amount of PDI found in complex with the beta-chain
      during intracellular transit. Bacitracin did not affect mRNA levels of the
      alphabeta- and beta-chain. Similar to bacitracin, N-acetylcysteine blocked
      alphabeta- and beta2-secretion as well as PDI-beta-chain complex formation. Thus,
      blocking PDI or shifting the endoplasmic reticulum towards a more reduced status
      disrupts the oxidative folding pathway or assembly of IL-12 dimer forms. The
      assembly stage of cytokines in the endoplasmic reticulum may represent a novel
      target for pharmacological intervention.

PMID- 15720786
TI  - Synthesis of baicalein derivatives as potential anti-aggregatory and anti
      inflammatory agents.
AB  - The direct acylation of trimethoxyphenol (1) with substituted cinnamoyl chlorides
      followed by Fries rearrangement and cyclization afforded a practical route for
      the synthesis of novel baicalein derivatives 4 functionalized on the B-ring in
      good overall yields. In the methylthiazoletetrazolium bromide (MTT) assay, none
      of the synthetic polyhydroxyflavonoids were cytotoxic at concentrations up to 200
      microM on lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages over 24
      h, while in the same cells they significantly inhibited NO production. Among the
      derivatives, 4d (IC50=46.1 +/- 0.3 microM) was found to exhibit the most potent
      activity compared with N-nitro-(L)-arginine methyl ester (L-NAME, IC50 >300
      microM). Compounds 4b, 4e, 4f, 4h and 4i remarkably inhibited platelet
      aggregation induced by arachidonic acid and collagen in rabbit washed platelets
      compared with aspirin. Analysis of their structure-activity relationships
      indicated that, in the structural modification on the B-ring of baicalein (4a),
      introduction of appropriate electro-withdrawing substituents such as 2-Cl (4b), 4
      Cl (4d), and 4-phenyl (4i) notably increased the potency on the inhibition of LPS
      activated NO production and arachidonic acid- and collagen-induced aggregation.
      Baicalein itself was equally effective in the inhibition of LPS-activated NO
      production and collagen-induced aggregation but less active against arachidonic
      acid-induced aggregation. Our in-vitro results suggested that by appropriate
      structural modification of baicalein it may be possible to develop novel
      therapeutic agents against platelet-aggregation and inflammation.

PMID- 15720787
TI  - Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid
      of the medicinal herb Evodia rutaecarpa, in rats.
AB  - Rutaecarpine is a main active alkaloid present in the medicinal herb, Evodia
      rutaecarpa. The cytochrome P450 (CYP) 1A2 substrate, theophylline, is an
      important therapeutic agent for the treatment of asthma, but has a narrow
      therapeutic index. To evaluate the pharmacokinetic interaction of theophylline
      with rutaecarpine, the effects of rutaecarpine on CYP1A2 activity and
      theophylline pharmacokinetics were investigated. Oral treatment of Sprague-Dawley
      rats with 50 mg kg(-1) rutaecarpine for three days through a gastrogavage caused
      a 4- and 3-fold increase in liver microsomal 7-ethoxyresorufin O-deethylation
      (EROD) and 7-methoxyresorufin O-demethylation activity, respectively. In the
      kidney, rutaecarpine treatment caused a 3-fold increase in EROD activity. In the
      lungs, EROD activity was elevated from an undetectable to a detectable level by
      rutaecarpine. Pharmacokinetic parameters of theophylline were determined using a
      microdialysis sampling method. Rutaecarpine pre-treatment increased the clearance
      of theophylline in a dose-dependent manner. Pre-treatment of rats with 50 mg kg(
      1) rutaecarpine caused a 3-fold increase in theophylline clearance and a 70%, 68%
      and 68% decrease in the area under the concentration-time curve (AUC), mean
      residence time (MRT) and half-life, respectively. These results demonstrated that
      rutaecarpine treatment elevated CYP1A2 catalytic activity and theophylline
      excretion in rats. In patients taking theophylline, adverse effects might be
      noticed when a rutaecarpine-containing herbal preparation is used concomitantly.

PMID- 15720788
TI  - Polyphenols from plants used in traditional Indonesian medicine (Jamu): uptake
      and antioxidative effects in rat H4IIE hepatoma cells.
AB  - Phytochemical investigation of plants used in traditional Indonesian medicine
      (Jamu) yielded lignans (pinoresinol, 9 alpha-hydroxypinoresinol and
      salicifoliol), flavonoids (3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)
      glucopyranosylkaempferol, luteolin and apigenin) and coumarins (coumarin, 8
      hydroxycoumarin and 5-hydroxycoumarin). The beneficial effects of the respective
      plants for human health are thought to be associated with antioxidative activity.
      In the present study, the antioxidative capacity of the isolated compounds was
      determined in an in-vitro assay. Luteolin and kaempferol (cleavage product of 3-O
      beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol, which is
      thought to be formed in the intestine) showed strong antioxidant activity;
      pinoresinol and 9 alpha-hydroxypinoresinol showed only minor antioxidative
      effects. The coumarins, as well as apigenin and 3-O-beta-(D)-glucopyranosyl-(1-
      >6)-beta-(D)-glucopyranosylkaempferol were inactive. The antioxidative effects of
      luteolin, kaempferol and pinoresinol were further investigated in H4IIE rat
      hepatoma cells. A strong protective effect of kaempferol and luteolin was found
      against H2O2-mediated intracellular reactive oxygen species formation measured
      using the dichlorofluorescein assay and H2O2-mediated DNA strand breaks.
      Pinoresinol did not have a protective effect against H2O2-mediated DNA-damage,
      but in the dichlorofluorescein assay, an antioxidative effect was detectable.
      During studies with H4IIE cells, kaempferol, luteolin and pinoresinol were taken
      up by the cells within 60 min. The flavonoids were found to be relatively toxic
      at higher concentrations, while pinoresinol was less cytotoxic. In conclusion,
      kaempferol and luteolin, at low concentrations (< or = 50 microM), protect H4IIE
      cells against oxidative stress but are cytotoxic at higher concentrations; the
      biological effects of pinoresinol are less prominent in comparison. These results
      are important for the identification of pharmacologically active substances from
      traditional Indonesian medicinal plants.

PMID- 15720790
TI  - Effects of glucose, fructose and 5-hydroxymethyl-2-furaldehyde on the presystemic
      metabolism and absorption of glycyrrhizin in rabbits.
AB  - Our previous study reported that co-administration of honey significantly
      increased the serum levels of glycyrrhetic acid (GA) after oral administration of
      glycyrrhizin (GZ) in rabbits. The components of honey are sucrose, glucose,
      fructose and 5-hydroxymethyl-furaldehyde (HMF). To clarify the causative
      component(s) in honey that altered the metabolic pharmacokinetics of GZ, rabbits
      were given GZ (150 mg kg(-1)) with and without glucose (5 g/rabbit), fructose (5
      g/rabbit) and HMF (1 mg kg(-1)), respectively, in crossover designs. An HPLC
      method was used to determine concentrations of GZ and GA in serum as well as GA
      and 3-dehydroglycyrrhetic acid (3-dehydroGA) in faeces suspension. A
      noncompartment model was used to calculate the pharmacokinetic parameters and
      analysis of variance was used for statistical comparison. Our results indicated
      that the area under curve (AUC) of GA was significantly increased by 29% when HMF
      was coadministered, whereas the pharmacokinetics of GZ and GA were not
      significantly altered by coadministration of glucose or fructose. An in-vitro
      study, using faeces to incubate GZ and GA individually, indicated that HMF
      significantly inhibited the oxidation of GA to 3-dehydroGA and this may explain
      the enhanced GA absorption in-vivo. It was concluded that HMF is the causative
      component in honey that affects the presystemic metabolism and pharmacokinetics
      of GZ in-vivo.

PMID- 15720789
TI  - Modulatory effects of Aloe vera leaf gel extract on oxidative stress in rats
      treated with streptozotocin.
AB  - Oxidative stress is currently suggested as a mechanism underlying diabetes and
      diabetic-related complications. Oxidative stress results from an imbalance
      between radical-generating and radical-scavenging systems. Many secondary plant
      metabolites have been reported to possess antioxidant activity. This study was
      designed to evaluate the potential antioxidative activity of the ethanolic
      extract from Aloe vera leaf gel in the plasma and pancreas of streptozotocin
      (STZ)-induced diabetic rats. Glibenclamide was used as a standard reference drug.
      Oral administration of ethanolic extract at a concentration of 300 mg kg(-1) body
      weight for 21 days resulted in a significant reduction in fasting blood glucose,
      thiobarbituric acid reactive substances, hydroperoxides and alpha-tocopherol and
      significant improvement in ascorbic acid, reduced glutathione and insulin in the
      plasma of diabetic rats. Similarly, the treatment also resulted in a significant
      reduction in thiobarbituric acid reactive substances, hydroperoxides, superoxide
      dismutase, catalase and glutathione peroxidase and significant improvement in
      reduced glutathione in the pancreas of STZ-induced diabetic rats when compared
      with untreated diabetic rats. The ethanolic extract appeared to be more effective
      than glibenclamide in controlling oxidative stress. Thus, this study confirms the
      ethnopharmacological use of Aloe vera in ameliorating the oxidative stress found
      in diabetes.

PMID- 15720791
TI  - The anxiolytic-like effect of 5-HT1B receptor ligands in rats: a possible
      mechanism of action.
AB  - We have examined the effect of lesions of 5-hydroxytryptamine (5-HT) neurons,
      produced by p-chloroamphetamine (p-CA; 2 x 10 mg kg(-1)), and the influence of
      flumazenil (Ro 15-1788, 10 mg kg(-1)), a benzodiazepine receptor antagonist, on
      the anxiolytic-like activity of CP 94253 (5-propoxy-3-(1,2,3,6-tetrahydro-4
      pyridinyl)-1H-pyrrolo[3,2-b]pyridine), a 5-HT1B receptor agonist, SB 216641 (N-[3
      [3-(dimethylamino)ethoxy]-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol
      3-yl)-[1,1'-biphenyl]-4-carboxamide), a 5-HT1B receptor antagonist, and GR 127935
      (N-[4-methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4
      oxadiazol-3-yl)-l, l'-biphenyl-4-carboxamide), a 5-HT1B/1D receptor antagonist,
      in the Vogel conflict drinking test in rats. Diazepam was used as a reference
      compound. CP 94253 (2.5 mg kg(-1)), SB 216641 (2.5 mg kg(-1)), GR 127935 (10 mg
      kg(-1)) and diazepam (5 mg kg(-1)) significantly increased the number of shocks
      accepted during experimental sessions in the conflict drinking test in vehicle-
      and p-CA-pretreated rats. Flumazenil did not change the anxiolytic-like effect of
      CP 94253 (2.5 mg kg(-1)), but wholly blocked the anxiolytic-like effects of SB
      216641 (2.5 mg kg(-1)), GR 127935 (10 mg kg(-1)) and diazepam (5 mg kg(-1)). p-CA
      and flumazenil alone were inactive in the conflict drinking test. The results
      suggested that the anxiolytic-like effect of the 5-HT1B receptor ligands CP
      94253, SB 216641 and GR 127935 was possibly linked to the postsynaptic 5-HT1B
      receptors or/and 5-HT1B heteroreceptors. The results suggested also that
      benzodiazepine receptors were indirectly involved in the effects of SB 216641 and
      GR 127935 (but not of CP 94253), which might have been due to a possible
      interaction between the 5-HT and the GABA/benzodiazepine systems.

PMID- 15720792
TI  - Oleanolic acid nanosuspensions: preparation, in-vitro characterization and
      enhanced hepatoprotective effect.
AB  - Oleanolic acid is a naturally derived triterpene used clinically in the treatment
      of hepatitis in China, but its poor solubility often leads to poor
      bioavailability. In the present study, oleanolic acid nanosuspensions were
      prepared by the nanoprecipitation method and then systematically characterized.
      The average particle size of the obtained nanosuspensions was 284.9 nm, with a
      polydispersity index of 0.216. Transmission electron microscopy and atomic force
      microscopy showed that the drug existed as spherical or near-spherical
      nanoparticles in the nanosuspensions. Differential scanning calorimetry and X-ray
      diffraction studies indicated that oleanolic acid was present in an amorphous
      state in the lyophilized nanosuspensions. At 25 degrees C, the saturation
      solubility of oleanolic acid was increased by about 6 times after nanoation
      (25.72 microg mL(-1) vs 4.37 microg mL(-1)). In the in-vitro drug release
      experiments, the lyophilized nanosuspensions showed a faster drug dissolution
      rate than that of the coarse drug powder (approx. 90% vs 15% during the first 20
      min), and nearly 95% of the oleanolic acid was released by 120 min. As evidenced
      by the lower serum alanine aminotransferase activity and liver malondialdehyde
      content, pre-treatment with oleanolic acid nanosuspensions significantly enhanced
      the hepatoprotective effect of oleanolic acid against carbon tetrachloride
      induced liver injury.

PMID- 15720793
TI  - Gastroprotective activity of a new semi-synthetic solidagenone derivative in
      mice.
AB  - The gastroprotective activity of the new semi-synthetic solidagenone derivative
      15,16-epoxy8(9),13(16),14-labdatrien-7 beta-methoxy-6 beta-ol (ELMO) has been
      assessed on the model of HCl/EtOH-induced gastric lesions in mice. Human gastric
      epithelial cells (AGS) and fibroblasts (MRC-5) were used to determine its mode of
      action. The effect of ELMO on the prostaglandin E2 content, cellular reduced
      glutathione (GSH) and protection against damage induced by sodium taurocholate
      was assessed against AGS cells. The effect of ELMO on the growth of AGS and
      fibroblast cultures was evaluated. The superoxide anion scavenging capacity of
      the compound was studied also. The cytotoxicity of ELMO, expressed as cell
      viability, was assessed using two independent endpoints: neutral red uptake (NRU)
      and the reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium
      bromide (MTT) for MRC-5 fibroblasts and NRU for AGS cells. A single oral dose of
      ELMO (10 and 20 mg kg(-1)) inhibited the appearance of gastric lesions in mice
      displaying similar values to lansoprazole at 20 mg kg(-1). At 40 microM ELMO
      increased the prostaglandin E2 content but not GSH in AGS cells. The compound
      showed no effect on sodium taurocholate-induced damage and was devoid of
      superoxide anion scavenging activity. Concentrations of 0.5, 1, 2 and 4 microM
      stimulated fibroblast but not AGS cell proliferation. The compound showed weak
      cytotoxicity with values (IC50) of 411 (NRU) and 418 microM (MTT) for fibroblasts
      and 261 microM (NRU) for AGS cells. The results support further pharmacological
      study of this compound as a potential new anti-ulcerogenic drug.

PMID- 15720795
TI  - A mathematical investigation of the multiple pathways to recurrent prostate
      cancer: comparison with experimental data.
AB  - Considerable research is aimed at determining the mechanisms by which hormone
      refractory prostate cancer develops. In an effort to assist in the understanding
      of recurrent prostate cancer and the cellular processes that mediate this
      disease, a mathematical model is presented that describes both the pretreatment
      growth and the posttherapy relapse of human prostate cancer xenografts. Our goal
      is to evaluate the interplay between the multiple mechanisms that have been
      postulated as causes of androgen-independent relapse. Simulations of the model
      show that molecular events that render the androgen receptor irrelevant to
      disease progression, such as upregulation of BCL2, can result in relapse after
      androgen deprivation therapy. However, decreased apoptosis of androgen
      independent cells alone overestimates the effects of hormone therapy when
      compared to experimental data. When decreased apoptosis is combined with
      continual androgen receptor activation, the posttherapy growth dynamics are in
      excellent correlation with experimental observations of the growth of LuCaP
      xenografts. Furthermore, the mathematical model predicts that upregulation of the
      androgen receptor, together with its increased activation, is alone sufficient to
      result in the androgen-independent growth of LNCaP xenografts. Recent
      experimental studies that suggest that the posttherapy increase in and continual
      activation of the androgen receptor are common and crucial features of recurrent
      prostate cancer provide validation of the model predictions. This approach
      provides a framework for using mathematical techniques to study novel therapeutic
      strategies aimed at controlling this disease.

PMID- 15720796
TI  - Inhibition of proliferation, migration, and matrix metalloprotease production in
      malignant mesothelioma cells by tyrosine kinase inhibitors.
AB  - The epidermal growth factor receptor (EGFR) is expressed in a variety of human
      solid tumors, including malignant mesothelioma. EGFR has been implicated in
      regulation of cell proliferation, survival, angiogenesis, and metastasis, making
      it an ideal target for drug development. ZD1839 (gefitinib) and OSI-774
      (erlotinib) are new, low-molecular-weight, EGFR-selective tyrosine kinase (TK)
      inhibitors, whereas CI-1033 is a pan-EGFR family TK inhibitor. In the present
      study, we used ZD1839, OSI-774, and CI-1033 and investigated the effect of these
      drugs on proliferation, migration, and matrix metalloprotease (MMP) production in
      three malignant mesothelioma cell lines (M14K, ZL34, and SPC212). Using
      [3H]thymidine incorporation, DNA synthesis assay, we found that all three drugs
      inhibited transforming growth factor-alpha (TGF-alpha)-induced cellular
      proliferation in a dose-dependent manner. In addition, all three drugs induced
      apoptosis in ZL34 cells as determined by flow cytometry using annexin-V staining.
      Furthermore, all three drugs inhibited TGF-alpha-induced cell migration
      (chemotaxis) in a dose-dependent manner as determined by Boyden chamber assay.
      TGF-alpha-induced MMP-9 production was also inhibited in a dose-dependent manner
      as determined by gelatin zymography in three cell lines tested. In conclusion,
      our study demonstrates inhibitory effectiveness of EGFR-TK inhibitors in
      malignant mesothelioma cells and suggests that these drugs may be an effective
      treatment strategy for malignant mesothelioma.

PMID- 15720798
TI  - Multimutated herpes simplex virus g207 is a potent inhibitor of angiogenesis.
AB  - The mode of the antitumoral activity of multimutated oncolytic herpes simplex
      virus type 1 G207 has not been fully elucidated yet. Because the antitumoral
      activity of many drugs involves the inhibition of tumor blood vessel formation,
      we determined if G207 had an influence on angiogenesis. Monolayers of human
      umbilical vein endothelial cells and human dermal microvascular endothelial
      cells, but not human dermal fibroblasts, bronchial epithelial cells, and retinal
      glial cells, were highly sensitive to the replicative and cytotoxic effects of
      G207. Moreover, G207 infection caused the destruction of endothelial cell tubes
      in vitro. In the in vivo Matrigel plug assay in mice, G207 suppressed the
      formation of perfused vessels. Intratumoral treatment of established human
      rhabdomyosarcoma xenografts with G207 led to the destruction of tumor vessels and
      tumor regression. Ultrastructural investigations revealed the presence of viral
      particles in both tumor and endothelial cells of G207-treated xenografts, but not
      in adjacent normal tissues. These findings show that G207 may suppress tumor
      growth, in part, due to inhibition of angiogenesis.

PMID- 15720797
TI  - Monoclonal antibody 16D10 to the C-terminal domain of the feto-acinar pancreatic
      protein binds to membrane of human pancreatic tumoral SOJ-6 cells and inhibits
      the growth of tumor xenografts.
AB  - Feto-acinar pancreatic protein (FAPP) characterized by mAbJ28 reactivity is a
      specific component associated with ontogenesis and behaves as an oncodevelopment
      associated antigen. We attempted to determine whether pancreatic tumoral SOJ-6
      cells are expressed at their surface FAPP antigens and to examine if specific
      antibodies directed against these FAPP epitopes could decrease the growth of
      pancreatic tumors in a mice model. For this purpose, we used specific antibodies
      against either the whole FAPP, the O-glycosylated C-terminal domain, or the N
      terminal domain of the protein. Our results indicate that SOJ-6 cells expressed
      at their surface a 32-kDa peptide corresponding to the C-terminal domain of the
      FAPP. Furthermore, we show, by using endoproteinase Lys-C or geldanamycin, a drug
      able to impair the FAPP secretion, that this 32-kDa peptide expressed on the SOJ
      6 cell surface comes from the degradation of the FAPP. Finally, an in vivo
      prospective study using a preventative tumor model in nude mice indicates that
      targeting this peptide by the use of mAb16D10 inhibits the growth of SOJ-6
      xenografts. The specificity of mAb16D10 for pancreatic tumors and the possibility
      to obtain recombinant structures of mucin-like peptides recognized by mAb16D10
      and mAbJ28 are promising tools in immunologic approaches to cure pancreatic
      cancers.

PMID- 15720799
TI  - Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic
      cells during bronchial carcinogenesis.
AB  - Polycomb group (PcG) genes are responsible for maintenance of cellular identity
      and contribute to regulation of the cell cycle. Recent studies have identified
      several PcG genes as oncogenes, and a role for PcG proteins in human oncogenesis
      is suspected. We investigated the expression of BMI-1 and EZH2 PcG oncogenes in
      human bronchial squamous cell carcinomas (SCCs) and bronchial premalignant
      precursor lesions (PLs). Whereas normal bronchial epithelium was associated with
      widespread expression of BMI-1 in resting EZH2-negative cells, neoplastic cells
      in lung carcinomas displayed altered expression of both BMI-1 and EZH2. Two
      patterns of abnormal PcG expression were observed: increased expression of BMI-1
      in dividing neoplastic cells of PLs and SCCs, and enhanced expression of EZH2 and
      Ki-67 in BMI-1-positive cells according to severity of the histopathologic stage.
      We propose that altered expression of BMI-1 and EZH2 is an early event that
      precedes high rates of proliferation in lung cancer. Because PcG complexes are
      normally involved in the maintenance of cell characteristics, abnormal PcG
      expression may contribute to loss of cell identity.

PMID- 15720800
TI  - Identification and validation of commonly overexpressed genes in solid tumors by
      comparison of microarray data.
AB  - Cancers originating from epithelial cells are the most common malignancies. No
      common expression profile of solid tumors compared to normal tissues has been
      described so far. Therefore we were interested if genes differentially expressed
      in the majority of carcinomas could be identified using bioinformatic methods.
      Complete data sets were downloaded for carcinomas of the prostate, breast, lung,
      ovary, colon, pancreas, stomach, bladder, liver, and kidney, and were subjected
      to an expression analysis using SAM. In each experiment, a gene was scored as
      differentially expressed if the q value was below 25%. Probe identifiers were
      unified by comparing the respective probe sequences to the Unigene build 155
      using BlastN. To obtain differentially expressed genes within the set of analyzed
      carcinomas, the number of experiments in which differential expression was
      observed was counted. Differential expression was assigned to genes if they were
      differentially expressed in at least eight experiments of tumors from different
      origin. The identified candidate genes ADRM1, EBNA1BP2, FDPS, FOXM1, H2AFX,
      HDAC3, IRAK1, and YY1 were subjected to further validation. Using this
      comparative approach, 100 genes were identified as upregulated and 21 genes as
      downregulated in the carcinomas.

PMID- 15720801
TI  - Cell cycle phase abnormalities do not account for disordered proliferation in
      Barrett's carcinogenesis.
AB  - Barrett's esophagus (BE) epithelium is the precursor lesion for esophageal
      adenocarcinoma. Cell cycle proteins have been advocated as biomarkers to predict
      the malignant potential in BE. However, whether disruption of the cell cycle
      plays a causal role in Barrett's carcinogenesis is not clear. Specimens from the
      Barrett's dysplasia-carcinoma sequence were immunostained for cell cycle phase
      markers (cyclin D1 for G1; cyclin A for S, G2, and M; cytoplasmic cyclin B1 for
      G2; and phosphorylated histone 3 for M phase) and expressed as a proportion of
      proliferating cells. Flow cytometric analysis of the cell cycle phase of
      prospective biopsies was also performed. The proliferation status of
      nondysplastic BE was similar to gastric antrum and D2, but the proliferative
      compartment extended to the luminal surface. In dysplastic samples, the number of
      proliferating cells correlated with the degree of dysplasia (P <.001). The
      overall levels of cyclins A and B1 correlated with the degree of dysplasia (P
      <.001). However, the cell cycle phase distribution measured with both
      immunostaining and flow cytometry was conserved during all stages of BE,
      dysplasia, and cancer. Hence, the increased proliferation seen in Barrett's
      carcinogenesis is due to abnormal cell cycle entry or exit, rather than a primary
      abnormality within the cell cycle.

PMID- 15720802
TI  - Stability and heterogeneity of expression profiles in lung cancer specimens
      harvested following surgical resection.
AB  - One of the major concerns in microarray profiling studies of clinical samples is
      the effect of tissue sampling and RNA extraction on data. We analyzed gene
      expression in lung cancer specimens that were serially harvested from tumor mass
      and snap-frozen at several intervals up to 120 minutes after surgical resection.
      Global gene expression was profiled on cDNA microarrays, and selected stress and
      hypoxia-activated genes were evaluated using real-time reverse transcription
      polymerase chain reaction (RT-PCR). Remarkably, similar gene expression profiles
      were obtained for the majority of samples regardless of the time that had elapsed
      between resection and freezing. Real-time RT-PCR studies showed significant
      heterogeneity in the expression levels of stress and hypoxia-activated genes in
      samples obtained from different areas of a tumor specimen at one time point after
      resection. The variations between multiple samplings were significantly greater
      than those of elapsed time between sampling/freezing. Overall samples snap-frozen
      within 30 to 60 minutes of surgical resection are acceptable for gene expression
      studies, thus making sampling and snap-freezing of tumor samples in a routine
      surgical pathology laboratory setting feasible. However, sampling and pooling
      from multiple sites of each tumor may be necessary for expression profiling
      studies to overcome the molecular heterogeneity present in tumor specimens.

PMID- 15720803
TI  - Early neoplastic progression is complement independent.
AB  - Infiltration of leukocytes into premalignant tissue is a common feature of many
      epithelial neoplasms and is thought to contribute to cancer development. However,
      the molecular and cellular regulatory mechanisms underlying activation of innate
      host responses to enhanced neoplastic cell proliferation are largely unknown.
      Considering the importance of the complement system in regulating inflammation
      during acute pathologic tissue remodeling, we examined the functional
      significance of complement component 3 (C3) as a regulator of inflammatory cell
      infiltration and activation during malignant progression by using a transgenic
      mouse model of multistage epithelial carcinogenesis, e.g., HPV16 mice. Whereas
      abundant deposition of C3 is a characteristic feature of premalignant
      hyperplasias and dysplasias coincident with leukocyte infiltration in neoplastic
      tissue, genetic elimination of C3 neither affects inflammatory cell recruitment
      toward neoplastic skin nor impacts responding pathways downstream of inflammatory
      cell activation, e.g., keratinocyte hyperproliferation or angiogenesis. Taken
      together, these data suggest that complement-independent pathways are critical
      for leukocyte recruitment into neoplastic tissue and leukocyte-mediated
      potentiation of tumorigenesis.

PMID- 15720804
TI  - MMP-10 is overexpressed, proteolytically active, and a potential target for
      therapeutic intervention in human lung carcinomas.
AB  - Matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix
      is a major factor for tumor development and expansion. This study analysed MMP-10
      protein expression and activity in human lung tumors of various grade, stage, and
      type to address the relationship between MMP-10 and tumor characteristics and to
      evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC).
      Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to
      tumor stroma. MMP-10 protein was observed at low levels in normal human lung
      tissues and at significantly higher levels in all types of NSCLC. No correlation
      was observed between MMP-10 protein expression and tumor type, stage, or lymph
      node invasion. To discriminate between active and inactive forms of MMP-10 in
      samples of human NSCLC, we have developed an ex vivo fluorescent assay.
      Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and
      only 2 of 10 specimens of histologically normal lung tissue. No relationship was
      observed between MMP-10 activity levels and clinicopathologic characteristics.
      Our results suggest that MMP-10 is expressed and active at high levels in human
      NSCLC compared to normal lung tissues, and, as such, is a potential target for
      the development of novel therapeutics for lung cancer treatment.

PMID- 15720805
TI  - Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces
      apoptosis in HER2/neu-overexpressing breast cancer cells.
AB  - In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of
      gene expression referred to as RNA interference (RNAi). We exploited RNAi to
      define the role of HER2/neu in the neoplastic proliferation of human breast
      cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer
      cells with short interfering RNA (siRNA) targeted against human HER2/neu and
      analyzed the specific inhibition of HER2/neu expression by Northern and Western
      blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific
      decrease in HER2/neu mRNA and protein levels. Moreover, transfection with
      HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines
      SK-BR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA
      treatment resulted in an antiproliferative and apoptotic response in cells
      overexpressing HER2/neu, but had no influence in cells with almost no expression
      of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu
      function is essential for the proliferation of HER2/neu-overexpressing breast
      cancer cells. Our observations suggest that siRNA targeted against human HER2/neu
      may be valuable tools as antiproliferative agents that display activity against
      neoplastic cells at very low doses.

PMID- 15720806
TI  - Stromal staining for PINCH is an independent prognostic indicator in colorectal
      cancer.
AB  - Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM
      domain adapter protein that functions in the integrin and growth factor signal
      transduction pathway, is upregulated in stroma associated with many common
      cancers. The finding suggested that PINCH may be involved in promoting tumor
      stromal interactions that support tumor progression, and, if so, tumors with
      abundant PINCH stromal staining may have a worse prognosis. To test this
      hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa
      samples and 26 metastases in the lymph nodes were studied by
      immunohistochemistry, and 7 additional colon tumors were studied by Western blot
      analysis and immunofluorescence. The abundance of PINCH protein in stroma
      increased from normal mucosa to primary tumor to metastasis (P <.05), and was
      more intense at the invasive margin than it was in the intratumoral stroma.
      Strong stromal immunostaining for PINCH was shown to predict a worse outcome
      (rate ratio 2.1, 95% CI 1.16-3.37, P=.01), independent of Dukes stage, growth
      pattern, and tumor differentiation. PINCH was detected in fibroblasts,
      myofibroblasts, and a proportion of endothelial cells of the tumor vasculature,
      supporting the involvement of PINCH in promoting tumor-stromal interactions that
      support tumor progression. Interestingly, stromal staining for PINCH was an
      independent prognostic indicator in colorectal cancer.

PMID- 15720807
TI  - Exposure of human lung cancer cells to 8-chloro-adenosine induces G2/M arrest and
      mitotic catastrophe.
AB  - 8-Chloro-adenosine (8-Cl-Ado) is a potent chemotherapeutic agent whose
      cytotoxicity in a variety of tumor cell lines has been widely investigated.
      However, the molecular mechanisms are uncertain. In this study, we found that
      exposure of human lung cancer cell lines A549 (p53-wt) and H1299 (p53-depleted)
      to 8-Cl-Ado induced cell arrest in the G2/M phase, which was accompanied by
      accumulation of binucleated and polymorphonucleated cells resulting from aberrant
      mitosis and failed cytokinesis. Western blotting showed the loss of
      phosphorylated forms of Cdc2 and Cdc25C that allowed progression into mitosis.
      Furthermore, the increase in Ser10-phosphorylated histone H3-positive cells
      revealed by fluorescence-activated cell sorting suggested that the agent-targeted
      cells were able to exit the G2 phase and enter the M phase. Immunocytochemistry
      showed that microtubule and microfilament arrays were changed in exposed cells,
      indicating that the dynamic instability of microtubules and microfilaments was
      lost, which may correlate with mitotic dividing failure. Aberrant mitosis
      resulted in mitotic catastrophe followed by varying degrees of apoptosis,
      depending on the cell lines. Thus, 8-Cl-Ado appears to exert its cytotoxicity
      toward cells in culture by inducing mitotic catastrophe.

PMID- 15720808
TI  - STRAP is a strong predictive marker of adjuvant chemotherapy benefit in
      colorectal cancer.
AB  - BACKGROUND: Molecular predictors for the effectiveness of adjuvant chemotherapy
      in colorectal cancer are of considerable clinical interest. To this aim, we
      analyzed the serine threonine receptor-associated protein (STRAP), an inhibitor
      of TGF-beta signaling, with regard to prognosis and prediction of adjuvant 5-FU
      chemotherapy benefit. METHODS: The gene copy status of STRAP was determined using
      quantitative real-time polymerase chain reaction in 166 colorectal tumor
      biopsies, which had been collected from a randomized multicenter trial of 5
      fluorouracil (5-FU)/mitomycin C (MMC) adjuvant chemotherapy of the Swiss Group
      for Clinical Cancer Research (SAKK). RESULTS: Amplification of STRAP was found in
      22.8% of the tumors. When left without adjuvant chemotherapy, patients bearing
      tumors with a STRAP amplification had a significantly better prognosis (hazard
      ratio for death: 0.26; P=.004). Interestingly, these patients, when receiving
      adjuvant treatment, had a worse survival (hazard ratio for death: 3.48; P=.019)
      than without chemotherapy, whereas patients carrying tumors with diploidy or
      deletion of STRAP benefited from the treatment (hazard ratio for death: 0.44;
      P=.052). This suggests the amplification of STRAP as a strong predictor of an
      unfavorable effect of 5-FU-based adjuvant chemotherapy. CONCLUSION: If confirmed,
      the STRAP gene copy status might provide a parameter to decide about the use of 5
      FU-based adjuvant chemotherapy.

PMID- 15720809
TI  - Overexpression of 12/15-lipoxygenase, an ortholog of human 15-lipoxygenase-1, in
      the prostate tumors of TRAMP mice.
AB  - Changes in the expression and activity of lipid-metabolizing enzymes, including
      the linoleic acid (LA)-metabolizing enzyme 15-lipoxygenase-1 (15-LO-1), may play
      a role in the development and progression of human prostate carcinoma (PCa). We
      reported that human 15-LO-1 (designated as leukocyte type 12-LO or 12/15-LO in
      mouse) is expressed in human prostate and increased in PCa, particularly high
      grade PCa. Genetically engineered mouse (GEM) models of PCa could facilitate the
      study of this gene and its regulation and function in PCa progression. In this
      study, we examine the protein expression and enzyme activity levels of 12/15-LO
      associated with PCa progression in the TRansgenic Adenocarcinoma of Mouse
      Prostate (TRAMP) model of PCa. This GEM model develops prostatic intraepithelial
      neoplasia (PIN), followed by invasive gland-forming PCa and invasive and
      metastatic less differentiated PCa, with neuroendocrine (NE) differentiation (NE
      Ca). In the wild-type and TRAMP prostates, the most prominent LA metabolite was
      13-hydroxyoctadecadienoic acid (13-HODE). Lesser amounts of 12
      hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid (HETE) were made
      from arachidonic acid (AA). In TRAMP prostates, 12/15-LO activity was increased
      compared to wild type at 20, 29, 39, and 49 weeks, as assessed by LA conversion
      to 13-HODE, and by AA conversion to 12/15-HETE, respectively. Immunostaining
      demonstrated that the increased capacity to generate 13-HODE was paralleled by an
      increase in neoplastic epithelial expression of 12/15-LO in PIN and invasive
      carcinomas. In conclusion, although there is a basal 12/15-LO activity in the
      wild-type mouse prostate, there is a marked increase in the expression of 12/15
      LO with TRAMP PCa progression, paralleling our previously reported increased
      expression of the ortholog 15-LO-1 in high-grade human PCa. Thus, 12/15-LO and LA
      metabolism in the TRAMP model shares similarities to human PCa, and may allow to
      confirm a role for LA metabolism and other biologic functions of 15-LO-1 in human
      PCa. In addition, the TRAMP model will serve as a tool for testing the
      suitability of 12/15-LO-and ultimately human 15-LO--as a therapeutic target
      during PCa progression.

PMID- 15720810
TI  - Changes in water mobility measured by diffusion MRI predict response of
      metastatic breast cancer to chemotherapy.
AB  - The goal of oncology is the individualization of patient care to optimize
      therapeutic responses and minimize toxicities. Achieving this will require
      noninvasive, quantifiable, and early markers of tumor response. Preclinical data
      from xenografted tumors using a variety of antitumor therapies have shown that
      magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent
      diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in
      the tumor. This communication tests the hypothesis that changes in water mobility
      will quantitatively presage tumor responses in patients with metastatic liver
      lesions from breast cancer. A total of 13 patients with metastatic breast cancer
      and 60 measurable liver lesions were monitored by diffusion MRI after initiation
      of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11,
      and 39 days following the initiation of therapy for determination of volumes and
      ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11
      days after commencement of therapy, depending on the analytic method. The highest
      concordance was observed in tumor lesions that were less than 8 cm3 in volume at
      presentation. These results suggest that diffusion MRI can be useful to predict
      the response of liver metastases to effective chemotherapy.

PMID- 15720811
TI  - Characteristics of stem cells from human neuroblastoma cell lines and in tumors.
AB  - Cellular heterogeneity is a hallmark of human neuroblastoma tumors and cell
      lines. Within a single neuroblastoma are cells from distinct neural crest
      lineages whose relative abundance is significant for prognosis. We postulate that
      a self-renewing multipotent tumor stem cell, which gives rise to diverse cell
      lineages, is the malignant progenitor of this cancer. To test this hypothesis, we
      have established 22 cloned, phenotypically homogeneous populations of the three
      major cell types from 17 neuroblastoma cell lines. In vitro, malignant
      neuroblastoma stem cells, termed I-type (intermediate type), have distinct
      morphologic, biochemical, differentiative, and tumorigenic properties. I-type
      cells express features of both neuroblastic (N) cells (scant cytoplasm, neuritic
      processes, neurofilaments, pseudoganglia, and granin and neurotransmitter enzyme
      expression) and substrate-adherent (S) cells (extensive cytoplasm and vimentin
      and CD44 expression). Moreover, they show bidirectional differentiation to either
      N or S cells when induced by specific agents. I-type cells are significantly more
      malignant than N- or S-type cells, with four- to five-fold greater plating
      efficiencies in soft agar and six-fold higher tumorigenicity in athymic mice.
      Differences in malignant potential are unrelated to N-myc
      amplification/overexpression or the ability to digest and migrate through the
      extracellular matrix. Immunocytochemical analyses of a small series of tumors
      reveal that frequency of cells coexpressing N and S cell markers correlates with
      poor prognosis. Thus, I-type stem cells may be instrumental in the genesis and
      growth of tumors in the patient. Their unique biology deserves attention and
      further investigation.

PMID- 15720812
TI  - Phosphorylation of both EGFR and ErbB2 is a reliable predictor of prostate cancer
      cell proliferation in response to EGF.
AB  - Despite multiple reports of overexpression in prostate cancer (PC), the reliance
      of PC cells on activated epidermal growth factor receptor (EGFR) and its
      downstream signaling to phosphoinositide 3'-kinase/Akt (PI3K/Akt/PTEN) and/or
      mitogen-activated protein kinase (MAPK/ERK) pathways has not been fully
      elucidated. In this study, we compared the role of EGF-mediated signaling in
      nonmalignant (BPH-1, PNT1A, and PNT1B) and PC cell lines (DU145, PC3, LNCaP, and
      CWR22Rv1). EGF-induced proliferation was observed in all EGFR-expressing PC cells
      except PC3, indicating that EGFR expression does not unequivocally trigger
      proliferation following EGF stimulation. ErbB2 recruitment potentiated EGF
      induced signals and was associated with the most pronounced effects of EGF
      despite low EGFR expression. In this way, the sum of EGFR and ErbB2 receptor
      phosphorylation proved to be a more sensitive indicator of EGF-induced
      proliferation than quantification of the expression of either receptor alone.
      Both Akt and ERK were rapidly phosphorylated in response to EGF, with ERK
      phosphorylation being the weakest in PC3 cells. Extrapolation of these findings
      to clinical PC suggests that assessment of phosphorylated EGFR + ErbB2 together
      could serve as a marker for sensitivity to anti-EGFR-targeted therapies.

PMID- 15720813
TI  - Gene expression profile of glioblastoma multiforme invasive phenotype points to
      new therapeutic targets.
AB  - The invasive phenotype of glioblastoma multiforme (GBM) is a hallmark of
      malignant process, yet molecular mechanisms that dictate this locally invasive
      behavior remain poorly understood. Gene expression profiles of human glioma cells
      were assessed from laser capture-microdissected GBM cells collected from paired
      patient tumor cores and white matter-invading cell populations. Changes in gene
      expression in invading GBM cells were validated by quantitative reverse
      transcription polymerase chain reaction (QRT-PCR) and immunohistochemistry in an
      independent sample set. QRT-PCR confirmed the differential expression in 19 of 21
      genes tested. Immunohistochemical analyses of autotaxin (ATX), ephrin B3, B-cell
      lymphoma-w (BCLW), and protein tyrosine kinase 2 beta showed them to be expressed
      in invasive glioma cells. The known GBM markers, insulin-like growth factor
      binding protein 2 and vimentin, were robustly expressed in the tumor core. A
      glioma invasion tissue microarray confirmed the expression of ATX and BCLW in
      invasive cells of tumors of various grades. GBM phenotypic and genotypic
      heterogeneity is well documented. In this study, we show an additional layer of
      complexity: transcriptional differences between cells of tumor core and invasive
      cells located in the brain parenchyma. Gene products supporting invasion may be
      novel targets for manipulation of brain tumor behavior with consequences on
      treatment outcome.

PMID- 15720814
TI  - Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with
      pancreatic ductal adenocarcinoma and chronic pancreatitis: a meta-analysis.
AB  - Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in
      the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine
      whether the K-ras mutation rate increases parallel to the grade of dysplasia in
      duct lesions, we performed a meta-analysis of the studies published between 1988
      and 2003 that provide information on K-ras mutations in hyperplastic and
      dysplastic duct lesions in the pancreas. The described duct lesions were
      reclassified according to the nomenclature for pancreatic intraepithelial
      neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed.
      In PanIN lesions from pancreata of patients with PDAC, there was a stepwise
      increase in K-ras mutations that correlated with the grade of dysplasia of the
      PanIN lesion. K-ras mutations were found in 36%, 44%, and 87% of PanIN-1a, 1b,
      and 2-3 lesions, respectively (trend statistic P <.001). Mutation-enriched
      polymerase chain reaction (PCR) resulted in higher rates of K-ras mutations in
      PanIN than plain PCR did. The incidence of K-ras mutations in PanIN lesions
      associated with chronic pancreatitis (CP) or normal pancreas was low (around
      10%). In CP, K-ras mutations were only found after a disease duration of 3 years.
      The correlation of the incidence of K-ras mutations with the grade of dysplasia
      in PanIN and the occurrence of these mutations in CP with a duration of more than
      3 years underlines the importance of this genetic change for the development of
      PDAC.

PMID- 15720815
TI  - Grape seed proanthocyanidins induce apoptosis through p53, Bax, and caspase 3
      pathways.
AB  - Grape seed proanthocyanidins (GSP) have been shown to inhibit skin chemical
      carcinogenesis and photocarcinogenesis in mice. The mechanisms responsible for
      the anticarcinogenic effects of GSP are not clearly understood. Here, we report
      that treatment of JB6 C141 cells (a well-developed cell culture model for
      studying tumor promotion in keratinocytes) and p53+/+ fibroblasts with GSP
      resulted in a dose-dependent induction of apoptosis. GSP-induced (20-80 g/ml)
      apoptosis was observed by using immunofluorescence (27-90% apoptosis) and flow
      cytometry (18-87% apoptosis). The induction of apoptosis by GSP was p53-dependent
      because it occurred mainly in cells expressing wild-type p53 (p53+/+; 15-80%) to
      a much greater extent than in p53-deficient cells (p53-/-; 6-20%). GSP-induced
      apoptosis in JB6 C141 cells was associated with increased expression of the tumor
      suppressor protein, p53, and its phosphorylation at Ser15. The antiapoptotic
      proteins, Bcl-2 and Bcl-xl, were downregulated by GSP, whereas the expression of
      the pro-apoptotic protein, Bax, and the levels of cytochrome c release, Apaf-1,
      caspase-9, and cleaved caspase 3 (p19 and p17) were markedly increased in JB6
      C141 cells. The downregulation of Bcl-2 and upregulation of Bax were also
      observed in wild-type p53 (p53+/+) fibroblasts but was not observed in their p53
      deficient counterparts. These data clearly demonstrate that GSP-induced apoptosis
      is p53-dependent and mediated through the Bcl-2, Bax, and caspase 3 pathways.

PMID- 15720816
TI  - Comparative effect of oncolytic adenoviruses with E1A-55 kDa or E1B-55 kDa
      deletions in malignant gliomas.
AB  - Replication-competent oncolytic adenoviruses hold considerable promise for
      treating malignant gliomas. The toxicity of the clinically tested E1B-55 kDa
      mutant virus is negligible; however, its full clinical potential is still being
      evaluated. The purpose of the present study is to compare the antiglioma activity
      in vitro and in vivo between Delta-24, an E1A mutant adenovirus, and RA55, an E1B
      55 kDa mutant adenovirus. We selected human glioma cell lines that were
      tumorigenic in nude mice and express wild-type p53 (U-87 MG, D54 MG) or mutant
      p53 (U-251 MG, U-373 MG) protein. Our studies demonstrated that Delta-24 induced
      a more potent antiglioma effect in vitro than RA55. Moreover, Delta-24 replicated
      markedly more efficiently than RA55 in both wild-type and mutant p53 scenarios.
      Importantly, direct intratumoral injection of Delta-24, but not RA55,
      significantly suppresses tumor growth in intracranial (U-87 MG, U-251 MG) or
      subcutaneous (D54 MG) animal models. Staining for hexon protein detected
      replicating adenoviruses in xenografts infected with Delta-24, but not with RA55.
      Collectively, these data indicate that E1A mutant adenoviruses targeting the Rb
      pathway are more powerful putative agents for antiglioma therapy than E1B mutant
      adenoviruses, and suggest that E1A mutant adenoviruses should be tested in the
      clinical setting for patients with malignant gliomas.

PMID- 15720817
TI  - Host plasminogen activator inhibitor-1 promotes human skin carcinoma progression
      in a stage-dependent manner.
AB  - Angiogenesis and tumor expansion are associated with extracellular matrix
      remodeling and involve various proteases such as the plasminogen
      (Plg)/plasminogen activator (PA) system. Recently, several experimental data have
      implicated the plasminogen activator inhibitor-1 (PAI-1) in tumor angiogenesis in
      murine systems. However, little is known about PAI-1 functions in human skin
      carcinoma progression. By generating immunodeficient mice (in Rag-1-/- or nude
      background) deleted for PAI-1 gene (PAI-1-/-), we have evaluated the impact of
      host PAI-1 deficiency on the tumorigenicity of two malignant human skin
      keratinocyte cell lines HaCaT II-4 and HaCaT A5-RT3 forming low-grade and high
      grade carcinomas, respectively. When using the surface transplantation model,
      angiogenesis and tumor invasion of these two cell lines are strongly reduced in
      PAI-1-deficient mice as compared to the wild-type control animals. After
      subcutaneous injection in PAI-1-/- mice, the tumor incidence is reduced for HaCaT
      II-4 cells, but not for those formed by HaCaT A5-RT3 cells. These data indicate
      that PAI-1 produced by host cells is an important contributor to earlier stages
      of human skin carcinoma progression. It exerts its tumor-promoting effect in a
      tumor stage-dependent manner, but PAI-1 deficiency is not sufficient to prevent
      neoplastic growth of aggressive tumors of the human skin.

PMID- 15720818
TI  - Epigenetic silencing of cellular retinol-binding proteins in nasopharyngeal
      carcinoma.
AB  - Aberrant retinoid signaling in human cancers is extending from the nucleus to the
      cytoplasm. Recently, we have demonstrated frequent epigenetic inactivation of a
      retinoic acid receptor (RAR), RARbeta2, in nasopharyngeal carcinoma (NPC). To
      further explore targets contributing to aberrant retinoid signaling in NPC, the
      expression of cellular retinol-binding proteins (CRBPs), cellular retinoic acid
      binding proteins (CRABPs), RARs, and retinoid X receptors (RXRs) was examined.
      Apart from RARbeta2, transcriptional silencing of two CRBPs, CRBPI and CRBPIV,
      was observed in NPC cell lines and xenografts. Hypermethylation of CRBPI and
      CRBPIV CpG islands was found to be closely correlated with the loss of
      expression. Treatment with the DNA methyltransferase inhibitor, 5-aza-2'
      deoxycytidine, resulted in reexpression of CRBP1 and CRBPIV gene expression in
      NPC cell lines. Both CRBPI and CRBPIV hypermethylations were also observed in
      43/48 (87.8%) and 26/48 (54.2%) primary NPC tumors, respectively. Here, we
      reported for the first time that CRBPIV was transcriptionally inactivated by
      promoter hypermethylation in human cancer. Simultaneous methylation of CRBPI,
      CRBPIV, and RARbeta2 was commonly found in NPC primary tumors. Our findings
      implied that epigenetic disruption of the CRBPs, CRBPI and CRBPIV, is important
      in NPC tumorigenesis and may contribute to the loss of retinoic acid
      responsiveness in cancer.

PMID- 15720820
TI  - CF101, an agonist to the A3 adenosine receptor, enhances the chemotherapeutic
      effect of 5-fluorouracil in a colon carcinoma murine model.
AB  - NF-kappaB and the upstream kinase PKB/Akt are highly expressed in chemoresistance
      tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to
      the A3 adenosine receptor (A3AR), inhibits the development of colon carcinoma
      growth in cell cultures and xenograft murine models. Because CF101 has been shown
      to downregulate PKB/Akt and NF-kappaB protein expression level, we presumed that
      its combination with chemotherapy will enhance the antitumor effect of the
      cytotoxic drug. In this study, we utilized 3-[4,5-Dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) and colony formation assays and a colon
      carcinoma xenograft model. It has been shown that a combined treatment of CF101
      and 5-fluorouracil (5-FU) enhanced the cytotoxic effect of the latter on HCT-116
      human colon carcinoma cell proliferation and tumor growth. Downregulation of
      PKB/Akt, NF-kappaB, and cyclin D1, and upregulation of caspase-3 protein
      expression level were observed in cells and tumor lesions on treatment with a
      combination of CF101 and 5-FU. Moreover, in mice treated with the combined
      therapy, myelotoxicity was prevented as was evidenced by normal white blood cell
      and neutrophil counts. These results show that CF101 potentiates the cytotoxic
      effect of 5-FU, thus preventing drug resistance. The myeloprotective effect of
      CF101 suggests its development as an add-on treatment to 5-FU.

PMID- 15720819
TI  - The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma.
AB  - The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic
      properties; however, its expression and function in esophageal adenocarcinoma
      (EA) remain poorly understood. We aimed to determine the expression and potential
      alterations in Met expression in EA. Met expression was investigated in surgical
      specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using
      immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase
      chain reaction. Met expression, phosphorylation, and the effect of COX-2
      inhibition on expression were examined in EA cell lines. IHC demonstrated intense
      Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast,
      minimal immunostaining was observed in BE without dysplasia or NE specimens. Met
      mRNA and protein levels were increased in three EA cell lines, and Met protein
      was phosphorylated in the absence of serum. Sequence analysis found the kinase
      domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression
      was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2
      inhibition decreased Met expression. Met is consistently overexpressed in EA
      surgical specimens and in three EA cell lines. Met dysregulation occurs early in
      Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as
      a potential biologic therapy for EA is warranted.

PMID- 15720822
TI  - Distinct trans-plasma membrane redox pathways reduce cell-impermeable dyes in
      HeLa cells.
AB  - Trans-plasma membrane electron transport (tPMET) in mammalian cells has been
      demonstrated using artificial cell-impermeable dyes, but the extent to which
      reduction of these dyes involves distinct pathways remains unclear. Here we
      compare the properties of three commonly used dyes, WST-1, FeCN and DCIP. The
      presence of an intermediate electron carrier (mPMS or CoQ(1)) was obligatory for
      WST-1 reduction, whereas FeCN and DCIP were reduced directly. FeCN reduction was,
      however, greatly enhanced by CoQ(1), whereas DCIP was unaffected. Superoxide
      dismutase (SOD) and aminooxyacetate (AOA), a malate/aspartate shuttle inhibitor,
      strongly inhibited WST-1 reduction and reduced DCIP reduction by 40-60%, but
      failed to affect FeCN reduction, indicating involvement of mitochondrial TCA
      cycle-derived NADH and a possible role for superoxide in WST-1 but not FeCN
      reduction. Reduction of all three substrates was similarly inhibited by
      dicoumarol, diphenyleneiodonium and capsaicin. These results demonstrate that WST
      1 FeCN and DCIP are reduced by distinct tPMET pathways.

PMID- 15720823
TI  - Laser capture microdissection/GeneChip analysis of gene expression in glomerular
      cells in diabetic db/db mice.
AB  - Although the gene expression patterns during the development of diabetic
      nephropathy have been studied in both rodent models and humans, only a small
      portion of the mRNAs expressed in the mesangium or in glomerular cells has been
      characterized. In the present study we report larger groups of transcripts
      displaying significant expression modulation in glomerular cells obtained from
      the early phase of diabetic nephropathy. METHODS: We used 12-week-old female
      db/db mice, a rodent model of type 2 diabetes, and their non-diabetic db/m litter
      mates. Glomerular cells were obtained from the kidneys of mice by laser capture
      microdissection. Preparation of cRNA and target hybridization were performed
      according to the Affymetrix GeneChip Eukaryotic Small Sample Target Labeling
      Assay Protocol (Version II). The gene expression profile was determined by the
      mouse Expression Set 430A GeneChip. RESULTS: By comparison between db/m and db/db
      mice, 649 probes that increased in expression with the induction of diabetes and
      340 probes that decreased in diabetic kidneys were identified. Although some of
      these genes have previously been shown to play an important role in diabetic
      nephropathy, the large majority of them have never been demonstrated to be
      regulated during the development of nephropathy. CONCLUSIONS: Although the
      precise involvement of these genes in diabetic nephropathy remains to be
      clarified, the data presented here will aid in the identification of genes that
      play a significant role in this pathological condition.

PMID- 15720824
TI  - Rotenone, a mitochondrial electron transport inhibitor, ameliorates ischemia
      reperfusion-induced intestinal mucosal damage in rats.
AB  - In ischemia-reperfusion (I/R)-induced tissue injury, oxygen radicals can be
      generated by several mechanisms. One of the important sources of oxygen radicals
      is thought to be mitochondrial respiration. The aim of this study was to
      investigate the antioxidative defense effect of the mitochondrial electron
      transport inhibitor, rotenone using the I/R-induced rat intestinal mucosal injury
      model in vivo. Intestinal ischemia was induced for 30 min by applying a small
      clamp to the superior mesenteric artery in rats. Rotenone at a dose of 100 mg/kg
      was given to rats orally 2 h before the ischemia. Intraluminal hemoglobin and
      protein levels, the mucosal content of thiobarbituric acid-reactive substances
      (TBARS), the mucosal myeloperoxidase activity, and the content of inflammatory
      cytokines (CINC-1, TNF-alpha) were all significantly increased from mean basal
      levels after 60 min of reperfusion. These increases after I/R were inhibited by
      treatment with rotenone at a dose of 100 mg/kg. Co-administration with succinate
      (100 mg/kg), a substrate of the mitochondrial electron transport system,
      cancelled significant reduction of intraluminal hemoglobin and mucosal TBARS
      treated with rotenone alone. The results of the present study indicate that
      rotenone inhibited lipid peroxidation and reduced development of the intestinal
      mucosal inflammation induced by I/R in rats. This investigation suggests that
      rotenone has potential as a new therapeutic agent for reperfusion injury.

PMID- 15720825
TI  - Selenium supplementation and ischemia-reperfusion injury in rats.
AB  - Cardiac ischemia--reperfusion injury results in oxidative stress and poor
      physiological recovery. This study examined the amount of lipid and protein
      oxidation during ischemia-reperfusion to assess the degree of oxidative stress.
      Selenium supplementation was used to alter the antioxidant status of rats and the
      recovery of myocardial function post ischemia-reperfusion was investigated. Male
      Wistar rats were fed diets containing 0, 50, and 1000 microg/kg sodium selenite
      for 5 weeks, whilst controls received normal rat food containing 240 microg/kg
      selenium. Langendorff-perfused hearts were subjected to 22.5 min global ischemia
      and 45 min reperfusion, with functional recovery assessed. Heart tissues were
      assayed for the presence of lipid peroxides and protein carbonyls and correlated
      to cardiac recovery. Following ischemia and reperfusion there was a significant
      increase in both protein oxidation and lipid peroxidation. Hearts from selenium
      deficient animals demonstrated higher levels of both protein carbonyls and lipid
      peroxides and were more susceptible to ischemia-reperfusion injury when compared
      to controls (38% versus 47% recovery of rate pressure product (RPP)). Selenium
      supplementation lowered the levels of protein carbonyls and lipid peroxides and
      resulted in improved recovery of cardiac function post ischemia-reperfusion (57%
      recovery of RPP). These data suggest that selenium supplementation may provide an
      effective method for reducing oxidative damage post cardiac ischemia-reperfusion.

PMID- 15720826
TI  - Glutathione reductase is expressed at high levels in pancreatic islet cells.
AB  - Reactive oxygen species are, at least partly, involved in the diabetogenic agent
      induced dysfunction of pancreatic beta-cells because the expression of
      antioxidative and redox proteins is low. We examined the levels of
      antioxidant/redox proteins, peroxiredoxins-1, -4, and -6 and glutathione
      reductase (GR), by immunohistochemistry and found that the expression of GR was
      very high in pancreatic islet cells compared to exocrine cells. When diabetes was
      induced by an intravenous injection of streptozotocin, the pre-administration of
      1,3-bis[2-chloroethyl]-1-nitrosourea, an irreversible inhibitor of GR, made islet
      cells more vulnerable to streptozotocin. These data point to a pivotal role of
      the glutathione redox system in pancreatic islet cells against diabetogenic
      stress.

PMID- 15720827
TI  - Singlet oxygen quenching activity of human serum.
AB  - Singlet oxygen is regarded as contributing to the pathogenesis of various
      diseases including light-induced skin disorders and inflammatory response. In
      this study, the correlation between singlet oxygen quenching activity (SOQA) of
      human serum and blood biochemistry or life-style was evaluated. Healthy
      volunteers were recruited and carried out a measurement of SOQA by using electron
      paramagnetic resonance (EPR) and a questionnaire survey about a smoking. It was
      demonstrated that major quenchers of singlet oxygen in serum are proteins, and
      small molecular anti-oxidants relatively play a minor role. SOQA of whole sera
      showed no correlation with protein concentration, but positively correlated with
      SOQA of small molecular fraction. In vitro studies demonstrated that the decrease
      of sulfhydryl groups by NO or superoxide significantly attenuated SOQA of
      albumin. Together, these results may imply that the underlying oxidative
      condition in each individual influences both small molecular antioxidant states
      and the sulfhydryl content of serum proteins. SOQA of sera from women with a
      smoking history was significantly lower compared to non-smoking women, suggesting
      that the smoking habit impaired the defense mechanism against singlet oxygen.

PMID- 15720828
TI  - Evidence of reactive oxygen species generation in synovial fluid from patients
      with temporomandibular disease by electron spin resonance spectroscopy.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of
      temporomandibular disorders. In the present study, we provide the first evidence
      of ROS generation in the synovial fluid from human temporomandibular disorder
      patients, as shown by electron spin resonance (ESR) and spin trapping. Three
      distinct ESR spectra of DMPO spin adducts were observed in the synovial fluid.
      They corresponded to three free radical species: hydroxyl radical (HO(*)),
      hydrogen radical (H(*)), and carbon-center radical (R(*)). Among them, the 5,5
      dimethyl-1-pyrroline-N-oxide (DMPO)-OH spectrum was the most prominent,
      suggesting that HO(*) was dominantly generated in the synovial fluid from
      temporomandibular disorder patients. Desferrioxamine (DFO), an iron chelator,
      strongly depressed the DMPO-OH signal intensity in the synovial fluid from
      patients with temporomandibular disorders. We successfully demonstrated ROS
      induced oxidative stress in the synovial fluid from temporomandibular disorder
      patients. ROS generation in the temporomandibular joint could lead to
      exacerbation of inflammation and activation of cartilage matrix degrading enzymes
      that proceed to degenerative change of the temporomandibular joint. Thus, iron
      dependent generation of HO( *) might have a crucial role in the pathogenesis of
      temporomandibular disorders.

PMID- 15720829
TI  - Gene expression analysis following hypoxia-reoxygenation in rat gastric
      epithelial cells using a high-density oligonucleotide array.
AB  - Recent investigations have demonstrated that the signaling of hypoxia-re
      oxygenation is a major contributing pathway leading to gastric mucosal injury
      induced by stress, non-steroidal anti-inflammatory drugs, and Helicobacter
      pylori. The aim of the present study was to perform a gene expression analysis on
      the gastric mucosal cellular response to hypoxia-reoxygenation using a high
      density oligonucleotide array. Cells were subjected to hypoxia with 95% N(2) and
      5% CO(2) at 37 degrees C for 2 h. Reoxygenation was initiated by placing the
      cells in an environment of normoxia for 2 h. Total RNA was extracted, and
      differences in gene expression profiles between the normoxia and hypoxia
      reoxygenation groups were investigated using a GeneChip of Rat Toxicology U34
      array (Affymetrix). Hypoxia-reoxygenation up-regulated the stress-related genes
      (heat shock protein-70 [HSP-70], catalase). The enhanced expression of HSP-70 was
      confirmed by Western blot analysis. In conclusion, these results suggest that up
      regulation of the HSP-70 gene after reoxygenation may play a role in maintaining
      cell survival and supporting cell function as a molecular chaperone.

PMID- 15720830
TI  - Possible role of NF-kappaB in Bcl-X(L) protection against hydrogen peroxide
      induced PC12 cell death.
AB  - Bcl-X(L), a mitochondrial membrane protein, blocks apoptosis induced by a wide
      array of death signals. In spite of extensive research, the molecular milieu that
      characterizes the anti-apoptotic function of Bcl-X(L) is complex and not fully
      clarified. In the present work, we have investigated the role of Bcl-X(L) in
      protecting against oxidative death induced by H(2)O(2) in cultured rat
      pheochromocytoma (PC12) cells. PC12 cells exposed to H(2)O(2) underwent apoptotic
      cell death as determined by internucleosomal DNA fragmentation and an increased
      pro-apoptotic Bax to anti-apoptotic Bcl-X(L) ratio. Moreover, stable transfection
      with the bcl-X(L) gene rescued PC12 cells from apoptotic death caused by
      H(2)O(2). PC12 cells overexpressing bcl-X(L) exhibited relatively high
      constitutive transcriptional as well as DNA binding activities of NF-kappaB,
      compared with the vector-transfected control cells. Addition of NF-kappaB
      inhibitors, such as parthenolide and N-tosyl-L-phenylalanine chloromethyl ketone,
      to the media aggravated H(2)O(2)-induced oxidative cell death. PC12 cells
      transfected with bcl-X(L) exhibited higher levels of the heme oxygenase-1, which
      may confer these cells protection against oxidative stress. These results suggest
      that the redox-sensitive transcription factor NF-kappaB may play a role in bcl
      X(L)-mediated protection against oxidative cell death.

PMID- 15720831
TI  - Cadmium-induced synthesis of HSP70 and a role of glutathione in Euglena gracilis.
AB  - The effect of cadmium-induced oxidative stress, with or without glutathione
      supplementation, was investigated in the single cell eukaryotic phytoflagellate,
      Euglena gracilis strains Z and its achlorophyllous mutant SMZ as experimental
      models. Both these strains actively synthesize thiols to prevent or resist
      cadmium toxicity. The content of glutathione, as a representative antioxidant,
      was also examined in both strains. Exposure to cadmium induced heat-shock protein
      70 (HSP70) synthesis in both strains of E. gracilis. Glutathione supplementation
      also induced HSP70. Overall, these results indicate that glutathione was closely
      linked to the induction of stress-related proteins. The sensitivity to cadmium
      stress was higher in strain Z than SMZ. The results suggest that chloroplasts may
      have a role in the regulation of HSP70 expression. The relationship between HSP70
      and GSH levels is still far from understood, and further research may shed light
      upon their up-regulation in the presence of Cd.

PMID- 15720832
TI  - The inhibitory effect of alacepril, an angiotensin-converting enzyme inhibitor,
      on endothelial inflammatory response induced by oxysterol and TNF-alpha.
AB  - The objectives were to determine the effects of alacepril, an angiotensin
      converting enzyme inhibitor, on the expression of adhesion molecules and monocyte
      adherence to endothelial cells induced by 7-ketocholesterol (7-KC) and tumor
      necrosis factor (TNF)-alpha. We used human aortic endothelial cells (HAECs) and
      U937 monocytic cells. Surface expression and mRNA levels of intercellular
      adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were
      determined by EIA and RT-PCR. Adherence of U937 to HAECs was assessed by adhesion
      assay. Incubation of HAEC with 7-KC increased the surface expression of protein
      and mRNA levels of ICAM-1 and VCAM-1 on HAECs and the production of reactive
      oxygen species (ROS) in HAECs. Pretreatment with alacepril reduced the enhanced
      expression of these molecules in a dose-dependent manner. The inhibitory effect
      of alacepril against 7-KC or TNF-alpha-induced CAMs expression was stronger than
      that of captopril or enalapril. Alacepril inhibited the production of ROS in
      HAECs stimulated by 7-KC or TNF-alpha. These results suggest that alacepril works
      as anti-atherogenic agent through inhibiting endothelial-dependent adhesive
      interactions with monocytes induced by 7-KC and TNF-alpha.

PMID- 15720833
TI  - Continuous treatment with organic nitrate affects hepatic cytochrome P450.
AB  - We previously reported that cytochrome P450 (P450) is a key enzyme of organic
      nitrate biotransformation and that P450 levels of the heart and its vessels
      markedly decreased at the development of nitrate tolerance. Escape from tolerance
      of organic nitrate by induction of cytochrome P450. Most organic nitrates,
      including nitroglycerin (NTG), are metabolized in the liver, where nitric oxide
      (NO) is concomitantly produced from the organic nitrates. Therefore, organic
      nitrate administration may also affect hepatic P450 levels, since the liver is
      the major organ of P450-related metabolism. Male Wistar rats were intravenously
      administrated NTG or isosorbide dinitrate (ISDN) for 24-96 h. Hepatic P450 was
      drastically decreased after 48 h or 72 h of continuous NTG or ISDN infusion, when
      nitrate tolerance was observed, but it recovered 48 h after cessation of the drug
      administration. hemeoxygenase-1 (HO-1) was induced within 24 h of continuous NTG
      infusion, but it returned to normal levels 48 h after cessation of the NTG. The
      administration of sodium nitroprusside, an agent to which the animals showed no
      tolerance, did not induce HO-1 or P450 depletion as judged by SDS-PAGE in
      combination with Western-blotting. These results suggest that P450-dependent drug
      metabolism may be drastically affected after continuous organic nitrate
      administration.

PMID- 15720835
TI  - 7-Ketocholesterol enhances the expression of adhesion molecules on human aortic
      endothelial cells by increasing the production of reactive oxygen species.
AB  - The aim of the present study was to assess the expression of intracellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1),
      monocytic adhesion of human aortic endothelial cells (HAECs), and the production
      of intracellular reactive oxygen species (ROS), when HAECs were stimulated by 7
      ketocholesterol. 7-ketocholesterol enhances surface expression of ICAM-1 and VCAM
      1 as determined by EIA, induces their mRNA expression by RT-PCR, and stimulates
      adhesiveness of HAECs to U937 monocytic cells. We confirmed up-regulation of ROS
      production of HAECs treated with 7-ketocholesterol. Although the surface
      expression of ICAM-1 and VCAM-1 on HAECs treated with 7-ketocholesterol increased
      in a time-dependent manner, alpha-tocopherol inhibited this increase of the
      surface expression of ICAM-1 and VCAM-1. In the monocytic adhesion assay,
      adhesion of U937 to HAECs treated with 7-ketocholesterol was enhanced, but
      monoclonal anti-ICAM-1 and VCAM-1 antibodies reduced the endothelial
      adhesiveness. In conclusion, this study suggests that the endothelial
      adhesiveness to monocytic cells that was increased by 7-ketocholesterol was
      associated with enhanced expression of ICAM-1 and VCAM-1 mediated by ROS
      production.

PMID- 15720834
TI  - Hypoxia-reoxygenation enhances interleukin-8 production from U937 human monocytic
      cells.
AB  - Hypoxia--reoxygenation (H/R) occurs in both inflammatory spots and tumor tissues,
      sites in which damage is amplified either acutely or chronically through the
      infiltration of inflammatory cells. Interleukin-8 (IL-8) is a cytokine with
      chemotactic and angiogenic properties. This study was designed to investigate the
      effects of H/R on IL-8 production in the U937 human monocytic cell line. Two
      hours of hypoxia followed by 4 h of reoxygenation induced a significant increase
      in IL-8 protein production and IL-8 mRNA expression in U937 cells. Pretreatment
      with proteasome inhibitor (PSI), a peptide aldehyde known to inhibit the
      chymotrypsin-like activity of the 26S proteasome specifically, suppressed IL-8
      protein production and IL-8 mRNA expression induced by H/R. The production of IL
      8 protein induced by H/R was decreased by pioglitazone and 15-deoxy-Delta(12,14)
      PGJ(2) (15d-PGJ(2)), which have been identified as peroxisome proliferator
      activated receptorgamma (PPAR-gamma) ligands. Moreover, transfection of U937
      cells with a dominant negative IkappaBalphaexpression vector (IkappaBalphaM)
      decreased IL-8 protein production induced by H/R. These results suggest that NF
      kappaB and PPAR-gamma regulate H/R-stimulated IL-8 production in U937 cells.

PMID- 15720836
TI  - A PPAR-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J(2), inhibited gastric
      mucosal injury induced by ischemia-reperfusion in rats.
AB  - INTRODUCTION: Recent studies have demonstrated the anti-inflammatory action of 15
      deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)), a derivative of the PGD(2)
      metabolic pathway. Acute inflammation, including neutrophil activation, plays a
      critical role in the pathogenesis of ischemia-reperfusion (I/R). The aim of the
      present study was to determine the effect of 15d-PGJ(2) on I/R-induced gastric
      mucosal injury in rats. METHODS: Gastric mucosal damage was induced in male
      Wistar rats by clamping the celiac artery for 30 min followed by reperfusion. 15d
      PGJ(2) (0.01-1.0 mg/kg) was given to the rats intraperitoneally 1 h before the
      vascular clamping. The area of gastric mucosal erosions (erosion index) was
      measured. Thiobarbituric acid reactive substances (TBARS) and tissue-associated
      myeloperoxidase (MPO) activity were measured in the gastric mucosa as indices of
      lipid peroxidation and neutrophil infiltration. The expression of tumor necrosis
      factor-alpha (TNF-alpha) in gastric mucosa was measured by ELISA. In addition, to
      elucidate whether the protective effects of 15d-PGJ(2) are related to the
      activation of the PPAR-gamma receptor, we also investigated the effects of a PPAR
      gamma antagonist, GW9662. RESULTS: After 60 min of reperfusion, the area of
      gastric erosion index had significantly increased from the mean basal levels. The
      increase in the erosion index was significantly inhibited by pretreatment with
      15d-PGJ(2) in a dose-dependent manner. On the other hand, GW9662 reversed the
      protective effect of 15d-PGJ(2). The concentration of TBARS and MPO activity in
      the gastric mucosa were both significantly increased after I/R, and pretreatment
      with 15d-PGJ(2) significantly reduced these increases. The TNF-alpha content was
      significantly higher in the I/R group than in the sham-operated group. However,
      the increase in TNF-alpha was significantly inhibited by pretreatment with 15d
      PGJ(2). CONCLUSIONS: 15d-PGJ(2) significantly inhibited the severity of acute
      gastric mucosal injury induced by I/R in rats through PPAR-gamma-dependent
      mechanisms. This effect may be due, in part, to a reduction in the infiltration
      of neutrophils into the gastric mucosa, possibly via the inhibition of
      inflammatory cytokine.

PMID- 15720838
TI  - 'It takes two': men and contraception.

PMID- 15720837
TI  - Regulation of vascular tone by S-nitroso-myoglobin.
AB  - Myoglobin (Mb) is a haem protein present in skeletal, cardiac and smooth muscle
      where it facilitates the transfer of O(2) from the extracellular matrix to the
      cell cytosol in a cycle termed 'facilitated O(2)-diffusion'. In addition, we
      showed recently that recombinant human Mb binds endothelium-derived relaxant
      factor - nitric oxide ((.-)NO) - via formation of both nitrosyl-haem iron and S
      nitroso-myoglobin (S-NO-Mb). S-NO-Mb represents a novel form of endothelium
      derived relaxant factor (EDRF) that may be important in maintaining optimal (.
      )NO concentrations in the human vasculature. In this study we aim to show that:
      (i) S-nitrosation of oxygenated ferrous myoglobin (oxyMb) can compete with the
      rapid oxidation of (.-)NO by oxyMb; and (ii) S-NO-Mb retains characteristics of
      physiological EDRF.

PMID- 15720839
TI  - Debating late abortion: time to tell the truth.

PMID- 15720840
TI  - Medical termination of pregnancy in the early first trimester.
AB  - Surgical abortion using vacuum aspiration or dilatation and curettage has been
      the method of choice for termination of pregnancy up to 63 days' gestation since
      the 1960s. Over the last three decades many studies have explored the use of
      medical methods for inducing abortion at these gestations. Earlier regimens
      assessed the systemic and intrauterine injection of prostaglandins. This was
      followed in the 1980s by the introduction of the antiprogesterone, mifepristone.
      Since its introduction, the uptake of medical abortion has been steadily
      increasing in countries where it has been available for routine use. Most current
      clinical protocols require the use of prostaglandins in combination with anti
      progesterones or antimetabolites. The safety, efficacy and acceptability of the
      medical regimen are now well established at all gestations of pregnancy.
      Provision of medical abortion increases the choice available to women, in
      particular those wishing to avoid surgery.

PMID- 15720841
TI  - Deprivation and variations in teenage conceptions and abortions in England.
AB  - There are substantial variations between local authorities in the conception rate
      of teenagers and the proportion of these that end in abortion. This study builds
      two deprivation models that explain part of the variation in conceptions and
      abortions. It then identifies outliers, local authorities with teenage conception
      and abortion rates that are above or below those predicted by the model. It is
      suggested that the local authorities with lower than expected conceptions are the
      ones to look to when seeking to discover how to prevent teenage conceptions and
      those with higher than expected abortion rates may have abortion services that
      are more accessible. In general, spatial comparisons of conceptions and abortion
      should take into account variations in deprivation.

PMID- 15720842
TI  - Improving induced abortion care in Scotland: enablers and constraints.
AB  - BACKGROUND: Induced abortion is the most common gynaecological procedure in
      Scotland. Despite several recent initiatives to improve the quality of abortion
      care, inappropriate variations in care remain. OBJECTIVE: To identify and explore
      factors that enable or constrain the provision of high-quality induced abortion
      care in Scotland. METHODS: Interviews with a range of key informants with
      differing perspectives and levels of involvement in abortion care. The interview
      framework identified factors related to recommendations, targeted individuals, or
      the organisation and wider environment that enable or inhibit evidence-based
      practice. RESULTS: Induced abortion care in Scotland is generally perceived to be
      of good quality but the need for further action to tackle important inappropriate
      variations in care is recognised. Some aspects of care can be improved by
      tackling individual-level barriers and providing better evidence to support
      change. Some individual-level barriers (e.g.attitudes) are less amenable to
      change than others (e.g.knowledge). However, major barriers to quality
      improvement are rooted in organisational and social culture. CONCLUSION: Tackling
      variations in abortion care requires a multilevel approach targeting both
      individual factors and organisational culture.

PMID- 15720843
TI  - Documentation of preoperative counselling for female sterilisation: a complete
      audit cycle.
AB  - BACKGROUND: Female sterilisation is a commonly performed gynaecological procedure
      that attracts a disproportionate number of complaints and litigation.
      Documentation of the key counselling issues provides an important record of the
      information given to the woman prior to undergoing sterilisation. METHODS:
      Auditable standards were obtained from published guidelines. After the initial
      audit of 100 cases a proforma was introduced in an effort to improve
      documentation. A re-audit of 50 cases was undertaken to ascertain compliance of
      documentation following the introduction of the proforma. RESULTS: The proforma
      was used in 62% of cases and in all such cases documentation was 100% compliant
      with the auditable standards. Overall, documentation of standards pre- and post
      proforma, respectively, was as follows (all the figures quoted are percentage
      values, with the range given in parentheses): 33 (24-43) vs 68 (53-80) for long
      term alternatives, 94 (87-98) vs 78 (62-87) for irreversibility, 96 (90-99) vs 78
      (64-88) for failure rate, 48 (38-58) vs 66 (51-79) for ectopic pregnancy risk if
      sterilisation fails, 39 (29-49) vs 66 (51-79) for the intended method, 67 (57-76)
      vs 66 (51-79) for operative risks and 37 (28-47) vs 64 (49-77) for continuing
      current contraception until sterilisation performed. CONCLUSIONS: Documentation
      of preoperative counselling for female sterilisation is often incomplete and does
      not comply with published recommendations. The introduction of a proforma
      resulted in a mixture of both improvement and deterioration of documentation.
      When the proforma was used, compliance with recommendations was 100%.

PMID- 15720844
TI  - A comparative study of clinical management strategies for vaginal discharge in
      family planning and genitourinary medicine settings.
AB  - OBJECTIVE: To compare strategies for management of women with vaginal discharge
      in genitourinary medicine (GUM) and family planning (FP) settings. METHODS: The
      setting was a centre housing both FP and GUM departments within a primary care
      trust in Scotland. The study participants were 200 women presenting with vaginal
      discharge. A randomised, controlled, crossover design was employed. Strategies
      typical of FP and GUM were performed on every participant in a randomised
      sequence. Day 1 diagnoses were made by the FP strategy (history and examination)
      and the GUM strategy (nearpatient microscopy added). Day 7 results were obtained
      from final analysis of all specimens. Days 1 and 7 results were compared with the
      reference standard provided by all the test results. The main outcome measures
      were incorrect diagnoses on Days 1 and 7. RESULTS: On Day 1 the FP strategy
      resulted in significantly more incorrect diagnoses than the GUM strategy when
      compared with the reference standard (73 vs 32; p <0.001). On Day 7 the GUM
      strategy resulted in significantly more incorrect diagnoses than the FP strategy
      when compared with the reference standard (32 vs 17; p = 0.019). CONCLUSIONS:
      Vaginal discharge can be managed effectively in community settings such as FP and
      primary care. The addition of near-patient microscopy produces a more accurate
      immediate diagnosis. The addition of a high vaginal swab for culture produces a
      more accurate final diagnosis. The costs of on-site microscopy must be
      considered.

PMID- 15720846
TI  - Concerning women: questionnaire survey of consultations, embarrassment, and views
      on confidentiality in general practice among women in their teens, thirties and
      fifties.
AB  - BACKGROUND: Concern exists that women, and in particular teenagers, do not
      consult in general practice, particularly for contraception because of
      embarrassment and concern over confidentiality. The aim of this study was to
      compare reported consultation rates, embarrassment when consulting, and views on
      confidentiality of women in three age groups. METHODS: A postal questionnaire was
      used to survey women aged 16-19, 36-39 and 56-59 years attending a semi-rural
      practice in East Devon, UK in December 1999. RESULTS: Response rates of 57%
      (teenagers), 79% (women in their thirties) and 89% (women in their fifties) were
      achieved. In each group over half the respondents had seen a general practitioner
      (GP) in the previous 3 months. Embarrassment at attending a GP decreased from 38%
      of teenagers to only 16% of women in their fifties. There was a similar pattern
      with 78% of teens and 42% of women in their fifties preferring to see a woman
      doctor for a women's problem and 31% of teens and 18% of women in their fifties
      expressing a preference for a woman doctor for any problem. Some 97% of women in
      their thirties and fifties thought a consultation with a GP would be confidential
      compared with 88% of the teenagers. Only 9% of the teenage group thought the GP
      might tell their parents about the consultation. CONCLUSIONS: This study found
      that teenagers were just as likely as older women to have seen a GP in the
      preceding 3 months. Embarrassment at attending decreased with age, as did the
      preference to see a female doctor for both women's and any problems. The majority
      of women in each age group believed a consultation with a GP, or practice nurse,
      was confidential.

PMID- 15720847
TI  - Female sterilisation in rural Bihar: what are the acceptor characteristics?
AB  - OBJECTIVE: The National Population Policy aims to expand voluntary and informed
      use of contraceptive services. This paper examines the determinants of use of
      female sterilisation versus other contraceptive methods in rural Bihar, one of
      the most socially and economically deprived states in India. METHODS: Data for
      1378 ever-married women aged 15-49 years in rural Bihar, who are currently using
      contraception, were abstracted from the Second National Family Health Survey. A
      logistic regression model was developed to understand the determinants of use of
      female sterilisation versus other contraceptive methods. RESULTS: Maternal age,
      the number of living sons, religion, scheduled caste/tribe/backward class status,
      exposure to mass media and household standard of living are statistically
      significant determinants of the choice between sterilisation and other
      contraceptive methods. CONCLUSION: The study underscores the need to
      significantly broaden the contraceptive choice for women in rural Bihar.

PMID- 15720848
TI  - Potential impact of oral contraceptive choice on myocardial infarction mortality
      and deep vein thrombosis.
AB  - OBJECTIVES: To summarise the epidemiological evidence on the relationship between
      second- (OC2) and third-generation (OC3) oral contraceptives (OC) and the
      mortality associated with deep vein thrombosis (DVT) and myocardial infarction
      (MI), and to extrapolate and balance the evidence for these risks to the
      population of French OC users. METHODS: All studies published on the risk of MI
      during OC2 and OC3 use were analysed. For DVT the Committee for Proprietary
      Medicinal Products public assessment report published in 2001 and more recent
      studies published on this topic were used. The estimates of odds ratios (OR) for
      risk of death from DVT or MI were extracted from the published manuscripts. ORs
      were used to calculate the aetiological fraction of risk for death from DVT and
      MI in the population; the relative impact of OC3 compared to OC2 use was
      expressed as an excess risk of death overall and by age group for French women.
      RESULTS: Compared with OC2, the use of OC3 would prevent a maximum of 24 deaths
      from MI per year and induce a maximum of 16 deaths. Conversely, OC3 would induce
      282-940 excess cases of DVT per year, resulting in 28-94 pulmonary embolisms and
      3-19 deaths in the 4.7 million French OC users. CONCLUSION: Balancing the
      evidence, it is difficult to conclude that the overall cardiovascular risk is
      significantly lower for either of the two OC schemes.

PMID- 15720849
TI  - The analysis of qualitative research data in family planning and reproductive
      health care.

PMID- 15720850
TI  - Evaluating individual performance for clinical governance.

PMID- 15720851
TI  - Developing the role of the specialist nurse in contraception and sexual health
      services.

PMID- 15720852
TI  - FFPRHC Guidance (January 2005) contraception for women aged over 40 years.

PMID- 15720854
TI  - The members' enquiry service: frequently asked questions. For women who are using
      liver enzyme-inducing drugs, what dose of POEC is advised?

PMID- 15720856
TI  - Treatment of pelvic endometriosis with etonogestrel subdermal implant (Implanon).
AB  - BACKGROUND: Endometriosis is one of the commonest benign gynaecological disorders
      and has a peak incidence between 30 and 45 years of age. Treatment options are
      medical or surgical, depending on the location and extent of the disease and the
      woman's childbearing aspirations or need for contraception. Over the past five
      decades several formulations of progestogen have been used to treat
      endometriosis. METHODS: Our study was not planned research but a series of case
      studies of women with severe symptoms of endometriosis treated in an innovative
      way with a new long-acting progestogen contraceptive system (etonogestrel
      subdermal implant) which could reasonably have been expected to have a favourable
      effect on their disease and its symptoms. RESULTS: Five women with severe pelvic
      endometriosis were treated. Two of them were nulliparous and wished to become
      pregnant in due course; the other three had completed their childbearing and were
      contemplating hysterectomy. One of the five women had relief of pelvic pain but
      requested removal of the implant after 3 months because of side effects; the
      other four remained very satisfied with their treatment for the symptoms of
      pelvic endometriosis. Two of the four very satisfied women have had their implant
      replaced and the other two are expected to have their implant replaced when
      necessary. CONCLUSION: Etonogestrel subdermal implants are an additional
      treatment option in women with symptoms related to pelvic endometriosis.

PMID- 15720859
TI  - Migration of implanon: two case reports.
AB  - These two case reports describe migration of Implanon (the single-rod
      contraceptive implant). A review of the literature revealed true migration of
      Implanon to be rare. A change of practice locally is described.

PMID- 15720860
TI  - Pelvic actinomycosis: still a cause for concern.
AB  - Three cases of pelvic actinomycosis, which presented over a short period of time,
      are described. In all three cases the diagnosis was only considered following
      laparotomy, although there were characteristic diagnostic clues at presentation.
      In two cases imaging of the pelvis by ultrasound and computed tomography was
      unhelpful in distinguishing the condition from pelvic neoplasia.

PMID- 15720861
TI  - Communication and termination: whose choice?

PMID- 15720862
TI  - 'Teen mags': helpful or harmful?

PMID- 15720863
TI  - "You cannot be serious".

PMID- 15720865
TI  - Opportunistic screening for chlamydia.

PMID- 15720866
TI  - Drospirenone and PCOS.

PMID- 15720867
TI  - Confidentiality and patient care.

PMID- 15720869
TI  - HPV vaccines.

PMID- 15720871
TI  - Sexual health delivery in general practice.

PMID- 15720875
TI  - Visual inspection with acetic acid for cervical cancer screening outside of low
      resource settings.
AB  - OBJECTIVES: To assess visual inspection with acetic acid (VIA) as a screening
      tool for use in a well-equipped health center in Peru, to evaluate VIA as an
      alternative or adjunct to the Papanicolaou (Pap) smear, and to determine if VIA
      can play a role in settings other than low-resource ones. METHODS: This was a
      prospective study of 1 921 asymptomatic women living in Lima, Peru, carried out
      in 1999 and 2000. The study was performed at a cancer center equipped with the
      latest-generation technology and highly trained oncologists. The women underwent
      a complete clinical evaluation, including a Pap smear and VIA. Participants with
      any positive test were referred for colposcopy and biopsy. RESULTS: More women
      tested positive by VIA than on the Pap smear (6.9% vs. 4.2%; P = 0.0001). There
      were 35 women with histologic cervical intraepithelial neoplasia grade 1 (CIN 1);
      of these, 15 were detected by Pap and 20 by VIA (P = 0.4). A diagnosis of CIN 2
      or 3 (CIN 2-3) was confirmed in a total of 13 cases; Pap detected 5 of the cases
      and VIA 11 of the cases (P = 0.06). The positive predictive value for detection
      of CIN 2+ was 8.3% for VIA and 6.3% for Pap (P = 0.5). Most importantly, while
      only 2.3% of patients with a positive VIA were lost to follow-up before
      colposcopy, that was true for 26.3% of the women with a positive Pap smear (P <
      0.0001). CONCLUSIONS: VIA is useful for detection of precursor lesions of
      cervical cancer not only in low-resource settings but also in well-equipped
      health centers and cancer centers. In these non-low-resource settings, VIA has a
      positive predictive value comparable to the conventional Pap smear, but it is
      more likely to achieve earlier diagnosis, follow-up, and treatment than cytology
      based screening.

PMID- 15720876
TI  - [Acute diarrheal disease: a public health challenge in Colombia].
AB  - OBJECTIVES: To establish the relationship between rotavirus infection and
      dehydration from diarrhea in Colombian children under 5 years of age, and to
      identify risk factors for diarrhea with dehydration. METHODS: A case-control
      study was performed in an urban hospital in Bogota, Colombia, between April 2000
      and February 2001. The sample was composed of 290 children of both sexes under 5
      years of age; of these children, 145 of them were hospitalized for acute
      diarrheal disease (ADD) with dehydration (cases), and 145 had a diagnosis of ADD
      but no signs of dehydration (controls). All children underwent a complete
      physical examination. Mothers responded to a questionnaire containing items on
      demographic and socioeconomic variables, as well as on knowledge, attitudes, and
      practices with regard to hygiene, and on access to health services. RESULTS: An
      association was detected between diarrhea with dehydration and the presence of
      rotavirus in fecal samples (odds ratio [OR] = 3.46; 95% confidence interval [95%
      CI]: 1.71 to 7.00), birth weight < 2 600 g (OR = 7.79; 95% CI: 3.47 to 18.01),
      and breastfeeding for less than 3 months (OR = 3.17; 95% CI: 1.66 to 6.13). The
      risk of having dehydration was associated with low socioeconomic status, poor
      hygienic practices among the child's family members, and mother's low educational
      level. CONCLUSIONS: The ineffectiveness of health promotion and disease
      prevention activities in a population with easy access to health services set the
      stage for the appearance of cases of diarrhea with dehydration. Rotavirus
      infection plays an important role in the severity of ADD among Colombian
      children.

PMID- 15720877
TI  - [Equity and access to health care for pregnant women in Campinas (SP), Brazil].
AB  - OBJECTIVE: To compare the health care received during pregnancy, delivery, and
      the puerperium by women belonging to two different per capita family income
      strata: less than 1 minimum wage, and 1 or more minimum wages. METHOD: This is a
      cross-sectional observational study that was carried out with a random sample of
      248 female residents of the city of Campinas, in the state of Sao Paulo, Brasil,
      who had given birth between April 2001 and March 2002. Sociodemographic data, as
      well as information concerning maternal morbidity and health care during
      pregnancy, delivery, and the puerperium, were obtained through home interviews.
      The Kessner index, the Adequacy of Prenatal Care Utilization index, and an index
      proposed by the authors based on the recommendations of the Brazilian Department
      of Health were used to assess the adequacy of prenatal care. The minimum wage in
      Brazil at the time of the study was 180 reais (approximately 71.4 USD). RESULTS:
      The lower income group included a larger proportion of women with low schooling,
      as well as adolescents, black women, and single women. Prenatal care was provided
      by the public Unified Health System to 73.7% of the women in the lower income
      group, versus 33.3% in the higher income group. The women in the lower income
      group started attending prenatal care later and had fewer visits in all than
      higher-income women. However, some health care quality indicators, such as
      performance of routine laboratory tests and anti-HIV antibody testing, the
      proportion of cesarean sections, and the frequency of infant rooming-in, showed
      more favorable figures in the lower income group. Both groups received comparable
      counseling and had similar rates of clinical testing, post-delivery tubal
      sterilization, low birthweight children, and premature delivery. Although a
      significantly higher number of women in the higher income group received optimal
      prenatal care, the percentage of cases of inadequate care in the lower-income
      group was still relatively low. The frequency of health problems during pregnancy
      did not differ significantly between groups, except for anemia and vaginal
      hemorrhage, which were more frequent among women in the lower-income group (P <
      0.001 and P = 0.033, respectively). CONCLUSIONS: Despite marked socio-demographic
      differences between women in the two income categories, resulting in different
      living conditions, there were no significant differences between groups in terms
      of health problems during pregnancy or the quality of the prenatal care received.
      These results suggest that the organization of public health services in Campinas
      has succeeded in promoting equity in health care, at least to a certain extent.

PMID- 15720878
TI  - HIV infection in mobile populations: the case of Mexican migrants to the United
      States.
AB  - OBJECTIVE: Previous studies have indicated varying rates of HIV infection among
      labor migrants to the United States of America. Most of these studies have been
      conducted with convenience samples of farmworkers, thus presenting limited
      external validity. This study sought to estimate the prevalence of HIV infection
      and risk factors among Mexican migrants traveling through the border region of
      Tijuana, Baja California, Mexico, and San Diego, California, United States. This
      region handles 37% of the migrant flow between Mexico and the United States and
      represents the natural port of entry for Mexican migrants to California. METHODS:
      From April to December 2002 a probability survey was conducted at key migrant
      crossing points in Tijuana. Mexican migrants, including ones with a history of
      illegal migration to the United States, completed an interview on HIV risk
      factors (n = 1 429) and an oral HIV antibody test (n = 1,041). RESULTS: Despite
      reporting risk factors for HIV infection, none of the migrants tested positive
      for HIV. CONCLUSIONS: Our findings contrast with previous estimates of HIV among
      labor migrants in the United States that were based on nonprobability samples.
      Our findings also underline the need for early HIV prevention interventions
      targeting this population of Mexican migrants.

PMID- 15720880
TI  - [Epidemiology and genetics: a strategic alliance in the new millennium?].

PMID- 15720879
TI  - [Liver changes in workers at an oil refinery and in a reference population in the
      state of Bahia, Brazil].
AB  - OBJECTIVE: To determine the prevalence of liver changes in workers at an oil
      refinery located in the state of Bahia, Brazil, as compared to a reference
      population with no occupational exposure to chemical products, and to describe
      the factors associated with the observed differences in prevalence. METHODS: We
      studied workers at the refinery and at the company's central management office
      located in the city of Salvador, which is the state capital. Blood samples of 692
      refinery workers and 377 workers from the reference population were analyzed.
      Cases were defined as individuals presenting high serum levels of both
      gammaglutamyltransferase (GGT) and alanine aminotransferase (ALT) (GGT > 50 U/L
      for males and > 32 U/L for females; ALT > 50 U/L). Data were collected on age,
      sex, weight, height, years working for the company, use of alcohol, smoking
      habits, physical exercise, occupational exposure to chemical products, use of
      personal safety equipment, and medical history of hepatitis, jaundice, and
      obesity. RESULTS: The prevalence of liver changes among refinery workers was
      15.3% (95% CI: 12.5 to 18.1), vs. 3.8% (95% CI: 1,8 to 5,8) in the reference
      population. According to multiple logistic regression analysis, the prevalence of
      liver changes among refinery workers was 3.56 times greater (95% CI: 1,99 to
      6,38) than in the reference population, regardless of the presence of other
      relevant co-variables, such as obesity, exercise, smoking, and alcohol
      consumption. CONCLUSIONS: These results suggest that occupational exposure may
      play a major role in the development of liver changes among workers at the oil
      refinery where the study was carried out.

PMID- 15720881
TI  - The epidemiologic transition in Peru.

PMID- 15720882
TI  - [The SAPUVET and SPVet networks: an integration model in veterinary public health
      between Europe and Latin America].

PMID- 15720883
TI  - A multidisciplinary approach to scaling up HIV/AIDS treatment and care: the
      experience of the Bahamas.

PMID- 15720884
TI  - Hypernatraemia in the breastfed infant.

PMID- 15720885
TI  - Recent advances in pneumococcal vaccination of children.
AB  - Pneumococcal disease is a major cause of childhood morbidity and mortality
      worldwide. However, there is a lack of epidemiological data to describe the
      vaccine-preventable burden of disease. New pneumococcal conjugate vaccines offer
      hope of preventing infant pneumococcal disease. The efficacy of the 7- and 9
      valent pneumococcal conjugate vaccine (PCV) against invasive vaccine-type
      pneumococcal disease in young children is between 77 and 97%. The PCV vaccine
      efficacy against radiological pneumonia in HIV-negative infants for the 7- or 9
      valent PCV is 23-30%. The vaccine efficacy in HIV-positive infants is lower--65%
      against invasive vaccine-type pneumococcal disease and no significant efficacy
      against radiological pneumonia. The 7-valent PCV showed modest efficacy against
      acute otitis media (7%) but seems to be more effective in preventing recurrent or
      severe disease. The high cost of these new vaccines is a barrier to their
      widespread introduction. The development of other pneumococcal vaccine candidates
      with wider serotype coverage should be encouraged. These vaccines should be
      affordable for all countries, particularly those with the highest burden of
      disease. In addition, other vaccination strategies such as maternal and neonatal
      immunisation and combinations of fewer doses of the PCV combined with an early
      dose of the cheaper pneumococcal polysaccharide vaccine need to be assessed
      further.

PMID- 15720886
TI  - Hypernatraemic dehydration in Jamaican breastfed neonates: a 12-year review in a
      baby-friendly hospital.
AB  - A 12-year retrospective review of neonates admitted with hypernatraemic
      dehydration to the neonatal unit of the University Hospital of the West Indies
      was conducted between 1 January 1990 and 31 December 2001. Twenty-four infants
      fulfilled the criteria for hypernatraemic dehydration. Nineteen (79%) women were
      either nulliparous or primiparous with a mean (SD) age of 26.9 (4.4) yrs. Modal
      length of hospital stay for mothers was 24 hrs. Twenty (83.3%) infants were
      exclusively breastfed. Mean (SD) age at presentation was 7.4 (3.8) days. Mean
      (SD) percentage weight loss between birth and presentation was 18.9% (6.3). Mean
      (SD) serum sodium at presentation was 164.8 (13.9) mmol/L. Babies visited at home
      by nurses had a lower mean serum sodium, were less dehydrated and were
      significantly less acidiotic. Their mean (SD) length of hospital stay was also
      significantly less [4.2 (1.4) days] than those who were not visited [7.9 (3.8)
      days] (p < 0.05). Complications occurred in 19 (79%) of infants and included
      renal failure (19, 79%), seizures (3, 13%) and intraventricular haemorrhage (1,
      4%), and one died (4%). Hypernatraemic dehydration is an uncommon complication of
      failure to establish breastfeeding but is associated with severe morbidity and
      mortality. Education programmes are needed to increase awareness amongst health
      care workers and mothers in order to prevent the problem.

PMID- 15720887
TI  - Haematological changes in African children who received short-term prophylaxis
      with nevirapine and zidovudine at birth.
AB  - We assessed the safety of short-term antiretroviral prophylaxis to prevent mother
      to-child transmission (MTCT) of HIV by monitoring haematological changes in
      children up to the age of 18 months. Babies of HIV-infected women were randomised
      at birth to receive a single dose of nevirapine (NVP) alone or with zidovudine
      (ZDV) twice daily for a week. Based on the time of presentation to the labour
      ward, mothers of these babies might or might not have received intrapartum NVP.
      Complete blood counts were performed at birth and at 1.5, 3, 6, 9, 12, 15 and 18
      months. Babies' HIV status was determined by HIV-1 RNA testing. A total of 1755
      babies were included in the study. Age-specific mean haemoglobin levels and
      prevalence of anaemia (haemoglobin < 10 g/dL) were not significantly different in
      cases where only the babies received a single dose of NVP and cases where NVP was
      given to mother/infant pairs or additional ZDV to the baby. Among HIV-infected
      children compared with uninfected children, the age-specific frequency of anaemia
      was significantly greater, anaemia started earlier and recovery to normal levels
      was slower and prolonged. A reversible granulocytopenia was observed in all
      children between 1.5 and 3 months of age. HIV infection significantly increased
      the children's risk of death. Antiretroviral prophylaxis appeared to protect
      against anaemia and child death. Short regimens of antiretrovirals to prevent
      MTCT of HIV are not associated with long-term adverse haematological changes.

PMID- 15720888
TI  - Risk factors for fetal anaemia in a malarious area of Malawi.
AB  - The prevalence of infants born with low cord haemoglobin (fetal anaemia) is high
      in areas where malaria and iron deficiency anaemia in pregnancy are common. The
      objective of the present study was to determine risk factors for fetal anaemia in
      an area of high malaria transmission in southern Malawi. A case control study was
      undertaken with fetal anaemia defined as cord haemoglobin (Hb) < 12.5 g/dl.
      Between March 1993 and July 1994, pregnant women attending the study hospitals
      for the first time in that pregnancy were enrolled. Data on socio-economic
      status, anthropometry, previous obstetric history and current pregnancy were
      collected. Malaria parasitaemia, Hb levels and iron status were measured in
      maternal blood at recruitment and delivery and in umbilical venous blood. Fetal
      anaemia occurred in 23.4% of babies. Mean (SD) cord Hb was 13.6 g/dl (1.83).
      Factors associated with fetal anaemia were: birth in the rainy season [adjusted
      odds ratio (AOR) 2.33, 95% CI 1.73-3.14], pre-term delivery (AOR 1.60, 1.03
      2.49), infant Hb < 14 g/dl at 24 hours (AOR 2.35, 1.20-4.59), maternal Hb at
      delivery < 8 g/dl (AOR 1.61, 1.10-2.42) or <11 g/dl (AOR 1.60, 1.10-2.31). A
      higher prevalence of fetal anaemia occurred with increasing peripheral Plasmodium
      falciparum parasite density (p=0.03) and geometric mean placental parasite
      densities were higher in babies with fetal anaemia than in those without (3331 vs
      2152 parasites/microl, p=0.07). Interventions should aim to reduce fetal anaemia
      by improving malaria and anaemia control in pregnancy and by addressing the
      determinants of pre-term delivery.

PMID- 15720889
TI  - Acute haemolytic crisis in a Thai patient with homozygous haemoglobin Constant
      Spring (Hb CS/CS): a case report.
AB  - Acute haemolysis associated with mild upper respiratory tract infection was
      observed in a Thai boy who presented with a rapid decline in haemoglobin (Hb)
      levels, haemoglobinuria and evidence of intravascular haemolysis. Several
      possible causes giving rise to such a condition were excluded including G6PD
      deficiency, which is extremely common in Thailand. Subsequent haematological and
      molecular analyses demonstrated that the patient was homozygous for Hb Constant
      Spring (Hb CS/CS), an a globin haemoglobinopathy. It has been shown previously
      that patients with homozygous Hb CS had mild haemolytic anaemia secondary to an
      accumulation of alpha(CS) chains, which are toxic to red blood cell membrane
      cytoskeletons. Increased body temperature might induce more precipitation of this
      a globin variant. This report highlights the importance of Hb CS/CS as a
      potential predisposing cause of acute haemolysis in children that might be
      aggravated by acute bacterial or viral infections. This is particularly relevant
      for patients of Southeast Asian descent where this abnormal haemoglobin is highly
      prevalent.

PMID- 15720890
TI  - Sonographic features of intestinal and biliary ascariasis in childhood: case
      report and review of the literature.
AB  - Despite the fact that Ascaris lumbricoides is one of the commonest intestinal
      infections in developing countries, there are very few reports in the literature
      about the sonographic findings of intestinal and biliary ascariasis in childhood.
      The clinical manifestations, diagnostic procedures and imaging appearance of
      intestinal and biliary ascariasis in two patients are discussed with a brief
      review of the literature.

PMID- 15720892
TI  - Four cases of neonatal non-ketotic hyperglycinaemia.
AB  - Non-ketotic hyperglycinaemia is an autosomal recessive disorder of glycine
      metabolism caused by a defect in the glycine cleavage system. Affected neonates
      present with lethargy, feeding difficulty, hypotonia, apnoea, poorly controlled
      convulsions and coma. Four cases are reported, three of whom died in the neonatal
      period. The fourth case was treated with dextromethorphan and sodium benzoate. He
      survived with neurodevelopmental delay but is now almost seizure-free.

PMID- 15720891
TI  - Serum cytokines in differentiating between viral and bacterial enterocolitis.
AB  - It is difficult to distinguish clinically between bacterial and viral causes of
      enterocolitis. The aim of the study was to investigate if serum cytokines can
      distinguish bacterial from viral enterocolitis. We prospectively enrolled 147
      paediatric in-patients with acute enterocolitis. Blood was taken for leucocyte
      count, CRP, ESR, IL-6, IL-8, IFN-alpha and TNF-alpha on the day of admission. A
      pathogen was identified in 115 of the 147 children, 72 of whom had a bacterial
      pathogen (bacterial group) and 43 rotavirus (viral group). Mean values of the
      serum markers IL-6, IL-8 and CRP were significantly higher in the bacterial
      group. Receiver-operating characteristic curves demonstrated that a cut-off of 15
      pg/ml for IL-6 had a sensitivity of 0.75 and a specificity of 0.91 for bacterial
      diarrhoea. Comparable values for CRP at a cut-off of 13 mg/L demonstrated a
      sensitivity of 0.54 and a specificity of 0.72. Values for IL-8 at a cut-off of 80
      pg/ml had a sensitivity of 0.46 and a specificity of 0.71. Despite the small
      sample size, our data suggest that serum IL-6, IL-8 and CRP are significantly
      elevated in children with bacterial enterocolitis. IL-6 has a higher sensitivity,
      specificity and positive predictive value than IL-8 and CRP. Determination of
      serum cytokines might be a useful way of differentiating viral from bacterial
      gastro-enteritis.

PMID- 15720893
TI  - Hypersensitivity pneumonitis in children: pigeon breeder's disease.
AB  - Hypersensitivity pneumonitis (HP), an extrinsic allergic alveolitis, is a group
      of immunologically mediated, diffuse inflammatory lung parenchymal diseases.
      Pigeon breeder's disease (PBD) is one of the most common clinical forms of HP. It
      is caused by inhalation of various pigeon-derived materials and can present in
      different clinical forms. The diagnosis is difficult and the best diagnostic tool
      is correlation of onset of symptoms with time of exposure. Precipitating
      antibodies against the avian proteins form the characteristic precipitin
      reactions. The most effective treatment is avoidance of the antigens. Steroids,
      either systemic or topical (inhalational), can be used to treat HP. We report
      five children with different clinical forms of PBD in whom the diagnosis was
      confirmed by positive serum precipitating antibodies to avian proteins. Although
      the disease is rarely seen in children, it should be considered in any child with
      recurrent or unexplained respiratory symptoms. Nebulising steroids might be a
      useful alternative treatment for allergic alveolitis.

PMID- 15720894
TI  - Thiamine deficiency: a cause of childhood ataxia not to be ignored.
AB  - We report four cases of childhood ataxia with and without encephalopathies which
      were successfully managed with thiamine supplementation and diagnosed in
      retrospect as being caused by thiamine deficiency. The clinical presentations
      were similar to those previously reported amongst adolescents and adults who
      ingested the larvae of Anaphe venata, a local delicacy among the Ijeshas of south
      western Nigeria, during the rainy season. This has been called seasonal ataxia
      syndrome. The cases were of interest because the disorder was not described in
      children in the previous report, which might indicate a worsening nutritional
      status in these communities. This report is to alert child health physicians in
      the developing world to the possibility of a pre-existing thiamine deficiency
      progressing into ataxic disorders when certain foods are ingested.

PMID- 15720895
TI  - Severe anaemia owing to hookworm in a 12-day-old Nepalese infant.

PMID- 15720897
TI  - Fresh plasma transfusion in the management of neonatal tetanus.

PMID- 15720896
TI  - Invasive group A streptococcal infections in children: an emerging infectious
      disease in Turkey.

PMID- 15720898
TI  - Is hypertriglyceridaemia a new concept for visceral leishmaniasis?

PMID- 15720899
TI  - Can performance as an undergraduate assist entry selection into surgical training
      programmes?

PMID- 15720900
TI  - How to approach major surgery where patients refuse blood transfusion (including
      Jehovah's Witnesses).
AB  - Jehovah's Witnesses do not permit the use of allogeneic blood products. An
      increasing number of patients are refusing blood transfusion for non-religious
      reasons. In addition, blood stores are decreasing, and costs are increasing.
      Transfusion avoidance strategies are, therefore, desirable. Bloodless surgery
      refers to the co-ordinated peri-operative care of patients aiming to avoid blood
      transfusion, and improve patient outcomes. These principles are likely to gain
      popularity, and become standard practice for all patients. This review offers a
      practical approach to the surgical management of Jehovah's Witnesses, and an
      introduction to the principles of bloodless surgery that can be applied to the
      management of all patients.

PMID- 15720901
TI  - Epigenetics, mismatch repair genes and colorectal cancer.
AB  - The recent discovery of hypermethylation of the promoter of genes is a powerful
      epigenetic mechanism for the inactivation of tumour suppressor genes in
      colorectal and other cancers. Approximately 95% of hereditary non-polyposis
      colorectal cancers (HNPCCs) and 15% of sporadic colorectal cancers (CRCs) are
      replication error positive (RER(+)). Although DNA mutations are found in mismatch
      repair genes in the majority of HNPCC CRC, mutations are rare in sporadic RER(+)
      CRCs. We have shown that the principal cause of an RER(+) phenotype is
      hypermethylation of the promoter of hMLH1, resulting in the absence of hMLH1
      protein. In contrast to sporadic RER(+) CRCs, we found that hypermethylation of
      hMLH1 does not occur in HNPCC CRC, suggesting the possibility of further
      differences between the two types of RER(+) tumours in the adenoma to carcinoma
      pathway. Other known tumour suppressor genes with few or no mutations may be
      candidates for epigenetic changes. One such gene is E-cadherin, and we described
      the first mutations of this gene in CRCs. Half of all CRCs were found to be
      hypermethylated in the Ecadherin promoter and this correlated with reduced E
      cadherin expression. Epigenetic changes occur in CRCs and arise in different
      frequencies in separate genes. Hypermethylation of the promoter may be reversed
      and gene function restored to a cell, thus partially undoing the cancer
      phenotype.

PMID- 15720902
TI  - The role of percutaneous nephrostomy in malignant ureteric obstruction.
AB  - OBJECTIVES: Uraemia as a result of malignant ureteric obstruction is a recognised
      event in those with advanced malignancy, usually of pelvic origin, which, if left
      untreated, is quickly a terminal event. Palliative decompression of the
      obstructed urinary system, either by percutaneous nephrostomy (PCN), ureteric
      stent or a combination of both is a recognised method of improving renal
      function, with presumed low morbidity. The aims of the study were to assess
      whether PCN placement in malignant ureteric obstruction provided any additional
      survival benefit or patient morbidity. PATIENTS AND METHODS: The case notes of 32
      patients with a mean age of 68.1 years (16 male, 16 female) who underwent PCN
      drainage for malignant ureteric obstruction were retrospectively analysed. Data
      on the site of primary malignancy, mode of presentation, improvement in renal
      function, median survival, conversion to internal ureteric stents and
      intervention-related complications were collected for analysis. RESULTS: The
      median survival following PCN insertion was 87 days and was unrelated to the
      patient's age and renal function. Those patients with primary underlying
      gynaecological malignancies appeared to survive almost 4 times as long as those
      with underlying primary bladder cancer. Renal function took a mean of 16.8 days
      to reach a nadir. Almost 79% of patients were able to be discharged from hospital
      -each patient, however, being re-admitted back to hospital on average 1.6 times
      prior to their death through PCN or internal ureteric stent related events.
      Retrospective "useful quality of life" was seen in less than half of the patient
      cohort. CONCLUSIONS: In the presence of malignant ureteric obstruction,
      palliative percutaneous urinary diversion may be performed and is effective in
      improving renal function. However, long-term survival is limited and should,
      therefore, be performed only when the views and wishes of the patient and carers
      are taken into account and if there is a definitive treatment plan available for
      the patient as quality of life can be suboptimal.

PMID- 15720903
TI  - Ultrasound-guided insertion of subclavian venous access ports.
AB  - INTRODUCTION: Central venous cannulation is an integral part of venous access
      port (portacath) placement for intravenous chemotherapy. NICE guidelines have
      suggested that CVC should be performed under ultrasound guidance. The technique
      of ultrasound-guided subclavian cannulation is reviewed and our experience
      presented. PATIENTS AND METHODS: Retrospective analysis of data on patients
      undergoing ultrasound-guided portacath placement for the failure rate and the
      incidence of complications. RESULTS: We were successful in cannulating the
      subclavian vein in 44 of 55 patients. There was one arterial puncture and no
      haemothorax or pneumothorax with the technique (complication rate 1.8%).
      CONCLUSION: An ultrasound-guided approach should be the standard technique for
      central venous cannulation in portacath placement.

PMID- 15720904
TI  - Are we overusing blood transfusing after elective joint replacement?--a simple
      method to reduce the use of a scarce resource.
AB  - OBJECTIVES: To determine the proportion of patients who received a blood
      transfusion after joint replacement, and to devise a simple method to ensure
      patients were transfused based on strict clinical and haematological need.
      DESIGN: Prospective audit over 2 years. PATIENTS AND METHODS: The study group was
      151 patients who underwent total hip and knee arthroplasty in a typical district
      general hospital (Kettering) over a 2-year period. They were divided into three
      consecutive groups. Current practice was audited (producing the first group of 62
      patients) and transfusion rates were compared to regional figures. Local
      guidelines were drawn up. A form was introduced on which the indications for any
      transfusion had to be documented prior to transfusion of the blood. This was
      designed to encourage transfusion only on strong clinical grounds or an
      haemoglobin (Hb) level < 8 g/dl. Transfusion practice was then re-audited
      (producing the second group of 44 patients) to assess whether practice had
      improved. A year later, all relevant staff were reminded by letter of the
      guidelines. The process was then re-audited (producing the third group of 45
      patients) again to determine whether practice remained improved or not. RESULTS:
      In the first audit (current practice) of 62 patients, the overall transfusion
      rate was 71%, with a higher rate in the hip replacement group (84%) ordered
      mainly by anaesthetic staff. Ward staff were reluctant not to transfuse patients
      whose Hb level fell below 10 g/dl. In the second audit, the transfusion rate fell
      by nearly 50% to 37%, with almost identical figures for knee and hip replacement.
      In the third audit of 45 patients, a year later, the transfusion rate was 40%
      overall. CONCLUSIONS: Patients were being transfused routinely, generally without
      good clinical evidence of benefit to the patient. The audit process was
      successful in instituting change for the better in blood transfusion practice for
      elective joint replacement. The improved practice can be largely maintained
      provided staff are regularly reminded of appropriate guidelines and encouraged to
      transfuse for clinical need only. For absolute adherence to guidelines, we would
      recommend a compulsory form system be introduced for transfusion in the per
      operative period, to ensure blood transfusion is only given when absolutely
      necessary.

PMID- 15720905
TI  - Early failure of total hip replacements implanted at distant hospitals to reduce
      waiting lists.
AB  - AIM: In the years 1990-1993, in an effort to reduce waiting-list time, a small
      number of patients were sent from Exeter to hospitals in London to undergo
      elective total hip replacement. No medium- or long-term follow-up was arranged.
      Our aim was to audit the outcome of these hip replacements. PATIENTS AND METHODS:
      Review of the records of the referring medical practices, Regional Health
      Authority, local orthopaedic hospital and the distant centres at which the
      surgery was performed identified 31 cases. A total of 27 hip replacements in 24
      patients were available for clinical and radiological review. RESULTS: 12 (44%)
      hips have so far required revision surgery, at a mean of 6.5 years. Of these,
      three (11%) have been for deep infection. A further three hips (11%) are
      radiologically loose and are being closely monitored. Two patients (7%) suffered
      permanent sciatic nerve palsy. CONCLUSIONS: Patients whose surgery was performed
      locally over a similar time period have a published failure rate of only 4.9%.
      This difference is highly statistically significant (P < 0.001). The causes for
      such a difference in outcome were analysed and include surgical technique,
      implant selection and absence of follow-up. In the light of this evidence, we
      would like to urge the government to address waiting list problems by investing
      in the local infrastructure. Expanding those facilities where properly audited
      and fully accountable surgeons operate must be the way forward.

PMID- 15720906
TI  - Carpal tunnel syndrome, the search for a cost-effective surgical intervention: a
      randomised controlled trial.
AB  - OBJECTIVE: There is insufficient evidence regarding the clinical and cost
      effectiveness of surgical interventions for carpal tunnel syndrome. This study
      evaluates the cost, effectiveness and cost-effectiveness of minimally invasive
      surgery compared with conventional open surgery. PATIENTS AND METHODS: 194
      sufferers (208 hands) of carpal tunnel syndrome were randomly assigned to each
      treatment option. A self-administered questionnaire assessed the severity of
      patients' symptoms and functional status pre- and postoperatively. Treatment
      costs were estimated from resource use and hospital financial data. RESULTS:
      Minimally invasive carpal tunnel decompression is marginally more effective than
      open surgery in terms of functional status, but not significantly so. Little
      improvement in symptom severity was recorded for either intervention. Minimally
      invasive surgery was found to be significantly more costly than open surgery. The
      incremental cost effectiveness ratio for functional status was estimated to be
      197 UK pounds, such that a one percentage point improvement in functioning costs
      197 UK pounds when using the minimally invasive technique. CONCLUSIONS: Minimally
      invasive carpal tunnel decompression appears to be more effective but more
      costly. Initial analysis suggests that the additional expense for such a small
      improvement in function and no improvement in symptoms would not be regarded as
      value-for-money, such that minimally invasive carpal tunnel release is unlikely
      to be considered a cost-effective alternative to the traditional open surgery
      procedure.

PMID- 15720907
TI  - Orthopaedic surgeons in Yorkshire--are we ATLS positive?
AB  - INTRODUCTION: In 1993, the Major Trauma Working Group of Yorkshire proposed that
      hospitals should be accredited as Trauma Reception Hospitals with a policy for
      the response to the arrival of a trauma patient. These requirements include
      specific criteria for orthopaedics. METHODS: To evaluate if these criteria are
      being fulfilled, we carried out an audit comparing the response in the hospitals
      within the Yorkshire deanery to the arrival of major trauma. All consultant and
      middle-grade orthopaedic surgeons on call for trauma were contacted and
      questioned as to their ATLS provider status and involvement in the "trauma call".
      RESULTS: 16 hospitals were included of which 13 have a "trauma team". 191
      surgeons (96% response) were included. 175 have completed an ATLS course. Of
      these, 72 (41%) had out-of-date qualifications. Only 9 (13%) were waiting to
      revalidate. Variation was seen in the frequency of accident and emergency
      department attendance by different grades of surgeon for major trauma.
      DISCUSSION: All hospitals have a response for major trauma although variations
      occur. The vast majority of orthopaedic surgeons in Yorkshire have been
      adequately trained in ATLS management (more so than any study has previously
      shown), particularly the middle grades, who are usually first to attend. The
      level of revalidation is low and reasons for this are discussed with
      recommendations for revalidation in the future.

PMID- 15720908
TI  - Reconstruction of through-and-through osteocutaneous defects of the mouth and
      face with subscapular system flaps.
AB  - BACKGROUND: Major ablative surgery in the head and neck region may create
      composite defects involving the oral mucosa, bone and the overlying facial skin.
      The large surface area and the three-dimensional nature of these defects pose a
      difficult reconstructive challenge requiring adequate bone and large,
      positionally versatile skin flaps. PATIENTS AND METHODS: From September 1993 to
      May 2000, 19 patients with through-and-through osteocutaneous defects of the
      mouth and face were reconstructed with composite subscapular artery system flaps.
      The evaluated parameters included: (i) site and dimensions of the tissue defect;
      (ii) specific flap properties; and (iii) review of the recipient and donor site
      morbidity. RESULTS: 10 variants of scapular osteocutaneous flaps, eight
      latissimus dorsi with serratus anterior and rib osteo-myocutaneous flaps, and one
      combination of an osteocutaneous scapular and myocutaneous latissimus dorsi flap
      were used to reconstruct composite facial defects with mean dimensions of: skin
      54.4 cm(2), mucosa 56.2 cm(2) and bone of 8.2 cm. Ischaemic complications
      occurred in three patients including one total flap failure and one failure of
      the bony component in previously irradiated patients. The third flap was
      successfully salvaged. No significant long-term donor site morbidity was noted.
      CONCLUSION: Composite flaps based on the subscapular artery system are a
      versatile reconstructive modality for large through-and-through defects of the
      mouth and face.

PMID- 15720909
TI  - Effect of introduction of digital radiographic techniques on pre-operative
      templating in orthopaedic practice.
AB  - AIM: To assess whether the introduction of digital radiographic acquisition has
      altered the magnification of pelvic radiographs compared to standard acquisition
      techniques, and whether this influences preoperative implant templating for total
      hip arthroplasty. SETTING: District general hospital orthopaedic out-patient
      department. PATIENTS AND METHODS: 51 sets of patient radiographs were studied,
      where digital and standard radiographic techniques had been used for each
      patient. Key bony landmarks were measured, the scaled ruler analysed and the
      femur templated to gauge the most appropriate implant size of implant. RESULTS:
      Introduction of digital techniques has resulted in a mean magnification of 97%,
      whereas most manufacturers' templates assume a magnification of 115-120%. For the
      Exeter femoral component, the templated size showed only moderate correlation
      with that templated from a standard radiograph (kappa index 0.46), although the
      offset templated showed good correlation (kappa index 0.89). CONCLUSIONS:
      Surgeons should be aware that introduction of digital techniques of radiograph
      acquisition may reduce the magnification of the film and, therefore, reduce the
      accuracy of pre-operative templates supplied by the manufacturers of implants,
      resulting in incorrect selection of implants.

PMID- 15720910
TI  - NICE news in the Annals.

PMID- 15720911
TI  - Inguinal hernia--laparoscopic or open repair? The case for laparoscopic repair.

PMID- 15720913
TI  - Training in the Calman era: what consultants say.

PMID- 15720914
TI  - Abdominal complications from crack cocaine.

PMID- 15720915
TI  - Mobile messaging: emergency image transfer.

PMID- 15720916
TI  - Rectal infiltration by prostatic adenocarcinoma: a report on six patients and
      review of the literature.

PMID- 15720917
TI  - Hip osteoarthritis: where is the pain?--Letter 2.

PMID- 15720918
TI  - Hip osteoarthritis: where is the pain?--Letter 1.

PMID- 15720919
TI  - Atypical giant cell arteritis resulting in arm amputation.

PMID- 15720920
TI  - Displaced paediatric supracondylar fractures of the humerus--response to a sticky
      solution.

PMID- 15720922
TI  - Preparing digital images for publication.

PMID- 15720923
TI  - Emergency treatment of ankle fracture dislocations--a reliable technique for
      early reduction.

PMID- 15720925
TI  - After Shipman: reforming the GMC--again.

PMID- 15720926
TI  - Human metapneumovirus.

PMID- 15720927
TI  - The National Programme for Information Technology: the GP as gatekeeper--a
      bastion worth fighting for?

PMID- 15720928
TI  - A qualitative study of migraine involving patient researchers.
AB  - BACKGROUND: Migraine is poorly managed in primary care despite a high level of
      morbidity. The majority of sufferers use non-prescription medications and are
      reluctant to seek help but the reasons for this are not understood. AIM: The aim
      of this study was to develop a research partnership between migraine sufferers
      and healthcare professionals to synthesise tacit and explicit knowledge in the
      area. Building upon this partnership, a further aim was to explore what it is to
      suffer with migraine from patients' perspectives in order to inform health
      service delivery. DESIGN: Qualitative interview study involving healthcare
      professionals and patient researchers. SETTING: A purposeful sample of eight
      migraine sufferers who had attended a local intermediate care headache clinic.
      METHOD: A consensual qualitative approach. RESULTS: Migraine had a high and
      unrecognised impact on quality of life. 'Handling the beast' was a central
      metaphor that resonated with the experience of all sufferers who sought to
      control their problem in different ways. Three major themes were identified:
      making sense of their problem; actively doing something about it either through
      self-help or professional advice; being resigned to it. CONCLUSION: Despite a
      significant impact on the quality of life of migraine sufferers and their
      families, their needs remain largely unmet. Useful insights can be obtained when
      patients and professionals work together in true partnership but the time and
      effort involved should not be underestimated. Further research is needed to
      identify why there are major deficiencies in delivering care in this common
      problem.

PMID- 15720929
TI  - Improving management of hypertension in general practice: a randomised controlled
      trial of feedback derived from electronic patient data.
AB  - BACKGROUND: Although absolute risk of death associated with raised blood pressure
      increases with age, the benefits of treatment are greater in older patients.
      However, fewer patients in this group are identified, treated, and controlled.
      AIM: To evaluate the impact of the provision of different levels of feedback on
      identification, treatment, and control of older patients with hypertension.
      DESIGN OF STUDY: Randomised controlled trial. SETTING: Fifty-two Scottish general
      practices. METHOD: Practices were randomly allocated to either control (n = 19),
      audit only feedback (n = 16), or audit plus risk feedback, prioritising patients
      by absolute risk (n = 17). Electronic data were extracted from practice computer
      systems annually from 1999 to 2001 and used to develop feedback. Data were
      collected for 30 345 patients aged 65-79 years. RESULTS: The majority of known
      patients with hypertension in each group had an initial blood pressure recorded
      (control = 89.6%; audit = 80.4%; risk = 96.1%) and this increased over the study
      period (control = 92.3%; audit = 86.0%; risk = 96.6%). Initially, more than 80%
      of patients in each group were treated but many were uncontrolled (blood pressure
      >/=160/ >/=90 mmHg) (control = 41.5%; audit = 41.3%; risk = 36.1%). The numbers
      of untreated and uncontrolled patients in each group reduced (control = 32.3%;
      audit = 38.3%; risk = 32.6%). There was some evidence of a significant difference
      in mean systolic pressure between the audit plus risk and audit only groups:
      (149.6 versus 152.7 mmHg; P = 0.019) and of significantly greater control in the
      audit plus risk group compared with the other groups 49.4% (versus audit only =
      35.4%; versus control = 46.5%; odds ratio = 1.72 [95% confidence interval = 1.09
      to 2.70]; P = 0.019). CONCLUSIONS: Levels of identification, treatment, and
      control improved in each group. Although there were still significant numbers of
      patients with uncontrolled hypertension, there is some evidence to suggest that
      providing patient-specific feedback may have a positive impact on identification
      and management of hypertension in older people and produce an increase in
      control.

PMID- 15720930
TI  - Is herpes zoster a marker for occult or subsequent malignancy?
AB  - BACKGROUND: It has been suggested that herpes zoster may be a marker for occult
      malignancy. AIM: To examine the emergence of a subsequent cancer diagnosis in
      patients with and without herpes zoster. DESIGN OF STUDY: Retrospective cohort
      study. SETTING: Results were based on the database of Intego, an ongoing Belgian
      general practice-based morbidity registry, covering 37 general practitioners and
      including about 311 000 patient years between the years 1994 and 2000. METHOD:
      Survival analysis comparing the emergence of malignancy in patients with and
      without herpes zoster. RESULTS: The number of patients below the age of 65 years
      with herpes zoster, cancer or both was too low to draw any sensible conclusions.
      Above the age of 65 years we identified a significant increase of cancer
      emergence in the whole group and in females (hazard ratio = 2.65, 95% confidence
      interval = 1.43 to 4.90), but not in males. No difference could be identified in
      the first year after the herpes zoster infection. CONCLUSION: Our results do not
      justify extensive testing for cancer in herpes zoster patients. The association
      we identified, however, leaves open a number of questions with respect to the
      physiopathology behind it.

PMID- 15720931
TI  - Primary care consultation predictors in men and women: a cohort study.
AB  - BACKGROUND: Women visit their doctors more than men, but comparatively few
      studies have explored gender differences in consultation in detail. AIMS: To
      identify the factors that predicted the number of primary care consultations in
      men and women over a 5-year period. DESIGN OF STUDY: Prospective cohort study
      with three waves of data collection by postal questionnaire. SETTING: A single
      suburban general practice in Greater Manchester, UK. METHOD: Consultation data
      were sought from primary care records on a random sample of 800 adults. The main
      outcome measure was the number of consultations over the 5 years of the study.
      Questionnaire measures included the 12-item version of the General Health
      Questionnaire, the Illness Attitude Scales, a somatic symptom scale, a fatigue
      scale, and a functional assessment of disability. RESULTS: Consultation data were
      obtained on 738 patients (445 women, 293 men, 92% of selected subjects).
      Longitudinal models of consultation over 5 years showed that changes in
      psychological distress were more strongly associated with consultation in women
      than in men, whereas cognitive factors (negative illness attitudes) were more
      strongly associated with the consultation rate in men than women. CONCLUSION: The
      predictors of consultation in primary care may be different for men and women. A
      fuller understanding of the reasons for consultation may enable primary care
      doctors to better help individual patients, as well as perhaps contributing more
      generally to the development of gender specific interventions for those who
      consult unusually frequently.

PMID- 15720932
TI  - Prescribing antibiotics for respiratory tract infections by GPs: management and
      prescriber characteristics.
AB  - BACKGROUND: Due to clinical and non-clinical factors, considerable variation
      exists in the prescribing of antibiotics for respiratory tract infections (RTIs)
      by GPs based in the Netherlands. AIM: To assess, in patients with RTIs in Dutch
      general practice: the prescribing rates of antibiotics; the relationship between
      GP characteristics and antibiotic prescribing; and the type of antibiotics
      prescribed. DESIGN OF STUDY: Descriptive and prognostic. SETTING: Eighty-four GPs
      in the middle region of the Netherlands. METHOD: All patient consultations for
      RTIs were registered by 84 GPs during 3 weeks in autumn and winter 2001 and 2002.
      In addition, all GPs completed a questionnaire related to individual and practice
      characteristics. RESULTS: The mean proportion of consultations in which GPs
      prescribed antibiotics was 33% (95% CI = 29 to 35%) of all RTIs. This proportion
      varied from 21% for patients with upper RTIs or an exacerbation of asthma/COPD,
      to about 70% when patients had sinusitis-like complaints or pneumonia.
      Amoxycillin and doxycycline were the most frequently prescribed antibiotics,
      while 17% of the antibiotics prescribed were macrolides. Multiple linear
      regression analysis showed that the longer GPs had practised, the more frequently
      they prescribed antibiotics, especially in combination with relatively little
      knowledge about RTIs or the less time GPs felt they had available per patient.
      The final model, with seven factors, explained 29% of the variance of antibiotic
      prescribing. CONCLUSION: The prescribing behaviour of Dutch GPs might be improved
      with regard to choice of type and indication of antibiotics.

PMID- 15720933
TI  - Cost-effectiveness of telephone or surgery asthma reviews: economic analysis of a
      randomised controlled trial.
AB  - BACKGROUND: Only about a third of people with asthma attend an annual review.
      Clinicians need to identify cost-effective ways to improve access and ensure
      regular review. AIM: To compare the cost-effectiveness of nurse-led telephone
      with face-to-face asthma reviews. DESIGN OF STUDY: Cost-effectiveness analysis
      based on a 3-month randomised controlled trial. SETTING: Four general practices
      in England. METHOD: Adults due an asthma review were randomised to telephone or
      face-to-face consultations. Trial nurses recorded proportion reviewed, duration
      of consultation, and abortive calls/missed appointments. Data on use of
      healthcare resources were extracted from GP records. Cost-effectiveness was
      assessed from the health service perspective; sensitivity analyses were based on
      proportion reviewed and duration of consultation. RESULTS: A total of 278 people
      with asthma were randomised to surgery (n = 141) or telephone (n = 137) review.
      Onehundred-and-one (74%) of those with asthma in the telephone group were
      reviewed versus 68 (48%) in the surgery group (P <0.001). Telephone consultations
      were significantly shorter (mean duration telephone = 11.19 minutes [standard
      deviation {SD} = 4.79] versus surgery = 21.87 minutes [SD = 6.85], P <0.001).
      Total respiratory healthcare costs per patient over 3 months were similar
      (telephone = pounds sterling 64.49 [SD = 73.33] versus surgery = pounds sterling
      59.48 [SD = 66.02], P = 0.55). Total costs of providing 101 telephone versus 68
      face-to-face asthma reviews were also similar (telephone = pounds sterling 725.84
      versus surgery = pounds sterling 755.70), but mean cost per consultation achieved
      was lower in the telephone arm (telephone = pounds sterling 7.19 [SD = 2.49]
      versus surgery = pounds sterling 11.11 [SD = 3.50]; mean difference = - pounds
      sterling 3.92 [95% confidence interval = - pounds sterling 4.84 to pounds
      sterling 3.01], P <0.001). CONCLUSIONS: Telephone consultations enable a greater
      proportion of asthma patients to be reviewed at no additional cost to the health
      service. This mode of delivering care improves access and reduces cost per
      consultation achieved.

PMID- 15720934
TI  - Accuracy of specific IgE in the prediction of asthma: development of a scoring
      formula for general practice.
AB  - BACKGROUND: For the diagnosis of asthma in young children, GPs have to rely on
      history taking and physical examination, as spirometry is not possible. The
      additional diagnostic value of specific immunoglobulin E (IgE) to inhalent
      allergens remains unclear. AIM: To assess the predictive accuracy of specific IgE
      to cat, dog, and/or house dust mites in young children for the subsequent
      development of asthma at the age of 6 years. DESIGN OF STUDY: Prospective follow
      up study. SETTING: Seventy-two general practices. METHOD: A total of 654
      children, aged 1-4 years, visiting their GPs for persistent coughing (>/= 5
      days), were tested for IgE antibodies by radio allergosorbent testing (RAST).
      Parents completed a questionnaire on potential risk indicators. Those children
      who showed an IgE-positive status (12.7%) and a random sample of those with an
      IgE-negative status (<0.5 U/ml) were followed up to the age of 6 years when the
      asthma status was established. The main outcome measure was asthma at the age of
      6 years (combination of both symptoms and/or use of asthma medication, and
      impaired lung function). RESULTS: Addition of RAST results to a prediction model
      based on age, wheeze, and family history of pollen allergy increased the area
      under the receiver operating characteristic (ROC) curve from 0.76 to 0.87.
      Furthermore, RAST improved patient differentiation as indicated by a change in
      the range of asthma probabilities from 6-75% before the IgE test, to 1-95% after
      the IgE-test. CONCLUSION: Sensitisation to inhalant allergens in 1-4-year-olds,
      as shown by RAST, is a useful diagnostic indicator for the presence of asthma at
      the age of 6 years, even after a clinical history has been obtained. This model
      should preferably be validated in a new population before it can be applied in
      practice.

PMID- 15720935
TI  - The diagnostic dilemma of Parkinson's disease as a cause of calf 'claudication'.

PMID- 15720936
TI  - Isotretinoin, depression and suicide: a review of the evidence.
AB  - There is currently considerable controversy regarding a proposed causal
      relationship between the use of isotretinoin and depression and suicide. A search
      was made of the MEDLINE, EMBASE and PsychINFO databases using the search terms
      'isotretinoin', 'depression' and 'suicide'. Despite numerous case reports linking
      isotretinoin to depression, suicidal ideation and suicide, there is, as yet, no
      clear proof of an association. While isotretinoin, used to treat acne vulgaris,
      has not been demonstrated to be associated with depression or suicide, the
      possibility of a relatively rare idiosyncratic adverse effect remains. GPs have a
      role in the clinical application of these findings.

PMID- 15720938
TI  - The act of communicating.

PMID- 15720937
TI  - The effectiveness of community maintenance with methadone or buprenorphine for
      treating opiate dependence.
AB  - BACKGROUND: Opiate dependence is a major health and social issue in many
      countries. A mainstay of therapy has been methadone maintenance treatment, but
      other treatments, particularly buprenorphine, are increasingly being considered.
      AIM: To conduct a systematic review to synthesise and critically appraise the
      evidence on the effectiveness of community maintenance programmes with methadone
      or buprenorphine in treating opiate dependence. METHOD: A systematic review of
      databases, journals and the grey literature was carried out from 1990-2002.
      Inclusion criteria were: community-based, randomised controlled trials of
      methadone and/or buprenorphine for opiate dependence involving subjects who were
      aged 18 years old or over. RESULTS: Trials were set in a range of countries,
      employed a variety of comparators, and suffered from a number of biases. The
      evidence indicated that higher doses of methadone and buprenorphine are
      associated with better treatment outcomes. Low-dose methadone (20 mg per day) is
      less effective than buprenorphine (2-8 mg per day). Higher doses of methadone
      (>50-65 mg per day) are slightly more effective than buprenorphine (2-8 mg per
      day). There was some evidence that primary care could be an effective setting to
      provide this treatment, but such evidence was sparse. CONCLUSION: The literature
      supports the effectiveness of substitute prescribing with methadone or
      buprenorphine in treating opiate dependence. Evidence is also emerging that the
      provision of methadone or buprenorphine by primary care physicians is feasible
      and may be effective.

PMID- 15720939
TI  - Dirty magazines.

PMID- 15720940
TI  - GPs on the move.

PMID- 15720941
TI  - Backing Bush.

PMID- 15720942
TI  - The duty to die cheaply.

PMID- 15720943
TI  - Reflections on the GP Registrar Year.

PMID- 15720944
TI  - Heroes and villains.

PMID- 15720945
TI  - A doctor-ridden Godforsaken race.

PMID- 15720948
TI  - Conversations imagined and remembered.

PMID- 15720949
TI  - Towards a definition of holism.

PMID- 15720952
TI  - Another one bites the dust.

PMID- 15720951
TI  - A Sage move--at last.

PMID- 15720954
TI  - PGEA is dead, long live PGE!

PMID- 15720956
TI  - The incidence and characteristics of recombinant erythropoietin-associated pure
      red-cell aplasia.

PMID- 15720955
TI  - Platelet bleeding disorders and approach to their management.

PMID- 15720957
TI  - Anemia in HIV-infected adults: epidemiology, pathogenesis, and clinical
      management.
AB  - Anemia is the most common cytopenia seen in people with HIV. Independent of CD4
      count and HIV-viral load, anemia has been shown to correlate with increased
      mortality. Furthermore, successful treatment of anemia has been shown to reduce
      this risk of death in a comparison with patients with similar immunologic and
      virologic parameters who are not treated. Women, blacks, injection drug users,
      and people with advanced disease suffer disproportionally from anemia and should
      be screened. The pathogenesis of anemia in HIV is complex and may result from
      opportunistic infections, nutritional deficiencies, AIDS-associated malignancies,
      medications, or alteration in hematopoeisis induced by HIV itself. A careful
      review of the patient's past medical history, medications, symptoms, and basic
      laboratory studies often leads to a treatable cause(s). For patients without
      secondary causes of anemia, a combination of highly active antiretroviral therapy
      (HAART) and supplemental erythropoietin leads to improved outcomes. Given the
      importance of completing therapy on adequate doses of both interferon and
      ribavirin, effective management of anemia in HIV/Hepatitis C (HCV)-coinfected
      patients is particularly important.

PMID- 15720958
TI  - Paroxysmal nocturnal hemoglobinuria: current issues in pathophysiology and
      treatment.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the
      bone marrow that produces intravascular hemolysis, proclivity to venous
      thrombosis, and hematopoietic failure. Mutation in the PIG-A gene in a stem cell
      aborts synthesis of glycosyl-phosphoinositol (GPI) anchors and therefore
      expression of all GPI-anchored proteins on the surface of progeny erythrocytes,
      leukocytes, and platelets. The hemolytic anemia of PNH is well understood, and
      erythrocyte susceptibility to complement may be treated with anti-C5a monoclonal
      antibody. The pathophysiology of PNH cell clonal expansion and its association
      with immune-mediated marrow failure are not understood, but PNH/aplasia responds
      to immunosuppressive regimens such as antithymocyte globulin and cyclosporine.
      The mechanism of thrombosis in PNH is also obscure, but frequently fatal clotting
      episodes may be prevented by Coumadin (Bristol-Myers Squibb Pharma Co.,
      Wilmington, DE) prophylaxis.

PMID- 15720959
TI  - Iron chelation therapy.
AB  - Although iron chelation therapy with deferoxamine (DFO) has changed life
      expectancy in thalassemic patients, compliance with the rigorous requirements of
      long-term subcutaneous DFO infusions is unsatisfactory. This problem underlines
      the current efforts for developing alternative, orally effective chelators to
      improve compliance and treatment results. For the patient with transfusional iron
      overload in whom results of DFO treatment are unsatisfactory, several orally
      effective agents are now available. The most important of the new generation of
      oral chelators are deferiprone and ICL670. Total iron excretion with deferiprone
      is less than with DFO, but deferiprone has a better ability to penetrate cell
      membranes and may have a better cardioprotective effect than DFO. Current studies
      of the clinical efficacy and tolerability of ICL670 indicate that at a single
      oral dose of 20 mg/kg daily, it may be as effective as parenteral DFO used at the
      standard dose of 40 mg/kg daily. Combined chelation treatment, employing a weak
      chelator that penetrates cells better, and a stronger chelator with efficient
      urinary excretion, may result in improved therapeutic effect through iron
      shuttling between the two compounds. The efficacy of combined chelation treatment
      is additive and offers an increased likelihood of success in patients previously
      failing DFO or deferiprone monotherapy.

PMID- 15720960
TI  - Hemolytic anemia-associated pulmonary hypertension in sickle cell disease.
AB  - Pulmonary hypertension is one of the leading causes of death in adult sickle cell
      patients, with a prevalence of 20% to 40%. Although these patients have lower
      pulmonary pressures than patients with primary pulmonary hypertension, both
      groups suffer high 2-year mortality rates. Pulmonary hypertension may go
      undetected until the disease is advanced. Therefore, all adult patients with
      sickle cell disease should be screened with transthoracic Doppler echocardiogram
      and the tricuspid regurgitant jet (TRJ) velocity measured to estimate pulmonary
      artery pressures. A regurgitant jet (RJ) velocity of 2.5 m/s or higher
      establishes diagnosis and suggests a high risk of death (rate ratio of 10.1; CI=
      2.2-47). Basic and epidemiologic studies suggest that pulmonary hypertension in
      sickle cell disease is mechanistically linked to chronic hemolytic anemia.
      Hemolysis results in the release of hemoglobin and arginase from the erythrocyte,
      increasing the consumption and decreasing the production of nitric oxide (NO),
      respectively. NO is a critical regulator of vasodilation and vascular homeostasis
      whose inactivation produces vasoconstriction and proliferative vasculopathy.
      Finally, we review suggested therapies including the established treatments and
      new pulmonary vasodilator and remodeling agents in the management of pulmonary
      hypertension in hemolytic anemias.

PMID- 15720961
TI  - Stem cell transplantation and gene therapy for hemoglobinopathies.
AB  - The b-thalassemias and sickle cell disorders are the most common genetic diseases
      worldwide. Although improvements in conservative treatment have considerably
      improved the prognosis of hemoglobinopathies, stem cell transplantation remains
      the only cure for thalassemia and sickle cell disease. Results of transplants in
      these diseases have steadily improved over the last two decades due to
      improvements in preventive strategies, effective control of transplant-related
      complications and development of new preparative regimens. High-resolution human
      leukocyte antigen (HLA) typing has enabled physicians to perform transplant from
      unrelated volunteer donors for thalassemia with results comparable with those
      obtained employing an HLA-identical sibling. Current understandings of stable
      mixed chimerism (MC) in patients with hemoglobinopathies provide a rationale for
      the use of less intensive conditioning regimens and future gene therapy. Despite
      recent advances in animal models, the clinical application of gene therapy for
      hemoglobinopathies is unlikely to be a reality for at least near future. With the
      advances in transplantation for thalassemia, all sickle cell disease patients
      should be offered stem cell transplantation with an human leukocyte antigen (HLA)
      identical donor. This review focuses on the current status of stem cell
      transplantation for hemoglobinopathies.

PMID- 15720962
TI  - Platelet transfusions for bleeding during coronary artery bypass graft surgery.

PMID- 15720963
TI  - Thrombopoietic growth factors and cytokines.
AB  - Chemotherapy-induced thrombocytopenia is largely managed with platelet
      transfusions and reductions of chemotherapy doses. In the last decade, several
      thrombopoietic cytokines have been investigated without much success.
      Thrombopoietin (TPO), a key physiologic regulator of platelet production, is
      found to be the most potent thrombopoietic cytokine studied so far.
      Unfortunately, the clinical development of recombinant human thrombopietin has
      met challenges related to the biology of TPO with a delayed peak platelet
      response and the findings of neutralizing antibodies to the pegylated molecule.
      Recent clinical studies showed the importance of TPO schedule in relation to
      chemotherapy. Also, recombinant TPO facilitated collection of platelets in normal
      donors and patients for transfusions. The initial trials in leukemia or
      transplant settings did not impact the need for platelet transfusions. Future
      developments of TPO and mimetics will require carefully designed clinical trials
      with the consideration of unique biology of TPO and the time lag for a peak
      platelet response.

PMID- 15720964
TI  - Thrombocytopenia in dengue fever.
AB  - Dengue is probably the most important arthropod-borne viral disease in terms of
      human morbidity and mortality. We review the pathophysiology of thrombocytopenia
      and clinical bleeding in dengue across the spectrum of disease. The mechanisms of
      thrombocytopenia and coagulopathy are complex, involving platelet activation,
      procoagulant and anticoagulant arms of the coagulation system, complement,
      cytokines, and endothelial cells. Platelet counts do not correlate well with
      clinical bleeding. Although serious bleeding is rare, patients should be
      monitored closely for hemorrhagic manifestations and thrombocytopenia.
      Symptomatic thrombocytopenia may require platelet transfusion.

PMID- 15720965
TI  - HIV Infection and thrombocytopenia.
AB  - Thrombocytopenia is a common complication of HIV infection. The low platelet
      count can be caused by multiple mechanisms including immune-mediated destruction,
      decreased platelet production, effects of drugs on progenitors, or by the
      development of a form of thrombotic thrombocytopenic purpura (TTP). Bleeding
      problems associated with the thrombocytopenia can be accentuated by the presence
      of platelet dysfunction produced by drugs used to treat HIV/AIDs or its
      complications. Therapy should be directed at reducing the load of the HIV virus
      of the patient supplemented by other therapies chosen depending on the specific
      underlying cause.

PMID- 15720966
TI  - Post-transfusion purpura.
AB  - Post-transfusion purpura (PTP) is a rare bleeding disorder caused by
      alloantibodies specific to platelet antigens. The antibody against the human
      platelet alloantigen (HPA)-1a is responsible for most of the cases. The majority
      of affected patients are multiparous women who presumably have been previously
      sensitized during pregnancy. Blood transfusions rarely have been implicated as
      the primary cause for alloimmunization in PTP. Thrombocytopenia is usually severe
      and resolves spontaneously within several weeks. However, patients may develop
      severe if not fatal bleeding during the course of this disease. The diagnosis is
      confirmed by demonstrating that the patient's serum contains antibodies to
      platelet-specific antigens. Treatments for PTP include intravenous
      immunoglobulin, corticosteroids, and plasmapheresis.

PMID- 15720967
TI  - The role of antiplatelet autoantibody assays in the diagnosis of immune
      thrombocytopenic purpura.
AB  - Immune thrombocytopenic purpura (ITP) is a disorder almost always manifested by
      antibody-induced thrombocytopenia. In 1987, two clinically useful antigen
      specific assays were reported, the immunobead assay and the monoclonal antibody
      specific immobilization of platelet antigens (MAIPA) assay. These two assays and
      their variations give similar results and can measure both platelet-associated
      and plasma antibodies. Three prospective studies have reported assay results with
      sensitivities ranging from 49% to 66% and specificities ranging from 78% to 93%.
      Most antibodies react with either platelet glycoprotein (GP) IIb/IIIa or GPIb/IX.
      Recent evidence suggests that antiplatelet antibody assays may also be useful in
      predicting disease prognosis. Rare ITP patients have bleeding with normal or near
      normal platelet counts, a prolonged bleeding time, and aggregation abnormalities
      due to autoantibodies that affect platelet function. Incubation of patient
      plasma, IgG or eluate with normal platelet-rich plasma reproduces the patient's
      aggregation abnormalities.

PMID- 15720968
TI  - How Mannheimia haemolytica defeats host defence through a kiss of death
      mechanism.
AB  - Mannheimia haemolytica induced pneumonias are only observed in goats, sheep and
      cattle. The bacterium produces several virulence factors,whose principal ones are
      lipopolysaccharide and leukotoxin. The latter is cytotoxic only for ruminant
      leukocytes, a phenomenon that is correlated with its ability to bind and interact
      with the ruminant beta2-integrin Lymphocyte Function-associated Antigen 1. This
      paper globally reviews all the information available on host-pathogen
      interactions underlying respiratory mannheimiosis (formerly pasteurellosis), from
      the stable and the Petri dish to the biochemical cascade of events triggered by
      the leukotoxin inside ruminant leukocytes. One conclusion can be made: the most
      widespread cattle respiratory disease with the most important impact on beef
      production worldwide, is probably due to a tiny ruminant-specific focal variation
      in the CD18- and/or CD11a-expressing genes.

PMID- 15720969
TI  - Administration of Duddingtonia flagrans chlamydospores to goats to control gastro
      intestinal nematodes: dose trials.
AB  - The ability of the nematophagous fungus Duddingtonia flagrans to reduce the
      number of infective nematode larvae in coproculture was investigated in goats
      using different doses of chlamydospores (0, 1.25 x 10(5), 2.5 x 10(5), 5 x 10(5)
      chlamydospores/kg BW/day) given by oral administration or by voluntary
      consumption in feed during natural or experimental infections with nematodes. The
      kinetics of excretion of D. flagrans chlamydospores in the faeces was also
      determined using a dose of 5 x 10(5) chlamydospores/kg BW/day for five days. For
      all the trials, the faecal nematode egg outputs were determined by a modified
      McMaster method and standard coprocultures were set up (14 days, 25 degrees C) to
      determine the number of larvae emerging from culture in fungus treated and
      control faeces. When chlamydospores were orally administered, the number of
      larvae were reduced by 50 to 97% when compared to control cultures. No difference
      in the level of larval emergence from the culture was seen for experimental or
      natural infections at the different chlamydospore dose rates. In contrast, when
      chlamydospores were distributed in the feed, a dose-dependent relationship was
      observed 10 days after the start of administration, the larval development being
      2.0%, 14.0% and 86.9% for 5 x 10(5), 2.5 x 10(5) and 0 spores/kg BW/day,
      respectively. In addition, the kinetic study showed that the larval emergence
      from coproculture in the fungus group was statistically lower than in the control
      group from the second day of administration of the chlamydospores and remained
      lower until the second day after the last administration (p < 0.05). The results
      indicate that, for goats in farm conditions, a minimum daily dose of 5 x 10(5)
      chlamydospores/kg BW must be used to ensure a high treatment efficacy and that
      daily administration is preferable for maintenance of efficacy over time.

PMID- 15720970
TI  - Dose dependency and individual variability in selected clinical, haematological
      and blood biochemical responses after systemic lipopolysaccharide challenge in
      cattle.
AB  - Previous studies have noted that susceptibility to systemic lipopolysaccharide
      (LPS) exposure seems to differ between individual cows. However, to date inter
      individual variation in the response to intravenous injection of LPS has been
      reported only as an empirical finding, and its existence or extent has never been
      backed up by statistical analyses. The aim of the present study was therefore to
      investigate the dose-dependency of clinical, haematological and blood biochemical
      responses to intravenous LPS injection in dairy cattle and to determine the
      extent to which these responses differed between individual cows. Eight dairy
      cows each received three intravenous injections of Escherichia coli LPS (10, 100,
      and 1000 ng/kg, consecutively) at three-week intervals. All three LPS doses
      induced clinical, haematological, and blood biochemical responses lasting up to
      several days. The strength of all of the responses increased significantly with
      an increasing LPS dose. A statistically significant inter-individual variation
      was demonstrated for all clinical, haematological, and blood biochemical
      responses except for serum calcium concentrations. More than half of the
      statistical variation in white blood cell and thrombocyte counts could be
      attributed to the individual. The results of this study show that despite the
      existence of a dose-response relationship between LPS and ensuing clinical,
      haematological, and blood biochemical responses, the majority of responses to LPS
      differ significantly in strength and duration from cow to cow.

PMID- 15720971
TI  - Effect of breed and gender on bovine liver cytochrome P450 3A (CYP3A) expression
      and inter-species comparison with other domestic ruminants.
AB  - The cytochrome P450 (P450) superfamily represents a group of relevant enzymes in
      the field of drug metabolism and several exogenous or constitutional factors
      contribute to regulate its expression. Cattle represent an important source of
      animal-derived food-products and studies concerning the P450 expression are
      needed for the extrapolation of pharmacotoxicological data from one species to
      another and for the evaluation of the consumer's risk associated with the
      consumption of harmful residues found in foodstuffs. In the present study,
      possible breed-, gender- and species-differences in P4503A (the P450 subfamily
      more expressed in the human liver) expression were studied in vitro in
      Piedmontese (PDM) and Limousin (LIM) meat cattle breeds of both sexes and in
      domestic Ruminants (cattle, sheep and goats). Cytochrome P450 and P4503A contents
      as well as CYP3A-dependent drug metabolising enzymes (DME) were measured in liver
      microsomes. Significant lower levels of P450 (P < 0.001) and P4503A (P < 0.05)
      contents were observed in PDM vs. LIM of both sexes; the P4503A-dependent DME
      activities were significantly (P values ranging from 0.05 up to 0.001) higher in
      PDM cattle, particularly in males. A gender-effect in DME activities was noticed
      (P < 0.05) only in PDM male cattle. With regards to the species, the expression
      of both P4503A apoprotein and some of the related DME activities were more
      pronounced in sheep (P < 0.01 vs. cattle) and in goats (P < 0.05 vs. sheep; P <
      0.01 vs. cattle) than in cattle. The significant differences in P4503A expression
      observed in LIM and PDM cattle are consistent with previously published data on
      strain- and breed-differences pointed out in rats and men. As far as a possible
      sex-effect is concerned, no clear-cut evidence is likely to be drawn. Finally,
      P4503A expression was more relevant in small ruminants.

PMID- 15720972
TI  - Haptoglobin and serum amyloid A in milk from dairy cows with chronic sub-clinical
      mastitis.
AB  - New tools are needed to detect chronic sub-clinical mastitis, especially in
      automatic milking systems. Haptoglobin and serum amyloid A (SAA) are the two most
      sensitive bovine acute phase proteins, and their concentrations increase in milk
      from cows with clinical mastitis and in milk from cows with experimentally
      induced chronic sub-clinical Staphylococcus aureus mastitis. The aim of this
      study was to further evaluate the potential for haptoglobin and SAA in milk as
      indicators of chronic sub-clinical mastitis. Quarter milk samples were collected
      from 41 cows with a mean composite milk somatic cell count (CSCC) above 300,000
      cells/mL during at least two months prior to sampling. Quarter milk samples were
      also taken from eleven cows with a mean CSCC below 80,000 cells/mL during at
      least two previous months. These samples were analysed for haptoglobin, SAA,
      adenosine triphosphate (ATP) activity and bacterial growth. The samples were
      grouped according to their ATP, haptoglobin and SAA status. ATP+ samples had ATP
      > 2 x 10(-10) mol/mL, Hp+ and SAA+ samples had detectable levels of haptoglobin
      (> or = 0.3 mg/L) and SAA (> or = 0.9 mg/L), respectively. In udder quarter
      samples from healthy cows, 42 out of 44 samples belonged to the ATP-Hp-SAA-
      group. Among cows with chronic sub-clinical mastitis, the ATP+Hp+SAA+ group
      contained 66 out of 164 samples while 44 samples belonged to the ATP+Hp-SAA-
      group. Detectable levels of haptoglobin and SAA were found in 92 and 80 samples,
      respectively. Growth of udder pathogens was detected in 28 samples and
      Staphylococcus aureus was the most common bacteria. In conclusion, haptoglobin
      and SAA concentrations below the detection limit were considered as good
      indicators of healthy udder quarters. A substantial variation in haptoglobin and
      SAA concentrations in milk was observed in udder quarters with chronic sub
      clinical mastitis.

PMID- 15720973
TI  - A pharmaco-epidemiological analysis of factors associated with antimicrobial
      consumption level in turkey broiler flocks.
AB  - An on-farm pharmaco-epidemiological survey of 246 turkey broiler flocks from 131
      farms was carried out to assess the homogeneity of antimicrobial use between
      flocks on the same farm and to explore the possible relationships between farm
      and farmer characteristics and the level of antimicrobial use. The antimicrobial
      use in each flock was quantified by an invoice study, expressed as the number of
      national animal daily doses (ADD)/turkey broiler and characterised as "high",
      "medium" or "low" according to the tertiles of the resulting distribution.
      Antimicrobial use was then correlated with variables collected from the farmer by
      means of an alternating logistic regression method which calculates the pairwise
      odds ratio (PWOR) for within-farm clustering. Two independent models were fitted:
      (1) "low" versus "medium" + "high" antimicrobial consumption and (2) "high"
      versus "medium" + "low" antimicrobial consumption. PWOR from the null models were
      significant (P < 0.005), but only remained significant in the first final model
      (P = 0.002). Four explanatory variables were retained for both models.
      Prophylactic antimicrobial administration and veterinarian antimicrobial
      prescription attaining the farm technical staff's expectation were associated
      with a higher antimicrobial consumption level. Administration of competitive
      exclusion flora and compliance with biosecurity rules of changing clothes and
      shoes before entering the facilities, were associated with a lower antimicrobial
      consumption level. In the first model, the number of full-time jobs devoted to
      the turkey production unit (1 versus more than 1) was also found to be associated
      with the antimicrobial consumption level. The study tends to confirm the
      feasibility of the adopted approach to quantify antimicrobial use and to
      determine the factors likely to influence antimicrobial consumption.

PMID- 15720974
TI  - The bovine viral diarrhea virus (BVDV) NS3 protein, when expressed alone in
      mammalian cells, induces apoptosis which correlates with caspase-8 and caspase-9
      activation.
AB  - The bovine viral diarrhea virus (BVDV) strains exist as two biotypes, cytopathic
      (cp) and noncytopathic (ncp), according to their effects on tissue culture cells.
      It has been previously reported that cell death associated to cp BVDV in vitro is
      mediated by apoptosis. Here, experiments were conducted to determine the
      involvement of the NS3 protein in the induction of apoptosis. The NS3- and
      NS3Delta50 (deleted from the NH2-terminal 50 amino acids)-cDNA encoding sequences
      of BVDV NADL cp reference strain were cloned into adenoviral vectors (AdV) from
      which the BVDV gene of interest could be expressed from a tetracycline-responsive
      promoter. A549tTA cells infected in vitro with NS3 or NS3Delta50-expressing AdV
      showed cytopathic changes characterized by cell rounding and detachment, and
      nucleus chromatin condensation. DNA fragmentation assays, cytochrome c release,
      and activation of cellular caspases performed on these infected cells clearly
      correlated with the observed cytopathic changes with apoptosis. The BVDV
      NS3Delta50-induced apoptotic process was inhibited by caspase-8- and -9-specific
      peptide inhibitors (Z-IETD-FMK and Z-LEHD-FMK). Furthermore, apoptosis was
      inhibited in cells expressing the R1 subunit of herpes simplex virus type 2
      ribonucleotide reductase (HSV2-R1) or hsp70, two proteins which are known to
      inhibit apoptosis associated with caspase-8 activation and cytochrome c release
      dependent caspase-9 activation, respectively. Given that HSV2-R1, a specific
      inhibitor of the caspase-8 activation pathway, efficiently suppressed apoptosis
      and also prevented caspase-9 activation, the overall results indicate that the
      BVDV NS3/NS3Delta50 induces apoptosis initiated by caspase-8 activation and
      subsequent cytochrome c release-dependent caspase-9 activation.

PMID- 15720976
TI  - Characterizing the APEC pathotype.
AB  - The purpose of this study was to compare avian pathogenic Escherichia coli (APEC)
      isolates to fecal isolates of apparently healthy poultry (avian fecal E. coli or
      AFEC) by their possession of various traits in order to ascertain whether APEC
      and AFEC are distinct and if the APEC strains constitute a distinct pathotype.
      Four hundred and fifty-one APEC and one hundred and four AFEC isolates were
      examined for possession of traits associated with the virulence of human
      extraintestinal pathogenic E. coli (ExPEC) as well as APEC. Several of the genes
      occurred in the majority of APEC and only infrequently in AFEC, including cvaC,
      iroN, iss, iutA, sitA, tsh, fyuA, irp2, and ompT. Of these genes, several have
      been found on large plasmids in APEC. Other genes occurred in significantly more
      APEC than AFEC but did not occur in the majority of APEC. Isolates were also
      evaluated by serogroup, lactose utilization, and hemolytic reaction. Twenty-nine
      and a half percent of the APEC and forty-two and three tenths percent of the AFEC
      were not serogrouped because they were not typeable with standard antisera, typed
      to multiple serogroups, were rough, autoagglutinated, or were not done. Around
      65% of the typeable APEC (205 isolates) and AFEC (41 isolates) were classified
      into shared serogroups, and about a third of both fell into APEC- (113 isolates)
      or AFEC- (19 isolates) unique serogroups. Most were able to use lactose. No
      isolate was hemolytic. Overall, the majority of the APEC isolates surveyed shared
      a common set of putative virulence genes, many of which have been localized to an
      APEC plasmid known as pTJ100. This common set of genes may prove useful in
      defining an APEC pathotype.

PMID- 15720975
TI  - NF-kappaB inhibition accelerates apoptosis of bovine neutrophils.
AB  - Apoptosis is one of the major events that contribute to the regulation of the
      immune system. For human neutrophils, evidence has been produced that the
      transcription factor NF-kappaB is critical in influencing the ultimate outcome of
      a cell's fate. However, such research has not yet been performed on bovine
      neutrophils. This urged us to examine the possible involvement of NF-kappaB in
      apoptosis of these cells. At first, we investigated whether p65 and p50, the most
      important members of the NF-kappaB family, are expressed in isolated blood
      neutrophils. The presence of both members was demonstrated on the RNA and protein
      level. Then the effect on bovine neutrophil apoptosis of gliotoxin, a potent and
      specific inhibitor of NF-kappaB, was examined. The rate of constitutive apoptosis
      was found to be greatly accelerated by inhibition of NF-kappaB. Furthermore,
      gliotoxin dramatically augmented the limited pro-apoptotic effect of TNF-alpha,
      an important inflammatory mediator. The results were obtained in six cows by
      annexin-V-FITC staining of externalized phosphatidylserine and subsequent flow
      cytometric analysis. Additional measurement of caspase-3/7 activity and
      evaluation of morphological criteria confirmed the outcome of this experiment.
      Finally, NF-kappaB activity was assessed under these conditions. The activity of
      p50 was found to be minimally affected by gliotoxin, while significantly lower
      active p65 values were observed. Still, the highest percentage of apoptosis,
      which was caused by incubation with both gliotoxin and TNF-alpha, did not
      correspond to the lowest activity of p65. We conclude that NF-kappaB p65 promotes
      the survival of bovine neutrophils by delaying the initiation of apoptosis.

PMID- 15720977
TI  - Ketamine inhibits LPS-induced tumour necrosis factor-alpha and interleukin-6 in
      an equine macrophage cell line.
AB  - Ketamine is widely used in equine anaesthesia. Beside its anaesthetic and
      analgesic properties, ketamine possesses a cytokine-modulating activity. However,
      to date, no data are available regarding the inhibitory effect of ketamine on the
      cytokine response in horses. In horses, cytokines such as tumour necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) play a pivotal role in the
      pathogenesis of equine endotoxaemia following gastrointestinal disorders. Hence,
      the objective of this study was to assess the influence of ketamine on LPS
      induced TNF-alpha and IL-6 formation in an equine macrophage cell line (eCAS
      cells). The results demonstrate a cytokine-modulating activity of ketamine in an
      equine cell line, suggesting a beneficial role for ketamine in the treatment of
      equine endotoxaemia.

PMID- 15720978
TI  - Has implementation of the 80-hour work week made a career in surgery more
      appealing to medical students?
AB  - BACKGROUND: This study was conducted to determine if a surgical career became
      more appealing to medical students with the resident work week limited to 80
      hours. METHODS: At the start and conclusion of each surgery clerkship rotation,
      students completed a survey addressing perception of surgeons, and surgery as a
      career. They were divided into the control groups (rotations before July 2003; n
      = 109) and the experimental group (rotations after July 2003; n = 108). RESULTS:
      Students in the experimental group had a significantly more favorable impression
      of a surgeon's lifestyle and work hours than those in the control group. This was
      especially true of female students post-rotation, who responded more positively
      to the statement that a surgical career would allow for a good balance between
      professional and personal life (1.87 vs 2.45, P <.01). CONCLUSION: The new
      Accreditation Council for Graduate Medical Education (ACGME) regulation has had a
      positive impact on students' perceptions of the surgeon's lifestyle, but does not
      necessarily increase their interest in a surgical career.

PMID- 15720979
TI  - How do residents manage personal finances?
AB  - BACKGROUND: We examined three research questions: How do residents' debts and
      savings compare to the general public? How do surgical residents' financial
      choices compare to other residents? How may institutions help residents' personal
      financial decisions? METHODS: The Survey of Consumer Finances was modified and
      piloted tested to elicit financial information. The instrument was completed by
      612 residents at 8 programs. RESULTS: Only 60% of residents budgeted expenses,
      and 25% and 10% maintained cash balances <611 dollars and unpaid credit card
      balances >10,000 dollars, respectively. Compared with controls, residents held
      greater median ratios of debt to household income (2.46 vs. 1.06, P <0.0001),
      fewer assets to income (0.64 vs. 2.28, P <0.0001), less net wealth to income 
      1.43 vs. 0.90, P <0.0001), and lower retirement savings balance to household
      income (0.01 vs. 0.12, P <0.0001). Surgery residents were the least financially
      conservative group. Mean annual resident contributions to retirement accounts
      were $1532 higher at institutions with versus without retirement plans (P <0.01).
      CONCLUSIONS: Resident debts are higher and savings lower than the general public.
      This behavior is most common among surgery residents. Residents save more for
      retirement when they are eligible for tax-deferred retirement plans. Graduate
      medical programs should instruct residents on financial management.

PMID- 15720980
TI  - Endovascular treatment of abdominal aortic aneurysms.
AB  - BACKGROUND: Endovascular treatment of abdominal aortic aneurysms is a rapidly
      evolving technique that has gained broad acceptance in the treatment of patients
      with abdominal aortic aneurysms. METHODS: A review of the English literature was
      done to determine the short- and long-term outcomes of endovascular repair of
      abdominal aortic aneurysms. Reports of complications such as endoleak, graft
      migration, graft limb occlusion, aneurysm rupture, and aneurysm enlargement were
      evaluated. RESULTS: Short-term results of endovascular repair of abdominal aortic
      aneurysms are excellent. The necessity for open conversions is less than 5%. The
      cumulative risk of aneurysm rupture is approximately 1% per year. The coverall
      incidence of graft limb occlusion was 2.8% in the follow-up period. The
      cumulative risk for a secondary procedure was 12% at 1 year, 24% at 2 years, and
      35% at 3 years. Moderate and severe neck angulation was associated with an
      increased incidence of adverse events in the follow-up period. Endografts have
      the potential to become infected and develop aortoduodenal fistula. The treatment
      of ruptured aneurysms with endovascular grafts has been successful and a
      technique that is increasingly used. CONCLUSION: Endovascular treatment of
      abdominal aortic aneurysm is an effective technique with excellent short-term
      results. The long-term results remain to be determined. Ongoing surveillance is
      necessary to avoid late complications of aneurysm rupture.

PMID- 15720981
TI  - Surgical treatment of infected aneurysms and pseudoaneurysms of the thoracic and
      abdominal aorta.
AB  - BACKGROUND: To review the outcome of infected aneurysms and pseudoaneurysms of
      the thoracic and abdominal aorta treated in a major teaching hospital. METHODS:
      Between December 1994 and January 2003, 13 infected aortic aneurysms and
      pseudoaneurysms (5 thoracic, 4 paravisceral, 4 infrarenal) in 10 consecutive
      patients were treated surgically. Aortic debridement with in situ reconstruction
      is our standard practice. Endovascular repair was offered to suitable patients
      with thoracic aortic involvement. RESULTS: There were six men and four women with
      a mean age of 63 years. The commonest pathogen was Salmonella species, accounting
      for 50% of the cases. Aortic debridement with in situ revascularization was
      performed for six patients with visceral reconstruction in four of them. One
      patient with aortic bifurcation involvement and gross purulent infection had
      ligation and debridement followed by right axillobifemoral bypass. Four infected
      thoracic aortic pseudoaneurysms in three other patients underwent endovascular
      repair. There was no hospital death, limb loss, renal failure, or intestinal
      ischemia. There were two late deaths from sepsis and pneumonia at 3 months and 77
      months after operation. Eight patients were alive after a mean follow-up of 36
      months and no late graft infection was evident. CONCLUSIONS: Surgical treatment
      for infected aortic aneurysms with in situ reconstruction is associated with
      favorable outcome and good long-term result. Endovascular repair has a potential
      role.

PMID- 15720982
TI  - An evaluation of low molecular weight heparin and hyperbaric oxygen treatment in
      the prevention of intra-abdominal adhesions and wound healing.
AB  - BACKGROUND: Abdominal surgery can lead to intra-abdominal adhesions with
      significant morbidity and mortality. To prevent adhesions, an experimental study
      was planned to designate the effects of low molecular weight (LMW) heparins and
      hyperbaric oxygen (HBO) therapy both on the formation of adhesions and wound
      healing. METHODS: Thirty-eight Wistar albino rats underwent laparotomy to cause
      intra-abdominal adhesions by mechanical abrasion of the cecum and ethanol
      application. The rats were divided into 4 groups. In the control group (group 1)
      no further management was undertaken. Group 2 was treated by Enoxaparine Na,
      group 3 received HBO therapy, and group 4 was given both enoxaparine Na and HBO
      treatment. RESULTS: There was a statistically significant difference between the
      control and enoxaparine Na groups regarding adhesions. Statistically significant
      differences were observed between groups 1 and 4 and between groups 1 and 3
      regarding the hydroxyproline content of the abdominal wounds. In the pathologic
      analysis of the abdominal wounds, there was no statistically significant
      difference between any of the groups, including the control group, regarding
      inflammation. Statistically significant differences were observed regarding
      angiogenesis between the control group and groups 3 and 4. There was also a
      statistically significant difference regarding fibrosis between groups 1 and 4.
      CONCLUSIONS: Enoxaparine Na decreased intra-abdominal adhesions, and HBO therapy
      had no beneficial effect on adhesions. Enoxaparine Na had no harmful effects on
      wound healing, and HBO therapy increased the process of wound healing.

PMID- 15720983
TI  - Antithrombin III attenuates pulmonary tissue injury caused by mesenteric ischemia
      reperfusion.
AB  - BACKGROUND: Mesenteric ischemia-reperfusion (I/R) is a well-known event causing
      both local and remote organ injuries, including the lungs. Recently, several
      studies indicated that activated leukocyte-endothelial cell interactions play an
      important role in the mechanisms of these injuries. As a natural inhibitor of
      serine proteases, antithrombin was shown previously to attenuate the tissue
      damage after local I/R in several organ systems. Here, we examined the effects of
      antithrombin on pulmonary injury after mesenteric I/R. METHODS: Wistar albino
      rats underwent median laparotomy and were randomized into 3 groups: (1) sham
      operated control (n = 12), (2) 60 minutes of mesenteric ischemia and 3 hours of
      reperfusion (n = 12), and (3) antithrombin-pretreated (250 U/kg) group before the
      I/R (n = 12). At the end of reperfusion, animals were killed and neutrophil
      sequestration, myeloperoxidase (MPO) activity, and Evans blue dye extravasation
      in the lung parenchyma were assessed and compared. RESULTS: There was a
      statistically significant increase in the quantity of Evans blue dye
      concentration, leukocyte sequestration, and MPO activity in the I/R group when
      compared with the control group. The pretreatment of animals with antithrombin
      significantly decreased the pulmonary injury characterized by increased Evans
      blue dye extravasation, leukocyte sequestration, and MPO activity. CONCLUSION:
      The data of the present study suggest that mesenteric ischemia and reperfusion
      induces pulmonary injury characterized by activated neutrophil sequestration and
      increased microvascular leakage in the lungs. A significant attenuation of
      intestinal I/R-related lung injury with the use of antithrombin concentrate
      warrants further studies to elucidate the potential role of this natural serine
      protease inhibitor in clinical settings.

PMID- 15720984
TI  - Indications of partial hepatectomy for transplantable hepatocellular carcinoma
      with compensated cirrhosis.
AB  - BACKGROUND: The appropriate treatment strategy for transplantable hepatocellular
      carcinoma (HCC) patients with compensated cirrhosis remains controversial.
      METHODS: Surgical outcomes were reviewed in 136 cirrhotic patients with
      transplantable HCC who had undergone partial hepatectomy. Transplantable HCC was
      defined as that corresponding to Milan's criteria. RESULTS: The adverse
      prognostic factors for both survival and disease-free survival were histologic
      surgical margin of 5 mm or less, Child-Pugh B, and the presence of hepatitis C
      virus infection. The overall 5-year survival and disease-free survival rates of
      patients with 1 or none of the adverse prognostic factors were 73% and 33%,
      respectively, whereas those of patients with 2 or 3 adverse prognostic factors
      were 36% and 17%, respectively. CONCLUSIONS: Transplantable HCC patients with 2
      or 3 adverse prognostic factors should be considered candidates for liver
      transplantation, whereas patients with only 1 or none of the adverse prognostic
      factors are good candidates for partial hepatectomy.

PMID- 15720985
TI  - Treatment and outcome of intrahepatic cholangiocellular carcinoma.
AB  - BACKGROUND: Treating intrahepatic cholangiocarcinoma (ihCCC) tumor resection
      leads to the best patient survival. The aim of this study was to investigate
      prognostic factors in resected patients. METHODS: This was a clinical
      observational series of 31 resected patients with ihCCC. Univariate analysis of
      clinical and pathologic factors in relation to patient survival and tumor
      recurrence were performed. Possible benefit of chemotherapy, although not given
      randomly, was investigated separately. RESULTS: The median follow-up time was
      37.3 months. Of 31 resected patients a tumor-free resection (R0) was achieved in
      26; 2 patients died postoperatively. Chemotherapy was administered to 19
      patients. Overall survival was significantly better in patients with R0
      resection, negative lymph nodes, a solitary tumor, and a width of resection
      margin greater than 3 mm. Recurrence-free survival was prolonged in patients with
      negative lymph nodes, early International Union Against Cancer (UICC) stages and
      solitary tumors. In UICC stages III and IV, patients receiving chemotherapy
      experienced a better overall survival. CONCLUSIONS: Impact of various parameters
      on recurrence-free and overall survival was identified; a possible beneficial
      effect of adjuvant chemotherapy in advanced tumor stages was observed. A
      prospective, randomized trial is necessary to fully evaluate the role of adjuvant
      therapy.

PMID- 15720986
TI  - A secure technique of intracorporeal Roux-Y reconstruction after laparoscopic
      distal gastrectomy.
AB  - BACKGROUND: Laparoscopic distal gastrectomy [LDG] is a minimally invasive surgery
      for gastric carcinoma. The Billroth I method has been commonly employed to
      reconstruct alimentary tract after LDG. Conversely, Roux-Y reconstruction is
      employed far less commonly despite its merits. Technical difficulties, including
      a risk of twisting the Roux loop under limited vision through a laparoscope, have
      hampered Roux-Y reconstruction after LDG. METHODS: We performed LDG and
      intracorporeal Roux-Y reconstruction in 5 patients with early gastric cancer. The
      procedure included a functional end-to-end anastmosis of the stomach and jejunum,
      consisting of side-to-side approximation of jejunal loop to greater curvature of
      the gastric remnant with a laparoscopic stapling device followed by closure of
      the open end and simultaneous division of the jejunum with another stapler.
      RESULTS: Roux-Y reconstruction was successfully accomplished without torsion of
      the loop in all patients. CONCLUSIONS: By using the present technique,
      intracorporeal Roux-Y reconstruction after LDG can be accomplished without a risk
      of twisting the jejunal loop.

PMID- 15720987
TI  - Is the learning curve for laparoscopic fundoplication determined by the teacher
      or the pupil?
AB  - BACKGROUND: For all surgical procedures, a surgeons' learning curve can be
      anticipated during which complication rates are increased. The aims of this study
      were to evaluate individual learning curves for a group of surgeons performing
      laparoscopic fundoplication and to evaluate if the Procedicus MIST-simulator
      (Mentice Inc., Goteborg, Sweden) accurately predicts surgical performance.
      METHODS: Twelve Nordic centers participated, each contributing with a "master"
      and a "pupil" surgeon. The pupils were tested in the simulator and thereafter
      performed their first 20 supervised operations. All procedures were videotaped
      and evaluated by 3 independent reviewers. RESULTS: A significant decrease in
      operative time (P <0.001) and a trend (P = 0.12) toward improved score were seen
      during the series. The master significantly affected the pupil's score (P
      =0.0137). The simulator-test showed no correlation with the operative score.
      CONCLUSIONS: Individual learning curves varied, and the teacher was shown to be
      the most important factor influencing the pupil's performance score. The
      correlation between assessed performance and patient outcome will be further
      investigated.

PMID- 15720988
TI  - Laparoscopic liver resection of hepatocellular carcinoma.
AB  - BACKGROUND: We have continued to develop laparoscopic hepatectomy as a means of
      surgical therapy for hepatocellular carcinoma (HCC). METHODS: We evaluated the
      degree of invasiveness and analyzed the outcomes of laparoscopic hepatectomy
      compared with open hepatectomy for HCC. RESULTS: There were notable differences
      with respect to blood loss and operating time compared with open hepatectomy
      cases. Patients started walking and eating significantly earlier in the
      laparoscopic hepatectomy group, and these more rapid recoveries allowed shorter
      hospitalizations. On the Estimation of Physiologic Ability and Surgical Stress (E
      PASS) scoring system, there was no difference in preoperative risk. However, a
      significant difference was seen in the surgical stress and comprehensive risk
      scores between the open hepatectomy and laparoscopic hepatectomy groups.
      Concerning the survival rate and disease-free survival rate, there were no
      significant differences between procedures. CONCLUSIONS: Laparoscopic hepatectomy
      avoids some of the disadvantages of open hepatectomy and is beneficial for
      patient quality of life (QOL) as a minimally invasive procedure if the operative
      indications are appropriately based on preoperative liver function and the
      location and size of HCC.

PMID- 15720989
TI  - Proposal for a reclassification of liver based anatomy on portal ramifications.
AB  - BACKGROUND: Portal branching patterns that differ from those previously described
      are occasionally encountered during liver surgery. METHODS: A total of 60
      patients with normal intrahepatic venous anatomy underwent helical computed
      tomography during arterial portography (CTAP). Next, 3 dimensional portograms
      were reconstructed to verify the locations of the portal veins. Portal branching
      patterns in the right hemiliver were assessed. RESULTS: In all 60 patients
      examined, the right anterior portal vein bifurcated into the ventral and dorsal
      branches. In 42 (70%) of 60 patients, some branches arose from the right
      posterior portal trunk. Between 1 and 3 branches (mean 2.3 branches per patient)
      coursed cranially, between 2 and 5 branches (mean 3.2 branches per patient)
      coursed caudally, and between 1 and 2 branches (mean 1.3 branches per patient)
      coursed laterally. CONCLUSIONS: We propose that the right liver should be divided
      into 3 segments, which are designated as the right anterior, middle, and
      posterior segments.

PMID- 15720990
TI  - A safe and reliable technique for visualization of the laryngeal recurrent nerves
      in the neck.
AB  - BACKGROUND: The risk of an injury of the laryngeal recurrent nerve is an
      important issue during any surgical procedure in the lower neck. METHODS: Based
      on our experience with the transcervical-subxiphoid bilateral videothoracoscopic
      maximal thymectomies, we developed an original technique of visualization for
      both of these nerves. The key point of the presented technique is the dissection
      in the lower part of the neck, beneath the level of the thyroid gland. The
      central step is the division of the deep cervical fascial layers covering and
      obscuring the recurrent nerves. Preservation of the deepest layer protects the
      nerves from an injury. RESULTS: We used this technique in 100 consecutive
      transcervical-subxiphoid bilateral videothoracoscopic maximal thymectomies
      without any case of permanent recurrent nerve palsy. CONCLUSION: The presented
      technique is safe, reliable, and relatively simple. It may be used during an
      extended thymectomy, as well as during a thyroid resection and other operations
      in the lower neck.

PMID- 15720991
TI  - Recurrent pleomorphic adenoma of the parotid gland.
AB  - BACKGROUND: Surgery of recurrent pleomorphic adenoma presents an increased risk
      of facial nerve injury and a considerable re-recurrence rate. METHODS: A series
      of 33 patients with first recurrence of pleomorphic adenoma of the parotid gland
      was analyzed. The data were derived from medical records as well as from
      interviews and clinical examinations of all living patients. Histologic material
      of the initial and recurrent tumor were reviewed. RESULTS: Multifocal recurrence
      and carcinoma in pleomorphic adenoma were observed in 73% and 9% of patients,
      respectively. The incidence of permanent partial facial nerve injury after
      surgery was 23% in patients with initial enucleation and 14% in those with
      initial superficial parotidectomy (including 1 patient with facial nerve
      resection and 1 patient with a partial facial paresis before recurrence surgery).
      A subsequent recurrence occurred in 6 patients, all with initial enucleation
      after a mean time interval of 9 years. CONCLUSIONS: The preservation of the
      facial nerve was possible in all but 1 patient treated for the first recurrence
      with a relatively low rate of permanent partial facial paresis because of the use
      of the operating microscope and facial nerve monitor. To evaluate the re
      recurrence rate, a follow-up of at least 10 years is necessary.

PMID- 15720992
TI  - Internal packing in the control of hemorrhage from large retroperitoneal veins.
AB  - BACKGROUND: Hemorrhage from large retroperitoneal veins is usually controlled by
      suturing the venous tear. Infrequently, the extent and location of the tear and
      amount of hemorrhage preclude successful suturing. METHODS: In seven patients
      with severe hemorrhage from large retroperitoneal veins encountered in
      association with resection of retroperitoneal sarcoma (6) or repair of a ruptured
      abdominal aortic aneurysm (1), packing of the area with sufficient amounts of
      Surgicel (Ethicon, Johnson & Johnson, Somerville, NJ) and pressure for one half
      hour was used. RESULTS: All seven patients did not show any bleeding
      postoperatively and no clinical sequelae developed, with the exception of one
      patient who developed an abscess requiring drainage. CONCLUSION: Internal packing
      with Surgicel appears to be reliable in controlling venous hemorrhage not
      manageable by the standard methods and may be preferable to roll gauze packing.

PMID- 15720993
TI  - Operative therapy for cecal volvulus combining resection with colopexy.
AB  - BACKGROUND: Cecal volvulus is an uncommon clinical event. The literature contains
      many recommended treatments with varied results. STUDY DESIGN: A series of 10
      consecutive patients treated by the author was reviewed. Each patient had
      complete clinical follow-up. The cecal volvulus was resected without detorsion
      and reperfusion of the volvulus. The intestine was resected using a surgical
      stapling device, transection of the mesentery at the axial twist, and a stapled
      anastomosis of the terminal ileum to the remnant of the right colon. Permanent
      sutures between the colonic tenia and the peritoneum of the right paracolic
      gutter fixed the remainder of the right colon to prevent recurrence of the
      volvulus. RESULTS: The author in clinical practice surgically treated a series of
      10 consecutive patients with complete follow-up between 1981 to 2004. All
      patients survived the surgical procedure and were discharged from the hospital.
      The diagnosis was determined preoperatively in 5 of the 10 patients. Five
      patients had gangrene of the colon, and two of these patients had perforation.
      All patients required postoperative intensive care from 2 to 9 days. Five of the
      10 patients required ventilator support for 1 to 3 days. Postoperative
      complications included intraperitoneal bleeding, pneumonia, and surgical incision
      infection with a subcutaneous abscess. There has been no recurrence of the
      volvulus in any of these patients. CONCLUSIONS: Ten consecutive cases of cecal
      volvulus were surgically treated by a uniform resection procedure. The cecal
      volvulus was not reperfused by detorsion. Reperfusion of ischemic or gangrenous
      bowel can possibly produce reperfusion injury, metabolic acidosis, intestinal
      bacterial, and toxin translocation with possible irreversible septic shock.
      Recurrence of the cecal volvulus was prevented by colopexy of the right colon
      remnant. Avoidance of reperfusion of the cecal volvulus with resection, primary
      anastomosis, and colopexy resulted in successful results in a small series in
      clinical practice.

PMID- 15720994
TI  - Risk factors for the intermediate outcome of morbid obesity after
      laparoscopically placed adjustable gastric banding.
AB  - BACKGROUND: The overall long-term results of medical treatment for morbid obesity
      are poor. Surgery is the only treatment option to obtain long-term weight
      reduction. Analysis of risk factors for treatment success of laparoscopically
      placed gastric banding (LGB) has not been available until now. METHODS:
      Prospective study with 99 patients with LGB between January 1997 and July 2003.
      The parameters assessed as risk factors included onset of obesity, feeling of
      postprandial satiety, and initial body mass index (BMI). RESULTS: Median follow
      up was 36 months (3 to 72). Independent prognostic factors of excess body weight
      reduction (>25%) were for the first postoperative year: onset of obesity as an
      adolescent (relative risk [RR] 0.21), an initial BMI <45 kg/m(2) (RR 4.76), and a
      BMI between 45.1 and 50 kg/m(2) (RR 3.23). After the second year, independent
      prognostic factors were as follows: feeling of postprandial satiety (RR 5.26) and
      an initial BMI <45 kg/m(2) (RR 3.03). CONCLUSION: LGB is suitable to achieve
      intermediate weight reduction in patients with morbid obesity. To obtain the best
      results, patients should be treated before they achieve a BMI >45 kg/m(2).
      Additionally a postprandial feeling of satiety after LGB is mandatory for good
      long-term results.

PMID- 15720995
TI  - A comparison of the Ranson, Glasgow, and APACHE II scoring systems to a multiple
      organ system score in predicting patient outcome in pancreatitis.
AB  - BACKGROUND: Systems for evaluating acute pancreatitis are useful in hospitalized
      patients. Traditional systems of evaluation are well established but might be
      outdated. We propose a Multiple Organ System Score (MOSS) containing data that
      are more consistently collected and which are accurate in predicting patient
      outcome. METHODS: A retrospective chart review of 49 patients was completed. We
      determined if the physician obtained all of the variables necessary to calculate
      Ranson, Glasgow, or APACHE II scores, if these scores were predictive of patient
      outcome in the form of length of hospital stay (LOS), and if new, more frequently
      evaluated variables could be used. RESULTS: None of the patients could be
      assigned complete scores. According to Spearman rank correlation, both Glasgow
      and MOSS showed correlation with patient outcome when APACHE II and Ranson did
      not. CONCLUSIONS: Although larger studies should be performed, the MOSS is useful
      in predicting outcomes of patients with acute pancreatitis.

PMID- 15720996
TI  - Nonstandard pancreatic resections for unusual lesions.
AB  - BACKGROUND: Pancreatic resections including pancreaticoduodenectomy and distal
      pancreatectomy are the standard of care for patients with malignant tumors of the
      pancreas. Patients with benign disease or unusual tumors may benefit from other
      nonstandard resections. METHODS: A review of the literature and the author's
      experiences were undertaken. RESULTS: Parenchymal-sparing surgeries including
      pancreatic enucleation, central pancreatectomy, splenic-preserving distal
      pancreatectomy, and duodenal-preserving pancreatic head resection are described.
      The utility of each procedure is reviewed. Outcome results from published series
      are included. CONCLUSIONS: Nonstandard pancreatic resections should be considered
      in select patients with unusual lesions. Such procedures are safe and effective
      and may be associated with a reduced incidence of exocrine insufficiency.

PMID- 15720997
TI  - Locally recurrent breast cancer after conservation therapy.
AB  - BACKGROUND: Today, the majority of small invasive and noninvasive breast cancers
      are treated with breast conservation therapy (BCT). The incidence of local
      regional recurrence (LRR) after BCT for stage 0, I, and II patients ranges
      between 5% and 22%. METHODS: A literature search for BCT, local recurrence, and
      regional recurrence was performed. Data from over 50 articles pertaining to the
      characteristics, risk factors, detection, management, and prognosis of these
      patients with LRR after BCT were collected and analyzed. RESULTS: Positive
      margins, high-grade ductal carcinoma in situ (DCIS), young age, and the absence
      of radiation therapy after BCT increase the risk for LRR. Prognosis at LRR is
      impacted by invasive versus noninvasive histology, size and stage, method of
      detection, and involvement of skin and/or axillary lymph nodes. The standard
      treatment is salvage mastectomy. CONCLUSIONS: The prognosis for LRR after BCT is
      favorable compared with patients with postmastectomy chest wall recurrence.

PMID- 15720998
TI  - A comparison of the adverse reactions associated with isosulfan blue versus
      methylene blue dye in sentinel lymph node biopsy for breast cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is an established means of staging
      the axilla in patients with breast cancer. Recently, methylene blue dye has been
      shown to be an efficacious and cost-effective alternative to isosulfan blue. With
      the increasing popularity of SLNB, the potential complications of isosulfan blue
      use must be appreciated. METHODS: A literature search for English language
      articles available on MEDLINE from 1985 to November 2002 using the search terms
      allergy, allergic reaction, anaphylactic reactions, anaphylaxis, blue dye, breast
      cancer, isosulfan blue, methylene blue, and sentinel lymph node biopsy identified
      24 reports. CONCLUSIONS: The use of isosulfan blue due for SLNB is associated
      with a significant number of allergic reactions, some of which are life
      threatening. Because methylene blue dye has been shown to be equally effective
      and does not pose a serious risk of serious allergic reactions, it offers an
      improved technique above isosulfan blue dye for SLNB.

PMID- 15720999
TI  - Usefulness of a single trocar for intrathoracic anastomosis during open thoracic
      surgery for esophageal cancer.
AB  - When patients with esophageal cancer undergo intrathoracic anastomosis after
      esophagectomy in our institution, we resect the lesser curvature in the thorax
      using a surgical instrument after circular-stapled esophagogastric anastomosis.
      We then place the trocar in the seventh intercostal space on the midaxillary
      line, except in fifth intercostal anterolateral thoracotomy. A linear stapler
      applied through the thoracotomy sometimes blocks the operator's view, and so it
      is not so easy to operate with a rather big head in the thorax. We operate a
      linear cutter for laparoscopic surgery through the trocar. With this method, the
      instrument is used in good position in respect to the operator's view, and access
      to the gastric tube is easy. Moreover, we can adjust the resectional angle with
      this instrument by using the bending mechanism in its shaft. Furthermore, we can
      reuse the trocar site for the chest tube.

PMID- 15721000
TI  - Didactic lecture versus instructional standardized patient interaction in the
      surgical clerkship.
AB  - BACKGROUND: Medical schools increasingly employ the standardized patient
      interaction (SPI) as a teaching and testing modality to prepare students for
      USMLE Step 2 Clinical Skills (Step 2 CS). However, little is known about the
      perceptions medical students have toward SPIs. We hypothesized that the SPI would
      increase the self-confidence of surgery students in their history and physical
      examination (H&P) skills as compared with the classic lecture format and that
      students would perceive the SPI as a valuable learning tool. METHODS: Students (n
      = 126) on the junior surgery clerkship were randomized into two groups. Group A
      (n = 61) received a didactic lecture on acute appendicitis. Group B (n = 65)
      participated in an SPI in which the portrayed patient had acute appendicitis.
      Student perceptions were surveyed by written questionnaire pre- and postencounter
      using a 5-point Likert scale, with 5 being the most favorable rating. Data
      (perceptions, performances on the SPI, clerkship grades) were compared using a
      Student t test followed by the Mann-Whitney rank sums test. RESULTS: Group A
      "enjoyed" the lecture format more than group B "enjoyed" the SPI format (3.4 +/-
      0.1 versus 2.6 +/- 0.1, P <.001) and perceived the lecture as having more value
      to their overall education (3.5 +/- 0.1 versus 2.6 +/- 0.1, P <.001) than the SPI
      group. Surprisingly, student self-confidence in their H&P skills increased after
      the didactic lecture (from 3.6 +/- 0.1 to 4.1 +/- 0.1, P = .001) but not after
      the SPI (from 3.6 +/- 0.1 to 3.8 +/- 0.1, P = not significant). CONCLUSIONS: The
      didactic lecture format was not only enjoyed and valued more than the SPI, but
      our surgery students also perceived it as superior to the SPI in building
      confidence in history and physical examination skills. These findings suggest
      that surgical educators should develop ways to improve students' perceptions and
      attitudes surrounding the surgical SPI.

PMID- 15721001
TI  - Colonic T-cell leukemia mimicking colon carcinoma.

PMID- 15721002
TI  - Sentinel lymph node biopsy followed by delayed mastectomy and reconstruction.

PMID- 15721003
TI  - A new repair for midline ventral hernias using a Kugel mesh.

PMID- 15721004
TI  - What causes acute coronary syndromes? Applying Koch's postulates.
AB  - The term "acute coronary syndromes" (ACS) is used to describe a heterogeneous
      spectrum of clinical conditions. This includes myocardial infarction, non-ST
      elevation myocardial infarction, and unstable angina. These conditions are linked
      by a similar constellation of signs and symptoms but not necessarily by a common
      pathophysiology. They are syndromes. Several different hypotheses exist that have
      attempted to explain the pathological mechanisms that are involved in these
      conditions, however, it is not clear whether ACS are caused by variations of a
      single disease process or by several disease processes. The contribution of both
      vessel wall- and blood-related factors in the pathogenesis of acute coronary
      syndromes is herein discussed with the guidance of Koch's postulates.

PMID- 15721005
TI  - Very low density lipoproteins provide a vector for secretion of paraoxonase-1
      from cells.
AB  - Paraoxonase-1 (PON1) requires a suitable acceptor complex for its secretion from
      producing cells. The serum lipoprotein, high-density lipoprotein (HDL) has been
      shown to accomplish this function, whereas low-density lipoproteins are
      ineffective. The present study examined the influence of the third serum
      lipoprotein subclass, very low density lipoproteins (VLDL), on PON1 secretion.
      VLDL were shown to promote secretion of PON1 from a transfected Chinese hamster
      ovary model and from transfected hepatocytes in a high-affinity, saturable
      manner. The effects of HDL and VLDL were not additive, suggesting that they may
      employ a common secretion pathway. VLDL was able to stabilise secreted PON1
      enzyme activity, but less effectively than stabilisation by HDL. Following co
      incubation of VLDL and HDL, the majority of PON1 accumulated in HDL even if HDL
      was added after initial association of the enzyme with VLDL. VLDL to HDL transfer
      of PON1 was rapid and did not require lipolysis of VLDL. Low levels of active
      PON1 were associated with VLDL in human serum, and VLDL-associated enzyme
      activity was proportional to serum triglyceride concentrations. Serum
      triglycerides were positively associated with whole serum PON1 mass but
      negatively associated with specific activity. PON1-enriched VLDL was more
      resistant to oxidation in vitro. The present study suggests that the triglyceride
      transport vector, VLDL, can modulate PON1 metabolism and activity. This is due,
      in part, to an influence of the lipoprotein on PON1 secretion. PON1 was
      associated with VLDL in human serum, where triglycerides correlated independently
      with variations in serum mass and activity of the enzyme. VLDL-associated PON1
      exerted an anti-oxidative effect, which may be of physiological benefit.

PMID- 15721006
TI  - Intravascular adenovirus-mediated lipoprotein-associated phospholipase A2 gene
      transfer reduces neointima formation in balloon-denuded rabbit aorta.
AB  - Postangioplasty restenosis is a multifactorial process and involves mechanisms
      such as inflammation and stimulation of the expression of growth factors.
      Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) can modify inflammatory
      responses by hydrolyzing phospholipids with shortened and/or oxidized sn-2
      residues. In this study, we tested a hypothesis that adenovirus-mediated Lp
      PLA(2) gene transfer can reduce restenosis in rabbits. Aortas of cholesterol-fed
      NZW rabbits were balloon-denuded and intra-arterial gene transfer was performed
      using Dispatch catheter with Lp-PLA(2) or LacZ adenoviruses (1.15 x 10(10)pfu).
      Intima/media ratio (I/M), histology and cell proliferation were analyzed. Two
      weeks after the gene transfer I/M in the LacZ-transduced control group was 0.45+/
      0.05 but Lp-PLA(2) gene transfer reduced I/M to 0.25+/-0.03. At four weeks time
      point I/M in the Lp-PLA(2) group (0.34+/-0.05) was also lower than in the LacZ
      group (0.53+/-0.06). Plasma Lp-PLA(2) activity was increased in the Lp-PLA(2)
      group (48.2+/-4.2) as compared to the LacZ group (33.6+/-3.51) at two weeks time
      point. Transgene expression was detected in the arterial wall two and four weeks
      after the procedure. Apoptosis was higher in the control vessels than in the Lp
      PLA(2) group at two weeks time point. In conclusion, local adenovirus-mediated Lp
      PLA(2) gene transfer resulted in a significant reduction in neointima formation
      in balloon-denuded rabbit aorta and may be useful for the prevention of
      restenosis after arterial manipulations.

PMID- 15721007
TI  - Confocal scanning laser microscopy measurements of atherosclerotic lesions in
      mice aorta. A fast evaluation method for volume determinations.
AB  - Atherosclerotic lesion size in mice is routinely evaluated by morphometrical
      measurements on serial sections in order to obtain volume measurements. The
      technique of confocal scanning laser microscopy (CSLM) makes it possible to
      optically scan and thereby evaluate a tissue sample. We here describe a method
      for measuring lesion volume in ApoE/LDLr deficient mice at 20 and 30 weeks of age
      using the non-destructive procedure of CSLM. Whole mount preparations of opened
      aorta with the lumen side facing the cover slip were analysed under 10x
      magnification in a CSLM (Leica). The autofluorescence of the elastic fibres of
      the lamina interna as opposed to the non-fluorescing lesion was used to define
      the bottom and top of the lesion during scanning. Ten to forty images were
      collected 2.4 microm apart, depending on the size of the lesion, and the stack of
      images was then analysed using Imaris (Bitplane). After the CSLM evaluation, the
      aortas were de-mounted, embedded in paraffin, sectioned, stained in hematoxylin
      and eosin and the volume re-evaluated with conventional morphometry. Statistical
      evaluation showed that the results obtained with CSLM and the results of
      morphometry were positively correlated. Area measurements of the plaques using en
      face preparations of aorta showed that the plaque area was generally larger at
      the left side and a significant increase of plaque area along the length of the
      thoracic aorta. Our results showed that atherosclerotic lesions in mice can be
      quantitatively evaluated by CSLM.

PMID- 15721008
TI  - Involvement of oxidative stress and NADPH oxidase activation in the development
      of cardiovascular complications in a model of insulin resistance, the fructose
      fed rat.
AB  - Growing evidences suggest a role of oxidative stress in hypertension and cardiac
      hypertrophy. The fructose (60%)-fed rat represents a model of metabolic syndrome,
      associating insulin resistance and high blood pressure. In this model,
      hypertension, cardiac and vessels hypertrophy and markers of oxidative stress
      were determined. In addition, the production of reactive oxygen species (ROS) was
      evaluated at different times after the initiation of fructose-enriched diet in
      aorta, heart and polymorphonuclear cells. High fructose feeding was associated
      with an early (1-week) increase in ROS production by aorta, heart and circulatory
      polymorphonuclear cells, in association with enhanced markers of oxidative
      stress. Vascular and cardiac hypertrophy was also rapidly observed, while the
      rise in blood pressure was significant only after 3 weeks. In summary, our study
      suggests that the production of reactive oxygen species can be a key-event in the
      initiation and development of cardiovascular complications associated with
      insulin resistance.

PMID- 15721009
TI  - TNFalpha increases the inflammatory response to vascular balloon injury without
      accelerating neointimal formation.
AB  - There is now clear evidence for a contributory role of inflammatory processes to
      restenosis following vascular balloon injury and stent implantation. The aim of
      the present study was to study the effects of TNFalpha, administered locally in
      vivo immediately following balloon angioplasty, on the leukocyte adhesive
      response and extent of neointimal formation in a rabbit model of subclavian
      artery injury. Initial in vitro studies were performed with normal isolated
      artery rings to assess the vascular adhesive response to TNFalpha or IL-1beta.
      Pre-incubation with either cytokine prior to addition of (51)Cr-labelled
      leukocytes enhanced the adhesion of leukocytes to the artery in both a time- and
      concentration-dependent manner. Although both cytokines induced an increase in
      the expression of the adhesion molecules ICAM-1 and VCAM-1, only antibodies to
      ICAM-1 blocked the enhanced adhesion induced by the cytokines. In artery segments
      retrieved from rabbits that had previously undergone subclavian artery
      angioplasty either 24 h or 8 days previously, there was an injury-induced
      increase in adhesion of leukocytes assessed ex vivo. In segments obtained from
      rabbits that received a 15 min local infusion of TNFalpha (2 ng/min) to the
      injured artery immediately after the angioplasty procedure, leukocyte adhesion
      assessed ex vivo was further significantly enhanced. The pro-adhesive effect of
      TNFalpha was associated with an increased expression of both ICAM-1 and VCAM-1.
      However, TNFalpha administration did not alter the extent of neointimal formation
      observed 8 days after injury. These findings suggest that while TNFalpha may play
      a role following vascular injury, it does not act alone to induce neointimal
      formation. Thus anti-inflammatory strategies targeted at multiple cytokines may
      be more appropriate than targeting a single cytokine to reduce the response to
      vascular injury.

PMID- 15721010
TI  - Sterol-regulatory-element binding protein inhibits upstream stimulatory factor
      stimulated hepatic lipase gene expression.
AB  - Hepatic lipase (HL) not only plays an important role in plasma lipoprotein
      transport, but may also affect intracellular lipid metabolism. We hypothesize
      that HL expression is regulated as an integral part of intracellular lipid
      homeostasis. Addition of oleate (1 mM) to HepG2 cells increased HL secretion to
      134+/-14% of control (p<0.02), and increased the transcriptional activity of a
      698-bp HL promoter-reporter construct two-fold. Atorvastatin (10 microM)
      abolished the oleate stimulation. The transcriptional activity of a sterol
      regulatory-element binding protein (SREBP)-sensitive HMG-CoA synthase promoter
      construct was reduced 50% by oleate, and increased 2-3-fold by atorvastatin. Co
      transfection with an SREBP-2 expression vector reduced HL promoter activity and
      increased HMG-CoA synthase promoter activity. Upstream stimulatory factors (USF)
      are also implicated in maintenance of lipid homeostasis. Co-transfection with a
      USF-1 expression vector stimulated HL promoter activity 4-6-fold. The USF
      stimulated HL promoter activity was not further enhanced by oleate, but almost
      completely prevented by atorvastatin or co-transfection with the SREBP-2 vector.
      Opposite regulation by USF-1 and SREBP-2 was also observed with a 318-bp HL
      promoter construct that lacks potential SRE-like and E-box binding motifs. We
      conclude that the opposite regulation of HL expression by fatty acids and statins
      is mediated via SREBP, possibly through interaction with USF.

PMID- 15721011
TI  - Paraoxonase 1 (PON1) enhances HDL-mediated macrophage cholesterol efflux via the
      ABCA1 transporter in association with increased HDL binding to the cells: a
      possible role for lysophosphatidylcholine.
AB  - We investigated the role of HDL-associated paraoxonase 1 (PON1) in HDL-mediated
      macrophage cholesterol efflux by using HDL derived from wild type mice (Control
      HDL), from human PON1-transgenic mice (HDL-PON1Tg) or from PON1-knockout mice
      (HDL-PON1(0)). Cholesterol efflux from mouse peritoneal macrophages (MPM) or from
      J774 A.1 macrophage cell line by HDL-PON1Tg, was significantly increased (by 60%)
      compared to HDL-PON1(0). We demonstrated that this PON1 effect was associated
      with an increased HDL binding to the cells, as the binding of HDL-PON1Tg (or HDL
      PON1(0) that was enriched with PON1) was increased by 50% compared to that of HDL
      PON1(0). Using either a cAMP analogue, to increase ABCA1 receptor expression, or
      rabbit anti-mouse SR-BI specific antibody to block the SR-BI receptor, PON1
      stimulation of HDL binding and of HDL-mediated macrophage cholesterol efflux,
      were both found to involve the ABCA1 transporter. Studies with PON1 specific
      inhibitors revealed that PON1 activity was required for its stimulation of HDL
      mediated macrophage cholesterol efflux. Upon incubation of macrophages with
      Control-HDL or with HDL-PON1Tg, macrophage lysophosphatidylcholine (LPC) content
      was increased by 3.7- and 7.5-fold, respectively. Such an LPC enrichment of
      macrophages resulted in up to 60% increased HDL binding to the cells, and a 41%
      increased HDL-mediated cholesterol efflux. Similarly, macrophage loading with LPC
      (by either adding LPC, or PON1 or phospholipase A(2)) significantly increased
      apolipoprotein A-I (apoA-I) mediated cholesterol efflux by 104, 65 and 56%,
      respectively, in ABCA1 overexpressing macrophages. We conclude that HDL
      associated PON1 may contribute to the attenuation of atherosclerosis development
      by its ability to act on macrophage phospholipids, to form LPC, in turn,
      stimulates HDL binding and HDL-mediated macrophage cholesterol efflux via the
      ABCA1 transporter.

PMID- 15721012
TI  - The effect of heparin on osteoblast differentiation and activity in primary
      cultures of bovine aortic smooth muscle cells.
AB  - Recent studies have suggested that aortic smooth muscle cells undergo a
      phenotypic transition into osteoblast-like cells and mineralize when cultured in
      the presence of beta-glycerophosphate. Since we had previously demonstrated that
      heparin could inhibit osteoblast differentiation and mineralization in primary
      cultures of murine calvaria cells, we were interested in determining if heparin
      would have a similar effect when primary aortic smooth muscle cells were cultured
      in the presence of beta-glycerophosphate. The effect of heparin and low molecular
      weight heparin (LMWH) on osteoblast differentiation and activity was therefore
      examined in primary cultures of bovine aortic smooth muscle cells (BASMC) over a
      14-day period. Here, we report that BASMC differentiate into osteoblast-like
      cells when cultured in the presence of beta-glycerophosphate. Moreover, we report
      that heparin not only inhibits this process but that it also inhibits the ability
      of BASMC to mineralize as well. Importantly, these effects were found not to be
      dependent upon heparins' anticoagulant activity since unfractionated heparin and
      heparins with low anti-thrombin III affinities inhibited the mineralization
      process equally well. Sulfation, however, was found to be a major determinant of
      heparins ability to inhibit BASMC mineralization since neither dermatan sulfate
      nor N-desulfated heparin were able to demonstrate an effect. We conclude that
      BASMC cultures can undergo a phenotypic transition into mature osteoblasts and
      that both the differentiation process and their ability to mineralize are
      inhibited by heparin.

PMID- 15721013
TI  - Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in
      cholesterol-fed Tg rabbits.
AB  - Lipoprotein lipase (LPL) produced by macrophages is upregulated in the
      atherosclerotic lesions; however, it is not fully understood whether increased
      macrophage-derived LPL is pro-atherogenic. To examine the hypothesis that
      macrophage-derived LPL in the arterial wall enhances atherosclerotic lesion
      formation, we generated transgenic (Tg) rabbits that express the human LPL
      transgene under the control of the human scavenger receptor enhancer/promoter,
      which drives macrophage-specific expression of the human LPL gene. We fed Tg and
      non-Tg littermate rabbits a diet containing 0.3% cholesterol for 16 weeks and
      compared their lipoproteins and aortic atherosclerosis. We found that there was
      no difference in plasma lipid or lipoprotein profiles between Tg and non-Tg
      rabbits; however, atherosclerotic lesions were significantly increased in Tg
      compared to non-Tg rabbits. There was a 1.4-fold increase in total aortic en face
      lesions and a 2-fold increase in intimal lesions evaluated by image analysis
      system. Furthermore, immunohistochemical staining revealed that the increased
      atherosclerotic lesions present in Tg rabbits were characterized by marked
      accumulation of macrophage-derived foam cells and frequently associated with the
      deposition of oxidized LDL. These results support the notion that macrophage
      derived LPL in the arterial wall is pro-atherogenic, possibly via the enhancement
      of foam cell formation during atherogenesis.

PMID- 15721014
TI  - Edaravone, a novel radical scavenger, inhibits oxidative modification of low
      density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the
      expression of endothelial nitric oxide synthase.
AB  - Edaravone, a newly synthesized synthetic radical scavenger, has been identified
      and adopted as an anti-stroke agent. However, its mechanism and the effect of
      edaravone on lipoprotein oxidation are not fully understood. Therefore, whether
      edaravone could suppress oxidation of low-density lipoprotein (LDL) and be
      involved in the expression of endothelial nitric oxide synthase (eNOS) in
      relation to anti-atherogenesis by improving and conserving vascular circulation
      was investigated. We investigated the in vitro effects of edaravone on copper-
      and endothelial cell-mediated LDL oxidation, and the expression of eNOS in human
      umbilical vein endothelial cells (HUVEC) modulated by oxidized LDL. The in vivo
      effect of edaravone on antioxidative effect was also studied in male rats
      intravenously administered with edaravone. Edaravone apparently inhibited copper-
      and HUVEC-mediated LDL oxidation at the concentration equivalent to serum
      concentrations in clinical use. The intravenous administration of edaravone also
      enhanced serum radical-scavenging property in rats. We tested the effect of
      edaravone on protein and mRNA expression of eNOS in HUVEC. Edaravone enhanced
      eNOS expression in HUVEC, presumably because of increased stability of eNOS mRNA,
      and reversed eNOS expression reduced by oxidized LDL nearly to the control
      levels. The present study demonstrates for the first time that edaravone
      increases eNOS expression with the inhibition of LDL oxidation, and that
      edaravone can reverse oxidized LDL-mediated reduction in eNOS expression in
      endothelial cells. The preventive action of edaravone from ischemic disease
      consequence may be attributed to these eNOS up-regulation with decreased
      oxidation.

PMID- 15721015
TI  - Progression of peripheral arterial occlusive disease is associated with Chlamydia
      pneumoniae seropositivity and can be inhibited by antibiotic treatment.
AB  - A possible influence of Chlamydia pneumoniae seropositivity on the clinical
      course of peripheral arterial occlusive disease (PAOD) has not been investigated
      previously. Though roxithromycin therapy was found to inhibit progression of
      PAOD, the nature of this effect (antibiotic or anti-inflammatory) has remained
      elusive. The course of PAOD was prospectively assessed in elderly men during 4
      years, comparing 51 C. pneumoniae seropositive (IgG>/=1:128) with 46 seronegative
      patients (IgG<1:64 and IgA<1:32). Twenty of the seropositive patients were
      treated with roxithromycin (400 mg daily) for 4 weeks. Limitation of the walking
      distance to 200 m or less was observed in 55% of the seropositive untreated
      patients as compared to 30% of both, seronegative and macrolide-treated patients.
      The number of invasive revascularizations per patient was 1.7 in the seropositive
      untreated group as compared to 0.5 in the seronegative and the macrolide-treated
      group. Considering possible confounding variables, such as classical vascular
      risk factors, ordinal regression analyses showed a significant association of C.
      pneumoniae seropositivity with limitation of the walking distance (p=0.027) and
      need for invasive revascularization (p=0.037). The effect of macrolide treatment
      on these outcome measures was marked (p<0.001 and p=0.040, respectively) during
      2.7 years but decreased in the second part of the observation period. This study
      provides good evidence that C. pneumoniae are involved in the progression of PAOD
      and that antibiotic treatment directed against C. pneumoniae is effective in
      inhibiting this process.

PMID- 15721016
TI  - Correlation of parents' longevity with carotid intima-media thickness in patients
      attending a Lipid Clinic.
AB  - The relationship between carotid intima-media thickness (IMT) and the subject's
      parents' longevity has been investigated. The association between parents' age at
      death and IMT was estimated in 593 consecutive patients attending a Lipid Clinic
      by survival-analysis methods. Average maximum IMT (Avg-IMT), maximum IMT (Max
      IMT), clinical and laboratory variables and parental age at death, were assessed.
      Kaplan-Meier analyses showed significant differences in survival curves, low IMTs
      being associated with long-lived parents (p=0.0003 and 0.001 by log-rank test for
      fathers and mothers, respectively). A Cox proportional hazards regression model
      showed that higher carotid IMT values were associated with father's and mother's
      deaths at an early age, even after adjusting for conventional cardiovascular risk
      factors. These data were confirmed after the stratification of patients into
      younger (<65 y) and older (>/=65 y) or into subjects with and without a family
      history of dyslipidemia or vascular diseases. In addition, by stratifying
      subjects into those with no, one or two long-lived parents, we observed a
      significant trend for the combination of father's and mother's longevity on their
      offspring's IMTs (p<0.01 and 0.05 for Avg-IMT and Max-IMT, respectively). These
      data highlight a significant relationship between carotid artery IMT and a
      familial predisposition to be long-lived that is independent of the individual's
      vascular risk profile.

PMID- 15721017
TI  - Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels
      on chromosome 21q.
AB  - High levels of low-density lipoprotein (LDL) cholesterol, low levels of high
      density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are
      strong predictors of cardiovascular disease risk. Motivated by previous evidence
      for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage
      analysis of LDL cholesterol and TG concentration among participants of the
      Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the
      NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive
      siblings and their first-degree relatives were recruited. Both phenotypes were
      similarly adjusted for ethnicity, study center, sex, age, age-by-sex
      interactions, smoking, alcohol consumption, hormone use, diabetes medication use,
      and waist circumference. Variance component linkage analysis was performed as
      implemented in SOLAR, using ethnicity-specific marker allele frequencies derived
      from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide
      empirical LOD score of 3.9 was detected on chromosome 21 at 54cM, between markers
      D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant
      linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three
      other studies and is suggestive of one or more genes on chromosome 21q jointly
      regulating LDL cholesterol and TG concentration.

PMID- 15721018
TI  - Association of CagA+ Helicobacter pylori infection with aortic atheroma.
AB  - BACKGROUND: To investigate possible association between infection with CagA(+)
      strains of Helicobacter pylori and aortic atheroma diagnosed by transesophageal
      echocardiography. METHODS AND RESULTS: One hundred and eighty-eight consecutive
      subjects prospectively examined for presence of aortic atheroma (localized
      intimal thickening of >/=3mm) by transesophageal echocardiography were tested for
      serum IgG antibodies against H. pylori (enzyme-linked immunosorbent assay) and
      CagA protein (Western blot assay). The association between infection with H.
      pylori, CagA status of the infecting H. pylori strains, and aortic
      atherosclerosis was evaluated after adjusting for coronary artery disease risk
      factors. There was a linear trend for presence of atheroma in subjects with CagA
      positive H. pylori infection (51/81, 63%) compared to subjects with CagA-negative
      H. pylori infection (21/45, 46.7%) and uninfected subjects (18/62, 29%)
      (p=0.003). H. pylori seropositivity was not associated with aortic atheroma (OR
      2.9; 95% CI, 0.8-10.3; p=0.11) when CagA status is not taken into account. On
      multivariate analysis, parameters associated with risk of aortic atheroma were
      CagA-positive H. pylori seropositivity (OR 4.4; 95% CI, 1.4-14.7; p=0.01), older
      age (OR 1.2; 95% CI, 0.9-14.7; p=0.01), having ever smoked cigarettes (OR 3.6;
      95% CI, 1.3-10.0; p<0.001), and elevated serum triglyceride level (OR 3.4; 95%
      CI, 1.3-9.4; p=0.02). CONCLUSIONS: After controlling for H. pylori infection and
      coronary artery disease risk factors, infection with a CagA-positive strain of H.
      pylori was independently associated with aortic atherosclerosis. This study
      suggests a gradient of atherosclerosis between uninfected individuals and
      patients with CagA-positive H. pylori infection and should prompt research into
      the role of CagA-positive H. pylori infection in the inflammatory atherosclerotic
      process.

PMID- 15721019
TI  - Cytomegalovirus infection is associated with elevated interleukin-10 in coronary
      artery disease.
AB  - Previous studies show that cytomegalovirus (CMV) infection could increase the
      production of inflammatory cytokines in coronary artery disease (CAD). However,
      little is known about the influence of CMV infection on interleukin-10 (IL-10)
      levels in CAD. We attempted to investigate the relationships between CMV
      infection and serum IL-10 levels in patients with CAD. CMV IgG and serum levels
      of IL-10 were measured with ELISA in patients with CAD (n=463) and smooth
      coronary artery controls documented by coronary arteriography (n=125). Subjects
      were dichotomized according to calculated median level of IL-10 (6.84 pg/ml) in
      different groups or subgroups. The seropositivity of CMV IgG was more frequently
      found in the high IL-10 group than the low IL-10 group (46.8% versus 30.4%,
      P<0.001). The prevalence of CMV infection was significantly higher in the high IL
      10 group than the low IL-10 group among the patients with CAD (48.1% versus
      28.6%, P<0.001), but among the controls (40.4% versus 35.6%, P=0.588). On
      multiple logistic regression analysis, the adjusted odds ratio (95% confidence
      intervals) of high IL-10 associated with CMV infection was 2.3 (1.6-3.4, P<0.001)
      in the patients with CAD, and 1.1 (0.5-2.5, P=0.83) in the controls. We found a
      significant association of CMV infection with elevated IL-10 in the patients with
      CAD; therefore, we propose that changes in the immune response to CMV are a
      compounding factor in CAD.

PMID- 15721020
TI  - Circulating malondialdehyde-modified LDL and atherogenic lipoprotein profiles
      measured by nuclear magnetic resonance spectroscopy in patients with coronary
      artery disease.
AB  - OBJECTIVE: Recent studies have suggested that circulating malondialdehyde
      modified low-density lipoprotein (MDA-LDL) is a useful marker for the
      identification of patients with coronary artery disease (CAD). However, the role
      of MDA-LDL in atherogenic mechanisms has not yet been fully determined. METHOD
      AND RESULTS: We investigated lipoprotein profiles measured by nuclear magnetic
      resonance (NMR) spectroscopy and circulating MDA-LDL levels measured by ELISA in
      25 male patients with CAD and 15 age-matched male controls. We selected subjects
      who had a serum LDL cholesterol<160 mg/dL. The MDA-LDL levels were significantly
      higher in the CAD group than in the control group (P=0.01) even though there was
      no significant difference in the LDL cholesterol levels between the two groups.
      NMR analysis demonstrated that the MDA-LDL levels were positively correlated with
      large and intermediate very low-density lipoprotein triglyceride and LDL particle
      concentrations, and negatively correlated with LDL diameter and large high
      density lipoprotein cholesterol. The MDA-LDL levels were negatively correlated
      with flow-mediated dilatation of the brachial artery. CONCLUSIONS: The high
      concentrations of circulating MDA-LDL derived from the atherogenic lipoprotein
      profiles, which induce the exaggerated production of small dense LDL. The
      circulating MDA-LDL may impair endothelial function and play an important role in
      the pathogenesis of atherosclerosis.

PMID- 15721021
TI  - Ex vivo measures of LDL oxidative susceptibility predict carotid artery disease.
AB  - AIM: The purpose of the study was to assess whether ex vivo measures of low
      density lipoprotein (LDL) oxidation improved prediction of carotid artery disease
      (CAAD) case-control status compared to standard lipid and smoking measures.
      METHODS: One hundred and forty cases with a high degree of carotid artery
      stenosis aged 40-83 years and an equal number of controls without stenosis or
      other vascular disease were matched by censored age within 2 years. Matched
      logistic regression evaluated the significance of copper-induced oxidative
      measures with and without covariates. The relationship of LDL oxidation measures
      with statin use and current smoking was also evaluated. RESULTS: Logistic
      regression demonstrated a significant effect of the three correlated measures of
      oxidative susceptibility (lag time, oxidation rate and maximal rate of oxidation)
      separately on disease prediction (all p<0.05). These oxidative measures remained
      significant predictors of case-control status when other cardiovascular disease
      predictors (age; LDL-C, HDL-C and ApoAI levels; current smoking, ever smoking and
      pack-years smoked) were jointly considered. This relationship was not
      attributable to the effects of statin use on LDL oxidation. CONCLUSIONS: Ex vivo
      measures of oxidation improved the prediction of carotid artery disease status,
      suggesting that this is an important determinant of atherosclerotic risk in this
      older population.

PMID- 15721022
TI  - Associations of soluble intercellular adhesion molecule-1 with carotid
      atherosclerosis progression.
AB  - Our previous study demonstrated that plasma concentration of high-sensitivity C
      reactive protein (hs-CRP) is a marker of carotid atherosclerosis activity. In
      this study, we investigated whether plasma levels of soluble cell adhesion
      molecules have potential value to predict atherosclerosis progression. The study
      included 192 outpatients 40-82 years of age who were treated for traditional risk
      factor for cardiovascular disease. Patients underwent repeated ultrasonographic
      evaluation for 53+/-11 months. Severity of atherosclerosis was evaluated by the
      maximal intimal-medial thickness (max-IMT), plaque number (PN) and plaque score
      (PS, the sum of all plaque thicknesses). Blood samples were collected for
      measurement of hs-CRP, soluble intercellular adhesion molecule (sICAM-1) and sP
      selectin at the time of baseline examination. The development of atherosclerosis
      was estimated by the formula: Deltavalue/year=(last value-baseline value)/number
      of follow-up years. Multivariate linear regression analysis revealed that sICAM-1
      was associated with DeltaIMT/year and DeltaPS/year, which was not the case for sP
      selectin. sICAM-1 was closely associated with DeltaIMT/year especially in
      patients with apparent atheromatous plaque. Our results suggested that levels of
      sICAM-1 might have predictive value of progression of carotid atherosclerosis
      independently of traditional risk factors and hs-CRP.

PMID- 15721023
TI  - The association of the apolipoprotein E gene promoter polymorphisms and
      haplotypes with serum lipid and lipoprotein concentrations.
AB  - BACKGROUND: Apolipoprotein E (ApoE) is known to modulate lipoprotein transport
      and metabolism. The common APOE epsilon2/epsilon3/epsilon4 polymorphism explains
      part of the variation in plasma cholesterol levels. Polymorphisms of the APOE
      gene regulatory region are suggested to be involved in explaining variation of
      lipoprotein levels within the APOE epsilon2/epsilon3/epsilon4 genotypes.
      OBJECTIVES: To study the associations of the APOE gene promoter polymorphisms 
      219G/T and +113G/C and their haplotypes with serum lipid and lipoprotein
      concentrations, especially within the most common APOE epsilon3/epsilon3 genotype
      group. SUBJECTS AND METHODS: From 219 middle-aged Finnish men, APOE genotypes
      were determined and haplotypes estimated. Plasma lipoproteins were isolated by
      ultracentrifugation and their lipids were measured. RESULTS: The studied APOE
      promoter polymorphisms and haplotypes associated with certain lipid variables
      independently of the APOE epsilon2/epsilon3/epsilon4 genotype. Within the APOE
      epsilon3/epsilon3 group, both -219G/G and +113G/G genotypes associated
      statistically significantly with higher levels of very low-density lipoprotein
      (VLDL) cholesterol, apoB and triglycerides, and tended to associate with lower
      HDL-cholesterol concentrations than the other genotypes. Compared with the 
      219T/+113C/epsilon3 haplotype, the more common -219G/+113G/epsilon3 haplotype was
      found more frequently among the group having high (over median) VLDL-cholesterol
      and triglyceride concentrations (OR 2.6, p<0.001 and OR=2.1, p=0.009,
      respectively). CONCLUSIONS: In addition to the APOE epsilon2/epsilon3/epsilon4
      polymorphism, the promoter polymorphisms -219G/T and +113G/C as well as their
      haplotype modulate lipid and lipoprotein concentrations in middle-aged Finnish
      men.

PMID- 15721025
TI  - Heterogeneity of cardiovascular risk among smokers is related to degree of carbon
      monoxide exposure.
AB  - BACKGROUND: Between smokers matched for daily tobacco consumption there are
      marked variations of the cardiovascular risk. This follow up of the population
      based cohort "Men born in 1914" from Malmo, Sweden, explored whether this is
      accounted for by the levels of carbon monoxide (CO). METHODS: Three hundred and
      sixty-five men without history of cardiovascular disease (CVD) were followed over
      27 years. Leg artery disease was defined as a systolic ankle-arm pressure ratio
      (ABPI) below 0.9 in either leg. Incidence of myocardial infarction (MI), stroke
      and deaths is based on linkage with regional and national registers. The
      distribution of CO in blood and expired air, respectively, was divided into
      quartiles. RESULTS: There was a significant inverse relation between ABPI and CO
      in blood and expired air. Incidence of CVD events and deaths increased
      progressively with degree of CO exposure. Men with CO in the top quartile had
      significantly increased risks of CVD events (RR: 2.2; 95% CI: 1.00-4.6) and
      cardiovascular deaths (RR: 3.2, CI: 1.2-8.3), adjusted for daily tobacco
      consumption and other potential confounders. CONCLUSIONS: In smokers, the
      prevalence of leg atherosclerosis and incidence of cardiovascular disease is
      related to the amount of carbon monoxide in blood or expired air.

PMID- 15721024
TI  - Association of apo A-IV 360 (Gln --> His) polymorphism with plasma lipids and
      lipoproteins: the Framingham Offspring Study.
AB  - The effect of a common apolipoprotein (apo) A-IV polymorphism (substitution of
      histidine for glutamine at position 360) on plasma lipid, lipoprotein cholesterol
      and lipoprotein(a) (Lp(a)) levels, and on low-density lipoprotein (LDL) particle
      size was examined by genotyping in 2322 Caucasian men and women (mean age: 48.9+/
      10.1 years) participating in the Framingham Offspring Study (FOS). The relative
      frequencies of the apo A-IV-Gln (apo A-IV-1) and the apo A-IV-His (apo A-IV-2)
      alleles were 0.932 and 0.068, respectively, and were in Hardy-Weinberg
      equilibrium. No effect of the apo A-IV-2 genotype was observed on plasma
      triglyceride, total and lipoprotein cholesterol, and LDL particle size in either
      men or women after adjustment for age and body mass index. To avoid a possible
      interaction between the apo E genotype and the apo A-IV genotype, subgroup
      analyses were undertaken in 1,414 male and female subjects with the apo E3/3
      genotype. Among women in this group there was a significant effect of the apo A
      IV-2 allele on triglyceride levels (p=0.046). This effect was no longer
      significant after adjustment for age and BMI (p=0.074). No significant allele
      effect on other lipoprotein levels, including Lp(a), was noted in apo E3/3 men or
      women. We have also conducted a meta-analysis of our own data and of other
      studies found in the literature, indicating a significant lowering effect of apo
      A-IV-2 on plasma triglycerides, but no effects on other parameters. In
      conclusion, the apo A-IV-2 allele is associated with a modest reduction in plasma
      triglyceride levels in the general population.

PMID- 15721026
TI  - Increased lipoprotein(a) is associated with reduced myocardial vasoreactivity in
      young healthy men.
AB  - OBJECTIVES AND BACKGROUND: We examined the association between lipoprotein(a) and
      myocardial vasoreactivity in healthy men. METHODS: Thirty non-smoking healthy men
      (age 34+/-6 years) were studied: 9 had increased lipoprotein(a) (>200 mg/L)
      concentrations (lipoprotein(a) 317 (range 218-550) mg/L) and 21 had normal
      lipoprotein(a) (<200 mg/L) concentrations (lipoprotein(a) 57 (range 13-156)
      mg/L). The myocardial blood flow measurements were performed basally and during
      adenosine infusion (140 microg/kg/min) with or without simultaneous physiological
      hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron
      emission tomography and [(15)O]H(2)O. RESULTS: Basal myocardial blood flow was
      similar between the subjects with increased and normal lipoprotein(a) (0.76+/
      0.20 and 0.79+/-0.20 mLg(-1) min(-1), NS). Adenosine-stimulated flow tended to be
      reduced in subjects with increased lipoprotein(a) (3.1+/-0.7 mLg(-1) min(-1)
      versus 3.7+/-1.1 mLg(-1) min(-1), respectively, p=0.1). During physiological
      hyperinsulinemia adenosine-stimulated flow was further enhanced in both groups
      but significantly blunted in subjects with increased lipoprotein(a) (3.7+/-0.8
      mLg(-1) min(-1) versus 4.8+/-1.4 mLg(-1) min(-1), respectively, p=0.03). This
      difference remained significant after simultaneous controlling for BMI, HbA1c,
      LDL-cholesterol, HDL-cholesterol and blood pressure (p=0.04). CONCLUSIONS:
      Already young healthy men with lipoprotein(a) concentrations greater than 200mg/L
      are characterized by impaired myocardial vasoreactivity.

PMID- 15721027
TI  - Hormone therapy and antioxidant vitamins do not improve endothelial vasodilator
      function in postmenopausal women with established coronary artery disease: a
      substudy of the Women's Angiographic Vitamin and Estrogen (WAVE) trial.
AB  - We measured flow-mediated dilation (FMD) by high-resolution brachial ultrasound
      in 61 women who participated in the Women's Angiographic Vitamin and Estrogen
      (WAVE) trial, a randomized controlled trial. There were no significant
      differences in the baseline demographics of women receiving hormone therapy
      (0.625 mg/day of conjugated equine estrogen plus 2.5mg of medroxyprogesterone
      acetate for women who had not had a hysterectomy) or placebo; or vitamins (400 IU
      of Vitamin E and 500 mg of Vitamin C twice daily) or placebo. Baseline FMD was
      impaired in all subjects (3.3+/-7.6%). Neither hormone therapy (4.1+/-5.2% at
      baseline, 4.2+/-5.0% at 3 months, and 4.1+/-6.5% at 34 months) nor antioxidant
      vitamins (3.0+/-8.3% at baseline; 3.5+/-4.6% at 3 months; 3.1+/-7.6% at 34
      months) improved FMD (all p-values=NS). Endothelium-independent vasodilation,
      induced by nitroglycerin (NTG) was similar at baseline and was not affected by
      either therapy. In univariate and multivariate analysis, neither hormone therapy
      nor antioxidant vitamins were associated with FMD. Women with established
      coronary artery disease have impaired flow-mediated vasodilation of the brachial
      artery that does not improve after 3 months or up to 34 months of treatment with
      postmenopausal hormone therapy or antioxidant vitamins.

PMID- 15721028
TI  - Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in
      chronic heart failure.
AB  - Although not currently indicated for chronic heart failure (CHF), statins have
      been associated with improved outcome in retrospective analysis. However, statin
      therapy reduces plasma levels of coenzyme Q(10) (ubiquinone), which may have
      adverse effects on heart failure states. We hypothesized that atorvastatin
      treatment improves endothelial function in patients with chronic heart failure
      independent of LDL-cholesterol alterations. Furthermore, we assessed how
      reductions in coenzyme Q(10) levels impact on potentially improved endothelial
      function. Twenty-four patients with stable, symptomatic heart failure (New York
      Heart Association Class II or III) and a left ventricular ejection fraction <40%
      were randomised to 40 mg atorvastatin or placebo for 6 weeks and crossed over to
      the other treatment arm for a further 6 weeks, after a 2-week wash out. Forearm
      resistance vessel function was assessed by venous occlusion plethysmography
      during infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and N(G)
      monomethyl-L-arginine (L-NMMA) into the brachial artery. Atorvastatin treatment
      lowered triglycerides, LDL-cholesterol and coenzyme Q(10) levels (all p<0.001)
      and improved endothelium-dependent vasodilatation during acetylcholine infusion
      (p=0.015). Endothelium-dependent forearm blood flow improvements correlated with
      reductions in coenzyme Q(10) levels (p=0.011), but not with LDL-cholesterol
      levels (p=0.084). Coenzyme Q(10) remained the significant variable predicting
      improvement in NO dependent endothelial function after adjusting for LDL
      cholesterol levels (p=0.041). In conclusion, short-term atorvastatin therapy
      improved endothelial function in chronic heart failure patients. Further studies
      are required to determine whether coenzyme Q(10) reductions are limiting the
      maximum favourable effects of statin therapy on the microcirculation.

PMID- 15721029
TI  - Effects of statin therapy on circulating conjugated dienes, a measure of LDL
      oxidation.

PMID- 15721030
TI  - Homocysteine is not detected in normal human vessel walls.

PMID- 15721031
TI  - Branching orders among alpha-proteobacteria and mitochondria inferred from gene
      transpositions.

PMID- 15721032
TI  - Model for the robust establishment of precise proportions in the early Drosophila
      embryo.
AB  - During embryonic development, a spatial pattern is formed in which proportions
      are established precisely. As an early pattern formation step in Drosophila
      embryos, an anterior-posterior gradient of Bicoid (Bcd) induces hunchback (hb)
      expression (Nature 337 (1989) 138; Nature 332 (1988) 281). In contrast to the Bcd
      gradient, the Hb profile includes information about the scale of the embryo.
      Furthermore, the resulting hb expression pattern shows a much lower embryo-to
      embryo variability than the Bcd gradient (Nature 415 (2002) 798). An additional
      graded posterior repressing activity could theoretically account for the observed
      scaling. However, we show that such a model cannot produce the observed precision
      in the Hb boundary, such that a fundamentally different mechanism must be at
      work. We describe and simulate a model that can account for the observed precise
      generation of the scaled Hb profile in a highly robust manner. The proposed
      mechanism includes Staufen (Stau), an RNA binding protein that appears essential
      to precision scaling (Nature 415 (2002) 798). In the model, Stau is released from
      both ends of the embryo and relocalizes hb RNA by increasing its mobility. This
      leads to an effective transport of hb away from the respective Stau sources. The
      balance between these opposing effects then gives rise to scaling and precision.
      Considering the biological importance of robust precision scaling and the
      simplicity of the model, the same principle may be employed more often during
      development.

PMID- 15721033
TI  - Amendments to the theory underlying Ussing chamber data of chloride ion secretion
      after bacterial enterotoxin exposure.
AB  - Bacterial enterotoxins may cause life-threatening diarrhoeal fluid loss in part
      because they stimulate enterocytes to secrete fluid into the small intestine as
      well as preventing normal fluid uptake. Abnormal chloride ion secretion is
      believed to provide the osmotic driving force for the inappropriate fluid
      movement. Evidence for enhanced chloride secretion consists of isotopic flux
      measurements in Ussing chambers, the standard apparatus for permeation studies.
      Flux from the lumen of the intestine is assumed to be determined solely by
      absorptive processes and flux towards the lumen solely by secretory processes.
      Bacterial enterotoxin increased flux towards the lumen is taken as an evidence of
      enhanced secretion. Examination of the flux equation solutions shows that the
      existing theoretical treatment of the Ussing chamber consists of the super
      imposition of two contradictory unidirectional models. In contrast, the present
      analysis shows that a measured 'unidirectional' flux contains information both
      about absorptive and secretory processes, regardless of which flux is measured.
      Reciprocity is predicted for the fluxes, as decreases in the absorptive processes
      will cause increases in apparent secretory flux. Data from the literature show
      that mucosal-to-serosal chloride ion flux in rabbit ileum after exposure to
      secretagogues correlates inversely and highly significantly (r=0.74, n=17,
      p<0.001) with increases in serosal-to-mucosal chloride ion flux. As a category of
      evidence, flux data do not provide conclusive evidence of enhanced chloride
      secretion after exposure to enterotoxins, since an apparently enhanced serosal-to
      mucosal flux would also be noted after inhibition of the mucosal-to-serosal flux.
      As interruption of absorptive processes can be misinterpreted as enhanced
      secretion in the Ussing chamber, this is a serious deficiency in the evidence for
      direct enterotoxin enhancement of the intestinal chloride ion channel as a basis
      for diarrhoeal disease.

PMID- 15721034
TI  - Contrasting B cell- and T cell-based protective vaccines.
AB  - A substantial research effort is devoted to the development of vaccines based on
      T cells. Such a vaccine would provide a means to protect against infection with
      HIV and stop the current pandemic. Here we investigate the possibility to develop
      a protective T cell-based vaccine. We do this by means of a mathematical model
      which describes the dynamics of a pathogen and the immune system in the early
      stages of infection. We compare an immune response that is near immediate--as is
      the case for a humoral response--with that of a response in which the effector
      cells have to be formed from precursor cells--as occurs in T cell responses. The
      latter applies to a T cell-based vaccine. A near immediate response is associated
      with a threshold number of effector cells above which an infection cannot take
      hold. For a T cell-based vaccine this threshold increases with the amount of
      antigen the immune system is exposed to. For small initial doses, as one would
      naturally expect to occur, this gives rise to impractically large thresholds.
      Thus, although a T cell vaccine might work against a high dose exposure, it might
      fail when exposed against to a low-dose exposure. This limits, we argue, the
      efficacy of T cell-based vaccines.

PMID- 15721035
TI  - A dynamic model of mouth closing movements in clariid catfishes: the role of
      enlarged jaw adductors.
AB  - Some species of Clariidae (air breathing catfishes) have extremely large
      (hypertrophied) jaw closure muscles. Besides producing higher bite forces, the
      enlarged muscles may also cause higher accelerations of the lower jaw during
      rapid mouth closure. Thus, jaw adductor hypertrophy could potentially also enable
      faster mouth closure. In this study, a forward dynamic model of jaw closing is
      developed to evaluate the importance of jaw adductor hypertrophy on the speed of
      mouth closure. The model includes inertia, pressure, tissue resistance and
      hydrodynamic drag forces on the lower jaw, which is modelled as a rotating half
      ellipse. Simulations are run for four clariid species showing a gradual increase
      in jaw adductor hypertrophy (Clarias gariepinus, Clariallabes longicauda,
      Gymnallabes typus and Channallabes apus). The model was validated using data from
      high-speed videos of prey captures in these species. In general, the kinematic
      profiles of the fastest mouth closure from each species are reasonably well
      predicted by the model. The model was also used to compare the four species
      during standardized mouth closures (same initial gape angle, travel distance and
      cranial size). These simulations suggest that the species with enlarged jaw
      adductors have an increased speed of jaw closure (in comparison with the non
      hypertrophied C. gariepinus) for short lower jaw rotations and when feeding at
      high gape angles. Consequently, the jaw system in these species seems well
      equipped to capture relatively large, evasive prey. For prey captures during
      which the lower jaw rotates freely over a larger distance before impacting the
      prey, the higher kinematic efficiency of the C. gariepinus jaw system results in
      the fastest jaw closures. In all cases, the model predicts that an increase in
      the physiological cross-sectional area of the jaw muscles does indeed contribute
      to the speed of jaw closure in clariid fish.

PMID- 15721036
TI  - Theoretical study on two-dimensional aerodynamic characteristics of unsteady
      wings.
AB  - A simple computing method based on a potential theory is developed for two
      dimensional steady and unsteady deflected wings. This method of theoretical
      analysis is essentially related to thin and angular airfoils. Thus, the method is
      very simple but is effective to forecast aerodynamic forces for deflected or
      angular airfoils with a small camber operating in high Reynolds number flow,
      specifically in unsteady motion. The suction force acting on the leading edge of
      steady airfoils is theoretically obtained by using the Blasius formula. By
      Polhamus's leading edge suction analogy, the suction force is considered to be
      directed upward in partially separated flow for real thin airfoil with sharp
      leading edge. The theory can also be applied to obtain the aerodynamic
      characteristics of thin airfoils operating on low Reynolds number flow under some
      degree of approximation. This is very useful for the unsteady aerodynamic
      analysis because the Navier-Stokes equation can be solved by neither analytical
      nor numerical method for the thin and angular airfoils, which are common in the
      insect wing.

PMID- 15721037
TI  - An efficient method for calculation of dynamic logarithmic gains in biochemical
      systems theory.
AB  - Biochemical systems theory (BST) characterizes a given biochemical system based
      on the logarithmic gains, rate-constant sensitivities and kinetic-order
      sensitivities defined at a steady state. This paper describes an efficient method
      for calculation of the time courses of logarithmic gains, i.e. dynamic
      logarithmic gains L(Xi, Xj; t), which expresses the percentage change in the
      value of a dependent variable Xi at a time t in response to an infinitesimal
      percentage change in the value of an independent variable Xj at t=0. In this
      method, one first recasts the ordinary differential equations for the dependent
      variables into an exact canonical nonlinear representation (GMA system) through
      appropriate transformations of variables. Owing to the structured mathematical
      form of this representation, the recast system can be fully described by a set of
      numeric parameters, and the differential equations for the dynamic logarithmic
      gains can be set up automatically without resource to computer algebra. A simple
      general-purpose computer program can thus be written that requires only the
      relevant numeric parameters as input to calculate the time courses of the
      variables and of the dynamic logarithmic gains for both concentrations and
      fluxes. Unlike other methods, the proposed method does not require to derive any
      expression for the partial differentiation of flux expressions with respect to
      each independent variable. The proposed method has been applied to two kinds of
      reaction models to elucidate its usefulness.

PMID- 15721038
TI  - Computational model of flow-tissue interactions in intussusceptive angiogenesis.
AB  - Angiogenesis, the growth of vascular structures, is a complex biological process
      which has long puzzled scientists. Better physiological understanding of this
      phenomenon could result in many useful medical applications such as the
      development of new methods for cancer therapy. We report on the development of a
      simple computational model of micro-vascular structure formation in
      intussusceptive angiogenesis observed in vivo. The tissue is represented by a
      discrete set of basic structural entities and flow conditions within the
      resulting domain are obtained by solving the Navier-Stokes equations. The tissue
      is then remodelled according to the tangential shear stress while approximating
      advection by means of simple non-diffusive heuristics. The updated tissue
      geometry then becomes the input for the next remodelling step. The model,
      consisting of steady-state flow and a simple mechanistic tissue response,
      successfully predicts bifurcation formation and micro-vessel separation in a
      porous cellular medium. This opens new modelling possibilities in computational
      studies of the cellular transport involved in micro-vascular growth.

PMID- 15721039
TI  - Quantitative analysis of the energy requirements for development of obesity.
AB  - OBJECTIVE: Obesity is typically developed over long time and reflected in an
      energy imbalance, which is too small to be measured and controlled. Our objective
      is to formulate a mathematical model for the relation between the change in body
      mass and the values of the energy intake and the energy expenditure, controlled
      by the physical activity factor PAF. DATA AND THEORY: The uncontrolled components
      of energy expenditure increases as result of body mass increase: expenditure of a
      larger mass and expenditure to convert matter in intake into tissue. Both
      contributions depend on the fraction of fat in the added tissue. Based on data
      from the literature, the fraction of fat in added tissue and the energy required
      to convert energy into tissue are estimated and included in the model. RESULTS:
      Application of the theory shows that an increase in body mass of 1 kg/year
      corresponds to an energy imbalance of 71 kJ/d for men. Of this imbalance, 82% are
      stored as new tissue, while 18% are used for energy conversion. If a man in
      steady state changes energy intake by 0.1 MJ/d, keeping the physical activity
      factor constant, then the corresponding increase in steady-state body mass is
      1.77 kg/PAF, and it will take 320/PAF days before half the change of body mass
      has taken place. A typical value for PAF is 1.8. CONCLUSION: Energy-based
      theoretical relations between the various factors involved in energy balance help
      identifying and quantifying the components of the energy balance and
      understanding their relations during development of obesity. The inclusion of
      increased energy expenditure to convert food energy to tissue changes previous
      estimates of the energy imbalance by about 20 percent.

PMID- 15721040
TI  - A quantitative description of the contraction of blood vessels following the
      release of noradrenaline from sympathetic varicosities.
AB  - A model is presented that highlights the principal factors determining the form
      and extent of contraction in arteries upon stimulation of their sympathetic nerve
      supply. This model incorporates a previous quantitative model of the process of
      noradrenaline (NAd) diffusion into the vascular media and reuptake into
      sympathetic varicosities during nerve stimulation (J. Theor. Biol. 226 (2004)
      359). It is also dependent on a model of how the subsequent activation of
      metabotropic receptors initiates a G-protein cascade, resulting in the production
      of inositol trisphosphate (IP3) and an increase in intracellular calcium
      concentration, [Ca2+]i, in the smooth muscle cells (J. Theor. Biol. 223 (2003)
      93). In the present work we couple this rise in [Ca2+]i to the increase in
      phosphorylated myosin bound to actin in the cells and hence determine the force
      development in arteries due to nerve stimulation. The model accounts for force
      development as a function of [Ca2+]i and for the rate of change of force as a
      function of the rate of change of [Ca2+]i in single smooth muscle cells. It also
      accounts for the characteristic time course of the force developed by the media
      of the rat-tail artery upon nerve stimulation. This consists of a rapid rise to a
      transient peak followed by a sustained plateau of contraction during the
      stimulation period, after which the contraction slowly decays back to baseline at
      a rate dependent on the strength of the stimulation. The model indicates that the
      transient peak is primarily due to the partial block of the IP3 receptor by the
      rise in [Ca2+]i and that the main determinant of the equilibrium condition
      indicated by the plateau phase is the rate of pumping of calcium into the
      sarcoplasmic reticulum. The relatively slow decline of contraction at the end of
      nerve stimulation is primarily a consequence of the slow rates of removal of NAd
      from the media by diffusion and reuptake into the sympathetic varicosities. The
      model thus provides a quantitative account of vascular smooth muscle contraction
      upon sympathetic nerve stimulation.

PMID- 15721041
TI  - Mathematical modeling of the regulation of caspase-3 activation and degradation.
AB  - Caspases are thought to be important players in the execution process of
      apoptosis. Inhibitors of apoptosis (IAPs) are able to block caspases and
      therefore apoptosis. The fact that a subgroup of the IAP family inhibits active
      caspases implies that not each caspase activation necessarily leads to apoptosis.
      In such a scenario, however, processed and enzymically active caspases should
      somehow be removed. Indeed, IAP-caspase complexes covalently bind ubiquitin,
      resulting in degradation by the 26S proteasome. Following release from
      mitochondria, IAP antagonists (e.g. second mitochondrial activator of caspases
      (Smac)) inactivate IAPs. Moreover, although pro-apoptotic factors such as
      irradiation or anti-cancer drugs may release Smac from mitochondria in tumor
      cells, high cytoplasmic survivin and ML-IAP levels might be able to neutralize it
      and, consequently, IAPs would further be able to bind activated caspases. Here,
      we propose a simple mathematical model, describing the molecular interactions
      between Smac deactivators, Smac, IAPs, and caspase-3, including the requirements
      for both induction and prevention of apoptosis, respectively. In addition, we
      predict a novel mechanism of caspase-3 degradation that might be particularly
      relevant in long-living cells.

PMID- 15721042
TI  - A feedforward loop motif in transcriptional regulation: induction and repression.
AB  - We study the dynamical behavior of a unit of three positive transcriptional
      regulators which occurs frequently in biological networks of yeast and bacteria
      as a feedforward loop. We investigate numerically a set of reactions
      incorporating the basic features of transcription and translation. We determine
      (i) how the feedforward loop motif functions as a computational element such as
      an AND gate in the presence of stochastic fluctuations, and (ii) the robustness
      of the motif when transcription at the primary level is suddenly repressed. We
      highlight the effective time-scales which underlie both of these aspects of the
      feedforward loop motif. We show how threshold behavior of the motif output arises
      as a function of the number of external inducers as well as the time over which
      the inducer acts. We discuss how individual cell behavior can deviate
      significantly from average behavior, due to intrinsic fluctuations in the small
      number of molecules present in a cell.

PMID- 15721043
TI  - Predicting enzyme family classes by hybridizing gene product composition and
      pseudo-amino acid composition.
AB  - A new method has been developed to predict the enzymatic attribute of proteins by
      hybridizing the gene product composition and pseudo amino acid composition. As a
      demonstration, a working dataset was generated with a cutoff of 60% sequence
      identity to avoid redundancy and bias in statistical prediction. The dataset thus
      constructed contains 39989 protein sequences, of which 27469 are non-enzymes and
      12520 enzymes that were further classified into 6 enzyme family classes according
      to their 6 main EC (Enzyme Commission) numbers (2314 are oxidoreductases, 3653
      transferases, 3246 hydrolases, 1307 lyases, 676 isomerases, and 1324 ligases).
      The overall success rate by the jackknife test for the identification between
      enzyme and non-enzyme was 94%, and that for the identification among the 6 enzyme
      family classes was 98%. It is anticipated that, with the rapid increase of
      protein sequences entering into databanks, the current method will become a
      useful automated tool in identifying the enzymatic attribute of a newly found
      protein sequence.

PMID- 15721044
TI  - The effect of the availability of charity care to the uninsured on the demand for
      private health insurance.
AB  - The economic reasons why some people do not obtain health insurance are unclear.
      In this paper, I test the hypothesis that the availability of charity care to the
      uninsured reduces the likelihood of obtaining private coverage. I utilize
      variation in the availability of charity care across the different markets in the
      Community Tracking Study's Household Survey (CTS-HS) using an "access to care"
      measure of the uninsured's cost-related difficulties in obtaining medical care,
      to both aggregate across the various "safety net" providers and control for its
      potentially endogenous supply. I find evidence supporting this hypothesis for low
      income people, in both the individual market and the employment-based group
      market. I also estimate a joint model of offer and take-up decisions for the
      group market sample and find that the availability of charity care reduces low
      income workers' offer rates but not their take-up rates.

PMID- 15721045
TI  - Subsidies to employee health insurance premiums and the health insurance market.
AB  - One approach to covering the uninsured that is frequently advocated by policy
      makers is subsidizing the employee portion of employer-provided health insurance
      premiums. But, since the vast majority of those offered employer-provided health
      insurance already take it up, such an approach is only appealing if there is a
      very high takeup elasticity among those who are offered and uninsured. Moreover,
      if plan choice decisions are price elastic, then such subsidies can at the same
      time increase health care costs by inducing selection of more expensive plans. We
      study an excellent example of such subsidies: the introduction of pre-tax
      premiums for postal employees in 1994, and then for the remaining federal
      employees in 2000. We do so using a census of personnel records for all federal
      employees from 1991 through 2002. We find that there is a very small elasticity
      of insurance takeup with respect to its after-tax price, and a modest elasticity
      of plan choice. Our results suggest that the federal government did little to
      improve insurance coverage, but much to increase health care expenditures,
      through this policy change.

PMID- 15721046
TI  - Cigarette tax avoidance and evasion.
AB  - Variation in state cigarette taxes provides incentives for tax avoidance through
      smuggling, legal border crossing to low tax jurisdictions, or Internet
      purchasing. When taxes rise, tax paid sales of cigarettes will decline both
      because consumption will decrease and because tax avoidance will increase. The
      key innovation of this paper is to compare cigarette sales data to cigarette
      consumption data from the Behavioral Risk Factor Surveillance System (BRFSS). I
      show that after subtracting percent changes in consumption, residual percent
      changes in sales are associated with state cigarette tax changes implying the
      existence of tax avoidance. I estimate that the tax avoidance response to tax
      changes is at least twice the consumption response and that tax avoidance
      accounted for up to 9.6% of sales between 1985 and 2001. Because of the increase
      in tax avoidance, tax paid sales data understate the level of smoking and
      overstate the drop in smoking. I also find that the level of legal border
      crossing was very low relative to other forms of tax avoidance. If states have
      strong preferences for smoking control, they must pair high cigarette taxes with
      effective policies to curb smuggling and other forms of tax avoidance or employ
      alternative policies such as counter-advertising and smoking restrictions.

PMID- 15721047
TI  - Health insurance coverage and the macroeconomy.
AB  - This paper investigates the relationship between the macroeconomy and health
      insurance coverage for non-elderly Americans. We find that, for men, state
      unemployment rate is positively correlated with the probability of health
      insurance coverage in general and through an employer in particular, and that
      these correlations are only partly explained by changes in employment status. In
      contrast, the insurance coverage of women and children appears to be insulated
      from fluctuations in the unemployment rate by public health insurance programs
      like Medicaid and State Children's Health Insurance Program (SCHIP). We estimate
      that 984,000 Americans, nearly all of whom were adult men, lost health insurance
      due to macroeconomic conditions alone during the 2001 recession.

PMID- 15721048
TI  - Productivity in pharmaceutical-biotechnology R&D: the role of experience and
      alliances.
AB  - Using data on over 900 firms for the period 1988-2000, we estimate the effect on
      phase-specific biotech and pharmaceutical R&D success rates of a firm's overall
      experience, its experience in the relevant therapeutic category, the
      diversification of its experience across categories, the industry's experience in
      the category, and alliances with large and small firms. We find that success
      probabilities vary substantially across therapeutic categories and are negatively
      correlated with mean sales by category, which is consistent with a model of
      dynamic, competitive entry. Returns to experience are statistically significant
      but economically small for the relatively straightforward phase 1 trials. We find
      evidence of large, positive and diminishing returns to a firm's overall
      experience (across all therapeutic categories) for the larger and more complex
      late-stage trials that focus on a drug's efficacy. There is some evidence that a
      drug is more likely to complete phase 3 if developed by firms whose experience is
      focused rather than broad (diseconomies of scope). There is evidence of positive
      knowledge spillovers across firms for phase 1. However, for phase 2 and phase 3
      the estimated effects of industry-wide experience are negative, which may reflect
      either higher Food and Drug Administration (FDA) approval standards in crowded
      therapeutic categories or that firms in such categories must pursue more
      difficult targets. Products developed in an alliance tend to have a higher
      probability of success, at least for the more complex phase 2 and phase 3 trials,
      and particularly if the licensee is a large firm.

PMID- 15721049
TI  - Healthy living in hard times.
AB  - Using microdata for adults from 1987 to 2000 years of the Behavioral Risk Factor
      Surveillance System (BRFSS), I show that smoking and excess weight decline during
      temporary economic downturns while leisure-time physical activity rises. The drop
      in tobacco use occurs disproportionately among heavy smokers, the fall in body
      weight among the severely obese and the increase in exercise among those who were
      completely inactive. Declining work hours may provide one reason why behaviors
      become healthier, possibly by increasing the non-market time available for
      lifestyle investments. Conversely, there is little evidence of an important role
      for income reductions. The overall conclusion is that changes in behaviors supply
      one mechanism for the procyclical variation in mortality and morbidity observed
      in recent research.

PMID- 15721050
TI  - The lasting impact of childhood health and circumstance.
AB  - We quantify the lasting effects of childhood health and economic circumstances on
      adult health, employment and socioeconomic status, using data from a birth cohort
      that has been followed from birth into middle age. Controlling for parental
      income, education and social class, children who experience poor health have
      significantly lower educational attainment, poorer health, and lower social
      status as adults. Childhood health and circumstance appear to operate both
      through their impact on initial adult health and economic status, and through a
      continuing direct effect of prenatal and childhood health in middle age. Overall,
      our findings suggest more attention be paid to health as a potential mechanism
      through which intergenerational transmission of economic status takes place:
      cohort members born into poorer families experienced poorer childhood health,
      lower investments in human capital and poorer health in early adulthood, all of
      which are associated with lower earnings in middle age-the years in which they
      themselves become parents.

PMID- 15721051
TI  - The effect of network arrangements on hospital pricing behavior.
AB  - The Department of Justice (DOJ) and the Federal Trade Commission (FTC) have taken
      a recent interest in collaborations among hospitals that do not entail common
      ownership, despite the lack of scientific evidence regarding effects of these
      hospital "networks" on market competition. This paper explores the relationship
      between hospital networks and pricing behavior in California during a period of
      dynamic increase in hospital network activity there. Using Herfindahl-Hirschman
      Indexes (HHI) market definitions based on patient origin and accounting for
      network relationships, we find a positive network effect on hospital pricing.
      However, this result appears to be generated primarily by system-owned hospitals
      that form networks to provide particular services jointly.

PMID- 15721052
TI  - A median voter model of health insurance with ex post moral hazard.
AB  - One of the main features of health insurance is moral hazard, as defined by Pauly
      [Pauly, M.V., 1968. The economics of moral hazard: comment. American Economic
      Review 58, 531-537), people face incentives for excess utilization of medical
      care since they do not pay the full marginal cost for provision. To mitigate the
      moral hazard problem, a coinsurance can be included in the insurance contract.
      But health insurance is often publicly provided. Having a uniform coinsurance
      rate determined in a political process is quite different from having different
      rates varying in accordance with one's preferences, as is possible with private
      insurance. We construct a political economy model in order to characterize the
      political equilibrium and answer questions like: "Under what conditions is there
      a conflict in society on what coinsurance rate should be set?" and "Which groups
      of individuals will vote for a higher and lower than equilibrium coinsurance
      rate, respectively?". We also extend our basic model and allow people to
      supplement the coverage provided by the government with private insurance. Then,
      we answer two questions: "Who will buy the additional coverage?" and "How do the
      coinsurance rates people are now faced with compare with the rates chosen with
      pure private provision?".

PMID- 15721053
TI  - Sex steroids and sexual desire in a man with a novel mutation of aromatase gene
      and hypogonadism.
AB  - Sexual behavior was investigated by a sexological interview in a man with
      aromatase deficiency and hypogonadism. The study was performed at the end of a
      long testosterone treatment, during transdermal estradiol treatment and during
      estradiol and testosterone associated treatment. Sexual behavior did not show
      abnormalities. As assessed by a sexological interview and by a sexological
      questionnaire gender-identity was male, sexual orientation was heterosexual and
      libido was normal. Sexual function was limited to masturbation and was seemingly
      unaffected by testosterone or estradiol alone; only the associated treatment
      induced a great increase in libido and in frequency of masturbation and sexual
      fantasies when both testosterone and estradiol reached the range of normality.
      Sexual behavior is mainly under the control of cognitive functions in men, but
      sex steroids may modulate some aspects of male sexuality. Our findings suggest
      that in men estrogens could play a role in sexual activity.

PMID- 15721054
TI  - Testosterone's anti-anxiety and analgesic effects may be due in part to actions
      of its 5alpha-reduced metabolites in the hippocampus.
AB  - Although testosterone (T) may have effects to enhance analgesia and reduce
      anxiety, its effects and mechanisms are not well understood. We hypothesized that
      if T's anti-anxiety and analgesic effects are due in part to actions of its
      5alpha-reduced metabolite (dihydrotestosterone-DHT) and/or its 3alpha
      hydroxysteroid dehydrogenase reduced metabolite (3alpha-androstanediol-3alpha
      diol), in the hippocampus, then androgen regimens that increase levels of these
      metabolites in the hippocampus should produce anti-anxiety behavior, and
      analgesic effects, in gonadectomized (GDX) male rats. In Experiment 1, GDX rats
      were administered T, DHT, 3alpha-diol (1 mg/kg, SC), or vehicle. In Experiment 2,
      GDX rats had T, DHT, 3alpha-diol-containing inserts, or empty control inserts
      applied to the dorsal hippocampus immediately prior to behavioral testing.
      Androgen-administered rats (SC or intrahippocampal) showed significantly more
      exploratory behavior in the open field and elevated plus maze, less freezing in
      response to shock, and longer tailflick and pawlick latencies. These findings
      suggest that T's anti-anxiety effects may be due in part to actions of its 5alpha
      reduced metabolites in the dorsal hippocampus.

PMID- 15721055
TI  - Male patients with paranoid schizophrenia have greater ACTH and cortisol
      secretion in response to metoclopramide-induced AVP release.
AB  - Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has
      yielded conflicting results, which may be related to patient selection and
      previous exposure to psychotropic medication. The objective of this study was to
      determine the pattern of corticotropin (ACTH) and cortisol release in response to
      metoclopramide (a dopamine antagonist), which appears to be unique in its ability
      to release vasopressin (AVP), in drug naive patients with schizophrenia
      experiencing their first episode of psychosis. In this study, we examined AVP,
      ACTH and cortisol release in response to metoclopramide in 10 drug-naive, first
      episode male patients with a DSM IV diagnosis of paranoid schizophrenia and
      compared them to healthy control subjects matched for age, sex and smoking
      status. Patients, as compared to controls had higher levels of baseline plasma
      cortisol (375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l, respectively; t=2.48, df=9, p<
      0.02) and plasma ACTH (14.9+/-0.85 vs. 11.3+/-0.57 pg/ml, respectively; t=4.29,
      df=9, p<0.001). AVP levels were lower in patients though this did not reach
      statistical significance (0.89+/-0.09 vs. 1.3+/-0.08 pmol/l, respectively;
      t=1.97, df=9, p<0.07). A repeated measures 2-way ANOVA to compare responses to
      metoclopramide over time between the two groups yielded a significant group by
      time interaction for cortisol (F=11.3, df=6, 108, p<0.001) and ACTH (F=15.65,
      df=6, 108, p<0.002). Post hoc Tukey's test revealed significant differences
      between the two groups at +30, +45, +60, +90 and +120 min for cortisol (p<0.01)
      and at +30, +45, +60 and +90 min for ACTH (p<0.01). The group by time
      interactions continued to remain significant when cortisol (F=10.9, df=6, 107,
      p<0.001) and ACTH (F=13.04, df=6, 108, p<0.002) were entered as co-variates.
      There was a significant positive correlation between AVP and cortisol responses
      in patients (r=0.65, df=8, p<0.01). Male patients with paranoid schizophrenia
      release greater amounts of ACTH and cortisol in responses to metoclopramide
      induced AVP secretion than control subjects.

PMID- 15721056
TI  - Affective responses to changes in day length in Siberian hamsters (Phodopus
      sungorus).
AB  - The goal of these experiments was to test the hypothesis that day length
      influences anxious- and depressive-like behaviors in reproductively photoperiodic
      rodents. Male and female Siberian hamsters (Phodopus sungorus) were exposed to
      long (16 h light/day; LD) or short (8 h light/day; SD) photoperiods beginning at
      the time of weaning (day 18). Two weeks later hamsters were subjected to a series
      of behavioral tests to quantify anxiety-and depressive-like behaviors. In an
      elevated plus maze, SD males exhibited longer latencies to enter an open arm,
      entered fewer open arms, and spent less time exploring open arms relative to LD
      hamsters. SD males were likewise slower to enter either of the distal arms of a
      completely enclosed T-maze, and in a hunger-motivated exploratory paradigm SD
      males were slower to enter an open arena for food as compared to LD males. In a
      forced-swimming model of behavioral despair, SD males exhibited immobility
      sooner, more often, and for a greater total amount of time relative to LD males.
      Total activity levels, aversiveness to light, olfactory function, and limb
      strength were unaffected by SD, suggesting that the behavioral changes consequent
      to SD are not attributable to sensory or motor deficits, but rather may arise
      from changes in general affective state. The anxiogenic and depressive effects of
      SD were largely absent in female hamsters. Together the results indicate that
      adaptation to short photoperiods is associated with increased expression of
      anxiety- and depressive-like behaviors relative to those observed under LD
      photoperiod conditions.

PMID- 15721057
TI  - Increase in epinephrine excretion is associated with cognitive decline in elderly
      men: MacArthur studies of successful aging.
AB  - BACKGROUND: High stress hormone levels are associated with increased risk of
      cognitive decline in elderly individuals. However, the effect of late-life
      changes in stress hormone levels on cognitive decline risk has not been examined.
      Our objective was to investigate whether increase over time in urinary
      epinephrine excretion in older adults was associated with subsequent cognitive
      decline. METHODS: Measurements were made on 154 high-functioning men and women,
      70-79 years of age, in 1988, 1991, and 1995. Twelve-hour overnight urinary
      excretion of epinephrine (normalized by creatinine excretion to adjust for body
      size) was recorded in 1988 and 1991. Cognitive functioning was assessed in 1991
      and 1995 by summary scores based on standard tests of language, memory,
      abstraction, spatial recognition, and spatial construction. RESULTS: Compared to
      individuals whose epinephrine excretion decreased between 1988 and 1991, the
      individuals whose epinephrine excretion increased over the same period had
      greater subsequent declines in summary cognitive scores between 1991 and 1995.
      After adjusting for baseline epinephrine, baseline cognitive function, and
      relevant covariates, and stratifying by gender, increases in urine epinephrine
      were positively associated with cognitive decline only in men. CONCLUSIONS: We
      conclude that increase in urinary excretion of epinephrine predicts subsequent
      cognitive decline in older men.

PMID- 15721058
TI  - Brain processing of visual sexual stimuli in treated and untreated hypogonadal
      patients.
AB  - OBJECTIVE: Although various brain regions have been shown to respond to the
      presentation of visual sexual stimuli (VSS), whether these regions are
      specifically mediating sexual arousal or whether they mediate general emotional
      or motivational arousal is unknown. To clarify this issue, our purpose was to map
      the regions where the response to VSS was related to plasma testosterone.
      Specific objectives were (i) to identify regions that respond differentially to
      VSS in untreated hypogonadal patients compared with healthy controls and (ii) to
      identify in hypogonadal patients the regions that respond differentially to VSS
      as a function of therapeutically induced increased testosterone levels. METHOD:
      In nine male hypogonadal patients, in the same patients under treatment, and in
      eight healthy males, we used Positron Emission Tomography to investigate
      responses of regional cerebral blood flow to VSS. Statistical Parametric Mapping
      was used to locate regions that demonstrated a differential response. RESULTS:
      Regions responding differentially both in untreated patients compared with
      controls and in untreated patients compared with themselves under treatment were
      the right orbitofrontal cortex, insula and claustrum, where the activation was
      higher in controls than in untreated patients and where activation increased
      under treatment, and the left inferior frontal gyrus, that demonstrated a
      deactivation only in controls and in patients under treatment. That these
      responses appear to depend on testosterone indicates that these regions mediate
      sexual arousal and not only a process of general emotional or motivational
      arousal.

PMID- 15721059
TI  - Determinants of salivary cortisol levels in 10-12 year old children; a population
      based study of individual differences.
AB  - The hypothalamic-pituitary-adrenal (HPA)-axis is a central component of the
      body's neuroendocrine response to stress. Its major end-product cortisol has
      profound effects on mood and behavior. Although it has often been suggested, it
      remains unknown whether differences in HPA-axis physiology are part of an
      individual's vulnerability to psychopathology, and constitute a causal factor in
      its development. In order to study the contribution of HPA-axis physiology to the
      development of psychopathology, we measured HPA-axis physiology in a community
      cohort of 1768 10-12 year-old children. The aims of the here presented study were
      twofold: (1) to obtain data on HPA-axis function in a large cohort of pre- and
      early-adolescent children, both in terms of total hormonal output and in terms of
      the dynamics of cortisol secretion (by means of the cortisol awakening response);
      and (2) to study potential confounders of the cortisol-psychopathology
      relationship in this age group, such as season of sampling, age, gender, pubertal
      development, perinatal variables and BMI. We found a wide interindividual
      variability in HPA-axis function. An increase in cortisol in the first 30 min
      after awakening was present in 70.7% of children, but the increase appears lower
      in children than in adults. In addition, this study suggests that season of
      sampling and gender may act as potential confounders in the cortisol
      psychopathology relationship. We will follow these children longitudinally for
      the development of psychopathology in the period from childhood into adulthood.
      This period covers adolescence, which is a critical time for the appearance and
      development of psychiatric disorders.

PMID- 15721060
TI  - Processing of food stimuli is selectively enhanced during insulin-induced
      hypoglycemia in healthy men.
AB  - Recently it has been reported that during insulin-induced hypoglycemia selective
      attention is directed to food stimuli suggesting an adaptive cognitive strategy
      to escape from this potentially dangerous metabolic state. Here, we tested this
      hypothesis using a short-term memory task. We also aimed to define a hypoglycemic
      threshold level at which such an adaptive cognitive strategy first occurs.
      Fifteen healthy men underwent stepwise hypoglycemic (plasma glucose: 4.1-3.6-3.1
      2.6 mmol/l) and euglycemic clamp experiments. Clamps were performed in a single
      blind fashion within a cross-over design with the order balanced across subjects.
      During the clamps cognitive function tests (short-term recall of food-related and
      non-food-related words; Stroop task) were applied at baseline and each
      hypoglycemic plateau, and at the corresponding time intervals of the euglycemic
      clamp. Performance on all cognitive function tests applied deteriorated during
      the hypoglycemic as compared to the euglcemic clamp (all P<0.02). Separate
      analyses at each hypoglycemic plateau revealed that food and non-food related
      short-term memory was similar during baseline and mild hypoglycemia. However, at
      the hypoglycemic target level of 2.6 mmol/l recall of food related words was
      higher than non-food related words when compared to the euglycemic control clamp
      condition (p=0.024). Performance on the word-color conflict Stroop task became
      significantly impaired first at the lowest hypoglycemic plateau (2.6 mmol/l),
      while performance on the Stroop subtests 'color naming' and 'word reading' were
      already impaired at higher plasma glucose levels (3.6 and 3.1 mmol/l;
      respectively). Collectively, data of the Stroop task indicate that the control of
      attention via executive mechanisms is less sensitive to insulin-induced
      hypoglycemia than pre-attentive automated stimulus processing (reading, naming).
      If executive control of attention becomes affected by hypoglycemia, cognitive
      resources appear to be preferentially allocated to the processing of food
      stimuli.

PMID- 15721061
TI  - Plasma cortisol levels, brain volumes and cognition in healthy elderly men.
AB  - PURPOSE: In ageing animals, exposure to chronic high levels of glucocorticoids is
      associated with cognitive impairment and hippocampal atrophy. However, there are
      few studies examining relationships among glucocorticoids, brain volumes and
      cognitive function in healthy older humans. This study examined the hypotheses
      that higher plasma cortisol levels and altered sensitivity to glucocorticoids are
      associated with worse cognition and more brain atrophy in elderly men. MATERIALS
      AND METHODS: Ninety-seven healthy men aged 65-70 had plasma cortisol measured at
      09:00, 14:30 h, and post-dexamethasone (0.25mg, 09:00 h), and had dermal
      sensitivity to glucocorticoids measured. They also underwent cognitive testing,
      with scores adjusted for estimated prior mental ability, and had MRI measurements
      of intracranial area (a validated estimate of intracranial capacity), and
      hippocampus, temporal lobe and frontal lobe volumes. RESULTS: Plasma cortisol
      levels at 09:00 h were significantly and negatively correlated with a summary
      General Cognitive Factor accounting for 51% of the variance of cognitive function
      (rho=-0.22, p=0.035), and specific cognitive tests: delayed paragraph recall
      (rho=-0.28, p=0.036) and processing speed (rho=-0.23, p=0.026). Regional brain
      volumes adjusted for intracranial area generally did not correlate with cortisol
      levels. Tissue glucocorticoid sensitivity did not correlate with any measure of
      cognition or brain volume. CONCLUSIONS: In healthy older men, higher plasma
      cortisol levels are associated with worse ageing-related overall cognitive change
      but not ageing-related brain atrophy.

PMID- 15721062
TI  - In search of seizure prediction: a critique.

PMID- 15721063
TI  - The First International Collaborative Workshop on Seizure Prediction: summary and
      data description.
AB  - The First International Collaborative Workshop on Seizure Prediction was held at
      the Department of Epileptology, University of Bonn, in Bonn, Germany on April 24
      28, 2002. Organized by the Universities of Pennsylvania and Bonn, and funded by
      grants from the American Epilepsy Society, the German Section of the
      International League against Epilepsy, and the German Section of the
      International Federation of Clinical Neurophysiology, the workshop was attended
      by 51 researchers from 16 centers in seven countries. There were four major goals
      for the workshop: (1) to host a one-day didactic session on the science of
      seizure prediction, with lectures by leaders in the field; (2) to assess the
      current state of the field by applying current methods used to predict seizures
      to a shared set of continuous intracranial EEG data and discussing the strengths
      and weaknesses of each approach; (3) to establish a consensus on minimal data
      requirements, a common nomenclature, and objective methods for comparing system
      performance across platforms and laboratories for seizure prediction research;
      and most importantly (4) to establish a multi-laboratory, international working
      group dedicated to understanding seizure generation and making on-line,
      prospective seizure prediction a reality. Following the didactic course, each
      participating group presented their results, after applying their seizure
      prediction methods to five common data sets agreed upon in advance and
      distributed before the meeting. What follows is a description of the shared data
      set used for analysis, a summary of the major discussion points from the
      workshop, and points of consensus among the group. The brief discussion serves as
      a common introduction to the research papers that follow in this issue, and the
      description of the shared data is referenced in each of these papers.
      Participants in the workshop are listed at the end of the Conclusions section, in
      alphabetical order.

PMID- 15721064
TI  - A multi-feature and multi-channel univariate selection process for seizure
      prediction.
AB  - OBJECTIVE: To develop a prospective method for optimizing seizure prediction,
      given an array of implanted electrodes and a set of candidate quantitative
      features computed at each contact location. METHODS: The method employs a genetic
      based selection process, and then tunes a probabilistic neural network classifier
      to predict seizures within a 10 min prediction horizon. Initial seizure and
      interictal data were used for training, and the remaining IEEG data were used for
      testing. The method continues to train and learn over time. RESULTS: Validation
      of these results over two workshop patients demonstrated a sensitivity of 100%,
      and 1.1 false positives per hour for Patient E, using a 2.4s block predictor, and
      a failure of the method on Patient B. CONCLUSIONS: This study demonstrates a
      prospective, exploratory implementation of a seizure prediction method designed
      to adapt to individual patients with a wide variety of pre-ictal patterns,
      implanted electrodes and seizure types. Its current performance is limited likely
      by the small number of input channels and quantitative features employed in this
      study, and segmentation of the data set into training and testing sets rather
      than using all continuous data available. SIGNIFICANCE: This technique
      theoretically has the potential to address the challenge presented by the
      heterogeneity of EEG patterns seen in medication-resistant epilepsy. A more
      comprehensive implementation utilizing all electrode sites, a broader feature
      library, and automated multi-feature fusion will be required to fully judge the
      method's potential for predicting seizures.

PMID- 15721066
TI  - Accumulated energy revisited.
AB  - OBJECTIVE: To examine the seizure prediction and detection abilities of the
      accumulated energy on multi-center data submitted to the First International
      Collaborative Workshop on Seizure Prediction. METHODS: The accumulated energy
      (AE), windowed average power, and FHS seizure detection algorithm were applied to
      a single channel of ECoG data taken from the data sets contributed to the
      workshop. The FHS seizure detection algorithm was used to perform automated
      scoring of the data in order to locate subclinical events not picked up by the
      centers where the data was collected. The results were analyzed retrospectively,
      comparing the behavior of the accumulated energy and windowed average power on
      segments containing seizures to interictal segments. RESULTS: Accumulated energy
      curves showed no divergence from interictal curves prior to seizure. Distinctive
      or clear increases in the AE slope occurred sometime at or after electrographic
      seizure onset for some seizures. Similarly, the windowed average power showed no
      consistent increases in broadband energy prior to seizures. However, both methods
      may have detection ability for some seizures. CONCLUSIONS: The accumulated energy
      did not appear to have predictive abilities for these data sets. Some detection
      ability was apparent. SIGNIFICANCE: In data unsorted by sleep/wake state, no
      seizure prediction was evident. The lack of prediction calls into question the
      existence of a preictal state as previously claimed in the literature using this
      method.

PMID- 15721065
TI  - Continuous energy variation during the seizure cycle: towards an on-line
      accumulated energy.
AB  - OBJECTIVE: Increases in accumulated energy on intracranial EEG are associated
      with oncoming seizures in retrospective studies, supporting the idea that
      seizures are generated over time. Published seizure prediction methods require
      comparison to 'baseline' data, sleep staging, and selecting seizures that are not
      clustered closely in time. In this study, we attempt to remove these constraints
      by using a continuously adapting energy threshold, and to identify stereotyped
      energy variations through the seizure cycle (inter-, pre-, post- and ictal
      periods). METHODS: Accumulated energy was approximated by using moving averages
      of signal energy, computed for window lengths of 1 and 20 min, and an adaptive
      decision threshold. Predictions occurred when energy within the shorter running
      window exceeded the decision threshold. RESULTS: Predictions for time horizons of
      less than 3h did not achieve statistical significance in the data sets analyzed
      that had an average inter-seizure interval ranging from 2.9 to 8.6h. 51.6% of
      seizures across all patients exhibited stereotyped pre-ictal energy bursting and
      quiet periods. CONCLUSIONS: Accumulating energy alone is not sufficient for
      predicting seizures using a 20 min running baseline for comparison. Stereotyped
      energy patterns through the seizure cycle may provide clues to mechanisms
      underlying seizure generation. SIGNIFICANCE: Energy-based seizure prediction will
      require fusion of multiple complimentary features and perhaps longer running
      averages to compensate for post-ictal and sleep-induced energy changes.

PMID- 15721067
TI  - Long-term prospective on-line real-time seizure prediction.
AB  - OBJECTIVE: Epilepsy, one of the most common neurological disorders, constitutes a
      unique opportunity to study the dynamics of spatiotemporal state transitions in
      real, complex, nonlinear dynamical systems. In this study, we evaluate the
      performance of a prospective on-line real-time seizure prediction algorithm in
      two patients from a common database. METHODS: We previously demonstrated that
      measures of chaos and angular frequency, estimated from electroencephalographic
      (EEG) signals recorded at critical sites in the cerebral cortex, progressively
      converge (i.e. become dynamically entrained) as the epileptic brain transits from
      the asymptomatic interictal state to the ictal state (seizure) (Iasemidis et al.,
      2001, 2002a, 2003a). This observation suggested the possibility of developing
      algorithms to predict seizures well ahead of their occurrences. One of the
      central points in those investigations was the application of optimization
      theory, specifically quadratic zero-one programming, for the selection of the
      critical cortical sites. This current study combines that observation with a
      dynamical entrainment detection method to prospectively predict epileptic
      seizures. The algorithm was tested in two patients with long-term (107.54h) and
      multi-seizure EEG data B and C (Lehnertz and Litt, 2004). RESULTS: Analysis from
      the 2 test patients resulted in the prediction of up to 91.3% of the impending 23
      seizures, about 89+/-15min prior to seizure onset, with an average false warning
      rate of one every 8.27h and an allowable prediction horizon of 3h. CONCLUSIONS:
      The algorithm provides warning of impending seizures prospectively and in real
      time, that is, it constitutes an on-line and real-time seizure prediction scheme.
      SIGNIFICANCE: These results suggest that the proposed seizure prediction
      algorithm could be used in novel diagnostic and therapeutic applications in
      epileptic patients.

PMID- 15721068
TI  - Multivariate linear discrimination of seizures.
AB  - OBJECTIVE: To discriminate seizures from interictal dynamics based on
      multivariate synchrony measures, and to identify dynamics of a pre-seizure state.
      METHODS: A linear discriminator was constructed from two different measures of
      synchronization: cross-correlation and phase synchronization. We applied this
      discriminator to a sequence of seizures recorded from the intracranial EEG of a
      patient monitored over 6 days. RESULTS: Surprisingly, we found that this
      bivariate measure of synchronization was not a reliable seizure discriminator for
      7 of 9 seizures. Furthermore, the method did not appear to reliably detect a pre
      seizure state. An association between anti-convulsant dosage, frequency of
      clinical seizures, and discriminator performance was noted. CONCLUSIONS: Using a
      bivariate measure of synchronization failed to reliably differentiate seizures
      from non-seizure periods in these data, nor did such methods show reliable
      detection of a synchronous pre-seizure state. The non-stationary variables of
      decreasing antiepileptic medication (without available serum concentration
      measurements), and concomitant increasing seizure frequency contributed to the
      difficulties in validating a seizure prediction tool on such data. SIGNIFICANCE:
      The finding that these seizures were not a simple reflection of increasing
      synchronization in the EEG has important implications. The non-stationary
      characteristics of human post-implantation intracranial EEG is an inherent
      limitation of pre-resection data sets.

PMID- 15721069
TI  - Signal complexity and synchrony of epileptic seizures: is there an identifiable
      preictal period?
AB  - OBJECTIVE: Epileptic seizures are characterized by increases in synchronized
      activity and increased signal complexity. Prediction of seizures depends upon
      detectable preictal changes before the actual ictal event. The studies reported
      here test whether two methods designed to detect changes in synchrony and
      complexity can identify any changes in a preictal period before visual EEG
      changes or clinical manifestations. METHODS: Two methods are used to characterize
      different, but linked, properties of the signal-complexity and synchrony. The
      Gabor atom density (GAD) method allows for quantification of the time-frequency
      components of the EEG and characterizes the complexity of the EEG signal. The
      measure S, based on the goodness of fit of a multivariable autoregressive model,
      allows for characterization of the degree of synchrony of the EEG signal.
      RESULTS: Complex partial seizures produce very specific patterns of increased
      signal complexity and subsequent postictal low complexity states. The measure S
      shows increased synchronization later including a prolonged period of increased
      synchrony in the postictal period. No significant preictal changes were seen
      unless contaminated by residual postictal changes in closely clustered seizures.
      CONCLUSIONS: Both GAD and S measures reveal ictal and prolonged postictal
      changes; however, there were no significant preictal changes in either complexity
      or synchrony. Any application of methods to detect preictal changes must be
      tested on seizures sufficiently separated to avoid residual postictal changes in
      the potential preictal period.

PMID- 15721070
TI  - Preictal state identification by synchronization changes in long-term
      intracranial EEG recordings.
AB  - OBJECTIVE: There is accumulated evidence that mesial temporal lobe seizures are
      preceded by a preictal transition that evolves over minutes to hours. In the
      present study, we investigated these possible preictal changes in long-term
      intracranial recordings of five patients by a measure of phase synchronization.
      In order to clearly distinguish preictal changes from all the other interictal
      states, we developed an automatic extraction of representative patterns of
      interictal synchronization activity. This reference library was used to classify
      the successive synchronization patterns of long-term recordings into groups of
      similar patterns. Altered states of brain synchronization were identified as
      deviating from patterns in the reference library and were evaluated relative to
      the times of seizure onset in terms of sensitivity and specificity. METHODS: A
      phase-locking measure was estimated using a sliding window analysis on 15
      frequency bands (2Hz steps between 0 and 30Hz), for all pairs of EEG channels in
      the epileptogenic temporal lobe (14-20 channels), over the entire data sets
      (total analyzed duration 305h). The preictal identification encompasses three
      basic stages: (1) a preprocessing stage involving the determination of a
      reference library of characteristic interictal synchronization patterns using a K
      means algorithm, and the identification of discriminant variables differentiating
      interictal from preictal states, (2) a classification stage of the
      synchronization pattern via a minimum Mahalanobis distance to the reference
      patterns, as well as detection of outliers, (3) an evaluation stage of the
      sensitivity and specificity of the detection by receiver-operating characteristic
      curves. RESULTS: In most of the cases (36 of 52 seizures, i.e. 70%), a specific
      state of brain synchronization can be observed several hours before the actual
      seizure. The changes involved both increases and decreases of the synchronization
      levels, occurring mostly within the 4-15Hz frequency band, and were often
      localized near the primary epileptogenic zone. CONCLUSIONS: The analysis of phase
      synchronization offers a way to distinguish between a preictal state and normal
      interictal activity. These findings suggest that brain synchronizations are
      preictally altered in the epileptogenic temporal lobe, inducing a pathological
      state of higher susceptibility for seizure activity. SIGNIFICANCE: Phase
      synchronization is capable of extracting information from the EEG that allow the
      definition of a preictal state. Although the proposed analysis does not
      constitute genuine seizure anticipation, these changes in neuronal
      synchronization may provide helpful information for prospective seizure warning.

PMID- 15721071
TI  - On the predictability of epileptic seizures.
AB  - OBJECTIVE: An important issue in epileptology is the question whether information
      extracted from the EEG of epilepsy patients can be used for the prediction of
      seizures. Several studies have claimed evidence for the existence of a pre
      seizure state that can be detected using different characterizing measures. In
      this paper, we evaluate the predictability of seizures by comparing the
      predictive performance of a variety of univariate and bivariate measures
      comprising both linear and non-linear approaches. METHODS: We compared 30
      measures in terms of their ability to distinguish between the interictal period
      and the pre-seizure period. After completely analyzing continuous inctracranial
      multi-channel recordings from five patients lasting over days, we used ROC curves
      to distinguish between the amplitude distributions of interictal and preictal
      time profiles calculated for the respective measures. We compared different
      evaluation schemes including channelwise and seizurewise analysis plus constant
      and adaptive reference levels. Particular emphasis was placed on statistical
      validity and significance. RESULTS: Univariate measures showed statistically
      significant performance only in a channelwise, seizurewise analysis using an
      adaptive baseline. Preictal changes for these measures occurred 5-30 min before
      seizures. Bivariate measures exhibited high performance values reaching
      statistical significance for a channelwise analysis using a constant baseline.
      Preictal changes were found at least 240 min before seizures. Linear measures
      were found to perform similar or better than non-linear measures. CONCLUSIONS:
      Results provide statistically significant evidence for the existence of a
      preictal state. Based on our findings, the most promising approach for
      prospective seizure anticipation could be a combination of bivariate and
      univariate measures. SIGNIFICANCE: Many measures reported capable of seizure
      prediction in earlier studies are found to be insignificant in performance, which
      underlines the need for statistical validation in this field.

PMID- 15721072
TI  - Intraoperative facial motor evoked potential monitoring with transcranial
      electrical stimulation during skull base surgery.
AB  - OBJECTIVE: To address the limitations of standard electromyography (EMG) facial
      nerve monitoring techniques by exploring the novel application of multi-pulse
      transcranial electrical stimulation (mpTES) to myogenic facial motor evoked
      potential (MEP) monitoring. METHODS: In 76 patients undergoing skull base
      surgery, mpTES was delivered through electrodes 1cm anterior to C1 and C2 (M1
      M2), C3 and C4 (M3-M4) or C3 or C4 and Cz (M3/M4-Mz), with the anode
      contralateral to the operative side. Facial MEPs were monitored from the
      orbicularis oris muscle on the operative side. Distal facial nerve excitation was
      excluded by the absence of single pulse responses and by onset latency consistent
      with a central origin. RESULTS: M3/M4-Mz mpTES (n=50) reliably produced facial
      MEPs while M1-M2 (n=18) or M3-M4 (n=8) stimulation produced 6 technical failures.
      Facial MEPs could be successfully monitored in 21 of 22 patients whose proximal
      facial nerves were inaccessible to direct stimulation. Using 50, 35 and 0% of
      baseline amplitude criteria, significant facial deficits were predicted with a
      sensitivity/specificity of 1.00/0.88, 0.91/0.97 and 0.64/1.00, respectively.
      CONCLUSIONS: Facial MEPs can provide an ongoing surgeon-independent assessment of
      facial nerve function and predict facial nerve outcome with sufficiently useful
      accuracy. SIGNIFICANCE: This method substantially improves facial nerve
      monitoring during skull base surgery.

PMID- 15721073
TI  - Orderly activation of human motor neurons using electrical ramp prepulses.
AB  - OBJECTIVE: Conventional electrical stimulation (rectangular pulses) recruits
      large before small diameter motor neurons and motor neurons close to the
      electrode before more distant motor neurons. The present study investigated the
      possibility for changing the recruitment order of electrical stimuli with sub
      threshold ramp prepulses. METHODS: The median nerve was stimulated using surface
      electrodes at the wrist and elbow. Compound motor action potentials were recorded
      from abductor pollicis brevis and flexor carpi radialis. Stimulus-response
      curves, nerve conduction velocity and excitation thresholds of abductor pollicis
      brevis and flexor carpi radials, with and without ramp prepulses, were recorded
      in order to study the effect of ramp prepulses on axonal excitability. RESULTS:
      The conduction velocity of the initial response (10% of the maximal response) was
      decreased by 4.3+/-0.83m/s with ramp prepulses (500ms, 80% of the excitation
      threshold). The ramp prepulses also had a differential effect on the excitation
      thresholds of abductor pollicis brevis and flexor carpi radialis. In addition,
      ramp prepulses increased the threshold of 10% of the maximal response more than
      the threshold of 90% of the maximal response. CONCLUSIONS: These results
      demonstrate that large diameter and motor neurons close to the electrode
      accommodate more to ramp prepulses than small diameter and distant motor neurons,
      which suggests that ramp prepulses may be used to change the recruitment order of
      rectangular pulses. SIGNIFICANCE: This technique of ramp prepulses allows
      stimulation of alternate subsets of motor nerves.

PMID- 15721074
TI  - Comparison between short train, monophasic and biphasic repetitive transcranial
      magnetic stimulation (rTMS) of the human motor cortex.
AB  - OBJECTIVE: To compare motor evoked potentials (MEPs) elicited by short train,
      monophasic, repetitive transcranial magnetic stimulations (rTMS) with those by
      short train, biphasic rTMS. METHODS: Subjects were 13 healthy volunteers. Surface
      electromyographic (EMG) responses were recorded from the right first dorsal
      interosseous muscle (FDI) in several different stimulation conditions. We gave
      both monophasic and biphasic rTMS over the motor cortex at a frequency of 0.5, 1,
      2 or 3Hz. To study excitability changes of the spinal cord, we also performed 3Hz
      rTMS at the foramen magnum level [Ugawa Y, Uesaka Y, Terao Y, Hanajima R,
      Kanazawa I. Magnetic stimulation of corticospinal pathways at the foramen magnum
      level in humans. Ann Neurol 1994;36:618-24]. We measured the size and latency of
      each of 20 MEPs recorded in the different stimulation conditions. RESULTS: 2 or
      3Hz stimulation with either monophasic or biphasic pulses evoked MEPs that
      gradually increased in amplitude with the later MEPs being significantly larger
      than the earlier ones. Monophasic rTMS showed much more facilitation than
      biphasic stimulation, particularly at 3Hz. Stimulation at the foramen magnum
      level at 3Hz elicited fairly constant MEPs. CONCLUSIONS: The enhancement of
      cortical MEPs with no changes of responses to foramen magnum level stimulation
      suggests that the facilitation occurred at the motor cortex. We hypothesize that
      monophasic TMS has a stronger short-term effect during repetitive stimulation
      than biphasic TMS because monophasic pulses preferentially activate one
      population of neurons oriented in the same direction so that their effects
      readily summate. Biphasic pulses in contrast may activate several different
      populations of neurons (both facilitatory and inhibitory) so that summation of
      the effects is not so clear as with monophasic pulses. When single stimuli are
      applied, however, biphasic TMS is thought to be more powerful than monophasic TMS
      because the peak-to-peak amplitude of stimulus pulse is higher and its duration
      is longer when the same intensity of stimulation (the same amount of current is
      stored by the stimulator) is used. SIGNIFICANCE: This means that when using rTMS
      as a therapeutic tool or in research fields, the difference in waveforms of
      magnetic pulses (monophasic or biphasic) may affect the results.

PMID- 15721076
TI  - Progression of P300 in a patient with bilateral hippocampal lesions.
AB  - OBJECTIVE: To evaluate the effects of hippocampal damages on P300 of event
      related potentials (ERPs). METHODS: ERPs were recorded over about 8 months using
      the auditory oddball paradigm in a patient with bilateral hippocampal lesions
      confirmed on brain magnetic resonance imaging. Findings were compared with those
      from clinical electroencephalography (periodic lateralized epileptiform
      discharges (PLEDs) or bilateral independent PLEDs (BIPLEDs)). The patient
      displayed no marked clinical symptoms aside from mild memory impairment during
      this time, and was able to fully perform the oddball task. RESULTS: Clearly
      identifiable P300 were present in all recordings. Furthermore, increases in the
      number of right PLEDs were significantly correlated with increases in P300
      latency. CONCLUSIONS: Two key results were apparent. First, the appearance of
      P300 in all ERP recordings supports the suggestion that the hippocampus is not
      indispensable for P300 generation. Second, the correlation between the number of
      PLEDs and P300 latency supports the suggestion that the hippocampus affect the
      components of P300 latency. SIGNIFICANCE: This case thus offers very suggestive
      evidence regarding the generation of P300.

PMID- 15721075
TI  - Steady state visual evoked potential abnormalities in schizophrenia.
AB  - OBJECTIVE: The steady state visual evoked potential (SSVEP) can be used to test
      the frequency response function of neural circuits. Previous studies have shown
      reduced SSVEPs to alpha and lower frequencies of stimulation in schizophrenia. We
      investigated SSVEPs in schizophrenia at frequencies spanning the theta (4Hz) to
      gamma (40Hz) range. METHODS: The SSVEPs to seven different frequencies of
      stimulation (4, 8, 17, 20, 23, 30 and 40Hz) were obtained from 18 schizophrenia
      subjects and 33 healthy control subjects. Power at stimulating frequency (signal
      power) and power at frequencies above and below the stimulating frequency (noise
      power) were used to quantify the SSVEP responses. RESULTS: Both groups showed an
      inverse relationship between power and frequency of stimulation. Schizophrenia
      subjects showed reduced signal power compared to healthy control subjects at
      higher frequencies (above 17Hz), but not at 4 and 8Hz at occipital region. Noise
      power was higher in schizophrenia subjects at frequencies between 4 and 20Hz over
      occipital region and at 4, 17 and 20Hz over frontal region. CONCLUSIONS: SSVEP
      signal power at beta and gamma frequencies of stimulation were reduced in
      schizophrenia. Schizophrenia subjects showed higher levels of EEG noise during
      photic stimulation at beta and lower frequencies. SIGNIFICANCE: Inability to
      generate or maintain oscillations in neural networks may contribute to deficits
      in visual processing in schizophrenia.

PMID- 15721077
TI  - Neural substrates of visual perceptual learning of simple and complex stimuli.
AB  - OBJECTIVE: The two experiments described here used event-related potentials
      (ERPs) to investigate whether perceptual learning of different complexities of
      stimuli involves different levels of visual cortical processing in human adults.
      METHODS: Reaction times and ERPs were recorded during 3 consecutive training
      sessions in which subjects discriminated between simple stimuli made of line
      segments or complex stimuli made of compound shapes. RESULTS: Reaction times in
      both experiments were shortened across training sessions. For simple stimuli,
      training resulted in a decreased N1 (125-155ms) and an increased P2 (180-240ms)
      over the occipital area. For complex stimuli, however, training resulted in a
      decreased N1 (125-155ms) and N2 (290-340ms) and an increased P3 (350-550ms) over
      the central/parietal areas. CONCLUSIONS: These findings suggest that perceptual
      learning modifies the response at different levels of visual cortical processing
      related to the complexity of the stimulus. SIGNIFICANCE: The neuronal mechanisms
      involved in perceptual learning may depend on the nature (e.g. the complexity) of
      the stimuli used in the discrimination task.

PMID- 15721078
TI  - Attention-deficit/hyperactivity disorder: cognitive evoked potential (P300)
      amplitude predicts treatment response to atomoxetine.
AB  - OBJECTIVE: Auditory cognitive evoked potential (P300) topography was reported to
      predict robust response to the stimulants pemoline and extended-release
      methylphenidate in patients with attention-deficit/hyperactivity disorder (ADHD).
      Patients with a right fronto-central to parietal auditory P300 amplitude ratio
      >0.5 respond robustly to stimulants, others do not. This exploratory study was
      performed to demonstrate whether the P300 predicts treatment response to the
      selective norepinephrine re-uptake inhibitor, atomoxetine. METHODS: Patients aged
      6-17 with DSM-IV diagnosis of ADHD were administered P300 testing. They then
      underwent open-label treatment with atomoxetine. Robust response was defined as a
      60% decrease from baseline in the ADHD rating scale (parent version, investigator
      rated). RESULTS: Ten of 17 subjects responded robustly. They did not differ from
      the non-robust responders in age, baseline attention or hyperactivity ratings, or
      any P300 parameter except 31-electrode mean auditory P300 amplitude (mean AA).
      Mean AA >6.8 microV predicted robust response with positive predictive value of
      0.88 and negative predictive value of 0.67. CONCLUSIONS: Mean AA seems to predict
      response to atomoxetine in patients with ADHD. SIGNIFICANCE: As non-stimulant
      treatments are approved for the treatment of ADHD, tests such as this may help
      pinpoint whether to use a stimulant or a medicine with some other mechanism of
      action.

PMID- 15721079
TI  - Developmental changes in refractoriness of the cortical auditory evoked
      potential.
AB  - OBJECTIVE: This study examined morphological changes in the cortical auditory
      evoked potential (CAEP) waveform as a function of varying stimulation rate.
      Stimuli were presented in a paradigm which indirectly assesses the refractory
      properties of the underlying neuronal generators. METHODS: CAEPs were recorded in
      50 normal-hearing children (3-12 years) and 10 young adults (24-26 years). A
      speech sound was presented in a stimulus train with sequentially decreasing inter
      stimulus intervals (ISIs) of 2000, 1000, 560, and 360ms. Latencies and amplitudes
      of the P1, N1, and P2 components at the Cz electrode were examined as a function
      of stimulus rate and age. RESULTS: Results revealed significant changes in the
      CAEP as a function of age and stimulation rate. At younger ages the N1-P2
      component was elicited only at the slowest stimulation rates, and was more
      clearly apparent at successively faster stimulation rates as age increased.
      CONCLUSIONS: We have described a stimulus paradigm that allows examination of the
      development of refractoriness by highlighting the interaction between age and
      rate on CAEP morphology. SIGNIFICANCE: Complex maturational patterns of CAEP
      components are best understood when the effects of both age and stimulus rate on
      the CAEP waveform are considered.

PMID- 15721080
TI  - Human auditory steady state responses to binaural and monaural beats.
AB  - OBJECTIVE: Binaural beat sensations depend upon a central combination of two
      different temporally encoded tones, separately presented to the two ears. We
      tested the feasibility to record an auditory steady state evoked response (ASSR)
      at the binaural beat frequency in order to find a measure for temporal coding of
      sound in the human EEG. METHODS: We stimulated each ear with a distinct tone,
      both differing in frequency by 40Hz, to record a binaural beat ASSR. As control,
      we evoked a beat ASSR in response to both tones in the same ear. We band-pass
      filtered the EEG at 40Hz, averaged with respect to stimulus onset and compared
      ASSR amplitudes and phases, extracted from a sinusoidal non-linear regression fit
      to a 40Hz period average. RESULTS: A 40Hz binaural beat ASSR was evoked at a low
      mean stimulus frequency (400Hz) but became undetectable beyond 3kHz. Its
      amplitude was smaller than that of the acoustic beat ASSR, which was evoked at
      low and high frequencies. Both ASSR types had maxima at fronto-central leads and
      displayed a fronto-occipital phase delay of several ms. CONCLUSIONS: The
      dependence of the 40Hz binaural beat ASSR on stimuli at low, temporally coded
      tone frequencies suggests that it may objectively assess temporal sound coding
      ability. The phase shift across the electrode array is evidence for more than one
      origin of the 40Hz oscillations. SIGNIFICANCE: The binaural beat ASSR is an
      evoked response, with novel diagnostic potential, to a signal that is not present
      in the stimulus, but generated within the brain.

PMID- 15721081
TI  - Auditory temporal processes in normal-hearing individuals and in patients with
      auditory neuropathy.
AB  - OBJECTIVE: To study objectively auditory temporal processing in a group of normal
      hearing subjects and in a group of hearing-impaired individuals with auditory
      neuropathy (AN) using electrophysiological and psychoacoustic methods. METHODS:
      Scalp recorded evoked potentials were measured to brief silent intervals (gaps)
      varying between 2 and 50ms embedded in continuous noise. Latencies and amplitudes
      of N100 and P200 were measured and analyzed in two conditions: (1) active, when
      using a button in response to gaps; (2) passive, listening, but not responding.
      RESULTS: In normal subjects evoked potentials (N100/P200 components) were
      recorded in response to gaps as short as 5ms in both active and passive
      conditions. Gap evoked potentials in AN subjects appeared only with prolonged gap
      durations (10-50ms). There was a close association between gap detection
      thresholds measured psychoacoustically and electrophysiologically in both normals
      and in AN subjects. CONCLUSIONS: Auditory cortical potentials can provide
      objective measures of auditory temporal processes. SIGNIFICANCE: The combination
      of electrophysiological and psychoacoustic methods converged to provide useful
      objective measures for studying auditory cortical temporal processing in normals
      and hearing-impaired individuals. The procedure used may also provide objective
      measures of temporal processing for evaluating special populations such as
      children who may not be able to provide subjective responses.

PMID- 15721082
TI  - The P50 midlatency auditory evoked potential in patients with chronic low back
      pain (CLBP).
AB  - OBJECTIVE: Patients with Chronic Low Back Pain (CLBP) show arousal, attentional
      and cognitive disturbances. The sleep state-dependent P50 midlatency auditory
      evoked potential was used to determine if patients with CLBP [with and without co
      morbid depression (DEP)] show quantitative disturbances in the manifestation of
      the P50 potential. METHODS: P50 potential latency, amplitude and habituation to
      repetitive stimuli at 250, 500 and 1000ms interstimulus intervals (ISIs) was
      recorded, along with the McGill Pain Questionnaire-Short Form (MPQ-SF). CLBP
      subjects (n=42) were compared with Controls (n=43), and with subjects with DEP
      only (n=6). Of the CLBP subjects, 20/42 had clinical depression (CLBP+DEP); 8/20
      were taking anti-depressant medication (CLBP+DEP+med), the others were not
      (CLBP+DEP-med). RESULTS: There were no differences (ANOVA) in age, sex or P50
      potential latency, although there was a trend towards increased latencies in CLBP
      groups. P50 potential amplitude was lower in CLBP groups, but not in sub-groups,
      again indicating a trend. P50 potential habituation was decreased in the DEP only
      subjects at the 250m ISI, and decreased in CLBP+DEP-med subjects at the 500ms
      ISI. This difference was not present in CLBP+DEP+med subjects. The MPQ-SF
      revealed that patients with CLBP and CLBP+DEP-med showed lower pain scores than
      CLBP+DEP+med patients. CONCLUSIONS: There is decreased habituation of the P50
      potential habituation in unmedicated patients with CLBP+DEP compared to Controls.
      SIGNIFICANCE: Patients with CLBP+DEP-med may be less able to disregard incoming
      sensory information, including painful sensations, but anti-depressant
      medications help correct this deficit. However, their perception of pain may be
      increased by medication.

PMID- 15721083
TI  - The evolutionary change of flash visual evoked potentials in preterm infants with
      periventricular leukomalacia.
AB  - OBJECTIVE: The aim of this study was to prospectively investigate flash visual
      evoked potential (VEP) findings and their chronological changes in preterm
      infants with cystic periventricular leukomalacia (PVL) during the early neonatal
      period. METHODS: The subjects of this study were 14 preterm infants with cystic
      PVL. The patients underwent serial cranial ultrasonography and diagnosed as
      having cystic PVL. Flash VEPs were diagnosed at least twice within the first 3
      weeks of life. RESULTS: All infants had at least one or more flash VEP
      abnormalities. The most common finding was 'absent VEP', which was seen in 13
      infants (93%). 'Delayed latency' was seen in two infants and 'abnormal waveform'
      was seen in one infant. Concerning the chronological changes, all records were
      abnormal in 4 infants, and the other 10 had transient normal VEP findings. Among
      them, flash VEPs changed from normal to abnormal within 10 days after birth in
      most cases. CONCLUSIONS: Almost all infants with cystic PVL had abnormal flash
      VEPs within the first 3 weeks of life, but chronological changes of flash VEP
      findings were seen during the period. SIGNIFICANCE: This manuscript may be useful
      as a reference to the flash VEPs in preterm infants with cystic PVL.

PMID- 15721084
TI  - Inter-rater reliability of sleep cyclic alternating pattern (CAP) scoring and
      validation of a new computer-assisted CAP scoring method.
AB  - OBJECTIVE: To assess inter-rater reliability between different scorers, from
      different qualified sleep research groups, in scoring visually the Cyclic
      Alternating Pattern (CAP), to evaluate the performances of a new tool for the
      computer-assisted detection of CAP, and to compare its output with the data from
      the different scorers. METHODS: CAP was scored in 11 normal sleep recordings by
      four different raters, coming from three sleep laboratories. CAP was also scored
      in the same recordings by means of a new computer-assisted method, implemented in
      the Hypnolab 1.2 (SWS Soft, Italy) software. Data analysis was performed
      according to the following steps: (a) the inter-rater reliability of CAP
      parameters between the four different scorers was carried out by means of the
      Kendall W coefficient of concordance; (b) the analysis of the agreement between
      the results of the visual and computer-assisted analysis of CAP parameters was
      also carried out by means of the Kendall W coefficient; (c) a 'consensus' scoring
      was obtained, for each recording, from the four scorings provided by the
      different raters, based on the score of the majority of scorers; (d) the degree
      of agreement between each scorer and the consensus score and between the computer
      assisted analysis and the consensus score was quantified by means of the Cohen's
      k coefficient; (e) the differences between the number of false positive and false
      negative detections obtained in the visual and in the computer-assisted analysis
      were also evaluated by means of the non-parametric Wilcoxon test. RESULTS: The
      inter-rater reliability of CAP parameters quantified by the Kendall W coefficient
      of concordance between the four different scorers was high for all the parameters
      considered and showed values above 0.9 for total CAP time, CAP time in sleep
      stage 2 and percentage of A phases in sequence; also CAP rate showed a high value
      (0.829). The most important global parameters of CAP, including total CAP rate
      and CAP time, scored by the computer-assisted analysis showed a significant
      concordance with those obtained by the raters. The agreement between the computer
      assisted analysis and the consensus scoring for the assignment of the CAP A phase
      subtype was not distinguishable from that expected from a human scorer. However,
      the computer-assisted analysis provided a number of false positives and false
      negatives significantly higher than that of the visual scoring of CAP.
      CONCLUSIONS: CAP scoring shows good inter-rater reliability and might be compared
      in different laboratories the results of which might also be pooled together;
      however, caution should always be taken because of the variability which can be
      expected in the classical sleep staging. The computer-assisted detection of CAP
      can be used with some supervision and correction in large studies when only
      general parameters such as CAP rate are considered; more editing is necessary for
      the correct use of the other results. SIGNIFICANCE: This article describes the
      first attempt in the literature to evaluate in a detailed way the inter-rater
      reliability in scoring CAP parameters of normal sleep and the performances of a
      human-supervised computerized automatic detection system.

PMID- 15721085
TI  - Disturbed fluctuations of resting state EEG synchronization in Alzheimer's
      disease.
AB  - OBJECTIVE: We examined the hypothesis that cognitive dysfunction in Alzheimer's
      disease is associated with abnormal spontaneous fluctuations of EEG
      synchronization levels during an eyes-closed resting state. METHODS: EEGs were
      recorded during an eyes-closed resting state in Alzheimer patients (N=24; 9
      males; mean age 76.3 years; SD 7.8; range 59-86) and non-demented subjects with
      subjective memory complaints (N=19; 9 males; mean age 76.1 years; SD 6.7; range:
      67-89). The mean level of synchronization was determined in different frequency
      bands with the synchronization likelihood and fluctuations of the synchronization
      level were analysed with detrended fluctuation analysis (DFA). RESULTS: The mean
      level of EEG synchronization was lower in Alzheimer patients in the upper alpha
      (10-13Hz) and beta (13-30Hz) band. Spontaneous fluctuations of synchronization
      were diminished in Alzheimer patients in the lower alpha (8-10Hz) and beta bands.
      In patients as well as controls the synchronization fluctuations showed a scale
      free pattern. CONCLUSIONS: Alzheimer's disease is characterized both by a lower
      mean level of functional connectivity as well as by diminished fluctuations in
      the level of synchronization. The dynamics of these fluctuations in patients and
      controls was scale-free which might point to self-organized criticality of neural
      networks in the brain. SIGNIFICANCE: Impaired functional connectivity can
      manifest itself not only in decreased levels of synchronization but also in
      disturbed fluctuations of synchronization levels.

PMID- 15721086
TI  - Electrical stimulation in epilepsy.

PMID- 15721087
TI  - Electrical brain-stimulation paradigm for estimating the seizure onset site and
      the time to ictal transition in temporal lobe epilepsy.
AB  - OBJECTIVE: To explore and validate a novel stimulation and analysis paradigm
      proposed to monitor spatial distribution and temporal changes of the excitability
      state in patients with temporal lobe epilepsy (TLE). METHODS: We use intermittent
      pulse stimulation in the frequency range 10-20Hz. A quantitative measure of
      spectral phase de-modulation, the relative phase clustering index (rPCI) was
      applied to the evoked EEG signals, measured from electrodes implanted in the
      hippocampal formation. RESULTS: We found that in the interictal periods, high
      values of rPCI recorded from specific sites were correlated with the most
      probable seizure onset sites (SOS). Furthermore we found that high values of rPCI
      from certain locations correlated with shorter time intervals to the next
      seizure. CONCLUSIONS: Our clinical findings indicate that although the precise
      moment of ictal transitions is in general unpredictable, it may be possible to
      estimate the probability of occurrence of some epileptic seizures. SIGNIFICANCE:
      The use of the rPCI for probabilistic forecasting of upcoming epileptic seizures
      is warranted. rPCI measurements may be used to guide interventions with the aim
      of modifying local tissue excitability that ultimately might prevent ictal
      transitions.

PMID- 15721088
TI  - EEG filtering based on blind source separation (BSS) for early detection of
      Alzheimer's disease.
AB  - OBJECTIVE: Development of an EEG preprocessing technique for improvement of
      detection of Alzheimer's disease (AD). The technique is based on filtering of EEG
      data using blind source separation (BSS) and projection of components which are
      possibly sensitive to cortical neuronal impairment found in early stages of AD.
      METHODS: Artifact-free 20s intervals of raw resting EEG recordings from 22
      patients with Mild Cognitive Impairment (MCI) who later proceeded to AD and 38
      age-matched normal controls were decomposed into spatio-temporally decorrelated
      components using BSS algorithm 'AMUSE'. Filtered EEG was obtained by back
      projection of components with the highest linear predictability. Relative power
      of filtered data in delta, theta, alpha 1, alpha 2, beta 1, and beta 2 bands were
      processed with Linear Discriminant Analysis (LDA). RESULTS: Preprocessing
      improved the percentage of correctly classified patients and controls computed
      with jack-knifing cross-validation from 59 to 73% and from 76 to 84%,
      correspondingly. CONCLUSIONS: The proposed approach can significantly improve the
      sensitivity and specificity of EEG based diagnosis. SIGNIFICANCE: Filtering based
      on BSS can improve the performance of the existing EEG approaches to early
      diagnosis of Alzheimer's disease. It may also have potential for improvement of
      EEG classification in other clinical areas or fundamental research. The developed
      method is quite general and flexible, allowing for various extensions and
      improvements.

PMID- 15721089
TI  - Standardizing and validating transcranial magnetic stimulation measures for use
      in stroke rehabilitation research.

PMID- 15721090
TI  - Plasma levels of N-terminal pro-brain natriuretic peptide in patients with
      coronary artery disease and relation to clinical presentation, angiographic
      severity, and left ventricular ejection fraction.
AB  - Comparative assessment of N-terminal pro-brain natriuretic peptide (NT-pro-BNP)
      across a wide spectrum of angiographic and clinical coronary artery disease (CAD)
      in a consecutive series of patients has not been reported. This study examined
      879 subjects (684 patients who had angiographically proved CAD and 195 controls
      who did not have CAD). NT-pro-BNP concentrations were measured before an
      angiographic procedure that allowed diagnosis of CAD and measurements of left
      ventricular ejection fraction and end-diastolic blood pressure. Median values
      (25th and 75th percentiles) of NT-pro-BNP in patients and controls were 474.5
      pg/ml (162.3 and 1,542.8) and 117.0 pg/ml (60.1 and 230.6), respectively (p
      <0.001). In patients who had stable angina, unstable angina, and acute myocardial
      infarction, NT-pro-BNP concentrations were 327.7 pg/ml (129.2 and 973.2), 660.6
      pg/ml (201.2 and 1,563.5), and 1,045.0 pg/ml (323.8 and 2,486.0, p <0.001). NT
      pro-BNP concentrations in subgroups with 1-, 2-, and 3-vessel CAD were 385.5
      pg/ml (117.2 and 1,266.0), 463.0 pg/ml (135.0 and 1,480.5), and 533.8 pg/ml
      (221.8 and 1,809.4), respectively (p = 0.005). Multivariable analysis showed that
      NT-pro-BNP was an independent correlate of the presence of CAD (chi-square 10.8,
      odds ratio 1.08, 95% confidence interval 1.03 to 1.13 for 100-pg/ml increase in
      concentration; p <0.001), acute coronary syndromes (chi-square 6.3, odds ratio
      1.01, 95% confidence interval 1.00 to 1.02 for 100-pg/ml increase in
      concentration, p = 0.01) and a strong trend that was independently associated
      with angiographic severity (chi-square 3.68, p = 0.055). This study shows that NT
      pro-BNP concentrations are high across the entire spectrum of CAD and parallel
      the clinical or angiographic severity of CAD.

PMID- 15721091
TI  - Impact of nonfatal myocardial infarction on outcomes in patients with advanced
      heart failure and the effect of bucindolol therapy.
AB  - We sought to identify the clinical characteristics and outcomes of patients who
      had advanced heart failure and nonfatal myocardial infarction (MI) in the beta
      Blocker Evaluation of Survival Trial (BEST) and to investigate whether bucindolol
      alters the risk of developing nonfatal MI. Of the 2,708 patients enrolled in the
      study, 142 had suspected MI and 69 had confirmed MI; there were 860 deaths
      overall. The rate of nonfatal MI in the BEST was low over the 4.1 years of follow
      up (4.8% had suspected events and 2.4% had adjudicated events) and was similar to
      that in high-risk populations. Cox's proportional hazard model with 23
      prespecified candidate variables associated advanced age, heart failure symptoms,
      male gender, ischemic etiology, diabetes, and hypertension with nonfatal MI or
      cardiovascular death. The 2-year mortality rate was 56% for the cohort that had
      suspected nonfatal MI versus 30% for the cohort that did not (p = 0.01).
      Likewise, the risk of hospitalization for congestive heart failure was twofold
      greater. Beta-blocker therapy with bucindolol resulted in a 52% decrease in
      suspected nonfatal MI (2.9% vs 5.5%, p = 0.001). In conclusion, nonfatal MI
      occurs at low rates but increases the risks for mortality and hospitalization in
      patients who have advanced heart failure. Beta-blocker therapy with bucindolol
      appears to attenuate the risk of nonfatal MI in this population.

PMID- 15721092
TI  - Comparison of low-mechanical index pulse sequence schemes for detecting
      myocardial perfusion abnormalities during vasodilator stress echocardiography.
AB  - Myocardial contrast echocardiography has the potential to accurately detect
      functionally significant coronary artery disease during pharmacologic stress
      testing. Different low-mechanical index modalities, including triggering
      replenishment imaging (TRI) and real-time imaging (RTI), are currently used to
      identify myocardial perfusion defects. We compared the ability of TRI with that
      of RTI for detecting and localizing perfusion abnormalities. Thirty-six patients
      (62 +/- 14 years old, 15 men) underwent single-photon emission computed
      tomography (SPECT) with technetium-99m sestamibi and myocardial contrast
      echocardiography at baseline and after infusion of 0.56 mg/kg of dipyridamole.
      Sixteen of these patients also underwent quantitative angiography. Contrast
      enhanced images were obtained in 4-, 3-, and 2-chamber views after intravenous
      bolus injections of lipid-encapsulated microbubbles (0.1 ml of Definity). A
      myocardial perfusion defect was defined by myocardial contrast echocardiography
      as a delay of >2 seconds in contrast replenishment after high-mechanical index
      flash impulse. The myocardial segments were divided into 3 major coronary
      territories. There was agreement in detecting perfusion defects between SPECT and
      TRI in 26 patients (72%, kappa = 0.46) and between SPECT and RTI in 27 patients
      (75%, kappa = 0.50). Agreements between myocardial contrast echocardiography and
      SPECT for localizing coronary territories with perfusion defects were 81% for TRI
      (kappa = 0.43) and 85% for RTI (kappa = 0.61). Accuracy of RTI for detecting >50%
      diameter stenoses by quantitative angiography was 79%, that of TRI was 71%, and
      that of SPECT was 65%. These data indicate that the different low-mechanical
      index imaging schemes are equivalent to radionuclide SPECT in accurately
      detecting diseased coronary artery territories during vasodilator stress.

PMID- 15721093
TI  - Noninvasive coronary imaging and assessment of left ventricular function using 16
      slice computed tomography.
AB  - In recent years, multislice computed tomography (MSCT) has been demonstrated to
      be a feasible imaging modality for noninvasive coronary angiography and left
      ventricular function analysis. The present study evaluated overall performance of
      16-slice MSCT in the detection of significant coronary artery disease, stent, or
      bypass graft stenosis in combination with global left ventricular function
      analysis. Forty-five patients underwent 16-slice MSCT. Multislice computed
      tomograms were used to evaluate the presence of significant coronary artery
      stenoses (>/=50% decrease in luminal diameter) in native coronary segments,
      bypass grafts, and coronary stents and were compared with conventional coronary
      angiograms. In addition, left ventricular ejection fraction was calculated and
      compared with 2-dimensional echocardiography. MSCT was performed successfully in
      all patients. A close correlation between MSCT and 2-dimensional echocardiography
      was demonstrated for the assessment of left ventricular ejection fraction (y =
      0.93x +3.33, r = 0.96, p <0.001). A total of 298 of native coronary artery
      segments (94%) were evaluated with MSCT, whereas 81 of 94 grafts (85%) and 41 of
      52 coronary stents (79%) were also evaluated. For all segments, overall
      sensitivity, specificity, and positive and negative predictive values were 85%,
      89%, 71%, and 95%, respectively. In conclusion, 16-slice MSCT is a feasible
      modality for noninvasive evaluation and exclusion of coronary artery disease in
      patients who present with chest pain.

PMID- 15721094
TI  - Usefulness of noncoronary vascular disease in predicting adverse events in the
      year following percutaneous coronary intervention.
AB  - It is unknown whether noncoronary vascular disease is associated with persistent
      cardiac risk in patients who undergo percutaneous coronary intervention (PCI).
      Using the National Heart, Lung, and Blood Institute Dynamic Registry, the
      incidence of death, myocardial infarction (MI), and repeat revascularization
      outcomes were compared in patients who had noncoronary vascular disease (n = 554)
      with patients who did not (n = 4,075). Vascular disease was defined as a history
      of stroke, transient ischemic attack, claudication, vascular bypass, limb
      amputation, or aortic aneurysm. Patients who had concomitant noncoronary vascular
      disease had more significant co-morbidities. Angiographic success rate was lower
      in patients who had concomitant noncoronary vascular disease (89.5% vs 93.2%, p
      <0.01), whereas in-hospital adverse events, including death (2.7% vs 1.3%, p
      <0.05), MI (4.7% vs 2.6%, p <0.01), stroke (1.1% vs 0.2%, p <0.001), major entry
      site complication (6.7% vs 3.5%, p <0.001), and need for coronary artery bypass
      grafting (2.2% vs 1.1%, p <0.05) were significantly higher. One-year death rate
      (10.5% vs 4.5%, p <0.001) and MI rate (9.2% vs 5.2%, p <0.001) were also
      significantly higher in patients who had vascular disease. After adjustment,
      vascular disease was independently associated with a higher risk of death or MI
      (risk ratio 1.4, 95% confidence interval 1.1 to 1.8) and death, MI, or coronary
      artery bypass grafting (risk ratio 1.3, 95% confidence interval 1.1 to 1.6) at 1
      year. Repeat PCI rates were similar (15.9% vs 13.8%, p = NS). In conclusion, the
      presence of noncoronary vascular disease is an independent predictor of MI and
      death or MI 1 year after PCI. Because PCI is often performed before vascular
      surgery, these data may lend insight to the risk/benefit ratio of such an
      approach.

PMID- 15721095
TI  - Bivalirudin versus heparin and glycoprotein IIb/IIIa inhibition among patients
      with renal impairment undergoing percutaneous coronary intervention (a
      subanalysis of the REPLACE-2 trial).
AB  - Among patients who undergo percutaneous coronary intervention, renal impairment
      is associated with an excessive risk of bleeding and ischemic events. Bivalirudin
      provides comparable suppression of ischemic events with a decrease in bleeding
      events compared with heparin and glycoprotein IIb/IIIa inhibition. We examined
      the relation between adverse events, renal impairment, and antithrombotic therapy
      within a randomized comparison. The Second Randomized Evaluation in PCI Linking
      Bivalirudin to Reduced Clinical Events per-protocol study population was
      assessed. Renal function was defined as calculated creatinine clearance <60
      ml/min. Events within the overall study population and within each study arm were
      assessed. Thirty-day events by renal function were compared by chi-square test
      and logistic regression. Late mortality was compared by log-rank test.
      Interaction analyses were performed. Among 5,710 patients, renal impairment was
      associated with increased ischemic events (hazard ratio 1.45, 95% confidence
      interval 1.13 to 1.88, p = 0.004), bleeding complications (hazard ratio 1.72, 95%
      confidence interval 1.06 to 2.80, p = 0.028), and excessive 12-month mortality
      (hazard ratio 3.85, 95% confidence interval 2.67 to 5.54, p <0.001). Bivalirudin
      provided suppression of ischemic events that was comparable to heparin and
      glycoprotein IIb/IIIa inhibition regardless of renal impairment. Fewer bleeding
      events with bivalirudin were also evident irrespective of renal dysfunction. No
      interaction between treatment assignment, bleeding or ischemic complications, and
      renal impairment was observed. The safety and efficacy of bivalirudin compared
      with heparin and planned glycoprotein IIb/IIIa inhibition in this high-risk group
      are comparable and consistent with the results of the overall trial.

PMID- 15721096
TI  - Impact of dyslipidemia associated with Highly Active Antiretroviral Therapy
      (HAART) on cardiovascular risk and life expectancy.
AB  - We investigated the effect of dyslipidemia associated with highly active
      antiretroviral therapy on cardiovascular risk and life expectancy among patients
      who had the human immunodeficiency virus. Dyslipidemia estimates were based on
      results from a phase 2 randomized trial that compared lipid changes after 32
      weeks of therapy with atazanavir with those with nelfinavir (each in combination
      with stavudine and lamivudine). The resultant increased coronary risk was
      estimated using Framingham risk equations, and change in life expectancy (after
      adjustment for mortality due to human immunodeficiency virus) was based on the
      cardiovascular life expectancy model, which is based on a published Markov's
      model. Levels of total cholesterol and low-density lipoprotein cholesterol
      increased significantly more among patients who used nelfinavir (+24% and +28%)
      than among those who used atazanavir (+4% and +1%). This dyslipidemia increased
      the risk of coronary disease by 50% over 10 years. The absence of dyslipidemia
      was estimated to preserve life expectancy 0.15 to 1.53 additional years depending
      on a patient's age, gender, and other risk factors. There are increasing reports
      of dyslipidemia and cardiovascular events associated with highly active
      antiretroviral therapy. Significant increases in blood lipid levels observed with
      some protease inhibitors are associated with an increase in calculated 10-year
      coronary risk. Accordingly, minimizing dyslipidemia associated with highly active
      antiretroviral therapy may preserve life expectancy among adults who have the
      human immunodeficiency virus.

PMID- 15721097
TI  - Comparison of transesophageal echocardiographic identification of embolic risk
      markers in patients with lone versus non-lone atrial fibrillation.
AB  - Although transesophageal echocardiographically derived parameters, notably
      spontaneous echocardiographic contrast (SEC) in the left atrium or left atrial
      appendage (LAA), are known predictors of embolism in atrial fibrillation, their
      value is less well known in patients who have lone atrial fibrillation (LAF).
      This study describes transesophageal echocardiographic findings and identifies
      clinical predictors of SEC in the left atrium or LAA in a cohort of patients who
      had LAF. Eighty-two patients who had LAF and 289 patients who had non-LAF and
      underwent transesophageal echocardiography were enrolled from July 1998 to March
      2002. LAA abnormality was defined as the presence of an LAA area >5 cm(2),
      emptying or filling LAA velocities <25 cm/s, or the presence of SEC or thrombus
      in the left atrium or LAA; LAA abnormalities were significantly less frequent in
      patients who had LAF than in those who had non-LAF. SEC in the left atrium or LAA
      was significantly less frequent in patients who had LAF than in those who had non
      LAF (29.3% vs 49.8%, respectively, p <0.001). In patients who had LAF, SEC in the
      left atrium or LAA was significantly (p <0.05) less frequent in patients who were
      </=60 years old (17.9%) than in patients who were >60 years old (39.5%) and in
      patients who had paroxysmal LAF (5.9%) than in those who had persistent LAF
      (45.8%). On multivariate analysis, age and persistent LAF were the only clinical
      variables independently associated with SEC. Thus, transesophageal
      echocardiography detects thromboembolism risk markers in patients who have LAF.
      These abnormalities are less frequent in patients who have LAF than in those who
      are at low risk and have non-LAF; however, in patients who have LAF, older age
      and persistent atrial fibrillation are associated with these risk markers.

PMID- 15721099
TI  - Contribution of left ventricular diastolic dysfunction to heart failure
      regardless of ejection fraction.
AB  - Heart failure (HF) has been classified as systolic and diastolic based on the
      left ventricular ejection fraction. We hypothesized that left ventricular
      diastolic dysfunction is an important element of HF regardless of ejection
      fraction. Two hundred six patients who had clinical HF were compared with 72 age
      matched controls. Diastolic dysfunction, as assessed by the mitral filling
      pattern and tissue Doppler imaging, was present in >90% of patients who had HF
      regardless of ejection fraction and was more frequent and severe than in age
      matched controls (p <0.001). In patients who had HF, B-type natriuretic peptide
      correlated with diastolic dysfunction (r = 0.62, p <0.001) but not with ejection
      fraction or end-diastolic volume index (EDVI). The degree of diastolic
      dysfunction influenced survival rate (risk ratio 1.64, p <0.05), whereas ejection
      fraction and EDVI did not. Systolic function measured by systolic mitral annular
      velocity was decreased in patients who had HF and an ejection fraction </=0.40
      (4.8 +/- 1.1 cm/s) and, to a lesser extent, an ejection fraction >/=0.50 (6.6 +/-
      1.8 cm/s) compared with control subjects (8.0 +/- 2.1 cm/s, p <0.01). Patients
      who had HF and an ejection fraction >/=0.50 had an increased ratio of ventricular
      mass to EDVI. Patients who had HF and an ejection fraction </=0.40 had increased
      left ventricular EDVI. Thus, regardless of ejection fraction, patients who have
      HF also have diastolic dysfunction. Diastolic dysfunction is a better predictor
      of B-type natriuretic peptide levels and mortality than ejection fraction or left
      ventricular EDVI. In addition to diastolic dysfunction, HF with an ejection
      fraction >/=0.50 is associated with mild systolic dysfunction and an increased
      ratio of left ventricular mass to EDVI. In HF with an ejection fraction </=0.40,
      systolic dysfunction and left ventricular dilation accompany diastolic
      dysfunction.

PMID- 15721098
TI  - Relation of initial resting ventricular rate to the ability to achieve and
      maintain normal sinus rhythm in patients with atrial fibrillation.
AB  - Rate-control and rhythm-control strategies in the management of atrial
      fibrillation (AF) have been shown to have similar effects on morbidity and
      mortality. Data are lacking as to whether specific electrocardiographic features
      of AF affect the ability to achieve rate or rhythm control. This study evaluated
      the relation between initial resting ventricular rate (IRVR) during AF and the
      subsequent achievement of rate control and rhythm control in the AFFIRM Study.
      The independent relations between IRVR and the achievement of rate and rhythm
      control were assessed using multivariate Cox's proportional hazards modeling. In
      addition, we evaluated whether IRVR was associated with major cardiovascular end
      points. IRVR was analyzed in 4,059 patients. IRVR was higher in women, smokers,
      patients who had a first episode of AF, and in patients who had preserved left
      ventricular systolic function but lower in patients who had coronary artery
      disease, hypertension, left atrial enlargement, and a qualifying episode of AF
      that lasted >48 hours. A higher IRVR was independently associated with the
      achievement (p <0.0001) and maintenance (p = 0.0002) of sinus rhythm, whereas the
      ability to achieve adequate rate control was independent of IRVR. A higher IRVR
      was associated with an increased risk of cardiovascular hospitalization (p
      <0.0001). In the appropriate clinical setting, a rhythm-control strategy should
      be considered for patients who have a higher IRVR.

PMID- 15721100
TI  - Echocardiographic differentiation of atrioventricular septal defects from inlet
      ventricular septal defects and mitral valve clefts.
AB  - Left ventricular inlet/outlet ratio and percent left atrioventricular valve (AVV)
      guarded by the posterior leaflet are valuable for characterizing atrioventricular
      septal defect (AVSD). We performed these measurements echocardiographically in
      normal patients (n = 101), patients who had AVSD (n = 37), those who had isolated
      perimembranous inlet ventricular septal defect (VSD; n = 12), and those who had
      "isolated" mitral valve clefts (n = 5). Surgical findings of 38 patients were
      reviewed. The normal inlet/outlet ratio was 1.03 +/- 0.07. For patients who had
      AVSD, the ratio was 0.82 +/- 0.06 (95% confidence interval [CI] 0.180 to 0.237, p
      = 0.001). For patients who had an isolated inlet VSD, this ratio was lower than
      that in normal patients (0.93 +/- 0.08, 95% CI 034 to 0.116, p = 0.001) but
      higher than that in patients who had AVSD (95% CI -0.175 to 0.091, p = 0.001).
      The percent left AVV guarded by the posterior leaflet was 56 +/- 1.4 in normal
      patients. For patients who had AVSD, it was significantly lower (43 +/- 1.1). For
      patients who had an isolated VSD and those who had an isolated mitral cleft, it
      was normal (57 +/- 1.9 and 55 +/- 2.2, respectively). The 2 measurements are
      valuable in differentiating AVSD from inlet VSD and isolated mitral cleft, but
      percent left AVV guarded by the posterior leaflet is more specific.

PMID- 15721101
TI  - Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein
      IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical
      trials).
AB  - We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy
      with stand-alone fibrinolysis with respect to speed and stability of reperfusion
      in patients who had acute ST-segment elevation myocardial infarction; data were
      obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation
      to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation
      Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial
      Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the
      Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared
      thrombolytics plus lamifiban, eptifibatide, or abciximab with standard
      thrombolysis. We found significantly faster and more stable ST-segment recovery
      with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST
      segment resolution, p = 0.03) and sustained over 180 minutes after drug
      administration; this transient benefit may suggest a time frame when more optimal
      percutaneous coronary intervention can be performed.

PMID- 15721102
TI  - Prognostic usefulness of white blood cell count and temperature in acute
      myocardial infarction (from the CARDINAL Trial).
AB  - White blood cell (WBC) count and temperature are 2 global measures of
      inflammation that are systematically gathered and easily identifiable in a
      clinical setting, unlike many other markers of inflammation being investigated in
      patients with coronary artery disease. The prognostic usefulness of the WBC count
      and temperature were evaluated in a large acute myocardial infarction trial, the
      Complement And ReDuction of INfarct size after Angioplasty or Lytics program.
      Baseline and serial measurements of WBC counts and temperature were correlated
      with infarct size and clinical outcome.

PMID- 15721103
TI  - Prognostic significance of simvastatin therapy in patients with ischemic heart
      failure who underwent percutaneous coronary intervention for acute myocardial
      infarction.
AB  - We prospectively followed 202 patients with ischemic heart failure who underwent
      percutaneous coronary intervention (PCI) for acute myocardial infarction (left
      ventricular [LV] ejection fraction <40%). Patients were divided into 2 groups:
      groups I (simvastatin group, n = 106, aged 60.8 +/- 10.3 years, men 71.7%) and II
      (non-simvastatin group, n = 96, aged 60.9 +/- 10.4 years, men 78.1%). During 1
      year clinical follow-up, simvastatin therapy was associated with a significant
      reduction in mortality (1.9% vs 7.5%, p = 0.048), restenosis rate (25.7% vs
      43.1%, p = 0.033), and repeat PCI rate (25.7% vs 43.1%, p = 0.033), and with
      significant improvement in LV ejection fraction (31% to 42% vs 32% to 39%, p =
      0.042). The event-free survival rate was higher in group I than in group II
      (79.8% vs 57.0%, p = 0.001). In conclusion, simvastatin therapy improves LV
      systolic function and decreases mortality, restenosis, and repeat PCI rate in
      patients with ischemic heart failure who underwent PCI for acute myocardial
      infarction.

PMID- 15721104
TI  - Comparison of the cardioprotective effect of prodromal angina pectoris and
      collateral circulation in patients with a first anterior wall acute myocardial
      infarction.
AB  - To compare the cardioprotective effect of prodromal angina pectoris and
      collateral circulation, 245 patients with first anterior acute myocardial
      infarction who underwent coronary angioplasty within 12 hours of symptoms were
      studied. Prodromal angina pectoris and collateral circulation were independently
      associated with higher predischarge left ventricular ejection fraction (LVEF),
      and a combination of prodromal angina pectoris and collateral circulation
      afforded cumulative improvement in LVEF in patients without diabetes mellitus. In
      patients with diabetes mellitus, collateral circulation, but not prodromal angina
      pectoris, was associated with higher predischarge LVEF.

PMID- 15721105
TI  - Relation of echocardiographic left ventricular mass, geometry and wall stress,
      and left atrial dimension to coronary calcium in young adults (the CARDIA study).
AB  - We examined the relation of measures of echocardiographic left ventricular mass
      and geometry with coronary artery calcium (CAC) in 2,724 young adults. After
      adjustment for other coronary risk factors, left atrial dimension remained
      associated with the presence of CAC, and among subjects positive for CAC, left
      ventricular mass, end-systolic stress, and septal and posterior wall thicknesses
      in diastole remained associated with an increased extent of CAC.

PMID- 15721106
TI  - Safety of coronary stenting with eptifibatide and ultra-low-dose heparin.
AB  - With the advent of multiple potent antiplatelet and anticoagulation agents in
      percutaneous coronary intervention (PCI), the risk of bleeding complications has
      increased. The optimal dose of unfractionated heparin in this setting is unclear.
      This study was designed to determine the feasibility and safety of PCI with an
      ultra-low-dose weight-adjusted unfractionated heparin regimen (30 IU/kg bolus,
      maximum 3,000 IU) in combination with aspirin, clopidogrel, and eptifibatide. We
      enrolled 83 patients who underwent nonemergency PCI of native coronary arteries.
      At 30 days, all patients were free of the primary clinical outcomes defined as a
      composite of death, myocardial infarction, or repeat target vessel
      revascularization, and there were no major bleeding complications.

PMID- 15721108
TI  - Fate of unprotected side branches as related to embolic complications during
      stent implantation for acute coronary syndromes using a distal protection
      procedure.
AB  - Coronary lesion stenting with aspiration and distal balloon occlusion is more
      often associated with embolic occlusion of interposed side branches when the
      branch arises at an angle of </=45 degrees and the artery containing the lesion
      is large. However, this event is infrequent, often resolving during the procedure
      and uniformly resolving by 6 months.

PMID- 15721107
TI  - Relation of CD39 to plaque instability and thrombus formation in directional
      atherectomy specimens from patients with stable and unstable angina pectoris.
AB  - To determine whether the expression of CD39 in coronary atherosclerotic lesions
      is related to plaque instability and thrombus formation, we assessed directional
      coronary atherectomy (DCA) specimens from patients with stable and unstable
      angina pectoris. CD39 immunoreactivity was decreased in culprit lesions in
      patients with unstable angina pectoris compared with those with stable angina
      pectoris, and was reduced in DCA specimens with thrombus formation. These results
      suggest that CD39 expressed in atheromatous plaque plays an important role in
      preventing acute coronary syndromes.

PMID- 15721109
TI  - Meta-analysis comparing drug-eluting stents with bare metal stents.
AB  - We performed a meta-analysis of 10 randomized trials of 5,066 patients with 6 to
      12 months of follow-up. The summary risk differences excluded any major
      differences between the 2 types of stents for death (0.12%, 95% confidence
      interval [CI] -0.34% to 0.58%, p = 0.60) and overall myocardial infarction
      (0.04%, 95% CI -0.72% to 0.81%, p = 0.91). There was a modest increase in the
      risk of Q-wave myocardial infarction with drug-eluting stents (0.36%, 95% CI 
      0.04% to 0.77%, p = 0.080) but no difference in non-Q-wave myocardial infarction
      (-0.26%, 95% CI -0.95% to 0.43%, p = 0.47). The trend for increased risk of Q
      wave myocardial infarction was seen for paclitaxel and sirolimus stents (risk
      differences 0.28% and 0.58%, respectively). Drug-eluting stents also had a
      nonsignificant trend for higher risk of thrombosis (0.29%, 95% CI -0.08% to
      0.66%, p = 0.13). We conclude that sirolimus- and paclitaxel-eluting stents are
      equivalent to bare-metal stents in terms of mortality and overall myocardial
      infarction risk for the first year of follow-up; the meta-analysis excludes with
      considerable confidence the presence of large, clinically relevant differences
      for these outcomes.

PMID- 15721111
TI  - Comparison of left ventricular diastolic function after on-pump versus off-pump
      coronary artery bypass grafting.
AB  - We evaluated diastolic function in patients who underwent elective
      revascularization by standard on-pump coronary artery bypass graft (CABG) surgery
      versus off-pump CABG. Diastolic function improved in both groups, but indexes of
      early diastolic filling and myocardial relaxation improved more in patients who
      underwent on-pump than off-pump CABG.

PMID- 15721110
TI  - Comparison of early outcome of percutaneous coronary intervention for unprotected
      left main coronary artery disease in the drug-eluting stent era with versus
      without intravascular ultrasonic guidance.
AB  - The aim of this study was to assess the short- and mid-term clinical impact of
      intravascular ultrasound guidance in 58 patients referred for elective
      percutaneous treatment of unprotected left main coronary artery disease with drug
      eluting stents. The use of intravascular ultrasound, used in 41% of the
      procedures, was not associated with additional clinical benefit with respect to
      angiographic-assisted stent deployment.

PMID- 15721112
TI  - Influence of vessel diameter on the efficacy of distal protection devices during
      saphenous vein graft intervention.
AB  - We sought to determine the influence of vessel diameter on the efficacy of distal
      protection devices during saphenous vein graft intervention. From the Filterwire
      EX Randomized Evaluation trial, in which patients who underwent saphenous vein
      graft stenting were randomized to distal protection with the GuardWire or
      FilterWire EX, outcomes in 572 patients were examined in vessel size tertiles.
      The 30-day composite incidence of major adverse cardiac events (MACEs) increased
      with vessel size and was 6.9%, 9.7%, and 14.9% in the smallest, middle, and
      largest tertiles, respectively (p = 0.04). MACE rates were relatively vessel size
      independent for the GuardWire but increased steadily with vessel size with the
      FilterWire EX. In the smallest tertile, MACEs were reduced by 71% with the
      FilterWire EX compared with the GuardWire (p = 0.05), with the devices showing
      similar event rates in the other tertiles.

PMID- 15721113
TI  - Relation of family history of premature coronary heart disease and metabolic risk
      factors to risk of coronary arterial calcium in asymptomatic subjects.
AB  - We studied 6,141 consecutive, asymptomatic, nondiabetic patients who underwent
      electron beam tomography and explored the interaction between metabolic risk
      factors (RFs) and premature family history (FH) of coronary heart disease (CHD)
      in predicting the presence and severity of coronary arterial calcium (CAC). In
      the presence of >2 metabolic RFs, patients with a positive FH of premature CHD
      had a significantly higher prevalence of any CAC, CAC >/=100, and CAC >/=75th age
      gender percentile than those without a FH of CHD. Our study demonstrated that a
      familial propensity to subclinical atherosclerosis interacts with the presence of
      >/=2 metabolic RFs, magnifying the risks for those exposed to both.

PMID- 15721114
TI  - Safety of perioperative statin use in high-risk patients undergoing major
      vascular surgery.
AB  - No clinical data are available on the influence of perioperative statin use on
      postoperative myopathy in patients undergoing major noncardiac surgery except for
      some case reports. Therefore, the aim of this study was to clarify the potential
      risk of myopathy in statin users who underwent major noncardiac surgery.

PMID- 15721115
TI  - Tissue tracking imaging as a new modality for identifying the origin of
      idiopathic ventricular arrhythmias.
AB  - Tissue tracking imaging was performed in 33 patients with idiopathic ventricular
      arrhythmias before radiofrequency catheter ablation. The site of the arrhythmia
      origin, defined as the site where the earliest color-coded signal appeared on the
      myocardium at the onset of the arrhythmia, corresponded to the site of origin as
      determined on fluoroscopy during activation mapping in all patients. Catheter
      ablation at that site abolished the arrhythmia in 29 patients (88%).

PMID- 15721116
TI  - Time to resumption of driving after implantation of an automatic defibrillator
      (from the Dual chamber and VVI Implantable Defibrillator [DAVID] trial).
AB  - The time to resumption of driving after insertion of an implantable cardioverter
      defibrillator (ICD) was evaluated in the Dual Chamber And VVI Implantable
      Defibrillator trial. Most patients were advised not to drive for 3 to 6 months
      after the ICD was implanted. Patients were surveyed at 3-, 6-, or 9-month
      intervals to characterize their driving habits, with 101 of 137 (73.7%), 98 of
      146 (67.1%), and 79 of 135 (58.5%) responding. Of respondents, 82% recalled being
      told not to drive for a specified time after ICD implantation. These patients
      generally obeyed recommendations (association between recommended time and time
      of resumption, p <0.001) from medical personnel.

PMID- 15721117
TI  - Interatrial block as a predictor of embolic stroke.
AB  - Interatrial block (IAB), defined as a prolonged (>/=110 ms) P wave, is remarkably
      prevalent in general hospital populations and is associated with an enlarged,
      poorly contractile left atrium. The investigators sought to determine whether
      there is an increased incidence of IAB in patients with embolic strokes.
      Patients' medical records were reviewed for evidence of embolic cerebrovascular
      events and IAB. One hundred four patients were identified. In 61 patients in
      normal sinus rhythm, 49 (80%) had IAB. This was almost twice the prevalence of 2
      previous studies (41% and 47%). Therefore, IAB may represent a new risk factor
      for stroke.

PMID- 15721118
TI  - Direct medical costs of syncope-related hospitalizations in the United States.
AB  - Little is known about the costs of syncope-related admissions in the United
      States. A nationally representative sample of hospital discharges and reported
      charges was analyzed, and costs were estimated using Medicare cost-to-charge
      ratios. A conservative estimate of total annual costs for syncope-related
      hospitalizations was $2.4 billion (95% confidence interval [CI] $2.2 to $2.6
      billion), with a mean cost of $5,400 (95% CI $5,100 to $5,600) per
      hospitalization. Efforts to safely decrease syncope-related admissions may result
      in substantial costs savings.

PMID- 15721119
TI  - Permanent pacing is a risk factor for the development of heart failure.
AB  - No previous study has examined the importance of right ventricular pacing as a
      risk factor for the development of heart failure (HF) in subjects without a
      history of HF. A cohort study of patients who underwent initial pacemaker
      implantation (n = 11,426) was conducted to test the hypothesis that patients with
      ventricular dyssynchrony created by permanent pacing would develop HF, as shown
      by new HF hospitalizations or HF-related deaths, at a higher rate than matched
      controls.

PMID- 15721120
TI  - Effects of varying ethanol dosing in percutaneous septal ablation for obstructive
      hypertrophic cardiomyopathy on early hemodynamic changes.
AB  - This prospective, randomized study evaluates the association between ethanol dose
      and postprocedural hemodynamic changes in 42 patients treated by alcohol septal
      ablation for obstructive hypertrophic cardiomyopathy. These results suggest that
      the early course of hemodynamic changes is not related to the use of a small (1
      to 2 ml) or standard (>2 ml) dose of ethanol.

PMID- 15721121
TI  - Usefulness of real-time navigator magnetic resonance imaging for evaluating
      coronary artery origins in pediatric patients.
AB  - Navigator coronary magnetic resonance imaging (MRI) was evaluated in assessing
      coronary artery origins in a pediatric and adolescent population. Sixty-five
      consecutive infants, children, or adolescents (age range 11 days to 21 years)
      were referred for MRI evaluations to assess coronary artery origins. Coronary
      artery origins were unambiguously delineated in 62 of 65 patients. In 3 patients,
      irregular arrhythmias precluded cardiac gating of the magnetic resonance
      acquisition. Two patients had anomalous coronary artery origins detected. Twenty
      six patients required sedation for the studies. Free-breathing 3-dimensional MRI
      with real-time navigator correction is a robust method for delineating the
      coronary artery origins in pediatric and adolescent patients.

PMID- 15721122
TI  - Usefulness of multidetector row computed tomography to quantify right ventricular
      size and function in adults with either tetralogy of Fallot or transposition of
      the great arteries.
AB  - An ever-increasing number of patients with congenital heart disease are reaching
      adulthood; follow-up often requires right ventricular (RV) quantification.
      Complex anatomy, acoustic window, and active implants such as pacemakers may
      limit modalities, such as echocardiography and cardiac magnetic resonance imaging
      (MRI), in this population. Recent advances in multidetector row cardiac computed
      tomography (MDCT) allow multiphase, multislice reconstructions in any plane but
      have not been applied to RV quantification. Fourteen patients with tetralogy of
      Fallot or transposition of the great arteries underwent cardiac MRI and MDCT
      examinations, with comparable quantification of RV volumes and ejection fractions
      and no systematic error by Bland-Altman analysis using MRI as the gold standard.

PMID- 15721123
TI  - Effect of acute changes in load on left ventricular diastolic function during
      device closure of atrial septal defects.
AB  - Echocardiographic indexes of left ventricular (LV) diastolic function were
      assessed in 18 patients before and after device closure of secundum atrial septal
      defects. The tissue Doppler early diastolic peak annular velocity (Ea) and color
      M-mode velocity of propagation (Vp), indexes of relaxation, seemed to be load
      independent and were not affected by the change in LV filling hemodynamics,
      whereas the mitral inflow peak E-wave velocity and E/Ea ratio were more load
      dependent, with a resultant increase after the closure of large atrial shunts.

PMID- 15721124
TI  - Effects of metallic implants on magnetic resonance imaging evaluation of Fontan
      palliation.
AB  - This study examined the effects of endovascular metallic implants on the ability
      of magnetic resonance imaging to evaluate cardiovascular anatomy and to assess
      ventricular size and function in 101 consecutive patients with Fontan palliation.
      Compared with studies in patients without implants, in whom 100% of anatomic
      segments were adequately visualized and the median image quality grade for
      ventricular function assessment was 5 of 5, the presence of any implant (54% of
      studies) reduced the proportion of adequately imaged anatomy to 77% (p <0.001)
      and the median image quality grade for ventricular function assessment to 3 of 5
      (p <0.001).

PMID- 15721125
TI  - Effect of cirrhosis and liver transplantation on the gender difference in QT
      interval.
AB  - The effect of gender on the QT interval in patients with cirrhosis before and
      after liver transplantation and the relation between the QT interval and changes
      in gender hormones after liver transplantation were assessed. The study showed
      that (1) physiologic gender difference in the QTc interval is abolished in
      cirrhosis, and it is not restored after liver transplantation, and (2) gender
      hormone concentrations had no effect on the QTc interval.

PMID- 15721126
TI  - Association of right ventricular dysfunction with in-hospital mortality in
      patients with acute pulmonary embolism and reduction in mortality in patients
      with right ventricular dysfunction by pulmonary embolectomy.
AB  - Twenty-one of 64 patients (33%) with pulmonary embolisms with right ventricular
      (RV) dilation and 6 of 126 patients (5%) with pulmonary embolisms without RV
      dilation died during hospitalization (p <0.001). In the 64 patients with RV
      dilation, in-hospital mortality occurred in 2 of 18 hemodynamically unstable
      patients (11%) who underwent pulmonary embolectomy, in 2 of 6 hemodynamically
      stable patients (33%) treated with thrombolytic therapy plus intravenous heparin,
      and in 17 of 40 hemodynamically stable patients (43%) treated with intravenous
      heparin (p <0.025 comparing pulmonary embolectomy with no pulmonary embolectomy).

PMID- 15721127
TI  - Utility of cardiopulmonary stress testing in assessing disease severity in
      children with pulmonary arterial hypertension.
AB  - This study sought to assess the safety of cardiopulmonary stress testing in 40
      children with pulmonary arterial hypertension and to compare exercise responses
      in this patient cohort with those of a healthy control population. Patients with
      pulmonary hypertension had significant impairment in aerobic capacity, with a
      peak oxygen consumption of 20.7 +/- 6.9 versus 35.5 +/- 7.4 ml/kg/min in healthy
      controls (p <0.0001). Peak oxygen consumption was strongly correlated with
      invasive measures of disease severity, including pulmonary vascular resistance
      index (r = -0.6, p = 0.006). Exercise testing can be performed safely in this
      group of patients and can yield valuable clinical information.

PMID- 15721128
TI  - Unusual clinical presentation in a family with catecholaminergic polymorphic
      ventricular tachycardia due to a G14876A ryanodine receptor gene mutation.
AB  - A family was identified, of whom which 11 members were carriers of the G14876A
      ryanodine 2 receptor mutation. All but 1 were symptomatic at the time of the
      study. Exercise testing showed bidirectional or polymorphic arrhythmias in 4
      patients, whereas in 5 patients, it showed monomorphic or rare minor polymorphic
      ventricular arrhythmias. Two young patients died suddenly at rest while asleep.
      This study demonstrates that arrhythmias occurring during exercise stress testing
      in patients affected by catecholaminergic polymorphic ventricular tachycardia
      (CPVT) could be minor even in very symptomatic patients. The diagnosis of CPVT
      must be considered in these patients with a familial history of typical CPVT.

PMID- 15721129
TI  - Severe regurgitation immediately after replacement of a dysfunctional
      bioprosthesis in the mitral valve position.
AB  - Severe regurgitation immediately after replacement of a cardiac valve with a
      mechanical prosthesis or a bioprosthesis is a rare occurrence. Such, however, was
      the case in the patient described.

PMID- 15721130
TI  - Another view of Dr. Perloff's personal coronary bypass experience.

PMID- 15721131
TI  - Postoperative care of the coronary artery bypass patient.

PMID- 15721132
TI  - Cardiac response to prolonged strenuous exercise: a physiologic model for
      stunning myocardium.

PMID- 15721134
TI  - Natriuretic peptides in sleep apnea.

PMID- 15721135
TI  - Activation of human dental pulp progenitor/stem cells in response to odontoblast
      injury.
AB  - In restorative dentistry, whilst moderate carious lesion treatment does not
      significantly compromise odontoblast cell survival, deep cavity preparation may
      lead to a partial death of these cells. However, newly formed odontoblast-like
      cells can replace the necrotic odontoblasts and secrete a reparative dentine
      matrix. Although several lines of evidence strongly suggest the presence of
      resting progenitor or stem cells in the dental pulp, little is known about the
      activation and migration of these cells in response to injury. Human immature
      third molars extracted for orthodontic reasons were used in this work to study
      the activation of progenitor/stem cells and their migration after deep cavity
      preparation involving in pulpal exposure using 5-bromo-2'-deoxyuridine labelling
      (BrdU). After incubation for 1 day, the BrdU was localised to the nuclei of cells
      in the perivascular area. The BrdU-immunolabelling exhibited a gradient. It was
      strong in the blood vessels surrounding the pulpal cavity and decreased in those
      away from the cavity. After incubation for 2 weeks, labelled cells were seen in
      the vicinity of the cavity. At 4 weeks, the immunolabelling was localised to the
      cavity area only. Control teeth without cavities or with shallow dentine cavities
      did not show any perivascular labelling after culture. These results clearly
      demonstrate that perivascular progenitor/stem cells can proliferate in response
      to odontoblast injury. They also show that these proliferating cells can migrate
      to the pulpal injury site in their tissue of origin simulating the situation in
      vivo.

PMID- 15721136
TI  - Role of injured endothelial cells in the recruitment of human pulp cells.
AB  - In restorative dentistry, deep cavity preparation may lead to partial destruction
      of the odontoblastic layer. However, newly formed odontoblast-like cells can
      replace the necrotic odontoblasts and secrete a reparative dentine matrix. While
      growth factors such as transforming growth factor beta1 (TGFbeta1) and bone
      morphogenetic proteins (BMP-2 and BMP-4) seem to be involved in the proliferation
      and differentiation of pulp cells, little is known about the migration of the
      newly proliferating stem cells to the injury site. Our hypothesis was that
      endothelial cell injury may be involved in directing these cells towards the
      injury site. For this study, human pulp fibroblasts and L929 cells were
      fluorescence-labeled by transduction with the Enhanced Green Fluorescent Protein
      (EGFP). Similarly, human umbilical vein endothelial cells (HUVEC) were labeled
      with the Discosoma Red Fluorescent Protein-2 (DsRed2). Cell migration was then
      studied in an insert cell culture system. The HUVEC cells were cultured in the
      lower compartment while the human pulp fibroblasts or L929 were in the upper
      compartment. After artificial injury to the HUVEC cells, only human pulp
      fibroblasts migrated to the lower compartment. At early time periods (4 days),
      migrating cells were randomly localized on the HUVEC layer. However, after 14 and
      20 days, they were perfectly aligned along the injury site. In the absence of
      injury, no migration was observed. These results suggest that, the endothelial
      injury is involved in the recruitment of odontoblast-like cells at the injury
      site.

PMID- 15721137
TI  - Osteoclast diseases and dental abnormalities.
AB  - Tooth eruption depends on the presence of osteoclasts to create an eruption
      pathway through the alveolar bone. In diseases where osteoclast formation, or
      function is reduced, such as the various types of osteopetrosis, tooth eruption
      is affected. Diseases in which osteoclast formation or activity is increased,
      such as familiar expansile osteolysis and Paget's disease, are associated with
      dental abnormalities such as root resorption and premature tooth loss. Less is
      known about the origin of the dental problems in these conditions as there are no
      rodent models of these diseases as yet. In this short review, the genes currently
      known to be mutated in human osteoclast diseases will be reviewed and, where
      known, the effect of osteoclast dysfunction on dental development described. It
      will focus on human conditions and only mention rodent disease where no clear
      data in the human are available.

PMID- 15721138
TI  - IGFs increase enamel formation by inducing expression of enamel mineralizing
      specific genes.
AB  - Insulin-like growth factors (IGF-I and IGF-II) have been shown to play an
      important role in growth and differentiation in a number of tissues including
      mineralizing bone. Little is known about their role in tooth mineralization.
      Previous work in our laboratory has shown the presence of IGFs ligands, their
      receptors, and their binding proteins during mouse tooth morphogenesis. The
      expression of IGF I coincides with the expression of amelogenin, ameloblastin and
      enamelin at the late bell and secretory stage. The objective of this study is to
      determine the mechanisms by which IGFs modulate enamel and dentin formation.
      Mouse first mandibular molars were dissected from E16 and E17 mouse embryos and
      placed in organ culture in the presence of IGF-I or IGF-II. The molars were
      harvested after 12 days for histological examination or 1 day for mRNA expression
      analysis by real-time RT-PCR. Our results show an increase in enamel deposition,
      and an induction of enamelin, amelogenin and collagen type I mRNA expression,
      while expression of DSPP was down-regulated. These results suggest that IGFs
      increase enamel formation by the induction of gene expression of enamel related
      genes. Studies are underway to determine a possible mechanism for these factors.

PMID- 15721139
TI  - Dental epithelial histo-morphogenesis in the mouse: positional information versus
      cell history.
AB  - Reciprocal epithelial-mesenchymal interactions control odontogenesis and the cap
      stage tooth germ mesenchyme specifies crown morphogenesis. The aim of this work
      was to determine whether this mesenchyme could also control epithelial
      histogenesis. Dental mesenchyme and enamel organ were dissociated from mouse
      first lower molars at E14. At this early cap stage, the enamel organ consists of
      four cell types forming the inner dental epithelium (IDE), primary enamel knot
      (PEK), outer dental epithelium (ODE) and the stellate reticulum (SR). Pelleted
      trypsin-dissociated single dental epithelial cells, which had lost all positional
      information, were reassociated to either dental mesenchyme or dissociated
      mesenchymal cells and cultured in vitro. Although with different timings, teeth
      developed in both types of experiments showing a characteristic dental epithelial
      histogenesis, cusp formation, and the differentiation of functional odontoblasts
      and ameloblasts. The rapid progression of the initial steps of histogenesis
      suggested that the cell history was not memorized. The dental mesenchyme, as well
      as dissociated mesenchymal cells, induced the formation of a PEK indicating that
      no specific organisation in the mesenchyme is required for this step. However,
      the proportion of well-formed multicusped teeth was much higher when intact
      mesenchyme was used instead of dissociated mesenchymal cells. The mesenchymal
      cell dissociation had consequences for the functionality of the newly-formed PEK.

PMID- 15721140
TI  - Role of the Notch signalling pathway in tooth morphogenesis.
AB  - Notch receptors are involved in cell fate decisions through the process of
      lateral inhibition or inductive signalling. Jagged2 belongs to the family of
      transmembrane proteins that serve as the ligands for Notch receptors. We have
      analysed the expression of the Jagged2 gene in developing mouse teeth. Jagged2
      expression is restricted in inner enamel epithelial cells that give rise to the
      ameloblasts. We have also examined the role of Jagged2 in tooth development using
      mutant mice that lack the domain of the Jagged2 protein required for interaction
      with the Notch receptors (DSL domain). Homozygous mutant mice die after birth,
      exhibit abnormal tooth morphology and fusions between the palatal and mandibular
      shelves. These results demonstrate that Notch signalling plays an essential role
      in tooth development.

PMID- 15721141
TI  - Studies on Pax9-Msx1 protein interactions.
AB  - Pax9 belongs to the Pax family of transcriptional regulators that are defined by
      a highly conserved DNA-binding region, the paired domain. Drosophila, mouse and
      human genetics have shown that Pax proteins play multiple roles in tissue
      patterning and organogenesis by mediating their functions in a highly tissue
      specific manner. Members of the Pax family, Pax9 and Pax1, act synergistically
      during vertebral formation. However, only Pax9 is essential for tooth formation.
      Furthermore, mutations of PAX9 are associated with human tooth agenesis. The
      highly tooth-specific molecular functions of Pax9 suggest that its activity is
      tightly regulated. Most likely, this occurs through interactions with other
      protein factors. Among the regulatory molecules that are expressed in dental
      mesenchyme, the Msx1 homeoprotein is of particular interest. The closely
      overlapping expression patterns of Pax9 and Msx1 are consistent with a role in
      epithelial-mesenchymal interactions. To demonstrate that Pax9 interacts with Msx1
      physiologically in vivo and in vitro, we performed co-immunoprecipitation and GST
      interaction assays. Our results indicate that there is a physical association
      between the two proteins. Our biochemical data, coupled with human genetic
      studies and expression analysis in a mouse model, indicate a functional
      relationship between Pax9 and Msx1 during tooth development.

PMID- 15721142
TI  - Expression of the Hedgehog antagonists Rab23 and Slimb/betaTrCP during mouse
      tooth development.
AB  - The sonic hedgehog signalling peptide has been demonstrated to play an important
      role in the growth and patterning of several organs including the tooth.
      Inappropriate activation of Shh signalling in the embryo causes various
      patterning defects and complex regulation of this pathway is important during
      normal development. A growing list of diverse antagonists have been identified
      that restrict Shh signalling in the embryo, however, only Ptc1, Gas1 and Hip1
      have been studied during tooth development. We have examined the expression
      pattern of the putative antagonists Rab23 and Slimb/betaTrCP during early murine
      odontogenesis and find that these molecules are expressed in the developing
      tooth. Interestingly, Rab23 demonstrates contrasting expression domains in the
      incisor and molar dentition during the cap stage, being restricted to the
      mesenchymal compartment of molar teeth and the epithelium of the enamel knot in
      incisor teeth. These findings provide the first evidence of distinct regulatory
      pathways for Shh in teeth of different classes.

PMID- 15721143
TI  - The eternal tooth germ is formed at the apical end of continuously growing teeth.
AB  - Rodent incisors are known to be continuously growing teeth that are maintained by
      both the cell-proliferation at the apical end and the attrition of the incisal
      edge. This type of tooth had a special epithelial structure for the maintenance
      of stem cells, showing the bulbous epithelial protrusion at the apical end. The
      morphological transition of the epithelial-mesenchymal compartment by serial
      transverse sections of the apical end toward the incisal direction is likely to
      reflect the development of the tooth germ in the prenatal stage. Based on the
      present histological and previous molecular biological studies, the special
      structure at the apical end is obviously different from the cervical loop giving
      rise to Hertwig's epithelial root sheath (HERS), in human, mouse and rat molar
      tooth germs. Hence, we propose a new concept that the eternal tooth bud producing
      various dental progeny is formed at the apical end of continuously growing teeth,
      and a new term "apical bud" for indicating this specialized epithelial structure.
      Furthermore, BrdU labelling analysis suggested that the guinea-pig molars, which
      were continuously growing teeth, also possessed plural specific proliferative
      regions and "apical bud" at the apical end.

PMID- 15721144
TI  - The Ectodysplasin and NFkappaB signalling pathways in odontogenesis.
AB  - Hypohidrotic ectodermal dysplasia (HED) is a congenital disorder affecting organs
      of ectodermal origin including teeth, hair and sweat glands. Defects in
      Ectodysplasin (tabby), Edar (downless) and Edar associated death domain (Edaradd)
      (crinkled) cause HED in both humans and mice. Ectodysplasin is a tumour necrosis
      factor (TNF) superfamily member whose downstream signalling is transduced by the
      inhibitor of kappaB kinase (IKK) complex and inhibitors of kappaB (IkappaB) to
      activate the transcription factor NFkappaB. NFkappaB signalling is involved in a
      wide range of cellular processes and at each stage the different family members
      must be tightly regulated for each function. Recent data have demonstrated the
      importance of this signalling pathway in odontogenesis, particularly in the
      formation of cusps. Here we review recent advances in our understanding of
      Ectodysplasin/NFkappaB signalling in tooth development and in particular the
      central role of the IKK complex.

PMID- 15721145
TI  - Apoptosis-related factors (Fas receptor, Fas ligand, FADD) in early tooth
      development of the field vole (Microtus agrestis).
AB  - Fas (CD95/APO-1) belongs to the TNF receptor (TNFR) family. Fas ligand binding
      followed by Fas-receptor oligomerisation leads to formation of a death-inducing
      signal complex starting with recruitment of the Fas-adapter protein (FADD).
      Components of this initiation complex (Fas, Fas-L, FADD) were correlated with
      apoptotic cells, detected by specific DNA fragmentation and morphological
      criteria. Apoptotic cells can be detected throughout the embryonic development of
      molar teeth. Restricted temporospatial distribution suggests several important
      roles for apoptosis in tooth morphogenesis. However, the mechanisms employed in
      dental apoptosis remain unclear. Frontal sections of the field vole at stage 13.5
      15.5 of embryonic development were exploited to investigate and correlate
      location of Fas, Fas-ligand, FADD molecules and apoptosis in developing first
      molars by immunohistochemistry. During these stages the primary enamel knot
      appears and is gradually terminated by apoptosis. Initially, apoptotic cells were
      demonstrated in the most superficial layer of the dental lamina. The number of
      TUNEL-positive cells expanded from late bud to cap stages. Restricted areas of
      apoptotic cells were found in the stalk and primary enamel knot. Fas, Fas-L and
      FADD were co-localised, particularly in the primary enamel knot, and the stalk,
      correlating with the occurrence of apoptosis in these areas. Fas-L, however, was
      also found in proliferating parts of the developing tooth germ, such as in the
      cervical loops. Interestingly, FADD molecules were also observed in areas, where
      Fas protein was not detected. According to the immunohistochemical data, Fas
      mediated signalling may have a triggering or enhancing role in dental apoptosis.
      This remains to be functionally confirmed.

PMID- 15721146
TI  - Immunohistochemical evidence for proteolipid protein and nestin expression in the
      late bell stage of developing rodent teeth.
AB  - In this study, the expression of proteolipid protein (PLP) and nestin is studied
      in the late bell stage of developing rodent teeth in neonatal rats. By using
      immunohistochemistry, it was shown that odontoblasts, ameloblasts and the stratum
      intermedium are positive for PLP in regions of active matrix deposition.
      Reactivity for nestin could be detected in the odontoblasts, stratum intermedium
      and in some of the apical processes of the ameloblasts. The fact that mutations
      in the PLP gene can cause disturbances in tooth form, number and eruption taken
      together with the presence of PLP reactivity in odontoblasts and ameloblasts of
      healthy animals, suggests a crucial role for PLP in developing teeth because of
      its structural supportive characteristics. These results also imply the possible
      use of PLP antibody as a new marker for, respectively, dentin and enamel
      secreting odontoblasts and ameloblasts. PLP and nestin expression could point to
      a possible similarity in function between the oligodendrocyte and the
      odontoblast, both derived from the neural crest. To compare with the situation in
      human tissue, PLP and nestin expression were preliminarily tested on human dental
      pulp. The odontoblasts were positive for both PLP and nestin.

PMID- 15721147
TI  - The expression pattern of hyaluronan synthase during human tooth development.
AB  - In previous studies, hyaluronan (HA) and its major cell surface receptor CD44
      have been suggested to play an important role during tooth development. HA
      synthases (HASs) are the enzymes that polymerize hyaluronan. Data on the
      expression pattern of HASs during tooth development is lacking and the aim of the
      present study was to investigate the localisation of HAS by immunohistochemistry
      in human tooth germs from different developmental stages. The distribution
      pattern of HAS in the various tissues of the "bell stage" tooth primordia
      corresponded to that of hyaluronan in most locations: positive HAS
      immunoreactivity was observed in the dental lamina cells, inner- and outer-enamel
      epithelium. On the stellate reticulum cells, moderate HAS signal was observed,
      similar to the layers of the oral epithelium, where faint HAS immunoreactivity
      was detected. At the early phase of dental hard tissues mineralization, strong
      HAS immunoreactivity was detected in the odontoblasts and their processes, as
      well as in the secretory ameloblasts and their apical processes and also, the
      pulpal mesenchymal cells. The HAS signals observed in odontoblasts and
      ameloblasts gradually decreased with age. Our results demonstrate that hyaluronan
      synthesised locally by different dental cells and these results provide
      additional indirect support to the suggestion that HA may contribute both to the
      regulation of tooth morphogenesis and dental hard tissue formation.

PMID- 15721148
TI  - Distribution and structure of dental enamel in incisors of Tabby mice.
AB  - OBJECTIVE: In Tabby mice, the Ta (EDA) gene is mutated. The resulting syndrome is
      homologous to hypohidrotic ectodermal dysplasia in humans. The Tabby phenotype is
      characterized by developmental defects of ectodermally derived structures. The
      teeth show aberrations in number, size and morphology. Dental enamel is a product
      of specialized epithelial cells, the ameloblasts. It was the aim of the present
      study to investigate the dental enamel phenotype in Tabby incisors, with emphasis
      on its distribution and structure. DESIGN: The incisors from five female Tabby
      and three female wild-type mice were sectioned and ground transversely, etched
      for 45s with 0.1% nitric acid, sputter-coated with gold-palladium, and observed
      in SEM. RESULTS: All measured dimensions were more variable in Tabby mice, as was
      the outline of the enamel-dentin junction. Maxillary incisors were wider in Tabby
      mice, while mandibular incisors were wider in wild-type mice. No significant
      difference in enamel thickness was observed. The enamel on the mesial aspect
      tended to extend further lingually in Tabby incisors in both jaws. On the lateral
      aspect, this tendency was only significant in mandibular incisors. The enamel
      dentin junction often lacked the mesial concavity. Instances of hypoplastic
      enamel were observed. The complex mouse enamel structure was generally well
      preserved in Tabby mice, only few instances of aberrant structure were observed.
      CONCLUSIONS: It is suggested that the reciprocal expression pattern of Ta and
      Edar (the Ta ligand receptor gene) in outer and inner enamel epithelium,
      respectively, may influence the position of the enamel-cementum junction.

PMID- 15721149
TI  - Changes in amelogenesis in the rat incisor following short-term hypocalcaemia.
AB  - There is a relationship between hypocalcaemia and the enamel hypoplasia. Earlier
      studies in rats have reported a severe hypocalcaemia and enamel hypoplasia a
      month after thyro-parathyroidectomy (TPTX). The aims of this study were to look
      at earlier stages and to attempt to correlate morphological changes with
      alterations in the distribution of amelogenin. Twenty-five Wistar rats were,
      under anaesthesia, thyro-parathyroidectomized. Sham operated rats were included
      as controls. After 14, 30 or 57 days, the animals were reanesthatized and the
      tissues fixed by intracardiac perfusion of fixative. The lower incisors were
      processed for light microscopy and immunogold electron microscopy. After 14 days
      the thyro-parathyroidectomised rats were severely hypocalcaemic but amelogenesis
      was morphologically similar to controls. After 30 and 57 days, enamel defects
      were observed in the late secretory and early maturation stages in the thyro
      parathyroidectomised rats. The immunocytochemical study revealed a concentration
      of stippled material immunolabelled for amelogenin at the secretory pole of the
      ameloblasts in the hypocalcaemic rats. The absence of enamel defects after 14
      days suggests that this was an insufficient hypocalcaemic period to induce
      morphological alterations. The concentration of stippled material containing
      amelogenin suggests that alterations in matrix formation may be the basis of the
      morphological changes.

PMID- 15721150
TI  - Explainable and critical periods during human dental morphogenesis and their
      control.
AB  - OBJECTIVE: To what extent is the current knowledge about regulatory and
      patterning processes gained from research on animal models (predominantly mouse)
      applicable to describe certain aspect of human prenatal dental development?
      METHODS: 3D-reconstructions were produced from serial sections of human dental
      primordia (Radlanski collection, Berlin) and scanning electron microscopic
      visualisation techniques were applied. RESULTS AND CONCLUSION: There are several
      examples, where present knowledge of regulatory processes allows the
      understanding of changes in outline and form. However, many other examples show
      that much more complex regulatory mechanisms should be expected to explain the
      details of human prenatal dental development.

PMID- 15721151
TI  - Amelogenin: lessons from evolution.
AB  - Amelogenin plays a crucial role in enamel structure and mineralization, but the
      function of its various domains is far to be understood. Evolutionary analysis
      seems to be a promising way to approach structure/function relationships. In this
      paper, we review the knowledge of amelogenin with a particular focus on what we
      have learnt from evolution, and we bring new data on the origin and evolution of
      this molecule. The comparison of amniote (reptiles and mammals) amelogenin
      sequences reveals that, in contrast to the well-conserved C- and N-terminal
      domains, the central region (most of exon 6) is highly variable. The evolutionary
      analysis indicates that it was created by repeated insertion of three amino acids
      (triplets ProXGlu or ProXX). In several mammalian lineages a new run of triplet
      insertions and deletions has occurred independently in a locus considered a hot
      spot of mutation for mammalian amelogenin. In lizard and snake amelogenin evolves
      rapidly. Sequence alignment reveals that several residues in the N- and C
      terminal regions were kept unchanged during 250 million years (MY), proving their
      importance for amelogenin structure and function. This alignment permits a rapid
      validation of the amelogenin mutations in human. Genome sequencing and gene
      mapping permitted to refine the amelogenin story, in relation to the common
      location (chromosome 4 in human) of several genes coding for dental proteins and
      SPARCL1, a SPARC (osteonectin) relative. Amelogenin shares a similar organisation
      with these genes and a blast search in databanks indicates a strong relationship
      between amelogenin, ameloblastin and enamelin. Taken together these data suggest
      that amelogenin could have originated from either ameloblastin or enamelin,
      themselves being created from SPARCL1, which itself originated from a SPARC
      duplication, 600 millions years ago.

PMID- 15721152
TI  - Are breeding teeth in Atlantic salmon a component of the drastic alterations of
      the oral facial skeleton?
AB  - Upriver spawning migration of starving Atlantic salmon (Salmo salar) involves
      drastic skeletal alterations, among which a toothless stage followed by the
      appearance of a new set of so-called breeding teeth has been described. To
      investigate this phenomenon, we examined the patterns of tooth replacement on the
      lower jaws in different life stages of wild animals before and after spawning.
      Prior to spawning, every position held either a functional or a replacement
      tooth, both in first-time (grilse) and repetitive (salmon) spawners. Teeth were
      in a similar developmental stage every three positions along the tooth row. A
      functional tooth occurred in every third position and intermediate positions were
      taken by developing teeth. Within the process of replacement, teeth were resorbed
      and not shed. Our observations on an uninterrupted tooth replacement pattern
      provided no evidence of an intermediate toothless stage nor of a specialized
      breeding-teeth generation. Only animals that survived spawning (kelts) showed a
      highly variable tooth pattern, but with the initial "every third position"
      pattern still recognizable in some animals. We hypothesise that previous accounts
      describing a complete tooth loss/replacement relate to proliferation of the oral
      mucosa that conceals the teeth prior to the breeding period and to the use of
      maceration techniques that could have removed all teeth with an incompletely
      mineralised base.

PMID- 15721153
TI  - The supernumerary cheek tooth in tabby/EDA mice-a reminiscence of the premolar in
      mouse ancestors.
AB  - OBJECTIVE: A supernumerary cheek tooth occurs mesially to the first molar in
      tabby/EDA (Ta) mice affected by hypohidrotic ectodermal dysplasia. The
      supernumerary tooth (S) has been hypothetically homologized to the premolar,
      which has disappeared during mouse evolution. DESIGN: This hypothesis was tested
      using available morphological data on the lower cheek teeth in wild type (WT) and
      Ta mice. RESULTS: The presence of S is accompanied by a reduction in the mesial
      portion of the M(1) in mutant mice. 3D reconstructions suggest that the S in Ta
      homo/hemizygous embryos originates from a split off the mesial portion of the
      first molar (M(1)) cap. In WT embryos, two vestigial tooth primordia are
      transiently distinct in front of the M(1). The distal vestige has the form of a
      wide bud and participates during the development of the mesial portion of the
      M(1). This bud has been homologized with the vestigial primordium of the fourth
      premolar of mouse ancestors. The premolar disappearance coincided with a mesial
      lengthening of the M(1) during mouse evolution. The incorporation of the distal
      premolar vestige into the mesial part of the M(1) in WT embryos can be regarded
      as a repetition of the premolar disappearance during evolution. CONCLUSION: :
      Ontogenetic and phylogenetic data support that the S in Ta mice arises due to the
      segregation of the distal premolar vestige from the molar dentition and thus
      represents an evolutionary throwback (atavism).

PMID- 15721154
TI  - Altered gene expression in human cleidocranial dysplasia dental pulp cells.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant disorder characterised by
      defects of bone and tooth development. The dental manifestations in CCD patients
      include supernumerary teeth, delayed tooth eruption, tooth hypoplasia and absence
      of cellular cementum formation. This disorder is associated with mutations in the
      osteoblast-specific transcription factor Runx2. To identify morphological and
      molecular alterations associated with CCD dental tissues, human primary dental
      pulp cell cultures were established from age- and sex-matched CCD and normal
      patients. Dental pulp cells were compared for general morphology, proliferation
      rates, and gene expression profiles using cDNA microarray technology. CCD pulp
      cells were about four-fold larger than normal cells, however the normal pulp
      proliferation rates were two- and three-fold greater at time points tested than
      the CCD cells. Of the 226 genes analysed by blot microarray, 18.6% displayed
      significant differences at least two-fold in expression levels. This includes 25
      genes (11.1%) that were up-regulated, while 17 (7.5%) that were down-regulated in
      the CCD cells as compared to the normal cells. Expression of selected genes was
      further verified by quantitative real-time polymerase chain reaction (qRT-PCR).
      Comparison between the CDD and normal cells revealed that gene expression of
      cytokines and growth factors, such as leukemia inhibitory factor (LIF),
      interleukin-6 (IL-6) and transforming growth factor beta receptor II (TGF
      betaRII) and vascular endothelial growth factor B (VEGFB) were higher while bone
      morphogenetic protein 2 (BMP2) was lower in the CCD cells. Furthermore, potential
      Runx2 binding sites were found in all putative target gene promoters. This study
      suggests that in addition to bone and tooth cell differentiation, Runx2 may be
      involved in controlling cell growth during tooth development.

PMID- 15721155
TI  - Case report of a rare syndrome associating amelogenesis imperfecta and
      nephrocalcinosis in a consanguineous family.
AB  - A rare syndrome associating amelogenesis imperfecta (AI) with nephrocalcinosis
      has been reported. The purpose of this study is to characterise the phenotype of
      a consanguineous family presenting amelogenesis imperfecta, delayed permanent
      teeth eruption and nephrocalcinosis. Six family members were examined. Ground
      sections of the case index deciduous teeth and biopsies of enlarged dental
      follicles were analysed. The patients's parents were first cousins. The case
      index had yellow discoloration and altered teeth shapes, retention of deciduous
      teeth, and delayed eruption. Panoramic radiographs revealed multiple enlarged
      pericoronal follicles in unerupted teeth and generalised intrapulpal
      calcifications. Renal ultrasound showed the presence of nephrocalcinosis. No
      other family members presented enamel defects or nephrocalcinosis.
      Histologically, the enamel appeared hypoplastic, and dental follicles indicated
      pericoronal hamartoma. The consanguineous marriage suggests an autosomal
      recessive mode of inheritance. Further studies are necessary to clarify the
      genetic defect behind this syndrome that associates AI, nephrocalcinosis and
      impaired tooth eruption.

PMID- 15721156
TI  - Tooth size in patients with supernumerary teeth and a control group measured by
      image analysis system.
AB  - OBJECTIVE: The aim of this study was to compare tooth size measurements between
      patients with supernumerary teeth and a control group. METHOD: The supernumerary
      group consisted of 56 subjects (21 females and 35 males) and the control group of
      40 subjects (20 females and 20 males). All available permanent teeth on the
      dental casts were imaged and measured from both buccal and occlusal views using
      an image analysis system. Mesio-distal, bucco-lingual or occluso-gingival
      dimensions, area and perimeter were measured from each view. RESULTS:
      Supernumerary tooth patients tended to have larger tooth size measurements for
      almost all variables than controls. Significant differences (p<0.05) were found
      for the mesio-distal dimension of the upper and lower incisors and the bucco
      lingual dimensions of the lower first premolars. CONCLUSIONS: The results are
      compatible with supernumerary teeth being a complex dental anomaly with a
      multifactorial aetiology in which both genetic and environmental factors are
      important. There is some evidence of a local effect with greater differences in
      tooth dimension adjacent to the site of the supernumeraries.

PMID- 15721157
TI  - Fluctuating dental asymmetry of multiple crown variables measured by an image
      analysis system.
AB  - OBJECTIVE: Fluctuating dental asymmetry as an indication of the effect of
      environmental insults during tooth development requires further investigation.
      The aim of this study was to assess asymmetry in tooth crown dimension for the
      increased range of parameters possible with image analysis compared to previous
      manual measurements. METHODS: Study models of 25 male and 25 female white
      Caucasian subjects were measured from buccal and occlusal views to determine
      mesio-distal, bucco-lingual, occluso-gingival and tooth surface area dimensions
      using image analysis. Method errors were assessed by the repeatability
      coefficient RC and asymmetry assessed calculating intra-class correlation
      coefficients between pairs of antimere teeth. RESULTS: The method errors
      calculated using RC were small. There was a high degree of symmetry with
      correlation coefficients with a range of 0.67-0.96 for linear measurements and
      0.80-0.97 for tooth surface areas. No significant differences were found between
      the genders or between the upper and lower jaws. Asymmetry tended to follow a
      pattern in morphogenic tooth fields with the mesial tooth showing greater
      symmetry than the more distal. There were differences in the degree of symmetry
      among the variables measured with the mesio-distal dimension showing the greatest
      symmetry. CONCLUSIONS: This new technique was reliable and readily applicable,
      providing also a greater range of measurements. While the asymmetry generally
      followed a similar pattern to earlier manual studies, there were variations in
      the degree of symmetry between different parameters.

PMID- 15721158
TI  - Tissue engineering of teeth using adult stem cells.
AB  - Tooth development, a process which occurs in the developing embryo, involves the
      reciprocal and sequential signalling between epithelial and mesenchymal tissue of
      the developing first branchial arch. The oral epithelium produces the first
      inductive signals for odontogenesis at around E10.0, which trigger off a cascade
      of events that result in the formation of a tooth. We have engineered a tooth in
      vitro by harnessing the basic principles of odontogenesis and the inductive
      capability of the oral epithelium of the developing embryo. We replaced the
      mesenchymal portion of the developing mandibular primordium with aggregates of
      stem cells from embryos as well as stem cells taken from adult mice. The cell
      aggregates were covered with embryonic epithelium from E10.0 mouse embryos to
      form recombinant explants. In vitro culture of these recombinant explants
      resulted in the induction of early tooth marker genes in the cell aggregates,
      indicating that the cells were able to respond to the odontogenic signals
      produced by the oral epithelium. In vivo culture of explants resulted in the
      induction of Dspp within the cell aggregates indicating that tooth tissue was
      present. Three recombinant explants, where the cell aggregates consisted of adult
      bone marrow cells, produced teeth. To determine whether the oral cavity would be
      able to sustain the growth of an implanted tooth germ, E14.5 molar rudiments were
      implanted into the diastema region of the maxilla of adult mice. The resulting
      teeth appeared to be normal in size and were connected to the underlying bone.
      These experiments are an indication that it is possible to induce odontogenesis
      and engineer a tooth using adult cells of non-dental origin. They also indicate
      that developing tooth germs could be successfully implanted into the gingiva of
      patients.

PMID- 15721159
TI  - Developmental analysis and computer modelling of bioengineered teeth.
AB  - Here we present the developmental progression of bioengineered pig teeth from 1
      to 25 weeks of development. We demonstrate that 2-25 week implants contained
      embryonic tooth bud- and cap-stage tooth structures consisting of dental
      epithelium expressing the sonic hedgehog gene and condensed dental mesenchyme.
      Implants harvested at 18-25 weeks also contained tooth bud-like structures, as
      well as mature tooth structures containing enamel, dentin and pulp tissues.
      Immunohistochemical analyses confirmed the expression of dentin- and enamel
      specific proteins in differentiated bioengineered tooth tissues. Three
      dimensional computer modelling further demonstrated a spatial organization of
      enamel, dentin and pulp tissues resembling that of natural teeth. We conclude
      that bioengineered teeth commonly exhibit morphological stages characteristic of
      naturally forming teeth. Furthermore, the presence of immature tooth buds at all
      times assayed and increased numbers of bioengineered tooth structures over time
      suggests that porcine dental progenitor cells maintain the ability to form teeth
      for at least 25 weeks.

PMID- 15721160
TI  - Surface chemistry of enamel apatite during maturation in relation to pH:
      implications for protein removal and crystal growth.
AB  - Apatite crystal growth rate and morphology in mineralized tissues are considered
      to be controlled by surface interaction with extracellular matrix proteins.
      During enamel maturation where protein is finally removed from crystal surfaces
      to permit massive crystal growth, pH oscillates between approximately 5.8 and
      approximately 7.2. With this in mind, a study of enamel apatite surface chemistry
      in terms of local environmental pH was undertaken. Using atomic force microscopy
      adhesion force measurements were made between hydroxylated or carboxylated
      cantilever tips and maturation stage crystals between pH 2 and 10. Adhesion force
      increased from pH 10 to a maximum at pH 6.6 presumably due to increased hydrogen
      bonding due to replacement of surface cations (Na, Ca, Mg) with protons and/or
      protonation of phosphate per se. Below pH 6.6 adhesion force decreased and became
      very variable indicating that the surface had become unstable probably due to
      removal of fully protonated phosphate from the surface by adherence to the
      cantilever tip. Frictional force measurements also revealed 2-3, approximately 30
      nm diameter high friction domains in bands across the crystal long axis. Their
      location mirrored the binding pattern of similarly sized amelogenin aggregates
      seen in vitro. The data suggests that specific protein binding sites may exist on
      crystal surfaces and may be released at lower pH by protonation which would lower
      cationic charge on both crystal surface and ionic charge on the protein.
      Instability of the crystal surface could also play a role.

PMID- 15721161
TI  - New cellular models for tracking the odontoblast phenotype.
AB  - Odontoblasts and osteoblasts differ functionally and histologically. Because of
      their close relationship, mesenchymal cells derived from teeth and bone are
      difficult to distinguish ex vivo. Indeed, the main non-collagenous components of
      the odontoblastic extracellular matrix, dentin sialoprotein (DSP) or dentin
      matrix protein 1 (DMP1), have also been detected in osteoblasts. The need to
      develop cellular models of odontoblast differentiation and to identify markers
      specific for the odontoblast lineage, has led us to establish clonal cell lines
      from tooth germs of day 18 mouse embryos transgenic for an adenovirus-SV40
      recombinant plasmid. In this study, we analyzed the phenotypes of three
      independent clones by RT-PCR and Western blot. These clones synthesised DSP, DMP1
      and other extracellular matrix proteins typical of the odontoblast and are
      therefore likely to be derived from the pulp. Transcripts encoding a set of
      homeobox proteins involved in craniofacial development, such as Pax9, Msx1,
      Cbfa1, Dlx2 and 5 were also expressed albeit at a different level. These features
      of the pulpal clones are shared by the C1 mesodermal cells that are capable of
      differentiating along osteogenic, chondrogenic or adipogenic lineages In
      contrast, transcripts for two LIM-domain homeobox family genes (Lhx6 and Lhx7)
      were only detected in the dental clones. Since these genes are preferentially
      expressed in the mesenchyme of the developing tooth, this suggests that our
      transgenic-derived cell lines retain intrinsic properties of odontoblastic cells.
      They may help to characterise genes specifying the odontoblast phenotype and the
      signalling pathways underlying odontoblast differentiation.

PMID- 15721162
TI  - Is the lingual forming part of the incisor a structural entity? Evidences from
      the fragilitas ossium (fro/fro) mouse mutation and the TGFbeta1 overexpressing
      transgenic strain.
AB  - Our objective was to study the teeth of a mutant mice fro/fro that display severe
      forms of osteogenesis imperfecta. One day and 8 week-old fro/fro and +/fro
      heterozygote mice (wild type, WT) were processed for light and scanning electron
      microscopy. The genetic defect, shown to be located on chromosome 8, induced
      alveolar bone and teeth hypomineralisation. Due to defective cell proliferation
      in the fro/fro, the distal growth of the mandibular incisors was impaired.
      Immunolabelling revealed an increase of chondroitin/dermatan sulphate, whereas no
      difference was detected in dental tissues for decorin and biglycan. Amelogenin
      expression was decreased in the incisor and enhanced in the molar. Dentin
      sialoprotein was below the level of detection in the fro/fro, whereas osteonectin
      and osteopontin were unchanged. The main target of the mutation was seen in the
      lingual part of the incisor near the apex where dentine formation was delayed. In
      the molars, bulbous roots with obliteration of the pulp chamber were seen. In the
      TGFbeta1 overexpressing mice, the lingual root-analogue part of the incisor was
      missing. In the molar, short roots, circumpulpal dentine of the osteodentine type
      and pulp obliteration were seen. It may be noted that, although the mutant and
      transgenic strains mutations are two different genetic alterations not related to
      the same defective gene, in both cases the expression of the dentin sialoprotein
      is altered. Altogether, the present data suggest that the lingual forming part of
      the incisor seems to be an anatomical entity bearing its own biological
      specificities.

PMID- 15721163
TI  - The patterning of hypodontia in a group of young adults in Sheffield, UK.
AB  - OBJECTIVE: Identifying the patterning of congenitally absent teeth will
      contribute to understanding the aetiology of hypodontia. The aim of this study
      was to investigate patterns of hypodontia in a group of young adults in
      Sheffield, UK involving specific tooth types, gender differences and
      maxilla:mandible and left:right correlations. METHODS: The patients were 198
      unrelated Caucasian young adults (86 males and 112 females) with non-syndromic
      hypodontia. Statistical methods included the multivariate techniques of cluster
      analysis and principal components analysis and associated display devices of
      circular dotplots and biplots. Autologistic regression was used to model the
      relationship of the presence or absence of a particular tooth to the status of
      other teeth. RESULTS: The results revealed distinct patterns of dependence.
      Common patterns included either third molars and second premolars missing in all
      quadrants and/or combinations of these two tooth types and the incisors. The
      gender of the patient and the severity of hypodontia did not have a significant
      effect on patterns of tooth type absence. If a tooth was missing, the odds ratios
      that the same tooth type in the horizontally or vertically opposite quadrant was
      also missing were some 20 times higher than if the tooth was present. For
      diagonally opposite quadrants the dependence was much weaker. CONCLUSIONS: These
      statistical techniques are valuable for increasing understanding of hypodontia
      and identifying groups of patients for genetic studies.

PMID- 15721165
TI  - Activation of protein kinase C reduces benzodiazepine potency at GABAA receptors
      in NT2-N neurons.
AB  - Phosphorylation of GABA(A) receptors (GABARs) by protein kinase C (PKC) modulates
      GABAR function and allosteric enhancement by benzodiazepines and barbiturates.
      However, the effects of phosphorylation have been inconsistent, possibly due to
      variability in neuron or GABAR populations. We used NT2-N neurons to address this
      issue in a more homogeneous cell population. Whole-cell and gramicidin
      "perforated-patch" recordings were used to analyze changes in GABAR currents
      induced by preincubation with 4beta-phorbol-12,13-dibutyrate (PDBu), the inactive
      4alpha-phorbol-didecanoate (4alpha-PDD) or bisindolylmaleimide (BIM, a PKC
      inhibitor). PDBu, but not 4alpha-PDD, caused a rightward shift of the
      concentration-response curve (C/R) for diazepam enhancement, without affecting
      maximal enhancement. BIM blocked the rightward shift of the diazepam C/R induced
      by PDBu. PDBu did not alter the GABA C/R or the current reversal potential. The
      PKC effect was specific to the benzodiazepine site, as PDBu did not alter
      potentiation of GABAR currents by pentobarbital. Exposure to diazepam (10 microM)
      for 7 days reduced maximal diazepam enhancement without affecting the EC(50);
      PDBu also caused a small rightward shift of the diazepam EC(50) in these cells.
      PKC activation reduced the apparent affinity of diazepam at NT2-N GABARs without
      altering maximal enhancement, suggesting decreased allosteric coupling of the
      benzodiazepine and GABA sites.

PMID- 15721164
TI  - mGlu and NMDA receptor contributions to capsaicin-induced thermal and mechanical
      hypersensitivity.
AB  - Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors, some of
      which are localized in the spinal cord dorsal horn, and are involved with pain
      perception. The anti-nociceptive effects of intrathecal (i.t.) pretreatment with
      various mGlu receptor agonists and antagonists were assessed in Long Evans rats
      with mechanical and thermal hypersensitivity after sub-dermal injection of
      capsaicin in the hindpaw. Selective group II (aminopyrrolidine-2R,4R
      dicarboxylate, APDC) and group III (l-2-amino-4-phosphonobutyrate, L-AP4)
      agonists, as well as selective mGlu(1) (1-aminoindan-1,5(R,S)-dicarboxylic acid,
      AIDA) and mGlu(5) (2-methyl-6-(phenylethynyl)-pyridine, MPEP) receptor subtype
      antagonists were compared with that of an NMDA receptor antagonist (dizocilipine
      maleate, MK-801). The rats were observed for signs of capsaicin-induced
      mechanical and thermal hypersensitivity 15 min after capsaicin injection, and 20
      min following i.t. drug administration. Results indicate there was a dose
      dependent reduction in capsaicin-induced mechanical hypersensitivity for all mGlu
      receptor agents; with maximal increases in mechanical thresholds that were 7-fold
      for AIDA and APDC, 7.5-fold for L-AP4 and 5.6-fold for MPEP. However, only a weak
      reduction (often non-significant) in thermal hypersensitivity was observed with
      each of the mGlu receptor drugs; thermal latencies were maximally increased by
      125% (AIDA), 0% (MPEP), 8% APDC and 205% (L-AP4). By contrast, the highest dose
      of MK-801 was able to significantly reduce both mechanical (maximal 6.67-fold
      increase in threshold) and thermal (maximal 3-fold increase in latencies)
      hyperalgesia. We conclude that mGlu receptors contribute to the development of
      mechanical allodynia, but not thermal hyperalgesia, following capsaicin injury;
      while iGluRs may contribute to both thermal and mechanical hypersensitivity.

PMID- 15721166
TI  - Mechanisms of allosteric modulation at GABAB receptors by CGP7930 and GS39783:
      effects on affinities and efficacies of orthosteric ligands with distinct
      intrinsic properties.
AB  - We determined the effects of the allosteric gamma-aminobutyric acid B receptor
      modulators CGP7930 and GS39783 on binding and function of orthosteric ligands
      with distinct intrinsic properties. In radioligand binding (saturation or
      displacement) experiments, the affinities of a number of competitive antagonists
      were decreased by the modulators, with no change in receptor number. The binding
      curves of the partial agonist CGP47656 comprised a high and a low affinity
      component; the affinity of the former was increased by the allosteric agents. The
      maximal stimulation of GTP[gamma](35)S binding via recombinant GABA(B) receptors
      by CGP47656 was increased 4-fold in the presence of 30 microM CGP7930 or GS39783.
      Two compounds known so far as "silent" competitive GABA(B) receptor antagonists,
      CGP35348 and 2-OH-saclofen, did not stimulate GTP[gamma](35)S binding on their
      own, but became low efficacy partial agonists in the presence of the two
      modulators. The potency of GABA to inhibit the formation of cAMP induced by a
      forskolin analog in a recombinant CHO cell line expressing GABA(B) receptors was
      increased by the modulators. CGP35348 and 2-OH-saclofen, like CGP47656, were
      partial agonists on their own in this assay, and the allosteric modulators
      increased the potency as well as the efficacy of all three compounds. With
      CGP52432, there was a trend towards inverse agonism in the cAMP assay. These
      results show that the intrinsic properties of orthosteric ligands are highly
      dependent on the characteristics of the assay system used and that allosteric
      modulators are useful tools for elucidating these properties.

PMID- 15721167
TI  - The effect of competitive antagonist chain length on NMDA receptor subunit
      selectivity.
AB  - The widely-used N-methyl-D-aspartate (NMDA) receptor antagonists (R)-4-(3
      phosphonopropyl) piperazine-2-carboxylic acid ((R)-CPP) and (R)-2-amino-7
      phosphonoheptanoate ((R)-AP7) are frequently used as general NMDA receptor
      antagonists and assumed not to display significant selectivity among NMDA
      receptor NR2 subunits. However, electrophysiological studies have suggested that
      certain longer chain N-methyl-D-aspartate (NMDA) receptor competitive
      antagonists, such as (R)-CPP are ineffective at subpopulations of NMDA receptors
      in the red nucleus, superior colliculus, and hippocampus. Using recombinant
      receptors expressed in Xenopus oocytes, we have examined the effect of antagonist
      chain length on NR2 subunit selectivity. All antagonists displayed the potency
      order (high to low affinity) of NR2A > NR2B > NR2C > NR2D, however the longer
      chain antagonists (having 7 instead of 5 bond lengths between acidic groups)
      displayed much greater subunit selectivity than their short-chain homologues. For
      example (R)-CPP displayed a 50-fold difference in affinity between NR2A
      containing and NR2D-containing NMDA receptors, while the shorter chain homologue
      4-(phosphonomethyl) piperazine-2-carboxylic acid (PMPA) displayed only a 5-fold
      variation in affinity. These results can account for the earlier physiological
      findings and suggest that longer chain antagonists such as (R)-CPP and (R)-AP7
      should not be used as general NMDA receptor antagonists.

PMID- 15721168
TI  - Peripherally acting NMDA receptor/glycineB site receptor antagonists inhibit
      morphine tolerance.
AB  - The present study focused on the role of peripheral ionotropic N-methyl-D
      aspartate (NMDA) receptors in the development of tolerance to morphine-induced
      antinociception. An initial experiment revealed that NMDA channel blocker
      memantine, and NMDA receptor/glycine(B) site antagonist MRZ 2/576 inhibited
      maximal electroshock-induced convulsions (MES) in female NMR mice with respective
      potency of 5.93 and 20.8 mg/kg, while other NMDA receptor/glycine(B) site
      antagonists MRZ 2/596 and MDL 105,519 were ineffective, supporting lack of CNS
      activity of the latter two agents. This observation was also supported by blood
      brain barrier experiments in vitro. In male Swiss mice, morphine (10 mg/kg) given
      for 6 days twice a day (b.i.d.) produced tolerance to its antinociceptive effects
      in the tail-flick test. The NMDA receptor/glycine(B) site antagonists, MRZ 2/576
      at 0.03, 0.1, 0.3 mg/kg and MRZ 2/596 at 0.1, 0.3, 3 and 10 mg/kg attenuated the
      development of morphine tolerance. Similarly, in male C57/Bl mice, morphine (10
      mg/kg) given for 6 days b.i.d. produced tolerance to its antinociceptive effects
      in the tail-flick test. Like in Swiss mice, in C57/Bl mice morphine tolerance was
      attenuated by both MRZ 2/576 and MRZ 2/596. Another NMDA receptor/glycine(B) site
      receptor antagonist, MDL 105,519 (that very weakly penetrates to the central
      nervous system) also inhibited morphine tolerance at the dose of 1 but not 0.1
      mg/kg. Moreover, both naloxone hydrochloride (5 and 50 mg/kg) and centrally
      inactive naloxone methiodide (50mg/kg) inhibited morphine tolerance suggesting
      the involvement of peripheral opioid receptors in this phenomenon. The present
      data suggest that blockade of NMDA receptor/glycine(B) sites in the periphery may
      attenuate tolerance to the antinociceptive effects of morphine.

PMID- 15721169
TI  - Munc18-dependent regulation of synaptic vesicle exocytosis by syntaxin-1A in
      hippocampal neurons.
AB  - The fusion of secretory vesicles with the plasma membrane requires the formation
      of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
      complexes between the vesicle-SNARE vesicle-associated membrane protein present
      on the vesicular membrane and the target-SNAREs SNAP-25 and syntaxin-1A. Syntaxin
      1A fluctuates between an open and closed form allowing it to selectively bind to
      different biological effectors in different conformations. In the open form, it
      can participate in SNARE complex formation, however, in the closed form it
      negatively regulates N- and P/Q-type voltage-dependent calcium channels, and is
      capable of inhibiting calcium influx. Thus paradoxically, syntaxin appears to
      have both positive and negative roles in controlling calcium-driven synaptic
      vesicle fusion at synaptic terminals. We show here that overexpression of
      syntaxin-1A inhibited exocytosis, in a manner that could be rescued by either
      elevating or reducing external calcium, or increasing action potential firing
      frequency. Elevating the level of Munc18 by coexpression with syntaxin-1A also
      abolished this inhibition, suggesting that Munc18 serves to limit the negative
      regulatory role of syntaxin by binding to, and thereby buffering, its closed
      form. Our results also indicate that syntaxin can control the frequency-response
      characteristics of the presynaptic fusion machinery.

PMID- 15721170
TI  - Serotonergic modulation of carbachol-induced rhythmic activity in hippocampal
      slices.
AB  - Fast rhythmic activity in a frequency range between 20 and 40 Hz occurs in vitro
      in hippocampal area CA3 after activation of muscarinic receptors. Here we show
      that carbachol-induced rhythmic activity is modulated by serotonin (5-HT).
      Spectral analysis reveals that 5-HT (0.3-30 microM) decreases power, but not
      frequency, of rhythmic activity in a concentration-dependent and reversible
      manner. The 5-HT(1A) agonists 8-OH-DPAT and buspirone mimic the effect of 5-HT,
      whereas the selective 5-HT(1A) receptor antagonist WAY-100635 (1 microM)
      significantly prevents the effect of 5-HT. In contrast to the effect of 5-HT(1A)
      agonists, the 5-HT(2) agonist DOI increases spectral power and prevents the
      reduction of spectral power by 5-HT. Application of WAY-100635 alone has no
      effect on rhythmic activity. Likewise, the 5-HT(2) antagonist ritanserin (10
      microM) does not affect rhythmic activity, or its reduction by 5-HT. Finally, the
      5-HT re-uptake inhibitor fluoxetine significantly decreases rhythmic activity in
      the presence of a low concentration of 5-HT, suggesting that 5-HT released from
      terminals in the slice likely reduces rhythmic activity. These results strongly
      implicate 5-HT(1A) and 5-HT(2) receptors in the modulation of spectral power of
      carbachol-induced rhythmic activity and that 5-HT(1A) receptors are responsible
      for the prevailing effect of 5-HT.

PMID- 15721171
TI  - The immunophilin ligand FK506 protects against methamphetamine-induced
      dopaminergic neurotoxicity in mouse striatum.
AB  - Repeated use of methamphetamine (MAP) is known to cause neurotoxicity in the
      dopaminergic neurons of the striatum. Recently, we reported that FK506, a
      calcineurin inhibitor and immunosuppressive agent, could attenuate acute
      behavioral changes and the development of sensitization after administration of
      MAP. In this study, we investigated the effects of FK506 on the neurotoxicity in
      the dopaminergic neurons induced by repeated administration of MAP. BALB/c mice
      were injected subcutaneously (s.c.) with vehicle (10 ml/kg) or MAP (4 mg/kg) four
      times every 2h. Vehicle (10 ml/kg) or FK506 (0.1, 0.3, 1 or 3 mg/kg i.p.) was
      administered 15 min before the first MAP administration. Three days later, we
      assessed the contents of dopamine (DA) and its major metabolite, 3,4
      dihydroxyphenylacetic acid (DOPAC), in the mouse striatum using high-performance
      liquid chromatography (HPLC). We also examined the immunohistochemistry of
      dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the mouse brain.
      Repeated administration of MAP decreased significantly the contents of DA and
      DOPAC in the mouse striatum, and pretreatment with FK506 inhibited significantly
      the reduction of DA and DOPAC in the mouse brain by repeated administration of
      MAP. Furthermore, repeated administration of MAP decreased significantly the
      immunoreactivity of DAT and TH in the striatum as compared to controls.
      Pretreatment with FK506 (3 mg/kg) attenuated significantly the reduction of DAT
      and TH immunoreactivity after repeated administration of MAP. These results
      suggest that FK506 shows protective effects on the MAP-induced neurotoxicity in
      the dopaminergic neurons of the mouse striatum.

PMID- 15721172
TI  - Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa.
AB  - The mechanisms underlying levodopa-induced dyskinesias are unclear. They might
      involve impairment of the buffering capacity for dopamine, resulting from loss of
      nigral dopaminergic cells and the subsequent degeneration of their terminals in
      striatum. This study investigated the role of striatal buffering in the
      development of dyskinesias. We used nomifensine, a selective dopamine reuptake
      blocker, to pharmacologically impair presynaptic buffering capacity in normal
      squirrel monkeys. Dyskinesias were assessed at 30-min intervals for 4 h after
      twice-daily treatment with drug. As previously reported by our group, animals
      receiving levodopa alone (15 mg/kg) exhibited dyskinetic behavior. Treatment with
      nomifensine alone (3 mg/kg) also induced dyskinesias. Furthermore, combining
      levodopa with nomifensine significantly increased dyskinesias. Over 4 weeks of
      treatment, the animals developed tolerance to the dyskinesia-inducing effect of
      nomifensine. The development of tolerance was prevented by concurrent treatment
      with levodopa. These results show that impairing buffering by preventing dopamine
      reuptake can induce dyskinesias and can also augment levodopa-induced
      dyskinesias. Thus, this study suggests that diminished buffering capacity for
      dopamine could play a role in the development of dyskinesias, and that an
      endogenous mechanism might exist that ameliorates dyskinesias.

PMID- 15721173
TI  - Characterization of the neuroprotective activity of rasagiline in cerebellar
      granule cells.
AB  - Rasagiline (N-propargyl-1-R-aminoindan) is a new selective inhibitor of MAO-B
      which is in development for the treatment of Parkinson's disease. The aim of the
      present study was to evaluate the neuroprotective properties of rasagiline and
      characterize the mechanism by which it exerts its neuroprotective effect in
      cerebellar granule cells. Cerebellar granule cells were prepared from 7 to 8 days
      postnatal Sprague-Dawley rats and maintained in high K(+) (25 mM) medium.
      Rasagiline increased the survival of cerebellar granule cells treated with
      cytosine beta-D-arabinofuranoside (Ara-C), L-buthionine-(S,R)-sulfoximine (BSO)
      or glutamate (100 microM) but did not reduce cell death induced by transferring
      the cells to physiological K(+) concentration (5 mM) or by serum deprivation.
      Examination of different derivatives of rasagiline showed that the propargyl
      moiety is essential to the neuroprotective effect of these molecules, as the
      compound 1-R-aminoindan (a major metabolite of rasagiline) was devoid of
      neuroprotective effect in this model system and a rasagiline derivative with a
      double bond in place of the acetylenic propargyl triple bond was much less
      effective. The S(-)-enantiomer of rasagiline was also significantly less active
      than R(+)-rasagiline, as was 6-fluoro rasagiline. Addition of rasagiline (0.1-10
      microM) to cerebellar granule cells grown in medium containing a physiological
      concentration of K(+) did not have an effect on neurite outgrowth as measured by
      synapsin expression level but increased the density of glial cell processes. The
      neuroprotective effects of rasagiline may include a direct action on the neurons
      through inhibition of neuronal death as well as an indirect effect mediated by
      the astrocytes.

PMID- 15721174
TI  - In vivo behavioral effects of stable, receptor-selective neurotensin[8-13]
      analogues that cross the blood-brain barrier.
AB  - A set of neurotensin[8-13] (NT[8-13]) analogues (KK1-19) has been evaluated in
      various pre-clinical assays relevant for further development of these compounds
      as potential antipsychotics. Initial screening of these compounds for induction
      of hypothermia following systemic (I.V.) injection in rats, an indirect method
      commonly utilized to measure the central nervous system (CNS) activity of NT[8
      13] analogues, identified three peptides, KK1, KK13 and KK14, capable of crossing
      the blood-brain barrier (BBB). KK1 features 2(S)-azido-7-aminoheptanoic acid
      (AAHA) in the Arg(8) position and represents the first monosubstituted NT[8-13]
      analogue that crosses the BBB. KK13 and KK14 both feature AAHA in the Arg(8)
      position and tert-Leu in the Ile(12) position while KK14 includes a Trp
      substituted for Tyr(11). When I.P. administered, only the latter two analogues
      induced a significant hypothermic response. KK13 (1mg/kg) inhibited amphetamine
      induced hyperlocomotion after I.P. injection; this assay is highly predictive for
      potential antipsychotics. Chronic dosing (5mg/kg) of this compound over 5
      consecutive days failed to induce hypothermic tolerance while the same dose
      failed to induce measurable catalepsy. KK13 is thus the first NT[8-13] analogue
      described to date that demonstrates inhibition of amphetamine-induced
      hyperlocomotion without inducing catalepsy while maintaining day-to-day
      hypothermic potency.

PMID- 15721175
TI  - Ascorbic acid inhibits ROS production, NF-kappa B activation and prevents ethanol
      induced growth retardation and microencephaly.
AB  - In this study, we established an embryo model to study the effects of ethanol on
      fetal development. When embryos of Xenopus laevis (the African clawed frog) were
      exposed to ethanol, the resultant tadpoles had significantly reduced brain sizes
      (microencephaly) and retarded growth rates. These effects, similar to those
      observed in human fetal alcohol syndrome (FAS), were dose- and time-dependent. We
      further showed that the antioxidant ascorbic acid (vitamin C) could inhibit the
      ethanol-induced reactive oxygen species (ROS) production and NF-kappaB activation
      and protect the ethanol-treated embryos against microencephaly and growth
      retardation. These results suggest the involvement of NF-kappaB and oxidative
      stress in ethanol-mediated developmental defects, and the potential use of
      ascorbic acid as a new and effective protective agent for FAS.

PMID- 15721176
TI  - Brain mitochondrial injury induced by oxidative stress-related events is
      prevented by tamoxifen.
AB  - This study evaluated the effect of the synthetic, nonsteroidal antiestrogen drug
      tamoxifen on the function of brain mitochondria. We observed that tamoxifen
      concentrations above 30 nmol/mg protein induced a slight decrease on RCR and
      ADP/O ratio. However, only higher concentrations of tamoxifen (> or = 70 nmol/mg
      protein) affected the phosphorylative capacity of mitochondria. Those effects
      were characterized by a decrease on mitochondrial transmembrane potential
      (DeltaPsim) and repolarization level and an increase on repolarization lag phase
      with a decrease in ATP levels. Moreover, our results also show that tamoxifen
      presented a potent capacity to inhibit hydrogen peroxide formation and reduced
      the extent of lipid peroxidation induced by the pro-oxidant pair ADP/Fe(2+).
      Tamoxifen also exerted some protection against mitochondrial permeability
      transition pore (MPT) opening, although in a smaller extension than that promoted
      by cyclosporin A, the specific inhibitor of the MPT. However, in the presence of
      tamoxifen plus cyclosporin A, the protection observed was significantly higher
      when compared with that induced by both agents alone. Furthermore, tamoxifen
      avoided the oxidation of thiol groups and GSH depletion promoted by Ca(2+). These
      results show that tamoxifen can afford protection against brain mitochondrial
      injury promoted by several oxidative stress-related events such as hydrogen
      peroxide production, lipid peroxidation and the induction of the MPT. Since
      numerous neurodegenerative diseases are intimately related with mitochondrial
      dysfunction, future therapeutical strategies could be designed taking into
      account this protective role of tamoxifen.

PMID- 15721177
TI  - The dissipation of neuropathic pain paradoxically involves the presence of tumor
      necrosis factor-alpha (TNF).
AB  - Neuropathic pain, a chronic disabling pain arising from nerve injury, develops a
      central component. In brain neurons, tumor necrosis factor-alpha (TNF) levels
      intensify and TNF-inhibition of norepinephrine (NE) release, dependent upon
      alpha(2)-adrenergic activation, amplifies during neuropathic pain onset. TNF
      inhibition of NE release transforms to facilitation in the hippocampus of rats
      administered antidepressants (treat neuropathic pain), contemporaneous with
      decreased neuron TNF. Therefore, adrenergic drugs inhibit increased pain
      sensitivity (hyperalgesia) by decreasing TNF production, thereby inducing
      increased NE release. This study examined TNF- and alpha(2)-adrenergic-regulated
      NE release from hippocampal slices during both the onset and dissipation of
      hyperalgesia during sciatic nerve chronic constriction injury (CCI). The enhanced
      inhibition of NE release by TNF at peak hyperalgesia (day-8) transformed to
      facilitation of NE release at days 12, 14, 16, and 21 post-CCI, corresponding to
      dissipation of hyperalgesia. Chronic antidepressant drug administration alone to
      rats results in similar findings. Rats administered the antidepressant
      amitriptyline (10 mg/kg, i.p., 60 min) at day-8 post-CCI, no longer exhibited
      hyperalgesia. Interestingly, the presynaptic response to TNF transformed to
      facilitation of NE release. While TNF directs the development of hyperalgesia, it
      is also involved in the resolution of pain, a possible mechanism for management
      of chronic pain.

PMID- 15721178
TI  - Profiling at recombinant homomeric and heteromeric rat P2X receptors identifies
      the suramin analogue NF449 as a highly potent P2X1 receptor antagonist.
AB  - P2X receptors are cation channels gated by extracellular ATP and related
      nucleotides. Because of the widespread distribution of P2X receptors and the high
      subtype diversity, potent and selective antagonists are needed to dissect their
      roles in intact tissues. Based on suramin as a lead compound, several derivates
      have been described that block recombinant P2X receptors with orders of magnitude
      higher potency than suramin. Here we characterized the suramin analogue
      4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis
      benzene-1,3-disulfonic acid (NF449) with respect to its potency to antagonize ATP
      or alphabeta-methyleneadenosine 5'-trisphosphate-induced inward currents of
      homomeric rat P2X(1)-P2X(4) receptors or heteromeric P2X(1 + 5) and P2X(2+3)
      receptors, respectively. NF449 most potently blocked P2X(1) and P2X(1 + 5)
      receptors with IC(50) values of 0.3 nM and 0.7 nM, respectively. Three to four
      orders of magnitude higher NF449 concentrations were required to block homomeric
      P2X(3) or heteromeric P2X(2 + 3) receptors (IC(50) 1.8 and 0.3 microM,
      respectively). NF449 was least potent at homomeric P2X(2) receptors (IC(50) 47
      microM) and homomeric P2X(4) receptors (IC(50) > 300 microM). Altogether, these
      results characterize NF449 as the so far most potent and selective antagonist of
      receptors incorporating the P2X(1) subunit such as the P2X(1) homomer and the
      P2X(1 + 5) heteromer.

PMID- 15721179
TI  - Co-activation of the amygdala, hippocampus and inferior frontal gyrus during
      autobiographical memory retrieval.
AB  - Functional MRI was used to investigate the role of medial temporal lobe and
      inferior frontal lobe regions in autobiographical recall. Prior to scanning,
      participants generated cue words for 50 autobiographical memories and rated their
      phenomenological properties using our autobiographical memory questionnaire
      (AMQ). During scanning, the cue words were presented and participants pressed a
      button when they retrieved the associated memory. The autobiographical retrieval
      task was interleaved in an event-related design with a semantic retrieval task
      (category generation). Region-of-interest analyses showed greater activation of
      the amygdala, hippocampus, and right inferior frontal gyrus during
      autobiographical retrieval relative to semantic retrieval. In addition, the left
      inferior frontal gyrus showed a more prolonged duration of activation in the
      semantic retrieval condition. A targeted correlational analysis revealed
      pronounced functional connectivity among the amygdala, hippocampus, and right
      inferior frontal gyrus during autobiographical retrieval but not during semantic
      retrieval. These results support theories of autobiographical memory that
      hypothesize co-activation of frontotemporal areas during recollection of episodes
      from the personal past.

PMID- 15721180
TI  - Impaired intentional content learning but spared incidental retention of
      contextual information in non-demented patients with Parkinson's disease.
AB  - We investigated the incidental and intentional learning performance of 29
      patients with idiopathic Parkinson's disease (PD) and 20 healthy volunteers.
      Measures of incidental and intentional memory were assessed with a spoken verbal
      recall task followed by a temporal word order task, a picture recall task
      followed by a spatial picture location task, and a written word recall task
      followed by a judgement of word frequency task. A multivariate analysis of
      variance and appropriate post hoc tests revealed significant differences for all
      intentional learning variables. In all cases, PD patients performed worse than
      normal controls. No group differences were found for the incidental retention of
      contextual information. The results indicate that PD patients have a selective
      problem of intentional learning, whereas incidental learning of contextual
      information remains intact. Elaborate processing, attentional and organizing
      strategies in the systematic encoding, and recollection of information have been
      attributed to dorsolateral prefrontal activation. Preferential dysfunction of
      dorsolateral prefrontal cortex-associated memory processes is consistent with the
      previously reported uneven patterns of dopamine loss in the striatum of patients
      with idiopathic PD showing most severe dopamine depletion in the portion of the
      caudate nucleus that is anatomically connected to the dorsolateral frontal
      cortex.

PMID- 15721181
TI  - Manual and hemispheric asymmetries in the execution of actual and pantomimed
      prehension.
AB  - Impairments of the ipsilesional hand after brain damage have been reported in
      goal-directed motor acts and in pantomimes; the relationship between both
      movement conditions is largely unknown. In the presented study, pantomimed and
      actual prehension was examined in 29 stroke patients with left brain damage (LBD)
      or right brain damage (RBD) as well as in 21 control subjects. Kinematic analyses
      revealed various performance differences between the conditions of movement
      execution and the subject groups. The differences depended on the hand tested and
      on the side of the brain lesion. During actual prehension deviations from normal
      performance were obvious in the peak velocity of the transport component of the
      movement, which was reduced in RBD patients, and in the duration of the final
      adjustment phase, which was prolonged in both patient groups. Pantomime changed
      various features of movement execution. The transport component was particularly
      altered in the groups performing with the right hand. Hand aperture was
      significantly smaller during pantomime than during actual movement execution in
      all groups. However, this effect was particularly obvious in LBD patients, in
      whom the hand aperture was even completely absent during many of their
      pantomimes. Actual movement execution immediately preceding the pantomimes did
      not change the characteristic features of pantomimes. Thus, the cerebral
      processes for actually executed and pantomimed motor acts differ. Actual
      movements seem to be governed by external affordances and constraints; whereas,
      pantomimes may represent a symbolic act. During prehension, differences in grip
      formation reveal most directly this dichotomy. We argue that the left hemisphere
      plays a special role in the generation of the symbolic act; a lesion may abolish
      grip formation and causes the clinical symptom of apraxia.

PMID- 15721182
TI  - Medial temporal lobe activity for recognition of recent and remote famous names:
      an event-related fMRI study.
AB  - Previous neuroimaging studies examining recognition of famous faces have
      identified activation of an extensive bilateral neural network [Gorno Tempini, M.
      L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al.
      (1998). The neural systems sustaining face and proper-name processing. Brain,
      121, 2103-2118], including the medial temporal lobe (MTL) and specifically the
      hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of
      human memory over decades revealed by functional magnetic resonance imaging.
      Nature Neuroscience, 4, 1139-1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R.,
      Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the
      recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878
      886]. One model of hippocampal functioning in autobiographical, episodic memory
      retrieval argues that the hippocampal complex remains active in retrieval tasks
      regardless of time or age of memory (multiple trace theory, MTT), whereas another
      proposal posits that the hippocampal complex plays a time-limited role in
      retrieval of autobiographical memories. The current event-related fMRI study
      focused on the medial temporal lobe and its response to recognition judgments of
      famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed
      healthy older adults (mean age=70 years). A pilot study with an independent
      sample of young and older subjects ensured that the stimuli were representative
      of a recent and remote time period. Increased MR signal activity was observed on
      a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during
      recognition of familiar names from both the recent and remote time periods when
      compared to non-famous names. However, the impulse response functions in the
      right hippocampus and right PHG demonstrated a differential response to stimuli
      from different time epochs, with the 1990s names showing the greatest MR signal
      intensity change, followed by the 1950s names, followed by foils. The finding
      that recognition of famous names produced significant bilateral MTL activation
      regardless of time epoch relative to foils provides support for the MTT model.
      However, the finding of a temporal gradient in the right MTL also provides
      support for the HC model, given the greater MTL response associated with recently
      famous names relative to remotely famous names.

PMID- 15721183
TI  - Cortical volume and speed-of-processing are complementary in prediction of
      performance intelligence.
AB  - The rationale for the present study was to investigate the relationship between
      cortical volume, the latency of the ERP component P3a (as a measure of speed-of
      processing), and performance intelligence (not adjusted for age differences).
      Seventy-one participants aged 20-88 years underwent a visual 3-stimuli oddball
      ERP task, an MRI-scan, and intelligence testing. P3a latency and cortical volume
      shared 9% variance (p<.05) and both were significantly related to performance
      intelligence (R2=.26 and .40, respectively). The amount of explained variance
      increased significantly (to R2=.51) when both measures were used as simultaneous
      predictors. When a path diagram was constructed including age as an exogenous
      variable, P3a latency and cortical volume both significantly predicted
      performance intelligence, but were no longer related to one another. The main
      conclusion from the study is that speed and size are complementary in prediction
      of performance intelligence, and the theoretical implications are discussed.

PMID- 15721184
TI  - Deficits in temporal-order judgments in dyslexia: evidence from diotic stimuli
      differing spectrally and from dichotic stimuli differing only by perceived
      location.
AB  - The main debate concerning dyslexia focuses on the question of whether dyslexia
      is a language-specific disorder or a general nervous system dysfunction
      manifested in deficits of temporal processing. According to the temporal-order
      deficit hypothesis, dyslexia manifests difficulty in discriminating the temporal
      order of stimuli. Evidence has usually involved testing the ability to
      discriminate series of phonemes or pure tones whose components are separated by
      very short intervals. One of the difficulties in interpreting the data is the
      confound of changes in the spectrum with changes in temporal order. Two
      experiments are reported. In the first experiment, we verified the difficulty by
      adult dyslexics in judging the temporal order of two tones differing in frequency
      and presented diotically. The second experiment was designed to isolate temporal
      order judgment (TOJ) from holistic frequency-based pattern discrimination
      processes. We tested temporal-order judgments with 15 ms duration tones of equal
      frequency presented dichotically (left-right, right-left) with ISI intervals
      ranging from 8 to 400 ms. Dichotic temporal threshold was significantly lower for
      adult normal readers than for the adult dyslexics. The results support the claim
      that adult dyslexics have difficulty in discriminating temporal order even when
      no spectral changes are involved.

PMID- 15721185
TI  - Visuospatial neglect in near and far space: dissociation between line bisection
      and letter cancellation.
AB  - The differential performance on a line bisection and a cancellation task in near
      and far space was studied. A group of 10 patients with severe left-sided
      visuospatial neglect and a group of 10 right-brain damaged patients without
      neglect were examined. The stimuli were presented at a distance of 60 cm (near
      space) and 160 cm (far space), respectively, and corrected for visual angle. In
      the line bisection task, patients were asked to point to the estimated line
      centre with a pencil (near space) or a stick (far space). In the cancellation
      task, patients pointed to all target stimuli they could detect using either a
      pencil (near space) or a stick (far space). Most patients with left hemineglect
      showed a more prominent neglect in far space as compared to near space for the
      line bisection task, whereas no difference of performance between near and far
      space was found in the control patients. In contrast, no group showed a distance
      effect in the cancellation task. The observation that only line bisection is
      influenced by the distance of the stimulus suggests that line bisection and
      cancellation are processed differentially. It is proposed that line bisection
      requires an allocentric reference system focusing attention on objects, whereas
      cancellation tasks are based on an egocentric reference system responsible for
      visuospatial attention. Our results indicate that distance changes perception
      within the allocentric but not within the egocentric system.

PMID- 15721186
TI  - Contributions of occipital, parietal and parahippocampal cortex to encoding of
      object-location associations.
AB  - Events are stored in our episodic memory in varying degrees of accessibility for
      conscious retrieval and combined with varying amounts of associated information.
      A crucial aspect of episodic memory is to bind information together, e.g. linking
      an object to a certain location. Spontaneous or experimenter-induced variance in
      the allocation of attentional resources during encoding critically determines the
      strength of the resulting memory trace especially for associative information as
      measured in subsequent memory tests. The neural correlates of associative memory
      encoding were investigated by lesion, PET- and fMRI-studies. So far no study
      aimed to assess the memory for associative information in a non-categorical way.
      Such a parametric assessment opens the possibility for a closer inspection of the
      relationship between brain activity and memory trace formation. We established a
      novel associative object-location memory paradigm, together with a parametric
      assessment of subsequent memory performance for spatial location which allows:
      (i) to determine if associative information is retrieved in a continuous or
      discontinuous manner during recognition and (ii) to investigate the relationship
      between activity during encoding and the resulting memory trace. Such
      correlations were observed in the occipital, parietal and the parahippocampal
      cortex, areas known to be involved in processing either objects and/or locations.
      The analysis of response functions revealed for the majority of areas involved in
      encoding a continuous relationship between brain activity during encoding and the
      confidence in a subsequent memory test.

PMID- 15721188
TI  - Semantic relevance best predicts normal and abnormal name retrieval.
AB  - The relevance of a semantic feature measures its contribution to the "core"
      meaning of a concept. In a naming-to-description task, we investigated the
      predictive power of relevance in comparison with frequency, familiarity,
      typicality, and Age-of-Acquisition. In a group of Alzheimer patients with
      semantic disorder, relevance turned out to be the best predictor of name
      retrieval accuracy in a naming-to-description task. The same pattern of results
      was observed in normal controls. Relations between semantic relevance and the
      parameters of the concepts are discussed in order to highlight the mechanism of
      concept activation in a naming-to-description task.

PMID- 15721187
TI  - Neural correlates of symbolic and non-symbolic arithmetic.
AB  - Recent evidence suggests that areas in and around the intraparietal sulcus (IPS)
      represent magnitude in a stimulus-independent format. However, it has not been
      established whether the same is true for mental arithmetic or whether activation
      for higher level numerical processing diverges as a function of stimulus format.
      We addressed this question in a functional imaging study by presenting
      participants with simple addition problems using both symbolic (Arabic numerals)
      and non-symbolic (arrays of dots) stimuli. Conjunction analysis revealed common
      neural substrates for symbolic and non-symbolic addition in the anterior IPS
      bilaterally, left posterior IPS, medial frontal gyrus and left precentral gyrus.
      Right parietal and frontal cortex showed greater activation for non-symbolic
      addition. Our results demonstrate that mental arithmetic, studied using addition
      problems, is processed within the IPS independent of stimulus form. Additionally
      we examined whether exact and approximate addition conditions activated different
      neural substrates as a function of stimulus format. We did not find any
      differences between exact and approximate addition using symbolic and non
      symbolic stimuli. This could be due to the inability of the participants to
      suppress exact calculation for single-digit addition problems. In contrast to
      recent findings, we found no significant activation for exact addition condition
      in left, language-related areas.

PMID- 15721189
TI  - Dissociating neuro-cognitive component processes: voxel-based correlational
      methodology.
AB  - Relating behavioural deficits to lesion site has long been an important tool for
      localising the brain bases of cognitive function. Voxel-based methods, based on
      statistical analyses of structural brain images, allow a major step forward in
      the effectiveness of this approach. These methods provide a fine-grained
      assessment of damaged tissue by assigning a continuous value to each voxel over
      the entire brain. This information, correlated with continuous behavioural data
      reflecting specific aspects of cognition, offers new opportunities for
      identifying the neural organisation underlying cognitive function. The research
      reported here demonstrates the ability of this correlational methodology to
      differentiate between the neuro-cognitive components involved in word recognition
      and lexical decision, providing an important new tool for directly linking brain
      areas to specific aspects of psychological performance.

PMID- 15721190
TI  - Interference between number processing and line bisection: a methodology.
AB  - It is usually thought that numbers are represented on a "mental number line" on
      which the progression of smaller to larger numbers occurs from left to right
      suggesting a spatial representation of numbers. Reciprocally, number processing
      has been shown to influence space representation [Fischer, M. (2001). Number
      processing induces spatial performance biases. Neurology, 822-826]. Specifically,
      it was found that when bisecting a string of numbers made up of smaller digits (1
      or 2), the bisection was shifted to the left compared to bisecting a larger digit
      string (8 or 9). In order to avoid any effect of physical difference in stimuli
      Here, we provide a simple methodology to investigate this relationship using a
      task involving the bisection of French number words (e.g."DEUX", "NEUF"). Results
      showed that subjects bisected strings more towards the left for smaller number
      words ("DEUX", 2) than for larger number words ("NEUF", 9), confirming that
      automatic number processing can influence visuo-motor aspects of behaviour.
      Similar results have been obtained with mirror versus canonical presentation,
      indicating that the reading direction is not the crucial factor of this number
      induced bias. In addition, our sample of subjects showed a larger effect for
      number word strings than for Arabic number strings. It is therefore concluded
      that the implicit activation of the left/right side depends on the magnitude of
      the number being embedded within the stimulus lines, irrespective of its actual
      presentation format.

PMID- 15721191
TI  - Deficits in saccadic eye-movement control in Parkinson's disease.
AB  - In contrast to their slowed limb movements, individuals with Parkinson's disease
      (PD) produce rapid automatic eye movements to sensory stimuli and show an
      impaired ability to generate voluntary eye movements in cognitive tasks. Eighteen
      PD patients and 18 matched control volunteers were instructed to look either
      toward (pro-saccade) or away from (anti-saccade) a peripheral stimulus as soon as
      it appeared (immediate, gap and overlap conditions) or after a variable delay;
      or, they made sequential saccades to remembered targets after a variable delay.
      We found that PD patients made more express saccades (correct saccades in the
      latency range of 90-140 ms) in the immediate pro-saccade task, more direction
      errors (automatic pro-saccades) in the immediate anti-saccade task, and were less
      able to inhibit saccades during the delay period in all delay tasks. PD patients
      also made more directional and end-point errors in the memory-guided sequential
      task. Their inability to plan eye movements to remembered target locations
      suggests that PD patients have a deficit in spatial working memory which, along
      with their deficit in automatic saccade suppression, is consistent with a
      disorder of the prefrontal-basal ganglia circuit. Impairment of this pathway may
      release the automatic saccade system from top-down inhibition and produce
      deficits in volitional saccade control. Parallel findings across various motor,
      cognitive and oculomotor tasks suggest a common mechanism underlying a general
      deficit in automatic response suppression.

PMID- 15721192
TI  - The spatial and temporal meanings of English prepositions can be independently
      impaired.
AB  - English uses the same prepositions to describe both spatial and temporal
      relationships (e.g., at the corner, at 1:30), and other languages worldwide
      exhibit similar patterns. These space-time parallelisms have been explained by
      the Metaphoric Mapping Theory, which maintains that humans have a cognitive
      predisposition to structure temporal concepts in terms of spatial schemas through
      the application of a TIME IS SPACE metaphor. Evidence comes from (among other
      sources) historical investigations showing that languages consistently develop in
      such a way that expressions that originally have only spatial meanings are
      gradually extended to take on analogous temporal meanings. It is not clear,
      however, if the metaphor actively influences the way that modern adults process
      prepositional meanings during language use. To explore this question, a series of
      experiments was conducted with four brain-damaged subjects with left perisylvian
      lesions. Two subjects exhibited the following dissociation: they failed a test
      that assesses knowledge of the spatial meanings of prepositions, but passed a
      test that assesses knowledge of the corresponding temporal meanings of the same
      prepositions. This result suggests that understanding the temporal meanings of
      prepositions does not necessarily require establishing structural alignments with
      their spatial correlates. Two other subjects exhibited the opposite dissociation:
      they performed better on the spatial test than on the temporal test. Overall,
      these findings support the view that although the spatial and temporal meanings
      of prepositions are historically linked by virtue of the TIME IS SPACE metaphor,
      they can be (and may normally be) represented and processed independently of each
      other in the brains of modern adults.

PMID- 15721193
TI  - Overt sentence production in event-related fMRI.
AB  - The use of syntactic structures on a sentence level is a unique human ability.
      Functional imaging studies have usually investigated syntax comprehension.
      However, language production may be performed by different neuronal resources. We
      have investigated syntax generation on a sentence level with functional magnetic
      resonance imaging (fMRI). BOLD contrast was measured while subjects articulated
      utterances aloud. In the active condition 'sentence generation' (SG), subjects
      had to produce subject verb object (SVO) sentences (e.g. "The child throws the
      ball") according to syntactically incomplete stimuli (e.g. "throw ball child")
      presented visually. In the control condition 'word reading' (WR), subjects had to
      read identical stimuli without completing the syntactic structure, while in a
      second control condition 'sentence reading' (SR), subjects had to read complete
      sentences. The semantic meaning of all expressions was obvious despite the
      syntactically incomplete structure in conditions SG and WR. In both contrasts, SG
      minus WR and SG minus SR, activation was mainly present in the left inferior
      frontal (BA 44/45) and medial frontal (BA 6) gyri, the superior parietal lobule
      (BA 7) and the right insula (BA 13). A region of interest analysis revealed
      significantly stronger left-dominant activation in BA 45 compared to BA 44. Our
      data illustrates the crucial involvement of the left BA 45 in syntactic encoding
      and is in line with more recent imaging and brain lesion data on syntax
      processing on a sentence level, emphasizing the involvement of a distributed left
      and right hemispheric network in syntax generation.

PMID- 15721194
TI  - Perceptual grouping ability in Williams syndrome: evidence for deviant patterns
      of performance.
AB  - Williams syndrome (WS) is a rare genetic disorder. At a cognitive level, this
      population display poor visuo-spatial cognition when compared to verbal ability.
      Within the visuo-spatial domain, it is now accepted that individuals with WS are
      able to perceive both local and global aspects of an image, albeit at a low
      level. The present study examines the manner in which local elements are grouped
      into a global whole in WS. Fifteen individuals with WS and 15 typically
      developing controls, matched for non-verbal ability, were presented with a matrix
      of local elements and asked whether these elements were perceptually grouped
      horizontally or vertically. The WS group was at the same level as the control
      group when grouping by luminance, closure, and alignment. However, their ability
      to group by shape, orientation and proximity was significantly poorer than
      controls. This unusual profile of grouping abilities in WS suggests that these
      individuals do not form a global percept in a typical manner.

PMID- 15721195
TI  - Sub-acute intoxication by Senna occidentalis seeds in rats.
AB  - Senna occidentalis (So) is a weed that grows in pastures along fences and in
      fields cultivated with cereals such as corn and soybean, and many reports have
      been showing intoxication with this plant in different animal species. It is also
      used in many medicinal purposes. The objective of the present study was to better
      evaluate the toxic effects of prolonged administration of So seeds to rats. Forty
      male Wistar rats were divided into four groups of 10 animals each, three of them
      respectively fed rations containing 1%, 2% and 4% So seeds, and the last one
      (control) fed commercial ration for a period of 2 weeks. Fourteen rats were also
      used in a pair-feeding (PF) experiment. The rats of the experimental groups
      showed lethargy, weakness, recumbency, depression and emaciation. Two rats of the
      4% group and two of the PF group died during the experiment. Histopathological
      study showed fiber degenerations in the skeletal (Tibial, pectoral and diaphragm)
      and cardiac muscles. In the liver parenchyma, was observed vacuolar degeneration
      and, in the kidney, mild nefrosis in the proximal convoluted tubules. All of
      these alterations occurred in a dose-dependent fashion. Moderate to severe
      degeneration and spongiosis in the central nervous system, especially in
      cerebellum. Electron microscopy revealed mitochondrial lesions in all analyzed
      tissues.

PMID- 15721196
TI  - Maternal exposure to androstenedione does not induce developmental toxicity in
      the rat.
AB  - Thirty-day old female rats received corn oil or androstenedione (in corn oil) at
      one of four concentrations (5.0, 10.0, 30.0 or 60.0 mg/kg body weight) by gavage
      for two weeks prior to mating, during the mating period and until gestation day
      (GD) 19. Caesarean sections were performed on GD 20. No dose related changes were
      observed in serum androstenedione, estradiol, LH, FSH, testosterone or
      progesterone. A statistically significant decrease in estrous cycle length was
      observed in the 60.0 mg/kg dose group only. Feed and fluid consumption, mean body
      weight gain, organ weight and fetal parameters were not affected by
      androstenedione treatment. At the doses given, androstenedione had no specific
      effect on the development of individual bones or soft tissues.

PMID- 15721197
TI  - Inhibitory effects of volatile antioxidants found in various beans on
      malonaldehyde formation in horse blood plasma.
AB  - The inhibitory effect of aroma extracts isolated from dried soybeans, mung beans,
      kidney beans, and azuki beans on malonaldehyde (MA) formation from horse blood
      plasma oxidized with Fenton's reagent was determined by gas chromatography (GC)
      coupled with nitrogen-phosphorus detector (NPD). Aroma chemicals such as maltol,
      eugenol, benzyl alcohol, 1-octen-3-ol, butyrolactone, and 1-methyl-2-pyrrolidone,
      found in the aroma extracts of beans, were also examined for their inhibitory
      effect on the same system. Among the four aroma extracts tested, the aroma
      extract of soybeans exhibited the strongest antioxidant activity. Extracts of
      soybeans, mung beans, azuki beans, and kidney beans inhibited MA formation by
      58%, 47%, 40%, and 23%, respectively, at the level of 400 microg/mL, whereas,
      alpha-tocopherol and BHT inhibited MA formation by 52% and 70%, respectively, at
      the same level. Among the tested aroma chemicals, the antioxidant activity
      decreased in the following order: eugenol>maltol>1-octen-3-ol>benzyl
      alcohol>butyrolactone>1-methyl-2-pyrrolidone.

PMID- 15721198
TI  - Characterization of antimutagenic mechanism of 3-allyl-5-substituted 2
      thiohydantoins against 2-amino-3-methylimidazo[4,5-f]quinoline.
AB  - 3-Allyl-5-substituted 2-thiohydantoins (ATH-amino acids) derived from allyl
      isothiocyanate and amino acids can inhibit the mutagenicity of 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ) in the Salmonella assay. In this report, we
      studied possible mechanisms for the inhibition using rat liver S9 in assays for
      ethoxyresorufin O-deethylase (EROD), a marker activity for cytochrome P450 1A
      (CYP1A), which activates heterocyclic amines, and the Salmonella assays with the
      direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy
      IQ). Quantitative analysis of ATH-amino acids and IQ during incubation with rat
      liver S9 fraction by HPLC showed that ATH-amino acids could act as S9-inhibitors,
      thereby inhibiting metabolic activation of IQ. Among the tested ATH-amino acids,
      ATH-Phe, ATH-Trp, ATH-Leu and ATH-Val showed a dose-dependent inhibition of EROD
      activity. ATH-Gly, ATH-Glu, and ATH-Asp behaved as blocking agents toward N
      hydroxy-IQ, but exhibited no inhibition of EROD activity.

PMID- 15721199
TI  - Comprehensive analysis of the effect of phytoestrogen, daidzein, on a testicular
      cell line, using mRNA and protein expression profile.
AB  - In this study, we examined the effects of exposure to phytoestrogen (daidzein),
      17beta-estradiol (E2), diethylstilbestrol (DES) and staurosporin on the TM4
      testicular cell line, using comprehensive analysis, such as cDNA microarray and
      two-dimension polyacrylamide gel electropholesis (2D-PAGE) analysis, and we
      demonstrated if these toxicogenomic analyses could classify the chemical
      compounds. First, RNA was extracted from TM4 cells that had been treated with
      daidzein (80 microM), DES, E2 (40 microM) and stauroporin (100 nM) for 30 min. We
      performed cDNA microarray analysis, and the expression ratio data thus obtained
      were then analyzed using hierarchical clustering. This hierarchical clustering
      showed that daidzein exposure induced a different effect on gene expression
      change from that of E2, DES and staurosporin. Next, protein extracted from TM4
      cells also underwent cDNA microarray analysis for 3 h. We performed 2D-PAGE
      analysis, and the spot intensity ratio data thus obtained were analyzed using
      hierarchical clustering. As with cDNA microarray, the hierarchical clustering of
      protein spot ratios showed that daidzein exposure induced a different effect on
      gene expression change from that of the other substances. In conclusion, we have
      demonstrated for the first time that classification of these chemicals can be
      performed by clustering analysis, using data from cDNA microarray and 2D-PAGE
      analyses, and that exposure to daidzein induces effects different from those of
      E2, DES and staurosporin.

PMID- 15721200
TI  - Effects of oral androstenedione on steroid metabolism in liver of pregnant and
      non-pregnant female rats.
AB  - It is unknown whether androstenedione, a steroidal dietary supplement taken to
      enhance athletic performance, can affect physiological hormone levels by altering
      liver enzyme activities that metabolize steroid hormones. Altered hormone levels
      could be especially devastating during pregnancy. Mature female rats were gavaged
      with 0, 5, 30 or 60 mg/kg/day androstenedione beginning two weeks prior to mating
      and continuing through gestation day 19. Non-pregnant female rats were gavaged
      over the same time frame with 0 or 60 mg/kg/day androstenedione. Livers were
      removed from dams on gestation day 20 and from non-pregnant rats after five
      weeks' treatment. Liver microsomes were incubated with 200 microM testosterone,
      and the reaction products were isolated and analyzed by HPLC. In pregnant rats,
      formation of 6alpha-, 15beta-, 7alpha-, 16beta-, and 2beta-hydroxytestosterone
      was increased significantly vs. control at the highest dose level only. Formation
      of 6beta-hydroxytestosterone increased significantly at both the 30 and 60
      mg/kg/day dose levels. In non-pregnant rats, 60 mg/kg/day androstenedione
      significantly increased formation of 15beta-, 6beta-, 16beta-, and 2beta
      hydroxytestosterone. The data suggest that high oral doses of androstenedione can
      induce some female rat liver cytochromes P450 that metabolize steroid hormones
      and that the response to androstenedione does not differ between pregnant and non
      pregnant female rats.

PMID- 15721201
TI  - Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated
      by supercritical carbon dioxide.
AB  - Supercritical carbon dioxide (SC-CO2) was used as the elution solvent for
      fractioning ethanolic extract (E) of Cordyceps sinensis (CS), a traditional
      Chinese herbal remedy, into R, F1, F2, and F3 fractions. This extractive
      fractionation method is amenable to large scale and is nontoxic. These four
      fractions were characterized in terms of total polysaccharides and cordycepin
      concentrations, scavenging ability of free radicals, and anti-tumor activities.
      Experimental results demonstrated that fractionation altered the distributions of
      total polysaccharides and cordycepin in fractions. Fraction R was the most active
      fraction to scavenge free radicals and inhibit the proliferation of carcinoma
      cells, followed by the fraction F1 and the extract E. The effect of scavenging on
      1,1-diphenyl-2-picryl hydrazyl (DPPH) of CS extract and fractions at 2 mg/ml was
      R (93%), F1 (75%), E (66%), F2 (47%), and F3 (27%). The IC50 (50% cell growth
      inhibitory concentration) of tumor cell proliferation and colony formation on
      human colorectal (HT-29 and HCT 116) and hepatocellular (Hep 3B and Hep G2)
      carcinoma cells by fraction R were around 2 microg/ml. Conversely, R did not
      affect the growth of normal dividing human peripheral blood mononuclear cells
      (PBMC) by exhibiting a large value of IC50 over 200 microg/ml. Accumulation of
      tumor cells at sub-G1 phase and the fragmentation of DNA, typical features of
      programmed cell death, were observed in a time and dose dependent manner.
      Scavenging of free radicals and anti-cancer activity (value of IC50) correlated
      closely with the quantities of polysaccharides (Spearman's rho=0.901 and -0.870,
      respectively). Taken together, our findings suggest that fraction R, obtained by
      SC-CO2 fluid extractive fractionation, showed strong scavenging ability and
      selectively inhibited the growth of colorectal and hepatocellular cancer cells by
      the process of apoptosis.

PMID- 15721202
TI  - Residual behaviour of profenofos on some field-grown vegetables and its removal
      using various washing solutions and household processing.
AB  - Profenofos (Selecron 72% EC), was sprayed on field-grown pepper and eggplant at
      the recommended rate of 1.28 kg a,i/ha. Fruit samples were collected at 1 h to 14
      days after application and analysed to determine the content and dissipation rate
      of profenofos. The effect of different washing solutions and some household
      processing on the removal of such residues from treated vegetables were also
      investigated. Profenofos residues were quantified by using gas chromatography.
      The results showed that the consumable safety time were found to be 10 days on
      sweet pepper and 14 days on hot pepper and eggplant fruits. The initial
      disappearance of profenofos appeared to follow first order kinetics with
      different rates of reaction of 0.38, 0.40 and 0.35 day(-1) for hot pepper, sweet
      pepper and eggplant, respectively. The corresponding half-lives (t1/2) were 1.84,
      1.74 and 1.96 days. Also, the results indicated that tap water, potassium
      permenganate and acetic acid solution gave high percent removal of profenofos
      residues from hot and sweet pepper fruits, while no detectable residues was found
      in eggplant fruit after washing with soap and acetic acid solutions. In general,
      all tested washing solutions gave higher percent removal of profenofos residues
      from eggplant fruit than the two other pepper fruits. Blanching and frying of
      pepper and eggplant fruits resulted in great reduction to almost completely
      removed (approximately 100%) of the deposited profenofos. In addition, pickling
      process removed 92.58 and 95.61% from hot pepper fruit after one week and after
      two weeks, respectively.

PMID- 15721203
TI  - Study on tobacco components involved in the pyrolytic generation of selected
      smoke constituents.
AB  - The aim of this study was to investigate the contribution of various tobacco
      components to the generation of smoke constituents using a tobacco pyrolysis
      model. We analyzed the amounts of primary tobacco components (sugars, protein,
      polyphenols, alkaloids, organic acids, inorganics etc.) in flue-cured and burley
      tobacco leaves. Each of the components was added to the tobacco leaves at the 0.5
      fold and 1.0-fold amount naturally present in the leaves. The treated tobacco
      samples were pyrolyzed at 800 degrees C in a nitrogen atmosphere with an infrared
      image furnace, and the selected smoke constituents (benzo[a]pyrene, hydrogen
      cyanide, carbonyl compounds, aromatic amines, volatile organic compounds and
      phenolics) were quantitatively analyzed by several methods, including high
      performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry
      (GC-MS). The contribution of each tobacco component to the generation of selected
      smoke constituents was estimated from a regression line determined by the three
      yields (no addition, 0.5-fold addition, and 1.0-fold addition). The results of
      this study can provide useful and comprehensive information on the relationship
      between tobacco components and selected smoke constituents during pyrolysis.

PMID- 15721204
TI  - Induction of micronuclei and binuclei in blood, gill and liver cells of fishes
      subchronically exposed to cadmium chloride and copper sulphate.
AB  - Common carp (Cyprinus carpio), Prussian carp (Carassius gibelio) and Peppered
      cory (Corydoras paleatus) were evaluated as target species to perform
      genotoxicity tests for heavy metals. Fishes were exposed to different doses of
      cadmium (0.005-0.1 mg/L) and copper (0.01-0.25 mg/L) for 21 days. Hexavalent
      chromium at a single dose of 5 mg/L was used as a positive control. Frequencies
      of micronuclei and binuclei were evaluated comparatively in peripheral blood
      erythrocytes, gill epithelial cells and liver cells. As a result it was observed
      that, fish species and their tissues showed differential sensitivity to the heavy
      metal treatment. In general, frequencies of micronucleated and binucleated cells
      significantly increased following the exposure for 21 days to copper, cadmium and
      chromium. On the other hand, gill and liver cells showed higher frequencies of
      micronuclei and binuclei than erythrocytes. Our results indicated the formation
      of micronuclei and binuclei in fish cells caused by their exposure to cadmium,
      copper and chromium, thus verifying results obtained earlier on mammals, which
      indicated that these heavy metals have cytotoxic and genotoxic effects. The
      suitability of the micronucleus assay in native fish species for the screening of
      aquatic genotoxicants is highlighted and the importance of target tissue
      selection in the piscine micronucleus test is emphasized.

PMID- 15721205
TI  - Acute and subchronic toxicity studies of cryogenically-frozen, cryomilled,
      Pelodiscus sinensis (Japanese soft-shelled turtle--suppon) powder administered to
      the rat.
AB  - Sprague-Dawley rats received "cryogenically-frozen suppon" (CFS), a cryomilled
      product derived for the Japanese soft-shelled turtle (Pelodiscus sinensis),
      widely consumed for its nutritious value and medicinal properties, especially for
      the maintenance of normal blood pressure and insulin levels, and in women for the
      treatment of menopausal symptoms. In this acute study, a single limit dose of 2.0
      g/kg was given po. common to 10 male and 10 female rats. No adverse effects or
      mortality were observed during a 14-day period and at gross pathological
      examination. In the subchronic study, CFS was administered as oral daily doses of
      100, 350, and 1000 mg/kg administered for 97 days, resulting in no mortality, no
      changes in body weight, food and water consumption, hematological and serum
      chemistry parameters, organ weights, or gross pathology or histopathology. The
      only treatment related finding was a characteristic excited behavior observed in
      several male rats from the second or third week of treatment, distributed evenly
      in all male treatment groups but not affecting all males. The number of excited
      animals did not change over time, the syndrome occurred in all test item treated
      male groups with similar incidence. None of the females was so affected.

PMID- 15721206
TI  - Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP)
      in a cross-mating toxicity study of mice.
AB  - Bis(2-ethylhexyl) phthalate (DEHP) was given in the diet to provide levels of 0%
      (C) or 0.03% (T) from 5 weeks of age of the F0 generation to 9 weeks of age of
      the F1 generation in mice. At 9 weeks of age, each female was paired with one
      male from the same or another treatment groups (cross-mating: C/C, T/C, C/T,
      T/T), for a period of 5 days. The selected reproductive and neurobehavioural
      parameters were measured. There were no adverse effects of DEHP on either litter
      size, litter weight and sex ratio at birth. The average body weight of female
      offspring was significantly affected in group IV (T/T) at PND 14. In behavioural
      developmental parameters, swimming direction at PND 4 was significantly
      accelerated in group III (C/T) in female offspring. In movement activity of
      exploratory behaviour at 3 weeks of age, number of movement of male offspring was
      significantly affected in group IV (T/T). The dose level of DEHP in the present
      cross-mating study produced few adverse effects in reproductive and
      neurobehavioural parameters in mice.

PMID- 15721207
TI  - Inhibition of benzo[a]pyrene induced mutagenicity and genotoxicity by black tea
      polyphenols theaflavins and thearubigins in multiple test systems.
AB  - This study investigated the antimutagenic and anticlastogenic effects of black
      tea polyphenols, theaflavins (TF) and thearubigins (TR) in Salmonella assay in
      vitro and in vivo in bone marrow cells of mice as measured by chromosomal
      aberrations (CA) and sister chromatid exchange (SCE) against a known carcinogen,
      benzo[a]pyrene (B[a]P). A significant decrease in mutagenicity in Salmonella
      assay and both CA and SCE were observed in all the different concentrations of TF
      and TR plus B[a]P treated series when compared with B[a]P treated group alone.
      These results indicate that both TF and TR have significant antimutagenic and
      anticlastogenic effects.

PMID- 15721208
TI  - Effect of sulfite on macrophage functions of normal and sulfite oxidase-deficient
      rats.
AB  - Sulfite has both an endogenous and an exogenous provenance in the mammalian
      tissues. The aim of the present study was to assess the effect of sulfite on
      macrophages functions in normal or sulfite oxidase deficient rats. Rats were
      divided into eight groups; (1) control group, (2) sulfite group (the rats
      received sodium meta bi-sulfite (25 mg/kg) in drinking water for 6 weeks), (3)
      vitamin E group (the rats received Vit E (50 mg/kg) by gavage for 6 weeks), (4)
      sulfite group+Vit E, (5)sulfite oxidase deficient group (the rats received high
      W/Mo-deficient diet. The activity of sulfite oxidase was reduced in rats
      maintained on the high-W/Mo-deficient diet during the first 21 days of treatment.
      After the sulfite-oxidase deficiency, the rats continued to receive high-W/Mo
      deficient diet for 6 weeks.), (6) sulfite+sulfite oxidase deficient group, (7)
      Vit E+sulfite oxidase deficient group, and (8) sulfite+Vit E+sulfite oxidase
      deficient group. Sulfite caused a significant increase in phagocytic and
      chemotactic activities of peritoneal macrophages. In sulfite-oxidase deficient
      rats, the increase in phagocytic and chemotactic activities in peritoneal
      macrophages after sulfite intake was found more than the control rats. Vit E
      supplementation prevented sulfite induced increase in macrophages functions.
      These results show that the macrophage functions are sensitive to sulfite intake.
      The effect of sulfite on macrophage functions may be related to reactive oxygen
      species. Because Vit E administration was able to modulate significantly sulfite
      induced changes in the functions of peritoneal macrophages.

PMID- 15721209
TI  - Effects of aflatoxin B1 on embryo fetal development in rabbits.
AB  - Aflatoxin B1 (AFB1), is a food borne mycotoxin produced by fungal species of the
      genera Aspergillus. To elucidate the teratogenic effects, AFB1 was dissolved in
      corn oil and given orally to New Zealand White rabbits during 6-18 days of
      gestation with the dose levels of 0.025, 0.05 and 0.1 mg/kg body weight. To
      assess pathomorphological features of the anomalies induced by AFB1, the fetal
      serial sections were histologically examined. There was no maternal mortality in
      any group. There was non-significant decrease in percent of live fetuses and
      increase in the percent resorptions and post-implantation losses at 0.1 mg/kg
      dose group as compared with those of controls. The mean crown to rump lengths of
      0.05 and 0.1 mg/kg dose groups were significantly reduced than that of the
      control. The mean fetal weights were significantly reduced in 0.1 mg/kg dose
      group than that of other treated groups. The gross anomalies observed included
      wrist drop and enlarged eye socket whereas, skeletal anomalies were agenesis of
      caudal vertebrae, incomplete ossification of skull bones and bent metacarpals.
      The visceral anomalies of microphthalmia and cardiac defects were seen at 0.1
      mg/kg dose group. The characteristic histological findings of fetal tissues were
      distortion of normal hepatic cord pattern and reduced megakaryocytes in liver,
      fusion of auriculo-ventricular valves, mild degenerative changes in myocardial
      fibers, microphthalmic eyes and lenticular degeneration. The results of this
      study indicated that AFB1 was found to be teratogenic in rabbits when given by
      oral route during gestation days 6-18 and the dose of 0.1 mg/kg could be
      considered as the minimum oral teratogenic dose. The histological examination of
      the fetal tissues indicated its importance in identifying the visceral anomalies
      which were otherwise not visible.

PMID- 15721210
TI  - Cholesterol-3-beta, 5-alpha, 6-beta-triol induced genotoxicity through reactive
      oxygen species formation.
AB  - The mutagenicity of oxysterols, cholesterol-3beta,5alpha,6beta-triol (alpha
      Triol), 7-keto-cholesterol (7-Keto) and cholesterol-5alpha,6alpha-epoxide (alpha
      Epox) were examined by the Ames method and chromosome aberration test in this
      study. Only alpha-Triol concentration-dependently caused an increase of bacterial
      revertants in the absence of metabolic activating enzymes (S9), but not 7-keto
      and alpha-Epox. The mutagenic effect of alpha-Triol was reduced by the addition
      of S9. On the other hand, although alpha-Triol significantly induced chromosome
      aberration in CHO-K1 cells with and without S9. However, the addition of S9
      reduced the degree of abnormal structure chromosome compared to without S9 mix.
      Catalase and superoxide dismutase (SOD) inhibited alpha-Triol induced increase of
      revertants in Salmonella typhimurium and chromosome aberration frequency in CHO
      cells, suggesting that reactive oxygen species (ROS) might be involved in the
      genotoxic effect of alpha-Triol. Treatment with alpha-Triol increased the ROS
      production in CHO cells, which could be attenuated by catalase and SOD. Results
      in this study suggested, for the first time that alpha-Triol, causes genotoxic
      effect in an ROS-dependent manner.

PMID- 15721211
TI  - Characterization of the effect of deoxynivalenol on selected male reproductive
      endpoints.
AB  - The effect of deoxynivalenol (DON) exposure on male reproductive function was
      assessed in the rat. Male rats were divided into a control group (n=15 rats) and
      four treatment groups (0.5 mg/kg, n=15; 1.0 mg/kg, n=15; 2.5 mg/kg, n=15; and 5.0
      mg/kg DON, n=16) and exposed to DON daily for 28 days via gastric intubation.
      Both body weight gain and the final body weight of animals in the 5.0 mg/kg dose
      group and feed consumption in animals in the 2.5 mg/kg and 5.0 mg/kg dose groups
      were significantly reduced compared to controls. Fluid consumption was not
      affected in any of the treated groups. Epididymal and seminal vesicle weights
      expressed per gram of body weight and brain weight were significantly reduced,
      compared to control weights, in animals from the 2.5 and 5.0 mg/kg dose groups
      while prostate weight expressed per gram of brain weight and body weight was
      significantly lower than controls only in the 5.0 mg/kg dose group. A
      statistically significant, dose-related decrease in homogenization resistant
      testicular spermatid counts, spermatid numbers, absolute cauda epididymal sperm
      numbers and cauda epididymal sperm numbers per gram of cauda epididymis was
      observed in the 5.0 mg/kg DON treatment group. Sperm tail abnormalities (broken
      tails) in the 5.0 mg/kg dose group were significantly higher than in the control
      group. Sperm swimming speed (VSL and VCL) was significantly increased only in the
      2.5 mg/kg dose group. Serum FSH and LH concentrations were increased in a dose
      dependent manner across all treated groups while serum testosterone
      concentrations were decreased in a dose-related manner across all dose groups. An
      increase in germ cell degeneration, sperm retention and abnormal nuclear
      morphology was observed in the 2.5 mg/kg and 5.0 mg/kg dose groups. Treatment
      related effects included lesions in the non-glandular stomach, thymic lymphoid
      depletion and splenic hematopoiesis in the 5.0 mg/kg treatment group.

PMID- 15721212
TI  - Association of striatal dopamine D2/D3 receptor binding potential with pain but
      not tactile sensitivity or placebo analgesia.
AB  - Striatal dopamine D2/D3 receptors have been suggested to play a role in pain
      sensitivity and placebo effect. We studied whether the association of dopamine
      D2/D3 receptor binding potential (BP) with sensory thresholds is specific to the
      modality of pain, and whether striatal dopamine D2/D3 receptor BP predicts the
      magnitude of placebo analgesia. Pain and tactile thresholds, and placebo
      analgesia were assessed in eight healthy human male subjects who had previously
      participated in a dopamine D2/D3 receptor positron emission tomography study with
      [11C]raclopride. The results show that the cutaneous heat pain threshold was
      inversely correlated with dopamine D2/D3 receptor BP in the right putamen, but
      responses to tactile stimulation did not correlate with striatal dopamine D2/D3
      receptor BP. Placebo-induced elevation of the heat pain threshold did not
      correlate with striatal dopamine D2/D3 receptor BP. These results suggest that
      the influence of striatal dopamine D2/D3 receptors on sensory thresholds is
      selective for the modality of pain. Moreover, striatal dopamine D2/D3 receptor BP
      appears not to predict individual's analgesic response to placebo.

PMID- 15721213
TI  - EEG coherence in early-blind humans during sound localization.
AB  - Human blind individuals have demonstrated cross-modal plasticity in research over
      the past decade. In one such study, we showed that early-blind subjects were able
      to localize sound sources accurately despite the lack of visual input for the
      calibration of their auditory space. A further ERP study with these subjects also
      revealed N1 and P3 components during a sound localization task to be more
      posteriorly distributed than for sighted controls, indicating an involvement of
      posterior regions in sound localization for blind subjects not present for
      sighted subjects. In the current study, we analyzed these data for EEG power and
      coherence in theta, alpha, beta, and gamma frequency bands to see whether blind
      individuals would show increased coherence reflecting increased connectivity
      between the central and posterior cortical regions. Blind and sighted subjects
      did not differ with respect to overall EEG power in any frequency range. However,
      EEG coherence was significantly increased in blind subjects compared to sighted
      in the theta, alpha, and beta frequency bands. These results have implications
      for cortical plasticity affected by sensory deprivation in humans.

PMID- 15721214
TI  - Modulation of short-term social memory in rats by adenosine A1 and A(2A)
      receptors.
AB  - The recognition of an unfamiliar juvenile rat by an adult rat has been shown to
      imply short-term memory processes. The present study was designed to examine the
      role of adenosine receptors in the short-term social memory of rats using the
      social recognition paradigm. Adenosine (5.0-10.0 mg/kg), the selective adenosine
      A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.025-0.05 mg/kg) and
      the selective adenosine A(2A) receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2
      methylphenyl)ethyl]adenosine (DPMA, 1.0-5.0 mg/kg), given by i.p. route 30 min
      before the test, disrupted the juvenile recognition ability of adult rats. This
      negative effect of adenosine (5.0 mg/kg, i.p.) on social memory was prevented by
      pretreatment with the non-selective adenosine receptor antagonist caffeine (10.0
      mg/kg, i.p.), the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine
      (DPCPX, 1.0 mg/kg, i.p.) and the adenosine A(2A) antagonist 4-(2-[7-amino-2-{2
      furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385,
      1.0 mg/kg, i.p.). Furthermore, acute administration of caffeine (10.0-30.0 mg/kg,
      i.p.), DPCPX (1.0-3.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.) improved the
      short-term social memory in a specific manner. These results indicate that
      adenosine modulates the short-term social memory in rats by acting on both A1 and
      A(2A) receptors, with adenosine receptor agonists and antagonists, respectively,
      disrupting and enhancing the social memory.

PMID- 15721215
TI  - Developmental status of neurons selectively vulnerable to rapidly triggered post
      ischemic caspase activation.
AB  - Caspase activation occurs within 1h of reperfusion in discrete cell populations
      of the adult rat brain following transient forebrain ischemia. Based on the
      proximity of these cells to regions of adult neurogenesis and the known
      susceptibility of developing neurons to apoptosis, we tested the hypothesis that
      rapidly triggered post-ischemic caspase activation occurs in immature neurons or
      neuroprogenitor cells. Adult male Long Evans rats were injected with BrdU to
      label mitotic cells 1, 7, or 28 days prior to being studied. Rats were then
      subjected to either sham surgery or 10-min transient forebrain ischemia. At 1h
      after reperfusion, rats underwent perfusion fixation and brains prepared for
      immunohistochemical analysis. Immunolabeling for caspase-substrate cleavage,
      using an antibody directed at the caspase derived fragment of alpha-spectrin, was
      observed in discrete cell populations of the rostral dentate gyrus, dorsal
      striatum, extreme paramedian CA1 hippocampus, indusium gresium, olfactory
      tubercle, and thalamus. No cells double-labeled for caspase-substrate cleavage
      and BrdU at any time point after BrdU injection. Furthermore, cells immunolabeled
      for caspase-substrate cleavage did not double-label for markers of immature
      neurons (doublecortin) or progenitor cells (nestin), but did double-label for the
      mature neuronal marker NeuN. These results indicate that the phenomenon of
      rapidly triggered caspase activation in the adult rat brain after transient
      forebrain ischemia is specific to mature neurons and does not occur in
      neuroprogenitor cells or immature neurons.

PMID- 15721216
TI  - Role of MAPK/ERK1/2 in the glucose deprivation-induced death in immunostimulated
      astroglia.
AB  - Recently we have reported that glucose deprivation induces the potentiated death
      and loss of ATP in immunostimulated astroglia via the production of NO and
      eventually peroxynitrite. This study examined the role of the ERK1/2 signaling
      pathways in the glucose deprivation-induced death of immunostimulated astroglia.
      Immunostimulation with LPS+IFN-gamma induced the sustained activation of ERK1/2
      for up to 48 h. Glucose deprivation caused the loss of ATP and consequently cell
      death in immunostimulated astroglia, which was significantly blocked by the
      treatment with the ERK kinase (MEK1) inhibitor, PD98059 (10-40 microM), to
      inhibit the ERK1/2 pathways. The systems for generating NO (iNOS) or superoxide
      (NADPH oxidase) were regulated by the ERK1/2 signaling pathways because the
      addition of PD98059 reduced the level of both. Interestingly, glucose deprivation
      caused an approximately two-fold increase in the level of peroxynitrite formation
      in immunostimulated astroglia, which was significantly reduced by the PD98059
      treatment. This demonstrates that the ERK1/2 signaling pathways play an important
      role in glucose deprivation-induced death in immunostimulated astroglia by
      regulating the generation of NO, superoxide and their reaction product,
      peroxynitrite.

PMID- 15721217
TI  - A double blind study showing that two weeks of daily repetitive TMS over the left
      or right temporoparietal cortex reduces symptoms in patients with schizophrenia
      who are having treatment-refractory auditory hallucinations.
AB  - The aim of this study was to evaluate the effect of repetitive transcranial
      magnetic stimulation (rTMS) on the left and right temporoparietal cortex compared
      with sham stimulation in schizophrenic patients with treatment-refractory
      auditory hallucinations (AH). Thirty-nine patients with schizophrenia with
      treatment-refractory AH were allocated randomly to one of three groups: daily
      left, right, and sham rTMS groups. rTMS was applied to the TP3 or 4 regions with
      the aid of the electroencephalography 10-20 international system at 1 Hz for 20
      min per day for 10 treatment days. Symptoms were evaluated using the Auditory
      Hallucination Rating Scale (AHRS), the Positive and Negative Symptoms Scale
      (PANSS), the Clinical Global Impression--Severity (CGI-S), and Clinical Global
      Impression--Improvement (CGI-I) scale. For the time effect (within-subject
      comparison), there were significant changes in the frequency of AHs, positive
      symptoms of PANSS, and CGI-I. A between-group comparison revealed significant
      differences in the positive symptoms of PANSS, and CGI-I scores. Post hoc
      analysis revealed that both the right- and left-side rTMS treatment groups
      exhibited better CGI-I scores compared to the sham-stimulated group. This study
      suggests that 10 days of low-frequency rTMS applied daily for 20 min to either
      temporoparietal cortex significantly reduces the symptoms in patients with
      schizophrenia who are having refractory AH, but the left sided rTMS is not
      superior to right or sham rTMS.

PMID- 15721218
TI  - A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not
      associate with either methamphetamine dependence or schizophrenia.
AB  - Genetic contributions to the etiology of substance abuse and dependence are
      topics of major interest. Acute and chronic cannabis use can produce drug-induced
      psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia.
      The endocannabinoid system is one of the most important neural signaling pathways
      implicated in substance abuse and dependence. The fatty acid amide hydrolase
      (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible
      involvement of FAAH in the etiology of methamphetamine dependence/psychosis or
      schizophrenia, we examined the genetic association of a nonsynonymous
      polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no
      significant association in allele and genotype frequencies of the polymorphism
      with either disorder. Because the Pro129Thr polymorphism reduces enzyme
      instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid
      system induce susceptibility to either methamphetamine dependence/psychosis or
      schizophrenia.

PMID- 15721219
TI  - Increased facilitation of the primary motor cortex following 1 Hz repetitive
      transcranial magnetic stimulation of the contralateral cerebellum in normal
      humans.
AB  - Connections between the cerebellum and the contralateral motor cortex are dense
      and important, but their physiological significance is difficult to measure in
      humans. We have studied a group of 10 healthy subjects to test whether a
      modulation of the excitability of the left cerebellum can affect the excitability
      of the contralateral motor cortex. We used repetitive transcranial magnetic
      stimulation (rTMS) at 1 Hz frequency to transiently depress the excitability of
      the left cerebellar cortex and paired-pulse TMS testing of intracortical
      inhibition (ICI) and intracortical facilitation (ICF) to probe the excitability
      of cortico-cortical connections in the right motor cortex. The cortical silent
      period was also measured before and after cerebellar rTMS. Motor evoked
      potentials (MEPs) were significantly larger after than before conditioning rTMS
      trains (p < 0.01). Moreover, left cerebellar rTMS increased the ICF of the right
      motor cortex as measured with paired-pulses separated by an interstimulus
      interval (ISI) of 15 ms. The effect lasted for up to 30 min afterward and was
      specific for the contralateral (right) motor cortex. The cortical silent period
      was unaffected by cerebellar rTMS. The implication is that rTMS of the cerebellar
      cortex can shape the flowing of inhibition from Purkinje cells toward deep
      nuclei, thereby increasing the excitability of interconnected brain areas.

PMID- 15721220
TI  - Hypoxia-ischemic insult in neonatal rats induced slowly progressive brain damage
      related to memory impairment.
AB  - The present study was designed to determine potential associations between the
      brain damage induced by hypoxic-ischemic (HI) insult and spatial learning
      impairment in an eight-arm radial maze task. We first determined the pathological
      outcomes after 2, 5, 9, and 17 weeks of recovery following the HI insult. The
      results show that the brain damage progressed from 2 up to 17 weeks of recovery.
      To clarify the time course of the brain damage changes, we investigated the
      histological changes of the same individual with magnetic resonance imaging (MRI)
      after 5, 9, and 57 weeks of recovery following the HI insult. The MRI changes
      were similar to the histological changes, and the brain damages were exacerbated
      in the contralateral hemisphere after 57 weeks of recovery following the HI
      insult. To investigate whether alteration in brain function was correlated with
      MRI and histological changes, the rats were made to find their way through an
      eight-arm radial maze was performed at either 7th or 16th weeks of recovery.
      According to the results, the spatial learning impairments of rats in the maze
      starting at 16 weeks of recovery were more severe than those at 7 weeks of
      recovery, indicating that the impairments were progressive and depended on the
      degree of brain damage. The results of the present study are the first
      demonstration that the evolutional and specific brain damage following the HI
      insult is slowly and progressively exacerbated to the contralateral hemisphere
      and rats who experience the HI are at risk for showing a late impairment of brain
      function.

PMID- 15721221
TI  - Overlap in the distribution of TrkB immunoreactivity and retinohypothalamic tract
      innervation of the rat suprachiasmatic nucleus.
AB  - Brain-derived neurotrophic factor (BDNF) may regulate the circadian sensitivity
      of the clock in the hypothalamic suprachiasmatic nucleus (SCN) to light, possibly
      by modulating retinohypothalamic tract (RHT) input. In the present study, the
      anatomical distribution of the cognate receptor for BDNF, the TrkB tyrosine
      kinase, in RHT fibers and the SCN of rats was analyzed using combined
      immunohistochemical and anterograde tracing methods. Fluorescent immunostaining
      for the TrkB receptor was evident in fibers and cell bodies throughout the SCN.
      Dual labeling analysis revealed that there was substantial overlap in the
      distribution of TrkB immunostaining and cholera toxin subunit B (CTB)-labeling
      within RHT terminals and fibers projecting from the optic chiasm to the
      ventrolateral SCN. The present results suggest that RHT fibers may express TrkB
      receptors and thus provide a paracrine target for BDNF-mediated regulation of
      photic input to the SCN.

PMID- 15721223
TI  - Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in
      Alzheimer's disease brain.
AB  - The study is based on the premise that the enzyme lysyl oxidase (LO), which
      catalyzes the crosslinking of extracellular matrix (ECM) proteins, participates
      in ECM modulation and senile plaque formation in Alzheimer's disease (AD).
      Experiments on hippocampal samples indicate that LO activity is increased (about
      30%) in AD, but also in non-Alzheimer's dementia, as compared to controls with
      unrelated diseases. Immunohistochemistry with specific LO antibody indicates
      localization in blood vessel walls and in plaque-like structures. The number of
      LO-positive plaque-like structures in AD was over two-fold higher as compared to
      both non-Alzheimer's dementia and control groups. The findings lead us to suggest
      that active LO molecules in the ECM may be associated with plaque formation.

PMID- 15721222
TI  - ACE inhibition reduces activity of the plasminogen/plasmin and MMP systems in the
      brain of spontaneous hypertensive stroke-prone rats.
AB  - The spontaneously hypertensive stroke-prone rat (SHR-SP) is an experimental model
      of malignant hypertension which lead to secondary alterations of the
      extracellular matrix. Our aim was to determine ACE-inhibitor related changes of
      proteases involved in the reconstruction of the extracellular matrix in the
      brain. Twelve SHR-SP rats were randomized into two groups. Each group was treated
      with either an antihypertensive dose of ramipril or placebo for 6 months. Brain
      tissue plasminogen activator (t-PA) and urokinase (u-PA) were quantified by using
      casein-dependent plasminogen zymography, matrix metalloproteinase (MMP)-2 and MMP
      9, by MMP-zymography, and tissue inhibitor of MMP (TIMP)-1 and -2, by reverse
      zymography. The amounts of u-PA, t-PA, and MMPs were significantly reduced in
      animals treated with ACE inhibitor. Plasminogen zymography showed a 39% reduction
      of u-PA in the basal ganglia (p < 0.0001); t-PA expression was reduced by 26% in
      the cortex and by 33% in the basal ganglia (p < 0.0001). MMP-2 expression was
      reduced by 15% in the cortex (p < 0.05) and by 10% in the basal ganglia (p <
      0.05); MMP-9 expression significantly decreased by 37% in the cortex and by 25%
      in the basal ganglia (p < 0.0001 each). No differences were observed in the
      amount of TIMP-1 or TIMP-2. These findings provide new insights into the
      biochemical mechanisms underlying extracellular matrix proliferation and its
      modulation by ACE inhibitors. Therapeutic alterations that influence the
      proteolytic systems might prove important in the prevention of extracellular
      matrix accumulation and secondary microvascular vessel wall changes.

PMID- 15721224
TI  - Degradation of postural control system as a consequence of Parkinson's disease
      and ageing.
AB  - In this study we have shown how Parkinson's disease and ageing affect the
      postural control system. Our investigation of that system has involved analysis
      of quiet-standing center of pressure (COP) trajectories. Using the method derived
      from Langevin equation, we have found disease-specific and age-specific changes
      in the dynamics of the COP. These findings were obtained from a comparison of the
      diffusion matrix, the friction coefficient and the matrix of the fluctuation
      strength for healthy young, healthy elderly and parkinsonian (elderly) subjects
      under eyes-open and eyes-closed conditions. Especially the analysis of the
      friction coefficient and the matrix of the fluctuation strength have allowed the
      more detailed study of the postural control system of the parkinsonian and
      elderly subjects. We have found that the healthy elderly as well as parkinsonian
      subjects exhibit larger level of the muscular stochastic activity, compared to
      the young subjects. Furthermore, closure their eyes causes further increment of
      that activity. We have also shown that for the healthy elderly subjects a
      compensating mechanism, which can be described by the friction coefficient, acts
      under eyes-closed conditions, whereas for parkinsonian subjects this mechanism
      was not observed. Thus, the increase of the muscular activity is an age-specific
      indicator, whereas the absence of the compensation of that increase is a disease
      specific indicator.

PMID- 15721226
TI  - Modelling liver tissue properties using a non-linear visco-elastic model for
      surgery simulation.
AB  - In this work, we introduce an extension of the linear elastic tensor-mass method
      allowing fast computation of non-linear and visco-elastic mechanical forces and
      deformations for the simulation of biological soft tissue. We aim at developing a
      simulation tool for the planning of cryogenic surgical treatment of liver cancer.
      Percutaneous surgery simulation requires accurate modelling of the mechanical
      behaviour of soft tissue, and previous experimental characterizations have shown
      that linear elasticity is only a coarse approximation of the real properties of
      biological tissues. We first show that our model can simulate different types of
      non-linear and visco-elastic mechanical behaviours at speeds which are compatible
      with real-time applications. Then an experimental setup is presented which was
      used to characterize the mechanical properties of deer liver tissue under
      perforation by a biopsy needle. Experimental results demonstrate that a linear
      model is not suitable for simulating this application, while the proposed model
      succeeds in accurately modelling the axial load measured on the needle.

PMID- 15721227
TI  - Removing tetrahedra from manifold tetrahedralisation: application to real-time
      surgical simulation.
AB  - This paper proposes an efficient method for removing tetrahedra from a
      tetrahedral mesh while keeping its manifold property. We first define precisely
      the notion of manifold tetrahedral mesh and stress its relevance in the context
      of real-time surgery simulation. We then provide a method for removing a
      tetrahedron that complies with the manifold definition. This removal may require
      in some cases the removal of neighboring tetrahedra. After providing an
      exhaustive description of the tetrahedron removal algorithm, its efficiency is
      evaluated for different mesh configurations. This algorithm is currently used in
      the context of real-time surgery simulation where the action of an ultrasonic
      lancet can be simulated by the removal of small set of tetrahedra from a
      tetrahedralisation.

PMID- 15721228
TI  - A layered model of a virtual human intestine for surgery simulation.
AB  - In this paper, we propose a new approach to simulate the small intestine in a
      context of laparoscopic surgery. The ultimate aim of this work is to simulate the
      training of a basic surgical gesture in real-time: moving aside the intestine to
      reach hidden areas of the abdomen. The main problem posed by this kind of
      simulation is animating the intestine. The problem comes from the nature of the
      intestine: a very long tube which is not isotropically elastic, and is contained
      in a volume that is small when compared to the intestine's length. It coils
      extensively and collides with itself in many places. To do this, we use a layered
      model to animate the intestine. The intestine's axis is animated as a linear
      mechanical component. A specific sphere-based model handles contacts and self
      collisions. A skinning model is used to create the intestine's volume around the
      axis. This paper discusses and compares three different representations for
      skinning the intestine: a parametric surface model and two implicit surface
      models. The first implicit surface model uses point skeletons while the second
      uses local convolution surfaces. Using these models, we obtained good-looking
      results in real-time. Some videos of this work can be found in the online version
      at doi: 10.1016/j.media.2004.11.006 and at www
      imagis.imag.fr/Publications/2004/FLAMCFC04.

PMID- 15721229
TI  - From arteriographies to computational flow in saccular aneurisms: the INRIA
      experience.
AB  - Saccular aneurisms illustrate usefulness and possible techniques of image-based
      modeling of flow in diseased vessels. Aneurism flow is investigated in order to
      estimate the rupture risk, assuming that the pressure is the major factor and
      that high-pressure zones are correlated to within-wall strong-stress
      concentrations. Computational flow is also aimed at providing additional
      arguments for the treatment strategy. Angiographies of aneurismal vessels of
      large and medium size are processed to provide three-dimensional reconstruction
      of the vessel region of interest. Different reconstruction techniques are used
      for a side and a terminal aneurisms. Reconstruction techniques may lead to
      different geometries especially with poor input data. The associated facetisation
      is improved to get a computation-adapted surface triangulation, after a treatment
      of vessel ends and mesh adaptation. Once the volumic mesh is obtained, the
      pulsatile flow of an incompressible Newtonian blood is computed using in vivo non
      invasive flowmetry and the finite element method. High pressure zones are
      observed in the aneurism cavity. The pressure magnitude in the aneurism, the
      location and the size of high pressure zones depend mainly on the aneurism
      implantation on the vessel wall and its orientation with respect to the blood
      flux in the upstream vessel. The stronger the blood impacts on the aneurismal
      wall the higher the pressure. The state of the aneurism neck, where a high
      pressure zone can occur, and the location of the aneurism, with an easy access or
      not, give arguments for the choice between coiling and surgical clipping. Mesh
      size and 3D reconstruction procedure affect the numerical results. Helpful
      qualitative data are provided rather than accurate quantitative results in the
      context of multimodeling.

PMID- 15721230
TI  - Capturing intraoperative deformations: research experience at Brigham and Women's
      Hospital.
AB  - During neurosurgical procedures the objective of the neurosurgeon is to achieve
      the resection of as much diseased tissue as possible while achieving the
      preservation of healthy brain tissue. The restricted capacity of the conventional
      operating room to enable the surgeon to visualize critical healthy brain
      structures and tumor margin has lead, over the past decade, to the development of
      sophisticated intraoperative imaging techniques to enhance visualization.
      However, both rigid motion due to patient placement and nonrigid deformations
      occurring as a consequence of the surgical intervention disrupt the
      correspondence between preoperative data used to plan surgery and the
      intraoperative configuration of the patient's brain. Similar challenges are faced
      in other interventional therapies, such as in cryoablation of the liver, or
      biopsy of the prostate. We have developed algorithms to model the motion of key
      anatomical structures and system implementations that enable us to estimate the
      deformation of the critical anatomy from sequences of volumetric images and to
      prepare updated fused visualizations of preoperative and intraoperative images at
      a rate compatible with surgical decision making. This paper reviews the
      experience at Brigham and Women's Hospital through the process of developing and
      applying novel algorithms for capturing intraoperative deformations in support of
      image guided therapy.

PMID- 15721231
TI  - Tissue deformation and shape models in image-guided interventions: a discussion
      paper.
AB  - This paper promotes the concept of active models in image-guided interventions.
      We outline the limitations of the rigid body assumption in image-guided
      interventions and describe how intraoperative imaging provides a rich source of
      information on spatial location of anatomical structures and therapy devices,
      allowing a preoperative plan to be updated during an intervention. Soft tissue
      deformation and variation from an atlas to a particular individual can both be
      determined using non-rigid registration. Established methods using free-form
      deformations have a very large number of degrees of freedom. Three examples of
      deformable models--motion models, biomechanical models and statistical shape
      models--are used to illustrate how prior information can be used to restrict the
      number of degrees of freedom of the registration algorithm and thus provide
      active models for image-guided interventions. We provide preliminary results from
      applications for each type of model.

PMID- 15721232
TI  - Without DJ-1, the D2 receptor doesn't play.
AB  - Dopamine is an essential neuromodulator of the central nervous system whose
      activity is mediated through interaction with membrane receptors. Among these,
      the D2 receptor plays a pivotal role in regulating postsynaptic functions as well
      as dopamine synthesis and release from dopaminergic neurons. Parkinson's disease
      and parkinsonism are neurodegenerative diseases of dopaminergic neurons affecting
      the human brain. These diseases are clinically defined by a decrease in dopamine
      levels that manifest as motor impairements. In this issue of Neuron, Goldberg et
      al. report of an exciting link between the loss of function of DJ-1, a protein
      associated with familial parkinsonism, and D2 receptor activity.

PMID- 15721233
TI  - The ins and outs of intracellular chloride in olfactory receptor neurons.
AB  - Stimulation of olfactory receptor neurons with odors culminates in opening of a
      ciliary Ca2+-activated Cl- channel. Because intracellular Cl- ([Cl-]i) is above
      electrochemical equilibrium in these cells, the result is cell depolarization
      that triggers action potentials that carry information to the olfactory bulb. In
      this issue of Neuron, Reisert and coworkers use combined pharmacological and
      mouse genetic approaches to show that the transporter responsible for maintaining
      Cl- above electrochemical equilibrium is NKCC1, a (Na+)(2Cl-)(K+) cotransporter
      found in other tissues, including neurons.

PMID- 15721234
TI  - Minis: whence and wherefore?
AB  - In this issue of Neuron, Sara et al. find that spontaneously released miniature
      synaptic potentials arise from a pool of vesicles distinct from those released by
      neural activity. This modification of a basic tenet of the quantal hypothesis has
      important implications for the analysis of changes in synaptic transmission.

PMID- 15721235
TI  - Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the
      familial Parkinsonism-linked gene DJ-1.
AB  - The manifestations of Parkinson's disease are caused by reduced dopaminergic
      innervation of the striatum. Loss-of-function mutations in the DJ-1 gene cause
      early-onset familial parkinsonism. To investigate a possible role for DJ-1 in the
      dopaminergic system, we generated a mouse model bearing a germline disruption of
      DJ-1. Although DJ-1(-/-) mice had normal numbers of dopaminergic neurons in the
      substantia nigra, evoked dopamine overflow in the striatum was markedly reduced,
      primarily as a result of increased reuptake. Nigral neurons lacking DJ-1 were
      less sensitive to the inhibitory effects of D2 autoreceptor stimulation.
      Corticostriatal long-term potentiation was normal in medium spiny neurons of DJ
      1(-/-) mice, but long-term depression (LTD) was absent. The LTD deficit was
      reversed by treatment with D2 but not D1 receptor agonists. Furthermore, DJ-1(-/
      ) mice displayed hypoactivity in the open field. Collectively, our findings
      suggest an essential role for DJ-1 in dopaminergic physiology and D2 receptor
      mediated functions.

PMID- 15721236
TI  - Gene dosage effect on gamma-secretase component Aph-1b in a rat model for
      neurodevelopmental disorders.
AB  - A combination of genetic factors and early life events is thought to determine
      the vulnerability of an individual to develop a complex neurodevelopmental
      disorder like schizophrenia. Pharmacogenetically selected, apomorphine
      susceptible Wistar rats (APO-SUS) display a number of behavioral and
      pathophysiological features reminiscent of such disorders. Here, we report
      microarray analyses revealing in APO-SUS rats, relative to their counterpart APO
      UNSUS rats, a reduced expression of Aph-1b, a component of the gamma-secretase
      enzyme complex that is involved in multiple (neuro)developmental signaling
      pathways. The reduced expression is due to a duplicon-based genomic rearrangement
      event resulting in an Aph-1b dosage imbalance. The expression levels of the other
      gamma-secretase components were not affected. However, gamma-secretase cleavage
      activity was significantly changed, and the APO-SUS/-UNSUS Aph-1b genotypes
      segregated with a number of behavioral phenotypes. Thus, a subtle imbalance in
      the expression of a single, developmentally important protein may be sufficient
      to cause a complex phenotype.

PMID- 15721237
TI  - Coordinated motor neuron axon growth and neuromuscular synaptogenesis are
      promoted by CPG15 in vivo.
AB  - We have used in vivo time-lapse two-photon imaging of single motor neuron axons
      labeled with GFP combined with labeling of presynaptic vesicle clusters and
      postsynaptic acetylcholine receptors in Xenopus laevis tadpoles to determine the
      dynamic rearrangement of individual axon branches and synaptogenesis during motor
      axon arbor development. Control GFP-labeled axons are highly dynamic during the
      period when axon arbors are elaborating. Axon branches emerge from sites of
      synaptic vesicle clusters. These data indicate that motor neuron axon elaboration
      and synaptogenesis are concurrent and iterative. We tested the role of Candidate
      Plasticity Gene 15 (CPG15, also known as Neuritin), an activity-regulated gene
      that is expressed in the developing motor neurons in this process. CPG15
      expression enhances the development of motor neuron axon arbors by promoting
      neuromuscular synaptogenesis and by increasing the addition of new axon branches.

PMID- 15721238
TI  - Differential requirement for Plexin-A3 and -A4 in mediating responses of sensory
      and sympathetic neurons to distinct class 3 Semaphorins.
AB  - The class 3 Semaphorins Sema3A and Sema3F are potent axonal repellents that cause
      repulsion by binding Neuropilin-1 and Neuropilin-2, respectively. Plexins are
      implicated as signaling coreceptors for the Neuropilins, but the identity of the
      Plexins that transduce Sema3A and Sema3F responses in vivo is uncertain. Here, we
      show that Plexin-A3 and -A4 are key determinants of these responses, through
      analysis of a Plexin-A3/Plexin-A4 double mutant mouse. Sensory and sympathetic
      neurons from the double mutant are insensitive to Sema3A and Sema3F in vitro, and
      defects in axonal projections in vivo correspond to those seen in Neuropilin-1
      and -2 mutants. Interestingly, we found a differential requirement for these two
      Plexins: signaling via Neuropilin-1 is mediated principally by Plexin-A4, whereas
      signaling via Neuropilin-2 is mediated principally by Plexin-A3. Thus, Plexin-A3
      and -A4 contribute to the specificity of axonal responses to class 3 Semaphorins.

PMID- 15721239
TI  - The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent
      development of dendritic arbors and spines.
AB  - NMDA-type glutamate receptors play a critical role in the activity-dependent
      development and structural remodeling of dendritic arbors and spines. However,
      the molecular mechanisms that link NMDA receptor activation to changes in
      dendritic morphology remain unclear. We report that the Rac1-GEF Tiam1 is present
      in dendrites and spines and is required for their development. Tiam1 interacts
      with the NMDA receptor and is phosphorylated in a calcium-dependent manner in
      response to NMDA receptor stimulation. Blockade of Tiam1 function with RNAi and
      dominant interfering mutants of Tiam1 suggests that Tiam1 mediates effects of the
      NMDA receptor on dendritic development by inducing Rac1-dependent actin
      remodeling and protein synthesis. Taken together, these findings define a
      molecular mechanism by which NMDA receptor signaling controls the growth and
      morphology of dendritic arbors and spines.

PMID- 15721240
TI  - Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular
      mechanisms underlying kainate receptor selectivity.
AB  - Little is known about the molecular mechanisms underlying differences in the
      ligand binding properties of AMPA, kainate, and NMDA subtype glutamate receptors.
      Crystal structures of the GluR5 and GluR6 kainate receptor ligand binding cores
      in complexes with glutamate, 2S,4R-4-methylglutamate, kainate, and quisqualate
      have now been solved. The structures reveal that the ligand binding cavities are
      40% (GluR5) and 16% (GluR6) larger than for GluR2. The binding of AMPA- and GluR5
      selective agonists to GluR6 is prevented by steric occlusion, which also
      interferes with the high-affinity binding of 2S,4R-4-methylglutamate to AMPA
      receptors. Strikingly, the extent of domain closure produced by the GluR6 partial
      agonist kainate is only 3 degrees less than for glutamate and 11 degrees greater
      than for the GluR2 kainate complex. This, together with extensive interdomain
      contacts between domains 1 and 2 of GluR5 and GluR6, absent from AMPA receptors,
      likely contributes to the high stability of GluR5 and GluR6 kainate complexes.

PMID- 15721242
TI  - An isolated pool of vesicles recycles at rest and drives spontaneous
      neurotransmission.
AB  - Spontaneous synaptic vesicle fusion is a common property of all synapses. To
      trace the origin of spontaneously fused vesicles in hippocampal synapses, we
      tagged vesicles with fluorescent styryl dyes, antibodies against synaptotagmin-1,
      or horseradish peroxidase. We could show that synaptic vesicles recycle at rest,
      and after spontaneous exo-endocytosis, they populate a reluctantly releasable
      pool of limited size. Interestingly, vesicles in this spontaneously labeled pool
      were more likely to re-fuse spontaneously compared to vesicles labeled with
      activity. We found that blocking vesicle refilling at rest selectively depleted
      neurotransmitter from spontaneously fusing vesicles without significantly
      altering evoked transmission. Furthermore, in the absence of the vesicle SNARE
      protein synaptobrevin (VAMP), activity-dependent and spontaneously recycling
      vesicles could mix, suggesting a role for synaptobrevin in the separation of the
      two pools. Taken together these results suggest that spontaneously recycling
      vesicles and activity-dependent recycling vesicles originate from distinct pools
      with limited cross-talk with each other.

PMID- 15721243
TI  - The mechanism of intrinsic amplification of hyperpolarizations and spontaneous
      bursting in striatal cholinergic interneurons.
AB  - Striatal cholinergic interneurons pause their ongoing firing in response to
      sensory stimuli that have acquired meaning as a signal for learned behavior. In
      slices, these cells exhibit both spontaneous activity patterns and spontaneous
      pauses very similar to those seen in vivo. The mechanisms responsible for ongoing
      firing and spontaneous pauses were studied in striatal slices using perforated
      patch recordings. All hyperpolarizations, whether spontaneous or generated by
      current injection, were amplified and shaped by two hyperpolarization-activated
      currents. Hyperpolarization onsets were regeneratively amplified by a potassium
      current (KIR) whose activation promoted further hyperpolarization. The
      termination of hyperpolarizations was controlled by a time-dependent nonspecific
      cation current (HCN). The duration and even the sizes of spontaneous and driven
      hyperpolarizations and pauses in spontaneous activity in cholinergic interneurons
      are largely autonomous properties of the neuron, rather than reflections of
      characteristics of the input eliciting the response.

PMID- 15721244
TI  - Nucleus accumbens neurons are innately tuned for rewarding and aversive taste
      stimuli, encode their predictors, and are linked to motor output.
AB  - The nucleus accumbens (NAc) is a key component of the brain's reward pathway, yet
      little is known of how NAc cells respond to primary rewarding or aversive
      stimuli. Here, naive rats received brief intraoral infusions of sucrose and
      quinine paired with cues in a classical conditioning paradigm while the
      electrophysiological activity of individual NAc neurons was recorded. NAc neurons
      (102) were typically inhibited by sucrose (39 of 52, 75%) or excited by quinine
      (30 of 40, 75%) infusions. Changes in firing rate were correlated with the
      oromotor response to intraoral infusions. Most taste-responsive neurons responded
      to only one of the stimuli. NAc neurons developed responses to the cues paired
      with sucrose and quinine. Thus, NAc neurons are innately tuned to rewarding and
      aversive stimuli and rapidly develop responses to predictive cues. The results
      indicate that the output of the NAc is very different when rats taste rewarding
      versus aversive stimuli.

PMID- 15721241
TI  - Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons.
AB  - In vertebrate olfactory receptor neurons (ORNs), the odorant-triggered receptor
      current flows through two distinct ion channels on the sensory cilia: Ca2+ influx
      through a cyclic nucleotide-gated (CNG) channel followed by Cl- efflux through a
      Ca2+-activated anion channel. The excitatory Cl- current amplifies the small CNG
      current and crucially depends on a high intracellular Cl- concentration. We show
      here that a (Na+)-(K+)-(2Cl-) cotransporter, NKCC1, is required for this Cl-
      current, in that ORNs deficient in Nkcc1 or incubated with an NKCC blocker
      (bumetanide) lack the Cl- current. Surprisingly, immunocytochemistry indicates
      that NKCC1 is located on the somata and dendrites of ORNs rather than the cilia,
      where transduction occurs. This topography is remarkably similar to the situation
      in secretory epithelial cells, where basolateral Cl- uptake and apical Cl- efflux
      facilitate transepithelial fluid movement. Thus, a single functional architecture
      serves two entirely different purposes, probably underscoring the epithelial
      origin of the ORNs.

PMID- 15721245
TI  - Cascade models of synaptically stored memories.
AB  - Storing memories of ongoing, everyday experiences requires a high degree of
      plasticity, but retaining these memories demands protection against changes
      induced by further activity and experience. Models in which memories are stored
      through switch-like transitions in synaptic efficacy are good at storing but bad
      at retaining memories if these transitions are likely, and they are poor at
      storage but good at retention if they are unlikely. We construct and study a
      model in which each synapse has a cascade of states with different levels of
      plasticity, connected by metaplastic transitions. This cascade model combines
      high levels of memory storage with long retention times and significantly
      outperforms alternative models. As a result, we suggest that memory storage
      requires synapses with multiple states exhibiting dynamics over a wide range of
      timescales, and we suggest experimental tests of this hypothesis.

PMID- 15721246
TI  - Adaptation of oriented and unoriented color-selective neurons in human visual
      areas.
AB  - Primary visual cortex contains at least two distinct populations of color
      selective cells: neurons in one have circularly symmetric receptive fields and
      respond best to reddish and greenish light, while neurons in another have
      oriented receptive fields and a variety of color preferences. The relative
      prevalence and perceptual roles of the two kinds of neurons remain controversial,
      however. We used fMRI and a selective adaptation technique to measure responses
      attributable to these two populations. The technique revealed evidence of
      adaptation in both populations and indicated that they each produced strong
      signals in V1 and other human visual areas. The activity of both sets of neurons
      was also reflected in color appearance measurements made with the same stimuli.
      Thus, both oriented and unoriented color-selective cells in V1 are important
      components of the neural pathways that underlie perception of color.

PMID- 15721248
TI  - Planetary systems biology.
AB  - Combining paleogenetics, protein engineering, synthetic biology, and metabolic
      modeling, a planetary biology perspective is brought to bear on adaptive
      evolutionary events in ancient bacteria.

PMID- 15721247
TI  - Activation in posterior superior temporal sulcus parallels parameter inducing the
      percept of animacy.
AB  - An essential, evolutionarily stable feature of brain function is the detection of
      animate entities, and one of the main cues to identify them is their movement. We
      developed a model of a simple interaction between two objects, in which an
      increase of the correlation between their movements varied the amount of
      interactivity and animacy observers attributed to them. Functional magnetic
      resonance imaging revealed that activation in the posterior superior temporal
      sulcus and gyrus (pSTS/pSTG) increased in relation to the degree of correlated
      motion between the two objects. This activation increase was not different when
      subjects performed an explicit or implicit task while observing these interacting
      objects. These data suggest that the pSTS and pSTG play a role in the automatic
      identification of animate entities, by responding directly to an objective
      movement characteristic inducing the percept of animacy, such as the amount of
      interactivity between two moving objects.

PMID- 15721249
TI  - OS-9: another piece in the HIF complex story.
AB  - In this issue of Molecular Cell, the Semenza group reports that OS-9, a common
      protein of unassigned function, promotes the O2-dependent degradation of hypoxia
      inducible factor (HIF) via binding to both HIF and the HIF prolyl-hydroxylases,
      implying that OS-9 is part of a multiprotein complex involved in the hypoxic
      response (Baek et al., 2005).

PMID- 15721250
TI  - E1 on the move.
AB  - E1 enzymes activate ubiquitin or related proteins and pass them to E2 enzymes. A
      recent structure and associated biochemical studies (Huang et al., 2005) show how
      an E1 binds its cognate E2 and indicates that large, conformational changes will
      be an integral component of the E1 reaction cycle.

PMID- 15721251
TI  - Spiraled origins.
AB  - Recent studies have established that the eukaryotic actin-based cytoskeleton has
      prokaryotic origins. In addition to regulating cell shape and polarity, Gitai et
      al. (2005) provide convincing evidence that the Caulobacter actin homolog MreB
      also mediates the early segregation of the chromosomal origin, a typical
      functional role of the eukaryotic tubulin-based cytoskeleton.

PMID- 15721252
TI  - HIV-1-associated uracil DNA glycosylase activity controls dUTP misincorporation
      in viral DNA and is essential to the HIV-1 life cycle.
AB  - Uracilation of DNA represents a constant threat to the survival of many organisms
      including viruses. Uracil may appear in DNA either by cytosine deamination or by
      misincorporation of dUTP. The HIV-1-encoded Vif protein controls cytosine
      deamination by preventing the incorporation of host-derived APOBEC3G cytidine
      deaminase into viral particles. Here, we show that the host-derived uracil DNA
      glycosylase UNG2 enzyme, which is recruited into viral particles by the HIV-1
      encoded integrase domain, is essential to the viral life cycle. We demonstrate
      that virion-associated UNG2 catalytic activity can be replaced by the packaging
      of heterologous dUTPase into virion, indicating that UNG2 acts to counteract dUTP
      misincorporation in the viral genome. Therefore, HIV-1 prevents incorporation of
      dUTP in viral cDNA by UNG2-mediated uracil excision followed by a dNTP-dependent,
      reverse transcriptase-mediated endonucleolytic cleavage and finally by strand
      displacement polymerization. Our findings indicate that pharmacologic strategies
      aimed toward blocking UNG2 packaging should be explored as potential HIV/AIDS
      therapeutics.

PMID- 15721253
TI  - Crystallographic identification and functional characterization of phospholipids
      as ligands for the orphan nuclear receptor steroidogenic factor-1.
AB  - The orphan nuclear receptor steroidogenic factor 1 (SF-1) regulates the
      differentiation and function of endocrine glands. Although SF-1 is constitutively
      active in cell-based assays, it is not known whether this transcriptional
      activity is modulated by ligands. Here, we describe the 1.5 angstroms crystal
      structure of the SF-1 ligand binding domain in complex with an LXXLL motif from a
      coregulator protein. The structure reveals the presence of a phospholipid ligand
      in a surprisingly large pocket (approximately 1600 angstroms3), with the receptor
      adopting the canonical active conformation. The bound phospholipid is readily
      exchanged and modulates SF-1 interactions with coactivators. Mutations designed
      to reduce the size of the SF-1 pocket or to disrupt hydrogen bonds with the
      phospholipid abolish SF-1/coactivator interactions and significantly reduce SF-1
      transcriptional activity. These findings provide evidence that SF-1 is regulated
      by endogenous ligands and suggest an unexpected relationship between
      phospholipids and endocrine development and function.

PMID- 15721254
TI  - OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to
      promote oxygen-dependent degradation of HIF-1alpha.
AB  - Hypoxia-inducible factor 1 (HIF-1) functions as a master regulator of oxygen
      homeostasis in metazoan species. HIF-1 mediates changes in gene transcription in
      response to changes in cellular oxygenation. The half-life of the HIF-1alpha
      subunit is determined by oxygen-dependent prolyl hydroxylation, which is required
      for binding of the von Hippel-Lindau protein (VHL), the recognition component of
      an E3 ubiquitin ligase that targets HIF-1alpha for ubiquitination and
      degradation. Here, we demonstrate that OS-9, the protein product of a widely
      expressed gene, interacts with both HIF-1alpha and HIF-1alpha prolyl
      hydroxylases. OS-9 gain-of-function promotes HIF-1alpha hydroxylation, VHL
      binding, proteasomal degradation of HIF-1alpha, and inhibition of HIF-1-mediated
      transcription. OS-9 loss-of-function caused by RNA interference increases HIF
      1alpha protein levels, HIF-1-mediated transcription, and VEGF mRNA expression
      under nonhypoxic conditions. These data indicate that OS-9 is an essential
      component of a multiprotein complex that regulates HIF-1alpha levels in an O2
      dependent manner.

PMID- 15721255
TI  - Structure of an ultraweak protein-protein complex and its crucial role in
      regulation of cell morphology and motility.
AB  - Weak protein-protein interactions (PPIs) (K(D) > 10(-6) M) are critical
      determinants of many biological processes. However, in contrast to a large
      growing number of well-characterized, strong PPIs, the weak PPIs, especially
      those with K(D) > 10(-4) M, are poorly explored. Genome wide, there exist few 3D
      structures of weak PPIs with K(D) > 10(-4) M, and none with K(D) > 10(-3) M.
      Here, we report the NMR structure of an extremely weak focal adhesion complex
      (K(D) approximately 3 x 10(-3) M) between Nck-2 SH3 domain and PINCH-1 LIM4
      domain. The structure exhibits a remarkably small and polar interface with
      distinct binding modes for both SH3 and LIM domains. Such an interface suggests a
      transient Nck-2/PINCH-1 association process that may trigger rapid focal adhesion
      turnover during integrin signaling. Genetic rescue experiments demonstrate that
      this interface is indeed involved in mediating cell shape change and migration.
      Together, the data provide a molecular basis for an ultraweak PPI in regulating
      focal adhesion dynamics during integrin signaling.

PMID- 15721257
TI  - SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway.
AB  - In metazoa, regulation of the phosphorylation state of UPF1 is crucial for
      nonsense-mediated mRNA decay (NMD), a process by which aberrant mRNAs containing
      nonsense mutations are degraded. UPF1 is targeted for dephosphorylation by three
      related proteins, SMG5, SMG6, and SMG7. We report here the crystal structure of
      the N-terminal domain of SMG7. The structure reveals that SMG7 contains a 14-3-3
      like domain. Residues that bind phosphoserine-containing peptides in 14-3-3 are
      conserved at the equivalent positions in SMG7. Mutation of these residues impairs
      UPF1 binding to SMG7 in vitro and UPF1 recruitment to cytoplasmic mRNA decay foci
      in vivo, suggesting that SMG7 acts as an adaptor in targeting mRNAs associated
      with phosphorylated UPF1 for degradation. The 14-3-3 site of SMG7 is conserved in
      SMG5 and SMG6. These data also imply that the homologous human Est1 might have a
      14-3-3 function at telomeres, and that phosphorylation events may be important
      for telomerase regulation.

PMID- 15721256
TI  - BH3 domains of BH3-only proteins differentially regulate Bax-mediated
      mitochondrial membrane permeabilization both directly and indirectly.
AB  - Using a Bax-dependent membrane-permeabilization assay, we show that peptides
      corresponding to the BH3 domains of Bcl-2 family "BH3-only" proteins have dual
      functions. Several BH3 peptides relieved the inhibition of Bax caused by the
      antiapoptotic Bcl-x(L) and/or Mcl-1 proteins, some displaying a specificity for
      either Bcl-x(L) or Mcl-1. Besides having this derepression function, the Bid and
      Bim peptides activated Bax directly and were the only BH3 peptides tested that
      could potently induce cytochrome c release from mitochondria in cultured cells.
      Furthermore, Bax activator molecules (cleaved Bid protein and the Bim BH3
      peptide) synergistically induced cytochrome c release when introduced into cells
      along with derepressor BH3 peptides. These observations support a unified model
      of BH3 domain function, encompassing both positive and negative regulation of
      other Bcl-2 family members. In this model, the simple inhibition of antiapoptotic
      functions is insufficient to induce apoptosis unless a direct activator of Bax or
      Bak is present.

PMID- 15721258
TI  - A bacterial G protein-mediated response to replication arrest.
AB  - To define factors in E. coli promoting survival to replication fork stress, we
      isolated insertion mutants sensitive to replication inhibitors. One insertion
      caused partial loss of the universally conserved GTPase, obgE/yhbZ gene. Although
      obgE is essential for growth, our insertion allele supported viability until
      challenged with various replication inhibitors. A mutation designed to negate the
      GTPase activity of the protein produced similar phenotypes, but was genetically
      dominant. Synergistic genetic interactions with recA and recB suggested that
      chromosome breaks and regressed forks accumulate in obgE mutants. Mutants in obgE
      also exhibited asynchronous overreplication during normal growth, as revealed by
      flow cytometry. ObgE overexpression caused SeqA foci, normally localized to
      replication forks, to spread extensively within the cell. We propose that ObgE
      defines a pathway analogous to the replication checkpoint response of eukaryotes
      and acts in a complementary way to the RecA-dependent SOS response to promote
      bacterial cell survival to replication fork arrest.

PMID- 15721259
TI  - DNA polymerase V and RecA protein, a minimal mutasome.
AB  - A hallmark of the Escherichia coli SOS response is the large increase in
      mutations caused by translesion synthesis (TLS). TLS requires DNA polymerase V
      (UmuD'2C) and RecA. Here, we show that pol V and RecA interact by two distinct
      mechanisms. First, pol V binds to RecA in the absence of DNA and ATP and second,
      through its UmuD' subunit, requiring DNA and ATP without ATP hydrolysis. TLS
      occurs in the absence of a RecA nucleoprotein filament but is inhibited in its
      presence. Therefore, a RecA nucleoprotein filament is unlikely to be required for
      SOS mutagenesis. Pol V activity is severely diminished in the absence of RecA or
      in the presence of RecA1730, a mutant defective for pol V mutagenesis in vivo.
      Pol V activity is strongly enhanced with RecA mutants constitutive for
      mutagenesis in vivo, suggesting that RecA is an obligate accessory factor that
      activates pol V for SOS mutagenesis.

PMID- 15721260
TI  - Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly
      of telomere replication proteins in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, telomere replication occurs in late S phase and is
      accompanied by dynamic remodeling of its protein components. Here, we show that
      MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in
      DNA double-strand break (DSB) repair, is recruited to the telomeres in late S
      phase. MRX is required for the late S phase-specific recruitment of ATR-like
      kinase Mec1 to the telomeres. Mec1, in turn, contributes to the assembly of the
      telomerase regulators Cdc13 and Est1 at the telomere ends. Our results provide a
      model for the hierarchical assembly of telomere-replication proteins in late S
      phase; this involves triggering by the loading of MRX onto the chromosome
      termini. The recruitment of DNA repair-related proteins to the telomeres at
      particular times in the cell cycle suggests that the normal terminus of a
      chromosome is recognized as a DSB during the course of replication.

PMID- 15721261
TI  - Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere
      proximal Sir2 association and gene silencing.
AB  - Low levels of histone covalent modifications are associated with gene silencing
      at telomeres and other regions in the yeast S. cerevisiae. Although the histone
      deacetylase Sir2 maintains low acetylation, mechanisms responsible for low H2B
      ubiquitylation and low H3 methylation are unknown. Here, we show that the
      ubiquitin protease Ubp10 targets H2B for deubiquitylation, helping to localize
      Sir2 to the telomere. Ubp10 exhibits reciprocal Sir2-dependent preferential
      localization proximal to telomeres, where Ubp10 serves to maintain low H2B Lys123
      ubiquitylation in this region and, through previously characterized crosstalk,
      maintains low H3 Lys4 and Lys79 methylation in a slightly broader region. Ubp10
      is also localized to the rDNA locus, a second silenced domain, where it similarly
      maintains low histone methylation. We compare Ubp10 to Ubp8, the SAGA-associated
      H2B deubiquitylase involved in gene activation, and show that telomeric and gene
      silencing functions are specific to Ubp10. Our results suggest that these H2B
      deubiquitylating enzymes have distinct genomic functions.

PMID- 15721262
TI  - Chemical activation of Sir2-dependent silencing by relief of nicotinamide
      inhibition.
AB  - Sir2 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase
      involved in gene silencing and longevity. Cellular stresses affect Sir2 activity,
      but the mechanisms of Sir2 regulation are debated. Nicotinamide has been proposed
      as a physiological regulator that inhibits Sir2 deacetylase activity by chemical
      reversal of a covalent reaction intermediate. We demonstrate a chemical strategy
      to activate Sir2-dependent transcriptional silencing and present evidence that
      the endogenous level of nicotinamide limits Sir2 activity in wild-type (wt) yeast
      cells. Nicotinamide inhibition of Sir2 is antagonized in vitro by
      isonicotinamide, which causes an increase in Sir2 deacetylation activity.
      Isonicotinamide also substantially increases transcriptional silencing at Sir2
      regulated loci in wt strains and in strains lacking key NAD+ salvage pathway
      enzymes (PNC1 and NPT1). Thus, a nicotinamide antagonist is a Sir2 agonist in
      vitro and in vivo.

PMID- 15721263
TI  - A flexible domain is essential for the large step size and processivity of myosin
      VI.
AB  - Myosin VI moves processively along actin with a larger step size than expected
      from the size of the motor. Here, we show that the proximal tail (the
      approximately 80-residue segment following the IQ domain) is not a rigid
      structure but, rather, a flexible domain that permits the heads to separate. With
      a GCN4 coiled coil inserted in the proximal tail, the heads are closer together
      in electron microscopy (EM) images, and the motor takes shorter processive steps.
      Single-headed myosin VI S1 constructs take nonprocessive 12 nm steps, suggesting
      that most of the processive step is covered by a diffusive search for an actin
      binding site. Based on these results, we present a mechanical model that
      describes stepping under an applied load.

PMID- 15721264
TI  - 1H NMR analysis as a diagnostic probe for human saliva.
AB  - The applications of high resolution (1)H NMR analysis as a diagnostic probe for
      human saliva are reviewed with special reference to diabetes mellitus, and a
      recently published report regarding the ability of this technique to detect
      advanced glycation endproducts (AGEs) in this biofluid [Biochem. Biophys. Res.
      Commun. 323 (2004) 377-381]. We also demonstrate that hypochlorous
      acid/hypochlorite (HOCl/OCl(-))-induced modifications to the (1)H NMR profiles of
      human salivary supernatants arise from the chlorination and, where appropriate,
      oxidation of amino acids and malodorous amines, together with the oxidation of
      carbohydrates and alpha-keto acid anions. The attack of HOCl/OCl(-) on
      carbohydrates yields formate (singlet, delta = 8.46 ppm), the (1)H NMR signal of
      which was erroneously assigned to AGE species by the authors of [Biochem.
      Biophys. Res. Commun. 323 (2004) 377-381].

PMID- 15721265
TI  - Suppression of the alpha-isoform of class II phosphoinositide 3-kinase gene
      expression leads to apoptotic cell death.
AB  - Phosphoinositide 3-kinases (PI3Ks) have known to be key enzymes activating
      intracellular signaling molecules when a number of growth factors bind to their
      cell surface receptors. PI3Ks are divided into three classes (I, II, and III) and
      enzymes of each class have different tissue-specificities and physiological
      functions. Class II PI3Ks consist of three isoforms (alpha,beta,gamma). Although
      the alpha-isoform (PI3K-C2alpha) is considered ubiquitous and preferentially
      activated by insulin rather than the beta-isoform, the physiological significance
      of PI3K-C2alpha is poorly understood. The present study aimed to determine
      whether PI3K-C2alpha is associated with the suppression of apoptotic cell death.
      Different sense- and antisense oligonucleotides (ODNs) were synthesized based on
      the sequence of C2 domain of PI3K-C2alpha gene. Transfection of CHO-IR cells with
      two different antisense ODNs clearly reduced the protein content as well as mRNA
      levels of PI3K-C2alpha whereas neither the nonspecific mock- nor sense ODNs
      affected. The decrease of PI3K-C2alpha gene expression was paralleled by cellular
      changes indicating apoptotic cell death such as nuclear condensation, formation
      of apoptotic bodies, and DNA fragmentation. PI3K-C2alpha mRNA levels were also
      reduced when cells were incubated in growth factor-deficient medium.
      Supplementing growth factors (serum or insulin) into medium lead to an increase
      of PI3K-C2alpha mRNA levels. This finding strongly suggests that PI3K-C2alpha is
      a crucial survival factor.

PMID- 15721266
TI  - Transcriptional profiling of human herpesvirus type B (HHV-6B) in an adult T cell
      leukemia cell line as in vitro model for persistent infection.
AB  - Human herpesvirus 6 (HHV-6), which is present in more than 90% of the human, is
      known to cause infectious diseases in immuno-compromised patients, e.g.,
      transplant patients. To clarify the possible role of the pattern of expression of
      HHV-6 genes in various types of HHV-6B infection, we sought to determine whether
      or not viral DNA microarray could be used for detailed characterization of viral
      transcription using a HHV-6B DNA microarray that contains 97 known open reading
      frames of HHV-6B. A subset of genes are preferentially expressed in persistent
      infection: U16 (IE-B, transactivator, US22 gene family), U18 (IE-B, homolog to
      HCMV IE glycoprotein), U20 (glycoprotein), U27 (DNA polymerase processivity
      transactivator), U82 (gL, gH accessory protein), U83 (chemokine), U85 (OX-2
      homology, glycoprotein), U90 (IE-A), and U94 (transactivator), respectively.
      Although the function of each HHV-6B is not fully understood, our study suggests
      that comprehensive analysis of HHV-6B transcription is useful not only to clarify
      the pathogenesis of the virus but also to develop new strategies for anti-viral
      drugs.

PMID- 15721267
TI  - Leptin induces hypertrophy via p38 mitogen-activated protein kinase in rat
      vascular smooth muscle cells.
AB  - The hypertrophy of vascular smooth muscle cells (VSMCs) is critical in vascular
      remodeling associated with hypertension, atherosclerosis, and restenosis.
      Recently, leptin has appeared to play a pivotal role in vascular remodeling.
      However, the mechanism by which leptin induces hypertrophy in vascular smooth
      muscle cells is still unknown. We studied the role of leptin as a potential
      hypertrophic factor in rat VSMCs. In the present study, leptin significantly
      increased [(3)H]leucine incorporation and the total protein/DNA ratio in VSMCs.
      The maximal hypertrophic effect was at 100ng/ml of leptin. Leptin induced
      phosphorylation and activation of p38 mitogen-activated protein (p38 MAP) kinase
      and of signal transducers and activators of transcription 3 in a concentration-
      and time-dependent manner. A p38 MAP kinase inhibitor SB203580 significantly
      inhibited leptin-induced hypertrophy, AG490 (a JAK2 inhibitor) partially
      inhibited it, and other MAP kinase inhibitors, PD98059 (an ERK inhibitor) and
      SP600125 (a JNK inhibitor), had no effect. These results indicate that leptin
      directly stimulates cellular hypertrophy via p38 MAP kinase in rat VSMCs.

PMID- 15721268
TI  - Human adipose stromal cells expanded in human serum promote engraftment of human
      peripheral blood hematopoietic stem cells in NOD/SCID mice.
AB  - Human mesenchymal stem cells (hMSC), that have been reported to be present in
      bone marrow, adipose tissues, dermis, muscles, and peripheral blood, have the
      potential to differentiate along different lineages including those forming bone,
      cartilage, fat, muscle, and neuron. Therefore, hMSC are attractive candidates for
      cell and gene therapy. The optimal conditions for hMSC expansion require medium
      supplemented with fetal bovine serum (FBS). Some forms of cell therapy will
      involve multiple doses, raising a concern over immunological reactions caused by
      medium-derived FBS proteins. In this study, we cultured human adipose stromal
      cells (hADSC) and bone marrow stroma cells (HBMSC) in human serum (HS) during
      their isolation and expansion, and demonstrated that they maintain their
      proliferative capacity and ability for multilineage differentiation and promote
      engraftment of peripheral blood-derived CD34(+) cells mobilized from bone marrow
      in NOD/SCID mice. Our results indicate that hADSC and hBMSC cultured in HS can be
      used for clinical trials of cell and gene therapies, including promotion of
      engraftment after allogeneic HSC transplantation.

PMID- 15721269
TI  - Identification of novel Nox4 splice variants with impact on ROS levels in A549
      cells.
AB  - NAD(P)H oxidases (Nox) generate reactive oxygen species (ROS) that function in
      host defense and cellular signaling. While analyzing the expression of Nox4 at
      the protein and the mRNA levels, we identified four novel Nox4 splice-variants
      Nox4B, Nox4C, Nox4D, and Nox4E, which are expressed in human lung A549 cell line
      and lung tissues. One Nox4 isoform lacks the first NAD(P)H binding site (Nox4B)
      while another lacks all FADH and NAD(P)H binding sites (Nox4C). Cells over
      expressing NoxB or Nox4C exhibited a decrease in ROS levels. Thus, these isoforms
      have dominant negative characteristics for ROS generation. Two other splice
      variants (Nox4D, Nox4E) lack the transmembrane domains, suggesting these as non
      membrane associated isoforms. Nox4D contains all FADH and NAD(P)H binding domains
      and shows the same rate of ROS generation as Nox4 prototype. Taken together, we
      suggest that Nox4 exists as several isoforms that may have different functions in
      ROS-related cell signaling.

PMID- 15721270
TI  - 3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor
      stimulated human colon cancer cell proliferation.
AB  - The novel cyclic dinucleotide, 3',5'-cyclic diguanylic acid, cGpGp (c-di-GMP), is
      a naturally occurring small molecule that regulates important signaling
      mechanisms in prokaryotes. Recently, we showed that c-di-GMP has "drug-like"
      properties and that c-di-GMP treatment might be a useful antimicrobial approach
      to attenuate the virulence and pathogenesis of Staphylococcus aureus and prevent
      or treat infection. In the present communication, we report that c-di-GMP (50
      microM) has striking properties regarding inhibition of cancer cell proliferation
      in vitro. c-di-GMP inhibits both basal and growth factor (acetylcholine and
      epidermal growth factor)-induced cell proliferation of human colon cancer (H508)
      cells. Toxicity studies revealed that exposure of normal rat kidney cells and
      human neuroblastoma cells to c-di-GMP at biologically relevant doses showed no
      lethal cytotoxicity. Cyclic dinucleotides, such as c-di-GMP, represent an
      attractive and novel "drug-platform technology" that can be used not only to
      develop new antimicrobial agents, but also to develop novel therapeutic agents to
      prevent or treat cancer.

PMID- 15721271
TI  - Selective cytotoxicity of ascochlorin in ER-negative human breast cancer cell
      lines.
AB  - While agents targeting estrogen receptors are most effective in adjuvant therapy
      for human breast cancers expressing estrogen receptors after surgery, breast
      cancers lacking estrogen receptor are clinically serious, because they are highly
      malignant and exhibit resistance to the usual anti-cancer drugs, including
      estrogen receptor-antagonists and DNA breaking agents. Here, we found that MX-1,
      a human breast cancer cell line lacking estrogen receptors, exhibited higher AP-1
      activity and expressed higher levels of c-Jun, c-Fos, and Fra-1 when compared
      with conventional estrogen receptor-positive human breast cancer cell lines. The
      prenylphenol antibiotic ascochlorin suppressed the AP-1 activity of MX-1 cells,
      and selectively killed MX-1 cells, partly due to induction of apoptosis. Our
      results suggest that AP-1 is an effective clinical target molecule for the
      treatment of estrogen receptor-negative human breast cancer.

PMID- 15721272
TI  - Quantitative mRNA expression profiling of heat-shock protein families in rainbow
      trout cells.
AB  - We isolated multiple HSPs from rainbow trout Oncorhynchus mykiss RTG-2 cells and
      quantitatively compared their mRNA levels between unstressed and heat-shocked
      cells using real-time RT-PCR analysis. Consequently, we isolated nine cDNAs
      encoding HSPs from heat-shocked RTG-2 cells, namely, Hsp90betaa, Hsp90betab,
      Grp78, Hsp70a, Hsc70a, Hsc70b, Cct8, Hsp47, and DnaJ homolog. Quantitative RT-PCR
      analyses, in which Hsp70b isolated previously was included, showed that the mRNA
      accumulation levels of Hsp70a, Hsp70b, Hsc70a, Hsc70b, and Hsp47 were
      significantly increased after heat shock, and the increased levels of two Hsp70s,
      Hsp70a, and Hsp70b, were most conspicuous. In the case of Hsc70s, the increased
      level of Hsc70b was more remarkable than that of Hsc70a. These results
      demonstrate the importance of a comprehensive expression analysis of HSPs for
      better understanding of the cellular stress response in fish, especially in
      tetraploid species such as rainbow trout.

PMID- 15721273
TI  - Cigarette smoke extract induces endothelial cell injury via JNK pathway.
AB  - Cigarette smoking is the most crucial factor responsible for chronic obstructive
      pulmonary disease (COPD). The precise mechanisms of the development of the
      disease have, however, not been fully understood. Recently, impairment of
      pulmonary endothelial cells has been increasingly recognized as a critical
      pathophysiological process in COPD. To verify this hypothesis, we examined how
      cigarette smoke extract (CSE) damages human umbilical vein endothelial cells
      (HUVECs). CSE activated c-Jun N-terminal kinase (JNK), and treatment of HUVECs
      with SP600125, a specific inhibitor of the JNK pathway, significantly suppressed
      endothelial cell damage by CSE. In contrast, inhibition of the extracellular
      regulated kinase or the p38 pathway did not affect the cytotoxicity of CSE.
      Furthermore, anti-oxidants superoxide dismutase and catalase reduced CSE-induced
      JNK phosphorylation and endothelial cell injury. These results indicate that CSE
      damages vascular endothelial cells through the JNK pathway activated, at least
      partially, by oxidative stress.

PMID- 15721274
TI  - Changes in adsorption and permeability of mitoxantrone on plasma membrane of
      BCRP/MXR resistant cells.
AB  - A selective analysis of adsorbed mitoxantrone (MTX) was performed by surface
      enhanced Raman scattering (SERS) at the range of cellular membrane. Disruption of
      the membrane fluidity was carried out to appraise changes in membrane adsorption
      of MTX and drug uptake in sensitive (HCT-116 S) and resistant BCRP/MXR (HCT-116
      R) cells. Based on spectral MTX modifications, micro-SERS spectroscopy
      discriminated clearly drug adsorption phenomena on plasma membrane from drug in
      solution. A 3-fold higher SERS intensity of MTX for HCT-116 R was observed
      concluding to a higher drug adsorption on resistant membrane. The increase of
      membrane fluidity with benzyl alcohol (BA) or chloroform (CF) resulted in a 3
      fold decrease of MTX adsorption on HCT-116 R, exclusively. BA and CF improved
      intracellular accumulation of MTX (e.g., 823 and 191 pmol MTX/10(6) HCT-116 R
      incubated with or without BA). At 4 degrees C, drug accumulation measurements
      showed a decrease of MTX permeability in resistant membrane (42 pmol MTX/10(6)
      cells), restored with fluidizers (e.g., 342 pmol MTX/10(6) cells with BA).
      Fluorescence confocal microscopy involved an exclusive MTX emission around the
      plasma membrane of resistant cells whereas fluidizers increased the intracellular
      uptake of MTX in both cell lines at the same time with less drug emission around
      the plasma membrane. Changes of the membrane structure of resistant cells should
      modify both drug adsorption and membrane permeation.

PMID- 15721275
TI  - Lysophosphatidylcholine induces tPA gene expression through CRE-dependent
      mechanism.
AB  - Lysophosphatidylcholine (lysoPC) is implicated in the development of
      atherosclerosis and certain autoimmune diseases, and is reported to induce tissue
      type plasminogen activator (tPA) at the protein level in endothelial cells. This
      study was designed to investigate the effect of lysoPC on tPA gene expression and
      the underlying molecular mechanisms in cultured endothelial cells. LysoPC
      transiently induced the mRNA expression of tPA in endothelial cells. LysoPC also
      induced the mRNA expression of urokinase-type plasminogen activator (uPA), uPA
      receptor, and plasminogen activator inhibitor-1, but the kinetics were different
      from that of tPA. Promoter analysis revealed that the cyclic AMP-responsive
      element of the tPA gene (tPACRE) is required for lysoPC-induced tPA expression.
      Furthermore, an electrophoresis mobility shift assay showed that lysoPC increased
      the binding activity of CRE binding protein to tPACRE. These results indicated
      that lysoPC transcriptionally upregulated the gene expression of tPA in
      endothelial cells, at least in part, via tPACRE activation.

PMID- 15721276
TI  - n-Alkane and clofibrate, a peroxisome proliferator, activate transcription of
      ALK2 gene encoding cytochrome P450alk2 through distinct cis-acting promoter
      elements in Candida maltosa.
AB  - The ALK2 gene, encoding one of the n-alkane-hydroxylating cytochromes P450 in
      Candida maltosa, is induced by n-alkanes and a peroxisome proliferator,
      clofibrate. Deletion analysis of this gene's promoter revealed two cis-acting
      elements-an n-alkane-responsive element (ARE2) and a clofibrate-responsive
      element (CRE2)-that partly overlap in sequence but have distinct functions. ARE2
      mediated activation responded to n-alkanes but not to clofibrate and was
      repressed by glucose. CRE2-mediated activation responded to polyunsaturated fatty
      acids and steroid hormones as well as to peroxisome proliferators but not to n
      alkanes, and it was not repressed by glucose. Both elements mediated activation
      by oleic acid. Mutational analysis demonstrated that three CCG sequences in CRE2
      were critical to the activation by clofibrate as well as to the in vitro binding
      of a specific protein to this element. These findings suggest that ALK2 is
      induced by peroxisome proliferators and steroid hormones through a specific CRE2
      mediated regulatory mechanism.

PMID- 15721277
TI  - Protection of inactivated influenza virus vaccine against lethal influenza virus
      infection in diabetic mice.
AB  - Influenza virus infection frequently causes complications and some excess
      mortality in the patients with diabetes. Vaccination is an effective measure to
      prevent influenza virus infection. In this paper, antibody response and
      protection against influenza virus infection induced by vaccination were studied
      in mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized once
      or twice with inactivated influenza virus vaccine at various dosages. Four weeks
      after the first immunization or 1 week after the second immunization, the mice
      were challenged with influenza virus at a lethal dose. The result showed that the
      antibody responses in diabetic mice were inhibited. Immunization once with high
      dose or twice with low dose of vaccine provided full protection against lethal
      influenza virus challenge in diabetic mice, however, in healthy mice,
      immunization only once with low dose provided a full protection.

PMID- 15721278
TI  - Inhibition of NF-kappaB stabilizes gadd45alpha mRNA.
AB  - Growth arrest- and DNA damage-inducible protein alpha (gadd45alpha) is an
      important regulator for cell cycle, genomic stability, and cell apoptosis. In the
      present report, we demonstrated that NF-kappaB inhibition due to Ikkbeta
      deficiency enhanced the stability of gadd45alpha mNRA. Using embryo fibroblast
      cells derived from wild type (wt) or Ikkbeta gene knockout (Ikkbeta(-/-)) mice,
      reverse transcription-polymerase chain reaction revealed a three- to fourfold
      increase of gadd45alpha mRNA in Ikkbeta(-/-) cells compared with wt cells. The
      deficiency in Ikkbeta substantially decreased basal NF-kappaB activity and
      increased accumulation of reactive oxygen species (ROS). However, such deficiency
      had no effect on the basal expression or activity of Akt, FoxO3a, p53, and c-myc
      that regulate the transcription of gadd45alpha gene positively or negatively.
      Analysis of gadd45alpha mRNA stability showed a ROS-dependent increase in the
      half-life of gadd45alpha mRNA in Ikkbeta(-/-) cells. Immunoprecipitation
      experiments indicated an increased binding of a RNA stabilizing protein,
      nucleolin, to gadd45alpha mRNA in Ikkbeta(-/-) cells. The binding of nucleolin to
      gadd45alpha mRNA could be prevented by the antioxidant, N-acetyl-cysteine. Thus,
      these data are the first to suggest that inhibition of Ikkbeta-NF-kappaB
      signaling up-regulates the expression of gadd45alpha mNRA through a post
      transcriptional, rather than a transcriptional, mechanism.

PMID- 15721279
TI  - GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer
      patients.
AB  - Androgens have an anti-proliferative effect on endometrial cells. Human androgen
      receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG,
      and a single-nucleotide polymorphism on exon 1 that is recognized by the
      restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG
      repeat are inversely and linearly related to AR activity and associated with
      endometrial cancer. However, little is known about the GGC repeat and the StuI
      polymorphism of the AR gene. Thus, we investigated whether these AR polymorphisms
      are risk factors for endometrial cancer. To test this hypothesis, the genetic
      distributions of these polymorphisms were investigated in blood samples from
      endometrial cancer patients and healthy controls. The allelic and genotyping
      profiles were analyzed by polymerase chain reaction (PCR), PCR-restriction
      fragment length polymorphism (PCR-RFLP), and direct DNA sequencing, and analyzed
      statistically. The GGC repeat was significantly longer in endometrial cancer
      patients as compared to normal healthy controls. In general, an increased risk of
      endometrial cancer was found with increasing GGC repeat. The relative risk for
      the 17 GGC repeat was greater than 4, as compared to controls. However, the StuI
      polymorphism was not significantly different between patients and controls. The
      findings suggest that increased numbers of GGC repeat on the AR gene may be a
      risk factor for endometrial cancer.

PMID- 15721280
TI  - Effect of matrix metalloproteinase inhibition on adipose tissue development.
AB  - The effect of Ro 28-2653, a synthetic matrix metalloproteinase (MMP) inhibitor,
      on adipose tissue development was studied in mice kept on a high fat diet (HFD).
      Five-week-old male wild-type (C57Bl/6J) mice were fed the HFD (42% kcal as fat,
      20.1 kJ/g) and received daily p.o. instillations of inhibitor (30 mg/kg) or
      vehicle. After 15 weeks of the HFD, the body weight gain was lower in the
      inhibitor-treated group (7.4 +/- 0.88 g versus 10 +/- 1.4 g) whereas the weights
      of the isolated subcutaneous (SC) or gonadal (GON) fat deposits were 10-15%
      lower. The number of adipocytes in adipose tissues of the inhibitor-treated mice
      was somewhat higher (10-17%) but their diameter was smaller (about 10%). In situ
      zymography showed reduced gelatinolytic activity in SC (about 2.7-fold) and GON
      (1.4-fold) adipose tissue of inhibitor-treated mice, whereas their fibrillar
      collagen content was higher (1.5- and 4.7-fold, respectively). In both SC and GON
      adipose tissues of inhibitor-treated mice, MMP-2 (gelatinase A) and MMP-14
      (membrane type-1 MMP) were 2- to 3-fold upregulated, whereas MMP-9 (gelatinase B)
      mRNA levels were not affected. Thus, in this in vivo model partial inhibition of
      gelatinolytic activity is associated with moderate effects on adipose tissue
      development and cellularity. Possibly, enhanced MMP expression to some extent
      counteracts the in vivo effect of the inhibitor in adipose tissue.

PMID- 15721281
TI  - Purification and properties of a low molecular weight 1,4-beta-d-glucan
      glucohydrolase having one active site for carboxymethyl cellulose and xylan from
      an alkalothermophilic Thermomonospora sp.
AB  - A low molecular weight 1,4-beta-D-glucan glucohydrolase from an extracellular
      culture filtrate of Thermomonospora sp. was purified to homogeneity. The
      molecular weight of the purified enzyme was 14.2 kDa by MALDI-TOF analysis and is
      in agreement with SDS-PAGE and gel filtration chromatography. The purified enzyme
      exhibited both endocarboxymethyl cellulase and endoxylanase activities. A kinetic
      method was employed to study the active site of the enzyme that hydrolyzes both
      carboxymethyl cellulose and xylan. The experimental data coincide well with the
      theoretical values calculated for the case of a single active site. Conformation
      and microenvironment at the active site was probed with fluorescent chemo
      affinity labeling using o-phthalaldehyde as the chemical initiator. Formation of
      isoindole derivative resulted in complete inactivation of the enzyme to hydrolyze
      both xylan and CMC as judged by fluorescence studies corroborating a single
      active site for the hydrolysis of xylan and CMC.

PMID- 15721282
TI  - Synaptic proteins and SNARE complexes are localized in lipid rafts from rat brain
      synaptosomes.
AB  - The biochemical characterization of the SNARE proteins present in lipid
      microdomains, also known as "lipid rafts," has been addressed in earlier studies,
      with conflicting data from different laboratories. In this study, we use rat
      brain synaptosomes as a model with which to examine the presence of proteins
      involved in exocytosis in detergent-resistant membranes (DRM), also known as
      'lipid rafts.' By means of buoyancy analysis in sucrose gradients of Triton X-100
      solubilized synaptosomes, we identified a pool of SNARE proteins (SNAP 25,
      syntaxin 1, and synaptobrevin2/VAMP2) significantly associated with DRM.
      Furthermore, Munc18, synaptophysin, and high amounts of the isoforms I and II of
      synaptotagmin were also found in DRM. In addition, SDS-resistant and temperature
      dependent SNARE complexes were also detected in DRM. Treatment of synaptosomes
      with methyl-beta-cyclodextrin resulted in persistence of the proteins present in
      the DRM isolated using Triton X-100, whilst strongly impairing calcium-dependent
      glutamate release. The results from the present work show that lipid microdomains
      are sites where SNARE proteins and complexes are actually present, as well as
      important elements in the control of regulated exocytosis.

PMID- 15721283
TI  - Anti-inflammatory roles of retinoic acid in rat brain astrocytes: Suppression of
      interferon-gamma-induced JAK/STAT phosphorylation.
AB  - The anti-inflammatory effect of retinoic acid (RA) has been investigated for
      several decades. However, the underlying mechanisms responsible for this effect
      are largely unknown. In this study, we demonstrate that 9-cis-RA (cRA) and all
      trans-RA (tRA) inhibit interferon-gamma (IFN-gamma)-induced inflammatory
      responses in astrocytes. In primary cultured rat brain astrocytes and C6
      astroglioma cells, both cRA and tRA decreased IFN-gamma-induced expression of
      interferon regulatory factor-1. Both RA isoforms also reduced IFN-gamma-induced
      activation of signal transducers and activators of transcription (STAT)1, STAT3,
      Janus kinase (JAK)1, and JAK2. This inhibitory effect was significant when cells
      were pre-treated with RA prior to IFN-gamma. Furthermore, the effect of pre
      treated RA was abolished in the presence of cycloheximide, indicating a
      requirement for de novo protein synthesis. Suppressors of cytokine signaling
      (SOCS), which are negative regulators of the JAK/STAT pathway, may be candidate
      mediators of the anti-inflammatory function of RA. Both cRA and tRA induced SOCS3
      mRNA expression. These results suggest that RA induces an anti-inflammatory
      effect by suppressing the activation of the JAK/STAT pathway in IFN-gamma-treated
      astrocytes. SOCS3 may be at least one of the mechanisms that mediate the anti
      inflammatory roles of RA.

PMID- 15721284
TI  - CD83 is a dimer: Comparative analysis of monomeric and dimeric isoforms.
AB  - Recently, we reported that soluble CD83 has a strong immunosuppressive activity
      in vitro as well as in vivo. Sequence alignment of CD83 between different species
      revealed the presence of five cysteines in the extracellular Ig-domain of the
      protein. This opens up the possibility that four cysteines are involved in the
      formation of two intramolecular disulfide bonds and a possible involvement of the
      remaining fifth cysteine in the formation of an intermolecular covalent disulfide
      bond, leading to the dimerization of the extracellular protein domains. Using
      recombinant mutational analyses, where the fifth cytosine at amino acid position
      129 was mutated to a serine, we could prove that the fifth cysteine residue was
      indeed necessary for the dimerization. Functional analyses revealed that the
      mutant protein inhibited almost completely the upregulation of CD83-expression
      during DC maturation. Furthermore, the functional activity of the mutant protein
      was investigated using MLR assays and we could show that the mutant soluble CD83
      protein inhibited DC-mediated allogeneic T-cell stimulation in vitro.

PMID- 15721285
TI  - Isolation of CHO-K1 clones defective in cAMP-dependent proteolysis, as determined
      by the stability of exogenously expressed GATA-6.
AB  - Degradation of the GATA-6(Delta50) protein expressed in a CHO-K1 clone (tc1-17a)
      is stimulated in the presence of dbcAMP through proteasome without new protein
      synthesis [FEBS Lett. 408 (1997) 301], whereas the intrinsic GC-box-binding
      protein was stable. To examine the cellular mechanism responsible for this
      specific degradation of GATA-6(Delta50), we initially introduced the blasticidin
      S deaminase gene carrying a promoter with GATA motifs that are recognized by GATA
      6. The resulting cell line (tc2G2) grew in the presence of blasticidin S.
      However, the presence of both blasticidin S and dbcAMP was lethal due to
      degradation of GATA-6. Cells resistant to such lethality were isolated by
      chemical mutagenesis. The GATA-6(Delta50) in these resistant cells was stable in
      the presence of dbcAMP in contrast to that in the parent tc2G2 cells, as
      determined by gel-mobility shift analysis and Western blotting. These clones
      could be beneficial for identification and characterization of the components
      participating in the signaling pathway for both protein degradation and cAMP
      dependent biological processes.

PMID- 15721286
TI  - Selenocysteine tRNA identification in the model organisms Dictyostelium
      discoideum and Tetrahymena thermophila.
AB  - Characterizing Sec tRNAs that decode UGA provides one of the most direct and
      easiest means of determining whether an organism possesses the ability to insert
      selenocysteine (Sec) into protein. Herein, we used a combination of two
      techniques, computational to identify Sec tRNA genes and RT-PCR to sequence the
      gene products, to unequivocally demonstrate that two widely studied, model
      protozoans, Dictyostelium discoideum and Tetrahymena thermophila, encode Sec tRNA
      in their genomes. The advantage of using both procedures is that computationally
      we could easily detect potential Sec tRNA genes and then confirm by sequencing
      that the Sec tRNA was present in the tRNA population, and thus the identified
      gene was not a pseudogene. Sec tRNAs from both organisms decode UGA. T.
      thermophila Sec tRNA, like all other sequenced Sec tRNAs, is 90 nucleotides in
      length, while that from D. discoideum is 91 nucleotides long making it the
      longest eukaryotic sequenced to date. Evolutionary analyses of known Sec tRNAs
      reveal the two forms identified herein are the most divergent eukaryotic Sec
      tRNAs thus far sequenced.

PMID- 15721287
TI  - Solution structure of humanin, a peptide against Alzheimer's disease-related
      neurotoxicity.
AB  - Humanin is a newly identified 24-residue peptide that suppresses neuronal cell
      death caused by a wide spectrum of familial Alzheimer's disease genes and the
      beta-amyloid peptide. In this study, NMR and circular dichroism studies of
      synthetic humanin in aqueous and 30% 2,2,2-trifluoroethanol (TFE) solutions are
      reported. In aqueous solution, humanin exists predominantly in an unstructured
      conformation in equilibrium with turn-like structures involving residues Gly5 to
      Leu10 and Glu15 to Leu18, providing indication of nascent helix. In the less
      polar environment of 30% TFE, humanin readily adopts helical structure with long
      range order spanning residues Gly5 to Leu18. Comparative 3D modeling studies and
      topology predictions are in qualitative agreement with the experimental findings
      in both environments. Our studies reveal a flexible peptide in aqueous
      environment, which is free to interact with possible receptors that mediate its
      action, but may also acquire a helical conformation necessary for specific
      interactions and/or passage through membranes.

PMID- 15721288
TI  - Regulation of yeast glycogen phosphorylase by the cyclin-dependent protein kinase
      Pho85p.
AB  - Yeast accumulate glycogen in response to nutrient limitation. The key enzymes of
      glycogen synthesis and degradation, glycogen synthase, and phosphorylase, are
      regulated by reversible phosphorylation. Phosphorylation inactivates glycogen
      synthase but activates phosphorylase. The kinases and phosphatases that control
      glycogen synthase are well characterized whilst the enzymes modifying
      phosphorylase are poorly defined. Here, we show that the cyclin-dependent protein
      kinase, Pho85p, which we have previously found to regulate glycogen synthase also
      controls the phosphorylation state of phosphorylase.

PMID- 15721289
TI  - Engineering and characterization of a divalent single-chain Fv angiotensin II
      fusion construct of the monoclonal antibody CC49.
AB  - For the therapy of solid tumors, co-administration of angiotensin II (AngII)
      results in an increased uptake of drugs into the tumor interstitium. We have
      engineered a dimeric sc(Fv)(2)-AngII fusion construct that combines the superior
      kinetics of covalent dimeric scFvs [sc(Fv)(2)], recognizing the pancarcinoma
      tumor-associated antigen 72 (TAG-72), with the advantageous intrinsic activity of
      AngII. The binding characteristics of the fusion construct were unaltered by the
      addition of the AngII sequence [affinity constant K(A) 1.18 x 10(7) and 8.42 x
      10(6) M(-1) for sc(Fv)(2) and sc(Fv)(2)-AngII, respectively]. The binding of the
      fusion construct to the angiotensin receptor (AT(1)) was similar to AngII, and
      the arterial contraction was 16 +/- 1% of the response observed with
      norepinephrine. In animal studies, the radiolabeled sc(Fv)(2)-AngII construct
      exhibited similar uptake and a more homogeneous distribution within the tumor as
      compared to sc(Fv)(2).

PMID- 15721290
TI  - Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts.
AB  - To explore the mechanism of glucocorticoid-induced osteoporosis, we investigated
      the effect of glucocorticoid on canonical Wnt signaling that emerged as a novel
      key pathway for promoting bone formation. Wnt3a increased the T-cell factor
      (Tcf)/lymphoid enhancer factor (Lef)-dependent transcriptional activity in
      primary cultured human osteoblasts. Dexamethasone suppressed this transcriptional
      activity in a dose-dependent manner, while 1,25-dihydroxyvitamin D3 increased
      this transcriptional activity. LiCl, an inhibitor of glycogen synthase kinase
      3beta, also enhanced the Tcf/Lef-dependent transcriptional activity, which was,
      however, not inhibited by dexamethasone. The addition of anti-dickkopf-1 antibody
      partially restored the transcriptional activity suppressed by dexamethasone.
      Dexamethasone decreased the cytosolic amount of beta-catenin accumulated by Wnt3a
      and also inhibited the nuclear translocation of beta-catenin induced by Wnt3a.
      These data suggest that glucocorticoid suppresses the canonical Wnt signal in
      cultured human osteoblasts, partially through the enhancement of the dickkopf-1
      production.

PMID- 15721291
TI  - Stimulation of hepatocyte survival and suppression of CCl4-induced liver injury
      by the adenovirally introduced C/EBPbeta gene.
AB  - Gene therapy has attracted attention as a potentially effective alternative to
      liver transplantation for the treatment of hepatic failure. We chose the
      C/EBPbeta gene, which plays vital roles in liver regeneration, as a candidate for
      gene therapy, and examined its effect on hepatocyte survival and the suppression
      of liver inflammation. C/EBPbeta gene overexpression significantly maintained
      hepatocyte viability during 12 days of the culture. Urea synthesis ability, which
      is a liver-specific function, in Adv-C/EBPbeta-infected hepatocytes was stably
      maintained during the culture, but the activity per cell was significantly lower
      than that in non-infected cells. On the contrary, DNA synthesis activity in Adv
      C/EBPbeta-infected hepatocytes was significantly higher than that in non-infected
      cells. COX-2 was induced in Adv-C/EBPbeta-infected hepatocytes, and the addition
      of NS398, a specific inhibitor of COX-2, suppressed the viability-maintenance
      effect. COX-2 was thus shown to be involved in the survival effect of C/EBPbeta
      gene. The introduction of the C/EBPbeta gene into liver-damaged mice
      significantly suppressed the serum AST and ALT activities. These results indicate
      that C/EBPbeta appears to be a survival factor under stressful conditions, and
      the introduction of the gene has therapeutic function against liver injury.

PMID- 15721293
TI  - Multiple functions of the vacuolar sorting protein Ccz1p in Saccharomyces
      cerevisiae.
AB  - The CCZ1 (YBR131w) gene encodes a protein required for fusion of various
      transport intermediates with the vacuole. Ccz1p, in a complex with Mon1p, is a
      close partner of Ypt7p in the processes of fusion of endosomes to vacuoles and
      homotypic vacuole fusion. In this work, we exploited the Ca(2+)-sensitivity of
      the ccz1Delta mutant to identify genes specifically interacting with CCZ1, basing
      on functional multicopy suppression of calcium toxicity. The presented results
      indicate that Ccz1p functions in the cell either in association with Mon1p and
      Ypt7p in fusion at the vacuolar membrane, or--separately--with Arl1p at early
      steps of vacuolar transport. We also show that suppression of calcium toxicity by
      the calcium pumps Pmr1p and Pmc1p is restricted only to the subset of mutants
      defective in vacuole morphology. The mechanisms of Ca(2+)-pump-mediated
      suppression also differ from each other, since the action of Pmr1p, but not
      Pmc1p, appears to require Arl1p function.

PMID- 15721292
TI  - Involvement of specific proteins (Sp1/Sp3) and nuclear factor Y in basal
      transcription of the distal promoter of the rat pyruvate carboxylase gene in beta
      cells.
AB  - Pyruvate carboxylase plays diverse roles in different biosynthetic pathways,
      including glucose-induced insulin secretion in pancreatic beta-cells. We have
      localized the control region of the P2 promoter by generating a series of 5'
      nested deletion constructs, and both 25- and 9-bp internal deletion constructs,
      as well as by performing site-directed mutagenesis. Transient transfections of
      these constructs into INS-1 cells identified a CCAAT box and a GC box that are
      located at -65/-61 and -48/-41, respectively, as the important determinants.
      Disruption of the GC box resulted in a 4-fold reduction of the reporter activity,
      while disruption of the proximal CCAAT box (-65/-61) but not the distal CCAAT box
      (-95/-91) increased the reporter activity by 3-fold. Simultaneous disruptions of
      both the GC box and the CCAAT box reduced the reporter activity to a level that
      was close to that of the single GC box mutation. Electrophoretic mobility shift
      assays (EMSAs) and supershift EMSAs using nuclear extract from INS-1 cells
      demonstrated that Sp1 and Sp3 bind a GC box while the nuclear factor Y was shown
      to bind the proximal but not the distal CCAAT box.

PMID- 15721294
TI  - Association of the ABCA1 gene polymorphisms with type 2 DM in a Japanese
      population.
AB  - To examine the association of the ATP-binding cassette transporter 1 (ABCA1) gene
      with type 2 diabetes (DM), we studied genetic polymorphisms of the ABCA1 gene
      including its linkage disequilibrium (LD) and haplotype analyses using a Japanese
      population. A sample set (DM:72, IGT:75, and NGT:227) was genotyped with 34 SNPs
      distributed from the promoter region to the last exon of the ABCA1 gene. LD
      between SNPs was assessed in pairwise manner. Among 13 LD blocks constructed, an
      LD block at the 5'-region showed a significant difference in the haplotype
      distribution between the study groups (NGT vs. IGT + DM: overall p = 0.0180; NGT
      vs. DM: 0.0001). Fisher's exact probability test (NGT vs. DM) showed a
      significant association of the haplotype 2 of the LD block (p = 0.0001), with an
      odds ratio (OR) of 2.53 (95%CI:1.62-4.12). Diplotype analysis also showed a
      significant association of the diplotypes with the haplotype 2 (OR:2.59,
      95%CI:1.48-4.54, p = 0.0013).

PMID- 15721295
TI  - Phosphorylation-dependent binding of 14-3-3 to Par3beta, a human Par3-related
      cell polarity protein.
AB  - Mammalian Par3alpha and Par3beta/Par3L participate in cell polarity establishment
      and localize to tight junctions of epithelial cells; Par3alpha acts via binding
      to atypical PKC (aPKC). Here we show that Par3beta as well as Par3alpha interacts
      with 14-3-3 proteins in a phosphorylation-dependent manner. In the interaction,
      Ser-746 of Par3beta and the corresponding residue of Par3alpha (Ser-814) likely
      play a crucial role, since replacement of these residues by unphosphorylatable
      alanine results in a loss of interacting activity. The mutant Par3 proteins with
      the replacement are correctly recruited to tight junctions of MDCK cells and to
      membrane ruffles induced by an active form of the small GTPase Rac in HeLa cells.
      Thus, the interaction with 14-3-3 appears to be dispensable to Par3 localization.
      Consistent with this, the Par3alpha-14-3-3 interaction does not inhibit the
      Par3alpha-aPKC association required for the Par3alpha localization, although the
      aPKC-binding site lies close to the Ser-814-containing, 14-3-3-interacting
      region.

PMID- 15721296
TI  - Synthesis of universal unmethylated control DNA by nested whole genome
      amplification with phi29 DNA polymerase.
AB  - Optimization of highly sensitive methods to detect methylation of CpG islands in
      gene promoter regions requires adequate methylated and unmethylated control DNA.
      Whereas universal methylated control DNA is available, universal unmethylated
      control (UUC) DNA has not been made because demethylase is not available to
      remove methyl groups from all methylated cytosines. On the basis that DNA
      synthesized by DNA polymerase does not contain methylated cytosines, we developed
      a method to create UUC DNA by nested whole genome amplification (WGA) with phi29
      DNA polymerase. Contamination of the template genomic DNA in UUC was only 3.1 x
      10(-7), below the detection limit of sensitive methods used for methylation
      studies such as methylation-specific PCR. Assessment of microsatellite markers
      demonstrated that even nested phi29 WGA achieves highly accurate and homogeneous
      amplification with very low amounts of genomic DNA as an initial template. The
      UUC DNA created by nested phi29 WGA is practically very useful for methylation
      analysis.

PMID- 15721297
TI  - Inflammatory cytokines activate p38 MAPK to induce osteoprotegerin synthesis by
      MG-63 cells.
AB  - Inflammatory bone diseases are characterized by the presence of pro-inflammatory
      cytokines that regulate bone turnover. Osteoprotegerin (OPG) is a soluble
      osteoblast-derived protein that influences bone resorption by inhibiting
      osteoclast differentiation and activation. In the present study, we demonstrate
      that interleukin-1beta and tumor necrosis factor alpha induce OPG mRNA production
      and OPG secretion by osteoblast-like MG-63 cells. Maximum induction of OPG
      secretion by either cytokine requires activation of the p38 mitogen activated
      protein kinase (MAPK) pathway but neither the p42/p44 (ERK) nor the c-Jun N
      terminal MAPK pathways. Induction of OPG mRNA by either cytokine is also p38 MAPK
      dependent. Taken together, these data indicate that cytokine-induced OPG gene
      expression and protein secretion are differentially regulated by specific MAP
      kinase signal transduction pathways.

PMID- 15721298
TI  - Resistance to influenza A virus infection by antigen-conjugated CpG
      oligonucleotides, a novel antigen-specific immunomodulator.
AB  - Oligodeoxynucleotides (ODN) containing CpG motifs (CpG) act as modulators that
      bias the immune response towards a Th1-dominant phenotype. To investigate this
      effect further, we examined the protective effects of a covalently linked
      conjugate between CpG-ODN and HA-2kd antigen in mice infected with influenza A
      virus. The conjugated form of CpG-ODN and HA-2kd was more efficient in regulating
      influenza A virus than the unconjugated mixture of CpG-ODN and HA-2kd. The
      antigen-conjugated CpG-ODN induced an immune response with a Th1-dominant
      cytokine pattern characterized by the secretion of high levels of HA-2kd-specific
      interferon-gamma and IgG2a (Th1), which were only slightly induced by HA-2kd
      alone. These findings support the use of CpG-ODN-Ag conjugates as novel Ag
      specific immunomodulators and suggest that CpG-ODN-HA-2kd might be a promising
      immune therapy for patients with influenza virus.

PMID- 15721299
TI  - Plasminogen/plasmin regulates c-fos and egr-1 expression via the MEK/ERK pathway.
AB  - In this study, we showed that plasminogen (Plg) and plasmin (Pla) bind to lysine
      binding sites on cell surface and trigger a signaling pathway that activates the
      mitogen-activated protein kinase (MAPK) MEK and ERK1/2, which in turn leads to
      the expression of the primary response genes c-fos and early growth response gene
      egr-1. Our data show that the Plg/Pla-stimulated steady-state mRNA levels of both
      genes reached a maximum by 30 min and then returned to basal levels by 1h. The
      gene induction was sensitive to both pharmacological and genetic inhibition of
      MEK. Leupeptin, a serine protease inhibitor, suppressed Pla but not Plg-induced c
      fos and egr-1 expression, emphasizing the role played by the serine protease
      activity associated with Pla. Pre-incubation with cholera toxin completely
      blocked the Plg/Pla-induced gene expression, suggesting that another signaling
      pathway, which recruits G protein-coupled receptors, may also be involved.
      Furthermore, Plg/Pla also stimulated AP-1 and EGR-1 DNA-binding activities, which
      were abrogated by pharmacological inhibition of MEK. Altogether, these results
      suggest that Plg/Pla stimulates c-fos and egr-1 expression via activation of the
      MEK/ERK pathway.

PMID- 15721300
TI  - Analysis of self-association of West Nile virus capsid protein and the crucial
      role played by Trp 69 in homodimerization.
AB  - The understanding of capsid (C) protein interactions with itself would provide
      important data on how the core is organized in flaviviruses during assembly. In
      this study, West Nile (WN) virus C protein was shown to form homodimers using
      yeast two-hybrid analysis in conjunction with mammalian two-hybrid and in vivo co
      immunoprecipitation assays. To delineate the region on the C protein which
      mediates C-C dimerization, truncation studies were carried out. The results
      obtained clearly showed that the internal hydrophobic segment flanked by helix I
      and helix III of WN virus C protein is essential for the self-association of C
      protein. The crucial role played by Trp 69 in stabilizing the self-association of
      C protein was also demonstrated by mutating Trp to Gly/Arg/Phe. Substitution of
      the Trp residue with Gly/Arg abolished the dimerization, whereas substitution
      with Phe decreased the self-association significantly. The results of this study
      pinpoint a critical residue in the C protein that potentially plays a role in
      stabilizing the homotypic interaction.

PMID- 15721301
TI  - Quantitative measurement of changes in adhesion force involving focal adhesion
      kinase during cell attachment, spread, and migration.
AB  - Focal adhesion kinase (FAK) is a critical protein for the regulation of integrin
      mediated cellular functions and it can enhance cell motility in Madin-Darby
      canine kidney (MDCK) cells by hepatocyte growth factor (HGF) induction. We
      utilized optical trapping and cytodetachment techniques to measure the adhesion
      force between pico-Newton and nano-Newton (nN) for quantitatively investigating
      the effects of FAK on adhesion force during initial binding (5 s), beginning of
      spreading (30 min), spreadout (12 h), and migration (induced by HGF) in MDCK
      cells with overexpressed FAK (FAK-WT), FAK-related non-kinase (FRNK), as well as
      normal control cells. Optical tweezers was used to measure the initial binding
      force between a trapped cell and glass coverslide or between a trapped bead and a
      seeded cell. In cytodetachment, the commercial atomic force microscope probe with
      an appropriate spring constant was used as a cyto-detacher to evaluate the change
      of adhesion force between different FAK expression levels of cells in spreading,
      spreadout, and migrating status. The results demonstrated that FAK-WT
      significantly increased the adhesion forces as compared to FRNK cells throughout
      all the different stages of cell adhesion. For cells in HGF-induced migration,
      the adhesion force decreased to almost the same level (approximately 600 nN)
      regardless of FAK levels indicating that FAK facilitates cells to undergo
      migration by reducing the adhesion force. Our results suggest FAK plays a role of
      enhancing cell adhesive ability in the binding and spreading, but an appropriate
      level of adhesion force is required for HGF-induced cell migration.

PMID- 15721302
TI  - Phorbol ester phorbol-12-myristate-13-acetate promotes anchorage-independent
      growth and survival of melanomas through MEK-independent activation of ERK1/2.
AB  - The phorbol ester, phorbol-12-myristate-13-acetate (PMA), an activator of PKCs,
      is known to stimulate the in vitro growth of monolayer cultures of normal human
      melanocytes whereas it inhibits the growth of most malignant melanoma cell lines.
      We examined the effect of PMA on proliferation and survival of melanoma cells
      grown as multicellular aggregates in suspension (spheroids), and aimed to
      elucidate downstream targets of PKC signaling. In contrast to monolayer cultures,
      PMA increased cell proliferation as well as protected melanoma cells from
      suspension-mediated apoptosis (anoikis). Supporting the importance of PKC in
      anchorage-independent growth, treatment of anoikis-resistant melanoma cell lines
      with antisense oligonucleotides against PKC-alpha, or the PKC inhibitor Go6976,
      strongly induced anoikis. PMA induced activation of ERK1/2, but this effect was
      not prevented by the MEK inhibitors PD98059 or by U0126. Whereas PD98059
      treatment alone led to marked activation of the pro-apoptotic Bim and Bad
      proteins and significantly increased anoikis, these effects were clearly reversed
      by PMA. In conclusion, our results indicate that the protective effect of PMA on
      anchorage-independent survival of melanoma cells at least partly is mediated by
      MEK-independent activation of ERK1/2 and inactivation of downstream pro-apoptotic
      effector proteins.

PMID- 15721303
TI  - Glucose-induced serum- and glucocorticoid-regulated kinase activation in
      oncofetal fibronectin expression.
AB  - Preferential expression of oncofetal extra domain-B fibronectin (EDB(+) FN), a
      proposed angiogenic marker, has been shown in proliferative diabetic retinopathy.
      High levels of glucose also increase EDB(+) FN expression in endothelial cells
      (ECs) via transforming growth factor-beta1 (TGF-beta1) and endothelin-1 (ET-1).
      The present study was aimed at elucidating the role of serum- and glucocorticoid
      regulated kinase (SGK-1) in glucose-induced EDB(+) FN expression. Using human
      macro- and microvascular ECs, we show that high levels of glucose, TGF-beta1, and
      ET-1 increase the EDB(+) FN expression via SGK-1 alteration at the mRNA, protein,
      and activity levels. Inhibition of TGF-beta1 and ET-1 prevented glucose-induced
      SGK-1 activation and the EDB(+) FN expression. Furthermore, using siRNA-mediated
      SGK-1 gene silencing, we show that glucose-induced EDB(+) FN expression can be
      completely prevented. These findings provide first evidence of glucose-induced
      SGK-1 activation in altered EDB(+) FN expression and provide novel avenues for
      therapeutic modalities.

PMID- 15721304
TI  - Successful expression of a functional yeast G-protein-coupled receptor (Ste2) in
      mammalian cells.
AB  - G-protein-coupled receptors (GPCRs) are membrane-embedded cell signaling devices
      transducing ligand binding to activation of heterotrimeric G-proteins, providing
      a paradigm for signaling for yeast and mammals alike. Probing the extent to which
      yeast GPCRs may couple to mammalian G-proteins has been problematic. In the
      current work, we explored conditions that enable the cell-surface expression of a
      yeast alpha-factor pheromone receptor (Ste2). When expressed in human HEK293
      cells, Ste2 is shown to bind its ligand alpha-factor, to be functional and
      catalyze activation of the mitogen-activated protein kinase cascade, and to
      demonstrate agonist-induced internalization. In response to agonist Ste2 as
      maintained intracellularly for several hours and avoids the degradation process
      observed for Ste2 in yeast cells. This is the first successful demonstration of
      the ability to express a functional yeast GPCR in mammalian cells.

PMID- 15721305
TI  - Development of new inbred transgenic strains of rats with LacZ or GFP.
AB  - The ideal goal of regeneration medicine is to restore form and function to
      damaged tissues. While stem cell transplantation is considered a promising
      therapeutic approach, knowing the fate of transplanted cells using appropriate
      markers is essential. We developed new inbred transgenic rat strains with lacZ
      and GFP based on the transgenic (Tg) animal technique in rats. These Tg animals
      expressed most of their marker genes ubiquitously, compared to previous Tg rats.
      Immunological antigenicity against marker proteins was evaluated using
      conventional skin grafting, and results suggested lacZ-Tg-derived skin was much
      less immunogenic than that of GFP-Tg. However, GFP-positive cells from parental
      transgenic rats were still potential candidates for the study of cellular fate in
      immune privilege sites, such as the brain. Taking advantage of less immunogenic
      lacZ, we also examined the role of bone marrow-derived cells (BMDCs) in skin
      wound healing using an in vivo biological imaging system. Although
      transplantation of BMDCs enhanced wound healing at the injection site, BMDCs were
      detected only for a short time, suggesting a transient contribution of autologous
      BMDC-transplantation in wound healing. Our Tg-rat system may provide great
      benefits for the elucidation of the cellular process of regenerative medicine,
      including cell and tissue transplantation.

PMID- 15721306
TI  - Increase of smooth muscle cell migration and of intimal hyperplasia in mice
      lacking the alpha/beta hydrolase domain containing 2 gene.
AB  - Multiple steps, including the migration of vascular smooth muscle cells (SMCs),
      are involved in the pathogenesis of atherosclerosis. To discover genes which are
      involved in these steps, we screened mutant mouse lines established by the
      exchangeable gene trap method utilizing X-gal staining during their embryonic
      development. One of these lines showed strong reporter gene expression in the
      vitelline vessels of yolk sacs at embryonic day (E) 12.5. The trap vector was
      inserted into the fifth intron of alpha/beta hydrolase domain containing 2
      (Abhd2) gene which was shown to be expressed in vascular and non-vascular SMCs of
      adult mice. Although homozygous mutant mice were apparently normal, enhanced SMC
      migration in the explants SMCs culture and marked intimal hyperplasia after cuff
      placement were observed in homozygous mice in comparison with wild-type mice. Our
      results show that Abhd2 is involved in SMC migration and neointimal thickening on
      vascular SMCs.

PMID- 15721307
TI  - Integrin alpha8beta1-fibronectin interactions promote cell survival via PI3
      kinase pathway.
AB  - Integrin signaling plays a critical role in many aspects of normal growth,
      differentiation, and injury response. In the adult, alpha8beta1 is expressed in
      alveolar myofibroblasts and is upregulated in pulmonary fibrosis and other models
      of organ injury. Following injury, survival of fibronectin-producing
      myofibroblasts cells is an important determinant of development of fibrosis.
      Using stable alpha8-transfected cell lines, we show that interactions of
      alpha8beta1 with its ligand, fibronectin, promote cell survival during serum
      deprivation. Multiple cell signaling pathways were activated following
      fibronectin adhesion, including PI3 kinase and MAP kinase. However, the alpha8
      mediated cell survival was blocked by LY294002, a PI3 kinase inhibitor, but not
      by staurosporine, a PKC inhibitor, or PD98059, a MAPK kinase inhibitor. A
      dominant negative construct of PI3 kinase also inhibited alpha8-mediated cell
      survival. Therefore, alpha8-mediated survival appears to be mediated by the PI3
      kinase pathway. Survival of alpha8-expressing myofibroblasts may contribute to
      persistent fibrosis following injury.

PMID- 15721308
TI  - Screening of LPS-specific peptides from a phage display library using epoxy
      beads.
AB  - The selection of identical or highly homologous peptides from phage display
      combinatorial peptide libraries has been unsuccessful in biopanning experiments
      using microtiter plates. In the present study, by biopanning on LPS-conjugated
      epoxy beads, we repeatedly enriched clones encoding AWLPWAK and NLQEFLF. These
      peptides were found to interact with the polysaccharide moiety of LPS, which is
      highly variable among gram negative bacterial species. In addition, phages
      encoding these peptides preferentially bound to the LPS of Salmonella family.
      AWLPWAK-conjugated beads absorbed Salmonella enteritidis from solution and showed
      a preference for S. enteritidis over Escherichia coli. In summary, this study
      shows for the first time that a peptide screened from phage displays of
      combinatorial peptide libraries can be synthesized on beads and be used
      practically to concentrate bacterial cells from solution.

PMID- 15721309
TI  - Selective expression of a splice variant of decay-accelerating factor in c-erbB-2
      positive mammary carcinoma cells showing increased transendothelial invasiveness.
AB  - By differential-display-PCR a subclone of the SK-BR-3 cell line with high in
      vitro transendothelial invasiveness was identified to express increased levels of
      a new alternative splice variant of decay-accelerating factor (DAF). DAF seems to
      play an important role in some malignant tumours since on the one hand the
      expression of complement inhibitors on the surface of tumour cells prevents the
      accumulation of complement factors and in consequence cell lysis. On the other
      hand, DAF has been identified as a ligand for the CD97 surface receptor which
      induces cell migration. Immunofluorescence procedures, Western blot analyses, and
      cDNA clone sequencing were employed to confirm the expression of DAF restricted
      to invasive tumour cells. Using a radioactive RNA-in situ hybridisation on
      freshly frozen tissue microarrays and RT-PCR on native tumour tissue, the
      expression of alternative spliced DAF mRNA was demonstrated in invasive breast
      cancer. Due to the fact that it could thereby not be detected in normal mammary
      tissues, it has to be confirmed in larger studies that the DAF splice variant
      might be a specific tumour marker for invasive breast cancer.

PMID- 15721311
TI  - N-glycosylation is necessary for enzymatic activity of a beetle (Apriona germari)
      cellulase.
AB  - We previously reported that the beta-1,4-endoglucanase (EGase) belonging to
      glycoside hydrolase family 45 cloned from the mulberry longicorn beetle, Apriona
      germari (Ag-EGase I), is composed of 237 amino acid residues and has a potential
      N-glycosylation site at 97-100 amino acid residues (NSTF). We here describe the N
      glycosylation and its role for enzymatic activity of the Ag-EGase I. The N
      glycosylation of Ag-EGase I was revealed by the treatment of tunicamycin to the
      recombinant virus-infected insect Sf9 cells and by endoglycosidase F to the
      purified recombinant Ag-EGase I, demonstrating that the carbohydrate moieties are
      not necessary for secretion but essential for Ag-EGase I enzyme activity. To
      further elucidate the functional role of the N-glycosylation in Ag-EGase I, we
      have assayed the cellulase enzyme activity in Thr99Gln mutant. Lack of N
      glycosylation in Ag-EGase I showed no substantial enzyme activity. This result
      demonstrates that N-glycosylation at site 97-100 amino acid residues (NSTF) is
      essential for enzyme activity.

PMID- 15721310
TI  - Transcription regulation of the vegf gene by the BMP/Smad pathway in the
      angioblast of zebrafish embryos.
AB  - Vascular endothelial growth factor (VEGF) is a mitogen that is critically
      involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and
      how transcription factors participate in the regulation of vegf gene expression
      are not fully understood. Here we report the cloning and sequencing of the
      zebrafish vegf promoter which revealed that the promoter contains a number of
      bone morphogenetic protein (BMP)-activated Smad binding elements (SBE),
      implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf.
      Electrophoretic mobility shift assays of adding recombinant Smad proteins to the
      SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf
      promoter resulted in mobility shift of the oligonucleotides. These changes
      demonstrate potential interactions between Smad1/5 and the vegf promoter.
      Reporter activity assays using the wild-type or SBE-deleted vegf promoters to
      drive the luciferase reporter gene expression revealed that Smad1 stimulated
      while Smad5 repressed the vegf promoter activity in zebrafish embryos. These data
      indicate that the BMP/Smad signaling pathway is involved in the regulation of
      zebrafish vegf transcription. In addition, we demonstrate that transgenic
      expression of human BMP4 in zebrafish embryos induced an expansion of the
      posterior intermediate cell mass (ICM, also commonly called blood island), a
      population of cells containing endothelial and hematopoietic precursors. In the
      expanded ICM, vegf and VEGF receptor 2 (flk-1) were ectopically co-expressed,
      suggesting that an autocrine/paracrine regulation of vegf expression may exist
      and contribute to the BMP-induced hemangiogenic cell proliferation.

PMID- 15721312
TI  - Hepatic progenitor cell resistance to TGF-beta1's proliferative and apoptotic
      effects.
AB  - The success of hepatocellular therapies using stem or progenitor cell populations
      is dependent upon multiple factors including the donor cell, microenvironment,
      and etiology of the liver injury. The following experiments investigated the
      impact of TGF-beta1 on a previously described population of hepatic progenitor
      cells (HPC). The majority of the hepatic progenitor cells were resistant to
      endogenously produced TGF-beta1's proapoptotic and anti-proliferative effects
      unlike more well-differentiated cellular populations (e.g., mature hepatocytes).
      Surprisingly, in vitro TGF-beta1 supplementation significantly inhibited de novo
      hepatic progenitor cell colony formation possibly via an indirect mechanism(s).
      Therefore despite the HPC's direct resistance to supplemental TGF-beta1, this
      cytokine's inhibitory effect on colony formation could have a potential negative
      impact on the use of these cells as a therapy for patients with liver disease.

PMID- 15721313
TI  - Preferential binding of platelets to monocytes over neutrophils under flow.
AB  - This study was undertaken to systematically investigate the binding kinetics of
      platelet recruitment by monocytes relative to neutrophils in bulk suspensions
      subjected to shear as well as the molecular requirements of leukocyte-platelet
      binding. Hydrodynamic shear-induced collisions augment the proportion of
      monocytes with adherent platelets more drastically than that of neutrophils with
      bound platelets. These heterotypic interactions are further potentiated by
      platelet activation with thrombin or to a lesser extent by monocyte stimulation
      with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Monocyte-platelet
      heteroaggregation increases with increasing shear rate and shear exposure time.
      Platelet P-selectin binding to monocyte P-selectin-glycoprotein-ligand-1 is
      solely responsible for maximal platelet adhesion to unstimulated monocytes in
      shear flow. However, the enhanced platelet binding to fMLP-treated monocytes
      involves a sequential two-step process, wherein P-selectin-PSGL-1 interactions
      are stabilized by CD18-integrin involvement. Blocking platelet alpha(IIb)beta(3)
      or monocyte beta(1)-integrin function had no effect. This study underscores the
      preferential recruitment of platelets by monocytes relative to neutrophils in
      shear flow, and demonstrates that the shear environment of the vasculature
      coupled to the state of cell activation modulates the dynamics and molecular
      constituents mediating monocyte-platelet adhesion.

PMID- 15721314
TI  - Analysis of eluted peptides from type 1 diabetes-susceptible HLA class II
      molecules identified novel islet protein, heparin/heparan sulfate-interacting
      protein.
AB  - Identification of peptides derived from pancreatic islet and presented by type 1
      diabetes-susceptible MHC class II molecules has great significance to elucidate
      the pathogenesis of type 1 diabetes. A bulk culture of Epstein-Barr virus
      transformed B-cells, which were established from a 22-year-old type 1 diabetic
      woman with HLA-DR4 and -DQw8, was pulsed with the homogenate of a human embryonic
      pancreas-derived cell line 1B2C6, and another culture was not pulsed with
      antigen. Peptide fractions were obtained by treatment of affinity-purified HLA-DR
      and -DQ molecules with 0.1% trifluoroacetic acid, and were subjected to reverse
      phase high performance liquid chromatography (RP-HPLC). The RP-HPLC profiles of
      peptides derived from DR molecules revealed three peaks that specifically
      appeared after pulsing, but no such peaks were obtained from DQ molecules. From
      one of these three peaks, a peptide that consisted of 14 amino acids
      (AKSXNHTXXNQXRK, where X represents the undetermined amino acids) was identified.
      This peptide was derived from heparin/heparan sulfate-interacting protein (HIP).
      Immunostaining of pancreatic sections using antiserum for HIP peptide revealed
      exclusive staining of the islets. Thus, HIP was identified as an islet protein
      naturally processed and presented by HLA-DR4 molecules.

PMID- 15721315
TI  - Charge effects modulate actin assembly by classic myelin basic protein isoforms.
AB  - Myelin basic protein (MBP), a highly cationic structural protein of the myelin
      sheath, is believed to be associated with the cytoskeleton in vivo and interacts
      with actin in vitro, but little is known about the regulation of this
      interaction. The rate and extent of actin polymerization induced by 18.5 kDa MBP
      charge isomers were correlated to charge reduction by post-translational
      modifications. Increased ionic strength attenuated the initial rate but not the
      final extent of polymerization achieved. Reduced pH enhanced the rate and extent
      of polymerization, presumably via partial protonation of intrinsic histidyl
      residues. The polymerizing activities of the 21.5, 17, and 14 kDa MBP splice
      variants were not proportionate to their net charges or charge densities. The
      presence of at least one region derived from exon II or VI of the "classic" MBP
      gene was required for effective bundling as assessed by light scattering and
      transmission electron microscopy.

PMID- 15721316
TI  - Differential gene alteration among hepatoma cell lines demonstrated by cDNA
      microarray-based comparative genomic hybridization.
AB  - We assayed chromosomal abnormalities in hepatoma cell lines using the microarray
      based comparative genomic hybridization (array-CGH) method and investigated the
      relationship between genomic copy number alterations and expression profiles in
      these hepatoma cell lines. We modified a cDNA array-CGH assay to compare genomic
      DNAs from seven hepatoma cell lines, as well as DNA from two non-hepatoma cell
      lines and from normal cells. The mRNA expression of each sample was assayed in
      parallel by cDNA microarray. We identified small amplified or deleted chromosomal
      regions, as well as alterations in DNA copy number not previously described. We
      predominantly found alterations of apoptosis-related genes in Hep3B and HepG2,
      cell adhesion and receptor molecules in HLE, and cytokine-related genes in
      PLC/PRF/5. About 40% of the genes showing amplification or loss showed altered
      levels of mRNA (p < 0.05). Hierarchical clustering analysis showed that the
      expression of these genes allows differentiation between alpha-fetoprotein (AFP)
      producing and AFP-negative cell lines. cDNA array-CGH is a sensitive method that
      can be used to detect alterations in genomic copy number in tumor cells.
      Differences in DNA copy alterations between AFP-producing and AFP-negative cells
      may lead to differential gene expression and may be related to the phenotype of
      these cells.

PMID- 15721317
TI  - Mechanical stretch inhibits myoblast-to-adipocyte differentiation through Wnt
      signaling.
AB  - Myoblasts are able to differentiate into other mesenchymal lineages including
      adipocytes and osteoblasts. However, it is not known how this differentiation is
      normally regulated in intact animals and humans. Here, we subjected cultured
      C2C12 myoblasts to cyclic mechanical stretch (20% elongation) during
      differentiation into adipocytes. Mechanical stretch inhibited the myoblast-to
      adipocyte differentiation significantly, concurrent with an enhanced expression
      of Wnt10b mRNA. Inhibition of the Wnt signaling by incubation of the myoblasts
      with a soluble Wnt ligand, sFRP-2, abolished the inhibitory function of
      mechanical stretch on adipogenesis. These findings provide evidence that
      mechanical stretch inhibits myoblast-to-adipocyte differentiation possibly
      through Wnt signaling.

PMID- 15721318
TI  - Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine
      enteroendocrine cell line STC-1.
AB  - Bile acids play essential roles in the absorption of dietary lipids and in the
      regulation of bile acid biosynthesis. Recently, a G protein-coupled receptor,
      TGR5, was identified as a cell-surface bile acid receptor. In this study, we show
      that bile acids promote glucagon-like peptide-1 (GLP-1) secretion through TGR5 in
      a murine enteroendocrine cell line STC-1. In STC-1 cells, bile acids promoted GLP
      1 secretion in a dose-dependent manner. As STC-1 cells express TGR5 mRNA, we
      examined whether bile acids induce GLP-1 secretion through TGR5. RNA interference
      experiments showed that reduced expression of TGR5 resulted in reduced secretion
      of GLP-1. Furthermore, transient transfection of STC-1 cells with an expression
      plasmid containing TGR5 significantly enhanced GLP-1 secretion, indicating that
      bile acids promote GLP-1 secretion through TGR5 in STC-1 cells. Bile acids
      induced rapid and dose-dependent elevation of intracellular cAMP levels in STC-1
      cells. An adenylate cyclase inhibitor, MDL12330A, significantly suppressed bile
      acid-promoted GLP-1 secretion, suggesting that bile acids induce GLP-1 secretion
      via intracellular cAMP production in STC-1 cells.

PMID- 15721319
TI  - Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X
      receptor.
AB  - The pyruvate dehydrogenase complex (PDC) functions as an important junction in
      intermediary metabolism by influencing the utilization of fat versus carbohydrate
      as a source of fuel. Activation of PDC is achieved by phosphatases, whereas,
      inactivation is catalyzed by pyruvate dehydrogenase kinases (PDKs). The
      expression of PDK4 is highly regulated by the glucocorticoid and peroxisome
      proliferator-activated receptors. We demonstrate that the farnesoid X receptor
      (FXR; NR1H4), which regulates a variety of genes involved in lipoprotein
      metabolism, also regulates the expression of PDK4. Treatment of rat hepatoma
      cells as well as human primary hepatocytes with FXR agonists stimulates the
      expression of PDK4 to levels comparable to those obtained with glucocorticoids.
      In addition, treatment of mice with an FXR agonist significantly increased
      hepatic PDK4 expression, while concomitantly decreasing plasma triglyceride
      levels. Thus, activation of FXR may suppress glycolysis and enhance oxidation of
      fatty acids via inactivation of the PDC by increasing PDK4 expression.

PMID- 15721320
TI  - Tumor necrosis factor (TNF) interferes with insulin signaling through the p55 TNF
      receptor death domain.
AB  - Tumor necrosis factor (TNF) contributes to insulin resistance by binding to the
      55kDa TNF receptor (TNF-R55), resulting in serine phosphorylation of proteins
      such as insulin receptor (IR) substrate (IRS)-1, followed by reduced tyrosine
      phosphorylation of IRS-1 through the IR and, thereby, diminished IR signal
      transduction. Through independent receptor domains, TNF-R55 activates a neutral
      (N-SMase) and an acid sphingomyelinase (A-SMase), that both generate the
      sphingolipid ceramide. Multiple candidate kinases have been identified that
      serine-phosphorylate IRS-1 in response to TNF or ceramide. However, due to the
      fact that the receptor domain of TNF-R55 mediating inhibition of the IR has not
      been mapped, it is currently unknown whether TNF exerts these effects with
      participation of N-SMase or A-SMase. Here, we identify the death domain of TNF
      R55 as responsible for the inhibitory effects of TNF on tyrosine phosphorylation
      of IRS-1, implicating ceramide generated by A-SMase as a downstream mediator of
      inhibition of IR signaling.

PMID- 15721321
TI  - Role of a Ca2+-ATPase induced by ABA and IAA in the generation of specific Ca2+
      signals.
AB  - The control of the Ca(2+)-ATPase gene (LCA1) that encodes two different membrane
      located isoforms by two antagonic phytohormones, ABA and IAA, has been
      investigated. Strikingly both the growth regulators induce the LCA1 expression.
      By using a protoplast transient system, the cis-acting DNA elements responding to
      both, abiotic stress (ABA) and normal development (IAA), are dissected. ABA
      triggered a 4-fold increase in the GUS-activity. A single ACGT motif responsible
      for most of the LCA1 mRNA induction was localized at an unexpectedly large
      distance (1577 bp) upstream of the translational start. In the case of IAA,
      although there is a TGTCTC sequence that is known to be an important cis-acting
      element, two TGA motifs play a more critical role. It is proposed that the Ca(2+)
      ATPase isoforms might intervene in the generation of specific Ca(2+) signals by
      restoring steady-state Ca(2+) levels, modulating both frequency and amplitude of
      Ca(2+) waves via wave interference.

PMID- 15721322
TI  - Synthesis and antibacterial activity of mechanism-based inhibitors of KDO8P
      synthase and DAH7P synthase.
AB  - KDO8PS (3-deoxy-D-manno-2-octulosonate-8-phosphate synthase) and DAH7PS (3-deoxy
      D-arabino-2-heptulosonate-7-phosphate synthase) are attractive targets for the
      development of new anti-infectious agents. Both enzymes appear to proceed via a
      common mechanism involving the reaction of phosphoenolpyruvate (PEP) with
      arabinose 5-phosphate or erythrose-4-phosphate, to produce the corresponding
      ulosonic acids, KDO8P and DAH7P, respectively. The synthesis of new inhibitors
      closely related to the supposed tetrahedral intermediate substrates for the
      enzymes is described. The examination of the antibacterial activity of these
      derivatives is reported.

PMID- 15721324
TI  - Synthesis of new iso-C-nucleoside analogues from 2-(methyl 2-O-benzyl-4,6-O
      benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)ethanal.
AB  - Treatment of 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D
      altropyranosid-3-yl)ethanal with malononitrile, cyanoacetamide and 2-cyano-N-(4
      methoxyphenyl)acetamide, respectively, in the presence of aluminium oxide yielded
      2-cyano-4-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3
      yl)crotonic acid derivatives. Cyclization with sulfur and triethylamine was
      performed to synthesize the 2-amino-5-(methyl 2-O-benzyl-4,6-O-benzylidene-3
      deoxy-alpha-D-altropyranosid-3-yl)thiophene-3-carbonic acid derivatives, which
      were treated with triethyl orthoformate/ammonia and triethyl orthoformate,
      respectively, to furnish 6-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D
      altropyranosid-3-yl)thieno[2.3-d]pyrimidine derivatives. Deprotection in two
      steps afforded 2-amino-5-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thiophene
      3-carbonitrile and 6-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thieno[2.3
      d]pyrimidine derivatives, respectively.

PMID- 15721323
TI  - Synthesis of arabinitol 1-phosphate and its use for characterization of
      arabinitol-phosphate dehydrogenase.
AB  - D-arabinitol 1-phosphate (Ara-ol1-P), a substrate for D-arabinitol-phosphate
      dehydrogenase (APDH), was chemically synthesized from D-arabinonic acid in five
      steps (O-acetylation, chlorination, reduction, phosphorylation, and de-O
      acetylation). Ara-ol1-P was used as a substrate for the characterization of APDH
      from Bacillus halodurans. APDH converts Ara-ol1-P to xylulose 5-phosphate in the
      oxidative reaction; both NAD(+) and NADP(+) were accepted as co-factors. Kinetic
      parameters for the oxidative and reductive reactions are consistent with a
      ternary complex mechanism.

PMID- 15721325
TI  - Synthesis of glycosyl amino acids by light-induced coupling of photoreactive
      amino acids with glycosylamines and 1-C-aminomethyl glycosides.
AB  - The glycosylamines of O-acetyl-protected GlcNAc and chitobiose, as well as two
      partially unprotected 1-C-aminomethyl glucosides, were photochemically coupled
      with orthogonally protected N-aspartyl-5-bromo-7-nitroindoline derivatives. The
      reactions proceeded under neutral conditions by irradiation with near-UV light.
      The glycosyl asparagines with N- or C-glycosyl linkages were afforded in 60-85%
      yield on a 10-70 mg scale. Moreover, the ability of a highly photoreactive N
      glutamyl-4-methoxy-7-nitroindoline derivative to acylate amino saccharides was
      tested. Upon irradiation in the presence of a dimeric 1-C-aminomethyl glycoside,
      or a glycosylamine, the corresponding glycosyl glutamines were obtained in 50%
      and 30% yield, respectively. Preparations of the photoreactive aspartates and the
      1-C-aminomethyl glycosides are also described.

PMID- 15721326
TI  - Expeditious synthesis of enantiopure symmetrical macroheterocycles by ring
      closing metathesis of ether and tether-linked 1,2-O-isopropylidenefuranosides.
AB  - Bis-olefinic symmetrical carbohydrate derivatives were prepared by joining two
      1,2-O-isopropylidenefuranose units either through an ether linkage or by a tether
      of variable size. The ring-closing metathesis (RCM) of these substrates using
      Grubbs' first-generation catalyst led to the synthesis of enantiopure symmetrical
      macroheterocycles containing nine- to twenty-five-membered rings fused to the 1,2
      O-isopropylidenefuranose ring.

PMID- 15721327
TI  - Synthesis of new 2-C-(2,3:5,6-di-O-isopropylidene)-beta-D
      mannofuranosyldithioacetate derivatives.
AB  - Various new C-glycosides have been synthesized through the thioacylation reaction
      of different amines by a 2-C-mannofuranosyldithioacetate. Amino acids, di- and
      polyamines (putresceine, spermine, spermidine) and one amino alcohol were in
      particular used to generate glycothiopeptidic or precursors of "bola" structures.

PMID- 15721328
TI  - Convenient preparation of 3,5-anhydro- and 2,5-anhydropentofuranosides, and 5,6
      anhydro-D-glucofuranose by use of the Mitsunobu reaction.
AB  - Methyl 3,5-anhydro-alpha-D-xylofuranosides are obtained by use of the Mitsunobu
      reaction from 2-O-protected methyl alpha-D-xylofuranosides, which are easily
      prepared from D-xylose. The Mitsunobu reaction of methyl 3-N-benzylamino-3-deoxy-
      and 3-azido-3-deoxyarabinofuranosides, which are prepared from the conveniently
      available methyl 2,3-anhydro-alpha-D- and 2,3-anhydro-alpha-l-lyxofuranosides by
      nucleophilic ring opening, yields the corresponding methyl 2,5-anhydro-alpha-D-
      and 2,5-anhydro-alpha-l-arabinofuranosides. Ring opening of 3,5-anhydro-1,2-O
      isopropylidene-alpha-D-xylofuranose with azide yields the corresponding 5-azido
      derivative. The structure and configuration of the products is confirmed by NMR
      spectroscopy. 5,6-Anhydro-1,2-O-isopropylidene-alpha-D-glucofuranose is formed by
      the Mitsunobu reaction of 1,2-O-isopropylidene-alpha-D-glucofuranose. Its
      structure is verified by single-crystal X-ray diffraction analysis.

PMID- 15721329
TI  - Synthesis of galactose-containing analogues of (1-->6)-branched (1-->3)
      glucohexaose and its lauryl glycoside.
AB  - Coupling of the trisaccharide acceptor either 2,4,6-tri-O-acetyl-beta-D
      glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-5
      O-acetyl-1,2-O-isopropylidene-alpha-D-glucofuranose (13) or lauryl 2,4,6-tri-O
      acetyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D
      glucopyranosyl-(1-->6)]-2,5-di-O-acetyl-alpha-D-glucopyranoside (15) with the
      trisaccharide donor 2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->3)
      [2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D
      galactopyranosyl trichloroacetimidate (12) gave alpha-linked hexasaccharides 14
      and 16, respectively, while coupling of either 13 or 15 with trisaccharide donor
      2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl
      beta-D-galactopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-galactopyranosyl
      trichloroacetimidate 17 did not afford any hexasaccarides. The analogues of the
      immunomodulator beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-alpha-D-Glcp-(1-->3)
      beta-D-Glcp-beta-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp (1) was obtained by
      deprotection of 14 and 16.

PMID- 15721330
TI  - Synthesis of (R)-2,3-epoxypropyl(1-->3)-beta-D-pentaglucoside.
AB  - The title pentasaccharide was synthesized via a 2+3 strategy. The disaccharide
      donor, 3-O-acetyl-2-O-benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O
      benzoyl-4,6-O-benzylidene-alpha-D-glucopyranosyl trichloroacetimidate (8), was
      obtained by selective coupling of allyl 2-O-benzoyl-4,6-O-benzylidene-alpha-D
      glucopyranoside with 3-O-acetyl-2-O-benzoyl-4,6-O-benzylidene-alpha-D
      glucopyranosyl trichloroacetimidate (4), followed by deallylation, and
      trichloroacetimidation. Meanwhile, the trisaccharide acceptor, allyl 2-O-benzoyl
      4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene
      beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D
      glucopyranoside (12), was prepared by coupling of allyl 2-O-benzoyl-4,6-O
      benzylidene-beta-D-glucopyranosyl-(1-->3)-2-O-benzoyl-4,6-O-benzylidene-beta-D
      glucopyranoside with 4, followed by deacetylation. Condensation of 8 with 12,
      followed by epoxidation, and deprotection, gave the target pentaoside.

PMID- 15721331
TI  - The production, purification and characterisation of two novel alpha-D
      mannosidases from Aspergillus phoenicis.
AB  - 1,6-alpha-D-Mannosidase from Aspergillus phoenicis was purified by anion-exchange
      chromatography, chromatofocussing and size-exclusion chromatography. The apparent
      molecular weight was 74 kDa by SDS-PAGE and 81 kDa by native-PAGE. The
      isoelectric point was 4.6. 1,6-alpha-D-Mannosidase had a temperature optimum of
      60 degrees C, a pH optimum of 4.0-4.5, a K(m) of 14 mM with alpha-D-Manp-(1-->6)
      D-Manp as substrate. It was strongly inhibited by Mn(2+) and did not need Ca(2+)
      or any other metal cofactor of those tested. The enzyme cleaves specifically (1-
      >6)-linked mannobiose and has no activity towards any other linkages, p
      nitrophenyl-alpha-D-mannopyranoside or baker's yeast mannan. 1,3(1,6)-alpha-D
      Mannosidase from A. phoenicis was purified by anion-exchange chromatography,
      chromatofocussing and size-exclusion chromatography. The apparent molecular
      weight was 97 kDa by SDS-PAGE and 110 kDa by native-PAGE. The 1,3(1,6)-alpha-D
      mannosidase enzyme existed as two charge isomers or isoforms. The isoelectric
      points of these were 4.3 and 4.8 by isoelectric focussing. It cleaves alpha-D
      Manp-(1-->3)-D-Manp 10 times faster than alpha-D-Manp-(1-->6)-D-Manp, has very
      low activity towards p-nitrophenyl-alpha-D-mannopyranoside and baker's yeast
      mannan, and no activity towards alpha-D-Manp-(1-->2)-D-Manp. The activity towards
      (1-->3)-linked mannobiose is strongly activated by 1mM Ca(2+) and inhibited by
      10mM EDTA, while (1-->6)-activity is unaffected, indicating that the two
      activities may be associated with different polypeptides. It is also possible
      that one polypeptide may have two active sites catalysing distinct activities.

PMID- 15721332
TI  - An alpha-glucan elicitor from the cell wall of a biocontrol binucleate
      Rhizoctonia isolate.
AB  - Binucleate Rhizoctonia (BNR) isolate (232-C6) is an effective biocontrol agent
      for protection of potato from Rhizoctonia canker, a disease caused by Rhizoctonia
      solani. Production of hydrolytic enzymes is one of the best known inducible
      defense responses following microbial infection. We isolated and characterized a
      cell wall alpha-glucan from BNR, which induces beta-1,3 glucanase activities in
      potato sprouts, the primary site of infection by R. solani. An autoclaving
      method, previously reported for isolation of oligosaccharide elicitors was used,
      and the glucan purified by chromatographic techniques. Maximal induction of beta
      1,3 glucanase activity in potato sprouts was obtained with 250 microg of the
      alpha-glucan elicitor after 6 days from inoculation time. Both, BNR mycelium and
      the alpha-glucan produced a similar kinetic response of beta-1,3 glucanase.
      However, the alpha-glucan did not induce phytoalexin accumulation, previously
      correlated with the defense response. Uronic acids (approximately 10% with
      respect to total neutral sugars) were determined and identified as glucuronic
      acid by high-pH anion-exchange chromatography. Methylation analysis showed that
      the glucan consists of (1-->3) and (1-->4)-linked glucose units with
      preponderance of the first ones. Some of the (1-->4) linkages were branched at
      position 6. The glucan was partially degraded with amyloglucosidase. This,
      together with the NMR spectra data and the high optical rotation of the original
      (+195 degrees ) and degraded glucans (+175 degrees ) proved the alpha
      configuration. Further methylation of the amyloglucosidase degraded glucans
      indicated that they consist of (1-->3)-linked glucoses. The present study is the
      first report on the isolation and characterization of an alpha-glucan from
      Rhizoctonia, that may be important as a biocontrol factor.

PMID- 15721333
TI  - Structural investigation of a polysaccharide (Fr. II) isolated from the aqueous
      extract of an edible mushroom, Pleurotus sajor-caju.
AB  - A water-soluble polysaccharide, (Fr. II) isolated from aqueous extract of an
      edible mushroom Pleurotus sajor-caju, was found to consist of D-glucose, D
      galactose, and D-mannose in a molar proportion of 1:1:1. Compositional analysis,
      methylation analysis, periodate oxidation study, partial hydrolysis, and NMR
      experiments ((1)H, (13)C, 2D-COSY, TOCSY, NOESY, HSQC, and HMBC) revealed the
      presence of the following repeating unit in the polysaccharide: [formula: see
      text]

PMID- 15721334
TI  - An original chemoenzymatic route for the synthesis of beta-D-galactofuranosides
      using an alpha-L-arabinofuranosidase.
AB  - DGalactofuranose is a widespread component of cell wall polysaccharides in
      bacteria, protozoa and fungi, but is totally absent in mammals. Importantly,
      galactofuranose is a key constituent of major cell envelope polysaccharides in
      pathogenic mycobacteria. In this respect, galactofuranose-based glycoconjugates
      are interesting target molecules for drug design. O-Glycosidases and notably beta
      D-galactofuranosidases could be useful tools for the chemoenzymatic synthesis of
      galactofuranosides, but to date no studies of this type have been reported. Here
      we report the use of a GH 51 alpha-l-arabinofuranosidase for the synthesis of
      beta-D-galactofuranosides. We have demonstrated that this enzyme can catalyse
      both the autocondensation of p-nitrophenyl-beta-D-galactofuranoside and the
      transgalactofuranosylation of benzyl alpha-D-xylopyranoside, forming p
      nitrophenyl beta-D-galactofuranosyl-(1-->2)-beta-D-galactofuranoside and benzyl
      beta-D-galactofuranosyl-(1-->2)-alpha-D-xylopyranoside, respectively. Both
      reactions were very regiospecific and the reaction involving benzyl alpha-D
      xylopyranoside afforded very high yields (74.8%) of the major product. To our
      knowledge, this demonstration of chemoenzymatic synthesis of galactofuranosides
      constitutes the very first use of an O-glycosidase for the synthesis of
      galactofuranosides.

PMID- 15721335
TI  - Structural elucidation of the O-antigenic polysaccharide from the
      enteroaggregative Escherichia coli strain 180/C3 and its immunochemical
      relationship with E. coli O5 and O65.
AB  - The structure of the O-antigen polysaccharide (PS) from the enteroaggregative
      Escherichia coli strain 180/C3 has been determined. Sugar and methylation
      analysis together with (1)H and (13)C NMR spectroscopy were the main methods
      used. The PS is composed of tetrasaccharide repeating units with the following
      structure: -->2)beta-D-Quip3NAc-(1-->3)beta-D-RIBf-(1-->4)beta-D-Galp-(1-
      >3)alpha-D-GalpNAc-(1-->. Analysis of NMR data indicates that the presented
      sequence of sugar residues also represents the biological repeating unit of the O
      chain. The structure is closely related to that of O-antigen polysaccharide from
      E. coli O5 and partially to that of E. coli O65. The difference between the O
      antigen from the 180/C3 strain and that of E. coli O5 is the linkage to the D
      Quip3NAc residue, which in the latter strain is 4-O-substituted. The E. coli O65
      O-antigen contains as part of its linear pentasaccharide repeating unit a similar
      structural element, namely -->4)-beta-d-GalpA-(1-->3)-alpha-D-GlcpNAc-(1-->2)
      beta-D-Quip3NAc-(1-->, thereby indicating that a common epitope could be present
      for the two polysaccharides. Monospecific anti-E. coli O5 rabbit serum did not
      distinguish between the two positional isomeric structures neither in slide
      agglutination nor in an indirect enzyme immunoassay. The anti-O65 serum did react
      with both the 180/C3 and O5 LPS showing a partial cross-reactivity.

PMID- 15721336
TI  - The structure of the O-polysaccharide from Pseudomonas stutzeri OX1 containing
      two different 4-acylamido-4,6-dideoxy-residues, tomosamine and perosamine.
AB  - The structure of the O-polysaccharide from the lipopolysaccharide of Pseudomonas
      stutzeri OX1 was determined by chemical procedures and by 1D and 2D NMR
      spectroscopy. The analysis revealed the presence of a heterogeneous polymer made
      by 4-acetamido-4,6-dideoxy-D-mannopyranose (D-Rhap4NAc) and 4-formamido-4,6
      dideoxy-D-galactopyranose (d-Fucp4NFo). The combination of chemical and NMR
      analyses indicates that the heterogeneity of the polymer depends on its non
      stoichiometric glycosylation by Fuc4NFo, as shown below: [formula: see text]. The
      structure of the heterogeneous polymer was confirmed by Smith degradation that
      significantly simplified the structure of the O-polysaccharide, allowing for the
      isolation and identification of a linear homopolymer of Rhap4NAc.

PMID- 15721337
TI  - Structural and immunological properties of arabinogalactan polysaccharides from
      pollen of timothy grass (Phleum pratense L.).
AB  - Extracts from pollen of timothy grass (Phleum pratense L.) contain up to 20%
      arabinogalactan proteins (AGPs). Separation of the AGP polysaccharide moieties by
      tryptic digestion, size exclusion chromatography (GPC), and reverse phase HPLC
      yielded arabinogalactan fractions AG-1 and AG-2 with molecular weights of
      approximately 15,000 and approximately 60,000Da, respectively. The backbones of
      both polysaccharides are composed of (1-->6)-linked beta-D-galactopyranosides
      with beta-D-GlcUAp or 4-O-Me-beta-D-GlcUAp at their terminal ends as revealed by
      chemical analysis, FT-IR, MALDI-MS, and NMR spectroscopy. AG-1 contains a small
      number of beta-l-Araf side chains while AG-2 possesses a variety of (1-->3)
      linked units, which consist of beta-l-Araf-(1-->, alpha-l-Araf-(1-->3)-beta-l
      Araf-(1-->, and alpha-l-Araf-(1-->5)-beta-l-Araf-(1--> as well as a small number
      of longer arabinogalactan side chains. In contrast to crude pollen extracts, the
      immunological properties of the arabinogalactan mixture reveal an IgG4 reactivity
      instead of IgE reactivity. Structural properties of timothy pollen
      arabinogalactan might thus influence the immune response.

PMID- 15721338
TI  - Structural analysis of the oligosaccharide of Histophilus somni (Haemophilus
      somnus) strain 2336 and identification of several lipooligosaccharide
      biosynthesis gene homologues.
AB  - The structure of the core oligosaccharide from a pneumonic Histophilus somni
      (Haemophilus somnus) strain 2336 was elucidated. The lipooligosaccharide (LOS)
      was subjected to a variety of degradative procedures. The structures of the
      purified products were established by monosaccharide and methylation analyses,
      NMR spectroscopy and mass spectrometry. The following structure for the core
      oligosaccharide was determined on the basis of the combined data from these
      experiments: [formula-see text]. The structural elucidation was intriguing as it
      suggested several differences in the LOS structures between strain 2336 and the
      related strain 738. Strain 738 originated following passaging of strain 2336
      through a calf. The differences between the two structures are a different
      linkage between Gal II and GlcNAc (1-->4 here; 1-->3 in 738), the absence of
      phosphocholine (PCho) from 2336 and the presence of two phosphoethanolamine
      (PEtn) residues and Gal III (at the 2-position) of Hep II in 2336. Although pulse
      field gel electrophoresis data following digest with only one restriction enzyme
      showed identical profiles suggesting that strains 738 and 2336 are the same
      strain, the structural data does suggest that, if strain 738 is indeed a phase
      variant of strain 2336, considerable variation occurred on calf passaging and
      could therefore be an intriguing example of how broadly this bacterium can adapt
      itself in the host.

PMID- 15721339
TI  - Structural analyses of novel glycerophosphorylated alpha-cyclosophorohexadecaoses
      isolated from X. campestris pv. campestris.
AB  - Novel periplasmic anionic cyclic glucans produced by Xanthomonas campestris pv.
      campestris were isolated by trichloroacetic acid treatment and various
      chromatographic techniques. No report has been made on the presence of
      substituted cyclic glucans of the Xanthomonas species. We show, for the first
      time, that X. campestris pv. campestris produces the anionic cyclic glucans with
      phosphoglycerol residues, the presence of which can be predicted by analyzing the
      sequence database with the aid of the NCBI RefSeq database. To analyze the
      structure of isolated anionic cyclic glucans analyses, we used NMR spectroscopy,
      matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      (MALDI-TOFMS) and electrospray-ionization mass spectrometry (ESIMS). The results
      suggest that the novel anionic forms of the cyclic glucans of X. campestris pv.
      campestris are glycerophosphorylated alpha-cyclosophorohexadecaose with one or
      two phosphoglycerol substituents at the C-6 positions of the glucose residues.

PMID- 15721340
TI  - Periodate oxidation of chitosans with different chemical compositions.
AB  - Periodate oxidation of chitosans with different chemical compositions were
      investigated by determining the consumption of periodate consumed, and the amount
      of ammonia and formaldehyde liberated during the reaction. Oxidised chitosans
      were further characterised by size-exclusion chromatography with online multi
      angle light scattering (SEC-MALLS) to obtain the molecular weight distributions,
      and by elemental analysis to obtain the N/C ratio. Chitosans became only
      partially oxidised by periodate, reaching degrees of oxidation around 0.5, when
      oxidising with excess periodate. Overconsumption of periodate is attributed to
      the extensive depolymerisation, which occurs concomitantly with the oxidation,
      thereby exposing novel reducing and non-reducing ends which consume additional
      periodate. Both the rate and extent of overoxidation, and the rate of
      depolymerisation decreased with increasing F(A). A chitosan-specific degradation
      mechanism is probably involved in the depolymerisation in addition to the general
      free-radical-mediated degradation.

PMID- 15721341
TI  - Preparation and in vitro antioxidant activity of kappa-carrageenan
      oligosaccharides and their oversulfated, acetylated, and phosphorylated
      derivatives.
AB  - In order to study the relationship between chemical structure and properties of
      modified carrageenans versus antioxidant activity in vitro, kappa-carrageenan
      oligosaccharides were prepared through mild hydrochloric acid hydrolysis of the
      polysaccharide, and these were used as starting materials for the partial
      synthesis of their oversulfated, acetylated, and phosphorylated derivatives. The
      structure and substitution pattern of the oligosaccharides and their derivatives
      were studied using FTIR and (13)C NMR spectroscopy, and their in vitro
      antioxidant activities were investigated. Certain derivatives of the carrageenan
      oligosaccharides exhibited higher antioxidant activity than the polysaccharides
      and oligosaccharides in certain antioxidant systems. The oversulfated and
      acetylated derivatives, which scavenge superoxide radicals, the phosphorylated
      and low-DS acetylated derivatives, which scavenge hydroxyl radicals, and the
      phosphorylated derivatives, which scavenge DPPH radicals, all exhibited
      significant antioxidant activities in the systems examined. The effect of the
      molecular weight of the carrageenan on antioxidant activities, however, is not
      obvious from these studies.

PMID- 15721342
TI  - Structural and serological characterization of the O-chain polysaccharide of
      Aeromonas salmonicida strains A449, 80204 and 80204-1.
AB  - The O-chain polysaccharide (O-PS) of Aeromonas salmonicida was studied by a
      combination of compositional, methylation, CE-ESMS and one- and two-dimensional
      NMR analyses. It was found to be a branched polymer of trisaccharide-repeating
      units composed of L-rhamnose (Rha), D-glucose (Glc), 2-acetamido-2-deoxy-D
      mannose (ManNAc) and O-acetyl group (OAc) and having the following structure: CE
      ESMS analysis of A. salmonicida cells from strains A449, 80204 and 80204-1 grown
      under different conditions confirmed that the O-PS structure was conserved. ELISA
      based serological study with native LPS-specific antisera performed on the native
      O-PS and its O-deacetylated and periodate-oxidized derivatives confirmed the
      importance of the O-PS backbone structure as an immunodominant determinant.

PMID- 15721344
TI  - The system of galactans from Cryptonemia crenulata (Halymeniaceae, Halymeniales)
      and the structure of two major fractions. Kinetic studies on the alkaline
      cyclization of the unusual diad G2S-->D(L)6S.
AB  - Cryptonemia crenulata biosynthesizes a family of dl-hybrid galactans that are
      based on the classical 3-linked beta-d-galactopyranosyl-->4-linked alpha
      galactopyranosyl alternating sequence (A-units-->B-units). The dispersion of
      structures in these galactans is based on four factors, namely: (a) the amount
      and position of substituent groups as sulfate (major), pyruvic acid ketals,
      methoxyl and side substituents of beta-D-xylose and/or beta-D-galactose; (b) the
      ratio galactose/3,6-anhydrogalactose in the B-units; (c) the ratio D-/L
      galactoses and 3,6-anhydrogalactoses also in the B-units and (d) the sequence of
      the diads in the linear backbone. Alkali treatment carried out on the major
      fraction produced a nearly quantitative formation of 3,6-anhydrogalactose units
      from precursor units (alpha-galactose 6-sulfate (major) and alpha-galactose 2,6
      sulfate, minor). Kinetic studies show a rate constant, for the diad G2S-D(L) 6-S,
      of 1.7 x 10(4)s(-1) indicating a reaction faster than in lambda-carrageenans but
      slower than in porphyrans.

PMID- 15721343
TI  - High-performance size-exclusion chromatography (HPSEC) and fluorophore-assisted
      carbohydrate electrophoresis (FACE) to describe the chain-length distribution of
      debranched starch.
AB  - Chain-length (CL) distribution is an important feature of the "fine structure" of
      starch molecules, which are comprised of amylose and amylopectin. The objective
      of the present work was to combine data for two methods to achieve a more
      comprehensive data set that would allow a fuller comparison of the CL
      distribution for different starches. Both high-performance size-exclusion
      chromatography (HPSEC) and fluorophore-assisted carbohydrate electrophoresis
      (FACE) were carried out on endosperm starch isolated from five maize genotypes.
      For the CL distribution in the range DP50, data in the HPSEC chromatogram were
      transformed to the form of a FACE electrophoregram, in which the x-axis is DP and
      the y-axis is the number of chains. The two sets of data in this region were
      shown to be similar. We conclude that the data sets from HPSEC and FACE may be
      considered together to describe the CL distribution more completely than for
      either method alone. We further note that for DP 6-50, data from HPSEC may be
      transformed to allow a similar presentation as for that obtained by FACE, such
      that FACE analysis might not be required for comparison of CL distribution of
      different starches.

PMID- 15721345
TI  - 13C solid-state NMR chemical shift anisotropy analysis of the anomeric carbon in
      carbohydrates.
AB  - (13)C NMR solid-state structural analysis of the anomeric center in carbohydrates
      was performed on six monosaccharides: glucose (Glc), mannose (Man), galactose
      (Gal), galactosamine hydrochloride (GalN), glucosamine hydrochloride (GlcN), and
      N-acetyl-glucosamine (GlcNAc). In the 1D (13)C cross-polarization/magic-angle
      spinning (CP/MAS) spectrum, the anomeric center C-1 of these carbohydrates
      revealed two well resolved resonances shifted by 3-5ppm, which were readily
      assigned to the anomeric alpha and beta forms. From this experiment, we also
      extracted the (13)C chemical shift anisotropy (CSA) tensor elements of the two
      forms from their spinning sideband intensities, respectively. It was found out
      that the chemical shift tensor for the alpha anomer was more axially symmetrical
      than that of the beta form. A strong linear correlation was obtained when the
      ratio of the axial asymmetry of the (13)C chemical shift tensors of the two
      anomeric forms was plotted in a semilogarithmic plot against the relative
      population of the two anomers. Finally, we applied REDOR spectroscopy to discern
      whether or not there were any differences in the sugar ring conformation between
      the anomers. Identical two-bond distances of 2.57A (2.48A) were deduced for both
      the alpha and beta forms in GlcNAc (GlcN), suggesting that the two anomers have
      essentially identical sugar ring scaffolds in these sugars. In light of these
      REDOR distance measurements and the strong correlation observed between the ratio
      of the axial asymmetry parameters of the (13)C chemical shift tensors and the
      relative population between the two anomeric forms, we concluded that the
      anomeric effect arises principally from interaction of the electron charge clouds
      between the C-1-O-5 and the C-1-O-1 bonds in these monosaccharides.

PMID- 15721346
TI  - Rapid synthesis of partially O-methylated alditol acetate standards for GC-MS:
      some relative activities of hydroxyl groups of methyl glycopyranosides on Purdie
      methylation.
AB  - Mixtures containing the majority of partially O-methylated alditol acetates
      (PMAAs), necessary for the GC-MS based identification of glycosidic linkages in
      oligo- and polymeric structures were prepared. Rha, Fuc, Rib, Ara, Xyl, Man, Gal,
      and Glc were converted to their Me glycosides, and the products were
      progressively O-methylated using the Purdie reagent at 25 degrees C. Resulting
      PMGs were assayed by TLC and at times that were optimum for formation of mono-O
      methyl derivatives and later for higher degrees of methylation; they were
      converted to PMAAs, in a process incorporating NaB(2)H(4) reduction. The majority
      of these can be used as standards for simultaneous identification of pyranosides
      and some furanosyl units particularly in heteropolysaccharides. The relative
      reactivities of OH-groups were determined by GC-MS as: Me alpha- and beta-Glcp,
      HO-2>HO-4>HO-3>HO-6, Me alpha- and beta-Galp, HO-3>HO-2>HO-4>HO-6, Me alpha-Manp,
      HO-3>HO-2>HO-4>HO-6, Me beta-Manp, HO-3>HO-4HO-6>HO-2, Me alpha-Rhap, OH-3>OH
      2>OH-4; Me alphabeta-Fucp, OH-2>OH-3>OH-4, and Me alphabeta-Xylp, OH-2>OH-4>OH-3.
      The results differ from those obtained with Haworth, Hakomori, and Ciucanu
      methylation techniques, although some similarities occurred with the more rapid
      Kuhn method.

PMID- 15721347
TI  - Concentrated hydriodic acid in simultaneous deprotections of multifunctional
      inositols.
AB  - l-1-Deoxy-1-fluoro-6-O-methyl-myo-inositol was epimerized by chloral/DCC in
      boiling 1,2-dichloroethane yielding D-1-O-cyclohexylcarbamoyl-2-deoxy-2-fluoro-3
      O-methyl-5,6-O-[(R/S)-2,2,2-trichloroethylidene]-chiro-inositol. The latter and l
      4-O-benzyl-3-O-cyclohexylcarbamoyl-5-O-methyl-1,2-O-(2,2,2-trichloroethylidene)
      muco-inositol, l-4-O-benzyl-3-O-cyclohexylcarbamoyl-1,2-O-ethylidene-5-O-methyl
      muco-inositol, d-1-O-cyclohexylcarbamoyl-2-deoxy-5,6-O-ethylidene-2-fluoro-3-O
      methyl-chiro-inositol, as well as D-5-O-benzyl-4-O-cyclohexylcarbamoyl-3-deoxy-3
      (N,N'-dicyclohexylureido)-6-O-methyl-1,2-O-(2,2,2-trichloroethylidene)-chiro
      inositol were deprotected with boiling 57% aq hydrogen iodide. Ether, urethane
      and ethylidene acetal functions were simultaneously cleaved by the reagent,
      whereas the trichloroethylidene groups were still intact or were only removed in
      small quantities. Especially, the urea function of D-5-O-benzyl-4-O
      cyclohexylcarbamoyl-3-deoxy-3-(N,N'-dicyclohexylureido)-6-O-methyl-1,2-O-(2,2,2
      trichloroethylidene)-chiro-inositol was decomposed to a cyclohexylamino group.
      The hydrodechlorination of D-1-O-cyclohexylcarbamoyl-2-deoxy-2-fluoro-3-O-methyl
      5,6-O-[(R/S)-2,2,2-trichloroethylidene]-chiro-inositol using Raney-Nickel yielded
      a mixture of the corresponding 5,6-O-ethylidene- and 5,6-O-chloroethylidene
      derivatives. The three synthetic steps-hydrodehalogenation, HI-deprotection and
      peracylation- were combined without purification of the intermediates.

PMID- 15721348
TI  - Synthesis of 2,3-unsaturated C-glycosides by HClO4-SiO2 catalyzed Ferrier
      rearrangement of glycals.
AB  - Alkyl 2,3-unsaturated C-glycopyranosides have been prepared by Ferrier
      rearrangement of acyl or alkyl protected glycals catalyzed by HClO(4)-SiO(2).

PMID- 15721349
TI  - Stereoselective synthesis of a ketohexofuranose from an aldohexopyranose by a
      [6+1-1] strategy.
AB  - Ozonolysis of 2-acetoxymethyl-1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-D-arabino
      hex-1-enitol gave 1-O-acetyl-3,4,6-tri-O-benzyl-4-O-formyl-D-arabino-hex-2-ulose
      (5). Subsequent hydrolysis and acetylation of 5 provided 1,2-di-O-acetyl-3,4,6
      tri-O-benzyl-D-fructofuranose 6 in excellent yield. This methodology allows
      specific deuteration at C-1 of a protected D-fructofuranose derivative. This
      approach therefore could serve as [6+1-1] formulation for hexose series inter
      conversion, that is, aldohexopyranose to ketohexofuranose.

PMID- 15721350
TI  - Sepharose-bound, highly sulfated glycosaminoglycans can capture HIV-1 from
      culture medium.
AB  - In the search for new strategies against HIV-1 and on the basis of a number of
      previous studies reporting on the capacity of certain polyanionic compounds to
      influence the replication of HIV-1, we prepared a few chemically oversulfated
      dermatan and chondroitin sulfates. Four of these compounds and two samples of
      heparin were bound to activated Sepharose through either their carboxylic groups,
      or their aldehydic groups, or their deacetylated primary amino groups. Some of
      these so-derivatised resins, packed into columns, proved able to remove HIV-1
      IIIB, a laboratory adapted strain, and one clinical primary isolate from an AIDS
      patient, from infected cell culture medium. The resins bind the virus very
      tightly and could be useful for capturing the virus from infected fluids.

PMID- 15721351
TI  - Identification of a capsular polysaccharide from Moraxella bovis.
AB  - The bacterium Moraxella bovis is the causative agent of an economically important
      disease of cattle: Infectious Bovine Keratoconjunctivitis (IBK), otherwise known
      as pinkeye. Little is known regarding the structure of the carbohydrates produced
      by M. bovis. The structure of a capsular polysaccharide from M. bovis (strain
      Mb25) has been determined using NMR and MS analysis. From these data it is
      concluded that the polysaccharide is composed of the unmodified chondroitin
      disaccharide repeat unit.

PMID- 15721352
TI  - Further evidence of the changing nature of biopolymer networks in the presence of
      sugar.
AB  - Despite claims made in the literature that polysaccharides maintain a
      substantially aggregated morphology in the form of "gel particulates" or "gel
      islands" at a high sugar environment, results of differential scanning
      calorimetry (DSC) discussed now demonstrate that extensive macromolecular order
      is not thermodynamically stable. Gelatin, on the other hand, appears to demix
      from the sugar-rich domains, which promote chain association rather than
      inhibiting it. DSC evidence is supported by previously published transmission
      electron microscopy (TEM) work and mechanical analysis.

PMID- 15721353
TI  - The structure of the O-polysaccharide from the lipopolysaccharide of Providencia
      stuartii O57 containing an amide of D-galacturonic acid with L-alanine.
AB  - The O-polysaccharide (O-antigen) was obtained by mild acid degradation of the
      lipopolysaccharide of Providencia stuartii O57:H29. Studies by sugar and
      methylation analyses along with (1)H and (13)C NMR spectroscopy, including two
      dimensional (1)H,(1)H COSY, TOCSY, ROESY, H-detected (1)H,(13)C HSQC, and HMBC
      experiments, showed that the polysaccharide contains an amide of D-galacturonic
      acid with L-alanine and has the following pentasaccharide repeating unit:
      [formula: see text]

PMID- 15721355
TI  - Use of chimeric adenoviral vectors to assess capsid neutralization determinants.
AB  - In order to elucidate the relative importance of neutralizing determinants on
      each of the three major adenoviral capsid components, we have generated chimeric
      vectors where the hexon protein, or the fiber protein, or both hexon and fiber
      proteins of one serotype (Simian Adenovirus 24/Pan 7) have been replaced by those
      of another (Simian Adenovirus 23/Pan 6). The effect of each replacement was
      evaluated by neutralization assays and by attempted vector re-administration into
      mice. Both hexon and fiber were found to harbor neutralization epitopes although
      in vivo transduction was more severely affected by anti-hexon antibodies.

PMID- 15721354
TI  - Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2
      activity.
AB  - Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell
      proliferative diseases such as Burkitt's lymphoma. Here we show that the
      oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the
      viral transcriptional activator EBNA2. During EBV infection of primary B
      lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are
      upregulated and remain elevated in latently infected B-cell lines. Thus, EBV
      induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional
      activity may contribute to the ability of EBV to immortalize B-cells and
      predispose them to malignant growth.

PMID- 15721357
TI  - Kinetics of expansion of SIV Gag-specific CD8+ T lymphocytes following challenge
      of vaccinated macaques.
AB  - The ability of memory T cells to mount a recall response plays a key role in the
      ability of vaccinated animals to contain viral challenge. In this study, we
      intensively monitored the expansion of SIV Gag-specific CD8+ T cells in
      peripheral blood and tissues of rhesus macaques vaccinated with the attenuated
      strain SIVmac239Delta3 and challenged with the pathogenic viruses SIVmac239 or
      SIVsmE660. Although all vaccinated animals were infected with challenge virus,
      peak levels of plasma viremia in vaccinees were decreased by 1.5 to 2 logs as
      compared with naive controls. Decreased levels of plasma viremia in vaccinated
      animals were evident as early as 7 days post-challenge, well before the expansion
      of SIV-specific CD8+ T cells. Expansion of SIV-specific CD8+ T cells was not
      observed in peripheral blood or tissues until at least 14 days after infection
      and did not occur in most animals until after the initial peak of viral
      replication. The observation that expansion of SIV-specific CD8+ T cells is
      delayed until 7 days or more after initial detection of viremia highlights
      fundamental limitations in the ability of lentivirus-specific CD8+ T cells to
      mediate protection against challenge.

PMID- 15721356
TI  - VSV replication in neurons is inhibited by type I IFN at multiple stages of
      infection.
AB  - Vesicular stomatitis virus (VSV) is a rhabdovirus which causes acute encephalitis
      in mice after intranasal infection. Because type I interferon (IFN) has been
      shown to be a potent inhibitor of VSV, we investigated the role of type I IFN in
      viral replication in neurons in culture. Pre-treatment of NB41A3 neuroblastoma
      cells or primary neuron cultures with IFN-beta or IFN-alpha strongly inhibits
      virus replication, with 1000-fold inhibition of infectious virus release
      occurring at 7 h post-infection, and maximum inhibition of 14,000-fold occurring
      at 14 h. Type I IFN inhibited both viral protein and RNA synthesis, but not
      enough to account for the inhibition of infectious virus yield. The influenza
      virus protein NS1 binds dsRNA and antagonizes induction of PKR activity, an IFN
      inducible antiviral protein which phosphorylates and inactivates the elongation
      factor eIF-2alpha, resulting in cessation of translation. In NS1-expressing
      neuroblastoma cells, VSV replication was inhibited by IFN-beta as well as in
      control NB41A3 cells, and eIF-2alpha phosphorylation was blocked, suggesting that
      PKR activity was not involved in inhibition of viral protein synthesis.
      Similarly, inhibition of VSV by IFN-beta was not affected by addition of
      inhibitors of nitric oxide synthase, indicating that IFN-beta activity is not
      mediated by nitric oxide or superoxide. This contrasts with the essential role of
      NOS-1 in inhibition of VSV replication when neurons are treated with IFN-gamma.
      Analysis of cell culture supernatants revealed suppression of release of VSV
      particles from both NB41A3 cells and primary neurons treated with IFN. The
      inhibition of virion release closely matched the overall suppression of
      infectious VSV particle release, suggesting that type I IFN plays a role in
      inhibition of VSV assembly.

PMID- 15721358
TI  - Secretion of noninfectious dengue virus-like particles and identification of
      amino acids in the stem region involved in intracellular retention of envelope
      protein.
AB  - DNA plasmids that express flavivirus premembrane/membrane (prM/M) and envelope
      (E) proteins in the form of virus-like particles (VLPs) have an excellent
      potential as DNA vaccine candidates against virus infection. The plasmid
      expressed VLPs are also useful as safe, noninfectious antigens in serodiagnostic
      assays. We have constructed plasmids containing the prM/M and E gene regions for
      DENV-1, -3, and -4 that express and secrete VLPs when electroporated into Chinese
      hamster ovary cells. Constructs containing the full-length DENV-1 E protein gene
      did not secrete VLPs into tissue culture fluid effectively. However, a 16-fold
      increase in ELISA titers of DENV-1 VLPs was achieved after replacing the carboxy
      terminal 20% region of DENV-1 E protein gene with the corresponding sequence of
      Japanese encephalitis virus (JEV). DENV-3 plasmids containing either the full
      length DENV-3 E protein gene or the 20% JEV sequence replacement secreted VLPs to
      similarly high levels. Whereas DENV-4 VLPs were secreted to high levels by
      plasmids containing the full-length DENV-4 E protein gene but not by the chimeric
      plasmid containing 20% JEV E replacement. Domain substitutions by replacing prM/M
      protein stem-anchor region with the corresponding prM/M stem-anchor region of JEV
      or DENV-2 in the chimeric DENV-4 construct failed to promote the secretion of
      DENV-4 VLPs. Using the DENV-2 chimeric plasmid with carboxy-terminal 10% of JEV E
      gene, the sequence responsible for intracellular localization of E protein was
      mapped onto the E-H1 alpha-helix domain of DENV-2 E protein. Substitution of
      three amino acids from the DENV-2 sequence to the corresponding amino acids in
      the JEV sequence (I398L, M401A, and M412L) in the E-H1 was sufficient to promote
      extracellular secretion and resulted in detectable titers of DENV-2 VLP
      secretion.

PMID- 15721359
TI  - T20-insensitive HIV-1 from naive patients exhibits high viral fitness in a novel
      dual-color competition assay on primary cells.
AB  - The relationship between sensitivity to antiviral drugs and viral fitness is of
      paramount importance in understanding the long-term implications of clinical
      resistance. Here we report the development of a novel recombinant virus assay to
      study entry inhibitor-resistant HIV variants using a biologically relevant cell
      type, primary CD4 T-cells. We have modified the replication-competent molecular
      clone HIV(NL4-3) to express a reporter protein (Renilla luciferase), Green
      Fluorescent Protein (EGFP), or Red Fluorescent Protein (DsRed2) upon infection,
      thus allowing quantification of replication. Luciferase-expressing virus was used
      to evaluate drug sensitivity, while co-infection with viruses carrying the green
      and red fluorescent proteins was employed in the competitive fitness assay. Using
      envelope proteins from three T20 insensitive variants, lower levels of resistance
      were observed in primary CD4 T-cells than had been previously reported for cell
      lines. Importantly, dual-color competition assays demonstrated comparable or
      higher fitness for these variants despite their reduced T20 sensitivity. We
      conclude that reduced sensitivity to T20 is compatible with high viral fitness in
      the absence of selection pressure. Thus, simultaneously measuring both resistance
      and viral fitness using this newly described dual-color competition assay will
      likely provide important information about resistant viral variants that emerge
      during therapy with entry inhibitors.

PMID- 15721361
TI  - The Bean pod mottle virus proteinase cofactor and putative helicase are symptom
      severity determinants.
AB  - Full-length infectious cDNA clones were constructed from the genomic RNAs of
      three distinct strains (K-G7, K-Ha1 and K-Ho1) of the comovirus Bean pod mottle
      virus (BPMV). Whereas K-G7, a subgroup I strain, and K-Ha1, a subgroup II strain
      produce mild mottling, the reassortant strain K-Ho1 (RNA1(I) + RNA2(II)) induces
      necrotic primary lesions on inoculated leaves of soybean and severe systemic leaf
      mottling and blistering. Pseudorecombinants of all possible combinations of
      transcripts were generated and tested for symptom production. Only soybean plants
      inoculated with combinations having RNA1 derived from the severe strain K-Ho1,
      regardless of the origin of RNA2, induced severe symptoms, indicating that
      symptom severity maps to RNA1. Experiments with chimeric RNA1 constructs
      indicated that the coding regions of the protease co-factor (Co-pro) and the C
      terminal half of the putative helicase (Hel) are determinants of symptom
      severity. Symptom severity correlated well with higher accumulation of viral RNA,
      but neither the Co-pro nor Hel protein could be demonstrated as a suppressor of
      RNA silencing.

PMID- 15721360
TI  - The N-terminal domain of the vaccinia virus E3L-protein is required for
      neurovirulence, but not induction of a protective immune response.
AB  - Encephalitis is a rare, but serious complication from vaccination against
      smallpox using replication competent strains of vaccinia virus. In this report we
      describe mutants of vaccinia virus, containing N-terminal deletions of the
      vaccinia virus interferon resistance gene, E3L, that are attenuated for
      neuropathogenesis in a mouse model system. These recombinant viruses replicated
      to high titers in the nasal mucosa after intra-nasal infection of C57BL/6 mice
      but failed to spread to the lungs or brain. These viruses demonstrated reduced
      pathogenicity after intra-cranial infection as well, indicating a decrease in
      neurovirulence. Intra-nasal inoculation or inoculation by scarification with a
      low dose of recombinant virus containing a deletion of the entire N-terminal
      domain of E3L protected against challenge with a high dose of wild-type vaccinia
      virus, suggesting that this replication competent, but attenuated strain of
      vaccinia virus may have promise as an improved vaccine for protecting against
      smallpox, and as a vector for inducing mucosal immunity to heterologous
      pathogenic organisms.

PMID- 15721362
TI  - Antiviral activity of human lactoferrin: inhibition of alphavirus interaction
      with heparan sulfate.
AB  - Human lactoferrin is a component of the non-specific immune system with distinct
      antiviral properties. We used alphaviruses, adapted to interaction with heparan
      sulfate (HS), as a tool to investigate the mechanism of lactoferrin's antiviral
      activity. Lactoferrin inhibited infection of BHK-21 cells by HS-adapted, but not
      by non-adapted, Sindbis virus (SIN) or Semliki Forest virus (SFV). Lactoferrin
      also inhibited binding of radiolabeled HS-adapted viruses to BHK-21 cells or
      liposomes containing lipid-conjugated heparin as a receptor analog. On the other
      hand, low-pH-induced fusion of the viruses with liposomes, which occurs
      independently of virus-receptor interaction, was unaffected. Studies involving
      preincubation of virus or cells with lactoferrin suggested that the protein does
      not bind to the virus, but rather blocks HS-moieties on the cell surface. Charge
      modified human serum albumin, with a net positive charge, had a similar antiviral
      effect against HS-adapted SIN and SFV, suggesting that the antiviral activity of
      lactoferrin is related to its positive charge. It is concluded that human
      lactoferrin inhibits viral infection by interfering with virus-receptor
      interaction rather than by affecting subsequent steps in the viral cell entry or
      replication processes.

PMID- 15721363
TI  - Differential dynamics of the peripheral and intrahepatic cytotoxic T lymphocyte
      response to hepatitis B surface antigen.
AB  - The distribution and dynamics of the cytotoxic T lymphocyte (CTL) response to
      hepatitis B surface antigen (HBsAg) were studied in mice after intramuscular DNA
      immunization and after hepatic infection by a recombinant adenovirus that
      expresses the hepatitis B virus genome (Ad-HBV). CTLs specific for HBsAg
      accumulate preferentially in the spleen after DNA immunization but are primarily
      intrahepatic after Ad-HBV infection. The secondary CTL response to Ad-HBV in DNA
      primed mice is characterized by rapid depletion of effector CTLs from the spleen,
      and their expansion in the liver where they cause hepatitis, secrete interferon
      gamma (IFNgamma), and inhibit HBV gene expression. Suppression of HBsAg synthesis
      is accompanied by disappearance of intrahepatic IFNgamma-producing CTLs and their
      reaccumulation in the spleen. The data suggest a possible explanation for the
      paucity and functional deficiency of HBV-specific CTLs in the periphery during
      chronic HBV infection, and that the severity of infection can be worsened by a
      preexisting CTL response if neutralizing antibody is not also present.

PMID- 15721364
TI  - Importance of sequence and structural elements within a viral replication
      repressor.
AB  - Efficient replication of plus-strand RNA viruses requires a 3' proximal core
      promoter and an increasingly diverse inventory of supporting elements such as
      enhancers, repressors, and 5' terminal sequences. While core promoters have been
      well characterized, much less is known about structure-functional relationships
      of these supporting elements. Members of the genus Carmovirus family
      Tombusviridae contain a hairpin (H5) proximal to the core promoter that functions
      as a repressor of minus-strand synthesis in vitro through an interaction between
      its large symmetrical internal loop (LSL) and 3' terminal bases. Turnip crinkle
      virus satellite RNA satC with the H5 of carmovirus Japanese iris necrosis virus
      or Cardamine chlorotic fleck virus (CCFV) did not accumulate to detectable levels
      even though 3' end base-pairing would be maintained. Replacement of portions of
      the satC H5 with analogous portions from CCFV revealed that the cognate LSL and
      lower stem were of greater importance for satC accumulation than the upper stem.
      In vivo selex of the H5 upper stem and terminal GNRA tetraloop revealed
      considerable plasticity in the upper stem, including the presence of three- to
      six-base terminal loops, allowed for H5 function. In vivo selex of the lower stem
      revealed that both a stable stem and specific base pairs contributed to satC
      fitness. Surprisingly, mutations in H5 had a disproportionate effect on plus
      strand accumulation that was unrelated to the stability of the mutant plus
      strands. In addition, fitness to accumulate in plants did not always correlate
      with enhanced ability to accumulate in protoplasts, suggesting that H5 may be
      multifunctional.

PMID- 15721365
TI  - Activation of c-Jun NH2-terminal kinase (JNK) signaling pathway is essential for
      the stimulation of hepatitis C virus (HCV) non-structural protein 3 (NS3)
      mediated cell growth.
AB  - Hepatitis C virus (HCV) non-structural protein 3 (NS3) has been shown to affect
      cellular functions and is thought to contribute to the development of HCV-related
      hepatocarcinogenesis. In this study, we delineated part of the mechanisms whereby
      NS3 protein stimulates cell growth in liver (HepG2) and non-liver (HeLa) cells.
      The expression of NS3 protein enhanced cell growth, c-jun NH(2)-terminal kinase
      (JNK) activation, DNA binding activities of the transcription factors AP-1 and
      ATF-2, and c-jun expression, but not the activation of extracellular signal
      regulated kinase (ERK) or p38(MAPK). Whereas co-expression of NS3 with its
      cofactor NS4A inhibited NS3-mediated cell growth without to influence NS3
      mediated JNK activation, or to affect the basal activities of ERK or p38(MAPK).
      Pre-treatment of NS3 protein-expressing cells with JNK inhibitor, SP600125,
      abolished activation of AP-1 and ATF-2 and inhibited c-jun expression and induced
      cell growth, suggesting that JNK activation is essential for the stimulation of
      NS3-mediated cell growth.

PMID- 15721366
TI  - Murine leukemia virus with a primer-binding site complementary to tRNALys,3
      adapts to select new tRNAs for replication following extended in vitro culture.
AB  - The preference of MuLV for the selection of tRNA(Pro) as a replication primer was
      investigated by altering the primer-binding site (PBS) to be complementary to
      tRNA(Lys,3). MuLV-based vectors with a PBS complementary to tRNA(Lys,3) were
      found to be approximately 2-fold less infectious than vectors with the wild-type
      PBS complementary to tRNA(Pro). MuLV with a PBS complementary to tRNA(Lys,3) was
      replication competent and maintained the PBS during early stages of in vitro
      culture. Upon extended culture, PBS were isolated which were complementary to
      tRNA(Arg). A second MuLV was generated in which the region upstream of the PBS
      which is predicted to form an RNA stem loop structure was altered so that the
      nucleotide sequence within the loop would be complementary to the anticodon of
      tRNA(Lys,3). The virus with both the U5 and PBS complementary to tRNA(Lys,3) was
      also replication competent. Upon extended in vitro culture though, this virus
      reverted to utilize tRNA(Lys1,2). Analysis of the infectivity and replication of
      the wild-type and mutant viruses revealed that tRNA(Pro) was the preferred tRNA
      for high-level replication. Viruses with a PBS complementary to tRNA(Arg) or
      tRNA(Ly1,2) replicated at levels approximately 30% and 10% as effective as the
      wild-type virus, while virus with a PBS complementary to tRNA(Lys,3) had the
      slowest replication kinetics and least infectivity. Comparison of the virion tRNA
      content of the wild-type and mutant viruses revealed similar ratios with respect
      to levels of tRNA(Pro), tRNA(Arg) and tRNA(Lys). Modeling of the U5-PBS region
      revealed that the predicted RNA structure for the virus that selected tRNA(Arg)
      was more similar to the wild type virus that uses tRNA(Pro) than the virus which
      use tRNA(Lys1,2) or tRNA(Lys,3); the virus that uses tRNA(Lys,3) had the most
      profound disruption in the predicted RNA structure. The results of these studies
      demonstrate that MuLV has evolved to preferentially select tRNA(Pro) for high
      level replication and are discussed with respect to common features of the primer
      selection process between MuLV and other retroviruses.

PMID- 15721367
TI  - Hepatitis C virus and the related bovine viral diarrhea virus considerably differ
      in the functional organization of the 5' non-translated region: implications for
      the viral life cycle.
AB  - The 5' non-translated regions (5'NTRs) of hepatitis C virus (HCV) and bovine
      viral diarrhea virus (BVDV) initiate translation of the viral RNA genome through
      an internal ribosomal entry site (IRES) and operate as major determinants of the
      RNA replication cycle. We report on comparative studies with both virus systems
      demonstrating that the functional organization of the 5'NTRs of HCV and BVDV
      shows evident differences despite a similar RNA structure. In the BVDV 5'NTR,
      replication signals are restricted to the 5' terminal domain I. With HCV, we
      defined specific replication signals in domain I but also in domains II and III
      that constitute the functional IRES. While the BVDV domain I supports IRES
      activity, the HCV domain I appears to down-regulate IRES function. These data
      suggest that HCV and BVDV apply different mechanisms to coordinate viral protein
      and RNA synthesis, which may explain differences in the replication efficiency of
      both related viruses.

PMID- 15721368
TI  - The Lettuce infectious yellows virus (LIYV)-encoded P26 is associated with
      plasmalemma deposits within LIYV-infected cells.
AB  - Cytological, immunological, and mutagenesis approaches were used to identify the
      viral factors associated with the formation of plasmalemma deposits (PLDs) in
      whole plants and protoplasts infected by Lettuce infectious yellows virus (LIYV).
      Transmission electron microscopy and immunogold labeling using polyclonal
      antibodies to four of the five LIYV RNA 2-encoded large proteins, capsid protein
      (CP), minor capsid protein (CPm), HSP70 homolog (HSP70h), and P59, showed
      specific labeling of LIYV virions or virion aggregates around the vesiculated
      membranous inclusions, but not PLDs in LIYV-infected Nicotiana benthamiana,
      Nicotiana clevelandii, Lactuca sativa, and Chenopodium murale plants, and
      Nicotiana tabacum protoplasts. In contrast, antibodies to the RNA 2-encoded P26
      showed specific labeling of PLDs but not virions in both LIYV-infected plants and
      protoplasts. Virion-like particles (VLPs) were seen in protoplasts infected by
      all LIYV RNA 2 mutants except for the CP (major capsid protein) mutant. PLDs were
      more difficult to find in protoplasts, but were seen in protoplasts infected by
      the CP and CPm mutants, but not in protoplasts infected by the P26, HSP70h, or
      P59 mutants. Interestingly, although the CPm mutant showed VLPs and PLDs, the
      PLDs did not show associated virions/virion-like particles as was always observed
      for PLDs seen in protoplasts infected by wild-type LIYV. Immunoblot analyses
      performed on purified LIYV virions showed that P26 was not detected with purified
      virions, but was detected in the cell wall, 1000 g and 30,000 g pellet fractions
      of LIYV-infected plants. These data suggest that P26 is associated with the LIYV
      induced PLDs, and in contrast to the other RNA 2-encoded large proteins, P26 is
      not a virion protein.

PMID- 15721369
TI  - Complementary function of the two catalytic domains of APOBEC3G.
AB  - The HIV-1 viral accessory protein Vif prevents the encapsidation of the antiviral
      cellular cytidine deaminases APOBEC3F and APOBEC3G by inducing their proteasomal
      degradation. In the absence of Vif, APOBEC3G is encapsidated and blocks virus
      replication by deaminating cytosines of the viral cDNA. APOBEC3G encapsidation
      has been recently shown to depend on the viral nucleocapsid protein; however, the
      role of RNA remains unclear. Using APOBEC3G deletion and point mutants, we mapped
      the encapsidation determinant to the Zn(2+) coordination residues of the N
      terminal catalytic domain (CD1). Notably, these residues were also required for
      RNA binding. Mutations in the two aromatic residues of CD1 but not CD2, which are
      conserved in cytidine deaminase core domains and are required for RNA binding,
      prevented encapsidation into HIV-1, HTLV-I and MLV. The Zn(2+) coordination
      residues of the C-terminal catalytic domain (CD2) were not required for
      encapsidation but were essential for cytidine deaminase activity and the
      antiviral effect. These findings suggest a model in which CD1 mediates
      encapsidation and RNA binding while CD2 mediates cytidine deaminase activity.
      Interestingly, HTLV-I was relatively resistant to the antiviral effects of
      encapsidated APOBEC3G.

PMID- 15721373
TI  - Preparation, characterization, and biological analysis of liposomal formulations
      of vincristine.
AB  - Vincristine is a dimeric Catharanthus alkaloid derived from the Madagascan
      periwinkle that acts by binding to tubulin and blocking metaphase in actively
      dividing cells. While vincristine is widely used in the treatment of a number of
      human carcinomas, its use is associated with dose-limiting neurotoxicity,
      manifested mainly as peripheral neuropathy. It is known that the therapeutic
      activity of vincristine can be significantly enhanced after its encapsulation in
      appropriately designed liposomal systems. Enhanced efficacy is also associated
      with a slight decrease in drug toxicity. Thus, the therapeutic index of
      vincristine can be enhanced significantly through the use of a liposomal delivery
      system. Vincristine may be encapsulated into liposomes of varying lipid
      composition by several techniques, including passive loading, pH gradient
      loading, and ionophore-assisted loading. However, most research has focused on
      the encapsulation of vincristine in response to a transbilayer pH gradient, which
      actively concentrates the drug within the aqueous interior of the liposome. This
      chapter details the preparation and evaluation of liposomal vincristine.
      Specifically, we elaborate on the components (choice of lipids, molar
      proportions, etc.), methods (preparation of liposomes, drug loading methods,
      etc.), critical design features (size, surface charge, etc.), and key biological
      endpoints (circulation lifetime, bioavailability, efficacy measurements)
      important to the development of a formulation of vincristine with enhanced
      therapeutic properties.

PMID- 15721372
TI  - Entrapment of small molecules and nucleic acid-based drugs in liposomes.
AB  - In the past two decades there have been major advances in the development of
      liposomal drug delivery systems suitable for applications ranging from cancer
      chemotherapy to gene therapy. In general, an optimized system consists of
      liposomes with a diameter of approximately 100 nm that possess a long circulation
      lifetime (half-life >5 h). Such liposomes will circulate sufficiently long to
      take advantage of a phenomenon known as disease site targeting, wherein liposomes
      accumulate at sites of disease, such as tumors, as a result of the leaky
      vasculature and reduced blood flow exhibited by the diseased tissue. The extended
      circulation lifetime is achieved by the use of saturated lipids and cholesterol
      or by the presence of PEG-containing lipids. This chapter will focus on the
      methodology required for the generation of two very different classes of
      liposomal carrier systems: those containing conventional small molecular weight
      (usually anticancer) drugs and those containing larger genetic (oligonucleotide
      and plasmid DNA) drugs. Initially, we will examine the encapsulation of small,
      weakly basic drugs within liposomes in response to transmembrane pH and ion
      gradients. Procedures will be described for the formation of large unilamellar
      vesicles (LUVs) by extrusion methods and for loading anticancer drugs into LUVs
      in response to transmembrane pH gradients. Three methods for generating
      transmembrane pH gradients will be discussed: (1) the use of intravesicular
      citrate buffer, (2) the use of transmembrane ammonia gradients, and (3) ionophore
      mediated generation of pH gradients via transmembrane ion gradients. We will also
      discuss the loading of doxorubicin into LUVs by formation of drug-metal ion
      complexes. Different approaches are required for encapsulating macromolecules
      within LUVs. Plasmid DNA can be encapsulated by a detergent-dialysis approach,
      giving rise to stabilized plasmid-lipid particles, vectors with potential for
      systemic gene delivery. Antisense oligonucleotides can be spontaneously entrapped
      upon electrostatic interaction with ethanol-destabilized cationic liposomes,
      giving rise to small multilamellar systems known as stabilized antisense-lipid
      particles (SALP). These vectors have the potential to regulate gene expression.

PMID- 15721374
TI  - Lipophilic arabinofuranosyl cytosine derivatives in liposomes.
AB  - Highly lipophilic drugs can be used therapeutically only by the addition of
      possibly toxic solubilizing agents or by development of complex pharmaceutical
      formulations. One way of overcoming these disadvantages is the incorporation of
      such drugs into the bilayer matrix of phospholipid liposomes. To this end, we
      chose the approach of chemical transformation of water-soluble nucleosides of
      known cytotoxic properties into lipophilic drugs or prodrugs. Due to their
      insolubility, we developed formulations that can be used for intravenous
      applications in which the lipophilic molecules are incorporated into lipid
      bilayer membranes of small liposomes. We chose 1-beta-d-arabinofuranosylcytosine
      (ara-C) as a cytotoxic nucleoside, and we demonstrated that N(4)-acyl derivatives
      of ara-C were active in vivo in various murine tumor models as liposomal
      formulations. However, the protection against enzymatic deamination was only
      partially achieved and was insufficient for significant improvement of cytotoxic
      properties. Thus, we synthesized a new class of N(4)-alkyl-ara-C derivatives. The
      most effective derivative, N(4)-octadecyl-ara-C (NOAC), is highly lipophilic and
      extremely resistant toward deamination. NOAC exerts excellent antitumor activity
      after oral and parenteral therapy. The activity of NOAC against freshly explanted
      clonogenic cells from human tumors was determined and compared with conventional
      antitumor agents. NOAC was used in two liposomal preparations, a stable
      lyophilized and a freshly prepared liquid formulation. Both formulations
      inhibited tumor colony formation equally in a concentration-dependent fashion. At
      optimal conditions, liposomal NOAC had significantly better activity compared
      with the clinically used drugs cisplatin, doxorubicin, 5-fluorouracil,
      gemcitabine, mitomycin C, and etoposide. Furthermore, in a hematopoietic stem
      cell assay, NOAC was less toxic than ara-C and doxorubicin by factors ranging
      from 2.5 to 200, indicating that this drug is well tolerated at high doses.

PMID- 15721375
TI  - The liposomal formulation of doxorubicin.
AB  - Doxorubicin is the best known and most widely used member of the anthracycline
      antibiotic group of anticancer agents. It was first introduced in the 1970s, and
      since that time has become one of the most commonly used drugs for the treatment
      of both hematological and solid tumors. The therapy-limiting toxicity for this
      drug is cardiomyopathy, which may lead to congestive heart failure and death.
      Approximately 2% of patients who have received a cumulative (lifetime)
      doxorubicin dose of 450-500 mg?m(2) will experience this condition. An approach
      to ameliorating doxorubicin-related toxicity is to use drug carriers, which
      engender a change in the pharmacological distribution of the drug, resulting in
      reduced drug levels in the heart. Examples of these carrier systems include lipid
      based (liposome) formulations that effect a beneficial change in doxorubicin
      biodistribution, with two formulations approved for clinical use. Drug approval
      was based, in part, on data suggesting that beneficial changes in doxorubicin
      occurred in the absence of decreased therapeutic activity. Preclinical (animal)
      and clinical (human) studies showing that liposomes can preferentially accumulate
      in tumors have provided a rationale for improved activity. Liposomes represent
      ideal drug delivery systems, as the microvasculature in tumors is typically
      discontinuous, having pore sizes (100-780 nm) large enough for liposomes to move
      from the blood compartment into the extravascular space surrounding the tumor
      cells. Liposomes, in the size range of 100-200 nm readily extravasate within the
      site of tumor growth to provide locally concentrated drug delivery, a primary
      role of liposomal formulation. Although other liposomal drugs have been prepared
      and characterized due to the potential for liposomes to improve antitumor potency
      of the encapsulated drug, the studies on liposomal doxorubicin have been
      developed primarily to address issues of acute and chronic toxicity that occur as
      a consequence of using this drug. It is important to recognize that research
      programs directed toward the development of liposomal doxorubicin occurred
      concurrently with synthetic chemistry programs attempting to introduce safer and
      more effective anthracycline analogues. Although many of these drugs are approved
      for use, and preliminary liposomal formulations of these analogues have been
      prepared, doxorubicin continues to be a mainstay of drug cocktails used in the
      management of most solid tumors. It will be of great interest to observe how the
      approved formulations of liposomal doxorubicin are integrated into combination
      regimes for treatment of cancer. In the meantime, we have learned a great deal
      about liposomes as drug carriers from over 20 years of research on different
      liposomal doxorubicin formulations, the very first of which were identified in
      the late 1970s. This chapter will discuss the various methods for encapsulation
      of doxorubicin into liposomes, as well as some of the important interactions
      between the formulation components of the drug and how this may impact the
      biological activity of the associated drug. This review of methodology, in turn,
      will highlight research activities that are being pursued to achieve better
      performance parameters for liposomal formulations of doxorubicin, as well as
      other anticancer agents being considered for use with lipid-based carriers.

PMID- 15721376
TI  - Preparation and characterization of taxane-containing liposomes.
AB  - Drug carriers such as liposomes provide a means to alter the biodisposition of
      drugs and to achieve concentration-time exposure profiles in tissue or tumor that
      are not readily accomplished with free drug. These changes in biodisposition can
      improve treatment efficacy. For hydrophobic drugs, incorporation in liposome
      carriers can increase drug solubility markedly. The taxanes paclitaxel (taxol)
      and docetaxel (Taxotere) are members of one of the most important new classes of
      oncology drugs. However, their poor solubility presents pharmaceutical
      challenges, and emerging data suggest that specific tissue exposure profiles,
      such as low drug concentrations for extended times, can enhance beneficial
      antitumor mechanisms. Incorporation of the taxanes into liposomes eliminates not
      only the toxic effects of cosolvents required to administer these drugs
      clinically but also increases drug efficacy in animal tumor models, usually
      through a reduction in dose-limiting tissue toxicities. Although the taxanes are
      poorly water soluble, the preparation of physically stabile taxane-liposome
      formulations requires the balancing of three factors: (1) the drug:lipid ratio,
      (2) the liposome composition, and (3) the duration of storage in aqueous media.
      Biophysical evaluation of formulation characteristics, principally using circular
      dichroism (CD) and differential scanning calorimetry (DSC), can provide the
      information necessary to develop stable taxane-liposome formulations. These
      techniques provide information on drug-drug and drug-lipid interactions that
      underlie the events that lead to taxane formulation instability. Owing to the
      unusually low solubility of the taxanes, special consideration is necessary to
      devise methods for resolving drug-containing liposomes from released or
      precipitated drug to obtain reliable estimates of drug incorporation and
      retention in liposomes.

PMID- 15721377
TI  - Cisplatin nanocapsules.
AB  - Cisplatin nanocapsules represent a novel lipid formulation of the anticancer drug
      cis-diamminedichloroplatinum(II), in which nanoprecipitates of cisplatin are
      covered by a phospholipid bilayer coat consisting of an equimolar mixture of
      phosphatidylcholine and phosphatidylserine. Cisplatin nanocapsules are
      characterized by an unprecedented cisplatin-to-lipid molar ratio and exhibit
      strongly improved cytotoxicity against tumor cells in vitro compared with the
      free drug. Here, methods for preparing and characterizing cisplatin nanocapsules
      are reported.

PMID- 15721378
TI  - Liposomal cytokines in the treatment of infectious diseases and cancer.
AB  - Despite of the demonstrated activity of cytokines in vitro, their use in the
      clinical setting is often disappointing. Cytokine-related toxicity seriously
      limits optimal use in vivo. In addition, rapid degradation and excretion,
      neutralization and binding to receptors, or metabolization of the molecule
      results in a short half-life in serum when injected intravenously. As the dose
      response curve of cytokines is relatively steep, outcome greatly benefits from
      improved delivery and bioavailability. One way to improve the pharmacokinetics of
      cytokines after systemic application is encapsulation in liposomes. An advantage
      of liposomes is that the encapsulated drug is protected from (rapid) degradation
      and excretion, and it eliminates the binding to neutralizing antibodies or
      (soluble) receptors. Moreover, liposomes can be tailored in such a way that they
      exhibit favorable pharmacokinetics, i.e., increased serum half-life and improved
      targeting to tissues or cells of interest. In this chapter, the use of liposomal
      cytokines in the treatment of cancer and infectious disease is discussed.

PMID- 15721379
TI  - Glucuronate-modified, long-circulating liposomes for the delivery of anticancer
      agents.
AB  - Liposomes are useful as drug carriers in drug delivery systems, especially for
      drugs with severe side effects such as antitumor agents. The conventional
      formulations of liposomes are opsonized by plasma proteins in the bloodstream and
      trapped in the reticuloendothelial system (RES). Therefore, liposomes with
      reduced opsonization are expected to have prolonged circulation and to accumulate
      in tumor tissue due to the leaky endothelium of the tissue. To avoid RES trapping
      of liposomes, two approaches have been considered. Liposomes may mimic cells
      circulating in the blood to escape host recognition as foreign substances, or
      liposomes may be covered with a hydrophilic barrier to escape recognition. For
      the latter purpose, poly(ethylene glycol) is widely used. For the former purpose,
      here we focus on the characteristics, in vivo trafficking, and usage in cancer
      therapy of glucuronate-modified liposomes. Glucuronate-modified liposomes bind to
      a lower extent to macrophage-like cells in vitro and passively accumulate in
      tumor tissue evaluated by a technique using positron emission tomography.
      Glucuronate-modified liposomes with extended circulation are useful for
      delivering anticancer agents to tumors and reducing the toxic side effects of the
      agents.

PMID- 15721380
TI  - Liposomalized oligopeptides in cancer therapy.
AB  - Organ-specific delivery of biofunctional agents is thought to enhance their
      activity and to reduce their side effects. Liposomes have been used as drug
      carriers in cancer chemotherapy, since they accumulate passively in tumor tissues
      due to an enhanced permeability and retention (EPR) effect. In addition,
      modification of liposomes with specific ligands enables active targeting. A small
      peptide having a high affinity for a certain antigen is suitable for modification
      of liposomes, since it is biocompatible, biodegradable, and less antigenic
      compared with antibody and other modifiers. Oligopeptide-modified liposomes are
      prepared by using lipophilic derivatives of the peptide, which are synthesized
      easily and incorporated readily into the liposomal bilayer. We describe two
      examples of the use of liposomal oligopeptides: one for antimetastatic therapy
      and the other for antineovascular therapy. Arg-Gly-Asp (RGD)-related peptides are
      known to contribute various cellular functions such as adhesion and invasion and
      to inhibit tumor metastasis. However, peptide drugs are generally rapidly
      hydrolyzed and eliminated from the bloodstream. Liposomal RGD enables the half
      lives and affinity to be improved, resulting in enhancement of antimetastatic
      activity. We then describe the usefulness of liposomal Ala-Pro-Arg-Pro-Gly
      (APRPG) for tumor treatment, which is specific for tumor angiogenic vessels.
      APRPG is originally isolated by use of a phage-displayed peptide library.
      Adriamycin encapsulated in APRPG-modified liposomes accumulated specifically in
      and damage tumor neovessels, resulting in notable antitumor efficacy.

PMID- 15721381
TI  - Separation of liposome-entrapped mitoxantrone from nonliposomal mitoxantrone in
      plasma: pharmacokinetics in mice.
AB  - A method is described for quantification of the liposomal and nonliposomal forms
      of mitoxantrone (MTO) in mouse plasma after intravenous administration of
      liposome-entrapped MTO Easy-to-Use (LEM-ETU) formulation. This is based on the
      property of liposome-entrapped MTO (LEM) to pass through reversed-phase C(18)
      silica gel cartridges, while nonliposomal MTO or free MTO is retained with strong
      hydrophobicity and later is eluted with acidic methanol. Extraction of LEM and
      free MTO from plasma is performed in two steps. This technique is rapid and
      sensitive and can be used for a large series of sample preparation. The plasma
      samples are found stable after one freeze-thaw cycle. The recovery of MTO, as
      well as the precision, linearity, and accuracy of the method for both free and
      liposomal MTO, appears satisfactory for pharmacokinetic studies. The
      pharmacokinetic results in mice show a sustained release of MTO from LEM-ETU.

PMID- 15721382
TI  - Methodology and experimental design for the study of liposome-dependent drugs.
AB  - This chapter describes the concept of liposome-dependent drugs and the rationale
      for using them. Subsequently, procedures for studying and identifying liposome
      dependent drugs are given. The first procedure described is a simple endpoint
      assay, and methods are given for both adherent and nonadherent cells. To
      establish in such a system that a drug is liposome dependent, it is necessary to
      demonstrate an IC(50) for the encapsulated drug that is less than that of the
      free drug, preferably with continuous exposure of the cells to drug.
      Subsequently, a second procedure is described, which is a more rigorous approach
      able to identify liposome dependency for a drug that is less effective in a
      carrier system than it is in the free form. This procedure is a multicompartment
      growth inhibition assay, wherein two cell populations are separated by a
      semipermeable membrane, through which free drug but not the liposomal carrier
      system may diffuse. The first population is adherent and is directly exposed to
      the liposomal or free drug. The second cell population is nonadherent and is
      exposed only to the drug that diffuses through the membrane. In addition to the
      methodology, experimental design is discussed and also the calculations needed to
      determine percent leakage, percent processing, percent metabolism, and the
      delivery factor, a parameter equivalent to a therapeutic index in an in vivo
      study.

PMID- 15721383
TI  - Liposome-mediated suicide gene therapy in humans.
AB  - The LIPO-HSV-1-tk gene transfer system was developed for a 3-day pump application
      in a first prospective Phase I?II clinical study. Eight patients suffering from
      recurrent glioblastoma multiforme were treated intratumorally on the basis of
      convection-enhanced delivery using the nonviral vector system. It was possible to
      identify the target tissue together with assessment of vector distribution and
      gene product expression, as well as the metabolic effect of ganciclovir
      treatment, noninvasively, by the combination of magnetic resonance imaging and
      positron emission tomography as a multimodal molecular imaging system. The
      therapy was well tolerated without major side effects. In two of eight patients,
      we observed a greater than 50% reduction of tumor volume and in six of eight
      patients focal treatment effects. The noninvasive visualization of therapeutic
      effects on tumor metabolism and documentation of gene expression will be
      important for the further successful development and implementation of patient
      individual gene therapy.

PMID- 15721384
TI  - Use of liposomes to deliver bactericides to bacterial biofilms.
AB  - Methods are described for the preparation of anionic and cationic liposomes and
      proteoliposomes with covalently linked lectins or antibodies by the extrusion
      technique (vesicles by extrusion, VETs). The liposomes are prepared from the
      phospholipid dipalmitoylphosphatidylcholine (DPPC), together with the anionic
      lipid phosphatidylinositol (PI) or the cationic amphiphile
      dioctadecyldimethylammonium bromide (DDAB) together with the reactive lipid DPPE
      MBS, the m-maleimidobenzoyl-N-hydroxysuccinimide (MBS) derivative of
      dipalmitoylphosphatidylethanolamine (DPPE). Proteins (lectin or antibody), after
      derivatization with N-succinimidyl-S-acetylthioacetate (SATA), can be covalently
      linked to the surface of the liposomes by reaction with the reactive lipid, DPPE
      MBS. The physical and chemical characterization of the liposomes and
      proteoliposomes by photon correlation spectroscopy (PCS) and protein analysis, to
      determine the number of chemically linked protein molecules (lectin or antibody)
      per liposome, are described. The liposomes can be used for carrying oil-soluble
      bactericides (e.g., Triclosan) or water-soluble antibiotics (e.g., vancomycin or
      benzylpenicillin) and targeted to immobilized bacterial biofilms of oral or skin
      associated bacteria adsorbed on microtiter plates. Techniques for the preparation
      of immobilized bacterial biofilms, applicable to a wide range of bacterial
      suspensions, and for the analysis of the adsorption (targeting) of the liposomes
      to the bacterial biofilms are given. The mode of delivery and assessment of
      antibacterial activity of liposomes encapsulating bactericides and antibiotics,
      when targeted to the bacterial biofilms, by use of an automated microtiter plate
      reader, are illustrated, with specific reference to the delivery of the
      antibiotic benzylpenicillin encapsulated in anionic liposomes to biofilms of
      Staphylococcus aureus. The methods have potential application for the delivery of
      oil-soluble or water-soluble bactericidal compounds to a wide range of adsorbed
      bacteria responsible for infections in implanted devices such as catheters, heart
      valves, and artificial joints.

PMID- 15721385
TI  - Long-circulating sterically stabilized liposomes in the treatment of infections.
AB  - The administration of antimicrobial agents encapsulated in long-circulating
      sterically stabilized liposomes results in a considerable enhancement of
      therapeutic efficacy compared with the agents in the free form. After liposomal
      encapsulation, the pharmacokinetics of the antimicrobial agents is significantly
      changed. An increase in circulation time and reduction in toxic side effects of
      the agents are observed. In contrast to other types of long-circulating
      liposomes, an important characteristic of these sterically stabilized liposomes
      is that their prolonged blood circulation time is, to a high degree, independent
      of liposome characteristics such as liposome particle size, charge and lipid
      composition (rigidity) of the bilayer, and lipid dose. This provides the
      opportunity to manipulate antibiotic release from these liposomes at the site of
      infection, which is important in view of the differences in pharmacodynamics of
      different antibiotics and can be done without compromising blood circulation time
      and degree of target localization of these liposomes. Depending on the liposome
      characteristics and the agent encapsulated, antibiotic delivery to the infected
      site is achieved, or the liposomes act as a micro-reservoir function for the
      antibiotic. In experimental models of localized or disseminated bacterial and
      fungal infections, the sterically stabilized liposomes have successfully been
      used to improve antibiotic treatment using representative agents of various
      classes of antibacterial agents such as the beta-lactams, the aminoglycosides,
      and the quinolones or the antifungal agent amphotericin B. Extensive
      biodistribution studies have been performed. Critical factors that contribute to
      liposome target localization in infected tissue have been elucidated. Liposome
      related factors that were investigated were poly(ethylene glycol) density,
      particle size, bilayer fluidity, negative surface charge, and circulation
      kinetics. Host-related factors focused on the components of the inflammatory
      response.

PMID- 15721386
TI  - Liposome-encapsulated antibiotics.
AB  - Encapsulation of certain antibiotics in liposomes can enhance their effect
      against microorganisms invading cultured cells and in animal models. We describe
      the incorporation of amikacin, streptomycin, ciprofloxacin, sparfloxacin, and
      clarithromycin in a variety of liposomes. We delineate the methods used for the
      evaluation of their efficacy against Mycobacterium avium-intracellulare complex
      (MAC) infections in macrophages and in the beige mouse model of MAC disease. We
      also describe the efficacy of pH-sensitive liposomes incorporating sparfloxacin
      or azithromycin. We summarize studies with other antibiotics, including
      rifampicin, rifabutin, ethambutol, isoniazid, clofazimine, and enrofloxacin, and
      their use against MAC, as well as other infection models, including Mycobacterium
      tuberculosis.

PMID- 15721387
TI  - Tuftsin-bearing liposomes as antibiotic carriers in treatment of macrophage
      infections.
AB  - Tuftsin is a tetrapeptide (Thr-Lys-Pro-Arg) that specifically binds monocytes,
      macrophages, and polymorphonuclear leukocytes and potentiates their natural
      killer activity against tumors and pathogens. The antimicrobial activity of this
      peptide is significantly increased by attaching at the C-terminus a fatty acyl
      residue through the ethylenediamine spacer arm. This activity is further
      augmented by incorporating the modified tuftsin in the liposomes. The tuftsin
      bearing liposomes not only enhance the host's resistance against a variety of
      infections but also serve as useful vehicles for the site-specific delivery of
      drugs in a variety of macrophage-based infections, such as tuberculosis and
      leishmaniasis.

PMID- 15721388
TI  - Liposomal polyene antibiotics.
AB  - Polyene antibiotics (i.e., amphotericin B and nystatin) have been incorporated
      into lipid-based delivery systems to decrease their toxicity and enhance their
      therapeutic index, the most common being liposomes. This chapter describes the
      protocols for preparing liposomal amphotericin B and determining the efficacy and
      toxicity of the formulations in animals. Furthermore, methods for determining the
      pharmacokinetics and drug distribution after administration of amphotericin B in
      lipid-based delivery systems are discussed. Procedures for comparing the toxicity
      of different amphotericin B formulations in cell culture studies are also
      elucidated.

PMID- 15721389
TI  - Drug delivery by lipid cochleates.
AB  - Drug delivery technology has brought additional benefits to pharmaceuticals such
      as reduction in dosing frequency and side effects, as well as the extension of
      patient life. To address this need, cochleates, a precipitate obtained as a
      result of the interaction between phosphatidylserine and calcium, have been
      developed and proved to have potential in encapsulating and delivering small
      molecule drugs. This chapter discusses the molecules that can be encapsulated in
      a cochleate system and describes in detail the methodology that can be used to
      encapsulate and characterize hydrophobic drugs such as amphotericin B, a potent
      antifungal agent. Some efficacy data in animal models infected with candidiasis
      or aspergillosis are described as well.

PMID- 15721390
TI  - Lymphoid tissue targeting of anti-HIV drugs using liposomes.
AB  - Considering that HIV-1 accumulates and replicates actively within lymphoid
      tissues, any strategy that will decrease viral stores in these tissues might be
      beneficial to the infected host. Follicular dendritic cells (FDC), B lymphocytes,
      antigen-presenting cells like macrophages, and activated CD4(+) T cells are
      abundant in lymphoid tissues, and all express substantial levels of the HLA-DR
      determinant of the major histocompatibility complex class II (MHC-II). Monocyte
      derived macrophages, which are also CD4(+) and express HLA-DR, are considered to
      be the most frequent hosts of HIV-1 in tissues of infected individuals. This
      chapter describes a method for the generation of sterically stabilized
      immunoliposomes grafted with anti-HLA-DR antibodies that allows efficient
      delivery of drugs to lymphoid tissues. The method first involves the production
      of murine HLA-DR (clone Y-17, IgG(2b)) and human HLA-DR (clone 2.06, IgG(1))
      antibodies from hybridomas in mice and their purification from ascites fluids.
      This step is followed by the production of Fab' fragments of antibodies 2.06 and
      Y-17 that are grafted at the surface of sterically stabilized immunoliposomes
      instead of the complete IgG to reduce their immunogenicity. The preparation of
      sterically stabilized liposomes, the composition of which allows an efficient
      entrapment and retention of several drugs, by the method of thin lipid film
      hydratation followed by extrusion through polycarbonate membranes is then
      described. This step is followed by the removal of unencapsulated drug, when
      present, by low-speed centrifugation of the liposomal preparation through a
      Sephadex G-50 column. These liposomes contain a fixed amount of poly(ethylene
      glycol) chain terminated by a maleimide reactive group for the coupling of Fab'
      fragments. The procedure for the coupling of Fab' fragments at the surface of
      sterically stabilized liposomes and the removal of uncoupled fragments of
      antibodies is described. In vitro binding studies of sterically stabilized
      immunoliposomes to cell lines expressing different surface levels of the mouse or
      human HLA-DR determinant of MHC-II demonstrate that these liposomes are very
      specific. When compared with conventional liposomes, the subcutaneous
      administration in the upper back, below the neck, of mice of anti-HLA-DR
      immunoliposomes resulted in a 2.9 and 1.6 times greater accumulation in the
      cervical and brachial lymph nodes, respectively. The use of sterically stabilized
      immunoliposomes increases 2 to 4.6 times the concentration of liposomes in all
      tissues, with a peak accumulation at 240 h in brachial, inguinal, and popliteal
      lymph nodes and at 360 h or greater in cervical lymph nodes. A single bolus
      injection of indinavir given subcutaneously to mice results in no significant
      drug levels in lymphoid organs. Most of the injected drug accumulates in the
      liver and is totally cleared within 24 h postadministration. In contrast,
      sterically stabilized immunoliposomes are very efficient in delivering high
      concentrations of indinavir to lymphoid tissues for at least 15 days
      postinjection. The drug accumulation in all tissues leads to a 21- to 126-fold
      increased accumulation when compared with the free agent. Anti-HLA-DR
      immunoliposomes containing indinavir are as efficient as the free agent in
      inhibiting HIV-1 replication in PM1 cells that express high levels of cell
      surface HLA-DR. Sterically stabilized anti-HLA-DR immunoliposomes mostly
      accumulate in the cortex in which follicles (B cells and FDCs) are located, and
      in parafollicular areas in which T cells, interdigitating dendritic cells, and
      other accessory cells are abundant. The delivery of drugs in this area of the
      lymph nodes could represent a convenient strategy to inhibit more efficiently HIV
      1 replication. Although the method described in this chapter is specific to the
      coupling of anti-HLA-DR antibodies, any antibody fragment or peptide specific for
      an antigen present in relatively large quantities at the surface of lymphoid
      cells, that is anchored to the surface of sterically stabilized liposomes with an
      appropriate coupling method, can be used to concentrate drugs within target
      tissues and improve the therapeutic effect of drugs.

PMID- 15721392
TI  - Liposomal vasoactive intestinal peptide.
AB  - Liposomes have been investigated as drug carriers since first discovered in the
      1960s. However, the first-generation, so-called classic liposomes found
      relatively limited therapeutic utility. Nonetheless, the advent in the 1980s of
      the second-generation sterically stabilized liposomes (SSL) that evade uptake by
      the host's reticuloendothelial system greatly enhanced their utility as drug
      carriers because of their prolonged circulation half-life and passive targeting
      to injured and cancerous tissues. Over the past decade, our work focused on
      exploiting the bioactivity of vasoactive intestinal peptide (VIP), a ubiquitous
      28-amino acid, amphipathic and pleiotropic mammalian neuropeptide, as a drug. To
      this end, the peptide expresses distinct and unique innate bioactivity that could
      be harnessed to treat several human diseases that represent unmet medical needs,
      such as pulmonary hypertension, stroke, Alzheimer's disease, sepsis, female
      sexual arousal dysfunction, acute lung injury, and arthritis. Unfortunately, the
      bioactive effects of VIP last only a few minutes due to its rapid degradation and
      inactivation by enzymes, catalytic antibodies, and spontaneous hydrolysis in
      biological fluids. Hence, our goal was to develop and test stable, long-acting
      formulations of VIP using both classic and SSL as platform technologies. We found
      that spontaneous association of VIP with phospholipid bilayers leads to a
      transition in the conformation of the peptide from random coil in an aqueous
      environment to alpha-helix, the preferred conformation for ligand-receptor
      interactions, in the presence of lipids. This process, in turn, protects VIP from
      degradation and inactivation and amplifies its bioactivity in vivo. Importantly,
      we discovered that the film rehydration and extrusion technique is the most
      suitable to passively load VIP onto SSL at room temperature and yields the most
      consistent results. Collectively, these attributes indicate that VIP on SSL
      represents a suitable formulation that could be tested in human disease.

PMID- 15721391
TI  - Delivery of antiviral agents in liposomes.
AB  - The intracellular activity of certain antiviral agents, including antisense
      oligonucleotides, acyclic nucleoside phosphonates, and protease inhibitors, is
      enhanced when they are delivered in liposome-encapsulated form. In this chapter
      we describe the preparation of pH-sensitive liposomes encapsulating antisense
      oligonucleotides, ribozymes, and acyclic nucleoside phosphonate analogues and
      their effects on HIV replication in macrophages. We outline the use of liposomal
      HIV protease inhibitors in infected macrophages. We present two methods for the
      covalent coupling of soluble CD4 to liposomes and show the association of these
      liposomes with HIV-infected cells. We also describe the synthesis of a novel
      antiviral agent based on cyclodextrin and its incorporation into liposomes.

PMID- 15721394
TI  - The use of sterically stabilized liposomes to treat asthma.
AB  - Asthma is characterized by airway hyperresponsiveness, chronic inflammation, and
      airway remodeling, which may lead to progressive, irreversible lung damage.
      Liposomes have been used for the delivery of aerosolized asthma medications into
      the lungs. This method could facilitate sustained action of steroids while using
      only a fraction of the dosage and a less frequent dosing interval than
      conventional therapy. We describe the evaluation of the effect of budesonide
      encapsulated in sterically stabilized liposomes on lung inflammation and airway
      hyperreactivity in a mouse model of asthma. We outline the determination of
      markers implicated in the progression of asthma, including histopathology,
      eosinophil peroxidase activity in bronchoalveolar lavage, and airway
      hyperresponsiveness to methacholine. Weekly administration of budesonide in
      sterically stabilized liposomes results in a significant reduction in the total
      lung inflammation score, peripheral blood eosinophil counts, and the total serum
      IgE level, similar to that obtained with daily budesonide. Airway
      hyperresponsiveness to methacholine challenge decreases significantly in the
      group treated with weekly budesonide in sterically stabilized liposomes, while it
      does not decrease in the daily budesonide group.

PMID- 15721393
TI  - Liposomal superoxide dismutases and their use in the treatment of experimental
      arthritis.
AB  - It has long been suggested that superoxide dismutase (SOD) be used for
      antioxidant therapy on the basis of its ability to catalyze the dismutation of
      superoxide radicals involved in the pathogenesis of several inflammatory
      disorders such as rheumatoid arthritis. However, the administration of SOD in
      free form has some disadvantages, most importantly, the low accumulation of SOD
      in inflamed areas due to its reduced half-life in the bloodstream and its rapid
      renal excretion. To overcome this, SOD can be incorporated either in highly
      loaded conventional liposomes (SA-liposomes) or long circulating liposomes (PEG
      liposomes). After an appropriate formulation of SOD in SA-liposomes, the
      therapeutic effect is strongly increased, as indicated by a reduction of about
      40% of inflammation edema compared with treatment with nonencapsulated enzyme.
      Compared with SA-liposomes, PEG-liposomes show superior therapeutic activity. A
      second approach consists of the construction of a hydrophobic SOD derivative (Ac
      SOD) that can be partially inserted within the lipid matrix of liposomes and that
      expresses enzymatic activity to the external medium. This hydrophobic enzyme, Ac
      SOD, associated with liposomes (so called Ac-SOD-enzymosomes), is able to exert
      its therapeutic activity while circulating in the organism, regardless of the
      integrity of the liposomes. Ac-SOD-enzymosomes have a more rapid antiinflammatory
      effect than SOD liposomes, confirming that the release of Ac-SOD from liposomes
      is no longer required to achieve dismutation. Different methodologies for the
      preparation of SOD and Ac-SOD liposomal formulations (conventional and long
      circulating) have been established and are described in detail here.

PMID- 15721395
TI  - Cryoelectron microscopy of liposomes.
AB  - A thin aqueous film of suspended lipid vesicles?micelles is the object of choice
      for vitrification and subsequent study by cryoelectron microscopy. Just prior to
      vitrification, a thin film (compare with a soap film) is vulnerable to heat and
      mass exchange. Preparation of thin films in a temperature- and humidity
      controlled environment is essential to prevent osmotic and temperature-induced
      alterations of the lipid structure, as will be explained in this chapter. Further
      automation of the preparative procedure by automatic blotting and PC control over
      the timing of critical steps (including vitrification) may further assist in the
      reproducible throughput of high-quality specimens. By cryotomography, taking a
      tilt series under low-dose conditions, a three-dimensional reconstruction of the
      specimen can be analyzed.

PMID- 15721397
TI  - Serous EIC as an early form of uterine papillary serous carcinoma: recent
      progress in understanding its pathogenesis and current opinions regarding
      pathologic and clinical management.

PMID- 15721396
TI  - An evidence-based approach to test accuracy studies in gynecologic oncology: the
      'STARD' checklist.

PMID- 15721398
TI  - Cancer risk associated with early and late maternal age at first birth.
AB  - OBJECTIVE: This paper provides a review of the literature associating maternal
      age at first birth and cancer. Potential mechanisms explaining associations
      between maternal age at first birth and cancer are also discussed. METHOD:
      Systematic review of English language literature using searches on established
      databases (e.g., Medline, Popline) and the references of materials identified in
      these databases. RESULTS: Older age (typically defined as 35 years or older) at
      first birth is associated with increased risk of breast and brain cancers.
      Conversely, younger age (typically defined as 19 years or younger) at first birth
      is associated with an increased risk of cervical and endometrial cancers. There
      is an unclear correlation between maternal age at first birth and site-specific
      malignancies such as ovarian, colorectal, thyroid, pancreatic, and kidney
      cancers. Causal mechanisms linking age at first birth and cancer were identified
      and reported for breast, brain, cervical, and endometrial cancers. CONCLUSION:
      Older age at first birth increases the risk for breast and brain cancers but
      decreases the risk of cervical and endometrial cancers.

PMID- 15721399
TI  - Endometrial cancer: can nodal status be predicted with curettage?
AB  - OBJECTIVE: To determine whether histologic or molecular markers assessed in
      pretreatment curettage specimens predict nodal metastasis in endometrial cancer.
      METHODS: Phenotypic and molecular variables (ploidy, proliferating cell nuclear
      antigen, MIB-1, p53, HER-2/neu, and bcl-2) were analyzed in preoperative
      specimens from 82 patients with endometrial cancer who had lymph nodes dissected.
      These 82 patients had been selected from a total population of 283 patients with
      endometrial cancer, using a case-cohort design. Weighted logistic regressions
      were then used to determine significant predictors of positive lymph nodes, and
      results were estimated for the total population of 283 patients. RESULTS: Of the
      overall population, 12% of patients were estimated to have positive lymph nodes.
      Histologic subtype, p53, and bcl-2 each were significantly correlated (P <0.05)
      with lymph node status. With application of stepwise logistic regression, p53 was
      the only independent predictor of lymph node status. In addition, a statistical
      model predictive of positive lymph nodes was generated which incorporated the
      risk factors p53, bcl-2, and histologic subtype. CONCLUSION: In pretreatment
      curettage specimens, the presence of unfavorable levels of p53 or bcl-2 or of
      nonendometrioid histologic features, or combinations of those, significantly
      predicted lymph node status, thus facilitating the preoperative identification of
      patients at risk of lymph node metastases.

PMID- 15721400
TI  - Opposite alterations of DNA methyltransferase gene expression in endometrioid and
      serous endometrial cancers.
AB  - OBJECTIVE: To examine the DNA methyltransferase (DNMT) mRNA and protein levels in
      endometrioid and serous cancers and to study the relationship between DNA
      methyltransferase expression and endometrial cancer development. METHODS: Normal
      endometrium, Grade I and Grade III endometrioid carcinoma tissues and cell lines,
      as well as serous cancer tissues, were analyzed for DNMT expression. Real-time
      PCR and Western blot techniques were employed to measure the mRNA and protein
      levels of the four DNA methyltransferases, DNMT1, DNMT2, DNMT3A, and DNMT3B.
      Immunohistochemistry was performed to detect alterations in DNMT nuclear
      localization and spatial organization patterns. RESULTS: While DNMT2 and DNMT3A
      expression appear to be normal, two- to fourfold increase in DNMT1 and DNMT3B
      were found in both Grade I and Grade III endometrioid cancers. In addition, the
      poorly differentiated cell lines expressed relatively higher DNMT levels than
      well-differentiated cells. In contrast to endometrioid carcinomas, serous cancers
      expressed substantially lower levels of DNMT1 and DNMT3B than normal controls,
      with four- and twofold reduction observed in DNMT1 and DNMT3B mRNA levels,
      respectively. Western blot analysis confirmed opposite expression patterns of
      DNMT1 and DNMT3B protein in endometrioid and serous cancers. Immunohistochemistry
      showed normal nuclear localization of DNMT1 and DNMT3B in Type I and Type II
      cancer specimens as well as cell cultures. CONCLUSION: Two opposite DNMT
      expression patterns were identified in endometrioid and serous cancers. The
      concerted upregulation in maintenance and de novo DNA methyltransferases in
      endometrioid carcinomas is consistent with a tendency for gene-specific
      hypermethylation observed in this histologic subtype, and may be implicated in
      tumor suppressor silencing. In contrast, the downregulation of maintenance and de
      novo DNA methyltransferases in serous cancers suggests that these tumors may
      contain hypomethylated genomic DNA, which has been associated with a higher
      mutation rate and is consistent with the known pathogenesis of serous-specific
      phenotypes. Taken together, the data suggest that divergent DNA methylation
      pathways may be implicated in the development of Type I and Type II endometrial
      cancers.

PMID- 15721401
TI  - Paclitaxel and carboplatin with amifostine in advanced, recurrent, or refractory
      endometrial adenocarcinoma: a phase II study of the Southwest Oncology Group.
AB  - OBJECTIVES: To evaluate the response rate and progression free and overall
      survival of patients with advanced endometrial cancer treated with paclitaxel,
      carboplatin and amifostine. To evaluate the toxicity of amifostine when used in
      combination with carboplatin and paclitaxel. METHODS: Forty-seven eligible
      patients (median age: 66; range 45-82) with bidimensionally measurable advanced,
      recurrent, or refractory endometrial cancer were treated with carboplatin (AUC =
      6), paclitaxel (175 mg/M2) and amifostine (740 mg/M2) every 4 weeks for 6 cycles
      or until disease progression or unacceptable toxicity. RESULTS: There were 4 CRs
      (8%) (2 confirmed, 2 unconfirmed) and 15 PRs (32%) (9 confirmed, 6 unconfirmed)
      for a total response rate of 40% (95% confidence interval [CI], 26% to 56%). The
      median progression-free survival (PFS) was 7 months (95% CI, 6-9 months) and a 6
      month PFS rate of 64% (95% CI, 50% to 78%). The median overall survival was 14
      months (95% CI, 12 to 17 months). Toxicity was tolerable. While 79% of patients
      developed Grade 3/4 neutropenia (30% Grade 3, 49% Grade 4), there were no
      episodes of Grade 4 febrile neutropenia and one episode of infection with grades
      3-4 neutropenia. CONCLUSION: The combination of paclitaxel and carboplatin with
      amifostine was well reasonably tolerated in this cohort. The regimen demonstrated
      significant activity in endometrial cancer, comparable to other multi-agent
      chemotherapy programs in terms of response rate and survival, and with a
      favorable toxicity profile.

PMID- 15721402
TI  - Relapse rate of patients with low-risk gestational trophoblastic tumor initially
      treated with single-agent chemotherapy.
AB  - OBJECTIVE: To determine the factors for relapse in patients with low-risk
      gestational trophoblastic tumor (GTT) treated with single-agent chemotherapy.
      METHODS: Between 1974 and 2000, 272 consecutive patients with low-risk GTT were
      initially treated with methotrexate (MTX), actinomycin D (Act-D) or etoposide
      chemotherapy. The primary remission rate, change of chemotherapy because of drug
      resistance or toxicity, and relapse rate were compared. RESULTS: Overall survival
      rate and primary remission rate for 272 patients were 100% and 75.7%,
      respectively. Primary remission rate was significantly higher in patients given
      etoposide than those given conventional MTX (P < 0.0001) or MTX-folinic acid (MTX
      CF) (P = 0.0005). Twenty-four (8.8%) patients required a change of chemotherapy
      because of drug resistance. The frequency of drug resistance was significantly
      higher in patients treated with MTX-CF than those treated with etoposide (P =
      0.006). Although maternal age, presence of metastasis, high pretreatment hCG
      titer, and planned hysterectomy did not influence the development of drug
      resistance, the new FIGO scores were significantly higher in patients who
      developed drug resistance. Relapse rate increased significantly in patients who
      had high FIGO scores and who required change of chemotherapy due to drug
      resistance. CONCLUSIONS: All patients with low-risk GTT eventually attained
      complete remission, even though some developed drug resistance to the first-line
      chemotherapy. The relapse rate was significantly higher in patients with drug
      resistance than those with primary remission. Chemotherapy regimen that induces
      little drug resistance is desirable from the viewpoint of long-term prognosis.

PMID- 15721403
TI  - New approaches to pathogenic gene function discovery with human squamous cell
      cervical carcinoma by gene ontology.
AB  - PURPOSE: This study utilized mRNA differential display and the Gene Ontology (GO)
      analysis to characterize the multiple interactions of a number of genes with gene
      expression profile involved in squamous cell cervical carcinoma. METHODS: mRNA
      differential displays were used to identify potential transcripts that were
      differentially expressed between cervix cancers of 13 patients (invasive cancer
      stages Ib-IIb) and universal reference RNAs comprised of 17 different normal
      cervixes. Aberrant bands were excised and used to make cDNA, which was sequenced.
      DNA sequences were compared to other nucleic acids in the NCBR database for
      homology. Transcript expression was verified in select samples using RT-PCR and
      North blotting. The specific functions were correlated with gene expression
      patterns via gene ontology. RESULTS: Fifty-eight genes were up- or down-regulated
      above 2-fold and organized into reciprocally dependent sub-function sets
      depending on the cervical cancer pathway. The GO analysis showed that squamous
      cell cervical carcinogenesis underwent complete up-regulation of cell cycle,
      transport, epidermal differentiation, protein biosynthesis, and RNA metabolism.
      Also, genes belonging to protein metabolism and catabolism activity were
      significantly up-regulated. In contrast, significant down-regulation was shown in
      muscle development, cell adhesion, and damaged DNA binding activity. CONCLUSION:
      The GO analysis can overcome the complexity of the gene expression profile of the
      squamous cell cervical carcinoma-associated pathway and identify several cancer
      specific cellular processes as well as genes of unknown function. Also, GO
      analysis can serve as a powerful basis for a molecular classification of
      carcinogenesis.

PMID- 15721404
TI  - Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or
      II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic
      Oncology Group study.
AB  - OBJECTIVES: To determine progression-free survival (PFS) and overall survival
      (OS) in women with completely resected stage I or II carcinosarcoma of the uterus
      treated with adjuvant ifosfamide and cisplatin, and to assess the toxicity of
      this regimen. METHODS: Eligible patients had histologically confirmed
      carcinosarcoma (mixed mesodermal tumor) and no postoperative radiotherapy
      following complete resection for clinical stage I or II disease. They were to
      have adequate renal, hepatic, and hematologic functions and performance status of
      2 or less. Study entry was to be within 8 weeks of hysterectomy. Patients with
      previous chemotherapy, or other noncutaneous malignancies, were ineligible.
      Ifosfamide was administered 1.5 g/m2 intravenously (IV) over 1 h and cisplatin
      was given 20 mg/m(2) over 15 min followed by mesna 120 mg/m2 IV bolus, then 1.5
      g/m2/24 h as a continuous infusion. Initial doses (daily x 5 every 21 days x 3
      cycles) were reduced by 20% (to 4 days) for myelotoxicity. RESULTS: Nine of
      seventy-six patients enrolled were deemed ineligible and another two who did not
      receive protocol treatment were inevaluable. Of the 65 evaluable patients, median
      age was 65 years; 50 patients (77%) were stage I and 15 (23%) were stage II. PFS
      and OS, respectively, were 69% and 82% at 24 months, and 54% and 52% at 84
      months. Overall 5-year survival was 62%. Leukopenia was the most commonly
      reported, but manageable, toxicity. CONCLUSION: Adjuvant ifosfamide and cisplatin
      after primary surgery for stage I or II carcinosarcoma of the uterus is
      tolerable. In the absence of concurrent controls, the impact on PFS and OS is
      unclear. Pelvic relapse remains problematic.

PMID- 15721405
TI  - Utility and limitations of abdominal radiotherapy in the management of
      endometrial carcinomas.
AB  - OBJECTIVE: The present review analyzes long-term survival, recurrence sites, and
      toxicity in women with peritoneal spread of endometrial treated with abdominal
      radiotherapy, in order to provide therapeutic options as a function of disease
      spread and histology. METHODS: Retrospective medical record review was performed
      of 86 patients receiving abdominal radiotherapy for endometrial carcinomas from
      1975 to 1995 at the University of Minnesota. RESULTS: FIGO stage distribution was
      54 stage IIIA, 2 stage IIIB, 11 stage IIIC, and 19 stage IVB. Disease-free
      survivals were 55% at 5 years, 46% at 10 years, and 36% at 20 years. Recurrence
      rates were 16% for stage IIIA with one peritoneal site, 48% for stage IIIA with
      multiple peritoneal sites or stage IIIB or stage IIIC, and 72% for stage IVB.
      With univariate analysis, statistical significance was found for stage, gross
      peritoneal disease, nodal metastases, histology, concurrent chemotherapy,
      isolated adnexal spread, grade, angiolymphatic invasion, myometrial invasion, and
      age. Multivariate analysis found only stage, histology, and age to be
      significant. Most recurrences were pulmonary or peritoneal. Acute toxicity was
      acceptable. Six percent of patients required surgical intervention for small
      bowel obstructions. CONCLUSIONS: Abdominal radiotherapy confers an excellent
      prognosis for women with stage IIIA cancers with one site of peritoneal
      involvement. Lack of randomized trials makes definitive treatment recommendations
      difficult to provide. Results are less optimal with multiple peritoneal sites of
      involvement, gross peritoneal spread, or papillary serous/clear cell pathology
      but a substantial number of such women can be cured as well.

PMID- 15721406
TI  - Gene therapy of adenovirus mediated CD ::upp/5-FC directed by GSTP1 promoter in
      cisplatin-resistant ovarian cancer.
AB  - PURPOSE: To evaluate the specific killing effect of the adenoviral vector in
      which CD ::upp genes were directed by the GSTP1 promoter on cisplatin-resistant
      ovarian cancer cells. EXPERIMENTAL DESIGN: Cisplatin-sensitive (A2780) and
      cisplatin-resistant (AD6) ovarian cancer cells were infected with recombinant
      adenoviral plasmid carrying the CD ::upp gene driven by the GSTP1 promoter and
      followed with 5-FC administration. RESULTS: In vitro, when MOI was 100 and 5-FC
      was 250 microg/ml, relative survival rate of the AD6 cells was only 3.63 +/-
      1.01%, while under the same conditions, A2780 cells were 76.50 +/- 2.81%.
      Significant bystander effect was caused by the CD ::upp gene and 20% of gene
      transferred AD6 cells caused death to 80.3% of the total cells. Furthermore, a
      significant anti-tumor effect of the Ad.GST-CD ::upp/5-FC was observed in nude
      mice bearing tumors of AD6 cells. CONCLUSIONS: These results indicated that
      adenovirus-mediated Ad.GST-CD ::upp/5-FC directed by GSTP1 promoter is an
      effective approach to overcome cisplatin-resistant ovarian cancer.

PMID- 15721407
TI  - Lymph-vascular space invasion and number of positive para-aortic node groups
      predict survival in node-positive patients with endometrial cancer.
AB  - OBJECTIVE: The aim of this study was to determine pathologic variables associated
      with disease-specific survival of node-positive patients with endometrial
      carcinoma treated with combination of surgery including pelvic and para-aortic
      lymphadenectomy and adjuvant chemotherapy. METHODS: Survival of 55 node-positive
      endometrial carcinoma patients prospectively treated with surgery and adjuvant
      chemotherapy between 1982 and 2002 at Hokkaido University Hospital was compared
      to various histopathologic variables. All patients underwent primary surgical
      treatment including pelvic and para-aortic lymphadenectomy followed by adjuvant
      chemotherapy consisting of intravenous cisplatin, doxorubicin, and
      cyclophosphamide. Survival analyses were performed by the Kaplan-Meier curves and
      the log-rank test. Independent prognostic factors were determined by multivariate
      Cox regression analysis using a forward stepwise selection. RESULTS: Among 303
      consecutive endometrial cancer patients treated during the period of this study,
      55 patients (18.2%), including 44 without peritoneal metastasis (FIGO stage IIIc)
      and 11 with peritoneal metastasis (FIGO stage IV), were found to have
      retroperitoneal lymph node metastasis. Multivariate Cox regression analysis
      revealed that peritoneal metastasis and lymph-vascular space invasion (LVSI) were
      independently related to poor survival in node-positive endometrial carcinoma.
      The estimated 5-year survival rate of stage IIIc patients with or without
      moderate/prominent LVSI was 50.9% and 93.3%, respectively with statistically
      significant difference (P=0.0024). The estimated 5-year survival rate of stage IV
      patients was 20.0%. Prognosis of stage IIIc patients could be stratified into
      three groups by the number of positive para-aortic node (PAN) with an estimated 5
      year survival rate of 86.4% for no positive PAN (n = 23), 60.4% for one positive
      PAN (n = 13), and 20.0% for > or = 2 positive PAN (n = 8). The difference of
      survival rate between no or one positive PAN and > or = 2 positive PAN was
      statistically significant (P = 0.0007 for no positive PAN vs > or = 2 positive
      PAN, P = 0.0319 for one positive PAN vs > or = 2 positive PAN). Multivariate
      analysis including number of positive PAN groups showed that LVSI, number of
      positive PAN groups were independent prognostic factors for survival. Survival of
      patients with stage IIIc disease could be stratified into three groups by
      combination of LVSI and number of positive PAN groups with an estimated 5-year
      survival rate of 93.3% for no or one positive PAN group with nil or minimal LVSI,
      62.6% for no or one positive PAN group with intermediate or prominent LVSI, and
      20.0% for > or = 2 positive PAN groups irrespective of LVSI (P = 0.0002 for no or
      one positive PAN group with nil or minimal LVSI vs > or = 2 positive PAN groups,
      P = 0.0223 for no or one positive PAN group with nil or minimal LVSI vs no or one
      positive PAN group with intermediate or prominent LVSI, P = 0.0388 for no or one
      positive PAN group with intermediate or prominent LVSI vs > or = 2 positive PAN
      groups). CONCLUSIONS: LVSI and number of positive PAN groups were independent
      prognostic factors for stage IIIc endometrial cancer patients. Postoperative
      therapy and follow-up modality need to be individualized according to LVSI and
      the number of positive PAN for stage IIIc patients. New molecular markers to
      predict the prognosis of endometrial cancer patients preoperatively should be
      found for individualization of treatment. New chemotherapy regimen including
      taxane needs to be considered as an adjuvant therapy for patients with node
      positive endometrial cancer.

PMID- 15721408
TI  - Evaluation of patients after extraperitoneal lymph node dissection for cervical
      cancer.
AB  - OBJECTIVE: The presence of nodal metastases is an important prognostic factor in
      patients with cervical cancer. To adjust our therapy to the anatomic extent of
      the disease, we performed a surgical staging with extraperitoneal lymph node
      dissection (EPLND). The goal of our study was to evaluate the clinical outcome
      and side effects of the combined treatment approach of EPLND and either radical
      hysterectomy in case of early stage cervical cancer (FIGO Ia/b and IIa) and
      negative nodes, or pelvic radiotherapy/extended field radiotherapy with
      concomitant chemotherapy in case of positive nodes or advanced stage cervical
      cancer (FIGO IIb, III, and IVa). PATIENTS AND METHODS: Fifty-nine patients with
      primarily diagnosed invasive cervical cancer underwent EPLND. The value of this
      procedure as a diagnostic tool for evaluating the extent of disease was
      determined. Additionally, treatment-related complications and clinical outcomes
      were monitored. RESULTS: A total of 983 lymph nodes were removed during EPLND
      (mean 16.7). According to the results of EPLND, radical hysterectomy was
      abandoned due to histopathologically confirmed lymph node involvement by frozen
      section in 11 out of 36 patients with early stage cervical cancer (31%). The most
      common adverse effects directly related to surgery in general (EPLND or combined
      EPLND and radical hysterectomy) were lymph cysts in seven patients (12%). Only in
      the group of patients who received EPLND followed by radical hysterectomy, 2 out
      of 25 patients (8%) developed a severe ileus postoperatively (WHO Grade 3
      toxicity). The treatment approach of combined EPLND followed by radio- and
      chemotherapy was without major complications (WHO Grade 3 or 4 toxicity). After a
      mean follow up of 28 months (range 6-60), 44 out of 58 patients (one patient lost
      to follow up) are without evidence of disease (76%), 2 patients have progressive
      disease (3%), and 12 patients died of their disease (21%). Using Kaplan-Meier
      analysis, the estimated 5-year overall survival rate for all patients is 64% (SD
      +/- 9%). Performing the Cox proportional regression analysis, in contrast to
      clinical FIGO staging (P = 0.24; ns), lymph node involvement was the only
      significant independent predictor for overall survival (P = 0.04). CONCLUSION:
      Our data support the approach of pretherapeutic surgical staging by performing
      EPLND as a diagnostic tool with a low complication rate. This allows an
      individualized treatment for cervical cancer patients.

PMID- 15721410
TI  - Expression of progesterone receptor is a favorable prognostic marker in ovarian
      cancer.
AB  - OBJECTIVE: Receptors for estrogen (ER), progesterone (PR), or androgen (AR) are
      predictive and prognostic markers of malignancy of multiple endocrine organs,
      including endometrial and breast cancer. However, the role of ERs, PRs, or ARs in
      the carcinogenesis of ovarian cancer, another sex hormone-dependent malignancy,
      is still controversial despite numerous studies that have attempted to determine
      their role. The disagreement in the findings may result from the fact that the
      numbers of tumor samples in studies have been small and that different
      immunohistochemical methods have been used that can introduce variation in the
      scoring of the histology. We therefore examined the pattern of expression of ERs,
      PRs, and ARs in a large number of samples of primary ovarian carcinoma by using a
      tissue microarray technique. METHODS: We constructed a tissue microarray with 322
      samples of primary ovarian carcinoma obtained at surgery performed at The
      University of Texas M. D. Anderson Cancer Center between 1990 and 2000.
      Immunohistochemistry studies were performed by using the immunoperoxidase
      technique against primary antibodies (ER, PR, and AR). RESULTS: ERs, PRs, and ARs
      were differently expressed in different histotypes of ovarian cancer: ERs were
      expressed in 77.3% of all cases but more highly expressed in serous and
      endometrioid types; PRs were expressed in 26.2% of all cases but most highly
      expressed in the endometrioid type < 64.2%; and ARs were expressed in 43.7% of
      all cases but were most highly expressed in serous (47.5%) carcinomas. Of
      particular importance, the expression of PRs, but not ERs or ARs, was associated
      with better survival (P < 0.0001) in univariate and multivariate analyses.
      CONCLUSIONS: The PR is an independent marker, with its overexpression associated
      with a favorable prognosis in women with ovarian cancer.

PMID- 15721409
TI  - Concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy for
      uterine cervical cancer.
AB  - OBJECTIVE: We retrospectively reviewed our experience with concurrent
      chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR
      ICBT) to assess its feasibility and efficacy in the treatment of patients with
      uterine cervical cancer. METHODS: Forty patients with uterine cervical squamous
      cell carcinoma treated with CCRT using HDR-ICBT were analyzed. The median
      cervical tumor size assessed by MRI was 63 mm (range: 40-86 mm). Eighteen
      patients (45%) had enlarged pelvic nodes on MRI (> or =10 mm). Cisplatin (20
      mg/m2/day) was concurrently administered with radiotherapy for 5 days at 21-day
      intervals for a median of three courses (range: 1-5 courses). Thirty-eight (95%)
      patients received whole pelvic external beam radiotherapy (EBRT) with 40 Gy/20
      fractions followed by HDR-ICBT with 18 Gy/3 fractions to point A. Subsequently,
      additional pelvic EBRT with 10 Gy/5 fractions was delivered with a midline block.
      The cumulative biological effective dose (BED) at point A of this schedule was 77
      Gy10. The median follow-up period for all 40 patients was 37 months (range: 8-71
      months). RESULTS: Grade 3/4 leukopenia was the most common acute side effect
      (83%). The actuarial 3-year pelvic control rate, disease-free survival rate, and
      overall survival rate were 91%, 67%, and 79%, respectively. Eight (20%) patients
      suffered late gastrointestinal complications (all grades). No patient suffered
      radiation cystitis (all grades). Only one patient experienced grade 3
      complication (enterocolitis). The actuarial 3-year late complication rate (all
      grades) was 9% for proctitis and 15% for enterocolitis. CONCLUSION: This
      preliminary study suggests that CCRT using HDR-ICBT is feasible and efficacious
      for patients with locoregionally advanced uterine cervical cancer.

PMID- 15721411
TI  - Effects of prolonged tamoxifen treatment on receptor expression and apoptosis of
      ovarian cancer cells.
AB  - OBJECTIVE: Tamoxifen, which is widely used in the treatment of breast cancer,
      also has a beneficial effect on cisplatin-refractory ovarian cancer. In this
      study, we investigated the long-term effects of this drug on estrogen-receptor
      positive ovarian cancer cells. METHODS: We performed an in vitro selection
      process by long-term treatment of BG-1 ovarian cancer cells with 4-hydroxy
      tamoxifen (4-OH TAM). Drug effects on cell growth were determined by measurement
      of relative cell numbers (MTS assay), the apoptotic effects of 4-OH TAM were
      determined by analysis of poly (ADP-ribose) polymerase (PARP) cleavage and by
      ELISA measurement of DNA-histone complexes in cytoplasm. RESULTS: Analysis of BG
      1(LT) ovarian cancer cells isolated after 5 months of long-term treatment with 4
      OH TAM revealed both a significantly reduced apoptotic and antiproliferative
      effect of this drug. Further experiments to examine expression changes of the
      receptor tyrosine kinases EGFR, HER2 and estrogen receptor alpha did not reveal
      any alterations in BG-1(LT) if compared to wild-type cells. In contrast, in this
      cell line, a significant alteration in the expression of estrogen receptor beta
      was observed. CONCLUSION: Our findings indicate that long-term treatment with 4
      OH TAM is able to diminish both the antiproliferative and apoptotic action of
      this drug on BG-1 ovarian cancer cells. Our data suggest that the responsiveness
      of ovarian cancer cells to 4-OH TAM decreases after long-term treatment with this
      drug in vitro like previously observed after long-term treatment of breast cancer
      cells.

PMID- 15721412
TI  - Distinction between serous tumors of low malignant potential and serous
      carcinomas based on global mRNA expression profiling.
AB  - OBJECTIVES: The molecular pathogenesis of ovarian serous tumors of low malignant
      potential (S-LMP) is not well understood, although the collective data suggest
      that they arise through molecular mechanisms distinct from those leading to
      conventional serous carcinomas (S-Ca). To further examine the molecular
      differences between these two diseases, we studied the gene expression pattern of
      ovarian S-LMP and S-Ca using high-density spotted cDNA and tissue microarrays.
      METHODS: Total RNA from 23 ovarian S-LMP and S-Ca was analyzed on 43,200 spot
      cDNA microarrays and the differential expression of proteins encoded by
      differentially expressed genes was validated using tissue microarrays. RESULTS:
      Unsupervised hierarchical clustering analysis of filtered data showed a complete
      separation between S-LMP and S-Ca, based predominantly on a small set of genes
      expressed at higher levels in S-LMP than in S-Ca. Many genes previously
      identified as up-regulated in ovarian carcinoma relative to normal ovarian tissue
      were expressed at even higher levels in S-LMP. These genes included mucin-1,
      mesothelin, HE4, PAX 8, and apolipoprotein J/clusterin. Immunohistochemical
      staining of tissue microarrays confirmed higher expression of selected proteins
      encoded by these genes in the S-LMP. Few genes were expressed at a higher level
      in S-Ca; these included E2F1, topoisomerase IIalpha, and cyclin E, with higher
      levels of cyclin E protein confirmed by immunohistochemistry. CONCLUSIONS: S-LMP
      and S-Ca are distinguished at the molecular level by a relatively small gene set,
      suggesting the pathogenesis of S-LMP as well as S-Ca may involve molecular
      pathways that escape detection by global gene expression profiling. In order to
      obtain biologically and clinically relevant information about the mechanisms
      involved in ovarian carcinogenesis, future studies based on molecular profiles of
      ovarian cancer should include analyses of low malignant potential tumors.
      Inclusion of such tumors is also critical to the evaluation of the efficacy of
      potential new diagnostic and/or therapeutic biomarkers.

PMID- 15721414
TI  - Impact of tumor volume-directed involved field radiation therapy integrated in
      the management of recurrent ovarian cancer.
AB  - OBJECTIVES: Assess the role of involved field radiation therapy (IFRT) in
      recurrent ovarian cancer. METHODS: Thirty-five patients with a diagnosis of
      epithelial ovarian cancer received radiation therapy at LUMC between 1991 and
      2001. Of these, 20 received tumor volume-directed IFRT for localized
      extraperitoneal recurrences (either as consolidation following debulking surgery
      or as attempted salvage if unresectable) and form the basis of this report. All
      patients were heavily pretreated with multiple chemotherapy regimens. Eleven
      patients had optimal debulking of their recurrences prior to radiation. IFRT was
      primarily with external beam (median dose 50.4 Gy). Appropriate statistical
      analyses evaluated association among disease-free (DFS), overall survival (OS),
      local recurrence-free (LRFS), and various prognostic factors. LRFS was defined as
      freedom from in-field recurrences and was considered as a measure of
      effectiveness of radiotherapy. RESULTS: Of 20 patients, 17 had a complete
      response after RT. The actuarial LRFS, OS, and DFS at 5 years from date of
      radiation were 66%, 34%, and 34%, respectively. The LRFS at 3 years was 89% for
      those with optimal resection vs. 42% for those with gross residual/unresectable
      tumor, which was significantly better (P = 0.04). The corresponding 3-year DFS
      was 72% vs. 22% and 5-year OS was 50% vs. 19%, respectively. Acute complication
      of RT was mild, half had Grade 1-2 gastrointestinal (GI) toxicity, three patients
      had Grade 3-4 late GI effects. CONCLUSION: IFRT is effective in controlling
      localized recurrences of ovarian cancer, especially after they are optimally
      debulked (89% local control and 50% 5-year overall survival in this subgroup),
      and is relatively well tolerated in these heavily pretreated patients.

PMID- 15721413
TI  - Human papillomavirus type 16 E2 and E6/E7 variants.
AB  - OBJECTIVES: Polymorphisms in human papillomavirus (HPV) type 16 have been shown
      to be related to geographic areas and are broadly classified as European (E),
      African (Af), Asian (As), or Asian-American (AA). Certain variants have been
      reported as being more likely to cause cervical disease; our objectives were to
      identify new HPV16 polymorphisms, to determine the linkage of the E2 and E6/E7
      regions and to determine the minimum sequence necessary to classify variants.
      METHODS: We sequenced the complete E2, E6, and E7 regions in all HPV16-positive
      cervical samples identified in a case-control study of pre-invasive cervical
      disease. RESULTS: In the 100 samples analyzed, only one new polymorphism was
      identified, a synonymous change, T3205A, in region E2. The frequency distribution
      of variants in the sample set was 37 European prototypes and 27 E-G350, 16 AA, 5
      Af1, 2 Af2, 8 E-C109G, 3 E-G131G, and 2 As. As shown by others, region E7 varied
      much less than E6 and E2. CONCLUSIONS: In each case, E2 changes were linked to
      the expected E6/E7 changes, and there was no evidence for recombination. The
      linkage between E2 and E6/E7 allows variant classification to be based on a short
      E6 sequence (nt 109-350).

PMID- 15721415
TI  - Death receptors and ligands in cervical carcinogenesis: an immunohistochemical
      study.
AB  - OBJECTIVE: Increasing imbalance between proliferation and apoptosis is important
      in cervical carcinogenesis. The death ligands FasL and tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) induce apoptosis by binding to their
      cognate cell-surface death receptors Fas or death receptor (DR) 4 and DR5. This
      study aims to examine if changes in death ligand and death receptor expression
      during different stages of cervical carcinogenesis are related to an imbalance
      between proliferation and apoptosis. METHODS: The immunohistochemical expression
      and localization of Fas/FasL and DR4/DR5/TRAIL were assessed in 11 normal
      cervices, 15 cervical intraepithelial neoplasia (CIN) grade I, 15 CIN II, 13 CIN
      III, and 25 (microinvasive) squamous cell cervical cancers. The number of
      apoptotic cells was determined by morphological criteria and the number of
      proliferating cells by counting Ki-67-positive cells. RESULTS: A marked increase
      in proliferation as well as apoptosis percentage was found with increasing
      severity of neoplasia. In normal cervix and CIN I samples, FasL, DR4, DR5, and
      TRAIL staining was mainly observed in the basal/parabasal layer, whereas Fas
      staining was localized in the superficial, more differentiated epithelial layer.
      Frequency of Fas-positive staining decreased with increasing severity of CIN. In
      contrast, homogeneous FasL, DR4, DR5, and TRAIL expression throughout the lesions
      was more frequently observed in CIN III and cervical cancer. FasL, DR4, DR5, and
      TRAIL staining patterns were correlated, although TRAIL expression was more
      intense in low-grade lesions. No association was found between death receptor or
      ligand expression with the percentage of apoptosis or proliferation. CONCLUSION:
      The loss of Fas and the deregulation of FasL, DR4, DR5, and TRAIL in the CIN
      cervical cancer sequence suggest a possible functional role of these death
      ligands and receptors during cervical carcinogenesis. The frequent expression of
      DR4 and DR5 presents these receptors as promising targets for innovative therapy
      modalities in cervical cancer.

PMID- 15721416
TI  - Human papillomavirus testing for primary screening in women at low risk of
      developing cervical cancer. The Greek experience.
AB  - OBJECTIVE: To compare the performance of human papillomavirus (HPV) DNA detection
      against routine Papanicolaou smear for the detection of low- and high-grade
      cervical intraepithelial neoplasia in a low-risk population. MATERIALS AND
      METHODS: A cross-sectional study was performed involving 1296 women attending six
      outpatient clinics in Northern Greece (Thessaloniki, Thermi, Mihaniona, Corfu,
      Veria, and Serres). Women underwent a gynecological examination, including
      collection of exfoliated cervical cells for Papanicolaou cytology and HPV DNA
      detection. Cytology was processed according the conventional routine manner, and
      HPV DNA was determined using the polymerase chain reaction technique. In positive
      cases of either method, a complete colposcopic evaluation was performed with
      directed biopsies. Tests (HPV DNA, cytology, and colposcopy) performance
      characteristics were determined using the histopathologic diagnosis as the
      reference standard. RESULTS: HPV DNA testing showed a significantly better
      sensitivity than the Papanicolaou smear in detecting cervical intraepithelial
      neoplasia (75% versus 50% for high-grade lesions and 81.2% versus 50% for lesions
      of any grade, respectively). Specificity, and positive and negative predictive
      values did not significantly differ. Even after dividing women in younger or
      older than 30 years, the sensitivity of the HPV DNA test was greater than
      cytology (100% and 70% versus 50% for cytology in both groups, respectively),
      with a 6.3% loss in specificity when performed in women younger than 30 years.
      CONCLUSION: HPV testing could be useful in screening women at low risk for
      cervical cancer, either as an adjunct tool to augment existing cytology programs
      or as a unique test of its own.

PMID- 15721417
TI  - Rethinking the use of radiation and chemotherapy after radical hysterectomy: a
      clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology
      Group/Radiation Therapy Oncology Group trial.
AB  - OBJECTIVE: To retrospectively analyze data from a previously reported randomized
      trial of either pelvic radiation (RT) or RT + chemotherapy (CT) in patients
      undergoing radical hysterectomy and pelvic lymphadenectomy with positive pelvic
      lymph nodes, parametrial involvement, or surgical margins; to explore
      associations between RT + CT; and to investigate histopathologic and clinical
      factors which might be predictive of recurrence. METHODS: Histopathologic
      sections from biopsies and hysterectomies and clinical data were reviewed from
      patients with stage IA2, IB, or IIA cervical cancer treated with RT or RT + CT
      (cisplatin 70 mg/m2 plus fluorouracil 1000 mg/m2 every 3 weeks for four cycles).
      A univariate analysis was performed because the relatively small sample size
      limited the interpretation of a multivariate analysis. RESULTS: Of the 268
      enrolled women, 243 (RT = 116; RT + CT = 127) were evaluable. The beneficial
      effect of adjuvant CT was not strongly associated with patient age, histological
      type, or tumor grade. The prognostic significance of histological type, tumor
      size, number of positive nodes, and parametrial extension in the RT group was
      less apparent when CT was added. The absolute improvement in 5-year survival for
      adjuvant CT in patients with tumors < or =2 cm was only 5% (77% versus 82%),
      while for those with tumors >2 cm it was 19% (58% versus 77%). Similarly, the
      absolute 5-year survival benefit was less evident among patients with one nodal
      metastasis (79% versus 83%) than when at least two nodes were positive (55%
      versus 75%). CONCLUSIONS: In this exploratory, hypothesis-generating analysis,
      adding CT to RT after radical hysterectomy, appears to provide a smaller absolute
      benefit when only one node is positive or when the tumor size is < 2 cm. Further
      study of the role of CT after radical hysterectomy in patients with a low risk of
      recurrence may be warranted.

PMID- 15721418
TI  - Role of laparoscopy to assess the chance of optimal cytoreductive surgery in
      advanced ovarian cancer: a pilot study.
AB  - OBJECTIVE: To investigate whether laparoscopy can be considered as adequate and
      reliable as standard laparotomy in predicting optimal cytoreduction (RT < or = 1
      cm) in patients with advanced ovarian cancer. METHODS: From March to November
      2003, 95 patients with suspected advanced ovarian or peritoneal cancer have been
      evaluated. Thirty-one cases were excluded due to an anesthesiological class of
      risk ASA III-IV (51.6%) and for the presence of a large size mass reaching the
      xiphoid (48.4%). Sixty-four patients completed the study. All patients were
      submitted to preoperative clinico-radiological evaluation and then to both
      laparoscopy and standard longitudinal laparotomy, sequentially. Some specific
      preoperatively defined parameters were analyzed during each procedure in order to
      obtain the most accurate evaluation on the possibility to get an optimal
      cytoreduction. RESULTS: The overall accuracy rate of laparoscopy in assessing
      optimal cytoreduction was 90%. The negative predictive value (NPV) of the
      clinical-radiologic evaluation corresponded to 73%, whereas in no case was the
      judgment of unresectable disease obtained by laparoscopy changed by the
      laparotomic approach (NPV 100%). On the contrary, an optimal debulking was
      achievable in 34 of 39 cases (87%) selected as completely resectable by
      explorative laparoscopy. CONCLUSIONS: Laparoscopy can be considered super
      imposable to standard longitudinal laparotomy in identifying not optimally
      resectable advanced ovarian cancer patients.

PMID- 15721419
TI  - Glutathione-S-transferase and p53 polymorphisms in cervical carcinogenesis.
AB  - OBJECTIVE: To investigate the clinical significance of glutathione-S-transferase
      GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis. METHODS:
      GSTM1, GSTT1 and p53 codon 72 polymorphisms together with human papillomavirus
      (HPV) types were examined in a total of 198 cervical smear samples using
      multiplex polymerase chain reaction (PCR) and PCR restriction fragment length
      polymorphism (RFLP) techniques. RESULTS: Forty-two patients with high-grade
      squamous intraepithelial lesion (HSIL) had higher frequency of high-risk HPV and
      null GSTT1 genotype than 102 with low-grade SIL (LSIL) and 54 controls. Thirty
      one patients with HSIL had also statistically higher frequency of null GSTT1
      genotype than 28 with LSIL among 69 patients with high-risk HPV. There was no
      statistical difference in p53 Arg, Arg/Pro and Pro genotypes between SILs and
      controls with or without high-risk HPV. CONCLUSION: GSTT1 null genotype in
      cervical cell samples may be associated with more severe precancerous lesions of
      the cervix in a Japanese population. The p53 codon 72 polymorphism is unlikely to
      be related to HPV status and the onset of cervical cancer.

PMID- 15721420
TI  - Pre-operative imaging, surgery and adjuvant therapy for women diagnosed with
      cancer of the corpus uteri in community practice in the United States.
AB  - INTRODUCTION: Non-Hispanic black women are less often diagnosed with endometrial
      cancer than are non-Hispanic white women, but are more likely to die of their
      disease. Reasons for this disparity in outcome are not well understood. METHODS:
      The Surveillance, Epidemiology, and End-Results Program data were used to sample
      women newly diagnosed in 1998 with cancer of the corpus uteri. A total of 711
      women with no previous diagnosis of cancer were selected. Women with sarcoma were
      not eligible for the study. We then sought to verify the therapy provided each
      woman with her treating physician. RESULTS: Non-Hispanic black women were
      diagnosed with higher stage, grade, poor histologic subtype, and greater
      extension of the tumor than were non-Hispanic white women. Hispanic women were
      diagnosed with more favorable tumor characteristics than non-Hispanic black
      women, but less favorable than non-Hispanic white women. The use of radiation and
      chemotherapy increased with stage. CONCLUSIONS: Our study did not show any
      difference in recommended therapy for women with uterine adenocarcinoma among NH
      black women, NH white women, and Hispanic women. We must look for other factors,
      therefore, to explain the disparities in cancer outcome observed among NH black
      women with endometrial cancer.

PMID- 15721421
TI  - Phase II evaluation of liposomal doxorubicin (Doxil) in recurrent or advanced
      leiomyosarcoma of the uterus: a Gynecologic Oncology Group study.
AB  - OBJECTIVE: This is a phase II group-wide study of liposomal doxorubicin
      chemotherapy in patients with advanced or recurrent uterine leiomyosarcomas. The
      aim was to evaluate clinical response and toxicity. METHODS: Patients with
      histologically confirmed persistent or recurrent leiomyosarcomas of the uterus
      with documented disease progression after appropriate local therapy were invited
      to participate in this study. Bidimensionally measurable disease, GOG performance
      status of 0, 1, or 2 (Karnofsky 80-100) was required; all patients must have
      failed local therapeutic measures and be considered incurable. Other eligibility
      criteria included adequate hepatic, renal, and hematologic function. Patients
      were ineligible if they had received previous chemotherapy or had other
      noncutaneous malignancies. Patients received liposomal doxorubicin 50 mg/m2 IV
      over 1 h. Courses were repeated every 4 weeks until disease progression or
      adverse side effects supervened. RESULTS: Thirty-five patients were entered into
      this study between May 2000 and June 2001. Three patients were determined
      ineligible because of wrong pathological cell type or inadequate pathology
      information and one was inevaluable for lack of data. Median age was 52 years
      (range 36-78 years). GOG performance status was 2 in 1 instance, 1 in 15 cases,
      and 0 in 15 others. Eleven patients (35.5%) had received radiotherapy. A median
      of 2.0 courses was given (range 1-8). Five patients (16.1%) experienced grade 3
      or 4 neutropenia, and seven (22.6%) had grade 3 or 4 anemia. Two patients
      developed grade 3 and one patient developed grade 4 cardiovascular adverse
      events, not necessarily drug related. There were seven cases of grade 3 or 4
      gastrointestinal toxicity and two patients developed grade 3 dermatologic
      toxicity. One complete (3.2%) and four partial (12.9%) responses were reported.
      Ten patients (32.3%) had stable disease, 15 (48.4%) had increasing disease, and
      response could not be assessed in 1 (3.2%). CONCLUSION: The dose and schedule of
      liposomal doxorubicin employed in this trial showed no advantage over historical
      results with doxorubicin in the treatment of uterine leiomyosarcoma.

PMID- 15721422
TI  - Cancer of the uterine corpus among Hispanic women living in the United States:
      patterns of staging, diagnosis, and primary treatment.
AB  - OBJECTIVES: To evaluate the demographic characteristics, clinico-pathological
      features, and patterns of care of uterine cancer among Hispanic women living in
      the United States. METHODS: The National Cancer Institute (NCI)'s Surveillance,
      Epidemiology, and End Results Program (SEER), was used to identify 1618 Hispanic,
      17,814 non-Hispanic white (NHW), and 1477 non-Hispanic black (NHB) women
      diagnosed with primary carcinoma of the uterus during 1996-2000. Data derived
      from hospital registries was analyzed, for differences in case presentation,
      staging, and primary treatment by race/ethnicity and age. Statistical analysis
      was performed using the IBM PC packages, Stata, and the SAS system. RESULTS:
      Hispanic women were statistically significantly more likely to present with
      uterine cancer at a younger age compared to non-Hispanic groups. Hispanic women
      with early stage disease (stage I-II) were also statistically significantly more
      likely to be younger than 55 years at the time of diagnosis (NHW: OR=0.40, 95%
      CI: 0.35-0.45; P = 0.0000, NHB: OR=0.45, 95% CI: 0.38-0.55; P=0.0000). Hispanics
      were statistically significant less likely than NHB to present with advanced
      stage disease, high tumor grade, and receive radiation therapy for uterine
      cancer. CONCLUSIONS: Hispanic women are more likely to be diagnosed with uterine
      cancer at a younger age than other ethnic groups. The etiologic factors related
      to this presentation have yet to be precisely defined. Additional epidemiological
      and demographic studies, addressing such factors as body mass index and other
      medical co-morbidities, are needed to identify opportunities for improved cancer
      prevention and control in this population of women.

PMID- 15721423
TI  - Protective role of the polymorphism CCR2-64I in the progression from squamous
      intraepithelial lesions to invasive cervical carcinoma.
AB  - OBJECTIVE: Invasive cervical cancer (ICC) is one of the most common malignant
      diseases among women, representing almost 10% of all the cancers in the female
      population. The aim of this study was to explore the association of the CCR2-64I
      polymorphism with the risk of developing invasive cervical cancer (ICC) from
      squamous intraepithelial lesions (SILs). METHODS: DNA samples were extracted from
      peripheral blood cells of 109 patients with squamous intraepithelial lesions (28
      low-grade and 81 high-grade cases) and 217 patients with ICC. The CCR2-64I
      polymorphism was analyzed through polymerase chain reaction (PCR)-restriction
      fragment length polymorphism (RFLP) (BseJI). The odds ratio (OR) and its 95%
      confidence interval (CI) were calculated as a measure of the association between
      CCR2-64I genotypes and cervical cancer risk. RESULTS: The frequency of the G/A
      genotype was significantly higher in SIL patients (n = 109) than ICC patients (n
      = 217) (P = 0.005; OR = 0.42; 95% CI: 0.22-0.83). Furthermore, no association was
      found when we analyzed the influence of the A allele in the progression from low
      grade SIL (LSIL) to high-grade SIL (HSIL) (OR = 1.05; 95% CI = 0.370-2.98; P =
      0.930), but a statistically significant association was found in the progression
      from high-grade SIL to ICC (OR = 0.435; 95% CI = 0.222-0.854; P = 0.014).
      CONCLUSION: These findings suggest that CCR2-64I polymorphism might have a
      protective role in the evolution from high-grade SIL to ICC.

PMID- 15721424
TI  - Potential application of the ATP cell viability assay in the measurement of
      intrinsic radiosensitivity in cervical cancer.
AB  - BACKGROUND: Intrinsic radiosensitivity using the clonogenic assay and the cell
      surviving fraction at 2 Gy (SF2) has been shown to be an independent prognostic
      factor for patient response to radiotherapy in carcinoma of the cervix. The
      clonogenic assay has significant shortcomings, making it unsuitable for routine
      clinical use. The ATP cell viability assay (ATP-CVA) has been shown to have a
      high tumor evaluability rate, technical simplicity, and reproducibility in
      chemosensitivity testing. AIMS: This study compares the ATP-CVA with the
      clonogenic assay in the in vitro radiosensitivity testing of cervical cancer cell
      lines. Correlation of in vitro radiosensitivity and in vivo patient response was
      also determined. METHODS: Five cervical carcinoma cell lines (SiHa, HeLa, Caski,
      C-33A, and C4-1) were tested using the ATP-CVA and the clonogenic assay. Survival
      curves were plotted and the mean SF2 values obtained by the two different assay
      methods were compared using ANOVA to see if there were significant differences.
      Mean SF2 values obtained from 27 cervical cancers were compared with clinical
      outcomes. RESULTS: The SF2 values for the cell lines ranged from 0.28 to 0.67
      when tested using the ATP-CVA. Using the clonogenic assay, the SF2 values ranged
      from 0.27 to 0.70. ANOVA with Bonferroni pairwise multiple comparison showed no
      significant difference between the mean SF2 values for the individual cell lines
      between the two assay methods. Twenty-three cervical cancer samples (85%) were
      evaluable for SF2 using ATP-CVA. The mean SF2 values of patients who had
      locoregional failure were significantly higher than those who achieved local
      control (P <0.01). CONCLUSIONS: Testing intrinsic radiosensitivity using the
      surviving fraction at 2 Gy (SF2) is comparable using the two assay methods of ATP
      CVA and clonogenic assay. The ATP-CVA should be further investigated in the
      testing of intrinsic radiosensitivity in patients with cervical cancer.

PMID- 15721425
TI  - Laser CO2 conization in postmenopausal age: risk of cervical stenosis and
      unsatisfactory follow-up.
AB  - OBJECTIVE: To assess chances of adequate cyto-colposcopic follow-up after laser
      conization performed in postmenopausal screening population by the evaluation of
      postoperative cervical stenosis and unsatisfactory colposcopy rates. PATIENTS AND
      METHODS: One thousand two hundred eighteen patients were submitted to laser CO2
      conization for cervical intraepithelial neoplasia (CIN). Incidence and risk
      factors for cervical stenosis and unsatisfactory follow-up were retrospectively
      evaluated comparing fertile with postmenopausal patients. RESULTS: Global
      incidences of postoperative unsatisfactory colposcopy and cervical stenosis were
      46.2% and 7.1%. These rates were higher in postmenopausal patients compared with
      fertile ones, revealing a statistical correlation between unsatisfactory follow
      up and postmenopausal status at the time of conization. Association between CIN
      relapse and cervical stenosis was significantly higher in postmenopausal group
      (66.7% vs. 8.6%; P <0.05), where two cases of recurrence were detected only after
      hysterectomy, because of an insurmountable cervical stenosis. Univariate and
      multivariate analysis revealed HRT use as the only significant factor in
      influencing postoperative cervical stenosis. CONCLUSION: Conization is still
      considered as the standard treatment for CIN at any woman's age, when excisional
      management is indicated, but all postmenopausal patients should be counseled
      about the possibility of postoperative stenosis that could exclude an adequate
      follow-up, configuring a failure of the conservative treatment. HRT use is
      associated with a low risk of stenotic complications; therefore, if possible,
      users should be encouraged to continue therapy at least 1 year after laser
      conization.

PMID- 15721426
TI  - Outcome and prognostic factors in ovarian germ cell malignancies.
AB  - OBJECTIVES: This study was undertaken to investigate the outcome and prognostic
      factors in patients with ovarian germ cell malignancies (OGCMs). METHODS: A total
      of 93 patients with OGCMs were retrospectively reviewed, among whom 84 patients
      had primary treatment at Chang Gung Memorial Hospital (CGMH) between 1984 and
      2003. The other nine patients were primarily treated outside and referred for
      follow-up (n = 1), adjuvant chemotherapy (n = 4), or salvage therapy after
      recurrence (n = 4). The clinicopathological and treatment-related characteristics
      were analyzed for association with the occurrence of tumor persistence/recurrence
      or death. RESULTS: Of the study patients, 32 had dysgerminoma (DSG), 29 immature
      teratoma (IMT), 23 endodermal sinus tumor, 7 mixed germ cell tumors, and 1 each
      had choriocarcinoma and embryonal carcinoma. The median follow-up of survivors
      was 66 months (range, 12-236 months). The median time to recurrence or
      progression was 8 months. There were 11 treatment failures with 6 died of cancer.
      The 5-year survival rate was 97.4% for those primarily treated at CGMH. Histology
      (DSG/IMT versus non-DSG/IMT) (P < 0.0001) and International Federation of
      Gynecology and Obstetrics stage (P = 0.001) were significantly associated with
      treatment failure, while histology (P = 0.0004), salvage high-dose chemotherapy
      (HD-CT) after primary chemotherapy failed (P = 0.0405), and residual tumor after
      salvage surgery (P = 0.0014) were significant prognostic factors for overall
      survival. CONCLUSIONS: Prognosis of OGCMs is excellent if managed with standard
      treatment initially. Aggressive HD-CT with salvage surgery needs to be applied
      for recurrent/persistent disease after primary chemotherapy.

PMID- 15721427
TI  - Tailoring the parametrectomy in stages IA2-IB1 cervical carcinoma: is it feasible
      and safe?
AB  - OBJECTIVE: Several authors have proposed the use of a less aggressive surgery
      (i.e., modified or type 2 radical hysterectomy) for patients affected by early
      stages cervical carcinoma. However, little attention has been given to the
      evaluation of adverse prognostic factors before selecting the surgical approach.
      The aim of this study is to evaluate the feasibility and safety of tailoring
      parametrectomy on the basis of specific prognostic factors preoperatively
      assessed. METHODS: Patients with cervical carcinoma FIGO IA2-IB1 entered the
      study. Eligibility criteria were: age < 75 years, no contraindications for
      surgery, informed consent, expected cooperation for follow-up. Tumor size was
      preoperatively assessed by pelvic examination under anesthesia and pelvic MRI.
      Patients were submitted to systematic lymphadenectomy of superficial obturator,
      external iliac, and interiliac nodes by laparotomy or laparoscopy. Lymph nodes
      were sent for frozen section. Node-negative patients were submitted to modified
      radical hysterectomy (type 2). Patients with nodal metastases underwent classical
      radical hysterectomy (types 3-4) and systematic pelvic and aortic node dissection
      up to the inferior mesenteric artery. Survival rates were calculated using the
      Kaplan-Meier product-limit method. RESULTS: Eighty-three patients were enrolled
      in the study. Among these, 63 patients were node-negative at frozen section, and
      therefore submitted to modified radical hysterectomy (Group A); 20 patients were
      found having nodal metastases intra-operatively, and therefore submitted to
      classical radical hysterectomy (Group B). Median follow up was 30 months. Five
      years overall survival was 95% for Group A, and 74% for Group B. CONCLUSIONS: Pre
      treatment evaluation of adverse prognostic factors in patients affected by
      cervical cancer FIGO stages IA2-IB1 is feasible and mandatory to determine if a
      less radical surgery is applicable and safe.

PMID- 15721428
TI  - Lymphvascular space involvement: an independent prognostic factor in endometrial
      cancer.
AB  - PURPOSE OF INVESTIGATION: To evaluate whether lymphvascular space involvement
      (LVSI) is a risk factor for relapse of disease and lymph node metastasis in
      endometrial cancer. METHODS: From 1978 till 2003, 609 patients with epithelial
      endometrial cancer were treated at the Groningen University Medical Center. The
      association of LVSI and relapse of disease was evaluated in the total group of
      609 patients and in a 'low' and 'high' risk stage I endometrial cancer group. In
      239 surgically staged patients, the relation of LVSI and lymph node metastasis
      was investigated. RESULTS: The median age at diagnosis was 63 years (range 27-92
      years) with a median follow-up of 58 months (range 0-236 months). More than half
      of the patients (56%) received adjuvant radiotherapy. LVSI was present in 123
      patients (25,6%), and a prognostic factor for relapse of disease (multivariate
      analysis, P < 0.0001). In the 'low' and 'high' risk stage I endometrial cancer
      patients an increase of 2.6 times in relapse of disease was observed in the
      presence of LVSI. LVSI positive tumors were more likely to have metastasized to
      the pelvic lymph nodes (multivariate analysis, P = 0.001). In patients with
      proven negative nodes, LVSI was a prognostic factor for relapse of disease
      (univariate analysis, P = 0.02). CONCLUSION: LVSI is a predictor of nodal disease
      and an independent prognostic factor for relapse of disease in all stages of
      endometrial cancer. Patients with stage I endometrial cancer with positive LVSI
      are at risk for relapse of disease and might therefore benefit from adjuvant
      therapy. CONTENT: The presence of lymphvascular space involvement (LVSI) in
      endometrial cancer is significantly and independently associated with an
      increased risk of pelvic lymph node metastases and/or relapse of disease.

PMID- 15721429
TI  - Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent
      cervix cancer. A pilot study.
AB  - OBJECTIVES: This is a pilot study for a future trial to assess the efficacy and
      safety of combination chemotherapy with docetaxel and carboplatin in advanced or
      recurrent uterine cervix cancer. METHODS: The patients eligible for this study
      had histologically confirmed, advanced (stage IB2-IV) or recurrent uterine cervix
      cancer. Eligible patients had measurable lesions and must have sufficient bone
      marrow, renal, and liver functions. Docetaxel was administered intravenously (IV)
      at 60 mg/m2 followed by IV carboplatin administration based on AUC = 6.
      Chemotherapy was repeated in 1-6 courses depending on the purpose of the therapy.
      The response was evaluated based on RECIST criteria. The toxicity grade was
      determined by NCI-CTC version 2. RESULTS: During January 2001 and April 2004, 17
      patients were entered in this study. The distribution of stage was IB2, 3; IIB,
      8; IIIB, 3; IVB, 1; recurrent, 2. There were 9 squamous cell carcinomas, 6
      adenocarcinomas, 1 adenosquamous cell carcinoma, and 1 small cell carcinoma. The
      overall response rate was 76% (2 CR, 11 PR, and 4 SD). No progression of disease
      was observed. All 5 adenocarcinoma patients in the neoadjuvant chemotherapy group
      responded including 1 pathological CR. The incidences of grade 3/4 toxicities
      were 76% for neutrocytopenia, 12% for thrombocytopenia, and 6% for anemia. No
      grade 3/4 neurotoxicity was observed. CONCLUSIONS: The combination of docetaxel
      and carboplatin is an effective and safe treatment for uterine cervix cancer.
      Further evaluation particularly targeted on cervical adenocarcinoma is warranted.

PMID- 15721430
TI  - Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6-12
      months after completion of primary chemotherapy, with exploratory TS, DPD, and TP
      correlates: a Gynecologic Oncology Group study.
AB  - PURPOSE: A phase II trial was conducted to evaluate the anti-tumor activity and
      adverse effects of capecitabine in women with measurable platinum-sensitive
      ovarian cancer or platinum-sensitive primary peritoneal cancer and to explore the
      ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and
      thymidine phosphorylase (TP) to predict response and toxicities. EXPERIMENTAL
      DESIGN: Patients were treated with a daily starting dose of 2500 mg/m2/day
      (divided in two doses given every 12 h) for 14 days of each 21-day cycle.
      Genotyping in the 5' and 3' ends of TS was performed in DNA from 23/23 pre
      treatment blood specimens. Relative gene expression of TS, DPD, and TP was
      quantified in 18/21 paraffin-embedded tumor specimens. RESULTS: Of the 27
      patients enrolled on study, 2 were never treated leaving 25 patients evaluable.
      Two patients (8.0%) achieved a partial response, 13 (52%) exhibited stable
      disease, 5 (20%) displayed increasing disease, and response could not be assessed
      in 5 (20%). The median time to progression and survival was 3.9 and 21.2 months,
      respectively. The most common serious toxicities were nausea/vomiting,
      gastrointestinal, and dermatological. There was one treatment-related death. TS
      expression was associated with severe nausea/vomiting (P = 0.039), but not with
      other severe toxicities. TS genotype or expression of DPD or TP was not
      associated with any of the severe toxicities. CONCLUSIONS: Based on the low
      response rate, this trial was closed after the first stage of accrual, the drug
      was not selected for further study in this patient population, and biomarker
      associations with response could not be assessed.

PMID- 15721431
TI  - Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as
      adjuvant treatment for uterine papillary serous carcinoma and clear cell
      carcinoma: a phase II Hoosier Oncology Group (HOG 97-01) study.
AB  - OBJECTIVE: A phase II study was conducted to evaluate the role of adjuvant
      intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy in
      patients with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma
      (CCC), after complete surgical staging. METHODS: Patients were required to have
      undergone complete surgical staging including maximal surgical resection.
      Residual < or =3 mm intraperitoneal disease, and pelvic and para-aortic lymph
      node dissection with negative nodes, were required. A dose of 15 mCi of
      intraperitoneal 32P was administered within 8 weeks of surgery. Vaginal
      brachytherapy was delivered using either high dose rate, total dose of 2100 cGy
      in 3 fractions (700 cGy per fraction prescribed to 0.5 cm depth from the vaginal
      surface) or low dose rate to 6500 cGy (prescribed to the vaginal surface) in 1-2
      fractions. RESULTS: For the 21 evaluable patients, distribution by FIGO stage was
      as follows: Stages I-IIB (17), Stages III-IV (4). The median follow-up was 39.6
      months (range: 5-63 months). No patients experienced grade 2-4 complications from
      their adjuvant therapy. Five patients suffered a recurrence: intraperitoneal [n =
      2], distal vaginal [n = 2], and one at the surgical scar. Following the 2 distal
      vagina recurrences early in the trial, the entire length of the vagina was
      treated with intracavitary brachytherapy. No additional vaginal recurrences were
      observed. The two-year overall survival, cause-specific survival, and disease
      free survival for the entire series were 89.2%, 89.2%, and 79.7%, respectively.
      CONCLUSIONS: Adjuvant therapy for UPSC and CCC with intraperitoneal 32P and
      vaginal brachytherapy after comprehensive surgical staging is feasible, well
      tolerated, and warrants further study on a larger scale.

PMID- 15721432
TI  - Rapid desensitization for hypersensitivity reactions to paclitaxel and docetaxel:
      a new standard protocol used in 77 successful treatments.
AB  - OBJECTIVE: Administration of paclitaxel is associated with hypersensitivity
      reactions (HSRs) in up to 9% of patients despite premedication. The purpose of
      this study was to evaluate the effectiveness of a standardized desensitization
      protocol in patients with HSRs to taxanes, based on our experience with
      carboplatin desensitization. METHODS: We analyzed seventeen consecutive patients
      with documented HSRs to taxanes who required continued treatment with a taxane
      agent. The patients were treated with either paclitaxel or docetaxel using the 6-
      to 7-h standard desensitization protocol. RESULTS: Seventeen patients who
      previously had severe taxane HSRs successfully completed 77 planned cycles of
      desensitization to paclitaxel or docetaxel, 72 of which were without reactions.
      Four patients developed HSRs during the desensitization protocol that were much
      less severe than their original HSRs and tolerated the re-administration of
      infusions without further reactions. Of these four patients, the first had palmar
      erythema 8 h after her 1st desensitization. The second patient had mild abdominal
      pain during her 1st cycle, and the third patient developed mild chest burning
      during her 2nd and 4th cycles. These three patients also completed subsequent
      desensitization cycles without reactions. The fourth patient developed a delayed
      urticaria reaction and gastrointestinal symptoms 6 h after completing her 1st
      desensitization. She elected to be treated with an alternative chemotherapy and
      did not receive additional courses of desensitization. CONCLUSION: The rapid
      standard desensitization protocol provides a safe and effective strategy for the
      re-administration of paclitaxel or docetaxel even after severe HSRs.

PMID- 15721433
TI  - HPV infections and cervical cancer prevention. Priorities and new directions.
      Highlights of EUROGIN 2004 International Expert Meeting, Nice, France, October 21
      23, 2004.

PMID- 15721434
TI  - Girls with Turner's syndrome with spontaneous menarche have an increased risk of
      endometrial carcinoma: a case report and review from the literature.
AB  - BACKGROUND: Patients with Turner's syndrome receiving unopposed estrogens for the
      induction of feminization have an increased risk of endometrial carcinoma. Only
      seven patients who were not treated with estrogen replacement therapy have been
      reported to have developed endometrial carcinoma at different age levels. CASE: A
      young girl with Turner's syndrome phenotype, spontaneous puberty, and karyotype
      45,X0/47,XXX from peripheral blood, after irregular menstrual cycles of 9 years,
      at the age of 21, was diagnosed with a non-invasive well-differentiated
      endometrial carcinoma confined to a hyperplastic endometrial polyp. Analysis of
      the ovarian tissue by FISH confirmed mosaicism: 45,X0/46,XX/47,XXX.
      CONCLUSION(S): The endogenous estrogen secretion from the ovaries might have
      caused malignancy in this case. Patients with Turner's syndrome with spontaneous
      menarche might carry a higher risk of endometrial carcinoma.

PMID- 15721435
TI  - Ovarian luteinized thecoma with sclerosing peritonitis in an adult woman treated
      with leuprolide and toremifene in complete remission at 5 years.
AB  - BACKGROUND: Luteinized thecoma of the ovary associated with sclerosing
      peritonitis is a rare pathologic condition without a standard strategy of
      treatment. CASE: We present the case of an ovarian luteinizing sclerosing thecoma
      in a 39-year-old woman. The patient underwent three laparotomic operations for
      subocclusive symptoms, revealing in both occasions the presence of sclerosing
      peritonitis, with large abdominal masses, including cysts containing clear fluid.
      Treatment with toremifene 20 mg/day and leuprolide resulted in a dramatic
      improvement of the performance status and complete remission of all the abdominal
      lesions. After 60 months follow-up, the patient is still disease-free.
      DISCUSSION: Antiestrogens plus LHRH agonists might be a noninvasive, effective
      and well-tolerated therapy for sclerosing peritonitis in patient operated for
      luteinized thecomas.

PMID- 15721436
TI  - A case report of rhabdomyosarcoma of the uterus associated with uterine
      inversion.
AB  - BACKGROUND: Alveolar rhabdomyosarcoma is an uncommon malignant soft tissue tumor
      rarely found in the genital tract. This tumor is associated with a poor
      prognosis, especially in the adult population. Equally as rare are non-puerperal
      uterine inversions secondary to sarcomas. CASE: A 21-year-old obese woman was
      initially evaluated with excessive vaginal bleeding. On exam, a large
      pedunculated mass protruding from the cervix was seen and biopsy of this mass
      revealed an alveolar rhabdomyosarcoma. The patient was treated with adjuvant
      chemotherapy consisting of VAC (Vincristine, Actinomycin, and Cyclophosphamide)
      for a presumed cervical rhabdomyosarcoma. After five cycles of chemotherapy the
      patient underwent a total abdominal hysterectomy and bilateral salpingo
      oophorectomy, at which time a complete uterine inversion was noted with the tumor
      located at the fundus of the uterus. Final pathology showed alveolar
      rhabdomyosarcoma of the uterus. The patient then received additional
      postoperative VAC regimen for a total of 10 treatments and remains in good health
      with no evidence of disease 20 months from diagnosis. CONCLUSION: This case
      report describes the only reported case of uterine inversion secondary to
      alveolar rhabdomyosarcoma of the uterus and discusses current therapeutic options
      for adults.

PMID- 15721437
TI  - Central pelvic recurrence 7 years after radical vaginal trachelectomy.
AB  - BACKGROUND: We report a case of central pelvic recurrence 7 years after radical
      vaginal trachelectomy for adenocarcinoma of the cervix. CASE: A 30-year-old woman
      was treated by radical vaginal trachelectomy and bilateral pelvic lymph node
      dissection (a fertility sparing procedure) in 1996 for cervical cancer. Pathology
      demonstrated a well differentiated, stage 1B1 adenocarcinoma. She presented 7
      years later with a central pelvic recurrence measuring 30 mm in width. She
      subsequently underwent radical hysterectomy for central clearance and did not
      require post-operative radiotherapy. CONCLUSIONS: Should selected patients who
      were initially treated by radical trachelectomy for early stage cervical cancer,
      in particular those with adenocarcinoma (as 50% of recurrences have been reported
      in this group of patients), be offered hysterectomy once child bearing is
      complete?

PMID- 15721438
TI  - Metastatic adenocarcinoma of the cervix in a delivery-induced traumatic lower
      vaginal tear.
AB  - BACKGROUND: Noncontiguous vaginal metastasis is rare in cervical cancer and is
      usually reported in the context of traumatic implantation. Traumatic vaginal
      implantation of cervical carcinoma has been documented in episiotomy, port site,
      or incision scars. CASE: We report the only case in the literature with vaginal
      metastasis associated with traumatic vaginal tear presenting with concomitant
      metastasis and the second case in the literature with a concomitant vaginal
      metastasis. Treatment consisted of organ-sparing chemoradiotherapy. Although the
      previous literature suggests that nonsurgical management of traumatic
      implantation metastases is associated with survivals of less than 1 year, there
      is no confirmed recurrent disease after 1 year of follow-up in our reported case.
      CONCLUSION: The feasibility and initial favorable outcome with chemoradiation is
      demonstrated in this rare presentation.

PMID- 15721439
TI  - Primary malignant mesothelioma of the peritoneum: a clinical and
      immunohistochemical study.
AB  - BACKGROUND: Primary peritoneal mesothelioma is regarded as a fatal disease that
      presents with progressive ascites at a relatively late stage of its natural
      history. Differential diagnosis between this rare tumor and both serous papillary
      carcinoma of the peritoneum and ovary can be problematic. CASE: A 54-year-old
      woman presented to our institution with a 4-month history of dull epigastric pain
      and increased abdominal girth. Exploratory laparotomy revealed the presence of
      extensive intraperitoneal dissemination of a malignant neoplasm without a
      recognizable primary site. Suboptimal cytoreduction was carried out, and
      histological diagnosis was that of a malignant epithelioid mesothelioma. This was
      confirmed with a panel of immunohistochemical markers. The patient despite having
      a complete response after adjuvant chemotherapy died 18 months after primary
      surgery. CONCLUSION: No single immunohistochemical stain is pathognomonic of
      peritoneal primary malignant mesothelioma (PMM), and the results of a panel of
      antibodies should be interpreted to set the diagnosis.

PMID- 15721440
TI  - Hormonal treatment of a recurrent granulosa cell tumor of the ovary: case report
      and review of the literature.
AB  - BACKGROUND: Granulosa cell tumors of the ovary are rare, primarily treated
      surgically. In advanced or recurrent disease, data are inconclusive regarding the
      benefit of either primary or adjuvant chemotherapy. Hormonal therapy has been
      suggested as an alternative treatment. CASE: Our patient had three recurrences of
      estrogen receptor negative and progesterone receptor positive GCT, the first two
      treated by surgery with or without adjuvant chemotherapy. For the third
      recurrence, the patient received alternating biweekly cycles of megestrol and
      tamoxifen. Computed tomography showed stable disease at 6 months, partial
      response at 18 months, and complete response at 22 months. The patient continues
      on hormonal therapy and has been disease-free for 5 years. CONCLUSION: This study
      and others suggest that hormonal therapy may provide another option for treating
      these relatively rare tumors.

PMID- 15721441
TI  - Leydig cell tumor in an elderly patient with complete androgen insensitivity
      syndrome.
AB  - BACKGROUND: Androgen insensitivity syndrome (AIS) is usually diagnosed in
      phenotypically female patients at puberty with primary amenorrhea. Testicular
      tumors often develop in patients with AIS, Sertoli cell tumor and seminoma being
      the most common types. Leydig cell tumor in AIS is extremely rare. CASE: A large
      abdominal tumor developed in a 73-year-old female patient. Physical examination
      and cytogenetic analysis revealed that the patient was with complete AIS. The
      patient underwent the extirpation of bilateral gonads including the tumor, pelvic
      lymph nodes, omentum and appendix vermiformis. The pathological diagnosis was
      malignant Leydig cell tumor of the left testis. There was no invasion or
      dissemination grossly and histologically. There was no adjuvant radiation or
      chemotherapy performed. The post-operative course was uneventful. The patient
      showed no evidence of disease at the post-operative 1 month checkup. CONCLUSION:
      We reported an extremely rare case of malignant Leydig cell tumor developing in
      an elderly AIS patient.

PMID- 15721442
TI  - Ectopic (pelvic) kidney mimicking bulky lymph nodes at pelvic lymphadenectomy.
AB  - BACKGROUND: Ectopic (pelvic) kidney is the most common congenital renal anomaly
      with an incidence of 1 in 500 to 1 in 2000. A pelvic kidney can be encountered at
      pelvic or paraaortic lymphadenectomy. CASE REPORTS: In two patients undergoing
      pelvic lymphadenectomy, lobulated tumors near the pelvic brim were initially
      interpreted as bulky lymph node conglomerates. Further dissection showed the
      ureter to originate from the masses, leading to a diagnosis of pelvic kidney.
      CONCLUSION: Pelvic kidneys mistaken for bulky lymph nodes are a potential
      intraoperative pitfall in patients with gynecologic malignancies. Keys to
      recognition include an index of suspicion, identifying the course of the ureter
      and origin of the renal vessels, and confirming absence of a kidney at the normal
      location.

PMID- 15721443
TI  - Primary squamous cell carcinoma of the endometrium: a case report with
      immunohistochemical and molecular study.
AB  - BACKGROUND: In this paper, we report a case of primary squamous cell carcinoma of
      the endometrium (PSCCE) with immunohistochemical and molecular study to evaluate
      the phenotype and to define the etiopathogenesis of this tumor. CASE HISTORY: A
      72-year-old woman was admitted to the Department of Obstetric and Gynecology for
      weight loss and pelvic mass. Abdominal ultrasonography disclosed the
      abdominopelvic mass with solid, cystic, and calcified areas. The patient
      underwent exploratory laparotomy. Intraoperative findings showed an enlarged
      uterus with perforation of its wall. The surface of omentum was covered with
      small white nodules. Pathological examination showed features of PSCCE.
      Immunohistochemical analysis with antibodies for estrogen and progesterone
      receptors disclosed negativity of neoplastic elements. Immunostaining with p53
      tumor-suppressor protein showed the mutation of p53 tumor-suppressor protein as a
      strong nuclear positivity. Molecular study by polymerase chain reaction (PCR)
      amplification of tumor DNA did not show any signal for human papilloma virus
      (HPV) DNA. CONCLUSION: In summary, unlike the example reported in the literature
      by others, in the present case we demonstrated that PSCCE is not due to HPV
      infection, but probably to other pathogenetic mechanisms, which cause a mutation
      of p53 tumor-suppressor gene. Thus, it is reasonable to conclude that both HPV
      infection and unclear carcinogenic factors, responsible of p53 tumor-suppressor
      gene mutation, may cause PSCCE.

PMID- 15721444
TI  - Solitary fibrous tumor arising in the fallopian tube.
AB  - BACKGROUND: Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually
      arises in the pleura. Although this tumor has been described at other sites, in
      the female genital tract it is extremely uncommon. CASE: We present a case of
      solitary fibrous tumor arising in the fallopian tube. A 32-year-old woman who
      presented with acute flank pain had a presumptive diagnosis of leiomyoma of the
      fallopian tube after abdominopelvic ultrasound. The adnexal mass was excised
      laparoscopically. Histologic examination showed the characteristic features of a
      solitary fibrous tumor. CONCLUSION: Although rare, the diagnosis of solitary
      fibrous tumor can be considered in the differential diagnosis of adnexal masses.

PMID- 15721445
TI  - Prolonged survival following salvage surgery for chemorefractory ovarian immature
      teratoma: a case report and review of the literature.
AB  - BACKGROUND: Data regarding salvage surgery for ovarian immature teratoma (IT) are
      lacking despite its established role in the management of chemorefractory
      testicular germ cell tumors. In this report, a case of advanced IT that was
      salvaged by secondary cytoreduction following failure of both primary therapy and
      salvage chemotherapy is described, and the available literature is reviewed.
      CASE: A 28-year-old patient underwent primary cytoreductive surgery followed by
      platinum-based chemotherapy for stage IIIC, grade 3, ovarian IT. Second-line
      chemotherapy was administered after residual disease was identified at second
      look surgery. Following failure of salvage chemotherapy, aggressive secondary
      debulking resulted in long-term disease-free survival of over 48 months.
      CONCLUSION: There appears to be a distinct role for salvage surgery in selected
      cases of chemorefractory IT. More studies are needed to further define the subset
      of patients who benefit most from this management approach.

PMID- 15721446
TI  - Combined positron emission tomography and computed tomography for the detection
      of recurrent ovarian mucinous adenocarcinoma.
AB  - BACKGROUND: The role of combined positron emission tomography and computed
      tomography (PET-CT) in the diagnosis of recurrent ovarian mucinous adenocarcinoma
      is uncertain because of previous reports that PET has limited sensitivity in the
      detection of mucinous neoplasms. CASE: A 71-year-old white woman presented with
      complaints of right lower quadrant pain and a palpable adnexal mass. Physical
      examination and transvaginal ultrasonography revealed a 12 x 13 cm cystic mass in
      the left side of the pelvis. Exploratory laparotomy, optimal tumor-reductive
      surgery, total abdominal hysterectomy, bilateral salpingo-oophorectomy,
      appendectomy, and omentectomy were performed. The diagnosis was FIGO stage IIIC
      well-differentiated ovarian mucinous adenocarcinoma. The patient was treated with
      6 cycles of carboplatin and paclitaxel. Four months after completing
      chemotherapy, the patient was noted to have an elevated serum CA125 level (72
      U/mL), being otherwise asymptomatic. Findings on abdominal and pelvic CT were
      compatible with postsurgical changes. PET-CT was performed and revealed increased
      metabolism along the posterior aspect of the right rectus abdominis muscle and
      abutting the anterior wall of an adjacent loop of bowel. CONCLUSION: PET-CT may
      identify clinically occult recurrent ovarian mucinous adenocarcinoma.

PMID- 15721447
TI  - Extrarenal Wilms' tumor of the uterine corpus.
AB  - BACKGROUND: Extrarenal Wilms' tumors (EWT) are rare. In the female genital tract,
      only 15 cases (6 adults, 9 children) of EWT have been reported. A case of uterine
      Wilms' tumor in an adult is presented with a review of the literature. CASE: A 44
      year-old woman presented with a bleeding polypoid cervical mass. Biopsy revealed
      EWT. She was surgically staged, received chemotherapy, and is without evidence of
      disease at 1 year follow-up. CONCLUSIONS: Prognosis and treatment of EWT may
      differ by location and patient age. Literature review of uterine Wilms' tumor
      reveals favorable outcome with (1) focal disease confined to the uterus and (2)
      adequate surgery, including hysterectomy. The National Wilms' Tumor Study Group
      recommends adjuvant chemotherapy for all EWT. Radiation may be reserved for
      patients with residual, metastatic and/or recurrent disease.

PMID- 15721448
TI  - Plasmacytoid dendritic cells are present in cervical carcinoma and become
      activated by human papillomavirus type 16 virus-like particles.
AB  - OBJECTIVES: Plasmacytoid dendritic cells (PDC) play an important role in the
      innate immune response to viral infections through the secretion of high levels
      of IFNalpha. We investigated whether PDC play a role in Human Papillomavirus
      (HPV) associated cervical carcinoma. METHODS: Frozen sections of 18 cervical
      carcinomas were analyzed for the presence of myeloid and plasmacytoid DC. To
      study whether the HPV virus can activate PDC, expression of putative VLP
      receptors (CD49f and CD16) was analyzed on PDC in peripheral blood mononuclear
      cells of healthy donors. Furthermore, CD83 induction and IFNalpha production by
      purified blood-derived PDC was measured after incubation with HPV 16 virus like
      particles (VLP). RESULTS: PDC were detected in 83% of the CxCa cases, primarily
      in the stroma. PDC express one of the putative VLP receptors (CD49f). IFNalpha
      production but no CD83 expression was induced in PDC upon incubation with VLP.
      CONCLUSION: Our data suggest that PDC, which are at hand locally in the cervix,
      play a role in the natural immune response against HPV and identify PDC as
      possible targets for VLP-based vaccines.

PMID- 15721449
TI  - Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian
      cancer.
AB  - BACKGROUND: Angiogenesis is pivotal in the development and progression of ovarian
      cancer and is an ideal candidate for novel treatment approaches. CASE: A case of
      advanced, recurrent and refractory serous carcinoma is presented that responded
      to bevacizumab 15 mg/m2 intravenously every 3 weeks after failing eleventh line
      cytotoxic chemotherapy and radiation. An objective durable response lasting at
      least 5 months was documented. CONCLUSION: Bevacizumab has activity in epithelial
      ovarian carcinoma and larger scale trials are indicated.

PMID- 15721450
TI  - Re: "clinical implications of a rising serum CA-125 within the normal range in
      patients with epithelial ovarian cancer: a preliminary investigation".

PMID- 15721451
TI  - Increasing somatostatin analogues until effective.

PMID- 15721453
TI  - Losing tolerance with zero tolerance.

PMID- 15721454
TI  - Chlamydia--a testing issue.

PMID- 15721455
TI  - Vaccine development for chronic myelogenous leukaemia.

PMID- 15721456
TI  - Head cooling in neonatal hypoxic-ischaemic encephalopathy.

PMID- 15721457
TI  - Gene-expression profiling in breast cancer.

PMID- 15721458
TI  - Smoke, mirrors, and Gulf War illness.

PMID- 15721459
TI  - What is the clinical impact of occult hepatitis B virus infection?

PMID- 15721460
TI  - New-onset diabetes after transplantation: a threat to graft and patient survival.

PMID- 15721461
TI  - Resuscitation of newborn infants.

PMID- 15721462
TI  - WHO and biological weapons investigations.

PMID- 15721466
TI  - Reports of bioethics' demise are premature.

PMID- 15721465
TI  - Malaria misconceptions.

PMID- 15721468
TI  - HIV-infected women in ART programmes.

PMID- 15721469
TI  - The long and creative arm of the drug industry.

PMID- 15721470
TI  - Effect of a p210 multipeptide vaccine associated with imatinib or interferon in
      patients with chronic myeloid leukaemia and persistent residual disease: a
      multicentre observational trial.
AB  - BACKGROUND: Although imatinib is the standard treatment for chronic myeloid
      leukaemia, not all patients reach complete cytogenetic remission (CCR) and most
      maintain detectable disease at the molecular level. We investigated whether a
      vaccine targeting the BCR-ABL-derived p210 fusion protein was an active and
      specific immunotherapy. METHODS: We recruited 16 patients who had chronic myeloid
      leukaemia (with the b3a2 fusion point of p210), stable residual disease, a
      minimum treatment of 12 months of imatinib or 24 months of interferon alfa, and
      no further reduction of residual disease for at least 6 months preceding
      enrollment. They were given six vaccinations with a peptide vaccine derived from
      the sequence p210-b3a2 plus molgramostim and QS-21 as adjuvants (CMLVAX100)
      before assessment of immunological and disease response, which included detecting
      amounts of b3a2 transcripts by standardised quantitative real-time reverse
      transcriptase PCR. RESULTS: Of ten patients on imatinib, nine started CMLVAX100
      having had a median of 10 months' stable cytogenetic disease (median 10%
      Philadelphia-chromosome-positive metaphases), whereas one started in stable CCR.
      All patients' cytogenetic responses improved after six vaccinations, with five
      reaching CCR. Notably, three of these five patients also had undetectable amounts
      of b3a2 transcript (BCR-ABL:beta2 microglobulin ratio <0.00001). Six patients on
      interferon alfa treatment with a median of 17 months' stable residual disease
      (median 13% Philadelphia-chromosome-positive cells) were also vaccinated. All but
      one had improved cytogenetic responses, and two reached CCR. Overall, we recorded
      peptide-specific delayed-type hypersensitivity (in 11 of 16 patients), CD4 cell
      proliferation (13 of 14 assessed), and interferon gamma production (five of five
      assessed). INTERPRETATION: Addition of CMLVAX100 to conventional treatment in
      patients with chronic myeloid leukaemia might favour further reduction of
      residual disease and increase the number of patients reaching a molecular
      response.

PMID- 15721471
TI  - Selective head cooling with mild systemic hypothermia after neonatal
      encephalopathy: multicentre randomised trial.
AB  - BACKGROUND: Cerebral hypothermia can improve outcome of experimental perinatal
      hypoxia-ischaemia. We did a multicentre randomised controlled trial to find out
      if delayed head cooling can improve neurodevelopmental outcome in babies with
      neonatal encephalopathy. METHODS: 234 term infants with moderate to severe
      neonatal encephalopathy and abnormal amplitude integrated electroencephalography
      (aEEG) were randomly assigned to either head cooling for 72 h, within 6 h of
      birth, with rectal temperature maintained at 34-35 degrees C (n=116), or
      conventional care (n=118). Primary outcome was death or severe disability at 18
      months. Analysis was by intention to treat. We examined in two predefined
      subgroup analyses the effect of hypothermia in babies with the most severe aEEG
      changes before randomisation--ie, severe loss of background amplitude, and
      seizures--and those with less severe changes. FINDINGS: In 16 babies, follow-up
      data were not available. Thus in 218 infants (93%), 73/110 (66%) allocated
      conventional care and 59/108 (55%) assigned head cooling died or had severe
      disability at 18 months (odds ratio 0.61; 95% CI 0.34-1.09, p=0.1). After
      adjustment for the severity of aEEG changes with a logistic regression model, the
      odds ratio for hypothermia treatment was 0.57 (0.32-1.01, p=0.05). No difference
      was noted in the frequency of clinically important complications. Predefined
      subgroup analysis suggested that head cooling had no effect in infants with the
      most severe aEEG changes (n=46, 1.8; 0.49-6.4, p=0.51), but was beneficial in
      infants with less severe aEEG changes (n=172, 0.42; 0.22-0.80, p=0.009).
      INTERPRETATION: These data suggest that although induced head cooling is not
      protective in a mixed population of infants with neonatal encephalopathy, it
      could safely improve survival without severe neurodevelopmental disability in
      infants with less severe aEEG changes.

PMID- 15721472
TI  - Gene-expression profiles to predict distant metastasis of lymph-node-negative
      primary breast cancer.
AB  - BACKGROUND: Genome-wide measures of gene expression can identify patterns of gene
      activity that subclassify tumours and might provide a better means than is
      currently available for individual risk assessment in patients with lymph-node
      negative breast cancer. METHODS: We analysed, with Affymetrix Human U133a
      GeneChips, the expression of 22000 transcripts from total RNA of frozen tumour
      samples from 286 lymph-node-negative patients who had not received adjuvant
      systemic treatment. FINDINGS: In a training set of 115 tumours, we identified a
      76-gene signature consisting of 60 genes for patients positive for oestrogen
      receptors (ER) and 16 genes for ER-negative patients. This signature showed 93%
      sensitivity and 48% specificity in a subsequent independent testing set of 171
      lymph-node-negative patients. The gene profile was highly informative in
      identifying patients who developed distant metastases within 5 years (hazard
      ratio 5.67 [95% CI 2.59-12.4]), even when corrected for traditional prognostic
      factors in multivariate analysis (5.55 [2.46-12.5]). The 76-gene profile also
      represented a strong prognostic factor for the development of metastasis in the
      subgroups of 84 premenopausal patients (9.60 [2.28-40.5]), 87 postmenopausal
      patients (4.04 [1.57-10.4]), and 79 patients with tumours of 10-20 mm (14.1 [3.34
      59.2]), a group of patients for whom prediction of prognosis is especially
      difficult. INTERPRETATION: The identified signature provides a powerful tool for
      identification of patients at high risk of distant recurrence. The ability to
      identify patients who have a favourable prognosis could, after independent
      confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose
      less aggressive therapeutic options.

PMID- 15721473
TI  - Unlucky...unlucky...

PMID- 15721474
TI  - Long-term survival after colorectal surgery associated with buffy-coat-poor and
      leucocyte-depleted blood transfusion: a follow-up study.
AB  - A Danish clinical trial showed that transfusion with leucocyte-depleted red blood
      cells reduces postoperative infectious complications compared with cells without
      buffy-coat. However, the effect on long-term outcome is unknown. We followed up
      the 142 cancer patients transfused with buffy-coat-poor red cells, the 118
      transfused with leucocyte-depleted blood, and the 329 who were not transfused,
      until 2003. After 7 years' follow-up, survival for those with leucocyte-depleted
      blood transfusion (46 [41%]) was not significantly different from transfusion of
      blood without buffy-coat (59 [45%], p=0.51). Although survival is reduced by
      blood transfusion, it does not differ between the two transfusion regimens.

PMID- 15721475
TI  - Blockade of HERG channels by HIV protease inhibitors.
AB  - The HIV protease inhibitor class of antiretroviral drug causes unpredicted
      adverse effects by changing elements of normal cellular metabolism. A case of QT
      prolongation in a patient receiving protease inhibitors made us question whether
      these drugs might be responsible. We identified 24 patients with QT prolongation
      or torsade de pointes, or both, associated with protease inhibitors, using the
      Food and Drug Administration's voluntary adverse event reporting system.
      Attending physicians thought that protease inhibitors were the most probable
      cause of these symptoms in 14 of the patients. Drug-induced QT prolongation is
      usually caused by block of human ether-a-go-go-related gene (HERG) potassium
      channels, and we showed that lopinavir, nelfinavir, ritonavir, and saquinavir
      caused dose-dependent block of HERG channels heterologously expressed in HEK293
      cells in vitro. We also recorded block by lopinavir of repolarising potassium
      current (I(Kr)) channels in neonatal mouse cardiac myocytes. Our data show that
      four protease inhibitors block HERG channels, suggesting that protease inhibitors
      could predispose individuals to QT prolongation and torsade de pointes.

PMID- 15721476
TI  - Cutaneous melanoma.
AB  - Episodic exposure of fair-skinned individuals to intense sunlight is thought to
      be responsible for the steadily increasing melanoma incidence worldwide over
      recent decades. Rarely, melanoma susceptibility is increased more than tenfold by
      heritable mutations in the cell cycle regulatory genes CDKN2A and CDK4. Effective
      treatment requires early diagnosis followed by surgical excision with adequately
      wide margins. Sentinel lymph node biopsy provides accurate staging, but no
      published results are yet available from clinical trials designed to assess the
      therapeutic efficacy of early complete regional node dissection in those with
      metastatic disease in a sentinel node. Magnetic resonance spectroscopy is one
      technique under investigation for non-invasive, in-situ assessment of sentinel
      nodes. Localised metastatic disease is best treated surgically. No postoperative
      adjuvant therapy is of proven value for improving overall survival, although
      numerous clinical trials of vaccines and cytokines are in progress. Medical
      therapies have contributed little to the control of established metastatic
      disease, but molecular pathways recently identified as being central to melanoma
      growth and apoptosis are under intense investigation for their potential as
      therapeutic targets.

PMID- 15721477
TI  - The influence of violent media on children and adolescents:a public-health
      approach.
AB  - There is continuing debate on the extent of the effects of media violence on
      children and young people, and how to investigate these effects. The aim of this
      review is to consider the research evidence from a public-health perspective. A
      search of published work revealed five meta-analytic reviews and one quasi
      systematic review, all of which were from North America. There is consistent
      evidence that violent imagery in television, film and video, and computer games
      has substantial short-term effects on arousal, thoughts, and emotions, increasing
      the likelihood of aggressive or fearful behaviour in younger children, especially
      in boys. The evidence becomes inconsistent when considering older children and
      teenagers, and long-term outcomes for all ages. The multifactorial nature of
      aggression is emphasised, together with the methodological difficulties of
      showing causation. Nevertheless, a small but significant association is shown in
      the research, with an effect size that has a substantial effect on public health.
      By contrast, only weak evidence from correlation studies links media violence
      directly to crime.

PMID- 15721479
TI  - The Millennium Project: the positive health implications of improved
      environmental sustainability.

PMID- 15721478
TI  - A proposed charter for clinical trial data monitoring committees: helping them to
      do their job well.
AB  - Formal monitoring of data from randomised controlled trials (RCTs) is becoming
      more common. Wide variation exists in the structure and organisation of data
      monitoring committees (DMCs), with little guidance on how they should operate. We
      used various strategies to consider the behavioural, procedural, and
      organisational aspects of data monitoring in RCTs: systematic reviews of DMCs and
      small group processes in decision making; surveys of reports of RCTs, recently
      completed and ongoing RCTs, and the policies of major organisations connected
      with RCTs; detailed case studies of four DMCs that faced difficult decisions; and
      interviews with experienced DMC members. The findings aided the development of a
      template for a charter for DMCs. We summarise the findings and outline the key
      considerations at every stage of the data monitoring process. Widespread use of a
      charter for the structure and organisation of DMCs would promote a systematic and
      transparent approach, and enable them to operate more effectively and
      efficiently.

PMID- 15721480
TI  - Skin ulcers in a returned traveller.

PMID- 15721481
TI  - Effects of angiotensin II type 1 receptor blockade on the oxidative stress in
      spontaneously hypertensive rat tissues.
AB  - The aim of this work was to investigate the production of oxidative damage in
      homogenized kidney, liver and brain of spontaneously hypertensive rats (SHR), as
      well as the involvement of angiotensin (Ang) II in this process. Groups of 12
      week-old SHR and Wistar Kyoto rats (WKY) were given 10 mg/kg/day losartan in the
      drinking water during 14 days. Other groups of WKY and SHR without treatment were
      used as controls. The production of thiobarbituric acid reactive substances
      (TBARS), reduced glutathione (GSH) and the activity of the antioxidant enzymes
      catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were
      determined. No significant difference in TBARS was observed between untreated SHR
      or WKY rats; GSH content was lower in the liver but higher in the brain of SHR
      compared to WKY rats. In tissues from the SHR group, SOD and Gpx activities were
      reduced, whereas CAT activity was slightly increased in kidney. TBARS levels did
      not change in WKY rats after losartan administration, but were reduced in SHR
      liver and brain. Losartan treatment decreased GSH content in WKY kidney, but
      increased GSH in SHR liver. The activity of the antioxidant enzymes was not
      modified by losartan in WKY rats; however, their activities increased in tissues
      from treated SHR. The lower activity of antioxidant enzymes in tissues from
      hypertensive rats compared to those detected in normotensive controls, indicates
      oxidative stress production. Ang II seems to play no role in this process in
      normotensive animals, although AT1 receptor blockade in SHR enhances the
      enzymatic activity indicating that Ang II is implicated in oxidative stress
      generation in the hypertensive animals.

PMID- 15721482
TI  - Chronic administration of adrenomedullin attenuates the hypertension and
      increases renal nitric oxide synthase in Dahl salt-sensitive rats.
AB  - Adrenomedullin reduces systemic blood pressure and increases urinary sodium
      excretion partly through the release of nitric oxide. We hypothesized that
      chronic adrenomedullin infusion ameliorates salt-sensitive hypertension and
      increases the expression of renal nitric oxide synthase (NOS) in Dahl salt
      sensitive (DS) rats, because the reduced renal NOS expression promotes salt
      sensitivity. DS rats and Dahl salt-resistant (DR) rats were fed a high sodium
      diet (8.0% NaCl) for 3 weeks. The high sodium diet resulted in an increase in
      blood pressure and a reduction of urinary sodium excretion in association with
      increased renal adrenomedullin concentrations and decreased expression of renal
      neuronal NOS (nNOS) and renal medullary endothelial NOS (eNOS) in DS rats
      compared with DR rats. Chronic adrenomedullin infusion partly inhibited the
      increase of blood pressure and proteinuria in association with a restoration of
      renal nNOS and medullary eNOS expression in DS rats under the high sodium diet.
      The immunohistochemical analysis revealed that the restored renal nNOS expression
      induced by chronic adrenomedullin infusion may reflect the restoration of nNOS
      expression in the macula densa and inner medullary collecting duct. These results
      suggest that adrenomedullin infusion has beneficial effects on this hypertension
      probably in part through restored renal NOS expression in DS rats.

PMID- 15721483
TI  - Hemodynamic effects of python neuropeptide gamma in the anesthetized python,
      Python regius.
AB  - The effects of python neuropeptide gamma (NPgamma) on hemodynamic parameters have
      been investigated in the anesthetized ball python (Python regius). Bolus intra
      arterial injections of synthetic python NPgamma (1-300 pmol kg-1) produced a dose
      dependent decrease in systemic arterial blood pressure (Psys) concomitant with
      increases in systemic vascular conductance (Gsys), total cardiac output and
      stroke volume, but only minor effects on heart rate. The peptide had no
      significant effect on pulmonary arterial blood pressure (Ppul) and caused only a
      small increase in pulmonary conductance (Gpul) at the highest dose. In the
      systemic circulation, the potency of the NK1 receptor-selective agonist
      [Sar9,Met(0(2))11] substance P was >100-fold greater than the NK2 receptor
      selective agonist [betaAla8] neurokinin A-(4-10)-peptide suggesting that the
      python cardiovascular system is associated with a receptor that resembles the
      mammalian NK1 receptor more closely than the NK2 receptor. Administration of the
      inhibitor of nitric oxide synthesis, L-nitro-arginine-methylester (L-NAME; 150 mg
      kg-1), resulted in a significant (P<0.05) increase in Psys as well as a decrease
      in Gsys, but no effect on Ppul and Gpul. Conversely, the nitric oxide donor,
      sodium nitroprusside (SNP; 60 microg kg-1) produced a significant (P<0.05)
      decrease in Psys along with an increase in Gsys and pulmonary blood flow.
      However, neither L-NAME nor indomethacin (10 mg kg-1) reduced the cardiovascular
      responses to NPgamma. Thus, nitric oxide is involved in regulation of basal
      vascular tone in the python, but neither nitric oxide nor prostaglandins mediate
      the vasodilatory action of NPgamma.

PMID- 15721484
TI  - Expression of somatostatin receptor mRNAs is regulated in vivo by growth hormone,
      insulin, and insulin-like growth factor-I in rainbow trout (Oncorhynchus mykiss).
AB  - Somatostatins are a diverse family of peptide hormones that regulate various
      aspects of growth, development, and metabolism through interactions with numerous
      somatostatin receptor subtypes (SSTRs) on target tissues. In this study, we used
      rainbow trout to evaluate the effects of growth hormone (GH), insulin (INS), and
      insulin-like growth factor-I (IGF-I) on the expression of SSTR 1A, 1B and 2
      mRNAs. GH regulated the expression of SSTRs in a subtype- and tissue-specific
      manner. GH reduced SSTR 1A, 1B, and 2 expression in optic tectum, reduced SSTR 1A
      and 1B expression in pancreas, reduced SSTR 1A expression in liver, and increased
      hepatic SSTR 1B expression. INS also regulated SSTR expression in a subtype- and
      tissue-specific manner. INS reduced SSTR 1B expression in optic tectum, increased
      SSTR 2 expression in pancreas, and increased SSTR 1B and 2 expression in liver.
      IGF-I generally decreased the expression of all SSTRs. These data indicate that
      GH, INS, and IGF-I modulate the expression of SSTRs and suggest that independent
      mechanisms may serve to regulate the various receptor subtypes.

PMID- 15721486
TI  - Role of Ras/PKCzeta/MEK/ERK1/2 signaling pathway in angiotensin II-induced
      vascular smooth muscle cell proliferation.
AB  - The role of protein kinase C (PKC) and its cross talk with extracellular signal
      regulated kinase (ERK) cascade in angiotensin II (AngII)-elicited vascular smooth
      muscle cell (VSMC) proliferation are still unclear. In this study, the PKC
      pathway of AngII to activate ERK1/2 and induce cell proliferation was
      investigated in rat aortic smooth muscle cells. The proliferation of VSMCs was
      tested by [3H]-thymidine incorporation assay. Phosphorylated and non
      phosphorylated PKCzeta, ERK1/2, Elk-1, and mitogen-activated ERK-activating
      kinase (MEK) were estimated by Western blot analysis. The interactions of signal
      molecules were examined by immunoprecipitation. AngII-induced VSMC proliferation
      and activation of ERK1/2 and nuclear transcription factor Elk-1 were all down
      regulated by PKC non-specific inhibitor (staurosporine) and PKCzeta
      pseudosubstrate inhibitor (PS-PKCzeta). Dominant negative Ras transfection into
      VSMCs decreased AngII-induced PKCzeta and ERK1/2 phosphorylation. AngII
      stimulated the association of PKCzeta with Ras. AngII-induced MEK phosphorylation
      was inhibited by PKCzeta pseudosubstrate inhibitor and the PKCzeta-MEK complex
      was detected by immunoprecipitation. These results suggest that PKCzeta isoform
      is involved in VSMC proliferation and Elk-1 activation. AngII can activate ERK1/2
      by Ras/PKCzeta/MEK pathway, which may be one of the important signal transduction
      pathways in AngII-induced VSMC proliferation.

PMID- 15721487
TI  - Ghrelin activates neuronal constitutive nitric oxide synthase in pancreatic islet
      cells while inhibiting insulin release and stimulating glucagon release.
AB  - In view of our previous data, showing that ghrelin and nitric oxide (NO) display
      apparently parallel effects on insulin secretion (inhibitory) and glucagon
      secretion (stimulatory), we have now investigated the effect of ghrelin on islet
      hormone secretion in relation to its effect on NO synthase (NOS) isoenzymes in
      isolated rat pancreatic islets. Dose-response studies revealed that ghrelin at
      concentrations of 0.01-1 micromol l-1 inhibited insulin secretion stimulated by
      8.3 mmol l-1 glucose, while ghrelin at concentrations lower than the
      physiological range (0.01 pmol l-1 to 1 nmol l-1) were without effect. In
      contrast, glucagon secretion was stimulated by 1.0 nmol l-1 to 1 micromol l-1
      ghrelin. These effects of ghrelin on insulin and glucagon secretion were
      accompanied by increased NO production through activation of neuronal
      constitutive NOS (ncNOS). Ghrelin had no appreciable effect on the activity of
      inducible NOS (iNOS) in the islets. Addition of an NO scavenger (cPTIO) or the
      NOS inhibitor L-NAME to the incubation medium prevented the effects of ghrelin on
      hormone secretion from isolated islets. The present results confirm our previous
      data showing that ghrelin inhibits insulin and stimulates glucagon secretion from
      pancreatic islets of the mouse and we now show similar effects in rat islets. The
      effects of ghrelin were accompanied by an increased rate of NO production.
      Conceivably, ncNOS activation partly accounts for to the inhibitory effect of
      ghrelin on insulin secretion and the stimulatory effect of ghrelin on glucagon
      secretion.

PMID- 15721485
TI  - Behavioral effects of local microinfusion of pituitary adenylate cyclase
      activating polypeptide (PACAP) into the paraventricular nucleus of the
      hypothalamus (PVN).
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has been implicated in
      the regulation of several autonomic and neuroendocrine functions. In the
      hypothalamic paraventricular nucleus (PVN), for example, PACAP-immunoreactive
      fibers densely innervate corticotropin-releasing hormone (CRH)-containing neurons
      in the medial parvocellular region, suggesting that PACAP acts to mediate stress
      responses. Therefore, we examined the behavioral effects of an intra-PVN PACAP
      injection (25 pmol) in combination with a mild stressor. PACAP or artificial
      cerebrospinal fluid (aCSF) was microinjected into the PVN (0.25 l) and then
      animals were restrained or placed in their home cage for 5 min. Exploratory
      activity (total distance traveled) and scored behaviors (face washing, body
      grooming, wet dog shakes, and rearing) were observed in a familiar open field for
      10 min. In animals receiving aCSF, there were no behavioral differences between
      restrained and unrestrained groups. For the entire 10-min observation period,
      animals receiving PACAP, whether restrained or not, displayed elevated face
      washing and body grooming with decreased locomotor activity and rearing. Among
      PACAP-injected animals, restrained animals displayed increased body grooming
      compared to unrestrained animals during the first 2 min in the open field
      suggesting a summation of the effects of peptide injection and stressor. The
      observed elevation in grooming is consistent with previous studies reporting
      similar increases following electrical-, NMDA-, CRH-, or stressor-induced
      activation of the PVN. Thus, at the level of the PVN, PACAP may act as an
      excitatory neuropeptide and augment behavioral responses to stressors.

PMID- 15721488
TI  - Investigation of the mechanisms involved in the central effects of glucagon-like
      peptide-1 on ethanol-induced gastric mucosal lesions.
AB  - The aim of this study was to investigate the effects of intracerebroventricularly
      injected glucagon-like peptide-1 (GLP-1) on ethanol-induced gastric mucosal
      damage and to elucidate the mechanisms involved. Absolute ethanol was
      administered through an orogastric cannula 5 min before GLP-1 (1 microg/10
      microl) injection. One hour later, the rats were decapitated, their stomachs were
      removed and scored for mucosal damage. GLP-1 inhibited the ethanol-induced
      gastric mucosal damage by 92%. Centrally injected atropine sulphate, a muscarinic
      receptor antagonist (5 microg/10 microl), prevented the gastroprotective effect
      of GLP-1, while mecamylamine, a nicotinic receptor antagonist (25 microg/10
      microl), was ineffective. Peripherally injected atropine methyl nitrate (1 mg/kg)
      did not change the effect of GLP-1, but mecamylamine (5 mg/kg) blocked it.
      Cysteamine, a somatostatin depletor (280 mg/kg, s.c.), did not affect the
      protective activity of GLP-1, while inhibition of nitric oxide (NO) synthesis by
      L-NAME (3 mg/kg, i.v.) significantly abolished the protective effect of GLP-1 on
      ethanol-induced gastric mucosal lesions. We conclude that central muscarinic and
      peripheral nicotinic cholinergic receptors and NO, but not somatostatin,
      contribute to the protective effect of intracerebroventricularly injected GLP-1
      on ethanol-induced gastric mucosal damage.

PMID- 15721489
TI  - Leptin concentrations in the abdominal subcutaneous adipose tissue of patients
      with anorexia nervosa assessed by in vivo microdialysis.
AB  - OBJECTIVE: The adipocyte-derived hormone leptin is involved in energy metabolism
      and body weight regulation. Plasma leptin concentrations are significantly
      reduced in patients with anorexia nervosa (AN) and with severe malnutrition.
      Whether reduced plasma leptin is reflected by its decreased production by the
      adipose tissue is unknown. METHODS: In the present study we measured leptin
      concentrations locally in the abdominal subcutaneous adipose tissue of 9 female
      AN patients and 11 healthy controls by in vivo microdialysis. RESULTS: Adipose
      tissue free leptin levels were not different in patients with AN compared to
      controls (2.59+/-1.99 vs 2.36+/-0.25 ng/ml, P>0.05). Plasma leptin soluble
      receptor (sOb-R) levels were significantly higher in patients with AN than in
      healthy subjects (58.05+/-38.69 vs 12.79+/-5.08 U/ml, P<0.01). The area of
      adipocyte in AN was considerably smaller than in the controls (183+/-104.01
      microm2 compared to 2145.8+/-1003.41). CONCLUSIONS: We conclude that decreased
      plasma leptin levels in patients with AN are not directly related to dialysate
      leptin levels in the abdominal subcutaneous adipose tissue.

PMID- 15721490
TI  - Role of pituitary adenylate cyclase-activating peptide (PACAP) in the cyclic
      recruitment of immature follicles in the rat ovary.
AB  - Following the midcyclic gonadotropin surge, PACAP is transiently expressed for
      approximately 12 h in the cyclic adult rat ovary. PACAP is observed in
      granulosa/lutein cells of the large mature follicles destined to ovulate and is
      believed to be a regulator of acute progesterone production and luteinization in
      these follicles. PACAP is also observed in solitary theca cells of immature
      follicles and in interstitial glandular cells intimately surrounding immature
      follicles. To examine if PACAP could be involved in the process of cyclic
      recruitment of such immature follicles, we primed immature granulosa cells from
      prepubertal ovaries with PACAP (1 nM and 100 nM) for 12 h. The treatment
      significantly stimulated the subsequent 24 h FSH-induced estradiol production
      (2.2 and 2.4 fold, respectively). The response seemed to be caused by a
      stimulation of aromatase activity. Estradiol production induced by testosterone
      was increased 2.4 and 2.6 fold, respectively, whereas functional FSH-receptors
      (cAMP production following FSH stimulation) or spontaneous apoptosis
      (immunohistochemical detection of DNA fragments) was unaffected. We conclude that
      PACAP priming of immature rat granulosa cells for 12 h increases subsequent FSH
      induced estradiol production and that PACAP could be involved in the cyclic
      recruitment of immature follicles in the adult rat ovary.

PMID- 15721491
TI  - The structural organization of aurein precursor cDNAs from the skin secretion of
      the Australian green and golden bell frog, Litoria aurea.
AB  - Aureins are a family of peptides (13-25 residues), some of which possess potent
      antimicrobial and anti-cancer properties, which have been classified into 5
      subgroups based upon primary structural similarities. They were originally
      isolated from the defensive skin secretions of the closely related Australian
      bell frogs, Litoria aurea and Litoria raniformis, and of the 23 aurein peptides
      identified, 10 are common to both species. Using a recently developed technique,
      we have constructed a cDNA library from the defensive secretion of the green and
      golden bell frog, L. aurea, and successfully cloned a range of aurein precursor
      transcripts containing entire open-reading frames. All open-reading frames
      consisted of a putative signal peptide and an acidic pro-region followed by a
      single copy of aurein. The deduced precursor structures for the most active
      aureins (2.2 and 3.1) confirmed the presence of a C-terminal amidation motif
      whereas that of aurein 5.3 did not. Processed peptides corresponding in molecular
      mass to aureins 2.2, 2.3, 2.5, 3.1 and 5.3 were identified in the same secretion
      sample using LC/MS. The application of this technique thus permits parallel
      peptidomic and transcriptomic analyses on the same lyophilized skin secretion
      sample circumventing sacrifice of specimens of endangered herpetofauna.

PMID- 15721492
TI  - Meta-analysis of possible external triggers of acute myocardial infarction.
AB  - BACKGROUND: Although it is well known that the acute myocardial infarction can be
      triggered by events such as physical activity, emotional stress, sexual activity
      or eating, the observed frequencies of these events preceding the onset of
      myocardial infarction vary between published reports. METHODS: A meta-analysis of
      17 seldom population-based studies that included data on frequency of external
      triggers or onsets during sleep was performed. In each analysis, the data were
      combined only from the studies reporting on a particular trigger. RESULTS: Of the
      10519 patients, heavy physical activity was recorded before the onset of
      myocardial infarction in 6.1%, whereas mild-to-moderate physical activity was
      recorded in 28.6% of 7517 patients. Eating preceded the onset in 8.2% of 4785
      patients, various kinds of emotional stress in 6.8% of 2565 (particularly anger
      in 2.1% of 2283), meteorologic stress in 3.7% of 3371, and sexual activity in
      1.1% of 3406 patients. Out of 11778 patients, 20.7% had infarction onset during
      sleep. Triggers in general (OR = 1.45, 95%CI = 1.21-1.76; p < 0.0001), heavy
      physical activity (OR = 6.21, 95%CI = 3.77-10.23; p < 0.0001) and eating (OR =
      1.70, 95%CI = 1.14-2.53; p = 0.0008) were more likely to precede the infarction
      onset in men while women were more likely to report emotional stress (OR = 0.66,
      95%CI = 0.50-0.86; p = 0.002). CONCLUSIONS: The present meta-analysis defines the
      occurrence of possible external triggers before the onset of myocardial
      infarction in general population, but their actual contribution to the very onset
      is somewhat less frequent. Future investigation should identify other eventual
      triggers unrecognized as yet, asses the risk of triggering myocardial infarction
      among patients with defined levels of ischemic heart disease or plaque
      vulnerability, and further elucidate the pathophysiologic mechanisms of gender
      differences and beneficial effect of habitual physical activity.

PMID- 15721493
TI  - Drug-eluting stents: results, promises and problems.
AB  - In-stent restenosis is the major drawback of percutaneous coronary interventions,
      occurring in 10-40% of the patients. Recently, new stents have emerged which are
      loaded with anti-inflammatory, anti-migratory, anti-proliferative or pro-healing
      drugs. These drugs are supposed to inhibit inflammation and neointimal growth and
      subsequently in-stent restenosis. In this review article the results of human
      clinical studies investigating drug-eluting stents are discussed from a clinical
      point of view, focussing on the efficacy in the prevention of restenosis and
      their potential side effects. Both success and failure in the field of drug
      eluting stents have been described. Successful devices are the sirolimus-eluting
      and the polymer-based paclitaxel-eluting stents. Potentially dangerous side
      effects of drug-eluting stents are adverse drug interactions, incomplete stent
      apposition and increased in-stent thrombosis rates. Demonstration of long-term
      efficacy is mandatory since in some animal studies a delayed healing has been
      observed. Currently, the successful drug-eluting stents are under investigation
      in all types of lesions. We conclude that the results with some drug-eluting
      stents are promising, but further evidence on long-term efficacy and safety, also
      in high-risk subgroups, is needed.

PMID- 15721494
TI  - Normal angiogram in acute coronary syndrome-preangiographic risk stratification,
      angiographic findings and follow-up.
AB  - BACKGROUND: Coronary angiographies performed during acute coronary syndrome show
      different coronary morphologies-vessel occlusions, thrombi and various types of
      stenoses. In a few cases of acute coronary syndrome, angiography reveals normal
      coronary arteries. It is the purpose of this study to analyze this specific
      subset of patients who presented with an acute coronary syndrome but had a normal
      coronary angiogram with respect to the preangiographic diagnostics, risk
      stratification and clinical follow-up. METHODS AND RESULTS: A total of 897
      coronary angiographies were performed as an emergency procedure in our
      institution. The majority of patients (n = 821) presented with coronary artery
      disease and the majority was treated by mechanical revascularization (86.3%). In
      76 patients (8.5%), no coronary artery stenosis was documented. However,
      according to the preangiographic risk stratification, coronary artery disease was
      expected in these patients. Observations documented angiographically included
      coronary spasms (6.6%) and muscle bridges (5.3%). During a mean follow-up of 11.2
      +/- 6.4 months, one patient developed an acute myocardial infarction requiring
      coronary intervention. All other patients were free of any cardiac event.
      CONCLUSIONS: In summary, we have to consider that coronary angiography may not
      always detect the cause of myocardial ischemia in every patient. There is a small
      group of patients with normal coronary angiograms during acute coronary syndrome.
      Additional diagnostic procedures like intravascular ultrasound (IVUS) or the
      assessment of intracoronary physiological parameters may increase the diagnostic
      value of angiography.

PMID- 15721495
TI  - Normal angiogram in patients with acute coronary syndrome: searching for unusual
      substrates of myocardial ischemia.

PMID- 15721496
TI  - Comparison of transprosthetic mean pressure gradients between Medtronic Hall and
      ATS valves in the aortic position.
AB  - AIM OF THE STUDY: Several studies have shown the inferior performance of small
      prostheses in the narrow aortic root. However, modern low-profile mechanical
      prostheses have improved hemodynamic performance characteristics. By measuring
      the transprosthetic pressure gradient in vivo, we were able to characterize the
      hemodynamic features of two prostheses: the ATS Medical (ATS) and the Medtronic
      Hall (MH) valves. METHODS: From October 1994 to April 2002, 113 patients received
      an aortic valve replacement (AVR) with either an ATS or a MH valve. The
      transprosthetic pressure gradients, calculated from a simplified Bernoulli
      equation during immediate postoperative Doppler echocardiographic examination,
      were compared for differently sized prostheses with respect to body surface area
      (BSA). RESULTS: The mean pressure gradients and the mean BSAs were: 27.8 +/- 14.8
      mm Hg and 1.50 +/- 0.10 m(2) in ATS 19 mm (n = 7), 20.4 +/- 8.5 mm Hg and 1.54 +/
      0.11 m(2) in ATS 21 mm (n = 22), 13.0 +/- 5.7 mm Hg, 1.70 +/- 0.13 m(2) in ATS
      23 mm (n = 22), 10.9 +/- 3.5 mm Hg and 1.81 +/ -0.16 m(2) in ATS 25 mm (n = 19),
      9.3 +/- 0.6 mm Hg and 1.72 +/- 0.17 m(2) in ATS 27 mm (n = 4), 13.5 +/- 6.5 mm Hg
      and 1.54 +/- 0.13 m(2) in MH 20 mm (n = 9), 10.9 +/- 4.7 mm Hg and 1.64 +/- 0.15
      m(2) in MH 22 mm (n = 22), 9.3 +/- 3.1 mm Hg and 1.72 +/- 0.12 m(2) in MH 24 mm
      (n = 7). CONCLUSIONS: With the exception of the ATS 19-mm valve, the variously
      sized prostheses have acceptable transprosthetic pressure gradient measurements.
      In addition, even-sized MH valves (20 and 22 mm) with a thinner sewing cuff
      showed better hemodynamic performances than similarly sized ATS valves.

PMID- 15721497
TI  - Guidelines for implementation of patient self-testing and patient self-management
      of oral anticoagulation. International consensus guidelines prepared by
      International Self-Monitoring Association for Oral Anticoagulation.
AB  - AIMS: This document provides health care professionals involved in initiating and
      monitoring oral anticoagulation therapy with guidelines for the provision of safe
      and effective patient self-testing/patient self-management of oral
      anticoagulation. METHODS AND RESULTS: The consensus group has critically reviewed
      the literature and compared the results of usual care (UC) vs. anticoagulation
      clinic and patient self-management/patient self-testing (PSM/PST). The education
      and training of patients for self-monitoring are described, together with the
      suitability of patients, the effect on quality of life and cost-effectiveness.
      The consensus agrees that patient self-testing and patient self-management are
      effective methods of monitoring oral anticoagulation therapy, providing outcomes
      at least as good as, and possibly better than, those achieved with an
      anticoagulation clinic. All patients must be appropriately selected and trained.
      Currently available self-testing/self-management devices give INR results which
      are comparable with those obtained in laboratory testing. The most frequent
      testing frequency is weekly but lower frequency of testing can be justified based
      on institutional or patient conditions. CONCLUSIONS: The consensus agrees that
      there are several points in favour of PST/PSM, for example, a higher degree of
      medical safety, increased patient education, improved response to changes in
      lifestyle, increased independence for the patient and improved quality of life.

PMID- 15721498
TI  - Long-term (> 8 weeks) home inotropic therapy as destination therapy in patients
      with advanced heart failure or as bridge to heart transplantation.

PMID- 15721499
TI  - Reducing atrial tachycardia and atrial fibrillation episodes with a prevention
      and treatment device and tailored treatment.
AB  - BACKGROUND: Pacemaker treatment of known trigger mechanisms for atrial
      tachyarrhythmias (AT) and atrial fibrillation (AF) has shown reduction in the
      incidence of AF. A new arrhythmia management device, which included storage of
      AT/AF (for tailoring treatment) and three prevention algorithms and one for
      treatment, was examined in order to identify the influence on arrhythmia episodes
      over a 12-month follow-up (FU) period. METHODS: Twenty-three consecutive patients
      with known tachybradyarrhythmias were examined. Seven patients had to be excluded
      (two outliers, four developed permanent AF, one had no detection algorithm turned
      on at implantation). The remaining 16 patients showed 2723 episodes (675 treated
      episodes) for evaluation of the effect on episodes/month/patient (e/m/p),
      treatment success, duration of episodes, circadian distribution and quality of
      life. RESULTS: The AT/AF e/m/p were reduced from 37 +/- 102 e/m/p at 1-month FU
      to 16 +/- 48 e/m/p at 3-month FU, 15 +/- 48 e/m/p at 6-month FU and 10 +/- 28
      e/m/p at 12-month FU (p < 0.05), according to fewer subjective symptoms.
      Treatment success remained stable during the observation period (29-40%). Only
      minor changes in the duration of episodes and the distribution of start times
      were observed. CONCLUSION: Tailoring treatment by the pacemaker examined with
      several prevention and treatment algorithms reduces e/m/p and might be a
      promising supplement in the treatment of selected patients with known AT/AF and
      bradycardia.

PMID- 15721500
TI  - Simple electrocardiographic markers for the prediction of paroxysmal atrial
      fibrillation in hyperthyroidism.
AB  - BACKGROUND: Hyperthyroidism is a major cause of paroxysmal atrial fibrillation
      (AF). The purpose of this study was to evaluate the predictors of AF in the
      patients with clinical and subclinical hyperthyroidism. METHODS AND RESULTS: The
      study population consisted of four groups: group I (57 euthyroid healthy
      persons), group II (33 patients with subclinical hyperthyroidism), group III (69
      patients with overt hyperthyroidism) and group IV (31 patients with overt
      hyperthyroidism and documented paroxysmal AF). The maximum P wave duration (P
      maximum) in group IV (114 +/- 8 ms) was significantly higher than group I (102 +/
      7 ms, p < 0.001), group II (106 +/- 7 ms, p < 0.001) and group III (108 +/- 9
      ms, p0.005). The P wave dispersion (PWD) was measured as 46 +/- 9 ms in group IV
      and this was significantly higher than group I (29 +/- 8 ms, p < 0.001), group II
      (36 +/- 9 ms, p < 0.001) and grup III (38 +/- 8 ms, p = 0.001). The P maximum and
      PWD were higher in the patients with subclinical hyperthyroidism compared to
      healthy individuals. Univariate regression analysis revealed that age, P maximum
      and PWD, multivariate analysis showed that P maximum and PWD were significant
      predictors of paroxysmal AF. A PWD value of 37.5 ms separated group IV from
      others with a sensitivity of 90%, specificity of 85%, and positive predictive
      accuracy of 77%. CONCLUSION: Simply measuring P maximum and PWD values, we could
      identify the patients with high risk for the development of AF and these simple
      ECG parameters may help in clinical judgement to determine the requirement for
      treatment in the patients with subclinical hyperthyroidism.

PMID- 15721501
TI  - Egg consumption and endothelial function: a randomized controlled crossover
      trial.
AB  - BACKGROUND: Because of egg cholesterol content, reduction in egg consumption is
      generally recommended to reduce risk of cardiovascular disease. Recently,
      however, evidence has been accumulating to suggest that dietary cholesterol is
      less relevant to cardiovascular risk than dietary saturated fat. This randomized
      controlled crossover trial was conducted to determine the effects of egg
      ingestion on endothelial function, a reliable index of cardiovascular risk.
      METHODS: Forty-nine healthy adults (mean age 56 years, 40% females) underwent a
      baseline brachial artery reactivity study (BARS), and were assigned to two eggs
      or oats daily for 6 weeks in random sequence with a 4-week washout. A BARS was
      done at the end of each treatment phase, measuring flow-mediated vasodilation
      (FMD) in the brachial artery using a high-frequency ultrasound. RESULTS: FMD was
      stable in both egg and oat groups, and between-treatment differences were not
      significant (egg -0.96%, oatmeal -0.79%; p value >0.05). Six weeks of egg
      ingestion had no effect on total cholesterol (baseline: 203.8 mg/dl; post
      treatment: 205.3) or LDL (baseline: 124.8 mg/dl; post-treatment: 129.1). In
      contrast, 6 weeks of oats lowered total cholesterol (to 194 mg/dl; p = 0.0017)
      and LDL (to 116.6 mg/dl; p = 0.012). There were no differences in body mass index
      (BMI), triglyceride, HDL or SBP levels between egg and oat treatment assignments.
      CONCLUSION: Short-term egg consumption does not adversely affect endothelial
      function in healthy adults, supporting the view that dietary cholesterol may be
      less detrimental to cardiovascular health than previously thought.

PMID- 15721502
TI  - Management of acute coronary syndromes, a questionnaire survey of the clinical
      practice of cardiologists and other medical physicians belonging to west midland
      hospitals.
AB  - OBJECTIVE: To assess the management of acute coronary syndromes by cardiologists
      and other medical physicians in a clinical setting. DESIGN: Questionnaire survey
      consisting of 10 hypothetical clinical scenarios and four possible therapeutic
      options for each scenario. SETTING: Consultants and specialist registrars in
      Cardiology (with or without access to interventional facilities) and consultant
      physicians belonging to various hospitals in the west midland region of United
      Kingdom. MAIN OUTCOME MEASURES: Respondents' ability to recognise high risk
      patients and their management of the hypothetical clinical cases. To establish
      any differences in management strategy between cardiologists and general
      physicians, and whether these differences, if any, relate to access to
      interventional cardiac facilities. RESULTS: Overall no significant differences
      were found in the responses between cardiologists and general physicians with or
      without access to cardiac interventional facilities. However, cardiologists were
      more inclined to use percutaneous transluminal coronary angioplasty (PTCA)
      compared to other physicians (scenario 8, 18.4% vs. 6.7%, p = 0.05 and scenario
      9, 44.9% vs. 26.7%, p = 0.01). In two other situations, physicians from
      institutions with access to interventional facilities were more inclined to use
      'other' treatment strategies (intravenous nitrates, antiplatelet treatment,
      inotropes, Intra-aortic balloon pump) compared to their colleagues from non
      tertiary hospitals with no interventional facility on site (scenario 3, 21.7% vs.
      2.4%, p = 0.04) and more use of PTCA ( scenario 6, 52.2% vs. 26.8%, p = 0.04).
      CONCLUSIONS: The management of acute coronary syndromes in this questionnaire
      survey was satisfactory and evidence based. No real differences were found
      between the management strategies adopted by cardiologists or non-cardiologists.
      Physicians working in centres with interventional facilities were no more
      inclined towards using primary PTCA or rescue angioplasty than those working in
      centres without such facilities.

PMID- 15721503
TI  - Role of endogenous interleukin-10 production and lipid peroxidation in patients
      with acute myocardial infarction treated with primary percutaneous transluminal
      coronary angioplasty, interleukin-10 and primary angioplasty.
AB  - BACKGROUND: Currently available evidence suggests a potentially protective role
      for interleukin (IL)-10 in atherosclerosis. Reactive oxygen species, such as
      superoxide anion, hydrogen peroxide, peroxynitrite, and hydroxyl radical, seem to
      play a pivotal role in the pathogenesis of ischemia-reperfusion injury. The aim
      of this study was to assess whether a rise in lipid peroxidation (LPx), as
      malondialdehyde (MDA) and 4 hydroxyalkenal (4-HNE), during acute myocardial
      infarction (AMI) is associated with serum concentrations of IL-10. METHODS: A
      total of 50 patients diagnosed with AMI and 50 control subjects were studied.
      Primary angioplasty was performed in the 50 patients with an indication for
      reperfusion. Serum IL-10 and LPx (MDA + 4-HNE) concentrations were measured using
      commercially available enzyme-immunoassays. The venous blood samples were taken
      90 +/- 35 min after having obtained a TIMI III flow in patients with AMI. In
      control subjects, blood samples were taken at the time of admission to hospital.
      RESULTS: IL-10 concentrations were higher in patients with AMI compared with
      control subjects (32.45 +/- 2.17 vs. 22.10 +/- 2.40 pg/ml; P = 0.03). Serum LPx
      concentrations were higher in the AMI group (22.20 +/- 3.63 vs. 11.90+/-1.26
      microM; P=0.01). IL-10 levels in patients with AMI were significantly correlated
      with the concentrations of LPx (Pearson's r =0.49, P = 0.02). CONCLUSIONS: Our
      results provide evidence that (1) IL-10 is increased in a human model of
      myocardial ischemia-reperfusion and (2) reperfusion injury and elevated IL-10
      levels are related in patients with AMI treated with primary percutaneous
      transluminal coronary angioplasty.

PMID- 15721504
TI  - Effectiveness and safety of the thrombolytic therapy for acute pulmonary
      thromboembolism: results of a multicenter registry in the Japanese Society of
      Pulmonary Embolism Research.
AB  - OBJECTIVE: To assess the effectiveness and safety of thrombolytic treatment for
      acute pulmonary thromboembolism (APTE), especially in the hemodynamically stable
      patients with right ventricular afterload stress. METHODS AND RESULTS: In a total
      of 221 patients with APTE, the association between thrombolytic treatment and the
      clinical outcomes were investigated. Thrombolysis was given to 121 patients
      (Thrombolytic Group), and the remaining 100 patients were treated with
      anticoagulation alone (Anticoagulation Group). In both patients with prolonged
      shock and patients who were hemodynamically stable without right ventricular
      afterload stress, the rate of death and recurrence of APTE in Anticoagulation
      Group were similar to those in Thrombolytic Group. In patients with right
      ventricular afterload stress, better outcomes were observed in Thrombolytic Group
      than in Anticoagulation Group, although the difference did not reach statistical
      significance. There was no significant difference in the rate of major bleeding
      episode between these two groups. CONCLUSION: Our results suggested that
      performing thrombolytic treatment in APTE patients with right ventricular
      afterload stress should be considered even in Japan.

PMID- 15721505
TI  - Efficacy and optimal dose of sildenafil in primary pulmonary hypertension.
AB  - PURPOSE: We aimed to assess the effects of sildenafil and evaluate optimal dosing
      in primary pulmonary hypertension (PPH). Sildenafil selectively inhibits
      phosphodiesterase 5 (PDE5), which is abundant in pulmonary and penile tissue.
      This results in increasing nitric oxide (NO) at tissue level leading to pulmonary
      vasodilatation. SUBJECTS AND METHODS: Our study was a prospective study of
      sildenafil in 15 consecutive patients with severe symptomatic PPH of NYHA class
      III-IV. All patients were stabilized for a minimum period of 5 days with
      antifailure medications. Sildenafil was started at 50 mg twice daily for 4 weeks
      and increased to 100 mg bid for 4 more weeks in a step-up protocol. Primary end
      points were change in Borg dyspnea index, NYHA class and 6-min walk distance,
      estimated at baseline 1, 2, 4 and 8 weeks. RESULTS: NYHA class (baseline 3.8 +/-
      0.4 vs. 4 weeks 2.4 +/- 0.5, p = 0.002), Borg dyspnea index (8.1 +/- 1.7 vs. 4.4
      +/- 1.9, p = 0.0007), 6-min walk distance (234 +/- 44 vs. 377 +/- 128 m, p =
      0.001) and Pulmonary artery pressure (125 +/- 15 vs. 113 +/- 18 mm Hg p = 0.05)
      are significantly improved with sildenafil 50 mg bid at 4 weeks. Increasing the
      dose to 100 mg bid did not produce further benefit. Echocardiography parameters
      of right heart dimensions and functions did not change markedly in the study
      period. CONCLUSION: Sildenafil is well tolerated with no adverse effects in
      severe pulmonary hypertension. It reduces symptoms, improves effort tolerance and
      controls refractory heart failure significantly by 2 weeks in 70% of patients at
      50 mg twice daily. Three patients (20%) failed to respond with sildenafil.

PMID- 15721506
TI  - Angiotensin-converting enzyme gene deletion polymorphism modulation of onset of
      symptoms and survival rate of patients with heart failure.
AB  - BACKGROUND: Angiotensin-converting enzyme is involved in the pathophysiology of
      heart failure. We hypothesized that clinical characteristics as well as survival
      rate in patients with heart failure of different etiologies may be modulated by
      functional variants DD, ID and II of the angiotensin-converting enzyme gene.
      METHODS: We studied 333 patients with heart failure, aged 43.3 +/- 10.5 years,
      262 (78.7%) men and 71 (21.3%) women. Heart failure was ascribed to idiopathic
      dilated cardiomyopathy in 125 patients. Heart failure was caused by ischemic
      heart disease in 63 patients, Chagas' disease in 58, hypertensive heart disease
      in 41, alcoholic cardiomyopathy in 24, and was due to other etiologies in 22
      patients. Statistical analysis was performed with the chi(2) test, Student's t
      test, analysis of variance, Kaplan-Meier and Cox proportional hazards methods.
      RESULTS: The DD genotype was associated with increased systolic left ventricular
      diameter (p = 0.031). Earlier onset of symptoms was observed in patients with
      alcoholic cardiomyopathy and DD genotype (p = 0.033, codominant D) and in
      patients with hypertensive cardiomyopathy and DD genotype (p = 0.048, codominant
      D; p = 0.024, recessive D). Mortality was higher in patients older than 50 years
      with DD genotype (p = 0.007, codominant D; p = 0.002, recessive D). Variables
      independently associated with higher mortality in patients older than 50 years
      were age, diabetes mellitus, Chagas' disease etiology and DD genotype.
      CONCLUSIONS: These results add evidence for an association of the DD genotype of
      the angiotensin-converting enzyme gene with earlier onset of symptoms and
      decreased survival rate of selected patients with heart failure.

PMID- 15721507
TI  - Change with exercise in QT dispersion in infarct-related myocardium after
      angioplasty.
AB  - BACKGROUND: The aim of this study was to evaluate the relationship between
      exercise-induced QT dispersion and condition of infarct-related myocardium
      including myocardial scar after angioplasty assessed with exercise perfusion
      single photon emission computed tomography (SPECT). METHODS: Exercise thallium
      201 SPECT was performed 6 months after successful direct angioplasty in 67 male
      patients (60.6 +/- 11.5 years), who had Q wave infarction resulting from single
      vessel disease, and the number of perfusion defect areas (DS) was measured at
      rest and exercise together with QT (QTc) dispersion. RESULTS: In 52 patients with
      resting perfusion defects, the exercise-induced change in DS was correlated to
      the change in QT (or QTc) dispersion (r = -0.51 or r = -0.531, p < 0.0001). When
      the patients were grouped according to the patterns of transient perfusion
      defect, there were significant differences in DeltaQT dispersion and DeltaQTc
      dispersion among infarct-related three groups (reverse, fixed, and partial
      redistributions) and normal volunteers (DeltaQT dispersion; -5.7 +/- 12.7 ms in
      13 patients with reverse redistribution, -16.3 +/- 13.1 ms in 30 patients with
      fixed redistribution, -28.9 +/- 29.5 ms in 9 patients with partial
      redistribution, and +3.4 +/- 20.9 ms in 12 normal volunteers, p = 0.0098;
      DeltaQTc dispersion; +18.2 +/- 20.8 ms, +1.4 +/- 16.7 ms, -15.4 +/- 30 ms, and
      +19 +/- 27.5 ms, p = 0.0017, respectively). DeltaQTc dispersion estimated the
      SPECT image patterns (p = 0.0002) with a sensitivity of 67.3%, a specificity of
      83.7% and an accuracy of 78.2%. CONCLUSIONS: The change with exercise in QT
      dispersion may help detect the condition of infarct-related myocardium after
      angioplasty.

PMID- 15721508
TI  - Left atrial function, cytokines and soluble apoptotic markers in mitral stenosis:
      effects of valvular replacement.
AB  - BACKGROUND: Patients with mitral stenosis (MS) and heart failure (HF) are
      characterized by changes in the left atrial (LA) function and activation of the
      apoptotic process. The purpose of the present study was the evaluation of the
      effect of mitral valve replacement on the LA function, on inflammatory process
      and apoptotic markers in patients with MS and HF. METHODS: We studied 30 patients
      with MS and HF (15 in NYHA III-IV and 15 in NYHA IV) in sinus rhythm (mean age
      56.2 +/- 4.6 years), and 20 age and gender matched healthy volunteers. Blood
      samples were obtained before and 6 months after surgical mitral valve
      replacement, and plasma levels of soluble Fas/APO-1 receptor (sFas), tumor
      necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were measured.
      Echocardiographically, LA volumes were measured at mitral valve opening (Vmax),
      at the onset of left atrial systole (P wave of the electrocardiogram, Vp) and at
      the mitral valve closure (Vmin). LA contractile function was assessed by the LA
      active emptying fraction (ACTEF). RESULTS: After mitral valve replacement, TNF-a,
      IL-6 and sFas levels, as well as the Vmax LA volume, were significantly reduced
      (p < 0.05). ACTEF showed a significant postoperative decrease (0.29 +/- 0.09 vs.
      0.23 +/- 0.06, p < 0.01) and it was significantly correlated with sFas (r = 
      0.88, p = 0.001), TNF-a (r = -0.81, p = 0.001) and IL-6 (r = -0.74, p = 0.001)
      levels. CONCLUSION: The present findings indicate that mitral valve replacement
      in patients with mitral valve stenosis, reduces the size of the left atrium,
      improves left atrial contractile function and depresses inflammatory and
      apoptotic process.

PMID- 15721510
TI  - Disproportionate increase in prevalence of diabetes among patients with
      congestive heart failure due to systolic dysfunction.
AB  - BACKGROUND: Despite new therapies, the prevalence of heart failure continues to
      escalate. The prevalence of diabetes, a risk factor for heart failure, also
      continues to rise. To further understand the increasing prevalence of heart
      failure, we compared trends in the prevalence of diabetes among individuals with
      diagnosed heart failure versus those in the general population. METHODS: Fourteen
      randomized trials between 1989 and 1999 including subjects with heart failure (n
      = 34,633) were reviewed. For each trial, the enrollment date was used to estimate
      the yearly prevalence of diabetes among study participants with heart failure.
      The prevalence of diabetes in the general population was estimated based on
      United State's Center for Disease Control statistics from 1989 to 1999. The
      prevalence of diabetes between heart failure subjects and the general population
      was compared using a two-sample t-test for independent samples with unequal
      variances. RESULTS: The prevalence of diabetes increased from 2.6% to 4.0% from
      1989 to 1999 in the general U.S. population. Among patients with heart failure,
      the prevalence of diabetes increased from 13% to 47%. Diabetes prevalence
      estimates varied significantly (p < 0.001) between the general population and
      individuals with heart failure during the study period. CONCLUSIONS: The rising
      prevalence of diabetes may partially explain the growing epidemic of heart
      failure. Increased efforts targeting diabetes and other cardiovascular risk
      factors are warranted in attenuating the rising prevalence of heart failure.

PMID- 15721509
TI  - Death and hospitalization in heart failure patients receiving carvedilol vs.
      metoprolol tartrate.
AB  - BACKGROUND: The Carvedilol or Metoprolol European Trial (COMET) demonstrated
      improved survival with carvedilol vs. metoprolol tartrate in patients with heart
      failure. The benefits of carvedilol in typical clinical practice in the United
      States are unknown. METHODS: Using data from a large United States health
      insurance claims database, we conducted a retrospective study to compare the
      risks of death and hospitalization and the cost of inpatient care in heart
      failure patients receiving carvedilol vs. metoprolol tartrate. The sample
      consisted of all patients with a prescription for carvedilol or metoprolol
      tartrate between September 1997 and August 2000 who also had a prior medical
      encounter with a primary diagnosis of heart failure, prior prescriptions for a
      loop diuretic and an angiotensin-converting enzyme inhibitor, and no prior
      prescriptions for a beta-blocker. RESULTS: We identified 887 carvedilol patients
      and an equal number that received metoprolol tartrate. Mean duration of follow-up
      was 11 months (maximum, 36 months). Controlling for baseline characteristics
      using a Cox proportional hazards model, carvedilol was independently associated
      with a reduced risk of all-cause mortality (hazard ratio 0.78; 95% confidence
      interval 0.61 to 0.99) and all-cause hospitalization (hazard ratio 0.77; 95%
      confidence interval 0.67 to 0.90). In a propensity-matched sample of carvedilol
      and metoprolol tartrate patients (n = 564 each), expected costs of inpatient care
      at 36 months were 10,509 US dollars lower with carvedilol (95% confidence
      interval 2934-18,085 US dollars). CONCLUSIONS: Use of carvedilol rather than
      metoprolol tartrate may improve survival and reduce costs of care in heart
      failure patients in typical clinical practice in the United States.

PMID- 15721511
TI  - Diaphragmatic paralysis caused by malposition of chest tube placement after
      pediatric cardiac surgery.
AB  - Diaphragmatic paralysis is a recognized complication after pediatric cardiac
      surgery. It is universally acknowledged that direct phrenic nerve injury during
      surgery is the etiology. However, we experienced two unusual cases of
      diaphragmatic paralysis following malposition of chest tube placement after
      pediatric cardiac surgery. The malposition of too deeply placed chest tube with
      resultant phrenic nerve injury was presumably the underlying cause. One patient
      underwent successful diaphragmatic plication due to intractable respiratory
      distress. The other was asymptomatic. Our report highlights the previously
      unreported complication of chest tube-induced phrenic nerve injury following its
      malposition after pediatric cardiac surgery. Prompt recognition and correction of
      tube malposition or selection of a softer chest tube probably can ameliorate the
      problem.

PMID- 15721512
TI  - Left main and saphenous vein graft spasm: an unusual association.
AB  - We present a case of left main spasm which was associated with spasm of a
      saphenous vein graft. This case emphasizes the importance of excluding an
      excessive vasoconstrictory response in patients treated with percutaneous
      coronary interventions.

PMID- 15721513
TI  - Alleviation of hemolysis after the stent implantation into an obstructed
      extracardiac conduit.
AB  - An 11-year-old boy who had undergone extracardiac conduit repair for the
      corrected transposition of the great arteries at 1 year of age showed hemolytic
      anemia due to a significant stenosis of the conduit placed between the right
      ventricle and pulmonary artery. There was a pressure gradient of 157 mmHg across
      the stenosis, giving 1.6:1 of right to left ventricular pressure ratio.
      Hemoglobin was 93 g/L with increased serum lactate dehydrogenase of 1382 IU/L.
      Stent implantation into this obstructed conduit has decreased a pressure gradient
      to 45 mmHg, leaving 0.74 of right to left ventricular pressure ratio. At 3 months
      after the stent implantation, hemoglobin has normalized. This case illustrate
      that an extremely severe stenosis of the right ventricular extracardiac conduit
      can induce hemolytic anemia and stent implantation into the conduit can be one of
      the alternative treatments to alleviate conduit stenosis and stop hemolysis.

PMID- 15721514
TI  - Acute neurological events in a patient with secondary polycythaemia and
      arteriovenous malformations.
AB  - General internists and adult cardiologist are seeing adult congenital heart
      disease more frequently in their clinical practices. We report the case of a
      polycythaemic patient with the cerebral and pulmonary arteriovenous malformations
      (AVMs) who presents with a transient ischaemic attack (TIA). Treatment strategies
      such as antiplatelet drugs and vensection may at best be ineffective and at worst
      detrimental to the patient.

PMID- 15721515
TI  - Pulmonary function after percutaneous coronary intervention and bypass surgery.

PMID- 15721516
TI  - Endovascular foreign body retrieval from right side of the heart: a case series
      of six patients.

PMID- 15721517
TI  - Not all statins are alike: induced rhabdomyolysis on changing from one statin to
      another one.
AB  - A 59-year-old woman underwent orthotopic heart transplantation 4 years earlier.
      At the time of transplantation, she was receiving pravastatin at a dose of 20 mg
      per day; she tolerated subsequent combination with immunosuppression
      (cyclosporine A, prednisone, mycophenolate mofetil) very well throughout the 4
      years. After switching from pravastatin to simvastatin, she developed severe
      muscular weakness and laboratory evidence of muscle break down. Biochemical
      markers of rhabdomyolysis did not subside until after repeat hemodialysis and
      normalized after 2 months in conjunction with improved renal function. Clinical
      improvement was not apparent until after 5 months.

PMID- 15721518
TI  - Heart rate variability in adult patients with isolated left ventricular
      noncompaction.
AB  - BACKGROUND: Isolated left venticular noncompaction (IVNC) is a rare congenital
      heart disease charactrized by a pattern of an excessively prominent trabecular
      meshwork with deep intertrabecular recesses. Heart rate variability (HRV) has
      been reported to be impaired in various heart diseases, though little is known
      regarding HRV in adult patients with IVNC. METHODS: We measured spectral
      components of HRV using fast Fourier transformation of 24-h Holter recordings in
      10 adult patients with IVNC, 40 patients with myocardial infarction (MI), 40
      patients with hypertrophic cardiomyopathy (HCM) and 40 healthy controls. RESULTS:
      The low frequency component and the high frequency component of HRV were lower in
      IVNC patients tahn those in controls (265 +/- 213 ms(2) vs. 469 +/- 195 ms(2), p
      < 0.01; 80 +/- 51 ms(2) vs. 185 +/- 126 ms(2), p < 0.01). Furthermore, 3 IVNC
      patients with a previous history of heart failure exhibited more decreased HRV
      (low frequency, 75 +/- 56 ms(2); high frequency, 39 +/- 18 ms(2)). Contrary, the
      ratio of low frequency to high frequency component was higher in patients with
      IVNC than controls (3.5+/-0.5 vs. 3.2 +/- 0.3, p < 0.05). The degree of impaired
      HRV was severest in MI patients, intermediate in IVNC patients and mildest in HCM
      patients compared with controls. CONCLUSIONS: HRV is impaired in adult patients
      with IVCN, especially in patients with a previous history of heart failure,
      suggesting vagal withdrawal or sympathetic enhancement. HRV in IVNC adults is
      less impaired than in MI patients, and more impaired than in HCM patients of our
      cohort.

PMID- 15721519
TI  - Double jeopardy: two possible causes of sudden death in a previously healthy man.
AB  - A case of the simultaneous occurrence of two rare causes of sudden death is
      reported. A previously healthy man was shown to have anomalous coronary
      circulation, with the left main coronary artery coursing between the great
      arteries, and Brugada syndrome raising the possibility of an association between
      these findings.

PMID- 15721520
TI  - Brugada syndrome simulating acute myocardial infarction.

PMID- 15721521
TI  - Non-invasive, three-dimensional visualization of coronary artery bypass grafts by
      multislice spiral computed tomography.

PMID- 15721522
TI  - Effect of acute hyperinsulinemia on ventricular repolarization in uncomplicated
      obesity.
AB  - BACKGROUND: Acute hyperinsulinemia has been shown to increase QTc interval in
      lean subjects, but data on obese subjects are still unclear. Aim of this study
      was to evaluate the effect of acute hyperinsulinemia on QTc interval and QTc
      dispersion in uncomplicated obesity. METHODS: We calculated QTc duration and QTc
      dispersion in 30 uncomplicated obese subjects (mean age 32.2 +/- 7, BMI 36.7 +/-
      9.4 kg/m(2)) by measurements of 12-lead ECG recording during a euglycemic
      hyperinsulinemic clamp. RESULTS: Insulin infusion during the clamp did not
      significantly modify QTc interval and QTc dispersion in uncomplicated obese
      subjects (401.5 +/- 29.2 vs. 413.7 +/- 30.5; 35.4 +/- 10.5 vs. 38.7 +/- 14.5,
      respectively). CONCLUSIONS: Acute hyperinsulinemia seems to no significantly
      affect ventricular repolarization in uncomplicated obesity. Insulin resistance
      and the absence of diabetes and hypertension could explain, at least in part,
      this finding.

PMID- 15721523
TI  - Safety assessment methodology in management of spent sealed sources.
AB  - Environmental hazards can be caused from radioactive waste after their disposal.
      It was therefore important that safety assessment methodologies be developed and
      established to study and estimate the possible hazards, and institute certain
      safety methodologies that lead and prevent the evolution of these hazards. Spent
      sealed sources are specific type of radioactive waste. According to IAEA
      definition, spent sealed sources are unused sources because of activity decay,
      damage, misuse, loss, or theft. Accidental exposure of humans from spent sealed
      sources can occur at the moment they become spent and before their disposal.
      Because of that reason, safety assessment methodologies were tailored to suit the
      management of spent sealed sources. To provide understanding and confidence of
      this study, validation analysis was undertaken by considering the scenario of an
      accident that occurred in Egypt, June 2000 (the Meet-Halfa accident from an
      iridium-192 source). The text of this work includes consideration related to the
      safety assessment approaches of spent sealed sources which constitutes assessment
      context, processes leading an active source to be spent, accident scenarios,
      mathematical models for dose calculations, and radiological consequences and
      regulatory criteria. The text also includes a validation study, which was carried
      out by evaluating a theoretical scenario compared to the real scenario of Meet
      Halfa accident depending on the clinical assessment of affected individuals.

PMID- 15721524
TI  - An advanced approach to reactivity rating.
AB  - Reactive hazards remain a significant safety challenge in the chemical industry
      despite continual attention devoted to this problem. The application of various
      criteria, which are recommended by the guidelines for assessment of reactive
      hazards, often causes unsafe results to be obtained. The main origins of such
      failures are as follows: (a) reactivity of a compound is considered as an
      inherent property of a compound; (b) some appropriate criteria are determined by
      using too simple methods that cannot reveal potential hazards properly. Four well
      known hazard indicators--time to certain conversion limit, TCL; adiabatic time to
      maximum rate, TMR; adiabatic temperature rise; and NFPA reactivity rating number,
      Nr--are analyzed in the paper. It was ascertained that they could be safely used
      for preliminary assessment of reactive hazards provided that: (a) the selected
      indicator is appropriate for the specific conditions of a process; (b) the
      indicators have been determined by using the pertinent methods. The applicability
      limits for every indicator were determined and the advanced kinetics-based
      simulation approach, which allows reliable determination of the indicators, is
      proposed. The technique of applying this approach is illustrated by two practical
      examples.

PMID- 15721525
TI  - Explosive decomposition of ethylene oxide at elevated condition: effect of
      ignition energy, nitrogen dilution, and turbulence.
AB  - Experimental and theoretical investigation of explosive decomposition of ethylene
      oxide (EO) at fixed initial experimental parameters (T=100 degrees C, P=4 bar) in
      a 20-l sphere was conducted. Safety-related parameters, namely the maximum
      explosion pressure, the maximum rate of pressure rise, and the Kd values, were
      experimentally determined for pure ethylene oxide and ethylene oxide diluted with
      nitrogen. The influence of the ignition energy on the explosion parameters was
      also studied. All these dependencies are quantified in empirical formulas.
      Additionally, the effect of turbulence on explosive decomposition of ethylene
      oxide was investigated. In contrast to previous studies, it is found that
      turbulence significantly influences the explosion severity parameters, mostly the
      rate of pressure rise. Thermodynamic models are used to calculate the maximum
      explosion pressure of pure and of nitrogen-diluted ethylene oxide, at different
      initial temperatures. Soot formation was experimentally observed. Relation
      between the amounts of soot formed and the explosion pressure was experimentally
      observed and was calculated.

PMID- 15721526
TI  - Factors affecting the transformation of a pyritic tailing: scaled-up column
      tests.
AB  - Two different methods for predicting the quality of the water draining from a
      pyritic tailing are compared; for this, a static test (ABA test) and a kinetic
      test in large columns were chosen. The different results obtained in the two
      experimental set-ups show the necessity of being careful in selecting both the
      adequate predictive method and the conclusions and extrapolations derived from
      them. The tailing chosen for the weathering tests (previously tested in shake
      flasks and in small weathering columns) was a pyritic residue produced in a
      flotation plant of complex polymetallic sulphides (Huelva, Spain). The ABA test
      was a modification of the conventional ABA test reported in bibliography. The
      modification consisted in the soft conditions employed in the digestion phase.
      For column tests, two identical methacrylate columns (150 cm high and 15 cm
      diameter) were used to study the chemical and microbiological processes
      controlling the leaching of pyrite. The results obtained in the two tests were
      very different. The static test predicted a strong potential acidity for the
      tailing. On the contrary, pH value in the effluents draining from the columns
      reached values of only 5 units, being the concentration of metals (<600 mg/L) and
      sulphate ions (<17,000 mg/L) very small and far from the values of a typical acid
      mine drainage. In consequence, the static test may oversize the potential acidity
      of the tailing; whereas large columns may be saturated in water, displacing the
      oxygen and inhibiting the microbial activity necessary to catalyse mineral
      oxidation.

PMID- 15721527
TI  - Influence of the experimental conditions on porosity and structure of adsorbents
      elaborated from Moroccan oil shale of Timahdit by chemical activation.
AB  - This study records experiments undertaken to determine the suitable conditions
      for the use of the oil shale of Timahdit, as an adsorbent for water treatment. A
      simple process was proposed based on chemical activation. The preparation has
      been carried out by carbonization after impregnation of the precursor with
      phosphoric acid. The effect of different conditions of preparation on the
      specific surface area is discussed. These parameters are H3PO4/shale weight
      ratio, carbonization temperature, carbonization time and concentration of H3PO4.
      The properties and surface structure of the adsorbent were investigated by XPS
      and FT-IR. Their total surface acidity and basicity were also determined. The
      retention process of methylene blue (MB) by adsorbents has been studied. It was
      found that MHP2 and MHP7 have relatively high retention ability as compared to
      activated carbons.

PMID- 15721528
TI  - Revised estimates for continuous shoreline fumigation: a PDF approach.
AB  - A probability density function (PDF) fumigation model is presented here to study
      the dispersion of air pollutants emitted from a tall stack on the shoreline. This
      work considers dispersion of the pollutants in the stable layer and within the
      thermal internal boundary layer (TIBL) proceeds independently. The growth of TIBL
      is considered parabolic with distance inland. Turbulence is taken as homogeneous
      and stationary. Dispersion of particles (contaminant) in lateral and vertical
      directions is assumed independent of each other. This assumption allows us to
      consider the position of particles in both directions as independent random
      variables. The lateral dispersion distribution within the TIBL is considered as
      Gaussian and independent of height. A skewed bi-Gaussian vertical velocity PDF is
      used to account for the physics of dispersion due to different characteristics of
      updrafts and downdrafts within the TIBL. We have used Weil (J.C. Weil, A
      diagnosis of the asymmetry in top-down and bottom-up diffusion using a Lagrangian
      stochastic model, J. Atmos. Sci., 47 (1990) 501-515) solutions to find out the
      parameters of this PDF. Incorporating finite Lagrangian integral time scale for
      the vertical velocity component, it is observed that it reduces the vertical
      dispersion in the beginning and moves the point of maximum concentration further
      downwind. Due to little dispersion in the beginning, there is more plume to be
      dispersed causing higher concentrations at large distances. The model has
      considered Weil and Brower's (J.C. Weil, P.R. Brower, Estimating convective
      boundary layer parameters for diffusion applications, Maryland Power Plant Siting
      Program Rep. PPSP-MP-48, Department of Natural Resources, Annapolis, MD, 1985, 37
      pp.) convective limit to analyze dispersion characteristics within TIBL. The
      revised model discussed here is evaluated with the data available from the
      Nanticoke field experiment on fumigation conducted in summer of 1978 in Ontario,
      Canada. The results of revised model are in good agreement with the observed
      data.

PMID- 15721529
TI  - An ab initio study on ethylenedinitramine and its monovalent ions.
AB  - An explosive material, ethylenedinitramine (EDNA), its mono and di aci forms, as
      well as its monovalent cation and anion forms have been considered for 6-31G
      (UHF) type ab initio quantum chemical treatment in order to investigate the
      stability of EDNA in the neutral form and when charges develop on it exposed to
      electrical fields during the storage, handling or explosion process. The
      calculations indicate stable species. The aci forms are less stable than EDNA
      itself and the anion form is more stable than the neutral and cation forms.
      Although, the charge development is accompanied by some elongation or contraction
      of bonds and deviation of bond angles also as compared to the neutral state, no
      bond rapture occurs.

PMID- 15721530
TI  - Studies on energetic compounds Part 45. Synthesis and crystal structure of
      disodium azotetrazole pentahydrate.
AB  - A disodium salt of azotetrazolate (SAZ) has been prepared and characterized by
      elemental, UV, 13C NMR, FT-IR, and crystallographic analyses. Single crystals of
      the pentahydrate were grown by slow evaporation of an aqueous solution under
      reduced pressure. The crystal structure of SAZ has been determined by X-ray
      diffraction. The crystal lattice is triclinic P1 (no. 2) with lattice parameters
      a=7.115(1)A, b=7.559(1)A, c=12.025(1)A, alpha=79.75(1) degrees , beta=81.12(1)
      degrees , gamma=68.16(1) degrees and V=587.97(12)A3. Explosion delay studies have
      been undertaken using the tube furnace technique. The thermal stability of the
      compound has been discussed in the light of TG-DSC and explosion delay.

PMID- 15721531
TI  - Use of clay mineral (montmorillonite) for reducing poultry litter leachate
      toxicity (EC50).
AB  - Poultry litter (PL) has useful nutrients and is therefore used as manure. In
      addition to N, P and K, PL also contains some heavy metals (As, Cd, Cu, Mn, Pb
      and Zn), antibiotics, antioxidants, mold inhibitors and other organic compounds.
      Poultry litter aqueous leachate (PLL) has been shown to be toxic to many
      organisms; PLL is more toxic than the aqueous leachate of other animal manures
      used on agricultural soils. Clayey soils are known to retain toxic heavy metals.
      The objective of this study was to measure the change in toxicity (EC50) of PLL
      on the addition of clay mineral--montmorillonite. A significant reduction (124%)
      in toxicity of the clay poultry litter leachate (CLL) after 7 days was observed
      compared to the toxicity of the PLL alone after 1 day. This indicates that some
      of the toxic components of the litter were adsorbed by the clay.

PMID- 15721532
TI  - Comparison treatment of various chlorophenols by electro-Fenton method:
      relationship between chlorine content and degradation.
AB  - This study describes a comparative degradation of various chlorophenols by
      electro-Fenton method. Chloride released and reaction intermediate products were
      determined by ionic chromatography (IC) and gas chromatography/mass spectrometry
      (GC/MS). Using pentachlorophenol (PCP) as the model compound, we investigated the
      effects of cell voltage, electrolyte concentration and pH to optimize the
      degradation conditions. It was noted that the addition of small quantities of
      Fe3+ or Fe2+ significantly accelerated the degradation rate. Under the optimal
      conditions, electro-Fenton method was used to treat various chlorophenols
      including PCP, 4-chlorophenol (4-CP), 2,4-dichlorophenol (2,4-DCP), 2,4,6
      trichlorophenol (2,4,6-TCP) and their mixture aqueous solutions. Their pseudo
      first-order degradation rate constants at the first stages were calculated and
      compared, which gave the following sequence: 2,4-DCP>2,4,6-TCP>PCP>4-CP. The
      relationship between the chlorine content and degradation rate was discussed and
      compared with other advanced oxidation processes. Finally, we proposed the
      degradation pathways of different chlorophenols.

PMID- 15721533
TI  - Enhanced electrokinetic extraction of heavy metals from soils assisted by ion
      exchange membranes.
AB  - The potential of electrokinetic remediation technology has been successfully
      demonstrated for the remediation of heavy metal contaminated fine-grained soils
      through laboratory scale and field application studies. Various enhancement
      techniques have been proposed and used in order to further improve the
      remediation process. However, it has been reported that such enhancement schemes
      can create other obstacles, such as the introduction of non-target ions into the
      system and thereby decrease the efficiency of the remediation process.
      Electrokinetic soil remediation technology enhanced by an ion exchange membrane
      (IEM), IEM-enhanced EK processing, was experimentally evaluated for the purpose
      of overcoming these obstacles. In particular, this study focused on observations
      of a fouling problem and its settlement using an auxiliary solution cell (ASC).
      In addition, the efficacies of two different types of electrode configurations,
      rectangular and cylindrical, were investigated. The experimental results indicate
      that the effectiveness of the technology was increased by an enhancement scheme
      using an IEM. This may be explained by the prevention of metal precipitation in
      the region near the cathode originating from hydroxide ions generated by the
      electrolysis of water in the cathode. The experimental results also imply that
      placement of the ASC can nullify the fouling problem within the cation exchange
      membranes used in IEM-enhanced EK processing, and thus improve the overall
      effectiveness of the process. The experimental results indicate that the
      cylindrical electrode configuration can be implemented in practical situations to
      improve the treatability of cathode effluent containing a high level of
      contaminants after processing.

PMID- 15721534
TI  - Reactivity of Fe(II)/cement systems in dechlorinating chlorinated ethylenes.
AB  - Ferrous iron (Fe(II)) in combination with Portland cement is effective in
      reductively dechlorinating chlorinated organics and can be used to achieve
      immobilization and degradation of contaminants simultaneously. Reactivities of
      chlorinated ethylenes (perchloroethylene (PCE), trichloroethylene (TCE), 1,1
      dichloroethylene (1,1-DCE), vinyl chloride (VC)) in Fe(II)/cement systems were
      characterized using batch slurry reactors. Reduction kinetics of the chlorinated
      ethylenes were sufficiently fast to be utilized for the proposed treatment
      scheme, and were described by a pseudo-first-order rate law. The order of
      reactivity of the chlorinated ethylenes was TCE>1,1-DCE>PCE>VC. Reduction of TCE
      and PCE mainly yielded acetylene, implying that the transformation of the two
      compounds occurred principally via reductive beta-elimination pathways.
      Transformation of 1,1-DCE and VC gave rise to primarily ethylene, implying that
      major degradation pathways were a reductive alpha-elimination for the former and
      a hydrogenolysis for the latter. The reactivity of the Fe(II)/cement systems in
      dechlorinating TCE was proportional to Fe(II) dose when the Fe(II)/cement mass
      ratio varied between 5.6 and 22.3%. The Fe(II)/cement systems with a higher
      Fe(II) loading were less extensively affected by pH in reductive reactions for
      TCE than in the previous experiments with PCE or chlorinated methanes. Amendment
      of Fe(II)/cement systems with Fe(III) addition was found effective in increasing
      the reactivity in the previous study, but the current findings indicated that the
      extent to which the reaction rate increased by the amendment might be dependent
      on the source of the cement and/or the compounds tested.

PMID- 15721535
TI  - Bioremediation of chromium contaminated soil: optimization of operating
      parameters under laboratory conditions.
AB  - Bacterial strains were isolated and enriched from the contaminated site of Tamil
      Nadu Chromates and Chemicals Limited (TCCL) premises, Ranipet, Tamil Nadu, India.
      The strain which was isolated from the highly contaminated location had shown
      high Cr(VI) reduction potential. Cr(VI) reduction was evaluated both in aerobic
      and anaerobic conditions. Though the aerobic system performed better than the
      anaerobic one, further study were carried out in the anaerobic condition due to
      its economic viability. At higher initial concentration, Cr(VI) reduction was not
      complete even after 108 h, however, specific Cr(VI) reduction, unit weight of Cr
      reduced/unit weight of biomass was greater at higher concentration. It was found
      that a bacterial concentration of 15+/-1.0 mg/g of soil (wet weight) 50 mg of
      molasses/g of soil as carbon source were required for the maximum Cr(VI)
      reduction. The bioreactor operated at these conditions could reduce entire Cr(VI)
      (5.6 mg Cr(VI)/g of soil) in 20 days. The Cr(III) thus formed was found to be
      strongly attached to the soil matrix and the mobility of Cr(III) was negligible
      as evident from the low concentration of Cr(III) in the leachate. This study
      showed that bioremediation is a viable, environmental friendly technology for
      cleaning-up the chromium contaminated site at TCCL, Ranipet, Tamil Nadu, India,
      and optimal operating conditions under laboratory conditions were evaluated.

PMID- 15721536
TI  - Application of the electrokinetic-Fenton process for the remediation of kaolinite
      contaminated with phenanthrene.
AB  - This study explored the feasibility of applying the electrokinetic-Fenton process
      (EK-Fenton process) for the remediation of contaminant sorbed onto soil
      possessing low-permeability. The relationship of H2O2 stability and phenanthrene
      treatment, and the variation in the monitoring values were also investigated
      during the EK-Fenton process when catalyzed by heterogeneous minerals.
      Phenanthrene was chosen to represent hydrophobic organic contaminants (HOCs),
      which are widespread in the environment, and kaolinite was used as the low
      permeability soil. In these experiments, the H2O2 concentrations in pore water,
      the electrical potential distributions and the electrical currents were measured
      or monitored to assess the electrochemical effect in relation to injections of
      H2O2 from the anode. The results suggested that intermediate anions (HO2-, O2-)
      with Fenton-like reaction affected significantly the variations in the electrical
      current during the EK-Fenton process. The addition of 0.01 N H2SO4 to the anode
      reservoir improved the H2O2 stability and the treatment of phenanthrene in the
      entire soil specimen. Therefore, use of H2O2 and dilute acid, as an anode purging
      solution is a possible method for treating HOCs in low-permeability subsurface
      environments.

PMID- 15721537
TI  - Removal and preconcentration of inorganic and methyl mercury from aqueous media
      using a sorbent prepared from the plant Coriandrum sativum.
AB  - A sorbent prepared from the plant Coriandrum sativum, commonly known as coriander
      or Chinese parsley, was observed to remove inorganic (Hg2+) and methyl mercury
      (CH3Hg+) from aqueous solutions with good efficiency. Batch experiments were
      carried out to determine the pH dependency in the range 1-10 and the time
      profiles of sorption for both the species. Removal of both the forms of mercury
      from spiked ground water samples was found to be efficient and not influenced by
      other ions. Column experiments with silica-immobilized coriander demonstrated
      that the sorbent is capable of removing considerable amounts of both forms of
      mercury from water. The sorption behaviour indicates the major role of carboxylic
      acid groups in binding the mercury. The studies suggest that the sorbent can be
      used for the decontamination of inorganic and methyl mercury from contaminated
      waters.

PMID- 15721538
TI  - Rate studies on the adsorption of some dyestuffs and p-nitrophenol by chitosan
      and monocarboxymethylated(mcm)-chitosan from aqueous solution.
AB  - In this study, the effect of temperature on the adsorption of some dyestuffs
      [orange II (O-II), crystal violet (CV) and reactive blue 5 (RB5)] and p
      nitrophenol (PNP) by chitosan and of O-II and CV by modified chitosan
      [monocarboxymethylated(mcm)-chitosan] from aqueous solution was investigated.
      Kinetical data related to the adsorptions of each dyestuff and PNP by chitosan
      and of O-II and CV by mcm-chitosan were applied to Lagergren and Weber-Morris
      equations, and adsorption rate constants (kads) and pore diffusion rate constants
      (kp) were determined, respectively. In addition, Langmuir isotherm constants with
      experimental data related to the adsorptions of O-II and CV by chitosan and of CV
      by mcm-chitosan were applied to McKay et al. equation, and external mass transfer
      coefficients (kf) were also determined. Lastly, chitosan and mcm-chitosan were
      compared according to their dyestuffs and PNP uptake capabilities. It was seen
      that mcm-chitosan removed more O-II (99.2%) and RB5 (34.9%) but less CV (3.1%)
      and PNP (0.9%).

PMID- 15721539
TI  - Photooxidative degradation of Acid Red 27 in a tubular continuous-flow
      photoreactor: influence of operational parameters and mineralization products.
AB  - The decolorization and mineralization of Acid Red 27 (AR27), an anionic monoazo
      dye of acid class, was investigated using UV radiation in the presence of H2O2 in
      a tubular continuous-flow photoreactor as a function of oxidant concentration,
      reactor length, flow rate and light intensity. The removal efficiency of AR27
      depends on the operational parameters and increases as the initial concentration
      of H2O2 and light intensity are increased but it decreases when the flow rate is
      increased. The AR27 degradation was followed through HPLC, UV-vis and COD
      analyses. The results of these analyses showed that the final outlet stream from
      the photoreactor was completely mineralized. The UV/H2O2 process was also able to
      mineralize nitrogen and sulfur heteroatoms into NH4+, NO3-, NO2- and SO4(2-)
      ions, respectively. The nitrogen of azo group was transformed predominantly to
      NH4+ ions. Decreasing the flow rate results in the reduction of COD and promotion
      of SO4(2-) at the final outlet stream of the photoreactor.

PMID- 15721540
TI  - Influence of soil components on adsorption-desorption of hazardous organics
      development of low cost technology for reclamation of hazardous waste dumpsites.
AB  - The waste disposal practices on land frequently lead to the deposition of
      hazardous waste at geologically/hydrogeologically unsuitable locations, resulting
      in surface and groundwater contamination. The movement of chemicals through soil
      is not only dependent on the physical, chemical and biological properties of the
      waste but also on the characteristics of the soil of the disposal site. In this
      paper the authors report their results on the influence of soil components on
      adsorption-desorption of certain industrially widely used hazardous organics like
      phenol, p-nitrophenol, 4-chloro-2-nitrophenol and 2,4-dichlorophenol on typical
      soils of Patancheru industrial area (Hyderabad, AP, India). The data on nature of
      organics, soil organic matters, clay, free iron and aluminum oxides of soils are
      known to influence the adsorption-desorption process are presented. There was
      reduction up to 67.5% (organic matter removed), 53.8% (clay removed) and 24.2%
      (iron and aluminum oxides removed) in the adsorption capacity of the soils when
      compared to untreated soils indicating the role played by these soil components
      in adsorption process. Desorption isotherms of soil adsorbed hazardous organics
      exhibited hysteresis at higher initial concentration indicating the degree of
      irreversibility of adsorption-desorption process. Mixed microbial cultures were
      developed which can degrade the hazardous organics to complete mineralisation by
      utilizing them as sole source of carbon and their corresponding biokinetic
      constants were evaluated. Preparation of dumpsites with suitable soil surface
      having high holding capacity for organics and their in situ biodegradation by
      mixing with specific microbial cultures can be exploited as a cost effective
      technology for reclamation of hazardous waste dumpsites.

PMID- 15721541
TI  - Application of a new electrolyte circulation method for the ex situ
      electrokinetic bioremediation of a laboratory-prepared pentadecane contaminated
      kaolinite.
AB  - Ex situ electrokinetic (EK) bioremediation of a laboratory-prepared pentadecane
      contaminated kaolinite was carried out. Extraneous bacteria and ionic nutrients
      were continuously supplied to the soil specimen by a new electrolyte circulation
      method, which controlled electrical pH change of electrolyte solution to keep
      bacterial activity. During the EK bioremediation the anode region showed the
      highest colony forming unit (CFU) due to electrical attraction between anode and
      bacteria. Simultaneous increases of CFU and uniform pentadecane removal in most
      soil regions demonstrated that electro-osmosis as well as electrophoresis
      affected the bacterial transport in soil. At 3.13 mA/cm2, increase in soil
      temperature to above 45 degrees C inhibited bacterial activity, which caused the
      decrease of removal efficiency. The removal amount of pentadecane increased with
      initial pentadecane concentration at the same current densities (0.63 and 1.88
      mA/cm2) because of the increased amount of weakly bound pentadecane onto the soil
      surface. The highest removal efficiency (77.6%) was obtained at 0.63 mA/cm2 for
      1000 mg/kg pentadecane after 14 days. Consequently, the present methods of EK
      bioremediation demonstrated superiority over the conventional bioremediation,
      which had inherent demerits of slow degradation and low removal efficiency.

PMID- 15721542
TI  - Decomposition of 2-naphthalenesulfonate in electroplating solution by ozonation
      with UV radiation.
AB  - This study investigates the ozonation of 2-naphthalenesulfonate (2-NS) combined
      with UV radiation in the electroplating solution. 2-NS is commonly used as a
      brightening and stabilization agent in the electroplating solution. Semibatch
      ozonation experiments were conducted under various reaction conditions to study
      the effects of ozone dosage and UV radiation on the oxidation of 2-NS. The
      concentrations of 2-NS were analyzed at specified time intervals to elucidate the
      decomposition of 2-NS. Total organic carbon (TOC) is chosen as a mineralization
      index of the ozonation of 2-NS. In addition, values of pH and oxidation reduction
      potential were continuously measured in the course of experiments. As a result,
      the nearly complete mineralization of 2-NS via the ozonation treatment can be
      achieved. The mineralization of 2-NS is found accelerated by the introduction of
      UV radiation and has a distinct relationship with the consumption of applied
      ozone. These results can provide useful information for the proper removal of 2
      NS in the electroplating solution by the ozonation with UV radiation.

PMID- 15721543
TI  - A SEM and X-ray study for investigation of solidified/stabilized arsenic-iron
      hydroxide sludge.
AB  - Despite the fact that the solidification/stabilization of arsenic containing
      wastes with Portland cement and lime has an extensively documented history of
      use, the physical and chemical phenomena as a result of the interaction between
      arsenic and cement components have not been fully characterized. The study
      investigates the behavior of synthesized arsenic-iron hydroxide sludge, the by
      product of arsenic removal by coagulation with ferric chloride, in
      solidified/stabilized matrices as well as its binding mechanisms by exploring the
      cementitious matrices in the micro-scale by scanning electron microscopy equipped
      with energy dispersive X-ray spectrometer (SEM-EDS). It was revealed that arsenic
      can be chemically fixed into cementitious environment of the
      solidified/stabilized matrices by three important immobilization mechanisms;
      sorption onto C-S-H surface, replacing SO4(2-) of ettringite, and reaction with
      cement components to form calcium-arsenic compounds, the solubility limiting
      phases.

PMID- 15721544
TI  - Electrochemical-assisted photodegradation of dye on TiO2 thin films:
      investigation on the effect of operational parameters.
AB  - Electrochemical-assisted photodegradation of methyl orange has been investigated
      using TiO2 thin films. The films were prepared by sol-gel dip-coating method.
      Several operational parameters to achieve optimum efficiency of this
      electrochemical-assisted photodegradation system have been tested.
      Photoelectrochemical degradation was studied using different light sources and
      light intensity. The light sources chosen ranged from ultraviolet to visible
      light. The effect of agitation of the solution at different speeds has also been
      studied. Slight improvement of photodegradation rate was observed by applying
      higher agitation speed. Investigation on the electrode after repeated usages show
      the electrode can be reused up to 20 times with percentage of deficiency less
      than 15%. The study on the effect of solution temperature indicated that the
      activation energy of the methyl orange degradation is 18.63 kJ mol(-1).

PMID- 15721545
TI  - Effects of gap size and UV dosage on decolorization of C.I. Acid Blue 113
      wastewater in the UV/H2O2 process.
AB  - The wastewater from textile dyeing industry is difficult to be treated
      successfully according to both high variability of composition and color
      intensity. To investigate the effects of reactor gap size and UV dosage on the
      decolorization of dye wastewater, a commercially available azo dye C.I. Acid Blue
      113 was chosen as a model compound. UV/H2O2 processes with various gap sizes and
      setups of plug flow reactor and recirculated batch reactor were proposed to deal
      with the dye wastewater in this study. The experimental parameters including the
      design of reactor configurations of annular gap size, and in batch system or plug
      flow reactors and hydrogen peroxide dosage, UV dosage were investigated. The gap
      size of reactor was adjusted by different diameter of reactor shells in order to
      optimize the reactor configuration. The color removal percentage was used to
      evaluate the treatment efficiency. An optimal hydrogen peroxide concentration of
      46.53 mM was observed in this study for highest decolorization rate. Besides, the
      pseudo-first-order rate constant of 3.14 min(-1) was obtained by plug flow
      reactor with 0.5 cm gap size, 120.70 W/l of UV dosage and 23.27 mM of H2O2
      dosage. The first-order rate constant, which was about 20 times less than that of
      plug flow reactor, was obtained 0.1422 min(-1) by recirculated batch reactor with
      2.0 cm gap size, 7.0 W/l of UV and 23.27 mM of H2O2 dosages. Ultimately, we
      developed an effective pre-treatment or treatment technology for dye wastewater
      to provide the dyeing industries and dye manufacturers an alternative to meet the
      effluent standards.

PMID- 15721546
TI  - Flocculation behaviour of model textile wastewater treated with a food grade
      polysaccharide.
AB  - In this study, the application of a food grade polysaccharide namely Plantago
      psyllium mucilage has been assessed for the removal of dyes from model textile
      wastewater containing golden yellow (C.I. Vat Yellow 4) and reactive black (C.I.
      Reactive Black 5). A series of contact time experiments were conducted to assess
      the system variables such as concentrations of mucilage and dyes and pH. This
      mucilage reduces the dye concentration by flocculation and settling. The optimal
      flocculant concentration required to affect flocculation is independent of dye
      concentration within the range examined. The dye removal obtained was influenced
      by the salts concentrations in the wastewater sample. The flocculation efficiency
      was sensitive to pH when pure aqueous solutions of dyes were used, but it was
      relatively unaffected by pH change when salts were added to the dye solutions.
      The experimental results show that the mucilage is more effective for removal of
      solubilised vat dye than for reactive black.

PMID- 15721547
TI  - Study on the photocatalysis performance and degradation kinetics of X-3B over
      modified titanium dioxide.
AB  - In this paper, reactive brilliant X-3B was used as a model compound to study the
      photocatalytic activity of TiO2. Experimental results showed that the
      adulteration of iron and silver on TiO2 could greatly improve the activity of
      TiO2, and the optimum adulteration amount of iron and silver was 0.1 wt.%
      (Fe/TiO2) and 0.05 wt.% (Ag/TiO2), respectively, at the adulteration range of
      experiments. The photocatalytic degradation kinetics of X-3B on TiO2, Fe/TiO2 and
      Ag/TiO2 were also studied. The results showed that the degradation of X-3B on all
      of them were in accordance with the Langmiur-Hinshelwood kinetics model well, and
      the sequence of apparent reaction rate constants k of X-3B degradation catalyzed
      by TiO2, Fe/TiO2 and Ag/TiO2 was Ag/TiO2>Fe/TiO2>TiO2, while adsorption
      equilibrium constants KA of X-3B on Fe/TiO2 and Ag/TiO2 were approximately the
      same, and both were greater than that of TiO2.

PMID- 15721548
TI  - Model applications and mechanism study on the degradation of atrazine by Fenton's
      system.
AB  - Atrazine (ATZ), 2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine, was
      effectively degraded by hydroxyl radicals that were generated by FeII/H2O2 in the
      Fenton's process. Up to 98% ATZ removal can be achieved in the process if the
      doses of FeII and H2O2 are selected appropriately. Oxidation capacity of the
      process was successfully predicted through a kinetic approach with three simple
      and measurable parameters (i.e., two rate constants and a break point time),
      which makes the model useful in predicting, controlling and optimizing the
      degradation of ATZ. In addition, the transformation pathways of ATZ decay was
      successfully investigated by using a novel technology, liquid chromatography
      electrospray tandem mass spectrometry (LC/ESI-MS/MS). Ten intermediates were
      identified in the process. The alkylic-oxidation followed by dealkylation and/or
      dechlorination-hydroxylation were found to be the major pathways of the decay of
      ATZ in Fenton's process. All the detected intermediates were found to be
      dealkylated in different levels or positions. The dealkylated species may be
      further dechlorinated but generally at a lower fraction (<10%) due to the
      depletion of oxidants.

PMID- 15721549
TI  - Modeling of chlorophenols competitive adsorption on soils by means of the ideal
      adsorbed solution theory.
AB  - The adsorption of 3-chlorophenol (3-CP) and 3,5-dichlorophenol (3,5-CP) on two
      Italian soils was studied at 20 degrees C. Experiments on the pure components
      showed that 3,5-CP was more strongly adsorbed than 3-CP, and that the adsorption
      capacity could be related to the organic carbon fraction of the soil. Competitive
      adsorption data were described by the fully predictive ideal adsorbed solution
      (IAS) theory. To this end, the Langmuir parameters determined from pure component
      adsorption data were used. Results showed that at low 3,5-CP concentration (up to
      5-10 mM) the model describes satisfactorily the binary system behavior, whereas
      at higher concentrations predictions fail, suggesting that non ideality effects
      in the adsorbed phase should be accounted for.

PMID- 15721550
TI  - Biodegradation of fenoxaprop-p-ethyl by bacteria isolated from sludge.
AB  - A mixed bacterial population was isolated using enrichment in a basal medium
      containing increasing amounts of fenoxaprop-p-ethyl as a sole carbon source from
      sludge that had been exposed to fenoxaprop-p-ethyl production wastewater for
      about 2 years. Eight kinds of isolates could utilize fenoxaprop-p-ethyl, but only
      one was identified belonging to genus Alcaligenes, named Alcaligenes sp. H. In
      pure culture, there was 45.8, 66.0 and 69.5% loss of fenoxaprop-p-ethyl (initial
      concentration: 100, 50, 25 ppm, respectively) as the sole carbon source with
      biodegradation by Alcaligenes sp. H and fenoxaprop-p-ethyl degradation kinetics
      obeyed the first-order kinetics, the same as the fenoxaprop-p-ethyl
      biodegradation kinetics in soil. At least five degradation products of fenoxaprop
      p-ethyl biodegradation by Alcaligenes sp. H and two degradation products of
      fenoxaprop-p-ethyl biodegradation by Huv separated by HPTLC. It is possible that
      the fenoxaprop-p-ethyl biodegradation by Alcaligenes sp. H includes the same
      pathway as that by Huv comparing with the Rf.

PMID- 15721551
TI  - Comment on "nitrate removal from aqueous solution by adsorption onto various
      materials" by N. Ozturk, T.E. Bektas.
AB  - A research paper's contribution exists not only in its originality and creativity
      but also in its continuity and development for research that follows. The
      reference section can play a key role to researchers who are interested in a
      paper's statement or who would like to follow the study or find useful
      information from the paper. Citation error and quotation error occurred very
      frequently in a scientific paper, however, the author easily ignores it. Ozturk
      and Bektas published a paper, there is no doubt about this paper, which was
      previously evaluated and accepted for publication. This study presents quotation
      and citation errors of Lagergren's pseudo-first order rate equation and Ho's
      pseudo-second order rate expression. It is also suggested that an author not only
      must be creative but also must be careful while writing in order to publish more
      valuable and papers more worthy of reading.

PMID- 15721552
TI  - Effect of fatty oil dispersion on oil-containing wastewater treatment.
AB  - The performance of an immobilized continuous fluidized reactor for salad oil
      containing model wastewater was examined at a high loading rate using
      polyurethane as a support, to be applied in fat- and oil-containing wastewater
      treatment, generated by daily activities in restaurant kitchens. At an organic
      loading rate higher than 0.6 kg/m3/day, there was a significant amount of white
      solid (WS), identified as a mixture of calcium di-stearate and di-palmitate,
      suggesting that saturated fatty acid degradation was limited at such a high
      loading rate, possibly due to its solubility in the wastewater. Increased oil
      dispersion by the addition of a surfactant ranging from 10 to 100 microm particle
      size could result in less than 30 mg/l oil concentration after the treatment at 5
      kg/m3/day.

PMID- 15721553
TI  - Production of activated carbon from a new precursor molasses by activation with
      sulphuric acid.
AB  - Activated carbon has been prepared from molasses, a natural precursor of
      vegetable origin resulting from the sugar industry in Morocco. The preparation of
      the activated carbon from the molasses has been carried out by impregnation of
      the precursor with sulphuric acid, followed by carbonisation at varying
      conditions (temperature and gas coverage) in order to optimize preparation
      parameters. The influence of activation conditions was investigated by
      determination of adsorption capacity of methylene blue and iodine, the BET
      surface area, and the pore volume of the activated carbon were determined while
      the micropore volume was determined by the Dubinin-Radushkevich (DR) equation.
      The activated materials are mainly microporous and reveal the type I isotherm of
      the Brunauer classification for nitrogen adsorption. The activated carbons
      properties in this study were found for activation of the mixture
      (molasses/sulphuric acid) in steam at 750 degrees C. The samples obtained in this
      condition were highly microporous, with high surface area (> or =1200 m2/g) and
      the maximum adsorption capacity of methylene blue and iodine were 435 and 1430
      mg/g, respectively.

PMID- 15721554
TI  - Reply to comment of Dr. Ho on "J. Hazard. Mater. 108 (2004) 183-188".

PMID- 15721555
TI  - Argon protects hypoxia-, cisplatin- and gentamycin-exposed hair cells in the
      newborn rat's organ of Corti.
AB  - During the last few years, an important protective effect of the noble gas xenon
      against neuronal hypoxic damage was observed. However, argon (Ar), a gas from the
      same chemical group, but less expensive and without anesthetic effect at
      normobaric pressure, has not been studied in terms of possible biological effects
      on cell protection. Ar was tested for its ability to protect organotypic cultures
      of the organ of Corti from 3-5 day old rats against hypoxia, cisplatin, and
      gentamycin toxicity. Cultures were exposed to nitrogen hypoxia (5% CO2, 95% N2),
      Ar hypoxia (5% CO2, 95% Ar) or normoxia for 30 h. Ar protected the hair cells
      from hypoxia-induced damage by about 25%. Ar-oxygen (O2) mixtures (21% O2, 5%
      CO2, 74% Ar) had no effect on the hair cell survival. Cisplatin (7.5-25 microM)
      and gentamycin (5-40 microM) exposed in medium under air damaged the hair cells
      in a dose-dependent manner. The exposure of cisplatin- and gentamycin-treated
      cultures to the Ar-O2 atmosphere significantly reduced the hair cell damage by up
      to 25%. This protective effect of Ar might provide a new protective approach
      against ototoxic processes.

PMID- 15721556
TI  - Relationship between auditory perception skills and mismatch negativity recorded
      in free field in cochlear-implant users.
AB  - This study investigated the ability of cochlear-implanted patients to
      discriminate tone bursts in free field using the electrophysiological recordings
      of mismatch negativity (MMN). Seven cochlear-implanted patients (CIP) and eight
      control subjects (CS) were tested. Event-related potentials were recorded from
      either 32 or 64 electrodes in response to binaural stimuli using a passive
      oddball paradigm. Two stimulus-contrast conditions were used to produce MMN: The
      standard-tone frequency was fixed at 1 kHz, and the deviant-tone frequency was
      set at 2 or 1.5 kHz. The results show that response waveforms (N1/P2) are similar
      in latency and amplitude for CS and CIP, suggesting that pure-tone detection is
      performed over the same time window in both groups. These waveforms are also
      similar in left- and right-implanted patients, suggesting that electric
      stimulation of the auditory nerve activates both hemispheres in profound,
      bilateral hearing loss. Pure-tone audiograms and word-discrimination scores were
      also measured in each subject in an anechoic room and their relations with MMN
      data were examined. Correlations were found between the latency of MMN for a 1.5
      kHz deviant and the thresholds obtained for pure-tone detection and word
      discrimination. MMN appears as a possible complementary clinical tool to
      objectively assess auditory sensitivity in cochlear-implanted populations.
      However, further improvements are still necessary before it can be used as a
      standard clinical examination.

PMID- 15721557
TI  - Expression of the integrin genes in the developing cochlea of rats.
AB  - Integrins play an important role in the development of the cochlea. However,
      little is known about the expression pattern of integrins in the developing
      cochlear tissue. In this study, we investigated the dynamic expression profile of
      the integrin genes in the developing cochlear tissue of rats by Affymetrix
      microarrays and explored the role of the integrin genes in vitro by using
      antisense oligonucleotides. It was demonstrated that the alpha1, alpha7, alphav,
      beta3, and beta4 genes were expressed in the developing cochlear tissue of rats.
      Inhibition of the integrin expression with antisense oligonucleotides against
      alphav, alpha7, beta3, and beta4, respectively, in cochlear sensorineural
      epithelial cells significantly decreased the [3H]thymidine incorporation,
      suggesting that these integrins are involved in cell growth and proliferation.
      Inhibition of the alphav and beta4 integrins significantly decreased the
      transcription of nuclear factor-kappa B (NF-kappaB, a signal molecule involved in
      cell growth and proliferation) induced by epidermal growth factor (EGF) and basic
      fibroblast growth factor (bFGF), respectively. It suggests that EGF-induced cell
      growth is dependent upon the alphav integrin whereas bFGF-induced cell growth is
      dependent upon the beta4 integrin in the cochlear tissue during the development
      of the inner ear.

PMID- 15721558
TI  - Effects of noise exposure on click detection and the temporal resolution ability
      of the goldfish auditory system.
AB  - Hearing specialist fishes investigated so far revealed excellent temporal
      resolution abilities, enabling them to accurately process temporal patterns of
      sounds. Because noise is a growing environmental problem, we investigated how it
      affects the temporal resolution ability of goldfish. Auditory evoked potentials
      (AEPs) in response to clicks and double clicks were recorded before exposing,
      immediately after exposing the fish to white noise of 158 dB re 1 microPa for 24
      h, and after 3, 7 and 14 days of recovery. Immediately after noise exposure,
      hearing sensitivity to clicks was reduced on average by 21 dB and recovered
      within 1 week. Amplitudes of the AEPs decreased by about 71% while latencies
      increased by 0.63 ms. Both AEP characteristics returned to baseline values within
      2 weeks. Analysis of the response to double clicks showed that the minimum click
      period resolvable by the auditory system increased significantly from 1.25 to
      2.08 ms immediately after noise exposure. After a recovery period of 3 days, this
      minimum period returned to pre-exposure values. The present study revealed that
      noise exposure affects the detection of short transient signals and the temporal
      resolution ability. Because acoustic information is primarily encoded via
      temporal patterns of sounds in fishes, environmental noise could severely impair
      acoustic orientation and communication.

PMID- 15721559
TI  - The membranous labyrinth during larval development in lamprey (Lampetra planeri,
      Bloch, 1784).
AB  - SEM and CLSM studies were performed on the membranous labyrinth of Lampetra
      planeri, a threatened species of brook lamprey, spanning from the 1st to the 4th
      year of ammocoetes larval stages and on the adults. In all the examined stages,
      the entire membranous labyrinth does not show any morphologic differences, but
      only a progressive increase in size. SEM and CLSM observations show that the
      ciliated chamber is lined with numerous unsensorial multiciliated cells. In the
      early stages, the ciliary bundles were approximately 15 microm long, while in the
      late stages they reached 30 microm. In the crista sensory area, we observed two
      populations of hair cells. "Type II" cells are peculiar for this species and show
      both long stereocilia decreasing in length and a long kinocilium (10-12 microm).
      Two other types of ciliary bundles have been found on the sensory hair cells of
      the Macula communis: the first one has both kinocilium and stereocilia about 4-5
      microm long; the second shows a long kinocilium (7-10 microm in length) and short
      stereocilia bundles with a gradual increase in length. In the early stages of
      development, the three macular areas show few and sparsely distributed hair
      cells. In the late developmental stages, hair cells become more numerous and
      densely populated.

PMID- 15721560
TI  - Compression estimates using behavioral and otoacoustic emission measures.
AB  - Cochlear compression in normal-hearing listeners was estimated at octave
      frequencies from 250 to 4000 Hz using a forward-masking paradigm. Temporal
      masking curves (TMCs) for a 10-dB SL signal were obtained with two maskers -- one
      equal in frequency to the signal and another an octave below the signal. The
      ratio of the slope of the off-frequency function to that of the mid-level portion
      of the on-frequency function was computed as an estimate of the amount of
      compression at each frequency. Compression was less frequency selective at low
      frequencies, so an average of the off-frequency slopes at high frequencies (1000,
      2000, and 4000 Hz) was used in computing the ratio for each signal frequency.
      Results indicated strong compression (approximately 0.15-0.30) at all frequencies
      using the averaged off-frequency slopes, indicating little difference in
      compression across frequencies. Distortion product otoacoustic emission (DPOAE)
      input-output (I-O) functions were obtained for each subject at 1000, 2000, and
      4000 Hz. The slopes of the DPOAE I-O functions and the psychophysical growth
      rates were similar to one another, reinforcing the assumption that the forward
      masking procedure is providing an estimate of cochlear compression, at least at
      frequencies from 1000 to 4000 Hz.

PMID- 15721561
TI  - Fish otolith mass asymmetry: morphometry and influence on acoustic functionality.
AB  - The role of the fish otolith mass asymmetry in acoustic functionality is studied.
      The saccular, lagenar and utricular otoliths are weighted in two species of the
      Black Sea rays, 15 species of the Black Sea teleost fish and guppy fish. The
      dimensionless otolith mass asymmetry chi is calculated as ratio of the difference
      between masses of the right and left paired otoliths to average otolith mass. In
      the most fish studied the otolith mass asymmetry is within the range of -0.2 <
      chi < +0.2 (< 20%). We do not find specific fish species with extremely large or
      extremely small otolith asymmetry. The large otoliths do not belong solely to any
      particular side, left or right. The heavier otoliths of different otolithic
      organs can be located in different labyrinths. No relationship has been found
      between the magnitude of the otolith mass asymmetry and the length (mass, age) of
      the animal. The suggested fluctuation model of the otolith growth can interpret
      these results. The model supposes that the otolith growth rate varies slightly
      hither and thither during lifetime of the individual fish. Therefore, the sign of
      the relative otolith mass asymmetry can change several times in the process of
      the individual fish growth but within the range outlined above. Mathematical
      modeling shows that acoustic functionality (sensitivity, temporal processing,
      sound localization) of the fish can be disturbed by the otolith mass asymmetry.
      But this is valid only for the fish with largest otolith masses, characteristic
      of the bottom and littoral fish, and with highest otolith asymmetry. For most
      fish the values of otolith mass asymmetry is well below critical values. Thus,
      the most fish get around the troubles related to the otolith mass asymmetry. We
      suggest that a specific physicochemical mechanism of the paired otolith growth
      that maintains the otolith mass asymmetry at the lowest possible level should
      exist. However, the principle and details of this mechanism are still far from
      being understood.

PMID- 15721562
TI  - Excitability of auditory brainstem neurons, in vivo, is increased by cyclic-AMP.
AB  - Physiological control of auditory neural responses is critical for accurate
      representation of acoustic information, such as sound source localization and
      speech perception. Central auditory neural responses are almost certainly
      regulated by a range of mechanisms, including second messenger systems, such as
      the cAMP pathway. An increase in spontaneous neural discharge is known to
      accompany cochlear insults. Here we report that an increase in spontaneous as
      well as tone-evoked discharge can also be induced by pressure application of
      forskolin, a pharmacological agent that elevates intracellular cAMP level by
      activating adenyl cyclase. The forskolin induced increase in superior olivary
      complex (SOC) brainstem neurons is specific, dose-dependent, and reversible,
      whereas application of artificial cerebrospinal fluid (aCSF, the vehicle) does
      not alter activity. Forskolin-application also has a relatively greater effect on
      spontaneous activity compared to tone evoked responses. Blockade of the
      hyperpolarization-activated current, Ih, by ZD7288, consistently reversed the
      effects of forskolin. Based on these findings, we propose that the second
      messenger, cAMP, can significantly modulate neural excitability and spontaneous
      discharge in SOC neurons, principally by shifting the activation of Ih channels.

PMID- 15721563
TI  - Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral
      administration of allopurinol and ebselen.
AB  - Cisplatin ototoxicity has been associated with the generation of toxic levels of
      reactive oxygen species (ROS) which can lead to injury or loss of outer hair
      cells in the organ of Corti, damage to the stria vascularis, and loss of spiral
      ganglion cells, resulting in permanent hearing loss. In an attempt to reduce the
      formation of ROS and to bolster the innate oxidative stress defenses of the
      cochlea, we tested individual and combined formulations of allopurinol, a
      xanthine oxidase inhibitor, and ebselen, a glutathione peroxidase mimic. We used
      an acute cisplatin toxicity rat model (16 mg/kg i.p.) to analyze allopurinol and
      ebselen alone and in combination for their ability to reduce cisplatin associated
      hearing loss and nephrotoxicity. The results from our studies indicate that a
      combined formulation of ebselen and allopurinol affords significant protection to
      the cochlea and kidney from cisplatin toxicity. In the cochlea, protection is
      dependent on the preservation of outer hair cell number, while in the kidney,
      protection is associated with the preservation of proximal tubular epithelia.
      Further evaluation of the chemoprotective effects of ebselen and allopurinol on
      cisplatin side effects in the presence of tumor appears warranted.

PMID- 15721564
TI  - Frequency-specific cochlear damage in guinea pig after exposure to different
      types of realistic industrial noise.
AB  - For the causal evaluation of occupational hearing damage it is important to
      identify definitely the noise source. Here we tested, whether recordings of
      distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs can
      distinguish the effects of different industrial noises. Six groups of 12 animals
      each were investigated before and over four months after a single 2 h exposure to
      specific, played-back industrial noise as well as before and for 2 months after
      impulse noise exposure. We compared broadband noise (buzz saw, bottle washing
      machine), low frequency noise (drawing press), and mid-frequency noise (bottle
      filling machine). All animals had stable DPOAE levels before noise exposure.
      Frequency specific decreases in DPOAEs were found after exposure to the different
      noises. Broadband noise diminished mostly all frequencies tested, whereas low- or
      mid-frequency noise had a greater effect on DPOAE evoked by middle and higher
      frequencies, respectively. DPOAE evoked by middle and higher frequencies were
      obliterated after impulse noise. Morphological analysis of the cochleae confirmed
      these alterations. OHC loss was found in the middle turns of the cochleae
      corresponding to the diminution of DPOAE. We conclude that different kinds of
      industrial noise tend to produce typical changes in DPOAE levels.

PMID- 15721565
TI  - Efferent-mediated adaptation of the DPOAE as a predictor of aminoglycoside
      toxicity.
AB  - Rapid efferent adaptation of the distortion product otoacoustic emission (DPOAE)
      predicts susceptibility to noise-induced damage, and is linked to the
      concentration of the efferent receptor (alpha9). Maximum adaptation occurs at
      intense primary levels, rapidly switching from positive to negative orientation
      in a very narrow (2 dB) range of F1 and F2 levels. Aminoglycosides are commonly
      used antibiotics, with the undesirable side-effect of ototoxicity. Susceptibility
      to hair cell damage from the aminoglycoside gentamicin can be quite variable,
      even within a single strain and species of animal. Since one of gentamicin's
      first sites of action in the outer hair cell (OHC) is at the efferent receptor,
      it is possible that efferent activity could be a predictor of susceptibility to
      gentamicin induced damage. Significant sex-related differences were found in two
      strains of guinea pigs when treated with gentamicin. Female guinea pigs were more
      susceptible both to systemic effects and to specific ototoxic effects. Efferent
      mediated DPOAE adaptation served as a predictor of sensitivity to aminoglycoside
      damage, predicting both number of days before onset of deafness in male animals,
      and predicting final threshold shifts from gentamicin doses which produced
      variable results.

PMID- 15721566
TI  - Predicting severity of cochlear hair cell damage in adult chickens using DPOAE
      input-output functions.
AB  - Distortion product otoacoustic emissions (DPOAE) were recorded from the ear canal
      of aged broiler chickens which have been shown to present with age-related
      cochlear degeneration [Hear. Res. 166 (2002) 82]. We describe the relationship
      between the shape of the DPOAE input-output (I/O) function and the type of hair
      cell damage present at and between the cochlear frequency places of the DPOAE
      primary tones (f1 and f2). The mid stimulus level compressive growth of the mean
      DPOAE I/O functions is reduced in a graded fashion relative to the severity of
      hair cell damage. However, individual DPOAE I/O functions within most hair cell
      damage groups show large variability from this characteristic. Various least
      squares regression models were used to predict hair cell density from indices
      derived from the DPOAE I/O function (area, threshold and slope). The results
      showed that no simple linear relationship exists between hair cell density and
      the DPOAE I/O function indices. Multivariate binary logistic regression used
      DPOAE I/O function indices to predict membership in hair cell damage groups. The
      logistic model revealed that DPOAE threshold can be used to predict the
      occurrence of severe/total hair cell damage with good specificity though poor
      sensitivity.

PMID- 15721567
TI  - Cochlear structure and function after round window application of ototoxins.
AB  - Topical round window application of ototoxic agents has been a useful method for
      studying ototoxicity and hearing loss in the mammalian cochlea. For example,
      species-specific differences in cochlear susceptibility to damage have been
      documented using this technique. Carboplatin has been characterized in the
      literature as a selective inner hair cell (IHC) toxin in chinchillas, while
      cisplatin has been characterized as a selective outer hair cell (OHC) toxin. The
      present experiment quantified dose-dependent damage to cochlear hair cells in the
      chinchilla after a single direct round window application of either cisplatin or
      carboplatin. Detailed cytocochleograms were obtained for the entire cochlear
      duct, for a range of doses, along with auditory brainstem response thresholds. In
      agreement with the literature, although there was variability, at the lowest
      concentrations tested (2 and 3 mg/ml), carboplatin produced substantial IHC
      damage with no OHC damage. In contrast, the effects of cisplatin were more
      variable, and contrary to published reports, across the range of doses producing
      OHC damage, IHC damage was always observed. Limitations of direct round window
      ototoxin treatments are discussed, in addition to their potential application in
      the study of tinnitus.

PMID- 15721568
TI  - Changes in transient receptor potential cation channel superfamily V (TRPV) mRNA
      expression in the mouse inner ear ganglia after kanamycin challenge.
AB  - The transient receptor potential cation channel subfamily V (TRPV) is a non
      specific cation ion channel receptor family that is gated by heat, protons, low
      extracellular osmolarity and arachidonic acid derivatives. Since some of these
      endogenous agonists of TRPV receptors are reactive oxygen intermediates produced
      by lipoxygenases, it has been hypothesized that some members of the TRPV family
      may respond to challenges by reactive oxygen species. This study used real-time
      PCR to quantitatively track changes in TRPV1-4 mRNA expression in the spiral,
      vestibular, and trigeminal ganglia and the kidney from kanamycin (KM)-treated
      mice. TRPV1, TRPV2, TRPV3 and TRPV4 mRNAs were expressed in spiral and vestibular
      ganglia, and TRPV2 and TRPV1 mRNAs were most predominant in control mice. After
      KM (700 mg/kg s.c. b.i.d., 14 days), TRPV1 mRNA and protein expression were
      significantly up-regulated both in the spiral and vestibular ganglia, but
      expression was unaffected in the trigeminal ganglion and kidney. Real-time PCR
      also demonstrated a significant down-regulation in TRPV4 mRNA expression in the
      inner ear ganglia and kidney after KM treatment. All these mRNA and protein
      expression changes were eliminated by simultaneous administration of
      dihydroxybenzoate (300 mg/kg s.c. b.i.d., 14 days), an anti-oxidant that blocks
      KM ototoxicity. It is proposed that up-regulated TRPV1 expression during KM
      exposure may promote ganglion cell survival by contributing to neuronal
      depolarization, with KM-induced tinnitus and dizziness as consequences.

PMID- 15721569
TI  - Disrupted tonotopy of the auditory cortex in mice lacking M1 muscarinic
      acetylcholine receptor.
AB  - Sensory cortices have multiple and distinct functional maps that systematically
      represent environmental information. Development of these maps is precisely
      controlled by a number of intrinsic and extrinsic factors. Cortical cholinergic
      regulation is a crucial factor for normal cortical morphogenesis. In this study,
      we test the role of the M1 muscarinic acetylcholine receptor, the main muscarinic
      receptor subtype in the neocortex in the development of tonotopic maps in the
      auditory cortex. Mice lacking M1 receptors have normal hearing sensitivity but
      exhibit disrupted tonotopic organization and frequency tuning in the auditory
      cortex. In contrast, tonotopic organization and frequency tuning remain normal in
      the auditory midbrain. In addition, cortical layer IV neurons of M1 mutants
      exhibit significantly shorter or sparser dendrites compared to neurons of
      wildtype mice. In summary, our data suggest that the M1 receptor appears to be
      critical for the refinement or normal maturation of cortical tonotopy that is
      guided by thalamocortical inputs during early development.

PMID- 15721571
TI  - Selective numbing and hyperarousal in male and female Bosnian refugees with PTSD.
AB  - Emotional numbing is an important symptom of PTSD, but it is not clear whether it
      affects both positive and negative affect equally or not. To address this
      question we administered Lang's Looking at Pictures test, in which a series of
      pictures are rated for valence (pleasant-unpleasant) and arousal (high-low), to
      10 male and 11 female Bosnian refugees suffering from PTSD (DSM-IV criteria) and
      to control groups of 11 male and 10 female Bosnian refugees with similar trauma
      exposure but without PTSD or any other major mental illness. The mean valence
      ratings for unpleasant, neutral, and pleasant pictures of both PTSD and control
      males and females were similar to normal ratings. Likewise, the mean arousal
      ratings for unpleasant, neutral, and pleasant pictures of both male and female
      controls were similar to normals, with both unpleasant and pleasant pictures
      rated more arousing than neutral pictures. In contrast, in both males and females
      with PTSD pleasant pictures were rated as almost completely non-arousing. Thus,
      in Bosnian refugees affective numbing is seen primarily with pleasant or positive
      stimuli.

PMID- 15721570
TI  - Cognitive behavioral and attachment based family therapy for anxious adolescents:
      Phase I and II studies.
AB  - The goals of these two studies were to assess the acceptability and feasibility
      as well as to gather preliminary efficacy data on a modified combination
      cognitive behavioral (CBT) and attachment based family therapy (ABFT) for
      adolescents (ages 12-18), with the primary diagnosis of generalized (GAD), social
      phobia (SP), and separation (SAD) anxiety disorders. In Phase I, CBT was modified
      for an adolescent population and ABFT was modified for working with anxious
      adolescents in combination with CBT. Therapists were trained for both conditions
      and eight patients were treated as an open trial pilot of combined CBT-ABFT with
      positive results. In Phase II, 11 adolescents were randomly assigned to CBT alone
      or CBT and family based treatment (CBT-ABFT). Participants were evaluated at pre,
      post, and 6-9 months follow-up assessing diagnosis, psychiatric symptoms and
      family functioning. Results indicated significant decreases in anxiety and
      depressive symptoms by both clinical evaluator and self-reports with no
      significant differences by treatment. Sixty-seven percent of adolescents in CBT
      no longer met criteria for their primary diagnosis at post treatment as compared
      to 40% in CBT-ABFT with continued improvement of 100 and 80% at follow-up with no
      significant differences between treatments. Both CBT and CBT-ABFT appear to be
      promising treatments for anxious adolescents and more treatment development and
      evaluation is needed.

PMID- 15721572
TI  - Disclosure of distress among anxiety-disordered youth: differences in treatment
      outcome.
AB  - The present study evaluated treatment outcome differences in anxiety-disordered
      youth who differed in their disclosure of internal distress as measured in a
      structured diagnostic interview. One hundred and seventy-one clinic-referred,
      anxiety-disordered children served as participants. Participants' primary
      diagnoses were one of three anxiety disorders: separation anxiety, generalized
      anxiety/overanxious, or social phobia/avoidance. At a pretreatment assessment,
      children and their parents were interviewed separately using the Anxiety
      Disorders Interview Schedule (ADIS) to determine the child's diagnosis. The
      child's status as a discloser of high distress or discloser of low distress was
      determined by the parents' endorsement of an anxiety disorder and the child's
      endorsement or lack of endorsement of an anxiety disorder, respectively. Parents,
      teachers, and children also completed measures assessing the child's
      psychopathology (e.g., Revised Children's Manifest Anxiety Scale, Child Behavior
      Checklist). In general, findings indicated that the level of distress reported by
      the children moderated treatment outcome. Although both groups benefited from
      treatment, the children disclosing high distress experienced greater treatment
      gains than the children disclosing low distress.

PMID- 15721573
TI  - A comparison between socially anxious and depressive symptomatology in youth: a
      focus on perceived family environment.
AB  - The current study employed present-oriented self-report measures to compare
      groups of socially anxious, depressed, mixed socially anxious and depressed, and
      comparison youth on perceptions of the family environment, as assessed via the
      Family Environment Questionnaire (FEQ). Results indicated that the mixed and
      depressed groups rated their parents as being overly concerned with others'
      opinions, feeling ashamed of their performance, and restricting family
      sociability more than the socially anxious and comparison groups. With respect to
      the latter two groups, the socially anxious group rated their family environment
      more negatively than the comparison group on each of these variables.
      Implications of the findings and directions for future research are discussed.

PMID- 15721574
TI  - Relationship between emotional numbing and arousal symptoms in American women of
      Japanese descent who experienced interpersonal victimization.
AB  - In recent years, studies of veterans and others who experienced various types of
      trauma have found a strong relationship between emotional numbing and arousal
      symptoms, challenging the current DSM-IV diagnostic criteria, which combines
      emotional numbing and avoidance symptoms in a single criterion. In this paper, we
      investigate emotional numbing symptoms in a community-based random sample of
      women of Japanese descent who had experienced interpersonal victimization, such
      as childhood abuse, intimate partner violence, and violence perpetrated by non
      intimates (n = 202). Controlling for age, place of birth, and timing and severity
      of victimization, emotional numbing symptom counts were associated more strongly
      with arousal than avoidance symptoms, consistent with previous studies of
      veterans and assaulted women. In addition, emotional numbing symptom counts were
      significantly associated with age and, to a lesser degree, country of birth.
      Implications for research and practice are discussed.

PMID- 15721575
TI  - Disgust as a motivator of avoidance of spiders.
AB  - Individuals with small animal phobias show elevated general disgust sensitivity,
      and spider phobics often endorse both fear and disgust in response to a spider.
      Some researchers have argued that the link between disgust and fear of small
      animals is spurious. On the other hand, disgust may play a functional role, as
      might any negative emotion that is strongly stimulus-bound, in which escape or
      avoidance is negatively reinforced. It is therefore important to clarify whether
      disgust has a functional or epiphenomenal role in avoidance of feared stimuli.
      The present study examined the degree to which disgust motivates avoidance of
      spider-related stimuli using a series of behavioral avoidance tests comparing a
      harmless tarantula, a pen that had come in contact with the spider, and a clean
      pen. Peak disgust was a stronger predictor than anxiety of avoidance of both the
      spider and the "contaminated" pen.

PMID- 15721576
TI  - TOM software toolbox: acquisition and analysis for electron tomography.
AB  - Automated data acquisition procedures have changed the perspectives of electron
      tomography (ET) in a profound manner. Elaborate data acquisition schemes with
      autotuning functions minimize exposure of the specimen to the electron beam and
      sophisticated image analysis routines retrieve a maximum of information from
      noisy data sets. "TOM software toolbox" integrates established algorithms and new
      concepts tailored to the special needs of low dose ET. It provides a user
      friendly unified platform for all processing steps: acquisition, alignment,
      reconstruction, and analysis. Designed as a collection of computational
      procedures it is a complete software solution within a highly flexible framework.
      TOM represents a new way of working with the electron microscope and can serve as
      the basis for future high-throughput applications.

PMID- 15721577
TI  - Effect of the covalently linked fatty acid 18-MEA on the nanotribology of hair's
      outermost surface.
AB  - Highly ordered lipids adsorbed or grafted on surfaces are known to provide
      protection and lubrication custom engineered surfaces. We have used atomic force
      microscopy (AFM) to measure adhesion and frictional properties of the outermost
      surfaces of a variety of human hairs with the aim of both understanding the role
      of 18-methyleicosanoic acid (18-MEA), an unusual branched-chain fatty acid
      covalently bound to the cuticle surface, and investigating how treatments or the
      ethnic origin affect this layer. Results show that an unmodified silicon nitride
      AFM tip is able to detect changes at the hair surface that can be related to the
      absence or presence of this layer due to treatment conditions and in particular
      that this monolayer has a lubricant effect.

PMID- 15721578
TI  - Spectral signal-to-noise ratio and resolution assessment of 3D reconstructions.
AB  - Measuring the quality of three-dimensional (3D) reconstructed biological
      macromolecules by transmission electron microscopy is still an open problem. In
      this article, we extend the applicability of the spectral signal-to-noise ratio
      (SSNR) to the evaluation of 3D volumes reconstructed with any reconstruction
      algorithm. The basis of the method is to measure the consistency between the data
      and a corresponding set of reprojections computed for the reconstructed 3D map.
      The idiosyncrasies of the reconstruction algorithm are taken explicitly into
      account by performing a noise-only reconstruction. This results in the definition
      of a 3D SSNR which provides an objective indicator of the quality of the 3D
      reconstruction. Furthermore, the information to build the SSNR can be used to
      produce a volumetric SSNR (VSSNR). Our method overcomes the need to divide the
      data set in two. It also provides a direct measure of the performance of the
      reconstruction algorithm itself; this latter information is typically not
      available with the standard resolution methods which are primarily focused on
      reproducibility alone.

PMID- 15721579
TI  - Atomic force microscopy investigation of a chlorella virus, PBCV-1.
AB  - A virus PBCV-1, which infects certain fresh water algae and has been shown by
      transmission and cryo-electron microscopy to exist as a triskaidecahedron, was
      imaged using atomic force microscopy (AFM). From AFM the particles have diameters
      of about 190nm and the overall structure is in all important respects consistent
      with existing models. The surface lattice of the virion is composed of trimeric
      capsid proteins distributed according to p3 symmetry to create a honeycomb
      arrangement of raised edges forming quasi-hexagonal cells. At the pentagonal
      vertices are five copies of a different protein forming an exact pentagon, and
      this has yet another unique protein in its center. The apical protein exhibits
      some unusual mechanical properties in that it can be made to retract into the
      virion interior when subjected to AFM tip pressure. When PBCV-1 virions degrade,
      they give rise to small, uniform, spherical, and virus like particles (VLP)
      consistent with T=1 or 3 icosahedral products. Also observed upon disintegration
      are strands of linear dsDNA. Fibers of unknown function are also occasionally
      seen associated with some virions.

PMID- 15721580
TI  - Crystal structure of a carbohydrate induced homodimer of phospholipase A2 from
      Bungarus caeruleus at 2.1A resolution.
AB  - This is the first crystal structure of a carbohydrate induced dimer of
      phospholipase A(2) (PLA(2)). This is an endogenous complex formed between two
      PLA(2) molecules and two mannoses. It was isolated from Krait venom (Bungarus
      caeruleus) and crystallized as such. The complete amino acid sequence of PLA(2)
      was determined using cDNA method. Three-dimensional structure of the complex has
      been solved with molecular replacement method and refined to a final R-factor of
      0.192 for all the data in the resolution range 20.0-2.1A. The presence of mannose
      molecules in the protein crystals was confirmed using dinitrosalicylic acid test
      and the molecular weight of the dimer was verified with MALDI-TOF. As indicated
      by dynamic light scattering and analytical ultracentrifugation the dimer was also
      stable in solution. The good quality non-protein electron density at the
      interface of two PLA(2) molecules enabled us to model two mannoses. The mannoses
      are involved extensively in interactions with protein atoms of both PLA(2)
      molecules. Some of the critical amino acid residues such as Asp 49 and Tyr 31,
      which are part of the substrate-binding site, are found facing the interface and
      interacting with mannoses. The structure of the complex clearly shows that the
      dimerization is caused by mannoses and it results in the loss of enzymatic
      activity.

PMID- 15721581
TI  - Specificity in the coacervation of tropoelastin: solvent exposed lysines.
AB  - Tropoelastin protein monomers associate by coacervation and are cross-linked in
      vivo to form elastin macro-assemblies. We provide evidence for specific protein
      domain contact points between tropoelastin monomers during association by
      coacervation. The homobifunctional cross-linker bis(sulfosuccinimidyl) suberate
      served as a rapid reporter of adjacent lysines and preferentially exposed
      domains. Intact cross-linked peptide pairs were identified after protease
      digestion and high-resolution electrospray mass spectrometry followed by MS/MS
      sequencing. Mapping of the assigned sequences indicated that the region in the
      monomer spanning domains 19-25 was readily accessible to solvent and enriched in
      cross-linking. Domains 12 and 36 were also prevalent, where these two regions
      were not previously thought to play a major role in the formation of mature
      elastin. A specificity for particular lysines allowed for the construction of a
      model for the first close contacts between domains and the first detailed study
      of the cross-linking of tropoelastin.

PMID- 15721582
TI  - A model two-component system for studying the architecture of elastin assembly in
      vitro.
AB  - Tropoelastin is encoded by a single human gene that spans 36 exons and is
      oxidized in vivo by mammalian lysyl oxidase at the epsilon amino group of
      available lysines to give the adipic semialdehyde, which then facilitates
      covalent cross-link formation in an enzyme-free process involving tropoelastin
      association. We demonstrate here that this process is effectively modeled by a
      two protein component system using purified lysyl oxidase from the yeast Pichia
      pastoris to facilitate the oxidation and subsequent cross-linking of recombinant
      human tropoelastin. The oxidized human tropoelastin forms an elastin-like polymer
      (EL) that is elastic, shows hydrogel behavior and contains typical elastin cross
      links including lysinonorleucine, allysine aldol, and desmosine. Protease
      digestion and subsequent mass-spectrometry analysis of multiple ELs allowed for
      the identification of specific intra- and inter-molecular cross-links, leading to
      a model of the molecular architecture of elastin assembly in vitro. Specific
      intra-molecular cross-links were confined to the region of tropoelastin encoded
      by exons 6-15. Inter-molecular cross-links were prevalent between the regions
      encoded by exons 19-25. We find that assembly of tropoelastin molecules in ELs
      are highly enriched for a defined subset of cross-links.

PMID- 15721583
TI  - Identification of the beta1-integrin binding site on alpha-actinin by
      cryoelectron microscopy.
AB  - Cell-matrix adhesions in migrating cells are usually mediated by integrins, alpha
      beta heterodimeric transmembrane proteins that link extracellular matrix
      molecules such as fibronectin to the cytoskeleton. We have synthesized the
      cytoplasmic domain of the beta1-integrin (residues H738-K778) with a histidine
      tag at its N-terminus. The binding of this peptide to a lipid monolayer
      containing a chelated-nickel group (dimyristoylphosphatidyl choline-suberimide
      nitriloacetic acid:nickel salt) mimics the native environment at the cytoplasmic
      leaflet of the plasma membrane. A Nanogold particle was covalently linked to
      cysteines introduced at the C-terminus and after residue T757 on the integrin
      peptide, and co-crystallized with chicken smooth muscle alpha-actinin. The 2-D
      arrays of the beta1-integrin-alpha-actinin complex were examined by cryoelectron
      microscopy, with and without the gold label. Averaged projections were calculated
      for each specimen along with a difference map to determine the relative position
      of the gold-labeled beta1-integrin peptide. The difference maps indicate that the
      beta1-integrin cytoplasmic domain binds alpha-actinin between the first and
      second, 3-helix motifs in the central rod domain.

PMID- 15721584
TI  - The mammalian cardiac muscle thick filament: crossbridge arrangement.
AB  - Although skeletal muscle thick filaments have been extensively studied,
      information on the structure of cardiac thick filaments is limited. Since cardiac
      muscle differs in many physiological properties from skeletal muscle it is
      important to elucidate the structure of the cardiac thick filament. The structure
      of isolated and negatively stained rabbit cardiac thick filaments has been
      analyzed from computed Fourier transforms and image analysis. The transforms are
      detailed, showing a strong set of layer lines corresponding to a 42.9 nm quasi
      helical repeat. The presence of relatively strong "forbidden" meridional
      reflections not expected from ideal helical symmetry on the second, fourth,
      fifth, seventh, eighth, and tenth layer lines suggest that the crossbridge array
      is perturbed from ideal helical symmetry. Analysis of the phase differences for
      the primary reflections on the first layer line of transforms from 15 filaments
      showed an average difference of 170 degrees, close to the value of 180 degrees
      expected for an odd-stranded structure. Computer-filtered images of the isolated
      thick filaments unequivocally demonstrate a three-stranded arrangement of the
      crossbridges on the filaments and provide evidence that the crossbridge
      arrangement is axially perturbed from ideal helical symmetry.

PMID- 15721585
TI  - The mammalian cardiac muscle thick filament: backbone contributions to meridional
      reflections.
AB  - Information about the structure of the vertebrate striated muscle thick filament
      backbone is important for understanding the arrangement of both the rod portion
      of the myosin molecule and the accessory proteins associated with the backbone
      region of the filament. Although models of the backbone have been proposed,
      direct data on the structure of the backbone is limited. In this study, we
      provide evidence that electron micrographs of isolated negatively stained cardiac
      thick filaments contain significant information about the filament backbone.
      Computed Fourier transforms from isolated cardiac thick filaments show meridional
      (or near meridional) reflections on the 10th and 11th layer lines that are
      particularly strong. Comparison of Fourier filtrations of the filaments that
      exclude, or include, these reflections, provide evidence that these reflections
      originate at least in part from a series of striations on the backbone at a
      approximately 4 nm spacing. The striations are likely to result either from the
      packing of the myosin rods, or from proteins such as titin associated with the
      filament backbone.

PMID- 15721586
TI  - Single particle electron microscopy in combination with mass spectrometry to
      investigate novel complexes of membrane proteins.
AB  - Large data sets of molecular projections of the membrane proteins Photosystem I
      and Photosystem II from cyanobacteria were analyzed by single particle electron
      microscopy (EM). Analysis resulted in the averaging of 2D projections from the
      purified complexes but also in the simultaneous detection and averaging of 2D
      projections from large contaminating complexes, which were present in frequencies
      as low as 0.1%. Among them T-shaped and L-shaped contaminants were found. The L
      shaped particles could be assigned to Complex I just from the shape, although no
      Complex I from a cyanobacterium has been structurally characterized. A systematic
      comparison by single particle EM and mass spectrometry of two differently
      purified Photosystem II complexes resulted in the assignment of PsbZ, a small
      peripheral subunit of 6.8kDa, within the structure. Together these data suggest
      that screening for membrane protein structures by single particle EM and mass
      spectrometry may be a new approach to find novel structures of such proteins. We
      propose here a scheme for searching for novel membrane protein structures in
      specific types of membranes. In this approach single particle EM and mass
      spectrometry, after pre-fractionation using one- or multidimensional protein
      separation techniques, are applied to characterize all its larger components.

PMID- 15721587
TI  - Crystal structure of a cross-reaction complex between an anti-HIV-1 protease
      antibody and an HIV-2 protease peptide.
AB  - The monoclonal antibody 1696, elicited by HIV-1 protease, inhibits the activity
      of both HIV-1 and HIV-2 proteases with inhibition constants in the low nanomolar
      range. The antibody cross-reacts with peptides derived from the N-terminal region
      of both proteases. The crystal structure of the recombinant single-chain Fv
      fragment of 1696 complexed with an N-terminal peptide from the HIV-2 protease has
      been determined at 1.88A resolution. Interactions of the peptide with scFv1696
      are compared with the previously reported structure of scFv1696 in complex with
      the corresponding peptide from HIV-1 protease. The origin of cross-reactivity of
      mAb1696 with HIV proteases is discussed.

PMID- 15721588
TI  - New diagnostic tests for pulmonary emboli.

PMID- 15721589
TI  - The short-term clinical outcomes after saline infusion sonohysterography in women
      with postmenopausal bleeding.
AB  - RATIONALE AND OBJECTIVE: To describe the short-term clinical outcomes of women
      with postmenopausal bleeding (PMB) who underwent saline-infused sonohysterography
      (SIS) and the impact of SIS results on clinical management. MATERIALS AND
      METHODS: A retrospective review of the Radiology Information Systems database
      identified 786 women who underwent SIS between February 1998 and October 2002. Of
      this group, 144 women (mean age, 60; range, 42-83) presented with PMB. The
      following clinical data were extracted from the electronic medical record: date
      of birth, hormone replacement therapy (HRT) status, SIS results, and clinical
      management before and after the SIS procedure. We categorized post-SIS clinical
      management into three categories: additional diagnostic or therapeutic procedure
      performed; HRT change or addition; or no change in clinical management. Between
      group comparisons were performed using a chi2 test. RESULTS: Of the 144 women
      with postmenopausal bleeding who underwent SIS, 119 (82.6%) successfully
      completed the SIS. Eighty women (67.2%) had a positive SIS exam. Abnormalities
      detected including polyps (n = 42); submucosal fibroids (n = 6); endometrial
      thickening (n = 8); a combination of 2 or more of the above (n = 7), or other
      abnormalities (debris, adenomyosis, or indeterminate findings, n = 17). Of the
      women with a positive SIS exam, 58% received subsequent diagnostic/therapeutic
      procedures compared to 5% of women who had a negative SIS (P < 0.001).
      Conversely, 59% of women with a negative SIS had no change in clinical management
      compared to 17.5% who had a positive SIS (P < 0.001). CONCLUSION: The trend in
      short-term clinical management is to pursue more aggressive subsequent diagnostic
      or treatment procedures if findings are positive on SIS. A negative SIS exam was
      associated with more conservative management.

PMID- 15721590
TI  - Magnetic field strength increase yields significantly greater contrast-to-noise
      ratio increase: Measured using BOLD contrast in the primary visual area.
AB  - RATIONALE AND OBJECTIVE: The advantage of a higher static magnetic field for
      functional MRI has been advocated; however, the observed advantage varies. The
      aim of this study was to evaluate the effect of increasing static magnetic field
      strength on the task-related increase in blood oxygenation level-dependent (BOLD)
      signal and residual noise with visual stimuli of different frequencies, which may
      enable better comparisons of results of different MRI scanners. MATERIALS AND
      METHODS: Eight right-handed healthy volunteers were presented checkerboard
      stimuli flickering at 5 different frequencies up to 8 Hz. Field strengths of 3 T
      or 1.5 T were used to measure frequency-dependent signal changes in the primary
      visual area. Regression analysis was performed for the signal increase and the
      "noise," which was defined by the root mean of squares of the residual signal
      fluctuation. These values were compared and their relationship was analyzed.
      Imaging parameters were identical except for the use of a 25% shorter echo time
      using 3 T. RESULTS: The frequency-dependent increase in BOLD signal using 3 T was
      twice that using 1.5 T. In contrast, the ratio of noise values that reflect time
      course signal fluctuation (3 T/1.5 T) was only 0.88. There was large individual
      variance in these values, but the slope and noise values were linearly related
      using either field strength. The contrast-to-noise ratio using 3 T was 2.3 times
      higher than that using 1.5 T. CONCLUSION: There was a greater-than-linear
      increase in the contrast-to-noise ratio compared with the increase of field
      strength, demonstrating an advantage of using higher field strengths in fMRI
      studies.

PMID- 15721591
TI  - Clinical potentials of the prototype 256-detector row CT-scanner.
AB  - RATIONALE AND OBJECTIVES: To evaluate clinical potentials of the 256-detector row
      computed tomography (CT) in healthy volunteers. MATERIALS AND METHODS: Eight
      healthy males (22-63 years) participated in the present study. They underwent a
      noncontrast-enhanced examination with a contiguous axial scan mode either for
      head, chest, abdomen, or pelvis. Dose was the same as routinely used for
      multislice CT examinations. Image quality was interpreted by three board
      certified radiologists. RESULTS: With the 256-detector row CT, 0.5-0.8 mm
      isotropic volumetric data could be acquired in one rotation. Main promising
      findings are as follows. Three-dimensional structures were visualized clearly in
      the multiple planes without secondary reconstruction, whereas the axial images
      had nearly the same image quality as conventional CT. Shading or streak artifacts
      were observed at the edge of the scan region. The latter are also known as
      Feldkamp artifacts. Coronal chest images showed a motion artifact from the heart
      beating. CONCLUSION: The 256-detector row CT promises to be useful in clinical
      applications with its ability to provide three-dimensional visualization of fine
      structures. The Feldkamp artifacts observed did not generally affect
      interpretation of images. Investigations are now continuing on image correction
      along the craniocaudal direction to improve the overall image quality.

PMID- 15721592
TI  - 3D contrast-enhanced MR angiography of the abdominal aorta and its distal
      branches: Interobserver agreement of radiologists in a routine examination.
AB  - RATIONALE AND OBJECTIVES: To evaluate the quality of images of the aorta and
      visceral arteries made at a high level of spatial resolution with thin slices and
      an optimized acquisition time by three-dimensional contrast-enhanced magnetic
      resonance angiography (3D CE-MRA). MATERIALS AND METHODS: 3D CE-MRA with a 1.4-mm
      slice thickness and 512-pixel base matrix was done on 62 consecutive patients
      with a 1.5-T magnetic resonance imaging MRI unit. A bolus test with a power
      injector was used to calculate the optimal scan delay time. For quantitative
      evaluation, the signal-to-noise ratio (SNR) was measured in 3 regions of
      interest. Qualitative image analysis was evaluated independently by two
      radiologists and graded on a scale of 0-3. Separate analyses were done for the
      aorta and distal visceral arterial branches. RESULTS: The means SNR values were
      respectively 56.2 +/- 15.2 (mean +/- SD) for the aorta, 59.2 +/- 15.1 for the
      celiac trunk, and 57 +/- 15.2 for the superior mesenteric artery, with a
      homogeneous distribution (P = .99). Consistent enhancement was confirmed by the
      lack of statistically significant differences between the SNR values. The average
      score for vessel visualization on source images ranged from good to excellent for
      different segments. After post-processing of images, the average score for distal
      arterial segments was significantly improved. The overall agreement between the 2
      reviewers in the visualization of definite artery segments was excellent (k =
      .91). CONCLUSION: 3D CE-MRA with a 512-pixel base matrix and thin slices can be
      applied in a reproducible way with excellent depiction and delineation of small
      vessels. Such a protocol could be used routinely.

PMID- 15721593
TI  - Neural correlates of telling lies: a functional magnetic resonance imaging study
      at 4 Tesla.
AB  - RATIONALE AND OBJECTIVE: Intentional deception (ie, lying) is a complex cognitive
      act, with important legal, moral, political, and economic implications. Prior
      studies have identified activation of discrete anterior frontal regions, such as
      the ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex
      (DLPFC), dorsal medial prefrontal cortex (DMPFC), and anterior cingulate cortex
      (ACC) during deception. To extend these findings, we used novel real-time
      functional magnetic resonance imaging (fMRI) technology to simulate a polygraph
      experience in order to evoke performance anxiety about generating lies, and
      sought to ascertain the neural correlates of deception. MATERIALS AND METHODS: In
      this investigational fMRI study done with a 4-T scanner, we examined the neural
      correlates of lying in 14 healthy adult volunteers while they performed a
      modified card version of the Guilty Knowledge Test (GKT), with the understanding
      that their brain activity was being monitored in real time by the investigators
      conducting the study. The volunteers were instructed to attempt to generate Lies
      that would not evoke changes in their brain activity, and were told that their
      performance and brain responses were being closely monitored. RESULTS: Subjects
      reported performance anxiety during the task. Deceptive responses were
      specifically associated with activation of the VLPFC, DLPFC, DMPFC, and superior
      temporal sulcus. DISCUSSION: These findings suggest the involvement of discrete
      regions of the frontal cortex during lying, and that the neural substrates
      responsible for cognitive control of behavior may also be engaged during
      deception.

PMID- 15721594
TI  - Image quality of volume rendering of the bronchial tree: Kymogram-gated versus
      retrospectively ECG-gated and non-gated multi-row detector CT.
AB  - RATIONALE AND OBJECTIVE: To compare the image quality of three different heart
      cycle-synchronized computed tomography (CT) reconstruction algorithms for volume
      rendered (VR) 3D visualization of the bronchial tree. MATERIALS AND METHODS:
      Kymogram-gated, retrospectively ECG-gated, and non-ECG-gated reconstructions of
      the bronchial tree were performed from 4-detector-row CT data in 10 subjects. The
      raw data were reconstructed in 10 phases of the cardiac cycle using ECG-gated and
      kymogram-gated technique, respectively. For both reconstructions, the optimal
      artifact-free diastolic phase was determined. VR reconstructions of the bronchial
      tree were generated from these two data sets and from the non-gated data.
      Stairstep artifacts of the main bronchi, artifacts in the lung parenchyma, and
      the extent of bronchial tree visualization were rated by two blinded, independent
      readers. RESULTS: Kymogram-gated reconstruction showed stairstep artifacts in the
      main bronchi to the same extent as non-gated reconstruction, but less compared to
      ECG-gated reconstruction (P < .001). Artifacts in the lung parenchyma were
      similar with kymogram-gated and non-gated reconstruction, but less compared to
      ECG-gated reconstruction (P < 0.01). Kymogram-gated reconstruction showed no
      differences in visualization of segmental and subsegmental bronchi compared to
      ECG-gated reconstruction, but was inferior to the non-gated reconstruction (P <
      0.05). CONCLUSION: Kymogram-gated reconstruction of CT data results in fewer
      artifacts when compared to the ECG-gated algorithm. Best visualization of the
      bronchial tree at a low artifact level is obtained with non-gated CT data. It
      remains therefore the method of choice for VR 3D data post-processing of the
      bronchial tree.

PMID- 15721595
TI  - Automated seed placement for colon segmentation in computed tomography
      colonography.
AB  - RATIONALE AND OBJECTIVE: To present an algorithm to automatically locate seeds
      for colon segmentation in computed tomography colonography (CTC). MATERIALS AND
      METHODS: The algorithm automatically locates two points (seeds) inside the colon
      lumen. Because of their high distention and fixed anatomic position, we focus on
      the cecum and rectum for automatic seed placement. We use two-dimensional
      morphological operators that find pockets of colonic air of sufficient size. For
      the rectum, we search within an inferiorly and centrally located CT slice. For
      the cecum, we search in a group of CT slices in the middle of the scanned volume
      on the patient's right side. We applied our automated algorithm to segment the
      colon in 292 consecutive cases of CTC (146 prone, 146 supine). RESULTS: After
      automated seed placement, 83.2% (243 of 292) of the colons were segmented
      completely and 9.6% (28 of 292) were segmented partially. The unsegmented colon
      parts were present in datasets where the colon was collapsed in more than one
      place or because seeds could not be placed in regions filled with fluid. In the
      remaining 7.2% (21 of 292) of cases, the automatic segmentation leaked outside
      the colon because of a limitation of the contrast-enhanced fluid detection
      algorithm. CONCLUSION: Fully automatic seed placement for colonic segmentation is
      feasible in the majority of cases without seeding of undesired extracolonic air.

PMID- 15721596
TI  - False-positive reduction in computer-aided diagnostic scheme for detecting
      nodules in chest radiographs by means of massive training artificial neural
      network.
AB  - RATIONALE AND OBJECTIVE: We developed a technique that uses a multiple massive
      training artificial neural network (multi-MTANN) to reduce the number of false
      positive results in a computer-aided diagnostic (CAD) scheme for detecting
      nodules in chest radiographs. MATERIALS AND METHODS: Our database consisted of 91
      solitary pulmonary nodules, including 64 malignant nodules and 27 benign nodules,
      in 91 chest radiographs. With our current CAD scheme based on a difference-image
      technique and linear discriminant analysis, we achieved a sensitivity of 82.4%,
      with 4.5 false positives per image. We developed the multi-MTANN for further
      reduction of the false positive rate. An MTANN is a highly nonlinear filter that
      can be trained with input images and corresponding teaching images. To reduce the
      effects of background levels in chest radiographs, we applied a background-trend
      correction technique, followed by contrast normalization, to the input images for
      the MTANN. For enhancement of nodules, the teaching image was designed to contain
      the distribution for a "likelihood of being a nodule." Six MTANNs in the multi
      MTANN were trained by using typical nodules and six different types of non
      nodules (false positives). RESULTS: Use of the trained multi-MTANN eliminated
      68.3% of false-positive findings with a reduction of one true-positive result.
      The false-positive rate of our original CAD scheme was improved from 4.5 to 1.4
      false positives per image, at an overall sensitivity of 81.3%. CONCLUSION: Use of
      a multi-MTANN substantially reduced the false-positive rate of our CAD scheme for
      lung nodule detection on chest radiographs, while maintaining a level of
      sensitivity.

PMID- 15721598
TI  - Revised curriculum on cardiothoracic radiology for diagnostic radiology residency
      with goals and objectives related to general competencies.
AB  - This document is a revision of a previously published cardiothoracic curriculum
      for diagnostic radiology residency, and reflects interval changes in the clinical
      practice of cardiothoracic radiology and changes in the Accreditation Council for
      Graduate Medical Education (ACGME) requirements for diagnostic radiology training
      programs. The revised ACGME Program Requirements for Residency Education in
      Diagnostic Radiology went into effect December 2003.

PMID- 15721597
TI  - Feasibility of combining MR perfusion, angiography, and 3He ventilation imaging
      for evaluation of lung function in a porcine model.
AB  - RATIONALE AND OBJECTIVE: To assess the feasibility of combining magnetic
      resonance (MR) perfusion, angiography, and 3He ventilation imaging for the
      evaluation of lung function in a porcine model. MATERIALS AND METHODS: Fourteen
      consecutive porcine models with externally delivered pulmonary emboli and/or
      airway occlusions were examined with MR perfusion, angiography, and 3He
      ventilation imaging. Ultrafast gradient-echo sequences were used for 3D perfusion
      and angiographic imaging, in conjunction with the use of contrast-agent
      injections. 2D multiple-section 3He imaging was performed subsequently via the
      inhalation of hyperpolarized 3He gas. The diagnostic accuracy of MR angiography
      for detecting pulmonary emboli was determined by two reviewers. The diagnostic
      confidence for different combinations of MR techniques was rated on the basis of
      a 5-point grading scale (5 = definite). RESULTS: The sensitivity, specificity,
      and accuracy of MR angiography for detecting pulmonary emboli were approximately
      85.7%, 90.5%, and 88.1%, respectively. The interobserver agreement was very
      strong (k = 0.82). There was a clear tendency for confidence to increase when
      first perfusion and then ventilation imaging were added to the angiographic image
      (Wilcoxon signed ranks test, P = 0.03). CONCLUSION: The combination of the three
      methods of MR perfusion, angiography, and 3H ventilation imaging may provide
      complementary information on abnormal lung anatomy and function.

PMID- 15721599
TI  - Postgraduate radiology training in sub-Saharan Africa: a review of current
      educational resources.
AB  - RATIONALE AND OBJECTIVE: Postgraduate training programs in radiology exist in
      several African nations. The ability of these programs to train radiologists is
      necessarily affected by local availability of educational resources, including
      clinical case volume, radiology equipment and maintenance, number of teaching
      faculty, and library and computer facilities. We sought to determine the current
      resources of a sample of African radiology education programs. MATERIALS AND
      METHODS: Site visits were conducted at three separate radiology training
      programs, one in Ghana and two in South Africa. At each site, the investigator
      conducted a technology census, assessed library resources, observed daily trainee
      activities, and interviewed trainees, faculty, and statisticians. RESULTS:
      African radiology trainees receive considerable training in fluoroscopy,
      ultrasound, and plain film radiography, but receive considerably less training in
      nuclear medicine, mammography, magnetic resonance imaging, and interventional
      radiology. A large amount of equipment in African teaching hospitals is
      inoperative because of lack of maintenance programs. Faculty to resident ratios
      in African teaching hospitals are much lower than in American hospitals. Needs of
      training programs vary greatly from hospital to hospital, and from country to
      country. CONCLUSION: Radiologists, radiology organizations, and radiology vendors
      from high-income nations are in a unique position to help Africa's postgraduate
      radiology training programs fulfill their mission of training Africa's next
      generation of radiologists. It is desirable that long-term commitments be made to
      teaching hospitals so that scarce donated resources may be put to the best
      possible use.

PMID- 15721600
TI  - Cultural competency in diagnostic imaging.

PMID- 15721603
TI  - Light-driven enzymatic catalysis of DNA repair: a review of recent biophysical
      studies on photolyase.
AB  - More than 50 years ago, initial experiments on enzymatic photorepair of
      ultraviolet (UV)-damaged DNA were reported [Proc. Natl. Acad. Sci. U. S. A. 35
      (1949) 73]. Soon after this discovery, it was recognized that one enzyme,
      photolyase, is able to repair UV-induced DNA lesions by effectively reversing
      their formation using blue light. The enzymatic process named DNA
      photoreactivation depends on a non-covalently bound cofactor, flavin adenine
      dinucleotide (FAD). Flavins are ubiquitous redox-active catalysts in one- and two
      electron transfer reactions of numerous biological processes. However, in the
      case of photolyase, not only the ground-state redox properties of the FAD
      cofactor are exploited but also, and perhaps more importantly, its excited-state
      properties. In the catalytically active, fully reduced redox form, the FAD
      absorbs in the blue and near-UV ranges of visible light. Although there is no
      direct experimental evidence, it appears generally accepted that starting from
      the excited singlet state, the chromophore initiates a reductive cleavage of the
      two major DNA photodamages, cyclobutane pyrimidine dimers and (6-4)
      photoproducts, by short-distance electron transfer to the DNA lesion. Back
      electron transfer from the repaired DNA segment is believed to eventually restore
      the initial redox states of the cofactor and the DNA nucleobases, resulting in an
      overall reaction with net-zero exchanged electrons. Thus, the entire process
      represents a true catalytic cycle. Many biochemical and biophysical studies have
      been carried out to unravel the fundamentals of this unique mode of action. The
      work has culminated in the elucidation of the three-dimensional structure of the
      enzyme in 1995 that revealed remarkable details, such as the FAD-cofactor
      arrangement in an unusual U-shaped configuration. With the crystal structure of
      the enzyme at hand, research on photolyases did not come to an end but, for good
      reason, intensified: the geometrical structure of the enzyme alone is not
      sufficient to fully understand the enzyme's action on UV-damaged DNA. Much effort
      has therefore been invested to learn more about, for example, the geometry of the
      enzyme-substrate complex, and the mechanism and pathways of intra-enzyme and
      enzyme <-->DNA electron transfer. Many of the key results from biochemical and
      molecular biology characterizations of the enzyme or the enzyme-substrate complex
      have been summarized in a number of reviews. Complementary to these articles,
      this review focuses on recent biophysical studies of photoreactivation comprising
      work performed from the early 1990s until the present.

PMID- 15721604
TI  - C-C bond formation and cleavage in radical enzymes, a theoretical perspective.
AB  - Quantum chemical methods are today a viable tool in the study of enzyme
      catalysis. The development of new density functional techniques and the enormous
      advancement in computer power have made it possible to accurately describe active
      sites of enzymes. This review gives a brief account of the methods and models
      used in this field. Three specific enzymes are discussed: pyruvate-formate lyase
      (PFL), spore photoproduct lyase (SPL), and benzylsuccinate synthase (BSS). What
      these enzymes have in common is that they use radical chemistry to catalyze C-C
      bond formation or cleavage reactions.

PMID- 15721605
TI  - Key enzymes in the anaerobic aromatic metabolism catalysing Birch-like
      reductions.
AB  - Several novel enzyme reactions have recently been discovered in the aromatic
      metabolism of anaerobic bacteria. Many of these reactions appear to be catalyzed
      by oxygen-sensitive enzymes by means of highly reactive radical intermediates.
      This contribution deals with two key reactions in this metabolism: the ATP-driven
      reductive dearomatisation of the benzene ring and the reductive removal of a
      phenolic hydroxyl group. The two reactions catalyzed by benzoyl-CoA reductase
      (BCR) and 4-hydroxybenzoyl-CoA reductase (4-HBCR) are both mechanistically
      difficult to achieve; both are considered to proceed in 'Birch-like' reductions
      involving single electron and proton transfer steps to the aromatic ring. The
      problem of both reactions is the extremely high redox barrier for the first
      electron transfer to the substrate (e.g., -1.9 V in case of a benzoyl-CoA (BCoA)
      analogue), which is solved in the two enzymes in different manners. Studying
      these enzymatic reactions provides insights into general principles of how oxygen
      dependent reactions are replaced by alternative processes under anoxic
      conditions.

PMID- 15721606
TI  - Vibrational spectroscopy to study the properties of redox-active tyrosines in
      photosystem II and other proteins.
AB  - Tyrosine radicals play catalytic roles in essential metalloenzymes. Their
      properties--midpoint potential, stability...--or environment varies considerably
      from one enzyme to the other. To understand the origin of these properties, the
      redox tyrosines are studied by a number of spectroscopic techniques, including
      Fourier transform infrared (FTIR) and resonance Raman (RR) spectroscopy. An
      increasing number of vibrational data are reported for the (modified-) redox
      active tyrosines in ribonucleotide reductases, photosystem II, heme catalase and
      peroxidases, galactose and glyoxal oxidases, and cytochrome oxidase. The spectral
      markers for the tyrosinyl radicals have been recorded on models of (substituted)
      phenoxyl radicals, free or coordinated to metals. We review these vibrational
      data and present the correlations existing between the vibrational modes of the
      radicals and their properties and interactions formed with their environment: we
      present that the nu7a(C-O) mode of the radical, observed both by RR and FTIR
      spectroscopy at 1480-1515 cm(-1), is a sensitive marker of the hydrogen bonding
      status of (substituted)-phenoxyl and Tyr*, while the nu8a(C-C) mode may probe
      coordination of the Tyr* to a metal. For photosystem II, the information obtained
      by light-induced FTIR difference spectroscopy for the two redox tyrosines TyrD
      and TyrZ and their hydrogen bonding partners is discussed in comparison with
      those obtained by other spectroscopic methods.

PMID- 15721607
TI  - Structure and interactions of amino acid radicals in class I ribonucleotide
      reductase studied by ENDOR and high-field EPR spectroscopy.
AB  - This short review compiles high-field electron paramagnetic resonance (EPR) and
      electron nuclear double resonance (ENDOR) studies on different intermediate amino
      acid radicals, which emerge in wild-type and mutant class I ribonucleotide
      reductase (RNR) both in the reaction of protein subunit R2 with molecular oxygen,
      which generates the essential tyrosyl radical, and in the catalytic reaction,
      which involves a radical transfer between subunits R2 and R1. Recent examples are
      presented, how different amino acid radicals (tyrosyl, tryptophan, and different
      cysteine-based radicals) were identified, assigned to a specific residue, and
      their interactions, in particular hydrogen bonding, were investigated using high
      field EPR and ENDOR spectroscopy. Thereby, unexpected diiron-radical centers,
      which emerge in mutants of R2 with changed iron coordination, and an important
      catalytic cysteine-based intermediate in the substrate turnover reaction in R1
      were identified and characterized. Experiments on the essential tyrosyl radical
      in R2 single crystals revealed the so far unknown conformational changes induced
      by formation of the radical. Interesting structural differences between the
      tyrosyl radicals of class Ia and Ib enzymes were revealed. Recently accurate
      distances between the tyrosyl radicals in the protein dimer R2 could be
      determined using pulsed electron-electron double resonance (PELDOR), providing a
      new tool for docking studies of protein subunits. These studies show that high
      field EPR and ENDOR are important tools for the identification and investigation
      of radical intermediates, which contributed significantly to the current
      understanding of the reaction mechanism of class I RNR.

PMID- 15721608
TI  - EPR techniques for studying radical enzymes.
AB  - EPR studies on radical enzymes are reviewed under the aspects of the information
      that they can provide and of the techniques that are used. An overview of organic
      radicals derived from amino acids, modified amino acids, and cofactors is given
      and g tensor data are compiled. The information accessible from a spectroscopic
      point of view is contrasted with the information required to understand enzyme
      structure and function, and some precautions are discussed that must be taken to
      derive the latter kind of information from the former. Structural dynamics is
      identified as an aspect that has rarely been addressed in the past although it is
      highly relevant for enzyme function. It is proposed that techniques introduced
      recently on other classes of proteins could help to close this gap.

PMID- 15721609
TI  - Exploring amino-acid radical chemistry: protein engineering and de novo design.
AB  - Amino-acid radical enzymes are often highly complex structures containing
      multiple protein subunits and cofactors. These properties have in many cases
      hampered the detailed characterization of their amino-acid redox cofactors. To
      address this problem, a range of approaches has recently been developed in which
      a common strategy is to reduce the complexity of the radical-containing system.
      This work will be reviewed and it includes the light-induced generation of
      aromatic radicals in small-molecule and peptide systems. Natural redox proteins,
      including the blue copper protein azurin and a bacterial photosynthetic reaction
      center, have been engineered to introduce amino-acid radical chemistry. The
      redesign strategies to achieve this remarkable change in the properties of these
      proteins will be described. An additional approach to gain insights into the
      properties of amino-acid radicals is to synthesize de novo designed model
      proteins in which the redox chemistry of these species can be studied. Here we
      describe the design, synthesis and characteristics of monomeric three-helix
      bundle and four-helix bundle proteins designed to study the redox chemistry of
      tryptophan and tyrosine. This work demonstrates that de novo protein design
      combined with structural, electrochemical and quantum chemical analyses can
      provide detailed information on how the protein matrix tunes the thermodynamic
      properties of tryptophan.

PMID- 15721610
TI  - Transient radical pairs studied by time-resolved EPR.
AB  - Photogenerated short-lived radical pairs (RP) are common in biological
      photoprocesses such as photosynthesis and enzymatic DNA repair. They can be
      favorably probed by time-resolved electron paramagnetic resonance (EPR) methods
      with adequate time resolution. Two EPR techniques have proven to be particularly
      useful to extract information on the working states of photoinduced biological
      processes that is only difficult or sometimes even impossible to obtain by other
      types of spectroscopy. Firstly, transient EPR yields crucial information on the
      chemical nature and the geometry of the individual RP halves in a doublet-spin
      pair generated by a short laser pulse. This time-resolved method is applicable in
      all magnetic field/microwave frequency regimes that are used for continuous-wave
      EPR, and is nowadays routinely utilized with a time resolution reaching about 10
      ns. Secondly, a pulsed EPR method named out-of-phase electron spin echo envelope
      modulation (OOP-ESEEM) is increasingly becoming popular. By this pulsed
      technique, the mutual spin-spin interaction between the RP halves in a doublet
      spin pair manifests itself as an echo modulation detected as a function of the
      microwave-pulse spacing of a two-pulse echo sequence subsequent to a laser pulse.
      From the dipolar coupling, the distance between the radicals is readily derived.
      Since the spin-spin interaction parameters are typically not observable by
      transient EPR, the two techniques complement each other favorably. Both EPR
      methods have recently been applied to a variety of light-induced RPs in
      photobiology. This review summarizes the results obtained from such studies in
      the fields of plant and bacterial photosynthesis and DNA repair mediated by the
      enzyme DNA photolyase.

PMID- 15721611
TI  - Reaction of haem containing proteins and enzymes with hydroperoxides: the radical
      view.
AB  - The reaction between hydroperoxides and the haem group of proteins and enzymes is
      important for the function of many enzymes but has also been implicated in a
      number of pathological conditions where oxygen binding proteins interact with
      hydrogen peroxide or other peroxides. The haem group in the oxidized Fe3+
      (ferric) state reacts with hydroperoxides with a formation of the Fe4+=O
      (oxoferryl) haem state and a free radical primarily located on the pi-system of
      the haem. The radical is then transferred to an amino acid residue of the protein
      and undergoes further transfer and transformation processes. The free radicals
      formed in this reaction are reviewed for a number of proteins and enzymes. Their
      previously published EPR spectra are analysed in a comparative way. The radicals
      directly detected in most systems are tyrosyl radicals and the peroxyl radicals
      formed on tryptophan and possibly cysteine. The locations of the radicals in the
      proteins have been reported as follows: Tyr133 in soybean leghaemoglobin;
      alphaTyr42, alphaTrp14, betaTrp15, betaCys93, (alphaTyr24-alphaHis20), all in the
      alpha- and beta-subunits of human haemoglobin; Tyr103, Tyr151 and Trp14 in sperm
      whale myoglobin; Tyr103, Tyr146 and Trp14 in horse myoglobin; Trp14, Tyr103 and
      Cys110 in human Mb. The sequence of events leading to radical formation,
      transformation and transfer, both intra- and intermolecularly, is considered. The
      free radicals induced by peroxides in the enzymes are reviewed. Those include:
      lignin peroxidase, cytochrome c peroxidase, cytochrome c oxidase, turnip
      isoperoxidase 7, bovine catalase, two isoforms of prostaglandin H synthase,
      Mycobacterium tuberculosis and Synechocystis PCC6803 catalase-peroxidases.

PMID- 15721612
TI  - Imaging techniques in retinal research.
AB  - In recent years, retinal research has benefited from major advances in optical
      imaging approaches. Investigations of the structural and functional organization
      of the vertebrate retina using live preparations have been facilitated by
      improvements in cell labeling methods, and by microscopy techniques that permit
      high-resolution of cells in vitro and in vivo. In particular, the generation of
      transgenic animals with fluorescently labeled retinal cells has permitted real
      time visualization of cell generation, migration, differentiation and growth in
      the developing retina. Neuronal activity can also be examined by optical imaging
      using activity reporters directed to specific retinal cell types. Optical
      techniques such as multiphoton microscopy and total internal reflection
      fluorescence microscopy (TIRFM) have helped unravel the physiological properties
      and function of retinal cells. Here, we focus on the latest cell labeling methods
      that have proven highly useful in many aspects of retinal research. We also
      highlight several examples of how newly developed imaging technology itself has
      facilitated investigations that have advanced our understanding of retinal
      circuits and their development.

PMID- 15721613
TI  - Cl- concentrations of bovine, porcine and ovine aqueous humor are higher than in
      plasma.
AB  - Aqueous humor (AH) Cl- levels were measured from live cows and pigs to confirm
      the Cl(-)-secretory activities found across the ciliary bodies of these species
      in in vitro experiments. The values obtained were compared to those of the
      electrolyte in plasma (PL). In addition, Na+ and K+ concentrations were also
      measured in AH and PL. For analogy, the same measurements were made in sheep and
      rabbit. The results indicate that the Cl- AH-to-PL ratios of the bovine, porcine
      and ovine species, but not that of rabbit, are comparable to published values for
      humans. Thus, the transport activities of the ciliary epithelia of the former
      animals may be more adequate as a representative model for human than the
      commonly used rabbit, which exhibits strikingly different transport properties
      with a ciliary epithelium that is primarily a bicarbonate-transporting tissue.

PMID- 15721614
TI  - Delphinidin-3-rutinoside relaxes the bovine ciliary smooth muscle through
      activation of ETB receptor and NO/cGMP pathway.
AB  - Delphinidin-3-rutinoside (D3R) is the major anthocyanin component in blackcurrant
      (Ribes nigrum L.) fruits. We investigated the relaxation mechanism of D3R in
      bovine ciliary smooth muscle (CM). D3R at a concentration of 10(-5) m produced a
      sustained and progressive relaxation during the contraction induced by endothelin
      (ET)-1 in the bovine CM specimens. After the pre-treatment with D3R, the
      anthocyanin exerted an inhibitory effect on the ET-1-induced contraction with a
      concomitant increase in cyclic GMP production and decreased phosphorylation ratio
      of myosin light chain (RLC). The inhibitory effect of D3R was significantly
      attenuated in the presence of either N(G)-nitro-L-arginine (NOARG) as a nitric
      oxide synthase (NOS) inhibitor, carboxy-PTIO as a NO scavenger, ODQ as an
      inhibitor of guanylyl cyclase, or BQ788 as a selective ET(B) receptor antagonist.
      The atteuation with NOARG was reversed by the addition of excess L-arginine.
      However, iberiotoxin as a Ca2+-activated K+ channel inhibitor, propranolol as a
      beta-adrenoceptor antagonist, and indomethacin as a cyclooxygenase inhibitor
      failed to modify the inhibitory effect of D3R. Scatchard plot analysis revealed
      that the [125I]-ET-1 binding site constituted a single population with Kd of
      54.5+/-4.6 nm and maximum binding site (B(max)) of 168.4+/-25.4 fmol/mg protein
      in the ciliary epithelium (CE), and Kd of 141.7+/-18.0 nm and B(max) of 357.7+/
      35.8 fmol/mg protein in CM. [125I]-ET-1 binding was completely displaced by BQ788
      with K(i) values of 56.7+/-10.8 pm in CE and 93.4+/-23.3 pm in CM. Meanwhile,
      partial displacement (approximately 40%) was observed by BQ123 as a selective
      ET(A) receptor antagonist in both preparations. ET(B) receptor was predominant
      subtype in CE and CM, whereas kinetics of the binding was different in two
      preparations. These results suggest that D3R possibly stimulates ET(B) receptors
      to produce/release NO, and results in an inhibition of myosin RLC phosphorylation
      and/or acceleration of dephosphorylation, thereby causing relaxation and
      producing an inhibitory effect on the ET-1-induced contraction in the bovine CM.

PMID- 15721615
TI  - A spontaneous mutation affects programmed cell death during development of the
      rat eye.
AB  - We have discovered a spontaneous mutation in the Sprague-Dawley rat with a novel
      eye phenotype that we have named Nuc1. The Nuc1 mutation behaves as a single semi
      dominant locus with an intermediate phenotype in the heterozygotes. Heterozygotes
      exhibit nuclear cataracts. Homozygous Nuc1 rats are fully viable and have
      microphthalmia, retinal abnormalities and disruption of lens structure shortly
      before birth. The homozygous mutant shows no obvious pathology outside of the
      eye, indicating that the mutation is highly eye specific in its effects. An
      unusual feature of the mutation is that it prevents the normal programmed loss of
      nuclei from lens fiber cells, but does not affect the loss of other organelles.
      TUNEL, light, and electron microscopic studies show normal intact nuclei in lens
      fibers, in contrast to many other models with degenerate nuclei and unlike normal
      lenses where no such nuclei remain. The beaded filament protein, filensin, is
      down-regulated in fibers of Nuc1, while heat shock cognate 70 is up-regulated.
      Homozygous retinas are thicker than normal, and TUNEL labeling indicates roughly
      half the number of apoptotic cells compared to a wild-type retina. The transient
      layer of Chievitz persists in adult Nuc1 retina, indicative of delayed
      development. Hence, Nuc1 is a novel mutation that could be an eye-specific
      regulator of apoptosis.

PMID- 15721616
TI  - Alterations in human vitreous humour following cataract extraction.
AB  - Cataract extraction is associated with the risk of posterior vitreous detachment,
      macular edema and retinal detachment possibly as a result of a disturbance to the
      vitreous body during surgery. While it is common for lens cortical fiber debris
      to leak into the vitreous humour during cataract extraction, the extent to which
      the vitreous humour is altered post-surgery is unknown. The current study
      examines the integrity of the vitreous humour of pseudophakic and phakic human
      donor eyes by comparing the proteome, the viscosity and the size distribution of
      macromolecules in different regions of the vitreous humour from human
      pseudophakic and phakic donor eyes. Major differences between the proteomes of
      anterior and posterior vitreous humour were observed in phakic and pseudophakic
      donor eyes. Seventeen spots identified as complete, modified or cleaved forms of
      alphaA-, alphaB-, betaA4-, betaB2, and gammaS-crystallins were present in the
      anterior vitreous humour of all pseudophakic eyes studied. Crystallins were not
      detected in the posterior vitreous humour of the pseudophakic eye or the vitreous
      humour of the phakic eye. Significant alterations in abundance and/or
      modification of transthyretin, alpha antitrypsin, and retinoic acid binding
      protein were observed in all locations of pseudophakic vitreous humour as
      compared to phakic samples. In addition, a significant decrease in the number and
      intensity of protein spots was observed for the posterior vitreous humour of
      pseudophakic eyes when compared to posterior vitreous humour of phakic eyes.
      Proteins which were affected include antioxidant proteins and enzymes such as
      carbonic anhydrase and trisephosphate isomerase. A reversal of the viscosity
      gradient, anterior to posterior, in the vitreous humour of pseudophakic eyes was
      observed concomitant with alterations in the distribution of 50 nm particles.
      These particles are likely primarily composed of hyaluronan. While varying
      degrees of vitreous degradation may have existed prior to surgery and may have
      contributed to the cataract formation, in no case did the phakic donor eyes
      exhibit the same alterations in the vitreous humour proteome, viscosity or
      particle sizes as did the pseudophakic donor eyes. The examination of
      phakic/pseudophakic donor eye pairs confirmed that the vitreous humour proteome
      and structural integrity were very similar in the matched phakic donor eye to
      eyes from donors with no history of cataract. Even though the number of samples
      for this study was limited, the observed changes support the hypothesis that
      alterations in the vitreous humour proteome occur in psuedophakic eyes with
      concurrent alterations in the structure of the vitreous humor. These
      modifications of the microenvironment of the retina may contribute to the
      development of retinal complications following cataract surgery.

PMID- 15721617
TI  - The relationship between refractive and biometric changes during Edinger-Westphal
      stimulated accommodation in rhesus monkeys.
AB  - Experiments were undertaken to understand the relationship between dynamic
      accommodative refractive and biometric (lens thickness (LT), anterior chamber
      depth (ACD) and anterior segment length (ASL=ACD+LT)) changes during Edinger
      Westphal stimulated accommodation in rhesus monkeys. Experiments were conducted
      on three rhesus monkeys (aged 11.5, 4.75 and 4.75 years) which had undergone
      prior, bilateral, complete iridectomies and implantation of a stimulating
      electrode in the Edinger-Westphal (EW) nucleus. Accommodative refractive
      responses were first measured dynamically with video-based infrared
      photorefraction and then ocular biometric responses were measured dynamically
      with continuous ultrasound biometry (CUB) during EW stimulation. The same
      stimulus amplitudes were used for the refractive and biometric measurements to
      allow them to be compared. Main sequence relationships (ratio of peak velocity to
      amplitude) were calculated. Dynamic accommodative refractive changes are linearly
      correlated with the biometric changes and accommodative biometric changes in ACD,
      ASL and LT show systematic linear correlations with increasing accommodative
      amplitudes. The relationships are relatively similar for the eyes of the
      different monkeys. Dynamic analysis showed that main sequence relationships for
      both biometry and refraction are linear. Although accommodative refractive
      changes in the eye occur primarily due to changes in lens surface curvature, the
      refractive changes are well correlated with A-scan measured accommodative
      biometric changes. Accommodative changes in ACD, LT and ASL are all well
      correlated over the full extent of the accommodative response.

PMID- 15721618
TI  - A comparison of intravitreal piperacillin/tazobactam with ceftazidime in
      experimental Pseudomonas aeruginosa endophthalmitis.
AB  - In the present study, we aimed at comparing the efficacies of intravitreal
      piperacillin/tazobactam and ceftazidime applications in the treatment of
      experimental Pseudomonasaeruginosa endophthalmitis in rabbit eyes. Twenty-four
      New Zealand white albino rabbits were divided into three groups (n=8 in each),
      and the right eyes received 0.1 ml intravitreal injections of P. aeruginosa
      suspension. The left eyes served as uninfected control and were injected with 0.1
      ml of saline solution. The right eyes of rabbits in group 1 were treated with
      intravitreal injection of 250 microg/0.1 ml piperacillin/tazobactam 24 hr after
      intravitreal inoculation of P. aeruginosa, whereas group 2 eyes received
      intravitreal 1 mg/0.1 ml ceftazidime. Group 3 eyes received no treatment and
      served as infected controls. Clinical, microbiological and histopathological
      evaluations of the eyes in each group were performed on the 1st, 3rd, and 6th day
      after the inoculation of P. aeruginosa. The mean clinical scores of each group
      were similar at the first day after P. aeruginosa inoculation (P>0.05). At the
      6th day, there was no statistically significant difference in mean clinical
      scores between group 1 and 2, but mean clinical score of group 3 was
      significantly higher (P<0.001). Microbiological analysis and histopathological
      scoring demonstrated no statistically significant difference between group 1 and
      2 (for each, P>0.05). Group 3 eyes had a significantly more CFU/ml and higher
      histopathological score (for each, P<0.001). In conclusion, intravitreal
      application of 250 microg/0.1 ml piperacillin/tazobactam seems to be effective in
      the treatment of P. aeruginosa endophthalmitis in rabbits, but is not superior to
      intravitreal ceftazidime application. Therefore, intravitreal
      piperacillin/tazobactam may be a useful alternative to ceftazidime for
      pseudomonal endophthalmitis.

PMID- 15721619
TI  - Quantitative enumeration of vascular smooth muscle cells and endothelial cells
      derived from bone marrow precursors in experimental choroidal neovascularization.
AB  - Choroidal neovascularization (CNV) is characterized by the subretinal invasion of
      a pathologic new vessel complex from the choriocapillaris. Although CNV is
      traditionally considered to consist of endothelial cells, the cellular population
      of CNV is likely more complex in nature, comprising several different cell types.
      In addition, recent studies suggest that the CNV cell population has a dual
      origin (circulating versus resident populations). In this study we sought to
      determine the contribution and origin of different cell types in experimental
      CNV. Laser-induced CNV was performed on chimeric mice generated by reconstituting
      C57BL/6 mice with bone marrow from green fluorescent protein (GFP)-transgenic
      mice. In these mice, bone marrow-derived cells are GFP-labeled.
      Immunofluorescence staining was used to examine both flatmount preparations of
      the choroid and cross sections of the posterior pole for macrophages, endothelial
      cells, vascular smooth muscle cells, retinal pigment epithelial (RPE) cells,
      lymphocytes, or neutrophils at day 3, 7, 14 and 28 post-laser (n=5 per group).
      Cell types present in CNV included macrophages (20% of the cells in CNV),
      endothelial cells (25%), vascular smooth muscle cells (11%), RPE cells (12%) and
      non-labeled cells (32%). The macrophage population was mostly derived from
      circulating monocytes at all timepoints studied (70% were GFP labeled), while
      endothelial and vascular smooth muscle cells were partly bone marrow derived (50
      60% were GFP labeled), and RPE cells appeared to be entirely derived from
      preexisting tissue resident cells. These results demonstrate that bone marrow
      derived progenitor cells contribute significantly to the vascular and
      inflammatory components of CNV. Knowledge of the cellular composition and origin
      might help understand the pathogenic mechanisms controlling CNV severity as well
      as indicate potential targets for therapeutic intervention.

PMID- 15721620
TI  - Differential effects of the EGF family of growth factors on protein secretion,
      MAPK activation, and intracellular calcium concentration in rat lacrimal gland.
AB  - The purpose of this study was to investigate the expression of the EGF family of
      growth factors and EGF receptor subtypes (ErbB1-4) present in lacrimal gland and
      determine the effects of these growth factors on different functions of rat
      lacrimal gland. RT-PCR was used to detect mRNA expression in the lacrimal gland
      of selected members of the EGF family of growth factors, namely EGF, transforming
      growth factor alpha (TGF-alpha), heparin-binding EGF (HB-EGF), and heregulin. The
      presence of ErbB receptors was investigated by immunofluorescence microscopy and
      western blot analysis. The effects of EGF, TGF-alpha, HB-EGF, and heregulin on
      protein secretion from lacrimal gland acini were examined using a fluorescent
      assay for peroxidase, a marker of protein secretion. Fura-2 tetra-acetoxymethyl
      ester was used to measure the effects of the growth factors on intracellular
      [Ca2+] ([Ca2+]i) in acini. MAPK activation in acini by these growth factors was
      also examined by western blot analysis using antibodies specific to
      phosphorylated p42/44 MAPK and total p42 MAPK. Rat lacrimal gland expressed EGF,
      TGF-alpha, HB-EGF, and heregulin mRNA, and all four ErbB receptors were present
      in the lacrimal gland as detected by western blot analyses. ErbB 1 and ErbB2 were
      located in basal and lateral membranes of acinar and ductal cells. The location
      of ErbB3 could not be determined while ErbB4 was found in ductal cells. Heregulin
      (10(-7) m) significantly increased protein secretion in lacrimal gland acini
      whereas all growth factors tested significantly increased [Ca2+]i at 10(-7) m.
      TGF-alpha (10(-9) m), heregulin (10(-7) m), EGF (10(-7) m), and HB-EGF (10(-7) m)
      significantly increased the amount of phosphorylated MAPK in lacrimal gland
      acini. We conclude that all members of the EGF family of growth factors studied
      are synthesised in rat lacrimal gland, could activate all four ErbB receptors
      that are present in this tissue, and differentially activate lacrimal gland
      functions.

PMID- 15721621
TI  - Correlations between neuronal nitric oxide synthase and muscarinic M3/M1
      receptors in the rat retina.
AB  - This study determined the different signal pathways involved in M1/M3 muscarinic
      acetylcholine receptor (mAChR) dependent stimulation of nitric oxide synthase
      (NOS) activity/cyclic GMP (cGMP) production and nNOS mRNA expression in rat
      retina. Exposure of the retina to different concentrations of carbachol caused an
      increase in NOS activity, cGMP production and phosphoinositol (PI) accumulation.
      The increase in NOS activity and cGMP content was blocked by L-NMMA and ODQ,
      respectively. Also, phospholipase C (PLC) and calcium/calmodulin (CaM) inhibition
      prevented the carbachol activation on NOS/cGMP pathways. Both, 4-DAMP and
      pirenzepine but not AF-DX 116 blocked the increase in NOS and cGMP induced by
      carbachol. Carbachol-stimulation of M1/M3 mAChR increased nNOS-mRNA levels
      associated with an increase of endogenous NO and cGMP production. The mechanism
      appears to occur secondarily to stimulation of PIs turnover via PLC. This
      triggers a cascade reaction involving CaM and soluble guanylate cyclase leading
      to NO and cGMP accumulation, that in turn, up regulates nNOS-mRNA gene
      expression. These results give novel insight into the mechanism involved in the
      regulation of nNOS-mRNA levels by mAChR activation of retina.

PMID- 15721622
TI  - DNA microarray analysis of gene expression in iris and ciliary body of rat eyes
      with endotoxin-induced uveitis.
AB  - The purposes of this study are to determine the genes that are up- or down
      regulated in eyes with endotoxin-induced uveitis (EIU) by an oligonucleotide
      microarray system, and to determine the temporal and spatial changes in
      expression of selected genes that show strong up-regulation. EIU was induced by a
      footpad injection of lipopolysaccharide (LPS) in male Lewis rats. The expression
      of genes in the iris-ciliary body (ICB) at 2, 6, 12, and 24 hr after LPS
      injection was determined by oligonucleotide microarray analyses and compared to
      that in control rats. The microarray displayed 9911 genes and expressed sequence
      tags (ESTs). Cluster analysis was performed for highly up-regulated genes.
      Selected genes for cytokines (interleukin (IL)-1 beta and IL-6), chemokines
      (RANTES), and immediate early genes (Jun B, c-Fos, and c-Jun) were also studied
      by real-time polymerase chain reaction (PCR). Immunohistochemical studies were
      performed to localize the protein expression of some immediate early gene
      products. After LPS injection, the expression of 1930 genes were increased or
      decreased over 2-folds compared with normal controls by 24 hr. One hundred and
      seventeen genes were up-regulated over 10-fold, and these were classified into
      five clusters with similar expression pattern. The immediate early genes and
      transcription factors genes were included in one cluster of up-regulated genes
      peaking at 2 hr after the LPS injection. The expressions of cytokines,
      chemokines, and adhesion molecules were highly up-regulated. Real-time PCR
      analyses for selected genes showed similar expression changes as detected by the
      microarray analyses. Jun B immunoreactivity was found in the ICB cells at 3 and 6
      hr after LPS injection. Gene expression changes after LPS injection were profiled
      by using an oligonucleotide microarray system. Our data suggest that the
      immediate early genes, such as Jun B, play an important role in inducing the
      inflammatory-related genes in the ICB.

PMID- 15721623
TI  - Gender and estrogen supplementation increases severity of experimental choroidal
      neovascularization.
AB  - Observational clinical studies suggest that post-menopausal women may be at risk
      for more severe age-related macular degeneration, and that estrogen loss due to
      menopause may contribute. We sought to determine the effect of gender and
      estrogen status on the severity of choroidal neovascularization (CNV) in a mouse
      model for experimental choroidal neovascularization. Laser-induced CNV was
      performed in mice with or without estrogen supplementation. At various times,
      eyes were removed for analysis of severity of CNV lesions or for extraction of
      choroidal mRNA to evaluate iNOS, TNF-alpha, MMP-9, and ER-alpha expression, which
      are molecules relevant to angiogenic processes. Also, splenic macrophages were
      analysed for iNOS to determine the effect of estrogen treatment in vitro.
      Finally, laser-induced CNV was performed in iNOS -/- mice. Our result showed that
      aged female mice had significantly larger CNV than age-matched males. Ovariectomy
      in adult mice did not increase severity, but paradoxically estrogen
      supplementation after ovariectomy did increase CNV severity. More severe CNV were
      associated with a significant decrease in choroidal iNOS mRNA. Splenic
      macrophages from estrogen supplemented mice showed a significant increased in TNF
      alpha mRNA expression (eight fold difference compared to the control) but only a
      mild change in iNOS mRNA levels (2-3 fold difference). In vitro data further
      showed that nitric oxide production in splenic macrophages at different estrogen
      levels was not different from controls. Finally, CNV severity was significantly
      more severe in iNOS -/- mice, compared to iNOS +/+ mice after laser treatment. In
      conclusion, aged female mice developed more severe CNV than do males. Estrogen
      replacement seems to increase severity, possibly by suppressing the upregulation
      of choroidal iNOS and activating macrophages. The putative beneficial or
      detrimental role of estrogen biology in age-related macular degeneration must be
      more carefully evaluated and may vary with the stage of age-related macular
      degeneration (atrophic or neovascular) as well as with the specific target cell
      type (monocytes vs. endothelial cell or vascular smooth muscle cell).

PMID- 15721624
TI  - Dynamic mechanical properties of human lenses.
AB  - The purpose of this study was to determine the shear compliance of human
      crystalline lenses as a function of age and frequency. Dynamic mechanical
      analysis was performed on 39 human lenses, ranging in age from 18 to 90 years,
      within the frequency range of 0.001-30 Hz. The lenses were stored at -70 degrees
      C before being measured. The influence of freezing on the mechanical properties
      was determined using pairs of porcine lenses, with one lens measured directly
      after enucleation and the other after freezing. The measurement method had a
      repeatability standard deviation of 4 and 6% for the storage and loss compliance,
      respectively. The reproducibility standard deviation was 31 and 33% for the
      storage and loss compliance respectively. On average, freezing increased the
      storage compliance by 8% and increased the loss compliance by 32%, both depending
      slightly on age and frequency. The human lenses exhibited a distinct viscoelastic
      behavior. The storage and loss compliance depended strongly on age and decreased
      a factor 1000 over a lifetime. Dynamic mechanical analysis has proven to be a
      successful technique for characterizing the mechanical properties of the human
      crystalline lens. The shear compliance decreases exponentially with age.

PMID- 15721626
TI  - Activated epidermal growth factor receptors in the adult human lens.

PMID- 15721625
TI  - Inhibition of corneal neovascularization by a peroxisome proliferator-activated
      receptor-gamma ligand.
AB  - PURPOSE: To determine the efficacy of the peroxisome proliferator-activated
      receptor gamma agonist, pioglitazone, in inhibiting corneal neovascularization.
      METHODS: Twenty-six adult male Sprague-Dawley rats were randomly divided into
      three groups. Each group received intrastromal polymer micropellets containing
      one of the following: Group 1, no active ingredient (n=10); Group 2, vascular
      endothelial growth factor (VEGF) (n=7); Group 3, VEGF and pioglitazone (n=9).
      Neovascularization was evaluated 7 days after pellet implantation. After systemic
      India ink injection, digital photographs of the eyes were taken. The area and
      density of neovascularization were measured using imaging software. RESULTS: Mean
      area of neovascularization was 0.43+/-0.18 mm2 for Group 1, 2.87+/-0.48 mm2 for
      Group 2 and 2.10+/-0.22 mm2 for Group 3. Statistical analysis showed significant
      differences between Groups 1 and 2 and Groups 1 and 3. There was no significant
      difference between Groups 2 and 3. Mean density of neovascularization was 2.16+/
      0.66 for Group 1, 27.14+/-2.93 for Group 2 and 12.02+/-2.24 for Group 3. All
      comparisons between groups were statistically significant (P<0.01). CONCLUSIONS:
      Pioglitazone is effective in decreasing the density of angiogenesis in a VEGF
      induced neovascular rat cornea model. There is possibility of even greater effect
      with higher doses of the drug. Pioglitazone is a promising drug for the treatment
      of ocular neovascularization.

PMID- 15721627
TI  - Comment on 'Ultrahigh resolution optical coherence tomography of the monkey
      fovea. Identification of retinal sublayers by correlation with semithin histology
      sections' by E.M. Anger et al. [Exp. Eye Res. 78 (2004) 1117-1125].

PMID- 15721629
TI  - Assessment of allele dosage at polymorphic microsatellite loci displaying allelic
      imbalance in tumors by means of quantitative competitive-polymerase chain
      reaction.
AB  - Analysis of allelic imbalance at polymorphic marker loci is usually employed to
      identify chromosomal regions affected by recurrent aberrations in tumor genomes.
      Such regions are likely to harbor genes involved in the onset and/or progression
      of cancer. Although often used to identify regions of loss of heterozygosity
      caused by deletions/rearrangements near tumor suppressor gene loci, allelic
      imbalance can also reflect regional amplification, indicating the presence of
      oncogenes. It is difficult to tell these two situations apart after ordinary
      polymerase chain reaction (PCR), but here we describe a method that distinguishes
      allelic loss from allelic gain. The level of allelic imbalance was determined by
      quantitative PCR (QPCR) in the presence of an internal control DNA that displayed
      a third allele at the locus studied. To validate the efficiency of allele
      quantitation, we analyzed an amplified region in a set of rat fibrosarcomas. In
      four tumor samples with amplification of the Met oncogene, we could show with
      QPCR that there was amplification of one of the alleles at a microsatellite
      marker located close to Met. QPCR may be useful for cancer studies because
      experiments may be predesigned for using either suitable microsatellite markers
      or the abundant and polymorphic poly-A tails of rodent identifier sequences.

PMID- 15721630
TI  - Clonal evolution with inv(11)(p15q22) and NUP98/DDX10 fusion gene in imatinib
      resistant chronic myelogenous leukemia.
AB  - The BCR/ABL tyrosine kinase inhibitor imatinib has shown remarkable efficacy in
      treating patients with chronic myelogenous leukemia (CML). In a small portion of
      patients treated with imatinib, however, the disease may progress to advanced
      stages, frequently accompanied by cytogenetic clonal evolution with the
      appearance of additional chromosomal aberrations besides the Philadelphia
      chromosome. Here we report the appearance of an inv(11)(p15q22) as a clonal
      evolution in a CML patient undergoing treatment with imatinib. Leukemic cells
      from the patient were found to express the fusion transcript of NUP98 and DDX10,
      which is in accordance with previously reported cases of de novo or therapy
      related acute myelogenous leukemia and myelodysplastic syndrome with
      inv(11)(p15q22). Although the patient showed resistance to imatinib with the
      disease rapidly progressing to blast crisis, sequence analysis failed to reveal
      any mutation in the kinase domain of BCR/ABL that would explain the imatinib
      resistance. Furthermore, ex vivo treatment of leukemic cells with imatinib
      significantly reduced tyrosine phosphorylation of CrkL, a target of the BCR/ABL
      kinase. These observations raise a possibility that the NUP98/DDX10 fusion might
      be involved in imatinib resistance as well as in acute transformation of CML.

PMID- 15721631
TI  - Pediatric pancreatoblastoma: histopathologic and cytogenetic characterization of
      tumor and derived cell line.
AB  - Little is known of the molecular events underlying the genesis of
      pancreatoblastoma tumors in the pediatric population. Such studies have been
      limited by the rare nature of the disease, infrequent reports detailing
      cytogenetic alterations, and the lack of availability of cell lines for biologic
      studies. We present the isolation of a cell line from a 14-year-old boy with
      malignant pancreatoblastoma, and its cytogenetic characterization using spectral
      karyotyping and comparative genomic hybridization (CGH). The cytogenetic analysis
      revealed an exceedingly complex cytogenetic karyotype, with 33 aberrant
      chromosomes. CGH revealed multiple regions of chromosomal loss and gain,
      including a region on 8q gained in adult pancreatic cancers, one that frequently
      contains the MYC oncogene.

PMID- 15721632
TI  - Role of multiplex FISH in identifying chromosome involvement in myelodysplastic
      syndromes and acute myeloid leukemias with complex karyotypes: a report on 28
      cases.
AB  - Chromosomal abnormalities are found by conventional cytogenetic (CC) analysis in
      about 50% of myelodysplastic syndromes (MDS) and 70% of acute myeloid leukemias
      (AML). When cytogenetic abnormalities are complex, multiplex fluorescence in situ
      hybridization (M-FISH) can help clarify complex chromosomal abnormalities and
      identify rearrangements with prognostic value or cryptic translocations, which
      could be preliminary steps in identifying new genes. We studied by M-FISH 28
      cases of MDS and AML with complex chromosomal abnormalities, 10 of them were
      therapy-related. M-FISH allowed the characterization of unidentified chromosomal
      material in 26 cases (93%). One or several unbalanced rearrangements were
      observed in 27 cases (96%), generally interpreted as deletions or additional
      material by CC. Among those translocations, 4 involved 3 chromosomes. Eighteen
      cryptic translocations undetected by CC were found in 13 cases. By FISH analysis
      using locus specific probes, TP53 deletion, additional copies of MLL, and
      additional copies or deletions of RUNX1/AML1 were observed in 16, 4, and 3 cases,
      respectively. Thus, M-FISH is an important tool to characterize complex
      chromosomal abnormalities which identified unbalanced and cryptic translocations
      in 96% and 46% of the cases studied, respectively. Complementary FISH helped us
      identify involvement of TP53, MLL, and RUNX1/AML1 genes in 82% of cases,
      confirming their probable role in leukemogenesis.

PMID- 15721633
TI  - Chromosome mechanisms and INI1 inactivation in human and mouse rhabdoid tumors.
AB  - The human rhabdoid tumorigenesis orchestrated by INI1 inactivation is associated
      with specific rearrangements of chromosome 22 that correlate with preferential
      anatomic tumor locations. A literature review revealed significant correlations
      between an apparently normal karyotype and kidney tumors, monosomy 22 and
      cerebral tumors, and chromosome 22 translocations and tumors at other anatomic
      sites. In the mouse rhabdoid tumor model, specifically in the four tumors that we
      tested for loss of heterozygosity, neither partial deletion nor monosomy of
      chromosome 10 could be detected. In contrast to the human data, the only
      chromosome mechanism involved in the 18 mouse tumors studied appears to be a
      mitotic recombination or a nondisjunction-duplication. Additionally, and despite
      mouse tumor incidence across a variety of sites, no rhabdoid tumor could be
      observed in the mouse kidney. These data suggest that the chromosome mechanisms
      for INI1 inactivation and the selective cell survival pressure differ in human
      and mouse.

PMID- 15721634
TI  - Molecular cytogenetic characterization of rearrangements involving 12p in
      leukemia.
AB  - Translocations involving the short arm of chromosome 12 are frequent events among
      patients with various hematologic malignancies. In approximately half of these
      patients, fluorescence in situ hybridization (FISH) analysis has shown that the
      breakpoints are clustered within the ETS-variant gene 6 (ETV6) at 12p13, leading
      to its fusion with a variety of partner genes on different chromosomes. The
      remaining patients have breakpoints centromeric or telomeric to ETV6 or, less
      frequently, interstitial 12p13 deletions that invariably involve this gene. In
      most cases reported, 12p translocations were found to be associated with other
      structural and/or numerical abnormalities as part of a complex karyotype.
      Initially using conventional cytogenetic analysis, we characterized the
      chromosomal breakpoints of three leukemia patients (two with B-acute
      lymphoblastic leukemia and one with myelodysplastic/myeloproliferative disorder)
      presenting a t(5;12)(q13;p13), t(12;15)(p13;q22), and dic(9;12)(p11;p11),
      respectively, as the only structural abnormalities in the karyotype. These
      rearrangements were further investigated using FISH and molecular studies. Two
      cases revealed cryptic three-way translocations that had gone undetected in the
      conventional cytogenetic analyses. One of the cases presented an ETV6
      rearrangement with an unsuspected fusion, with the CBFA2 gene at 21q22. In the
      other two, small and large 12p deletions that included ETV6 were found. This
      report illustrates the chromosomal and molecular heterogeneity of rearrangements
      underlying 12p chromosome translocations in leukemia.

PMID- 15721635
TI  - Conventional and array-based comparative genomic hybridization analysis of
      nasopharyngeal carcinomas from the Mediterranean area.
AB  - Nasopharyngeal carcinoma (NPC) occurs with a high incidence in Southeast Asia and
      to a lesser extent in the Mediterranean area, especially in Tunisia, Algeria, and
      Morocco. Cellular gene alterations combined with latent Epstein-Barr virus
      infection are thought to be essential for NPC oncogenesis. To date, chromosome
      analysis with comparative genomic hybridization (CGH) has been reported
      exclusively for NPCs from Southeast Asia. Although NPCs from the Mediterranean
      area have several distinct clinical and epidemiological features, CGH
      investigations have been lacking. Chromosome analysis was therefore undertaken on
      a series of NPC xenografts and biopsies derived from patients of Mediterranean
      origin. Four xenografts were investigated with a combination of conventional CGH,
      array-based CGH, and comparative expressed sequence hybridization. In addition,
      23 fresh NPC biopsies were analyzed with conventional CGH. Data obtained from
      xenografts and fresh biopsies were consistent, except that amplification of genes
      at 18p was observed only in xenografts derived from metastatic tissues. Frequent
      gains associated with gene overexpression were detected at 1q25 approximately
      qter (64%) and 12p13 (50%). Losses were noticed mainly at 11q14 approximately q23
      (50%), 13q12 approximately q31 (50%), 14q24 approximately q31 (43%), and 3p13
      approximately p23 (43%). Comparison with previous reports suggests that
      Mediterranean NPCs have higher frequencies of gains at 1q and losses at 13q than
      their Asian counterparts.

PMID- 15721636
TI  - Primary myeloid sarcoma of the testicle with t(15;17).
AB  - The first case of acute promyelocytic leukemia presenting as a solitary
      testicular mass (myeloid sarcoma) that relapsed in the contralateral testicle is
      described. The neoplastic cells strongly expressed chloroacetate esterase,
      myeloperoxidase, CD33, CD43, and weakly, CD117. The presence of many azurophil
      granules and Auer rods was detected by electron microscopy. Translocation
      (15;17)(q22;q21.1) was revealed by cytogenetics and was verified by fluorescence
      in situ hybridization. Contralateral testicle is a favorite site for recurrence
      in a subset of testicular myeloid sarcomas. Subclassification of all cases of
      myeloid sarcoma ought to be attempted.

PMID- 15721637
TI  - NUP98 is fused to HOXA9 in a variant complex t(7;11;13;17) in a patient with AML
      M2.
AB  - The t(7;11)(p15;p15.4) has been reported to fuse the NUP98 gene (11p15), a
      component of the nuclear pore complex, with the class-1 homeobox gene HOXA9 at
      7p15. This translocation has been associated with myeloid leukemias,
      predominantly acute myeloid leukemia (AML) M2 subtype with trilineage
      myelodysplastic features, and with a poor prognosis. The derived fusion protein
      retains the FG repeat motif of NUP98 N-terminus and the homeodomain shared by the
      HOX genes, acting as an oncogenic transcription factor critical for
      leukemogenesis. We report here a new complex t(7;11)-variant, i.e.,
      t(7;11;13;17)(p15;p15;p?;p1?2) in a patient with AML-M2 and poor prognosis. The
      NUP98-HOXA9 fusion transcript was detected by RT-PCR, suggesting its role in the
      malignant transformation as it has been postulated for other t(7;11)-associated
      leukemias. No other fusion transcripts involving the NUP98 or HOXA9 genes were
      present, although other mechanisms involving several genes on chromosomes 13 and
      17 may also be involved. To our knowledge, this is the first t(7;11) variant
      involving NUP98 described in hematological malignancies.

PMID- 15721639
TI  - A clonal dic(16;21)(p13.1;p11.2)del(16)(q11.1), with gains of several chromosomes
      and monosomy 21, in a case of splenic hamartoma: evidence for its neoplastic, not
      hamartomatous, origin.
AB  - Cytogenetic examination of a case of splenic hamartoma led to the discovery of a
      clonal population with the karyotype 47 approximately
      58,XX,+X,+4,+5,+5,+6,+10,+12,+14,der(16)dic(16;21)(p13.3;p11.2),
      dic(16;21)del(16)(q11.1),+17,+19,+20,-21. This finding is indicative of a
      neoplastic, not hamartomatous, origin for this lesion.

PMID- 15721638
TI  - Jumping translocation of 1q in a BCR/ABL-positive acute lymphoblastic leukemia.
AB  - Jumping translocations (JT) are rare chromosomal abnormalities in which an
      identical copy of a chromosomal region (donor) is translocated to a different
      chromosome (acceptor). Chromosome 1 is often involved as donor chromosome. JTs of
      the long arm of chromosome 1 (1q) or parts of it are associated with a poor
      outcome. We report on a 72-year-old male patient with a BCR/ABL1 rearrangement
      positive acute lymphoblastic leukemia (common ALL, or c-ALL; FAB L2 morphology)
      and with additional structural and numeric aberrations. Four aberrant clones were
      observed after conventional cytogenetic analysis. Three of the four clones showed
      a JT with 1q as donor and 3q, 8q, and 22q as acceptors. To the best of our
      knowledge, neither JT between 1q and chromosome 3 nor JT between 1q and
      chromosome 22 have been described in c-ALL. This report emphasizes the frequent
      involvement of 1q in JT and the association with a poor prognosis.

PMID- 15721640
TI  - A der(19)t(12;19)(q12;p13.3) in a case of pediatric acute leukemia with unusual
      immunophenotype.
AB  - We describe a case of acute leukemia in a child with an unusual immunophenotype
      and a novel cytogenetic abnormality. The leukemia blasts expressed myeloid,
      natural killer and B-lineage associated antigens. Cytogenetics showed the
      presence of a novel unbalanced chromosomal translocation,
      der(19)t(12;19)(q12;p13.3). The patient achieved and maintained remission with
      myeloid-directed chemotherapy. The differential diagnosis of the immunophenotype
      and the potential fusion genes are discussed.

PMID- 15721641
TI  - Rearrangement of the MLL gene in acute myeloblastic leukemia: report of two rare
      translocations.
AB  - Band 11q23 is known to be involved in translocations and insertions with a
      variety of partner chromosomes. They lead to MLL rearrangement, resulting in a
      fusion with numerous genes. We report here 2 male adults in whom a diagnosis of
      acute myelomonoblastic leukemia (FAB M4) and acute monoblastic leukemia (FAB M5)
      was made. Conventional cytogenetic techniques showed a 45,XY,t(1;11)(p32;q23),-7
      karyotype in the first case and a 46,XY, t(11;17)(q23;q21) in the second case.
      Fluorescent in situ hybridization (FISH) with a specific MLL probe showed the
      gene to be disrupted, the 3' region being translocated on the derivative
      chromosomes 1 and 17, respectively. Fourteen and 24 patients, including ours,
      with acute myeloblastic leukemia associated with a t(1;11)(p32;q23) and a
      t(11;17)(q23;q21), respectively have been reported in the literature. Several
      patients with the latter translocation have also been identified to have acute
      lymphoblastic leukemia (ALL). Although both translocations are preferentially
      associated with monocytic differentiation, the t(11;17)(q23;q21) is more common
      in adults and has been reported in many patients with ALL, compared to the
      t(1;11)(p32;q23).

PMID- 15721642
TI  - A complex translocation (9;22;16)(q34;q11.2;p13) in chronic myelocytic leukemia.
AB  - The t(9;22) is present in almost all cases with chronic myelocytic leukemia
      (CML). Around 5% of these patients show complex translocations involving a third
      chromosome in addition to chromosomes 9 and 22. All chromosomes have participated
      in these variants and the BCR-ABL1 hybrid gene is always present. We describe a
      CML case with a new complex t(9;22;16)(q34;q11.2;p13). Seven months after
      imatinib treatment a karyotype showed the appearance of a clone with a standard
      t(9;22) in addition to the clone with the complex translocation. The b3a2
      transcript of BCR-ABL1 was detected both at diagnosis and 7 months after therapy.
      In CML, both complex translocations and standard translocations have the same
      prognosis. However, these complex variants could contribute to the tumoral
      evolution by conferring selective advantages that, in turn, cause the
      preferential manifestation at diagnosis of clones with complex translocations.

PMID- 15721643
TI  - Cryptic 5' MLL gene insertion in an X-chromosome in acute myeloblastic leukemia.
AB  - Band 11q23 is known to be involved in translocations and insertions with a
      variety of partner chromosomes. They lead to MLL rearrangement, resulting in
      fusion with numerous genes. We report here on a 43-year-old man presenting with
      asthenia and pancytopenia who was diagnosed with acute myeloblastic leukemia FAB
      M5. Conventional cytogenetic techniques showed a del(11)(q21). Using a specific
      probe for fluorescent in situ hybridization, the MLL gene was found to be
      disrupted, with the 5' region being inserted into the X-chromosome (around bands
      q24 approximately q25), as confirmed by whole X-chromosome painting. The
      accumulating data on acute myeloblastic leukemia demonstrate that the 5'-MLL
      insertion in an X-chromosome is a rare but recurrent abnormality associated with
      leukemia, not only in infants, but also in adults.

PMID- 15721644
TI  - Analysis of somatic NF1 promoter methylation in plexiform neurofibromas and
      Schwann cells.
AB  - Neurofibromatosis 1 (NF1) is an autosomal dominant disorder with the
      characteristic feature being the neurofibroma. It is believed that both NF1
      alleles must be inactivated as the first step in tumorigenesis. However, often
      the somatic mutations are not identified, suggesting that epigenetic changes such
      as methylation could account for the "second hit" in some tumors. The literature
      reports that the region of the NF1 promoter surrounding the transcription start
      site is completely unmethylated in several normal tissues and some NF1-related
      dermal and plexiform neurofibromas. We analyzed the methylation state of the NF1
      promoter in normal Schwann cells (the cell type clonally expanded in
      neurofibromas) and in NF1-related plexiform tumor samples with unidentified
      somatic mutations. In a region of 451 bp surrounding the transcription start
      site, a low level of methylation was found at several specific cytosines in 12 of
      18 tumor samples. Overall, epigenetic silencing through methylation does not
      appear to be a major mechanism for the second hit. However, this study, which
      analyzed the largest number of NF1-related plexiform tumors and is the first to
      include Schwann cell-enriched tumor cultures, detected greater methylation than
      in any previous reports. This suggests that methylation, especially at potential
      transcription factor binding sites, is moderately perturbed in some plexiform
      neurofibromas and should be investigated further.

PMID- 15721645
TI  - A second case of myelodysplastic syndrome with t(9;12)(q22;p12).

PMID- 15721646
TI  - Standard mono- and dinucleotide repeats do not appear to be sensitive markers of
      microsatellite instability in the Ewing family of tumors.

PMID- 15721647
TI  - Prenatal diagnosis history of a Li-Fraumeni syndrome family.

PMID- 15721648
TI  - Real-time deformable models for surgery simulation: a survey.
AB  - Simulating the behaviour of elastic objects in real time is one of the current
      objectives of computer graphics. One of its fields of application lies in virtual
      reality, mainly in surgery simulation systems. In computer graphics, the models
      used for the construction of objects with deformable behaviour are known as
      deformable models. These have two conflicting characteristics: interactivity and
      motion realism. The different deformable models developed to date have promoted
      only one of these (usually interactivity) to the detriment of the other
      (biomechanical realism). In this paper, we present a classification of the
      different deformable models that have been developed. We present the advantages
      and disadvantages of each one. Finally, we make a comparison of deformable models
      and perform an evaluation of the state of the art and the future of deformable
      models.

PMID- 15721649
TI  - A resampling approach for adjustment in prediction models for covariate
      measurement error.
AB  - Recent works on covariate measurement errors focus on the possible biases in
      model coefficient estimates. Usually, measurement error in a covariate tends to
      attenuate the coefficient estimate for the covariate, i.e., a bias toward the
      null occurs. Measurement error in another confounding or interacting variable
      typically results in incomplete adjustment for that variable. Hence, the
      coefficient for the covariate of interest may be biased either toward or away
      from the null. This paper presents a new method based on a resampling technique
      to deal with covariate measurement errors in the context of prediction modeling.
      Prediction accuracy is our primary parameter of interest. Prediction accuracy of
      a model is defined as the success rate of prediction when the model predicts new
      response. We call our method bootstrap regression calibration (BRC). We study
      logistic regression with interacting covariates as our prediction model. We
      measure the prediction accuracy of a model by receiver operating characteristic
      (ROC) method. Results from simulations show that bootstrap regression calibration
      offers consistent enhancement over the commonly used regression calibration (RC)
      method in terms of improving prediction accuracy of the model and reducing bias
      in the estimated coefficients.

PMID- 15721650
TI  - An alternative method for electrophoretic gel image analysis in the GelMaster
      software.
AB  - A novel methodology of electrophoretic gel image analysis has been proposed that
      is based on two-dimensional image processing methods instead of previously used
      one-dimensional Gaussian deconvolution. The crucial problem of the analysis of
      imperfect gels, that consists in band detection, is solved using the algorithms
      of band boundary detection and intensity homogeneity indication. The template
      approach represents the core element of the developed algorithms. The GelMaster
      software system has been developed in which the novel algorithms are implemented.
      It involves two-stage interaction with the user: detection of the true bands and
      deleting the false band detections. The main features of the GelMaster system and
      the most important algorithms are described.

PMID- 15721651
TI  - Fractal analysis of acceleration signals from patients with CPPD, rheumatoid
      arthritis, and spondyloarthroparthy of the finger joint.
AB  - Arthritis is one of the leading causes of disability and affects a major segment
      of the population. Consequently, accurate diagnosis of arthritis is important.
      Arthritis due to calcium pyrophosphate deposition disease (CPPD), rheumatoid
      arthritis, and spondyloarthropathy, induce complex changes in the cartilage and
      the articular surface. The fractal dimension provides a measure of the complexity
      of a signal. Recently, we have developed non-invasive acceleration measurements
      to characterize the arthritic patients. The question remains if the fractal
      dimension of the acceleration signal is different for different arthritis
      conditions. The purpose of this study was to distinguish between different types
      of arthritis of the finger joint using the fractal dimension of the acceleration
      signal obtained from the finger joint of the arthritic patients. Acceleration
      signals were obtained from the finger joint of arthritis patients with rheumatoid
      arthritis, spondyloarthropathy, and calcium pyrophosphate deposition disease of
      the finger joint. ANOVA results showed that there were significant differences
      between the fractal dimension of acceleration signals from patients having
      calcium pyrophosphate deposition disease and rheumatoid arthritis and
      spondyloarthropathy. Fractal dimension of acceleration signals, in concert with
      other clinical symptoms, can be used to classify different types of arthritis.

PMID- 15721652
TI  - Lead field computation for the electrocardiographic inverse problem--finite
      elements versus boundary elements.
AB  - In order to be able to solve the inverse problem of electrocardiography, the lead
      field matrix (transfer matrix) has to be calculated. The two methods applied for
      computing this matrix, which are compared in this study, are the boundary element
      method (BEM) and the finite element method (FEM). The performance of both methods
      using a spherical model was investigated. For a comparable discretization level,
      the BEM yields smaller relative errors compared to analytical solutions. The BEM
      needs less computation time, but a larger amount of memory. Inversely calculated
      myocardial activation times using either the FEM or BEM computed lead field
      matrices give similar activation time patterns. The FEM, however, is also capable
      of considering anisotropic conductivities. This property might have an impact for
      future development, when also individual myocardial fiber architecture can be
      considered in the inverse formulation.

PMID- 15721653
TI  - Hardness and yield strength of dentin from simulated nano-indentation tests.
AB  - The finite element method (FEM) is applied for studying the hardness (H) and
      yield strength (Y) of dentin subjected to a nano-indentation process. The nano
      indentation experiments were simulated with the ABAQUS finite element software
      package. This test, performed with a spherical indenter, was simulated by
      axisymmetric finite element analysis. The load versus displacement was calculated
      during loading-unloading sequence for different elastic modulus (E) and yield
      strength. Hardness and maximum principal compressive and tensile stresses were
      plotted for different elastic modulus depending on yield strength. The dentin was
      assumed to be isotropic, homogenous and elasto-plastic. The theoretical results
      outlined in this study were compared with the experimental works reported in the
      literature and then hardness and yield strength of dentin was estimated.

PMID- 15721654
TI  - Integral-based parameter identification for long-term dynamic verification of a
      glucose-insulin system model.
AB  - Hyperglycaemia in critically ill patients increases the risk of further
      complications and mortality. This paper introduces a model capable of capturing
      the essential glucose and insulin kinetics in patients from retrospective data
      gathered in an intensive care unit (ICU). The model uses two time-varying patient
      specific parameters for glucose effectiveness and insulin sensitivity. The model
      is mathematically reformulated in terms of integrals to enable a novel method for
      identification of patient specific parameters. The method was tested on long-term
      blood glucose recordings from 17 ICU patients, producing 4% average error, which
      is within the sensor error. One-hour forward predictions of blood glucose data
      proved acceptable with an error of 2-11%. All identified parameter values were
      within reported physiological ranges. The parameter identification method is more
      accurate and significantly faster computationally than commonly used non-linear,
      non-convex methods. These results verify the model's ability to capture long-term
      observed glucose-insulin dynamics in hyperglycemic ICU patients, as well as the
      fitting method developed. Applications of the model and parameter identification
      method for automated control of blood glucose and medical decision support are
      discussed.

PMID- 15721655
TI  - Predicting time of parturition from changing vaginal temperature measured by data
      logging apparatus in beef cows with twin fetuses.
AB  - Vaginal temperatures (VT) of crossbred (Japanese Black crossed Holstein-Friesian)
      beef cows (n = 31) were measured by a data-logging apparatus to obtain serial
      data from days 0 to 6 before parturition. For both single and twin pregnancies,
      no significant differences were observed in VT during days 3-6 before
      parturition. Maternal VT was not affected by maternal weight just after
      parturition, parity, fetal sex, or total fetal litter weight. Average of twin
      litter weights for two males (MM) and two females (FF) had the strong positive
      correlations (r = 0.84; P < 0.05) with maternal VT, whereas twin weights of mixed
      gender twins (FM) did not correlate with maternal VT (r = -0.26; P = 0.61).
      Maternal temperature decreased as weights of the female fetus of FM twins became
      heavier (r = -0.82; P < 0.05). In contrast, maternal VT of FF and MM twins
      increased as twin weights increased. We defined when the VT began to decrease
      before parturition by two different methods. One was the "same hours method"
      where differences in VT between a particular time of day and the corresponding
      time of the preceding day were compared when the VT was consistently > or =0.3 or
      > or =0.5 degrees C for more than 3h. The second method was the "maximum-minimum
      method" where decreased in the maximum or the minimum values of the day over > or
      =0.3 and > or =0.5 degrees C were compared to values of preceding day. Onset of
      decreased VT before expulsion was not different between singletons and twins. In
      an attempt to define the critical condition in predicting parturition, we
      estimated assumable predicting probability using the 31 cows that were collected
      VT. When the parturition occurred within 60 h in the "same hours method" and 72 h
      since VT was > or =0.3 degrees C and in the "maximum-minimum method", the
      assumable probability was 100%. In verification experiment under these condition,
      the "same hours method" had a higher probability of predicting the time of
      parturition than the "maximum-minimum method", and it was possible to detect the
      onset of decreased VT at the correct time by the minutes. We concluded that "same
      hours method" was useful for predicting parturition time in cattle with single
      and twin pregnancies by the serial measurement of vaginal temperature.

PMID- 15721656
TI  - Ovum pick up and in vitro embryo production in cows superstimulated with an
      individually adapted superstimulation protocol.
AB  - The aim of this experiment was to apply an ovarian superstimulation protocol
      prior to ovum pick up (OPU), tailored to the individual donor response, to
      evaluate its advantages and disadvantages in terms of follicle numbers and
      diameters, the numbers of retrieved oocytes and day 7 cultured blastocysts. Ten
      adult non-lactating dairy cows were superstimulated with pFSH and subjected to
      ovum pick up-in vitro fertilisation (OPU-IVF) 6 times at 2-week intervals. On day
      0 of each 2-week period, all follicles >8mm were ablated and an ear implant
      (Crestar, Intervet, Belgium) was inserted. On day 2, 48 h after follicle ablation
      the animals were administered six equal doses of pFSH, divided into morning and
      evening doses for 3 days. On day 7, 48 h following the last pFSH injection,
      follicle diameters were measured by ultrasound and all follicles were subjected
      to OPU. All cumulus-oocyte complexes (COC), regardless of their quality, were
      subjected to in vitro maturation-in vitro fertilisation-in vitro culture (IVM-IVF
      IVC). The total dose of pFSH prior to the first OPU session was 300 microg per
      animal. During the following OPU sessions, the total pFSH dose was either kept
      unchanged, increased or reduced (+/-50 microg), according to the percentage of
      follicles of more than 11 mm in diameter, present in the previous session of that
      particular donor. The mean number of punctured follicles per session was 11.9 +/-
      7.7 (mean +/- S.D.), with 16% of follicles exceeding 11 mm. These follicles
      yielded a mean of 5.6 +/- 4.1 cumulus oocyte complexes (COC), 32% of which had
      >/=3 layers of cumulus cells (quality 1 and 2). The recovery rate was 47%.
      Finally, all COC were subjected to IVM-IVF-IVC, which resulted in a mean of 2.0
      +/- 2.3 blastocysts on day 7 postinsemination. The subtle changes in pFSH dose
      influenced the sizes but not the numbers of follicles, the latter parameter was
      influenced by the individual donor and the OPU session.

PMID- 15721657
TI  - Fertility of cryopreserved sperm in three bulls with different Robertsonian
      translocations.
AB  - The fertility of three bulls carrying different Robertsonian translocations
      (rob(1;29), rob(14;17) and rob(26;29)) was evaluated. Oocytes-cumulus complexes
      obtained from slaughterhouse-derived ovaries were matured and then fertilised in
      vitro with frozen/thawed seminal material from the above mentioned subjects, and
      from control bulls with normal karyotype. An assessment was first made of the
      concentration, vitality and acrosome integrity of the seminal material to be sure
      that possible differences in the results of the in vitro fertilisation
      experiments were not due to seminal material quality. The results of the
      experiments, evaluated by the percentage of cleaved embryos and blastocysts per
      cleaved embryo, indicated that the three bulls carrying Robertsonian
      translocations had similar fertilising power and semen qualitative parameters to
      the controls. These data suggest that neither gametogenesys impairment nor
      decreased spermatozoa fertilising capacity is responsible for the reduced
      fertility in bulls with Robertsonian translocations. What the data do confirm is
      that the observed in vivo hypofertility for karyologically abnormal bulls is
      mainly due to early embryonic mortality.

PMID- 15721658
TI  - Effects of oestradiol and some of its esters on gonadotrophin release and ovarian
      follicular dynamics in CIDR-treated beef cattle.
AB  - Three experiments were conducted to: (1) compare the effect of three oestradiol
      formulations on gonadotrophin release in ovariectomised cows; (2) compare the
      effects of either oestradiol-17beta (E-17beta) or oestradiol benzoate (EB), given
      at two doses, on the synchrony of ovarian follicular wave emergence in CIDR
      treated beef cattle; and (3) determine the timing of ovulation of the dominant
      follicle of a synchronised follicular wave following administration of E-17beta
      or EB 24h after progesterone withdrawal. In Experiment 1, ovariectomised cows (n
      = 16) received a once-used CIDR on Day 0 (beginning of the experiment) and were
      allocated randomly to receive 5mg of E-17beta, EB or oestradiol valerate (EV)
      plus 100mg progesterone i.m. The CIDR inserts were removed on Day 7. There were
      effects of time, and a treatment-by-time interaction (P < 0.0001) for plasma
      concentrations of both oestradiol and FSH. Plasma oestradiol concentrations
      peaked 12h after treatment, with highest (P < 0.01) peak concentrations in cows
      given E-17beta; estradiol concentrations subsequently returned to baseline by 36
      h in E-17beta-treated cows and by 96 h in EB- and EV-treated cows. Plasma FSH
      concentrations decreased by 12h after oestradiol treatment in all groups (P <
      0.0001), reached a nadir at 24h, and increased by 60 h in all groups; plasma FSH
      reached higher (P < 0.02) concentrations in E-17beta-treated than in EB- or EV
      treated cows. In Experiment 2, non-lactating Hereford cows (n = 29) received a
      new CIDR on Day 0 (beginning of the experiment), and were assigned randomly to
      receive 1 or 5mg of E-17beta or EB i.m. on Day 1. On Day 8, CIDR were removed and
      PGF was given. Transrectal ultrasonography was done once daily from 2 days before
      CIDR insertion to 2 days after CIDR removal, and then twice-daily to ovulation.
      Although there was no difference among groups in the interval from oestradiol
      treatment to follicular wave emergence (4.2 +/- 0.3 days; P = 0.5), 5mg of E
      17beta resulted in the least variable interval to wave emergence (P < 0.005),
      compared with the other treatment groups which were not different (P = 0.1). For
      the interval from CIDR removal to ovulation, there were no differences among
      groups for either means (P = 0.5) or variances (P = 0.1). In Experiment 3, beef
      heifers (n = 32) received a once-used CIDR on Day 0 (beginning of the experiment)
      plus 100mg progesterone i.m. and were assigned randomly to receive 5mg E-17beta
      or 1mg EB i.m. On Day 7, CIDR were removed and all heifers received PGF. On Day 8
      (24h after CIDR removal), each group was subdivided randomly to receive 1mg of
      either E-17beta or EB i.m. There was no effect of oestradiol formulation on
      interval from treatment to follicular wave emergence (4.1 +/- 0.2 days; P = 0.7)
      or on the median interval (76.6h; P = 0.7) or range (72-120 h; P = 0.08) from
      CIDR removal to ovulation. In summary, oestradiol treatments suppressed FSH in
      ovariectomised cows, with the duration of suppression dependent on the oestradiol
      formulation. Both E-17beta and EB effectively synchronised ovarian follicular
      wave emergence and ovulation in CIDR-treated cattle, and the interval from CIDR
      removal to ovulation did not differ in heifers given either E-17beta or EB 24h
      after CIDR removal.

PMID- 15721659
TI  - Pattern of circulating luteinizing hormone isoforms during the estrous and luteal
      phases in Holstein heifers.
AB  - The pattern of distribution of circulating luteinizing hormone (LH) isoforms in
      cattle during estrus and the luteal phase was investigated. In each stage, the
      stage of the estrous cycle was synchronized in seven Holstein heifers with a
      prostaglandin analogue. After estrus was detected, blood samples were taken at 2
      h intervals for 24h. In the luteal phase, animals received 250 microg i.v. of
      GnRH and blood samples were collected every 15 min for 5h. LH concentration in
      the samples was determined. Samples with the greatest LH concentration in estrus
      (pre-ovulatory peak) and those collected 60 min after GnRH administration (luteal
      phase) were analyzed by chromatofocusing, eluted with a pH gradient from 10.5 to
      3.5. Eluted LH was grouped into basic (pH > or = 7.5), neutral (pH 7.4-6.5) and
      acidic isoforms (pH < or = 6.4) as well as by pH unit. In both phases, basic
      forms were the most abundant, and these were greater (P < 0.05) during the luteal
      phase (78.4 +/- 4.2%) as compared with during estrus (57.1 +/- 6.2%); the
      proportion of neutral and acidic isoforms in estrus (13.7 +/- 2.6%; 28.5 +/-
      2.8%) was greater (P < 0.05) as compared with the luteal phase (3.0 +/- 0.7; 18.7
      +/- 3.4). These results indicate that the relative proportion of LH isoforms
      secreted by the adenohypophysis differ by stage of estrous cycle. The addition of
      excess of NaCl to the column modifies the antigen-antibody binding in the RIA,
      and the proteins eluted are erroneously quantified as LH; this is an artifact of
      the technique.

PMID- 15721660
TI  - Detection of Fas ligand in the bovine oviduct.
AB  - Presence of a Fas-Fas ligand (FasL) system defines the immune-privileged status
      of certain tissues such as placenta. This study examined the fluids and tissue(s)
      of the bovine oviduct, where both spermatozoa and early embryos escape
      elimination by the female immune system, for the presence and the distribution of
      Fas and FasL, which might provide an explanation for the immune-privileged site
      of this organ. In the present study, the immunolocalisation of FasL and Fas, as
      well as the gene expression of FasL, were determined in the uterotubal junction
      (UTJ), isthmic (I) and ampullar (A) segments of the oviduct during oestrus and
      the luteal phase of the oestrous cycle. The degree of apoptosis of oviductal
      epithelium was examined by the TUNEL method. Oviductal fluid (ODF), collected
      chronically via indwelling catheters from the I or A segments during both non
      luteal and luteal phases of the cycle, was analysed for the presence of FasL. The
      Fas immunostaining was scattered along the epithelium of all regions of the
      oviduct and cycle stages investigated, whereas FasL immunolabelling was more
      conspicuous in oestrous samples. This staining disappeared during the luteal
      phase, which was particularly evident in the sperm reservoir (UTJ and I). There
      were fewer TUNEL-positive cells than Fas- or FasL-positive cells in the oviductal
      epithelium, suggesting that tubal Fas and FasL are not directly involved in
      epithelial apoptosis. Western blot analyses detected FasL in ODF collected from
      both I and A, most conspicuously as a 24-27kDa band but also at a 40-45kDa band
      level. FasL mRNA was expressed in the epithelial cells from the sperm reservoir
      and A during both non-luteal and luteal phases. However, the level of expression
      differed significantly between segments during the luteal phase. The results
      provide novel evidence that the Fas-FasL system is present in the bovine oviduct
      and could be involved in mediating survival of spermatozoa and early embryos.

PMID- 15721662
TI  - Effect of cervical and vaginal insemination with liquid semen stored at room
      temperature on fertility of goats.
AB  - The effect of vaginal and cervical deposition of liquid semen stored at room
      temperature on the fertility of goats was tested in a field trial in which 217
      Norwegian Dairy goats aged between 6 months and 7.5 years from 14 farms were
      inseminated after natural oestrous. Cervical insemination with 200 x 10(6)
      spermatozoa resulted in 25-day non-return and kidding rates of 87.0 and 78.0%,
      and vaginal insemination gave 85.5 and 74.3%, respectively. There was no
      significant difference between the cervical and vaginal inseminations (P = 0.59
      for the 25-day non-return and P = 0.40 for the kidding rates). Farm had a
      significant effect on the 25-day non-return rate (P = 0.03) but not on the
      kidding rate (P = 0.07). There were no significant differences between the
      fertility rates for different bucks (P = 0.36 for the 25-day non-return and P =
      0.15 for the kidding rates). Fertility results after vaginal insemination were
      encouragingly high. Vaginal insemination is a simple, less costly and time
      consuming technique compared to others, also bringing into focus the animal
      welfare aspects of the artificial insemination procedure. As the final goal is to
      establish a technique that could be applied similarly on a large scale by all
      farmers, vaginal insemination must be considered as a method that would simplify
      the use of liquid buck semen in Norway.

PMID- 15721661
TI  - Evaluation of single intratesticular injection of calcium chloride for
      nonsurgical sterilization of male Black Bengal goats (Capra hircus): a dose
      dependent study.
AB  - This study describes the induction of chemosterilization in three groups each of
      six adult male Black Bengal goats at 30 days after a single bilateral
      intratesticular injection of a calcium chloride (CaCl(2), 2H(2)O) solution at the
      doses of 10, 20 or 40 mg/kg body weight/testis, always in a 2 ml volume of normal
      saline. Another one group of animals received only 2 ml of normal saline per
      testis as a control. The induction of chemosterilization was measured using
      relative testicular weight as well as histomorphological parameters including
      seminiferous tubular architecture and germ cell association in seminiferous
      tubules along with morphology of the interstitial space. Biochemical markers
      included activities of testicular Delta(5), 3beta-hydroxysteroid dehydrogenase
      (Delta(5), 3beta-HSD), 17beta-hydroxysteroid dehydrogenase (17beta-HSD),
      catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST) and
      superoxide dismutase (SOD) as well as monitoring the level of testicular
      thiobarbituric acid reactive substances (TBARS), conjugated dienes and reduced
      glutathione (GSH) content along with plasma concentrations of testosterone, LH
      and FSH. Histomorphological measures of testes showed total necrosis of
      testicular tissue at 30 days after an injection of either 20 or 40 mg CaCl(2)
      along with fibrosis in seminiferous tubules and interstitial spaces. Infiltration
      of leucocytes was observed with the 40 mg dose. Disintegration of germ cell
      arrangement in seminiferous tubules and washing out of germ cells from the
      tubules were noted with the 10mg dose. Relative organ weights, plasma
      concentrations of testosterone, testicular activities of Delta(5), 3beta-HSD,
      17beta-HSD, catalase, GPx, GST, and SOD and testicular contents of GSH all were
      declined. Increases occurred in testicular TBARS, conjugated dienes and plasma
      concentrations of LH and FSH with each of the treatments by comparison with the
      control group. Plasma concentrations of cortisol and fasting blood sugar level as
      well as packed cell volume (PCV) and total plasma protein were recorded to
      monitor the changes of chronic stress in the experimental animals. Changes in
      these parameters were not significant. An intratesticular injection of calcium
      chloride at specified doses could be a suitable method of sterilization in
      preference to surgical castration of goats.

PMID- 15721663
TI  - Estimation of genetic parameters of semen characteristics and reproductive traits
      in AI boars.
AB  - (Co)variance components and further genetic parameters of boar semen
      characteristics and reproductive traits were estimated using the REML procedure
      applied to multi-trait animal models. The calculations were based on data from
      210,733 ejaculates stemming from 2862 AI boars and collected from 1990 to 1997 in
      insemination stations for boars in the Czech Republic. Equal model equations for
      all traits included the AI station and the breed or breed combination as fixed
      effects, the interval between two collections for the boar as covariable and the
      animal and residual effects as random effects. The following heritabilities were
      estimated: semen volume 0.58, sperm concentration 0.49, progressive motion of
      spermatozoa 0.38, abnormal spermatozoa 0.34, number of total spermatozoa 0.42,
      number of insemination doses 0.40, number of piglets born alive 0.08, total
      number of piglets born 0.05 and conception rate 0.29. Heritabilities and genetic
      correlations were estimated on average values for each boar.

PMID- 15721664
TI  - Uterine and fetal asphyxia monitoring in parturient sows treated with oxytocin.
AB  - Oxytocin is used to induce and control parturition, nevertheless, the increase of
      uterine contractions decreases blood flow and gaseous exchange through the womb
      predisposing to intra-partum mortality. The objective of the present study was to
      evaluate the effect of oxytocin on myometrial activity, fetal intrauterine
      hypoxia and postnatal asphyxia in sows during farrowing. Hybrid (n = 120) sows
      approaching the time of farrowing were randomly assigned in two groups of 60
      animals each. Group I (G(1): control) was treated IM with saline solution and
      Group II (G(2)) was injected IM with oxytocin (1IU/6kg LW) as a single dose at
      birth of the first piglet. Both average number of myometrial contractions and
      intensity in G(2) were greater (P < 0.01) as compared with G(1). The mean of
      intra-partum stillbirths (IPS's) and those where fetal cardiac frequency (FCF) or
      heart beats, could not be detected after birth, were greater (P < 0.01) in G(2)
      as compared with G(1). The average decelerations of FCF known as dips II, which
      indicate severe hypoxia, was greater in G(2) (P < 0.01) as compared with that of
      G(1). There was a greater (P < 0.01) number of intra-partum stillbirths, stained
      with severe meconium in G(2) when compared with G(1). Oxytocin treatment
      increased (P < 0.01) the number of pigs born alive with ruptured umbilical cords
      and those with different grades of meconium staining on their skin. It was
      concluded that administration of oxytocin at the onset of parturition increased
      the myometrial activity, decreased fetal cardiac frequency, predisposed the
      rupture of umbilical cords and the degree of meconium staining, and increased
      intra-partum mortality.

PMID- 15721665
TI  - Testosterone immunization blocks the ovulatory process in laying hens without
      affecting ovarian follicular development.
AB  - The role of testosterone in the ovulatory process in hens has been largely
      neglected. The aim of the present study was to evaluate if testosterone plays an
      important role on the ovulatory process in laying hens. The effect of active and
      passive immunization against testosterone on ovarian follicular development and
      oviposition was studied. Egg laying percentage was evaluated in hens actively
      immunized against testosterone-BSA (T-AI; n = 6) or BSA (BSA-AI; n = 6).
      Oviposition was reduced as antibody titer increased in T-AI hens (r = -0.67; P <
      0.01). Ovarian structures were assessed in three animals from each group.
      Follicles reached preovulatory size in both groups, nonetheless, in T-AI hens
      follicles at different stages of regression indicated that ovulation was blocked
      by treatment. In the remaining animals, preovulatory concentrations of
      progesterone and testosterone were determined. A preovulatory surge release of
      progesterone, preceded by a testosterone peak, was observed in the BSA-AI group
      (P < 0.05). In contrast, progesterone in T-AI animals remained at basal
      concentrations. Whereas, testosterone concentrations were significantly greater
      in T-AI as compared with BSA-AI animals (P < 0.05). Finally, to study the effect
      of passive immunization on oviposition, hens were passively immunized (PI) on
      four occasions, on alternate days with anti-T serum (T-PI; n = 10) or anti-BSA
      serum (BSA-PI; n = 8). During the 13-day period that preceded treatment,
      oviposition averaged 94.1%. Forty-eight hours after the first immunization, no
      egg was laid by 8 out of the 10 T-PI hens. During the 10 days following the first
      passive immunization, there was a reduction in the laying percentage that was
      significantly greater in T-PI hens (reduction of 52% in T-PI versus 29% in P-BSA,
      P < 0.01). In summary, these studies show that testosterone immunization hampers
      egg-laying without affecting ovarian follicular development, suggesting that
      testosterone has an important role in the ovulatory process in laying hens.

PMID- 15721666
TI  - Effect of exogenous progesterone and eCG treatment on ovarian follicular dynamics
      in vicunas (Vicugna vicugna).
AB  - The aim of the present study was two-fold. First, to evaluate the effect of
      exogenous progesterone on ovarian follicular dynamics in order to assess its
      ability to synchronize ovarian activity in the vicuna. Secondly, to evaluate the
      ovarian response to the treatment with eCG through the observation of the
      structures developed in the ovaries. Follicular dynamics was monitored daily by
      transrectal ultrasonography in 12 adult, non-pregnant vicunas. Plasma
      progesterone and estradiol-17beta concentrations were measured in blood samples
      collected daily. In experiment 1, intravaginal devices containing 0.33g of
      progesterone were inserted into the vagina and kept in place for 5 days
      (treatment group, n = 8). After progesterone withdrawal, five animals were
      further monitored in order to evaluate the efficacy of the CIDR to synchronize
      the emergence of a dominant follicle. In experiment 2, four females received
      750IU of eCG IM. Two were previously monitored ultrasonographically to confirm
      the absence of a dominant follicle at the beginning of the superstimulatory
      treatment (group A). The other two animals had a CIDR inserted into the vagina
      for 5 days and the superstimulatory treatment was applied 24h after device
      withdrawal (group B). Females from both groups were surgically explored 96 h
      after eCG injection; the ovaries were exposed and the number of newly formed
      structures produced by each ovary was counted. Peak progesterone concentrations
      (25.9 +/- 5.29 nmol l(-1), mean +/- S.E.M.) were attained on day 1 after device
      insertion, remained high until the day of device withdrawal (9.7 +/- 1.98 nmol l(
      1)) and decreased to 5.5 +/- 1.13 nmol l(-1) the day after. There was no follicle
      development to the state of dominance after device insertion. Moreover, mean
      follicle diameter steadily decreased after insertion of the device until the
      minimum mean value (1.85 +/- 0.17 mm) was recorded on day 5 (P = 0.006).
      Similarly, plasma concentrations of estradiol-17beta remained below 35 pmol l(-1)
      during the period of progesterone treatment in all animals and the mean estradiol
      17beta declined with the lowest value (22.1 +/- 2.19 pmol l(-1)) being recorded
      on day 4 after device insertion. After superstimulation of follicular development
      with eCG, the total number of follicles that developed was 33 in group A and 58
      in group B and the mean number of newly developed ovarian structures per female
      was 22.75 +/- 4.26. In conclusion, progesterone released by the CIDR exerts a
      negative effect on ovarian follicular development and function suggesting
      intravaginal devices could be used to synchronize the beginning of follicular
      waves during a superstimulatory treatment. There was also a tendency for greater
      ovarian follicular development when the animals were previously treated with
      progesterone.

PMID- 15721667
TI  - Relationship between total superoxide dismutase activity with lipid peroxidation,
      dynamics and morphological parameters in canine semen.
AB  - There is a lack of information regarding biochemical studies on canine semen. The
      knowledge of canine sperm metabolism is important because this species has
      differences in fertility among males, but biochemical studies are not well
      developed in this species. Reactive oxygen species (ROS) are active molecules
      produced during the oxygen reduction that have been implicated in several
      deleterious effects on the function and viability of spermatozoa when they are
      produced at high concentrations. Peroxidation of the plasma membrane
      phospholipids leads to a loss of motility, viability, and cytosolic elements,
      metabolic changes and structural alterations in spermatozoa. The most important
      antioxidant enzyme involved in ROS detoxification in mammalian spermatozoa is
      superoxide dismutase (SOD). The aims of the present study were to determine the
      presence of SOD-like activity in different fractions of canine semen, and to
      determine the relationship between SOD-like activity and different morphological,
      dynamical and biochemical parameters in canine spermatozoa. We demonstrated the
      presence of SOD-like activity in canine seminal plasma and spermatozoa; the
      negative correlation between SOD-like activity and lipid peroxidation
      concentrations in spermatozoa suggests a protective effect of this enzymatic
      activity against the potential oxidative stress in canine spermatozoa. A
      significant negative correlation between percentage of abnormal spermatozoa, and
      the percentage of progressive motility or vigor was found. Abnormal spermatozoa
      not only showed a deformed shape, moreover there was an energetic motility system
      failure. The presence of SOD-like activity in seminal plasma, spermatic, and
      postspermatic fractions of canine semen was demonstrated for the first time.

PMID- 15721669
TI  - Biomechanical customization: the next generation of laser refractive surgery.

PMID- 15721671
TI  - Neodymium:YAG laser capsulotomy in vitrectomized pseudophakic eyes with
      persistent endotamponade.

PMID- 15721672
TI  - Secondary peripheral iris suture fixation of an acrylic IOL in megalocornea.

PMID- 15721673
TI  - Anterior chamber maintainer: creating an adequate side-port incision in
      complicated circumstances.

PMID- 15721675
TI  - Anterior stromal puncture for recurrent corneal erosion after laser in situ
      keratomileusis.

PMID- 15721677
TI  - Inhibition of lens epithelial cell migration by contact pressure.

PMID- 15721679
TI  - Pseudoaccommodation with forward movement of IOLs.

PMID- 15721680
TI  - Optical coherence tomography of scleral expansion band implantation.

PMID- 15721681
TI  - Subconjunctival lens dislocation.

PMID- 15721682
TI  - Binocular vision impairment after refractive surgery.

PMID- 15721683
TI  - Consultation Section. Refractive surgical problem.

PMID- 15721693
TI  - Corneal power, thickness, and stiffness: results of a prospective randomized
      controlled trial of PRK and LASIK for myopia.
AB  - PURPOSE: To compare the short-, medium-, and long-term changes in corneal optical
      power and corneal aberrations, central corneal thickness, and corneal "stiffness"
      assessed by pneumotonometry readings in patients having laser in situ
      keratomileusis (LASIK) or photorefractive keratectomy (PRK) for myopia. SETTING:
      Department of Ophthalmology, Arhus University Hospital, Arhus, Denmark. METHODS:
      One eye of each of 45 patients with myopia ranging from -6.00 to -8.00 diopters
      (D) (spherical equivalent spectacle refraction [SER]) was randomized to LASIK
      (n=25; mean SER -7.12 D +/- 0.57 [SD]) or PRK (n=20; mean SER -6.91 +/- 0.57 D).
      Data were collected prospectively before and 1, 3, 6, 12, and 36 months after
      surgery. Measurements included corneal topography (TMS-1, Tomey), corneal
      thickness (ultrasound pachymetry), and apparent intraocular pressure (IOP)
      (pneumotonometry). Retreatments were not performed during the first year, and
      retreated eyes were excluded from the 3-year follow-up. Changes in corneal power
      and aberrations, thickness, and apparent IOP were calculated in a pair-wise
      manner for 3 time periods: short term (preoperative to 1 month after surgery),
      medium term (1 to 12 months after surgery), and long term (1 to 3 years after
      surgery). RESULTS: In the short term, corneal power decreased equally in LASIK
      and PRK eyes. Spherical aberrations and coma-like aberrations increased equally,
      while corneal thickness decreased significantly less in LASIK eyes than in PRK
      eyes. The apparent IOP decreased more in LASIK eyes than in PRK eyes. In the
      medium term, corneal power increased significantly in both groups. Spherical
      aberrations decreased significantly in PRK eyes but not in LASIK eyes. From 1 to
      12 months, corneal thickness increased more in PRK eyes than in LASIK eyes.
      During this period, the apparent IOP increased significantly in LASIK eyes. In
      the long term, corneal power and corneal aberrations did not change significantly
      in either group. Corneal thickness increased slightly but significantly in both
      groups. The apparent IOP increased significantly more in PRK eyes. CONCLUSIONS:
      Differences between LASIK and PRK related to time-dependent events affecting
      corneal shape and structural integrity were present. Peripheral changes in flap
      hydration in LASIK eyes and epithelial and/or stromal thickening in PRK eyes
      appeared to be the most important factors in optical power changes in the first
      year after treatment. The changes in apparent IOP suggest that some interlamellar
      healing occurred during the first year after LASIK. After LASIK and PRK, corneal
      bending stiffness seemed permanently decreased, although some restiffening may
      occur in PRK eyes in the long term.

PMID- 15721694
TI  - Differences in nasal and temporal responses of the cornea after photorefractive
      keratectomy.
AB  - PURPOSE: To examine the differences in the biomechanical response of the
      peripheral regions of the cornea after photorefractive keratectomy (PRK).
      SETTING: Department of Ophthalmology, Catholic University of Rome, Rome, Italy.
      METHODS: Preoperative and 1-, 3-, 6-, and 12-month postoperative corneal
      topographies of 70 eyes that had PRK with the Technolas 217C excimer laser
      (Bausch & Lomb) were obtained. The eyes were divided into 4 groups according to
      the preoperative spherical equivalent refraction. Preoperative and follow-up
      topographic data were imported into custom software that computed the average
      composite corneal map and difference maps in each group to scientifically
      evaluate the corneal response to the surgery. The software was also used to
      analyze regional corneal changes after the laser ablation. Corneal peripheries up
      to 9.0 mm were evaluated. RESULTS: The preoperative corneas had a flatter nasal
      periphery than temporal periphery. The corneal surfaces in the right eyes and
      left eyes showed a mirror symmetry. Significant differences in the regional
      response of the cornea were observed (P<.05), with a greater increase in the
      curvature of the nasal periphery than in the temporal periphery. CONCLUSIONS: To
      refine modeling of the cornea, the different regional anatomic features and
      biomechanical responses must be considered. Modifying existing ablation
      algorithms to compensate for the differences between nasal and temporal corneal
      flattening of the preoperative corneal surface and between the nasal and temporal
      responses may improve the postoperative corneal shape and quality of peripheral
      optics.

PMID- 15721695
TI  - Transition zone design and smoothing in custom laser-assisted subepithelial
      keratectomy.
AB  - PURPOSE: To evaluate the results of custom laser-assisted subepithelial
      keratectomy (LASEK) with a specially designed transition zone and smoothing for
      the treatment of refractive errors. SETTING: Department of Ophthalmology,
      Istituto Clinico Humanitas, Rozzano-Milan, Italy. METHODS: This prospective study
      involved myopic eyes having refractive surgery with the butterfly LASEK technique
      and the Nidek EC-5000 excimer laser. The treatment was based on the surgeon's
      analysis of topographic and aberrometric data provided by Final Fit ablation
      software, which features the Custom Aspheric Transition Zone software algorithm.
      After the ablation, smoothing was performed to remove corneal
      microirregularities. RESULTS: Fifty-five eyes of 38 patients were treated. The
      mean preoperative spherical equivalent (SE) refraction was -6.58 diopters (D) +/-
      2.24 (SD) (range -12.13 to -1.75 D). At 1 year, the mean SE refraction was -0.26
      +/- 0.79 D (range -4.00 to +0.75 D). CONCLUSION: The surface ablation technique
      provided satisfactory results and took into account strategies to reduce
      unpredictability factors such as corneal biomechanical forces, haze induced by an
      irregular postoperative surface, and a high curvature gradient in the transition
      zone.

PMID- 15721696
TI  - Topographic and biomechanical differences between hyperopic and myopic laser in
      situ keratomileusis.
AB  - PURPOSE: To evaluate the size, shape, and uniformity of the videokeratographic
      functional optical zone (FOZ) after laser in situ keratomileusis (LASIK) in 2
      cohorts of patients with equivalent amounts of preoperative myopic or hyperopic
      astigmatism. SETTING: Pepose Vision Institute, St. Louis, Missouri, USA. METHODS:
      Eyes with myopic or hyperopic astigmatism (n=27 in each group) that had LASIK
      with the Visx Star S3 laser were retrospectively selected to match for level of
      preoperative refractive error. Slit-scanning videokeratography was performed
      preoperatively and 6 months postoperatively and analyzed using custom software.
      The FOZ was calculated by analyzing refractive power maps using a region-growing
      algorithm. Difference maps were generated from slit images and compared for
      interval change in corneal elevation, tangential curvature, and refractive power.
      The difference maps were also averaged (mean difference maps) for each target
      population. A Zernike decomposition of corneal first-surface elevation was
      performed to compare postoperative values with baseline parameters. RESULTS: The
      mean postoperative refractive sphere at 6 months was -0.17 diopter (D) +/- 0.66
      (SD) and +0.25 +/- 0.85 D in the myopia group and hyperopia group, respectively,
      and the mean postoperative astigmatism, -0.49 +/- 0.32 D and -0.65 +/- 0.52 D,
      respectively (P=.11). Based on the refractive power maps, the mean preoperative
      and postoperative myopic FOZ was 33.09 +/- 7.30 mm(2) and 30.94 +/- 5.43 mm(2),
      respectively, and the mean hyperopic FOZ, 33.19 +/- 7.96 mm(2) and 37.99 +/- 6.88
      mm(2), respectively. After LASIK, there was an increase in magnitude of negative
      anterior corneal surface spherical-like Zernike values in the myopia group
      (P<.0001) and an increase in magnitude of positive spherical-like Zernike values
      in the hyperopia group. Postoperatively, significant induction of corneal surface
      horizontal coma was noted in hyperopic eyes (P<.0001). Hyperopic eyes, on
      average, had larger topographic FOZs after LASIK, but with less uniformity of
      curvature and power change than myopic eyes. CONCLUSIONS: Hyperopic LASIK, which
      involves more transition points along the ablation diameter, produced a less
      uniform topographic FOZ than typical myopic treatments. Less predictable
      biomechanical changes from the circumferential release of tension on collagen
      bundles after midperipheral hyperopic ablation and greater variation in beam
      centration and the angle of incidence may contribute to the greater variability
      in corneal curvature and power in hyperopic LASIK than in myopic LASIK.

PMID- 15721697
TI  - Response of the posterior corneal surface to laser in situ keratomileusis for
      myopia.
AB  - PURPOSE: To describe the response of the posterior corneal surface in laser in
      situ keratomileusis (LASIK) and determine whether residual stromal bed thickness
      or treatment magnitude is predictive of the posterior corneal surface elevation
      after uneventful LASIK. SETTING: A private hospital-based refractive surgery
      practice, Hong Kong SAR, China. METHODS: Orbscan I (Bausch & Lomb)
      videokeratography examinations were performed on 1124 patients before and 6
      months after LASIK for myopia (mean -6.81 diopters [D] +/- 2.52 [SD]; range -0.88
      to -14.50 D). The best-fit sphere (BFS) over the central 9.0 mm region of the
      posterior corneal surface before and after treatment was compared. The location
      and magnitude of the 1.0 mm diameter region of highest elevation above the BFS
      for the central 4.0 mm diameter zone were calculated before and after treatment
      and compared using a paired t test. Stepwise regression was used to model the
      best predictors of the posterior radius of the BFS and the central elevation of
      the corneal surface above the BFS before and after treatment. RESULTS: The mean
      radius of curvature of the posterior surface BFS decreased 0.10 mm after LASIK,
      from 6.31 to 6.21 mm (P<.001). Elevation above this BFS was increased 10 microm
      within a 1.00 mm diameter region of interest, and this was correlated with
      postoperative corneal thickness, inferotemporal decentration of the highest
      point, residual myopia, and steeper central posterior radius of curvature.
      CONCLUSIONS: No eye was diagnosed with corneal ectasia at the time of the 6-month
      postoperative visit. After LASIK, there was a decreased radius of curvature for
      the BFS of the posterior corneal surface, with the highest elevation point
      located paracentrally. These findings are similar to the anterior corneal surface
      changes observed in corneal ectasia after LASIK but smaller in magnitude.

PMID- 15721698
TI  - Model for nonectatic increase in posterior corneal elevation after ablative
      procedures.
AB  - PURPOSE: To evaluate the response of the posterior cornea after uneventful laser
      in situ keratomileusis (LASIK) with scanning-slit videokeratography using the
      change in elevation as a measure of biomechanical remodeling. SETTING: Hong Kong
      Sanatorium and Hospital, Hong Kong, China. METHODS: Three schematic models of
      possible posterior corneal response mechanisms to laser refractive surgery were
      proposed: model A, isolated central bulging; model B, forward shift over a large
      region of the posterior surface; model C, backward peripheral movement into the
      anterior chamber. A retrospective study was performed to determine which model
      was consistent with posterior corneal behavior in 2380 eyes of 1255 patients
      after myopic LASIK performed with the Technolas 217 laser (Bausch & Lomb).
      Patients received preoperative and 6-month postoperative Orbscan I (version 2.0,
      Bausch & Lomb) examinations. Preoperative posterior elevation maps were
      subtracted from postoperative maps of 2380 eyes using 3 fitting protocols.
      Difference maps were averaged and the results compared to the proposed schematic
      models. All topography data processing was done using the Ohio State University
      Corneal Topography Tool. RESULTS: Significant central increases in posterior
      elevation corresponded with significant peripheral decreases in posterior
      elevation. This pattern is consistent with schematic model C, backward peripheral
      movement of the posterior cornea, possibly due to a differential pattern of
      swelling. CONCLUSIONS: Increases in central posterior corneal elevation after
      LASIK appear to be dominated by backward peripheral corneal swelling into the
      anterior chamber rather than forward "bulging" of the central posterior cornea.
      This is consistent with stable remodeling of the corneal shape due to a
      surgically induced change in structure and fluid balance, rather than an ectatic
      event.

PMID- 15721699
TI  - Long-term follow-up of ultrathin corneas after surface retreatment with
      phototherapeutic keratectomy.
AB  - PURPOSE: To evaluate visual acuity and long-term stability after phototherapeutic
      keratectomy (PTK) in patients with corneal thickness less than 400 microm and
      cornea-related vision problems. SETTING: Department of Ophthalmology, Istituto
      Clinico Humanitas, Rozzano-Milan, Italy. METHODS: This retrospective study
      comprised 48 eyes that had PTK for complications after photorefractive
      keratectomy that removed more than 200 microm of tissue. Phototherapeutic
      keratectomy was performed with the Nidek EC-5000 excimer laser with 10 Hz
      frequency, intraoperative topography, and masking fluid over an ablation diameter
      of 10.0 mm. The follow-up was 5 years. The mean preoperative best spectacle
      corrected visual acuity (BSCVA) was 0.2 +/- 0.09 (SD) with -2.53 +/- 2.34
      diopters (D), and the mean pachymetry was 390 +/- 38 microm. The efficacy
      parameters were pachymetry and visual acuity at 1 year and the stability
      parameters, optical refraction, corneal curvature (calculated as the mean
      curvature over the entire 3.0 mm and 5.0 mm central zones), and pachymetry from 1
      to 5 years. RESULTS: At 1 year, the mean BSCVA was 0.6 +/- 0.72 with -2.15 +/-
      1.67 D and the mean pachymetry, 341 +/- 40 microm. At 5 years, the mean BSCVA was
      0.7 +/- 0.15 with -2.33 +/- 1.12 D and the mean pachymetry, 339 +/- 48 microm. In
      all patients, there was an improvement of 4 or more Snellen lines. Statistical
      evaluation of refraction and corneal curvature values at 1 and 5 years indicated
      no statistically significant differences. CONCLUSIONS: After PTK in eyes with
      ultrathin corneas, there was significant improvement in BSCVA and long-term
      stability of the optical refraction, corneal curvature, and pachymetry. In
      selected cases, 10.0 mm ablation zone PTK may be an alternative to penetrating
      keratoplasty, offering long-term corneal stability.

PMID- 15721700
TI  - Cornea-sparing laser in situ keratomileusis: ablation on the flap.
AB  - PURPOSE: To evaluate the safety and efficacy of laser ablation on the flap as a
      treatment for a refractive error. SETTING: Laser Sight Centres, Sydney,
      Australia. METHODS: In this noncomparative case series, 142 treatments were
      performed in 98 patients using cornea-sparing laser in situ keratomileusis
      (LASIK) with ablation of the corneal flap and, in some cases, also the stromal
      bed for spherical equivalent (SE) refractive errors from -0.50 diopter (D) to 
      12.38 D. The procedure was performed as a primary treatment in 104 eyes, an
      initial enhancement in 32 eyes, and a second enhancement in 6 eyes. Data were
      extracted for analysis by retrospective review of patients' charts. RESULTS:
      After LASIK, the mean SE was -0.20 D +/- 0.47 (SD) (range +0.87 to -2.35 D)
      excluding eyes with monovision. The 6 eyes with monovision had a mean SE of -1.90
      D with myopia of -1.70 D (range -1.00 to -3.00 D) and mean astigmatism of -0.37 D
      (range 0 to -0.75 D). Excluding eyes with monovision, 97% of eyes achieved an
      uncorrected visual acuity of 6/12 or better and 64% of eyes, better than or equal
      to 6/6. Ninety-six percent were within +/-1.0 D of the intended correction (SE).
      The safety index was 1.02 and the efficacy index, 0.8. CONCLUSIONS: Laser
      ablation of the corneal flap achieved good visual results and enabled
      preservation of the posterior corneal stroma. This technique may aid the
      prevention of corneal keratectasia following LASIK.

PMID- 15721701
TI  - Randomized prospective clinical study comparing induced aberrations with
      IntraLase and Hansatome flap creation in fellow eyes: potential impact on
      wavefront-guided laser in situ keratomileusis.
AB  - PURPOSE: To measure and compare the changes in objective wavefront aberration and
      subjective manifest refraction after laser in situ keratomileusis (LASIK) flap
      creation with a mechanical microkeratome and a femtosecond laser. SETTING:
      Private practice refractive surgery center, Irvine, California, USA. METHODS:
      This randomized prospective study comprised 9 patients (18 eyes) treated with a 2
      step LASIK procedure: lamellar keratectomy with a Hansatome microkeratome (Bausch
      & Lomb) or the IntraLase femtosecond laser in fellow eyes followed by non
      wavefront-guided (standard) excimer laser treatment with the Technolas 217A
      (Bausch & Lomb) excimer laser 10 weeks later. Fellow eyes were matched to within
      0.75 diopter (D) sphere and 0.50 D cylinder. Patients were followed for 3 months
      after excimer laser treatment. Preoperative and post-flap creation wavefront
      aberrometry using a Hartmann-Shack aberrometer and manifest refraction were
      compared between the 2 groups. The same tests were performed 3 months after
      excimer laser ablation. RESULTS: Statistically significant changes were seen in
      defocus wavefront aberrations after Hansatome (P=.004) and IntraLase (P=.008)
      flap creation. A hyperopic shift in manifest refraction was noted in the
      Hansatome group after the creation of the corneal flap (P=.04); no statistically
      significant changes in manifest refraction were seen in the IntraLase group.
      Statistically significant changes in total higher-order aberrations (HOAs)
      (trefoil and quadrafoil Zernike terms) were seen after flap creation in the
      Hansatome group (P=.02). No significant changes in HOAs were noted after flap
      creation in the IntraLase group. After the flap was relifted and standard excimer
      laser ablation was performed, a statistically significant increase in coma
      occurred in the Hansatome group (P=.008). Standard refractive outcomes in the 2
      groups were similar. CONCLUSIONS: The creation of the LASIK flap alone can modify
      the eye's optical characteristics in low-order aberrations and HOAs. A
      significant increase in HOAs was seen in the Hansatome group but not in the
      IntraLase group. This may have significant clinical implications in wavefront
      guided LASIK treatments, which are based on measurements made before flap
      creation.

PMID- 15721702
TI  - Prediction of flap response.
AB  - PURPOSE: To find predictors of the induced biomechanical and optical effects of
      lamellar flap creation on the cornea. SETTING: Optimed Eye and Laser Clinic,
      Pretoria, South Africa, and the Department of Ophthalmology and Biomedical
      Engineering Center, The Ohio State University, Columbus, Ohio, and Bausch & Lomb
      Vision Research Laboratory, Rochester, New York, USA. METHODS: This prospective
      study monitored the refractive, wavefront aberration, and corneal topographic
      changes in 29 eyes of 15 patients for 3 months after the creation of a corneal
      lamellar flap. The main outcome measures for statistical analysis were
      refraction, total corneal thickness, residual corneal bed thickness, horizontal
      white-to-white corneal diameter, horizontal flap diameter, topography data, and
      wavefront data. RESULTS: Statistically significant changes were seen in the
      autorefraction mode. Wavefront data showed significant change in 4 Zernike modes
      90/180-degree astigmatism, vertical coma, horizontal coma, and spherical
      aberration. The topography data indicated the corneal biomechanical response was
      significantly predicted by stromal bed thickness in the early follow-up period
      and by total corneal pachymetry and flap diameter in a 2-parameter statistical
      model in the late follow-up period. CONCLUSIONS: Uncomplicated lamellar flap
      creation is responsible for systematic changes in corneal topography and
      induction of higher-order optical aberrations. Predictors of this response
      include stromal bed thickness, flap diameter, and total corneal pachymetry.

PMID- 15721703
TI  - Corneal flap thickness and topography changes induced by flap creation during
      laser in situ keratomileusis.
AB  - PURPOSE: To determine the corneal flap thickness profile produced by 3
      microkeratomes and the topographic changes induced by flap creation in laser in
      situ keratomileusis (LASIK). SETTING: Cornea and Refractive Surgery Unit,
      Instituto de Microcirugia Ocular de Barcelona, Autonoma University, Barcelona,
      Spain. METHODS: In this prospective consecutive nonrandomized comparative study,
      patients were divided into 2 groups. In Group 1 (75 eyes), 3 microkeratomes were
      used: Moria LSX One, Moria M2, and Amadeus (AMO); 25 eyes per microkeratome.
      Pachymetry was measured with a DGH pachymeter in the center of the cornea and 3.0
      mm from the center at 4 cardinal points (superior, inferior, nasal, and temporal;
      3 measurements at each point) before and after the cut. The flap thickness in
      each sector was calculated by subtracting the mean post-flap corneal thickness
      from the mean pre-flap corneal thickness. In Group 2 (33 eyes), the M2
      microkeratome with a 130 microm plate was used to create a superotemporal hinged
      flap (9 eyes) or a superonasal hinged flap (24 eyes). The topographic change
      induced by the microkeratome cut was evaluated using 4 sequential data
      acquisitions by the Keratron Scout topographic unit (Optikon) before and
      immediately after the cut (before laser ablation). Cardinal and oblique
      astigmatism and change in the axis were calculated by vectorial analysis of the
      simulated keratometry. Topographic Zernike analysis was performed in a subgroup.
      RESULTS: With the LSX One microkeratome, the mean flap thickness was 151.7 microm
      centrally, 161.9 microm superiorly, 151.4 microm inferiorly, 156.1 microm
      temporally, and 167.5 microm nasally. There was no statistically significant
      difference between the areas studied (P<.05). With the M2, the mean flap
      thickness was 131.7 microm centrally, 155.5 microm superiorly, 146.7 microm
      inferiorly, 143.7 microm temporally, and 160.5 microm nasally. There was a
      statistically significant difference between flap thickness centrally and in the
      other areas (P>.05). With the Amadeus microkeratome, the mean flap thickness was
      140.0 microm centrally, 152.5 superiorly, 128.5 microm inferiorly, 145.0 microm
      temporally, and 147.0 microm nasally. Statistically significant differences
      (P>.05) were found in the 4 sectors of the flap. With vectorial analysis, there
      was no statistically significant difference between superonasal and
      superotemporal hinge placement in the cardinal and oblique components but there
      was a statistically significant difference in the axis change with both
      placements (P>.05). CONCLUSIONS: The LSX One microkeratome was the most
      predictable. A significant difference was noted in all sectors except superiorly
      with the M2 and in all sectors with the Amadeus. No differences between nasal and
      superior hinge placement were found with the M2. Topographic Zernike analysis
      demonstrated a difference in the orientation of the induced coma as a function of
      hinge position.

PMID- 15721704
TI  - Femtosecond laser versus mechanical keratome flaps in wavefront-guided laser in
      situ keratomileusis: prospective contralateral eye study.
AB  - PURPOSE: To compare the outcomes of wavefront-guided laser in situ keratomileusis
      (LASIK) performed using the IntraLase femtosecond laser with the outcomes using
      the Hansatome mechanical microkeratome. SETTING: Private clinic, Overland Park,
      Kansas, USA. METHODS: In a prospective contralateral-eye study performed under
      institutional review board supervision, 51 consecutive patients (102 eyes) had
      bilateral wavefront-guided LASIK for myopia using the Alcon LADARVision laser.
      One eye of each patient was randomized to have the flap created with the
      IntraLase femtosecond laser and the other flap using a standard compression head
      Hansatome microkeratome. All other treatment parameters were the same. RESULTS:
      The IntraLase group had significantly better mean uncorrected visual acuity
      (UCVA) at all intervals from 1 day to 3 months postoperatively. The mean
      spheroequivalent at 3 months was more myopic with the Hansatome (-0.34 diopter
      [D] +/- 0.28 [SD]) than with the IntraLase (-0.19 +/- 0.24 D) (P<.01). The mean
      residual astigmatism at 3 months was also significantly higher in the Hansatome
      group than in the IntraLase group (0.32 +/- 0.25 D and 0.17 +/- 0.20 D,
      respectively) (P<.01). The differences in UCVA persisted after spheroequivalent
      outcomes were controlled for but equilibrated when the analysis was modified to
      control for manifest postoperative astigmatism. Aberrometry showed significantly
      higher astigmatism and trefoil in the Hansatome group. Recovery of corneal
      sensation and epithelial integrity was similar between groups. CONCLUSIONS: The
      statistically better UCVA and manifest refractive outcomes after LASIK with the
      IntraLase femtosecond laser may be the result of differences in postoperative
      astigmatism and trefoil. These findings are consistent with previous findings of
      better astigmatic outcomes with the IntraLase laser and may have clinical
      significance for wavefront-guided treatments.

PMID- 15721705
TI  - Causes of spherical aberration induced by laser refractive surgery.
AB  - PURPOSE: To develop a corneal model to better explain how refractive surgery
      procedures induce spherical aberration. SETTING: Department of Ophthalmology and
      Center for Visual Science, University of Rochester, Rochester, New York, USA.
      METHODS: The preoperative cornea was modeled as a rotationally symmetric surface
      with various radii of curvature and asphericities. The postoperative cornea was
      defined as the difference between the preoperative cornea and an ablation
      thickness profile computed based on the Munnerlyn equation. A ray-tracing program
      and Zernike polynomial fitting were used to calculate the induced amount of
      spherical aberration assuming a fixed ablation depth per pulse or a variable
      ablation depth depending on the incidence angle of each pulse on the cornea. A
      biological eye model of the corneal surface change after laser refractive surgery
      was also developed to explain the induced spherical aberrations after myopic and
      hyperopic treatments. RESULTS: The clinical data showed that positive spherical
      aberration was induced after myopic correction and negative spherical aberration
      increased after hyperopic correction. In contrast, assuming a fixed ablation
      depth per pulse, the theoretical prediction was that negative spherical
      aberration with myopic treatment and positive spherical aberration with hyperopic
      treatment would increase. However, when assuming a variable ablation depth per
      pulse caused by non-normal incidence of laser spot on the cornea, the
      theoretically predicted induction of spherical aberration tends to fit better
      with the myopic and hyperopic clinical data. The effect of a variable ablation
      depth accounted for approximately half the clinically observed amount of
      spherical aberration. The biological model of the corneal surface change used to
      explain this remaining discrepancy showed the magnitude of the biological
      response in myopic correction is 3 times smaller than in hyperopic correction and
      that the direction of the biological response in hyperopic treatment is opposite
      that in myopic treatment. CONCLUSIONS: This nontoric eye model, which separates
      the effects of differences in ablation efficiency and biological corneal surface
      change quantitatively, explains how spherical aberration is induced after myopic
      and hyperopic laser refractive surgery. With the corneal topographic data, this
      model can be incorporated into the ablation algorithm to decrease induced
      spherical aberrations, improving the outcomes of conventional and customized
      treatments.

PMID- 15721706
TI  - Computational modeling of mechanical anisotropy in the cornea and sclera.
AB  - PURPOSE: To determine the biomechanical deformation of the cornea resulting from
      tissue cutting and removal by use of a new computational model and to investigate
      the effect of mechanical anisotrophy resulting from the fibrillar architecture.
      SETTING: Department of Mechanical Engineering, Stanford University, Stanford,
      California, USA. METHODS: A mathematical model for a typical lamella that
      explicitly accounts for the strain energy of the collagen fibrils, extrafibrillar
      matrix, and proteoglycan cross-linking was developed. A stromal model was then
      obtained by generalized averaging of the lamella properties through the stromal
      thickness, taking into account the preferred orientations of the collagen
      fibrils, which were obtained from x-ray scattering data. RESULTS: The model was
      used to predict astigmatism induced by a tunnel incision in the sclera, such as
      is used for cataract extraction and intraocular lens implantation. The amount of
      induced cylinder was in good agreement with published clinical data. Results show
      it is important for the model to incorporate preexisting corneal physiological
      stress caused by intraocular pressure. CONCLUSIONS: The mathematical model
      described appears to provide a framework for further development, capturing the
      essential features of mechanical anisotropy of the cornea. The tunnel incision
      simulation indicated the importance of the anisotropy in this case.

PMID- 15721707
TI  - Influence of corneal biomechanical properties on intraocular pressure
      measurement: quantitative analysis.
AB  - PURPOSE: To understand and quantify intraocular pressure (IOP) measurement errors
      introduced by corneal variables during applanation tonometry using a cornea
      biomechanical model. SETTING: Department of Ophthalmology, Biomedical Engineering
      Center, The Ohio State University, Columbus, Ohio, USA. METHODS: The model
      assumed an overall resultant pressure that was based on the summation of the
      applanation pressure, the true IOP, and the surface tension caused by the tear
      film to determine the final deformation of the corneal apex during IOP
      measurement. Corneal resistance was varied according to the cornea's
      biomechanical properties, thickness, and curvature, and the effect of each
      variable on the accuracy of IOP tonometry readings was examined quantitatively.
      RESULTS: The model demonstrated that tonometry readings do not always reflect
      true IOP values. They deviate when corneal thickness, curvature, or biomechanical
      properties vary from normal values. Based on the model, predicted IOP readings
      have a 2.87 mm Hg range resulting from the variation in the corneal thickness in
      the normal population and a 1.76 mm Hg range from the variation in the corneal
      radius of curvature. Considering that Young's modulus of the corneal varies from
      0.1 to 0.9 MPa in the normal population, the model predicts tonometry IOP
      readings will have a range of 17.26 mm Hg because of the variation in this
      corneal biomechanical parameter alone. CONCLUSIONS: The simulation based on the
      model demonstrated quantitatively that variations in each corneal variable cause
      errors in tonometry IOP readings. The simulation results indicate that
      differences in corneal biomechanics across individuals may have greater impact on
      IOP measurement errors than corneal thickness or curvature.

PMID- 15721708
TI  - Determining in vivo biomechanical properties of the cornea with an ocular
      response analyzer.
AB  - PURPOSE: To study the results of an ocular response analyzer (ORA) to determine
      the biomechanical properties of the cornea and their relationship to intraocular
      pressure (IOP). SETTING: Reichert Inc., Depew, New York, USA. METHODS: The ORA
      (Reichert) makes 2 essentially instantaneous applanation measurements that permit
      determination of corneal and IOP effects. RESULTS: Measurements of several
      populations indicate that corneal hysteresis, a biomechanical measure, varied
      over a dynamic range of 1.8 to 14.6 mm Hg and was only weakly correlated with
      corneal thickness (r(2)=0.12); this is related to the observation that some
      subjects with relatively thick corneas have less-than-average corneal hysteresis.
      Corneal hysteresis changes diurnally, presumably as a result of hydration
      changes. Keratoconus, Fuchs' dystrophy, and post-LASIK patients demonstrated low
      corneal hysteresis. CONCLUSION: The corneal hysteresis biomechanical measure may
      prove valuable for qualification and predictions of outcomes of refractive
      surgery and in other cases in which corneal biomechanics are important.

PMID- 15721709
TI  - Dynamic corneal imaging.
AB  - PURPOSE: To determine the clinical practicability of in vivo dynamic corneal
      imaging (DCI) to assess the individual elastic properties of normal human eyes,
      eyes with abnormal findings, and eyes after refractive surgery. SETTING:
      University Eye Clinic, Paracelsus Private Medical University, Salzburg, Austria.
      METHODS: The DCI method uses sagittal, stepwise, central indentation of the
      cornea with electronically controlled microprecision motors and sequential
      registration of videotopography images. The indentation steps are preselected and
      range from 50 to 800 mum. The computerized analysis of the videotopography images
      captured during the process uses Zernike polynomials to establish a newly defined
      flexing curve for normal eyes and eyes with abnormal findings. RESULTS: Dynamic
      corneal imaging was done in 187 eyes of 103 patients who had clinically healthy
      corneas, distinct keratoconus, or previous refractive surgery. The method rapidly
      evaluated artificially and reversibly induced changes in corneal topography in a
      clinical setting using a modified Placido disk-based computer-assisted
      videokeratography system with a small cone. In early analysis, the flexing curve
      showed a significant correlation with the applied indentation depth. Factors
      influencing the shape of the curve were central corneal thickness, intraocular
      pressure, and patient age. The DCI method also allowed easy examination of
      keratoconic corneas and corneas after refractive surgery. CONCLUSIONS: Dynamic
      corneal imaging induced a reproducible and reversible change in corneal
      topography corresponding to the different indentation depths. The results
      indicate that several clinical parameters are correlated with corneal elastic
      behavior in vivo and that the technology could increase the predictability of
      refractive corneal surgery and help in the early diagnosis of corneal diseases
      and with newly developed therapies.

PMID- 15721710
TI  - Interferometric technique to measure biomechanical changes in the cornea induced
      by refractive surgery.
AB  - PURPOSE: To develop a technique to quantify biomechanical changes in the cornea
      after microkeratome incisions as would be performed in laser in situ
      keratomileusis. SETTING: St Thomas' Hospital, London, and the Wolfson School of
      Mechanical and Manufacturing Engineering, Loughborough University, Loughborough,
      United Kingdom. METHODS: Corneal displacements of whole sheep eyes were studied
      under hydrostatic loading using electronic speckle pattern interferometry before
      and after microkeratome incisions. RESULTS: After hydrostatic loading, there was
      a 20.7% increase in corneal displacement in corneas with microkeratome incisions
      compared to unoperated corneas; this was statistically significant (P=.0068,
      unpaired t test). CONCLUSIONS: Results show that in the formation of the
      microkeratome flap, collagen fibers are severed and minimal biomechanical loading
      is distributed through the flap. Corneal biomechanical integrity is compromised
      after microkeratome incisions.

PMID- 15721711
TI  - Corneal first-surface aberration analysis of the biomechanical effects of
      astigmatic keratotomy and a microkeratome cut after penetrating keratoplasty.
AB  - Astigmatic keratotomy (AK) was performed in a patient after penetrating
      keratoplasty (PKP) for keratoconus to reduce high post-PKP astigmatism. The
      procedure led to a significant decrease in astigmatism, but corneal higher-order
      aberrations (HOAs) increased. After PKP, the patient was scheduled for 2-step
      laser in situ keratomileusis (LASIK) to correct myopia and astigmatism. One day
      after the microkeratome cut, a decrease of -2.75 diopters in the spherical
      equivalent (SE) was noted. Although subjective manifest cylinder and corneal
      spherical aberrations were marginally affected, a marked decrease in coma and
      other HOAs could be observed. One month after the cut, the SE was unchanged.
      Excimer laser ablation was not performed as the patient was satisfied with the
      result and refused further treatment. This case shows that AK cuts can induce
      HOAs and a single microkeratome cut performed in corneal grafts can have strong
      biomechanical effects on lower-order aberrations and HOAs. If LASIK is planned
      after PKP, a 2-step approach is recommended to anticipate biomechanical effects
      and avoid overcorrection or undercorrection.

PMID- 15721712
TI  - Corneal modeling of keratoconus by conductive keratoplasty.
AB  - We evaluated the effect of conductive keratoplasty (CK) applications for corneal
      modeling to treat keratoconus or post-laser in situ keratomileusis (LASIK)
      corneal ectasia in 3 patients. Treating keratoconus with CK applications resulted
      in more regular topography with visual improvement.

PMID- 15721713
TI  - Post-LASIK myopic shift after a trek in the North Pole.
AB  - Bilateral laser in situ keratomileusis was performed in a 37-year-old male ethnic
      Chinese adventurer. Eight weeks postoperatively, the patient made an unassisted
      trek to the geographic North Pole. After 2 weeks in this environment, a myopic
      shift of more than -1.50 diopters occurred in both eyes. The myopic shift
      resolved over 2 months when the patient returned to a tropical climate. Using
      Orbscan corneal topography, we propose that the myopic shift was attributed to
      biomechanical changes in the cornea induced by corneal dehydration in the Arctic
      environment.

PMID- 15721714
TI  - Transient keratectasia caused by intraocular pressure elevation after laser in
      situ keratomileusis.
AB  - Transient keratectasia developed in association with a marked intraocular
      pressure (IOP) elevation in a 26-year-old man who had laser in situ
      keratomileusis (LASIK) for myopia of -9.0 diopters. The keratectasia subsided
      promptly after the IOP was normalized by an intravenous administration of
      mannitol. Keratectasia did not recur. Intraocular pressure elevation can cause
      keratectasia in a structurally compromised cornea after LASIK.

PMID- 15721715
TI  - Orbscan computerized topography: attributes, applications, and limitations.
AB  - An extensive electronic search was undertaken in January 2004 to identify all
      relevant peer-reviewed publications on Orbscan slit-scanning/Placido computerized
      topography. Ninety-one publications were identified. These address elevation
      topography and best-fit sphere, accuracy and repeatability of anterior and
      posterior corneal elevation and keratometric maps, comparison of Orbscan-acquired
      data and Placido-based computerized videokeratography instruments, pachymetry
      measurement and correlation with ultrasound, screening eye-bank corneas,
      detection of keratoconus, identifying corneal ectasia after refractive surgery,
      and miscellaneous applications. Studies were analyzed and critically compared in
      relation to attributes, applications, and limitations of Orbscan corneal
      topography. The review highlights advantages of this technique in assessing the
      cornea in health and disease and after surgery and identifies specific aspects
      that require further investigation and clarification.

PMID- 15721717
TI  - Inadvertent descemetorhexis.

PMID- 15721716
TI  - Refractive Surgery Survey 2004.
AB  - To determine the refractive surgery (RS) preferences of ophthalmologists
      worldwide, questionnaires were sent to 8897 members of the American Society of
      Cataract and Refractive Surgery. A total of 1053 questionnaires were returned by
      the deadline. The practice distribution included 29.5% cataract surgeons, 48.8%
      comprehensive ophthalmologists, 11.6% RS specialists, 5.1% cornea and external
      disease specialists, 1.9% glaucoma specialists, 1.1% retina specialists, and
      <1.0% oculoplastics/pediatrics/researchers/retired. Results were compared with
      those in the 2003 survey and demonstrate that refractive surgery continues to
      develop and change.

PMID- 15721718
TI  - Use of trypan blue to confirm the patency of filtering surgery.

PMID- 15721719
TI  - An explanation for patient intraocular instrument visualization.

PMID- 15721720
TI  - Trabeculotome-guided unroofing of Schlemm's canal.

PMID- 15721721
TI  - Renal effects of intraoperative atrial natriuretic peptide.

PMID- 15721722
TI  - Effects of atrial natriuretic peptide at a low dose on water and electrolyte
      metabolism during general anesthesia.
AB  - STUDY OBJECTIVE: To assess the hemodynamic, renal, and endocrine effects of small
      continuous doses of atrial natriuretic peptide (ANP) in patients anesthetized
      with sevoflurane for gastrectomy. DESIGN: Prospective randomized study. SETTING:
      Operating room and wards of a university hospital. PATIENTS: 20 ASA physical
      status I and II patients scheduled for gastrectomy. INTERVENTION: Atrial
      natriuretic peptide (0.05 microg/kg/min; ANP group, n = 10) or saline (control
      group, n = 10) was infused continuously for 2 hours beginning at the start of the
      operation. MEASUREMENTS: Plasma concentrations of ANP, brain natriuretic peptide,
      cortisol, angiotensin II, and aldosterone; plasma renin activity; serum and
      urinary sodium, potassium, and chloride; and urinar output. MAIN RESULTS: The ANP
      group showed much greater urine volume and sodium, potassium, and chloride
      excretion than the control group, although the ANP group had a lower arterial
      blood pressure. The infusion did not affect surgery-induced increases in
      hormones. No patients experienced excessive hypotension, bradycardia, or other
      perioperative complications. CONCLUSIONS: Continuous intravenous infusion of ANP
      at 0.05 microg/kg/min during gastrectomy was associated with greater water and
      electrolyte excretion unaccompanied by changes in potentially interacting
      hormones. Low-dose infusion may be particularly safe and useful for controlling
      water and electrolyte metabolism intraoperatively.

PMID- 15721723
TI  - Effect of inspiratory time on tidal volume delivery in anesthesia and intensive
      care unit ventilators operating in pressure control mode.
AB  - STUDY OBJECTIVE: To compare the effect of inspiratory time and lung compliance on
      tidal volume (Vt) delivery in anesthesia and intensive care unit (ICU)
      ventilators operating in pressure control mode. SETTING: Respiratory research
      laboratory of a tertiary care medical center. DESIGN: Two anesthesia ventilators
      with pressure control capability (Narkomed 6000, Drager Medical, Inc, Telford,
      Pa, and the Datex-Ohmeda Aestiva 5, Datex-Ohmeda, Inc, Madison, Wis) and one
      critical care ventilator (Puritan Bennett 7200, Puritan-Bennett, Pleasanton,
      Calif) were studied under varying inspiratory time and lung compliance conditions
      using a mechanical lung model. INTERVENTION: Each ventilator was set to pressure
      control mode at a fixed inspiratory/expiratory (I/E) ratio. The respiratory rate
      (RR) was varied between 6 and 28 breaths per minute. Lung compliance and
      inspiratory time settings were set to simulate clinical conditions known to
      affect anesthesia ventilator performance. MEASUREMENTS: Inspiratory flow, Vts,
      and peak airway pressures were measured using the on-board monitor for each
      ventilator, and confirmed with the Bicore CP-100 pulmonary mechanics monitor
      (Bicore Monitoring Systems, Inc, Irvine, Calif). To assess differences in
      inspiratory flow between ventilators, airway pressures were continuously
      monitored during inspiration. MAIN RESULTS: Increasing RRs caused delivered Vts
      to decrease for all ventilators. However, decreases in Vts were significantly
      larger for anesthesia than for ICU ventilators. At a lung compliance of 0.02 L/cm
      H(2)O and set Vt of 700 mL, Vt delivery for the Puritan Bennett 7200 ventilator
      remained at 88% of baseline, but decreased to 76% for the Aestiva 5 when RRs were
      increased from 6 to 28 breaths per minute (P < .0025). Airway pressure tracings
      demonstrated a slower increase in inspiratory airway pressure for the Aestiva 5
      than for the other ventilators. CONCLUSION: Differences in inspiratory flow
      delivery between ICU and anesthesia ventilators can cause differences in Vt
      delivery when the pressure control mode is used at high RRs. These differences
      can significantly impact the perioperative care of critically ill patients
      requiring ventilatory support.

PMID- 15721724
TI  - Recovery and cognitive function after fentanyl or remifentanil administration for
      carotid endarterectomy.
AB  - STUDY OBJECTIVE: To compare recovery and restoration of cognitive function after
      fentanyl-propofol or remifentanil-propofol anesthesia administration in patients
      undergoing carotid endarterectomy. DESIGN: Randomized, double-blind, prospective
      study. SETTING: Department of Anesthesiology, University hospital. PATIENTS:
      Seventy patients with ASA physical statuses II and III (53 men and 17 women)
      undergoing elective carotid endarterectomy. INTERVENTIONS: Anesthetic technique
      and drugs were identical in the 2 groups, with the exception of remifentanil and
      fentanyl administration. Induction of anesthesia was obtained with a bolus dose
      of propofol (1-2 mg/kg), maintenance was achieved with a propofol infusion
      according to hemodynamics and nitrous oxide/oxygen (FIO(2), 0.50). Muscle
      relaxation was achieved with rocuronium. The remifentanil group received 1
      microg/kg of remifentanil as a single dose during the induction of anesthesia and
      0.5 microg/kg per minute as an infusion throughout the procedure. The fentanyl
      group received 2 microg/kg of fentanyl as a single dose during the induction of
      anesthesia. MEASUREMENTS: Intraoperative hemodynamic adverse events were
      recorded. All patients were also evaluated with regard to their recovery and the
      restoration of their cognitive function, recording the immediate recovery times
      and using the Aldrete score 15 and 60 minutes after surgery and the Hasegawa
      scale 6 hours after surgery. For evaluation of postoperative pain, the Numeric
      Pain Scale (0-10) was used. MAIN RESULTS: Patients receiving remifentanil had
      significantly (P < .05) fewer episodes of intraoperative hypertension and needed
      nitroglycerine administration less frequently (P < .05) than those receiving
      fentanyl. Immediate recovery was significantly earlier (P < .05) with
      remifentanil (eye opening, 5.1 +/- 1.3 [remifentanil] and 7.2 +/- 3.7 [fentanyl]
      minutes; extubation time, 5.4 +/- 1.9 [remifentanil] and 7.8 +/- 4.1 [fentanyl]
      minutes). The Hasegawa Dementia Scale scores 6 hours after surgery and Aldrete
      scores 15 and 60 minutes after surgery did not differ significantly between the 2
      groups. Pain levels were also similar for patients taking remifentanil and
      fentanyl. CONCLUSIONS: Although intraoperative hemodynamics were better preserved
      and immediate recovery was more rapid with remifentanil, overall postoperative
      recovery and restoration of cognitive functions as well as postoperative pain
      intensity seem to be similar for patients receiving remifentanil and for those
      receiving fentanyl combined with propofol for carotid endarterectomy operations.

PMID- 15721725
TI  - Postoperative outcome of patients with narcolepsy. A retrospective analysis.
AB  - STUDY OBJECTIVE: To determine the postoperative outcome of narcolepsy patients, a
      population that may be at increased risk of perioperative complications,
      including postoperative hypersomnia, prolonged emergence after general
      anesthesia, and apnea. DESIGN: Retrospective chart review. SETTING: Academic
      medical center. MEASUREMENTS: The perioperative outcome of pharmacologically
      treated narcolepsy patients, diagnosed at the Mayo Clinic sleep laboratory
      between January 1, 1965, and December 31, 2001, was studied. A total of 37
      narcolepsy patients was identified. Charts were reviewed for the following
      perioperative (intraoperative time plus recovery room time) events: time for
      extubation, duration of stay in the Postanesthesia Care Unit (PACU), and duration
      of stay in the hospital. Furthermore, any of the following complications were
      noted: electrocardiographic (ECG) changes, postoperative nausea and vomiting,
      hypotension, subjective reports of pain, decreasing oxygen saturation (SpO(2))
      levels, respiratory complications, postoperative fever, agitation in the PACU,
      and hypersomnolence in PACU. In addition, patient hospital stay and major
      morbidity and mortality during hospital stay were recorded. MAIN RESULTS: Ten
      patients pharmacologically treated for their narcolepsy symptoms that underwent
      27 noncardiac surgical procedures under general anesthesia. We found no evidence
      that the pharmacologically treated narcolepsy patients were at any increased risk
      for perioperative complications. Furthermore, their time for endotracheal
      extubation, length of stay in the PACU and hospital did not differ from
      nonnarcolepsy patients. CONCLUSION: Pharmacological therapy for narcolepsy should
      be continued during the perioperative period. In addition, treated narcolepsy
      patients are at no increased risk for postoperative complications.

PMID- 15721726
TI  - The esophageal-tracheal combitube resistance and ventilatory pressures.
AB  - STUDY OBJECTIVE: To measure resistance of the Combitube, a supraglottic
      ventilatory device used in the management of the patients with difficult airways,
      and its influence on delivered ventilatory pressures. DESIGN: Prospective study.
      SETTING: University-affiliated hospital. PATIENTS: A total of 20 patients with
      ASA status I or II who were scheduled for elective knee arthroscopy.
      INTERVENTIONS: (Part 2 of the study) After induction of general anesthesia and
      insertion of the Combitube, mechanical ventilation was initiated. Airway
      pressures were measured using fluid-filled pressure lines at the Y-piece (P(Y
      piece)) of the breathing system and in the oropharynx (P(oropharynx)) at a
      position 2 cm beyond the second proximal anterior hole of the Combitube. These
      pressures were simultaneously recorded and the pressure curves were compared.
      MEASUREMENTS: (Part 1 of the study) Resistance of the esophageal and the tracheal
      lumen of the 37-F Combitube and standard endotracheal tubes (with internal
      diameters of 6, 7, and 8 mm) was compared ex vivo with a Datex AS/3 monitor.
      Ventilation conditions were kept constant at a tidal volume of 0.5 L, frequency
      of 10 breaths per minute, and ramp flow waveform and peak flow of 1 L/s. MAIN
      RESULTS: Resistance of standard endotracheal tubes was inversely proportional to
      their diameters (16, 11, and 7 cm H(2)O/L per second for the tubes with internal
      diameters of 6, 7, and 8 mm, respectively). The resistance of the Combitube's
      tracheal lumen was 12 cm H(2)O/L per second. There was a significant difference
      in peak respiratory pressures between P(Y-piece) and P(oropharynx) (40 +/- 5 and
      23 +/- 5 cm H(2)O, respectively). CONCLUSIONS: The Combitube has significant
      airflow resistance that should be considered when patients are mechanically
      ventilated because the delivered oropharyngeal pressure is significantly lower
      than the pressure measured at the anesthesia breathing system.

PMID- 15721727
TI  - Antagonism of profound cisatracurium and rocuronium block: the role of objective
      assessment of neuromuscular function.
AB  - STUDY OBJECTIVE: The purpose of this study is to determine the incidence of
      significant (train-of-four [TOF] ratio <0.70), but clinically undetectable (TOF
      ratio >0.40), residual neuromuscular block after neostigmine antagonism of
      profound cisatracurium (CIS) or rocuronium (ROC) block. DESIGN: Prospective,
      randomized, open-label study. SETTING: University hospital. PATIENTS: Forty ASA
      physical status I and II undergoing elective surgical procedures. INTERVENTIONS:
      Anesthesia was induced with propofol 1.5 to 2.5 mg/kg IV plus fentanyl 2 to 4
      mug/kg and maintained with N(2)O/desflurane plus narcotic supplementation. The
      electromyographic response of the adductor pollicis was recorded. Train-of-four
      stimulation was given every 20 seconds. Twitch height (T1) and TOF fade ratio
      were continuously recorded. In group 1 (n = 20), neuromuscular block was induced
      with CIS 0.10 mg/kg, and T1 was maintained at 5% of control by a constant
      infusion of CIS until the end of surgery. One minute after the termination of the
      infusion, neostigmine 0.05 mg/kg was administered. T1 and TOF values were
      monitored continuously for the next 20 minutes. Group 2 (n = 20) is identical to
      group 1 except that the initial drug was ROC 0.60 mg/kg, and paralysis was
      maintained with an infusion of ROC. MEASUREMENTS AND MAIN RESULTS: There were no
      significant differences in the recovery patterns of CIS vs ROC. The duration
      (bolus to end of infusion) in both groups averaged 2.7 hours, and the mean
      cumulative dose of relaxant approximated 4 x the ED(95). T1 at the time of
      reversal was 6% (4%-10%) of control. Mean TOF ratios at 10, 15, and 20 minutes
      were 0.55, 0.71, and 0.0.81, respectively. Return to a TOF ratio >0.40 was always
      achieved in 15 minutes or less. However, at 20 minutes postreversal, 5 of 40
      subjects had TOF ratios <0.70 and only 11 individuals had recovered to a TOF
      ratio of 0.90 or greater. CONCLUSIONS: Most clinicians cannot detect tactile fade
      once the TOF ratio exceeds 0.40. When reversing profound block, an objective
      monitor of neuromuscular function is required if the extent of residual block is
      to be assessed with any confidence.

PMID- 15721729
TI  - Constant positive airway pressure reduces hypoventilation induced by inhalation
      anesthesia.
AB  - STUDY OBJECTIVE: To discover if reducing respiratory system impedance would
      increase tidal volume and improve ventilation during inhalation anesthesia.
      DESIGN: Prospective, randomized cross-over study. SUBJECTS: Nine ASA physical
      status I and II adult female oncology patients undergoing breast operations with
      or without lymph node dissection and general anesthesia while breathing
      spontaneously. INTERVENTIONS AND MEASUREMENTS: Patients underwent alternating
      trials of constant positive airway pressure, with or without pressure support.
      Constant positive airway pressure and pressure support were titrated to maximize
      respiratory system compliance and equal inspiratory pressure gradient across
      tracheal tube, respectively. Variables reflecting cardiovascular function,
      pulmonary mechanics and lung gas exchange, and respired gases and isoflurane
      concentrations were measured. MAIN RESULTS: End-tidal concentration of isoflurane
      (1.3 +/- 0.2%), Fio(2) (0.43 +/- 0.09 ), and CO(2) elimination (209 +/- 42 mL
      min(-1)) was unchanged throughout study in patients aged 63 +/- 12 years,
      weighing 72 +/- 12 kg. Constant positive airway pressure (12 +/- 2 cm H(2)O)
      increased respiratory system compliance from 52 +/- 8 to 80 +/- 9 mL cm H(2)O(-1)
      (P < .001), tidal volume from 156 +/- 32 to 325 +/- 52 mL (P < .001), and minute
      ventilation from 4.37 +/- 0.86 to 6.18 +/- 0.92 L min(-1) (P < .001). Respiratory
      rate decreased from 29 +/- 7 to 19 +/- 2 min(-1) (P < .001), Paco(2) decreased
      from 54 +/- 8 to 44 +/- 6 mm Hg (P < .001), and Pao(2) increased from 137 +/- 37
      to 160 +/- 64 mm Hg (P < .001). Pressure support (3.1 +/- 0.3 cm H(2)O) did not
      alter ventilation or gas exchange. CONCLUSION: We conclude that constant positive
      airway pressure titrated to optimal respiratory system compliance will increase
      efficiency of inspiratory muscles and improve ventilation. Constant positive
      airway pressure facilitates a pattern of breathing that minimizes some of the
      adverse pulmonary effects of inhalation anesthesia.

PMID- 15721728
TI  - Comparison of the effects of propofol and midazolam on the cardiovascular
      autonomic nervous system during combined spinal and epidural anesthesia.
AB  - STUDY OBJECTIVE: To investigate the effect of propofol and midazolam on cardiac
      autonomic nervous system (CANS) activity during combined spinal-epidural
      anesthesia. DESIGN: Prospective, clinical study. SETTING: Operating room of a
      university hospital. PATIENTS: Forty ASA physical status I and II patients
      scheduled for knee surgery. INTERVENTION: Patients were randomized to receive
      sedation with either propofol or midazolam. MEASUREMENTS: Heart rate (HR), HR
      variability (HRV), systolic arterial pressure (SAP), and SAP variability (SAPV)
      were used for the analysis. These values were measured at the preanesthetic
      period, after intrathecal injection for spinal anesthesia, after sedation with
      propofol or midazolam, and just before the end of surgery with sedation. Cross
      spectral analyses of the HR and SAP data were assessed to quantify the frequency
      related coherence spectra and phase spectra. MAIN RESULTS: Spinal anesthesia
      itself had no effect on power spectral changes in both groups. After sedation, as
      for HRV, high-frequency (HF) power (HF, 0.15-0.40 Hz) did not change, whereas low
      frequency (LF) power (LF, 0.04-0.15 Hz) and LF/HF, an indicator of CANS balance,
      significantly decreased with propofol. Further, coherence in cross-spectra
      presented depression in the LF band area after sedation with propofol. Before the
      end of surgery with sedation, LF and LF/HF in both HRV and SAPV were correlated
      with age in those with propofol; however, scarce relation was observed in those
      who received midazolam. CONCLUSIONS: Propofol was more potent than midazolam in
      causing CANS activity to be sympatholytic during combined spinal and epidural
      anesthesia and which was correlated with age only with propofol.

PMID- 15721730
TI  - Usefulness of routine preoperative testing: a prospective single-observer study.
AB  - STUDY OBJECTIVE: The purpose of this study is to determine whether routine
      preoperative testing has a usefulness not previously recognized in a small
      preliminary study to decide if such a hypothesis might be worthy of testing in a
      larger study. DESIGN: Single-observer, prospective, observational study. SETTING:
      Tertiary-care referral center in South India that performs 11 preoperative tests
      on each patient. PATIENTS: One hundred twenty-seven adult patients scheduled for
      elective neurosurgery. INTERVENTIONS: Patients were studied to determine whether
      outcome was influenced by laboratory tests, which were either indicated by health
      history elicited by a computerized rule-based questionnaire or unindicated by
      patient history. MEASUREMENT AND MAIN RESULTS: Of the 1395 tests performed
      preoperatively, 513 (36.8%) were indicated and 882 (63.3%) were unindicated. Of
      513 indicated tests, 17 (3.3%) prompted changes in patient care; 8 (0.91%) of 882
      unindicated tests (P < .001) prompted changes in care. All patients with anemia,
      significant electrocardiographic abnormalities, or HIV infection were detected by
      the computerized questionnaire. Among the changes in care prompted by unindicated
      tests, 4 patients received diabetic therapy or counseling, and 4 patients with
      abnormal silhouettes on chest radiograph had nonbeneficial echocardiography. Only
      screening for diabetes seemed to have usefulness as a routine preoperative test
      in this patient population. CONCLUSION: Although the incidence of unindicated
      preoperative screening tests is still more than 50%, no previously unidentified
      benefit was found to support this persistence of unwarranted testing. The limited
      number of patients in this study necessitates a larger study to ensure greater
      certainty before such a recommendation is made to the public. If similar results
      in another but larger study involving similar design, simple changes in the
      system of preoperative care may save the health care system the considerable
      expense of unwarranted testing.

PMID- 15721731
TI  - Oral multidose caffeine-paracetamol combination is not effective for the
      prophylaxis of postdural puncture headache.
AB  - STUDY OBJECTIVES: To investigate the effects of different doses of oral caffeine
      paracetamol combinations in postdural puncture headache (PDPH) prophylaxis.
      DESIGN: Prospective, randomized, placebo-controlled, blinded study. SETTING:
      University hospital. PATIENTS: A total of 210 ASA physical status I and II
      patients undergoing lower extremity surgery. INTERVENTIONS: Patients were
      randomly divided into 3 groups. One hour before the spinal anesthesia, the first
      group (n = 70) received placebo, the second group (n = 70) received 500-mg
      paracetamol + 75-mg caffeine, and the third group (n = 70) received 500-mg
      paracetamol + 125-mg caffeine orally. The same doses were repeated every 6 hours
      for 3 days. Patients were then interviewed on days 1, 2, 3, 4, and 7 to inquire
      about any PDPH. The interviewer was unaware of the PDPH prophylaxis group
      members. Patients who were discharged early were interviewed by telephone.
      MEASUREMENTS AND MAIN RESULTS: Postdural puncture headache occurred in 11
      patients (15.7%) in group 1, 10 patients (% 14.28) in group 2, and 10 patients (%
      14.28) in group 3. The differences between the groups were insignificant (P >
      .05). The complications due to spinal anesthesia were similar in the 3 groups.
      Side effects of caffeine such as lack of sleep, tachycardia, and hypertension
      were not observed in groups 2 or 3. CONCLUSIONS: Prophylactic administration of
      paracetamol-caffeine combinations at the stated doses does not prevent PDPH.

PMID- 15721732
TI  - The effectiveness of rescue antiemetics after failure of prophylaxis with
      ondansetron or droperidol: a preliminary report.
AB  - STUDY OBJECTIVES: To compare the effectiveness of treating established
      postoperative nausea and vomiting (PONV) with an antiemetic acting at a different
      receptor with that of treating PONV with the antiemetic used for prophylaxis.
      DESIGN: Analysis of data collected in a previously published randomized, double
      blind, placebo-controlled study. SETTING: Outpatient surgical procedures from 50
      institutions in North America. PATIENTS: Patients (N = 2061) undergoing
      outpatient surgical procedures planned to last no more than 2 hours.
      INTERVENTIONS: Patients were randomized to receive ondansetron 4 mg, droperidol
      1.25, droperidol 0.625 mg, or placebo. In the postoperative anesthesia care unit,
      patients who developed PONV received rescue antiemetics at the discretion of the
      attending anesthesiologist. The following antiemetics were used for rescue:
      ondansetron 4 mg, droperidol 0.625 to 1.25 mg, metoclopramide 10 mg, promethazine
      6.25 to 25 mg, and dimenhydrinate 25 to 50 mg. MEASUREMENTS: The complete
      response rate (no nausea, no emesis, and no need for further rescue) after
      administration of the rescue antiemetic in patients with established PONV was
      calculated. The complete response rate after administration of each of the
      different rescue antiemetics was compared with that after administration of the
      same antiemetic used for PONV prophylaxis. MAIN RESULTS: In patients who failed
      prophylaxis with ondansetron 4 mg, the complete response rate was significantly
      higher (P = .02) after rescue with promethazine 6.25 to 25 mg (78%) than after
      rescue with ondansetron 4 mg (46%). In patients who failed prophylaxis with
      droperidol 0.625 and 1.25 mg, the complete response rate was significantly higher
      after rescue with promethazine 6.25 to 25 mg (77%; P = .02) and dimenhydrinate 25
      to 50 mg (78%; P = .04) than after rescue with droperidol 0.625 to 1.25 mg (56%).
      CONCLUSION: In patients who failed prophylaxis with ondansetron or droperidol,
      promethazine was significantly more effective than the agent used for prophylaxis
      for the treatment of PONV. In patients who failed prophylaxis with droperidol,
      dimenhydrinate was also more effective than droperidol for the treatment of
      established PONV in the postoperative anesthesia care unit.

PMID- 15721733
TI  - An unusual presentation of idiopathic thrombocytopenic purpura in pregnancy.
AB  - A 35-year-old, 39-week pregnant woman underwent an uneventful emergent cesarean
      delivery for suspected placental abruption or uterine dehiscence. Given the
      urgency of the situation and the unremarkable airway anatomy, general anesthesia
      was the chosen technique. Four hours after her surgery, she returned to the
      operating room for persistent vaginal bleeding. Hematology tests performed before
      the cesarean delivery revealed severe thrombocytopenia. This was later diagnosed
      as idiopathic thrombocytopenia, which was treated successfully with steroid
      therapy.

PMID- 15721734
TI  - Fluoroscopic imaging for technically difficult spinal anesthesia.
AB  - We report a case of technically difficult spinal anesthesia in a morbidly obese
      woman, which was successfully implemented under fluoroscopy. Although
      radiological imaging is well known to guide various regional anesthetic
      procedures, until now, the utility of fluoroscopic imaging to facilitate spinal
      anesthesia had not been reported.

PMID- 15721735
TI  - Coronary vasospasm leading to an acute myocardial infarction after the
      administration of dolasetron.
AB  - The 5-hydroxytryptamine antagonists are commonly used agents for the treatment of
      postoperative nausea and vomiting. However, these drugs can have significant
      cardiovascular adverse effects. We report a case of acute myocardial infarction
      after administration of dolasetron in a 17-year-old adolescent girl during
      strabismus corrective surgery.

PMID- 15721736
TI  - Listening to the patient: potential medical battery in oral intubation.

PMID- 15721737
TI  - Development: edging towards circuitry, behavior and disease.

PMID- 15721738
TI  - SOX genes and neural progenitor identity.
AB  - Resident among the highly structured adult nervous system, a few cells, referred
      to as neural progenitors or stem cells, maintain the ability to self-renew or
      differentiate. From the time of their specification during neural induction and
      throughout the building of the nervous system, neural progenitor cells preserve
      their broad developmental potential and replicative capacity to be able to
      produce the vast array of neuronal and glial cell types of the mature nervous
      system as, and when, required. Recently, considerable attention has been focused
      on identifying the molecular mechanisms responsible for maintaining neural
      progenitor or stem cell fate throughout ontogeny. The expression of a subset of
      SOX transcription factors is initiated concomitant with the acquisition of neural
      progenitor identity and is then maintained in the entire progenitor population of
      the developing and adult nervous system. Strikingly, studies in the central and
      peripheral nervous system of chick and mouse have revealed that SOX factors are
      key regulators of neural progenitor identity, promoting self-renewal in a context
      dependent manner by sustaining the undifferentiated state of progenitor cells and
      maintaining their ability to either proliferate or differentiate.

PMID- 15721739
TI  - Development of circuits that generate simple rhythmic behaviors in vertebrates.
AB  - Neurobiologists have long sought to understand how circuits in the nervous system
      are organized to generate the precise neural outputs that underlie particular
      behaviors. Given the complexity of the nervous system in higher vertebrates this
      is a daunting task. Nevertheless, recent advances in developmental genetics hold
      out hope that studies of locomotor and respiratory circuits will provide general
      insight for understanding how ensembles of neurons are wired to control specific
      behaviors.

PMID- 15721740
TI  - Transcriptional control of cognitive development.
AB  - Cognitive development is determined by both genetics and environment. One point
      of convergence of these two influences is the neural activity-dependent
      regulation of programs of gene expression that specify neuronal fate and
      function. Human genetic studies have linked several transcriptional regulators to
      neurodevelopmental disorders including mental retardation and autism spectrum
      disorders. Recent reports on two such factors, CREB-binding protein and methyl
      CpG-binding protein 2, have begun to reveal how epigenetics and neuronal activity
      act to modulate the program of gene expression required for synaptic development
      and function.

PMID- 15721741
TI  - Radial 'glial' progenitors: neurogenesis and signaling.
AB  - Cells with radial morphology in the developing brain were first identified more
      than 100 years ago. These cells, later termed radial glia, have been studied
      primarily as migratory scaffolds and glial progenitors. However, it has become
      increasingly clear, on the basis of in vitro studies and more recent in vivo fate
      mapping experiments, that radial glia also generate neurons during embryonic
      development. Now the challenge will be to understand the signaling events that
      regulate the spatial and temporal heterogeneity of these cells and their
      developmental potential. Recent work has identified the Notch, ErbB, and
      fibroblast growth factor signaling pathways as central to the regulation of
      radial 'glial' progenitors.

PMID- 15721742
TI  - Neuron-glia interaction in the insect nervous system.
AB  - In all complex organisms, glial cells are pivotal for neuronal development and
      function. Insects are characterized by having only a small number of these cells,
      which nevertheless display a remarkable molecular diversity. An intricate
      relationship between neurons and glia is initially required for glial migration
      and during axonal patterning. Recent data suggest that in organisms such as
      Drosophila, a prime role of glial cells lies in setting boundaries to guide and
      constrain axonal growth.

PMID- 15721743
TI  - Long-distance retrograde neurotrophic signaling.
AB  - The retrograde communication of neurotrophic signals from axon terminals to
      neuron cell bodies is crucial for neuron survival and plasticity. Several
      mechanisms have been proposed in the past, but recent evidence strongly supports
      the hypothesis that the retrograde propagation of self-regenerating signaling
      organelles, derived from the endocytosis of activated neurotrophin-bound receptor
      tyrosine kinases, is the primary mechanism responsible for this long-distance
      communication.

PMID- 15721744
TI  - p75NTR--live or let die.
AB  - During neuronal development, neurotrophins are essential factors that promote
      survival, differentiation and myelination of neurons. The trophic signals are
      relayed to the cells via binding to Trk receptor tyrosine kinases and the p75
      neurotrophin receptor. Paradoxically, the p75 neurotrophin receptor also ensures
      rapid and appropriate apoptosis of neonatal neurons not reaching their proper
      targets and transmits death signals to injured neurons. Until recently, the
      mechanisms by which the p75 neurotrophin receptor governs these opposing
      functions have remained elusive. By the identification of new ligands and
      cytosolic interacting partners, receptor cleavage products and coreceptors, some
      of these mechanisms are now being unraveled. Here, we review recent progress in
      delineating the molecular networks that enable p75(NTR) to dictate life and
      death.

PMID- 15721745
TI  - Probing microtubule +TIPs: regulation of axon branching.
AB  - Axon branching is vital to the development of a highly interconnected and
      functional nervous system. Similar to axon growth and guidance, axon branching is
      subject to dynamic remodeling of the neuronal cytoskeleton. Coordinated
      remodeling of the cytoskeleton is achieved through parallel and direct targeting
      of both actin filaments and a subset of highly dynamic microtubules that probe
      the actin-rich peripheral domains in growth cones and emerging branch sites. A
      growing number of extracellular cues implicated in growth cone guidance also
      influence axon branch behavior. Mechanistic insight into the molecular basis of
      growth cone steering and axon branching reveals significant similarities but also
      uncovers important differences between these crucial events in the establishment
      of neural circuits.

PMID- 15721746
TI  - Growth of dendritic spines: a continuing story.
AB  - Dendritic spines, which are present at the vast majority of excitatory synapses
      in the central nervous system, have a specialized cytoskeleton of dynamic actin
      filaments that makes them capable of rapid morphological plasticity. During
      development, structural remodeling of nascent spines is an important factor in
      experience-dependent shaping of neuronal circuits, whereas in the adult brain
      spines maintain a balance between morphological stability and plasticity.

PMID- 15721747
TI  - Cadherins and catenins in synapse development.
AB  - Cadherin-catenin complexes have been well established as key regulators of cell
      adhesion. Recent work has elucidated a pivotal role for these molecules in
      synaptic assembly, remodelling and plasticity. Far from being mere adhesive
      scaffolds, cadherins might directly regulate cell signalling to modulate synaptic
      connectivity.

PMID- 15721748
TI  - Wired on hormones: endocrine regulation of hypothalamic development.
AB  - The hormones that regulate the hypothalamic circuits that control essential
      functions, such as reproduction and energy homeostasis, also specify brain
      architecture by regulating key developmental events. The cellular mechanisms
      underlying the developmental actions of testosterone and estrogen to determine
      patterns of neuronal cell death, synaptogenesis and axon guidance are being
      identified. Recent neuroanatomical evidence indicates that the adipocyte-derived
      hormone leptin may direct the development of hypothalamic pathways involved in
      energy homeostasis by promoting axonal projections from the arcuate nucleus of
      the hypothalamus to other hypothalamic sites that mediate the effects of leptin
      on food intake and body weight. Understanding how sex steroids and leptin
      regulate hypothalamic development will enable us to identify hormonally directed
      signaling events essential to the specification of neural circuitry that is
      optimized for sustained homeostasis.

PMID- 15721749
TI  - Development of central pattern generating circuits.
AB  - The networks that generate rhythmic motor patterns in invertebrates and
      vertebrates are ideal for studying the mechanisms by which functional circuits
      are formed during development. Rhythmic motor patterns and movements are seen
      embryonically, before they are needed for behavior; recent work suggests that
      activity in immature spinal cord networks is important for circuit formation and
      transmitter specification. Despite significant advances in describing the
      patterns of transcription factor expression in both invertebrate nervous systems
      and vertebrate spinal cord, a real understanding of how central pattern
      generators develop is hindered by our lack of knowledge of the organization of
      these circuits in adults.

PMID- 15721750
TI  - A precritical period for plasticity in visual cortex.
AB  - One of the seminal discoveries in developmental neuroscience is that altering
      visual experience through monocular deprivation can alter both the physiological
      and the anatomical representation of the two eyes, called ocular dominance
      columns, in primary visual cortex. This rearrangement is restricted to a critical
      period that starts a few days or weeks after vision is established and ends
      before adulthood. In contrast to the original hypothesis proposed by Hubel and
      Wiesel, ocular dominance columns are already substantially formed before the
      onset of the critical period. Indeed, before the critical period there is a
      period of ocular dominance column formation during which there is robust
      spontaneous activity and visual experience. Recent findings raise important
      questions about whether activity guides ocular dominance column formation in this
      'precritical period'. One developmental event that marks the passage from the
      precritical period to the critical period is the activation of a GABAergic
      circuit. How these events trigger the transition from the precritical to critical
      period is not known.

PMID- 15721751
TI  - Phagocytosis in the developing CNS: more than clearing the corpses.
AB  - Cell corpses generated during CNS development are eliminated through phagocytosis
      performed by a variety of cells, including mesenchyme-derived macrophages and
      microglia, or glial cells originating in the neurogenic ectoderm. Mounting
      evidence indicates that in different species, phagocytes not only clear cell
      corpses but also engulf still-living neural cells or axons, and thereby promote
      cell death or axon pruning. Knowledge of the mechanisms of corpse recognition by
      engulfing cells provides molecular signals to this new role for phagocytes. These
      observations support a conserved and instructive role for phagocytosis in the
      execution of regressive events during neurogenesis.

PMID- 15721752
TI  - Guidance of vascular and neural network formation.
AB  - Blood vessels and nerves are structurally similar complex branched systems. Their
      guidance must be exquisitely regulated to ensure proper wiring of both networks.
      Recent results showed that specialized endothelial cells, resembling axonal
      growth cones, form the tips of growing capillaries. These endothelial tip cells
      guide outgrowing capillaries in response to gradients of extracellular matrix
      bound vascular endothelial growth factor. Several axon guidance molecules,
      including Semaphorins, Netrins, Ephrins and Slits, have also been implicated in
      vessel pathfinding and network formation. In particular, Semaphorin3E and its
      receptor plexinD1 in addition to the Netrin receptor UNC5B have recently been
      shown to direct endothelial tip cell navigation.

PMID- 15721753
TI  - Chondroitin sulfate proteoglycans in neural development and regeneration.
AB  - Proteoglycans are of two main types, chondroitin sulfate (CSPGs) and heparin
      sulfate (HSPGs). The CSPGs act mainly as barrier-forming molecules, whereas the
      HSPGs stabilise the interactions of receptors and ligands. During development
      CSPGs pattern cell migration, axon growth pathways and axon terminations. Later
      in development and in adulthood CSPGs associate with some classes of neuron and
      control plasticity. After damage to the nervous system, CSPGs are the major axon
      growth inhibitory component of the glial scar tissue that blocks successful
      regeneration. CSPGs have a variety of roles in the nervous system, including
      binding to molecules and blocking their action, presenting molecules to cells and
      axons, localising active molecules to particular sites and presenting growth
      factors to their receptors.

PMID- 15721754
TI  - Young and excitable: the function of new neurons in the adult mammalian brain.
AB  - Adult neurogenesis occurs in most species and is regulated by a wide variety of
      environmental and pharmacological challenges. The functional integration of
      neurons generated in the adult was first demonstrated in songbirds more than two
      decades ago. In the adult mammalian brain, neurons are continuously generated in
      two structures, the olfactory bulb and the hippocampus. Current evidence suggests
      that adult-born immature neurons have distinct electrophysiological properties
      from old neurons, and proposed roles in a variety of functions including
      olfaction, learning and mood regulation.

PMID- 15721755
TI  - Preparation of highly specific radioactivity [18F]flumazenil and its evaluation
      in cynomolgus monkey by positron emission tomography.
AB  - A straightforward method for the preparation of no-carrier-added (n.c.a.)
      [18F]flumazenil via standard nucleophilic radiofluorination of the corresponding
      nitro-analog Ro 15-2344 has been developed. The labeling was performed by
      employing the K18F/kryptofix complex in DMF at 160 degrees C for 30 min and
      equimolar ratio [K/K2.2.2]+18F-/precursor. Under these conditions, an 18F
      incorporation rate into flumazenil was in the range of 55-60%. The final product
      was isolated by HPLC purification within a total synthesis time of 75 min and a
      radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere
      autoradiography of brain sections demonstrated selective uptake of the
      radioligand in the areas of high density of the central benzodiazepine receptors
      (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC
      demonstrated similar results by [18F]flumazenil as for [11C]flumazenil. In
      blocking experiments, almost all radioactivity was inhibited by the addition of
      unlabeled flumazenil. [18F]Flumazenil is a suitable radioligand for PET
      assessment of the BZR.

PMID- 15721756
TI  - Production, processing and small animal PET imaging of titanium-45.
AB  - INTRODUCTION: Titanium-45 was prepared as a tool for elucidation of the mechanism
      of action of titanium anticancer drugs in vivo using microPET imaging. METHODS:
      Titanium-45 was produced by the 45Sc(p,n)45Ti nuclear reaction using 14.5 MeV
      protons. Sufficient yields of 45Ti were produced and separated from the target
      material with 99.8% radionuclidic purity using a simple, efficient separation
      procedure. RESULTS: A typical bombardment of 5 microA for 1 h produced an average
      of 2105+/-150 MBq (56.9+/-4.0 mCi) at the end of bombardment (EOB), well within
      acceptable range of the calculated theoretical yields of 2165 MBq and 433 MBq
      microA-1 h-1 (58.5 mCi and 11.7 mCi microA-1 h-1). This amount of activity is
      sufficient for the radiosynthesis of target compounds as well as imaging studies.
      MicroPET images of a miniature Derenzo phantom show excellent resolution where
      rods of 1.25 mm were separated by four times their diameter. CONCLUSIONS:
      Titanium-45 can be easily produced on a biomedical cyclotron with excellent
      yields as compared to calculated theoretical values with imaging studies
      demonstrating that the decay properties of titanium-45 are well suited for
      microPET.

PMID- 15721757
TI  - Regional distribution of serotonin transporter protein in postmortem human brain:
      is the cerebellum a SERT-free brain region?
AB  - INTRODUCTION: The primary approach in assessing the status of brain serotonin
      neurons in human conditions such as major depression and exposure to the illicit
      drug ecstasy has been the use of neuroimaging procedures involving radiotracers
      that bind to the serotonin transporter (SERT). However, there has been no
      consistency in the selection of a "SERT-free" reference region for the estimation
      of free and nonspecific binding, as occipital cortex, cerebellum and white matter
      have all been employed. OBJECTIVE AND METHODS: To identify areas of human brain
      that might have very low SERT levels, we measured, by a semiquantitative Western
      blotting procedure, SERT protein immunoreactivity throughout the postmortem brain
      of seven normal adult subjects. RESULTS: Serotonin transporter could be
      quantitated in all examined brain areas. However, the SERT concentration in
      cerebellar cortex and white matter were only at trace values, being approximately
      20% of average cerebral cortex and 5% of average striatum values. CONCLUSION:
      Although none of the examined brain areas are completely free of SERT, human
      cerebellar cortex has low SERT binding as compared to other examined brain
      regions, with the exception of white matter. Since the cerebellar cortical SERT
      binding is not zero, this region will not be a suitable reference region for SERT
      radioligands with very low free and nonspecific binding. For SERT radioligands
      with reasonably high free and nonspecific binding, the cerebellar cortex should
      be a useful reference region, provided other necessary radioligand assumptions
      are met.

PMID- 15721758
TI  - Potential of [11C]DASB for measuring endogenous serotonin with PET: binding
      studies.
AB  - The serotonin transporter radioligand [11C]-3-amino-4-(2
      dimethylaminomethylphenylsulfanyl)-benzonitrile, or [11C]DASB, was examined in
      order to assess its potential for measuring fluctuations in endogenous serotonin
      concentrations with positron emission tomography. Binding characteristics of
      [11C]DASB and the propensity for serotonin to displace the tracer were explored
      in rat brain homogenates. Experiments showed that serotonin displaced [11C]DASB
      in vitro. Ex vivo experiments performed after tranylcypromine injection (3 or 15
      mg/kg) showed a dose-dependent trend in radioactivity uptake and suggested that
      serotonin may compete with [11C]DASB for transporter binding.

PMID- 15721759
TI  - Radioiodinated phenylalanine derivatives to image pancreatic cancer: a
      comparative study with [18F]fluoro-2-deoxy-D-glucose in human pancreatic
      carcinoma xenografts and in inflammation models.
AB  - This work validated an in vivo model of human pancreatic cancer for preclinical
      studies and evaluated p-amino-3-[123I]iodo-L-phenylalanine (AIPA) and p
      [123I]iodo-L-phenylalanine (IPA) as potential imaging agents for pancreatic
      cancer. The primary human pancreatic adenocarcinoma PaCa44 and PanC1 cells (1.5
      2.5x10(6)) were inoculated either subcutaneously into the flank or orthotopically
      into the pancreas of severe combined immunodeficient (SCID) mice. Tumor formation
      was recorded by palpation and monitored by magnetic resonance imaging (MRI).
      After intravenous injection, tumor affinity and organ distribution of AIPA and
      IPA were compared with those of [18F]fluoro-2-deoxy-D-glucose (FDG) in tumor
      bearing SCID mice and in concanavalin A (ConA)-induced inflammation models. All
      SCID mice developed a pancreatic tumor 2-4 weeks after cell implantation. All
      subcutaneously transplanted tumors were detected by MRI and confirmed
      histologically, whereas 90% and 68% of the histopathologically confirmed
      orthotopic PaCa44 and PanC1 tumors were accurately demonstrated by MRI. Tumor
      formation and spread after orthotopic implantation showed invasion into adjacent
      organs and metastases in different sites of the abdomen. In contrast, no organ
      invasion or metastases were demonstrated by subcutaneous implantation. In vivo,
      AIPA and IPA displayed high affinity for pancreatic tumors. Radioactivity uptake
      into a tumor at 60 and 240 min amounted to 7.2+/-2.1% and 10.7+/-2.5% I.D./g for
      AIPA and 13.3+/-3.5% and 15.2+/-3.8% I.D./g for IPA in heterotopic tumors as
      compared with 11.8+/-3.2% and 15.2+/-2.4% I.D./g for AIPA and 16.7+/-3.5% and
      22.5+/-4.3% I.D./g for IPA in orthotopically implanted tumors. In comparison, the
      FDG uptake was 10.8+/-2.9% and 2.5+/-0.6% I.D./g into heterotopic tumors and
      12.5+/-3.8% and 3.5+/-1.2% I.D./g into the orthotopic ones at 60 and 240 min
      postinjection. The FDG uptake markedly increased (>400%) in the area of
      inflammation, whereas accumulation of AIPA and IPA in inflammation remained
      moderate and comparable with that determined in muscle. In summary, the
      orthotopic implantation model, more than the heterotopic one, reflects more
      closely the clinical course of the disease, thus representing the appropriate in
      vivo model for preclinical studies. The specific and high-level targeting of AIPA
      and IPA to human pancreatic tumor xenografts, with marked tumor-to-background
      ratios, indicate that AIPA and IPA are interesting candidates as radiotracers for
      noninvasive imaging of pancreatic cancer. IPA has the advantage of relatively low
      renal uptake and thus presents as the most promising candidate.

PMID- 15721760
TI  - Investigation into 64Cu-labeled Bis(selenosemicarbazone) and
      Bis(thiosemicarbazone) complexes as hypoxia imaging agents.
AB  - BACKGROUND: Cu-diacetyl-bis(N4-methylthiosemicarbazone) [Cu-ATSM], although
      excellent for oncology applications, may not be suitable for delineating
      cardiovascular or neurological hypoxia. For this reason, new Cu hypoxia positron
      emission tomography (PET) imaging agents are being examined to search for a
      higher selectivity for hypoxic or ischemic tissue at higher oxygen concentrations
      found in these tissues. Two approaches are to increase alkylation or to replace
      the sulfur atoms with selenium, resulting in the formation of
      selenosemicarbazones. METHODS: Three 64Cu-labeled selenosemicarbazone complexes
      were synthesized and one was screened for hypoxia selectivity in vitro using EMT
      6 mouse mammary carcinoma cells. Rodent biodistribution and small animal PET
      images were obtained from BALB/c mice implanted with EMT-6 tumors. One alkylated
      thiosemicarbazone was synthesized and examined. RESULTS: Of the three
      bis(selenosemicarbazone) ligands synthesized and examined, only 64Cu-diacetyl
      bis(selenosemicarbazone) [64Cu-ASSM] was isolated in high-enough radiochemical
      purity to undertake cell uptake experiments where uptake was shown to be
      independent of oxygen concentration. The bis(thiosemicarbazone) complex
      synthesized, 64Cu-diacetyl-bis(N4-ethylthiosemicarbazone) [64Cu-ATSE], showed
      hypoxia selectivity similar to 64Cu-ATSM although at a higher oxygen
      concentration. Biodistribution studies for 64Cu-ASSM and 64Cu-ATSE showed high
      tumor uptake at 20 min (64Cu-ASSM, 10.33+/-0.78% ID/g; 64Cu-ATSE, 7.71+/-0.46%
      ID/g). PET images of EMT-6 tumor-bearing mice visualized the tumor with 64Cu-ATSE
      and revealed hypoxia selectivity consistent with the in vitro data. CONCLUSION:
      Of the compounds synthesized, only 64Cu-ASSM and 64Cu-ATSE could be examined in
      vitro and in vivo. Although the stability of bis(selenosemicarbazone) complexes
      increased upon addition of methyl groups to the diimine backbone, the fully
      alkylated species, 64Cu-ASSM, demonstrated no hypoxia selectivity. However, the
      additional alkylation present in Cu-ATSE modifies the hypoxia selectivity and in
      vivo properties when compared with Cu-ATSM.

PMID- 15721761
TI  - The in vivo characteristics of genetically engineered divalent and tetravalent
      single-chain antibody constructs.
AB  - Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated
      to exhibit rapid blood clearance and better tumor penetration. To understand the
      short plasma half-life of multivalent single-chain antibody fragments, the
      pharmacokinetic properties of covalent dimeric scFv [sc(Fv)2], noncovalent
      tetrameric scFv {[sc(Fv)2]2} and IgG of MAb CC49 were examined. The scFvs
      displayed an ability to form higher molecular aggregates in vivo. A specific
      proteolytic cleavage of the linker sequence of the covalent dimeric or a
      deterioration of the noncovalent association of the dimeric scFv into tetravalent
      scFv constructs was not observed. In conclusion, sc(Fv)2 and [sc(Fv)2]2 are
      stable in vivo and have significant potential for diagnostic and therapeutic
      applications.

PMID- 15721762
TI  - Assessment of Tc-99m sestamibi tumor tissue uptake under the influence of
      increased arterial oxygen saturation.
AB  - The aim of this study is to investigate the potential effect of increased
      arterial saturation of oxygen in the magnitude of technetium-99m-hexakis-isobutyl
      isonitrile (99mTc-MIBI) uptake in tumor tissue and to compare the results with
      those of conventional 99mTc-MIBI tumor imaging in the same patient with lung
      cancer. A total of 26 lung cancer patients underwent initial SPECT (I-SPECT) and
      after oxygen inhalation SPECT (O2-SPECT). The early (ER) and delayed ratios (DR)
      of O2-SPECT mean+/-S.D. were significantly higher than those of I-SPECT mean+/
      S.D. (2.07+/-0.57 vs. 1.90+/-0.48 and 2.02+/-0.45 vs. 1.83+/-0.39, respectively).
      There are increased rates for the relative tumor uptake of 99mTc-MIBI by 9% for
      ER and 10% for DR on the O2-SPECT compared to I-SPECT. We found that 99mTc-MIBI
      uptake increased significantly in the tumor tissue with O2-SPECT compared to I
      SPECT. In conclusion, 99mTc-MIBI scintigraphy is one of the main methods for
      differentiating viable and nonviable tissue fractions in tumors. We consider that
      99mTc-MIBI uptake increase after oxygen inhalation is an indicator of positive
      acute cellular response of the tumor tissue to the rising tissue oxygen level.

PMID- 15721763
TI  - Biphenyls labeled with technetium 99m for imaging beta-amyloid plaques in the
      brain.
AB  - Formation and accumulation of excess aggregates of beta-amyloid (Abeta) plaques
      in the brain are critical factors contributing to the development and progression
      of Alzheimer's disease (AD). There is an urgent need for in vivo imaging agents
      that can specifically demonstrate the location and density of Abeta plaques in
      the brain. The aim of this study was to develop potential technetium 99m (99mTc)
      labeled diagnostic imaging agents specific for the detection of Abeta plaques.
      Based on previously obtained Abeta plaque-specific biphenyls containing a p-N, N
      dimethylaminophenyl group, a series of 99mTc and Re-N2S2-biphenyl derivatives was
      prepared. The stable neutral and lipophilic 99mTc complexes, [99mTc]19 and
      [99mTc]23, A+B, were successfully obtained. As surrogates for the 99mTc
      complexes, the corresponding surrogates, Re complexes of 23, were also prepared.
      Surprisingly, it was found that the Re complexes showed distinctively different
      retention profiles as compared with the corresponding 99mTc complexes.
      Biodistribution studies indicated that [99mTc]23A readily passed through the
      blood-brain barrier (1.18% dose/brain at 2 min) in contrast to the low brain
      penetration of [99mTc]19 (0.29% dose/brain at 2 min). Initial results suggested
      that [99mTc]23A showed selective binding to the Abeta plaque-like structures in
      the brain sections from transgenic mice but not in the postmortem human brain
      tissue of patients with confirmed AD. The results provide encouraging evidence
      that development of a 99mTc-labeled agent for imaging Abeta plaques in the brain
      may be feasible. Caution should be taken when comparing these 99mTc complexes
      with the corresponding surrogates--the Re complexes.

PMID- 15721764
TI  - Synthesis and evaluation of 2-[18F]fluoro-CP-118,954 for the in vivo mapping of
      acetylcholinesterase.
AB  - 5,7-Dihydro-3-[2-[1-(2-fluorobenzyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2,f]-1,2
      benzisoxazol-6-one (2-flouro-CP-118,954; 1), a potent acetylcholinesterase (AChE)
      inhibitor, was prepared as a radioligand by reductive alkylation of CP-144,885
      the debenzylated form of CP 118,954, with 2-[18F]fluorobenzaldehyde. The decay
      corrected radiochemical yield was 25-30% and the effective specific activity was
      41-53 GBq/micromol. Tissue distribution studies of 2-[18F]fluoro-CP-118,954
      ([18F]1) in mice showed that the regional brain distribution correlated well with
      the known density of AChE in the mouse brain. A high level of uptake in the
      striatum was also shown at all time points in the olfactory tubercle, which is
      known to have dopaminergic neurons. Blocking studies showed that radioligand
      uptake in all brain regions was not altered by either the dopamine receptor
      antagonists or the sigma receptor agonist. On the other hand, radioligand uptake
      in both the striatum and the olfactory tubercle was significantly blocked (80%)
      by ligand 1. The low level of bone uptake over time suggested that [18F]1
      underwent little in vivo metabolic defluorination. The lack of metabolite
      formation in the mouse brain indicated that the regional distribution was
      attributed to [18F]1. These results demonstrated that [18F]1 binds specifically
      and selectively to AChE in mice and appears to be a suitable radioligand for the
      in vivo mapping of AChE.

PMID- 15721765
TI  - In vivo evaluation of [123I]-4-iodo-N-(4-(4-(2-methoxyphenyl)-piperazin-1
      yl)butyl)-benzamide: a potential sigma receptor ligand for SPECT studies.
AB  - In this study, in vivo evaluation in mice and rabbits of [123I]-4-iodo-N-(4-(4-(2
      methoxyphenyl)-piperazin-1-yl)butyl)-benzamide ([123I]-BPB), a potential
      radioligand for visualisation of the sigma receptor by single photon emission
      computed tomography (SPECT), is reported. The compound possesses appropriate
      lipophilicity (log P=2.2) and binds sigma-1 and sigma-2 receptors (pKi=6.51 and
      6.79, respectively). In mice, this new radioiodinated tracer exhibited high brain
      uptake (4.99% ID/g tissue at 10 min postinjection) and saturable binding (3.06%
      ID/g tissue at 10 min postinjection) as determined by pretreatment with unlabeled
      [123I]-BPB. A metabolite study demonstrated no (less than 5%) labeled metabolites
      in the brain. In rabbits, regional brain distribution was investigated and the
      tracer displayed high, homogeneous central nervous system uptake. Selectivity was
      assessed by competition experiments with known sigma ligands. Metabolite analysis
      showed no (less than 8%) labeled metabolites in the rabbit brain. In conclusion,
      our findings indicate that [123I]-BPB is not a suitable tracer for visualisation
      of D3 receptors while its potential for sigma receptor imaging is severely
      hampered by its affinity for dopamine receptors.

PMID- 15721766
TI  - Synthesis and evaluation of inhaled [11C]butane and intravenously injected
      [11C]acetone as potential radiotracers for studying inhalant abuse.
AB  - The phenomenon of inhalant abuse is a growing problem in the US and many
      countries around the world. Yet, relatively little is known about the
      pharmacokinetic properties of inhalants that underlie their abuse potential.
      While the synthesis of 11C-labeled toluene, acetone and butane has been proposed
      in the literature, none of these compounds has been developed as radiotracers for
      PET studies. In the present report we extend our previous studies with
      [11C]toluene to include [11C]acetone and [11C]butane with the goal of comparing
      the pharmacokinetic profiles of these three volatile abused substances. Both
      [11C]toluene and [11C]acetone were administered intravenously and [11C]butane was
      administered via inhalation to anesthesized baboons. Rapid and efficient uptake
      of radiolabeled toluene and acetone into the brain was followed by fast clearance
      in the case of toluene and slower kinetics in the case of acetone. [11C]Butane
      was detected in the blood and brain following inhalation, but the levels of
      radioactivity in both tissues dropped to half of the maximal values over the
      period of less than a minute. To our knowledge, this is the first reported study
      of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman
      primates. These data provide insight into the pharmacokinetic features possibly
      associated with the abuse liability of toluene, acetone and butane.

PMID- 15721767
TI  - From gene to protein: a review of new and enabling technologies for multi
      parallel protein expression.
AB  - In the post-genomic era, increasingly greater demands and expectations are being
      placed on protein production laboratories to produce more proteins and in faster
      timelines. This has been coupled with an exponential increase in the number of
      requests for the production of proteins which lack structural and functional
      information. No longer can groups use literature available in the public domain
      solely to drive their expression strategy, and moreover current expression and
      concomitant purification strategies clearly do not meet modern-day demands for
      protein production. This review will therefore attempt to provide a definitive
      review of current 'best in class' cloning, expression and purification systems,
      and the adaptations and developments that have been made by laboratories, both
      academic and industrial, to enhance protein production throughput.

PMID- 15721768
TI  - DAHP synthase from Mycobacterium tuberculosis H37Rv: cloning, expression, and
      purification of functional enzyme.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading
      cause of mortality due to a bacterial pathogen. According to the 2004 Global TB
      Control Report of the World Health Organization, there are 300,000 new cases per
      year of multi-drug resistant strains (MDR-TB), defined as resistant to isoniazid
      and rifampicin, and 79% of MDR-TB cases are now "super strains," resistant to at
      least three of the four main drugs used to treat TB. Thus there is a need for the
      development of effective new agents to treat TB. The shikimate pathway is an
      attractive target for the development of antimycobacterial agents because it has
      been shown to be essential for the viability of M. tuberculosis, but absent from
      mammals. The M. tuberculosis aroG-encoded 3-deoxy-d-arabino-heptulosonate 7
      phosphate synthase (mtDAHPS) catalyzes the first committed step in this pathway.
      Here we describe the PCR amplification, cloning, and sequencing of aroG
      structural gene from M. tuberculosis H37Rv. The expression of recombinant mtDAHPS
      protein in the soluble form was obtained in Escherichia coli Rosetta-gami (DE3)
      host cells without IPTG induction. An approximately threefold purification
      protocol yielded homogeneous enzyme with a specific activity value of 0.47U mg(
      1) under the experimental conditions used. Gel filtration chromatography results
      demonstrate that recombinant mtDAHPS is a pentamer in solution. The availability
      of homogeneous mtDAHPS will allow structural and kinetics studies to be performed
      aiming at antitubercular agents development.

PMID- 15721770
TI  - Unusual stability of manganese superoxide dismutase from a new species, Tatumella
      ptyseos ct: its gene structure, expression, and enzyme properties.
AB  - A genomic DNA of 1416 bp containing an open reading frame encoding a manganese
      superoxide dismutase (Mn-SOD) from Tatumella ptyseos ct was cloned. Sequence
      analysis of this new gene revealed that it translates 205 amino acid residues.
      The deduced amino acid sequence showed variable identities (41-91%) with
      sequences of Mn-SODs from other species. The residues required to coordinate the
      single trivalent manganese ion and the 11 residues putatively involved in the
      active center are conserved as they are in other reported Mn-SODs. In addition,
      the gene was introduced into the expression vector, pET-20b(+), and transformed
      in Escherichia coli BL21(DE3). The Mn-SOD was purified by a His-tag technique.
      The yield was 0.9 mg from 0.5 L of culture. The specific activity was 6540 U/mg.
      A dimer is the major form of the enzyme in equilibrium. The half-life of dimer is
      approximately 50 min and its thermal inactivation rate constant k(d) was 0.015
      min(-1) at 80 degrees C. The dimerization of the enzyme was inhibited under an
      acidic pH (below 4.0), or in the presence of SDS (above 1%) or imidazole (above
      0.5 M), whereas it was not affected under an alkaline pH (above 9.0).
      Furthermore, the dimeric enzyme was much more resistant to proteolytic attack
      after 3 h of incubation at 37 degrees C with trypsin and chymotrypsin. This
      unusually stable enzyme can be used as cosmetic to the protection of skin against
      the unaesthetic effects caused by free radicals.

PMID- 15721769
TI  - Preparation of specifically activatable endopeptidase derivatives of Clostridium
      botulinum toxins type A, B, and C and their applications.
AB  - Clostridium botulinum neurotoxins are potently toxic proteins of 150 kDa with
      specific endopeptidase activity for SNARE proteins involved in vesicle docking
      and release. Following treatment with trypsin, a fragment of botulinum neurotoxin
      serotype A that lacks the C-terminal domain responsible for neuronal cell
      binding, but retains full catalytic activity, can be obtained. Known as the LH(N)
      fragment, we report the development of a recombinant expression and purification
      scheme for the isolation of comparable fragments of neurotoxin serotypes B and C.
      Expressed as maltose-binding protein fusions, both have specific proteolytic
      sites present between the fusion tag and the light chain to facilitate removal of
      the fusion, and between the light chain endopeptidase and the H(N) translocation
      domains to facilitate activation of the single polypeptide. We have also used
      this approach to prepare a new variant of LH(N)/A with a specific activation site
      that avoids the need to use trypsin. All three LH(N)s are enzymatically active
      and are of low toxicity. The production of specifically activatable LH(N)/A,
      LH(N)/B, and LH(N)/C extends the opportunities for exploitation of neurotoxin
      fragments. The potential utility of these fragments is discussed.

PMID- 15721771
TI  - In vitro refolding of carboxypeptidase T precursor from Thermoactinomyces
      vulgaris obtained in Escherichia coli as cytoplasmic inclusion bodies.
AB  - Carboxypeptidase T precursor from Thermoactinomyces vulgaris, which fails to
      contain its own leader peptide, has been expressed in Escherichia coli as
      insoluble cytoplasmic inclusion bodies. The yield of a washed recombinant protein
      from 1 L of culture liquid was about 60 mg. The obtained inclusion bodies were
      denatured in 6 M guanidine-HCl and then renatured by a rapid dilution. The
      important role of calcium for the complete stabilization of the refolded
      carboxypeptidase T precursor was established. After removal of minor admixture
      proteins by gel-filtration through Superdex 75, an electrophoretically
      homogeneous preparation of the native precursor of carboxypeptidase T was
      obtained. Processing of the resulting protein by subtilisin led to the formation
      of the mature carboxypeptidase T in which N-terminal sequence, molecular size,
      thermal stability, and catalytic properties were comparable to those of the
      natural enzyme.

PMID- 15721773
TI  - Direct proteolysis-based purification of an overexpressed hyperthermophile
      protein from Escherichia coli lysate: a novel exploitation of the link between
      structural stability and proteolytic resistance.
AB  - The susceptibility of a peptide bond to cleavage by a protease is determined by:
      (a) the flexibility of the protein chain region in which it is located, (b) the
      extent to which the bond is exposed, and (c) the nature of the local interactions
      made by the sidechains of its flanking residues. Each of these parameters is
      known to be influenced by the overall structural stability of the protein; thus,
      proteins of higher structurally stability commonly show higher resistance to
      proteolysis. Extrapolating this relationship to 'ultrastable' proteins, our
      intention here was to investigate whether a hyperthermophile protein expressed
      and folded within Escherichia coli could prove to be so resistant to proteolysis
      as to allow direct purification from complex mixtures of E. coli cytoplasmic
      and/or membrane proteins, through proteolytic means. Thus, we cloned the gene
      encoding the triosephosphate isomerase enzyme of Pyrococcus furiosus (PfuTIM) and
      overexpressed it in E. coli in fusion with glutathione S-transferase (GST). The
      GST-PfuTIM fusion product partitioned mainly into the insoluble fraction of the
      whole cell lysate. Upon exposure of the E. coli cell lysate precipitate fractions
      to the non-specific protease, subtilisin, all polypeptides barring PfuTIM
      (including the GST affinity tag cloned in fusion with PfuTIM) were found to be
      degraded to undetectable levels. Trace residual amounts of an E. coli protein,
      OmpF, survived proteolytic digestion, together with an extremely pure population
      of PfuTIM. Either autonomously or in combination with the more conventional
      method of heating solutions to enrich heat-stable proteins through the thermal
      unfolding and aggregation of all other proteins, such proteolysis-based
      purification could prove to be useful.

PMID- 15721772
TI  - Expression and characterization of human CB1 cannabinoid receptor in
      methylotrophic yeast Pichia pastoris.
AB  - For the purpose of purification and structural characterization, the CB1
      cannabinoid receptors are expressed in methylotrophic yeast Pichia pastoris. The
      expression plasmid was constructed in which the CB1 gene is under the control of
      the highly inducible promoter of P. pastoris alcohol oxidase I gene. To
      facilitate easy detection and purification, a FLAG tag was introduced at the N
      terminal, a c-myc epitope and a hexahistidine tag were introduced at the C
      terminal of the CB1. In membrane preparations of CB1 gene transformed yeast
      cells, Western blot analysis detected the expression of CB1 proteins. Radioligand
      binding assays demonstrated that the tagged CB1 receptors expressed in P.
      pastoris have a pharmacological profile similar to that of the untagged CB1
      receptors expressed in mammalian systems. Furthermore, the tagged CB1 receptors
      were purified by anti-FLAG M2 affinity chromatography and the identity of the
      purified CB1 receptor proteins was confirmed by Western blot analysis. MALDI/TOF
      mass spectrometry analysis of the peptides extracted from tryptic digestions of
      purified CB1 preparations detected 17 peptide fragments derived from the CB1,
      thus further confirming the identity of the purified receptor. In conclusion,
      these data demonstrated for the first time that epitope tagged, functional CB1
      cannabinoid receptors can be expressed in P. pastoris for purification and mass
      spectrometry characterization.

PMID- 15721774
TI  - Purification of recombinant proteins from mammalian cell culture using a generic
      double-affinity chromatography scheme.
AB  - Transient transfection of mammalian cells has proven to be a useful technique for
      the rapid production of recombinant proteins because of its ability to produce
      milligram quantities within 2 weeks following cloning of their corresponding
      cDNA. This rapid production also requires a fast and efficient purification
      scheme that can be applied generically, typically through the use of affinity
      tags such as the polyhistidine-tag for capture by immobilized metal-affinity
      chromatography (IMAC) or the Strep-tag II, which binds to the StrepTactin
      affinity ligand. However, one-step purification using either of these tags has
      disadvantages in terms of yield, elution conditions, and purity. Here, we show
      that the addition of both Strep-tag-II and (His)(8) to the C-terminal of r
      proteins allows efficient purification by consecutive IMAC and StrepTactin
      affinity. This approach has been successfully demonstrated using the
      intracellular protein DsRed, as well as two secreted proteins, secreted alkaline
      phosphatase (SEAP) and vascular endothelial growth factor (VEGF), all produced by
      transient transfection of HEK293-EBNA1 cells in medium supplemented with bovine
      calf serum. All proteins were purified to >99% homogeneity with yields varying
      from 29 to 81%.

PMID- 15721775
TI  - Purification of streptomycin adenylyltransferase from a recombinant Escherichia
      coli.
AB  - Bacterial resistance to aminoglycosides continues to escalate and is widely
      recognized as a serious health threat, contributing to interest in understanding
      the mechanisms of resistance. One important mechanism of streptomycin
      modification is through ATP dependent O-adenylation, catalyzed by streptomycin
      adenylyltransferase (SMATase). The aim of this study was to purify the
      recombinant SMATase by Ni(2+)-IDA-His bind resin column chromatography.
      Thioredoxin-His6-tagged SMATase fusion protein was produced in a bacterial
      intracellular expression system mainly in a soluble form. The purified fusion
      protein showed a single band on SDS-PAGE corresponding to 49 kDa. The recovery of
      fusion protein was 47% with ninefold purification. The fusion system provided a
      single step, easy and very rapid purification of SMATase and is suitable for
      obtaining a highly purified functional protein of interest. The fusion does not
      affect the functionality of the protein.

PMID- 15721776
TI  - Multidrug transporter MexB of Pseudomonas aeruginosa: overexpression,
      purification, and initial structural characterization.
AB  - Structural and functional characterization of the multidrug transporter, MexB, of
      Pseudomonas aeruginosa is significantly restricted due to a low yield of
      approximately 0.1 mg/L of culture from natural sources. To facilitate structural
      studies of this medically important transporter protein, we developed a large
      scale system for expression of the genetically engineered recombinant, MexB, in
      the Escherichia coli cell. Using the system, the eventual yield of MexB attained
      was about 10mg/L of culture. The optimized purification protocol in the presence
      of dodecyl beta-D-maltoside allowed isolation of highly homogeneous MexB. The
      oligomeric state of the protein in detergent solution has been characterized to
      verify that the native state of the purified protein has been preserved. The
      molecular mass of the protein-detergent complex was found to be 380-450kDa. The
      MexB-dodecyl beta-d-maltoside mass ratio was determined to be 1.8 +/- 0.05.
      Taking into account the monomeric MexB molecular mass deduced from its amino acid
      sequence (112.8 kDa), we concluded that the purified MexB exists as the
      homotrimer in the surfactant solution. Circular dichroism analysis of MexB showed
      dominance of the alpha-helix structures. High yield, homogeneity, and stability
      of MexB position it as a good candidate for structural and functional
      characterization.

PMID- 15721777
TI  - Expression of both Chlamydia pneumoniae RNase HIIs in Escherichia coli.
AB  - Both genes encoding the RNase HIIs from Chlamydia pneumoniae AR 39 (discriminated
      as CpRNase HIIa and CpRNase HIIb in this report) were cloned and efficiently
      expressed in Escherichia coli. These genes amplified from Chlamydial genomes with
      PCR were digested with restriction endonucleases and then cloned into plasmid pET
      28a predigested with the same enzymes. DNA sequencing confirmed that the
      constructs were correct in translation frame and coding sequence. Recombinant
      RNase HIIs were over-expressed by 0.5 mM IPTG induction. CpRNase HIIa existed
      mainly as inclusion bodies while CpRNase HIIb mainly as soluble fractions in E.
      coli. The soluble proteins were 20% of total expressed CpRNase HIIa and 65% of
      total expressed CpRNase HIIb, respectively. Native purification and denaturing Ni
      NTA purification were performed to recover the recombinant CpRNase HIIs from
      induced bacteria. 3.36 mg CpRNase HIIa and 18 mg CpRNase HIIb were, respectively,
      obtained from 1 g wet bacteria with native Ni-NTA purification. Denaturing Ni-NTA
      purification recovered 14.48 mg CpRNase HIIa and 10.4 mg CpRNase HIIb from 1 g
      wet bacteria, respectively. Although the proteins recovered by denaturing Ni-NTA
      purification were inactive, re-folding by dialysis against decreased
      concentrations of urea could generate CpRNase HIIa and CpRNase HIIb as active as
      those recovered by native Ni-NTA purification. These efforts offered basis for
      further study on the structure-function relationships and their biological
      importance of Chlamydial RNase HIIs.

PMID- 15721778
TI  - Two methods for large-scale purification of recombinant human choline
      acetyltransferase.
AB  - Choline acetyltransferase (ChAT) catalyzes the transfer of an acetyl group from
      acetyl-CoA to choline to produce the neurotransmitter acetylcholine (ACh). We
      have produced large quantities of pure human ChAT using two different bacterial
      expression systems. In the first, ChAT is fused to a chitin-binding domain via a
      self-cleavable linker allowing the release of ChAT without the use of proteases.
      In the second, ChAT is fused to a hexahistidine (His6) tag at the N-terminus with
      a linker incorporating a TEV protease cleavage site. In both cases, pure ChAT was
      produced that has a final specific activity of approximately 50 micromol
      ACh/min/mg and is suitable for structural characterization. Analysis of purified
      ChAT by Western blots and mass spectrometry revealed that the C-terminal 15 amino
      acids were slowly removed by endogenous proteolytic activity, to produce a stable
      615 residue protein. Furthermore, we show that purified recombinant human ChAT is
      highly prone to oxidation, leading to the formation of covalent dimers and/or a
      loss of catalytic activity. Kinetic parameters of our purified proteins were
      obtained and, when compared to previously published constants for human placental
      ChAT, we found that recombinant human ChAT displays lower values for Michaelis
      and inhibition constants for ACh, which may be due to the complete absence of
      post-translational modifications.

PMID- 15721779
TI  - Rapid, high-yield expression and purification of Ca2+-ATPase regulatory proteins
      for high-resolution structural studies.
AB  - Phospholamban (PLB) and sarcolipin (SLN) are small integral membrane proteins
      that regulate the Ca(2+)-ATPases of cardiac and skeletal muscle, respectively,
      and directly alter their calcium transport properties. PLB interacts with and
      regulates the cardiac Ca(2+)-ATPase at submaximal calcium concentrations, thereby
      slowing relaxation rates and reducing contractility in the heart. SLN interacts
      with and regulates the skeletal muscle Ca(2+)-ATPase in a mechanism analogous to
      that used by PLB. While these regulatory interactions are biochemically and
      physiologically well characterized, structural details are lacking. To pursue
      structural studies, such as electron cryo-microscopy and X-ray crystallography,
      large quantities of over-expressed and purified protein are required. Herein, we
      report a modified method for producing large quantities of PLB and SLN in a rapid
      and efficient manner. Briefly, recombinant wild-type PLB and SLN were over
      produced in Escherichia coli as maltose binding protein fusion proteins. A
      tobacco etch virus protease site allowed specific cleavage of the fusion protein
      and release of recombinant PLB or SLN. Selective solubilization with guanidine
      hydrochloride followed by reverse-phase HPLC permitted the rapid, large-scale
      production of highly pure protein. Reconstitution and measurement of ATPase
      activity confirmed the functional interaction between our recombinant regulatory
      proteins and Ca(2+)-ATPase. The inhibitory properties of the over-produced
      proteins were consistent with previous studies, where the inhibition was relieved
      by elevated calcium concentrations. In addition, we show that our recombinant PLB
      and SLN are suitable for high-resolution structural studies.

PMID- 15721780
TI  - Overexpression, refolding, and purification of the major immunodominant outer
      membrane porin OmpC from Salmonella typhi: characterization of refolded OmpC.
AB  - The major immunodominant integral outer membrane protein C (OmpC) from Salmonella
      typhi Ty21a was overexpressed, without the signal peptide, in Escherichia coli.
      The protein aggregates as inclusion bodies (IBs) in the cytoplasm. OmpC from IBs
      was solubilized with 4 M urea and refolded. This involved rapid dilution of
      unfolded OmpC into a refolding buffer containing polyoxyethylene-9-lauryl ether
      (C(12)E(9)) and glycerol. The refolded OmpC (rfOmpC) was shown to be structurally
      similar to the native OmpC by SDS-PAGE, Western blotting, tryptic digestion,
      ultrafiltration, circular dichroism, and fluorescence spectroscopic techniques.
      Crystals of rfOmpC were obtained in preliminary crystallization trials. The
      rfOmpC also sets a stage for rational design by recombinant DNA technology for
      vaccine design and high resolution structure determination.

PMID- 15721781
TI  - Cloning, expression, and purification of Brucella suis outer membrane proteins.
AB  - Brucella, an aerobic, nonsporeforming, nonmotile Gram-negative coccobacillus, is
      a NIH/CDC category B bioterror threat agent that causes incapacitating human
      illness. Medical defense against the bioterror threat posed by Brucella would be
      strengthened by development of a human vaccine and improved diagnostic tests.
      Central to advancement of these goals is discovery of bacterial constituents that
      are immunogenic or antigenic for humans. Outer membrane proteins (OMPs) are
      particularly attractive for this purpose. In this study, we cloned, expressed,
      and purified seven predicted OMPs of Brucella suis. The recombinant proteins were
      fused with 6-His and V5 epitope tags at their C termini to facilitate detection
      and purification. The B. suis surface genes were PCR synthesized based on their
      ORF sequences and directly cloned into an entry vector. The recombinant entry
      constructs were propagated in TOP 10 cells, recombined into a destination vector,
      pET-DEST42, then transformed into Escherichia coli BL21 cells for IPTG-induced
      protein expression. The expressed recombinant proteins were confirmed with
      Western blot analysis using anti-6-His antibody conjugated with alkaline
      phosphatase. These B. suis OMPs were captured and purified using a HisGrab plate.
      The purified recombinant proteins were examined for their binding activity with
      antiserum. Serum derived from a rabbit immunized intramuscularly with dialyzed
      cell lysate of Brucella rough mutant WRR51. The OMPs were screened using the
      rabbit antiserum and purified IgG. The results suggested that recombinant B. suis
      OMPs were successfully cloned, expressed and purified. Some of the expressed OMPs
      showed high binding activity with immunized rabbit antiserum.

PMID- 15721782
TI  - Bacterial expression and enzymatic activity analysis of ME1, a ribosome
      inactivating protein from Mirabilis expansa.
AB  - Ribosome-inactivating proteins (RIPs) are toxic proteins synthesized by many
      plants and some bacteria, that specifically depurinate the 28S RNA and thus
      interrupt protein translation. RIPs hold broad interest because of their
      potential use as plant defense factors against pathogens. However, study of the
      activity of type I RIPs has been hampered since their expression in Escherichia
      coli has typically been toxic to the model system. Mirabilis expansa, an Andean
      root crop, produces a type I RIP called ME1 in large quantities in its storage
      roots. In this study, the cDNA sequence of ME1 was used to successfully express
      the recombinant ME1 protein in E. coli. The production of recombinant ME1 in E.
      coli was confirmed by Western blot analysis using anti-ME1 antibodies. The
      studies with fluorescence-labeled ME1 showed that ME1 can enter bacteria and be
      distributed in the cytoplasm uniformly, indicating its ability to access the
      protein synthesis machinery of the bacteria. The recombinant enzyme was active
      and depurinated yeast ribosomes. However, both native and recombinant ME1
      proteins failed to depurinate the E. coli ribosomes, explaining the non-toxicity
      of recombinant ME1 to E. coli. Structural modeling of ME1 showed that it has
      folding patterns similar to other RIPs, indicating that ME1 and PAP, which share
      a similar folding pattern, can show different substrate specificity towards E.
      coli ribosomes. The results presented here are very significant, as few reports
      are available in the area of bacterial interaction with type I RIPs.

PMID- 15721783
TI  - Yersinia pestis outer membrane type III secretion protein YscC: expression,
      purification, characterization, and induction of specific antiserum.
AB  - The type III secretion system (YscC) protein of Yersinia pestis plays an
      essential role in the translocation of Yersinia outer proteins (Yops) into
      eukaryotic target cells through a type III secretion mechanism. To assess the
      immunogenicity and potential protective efficacy of YscC against lethal plague
      challenge, we cloned, overexpressed, and purified YscC using two different
      bacterial expression and purification systems. The resulting expression plasmids
      for YscC, pETBlue-2-YscC and pTYB11-YscC, were regulated by robust T7 promoters
      that were induced with isopropyl-beta-D-thiogalactopyranoside. The intein-fusion
      pTYB11-YscC system and the six-histidine-tagging pETBlue-2-YscC system were both
      successful for producing and purifying YscC. The intein-mediated purification
      system produced about 1mg of soluble YscC per liter of bacterial culture while
      the YscC-His(6)-tag method resulted in 16mg of insoluble YscC per liter of
      bacterial culture. Protein identity for purified YscC-His(6) was confirmed by ion
      trap mass spectrometry. Antisera were produced against both YscC and YscC-His(6).
      The specific immune response generated in YscC-vaccinated mice was relative to
      the particular purified protein, YscC or YscC-His(6), which was used for
      vaccination as determined by Western blot analysis and ELISA. Regardless of the
      purification method, either form of the YscC protein failed to elicit a
      protective immune response against lethal plague challenge with either F1 capsule
      forming Y. pestis CO92 or the isogenic F1(-)Y. pestis C12.

PMID- 15721784
TI  - Efficient production of Clostridium botulinum exotoxin C3 in bacteria: a
      screening method to optimize production yields.
AB  - Clostridium botulinum exoenzyme C3 is responsible for the inactivation of members
      of the Rho GTPase family that are implicated in actin-cytoskeleton
      reorganization. This property has been extensively used in the field to
      investigate the functionality of the Rho GTPases. However, systematic analysis of
      Rho GTPase functions requires large amounts of such inhibitors and consequently
      an optimization of the production yield of these proteins. Bacterial production
      of soluble proteins often requires a refolding step that noticeably affects the
      production yields and necessitates additional experiments to verify functional
      activity. This is particularly true for TAT-C3, the production yields of which
      are generally low. In this report, we describe a rapid and efficient method for
      the production of soluble C3 exoenzyme developed by screening a collection of
      bacterial strains. The recombinant C3 protein was fused to the TAT protein
      transduction domain from HIV, to allow protein delivery into cells, and to a
      hexahistidine tag, that permitted purification by Nickel affinity chromatography.
      We have demonstrated the production of large amounts of soluble and functional
      protein using the bacterial strain AD494 (DE3)pLysS. This rapid and efficient
      method for the production of soluble C3 exoenzyme could also be useful for the
      production of other proteins with solubility problems.

PMID- 15721785
TI  - Expression and purification of recombinant 38-kDa and Mtb81 antigens of
      Mycobacterium tuberculosis for application in serodiagnosis.
AB  - Availability of genome sequence of Mycobacterium tuberculosis has accelerated
      identification of antigens for serodiagnosis of tuberculosis and a number of new
      antigens are being tested in various combinations to produce cocktails with high
      sensitivity and specificity. For producing a highly specific diagnostic test, it
      is important that the recombinant antigens be highly pure, free of host protein,
      and correctly folded so that they bind only to specific antibodies. Also, for
      commercial viability they need to be produced in high yields. We have cloned,
      expressed, and purified a number of mycobacterial antigens in Escherichia coli.
      This paper describes, expression and purification of two important mycobacterial
      proteins with serodiagnostic potential, namely, 38-kDa and Mtb81 antigens, in
      monomeric form. The protocol involves using a T7 promoter based expression vector
      under conditions of regulated and slow expression followed by three-step column
      chromatography procedure to obtain highly purified proteins. The yields of the
      two proteins were several folds higher than previously reported. The purified
      proteins were useful in detecting antibodies in sera of tuberculosis patients
      (smear positive, smear negative, and extra-pulmonary categories).

PMID- 15721786
TI  - Identification and purification of a soluble region in the breast cancer
      susceptibility protein BRCA2.
AB  - The BRCA2 gene encodes a large multidomain protein of 3418 residues. Studies to
      elucidate the mechanisms by which BRCA2 prevents tumour formation have been
      largely restricted by the size of the protein. Based on secondary structure
      predictions we have cloned regions across the BRCA2 gene and determined the
      solubility of the proteins they encode. The fragment consisting of amino acids
      290-456 BRCA2 was found predominantly in the soluble portion of the cell lysate
      and was purified by ion exchange and nickel-NTA affinity chromatography. CD
      spectroscopy revealed secondary structure elements consistent with a folded
      peptide and limited proteolysis was used to identify a potential novel domain.

PMID- 15721787
TI  - Production of recombinant amyloid-beta peptide 42 as an ubiquitin extension.
AB  - Amyloid-beta peptide 42 (Abeta42) mediates neuronal degeneration in Alzheimer's
      disease (AD). We sought to produce recombinant Abeta42 as an ubiquitin extension.
      A synthetic oligonucleotide encoding Abeta42 was constructed and cloned as an
      extended polypeptide of hexahistidine-tagged ubiquitin (H(6)Ub) using the pET
      vector. Isopropyl-beta-D-thiogalactopyranoside induction of transformed
      Escherichia coli resulted in the production of large amounts of insoluble H(6)Ub
      Abeta42 fusion protein. H(6)Ub-Abeta42 was solubilized in 8 M urea and applied to
      a nickel-nitrilotriacetic acid affinity column for purification. Column washing
      removed the urea and soluble H(6)Ub-Abeta42 was eluted, indicating that
      covalently attached ubiquitin prevented Abeta42 from aggregating. Abeta42 was
      cleaved from H(6)Ub using recombinant yeast ubiquitin hydrolase-1 (YUH-1) and
      purified using reverse-phase chromatography. The recombinant Abeta42 prepared in
      this study has the same toxic effect on human neuroblastoma SH-SY5Y cells
      comparing with chemically synthesized, commercial one. The peptide yield was more
      than 4 mg/L culture, indicating this ubiquitin fusion technique is an attractive
      method for production of aggregation-prone peptides such as Abeta42.

PMID- 15721788
TI  - Expression and purification of a recombinant enantioselective amidase.
AB  - Microbacterium sp. AJ115 metabolises a wide range of nitriles using the two-step
      nitrile hydratase/amidase pathway. In this study, the amidase gene of
      Microbacterium sp. AJ115 has been inserted into the pCal-n-EK expression vector
      and expressed in Escherichia coli BL21(DE3)pLysS. The expressed protein is active
      in E. coli and expression of the amidase gene allows E. coli to grow on acetamide
      as sole carbon and/or nitrogen source. Expression of active amidase in E. coli
      was temperature dependent with high activity found when cultures were grown
      between 20 and 30 degrees C but no activity at 37 degrees C. On induction, the
      amidase represents 28% of the total soluble protein in E. coli. The expressed
      amidase has been purified in a single step from the crude lysate using the
      calmodulin-binding peptide (CBP) affinity tag. The V(max) and K(m) of the
      purified enzyme with acetamide (50 mM) were 4.4 micromol/min/mg protein and
      4.5mM, respectively. The temperature optimum was found to be 50 degrees C.
      Purified enzyme demonstrated enantioselectivity with the ability to
      preferentially act on the S enantiomer of racemic (R,S)-2-phenylpropionamide. S-2
      phenylpropionic acid is produced with an enantiomeric excess of >82% at 50%
      conversion of the parent amide.

PMID- 15721789
TI  - Overexpression, purification, and characterization of PDZ domain proteins NHERF
      and E3KARP in Escherichia coli.
AB  - NHERF (Na(+)/H(+) exchanger regulatory factor) and E3KARP (NHE3 kinase A
      regulatory protein or NHERF2) are structurally related adapter proteins that
      contain two tandem PDZ (PSD-95/Dlg-1/ZO-1) domains. Recent studies suggest that
      these proteins play important roles in the membrane targeting, trafficking, and
      sorting of several ion channels, transmembrane receptors, and signaling proteins
      in many tissues. Both NHERF and E3KARP interact with NHE3 through their C
      terminally extended second PDZ domain, and the last 30 amino acids of these PDZ
      domain proteins interact with ezrin. However, the structural bases of the full
      length human NHERF and E3KARP, in their physiological roles on the regulation of
      NHE3 trafficking, are still unknown. To obtain pure and soluble proteins for
      crystallization and X-ray studies, NHERF and E3KARP were subcloned into pET-30b
      and pET-30a vectors, and overexpressed in Escherichia coli strains of BL21(DE3).
      The soluble NHERF and E3KARP proteins were purified using Ni-NTA, anion-exchange
      column and gel filtration chromatography. The purity, molecular mass, and the
      conformation of the proteins were determined by high-performance liquid
      chromatography, matrix-assisted laser desorption-ionization-time-of-flight mass
      spectroscopy and circular dichroism studies, respectively.

PMID- 15721790
TI  - Discovery of a novel N-iminylamidase activity: substrate specificity,
      chemicoselectivity and catalytic mechanism.
AB  - Enzymatic hydrolysis of the N-iminylamide was investigated in this study. An
      enzyme possessing N-iminylamidase activity from pig liver was purified to
      electrophoretic homogeneity. This enzyme was also active, however, with imides
      and appears to be identical to pig liver imidase. The identification was
      confirmed by copurification of enzyme activities and by specificities of typical
      substrates of mammalian imidase, such as phthalimide, dihydrouracil, and
      maleimide. The hydrolysis of 3-iminoisoindolinone was further analyzed by HPLC,
      (13)C NMR spectrometry, and LC-MS measurements to determine its
      chemicoselectivity. All data indicated that this enzyme chemicoselectively
      catalyzed the hydrolysis of the N-iminylamide to produce the compound bearing the
      diamine and carboxylate group. The pH profiles of this enzyme suggest that one of
      the protons of 3-iminoisoindolinone was important to promote the ring-opening
      process of this substrate. These results constituted a first study on the
      enzymatic hydrolysis of compounds bearing the N-iminylamide functional group.

PMID- 15721791
TI  - High-level expression of a novel amine-synthesizing enzyme, N-substituted
      formamide deformylase, in Streptomyces with a strong protein expression system.
AB  - N-substituted formamide deformylase (NfdA) from Arthrobacter pascens F164 is a
      novel deformylase involved in the metabolism of isonitriles. The enzyme catalyzes
      the deformylation of an N-substituted formamide, which is produced from the
      corresponding isonitrile, to yield the corresponding amine and formate. The nfdA
      gene from A. pascens F164 was cloned into different types of expression vectors
      for Escherichia coli and Streptomyces strains. Expression in E. coli resulted in
      the accumulation of an insoluble protein. However, Streptomyces strains
      transformed with a P(nitA)-NitR system, which we very recently developed as a
      regulatory gene expression system for streptomycetes, allowed the heterologous
      overproduction of NfdA in an active form. When Streptomyces lividans TK24
      transformed with pSH19-nfdA was cultured under the optimum conditions, the NfdA
      activity of the cell-free extract amounted to 8.5 U/mg, which was 29-fold higher
      than that of A. pascens F164. The enzyme also comprised approximately 20% of the
      total extractable cellular protein. The recombinant enzyme was purified to
      homogeneity and characterized. The expression system established here will allow
      structural analysis and mutagenesis studies of NfdA.

PMID- 15721792
TI  - Stimulant-induced adaptations in neostriatal matrix and striosome systems:
      transiting from instrumental responding to habitual behavior in drug addiction.
AB  - Converging evidence indicates that repeated exposure to motor stimulants such as
      cocaine and amphetamine produces marked alterations in network responsiveness of
      striatal neurons to subsequent challenge with the same stimulant drug. Such
      alterations, which correlate with persistent patterns of repetitive behavior,
      associate with distinct compartmental changes in the neostriatum. Striatal matrix
      system neurons undergo "silencing" following repeated drug challenges, allowing
      striosome system neurons to exhibit preferential activation. Matrix neurons are
      innervated by sensory and motor areas of neocortex and are activated in the
      course of on-going, adaptive behavior. Inactivation of matrix neurons by chronic
      stimulant exposure may therefore constrain sensorimotor and cognitive processing.
      In turn, the striosomes are anatomically connected through re-entrant loops with
      limbic prefrontal and allocortical structures, such as anterior cingulate cortex,
      orbital frontal cortex, and basolateral amygdala, all of which play a part in
      stimulant-induced reinforcement and relapse to drug-taking. Moreover, functional
      evidence links striosome system neurons, which are responsible for providing
      inhibitory regulatory feedback to midbrain dopamine neurons, with reinforcement
      based processes. In considering such evidence, we postulate that recurrent matrix
      inactivation and recruitment of striosome-based pathways by chronic stimulant
      exposure represent neural end-points of the transit from action-outcome
      associative behavior to conditioned habitual responding. Within this theoretical
      framework, habitual behavior can be elicited by both interoceptive cues and
      exteroceptive conditioned stimuli to promote the automatic execution of learned
      responses.

PMID- 15721793
TI  - The effects of the dopamine D1 receptor antagonist SCH23390 on memory
      reconsolidation following reminder-activated retrieval in day-old chicks.
AB  - This series of experiments examined the involvement of the dopamine D1 receptor
      antagonist, SCH23390, on memory reconsolidation following reminder-activated
      retrieval. Day-old male New HampshirexWhite Leghorn chicks were trained on a
      single trial passive avoidance task. A dose of 0.5 mg/kg of SCH23390 was
      administered subcutaneously 5 min before reminder trials, which were presented at
      30, 60, and 90 min following training. Memory deficits were observed when
      reminder trials were presented at 30 and 60 min following training, but not when
      a reminder was presented at 90 min. No effect on memory retention was observed
      when reminder trials were not presented, suggesting that reconsolidation
      mechanisms were both contingent on the presentation of the reminder and
      independent of the consolidation process. Following a reminder presented at 60
      min post-training, deficits in memory retention emerged between 45 and 60 min.
      The deficit was prolonged, lasting for up until 48 h after reminder presentation.
      The results indicate an important role for the D1 receptor in reconsolidation
      processes.

PMID- 15721794
TI  - Modulation of working, short- and long-term memory by nicotinic receptors in the
      basolateral amygdala in rats.
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, mecamylamine
      (1.0 or 10.0 microg/side), or nicotine (0.6 or 3.0 microg/side) 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)
      5 s after training, then for short-term memory (STM) 90 min later, and finally
      for long-term memory (LTM) 24 h later. Mecamylamine depressed and nicotine
      enhanced WM, STM, and LTM. In Experiment 2, the treatments were given after WM
      was presumably over. Again, mecamylamine inhibited and nicotine enhanced STM and
      LTM. The results indicate that nAChRs in BLA participate in the regulation of WM
      formation and STM and LTM acquisition and consolidation.

PMID- 15721795
TI  - Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the
      inhibitory avoidance, but not in the open field habituation task, in rats.
AB  - CB1 is the most abundant metabotropic receptor of the brain, being found in areas
      classically involved in learning and memory and present at higher density at
      presynaptic terminals. Different sets of evidence support the idea that
      endogenous ligands (endocannabinoids) to the CB1 receptors act as modulators of
      neurotransmission. In hippocampus, endocannabinoids seem to act as retrograde
      messengers mediating down-regulation of GABA release. Previous reports have
      described a cognitive impairment effect of cannabinoid agonists, or facilitation
      by antagonists. The scope of the present study is to investigate the effect of
      intrahippocampal administration of the CB1-selective antagonist, AM251, in two
      behavioral tasks. One hundred and twelve male Wistar rats with bilateral cannulae
      implanted in the CA1 region of the dorsal hippocampus were trained in a step-down
      inhibitory avoidance task (IA, footshock, 0.5 mA) or an open field habituation
      task (OF). Immediately, after training, animals received an infusion of 0.55,
      5.5, and 55.5 ng/side of AM251 (Tocris), or its vehicle (DMSO/saline), via these
      cannulae. Our results show that AM251 disrupted memory consolidation of the IA
      task, but not the OF task, an effect that seems to be purely mnemonic since the
      drug showed no motor performance effects. Only the intermediate dose (5.5
      ng/side) of AM251 was effective in IA and the absence of effect with the larger
      dose may be the consequence of non-specific binding. The fact that OF was not
      affected raises the possibility that this endogenous system requires some degree
      of aversiveness to be recruited. We propose that increased levels of endogenous
      cannabinoids in the hippocampus, following a training session, contribute to
      facilitate memory consolidation, a process that may have been disrupted with
      AM251.

PMID- 15721796
TI  - The involvement of the orbitofrontal cortex in learning under changing task
      contingencies.
AB  - Previous investigations examining the rat prefrontal cortex subregions in
      attentional-set shifting have commonly employed two-choice discriminations. To
      better understand how varying levels of difficulty influence the contribution of
      the prefrontal cortex to learning, the present studies examined the effects of
      orbitofrontal cortex inactivation in a two- or four-choice odor reversal learning
      test. Long-Evans rats were trained to dig in cups that contained distinct odors.
      In the two-choice odor discrimination, one odor cup was always associated with a
      cereal reinforcement in acquisition while the opposite odor cup was associated
      with a cereal reinforcement in reversal learning. In the four-choice odor
      discrimination, an additional two cups containing distinct odors were used that
      were never associated with reinforcement in acquisition or reversal learning.
      Bilateral infusions of the GABA-A agonist, muscimol (0.5 microg) into the
      orbitofrontal cortex did not impair acquisition of either the two- or four-choice
      discrimination task. However, muscimol infusions into the orbitofrontal cortex
      impaired two- and four-choice reversal learning. In the two-choice odor reversal,
      muscimol treatment selectively increased perseverative errors. In the four-choice
      odor reversal, muscimol treatment increased perseverative, regressive, as well as
      irrelevant errors. These findings suggest that the orbital prefrontal cortex not
      only enables task switching by supporting the initial inhibition of a previously
      relevant choice pattern, but under increasing task demands also enables the
      reliable execution of a new choice pattern and reduction of interference to
      irrelevant stimuli.

PMID- 15721797
TI  - Whisker-based discrimination of object orientation determined with a rapid
      training paradigm.
AB  - Rats use their large facial whiskers to discriminate the spatial features of
      objects. Despite numerous electrophysiological recording studies in the central
      trigeminal whisker representations that document neurons tuned to the direction
      of whisker deflection, there is no behavioral evidence to date that rats can use
      their whiskers to discriminate between object orientations. In the present study,
      we characterized whisker-dependent orientation discrimination using a one-trial
      learning procedure. Sprague-Dawley rats were trained and tested in a three-arm 'Y
      maze' that was outfitted with 180 independently moveable bars that protruded into
      the arms of the maze to contact the whiskers. On the first day, the maze was
      configured to have two arms with only horizontal bars and a third arm with only
      vertical bars and rats were allowed to freely explore all arms. On the second
      day, rats were isolated in one arm that contained only vertical bars as a
      conditioned stimulus (CS) and administered three mild foot shocks. On the third
      day, the maze was configured identically to the first day and rats were once
      again allowed to freely explore the maze. We measured the percentage of time
      spent in each arm of the maze and found that most rats spent significantly less
      time in the arm containing the CS after training compared to before training.
      Subsequent control experiments determined that the conditioned avoidance was
      attributable to orientation cues, was caused by the association of the
      conditioned and unconditioned stimulus and was whisker-dependent. Avoidance
      behavior was significantly reduced when the difference between the conditioned
      and non-conditioned orientation difference was reduced to 45 degrees. Thus, rats
      can discriminate object orientation with their whiskers and an estimate of their
      discrimination thresholds can be rapidly acquired through the application of a
      one-trial learning paradigm.

PMID- 15721798
TI  - Dissociation between extension of the sensitive period for avian vocal learning
      and dendritic spine loss in the song nucleus lMAN.
AB  - Several instances of early learning coincide with significant rearrangements of
      neural connections in regions contributing to these behaviors. In fact
      developmentally restricted learning may be constrained temporally by the
      opportunity for experience to selectively maintain appropriate synapses amidst
      the elimination of exuberant connections. Consistent with this notion, during the
      normal sensitive period for vocal learning in zebra finches (Taenopygia guttata),
      there is a decline in the density of dendritic spines within a region essential
      for song development, the lateral magnocellular nucleus of the anterior
      nidopallium (lMAN). Moreover, in birds isolated from conspecific song shortly
      after hatching, both the closure of the sensitive period for vocal learning and
      the pruning of spines from lMAN neurons is delayed. Here, we employed a more
      subtle form of deprivation to delay the close of the sensitive period for song
      learning, and found that late song learning occurred without obvious alterations
      in the pruning of dendritic spines on lMAN neurons. At posthatch day (PHD) 65
      (beyond the end of the normal sensitive period for song memorization in zebra
      finches), birds isolated from song beginning on PHD30 did not differ from
      normally reared birds in measures of dendritic spine density on Golgi-Cox stained
      lMAN neurons. Moreover, tutor exposure from PHD65 to 90 did not increase spine
      elimination in these isolates (who memorized new song material) relative to
      controls (who did not). Thus, we conclude that the extent of normally occurring
      lMAN spine loss is not sufficient to account for the timing of the sensitive
      period for zebra finch song learning.

PMID- 15721799
TI  - Influence of mRNA and protein synthesis inhibitors on the long-term memory
      acquisition of classically conditioned earthworms.
AB  - We investigated the process of memory consolidation following classical
      conditioning of earthworms. Earthworms were conditioned in paired trials by a
      weak vibration as a conditioned stimulus (CS), and by light as an unconditioned
      stimulus (US). The occurrence of a shrinking response upon exposure to the CS
      increased steadily with the number of paired training trials. When the training
      procedure was changed by increasing the intertrial interval (ITI), it was found
      that only those worms trained with a 68 s ITI exhibited long-term memory
      retention for at least 24 h. The influence of mRNA synthesis inhibition by
      actinomycin-D or of protein synthesis by anisomycin on memory consolidation was
      also examined. Induction of the long-term memory was blocked when either of these
      two compounds was injected into the body cavity of the worm within 25 min of
      conditioning with the 68 s ITI. These results demonstrate that the long-term
      memory is dependent upon protein synthesis in response to the upregulation of new
      transcription messengers.

PMID- 15721800
TI  - Effects of oral cortisol treatment in healthy young women on memory retrieval of
      negative and neutral words.
AB  - Studies in rodents have demonstrated that glucocorticoids enhance memory
      consolidation but impair delayed memory retrieval. Similar findings have been
      reported in humans. Emotional items are better remembered than neutral items.
      However, it is unknown if emotional valence influences the effects of cortisol on
      retrieval. In this double-blind crossover study, 16 healthy women learned a
      wordlist containing 15 neutral and 15 negative words. Delayed recall was tested
      5h later. Cortisol administered before recall testing significantly reduced
      retrieval (p<.01). Exploratory follow-up analysis revealed that cortisol
      significantly impaired retrieval of negative words (p<.01), while having no
      significant effect on neutral words (p=.47). The current findings could suggest
      that emotional material is especially sensitive to the memory modulating effects
      of stress hormones.

PMID- 15721801
TI  - A scavenger of peroxynitrite prevents long-term memory formation using a single
      trial passive avoidance task for the day-old chick.
AB  - The important role of nitric oxide (NO) in memory processing has been recognised
      for some time. However, the mechanisms through which NO may act are only
      partially understood. One highly reactive radical brought about by the reaction
      of NO and superoxide ions is peroxynitrite. The current study investigated the
      effect of peroxynitrite scavenging on retention for a single trial passive
      avoidance task developed for the day-old chick. Administration of a range of
      concentrations of the peroxynitrite scavenger Trolox (0.1 microM-1.2 mM) yielded
      a bimodal retention curve. This dose-response curve had nadirs at 300 and 800
      microM. A time of administration study was conducted for each optimal
      concentration of Trolox and in both studies, the effective range of
      administration times extended from at least 10 min before training to 20 min post
      training. Finally, a retention function was conducted for each optimum
      concentration of Trolox and in both studies a persistent retention loss was
      observed from 40 min post-training until the conclusion of the experiment 24 h
      post-training. The findings suggest that physiological levels of peroxynitrite
      may be required for the consolidation of long-term memory in this model of memory
      formation. Interestingly, the effective times of administration and time of
      retention loss onset are consistent with previous studies which blocked NO
      synthesis. Therefore it may be suggested that NO acts to facilitate long-term
      memory formation through the production of peroxynitrite.

PMID- 15721802
TI  - The enhancing effects of hippocampal infusions of glucose are not restricted to
      spatial working memory.
AB  - Extensive evidence shows that hippocampal infusions of glucose enhance
      spontaneous alternation (SA) performance or reverse deficits in this task. The
      current experiments determined whether the enhancing effects of hippocampal
      infusions of glucose are restricted to spatial working memory. Specifically we
      tested whether hippocampal infusions of glucose would reverse deficits in an
      emotional reference memory task (continuous multiple trial inhibitory avoidance
      [CMIA]) produced by septal infusions of the gamma-aminobutyric acid agonist
      muscimol. Male Sprague-Dawley rats were given septal infusions of vehicle or
      muscimol (0.15 nmol: SA; 5 nmol: CMIA) combined with hippocampal infusions of
      vehicle or glucose (50 nmol) 15 min prior to assessing SA or CMIA training. CMIA
      retention was tested 48 h later. Muscimol infusions decreased percent alternation
      scores and avoidance retention latencies. Importantly, hippocampal infusions of
      glucose reversed the deficits produced by the septal muscimol infusions on both
      tasks. These findings show for the first time that hippocampal glucose infusions
      also influence emotional memory, indicating that the enhancing effects of glucose
      generalize to memory tasks that vary in motivational and cognitive demand.

PMID- 15721803
TI  - Retrieval improvement is induced by water shortage through angiotensin II.
AB  - Angiotensin II (ANGII) has an evolutionary preserved role in determining
      adaptative responses to water-shortages. In addition, it has been shown to
      modulate diverse phases of memory. Still, it is not clear whether ANGII improves
      or spoils memory. We demonstrated that endogenous angiotensins enhance
      consolidation of a long-term associative memory in the crab Chasmagnathus and
      that water shortage improves memory consolidation through brain ANGII actions.
      Here, we show that weakly trained crabs, when water-deprived, exhibit enhanced
      retrieval. Subsequently, memory retention is indistinguishable from that of
      strongly trained crabs. ANGII, but not angiotensin IV, is a necessary and
      sufficient condition for such enhancing effect. We conclude that ANGII released
      due to water shortage leads to enhanced memory retrieval. Thus, it seems that
      ANGII has an evolutionary preserved role as a multifunction coordinator that
      enables an adaptative response to water-shortage. The facilitation of memory
      consolidation and retrieval would be among those coordinated functions.

PMID- 15721805
TI  - Selection of quiescent Escherichia coli with high metabolic activity.
AB  - Sustained metabolic activity in non-growing, quiescent cells can increase the
      operational life-span of bio-processes and improve process economics by
      decoupling production from cell growth. Because of the ill-defined molecular
      nature of this phenotype, we developed selection protocols for the evolution of
      quiescent Escherichia coli mutants that exhibit high metabolic activity in
      ammonium starvation-induced stationary phase. The best enrichment procedures were
      continuously or discontinuously fed ammonium-limited chemostat cultures with a
      very low dilution rate of 0.03 h(-1). After 40 generations of selection, improved
      mutants with up to doubled catabolic rates in stationary phase were isolated. The
      metabolically most active clones were identified by screening for high specific
      glucose uptake rates during ammonium starvation-induced stationary phase in deep
      well microtiter plates.

PMID- 15721806
TI  - Directed evolution of copy number of a broad host range plasmid for metabolic
      engineering.
AB  - Random mutagenesis and directed evolution has been successfully used to improve
      desired properties of enzymes for biocatalysis and metabolic engineering. Here we
      employ the method to increase copy number of a pBBR-based broad host range
      plasmid, which can be used to express desired enzymes in a variety of microbial
      hosts. Localized random mutagenesis was performed in the replication control
      region of a pBBR-derived plasmid containing a beta-carotene reporter. Mutant
      plasmids were isolated that showed increased beta-carotene production. Real-time
      PCR analysis confirmed that the copy number of the mutant plasmids increased 3-7
      fold. Sequence of the 10 mutant plasmids indicated that each plasmid contained
      single or multiple mutations in the rep gene or the flanking regions. Single
      amino acid change of serine to leucine at codon 100 of the replication protein
      and single nucleotide change of C to T at 46 bp upstream of the rep gene caused
      the increase of plasmid copy number. The utility of the mutant plasmids for
      metabolic engineering were further demonstrated by increased beta-carotene
      production, when an isoprenoid pathway gene (dxs) was co-expressed on a
      compatible plasmid. The mutant plasmids were tested in Agrobacterium tumefaciens.
      Increase of plasmid copy number and beta-carotene production was also observed in
      the non-Escherichia coli host.

PMID- 15721807
TI  - Directed evolution of Escherichia coli farnesyl diphosphate synthase (IspA)
      reveals novel structural determinants of chain length specificity.
AB  - Directed evolution of farnesyl diphosphate (FPP, C15) synthase (IspA) of
      Escherichia coli was carried out by error-prone PCR with a color complementation
      screen utilizing C40 carotenoid pathway enzymes. This allowed IspA mutants with
      enhanced production of the C40 carotenoid precursor geranylgeranyl diphosphate
      (GGPP, C20) to be readily identified. Analysis of these mutants was carried out
      in order to better understand the mechanisms of product chain length specificity
      in this enzyme. The 12 evolved clones having enhanced C20 GGPP production have
      characteristic mutations in the conserved regions of prenyl diphosphate synthases
      (designated regions I through VII). Some of these mutations (I76T, Y79S, Y79H,
      C75Y, H83Y, and H83Q) are found near or before the conserved first aspartate rich
      motif (FARM), which is involved in the mechanism for chain elongation reaction of
      all prenyl synthases. Molecular modeling suggested a mechanism for chain length
      determination for these mutations including substitutions at the 1st and 9th
      amino acids upstream of the FARM that have not been reported previously. In
      addition, a mutation on a helix adjacent to the FARM within the substrate-binding
      pocket (D115G) suggests a novel mechanism for chain length determination. One
      mutant IspA clone carries a mutation of C155G at the 2nd amino acid upstream of
      conserved region IV (GQxxDL), which was recently found to be an important region
      controlling the chain elongation of a Type III GGPP synthase. One IspA clone
      carries mutations (T234A and T249I) near the conserved second aspartate rich
      motif (SARM). As a verification of the in vivo activity of the mutant clones
      (represented as C40 carotenoid formation), we confirmed the product distribution
      of wild-type and mutant IspA using an in vitro assay.

PMID- 15721808
TI  - Semi-synthetic DNA shuffling of aveC leads to improved industrial scale
      production of doramectin by Streptomyces avermitilis.
AB  - The avermectin analog doramectin (CHC-B1), sold commercially as Dectomax, is
      biosynthesized by Streptomyces avermitilis. aveC, a gene encoding an unknown
      mechanistic function, plays an essential role in the production of doramectin
      (avermectin CHC-B1), modulating the production ratio of CHC-B1 to other
      avermectins, most notably the undesirable analog CHC-B2. To improve the
      production ratio for doramectin, the aveC gene was subjected to iterative rounds
      of semi-synthetic DNA shuffling. Libraries of shuffled aveC gene variants were
      transformed into S. avermitilis, screened using a miniaturized 96-well growth and
      production format, and analyzed by high throughput mass spectrometry to determine
      CHC-B2:CHC-B1 ratios. Several improved aveC variants were identified; the best
      shuffled gene encoded 10 amino acid mutations, and conferred a final CHC-B2:CHC
      B1 ratio of 0.07:1, a 23-fold improvement over the starting gene (aveC wild
      type). Chromosomal insertion of an improved aveC shuffled gene into a high titer
      S. avermitilis strain yielded an improved doramectin production strain. This
      strain is under development to be used commercially, and is expected to provide
      considerable cost savings in large-scale manufacture, as well as significantly
      reducing by-product levels of CHC-B2 requiring disposal.

PMID- 15721809
TI  - Assay development and data analysis of receptor-ligand binding based on
      scintillation proximity assay.
AB  - In this paper, we described the optimization of a generic binding assay to
      measure ligand-receptor interactions for peroxisome proliferator-activated
      receptors (PPARs). The assay is based on scintillation proximity assay, in which
      a protein is coated on scintillant-incorporated beads, and a radiolabeled ligand
      stimulates the beads to emit a signal by binding to the immobilized protein. An
      intrinsic binding affinity of unlabeled ligands is determined by competitive
      displacement of the radioligand. The protein coating and ligand binding are
      achieved in one step by simply mixing ligands, protein and beads in sequence. No
      additional steps of pre-coating and washing of beads are required. Protein is
      captured on beads effectively by electrostatic interactions, thus no affinity
      labeling of protein is required. In data analysis, ligands are grouped into two
      classes based on their binding affinities. For tight binding ligands, an equation
      is derived to accurately determine the binding affinity. Otherwise a general
      equation applies. This quantitative and high throughput assay provides a tool to
      screen a large library of molecules in search of potent ligands.

PMID- 15721810
TI  - Parallel capillary electrophoresis for the quantitative screening of fermentation
      broths containing natural products.
AB  - Directed molecular evolution is a recursive process of controlled genetic
      diversification and functional screening. The success of this approach is
      dependent on both the quality of the genetic diversity and the ability to
      accurately screen a large population of individual genetic variants for those
      having improved function. In this paper, the application of parallel capillary
      electrophoresis to rapidly quantitate lovastatin production levels by Aspergillus
      terreus mutants is described. A parallel 96 capillary instrument analyzed 900
      samples in 8 h. with a 100 mM MES at pH 5.2 running buffer. In this manner, the
      fermentation broths of thousands of mutated strains were efficiently and
      inexpensively screened for increased lovastatin production. The ability to
      develop high-throughput methods to both separate and quantitate the components of
      complex mixtures greatly facilitates the ability to apply evolutionary
      engineering methods to complex biological systems.

PMID- 15721811
TI  - Measurement of GABA and glutamate in vivo levels with high sensitivity and
      frequency.
AB  - In the present protocol, we demonstrate a high-performance liquid chromatography
      (HPLC) system that enables detection of very low amounts of gamma-aminobutyric
      acid (GABA) (0.03 pmol) and glutamate (0.8 pmol). The HPLC system consists of two
      pumps, an electrochemical detector, a high-pressure six-way switching valve, a
      guard column, a microbore column, and a column oven. A microdialysis probe was
      implanted in the right parietal cortex in rats. Dialysates were collected every 5
      min and were split into two equal aliquots for separate analysis of GABA and
      glutamate. After derivatization with o-phthalaldehyde (OPA), samples were
      isocratically separated and purified by the guard column. To make the peak of
      GABA or glutamate appear in an opportune place in a chromatogram, a six-way
      switching valve was used to control the eluate containing GABA or glutamate to be
      led to the microbore column and electrochemical detector. By the use of this
      system, decrease in extracellular concentration of GABA, which precedes the
      appearance of electrical discharge initiated by hyperbaric oxygen (HBO2)
      exposure, was detected by microdialysis at the time resolution of 5 min.

PMID- 15721812
TI  - Random or selective neuroanatomical connectivity. Study of the distribution of
      fibers over two populations of identified interneurons in cerebral cortex.
AB  - We present a neuroanatomical tracing method in a stereological approach to study
      the proportional distribution of fibers of a particular projection over two
      chemically different populations of neurons. The fiber projection from the
      presubiculum to the medial division of the entorhinal cortex of the rat serves as
      a model projection. Potential target interneurons express calcium binding
      proteins, either parvalbumin or calretinin. The three markers were simultaneously
      stained in one and the same histological section. The procedure is according to a
      three-phase procedure, i.e., in vivo tracer injection phase, histology phase,
      laserscanning phase. Steps involved are: (1) Surgical application to the
      presubiculum (injection) of the neuroanatomical tracer, biotinylated dextran
      amine (BDA), with the purpose of labeling fibers innervating the entorhinal
      cortex. After surgery, transport of the tracer takes place during the one-week
      survival period; (2) Fluorescence detection of the labeled fibers through
      staining with fluorochromated avidin (avidin-Alexa Fluor 488 [green
      fluorescence]); (3) Simultaneous Immunofluorescence detection of two interneuron
      markers (using the appropriate primary antibodies and secondary antibodies
      conjugated to the fluorochromes Alexa Fluor 594 [red fluorescence] and Alexa
      Fluor 633 [infrared fluorescence]); (4) Acquisition of low-magnification images
      in a confocal laserscanning microscope and the preparation on a computer of a
      montage image covering the entire entorhinal cortex; (5) Overlaying this montage
      with a sampling grid; (6) Acquisition at high magnification of Z-series of
      confocal images in a statistical valid way based on this grid. Each marker was
      visualized in its own laser excitation/emission channel: 488, 568 and 647 nm; (7)
      Image processing and 3D reconstruction followed by evaluation of the results. The
      present approach can be used to examine whether or not a particular class of
      chemically identified neurons receives preferential innervation by a particular
      fiber projection.

PMID- 15721813
TI  - Disruption of immediate memory and brain processes: an auditory ERP protocol.
AB  - An event-related potential (ERP) protocol is described that can be used to
      investigate those sound-evoked neural processes that may be implicated in
      disrupting immediate memory. Conventional electroencephalogram (EEG) is recorded
      during the performance of a task that involves ignoring irrelevant sounds while
      trying to hold in memory lists of numbers. Specific bioelectric measures are made
      to prevent the contamination of recordings by the movements of articulators. An
      approach is also outlined which controls the timing of ERP components to sounds
      with different envelopes. Using this approach, it has been shown that the neural
      processes involved in the elicitation of the auditory N1 ERP response may be
      involved in the disruption of memory for serial order produced by irrelevant
      sound.

PMID- 15721814
TI  - The Suok ("ropewalking") murine test of anxiety.
AB  - In the present study, we suggest that long elevated horizontal rod (Suok test,
      ST) and its light-dark modification (LDST) may be used for behavioral
      characterization in mice, including simultaneous assessment of their anxiety,
      activity, and neurological phenotypes. To establish the ST and the LDST as murine
      models of anxiety, we used several different mouse strains which differ markedly
      in their anxiety and activity (C57BL/6, 129S1/SvImJ, NMRI, and BALB/c). Here we
      show that our tests are able to ethologically discriminate between high and low
      anxiety mouse strains, as assessed by horizontal and directed exploration, stops,
      and defecation boli. The spatial distribution of the LDST behaviors is also
      sensitive to these strain-specific anxiety phenotypes, showing clear avoidance of
      the brightly lit part of the test in stressed (rat exposed) vs. control NMRI
      mice. In addition, we validated the ST in 129S1/SvImJ and BALB/c mice by
      assessing the behavioral consequences of acute stress such as rat exposure.
      Finally, we showed that our test is able to detect high anxiety and poorer motor
      coordination in 129S1/SvImJ (vs. C57BL/6) mice. The results of our study show
      that the ST emerges as an experimental tool to analyze anxiety, motor-vestibular
      anomalies, as well as anxiety-induced motor impairments in mice. Overall, we
      suggest that the ST can be a useful protocol in neurobehavioral stress research
      including modeling stress-evoked states, pharmacological screening of potential
      anti-stress drugs, or behavioral phenotyping of genetically modified animals.

PMID- 15721815
TI  - Cryo-SEM and subsequent TEM examinations of identical neural tissue specimen.
AB  - Low temperature scanning electron microscopy of frozen-fractured specimens under
      cryo-protecting, non-dehydrating, and non-etching "wet" conditions, that is,
      direct cryo-SEM, was followed by transmission electron microscopy (TEM) with the
      same neural tissue specimens. In comparison to replica TEM, direct cryo-SEM can
      obtain images with a smooth gradation of contrast. The major advantage of direct
      cryo-SEM combined with TEM was that time was saved in SEM preparation. It had a
      high potentiality at a wide-range survey of multi-dimensional specimen structures
      with less-artifacts. Because the specimens were prepared as quickly as possible
      under "wet" conditions, the target structures could be examined under lower
      through higher magnifications. In the present study, neuronal and glial elements,
      such as plasma membranes and cell organelles that include the synaptic vesicles,
      were localized on the fractured surface. In subsequent TEM examination, it was
      confirmed that the underlying internal structures could be further characterized
      from cytological as well as molecular biological aspects. In addition, direct
      cryo-SEM distinctively demonstrated small intra-membrane particles (ca. 10 nm in
      diameter). However, due to electron lucency, they could not be confirmed in the
      re-processed TEM specimens. Applying the present protocol, stereological and
      internal architectural examinations of the neural tissues have been
      simultaneously conducted at ultra-fine levels.

PMID- 15721816
TI  - HistoGreen: a new alternative to 3,3'-diaminobenzidine-tetrahydrochloride
      dihydrate (DAB) as a peroxidase substrate in immunohistochemistry?
AB  - Abide its toxicity, 3,3'-diaminobenzidine-tetrahydrochloride-dihydrate (DAB) was
      the most potent marker for immunochemistry at the light and electron microscopic
      level in the last decades. Recently, a sensitive substrate for
      immunohistochemical staining methods and in-situ hybridization, HistoGreen, was
      developed for the use with peroxidase. In peroxidase reactions, HistoGreen
      delivers a green staining product which is suitable for permanent embedding
      without water. In contrast to DAB, HistoGreen is not toxic. To evaluate its
      usefulness, we performed comparative immunohistochemistry on angiotensin II (AT1)
      receptors with DAB- and HistoGreen-staining on paraffin embedded slices of the
      rat brain at the light microscopic level. This also included counterstaining with
      Mayer's Hemalum and Nuclear Fast Red, respectively. We could demonstrate that
      HistoGreen delivers a coarsely grained label which is fast detectable in light
      microscopy. HistoGreen equals DAB in the exact localization of the immunoreaction
      to a large degree but its reaction product is considerably less stable in alcohol
      and water than DAB. In combination with Nuclear Fast Red, HistoGreen provides
      excellent imaging properties for the visualization and documentation of
      immunoreactive structures paired with an adequate demonstration of cellular
      details. Its tendency towards rapid over-staining as well as its low stability
      will restrict the use of HistoGreen in some areas of immunohistochemical
      research, yet the new chromogen represents an interesting alternative to DAB at
      the light microscopic level.

PMID- 15721817
TI  - Detection of degeneration in rat sciatic nerve by in vivo near infrared
      spectroscopy.
AB  - We have recently developed an optical spectroscopy technique to monitor light
      scattering changes of the nervous system in vivo. Near infrared (NIR)
      spectroscopy emphasizes the detection of light scattering properties, which are
      prominent within the wavelength range of 700 to 850 nm wavelength. The purpose of
      this study is to test the hypothesis that demyelination and degeneration of the
      sciatic nerves after nerve injury will lead to a change in light scattering
      properties and be detected by the NIR technique. Left spinal nerve ligations (L4,
      L4 and L5, L5) were performed in rats. The scattering properties of the left
      (ligated) and right (control) sciatic nerve were measured by the NIR reflectance
      using a bifurcated needle probe at postoperative days 1, 4, 7, and 14. The
      results show that there was no significant difference among three types of
      ligation, and neither did the readings between left and right sciatic nerve at
      postoperative day 1. Significant decreases in light scattering indexes were found
      between left and right sciatic nerves at postoperative days 4, 7, and 14. It is
      concluded that our initial hypothesis is proven, suggesting that the NIR
      technique may have a potential for clinical application in detecting
      demyelination and degeneration of the nervous system.

PMID- 15721819
TI  - The opiate of the masses.

PMID- 15721818
TI  - Assays for measuring extracellular GABA levels and cell migration rate in acute
      slices.
AB  - The postnatal subventricular zone (SVZ) contains the largest pool of dividing and
      migrating neural precursors in the adult rodent brain. Neuronal precursors
      migrate throughout the SVZ and along the rostral migratory stream (RMS) towards
      the olfactory bulb where they differentiate into interneurons. To facilitate the
      investigation of cell migration in the SVZ and RMS, an inexpensive migration
      assay was developed for use in acute brain slices. Acute sagittal slices were
      kept at 37 degrees C in 5% O2/95% CO2-saturated solution and migrating cells in
      the SVZ and RMS were visualized using an upright infrared-differential
      interference contrast microscope. Time-lapse movies were acquired to identify the
      direction and measure the speed of cell migration. The neurotransmitter GABA and
      inhibitors of GABA receptors or transporters can be bath applied to determine the
      function of endogenous GABA on the direction and speed of cell migration. In
      parallel, the levels of endogenous GABA released from acute SVZ or RMS explants
      were measured with mass spectrometry. Additional techniques such as
      electrophysiology and immunohistochemistry confirmed the identity of cells as
      neuronal precursors and characterized the expression of GABA receptors and
      transporters. This report describes how modulations in the direction and speed of
      neuronal precursor migration can be accurately monitored and how changes in local
      GABA levels can be measured. The described techniques can be used to identify the
      endogenous factors that regulate cell migration. Identifying such factors is
      essential for the future therapeutic use of SVZ cells to replace damaged or lost
      cells.

PMID- 15721820
TI  - Devic's disease and autoantibodies.

PMID- 15721821
TI  - Evidence for cholinesterase-inhibitor therapy for dementia associated with
      Parkinson's disease.

PMID- 15721822
TI  - Minocycline in neurological diseases.

PMID- 15721823
TI  - Neurological infection in The Lancet Neurology.

PMID- 15721825
TI  - Tourette's syndrome: from behaviour to biology.
AB  - Tourette's syndrome (TS) is a chronic neuropsychiatric disorder characterised by
      motor and vocal tics. Diagnosis is based solely on clinical criteria. The
      prevalence of this syndrome is estimated to be between one and ten per 1000
      children and adolescents and the outcome is generally favourable; most patients
      improve by their late teens or early adulthood. Affected individuals are at
      increased risk of various comorbid neurobehavioural problems, the negative
      effects of which commonly exceed those of tics. Despite evidence that TS is an
      inherited disorder, the exact genetic abnormality is unknown. Environmental
      factors might have an important role in the expression of tics, and a
      poststreptococcal autoimmune cause has been proposed but is unproven. Brain
      imaging, neurophysiological, and post-mortem studies support involvement of
      cortical-striatal-thalamocortical pathways, but the definitive pathophysiological
      mechanism or neurotransmitter abnormality is unknown. Recent evidence, however,
      suggests a prefrontal dopaminergic abnormality. Traditional neuroleptics are the
      standard treatment for TS, but there is increasing interest in non-neuroleptic
      drugs, behavioural therapies, and surgical approaches.

PMID- 15721826
TI  - Tuberculous meningitis: many questions, too few answers.
AB  - Tuberculous meningitis (TM) is difficult to diagnose and treat; clinical features
      are non-specific, conventional bacteriology is widely regarded as insensitive,
      and assessment of newer diagnostic methods is not complete. Treatment includes
      four drugs, which were developed more than 30 years ago, and prevents death or
      disability in less than half of patients. Mycobacterium tuberculosis resistant to
      these drugs threatens a return to the prechemotherapeutic era in which all
      patients with TM died. Research findings suggest that adjunctive treatment with
      corticosteroids improve survival but probably do not prevent severe disability,
      although how or why is not known. There are many important unanswered questions
      about the pathophysiology, diagnosis, and treatment of TM. Here we review the
      available evidence to answer some of these questions, particularly those on the
      diagnosis and treatment of TM.

PMID- 15721827
TI  - Epilepsy and social identity: the stigma of a chronic neurological disorder.
AB  - Epilepsy is the most common serious neurological disorder worldwide, affecting
      about 50 million people. In most people with epilepsy, the disorder is clinically
      benign. However, because of the stigma associated with having epilepsy, which is
      common to many cultures, there can be a negative effect on the social identity of
      people with the disorder, particularly for those living in resource-poor
      countries. In this paper, we present general theories of stigma, as well as those
      specific to chronic illness. We relate these theories to the stigma associated
      with epilepsy throughout history and across cultures. We review research on the
      relation between stigma and the overall quality of life of people with epilepsy.
      Finally, we address reduction of the stigma.

PMID- 15721828
TI  - Genetics of intracranial aneurysms.
AB  - Subarachnoid haemorrhage (SAH) is a subtype of stroke caused by the rupture of an
      intracranial aneurysm. Genetic factors play an important part in the pathogenesis
      of SAH and intracranial aneurysms. SAH and intracranial aneurysms are complex in
      origin, involving the interaction of several genes and environmental factors. A
      disruption of the extracellular matrix of the arterial wall, which provides
      strength and elasticity to intracranial arteries, is a likely factor in the
      pathophysiology of intracranial aneurysms. In this review, we discuss the genetic
      association, linkage, and gene-expression studies of SAH and intracranial
      aneurysms. At present, four genome-wide linkage studies have identified genetic
      loci for intracranial aneurysms. Interestingly, three of these loci include
      functional candidate genes coding for structural proteins of the extracellular
      matrix. Of these genes, elastin and collagen type 1A2 are the most promising
      candidates, because allelic association with intracranial aneurysms has also been
      shown for these genes. However, variation in these two genes only explains a
      small proportion of the genetic factors involved in intracranial aneurysms.
      Future studies need to identify new candidate genes to help unravel the
      pathophysiology of the disorder.

PMID- 15721829
TI  - The Women's Health Initiative Memory Study: findings and implications for
      treatment.
AB  - BACKGROUND: The population of the developed world is ageing; consequently there
      is an increasing prevalence of age-related neuropsychiatric disorders, such as
      dementia of any cause and Alzheimer's disease (AD), for which few treatments are
      available. Observational studies suggested that hormone therapy (HT) might
      protect postmenopausal women against cognitive decline and AD. However, the
      results of randomised controlled trials in women age 65 years and older were
      negative. There has been extensive media coverage of these trials and many
      doctors are asked whether HT improves or worsens brain function in younger women
      who are prescribed HT for the treatment of menopausal symptoms. RECENT
      DEVELOPMENTS: The Women's Health Initiative Memory Study (WHIMS) was a
      multicentre, randomised, double-blind, placebo-controlled clinical trial in which
      a subgroup of women who participated in the Women's Health Initiative study were
      assessed for the effects of HT on dementia and mild cognitive impairment. There
      were two study arms, one involving 4532 postmenopausal women who received
      continuous combined oestrogen (conjugated equine oestrogens [CEE] plus
      medroxyprogesterone acetate) or placebo, and the other involving 2947
      hysterectomised women randomised to continuous unopposed CEE or placebo. All
      participants were age 65 years or older. CEE with or without medroxyprogesterone
      acetate, given to women age 65 years and older, does not protect against dementia
      or cognitive decline, but substantially increases the risk of dementia of any
      cause and cognitive decline. WHERE NEXT?: WHIMS answered critically important
      questions about whether HT can protect against dementia in elderly women who
      start HT some years after menopause. However, several clinically important
      questions are unanswered, including questions about the generalisability of WHIMS
      to groups of women for whom HT is an indication-perimenopausal women and those
      soon after menopause who have menopausal symptoms-and other methods of treatment
      delivery and treatment regimens.

PMID- 15721830
TI  - Infectious causes of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a serious chronic neurological disorder in which
      demyelination and inflammation occur in the white matter of the CNS. The findings
      of many epidemiological studies and a discordance of MS in monozygotic twins
      suggest that the disorder is acquired. The most likely cause is a virus because
      more than 90% of patients with MS have high concentrations of IgG, manifest as
      oligoclonal bands, in the brain and CSF. Most chronic inflammatory CNS disorders
      are infectious. More indirect evidence that MS is caused by a virus is the
      association of several viruses with demyelinating encephalomyelitis in human
      beings, and the induction of demyelination in animals infected with viruses in
      research. Nevertheless, no virus has been isolated from the brains of patients
      who had MS. Molecular analysis of IgG gene specificity in the brain and CSF of
      those with MS has shown features of an antigen-driven response: clonal
      amplification and extensive somatic mutations. A viral antigen against which the
      IgG in MS brain and CSF is directed might be identified.

PMID- 15721831
TI  - Targeting cell regulation promotes pathogen survival in macrophages.

PMID- 15721832
TI  - Turning Yersinia pathogenesis outside in: subversion of macrophage function by
      intracellular yersiniae.
AB  - Three bacterial species within the genus Yersinia are causative agents of human
      disease. Yersinia pestis is transmitted by fleas or in aerosols, infects regional
      lymph nodes or lungs, and causes the highly lethal disease known as plague.
      Yersinia enterocolitica and Yersinia pseudotuberculosis are enteric pathogens
      most commonly associated with self-limiting infections of the mesenteric lymph
      nodes. Although Y. pestis and the enteropathogenic Yersinia species utilize
      different modes of transmission and cause different diseases, they rely on a
      common set of "core" virulence determinants to successfully infect a mammalian
      host. These virulence factors are encoded on the bacterial chromosome and on an
      approximately 70-kb plasmid. Once established in lymphoid tissue, all three
      Yersinia species replicate as aggregates of extracellular bacteria within
      necrotic lesions or abscesses. At this stage of the infectious process, the
      bacteria resist phagocytosis by neutrophils, which are able to destroy the
      bacteria if they are internalized. A type III secretion system encoded on the 70
      kb plasmid functions to export multiple proteins (the Yops and LcrV) that are
      delivered to the extracellular milieu, the plasma membrane, or the cytosol of a
      host target cell. The Yops and LcrV act in concert to inhibit phagocytosis and
      downregulate inflammation. Although it is clear that the bulk of bacterial
      multiplication occurs in an extracellular phase, there is also evidence that all
      three pathogenic Yersinia survive and multiply in macrophages. Survival and
      replication of Yersinia in macrophages may occur throughout the infection, but is
      likely to be of greatest importance at early stages of colonization. That
      macrophages can serve as permissive sites for bacterial replication in vivo is
      supported by in vitro experiments, which demonstrate that Y. pestis, Y.
      peudotuberculosis, and Y. enterocolitica share the ability to survive and
      multiply in macrophage phagosomes. There is also evidence that the bacteria can
      subvert the functions of macrophages from within, by inhibiting phagosome
      acidification (Y. pseudotuberculosis) and the production of nitric oxide (Y.
      pestis and Y. pseudotuberculosis). Although considerable attention has been
      focused on how Yersinia subverts the functions of phagocytes from the outside,
      the study of how these bacteria subvert macrophage functions from the inside will
      lead to a better overall understanding of Yersinia pathogenesis.

PMID- 15721833
TI  - Cellular bioterrorism: how Brucella corrupts macrophage physiology to promote
      invasion and proliferation.
AB  - Brucellosis is a worldwide human zoonosis caused by intracellular bacteria of the
      genus Brucella. Virulence factors play an important role in allowing Brucella
      infection and proliferation within macrophages. Brucella enters macrophages
      through lipid raft microdomains, avoids phagolysosome fusion, and inhibits TNF
      alpha secretion and apoptosis. Furthermore, Brucella can perturb bactericidal
      activity in macrophages by influencing the host cell response to its advantage
      through its LPS or by activating the cAMP/PKA pathway. To date, small steps have
      been taken in defining and understanding the virulence factors of Brucella used
      in macrophage subversion, but further investigation is required to fully explain
      virulence and persistence.

PMID- 15721834
TI  - Mechanisms of mycobacterial persistence in tuberculosis.
AB  - Tuberculosis is one of the world's most devastating diseases, with more than two
      million deaths and eight million new cases occurring annually. Mycobacterium
      tuberculosis evades the innate antimicrobial defenses of macrophages by
      inhibiting the maturation of its phagosome to a bactericidal phagolysosome.
      Phagosome maturation is dependent on macrophage Ca(2+) signaling, which results
      in the recruitment of cytosolic calmodulin (CaM) to the phagosome membrane and
      subsequent focal activation of CaM kinase II (CaMKII). M. tuberculosis blocks
      this process via inhibition of a macrophage enzyme, sphingosine kinase, which is
      a proximal generator of Ca(2+) signaling during phagocytosis. This results in a
      failure of assembly of the Ca(2+)/CaM/CaMKII signaling complex on the membrane of
      the mycobacterial phagosome and the bacilli's persistence and replication in a
      protective intracellular niche. Pharmacologic or physiologic reversal of this
      inhibition of macrophage Ca(2+) signaling restores the normal sequence of
      phagosome maturation, resulting in decreased intracellular viability of M.
      tuberculosis.

PMID- 15721835
TI  - Targeting of the actin cytoskeleton during infection by Salmonella strains.
AB  - Many bacterial pathogens produce virulence factors that alter the host cell
      cytoskeleton to promote infection. Salmonella strains target cellular actin in a
      carefully orchestrated series of interactions that promote bacterial uptake into
      host cells and the subsequent proliferation and intercellular spread of the
      organisms. The Salmonella Pathogenicity Island 1 (SPI1) locus encodes a type III
      protein secretion system (TTSS) that translocates effector proteins into
      epithelial cells to promote bacterial invasion through actin cytoskeletal
      rearrangements. SPI1 effectors interact directly with actin and also alter the
      cytoskeleton through activation of the regulatory proteins, Cdc42 and Rac, to
      produce membrane ruffles that engulf the bacteria. SPI1 also restores normal
      cellular actin dynamics through the action of another effector, SptP. A second
      TTSS, Salmonella Pathogenecity Island 2 (SPI2), translocates effectors that
      promote intracellular survival and growth, accompanied by focal actin
      polymerization around the Salmonella-containing vacuole (SCV). A number of
      Salmonella strains also carry the spv virulence locus, encoding an ADP-ribosyl
      transferase, the SpvB protein, which acts later during intracellular infection to
      depolymerize the actin cytoskeleton. SpvB produces a cytotoxic effect on infected
      host cells leading to apoptosis. The SpvB effect appears to promote intracellular
      infection and may facilitate cell-to-cell spread of the organism, thereby
      enhancing virulence.

PMID- 15721836
TI  - Modulation of phagolysosome biogenesis by the lipophosphoglycan of Leishmania.
AB  - Promastigotes of the protozoan parasite Leishmania are inoculated into the
      mammalian host by an infected sandfly and are phagocytosed by macrophages. There,
      they differentiate into amastigotes, which replicate in phagolysosomes. A family
      of glycoconjugates, the phosphoglycans (PGs), plays an important role in the
      ability of promastigotes to survive the potentially microbicidal consequences of
      phagocytosis. Lipophosphoglycan (LPG), an abundant promastigote surface
      glycolipid, has received considerable attention over the past several years. Of
      interest for this review, lipophosphoglycan confers upon Leishmania donovani
      promastigotes the ability to inhibit phagolysosome biogenesis. This inhibition
      correlates with an accumulation of periphagosomal F-actin, which may potentially
      form a physical barrier that prevents L. donovani promastigote-harboring
      phagosomes from interacting with late endosomes and lysosomes. Thus, similar to
      several other pathogens, Leishmania promastigotes hijack the host cell's
      cytoskeleton early during the infection process. Here, we review this phenomenon
      and discuss the potential underlying mechanisms.

PMID- 15721837
TI  - Leishmania donovani engages in regulatory interference by targeting macrophage
      protein tyrosine phosphatase SHP-1.
AB  - Protozoan parasites of the genus leishmania are obligate intracellular parasites
      of monocytes and macrophages. These pathogens have evolved to invade the
      mammalian immune system and typically survive for long periods of time.
      Leishmania have developed a variety of remarkable strategies to prevent their
      elimination by both innate and acquired immune effector mechanisms. One
      particular strategy of interest involves manipulation of host cell regulatory
      pathways so as to prevent macrophage activation required for efficient
      microbicidal activity. These interference mechanisms are the main focus of this
      review. Several lines of evidence have been developed to show that the Src
      homology-2 domain containing tyrosine phosphatase-1 (SHP-1) becomes activated in
      leishmania-infected cells and that this contributes to disease pathogenesis.
      Recent studies aimed at understanding the mechanism responsible for the change in
      activation state of SHP-1 led to the identification of leishmania EF-1alpha as an
      SHP-1 binding protein and SHP-1 activator. This was a surprising finding given
      that this ubiquitous and highly conserved protein plays an essential role in
      protein translation in both prokaryotic and eukaryotic cells. The role of
      leishmania EF-1alpha as an SHP-1 activator and its contribution to pathogenesis
      are reviewed with particular attention to the properties that distinguish it from
      host EF-1alpha.

PMID- 15721838
TI  - A comparison of the pro-inflammatory, NF-kappaB-dependent cytokines: TNF-alpha,
      IL-1-alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus
      patients.
AB  - To explore the feasibility of detection of the level of NF-kappaB-dependent
      cytokines in oral fluids from patient with oral lichen planus (OLP) for clinical
      application, 13 OLP subjects were enrolled in the study as were 13 age-sex
      matched controls. In each subject, the whole unstimulated saliva (WUS), mixture
      of saliva and isotonic saline oral rinse (Saliva-NaCl), and lesion tissue
      transudates (TT) were collected by standard techniques. The level of cytokines,
      TNF-alpha, IL-1-alpha, IL-6, and IL-8 in three types of oral fluids was
      determined by ELISA. In the three types of oral fluids, a significantly higher
      level of these cytokines was detected in OLP patients than in normal controls.
      These results indicate that NF-kappaB-dependent inflammatory cytokines may be
      detected at increased levels in certain oral fluids which may have diagnostic and
      prognostic potential for monitoring disease activity and making therapeutic
      decisions in patients with OLP.

PMID- 15721839
TI  - Chronic idiopathic urticaria: infiltrating cells and related cytokines in
      autologous serum-induced wheals.
AB  - The term chronic autoimmune urticaria (CAIU) is used for chronic urticaria in
      subjects who present a whealing response to the intradermal injection of
      autologous serum, suggesting the presence of pathogenic antibody activities. In
      this study, we examined 28 chronic urticaria subjects with positive autologous
      serum skin test (ASST), all of whom presented autologous serum-induced lesions at
      different evolutive stages. Punch biopsies were taken from lesional skin of six
      subjects at 10', eight subjects at 30', six subjects at 60', and four subjects
      each at 24 and 48 h. Immunological studies focussed on infiltrating cell
      immunophenotype and related cytokines, chemokines and chemokine receptors,
      adhesion molecules. Immunohistochemical staining was performed to measure
      expression of CD3, CD4, CD8, tryptase, eosinophil cationic protein,
      myeloperoxidase, basophil granular protein, IL-4, IL-5, IL-8, CCR3 and CXCR3,
      ICAM-1, VCAM and ELAM. Control staining was done on unaffected skin from the
      patients and normal skin from four healthy donors. The main infiltrating
      population was represented by neutrophils, seen focally in both unaffected skin
      (P = 0.001) and healthy controls (P = 0.003). IFN-gamma and IL-5 were expressed
      focally in autologous wheals. Significant staining for IL-4 was seen at 30'. CCR3
      and CXCR3 were expressed less in autologous wheals than in uninvolved skin (P <
      0.0001; P = 0.002). Cellular adhesion molecules (CAMs) reached their highest
      expression at 30' and 60' in induced lesions, and they showed strong expression
      also in unaffected skin (ICAM-1: P < 0.0001). Our data show that the
      immunoinflammatory features of ASST-induced wheals involve a prevalent role of
      lymphocytes (with a mixed Th1/Th2 response), with strong neutrophil infiltration
      and activity and involvement of the chemokine pathway. We interpreted the finding
      of inflammatory cells and mediator up-regulation in uninvolved CIU skin as a sign
      of prolonged and widespread "urticarial status".

PMID- 15721840
TI  - Endotoxemia enhances expression of the signaling receptor (GP130) on protein and
      molecular level.
AB  - Interleukin 6 (IL-6) performs a prominent role during sepsis. To examine the
      molecular regulation of IL-6, IL-6 receptor, and signaling receptor gp130 during
      endotoxemia, nine healthy young volunteers received a bolus injection of
      lipopolysaccharide (LPS) on day 1 and saline on day 2 in a double blind,
      randomized, placebo-controlled trial. LPS enhanced IL-6 release 300-fold. IL-6
      mRNA expression was not significantly altered in blood samples at any time after
      LPS infusion in vivo, while incubation of whole blood with 50 pg/ml LPS up
      regulated IL-6 mRNA levels 8000- to 50,000-fold in vitro. LPS infusion increased
      synthesis of gp130 mRNA 5.5-fold compared to baseline at 4 h (P < 0.05), while no
      significant change was observed in the placebo period (P = 0.001 between groups).
      LPS increased the percentage of gp130 positive neutrophils gp130 700% over
      baseline at 8 h (P < 0.01 versus baseline and placebo). IL-6 receptor levels were
      not significantly altered by low-grade endotoxemia. In conclusion, endotoxemia up
      regulates gp130 expression in vivo and in vitro. Quantification of IL-6 mRNA
      expression in circulating leukocytes is unlikely a suitable marker for monitoring
      of endotoxemia.

PMID- 15721841
TI  - Effect of targeted disruption of signal transducer and activator of transcription
      (Stat)4 and Stat6 genes on the autoimmune diabetes development induced by
      multiple low doses of streptozotocin.
AB  - The MLDS (multiple low doses of streptozotocin) model of diabetes was induced in
      Stat4(-/-), Stat6(-/-), and double-deficient Stat4(-/-)/6(-/-) mice to examine
      the role of STAT4/STAT6 deficiency in development of autoimmune diabetes.
      Cytokine production of T-cells from Stat4(-/-) mice confirmed a predominantly Th2
      type immune response. Stat4(-/-) mice exhibited delayed onset and reduced
      severity of disease compared to wild-type (WT) mice. In contrast, STAT6
      deficiency, with a predominant Th1 response, did not influence the kinetics or
      severity of MLDS-induced autoimmune diabetes. Interestingly, Stat4(-/-)/6(-/-)
      mice, with a prominent Th1-type response, experienced an accelerated and
      aggravated course of diabetes after MLDS, implicating a STAT4-independent Th1
      response in the immunopathogenesis of MLDS-induced autoimmune diabetes. The
      sensitivity of islet cells from Stat4(-/-) or Stat4(-/-)/6(-/-) mice to cytokines
      and STZ was not different from that of islet cells of WT mice. Hence, the
      observed effects of STAT4 and STAT4/6 deficiency on MLDS-induced autoimmune
      diabetes are likely due to their effects on T-cell responses.

PMID- 15721842
TI  - Functionally divergent T lymphocyte responses induced by modification of a self
      peptide from a tumor-associated antigen.
AB  - The N- and C-terminal flanking domains of the invariant chain peptide, CLIP, have
      remarkable immunological properties. Addition of these flanking domains to a
      foreign peptide antigen increases its immunologic potency. The present studies
      evaluated whether altering a peptide ligand from the tumor-associated antigen c
      neu with the flanking domains of CLIP could modify the systemic immune response.
      The results indicate that the immunogenicity of an MHC class II restricted
      peptide (NEU) derived from c-neu was significantly altered by addition of the
      flanking domains from CLIP. Interestingly, selective modification of the peptide
      with either the N- or the C-terminal flanking domains resulted in functionally
      divergent systemic immune responses. Immunization of normal F344 rats with the
      NEU peptide modified with the N-terminal domain of CLIP (N-NEU) resulted in an
      immune response primarily consisting of type 1 (IL-2, IFNgamma) cytokine
      producing T cells. On the other hand, type 2 (IL-4) cytokine responses were
      largely predominant following immunization with the self-peptide modified with
      the C-terminal flanking domain (NEU-C). The functionally divergent responses
      elicited by the modified self-peptides were accompanied by significant changes in
      the expression of the CD28/CTLA4/B7 family of co-stimulatory molecules.
      Immunization with the N-NEU peptide led to enhanced expression of CD28 in the
      antigen-specific, CD4+ T cell compartment while expression of B7.1 was
      dramatically reduced in antigen-specific CD8+ T cells. Comparatively, expression
      of CTLA4 was down-regulated in the antigen-specific CD4+ T cell compartment
      following immunization with NEU-C peptide. The N-NEU peptide also had a direct
      effect on dendritic cells leading to the up-regulation of B7.1 expression. Taken
      together, functionally divergent systemic immune responses can be elicited by
      strategically altering a self-peptide ligand with the N- and C-terminal flanking
      domains of CLIP. Moreover, changes in expression of co-stimulatory molecules that
      are required for T cell activation and T cell-T cell communication may account
      for the polarization of the immune response elicited by the chimeric peptides.

PMID- 15721843
TI  - Anti-inflammatory effects of UV-irradiated lymphocytes: induction of IL-1Ra upon
      phagocytosis by monocyte/macrophages.
AB  - One of the mechanisms proposed to explain immunomodulatory actions of ultraviolet
      light (UV) is production of endogenous anti-inflammatory cytokines. The purpose
      of the present study is to evaluate how UV light affects the production of IL-10
      and IL-1Ra and to provide insight as to the role of phagocytosis of apoptotic
      lymphocytes in this process. Cytokine production was evaluated in a coculture
      system consisting in UV-treated lymphocytes in the presence of autologous PBMC.
      The impact of phagocytosis was tested by two blocking agents cytochalasin E and
      anti-CD36 mAb. The apoptotic process affecting irradiated lymphocytes was
      progressive, culminating at 48 h. To achieve significant cytokine production,
      irradiated lymphocytes were incubated overnight at 37 degrees C. Coculture of
      apoptotic lymphocytes with autologous PBMC resulted in a significant increase of
      IL-1Ra mRNA (+340%; P = 0.001) and protein (+72%; P = 0.001) production. This
      synthesis was blocked by cytochalasin E but upregulated by CD36 receptor cross
      linking. Our study shows that UV light induces lymphocyte apoptosis followed by
      its phagocytosis by monocyte/macrophages, a step that preferentially activates IL
      1Ra.

PMID- 15721845
TI  - Nitric oxide synthase gene G298 allele. Is it a marker for microvascular angina
      in hypertensive patients?
AB  - BACKGROUND: Nitric oxide (NO) has an important effect on blood pressure, arterial
      wall, and the basal release of endothelial NO in hypertension (HPN) may be
      reduced. Until now, there is no solid data revealing the potential role of the
      polymorphism of the nitric oxide synthase gene (NOS) in patients with HPN and
      microvascular angina. AIM: The aim of the present study is to investigate the
      gene of endothelial nitric oxide synthase (eNOS), as the polymorphism of this
      gene may be a putative candidate for HPN and initiate the process of
      atherosclerosis. METHODS: Sixty participants were recruited for this study; 50
      were hypertensive patients complaining of chest pain [30 of them have
      electrocardiogram (EKG) changes of ischemia], 20 had isolated HPN, and 10 healthy
      volunteers served as control. All patients underwent stress myocardial perfusion
      imaging (MPI) and coronary angiography. Genotyping of eNOS for all patients and
      controls was performed. The linkages between HPN, microvascular angina and eNOS
      gene polymorphism were investigated. RESULTS: MPI and coronary angiography
      revealed that 15 patients had chest pain with true ischemia and reversible
      myocardial perfusion defects (multiple and mild) but normal epicardial coronary
      arteries (microvascular angina), while 15 patients had significant coronary
      artery disease (CAD), and 20 hypertensive patients showed normal perfusion scan
      and coronary angiography. The prevalence of the NOS G(298) allele was higher in
      the hypertensive group with microvascular angina (documented by MPI) than it was
      among the control participants (P<.005). The eNOS allele was significantly higher
      in the hypertensive group than in the control participants, but there was no
      significant difference in homozygote mutants among hypertensive participants, x
      syndrome and patients with CAD. CONCLUSION: eNOS gene polymorphism is proved to
      be an important etiology in microvascular angina (x-syndrome) among hypertensive
      patients. In addition, the eNOS mutant gene showed a significant increase in
      isolated HPN and in patients with CAD.

PMID- 15721844
TI  - Clinical and angiographic profile of patients with markedly elevated coronary
      calcium scores (>or=1000) detected by electron beam computed tomography.
AB  - OBJECTIVE: The objective of this study was to determine the clinical and
      angiographic profile of patients with extremely high coronary artery calcium
      scores (CACS; >or=1000) by electron beam computed tomography (EBCT). METHODS: All
      patients at Rush University Medical Center who had a calcium score >or=1000 and a
      coronary angiogram performed from 1997 to 2002 were identified using a
      prospectively collected database. The baseline demographics, symptom status, and
      degree of coronary stenosis by angiography and subsequent rate of coronary
      intervention were compared with that of patients with calcium scores <1000.
      RESULTS: The clinical and angiographic profile of patients with severe coronary
      calcification, detected by EBCT, revealed that patients with scores >or=1000 had
      a significantly higher prevalence of coronary stenosis >or=50% compared with
      patients with scores <1000 (97% vs. 57%, P<.001). The group with CACS >or=1000
      was more likely to be male (90% vs. 75%, P=.027) and was older (64+/-8 vs. 59+/
      10, P=.001) compared with the group with less severe calcification. Although
      there was a significantly higher rate of luminal stenosis detected by coronary
      angiography in the cohort with CACS >or=1000, there was no difference in
      subsequent percutaneous coronary intervention (PCI) and utilization of
      intracoronary stents between the two groups. CONCLUSIONS: A markedly elevated
      coronary calcium score (>or=1000) is correlated with increasing age and is
      associated with an increased likelihood of coronary stenosis >or=50%. However,
      the decision to perform coronary angiography in patients with severe coronary
      calcification should not be based solely on these findings, but should remain
      primarily dependent on the degree of ischemia detected by clinical and functional
      assessment.

PMID- 15721846
TI  - Proliferation and beta-tubulin for human aortic endothelial cells within gas
      plasma scaffolds.
AB  - PURPOSE: We determined if human aortic endothelial cells (HAEC) enhanced
      proliferative and angiogenic phenotypes within gas-plasma treated bioresorbable
      D,L-polylactic acid (D,L-PLA) three-dimensional scaffolds. METHOD: 6 x 10(3) HAEC
      (N=120) were incubated for 6, 12 or 18 days within either non-treated control or
      treated scaffolds. Before removing media, unstained wells were observed for
      apparent cell densities. Quantitative colorimetric WST-1 mitochondrial assays
      were determined for pooled conditioned media from both HAEC attached to wells and
      their respective HAEC-containing scaffolds. Fixed HAEC in scaffolds were examined
      using non-quantitative laser confocal microcopy with FITC-conjugated consensus,
      Types-I/II or Type-III beta-tubulin. RESULTS: WST-1 indicated that significantly
      (p<0.05) less mitochondria were on cell culture plates than inside scaffolds but
      for different reasons. For example, a 12-18 days comparison between WST-1 and
      beta-tubulin indicated that wells decreased because of overgrowth apotosis;
      whereas, mitochondrial activity inside treated scaffolds decreased with increased
      tubulogenesis. Observed with consensus and Type-I/II beta-tubulin, HAEC-treated
      scaffolds exhibited increased cell-cell interconnections and angiogenic cords
      undergoing tubulogenesis to form vessels with central lumens as well as increased
      Type-III beta-tubulin, predominantly in cells of smaller surface areas. Moreover,
      beta-tubulin inside HAEC-treated scaffolds appeared in discrete cytoskeletal and
      podial regions; yet, beta-tubulin for HAEC-control scaffolds was located in more
      diffuse cytoplasmic regions especially at 18 days. CONCLUSIONS: HAEC-treated
      scaffolds undergo increased migration, proliferation, beta-tubulin expression and
      quiescent cord formation. HAEC in scaffolds represent a potential model to study
      mechanisms for vascular cord progression into tubes. WST-1 does not represent
      accurate cell densities in three-dimensional scaffold matrices.

PMID- 15721847
TI  - Transepicardial autologous bone marrow-derived mononuclear cell therapy in a
      porcine model of chronically infarcted myocardium.
AB  - OBJECTIVE: Cell therapy is becoming a viable strategy to improve
      revascularization and myocardial function after myocardial injury. We evaluated
      the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on
      collateral vessel development and myocardial function in a porcine model of
      chronically infarcted heart. METHODS: Myocardial infarction was produced in 13
      domestic swine. At 4 weeks, animals were randomized to receive transepicardial
      injections of autologous BMMNCs (approximately 24x10(6) cells, n=8) or phosphate
      buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral
      growth, angiogenesis, and infarct size were assessed by angiography,
      immunohistochemistry, and histomorphometry. RESULTS: Regional contractility was
      assessed by transepicardial echocardiography at baseline and 4 weeks following
      treatment. Angiography revealed a trend toward increased collateral growth in the
      BMMNC group. Wall motion score index (myocardial function) was similar in both
      groups at baseline (1.63+/-0.16 vs. 1.25+/-0.25, P=.21) and at 4 weeks (1.83+/
      0.22 vs. 1.63+/-0.38, P=.62). alpha-Actin-positive smooth muscle cells (SMCs) and
      Factor VIII positive endothelial cells were significantly greater in the BMMNC
      injected animals (314.8+/-37.4/0.1 vs. 167.1+/-11.9/0.1 mm(2) in controls, P=.02,
      and 363.3+/-28.2 cells/0.1 mm(2) vs. 254.4+/-28.1 cells/0.1 mm(2) in controls,
      P=.03, respectively). The number of blood vessels >50 mum in diameter was
      significantly increased in the BMMNC group (317.9+/-54.9 vs. 149.1+/-6.1, P<.05).
      The size of the infarct area was smaller in the BMMNC-transplanted group than in
      the controls (P=.015). CONCLUSION: BMMNC transplantation appears to improve
      angiogenesis and reduce infarct size yet results in no improvement in left
      ventricular function in a chronically infarcted heart.

PMID- 15721848
TI  - The effect of percutaneous transmyocardial laser revascularization on left
      ventricular function in a porcine model of hibernating myocardium: a pilot study.
AB  - BACKGROUND: Hibernating myocardium is defined as a state of persistently impaired
      myocardial function at rest due to reduced coronary blood flow that can partially
      or completely be restored to normal if the myocardial oxygen supply/demand
      relationship is favorably altered. Percutaneous laser revascularization (PMR) is
      an emerging catheter-based technique that involves creating channels in the
      myocardium, directly through a percutaneous approach with a laser delivery
      system, and has been shown to reduce symptoms in patients with severe refractory
      angina; however, its effect on improving regional wall motion abnormalities in
      hibernating myocardium has not been clearly established. We sought to determine
      the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular
      function in a porcine model of hibernating myocardium. METHODS: A model of
      hibernating myocardium was created by placement of an ameroid constrictor in the
      proximal left anterior descending artery of a 35 kg male Yorkshire pig. The
      presence of hibernating myocardium was confirmed with dobutamine stress
      echocardiography (DSE) and defined as severe hypocontractility at rest, with an
      improvement in systolic wall thickening with low-dose dobutamine in myocardial
      regions with a subsequent deterioration in function at peak stress (biphasic
      response). After the demonstration of hibernating myocardium, PMR was performed
      in the area of hypocontractile function, and the serial echocardiography was
      performed. The echocardiograms were reviewed by an experienced echocardiologist
      blinded to the results, and regional wall motion was assessed using the American
      Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal
      was sacrificed and the heart sent for histopathologic studies. RESULTS: A
      comparison of the regional wall motion function of the area distal to the ameroid
      constrictor and in the contralateral wall at baseline, post-ameroid placement,
      and post-PMR was performed. Hibernating myocardium was demonstrated 4 weeks after
      ameroid placement by DSE. Coronary angiography demonstrated a discrete
      90%stenosis in the proximal LAD at the site of ameroid constrictor placement
      without evidence of collaterals. Using PMR, 17 bursts were successfully delivered
      to the anterior wall distal to the ameroid constrictor. Four weeks after PMR,
      there was improvement in wall motion function in the region distal to the ameroid
      placement by echocardiography. Histopathologic analysis demonstrated the absence
      of myocardial infarction in the anterior wall distal to the ameroid constrictor.
      CONCLUSIONS: The performance of PMR in a porcine model of hibernating myocardium
      is feasible and is associated with an improvement regional wall motion function
      after 4 weeks.

PMID- 15721849
TI  - Effect of ionizing radiation on the stability and performance of the TAXUS
      Express2 paclitaxel-eluting stent.
AB  - BACKGROUND: The advent of drug-eluting stents has provided the interventional
      cardiologist an effective new tool in treating coronary restenosis. There
      remains, however, a small group of patients that still require intervention
      following drug-eluting stent therapy. Currently, intravascular brachytherapy
      (IVBT) is approved for use in the treatment of in-stent restenosis (ISR). This
      study investigated the effect of gamma and beta radiation doses typically used in
      IVBT on the performance of the TAXUS Express(2) paclitaxel-eluting stent. METHODS
      AND RESULTS: It was determined that there were no statistically significant
      changes to in vitro paclitaxel release from stent exposed to radiation compared
      to controls subjected to the same conditions except for the radiation exposure.
      The molecular weight of the Translute polymer carrier matrix and the level of
      paclitaxel degradants were not changed following exposure to radiation doses up
      to twice what is typically used in IVBT. Beta and gamma radiation doses typically
      used in IVBT had no significant effect on the Translute polymer carrier,
      paclitaxel degradation, or paclitaxel release in this in vitro model. CONCLUSION:
      The data are encouraging and support further evaluation of the use of IVBT in the
      treatment of ISR in the presence of drug-eluting stents.

PMID- 15721850
TI  - Effects of vessel curvature on dose distributions in catheter-based intravascular
      brachytherapy for various radionuclides.
AB  - PURPOSE: When radioactive sources are used to treat restenosis, the blood vessels
      are usually curved. In catheter-based intravascular brachytherapy systems, this
      curvature introduces dose deviations from the idealized situation used for
      treatment planning, in which both blood vessels and sources are assumed to be
      straight. Because of the different depth characteristics of different
      radionuclides, it is foreseeable that the curvature effects on dosimetry might
      vary with the different types of radionuclides. In this study, curvature effects
      on dose distributions along and around a blood vessel were investigated for
      different gamma and beta emitters. MATERIALS/METHODS: A blood vessel was modeled
      as a cylinder that could be curved as a circular arc of different degrees. Dose
      calculations were performed on the cylindrical surfaces of the model vessel for
      the radioactive sources of (192)Ir, (125)I, (103)Pd, (188)Re, (32)P, and
      (90)Y/Sr. The radius of the vessel was assumed to be 1.0, 1.5, 2.0, and 2.5 mm,
      respectively. A catheter-based radiation delivery system was simulated to consist
      of a line source with a length of 2 cm. The dose rate at a point in space
      produced by the radioactive source was computed by integrating the point dose
      rate kernel of the corresponding radionuclide over the entire radioactive line,
      which was assumed to curve with the blood vessel along its central axis.
      Dosimetric calculations were performed for different curvature angles. The
      curvature effects on the dosimetry were characterized with two quantities, LDU
      and ADU, where LDU described the longitudinal dose uniformity (LDU) along blood
      vessels and ADU described the azimuthal dose uniformity (ADU) from the expected
      delivery dose around blood vessels. RESULTS: Vessel and source curvatures barely
      changed the LDU for the gamma emitters (within 2%). The curvature effects on the
      LDU were relatively larger for the beta emitters (less than 5%). The dose
      deviations caused by curvature around a blood vessel were more significant.
      Depending on the radius of the vessel and degree of curvature, the deviation
      could be as much as 25% for the gamma emitters and 30% for the beta emitters. The
      curvature effects became larger with the increase of vessel radius and,
      obviously, with the increase of curvature. There seemed to be no significant
      differences in the curvature effects among different types of gamma emitters and
      among different types of beta emitters. CONCLUSIONS: Curvature-induced effects on
      dose distribution are similar for both the gamma and the beta emitters. The LDU
      along the vessels does not change significantly with curvature. The dose changes
      around the vessels are more pronounced and can be as high as 30%.

PMID- 15721851
TI  - Radial artery approach facilitates percutaneous coronary angioplasty of ectopic
      downward origin of the right coronary artery from the opposite sinus.

PMID- 15721852
TI  - "Hybrid" approach for the treatment of a giant left main coronary artery
      aneurysm.

PMID- 15721853
TI  - Symbols within words: have we neglected the AdeNOsine A2 receptor?

PMID- 15721854
TI  - Role of integrins, including alpha8, for neointima formation after vascular
      injury.

PMID- 15721855
TI  - Tetrahydrobiopterin and eNOS dimer/monomer ratio--a clue to eNOS uncoupling in
      diabetes?

PMID- 15721856
TI  - Peroxisome proliferator-activated receptor beta/delta: a new antihypertrophic
      drug target?

PMID- 15721857
TI  - Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury,
      inflammation and shock.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand
      activated transcription factor belonging to the nuclear hormone receptor
      superfamily. PPAR-gamma regulates gene expression by forming a heterodimer with
      the retinoid X receptor (RXR) before binding to sequence-specific PPAR response
      elements (PPREs) in the promoter region of target genes, thereby regulating
      several metabolic pathways, including lipid biosynthesis and glucose metabolism.
      Thiazolidinediones (TZDs, i.e. rosiglitazone, pioglitazone), which are synthetic
      PPAR-gamma agonists, act as insulin sensitizers and are used in the treatment of
      type 2 diabetes. In the last few years, it has, however, become evident that the
      therapeutic effects of PPAR-gamma ligands reach far beyond their use as insulin
      sensitizers. Recently, PPAR-gamma has been implicated as a regulator of cellular
      inflammatory and ischemic responses. PPAR-gamma agonists may exert their anti
      inflammatory effects by negatively regulating the expression of pro-inflammatory
      genes induced during macrophage differentiation and activation, by either PPAR
      gamma-dependent or -independent mechanisms. Several lines of evidence suggest
      that TZDs protect the heart and other organs against the tissue injury caused by
      ischemia/reperfusion (I/R) injury and shock. This review discusses the anti
      inflammatory signalling pathways activated by PPAR-gamma, as well as the
      potential therapeutic effects of PPAR-gamma agonists in animal models of
      ischemia/reperfusion, inflammation and shock.

PMID- 15721858
TI  - Emerging evidence for the role of cardiotrophin-1 in cardiac repair in the
      infarcted heart.
AB  - Ischemic heart disease is the most common cause of mortality worldwide. Cardiac
      fibroblasts and myofibroblasts, i.e., the hypersecretory, muscular, and
      contractile fibroblastic phenotype variant, play an important role in myocardial
      healing and are responsible for accumulation of collagen in the infarct scar as
      well as in viable myocardium. Thus, cardiac fibroblasts and myofibroblasts
      directly contribute to cardiac stiffness, altered performance, and ultimately to
      the onset of systolic and diastolic heart failure. Cardiotrophin-1 (CT-1) is a
      member of the IL-6 superfamily and is elevated in the serum of patients with
      ischemic heart disease and valvular heart disease; it is also known to induce
      cardiomyocyte hypertrophy in vitro. The recent, burgeoning awareness of the
      functions of IL-6 superfamily of cytokines within cardiovascular diseases
      predicates this summary of CT-1's effect in cardiac wound healing, and
      particularly after the induction of myocardial infarction. Further, we summarize
      recent results of cardiac CT-1 expression post-myocardial infarction (post-MI) as
      well as the effect of CT-1 on cultured primary adult rat cardiac fibroblasts with
      respect to proliferation and collagen secretion. It would appear that CT-1 plays
      an important and heretofore largely unrecognized role in infarct scar formation
      and angiogenesis in the rat model of chronic MI. Further work is required to
      determine factors that induce CT-1 expression, its interplay with other mediators
      of cardiac infarct wound healing in the setting of acute cardiac ischemia and
      chronic post-MI heart failure, and ultimately whether it confers a beneficial
      effect or contributes to maladaptive cardiac fibrosis.

PMID- 15721859
TI  - Annexins and Ca2+ handling in the heart.
AB  - Annexins are a family of 13 proteins known to bind phospholipids (PL) in a Ca(2+)
      dependent way. They are ubiquitous proteins and share a similar structure
      characterized by a conserved C-terminal domain with Ca(2+) binding sites and a
      variable N-terminal domain. Depending on Ca(2+) concentration, they have been
      reported to participate in a variety of membrane-related events such as
      exocytosis, endocytosis, apoptosis and binding to cytoskeletal proteins. They
      have also been reported to regulate protein activities. This review will focus on
      annexins in the heart, and particularly on annexins A2, A5, A6 and A7. Annexin A2
      has been found in endothelial cells and reported to play a central role in
      control of plasmin-mediated processes. Annexin A5 is mainly localized in
      cardiomyocytes. However, it could be relocated to interstitial tissue in ischemic
      and failing hearts or it could be externalized and exhibit a proapoptotic effect
      in cardiomyocytes. Annexin A6 is the most abundant annexin in the heart, and has
      been localized in various cell types including myocytes. Overexpression of
      annexin A6 has underlined physiological alterations in contractile mechanics
      leading to dilated cardiomyopathy, whereas knockout has been found to induce
      faster changes in Ca(2+) transient and increased contractility, suggesting a
      negative inotropic role for annexin A6. Annexin A7 is expressed in heart and
      skeletal muscle. In annexin A7 null mutant mice decreases in the force-frequency
      relationship were observed in adult cardiomyocytes, consistent with regulation of
      Ca(2+) handling. In conclusion, while annexin A2 was involved in regulation of
      fibrin homeostasis, alterations in expression and activity of annexins A5, A6 and
      A7 have been associated with regulation of Ca(2+) handling in the heart, but the
      target of each annexin has not yet been identified.

PMID- 15721860
TI  - Adenosine produces nitric oxide and prevents mitochondrial oxidant damage in rat
      cardiomyocytes.
AB  - OBJECTIVE: To examine if adenosine prevents oxidant-induced mitochondrial
      dysfunction by producing nitric oxide (NO) in cardiomyocytes. METHODS AND
      RESULTS: Adenosine significantly enhanced the fluorescence of DAF-FM, a dye
      specific for NO, implying that adenosine induces synthesis of NO. Adenosine
      induced NO production was blocked by both the nonspecific NOS inhibitor N(G)
      nitro-l-arginine methyl ester (l-NAME) and N(5)-(1-Iminoethyl)-l-ornithine
      dihydrochloride (l-NIO), an inhibitor of endothelial NOS (eNOS), but not by N(6)
      (1-Iminoethyl)-l-lysine hydrochloride (l-NIL), an inhibitor of inducible NOS
      (iNOS), indicating that adenosine activates eNOS. Adenosine also enhances eNOS
      phosphorylation and its activity. The adenosine A(2) receptor antagonist 8-(3
      chlorostyryl)caffeine but not the A(1) antagonist 8-cyclopentyl-1,3
      dipropylxanthine prevented the increase in NO production. CGS21680, an adenosine
      A(2) receptor agonist, markedly increased NO, further supporting the involvement
      of A(2) receptors. Adenosine-induced NO production was blocked by 4-Amino-5-(4
      chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine (PP2), a selective Src
      tyrosine kinase inhibitor, suggesting that Src tyrosine kinase is crucial for
      adenosine-induced NO production. Adenosine-induced NO production was partially
      reversed by both wortmannin and Akt inhibitor indicating an involvement of PI3
      kinase/Akt. Pretreatment of cells with adenosine prevented H(2)O(2)-induced
      depolarization of mitochondrial membrane potential (DeltaPsi(m)). The protective
      effect was blocked by l-NAME and l-NIO but not by l-NIL, indicating that eNOS
      plays a role in the action of adenosine. The protective effect of adenosine was
      further suppressed by KT5823, a specific inhibitor of protein kinase G (PKG),
      indicating the PKG may serve as a downstream target of adenosine. CONCLUSION:
      Adenosine protects mitochondria from oxidant damage through a pathway involving
      A(2) receptors, eNOS, NO, PI3-kinase/Akt, and Src tyrosine kinase.

PMID- 15721861
TI  - alpha8beta1 Integrin expression in the rat carotid artery: involvement in smooth
      muscle cell migration and neointima formation.
AB  - OBJECTIVE: Migration of vascular smooth muscle cells (VSMCs) from the tunica
      media to the intima is a key event in neointima formation after coronary artery
      angioplasty. The central dogma in VSMC migration is cell modulation from the
      contractile to the noncontractile phenotype. Increased alpha8beta1 integrin
      expression, observed in situations where the majority of cells are in the
      contractile phenotype, led us to hypothesize that a decrease of alpha8beta1
      integrin may play an important role in the migratory state of VSMCs. METHODS AND
      RESULTS: To test this hypothesis, neointima formation was induced in the left
      common carotid artery of adult male Sprague-Dawley rats by balloon dilatation.
      Immunohistochemical and Western blotting analysis showed reduced expression for
      up to 4 weeks of both the alpha8 and beta1 integrin subunits as well as smooth
      muscle alpha-actin in the tunica media following balloon injury. Moreover, ex
      vivo culture of carotid VSMCs revealed diminished alpha8 integrin expression in
      the platelet-derived growth-factor-dependent migratory state with an increase in
      the angiotensin-II-induced contractile state. To ascertain the functional role of
      alpha8 integrin in VSMC migration and proliferation, alpha8 gene expression was
      reduced by nearly 70% by short interference RNA (siRNA). Decreased alpha8
      expression resulted in a significant increase of carotid VSMC migration but not
      of proliferation. CONCLUSIONS: Our results are consistent with those of other
      studies demonstrating that alpha8 integrin could be used as an appropriate
      differentiation marker. In addition, depressed alpha8 integrin expression (after
      vascular injury or siRNA knockdown) was correlated with heightened cell migratory
      activity, demonstrating its potential role in neointima formation.

PMID- 15721863
TI  - Peroxisome proliferator-activated receptor beta/delta activation inhibits
      hypertrophy in neonatal rat cardiomyocytes.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta)
      is the predominant PPAR subtype in cardiac cells and plays a prominent role in
      the regulation of cardiac lipid metabolism. However, the role of PPARbeta/delta
      activators in cardiac hypertrophy is not yet known. METHODS AND RESULTS: In
      cultured neonatal rat cardiomyocytes, the selective PPARbeta/delta activator L
      165041 (10 micromol/L) inhibited phenylephrine (PE)-induced protein synthesis
      ([(3)H]leucine uptake), induction of the fetal-type gene atrial natriuretic
      factor (ANF) and cardiac myocyte size. Induction of cardiac hypertrophy by PE
      stimulation also led to a reduction in the transcript levels of both muscle-type
      carnitine palmitoyltransferase (50%, P<0.05) and pyruvatedehydrogenase kinase 4
      (30%, P<0.05), and these changes were reversed in the presence of the
      PPARbeta/delta agonist L-165041. Stimulation of neonatal rat cardiomyocytes with
      PE and embryonic rat heart-derived H9c2 cells with lipopolysaccharide (LPS)
      enhanced the expression of the nuclear factor (NF)-kappaB-target gene monocyte
      chemoattractant protein 1 (MCP-1). The induction of MCP-1 was reduced in the
      presence of L-165041, suggesting that this compound prevented NF-kappaB
      activation. Electrophoretic mobility shift assay (EMSA) revealed that L-165041
      significantly decreased LPS-stimulated NF-kappaB binding activity in H9c2
      myotubes. Finally, coimmunoprecipitation studies showed that L-165041 strongly
      enhanced the physical interaction between PPARbeta/delta and the p65 subunit of
      NF-kappaB, suggesting that increased association between these two proteins is
      the mechanism responsible for antagonizing NF-kappaB activation by PPARbeta/delta
      activators. CONCLUSION: These results suggest that PPARbeta/delta activation
      inhibits PE-induced cardiac hypertrophy and LPS-induced NF-kappaB activation.

PMID- 15721862
TI  - Augmented BH4 by gene transfer restores nitric oxide synthase function in
      hyperglycemic human endothelial cells.
AB  - OBJECTIVE: Endothelial dysfunction in diabetes is characterized by decreased
      nitric oxide (NO) bioactivity and increased superoxide (SO) production. Reduced
      levels of tetrahydrobiopterin (BH4), an essential cofactor of endothelial NO
      synthase (eNOS), appear to be associated with eNOS enzymatic uncoupling. We
      sought to investigate whether augmented BH4 biosynthesis in hyperglycemic human
      aortic endothelial cells (HAEC) by adenovirus-mediated gene transfer of GTP
      cyclohydrolase I (GTPCH, the rate-limiting enzyme for the de novo BH4 synthesis),
      would be sufficient to rescue eNOS activity and dimerization. HAEC were cultured
      in media with low glucose (5 mM) or high glucose (30 mM). METHODS: After 5 days,
      the cells with/without GTPCH gene transfer (AdeGFP as a control) were prepared
      for assays of (1) NO with electron paramagnetic resonance (EPR); (2) SO with
      cytochrome c reduction and dihydroethidine (DHE) fluorescence; (3) BH4 with high
      performance liquid chromatography (HPLC); (4) eNOS expression and dimerization
      with immunoblotting. RESULTS: We found that high glucose decreased HAEC NO and
      increased SO production, in association with reductions in both total biopterin
      and BH4 levels. High glucose increased total eNOS protein levels in HAEC 1.5
      fold, but this was present principally in the monomeric form. GTPCH gene transfer
      increased cellular biopterin levels and NO production but decreased SO
      production. Furthermore, augmenting BH4 increased the eNOS dimer:monomer ratio
      2.6-fold. CONCLUSION: This study demonstrates a critical role for BH4 in
      regulating eNOS function, suggesting that GTPCH is a rational target to augment
      endothelial BH4 and recover eNOS activity in hyperglycemic endothelial
      dysfunction states.

PMID- 15721864
TI  - Temporal and spatial expression pattern of beta1 sodium channel subunit during
      heart development.
AB  - OBJECTIVES: The aim of this study is to analyze Scn1b mRNA expression levels and
      protein distribution of Scn1b, a putative modulator of the pore-forming Na(+)
      channel subunit in the heart, during mouse cardiac development. METHODS: Scn1b
      mRNA levels were determined by real-time RT-PCR using embryonic hearts ranging
      from E9.5 to E18.5 as well as in postnatal and adult heart. Scn1b protein
      distribution and subcellular localization during cardiogenesis were analyzed by
      immunohistochemistry and confocal microscopy. RESULTS: Scn1b mRNA showed a
      dynamic expression pattern, peaking at stage E12.5 and decreasing at E15.5. Scn1b
      mRNA increased at later embryonic and neonatal stages, being maximal in the adult
      heart. Immunohistochemistry experiments revealed comparable distribution of Scn1b
      protein between the different cardiac chambers at early embryonic stages. With
      further development, Scn1b protein showed an enhanced expression in the
      trabeculated myocardium and the bundle branches. At the subcellular level in
      later embryonic and postnatal mouse cardiomyocytes, Scn1b was present in T
      tubules as identified by immunostaining of alpha-actinin, and in the intercalated
      disks as identified by immunostaining of connexin 43. CONCLUSION: These results
      demonstrate that Scn1b is expressed during mouse heart development, suggesting it
      can play an important role in the action potential configuration of the
      cardiomyocytes during heart morphogenesis.

PMID- 15721865
TI  - Apico-basal inhomogeneity in distribution of ion channels in canine and human
      ventricular myocardium.
AB  - OBJECTIVES: The aim of the present study was to compare the apico-basal
      distribution of ion currents and the underlying ion channel proteins in canine
      and human ventricular myocardium. METHODS: Ion currents and action potentials
      were recorded in canine cardiomyocytes, isolated from both apical and basal
      regions of the heart, using whole-cell voltage clamp techniques. Density of
      channel proteins in canine and human ventricular myocardium was determined by
      Western blotting. RESULTS: Action potential duration was shorter and the
      magnitude of phase-1 repolarization was significantly higher in apical than basal
      canine myocytes. No differences were observed in other parameters of the action
      potential or cell capacitance. Amplitude of the transient outward K(+) current
      (29.6+/-5.7 versus 16.5+/-4.4 pA/pF at +65 mV) and the slow component of the
      delayed rectifier K(+) current (5.61+/-0.43 versus 2.14+/-0.18 pA/pF at +50 mV)
      were significantly larger in apical than in basal myocytes. Densities of the
      inward rectifier K(+) current, rapid delayed rectifier K(+) current, and L-type
      Ca(2+) current were similar in myocytes of apical and basal origin. Apico-basal
      differences were found in the expression of only those channel proteins which are
      involved in mediation of the transient outward K(+) current and the slow delayed
      rectifier K(+) current: expression of Kv1.4, KChIP2, KvLQT1 and MinK was
      significantly higher in apical than in basal myocardium in both canine and human
      hearts. CONCLUSIONS: The results suggest that marked apico-basal electrical
      inhomogeneity exists in the canine-and probably in the human-ventricular
      myocardium, which may result in increased dispersion, and therefore, cannot be
      ignored when interpreting ECG recordings, pathological alterations, or drug
      effects.

PMID- 15721866
TI  - Effects of neonatal hypoxia in the rat on inotropic stimulation of the adult
      heart.
AB  - OBJECTIVE: To determine whether transient hypoxia in neonatal rats has long
      lasting effects on inotropic stimulation of the adult heart. METHODS: The hearts
      of adult male Sprague-Dawley rats (89+/-1 (S.E.M.) days, 432+/-5 g) were studied.
      Half the animals had been subjected to neonatal hypoxia (FiO(2)=0.12, days 1-10)
      while the others had not. The peak response of left ventricular pressure (LVP)
      and the maximum rate of pressure increase (+dP/dtmax) were measured in isolated
      and perfused hearts during application of dobutamine, isoproterenol, milrinone
      and betaxolol. Left ventricular myocyte membranes were analyzed for beta receptor
      density, adenylyl cyclase activity and content. RESULTS: LVP and +dP/dtmax
      responses to stimulation with dobutamine and isoproterenol were significantly
      impaired in adult hearts of neonatally hypoxic rats. The inotropic effect of
      dobutamine was abolished by blockade with the beta(1)-selective antagonist
      betaxolol. The inotropic effects of the phosphodiesterase inhibitor milrinone
      were also significantly decreased in neonatally hypoxic adult hearts. There was
      no difference in left ventricular myocyte membrane beta receptor density of adult
      hearts whether they were hypoxic neonatally or not. However, left ventricular
      adenylyl cyclase activity on isoproterenol or forskolin stimulation and adenylyl
      cyclase levels (type V/VI) were significantly reduced in neonatally hypoxic adult
      hearts. CONCLUSIONS: Neonatal hypoxia in the rat has long-lasting effects on the
      left ventricular response to inotropic stimulation at maturity likely at least in
      part due to diminished left ventricular adenylyl cyclase levels.

PMID- 15721867
TI  - Appearance of a ventricular 5-HT4 receptor-mediated inotropic response to
      serotonin in heart failure.
AB  - BACKGROUND: Current pharmacological treatment of congestive heart failure (CHF)
      addresses changes in neurohumoral stimulation or cardiac responsiveness to such
      stimulation. Yet, undiscovered neurohumoral changes, adaptive or maladaptive, may
      occur in CHF and suggest novel pharmacological treatment. Serotonin [5
      hydroxytryptamine (5-HT)] enhances contractility and causes arrhythmias through 5
      HT(4) receptors in human atrium and ventricle but not through rat ventricular 5
      HT(4) receptors. OBJECTIVE: We investigated whether CHF could induce ventricular
      responsiveness to serotonin. METHODS: Postinfarction CHF was induced in male
      Wistar rats by coronary artery ligation. Contractility was measured in left
      ventricular papillary muscles 6 weeks after infarction. Messenger RNA was
      quantified by RT-PCR and cAMP by RIA. RESULTS: Serotonin caused positive
      inotropic (-logEC(50)=7.5) and lusitropic effects in CHF but not Sham papillary
      muscles. The inotropic effect of 10 muM serotonin in CHF (31.3+/-2.2%) was of
      similar size as the effect of 10 muM isoproterenol (34.0+/-1.7%). The effects of
      serotonin were antagonised by GR113808 (0.5-5 nM), consistent with mediation
      through 5-HT(4) receptors. This was further supported by positive inotropic
      effects of the 5-HT(4)-selective partial agonist RS67506. Carbachol blunted the
      serotonin responses and serotonin increased ventricular and cardiomyocyte cAMP,
      consistent with coupling to G(s) and adenylyl cyclase. Quantitative RT-PCR
      revealed fourfold increased 5-HT(4(b)) mRNA expression in CHF vs. Sham
      ventricles. CONCLUSION: Functional ventricular 5-HT(4) receptors are induced by
      myocardial infarction and CHF of the rat heart. We propose that they are a model
      for ventricular 5-HT(4) receptors of human failing heart and may play a
      pathophysiological role in heart failure.

PMID- 15721868
TI  - Benidipine, a long-acting calcium channel blocker, inhibits cardiac remodeling in
      pressure-overloaded mice.
AB  - OBJECTIVE: The effects of long-acting calcium channel blockers (CCBs) on pressure
      overload-induced cardiac remodeling are seldom studied in animals. We evaluated
      the effects of benidipine, a long-acting CCB, on cardiac remodeling. METHODS: Rat
      neonatal cardiac myocytes were used to examine the influence of benidipine on
      protein synthesis. Cardiac remodeling was induced in C57 B6/J mice by transverse
      aortic constriction (TAC). Then the effects of benidipine (10 mg/kg/d) were
      assessed on myocardial hypertrophy and heart failure, cardiac histology, and gene
      expression. RESULTS: Benidipine significantly inhibited protein synthesis by
      cardiac myocytes stimulated with phenylephrine (PE), and this effect was
      partially abolished by cotreatment with a nitric oxide synthase (NOS) inhibitor
      [N(G)-nitro-l-arginine methylester (l-NAME)]. Four weeks after the onset of
      pressure overload, benidipine therapy potently inhibited cardiac hypertrophy and
      prevented heart failure. The heart to body weight ratio was 6.89+/-0.48 mg/g in
      treated mice vs. 8.76+/-0.33 mg/g in untreated mice (P<0.01), and the lung to
      body weight ratio was 7.39+/-0.93 mg/g vs. 10.53+/-0.99 mg/g, respectively
      (P<0.05). Left ventricular fractional shortening (LVFS) was improved on
      echocardiography. Plasma NO levels were increased, while B type natriuretic
      peptide, protein inhibitor of neuronal NOS, and procollagen IV alpha were down
      regulated in benidipine-treated mice. CONCLUSION: These results indicate that
      benidipine inhibits cardiac remodeling due to pressure overload at least partly
      by acting on the nitric oxide signaling pathway.

PMID- 15721869
TI  - Exercise unmasks autonomic dysfunction in swine with a recent myocardial
      infarction.
AB  - OBJECTIVE: Severe congestive heart failure is associated with autonomic imbalance
      consisting of an increased sympathetic and decreased parasympathetic activity. In
      the present study, we investigated the influence of alterations in autonomic
      balance on cardiovascular function in 11 swine with left ventricular (LV)
      dysfunction produced by a 2- to 3-week-old myocardial infarction (MI). METHODS:
      Swine underwent permanent occlusion of the left circumflex coronary artery
      resulting in MI of the lateral LV wall. Autonomic activity was studied 2-3 weeks
      later using blockers of muscarinic (atropine), alpha-adrenergic (phentolamine)
      and beta-adrenergic (propranolol) receptors. RESULTS: Under resting conditions,
      parasympathetic and sympathetic control of the heart and coronary circulation
      were similar in MI and normal swine. In contrast, during exercise of MI compared
      to normal swine, (i) there was a more pronounced gradual inhibition of
      parasympathetic control of heart rate with increasing exercise intensity; (ii)
      circulating catecholamines increased excessively, resulting in an increased beta
      adrenergic influence on heart rate, while (iii) the beta-adrenergic influence on
      global left ventricular contractility was decreased, reflecting a blunted left
      ventricular beta-adrenergic responsiveness. Furthermore, (iv) an alpha-adrenergic
      vasoconstrictor influence was absent in the anterior LV wall of both MI and
      normal swine, while (v) the beta-adrenergic vasodilator influence in the coronary
      circulation was not different between normal and MI swine, which, in conjunction
      with the elevated catecholamine levels during exercise, suggests a diminished
      beta-adrenergic responsiveness of coronary resistance vessels within remote non
      infarcted myocardium in MI swine. CONCLUSIONS: Swine with a recent MI display
      autonomic dysfunction, which is characterized by a more pronounced inhibition of
      parasympathetic influence and an exaggerated increase in sympathetic drive during
      exercise, as well as reduced myocardial and coronary vascular beta-adrenergic
      responsiveness.

PMID- 15721870
TI  - Oxidized low-density lipoprotein increases superoxide production by endothelial
      nitric oxide synthase by inhibiting PKCalpha.
AB  - OBJECTIVE: Oxidized low-density lipoprotein (ox-LDL) increases superoxide anion
      (O(2)(-)) production by the endothelial nitric oxide (NO) synthase (eNOS). We
      assessed whether the uncoupling of eNOS was associated with alterations in eNOS
      phosphorylation and/or the assembly of the eNOS signaling complex. METHODS AND
      RESULTS: In unstimulated human endothelial cells, eNOS Thr(495) was
      constitutively phosphorylated. ox-LDL, but not native LDL, enhanced the
      production of O(2)(-) by endothelial cells, an effect that was partially
      sensitive to NOS inhibition. ox-LDL, but not native LDL, induced a time- and
      concentration-dependent decrease in the phosphorylation of eNOS on Thr(495).
      Protein kinase C (PKC) has been reported to phosphorylate this residue, and the
      increase in the phosphorylation of Thr(495) induced by phorbol 12-myristate 13
      acetate was attenuated in cells pretreated with ox-LDL. Moreover, the
      phosphorylation and activity of PKCalpha was attenuated by ox-LDL and paralleled
      the changes in eNOS phosphorylation. ox-LDL also induced the dissociation of eNOS
      from the plasma and Golgi membranes. In COS-7 cells, a T495A eNOS mutant
      generated significantly more O(2)(-) than a T495D mutant did, indicating that the
      dephosphorylation of Thr(495) alone can increase O(2)(-) production by eNOS.
      However, although the dephosphorylation of Thr(495) in histamine-stimulated
      endothelial cells enhanced the binding of calmodulin to eNOS, calmodulin no
      longer bound to eNOS from ox-LDL-treated endothelial cells. CONCLUSIONS: These
      results indicate that a decrease in the activity of PKCalpha in ox-LDL-treated
      endothelial cells is associated with the dephosphorylation of eNOS, dissociation
      of the eNOS signaling complex, and the enhanced production of eNOS-derived O(2)(
      ).

PMID- 15721871
TI  - The effects of PPAR-gamma ligand pioglitazone on platelet aggregation and
      arterial thrombus formation.
AB  - BACKGROUND: It has been suggested that peroxisome proliferator-activated receptor
      (PPAR)-gamma ligands reduce the development of atherosclerosis and myocardial
      ischemia-reperfusion injury; both of these phenomena are associated with platelet
      activation. We postulated that PPAR-gamma activation would inhibit platelet
      activation and intra-arterial thrombus formation. METHODS AND RESULTS: Sprague
      Dawley rats were fed chow mixed with pioglitazone (1 or 10 mg/kg/day) for 7 to 10
      days. A filter soaked in 30% FeCl(3) was applied around the abdominal aorta to
      study the patterns of arterial thrombogenesis. The aortic blood flow was
      continuously monitored using an ultrasonic Doppler flow probe. ADP and
      arachidonic acid-induced platelet aggregation and the expression of constitutive
      nitric oxide synthase (cNOS) and thrombomodulin in aorta were measured.
      Pioglitazone feeding delayed the time to occlusive thrombus formation by 40%
      (P<0.01 vs. control, n=9) without affecting the weight of the thrombus. ADP- as
      well as arachidonic acid-induced platelet aggregation was also inhibited by
      pioglitazone feeding (P<0.01 vs. control, n=9). Pioglitazone feeding also
      upregulated the aortic expression of cNOS and thrombomodulin; both are considered
      important factors in platelet aggregation and thrombus formation in vivo. The
      effect of a high dose (10 mg/kg/day) of pioglitazone was not more potent than
      that of a low dose (1 mg/kg/day). CONCLUSION: These results indicate that
      pioglitazone administration decreases platelet aggregation and delays intra
      arterial thrombus formation in rats, at least partially, by an increase in the
      expression of cNOS and thrombomodulin.

PMID- 15721872
TI  - Urocortin-induced relaxation in the human internal mammary artery.
AB  - OBJECTIVE: Urocortin, a potent vasodilator, plays physiological or
      pathophysiological roles in the cardiovascular system. However, little is known
      about its action in human vascular tissues. The present study was designed to
      investigate the vascular effect of urocortin on human internal mammary artery
      (IMA) in vitro and the possible underlying mechanisms. METHODS: Human IMA was
      obtained from patients undergoing coronary artery bypass grafting. The isolated
      IMA rings were mounted in organ baths and changes in isometric tension were
      measured by using Grass force-displacement transducer. Corticortropin-releasing
      factor-receptors (CRF-R) were also analyzed in the IMA by using RT-PCR analysis.
      RESULTS: In 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha)
      (U46619)-precontracted endothelium-intact rings, urocortin induced concentration
      dependent relaxations with pD(2) of 8.69+/-0.11 and this effect was markedly
      reduced in endothelium-denuded rings. Relaxations to urocortin in endothelium
      intact rings were attenuated to the same extent after treatment with N(G)-nitro-l
      arginine (l-NNA) and 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ). Urocortin
      induced relaxations were also inhibited by treatment with putative K(+) channel
      blockers, such as tetraethylammonium (TEA(+)), charybdotoxin (CTX), and
      iberiotoxin (IBX). In endothelium-denuded rings, treatment with TEA(+), CTX, or
      IBX attenuated relaxation to urocortin as well as sodium nitroprusside (SNP). The
      bands for CRF-R1, CRF-R2alpha, and CRF-R2beta mRNAs were observed in both
      endothelium-intact and endothelium-denuded human IMA. CONCLUSION: Urocortin
      produced both endothelium-dependent and -independent relaxation in human IMA
      rings. The endothelium-dependent component primarily involves the release of
      endothelial nitric oxide (NO) that in turn stimulates Ca(2+)-activated K(+)
      channels in vascular smooth muscle via cyclic GMP-dependent mechanisms. CRF-R1,
      CRF-R2alpha, and CRF-R2beta mRNAs are present in the human IMA.

PMID- 15721873
TI  - Antifibrotic effect of adrenomedullin on coronary adventitia in angiotensin II
      induced hypertensive rats.
AB  - OBJECTIVE: The extracellular matrix (ECM) determines the structural integrity of
      the heart and vasculature, participating in cardiovascular remodeling. We
      previously reported that adrenomedullin (AM) inhibited cellular proliferation and
      protein synthesis of cardiac fibroblasts; however, the precise mechanisms of AM
      actions as an antifibrotic factor remain unknown. The purpose of this study was
      to examine the biological actions of AM against the profibrotic factor
      angiotensin II (Ang II) in coronary adventitia. METHODS AND RESULTS: Rats with
      hypertension induced by Ang II infusion were administered 0.06 mug/kg/min
      recombinant human AM subcutaneously for 14 days. The AM infusion significantly
      (p<0.05) reduced the Ang II-induced increase of coronary adventitial fibroblasts
      expressing Ki-67 and alpha-smooth muscle actin (alpha-SMA) in the left ventricle,
      by 65%, and 62%, respectively, without affecting systolic blood pressure, left
      ventricle/body weight, or cross-sectional area of myocardial fibers. Collagen
      deposition of coronary arteries was reduced by the AM infusion (-24%, p<0.01),
      and these effects of AM were accompanied by significant reductions in gene
      expression of type 1 collagen (-49%, p<0.05) and transforming growth factor-beta1
      (TGF-beta1) (-55%, p<0.01). In cultured cardiac fibroblasts, 10(-7) mol/L AM
      exerted an inhibitory effect on TGF-beta1-induced alpha-SMA expression (p<0.01)
      that was mimicked by 8-bromo-cAMP and attenuated by the protein kinase A
      inhibitor H-89. CONCLUSION: AM decreased Ang II-induced collagen deposition
      surrounding the coronary arteries, inhibiting myofibroblast differentiation and
      expressions of ECM-related genes in rats. The present findings further support
      the biological action of AM as an antifibrotic factor in vascular remodeling.

PMID- 15721875
TI  - What is a monophasic action potential recorded by the Franz contact electrode?

PMID- 15721874
TI  - Functional interaction between nucleus tractus solitarius NK1 and 5-HT3 receptors
      in the inhibition of baroreflex in rats.
AB  - OBJECTIVE: Previous data showed that in the nucleus tractus solitarius (NTS), 5
      HT(3) receptors are critically involved in the inhibition of cardiac baroreceptor
      reflex response occurring during the defense reaction. Since stimulation of NTS
      NK(1) receptors has been found to inhibit the baroreflex bradycardia, we examined
      in this study whether this reflex response is inhibited during the defense
      reaction via an interaction between NK(1) and 5-HT(3) receptors. METHODS: For
      this purpose, we analyzed in urethane-anaesthetized rats the effects of intra-NTS
      GR205171, a selective NK(1) receptor antagonist, on the baroreflex bradycardia
      inhibition observed either during the defense reaction triggered by electrical
      stimulation of the dorsal periaqueductal grey matter (dPAG) or after NTS 5-HT(3)
      receptor activation. RESULTS: Intra-NTS GR205171, reversed, in dose-dependent
      manner, the inhibitory effect of dPAG stimulation on baroreflex bradycardia. This
      reversion was of 49% when both sinus carotid and aortic baroreceptors were
      stimulated by phenylephrine, and of 84% when aortic depressor nerve was
      stimulated. Similarly, intra-NTS GR205171 reversed partially or almost totally
      the inhibitory effect of local microinjections of phenylbiguanide, a 5-HT(3)
      receptor agonist, on baroreflex bradycardia induced either by phenylephrine
      administration or aortic nerve stimulation, respectively. CONCLUSION: These
      results strongly suggest that NK(1) receptors contribute downstream to the 5
      HT(3) receptor-mediated inhibition of the aortic but not carotid cardiac
      baroreflex response occurring during the defense reaction, therefore implying
      that baroreceptor afferent inputs may be differentially modulated depending on
      their origin. This differentiation may be useful for a better understanding of
      baroreflex dysfunction in disease-induced conditions.

PMID- 15721877
TI  - Diesel emissions significantly influence composition and mutagenicity of ambient
      particles: a case study in Sao Paulo, Brazil.
AB  - In 2003, a bus strike paralyzed the fleet of buses in Sao Paulo, Brazil during 3
      days, from 6 to 8 of April, the complete interruption of services being achieved
      on the 7th. We evaluated the effect of the absence of this source of pollution on
      the composition, mutagenicity, and toxicity of the fine particulate material
      collected during this period. Particles were sampled in glass fiber filters on
      days 7 and 15 of April of 2003 (strike and nonstrike days, respectively), using a
      high-volume sampler. Trace element determinations (As, Br, Co, Cl, Fe, La, Mn,
      Sb, Sc, and Th) of particulate material samples were carried out by neutron
      activation analysis. Sulfur determination was done by X-ray fluorescence
      analysis. The ratio between nonstrike/strike concentrations of hydrocarbons
      associated with automotive emissions (benzene, toluene, ethyl-benzene, and
      xylenes; BTEX) was determined by gas chromatography/mass spectrometry.
      Mutagenesis of testing solutions was determined by means of the Tradescantia
      micronucleus assay in early tetrads of Tradescantia pallida. The inhibition of
      mitosis of the cells of the primary meristema of the root tips of Allium cepa was
      used as an index of the toxicity. Fine particle trace element contents were lower
      during the strike. The concentrations of sulfur and BTEX were 50% and 39.3%
      lower, respectively, on the strike day. A significant (P=0.038) reduction of
      micronuclei induced by fine particles sampled during the strike was observed. No
      effect of the strike on toxicity was detected. These results indicate that a
      program aiming to reduce emissions of the bus fleet in our town may impact
      positively the air quality by reducing the mutagenic potential of ambient
      particles.

PMID- 15721878
TI  - Breastfeeding and concentrations of HCB and p,p'-DDE at the age of 1 year.
AB  - Exposure to organochlorine compounds (OCs) occurs both in utero and through
      breastfeeding. Levels of hexachlorobenzene (HCB) in the cord serum of newborns
      from a population located in the vicinity of an electrochemical factory in Spain
      are among the highest ever reported. We aimed to assess the degree of breast milk
      contamination in this population and the subsequent exposure of children to these
      chemicals through breastfeeding. A birth cohort including 92 mother-infant pairs
      (84% of all births in the study area) was recruited between 1997 and 1999 in five
      neighboring villages. OCs were measured in cord serum, colostrum, breast milk,
      and children's serum at 13 months of age. Concentrations of OCs were detected and
      quantified in all colostrum and milk samples. The concentrations in mature milk
      were lower than those encountered in colostrum. At 13 months of age the highest
      concentration of OC was found for dichlorodiphenyl dichloroethane (p,p'-DDE), in
      contrast to what these children presented at birth, where HCB was the highest
      compound. Those infants who were breastfed had higher concentrations at the age
      of 1 than those who were formula fed (2.13 ng/mL of HCB among formula feeders vs
      4.26 among breast feeders, and 1.95 of p,p'-DDE vs 6.00 (P<0.05)). Long-term
      breastfeeding leads to a dose-response increase of the concentrations in
      children's serum during the first year of life.

PMID- 15721879
TI  - Mercury exposure in two coastal communities of the Bay of Fundy, Canada.
AB  - There is a rising global concern with regard to mercury (Hg) exposure among
      coastal populations. Two communities on the Bay of Fundy (New Brunswick, Canada)
      were assessed by hair monitoring and dietary methods. Average concentration of
      total Hg in hair was 0.70+/-0.55 mg/kg (N=91) at Grand Manan and 0.42+/-0.15
      mg/kg (N=52) at St. Andrews/St. Stephen. Average daily consumption of fresh fish
      and shellfish was 50+/-40 g/day for Grand Manan and 19+/-19 g/day for St.
      Andrews/St. Stephen. Average daily total Hg intake estimated from the food
      frequency and 24-h recall questionnaires was 0.05+/-0.04 microg Hg/kg bw/day at
      Grand Manan and 0.03+/-0.04 microg Hg/kg bw/day at St. Andrews/St. Stephen. A
      significant correlation (r=0.47, P=0.002) between Hg intake and hair was observed
      for Grand Manan. Low Hg intakes and body burden can be attributed to the low Hg
      levels found in the species commonly consumed: haddock, canned tuna, lobster, and
      pollock (all below 0.2 microg/g wet weight). The results showed that Hg exposure
      in these Canadian coastal communities is low; fish with higher levels of Hg
      (shark, tuna, swordfish, pickerel, and bass) are not consumed locally.

PMID- 15721880
TI  - Intestinal metabolism of PAH: in vitro demonstration and study of its impact on
      PAH transfer through the intestinal epithelium.
AB  - Food would seem to be one of the main ways of animal and human contamination with
      polycyclic aromatic hydrocarbons (PAHs). In vivo studies suggest a transfer in
      intestinal epithelium by diffusion, which appears extensively governed by the
      physicochemical properties of PAHs, particularly lipophilicity. However, other
      mechanisms, such as metabolism, are considered to intervene. Our work aimed at
      testing in vitro intestinal metabolism and defining its impact on transepithelial
      transport of PAHs. Caco-2 cells were cultivated on permeable filters and
      incubated with 14C-labeled benzo[a]pyrene (BaP), pyrene (Pyr), and phenanthrene
      (Phe), which differ in their physicochemical properties. The results showed that
      the cells were able to metabolize the compounds. In basal media, Phe appeared to
      be the least hydroxylated molecule (45% after a 6-h exposure), followed by Pyr
      (65%) and finally BaP (96%). Inhibition of PAH metabolism showed a determinant
      effect on kinetics profiles. Transfer in the basal compartment of BaP, Pyr, and
      Phe radioactivities was, respectively, 26, 4, and 2 times lower with inhibitors,
      corroborating that intestinal metabolism of PAHs would have a positive impact on
      their transfer, an impact that increased with their lipophilicity. Furthermore,
      after a 6-h incubation, metabolites were also detected in apical medium. These
      findings suggested that intestinal metabolism might play a key role in intestinal
      barrier permeability and thus in the bioavailability of tested micropollutants.

PMID- 15721881
TI  - Lead-induced dysregulation of superoxide dismutases, catalase, glutathione
      peroxidase, and guanylate cyclase.
AB  - Previous studies from this laboratory have demonstrated the presence of oxidative
      stress and its role in the pathogenesis of lead-induced hypertension. This study
      was designed to determine whether oxidative stress in animals with lead-induced
      hypertension is associated with dysregulation of the activities of the main
      antioxidant enzymes, namely superoxide dismutase (SOD), catalase (CAT), and
      glutathione peroxidase (GPX). In addition, we aimed to determine the effect of
      lead on the regulation of guanylate cyclase (GC) expression. Male Sprague-Dawley
      rats were randomly assigned to control and lead-exposed groups, and
      immunodetectable Cu/Zn SOD, Mn SOD, CAT, and GPX were determined by
      immunoblotting in the thoracic aorta. Additionally, the activities of these
      enzymes were measured in the renal cortex, medulla, and thoracic aorta.
      Furthermore, immunodetectable GC was determined in the thoracic aorta. In the
      thoracic aorta, lead exposure resulted in significant upregulation of aortic
      Cu/Zn SOD activity, while CAT and GPX activity and CuZn SOD, Mn SOD, and CAT
      protein abundance were unchanged. Conversely, GC protein abundance was decreased
      in thoracic aorta. In renal cortex and medulla, CAT and Cu/Zn SOD activities were
      increased, while GPX activity was unchanged. Lead-exposed animals exhibited
      upregulation of some antioxidant enzyme activities, most likely as a compensatory
      response to lead exposure. However, other enzymes did not compensate in the face
      of oxidative stress, suggestive of an antioxidant/oxidant imbalance. These
      findings, combined with decrease in aortic GC protein abundance, provide further
      evidence for dysregulation of antioxidant/oxidant balance and hypertension in
      this model.

PMID- 15721882
TI  - Uterotrophic effects of benzophenone derivatives and a p-hydroxybenzoate used in
      ultraviolet screens.
AB  - Ultraviolet (UV) sunscreen products are popular because of concerns about UV
      radiation and skin cancer. Unfortunately, some of these products contain agents
      with estrogenic activity. We used an ovariectomized rat uterotrophic assay to
      measure the estrogenic activities of 2,4-dihydroxybenzophenone (2,4-DHBP),
      2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'-THBP), and 4-hydroxybenzoic acid
      isobutyl ester (isobutyl-paraben), which are agents in UV sunscreens, and ethynyl
      estradiol (EE) and bisphenol A (BPA), which are positive controls. All chemicals
      increased rat uterine weights. The 10% effective doses (ED10, mg/kg/day) of EE,
      BPA, 2,4-DHBP, 2,2',4,4'-THBP, and isobutyl-paraben, as determined by Hill
      equation analysis, where 5E-5, 41.1, 544.6, 33.0, and 230.9, respectively, and
      their relative potencies against EE were about 1/800,000, 1/10,000,000,
      1/600,000, and 1/4,000,000, respectively. Our findings indicated that UV screens
      contain weak estrogenic compounds.

PMID- 15721883
TI  - Organic and inorganic forms of selenium inhibited differently fish (Rhamdia
      quelen) and rat (Rattus norvergicus albinus) delta-aminolevulinate dehydratase.
AB  - Selenium contamination in the aquatic environment can produce severe toxic
      effects to fish. The mammalian sulfhydryl-containing enzyme, delta
      aminolevulinate dehydratase (delta-ALA-D), is inhibited after exposure to organic
      and inorganic forms of selenium. In the present study, the inhibitory effect of
      (PhSe)2, (BuSe)2, and Na2SeO3 on the activity of fish hepatic and gill delta-ALA
      D was investigated and compared with the rat liver enzyme. Results indicated that
      delta-ALA-D activity varied considerably depending on the tissue, selenium form,
      and species considered. For fish (liver and gill), the IC50 values for delta-ALA
      D inhibition by (PhSe)2, (BuSe)2, and Na2SeO3 were 274 and 76, 985 and 693, and
      386 and 902 microM, respectively. For rat liver these values were 7, 10, and 5
      microM, respectively. In contrast, fish and rat subcellular fractions similarly
      increased the oxidative effect of (PhSe)2 toward sulfhydryl groups from DTT.
      These catalytic properties of subcellular fractions from fish and rat liver were
      abolished by heat treatment. Taking into account that aquatic organisms can be in
      contact with higher concentrations of selenium for longer periods of time and
      accumulate more selenium than terrestrial animals, it is reasonable to suppose
      that fish delta-ALA-D can be a potential target for organic and inorganic
      selenium forms present in aquatic contaminated environments. From an
      ecotoxicological point of view, our results suggest a link between selenium
      induced anemia signs in fish and the sensitivity of fish delta-ALA-D to selenium
      in natural habitats.

PMID- 15721884
TI  - Is there a linkage between bioaccumulation and the effects of alkylphenols on
      male breams (Abramis brama)?
AB  - There was some evidence from a previous study that estrogenic disruptors, like
      alkylphenols, could effect fish in the small River Saar of Southwestern Germany.
      Concentrations of 4NP and 4NP1EO found in breams (Abramis brama) in the Saar
      River were much higher than those found in other sampling sites of the German
      Environmental Specimen Bank, including those from sampling sites in the Rivers
      Elbe, Rhine, Mulde, and Saale and in Lake Belau. We studied the relationship
      between accumulation and effect using vitellogenin (vtg) and a hepatosomatic
      index (HSI) of estrogenic effects and by measuring concentrations of AP and APE
      accumulated in breams caught at six sampling sites in the River Saar and one in
      the River Mosel. To link these results with those of the previous study we
      standardized our sampling efforts to obtain comparable data. Elevated vtg levels
      were found in the breams at all sampling sites near to or downstream of sewage
      plant discharges, whereas low vtg levels corresponded to sampling sites not
      influenced by municipal waste water. While HSI values did not correspond to the
      location of sampling sites, there was a weak but statistically significant
      correlation to vtg concentrations. Concentrations of four AP and APE were much
      more lower, as in the previous study, and were neither linked with sewage
      treatment plant discharges nor correlated with vtg levels. In conclusion, a
      linkage between accumulation and the effects of AP and APE could not be
      established, but the relationship between elevated vtg concentrations and
      municipal waste water, which contains other important endocrine disruptors, was
      clear.

PMID- 15721885
TI  - Dietary exposure to Aroclor 1254 alters gene expression in Xenopus laevis frogs.
AB  - Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that
      contribute to worldwide health problems. Despite data associating PCBs with
      adverse health effects, decisions to clean up contaminated sites remain
      controversial. Cleanup decisions are typically based on risk assessment methods
      that are not sensitive enough to detect subtle changes in health. We have
      recently shown that gene expression signatures can serve as sensitive molecular
      biomarkers of exposure and related health effects. Our initial studies were
      carried out with developing Xenopus laevis tadpoles that were exposed to the PCB
      mixture Aroclor 1254 (A1254) for 2 days. A1254 was dissolved in dimethyl
      sulfoxide and added to the aquarium water for rapid loading of PCBs into the
      tadpole tissue. These studies showed that increases in the expression of specific
      genes occurred independent of adverse health effects, and decreases in specific
      genes correlated with the appearance of observable health effects, including
      decreased survival and gross morphological and behavioral abnormalities. In this
      report, we extend our previous work to test the use of gene expression signatures
      as biomarkers in frogs exposed to PCBs through the diet from early tadpole stages
      through metamorphosis. This work showed that chronic low-dose exposure to A1254
      (24 ppm) in food produced tissue levels of 17 ppm and increased gene expression
      of nerve growth factor and proopiomelanocortin independent of adverse health
      effects. Exposure to higher doses of A1254 (200 ppm) produced tissue levels of 80
      ppm and increased expression of p450 1A1, also, independent of adverse health
      effects. This work provides further evidence for the use of gene expression
      changes as biomarkers of exposure to PCBs.

PMID- 15721886
TI  - Fish growth rates modulate mercury concentrations in walleye (Sander vitreus)
      from eastern Canadian lakes.
AB  - The majority of the studies attempting to explain fluctuations of mercury (Hg)
      concentrations in fish from diverse aquatic ecosystems have invoked the influence
      of physico-chemical or environmental factors but has eluded that of strictly
      biological factors. In this study, we examine the relationship between Hg
      concentrations in walleye (Sander vitreus) muscles and their growth rates in 12
      natural lakes located in four different regions of Quebec (Saint Lawrence Valley,
      Chibougamau, Abitibi, and Temiscamingue). Hg concentrations vs. total lengths of
      fish were described using polynomial regressions while growth rates (lengths vs.
      ages) were estimated using the Von Bertalanffy growth model. No significant
      differences for fish growth rates or for the relation fish length vs. fish Hg
      concentrations were found among the different regions except for the three lakes
      of the Abitibi region where fish grow more slowly than in the other lakes. Major
      differences were observed for growth rates or lengths vs. Hg concentrations in
      the different walleye populations of each lake. For example, a 5-year-old walleye
      with the lowest growth rate will reach an average length of 325 mm, whereas the
      average length for a walleye with the highest growth rate is 550 mm. Predicted
      values of Hg concentrations in walleyes of a standardized length of 350 mm ranged
      from 0.17 to 0.79 ppm. When all walleye populations of the 12 lakes were
      considered together, growth rates were significantly correlated to Hg
      concentrations (r=0.9244; P<0.001). This suggests that faster-growing walleyes
      will have lower Hg concentrations than slower-growing fish at a given length. The
      growth rate as a biological factor dominates all other environmental factors to
      account for differences in Hg concentrations in walleye populations studied.
      Nevertheless, the minor differences in Hg concentrations observed in walleye
      taken from two separate arms of a single lake in the Temiscamingue region, Lake
      Desjardins, could not be explained by fish growth rates only and thus should be
      related to other environmental parameters.

PMID- 15721887
TI  - The intestinal parasite Pomphorhynchus laevis as a sensitive accumulation
      indicator for the platinum group metals Pt, Pd, and Rh.
AB  - Concentrations of the platinum group elements Pt, Pd, and Rh were analyzed by
      adsorptive cathodic stripping voltammetry (Pt, Rh) and total-reflection X-ray
      fluorescence (Pd) in the intestinal helminth Pomphorhynchus laevis and its host
      Barbus barbus. The fish were caught in the Danube river south of the city of
      Budapest (Hungary) and were exposed to ground catalytic material for 28 days.
      Following exposure all three precious metals were taken up and accumulated in
      host organs and the parasites. Interestingly, in all tissues of the unexposed
      controls Pt was found, whereas Pd was not present in the muscle of the controls
      and Rh was not detectable in muscle and intestine of unexposed barbel. All metals
      were found at significantly higher concentrations in the acanthocephalan than in
      the tissues of barbel. These results are discussed with respect to the
      application of P. laevis as an accumulation indicator for metals.

PMID- 15721888
TI  - Altered exoskeleton composition and vitellogenesis in the crustacean Gammarus sp.
      collected at polluted sites in the Saguenay Fjord, Quebec, Canada.
AB  - Gammarus sp. individuals were collected at four intertidal sites subjected to
      direct sources of pollution (marinas, ferry traffic, and harbors) and at one site
      with no direct source of pollution. Levels of vitellogenin-like proteins (Vtg),
      metallothioneins (MT), alkali-labile phosphates (ALPs) in proteins, and lipogenic
      enzyme activities (i.e., glucose-6-dehydrogenase, isocitrate dehydrogenase, and
      malate enzyme) were measured in whole soft tissues. In exoskeletons, levels of pH
      dependent extractable protein and chitin were determined to assess the possible
      impacts of pollution on exoskeleton integrity and the molting process. Results
      show that males were consistently heavier than females regardless of site quality
      but that the whole-body weight of both sexes was significantly lower at polluted
      sites. Females displayed either induced or decreased Vtg-like proteins at
      polluted sites, indicating significant changes in gametogenesis activity. MT
      levels were not sex dependent and tended to be induced at all impacted sites. ALP
      levels in acetone-fractionated proteins indicate altered phosphate mobilization
      at some impacted sites, where females tended to display higher ALP levels.
      Lipogenic enzyme activities did not vary by sex but were readily increased at
      impacted sites, suggesting a delay in gonad maturation rates. Exoskeleton protein
      characteristics revealed that the proportion of chitin in exoskeletons was a
      lower at most impacted site, suggesting disruption of chitin and pH-dependent
      protein mobilization. Principal component analysis revealed that gammarids
      collected at affected sites displayed substantial changes in the proportion of
      chitin, arthropodin, sclerotin, MTs, and intermediary glucose metabolism (glucose
      6-phosphate dehydrogenase, and isocitrate dehydrogenase in soft tissues) and thus
      suffered from disturbed gametogenesis and exoskeleton integrity.

PMID- 15721889
TI  - Occurrence of antibiotic and metal resistance in bacteria from organs of river
      fish.
AB  - Bacterial populations in some organs, viz., liver, spleen, kidney, gill, and
      arborescent organ of the catfish Clarias batrachus were enumerated followed by
      determination of resistance for antibiotics and metals. The total viable counts
      in these organs, observed, were 2.24x10(4), 2.08x10(4), 1.44x10(4), 1.23x10(4),
      and 6.40x10(3) colony-forming units/mL, respectively. The random bacterial
      isolates from these fish organs showed resistance in decreasing order for
      colistin (98%), ampicillin (82%), gentamycin (34%), carbenicillin (28%),
      tetracyline (20%), streptomycin (12%), and ciprofloxacin (02%). Most of the
      isolates exhibited an increasing order of tolerance for the metals (microg/mL)
      copper (100), lead (200), manganese (400), cadmium (200), and chromium (50), with
      minimum inhibitory concentration (MIC) ranging from <50 to 1600 microg/mL. These
      observations indicate that the significant occurrence of bacterial population in
      organs of fish with high incidence of resistance for antibiotics and metals may
      pose risk to fish fauna and public health.

PMID- 15721891
TI  - Air pollution and hospital admissions for cardiovascular disease in Taipei,
      Taiwan.
AB  - This study was undertaken to determine whether there is an association between
      air pollutants levels and hospital admissions for cardiovascular diseases (CVD)
      in Taipei, Taiwan. Hospital admissions for CVD and ambient air pollution data for
      Taipei were obtained for the period 1997-2001. The relative risk of hospital
      admission was estimated using a case-crossover approach, controlling for weather
      variables, day of the week, seasonality, and long-term time trends. For the one
      pollutant models, on warm days (>or=20 degrees C) statistically significant
      positive associations were found between levels of particulate matter <10-microm
      aerodynamic diameter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), and
      ozone (O3). On cool days (<20 degrees C), all pollutants except O3 and SO2 were
      significantly associated with CVD admissions. For the two-pollutant models, CO,
      NO2, and O3 were significant in combination with each of the other four
      pollutants on warm days. On cool days, PM10 remained statistically significant in
      all the two-pollutant models. This study provides evidence that higher levels of
      ambient pollutants increase the risk of hospital admissions for CVD.

PMID- 15721890
TI  - Comparison of proposed frameworks for grouping polychlorinated biphenyl congener
      data applied to a case-control pilot study of prostate cancer.
AB  - Although the commercial synthesis of polychlorinated biphenyls (PCBs) has been
      banned in the United States for several decades, they are persistent in the
      environment with exposure mainly being through diet. The biologic and toxic
      effects of PCBs and their metabolites are due in part to their ability to
      interact with several cellular and nuclear receptors, thereby altering signaling
      pathways and gene transcription. These effects include endocrine modulation and
      disruption. Therefore, the natural history of cancer in tissues expressing these
      receptors may be modulated by PCB congeners, which are known to have estrogenic,
      antiestrogenic, and other hormonal effects. Several frameworks for grouping PCB
      congeners based on these interactions have been proposed. We conducted a hospital
      based, case-control pilot study of 58 prostate cancer cases and 99 controls to
      evaluate the association between the proposed PCB groupings and the risk of
      prostate cancer. Serum samples were analyzed for a total of 30 PCBs. In
      multivariate analyses, the odds of prostate cancer among men with the highest
      concentrations of moderately chlorinated PCBs or PCBs with phenobarbital-like
      activities (constitutively active receptor (CAR) agonists) was over two times
      that among men with the lowest concentrations. Increasing trends in risk across
      the concentration levels were also observed. These results suggest that a higher
      burden of PCBs that are CAR agonists may be positively associated with an
      increased risk of prostate cancer and they encourage further research in this
      area.

PMID- 15721892
TI  - Reproductive outcomes in DDT applicators.
AB  - OBJECTIVES: To explore reproductive outcomes in relation to occupational exposure
      to DDT. METHODS: We inquired into the reproductive history, including total
      number of children, sex distribution in the offspring, time-to-pregnancy, and
      number of spontaneous abortions and stillbirths, of the spouses of 105 men first
      exposed to DDT in a 1946-1950 anti-malarial campaign in Sardinia, Italy. The time
      to-pregnancy in months at the first successful conception was estimated from
      population Registrars. Cumulative DDT exposure during the anti-malarial campaign
      was retrospectively estimated. RESULTS: The stillbirth rate was elevated and the
      male/female ratio in the offspring was reversed among DDT-exposed workers, and
      particularly among DDT applicators, compared to the unexposed subjects. Among DDT
      applicators, the stillbirth rate increased and the male/female ratio decreased by
      the tertile of cumulative DDT exposure. The fecundity ratio among spouses of DDT
      applicators was 0.72 (95% CI, 0.41,1.21) compared to the unexposed. The average
      number of children and abortion rate were unaffected by DDT exposure.
      CONCLUSIONS: The low statistical power of our study does not allow definitive
      conclusions. However, the results prompt further in-depth research into adverse
      reproductive outcomes and reduced fertility among men heavily exposed to DDT.

PMID- 15721893
TI  - Bladder cancer mortality reduction after installation of a tap-water supply
      system in an arsenious-endemic area in southwestern Taiwan.
AB  - Arsenic has been well documented as the major risk factor for blackfoot disease
      (BFD), a unique peripheral vascular disease that was endemic in the southwestern
      coast of Taiwan, where residents had consumed high-arsenic artesian well water
      for more than 50 years. Long-term arsenic exposure has also been reported to be
      associated with bladder cancer mortality in a dose-response relationship. A tap
      water supply system was implemented in the early 1960s in the BFD endemic areas.
      Artesian well water was no longer used for drinking and cooking after the mid
      1970s. The objective of this study is to examine whether bladder cancer mortality
      decreased after the improvement of the drinking water supply system through
      elimination of arsenic exposure from artesian well water. Standardized mortality
      ratios (SMRs) for bladder cancer were calculated for the BFD endemic area for the
      years 1971-2000. The study results show that mortality from bladder cancer
      declined gradually after the improvement of the drinking water supply system to
      eliminate arsenic exposure from artesian well water. Based on the reversibility
      criterion, this finding strengthened the likelihood of the observed association
      between arsenic exposure and bladder cancer being causal.

PMID- 15721894
TI  - A review of the studies of the cardiovascular health effects of methylmercury
      with consideration of their suitability for risk assessment.
AB  - In the 2000 report of the National Research Council's Committee on the
      Toxicological Effects of Methylmercury (MeHg), various adverse health effects
      potentially associated with MeHg exposure including cardiovascular effects were
      considered. At that time, the committee concluded that neurodevelopmental
      toxicity was the most sensitive endpoint but recognized emerging evidence of
      potential cardiovascular effects at low levels of exposure. The committee
      recommended that these potential effects be addressed through the uncertainty
      factors applied to the development of the neurodevelopmental reference dose
      (RfD). This approach was adopted by the US EPA in its derivation of the
      methylmercury RfD. Since that time, additional studies have become available. The
      available studies addressing the broad categories of heart disease (including
      myocardial infarction (MI) and ischemic heart disease), hypertension, and heart
      rate variability are critically reviewed here. Overall, the evidence linking
      realistic rates of MeHg exposure from fish consumption to cardiovascular disease
      suggests an association with heart disease, particularly MI. The apparent
      antagonistic interaction of MeHg and n-3 fatty acids contained in fish suggests a
      causal mechanism. As different individuals and populations characteristically
      consume different species of fish, the risk of cardiovascular effects may not be
      a simple function of MeHg exposure but its assessment may well need to take n-3
      fatty acid intake into account also. The case for significant adverse effects of
      MeHg on blood pressure at current levels of exposure is weaker. This effect,
      observed in childhood, does not appear to persist into adolescence, and animal
      studies are difficult to interpret given the high doses employed. The decrease in
      heart rate variability related to fetal exposure to MeHg in the same cohort
      appears to persist into early adolescence and may reflect developmental
      neurophysiological alterations that are consistent with the developmental
      neuropsychological effects also observed in that cohort. However, the
      cardiovascular significance of this effect with regard to its direct effect on
      health or its ability to predict other, more direct, health effects is unclear.
      At present, the studies of the Finnish cohort relating MeHg exposure to acute MI
      and coronary heart disease appear to provide the strongest basis for a formal
      quantitative risk assessment of the cardiovascular effects of MeHg.

PMID- 15721895
TI  - Cost analysis of ELISA, solid-phase extraction, and solid-phase microextraction
      for the monitoring of pesticides in water.
AB  - The implementation of a pesticide water monitoring program in South Africa is
      limited by a lack of financial and analytical resources. A cost analysis of three
      analytical methods, enzyme-linked immunosorbent assays (ELISA), solid-phase
      microextraction (SPME), and traditional solid-phase extraction methods (SPE), was
      conducted. The cost analysis assumed a hypothetical scenario in terms of the
      sampling area (a grape farming rural region in the Western Cape province of South
      Africa), sample collection (weekly grab samples collected from eight sites by an
      environmental health officer in a nearby town), transport of samples (via
      courier), and analysis (endosulfan and chlorpyrifos analysis conducted by a local
      higher educational institution laboratory in Cape Town). The cost per sample for
      the three analytical methods was determined by estimating the annual capital
      costs, including building and equipment, and recurrent costs, including
      transport, personnel, supplies, and building operating costs. At the optimal
      utility of resources, SPME had the lowest cost per sample (US $37), followed by
      SPE (US $48.50) and ELISA (US $60). Recurrent costs formed the bulk of the costs
      of all three methods (91-97%). The cost of supplies was particularly high for
      ELISA (US $34 per sample). The cost per sample estimated for all three methods is
      substantially lower than those quoted by other laboratories in South Africa. The
      low cost of SPME is particularly important because of the sensitivity and
      reliability of this method and the faster output compared to SPE, and SPME is
      recommended for the long-term monitoring of pesticide pollution.

PMID- 15721896
TI  - Sorption of divalent metal ions on CrPO4.
AB  - The divalent metal ion sorption (Cu(2+), Cd(2+), Ni(2+), and Pb(2+)) on chromium
      phosphate (CrPO(4)) was studied as a function of pH, temperature, and
      concentration of metal ions. The sorption of metal ions is observed to increase
      with the increase in pH, temperature, and concentration of metal ions in
      solution. The mechanism of sorption is found to be the exchange of the hydrolyzed
      metal cations with the protons from solid at high temperature. The sorption at
      low temperature is found to be accompanied by the precipitation of the
      corresponding metal phosphates such as Pb(3)(PO(4))(2).

PMID- 15721897
TI  - Studies on the adsorption of Brij-35 and CTAB at the coal-water interface.
AB  - The adsorption behavior of polyoxyethylene (23) lauryl ether (Brij-35) and cetyl
      trimethyl ammonium bromide (CTAB) on coal sample has been studied. The adsorption
      process is found to be sensitive to pH, temperature, electrolyte concentration,
      and the amount of surface active agent. An attempt has been made to explain the
      adsorption behavior of the surfactants using the Langmuir equation. The extent of
      adsorption of Brij-35 on coal is found to be the highest at pH 2, which decreases
      with increase in pH and remains constant in the neutral and alkaline pH regions.
      But, the adsorption of CTAB exhibits the opposite behavior of that of Brij-35.
      Adsorption of any of the surfactant at the coal/water interface sharply decreases
      the apparent viscosity of 55 wt% coal-water slurry (CWS) at a shear rate of 100
      s(-1). Electrostatic adsorption of the surfactants on the coal surface decreases
      the surface charge and renders the coal surface hydrophobic which is manifested
      in the form of high apparent viscosity of the coal-water slurry under the test
      conditions.

PMID- 15721899
TI  - Role of copper chloride on the surface of activated carbon in adsorption of
      methyl mercaptan.
AB  - In this paper, adsorption characteristics of methyl mercaptan on virgin activated
      carbon and copper chloride impregnated activated carbons were studied by using a
      dynamic adsorption method in a fixed bed. The activated carbons were
      characterized by nitrogen adsorption, XRD, TGA and solubility tests. The
      impregnation of copper chloride on the activated carbon significantly enhanced
      the adsorption capacity of methyl mercaptan, despite a notable decrease in
      microporosity. It is likely that copper chloride may act as adsorption site for
      methyl mercaptan. Copper chloride on the activated carbon in a range of 3-20 wt%
      Cu content was present mostly in the amorphous form of CuCl(2), according to the
      results of the solubility, XRD and TGA tests. Starting at 10 wt% in Cu loading,
      the adsorption capacity for methyl mercaptan decreases gradually. It is likely
      that a decrease in the degree of copper chloride dispersion and an accessibility
      of small pores may lead to the decrease in the adsorption capacity of the
      activated carbon for methyl mercaptan.

PMID- 15721898
TI  - Metal-modified silica adsorbents for removal of humic substances in water.
AB  - As novel adsorbents for humic substances, Fe-, Mg-, and Ca-modified silica gels
      SiO(2)Fe, SiO(2)Mg, and SiO(2)Ca were prepared, and their adsorbabilities to
      humic and fulvic acids were evaluated in water at 25 degrees C for 20 h. Among
      these adsorbents, SiO(2)Fe indicated the highest adsorbability, in which removing
      humic substances in water was accomplished to 80-97%. By calcination at 600
      degrees C and washing with water, adsorbabilities of the silica adsorbents
      deteriorated except for the case of calcination of SiO(2)Ca. This is due to
      changing metal modification structures and losing chlorine, judging from
      elemental analysis, TG-DTA, and XPS. Especially, the modifier Fe was tightly
      fixed on the silica surface of SiO(2)Fe, since the metal content was almost
      constant even after the calcination and water washing unlike the other
      adsorbents. Therefore, we found that SiO(2)Fe is the most useful adsorbent among
      the silica adsorbents and that its modification structure is composed of SiOFe,
      FeCl, and FeOH. In addition, the adsorption mechanism is explained by an
      interaction between Fe and humic substance molecule having carboxylate and
      phenolate groups, accompanied with anion exchange of chloride ion Cl(-) for the
      humic substance molecule via the silica pores. SiO(2)Fe may be applied to an
      adsorbent alternative for charcoal in water purification plants, and the used
      SiO(2)Fe may be further reused as a fertilizer since humic substances have plant
      glowing ability and silica strengthens plant parts.

PMID- 15721900
TI  - The adsorption of Cu(II) ions on bentonite--a kinetic study.
AB  - The kinetics of sorption of Cu(2+) on a Saudi clay mineral (bentonite) was
      investigated at 20+/-0.5 degrees C using different weights of the clay (0.5, 1.0,
      1.5, and 2 g). Each weight represents a certain sample size. The order of the
      process appeared to be 1 with respect to the Cu(2+), and 112 with respect to the
      clay surface area. The rate was found to depend on internal diffusion.,which
      produced a decrease in the specific rate of sorption as a function of time.
      Sorption characteristics were described using two site Langmuir isotherms. The
      desorption experiments proved that Cu(2+) ions are chemisorbed on the bentonite
      surface. The maximum adsorption obtained was 909 mg Cu(2+)/g clay. This value is
      of great significance, as it is much higher than any reported one.

PMID- 15721901
TI  - Monolayer formation of PBLG-PEO block copolymers at the air-water interface.
AB  - Physicochemical properties of PBLG (poly(gamma-benzyl-l-glutamate))-PEO
      (poly(ethylene oxide)) diblock copolymers composed of PBLG as the hydrophobic rod
      component and PEO as the hydrophilic component were investigated at the air-water
      interface. Surface pressure-area isotherms obtained by the Wilhelmy plate method
      provide several variables such as molecular size, compressibility of PEO, and the
      free energy change of the PBLG-PEO block copolymer. GE-1 (M(w) of
      PBLG:PEO=103,700:12,000), with a relatively longer rod, has negative temperature
      effects and GE-3 (M(w) of PBLG:PEO=8400:12,000), with a relatively shorter rod,
      shows a positive temperature effect because of the large entropy loss. These
      competitions were based on the block size of PBLG and PEO and were affected by
      various microstructures of the PBLG-PEO diblock copolymer. Monolayer aggregations
      transferred onto mica from the air-water interface were analyzed with AFM. AFM
      images of GE-1 monolayers show cylindrical micelles, but the self-assembled
      structure has many large domains. The monolayer of GE-2 (M(w) of
      PBLG:PEO=39,800:12,000), which has a medium size rod, forms a spherical structure
      at the air-water interface. Monolayers of GE-3, with a short rod length, form
      bilayer structures. These results demonstrate that the microstructures of PBLG
      PEO diblock copolymers are related to free energy changes between rod and coil
      blocks.

PMID- 15721903
TI  - Physicochemical characterization of chitosan nanoparticles: electrokinetic and
      stability behavior.
AB  - Some physical properties of nanogel particles formed by chitosan ionically cross
      linked by tripolyphosphate (TPP) have been studied. Electrokinetic properties and
      colloidal stability were analyzed as a function of pH and ionic strength of the
      medium. Chitosan particles showed volume phase transitions (swelling/shrinking
      processes) when the physicochemical conditions of the medium were changed.
      Experimental data were mainly obtained by electrophoretic mobility measurements
      and by photon correlation spectroscopy and static light scattering techniques.
      Chitosan chains possess glucosamine groups that can be deprotonated if the pH
      increases. Therefore, modification of pH from acid to basic values caused a
      deswelling process based on a reduction of the intramolecular electric repulsions
      inside the particle mesh. Electrophoretic mobility data helped to corroborate the
      above electrical mechanism as responsible for the size changes. Additionally, at
      those pH values around the isoelectric point of the chitosan-TPP particles, the
      system became colloidally unstable. Ionic strength variations also induced
      important structural changes. In this case, the presence of KCl at low and
      moderate concentrations provoked swelling, which rapidly turned on particle
      disintegration due to the weakness of chitosan-TPP ionic interactions. These last
      results were in good agreement with the predictions of gel swelling theory by
      salt in partially ionized networks.

PMID- 15721902
TI  - Structured water in partially dehydrated yeast cells and at partially
      hydrophobized fumed silica surface.
AB  - Nonfreezable water structured due to interaction with endocellular objects in
      yeast cells (endocellular water) or with partially hydrophobic fumed silica
      (interfacial water) was studied by means of (1)H NMR spectroscopy with layer-by
      layer freezing-out of bulk water and quantum chemical methods applied to water
      clusters in the gas and liquid (chloroform and cyclohexene) phases and adsorbed
      on silylated silica. Variation in cell hydration as well as in amount of water
      adsorbed on modified fumed silica leads to changes in the ratio between
      contributions of two water states characterized by NMR chemical shifts at
      delta(H)=1.1-1.7 and 4-5 ppm. Lowering of hydration and temperature results in an
      enhancement of the first signal, and the opposite result is observed for the
      second signal. These effects may be explained by structured water distribution in
      the form of relatively large nanodroplets (delta(H)=4-5 ppm is close to that for
      bulk water) and small clusters of the 2D structure, in which the fraction of
      hydrogen atoms out of the hydrogen bonds (delta(H)=1.1-1.7 ppm) is larger than
      that in nanodroplets.

PMID- 15721904
TI  - Surface modification of monodisperse magnetite nanoparticles for improved
      intracellular uptake to breast cancer cells.
AB  - Nanoparticles have been widely used for a variety of biomedical applications and
      there is a growing need for highly specific and efficient uptake of the
      nanoparticles into target cells. Poly(ethylene glycol) (PEG), folic acid (FA),
      and their conjugate PEG-FA were attached to magnetite nanoparticles to compare
      their effects on the improvement of intracellular uptake of the nanoparticles to
      human breast cancer cells, BT-20. AFM and TEM results indicated that the
      nanoparticles after surface modification were monodisperse, with coatings on
      individual nanoparticles. The cell culture experiments showed that the PEG-FA
      coated nanoparticles were internalized into BT-20 cancer cells and exhibited
      higher efficiency of intracellular uptake than only PEG- or FA-coated
      nanoparticles. The surface modification protocols can also be used to modify the
      surfaces of other nanoparticles for targeting intracellular delivery.

PMID- 15721905
TI  - Fengycin interaction with lipid monolayers at the air-aqueous interface
      implications for the effect of fengycin on biological membranes.
AB  - In this study, we investigated the interaction of fengycin, a lipopeptide
      produced by Bacillus subtilis, with lipid monolayers using the Langmuir trough
      technique in combination with Brewster angle microscopy. Thermodynamic analyses
      were performed to get further information about the mixing behavior and the
      molecular interactions between the two components. The effect of fengycin on the
      structural and morphological characteristics of DPPC monolayers, as a simple
      model of biological membranes, depends on the fengycin molar ratio. With a small
      proportion of fengycin (X(f)0.1), the compressibility of the monolayer is
      modified but the morphological characteristics of the DPPC are not significantly
      affected. At an intermediate molar ratio (0.1<X(f)0.5), fengycin has a fluidizing
      effect on the DPPC monolayer by interacting partially with DPPC molecules. At
      higher molar ratio (X(f)=0.66), fengycin totally dissolves the ordered phase of
      the lipid. These results highlight the capacity of fengycin to perturb the DPPC
      organization and are discussed in relation to fengycin capacity to affect
      biological membranes.

PMID- 15721906
TI  - Controlling submicron-particle template morphology: effect of solvent chemistry.
AB  - Porous solids were obtained from self-assembled deposits of silica particles used
      as templates to form 3-D porous membranes. The effect of the solvent chemistry on
      the morphology of the deposits was investigated. The parameters of interest are
      surface tension and ionic strength of the solvent, as they impact electrostatic
      and capillary interactions. Deposits of particles of different sizes were
      obtained from a variety of conditions. The deposits were imaged by SEM and showed
      distinctive structures for each of the solvent chemistries. The phenomenon is
      qualitatively consistent with DLVO theory and calculations of capillary
      interaction energy as developed by Kralchevsky and co-workers.

PMID- 15721907
TI  - Swelling behavior of organoclays in styrene and exfoliation in nanocomposites.
AB  - Organoclays were prepared by cationic exchange of montmorillonite (MMT) with
      three commercial surfactants: octadecylamine (ODA), hexadecyltrimethylammonium
      bromide (HTAB), benzalkonium chloride (BAC), and an in-house synthesized
      surfactant, vinylbenzylalkyldimethylammonium chloride (VDAC). The swelling
      behaviors of organoclays in styrene were compared by wettability and rheology
      measurements. VDAC-MMT had the slowest capillary rise rate in styrene. The
      Washburn equation was found not suitable for the swellable organoclay powders.
      All organoclay-styrene and organoclay-toluene mixtures demonstrated yield stress.
      However, VDAC-MMT-styrene and VDAC-MMT-toluene mixtures showed significant higher
      yield stresses than the other organoclay mixtures. The wettability and rheology
      measurements indicate that VDAC-MMT bearing a styryl functional group has the
      strongest interaction with styrene monomer and toluene. In order to further
      evaluate the extent of swelling and the microstructure, polystyrene (PS)-clay
      nanocomposites were prepared by in situ polymerization. X-ray diffraction (XRD)
      and transmission electron microscopy (TEM) indicate that ODA and HTAB-MMT led to
      intercalated PS-clay nanocomposites, while VDAC-MMT formed exfoliated PS-clay
      nanocomposites.

PMID- 15721908
TI  - Preparation of ZnO colloids by aggregation of the nanocrystal subunits.
AB  - Colloidal ZnO particles with narrow size distribution were prepared via a sol-gel
      process by base-catalyzed hydrolysis of zinc acetate. The morphology of ordered
      arrays of the particles was recorded by SEM. SEM also reveals that these uniform
      particles were composed of tiny ZnO subunits (singlets) sized of several
      nanometers. The size of the singlets, which is confirmed by X-ray diffraction and
      UV-vis absorption spectra, increases as the aging time is prolonged. The size
      selective formation of colloids by aggregation of nanosized subunits is proposed
      to consist of two-stage growth by nucleation of nanosized crystalline primary
      particles and their subsequent aggregation into polycrystalline secondary
      colloids. The aggregates are all spherical because the internal rearrangement
      processes are fast enough. The ZnO colloids, i.e., the aggregates, tend to self
      assemble into well-ordered hexagonal close-packed structures. Room-temperature
      photoluminescence was characterized for green and aged ZnO.

PMID- 15721909
TI  - Interfacial-chemistry mediated behavior of colloidal talc dispersions.
AB  - Interfacial chemistry and rheological behavior of talc suspensions as a function
      of pH, talc solid content, and type and concentration of ions have been
      investigated using electrokinetic measurements, rheology, settling behavior, and
      solution analysis. Zeta potential measurements show a strong dependence on the pH
      history of the talc suspension that only occurs when the surface area (solid
      content) of the talc is high. Particle interactions measured through dispersion
      yield stress measurements show a similar dependence. Talc is a magnesium silicate
      mineral and the dependence seen in the electrokinetic properties in this study
      has been attributed to Mg(II) dissolution at low pH, and has been confirmed by
      solution analysis. At high solid content (>20 wt%), pronounced Mg(II) ion
      dissolution occurs at low pH values. Formation and adsorption of electropositive
      Mg(II) hydrolysis products occurs at high pH (>9), and these lead to zeta
      potential reduction and, at high solid contents, charge reversal. Particle
      interactions reflect the surface chemistry behavior. Consequently, for a freshly
      prepared suspension at high pH, the yield stress is lower compared to after the
      pH has been taken to 5 and subsequently increased.

PMID- 15721911
TI  - Revised state diagram of Laponite dispersions.
AB  - We propose a state diagram of charged disk-like mineral particle (Laponite)
      dispersions as a function of the Laponite concentration (C) and the concentration
      of added salt (C(s)), based on simple observation and light-scattering
      measurements. At low C or high C(s) the dispersions separate into two domains due
      to sedimentation of Laponite aggregates, while at high C and low C(s) they form
      homogeneous gels that do not flow upon tube reversal. The aggregation rate and
      the structure factor of the Laponite dispersions is determined with light
      scattering as a function of C and C(s). We discuss in detail the controversy on
      the origin of gelation of Laponite dispersions in the absence of added salt. We
      argue that aggregation rather than glass formation causes gelation.

PMID- 15721910
TI  - Silica coating of silver nanoparticles using a modified Stober method.
AB  - Silver nanoparticles prepared through a borohydride-reduction method were
      directly coated with silica by means of a seeded polymerization technique based
      on the Stober method. Various amine catalysts were used for initialization of a
      sol-gel reaction of TEOS with no need for a prior surface modification. Use of
      dimethylamine (DMA) as a catalyst was found to be necessary to obtain a proper
      coating. The silica shell thickness was varied from 28 to 76 nm for TEOS
      concentrations of 1-15 mM at 11.1 M water and 0.8 M DMA. The optical spectra of
      the core-shell silver-silica composite particles show a qualitative agreement
      with predictions by Mie theory.

PMID- 15721912
TI  - Cationic-modified cyclodextrin nanosphere/anionic polymer as
      flocculation/sorption systems.
AB  - Simultaneous removal of dissolved and colloidal substances has been a challenging
      task. The cationic-modified beta-cyclodextrin nanospheres synthesized in this
      work, in conjunction with a water-soluble polyacrylamide-based anionic polymer,
      potentially provide a novel approach to address the problem. The cyclodextrin was
      rendered cationic using (2,3-epoxypropyl)trimethylammonium chloride as a reagent.
      The cationicity of the modified cyclodextrin and the reaction between
      cyclodextrin and the reagent were characterized by electrophoresis measurement,
      polyelectrolyte titration, and NMR. As a dual-component flocculation system, the
      cationic cyclodextrin/anionic polymer significantly induced clay flocculation,
      lowering the relative turbidity of the clay suspension over a wide pH range.
      Meanwhile, as a nanospherical absorbent, the modified cyclodextrins exhibited
      strong affinity toward aromatic compounds via inclusion complex formation in the
      hydrophobic cavities, which was monitored by UV spectroscopy. These systems
      facilitated the simultaneous removal of dissolved and colloidal substances, which
      was unachievable previously. In addition, the interaction between anionic
      polymers and the clay particles pretreated with cationic cyclodextrin was
      investigated in order to reveal the flocculation mechanism.

PMID- 15721914
TI  - Phase transfer of oleic acid capped Ni(core)Ag(shell) nanoparticles assisted by
      the flexibility of oleic acid on the surface of silver.
AB  - The phase transfer protocols in vogue for the oleic acid capped silver
      nanoparticles, viz., salt-induced precipitation and redispersion or phosphoric
      acid-induced method, are examined and compared thoroughly. A comprehensive
      evaluation with respect to the mechanistic aspects involved is made and the
      merits and demerits of the different procedures are delineated. It is found that
      the salt-induced precipitation and redispersion is more versatile in that the
      precipitate can actually be redispersed in both aqueous and organic media.
      However, in terms of mechanism both the routes seem to be very similar wherein
      the orientational change of oleic acid on the silver surface in the two different
      environments-organic and aqueous-plays a crucial role in the adaptability of the
      system to the different environments. Subsequently, this change of orientation of
      oleic acid on silver surface in aqueous and organic media has been utilized to
      phase transfer Ni-based nanoparticulate systems. The nascent oleic acid-capped Ni
      nanoparticles, which were synthesized by a foam-based protocol, were dispersible
      in water but not in nonpolar organic media such as cyclohexane or toluene. Then,
      just by coating a thin shell of silver on them we could achieve complete phase
      transfer of the Ni(core)Ag(shell) from aqueous to organic media following similar
      procedures used for oleic acid-capped silver nanoparticles. Here, the phase
      transfer seems to be facilitated by the orientational flexibility of oleic acid
      on the silver surface as opposed to other metal surfaces as evidenced from the
      infrared and thermogravimetric analyses of oleic acid-capped Ni and
      Ni(core)Ag(shell) nanoparticles. This orientation-assisted phase transfer method
      could be generalized and can be adapted to other systems where, if the nascent
      nanoparticles cannot be phase transferred as is, they can be coated by a silver
      shell and oleic acid making them suitable for dispersion in both aqueous and
      organic media.

PMID- 15721913
TI  - The feasibility of inert colloidal processing of silicon nanoparticles.
AB  - Silicon nanoparticles have important applications, including nonvolatile floating
      gate memory devices. To prevent device performance variations, particle size and
      oxide thicknesses need to be controlled with a high degree of precision.
      Additionally, producing well-ordered, two-dimensional arrays of nanoparticles may
      require the exploitation of self-assembly techniques and colloidal forces, which
      in turn requires that silicon nanoparticles first come into contact with liquids.
      Until recently, aerosol silicon nanoparticle collection into liquid was assumed
      to be an inert process. Once formed, the silicon nanoparticle colloid was assumed
      to be inert. In fact, silicon nanoparticles produced in the aerosol phase by
      dilute silane pyrolysis and size classified with a differential mobility analyzer
      undergo a size reduction upon collection in ethylene glycol, water, and ethanol.
      Unclassified polydisperse silicon aerosol nanoparticles with an average diameter
      of 11 nm become monodisperse when collected in a colloid and have a final
      particle diameter of 2-5 nm. Further evidence suggests that silicon nanoparticles
      collected in ethanol react with the ethanol to produce tetraalkylorthosilicate
      like species. Collections of aerosol silicon nanoparticles in degassed water do
      not show measurable differences between the aerosol and colloidal size
      distributions. This reduced reactivity to the solvent indicates that the presence
      of dissolved oxygen in the solvent may be responsible for the reactivity between
      the silicon nanoparticles and the solvent.

PMID- 15721915
TI  - Effects of vinyl series polymers on the formation of hematite particles in a
      forced hydrolysis reaction.
AB  - The influence of polymers on the formation of hematite particles from forced
      hydrolysis of acidic FeCl(3) solution was investigated using vinyl series
      polymers with different functional groups. The disk-like hematite particles were
      produced from forced hydrolysis of acidic FeCl(3) solution in the presence of
      polyvinyl alcohol (PVA: 0-1 wt%). On the other hand, spherical particles were
      produced by addition of very small amounts of polyacrylamide (PAAm: 0-0.004 wt%).
      The size of spherical particles was slightly decreased with increase in the
      concentration of PAAm. The ellipsoidal particles were precipitated by addition of
      a very low concentration of polyacrylic acid (PAAc: 0-0.004 wt%). The effect of
      polymers on the hematite particle formation was expressed in the order of
      PVA<PAAm<PAAc that is in the reverse order from their average molecular weight.
      Therefore it was concluded that the effects of polymer molecules strongly depend
      on the functional groups of polymers. The secondary reduction steps of the
      concentration of Fe(3+) ions ([Fe]) were observed during aging. This secondary
      step of [Fe] corresponded to the time of the complete phase transformation from
      beta-FeOOH to hematite. Thus one was forced to conclude that the dissolution of
      beta-FeOOH particles is a rate-determining step in the reaction sequence for the
      systems with polymers. A rotational particle preparation procedure suggested that
      the morphology of hematite particle is governed by the mode and strength of
      polymer adsorption onto beta-FeOOH and polynuclear primary particles.

PMID- 15721916
TI  - Influence of configuration of carboxylic acid capping ligands on the salt-induced
      aggregation of gold clusters.
AB  - Oxalic acid (Ox) and 1,2,3,4-cyclobutanetetracarboxylic acid (CBTCA) were
      employed as capping ligands in the preparation of gold colloids. FTIR indicated
      that Ox adopted a linear configuration through one oxygen atom and one gold atom,
      while CBTCA adopted a bridge configuration through two oxygen atoms and two gold
      atoms. Ox-gold colloids exhibited aggregation upon addition of NaClO(4), while
      they remained as isolated particles upon NaCl. For CBTCA-gold colloids, not
      NaClO(4) but NaCl resulted in aggregation. The reversed results were considered
      to have been influenced by the different configurations of Ox and CBTCA, which
      were combined results of the Lewis basicity and steric hindrance of the added
      ions.

PMID- 15721917
TI  - Preparation and adsorption properties of monodisperse chitosan-bound Fe3O4
      magnetic nanoparticles for removal of Cu(II) ions.
AB  - Monodisperse chitosan-bound Fe(3)O(4) nanoparticles were developed as a novel
      magnetic nano-adsorbent for the removal of heavy metal ions. Chitosan was first
      carboxymethylated and then covalently bound on the surface of Fe(3)O(4)
      nanoparticles via carbodiimide activation. Transmission electron microscopy
      micrographs showed that the chitosan-bound Fe(3)O(4) nanoparticles were
      monodisperse and had a mean diameter of 13.5 nm. X-ray diffraction patterns
      indicated that the magnetic nanoparticles were pure Fe(3)O(4) with a spinel
      structure, and the binding of chitosan did not result in a phase change. The
      binding of chitosan was also demonstrated by the measurement of zeta potential,
      and the weight percentage of chitosan bound to Fe(3)O(4) nanoparticles was
      estimated to be about 4.92 wt%. The chitosan-bound Fe(3)O(4) nanoparticles were
      shown to be quite efficient for the removal of Cu(II) ions at pH>2. In
      particular, the adsorption rate was so fast that the equilibrium was achieved
      within 1 min due to the absence of internal diffusion resistance. The adsorption
      data obeyed the Langmuir equation with a maximum adsorption capacity of 21.5 mg
      g(-1) and a Langmuir adsorption equilibrium constant of 0.0165 L mg(-1). The pH
      and temperature effects revealed that the adsorption capacity increased
      significantly with increasing pH at pH 2-5, and the adsorption process was
      exothermic in nature with an enthalpy change of -6.14 kJ mol(-1) at 300-330 K.

PMID- 15721918
TI  - Raman spectroscopic study on the structure of water in aqueous solution of
      alpha,omega-amino acids.
AB  - The structure and hydrogen bonding of water in an aqueous solution of various
      alpha,omega-amino acids were analyzed using the contours of the OH stretching in
      the polarized Raman spectra. From the relative intensity of the collective band
      (C value) corresponding to a long-range coupling of the OH stretching in the
      aqueous amino acid solutions, the number of hydrogen bonds disrupted due to the
      presence of one amino acid molecule (N(corr) value) was evaluated. The N(corr)
      value for glycine was slightly positive, whereas with an increase in the number
      of methylene groups between ammonium and carboxylate groups, the N(corr) value
      gradually increased. These results suggest that the species with proximal anionic
      and cationic groups do not disturb the hydrogen-bonded network structure of water
      significantly, probably due to the counteraction of the electrostatic hydration
      effect attributable to the anionic and cationic groups.

PMID- 15721919
TI  - SERS of C60/C70 on gold-coated filter paper or filter film influenced by the gold
      thickness.
AB  - SERS of C(60)/C(70) adsorbed on gold nanoparticles coated on filter paper or
      filter film was studied. As a new SERS substrate, dried gold-coated filter paper
      or filter film has a high SERS activity, whose enhancement factor can be up to
      about 10(5), because it avoided the influence of solvents in C(60)/C(70) solution
      and water in gold hydrosols. The influence of the gold thickness coated on filter
      paper or filter film to SERS of C(60)/C(70) adsorbed on gold nanoparticles was
      mainly discussed. It is indicated that the SERS effect of C(60)/C(70) was very
      sensitive to the distribution and aggregated characteristics of gold
      nanoparticles, and the SERS intensity of each mode increased at its own
      proportion, but it integrally tended to saturation when the thickness of
      colloidal gold coatings increased.

PMID- 15721920
TI  - Morphological and structural characteristics of diazo dyes at the air-water
      interface: in situ Brewster angle microscopy and polarized UV/vis analysis.
AB  - A morphological analysis is presented for Langmuir films of the diazo dyes Sudan
      4 (S4), Sudan 3 (S3), and Sudan red (SR), using Brewster angle microscopy. Stable
      nonmonomolecular structures are formed at the air-water interface denoted as a
      plateau in the pressure-area isotherms. Monolayer domains are evident by the
      contrastless image even before the pressure onset, which grow in size until it
      reached a condensed monolayer. This behavior resembles that of Langmuir films
      from simple aromatic fatty acids. Films from all the azo dyes display similar
      features, according to the surface potential isotherms and in situ polarized
      UV/vis spectroscopy except for the larger area per molecule occupied by S4 and
      SR. This is attributed to the presence of CH(3) groups that cause steric
      hindrance modifying the organization of diazo dye molecules at the air-water
      interface. UV/vis polarized absorption spectroscopy showed preferential
      orientation of S4 and S3 on the water surface, while SR molecules lie
      isotropically. For these three diazo dyes, film absorption was negligible at very
      large areas per molecule, becoming nonzero only at a critical area coinciding
      with the onset of surface potential. The critical area is ascribed to the
      formation of a H-bonded network between water molecules and diazo dye headgroups.

PMID- 15721921
TI  - Effects of the molar ratio of hydroxide and fluoride to Al(III) on fluoride
      removal by coagulation and electrocoagulation.
AB  - The effect of the molar ratio of hydroxide and fluoride ions to Al(III) ions
      (gamma(OH) and gamma(F)) on coagulation and electrocoagulation (EC) was studied
      to solve the problem of the over addition of acid or base. The efficiency of
      defluoridation was approximately 100% when the sum of gamma(OH) and gamma(F)
      (gamma(OH+F)) was close to 3. This finding reveals that the fluoride ions and the
      hydroxide ions can co-precipitate with Al(III) ions and the formula of the
      precipitate is Al(n)F(m)(OH)(3n-m). However, when gamma(OH) was less than 2.4,
      the defluoridation efficiency, given that gamma(OH+F)=3, dropped as gamma(OH)
      fell, because the amount of aluminum polymer formed dropped. The efficiency of
      defluoridation of EC exceeded that of coagulation for equal gamma(OH) and
      gamma(OH+F), when gamma(OH+F)>3, proving the existence of an electrocondensation
      effect.

PMID- 15721922
TI  - Influence of electrostatic interaction on fibrinogen adsorption on gold studied
      by imaging ellipsometry combined with electrochemical methods.
AB  - Imaging ellipsometry was combined with electrochemical methods for studying
      electrostatic interactions of protein and solid surfaces. The potential of zero
      charge for gold-coated silicon wafer/solution interfaces wad determined by AC
      impedance method. The potential of the gold-coated silicon wafer was controlled
      at the potential of zero charge, and the adsorption of fibrinogen on the
      potential-controlled and non-controlled surfaces was measured in real time at the
      same time by imaging ellipsometry. The effect of electrostatic interaction was
      studied by comparing the difference between the potential of controlled
      adsorption and the potential of noncontrolled adsorption. It was shown that the
      rate of fibrinogen adsorption on the potentiostatic surface was faster than that
      on the nonpotentiostatic surface. The electrostatic influence on fibrinogen
      adsorption on the gold-coated silicon wafer was weak, so the hydrophobic
      interaction should be the major affinity.

PMID- 15721923
TI  - Enhanced efficiency of dye-sensitized TiO2 solar cells (DSSC) by doping of metal
      ions.
AB  - Doped TiO(2) semiconductor powders were synthesized using Al and W as
      photovoltaic property-enhancing impurities. Al-doped TiO(2) electrodes increased
      open-circuit voltage (V(oc)), but reduced short-circuit current (I(sc)). In
      contrast, W-doped TiO(2) had an opposite effect. However, dye-sensitized solar
      cell efficiency fabricated with doped TiO(2) was remarkably better than that of
      undoped TiO(2). It seems that these phenomena were related to electrical surface
      state modifications induced by metal-ion dopants. These modifications led to
      significant changes in powder aggregation, charge transfer kinetics, and dye
      adsorption characteristics. The highest efficiency was found by using (Al+W)
      doped TiO(2) nanopowders.

PMID- 15721924
TI  - Synthesis and properties of supramolecular systems based on silica.
AB  - The synthesis of mono-tosyl-beta-cyclodextrin (Ts-beta-CD) and its attachment to
      the surface of aminopropylsilica are reported. The resulting material was
      characterized by IR spectroscopy, elemental analysis, and quantitative evaluation
      of the surface compounds. The maximum amount of beta-cyclodextrin (beta-CD)
      grafted on the surface of silica was 60% of the computer-calculated value. The
      uptake of Cu(II), Cd(II), and Pb(II) ions by this modified material as a function
      of the pH and salt concentration in the aqueous phase was investigated. It is
      shown that the silica modified with beta-CD has a much greater capacity to uptake
      these ions than the starting materials. The formation of grafted inclusion
      compounds of beta-cyclodextrin molecules with polymeric hydroxo complexes of
      metal cations is demonstrated.

PMID- 15721925
TI  - Encapsulation and retention of decanoic acid in sol-gel-made silicas.
AB  - Porous sol-gel-made silica particles are investigated as encapsulation matrices
      for controlled release of substances in food and pharmaceutical applications.
      Here the retention performance of an entrapped model flavor, decanoic acid,
      inside silica matrices made by hydrolysis of tetraethyl orthosilicate (TEOS) is
      studied. The retention of decanoic acid is measured by gas chromatography and
      thermogravimetric analysis. The morphology, specific surface area, porosity, and
      pore size distribution of the particle matrix is controlled by the sol-gel
      preparation method. During drying, the weakly cross-linked polymers in a slowly
      hydrolyzing silica gel deform and wrap around flavor molecules, creating a denser
      gel structure. There the flavor molecules are entrapped more efficiently than in
      fast-hydrolyzing matrices that result in more porous particles. Kinetic annealing
      studies show that flavor molecules are entrapped quite efficiently even at high
      temperatures.

PMID- 15721926
TI  - Ozonation of activated carbons: Effect on the adsorption of selected phenolic
      compounds from aqueous solutions.
AB  - The impact of ozonation on textural and chemical surface characteristics of two
      granular activated carbons (GAC), namely F400 and AQ40, and their ability to
      adsorb phenol (P), p-nitrophenol (PNP), and p-chlorophenol (PCP) from aqueous
      solutions have been studied. The porous structure of the ozone-treated carbons
      remained practically unchanged with regard to the virgin GAC. However, important
      modifications of the chemical surface and hydrophobicity were observed from FTIR
      spectroscopy, pH titrations, and determination of pH(PZC). As a rule, the ozone
      treatment at either room temperature (i.e., about 25 degrees C) or 100 degrees C
      gave rise to acidic surface oxygen groups (SOG). At 25 degrees C primarily
      carboxylic acids were formed while a more homogeneous distribution of carboxylic,
      lactonic, hydroxyl, and carbonyl groups was obtained at 100 degrees C. The
      experimental isotherms for phenolic compounds on both GAC were analyzed using the
      Langmuir model. Dispersive interactions between pi electrons of the ring of the
      aromatics and those of the carbon basal planes were thought to be the primary
      forces responsible for the physical adsorption whereas oxidative coupling of
      phenolic compounds catalyzed by basic SOG was a major cause of irreversible
      adsorption. The exposure of both GAC to ozone at room temperature decreased their
      ability to adsorb P, PNP, and PCP. However, when ozone was applied at 100 degrees
      C adsorption was not prevented but in some cases (P and PNP on F400) the
      adsorption process was even enhanced.

PMID- 15721927
TI  - Effects of thermal annealing on the structural and optical properties of
      Mg(x)Zn(1-x)O nanocrystals.
AB  - Mg(x)Zn(1-x)O ternary alloy nanocrystals with hexagonal wurtzite structures were
      fabricated by using the sol-gel method. X-ray diffraction patterns, UV-vis
      absorption spectra, and photoluminescence spectra were used to characterize the
      structural and optical properties of the nanocrystals. For as-prepared
      nanocrystals, the band gap increases with increasing Mg content. Weak excitonic
      emission with strong deep-level emission related to oxygen vacancy and interface
      defects is observed in the photoluminescence spectra at room temperature. Thermal
      annealing in oxygen was used to decrease the number of defects and to improve the
      quality of the nanocrystals. In terms of XRD results, the grain sizes of
      nanocrystals increase with increasing annealing temperature and the lattice
      constants of alloy are smaller than those of pure ZnO. The band gap becomes
      narrower with increasing annealing temperature. For Mg(x)Zn(1-x)O nanocrystals
      (x=0.03-0.15) annealed at temperatures ranging from 500 to 1000 degrees C,
      intense near-band-edge (NBE) emissions and weak deep-level (DL) emissions are
      observed. Consequently, the quality of Mg(x)Zn(1-x)O nanocrystals can be improved
      by thermal annealing.

PMID- 15721928
TI  - Discrete model of random-pore aging by wall relief softening.
AB  - A new (discrete) model for random-pore aging in isochoric system with wall relief
      softening is proposed. The main criterion of the evolution of such system is the
      reduction of solid-gas interface area with time. The model allows simulations of
      the evolution of aging porous system with time, and estimations of free energy of
      the system. Equations of the model are used for simulations of the evolution of
      porous system with time. It is shown that the proposed model is effective for
      theoretical studies of processes of pore transformations by aging.

PMID- 15721929
TI  - Weakly nonlinear study of Marangoni instabilities in an evaporating liquid layer.
AB  - We propose a theoretical study of Marangoni driven convection in an evaporating
      liquid layer surmounted by an inert gas-vapor mixture. After reduction of the
      full two-layer problem to a one-sided model we use a Galerkin-Eckhaus method
      leading to a finite set of amplitude equations for the weakly nonlinear analysis
      of the problem. We analyze the stability of the roll, square, and hexagonal
      patterns emerging above the linear stability threshold for a water-air and for an
      ethanol-air system.

PMID- 15721930
TI  - Surface properties and structures of diblock copolymer and homopolymer with
      perfluoroalkyl side chains.
AB  - The surface free energy of diblock copolymer, composed of methyl methacrylate and
      2-perfluorooctylethyl methacrylate (PMMA-b-PFEMA), was compared with that of
      PFEMA homopolymer (P-PFEMA) in correlation with their structures in the solid
      state and in the solution using dynamic contact angle, X-ray photoelectron
      spectroscopy, X-ray diffraction, and dynamic light scattering. The PMMA-b-PFEMA
      film cast from chloroform solution was found to possess very low surface free
      energy (7.8 mJ/m(2)) compared with the surface free energies of the P-PFEMA (8.5
      mJ/m(2)) and the PMMA-b-PFEMA (9.8 mJ/m(2)) films cast from CF(3)CF(2)CHCl(2)
      solutions. These differences in the surface free energy were brought about by the
      variations in their surface structures. The very low surface free energy was
      considered to have originated from the surface segregation of the PFEMA segments
      highly self-assembled by the presence of chloroform.

PMID- 15721931
TI  - Kinetics of N-glutaryl-L-phenylalanine p-nitroanilide hydrolysis catalyzed by
      alpha-chymotrypsin in aqueous solutions of dodecyltrimethylammonium bromide.
AB  - The rate of hydrolysis of N-glutaryl-L-phenylalanine p-nitroanilide (GPNA)
      catalyzed by alpha-chymotrypsin (alpha-CT) has been measured in aqueous solutions
      of dodecyltrimethylammonium bromide (DTAB) at concentrations below and above the
      critical micelle concentration, as well as in the absence of surfactant. Under
      all the conditions employed, the reaction follows a Michaelis-Menten mechanism.
      The presence of the surfactant leads to superactivity below and above the
      critical micelle concentration (CMC), with a maximum reaction rate taking place
      near the CMC when the results are treated in terms of the analytical
      concentration of the substrate. A similar behavior was observed by working with
      the enzyme partially deactivated in the presence of 4 M urea. After correction to
      take into account the partitioning of the substrate between the micelles and the
      external media, the activity of the enzyme tends to remain almost constant above
      the corresponding CMCs. This results from a compensation of a decrease in the
      catalytic constant (k(cat)) and a decrease in the Michaelis constant (K(M)). The
      behavior of alpha-CT in the hydrolysis of GPNA in DTAB solutions is at variance
      with that previously reported for the hydrolysis of 2-naphthyl acetate in
      solutions of the same surfactant (E. Abuin, E. Lissi, R. Duarte, Langmuir 19
      (2003) 5374). An explanation of the different effects of the surfactant on the
      behavior of the enzyme with both substrates is advanced, taking into account the
      complexity of the mechanism of the alpha-CT-mediated reaction, more specifically,
      in terms of different rate-limiting steps for the formation of the measured
      products.

PMID- 15721932
TI  - Association properties of diblock copolymer of ethylene oxide and 1,2-butylene
      oxide: E17B12 in aqueous solution.
AB  - Copolymer E(17)B(12) (E denotes OCH(2)CH(2), B denotes OCH(2)CH(C(2)H(5)), and
      the subscripts denote number-average chain lengths) was prepared by sequential
      oxyanionic polymerization and characterized by GPC (for distribution width) and
      NMR spectroscopy (for absolute composition and chain length). Dynamic and static
      light scattering and rheometry were used to characterize micelles in dilute
      solution and demonstrate the formation of compact micelles at low temperatures
      and of elongated micelles at higher temperatures, the latter being accompanied by
      turbidity of the solution. Rheological methods applied across a range of
      concentrations and temperatures served to demonstrate the formation of worm-like
      micelles. Gels based on entangled worm-like micelles (some of them turbid) and on
      packed compact micelles were identified and their properties were explored.

PMID- 15721933
TI  - Aggregation behaviors of gemini nucleotide at the air-water interface and in
      solutions induced by adenine-uracil interaction.
AB  - Cationic gemini surfactants having nucleotides as counterions (called nucleo
      gemini hereafter) were synthesized and their aggregation behavior at air-water
      surfaces as well as in bulk solutions were studied. Fluid solutions of these
      nucleo-gemini surfactants show transitions to hydrogels upon addition of
      complementary nucleoside bases or other nucleo-gemini surfactants having
      complementary bases as counterions. The FTIR-ATR measurements show that the
      carboxylate groups of uridine form hydrogen bonds with the amine groups of
      adenosine. The aggregation behavior was also confirmed at the air-water interface
      by Brewster angle microscopy as well as surface pressure measurements; the
      monolayer of a gemini nucleotide was observed to undergo a transition to
      multilayers when nucleosides with complementary bases were added into the
      subphase. Isotherm curves of surface pressure monitored in parallel show a
      decrease in molecular area upon addition of such nucleosides.

PMID- 15721934
TI  - Physicochemical investigations of microemulsification of eucalyptus oil and water
      using mixed surfactants (AOT+Brij-35) and butanol.
AB  - Microemulsification of a vegetable oil (eucalyptus) with single and mixed
      surfactants (AOT and Brij-35), cosurfactant of different lipophilicities (isomers
      of butanol), and water were studied at different surfactant and cosurfactant
      mixing ratios. The phase diagrams of the quaternary systems were constructed
      using unfolded and folded tetrahedron, wherein the phase characteristics of
      different ternary systems can be underlined. The microemulsion zone was found to
      be dependent upon the mixing ratios of surfactant and cosurfactant; the largest
      microemulsion zone was formed with 1:1 (w/w) S:CS. The effects of temperature and
      additives (NaCl, urea, glucose, and bile salts of different concentrations) on
      the phase behavior were examined. The mixed microemulsion system showed
      temperature insensitivity, whereas the Brij-35 (single) stabilized system
      exhibited a smaller microemulsion zone at elevated temperature. NaCl and glucose
      increased the microemulsion zone up to a certain concentration, beyond which the
      microemulsion zones were decreased. These additives decreased the microemulsion
      zones as temperature was increased. The effect of urea on microemulsion zone was
      found to be insignificant even at the concentration 3.0 mol dm(-3). Little effect
      on microemulsion zone was shown by NaC (sodium cholate) at 0.25 and 0.5 mol dm(
      3) at different temperatures. The conductance of the single (AOT) and mixed
      microemulsion system (AOT+Brij-35) depends upon the water content and mixing
      ratios of the surfactants, and a steep rise in conductance was observed at equal
      weight percentages of oil and water. Viscosities for both single (AOT) and mixed
      (AOT+Brij-35) surfactant systems passed through maxima at equal oil and water
      regions showing structural transition. The viscosities for microemulsion systems
      increased with increasing Brij-35 content in the AOT+Brij-35 blend. Conductances
      and viscosities of different monophasic compositions in the absence and presence
      of additives (NaCl and NaC) were measured at different temperatures. The
      activation energy of conduction (DeltaE(cond)( *)) and the activation enthalpy
      for viscous flow (DeltaH(vis)( *)) were evaluated. It was found that both
      DeltaE(cond)( *) and DeltaH(vis)( *) were a function of the nature of the
      dispersion medium. Considering the phase separation point of maximum solubility,
      the free energy of dissolution of water or oil (DeltaG(s)(0)) at the
      microdispersed state in amphiphile medium was estimated and found to be a
      function of surfactant composition.

PMID- 15721935
TI  - The influence of sodium dodecyl sulfate/benzyl alcohol/H2O system on the
      photoisomerization of trans-stilbene.
AB  - Photoisomerization of trans-stilbene (TS) was investigated in sodium dodecyl
      sulfate (SDS)/benzyl alcohol (BA)/H(2)O systems in order to establish the
      relationship between the reaction yields and the compositions and structures of
      molecular organized assemblies. The results show that, in SDS/BA/H(2)O systems
      with the structures of oil in water microemulsions, bicontinuous microemulsions,
      and hexagonal liquid crystals, the reaction yields are much larger than those in
      benzyl alcohol, both with and without the photosensitizer 9,10
      anthracenedicarbonitrile. However, SDS/BA/H(2)O water in oil microemulsion and
      lamellar liquid crystal can obviously catalyze the photoisomerization of TS only
      when the photosensitizer is not present. The yield is increased with the increase
      in H(2)O content or with the decrease in BA content.

PMID- 15721936
TI  - Effect of silica colloids on the rheology of viscoelastic gels formed by the
      surfactant cetyl trimethylammonium tosylate.
AB  - The effects of the addition of submicrometer-sized colloidal silica spheres on
      the linear and nonlinear rheology of semidilute solutions of a viscoelastic gel
      are studied. For a 1.4 wt% solution of the surfactant CTAT, a peak in the zero
      shear rate viscosity eta(0) is observed at approximately equal weight percents of
      silica and CTAT. This peak shifts to lower silica concentrations on increasing
      either the CTAT concentration or the surface charge on silica and disappears when
      the CTAT concentration is increased to 2.6 wt%. The increases in eta(0) and the
      high frequency plateau modulus G(0) on the introduction of SiO(2) are explained
      by considering the increasingly entangled wormlike micelles that are formed due
      to the enhanced screening of the electrostatic interactions. The observed
      decrease in the values of G(0) and eta(0) at higher concentrations of silica
      particles is explained in terms of the formation of surfactant bilayers due to
      the adsorption of the positively charged cetyl trimethylammonium to the
      negatively charged silica.

PMID- 15721937
TI  - Boundary effect on electrophoresis: finite cylinder in a cylindrical pore.
AB  - The boundary effect on electrophoresis is investigated by considering a finite
      cylindrical particle moving along the axis of a long cylindrical pore under
      conditions of low surface potential and weak applied electric field. The
      influence of the thickness of the double layer, the aspect ratio of a particle,
      the ratio particle radius/pore radius, and the charged conditions of the surfaces
      of the particle and pore on the electrophoretic behavior of a particle are
      investigated. We show that the effect of the aspect ratio of a particle on its
      electrophoretic behavior for the case where the particle is charged and the pore
      is uncharged is larger than that for the case where the particle is uncharged and
      the pore is charged. Also, depending on the parameters chosen, increasing the
      aspect ratio of a particle can either promote or hinder its movement, which is
      not reported in previous studies, and can play a role in electrophoresis
      measurements. Because both the electric and the flow fields in the gap between
      the particle and the pore are mediated by those near the top and the end of the
      particle, the end effect is large when the double layer is thick.

PMID- 15721939
TI  - Sample container temperature gradient influence on the BET specific surface area.
AB  - Differences between BET specific surface area (BET SSA) values exist due to data
      collected in stainless steel and less thermally conductive sample holders. Not
      accounting for the temperature gradient along stainless steel sample holders
      during manometric gas adsorption measurements at cryogenic temperatures leads to
      errors of up to 3.2% in the BET SSA values with a relative combined standard
      uncertainty (RCSU) of 0.63%. A unidimensional heat flow model accurately accounts
      for the temperature gradient, leading to an agreement of 0.16% between the BET
      SSA values for both sample holder units.

PMID- 15721938
TI  - Deposition of gold nanoparticles on silica spheres by electroless metal plating
      technique.
AB  - A previously proposed method for metal deposition with silver [Kobayashi et al.,
      Chem. Mater. 13 (2001) 1630] was extended to uniform deposition of gold
      nanoparticles on submicrometer-sized silica spheres. The present method consisted
      of three steps: (1) the adsorption of Sn(2+) ions took place on surface of silica
      particles, (2) Ag(+) ions added were reduced and simultaneously adsorbed to the
      surface, while Sn(2+) was oxidized to Sn(4+), and (3) Au(+) ions added were
      reduced and deposited on the Ag surface. TEM observation, X-ray diffractometry,
      and UV-vis absorption spectroscopy revealed that gold metal nanoparticles with an
      average particle size of 13 nm and a crystal size of 5.1 nm were formed on the
      silica spheres with a size of 273 nm at an Au concentration of 0.77 M.

PMID- 15721940
TI  - Structure of synthetic calcium hydroxyapatite particles modified with
      pyrophosphoric acid.
AB  - Synthetic colloidal calcium hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2): CaHap) was
      treated with pyrophosphoric acid (H(4)P(2)O(7): PP) in acetone and the materials
      were characterized by XRD, TEM, FTIR, and N(2) and H(2)O adsorption measurements.
      XRD patterns and morphology of CaHap particles were essentially not changed by
      the modification. The additional amount of PO(4) of CaHap was increased with an
      increase of PP concentration and the Ca/P molar ratio of the particles decreased
      from 1.62 to 0.81. IR results indicated that the isolated surface POH band
      developed with increasing the PP concentration up to 6.0 mmol dm(-3) by the
      reaction of isolated surface POH groups of CaHap and pyrophosphoric acids. Above
      10.2 mmol dm(-3), a hydrogen-bonding surface POH band appeared at 2913 cm(-1) and
      enlarged with increasing the PP concentration, while the isolated surface POH
      band was weakened. The results of N(2) and H(2)O adsorption measurements revealed
      that the modified particles aggregated compared to the unmodified ones, which
      would be due to the formation of hydrogen-bonding surface POH groups among the
      particles.

PMID- 15721941
TI  - Near-infrared spectroscopic method for the sensitive and direct determination of
      aggregations of surfactants in various media.
AB  - A new cmc determination method based on a NIR spectroscopic technique has been
      developed. Comparing to other cmc determination methods, this NIR method is
      universal, sensitive, nonintrusive and nonadditive; namely, it can be used for
      the direct measurements of cmc of normal micelles as well as reversed micelles,
      without adding any dye or fluorescent probe. cmc values of various surfactants
      including CTAB, SDS, Triton X-100, Brij-35, Brij-700, Tween-20, SB-12, SB3-10
      determined by this method agree very well with those determined by other methods.
      Additionally, the method can be used for the sensitive and direct determination
      of cmc values of various nonionic surfactants in room-temperature ionic liquids
      including [BMIm](+)[PF(6)](-) and [EMIm](+)[Tf(2)N](-). The preliminary results
      presented here clearly demonstrate that it is possible to use the NIR technique
      not only to characterize aggregation of surfactants in RTILs but also to
      determine kinetics and to identify products of reactions in RTILs as well as in
      microreactors provided by micelles in the RTILs.

PMID- 15721942
TI  - Identification of an EcoRI restriction site for a rapid and precise determination
      of beta-asarone-free Acorus calamus cytotypes.
AB  - Calamus (Acorus calamus L., Araceae) is an aromatic herb, indigenous to Central
      Asia and Eastern Europe. The fragrant oils obtained by alcoholic extraction of
      the rhizome are mainly used in the pharmaceutical and oenological industries.
      Nevertheless, the occurrence of beta-asarone [(Z)-1,2,4-trimethoxy-5-prop-1-enyl
      benzene] limits the possibility of its use due to the carcinogenic properties of
      this compound. The aim of this work was to identify a diploid beta-asarone-free
      A. calamus by using chemical and molecular approaches. For these purposes
      alcoholic extracts of both diploid and triploid A. calamus were analyzed by gas
      chromatography-mass spectrometry (GC-MS) and comparison of the 700 bp sequence of
      the non-transcribed spacer (NTS) in the 5S-rRNA gene was also performed.
      Alcoholic extracts of the triploid A. calamus were characterized by a higher
      percentage of beta-asarone (11%), which was the main compound, followed by higher
      percentages of camphene (2.27%), E-beta-ocimene (3.28%), camphor (1.54%),
      calarene (1.42%), alpha-selinene (5.02%) and tau-cadinol (2.00%), when compared
      to the diploid A. calamus. The latter had higher percentages of iso-shyobunone
      (8.62%), beta-sesquiphellandrene (3.28%), preiso calamendiol (22.81%) and acorone
      (26.33%), and completely lacked of beta-asarone. The 5S-rRNA spacer region of
      both diploid and triploid A. calamus were amplified by PCR using a pair of
      primers located at the 3' and 5' ends of the coding sequence of 5S-rRNA gene. The
      resulting PCR products (about 700 bp) were gel purified, subcloned into pGEM-T
      Easy vector and sequenced. By aligning the isolated nucleotide sequences of the
      two varieties and the sequences from different A. calamus chemotypes present in
      Genbank, sequence diversities were found in the spacer region. Furthermore, the
      PCR products were digested by using EcoRI. The restriction profile of the spacer
      domain resulted different for the two cytotypes. Along with chemical analysis of
      alcoholic extracts, sequence analysis coupled to restriction mapping was
      demonstrated to represent a powerful tool to distinguish the A. calamus diploid
      cytotype from the others. The security and effective usage of the diploid beta
      asarone-free A. calamus was also discussed.

PMID- 15721944
TI  - Analysis of polyamine metabolism in soybean seedlings using 15N-labelled
      putrescine.
AB  - The translocation and metabolism of polyamines during soybean germination were
      studied using 15N-labelled putrescine as a precursor. Both 15N-labelled and
      unlabelled polyamines were simultaneously detected using a novel application of
      ionspray ionization-mass spectrometry. 15N-putrescine was rapidly transported to
      the shoots and roots, where it was converted to spermidine and spermine. The main
      15N-polyamine that accumulated in the root was 15N-spermine. It was found that
      there were differences in the way endogenous putrescine and exogenous 15N
      putrescine were metabolized in soybean seedlings.

PMID- 15721943
TI  - Purification and cloning of a gamma-glutamyl transpeptidase from onion (Allium
      cepa).
AB  - Gamma-glutamyl transpeptidase (E.C. 2.3.2.2; GGT) catalyses hydrolysis of gamma
      glutamyl linkages in gamma-glutamyl peptides and transfer of the gamma-glutamyl
      group to amino acids and peptides. Although plant gamma-glutamyl peptide
      metabolism is important in biosynthesis and metabolism of secondary products and
      xenobiotics, plant GGTs are poorly characterised. We purified a membrane
      associated GGT from sprouting onion bulbs that catalyses transpeptidation of
      methionine by the synthetic substrate gamma-glutamyl-p-nitroanilide (GGPNA) and
      obtained N-terminal peptide sequence. We also cloned the full-length coding
      region of an onion GGT by homology with the Arabidopsis enzyme and confirmed that
      this shared the same N-terminal sequence. Enzyme kinetic studies show that the
      enzyme has high affinity for glutathione and glutathione conjugates, and that
      affinity for S-substituted glutathione analogs decreases as the substituted chain
      length increases. The major onion gamma-glutamyl peptide, gamma-glutamyl trans-S
      1-propenyl cysteine sulfoxide (GGPrCSO) exhibited uncompetitive inhibition of
      transpeptidation by GGPNA. This suggests that GGPrCSO is a poor glutamyl donor
      and therefore unlikely to be an in vivo substrate for peptidase activity by this
      enzyme.

PMID- 15721945
TI  - Mass spectral characterization of fatty acid amides from alfalfa trichomes and
      their deterrence against the potato leafhopper.
AB  - A homologous series of N-(3-methylbutyl)amides of normal saturated C14, C15, C16,
      C17 and C18 fatty acids were identified as major components of glandular trichome
      extracts from Medicago sativa G98A, an alfalfa genotype resistant to the potato
      leafhopper, Empoasca fabae. A second homologous series of N-(2
      methylpropyl)amides of C14 through C18 normal fatty acids were minor components.
      Saturated free fatty acids C12, C13, C14, C15, C16, C17 and C18 were present in
      trace amounts, as was the N-(3-methylbutyl)amide of linoleic acid (C18:2). N-(3
      methylbutyl)amides and N-(2-methylpropyl)amides of C14 through C18 fatty acids,
      along with the N-(3-methylbutyl)amide of linoleic acid, were synthesized and
      bioassayed for leafhopper deterrence by applying the compounds to the surface of
      a sachet containing an artificial diet. Leafhoppers were then offered a two-way
      choice between diet surfaces treated with the synthetic amides or an untreated
      control. N-(3-methylbutyl)amides and N-(2-methylpropyl)amides of C14 through C18
      fatty acids did not deter leafhopper settling in a dose-dependent fashion. In
      contrast, when tested singly, N-(3-methylbutyl)amide of linoleic acid exhibited
      dose-dependent deterrence against leafhopper settling. Fatty acid amides
      localized in alfalfa glandular trichomes likely contribute to leafhopper
      resistance.

PMID- 15721947
TI  - Chemotaxonomy of the Rubiaceae family based on leaf fatty acid composition.
AB  - With 10,700 species distributed in 637 genera, the Rubiaceae family is one of the
      largest of the angiosperms. Since it was previously evidenced that the fatty acid
      composition of photosynthetic tissues can be a tool for chemotaxonomic studies,
      the fatty acid composition of leaves from 107 Rubiaceae species highly
      representative of the diversity of the family was determined. Principal component
      analysis allowed a clear-cut separation of Coffeae, Psychotrieae and Rubieae. The
      occurrence of C16:3 fatty acid, a marker of the prokaryotic plastidial lipid
      biosynthetic pathway, concerned at least two branches: Theligoneae/Rubieae and
      Anthospermeae-Anthosperminae which appeared to be in close relationship.
      Additional experiments were carried out to ensure the correlation between the
      presence of C16:3 fatty acid and the prokaryotic biosynthetic pathway.

PMID- 15721946
TI  - Leucine aminopeptidase M inhibitors, cyanostatin A and B, isolated from
      cyanobacterial water blooms in Scotland.
AB  - Two leucine aminopeptidase M inhibitors, cyanostatin A and B, were isolated from
      cyanobacterial water blooms at Loch Rescobie in Scotland, and specifically from a
      Microcystis species. Both inhibitors were lipopeptides containing 3-amino-2
      hydroxydecanoic acid and weak inhibitors of protein phosphatase (PP2A). Both
      strongly inhibited the activity of leucine aminopeptidase M with IC50 values of
      40 and 12 ng/ml, respectively.

PMID- 15721948
TI  - Genetic diversity of UPASI tea clones (Camellia sinensis (L.) O. Kuntze) on the
      basis of total catechins and their fractions.
AB  - Tea leaf catechins and the ratio of dihydroxylated to trihydroxylated catechin
      fractions were analysed to identify the genetic diversity of 26 UPASI released
      tea clones. Principal component analysis (PCA) based on regression factor
      separated tea clones into five groups according to their jats (Jats are region
      based rays for e.g., Assam, China and Cambod origin) as well as their quality
      constituents (such as total polyphenols, total catechins, amino acids in the
      green leaves and liquor characteristics of black tea), particularly the
      catechins. Group 1 represented medium quality (quality of the final produce)
      clones, such as UPASI-10, UPASI-12 and UPASI-15 and drought tolerant clones like
      UPASI-1, UPASI-2, UPASI-9 and UPASI-10. Group 2 contained purely "China"
      cultivars while group 3 possessed high quality tea cultivars. "Assam" (group 5)
      teas had the lowest ratio of dihydroxylated to trihydroxylated catechin fractions
      (1:4) than the "Chinery" (group 2) teas (1:5). This biochemical differentiation
      indicated that there is a vast genetic diversity in UPASI released tea clones in
      terms of catechin fractions, even though the majority of them were selected from
      one tea estate located in the Nilgiris.

PMID- 15721949
TI  - Chemical constituents of Murraya siamensis: three coumarins and their anti-tumor
      promoting effect.
AB  - Isolation and structure elucidation of three coumarins, murrayacoumarins A, B,
      and C, together with eight known coumarins, from the leaves of Murraya siamensis
      Craib collected in Thailand are described. Results of a primary screening of
      inhibitory effects of seven of these compounds on 12-O-tetradecanoylphorbol-13
      acetate-induced Epstein-Barr virus early antigen activation in Raji cells are
      also presented.

PMID- 15721950
TI  - Chromenes of polyketide origin from Peperomia villipetiola.
AB  - An extract of leaves and stems of Peperomia villipetiola has been found to
      contain myristicin (3-methoxy-4,5-methylenedioxy-allylbenzene) and seven
      chromenes, whose structures are methyl 5-hydroxy-7-methyl-2,2-dimethyl-2H-1
      chromene-6-carboxylate (1), methyl 5-methoxy-7-methyl-2,2-dimethyl-2H-1-chromene
      8-carboxylate (2), methyl 7-hydroxy-5-methyl-2,2-dimethyl-2H-1-chromene-6
      carboxylate (3), methyl 7-methoxy-5-methyl-2,2-dimethyl-2H-1-chromene-6
      carboxylate (4), 5-methanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylic
      acid (5), 5-methanol-7-methoxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (6),
      and methyl 5-acetoxymethanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate
      (7). A biosynthetic rationale for 1-7 suggests that orsellinic acid may be a
      common intermediate. The anti-fungal activities of the chromenes were measured
      bioautographically against Cladosporium cladosporioides and Cladosporium
      sphaerospermum: compounds 6 and 7 were found to be the most active.

PMID- 15721951
TI  - Synthesis and bioactivity of C-29 brassinosteroid analogues with different
      functional groups at C-6.
AB  - In this paper, we report the synthesis and bioactivity of four synthetic
      analogues of 28-homobrassinosteroids, in order to evaluate the influence in
      bioactivity when the C-6 keto group is replaced by different functional groups.
      The synthetic analogues are 6-deoxo-28-homocastasterone [(22R,23R)-stigmasta
      2alpha,3alpha,22,23-tetraol], 6alpha-hydroxy-28-homocastasterone [(22R,23R)
      stigmasta-2alpha,3alpha,6alpha,22,23-pentaol], 6beta-hydroxy-28-homocastasterone
      [(22R,23R)-stigmasta-2alpha,3alpha,6beta,22,23-pentaol], and [(22R,23R)-6alpha
      fluorostigmasta-2alpha,3alpha,22,23-tetraol]. Results indicate that replacement
      of the 6-keto moiety by an beta or alpha hydroxyl group led to a decrease in
      activity, whereas the 6-deoxo analogue showed a very low activity, confirming the
      importance of an electronegative moiety at C-6 to observe hormonal potency. The
      6alpha-fluorinated analogue elicited a low activity, similar to that of the 6
      deoxo analogue.

PMID- 15721952
TI  - Further constituents from the bark of Tabebuia impetiginosa.
AB  - Further study on the constituents from the bark of Tabebuia impetiginosa (Mart.
      ex DC) Standley afforded twelve compounds, consisting of four iridoid glycosides,
      one phenylethanoid glycoside, five phenolic glycosides, and one lignan glycoside,
      along with seven known compounds. The structures of these compounds were
      determined based on the interpretation of their NMR and MS measurements and by
      chemical evidence.

PMID- 15721953
TI  - Sesquiterpene constituents from the essential oil of the liverwort Plagiochila
      asplenioides.
AB  - The essential oil of the liverwort Plagiochila asplenioides from two different
      locations in Northern Germany were investigated by chromatographic and
      spectroscopic methods. Seven compounds were isolated by preparative gas
      chromatography (GC) and their structures investigated by mass spectrometry (MS),
      NMR techniques and chemical correlations in combination with enantioselective GC.
      In addition to known constituents, aromadendra-1(10),3-diene, two aromatic
      sesquiterpene hydrocarbons, bisabola-1,3,5,7(14)-tetraene and bisabola-1,3,5,7
      tetraene, three sesquiterpene ethers, muurolan-4,7-peroxide, plagiochilines W and
      X, in addition to ent-4-epi-maaliol, could be identified as natural compounds for
      the first time.

PMID- 15721954
TI  - Evidence of formation of glushinskite as a biomineral in a Cactaceae species.
AB  - The X-ray diffractometric and infrared spectroscopic investigation of crystalline
      material isolated from the Cactaceae species Opuntia ellisiana shows the presence
      of a very complex mineral composition, including whewellite (monohydrated calcium
      oxalate), opal (SiO2), calcite (CaCO3) and glushinskite (dihydrated magnesium
      oxalate). This is the first report of the presence of magnesium oxalate in
      plants.

PMID- 15721955
TI  - Concrete spatial language: see what I mean?
AB  - Conveying complex mental scenarios is at the heart of human language. Advances in
      cognitive linguistics suggest this is mediated by an ability to activate
      cognitive systems involved in non-linguistic processing of spatial information.
      In this fMRI-study, we compare sentences with a concrete spatial meaning to
      sentences with an abstract meaning. Using this contrast, we demonstrate that
      sentence meaning involving motion in a concrete topographical context, whether
      linked to animate or inanimate subjects nouns, yield more activation in a
      bilateral posterior network, including fusiform/parahippocampal, and
      retrosplenial regions, and the temporal-occipital-parietal junction. These areas
      have previously been shown to be involved in mental navigation and spatial memory
      tasks. Sentences with an abstract setting activate an extended largely left
      lateralised network in the anterior temporal, and inferior and superior
      prefrontal cortices, previously found activated by comprehension of complex
      semantics such as narratives. These findings support a model of language, where
      the understanding of spatial semantic content emerges from the recruitment of
      brain regions involved in non-linguistic spatial processing.

PMID- 15721956
TI  - Cerebral lateralization and general intelligence: gender differences in a
      transcranial Doppler study.
AB  - The present study evaluated cerebral lateralization during Raven's progressive
      matrices (RPM) paradigm in female and male subjects. Bilateral simultaneous
      transcranial Doppler (TCD) ultrasound was used to measure mean blood flow
      velocities (MBFV) in the right and left middle cerebral arteries (MCAs) in 24 (15
      females and 9 males) right-handed normal subjects. The female subjects used a
      left hemisphere strategy, while males used a right hemisphere strategy to
      successfully solve RPM tasks. This implies that general intelligence is
      associated with neural systems within one hemisphere that are accessible to a
      variety of cognitive processes.

PMID- 15721957
TI  - Is problem solving dependent on language?
AB  - There has been a long-standing debate in the fields of philosophy and cognitive
      science surrounding the relationship of language to cognition, but the exact
      nature of this relationship is still unclear (Sokolov, 1968/1972). In the current
      study, we explored the role of language in one aspect of cognition, namely
      problem solving, by administering the Wisconsin Card Sorting Test (WCST) to
      stroke patients with varying degrees of language impairment (Experiment 1) and to
      normal participants under conditions of articulatory suppression (Experiment 2).
      In Experiment 1, there was a significant correlation between performance on the
      WCST and language measures such as comprehension and naming. Demonstrating the
      specificity of this result, we also found a significant relationship between
      language performance and another test of problem solving, the Raven's Colored
      Progressive Matrices, but no relationship between language and a test of
      visuospatial functioning. In Experiment 2, normal participants were significantly
      impaired on the WCST under conditions of articulatory suppression, relative to a
      baseline condition. Together, these findings suggest that language plays a role
      in complex problem solving, possibly through covert language processes.

PMID- 15721959
TI  - Language effects in magnitude comparison: small, but not irrelevant.
AB  - It is assumed that number magnitude comparison is performed by assessing
      magnitude representation on a single analog mental number line. However, we have
      observed a unit-decade-compatibility effect in German which is inconsistent with
      this assumption (Nuerk, Weger, & Willmes, 2001). Incompatible magnitude
      comparisons in which decade and unit comparisons lead to different responses
      (e.g., 37_52 for which 3<5, but 7>2) are slower and less accurately responded to
      than compatible trials in which decade and unit comparisons lead to the same
      response (e.g., 42_57, for which 4<5 and 2<7). As overall distance was held
      constant, a single holistic magnitude representation could not account for this
      compatibility effect. However, because of the inversion property of the
      corresponding German two-digit number words ("einundzwanzig" <one-and-twenty>),
      the language-generality of the effect is questionable. We have therefore examined
      the compatibility effect with native English speakers. We were able to replicate
      the compatibility effect using Arabic notation. Thus, the compatibility effect is
      not language-specific. However, in cross-linguistic analyses language-specific
      modulations were observed not only for number words but also for Arabic numbers.
      The constraints imposed on current models by the verbal mediation of Arabic
      number comparison are discussed.

PMID- 15721958
TI  - A critical boundary to the left-hemisphere advantage in visual-word processing.
AB  - Two experiments explored boundary conditions for the ubiquitous left-hemisphere
      advantage in visual-word recognition. Subjects perceptually identified words
      presented directly to the left or right hemisphere. Strong left-hemisphere
      advantages were observed for UPPERCASE and lowercase words. However, only a weak
      effect was observed for AlTeRnAtInG-cAsE words, and a numerical reversal of the
      typical left-hemisphere advantage was observed for words in a visual prototype
      font (a very unfamiliar word format). Results support the theory that dissociable
      abstract and specific neural subsystems underlie visual-form recognition and fail
      to support the theory that a visual lexicon operates in the left hemisphere.

PMID- 15721960
TI  - The relationship between phonological and morphological deficits in Broca's
      aphasia: further evidence from errors in verb inflection.
AB  - A previous study of 10 patients with Broca's aphasia demonstrated that the
      advantage for producing the past tense of irregular over regular verbs exhibited
      by these patients was eliminated when the two sets of past-tense forms were
      matched for phonological complexity (Bird, Lambon Ralph, Seidenberg, McClelland,
      & Patterson, 2003). The interpretation given was that a generalised phonological
      impairment was central to the patients' language deficits, including their poor
      performance on regular past tense verbs. The current paper provides further
      evidence in favour of this hypothesis, on the basis of a detailed analysis of the
      errors produced by these same 10 patients in reading, repetition, and sentence
      completion for a large number of regular, irregular, and nonce verbs. The
      patients' predominant error types in all tasks and for all verb types were close
      and distant phonologically related responses. The balance between close and
      distant errors varied along three continua: the severity of the patient (more
      distant errors produced by the more severely impaired patients); the difficulty
      of the task (more distant errors in sentence completion>reading>repetition); the
      difficulty of the item (more distant errors for novel word forms than real
      verbs). A position analysis for these phonologically related errors revealed that
      vowels were most likely to be preserved and that consonant onsets and offsets
      were equally likely to be incorrect. Critically, the patients' errors exhibited a
      strong tendency to simplify the phonological form of the target. These results
      are consistent with the notion that the patients' relatively greater difficulty
      with regular past tenses reflects a phonological impairment that is sensitive to
      the complexity of spoken forms.

PMID- 15721961
TI  - Effects of noun-verb homonymy on the neural correlates of naming concrete
      entities and actions.
AB  - The neural correlates of naming concrete entities such as tools (with nouns) and
      naming actions (with verbs) are partially distinct: the former are linked to the
      left inferotemporal (IT) region, whereas the latter are linked to the left
      frontal opercular (FO) and left posterior middle temporal (MT) regions. This
      raises an intriguing question: How would such neural patterns be influenced by
      noun-verb homonymy, specifically, naming tasks in which the target words denote
      objects or actions (e.g., "comb")? To explore this, we conducted a PET study in
      which 10 normal participants named visually presented tools or actions. The
      factor of homonymy yielded interesting effects: For tools, non-homonymous nouns
      (e.g., "camera") activated left IT, whereas homonymous nouns (e.g., "comb")
      activated both left IT and left FO. For actions, non-homonymous (e.g., "juggle")
      and homonymous (e.g., "comb") verbs activated left FO, MT, and IT, but there was
      evidence that the FO and MT activations were less widespread for the homonymous
      verbs. We also found that retrieval of the same exact words (e.g., "comb" and
      "comb") produced differential activation in left MT-there was greater MT
      activation when the words were being used to name actions, than when they were
      being used to name tools. Our results suggest that noun-verb homonymy has an
      important influence on the patterns of neural activation associated with words
      denoting objects and actions, and that even when the phonological forms are
      identical, the patterns of neural activation are different according to the
      demands of the task.

PMID- 15721962
TI  - Language in benign childhood epilepsy with centro-temporal spikes abbreviated
      form: rolandic epilepsy and language.
AB  - Although Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) has a good
      prognosis, a few studies have suggested the existence of language disorders
      relating to the interictal dysfunction of perisylvian language areas. In this
      study, we focused on language assessment in 16 children aged 6-15 currently
      affected by BECTS or in remission. An important proportion of children showed
      moderate or more severe language impairment. The most affected domains were
      expressive grammar and literacy skills. We found linguistic deficits during the
      course of epilepsy but also persistent deficits in children in remission,
      suggesting possible long-term effects. Our results support the hypothesis that
      BECTS may be associated with impairment to language and suggest the possibility
      of a direct link between epileptic activity and language development, and the
      existence of long-term consequences.

PMID- 15721963
TI  - Lexical retrieval constrained by sound structure: the role of the left inferior
      frontal gyrus.
AB  - Positron emission tomography was used to investigate two competing hypotheses
      about the role of the left inferior frontal gyrus (IFG) in word generation. One
      proposes a domain-specific organization, with neural activation dependent on the
      type of information being processed, i.e., surface sound structure or semantic.
      The other proposes a process-specific organization, with activation dependent on
      processing demands, such as the amount of selection needed to decide between
      competing lexical alternatives. In a novel word retrieval task, word
      reconstruction (WR), subjects generated real words from heard non-words by the
      substitution of either a vowel or consonant. Both types of lexical retrieval,
      informed by sound structure alone, produced activation within anterior and
      posterior left IFG regions. Within these regions there was greater activity for
      consonant WR, which is more difficult and imposes greater processing demands.
      These results support a process-specific organization of the anterior left IFG.

PMID- 15721964
TI  - Modulation of brain activity during phonological familiarization.
AB  - We measured brain activity in 12 adults for the repetition of auditorily
      presented words and nonwords, before and after repeated exposure to their
      phonological form. The nonword phoneme combinations were either of high (HF) or
      low (LF) phonotactic frequency. After familiarization, we observed, for both word
      and nonword conditions, decreased activation in the left posterior superior
      temporal gyrus, in the bilateral temporal pole and middle temporal gyri. At the
      same time, interaction analysis showed that the magnitude of decrease of activity
      in bilateral posterior temporal lobe was significantly smaller for LF nonwords,
      relative to words and HF nonwords. Decrease of activity in this area also
      correlated with the size of behavioral familiarization effects for LF nonwords.
      The results show that the posterior superior temporal gyrus plays a fundamental
      role during phonological learning. Its relationship to sublexical and lexical
      phonological processing as well as to phonological short-term memory is
      discussed.

PMID- 15721965
TI  - Higher-order activity beyond the word level: cortical dynamics of simple
      transitive sentence comprehension.
AB  - Slow electrophysiological effects, which fluctuate throughout the course of a
      sentence, independent of transient responses to individual words, have been
      reported. However, this type of activity has scarcely been studied, and with only
      limited use of electrophysiological information, so that the brain areas in which
      these variations originate have not been clearly identified. To improve this
      state of affairs, a principal component analysis and a modern source analysis
      algorithm (LORETA) were applied to the slow activity underlying transitive
      sentence reading. Four components explained 97.3% of the variance. Of key
      interest was a slow variation that occurred throughout the entire sentence but
      peaked with the appearance of the verb. The main solution for this component was
      localized in prefrontal and temporal regions presumably involved in semantic
      sentence processing. This constitutes empirical evidence for cortical activity-
      related to semantic processes thought to be involved in thematic role assignment-
      developing throughout the sentence but presenting a conspicuous maximum with the
      appearance of the verb. This finding also highlights the central role of verb
      information in the understanding of transitive sentences.

PMID- 15721966
TI  - Palliative care, time, and core values.

PMID- 15721967
TI  - Intervention studies for caregivers of stroke survivors: a critical review.
AB  - The objective of this review was to evaluate the effectiveness of different types
      of intervention programs for caregivers of stroke patients. A systematic search
      using Medline, PsychINFO, AMED and CINAHL till March 2003 was carried out and 22
      studies were identified. Four types of support programs could be studied:
      providing specialist services, (psycho)education, counselling and social support
      by peers. Many different outcome domains and a variety of measures were used. Ten
      studies reported positive results on one or more outcome domains: reduction of
      depression (two studies) and burden (one), improvement of knowledge on stroke
      (five), satisfaction with care (one), family functioning (one), quality of life
      (three), problem solving skills (two), social activities (two), and social
      support (one). Three studies reported a negative result on caregiver outcome. We
      could not identify sufficient evidence to confirm the efficacy of interventions
      but counselling programs (3 out of 4) appear to have the most positive outcome.

PMID- 15721968
TI  - Decision-making in palliative care practice and the need for moral deliberation:
      a qualitative study.
AB  - The development of palliative care is increasing the interest in the moral
      problems that arise in the practice of palliative care. It is not clear how
      caregivers deal with these moral problems. In this article, we focus on the
      decision whether to continue treatment or to withhold it, and discuss the way
      caregivers deal with this question amongst themselves and in communication or
      consultation with the patient. We look at moral deliberation, the process of
      identifying the crucial arguments for this decision in palliative care.

PMID- 15721969
TI  - What do discharged patients know about their medication?
AB  - Patient's knowledge is a necessity for empowering patients to perform self-care,
      especially when dealing with new, ill-defined and unknown situations. The aim of
      this paper is to assess patients' reported as opposed to correct knowledge about
      medication therapy after discharge from hospital and to identify factors that
      increase correct knowledge. Three hundred and forty-one patients were interviewed
      7-14 days after discharge from six internal wards in a large medical facility in
      Israel. Most patients (73%) were aware of the course and purpose of their
      medication. They were, however, unaware of side effects, needed lifestyle
      changes, and correct medication schedules. A large difference was found between
      levels of reported and correct knowledge about various issues regarding
      medication treatment. No significant correlation was found between correct
      knowledge about medication therapy at discharge, and gender, age, education,
      patient satisfaction and wish for more counseling. The only factor which
      significantly affected levels of correct knowledge was whether the patient had
      received medication counseling during hospitalization. The findings illuminate
      the gap between patients' perception of knowledge and actual knowledge. The study
      indicates the need for patient counseling during hospitalization, with respect to
      medication therapy.

PMID- 15721970
TI  - Promoting physical activity in Australian general practices: a randomised trial
      of health promotion advice versus hypertension management.
AB  - A randomised controlled trial was conducted to determine if physicians' advice to
      promote physical activity to patients was more effective if the advice was
      tailored to the management of hypertension, compared with more general health
      promotion advice. Participants included inactive 40- to 70-year-old patients
      visiting the physicians' during study recruitment period. Physicians provided
      verbal physical activity advice and written materials, both tailored to either
      general health promotion messages or specifically as a means for treating or
      managing hypertension. Seventy-five physicians and 98% (767/780) of screened
      eligible patients participated in the study. Differences between intervention and
      control groups self-reported physical activity were assessed over 6 months.
      Follow-up response rates were 92 and 84% at the 2- and 6-month assessments. There
      were no consistent, significant differences between groups at the 2- or 6-month
      assessments. Thus, neither intervention strategy resulted in significant changes
      in patients self-reported physical activity, regardless of the whether the advice
      was tailored to hypertension management or general health promotion advice.

PMID- 15721971
TI  - Visual illusions? Beliefs and behaviours of presbyope clients in optometric
      practice.
AB  - Many clients in optometry practice have reported that they do not receive
      sufficient information from practitioners to make informed purchasing decisions
      for corrective spectacles. The aim of this study was to identify participants'
      attitudes and beliefs towards visiting an optician and purchasing spectacles, to
      compare clients' and practitioners' perceptions of purchasing decisions, and to
      examine clients' preferences for information and decision making. One hundred and
      fifty-eight presbyopes completed a questionnaire to examine attitudes and
      behaviours regarding visiting an optician. Thirty-four practitioners completed a
      questionnaire examining the purchasing recommendations they make to clients, and
      their perceptions of clients' purchasing decisions and information needs.
      Participants reported positive attitudes towards visiting an optician but
      required more information about their eyesight and about purchasing options. A
      discrepancy was found between client and practitioner perceptions of purchasing
      decisions and of involvement in the decision making process. Practitioners
      overestimated the importance of price to clients and underestimated the
      importance of their own recommendations on purchasing decisions. The findings of
      this study could be used to guide practitioners in their provision of information
      to clients.

PMID- 15721972
TI  - Patient evaluation on family doctors' family orientation.
AB  - Family orientation is one of basic features of family practice. The purpose of
      the study was to explore the patients' opinions about family physician
      involvement in family related issues, and to identify the factors that may
      influence the patients' opinions. Altogether 514 patients completed a
      questionnaire. Logistic regression analysis was used to predict the factors which
      determine patient orientation to talk about family related issues. The results
      indicate that the patients' health and the family background influence their
      willingness to talk to family physicians about their family related problems. The
      findings of the study confirm that special attention should be paid to patients
      who definitely have family problems because of chronic illness, or an alcohol or
      drug using family member, or those who are widowed or divorced. Also, the ethnic
      origin was found to have an impact on patient opinions of family physicians'
      family involvement.

PMID- 15721973
TI  - The routine and the traumatic in prenatal genetic diagnosis: does clinical
      information inform patient decision-making?
AB  - With the increasing technical sophistication of medicine, clinicians' task of
      assuring patient informed consent is increasingly elusive. Taking the example of
      prenatal genetic testing, we examine efforts to communicate the complexities of
      genetic knowledge and risk calculation to patients. In this qualitative,
      descriptive study, we interviewed 50 clinicians and 40 patients, and observed 101
      genetic counseling sessions. We found the clinicians and patients have different
      goals, purposes, and values regarding testing, which affect their clinical
      interactions. The information the clinicians provide patients reflects their
      clinical interest in identifying and controlling pathophysiology, while patients,
      in contrast, are most concerned with protecting and nurturing their pregnancy. We
      argue informed patient decision-making about prenatal testing options requires
      information that is responsive to patient interests. We recommend developing a
      shared decision-making approach, to facilitate the full participation of both
      clinicians and patients in the decision-making process.

PMID- 15721974
TI  - Cognitive behavioural group training (CBGT) for patients with type 1 diabetes in
      persistent poor glycaemic control: who do we reach?
AB  - Approximately a quarter of adults with type 1 diabetes do not succeed in
      achieving satisfactory glycaemic control, partly due to problems with the
      demanding self-management regimen. To improve glycaemic control, interventions
      with a cognitive behavioural approach, aimed at modifying dysfunctional beliefs,
      reducing negative emotions and enhancing self-care practices are a potentially
      successful tool. Little is known about the reach of such an approach. This
      article describes characteristics of participants in a randomized, controlled
      trial of cognitive behavioural group training for patients with type 1 diabetes
      in poor glycaemic control. Results show that outpatients from seven hospitals in
      the area of Amsterdam, selected on long-standing high HbA1c and volunteering to
      participate, report high levels of psychological distress and depressive
      symptoms. Furthermore, self-care behaviours were perceived as important, but
      burdensome. Diabetes-specific self-efficacy was relatively low. It is concluded
      that this selected group of adults with type 1 diabetes would potentially benefit
      from a cognitive-behavioural intervention in order to reduce negative emotions,
      enhance diabetes self-efficacy, self-care behaviour and glycaemic outcomes.

PMID- 15721975
TI  - Implementation and effectiveness of a primary care based physical activity
      counselling scheme.
AB  - The aim of the project was to reach inactive people through primary care offices
      and motivate them to become more active for health purposes. Physical activity
      questionnaires based on the transtheoretical model (TM) of behaviour change were
      handed out to every person entering one of five primary care offices. All
      inactive people were entered into a randomised controlled trial (RCT).
      Individuals assigned to the feedback group were given feedback from their
      physician concerning their physical activity level. In addition, the advice plus
      group received further advice and stage matched leaflets and was offered a 45-min
      counselling session. Changes in physical activity behaviour were measured 7 weeks
      as well as 14 months after the intervention. Physicians and patients alike
      reacted positively to the project. Ninety percent of patients entering the
      primary care offices were willing to participate. Ninety percent of inactive
      people agreed to be entered into the RCT. The follow-up rate in this trial was
      82% at 14 months. At 7 weeks, 35% of patients in the feedback group were now
      classified as active and 38% of patients in the advice plus group. At 14 months,
      47% of the subjects in both groups were active. Inactive people can be reached
      effectively through primary care offices. Patients receiving feedback from their
      physician concerning their physical activity level improved their behaviour to
      the same extent as patients who were given further advice and written materials,
      and were offered a counselling session.

PMID- 15721977
TI  - Clinic staff perceptions of tuberculosis treatment delivery in Bali.
AB  - A number of studies have investigated patient perceptions of tuberculosis (TB)
      treatment delivery, but few have systematically investigated the perceptions of
      clinic staff. We therefore conducted individual interviews using Q-methodology
      with 25 staff directly involved in the delivery of TB treatment services in 18
      different public sector health centres in Bali. Factor analysis was used to
      identify shared perceptions of TB treatment delivery in Bali among the sample
      studied. Three distinct perspectives emerged, indicating that all staff do not
      have shared understandings of difficulties and priorities in TB treatment. The
      main areas of difference in staff perceptions concerned the existence of barriers
      to treatment and the focus on the community context of TB treatment. The
      demonstrated variation in the perceptions of TB treatment delivery in Bali has
      important implications for the design of strategies to improve treatment delivery
      and the control of TB.

PMID- 15721976
TI  - Performance of the English and Spanish S-TOFHLA among publicly insured Medicaid
      and Medicare patients.
AB  - The objective of this study was to analyze the psychometric properties of the
      English and Spanish S-TOFHLA for three patient populations of interest. Despite
      being widely used, little is written about psychometric properties of the S
      TOFHLA, particularly the Spanish version. Participants were Medicaid and Medicare
      patients: 936 non-Hispanic and 368 Hispanic patients completed the English S
      TOFHLA; 1066 Hispanics completed the Spanish S-TOFHLA. Validity of both versions
      of the S-TOFHLA was supported by strong positive relationships with education and
      inverse relationships with age. Significant differences between scores for men
      and women remained after adjusting for level of education. Score differences
      occurred across numerous items. More research is needed on the S-TOFHLA and other
      health literacy instruments to determine why women score differently than men.
      Variability in literacy skills within subgroups of patients highlights the
      importance of healthcare providers being sensitive to patients' literacy levels
      in both spoken and written communications.

PMID- 15721978
TI  - An exploratory study of cancer patients' views on doctor-provided and independent
      written prognostic information.
AB  - This is the first study to systematically compare cancer patients' views on
      prognostic information provided by their doctor and written prognostic
      information obtained from a major cancer organisation (The Cancer Council New
      South Wales). Twenty-six adult patients who were recruited from a cancer clinic
      and an oncologist's private rooms completed a questionnaire and an interview.
      Participants varied in their views about the relative accuracy of doctor-provided
      and independent written information and responses to contradictory information.
      Participants' need for certainty, trust in their doctor and concerns about the
      effect of undermining that trust, appear to influence whether they would discuss
      independent information with their doctor, and how they would deal with
      conflicting information. Although preliminary, this study has identified a number
      of issues that may need to be taken into account both by people developing
      written prognostic information and by doctors, who may need to address patient
      concerns about trust to assist patients to deal with conflicting information.

PMID- 15721979
TI  - The powerhouse takes control of the cell: is the mitochondrial permeability
      transition a viable therapeutic target against neuronal dysfunction and death?
AB  - Stroke and neurodegenerative disease exert an increasing large toll on human
      health at the levels both of the individual and of society. As an example of
      each, in the United States, stroke is the major single cause of overall morbidity
      and mortality, and the financial costs of Alzheimer's disease alone dwarfs the
      entire federal medical research budget. It has been long recognized that
      mitochondrial energy production is essential for the second to second functions
      of the central nervous system (CNS), and that severe mitochondrial impairment is
      incompatible with normal cerebral function. The last decade, however, has brought
      a growing understanding that mitochondria play an even greater role than
      previously suspected. Increased understanding of the role of mitochondria in
      antioxidant defense and calcium homeostasis further solidified the importance of
      mitochondria in CNS function--just as increased understanding of mitochondrial
      roles in calcium-mediated toxicity and production of reactive species further
      exemplified the Janus role of mitochondria--as mediators of CNS dysfunction.
      Perhaps most unexpected, however, was the evidence that mitochondria serve as the
      dominant integrators, checkpoints, and amplifiers of the cell death signals in
      the CNS. The mechanism of propagation of cell death cascades by mitochondria
      remains controversial. In this review, we focus on the evidence that supports the
      involvement of an event termed the mitochondrial permeability transition that (i)
      occurs (patho)physiologically; (ii) occurs in the CNS, and; (iii) is a potential
      target for pharmaceutical intervention against CNS dysfunction, injury, and cell
      loss resulting from stroke, trauma, and neurodegenerative disease.

PMID- 15721980
TI  - Biomarkers of oxidative stress study II: are oxidation products of lipids,
      proteins, and DNA markers of CCl4 poisoning?
AB  - Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine
      of rats were measured as part of a comprehensive, multilaboratory validation
      study searching for noninvasive biomarkers of oxidative stress. This article is
      the second report of the nationwide Biomarkers of Oxidative Stress Study using
      acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent
      (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on
      concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA),
      isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8
      hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand
      breaks were investigated to determine whether the oxidative effects of CCl4 would
      result in increased generation of these oxidation products. Plasma concentrations
      of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of
      isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both
      low-dose and high-dose CCl4-treated rats at more than one time point. The other
      urinary markers (MDA and 8-OHdG) showed significant elevations with treatment
      under three of the four conditions tested. It is concluded that measurements of
      MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential
      candidates for general biomarkers of oxidative stress. All other products were
      not changed by CCl4 or showed fewer significant effects.

PMID- 15721981
TI  - Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti
      inflammatory agents indomethacin and meclofenamic acid on measurements of
      oxidative products of lipids in CCl4 poisoning.
AB  - Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes
      were identified as markers of in vivo lipid peroxidation in an animal model of
      CCl4 poisoning. We sought to determine the extent to which the formation of these
      oxidation products is influenced by inhibition of the cyclooxygenase enzymes
      which catalytically generate proinflammatory lipid peroxidation products known as
      prostaglandins and thromboxane. In the present studies, after induction of
      oxidant stress in rats with CCl4, lipid peroxidation products measured in plasma
      and urine demonstrate that isoprostanes and MDA can be partially inhibited by
      cyclooxygenase inhibitors, albeit to different extents. The lowering of
      isoprostane and MDA formation, however, may not to due primarily to the
      diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases
      but, rather, may be the result of the suppression of nonenzymatic lipid
      peroxidation. This is suggested since 8,12-iso-iPF2alpha-VI is also reduced by
      indomethacin, yet, unlike other isoprostanes and MDA, it is not generated
      catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase
      inhibitors we tested have statistically significant effects on the measurements
      of both isoprostanes and MDA in this study, the results provide evidence that
      these lipid-degradation products primarily constitute markers of oxidative
      stress.

PMID- 15721982
TI  - Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation
      product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope
      spreading.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with
      autoantibodies as a near universal feature of the disease. The Ro
      ribonucleoprotein particle, composed of a 60-kDa protein noncovalently associated
      with human cytoplasmic RNA, is the target of antibodies in 25-40% of lupus
      patients. Purified human 60-kDa Ro was found to be oxidatively modified. Earlier
      investigations from our laboratory revealed increased oxidative damage in SLE
      patients. Therefore we hypothesized that oxidation by-products, such as 4-hydroxy
      2-nonenal (HNE), could lead to neoantigens like HNE-modified 60-kDa Ro, which
      could in turn initiate autoimmunity or drive epitope spreading. To test this
      hypothesis we immunized rabbits with either HNE-modified 60-kDa Ro or the
      unmodified Ro. Intramolecular epitope spreading within the Ro molecule and
      intermolecular epitope spreading to La, double-stranded DNA, nRNP, and Sm
      occurred preferentially in HNE-Ro-immunized animals. Nonspecific anti-HNE
      antibody, generated by immunization with HNE-keyhole limpet hemocyanin conjugate,
      did not significantly bind to these autoantigens. These data may suggest a
      hitherto unappreciated mechanism by which oxidative stress facilitates epitope
      spreading in SLE.

PMID- 15721983
TI  - Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning
      in aged mice.
AB  - The main purpose of this study was to determine whether supplemental intake of
      coenzyme Q10 (CoQ) (ubiquinone-10) or alpha-tocopherol, either alone or together,
      could improve brain function of aged mice, as reflected in their cognitive or
      psychomotor performance. Separate groups of aged mice (24 months) were
      administered either CoQ (123 mg/kg/day), or alpha-tocopherol acetate (200
      mg/kg/day), or both, or the vehicle (soybean oil) via gavage for a period of 14
      weeks. Three weeks following the initiation of these treatments, mice were given
      a battery of age-sensitive behavioral tests for the assessment of learning,
      recent memory, and psychomotor function. In a test that required the mice to
      rapidly identify and remember the correct arm of a T-maze, and to respond
      preemptively in order to avoid an electric shock, the intake of alpha-tocopherol
      plus CoQ resulted in more rapid learning compared to the control group. Learning
      was not significantly improved in the mice receiving CoQ or alpha-tocopherol
      alone. None of the treatments resulted in a significant improvement of
      psychomotor performance in the old mice. In a separate study, treatment with
      higher doses of CoQ alone (250 or 500 mg/kg/day) for 14 weeks failed to produce
      effects comparable to those of the combination of alpha-tocopherol and CoQ. The
      apparent interaction of CoQ and alpha-tocopherol treatments is consistent with
      the previous suggestion, based on biochemical studies, that coenzyme Q and alpha
      tocopherol act in concert. Overall, the findings suggest that concurrent
      supplementation of alpha-tocopherol with CoQ is more likely to be effective as a
      potential treatment for age-related learning deficits than supplementation with
      CoQ or alpha-tocopherol alone.

PMID- 15721984
TI  - No evidence of mitochondrial respiratory dysfunction in OGG1-null mice deficient
      in removal of 8-oxodeoxyguanine from mitochondrial DNA.
AB  - Accumulation of high levels of mutagenic oxidative mitochondrial DNA (mtDNA)
      lesions like 8-oxodeoxyguanine (8-oxodG) is thought to be involved in the
      development of mitochondrial dysfunction in aging and in disorders associated
      with aging. Mice null for oxoguanine DNA glycosylase (OGG1) are deficient in 8
      oxodG removal and accumulate 8-oxodG in mtDNA to levels 20-fold higher than in
      wild-type mice (N.C. Souza-Pinto et al., 2001, Cancer Res. 61, 5378-5381). We
      have used these animals to investigate the effects on mitochondrial function of
      accumulating this particular oxidative base modification. Despite the presence of
      high levels of 8-oxodG, mitochondria isolated from livers and hearts of Ogg1-/-
      mice were functionally normal. No differences were detected in maximal
      (chemically uncoupled) respiration rates, ADP phosphorylating respiration rates,
      or nonphosphorylating rates with glutamate/malate or with succinate/rotenone.
      Similarly, maximal activities of respiratory complexes I and IV from liver and
      heart were not different between wild-type and Ogg1-/- mice. In addition, there
      was no indication of increased oxidative stress in mitochondria from Ogg1-/-
      mice, as measured by mitochondrial protein carbonyl content. We conclude,
      therefore, that highly elevated levels of 8-oxodG in mtDNA do not cause
      mitochondrial respiratory dysfunction in mice.

PMID- 15721985
TI  - Alzheimer-specific epitopes of tau represent lipid peroxidation-induced
      conformations.
AB  - Several recent studies support a link between tau protein phosphorylation and
      adduction of tau by reactive carbonyls. Indeed, the phosphorylation-dependent
      adduction of tau by carbonyl products resulting from lipid peroxidation creates
      the neurofibrillary tangle-related antigen, Alz50. To determine whether epitopes
      of carbonyl-modified tau are major conformational changes associated with
      neurofibrillary tangle formation, we examined seven distinct antibodies raised
      against neurofibrillary tangles that recognize unique epitopes of tau in
      Alzheimer disease. Consistently, all seven antibodies recognize tau more strongly
      (4- to 34-fold) after treatment of normal tau with the reactive carbonyl, 4
      hydroxy-2-nonenal (HNE), but only when tau is in the phosphorylated state. These
      findings not only support the idea that oxidative stress is involved in
      neurofibrillary tangle formation occurring in brains of Alzheimer disease
      patients, but also show, for the first time, that HNE modifications of tau
      promote and contribute to the generation of the major conformational properties
      defining neurofibrillary tangles.

PMID- 15721986
TI  - Involvement of mtDNA damage in free fatty acid-induced apoptosis.
AB  - A growing body of evidence indicates that free fatty acids (FFA) can have
      deleterious effects on beta-cells. It has been suggested that the beta-cell
      dysfunction and death observed in diabetes may involve exaggerated activation of
      the inducible form of nitric oxide synthase (iNOS) by FFA, with the resultant
      generation of excess nitric oxide (NO). However, the cellular targets with which
      NO interact have not been fully identified. We hypothesized that one of these
      targets might be mitochondrial DNA (mtDNA). Therefore, experiments were initiated
      to evaluate damage to mtDNA caused by exposure of INS-1 cells to FFA (2/1
      oleate/palmetate). The results showed that FFA caused a dose-dependent increase
      in mtDNA damage. Additionally, using ligation-mediated PCR, we were able to show
      that the DNA damage pattern at the nucleotide level was identical to the one
      induced by pure NO and different from damage caused by peroxynitrite or
      superoxide. Following exposure to FFA, apoptosis was detected by DAPI staining
      and cytochrome c release. Treatment of INS-1 cells with the iNOS inhibitor
      aminoguanidine protected these cells from mtDNA damage and diminished the
      appearance of apoptosis. These studies suggest that mtDNA may be a sensitive
      target for NO-induced toxicity which may provoke apoptosis in beta-cells
      following exposure to FFA.

PMID- 15721987
TI  - Human fecal water content of phenolics: the extent of colonic exposure to
      aromatic compounds.
AB  - Phenolic compounds are not completely absorbed in the small intestine and so
      enter the colon, where they might exert physiological effects. To identify
      phenolics that are present in normal human colon, fecal water was prepared from 5
      free-living volunteers with no dietary restrictions and analyzed by gas
      chromatography-mass spectrometry. Daily measurements were also performed on a
      single individual to examine the variation more closely. Levels of polyphenols
      were variable between individuals. Naringenin and quercetin had mean
      concentrations of 1.20 and 0.63 microM. All other flavonoids examined were
      present < or =0.17 microM. Simple phenolic and other aromatic acids were present
      at much higher concentrations. The major components were phenylacetic acid, 479
      microM; 3-phenylpropionic acid, 166 microM; 3-(4-hydroxy)-phenylpropionic acid,
      68 microM; 3,4-dihydroxycinnamic acid, 52 microM; benzoic acid, 51 microM; 3
      hydroxyphenylacetic acid, 46 microM; and 4-hydroxyphenylacetic acid, 19 microM.
      Other phenolic acids ranged from 0.04 to 7 microM. Decreased dietary phenolic
      intake caused a decrease in polyphenol and monophenolic acid concentration in
      fecal water 24 h later. This study is the first to measure the range of aromatic
      compounds in human fecal water and demonstrates that phenolic acid concentrations
      are high. The biological effects of phenolics may play an important role in colon
      function.

PMID- 15721988
TI  - Alpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and
      limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol
      diets.
AB  - Although all forms of vitamin E are absorbed, the liver preferentially secretes
      alpha-, but not gamma-tocopherol, into plasma. Liver alpha-tocopherol secretion
      is under the control of the alpha-tocopherol transfer protein (TTP). Therefore,
      to assess gamma-tocopherol bioactivities Ttpa-/-, +/- and +/+ mice were fed for 5
      weeks diets containing gamma-tocopherol 550 (gamma-T550), gamma-tocopherol 60
      (gamma-T60) mg/kg that also contained trace amounts of alpha-tocopherol, a
      vitamin E-deficient diet, or a control diet. Plasma and tissues from mice fed
      gamma-T550 diets were found to contain similar gamma- and alpha-tocopherol
      concentrations despite the high dietary gamma-tocopherol content; nervous tissues
      contained almost no gamma-tocopherol. Liver vitamin E metabolites (carboxyethyl
      hydroxychromans, CEHCs) were also measured. In mice with widely ranging liver
      alpha- (from 0.7 to 16 nmol/g) and gamma-tocopherol concentrations (0 to 13
      nmol/g), hepatic alpha-CEHC was undetectable, but gamma-CEHC concentrations (0.1
      to 0.8 nmol/g) were correlated with both alpha- and gamma-tocopherol
      concentrations (P < 0.004). Hepatic cytochrome P450s (CYPs) involved in vitamin E
      metabolism, Cyp4f and Cyp3a, were also measured. There were no variations in
      Cyp4f protein expression as related to diet or mouse genotype. However, Cyp3a was
      correlated (P < 0.0001) with liver alpha-, but not gamma-tocopherol
      concentrations. These data support the hypothesis that alpha-tocopherol modulates
      xenobiotic metabolism by increasing Cyp3a expression, gamma-CEHC formation, and
      the excretion of both gamma-tocopherol and gamma-CEHC.

PMID- 15721989
TI  - Nuclear proteasome activation and degradation of carboxymethylated histones in
      human keratinocytes following glyoxal treatment.
AB  - Nuclear DNA damage has been studied in detail, but much less is known concerning
      the occurrence and fate of nuclear protein damage. Glycoxidation, protein damage
      that results from a combination of protein glycation and oxidation, leads to the
      formation of protein-advanced glycation end products (AGE) of which N(epsilon)
      carboxymethyllysine (CML) is a major AGE. We have used glyoxal, a product of
      environmental exposures that readily leads to the formation of CML, to study
      nuclear protein glycoxidation in HaCaT human keratinocytes. Glyoxal treatment
      that did not affect cell viability but inhibited cell proliferation in a dose
      dependent manner that led to accumulation of CML-modified histones. Modified
      histones were slowly degraded but persisted for more than 3 days following
      treatment. Preincubation of cells with a proteasome inhibitor following glyoxal
      treatment led to an increase in CML-modified histones. While glyoxal treatment
      resulted in a slight decrease in total cellular proteasome activity, a dose
      dependent increase of up to 4-fold in nuclear proteasome activity was observed.
      The increase in nuclear proteasome activity was due to both increased nuclear
      proteasome protein content and increased activity, neither of which were affected
      by cyclohexamide. The increase also was unaffected by inhibitors of poly(ADP
      ribose) polymerases, which have been previously implicated in nuclear proteasome
      activation by oxidizing agents. Accumulation of CML-modified histones over time
      may lead to epigenetic changes that contribute to various pathologies including
      aging and cancer, and upregulation of nuclear proteasome activity under
      conditions of glyoxidative stress may function to limit such damage.

PMID- 15721990
TI  - Tissue-specific changes of mitochondrial functions in aged rats: effect of a long
      term dietary treatment with N-acetylcysteine.
AB  - The understanding of the involvement of mitochondrial oxidative phosphorylation
      (OXPHOS) in the aging process has often been biased by the different
      methodological approaches as well as the choice of the biological material
      utilized by the various groups. In the present paper, we have carried out a
      detailed analysis of several bioenergetic parameters and oxidative markers in
      brain and heart mitochondria from young (2 months) and old (28 months) rats. This
      analysis has revealed an age-related decrease in respiratory fluxes in brain but
      not in heart mitochondria. The age-related decrease in respiratory rate (-43%) by
      NAD-dependent substrates was associated with a consistent decline (-40%) of
      complex I activity in brain mitochondria. On the other hand, heart mitochondria
      showed an age-related decline of complex II activity. Both tissues showed,
      however, an age-associated accumulation of oxidative damage. We have then
      performed the same analysis on old (28 months) rats subjected to a long-term (16
      months) diet containing the antioxidant N-acetylcysteine (NAC). The treated old
      rats showed a slight brain-specific improvement of mitochondrial energy
      production efficiency, mostly with NAD-dependent substrates, together with a
      decrease in carbonyl protein content and an increase in the amount of protein
      thiols of brain cytosolic fraction. A full recovery of complex II activity was
      detected in heart mitochondria from NAC-treated old rats. The present work
      documents the marked tissue specificity of the decline of bioenergetic functions
      in isolated mitochondria from aged rats and provides the first data on the
      effects of a long-term treatment with N-acetylcysteine.

PMID- 15721991
TI  - Enhanced susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      neurotoxicity in high-fat diet-induced obesity.
AB  - Currently, obesity is considered a systemic inflammation; however, the effects of
      obesity on the vulnerability of dopaminergic neurons to oxidative stress are not
      fully defined. We evaluated the effects of high-fat diet-induced obesity (HF DIO)
      on neurotoxicity in mice treated with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). Eight weeks after a HF or matched normal diet, a
      severe decrease in the levels of striatal dopamine and of nigral microtubule
      associated protein 2, manganese superoxide dismutase, and tyrosine hydroxylase
      was observed in obese mice treated with subtoxic doses of MPTP (20 mg/kg)
      compared with the matched lean group. In addition, the levels of nitrate/nitrite
      and thiobarbituric acid-malondialdehyde adducts in the substantia nigra of obese
      mice were reciprocally elevated or suppressed by MPTP. Interestingly, striatal
      nNOS phosphorylation and dopamine turnover were elevated in obese mice after MPTP
      treatment, but were not observed in lean mice. The nitrotyrosine immunoreactivity
      for evaluation of nigral nitrogenous stress in obese mice with MPTP was higher
      than that in matched lean mice. At higher doses of MPTP (60 mg/kg), the mortality
      was higher in obese mice than in lean mice. These results suggest that DIO may
      increase the vulnerability of dopaminergic neurons to MPTP via increased levels
      of reactive oxygen and nitrogen species, and the role of nNOS phosphorylation in
      the MPTP toxicities and dopamine homeostasis should be further evaluated.

PMID- 15721992
TI  - Selective neuronal vulnerability and inadequate stress response in superoxide
      dismutase mutant mice.
AB  - To understand the role of oxidative stress and mitochondrial defects in the
      development of neurodegeneration, we examined the age-related pathological
      changes and corresponding gene expression profiles in homozygous mutant mice
      deficient in the mitochondrial form of superoxide dismutase (MnSOD, SOD2). These
      Sod2-/- mice, generated on a B6D2F1 background, developed ataxia at Postnatal Day
      (P) 11 and progressively deteriorated with frequent seizures by P14.
      Histopathological examination revealed neurodegenerative changes consistent with
      the neurological signs. Vacuolar degeneration was observed in neurons and
      neuropil throughout the brainstem and rostral cortex. The motor trigeminal
      nucleus in brainstem and the deeper layers of the motor cortex were the earliest
      regions to degenerate, with the thalamus and hippocampus affected at later
      stages. Oligonucleotide microarrays were used to compare gene expression profiles
      in the brainstem and thalamus of Sod2+/+ and -/- mice from birth to P18. Notably,
      a large set of heat-shock protein genes was transcriptionally down regulated, and
      this was most likely due to a reduction in the heat-shock transcription factor 1
      (HSF1). Other major classes of differentially expressed genes include lipid
      biosynthesis and ROS metabolism.

PMID- 15721993
TI  - Estrogen as an adjuvant therapy to antipsychotics does not prevent relapse in
      women suffering from schizophrenia: results of a placebo-controlled double-blind
      study.
AB  - The expected therapeutic effect of estrogen as an adjunct treatment to
      antipsychotics in women suffering from schizophrenia for relapse prevention was
      to be tested under real-life conditions. A multicenter, randomized, placebo
      controlled, double-blind, cross-over study based on an A-B-A-B (and/or B-A-B-A)
      design was applied. Forty-six hypoestrogenic women with schizophrenia
      hospitalized for the first time or repeatedly were included in the study. Their
      average age was 37.9 and they had been suffering from schizophrenia for 8.4
      years. During the drug treatment phases, they received a three-phase estrogen
      gestagen combination drug (17beta-estradiol+norethisterone acetate) in addition
      to an antipsychotic drug. Significant effects of the adjuvant hormone replacement
      therapy on the estradiol levels could be observed, and high and low levels of
      estradiol prevailed in the active drug and placebo phases, respectively. We did
      not find any difference either in defined relapse events or in the
      psychopathology between estradiol replacement and placebo phases. Neither did the
      required antipsychotic doses or the tolerance data differ between the two phases.
      Thus, the results of our study do not confirm the hypothesis that a combined
      estradiol/antipsychotic therapy is superior to an antipsychotic monotherapy for
      relapse prevention.

PMID- 15721994
TI  - Voxel-based morphometry versus region of interest: a comparison of two methods
      for analyzing gray matter differences in schizophrenia.
AB  - Many previous studies exploring cortical gray matter (GM) differences in
      schizophrenia have used "region of interest" (ROI) measurements to manually
      delineate GM volumes. Recently, some investigators have instead employed voxel
      based morphometry (VBM), an automated whole-brain magnetic resonance image
      measurement technique. The purpose of the current study was to compare the above
      methods in calculating GM distributions in schizophrenia patients relative to
      matched controls. Using ROIs, Buchanan et al. (Buchanan, R.W., Francis, A.,
      Arango, C., Miller, K., Lefkowitz, D.M., McMahon, R.P., Barta, P.E. and Pearlson,
      G.D., 2004. Morphometric assessment of the heteromodal association cortex in
      schizophrenia. Am J Psychiatry. 161 (2), 322-331.) found decreased dorsolateral
      prefrontal GM volume and altered symmetry of inferior parietal GM in
      schizophrenia patients. We hypothesized that VBM analyses of the same data would
      complement the ROI findings. As predicted, VBM analyses replicated results of
      less left inferior and right superior frontal cortical GM in schizophrenia.
      Additionally, VBM uncovered a significantly lower concentration of GM in the
      middle and superior temporal gyri, sought but not detected using ROIs, but did
      not replicate the parietal changes. The principal explanation for these
      differences may be the methodological differences between voxel-averaged,
      landmark-based ROI analyses and the single, voxel-by-voxel whole brain VBM
      measurements. Although VBM is rapid and fully automated, it is not a replacement
      for manual ROI-based analyses. Both methods provide different types of
      information and should thus be used in tandem.

PMID- 15721995
TI  - Olfactory functions and volumetric measures of orbitofrontal and limbic regions
      in schizophrenia.
AB  - OBJECTIVE: Olfactory deficits in schizophrenia patients have been suggested to
      reflect medial temporal and/or prefrontal brain abnormalities. In this study, we
      examined the relationship between different olfactory functions and volumes of
      the hippocampus-amygdala complex (HAC) and the orbitofrontal brain region using
      magnetic resonance imaging (MRI). METHODS: Thirty-three young men with
      schizophrenia (DSM-IV) and 40 healthy controls performed unirhinal olfactory
      assessment including the main olfactory functions (threshold, discrimination, and
      identification), and odor judgements (intensity, edibility, familiarity, and
      pleasantness). Volumes of regions in the medial temporal lobe (hippocampus and
      amygdala) and the prefrontal region (orbitofrontal gray and white matter) were
      measured on MRI scans. RESULTS: Compared with controls, patients showed
      bilaterally impaired thresholds, quality discrimination and identification, as
      well as edibility judgements. Olfactory deficits were not attributable to
      smoking, premorbid intelligence, or impaired thresholds. Relative to controls,
      patients had bilateral reduced hippocampus and amygdala volumes. In patients,
      smaller hippocampus volumes were associated with poorer olfactory discrimination
      ability. CONCLUSIONS: Olfactory deficits in schizophrenia appear to be associated
      with morphometric abnormalities in the medial temporal rather than the
      orbitofrontal region (OFR). These results indicate that olfactory quality
      discrimination deficits are related to structural hippocampus abnormalities.
      Future studies of genetic and behavioral high-risk samples seem warranted.

PMID- 15721996
TI  - Macroscopic brain asymmetry is changed along the antero-posterior axis in
      schizophrenia.
AB  - BACKGROUND: Anatomical asymmetry may be altered in schizophrenia, but the changes
      are subtle and in some studies undetected perhaps due to methodological
      limitations. METHODS: In a postmortem MRI study (23 patients, 20 controls), we
      used a geometric mesh technique to define the cortical surface and to separate
      two components of brain asymmetry: hemisphere shift, conceived as the position of
      an entire hemisphere relative to the other (which may be reversed in situs
      inversus), and the distribution of tissue within the hemisphere along the antero
      posterior axis ("volume torque"). RESULTS: Only volume torque was changed in
      schizophrenia-in comparison subjects, the coronal section of maximal left
      hemisphere volume was more anteriorly placed than on the right [and correlated
      with left superior temporal gyrus (STG) volume], and, in patients, it was more
      posterior (showing a reversed correlation with left STG volume). CONCLUSIONS: The
      findings validate a new approach to cerebral asymmetry. Assessments of cerebral
      asymmetry in psychosis should account for, or exclude, hemisphere shift, which is
      not changed, and focus on the second component, A-P volume distribution; the
      findings point to an anomaly of relative hemispheric development that may have
      pathophysiological significance.

PMID- 15721997
TI  - Symmetry of callosal information transfer in schizophrenia: a preliminary study.
AB  - OBJECTIVE: While there is much evidence to suggest left hemisphere dysfunction
      and interhemispheric transfer deficits in schizophrenia, the right hemisphere is
      rarely implicated. This study uses 128-channel EEG to assess whether asymmetry of
      interhemispheric transfer found in normal individuals is present in those with
      schizophrenia, and whether this might point to a right-hemisphere dysfunction.
      METHODS: Simple reaction time (RT) was recorded to stimuli presented to the left
      visual field (LVF), right visual field (RVF) or bilaterally (BVF) in 13 males
      with schizophrenia and 13 controls. 128-Channel EEG was simultaneously recorded.
      Interhemispheric transfer time (IHTT) in each direction was calculated by
      comparing the latencies of N160 EP components in the hemispheres contralateral
      and ipsilateral to stimulation. RESULTS: While controls showed faster information
      transfer from the right-to-left hemisphere, this asymmetry was not present in the
      schizophrenia group who also exhibited a concomitant decrease in the amplitude of
      the N160 in the right hemisphere. CONCLUSIONS: Results are interpreted with
      reference to a loss of rapidly conducting myelinated axons in the right
      hemisphere in schizophrenia.

PMID- 15721998
TI  - The effect of working memory performance on functional MRI in schizophrenia.
AB  - INTRODUCTION: Studies of prefrontal cortical (PFC) function in schizophrenia have
      been inconsistent, with studies showing both increased and decreased PFC
      activation compared to healthy controls. Discrepant findings may be due to task
      performance effects or demographic differences between samples. We report
      functional magnetic resonance imaging (fMRI) data comparing subjects with
      schizophrenia and healthy controls performing a 2-back working memory (WM) task,
      addressing the effects of task performance. METHODS: Twenty-two controls and 14
      patients with DSM-IV schizophrenia, scanned on a Siemens 1.5 T scanner, performed
      a visual letter 2-back task and control task (CPT-X) during fMRI. Data were
      analyzed using Statistical Parametric Mapping (SPM)-99. RESULTS: After
      statistical adjustment for performance differences, persons with schizophrenia
      showed significantly greater activation than controls in the right medial frontal
      gyrus and left inferior parietal lobule/medial temporal gyrus region (BA 39/40),
      and a trend toward greater activation in the left ventrolateral PFC. This pattern
      was also observed in demographically matched subgroups of participants.
      CONCLUSIONS: Data are consistent with findings reported in recent studies showing
      increased PFC and parietal activation in schizophrenia when the effects of
      reduced WM task performance in patients with schizophrenia are addressed. Further
      studies are needed to clarify the pathophysiological basis of WM load sensitivity
      in schizophrenia and its relationship to genes.

PMID- 15721999
TI  - Cognitive therapy for persistent psychosis in schizophrenia: a case-controlled
      clinical trial.
AB  - The results of an open label controlled outcome study are presented, comparing
      Cognitive Therapy with a treatment-as-usual group. Independent raters assessed
      symptom severity and psychosocial functioning at baseline, and again at 6 months.
      Improvements were found for Cognitive Behavior Therapy (CBT) patients in Clinical
      Global Impression for Improvement (CGI; p<0.03), Global Psychosocial Functioning
      (p<0.001), the Global Assessment Scale (GAS) ratings (p<0.013), overall symptoms
      (p<0.049), and delusions (p<0.029). A trend toward significance was found for
      reductions in negative symptoms (p<0.06). The results suggest the potential
      utility of cognitive therapy as a companion therapy for schizophrenia in the
      United States. Limitations of the study include small sample sizes, lack of
      randomized assignment, and rater nonblindedness to treatment condition.

PMID- 15722000
TI  - A pilot study of functional Cognitive Behavioral Therapy (fCBT) for
      schizophrenia.
AB  - BACKGROUND: The feasibility and preliminary efficacy of a novel cognitive
      behavioral treatment for decreasing psychotic symptoms and improving social
      functioning was evaluated in a pilot study. This represents the first treatment
      outcome study of CBT for psychosis with a manualized, active comparison
      condition. METHODS: Thirty outpatients with schizophrenia or schizoaffective
      disorder, depressed type with residual psychotic symptoms were randomly assigned
      to either 16 weekly sessions of functional cognitive behavioral therapy (fCBT) or
      psychoeducation (PE) with assessments conducted at baseline and post-treatment by
      blind evaluators. RESULTS: Attrition was only 7% and did not differ between fCBT
      and PE, indicating good tolerability of both treatments. For this sample with
      persistent symptoms, between groups effects were not significantly different, but
      within group effect sizes indicated greater treatment benefit for fCBT on
      positive symptoms, particularly for the PSYRATS voices subscale. CONCLUSION: The
      results suggest that fCBT is well tolerated and holds promise for reducing
      persistent positive symptoms.

PMID- 15722001
TI  - Insight into schizophrenia: the effects of cognitive behavioural therapy on the
      components of insight and association with sociodemographics--data on a
      previously published randomised controlled trial.
AB  - Insight in schizophrenia is an evolving concept with widespread use in clinical
      practice. Results are presented from a multicentre randomised trial in which
      patients with schizophrenia and carers received a short insight-focused Cognitive
      Behaviour Therapy (CBT) intervention from trained nurses in the community. The
      CBT group demonstrated significantly greater improvement in insight into
      compliance with treatment and the ability to re-label their psychotic symptoms as
      pathological compared with the control group at post-therapy assessment. Those
      participants who demonstrated improved insight into having a mental illness
      tended to become depressed. At the end of therapy and at 1-year follow-up, there
      was a statistically significantly increased dropout rate in African-Caribbean and
      Black African participants. The Black Caribbean group showed a significantly
      smaller change in insight compared to the white group. At 1-year follow-up, the
      result on total insight and compliance was durable. The change in insight in the
      Black African group was significantly lower compared to the white group. The
      study emphasizes the role of a short insight-focused CBT intervention in
      improving patients' insight into compliance and its implications. The results
      confirm previous findings of difficulties in engaging patients of Afro-Caribbean
      origin and their poor response to psychological therapies as currently delivered.

PMID- 15722002
TI  - Association of symptoms and executive function in schizophrenia and bipolar
      disorder.
AB  - The extent to which cognitive impairment in psychosis is related to the
      particular disorder or the pattern of symptoms is unclear. We examined executive
      function in two groups of schizophrenia patients with predominant symptoms of
      disorganisation (n=15) and psychomotor poverty (n=15), respectively, two groups
      of bipolar I disorder patients with predominant symptoms of mania (n=15) and
      depression (n=15), respectively, and 30 healthy controls. We predicted that the
      pattern of symptoms ('excess' [disorganisation/mania] or 'deficiency' [negative
      symptoms/depression]) would be more related to executive ability than the
      underlying disorder. The patient groups showed partially overlapping executive
      dysfunctions relative to the control group. There were no significant differences
      between groups with 'excess' symptoms (schizophrenia patients with thought
      disorder and bipolar patients with mania), or between groups with 'deficiency'
      symptoms (schizophrenia patients with negative symptoms and bipolar patients with
      depression). In contrast, differences were noted between groups with the same
      diagnosis: Schizophrenia patients with disorganisation were less accurate in
      semantic verbal fluency than those with negative symptoms; and bipolar patients
      with mania tended to be faster, but less accurate, in sentence completion than
      those with depression. A statistical comparison of the associations of
      'diagnosis' and the 'excess-deficiency' dimension with executive function
      revealed a trend for a greater association of the latter with two measures of
      performance accuracy. Executive dysfunction in patients with psychotic disorders
      may be more related to their symptom profile than their diagnosis.

PMID- 15722003
TI  - Cognitive and clinical moderators of recognition memory in schizophrenia: a meta
      analysis.
AB  - Recognition memory performance in schizophrenia has been shown to vary greatly
      across studies. To identify the conditions under which recognition memory is
      significantly impaired, we used a meta-analytic strategy to quantify the
      moderating effects of several cognitive and clinical variables. Eighty-four
      studies (from 1965 to July 2003) provided recognition memory data for both a
      schizophrenia and control group. The overall group comparison for recognition
      memory yielded a significant mean weighted effect size of d=0.76. Material
      specificity was the most significant cognitive variable found, with patients
      exhibiting greater impairment for figural than verbal recognition. A yes-no
      recognition format and auditory encoding also led to significantly greater effect
      sizes for recognition memory relative to forced-choice recognition tests and
      visual encoding, respectively. Furthermore, the effect size for recognition
      memory as measured by false alarm was smaller than the effect size as measured by
      hit rate or by d-prime and its related measures. Among clinical variables that
      were associated with higher effect sizes, chronicity was the most significant,
      but different trends linking poor performance to negative symptoms and general
      symptomatology were also observed. Thus, a recognition memory deficit moderated
      by both cognitive and clinical variables is clearly present in schizophrenia.

PMID- 15722004
TI  - The FOCIS international survey on psychiatrists' opinions on cognition in
      schizophrenia.
AB  - BACKGROUND: The goal of this project was to develop an interview to evaluate
      psychiatrists' views on the nature of cognitive dysfunction in schizophrenia, its
      importance as a potential treatment target, and its relative importance as a
      treatment target across different phases of schizophrenia. MATERIALS AND METHODS:
      A survey (available in paper or on-line) consisting of 27 questions, was
      developed by the Focus on Cognition in Schizophrenia (FOCIS) group, and
      distributed in a single wave mailing to 63,295 psychiatrists in 21 countries
      worldwide. RESULTS: The overall response rate was 4.7% (n=2975). The surveyed
      psychiatrists perceived cognition as a high treatment priority in stabilized
      schizophrenia patients, but less so for first episode or acute schizophrenia
      patients. The potential of atypical antipsychotics to improve cognitive
      dysfunction in schizophrenia was identified by 81% of the respondent
      psychiatrists. CONCLUSIONS: Cognitive deficits in people with schizophrenia are
      seen by clinical psychiatrists as relevant to treatment and rehabilitation plans.
      They were, however, regarded as a higher treatment priority in stabilized chronic
      rather than in first episode patients. The results suggest clinical psychiatrists
      need additional education regarding the nature of cognitive dysfunction in
      schizophrenia and its importance for psychosocial rehabilitation and community re
      entry.

PMID- 15722005
TI  - Decreased plasma brain-derived neurotrophic factor levels in schizophrenic
      patients with tardive dyskinesia: association with dyskinetic movements.
AB  - Neurodegenerative processes may be involved in the pathogenesis of tardive
      dyskinesia (TD). Accumulating evidence suggests that brain-derived neurotrophic
      factor (BDNF) plays a critical role in the maintenance of functional neurons. The
      present study was to examine plasma BDNF levels and the relationship among BDNF
      level, psychopathological and tardive dyskinesia symptoms in schizophrenic
      patients with TD. Eighty schizophrenic patients with TD were compared with 45
      schizophrenic patients without TD, as well as with 45 age-, sex-matched normal
      controls. The severity of TD was assessed using the Abnormal Involuntary Movement
      Scale (AIMS). The psychopathology of patients was assessed by the Positive and
      Negative Syndrome Scale (PANSS). Plasma BDNF levels were measured by sandwich
      enzyme-linked immunosorbent assay (ELISA). The results showed that the patients
      with TD had lower plasma BDNF levels than those without TD, and than that of
      normal controls. In the patients with TD, plasma BDNF levels was inversely
      correlated with AIMS total score, and with PANSS negative subscore. Female
      patients had significantly lower plasma BDNF levels than male TD patients. Our
      results suggest that decreased BDNF may play an important role in the
      pathophysiology of TD. There may be a relationship between decreased BDNF levels
      and dyskinetic movements associated with TD.

PMID- 15722007
TI  - Comorbid presentation of Kartagener's syndrome and schizophrenia: support of an
      etiologic hypothesis of anomalous development of cerebral asymmetry?

PMID- 15722006
TI  - Visual motion integration in schizophrenia patients, their first-degree
      relatives, and patients with bipolar disorder.
AB  - Many schizophrenia patients show degraded detection of coherent motion. This
      visual deficit may (1) be a consequence of having a specifically schizophrenic
      psychosis, (2) be a non-specific effect of suffering from a severe illness (i.e.,
      "generalized deficit"), or (3) reflect properties of the visual motion processing
      system that play an antecedent, possibly causal role in the pathophysiology of a
      disposition to schizophrenia. To distinguish among these possibilities, we
      measured the accuracy of detecting the direction of coherent motion in 29
      schizophrenia patients, 20 first-degree relatives of schizophrenia patients, 19
      patients with bipolar disorder and 33 normal controls. The task requires the
      integration of dynamic signals from stochastic random dot patterns in order to
      discern the direction of their motion. Schizophrenia patients, as a group, showed
      significantly elevated thresholds for detecting the direction of coherent motion,
      but relatives of schizophrenia patients and patients with bipolar disorder did
      not differ from normal controls on this task. The results indicate that visual
      motion integration, normally mediated in motion-sensitive brain areas such as the
      Middle Temporal Area, is impaired in patients with a clinically manifest
      schizophrenic psychosis, but is intact in patients with a non-schizophrenic
      psychosis (bipolar disorder) and in the relatives of schizophrenia patients. Our
      findings suggest that deficiencies in integrating motion signals, while specific
      for schizophrenia, do not seem to be a co-familial trait.

PMID- 15722009
TI  - From micro to nano: recent advances in high-resolution microscopy.
AB  - Improving the spatial resolution of optical microscopes is important for a vast
      number of applications in the life sciences. Optical microscopy allows intact
      samples and living cells to be studied in their natural environment, tasks that
      are not possible with other microscopy methods (e.g. electron microscopy). Major
      advances in the past two decades have significantly improved microscope
      resolution. By using interference and structured light methods microscope
      resolution has been improved to approximately 100 nm, and with non-linear methods
      a ten times improvement has been demonstrated to a current resolution limit of
      approximately 30 nm. These methods bring together old theoretical concepts such
      as interference with novel non-linear methods that improve spatial resolution
      beyond the limits that were previously assumed to be unreachable.

PMID- 15722010
TI  - Total internal reflection fluorescence microscopy: technical innovations and
      novel applications.
AB  - Recent years have seen the introduction of novel techniques and applications of
      total internal reflection fluorescence microscopy (TIRFM). Key technical
      achievements include miniaturization, enhanced depth resolution, reduction of
      detection volumes and the combination of TIRFM with other microscopic techniques.
      Novel applications have concentrated on single-molecule detection (e.g. of
      cellular receptors), imaging of exocytosis or endocytosis, measurements of
      adhesion foci of microtubules, and studies of the localization, activity and
      structural arrangement of specific ion channels. In addition to conventional
      fluorescent dyes, genetically engineered fluorescent proteins are increasingly
      being used to measure molecular conformations or intermolecular distances by
      fluorescence resonance energy transfer.

PMID- 15722011
TI  - Imaging protein molecules using FRET and FLIM microscopy.
AB  - Forster (or fluorescence) resonance energy transfer (FRET) and fluorescence
      lifetime imaging (FLIM) have moved center stage and are increasingly forming part
      of multifaceted imaging approaches. They are complementary methodologies that can
      be applied to advanced quantitative analyses. The widening application of FRET
      and FLIM has been driven by the availability of suitable fluorophores,
      increasingly sophisticated microscopy systems, methodologies to correct spectral
      bleed-through, and the ease with which FRET can be combined with other
      techniques. FRET and FLIM have recently found use in several applications: in the
      analysis of protein-protein interactions with high spatial and temporal
      specificity (e.g. clustering), in the study of conformational changes, in the
      analysis of binding sequences, and in applications such as high-throughput
      screening.

PMID- 15722012
TI  - Nucleocytoplasmic shuttling revealed by FRAP and FLIP technologies.
AB  - Protein mobility within cells is of key importance for many cellular functions.
      Although immunostaining can reveal protein locations in the steady-state, this
      might not represent the full picture and provides no information about protein
      movements. Fluorescence recovery after photobleaching (FRAP) and fluorescence
      loss in photobleaching (FLIP) are two techniques that enable the dynamics of
      intracellular protein mobility to be studied. These technologies have been
      successfully used to analyze the nucleocytoplasmic shuttling of STAT1, an
      intracellular signal transducer and activator of transcription, and can applied
      to the study of other proteins. Furthermore, FRAP and FLIP approaches have the
      added advantage of not affecting cell viability and might find application in the
      imaging of intracellular events in certain tissues and live animals.

PMID- 15722013
TI  - Site-specific labeling of proteins with small molecules in live cells.
AB  - The principal bottleneck for the utilization of small-molecule probes in live
      cells is the shortage of methodologies for targeting them with very high
      specificity to biological molecules or compartments of interest. Recently
      developed methods for labeling proteins with small-molecule probes in cells
      employ special protein or peptide handles that recruit small-molecule ligands,
      harness enzymes to catalyze small-molecule conjugation or hijack the cell's
      protein translation machinery.

PMID- 15722014
TI  - Image-based screening: a technology in transition.
AB  - Image-based screening (IBS) has proven itself with whole-well assays in which
      throughput and assay miniaturization are priorities. Recent interest, however,
      has centered upon the use of automated imaging technology to conduct assays at
      subcellular resolution. These in vitro assays have the potential to increase lead
      quality at early stages in drug discovery. Subcellular IBS is not yet mature and,
      although some assays provide reliable data at reasonable throughput, many others
      have yet to demonstrate robust application. Developments in image acquisition,
      analysis and informatics technologies are ongoing and are expected to broaden the
      usefulness of subcellular IBS.

PMID- 15722015
TI  - FISH and immunocytochemistry: towards visualising single target molecules in
      living cells.
AB  - Knowledge of how molecules interact in space and time is crucial for
      understanding cellular processes. A host of novel techniques have been developed
      for the visualisation of single target molecules in living cells, many based on
      fluorescence in situ hybridisation (FISH) or immunocytochemistry (IC). To extend
      the applicability of FISH to living cells, special backbone-modified probes and
      specific conformations (molecular beacons) have been designed. In the case of IC,
      conventional immunoreagents have been fine-tuned with respect to size and
      affinity or replaced with new protein scaffolds based on ankyrin repeat proteins.
      Other key advances include the use of proximity ligation to confirm vicinity
      binding and the use of quantum dots, which have proven potential for cellular
      labelling.

PMID- 15722016
TI  - Metal-enhanced fluorescence: an emerging tool in biotechnology.
AB  - Over the past 15 years, fluorescence has become the dominant detection/sensing
      technology in medical diagnostics and biotechnology. Although fluorescence is a
      highly sensitive technique, where single molecules can readily be detected, there
      is still a drive for reduced detection limits. The detection of a fluorophore is
      usually limited by its quantum yield, autofluorescence of the samples and/or the
      photostability of the fluorophores; however, there has been a recent explosion in
      the use of metallic nanostructures to favorably modify the spectral properties of
      fluorophores and to alleviate some of these fluorophore photophysical
      constraints. The use of fluorophore-metal interactions has been termed radiative
      decay engineering, metal-enhanced fluorescence or surface-enhanced fluorescence.

PMID- 15722017
TI  - In vivo molecular and cellular imaging with quantum dots.
AB  - Quantum dots (QDs), tiny light-emitting particles on the nanometer scale, are
      emerging as a new class of fluorescent probe for in vivo biomolecular and
      cellular imaging. In comparison with organic dyes and fluorescent proteins, QDs
      have unique optical and electronic properties: size-tunable light emission,
      improved signal brightness, resistance against photobleaching, and simultaneous
      excitation of multiple fluorescence colors. Recent advances have led to the
      development of multifunctional nanoparticle probes that are very bright and
      stable under complex in vivo conditions. A new structural design involves
      encapsulating luminescent QDs with amphiphilic block copolymers and linking the
      polymer coating to tumor-targeting ligands and drug delivery functionalities.
      Polymer-encapsulated QDs are essentially nontoxic to cells and animals, but their
      long-term in vivo toxicity and degradation need more careful study. Bioconjugated
      QDs have raised new possibilities for ultrasensitive and multiplexed imaging of
      molecular targets in living cells, animal models and possibly in humans.

PMID- 15722018
TI  - Bioluminescence imaging in living organisms.
AB  - Luciferase enzymes catalyze the emission of light from a substrate -- a
      phenomenon known as bioluminescence -- and have been employed as reporters of
      many biological functions. Luminescent reporters are much dimmer than fluorescent
      reporters, and therefore provide relatively modest spatial and temporal
      resolution. Yet, they are generally more sensitive and less toxic, making them
      particularly useful for long-term longitudinal studies of living cells, tissues
      and whole animals. Bioluminescence imaging has proven useful for detecting
      protein-protein interactions, for tracking cells in vivo, and for monitoring the
      transcriptional and post-transcriptional regulation of specific genes. Recent
      applications have included longitudinal monitoring of tumor progression in vivo,
      and monitoring circadian rhythms with single-cell resolution.

PMID- 15722019
TI  - Optical tomographic imaging of small animals.
AB  - Diffuse optical tomography is emerging as a viable new biomedical imaging
      modality. Using visible and near-infrared light this technique can probe the
      absorption and scattering properties of biological tissues. The main applications
      are currently in brain, breast, limb and joint imaging; however, optical
      tomographic imaging of small animals is attracting increasing attention. This
      interest is fuelled by recent advances in the transgenic manipulation of small
      animals that has led to many models of human disease. In addition, an ever
      increasing number of optically reactive biochemical markers has become available,
      which allow diseases to be detected at the molecular level long before
      macroscopic symptoms appear. The past three years have seen an array of novel
      technological developments that have led to the first optical tomographic studies
      of small animals in the areas of cerebral ischemia and cancer.

PMID- 15722020
TI  - Targeted contrast agents for magnetic resonance imaging and ultrasound.
AB  - The development of contrast agents that can be localized to a particular tissue
      or cellular epitope will potentially allow the noninvasive visualization and
      characterization of a variety of disease states. Recent advances have been made
      in the field of molecular imaging with magnetic resonance imaging and ultrasound
      and varied approaches have been devised to overcome the high background tissue
      signal. The types of agents and applications developed include gadolinium
      conjugated targeting molecules for imaging of fibrin, superparamagnetic iron
      oxide particles for stem-cell tracking, multimodal perfluorocarbon nanoparticles
      for visualization of angiogenesis, liposomes for targeting atheroma components,
      and microbubbles for imaging transplant rejection.

PMID- 15722021
TI  - Magnetic resonance microscopy: recent advances and applications.
AB  - Magnetic resonance microscopy is receiving increased attention as more
      researchers in the biological sciences are turning to non-invasive imaging to
      characterize development, perturbations, phenotypes and pathologies in model
      organisms ranging from amphibian embryos to adult rodents and even plants. The
      limits of spatial resolution are being explored as hardware improvements address
      the need for increased sensitivity. Recent developments include in vivo cell
      tracking, restricted diffusion imaging, functional magnetic resonance microscopy
      and three-dimensional mouse atlases. Important applications are also being
      developed outside biology in the fields of fluid mechanics, geology and
      chemistry.

PMID- 15722022
TI  - A glucose-sensing contact lens: from bench top to patient.
AB  - In the past few years we have seen the development of several new technologies
      for the continuous and non-invasive monitoring of physiological glucose, such as
      the GlucoWatch, glucose-sensing skin patches and approaches based on a glucose
      sensing tattoo. One approach that differs from current thinking is based on the
      determination and monitoring of tear glucose, which is well known to track blood
      glucose with an approximate 30 min lag time, using disposable and colorless
      contact lenses. These contact lenses can be worn by diabetics who can
      colorimetrically see changes in their contact lens color or other fluorescence
      based properties, giving an indication of tear and blood glucose levels.

PMID- 15722023
TI  - The natural history and laboratory diagnosis of human herpesviruses-6 and -7
      infections in the immunocompetent.
AB  - BACKGROUND: Human herpesviruses-6 and -7 (HHV-6/7) are widespread in all
      populations. In some individuals HHV-6 is found integrated into human
      chromosomes, which results in a high viral load in blood. HHV-6 variant B (HHV
      6B) and HHV-7 primary infections, although usually silent, not infrequently cause
      the childhood exanthem roseola infantum and are sometimes accompanied by
      neurological illness. HHV-6 variant A (HHV-6A) is not associated with any
      disease. OBJECTIVES: The present review focuses on the immunocompetent individual
      and considers the epidemiology of the two viruses and their role as human
      pathogens. It discusses the importance of satisfactory diagnostic tests to
      distinguish them, compares those currently available, and recommends how best to
      differentiate primary from persistent infection in each case. RESULTS: It is
      explained that at the present time antibody avidity immunofluorescence tests are
      the most reliable discriminators of the two types of infection. In primary
      infection these tests can be supplemented by PCR for viral DNA in blood but
      careful interpretation is required for HHV-6 in view of the high persistent viral
      DNA load seen with chromosomal integration. Since the contribution of primary HHV
      6 and -7 infections to the burden of severe neurological illness in young
      children is only now emerging as significant, the need to test for these viruses
      in such cases is stressed. CONCLUSIONS: 1. Primary HHV-6/7 infections must be
      distinguished from persistent infections. 2. Chromosomal integration of HHV-6
      requires urgent study. 3. HHV-6A/B must be distinguished in clinical situations.
      4. Where serious neurological disease/encephalitis is temporally related to
      immunisation it is particularly important to test for HHV-6/7 primary infection
      since otherwise the condition might wrongly be diagnosed as a vaccine reaction.
      5. Because less is currently known about HHV-7 and HHV-6A than HHV-6B, future
      studies should concentrate on the former two. 6. Improvements in diagnostic tests
      are required for each virus.

PMID- 15722024
TI  - Simultaneous infection with dengue 2 and 3 viruses in a Chinese patient return
      from Sri Lanka.
AB  - Dengue is an acute viral disease transmitted by the Aedes aegypti and Aedes
      albopictus mosquito, which are present in most tropical urban areas of the world.
      There are four antigenically distinct serotypes, designated dengue-1 (DEN-1),
      dengue-2 (DEN-2), dengue-3 (DEN-3) and dengue-4 (DEN-4). Dengue outbreaks have
      occurred in several regions in Asia, involving four serotypes of dengue 1, 2, 3
      and 4. In review of the few cases of dual infection documented in the literature,
      we report here a case of simultaneous infection with DEN-2 and DEN-3 in a Chinese
      patient return from Sri Lanka. The dual infection was identified by type-specific
      indirect immunofluorescence assay and confirmed by reverse transcriptase
      polymerase chain reaction (RT-PCR) and sequence determination. This is the first
      documented case of simultaneous infection with serotype of DEN-2 and DEN-3 in
      China.

PMID- 15722025
TI  - Phylogenetic analyses of human rotavirus in central Taiwan in 1996, 2001 and
      2002.
AB  - BACKGROUND: Rotavirus epidemiology information is required for gastroenteritis
      disease control and prevention. Information gathered about the serotype
      distribution of rotaviruses isolated in Taiwan is of crucial significance, before
      a licensed rotavirus vaccine is introduced. OBJECTIVES: The purpose of the
      present study is to investigate the epidemiological diversity of rotaviruses in
      Taiwan. STUDY DESIGN: A total of 51 stool samples taken from cases of acute
      gastroenteritis were collected from three teaching hospitals in central Taiwan in
      1996, 2001 and 2002. The samples were subjected to RT-PCR tests of VP7 gene of
      the human rotavirus group A, B, C. RESULTS: A total of 16 stool samples were
      detected positive by RT-PCR and 10 were sequence analyzed and classified into G1,
      G3, and G9 types. Compared with other HRV strains: the sequences of CS96-40 of G1
      are similar to MVD9816 (identity rate 97.15% and 96.09%, respectively, from
      Uruguay); the sequences of CS02-01 of G3 are similar to 98-B31 (identity rate
      98.93% and 98.72%, respectively, from Japan); the sequences of CS01-05, CS01-06,
      CS01-07, CS01-09, CS01-13, CS02-02, CS02-03, CS02-04 are very similar to other
      established G9 rotaviruses sequences (identity rate 96.85-99.88%), especially
      between CS02-04 and SP2737 (from Japan) with an identity rate of 99.88% and 100%
      nucleotide and amino acid, respectively. Except for CS01-06 strain, it is VR3,
      but not VR5, VR7 or VR8, that found to be the most frequent mutated amino acid
      regions of VP7 in these strains. CONCLUSIONS: Our findings are the first to
      document the high prevalence of G9 HRV strains in Taiwan, and suggest the re
      emergence of G3 strains in central Taiwan since 1991. Epidemiological surveys
      carried out in this study suggest genotype shifts from type G1 before 1996, to G9
      in 2001 and 2002 and the re-emergence of G3 type in 2002.

PMID- 15722026
TI  - Cytomegalovirus induces T-cell independent apoptosis in brain during
      immunodeficiency.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic viral pathogen
      associated with HIV/AIDS or immunosuppressive therapy. Systemic pathology may be
      caused either through direct virus-mediated infection or by indirect mechanisms
      such as 'by-stander' apoptosis. CMV infection of the central nervous system (CNS)
      occurs late in disease progression and understanding of pathology in the brain is
      fundamental for selection of appropriate therapies. OBJECTIVES: Using a model of
      disseminated neurotropic CMV disease, these experiments are designed to identify
      cellular predilection of murine CMV (MCMV) within mature brain and to determine,
      if CMV induces apoptosis within CNS cells. STUDY DESIGN: Adult immunodeficient
      (SCID) and normal BALB/c mice were infected via the tail vein with 4.5 x 10(5)pfu
      recombinant MCMV expressing a green fluorescent protein reporter. Animals were
      perfused at various time periods from 3 to 35 days post inoculation and tissues
      were stained for MCMV, GFAP, NEU-N, MBP, TUNEL, and caspase-3. RESULTS: CMV
      infection within brain was observed in multiple, independent foci affecting
      several different cell types, including neurons, glial cells, meninges, ependymal
      cells, and cerebral vessels. Cellular changes included nuclear karyopyknosis and
      karyorrhexis, and associated meningitis, choroiditis, encephalitis, vasculitis,
      and necrosis. TUNEL and caspase-3 staining of brain-demonstrated apoptosis of
      nearby 'by-stander' meningial, glial, and neuronal cells, but only in
      immunodeficient mice lacking T- and B-lymphocytes. Generally, only large CMV
      infection foci were associated with apoptosis of non-infected adjacent cells.
      CONCLUSIONS: These results indicate that MCMV may cause both direct and indirect
      pathology to brain and that T-cell independent apoptosis of surrounding cells of
      the CNS may be an important mechanism of disease in the pathogenesis of
      neurotropic CMV.

PMID- 15722027
TI  - A comparison of Thermo Electron RSV OIA to viral culture and direct fluorescent
      assay testing for respiratory syncytial virus.
AB  - BACKGROUND: Rapid diagnostic methods for respiratory syncytial virus are useful
      tools available for the clinician. OBJECTIVES: The Thermo Electron RSV OIA
      (optical immunoassay kit) was prospectively compared with direct
      immunofluorescent assay and viral culture at Primary Children's Medical Center,
      Salt Lake City, Utah. STUDY DESIGN: Specimens from three hundred and thirty
      patients exhibiting respiratory symptoms were collected for testing by the three
      methods above. Several specimens were positive by both OIA and DFA with a
      negative culture result. These culture results were verified by RT-PCR analysis.
      RESULTS: Overall, 107 specimens were positive for RSV by the reference tests
      (culture or RT-PCR). DFA analysis identified an additional 40 patient specimens
      positive for other respiratory viruses. Compared to the reference tests the
      sensitivity, specificity, positive, and negative predictive values of the OIA for
      detection of RSV were 87.9%, 99.6%, 98.9% and 94.5%, respectively. CONCLUSIONS:
      The rapid OIA assay format proved to be cost effective, and simple to use in
      comparison to DFA and viral culture. Negative rapid test results should still be
      confirmed with a secondary test.

PMID- 15722028
TI  - Establishment of conventional and fluorescence resonance energy transfer-based
      real-time PCR assays for detection of pathogenic New World arenaviruses.
AB  - BACKGROUND: Five of the known arenaviruses cause viral hemorrhagic fever in
      humans and are classified as biosafety level 4 pathogens. Four of the viruses,
      namely Junin, Guanarito, Machupo, and Sabia, belong to clade B of New World
      arenaviruses that also comprises the nonpathogenic viruses Tacaribe, Cupixi, and
      Amapari. OBJECTIVES: To establish real-time reverse transcription (RT)-PCR assays
      for Junin and Guanarito virus based on fluorescence resonance energy transfer
      (FRET) probes, and a universal RT-PCR assay for all known clade B viruses with
      conventional read-out. RESULTS: Conserved sequences in the nucleoprotein gene
      were chosen as target sites for primers and FRET probes. A common set of primers
      was designed for all three assays. The assays were based on one-step RT-PCR
      reagents and were optimised with respect to analytical sensitivity using
      synthetic RNA templates. The real-time PCR assays detected about 0.5 and
      5TCID(50) of cell culture-derived Junin and Guanarito virus, respectively. The
      universal clade B PCR amplified cell culture-derived RNA of Junin, Guanarito,
      Machupo, and Sabia virus (5-500TCID(50) per reaction), as well as RNA of
      Tacaribe, Cupixi, and Amapari virus. CONCLUSIONS: The PCR assays may be used as
      complementary diagnostic tests for pathogenic New World arenaviruses. The
      universal PCR assay could also be suitable for the detection of novel clade B
      arenaviruses in patients as well as in animal reservoirs.

PMID- 15722029
TI  - Detection of enterovirus RNA in cerebrospinal fluid (CSF) using NucliSens EasyQ
      Enterovirus assay.
AB  - Rapid detection of enterovirus (EV) infections is essential in the management of
      aseptic meningitis. Molecular approaches have opened the way to such rapid, but
      also specific and sensitive, diagnostic tests. The aim of this study was to
      compare the performance of the CE marked NucliSens EasyQ Enterovirus assay with
      an in-house two-step RT-PCR assay using cerebrospinal fluid (CSF) and throat swab
      samples. In addition, specificity was tested with clinical isolates positive for
      viruses with clinical importance in CSF samples. For nucleic acid extraction, the
      NucliSens miniMAG and NucliSens magnetic extraction reagents were used.
      Subsequently real-time nucleic acid sequence-based amplification (NASBA) RNA
      amplification was performed using NucliSens EasyQ basic kit reagents and
      NucliSens EasyQ Enterovirus reagents. An EV-specific internal homologous control
      (IC) RNA was used to monitor the entire NucliSens EasyQ procedure at the
      individual sample level. No IC but an external inhibition control was available
      for the RT-PCR method. For the NucliSens EasyQ procedure, amplification and real
      time detection reactions were carried out in the NucliSens EasyQ analyzer. The
      real-time NASBA enterovirus detection was based on NASBA amplification and real
      time molecular beacon technology. Data were analyzed using the manufacturer's
      software on the NucliSens EasyQ analyzer. For the in-house assay, RT-PCR
      amplicons were detected using agarose gel analysis. The analysis of clinical
      samples positive for HSV-1, HSV-2, adenovirus, CMV, VZV, mumps and rhinovirus
      were all negative by NucliSens EasyQ Enterovirus assay. Three rhinovirus samples
      were, however, strongly positive in RT-PCR. A total of 141 clinical samples were
      retrospectively tested, including 126 cerebrospinal fluid (CSF) samples and 15
      throat swabs. The 91 CSF samples were negative by both methods, 31 CSF samples
      and 14 throat swab samples were positive by both methods. The four CSF samples
      were positive by RT-PCR only. One throat swab sample was negative in NucliSens
      EasyQ but positive in RT-PCR. The sensitivity and specificity of both methods
      seem to be more or less comparable. However, the in-house RT-PCR assay appears to
      amplify some rhinovirus strains and should therefore not be used for throat swab
      samples. NucliSens EasyQ Enterovirus assay gave more invalid results than the in
      house RT-PCR, which is obvious taken into account the difference in quality
      control between the CE marked NucliSens EasyQ Enterovirus assay and the in-house
      enterovirus assay. The NucliSens EasyQ procedure can be completed within 5h
      versus 9.5h for the RT-PCR. NucliSens EasyQ Enterovirus assay showed to be a
      standardized, rapid, specific, sensitive and reliable procedure for the detection
      of enterovirus RNA.

PMID- 15722031
TI  - Splenic infarction due to transient antiphospholipid antibodies induced by acute
      Epstein-Barr virus infection.
AB  - Splenic infarction is a rare feature of infectious mononucleosis (IM) due to
      Epstein-Barr virus (EBV), limited to three case reports. We report the first case
      of splenic infarction during acute EBV infection associated with the transient
      induction of antiphospholipid antibodies. We discuss the role of antiphospholipid
      antibodies in thrombosis in acute viral infections and postulate other mechanisms
      of thrombosis. Once other more common causes of splenic infarction, such as
      endocarditis and lymphoma, have been excluded, the possibility of viral-induced
      antiphospholipid antibodies should be considered.

PMID- 15722030
TI  - Selection of a rare resistance profile in an HIV-1-infected patient exhibiting a
      failure to an antiretroviral regimen including tenofovir DF.
AB  - The human immunodeficiency virus type 1 (HIV-1) resistance profile, K65R, K70E
      and M184V, on reverse transcriptase gene was associated with the virologic
      rebound consecutively to the switch of lopinavir/r to tenofovir DF in a stable
      regimen with nucleoside backbone of abacavir, lamivudine and didanosine. The high
      selective pressure on the same resistance pathway was probably associated with
      the loss of antiviral potency, even in well-controlled patient.

PMID- 15722033
TI  - Human cytomegalovirus (HCMV) short tandem repeats analysis in congenital
      infection.

PMID- 15722032
TI  - Natural resistance-associated mutations to Enfuvirtide (T20) and polymorphisms in
      the gp41 region of different HIV-1 genetic forms from T20 naive patients.
AB  - BACKGROUND: The natural occurrence of primary resistance mutations in reverse
      transcriptase (RT) and protease (PR) genes of HIV-1 isolates from untreated
      patients has been reported and it may have important implications for the
      response to drug treatment. It is predictable that the same occurs in the HR1
      region of gp41 sequence from patients who have never received T20 therapy, and in
      this regard it would be important to know not only the mutation frequencies at
      HR1 region but also the natural polymorphisms at resistance-associated positions
      present in the absence of this drug. OBJECTIVES: The objectives of this study are
      to investigate the existence of natural resistance-associated mutations to T20 in
      HR1 gp41 region corresponding to different HIV-1 genetic forms from T20 naive
      patients and to determine their prevalence. STUDY DESIGN: Two hundred HIV-1 gp41
      sequences were included: subtype B: 164 (81.3%); subtype A: 15 (8.2%); subtype G:
      10 (4.6%); subtype F: 6 (3.5%); subtype C: 3 (1.8%); subtype K: 1 (0.6%); and
      subtype D: 1 (0.6%). We analyzed the resistance-associated mutations previously
      described: Q32H/R, G36D/S, I37V, V38A/M, Q39R/H, Q40H, N42T/D/Q/H, N43D/S/K/Q,
      L44M, L45M, R46M and V69I. RESULTS: Natural resistance mutations to T20 were
      found at a high frequency: 10.5%, corresponding to 9.1% in subtype B and 16.7% in
      non-B subtype samples. Polymorphisms were more frequent in non-B and recombinant
      forms than in subtype B (p<0.001). Different substitutions were related to
      subtypes: N42S in subtypes A, B, G and C, but not in F, Q56R in subtype A from
      CRF02_AG, and L54M in subtype B from CRF14_BG. CONCLUSIONS: To our knowledge this
      is the first study describing natural-resistance to T20 among different HIV-1
      subtypes, warranting a study of the biological significance of this mutations and
      their clinical relevance. The detection of differences between subtypes may have
      an influence on the rate and patterns of resistance in patients undergoing T20
      treatment.

PMID- 15722034
TI  - Trends of HIV-1 molecular epidemiology in Venezuela: introduction of subtype C
      and identification of a novel B/C mosaic genome.

PMID- 15722035
TI  - From nanoseparations to macropurifications. Proceedings of the 9th International
      Symposium on Biochromatography. Bordeaux, France, 5-7 May 2004.

PMID- 15722037
TI  - Adsorptive purification of pDNA on superporous rigid cross-linked cellulose
      matrix.
AB  - Use of plasmid DNA (pDNA) in the emerging gene therapy requires pure DNA in large
      quantities requiring production of safe DNA on large scale. While a number of kit
      based DNA purification techniques have become popular, large scale cost effective
      purification of DNA remains a technological challenge. Most traditional, as well
      as newly developed methods for DNA purification are expensive, tedious, use toxic
      reagents, and/or generally not amenable for scaled up production. Our attempts to
      develop a scalable adsorptive separation technology resulted in successful use of
      indigenously developed rigid cross-linked cellulose beads for single step
      purification of pDNA from alkaline cell lysates. This mode of purification
      employs a combination of intra-particle interactions that could give a product
      plasmid DNA free from chromosomal DNA, RNA and host proteins in a single scalable
      chromatographic step. The technology can be employed as a batch adsorption step
      on small scale, or on a large scale column chromatography. A high copy number 9.8
      kb plasmid (from an Escherichia coli strain) was purified in yields of 77 and
      52%, respectively in batch and column modes. The product obtained was homogeneous
      supercoiled plasmid with no RNA and protein contamination confirmed by
      quantitative analysis, agarose gel electrophoresis and SDS-PAGE.

PMID- 15722038
TI  - Preparative parallel protein purification (P4).
AB  - In state of the art drug discovery, it is essential to gain structural
      information of pharmacologically relevant proteins. Increasing the output of
      novel protein structures requires improved preparative methods for high
      throughput (HT) protein purification. Currently, most HT platforms are limited to
      small-scale and available technology for increasing throughput at larger scales
      is scarce. We have adapted a 10-channel parallel flash chromatography system for
      protein purification applications. The system enables us to perform 10 different
      purifications in parallel with individual gradients and UV monitoring. Typical
      protein purification applications were set up. Methods for ion exchange
      chromatography were developed for different sample proteins and columns. Affinity
      chromatography was optimized for His-tagged proteins using metal chelating media
      and buffer exchange by gel filtration was also tested. The results from the
      present system were comparable, with respect to resolution and reproducibility,
      with those from control experiments on an AKTA purifier system. Finally, lysates
      from 10 E. coli cultures expressing different His-tagged proteins were subjected
      to a three-step parallel purification procedure, combining the above-mentioned
      procedures. Nine proteins were successfully purified whereas one failed probably
      due to lack of expression.

PMID- 15722039
TI  - LdARL-1 His-tagged recombinant protein: purification by immobilized metal
      affinity expanded bed adsorption.
AB  - Previously we have cloned three ADP-ribosylation factor-like (ARL) genes from the
      parasitic protozoan Leishmania donovani: LdARL-3A and 3B, LdARL-1. LdARL-3A was
      previously purified as an active native form, which was able to bind GTP in
      vitro. In this paper, we have performed the production and the purification of
      Histidine-tagged (His-tagged) LdARL-1 recombinant protein by immobilized metal
      affinity chromatography (IMAC) using expanded bed adsorption (EBA) technology.
      This protein was purified with more than 95% purity and could be successfully
      used for GTP-binding assay.

PMID- 15722040
TI  - Purification and on-column refolding of EGFP overexpressed as inclusion bodies in
      Escherichia coli with expanded bed anion exchange chromatography.
AB  - The enhanced green fluorescent protein (EGFP) was over-expressed in Escherichia
      coli as inclusion bodies to increase its quantity and to facilitate its
      purification. Insoluble EGFP has been purified on Q Hyper Z matrix by expanded
      bed adsorption after solubilization in 8 M urea. The adsorption was made in
      expanded bed mode to avoid centrifugation. EBA-column refolding was done by
      elimination of urea and elution with NaCl. The EGFP was obtained as a highly
      purified soluble form with similar behavior in fluorescence and electrophoresis
      as native EGFP.

PMID- 15722041
TI  - Single step purification of a series of wheat recombinant proteins with expanded
      bed absorption chromatography.
AB  - Expanded bed absorption chromatography (EBA) was used to improve and simplify the
      purification of several wheat recombinant proteins. Binding and elution
      conditions were set to allow the purification of the over expressed protein in a
      single step. In comparison with our previous multi step protocol, same purity was
      obtained while EBA required less time (one day instead of five) and gave a higher
      yield (63% instead of 10%). This new procedure was then used for the successful
      purification of five other wheat ns-LTP. Despite their important polymorphism
      (identity from 44 to 97 %-pHi from 8 to 10), the EBA protocol allowed their
      purification in a single step.

PMID- 15722042
TI  - Large scale purification of rapeseed proteins (Brassica napus L.).
AB  - Rapeseed (Brassica napus L.) cruciferin (12S globulin), napin (2S albumin) and
      lipid transfer proteins (LTP) were purified at a multi-g scale. The procedure
      developed was simple, rather fast and resolutive; it permitted the recovery of
      these proteins with a good yield, such as 40% for cruciferin and 18% for napin.
      Nanofiltration eliminated the major phenolic compounds. The remaining protein
      fraction was fractionated by cation exchange chromatography (CEC) on a streamline
      SP-XL column in alkaline conditions. The unbound neutral cruciferin was polished
      by size exclusion chromatography. The alkaline napin isoforms and LTP, adsorbed
      on the beads, were eluted as a whole fraction and further separated by an other
      CEC step at acidic pH. Napins were polished by hydrophobic interaction
      chromatography (HIC). The fractions were characterized by reverse phase HPLC,
      electrophoresis, N-terminal sequencing and mass spectrometry. All the fractions
      contained less than 5% of impurities.

PMID- 15722043
TI  - Improvement in production and purification bioprocesses of bacterially expressed
      anti-alphaIIbbeta3 human single-chain FV antibodies.
AB  - Production of anti-alphaIIbbeta3 (anti-alphaIIbbeta3)-binding single-chain FV
      (scFv) fragments obtained from combinatorial libraries of IgG human antibodies is
      of broad interest for imaging and treatment of acute coronary syndromes. The
      objective of our work was to design an optimized production of one selected anti
      alphaIIbbeta3-binding scFv fragment for subsequent in vivo animal studies. Fed
      batch fermentation was initiated with 2TY media supplemented with 0.1 M glucose.
      This growing batch culture was used as a starting point for further fed-batch
      induction, in which a media without glucose containing 1 mM IPTG and 0.4 M
      saccharose was continuously added. Subsequent purification was performed on the
      whole cell extract in native conditions over an immobilized copper-ion affinity
      column. The improved conditions allowed the recovery of 5 mg of highly purified
      scFv fragments as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The bioactivity of the scFv fragments was further
      monitored by ELISA, cytometric and immunohistochemical methods.

PMID- 15722044
TI  - Purification of IgG and insulin on supports grafted by sialic acid developing
      "thiophilic-like" interactions.
AB  - We developed the synthesis of new supports for the purification of insulin and
      IgG by affinity chromatography. The preparation of such an affinity support is
      performed in two steps. First, silica beads are coated with dextran polymers
      carrying a calculated amount of positively charged diethylaminoethyl groups in
      order to mask negative charges at its surface. Second, ligand is immobilized
      using a coupling agent. This support combines the advantages of polysaccharide
      phases with the excellent mechanical characteristics of silica. The existence of
      N-acetylneuraminic acid (sialic acid) in insulin receptor and in the antigenic
      determinant of IgG suggests that such an acid may develop specific interactions
      usable in affinity chromatography. Therefore, N-acetylneuraminic acid was used as
      an active ligand. The immobilization of sialic acid can be carried out by using
      the conventional coupling agent: the carbonyldiimidazole. The performances of
      these supports grafted by sialic acid were studied by high-performance liquid
      affinity chromatography (HPAC). The optimization of the chromatographic
      conditions (support characteristics and mobile phase) enabled us to observe a
      behavior of the type "thiophilic" of the support, which does not contain sulfone
      group. This new affinity support allowed a one-step separation of the IgG from
      mouse ascitic fluids and also allowed the insulin purification from a pancreatic
      extract with a good purification yields.

PMID- 15722045
TI  - Capture of a monoclonal antibody and prediction of separation conditions using a
      synthetic multimodal ligand attached on chips and beads.
AB  - A synthetic ligand called 2-mercapto-5-benzimidazolesulfonic acid has been
      successfully used for the specific chromatographic capture of antibodies from a
      cell culture supernatant. Adsorption occurred at physiological ionic strength and
      pH range between 5.0 and 6.0, with some binding capacity variations within this
      pH range: antibody uptake increased when the pH decreased. With very dilute
      feedstocks, as was the case with the cell culture supernatant under
      investigation, it was found that the pH had to be slightly lowered to get a good
      antibody sorption capacity. To optimize separation conditions, a preliminary
      study was made using ProteinChip Arrays that displayed the same chemical
      functionalities as the resin. Arrays were analyzed using SELDI-MS. By this mean,
      it was possible to cross-over simultaneously different pH conditions at the
      adsorption and the desorption steps. Best conditions were implemented for
      preparative separation using regular lab-scale columns. At pH 5.2, antibody
      adsorption was not complete, while at pH 5.0 the antibody was entirely captured.
      pH 9 was selected at elution, rather than pH 8.0 or 10.0, and resulted in a
      complete desorption of antibodies from the column. Benefits of the prediction of
      separation conditions of antibodies on MBI beads using SELDI-MS were a
      significant reduction in analysis time and in sample volume. This was possible
      because the separation of IgG on the chip surface did mimic very well the
      separation on beads.

PMID- 15722046
TI  - Isolation of fibronectin type III like peptide from human placental extract used
      as wound healer.
AB  - A peptide of around 7.4 kDa has been purified from the aqueous extract of human
      placenta used as wound healer. Derived partial amino acid sequence from mass
      spectrometric analysis showed its homology with human fibronectin type III. Under
      nondenaturing condition, it formed aggregate, the elution pattern of which from
      reverse-phase HPLC was identical with that of fibronectin type III. Immuno-blot
      of the peptide with reference fibronectin type III-C showed strong cross
      reactivity. Since fibronectin type III plays important roles in wound healing,
      similar peptide in the extract is likely to take part in curing process.

PMID- 15722047
TI  - Copper binding to prion octarepeat peptides, a combined metal chelate affinity
      and immunochemical approaches.
AB  - Based on the hypothetical proposal of Sulkowski [E. Sulkowski, FEBS Lett. 307 (2)
      (1992) 129] for the implication of transition metal ions in the structural
      changes/oligomerisation of normal cellular prion protein (PrPc) resulting in the
      pathological isoform (PrPsc), we focused our study on the octarepat domain of
      this protein which has been supposed to be the metal binding site. We have
      studied the copper binding to synthetic prion octarepeat peptides (PHGGGWGQ)n
      (n=1, 3, 6) using metal chelate and size-exclusion modes of chromatographies.
      This copper binding induces oligomerisation resulting in multiple aggregates.
      Moreover, heterogeneity of metal bound octarepeat oligomers by ESI-MS has been
      demonstrated. In addition, anti prion antibodies specific to the octarepeat
      region were used to discriminate between metal free and copper, nickel and zinc
      bound hexamer octarepeat peptide. Differential recognition of Cu(II) and Zn(II)
      bound complexes has been observed which signify differences in exposed epitopes
      of aggregated peptides.

PMID- 15722048
TI  - One step flow-through adsorptive purification of tubulin from tissue homogenate.
AB  - Tubulin, a potential target for anti-cancer drugs, has been purified in one step
      and obtained as flow-through fraction directly from an extract of a mammalian
      brain tissue by adsorption chromatography on H-CELBEADS, an indigenously
      developed rigid, superporous cross-linked cellulose based weakly hydrophobic
      adsorbent. The fibrous polymerized tubulin mass passed through the H-CELBEADS bed
      while the associated proteins were separated by adsorption. The final tubulin
      preparation was obtained free from other proteins as seen on SDS-PAGE. Purified
      tubulin was obtained in a yield of about 29 mg/100 g brain, and its bioactivity,
      evaluated through its ability to bind colchicine, was found to be preserved.

PMID- 15722049
TI  - The use of confocal laser scanning microscopy to study the transport of
      biomacromolecules in a macroporous support.
AB  - Large-pore materials or supports resembling polymer conduits are used as packing
      material in chromatographic operations. Our ongoing research has shown that, when
      modified with peptides or ligands, chitosan beads that are 800 microm in diameter
      and have 3.5% solids can be used as matrices in bioseparations. The goal of the
      present study is to evaluate the transport properties of biomolecules in the
      modified chitosan beaded matrices. Batch uptake experiments with fluorescently
      tagged pure human IgG, human IgA and human IgM were conducted to visualize the
      distribution of binding sites throughout the bead as well as to evaluate
      restrictions to diffusion, if any, within the support. The chromatographic
      performance of the macrobeads was first assessed by the classical height
      equivalent of a theoretical plate HETP analysis. The independence of HETP on
      linear flow rates studied suggests that a likely mode of solute transport within
      the macrobeads may be a combination of convection and diffusion-convective
      components. By using fluorescent-tagged immunoglobulins, the penetration of the
      adsorbent particle at different times and different levels of saturation was
      visually observed. The profiles obtained from dynamic experiments were compared
      to the profiles obtained from finite bath experiments. With an increase in the
      incubation time, the degree of penetration increased and the bead interior was
      saturated with FITC immunoglobulins at the end point of the finite bath
      experiment. In the dynamic uptake experiment, the degree of penetration was found
      to be a function of the linear velocity and level of breakthrough. The
      penetration of the bead radius, at times lower than the predicted diffusion time,
      suggests that the mode of transport in the chitosan beads is governed by a
      combination of convective and diffusive forces.

PMID- 15722050
TI  - Carrier ampholytes as potential buffers in electrophoresis: physico-chemical
      study.
AB  - Joule heating is a limiting factor when separating proteins in capillary zone
      electrophoresis (CZE). Low conductivity buffers, are required for high-speed
      separations. We investigated the use of carrier ampholytes (CA) as background
      electrolytes (BGE) in CZE. We prepared 25 "narrow pH cuts" of wide pH range (3
      10) CA mixture in order to know if these fractions were suitable to be used as
      BGE in CZE. Each fraction was characterised by CZE analysis, giving an idea of
      its heterogeneity (number and relative abundance of molecular ampholytes).
      Conductivities and buffering capacities of each fraction have been also measured.
      Our conclusion is that "narrow pH cuts" of CA might be well suited buffers for
      electrophoretic separations.

PMID- 15722051
TI  - Kainic acid induces rapid cell death followed by transiently reduced cell
      proliferation in the immature granule cell layer of rat organotypic hippocampal
      slice cultures.
AB  - Brain injury due to seizures results in transiently increased cell proliferation
      and neurogenesis in the subgranular zone of the adult dentate gyrus. In contrast,
      the immature postnatal brain appears to be more resistant to cell death after
      seizure-induced brain injury and paradoxically reacts to seizures by reducing SGZ
      proliferation. Organotypic hippocampal slice cultures are a useful paradigm for
      modelling the early postnatal hippocampus. We have investigated the temporal
      relationship between cell death and cell proliferation after kainate in the
      granule cell layer of rat organotypic hippocampal slice cultures equivalent to
      post natal day 11 animals. We found stable numbers and densities of mature
      thionine stained cells in the granule cell layer over 72 h in control cultures
      grown in defined medium. We also found a slowly declining cell proliferation rate
      over the same time period under control conditions. We report evidence of early
      cell death in the granule cell layer after just 2 h exposure to 5 microM kainate,
      followed by a significant decrease in cell proliferation in the granule cell
      layer at 24 h. In contrast to control conditions, cell proliferation rose
      significantly in the kainate exposed cultures by 72 h back to levels seen at 2 h.
      There were no significant changes in cell labelling with antibody to activated
      caspase-3 between kainate treated and control cultures at any time point
      examined. Our results suggest that kainate-induced injury in the early postnatal
      hippocampus damages precursor cells contributing to a reduction in granule layer
      cell proliferation.

PMID- 15722052
TI  - The effects of amygdala lesions on hippocampal activity and classical eyeblink
      conditioning in rats.
AB  - The hippocampus and the amygdala have long been associated with memory, emotion,
      and motivated behaviors. Although the role of these two brain areas in learning a
      simple, discrete motor response has been well studied, a definitive theory
      concerning their functions remains elusive. The present experiment involved
      selective lesions of the central nucleus (CE) or the basolateral nucleus (BA) of
      the amygdala in rats followed by single-unit analyses of hippocampal CA1 subfield
      activity during classical eye blink conditioning. Removal of CE or BA adversely
      affected the development of conditioned responding. Differences between groups in
      the patterns of hippocampal activity were observed. Similar to previous rabbit
      studies, hippocampal activity recorded from sham rats showed that CA1 cells
      became active during the CS-US period as conditioning progressed with activity
      especially prevalent just prior to US onset. Increased activity over training was
      seen during the CS-US interval in CE-lesioned rats, but the pattern differed from
      control rats-uniform excitation was seen across the entire CS-US period. BA
      lesioned rats initially showed uniform CS-US period activation in early phases of
      training, but then showed patterns of hippocampal activity that resembled control
      rats in later stages of conditioning. The data suggest that the amygdala may play
      a modulatory role in the acquisition of conditioned eye blink responses and also
      in the formation of learning-related activity in the hippocampus.

PMID- 15722053
TI  - Repeated cocaine exposure during adolescence alters glutamic acid decarboxylase
      65 (GAD65) immunoreactivity in hamster brain: correlation with offensive
      aggression.
AB  - Male Syrian hamsters (Mesocricetus auratus) treated with low-dose (0.5 mg/kg/day)
      cocaine throughout adolescence (P27-P56) display highly escalated offensive
      aggression. The current study examined whether adolescent cocaine exposure
      influenced the immunohistochemical localization of glutamic acid decarboxylase-65
      (GAD65), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid
      (GABA), a fast-acting neurotransmitter implicated in the modulation of aggression
      in various species and models of aggression. Hamsters were administered low doses
      of cocaine throughout adolescence, scored for offensive aggression using the
      resident-intruder paradigm, and then examined for changes in GAD65
      immunoreactivity in areas of the brain implicated in aggression control. When
      compared with saline-treated control animals, aggressive cocaine-treated hamsters
      showed significant differences in the area covered by GAD65 puncta in several
      notable aggression regions, including the anterior hypothalamus, the medial and
      central amygdaloid nuclei, and the lateral septum. However, no differences in
      GAD65 puncta were found in other aggression areas, such as the bed nucleus of the
      stria terminalis, the ventrolateral hypothalamus, and the corticomedial amygdala.
      Together, these results suggest that altered GABA synthesis and function in
      specific aggression areas may be involved in adolescent cocaine-facilitated
      offensive aggression.

PMID- 15722054
TI  - Distribution in brain of liposomes after convection enhanced delivery; modulation
      by particle charge, particle diameter, and presence of steric coating.
AB  - We have investigated the role of diameter, charge, and steric shielding on the
      brain distribution of liposomes infused by convection enhanced delivery (CED)
      using both radiolabeled and fluorescent-labeled particles. Liposomes of 40 and 80
      nm diameter traveled the same distance but penetrated significantly less than a
      10-kDa dextran; whereas 200-nm-diameter liposomes penetrated less than 80 nm
      liposomes. A neutral liposome shielded by polyethylene glycol (PEG; 2 kDa; 10% by
      mole) penetrated significantly farther than an unshielded liposome. Even when
      shielded with PEG, positive surface charge (10% by mole) significantly reduced
      the penetration radius compared to a neutral or negative charged liposome (10% by
      mole). A mathematical CED model including a term for liposome cell binding was
      applied to analyze the radius of particle penetration. Neutral liposomes had a
      binding constant of k=0.0010+/-0.0002 min-1, whereas for positive charged
      liposomes k increased 50-fold. The binding constant was independently verified
      using a degradable lipid radiolabel that eliminated from the brain with a 9.9+/
      2.0 h half-life, equivalent to the calculated elimination constant k=0.0012+/
      0.0002 min-1. During CED, liposomes accumulated in a subpopulation of
      perivascular cells within the brain. A non-degradable lipid radiolabel showed
      that lipid components remained within these perivascular brain cells for at least
      2 days. To reduce this uptake, 100-fold molar excess of non-labeled liposomes
      were co-infused with labeled liposomes, which significantly increased liposome
      penetration. These studies suggest that optimization of therapeutic CED using
      particles such as drug-loaded liposomes, polymeric nanoparticles, non-viral DNA
      complexes, and viruses will require a strategy to overcome particle binding and
      clearance by cells within the CNS.

PMID- 15722055
TI  - Behavioral effects of 8-OH-DPAT injections into pontine and mesencephalic areas
      containing 5-HT-immunoreactive perikarya in the pigeon.
AB  - This study examined the distribution of 5-HT-immunoreactive perikarya (5-HT-IRp)
      and the effects of local injections of 8-OH-DPAT into 5-HT-IRp-containing pontine
      and mesencephalic regions on feeding and drinking behaviors in free-feeding
      pigeons. When infused into the midline 5-HT-IRp-containing areas, 8-OH-DPAT (6.1
      nmol) reliably elicited drinking and, to a lesser extent, feeding responses
      during the first hour after injection. These responses were significantly higher
      than the ingestive indexes observed (1) after vehicle (ascorbic acid 0.1%, 200
      nl) injections at the same sites and (2) after 8-OH-DPAT injections into adjacent
      sites devoid of 5-HT-IRp. Increases in drinking were proportionally higher than
      those observed in feeding and a significant negative correlation was observed
      between water and food after midline 8-OH-DPAT injections. Similar dipsogenic
      responses were observed after injections of different 8-OH-DPAT doses (0.6, 2.0,
      and 6.1 nmol). Pretreatment with local injections of p-MPPI (an antagonist of 5
      HT1A receptors) attenuated the ingestive responses evoked by 8-OH-DPAT
      injections. Injections of 8-OH-DPAT into lateral 5-HT-IRp-containing sites evoked
      only inconsistent and weak ingestive responses. These results indicate that 5
      HT1A receptor-mediated circuits located in the midline superior raphe system of
      the pigeon may play an important role in mechanisms controlling water intake,
      similar to that observed in mammals.

PMID- 15722056
TI  - Hemisphere-specific effects on serotonin but not dopamine innervation in the
      nucleus accumbens of gerbils caused by isolated rearing and a single early
      methamphetamine challenge.
AB  - The aim of this study was twofold: We examined whether serotonin (5-HT) and
      dopamine (DA) innervations of the nucleus accumbens are lateralised and whether
      the environment or the combination with an early pharmacological impact might
      interfere with the postnatal maturation of the monoaminergic innervation. Male
      gerbils were assigned to either enriched rearing (ER) or isolated rearing (IR).
      Animals from both rearing conditions additionally received a single dose of
      either methamphetamine [MA (50 mg/kg ip)] or saline on postnatal day 14. DA and 5
      HT fibres of the adult animals (postnatal day 90-110) were immunocytochemically
      stained and fibre densities were quantified in nucleus accumbens core and shell
      of both the left and right hemisphere. Our data demonstrate that the DA and 5-HT
      innervation is not lateralised in saline-treated animals of both rearing
      conditions. IR increases the DA fibre density in both hemispheres of saline
      controls, whereas an additional MA treatment reverses this effect. In both ER and
      IR groups, MA provokes an excessive 5-HT fibre in growth of only the right
      hemisphere. The combination of IR with MA induces right-side asymmetries of the 5
      HT fibre density in both the core and shell. From the data obtained, we conclude
      that the maturation of the monoaminergic innervation of the nucleus accumbens is
      vulnerable to postnatal stimuli. The subtle "innervation imbalance" observed in
      our studies is consistent with previously reported effects in other brain regions
      of this animal model and may be causative for behavioural disturbances.

PMID- 15722057
TI  - NMDA receptor stimulation in the absence of extracellular Ca2+ potentiates Ca2+
      influx-dependent cell death system.
AB  - The meaning of Ca2+ influx in the time course of glutamate stimulation of
      neuronal cells was addressed. We demonstrated that Ca2+ influx did not work
      straightforward in the determination of the fate of neuronal cells. There appears
      to be a critical period for Ca2+ influx to work efficiently in glutamate-induced
      neuronal cell death. When Ca2+ influx for 5 min from the beginning of glutamate
      stimulation was allowed in the whole stimulation period for 15 min, potent
      neuronal cell death could not be attained. On the other hand, when neuronal cells
      had been pre-treated with glutamate or NMDA for 5-10 min in the absence of
      extracellular Ca2+ following Ca2+ influx for 5 min fully induced neuronal cell
      death. APV inhibited this pre-treatment effect. It appears that the pre-treatment
      of neuronal cells with glutamate or NMDA in the absence of extracellular Ca2+
      promotes the Ca2+ influx-dependent process executing cell death. The pre
      treatment itself did not change the pattern of intracellular Ca2+ elevation by
      the activation of NMDA receptors. These results imply that glutamate activation
      of NMDA receptors consists of two different categories of pathways relating to
      neuronal cell death, i.e., Ca2+ influx independent and dependent, and that the
      former facilitates the latter to drive neuronal cells to death. This study
      clarified a mechanism by which glutamate quickly determines cell fate.

PMID- 15722058
TI  - Dopamine transporter function differences between male and female CD-1 mice.
AB  - It has been reported that male mice are more susceptible to the neurotoxic
      effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA)
      system. Since MA utilizes the dopamine transporter (DAT) to exert its effects, in
      the present study, we tested for differences in the dynamics of DAT function
      between male and female mice as an approach to understand some of the bases for
      this sex difference in MA-induced NSDA neurotoxicity. To accomplish this goal, in
      Experiment 1, the amount of dopamine (DA) obtained following DA infusion into the
      superfused striatal tissue fragments of male and female mice was measured while
      in Experiment 2 responses to the DA uptake blocker, nomifensine (NMF), were
      assessed in these preparations. The differences obtained to these treatments
      demonstrate that marked differences in DA transporter activity exist between male
      and female mice. When combining the DA and DOPAC measures from these two
      experiments, the data suggest that the female mice show a more active and
      efficient recovery and vesicular packaging of extracellular DA. These findings
      have important implications for sex differences in NSDA functions and responses
      to neurotoxins which enter the neurons via the DAT.

PMID- 15722059
TI  - Differential neuroprotective effects for three GABA-potentiating compounds in a
      model of hypoxia-ischemia.
AB  - Clomethiazole (CMZ) is a GABA(A)-potentiating compound; however, it is unclear
      whether this mode of action is responsible for its neuroprotective effects in
      animal models of ischemia. This study compared the neuroprotective efficacies of
      muscimol and midazolam, two potent GABA(A)-potentiating compounds, to that of CMZ
      in a model of hypoxia-ischemia (H-I). To establish a neuroprotective profile for
      CMZ, CMZ (60, 95, or 125 mg kg-1, i.p.) was administered to post-natal day 25
      male rats at numerous post-hypoxic time points and the rats were sacrificed 1 or
      4 weeks later. Varying degrees of histological protection were evident when CMZ
      was administered 1, 2, or 3 h post-hypoxia with the 125 mg kg-1 dose producing
      complete histological protection if administered 3 h post-hypoxia. To determine
      whether midazolam or muscimol could match the protection provided by CMZ
      administered 3 h post-hypoxia, H-I rats received varying doses of these compounds
      3 h post-hypoxia and were sacrificed 1 week later. Under identical conditions, no
      dose of muscimol or midazolam provided equivalent neuroprotection to that
      provided by CMZ. In fact, muscimol showed no neuroprotective ability whatsoever.
      Thus, CMZ, administered as late as 3 h post-hypoxia, was able to completely
      prevent H-I-induced cell death while a full dose range of other GABA-potentiating
      agents did not. Such direct comparison of these compounds in this model suggests
      the mechanism underlying the protective effects of CMZ may not rely solely on
      GABA(A)-potentiating properties. Elucidation of a novel mechanism of action for
      CMZ may expose new therapeutic targets in stroke treatment.

PMID- 15722060
TI  - Phenidone, a dual inhibitor of cyclooxygenases and lipoxygenases, ameliorates rat
      paralysis in experimental autoimmune encephalomyelitis by suppressing its target
      enzymes.
AB  - This study examined whether phenidone, a dual inhibitor of cyclooxygenase (COX)
      and lipoxygenase (LOX), affects the clinical symptoms of experimental autoimmune
      encephalomyelitis (EAE) in the rat, and the expression of both COX-1/-2 and 5-LOX
      in EAE spinal cords. Oral phenidone (200 mg/kg) significantly suppressed the
      incidence and clinical severity of EAE paralysis. Western blot analysis showed
      that phenidone significantly inhibited the increases in COX-1/-2 and 5-LOX in the
      spinal cords of rats with EAE. This finding was paralleled by immunohistochemical
      observations. Overall, these findings suggest that COX-1/-2 and 5-LOX are
      important inflammatory mediators in the pathogenesis of EAE, and that the
      inhibition of both COX and LOX ameliorates the autoimmune disorder of the central
      nervous system.

PMID- 15722061
TI  - Direct projections from CA1 to the superior temporal sulcus in the monkey,
      revealed by single axon analysis.
AB  - Anterograde tracer injections in the middle sector of CA1 in macaque monkeys
      demonstrate a direct projection to the fundus of the anterior superior temporal
      sulcus, in area IPa. Terminations are predominantly in layer 3. With regard to
      both terminal and arbor configuration, these hippocampal-cortical connections are
      morphologically similar to corticocortical connections to temporal association
      cortex. This report provides additional evidence of direct CA1 connections to
      particular multimodal cortical areas.

PMID- 15722062
TI  - Different expression of brain-derived neurotrophic factor in the nucleus
      accumbens of alcohol-preferring (P) and -nonpreferring (NP) rats.
AB  - Recent studies suggest that the gene that encodes brain-derived neurotrophic
      factor (BDNF) might be linked with vulnerability to alcohol abuse. We have now
      compared BDNF protein levels in several brain regions between alcohol-naive
      alcohol-preferring (P) and -nonpreferring (NP) rats using the enzyme-linked
      immunosorbent assay (ELISA) procedure. The results showed that BDNF levels in the
      nucleus accumbens of the P rats were significantly lower than those of the NP
      rats, suggesting that this innate difference may contribute to the disparate
      alcohol drinking behavior of the P and NP rats.

PMID- 15722063
TI  - Risks of mifepristone abortion in context.

PMID- 15722064
TI  - Twenty micrograms vs. >20 microg estrogen oral contraceptives for contraception:
      systematic review of randomized controlled trials.
AB  - Concern about estrogen-related adverse effects has led to progressive reductions
      in the estrogen dose in combination oral contraceptives (COCs). This review of
      randomized controlled trials tested the hypothesis that COCs containing <or=20
      microg ethinyl estradiol (EE) perform similarly to those containing >20 microg in
      terms of contraceptive effectiveness, bleeding patterns, discontinuation and side
      effects. Data from the 18 eligible trials conducted to date are inadequate for
      detecting possible differences in contraceptive effectiveness. Several COCs
      containing 20 microg EE resulted in higher rates of early trial discontinuation
      (overall and due to adverse events such as irregular bleeding) as well as
      increased risk of bleeding disturbances (both amenorrhea/infrequent bleeding and
      irregular, prolonged, frequent bleeding or breakthrough bleeding or spotting)
      than their higher-estrogen comparison pills. However, most trials compared COCs
      containing different progestin types, and changes in bleeding patterns could be
      related to progestin type as well as estrogen dose. While health care providers
      and women might select COCs containing 20 microg EE based on theoretical
      improvements in safety profile from the reduced dose of estrogen, no evidence is
      available to support this choice.

PMID- 15722065
TI  - Bone mineral density in women aged 40-49 years using depot-medroxyprogesterone
      acetate, norethisterone enanthate or combined oral contraceptives for
      contraception.
AB  - Most studies show that depot-medroxyprogesterone acetate (DMPA) has a negative
      effect on bone mass. There are conflicting reports with respect to recovery of
      bone mass with long-term use of DMPA. No information is available on the effect
      of norethisterone enanthate (NET-EN) on bone mass, and combined oral
      contraceptives (COCs) have not been found to be associated with loss of bone
      mass. The aim of this study was to investigate bone mineral density (BMD) in
      older women (40-49 years) in relation to use of DMPA, NET-EN and COCs for at
      least 12 months preceding recruitment into the study. One-hundred twenty-seven
      users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser
      controls. Bone mineral density was measured at the distal radius and midshaft of
      the ulna using dual X-ray absorptiometry. There was no significant difference in
      BMD between the four contraceptive user groups (p=.26) with and without
      adjustment for age. Although a small decrease in BMD was noted in the age range
      of 40-49 years, this was not statistically significant (p=.7). The BMD was found
      to be significantly associated with body mass index (BMI) (p<or=.0001) at both
      measurement sites, with an increase of one unit of BMI translating to an increase
      of 0.0044 g/cm2 in radius BMD. Follicle-stimulating hormone (FSH) level >or=25.8
      mIU/mL was associated with a decrease of 0.017 g/cm2 in radius BMD relative to
      women with FSH <25.8 mIU/mL. Significant interaction between FSH and BMI in their
      effect on BMD was observed (p=.006). This study found no evidence that long-term
      use of DMPA, NET-EN and COCs affects BMD in this population.

PMID- 15722066
TI  - Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a
      combined oral contraceptive: a 1-year randomized trial.
AB  - This open-label, randomized, Phase III study compared the efficacy and
      tolerability of and compliance with NuvaRing, a combined contraceptive vaginal
      ring releasing 15 microg of ethinylestradiol (EE) and 120 microg of etonogestrel
      daily, with those of and with a combined oral contraceptive (COC) containing 150
      microg of levonorgestrel (LNG) and 30 microg of EE. Subjects received NuvaRing or
      a COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring
      /pill-free period). A total of 1030 subjects (NuvaRing, n=512; COC, n=518) was
      randomized and started treatment (intent-to-treat [ITT] population). The
      percentage of women in the ITT population who completed the trial was 70.9% for
      the NuvaRing group and 71.2% for the COC group. Five in-treatment pregnancies
      occurred in each group, giving Pearl indices of 1.23 for NuvaRing and 1.19 for
      the COC. Compliance with both treatments was excellent and both were well
      tolerated. In conclusion, NuvaRing has comparable efficacy and tolerability with
      a COC containing 150 microg of LNG and 30 microg of EE and does not require daily
      dosing.

PMID- 15722068
TI  - Interpretation of the BBT chart: using the "Gap" technique compared to the
      Coverline technique.
AB  - OBJECTIVE: The aim of the study was to compare the accuracy of the Gap and
      Coverline techniques of interpreting the basal body temperature chart. METHODS:
      We compared the proportion of menstrual cycles for which the Gap and Coverline
      techniques accurately identified the post-ovulatory final fertile phase (FFP) and
      the initial infertile phase (IIP) and the median number of days each
      overestimated the fertile period, using urinary LH testing as the gold standard.
      RESULTS: The Gap and Coverline techniques identified the FFP within +/-1 day of
      that identified by LH testing in 13/33 (39%) and 10/33 (30%) cycles (chi2=0.6;
      p=.44), respectively, and the IIP within +1 day of that of LH testing in 13/33
      (55%) and 4/33 (12%) cycles, respectively (chi2=13.4; p<.001). The Gap and
      Coverline techniques overestimated the fertile period by 1 and 4 days,
      respectively (p=.0002). CONCLUSION: Based on this small study, the Gap technique
      appears to be more accurate than the Coverline technique in identifying the post
      ovulatory IIP.

PMID- 15722067
TI  - Comparison of the metabolic effects of oral contraceptive and nonhormonal
      contraceptive use in women over 40 years old.
AB  - The aim of this study was to compare metabolic changes during use of low-dose
      combined oral contraceptives (COCs) and those of nonhormonal contraceptives in
      perimenopausal women. Thirty-nine healthy women over 40 years old who attended
      the Family Planning Clinic of the King Chulalongkorn Memorial Hospital, Bangkok,
      Thailand, were recruited, 20 in the COC group received COC preparations
      containing 30 microg of ethinyl estradiol and 150 microg of levonorgestrel and 19
      in the nonhormonal group were intrauterine device users. Blood samples were taken
      upon admission and 6 months later. Minor biochemical changes associated with low
      dose COC use included an increase in glucose tolerance, triglycerides, serum
      albumin, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic
      pyruvic transaminase (SGPT) levels but a decrease in fasting plasma glucose,
      total cholesterol, high-density lipoprotein cholesterol, total bilirubin and
      alkaline phosphatase levels. There was no clinical significance for the metabolic
      changes. Low-dose COCs can be a satisfactory contraceptive choice for healthy
      perimenopausal women.

PMID- 15722069
TI  - A short-scheme protocol of gemeprost for midtrimester termination of pregnancy
      with uterine scar.
AB  - OBJECTIVE: The purpose of this study is to investigate the safety and
      effectiveness of a short-scheme protocol of gemeprost for second trimester
      induction of abortion in women with previous uterine surgery. STUDY DESIGN:
      Retrospective review of women who underwent second trimester medical termination
      of pregnancy (TOP) at our hospital in a 5-year period. A short regimen of
      gemeprost was used: over a 24-h period, 1 mg vaginal gemeprost was given every 3
      h up to three doses after which, if abortion did not occur, another course at the
      same dosage schedule was administered up to 4 days. Induction failure was defined
      as women undelivered by 96 h. A homogeneous population was identified.
      Statistical analysis was performed with the chi(2) test or Fisher's Exact Test
      for categorical data and t test for continuous variables. RESULTS: Four hundred
      seventeen women underwent medical midtrimester TOP in the 5-year study period.
      Two hundred five patients were selected for this review, comparing 63 patients
      with scarred uterus to 142 women without uterine scars. There were no differences
      between the two groups in induction-to-abortion interval and number of pessaries
      given. The overall failure of induction rate was 1.5% and need for blood
      transfusion was 0.5%. No uterine rupture was reported. CONCLUSION: The regimen of
      gemeprost proposed seems to be as safe and effective in patients with uterine
      scars as in women with unscarred uteri with a very low incidence of
      complications.

PMID- 15722070
TI  - Bioavailability of the Yuzpe and levonorgestrel regimens of emergency
      contraception: vaginal vs. oral administration.
AB  - Separate crossover studies compared the bioavailability of oral vs. vaginal
      routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of
      emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg
      of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel
      regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week
      later, each subject received orally the standard dose of the assigned medication.
      Serial blood samples were collected over 24 h and assayed for levonorgestrel and
      ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to
      compare oral vs. vaginal administration for maximum concentration (Cmax), time to
      maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24).
      Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal
      administration of double the standard dose of the Yuzpe regimen resulted in a
      lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs.
      2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding
      ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and
      peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative
      bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%,
      respectively. Similarly, vaginal administration of the levonorgestrel regimen
      resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later
      Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration.
      The relative bioavailability was 62%. Our preliminary data suggest that vaginal
      administration of these emergency contraception regimens appears to require at
      least three times the standard oral dose to achieve equivalent systemic
      levonorgestrel concentrations.

PMID- 15722071
TI  - The remaining barriers to the use of emergency contraception: perception of
      pregnancy risk by women undergoing induced abortions.
AB  - Although access to and knowledge of emergency contraception (EC) have improved,
      numerous unplanned pregnancies occur each year. We thus assessed the remaining
      barriers to EC use in a population of women seeking an abortion in four abortion
      centers in France in 2002. A self-administered questionnaire was completed by
      1365 women. Most women have heard of EC (89%), but access to information remained
      limited in socially disadvantaged populations. Nevertheless, the unperceived risk
      of pregnancy appeared to be the most limiting factor to EC use. Only 38.5% of
      women were aware of pregnancy risk at the time of the intercourse that made them
      pregnant. Of these women, 48% minimized the risk later, resulting in the decision
      not to use EC. As the perception of risk is commonly reevaluated by women over
      time, which probably affects EC use, it could be important to promote advance
      supply of EC so that women could use it immediately after a recognized
      unprotected intercourse.

PMID- 15722072
TI  - Valuable safeguard or unnecessary burden? Characterization of physician
      consultations for oral contraceptive use in Mexico City.
AB  - CONTEXT: Given the safety and efficacy of oral contraceptives (OCs), many health
      professionals believe that these should be widely available over-the-counter
      (OTC). Opponents of OTC availability argue that without a physician's
      consultation, women will not be properly screened and will not use OCs correctly,
      thereby compromising safety and efficacy. However, little is known about the
      content or quality of physicians' consultations. METHODS: Trained simulated
      patients (SPs) attended 45 appointments with Mexico City public and private
      physicians to request a prescription for OCs. Immediately following each
      appointment, the SPs filled out a checklist regarding the information provided
      and examinations performed by physicians. RESULTS: Both public and private
      physicians asked a few questions and provided little information regarding
      screening, pill-taking instructions, side effect information and warning sign
      information. Despite the fact that all SPs were appropriate OC candidates, women
      were denied a prescription in seven (15.6%) appointments mostly because of their
      age (regarded as either too old or too young). CONCLUSION: In general, Mexican
      physicians are not providing women thorough information and screening in OC
      consultations, calling into question the assumption that a physician's
      appointment is necessary for or will ensure safe, proper OC use.

PMID- 15722073
TI  - Preclinical evaluation for noninvasive reversal following long-term vas occlusion
      with styrene maleic anhydride in langur monkeys.
AB  - A preclinical evaluation for reversal through a noninvasive approach following
      long-term vas occlusion with styrene maleic anhydride (SMA) has been attempted in
      langur monkeys at the level of semen parameters, sperm functional tests, semen
      biochemistry, histology and ultrastructure of reproductive organs, hematology and
      serum clinical biochemistry including antisperm antibodies (ASA), prostate
      specific antigen (PSA) and testosterone. Noninvasive reversal through palpation,
      percutaneous squeezing and electrical stimulation, forced vibratory movements and
      suprapubic percussion in the inguinal segments and per-rectal digital massage was
      attempted in seven langur monkeys after 540 days following vas occlusion. The
      results revealed instant azoospermia reversal on the same day of reversal with
      impaired sperm quality, which showed gradual improvement and normospermia with
      normal motility and viability after 60-90 days of reversal. Sperm functional
      tests, including ultrastructure of spermatozoa, indicative of sterility in the
      initial ejaculations, reached normalcy after 90-120 days of reversal. The seminal
      plasma biochemistry indicative of obstructive azoospermia regained a normal
      pattern after 90-120 days of reversal. The morphology of testes that showed focal
      degeneration during 540 days of vas occlusion and that of vasa deferentia that
      showed exfoliation of epithelial cells resumed to normal morphology comparable
      with control animals after 150 days of reversal. The morphology of the
      epididymis, seminal vesicle and prostate did not show appreciable changes
      following vas occlusion and after noninvasive reversal compared with those of
      control animals. Hematology, serum clinical chemistry, ASA, PSA and testosterone
      fluctuated within control limits, indicating safety of the procedure at the level
      of accessory reproductive organs. The results suggest that noninvasive reversal
      is feasible even after long-term vas occlusion with SMA and is safe without
      adverse side effects.

PMID- 15722074
TI  - Blastocyst implantation failure in mice due to "nonreceptive endometrium":
      endometrial alterations by Hibiscus rosa-sinensis leaf extract.
AB  - Many plants are known to possess antifertility activity. However, limited
      attempts have been made to scientifically evaluate these claims. Hibiscus rosa
      sinensis flowers have been shown to possess antifertility and abortifacient
      activity. In this report, antiimplantation activity of water extract of leaves of
      H. rosa-sinensis was investigated. Pregnant female mice were dosed with extract
      (100 mg/kg body weight) from days 1 to 6 of pregnancy. No implantation sites were
      observed in treated animals when they were surgically opened on day 15 of
      pregnancy. Biochemical and biophysical alterations were observed in the
      endometrium in treated animals, especially on day 5, at 4:40 a.m., the day of
      implantation. A sharp increase in superoxide anion radical and a sharp fall in
      superoxide dismutase (SOD) activity, as seen in the endometrium from control
      animals, were altered in treated animals. The extract also exhibited
      antiestrogenic activity, as judged by increase in uterine weight. The
      physiological alterations induced by water extract of H. rosa-sinensis are
      discussed.

PMID- 15722075
TI  - Failed medical termination of twin pregnancy with mifepristone: a case report.
AB  - Medical abortion with mifepristone and misoprostol is a two-step process where
      some women will change their minds about going through the abortion process after
      taking mifepristone. Of these, some pregnancies will continue. A woman with a
      twin pregnancy who changed her mind is presented. Twin pregnancies may need
      higher dosages of mifepristone than single pregnancies due to the presence of two
      corpora lutea and increased amount of trophoblast tissue. There is little, if
      any, documentation regarding congenital abnormalities after taking mifepristone.
      Therefore, there is little evidence to support persuasion of the patient to
      continue the abortion process with the prostaglandin analouge.

PMID- 15722076
TI  - Leishmania braziliensis: a novel mechanism in the lipophosphoglycan regulation
      during metacyclogenesis.
AB  - During metacyclogenesis of Leishmania in its sand fly vector, the parasite
      differentiates from a noninfective, procyclic form to an infective, metacyclic
      form, a process characterised by morphological changes of the parasite and also
      biochemical transformations in its major surface lipophosphoglycan (LPG). This
      lipid-anchored polysaccharide is polymorphic among species with variations in
      sugars that branch off the conserved Gal(beta1,4)Man(alpha1)-PO4 backbone of
      repeat units and the oligosaccharide cap. Lipophosphoglycan has been implicated
      as an adhesion molecule that mediates the interaction with the midgut epithelium
      of the sand fly in the subgenus Leishmania. This paper describes the LPG
      structure for the first time in a species from the subgenus Viannia, Leishmania
      (Viannia) braziliensis. The LPG from the procyclic form of L. braziliensis was
      found to lack side chain sugar substitutions. In contrast to other species from
      the subgenus Leishmania, metacyclic forms of L. braziliensis makes less LPG and
      add 1-2 (beta1-3) glucose residues that branch off the disaccharide-phosphate
      repeat units of LPG. Thus, this represents a novel mechanism in the regulation of
      LPG structure during metacyclogenesis.

PMID- 15722077
TI  - Population genetics of complex life-cycle parasites: an illustration with
      trematodes.
AB  - Accurate inferences on population genetics data require a sound underlying
      theoretical null model. Organisms alternating sexual and asexual reproduction
      during their life-cycle have been largely neglected in theoretical population
      genetic models, thus limiting the biological interpretation of population
      genetics parameters measured in natural populations. In this article, we derive
      the expectations of those parameters for the life-cycle of monoecious trematodes,
      a group comprising several important human and livestock parasites that
      obligatorily alternate sexual and asexual reproduction during their life-cycle.
      We model how migration rates between hosts, sexual and asexual mutation rates,
      adult selfing rate and the variance in reproductive success of parasites during
      the clonal phase affect the amount of neutral genetic diversity of the parasite
      (effective population size) and its apportionment within and between definitive
      hosts (using F-statistics). We demonstrate, in particular, that variance in
      reproductive success of clones, a parameter that has been completely overlooked
      in previous population genetics models, is very important in shaping the
      distribution of the genetic variability both within and among definitive hosts.
      Within definitive hosts, the parameter F(IS) (a measure of the deviation from
      random mating) is decreased by high variance in clonal reproductive success of
      larvae but increased by high adult self-fertilisation rates. Both clonal
      multiplication and selfing have similar effects on between-host genetic
      differentiation (F(ST)). Migration occurring before and after asexual
      reproduction can have different effects on the patterns of F(IS), depending on
      values of the other parameters such as the mutation rate. While the model applies
      to any hermaphroditic organism alternating sexual and clonal reproduction (e.g.
      many plants), the results are specifically discussed in the light of the limited
      population genetic data on monoecious trematodes available to date and their
      previous interpretation. We hope that our model will encourage more empirical
      population genetics studies on monoecious trematodes and other organisms with
      similar life-cycles.

PMID- 15722078
TI  - Local adaptation and enhanced virulence of Nosema granulosis artificially
      introduced into novel populations of its crustacean host, Gammarus duebeni.
AB  - Local adaptation theory predicts that, on average, most parasite species should
      be locally adapted to their hosts (more suited to hosts from local than distant
      populations). Local adaptation has been studied for many horizontally transmitted
      parasites, however, vertically transmitted parasites have received little
      attention. Here we present the first study of local adaptation in an
      animal/parasite system where the parasite is vertically transmitted. We
      investigate local adaptation and patterns of virulence in a crustacean host
      infected with the vertically transmitted microsporidian Nosema granulosis. Nosema
      granulosis is vertically transmitted to successive generations of its crustacean
      host, Gammarus duebeni and infects up to 46% of adult females in natural
      populations. We investigate local adaptation using artificial horizontal
      infection of different host populations in the UK. Parasites were artificially
      inoculated from a donor population into recipient hosts from the sympatric
      population and into hosts from three allopatric populations in the UK. The
      parasite was successfully established in hosts from all populations regardless of
      location, infecting 45% of the recipients. Nosema granulosis was vertically
      (transovarially) transmitted to 39% of the offspring of artificially infected
      females. Parasite burden (intensity of infection) in developing embryos differed
      significantly between host populations and was an order of magnitude higher in
      the sympatric population, suggesting some degree of host population specificity
      with the parasite adapted to its local host population. In contrast with natural
      infections, artificial infection with the parasite resulted in substantial
      virulence, with reduced host fecundity (24%) and survival (44%) of infected hosts
      from all the populations regardless of location. We discuss our findings in
      relation to theories of local adaptation and parasite-host coevolution.

PMID- 15722079
TI  - Evaluation of a Real-time PCR-based assay using the lightcycler system for
      detection of Toxoplasma gondii bradyzoite genes in blood specimens from patients
      with toxoplasmic retinochoroiditis.
AB  - PCR based methods have advantages over traditional methods for the diagnosis of
      toxoplasmosis, especially when serology fails and clinical symptoms are not
      evident. However, current PCR-based assays are often labour-intensive and not
      readily quantifiable and have the potential for contamination due to a
      requirement for postamplification sample handling. Real-time PCR can address
      these limitations. We have developed and evaluated a highly sensitive Real-time
      PCR (Light-cycler, LC-PCR) to detect and quantify Toxoplasma gondii B1 and
      bradyzoite specific genes (SAG-4, MAG-1) in serum and peripheral blood
      mononuclear cells (PBMC) specimens, from five immunocompetent subjects with
      clinically suspected toxoplasmic retinochoroiditis (TRC) or without a suspected
      T. gondii infection. A standard curve for quantitation of parasitic load was
      generated using SYBR Green I fluorescent detection. The results were compared
      with those obtained with a nested PCR (n-PCR). In TRC patients, both PCR methods
      confirmed ophtalmoscopy and fluorangiographic findings. Among the TRC patients,
      the use of LC-PCR was more sensitive than n-PCR for detection and quantification
      of either B1 gene (P<0.001) or SAG-4/MAG-1 gene (P<0.05). LC-PCR has been shown
      particularly useful to accurately determine the parasite DNA load in follow-up
      specimens in whom the performance of either B1 or SAG-4 and MAG-1 in detecting T.
      gondii loads, varied with respect to specific antitoxoplasmic treatment.

PMID- 15722080
TI  - Identification and disruption of a rhoptry-localized homologue of sodium hydrogen
      exchangers in Toxoplasma gondii.
AB  - Na+/H+ exchangers (NHEs) are ubiquitous membrane proteins that catalyze the
      exchange of Na+ for H+ and are critical in pH and cell volume regulation, as well
      as osmotolerance. In this study, we identify and characterize a novel NHE,
      TgNHE2, in Toxoplasma gondii. Immunofluorescence studies show that TgNHE2 is
      localized to the rhoptries, secretory organelles involved in invasion. TgNHE2 is
      the first intracellular NHE to be characterized in a protozoan parasite and its
      localization suggests possible roles for the rhoptries in osmotolerance and/or as
      secretory lysosomes-like granules.

PMID- 15722081
TI  - Carbohydrates that mimic schistosome surface coat components affect ERK and PKC
      signalling in Lymnaea stagnalis haemocytes.
AB  - Molluscs are intermediate hosts for helminth parasites such as Schistosoma spp.
      that possess an immunogenic surface coat of high carbohydrate content, with
      fucose as the predominant saccharide. More than a decade ago, it was postulated
      that such components could block receptors on snail haemocytes thus preventing
      recognition of intra-molluscan schistosome stages. Although more recent studies
      have shown that carbohydrates can suppress processes such as phagocytosis by
      haemocytes, interference of the haemocyte cell signalling pathways that regulate
      immunity by saccharides has not yet been investigated. We have recently reported
      the presence of extracellular-signal regulated kinase and protein kinase C in
      Lymnaea stagnalis haemocytes. Here we show that extracellular-signal regulated
      kinase and protein kinase C activities are down-regulated when haemocytes are
      exposed to albumin-linked fucose and galactose in the absence of haemolymph.
      Moreover, we demonstrate that phagocytosis is reduced under these conditions.
      Interestingly, in the presence of haemolymph, only protein kinase C activity is
      down-regulated and only galactose suppresses phagocytosis, implying a role for
      serum factors in the preservation of haemocyte function following exposure. We
      therefore propose that the establishment of a compatible relationship between a
      schistosome and its snail host is at least in part due to down-regulation of cell
      signalling events in haemocytes.

PMID- 15722082
TI  - Cloning and characterisation of an aspartyl protease inhibitor (API-1) from
      Ancylostoma hookworms.
AB  - Hookworm infection persists as a public health problem in developing nations.
      Vaccine-based strategies offer the best chance of long-term control. Aspartyl
      protease inhibitors from parasitic nematodes are highly immunogenic, and have
      been suggested as potential vaccine antigens. An aspartyl protease inhibitor, API
      1, was cloned and characterised from the hookworms Ancylostoma caninum and
      Ancylostoma ceylanicum. Using sequence from the hookworm expressed sequence tag
      project, specific primers were designed and used to amplify Ac-api-1 from A.
      caninum infective L3 cDNA by PCR. Amplicons from the 5' and 3' ends were cloned,
      sequenced, and combined to create an 874-bp full-length composite sequence of the
      Ac-api-1 gene. The A. ceylanicum api-1 cDNA of 878 bp was cloned from L3 cDNA
      using the A. caninum primers. The amino acid sequences of hookworm orthologues
      were nearly identical, and database searching indicated they belonged to the
      aspin family, a group of nematode specific aspartyl protease inhibitors that
      includes the Ascaris pepsin inhibitor PI-3. Ac-api-1 mRNA was detected by reverse
      transcriptase PCR in eggs, L1, L3 and adult life cycle stages. A polyclonal
      antiserum against Escherichia coli expressed recombinant Ac-API-1 detected the
      protein in adult A. caninum excretory/secretory products, but not in those from
      activated infective larvae. Immunolocalisation experiments using the antiserum
      indicated that Ac-API-1 is present primarily in the pseudocoelomic fluid in adult
      hookworms. Soluble, yeast-expressed Ac-API-1 failed to inhibit pepsin or a
      hookworm gut aspartyl protease in vitro, but inhibited approximately 30% of the
      proteolytic activity of adult excretory/secretory products. The pseudocoleomic
      location, presence in all life cycle stages, lack of inhibitory activity against
      pepsin, and inhibitory activity against excretory/secretory products suggest that
      Ac-API-1 inhibits an unidentified, putative aspartyl protease secreted by adult
      hookworms, and may be released as an enzyme-inhibitor complex. The highly
      immunogenic properties of nematode aspins suggest that Ac-API-1 represents a
      promising target for a recombinant hookworm vaccine.

PMID- 15722083
TI  - Effects of temperature on fecundity in vitro, egg hatching and reproductive
      development of Benedenia seriolae and Zeuxapta seriolae (Monogenea) parasitic on
      yellowtail kingfish Seriola lalandi.
AB  - Globally, aquaculture industries involved with commercial culture of kingfish
      (Seriola spp.) experience outbreaks of monogenean parasites, which can cause
      heavy stock losses. In Australia and New Zealand, aquaculturists of kingfish
      Seriola lalandi incur financial losses caused by two monogenean species:
      Benedenia seriolae and Zeuxapta seriolae which parasitise the skin and gills,
      respectively. This study provides information on some basic temperature-dependent
      life-cycle parameters of these problematic monogeneans on S. lalandi. Hatching
      times and age at maturity were inversely related to water temperature within the
      range experienced by wild kingfish in New Zealand (13-21 degrees C). Mature B.
      seriolae in vitro laid on average 37 eggs/day that hatched over approximately 4
      days; peak hatching occurred 9, 11 and 22 days post-deposition at temperatures of
      21, 17.5 and 13+/-1.0 degrees C, respectively. Z. seriolae in vitro laid on
      average 246 eggs/day that hatched over 2 days; peak hatching occurred 7, 9 and 15
      days post-deposition at these respective temperatures. B. seriolae matured within
      20, 25 and 48 days p.i. at 21, 18 and 13 degrees C. Z. seriolae matured within
      25, 37 and >52 days p.i. at the same temperatures. This research describes stages
      in the reproductive development of B. seriolae and Z. seriolae and discusses the
      inclusion of basic parasitic life-cycle parameters into management strategies
      designed to maximise treatment efficacy and limit monogenean epizootics in sea
      cage kingfish culture.

PMID- 15722084
TI  - The consequences of short-term grazing of bioactive forages on established adult
      and incoming larvae populations of Teladorsagia circumcincta in lambs.
AB  - The objective of this study was to investigate the consequences of short-term
      grazing on bioactive forages on (i) the viability and fecundity of established
      adult Teladorsagia circumcincta population and (ii) the establishment and
      development of incoming T. circumcincta infective larvae. Forty-eight, parasite
      naive, 3-month old, grazing lambs were artificially infected with 8000 infective
      larvae of T. circumcincta on day 1 of the experiment. On day 21 p.i., lambs were
      allocated to one of three bioactive forage grazing treatments; chicory (Cichorium
      intybus), sulla (Hedysarum coronarium), lotus (Lotus pedunculatus), and the
      control grass/clover (Lolium perenne/Trifolium repens) forage. On day 28 of the
      experiment a second dose of 8000 T. circumcincta infective larvae was
      administered to the lambs to investigate the effects of forages on the ability of
      infective larvae to establish within the host. All animals were slaughtered for
      worm recovery on day 35, while liveweight gain, feacal egg counts (FEC) and total
      worm egg output were monitored regularly throughout the experiment. Although FEC
      or total egg output were similar among the groups, adult worm burdens at
      slaughter were significantly affected (P<0.05) by forage treatment during the 2
      week grazing period. Lambs grazing chicory had the lowest adult worm burdens and
      significantly lower numbers of male worms compared to those grazing on
      grass/clover (P<0.01), while the lambs grazing on sulla or lotus had similar
      adult populations to grass/clover fed animals. The results from the worm
      recoveries of the second dose (immature worm burdens) were affected by
      physiologically and/or immunologically mediated mechanisms, which reduced larval
      establishment in all treatments. Nevertheless, immature worm burdens at slaughter
      were similar between chicory, sulla and grass/clover group, while the immature
      worm recoveries from the lotus group were significantly higher (P<0.05) compared
      to those from lambs grazing grass/clover. Overall, the results of the present
      study support the view that chicory can be a promising candidate species in
      pasture management practices to control T. circumcincta burdens.

PMID- 15722085
TI  - Bos taurus and Bos indicus (Sahiwal) calves respond differently to infection with
      Theileria annulata and produce markedly different levels of acute phase proteins.
AB  - Disease-resistant livestock could provide a potentially sustainable and
      environmentally sound method of controlling tick and tick-borne diseases of
      livestock in the developing world. Advances in the knowledge and science of
      genomics open up opportunities to identify selectable genes controlling disease
      resistance but first, breeds and individuals with distinguishable phenotypes need
      to be identified. The Bos indicus breed, Sahiwal, has been exploited in dairy
      breeding programmes, because it is resistant to ticks and has relatively good
      performance characteristics compared to other indigenous cattle breeds of
      tropical regions. The analyses reported here show that Sahiwal calves were also
      more resistant than European Bos taurus (Holstein) dairy breed calves to tick
      borne tropical theileriosis (Theileria annulata infection). Following
      experimental infection with T. annulata sporozoites, a group of Sahiwal calves
      all survived without treatment, with significantly lower maximum temperatures
      (P<0.01) and lower rates of parasite multiplication (P<0.05) than a group of
      Holstein calves, which all had severe responses. Although the Sahiwals became as
      anaemic as the Holsteins, other measures of pathology, including enlargement of
      the draining lymph node and the acute phase proteins, alpha1 acid glycoprotein
      and haptoglobin, were significantly less in the Sahiwals than in the Holsteins
      (P<0.05). Additionally, the Sahiwals had significantly lower resting levels of
      alpha1 acid glycoprotein than the Holsteins (P<0.05). Production of a third acute
      phase proteins, serum amyloid A, had very similar kinetics in both breeds. Acute
      phase proteins are produced in response to systemic release of the kinds of pro
      inflammatory cytokines that are thought to be responsible for the pyrexic,
      cachectic and anorexic responses characteristic of tropical theileriosis. The
      prolonged production of alpha1 acid glycoprotein in the Holsteins is indicative
      of chronic production of circulating pro-inflammatory cytokines. In contrast,
      Sahiwals appear able to overcome infection with T. annulata as well as limit
      pathology by preventing the over-stimulation of pathways involving these
      cytokines.

PMID- 15722086
TI  - Transcript and protein environmental biomarkers in fish--a review.
AB  - The levels of contaminant-affected gene products (transcripts and proteins) are
      increasingly utilized as environmental biomarkers, and their appropriate
      implementation as diagnostic tools is discussed. The required characteristics of
      a gene product biomarker are accurate evaluation using properly normalized
      absolute units, aiming at long-term comparability of biomarker levels over a wide
      geographical range and among many laboratories. Quantitative RT-PCR and
      competitive ELISA are suggested as preferred evaluation methods for transcript
      and protein, respectively. Constitutively expressed RNAs or proteins which are
      part of the examined homogenate are suggested as normalizing agents, compensating
      for variable processing efficiency. Essential characterization of expression
      patterns is suggested, providing reference values to be compared to the monitored
      levels. This comparison would enable estimation of the intensity of biological
      effects of contaminants. Contaminant-independent reference expression patterns
      should include natural fluctuations of the biomarker level. Contaminant-dependent
      patterns should include dose response to model contaminants chronically
      administered in two environmentally-realistic routes, reaching extreme sub-lethal
      affected levels. Recent studies using fish as environmental sentinel species,
      applying gene products as environmental biomarkers, and implementing at least
      part of the depicted methodologies are reviewed.

PMID- 15722087
TI  - Investigation of acute toxicity of chlorpyrifos-methyl on Nile tilapia
      (Oreochromis niloticus L.) larvae.
AB  - Chlorpyrifos-methyl, a wide-spectrum organophosphorus insecticide and potential
      toxic pollutant contaminating aquatic ecosystems, was investigated for acute
      toxicity. Larvae of the freshwater fish Nile tilapia (Oreochromis niloticus L.)
      were selected for the bioassay experiments. The experiments were repeated three
      times and the 96 h LC50 was determined for the larvae. The static test method for
      assessing acute toxicity was used. Water temperature was maintained at 25+/-1
      degrees C. In addition, behavioral changes at each chlorpyrifos-methyl
      concentration were observed for the individual fish. Data obtained from the
      chlorpyrifos-methyl acute toxicity tests were evaluated using Finney's probit
      analysis statistical method. The 96 h LC50 value for Nile tilapia larvae was
      calculated to be 1.57 mg/l.

PMID- 15722088
TI  - Copper and Zn uptake by radish and pakchoi as affected by application of
      livestock and poultry manures.
AB  - Environmental safety of agricultural utilization of livestock and poultry manures
      from intensive farming is attracting great attention because the manures often
      contain high concentrations of heavy metals and organic pollutants. Pot
      experiments, in which a pig manure (PM), a chicken manure (CM) and a commercial
      organic manure (OM) with different concentrations of Cu and Zn to simulate soil
      metal accumulation by manure application for different times were utilized in a
      garden soil at a rate of 2% (W/W), were conducted to study the effect of
      application of these livestock and poultry manures on growth of radish (Raphanus
      sativus L.) and pakchoi (Brassica chinensis L.) as well as their Cu and Zn
      uptake. The results exhibit that the manures except the PM improved the growth of
      radish and pakchoi. The difference of biomass among the same manure treatments
      containing different concentrations of Cu and Zn, however, was insignificant. In
      addition, application of the livestock and poultry manures significantly
      increased soil pHs and electric conductivities (EC) compared with the control,
      which is ascribed that these manures had high pH and contained large amounts of
      inorganic ions. The available soil Zn concentrations in the PM were higher than
      that in the CM and OM, and the extractable soil Cu concentrations in the three
      manures were almost the same after radish growth in the garden soil but were
      different after pakchoi growth. Zinc and Cu concentrations in the radish and
      pakchoi tissues increased when the soil Zn and Cu concentrations increased by
      manures application, but were still within a safe value. An except is the
      treatment PM4 in which the Zn concentration of the above-ground part of radish
      was 28.7 mg kg-1, exceeding the Chinese Food Hygiene Standard of 20 mg kg-1 based
      on fresh weight. Good correlation was obtained between the extractable soil Zn
      (or Cu) concentrations extracted by 1.0 mol l-1 NH4NO3 and the Zn (or Cu)
      concentrations in radish and pakchoi tissues, which was expected to be effective
      in forecasting Cu and Zn availability to radish and pakchoi in manure agronomic
      utilization.

PMID- 15722089
TI  - Interpreting drinking water quality in the distribution system using Dempster
      Shafer theory of evidence.
AB  - Interpreting water quality data routinely generated for control and monitoring
      purposes in water distribution systems is a complicated task for utility
      managers. In fact, data for diverse water quality indicators (physico-chemical
      and microbiological) are generated at different times and at different locations
      in the distribution system. To simplify and improve the understanding and the
      interpretation of water quality, methodologies for aggregation and fusion of data
      must be developed. In this paper, the Dempster-Shafer theory also called theory
      of evidence is introduced as a potential methodology for interpreting water
      quality data. The conceptual basis of this methodology and the process for its
      implementation are presented by two applications. The first application deals
      with the interpretation of spatial water quality data fusion, while the second
      application deals with the development of water quality index based on key
      monitored indicators. Based on the obtained results, the authors discuss the
      potential contribution of theory of evidence as a decision-making tool for water
      quality management.

PMID- 15722090
TI  - Pollution resistance of mountain birch, Betula pubescens subsp. czerepanovii,
      near the copper-nickel smelter: natural selection or phenotypic acclimation?
AB  - Mountain birch, Betula pubescens subsp. czerepanovii (Orlova) Hamet-Ahti, is one
      of the very few woody plants surviving in the heavily polluted industrial barrens
      of the Kola Peninsula, north-western Russia. The present study was designed to
      find out whether long-lasting pollution impact caused selection of resistant
      birch genotypes, and to investigate possible trade-offs between pollution
      resistance and performance by exploring growth of birch seedlings in the
      different environments. In the reciprocal planting experiments, progenies of
      birches from polluted sites performed slightly better in the polluted environment
      (in terms of survival, leaf number, and leaf size) than progenies of birches from
      clean sites; and vice versa, in the clean environment progenies of birches from
      polluted sites performed slightly worse than progenies of birches from clean
      sites. However, this pattern was detected only in some of statistical tests,
      while the majority of comparisons showed no genotype or genotype by environment
      effects. Although some of the results indicate that long-lasting pollution impact
      may have increased pollution resistance of the affected populations by
      elimination of sensitive genotypes (survival selection), this conclusion should
      be considered tentative. The resistance did not reach the level sufficient to
      assure re-colonisation of polluted habitats: progenies of all trees completely
      died on the contaminated soils by the end of the first growth season. Therefore
      persistence of mountain birch populations near the strong polluters may be
      transient, being explained not only by higher resistance of the survivors, but
      also by phenotypic acclimatisation of mature trees to gradual increase in
      pollution.

PMID- 15722091
TI  - Initial risk assessment for three beta-blockers found in the aquatic environment.
AB  - Daphnia magna, Desmodesmus subspicatus and Lemna minor were used to determine the
      ecotoxicity of beta-blockers. Propranolol was the most toxic substance, with
      EC50s of 7.7 mg l-1 in the Daphnia test and 0.73 mg l-1 in the algal test. The
      toxicity of atenolol and metoprolol in the Daphnia test was very low, with EC50s
      of 313 and 438 mg l-1, respectively. In the algal test, metoprolol (EC50: 7.9 mg
      l-1) was more toxic than atenolol (EC50: 620 mg l-1). Lemna minor was the least
      sensitive species. All substances showed PEC/PNEC ratios <1, whereas propranolol
      with a ratio of 0.81 seems to be the most relevant substance and I recommend to
      perform chronic biotests to refine the estimate of the environmental risk. Taking
      bioconcentration factors (BCF) into account, resulting internal effect
      concentrations (IEC) differ only slightly, which means that the differences in
      the EC50 depend mainly on the diverse logP levels causing narcosis via disruption
      of membrane integrity. Predictions of toxicity using ECOSAR were close to the
      empirically measured data. Mixture toxicity of the three compounds could be
      predicted accurately using the concept of concentration addition.

PMID- 15722092
TI  - Effects of Ni, Cr, Hg, Cu, Zn, Al on the dissolved oxygen balance of streams.
AB  - Inorganic metals besides their direct toxic effects, carry the potential of
      causing serious variations on existing ecosystems in receiving waters. Self
      purification mechanism is vital for the continuity of the existing micro and
      macro living organisms in the streams. This mechanism is effected from the
      existence of metals. In this study, interferences of HgCl2, HgSO4, Ni(NO3)2,
      CrCl3, CuSO4.5H2O, K2Cr2O7, ZnSO4.7H2O and Al2(SO4)3.18H2O metal compounds on
      respirometric BOD and related effects on the self purification, are investigated
      with the representative formations of DO deficit curves. In the presence of these
      metals, streamwater BOD parameters and related DO deficit curve formations are
      significantly effected.

PMID- 15722093
TI  - Source contributions to fine particulate matter in an urban atmosphere.
AB  - This paper proposes a practical method for estimating source attribution by using
      a three-step methodology. The main objective of this study is to explore the use
      of the three-step methodology for quantifying the source impacts of 24-h PM2.5
      particles at an urban site in Seoul, Korea. 12-h PM2.5 samples were collected and
      analyzed for their elemental composition by ICP-AES/ICP-MS/AAS to generate the
      source composition profiles. In order to assess the daily average PM2.5 source
      impacts, 24-h PM2.5 and polycyclic aromatic hydrocarbons (PAH) ambient samples
      were simultaneously collected at the same site. The PM2.5 particle samples were
      then analyzed for trace elements. Ionic and carbonaceous species concentrations
      were measured by ICP-AES/ICP-MS/AAS, IC, and a selective thermal MnO2 oxidation
      method. The 12-h PM2.5 chemical data was used to estimate possible source
      signatures using the principal component analysis (PCA) and the absolute
      principal component scores method followed by the multiple linear regression
      analysis. The 24-h PM2.5 source categories were extracted with a combination of
      PM2.5 and some PAH chemical data using the PCA, and their quantitative source
      contributions were estimated by chemical mass balance (CMB) receptor model using
      the estimated source profiles and those in the literature. The results of PM2.5
      source apportionment using the 12-h derived source composition profiles show that
      the CMB performance indices; chi2, R2, and percent of mass accounted for are
      2.3%, 0.97%, and 100.7%, which are within the target range specified. According
      to the average PM2.5 source contribution estimate results, motor vehicle exhaust
      was the major contributor at the sampling site, contributing 26% on average of
      measured PM2.5 mass (41.8 microg m-3), followed by secondary sulfate (23%) and
      nitrate (16%), refuse incineration (15%), soil dust (13%), field burning (4%),
      oil combustion (2.7%), and marine aerosol (1.3%). It can be concluded that
      quantitative source attribution to PM2.5 in an urban area where source profiles
      have not been developed can be estimated using the proposed three-step
      methodology approach.

PMID- 15722094
TI  - Mercury body burdens in Gambusia holbrooki and Erimyzon sucetta in a wetland
      mesocosm amended with sulfate.
AB  - This study used an experimental model of a constructed wetland to evaluate the
      risk of mercury methylation when the soil is amended with sulfate. The model was
      planted with Schoenoplectus californicus and designed to reduce copper, mercury,
      and metal-related toxicity in a wastestream. The sediments of the model were
      varied during construction to provide a control and two levels of sulfate
      treatment, thus allowing characterization of sulfate's effect on mercury
      methylation and bioaccumulation in periphyton and two species of fish--eastern
      mosquitofish (Gambusia holbrooki) and lake chubsucker (Erimyzon sucetta). After
      one year in the experimental model, mean dry-weight normalized total mercury
      concentrations in mosquitofish from the non-sulfate treated controls (374+/-77
      ng/g) and the reference location (233+/-17 ng/g) were significantly lower than
      those from the low and high sulfate treatments (520+/-73 and 613+/-80 ng/g,
      respectively). For lake chubsucker, mean total mercury concentration in fish from
      the high sulfate treatment (276+/-63 ng/g) was significantly elevated over that
      observed in the control (109+/-47 ng/g), the low sulfate treatment (122+/-42
      ng/g), and the reference population (41+/-2 ng/g). Mercury in periphyton was
      mostly inorganic as methylmercury ranged from 6.6 ng/g (dry weight) in the
      control to 9.8 ng/g in the high sulfate treatment, while total mercury
      concentrations ranged from 1147 ng/g in the control to a high of 1297 ng/g in the
      low sulfate treatment. Fish methylmercury bioaccumulation factors from sediment
      ranged from 52 to 390 and from 495 to 3059 for water. These results suggest that
      sulfate treatments add a factor of risk due to elevated production of
      methylmercury in sediment and porewater which biomagnified into small fish, and
      may potentially increase through the food web.

PMID- 15722095
TI  - Two formulations of the industrial surfactant, Toximul, differentially reduce
      mouse weight gain and hepatic glycogen in vivo during early development: effects
      of exposure to Influenza B Virus.
AB  - Previous studies demonstrated that young mice exposed chronically to industrial
      surfactant (IS) do not exhibit obvious adverse health effects, but do have
      persistently reduced body weights and compromised hepatic energy metabolism. The
      present study examined the time course of effects of two formulations of the
      Toximul (Tox) class of anionic/nonionic IS on body weights and liver glycogen (+/
      virus) during early development. Results showed that effects differed in two
      commonly used strains of mice. In CFW mice, 12 days' exposure to Tox resulted in
      retardation of weight gain that was most obvious several days after exposure
      ceased. In this strain effects were greater with Tox 3409F than with Tox MP-A and
      appeared to be reversible except when the mice were treated with both Tox 3409F
      and FluB. Weights of the CD-1 mice were not affected by either Tox treatment
      alone, but were significantly reduced on postnatal day 20 when Tox exposure had
      been combined with FluB infection. Postnatal replenishment of hepatic glycogen
      stores during the first three weeks also occurred at different rates in CFW and
      CD-1 mice. The effects of Tox (+/-FluB) on glycogen also varied with mouse strain
      and Tox formulation. In CFW mice, exposure to either formulation resulted in
      significant (55-59%) reductions in glycogen, although reductions were not evident
      until nine days after Tox exposure stopped. By contrast, hepatic glycogen in CD-1
      mice was reduced both during and after dermal exposure to Tox 3409F, whereas no
      effect was observed with Tox MP-A. Notably, the 3409F effect was reversible in
      the CD-1 mice, but reversal did not occur in mice also infected with FluB. Tox MP
      A+FluB-treated mice exhibited only a transient glycogen reduction. These results
      illustrate the importance of mouse strain and formulation specificities in
      assessing biological effects of xenobiotic surfactants. As well, they emphasize
      that chronic IS exposure can induce changes in growth and energy substrate
      availability in young mice that may not be evident unless there is a
      precipitating cofactor such as a viral infection.

PMID- 15722096
TI  - Modelling of the life cycle of Chironomus species using an energy-based model.
AB  - Little is known about the differences between the species of the genus Chironomus
      relatively to their life cycle strategies. This knowledge is however crucial to
      fully understand the response of the Chironomus community to field perturbations.
      Here, we proposed to study four Chironomus species by using an energy-based model
      to describe growth, emergence and reproduction. We used data from the literature
      for two species (Chironomus plumosus and Chironomus tentans) and data from our
      experiments for two other species (Chironomus prasinus and Chironomus riparius).
      We showed that our model is able to accurately describe the life-history
      attributes for all the species tested, which suggests that Chironomus species
      have the same fundamental characteristics (low maintenance energetic costs,
      isomorphism), which makes possible the building of a common modelling framework
      to assess effects of toxicants at individual and population level. The species
      showed a few differences relatively to the parameters of the models with possible
      consequences when assessing effects of chemicals on Chironomus community. For
      instance, due to differences in growth parameters, C. riparius population
      dynamics should be more sensitive to effects on individual growth than C.
      prasinus or C. plumosus ones.

PMID- 15722097
TI  - Acute toxicity of benzoic acids to the crustacean Daphnia magna.
AB  - The acute immobilization toxicity of benzoic acids substituted with hydroxyl
      and/or methoxyl groups on the aromatic ring was determined for the freshwater
      crustacean Daphnia magna under neutralized condition (initial pH: 7.45+/-0.05).
      Toxicity, expressed as EC50 value, varied depending largely on the number and
      position of phenolic hydroxyl groups. Especially, benzoic acids with ortho
      substituted hydroxyl groups were more toxic than benzoic acids with meta- and/or
      para-substituted hydroxyl groups. Whereas the limited data indicated that
      methoxyl substitution had relatively small and variable effects on the toxicity.
      Of the tested compounds, 2,4,6-trihydroxybenzoic acid showed the highest toxicity
      with the 48 h EC50 of 10 micromol l-1. This was 700 times as toxic as the parent
      benzoic acid (48 h EC50=7.0 mmol l-1) and about two orders of magnitude higher
      than those previously reported for monohalogenated benzoic acid derivatives in
      Daphnia. Within the subgroups based on the number of hydroxyl groups (N(OH)), the
      toxicity variations due to the position of hydroxyl groups appeared to be
      correlated with the logarithms of n-octanol/water partition coefficients
      (logPow). The toxicity of benzoic acids existing almost entirely as their ionized
      forms could be expressed as simple structure-toxicity relationships using these
      two descriptors (N(OH) and logPow).

PMID- 15722098
TI  - Toxic effect of stem bark and leaf of Euphorbia hirta plant against freshwater
      vector snail Lymnaea acuminata.
AB  - The aqueous stem bark and leaf extracts of plant Euphorbia hirta (family
      Euphorbiaceae) have potent molluscicidal activity. Sub-lethal doses (40% and 80%
      of LC50) of aqueous stem bark and leaf extracts of this plant also significantly
      (P<0.05) alter the levels of total protein, total free amino acid, nucleic acids
      (DNA and RNA) and the activity of enzyme protease and acid and alkaline
      phosphatase in various tissues of the vector snail Lymnaea acuminata in time and
      dose dependent manner. Euphorbia hirta (family-Euphorbiaceae) commonly known as
      Dudhi, is a common medicinal plant of India, which is used in variety of diseases
      i.e. cough, asthma, colic, dysentery, genito urinary diseases.

PMID- 15722099
TI  - Bioaccumulation of 14C-17alpha-ethinylestradiol by the aquatic oligochaete
      Lumbriculus variegatus in spiked artificial sediment.
AB  - A bioaccumulation study was performed with the endobenthic freshwater oligochaete
      Lumbriculus variegatus MULLER exposed to the radiolabelled synthetic steroid
      17alpha-ethinylestradiol (14C-EE2) in a spiked artificial sediment. Concentration
      of total radioactivity increased constantly and almost linearly during 35 days of
      exposure. The accumulation factor normalised to worm lipid content and sediment
      TOC (AFlipid/OC) was 75 at the end of the uptake period, but a steady state was
      not reached. Uptake kinetics were calculated fitting the measured AFs to a
      kinetic rate equation for constant uptake from sediment using iterative non
      linear regression analysis. After 10 days of elimination in contaminant-free
      sediment 50% of the accumulated total radioactivity was excreted by the worms.
      Extracts from L. variegatus sampled at the end of the uptake phase were analysed
      by thin layer chromatography (TLC). The results showed that 6% of the total
      radioactivity incorporated by the worms was 14C-EE2. After treatment of extracts
      with beta-glucuronidase the amount of 14C-EE2 increased to 84%. These results
      suggest that L. variegatus has the potency to accumulate high amounts of
      conjugated EE2. Hence, a transfer of EE2 to benthivores and subsequent secondary
      poisoning of predators might be possible.

PMID- 15722100
TI  - Biomarker responses and reproductive toxicity of the effluent from a Chinese
      large sewage treatment plant in Japanese medaka (Oryzias latipes).
AB  - The present study was conducted to assess the potential toxicity of the effluent
      from a large sewage treatment plant (GBD-STP) in Beijing. Japanese medakas
      (Oryzias latipes) at reproduction active period were exposed to a serial of
      graded concentrations of the effluent or 100 ng l-1 of 17-alpha-ethinylestradiol
      (EE2, positive control). Growth, gonadosomatic index (GSI), hepatosomatic index
      (HSI), reproductive success, induction potency of vitellogenin (VTG) in male fish
      and that of 7-ethoxyresorufin-o-deethylase activity (EROD) in male fish liver
      were used as test endpoints. The growth suppression of fish was observed in a
      dose-dependent manner, resulting in significant differences in both body length
      and body weight of medaka above 5% effluent. This effluent can inhibit the growth
      of gonad of medakas and are more sensitive to male than to female. At exposure
      concentration of 40% and higher, there was an unexpected decrease of HSI values,
      which may be resulted from sub-lethal toxicity of effluent to fish liver. VTG of
      plasma in males were induced in all exposure concentration levels, but not in a
      dose-dependent manner. The concentration of 5% effluent would be the lowest
      observed adverse effect level (LOAEL) affecting reproductive success when
      examining fertile individuals, fecundity and fertilization rate. The overt CYP1A
      response and higher reproductive toxicity may be indicative of low process
      efficiency of this STP.

PMID- 15722101
TI  - The application of bioassays as indicators of petroleum-contaminated soil
      remediation.
AB  - Bioremediation has proven successful in numerous applications to petroleum
      contaminated soils. However, questions remain as to the efficiency of
      bioremediation in lowering long-term soil toxicity. In the present study, the
      bioassays Spirotox, Microtox, Ostracodtoxkit F, umu-test with S-9 activation, and
      plant assays were applied, and compared to evaluate bioremediation processes in
      heavily petroleum contaminated soils. Six higher plant species (Secale cereale
      L., Lactuca sativa L., Zea mays L., Lepidium sativum L., Triticum vulgare L.,
      Brassica oleracea L.) were used for bioassay tests based on seed germination and
      root elongation. The ecotoxicological analyses were made in DMSO/H2O and DCM/DMSO
      soil extracts. Soils were tested from two biopiles at the Czechowice oil
      refinery, Poland, that have been subjected to different bioremediation
      applications. In biopile 1 the active or engineered bioremediation process lasted
      four years, while biopile 2 was treated passively or non-engineered for eight
      months. The test species demonstrated varying sensitivity to soils from both
      biopiles. The effects on test organisms exposed to biopile 2 soils were several
      times higher compared to those in biopile 1 soils, which correlated with the soil
      contaminants concentration. Soil hydrocarbon concentrations indeed decreased an
      average of 81% in biopile 1, whereas in biopile 2 TPH/TPOC concentrations only
      decreased by 30% after eight months of bioremediation. The bioassays were
      presented to be sensitive indicators of soil quality and can be used to evaluate
      the quality of bioremediated soil. The study encourages the need to combine the
      bioassays with chemical monitoring for evaluation of the bioremediation
      effectiveness and assessing of the contaminated/remediated soils.

PMID- 15722102
TI  - Effect of Chlorella pyrenoidosa on fecal excretion and liver accumulation of
      polychlorinated dibenzo-p-dioxin in mice.
AB  - The effect of Chlorella pyrenoidosa on fecal excretion and liver accumulation of
      polychlorinated dibenzo-p-dioxin in C57BL/6N mice administered dioxin was
      examined. Mice were administered 2.2 microg of 1,2,3,4,7,8-hexachlorodibenzo-p
      dioxin (H6CDD) dissolved in corn oil once after a period of acclimatization,
      after which they were fed either a basal diet, a 10% C. pyrenoidosa diet, or a
      10% Spinach diet, for five weeks. Among mice fed the 10% C. pyrenoidosa diet,
      cumulative fecal excretion of H6CDD over the first week following administration
      was significantly greater (9.2-fold) than that observed among mice fed the basal
      diet. Moreover, excretion during the fifth week following administration of H6CDD
      was still significantly greater (3.1-fold) among mice fed the 10% C. pyrenoidosa
      diet than among mice fed the basal diet. Five weeks after administration of
      H6CDD, liver accumulation of H6CDD in mice fed the 10% C. pyrenoidosa diet was
      significantly less than that observed among mice fed either the basal diet and
      the Spinach diet (by 27.9% and 34.8%, respectively). These findings suggest that
      C. pyrenoidosa may be useful in inhibiting the absorption of dioxins via food and
      the reabsorption of dioxins stored already in the body in the intestinal tract,
      thus preventing accumulation of dioxins within the body.

PMID- 15722103
TI  - A-type nuclear lamins, progerias and other degenerative disorders.
AB  - Nuclear lamins were identified as core nuclear matrix constituents over 20 years
      ago. They have been ascribed structural roles such as maintaining nuclear
      integrity and assisting in nuclear envelope formation after mitosis, and have
      also been linked to nuclear activities including DNA replication and
      transcription. Recently, A-type lamin mutations have been linked to a variety of
      rare human diseases including muscular dystrophy, lipodystrophy, cardiomyopathy,
      neuropathy and progeroid syndromes (collectively termed laminopathies). Most
      diseases arise from dominant, missense mutations, leading to speculation as to
      how different mutations in the same gene can give rise to such a diverse set of
      diseases, some of which share little phenotypic overlap. Understanding the
      cellular dysfunctions that lead to laminopathies will almost certainly provide
      insight into specific roles of A-type lamins in nuclear organization. Here, we
      compare and contrast the LMNA mutations leading to laminopathies with emphasis on
      progerias, and discuss possible functional roles for A-type lamins in the
      maintenance of healthy tissues.

PMID- 15722104
TI  - Multiple roads to the aging phenotype: insights from the molecular dissection of
      progerias through DNA microarray analysis.

PMID- 15722105
TI  - Defects in activation of nitric oxide synthases occur during delayed angiogenesis
      in aging.
AB  - Angiogenesis, the formation of new vessels from pre-existing vasculature, is
      impaired in aging. This is due, in part, to a lack of regulatory molecules such
      as nitric oxide (NO). We wished to test the hypothesis that there are deficits in
      the pathways that mediate NO production during angiogenesis (as defined by
      fibrovascular invasion into a polyvinyl alcohol (PVA) sponge implant), in aged
      mice in comparison to young mice. Sponges were implanted subcutaneously in young
      (6-8 months old, n=11) and aged (23-25 months old, n=13) mice and sampled at 14
      and 19 days. Sections from the implants were stained with antibodies against
      vascular endothelial growth factor receptor 2 (VEGFR-2), Akt, phosphorylated Akt
      (p-Akt), endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS),
      inducible NOS (iNOS), and 3-nitrotyrosine (3-NT, a marker for nitrosylated
      proteins). Expression of VEGFR-2 was similar in the sponges of young and aged
      mice. Moreover, there were no significant differences in levels of Akt or its
      phosphorylated form in sponges from young and aged mice at 14 and 19 d. In marked
      contrast, levels of eNOS, p-eNOS and iNOS were significantly decreased in sponges
      from aged mice relative to young mice (p<0.02 for eNOS, p-eNOS and <0.01 for iNOS
      between young and aged mice). Concomitantly, there was diminished expression of 3
      NT in the sponges from aged mice (p<0.05). Our data indicate that defects in the
      activation of nitric oxide synthases result in decreased NO production in aged
      tissues relative to young tissues. We propose that the subsequent lack of NO
      contributes to impaired angiogenesis in aging.

PMID- 15722106
TI  - Normal human oral keratinocytes demonstrate abnormal DNA end joining activity
      during replicative senescence.
AB  - Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of
      cellular genetic integrity. DSBs are repaired by cellular end joining activity,
      which could proceed with varying degrees of accuracy. Abnormal end joining may
      lead to an accumulation of mutations and contribute to genetic instability and
      cellular aging. In the present study, we compared the efficiency and accuracy of
      end joining activities in exponentially replicating and senescing normal human
      oral keratinocytes (NHOK). We developed an in vitro end joining assay utilizing a
      plasmid linearized with a unique EcoR I or EcoR V restriction site. The
      efficiency of end joining was determined by PCR with primers that could amplify
      the fragment containing the end joining site. The accuracy of end joining was
      assessed by determining whether the original EcoR I site was restored after end
      joining. Both replicating and senescing cultures of NHOK yielded a similar level
      of end joining efficiency, which was noted by the similar intensity of PCR
      amplification. However, the frequency of end joining errors was significantly
      elevated in NHOK during replicative senescence. Senescing NHOK could thus
      accumulate abnormal end joining products, which might contribute to cellular
      aging and cancer.

PMID- 15722107
TI  - Imminent approaches towards molecular interventions in ageing.
AB  - Ageing is an innate feature of living organisms. Sensational progress in its
      molecular understanding in the last decade has culminated into a highly complex
      picture. Emerging from this complexity are the distinctive roles of some of the
      tumor suppressor pathways including p53 and pRB in maintenance of senescence
      phenotype, and telomere maintaining pathways in its escape. We discuss here the
      current scenario of molecular ageing and the use of modern approaches for its
      intervention in culture system, at least. Many of the tools we describe here are
      the newly emergent functional RNA tools that are proved to be fruitful in
      decoding the human genome. These post-genomic technologies will help us in the
      discovery of gene targets for interventions aiming to improve the quality at
      later years of life beyond their mere algebraic extension.

PMID- 15722108
TI  - Genes determining yeast replicative life span in a long-lived genetic background.
AB  - Here we describe the replicative life spans of more than 50 congenic
      Saccharomyces cerevisiae strains, each carrying a mutation previously implicated
      in yeast aging. This analysis provides a direct comparison, in a single, long
      lived strain background, of a majority of reported yeast aging genes. Of the
      eleven deletion mutations previously reported to increase yeast life span, we
      find that deletion of FOB1, deletion of SCH9, and deletion of GPA2, GPR1, or HXK2
      (three genetic models of calorie restriction) significantly enhanced longevity.
      In addition, over-expression of SIR2 or growth on low glucose increased life
      span. These results define a limited number of genes likely to regulate
      replicative life span in a strain-independent manner, and create a basis for
      future epistasis analysis to determine genetic pathways of aging.

PMID- 15722109
TI  - Due to reverse electron transfer, mitochondrial H2O2 release increases with age
      in human vastus lateralis muscle although oxidative capacity is preserved.
AB  - Age-related changes in mitochondrial H2O2 release (MHR) could be responsible for
      an increase in oxidative stress in skeletal muscle and participate in the
      development of sarcopenia. We compared MHR in vastus lateralis biopsies obtained
      from young (23.5+/-2.0 year, n=6) and elderly (67.3+/-1.5 year, n=6) healthy
      sedentary men. Isolated mitochondria were incubated in the presence of
      glutamate/malate/succinate, with or without rotenone. Muscle fat oxidative
      capacity, citrate synthase, complex II, complex III, and cytochrome c oxidase
      activities were also measured. In parallel, we analyzed in gastrocnemius of young
      male Wistar rats (n=6), the impact of lidocaine (local anesthetic used in humans)
      on mitochondrial respiration and MHR. In humans, muscle oxidative capacity was
      preserved with age but muscle MHR was markedly enhanced in elderly subjects
      compared to young adults (+175%, P<0.05). Rotenone abolished this increase,
      demonstrating that it was due to a free radical release during reverse electron
      transfer from complex II towards complex I. Lidocaine can interfere with MHR
      measurements (intra-muscular injection in rats) but it can be avoided by
      minimizing contact with muscle (small multiple subcutaneous injections in
      humans). Physiologic consequences of the observed increase in muscle MHR with
      aging remain to be determined.

PMID- 15722110
TI  - RPE65 gene mutation prevents development of autofluorescence in retinal pigment
      epithelial phagosomes.
AB  - During senescence, autofluorescent lysosomal storage bodies known as lipofusin or
      age pigment accumulate in many post-mitotic types of cells. Among these cell
      types is the retinal pigment epithelium (RPE) of the mammalian eye. The
      mechanisms of lipofuscin formation and accumulation have been studied more
      extensively in the RPE than in any other cell type. Substantial evidence
      indicates that Vitamin A derivatives (retinoids) are required for RPE lipofuscin
      formation. The RPE and adjacent retina contain retinoids in the forms of retinol,
      retinyl esters, and retinaldehyde. Previous research has demonstrated that
      retinaldehydes are directly involved in the formation of one RPE lipofuscin
      fluorophore. However, RPE lipofuscin contains many other fluorophores. It has not
      been determined which retinoids are involved in the formation of these
      fluorescent compounds. Mice with a mutation in the Rpe65 gene contain substantial
      levels of retinol and retinyl esters in the RPE, but little if any retinaldehydes
      in either the RPE or retina. Therefore, these mice could be used to determine
      whether retinaldehydes are required for formation of all of the RPE lipofuscin
      fluorophores. Normal mice were given intraocular injections of a protease
      inhibitor, which resulted in the rapid accumulation in the RPE of lipofuscin-like
      inclusions. These inclusions exhibited fluorescence properties typical of RPE
      lipofuscin. Rpe65-/- mice treated with the protease inhibitor also accumulated
      inclusions similar to those observed in the normal mice. However, these
      inclusions did not fluoresce under the conditions used to visualize lipofuscin
      fluorescence. These findings indicate that the aldehyde form of Vitamin A is
      required for the formation of not only one, but all of the RPE lipofuscin
      fluorophores.

PMID- 15722111
TI  - Developmental decrease in rat small intestinal creatine uptake.
AB  - Phosphocreatine is an energy buffer and transducer in the heart, the brain and
      the skeletal muscle. Recently, we have demonstrated the presence of the Na+/Cl
      /creatine transporter at the apical membrane of the small intestinal epithelium.
      Herein the ontogeny and segmental distribution of rat intestinal creatine
      transport activity are investigated. [14C]-Creatine uptake was measured in the
      jejunum and ileum of 16 day gestation foetuses, newborn, suckling, weaning, 1-, 2
      , 7- and 12-month-old (adult) rats. Creatine content in amniotic fluid, in rat
      and commercial milk and in rat chow, was measured by HPLC. NaCl-dependent
      creatine uptake was maximal in newborn rats and, in all the ages tested, higher
      in the ileum than in the jejunum. In the latter, NaCl-dependent creatine uptake
      was undetectable after weaning. Kinetic studies revealed that the jejunum and
      ileum have the same creatine uptake system, and that maturation decreases its
      Vmax but not the apparent Km. Maintenance of the pups on a commercial milk diet
      supplemented with creatine prevented the ileal periweaning decline in creatine
      uptake activity, but not that in the jejunum. In 1-month-old rats,
      supplementation with creatine increased ileal, but not jejunal, creatine uptake.
      The results demonstrate for the first time that: (i) creatine uptake along the
      length of the small intestine is mediated by the same transport system, (ii) the
      activity of this transport system changes in a specific manner with maturation
      and (iii) these changes appear to be genetically programmed and controlled by the
      intestinal creatine content.

PMID- 15722113
TI  - The basics about nitric oxide.
AB  - Nitric oxide is a gas and a free radical which is now recognised to have very
      important physiological roles. It is synthesised enzymatically from the amino
      acid L-arginine in a number of tissues using the three isoforms of nitric oxide
      synthase, one of which is inducible and can form much large amounts of NO. NO is
      important in the endothelium-dependent regulation of blood flow and pressure as
      well as inhibiting the activation of blood platelets. NO is recognised as a
      neurotransmitter at least in certain types of nerves. Along with other free
      radicals, NO is also important in the primary defence mechanisms against attack
      by micro-organisms. NO has a close interaction with iron-containing proteins and
      binds to haem. By this process NO activates a haem-containing enzyme called
      soluble guanylyl cyclase which is activated a thousand fold to produce the
      signalling molecule cyclic GMP. This has many effects at the molecular level to
      set in train the pathways which propagate the diverse physiological actions of
      NO. Although this pathway through cyclic GMP is important, this is by no means
      the only mechanism by which NO influences the activities of the cell. These
      alternative pathways depend on modification of the structure of enzymes and
      structural proteins in several different ways. Most of these modifications result
      from the actions of NO with other free radicals such as oxygen and superoxide
      anions to produce reactive oxidants. The oxidants modify the proteins by, among
      others, nitrosation and nitration of proteins of thiol groups and aromatic amino
      acids respectively. These changes introduce potential new subtleties to the
      effects on NO on cellular function which are only now being explored. Protein
      modifications by NO are even more evident in many inflammatory disorders and may
      account, at least to some extent, to the pathology seen in these conditions.

PMID- 15722114
TI  - The role of nitric oxide in cardiovascular diseases.
AB  - Nitric oxide (NO) is a gaseous lipophilic free radical cellular messenger
      generated by three distinct isoforms of nitric oxide synthases (NOS), neuronal
      (nNOS), inducible (iNOS) and endothelial NOS (eNOS). NO plays an important role
      in the protection against the onset and progression of cardiovascular disease.
      Cardiovascular disease is associated with a number of different disorders
      including hypercholesterolaemia, hypertension and diabetes. The underlying
      pathology for most cardiovascular diseases is atherosclerosis, which is in turn
      associated with endothelial dysfunctional. The cardioprotective roles of NO
      include regulation of blood pressure and vascular tone, inhibition of platelet
      aggregation and leukocyte adhesion, and prevention smooth muscle cell
      proliferation. Reduced bioavailability of NO is thought to be one of the central
      factors common to cardiovascular disease, although it is unclear whether this is
      a cause of, or result of, endothelial dysfunction. Disturbances in NO
      bioavailability leads to a loss of the cardio protective actions and in some case
      may even increase disease progression. In this chapter the cellular and
      biochemical mechanisms leading to reduced NO bioavailability are discussed and
      evidence for the prevalence of these mechanisms in cardiovascular disease
      evaluated.

PMID- 15722115
TI  - Nitric oxide and neurological disorders.
AB  - This article aims to give a broad overview of some of the potential targets for
      nitric oxide (NO) in the brain. The relevance of NO in both physiological and
      pathological scenarios is considerable. There is substantial evidence that
      neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease,
      involve NO in their pathogenesis. Here we describe a number of cellular
      components which may be affected by NO, with particular relevance to neurological
      diseases. As the mitochondrion (in particular the electron transport chain) would
      appear to be of importance when considering the deleterious effects of NO, this
      review has a particular emphasis on that organelle. Cellular and mitochondrial
      antioxidants such as glutathione and ubiquinone are also discussed. In addition,
      the pivotal role of the astrocyte in both neuroprotection or neurodegeneration
      are examined.

PMID- 15722116
TI  - Application of pharmaceuticals to nitric oxide.
AB  - Nitric oxide (NO) is an important and widespread physiological mediator. Both
      excess tissue NO and its deficiency have been implicated in the development of
      several disease states. It is therefore of great therapeutic value that
      appropriate pharmacological treatments are made available to either promote or
      inhibit NO production. This review will focus on the main areas of pharmaceutical
      development and application; these include the different types of NO donor
      treatments currently in use, inhibition of nitric oxide synthase and gene
      therapy. Furthermore, the recent pharmaceutical developments for the promotion of
      NO production and the problems associated with NO inhibitors will also be
      discussed. During the next few years it will become apparent whether manipulation
      of NO has multiple therapeutic applications or whether the diversity of effects
      renders intervention too non-specific.

PMID- 15722118
TI  - Degradable thiol-acrylate photopolymers: polymerization and degradation behavior
      of an in situ forming biomaterial.
AB  - Degradable thiol-acrylate photopolymers are a new class of biomaterials capable
      of rapidly polymerizing under physiological conditions upon exposure to UV light,
      with or without added photoinitiators, and to depths exceeding 10 cm. These
      materials are formed in situ, and the versatility of their chemistry affords a
      high degree of control over the final material properties. For example,
      variations in monomer mole fractions directly affect the final network molecular
      structure, varying the time required to achieve complete mass loss from 25 to 100
      days, the molecular weight distributions of the degradation products, and the
      swelling ratios and compressive moduli throughout degradation. Additionally,
      varying the mole fraction of multifunctional thiol monomer in the initial
      reaction mixture controls the concentration of reactive sites in the network
      available for post-polymerization modification of the polymer.

PMID- 15722119
TI  - Effect of synthetic peptides on osteoblast adhesion.
AB  - The quality of the early cell/material interactions is responsible for the long
      term functional properties of any implanted device. Accordingly, "next
      generation" dental/orthopedic biomaterials should be able to promote osteoblast
      adhesion thus improving the integration process between surgically placed
      implants and biological tissues. Recent studies have identified a wide range of
      biochemical signals that can be exploited to promote adhesion, migration,
      proliferation and differentiation of cells. The clinical use of natural factors
      to promote osteoblast adhesion is complicated because those are often insoluble
      and unstable macromolecules and, in addition, it is difficult to obtain them in
      high quantities, with good purity grade and at low cost. A valid alternative
      could be the use of short peptides carrying the minimum active sequence of the
      natural macromolecular factor. This paper describes the properties of two classes
      of peptides, promoting different adhesion mechanisms, to enhance rat bone marrow
      osteoblast adhesion both to polystyrene and to acellular bone matrix.

PMID- 15722120
TI  - Influence of nanoporous alumina membranes on long-term osteoblast response.
AB  - A major goal of bone tissue engineering is to design better scaffold
      configuration and materials to better control osteoblast behavior. Nanoporous
      architecture has been shown to significantly affect cellular response. In this
      work, nanoporous alumina membranes were fabricated by a two-step anodization
      method to investigate bone cell response. Osteoblasts were seeded on nanoporous
      alumina membranes to investigate both short-term adhesion and proliferation and
      long-term functionality and matrix production. Cell adhesion and proliferation
      were characterized using a standard MTT assay and cell counting. The total
      protein content was measured after cell lysis using the BCA assay. Matrix
      production was characterized in terms of surface concentrations of calcium and
      phosphorous, components of bone matrix, using X-ray photoelectron spectroscopy
      (XPS). The results from nanoporous alumina membranes were compared with those of
      amorphous alumina, aluminum, commercially available ANOPORE and glass. Results
      indicate improved osteoblast adhesion and proliferation and increased matrix
      production after 4 weeks of study.

PMID- 15722121
TI  - Myoblast proliferation and differentiation on fibronectin-coated self assembled
      monolayers presenting different surface chemistries.
AB  - Biomaterial surface properties modulate protein adsorption and cell adhesion to
      elicit diverse cellular responses in biomedical and biotechnological
      applications. We used alkanethiol self-assembled monolayers presenting well
      defined chemistries (OH, CH(3), NH(2), and COOH) to analyze the effects of
      surface chemistry on myoblast proliferation and differentiation. Surfaces were
      pre-coated with equivalent densities of fibronectin. C2C12 skeletal myoblasts
      exhibited surface-dependent differences in cell proliferation (COOH = NH(2) >
      CH(3) = OH). Myogenin and troponin T gene expression levels were up-regulated on
      CH(3) and OH surfaces compared to other chemistries. Furthermore, immunostaining
      for sarcomeric myosin revealed surface chemistry-dependent differences in
      myogenic differentiation following the pattern OH > CH(3) > NH(2) = COOH.
      Immunostaining analyses of integrin subunits demonstrated surface chemistry
      dependent differences in integrin binding to adsorbed fibronectin. OH and CH(3)
      surfaces supported selective binding of alpha(5)beta(1) integrin while the COOH
      and NH(2) functionalities displayed binding of both alpha(5)beta(1) and
      alpha(V)beta(3) Myogenic differentiation correlated with differences in integrin
      binding; surface chemistries that supported selective binding of alpha(5)beta(1)
      displayed enhanced differentiation. Finally, blocking beta(1), but not beta(3),
      integrins inhibited differentiation, implicating specific integrins in the
      differentiation process. These results demonstrate that surface chemistry
      modulates myoblast proliferation and differentiation via differences in integrin
      binding to adsorbed fibronectin.

PMID- 15722122
TI  - Cytotoxicity of three-dimensionally ordered macroporous sol-gel bioactive glass
      (3DOM-BG).
AB  - In this study, 80% SiO(2)-20% CaO (mole fraction) three-dimensionally ordered
      macroporous sol-gel bioactive glass (3DOM-BG, average pore size: 345 nm)
      particles were prepared and characterized. Since the 3DOM-BGs have a novel
      microstructure and ion-releasing profile, the cytotoxicity of 3DOM-BG particles
      was tested. The cytotoxicity tests were performed using MC3T3-E1 osteoblast-like
      cells: (1) Wst-1 assay for cell viability after culture in extracts from 3DOM-BG
      particles; (2) phase contrast microscopy for cell morphology after culture with
      3DOM-BG particles; and (3) fluorescence microscopy for imaging cells cultured
      directly on 3DOM-BG particles. The results showed that 3DOM-BG particles were not
      cytotoxic, and that cells attached, spread and proliferated on and around 3DOM-BG
      particles.

PMID- 15722123
TI  - Long-term maintenance of human articular cartilage in culture for biomaterial
      testing.
AB  - Cartilage is a tissue that derives its unique mechanical and biological
      properties from the combination of relatively few cells and a large amount of a
      complex extracellular matrix. Furthermore, cartilage tissue is comparatively slow
      to respond to changes or harmful influences. To date, the optimal generation and
      long-term maintenance of cultured human articular cartilage for in vitro testing
      of biomaterials, poses an experimental difficulty. Experiments using cultured
      isolated chondrocytes in combination with scaffolds often fail to yield results
      comparable to the in-vivo situation. Consequently, our aim was to develop a
      culture method that allows in vitro maintenance of human hyaline cartilage
      explants in an optimal quality over an extended period of time. Such a culture
      could, for example, be used to determine the long-term effect of a new scaffold
      on intact cartilage, as an in vitro model for repair processes and to investigate
      biomaterial integration. In this study we compared conventional static cultures
      with and without serum supplementation to a serum-free perfusion culture for the
      ability to maintain human articular cartilage explants in a morphologically
      intact and differentiated state over an extended period of time of up to 56 days.
      Results were evaluated and compared by morphological, histochemical and
      immunohistochemical methods. The experiments showed that short-term maintenance
      of cartilage in a differentiated state for up to 14 days is possible under all
      culture conditions tested. However, best long-term culture results for up to 56
      days were obtained with perfusion culture under serum-free conditions. Such a
      perfusion culture system can be used to perform biocompatabilty tests in vitro by
      long-term coculture of biomaterial and intact human articular cartilage.

PMID- 15722124
TI  - Neovascularization and bone regeneration by implantation of autologous bone
      marrow mononuclear cells.
AB  - We examined whether transplantation of autologous bone marrow mononuclear cells
      (BM-MNCs) can augment neovascularization and bone regeneration of bone marrow in
      femoral bone defects of rabbits. Gelatin microspheres containing basic fibroblast
      growth factor (bFGF) were prepared for the controlled release of bFGF. To
      evaluate the in vivo effect of implanted BM-MNCs, we created bone defects in the
      rabbit medial femoral condyle, and implanted into them 5 x 10(6) fluorescent
      labeled autologous BM-MNCs together with gelatin microspheres containing 10
      microg bFGF on an atelocollagen gel scaffold. The four experimental groups, which
      were Atelocollagen gel (Col), Col + 5 x 10(6) BM-MNCs, Col + 10 microg bFGF, and
      Col + 5 x 10(6) BM-MNCs + 10 microg bFGF, were implanted into the sites of the
      prepared defects using Atelocollagen gel as a scaffold. The autologous BM-MNCs
      expressed CD31, an endothelial lineage cell marker, and induced efficient
      neovascularization at the implanted site 2 weeks after implantation. Capillary
      density in Col + BM-MNCs + bFGF was significantly large compared with other
      groups. This combination also enhanced regeneration of the bone defect after 8
      weeks to a significantly greater extent than either BM-MNCs or bFGF on their own.
      In summary, these findings demonstrate that a combination of BM-MNCs and bFGF
      gelatin hydrogel enhance the neovascularization and the osteoinductive ability,
      resulting in bone regeneration.

PMID- 15722125
TI  - The use of temperature-composition combinatorial libraries to study the effects
      of biodegradable polymer blend surfaces on vascular cells.
AB  - Controlling cellular and physiological responses such as adhesion, proliferation
      and migration is a highly desirable feature of engineered scaffolds. One
      important application would be the design of tissue engineered vascular grafts
      that regulate cell adhesion and growth. We utilized temperature-composition
      combinatorial polymer libraries to investigate the effects of surfaces of blended
      poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(epsilon-caprolactone) (PCL) on
      murine vascular smooth muscle cells (SMC). In this manner, SMCs were exposed to
      approximately 1000 distinguishable surfaces in a single experiment, allowing the
      discovery of optimal polymer compositions and processing conditions. SMC
      adhesion, aggregation, proliferation, and protein production were highest in
      regions with mid- to high-PCL concentrations and high annealing temperatures.
      These regions exhibited increased surface roughness, increased microscale PLGA
      rich matrix stiffness, and significant change of bulk PCL-rich crystallinity
      relative to other library regions. This study revealed a previously unknown
      processing temperature and blending composition for two well-known polymers that
      optimized SMC interactions.

PMID- 15722126
TI  - Endothelial cell--interactions with polyelectrolyte multilayer films.
AB  - The seeding of endothelial cells (ECs) on biomaterial surfaces became a major
      challenge, allowing to improve the non-thrombogenic properties of these surfaces.
      Recently, the use of polyelectrolyte films has been suggested as a new versatile
      technique of surface modification aimed at tissue engineering. In this study, we
      evaluate the adhesion properties of ECs on two types of polyelectrolyte films
      ending either by poly(D-lysine) (PDL), or poly(allylamine hydrochloride) (PAH),
      and compared them to data obtained on PDL or PAH monolayers, glass and
      fibronectin (Fn)-coated glass. ECs seeded on polyelectrolyte films showed a good
      morphology, allowing ECs to resist physiological shear stress better compared to
      ECs seeded on glass or Fn. The expression of beta1 integrins was slightly lower
      on polyelectrolyte films than on control surfaces. However, the phosphorylation
      of focal adhesion kinase, involved in the transduction of adhesion signal, was
      not modified on PAH ending films compared to control surfaces; whereas it became
      lower on PDL ending films. Finally, PAH ending films improve strongly ECs
      adhesion without disturbing the adhesion mechanism, necessary for the development
      of a new endothelium. These types of films or similar build-ups could thus be
      used in the future as a way to modify surfaces for vascular tissue engineering.

PMID- 15722127
TI  - Cell adhesive PET membranes by surface grafting of RGD peptidomimetics.
AB  - A non-peptide mimic of the Arg-Gly Asp (RGD) active sequence of adhesive proteins
      (such as vitronectin) has been equipped with two different spacer-arms for
      surface anchorage. The covalent grafting on poly(ethylene terephthalate) (PET)
      membrane was realized via the activation of the hydroxyl polymer chain-ends by
      tosylation followed by nucleophilic substitution. The surface density of
      peptidomimetics was determined by X-ray photoelectron spectroscopy (XPS), on the
      basis of F/C atomic ratios since a fluorine tag was incorporated into the RGD
      like compounds. The biological activity of soluble peptidomimetics was evaluated
      versus isolated human integrin alpha(v)beta(3) (vitronectin receptor), and versus
      CaCo2 cells. Inhibition of cellular adhesion was observed after pre-incubation of
      CaCo2 cells with soluble peptidomimetics. On the other hand a significant
      promotion of cellular adhesion resulted from the surface grafting of
      peptidomimetics on the PET culture substrate. The best performance was obtained
      with the RGD-like integrin ligand bearing a triethylene glycol spacer-arm.

PMID- 15722128
TI  - Cultivation of endothelial cells on adhesive protein-free synthetic polymer gels.
AB  - Various hydrogels without modification by any cell adhesive proteins have been
      investigated as cell scaffolds. The present study shows that bovine fetal aorta
      endothelial cells can adhere, spread, proliferate, and reach confluence on
      poly(acrylic acid), poly(sodium p-styrene sulfonate), and poly(2-acrylamido-2-
      methyl-1-propanesulfonic sodium) gels, whereas cells reach subconfluence on
      poly(vinyl alcohol) and poly(methacrylic acid) gels. The proliferation behavior
      was sensitive to both hydrogel charge density and crosslinker concentration. The
      relationship between cell proliferation and zeta potential of gels was discussed.
      It was found that hydrogels with a negative zeta potential higher than about 20
      mV facilitates cell proliferation.

PMID- 15722129
TI  - 3D femtosecond laser patterning of collagen for directed cell attachment.
AB  - Three-dimensional micropatterned collagen scaffolds were fabricated by
      femtosecond laser ablation. An 800 nm, 45 fs Ti:Sapphire laser was used to create
      various 3D patterns in a collagen gel, including holes, lines and grids. An
      optimal collagen concentration was found for both substrate patterning and cell
      compatibility. The threshold fluence for ablation of the scaffold was found to be
      0.0 6 J/cm(2), and the morphology of the ablation craters was measured as a
      function of fluence. Mesenchymal stem cells from rat bone marrow and human
      fibroblasts were seeded within the ablated patterns and were shown to be viable
      for at least 10 days.

PMID- 15722130
TI  - Electrospun degradable polyesterurethane membranes: potential scaffolds for
      skeletal muscle tissue engineering.
AB  - Skeletal muscle tissue engineering represents an attractive approach to overcome
      problems associated with autologous transfer of muscle tissue and provides a
      valid alternative in muscle regeneration enhancement. The aim of this study was
      to investigate the suitability, as scaffold for skeletal muscle tissue
      engineering, of a known biodegradable block copolymer (DegraPol) processed by
      electrospinning in the novel form of microfibrous membranes. Scaffolds were
      characterized with reference to their morphological, degradative and mechanical
      properties. Subsequently, cell viability, adhesion and differentiation on coated
      and uncoated DegraPol) slides were investigated using line cells (C2C12 and L6)
      and primary human satellite cells (HSCs). The membranes exhibited absence of
      toxic residuals and satisfactory mechanical properties (linear elastic behavior
      up to 10% deformation, E modulus in the order of magnitude of MPa). A promising
      cellular response was also found in preliminary experiments: both line cells and
      HSCs adhered, proliferated and fused on differently coated electrospun membranes.
      Positive staining for myosin heavy chain expression indicated that
      differentiation of C2C12 multinucleated cells occurred within the porous
      elastomeric substrate. Together the results of this study provide significant
      evidence of the suitability of electrospun DegraPol) membranes as scaffolds for
      skeletal muscle tissue engineering and that they represent a promising
      alternative to scaffolds currently used in this field.

PMID- 15722131
TI  - In vivo degradation of porous poly(propylene fumarate)/poly(DL-lactic-co-glycolic
      acid) composite scaffolds.
AB  - This study investigated the in vivo degradation of poly(propylene fumarate)
      (PPF)/poly(DL-lactic-co-glycolic acid) (PLGA) composite scaffolds designed for
      controlled release of osteogenic factors. PPF/PLGA composites were implanted into
      15.0mm segmental defects in the rabbit radius, harvested after 12 and 18 weeks,
      and analyzed using histological techniques to assess the extent of polymer
      degradation as well as the tissue response within the pores of the scaffolds.
      Polymer degradation was limited to micro-fragmentation of the scaffold at the
      ends and edges of the implant at both 12 and 18 weeks. The tissue within the
      pores of the scaffold consisted of fibrous tissue, blood vessels and some
      inflammatory cells. In areas where polymer breakdown was evident, an increased
      inflammatory response was observed. In contrast, areas of bone ingrowth into the
      polymer scaffold were characterized by minimal inflammatory response and polymer
      degradation. Our results show that minimal degradation of porous PPF occurs
      within 18 weeks of implantation in a rabbit model. Further, the in vivo
      degradation data of porous PPF/PLGA scaffolds are comparable with earlier
      obtained in vitro data.

PMID- 15722132
TI  - Chitin-based tubes for tissue engineering in the nervous system.
AB  - The purpose of this study was to investigate chitin and chitosan as potential
      materials for biodegradable nerve guides. Transparent chitin hydrogel tubes were
      synthesized, for the first time, from chitosan solutions using acylation
      chemistry and mold casting techniques. Alkaline hydrolysis of chitin tubes
      resulted in chitosan tubes, with the extent of hydrolysis controlling the
      resulting amine content. This, in turn, impacted compressive strength and cell
      adhesion. Chitosan tubes were mechanically stronger than their chitin origins, as
      measured by the transverse compressive test, where tubes having degrees of
      acetylation of 1%, 3%, 18% (i.e. chitosan) and 94% (i.e. chitin) supported loads
      at a 30% displacement of 40.6 +/- 4.3, 25.3 +/- 4.5, 10.6 +/- 0.8, and 8.7 +/-
      0.4 g, respectively. However, the chitin processing methodology could be
      optimized for compressive strength, by either incorporating reinforcing coils in
      the tube wall, or air-drying the hydrogel tubes. Chitin and chitosan supported
      adhesion and differentiation of primary chick dorsal root ganglion neurons in
      vitro. Chitosan films showed significantly enhanced neurite outgrowth relative to
      chitin films, reflecting the dependence of nerve cell affinity on the amine
      content in the polysaccharide: neurites extended 1794.7 +/- 392.0 microm/mm(2) on
      chitosan films vs. 140.5 +/- 41.6 microm/mm(2) on chitin films after 2 days of
      culture. This implies that cell adhesion and neurite extension can be adjusted by
      amine content, which is important for tissue engineering in the nervous system.
      The methods for easy processing and modification of chitin and chitosan described
      herein, allow the mechanical properties and cyto-compatibility to be controlled
      and provide a means for a broader investigation into their use in biomedical
      applications.

PMID- 15722133
TI  - Effects of growth regulation on conditionally-transformed alginate-entrapped
      insulin secreting cell lines in vitro.
AB  - The ability to control cell growth is an issue of critical importance for the use
      of transformed beta-cell lines within a bioartificial pancreas. Such control can
      be achieved either by entrapping the cells in a biomaterial that can inhibit cell
      proliferation or by genetically modifying the cells to regulate growth.
      Integrating tetracycline-off or -on operon systems into murine insulinoma cell
      lines (betaTC-tet and R7T1, respectively) allows cell growth regulation upon
      exposure to tetracycline (TC) or its derivative doxycycline (Dox), respectively.
      However, the effects of this regulatory approach on the long-term phenotypic
      metabolic and secretory stability of alginate-entrapped cells have yet to be
      thoroughly investigated. In this study, cultures of betaTC-tet and R7T1 cells
      entrapped in alginate beads were allowed to grow freely, or were growth
      regulated, either at the onset, or after 20 days of growth. The data show that
      growth regulation of alginate-entrapped cells is achievable with chronic
      administration of the regulatory compound in a concentration-dependent manner.
      However, as these cultures age, the amount of insulin released does not always
      reflect the metabolic and histological characteristics of the cultures. This
      change, coupled with a loss of glucose stimulated insulin secretion in the Dox
      treated R7T1 cell line, indicate a phenotypic shift of cells with an activated
      tet-operon. These observations have implications on the selection and long-term
      function of three-dimensional bioartificial pancreatic constructs that include
      conditionally transformed beta-cell lines.

PMID- 15722135
TI  - Tissue engineered ceramic artificial joint--ex vivo osteogenic differentiation of
      patient mesenchymal cells on total ankle joints for treatment of osteoarthritis.
AB  - Total joint arthroplasty is the common treatment of severe cases of
      osteoarthritis. However, complications involving failure of the bone-prosthesis
      interface are significant, especially in ankle arthroplasty. To prevent this
      complication, we attempted a tissue engineering approach using the mesenchymal
      cells of the patient. We collected a small amount of fresh bone marrow cells from
      the patient's iliac crest and expanded the number of mesenchymal cells. We then
      applied the mesenchymal cells to a ceramic ankle prosthesis and cultured them to
      form an osteoblasts/bone matrix on the prosthesis. We used tissue engineered
      prostheses on three patients suffering from ankle arthritis and followed their
      progress for at least 2 years. Follow-up X-ray examinations revealed early
      radiodense appearance (bone formation) around the cell-seeded areas of the
      prostheses about 2 months after the operation after which a stable host bone
      prosthesis interface was established. All patients showed high clinical scores
      after the operation and did not exhibit inflammatory reactions. These preliminary
      results indicate that the tissue engineering approach using autologous cultured
      marrow mesenchymal cells might prevent aseptic loosening of the total ankle
      arthroplasty.

PMID- 15722134
TI  - A system for the direct co-culture of endothelium on smooth muscle cells.
AB  - The development of a functional, adherent endothelium is one of the major factors
      limiting the successful development of tissue engineered vascular grafts (TEVGs).
      The adhesion and function of endothelial cells (ECs) on smooth muscle cells
      (SMCs) are poorly understood. The goal of this research was to optimize
      conditions for the direct culture of endothelium on SMCs, and to develop an
      initial assessment of co-culture on EC function. The co-culture consisted of a
      culture substrate, a basal adhesion protein, a layer of porcine SMCs, a medial
      adhesion protein, and a layer of porcine ECs. Conditions that led to successful
      co-culture were: a polystyrene culture substrate, a quiescent state for SMCs,
      subconfluent density for SMC seeding and confluent density for EC seeding, and
      fibronectin (FN) for the basal adhesion protein. EC adhesion was not enhanced by
      addition of FN, collagen I, collagen IV or laminin (LN) to the medial layer. 3-D
      image reconstruction by confocal microscopy indicated that SMCs did not migrate
      over ECs and the cells were present in two distinct layers. Co-cultures could be
      consistently maintained for as long as 10 days. After exposure to 5 dyne/cm(2)
      for 7.5 h, ECs remained adherent to SMCs. PECAM staining indicated junction
      formation between ECs, but at a lower level than that observed with EC
      monocultures. Co-culturing ECs with SMCs did not change the growth rate of ECs,
      but EC DiI-Ac-LDL uptake was increased. Thus, a confluent and adherent layer of
      endothelium can be directly cultured on quiescent SMCs.

PMID- 15722136
TI  - A novel solvent-free method for the manufacture of biodegradable antibiotic
      capsules for a long-term drug release using compression sintering and ultrasonic
      welding techniques.
AB  - This report was to develop a novel solvent-free method for the manufacture of
      biodegradable capsules for a long-term drug delivery. To manufacture an
      antibiotic capsule, polylactide-polyglycolide copolymers were pre-mixed with
      vancomycin. The mixture was then injection compression molded to form a cylinder
      with a cover of 8mm in diameter. After the addition of gentamicin sulfate into
      the core, an ultrasonic welder was used to seal the capsule. An elution method
      and an high-performance liquid chromatography assay were employed to characterize
      the in vitro release rates of the antibiotics over a 30-day period. It was found
      that biodegradable capsules released high concentration of vancomycin and
      gentamicin (well above the minimum inhibition concentration) in vitro for the
      period of time needed to treat bone infection; i.e., 2-4 weeks. A bacterial
      inhibition test was carried out to determine the relative activity of the
      released antibiotics. The diameter of the sample inhibition zone ranged from 3 to
      18 mm, which is equivalent to 16.7-100% of relative activity. By adopting this
      novel technique, we will be able to manufacture biodegradable capsules of various
      medicines for long-term drug delivery.

PMID- 15722137
TI  - Reversal of silver sulfadiazine-impaired wound healing by epidermal growth
      factor.
AB  - Silver sulfadiazine (Ag-SD) is a useful antibacterial agent for wound treatment.
      However, recent findings indicate that the compound delays the wound-healing
      process. That delay may be reversed by treatment with growth factors. The purpose
      of this study, was to evaluate the cyto-protective effect of epidermal growth
      factor (EGF) against Ag-SD treated keratinocytes and to investigate the
      reversibility of the impaired wound-healing process by the co-supplementation of
      EGF. Four types of drug-loaded collagen sponge dressings with different
      concentrations of Ag-SD, EGF and Ag-SD + EGF were prepared. An immortalized
      keratinocyte, HaCaT cells, were cultured in 35-mm Petri-dish using Dulbecco's
      Modified Eagle's Minimal Essential Medium (DMEM) with 10% FBS. Cultures were
      treated with the samples submerged, and viabilities of cultures were evaluated
      using MTT assay. The wound heal efficacy was evaluated in a partial thickness
      burn mouse model. Cells treated with EGF showed a cyto-protective effect on 1% Ag
      SD treated cells with significant increase in viable cell numbers at
      concentrations ranging from 1 to 50 microg/ml. The cytotoxicity of Ag-SD impaired
      wound healing, while the addition of EGF could reverse the impairment. This
      evidence suggests that EGF is a useful agent in the retardation of wound healing
      caused by Ag-SD. Therefore, a drug delivery system containing both EGF and Ag-SD,
      such as that used in the study, may be clinically relevant.

PMID- 15722138
TI  - A novel pH- and ionic-strength-sensitive carboxy methyl dextran hydrogel.
AB  - A fast and simple method for the preparation of pH-sensitive hydrogel membranes
      for drug delivery and tissue engineering applications has been developed using
      carbodiimide chemistry. The hydrogels were formed by the intermolecular cross
      linking of carboxymethyl dextran (CM-dextran) using 1-ethyl-(3-3
      dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide
      (NHS). Infrared spectra of the hydrogels suggest the formation of ester bonds
      between the hydroxyl and carboxyl groups in the CM-dextran. The porosity of the
      hydrogels produced, as shown by protein diffusion, increases in response to
      changes in the pH and the ionic strength of the external medium. The results show
      pH-dependent swelling behaviour arising from the acidic pedant groups in the
      polymer network. The diffusion of the protein lysozyme through the hydrogel
      membranes increased with increases in both pH (5.0-9.0) and ionic strength. The
      effect of changes of pH and ionic strength on the hydrogel's permeability was
      shown to be reversible. Scanning electron microscopy of these hydrogels showed
      that pH-dependent changes in permeability are mirrored by morphological changes
      in gel structure.

PMID- 15722139
TI  - Binding specificity of alpha-bilirubin-imprinted poly(methacrylic acid-co
      ethylene glycol dimethylacrylate) toward alpha-bilirubin.
AB  - alpha-Bilirubin is an important index to determine the liver's functions.
      Poly(methacrylic acid-co-ethylene glycol dimethylacrylate) (poly(MAA-co-EGDMA))
      imprinted with alpha-bilirubin was proposed and shown to be able to bind alpha
      bilirubin specifically. The extraction condition was also discussed. Polymers
      prepared by imprinting bilirubin in poly(MAA-co-EGDMA) and in poly(beta
      cyclodextrin-co-EGDMA) were compared. In this work, binding specificity of
      molecularly imprinted polymer (MIP) toward the target template, alpha-bilirubin,
      is discussed. Adsorption profile of alpha-bilirubin by bilirubin-imprinted
      poly(MAA-co-EGDMA) was measured as a function of time, from where the equilibrium
      could be determined. Two hours was determined to be the proper time for
      adsorption. Biliverdin as a rather similar analog compound of bilirubin was
      chosen for comparison of binding specificity in this study. Progesterone as well
      as testosterone was also chosen for study because they both co-exist in serum
      with bilirubin and might interfere with binding capacity of imprinted poly(MAA-co
      EGDMA) toward alpha-bilirubin. Specificity of this polymer for bilirubin was thus
      confirmed by tasks carried out in mixture solutions comprised of compounds above.
      It is true that biliverdin contained in the binary mixture did affect the binding
      capacity of bilirubin. Nevertheless, polymer's binding specificity for bilirubin
      was essentially sufficient for recognition of alpha-bilirubin in the presence of
      other compounds. How MIP identified the target template molecule, alpha
      bilirubin, is also elucidated.

PMID- 15722140
TI  - In vitro cell culture methods for investigating Campylobacter invasion
      mechanisms.
AB  - Studying the mechanisms of Campylobacter pathogenesis is complicated by the lack
      of simple animal models that mimic the disease seen in humans. In vitro cell
      culture methods provide a useful alternative to investigate the interactions
      between Campylobacter and the host epithelium that occur during infection. In the
      genomics era there is an increasing use of in vitro cell culture techniques to
      interrogate the potential role of different genes in pathogenesis. The aim of
      this review was to discuss the suitability and limitations of the various
      experimental approaches that might be adopted. We review current knowledge
      concerning the influence of cell-specific as well as bacterial factors required
      for Campylobacter invasion such as flagella and secreted proteins. The
      involvement and effects of phase variation on the results of invasion studies in
      cell culture emphasise the need to verify observed strain variations. We present
      the use of a mathematical Invasion Success Model to analyse Campylobacter
      invasion and show that it can be used to derive three strain dependent
      characteristics Imax, k, and I0. Even by combining data from independent
      experiments the Invasion Success Model can be used to statistically compare
      Campylobacter strains for their invasion of epithelial cells. Recommendations are
      given for the adoption of standard assay parameters and analytical methods such
      as the Invasion Success Model in order to facilitate comparison of data generated
      in different laboratories.

PMID- 15722142
TI  - Development of a rapid colorimetric time-kill assay for determining the in vitro
      activity of ceftazidime and tobramycin in combination against Pseudomonas
      aeruginosa.
AB  - It is standard clinical practice to use a combination of two or more
      antimicrobial agents to treat an infection caused by Pseudomonas aeruginosa. The
      antibiotic combinations are usually selected empirically with methods to
      determine the antimicrobial effect of the combination such as the time-kill assay
      rarely used as they are time-consuming and labour intensive to perform. Here, we
      report a modified time-kill assay, based on the reduction of the tetrazolium
      salt, 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide
      (XTT), that allows simple, inexpensive and more rapid determination of the in
      vitro activity of antibiotic combinations against P. aeruginosa. The assay was
      used to determine the in vitro activity of ceftazidime and tobramycin in
      combination against P. aeruginosa isolates from cystic fibrosis patients and the
      results obtained compared with those from conventional viable count time-kill
      assays. There was good agreement in interpretation of results obtained by the XTT
      and conventional viable count assays, with similar growth curves apparent and the
      most effective concentration combinations determined by both methods identical
      for all isolates tested. The XTT assay clearly indicated whether an antibiotic
      combination had a synergistic, indifferent or antagonistic effect and could,
      therefore, provide a useful method for rapidly determining the activity of a
      large number of antibiotic combinations against clinical isolates.

PMID- 15722141
TI  - Non-disruptive, real-time analyses of the metabolic status and viability of
      Streptococcus mutans cells in response to antimicrobial treatments.
AB  - Streptococcus mutans is one of a small number of recognized pathogens that lives
      among the hundreds of other bacterial species which comprise the oral flora. The
      virulence of this organism is intimately associated with its ability to live as
      an attached biofilm community on the tooth surface, and consequently, there is a
      great interest in its biofilm lifestyle. Currently, there are no established
      protocols that facilitate drug screening against this organism while it is
      entrenched in the biofilm. Furthermore, greater complications arise when
      attempting to perform these experiments in a multi-species setting. In an effort
      to circumvent these problems, we developed a quick, real-time, and non-disruptive
      method to probe the metabolic status of S. mutans growing as either a planktonic
      culture or a biofilm community. This assay takes advantage of the proven utility
      of luciferase measurements for drug screening. We placed the luciferase gene
      under the control of the S. mutans lactate dehydrogenase promoter (ldh) and
      integrated the construct onto its native position on the chromosome. We found
      this construct to be both highly expressed (<10000 cells easily detectable) and
      insensitive to many different growth parameters. When testing this reporter in
      both planktonic and biofilm cultures receiving either bacteriostatic or
      bactericidal antibiotics, we found the ldh-luc reporter to be a very accurate
      measurement of cell viability. Furthermore, we also demonstrated that this assay
      can generate useful information about the characteristics of intoxication caused
      by antibiotic activity. In addition, we modified the biofilm assay into the 96
      well format and demonstrated the feasibility of high throughput drug screening of
      biofilm embedded S. mutans.

PMID- 15722143
TI  - The effect of broth media on pneumococcal growth and the latex serotyping result.
AB  - The aim was to test Todd-Hewitt broths (TH-broths) for the ability to propagate
      pneumococci and thereafter to evaluate the serotyping result obtained by the
      Pneumotest-Latex kit (SSI). TH-broths from four different producers (Oxoid,
      Sigma, Difco, and SSI) were tested and compared separately and with Serum broth
      (SSI). Twenty-three pneumococcal strains (different serotypes) were inoculated
      into the broths with start inoculums of 10(1), 10(3), and 10(6) CFU/ml. After
      incubation, overnight viable bacterial counts and visible growth were recorded.
      All pneumococci were serotyped with the Pneumotest-Latex kit. After incubation,
      the bacterial counts in all TH-broths were within the range of log 4.65-log 7.76
      CFU/ml, while Serum broth showed an average growth ranging from log 8.05-log 8.90
      CFU/ml. Comparing the growth of the four TH-broths showed no significant
      differences. In general, Serum broth had a more pronounced visual growth than
      each of the four TH-broths. Serotyping with Serum broth showed in general
      positive and correct latex typing results for all serotypes and initial inoculum,
      while the outcome of the TH-broths showed some false negative results depending
      on inoculum and serotype. Overall the Serum broth was found to be superior to the
      four TH-broths tested both with regard to CFU/ml and when used with the
      Pneumotest-Latex kit. However, if the Pneumotest-latex kit is only used on broths
      with visible growth as stated in the instruction manual, then the differences
      between the performances of the broths from the different producers was not
      significant and all broths could be used for Pneumotest-Latex typing.

PMID- 15722144
TI  - Quantification of Enterococcus faecalis and Enterococcus faecium in different
      foods using rRNA-targeted oligonucleotide probes.
AB  - The abundance of Enterococcus faecalis and Enterococcus faecium in different
      Spanish foods was evaluated by using taxon-specific oligonucleotide probes
      targeted against extracted rRNA. Two satisfactory methods were developed for RNA
      extraction. Although the yield and purity of total RNA obtained largely depended
      on the type of food, method 1 should be recommended. The quantitative results
      obtained with the oligonucleotide probes DB6 for E. faecium and DB8 for E.
      faecalis showed that these two species accounted for less than 0.5% of the active
      microflora in all the food samples tested. These results suggest that enterococci
      form only a minor portion of the microflora of these products.

PMID- 15722145
TI  - Multicenter evaluation of mycobacteria identification by PCR restriction enzyme
      analysis in laboratories from Latin America and the Caribbean.
AB  - The identification of mycobacterial species in clinical isolates is essential for
      making patient care decisions. Polymerase chain reaction (PCR) restriction enzyme
      analysis (PRA) is a simple and rapid identification method, based on
      amplification of 441 bp of the hsp65 gene and restriction with BstEII and HaeIII.
      As a contribution to the validation of PRA, a multicenter study was performed in
      eight laboratories located in Argentina, Brazil, Colombia, Chile, and Guadeloupe.
      Each laboratory received 18 coded isolates from the collection of the Institute
      of Tropical Medicine (Antwerp, Belgium), representing duplicates of nine
      laboratory strains: Mycobacterium terrae CIPT 140320001, Mycobacterium
      scrofulaceum CIPT 140220031, Mycobacterium flavescens ATCC 14474, Mycobacterium
      triviale ATCC 23292, Mycobacterium nonchromogenicum ATCC 19530, Mycobacterium
      chitae ATCC 19627, Mycobacterium abscessus ATCC 19977, Mycobacterium kansasii
      ATCC 12478, and Mycobacterium peregrinum ATCC 14467. A detailed protocol
      including amplification, enzymatic digestion, and gel preparation was provided to
      each laboratory. Two laboratories identified correctly all 18 (100%) isolates,
      one identified correctly 17 (94.5%), two identified 14 (77.7%), one identified 11
      (61%), and two identified 8 (44.4%) isolates. Errors detected in laboratories
      with more than 77% accuracy were associated with electrophoresis running
      conditions and an unspecific amplicon produced by a single strain. Lower accuracy
      was mainly related to inappropriate use of DNA markers and insufficient training
      in interpretation of patterns. In conclusion, the PRA method was readily
      implemented in some Latin American and Caribbean laboratories of mycobacteria,
      but improvements in critical points, as gel running conditions and training in
      interpretiation of patterns, are needed in order to improve accuracy. In others,
      improvement in critical points is still necessary.

PMID- 15722146
TI  - High-density DNA probe arrays for identification of staphylococci to the species
      level.
AB  - Rapid and accurate identification and speciation of staphylococci clinical
      isolates is important for predicting medical pathology. We evaluated the ability
      of a high-density DNA probe array based on 16S rDNA sequences to identify
      Staphylococcus species. Correct identification was observed for 185 out of the
      201 strains (92%). Of the 33 tested species, the array was able to correctly
      identify 30 of them. The total time required for identification of 4 isolates was
      5 h. Such a tool represents a powerful method for routine microbiological
      diagnostic as well as for epidemiological studies.

PMID- 15722147
TI  - Immunomagnetic separation of Toxoplasma gondii oocysts using a monoclonal
      antibody directed against the oocyst wall.
AB  - Recent outbreaks of waterborne toxoplasmosis have stimulated the development of
      sensitive methods to detect Toxoplasma gondii oocysts in samples suspected to be
      contaminated. The immunomagnetic separation (IMS) have been standardised to
      detect waterborne protozoa, but it did not exist for Toxoplasma oocysts. In this
      study, we describe two monoclonal antibodies (mAbs 3G4 and 4B6) produced against
      the oocyst wall, and the incorporation of mAb 3G4 in an IMS procedure. We found
      that an indirect IMS method gave better mean recoveries than a direct one (69.4%
      and 25.2%, respectively). Dissociation of oocyst_magnetic bead complexes was
      greatly improved by using a 2% aqueous H2SO4 solution instead of a 0.1 N HCl
      solution (82.8% and 17.4%, respectively). With these parameters, mean recoveries
      of less than 1000 oocysts ranged from 44.6% to 82.9%, depending on incubating
      temperature and buffer. Age of oocysts (1 or 12 months old) does not influence
      IMS performances. Results of this study indicate that the described IMS is an
      efficient technique to recover Toxoplasma oocysts.

PMID- 15722148
TI  - Cloning and use of sC as homologous marker for Aspergillus niger transformation.
AB  - The sC sequence from Aspergillus niger was cloned and developed into a homologous
      marker system for genetic transformation. The coding region of the sC gene
      amplified by PCR from the A. niger genome was provided with Aspergillus nidulans
      expression signals (gpdA promoter and trpC terminator). This chimeric construct
      was used to successfully transform a spontaneous sC- isolate of A. niger to
      prototrophy. The transformants analyzed by Southern analysis showed integration
      of multiple copies of the transforming DNA. They also exhibited much higher ATP
      sulfurylase activity than the wild-type A. niger strain reinforcing the molecular
      data. This demonstrates the usefulness of the sCniger construct, driven by PgpdA,
      as a marker for A. niger transformation.

PMID- 15722149
TI  - Development of a versatile cassette for directional genome walking using cassette
      ligation-mediated PCR and its application in the cloning of complete lipolytic
      genes from Bacillus species.
AB  - Since the invention of the PCR technology, adaptation techniques to clone DNA
      fragments flanking the known sequence continue to be developed. We describe a
      perfectly annealed cassette available in almost unlimited quantities with
      variable sticky-and blunt-end restriction enzyme recognition sites for efficient
      restriction and ligation with the restricted target genomic DNA. The cassette
      provides a 200-bp sequence, which is used to design a variety of cassette
      specific primers. The dephosphorylation prevents cassette self-ligation and
      creates a nick at the cassette: target genome DNA ligation site suppressing
      unspecific PCR amplifications. We introduce the single-strand amplification PCR
      (SSA-PCR) technique where a lone known locus-specific primer is firstly used to
      enrich the targeted template DNA strand resulting in significant PCR product
      specificity during the second round conventional nested PCR. The distance between
      the known locus-specific primer and the nearest location of the restriction
      enzyme used determined the length of the obtained PCR product. We used this
      technique to walk downstream into the isochorismatase and upstream into the
      hypothetical conserved genes flanking the mature extracellular lipase gene from
      Bacillus licheniformis. We further demonstrated the potential of the technique as
      a cost-effective method during PCR-based prospecting for novel genes by designing
      "universal" degenerate primers that detected homologues of Family VII bacterial
      lipolytic genes in Bacillus species. The cassette ligation-mediated PCR was used
      to clone complete nucleotide sequences encoding functional lipolytic genes from
      B. licheniformis and Bacillus pumilus.

PMID- 15722150
TI  - Development of a strain-specific assay for detection of viable Lactobacillus sp.
      HOFG1 after application to cattle feed.
AB  - A strain-specific assay was developed for the detection of viable Lactobacillus
      on cattle feed. The DNA sequences of the 16S rRNA gene and four different 16S/23S
      rRNA intergenic spacer regions (ISR) from Lactobacillus sp. HOFG1 were
      determined. Based on these sequences, a strain-specific primer was designed for
      the amplification of one of the ISRs. When combined with a Lactobacillus group
      primer, the polymerase chain reaction (PCR) assay detected only Lactobacillus sp.
      HOFG1 and not other closely related L. animalis or L. murinus strains. The feed
      assay uses a combination of enrichment culturing and PCR to detect and enumerate
      viable Lactobacillus sp. HOFG1 after its application onto cattle feed. The high
      degree of primer specificity and use of selective culturing allows for the
      detection of viable Lactobacillus which is useful in tracking bacteria applied to
      complex feed mixtures that contain a high background of endogenous bacteria.

PMID- 15722151
TI  - Measurement of limestone biodeterioration using the Ca2+ binding fluorochrome
      Rhod-5N.
AB  - Limestone and marble have been used extensively in the construction of modern and
      historic buildings. Microbial colonization and growth on these stone structures
      is common. Microbial deterioration of stone has been assessed by measuring Ca2+
      released from the stone, using ion selective electrodes and titration with EDTA.
      In this study, the calcium binding fluorochrome Rhod-5N was used to measure Ca2+
      released from limestone by endolithic bacteria as an indicator of
      biodeterioration. In a 17 d flask experiment, Ca2+ released by endolithic
      bacteria was twice that of uninoculated controls. Rhod-5N is a rapid and accurate
      method for measuring microbial biodeterioration of stone.

PMID- 15722152
TI  - Lytic enzyme, labiase for a broad range of Gram-positive bacteria and its
      application to analyze functional DNA/RNA.
AB  - The lytic activity of labiase and achromopeptidase for bacterial DNA/RNA
      extraction were compared. Rapid lysis of many bacterial strains was observed with
      labiase followed by SDS treatment. Both labiase and achromopeptidase showed high
      lytic activity against bacterial strains with the A1alpha chemotype (e.g.,
      Aerococcus viridans) and the A3alpha chemotype (e.g., Staphylococcus epidermidis)
      for cell wall peptidoglycan structures. The lytic activity of labiase was higher
      than that of achromopeptidase against strains with the A1gamma chemotype (e.g.,
      Bacillus subtilis). The activity of labiase was not detrimentally affected with
      increasing NaCl concentration. Labiase lysates were successfully used for rapid
      extraction of DNA and RNA, whereas achromopeptidase lysates degraded RNA. The DNA
      and RNA obtained were successfully used for 16S rRNA amplification and real-time
      RT-PCR detection. It is concluded that labiase is useful for rapid lysis of a
      wide variety of Gram-positive bacteria and can be used for DNA/RNA isolation
      protocols.

PMID- 15722153
TI  - A rapid method to quantify pro-oxidant activity in cultures of wood-decaying
      white-rot fungi.
AB  - A new, rapid method for evaluation of lipid peroxidation promoting (pro-oxidant)
      activity in cultures of wood-decaying fungi was developed. The method is based on
      measurement of the rate of oxygen consumption in the reaction of linoleic acid
      peroxidation initiated by fungal culture filtrates. The liquid cultures of the
      white-rot fungi Bjerkandera adusta and Phanerochaete chrysosporium grown on wheat
      straw-containing glucose-peptone-corn steep liquor medium possessed significant
      levels of the pro-oxidant activity. Other white-rot fungi producing manganese
      peroxidase (MnP) were also found to show the activity. MnP demonstrated a crucial
      role as the major pro-oxidant agent in the fungal cultures. The total pro-oxidant
      activity may be considered as net result of the peroxidation by MnP and the
      inhibition by antioxidant compounds present in the fungal culture fluids.

PMID- 15722154
TI  - Simple method to grow enteric campylobacters in unsupplemented liquid medium
      without the need for microaerophilic kits.
AB  - Campylobacter strains (100 human, animal and environmental isolates) were grown
      in untreated brain heart infusion broth medium (10 ml in tightly capped 20 ml
      capacity universal tubes) without using microaerophilic kits. Cells grown in
      these conditions did not differ in their growth rates, protein profiles or
      substrate utilisation even after 40 passages compared to cells grown under
      microaerophilic conditions. Growth in such conditions provides a cost effective,
      convenient and simple system for growing pure culture of campylobacters and
      obviates the generation of microaerobic conditions using specialised kits.

PMID- 15722155
TI  - Chemiluminometric biochemical induction assay (CBIA) for the detection of DNA
      damaging agents.
AB  - A microbroth chemiluminometric version of the biochemical induction assay (BIA)
      was developed using a chemiluminescent substrate widely used to detect beta
      galactosidase in high-throughput screening (HTS) laboratories. The assay was run
      in both 96-well and 384-well plate formats using the Zymark RapidPlate liquid
      handling system to transfer samples and reagents. Chemiluminescence was read
      using the Victor-2 multilabel counter. The new microbroth chemiluminometric
      method, the CBIA, allowed rapid screening of samples, crude extracts, and pure
      compounds for their DNA-damaging effects in bacteria. In screening a small subset
      of our natural products library samples by the agar plate BIA and the CBIA, the
      latter yielded a higher hit rate, suggesting it is more sensitive than the agar
      plate assay. The CBIA was unaffected by the colored samples often encountered
      during screening of crude natural products extracts.

PMID- 15722156
TI  - A simple PCR-RFLP method for identification and differentiation of 11 Malassezia
      species.
AB  - A PCR-RFLP method targeted toward 26S rDNA and with 2 restriction enzymes, CfoI
      and BstF51, was developed to identify 11 Malassezia species. Not only type and
      standard strains but also 13 clinical isolates were identified successfully in
      this study. The results of identifications were confirmed by DNA sequencing.

PMID- 15722157
TI  - Removal of contaminating DNA from commercial nucleic acid extraction kit
      reagents.
AB  - Due to contamination of DNA extraction reagents, false-positive results can occur
      when applying broad-range real-time PCR based on bacterial 16S rDNA. Filtration
      of the nucleic acid extraction kit reagents with GenElute Maxiprep binding
      columns was effective in removing this reagent-derived contaminating DNA while
      the sensitivity of the assay was maintained.

PMID- 15722159
TI  - Protein transduction: from physiology to technology and vice versa.

PMID- 15722160
TI  - Adaptive translocation: the role of hydrogen bonding and membrane potential in
      the uptake of guanidinium-rich transporters into cells.
AB  - A mechanistic hypothesis is presented for how water-soluble guanidinium-rich
      transporters attached to small cargoes (MW ca. <3000) can migrate across the non
      polar lipid membrane of a cell and enter the cytosol. Positively charged and
      water-soluble, arginine oligomers can associate with negatively charged,
      bidentate hydrogen bond acceptor groups of endogenous membrane constituents,
      leading to the formation of membrane-soluble ion pair complexes. The resultant
      less polar, ion pair complexes partition into the lipid bilayer and migrate in a
      direction, and with a rate, influenced by the membrane potential. The complex
      dissociates on the inner leaf of the membrane and the transporter conjugate
      enters the cytosol. This mechanism could also be involved in the translocation of
      guanidinium-rich molecules that are endocytosed due to their size or the
      conditions of the assay, across the endosomal membrane.

PMID- 15722161
TI  - Nuclear delivery of macromolecules: barriers and carriers.
AB  - Recent evidence for efficient delivery of macromolecules, such as peptides and
      nucleic acids, from the cell exterior to the nucleus offers the interesting
      possibility of developing novel treatments directed at intranuclear targets. The
      findings should also stimulate the search for physiological ligands that utilize
      similar transport mechanisms to regulate pathobiological processes. Cytokines,
      growth factors and their receptors, as well as morphogens have all been shown to
      enter the nucleus to evoke biological responses in target cells. The rational
      design of intracellular drug delivery vehicles requires an increased
      understanding of the elaborate systems that mediate cellular communication and
      coordination with the extracellular environment without inflicting on the
      integrity of the cell. This review discusses some aspects of the carriers and
      barriers in macromolecular transport.

PMID- 15722162
TI  - Cell-penetrating peptides: mechanism and kinetics of cargo delivery.
AB  - Cell-penetrating peptides (CPPs) are short peptides of less than 30 amino acids
      that are able to penetrate cell membranes and translocate different cargoes into
      cells. The only common feature of these peptides appears to be that they are
      amphipathic and net positively charged. The mechanism of cell translocation is
      not known but it is apparently receptor and energy independent although, in
      certain cases, translocation can be partially mediated by endocytosis. Cargoes
      that are successfully internalized by CPPs range from small molecules to proteins
      and supramolecular particles. Most CPPs are inert or have very limited side
      effects. Their penetration into cells is rapid and initially first-order, with
      half-times from 5 to 20 min. The size of smaller cargoes does not affect the rate
      of internalization, but with larger cargoes, the rate is substantially decreased.
      CPPs are novel vehicles for the translocation of cargo into cells, whose
      properties make them potential drug delivery agents, of interest for future use.

PMID- 15722163
TI  - Membrane-permeable arginine-rich peptides and the translocation mechanisms.
AB  - The intracellular delivery of proteins and other bioactive molecules using
      membrane-permeable carrier peptide vectors opens the possibility of establishing
      novel methods of elucidating and controlling cell functions with therapeutic
      potentials. One of the most typical peptide vectors is a short, arginine-rich
      peptide segment derived from the human immunodeficiency virus (HIV)-1 Tat
      protein. We have shown that not only the Tat peptide, but also various arginine
      rich oligopeptides possess very similar characteristics in translocation and
      abilities as a delivery vector. This review summarizes the structures of these
      peptide vectors, especially the Tat and other arginine-rich peptides, and the
      current understanding of their internalization mechanisms.

PMID- 15722164
TI  - Tat peptide-mediated cellular delivery: back to basics.
AB  - Peptides are emerging as attractive drug delivery tools. The HIV Tat-derived
      peptide is a small basic peptide that has been successfully shown to deliver a
      large variety of cargoes, from small particles to proteins, peptides and nucleic
      acids. The 'transduction domain' or region conveying the cell penetrating
      properties appears to be confined to a small (9 amino acids) stretch of basic
      amino acids, with the sequence RKKRRQRRR [S. Ruben, A. Perkins, R. Purcell, K.
      Joung, R. Sia, R. Burghoff, W.A. Haseltine, C.A. Rosen, Structural and functional
      characterization of human immunodeficiency virus tat protein, J. Virol. 63 (1989)
      1-8; S. Fawell, J. Seery, Y. Daikh, C. Moore, L.L. Chen, B. Pepinsky, J. Barsoum,
      Tat-mediated delivery of heterologous proteins into cells, Proc. Natl. Acad. Sci.
      U. S. A. 91 (1994) 664-668; E. Vives, P. Brodin, B. Lebleu, A truncated HIV-1 Tat
      protein basic domain rapidly translocates through the plasma membrane and
      accumulates in the cell nucleus, J. Biol. Chem. 272 (1997) 16010-16017; S.
      Futaki, T. Suzuki, W. Ohashi, T. Yagami, S. Tanaka, K. Ueda, Y. Sugiura, Arginine
      rich peptides. An abundant source of membrane-permeable peptides having potential
      as carriers for intracellular protein delivery, J. Biol. Chem. 276 (2001) 5836
      5840.]. The mechanism by which the Tat peptide adheres to, and crosses, the
      plasma membrane of cells is currently a topic of heated discussion in the
      literature, with varied findings being reported. This review aims to bring
      together some of those findings. Peptide interactions at the cell surface, and
      possible mechanisms of entry, will be discussed together with the effects of
      modifying the basic sequence and attaching a cargo.

PMID- 15722165
TI  - Transmembrane delivery of protein and peptide drugs by TAT-mediated transduction
      in the treatment of cancer.
AB  - The direct intracellular delivery of proteins, or active peptide domains, has,
      until recently, been difficult to achieve due primarily to the bioavailability
      barrier of the plasma membrane, which effectively prevents the uptake of
      macromolecules by limiting their passive entry. Traditional approaches to
      modulate protein function have largely relied on the serendipitous discovery of
      specific drugs and small molecules which could be delivered easily into the cell.
      However, the usefulness of these pharmacological agents is limited by their
      tissue distribution and unlike 'information-rich' macromolecules, they often
      suffer from poor target specificity, unwanted side-effects, and toxicity.
      Likewise, the development of molecular techniques, over the past several decades,
      for gene delivery and expression of proteins has provided for tremendous advances
      in our understanding of cellular processes but has been of surprisingly little
      benefit for the management of genetic disorders. Apart from these gains however,
      the transfer of genetic material into eukaryotic cells either using viral vectors
      or by non-viral mechanisms such as microinjection, electroporation, or chemical
      transfection remains problematic. Moreover, in vivo, gene therapy approaches
      relying on adenoviral vectors are associated with significant difficulties
      relating to a lack of target specificity and toxicity which have contributed to
      poor performance in several clinical trials. Remarkably, the recent
      identification of a particular group of proteins with enhanced ability to cross
      the plasma membrane in a receptor-independent fashion has led to the discovery of
      a class of protein domains with cell membrane penetrating properties. The fusion
      of these protein transduction domain peptide sequences with heterologous proteins
      is sufficient to cause their rapid transduction into a variety of different cells
      in a rapid, concentration-dependent manner. Moreover, this novel technique for
      protein and peptide delivery appears to circumvent many problems associated with
      DNA and drug based methods. This technique may represent the next paradigm in our
      ability to modulate cell function and offers a unique avenue for the treatment of
      disease.

PMID- 15722166
TI  - Transcellular protein transduction using the Tat protein of HIV-1.
AB  - The Tat protein of HIV-1 is a powerful transactivator of gene expression. By
      interacting with a structured RNA sequence at the 5' end of the viral mRNA, it
      promotes the remodeling of chromatin and the recruitment of processive RNA
      polymerase complexes at the viral promoter. In addition to these transcriptional
      functions, a short amino acid motif, highly enriched in basic amino acids,
      promotes the export of the protein from the expressing cells. Once in the
      extracellular environment, the same basic domain of Tat binds to cell surface
      heparan sulfate proteoglycans; through this interaction, the protein is
      internalized by a variety of different cell types. Cellular internalization of
      Tat and Tat fusion proteins requires the integrity of cell membrane lipid rafts
      and mainly occurs through caveolar endocytosis. The Tat basic domain, when
      attached to large protein cargos, also mediates their efficient cellular
      internalization and can be thus utilized for transcellular protein transduction.
      This property has already been successfully exploited for the delivery of
      heterologous proteins, nanoparticles, liposomes, phage and viral vectors, and
      plasmid DNA. The biological significance of intercellular Tat trafficking in the
      context of viral infection still remains elusive.

PMID- 15722167
TI  - Intracellular targeting of polymer-bound drugs for cancer chemotherapy.
AB  - Macromolecules have been traditionally employed as drug carriers due to their
      ability to selectively accumulate in malignant tissues compared to healthy
      tissues by either passive or active targeting, thus precluding undesirable side
      effects generated by free drug. The therapeutic activity proffered by such
      conjugates requires that the drug concentrate at its specific subcellular target
      such as the nucleus. Thus, the suitability of macromolecules as carriers also
      extends to their propensity to deliver the drug to a predetermined intracellular
      location. As binding a macromolecule to a drug facilitates cellular uptake by
      endocytosis, various approaches have been employed to either guide the drug to
      targets different from endosomal/lysosomal compartments by mediating vesicular
      escape, or to directly accomplish intracellular (cytoplasmic and nuclear)
      localization. This review discusses the utility of macromolecules in drug
      delivery and describes the numerous modalities (with a focus on cell-penetrating
      peptides) currently available for achieving effective intracellular drug
      delivery.

PMID- 15722168
TI  - Intracellular delivery of large molecules and small particles by cell-penetrating
      proteins and peptides.
AB  - Cell-penetrating peptides (CPPs) have been used to overcome the lipophilic
      barrier of the cellular membranes and deliver large molecules and even small
      particles inside the cell for their biological actions. CPPs are being used to
      deliver inside cell a large variety of cargoes such as proteins, DNA, antibodies,
      contrast (imaging) agents, toxins, and nanoparticular drug carriers including
      liposomes. In this paper, we have reviewed the delivery of different molecules
      and particles mediated by TAT, Antp, VP22, and other CPPs as well as potential
      applications of these delivery systems in different areas of vaccine development,
      cancer immunotherapy, gene delivery, and cellular imaging.

PMID- 15722170
TI  - Sorption of europium on a goethite surface: influence of background electrolyte.
AB  - An experimental and theoretical study of Eu(III) sorption on goethite surface was
      performed in the presence of different background electrolytes (NaCl, NaNO3,
      KNO3). Results were described using a simple surface complexation, the double
      layer model (DLM), and calculations were performed using either Fiteql3.2 or
      Jchess codes. The surface acidity constants and sites density were first
      determined by potentiometric titrations. The influence of electrolyte ions on the
      value of point of zero charge was studied by both potentiometric and
      electrokinetic measurements in order to assess their possible retention on
      goethite. The sorption of Eu(III) was then investigated by the batch method, in
      the three background electrolytes, as a function of pH. The presence of
      electrolyte ions was found to decrease the immobilization of Eu on goethite.
      Sorption results were modelled considering ternary surface complexes (goethite
      surface/europium/electrolyte ions).

PMID- 15722169
TI  - The role of alpha-helical structure in p53 peptides as a determinant for their
      mechanism of cell death: necrosis versus apoptosis.
AB  - Peptides derived from the N-terminal and C-terminal regions of the p53 tumor
      suppressor protein, linked to the membrane transduction domain of Antennapedia,
      have both been found to have significant cytotoxic effects selectively in human
      cancer cells. However, the N-terminal and C-terminal p53 peptides apparently
      display very different mechanisms for their anticancer effects. These
      differential effects can be attributed to dissimilar abilities to form
      distinctive 3-dimensional structures in extracellular-matrix-like aqueous
      solution that enable unique and selective cancer cell membrane penetration and
      effect. N-terminally based p53 peptides, with their ability to form distinctive S
      shaped helix-loop-helix structures, are able to rapidly disrupt cancer cell
      membranes via toroidal-like pore formation causing necrosis; conversely, C
      terminally based p53 peptides, due to their more random coil configuration, can
      be transduced across cancer cell membranes and bind to its intracellular target
      to cause a Fas pathway mechanism of apoptosis.

PMID- 15722171
TI  - Formation and stability of polychlorinated biphenyl Pickering emulsions.
AB  - An emulsion stabilized by colloidal suspensions of finely divided solids is known
      as a Pickering emulsion. The potential for polychlorinated biphenyls (PCBs) to
      form Pickering emulsions ex situ when in contact with powdered solids, such as
      clays and metal oxides, is investigated here. Bentonite, iron oxide and magnesium
      oxide dispersions proved to be robust Pickering emulsion stabilizers, whereas
      manganese oxide dispersions were not. Batch experiments revealed that emulsions
      can be formed using a moderately low energy input and can be stabilized with
      solid concentrations as low as 0.5 wt.%. For the base conditions (volumetric oil
      fraction (phi(oil))=30 vol.%; solid concentration (chi)=2 wt.%), the formed
      emulsions were indefinitely stable and the initial average droplet diameters
      varied from 80 to 258 mum, depending on the solid used in the colloidal
      dispersion. The average droplet size varied at early time, but for most
      conditions stabilized to a steady-state value 1 week after preparation. The
      effect of Ostwald ripening was limited. At greater than 0.5 wt.% concentration,
      the efficiency of the solid dispersion as a stabilizer was dependant on the
      volumetric oil fraction but not on the solid concentration. Generally, systems
      with volumetric oil fractions outside of the 20-70 vol.% range were unstable. The
      emulsions' droplet stability, average droplet size and size distribution were
      observed to vary as a function of the amount of energy provided to the system,
      the volumetric oil fraction, and the concentration of the solid in the aqueous
      dispersion. It is hypothesized that drilling through fractured rock in the
      immediate vicinity of dense, non-aqueous phase liquid (DNAPL) PCBs may provide
      both the energy and solid material necessary to form Pickering emulsions.

PMID- 15722172
TI  - Cost-effective sampling network design for contaminant plume monitoring under
      general hydrogeological conditions.
AB  - A new simulation-optimization methodology is developed for cost-effective
      sampling network design associated with long-term monitoring of large-scale
      contaminant plumes. The new methodology is similar in concept to the one
      presented by Reed et al. (Reed, P.M., Minsker, B.S., Valocchi, A.J., 2000a. Cost
      effective long-term groundwater monitoring design using a genetic algorithm and
      global mass interpolation. Water Resour. Res. 36 (12), 3731-3741) in that an
      optimization model based on a genetic algorithm is coupled with a flow and
      transport simulator and a global mass estimator to search for optimal sampling
      strategies. However, this study introduces the first and second moments of a
      three-dimensional contaminant plume as new constraints in the optimization
      formulation, and demonstrates the proposed methodology through a real-world
      application. The new moment constraints significantly increase the accuracy of
      the plume interpolated from the sampled data relative to the plume simulated by
      the transport model. The plume interpolation approaches employed in this study
      are ordinary kriging (OK) and inverse distance weighting (IDW). The proposed
      methodology is applied to the monitoring of plume evolution during a pump-and
      treat operation at a large field site. It is shown that potential cost savings up
      to 65.6% may be achieved without any significant loss of accuracy in mass and
      moment estimations. The IDW-based interpolation method is computationally more
      efficient than the OK-based method and results in more potential cost savings.
      However, the OK-based method leads to more accurate mass and moment estimations.
      A comparison of the sampling designs obtained with and without the moment
      constraints points to their importance in ensuring a robust long-term monitoring
      design that is both cost-effective and accurate in mass and moment estimations.
      Additional analysis demonstrates the sensitivity of the optimal sampling design
      to the various coefficients included in the objective function of the
      optimization model.

PMID- 15722173
TI  - A pore-scale investigation of a multiphase porous media system.
AB  - Pore-scale processes govern fundamental behavior in multiphase porous media
      systems. A high-resolution, three-dimensional image of the interior of a
      multiphase porous media system was obtained using synchrotron X-ray tomography.
      The system was imaged at a resolution of 12.46 mum following entrapment of the
      nonwetting phase at residual saturation. First, the physically representative
      network structure of the porous media system is extracted from the void space.
      This provides a direct mapping of the pore bodies and throats and enables pore
      level calculations of coordination numbers, aspect ratios, and pore body and
      throat correlations. Next, algorithms developed to calculate properties of the
      entrapped nonwetting phase, such as volume, sphericity, interfacial area, and
      orientation, are applied to the residual nonwetting phase blobs. Finally,
      correlations between the pore network structure and nonwetting phase
      characteristics are examined. As expected, it was found that the nonwetting phase
      was trapped primarily in the largest pore spaces, the pore bodies with the
      highest aspect ratios, and the pore bodies with the highest coordination numbers.
      This work shows that, while there may be limitations related to the ability to
      capture REV-sized domains for some of the multiphase flow properties and
      phenomena, high-resolution X-ray tomography is able to provide the high quality
      datasets needed to observe and quantify the pore-scale phenomena and processes
      that govern multiphase flow in unconsolidated porous media systems.

PMID- 15722174
TI  - Modeling field-scale multiple tracer injection at a low-level waste disposal site
      in fractured rocks: effect of multiscale heterogeneity and source term
      uncertainty on conceptual understanding of mass transfer processes.
AB  - Multiple factors may affect the scale-up of laboratory multi-tracer injection
      into structured porous media to the field. Under transient flow conditions and
      with multiscale heterogeneities in the field, previous attempts to scale-up
      laboratory experiments have not answered definitely the questions about the
      governing mechanisms and the spatial extent of the influence of small-scale mass
      transfer processes such as matrix diffusion. The objective of this research is to
      investigate the effects of multiscale heterogeneity, mechanistic and site model
      conceptualization, and source term density effect on elucidating and interpreting
      tracer movement in the field. Tracer release and monitoring information
      previously obtained in a field campaign of multiple, conservative tracer
      injection under natural hydraulic gradients at a low-level waste disposal site in
      eastern Tennessee, United States, is used for the research. A suite of two-pore
      domain, or fracture-matrix, groundwater flow and transport models are calibrated
      and used to conduct model parameter and prediction uncertainty analyses. These
      efforts are facilitated by a novel nested Latin-hypercube sampling technique. Our
      results verify, at field scale, a multiple-pore-domain, multiscale mechanistic
      conceptual model that was used previously to interpret only laboratory
      observations. The results also suggest that, integrated over the entire field
      site, mass flux rates attributable to small-scale mass transfer are comparable to
      that of field-scale solute transport. The uncertainty analyses show that fracture
      spacing is the most important model parameter and model prediction uncertainty is
      relatively higher at the interface between the preferred flow path and its parent
      bedrock. The comparisons of site conceptual models indicate that the effect of
      matrix diffusion may be confined to the immediate neighborhood of the
      preferential flow path. Finally, because the relatively large amount of tracer
      needed for field studies, it is likely that source term density effect may
      exaggerate or obscure the effect of matrix diffusion on the movement of tracers
      from the preferred flow path into the bedrock.

PMID- 15722175
TI  - Fate of disinfection by-products in groundwater during aquifer storage and
      recovery with reclaimed water.
AB  - Knowledge on the behaviour of disinfection by-products (DBPs) during aquifer
      storage and recovery (ASR) is limited even though this can be an important
      consideration where recovered waters are used for potable purposes. A reclaimed
      water ASR trial in an anoxic aquifer in South Australia has provided some of the
      first quantitative information at field-scale on the fate and transport of
      trihalomethanes (THMs) and haloacetic acids (HAAs). The results revealed that THM
      half-lives varied from <1 to 65 days, with persistence of chloroform being
      highest and bromoform lowest. HAA attenuation was rapid (<1 day). Rates of THM
      attenuation were shown to be highly dependent on the geochemical environment as
      evidenced by the 2-5 fold reduction in half-lives at the ASR well which became
      methanogenic during the storage phase of the trial, as compared to an observation
      well situated 4 m away, which remained nitrate-reducing. These findings agree
      with previous laboratory-based studies which also show persistence declining with
      increased bromination of THMs and reducing redox conditions. Modelling suggests
      that the chlorinated injectant has sufficient residual chlorine and natural
      organic matter for substantial increases in THMs to occur within the aquifer,
      however this is masked in some of the field observations due to concurrent
      attenuation, particularly for the more rapidly attenuated brominated compounds.
      The model is based on data taken from water distribution systems and may not be
      representative for ASR since bromide and ammonia concentrations in the injected
      water and the possible role of organic carbon in the aquifer were not taken into
      consideration. During the storage phase DBP formation potentials were reduced as
      a result of the removal of precursor material despite an increase in the THM
      formation potential per unit weight of total organic carbon. This suggests that
      water quality improvements with respect to THMs and HAAs can be achieved through
      ASR in anoxic aquifers.

PMID- 15722176
TI  - Acquisition of visuomanual skills and improvement of information processing
      capacities in 6- to 10-year-old children performing a 2D pointing task.
AB  - The aim of this study was to investigate motor performance and visuomanual
      control through the analysis of Fitts' law in 6-, 8-, and 10-year-old children
      and adults performing a constrained two-dimensional pointing task. Participants
      were required to point and click on targets appearing on a laptop computer screen
      with a standard computer mouse. Three sizes of targets were used to create
      different indexes of difficulty. Analysis first showed linear visuomanual
      abilities to perform bi-dimensional pointing movements. It appears that
      developmental motor performance changes are due to combined enhanced programming
      processes and online feedback processing. Immature visuomanual control of 10-year
      old children could be explained by higher cognitive requirements related to the
      task. As predicted by Fitts' law, movement time linearly decreases with the
      enlargement of target width. Moreover, a regression analysis of movement time on
      index of difficulty (ID) clearly showed significant differences for cognitive
      processing capacities with age: increasing ID effects are more dramatic in
      younger children performing computer mouse pointing movements.

PMID- 15722177
TI  - Detection of 111In-oxine-labeled bone marrow stromal cells after intravenous or
      intralesional administration in chronic paraplegic rats.
AB  - Recent studies suggested that bone marrow stromal cells (BMSC) may have a
      therapeutic role in the treatment of paraplegia secondary to severe spinal cord
      injury (SCI). For this reason, we have studied the possibility of using nuclear
      medicine imaging techniques to evaluate the permanency and migration of BMSC
      after transplantation procedures in chronic paraplegic Wistar rats. After
      intravenous administration of 111In-oxine-labeled BMSC, gammagraphic images
      showed that the activity distributed all over the organism, but in the spinal
      cord only scarce activity was identified. When 111In-oxine-labeled BMSC were
      injected within the traumatic centromedullary cavity of paraplegic animals, the
      gammagraphic images showed persistent activity in the lesion zone, without any
      activity migrating to the rest of the organism, at least during the whole time of
      the study (10 days after transplantation procedures). Our results show the
      utility of 111In labeling for to know the permanency and distribution of BMSC
      after grafting procedures, and suggest the convenience of the intralesional
      administration of BMSC, instead of the intravenous administration, in the
      treatment of chronic traumatic paraplegia.

PMID- 15722178
TI  - BDNF, but not NT-4, is necessary for normal development of Meissner corpuscles.
AB  - Meissner corpuscles are rapidly adapting cutaneous mechanoreceptors depending for
      development on TrkB expressing sensory neurons, but it remains to be established
      which of the known TrkB ligands, BDNF or NT-4, is responsible of this dependence.
      In this study we analyze Meissner corpuscles in the digital pads of mice with
      target mutations in the genes encoding for either BDNF or NT-4, using
      immunohistochemistry and transmission-electron microscopy, and they were
      identified based on their morphology and expression of S100 protein. All wild
      type animals as well as NT-4(-/-) animals and BDNF and NT4 heterozygous animals
      have Meissner corpuscles that are normal in number and size. However, Meissner
      corpuscles are absent the BDNF(-/-) mice. These results suggest that BDNF is the
      only TrkB ligand involved in the development of Meissner corpuscles in murine
      glabrous skin, and it probably regulates the development of the sensory neurons
      that innervate Meissner corpuscles.

PMID- 15722179
TI  - Localization of NADPH oxidase subunits in neonatal sympathetic neurons.
AB  - Reactive oxygen species (ROS) trigger programmed cell death in neonatal
      sympathetic neurons that have been deprived of nerve growth factor (NGF),
      however, the source of these oxygen intermediates has not been established. Using
      laser scanning confocal microscopy (LSCM), the intracellular distribution of the
      subunits of the ROS-generating enzyme NADPH oxidase was examined in sympathetic
      neurons of the superior cervical ganglion (SCG). Optical sectioning using LSCM
      showed that gp91-phox and p22-phox co-localize in neurons at the cell membrane,
      while the p47-phox and p67-phox subunits are found uniformly distributed in the
      cytoplasm of neurons maintained in the presence of NGF. Within 4h after NGF
      deprivation, both the p47-phox and p67-phox subunits exhibit punctate staining in
      the cytoplasm and at the membrane. Furthermore, a sub-population of the cytosolic
      p47-phox appeared to co-localize with the membrane-bound gp91-phox in NGF
      deprived neurons. These data provide support for the presence of NADPH oxidase in
      sympathetic neurons and suggest that this enzyme may become activated following
      the withdrawal of NGF.

PMID- 15722180
TI  - Developmental changes in hyperexcitability of CA1 pyramidal neurons induced by
      repeated brief episodes of hypoxia in the rat hippocampal slices.
AB  - We have previously demonstrated that repeated exposure of adult rat hippocampal
      slices to brief episodes of hypoxia induce a sustained decrease in the threshold
      of stimulus-evoked population spike discharges in CA1 pyramidal neurons [O.
      Godukhin, A. Savin, S. Kalemenev, S. Levin, Neuronal hyperexcitability induced by
      repeated brief episodes of hypoxia in rat hippocampal slices: involvement of
      ionotropic glutamate receptors and L-type Ca2+ channels, Neuropharmacology 42
      (2002) 459-466, S.V. Kalemenev, A.V. Savin, S.G. Levin, O.V. Godukhin, Long-term
      potentiation and epileptiform activity induced by brief hypoxic episodes in CA1
      area of the rat hippocampal slices. Russ. Physiol. J. 86 (2000) 1676-1681]. In
      the present study, using the above-mentioned in vitro model of epileptogenesis,
      we compared the developmental changes in hypoxia-induced hyperexcitability of CA1
      neuronal network in the rat hippocampal slices prepared from three age rat
      groups: postnatal days (P) 13-14 (young), P60-70 (adult) and P600-650 (old).
      Furthermore, we were interested in learning about an age dependence of the
      hypoxia-induced changes in the efficacies of glutamatergic transmission and
      paired-pulse inhibition in CA3-CA1 synapses that may underlie ontogenetic
      differences in seizure susceptibility in hippocampal network. The principal
      results of this work are summarized as follow. In comparison with P60-70
      hippocampal slices, CA1 pyramidal neurons in P13-14 and P600-650 slices showed
      intrinsically (without repeated brief hypoxa) an increased propensity to generate
      epileptiform stimulus-evoked population spike discharges. However, in contrast to
      adult and old animals, repeated brief episodes of hypoxia are incapable to induce
      a sustained decrease in the threshold of stimulus-evoked population spike
      discharges in CA1 pyramidal neurons of hippocampal slices prepared from of P13-14
      rats, though they transform paired-pulse inhibition to paired-pulse facilitation
      and induce hypoxic LTP in CA3-CA1 synapses. The role of some other factors in the
      developmental changes in hyperexcitability of CA1 pyramidal neurons in response
      to repeated brief episodes of hypoxia is discussed.

PMID- 15722181
TI  - Remote effects of voluntary teeth clenching on excitability changes of the human
      hand motor area.
AB  - The aim of the present study was to investigate effects of voluntary teeth
      clenching (VTC) on motor evoked potentials (MEPs) from the first dorsal
      interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) by different
      oriented currents (anterior-medially (AM), posterior-laterally (PL)) of the human
      motor cortex. In active FDI, VTC enhanced MEP responses induced by AM directed
      current but reduced these responses induced by PL. In relaxed FDI, VTC enhanced
      MEP responses by AM but had no significant effects on those by PL. Thus, the
      results suggest that any components produced by AM directed current were
      enhanced, whereas those by PL directed currents were not affected or reduced. The
      present evidence indicates that I-waves recorded at the same latency were not
      completely the same between those produced by AM and PL directed currents.
      Because VTC had no influence on responses to brainstem electrical stimulation
      (BES) or F-waves just after the onset of teeth clenching [T. Furubayashi, K.
      Sugawara, T. Kasai, A. Hayashi, R. Hanajima, Y. Shiio, N.K. Iwara, Y. Ugawa,
      Remote effects of self-paced teeth clenching on the excitability of hand motor
      area, Exp. Brain Res., 148 (2003) 261-265], these modulatory effects on MEPs to
      both AM and PL directed currents must be due to changes of the motor cortical
      excitability. Thus, we conclude that VTC affects the motor cortical circuits
      activated by PL and AM directed currents differentially; it facilitates the one
      and inhibits the other. This is the first demonstration of opposite effects of
      the same maneuver on MEP responses elicited by AM and PL directed currents.

PMID- 15722182
TI  - Cloning and expression of the human NMDA receptor subunit NR3B in the adult human
      hippocampus.
AB  - The mammalian genome encodes seven different NMDA receptor subunits. All of these
      subunits have been cloned in the human except for NR3B. Here, we have
      successfully obtained two full-length clones of human NR3B using a PCR-based
      cloning approach. The open reading frame of the consensus sequence contains 3129
      nucleotides translating into 1043 amino acids. The overall polypeptide sequence
      identity with mouse NR3B is 74.9%, which is lower than for the other six NMDA
      receptor subunits. In particular, the translated part of exon 9 is only 37.8%
      identical between human and mouse. The GRIN3B gene, which encodes human NR3B,
      maps to chromosome 19p13.3, between WDR18 and C19orf6 (membralin). Human NR3B is
      encoded by nine exons, as in mouse NR3B, and exon-intron boundaries are conserved
      between the species. However, exon 9 is substantially longer in the human. In
      situ hybridization data shows that NR3B mRNA is expressed in the human
      hippocampal formation (CA1-CA4 and dentate gyrus) and adjacent neocortex. The
      expression of NR3A mRNA was restricted to the dentate gyrus and layers IV and V
      of the neocortex. Our results may have implications for the understanding of the
      role of NMDA receptors for physiological and pathological processes in these
      forebrain regions.

PMID- 15722183
TI  - ACE I/D polymorphism is a risk factor of Alzheimer's disease but not of vascular
      dementia.
AB  - Different studies have investigated the effect of the angiotensin converting
      enzyme (ACE) insertion/deletion (I/D) polymorphism on the risk of Alzheimer
      dementia (AD). However, results on the association of the ACE-I allele with AD
      have been inconclusive. A recent meta-analysis reported an association of the I
      allele with the risk of AD. A few small studies also investigated the effect of
      ACE polymorphism on the risk of vascular dementia (VD). We have investigated the
      effect of ACE I/D polymorphism in 351 AD and 155 VD patients and 348 healthy
      controls. We found the I/I genotype to be associated with an increased risk of
      AD, but not with the risk of VD. Cell-specific effects of ACE polymorphism are
      suggested, additional studies on neuronal cells might help to understand the role
      of this polymorphism in AD.

PMID- 15722184
TI  - Norepinephrine transporter (NET) promoter and 5'-UTR polymorphisms: association
      analysis in panic disorder.
AB  - Several biochemical and pharmacological studies suggest that the
      catecholaminergic system involving the norepinephrine transporter (NET) is
      relevant for the pathogenesis of panic disorder. Three single nucleotide
      polymorphisms in the promoter or untranslated 5' region of the NET gene were
      investigated by means of RFLP analysis in a sample of 115 German patients with
      panic disorder and 115 matched controls. Statistical analysis failed to show
      association with the overall diagnosis of panic disorder. In the subgroup of
      patients with panic disorder without agoraphobia, however, two polymorphisms were
      found to be associated with the disease (G/C (rs2397771): p < 0.05; T/C
      (rs2242446): p < 0.01). While our data do not support a major function of the NET
      gene in the development of panic disorder, it may play a role in the subgroup of
      panic disorder without agoraphobia.

PMID- 15722186
TI  - Investigation of transcription factor AP-2 beta genotype in women with
      premenstrual dysphoric disorder.
AB  - It has repeatedly been shown that the serotonergic system is involved in the
      symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are
      reported to differ from symptom-free controls with regard to serotonin-related
      biological markers. Evidence from family and twin studies suggests a genetic
      contribution to the aetiology of PMDD. The expression of human transcription
      factor AP-2beta in neural crest cell lineages and neuroectodermal cells suggests
      that this protein may be of importance for functional characteristics of neurons
      by regulating the expression of target genes. Within the monoaminergic systems,
      several genes have binding sites for AP-2beta in regulatory regions, suggesting
      an involvement of AP-2beta in these systems. The gene encoding AP-2beta is
      located on chromosome 6p12-p21.1 and includes a polymorphic region consisting of
      a variable number of [CAAA] repeats located in the second intron. We have earlier
      shown that AP-2beta genotype is associated with serotonergic phenotypes and that
      brainstem levels of AP-2beta correlate positively to serotonin metabolism in rat
      frontal cortex. The aim of this study was to investigate the relationship between
      PMDD and transcription factor AP-2beta genotype. The participants included 176
      women with PMDD and 91 healthy controls. Genotyping was performed by polymerase
      chain reactions. We did not observe any differences in AP-2beta genotype
      frequencies between PMDD subjects and controls. Our results suggest that AP-2beta
      genotype is not a risk factor for PMDD. To our knowledge, this is the first study
      investigating transcription factor AP-2beta genotype in women with PMDD. Hence,
      these results should be considered preliminary until replicated.

PMID- 15722185
TI  - Ethanol withdrawal reduces cerebellar parvalbumin expression in a manner reversed
      by estrogens.
AB  - Parvalbumin (PA) is a calcium-binding protein that has been implicated in
      neuroprotection. We examined whether the stimulus effect of ethanol withdrawal
      (EW) alters the expression of PA in a manner that is prevented by 17beta
      estradiol (E2). Ovariectomized rats implanted with E2 (EW/E2) or oil (EW/Oil)
      pellets received chronic ethanol (7.5%, w/v, 5 weeks) or control dextrin diets
      (Dex/Oil). At 24h of EW, rats were tested for overt EW signs, and the cerebellum
      was prepared for immunoblotting and immunohistological assessment for PA. The
      EW/Oil group showed a higher EW sign score, a lower PA expression, and fewer PA
      positive Purkinje neurons than the dextrin control group. In the EW/E2 group, EW
      sign scores, PA expression, and PA-positive Purkinje neurons were not
      significantly different from those in the control dextrin group. These data
      suggest that E2 treatment protects against the PA-suppression associated with EW
      toxicity.

PMID- 15722187
TI  - Effects of a fast cable car ascent to an altitude of 2700 meters on EEG and ECG.
AB  - In the Eastern Alps, the Dachstein massif with a height of almost 3000 m is an
      ideal location for investigating the effects of changes in altitude on the human
      body. Within a few minutes, a cable car facilitates an ascent from 1702 to 2700 m
      above sea level, where the partial pressure of oxygen is about 550 mmHg (as
      compared to 760 mmHg at sea level). In this study, 10 healthy subjects performed
      a reaction time task at 990 m and 2700 m in altitude. The subjects were
      instructed to perform a right hand index finger movement as fast as possible
      after a green light flashed (repeated 50 times). The corresponding
      electrocardiogram (ECG) and the electroencephalogram (EEG) were recorded. From
      the ECG heart rate and heart rate variability measures in the time and frequency
      domain were calculated. An event-related desynchronization/synchronization
      (ERD/ERS) analysis was performed with the EEG data. Finally, the EEG activity and
      the ECG parameters were correlated. The study showed that with the fast ascent to
      2700 m the heart rate increased and the heart rate variability measures
      decreased. The correlation analysis indicated a close relationship between the
      EEG activity and the heart rate and heart rate variability. Furthermore it was
      shown for the first time that the beta ERS in the 14-18 Hz frequency range (post
      movement beta ERS) was significantly reduced at high altitude. Very interesting
      also is the loss of correlation between EEG activity and cardiovascular measures
      during finger movement at high altitude. The suppressed post-movement beta ERS at
      the altitude of 2700 m may be interpreted as results of an increased cortical
      excitability level when compared with the reference altitude at 990 m above sea
      level.

PMID- 15722188
TI  - Intramodal perceptual grouping modulates multisensory integration: evidence from
      the crossmodal dynamic capture task.
AB  - We investigated the extent to which intramodal visual perceptual grouping
      influences the multisensory integration (or grouping) of auditory and visual
      motion information. Participants discriminated the direction of motion of two
      sequentially presented sounds (moving leftward or rightward), while
      simultaneously trying to ignore a task-irrelevant visual apparent motion stream.
      The principles of perceptual grouping were used to vary the direction and extent
      of apparent motion within the irrelevant modality (vision). The results
      demonstrate that the multisensory integration of motion information can be
      modulated by the perceptual grouping taking place unimodally within vision,
      suggesting that unimodal perceptual grouping processes precede multisensory
      integration. The present study therefore illustrates how intramodal and
      crossmodal perceptual grouping processes interact to determine how the
      information in complex multisensory environments is parsed.

PMID- 15722189
TI  - Differential circadian expression of endothelin-1 mRNA in the rat suprachiasmatic
      nucleus and peripheral tissues.
AB  - The vasoconstrictor endothelin-1 (ET-1) is implicated in normal neuronal
      functions. Here we show the circadian expression of ET-1 mRNA in the rat
      suprachiasmatic nucleus (SCN) that is considered to be the location of the
      central circadian pacemaker, as well as in peripheral tissues including the
      brain, heart, and lungs. The expression of ET-1 in the SCN oscillated with a peak
      at Zeitgeber time (ZT) 4 under light-dark conditions. A significant number of
      cells in the SCN was stained with ET-1 probe during circadian time (CT) 6, but
      there was no significant staining at CT18 by mRNA in situ hybridization. The
      circadian rhythm of ET-1 mRNA in the whole brain also oscillated, but peaked at
      ZT20. Endothelin-1 expression in the lungs and heart peaked at ZT12 and ZT20,
      respectively. The results are the first description of the circadian expression
      of ET-1 mRNA. The diversity of rhythmic expressions among the SCN, whole brain,
      lungs and heart suggests that ET-1 has different functions in these tissues.

PMID- 15722190
TI  - Negative symptoms of schizophrenia could explain discrepant data on the
      association between the 5-HT2A receptor gene and response to antipsychotics.
AB  - Pharmacogenetic studies assessing the role of 5-HT(2A) receptor gene in
      antipsychotic efficacy yielded conflicting data. Phenotypical heterogeneity of
      schizophrenia might explain such discrepancies. For example, negative symptoms
      are known to reflect severity of illness and to restrain therapeutic response. On
      this basis, we re-assessed the possible influence of the -1438A/G polymorphism of
      the 5-HT(2A) receptor gene on the clinical efficacy of atypical antipsychotics
      with focus on several relevant dimensions. One hundred and sixteen French
      schizophrenic subjects treated for at least 1 month by atypical antipsychotics
      were screened for treatment response according to the May and Dencker scale.
      Gender, age at onset, duration and severity of illness, intensity of negative and
      positive symptoms at discharge were investigated. The intensity of negative
      symptoms at discharge was the only variable explaining May and Dencker score (p <
      0.001), and was significantly associated with the AA genotype of the -1438A/G
      polymorphism of the 5-HT(2A) receptor gene (p = 0.03). However, the A allele was
      not independently associated with refractoriness to atypical antipsychotics.
      Accordingly, the score reached in the Scale for the Assessment of Negative
      Symptoms (SANS) appeared as a confounding factor between therapeutic response and
      the -1438A/G polymorphism of the 5-HT(2A) receptor gene, at least in our sample.
      This data indicate that negative symptoms are worth being systematically assessed
      in pharmacogenetic studies aimed at analysing candidate genes in schizophrenia.

PMID- 15722191
TI  - Regulatory mechanisms and their therapeutic implications of interleukin-12
      production in immune cells.
AB  - Studies with neutralizing anti-interleukin (IL)-12 antibodies and IL-12-deficient
      mice have suggested that endogenous IL-12 plays an important role in the normal
      host defense against infection by a variety of intracellular microorganisms.
      However, IL-12 also appears to play a central role in the pathogenesis of
      autoimmune diseases such as multiple sclerosis or rheumatic arthritis. Therefore,
      it is crucial to understand how IL-12 is produced and its production is regulated
      at the molecular level. IL-12 production is differentially regulated through
      multiple pathways, which can be classified as follows: nuclear factor-kappaB (NF
      kappaB) and other transcription factors, p38 mitogen-activated protein (MAP)
      kinase, cyclic adenosine monophosphate (cyclic AMP)-modulating molecules, cell
      membrane ion channels and pumps, nitric oxide (NO), and receptors. In this review
      we describe the regulatory mechanisms of IL-12 production in immune cells and
      also some agents to control IL-12 production for the treatment of immune-related
      diseases.

PMID- 15722192
TI  - The casein kinase 1 family: participation in multiple cellular processes in
      eukaryotes.
AB  - Phosphorylation of serine, threonine and tyrosine residues by cellular protein
      kinases plays an important role in the regulation of various cellular processes.
      The serine/threonine specific casein kinase 1 and 2 protein kinase families--(CK1
      and CK2)--were among the first protein kinases that had been described. In recent
      years our knowledge of the regulation and function of mammalian CK1 kinase family
      members has rapidly increased. Extracellular stimuli, the subcellular
      localization of CK1 isoforms, their interaction with various cellular structures
      and proteins, as well as autophosphorylation and proteolytic cleavage of their C
      terminal regulatory domains influence CK1 kinase activity. Mammalian CK1 isoforms
      phosphorylate many different substrates among them key regulatory proteins
      involved in the control of cell differentiation, proliferation, chromosome
      segregation and circadian rhythms. Deregulation and/or the incidence of mutations
      in the coding sequence of CK1 isoforms have been linked to neurodegenerative
      diseases and cancer. This review will summarize our current knowledge about the
      function and regulation of mammalian CK1 isoforms.

PMID- 15722193
TI  - Tyrosine phosphorylation of phospholipase D1 by v-Src does not per se result in
      activation.
AB  - The relationship between tyrosine phosphorylation and activation of phospholipase
      D1 (PLD1) by v-Src was examined. Co-expression of v-Src and PLD1 in COS-7 cells
      resulted in increased activity and marked tyrosine phosphorylation of PLD1. PLD
      activity was increased in membranes or immunoprecipitates prepared from these
      cells. Dephosphorylation of the immunoprecipitated enzyme by tyrosine phosphatase
      or phosphorylation by c-Src produced no changes in its activity. Tyrosine
      phosphorylation induced by v-Src caused a shift of the enzyme from the Triton
      soluble to the Triton-insoluble fraction. v-Src and PLD1 could be co
      immunoprecipitated from cells co-expressing these and were co-localized in the
      perinuclear region as assessed by immunofluorescence. Mutation of the
      palmitoylation sites of PLD1 significantly reduced tyrosine phosphorylation by v
      Src. It is concluded that tyrosine phosphorylation of PLD1 by v-Src does not per
      se alter its activity. It is proposed that activation of PLD1 by v-Src in vivo
      may involve association/colocalization of the two proteins.

PMID- 15722194
TI  - Suppression of MEK/ERK signalling by Myc: role of Bin-1.
AB  - We report for the first time that over-expression of Myc suppresses mitogen
      activated ERK kinase (MEK)/extracellular regulated kinase (ERK) signalling in
      chick embryo fibroblasts (CEF). Myc does not interfere with individual components
      of the signalling cascade, since efficient signal propagation via MEK and ERK in
      Myc-infected CEF can be seen. However, using the Myc-binding domain (MBD) of Bin
      1, which binds to and negatively regulates the activity of Myc, we selectively
      suppressed Myc-induced apoptosis, without affecting its transforming properties.
      This was accompanied by a restoration in MEK/ERK signalling, suggesting a
      critical role for this pathway in regulating apoptosis in these cells. This was
      also confirmed using a specific pharmacological inhibitor of MEK. Experiments
      with conditioned media suggest that over-expression of Myc may inhibit autocrine
      growth factor production, which can be restored by co-expression of MBD. Although
      the identity of the growth factor(s) is not known, we propose a feedback
      mechanism whereby Myc interferes with growth factor signalling.

PMID- 15722195
TI  - Disruption of two putative nuclear localization sequences is required for
      cytosolic localization of mitogen-activated protein kinase phosphatase-2.
AB  - MAP kinase phosphatase-2 (MKP-2) is a member of a family of dual specificity
      phosphatases (DSPs) that function in both the cytosol and nucleus to inactivate
      the MAP kinases. The mechanism that controls the subcellular distribution of
      these proteins is currently unclear. In this study, we have used site-directed
      mutagenesis to remove two novel nuclear localization sequences, NLS-1 and -2,
      either alone or in combination (DNLS). Loss of NLS-1 or NLS-2 alone did not alter
      the nuclear targeting of MKP-2 but mutation of both resulted in MKP-2 being
      retained within the cytosol. Furthermore, whilst expression of WT-MKP-2, NLS-1 or
      NLS-2 reduced both sorbitol- or UV-stimulated nuclear c-Jun N-terminal kinase
      (JNK) activity in HEK293 cells, this effect was absent in cells expressing DNLS
      MKP-2. Similarly, transient transfection of WT-MKP-2, NLS-1 or NLS-2, but not
      DNLS-MKP-2 was able to substantially reduce agonist-stimulated ANF reporter
      activity in rat cardiac myocytes. Taken together, these results indicate that
      whilst both novel NLS participate in the nuclear localization of MKP-2, the
      expression of either sequence is sufficient to retain nuclear targeting.

PMID- 15722196
TI  - Direct interactions among Ret, GDNF and GFRalpha1 molecules reveal new insights
      into the assembly of a functional three-protein complex.
AB  - The glial-cell-line-derived neurotrophic factor (GDNF) ligand activates the Ret
      receptor through the assembly of a multiprotein complex, including the GDNF
      family receptor alpha1 (GFRalpha1) molecule. Given the neuroprotective role of
      GDNF, there is an obvious need to precisely identify the structural regions
      engaged in direct interactions between the three molecules. Here, we combined a
      functional approach for Ret activity (in PC12 cells) to cross-linking experiments
      followed by MS-MALDI to study the interactions among the purified extracellular
      region of the human Ret, GDNF and GFRalpha1 molecules. This procedure allowed us
      to identify distinct regions of Ret that are physically engaged in the
      interaction with GDNF and GFRalpha1. The lack of these regions in a recombinant
      Ret form results in the failure of both structural and functional binding of Ret
      to GFRalpha1/GDNF complex. Furthermore, a model for the assembly of a transducing
      competent Ret complex is suggested.

PMID- 15722197
TI  - NF-kappaB overrides the apoptotic program of TNF receptor 1 but not CD40 in
      carcinoma cells.
AB  - The activation of NF-kappaB and phosphatidylinositol-3 (PI3) kinase by TNF-alpha
      and TRAIL overrides the pro-apoptotic effects of these ligands in carcinoma cells
      and hinders their therapeutic application. In this report we show that CD40
      ligand, another member of the TNF superfamily, also triggers the activation of
      these signalling pathways but, importantly, utilises only the PI3 kinase cascade
      for anti-apoptotic responses, inasmuch as suppression of PI3 kinase but not NF
      kappaB sensitises carcinoma cells to CD40L-induced apoptosis. Therefore, NF
      kappaB activation does not always confer anti-apoptotic effects. Moreover, no
      cross-talk between the two pathways was observed, as the specific suppression of
      PI3 kinase with chemical inhibitors did not influence CD40-mediated IkappaBalpha
      phosphorylation and degradation or NF-kappaB binding and transactivation.
      Similarly, whilst suppression of Akt expression by RNA interference sensitised
      tumour cells to CD40L-induced apoptosis, it had no effect on CD40-mediated
      IkappaBalpha degradation. These data provide new evidence for the role of NF
      kappaB and PI3 kinase/Akt in phenotypic effects mediated by CD40 ligation and
      highlight differences in the mechanisms by which TNF family members regulate
      apoptosis in carcinoma cells.

PMID- 15722198
TI  - Effects of extracellular nucleotides in the thyroid: P2Y2 receptor-mediated
      ERK1/2 activation and c-Fos induction in PC Cl3 cells.
AB  - Aim of the present paper was to investigate the signaling pathways of P2Y2 in rat
      thyroid PC Cl3 cell line and its effects on proliferation. This study
      demonstrates that P2Y2 activation provoked: (a) a cytosol-to-membrane
      translocation of PKC-alpha, -betaI and -epsilon; (b) the phosphorylation of the
      extra cellular signal-regulated kinases 1 and 2 (ERK1/2); (c) the expression of c
      Fos protein; (d) no effects on the G1/S progression and overall cell
      proliferation. The P2Y2-stimulated ERK1/2 phosphorylation was: (a) completely
      blocked by PD098059, a mitogen-activated protein kinase (MEK) inhibitor or by W
      7, a Ca2+-calmodulin (CaM) antagonist; (b) reduced by GF109203X, inhibitor of
      PKCs, or AG1478, inhibitor of EGFR tyrosine kinase, or LY294002/wortmannin,
      inhibitors of phosphoinositide 3-kinases, or cytochalasin D, inhibitor of actin
      microfilament bundles polymerization. The c-Fos induction was greatly diminished
      by Go6976 or PD098059, and completely abolished when combined. In conclusion,
      data indicate that the P2Y2-induced phosphorylation of ERK1/2 and the induction
      of c-Fos are due to the operation of CaM, with PKC, PI3K, EGFR and receptor
      endocytosis mechanisms endorsing the signalling. On the other hand, no mitogenic
      effects of P2Y2 are whatsoever noticed in PC Cl3 cells.

PMID- 15722199
TI  - The subcellular localization control of integrin linked kinase 1 through its
      protein-protein interaction with caveolin-1.
AB  - Integrin linked kinase 1 (ILK1), a member of the serine/threonine kinases, has
      been shown to be crucial for the cell survival, differentiation, and Wnt
      signaling. Firstly, by using a confocal microscopy and a transfection approach,
      we obtained the evidence that ILK1 interacts physically with caveolin-1, a 22-kDa
      integral membrane protein, which is the principal structural and regulatory
      component of caveolae membranes. By ILK1 deletion mutant analysis, we
      characterized the caveolin-1-binding domain in the kinase domain of ILK1. In
      addition, we found that native ILK1 is associated with endogenous caveolin-1 in
      COS-1 cells. Secondly, transient transfection assays showed that a reduction in
      caveolin-1 binding leads to a substantial increase in the serine/threonine
      phosphorylation of ILK1. Thirdly, caveolin-1 and its scaffolding peptide (amino
      acids 82-101) functionally suppressed the auto-kinase activity of purified
      recombinant ILK1 protein. Fourthly, the association of ILK1 with caveolin-1
      regulated its cytoplasmic retention; if it was not associated with caveolin-1, it
      was transported to the nucleus. Fifthly, we also noticed the putative nuclear
      localization sequences (nls) in ILK1 near the caveolin-1-binding domain. Thus,
      our data indicate that caveolin-1 regulates ILK1 auto-phosphorylation activity
      and its subcellular localization via a specific protein-protein interaction
      through blocking the exposure of its putative nls motif.

PMID- 15722200
TI  - The human stress-activated protein kinase-interacting 1 gene encodes JNK-binding
      proteins.
AB  - The orthologous proteins of the stress-activated protein kinase-interacting 1
      (Sin1) family have been implicated in several different signal transduction
      pathways. In this study, we have investigated the function of the full-length
      human Sin1 protein and a C-terminally truncated isoform, Sin1alpha, which is
      produced by alternative splicing. Immunoblot analysis using an anti-Sin1
      polyclonal antibody showed that full-length Sin1 and several smaller isoforms are
      widely expressed. Sin1 was demonstrated to bind to c-Jun N-terminal kinase (JNK)
      in vitro and in vivo, while no interaction with p38- or ERK1/2-family MAPKs was
      observed. The Sin1alpha isoform could also form a complex with JNK in vivo.
      Despite localizing in distinct compartments within the cell, both Sin1 and
      Sin1alpha co-localized with JNK, suggesting that the Sin1 proteins could recruit
      JNK. Over-expression of full-length Sin1 inhibited the activation of JNK by UV-C
      in DG75 cells, as well as basal JNK-activity in HEK293 cells. These data suggest
      that the human Sin1 proteins may act as scaffold molecules in the regulation of
      signaling by JNK.

PMID- 15722201
TI  - Differential regulation of insulin receptor substrate-1 degradation during
      mannitol and okadaic acid induced apoptosis in human neuroblastoma cells.
AB  - Insulin receptor substrate (IRS) proteins are major docking molecules for the
      type I insulin like growth factor (IGF) receptor (IGF-IR) and mediate their
      effects on downstream signaling molecules. In this report, we investigated IRS-1
      regulation during apoptosis in human neuroblastoma SH-EP cells. Treatment of SH
      EP cells with mannitol or okadaic acid (OA) induces apoptosis with the typical
      characteristics of anoikis. Mannitol treatment results in IRS-1 degradation with
      concomitant appearance of smaller fragments, likely representing caspase cleavage
      products. In contrast OA-induced IRS-1 degradation is accompanied by a mobility
      shift in IRS-1, suggesting IRS-1 serine/threonine phosphorylation. Mannitol
      induced, but not OA-induced, degradation is blocked by IGF-I. Pretreatment of the
      cells with caspase or proteasome inhibitors also partially blocks mannitol
      induced IRS-1 degradation. These results suggest two independent pathways are
      involved in IRS-1 degradation; one pathway is dependent on caspase activation and
      is blocked by IGF-I, while a second pathway is caspase-independent and IGF-I
      insensitive.

PMID- 15722202
TI  - Sphingosylphosphorylcholine generates reactive oxygen species through calcium-,
      protein kinase Cdelta- and phospholipase D-dependent pathways.
AB  - Sphingosylphosphorylcholine (SPC) is a bioactive lipid molecule involved in
      numerous biological processes. Treatment of MS1 pancreatic islet endothelial
      cells with SPC increased phospholipase D (PLD) activity in a time- and dose
      dependent manner. In addition, treatment of the MS1 cells with 10 microM SPC
      induced stimulation of phospholipase C (PLC) activity and transient elevation of
      intracellular Ca2+. The SPC-induced PLD activation was prevented by pretreatment
      of the MS1 cells with a PLC inhibitor, U73122, and an intracellular Ca2+
      chelating agent, BAPTA-AM. This suggests that PLC-dependent elevation of
      intracellular Ca2+ is involved in the SPC-induced activation of PLD. The SPC
      dependent PLD activity was also almost completely prevented by pretreatment with
      pan-specific PKC inhibitors, GF109203X and RO-31-8220, and with a PKCdelta
      specific inhibitor, rottlerin, but not by pretreatment with GO6976, a
      conventional PKC isozymes-specific inhibitor. Adenoviral overexpression of a
      kinase-deficient mutant of PKCdelta attenuated the SPC-induced PLD activity.
      These results suggest that PKCdelta plays a crucial role for the SPC-induced PLD
      activation. The SPC-induced PLD activation was preferentially potentiated in COS
      7 cells transfected with PLD2 but not with PLD1, suggesting a specific
      implication of PLD2 in the SPC-induced PLD activation. SPC treatment induced
      phosphorylation of PLD2 in COS-7 cells, and overexpression of the kinase
      deficient mutant of PKCdelta prevented the SPC-induced phosphorylation of PLD2.
      Furthermore, SPC treatment generated reactive oxygen species (ROS) in MS1 cells
      and the SPC induced production of ROS was inhibited by pretreatment with U73122,
      BAPTA-AM, and rottlerin. In addition, pretreatment with a PLD inhibitor 1-butanol
      and overexpression of a lipase-inactive mutant of PLD2 but not PLD1 attenuated
      the SPC-induced generation of ROS. These results suggest that PLC-, Ca2+-,
      PKCdelta-, and PLD2-dependent pathways are essentially required for the SPC
      induced ROS generation.

PMID- 15722203
TI  - What is novel in the novelty oddball paradigm? Functional significance of the
      novelty P3 event-related potential as revealed by independent component analysis.
AB  - To better understand whether voluntary attention affects how the brain processes
      novel events, variants of the auditory novelty oddball paradigm were presented to
      two different groups of human volunteers. One group of subjects (n=16) silently
      counted rarely presented 'infrequent' tones (p=0.10), interspersed with 'novel'
      task-irrelevant unique environmental sounds (p=0.10) and frequently presented
      'standard' tones (p=0.80). A second group of subjects (n=17) silently counted the
      'novel' environmental sounds, the 'infrequent' tones now serving as the task
      irrelevant deviant events. Analysis of event-related potentials (ERPs) recorded
      from 63 scalp channels suggested a spatiotemporal overlap of fronto-central
      novelty P3 and centro-parietal P3 (P3b) ERP features in both groups. Application
      of independent component analysis (ICA) to concatenated single trials revealed
      two independent component clusters that accounted for portions of the novelty P3
      and P3b response features, respectively. The P3b-related ICA cluster contributed
      to the novelty P3 amplitude response to novel environmental sounds. In contrast
      to the scalp ERPs, the amplitude of the novelty P3 related cluster was not
      affected by voluntary attention, that is, by the target/nontarget distinction.
      This result demonstrates the usefulness of ICA for disentangling spatiotemporally
      overlapping ERP processes and provides evidence that task irrelevance is not a
      necessary feature of novelty processing.

PMID- 15722204
TI  - Sleep inertia: performance changes after sleep, rest and active waking.
AB  - Napping benefits and sustains subsequent performance. Prophylactic naps have been
      recommended as a means to maintain performance during extended wakefulness, as
      required during shiftwork. However, napping may cause short-term performance
      impairments, because awakening from sleep is followed by sleep inertia, a period
      of hypovigilance and impaired cognitive and behavioral performance. We
      investigated sleep inertia after an afternoon nap. Healthy 18-28 year-olds (n=50,
      not sleep deprived) were assigned to sleep, active wake or rest groups for a 2-h
      experimental phase with polysomnography starting either at 14:00 or 16:00 for
      half of each group. Before (baseline, 12:30 or 14:30) and in five sessions during
      the hour after the experimental phase (16:00-17:00 or 18:00-19:00), subjects
      completed an addition task, an auditory reaction time task, and the Stanford
      Sleepiness Scale. In session one, addition speed in the sleep group was reduced
      compared with baseline and with active wake controls, whereas calculation
      accuracy did not change. Addition speed in the sleep and rest groups increased
      substantially from session one to session two and reached a level similar to that
      of the active wake group by the fifth session. In the first session, auditory
      reaction speed of the sleep group was reduced compared with baseline and with
      rest controls but did not differ from the active wake group. The slowest reaction
      times showed significant recovery after 20 min. The groups reported similar
      increases in subjective sleepiness after the experimental period. These findings
      provide evidence for performance slowing and recovery during the hour following a
      2-h nap opportunity. They highlight the importance of employing multiple control
      groups and various objective and subjective measures to assess sleep inertia.

PMID- 15722205
TI  - Spatio-temporal dynamics of top-down control: directing attention to location
      and/or color as revealed by ERPs and source modeling.
AB  - This study investigated the nature and dynamics of the top-down control
      mechanisms that afford attentional selection using event-related potentials
      (ERPs) and dipole-source modeling. Subjects performed a task in which they were
      cued to direct attention to color, location, a conjunction of color and location
      or no specific feature on a trial-by-trial basis. Overall, similar ERP patterns
      were observed for directing attention to color and location, suggesting that
      spatial and non-spatial attention rely to a great extent on similar control
      mechanisms. The earliest attention-directing effect, at 340 ms, was localized to
      ventral posterior cortex and may reflect processes by which the cue is linked to
      its associated feature. Only late in the cue-target interval, differences in ERP
      were observed between directing attention to color and location. These originated
      from anterior and ventral posterior areas and may represent differences in,
      respectively, maintenance and perceptual biasing processes. The ventral posterior
      sources estimated for these late effects of directing attention to location and
      color were located posterior to those estimated for the modulatory effects of,
      respectively, spatial and non-spatial attention. This suggests that the precise
      neural populations involved in perceptual biasing and attentional modulation may
      differ. Conjunction cues initially elicited less posterior positivity than color
      and location cues, but evoked greater central positivity from 540 ms on. This
      central effect may reflect feature integration or ongoing processes related to
      cue-symbol translation. These results extend our understanding of the spatio
      temporal dynamics of top-down attentional control.

PMID- 15722206
TI  - A structural equation modeling analysis of attentional control: an event-related
      fMRI study.
AB  - We report here the first investigation of the effective connectivity between
      neural structures supporting attentional control using structural equation
      modeling and functional magnetic resonance imaging (fMRI). Attentional control
      was examined by employing a modified version of the flanker task. We found that
      the inconsistent condition elicited a significantly greater number of path
      coefficients than the consistent condition. In addition, we report that the
      strength of the prefrontal paths common to both conditions were not different,
      but that the remaining six paths were different between conditions. Importantly,
      these results suggest that the relationship between regions supporting
      attentional control differ between task conditions but the strength of the
      relationship between some prefrontal regions is invariant between task
      conditions. Additionally, we found that the paths were significantly lateralized
      to the right hemisphere. These results are discussed in relation to theories of
      the function of each region in attentional control.

PMID- 15722207
TI  - Brain mappings of the arithmetic processing in children and adults.
AB  - Despite the increasing number of experimental mapping showing that human
      arithmetic cognition is supported by widely spread neural circuits; the
      theoretical reasoning about these data remains mostly metaphorical and guided by
      a connectionist approach. Although neurons at distinct areas in the brain are
      assumed to take charge of different duties in the solution of the experimental
      task, the results are always discussed by hypothesizing some association between
      the different areas without questioning any difference of behavior at the level
      of the neurons at each of these areas. Here, the brain is assumed as Distributed
      Intelligent Processing System (DIPS) formed by collections of loosely interacting
      specialized agents (neurons), each agent specializing, for example, in data
      collection (sensors), problem solving (associative neurons), data communication
      (interneuronal systems) and in acting upon the surrounding environment
      (motorneurons). A new technique for EEG brain mapping is proposed and used to
      study arithmetic cognition in elementary school aged children and adults. Factor
      analysis showed three distinct patterns of neuronal recruitment for arithmetic
      calculations in all experimental groups which varied according to the type of
      calculation, age and sex.

PMID- 15722208
TI  - Learning-related fMRI activation associated with a rotational visuo-motor
      transformation.
AB  - The unique ability to learn transformed or altered visuo-motor relationships
      during motor learning (visuo-motor transformation learning) has engaged
      researchers for over a century. Compared to other forms of motor learning (e.g.,
      sequence learning), little is known about plasticity in the cortical and/or
      subcortical systems involved. We used fMRI to isolate region-specific activation
      changes during the learning of a visuo-motor (joystick) task under a simple
      transformation (90 degree rotation of visual feedback). Distributed brain systems
      were engaged in the learning process. In particular, we found evidence of a
      learning-dependent transition from early activation of the posterior parietal
      cortex to later distributed cortico-subcortical-cerebellar responses (in the
      temporal and occipital cortices, basal ganglia, cerebellum and thalamus). The
      role of the posterior parietal cortex may relate specifically to the acquisition
      of the transformation, while that of the fusiform and superior temporal gyri may
      reflect higher level visual and visuo-spatial processing underlying
      consolidation. Learning-related increases in cerebellar responses are consistent
      with its proposed role in the acquisition of internal models of the motor
      apparatus. These learning-related changes suggest a role for interacting neural
      systems involving the co-operation of cortico-cortico, cortico-cerebellar and
      cortico-basal ganglia loops during visuo-motor transformation learning.

PMID- 15722209
TI  - The sensorimotor transformation of cross-modal spatial information in the
      anterior intraparietal sulcus as revealed by functional MRI.
AB  - The parietal cortex in monkeys and humans has been shown to play an important
      role in the transformation of sensory information to motor commands. However, it
      is still unclear whether in humans, these areas are divided functionally into
      subregions based on different combinations of sensory and motor modalities. To
      identify subregions in the parietal cortex involved in the sensorimotor
      information transformation between different modalities, functional MRI was used
      to examine brain areas activated during tasks requiring different sensorimotor
      transformations--i.e., various combinations of eye (saccade) or finger movements
      triggered by visual or somatosensory cues. We then compared the activations
      between cross-modal conditions (eye movements triggered by somatosensory cues and
      finger movements triggered by visual cues) and intramodal (eye movements
      triggered by visual cues and finger movements triggered by somatosensory cues)
      conditions. Although the parietal cortex was involved in all tasks regardless of
      sensorimotor combinations, the only region activated to a greater degree in the
      cross-modal conditions compared to the intramodal conditions was the anterior
      portion of the intraparietal sulcus (a-IPS). The results suggest that the a-IPS
      plays an important role in the sensorimotor transformation of cross-modal spatial
      information.

PMID- 15722210
TI  - The neural substrate of arithmetic operations and procedure complexity.
AB  - Recent functional neuroimaging studies have begun to clarify how the human brain
      performs the everyday activities that require mental calculation. We used fMRI to
      test the hypotheses that there are specific neural networks dedicated to
      performing an arithmetic operation (e.g. + or -) and to performing processes that
      support more complex calculations. We found that the right inferior parietal
      lobule, left precuneus and left superior parietal gyrus are relatively specific
      for performing subtraction; and bilateral medial frontal/cingulate cortex are
      relatively specific for supporting arithmetic procedure complexity. We also found
      that greater difficulty level was associated with activation in a brain network
      including left inferior intraparietal sulcus, left inferior frontal gyrus and
      bilateral cingulate. Our results suggest that the network activated by the
      simplest calculation serves as a common basis, to which more regions are
      recruited for more difficult problems or different arithmetic operations.

PMID- 15722211
TI  - ERP effects of the processing of syntactic long-distance dependencies.
AB  - In behavioral studies on sentence comprehension, much evidence indicates that
      shorter dependencies are preferred over longer dependencies, and that longer
      dependencies incur a greater processing cost. However, it remains uncertain which
      of the various steps involved in the processing of long-distance dependencies is
      responsible for the increased cost of longer dependencies. Previous sentence
      comprehension studies using event-related potentials (ERPs) have revealed
      response components that reflect the construction [J. King, M. Kutas, Who did
      what and when? Using word- and clause-level ERPs to monitor working memory usage
      in reading. Journal of Cognitive Neuroscience, 7, (1995) 376-395.] and completion
      [E. Kaan, A. Harris, E. Gibson, P. Holcomb, The P600 as an index of syntactic
      integration difficulty. Language and Cognitive Processes, 5, (2000) 159-201.] of
      long-distance wh-dependencies. This article reports one off-line rating study and
      one ERP study that manipulated both the presence of wh-dependencies and the
      length of the dependencies (one clause vs. two clauses), with the aim of
      clarifying the locus of length-sensitivity and the functional role of associated
      ERP components. Results of the off-line study confirm that longer wh-dependencies
      incur greater processing cost. Results of the ERP study indicate that both a
      sustained anterior negativity that follows the initiation of the wh-dependency
      and also a late posterior positivity (P600) that marks the completion of the
      dependency are sensitive to the presence of a wh-dependency, but do not show
      amplitude variations reflecting the length of the dependency. However, the P600
      is delayed when it marks the completion of a longer wh-dependency. This suggests
      that both the sustained negativity and the P600 reflect length-insensitive
      aspects of the construction of syntactic dependencies. In addition, an N400
      component is elicited in the middle of the two clause wh-dependency, upon
      encountering a verb with an argument structure that prevents completion of the
      dependency.

PMID- 15722212
TI  - The interfering effect of related events on recognition memory discriminability:
      a functional magnetic resonance imaging study.
AB  - Retrieval of information from memory often involves the selection of an event
      among competing related events, a process that frequently gives rise to
      interference effects. The present study used a forced-choice recognition test to
      identify neural correlates of the interfering effect of related events on
      recognition memory discriminability. Participants encoded landscape pictures
      divided into three segments. One segment was presented during encoding, and a
      forced-choice recognition task contrasted a studied and a nonstudied segment for
      each landscape. For half of the landscapes, the third segment was presented
      between encoding and recognition tasks to induce associative interference by
      reducing recognition discriminability. A behavioral study with 40 subjects
      yielded a significant difference in the correct recognition rate between control
      and interference trials (76% and 64%, respectively, p<0.001). A subsequent event
      related fMRI study with 16 subjects yielded significant activations for correct
      interference recognition trials relative to control trials in left superior
      parietal regions, which suggests that these regions play a role in the
      representation of stimuli and associated information. The opposite contrast
      yielded significant activations in inferior prefrontal regions bilaterally, right
      dorsolateral prefrontal cortex and right parahippocampal cortex. Since this
      contrast was conducted using only correctly recognized trials, these findings
      could reflect an index of memory discriminability or saliency which could
      influence conscious recollection.

PMID- 15722213
TI  - fMRI evidence of word frequency and strength effects during episodic memory
      encoding.
AB  - Word frequency (WF) and strength effects are two important phenomena associated
      with episodic memory. The former refers to the superior hit-rate (HR) for low
      (LF) compared to high frequency (HF) words in recognition memory, while the
      latter describes the incremental effect(s) upon HRs associated with repeating an
      item at study. Using the "subsequent memory" method with event-related fMRI, we
      tested the attention-at-encoding (AE) [M. Glanzer, J.K. Adams, The mirror effect
      in recognition memory: data and theory, J. Exp. Psychol.: Learn Mem. Cogn. 16
      (1990) 5-16] explanation of the WF effect. In addition to investigating encoding
      strength, we addressed if study involves accessing prior representations of
      repeated items via the same mechanism as that at test [J.L. McClelland, M.
      Chappell, Familiarity breeds differentiation: a subjective-likelihood approach to
      the effects of experience in recognition memory, Psychol. Rev. 105 (1998) 724
      760], entailing recollection [K.J. Malmberg, J.E. Holden, R.M. Shiffrin, Modeling
      the effects of repetitions, similarity, and normative word frequency on judgments
      of frequency and recognition memory, J. Exp. Psychol.: Learn Mem. Cogn. 30 (2004)
      319-331] and whether less processing effort is entailed for encoding each
      repetition [M. Cary, L.M. Reder, A dual-process account of the list-length and
      strength-based mirror effects in recognition, J. Mem. Lang. 49 (2003) 231-248].
      The increased BOLD responses observed in the left inferior prefrontal cortex
      (LIPC) for the WF effect provide support for an AE account. Less effort does
      appear to be required for encoding each repetition of an item, as reduced BOLD
      responses were observed in the LIPC and left lateral temporal cortex; both
      regions demonstrated increased responses in the conventional subsequent memory
      analysis. At test, a left lateral parietal BOLD response was observed for studied
      versus unstudied items, while only medial parietal activity was observed for
      repeated items at study, indicating that accessing prior representations at
      encoding does not necessarily occur via the same mechanism as that at test, and
      is unlikely to involve a conscious recall-like process such as recollection. This
      information may prove useful for constraining cognitive theories of episodic
      memory.

PMID- 15722214
TI  - Response repetition vs. response change modulates behavioral and
      electrophysiological effects of distraction.
AB  - If stimulation occasionally contains distracting information, behavioral
      responses to task-relevant aspects of the stimulation are prolonged and more
      error prone. Additionally, event-related potentials (ERPs) acquired in an
      auditory distraction paradigm show that the distracting information elicits the
      components mismatch negativity (MMN), P3a and reorienting negativity (RON). Here,
      we assess to what extent sequential dependencies in the stimulation influence
      such indicators of distraction. Data of four experiments were reanalyzed for
      response repetition and response change trials separately. Behavioral performance
      on Deviants suggests markedly smaller distraction effects in change compared to
      repetition trials. However, the presence of MMN-P3a-RON in both response
      repetition and response change trials shows that sequential features in
      stimulation do not dissolve distraction, but might substantially contribute to
      the (behavioral) effects measured in distraction paradigms and should be
      controlled for.

PMID- 15722215
TI  - Neural representations of graspable objects: are tools special?
AB  - Recent cognitive and neuroimaging studies have examined the relationship between
      perception and action in the context of tools. These studies suggest that tools
      "potentiate" actions even when overt actions are not required in a task. Tools
      are unique objects because they have a visual structure that affords action and
      also a specific functional identity. The present studies investigated the extent
      to which a tool's representation for action is tied to its graspability or its
      functional use. Functional magnetic resonance imaging (fMRI) was used to examine
      the motor representations associated with different classes of graspable objects.
      Participants viewed and imagined grasping images of 3D tools with handles or
      neutral graspable shapes. During the viewing task, motor-related regions of
      cortex (posterior middle temporal gyrus, ventral premotor, and posterior
      parietal) were associated with tools compared to shapes. During the imagined
      grasping task, a frontal-parietal-temporal network of activation was seen with
      both types of objects. However, differences were found in the extent and location
      of premotor and parietal activation, and additional activation in the middle
      temporal gyrus and fusiform gyrus for tools compared to shapes. We suggest that
      the functional identity of graspable objects influences the extent of motor
      representations associated with them. These results have implications for
      understanding the interactions between "what" and "how" visual processing
      systems.

PMID- 15722216
TI  - Electrophysiological study of contextual variations in a short-term face
      recognition task.
AB  - Event-related potentials (ERPs) were recorded during two short-term recognition
      tasks using unfamiliar faces. These experiments are based on the process
      dissociation procedure (PDP), whereby the exclusion criterion was an intrinsic
      context or extrinsic context, the facial expression (Experiment 1) or background
      (Experiment 2), respectively. The results indicate that retrieval orientation, in
      addition to extensive strategic control, affects both the frontal (N250) and
      temporoparietal (P3b) components. Furthermore, these data indicate that an early
      frontal modulation interacts between processing that bears on the face
      (interactive intrinsic context) and processing that bears on two objects at the
      same time (interactive extrinsic context), in which, in the latter case, that the
      background change led to an early modulation at the frontal sites in the left
      hemisphere. These results are consistent with the idea that frontal effects
      reflect differences in the nature of the information during retrieval and
      postretrieval processes involved. Furthermore, that the left posterior repetition
      effect appears to be a manifestation of the retrieval of relevant contextual
      information that perturbs the recognition decision, whereas the right posterior
      repetition effect reflects to be the outcome of the retrieval of the face as a
      whole. Finally, results are in concordance with the hypothesis that the
      difference during recognition with or without source memory may be in the
      strength of the relationship between the target and the contextual information to
      be retrieved. In essence, that automatic and controlled processes in a given
      context depends on both task-related and target-related constraints.

PMID- 15722217
TI  - Mass spectrometry in proteomics.

PMID- 15722218
TI  - Mass spectrometry of peptides and proteins.
AB  - This tutorial article introduces mass spectrometry (MS) for peptide fragmentation
      and protein identification. The current approaches being used for protein
      identification include top-down and bottom-up sequencing. Top-down sequencing, a
      relatively new approach that involves fragmenting intact proteins directly, is
      briefly introduced. Bottom-up sequencing, a traditional approach that fragments
      peptides in the gas phase after protein digestion, is discussed in more detail.
      The most widely used ion activation and dissociation process, gas-phase collision
      activated dissociation (CAD), is discussed from a practical point of view.
      Infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD)
      are introduced as two alternative dissociation methods. For spectral
      interpretation, the common fragment ion types in peptide fragmentation and their
      structures are introduced; the influence of instrumental methods on the
      fragmentation pathways and final spectra are discussed. A discussion is also
      provided on the complications in sample preparation for MS analysis. The final
      section of this article provides a brief review of recent research efforts on
      different algorithmic approaches being developed to improve protein
      identification searches.

PMID- 15722219
TI  - Informatics for protein identification by mass spectrometry.
AB  - High throughput protein analysis (i.e., proteomics) first became possible when
      sensitive peptide mass mapping techniques were developed, thereby allowing for
      the possibility of identifying and cataloging most 2D gel electrophoresis spots.
      Shortly thereafter a few groups pioneered the idea of identifying proteins by
      using peptide tandem mass spectra to search protein sequence databases. Hence, it
      became possible to identify proteins from very complex mixtures. One drawback to
      these latter techniques is that it is not entirely straightforward to make
      matches using tandem mass spectra of peptides that are modified or have sequences
      that differ slightly from what is present in the sequence database that is being
      searched. This has been part of the motivation behind automated de novo
      sequencing programs that attempt to derive a peptide sequence regardless of its
      presence in a sequence database. The sequence candidates thus generated are then
      subjected to homology-based database search programs (e.g., BLAST or FASTA).
      These homology search programs, however, were not developed with mass
      spectrometry in mind, and it became necessary to make minor modifications such
      that mass spectrometric ambiguities can be taken into account when comparing
      query and database sequences. Finally, this review will discuss the important
      issue of validating protein identifications. All of the search programs will
      produce a top ranked answer; however, only the credulous are willing to accept
      them carte blanche.

PMID- 15722220
TI  - Peptide mass fingerprinting.
AB  - Peptide mass fingerprinting by MALDI-MS and sequencing by tandem mass
      spectrometry have evolved into the major methods for identification of proteins
      following separation by two-dimensional gel electrophoresis, SDS-PAGE or liquid
      chromatography. One main technological goal of proteome analyses beside high
      sensitivity and automation was the comprehensive analysis of proteins. Therefore,
      the protein species level with the essential information on co- and post
      translational modifications must be achieved. The power of peptide mass
      fingerprinting for protein identification was described here, as exemplified by
      the identification of protein species with high molecular masses (spectrin alpha
      and beta), low molecular masses (elongation factor EF-TU fragments), splice
      variants (alpha A crystallin), aggregates with disulfide bridges
      (alkylhydroperoxide reductase), and phosphorylated proteins (heat shock protein
      27). Helpful tools for these analyses were the use of the minimal protein
      identifier concept and the software program MS-Screener to remove mass peaks
      assignable to contaminants and neighbor spots.

PMID- 15722221
TI  - Protein identification using 2D-LC-MS/MS.
AB  - Multidimensional liquid chromatography techniques have been coupled to tandem
      mass spectrometry to provide a robust method to identify proteins in complex
      mixtures. Data acquisition is interfaced directly with search algorithms for
      identification through cross-correlation with databases. This review describes
      the most recent advances in methodologies for protein identification by mass
      spectrometry and describes the limitations of the application of the
      technologies.

PMID- 15722222
TI  - Analysis of protein phosphorylation by mass spectrometry.
AB  - The reversible phosphorylation of proteins is recognized as an essential post
      translational modification regulating cell signaling and ultimately function of
      biological systems. Detection of phosphopeptides and localization of
      phosphorylation sites remains quite a challenge, even if the protein is purified
      to near homogeneity. Mass spectrometry has become a vital technique that is
      routinely utilized for the identification of proteins from whole cell lysates.
      Nonetheless, due to the minimal amount of phosphorylation found on proteins,
      enrichment steps for isolating phosphopeptides from complex mixtures have been
      the focus of many research groups world-wide. In this review, we describe some
      current methods for the enrichment of phosphopeptides that are compatible with
      mass spectrometry for assignment of phosphorylation sites. Phosphorylation
      modifications on proteins and peptides are either directly isolated by solid
      phase approaches or chemically modified for selective isolation and/or improved
      characterization by mass spectrometry. These strategies hold the potential for
      rapid and sensitive profiling of phosphoproteins from a variety of sources and
      cellular conditions.

PMID- 15722223
TI  - The absolute quantification strategy: a general procedure for the quantification
      of proteins and post-translational modifications.
AB  - Advances in biological mass spectrometry have resulted in the development of
      numerous strategies for the large-scale quantification of protein expression
      levels within cells. These measurements of protein expression are most commonly
      accomplished through differential incorporation of stable isotopes into cellular
      proteins. Several variations of the stable isotope quantification method have
      been demonstrated, differing in isotope composition and incorporation strategy.
      In general, the majority of these methods establish only relative quantification
      of expressed proteins. To address this, the absolute quantification (AQUA)
      strategy was developed for the precise determination of protein expression and
      post-translational modification levels. The AQUA method relies on the use of a
      synthetic internal standard peptide that is introduced at a known concentration
      to cell lysates during digestion. This AQUA peptide precisely mimics a peptide
      produced during proteolysis of the target protein, except that it is enriched in
      certain stable isotopes. Analysis of the proteolyzed sample by a selected
      reaction monitoring (SRM) experiment in a tandem mass spectrometer results in the
      direct detection and quantification of both the native peptide and isotope
      labeled AQUA internal standard peptide. As an example, the development and
      application of a method to measure a tryptic peptide representing the amount of
      polyubiquitin chain formation through lysine 48 (K48) is presented. The
      simplicity and sensitivity of the method, coupled with the widespread
      availability of tandem mass spectrometers, make the AQUA strategy a highly useful
      procedure for measuring the levels of proteins and post-translational
      modifications directly from cell lysates.

PMID- 15722225
TI  - Biomarker discovery in biological fluids.
AB  - Discovery of novel protein biomarkers is essential for successful drug discovery
      and development. These novel protein biomarkers may aid accelerated drug
      efficacy, response, or toxicity decision making based on their enhanced
      sensitivity and/or specificity. These biomarkers, if necessary, could eventually
      be converted into novel diagnostic marker assays. Proteomic platforms developed
      over the past few years have given us the ability to rapidly identify novel
      protein biomarkers in various biological matrices from cell cultures (lysates,
      supernatants) to human clinical samples (serum, plasma, and urine). In this
      article, we delineate an approach to biomarker discovery. This approach is
      divided into three steps, (i) identification of markers, (ii) prioritization of
      identified markers, and (iii) preliminary validation (qualification) of
      prioritized markers. Using drug-induced idiosyncratic hepatotoxicity as a case
      study, the article elaborates methods and techniques utilized during the three
      steps of biomarker discovery process. The first step involves identification of
      markers using multi-dimensional protein identification technology. The second
      step involves prioritization of a subset of marker candidates based on several
      criteria such as availability of reagent set for assay development and literature
      association to disease biology. The last step of biomarker discovery involves
      development of preliminary assays to confirm the bio-analytical measurements from
      the first step, as well as qualify the marker(s) in pre-clinical models, to
      initiate future marker validation and development.

PMID- 15722224
TI  - Purifying protein complexes for mass spectrometry: applications to protein
      translation.
AB  - Proteins control and mediate most of the biological activities in the cell. In
      most cases, proteins either interact with regulatory proteins or function in
      large molecular assemblies to carryout biological processes. Understanding the
      functions of individual proteins requires the identification of these interacting
      proteins. With its speed and sensitivity, mass spectrometry has become the
      dominant method for identifying components of protein complexes. This article
      reviews and discusses various approaches to purify protein complexes and analyze
      the proteins using mass spectrometry. As examples, methods to isolate and analyze
      protein complexes responsible for the translation of messenger RNAs into
      polypeptides are described.

PMID- 15722226
TI  - Integrating gene and protein expression data: pattern analysis and profile
      mining.
AB  - Proteomics and functional genomics are emerging new research fields devoted to
      the study of the entire collection of proteins and mRNA transcripts (collectively
      known as gene products) that define a biological system. DNA microarrays are now
      a popular platform for measuring changes in messenger RNA transcript levels on a
      genome-wide scale, while gel-free shotgun profiling methods based on tandem mass
      spectrometry are increasingly being used to determine the identity, modification
      states, and relative abundance of large numbers of proteins. By defining the
      behavior of entire biological pathways and networks under various physiological
      states, these studies aim to extend traditional reductionist molecular genetic
      approaches regarding the biological roles of the vast array of uncharacterized
      gene products. A key goal is to determine how the information encoded by the
      myriad of expressed gene products is integrated at the molecular, cellular, and
      even whole organism level to create the dynamic biochemical processes and complex
      physiological controls that sustain life. While comparison of the complementary
      information contained in proteomic and mRNA data sets poses considerable
      analytical challenges, these efforts should provide added insight into the
      fundamental mechanisms underlying physiology, development, and the emergence of
      disease. Here, we outline several analytical approaches, methods, and tools that
      have proven to be helpful in the face of this important challenge.

PMID- 15722227
TI  - Side effects in sea bass (Dicentrarchus labrax L.) due to intraperitoneal
      vaccination against vibriosis and pasteurellosis.
AB  - Sea bass (Dicentrarchus labrax L.) were injected intraperitoneally with
      monovalent (Photobacterium damselae subsp. piscicida or Vibrio anguillarum) and
      divalent (Ph. damselae subsp. piscicida and V. anguillarum) vaccine formulations,
      with or without adjuvants (mineral oil, liposome or alginate), to evaluate the
      short and long-term pathological effects. Eight animals from each group were
      sampled one, two, four and 11 months after intraperitoneal injection. The acute
      peritoneal response and the progression to a chronic status were evaluated by
      analysing peritoneal leucocytes collected during the first days post-injection.
      To evaluate the chronic response, the late peritoneal leucocyte response was
      analysed and the peritoneal cavity was examined and the intra-abdominal lesion
      level scored based on a pre-defined scale. Correlation between leucocyte
      exudative response, tissue inflammatory response and the development of granuloma
      were sought. The acute leucocyte response was characterized by an early (24-48 h)
      mobilization of neutrophils and macrophages, with phagocyte numbers dependent on
      the formulation, but no significant variations were observed in lymphocytes/small
      cells and EGCs. Later on, a steady increase occurred in lymphocytes/small cells
      and EGCs and a high concentration in neutrophils and macrophages was maintained
      up to 30-60 days in groups i.p. injected with oil adjuvanted formulations with
      antigen. All the lesions observed were moderate, indicating that in sea bass, the
      pathological effects due to intraperitoneally injected vaccines are less severe
      than in other fish species. The divalent oil adjuvanted vaccine induced the most
      severe side effects, with macroscopic granulomas consistently present up to 11
      months.

PMID- 15722228
TI  - Characterisation of monoclonal antibodies to haemocyte types of scallop (Chlamys
      farreri).
AB  - Four monoclonal antibodies (MAbs) (1E7, 1F12, 2H5, 2C6) against haemocytes of
      scallop (Chlamys farreri) were produced by immunising Balb/C mice. Analysed by
      the indirect immunofluorescence assay test (IIFAT), immunocytochemical assay,
      flow cytometry (FCM) and Western-blotting, they showed specificity for more than
      one haemocyte type (hyalinocyte and granulocyte) and various haemocyte components
      of scallop. Using IIFAT to detect monolayers separated from gradient density
      centrifugation, the four MAbs were positive with haemocytes at different
      interfaces. The percentage of positive cells (percent reactivity, PR) that MAb
      1E7 reacted with at the 20-30%, 30-40% and 40-50% interfaces were 43.50%, 41.25%
      and 60.00% respectively, PR of MAb 1F12 were 31.00%, 63.50% and 41.00%, MAb 2C6
      were 11.00%, 51.00%, 77.00%, and MAb 2H5 were 20.25%, 34.75%, 38.25%. For the
      immunocytochemical assay, MAb 1E7 1F12 and 2H5 was positive with the cytoplasm of
      both hyalinocyte and granulocyte, 2C6 was positive with the membrane and
      cytoplasm of hyalinocyte and granulocyte. Analysed by FCM, the PR of the four
      MAbs (1E7, 1F12, 2H5, 2C6) with haemocytes were 54.23%, 38.56%, 56.4%, and 79.7%
      respectively; moreover, the PR with different haemocyte types was variable. The
      results of Western-blotting showed that MAb 1E7 recognised an antigen of
      molecular weight 200 kDa, MAb 2C6 an antigen of 60 kDa, however, MAb 1F12 reacted
      with antigens of 70 kDa, 60 kDa and 45 kDa. There was no protein band that MAb
      2H5 detected. In conclusion, 2C6 seems to be a very promising MAb to identify and
      differentiate granulocytes, and the four MAbs will be used in further studies on
      cellular defence mechanism research.

PMID- 15722230
TI  - Systemic priming of alloreactive cytotoxic cells in carp, following anal
      administration of allogeneic cell antigens.
AB  - In the present study, we confirmed that cellular immune responses, especially
      specific cell-mediated cytotoxicity, could be induced in systemic carp
      leucocytes, following anal administration of antigens. Effector cells isolated
      from systemic lymphoid tissues (head kidney, spleen and peripheral blood) of carp
      that were immunised anally with allogeneic cells (EPC or KG cell line)
      efficiently lysed immunogenic target cells. The lytic activity was increased as a
      result of secondary sensitisation and peaked around 7 days after the final
      immunisation. In some aspects, the alloantigen-specific cell-mediated
      cytotoxicity induced by anal sensitisation was different from that induced by
      intraperitoneal (i.p.) injection. First, the activity induced by anal
      immunisation was higher than that resulting from i.p. immunisation when fish were
      immunised twice with a 7-day interval, whereas similar kinetics of the
      cytotoxicity were observed after the final immunisation. Second, repeated anal
      administrations tended to decrease the cytotoxic activity, although repeated i.p.
      injections increased the activity. These findings indicate that the anal
      administration of antigens in fish can elicit and modulate cellular immune
      responses.

PMID- 15722229
TI  - Time course study of in situ expression of antigens following DNA-vaccination
      against VHS in rainbow trout (Oncorhynchus mykiss Walbaum) fry.
AB  - The present study was performed as a time course study of fish vaccinated with 20
      microg plasmid DNA vaccine encoding either the VHSV G-protein or the VHSV N
      protein. Samples of the injection site were collected sequentially over a 7-week
      period. The study revealed an intense positive staining by immunohistochemistry
      for the viral G-protein mainly in the membrane of intact myocytes, most prominent
      by days 10-27, and with concomitant infiltration of inflammatory cells by days 13
      38 that subsequently lead to a marked reduction in the number of myocytes
      expressing the G-protein. By immunofluorescence, infiltrating cells positive for
      MHC II, IgM, and C3 were demonstrated. By contrast, in fish vaccinated with the
      VHSV-N construct, fewer, diffusely positive myocytes were found, most prominent
      by days 13-38, these having a positive reaction for the N-protein mainly in the
      cytoplasm and variably in the membrane. N-protein positive myocytes did not
      attract infiltrating cells to the same degree. Positive reaction for the N
      protein almost ceased by day 48 post-vaccination.

PMID- 15722231
TI  - Cloning of the Atlantic salmon (Salmo salar) IL-1 receptor associated protein.
AB  - In mammals, the pro-inflammatory cytokine interleukin-1 signals through a
      receptor complex containing a type I interleukin-1 receptor (IL-1RI) and a
      receptor associated protein (IL-1RAcP). Previously, we have described a cDNA from
      Atlantic salmon encoding a molecule with homology to the mammalian IL-RI. This
      molecule was named IL-1 receptor like protein (IL-1RLP) in the absence of
      functional data to support its proposed role as the salmon IL-1RI. Here, we
      describe the cloning and characterisation of a cDNA encoding salmon IL-1RAcP.
      Like other members of the IL-1R family, the salmon IL-1RAcP encodes three
      extracellular immunoglobulin-like domains and a cytoplasmic Toll/Interleukin-1
      receptor (TIR) domain involved in signalling. Specific binding of salmon IL-1RAcP
      to IL-1RLP was shown by co-immunoprecipitation studies.

PMID- 15722232
TI  - Dietary administration of Lactobacillus delbrueckii and Bacillus subtilis, single
      or combined, on gilthead seabream cellular innate immune responses.
AB  - The effects of oral administration of Lactobacillus delbrueckii ssp. lactis and
      Bacillus subtilis, single or combined, on gilthead seabream cellular innate
      immune responses were investigated. Fish were fed four different diets: control
      (non-supplemented); or diet supplemented with 10(7) cfu g(-1)L. delbrueckii ssp.
      lactis; 10(7) cfu g(-1)B. subtilis; or with 0.5x10(7) cfu g(-1)L. delbrueckii
      ssp. lactis and 0.5x10(7) cfu g(-1)B. subtilis. This feeding regime lasted for 3
      weeks, and all experimental groups were then fed the control commercial diet for
      another week. Six fish were sampled at weeks 1, 2, 3 and 4. Head-kidney
      leucocytes were isolated and the main cellular innate immune parameters
      (leucocyte peroxidase content, phagocytosis, respiratory burst activity and
      cytotoxicity) were evaluated. Leucocyte peroxidase content was lower in all
      groups at week 3 but the levels tended to recover during the last week of the
      experiment. Respiratory burst activity was not affected at any time of the
      experiment in any of the experimental groups. However, phagocytic activity
      increased after 2 weeks of feeding the single bacteria-supplemented diets,
      whereas the combination of the two caused an increment which persisted for as
      long as the bacteria were being administered. Cytotoxic activity was also
      significantly increased after 3 weeks of feeding the mixture of the two bacteria.
      After 1 week back on the control diet, the parameters in the experimental groups
      had recovered or even dropped below those recorded in the control group,
      suggesting that the bacteria did not persist in the seabream gut.

PMID- 15722233
TI  - Induction of antiviral state in fish cells by Japanese flounder, Paralichthys
      olivaceus, interferon regulatory factor-1.
AB  - Interferon regulatory factor-1 (IRF-1) mediates an antiviral state in cells by
      regulating the expression of the interferon (IFN-alpha/beta) system. To elucidate
      the role of IRF-1 in fish during virus infections, we constructed a recombinant
      plasmid of the Japanese flounder, Paralichthys olivaceus IRF-1 (JF IRF-1) under
      the control of the cytomegalovirus (CMV) immediate/early enhancer promoter. The
      antiviral mechanism of JF IRF-1 was studied using transfection experiments in a
      homologous cell line. Here, we show that cell supernatants obtained from
      transiently transfected cells enhanced cell viability of a heterologous cell line
      upon incubation, reduced the titers of hirame rhabdovirus (HIRRV) and viral
      hemorrhagic septicemia virus (VHSV), and possessed cytokine-like activity, as
      shown by their ability to protect cells against virus infections. The
      supernatants also inhibited the replication of the rhabdoviruses during the early
      stages of infection as indicated by the reduction of viral titers in the presence
      of the supernatants obtained from the transfected cells. Further analysis showed
      that the cell culture supernatants contain cytokine-like substances that possess
      acid-labile and temperature-resistant properties. These results indicate that JF
      IRF-1 induces an antiviral state in cells by mediating the production of cytokine
      like substances. Thus, JF IRF-1 might be useful as an adjuvant in the development
      of DNA vaccines against commercially important viral pathogens in Japanese
      flounder aquaculture.

PMID- 15722234
TI  - Hemagglutinating and antibacterial activities of vitellogenin.

PMID- 15722237
TI  - Radiographic evaluation of esophageal function.
AB  - Radiologic studies can be helpful when evaluating patients who are suspected of
      having esophageal motility disorders. Performing studies of the highest technical
      quality yields the most definitive results. The esophagus should be assessed for
      anatomic and functional abnormalities that may account for presenting symptoms.
      Motility disorders such as achalasia and scleroderma have specific radiographic
      findings that are described in this article; however, some motility disorders of
      the esophagus have nonspecific radiographic findings. In those cases, it is
      imperative that clinical and manometric information be combined with radiographic
      findings to provide accurate diagnoses. The radiographic examinations that are
      most commonly used include barium esophagography and nuclear medicine
      examinations. This article emphasizes the use of barium examinations to assess
      esophageal motility.

PMID- 15722238
TI  - Manometry: technical issues.
AB  - Manometry involves many technical issues, and a complete understanding of all
      aspects of the esophageal testing process is required to study the human
      esophagus in a way that yields accurate, technically sound qualitative and
      quantitative studies that include the measure of esophageal length and positional
      plotting of transducers within the esophagus. Topics discussed are catheter
      measurement and memory; checking the system; performing manometry; patient
      history; intubation technique; marking, mapping, and measuring the esophagus, and
      analysis of results.

PMID- 15722239
TI  - Multichannel intraluminal impedance: general principles and technical issues.
AB  - Multichannel intraluminal impedance (MII) is a new technology that allows
      detection of bolus movement without the use of external radiation or radiolabeled
      substances. The principles of MII are based on changes in resistance to
      alternating electrical current (impedance) induced by the presence of various
      boluses within the esophagus. The timing of changes in multiple impedance
      measuring segments in the esophagus allows determination of the direction of
      bolus movement. Combined MII and manometry (MII-EM) provides simultaneous
      information on intraesophageal pressures and bolus transit, offers the ability to
      monitor all types of reflux, and allows the detection of the physical (liquid,
      gas, or mixed) and chemical (acid, nonacid) characteristics of the
      gastroesophageal refluxate.

PMID- 15722240
TI  - Esophageal function testing: role of combined multichannel intraluminal impedance
      and manometry.
AB  - Combined multichannel intraluminal impedance and manometry (MII-EM) is a
      relatively new technique that allows simultaneous measurement of intraesophageal
      pressures and bolus transit. Combined MII-EM has the ability to identify what
      percentage of manometric normal/peristaltic, ineffective, and simultaneous
      swallows have complete or incomplete bolus transit. Predictors of normal bolus
      transit in patients with ineffective esophageal motility are the distal
      esophageal amplitude, the number of sites with low amplitudes, and the overall
      number of manometric ineffective contractions. Outcome studies are necessary to
      evaluate whether combined MII-EM is superior to traditional manometry in
      evaluating patients with nonobstructive dysphagia and in identifying patients at
      risk for developing dysphagia after antireflux surgery.

PMID- 15722241
TI  - Use of intragastric pH monitoring in gastroesophageal reflux disease.
AB  - Prolonged intragastric pH monitoring is a valuable technique for evaluating head
      to-head comparisons of the antisecretory effects of different pharmacologic
      agents, for studying the effects of higher doses of proton pump inhibitors (PPIs)
      on daytime and nighttime pH control, for evaluating the effects of dose timing in
      relation to a meal on the intragastric pH response to these antisecretory agents,
      and for examining interindividual variability in individual pH response to PPIs
      taken orally. Measuring intragastric pH has helped immeasurably in understanding
      the efficacy of PPIs and is especially useful in the clinical arena to guide the
      management of patients across the spectrum of gastroesophageal reflux disease.

PMID- 15722242
TI  - Catheter-based pH monitoring: use in evaluation of gastroesophageal reflux
      disease symptoms (on and off therapy).
AB  - Tube-based ambulatory pH testing has rapidly evolved in the past 3 decades to
      become the standard by which other diagnostic approaches to gastroesophageal
      reflux disease are judged. Acid exposure 5 cm above the manometrically determined
      lower esophageal sphincter is the standard for documentation of pathologic acid
      exposure of the distal esophagus. Proximal esophageal or hypopharyngeal
      monitoring is an evolving technique that may shed light on patients with
      supraesophageal symptoms. The ability to simultaneously monitor esophageal and
      gastric acidity (usually in patients with persistent symptoms despite therapy) is
      another advantage of this technique. Whether the new system that allows
      simultaneous pH and impedance monitoring and the system that uses an implantable
      tubeless monitoring capsule will supplant this older but well-established
      technology remains to be determined.

PMID- 15722243
TI  - Prolonged pH monitoring: Bravo capsule.
AB  - The Bravo pH monitoring system is a safe and well-tolerated reliable method for
      measuring esophageal acid exposure. Key potential advantages of this system are
      related to its ability to be unobtrusive, comfortable, and provide study periods
      of longer duration. These advantages make it an excellent option for subjects who
      are unwilling or unable to tolerate conventional catheter pH monitoring. Whether
      the Bravo capsule improves diagnostic accuracy is still unclear; however, initial
      results are promising and further validation studies are expected. Whether this
      method is preferred over conventional monitoring for diagnostic evaluation
      depends on multiple considerations ranging from cost to possible
      contraindications for both systems. Further refinements in methodology and
      recording protocol are likely to be made, which will improve diagnostic accuracy
      and lower cost.

PMID- 15722244
TI  - The role of pH monitoring in extraesophageal gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is linked to several extraesophageal
      disease states including laryngitis, asthma, chronic cough, and noncardiac chest
      pain (NCCP). Although 24-hour pH monitoring is considered the "gold standard" in
      the diagnosis of typical GERD, it is also increasingly used in establishing the
      diagnosis of GERD in patients with extraesophageal symptoms. The clinical utility
      of pH monitoring in this patient population, however, remains controversial. In
      this article, the authors examine the role of pH monitoring in laryngitis,
      asthma, chronic cough, and NCCP.

PMID- 15722245
TI  - Evaluation of esophageal function/pH in endoscopic therapy for gastroesophageal
      reflux disease.
AB  - Gastroesophageal reflux disease (GERD) typically requires lifelong medical
      therapy or surgery for the management of patients with frequent symptoms. The
      current standard of care is to prescribe medical therapy using proton pump
      inhibitors. Patients with moderate-to-severe GERD require extended/maintenance
      therapy. Until recently, the only alternative to this approach was surgical
      intervention. Endoscopic therapy for GERD has emerged as a second alternative
      strategy. Primary endpoints for all interventions have aimed at symptomatic
      control and reduction/discontinuance of medication use. For surgical and
      endoscopic therapies, however, there are other physiologic endpoints that have
      attempted to define changes in lower esophageal sphincter pressure and esophageal
      acid exposure. For patients being evaluated for endoscopic GERD therapy, the
      author recommends comprehensive esophageal testing and pH testing.

PMID- 15722246
TI  - Evaluation of esophageal function for antireflux surgery.
AB  - Antireflux surgery has become well established as an effective and durable
      therapy for gastroesophageal reflux disease and its complications. The outcome of
      antireflux surgery, however, is only as good as the evaluation to document the
      association between pathologic esophageal acid exposure and the patient's
      symptoms. This article discusses the well-established diagnostic modalities used
      to assess foregut structure and function and includes several more sophisticated
      secondary studies that may aid the clinician in elucidating the cause of the
      problem in patients in whom standard testing is inadequate.

PMID- 15722247
TI  - Reflux monitoring: role of combined multichannel intraluminal impedance and pH.
AB  - Combined multichannel intraluminal impedance and pH (MII-pH) is a promising
      technique that identifies liquid, gas, and mixed gastroesophageal reflux and
      categorizes it into acid and nonacid types. Gastroesophageal monitoring using
      combined MII-pH reconfirms previously reported data that there is a difference
      between refluxate volume presence time in the esophagus and time pH less than 4.
      Only one in five patients with persistent symptoms on acid-suppressive therapy
      have symptoms associated with persistent acid reflux, whereas two of five
      patients have symptoms associated with nonacid reflux; the remaining patients do
      not have any type of GER related to their symptoms. Combined MII-pH is a useful
      tool in evaluating patients with persistent symptoms on acid-suppressive therapy,
      patients with atypical symptoms, and infants.

PMID- 15722248
TI  - Early haemodynamic benefit of sildenafil in patients with coexisting chronic
      thromboembolic pulmonary hypertension and left ventricular dysfunction.
AB  - Sildenafil, a phosphodiesterase type-5 inhibitor, offers potential to treat
      pulmonary hypertension associated with a variety of conditions. We assessed the
      early impact of sildenafil on a cohort of patients referred to our unit who had
      severe pulmonary hypertension secondary to chronic thromboembolic disease which
      was not amenable to pulmonary thromboendarterectomy and who also had coexisting
      left ventricular dysfunction. Six patients were studied. Diagnosis of pulmonary
      embolic disease was made by ventilation perfusion scanning and/or CT pulmonary
      angiography. All patients were anticoagulated with oral coumarin derivatives and
      none were considered suitable for pulmonary thromboendarterectomy. Pulmonary
      hypertension was diagnosed by right heart catheterisation and each patient had
      Medical Research Council (MRC) dyspnoea score and New York Heart Association
      (NYHA) class noted and 2D echocardiography prior to commencement of sildenafil 50
      mg three times a day. After 6 weeks of sildenafil therapy, right heart
      catheterisation and 2D echocardiography were repeated, and MRC dyspnoea score,
      NYHA class and exercise capacity were recorded. All patients demonstrated an
      improvement in mean pulmonary artery pressure, mean pulmonary capillary wedge
      pressure, MRC dyspnoea score, NYHA class and gas transfer. No adverse effects of
      sildenafil were noted. Our data suggests that sildenafil is an effective and well
      tolerated therapy for patients with severe pulmonary hypertension associated with
      pulmonary thromboembolic disease and impaired left ventricular function,
      producing beneficial effects as early as 6 weeks.

PMID- 15722249
TI  - Pharmacologic properties of YM218, a novel, potent, nonpeptide vasopressin V1A
      receptor-selective antagonist.
AB  - The pharmacologic profile of YM218, (Z)-4'-{4,4-difluoro-5-[2-oxo-2-(4
      piperidinopiperidino)ethylidene]-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl}
      2-methyl-3-furanilide hemifumarate, a newly synthesized, nonpeptide vasopressin
      (AVP) receptor antagonist, was investigated using several in vitro and in vivo
      methods. YM218 exhibited high affinity for V1A receptors isolated from rat liver,
      with a Ki value of 0.50 nM. In contrast, YM218 exhibited much lower affinity for
      rat pituitary V1B, kidney V2, and uterus oxytocin receptors, with Ki values of
      1510 nM, 72.2 nM, and 150 nM, respectively. In vivo studies revealed that YM218
      dose-dependently inhibited pressor response to exogenous AVP in pithed rats
      (intravenous) and in conscious normotensive rats (intravenous or oral) with a
      long duration of action (>8 h at 3 mg/kg, p.o.). In contrast, oral administration
      of YM218 did not increase urine excretion in conscious rats. These results
      demonstrate that YM218 is a potent nonpeptide AVP V1A receptor-selective
      antagonist that will be useful in future studies to help clarify the physiologic
      and pathophysiologic roles of AVP.

PMID- 15722250
TI  - Creatine kinase isoenzyme patterns upon chronic exposure to cigarette smoke:
      protective effect of Bacoside A.
AB  - Cigarette smoking is implicated as a major risk factor in the development of
      cardiovascular and cerebrovascular diseases. Creatine kinase (CK) and its
      isoforms (CK-MM, MB, BB) have been advocated as sensitive markers in the
      assessment of cardiac and cerebral damage. Therefore, in the present study, we
      report the isoenzyme patterns of CK in rats upon exposure to cigarette smoke and
      the protective effect of Bacoside A against chronic smoking induced toxicity.
      Adult male albino rats were exposed to cigarette smoke and simultaneously
      administered with Bacoside A, the active constituent from the plant Bacopa
      monniera, for a period of 12 weeks. The activity of CK was assayed in serum,
      heart and brain, and its isoenzymes in serum were separated electrophoretically.
      Rats exposed to cigarette smoke showed significant increase in serum CK activity
      with concomitant decrease in heart and brain. Also cigarette smoke exposure
      resulted in a marked increase in all the three isoforms in serum. Administration
      of Bacoside A prevented these alterations induced by cigarette smoking. Cigarette
      smoking is known to cause free radical mediated lipid peroxidation leading to
      increased membrane permeability and cellular damage in the heart and brain
      resulting in the release of CK into the circulation. The protective effect of
      Bacoside A on the structural and functional integrity of the membrane prevented
      the leakage of CK from the respective tissues, which could be attributed to its
      free radical scavenging and anti-lipid peroxidative effect.

PMID- 15722251
TI  - Activation of alpha2-adrenoceptors is necessary to induce nitric oxide release in
      isoprenaline-induced relaxation.
AB  - The aim of this study was to investigate the role of the contractile agent on the
      relaxation induced by isoprenaline and the contribution of nitric oxide (NO) and
      cGMP to this relaxation. These studies were conducted in intact endothelium or
      denuded aortas contracted with the EC50 of norepinephrine (NE) or phenylephrine
      (Phe), and the relaxation induced by isoprenaline (non-selective beta
      adrenoceptor agonist) or forskolin (activator of adenylyl-cyclase) was studied.
      The maximum effect (Emax) and pD2 were analysed. Isoprenaline and forskolin
      induced relaxation were not changed by the endothelium removal in both NE and Phe
      contracted aortas. However, L-NAME reduced the relaxation induced by isoprenaline
      (Emax from 94.48+/-2.30%, n=7 to 66.17+/-11.73%, n=7; pD2 from 7.56+/-0.10 to
      6.08+/-0.15) only in NE-contracted aortas. The pD2 of isoprenaline was also
      reduced by ODQ (6.57+/-0.13), but not the Emax. The inhibitory effects of L-NAME
      and ODQ were reversed by yohimbine. L-NAME, ODQ and oxyhemoglobin had no effect
      on the relaxation induced by isoprenaline in Phe-contracted aortas. Taken
      together, these results suggest that norepinephrine, a non-selective alpha
      adrenoceptor agonist can also activate alpha2-adrenoceptors sensitive to
      yohimbine in the endothelial cells, activating the NO-synthase and cGMP
      production which would potentiate the relaxation induced by isoprenaline.
      However, this pathway is not activated with Phe, the selective alpha1
      adrenoceptors agonist.

PMID- 15722252
TI  - Effect of ionophore monensin on anaesthetized dogs in hemorrhagic hypotension.
AB  - AIM: Progressive decompensation and irreversible cellular injury from the severe
      hemorrhagic shock can be reversed therapeutically with aggressive and timely
      resuscitation by administering volume expanding fluids. The possibility of the
      use of rapidly acting pressor agents which can effectively maintain the blood
      pressure and peripheral perfusion (without volume resuscitation) and prevent the
      progression of shock and providing in regular time interval for volume
      replacement has not been looked into. In the present investigation, two pressor
      agents, dopamine and a long acting carboxylic ionophore monensin, were examined
      for their potential role in hemorrhagic hypotension produced experimentally in
      dogs. METHODS: Two groups of animals were studied: (a) In the first group (n=10)
      20% of the total blood volume i.e. moderate hemorrhage was induced. (b) In the
      second group (n=10) 35% of the total blood volume i.e. severe hemorrhage was
      induced. After 30 min of induction of hemorrhage both the groups were given
      intravenous infusion of dopamine (20 microgm/kg/min) for 10 min. Then after 30
      min of stopping dopamine infusion, both the groups were given intravenously a
      single bolus dose (50 microgm/kg) of monensin. RESULTS: In both moderate and
      severe hemorrhage monensin injection produced significant increases in systolic
      arterial blood pressure, mean arterial blood pressure, cardiac output and stroke
      volume. The effects persisted for 1 h of administration. In severe hemorrhage
      dopamine infusion produced significant decrease in mean arterial blood pressure,
      diastolic blood pressure and pH. Dopamine produced a significant rise in heart
      rate also while monensin did not have such an effect. CONCLUSION: Monensin
      produced a rapid and sustained recovery of the arterial blood pressure without
      requiring adequate preload. Dopamine failed to produce such an effect because it
      requires adequate circulating blood volume for its pressor action. Thus monensin
      has the potential to prevent progression of shock and improving the prognosis in
      management of hemorrhagic hypotension.

PMID- 15722253
TI  - Vaccines in the 21st century: the genetic response and the innocent bystander.

PMID- 15722255
TI  - Autoimmune hazards of hepatitis B vaccine.
AB  - According to Hippocratic tradition, the safety level of a preventive medicine
      must be very high, as it is aimed at protecting people against diseases that they
      may not contract. This paper points out that information on the safety of
      hepatitis B vaccine (HBV) is biased as compared to classical requirements of
      evidence-based medicine (EBM), as exemplified by a documented selectivity in the
      presentation or even publication of available clinical or epidemiological data.
      Then, a review is made of data suggesting that HBV is remarkable by the
      frequency, the severity and the variety of its complications, some of them
      probably related to a mechanism of molecular mimicry leading to demyelinating
      diseases, and the others reproducing the spectrum of non-hepatic manifestations
      of natural hepatitis B. To be explained, this unusual spectrum of toxicity
      requires additional investigations based upon complete release of available data.

PMID- 15722254
TI  - T cell immunity in hepatitis B and hepatitis C virus infection: implications for
      autoimmunity.
AB  - T cells are involved in the pathogenesis of important liver diseases including
      both autoimmune liver diseases and viral hepatitis. In addition to playing a
      crucial role in the control of hepatitis viruses, T cell responses are also
      responsible for the liver injury during acute and chronic phases of viral
      hepatitis. In this article, we reviewed current literature on T cell immunity to
      hepatitis B and C viruses. In addition, antigen presenting cells that are
      critical for T cell immunity against these viruses are also discussed. This will
      provide insights to the understanding of T cell immunity in autoimmune liver
      diseases due to the similar role of T cells in autoimmune liver diseases and
      viral hepatitis.

PMID- 15722256
TI  - Influenza, autoimmunity and atherogenesis.
AB  - It has been observed during influenza epidemics and in a number of population and
      clinical trials that this prevalent viral infection was associated with increased
      death rates from cardiovascular diseases. The clinical and experimental data that
      may explain accelerated coronary atherosclerosis in influenza infection with
      implications involving autoimmune mechanisms are reviewed in this article. Both
      cellular and humoral autoimmune mode could be proposed to participate in the
      onset or progression of atheromatous lesions due to influenza infection.

PMID- 15722258
TI  - Safety of hydroxychloroquine in pregnant patients with connective tissue
      diseases. Review of the literature.
AB  - Hydroxychloroquine (HCQ) is widely used in the treatment of systemic lupus
      erythematosus (SLE). Even if it is generally agreed that pregnancy per se
      increases disease activity in patients with SLE and that withdrawal of HCQ at the
      onset of pregnancy may result in exacerbation of SLE, use of HCQ during pregnancy
      has remained controversial for a long time. Parke was the first to propose
      continuation of HCQ throughout gestation. Currently, more than 250 pregnancies
      resulting in live births have been reported and no increase in the rate of birth
      defects have been demonstrated. When studied, no retinal toxicity and ototoxicity
      have been found. Data concerning lactation and HCQ treatment are rare. However,
      the amount of HCQ received by children through lactation seems very low. In
      conclusion, HCQ should probably be maintained throughout pregnancy in patients
      with SLE and it does not seem necessary to advise against breastfeeding.

PMID- 15722257
TI  - Epstein-Barr virus etiology in rheumatoid synovitis.
AB  - The etiology of rheumatoid arthritis (RA) has remained unknown, although it has
      been investigated and speculated that both genetic and environmental components
      contribute to the cause of this disease. Epstein-Barr virus (EBV) has been a
      strong candidate about for over 25 years as environmental infectious agent(s).
      There are many circumstantial evidence for association between EBV and RA, but
      definite evidence is wanting. In present article, we review an increase
      circumstantial proof which has been investigated so far and demonstrate direct
      evidence for the presence of EBV in inflamed synovial cells in patients with RA
      and discuss on the recent finding of signaling lymphocytic-activation molecule
      (SLAM)-associated protein (SAP), which opened a new approach to understand on
      impaired function of cytotoxic T cell for EBV in patients with RA.

PMID- 15722259
TI  - Analysis of periodic fluctuations of the height of Swedish soldiers in 18th and
      19th centuries.
AB  - This paper investigates the periodicity of the adult height of Swedish soldiers
      of the 18th and 19th centuries using spectral analysis. The height data are left
      truncated due to the enforcement of minimum height requirement. Hence, we use a
      truncated regression model using maximum likelihood estimation. We isolate the
      various frequency components, assess their importance, and perform sensitivity
      analysis by means of fitting several alternative models.

PMID- 15722260
TI  - Mortality and socio-economic differences in Denmark: a competing risks
      proportional hazard model.
AB  - This paper explores how mortality is related to such socio-economic factors as
      education, occupation, skill level and income for the years 1992-1997 using an
      extensive sample of the Danish population. We employ a competing risks
      proportional hazard model to allow for different causes of death. This method is
      important as some factors have unequal (and sometimes opposite) influence on the
      cause-specific mortality rates. We find that the often-found inverse correlation
      between socio-economic status and mortality is to a large degree absent among
      Danish women who die of cancer. In addition, for men the negative correlation
      between socio-economic status and mortality prevails for some diseases, but for
      women we find that factors such as being married, income, wealth and education
      are not significantly associated with higher life expectancy. Marriage increases
      the likelihood of dying from cancer for women, early retirement prolongs survival
      for men, and homeownership increases life expectancy in general.

PMID- 15722261
TI  - Height and BMI of Italian immigrants to the USA, 1908-1970.
AB  - We analyze self-reported anthropometric data pertaining to 2140 adults who
      emigrated to the United States, mainly from southern Italy, between 1908-1928 and
      1960-1970. The mean height of immigrant men was 165.5 cm: they were taller than
      contemporary southern Italian men by 0.5-7.3 cm in different periods. The mean
      height of the Italian immigrant women born before 1952 was 157.6 cm, less than
      the national average. At the end of the 1990s, national women average height was
      162 cm, 159.5 cm for southern women. There were age-related increases of weight
      and BMI: overweight was more prevalent in the 40-49 years age category. In the
      male sample, the mean values of BMI were within the overweight range in all age
      classes. The prevalence of obesity was higher in the male sample than among US
      men, whereas it was virtually identical in the women's sample and much higher
      than the values reported for several European countries for the period 1970-1980.

PMID- 15722262
TI  - The height-for-age of Indian children.
AB  - The height for age of children is used as an indicator of the prevalence of
      undernutrition, i.e., 'stunting'. This study uses unit-record data on over 20,000
      rural children, from 16 states of India, to explain variations in their height
      for-age. Previous studies of children's heights have focused exclusively on the
      mean of the distribution of heights-for-age using ordinary least squares (OLS)
      regression. Instead, this paper uses quantile regression--which analyses
      different parts of the height for age distribution--and permits a richer set of
      conclusions to be drawn. The analysis shows the importance of locating
      malnourished children in terms of their place in the distribution of nutritional
      outcomes and, then, studying the differential impact of the determining variables
      on outcomes for children in different locations of the distribution.

PMID- 15722263
TI  - Treading water. The long-term impact of the 1998 flood on nutrition in
      Bangladesh.
AB  - Bangladesh was hit by the worst flood in over a century in the summer of 1998.
      Although many households were able to smooth consumption expenditure, not
      everyone was able to maintain adequate calorie consumption. As a consequence, the
      nutritional status of children in households that were more severely exposed to
      the flood deteriorated. We use a three round panel data set to investigate which
      households were better protected from longer term nutritional crises, and whether
      the health of flood-exposed children recovered to the level of those who were not
      exposed. The evidence suggests that children exposed to the flood were adversely
      affected by the shock to their health and did not recover within the survey
      period. The results also suggest that ex ante government programs were more
      effective than ex post interventions to protect the heath of children from the
      impact of the flood.

PMID- 15722264
TI  - Mortality recovery and stabilization in Kazakhstan, 1995-2001.
AB  - This paper documents both the extraordinary rise in mortality that accompanied
      economic deterioration in the former Soviet Republic of Kazakhstan, as well as
      the far more tentative recovery. Kazakhstan's multi-ethnic population also makes
      it possible to identify a large mortality disadvantage for those--especially
      working-age males--who are not of Kazakh ethnicity. There are also stark regional
      differences--mortality decline is underway in many areas with substantial
      economic recovery, while elsewhere there has been no discernable improvement.

PMID- 15722266
TI  - Human capital, wealth, and nutrition in the Bolivian Amazon.
AB  - We analyze anthropometric variables of a society of forager-horticulturalists in
      the Bolivian Amazon (Tsimane') in 2001-2002. Community variables (e.g.,
      inequality, social capital) explain little of the variance in anthropometric
      indices of nutritional status, but individual-level variables (schooling, wealth)
      are positively correlated with nutritional status. Dietary quality (foods high in
      animal proteins), access to foraging technology, and traditional knowledge of
      medicinal plants are related to better anthropometric indices.

PMID- 15722265
TI  - The Jewish-Arab divide in life expectancy in Israel.
AB  - Life expectancy at birth in Israel in 2001 was 77.7 years for males and 81.6
      years for females among Jews, and 74.5 and 77.8 years for males and females,
      respectively, among Israeli Arabs. In spite of vast improvements in health
      conditions of the two populations since Israel's statehood in 1948, persistent
      disparities in life expectancy between the two groups have challenged the Israeli
      socialized health care system. These disparities are influenced primarily by
      differences between the two population groups in infant and child mortality
      rates. This early study suggests that the distribution of life expectancy across
      localities in Israel reflects the distribution of those localities' socio
      economic condition index (not including health and medical care), and the
      distribution of medical services. The positive association between life
      expectancy and the index is pronounced, however, only within the Jewish
      population but not among Arabs. While there may be no significant difference in
      life expectancy among Jews and Arabs living in poorer communities, there are
      fewer Arabs living in relatively affluent communities. Thus, persistent higher
      concentration of poverty among Arabs than among Jews has sufficed to maintain the
      gap in life expectancy between them. In addition, however, there are population
      specific effects: wealth and education are more protective among Jews than among
      Arabs, while medical services are more protective among Arabs.

PMID- 15722267
TI  - When the heart is stopped for good: hypotension-bradycardia paradox revisited.
AB  - In vasovagal syncope, occurrence of bradycardia/asystole in the wake of
      hypotension has often been considered paradoxical. The major objective of this
      teaching module is to critically examine the pathophysiological mechanism and
      significance of the hypotension-bradycardia paradox unique to this condition. We
      narrate here how we discussed the pathophysiology of vasovagal syncope in a large
      classroom session attended by 275 doctors and medical students. A case study was
      used to describe the typical clinical presentation of vasovagal syncope. The
      pathophysiological mechanisms involved were then discussed systematically using a
      series of open-ended questions. We made it clear 1) that the occurrence of
      bradycardia or asystole in the face of acute severe hypotension is a mechanism to
      possibly minimize further blood loss, prevent myocardial damage, and increase
      ventricular filling; and 2) that fainting, which occurs as a consequence of this,
      is a homeostatic mechanism that serves to restore venous return and cerebral
      blood flow before blood pressure is normalized by neural reflex mechanisms.
      Eighty-four percent of participants reported that they were satisfied with the
      session. The information contained herein could be used to explain to any
      suitable audience the neural regulation of blood pressure in the face of acute
      severe hypotension and the pathophysiology of vasovagal syncope.

PMID- 15722268
TI  - Varying femoral tunnels between the anatomical footprint and isometric positions:
      effect on kinematics of the anterior cruciate ligament-reconstructed knee.
AB  - BACKGROUND: Knee kinematics and in situ forces resulting from anterior cruciate
      ligament reconstructions with 2 femoral tunnel positions were evaluated.
      HYPOTHESIS: A graft placed inside the anatomical footprint of the anterior
      cruciate ligament will restore knee function better than a graft placed at a
      position for best graft isometry. STUDY DESIGN: Controlled laboratory study.
      METHODS: Ten cadaveric knees were tested in response to a 134-N anterior load and
      a combined 10-N.m valgus and 5-N.m internal rotation load. A robotic universal
      force-moment sensor testing system was used to apply loads, and resulting
      kinematics were recorded. An active surgical robot system was used for
      positioning tunnels in 2 locations in the femoral notch: inside the anatomical
      footprint of the anterior cruciate ligament and a position for best graft
      isometry. The same quadrupled hamstring tendon graft was used for both tunnel
      positions. The 2 loading conditions were applied. RESULTS: At 30 degrees of knee
      flexion, anterior tibial translation in response to the anterior load for the
      intact knee was 9.8 +/- 3.1 mm. Both femoral tunnel positions resulted in
      significantly higher anterior tibial translation (position 1: 13.8 +/- 4.6 mm;
      position 2: 16.6 +/- 3.7 mm; P < .05). There was a significant difference between
      the 2 tunnel positions. At the same flexion angle, the anterior tibial
      translation in response to the combined load for the intact knee was 7.7 +/- 4.0
      mm. Both femoral tunnel positions resulted in significantly higher anterior
      tibial translation (position 1: 10.4 +/- 5.5 mm; position 2: 12.0 +/- 5.2 mm; P <
      .05), with a significant difference between the tunnel positions. CONCLUSION:
      Neither femoral tunnel position restores normal kinematics of the intact knee. A
      femoral tunnel position inside the anatomical footprint of the anterior cruciate
      ligament results in knee kinematics closer to the intact knee than does a tunnel
      position located for best graft isometry. CLINICAL RELEVANCE: Anatomical femoral
      tunnel position is important in reproducing function of the anterior cruciate
      ligament.

PMID- 15722269
TI  - Chondral defect repair after the microfracture procedure: a nonhuman primate
      model.
AB  - BACKGROUND: The extent and time course of chondral defect healing after
      microfracture in humans are not well described. Although most physicians
      recommend a period of activity and weightbearing restriction to protect the
      healing cartilage, there are limited data on which to base decisions regarding
      the duration of such restrictions. HYPOTHESIS: Evaluation of the status of
      chondral defect repair at different time points after microfracture in a primate
      model may provide a rationale for postoperative activity recommendations. STUDY
      DESIGN: Descriptive laboratory study. METHODS: Full-thickness chondral defects
      created on the femoral condyles and trochlea of 12 cynomolgus macaques were
      treated with microfracture and evaluated by gross and histologic examination at 6
      and 12 weeks. RESULTS: At 6 weeks, there was limited chondral repair and ongoing
      resorption of subchondral bone. By 12 weeks, the defects were completely filled
      and showed more mature cartilage and bone repair. CONCLUSION: In the primate
      animal model, significant improvements in the extent and quality of cartilage
      repair were observed from the 6- to 12-week time points after microfracture.
      CLINICAL RELEVANCE: The poor status of the defect repair at 6 weeks and the
      ongoing healing observed from the 6- to 12-week time points may indicate that the
      repair is vulnerable during this initial postoperative period. Assuming the goal
      of postoperative weightbearing and activity restriction in patients after
      microfracture is to protect immature repair tissue, this study lends support to
      extending such recommendations longer than 6 weeks.

PMID- 15722270
TI  - Posterior cruciate ligament revision reconstruction, part 1: causes of surgical
      failure in 52 consecutive operations.
AB  - BACKGROUND: Posterior cruciate ligament reconstructions have not shown uniformly
      predictable results in restoration of normal posterior tibial translation. The
      authors are unaware of any study that has assessed the causes of failure of these
      operations, and they investigated 52 prior unsuccessful posterior cruciate
      ligament procedures to determine the factors that contributed to failure of the
      operations. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors
      studied 52 prior failed posterior cruciate ligament surgeries that had been done
      in 41 knees (40 patients). Graft reconstructions had been done in 31 cases,
      primary repairs in 14, synthetic replacements in 4, and thermoplasties in 3.
      Medical records, operative notes, radiographs, and magnetic resonance imaging
      scans were reviewed, and a comprehensive knee examination was conducted. RESULTS:
      A single factor that caused the operations to fail was identified in 23 (44%) of
      52 operations, and multiple factors were identified in 29 (56%). The most common
      probable causes of failure were associated posterolateral ligament deficiency
      (40%), improper graft tunnel placement (33%), associated varus malalignment
      (31%), and primary suture repair (25%). Sixteen of 21 (76%) prior posterolateral
      ligament procedures had failed, as had 9 of 19 (47%) prior anterior cruciate
      ligament reconstructions. Twenty-nine knees (71%) presented with pain with
      activities of daily living. Thirty-four knees (83%) had compounding problems of
      joint arthritis, prior meniscectomy, associated ligament deficiencies, or varus
      malalignment. Posterior cruciate revision surgery was done in 22 knees (54%).
      Eleven knees (27%) had severe joint damage that contraindicated revision, and 8
      (19%) declined further operations. CONCLUSIONS: Failure to restore associated
      ligament instabilities and incorrect tunnel placement were major factors
      contributing to surgical failure. The results suggest the need for greater
      emphasis on the initial reconstruction in graft tunnel placement, correction of
      associated ligament instabilities, and correction of varus osseous malalignment.
      Failure of concurrent posterolateral ligament reconstructions was frequently
      encountered, suggesting the need for higher strength augmentation procedures or
      anatomical graft replacement.

PMID- 15722271
TI  - Predicting in vivo clinical performance of anterior cruciate ligament fixation
      methods from in vitro analysis: industrial tests of fatigue life and tolerance
      limits are more useful than other cyclic loading parameters.
AB  - BACKGROUND: Anterior cruciate ligament graft fixations experience cyclic loads in
      vivo. Present cyclic loading studies testing fixation use "incremental cycling,"
      "residual strength" protocols, or a combination. Industrial standards, however,
      rely on fatigue life testing and use tolerance limits to determine guaranteed
      minimum levels of cycles to failure. HYPOTHESIS: Industrial standards of fatigue
      life and lower tolerance limits provide a more conservative assessment of cycles
      to failure than do currently used cyclic loading models, and they facilitate
      interpretation of data toward clinical performance. STUDY DESIGN: Descriptive
      laboratory study. METHODS: Fatigue life curves and lower tolerance limits were
      calculated for porcine patellar tendon graft fixations that were tested to
      failure in single pulls or cycled to failure at 2 different load levels. A log
      curve was constructed so that the expected values at other load levels could be
      calculated. Comparison of a metal and a composite resorbable interference screw
      design was used as an example. RESULTS: Cycles to failure of both screw designs
      varied widely at each load level. The guaranteed minimum number of cycles
      calculated by tolerance limits was therefore much lower than the mean cycles to
      failure at any given load level. For example, at a load of 250 N, the predicted
      mean life for the composite screw and the metal screw was 2513 and 1490 cycles,
      respectively, whereas the 80/80 tolerance limits (the value that 80% could be
      expected to achieve with 80% confidence) were only 63 and 68 cycles,
      respectively. Small reductions in load level gave very large increases in
      minimally expected life. CONCLUSIONS: Fatigue testing of anterior cruciate
      ligament reconstructions better shows the wide variation between specimens and
      the large effect of load levels on expected life. Wide scatter makes mean levels
      over-optimistic and difficult to interpret. Tolerance limits give estimates that
      are more conservative and facilitate data interpretation. CLINICAL RELEVANCE: A
      method for testing and analyzing fatigue properties was presented, results of
      which are more readily interpreted to clinical practice.

PMID- 15722272
TI  - Fifth metatarsal Jones fracture fixation with a 4.5-mm cannulated stainless steel
      screw in the competitive and recreational athlete: a clinical and radiographic
      evaluation.
AB  - BACKGROUND: Fifth metatarsal Jones fractures are common in the athletic
      population. Optimal screw selection for operative treatment has not been
      determined. HYPOTHESIS: A 4.5-mm cannulated screw used for fixation of the fifth
      metatarsal Jones fractures in athletes is an effective treatment approach. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: The authors studied 23
      consecutive athletes (24 feet) who were treated surgically with a 4.5-mm
      cannulated screw for fifth metatarsal fractures (Jones fracture) with clinical
      and radiographic assessments. RESULTS: There have been no refractures to date.
      Clinical healing was 100%. The mean percentage healing as shown on radiographs
      was 98.9%, with a range of 90% to 100%. All athletes returned to sport at a mean
      time of 7.5 weeks (range, 10 days to 12 weeks). Two athletes experienced a
      "reinjury" without need for operative treatment. All athletes were recommended to
      wear orthoses until their competitive careers were completed. CONCLUSION:
      Fixation with a stainless steel 4.5-mm cannulated screw gives 100% clinical
      healing and near-100% healing as shown on radiographs. CLINICAL RELEVANCE: The
      4.5-mm cannulated screws can yield reliable and effective healing as evidenced by
      clinical assessment and radiographs of fifth metatarsal Jones fractures in
      athletes.

PMID- 15722273
TI  - Association of unilateral isthmic spondylolysis with lamina fracture in an
      athlete: case report and literature review.

PMID- 15722274
TI  - Arthroscopic assessment for intra-articular disorders in residual ankle
      disability after sprain.
AB  - BACKGROUND: After ankle sprain, there can be many causes of disability, the
      origins of which cannot be determined using standard diagnostic tools.
      HYPOTHESIS: Ankle arthroscopy is a useful tool in identifying intra-articular
      disorders of the talocrural joint in cases of residual ankle disability after
      sprain. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS:
      The authors gathered the independent diagnostic results of physical examination,
      standard mortise and lateral radiography, stress radiography of the talocrural
      joint, and magnetic resonance imaging for 72 patients with residual ankle
      disability lasting more than 2 months after injury (mean, 7 months after injury).
      They performed arthroscopic procedures and compared the double-blind results.
      RESULTS: In all cases, the arthroscopic results matched those of other means of
      diagnosis. In 14 cases, the arthroscopic approach exceeded the capabilities of
      the other methods. Including duplications, 39 patients (54.2%) had anterior
      talofibular ligament injuries, 17 patients (23.6%) had distal tibiofibular
      ligament injuries, 29 patients (40.3%) had osteochondral lesions, 13 patients
      (18%) had symptomatic os subfibulare, 3 patients (4.2%) had anterior impingement
      exostosis, and 3 patients (4.2%) had impingement due to abnormally fibrous bands.
      There were only 2 cases in which the cause of symptoms could not be detected by
      ankle arthroscopy, compared with 16 cases in which the cause of disability could
      not be detected using standard methods. In 3 cases (17.6%) of distal tibiofibular
      ligament injuries, 8 cases (27.6%) of osteochondral lesions, and all 3 cases
      (100%) of impingement of an abnormal fibrous band, ankle arthroscopy was the only
      method capable of diagnosing the cause of residual ankle pain after a sprain.
      CONCLUSION: The present results suggest that arthroscopy can be used to diagnose
      the cause of residual pain after an ankle sprain in most cases that are otherwise
      undiagnosable by clinical examination and imaging study.

PMID- 15722275
TI  - The diagnostic value of intracompartmental pressure measurement, magnetic
      resonance imaging, and near-infrared spectroscopy in chronic exertional
      compartment syndrome: a prospective study in 50 patients.
AB  - BACKGROUND: Patients with chronic exertional compartment syndrome have pain
      during exercise that usually subsides at rest. History and physical examination
      may raise suspicion of the syndrome; diagnosis is usually confirmed with
      intracompartmental pressure measurement after exercise. Studies have shown that
      magnetic resonance imaging and near-infrared spectroscopy have diagnostic ability
      in this syndrome. HYPOTHESIS: Magnetic resonance imaging and near-infrared
      spectroscopy can be used to diagnose chronic exertional compartment syndrome.
      STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Patients
      were enrolled if there was clinical suspicion of chronic exertional compartment
      syndrome, and a fasciotomy was performed based on this suspicion. Before
      fasciotomy, intracompartmental pressure, near-infrared spectroscopy, and magnetic
      resonance imaging data were collected during and after exercise on a treadmill.
      Near-infrared spectroscopy and intracompartmental pressure values were recorded
      in the same manner after fasciotomy. Retrospective proof that diagnosis of the
      syndrome had been correct was the absence of exertional complaints from the
      preoperative examination during exercise at postfasciotomy visit. RESULTS: Fifty
      patients (100 legs) participated in the prefasciotomy visit; 3 refused
      fasciotomy; 2 were lost to follow-up. Of 45 patients who completed the
      postfasciotomy visit, the diagnosis of chronic exertional compartment syndrome
      was retrospectively confirmed in 42 patients and discarded in 3 patients. The
      sensitivity for intracompartmental pressure (cutoff point, 35 mmHg) found in this
      study was 77% (67%-86%, exact 95% confidence interval), lower than estimates from
      the literature (93%). The sensitivity (previously defined cutoff) for near
      infrared spectroscopy was 85% (76%-92%, exact 95% confidence interval),
      validating the estimate found in the literature (85%). Sensitivity of magnetic
      resonance imaging was comparable to that of intracompartmental pressure and near
      infrared spectroscopy; associated specificity at a given sensitivity appeared to
      be lower with magnetic resonance imaging. CONCLUSION: This study validates the
      sensitivity of near-infrared spectroscopy and provides estimates for the
      sensitivity and specificity of magnetic resonance imaging in chronic exertional
      compartment syndrome in a large group of patients. The sensitivity of noninvasive
      near-infrared spectroscopy is clinically equivalent to that of invasive
      intracompartmental pressure measurements.

PMID- 15722276
TI  - Percutaneous drilling of symptomatic accessory navicular in young athletes.
AB  - BACKGROUND: Results of percutaneous drilling for symptomatic type II accessory
      tarsal navicular bone are not determined. HYPOTHESIS: Percutaneous drilling of
      accessory navicular synchondrosis will induce or accelerate bone union between
      the accessory and primary navicular bones. Bone union of the synchondrosis leads
      to symptomatic relief. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Thirty-one feet of 29 patients with type II accessory tarsal navicular treated by
      percutaneous drilling were reviewed. RESULTS: Twenty-four feet (77.4%) were
      assessed as excellent, 6 (19.4%) as good, and 1 (3.2%) as fair. No feet were
      assessed as poor. Bone union was obtained in 16 (80%) of the 20 feet when the
      proximal phalanx of the great toe was immature and in 2 of the 11 feet when it
      was mature. CONCLUSION: Percutaneous drilling of the synchondrosis was effective
      for a symptomatic type II accessory navicular, especially in patients with
      immature proximal phalanx of the great toe.

PMID- 15722277
TI  - The effects of thermal capsular shrinkage on the outcomes of arthroscopic
      stabilization for primary anterior shoulder instability.
AB  - BACKGROUND: The effectiveness of arthroscopic thermal capsulorrhaphy in the
      prevention of recurrent instability in primary anterior stabilization is
      undetermined. PURPOSE: To determine if patients with recurrent anterior shoulder
      instability who have labral repair plus arthroscopic thermal capsulorrhaphy have
      better outcomes than those with labral repair alone. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHOD: There were 72 patients who underwent arthroscopic
      anterior shoulder stabilization with Suretac II tacks (n = 32) during 1996 to
      1999 or with Suretac II tacks plus arthroscopic radiofrequency capsular shrinkage
      (n = 40) from 1999 to 2002. Standardized patient-determined and examiner
      determined outcome measures were obtained preoperatively and at 3, 6, 12, and 24
      months postoperatively. Statistical analyses included a Kaplan-Meier analysis of
      time to recurrent instability. RESULTS: Of the 72 patients, 66 had complete
      follow-up, including 28 patients treated with the Suretac stabilization and 38
      patients with the Suretac plus radiofrequency shrinkage, for a mean follow-up of
      58 and 30 months, respectively. All patients had a Bankart lesion. Both groups
      had similar results with respect to patient-determined and examiner-determined
      outcome measures. The only adverse outcome was postoperative recurrent
      instability in 6 of 28 cases in the Suretac group alone and 8 of 38 cases in the
      Suretac-plus -shrinkage group. Most recurrent instability occurred between 6 and
      24 months. Kaplan-Meier analysis for time to recurrent instability showed no
      differences in the rate of instability recurrence between the 2 groups.
      CONCLUSION: Arthroscopic thermal capsulorrhaphy neither enhanced nor impaired the
      outcomes of arthroscopic labral repair with biodegradable tacks in patients with
      primary recurrent anterior shoulder instability.

PMID- 15722278
TI  - Posterior cruciate ligament revision reconstruction, part 2: results of revision
      using a 2-strand quadriceps tendon-patellar bone autograft.
AB  - BACKGROUND: Posterior cruciate ligament reconstructions fail for similar reasons
      as to why anterior cruciate ligament reconstructions fail. Revision surgery is an
      option after failure. PURPOSE: To prospectively study the results of 15 posterior
      cruciate ligament revision surgeries using a 2-strand quadriceps tendon-patellar
      bone autograft. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The
      authors observed 15 knees that received the revision procedure a mean of 44
      months (range, 23-84 months) postoperatively. The results were determined by a
      comprehensive knee examination including stress radiography and several grading
      scales. A tibial inlay technique was used in 9 knees, and an arthroscopic tibial
      tunnel technique was done in 6 knees. Six knees required 1 or more concomitant
      ligament reconstructions. RESULTS: Significant improvements occurred in pain,
      function, and patient perception scores (P < .05). However, only 53% returned to
      light sports without problems. Stress radiograph posterior tibial translation
      values improved from 11.7 +/- 3.0 mm pre-operatively to 5.1 +/- 2.4 mm at follow
      up (P < .001). Two of the 15 revisions failed. Associated knee ligament
      reconstructive procedures restored anterior, medial, and posterolateral
      stability. There were no complications from the quadriceps tendon graft harvest
      site. Abnormal articular cartilage surfaces were found during the revision in 8
      (53%) knees. CONCLUSIONS: The quadriceps tendon 2-strand revision provided
      reasonable results in this group of complex-injured knees. The tibial inlay
      approach is advantageous to bypass prior tibial tunnels, and the all-inside
      arthroscopic technique is advantageous when major concurrent ligament
      reconstructions are required.

PMID- 15722279
TI  - Prevalence of jumper's knee among elite athletes from different sports: a cross
      sectional study.
AB  - BACKGROUND: The prevalence of jumper's knee across different sports has not been
      examined, and it is not known if there is a gender difference. Data from surgical
      case series indicate that there may be a high prevalence in sports with high
      speed and power demands. HYPOTHESIS: The aim of this study was to estimate the
      prevalence of jumper's knee in different sports among female and male athletes
      and to correlate the prevalence to the loading characteristics of the extensor
      mechanism in these sports. STUDY DESIGN: Cross-sectional study; Level of
      evidence, 4. METHODS: The authors examined approximately 50 Norwegian male and
      female athletes at the national elite level from each of the following 9 sports:
      athletics (male athletes: high jump, 100- and 200-m sprint), basketball (male
      athletes), ice hockey (male athletes), volleyball (male athletes), orienteering
      (male athletes), road cycling (male athletes), soccer (male and female athletes),
      team handball (male and female athletes), and wrestling (male athletes). The
      examination included an interview on individual characteristics (weight, age,
      height, and training background), a clinical examination, and self-recorded
      Victorian Institute of Sport Assessment score from 0 (worst) to 100 (best).
      RESULTS: The overall prevalence of current jumper's knee was 14.2% (87 of 613
      athletes), with a significant difference between sports with different
      performance characteristics (range, 0%-45%). In addition, 51 athletes (8%)
      reported previous symptoms. The prevalence of current symptoms was highest in
      volleyball (44.6%+/-6.6%) and basketball (31.9%+/-6.8%), whereas there were no
      cases in cycling or orienteering. The prevalence of current jumper's knee was
      lower among women (5.6%+/-2.2%) compared with men (13.5%+/-3.0%; chi2 test,
      P=.042). The duration of symptoms among athletes with current jumper's knee
      (n=87) was 32+/-25 (standard deviation) months, with a Victorian Institute of
      Sport Assessment score of 64+/-19. CONCLUSION: The prevalence of jumper's knee is
      high in sports characterized by high demands on speed and power for the leg
      extensors. The symptoms are often serious, resulting in long-standing impairment
      of athletic performance.

PMID- 15722280
TI  - Comparison of dynamic sonography to stress radiography for assessing glenohumeral
      laxity in asymptomatic shoulders.
AB  - BACKGROUND: Stress radiography has been the established imaging method for
      quantifying glenohumeral joint laxity. Dynamic ultrasound is an alternative
      imaging method that may be used to measure glenohumeral laxity; however, validity
      and repeatability have not been examined. OBJECTIVE: To determine criterion
      related validity and repeatability of a sonographic imaging method for measuring
      glenohumeral laxity in asymptomatic shoulders. STUDY DESIGN: Controlled
      laboratory study. METHODS: In experiment 1, 20 subjects were assessed for
      glenohumeral laxity using stress radiography and dynamic ultrasound. In the
      second experiment, 13 subjects were assessed for laxity in 2 separate test
      sessions using the dynamic ultrasound technique. RESULTS: Correlational analysis
      between the sonographic and radiographic measures revealed an r = 0.79 (r(2) =
      0.62), indicating excellent criterion-related validity for the sonographic
      imaging method. Test-retest repeatability was 0.72 and 0.85 for anterior and
      posterior translation, respectively, and interrater repeatability was 0.96 and
      0.99 for anterior and posterior translation, respectively. CONCLUSIONS: Dynamic
      ultrasound appears to be a valid and repeatable method for assessing glenohumeral
      laxity in a clinical setting. CLINICAL RELEVANCE: Based on the results of this
      study, dynamic ultrasound is a repeatable and valid method for measuring
      glenohumeral laxity and therefore may be used as a viable replacement for stress
      radiography during assessments of glenohumeral laxity.

PMID- 15722281
TI  - Compaction of a bone dowel in the tibial tunnel improves the fixation stiffness
      of a soft tissue anterior cruciate ligament graft: an in vitro study in calf
      tibia.
AB  - BACKGROUND: Despite increasing attention on fixation of a soft tissue anterior
      cruciate ligament graft in the tibia, there have been no studies on the use of a
      bone dowel as a joint line fixation device for promoting fixation properties,
      especially stiffness at the time of implantation. PURPOSE: To determine whether
      compacting a bone dowel into the tibial tunnel improves fixation stiffness, yield
      load, and resistance to slippage of a soft tissue anterior cruciate ligament
      graft. STUDY DESIGN: Controlled laboratory study. METHODS: A double-looped tendon
      graft was fixed at the distal end of the tibial tunnel with a WasherLoc in 24
      calf tibias. The tibial tunnels were treated with or without a dowel of
      cancellous bone. The bone dowel was harvested from the tibial tunnel and then
      compacted into a tapered space anterior to the anterior cruciate ligament graft
      as a joint line fixation device. A cyclic load and measurement test was
      administered to determine fixation stiffness, yield load, slippage, and failure
      mode. RESULTS: The specimens with the bone dowel had 58 N/mm more stiffness (P =
      .04); however, the yield load and resistance to slippage were similar in
      specimens with and without the bone dowel. CONCLUSIONS: A bone dowel harvested
      from the tibial tunnel can be used as a joint line fixation device in series with
      a distal fixation method to improve initial fixation stiffness and increase the
      fit, which is known to enhance tendon graft-to-bone healing in the tibia.

PMID- 15722282
TI  - The remains of anterior cruciate ligament graft tension after cyclic knee motion.
AB  - BACKGROUND: There is sometimes a return of excess knee laxity after anterior
      cruciate ligament reconstruction. One of the contributing factors might be a loss
      in graft tension. It is unknown whether the tension imposed on an anterior
      cruciate ligament graft degrades with time and, if so, the effect of that loss of
      tension on knee laxity. HYPOTHESES: The pretension in the anterior cruciate
      ligament graft reduces significantly within the first 500 motion cycles, and this
      decrease in graft tension causes an increase in knee laxity. STUDY DESIGN:
      Controlled laboratory study. METHODS: This study measured the remains of bone
      patellar tendon-bone graft pretension after cyclical flexion-extension and the
      effect of any tension loss on knee laxity, using 8 cadaveric knees. A tension
      transducer was inserted into the graft and calibrated in situ. The reconstruction
      tension was 40 N at 20 degrees of flexion. In test 1, the graft tension was
      measured under cyclical flexion-extension in a motorized rig up to 1500 cycles.
      Test 2, with a new graft, also included anteroposterior and internal-external
      rotational knee laxity measurements at 0, 500, and 1500 cycles. RESULTS: The
      graft tension at 0 degrees of flexion dropped from 208 N, by 25% after 50 cycles,
      41% by 500, and 46% by 1500 cycles. Anterior laxity increased from +1.4 to +2.8
      mm by 500 cycles, and performing these laxity tests also caused significant
      tension losses. CLINICAL RELEVANCE: These results provide one possible
      explanation for early slackening of anterior cruciate ligament reconstructions.

PMID- 15722283
TI  - Anterior cruciate ligament injury in national collegiate athletic association
      basketball and soccer: a 13-year review.
AB  - BACKGROUND: Female collegiate athletes have been reported to have a higher rate
      of anterior cruciate ligament injury compared to male collegiate athletes. This
      finding has spawned a branch of research focused on understanding and preventing
      this injury pattern. PURPOSE: To determine if the trends reported in 1994 have
      continued. STUDY TYPE: Descriptive epidemiology study. METHODS: The National
      Collegiate Athletic Association Injury Surveillance System database was reviewed
      for all data relating to men's and women's basketball and soccer anterior
      cruciate ligament injuries for 1990 to 2002. RESULTS: No significant difference
      was seen in basketball comparing frequency of contact versus noncontact injuries
      between men (70.1%) and women (75.7%). Male basketball players sustained 37
      contact injuries and 78 noncontact injuries. Female basketball players sustained
      100 contact injuries and 305 noncontact injuries. In soccer, there was a
      significant difference in frequency of injury for male (49.6%) and female (58.3%)
      athletes when comparing contact and noncontact injuries (chi2=4.1, P<.05). Male
      soccer players sustained 72 contact injuries and 66 noncontact injuries. Female
      soccer players sustained 115 contact injuries and 161 noncontact injuries. The
      magnitude of the difference in injury rates between male and female basketball
      players (0.32-0.21, P=.93) remained constant, whereas the magnitude of the
      difference in the rate of injuries between male and female soccer players (0.16
      0.21, P=.08) widened. Comparing injury within gender by sport, soccer players
      consistently sustained more anterior cruciate ligament injuries than did
      basketball players. The rate of anterior cruciate ligament injury for male soccer
      players was 0.11 compared to 0.08 for male basketball players (P=.002). The rate
      of anterior cruciate ligament injury for female soccer players was 0.33 and for
      female basketball players was 0.29 (P=.04). The rates for all anterior cruciate
      ligament injuries for women were statistically significantly higher (P<.01) than
      the rates for all anterior cruciate ligament injuries for men, regardless of the
      sport. In soccer, the rate of all anterior cruciate ligament injuries across the
      13 years for male soccer players significantly decreased (P=.02), whereas it
      remained constant for female players. CONCLUSIONS: In this sample, the rate of
      anterior cruciate ligament injury, regardless of mechanism of injury, continues
      to be significantly higher for female collegiate athletes than for male
      collegiate athletes in both soccer and basketball. CLINICAL RELEVANCE: Despite
      vast attention to the discrepancy between anterior cruciate ligament injury rates
      between men and women, these differences continue to exist in collegiate
      basketball and soccer players. Also demonstrated is that although the rate of
      injury for women is higher than for men, the actual rate of injury remains low
      and should not be a deterrent to participation in sports.

PMID- 15722284
TI  - Rotational motion changes in the glenohumeral joint of the adolescent/Little
      League baseball player.
AB  - BACKGROUND: Differences in range of motion and rotational motion between the
      dominant and nondominant shoulders in throwing athletes are well documented,
      although the age at which these changes begin to occur is not known. HYPOTHESIS:
      Changes in glenohumeral rotational motion in the shoulder of the Little
      League/adolescent baseball player occur during the most formative years of
      physical development. STUDY DESIGN: Cross-sectional study. METHODS: Elevation,
      internal rotation at 90 degrees of abduction, and external rotation at 90 degrees
      of abduction were measured in the dominant and nondominant shoulders of 294
      baseball players, aged 8 to 16 years. RESULTS: Analysis of variance revealed 2
      way interactions between arm dominance by age for elevation (P = .005) and
      internal rotation (P = .001). Significant differences were noted between dominant
      and nondominant arms for internal rotation at 90 degrees (P = .001) and external
      rotation at 90 degrees (P = .001). Elevation, internal rotation at 90 degrees ,
      external rotation at 90 degrees , and total range of motion varied significantly
      (P = .001) among age groups. Elevation in the dominant arms of 16-year-olds was
      on average 5.3 degrees less than in 8-year-olds (179.6 degrees vs 174.3 degrees
      ). In the nondominant arms, mean elevation for 16-year-olds was 5.6 degrees less
      than in 8-year-olds (179.7 degrees vs 174.1 degrees ). Internal rotation at 90
      degrees for the dominant arms averaged 39.0 degrees at age 8 and only 21.3
      degrees at age 16. In the non-dominant arms, internal rotation for 8-year-olds
      averaged 42.2 degrees and only 33.1 degrees for 16-year-olds. CONCLUSIONS:
      Elevation and total range of motion decreased as age increased. These changes may
      be consequences of both bone and soft tissue adaptation. The most dramatic
      decline in total range of motion was seen between the 13-year-olds and 14-year
      olds, in the year before peak incidence of Little Leaguer's shoulder. This
      decrease in rotational motion may cause increased stress at the physis during
      throwing.

PMID- 15722285
TI  - Reliability of stress radiography for evaluation of posterior knee laxity.
AB  - BACKGROUND: Although stress radiography has been recommended for quantifying
      posterior tibial displacement in knees with posterior cruciate ligament
      insufficiency, the intratester reliability and intertester reliability of this
      measurement method have not been evaluated. HYPOTHESIS: Stress radiography is a
      reproducible measurement method in the assessment of posterior knee laxity in
      patients with posterior cruciate ligament lesions. STUDY DESIGN: Cohort study
      (diagnosis); Level of evidence, 2. METHODS: Stress radiographs of 787 patients
      with suspected posterior cruciate ligament lesions taken using the Telos device
      were evaluated independently by 3 testers: 2 of the testers were clinically
      experienced in the evaluation of stress radiographs, and 1 tester was a novice
      tester. Change in mean, standard error of measurement with calculated confidence
      intervals, and intra-class correlation coefficients were determined to assess
      intratester and intertester reliability. RESULTS: There was no significant
      intratester change in mean. Intratester standard error of measurement was 1.03
      mm; 95% confidence intervals were+/-2.02 mm for a single measurement and+/-2.86
      mm for a change in measurement. The intratester intra-class correlation
      coefficient was 0.95. Intertester reliability revealed a significant change in
      mean between the experienced testers and the novice tester (P<.001). There was no
      substantial difference for the standard error of measurement of each tester. The
      mean intertester standard error of measurement was 1.41 mm; 95% confidence
      intervals were+/-2.77 mm for a single measurement and+/-3.91 mm for a change in
      measurement. The intertester intraclass correlation coefficient was 0.91.
      CONCLUSION: Stress radiography was found to be a measurement method with a useful
      reliability for evaluation of posterior laxity in patients with posterior
      cruciate ligament lesions. The reproducibility of stress radiography may be
      influenced by multiple variables, and standardized methods are needed to minimize
      measurement error.

PMID- 15722286
TI  - The effect of analgesic agents on the healing rat medial collateral ligament.
AB  - BACKGROUND: Studies have suggested that some nonselective nonsteroidal anti
      inflammatory drugs, including piroxicam, may improve ligament healing, whereas
      other nonsteroidal anti-inflammatory drugs, including ibuprofen and the
      cyclooxygenase-2 inhibitor celecoxib, may have no effect on the mechanical
      properties or may even deter the healing process. These results might reflect
      variations in cyclooxygenase enzyme selectivity by different drugs or,
      alternatively, may be related to their analgesic properties because it is
      generally accepted that early activity improves ligament healing. HYPOTHESIS:
      Nonselective nonsteroidal anti-inflammatory drugs improve ligament healing,
      whereas other analgesics provide lesser degrees of improvement, and
      cyclooxygenase-2 inhibitors are detrimental. STUDY DESIGN: Controlled laboratory
      study. METHODS: One hundred fifty-five Sprague-Dawley rats were divided into 7
      treatment groups (piroxicam, naproxen, rofecoxib, butorphanol, 2 doses of
      acetaminophen, and control). The right medial collateral ligament of each rat was
      transected, and the drugs were administered postoperatively on days 1 to 6. On
      day 14, the rats were sacrificed, and mechanical testing was performed on the
      medial collateral ligament. RESULTS: The piroxicam group demonstrated
      significantly greater load to failure (27%) compared with the control. No
      significant differences were observed between other groups. CONCLUSIONS:
      Piroxicam improves ligament healing, but this effect cannot be attributed to all
      nonselective nonsteroidal anti-inflammatory drugs. Opiate analgesics,
      acetaminophen, and cyclooxygenase-2 inhibitors do not appear to categorically
      affect ligament healing. CLINICAL RELEVANCE: In the treatment of ligament injury,
      piroxicam may be a drug of choice.

PMID- 15722287
TI  - Biomechanical measures of neuromuscular control and valgus loading of the knee
      predict anterior cruciate ligament injury risk in female athletes: a prospective
      study.
AB  - BACKGROUND: Female athletes participating in high-risk sports suffer anterior
      cruciate ligament injury at a 4- to 6-fold greater rate than do male athletes.
      HYPOTHESIS: Prescreened female athletes with subsequent anterior cruciate
      ligament injury will demonstrate decreased neuromuscular control and increased
      valgus joint loading, predicting anterior cruciate ligament injury risk. STUDY
      DESIGN: Cohort study; Level of evidence, 2. METHODS: There were 205 female
      athletes in the high-risk sports of soccer, basketball, and volleyball
      prospectively measured for neuromuscular control using 3-dimensional kinematics
      (joint angles) and joint loads using kinetics (joint moments) during a jump
      landing task. Analysis of variance as well as linear and logistic regression were
      used to isolate predictors of risk in athletes who subsequently ruptured the
      anterior cruciate ligament. RESULTS: Nine athletes had a confirmed anterior
      cruciate ligament rupture; these 9 had significantly different knee posture and
      loading compared to the 196 who did not have anterior cruciate ligament rupture.
      Knee abduction angle (P<.05) at landing was 8 degrees greater in anterior
      cruciate ligament-injured than in uninjured athletes. Anterior cruciate ligament
      injured athletes had a 2.5 times greater knee abduction moment (P<.001) and 20%
      higher ground reaction force (P<.05), whereas stance time was 16% shorter; hence,
      increased motion, force, and moments occurred more quickly. Knee abduction moment
      predicted anterior cruciate ligament injury status with 73% specificity and 78%
      sensitivity; dynamic valgus measures showed a predictive r2 of 0.88. CONCLUSION:
      Knee motion and knee loading during a landing task are predictors of anterior
      cruciate ligament injury risk in female athletes. CLINICAL RELEVANCE: Female
      athletes with increased dynamic valgus and high abduction loads are at increased
      risk of anterior cruciate ligament injury. The methods developed may be used to
      monitor neuromuscular control of the knee joint and may help develop simpler
      measures of neuromuscular control that can be used to direct female athletes to
      more effective, targeted interventions.

PMID- 15722288
TI  - Pediatric fractures during skateboarding, roller skating, and scooter riding.
AB  - BACKGROUND: Skateboarding, roller skating, and scooter riding are popular
      recreational and sporting activities for children and adolescents but can be
      associated with skeletal injury. The purpose of this study is to describe the
      frequency and characteristics of fractures resulting from these activities.
      PURPOSE: Fractures from skateboarding, roller skating, and scooter riding compose
      a considerable proportion of pediatric musculoskeletal injuries. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: Demographic data and injury
      characteristics were analyzed for all patients who presented to the pediatric
      fracture clinic of the level I trauma center from January 2001 to May 2002 after
      sustaining fractures due to skateboarding, roller skating, and scooter riding.
      RESULTS: Among a total of 2371 fractures, the authors identified 325 fractures
      (13.7%) that occurred during one of these activities. There were 187 patients
      (mean age, 13 years; 95% male) who sustained 191 skateboard-related fractures, 64
      patients (mean age, 10.8 years; 54% male) who sustained 65 fractures while roller
      skating, and 66 patients (mean age, 9.7 years; 64% male) who sustained 69
      fractures while riding a scooter. The forearm was fractured most often, composing
      48.2% of skate-boarding fractures, 63.1% of roller-skating fractures, and 50.7%
      of fractures due to scooter riding. Of the forearm fractures, 94% were located in
      the distal third. In the skateboarding group, 10 of 191 (5.2%) fractures were
      open injuries of the forearm, compared to 6 of 2046 (0.3%) fractures caused by
      other mechanisms of injury (significant odds ratio, 18.8). CONCLUSIONS:
      Skateboarding, roller-skating, and scooter-riding accidents result in a large
      proportion of pediatric fractures. An open fracture, especially of the forearm,
      was more likely to be caused by skateboarding than by other mechanisms of injury.
      Use of wrist and forearm protective equipment should be considered in all
      children who ride a skateboard.

PMID- 15722289
TI  - Sports activity after arthroscopic superior labral repair using suture anchors in
      overhead-throwing athletes.
AB  - PURPOSE: To evaluate the results of arthroscopic repair of type II superior
      labral anterior posterior lesions of the shoulder in overhead athletes.
      HYPOTHESIS: Such repair is useful for overhead athletes in terms of postoperative
      sports activity. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The
      study group was composed of 40 patients with a mean age of 24 years (range, 15-38
      years); mean follow-up was 41 months (range, 24-58 months). They were divided
      into an overuse (n=22) and a trauma group (n=18). The authors used 2 suture
      anchors loaded with a nonabsorbable suture at the 11-o'clock and 1-o'clock
      positions through the anterosuperior and lateral trans-rotator cuff portal. A
      modified Rowe score and postoperative athletic activities were evaluated.
      RESULTS: After arthroscopic repair, mean modified Rowe scores improved from 27.5
      to 92.1 points (P<.0001). Rated on this scale, the results were excellent in 30
      (75%), good in 6 (15%), and fair in 4 (10%) athletes; there were no poor results.
      Satisfactory outcomes were achieved in 36 (90%) of these patients; 30 (75%)
      experienced a return to the preinjury level. The complete return rate of baseball
      players in the overuse group was lower than that of other overhead athletes in
      the trauma group. CONCLUSION: Arthroscopic superior labral repair is a safe and
      reliable procedure in overhead athletes.

PMID- 15722290
TI  - Extensive osteolysis after rotator cuff repair with a bioabsorbable suture
      anchor: a case report.

PMID- 15722291
TI  - Biomechanics of youth windmill softball pitching.
AB  - BACKGROUND: Limited research attention has been paid to the potentially harmful
      windmill softball pitch. No information is available regarding lower extremity
      kinetics in softball pitching. HYPOTHESIS: The stresses on the throwing arm of
      youth windmill pitchers are clinically significant and similar to those found for
      college softball pitchers. STUDY DESIGN: Descriptive laboratory study. METHODS:
      Three-dimensional, high-speed (240-Hz) video and stride foot force plate (1200
      Hz) data were collected on fastballs from 53 youth softball pitchers. Kinematic
      parameters related to pitching mechanics and resultant kinetics on the throwing
      arm elbow and shoulder joints were calculated. Kinetic parameters were compared
      to those reported for baseball pitchers. RESULTS: Elbow and shoulder joint loads
      were similar to those found for baseball pitchers and college softball pitchers.
      Shoulder distraction stress averaged 94% body weight for the youth pitchers.
      Stride foot ground reaction force patterns were not similar to those reported for
      baseball pitchers. Vertical and braking force components under the stride foot
      were in excess of body weight. CONCLUSIONS: Excessive distraction stress and
      joint torques at the throwing-arm elbow and shoulder are similar to those found
      in baseball pitchers, which suggests that windmill softball pitchers are at risk
      for overuse injuries. Normative information regarding upper and lower extremity
      kinematics and kinetics for 12- to 19-year-old softball pitchers has been
      established.

PMID- 15722292
TI  - Athletes with unilateral spondylolysis are at risk of stress fracture at the
      contralateral pedicle and pars interarticularis: a clinical and biomechanical
      study.
AB  - BACKGROUND: Unilateral spondylolysis is common in youths; its clinical and
      biomechanical features, especially effects on the contralateral side, are not
      fully understood. HYPOTHESIS: Unilateral spondylolysis predisposes the
      contralateral side to stress fracture, especially in athletes actively engaged in
      sporting activities involving torsion of the trunk. STUDY DESIGN: Case series and
      descriptive laboratory study. METHODS: Thirteen athletes younger than age 20 with
      unilateral spondylolysis were included. The contralateral pedicle and pars of
      spondylolytic vertebrae were examined using computed tomography and magnetic
      resonance imaging. Using a finite element model of the intact ligamentous L3-S1
      segment, stress distributions were analyzed in response to 400-N axial
      compression and 10.6-N.m moment in flexion, extension, lateral bending, and axial
      rotation. Unilateral spondylolysis was created in the model at L5. The stress
      results from the unilateral defect model were compared to the intact model
      predictions and correlated to the contralateral defects seen in patients.
      RESULTS: Among 13 patients, there were 6 early-, 2 progressive-, and 5 terminal
      stage defects. Three (23.1%) showed contralateral stress fracture. Among them, 2
      belonged to the progressive-stage and 1 to the terminal-stage spondylolysis
      group. The remaining 4 patients in the terminal defect group showed stress
      reactions, such as sclerosis at the contralateral pedicle. In the finite element
      analysis model with an L5 left spondylolysis, the stresses at the contralateral
      and pars interarticularis were found to increase in all loading modes, with
      increases as high as 12.6-fold compared to the intact spine. CONCLUSIONS:
      Unilateral spondylolysis could lead to stress fracture or sclerosis at the
      contralateral side due to an increase in stresses in the region. CLINICAL
      RELEVANCE: Surgeons should be aware of possibility of contralateral stress
      fractures in cases in which patients, especially athletes engaged in active
      sports, show unilateral spondylolysis and persistent low back pain complaints.

PMID- 15722293
TI  - Rotator cuff tears in adolescent athletes.

PMID- 15722294
TI  - Neuromuscular response to cyclic loading of the anterior cruciate ligament.
AB  - BACKGROUND: Cyclic load applied to various joints during occupational and sports
      activities is epidemiologically linked to higher risk of neuromuscular disorder
      development. HYPOTHESIS: Passive cyclic loading of the knee will develop laxity
      and creep in the anterior cruciate ligament, and these may elicit a neuromuscular
      disorder in the quadriceps and hamstrings. Women may be more susceptible to the
      disorder. STUDY DESIGN: Controlled laboratory study. METHODS: Male and female
      groups were subjected to 10 minutes of passive cyclic loading (0.1 Hz) of the
      knee at a mild load (150-200 N) and at 35 degrees and 90 degrees flexion.
      Anterior tibial displacement and electromyogram from the quadriceps and
      hamstrings were monitored during cyclic loading. Maximal voluntary contraction of
      knee extension and flexion was assessed before and after cyclic loading. The
      effect of gender and angle on maximal voluntary contraction and
      quadriceps/hamstrings electromyogram was tested by a 2-way analysis of variance.
      Differences between the preload and postload data were tested by a paired t test.
      RESULTS: At a knee angle of 90 degrees, after cyclic loading, a decrease in
      maximal voluntary contraction during extension was present in men and women, with
      an associated decrease in quadriceps electromyogram activity. At 35 degrees, a
      decrease in maximal voluntary contraction in extension was noted in women and
      men. Electromyogram spasms were present in the quadriceps and hamstrings during
      the 10-minute cyclic loading in 51.7% of subjects. Analysis of variance
      demonstrated that ligament creep was significantly greater in women than in men
      at both knee angles. CONCLUSIONS: Even a mild cyclic loading of the anterior
      cruciate ligament, for a relatively short period, can elicit substantial creep,
      laxity, and a neuromuscular disorder. The disorder is composed of spasms and
      attenuated muscular function that may together create a condition that exposes
      the knee to injury. Women seem to be more susceptible than men. CLINICAL
      RELEVANCE: Cyclic actions performed at high frequencies and high-load magnitudes
      may lead to the occurrence of increased knee laxity and changes in neuromuscular
      function that, together with fatigue and changes in proprioception, may increase
      the risk of injury.

PMID- 15722295
TI  - Topical ketoprofen patch (100 mg) for the treatment of ankle sprain: a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Topical nonsteroidal anti-inflammatory drugs offer the advantage of
      enhanced drug delivery to local affected tissues with low plasma levels and an
      expected reduced incidence of systemic adverse events (mainly peptic ulcer
      disease and gastrointestinal hemorrhage). HYPOTHESIS: To test the efficacy and
      tolerability of a 100-mg patch of ketoprofen applied once a day. STUDY DESIGN:
      Randomized controlled clinical trial; Level of evidence, 1. METHODS: The 2-week
      trial included patients suffering painful (spontaneous pain >or=50 mm on a 0- to
      100-mm visual analog scale), benign (grade I or II), recent (<2 days) ankle
      sprains as a model of general traumatic soft tissue injuries. The primary
      efficacy criterion was spontaneous pain change after 7 days of treatment in the
      intention-to-treat population. One hundred sixty-three patients were randomized
      (ketoprofen, 81; placebo, 82). RESULTS: After 1 week of treatment, the decrease
      in spontaneous pain was -50+/-20 mm for ketoprofen and -38+/-24 mm for the
      placebo, showing a statistically significant intergroup difference (P=.0007). The
      majority of the secondary criteria were also statistically significant in favor
      of the ketoprofen patch. Tolerance was good in both groups, adverse events being
      mostly local. CONCLUSION: This trial suggested that a 7-day course of treatment
      with a ketoprofen patch is useful in benign ankle sprain, without revealing
      unexpected adverse events.

PMID- 15722296
TI  - Evidence about evidence.

PMID- 15722297
TI  - Prevention of diabetic keratopathy.

PMID- 15722298
TI  - Current estimates of blindness in India.
AB  - BACKGROUND: Evidence based planning has been the hallmark of the blindness
      control programme in India. A nationwide survey was undertaken in 1999-2001 to
      document the magnitude and causes of blindness. METHODS: One district each in 15
      populous states was covered. 25 clusters were randomly selected in each district
      and all individuals aged 50 years and above were enumerated. Presenting and best
      corrected vision was recorded using retroilluminated logMAR tumbling E charts and
      detailed eye examination was offered. RESULTS: The response rate was 89.3%.
      Presenting vision <6/60, in the better eye, was observed in 8.5% (95% CI: 8.1 to
      8.9). Age, sex, residence, literacy, and working status were associated with
      blindness. The highest risk was among those aged 70+ and the illiterate. Cataract
      was responsible for 62.4% of bilateral blindness. Prevalence of cataract
      blindness was 5.3% (95% CI: 4.97 to 5.62). Reduction in blindness prevalence
      among people aged 50 years and above was observed compared to earlier studies.
      CONCLUSION: Blindness control efforts seem to have played a part in arresting the
      increasing prevalence of blindness in India and there is hope that the goals of
      the "Vision 2020--right to sight" initiative can be achieved if there is strong
      political will and prioritised action.

PMID- 15722299
TI  - The quality of reporting of diagnostic accuracy studies published in ophthalmic
      journals.
AB  - AIM: To evaluate the quality of reporting of all diagnostic studies published in
      five major ophthalmic journals in the year 2002 using the Standards for Reporting
      of Diagnostic Accuracy (STARD) initiative parameters. METHODS: Manual searching
      was used to identify diagnostic studies published in 2002 in five leading
      ophthalmic journals, the American Journal of Ophthalmology (AJO), Archives of
      Ophthalmology (Archives), British Journal of Ophthalmology (BJO), Investigative
      Ophthalmology and Visual Science (IOVS), and Ophthalmology. The STARD checklist
      of 25 items and flow chart was used to evaluate the quality of each publication.
      RESULTS: A total of 16 publications were included (AJO = 5, Archives = 1, BJO =
      2, IOVS = 2, and Ophthalmology = 6). More than half of the studies (n = 9) were
      related to glaucoma diagnosis. Other specialties included retina (n = 4) cornea
      (n = 2), and neuro-ophthalmology (n = 1). The most common description of
      diagnostic accuracy was sensitivity and specificity values, published in 13
      articles. The number of fully reported items in evaluated studies ranged from
      eight to 19. Seven studies reported more than 50% of the STARD items.
      CONCLUSIONS: The current standards of reporting of diagnostic accuracy tests are
      highly variable. The STARD initiative may be a useful tool for appraising the
      strengths and weaknesses of diagnostic accuracy studies.

PMID- 15722300
TI  - A randomised, placebo controlled clinical trial of the aldose reductase inhibitor
      CT-112 as management of corneal epithelial disorders in diabetic patients.
AB  - AIM: To evaluate the efficacy of topical aldose reductase inhibitor CT-112 (5-[3
      ethoxy-4-pentyloxyphenyl]-2,4-thiazolidinedione) on corneal epithelial barrier
      function in diabetic patients. METHODS: This was a prospective, randomised,
      double masked placebo controlled study. 34 eyes of 34 diabetic patients were
      randomly assigned treatment with 0.25% eye drops of CT-112 (n = 22) or a placebo
      (n = 12) four times a day for 8 weeks. Corneal fluorescein staining and corneal
      sensation were examined before treatment as well as 4 and 8 weeks after
      administration. Corneal epithelial permeability to fluorescence was measured with
      an anterior fluorophotometer. RESULTS: Average scores of superficial punctate
      keratopathy and corneal sensitivity did not differ significantly between the two
      groups at any time. Whereas average fluorescein concentrations did not differ
      significantly for the CT-112 and placebo groups before treatment, they did differ
      significantly 4 and 8 weeks after treatment (4 weeks, p = 0.0327; 8 weeks, p =
      0.0143). CONCLUSION: The topical aldose reductase inhibitor, CT-112 improves the
      corneal epithelial barrier function in diabetic patients.

PMID- 15722301
TI  - Characterisation of myofibroblasts in fibrovascular tissues of primary and
      recurrent pterygia.
AB  - AIMS: To determine the presence and origin of myofibroblasts in pterygia.
      METHODS: 86 specimens including head, body, and fibrovascular tissue from 52
      primary and 34 recurrent pterygia and five exenterated eyes without pterygia were
      searched for the origin of myofibroblasts. All tissues were subjected to
      haematoxylin and eosin staining, immunohistochemistry using antibodies against
      alpha smooth muscle actin (alpha-SMA), desmin, vimentin, and caldesmon, and
      transmission electron microscopy (TEM). The phenotype of fibroblasts subcultured
      in a serum free medium from pterygium fibrovascular tissues was characterised by
      the above antibodies. Bundles of dense fibrous tissues were noted in 86% of the
      fibrovascular tissue specimens evaluated. Cells within these bundles were
      characterised as myofibroblasts based on positive staining to alpha-SMA, but
      negative to desmin and caldesmon, markers for smooth muscle cells. Interestingly,
      positive alpha-SMA staining was also found in the periorbital fibroadipose tissue
      posterior to Tenon's capsule near the nasal conjunctiva in all exenterated
      specimens. All first passage fibroblasts expressed vimentin, some were positive
      to alpha-SMA, but all were negative to desmin or caldesmon. Cells in pterygium
      fibrovascular tissues showed ultrastructural features of intracytoplasmic bundles
      of microfilaments, consistent with myofibroblastic differentiation. CONCLUSION:
      These studies collectively demonstrate the presence of contractile myofibroblasts
      bundle in pterygia and in the periorbital fibroadipose tissue posterior to
      Tenon's capsule of exenterated eyes without pterygium.

PMID- 15722302
TI  - The effects of atorvastatin in experimental autoimmune uveitis.
AB  - AIM: To investigate the effect of atorvastatin (Lipitor), a commonly used drug
      for dyslipidaemia in experimental autoimmune uveitis (EAU). METHODS: 48 B10-RIII
      mice were immunised with human interphotoreceptor retinoid binding protein (IRBP)
      peptide p161-180. They were divided into three groups of 16 each and treated
      orally once daily for 14 days; group one received phosphate buffered saline
      (control group), group two received 1 mg/kg of atorvastatin (low dose group), and
      group three received 10 mg/kg (high dose). On day 14 lymph nodes, spleens, and
      right eyes were harvested. RNA was extracted from lymph nodes for RNase
      protection assay (RPA) to determine proinflammatory (IL-1 alpha and IL-1 beta),
      Th1 (TNF-alpha, IL-2, IL-12), and Th2 (IL-4, IL-5, and IL-10) cytokine levels.
      Protein was extracted from spleens for western blot to detect the expression of
      phosphorylated signal transducer and activator of transcription (STAT) 4 and
      STAT6. The severity of inflammation in enucleated eyes was graded by a masked
      observer. Paired t test was performed for the mean difference in histological
      scoring between treated groups and the immunised control group. RESULTS:
      Surprisingly, atorvastatin did not modulate the immune response. The
      proinflammatory cytokines, IL-1 alpha and IL-1 beta, and Th1 cytokines, TNF-alpha
      and IL-2, were upregulated equally in control and atorvastatin treated groups. IL
      12 and Th2 cytokines were not upregulated in all three groups. Western blot
      analysis showed high levels of phosphorylated STAT4, but not STAT6 protein in the
      control and atorvastatin treated groups. Mean differences in histological scoring
      between treated groups and the immunised control group were not statistically
      significant. CONCLUSIONS: Atorvastatin treatment had no effect on Th1 and Th2
      cytokine transcription. Although histological grading suggested mildly decreased
      inflammation in the high dose treated group, the equivalence of cytokine
      expression in all groups suggests that the statins may not modulate IRBP induced
      uveoretinitis.

PMID- 15722303
TI  - Transpalpebral tonometry: reliability and comparison with Goldmann applanation
      tonometry and palpation in healthy volunteers.
AB  - BACKGROUND/AIM: TGDc-01 is a new, portable, transpalpebral tonometry device. The
      aim of this study was to evaluate the reproducibility of this method, including
      intraobserver and interobserver deviations, and to compare the results with those
      of Goldmann applanation tonometry and palpation of intraocular pressure (IOP).
      METHODS: A total of 40 eyes of 20 healthy volunteers were included. Two
      independent parallel observers (1 and 2) performed three replicate measurements
      per eye, respectively, both using TGDc01 tonometry, one observer (3) performed
      three replicate measurements using Goldmann applanation tonometry, and one
      observer (4) measured the IOP via palpation. Intraindividual deviations within
      and between both observers using TGDc-01 tonometry and between all three methods
      were investigated about clinically relevance by comparison of medians and
      quartiles, statistically significance by pairwise sign tests. Comparisons between
      observers and methods were based on averaged IOP values of the three individual
      measurements for each observer and each patient. Intraobserver deviations were
      analysed by means of Friedman tests. RESULTS: Observers 1 and 2 showed a
      statistically significant intraobserver deviation when using TGCc-01 (Friedman p
      = 0.007 for observer 1 and p = 0.002 for observer 2). There was no statistically
      significant interobserver deviation between observers 1 and 2 (sign test p =
      0.200); however, in 45% of the eyes interobserver deviations were larger than
      plus or minus 3 mm Hg. The median intraindividual deviation between TGDc-01 and
      Goldmann (TGDc-01 minus Goldmann) was 0 mm Hg (interquartile range -1; 2 mm Hg;
      sign test p = 0.522); but deviations were larger than plus or minus 3 mm Hg for
      38% of the 40 eyes. Median intraindividual deviation between TGDc-01 and
      palpation (TGDc-01 minus palpation) was -2 mm Hg (interquartile range -4; 1 mm
      Hg; sign test p = 0.018), but deviations were larger than plus or minus 3 mmHg
      for 43% of eyes. Median intraindividual deviation between Goldmann and palpation
      (palpation minus Goldmann) was 2 mm Hg (interquartile range -2; 4 mm Hg; p =
      0.429), but deviations were larger than plus or minus 3 mm Hg in 48% of the eyes.
      CONCLUSION: Interobserver deviations using TGDc-01 tonometry and intraindividual
      deviations between TGDc-01 tonometry, Goldmann applanation tonometry, and
      palpation of IOP were found to be clinically relevant. Thus, according to our
      results TGDc-01 could not be established as a substitute or diagnostic
      alternative method for Goldmann applanation tonometry. But as deviations between
      TGDc01 and Goldmann turned out smaller than between palpation of IOP and
      Goldmann, TGDc-01 seems to provide a better choice for tonometry in patients, in
      whom Goldmann applanation tonometry is not possible.

PMID- 15722304
TI  - Intraocular pressure and systemic blood pressure: longitudinal perspective: the
      Beaver Dam Eye Study.
AB  - AIM: To investigate the relation between change in systemic blood pressures and
      change in intraocular pressure. METHODS: This was a population based study of
      people 43-86 years old living in Beaver Dam, Wisconsin. Measurements at baseline
      (1988-90) and 5 year follow up of systemic blood pressures, intraocular
      pressures, and history of use of blood pressure medications. RESULTS: Intraocular
      pressures were significantly correlated with systolic and diastolic blood
      pressures at both baseline and follow up. There were significant direct
      correlations between changes in systemic blood pressures and changes in
      intraocular pressure. There was a 0.21 (95% CI: 0.16 to 0.27) mm Hg increase in
      IOP for a 10 mm Hg increase in systolic and 0.43 (0.35 to 0.52) mm Hg increase in
      IOP for a 10 mm Hg increase in diastolic blood pressure. Further adjustment for
      diabetes and medication use did not alter these associations. Decreased systolic
      or diastolic blood pressures of more than 10 mm Hg over 5 years were
      significantly associated with decreased IOP. CONCLUSIONS: Reduced systemic blood
      pressure is associated with reduced intraocular pressure. This finding should be
      evaluated in other studies, especially with respect to the possibility of
      resultant decreased risk of open angle glaucoma.

PMID- 15722305
TI  - Choroidal expansion as a mechanism for acute primary angle closure: an
      investigation into the change of biometric parameters in the first 2 weeks.
AB  - BACKGROUND/AIM: Choroidal expansion with anterior movement of the lens was
      recently proposed as a mechanism for acute primary angle closure (APAC). The aim
      of this study was to compare the biometric parameters, central anterior chamber
      depth, limbal chamber depth, lens thickness, and lens position, within 24 hours
      of presentation and 2 weeks later in eyes with APAC. METHODS: This was a
      prospective observational case series of 41 subjects with APAC. Subjects who
      presented with APAC were treated with medical therapy followed by laser iridotomy
      (LI) in both eyes once the acute attack was broken. Ocular biometry was performed
      in affected and fellow eyes before LI (baseline) and then 2 weeks later. Optical
      pachymetry was used to measure central anterior chamber depth (ACD) and the
      limbal chamber depth (LCD) was graded at the slit lamp. A-scan ultrasound was
      used to measure lens thickness (LT) and axial length (AL). Lens position (LP) was
      defined as ACD +(1/2)LT. RESULTS: The majority of subjects were Chinese (83%) and
      female (61%), and the mean age was 60.4 (SD 10.3) years. In affected eyes, the
      ACD was 1.81 (0.29) mm before and 1.80 (0.28) mm 2 weeks after LI (p = 0.63),
      while in fellow eyes, the ACD was 1.83 (0.29) mm and 1.81 (0.38) mm, respectively
      (p = 0.21). There was no significant change in lens position, relative lens
      position, or axial length in both affected and fellow eyes over the 2 weeks.
      CONCLUSIONS: There was no change observed in central anterior chamber depth, lens
      thickness, or lens position at the time of the acute attack compared to 2 weeks
      later in both APAC affected and fellow eyes. The findings do not support the
      hypothesis of lens movement due to choroidal expansion in APAC.

PMID- 15722306
TI  - Randomised controlled trial of sub-Tenon's block versus topical anaesthesia for
      cataract surgery: a comparison of patient satisfaction.
AB  - BACKGROUND/AIM: Sub-Tenon's block (STB) or topical anaesthesia alone (TOP) are
      popular techniques employed during cataract surgery. TOP is often preferred by
      healthcare providers because of financial or staffing reasons, despite existing
      evidence that pain during surgery is better controlled with STB. Pain is not the
      only consideration that determines patient preference for the anaesthesia
      technique. The authors decided to investigate the issue of patient satisfaction
      using the recently developed Iowa Satisfaction with Anesthesia Scale (ISAS).
      METHOD: In a randomised controlled pilot trial, 28 patients were enrolled to
      receive either STB with 3 ml of 2% lidocaine and hyaluronidase, or TOP with
      proxymetacaine 0.5% and amethocaine 1% (Tetracaine) eye drops. Postoperatively
      patients rated their satisfaction with anaesthesia care by filling in the self
      administered written questionnaire, the ISAS. RESULTS: One patient in the TOP
      group dropped out of the study because of intolerable pain. Analysis of the
      questionnaire results with a two sample Wilcoxon rank sum test showed a
      significant difference in patient satisfaction (p<0.0085). The median
      satisfaction score was higher in the STB group 2.77 (interquartile range IQR 2.45
      to 3), than in the TOP group 2.04 (IQR 1.54 to 2.5). CONCLUSION: In the setting
      of day case cataract surgery, patients report significantly higher satisfaction
      scores with STB than with TOP alone.

PMID- 15722307
TI  - Optical coherence tomography of the retinal nerve fibre layer in mild
      papilloedema and pseudopapilloedema.
AB  - AIMS: To determine the degree to which optical coherence tomography (OCT) can
      distinguish differences in retinal nerve fibre layer (RNFL) thickness between
      eyes with mild papilloedema, pseudopapilloedema, and normal findings. METHODS: 13
      patients with mild papilloedema, 11 patients with congenitally crowded optic
      nerves, and 17 normal subjects underwent neuro-ophthalmic examination, automated
      visual field testing, and fundus photography. Spinal fluid pressure measurements
      were obtained in a subgroup of five patients with pseudopapilloedema and 11
      patients with mild papilloedema. Circular OCT scans using a diameter of 3.38 mm
      surrounding the optic disc were performed in each eye of patients and subjects.
      Fundus photographs were analysed by two observers who diagnosed crowding or
      papilloedema and graded amounts of swelling. Findings were assessed by
      descriptive statistics and variance analysis. RESULTS: RNFL thickness was greater
      in the superior and inferior quadrants and showed a high degree of correlation
      between each group of patients and subjects. A statistically significant
      difference was found in mean RNFL thickness between both groups of patients with
      optic disc swelling and normal subjects. However, there was not a statistical
      difference in mean nerve fibre layer thickness between patients with papilloedema
      and those with congenitally crowded optic nerves. CONCLUSIONS: OCT demonstrates
      measurable differences in nerve fibre layer thickness between normal subjects and
      patients with either papilloedema or pseudopapilloedema. However, OCT does not
      appear to differentiate between those individuals with congenitally crowded optic
      nerves and those with mild papilloedema caused by increased intracranial
      pressure.

PMID- 15722308
TI  - Relation of pre-LASIK and post-LASIK retinal lesions and retinal examination for
      LASIK eyes.
AB  - AIMS: Analysis of highly myopic eyes (mean myopia -11 D) with post-LASIK
      vitreoretinal complications (breaks, retinal detachment) that also had pre-LASIK
      vitreoretinal pathology (lattice, breaks). METHODS: Retrospective case series.
      RESULTS: 67 eyes in 56 patients with pre-LASIK retinal examination developed post
      LASIK vitreoretinal complications. 17 of the 67 eyes (25.4%) had pre-LASIK
      vitreoretinal pathology. 10 of the 17 eyes that underwent pre-LASIK prophylactic
      retinal treatment still developed post-LASIK lesions. They developed adjacent to
      pre-LASIK lesions for 15 of 17 eyes (88.2%), and outside of quadrant(s) of pre
      LASIK lesions for five eyes (29.4%). CONCLUSION: Pre-LASIK retinal examination
      may predict locations of certain post-LASIK retinal lesions that may develop in
      highly myopic eyes with pre-LASIK vitreoretinal pathology, but prophylactic
      treatment may not prevent all post-LASIK vitreoretinal complications.

PMID- 15722309
TI  - Case-controlled clinical and histopathological study of conjunctivochalasis.
AB  - BACKGROUND/AIMS: Conjunctivochalasis, a secondary cause of the watery eye, is
      frequently seen in the older age group as an elevation of the bulbar conjunctiva
      lying along the lateral or central lower lid margin. A prospective,
      interventional, case-controlled clinical and histopathological study was
      conducted. The relevant features of 18 patients (29 eyes) who had their
      conjunctivochalasis resected as part of the surgical management of their watery
      eye syndrome were examined. In the control group, tissue was obtained from an age
      matched series of 24 normal subjects undergoing routine cataract surgery.
      METHODS: 24 controls (24 specimens) and 18 patients (29 specimens) had
      conjunctival strip biopsies, taken from the usual lid margin level bulbar
      conjunctiva in line with the inferior limbus (controls), and the clinically
      apparent conjunctivochalasis (patients). These were submitted for histological
      study. RESULTS: 23 of 24 control sections demonstrated normal conjunctival
      variation. Four of 29 patient specimens demonstrated a chronic non-granulomatous
      conjunctivitis, while three eyes of the patient group (two patients) demonstrated
      features of elastosis. Of the four patients who had the inflammatory infiltrates,
      three had functional nasolacrimal duct obstructions (FNLDOs) and one had a
      primary acquired nasolacrimal duct obstruction (PANDO). Of the two patients who
      had elastosis, one had an FNLDO and the other had normal lacrimal drainage and
      was Jones 1 positive. CONCLUSION: Six of 18 patients--that is, seven of 29
      specimens of conjunctivochalasis demonstrated signs of elastosis or of chronic
      non-granulomatous inflammation. Clinically, patients had a spectrum of
      aetiologies of their watery eye syndrome.

PMID- 15722310
TI  - A new system for the automatic estimation of endothelial cell density in donor
      corneas.
AB  - AIMS: The problem of automatic estimation of endothelial cell density from
      microscopy images in donor corneas was addressed. METHODS: The spatial
      frequencies contained in digital endothelium images are extracted with a two
      dimension discrete Fourier transform (DFT) technique. A circular band in the DFT
      of the images is shown to contain the frequency information related to the cell
      density. An algorithm for reliably recovering this spatial frequency information
      and for extracting from it an estimate of endothelial cell density has been
      developed and implemented in a computer program. An evaluation was performed on a
      data set containing 100 donor corneas, by comparing automatic values with manual
      counts performed by three eye bank experts on two images for each cornea.
      RESULTS: The mean difference of automatic densities v manual ones was 14
      cells/mm(2) (0.9%), with a standard deviation of 119 cells/mm(2) (5.1%) and mean
      absolute difference of 92 cells/mm(2) (3.9%). The ANOVA based overall inter-rater
      reliability was 0.935. The algorithm was also capable of identifying all non
      processable images. Running times were in the order of 1-2 seconds per image.
      CONCLUSION: A new algorithm was developed for the fully automatic estimation of
      endothelial cell density. The results of a clinical evaluation on 100 corneas
      suggest that it is capable of reliably estimating endothelium cell density in
      donor corneas.

PMID- 15722311
TI  - Impact of lesion size on photodynamic therapy with verteporfin of predominantly
      classic lesions in age related macular degeneration.
AB  - AIM: To determine if photodynamic therapy (PDT) outcomes are related to lesion
      size in patients with subfoveal predominantly classic choroidal
      neovascularisation (CNV) secondary to age related macular degeneration (AMD).
      METHODS: According to greatest linear dimension (GLD) of the entire lesion
      determined with fluorescein angiography (FA) patients were divided into two
      groups. In the first group GLD was <3000 microm and in the second one GLD was
      3000-5000 microm. All eyes were treated with standard PDT with the verteporfin
      protocol. The primary outcome was the proportion of eyes in both groups that did
      not show significant leakage in FA at the end of follow up. Secondary outcomes
      were changes in GLD and in best corrected visual acuity (BCVA). RESULTS: 64
      patients (mean (SD) age, 76.7 (7.7) years; range 58-95 years) were recruited to
      participate in the study. All participants in the study completed the follow up
      time (mean 16.6 months). 24 patients (75%) in the group of smaller lesions (n =
      32) compared with 15 patients (46.8%) in the group of larger lesions (n = 32) did
      not show significant leakage in FA at the end of follow up (p = 0.02). A GLD
      increase >1000 microm was recorded in nine eyes (28.1%) in the group of smaller
      lesions and in 16 eyes (50%) in the group of larger lesions (p = 0.07). 22 eyes
      (68.7%) in the group of smaller lesions compared with 19 eyes (59.3%) in the
      group of larger lesions lost less than three lines of vision (p = 0.06). Relevant
      side effects related to verteporfin therapy were not recorded, except for four
      patients (6.2%) with infusion related back pain. CONCLUSIONS: These results
      suggest that lesion size at baseline may be a prognosis factor in PDT in patients
      with subfoveal predominantly classic CNV secondary to AMD. There are no relevant
      side effects or safety concerns derived from verteporfin therapy.

PMID- 15722312
TI  - Optical coherence tomography in photodynamic therapy for subfoveal choroidal
      neovascularisation secondary to age related macular degeneration: a cross
      sectional study.
AB  - AIMS: To introduce new terminology and validate its reliability for the analysis
      of optical coherence tomography (OCT) scans, compare clinical detection of
      cystoid macular oedema (CMO) and subretinal fluid (SRF) with OCT findings, and to
      study the effect of photodynamic therapy (PDT) on the foveal morphology. METHODS:
      Patients with subfoveal, predominantly classic choroidal neovascularisation (CNV)
      secondary to age related macular degeneration (AMD) undergoing PDT were evaluated
      with refraction protocol best corrected logMAR visual acuity (VA), slit lamp
      biomicroscopy, stereoscopic fluorescein angiography (FFA), and OCT. New
      terminologies introduced to interpret the OCT scans were: neuroretinal foveal
      thickness (NFT), bilaminar foveal thickness (BFT), outer high reflectivity band
      thickness (OHRBT), intraretinal fluid (IRF), subretinal fluid (oSRF), and
      vitreomacular hyaloid attachment (VMHA). RESULTS: Fifty six eyes of 53 patients
      were studied. VA was better in eyes with a thinner outer high reflectivity band
      (OHRBT) (p = 0.02) and BFT (p = 0.05). BFT was less in eyes that had undergone a
      greater number of PDT treatments (p = 0.04). There was poor agreement between OCT
      and clinical examination in the detection of CMO and subretinal fluid (kappa =
      0.289 and kappa = 0.165 respectively). To validate the interpretation and
      measurements on OCT, two groups of 20 scans were analysed by two independent
      observers. There was good agreement between the observers in the detection of
      IRF, oSRF, and VMHA (p<0.001). Measurements of NFT and BFT had a high
      reproducibility, and of OHRBT reproducibility was low. CONCLUSIONS: New
      terminology has been introduced and tested. OCT appears to be superior to
      clinical examination and FFA in the detection of CMO. In this study, better
      vision was associated with a thinner OHRBT and/or the absence of SRF giving
      insight into the biological effect of PDT.

PMID- 15722313
TI  - Diffuse diabetic macular oedema treated by intravitreal triamcinolone acetonide:
      a comparative, non-randomised study.
AB  - AIM: To report on visual outcome of patients receiving an intravitreal injection
      of triamcinolone acetonide for treatment of diffuse diabetic macular oedema.
      METHODS: Prospective, comparative, non-randomised clinical interventional study
      included 136 patients with diffuse diabetic macular oedema. Patients of the study
      group (97 eyes) received an intravitreal injection of 20-25 mg of triamcinolone
      acetonide and no other retinal treatment. Patients of the control group (69 eyes)
      received focal or panretinal laser treatment if indicated. Mean (standard
      deviation) follow up was 8.4 (SD 6.0) months (range 1.03-25.2 months). RESULTS:
      Visual acuity (VA) increased significantly (p<0.001) in the study group with 66
      (68%) eyes gaining in VA by at least two Snellen lines. In the control group, VA
      did not change significantly during the first 4 months of follow up, and
      decreased significantly (p<0.001) towards the end of the follow up. Difference in
      change of best VA was significant (p<0.001) between both groups. Correspondingly,
      the number of patients with VA improvement of two or more Snellen lines and
      visual loss of two or more Snellen lines, respectively, was significantly
      (p<0.001) higher and lower, respectively, in the study group. CONCLUSIONS:
      Intravitreal triamcinolone acetonide can temporarily increase VA in some patients
      with diffuse diabetic macular oedema.

PMID- 15722314
TI  - Late onset of rhegmatogenous retinal detachments after successful posterior
      segment intraocular foreign body removal.
AB  - BACKGROUND/AIM: A lack of data exists concerning the development of late
      postoperative, non-proliferative vitreoretinopathy (PVR), rhegmatogenous retinal
      detachments (RRDs) after successful posterior segment intraocular foreign body
      (PSIOFB) removal. The authors present a series of PSIOFB cases over several years
      with posterior hyaloid separation resulting in RRD in two patients, 4 and 8
      months after initial injury and vitrectomy. This report aims to increase
      awareness concerning the possibility of late RRDs complicating PSIOFB injuries
      and to emphasise careful long term observation. METHODS: Medical records of
      consecutive cases referred for presumed PSIOFB injury during a 4 year period were
      retrospectively reviewed. All eyes referred for presumed PSIOFB injuries were
      included. RESULTS: 11 patients were included in the series. Two patients had eyes
      so badly injured by large PSIOFBs that primary globe closure was followed within
      days by enucleation. Nine patients underwent pars plana vitrectomy for PSIOFB
      removal. Two patients experienced late RRDs that were managed with excellent long
      term visual outcomes. CONCLUSIONS: Late RRD may occur following successful
      removal of PSIOFBs, even several months after initial management. These RRDs may
      be successfully managed with a variety of methods, depending upon the extent and
      location of the detachment and causative break as well as surgeon comfort and
      preference.

PMID- 15722315
TI  - A detailed phenotypic study of "cone dystrophy with supernormal rod ERG".
AB  - AIMS: To characterise the detailed phenotype of "cone dystrophy with supernormal
      rod ERG" in a case series of 10 patients. METHODS: 10 affected patients were
      examined clinically and underwent colour fundus photography, with nine undergoing
      detailed electrophysiological testing. Five patients were assessed further with
      fundus autofluorescence (AF) imaging, automated photopic and dark adapted
      perimetry, and dark adaptometry. Detailed colour vision assessment was performed
      in six subjects. Blood samples were taken from four patients for DNA extraction
      and mutation screening of NR2E3 was undertaken. RESULTS: The onset of symptoms
      was in the first and second decades of life. Subjects presented with reduced
      central vision and marked photophobia. All individuals were myopic and colour
      vision testing revealed severely reduced colour discrimination predominantly
      along the red-green axes; tritan colour vision was relatively well preserved.
      Nyctalopia is a later feature of the disorder. Funduscopy and AF imaging revealed
      a range of macular appearances. There was electrophysiological evidence of marked
      macular dysfunction, reduced and delayed cone responses, and supernormal and
      delayed rod responses. Photopic and dark adapted perimetry revealed central
      scotomata with widespread peripheral sensitivity loss. No disease causing
      sequence variants in NR2E3 were identified. CONCLUSIONS: The largest case series
      to date has been described of the clinical, psychophysical and
      electrophysiological characteristics of this unusual cone dystrophy with
      supernormal rod responses. Electrophysiological data were consistent with a post
      phototransduction, but pre-inner nuclear layer, site of dysfunction. While the
      definitive diagnosis can only be made with electrophysiological testing, several
      characteristics that may increase suspicion of this diagnosis are presented.

PMID- 15722316
TI  - Interpreting the multifocal visual evoked potential: the effects of refractive
      errors, cataracts, and fixation errors.
AB  - AIM: To understand how refractive errors, cataracts, and fixation errors affect
      multifocal visual evoked potential (mfVEP) responses. METHODS: Monocular mfVEP
      responses were obtained using a pattern reversal dartboard display. For the
      control condition, visual acuity was corrected to > or =20/20 and foveal fixation
      was maintained. The right eye was tested under the following conditions:
      simulated refractive error, simulated cataract, steady eccentric fixation, and
      unsteady fixation. RESULTS: No subject demonstrated significant abnormalities
      under control conditions. For the simulated refractive error condition,
      significant centrally located abnormalities were seen for all subjects. For the
      simulated cataract condition, significant abnormalities were found for three
      subjects. The steady eccentric fixation condition yielded abnormalities in both
      eyes for all subjects while the unsteady fixation condition yielded significant
      central abnormalities in the tested eye. With eccentric and unsteady fixation
      conditions, all subjects had at least one sector with a waveform polarity
      reversal. CONCLUSIONS: While the mfVEP is a useful tool for identifying local
      optic nerve damage or ruling out non-organic aetiology of visual field defects,
      factors such as uncorrected refractive errors, cataract, eccentric fixation, and
      unsteady fixation can produce apparent field defects on the mfVEP. With care,
      these problems can be correctly identified.

PMID- 15722317
TI  - Measurement of stray light and glare: comparison of Nyktotest, Mesotest, stray
      light meter, and computer implemented stray light meter.
AB  - AIM: To evaluate the properties of devices for measuring stray light and glare:
      the Nyktotest, Mesotest, "conventional" stray light meter and a new, computer
      implemented version of the stray light meter. METHODS: 112 subjects, divided in
      three groups: (1) young subjects without any eye disease; (2) elderly subjects
      without any eye disease, and (3) subjects with (early) cataract in at least one
      eye. All subjects underwent a battery of glare and stray light tests, measurement
      of visual acuity, contrast sensitivity, refraction, and LOCS III cataract
      classification. Subjects answered a questionnaire on perceived disability during
      driving. RESULTS: Repeatability values were similar for all glare/stray light
      tests. Validity (correlation with LOCS III and questionnaire scores),
      discriminative ability (ability to discriminate between the three groups), and
      added value (to measurement of visual acuity and contrast sensitivity) were all
      superior for both stray light meters. Results of successive measurements are
      interrelated for the conventional but not the new stray light meter. This
      indicates a better resistance to fraud for the latter device. CONCLUSIONS: The
      new computer implemented stray light meter is the most promising device for
      future stray light measurements.

PMID- 15722318
TI  - Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of
      the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its
      prognostic significance in 136 cases.
AB  - AIM: To determine (a) the expression of plasma cell related antigens in
      extranodal marginal zone B cell lymphomas (EMZL) of the ocular adnexa; and (b)
      the prognostic value of plasmacellular differentiation in these tumours. METHODS:
      A consecutive case series of 136 ocular adnexal EMZL obtained from three ocular
      pathology centres over 20 years was analysed retrospectively. An extensive
      immunohistochemical panel, including the plasma cell related antigens VS38c,
      CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding
      protein (CBP) was performed. EMZL were defined as "plasmacellular differentiated"
      on the basis of morphological features, evidence of cytoplasmic immunoglobulin,
      negativity for BSAP/PAX5, and expression of at least one of the investigated
      plasma cell related antigens. Controls included normal or hyperplastic lymphatic
      tissues. Detailed clinical data were collected for most patients, and compared
      with the results of immunohistochemistry. The end points considered for
      statistical analysis were development of local tumour recurrence, development of
      systemic disease, and lymphoma related death. RESULTS: 57 (42%) of the 136 ocular
      adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid
      cases were primary tumours. In contrast with most admixed normal plasma cells,
      which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the
      plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all
      five plasma cell related antigens in only six of 57 (11%) plasmacellular
      differentiated ocular adnexal EMZL. The most commonly expressed plasma cell
      related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%)
      plasmacellular differentiated EMZL examined. Although the association of
      plasmacellular differentiation in primary ocular adnexal EMZL and disseminated
      disease was statistically significant on univariate analysis (p = 0.042), this
      was weaker on multivariate analysis. CONCLUSION: Plasmacellular differentiated
      tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell
      related antigens when compared with normal plasma cells. On multivariate
      analysis, plasmacellular differentiation in ocular adnexal EMZL was not
      significantly associated with local recurrence, the development of systemic
      disease, or with lymphoma related death.

PMID- 15722319
TI  - Impact of unilateral and bilateral vision loss on quality of life.
AB  - AIM: To investigate whether unilateral vision loss reduced any aspects of quality
      of life in comparison with normal vision and to compare its impact with that of
      bilateral vision loss. METHODS: This study used cluster stratified random sample
      of 3271 urban participants recruited between 1992 and 1994 for the Melbourne
      Visual Impairment Project. All predictors and outcomes were from the 5 year
      follow up examinations conducted in 1997-9. RESULTS: There were 2530 participants
      who attended the follow up survey and had measurement of presenting visual
      acuity. Both unilateral and bilateral vision loss were significantly associated
      with increased odds of having problems in visual functions including reading the
      telephone book, newspaper, watching television, and seeing faces. Non-correctable
      by refraction unilateral vision loss increased the odds of falling when away from
      home (OR = 2.86, 95% CI 1.16 to 7.08), getting help with chores (OR = 3.09, 95%
      CI 1.40 to 6.83), and becoming dependent (getting help with meals and chores) (OR
      = 7.50, 95% CI 1.97 to 28.6). Non-correctable bilateral visual loss was
      associated with many activities of daily living except falling. CONCLUSIONS: Non
      correctable unilateral vision loss was associated with issues of safety and
      independent living while non-correctable bilateral vision loss was associated
      with nursing home placement, emotional wellbeing, use of community services, and
      activities of daily living. Correctable or treatable vision loss should be
      detected and attended to.

PMID- 15722320
TI  - Non-specific tolerance induced by staphylococcal enterotoxin B in treating high
      risk corneal transplantation in rats.
AB  - AIMS: To explore the role of staphylococcal enterotoxin B (SEB) in treating high
      risk corneal keratoplasty in rats. METHODS: Rat corneal high risk transplantation
      rejection models were set up using Fisher 344 and Lewis rats. The experimental
      rats were injected intraperitoneally with 0.2 ml SEB at different concentrations
      before keratoplasty. The rejection indexes of the allograft were recorded and the
      lymphocyte infiltration in the allograft and the percentage of the lymphocyte
      subpopulation in the lymphatic organs were also examined. Lymphocyte
      proliferation ability and the concentration of IL-2 and IL-10 in the serum were
      also evaluated. RESULTS: Compared with the control group, SEB prolonged the
      survival time of the allograft significantly from 7 to 12 days. It could also
      reduce CD4(+) and CD8(+) lymphocyte infiltration in the allograft and minimise
      the percentage of CD4(+) and CD8(+) lymphocytes in the lymphatic organs. The
      lymphocyte proliferation ability was also weakened. However, the percentage of
      CD4(+) NK T lymphocytes in the lymphatic organs was raised. The serum
      concentration of IL-10 was higher but IL-2 was lower in the SEB treated groups.
      CONCLUSIONS: SEB prolonged the survival time of the allograft in high risk rat
      corneal allo-transplantation, which may be caused by T cell deletion and
      acquisition of non-specific tolerance.

PMID- 15722321
TI  - Choroidal dendritic cells require activation to present antigen and resident
      choroidal macrophages potentiate this response.
AB  - BACKGROUND/AIM: The uveal compartment of the eye contains extensive networks of
      resident macrophages and dendritic cells. These cells are now recognised to have
      a role in many ocular pathologies. The aim of this study was to isolate,
      characterise, and compare the function of ciliary body/choroid dendritic cells
      and macrophages from the normal eye. METHODS: Explants of rat and human ciliary
      body/choroid were cultured in vitro for various periods of time and cells
      harvested either from the supernatant fluid or from enzyme digested and washed
      explants. The cells were then phenotyped by microscopy and flow cytometry,
      examined by video time lapse photomicroscopy, and analysed functionally in a
      series of immunoassays. RESULTS: Two main types of dendritic cell were
      identified: large veil-like MHC class II(mid) motile but relatively non
      translocatory cells and small MHC class II(hi) motile and rapidly translocating
      cells. Tissue macrophages mainly remained associated with the explants in culture
      but gradually lost their resident tissue marker (ED2) and detached from the
      explants as clusters of low density, large, CR3 (ED7)(+) cells, some of which
      underwent apoptosis. Video time lapse studies showed dendritic cells constantly
      interacting with large single cells and cell clusters by traversing the
      interstices of the cell clusters. In functional studies, freshly isolated
      dendritic cells were poor presenters of antigen and required activation by short
      term culture for acquisition of antigen presenting function. In contrast,
      dendritic cell depleted choroidal cell preparations containing macrophages and
      other cells failed to present antigen even after short term culture but augmented
      the antigen presenting function of dendritic cells when tested in co-culture.
      CONCLUSION: At least two types of dendritic cells are present in the normal
      ciliary body/choroid layer of the eye. It is likely that these cells have
      different functions based on their motility and potential to migrate to secondary
      lymphoid tissue either during normal physiological homeostatic processes or
      during an inflammatory response. The behaviour of resident tissue myeloid cells
      may decide the outcome of the organism's response to stress, foreign antigen, and
      ageing processes such as age related macular degeneration.

PMID- 15722322
TI  - Epidemiology for ophthalmologists: an introduction to concepts, study designs,
      and interpreting findings.
AB  - This review provides an overview of the types of information epidemiological
      research can provide and how these data can be used. The aim is to provide the
      readers with basic epidemiological skills to allow them to read critically
      scientific articles and to gain proficiency in communicating about
      epidemiological research. All examples in the review are drawn from the
      ophthalmic literature. The first part of the review is relatively conceptual and
      focuses on epidemiological theory, including case definition, measures of the
      burden of disease, sampling and the interpretation of results. In the second part
      different study designs are described--specifically, cross sectional surveys,
      cohort studies, case-control studies, and randomised controlled trials, and the
      strengths and limitations of each highlighted.

PMID- 15722323
TI  - Solitary CD30+ anaplastic large cell lymphoma of the eyelid showing regression.

PMID- 15722324
TI  - Intravitreal triamcinolone acetonide and central serous chorioretinopathy.

PMID- 15722325
TI  - Choroidal translocation with a pedicle following excision of a type 1 choroidal
      neovascular membrane.

PMID- 15722326
TI  - Vascular occlusion in serpiginous choroidopathy.

PMID- 15722327
TI  - Persistent acanthamoeba keratitis in a non-contact lens wearer following exposure
      to bird seed dust.

PMID- 15722328
TI  - Brinzolamide induced reversible corneal decompensation.

PMID- 15722329
TI  - An unusual cause of acquired horizontal diplopia in a young adult.

PMID- 15722330
TI  - Use of scanning laser ophthalmoscopy in visual conversion reaction.

PMID- 15722331
TI  - Korean kindergarten vision screen programme.

PMID- 15722332
TI  - Comments on using fibrin glue in pterygium surgery.

PMID- 15722333
TI  - The severe acute respiratory syndrome coronavirus in tears.

PMID- 15722334
TI  - IVF and retinoblastoma.

PMID- 15722335
TI  - Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in
      myotonic dystrophy cells.
AB  - Small interfering RNA (siRNA) duplexes induce the specific cleavage of target
      RNAs in mammalian cells. Their involvement in down-regulation of gene expression
      is termed RNA interference (RNAi). It is widely believed that RNAi predominates
      in the cytoplasm. We report here the co-existence of cytoplasmic and nuclear RNAi
      phenomena in primary human myotonic dystrophy type 1 (DM1) cells by targeting
      myotonic dystrophy protein kinase (DMPK) mRNAs. Heterozygote DM1 myoblasts from a
      human DM1 fetus produce a nuclear retained mutant DMPK transcript with large CUG
      repeats ( approximately 3,200) from one allele of the DMPK gene and a wild type
      transcript with 18 CUG repeats, thus providing for both a nuclear and cytoplasmic
      expression profile to be evaluated. We demonstrate here for the first time down
      regulation of the endogenous nuclear retained mutant DMPK mRNAs targeted with
      lentivirus-delivered short hairpin RNAs (shRNAs). This nuclear RNAi(-like)
      phenomenon was not observed when synthetic siRNAs were delivered by cationic
      lipids, suggesting either a link between processing of the shRNA and nuclear
      import or a separate pathway for processing shRNAs in the nuclei. Our observation
      of simultaneous RNAi on both cytoplasmic and nuclear retained DMPK has important
      implications for post-transcriptional gene regulation in both compartments of
      mammalian cells.

PMID- 15722336
TI  - The manganese-stabilizing protein is required for photosystem II
      assembly/stability and photoautotrophy in higher plants.
AB  - Interfering RNA was used to suppress the expression of two genes that encode the
      manganese-stabilizing protein of photosystem II in Arabidopsis thaliana, MSP-1
      (encoded by psbO-1, At5g66570), and MSP-2 (encoded by psbO-2, At3g50820). A
      phenotypic series of transgenic plants was recovered that expressed high,
      intermediate, and low amounts of these two manganese-stabilizing proteins.
      Chlorophyll fluorescence induction and decay analyses were performed. Decreasing
      amounts of expressed protein led to the progressive loss of variable fluorescence
      and a marked decrease in the fluorescence quantum yield (F(v)/F(m)) in both the
      absence and the presence of dichloromethylurea. This result indicated that the
      amount of functional photosystem II reaction centers was compromised in the
      plants that exhibited intermediate and low amounts of the manganese-stabilizing
      proteins. An analysis of the decay of the variable fluorescence in the presence
      of dichlorophenyldimethylurea indicated that charge recombination between Q ((A
      )) and the S(2) state of the oxygen-evolving complex was seriously retarded in
      the plants that expressed low amounts of the manganese stabilizing proteins. This
      may have indicated a stabilization of the S(2) state in the absence of the
      extrinsic component. Immunological analysis of the photosystem II protein
      complement indicated that significant losses of the CP47, CP43, and D1 proteins
      occurred upon the loss of the manganese-stabilizing proteins. This indicated that
      these extrinsic proteins were required for photosystem II core
      assembly/stability. Additionally, although the quantity of the 24-kDa extrinsic
      protein was only modestly affected by the loss of the manganese-stabilizing
      proteins, the 17-kDa extrinsic protein dramatically decreased. The control
      proteins ribulose bisphosphate carboxylase and cytochrome f were not affected by
      the loss of the manganese-stabilizing proteins; the photosystem I PsaB protein,
      however, was significantly reduced in the low expressing transgenic plants.
      Finally, it was determined that the transgenic plants that expressed low amounts
      of the manganese-stabilizing proteins could not grow photoautotrophically.

PMID- 15722337
TI  - Phosphorylation of grb10 regulates its interaction with 14-3-3.
AB  - Grb10 is a member of adapter proteins that are thought to play a role in receptor
      tyrosine kinase-mediated signal transduction. Grb10 expression levels can
      influence Akt activity, and Grb10 may act as an adapter involved in the
      relocalization of Akt to the cell membrane. Here we identified 14-3-3 as a
      binding partner of Grb10 by employing a yeast two-hybrid screen. The 14-3-3.Grb10
      interaction requires phosphorylation of Grb10, and only the phosphorylated form
      of Grb10 co-immunoprecipitates with endogenous 14-3-3. We could identify a
      putative phosphorylation site in Grb10, which is located in a classical 14-3-3
      binding motif, RSVSEN. Mutation of this site in Grb10 diminished binding to 14-3
      3. Thus, Grb10 exists in two different states of phosphorylation and complexes
      with 14-3-3 when phosphorylated on serine 428. We provide evidence that Akt
      directly binds Grb10 and is able to phosphorylate Grb10 in an in vitro kinase
      assay. Based on these findings, we propose a regulatory circuitry involving a
      phosphorylation-regulated complex formation of Grb10 with 14-3-3 and Akt.

PMID- 15722338
TI  - Quantitative deuterium isotopic profiling at natural abundance indicates
      mechanistic differences for delta 12-epoxidase and delta 12-desaturase in
      Vernonia galamensis.
AB  - Quantitative (2)H NMR spectroscopy can determine the natural abundance
      ((2)H/(1)H) ratio at each site of a molecule. In natural products, variation in
      these values is related to the reaction mechanisms in the pertinent biosynthetic
      pathway. For the first time, this novel approach has been exploited to probe for
      mechanistic differences in the introduction of different functionalities into a
      long-chain fatty acid. Vernolic acid, a major component of the seed oil of
      Vernonia galamensis, contains both an epoxide and a desaturation. The site
      specific isotopic distribution ((2)H/(1)H)(i) has been determined for both
      vernolic acid and linoleic acid isolated from the same V. galamensis oil. It is
      found that the ((2)H/(1)H) ratio of vernolic acid shows a pattern along the
      entire length of the chain, consistent with linoleic acid being its immediate
      precursor. Notably, the C13 relates to the C13 of linoleic acid but not to the
      C13 of oleic acid. Furthermore, the C12 and C13 positions in vernolic acid are
      less depleted, consistent with a change in hybridization state from sp(2) to
      sp(3). However, the C11 position shows a marked relative enrichment in the
      vernolic acid, implying that it plays a role in the epoxidase but not the
      desaturase mechanism. Thus, although it can be concluded that the catalytic
      mechanisms for the epoxidase and desaturase activities are similar, marked
      differences in the residual ((2)H/(1)H) patterns indicate that the reaction
      mechanisms are not identical.

PMID- 15722339
TI  - REL1, a homologue of Drosophila dorsal, regulates toll antifungal immune pathway
      in the female mosquito Aedes aegypti.
AB  - Signaling by Drosophila Toll pathway activates two Rel/NF-kappaB transcription
      factors, Dorsal (Dl) and Dorsal-related immune factor (Dif). Dl plays a central
      role in the establishment of dorsoventral polarity during early embryogenesis,
      whereas Dif mediates the Toll receptor-dependent antifungal immune response in
      adult Drosophila. The absence of a Dif ortholog in mosquito genomes suggests that
      Dl may play its functional role in the mosquito Toll-mediated innate immune
      responses. We have cloned and molecularly characterized the gene homologous to
      Drosophila Dl and to Anopheles gambiae REL1 (Gambif1) from the yellow fever
      mosquito Aedes aegypti, named AaREL1. AaREL1 alternative transcripts encode two
      isoforms, AaREL1-A and AaREL1-B. Both transcripts are enriched during
      embryogenesis and are inducible by septic injury in larval and female mosquitoes.
      AaREL1 and AaREL2 (Aedes Relish) selectively bind to different kappaB motifs from
      insect immune gene promoters. Ectopic expression of AaREL1-A in both Drosophila
      mbn-2 cells and transgenic flies specifically activates Drosomycin and results in
      increased resistance against the fungus Beauveria bassiana. AaREL1-B acted
      cooperatively with AaREL1-A to enhance the immune gene activation in Aag-2 cells.
      The RNA interference knock-outs revealed that AaREL1 affected the expression of
      Aedes homologue of Drosophila Serpin-27A and mediated specific antifungal immune
      response against B. bassiana. These results indicate that the homologue of Dl,
      but not that of Dif, is a key regulator of the Toll antifungal immune pathway in
      A. aegypti female mosquitoes.

PMID- 15722340
TI  - Biphasic currents evoked by chemical or thermal activation of the heat-gated ion
      channel, TRPV3.
AB  - 2-Aminoethyl diphenylborinate was recently identified as a chemical activator of
      TRPV1, TRPV2, and TRPV3, three heat-gated members of the transient receptor
      potential vanilloid (TRPV) ion channel subfamily. Here we demonstrated that two
      structurally related compounds, diphenylboronic anhydride (DPBA) and
      diphenyltetrahydrofuran (DPTHF), can also modulate the activity of these
      channels. DPBA acted as a TRPV3 agonist, whereas DPTHF exhibited prominent
      antagonistic activity. However, all three diphenyl-containing compounds promoted
      some degree of channel activation or potentiation, followed by channel block.
      Strong TRPV3 activation by DPBA often leads to the appearance of a secondary,
      enhanced, current phase. A similar biphasic response was observed during TRPV3
      heat stimulation; an initial, gradually sensitizing phase (I(1)) was followed by
      an abrupt transition to a secondary phase (I(2)). I(2) was characterized by
      larger current amplitude, loss of outward rectification, and alterations in the
      following properties: permeability among cations; ruthenium red and DPTHF
      sensitivity; temperature dependence; and voltage-dependent gating. The I(1) to
      I(2) transition depended strongly on TRPV3 current density. Removal of
      extracellular divalent cations resulted in heat-evoked currents resembling I(2),
      whereas mutation of a putative Ca(2+)-binding residue in the pore loop domain,
      aspartate 641, facilitated detection of the I(1) to I(2) transition, suggesting
      that the conversion to I(2) resulted from the agonist- and time-dependent loss of
      divalent cationic inhibition. Primary keratinocytes overexpressing exogenous
      TRPV3 also exhibited biphasic agonist-evoked currents. Thus, strong activation by
      either chemical or thermal stimuli led to biphasic TRPV3 signaling behavior that
      may be associated with changes in the channel pore.

PMID- 15722341
TI  - cGMP inhibition of Na+/H+ antiporter 3 (NHE3) requires PDZ domain adapter NHERF2,
      a broad specificity protein kinase G-anchoring protein.
AB  - Electroneutral NaCl absorption mediated by Na+/H+ exchanger 3 (NHE3) is important
      in intestinal and renal functions related to water/Na+ homeostasis. cGMP inhibits
      NHE3 in intact epithelia. However, unexpectedly it failed to inhibit NHE3 stably
      transfected in PS120 cells, even upon co-expression of cGMP-dependent protein
      kinase type II (cGKII). Additional co-expression of NHERF2, the tandem PDZ domain
      adapter protein involved in cAMP inhibition of NHE3, restored cGMP as well as
      cAMP inhibition, whereas NHERF1 solely restored cAMP inhibition. In vitro
      conditions were identified in which NHERF2 but not NHERF1 bound cGKII. The NHERF2
      PDZ2 C terminus, which binds NHE3, also bound cGKII. A non-myristoylated mutant
      of cGKII did not support cGMP inhibition of NHE3. Although cGKI also bound NHERF2
      in vitro, it did not evoke inhibition of NHE3 unless a myristoylation site was
      added. These results show that NHERF2, acting as a novel protein kinase G
      anchoring protein, is required for cGMP inhibition of NHE3 and that cGKII must be
      bound both to the plasma membrane by its myristoyl anchor and to NHERF2 to
      inhibit NHE3.

PMID- 15722342
TI  - EphB receptor-binding peptides identified by phage display enable design of an
      antagonist with ephrin-like affinity.
AB  - The Eph receptor tyrosine kinases are overexpressed in many pathologic tissues
      and have therefore emerged as promising drug target candidates. However, there
      are few molecules available that can selectively bind to a single Eph receptor
      and not other members of this large receptor family. Here we report the
      identification by phage display of peptides that bind selectively to different
      receptors of the EphB class, including EphB1, EphB2, and EphB4. Peptides with the
      same EphB receptor specificity compete with each other for binding, suggesting
      that they have partially overlapping binding sites. In addition, several of the
      peptides contain amino acid motifs found in the G-H loop of the ephrin-B ligands,
      which is the region that mediates high-affinity interaction with the EphB
      receptors. Consistent with targeting the ephrin-binding site, the higher affinity
      peptides antagonize ephrin binding to the EphB receptors. We also designed an
      optimized EphB4-binding peptide with affinity comparable with that of the natural
      ligand, ephrin-B2. These peptides should be useful as selective inhibitors of the
      pathological activities of EphB receptors and as targeting agents for imaging
      probes and therapeutic drugs.

PMID- 15722343
TI  - The human hyaluronan synthase 2 gene is a primary retinoic acid and epidermal
      growth factor responding gene.
AB  - Hyaluronan is an abundant and rapidly turned over matrix molecule between the
      vital cell layers of the epidermis and subject to large concentration changes
      associated with keratinocyte proliferation, migration, and differentiation
      induced by paracrine and endocrine factors like epidermal growth factor (EGF) and
      all-trans-retinoic acid (RA). We found that in REK cells EGF and all-trans-RA up
      regulated hyaluronan synthase 2 (Has2) gene expression within 2 h 4-fold each and
      in HaCaT human immortal keratinocytes 8- and 33-fold, respectively. The first 10
      kb of the human Has2 promoter were scanned in silico and in vitro for potential
      response elements of signal transducer and activator of transcription (STAT) or
      RA receptor (RAR) proteins. We identified a STAT-response element in the proximal
      promoter region and confirmed its functionality in response to EGF by chromatin
      immunoprecipitation (ChIP) assays. Direct in vitro binding of RARs to four RARE
      candidates within the Has2 promoter could not be observed at stringent gel shift
      conditions, but reporter gene assays demonstrated functionality of a complex of
      two of these RAREs located approximately 1200 bp upstream of the transcription
      start site. Moreover, ChIP assays using antibodies against nine nuclear proteins
      monitored all-trans-RA-dependent binding of RAR, retinoid X receptor, mediator
      protein, and RNA polymerase II and also histone 4 acetylation to a promoter
      region containing the complex RARE. Taken together, the human Has2 gene is a
      potent primary EGF and all-trans-RA responding gene with a complex regulation.

PMID- 15722344
TI  - An activation switch in the rhodopsin family of G protein-coupled receptors: the
      thyrotropin receptor.
AB  - We aimed at understanding molecular events involved in the activation of a member
      of the G protein-coupled receptor family, the thyrotropin receptor. We have
      focused on the transmembrane region and in particular on a network of polar
      interactions between highly conserved residues. Using molecular dynamics
      simulations and site-directed mutagenesis techniques we have identified residue
      Asn-7.49, of the NPxxY motif of TM 7, as a molecular switch in the mechanism of
      thyrotropin receptor (TSHr) activation. Asn-7.49 appears to adopt two different
      conformations in the inactive and active states. These two states are
      characterized by specific interactions between this Asn and polar residues in the
      transmembrane domain. The inactive gauche+ conformation is maintained by
      interactions with residues Thr-6.43 and Asp-6.44. Mutation of these residues into
      Ala increases the constitutive activity of the receptor by factors of
      approximately 14 and approximately 10 relative to wild type TSHr, respectively.
      Upon receptor activation Asn-7.49 adopts the trans conformation to interact with
      Asp-2.50 and a putatively charged residue that remains to be identified. In
      addition, the conserved Leu-2.46 of the (N/S)LxxxD motif also plays a significant
      role in restraining the receptor in the inactive state because the L2.46A
      mutation increases constitutive activity by a factor of approximately 13 relative
      to wild type TSHr. As residues Leu-2.46, Asp-2.50, and Asn-7.49 are strongly
      conserved, this molecular mechanism of TSHr activation can be extended to other
      members of the rhodopsin-like family of G protein-coupled receptors.

PMID- 15722345
TI  - Polyribosome binding by GCN1 is required for full activation of eukaryotic
      translation initiation factor 2{alpha} kinase GCN2 during amino acid starvation.
AB  - The protein kinase GCN2 mediates translational control of gene expression in
      amino acid-starved cells by phosphorylating eukaryotic translation initiation
      factor 2alpha. In Saccharomyces cerevisiae, activation of GCN2 by uncharged tRNAs
      in starved cells requires its direct interaction with both the GCN1.GCN20
      regulatory complex and ribosomes. GCN1 also interacts with ribosomes in cell
      extracts, but it was unknown whether this activity is crucial for its ability to
      stimulate GCN2 function in starved cells. We describe point mutations in two
      conserved, noncontiguous segments of GCN1 that lead to reduced polyribosome
      association by GCN1.GCN20 in living cells without reducing GCN1 expression or its
      interaction with GCN20. Mutating both segments simultaneously produced a greater
      reduction in polyribosome binding by GCN1.GCN20 and a stronger decrease in
      eukaryotic translation initiation factor 2alpha phosphorylation than did mutating
      in one segment alone. These findings provide strong evidence that ribosome
      binding by GCN1 is required for its role as a positive regulator of GCN2. A
      particular mutation in the GCN1 domain, related in sequence to translation
      elongation factor 3 (eEF3), decreased GCN2 activation much more than it reduced
      ribosome binding by GCN1. Hence, the eEF3-like domain appears to have an effector
      function in GCN2 activation. This conclusion supports the model that an eEF3
      related activity of GCN1 influences occupancy of the ribosomal decoding site by
      uncharged tRNA in starved cells.

PMID- 15722346
TI  - Adenoviral gene transfer of the NF-kappa B inhibitory protein ABIN-1 decreases
      allergic airway inflammation in a murine asthma model.
AB  - Airway inflammation is a characteristic of many lung disorders, including asthma
      and chronic obstructive pulmonary disease. Using a murine model of allergen
      induced asthma, we have demonstrated that adenovirus-mediated delivery of the
      nuclear factor-kappaB (NF-kappaB) inhibitory protein ABIN-1 to the lung
      epithelium results in a considerable reduction of allergen-induced eosinophil
      infiltration into the lungs. This is associated with an ABIN-1-induced decrease
      in allergen-specific immunoglobulin E levels in serum, as well as a significant
      reduction of eotaxin, interleukin-4, and interleukin-1beta in bronchoalveolar
      lavage fluid. These findings not only prove that NF-kappaB plays a critical role
      in the pathogenesis of allergic inflammation but also illustrate that inhibiting
      NF-kappaB could have therapeutic value in the treatment of asthma and potentially
      other chronic inflammatory lung diseases.

PMID- 15722347
TI  - The C-terminal region of TIM17 links the outer and inner mitochondrial membranes
      in Arabidopsis and is essential for protein import.
AB  - The translocase of the inner membrane 17 (AtTIM17-2) protein from Arabidopsis has
      been shown to link the outer and inner mitochondrial membranes. This was
      demonstrated by several approaches: (i) In vitro organelle import assays
      indicated the imported AtTIM17-2 protein remained protease accessible in the
      outer membrane when inserted into the inner membrane. (ii) N-terminal and C
      terminal tagging indicated that it was the C-terminal region that was located in
      the outer membrane. (iii) Antibodies raised to the C-terminal 100 amino acids
      recognize a 31-kDa protein from purified mitochondria, but cross-reactivity was
      abolished when mitochondria were protease-treated to remove outer membrane
      exposed proteins. Antibodies to AtTIM17-2 inhibited import of proteins via the
      general import pathway into outer membrane-ruptured mitochondria, but did not
      inhibit protein import via the carrier import pathway. Together these results
      indicate that the C-terminal region of AtTIM17-2 is exposed on the outer surface
      of the outer membrane, and the C-terminal region is essential for protein import
      into mitochondria.

PMID- 15722348
TI  - Stable Golgi-mitochondria complexes and formation of Golgi Ca(2+) gradients in
      pancreatic acinar cells.
AB  - We have determined the localization of the Golgi with respect to other organelles
      in living pancreatic acinar cells and the importance of this localization to the
      establishment of Ca(2+) gradients over the Golgi. Using confocal microscopy and
      the Golgi-specific fluorescent probe 6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino)hexanoyl)sphingosine, we found Golgi structures localizing to the outer
      edge of the secretory granular region of individual acinar cells. We also
      assessed Golgi positioning in acinar cells located within intact pancreatic
      tissue using two-photon microscopy and found a similar localization. The
      mitochondria segregate the Golgi from lateral regions of the plasma membrane, the
      nucleus, and the basal part of the cytoplasm. The Golgi is therefore placed
      between the principal Ca(2+) release sites in the apical region of the cell and
      the important Ca(2+) sink formed by the peri-granular mitochondria. During
      acetylcholine-induced cytosolic Ca(2+) signals in the apical region, large Ca(2+)
      gradients form over the Golgi (decreasing from trans- to cis-Golgi). We further
      describe a novel, close interaction of the peri-granular mitochondria and the
      Golgi apparatus. The mitochondria and the Golgi structures form very close
      contacts, and these contacts remain stable over time. When the cell is forced to
      swell, the Golgi and mitochondria remain juxtaposed up to the point of cell
      lysis. The strategic position of the Golgi (closer to release sites than the bulk
      of the mitochondrial belt) makes this organelle receptive to local apical Ca(2+)
      transients. In addition the Golgi is ideally placed to be preferentially supplied
      by ATP from adjacent mitochondria.

PMID- 15722349
TI  - BACE1 cytoplasmic domain interacts with the copper chaperone for superoxide
      dismutase-1 and binds copper.
AB  - The amyloidogenic pathway leading to the production and deposition of Abeta
      peptides, major constituents of Alzheimer disease senile plaques, is linked to
      neuronal metal homeostasis. The amyloid precursor protein binds copper and zinc
      in its extracellular domain, and the Abeta peptides also bind copper, zinc, and
      iron. The first step in the generation of Abeta is cleavage of amyloid precursor
      protein by the aspartic protease BACE1. Here we show that BACE1 interacts with
      CCS (the copper chaperone for superoxide dismutase-1 (SOD1)) through domain I and
      the proteins co-immunoprecipitate from rat brain extracts. We have also been able
      to visualize the co-transport of membranous BACE1 and soluble CCS through axons.
      BACE1 expression reduces the activity of SOD1 in cells consistent with direct
      competition for available CCS as overexpression of CCS restores SOD1 activity.
      Finally, we demonstrate that the twenty-four residue C-terminal domain of BACE1
      binds a single Cu(I) atom with high affinity through cysteine residues.

PMID- 15722350
TI  - Pathway-specific profiling identifies the NF-kappa B-dependent tumor necrosis
      factor alpha-regulated genes in epidermal keratinocytes.
AB  - Identification of tumor necrosis factor alpha (TNF alpha) as the key agent in
      inflammatory disorders led to new therapies specifically targeting TNF alpha and
      avoiding many side effects of earlier anti-inflammatory drugs. However, because
      of the wide spectrum of systems affected by TNF alpha, drugs targeting TNF alpha
      have a potential risk of delaying wound healing, secondary infections, and
      cancer. Indeed, increased risks of tuberculosis and carcinogenesis have been
      reported as side effects after anti-TNF alpha therapy. TNF alpha regulates many
      processes (e.g. immune response, cell cycle, and apoptosis) through several
      signal transduction pathways that convey the TNF alpha signals to the nucleus.
      Hypothesizing that specific TNF alpha-dependent pathways control specific
      processes and that inhibition of a specific pathway may yield even more precisely
      targeted therapies, we used oligonucleotide microarrays and parthenolide, an NF
      kappa B-specific inhibitor, to identify the NF-kappa B-dependent set of the TNF
      alpha-regulated genes in human epidermal keratinocytes. Expression of
      approximately 40% of all TNF alpha-regulated genes depends on NF-kappa B; 17% are
      regulated early (1-4 h post-treatment), and 23% are regulated late (24-48 h).
      Cytokines and apoptosis-related and cornification proteins belong to the "early"
      NF-kappa B-dependent group, and antigen presentation proteins belong to the
      "late" group, whereas most cell cycle, RNA-processing, and metabolic enzymes are
      not NF-kappa B-dependent. Therefore, inflammation, immunomodulation, apoptosis,
      and differentiation are on the NF-kappa B pathway, and cell cycle, metabolism,
      and RNA processing are not. Most early genes contain consensus NF-kappaB binding
      sites in their promoter DNA and are, presumably, directly regulated by NF-kappa
      B, except, curiously, the cornification markers. Using siRNA silencing, we
      identified cFLIP/CFLAR as an essential NF-kappa B-dependent antiapoptotic gene.
      The results confirm our hypothesis, suggesting that inhibiting a specific TNF
      alpha-dependent signaling pathway may inhibit a specific TNF alpha-regulated
      process, leaving others unaffected. This could lead to more specific anti
      inflammatory agents that are both more effective and safer.

PMID- 15722351
TI  - Positively charged ceramide is a potent inducer of mitochondrial
      permeabilization.
AB  - Ceramide-induced cell death is thought to be mediated by change in mitochondrial
      function, although the precise mechanism is unclear. Proposed models suggest that
      ceramide induces cell death through interaction with latent binding sites on the
      outer or inner mitochondrial membranes, followed by an increase in membrane
      permeability, as an intermediate step in ceramide signal propagation. To
      investigate these models, we developed a new generation of positively charged
      ceramides that readily accumulate in isolated and in situ mitochondria.
      Accumulated, positively charged ceramides increased inner membrane permeability
      and triggered release of mitochondrial cytochrome c. Furthermore, the positively
      charged ceramide-induced permeability increase was suppressed by cyclosporin A
      (60%) and 1,3-dicyclohexylcarbodiimide (90%). These observations suggest that the
      inner membrane permeability increase is due to activation of specific ion
      transporters, not the generalized loss of lipid bilayer barrier functions. The
      difference in sensitivity of ceramide-induced ion fluxes to inhibitors of
      mitochondrial transporters suggests activation of at least two transport systems:
      the permeability transition pore and the electrogenic H(+) channel. Our results
      indicate the presence of specific ceramide targets in the mitochondrial matrix,
      the occupation of which triggers permeability alterations of the inner and outer
      mitochondrial membranes. These findings also suggest a novel therapeutic role for
      positively charged ceramides.

PMID- 15722353
TI  - A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is
      responsible for disproportionate dwarfism in cn/cn mouse.
AB  - The achondroplastic mouse is a spontaneous mutant characterized by
      disproportionate dwarfism with short limbs and tail due to disturbed
      chondrogenesis during endochondral ossification. These abnormal phenotypes are
      controlled by an autosomal recessive gene (cn). In this study, linkage analysis
      using 115 affected mice of F2 progeny mapped the cn locus on an approximately 0.8
      cM region of chromosome 4, and natriuretic peptide receptor 2 (Npr2) gene was
      identified as the most potent candidate for the cn mutant in this region. This
      gene encodes a receptor for C-type natriuretic peptide (CNP) that positively
      regulates longitudinal bone growth by producing cGMP in response to CNP binding
      to the extracellular domain. Sequence analyses of the Npr2 gene in cn/cn mice
      revealed a T to G transversion leading to the amino acid substitution of highly
      conserved Leu with Arg in the guanylyl cyclase domain. In cultured chondrocytes
      of cn/cn mice, stimulus with CNP did not significantly increase intracellular
      cGMP concentration, whereas it increased in +/+ mice. Transfection of the mutant
      Npr2 gene into COS-7 cells also showed similar results, indicating that the
      missense mutation of the Npr2 gene in cn/cn mice resulted in disruption of the
      guanylyl cyclase activity of the receptor. We therefore concluded that the dwarf
      phenotype of cn/cn mouse is caused by a loss-of-function mutation of the Npr2
      gene, and cn/cn mouse will be a useful model to further study the molecular
      mechanism regulating endochondral ossification by CNP/natriuretic peptide
      receptor B signal.

PMID- 15722352
TI  - P2Y6 nucleotide receptors activate NF-kappaB and increase survival of
      osteoclasts.
AB  - Nucleotides, released from cells during inflammation and by mechanical
      stimulation, act through the P2 family of nucleotide receptors. Previous studies
      have demonstrated the expression of P2Y1 and P2Y2 receptors in osteoclasts. The
      aim of this study was to determine whether osteoclast P2Y receptors signal
      through NF-kappaB, a key transcription factor regulating osteoclastogenesis.
      Immunofluorescence was used to detect the p65 subunit of NF-kappaB, which upon
      activation translocates from the cytosol to nuclei. Low levels of NF-kappaB
      activation were observed in untreated rabbit osteoclasts and in those exposed to
      2-methylthio ADP (P2Y1 agonist) or ATP or UTP (P2Y2 agonists). In contrast, UDP
      or INS48823 (P2Y6 agonists) induced a significant increase in the number of cells
      exhibiting NF-kappaB activation, a process sensitive to the proteasome inhibitor
      lactacystin. In osteoclasts purified by micromanipulation, reverse transcription
      PCR revealed the presence of P2Y1, P2Y2, and P2Y6 receptor transcripts, and
      application of agonists for these receptors induced the transient rise of
      cytosolic calcium. Treatment of rat osteoclasts with UDP or INS48823, but not 2
      methylthio ADP or UTP, increased osteoclast survival. Osteoprotegerin (a decoy
      receptor for RANK ligand) did not significantly alter the effects of UDP on NF
      kappaB localization or osteoclast survival, consistent with a direct action.
      Moreover, SN50 (cell-permeable peptide inhibitor of NF-kappaB) suppressed the
      enhancement of cell survival induced by UDP and INS48823. Our findings
      demonstrate the presence of functional P2Y6 receptors in osteoclasts. Thus,
      nucleotides, following their release at sites of inflammation and mechanical
      stimulation, can act through P2Y6 receptors to initiate NF-kappaB signaling and
      enhance osteoclast survival.

PMID- 15722354
TI  - The 14-3-3 protein translates the NA+,K+-ATPase {alpha}1-subunit phosphorylation
      signal into binding and activation of phosphoinositide 3-kinase during
      endocytosis.
AB  - Clathrin-dependent endocytosis of Na(+),K(+)-ATPase molecules in response to G
      protein-coupled receptor signals is triggered by phosphorylation of the alpha
      subunit and the binding of phosphoinositide 3-kinase. In this study, we describe
      a molecular mechanism linking phosphorylation of Na(+),K(+)-ATPase alpha-subunit
      to binding and activation of phosphoinositide 3-kinase. Co-immunoprecipitation
      studies, as well as experiments using confocal microscopy, revealed that dopamine
      favored the association of 14-3-3 protein with the basolateral plasma membrane
      and its co-localization with the Na(+),K(+)-ATPase alpha-subunit. The functional
      relevance of this interaction was established in opossum kidney cells expressing
      a 14-3-3 dominant negative mutant, where dopamine failed to decrease Na(+),K(+)
      ATPase activity and to promote its endocytosis. The phosphorylated Ser-18 residue
      within the alpha-subunit N terminus is critical for 14-3-3 binding. Activation of
      phosphoinositide 3-kinase by dopamine during Na(+),K(+)-ATPase endocytosis
      requires the binding of the kinase to a proline-rich domain within the alpha
      subunit, and this effect was blocked by the presence of a 14-3-3 dominant
      negative mutant. Thus, the 14-3-3 protein represents a critical linking mechanism
      for recruiting phosphoinositide 3-kinase to the site of Na(+),K(+)-ATPase
      endocytosis.

PMID- 15722355
TI  - Probucol protects against hypochlorite-induced endothelial dysfunction:
      identification of a novel pathway of probucol oxidation to a biologically active
      intermediate.
AB  - Atherosclerosis is associated with endothelial dysfunction and a heightened state
      of inflammation characterized, in part, by an increase in vascular
      myeloperoxidase and proteins modified by its principal oxidant, hypochlorous acid
      (HOCl). Here we examined whether probucol could protect against endothelial
      dysfunction induced by the two-electron oxidant HOCl. Hypochlorous acid
      eliminated endothelium-dependent relaxation of rabbit aorta, whereas endothelial
      function and tissue cGMP was preserved and elevated, respectively, in animals
      pretreated with probucol. Exogenously added probucol also protected against HOCl
      induced endothelial dysfunction. In vitro, HOCl oxidized probucol in a two-phase
      process with rate constants k(1) = 2.7 +/- 0.3 x 10(2) and k(2) = 0.7 +/- 0.2 x
      10(2) m(-1) s(-1) that resulted in a dose- and time-dependent accumulation of
      probucol-derived disulfoxide, 4,4'-dithiobis(2,6-di-tert-butyl-phenol) (DTBP),
      DTBP-derived thiosulfonate, disulfone, and sulfonic acid, together with 3,3',5,5'
      tetra-tert-butyl-4,4'-diphenoquinone (DPQ) as determined by high performance
      liquid chromatography and mass spectrometry. Like HOCl, selected one-electron
      oxidants converted probucol into DTBP and DPQ. Also, dietary and in vitro added
      DTBP protected aortic rings from HOCl-induced endothelial dysfunction and in
      vitro oxidation by HOCl gave rise to the thiosulfonate, disulfone, and sulfonic
      acid intermediates and DPQ. However, the product profiles of the in vitro
      oxidation systems were different from those in aortas of rabbits receiving
      dietary probucol or DTBP +/- HOCl treatment. Together, the results show that both
      probucol and DTBP react with HOCl and protect against HOCl-induced endothelial
      dysfunction, although direct scavenging of HOCl is unlikely to be responsible for
      the vascular protection by the two compounds.

PMID- 15722356
TI  - Redirection of eicosanoid metabolism in mPGES-1-deficient macrophages.
AB  - Microsomal prostaglandin E synthase (mPGES)-1 is one of several prostaglandin E
      synthases involved in prostaglandin H2 (PGH2) metabolism. In the present report,
      we characterize the contribution of mPGES-1 to cellular PGH2 metabolism in murine
      macrophages by studying the synthesis of eicosanoids and expression of eicosanoid
      metabolism enzymes in wild type and mPGES-1-deficient macrophages. Thioglycollate
      elicited macrophages isolated from mPGES-1-/- animals and genetically matched
      wild type controls were stimulated with diverse pro-inflammatory stimuli.
      Prostaglandins were released in the following order of decreasing abundance from
      wild type macrophages stimulated with lipopolysaccharide: prostaglandin E2
      (PGE2)>thromboxane B2 (TxB2)>6-keto prostaglandin F1alpha (PGF1alpha),
      prostaglandin F(2alpha) (PGF2alpha), and prostaglandin D2 (PGD2). In contrast, we
      detected in mPGES-1-/- macrophages a >95% reduction in PGE2 production resulting
      in the following altered prostaglandin profile: TxB2>6-keto PGF1alpha and
      PGF2alpha>PGE2, despite the comparable release of total prostaglandins. No
      significant change in expression pattern of key prostaglandin-synthesizing
      enzymes was detected between the genotypes. We then further profiled genotype
      related differences in the eicosanoid profile using macrophages pre-stimulated
      with lipopolysaccharide followed by a 10-min incubation with 10 microm
      [3H]arachidonic acid. Eicosanoid products were subsequently identified by reverse
      phase high pressure liquid chromatography. The dramatic reduction in [3H]PGE2
      formation from mPGES-1-/- macrophages compared with controls resulted in TxB2 and
      6-keto PGF1alpha becoming the two most abundant prostaglandins in these samples.
      Our results also suggest a 5-fold increase in 12-[3H]hydroxyheptadecatrienoic
      acid release in mPGES-1-/- samples. Our data support the hypothesis that mPGES-1
      induction in response to an inflammatory stimulus is essential for PGE2
      synthesis. The redirection of prostaglandin production in mPGES-1-/- cells
      provides novel insights into how a cell processes the unstable endoperoxide PGH2
      during the inactivation of a major metabolic outlet.

PMID- 15722357
TI  - The interaction of lipophilic drugs with intestinal fatty acid-binding protein.
AB  - Intestinal fatty acid-binding protein (I-FABP) is a small protein that binds long
      chain dietary fatty acids in the cytosol of the columnar absorptive epithelial
      cells (enterocytes) of the intestine. The binding cavity of I-FABP is much larger
      than is necessary to bind a fatty acid molecule, which suggests that the protein
      may be able to bind other hydrophobic and amphipathic ligands such as lipophilic
      drugs. Herein we describe the binding of three structurally diverse lipophilic
      drugs, bezafibrate, ibuprofen (both R- and S-isomers) and nitrazepam to I-FABP.
      The rank order of affinity for I-FABP determined for these compounds was found to
      be R-ibuprofen approximately bezafibrate > S-ibuprofen >> nitrazepam. The binding
      affinities were not directly related to aqueous solubility or partition
      coefficient of the compounds; however, the freely water-soluble drug diltiazem
      showed no affinity for I-FABP. Drug-I-FABP interaction interfaces were defined by
      analysis of chemical shift perturbations in NMR spectra, which revealed that the
      drugs bound within the central fatty acid binding cavity. Each drug participated
      in a different set of interactions within the cavity; however, a number of common
      contacts were observed with residues also involved in fatty acid binding. These
      data suggest that the binding of non-fatty acid lipophilic drugs to I-FABP may
      increase the cytosolic solubility of these compounds and thereby facilitate drug
      transport from the intestinal lumen across the enterocyte to sites of
      distribution and metabolism.

PMID- 15722358
TI  - Essential role for mitogen-activated protein (MAP) kinase phosphatase-1 in stress
      responsive MAP kinase and cell survival signaling.
AB  - Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) constitute a family
      of 11 dual-specificity phosphatases that inactivate the MAPKs by
      dephosphorylation. Although the contribution of MAPKs to cell growth and cell
      death has been examined extensively, it remains unclear whether MKPs play an
      essential role in the regulation of these processes. To clarify the role of MKP
      1, we determined the effects on the MAPKs and cell growth and death in primary
      fibroblasts derived from mice lacking MKP-1. Here we have shown that MKP-1 is
      critical for the inactivation of p38 MAPK and JNK following stimulation with
      serum, anisomycin, and osmotic stress. In addition, MKP-1 was identified as a
      critical negative regulator of the cAMP-mediated p38 MAPK pathway. MKP-1
      deficient mouse embryonic fibroblasts (MEFs) displayed enhanced p38 MAPK activity
      and cAMP-response element-dependent transcriptional activation in response to
      forskolin. Surprisingly, MKP-1-deficient fibroblasts exhibited reduced cell
      growth compared with wild type MEFs as a result of enhanced cell death. The
      enhanced level of cell death in MKP-1-deficient MEFs was rescued by SB203580, an
      inhibitor of p38 MAPK. MKP-1-deficient MEFs were also sensitive to anisomycin
      induced apoptosis. Collectively, these data demonstrate that MKP-1 promotes cell
      survival by attenuating stress-responsive MAPK-mediated apoptosis.

PMID- 15722359
TI  - Two proteins mediate class II ribonucleotide reductase activity in Pseudomonas
      aeruginosa: expression and transcriptional analysis of the aerobic enzymes.
AB  - The opportunistic human pathogen Pseudomonas aeruginosa is one of a few
      microorganisms that code for three different classes (I, II, and III) of the
      enzyme ribonucleotide reductase (RNR). Class II RNR of P. aeruginosa differs from
      all hitherto known class II enzymes by being encoded by two consecutive open
      reading frames denoted nrdJa and nrdJb and separated by 16 bp. Split nrdJ genes
      were also found in the few other gamma-proteobacteria that code for a class II
      RNR. Interestingly, the two genes encoding the split nrdJ in P. aeruginosa were
      co-transcribed, and both proteins were expressed. Exponentially growing aerobic
      cultures were predominantly expressing the class I RNR (encoded by the nrdAB
      operon) compared with the class II RNR (encoded by the nrdJab operon). Upon entry
      to stationary phase, the relative amount of nrdJa transcript increased about 6-7
      fold concomitant with a 6-fold decrease in the relative amount of nrdA
      transcript. Hydroxyurea treatment known to knock out the activity of class I RNR
      caused strict growth inhibition of P. aeruginosa unless 5'
      deoxyadenosylcobalamin, a cofactor specifically required for activity of class II
      RNRs, was added to the rich medium. Rescue of the hydroxyurea-treated cells in
      the presence of the vitamin B12 cofactor strongly implies that P. aeruginosa
      produces a functionally active NrdJ protein. Biochemical studies showed for the
      first time that presence of both NrdJa and NrdJb subunits were absolutely
      essential for enzyme activity. Based on combined genetic and biochemical results,
      we suggest that the two-component class II RNR in P. aeruginosa is primarily used
      for DNA repair and/or possibly DNA replication at low oxygen tension.

PMID- 15722360
TI  - Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic
      mechanism of soluble amyloid oligomers.
AB  - Increasing evidence suggests that amyloid peptides associated with a variety of
      degenerative diseases induce neurotoxicity in their intermediate oligomeric
      state, rather than as monomers or fibrils. To test this hypothesis and
      investigate the possible involvement of Ca2+ signaling disruptions in amyloid
      induced cytotoxicity, we made homogeneous preparations of disease-related
      amyloids (Abeta, prion, islet amyloid polypeptide, polyglutamine, and lysozyme)
      in various aggregation states and tested their actions on fluo-3-loaded SH-SY5Y
      cells. Application of oligomeric forms of all amyloids tested (0.6-6 microg ml-1)
      rapidly (approximately 5 s) elevated intracellular Ca2+, whereas equivalent
      amounts of monomers and fibrils did not. Ca2+ signals evoked by Abeta42 oligomers
      persisted after depletion of intracellular Ca2+ stores, and small signals
      remained in Ca2+-free medium, indicating contributions from both extracellular
      and intracellular Ca2+ sources. The increased membrane permeability to Ca2+
      cannot be attributed to activation of endogenous Ca2+ channels, because responses
      were unaffected by the potent Ca2+-channel blocker cobalt (20 microm). Instead,
      observations that Abeta42 and other oligomers caused rapid cellular leakage of
      anionic fluorescent dyes point to a generalized increase in membrane
      permeability. The resulting unregulated flux of ions and molecules may provide a
      common mechanism for oligomer-mediated toxicity in many amyloidogenic diseases,
      with dysregulation of Ca2+ ions playing a crucial role because of their strong
      trans-membrane concentration gradient and involvement in cell dysfunction and
      death.

PMID- 15722363
TI  - Evaluation of a regional community action intervention in New Zealand to improve
      age checks for young people purchasing alcohol.
AB  - This paper describes the evaluation of a regional community action intervention
      to reduce access to alcohol from off-license premises by minors. The intervention
      focussed on: (1) monitoring alcohol sales made without age identification from
      off-licenses; (2) utilizing data on alcohol sales for media advocacy and direct
      contact with alcohol retailers and (3) working with key enforcement staff to
      encourage increased monitoring and enforcement of minimum purchase age
      legislation for off-licenses. Evaluation of this intervention used a case study
      design. Purchase survey data was obtained before and after intervention. Media
      items were monitored and included pre- and post-intervention phases. Interviews,
      with key enforcement staff, and document review were undertaken post
      intervention. Purchase survey data showed a significant decrease (p < 0.05) in
      sales of alcohol made to young people without age identification pre- and post
      intervention. Pre-intervention: 60% of visits resulted in a sale made without age
      identification; post-intervention this proportion was 46%. Principal component
      analysis of newsprint media indicated increased coverage of items advocating
      improved age checking for off-licenses following intervention. Interview data and
      document review indicate that some enforcement staff in the region implemented
      increased enforcement strategies including, controlled purchase operations and
      increased visits to off-licenses due to the intervention. Evaluation findings
      indicate that collaborative and intersectoral community action interventions
      implemented regionally can be effective in redirecting resources to achieve
      preventive outcomes at a population level.

PMID- 15722361
TI  - MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand,
      promotes human osteoclast fusion, and rescues granulocyte macrophage colony
      stimulating factor suppression of osteoclast formation.
AB  - Human osteoclast formation from monocyte precursors under the action of receptor
      activator of nuclear factor-kappaB ligand (RANKL) was suppressed by granulocyte
      macrophage colony-stimulating factor (GM-CSF), with down-regulation of critical
      osteoclast-related nuclear factors. GM-CSF in the presence of RANKL and
      macrophage colony-stimulating factor resulted in mononuclear cells that were
      negative for tartrate-resistant acid phosphatase (TRAP) and negative for bone
      resorption. CD1a, a dendritic cell marker, was expressed in GM-CSF, RANKL, and
      macrophage colony-stimulating factor-treated cells and absent in osteoclasts.
      Microarray showed that the CC chemokine, monocyte chemotactic protein 1 (MCP-1),
      was profoundly repressed by GM-CSF. Addition of MCP-1 reversed GM-CSF suppression
      of osteoclast formation, recovering the bone resorption phenotype. MCP-1 and
      chemokine RANTES (regulated on activation normal T cell expressed and secreted)
      permitted formation of TRAP-positive multinuclear cells in the absence of RANKL.
      However, these cells were negative for bone resorption. In the presence of RANKL,
      MCP-1 significantly increased the number of TRAP-positive multinuclear bone
      resorbing osteoclasts (p = 0.008). When RANKL signaling through NFATc1 was
      blocked with cyclosporin A, both MCP-1 and RANTES expression was down-regulated.
      Furthermore, addition of MCP-1 and RANTES reversed the effects of cyclosporin A
      and recovered the TRAP-positive multinuclear cell phenotype. Our model suggests
      that RANKL-induced chemokines are involved in osteoclast differentiation at the
      stage of multinucleation of osteoclast precursors and provides a rationale for
      increased osteoclast activity in inflammatory conditions where chemokines are
      abundant.

PMID- 15722364
TI  - Towards a politics of health.
AB  - The importance of public policy as a determinant of health is routinely
      acknowledged, but there remains a continuing absence of mainstream debate about
      the ways in which the politics, power and ideology, which underpin public policy
      influence people's health. This paper explores the possible reasons behind the
      absence of a politics of health and demonstrates how explicit acknowledgement of
      the political nature of health will lead to more effective health promotion
      strategy and policy, and to more realistic and evidence-based public health and
      health promotion practice.

PMID- 15722365
TI  - Influence of known psychosocial smoking risk factors on Egyptian adolescents'
      cigarette smoking behavior.
AB  - The morbidity and mortality associated with cigarette smoking is shifting from
      the developed world to developing countries, especially developing Arab
      countries. One such country is Egypt, which has the highest rate of tobacco
      consumption in the Arab world. To curb the rising smoking epidemic in Egypt,
      appropriate adolescent smoking prevention programs need to be developed. Most of
      the effective adolescent smoking prevention programs are based on the social
      influence approach, which targets the proximal psychosocial variables believed to
      promote adolescent smoking. However, most of our understanding of adolescents'
      psychosocial smoking risk factors is based mainly on Western studies. Whether
      these factors have the same influence on Egyptian adolescents' smoking behavior
      has not been investigated to date. An understanding of the psychosocial
      correlates of smoking behavior among Egyptian adolescents may help in designing
      the appropriate smoking prevention program aimed at this population. This study
      reports the results of a cross-sectional survey administered to a random sample
      of 1930 students in grades 7, 9 and 12 in the city of Alexandria, Egypt, in May
      2003. Adolescent smoking behavior was positively associated with positive beliefs
      about smoking, sibling, parent and peer smoking, and social smoking norms, with
      sibling smoking and perceived adult smoking norms having a stronger influence on
      adolescents' smoking behavior than peer smoking and perceived peer smoking norms.
      Refusal self-efficacy was protective against smoking behavior, while knowledge of
      the short-term negative consequences of smoking was protective against
      susceptibility to future smoking among females only. The results suggest that
      adolescents from collective cultures, like Egypt, are more influenced by their
      family's smoking behavior and perceived adult smoking norms than their peers'
      smoking behavior and perceived peer smoking norms. Smoking prevention programs
      aimed at Egyptian adolescents should be accompanied by smoking cessation programs
      for the family and adult community members.

PMID- 15722366
TI  - Promoting active transport in a workplace setting: evaluation of a pilot study in
      Australia.
AB  - Promoting active transport is an increasingly important focus of recent health
      promotion initiatives addressing the major public health concerns of car
      dependence, decreased levels of physical activity and environmental health. Using
      active transport that relies less on the use of private cars and more on
      alternatives such as walking, cycling and public transport has the potential to
      increase population levels of physical activity and to improve the environment.
      Over 12 months, a combined social and individualized marketing campaign was
      delivered to a cohort of randomly selected health service employees (n = 68)
      working at a health care facility in inner-city Sydney, Australia. Pre- and post
      intervention surveys measured changes in mode of transport, awareness of active
      transport and attitudes towards mode of transport. Following the intervention, we
      found there was a reduction in the proportion of participants who drove to work 5
      days per week and a decrease in trips travelled by car on weekends. In addition,
      there was high awareness of the intervention amongst participants and their
      understanding of the concept of active transport improved from 17.6% at baseline
      to 94.1% at the follow-up survey (p < 0.01). There was also a significant shift
      in attitudes, which suggested increased positive regard for active transport. Our
      findings suggest that a combined social and individualized marketing campaign in
      the workplace setting can increase the use of active transport for the journey to
      work and trips on weekends. However, before these findings are widely applied,
      the intervention needs to be tested in a controlled study with a larger sample
      size.

PMID- 15722367
TI  - Food advertising on Australian television: the extent of children's exposure.
AB  - The objective of this study was to investigate the extent and nature of food
      advertising during Australian children's television (TV) viewing hours and
      programs, and to determine whether confectionery and fast food restaurant
      advertisements were more likely to be broadcast during children's programs than
      during adults' programs on Sydney television stations. One week (390 h) of
      Australian advertising data broadcast during children's TV viewing hours over 15
      television stations were analysed to determine the proportion of food
      advertisements and, in turn, the proportion of those advertisements promoting
      foods high in fat and/or sugar. One week (346 h) of confectionery and fast food
      restaurant advertisements broadcast over three Sydney television stations were
      analysed to determine whether these types of advertisements were more likely to
      be advertised during children's programs than adults' programs. Half of all food
      advertisements promoted foods high in fat and/or sugar. 'Confectionery' and 'fast
      food restaurants' were the most advertised food categories during children's TV
      viewing hours. Confectionery advertisements were three times as likely, and fast
      food restaurant advertisements twice as likely, to be broadcast during children's
      programs than adults' programs. It can be concluded that foods most advertised
      during children's viewing hours are not those foods that contribute to a healthy
      diet for children. Confectionery and fast food restaurant advertising appears to
      target children. Australian children need protection from the targeted promotion
      of unhealthy foods on television, but currently little exists.

PMID- 15722369
TI  - Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease:
      randomised double blind placebo controlled trial.
AB  - OBJECTIVES: To determine the respective efficacy of quetiapine and rivastigmine
      for agitation in people with dementia in institutional care and to evaluate these
      treatments with respect to change in cognitive performance. DESIGN: Randomised
      double blind (clinician, patient, outcomes assessor) placebo controlled trial.
      SETTING: Care facilities in the north east of England. PARTICIPANTS: 93 patients
      with Alzheimer's disease, dementia, and clinically significant agitation.
      INTERVENTION: Atypical antipsychotic (quetiapine), cholinesterase inhibitor
      (rivastigmine), or placebo (double dummy). MAIN OUTCOME MEASURES: Agitation
      (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery)
      at baseline and at six weeks and 26 weeks. The primary outcome was agitation
      inventory at six weeks. RESULTS: 31 patients were randomised to each group, and
      80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom
      71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26
      placebo). Compared with placebo, neither group showed significant differences in
      improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six
      patients scored > 10 on the severe impairment battery at baseline, 46 (82%) of
      whom were included in the analysis at six week follow up (14 rivastigmine, 14
      quetiapine, 18 placebo). For quetiapine the change in severe impairment battery
      score from baseline was estimated as an average of -14.6 points (95% confidence
      interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six
      weeks (P = 0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P = 0.01).
      The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower
      at six weeks (P = 0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P =
      0.3). CONCLUSIONS: Neither quetiapine nor rivastigmine are effective in the
      treatment of agitation in people with dementia in institutional care. Compared
      with placebo, quetiapine is associated with significantly greater cognitive
      decline.

PMID- 15722368
TI  - International retrospective cohort study of neural tube defects in relation to
      folic acid recommendations: are the recommendations working?
AB  - OBJECTIVES: To evaluate the effectiveness of policies and recommendations on
      folic acid aimed at reducing the occurrence of neural tube defects. DESIGN:
      Retrospective cohort study of births monitored by birth defect registries.
      SETTING: 13 birth defects registries monitoring rates of neural tube defects from
      1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales,
      Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia
      Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were
      ascertained among liveborn infants, stillbirths, and pregnancy terminations
      (where legal). Policies and recommendations were ascertained by interview and
      literature review. MAIN OUTCOME MEASURES: Incidences and trends in rates of
      neural tube defects before and after 1992 (the year of the first recommendations)
      and before and after the year of local recommendations (when applicable).
      RESULTS: The issuing of recommendations on folic acid was followed by no
      detectable improvement in the trends of incidence of neural tube defects.
      CONCLUSIONS: Recommendations alone did not seem to influence trends in neural
      tube defects up to six years after the confirmation of the effectiveness of folic
      acid in clinical trials. New cases of neural tube defects preventable by folic
      acid continue to accumulate. A reasonable strategy would be to quickly integrate
      food fortification with fuller implementation of recommendations on supplements.

PMID- 15722370
TI  - Impact of misclassification of in vitro fertilisation in studies of folic acid
      and twinning: modelling using population based Swedish vital records.
AB  - OBJECTIVE: To determine whether failure to adequately adjust for a reported 40%
      misclassification of use of in vitro fertilisation (IVF) as reported in a Swedish
      study could have led to a false finding that folic acid increases dizygotic
      twinning. DESIGN: Modelling with population based data. SETTING: Swedish vital
      records for 1995-9. MAIN OUTCOME MEASURES: Rates of twinning calculated according
      to whether women used IVF to become pregnant. Estimated unadjusted and adjusted
      odds ratios of the association between use of folic acid and twinning by use of
      IVF. RESULTS: In 1995-9, Swedish women who used IVF had an almost 20 times the
      chance of having twins than women who did not use IVF (rate ratio 19.7, 95%
      confidence interval 18.7 to 20.6). In the absence of a true effect of folic acid,
      the use of a 40% misclassified surrogate variable to adjust for use of IVF would
      have resulted in a false finding that folic acid was associated with a more than
      twofold increase in twinning. CONCLUSION: Use of IVF is a strong confounder
      because it is associated with both use of folic acid and twinning. Even when
      misclassification of IVF was reduced to 5%, this bias persisted in the adjusted
      model. Using a 40% misclassified surrogate to adjust for IVF, as reported in the
      Swedish study, probably led to a false finding that folic acid increased
      dizygotic twinning.

PMID- 15722371
TI  - Identifying regulatory subnetworks for a set of genes.
AB  - High throughput genomic/proteomic strategies, such as microarray studies, drug
      screens, and genetic screens, often produce a list of genes that are believed to
      be important for one or more reasons. Unfortunately it is often difficult to
      discern meaningful biological relationships from such lists. This study presents
      a new bioinformatic approach that can be used to identify regulatory subnetworks
      for lists of significant genes or proteins. We demonstrate the utility of this
      approach using an interaction network for yeast constructed from BIND, TRANSFAC,
      SCPD, and chromatin immunoprecipitation (ChIP)-Chip data bases and lists of genes
      from well known metabolic pathways or differential expression experiments. The
      approach accurately rediscovers known regulatory elements of the heat shock
      response as well as the gluconeogenesis, galactose, glycolysis, and glucose
      fermentation pathways in yeast. We also find evidence supporting a previous
      conjecture that approximately half of the enzymes in a metabolic pathway are
      transcriptionally co-regulated. Finally we demonstrate a previously unknown
      connection between GAL80 and the diauxic shift in yeast.

PMID- 15722372
TI  - Active kinase proteome screening reveals novel signal complexity in
      cardiomyopathy.
AB  - Recent advances in the characterization of the phosphoproteome have been limited
      to measuring phosphorylation statuses, which imply but do not measure protein
      kinase activity directly. As such, the ability to screen, compare, and define
      multiple protein enzymatic activities across divergent samples remains a daunting
      challenge in proteomics. Here, we describe a gel-based kinase assay coupled to MS
      identification as an approach to map global kinase activity and assign pathway
      architecture to specified biologic contexts. We demonstrate the utility of this
      method as a platform for the comparison of proteomes based on differences in both
      kinase activities and for use in the de novo substrate identification for
      individual kinases. This approach allowed us to map the signal perturbations in
      the post-natal heart that were associated with activation of a myopathic cascade
      as mediated by the mitogen-activated protein kinase MKK6 and established the
      novel observation that MKK6 promotes the development of cardiomyopathy through
      multiple substrate interactions.

PMID- 15722373
TI  - ESTviewer: a web interface for visualizing mouse, rat, cattle, pig and chicken
      conserved ESTs in human genes and human alternatively spliced variants.
AB  - ESTviewer is a web application for interactively visualizing human gene
      structures, with emphasis on mammalian and avian expressed sequence tags (ESTs)
      that are conserved in the human genome and alternatively spliced (AS) variants.
      AS variants from the UCSC, Vega and PSEP annotations are presented in this
      application for comparison. EST data from six species, human, mouse, rat, cattle,
      pig and chicken, are mapped to the human genome to show cross-species EST
      conservation in annotated exonic and intronic regions. Cross-species EST
      conservation is evolutionarily and functionally important because it represents
      the effects of selection pressure on genic regions and transcriptome over
      evolutionary time. Emphatically, ESTviewer provides a convenient tool to compare
      highly conserved non-human ESTs and human AS variants. The application takes
      human gene accession Ids or coordinates of genomic sequences as inputs and
      presents annotated gene structures and their AS variants. In addition, the
      lengths and percentages of human genic regions covered by ESTs are displayed to
      show the level of EST coverage of different species. The percentages of the UCSC,
      Vega and PSEP annotated exons covered by ESTs of the six studied species are also
      displayed in the interface.

PMID- 15722375
TI  - Sorting points into neighborhoods (SPIN): data analysis and visualization by
      ordering distance matrices.
AB  - SUMMARY: We introduce a novel unsupervised approach for the organization and
      visualization of multidimensional data. At the heart of the method is a
      presentation of the full pairwise distance matrix of the data points, viewed in
      pseudocolor. The ordering of points is iteratively permuted in search of a linear
      ordering, which can be used to study embedded shapes. Several examples indicate
      how the shapes of certain structures in the data (elongated, circular and
      compact) manifest themselves visually in our permuted distance matrix. It is
      important to identify the elongated objects since they are often associated with
      a set of hidden variables, underlying continuous variation in the data. The
      problem of determining an optimal linear ordering is shown to be NP-Complete, and
      therefore an iterative search algorithm with O(n3) step-complexity is suggested.
      By using sorting points into neighborhoods, i.e. SPIN to analyze colon cancer
      expression data we were able to address the serious problem of sample
      heterogeneity, which hinders identification of metastasis related genes in our
      data. Our methodology brings to light the continuous variation of heterogeneity-
      starting with homogeneous tumor samples and gradually increasing the amount of
      another tissue. Ordering the samples according to their degree of contamination
      by unrelated tissue allows the separation of genes associated with irrelevant
      contamination from those related to cancer progression. AVAILABILITY: Software
      package will be available for academic users upon request.

PMID- 15722374
TI  - Recoverable one-dimensional encoding of three-dimensional protein structures.
AB  - One-dimensional (1D) structures of proteins such as secondary structure and
      contact number provide intuitive pictures to understand how the native three
      dimensional (3D) structure of a protein is encoded in the amino acid sequence.
      However, it is still not clear whether a given set of 1D structures contains
      sufficient information for recovering the underlying 3D structure. Here we show
      that the 3D structure of a protein can be recovered from a set of three types of
      1D structures, namely, secondary structure, contact number and residue-wise
      contact order which is introduced here for the first time. Using simulated
      annealing molecular dynamics simulations, the structures satisfying the given
      native 1D structural restraints were sought for 16 proteins of various structural
      classes and of sizes ranging from 56 to 146 residues. By selecting the structures
      best satisfying the restraints, all the proteins showed a coordinate RMS
      deviation of <4 A from the native structure, and, for most of them, the deviation
      was even <2 A. The present result opens a new possibility to protein structure
      prediction and our understanding of the sequence-structure relationship.

PMID- 15722376
TI  - MtbRegList, a database dedicated to the analysis of transcriptional regulation in
      Mycobacterium tuberculosis.
AB  - MtbRegList is a database dedicated to the analysis of gene expression and
      regulation data in Mycobacterium tuberculosis. It is designed to contain
      predicted and characterized regulatory DNA motifs cross-referenced with
      corresponding transcription factor(s), and experimentally identified
      transcription start sites. MtbRegList can also handle flexible and complex
      genomic search requests, besides having a noteworthy browsing capability.
      AVAILABILITY: MtbRegList is freely available at
      http://www.USherbrooke.ca/vers/MtbRegList

PMID- 15722377
TI  - Partial SP-B deficiency perturbs lung function and causes air space
      abnormalities.
AB  - Surfactant protein B (SP-B) is required for function of newborn and adult lung,
      and partial deficiency has been associated with susceptibility to lung injury. In
      the present study, transgenic mice were produced in which expression of SP-B in
      type II epithelial cells was conditionally regulated. Concentrations of SP-B were
      maintained at 60-70% of that normally present in control. Immunostaining for SP-B
      demonstrated cellular heterogeneity in expression of the protein. In subsets of
      type II cells in which SP-B staining was decreased, immunostaining for pro-SP-C
      was increased and lamellar body ultrastructure was disrupted, consistent with
      focal SP-B deficiency. Fluorescence-activated cell sorting analyses of freshly
      isolated type II cells identified a population of cells with low SP-B content and
      a smaller population with increased SP-B content, confirming nonuniform
      expression of the SP-B transgene. Focal air space enlargement, without cellular
      infiltration or inflammation, was observed. Pressure-volume curves indicated that
      maximal tidal volume was unchanged; however, hysteresis was modestly altered and
      residual volumes were significantly decreased in the SP-B-deficient mice.
      Chronic, nonuniform SP-B deficiency perturbed pulmonary function and caused air
      space enlargement.

PMID- 15722378
TI  - Difference in proangiogenic potential of systemic and pulmonary endothelium: role
      of CXCR2.
AB  - The systemic vasculature in and surrounding the lung is proangiogenic, whereas
      the pulmonary vasculature rarely participates in neovascularization. We studied
      the effects of the proangiogenic ELR+ CXC chemokine MIP-2 (macrophage
      inflammatory protein-2) on endothelial cell proliferation and chemotaxis. Mouse
      aortic, pulmonary arterial, and lung microvascular endothelial cells were
      isolated and subcultured. Proliferation ([3H]thymidine uptake) and migration
      (Transwell chemotaxis) were evaluated in each cell type at baseline and upon
      exposure to MIP-2 (1-100 ng/ml) without and with exposure to hypoxia (24 h)
      reoxygenation. Baseline proliferation did not vary among cell types, and all
      cells showed increased proliferation after MIP-2. Aortic cell chemotaxis
      increased markedly upon exposure to MIP-2; however, neither pulmonary artery nor
      lung microvascular endothelial cells responded to this chemokine. Assessment of
      CXCR2, the G protein-coupled receptor through which MIP-2 signals, displayed no
      baseline difference in mRNA, protein, or cell surface expression among cell
      types. Exposure to hypoxia increased expression of CXCR2 of aortic endothelial
      cells only. Additionally, aortic cells, compared with pulmonary cells, showed
      significantly greater protein and activity of cathepsin S, a proteolytic enzyme
      important for cell motility. Thus the combined effects of increased cathepsin S
      activity, providing increased motility and enhanced CXCR2 expression after
      hypoxia, both contribute to the proangiogenic phenotype of systemic arterial
      endothelial cells.

PMID- 15722379
TI  - A role for platelet-derived growth factor beta-receptor in a newborn rat model of
      endothelin-mediated pulmonary vascular remodeling.
AB  - Newborn rats exposed to 60% O2 for 14 days develop endothelin (ET)-1-dependent
      pulmonary hypertension with vascular remodeling, characterized by increased
      smooth muscle cell (SMC) proliferation and medial thickening of pulmonary
      resistance arteries. Using immunohistochemistry and Western blot analyses, we
      examined the effect of exposure to 60% O2 on expression in the lung of receptors
      for the platelet-derived growth factors (PDGF), which are implicated in the
      pathogenesis of arterial smooth muscle hyperplasia. We observed a marked O2
      induced upregulation of PDGF-alpha and -beta receptors (PDGF-alphaR and -betaR)
      on arterial smooth muscle. This led us to examine pulmonary vascular PDGF
      receptor expression in 60% O2-exposed rats given SB-217242, a combined ET
      receptor antagonist, which we found prevented the O2-induced upregulation of PDGF
      betaR, but not PDGF-alphaR, on arterial smooth muscle. PDGF-BB, a major PDGF
      betaR ligand, was found to be a potent in vitro inducer of hyperplasia and DNA
      synthesis in cultured pulmonary artery SMC from infant rats. A critical role for
      PDGF-betaR ligands in arterial SMC proliferation was confirmed in vivo using a
      truncated soluble PDGF-betaR intervention, which attenuated SMC proliferation
      induced by exposure to 60% O2. Collectively, these data are consistent with a
      major role for PDGF-betaR-mediated SMC proliferation, acting downstream of
      increased ET-1 in a newborn rat model of 60% O2-induced pulmonary hypertension.

PMID- 15722380
TI  - Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated
      Ca2+ and nonselective cation channels.
AB  - Previous studies indicated that acute hypoxia increased intracellular Ca(2+)
      concentration ([Ca(2+)](i)), Ca(2+) influx, and capacitative Ca(2+) entry (CCE)
      through store-operated Ca(2+) channels (SOCC) in smooth muscle cells from distal
      pulmonary arteries (PASMC), which are thought to be a major locus of hypoxic
      pulmonary vasoconstriction (HPV). Moreover, these effects were blocked by Ca(2+)
      free conditions and antagonists of SOCC and nonselective cation channels (NSCC).
      To test the hypothesis that in vivo HPV requires CCE, we measured the effects of
      SOCC/NSCC antagonists (SKF-96365, NiCl(2), and LaCl(3)) on pulmonary arterial
      pressor responses to 2% O(2) and high-KCl concentrations in isolated rat lungs.
      At concentrations that blocked CCE and [Ca(2+)](i) responses to hypoxia in PASMC,
      SKF-96365 and NiCl(2) prevented and reversed HPV but did not alter pressor
      responses to KCl. At 10 microM, LaCl(3) had similar effects, but higher
      concentrations (30 and 100 microM) caused vasoconstriction during normoxia and
      potentiated HPV, indicating actions other than SOCC blockade. Ca(2+)-free
      perfusate and the voltage-operated Ca(2+) channel (VOCC) antagonist nifedipine
      were potent inhibitors of pressor responses to both hypoxia and KCl. We conclude
      that HPV required influx of Ca(2+) through both SOCC and VOCC. This dual
      requirement and virtual abolition of HPV by either SOCC or VOCC antagonists
      suggests that neither channel provided enough Ca(2+) on its own to trigger PASMC
      contraction and/or that during hypoxia, SOCC-dependent depolarization caused
      secondary activation of VOCC.

PMID- 15722381
TI  - Post-dural puncture headache in young adults: comparison of two small-gauge
      spinal catheters with different needle design.
AB  - BACKGROUND: To reduce the risk of post-dural puncture headache (PDPH) in
      continuous spinal anaesthesia, small-gauge spinal catheter systems with different
      techniques of dural perforation have been developed. METHODS: Two systems, the
      catheter through-needle technique (MicroCatheter, Portex, UK) and the catheter
      over-needle technique (22G Spinocath, B. Braun, Germany), were used in 18 young
      healthy volunteers (age 18-30 yr), who were enrolled in a neuroendocrinological
      investigation for analysis of neuropeptides in cerebrospinal fluid (CSF). After
      intermittent sampling of CSF (17 x 0.5 ml over 4 h), the catheter was removed and
      the development of PDPH and pain intensity were documented prospectively by the
      subjects in a standardized headache assessment (11-point numerical rating scale
      [NRS]). RESULTS: The study revealed a high overall incidence of PDPH (78%) with
      no significant differences between groups (P=0.26). However, the over-needle
      group showed a significantly shorter duration of PDPH (2.4 [SD 2.3] vs 5.1 [3.1]
      days, P=0.050) and lower maximum pain intensity (3.1 [2.9] vs 7.3 [3.4] NRS,
      P=0.014) than the through-needle group. CONCLUSIONS: The results demonstrate a
      potential benefit of the catheter over-needle technique for the reduction of the
      duration and intensity of PDPH.

PMID- 15722382
TI  - Characterization and comparison of recombinant human and rat TRPV1 receptors:
      effects of exo- and endocannabinoids.
AB  - BACKGROUND: TRPV1 is a ligand-gated ion channel whose activation by capsaicin
      increases intracellular Ca(2+) ([Ca(2+)](i)). TRPV1 and cannabinoid CB(1)
      receptor activation are capable of eliciting analgesia. In this study, using
      recombinant human (h) and rat (r) TRPV1 receptors expressed in HEK293 cells, we
      have performed a comparison of both TRPV1 species at 22 and 37 degrees C and
      compared endo- and exocannabinoid activity at both receptors. METHODS:
      [Ca(2+)](i) was measured in Fura-2-loaded HEK293(hTRPV1) and HEK293(rTRPV1)
      cells. To assess native CB(1) receptor activity, [(35)S]GTPgammaS binding to
      membranes prepared from rat cerebellum was measured. RESULTS: Both capsaicin
      (pEC(50) rat approximately 6.9 and pEC(50) human approximately 6.8 at 37 degrees
      C) and anandamide (pEC(50) rat approximately 5.3 and pEC(50) human approximately
      5.8 at 37 degrees C) produced a concentration-dependent increase in [Ca(2+)](i)
      in rat and human systems and at 22 and 37 degrees C. In HEK293(rTRPV1) cells,
      anandamide appeared to be a partial agonist. Capsazepine demonstrated competitive
      antagonism at both human and rat TRPV1 receptors and at both temperatures
      studied. Capsazepine effects were not temperature dependent: pK(B) at rTRPV1 was
      5.98 at 22 degrees C and 6.02 at 37 degrees C, and pK(B) at hTRPV1 was 6.76 at 22
      degrees C and 6.75 at 37 degrees C. However, there was a consistent 6-fold
      increase in capsazepine potency for hTRPV1 relative to rTRPV1. The exocannabinoid
      Delta(9)-tetrahydrocannabinol failed to increase [Ca(2+)](i), although its
      solvent ethanol was an effective TRPV1 activator. In the [(35)S]GTPgammaS binding
      assay using rat cerebellar membranes, anandamide (pEC(50) approximately 5.8) and
      Delta(9)-tetrahydrocannabinol (pEC(50) approximately 7.1), but not capsaicin,
      stimulated binding. Delta(9)-tetrahydrocannabinol was a partial agonist. pEC(50)
      values for anandamide at rTRPV1 and rCB(1) were similar. CONCLUSIONS: There were
      small differences in the pharmacology of rat and human TRPV1 receptors. Whilst
      capsaicin activated TRPV1 and Delta(9)-tetrahydrocannabinol activated CB(1),
      anandamide is an endogenous agonist for both receptor systems.

PMID- 15722383
TI  - Recovery of N100 component of auditory event-related potentials and EEG after
      cardiac arrest during propofol sedation.
AB  - We report on the EEG monitoring of a patient who suffered an episode of
      postoperative ventricular fibrillation (VF) following coronary artery bypass
      grafting (CABG). VF initially caused a considerable suppression and slowing of
      the EEG. The recovery of cerebral function was evaluated by recording both EEG
      and auditory event related potentials (ERPs). Six hours after the episode of VF,
      when the patient was asleep but arousable to voice command, the N100 component of
      the auditory ERPs had recovered to the level measured before the operation,
      whereas the EEG was still very slow for that level of sedation. This may have
      been due to VF having less effect on the N100 component than on the background
      EEG. Our findings suggest that measuring evoked potentials may improve the
      evaluation of brain function after cardiac arrest.

PMID- 15722384
TI  - Vasoactive characteristics of bupivacaine and levobupivacaine with and without
      adjuvant epinephrine in peripheral human skin.
AB  - BACKGROUND: Epinephrine is added to local anaesthetic preparations to prolong
      their action and reduce their systemic absorption. Bupivacaine and
      levobupivacaine cause vasodilatation at clinical doses, but lower doses appear to
      cause vasoconstriction. The aim of this study was to characterize fully the
      vasoactive effects of these anaesthetics, using an objective measure of blood
      flow, and to assess the influence of adding epinephrine. METHODS: Laser Doppler
      imaging was used to measure the forearm skin blood flow responses to intradermal
      injection of eight doses of bupivacaine and levobupivacaine in 10 healthy male
      volunteers. The doses tested ranged from 0.008% to 0.75%, and the five highest
      doses were administered both with and without adjuvant epinephrine 2.5 microg ml(
      1). RESULTS: The cumulative responses to the lower subclinical concentrations
      (0.008-0.0625%) of both anaesthetics were smaller than or similar to that
      produced by saline alone, indicating a net vasoconstrictive effect. Higher doses
      caused net vasodilatation, and the levobupivacaine responses were generally lower
      than the corresponding bupivacaine responses (P=0.022). Epinephrine 2.5 microg
      ml(-1) significantly reduced the responses to clinical doses of both drugs
      (P<0.001), producing net vasoconstriction. CONCLUSIONS: Bupivacaine and
      levobupivacaine have a biphasic vascular effect when injected intradermally, with
      subclinical doses causing net vasoconstriction. The addition of epinephrine 2.5
      microg ml(-1) decreases these responses markedly.

PMID- 15722385
TI  - Potential value of adenosine 5'-triphosphate (ATP) and adenosine in anaesthesia
      and intensive care medicine.
AB  - Extracellular adenosine and adenosine triphosphate (ATP) are involved in
      biological processes including neurotransmission, muscle contraction, cardiac
      function, platelet function, vasodilatation, signal transduction and secretion in
      a variety of cell types. They are released from the cytoplasm of several cell
      types and interact with specific purinergic receptors which are present on the
      surface of many cells. This review summarizes the evidence on the potential value
      and applicability of ATP (not restricted to ATP-MgCl(2)) and adenosine in the
      field of anaesthesia and intensive care medicine. It focuses, in particular, on
      evidence and roles in treatment of acute and chronic pain and in sepsis. Based on
      the evidence from animal and clinical studies performed during the last 20 years,
      ATP could provide a valuable addition to the therapeutic options in anaesthesia
      and intensive care medicine. It may have particular roles in pain management,
      modulation of haemodynamics and treatment of shock.

PMID- 15722386
TI  - Baroreflex control of heart rate during and after propofol infusion in humans.
AB  - BACKGROUND: This study was designed to determine cardiovagal baroreflex gain
      during propofol infusion and to characterize its recovery profile using the
      pharmacological and spontaneous sequence methods in 13 healthy volunteers without
      cardiovascular or autonomic disorders. METHODS: After an 8- to 10-h fast and no
      premedication, measurements of RR intervals obtained from the electrocardiogram
      and non-invasive beat-to-beat systolic blood pressure (SP) were made at conscious
      baseline, at 60 and 120 min after induction of general anaesthesia using
      propofol, and at 20, 60, 120 and 180 min after emergence from anaesthesia. During
      propofol anaesthesia, ventilation was mechanically controlled to maintain
      normocapnia and calculated propofol concentration was adjusted by a TCI system at
      5 microg ml(-1). Baroreflex responses were triggered by bolus i.v. injections of
      phenylephrine and nitroprusside to alter SP by 15-30 mm Hg. The linear portions
      of the baroreflex curves relating RR intervals and SP by least-square regression
      analysis were determined to obtain pharmacological gains. In addition,
      spontaneous sequence baroreflex gains were calculated from spontaneously
      fluctuating SP and RR intervals. RESULTS: Baseline pressor and depressor test
      gains before propofol anaesthesia were 29.1 (SD 14.9) and 12.5 (7.8) ms mm Hg(
      1), respectively. They were significantly depressed by 65-73% during propofol
      infusions. Similarly, baseline up- and down-sequence baroreflex gains were 33.8
      (28.9) and 27.3 (19.8) ms mm Hg(-1), respectively, and were significantly
      depressed by 71-87% during propofol anaesthesia. Pressor test and up-sequence
      baroreflex gains returned to the baseline values 20 min after emergence from
      propofol anaesthesia, but depressor test and down-sequence baroreflex gains did
      not recover until 60 min after emergence. CONCLUSIONS: We conclude that heart
      rate responses to both lowering and elevating blood pressure were depressed by
      propofol anaesthesia, and 60 min was required for their full recovery after
      discontinuation of propofol infusion.

PMID- 15722387
TI  - Effect of partial liquid ventilation and nebulized perfluorocarbon on CT lung
      density distribution: randomized controlled study of experimental lung injury.
AB  - BACKGROUND: Perfluorocarbon (PFC) liquid can improve gas exchange in acute lung
      injury. How PFC aerosol is distributed in the lung is unknown. METHODS: We
      induced lung injury in rabbits with saline lavage, followed by mechanical
      ventilation in the supine position. The animals were divided into three groups: a
      control group, a group treated with partial liquid ventilation and a group given
      nebulized perfluorocarbon (PF 5080). We made CT image slices of the excised
      lungs. In the apical, middle and caudal slices we defined three regions of
      interest, from anterior to posterior, and noted the mean attenuation of each
      area. We also studied two rabbits which had not received lung injury or
      mechanical ventilation. RESULTS: Group means were different between the normal
      rabbits and all three study groups. There was a difference between the control
      and partial liquid ventilation groups, and between the partial liquid ventilation
      and nebulized groups, but no difference between the nebulized and control groups.
      Within each treatment group, there was no regional difference in the distribution
      of density. CONCLUSIONS: PF 5080 is not deposited in large amounts by aerosol.
      Less PFC was found in the lungs after partial liquid ventilation than expected.
      Within treatment groups, lung densities indicate less gravitational and regional
      differences than found in other studies.

PMID- 15722388
TI  - Boosted saquinavir hard gel formulation exposure in HIV-infected subjects:
      ritonavir 100 mg once daily versus twice daily.
AB  - OBJECTIVES: The amount of ritonavir needed to enhance saquinavir hard gel (hg)
      plasma concentrations is unclear. Reduced ritonavir dosing may help to reduce
      ritonavir-related side effects and costs. This study examined the
      pharmacokinetics of twice-daily saquinavir-hg (1000 mg) in the presence of
      ritonavir 100 mg, dosed twice-daily and once-daily on one single occasion.
      METHODS: Eighteen HIV-infected adults taking saquinavir/ritonavir 1000/100 mg
      twice-daily underwent pharmacokinetic (PK) assessment of saquinavir/ritonavir on
      day 1 following a morning saquinavir/ritonavir dose. On day 2, PK assessment was
      repeated when subjects took saquinavir without ritonavir. Drug intake (with a
      standard meal containing 20 g of fat) was timed on days -1, 1 and 2. Geometric
      mean ratios (GMR) and 95% confidence intervals (CI) were calculated to assess
      changes in saquinavir PK parameters. RESULTS: Geometric mean saquinavir AUC(0
      12), C(trough), C(max) and elimination half-life on days 1 and 2 were 14 389 and
      9590 ng.h/mL, 331 and 234 ng/mL, 2503 and 1893 ng/mL and 2.80 and 2.82 h,
      respectively. The GMR (95% CI) for these parameters were 0.67 (0.53-0.84), 0.71
      (0.48-1.04), 0.76 (0.58-0.98) and 1.01 (0.86-1.18), respectively. CONCLUSIONS:
      Withholding a ritonavir dose significantly reduces overall saquinavir exposure
      and C(max), but had no impact on the elimination half-life. These data establish
      the need to administer saquinavir and ritonavir simultaneously.

PMID- 15722389
TI  - Antiretroviral adherence, drug resistance, viral fitness and HIV disease
      progression: a tangled web is woven.
AB  - The clinical goals of HIV treatment are optimally accomplished through consistent
      high-level adherence to highly active antiretroviral therapy (HAART) and durable
      suppression of the viral load. However, as a result of the need for lifelong
      therapy and HIV's prodigious replication rate and error-prone reverse
      transcriptase, varying amounts of antiretroviral drug resistance are common in
      treated individuals. Medication adherence is linked to the development of drug
      resistance, although not by a simple linear relationship. Recent studies have
      suggested that extensive drug resistance is not a major determinant of HIV
      disease progression and death. Rather, failure to access care and discontinuation
      of or non-adherence with therapy are arguably the most important factors
      associated with HIV disease progression in the HAART era. Other data indicate
      that continued therapy in the setting of extensive drug resistance and the
      inability to achieve viral suppression can provide continued clinical benefit.
      Such benefit may be mediated, at least partially, by reductions in viral fitness
      associated with drug resistance mutations.

PMID- 15722390
TI  - Daptomycin tested against 915 bloodstream isolates of viridans group streptococci
      (eight species) and Streptococcus bovis.
AB  - OBJECTIVES: To evaluate the activity of daptomycin tested against numerous
      species of viridans group streptococci and Streptococcus bovis, which are
      associated with wound infections, sepsis, cellulitis, endocarditis, abscesses and
      dental caries. The incidence of penicillin-resistant (non-susceptible) and MLS(B)
      resistant strains among viridans group streptococci often varies by species.
      METHODS: The activity of daptomycin was compared with seven other antimicrobial
      classes using reference broth microdilution and disc diffusion methods tested
      against 915 bacteraemic isolates of streptococci (815 viridans group strains; 100
      S. bovis). RESULTS: Among all species of viridans group streptococci and S.
      bovis, 99.9% of isolates were susceptible to daptomycin (MIC values, < or = 0.016
      2 mg/L). In contrast, penicillin, erythromycin and tetracycline susceptibility
      varied widely between species. Erythromycin susceptibility was in the range 48.6
      88.7%, penicillin susceptibility in the range 65.5-98.1% and tetracycline in the
      range 35.0-93.9%. The inter-method agreement between daptomycin and linezolid
      resistance (comparison agent) disc diffusion and broth microdilution test results
      was high, each showing near complete susceptibility (99.9%). CONCLUSIONS:
      Daptomycin is an active antimicrobial agent that has a usable potency against
      eight species of viridans group streptococci, as well as S. bovis, with all MIC
      values at < or =2 mg/L.

PMID- 15722391
TI  - Bacteriostatic and bactericidal activities of eight fluoroquinolones against
      MexAB-OprM-overproducing clinical strains of Pseudomonas aeruginosa.
AB  - OBJECTIVES: To assess the impact of stable overproduction of efflux system MexAB
      OprM on the bacteriostatic and bactericidal activities of fluoroquinolones
      against clinical Pseudomonas aeruginosa strains. METHODS: The minimal inhibitory
      concentrations (MICs) and the minimal bactericidal concentrations (MBCs) of eight
      fluoroquinolones (pefloxacin, norfloxacin, ofloxacin, moxifloxacin, levofloxacin,
      ciprofloxacin, trovafloxacin and grepafloxacin) were determined for nine post
      therapy resistant isolates of P. aeruginosa overexpressing MexAB-OprM. Clinical
      significance of low-level resistance conferred by the efflux mechanism was
      evaluated with a Monte Carlo simulation. RESULTS: Compared with their pre-therapy
      susceptible counterparts, seven out of the nine post-therapy efflux mutants
      exhibited a modest two- to eight-fold increase in resistance to all the
      fluoroquinolones tested. Interestingly, stronger variations in resistance (up to
      64-fold) were observed in two other mutants, one of which had acquired a GyrB
      target mutation in addition to efflux under chemotherapy. Time-kill experiments
      showed that MexAB-OprM up-regulation did not confer tolerance to fluoroquinolones
      as the ratio of MBC to MIC was less than 4 for most of the strains. To gain an
      insight into the clinical significance of resistance conferred by MexAB-OprM, a
      Monte Carlo simulation was conducted with various fluoroquinolone regimens. With
      this model, low levels of resistance to ciprofloxacin (MIC > or = 0.25 mg/L) or
      levofloxacin (MIC > or = 1 mg/L), such as those due to overproduced MexAB-OprM,
      were predicted to result in poor clinical outcomes. CONCLUSIONS: Altogether,
      these data strongly suggest that when derepressed, MexAB-OprM provides P.
      aeruginosa with a resistance that may be sufficient to impair the efficacy of
      single therapy with highly potent fluoroquinolones, such as ciprofloxacin and
      ofloxacin.

PMID- 15722392
TI  - Empirical antibiotics against Gram-positive infections for febrile neutropenia:
      systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: To assess the value of empirical anti-Gram-positive antibiotics for
      the treatment of febrile neutropenia. METHODS: Systematic review and meta
      analysis of randomized controlled trials comparing antibiotics with anti-Gram
      positive spectrum to control or placebo, in addition to the same baseline
      antibiotic regimen in both arms. We searched MEDLINE, EMBASE, LILACS, the
      Cochrane Library, conference proceedings, and references. No restrictions on
      inclusion were imposed. Two reviewers independently applied selection criteria,
      carried out quality assessment, and extracted the data. Relative risks with 95%
      confidence intervals were pooled using the fixed effect model. The primary
      outcome assessed was all-cause mortality. RESULTS: Thirteen studies met inclusion
      criteria, including 2392 participants. Glycopeptides were assessed in nine
      trials. Empirical anti-Gram-positive antibiotics were assessed for the initial
      treatment in 11 studies, and for persistent fever in two. No significant
      difference in all-cause mortality was seen [RR 0.86 (0.58-1.26), seven studies,
      852 participants]. Overall failure at end of therapy occurred equally [RR 1.00
      (0.79-1.27), six studies, 943 participants]. Failure associated with treatment
      modifications was more frequent in the control arm when empirical initial
      glycopeptides were assessed [RR 0.70 (0.61-0.80), five studies, 1178
      participants]. Bacterial superinfections, mainly Gram-positive, were detected
      less frequently in the intervention arm. Adverse events were significantly more
      common with the additional antibiotic, and nephrotoxicity was significantly more
      common with additional glycopeptides [RR 1.88 (1.10-3.22), six studies, 1282
      participants]. No significant heterogeneity was present in these comparisons.
      CONCLUSIONS: The use of glycopeptides can be safely deferred until the
      documentation of a resistant Gram-positive infection.

PMID- 15722393
TI  - Resistance to ceftazidime is associated with a S220Y substitution in the omega
      loop of the AmpC beta-lactamase of a Serratia marcescens clinical isolate.
AB  - OBJECTIVES: The aim of this study was to characterize the ampC beta-lactamase
      gene of a clinical isolate of Serratia marcescens resistant to ceftazidime.
      METHODS: S. marcescens SMSA was isolated from an intra-abdominal wound of a
      patient previously treated with ceftazidime. A susceptible strain, SLS73, was
      used as a control. Susceptibility testing, PCR, DNA sequencing, molecular
      cloning, site-directed mutagenesis and determination of kinetic parameters were
      carried out to investigate the mechanism of resistance to ceftazidime. RESULTS:
      MICs of ceftazidime were 64 and 0.2 mg/L for SMSA and SLS73, respectively.
      Sequencing of the ampC gene of SMSA was carried out. When compared with the
      closest AmpC enzyme, the S. marcescens S3 beta-lactamase, the novel protein
      showed E57Q, Q129K and S220Y substitutions. The S220Y substitution is located in
      the omega loop. Introduced by mutagenesis in the ampC gene of SLS73, this
      substitution conferred the same level of resistance to ceftazidime. The catalytic
      efficiency (k(cat)/K(m)) of the mutated enzyme toward ceftazidime was increased
      by about 100-fold. CONCLUSIONS: We present another example of in vivo selection
      of broad-spectrum resistance by amino acid substitution in the omega loop of
      chromosomal AmpC beta-lactamase in S. marcescens.

PMID- 15722394
TI  - Evaluation of different methods for detecting methicillin (oxacillin) resistance
      in Staphylococcus aureus.
AB  - OBJECTIVES: To evaluate the performance of oxacillin, cefazolin, cefoxitin,
      cefotaxime and imipenem discs; Etest for oxacillin; microdilution; agar screening
      plates with 2 and 6 mg/L of oxacillin; and PBP2' agglutination for detection of
      methicillin-resistant Staphylococcus aureus (MRSA). METHODS: A total of 102
      clinical S. aureus isolates, including 51 MRSA isolates, tested by PCR for the
      presence or absence of the mecA gene (gold standard method), isolated from
      different patients and at different times, were tested with: oxacillin (1
      microg), cefazolin, cefoxitin, cefotaxime and imipenem (all 30 microg) discs;
      Etest for oxacillin; microdilution with oxacillin; agar screening tests (ORSAB
      medium) with 2 mg/L or 6 mg/L of oxacillin; and PBP2' agglutination with two
      different kits for detection of MRSA strains. RESULTS: The cefoxitin disc, ORSAB
      medium and PBP2' detection all showed 100% sensitivity. The cefoxitin, cefazolin
      and imipenem discs, Etest for oxacillin, microdilution and agar screening method
      with 6 mg/L at 24 h showed the highest specificity (100%), although variable
      degrees of sensitivity. The cefoxitin disc, which showed negative and positive
      predictive values of 100% and 98%, respectively was the best method for detecting
      MRSA isolates. CONCLUSIONS: In the absence of availability of molecular biology
      techniques, the cefoxitin disc was the best predictor of methicillin resistance
      in S. aureus from among the techniques tested.

PMID- 15722395
TI  - Comparison of multidrug resistance gene regions between two geographically
      unrelated Salmonella serotypes.
AB  - OBJECTIVES: The aim of this study was to identify chromosomally integrated genes
      conferring multidrug resistance to a Salmonella enterica (S.) serotype
      Typhimurium isolate, phage type DT193, isolated in Ireland and to compare them
      with resistance genes conferring plasmid-mediated multidrug resistance to a S.
      Enteritidis isolate from Italy. METHODS: A complete DNA sequence of the regions
      containing the resistance genes was obtained from the chromosome of the S.
      Typhimurium DT193 isolate and from the IncI plasmid of the S. Enteritidis
      isolate. The plasmid was also characterized by conjugation and incompatibility
      grouping. RESULTS: Two 10 kb multidrug resistance non-Salmonella Genomic Island 1
      type clusters were independently identified in the S. Enteritidis plasmid and in
      the chromosome of the S. Typhimurium isolate. Detailed characterization
      identified an IP-type 2 integron containing a dfrA1-aadA1 gene cassette and other
      common resistance determinants derived from the RSF1010 plasmid. CONCLUSIONS:
      These multidrug resistance regions originate following chromosomal integration of
      key resistance markers encountered on plasmids circulating in other Salmonella
      serotypes. This mechanism of marker acquisition may have future implications for
      the evolution of similar structures in previously susceptible serotypes, leading
      to an increased public health risk.

PMID- 15722396
TI  - Antistaphylococcal activity of the novel cephalosporin CB-181963 (CAB-175).
AB  - OBJECTIVES: We examined the antistaphylococcal activity of the novel
      cephalosporin CB-181963 (formerly known as CAB-175), with emphasis on its
      microbiological activity and penicillin-binding protein specificities. METHODS:
      Using established procedures, we examined the activity of CB-181963 against
      methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains of
      Staphylococcus aureus in both planktonic and biofilm culture. We also determined
      whether CB-181963 exhibited a post-antibiotic effect (PAE). A radioactive
      competition assay with (3)H-labelled benzylpenicillin was used to determine
      penicillin-binding protein (PBP) affinities of CB-181963, including binding to
      PBP2a from MRSA. The potential for emergence of CB-181963-resistant mutants in
      MSSA and MRSA strains was examined using plating procedures. RESULTS: CB-181963
      showed excellent activity against MRSA strains resistant to other cephalosporins
      in both planktonic and biofilm cultures. However, in common with other
      cephalosporins it was unable to eradicate biofilms. CB-181963 had a short PAE
      compared with other beta-lactam antibiotics. CB-181963 retained activity against
      a strain expressing type A beta-lactamase and demonstrated affinity for PBP2a of
      MRSA. Mutants resistant to CB-181963 were not recovered in either MSSA or MRSA.
      CONCLUSIONS: CB-181963 is a potent antistaphylococcal agent with better activity
      against MRSA than other cephalosporins. The anti-MRSA activity is correlated with
      elevated binding to PBP2a. CB-181963 may have a role in the treatment of
      staphylococcal infections, including those caused by MRSA and in the prophylaxis
      of biofilm-associated MSSA and MRSA infections. However, because of its short
      PAE, CB-181963 may have to be administered more frequently than other beta-lactam
      antibiotics, or given via prolonged infusion.

PMID- 15722397
TI  - The 'number needed to sample' in primary care research. Comparison of two primary
      care sampling frames for chronic back pain.
AB  - BACKGROUND: Sampling for primary care research must strike a balance between
      efficiency and external validity. For most conditions, even a large population
      sample will yield a small number of cases, yet other sampling techniques risk
      problems with extrapolation of findings. OBJECTIVE: To compare the efficiency and
      external validity of two sampling methods for both an intervention study and
      epidemiological research in primary care--a convenience sample and a general
      population sample--comparing the response and follow-up rates, the demographic
      and clinical characteristics of each sample, and calculating the 'number needed
      to sample' (NNS) for a hypothetical randomized controlled trial. METHODS: In
      1996, we selected two random samples of adults from 29 general practices in
      Grampian, for an epidemiological study of chronic pain. One sample of 4175 was
      identified by an electronic questionnaire that listed patients receiving regular
      analgesic prescriptions--the 'repeat prescription sample'. The other sample of
      5036 was identified from all patients on practice lists--the 'general population
      sample'. Questionnaires, including demographic, pain and general health measures,
      were sent to all. A similar follow-up questionnaire was sent in 2000 to all those
      agreeing to participate in further research. We identified a potential group of
      subjects for a hypothetical trial in primary care based on a recently published
      trial (those aged 25-64, with severe chronic back pain, willing to participate in
      further research). RESULTS: The repeat prescription sample produced better
      response rates than the general sample overall (86% compared with 82%, P <
      0.001), from both genders and from the oldest and youngest age groups. The NNS
      using convenience sampling was 10 for each member of the final potential trial
      sample, compared with 55 using general population sampling. There were important
      differences between the samples in age, marital and employment status, social
      class and educational level. However, among the potential trial sample, there
      were no demographic differences. Those from the repeat prescription sample had
      poorer indices than the general population sample in all pain and health
      measures. CONCLUSIONS: The repeat prescription sampling method was approximately
      five times more efficient than the general population method. However demographic
      and clinical differences in the repeat prescription sample might hamper
      extrapolation of findings to the general population, particularly in an
      epidemiological study, and demonstrate that simple comparison with age and gender
      of the target population is insufficient.

PMID- 15722398
TI  - Developing a framework of, and quality indicators for, general practice
      management in Europe.
AB  - OBJECTIVES: To develop a framework for general practice management made up of
      quality indicators shared by six European countries. METHODS: Two-round postal
      Delphi questionnaire in the setting of general practice in Belgium, France,
      Germany, The Netherlands, Switzerland and the United Kingdom. Six national expert
      panels, each consisting of 10 members, primarily primary care practitioners and
      experts in the field of quality in primary care participated in the study. The
      main outcome measures were: (a) a European framework with indicators for the
      organization of primary care; and (b) ratings of the face validity of the
      usefulness of the indicators by expert panels in six countries. RESULTS:
      Agreement was reached about a definition of practice management across five
      domains (infrastructure, staff, information, finance, and quality and safety),
      and a common set of indicators for the organization of general practice. The
      panellist response rate was 95%. Sixty-two indicators (37%) were rated face valid
      by all six panels. Examples include out of hours service, accessibility, the
      content of doctors' bags and staff involvement in quality improvement. No
      indicators were rated invalid by all six panels. CONCLUSIONS: It proved to be
      possible to develop a European set of indicators for assessing the quality of
      practice management, despite the differences in health care systems and cultures
      in the six different countries. These indicators will now be used in a quality
      assessment procedure of practice management in nine European countries. While
      organizational indicators are part of the new GMS contract in the UK, this
      research shows that many practice management issues within primary care are also
      of relevance in other European countries.

PMID- 15722399
TI  - Antibiotic prescribing by ambulatory care physicians for adults with
      nasopharyngitis, URIs, and acute bronchitis in Taiwan: a multi-level modeling
      approach.
AB  - BACKGROUND: Imprudent prescribing of antibiotics in ambulatory care in Asia is of
      great concern. However, an adequate understanding of factors associated with
      antibiotic prescribing patterns in Asia has not been achieved. OBJECTIVE: Our aim
      was to identify patient and physician characteristics that influence antibiotic
      prescribing for adults with nasopharyngitis (common colds), upper respiratory
      tract infections (URIs) or bronchitis in Taiwan. METHODS: Generalized Estimating
      Equations (GEE) were used to analyze all 128,260 episodes of common colds, URIs
      and bronchitis generated by a random sample of 137,935 adult National Health
      Insurance (NHI) beneficiaries (> or = 18 years old) in Taiwan in 2000. RESULTS:
      Multivariate analysis results revealed substantial variations across different
      physician groups. Physician age and accreditation level of the physician's
      practice setting were the characteristics most associated with prescribing of
      antibiotics at the initial encounters for these episodes of care. Urban
      practising physicians (adjusted OR 1.69, 95% CI 1.29-2.21) and those who were
      self-dispensing or with on-site pharmacists (adjusted OR 1.32, 95% CI 1.19-1.46)
      were also higher prescribers of antibiotics for adults. Other significant
      physician predictors included physician specialty, patient volume, and ownership
      of practice setting. CONCLUSIONS: Results suggest that both accessibility to
      updated medical information and economic incentives of the attending physician
      may shape prescribing of antibiotics in ambulatory care in Taiwan. Interventions
      should be developed to influence these modifiable factors to reduce antibiotic
      prescriptions of questionable value.

PMID- 15722400
TI  - Elderly patients' and GPs' views on different methods for patient involvement: an
      international qualitative interview study.
AB  - BACKGROUND: Elderly patients' interaction with the GP may be improved through
      patient involvement techniques, and there is a variety of such techniques which
      improve patients' involvement in their own care, although little is known about
      their acceptability. OBJECTIVES: The aim of this study was to identify barriers
      and facilitators for using patient information leaflets and patient satisfaction
      questionnaires as methods for increasing elderly patients' involvement in general
      practice care by comparing their views with the GPs' views on these two types of
      methods. METHODS: In seven countries (Austria, Denmark, Germany, The Netherlands,
      Portugal, Slovenia and Switzerland) 146 GPs and 284 patients aged 70 and over
      were interviewed about the use and the acceptability of these two methods.
      Interviewers followed a semi-structured interview guide, and all interviews were
      tape-recorded and transcribed verbatim. RESULTS: The arguments for using patient
      satisfaction questionnaires were that they would provide the GP with more
      information, function as a basis for change, increase patients' self-confidence
      and make them more conscious of what to expect. Barriers for their use were
      cognitive impairment among patients, fear that they would not answer honestly and
      opposition to written material. The arguments for patient information leaflets
      were that they could support patients' memories, educate patients and promote
      their self-responsibility. The barriers were cognitive impairment among patients
      and fear that they would give them false impressions of what to expect.
      CONCLUSION: Both instruments were generally well accepted by both GPs and
      patients. Their use seemed to be dependent upon the individual GP's attitude and
      the patients' cognitive capacities.

PMID- 15722401
TI  - Efficacy of temazepam in frequent users: a series of N-of-1 trials.
AB  - BACKGROUND: Benzodiazepines are frequently prescribed for sleep disturbances.
      However, benzodiazepines are associated with side effects, and may be ineffective
      when used for a prolonged period of time. OBJECTIVES: To investigate for
      individual patients whether placebo was as effective as temazepam, or whether 10
      mg was as effective as 20 mg temazepam, and whether these results influenced
      their future temazepam use. METHODS: A series of randomized double-blind N-of-1
      trials were conducted in general practices in The Netherlands for patients who
      were using temazepam regularly. Each patient received five pairs of treatments
      consisting of one week of temazepam (10 or 20 mg) and one week of the control
      intervention (placebo or 10 mg temazepam). Per pair, the sequence of treatments
      was randomized. Main outcome measures were: time to fall asleep, and the
      individual main complaint. RESULTS: Twelve out of 15 patients completed their
      trial. In three patients there was no difference, in five a large difference, and
      in four a small difference in favour of temazepam. At follow-up, seven patients
      had stopped or reduced their temazepam use. CONCLUSION: The results regarding the
      efficacy of temazepam varied across patients. N-of-1 trials seem to be valuable
      in patients who are motivated to stop or reduce their temazepam use. They clearly
      demonstrate the efficacy of temazepam, and may give patients additional
      confidence to discontinue regular hypnotic use. The value of N-of-1 trials for
      patients who are less motivated is unclear, as the size of treatment effect does
      not seem to influence future hypnotic use.

PMID- 15722402
TI  - Cross-sensitization to morphine in cocaine-sensitized rats: behavioral
      assessments correlate with enhanced responding of ventral pallidal neurons to
      morphine and glutamate, with diminished effects of GABA.
AB  - Common neurobiological substrates contribute to the progressively increased
      behavioral effects (i.e., sensitization) that occur with repeated intermittent
      treatments of cocaine and morphine. Consequently, repeated exposure to cocaine
      can augment responding to morphine (termed cross-sensitization). Drug-induced
      sensitization in rats may model aspects of the dysfunction in motivation that are
      imposed by addiction. The ventral pallidum (VP) is involved in motivated
      behaviors and its function is altered by acute administration of cocaine and
      morphine, but the effects of repeated drug exposure remain unknown. Targeting
      this paucity, the present study evaluated electrophysiological changes in the VP
      of rats exposed to five once-daily cocaine treatments (15 mg/kg i.p.). This
      regimen also induced behavioral-sensitization that was expressed 3 days later
      when the rats received either an acute injection of cocaine (15 mg/kg i.p.) or
      morphine (10 mg/kg i.p.). VP neurons recorded in vivo 3 days after the repeated
      cocaine treatment regimen demonstrated increased excitatory responding to
      microiontophoretic applications of morphine and glutamate. The maximal effect
      (E(max)) was increased without altering potency, suggesting a change in the
      functional efficacy of the respective receptor systems. This did not represent a
      potentiation in transmission in general, for the effects of GABA were diminished.
      The results provide the first evidence for cellular adaptation in the VP after a
      sensitizing drug treatment paradigm and reveal that cross-sensitization of drug
      induced behaviors temporally correlates with changes in VP neuronal responding.
      These findings advance an emerging theme that alterations in the VP may
      contribute to the increased motivation for drug seeking that occurs in drug
      withdrawn addicts.

PMID- 15722403
TI  - Renal clearance of gamma-hydroxybutyric acid in rats: increasing renal
      elimination as a detoxification strategy.
AB  - Intoxication with gamma-hydroxybutyric acid (GHB) is associated with coma,
      seizure, and death; treatment of overdoses is symptomatic. The objectives of this
      investigation were to characterize the renal clearance and total clearance of GHB
      in rats and to evaluate potential strategies for increasing the elimination of
      GHB after drug overdoses. GHB was administered by i.v. infusion at low (108
      mg/h/kg), medium (128 mg/h/kg), or high (208 mg/h/kg) doses. Crossover studies
      were performed under steady-state conditions using the medium dose in the absence
      or presence of l-lactate, pyruvate, d-mannitol, sodium bicarbonate, or normal
      saline. GHB in plasma and urine samples was assayed using liquid chromatography
      tandem mass spectrometry. Infusion of the low, medium, and high doses of GHB
      produced steady-state plasma concentrations of 0.22 +/- 0.04, 0.43 +/- 0.05, and
      0.68 +/- 0.11 mg/ml. The renal clearance of the medium (51.8 +/- 13.0 ml/h/kg)
      and high (97.1 +/- 43.1 ml/h/kg) doses was significantly higher than that of the
      low dose (14.9 +/- 5.1 ml/h/kg), whereas the total clearance values were
      significantly lower than that of the low dose. The renal clearance was
      significantly increased by the concomitant administration of l-lactate, pyruvate,
      d-mannitol, or sodium bicarbonate with GHB but was not altered by normal saline.
      The total and metabolic clearance values were significantly increased by all
      treatments except normal saline. Overall, our results indicated that the renal
      clearance of GHB is dose-dependent, involving capacity-limited reabsorption.
      Monocarboxylate transport inhibitors, osmotic diuresis using d-mannitol, or the
      administration of sodium bicarbonate can increase the renal and total clearances
      of GHB. The approaches used in this investigation may offer potential
      detoxification strategies for the treatment of GHB overdoses.

PMID- 15722404
TI  - The acute estrogenic dilation of rat aorta is mediated solely by selective
      estrogen receptor-alpha agonists and is abolished by estrogen deprivation.
AB  - Estrogen is known to induce rapid vasodilatory response in isolated arteries.
      Because estrogen is a nonselective receptor agonist, the involvement of estrogen
      receptor (ER) subtypes in acute estrogenic responses has remained elusive. Acute
      administration of the selective ERalpha agonist 4,4',4''-(4-propyl-[(1)H]pyrazole
      1,3,5-triyl) tris-phenol (PPT) to precontracted aortic rings from intact female
      rats dose-dependently induced an ER-dependent vascular relaxation fully
      overlapping to that induced by 17beta-estradiol. By contrast, the selective
      ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) had no acute effect
      on vasomotion. This short-term vasorelaxant action of PPT was abolished by the NO
      synthase inhibitor N(omega)-nitro-l-arginine methyl ester and by endothelium
      removal. In aortic tissues from ovariectomized (OVX) rats, however, neither
      17beta-estradiol nor PPT induced acute vascular relaxation. The effect of PPT was
      restored in preparations from estrogen-replaced OVX rats, whereas DPN remained
      ineffective even after estrogen replacement. PPT acted through an ER-dependent
      mechanism, as shown by impaired response in the presence of the anti-estrogen ICI
      182,780 (7alpha,17beta-[9[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra
      1,3,5(10)-triene-3,17-diol). Accordingly, isolated rat aortic endothelial cells
      expressed both ERalpha and ERbeta. These data show that selective ERalpha but not
      ERbeta agonists reproduced the acute vasodilation of estrogen via a receptor
      mediated pathway in the aorta from intact as well as 17beta-estradiol-replaced
      OVX rats. This beneficial effect was undetectable in tissues from OVX rats.
      Selective pharmacological targeting of ER subtypes may thus represent a novel and
      promising approach in the treatment of vascular disease.

PMID- 15722405
TI  - Inhibition of human ether-a-go-go-related gene K+ channel and IKr of guinea pig
      cardiomyocytes by antipsychotic drug trifluoperazine.
AB  - Trifluoperazine, a commonly used antipsychotic drug, has been known to induce QT
      prolongation and torsades de pointes, which can cause sudden death. We studied
      the effects of trifluoperazine on the human ether-a-go-go-related gene (HERG)
      channel expressed in Xenopus oocytes and on the delayed rectifier K(+) current of
      guinea pig cardiomyocytes. The application of trifluoperazine showed a dose
      dependent decrease in current amplitudes at the end of voltage steps and tail
      currents of HERG. The IC(50) for a trifluoperazine block of HERG current
      progressively decreased according to depolarization: IC(50) values at -40, 0, and
      +40 mV were 21.6, 16.6, and 9.29 microM, respectively. The voltage dependence of
      the block could be fitted with a monoexponential function, and the fractional
      electrical distance was estimated to be delta = 0.65. The block of HERG by
      trifluoperazine was use-dependent, exhibiting more rapid onset and greater steady
      state block at higher frequencies of activation; there was partial relief of the
      block with decreasing frequency. In guinea pig ventricular myocytes, bath
      applications of 0.5 and 2 microM trifluoperazine at 36 degrees C blocked the
      rapidly activating delayed rectifier K(+) current by 32.4 and 72.9%,
      respectively; however, the same concentrations of trifluoperazine failed to
      significantly block the slowly activating delayed rectifier K(+) current. Our
      findings suggest the arrhythmogenic side effect of trifluoperazine is caused by a
      blockade of HERG and the rapid component of the delayed rectifier K(+) current
      rather than by the blockade of the slow component.

PMID- 15722406
TI  - Arsenite delays progression through each cell cycle phase and induces apoptosis
      following G2/M arrest in U937 myeloid leukemia cells.
AB  - Arsenic is a well known toxicant and carcinogen that is also effective as a
      chemotherapeutic in the treatment of acute promyelocytic leukemia. Although its
      effects on humans are well documented, arsenic's mechanism of action is not well
      understood. Its ability to act as a carcinogen and as a chemotherapeutic seems
      paradoxical. However, cancer cell transformation and cancer cell destruction can
      both occur through perturbations of the cell cycle machinery, making cell cycle
      function a likely target of arsenic action. Arsenic has previously been shown to
      inhibit cancer cell cycle progression, but the targeted cell cycle phase has been
      debated. This study was designed to identify the cell cycle phase at which U937
      cells are most sensitive to arsenite-induced growth inhibition. Centrifugal
      elutriation was used to divide asynchronous cell cultures into specific cell
      cycle phase-enriched fractions. These fractions were monitored for cell cycle
      phase progression in the presence and absence of sodium arsenite. We found an
      overall reduction in cell cycle progression rather than induction of arrest at
      one specific checkpoint. G(2)/M is the phase most sensitive to arsenite-induced
      apoptosis. However, arsenite profoundly affects U937 cell growth by increasing
      the length of time it takes cells to transit each phase of the cell cycle. Future
      study of cell cycle inhibition by arsenic should consider that the effect may not
      be mediated by the major cell cycle checkpoints. Arsenic's ability to inhibit
      growth in any cell cycle phase may increase its value as a chemotherapeutic used
      together with other, more phase-selective agents, such as camptothecin.

PMID- 15722407
TI  - alphavbeta3- and alpha5beta1-integrin blockade inhibits myogenic constriction of
      skeletal muscle resistance arterioles.
AB  - In isolated resistance arterioles with spontaneous tone, ligation of alpha4beta1-
      and alpha5beta1-integrins induces vasoconstriction whereas ligation of
      alphavbeta3-integrin induces vasodilation. However, whether integrins directly
      participate in myogenic constriction to pressure elevation is not known. To
      answer this question, isolated rat skeletal muscle arterioles were exposed to
      step increments in pressure in the absence or presence of peptides and function
      blocking antibodies known to bind alpha4beta1-, alpha5beta1-, or alphavbeta3
      integrins while vessel diameter was continually monitored. Myogenic constriction,
      as assessed by the ability of isolated arterioles to reduce their diameter in
      response to two consecutive increments in intraluminal pressure (90-110 and 110
      130 cmH2O), was not affected by treatment with any of the control peptides (RAD,
      LEV), a control antibody (anti-rat major histocompatibility complex), an
      alpha4beta1-integrin-binding peptide (LDV), or an anti-alpha4-integrin antibody.
      In contrast, alpha5beta1-integrin blockade with either anti-alpha5- or anti-beta1
      integrin antibody caused a significant inhibition of myogenic constriction. Also,
      both RGD peptide and anti-beta3-integrin antibody inhibited myogenic
      constriction. These results indicate that alpha5beta1- and alphavbeta3-integrins
      are necessary for myogenic constriction and further suggest that integrins are
      part of the mechanosensory apparatus responsible for the ability of vascular
      smooth muscle cells to detect and/or respond to changes in intraluminal pressure.

PMID- 15722408
TI  - Modulation of cardiac mast cell-mediated extracellular matrix degradation by
      estrogen.
AB  - There are fundamental differences between males and females with regard to
      susceptibility to heart disease. Although numerous animal models of heart failure
      have demonstrated that premenopausal females are afforded cardioprotection and,
      therefore, fare better in the face of cardiac disease than their male
      counterparts, many questions as to how this occurs still exist. Recently, we
      showed that 1) increased mast cell density is associated with adverse ventricular
      remodeling and 2) chemically induced mast cell degranulation using compound 48/80
      resulted in remarkable changes in matrix metalloproteinase (MMP) activity,
      cardiac collagen structure, and cardiac diastolic function in normal male rats.
      With the known gender differences in cardiac disease in mind, we sought to
      examine the effects of chemically induced cardiac mast cell degranulation in
      isolated, blood-perfused hearts of intact female rats, ovariectomized female
      rats, and ovariectomized female rats treated with 17beta-estradiol. In response
      to mast cell degranulation, no significant differences in cardiac function, MMP-2
      activity, or collagen volume fraction were observed between intact female rats
      and ovariectomized female rats treated with estrogen. In the ovariectomized
      female group, a significant rightward shift in the left ventricular pressure
      volume relation, accompanied by a marked 133% increase in active MMP-2 values
      over that in the intact female group, was noted after treatment with compound
      48/80 (P < or = 0.05), along with a significant reduction in collagen volume
      fraction below control (0.46 +/- 0.23 vs. 0.73 +/- 0.13%, P < or = 0.05). These
      findings indicate that estrogen's cardioprotective role can be partially mediated
      by its effects on cardiac mast cells, MMPs, and the extracellular matrix.

PMID- 15722409
TI  - Wave-energy patterns in carotid, brachial, and radial arteries: a noninvasive
      approach using wave-intensity analysis.
AB  - The study of wave propagation at different points in the arterial circulation may
      provide useful information regarding ventriculoarterial interactions. We describe
      a number of hemodynamic parameters in the carotid, brachial, and radial arteries
      of normal subjects by using noninvasive techniques and wave-intensity analysis
      (WIA). Twenty-one normal adult subjects (14 men and 7 women, mean age 44 +/- 6
      yr) underwent applanation tonometry and pulsed-wave Doppler studies of the right
      common carotid, brachial, and radial arteries. After ensemble averaging of the
      pressure and flow-velocity data, local hydraulic work was determined and a
      pressure-flow velocity loop was used to determine local wave speed. WIA was then
      applied to determine the magnitude, timings, and energies of individual waves. At
      all sites, forward-traveling (S) and backward-traveling (R) compression waves
      were observed in early systole. In mid- and late systole, forward-traveling
      expansion waves (X and D) were also seen. Wave speed was significantly higher in
      the brachial (6.97 +/- 0.58 m/s) and radial (6.78 +/- 0.62 m/s) arteries compared
      with the carotid artery (5.40 +/- 0.34 m/s; P < 0.05). S-wave energy was greatest
      in the brachial artery (993.5 +/- 87.8 mJ/m2), but R-wave energy was greatest in
      the radial artery (176.9 +/- 19.9 mJ/m2). X-wave energy was significantly higher
      in the brachial and radial arteries (176.4 +/- 32.7 and 163.2 +/- 30.5 mJ/m2,
      respectively) compared with the carotid artery (41.0 +/- 9.4 mJ/m2; P < 0.001).
      WIA illustrates important differences in wave patterns between peripheral
      arteries and may provide a method for understanding ventriculo-arterial
      interactions in the time domain.

PMID- 15722410
TI  - The scar neovasculature after myocardial infarction in rats.
AB  - A series of novel techniques, adapted from the field of tumor biology, were
      developed to quantify vascular structure and function and to explore the role of
      ANG II receptor AT1 in cardiac remodeling after myocardial infarction (MI). We
      examined the scar neovasculature at 1-4 wk post-MI in Sprague-Dawley rats with a
      view toward its ability to deliver and exchange oxygen. CD31 and DiOC7(3)
      staining was used to visualize anatomical vessels vs. those perfused. EF5/Cy3
      immunohistochemical staining was used to quantify tissue hypoxia. We compared
      untreated controls with rats treated with losartan, an AT1 receptor antagonist.
      Our findings indicated that, at the infarct site, there was not only a 42-75% (1
      4 wk post-MI) decrease in the number of anatomical vessels compared with controls
      but also a decrease in the fraction of perfused vessels from 70% in normal
      coronary vasculature to 48% at the infarct site. These changes were accompanied
      by progressive increases in diffusion distance and tissue hypoxia (100% increase
      in EF5/Cy3 staining at 4 wk post-MI). Losartan-treated rats exhibited a
      significantly less marked reduction in vascular perfusion and a significantly
      lesser extent of tissue hypoxia. Over the course of 4 wk post-MI, there is a
      reduction in coronary vasculature at the infarct site, the extent of which is
      attenuated by losartan. These findings implicate AT1 receptor upregulation, and
      perhaps angiotensin-related peptides, as being antiangiogenic.

PMID- 15722413
TI  - Dynamics of confined water molecules.
AB  - We present femtosecond midinfrared pump-probe measurements of the molecular
      motion and energy-transfer dynamics of a water molecule that is enclosed by
      acetone molecules. These confined water molecules show hydrogen-bond and
      orientational dynamics that are much slower than in bulk liquid water. This
      behavior is surprising because the hydrogen bonds to the C=O groups of the
      acetone molecules are weaker than the hydrogen bonds in bulk water. The energy
      transfer between the O-H groups of the confined water molecules has a time
      constant of 1.3 +/- 0.2 ps, which is >20 times slower than in bulk water. We find
      that this energy transfer is governed completely by the rate at which hydrogen
      bonds are broken and reformed, and we identify the short-lived molecular complex
      that forms the transition state of this process.

PMID- 15722411
TI  - Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of
      alpha-galactosylceramides.
AB  - A form of alpha-galactosylceramide, KRN7000, activates CD1d-restricted Valpha14
      invariant (Valpha14i) natural killer (NK) T cells and initiates multiple
      downstream immune reactions. We report that substituting the C26:0 N-acyl chain
      of KRN7000 with shorter, unsaturated fatty acids modifies the outcome of
      Valpha14i NKT cell activation. One analogue containing a diunsaturated C20 fatty
      acid (C20:2) potently induced a T helper type 2-biased cytokine response, with
      diminished IFN-gamma production and reduced Valpha14i NKT cell expansion. C20:2
      also exhibited less stringent requirements for loading onto CD1d than KRN7000,
      suggesting a mechanism for the immunomodulatory properties of this lipid. The
      differential cellular response elicited by this class of Valpha14i NKT cell
      agonists may prove to be useful in immunotherapeutic applications.

PMID- 15722412
TI  - Identification of mouse SLC39A8 as the transporter responsible for cadmium
      induced toxicity in the testis.
AB  - Testicular necrosis is a sensitive endpoint for cadmium (Cd(2+), Cd) toxicity
      across all species tested. Resistance to Cd-induced testicular damage is a
      recessive trait assigned to the Cdm locus on mouse chromosome 3. We first
      narrowed the Cdm-gene-containing region to 880 kb. SNP analysis of this region
      from two sensitive and two resistant inbred strains demonstrated a 400-kb
      haplotype block consistent with the Cd-induced toxicity phenotype; in this region
      is the Slc39a8 gene encoding a member of the solute-carrier superfamily. Slc39a8
      encodes SLC39A8 (ZIP8), whose homologs in plant and yeast are putative zinc
      transporters. We show here that ZRT-, IRT-like protein (ZIP)8 expression in
      cultured mouse fetal fibroblasts leads to a >10-fold increase in the rate of
      intracellular Cd influx and accumulation and 30-fold increase in sensitivity to
      Cd-induced cell death. The complete ZIP8 mRNA and intron-exon splice junctions
      have no nucleotide differences between two sensitive and two resistant strains of
      mice; by using situ hybridization, we found that ZIP8 mRNA is prominent in the
      vascular endothelial cells of the testis of the sensitive strains of mice but
      absent in these cells of resistant strains. Slc39a8 is therefore the Cdm gene,
      defining sensitivity to Cd toxicity specifically in vascular endothelial cells of
      the testis.

PMID- 15722414
TI  - Sterol structure determines the separation of phases and the curvature of the
      liquid-ordered phase in model membranes.
AB  - The existence of lipid rafts in biological membranes in vivo is still debated. In
      contrast, the formation of domains in model systems has been well documented. In
      giant unilamellar vesicles (GUVs) prepared from ternary mixtures of dioleoyl
      phosphatidylcholine/sphingomyelin/cholesterol, a clear separation of liquid
      disordered and sphingomyelin-enriched, liquid-ordered phases could be observed.
      This phase separation can lead to the fission of the liquid-ordered phase from
      the vesicle. Here we show that in cholesterol-containing GUVs, the phase
      separation can involve dynamic redistribution of lipids from one phase into
      another as a result of a cross-linking perturbation. We found that the molecular
      structure of a sterol used for the preparation of GUVs determines (i) its ability
      to induce phase separation and (ii) the curvature (positive or negative) of the
      formed liquid-ordered phase. As a consequence, the latter can pinch off to the
      outside or inside of the vesicle. Remarkably, some mixtures of sterols induce
      liquid-ordered domains exhibiting both positive and negative curvature, which can
      lead to a new type of budding behavior in GUVs. Our findings could have
      implications for the role of sterols in various cell-biological processes such as
      budding of secretory vesicles, endocytosis, or formation of multivesicular
      bodies.

PMID- 15722415
TI  - Mutations in Serac1 or Synj2 cause proximal t haplotype-mediated male mouse
      sterility but not transmission ratio distortion.
AB  - Transmission ratio distortion (TRD) and sterility are male-specific quantitative
      trait phenomena associated with the mouse t haplotype. TRD occurs in t haplotype
      heterozygous males and is caused by the deleterious action of distorter products
      on sperm bearing a wild-type responder locus. It has been proposed that t
      mediated male sterility is a severe manifestation of TRD caused by homozygosity
      for distorter loci; thus, the distorter and sterility loci would be identical. In
      this, study a transgenic approach was used to identify the proximal sterility
      locus, tcs1 (S1), and test its role in TRD. Mice transgenic for a wild-type
      bacterial artificial chromosome (BAC) derived from the S1-critical region were
      bred onto t haplotype backgrounds. Mating results conclusively showed that the
      BAC is sufficient to restore fertility in otherwise sterile males. Multiple
      mutations were identified in the t alleles of Synj2 and Serac1, two genes in the
      BAC; thus, they are candidates for S1. In addition, whereas the BAC transgene
      rescued sterility, it had no effect on TRD. These results uncouple the proximal t
      haplotype sterility locus, S1, from TRD, demonstrating that S1 and the proximal
      distorter locus, D1, are not the same gene.

PMID- 15722416
TI  - Chlamydia pneumoniae infection promotes a proliferative phenotype in the
      vasculature through Egr-1 activation in vitro and in vivo.
AB  - Atherosclerosis is characterized by inflammation and proliferation of vascular
      cells. The intracellular bacterium Chlamydia (Chlamydophila) pneumoniae uses
      blood monocytes [peripheral blood mononuclear cells (PBMCs)] for dissemination,
      has been found to persist in atherosclerotic lesions, and has been implicated in
      atherogenesis by small GTPase activation and T lymphocyte recruitment. Infection
      of human coronary artery smooth muscle cells with C. pneumoniae significantly
      induced mRNA and protein for the angiogenic transcription factor Egr-1, resulting
      in enhanced coronary artery smooth muscle cell proliferation, which was reduced
      by transfection with small interfering RNA duplexes targeted at Egr-1 mRNA. These
      effects required viable chlamydiae and depended on p44/42 mitogen-activated
      protein kinase activity but not on the p38 mitogen-activated protein kinase
      pathway. Postinfectious Egr-1 mRNA up-regulation in arterial vessels was
      confirmed ex vivo in a rat aortic ring model of focal vascular chlamydial
      infection. An in vivo model based on the injection of C. pneumoniae-infected
      PBMCs into mice confirmed Egr-1 mRNA up-regulation within 24 h of endovascular
      infection. Arterial injury from repeated direct chlamydial infections and cell-to
      cell contact with C. pneumoniae-infected PBMCs might represent a chronic focus of
      proliferative activity linked to the media proliferation seen in advanced
      atherosclerosis. Overall, chlamydial infection induces a proliferative phenotype
      in vascular cells via transcription factor Egr-1 activation in vitro, ex vivo,
      and in vivo.

PMID- 15722418
TI  - Collateral ventilation, the bane of bronchoscopic volume reduction.

PMID- 15722417
TI  - The initial substrate-binding site of gamma-secretase is located on presenilin
      near the active site.
AB  - gamma-Secretase is a structurally enigmatic multiprotein complex that catalyzes
      intramembrane proteolysis of a variety of substrates, including the amyloid beta
      protein precursor of Alzheimer's disease and the Notch receptor essential to cell
      differentiation. The active site of this transmembrane aspartyl protease
      apparently lies at the interface between two subunits of presenilin-1 (PS1);
      however, evidence suggests the existence of an initial substrate-binding site
      that is distinct from the active site. Here, we report that photoaffinity probes
      based on potent helical peptide inhibitors and designed to mimic the amyloid beta
      protein precursor substrate bind specifically to the PS subunit interface, at a
      site close to the active site. The location of the helical peptide-binding site
      suggests that substrate passes between the two PS1 subunits to access the active
      site. An aggressive Alzheimer-causing mutation in PS1 strongly reduced
      photolabeling by a transition-state analogue but not by helical peptides,
      providing biochemical evidence that the pathological effect of this PS mutation
      is due to alteration of the active-site topography.

PMID- 15722419
TI  - Oleic acid damages ion transport and promotes alveolar edema: the dark side of
      healthy living.

PMID- 15722420
TI  - Diagnosis and initial management of nonmalignant diseases related to asbestos.

PMID- 15722421
TI  - Diagnosis and initial management of nonmalignant diseases related to asbestos.

PMID- 15722423
TI  - Identification of plasma membrane macro- and microdomains from wavelet analysis
      of FRET microscopy.
AB  - In this study, we sought to characterize functional signaling domains by applying
      the multiresolution properties of the continuous wavelet transform to
      fluorescence resonance energy transfer (FRET) microscopic images of plasma
      membranes. A genetically encoded FRET reporter of protein kinase C (PKC)
      dependent phosphorylation was expressed in COS1 cells. Differences between
      wavelet coefficient matrices revealed several heterogeneous domains (typically
      ranging from 1 to 5 microm), reflecting the dynamic balance between PKC and
      phosphatase activity during stimulation with phorbol-12,13-dibutyrate or
      acetylcholine. The balance in these domains was not necessarily reflected in the
      overall plasma membrane changes, and observed heterogeneity was absent when cells
      were exposed to a phosphatase or PKC inhibitor. Prolonged exposure to phorbol
      12,13-dibutyrate and acetylcholine yielded more homogeneous FRET distribution in
      plasma membranes. The proposed wavelet-based image analysis provides, for the
      first time, a basis and a means of detecting and quantifying dynamic changes in
      functional signaling domains, and may find broader application in studying fine
      aspects of cellular signaling by various imaging reporters.

PMID- 15722424
TI  - Monitoring cell cycle distributions in MCF-7 cells using near-field photothermal
      microspectroscopy.
AB  - Microspectroscopic techniques such as Fourier transform infrared (FTIR) have
      played an important role in "fingerprinting" the biochemical composition of
      cellular components. Based on structure and function, complex biomolecules absorb
      energy in the mid-infrared (lambda = 2-20 microm) yielding characteristic
      vibrational infrared (IR) spectra. However, optical detection FTIR
      microspectroscopy may not be suitable for IR-absorbing sample materials.
      Photothermal microspectroscopy (PTMS) permits the direct measurement of heat
      generated as a result of sample material absorbing radiation. This approach
      generates true absorption spectra and is implemented by interfacing a scanning
      probe microscope and an FTIR spectrometer. Detection is performed using a near
      field ultra-miniaturized temperature sensor. Employing PTMS, IR spectra of MCF-7
      cells were examined in spectral regions (900-2000 cm(-1)) corresponding to
      proteins, DNA, RNA, glycoproteins, carbohydrates, lipids, and levels of protein
      phosphorylation. As a cell passes through the cell cycle, its nuclear material
      decondenses and condenses and this has led to ambiguity as to whether the
      intensity of such spectral regions may be associated with the G(1)-, S- or G(2)
      phases of the cell cycle. Cultured cells were tracked over a time course known to
      correspond to marked alterations in cell-cycle distributions, as determined using
      flow cytometry. Experiments were carried out in the absence or presence of
      lindane, a pesticide known to induce G(1)-arrest in MCF-7 cells. Significant (P <
      0.05) elevations in spectral intensities were associated with exponentially
      growing cell populations, predominantly in S-phase or G(2)-phase, compared to
      more quiescent populations predominantly in G(1)-phase. Increases in the
      absorption band at 970 cm(-1), associated with elevated protein phosphorylation,
      were observed in vibrational spectra of exponentially growing cell populations
      compared to those exhibiting a slowing in their growth kinetics. These results
      seem to suggest that intracellular bulk changes, associated with transit through
      the cell cycle, can be tracked using PTMS.

PMID- 15722425
TI  - Structure and dynamics of model pore insertion into a membrane.
AB  - A cylindrical transmembrane molecule is constructed by linking hydrophobic sites
      selected from a coarse grain model. The resulting hollow tube assembly serves as
      a representation of a transmembrane channel, pore, or a carbon nanotube. The
      interactions of a coarse grain di-myristoyl-phosphatidyl-choline hydrated bilayer
      with both a purely hydrophobic tube and a tube with hydrophilic caps are studied.
      The hydrophobic tube rotates in the membrane and becomes blocked by lipid tails
      after a few tens of nanoseconds. The hydrophilic sites of the capped tube
      stabilize it by anchoring the tube in the lipid headgroup/water interfacial
      region of each membrane leaflet. The capped tube remains free of lipid tails. The
      capped tube spontaneously conducts coarse grain water sites; the free-energy
      profile of this process is calculated using three different methods and is
      compared to the barrier for water permeation through the lipid bilayer.
      Spontaneous tube insertion into an undisturbed lipid bilayer is also studied,
      which we reported briefly in a previous publication. The hydrophobic tube
      submerges into the membrane core in a carpetlike manner. The capped tube
      laterally fuses with the closest leaflet, and then, after plunging into the
      membrane interior, rotates to assume a transbilayer orientation. Two lipids
      become trapped at the end of the tube as it penetrates the membrane. The
      hydrophilic headgroups of these lipids associate with the lower tube cap and
      assist the tube in crossing the interior of the membrane. When the rotation is
      complete these lipids detach from the tube caps and fuse with the lower leaflet
      lipids.

PMID- 15722426
TI  - Interpreting biomagnetic fields of planar wave fronts in cardiac muscle.
AB  - The recent results of Holzer and co-workers reveal the existence of net currents
      that flow along the front of a planar wave propagating through cardiac tissue.
      This is an important contribution toward the better understanding of the physics
      of biomagnetic fields. However, although the authors claim their results reveal
      particular bidomain properties, we show in this short letter that the results
      allow multiple interpretations. For instance, cardiac anisotropy by itself may
      also explain the existence of a net current along the wave front. Based on our
      calculations, we suggest additional experiments that would allow distinguishing
      between these two explanations and thus provide further evidence on the basic
      physics behind cardiac biomagnetism.

PMID- 15722427
TI  - Normal-modes-based prediction of protein conformational changes guided by
      distance constraints.
AB  - Based on the elastic network model, we develop a novel method that predicts the
      conformational change of a protein complex given its initial-state crystal
      structure together with a small set of pairwise distance constraints for the end
      state. The predicted conformational change, which is a linear combination of
      multiple low-frequency normal modes that are solved from the elastic network
      model, is computed as a response displacement induced by a perturbation to the
      system Hamiltonian that incorporates the given distance constraints. For a list
      of test cases, we find that the computed response displacement overlaps
      significantly with the measured conformational changes, when only a handful of
      pairwise constraints are used (</=10). The performance of this method is also
      shown to be robust against different choices of pairwise distance constraints and
      errors in their values. This method, if supplied with the experimentally derived
      distance constraints (for example, from NMR or other spectroscopic measurements),
      can be applied to the analysis of protein conformational changes toward transient
      states.

PMID- 15722429
TI  - Mechanism of membrane activity of the antibiotic trichogin GA IV: a two-state
      transition controlled by peptide concentration.
AB  - Synthetic fluorescent analogs of the natural lipopeptide trichogin GA IV were
      used to investigate the peptide position and orientation in model membranes. A
      translocation assay based on Forster energy transfer indicates that trichogin is
      associated to both the outer and inner leaflet of the membrane, even at low
      concentration, when it is not active. Fluorescence quenching measurements,
      performed by using water soluble quenchers and quenchers positioned in the
      membrane at different depths, indicate that at low membrane-bound peptide/lipid
      ratios trichogin lies close to the region of polar headgroups. By increasing
      peptide concentration until membrane leakage takes place, a cooperative
      transition occurs and a significant fraction of the peptide becomes deeply buried
      into the bilayer. Remarkably, this change in peptide position is strictly coupled
      with peptide aggregation. Therefore, the mechanism of trichogin action can be
      envisaged as based on a two-state transition controlled by peptide concentration.
      One state is the monomeric, surface bound and inactive peptide, and the other
      state is a buried, aggregated form, which is responsible for membrane leakage and
      bioactivity.

PMID- 15722430
TI  - Molecular dynamics simulation of the M2 helices within the nicotinic
      acetylcholine receptor transmembrane domain: structure and collective motions.
AB  - Multiple nanosecond duration molecular dynamics simulations were performed on the
      transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded
      within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were
      free to move, whereas the outer (M1, M3, M4) helix bundle was backbone
      restrained. The M2 helices largely retain their hydrogen-bonding pattern
      throughout the simulation, with some distortions in the helical end and loop
      regions. All of the M2 helices exhibit bending motions, with the hinge point in
      the vicinity of the central hydrophobic gate region (corresponding to residues
      alphaL251 and alphaV255). The bending motions of the M2 helices lead to a degree
      of dynamic narrowing of the pore in the region of the proposed hydrophobic gate.
      Calculations of Born energy profiles for various structures along the simulation
      trajectory suggest that the conformations of the M2 bundle sampled correspond to
      a closed conformation of the channel. Principal components analyses of each of
      the M2 helices, and of the five-helix M2 bundle, reveal concerted motions that
      may be relevant to channel function. Normal mode analyses using the anisotropic
      network model reveal collective motions similar to those identified by principal
      components analyses.

PMID- 15722431
TI  - Structure of cholesterol/ceramide monolayer mixtures: implications to the
      molecular organization of lipid rafts.
AB  - The structure of monolayers of cholesterol/ceramide mixtures was investigated
      using grazing incidence x-ray diffraction, immunofluorescence, and atomic force
      microscopy techniques. Grazing incidence x-ray diffraction measurements showed
      the existence of a crystalline mixed phase of the two components within a range
      of compositions of cholesterol/ceramide between 100:0 and 67:33. The mixed phase
      coexists with the ceramide crystalline phase in the range of compositions between
      50:50 and 30:70; between 30:70 and 0:100 only the highly crystalline phase of
      ceramide was detected. The latter was determined and modeled. Immunolabeling was
      performed with an antibody specific to the cholesterol monohydrate crystalline
      arrangement. The antibody recognizes crystalline cholesterol monolayers, but does
      not interact with crystalline ceramide. Immunofluorescence and atomic force
      microscopy data show that in uncompressed ceramide monolayers, the highly
      crystalline phase coexists with a disordered loosely packed phase. In contrast,
      no disordered phase coexists with the new crystalline mixed phase. We conclude
      that the new mixed phase represents a stable homogeneous arrangement of
      cholesterol with ceramide. As ceramide incorporates the lipid backbone common to
      all sphingolipids, this arrangement may be relevant to the understanding of the
      molecular organization of lipid rafts.

PMID- 15722433
TI  - Optical deformability as an inherent cell marker for testing malignant
      transformation and metastatic competence.
AB  - The relationship between the mechanical properties of cells and their molecular
      architecture has been the focus of extensive research for decades. The
      cytoskeleton, an internal polymer network, in particular determines a cell's
      mechanical strength and morphology. This cytoskeleton evolves during the normal
      differentiation of cells, is involved in many cellular functions, and is
      characteristically altered in many diseases, including cancer. Here we examine
      this hypothesized link between function and elasticity, enabling the distinction
      between different cells, by using a microfluidic optical stretcher, a two-beam
      laser trap optimized to serially deform single suspended cells by optically
      induced surface forces. In contrast to previous cell elasticity measurement
      techniques, statistically relevant numbers of single cells can be measured in
      rapid succession through microfluidic delivery, without any modification or
      contact. We find that optical deformability is sensitive enough to monitor the
      subtle changes during the progression of mouse fibroblasts and human breast
      epithelial cells from normal to cancerous and even metastatic state. The
      surprisingly low numbers of cells required for this distinction reflect the tight
      regulation of the cytoskeleton by the cell. This suggests using optical
      deformability as an inherent cell marker for basic cell biological investigation
      and diagnosis of disease.

PMID- 15722432
TI  - A molecular-mechanical model of the microtubule.
AB  - Dynamic instability of MTs is thought to be regulated by biochemical
      transformations within tubulin dimers that are coupled to the hydrolysis of bound
      GTP. Structural studies of nucleotide-bound tubulin dimers have recently provided
      a concrete basis for understanding how these transformations may contribute to MT
      dynamic instability. To analyze these ideas, we have developed a molecular
      mechanical model in which structural and biochemical properties of tubulin are
      used to predict the shape and stability of MTs. From simple and explicit features
      of tubulin, we define bond energy relationships and explore the impact of their
      variations on integral MT properties. This modeling provides quantitative
      predictions about the GTP cap. It specifies important mechanical features
      underlying MT instability and shows that this property does not require GTP
      hydrolysis to alter the strength of tubulin-tubulin bonds. The MT plus end is
      stabilized by at least two layers of GTP-tubulin subunits, whereas the minus end
      requires at least one; this and other differences between the ends are explained
      by asymmetric force balances. Overall, this model provides a new link between the
      biophysical characteristics of tubulin and the physiological behavior of MTs. It
      will also be useful in building a more complete description of MT dynamics and
      mechanics.

PMID- 15722434
TI  - Comments on the article "The universal dynamics of tumor growth" by A. Bru et al.

PMID- 15722435
TI  - Influence of DPH on the structure and dynamics of a DPPC bilayer.
AB  - We have conducted extensive molecular dynamics (MD) simulations together with
      differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR)
      experiments to quantify the influence of free 1,6-diphenyl-1,3,5-hexatriene (DPH)
      fluorescent probes on the structure and dynamics of a
      dipalmitoylphosphatidylcholine bilayer. Atomistic MD simulations show that in the
      membrane-water interface the influence of DPH is minor, whereas in the acyl-chain
      region DPH gives rise to major perturbations. In the latter case, DPH is found to
      influence a wide range of membrane properties, such as the packing and ordering
      of hydrocarbon tails and the lateral diffusion of lipid molecules. The effects
      are prominent but of local nature, i.e., the changes observed in the properties
      of lipid molecules are significant in the vicinity of DPH, but reduce rapidly as
      the distance from the probe increases. Long-range perturbations due to DPH are
      hence not expected. Detailed DSC and (2)H NMR measurements support this view. DSC
      shows only subtle perturbation to the cooperative behavior of the membrane system
      in the presence of DPH, and (2)H NMR shows that DPH gives rise to a slight
      increase in the lipid chain order, in agreement with MD simulations. Potential
      effects of other probes such as pyrene are briefly discussed.

PMID- 15722436
TI  - EPR studies of chlorocatechol 1,2-dioxygenase: evidences of iron reduction during
      catalysis and of the binding of amphipatic molecules.
AB  - Chlorocatechol 1,2-dioxygenase from Pseudomonas putida (Pp 1,2-CCD) is a
      dioxygenase responsible for ring cleavage during the degradation of recalcitrant
      aromatic compounds. We determined the zero-field splitting of the Fe(III)
      cofactor (|D| = 1.3 +/- 0.2 cm(-1)) by electron paramagnetic resonance (EPR)
      experiments that along with other structural data allowed us to infer the Fe(III)
      coordination environment. The EPR spectrum of the ion shows a significantly
      decrease of the g = 4.3 resonance upon substrate binding. This result is
      rationalized in terms of a mechanism previously proposed, where catechol
      substrate is activated by Fe(III), yielding an exchange-coupled Fe(II)
      semiquinone (pair). The Pp 1,2-CCD capacity of binding amphipatic molecules and
      the effects of such binding on protein activity are also investigated. EPR
      spectra of spin labels show a protein-bound component, which was characterized by
      means of spectral simulations. Our results indicate that Pp 1,2-CCD is able to
      bind amphipatic molecules in a channel with the headgroup pointing outwards into
      the solvent, whereas the carbon chain is held inside the tunnel. Protein assays
      show that the enzyme activity is significantly lowered in the presence of stearic
      acid molecules. The role of the binding of those molecules as an enzyme activity
      modulator is discussed.

PMID- 15722437
TI  - Predicting the signaling state of photoactive yellow protein.
AB  - As a bacterial blue light sensor the photoactive yellow protein (PYP) undergoes
      conformational changes upon signal transduction. The absorption of a photon
      triggers a series of events that are initially localized around the protein
      chromophore, extends to encompass the whole protein within microseconds, and
      leads to the formation of the transient pB signaling state. We study the
      formation of this signaling state pB by molecular simulation and predict its
      solution structure. Conventional straightforward molecular dynamics is not able
      to address this formation process due to the long (microsecond) timescales
      involved, which are (partially) caused by the presence of free energy barriers
      between the metastable states. To overcome these barriers, we employed the
      parallel tempering (or replica exchange) method, thus enabling us to predict
      qualitatively the formation of the PYP signaling state pB. In contrast to the
      receptor state pG of PYP, the characteristics of this predicted pB structure
      include a wide open chromophore-binding pocket, with the chromophore and Glu(46)
      fully solvent-exposed. In addition, loss of alpha-helical structure occurs,
      caused by the opening motion of the chromophore-binding pocket and the disruptive
      interaction of the negatively charged Glu(46) with the backbone atoms in the
      hydrophobic core of the N-terminal cap. Recent NMR experiments agree very well
      with these predictions.

PMID- 15722438
TI  - Hinge-like motions in RNA kink-turns: the role of the second a-minor motif and
      nominally unpaired bases.
AB  - Kink-turn (K-turn) motifs are asymmetric internal loops found at conserved
      positions in diverse RNAs, with sharp bends in phosphodiester backbones producing
      V-shaped structures. Explicit-solvent molecular dynamics simulations were carried
      out for three K-turns from 23S rRNA, i.e., Kt-38 located at the base of the A
      site finger, Kt-42 located at the base of the L7/L12 stalk, and Kt-58 located in
      domain III, and for the K-turn of human U4 snRNA. The simulations reveal hinge
      like K-turn motions on the nanosecond timescale. The first conserved A-minor
      interaction between the K-turn stems is entirely stable in all simulations. The
      angle between the helical arms of Kt-38 and Kt-42 is regulated by local
      variations of the second A-minor (type I) interaction between the stems. Its
      variability ranges from closed geometries to open ones stabilized by insertion of
      long-residency waters between adenine and cytosine. The simulated A-minor
      geometries fully agree with x-ray data. Kt-58 and Kt-U4 exhibit similar elbow
      like motions caused by conformational change of the adenosine from the nominally
      unpaired region. Despite the observed substantial dynamics of K-turns, key
      tertiary interactions are stable and no sign of unfolding is seen. We suggest
      that some K-turns are flexible elements mediating large-scale ribosomal motions
      during the protein synthesis cycle.

PMID- 15722440
TI  - Identification and localization of prostaglandin E2 receptors in upper and lower
      segment human myometrium during pregnancy.
AB  - Prostaglandin E2 (PGE2) plays a key role in the maintenance of human pregnancy
      and labour onset. PGE2 can elicit diverse actions within the uterus depending on
      the PGE2 receptors (EP1, EP2, EP3 and EP4) expressed. By signalling through
      different intracellular pathways the EP receptors may inhibit or promote smooth
      muscle contractility. Nine different EP3 receptor splice variants have been
      identified with divergent signalling pathways. RT-PCR and immunohistochemistry
      were utilized to identify and localize EP receptor isoforms within the upper
      segment (US) and lower segment (LS) myometrium. EP1 was significantly increased
      in the LS myometrium with term labour. EP3 (and EP3 splice variants EP3I(1b),
      EP3II, EP3III and EP3IV) was down-regulated in pregnancy (US and/or LS) with a
      further decrease at term labour in the LS. Overall, expression of EP2 was
      significantly higher in the LS while EP3 was significantly higher in the US. No
      significant EP4 changes were observed. Consistent with the RT-PCR results,
      immunohistochemistry confirmed the presence and, interestingly, showed nuclear
      localization of EP receptors in the myometrium with higher EP1 expression and
      lower expression of EP3. The differential regulation of EP receptors within the
      myometrium indicates that they may play a role in controlling the onset and
      maintenance of human labour.

PMID- 15722439
TI  - Spatiotemporal image correlation spectroscopy (STICS) theory, verification, and
      application to protein velocity mapping in living CHO cells.
AB  - We introduce a new extension of image correlation spectroscopy (ICS) and image
      cross-correlation spectroscopy (ICCS) that relies on complete analysis of both
      the temporal and spatial correlation lags for intensity fluctuations from a laser
      scanning microscopy image series. This new approach allows measurement of both
      diffusion coefficients and velocity vectors (magnitude and direction) for
      fluorescently labeled membrane proteins in living cells through monitoring of the
      time evolution of the full space-time correlation function. By using filtering in
      Fourier space to remove frequencies associated with immobile components, we are
      able to measure the protein transport even in the presence of a large fraction
      (>90%) of immobile species. We present the background theory, computer
      simulations, and analysis of measurements on fluorescent microspheres to
      demonstrate proof of principle, capabilities, and limitations of the method. We
      demonstrate mapping of flow vectors for mixed samples containing fluorescent
      microspheres with different emission wavelengths using space time image cross
      correlation. We also present results from two-photon laser-scanning microscopy
      studies of alpha-actinin/enhanced green fluorescent protein fusion constructs at
      the basal membrane of living CHO cells. Using space-time image correlation
      spectroscopy (STICS), we are able to measure protein fluxes with magnitudes of
      mum/min from retracting lamellar regions and protrusions for adherent cells. We
      also demonstrate the measurement of correlated directed flows (magnitudes of
      mum/min) and diffusion of interacting alpha5 integrin/enhanced cyan fluorescent
      protein and alpha-actinin/enhanced yellow fluorescent protein within living CHO
      cells. The STICS method permits us to generate complete transport maps of
      proteins within subregions of the basal membrane even if the protein
      concentration is too high to perform single particle tracking measurements.

PMID- 15722441
TI  - Ligand activated relaxin receptor increases the transcription of IGFBP-1 and
      prolactin in human decidual and endometrial stromal cells.
AB  - The aim of this study was to investigate relaxin (RLX) receptor-mediated gene
      activation in human endometrium. We determined the promoter activities of insulin
      like growth factor binding protein-1 (IGFBP-1) and prolactin (PRL) and identified
      sequence(s) that mediate RLX activated transcription in human decidual cells and
      endometrial stromal cells. In human decidual cells, the promoter activity of
      IGFBP-1 was increased significantly in cells incubated with RLX. In endometrial
      stromal cells, the RLX mediated activation was enhanced only when stromal cells
      were co-transfected with RLX-receptor (LGR7) expression vector and RLX alone had
      little effect (Mazella et al., 2004). Deletion and mutation analysis showed that
      the cAMP regulatory element (CRE, -263 to -259 bp) in the IGFBP-1 promoter was
      essential for the activation. In addition, RLX increased the phosphorylation of
      CRE binding protein (CREB to p-CREB) and p-CREB resided in the nucleus,
      indicating that RLX activates the protein kinase (PKA) system in decidual cells.
      Gel shift assay showed that nuclear extracts prepared from RLX treated decidual
      cells increased the binding to the CRE site of the IGFBP-1 promoter. RLX
      increased the PRL promoter activity mediated through the region containing
      multiple CCAAT/enhancer-binding proteins (C/EBP) binding sites that have been
      shown to mediate the PRL gene activation by cAMP analogue (Pohnke et al., 1999).
      RLX enhanced IGFBP-1 promoter activity was inhibited by cAMP dependent PKA
      inhibitor, H-89. PRL promoter activity was inhibited by both H-89 and U0126
      indicating multiple signalling pathways are activated by RLX in endometrial cells
      for different target gene activation.

PMID- 15722442
TI  - Contributions of hydrophobic domain interface interactions to the folding and
      stability of human gammaD-crystallin.
AB  - Human gammaD-crystallin (HgammaD-Crys) is a monomeric eye lens protein composed
      of two highly homologous beta-sheet domains. The domains interact through
      interdomain side chain contacts forming two structurally distinct regions, a
      central hydrophobic cluster and peripheral residues. The hydrophobic cluster
      contains Met43, Phe56, and Ile81 from the N-terminal domain (N-td) and Val132,
      Leu145, and Val170 from the C-terminal domain (C-td). Equilibrium
      unfolding/refolding of wild-type HgammaD-Crys in guanidine hydrochloride (GuHCl)
      was best fit to a three-state model with transition midpoints of 2.2 and 2.8 M
      GuHCl. The two transitions likely corresponded to sequential unfolding/refolding
      of the N-td and the C-td. Previous kinetic experiments revealed that the C-td
      refolds more rapidly than the N-td. We constructed alanine substitutions of the
      hydrophobic interface residues to analyze their roles in folding and stability.
      After purification from E. coli, all mutant proteins adopted a native-like
      structure similar to wild type. The mutants F56A, I81A, V132A, and L145A had a
      destabilized N-td, causing greater population of the single folded domain
      intermediate. Compared to wild type, these mutants also had reduced rates for
      productive refolding of the N-td but not the C-td. These data suggest a refolding
      pathway where the domain interface residues of the refolded C-td act as a
      nucleating center for refolding of the N-td. Specificity of domain interface
      interactions is likely important for preventing incorrect associations in the
      high protein concentrations of the lens nucleus.

PMID- 15722443
TI  - Hsp20, a novel alpha-crystallin, prevents Abeta fibril formation and toxicity.
AB  - Beta-amyloid (Abeta) is a major protein component of senile plaques in
      Alzheimer's disease, and is neurotoxic when aggregated. The size of aggregated
      Abeta responsible for the observed neurotoxicity and the mechanism of aggregation
      are still under investigation; however, prevention of Abeta aggregation still
      holds promise as a means to reduce Abeta neurotoxicity. In research presented
      here, we show that Hsp20, a novel alpha-crystallin isolated from the bovine
      erythrocyte parasite Babesia bovis, was able to prevent aggregation of denatured
      alcohol dehydrogenase when the two proteins are present at near equimolar levels.
      We then examined the ability of Hsp20 produced as two different fusion proteins
      to prevent Abeta amyloid formation as indicated by Congo Red binding; we found
      that not only was Hsp20 able to dramatically reduce Congo Red binding, but it was
      able to do so at molar ratios of Hsp20 to Abeta of 1 to 1000. Electron microscopy
      confirmed that Hsp20 does prevent Abeta fibril formation. Hsp20 was also able to
      significantly reduce Abeta toxicity to both SH-SY5Y and PC12 neuronal cells at
      similar molar ratios. At high concentrations of Hsp20, the protein no longer
      displays its aggregation inhibition and toxicity attenuation properties. Size
      exclusion chromatography indicated that Hsp20 was active at low concentrations in
      which dimer was present. Loss of activity at high concentrations was associated
      with the presence of higher oligomers of Hsp20. This work could contribute to the
      development of a novel aggregation inhibitor for prevention of Abeta toxicity.

PMID- 15722444
TI  - Normal modes for predicting protein motions: a comprehensive database assessment
      and associated Web tool.
AB  - We carry out an extensive statistical study of the applicability of normal modes
      to the prediction of mobile regions in proteins. In particular, we assess the
      degree to which the observed motions found in a comprehensive data set of 377
      nonredundant motions can be modeled by a single normal-mode vibration. We
      describe each motion in our data set by vectors connecting corresponding atoms in
      two crystallographically known conformations. We then measure the geometric
      overlap of these motion vectors with the displacement vectors of the lowest
      frequency mode, for one of the conformations. Our study suggests that the lowest
      mode contains useful information about the parts of a protein that move most
      (i.e., have the largest amplitudes) and about the direction of this movement.
      Based on our findings, we developed a Web tool for motion prediction (available
      from http://molmovdb.org/nma) and apply it here to four representative motions-
      from bacteriorhodopsin, calmodulin, insulin, and T7 RNA polymerase.

PMID- 15722445
TI  - Insights into the domains required for dimerization and assembly of human alphaB
      crystallin.
AB  - Protein pin array technology was used to identify subunit-subunit interaction
      sites in the small heat shock protein (sHSP) alphaB crystallin. Subunit-subunit
      interaction sites were defined as consensus sequences that interacted with both
      human alphaA crystallin and alphaB crystallin. The human alphaB crystallin
      protein pin array consisted of contiguous and overlapping peptides, eight amino
      acids in length, immobilized on pins that were in a 96-well ELISA plate format.
      The interaction of alphaB crystallin peptides with physiological partner
      proteins, alphaA crystallin and alphaB crystallin, was detected using antibodies
      and recorded using spectrophotometric absorbance. Five peptide sequences
      including 37LFPTSTSLSPFYLRPPSF54 in the N terminus, 75FSVNLDVK82)(beta3),
      131LTITSSLS138 (beta8) and 141GVLTVNGP148 (beta9) that form beta strands in the
      conserved alpha crystallin core domain, and 155PERTIPITREEK166 in the C-terminal
      extension were identified as subunit-subunit interaction sites in human alphaB
      crystallin using the novel protein pin array assay. The subunit-subunit
      interaction sites were mapped to a three-dimensional (3D) homology model of wild
      type human alphaB crystallin that was based on the crystal structure of wheat
      sHSP16.9 and Methanococcus jannaschi sHSP16.5 (Mj sHSP16.5). The subunit-subunit
      interaction sites identified and mapped onto the homology model were solvent
      exposed and had variable secondary structures ranging from beta strands to random
      coils and short alpha helices. The subunit-subunit interaction sites formed a
      pattern of hydrophobic patches on the 3D surface of human alphaB crystallin.

PMID- 15722446
TI  - Test of the Binding Threshold Hypothesis for olfactory receptors: explanation of
      the differential binding of ketones to the mouse and human orthologs of olfactory
      receptor 912-93.
AB  - We tested the Binding Threshold Hypothesis (BTH) for activation of olfactory
      receptors (ORs): To activate an OR, the odorant must bind to the OR with binding
      energy above some threshold value. The olfactory receptor (OR) 912-93 is known
      experimentally to be activated by ketones in mouse, but is inactive to ketones in
      human, despite an amino acid sequence identity of approximately 66%. To
      investigate the origins of this difference, we used the MembStruk first
      principles method to predict the tertiary structure of the mouse OR 912-93
      (mOR912-93), and the HierDock first-principles method to predict the binding site
      for ketones to this receptor. We found that the strong binding of ketones to
      mOR912-93 is dominated by a hydrogen bond of the ketone carbonyl group to Ser105.
      All ketones predicted to have a binding energy stronger than EBindThresh = 26
      kcal/mol were observed experimentally to activate this OR, while the two ketones
      predicted to bind more weakly do not. In addition, we predict that 2-undecanone
      and 2-dodecanone both bind sufficiently strongly to activate mOR912-93. A similar
      binding site for ketones was predicted in hOR912-93, but the binding is much
      weaker because the human ortholog has a Gly at the position of Ser105. We predict
      that mutating this Gly to Ser in human should lead to activation of hOR912-93 by
      these ketones. Experimental substantiations of the above predictions would
      provide further tests of the validity of the BTH, our predicted 3D structures,
      and our predicted binding sites for these ORs.

PMID- 15722447
TI  - Structure and mechanism of ADP-ribose-1''-monophosphatase (Appr-1''-pase), a
      ubiquitous cellular processing enzyme.
AB  - Appr-1''-pase, an important and ubiquitous cellular processing enzyme involved in
      the tRNA splicing pathway, catalyzes the conversion of ADP-ribose
      1''monophosphate (Appr-1''-p) to ADP-ribose. The structures of the native enzyme
      from the yeast and its complex with ADP-ribose were determined to 1.9 A and 2.05
      A, respectively. Analysis of the three-dimensional structure of this protein,
      selected as a target in a structural genomics project, reveals its putative
      function and provides clues to the catalytic mechanism. The structure of the 284
      amino acid protein shows a two-domain architecture consisting of a three-layer
      alphabetaalpha sandwich N-terminal domain connected to a small C-terminal helical
      domain. The structure of Appr-1''-pase in complex with the product, ADP-ribose,
      reveals an active-site water molecule poised for nucleophilic attack on the
      terminal phosphate group. Loop-region residues Asn 80, Asp 90, and His 145 may
      form a catalytic triad.

PMID- 15722448
TI  - Microsecond timescale backbone conformational dynamics in ubiquitin studied with
      NMR R1rho relaxation experiments.
AB  - NMR spin relaxation experiments are used to characterize the dynamics of the
      backbone of ubiquitin. Chemical exchange processes affecting residues Ile 23, Asn
      25, Thr 55, and Val 70 are characterized using on- and off-resonance rotating
      frame 15N R1rho relaxation experiments to have a kinetic exchange rate constant
      of 25,000 sec(-1) at 280 K. The exchange process affecting residues 23, 25, and
      55 appears to result from disruption of N-cap hydrogen bonds of the alpha-helix
      and possibly from repacking of the side chain of Ile 23. Chemical exchange
      processes affecting other residues on the surface of ubiquitin are identified
      using 1H-15N multiple quantum relaxation experiments. These residues are located
      near or at the regions known to interact with various enzymes of the ubiquitin
      dependent protein degradation pathway.

PMID- 15722449
TI  - Structural and mechanistic studies of chloride induced activation of human
      pancreatic alpha-amylase.
AB  - The mechanism of allosteric activation of alpha-amylase by chloride has been
      studied through structural and kinetic experiments focusing on the chloride
      dependent N298S variant of human pancreatic alpha-amylase (HPA) and a chloride
      independent TAKA-amylase. Kinetic analysis of the HPA variant clearly
      demonstrates the pronounced activating effect of chloride ion binding on reaction
      rates and its effect on the pH-dependence of catalysis. Structural alterations
      observed in the N298S variant upon chloride ion binding suggest that the chloride
      ion plays a variety of roles that serve to promote catalysis. One of these is
      having a strong influence on the positioning of the acid/base catalyst residue
      E233. Absence of chloride ion results in multiple conformations for this residue
      and unexpected enzymatic products. Chloride ion and N298 also appear to stabilize
      a helical region of polypeptide chain from which projects the flexible substrate
      binding loop unique to chloride-dependent alpha-amylases. This structural feature
      also serves to properly orient the catalytically essential residue D300.
      Comparative analyses show that the chloride-independent alpha-amylases compensate
      for the absence of bound chloride by substituting a hydrophobic core, altering
      the manner in which substrate interactions are made and shifting the placement of
      N298. These evolutionary differences presumably arise in response to alternative
      operating environments or the advantage gained in a particular product profile.
      Attempts to engineer chloride-dependence into the chloride-independent TAKA
      amylase point out the complexity of this system, and the fact that a multitude of
      factors play a role in binding chloride ion in the chloride-dependent alpha
      amylases.

PMID- 15722450
TI  - Impact of remote mutations on metallo-beta-lactamase substrate specificity:
      implications for the evolution of antibiotic resistance.
AB  - Metallo-beta-lactamases have raised concerns due to their ability to hydrolyze a
      broad spectrum of beta-lactam antibiotics. The G262S point mutation
      distinguishing the metallo-beta-lactamase IMP-1 from IMP-6 has no effect on the
      hydrolysis of the drugs cephalothin and cefotaxime, but significantly improves
      catalytic efficiency toward cephaloridine, ceftazidime, benzylpenicillin,
      ampicillin, and imipenem. This change in specificity occurs even though residue
      262 is remote from the active site. We investigated the substrate specificities
      of five other point mutants resulting from single-nucleotide substitutions at
      positions near residue 262: G262A, G262V, S121G, F218Y, and F218I. The results
      suggest two types of substrates: type I (nitrocefin, cephalothin, and
      cefotaxime), which are converted equally well by IMP-6, IMP-1, and G262A, but
      even more efficiently by the other mutants, and type II (ceftazidime,
      benzylpenicillin, ampicillin, and imipenem), which are hydrolyzed much less
      efficiently by all the mutants. G262V, S121G, F218Y, and F218I improve conversion
      of type I substrates, whereas G262A and IMP-1 improve conversion of type II
      substrates, indicating two distinct evolutionary adaptations from IMP-6.
      Substrate structure may explain the catalytic efficiencies observed. Type I
      substrates have R2 electron donors, which may stabilize the substrate
      intermediate in the binding pocket. In contrast, the absence of these stabilizing
      interactions with type II substrates may result in poor conversion. This
      observation may assist future drug design. As the G262A and F218Y mutants confer
      effective resistance to Escherichia coli BL21(DE3) cells (high minimal inhibitory
      concentrations), they are likely to evolve naturally.

PMID- 15722451
TI  - Binding of the anti-tubercular drug isoniazid to the arylamine N
      acetyltransferase protein from Mycobacterium smegmatis.
AB  - Isoniazid is a frontline drug used in the treatment of tuberculosis (TB).
      Isoniazid is a prodrug, requiring activation in the mycobacterial cell by the
      catalase/peroxidase activity of the katG gene product. TB kills two million
      people every year and the situation is getting worse due to the increase in
      prevalence of HIV/AIDS and emergence of multidrug-resistant strains of TB.
      Arylamine N-acetyltransferase (NAT) is a drug-metabolizing enzyme (E.C. 2.1.3.5).
      NAT can acetylate isoniazid, transferring an acetyl group from acetyl coenzyme A
      onto the terminal nitrogen of the drug, which in its N-acetylated form is
      therapeutically inactive. The bacterium responsible for TB, Mycobacterium
      tuberculosis, contains and expresses the gene encoding the NAT protein. Isoniazid
      binds to the NAT protein from Salmonella typhimurium and we report here the mode
      of binding of isoniazid in the NAT enzyme from Mycobacterium smegmatis, closely
      related to the M. tuberculosis and S. typhimurium NAT enzymes. The mode of
      binding of isoniazid to M. smegmatis NAT has been determined using data collected
      from two distinct crystal forms. We can say with confidence that the observed
      mode of binding of isoniazid is not an artifact of the crystallization conditions
      used. The NAT enzyme is active in mycobacterial cells and we propose that
      isoniazid binds to the NAT enzyme in these cells. NAT activity in M. tuberculosis
      is likely therefore to modulate the degree of activation of isoniazid by other
      enzymes within the mycobacterial cell. The structure of NAT with isoniazid bound
      will facilitate rational drug design for anti-tubercular therapy.

PMID- 15722453
TI  - Ligand-binding regulation of LXR/RXR and LXR/PPAR heterodimerizations: SPR
      technology-based kinetic analysis correlated with molecular dynamics simulation.
AB  - Liver X receptor (LXR) and peroxisome proliferator-activated receptor (PPAR) are
      two members of nuclear receptors involved in the nutrient metabolisms of dietary
      fatty acid and cholesterol. They are found to be of cross-talk function in that
      LXR regulates fatty acid synthesis and PPAR controls fatty acid degradation. LXRs
      (LXRalpha and LXRbeta) function by forming obligate heterodimers with the
      retinoid X receptor (RXR), and subsequently binding to specific DNA response
      elements within the regulatory regions of their target genes. In this work, the
      kinetic features concerning LXR/RXR and LXR/PPAR interactions have been fully
      investigated using surface plasmon resonance (SPR) technology. It is found that
      LXRs could bind to all the three PPAR subtypes, PPARalpha, PPARgamma and
      PPARdelta with different binding affinities, and such receptor/receptor
      interactions could be regulated by ligand binding. Moreover, molecular dynamics
      (MD) simulations were performed on six typical complex models. The results
      revealed that ligands may increase the interaction energies between the receptor
      interfaces of the simulated receptor/receptor complexes. The MD results are in
      agreement with the SPR data. Further analyses on the MD results indicated that
      the ligand binding might increase the hydrogen bonds between the interfaces of
      the receptor/receptor complex.

PMID- 15722452
TI  - Dynamics of the gp130 cytokine complex: a model for assembly on the cellular
      membrane.
AB  - Cytokines of the interleukin-6 (IL-6)-type family all bind to the glycoprotein
      gp130 on the cell surface and require interaction with two gp130 or one gp130 and
      another related signal transducing receptor subunit. In addition, some cytokines
      of this family, such as IL-6, interleukin-11, ciliary neurotrophic factor,
      neuropoietin, cardiotrophin-1, and cardiotrophin-1-like-cytokine, interact with
      specific ligand binding receptor proteins. High- and low-affinity binding sites
      have been determined for these cytokines. So far, however, the stoichiometry of
      the signaling receptor complexes has remained unclear, because the formation of
      the cytokine/cytokine-receptor complexes has been analyzed with soluble receptor
      components in solution, which do not necessarily reflect the situation on the
      cellular membrane. Consequently, the binding affinities measured in solution have
      been orders of magnitude below the values obtained with whole cells. We have
      expressed two gp130 extracellular domains in the context of a Fc-fusion protein,
      which fixes the receptors within one dimension and thereby restricts the
      flexibility of the proteins in a fashion similar to that within the plasma
      membrane. We measured binding of IL-6 and interleukin-b receptor (IL-6R) by means
      of fluorescence-correlation spectroscopy. For the first time we have succeeded in
      recapitulating in a cell-free condition the binding affinities and dynamics of IL
      6 and IL-6R to the gp130 receptor proteins, which have been determined on whole
      cells. Our results demonstrate that a dimer of gp130 first binds one IL-6/IL-6R
      complex and only at higher ligand concentrations does it bind a second IL-6/IL-6R
      complex. This view contrasts with the current perception of IL-6 receptor
      activation and reveals an alternative receptor activation mechanism.

PMID- 15722455
TI  - Sex-dependent expression and activity of the ATP-binding cassette transporter
      breast cancer resistance protein (BCRP/ABCG2) in liver.
AB  - The breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette drug
      efflux transporter present in the liver and other tissues that affects the
      pharmacological behavior of many compounds. To assess the possible role of BCRP
      in sex-dependent pharmacokinetics, we studied the in vivo disposition of several
      murine Bcrp1 substrates in male and female wild-type and Bcrp1 knockout mice.
      After oral administration of the antibiotic nitrofurantoin, the area under the
      plasma concentration-time curve in wild-type female mice was approximately 2-fold
      higher than in wild-type male mice. Moreover, after i.v. administration of
      nitrofurantoin, the antiulcerative cimetidine, the anticancer drug topotecan, and
      the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the plasma
      levels in wild-type female mice were all significantly higher than those in wild
      type male mice. Analysis of the expression of murine Bcrp1 in several
      pharmacokinetically important tissues showed that only the hepatic Bcrp1
      expression was higher in male mice compared with female mice. In line with this
      difference, the hepatobiliary excretion for nitrofurantoin and PhIP was,
      respectively, 9-fold higher and approximately 2-fold higher in male compared with
      female wild-type mice. No significant sex differences were observed in plasma
      levels or hepatobiliary excretion for any of the tested compounds in Bcrp1-/-
      mice, indicating that Bcrp1 was the main cause of the sex difference in wild-type
      mice. Analysis of hepatic expression of human BCRP also indicated a higher
      expression in men compared with women. In conclusion, sex-dependent expression of
      BCRP/Bcrp1 in the liver may be a cause of sex-specific variability in the
      pharmacokinetics of BCRP substrates, with potential impact on the clinical
      therapeutic applications and toxicity risks of drugs.

PMID- 15722456
TI  - Aspects of dioxin toxicity are mediated by interleukin 1-like cytokines.
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) results in a broad
      spectrum of toxic effects. Most, if not all, of these responses are dependent
      upon the binding of dioxin to the aryl hydrocarbon receptor. Given their common
      roles in chemically induced toxicity, we asked whether interleukin 1 (IL1)-like
      cytokines play a role in acute aspects of the dioxin response. To test this idea,
      we employed a "triple-null" mouse model that lacks the two receptors for the
      tumor necrosis factors-alpha and -beta and the receptor for the IL1-alpha and IL1
      beta cytokines. When triple null mice were treated with dioxin, there was
      significant attenuation in the levels of serum alanine aminotransferase,
      signifying reduced hepatocellular damage. In addition, the triple-null mice were
      protected from dioxin-induced liver inflammation. Loss of receptors for the IL1
      like cytokines was not protective for all aspects of dioxin toxicity. Endpoints
      such as thymic involution, Cyp1a2 induction, hepatomegaly, and hydropic
      degeneration remain unchanged in this model.

PMID- 15722457
TI  - Phenylglycine and sulfonamide correctors of defective delta F508 and G551D cystic
      fibrosis transmembrane conductance regulator chloride-channel gating.
AB  - Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
      chloride channel cause cystic fibrosis. The delta F508 mutation produces defects
      in channel gating and cellular processing, whereas the G551D mutation produces
      primarily a gating defect. To identify correctors of gating, 50,000 diverse small
      molecules were screened at 2.5 microM (with forskolin, 20 microM) by an iodide
      uptake assay in epithelial cells coexpressing delta F508-CFTR and a fluorescent
      halide indicator (yellow fluorescent protein-H148Q/I152L) after delta F508-CFTR
      rescue by 24-h culture at 27 degrees C. Secondary analysis and testing of >1000
      structural analogs yielded two novel classes of correctors of defective delta
      F508-CFTR gating ("potentiators") with nanomolar potency that were active in
      human delta F508 and G551D cells. The most potent compound of the phenylglycine
      class, 2-[(2-1H-indol-3-yl-acetyl)-methylamino]-N-(4-isopropylphenyl)-2
      phenylacetamide, reversibly activated delta F508-CFTR in the presence of
      forskolin with K(a) approximately 70 nM and also activated the CFTR gating
      mutants G551D and G1349D with K(a) values of approximately 1100 and 40 nM,
      respectively. The most potent sulfonamide, 6-(ethylphenylsulfamoyl)-4-oxo-1,4
      dihydroquinoline-3-carboxylic acid cycloheptylamide, had K(a) approximately 20 nM
      for activation of delta F508-CFTR. In cell-attached patch-clamp experiments,
      phenylglycine-01 (PG-01) and sulfonamide-01 (SF-01) increased channel open
      probability >5-fold by the reduction of interburst closed time. An interesting
      property of these compounds was their ability to act in synergy with cAMP
      agonists. Microsome metabolism studies and rat pharmacokinetic analysis suggested
      significantly more rapid metabolism of PG-01 than SF-03. Phenylglycine and
      sulfonamide compounds may be useful for monotherapy of cystic fibrosis caused by
      gating mutants and possibly for a subset of delta F508 subjects with significant
      delta F508-CFTR plasma-membrane expression.

PMID- 15722458
TI  - A natural CYP2B6 TATA box polymorphism (-82T--> C) leading to enhanced
      transcription and relocation of the transcriptional start site.
AB  - We investigated the impact of promoter polymorphisms on transcription of the
      human CYP2B6 gene. In total, 98 DNA samples from white persons from a previously
      characterized liver bank were sequenced throughout 2.3 kilobases of upstream
      sequence and haplotype structures were determined using additional coding
      sequence information. HepG2 cells and primary rat and human hepatocytes were
      transfected with luciferase reporter gene constructs driven by 2033 base pairs
      (bp) of the most frequent promoter variants. The novel haplotype *22 (-1848C-->
      A, -801G--> T, -750T--> C, and -82T--> C) showed 3- to 9-fold enhanced
      transcriptional activity in all transfected cells. Constructs containing single
      mutations surprisingly revealed -82T--> C, predicted to disrupt a putative TATA
      box, to be alone responsible for this effect. In silico analysis and
      electrophoretic mobility shift assay demonstrated conversion of the putative TATA
      box into a functional CCAAT/enhancer-binding protein binding site. Analysis of
      transcriptional start sites showed the mutant promoter to be transcribed from a
      start site located approximately 30 bp downstream of the wild-type start site,
      consistent with the use of a noncanonical TATA box at -55 bp. Median CYP2B6 mRNA
      expression and bupropion hydroxylase activity as a selective marker of CYP2B6
      catalytic activity were approximately 2-fold higher in livers genotyped -82TC as
      in those genotyped -82TT (20.4 versus 9.8 arbitrary units, p = 0.007, and 201.8
      versus 106.7 pmol/mg/min, p = 0.042, respectively). This promoter polymorphism
      thus contributes to CYP2B6 functional variability and represents a novel
      mechanism by which mutations can enhance transcription. Furthermore, a detailed
      interspecies comparison of CYP2B promoters and transcriptional start sites
      provided novel insights into evolutionary relationships.

PMID- 15722459
TI  - Developmental regulation of beta-carboline-induced inhibition of glycine-evoked
      responses depends on glycine receptor beta subunit expression.
AB  - In this work, we show that beta-carbolines, which are known negative allosteric
      modulators of GABA(A) receptors, inhibit glycine-induced currents of embryonic
      mouse spinal cord and hippocampal neurons. In both cell types, beta-carboline
      induced inhibition of glycine receptor (GlyR)-mediated responses decreases with
      time in culture. Single-channel recordings show that the major conductance levels
      of GlyR unitary currents shifts from high levels (> or = 50 pS) in 2 to 3 days in
      vitro (DIV) neurons to low levels (<50 pS) in 11 to 14 DIV neurons, assessing the
      replacement of functional homomeric GlyR by heteromeric GlyR. In cultured spinal
      cord neurons, the disappearance of beta-carboline inhibition of glycine responses
      and high conductance levels is almost complete in mature neurons, whereas a
      weaker decrease in beta-carboline-evoked glycine response inhibition and high
      conductance level proportion is observed in hippocampal neurons. To confirm the
      hypothesis that the decreased sensitivity of GlyR to beta-carbolines depends on
      beta subunit expression, Chinese hamster ovary cells were permanently transfected
      either with GlyR alpha2 subunit alone or in combination with GlyR beta subunit.
      Single-channel recordings revealed that the major conductance levels shifted from
      high levels (> or = 50 pS) in GlyR-alpha2-transfected cells to low levels (<50
      pS) in GlyR-alpha2+beta-containing cells. Consistently, both picrotoxin- and beta
      carboline-induced inhibition of glycine-gated currents were significantly
      decreased in GlyR-alpha2+beta-transfected cells compared with GlyR-alpha2
      containing cells. In summary, we demonstrate that the incorporation of beta
      subunits in GlyRs confers resistance not only to picrotoxin but also to beta
      carboline-induced inhibition. Furthermore, we also provide evidence that
      hippocampal neurons undergo in vitro a partial maturation process of their GlyR
      mediated responses.

PMID- 15722460
TI  - Natural medicine: a 'new frontier' in oncology?

PMID- 15722461
TI  - How little is known about cervical cancer in pregnancy?

PMID- 15722463
TI  - BASIC PENTACYSTEINE1, a GA binding protein that induces conformational changes in
      the regulatory region of the homeotic Arabidopsis gene SEEDSTICK.
AB  - The mechanisms for the regulation of homeotic genes are poorly understood in most
      organisms, including plants. We identified BASIC PENTACYSTEINE1 (BPC1) as a
      regulator of the homeotic Arabidopsis thaliana gene SEEDSTICK (STK), which
      controls ovule identity, and characterized its mechanism of action. A combination
      of tethered particle motion analysis and electromobility shift assays revealed
      that BPC1 is able to induce conformational changes by cooperative binding to
      purine-rich elements present in the STK regulatory sequence. Analysis of STK
      expression in the bpc1 mutant showed that STK is upregulated. Our results give
      insight into the regulation of gene expression in plants and provide the basis
      for further studies to understand the mechanisms that control ovule identity in
      Arabidopsis.

PMID- 15722464
TI  - Dissecting the beta-aminobutyric acid-induced priming phenomenon in Arabidopsis.
AB  - Plants treated with the nonprotein amino acid beta-aminobutyric acid (BABA)
      develop an enhanced capacity to resist biotic and abiotic stresses. This BABA
      induced resistance (BABA-IR) is associated with an augmented capacity to express
      basal defense responses, a phenomenon known as priming. Based on the observation
      that high amounts of BABA induce sterility in Arabidopsis thaliana, a mutagenesis
      screen was performed to select mutants impaired in BABA-induced sterility (ibs).
      Here, we report the isolation and subsequent characterization of three T-DNA
      tagged ibs mutants. Mutant ibs1 is affected in a cyclin-dependent kinase-like
      protein, and ibs2 is defective in AtSAC1b encoding a polyphosphoinositide
      phosphatase. Mutant ibs3 is affected in the regulation of the ABA1 gene encoding
      the abscisic acid (ABA) biosynthetic enzyme zeaxanthin epoxidase. To elucidate
      the function of the three IBS genes in plant resistance, the mutants were tested
      for BABA-IR against the bacterium Pseudomonas syringae pv tomato, the oomycete
      Hyaloperonospora parasitica, and BABA-induced tolerance to salt. All three ibs
      mutants were compromised in BABA-IR against H. parasitica, although to a
      different extent. Whereas ibs1 was reduced in priming for salicylate (SA)
      dependent trailing necrosis, mutants ibs2 and ibs3 were affected in the priming
      for callose deposition. Only ibs1 failed to express BABA-IR against P. syringae,
      which coincided with a defect in priming for SA-inducible PR-1 gene expression.
      By contrast, ibs2 and ibs3 showed reduced BABA-induced tolerance to salt, which
      correlated with an affected priming for ABA-inducible gene expression. For all
      three ibs alleles, the defects in BABA-induced sterility and BABA-induced
      protection against P. syringae, H. parasitica, and salt could be confirmed in
      independent mutants. The data presented here introduce three novel regulatory
      genes involved in priming for different defense responses.

PMID- 15722465
TI  - Identification and dynamics of two classes of aurora-like kinases in Arabidopsis
      and other plants.
AB  - Aurora-like kinases play key roles in chromosome segregation and cytokinesis in
      yeast, plant, and animal systems. Here, we characterize three Arabidopsis
      thaliana protein kinases, designated AtAurora1, AtAurora2, and AtAurora3, which
      share high amino acid identities with the Ser/Thr kinase domain of yeast Ipl1 and
      animal Auroras. Structure and expression of AtAurora1 and AtAurora2 suggest that
      these genes arose by a recent gene duplication, whereas the diversification of
      plant alpha and beta Aurora kinases predates the origin of land plants. The
      transcripts and proteins of all three kinases are most abundant in tissues
      containing dividing cells. Intracellular localization of green fluorescent
      protein-tagged AtAuroras revealed an AtAurora-type specific association mainly
      with dynamic mitotic structures, such as microtubule spindles and centromeres,
      and with the emerging cell plate of dividing tobacco (Nicotiana tabacum) BY-2
      cells. Immunolabeling using AtAurora antibodies yielded specific signals at the
      centromeres that are coincident with histone H3 that is phosphorylated at Ser
      position10 during mitosis. An in vitro kinase assay demonstrated that AtAurora1
      preferentially phosphorylates histone H3 at Ser 10 but not at Ser 28 or Thr 3,
      11, and 32. The phylogenetic analysis of available Aurora sequences from
      different eukaryotic origins suggests that, although a plant Aurora gene has been
      duplicated early in the evolution of plants, the paralogs nevertheless maintained
      a role in cell cycle-related signal transduction pathways.

PMID- 15722466
TI  - Comparisons of maize pericarp color1 alleles reveal paralogous gene recombination
      and an organ-specific enhancer region.
AB  - The maize (Zea mays) p1 (for pericarp color1) gene encodes an R2R3 Myb-like
      transcription factor that regulates the flavonoid biosynthetic pathway in floral
      organs, most notably kernel pericarp and cob. Alleles of the p1 gene condition
      distinct tissue-specific pigmentation patterns; to elucidate the molecular basis
      of these allele-specific expression patterns, we characterized two novel P1-rw
      (for red pericarp/white cob) alleles, P1-rw1077 and P1-rw751Ac. Structural
      analysis of P1-rw1077 indicated that this allele was generated by recombination
      between p1 and the tightly linked paralogous gene, p2. In the resulting gene, the
      p1 coding sequence was replaced by the p2 coding sequence, whereas the flanking
      p1 regulatory sequences remained largely preserved. The red pericarp color
      specified by P1-rw1077 suggests that the p1- and p2-encoded proteins are
      functionally equivalent as regulatory factors in the flavonoid biosynthesis
      pathway. Sequence analysis shows that the P1-rw1077 allele lacks a 386-bp
      sequence in a distal enhancer region 5 kb upstream of the transcription start
      site. An independently derived P1-rw allele contains an Ac insertion into the
      same sequence, indicating that this site likely contains cob glume-specific
      regulatory elements.

PMID- 15722467
TI  - The cotton ACTIN1 gene is functionally expressed in fibers and participates in
      fiber elongation.
AB  - Single-celled cotton fiber (Gossypium hirsutum) provides a unique experimental
      system to study cell elongation. To investigate the role of the actin
      cytoskeleton during fiber development, 15 G. hirsutum ACTIN (GhACT) cDNA clones
      were characterized. RNA gel blot and real-time RT-PCR analysis revealed that
      GhACT genes are differentially expressed in different tissues and can be
      classified into four groups. One group, represented by GhACT1, is expressed
      predominantly in fiber cells and was studied in detail. A 0.8-kb GhACT1 promoter
      sufficient to confirm its fiber-specific expression was identified. RNA
      interference of GhACT1 caused significant reduction of its mRNA and protein
      levels and disrupted the actin cytoskeleton network in fibers. No defined actin
      network was observed in these fibers and, consequently, fiber elongation was
      inhibited. Our results suggested that GhACT1 plays an important role in fiber
      elongation but not fiber initiation.

PMID- 15722468
TI  - The Arabidopsis plastidic glucose 6-phosphate/phosphate translocator GPT1 is
      essential for pollen maturation and embryo sac development.
AB  - Plastids of nongreen tissues can import carbon in the form of glucose 6-phosphate
      via the glucose 6-phosphate/phosphate translocator (GPT). The Arabidopsis
      thaliana genome contains two homologous GPT genes, AtGPT1 and AtGPT2. Both
      proteins show glucose 6-phosphate translocator activity after reconstitution in
      liposomes, and each of them can rescue the low-starch leaf phenotype of the pgi1
      mutant (which lacks plastid phosphoglucoisomerase), indicating that the two
      proteins are also functional in planta. AtGPT1 transcripts are ubiquitously
      expressed during plant development, with highest expression in stamens, whereas
      AtGPT2 expression is restricted to a few tissues, including senescing leaves.
      Disruption of GPT2 has no obvious effect on growth and development under
      greenhouse conditions, whereas the mutations gpt1-1 and gpt1-2 are lethal. In
      both gpt1 lines, distorted segregation ratios, reduced efficiency of transmission
      in males and females, and inability to complete pollen and ovule development were
      observed, indicating profound defects in gametogenesis. Embryo sac development is
      arrested in the gpt1 mutants at a stage before the fusion of the polar nuclei.
      Mutant pollen development is associated with reduced formation of lipid bodies
      and small vesicles and the disappearance of dispersed vacuoles, which results in
      disintegration of the pollen structure. Taken together, our results indicate that
      GPT1-mediated import of glucose 6-phosphate into nongreen plastids is crucial for
      gametophyte development. We suggest that loss of GPT1 function results in
      disruption of the oxidative pentose phosphate cycle, which in turn affects fatty
      acid biosynthesis.

PMID- 15722470
TI  - Structural basis for the interaction between pectin methylesterase and a specific
      inhibitor protein.
AB  - Pectin, one of the main components of the plant cell wall, is secreted in a
      highly methyl-esterified form and subsequently deesterified in muro by pectin
      methylesterases (PMEs). In many developmental processes, PMEs are regulated by
      either differential expression or posttranslational control by protein inhibitors
      (PMEIs). PMEIs are typically active against plant PMEs and ineffective against
      microbial enzymes. Here, we describe the three-dimensional structure of the
      complex between the most abundant PME isoform from tomato fruit (Lycopersicon
      esculentum) and PMEI from kiwi (Actinidia deliciosa) at 1.9-A resolution. The
      enzyme folds into a right-handed parallel beta-helical structure typical of
      pectic enzymes. The inhibitor is almost all helical, with four long alpha-helices
      aligned in an antiparallel manner in a classical up-and-down four-helical bundle.
      The two proteins form a stoichiometric 1:1 complex in which the inhibitor covers
      the shallow cleft of the enzyme where the putative active site is located. The
      four-helix bundle of the inhibitor packs roughly perpendicular to the main axis
      of the parallel beta-helix of PME, and three helices of the bundle interact with
      the enzyme. The interaction interface displays a polar character, typical of
      nonobligate complexes formed by soluble proteins. The structure of the complex
      gives an insight into the specificity of the inhibitor toward plant PMEs and the
      mechanism of regulation of these enzymes.

PMID- 15722469
TI  - Role of beta-oxidation in jasmonate biosynthesis and systemic wound signaling in
      tomato.
AB  - Jasmonic acid (JA) is a lipid-derived signal that regulates plant defense
      responses to biotic stress. Here, we report the characterization of a JA
      deficient mutant of tomato (Lycopersicon esculentum) that lacks local and
      systemic expression of defensive proteinase inhibitors (PIs) in response to
      wounding. Map-based cloning studies demonstrated that this phenotype results from
      loss of function of an acyl-CoA oxidase (ACX1A) that catalyzes the first step in
      the peroxisomal beta-oxidation stage of JA biosynthesis. Recombinant ACX1A
      exhibited a preference for C12 and C14 straight-chain acyl-CoAs and also was
      active in the metabolism of C18 cyclopentanoid-CoA precursors of JA. The overall
      growth, development, and reproduction of acx1 plants were similar to wild-type
      plants. However, the mutant was compromised in its defense against tobacco
      hornworm (Manduca sexta) attack. Grafting experiments showed that loss of ACX1A
      function disrupts the production of the transmissible signal for wound-induced PI
      expression but does not affect the recognition of this signal in undamaged
      responding leaves. We conclude that ACX1A is essential for the beta-oxidation
      stage of JA biosynthesis and that JA or its derivatives is required both for
      antiherbivore resistance and the production of the systemic wound signal. These
      findings support a role for peroxisomes in the production of lipid-based
      signaling molecules that promote systemic defense responses.

PMID- 15722471
TI  - Actin filaments play a critical role in vacuolar trafficking at the Golgi complex
      in plant cells.
AB  - Actin filaments are thought to play an important role in intracellular
      trafficking in various eukaryotic cells. However, their involvement in
      intracellular trafficking in plant cells has not been clearly demonstrated. Here,
      we investigated the roles actin filaments play in intracellular trafficking in
      plant cells using latrunculin B (Lat B), an inhibitor of actin filament assembly,
      or actin mutants that disrupt actin filaments when overexpressed. Lat B and
      actin2 mutant overexpression inhibited the trafficking of two vacuolar reporter
      proteins, sporamin:green fluorescent protein (GFP) and Arabidopsis thaliana
      aleurain-like protein:GFP, to the central vacuole; instead, a punctate staining
      pattern was observed. Colocalization experiments with various marker proteins
      indicated that these punctate stains corresponded to the Golgi complex. The A.
      thaliana vacuolar sorting receptor VSR-At, which mainly localizes to the
      prevacuolar compartment, also accumulated at the Golgi complex in the presence of
      Lat B. However, Lat B had no effect on the endoplasmic reticulum (ER) to Golgi
      trafficking of sialyltransferase or retrograde Golgi to ER trafficking. Lat B
      also failed to influence the Golgi to plasma membrane trafficking of H+
      ATPase:GFP or the secretion of invertase:GFP. Based on these observations, we
      propose that actin filaments play a critical role in the trafficking of proteins
      from the Golgi complex to the central vacuole.

PMID- 15722472
TI  - RIN13 is a positive regulator of the plant disease resistance protein RPM1.
AB  - The RPM1 protein confers resistance to Pseudomonas syringae pv tomato DC3000
      expressing either of the Type III effector proteins AvrRpm1 or AvrB. Here, we
      describe the isolation and functional characterization of RPM1 Interacting
      Protein 13 (RIN13), a resistance protein interactor shown to positively enhance
      resistance function. Ectopic expression of RIN13 (RIN13s) enhanced bacterial
      restriction mechanisms but paradoxically abolished the normally rapid
      hypersensitive response (HR) controlled by RPM1. In contrast with wild-type
      plants, leaves expressing RIN13s did not undergo electrolyte leakage or
      accumulate H2O2 after bacterial delivery of AvrRpm1. Overexpression of RIN13 also
      altered the transcription profile observed during a normal HR. By contrast, RIN13
      knockout plants had the same ion leakage signatures and HR timing of wild-type
      plants in response to DC3000(avrRpm1) but failed to suppress bacterial growth.
      The modified phenotypes seen in the RIN13s/as plants were specific to recognition
      of AvrRpm1 or AvrB, and wild-type responses were observed after challenge with
      other incompatible pathogens or the virulent DC3000 isolate. Our results suggest
      that cell death is not necessary to confer resistance, and engineering enhanced
      resistance without activation of programmed cell death is a real possibility.

PMID- 15722473
TI  - Cell type-specific localization of transcripts encoding nine consecutive enzymes
      involved in protoberberine alkaloid biosynthesis.
AB  - Molecular clones encoding nine consecutive biosynthetic enzymes that catalyze the
      conversion of l-dopa to the protoberberine alkaloid (S)-canadine were isolated
      from meadow rue (Thalictrum flavum ssp glaucum). The predicted proteins showed
      extensive sequence identity with corresponding enzymes involved in the
      biosynthesis of related benzylisoquinoline alkaloids in other species, such as
      opium poppy (Papaver somniferum). RNA gel blot hybridization analysis showed that
      gene transcripts for each enzyme were most abundant in rhizomes but were also
      detected at lower levels in roots and other organs. In situ RNA hybridization
      analysis revealed the cell type-specific expression of protoberberine alkaloid
      biosynthetic genes in roots and rhizomes. In roots, gene transcripts for all nine
      enzymes were localized to immature endodermis, pericycle, and, in some cases,
      adjacent cortical cells. In rhizomes, gene transcripts encoding all nine enzymes
      were restricted to the protoderm of leaf primordia. The localization of
      biosynthetic gene transcripts was in contrast with the tissue-specific
      accumulation of protoberberine alkaloids. In roots, protoberberine alkaloids were
      restricted to mature endodermal cells upon the initiation of secondary growth and
      were distributed throughout the pith and cortex in rhizomes. Thus, the cell type
      specific localization of protoberberine alkaloid biosynthesis and accumulation
      are temporally and spatially separated in T. flavum roots and rhizomes,
      respectively. Despite the close phylogeny between corresponding biosynthetic
      enzymes, distinct and different cell types are involved in the biosynthesis and
      accumulation of benzylisoquinoline alkaloids in T. flavum and P. somniferum. Our
      results suggest that the evolution of alkaloid metabolism involves not only the
      recruitment of new biosynthetic enzymes, but also the migration of established
      pathways between cell types.

PMID- 15722474
TI  - Structure-function analysis of cf-9, a receptor-like protein with
      extracytoplasmic leucine-rich repeats.
AB  - The tomato (Lycopersicon pimpinellifolium) resistance protein Cf-9 belongs to a
      large class of plant proteins with extracytoplasmic Leu-rich repeats (eLRRs).
      eLRR proteins play key roles in plant defense and development, mainly as receptor
      like proteins or receptor-like kinases, conferring recognition of various
      pathogen molecules and plant hormones. We report here a large-scale structure
      function analysis of an eLRR protein. A total of 66 site-directed mutants of Cf-9
      were analyzed for activity in Avr9 recognition and for protein stability and the
      results interpreted with the help of a homology model of the Cf-9 structure.
      Conserved Trp and Cys pairs in the N-terminal LRR-flanking domain appear to be
      important for Cf-9 activity and are probably exposed at the putative concave
      inner surface of the Cf-9 protein, where recognition specificity also resides.
      Removal of each of the 22 putative N-linked glycosylation sites (PGS) revealed
      that many PGSs contribute to Cf-9 activity and that the PGSs in the putative
      alpha-helices of the LRR modules are essential. Immunoblot analysis and mass
      spectrometry showed that all but one of the PGSs are N-glycosylated. Introduction
      of glycosylation at the putative concave beta-sheet surface blocks Cf-9 activity,
      in some cases probably by disturbing specific recognition, and in another case by
      steric hindrance with existing N-glycans. The glycosylation pattern and several
      other features are conserved in other eLRR proteins, where similar mutations show
      similar phenotypes.

PMID- 15722475
TI  - The Arabidopsis GAMYB-like genes, MYB33 and MYB65, are microRNA-regulated genes
      that redundantly facilitate anther development.
AB  - The functions of the vast majority of genes encoding R2R3 MYB domain proteins
      remain unknown. The closely related MYB33 and MYB65 genes of Arabidopsis thaliana
      have high sequence similarity to the barley (Hordeum vulgare) GAMYB gene. T-DNA
      insertional mutants were isolated for both genes, and a myb33 myb65 double mutant
      was defective in anther development. In myb33 myb65 anthers, the tapetum
      undergoes hypertrophy at the pollen mother cell stage, resulting in premeiotic
      abortion of pollen development. However, myb33 myb65 sterility was conditional,
      where fertility increased both under higher light or lower temperature
      conditions. Thus, MYB33/MYB65 facilitate, but are not essential for, anther
      development. Neither single mutant displayed a phenotype, implying that MYB33 and
      MYB65 are functionally redundant. Consistent with functional redundancy, promoter
      beta-glucuronidase (GUS) fusions of MYB33 and MYB65 gave identical expression
      patterns in flowers (sepals, style, receptacle, anther filaments, and connective
      but not in anthers themselves), shoot apices, and root tips. By contrast,
      expression of a MYB33:GUS translational fusion in flowers was solely in young
      anthers (consistent with the male sterile phenotype), and no staining was seen in
      shoot meristems or root tips. A microRNA target sequence is present in the MYB
      genes, and mutating this sequence in the MYB33:GUS fusion results in an expanded
      expression pattern, in tissues similar to that observed in the promoter-GUS
      lines, implying that the microRNA target sequence is restricting MYB33
      expression. Arabidopsis transformed with MYB33 containing the mutated microRNA
      target had dramatic pleiotrophic developmental defects, suggesting that
      restricting MYB33 expression, especially in the shoot apices, is essential for
      proper plant development.

PMID- 15722477
TI  - A sequence-based identification of the genes detected by probesets on the
      Affymetrix U133 plus 2.0 array.
AB  - One of the biggest problems facing microarray experiments is the difficulty of
      translating results into other microarray formats or comparing microarray results
      to other biochemical methods. We believe that this is largely the result of poor
      gene identification. We re-identified the probesets on the Affymetrix U133 plus
      2.0 GeneChip array. This identification was based on the sequence of the probes
      and the sequence of the human genome. Using the BLAST program, we matched probes
      with documented and postulated human transcripts. This resulted in the
      redefinition of approximately 37% of the probes on the U133 plus 2.0 array. This
      updated identification specifically points out where the identification is
      complicated by cross-hybridization from splice variants or closely related genes.
      More than 5000 probesets detect multiple transcripts and therefore the exact
      protein affected cannot be readily concluded from the performance of one probeset
      alone. This makes naming difficult and impacts any downstream analysis such as
      associating gene ontologies, mapping affected pathways or simply validating
      expression changes. We have now automated the sequence-based identification and
      can more appropriately annotate any array where the sequence on each spot is
      known.

PMID- 15722476
TI  - siRNA target site secondary structure predictions using local stable
      substructures.
AB  - The crystal structure based model of the catalytic center of Ago2 revealed that
      the siRNA and the mRNA must be able to form an A-helix for correct positing of
      the scissile phosphate bond for cleavage in RNAi. This suggests that base pairing
      of the target mRNA with itself, i.e. secondary structure, must be removed before
      cleavage. Early on in the siRNA design, GC-rich target sites were avoided because
      of their potential to be involved in strong secondary structure. It is still
      unclear how important a factor mRNA secondary structure is in RNAi. However, it
      has been established that a difference in the thermostability of the ends of an
      siRNA duplex dictate which strand is loaded into the RNA-induced silencing
      complex. Here, we use a novel secondary structure prediction method and duplex
      end differential calculations to investigate the importance of a secondary
      structure in the siRNA design. We found that the differential duplex-end
      stabilities alone account for functional prediction of 60% of the 80 siRNA sites
      examined, and that secondary structure predictions improve the prediction of site
      efficacy. A total of 80% of the non-functional sites can be eliminated using
      secondary structure predictions and duplex-end differential.

PMID- 15722478
TI  - Discovery of active proteins directly from combinatorial randomized protein
      libraries without display, purification or sequencing: identification of novel
      zinc finger proteins.
AB  - We have successfully linked protein library screening directly with the
      identification of active proteins, without the need for individual purification,
      display technologies or physical linkage between the protein and its encoding
      sequence. By using 'MAX' randomization we have rapidly constructed 60 overlapping
      gene libraries that encode zinc finger proteins, randomized variously at the
      three principal DNA-contacting residues. Expression and screening of the
      libraries against five possible target DNA sequences generated data points
      covering a potential 40,000 individual interactions. Comparative analysis of the
      resulting data enabled direct identification of active proteins. Accuracy of this
      library analysis methodology was confirmed by both in vitro and in vivo analyses
      of identified proteins to yield novel zinc finger proteins that bind to their
      target sequences with high affinity, as indicated by low nanomolar apparent
      dissociation constants.

PMID- 15722480
TI  - Investigation of Mg2+- and temperature-dependent folding of the hairpin ribozyme
      by photo-crosslinking: effects of photo-crosslinker tether length and chemistry.
AB  - We have used photo-crosslinking to investigate the structure and dynamics of four
      way junction hairpin ribozyme constructs. Four phenylazide photo-crosslinkers
      were coupled to 2'-NH2-modified U+2 in the substrate and irradiated at different
      Mg2+ concentrations and temperatures. Consistent with the role of divalent metal
      ions in hairpin ribozyme folding, we observed more interdomain crosslinks in the
      presence of Mg2+ than in its absence. In general, we observed intradomain
      crosslinks to nucleotides 2-11 and interdomain crosslinks to the U1A binding
      loop. Crosslinks to A26 and G36 in domain B were also observed when crosslinking
      was carried out at -78 degrees C. In contrast to crosslinking results at higher
      temperatures (0, 25 and 37 degrees C), similar crosslinks were obtained in the
      presence and absence of Mg2+ at -78 degrees C, suggesting Mg2+ stabilizes a low
      energy hairpin ribozyme conformation. We also evaluated the effects of photo
      crosslinker structure and mechanism on crosslinks. First, most crosslinks were to
      unpaired nucleotides. Second, shorter and longer photo-crosslinkers formed
      crosslinks to intradomain locations nearer to and farther from photo-crosslinker
      modification, respectively. Finally, fluorine substitutions on the phenylazide
      ring did not change the locations of crosslinks, but rather decreased
      crosslinking efficiency. These findings have implications for the use of
      phenylazide photo-crosslinkers in structural studies of RNA.

PMID- 15722479
TI  - Comparisons of substitution, insertion and deletion probes for resequencing and
      mutational analysis using oligonucleotide microarrays.
AB  - Although oligonucleotide probes complementary to single nucleotide substitutions
      are commonly used in microarray-based screens for genetic variation, little is
      known about the hybridization properties of probes complementary to small
      insertions and deletions. It is necessary to define the hybridization properties
      of these latter probes in order to improve the specificity and sensitivity of
      oligonucleotide microarray-based mutational analysis of disease-related genes.
      Here, we compare and contrast the hybridization properties of oligonucleotide
      microarrays consisting of 25mer probes complementary to all possible single
      nucleotide substitutions and insertions, and one and two base deletions in the
      9168 bp coding region of the ATM (ataxia telangiectasia mutated) gene. Over 68
      different dye-labeled single-stranded nucleic acid targets representing all ATM
      coding exons were applied to these microarrays. We assess hybridization
      specificity by comparing the relative hybridization signals from probes perfectly
      matched to ATM sequences to those containing mismatches. Probes complementary to
      two base substitutions displayed the highest average specificity followed by
      those complementary to single base substitutions, single base deletions and
      single base insertions. In all the cases, hybridization specificity was strongly
      influenced by sequence context and possible intra- and intermolecular probe
      and/or target structure. Furthermore, single nucleotide substitution probes
      displayed the most consistent hybridization specificity data followed by single
      base deletions, two base deletions and single nucleotide insertions. Overall,
      these studies provide valuable empirical data that can be used to more accurately
      model the hybridization properties of insertion and deletion probes and improve
      the design and interpretation of oligonucleotide microarray-based resequencing
      and mutational analysis.

PMID- 15722481
TI  - Plant promoter prediction with confidence estimation.
AB  - Accurate prediction of promoters is fundamental to understanding gene expression
      patterns, where confidence estimation is one of the main requirements. Using
      recently developed transductive confidence machine (TCM) techniques, we developed
      a new program TSSP-TCM for the prediction of plant promoters that also provides
      confidence of the prediction. The program was trained on 132 and 104 sequences
      and tested on 40 and 25 sequences (containing TATA and TATA-less promoters,
      respectively) with known transcription start sites (TSSs). As negative training
      samples for TCM learning we used coding and intron sequences of plant genes
      annotated in the GenBank. In the test set of TATA promoters, the program
      correctly predicted TSS for 35 out of 40 (87.5%) genes with a median deviation of
      several base pairs from the true site location. For 25 TATA-less promoters, TSSs
      were predicted for 21 out of 25 (84%) genes, including 14 cases of 5 bp distance
      between annotated and predicted TSSs. Using TSSP-TCM program we annotated
      promoters in the whole Arabidopsis genome. The predicted promoters were in good
      agreement with the start position of known Arabidopsis mRNAs. Thus, TCM technique
      has produced a plant-oriented promoter prediction tool of high accuracy. TSSP-TCM
      program and annotated promoters are available at
      http://mendel.cs.rhul.ac.uk/mendel.php?topic=fgen.

PMID- 15722482
TI  - The mouse RNase 4 and RNase 5/ang 1 locus utilizes dual promoters for tissue
      specific expression.
AB  - The ribonuclease A (RNase A) superfamily has been the subject of extensive
      studies in the areas of protein evolution, structure and biochemistry and are
      exciting molecules in that they appear to be responding to unique selection
      pressures, generating proteins capable of multiple and diverse activities. The
      RNase 4 and RNase 5/ang 1 shared locus breaks a pattern that is otherwise
      canonical among the members of the RNase A gene superfamily. Conserved among
      humans, mice and rats, the locus includes two non-coding exons followed by two
      distinct exons encoding RNase 4 and RNase 5/ang 1. Transcription from this locus
      is controlled by differential splicing and tissue-specific expression from
      promoters located 5' to each of the non-coding exons. Promoter 1, 5' to exon I,
      is universally active, while Promoter 2, 5' to exon II, is active only in hepatic
      cells in promoter assays in vitro. Transcription from Promoter 2 is dependent on
      an intact HNF-1 consensus binding site which binds the transcription factor HNF
      1alpha. In summary, RNase 4 and RNase 5/ang 1 are unique among the RNase A
      ribonuclease genes in that they maintain a complex gene locus that is conserved
      across species with transcription initiated from tissue-specific dual promoters
      followed by differential exon splicing.

PMID- 15722483
TI  - Mutant p53 proteins bind DNA in a DNA structure-selective mode.
AB  - Despite the loss of sequence-specific DNA binding, mutant p53 (mutp53) proteins
      can induce or repress transcription of mutp53-specific target genes. To date, the
      molecular basis for transcriptional modulation by mutp53 is not understood, but
      increasing evidence points to the possibility that specific interactions of
      mutp53 with DNA play an important role. So far, the lack of a common denominator
      for mutp53 DNA binding, i.e. the existence of common sequence elements, has
      hampered further characterization of mutp53 DNA binding. Emanating from our
      previous discovery that DNA structure is an important determinant of wild-type
      p53 (wtp53) DNA binding, we analyzed the binding of various mutp53 proteins to
      oligonucleotides mimicking non-B DNA structures. Using various DNA-binding assays
      we show that mutp53 proteins bind selectively and with high affinity to non-B
      DNA. In contrast to sequence-specific and DNA structure-dependent binding of
      wtp53, mutp53 DNA binding to non-B DNA is solely dependent on the stereo-specific
      configuration of the DNA, and not on DNA sequence. We propose that DNA structure
      selective binding of mutp53 proteins is the basis for the well-documented
      interaction of mutp53 with MAR elements and for transcriptional activities
      mediates by mutp53.

PMID- 15722484
TI  - The SAF-box domain of chromatin protein DEK.
AB  - DEK is an abundant chromatin protein in metazoans reaching copy numbers of
      several millions/nucleus. Previous work has shown that human DEK, a protein of
      375 amino acids, has two functional DNA-binding domains, of which one resides in
      a central part of the molecule and contains sequences corresponding to the
      scaffold attachment factor-box (SAF-box) domain as found in a growing number of
      nuclear proteins. Isolated SAF-box peptides (amino acids 137-187) bind weakly to
      DNA in solution, but when many SAF-box peptides are brought into close proximity
      on the surface of Sephadex beads, cooperative effects lead to a high affinity to
      DNA. Furthermore, a peptide (amino acids 87-187) that includes a sequence on the
      N-terminal side of the SAF-box binds efficiently to DNA. This peptide prefers
      four-way junction DNA over straight DNA and induces supercoils in relaxed
      circular DNA just like the full-length DEK. Interestingly, however, the 87-187
      amino acid peptide introduces negative supercoils in contrast to the full-length
      DEK, which is known to introduce positive supercoils. We found that two adjacent
      regions (amino acids 68-87 and 187-250) are necessary for the formation of
      positive supercoils. Our data contribute to the ongoing characterization of the
      abundant and ubiquitous DEK chromatin protein.

PMID- 15722485
TI  - The unusually large Plasmodium telomerase reverse-transcriptase localizes in a
      discrete compartment associated with the nucleolus.
AB  - Telomerase replicates chromosome ends, a function necessary for maintaining
      genome integrity. We have identified the gene that encodes the catalytic reverse
      transcriptase (RT) component of this enzyme in the malaria parasite Plasmodium
      falciparum (PfTERT) as well as the orthologous genes from two rodent and one
      simian malaria species. PfTERT is predicted to encode a basic protein that
      contains the major sequence motifs previously identified in known telomerase RTs
      (TERTs). At approximately 2500 amino acids, PfTERT is three times larger than
      other characterized TERTs. We observed remarkable sequence diversity between TERT
      proteins of different Plasmodial species, with conserved domains alternating with
      hypervariable regions. Immunofluorescence analysis revealed that PfTERT is
      expressed in asexual blood stage parasites that have begun DNA synthesis.
      Surprisingly, rather than at telomere clusters, PfTERT typically localizes into a
      discrete nuclear compartment. We further demonstrate that this compartment is
      associated with the nucleolus, hereby defined for the first time in P.falciparum.

PMID- 15722486
TI  - Biochemical characterization and DNA repair pathway interactions of Mag1-mediated
      base excision repair in Schizosaccharomyces pombe.
AB  - The Schizosaccharomyces pombe mag1 gene encodes a DNA repair enzyme with sequence
      similarity to the AlkA family of DNA glycosylases, which are essential for the
      removal of cytotoxic alkylation products, the premutagenic deamination product
      hypoxanthine and certain cyclic ethenoadducts such as ethenoadenine. In this
      paper, we have purified the Mag1 protein and characterized its substrate
      specificity. It appears that the substrate range of Mag1 is limited to the major
      alkylation products, such as 3-mA, 3-mG and 7-mG, whereas no significant activity
      was found towards deamination products, ethenoadducts or oxidation products. The
      efficiency of 3-mA and 3-mG removal was 5-10 times slower for Mag1 than for
      Escherichia coli AlkA whereas the rate of 7-mG removal was similar to the two
      enzymes. The relatively low efficiency for the removal of cytotoxic 3
      methylpurines is consistent with the moderate sensitivity of the mag1 mutant to
      methylating agents. Furthermore, we studied the initial steps of Mag1-dependent
      base excision repair (BER) and genetic interactions with other repair pathways by
      mutant analysis. The double mutants mag1 nth1, mag1 apn2 and mag1 rad2 displayed
      increased resistance to methyl methanesulfonate (MMS) compared with the single
      mutants nth1, apn2 and rad2, respectively, indicating that Mag1 initiates both
      short-patch (Nth1-dependent) and long-patch (Rad2-dependent) BER of MMS-induced
      damage. Spontaneous intrachromosomal recombination frequencies increased 3-fold
      in the mag1 mutant suggesting that Mag1 and recombinational repair (RR) are both
      involved in repair of alkylated bases. Finally, we show that the deletion of mag1
      in the background of rad16, nth1 and rad2 single mutants reduced the total
      recombination frequencies of all three double mutants, indicating that abasic
      sites formed as a result of Mag1 removal of spontaneous base lesions are
      substrates for nucleotide excision repair, long- and short-patch BER and RR.

PMID- 15722488
TI  - 'Zef'.

PMID- 15722487
TI  - Functional characterization of the mitochondrial 12S rRNA C1494T mutation
      associated with aminoglycoside-induced and non-syndromic hearing loss.
AB  - In this study, we report the biochemical characterization of the deafness
      associated mitochondrial 12S rRNA C1494T mutation using 27 cybrid cell lines
      constructed by transferring mitochondria from 9 lymphoblastoid cell lines derived
      from a Chinese family into human mitochondrial DNA (mtDNA)-less (rho degrees)
      cells. Six cybrids derived from two asymptomatic members, and nine cybrids
      derived from three symptomatic members of the Chinese family carrying the C1494T
      mutation exhibited approximately 38 and 43% decrease in the rate of mitochondrial
      protein labeling, respectively, compared with twelve cybrids derived from four
      Chinese control individuals. These defects are apparently a primary contributor
      to significant reductions in the rate of overall respiratory capacity or the rate
      of malate/glutamate promoted respiration, or succinate/G3P-promoted respiration,
      or TMPD/ascorbate-promoted respiration in mutant cybrid cell lines derived from
      either symptomatic or asymptomatic individuals. Furthermore, the very
      significant/nearly identical increase in the ratio of doubling times in DMDM
      medium in the presence/absence of high concentration of paromomycin was observed
      in symptomatic or asymptomatic cybrid cell lines carrying the C1494T mutation as
      compared with the average rate in control cell lines. These observations provide
      the direct biochemical evidences that the C1494T mutation is a pathogenic mtDNA
      mutation associated with aminoglycoside-induced and non-syndromic hearing loss.
      In addition, these data provide the first biochemical evidence that nuclear
      background plays a critical role in the phenotypic manifestation of non-syndromic
      hearing loss and aminoglycoside toxicity associated with the C1494T mutation.

PMID- 15722489
TI  - Intimate partner violence research in the health care setting: what are
      appropriate and feasible methodological standards?
AB  - The past 20 years of research has exposed the profound cost of intimate partner
      violence (IPV) in health care problems and health care dollars for victims and
      bystanders. As a result, professional organizations encourage clinicians to
      identify IPV victims and to refer them to community resources. To date there is
      little evidence to show the value of these efforts, and many completed studies
      are criticized for methodological weaknesses. IPV studies are challenging to
      design, and the double-blind randomized controlled trial may be an impossible
      standard. To move forward, funders and study committees are encouraged to
      reassess the standards for IPV research methodologies.

PMID- 15722490
TI  - Post-traumatic stress disorder (PTSD): what we have learned and what we still
      have not found out.
AB  - This article discusses the biomedical and the social constructionist models
      applied to response to trauma, presents the prevalence and the etiology of post
      traumatic stress disorder (PTSD), and describes its biological and psychological
      correlates in children and adults. It concludes that future research might
      benefit from investigating factors that may protect people who have been exposed
      to an event likely to be traumatic from presenting with PTSD symptoms, and
      factors that may affect the longitudinal course of PTSD and treatment
      effectiveness.

PMID- 15722492
TI  - Improving violence intervention outcomes by integrating alcohol treatment.
AB  - There is extensive empirical and theoretical support for a link between alcohol
      use and intimate partner violence. Recent innovations in the assessment of these
      constructs have shown a strong temporal link between alcohol use and intimate
      partner violence. The majority of men participating in batterer intervention
      programs have alcohol problems, and these men are at very high risk for violence
      recidivism. Research has shown substantial decreases in partner violence among
      alcoholics subsequent to obtaining alcohol treatment. It is likely that violence
      outcomes could be significantly improved by incorporating alcohol treatment as a
      standard component of batterer intervention programs.

PMID- 15722491
TI  - Combating child homicide: preventive policing for the new millennium.
AB  - High-profile media coverage of crimes against children has heightened public
      awareness of critical child safety needs and issues. However, numerous research
      studies in the area of child homicide have illustrated the importance of the
      power of science to correct false perceptions and misinformation, improving how
      to best serve and protect our children. Age-based analyses of childhood crime
      patterns have vastly improved how law enforcement and social service
      practitioners identify, investigate, and resolve child victimization cases.
      Future protective efforts must involve multiagency and multidisciplinary
      collaboration. Law enforcement, social service clinicians, educators, and
      academicians should jointly develop and implement pragmatic and effective
      prevention, detection, and resolution programs and policies.

PMID- 15722493
TI  - Intimate partner violence and post-traumatic stress disorder symptoms in women:
      what we know and need to know.
AB  - This article presents a review of knowledge regarding post-traumatic stress
      disorder (PTSD) in women experiencing intimate partner violence. Knowledge
      related to the prevalence and predictors of PTSD in battered women, the
      association between PTSD and physical health, and the emerging science regarding
      PTSD and physiological and immune parameters is addressed. Primary
      recommendations for future research includes the need for longitudinal and
      intervention research that incorporates a range of psychosocial and physiologic
      health outcomes.

PMID- 15722494
TI  - Beyond PTSD: an evolving relationship between trauma theory and family violence
      research.
AB  - During the past 20 years, we have learned how similarly harmful are experiences
      of terror, violence, and abuse, whether they occur on the combat field or at
      home. The field of family violence has gained much from the field of traumatic
      stress, and collaborations between these two previously separate fields have
      yielded important new answers, as well as new research questions. The field of
      traumatic stress is poised to integrate, more fully than in the past, a variety
      of aspects of trauma such as social betrayal, as well as outcomes of trauma such
      as depression, criminality, and physiological harm that go beyond posttraumatic
      stress. The field of family violence has much to offer in this process. We look
      forward to improved research designs that will further our knowledge of how
      trauma affects aspects of people's lives, including productivity, relationships,
      cognition, and emotions, in negative and positive ways.

PMID- 15722495
TI  - Trauma and violence research: taking stock in the 21st century.
AB  - Thirty years after the first national estimates of intimate partner violence were
      published, the field has reached such a level of maturity that complex questions
      can be posed and sophisticated research studies can be designed to answer them.
      Out of this body of research, one of the most important things that researchers
      have learned is that violence and trauma are experienced in different ways by
      different individuals and as a result, require different types of prevention and
      intervention approaches. With this greater understanding of the problems of
      violence and trauma, together with a commitment to inclusive and practical
      research, the field is poised to move forward toward the ultimate goal of
      violence prevention.

PMID- 15722496
TI  - Advances and future directions in the study of children's neurobiological
      responses to trauma and violence exposure.
AB  - One of the most exciting developments to emerge from the field in the past 20
      years is the increasing attention to neurobiological responses to violence and
      trauma exposure. Although researchers have yet to identify a consensual pattern
      of neurobiological response to violence and trauma exposure, it does appear that
      some type of alteration in the hypothalamic pituitary adrenal (HPA) axis is
      likely. This article briefly reviews the multiple moderating factors that help
      account for the divergent patterns in HPA function as well as methodological
      advances that will continue to improve the assessment of HPA function in youth
      exposed to violence and trauma.

PMID- 15722497
TI  - Contributions to the study of violence and trauma: multisystemic therapy,
      exposure therapy, attachment styles, and therapy process research.
AB  - The prevention of future violence through engaging violent adolescents in
      multisystemic therapy and the treatment of trauma with exposure therapy are two
      of the most important scientific advances in the field of interpersonal violence
      in the past 20 years. A particularly significant methodological innovation is the
      development of reliable and valid measures of childhood and adult attachment
      because attachment deficits and their remediation are central to understanding
      and treating perpetrators of violence. In the coming decades, we need to refine
      existing treatment programs to make them effective for cases currently classified
      as treatment resistant. This will involve psychotherapy process research on the
      interaction between therapeutic mechanisms of change and unique personal
      vulnerabilities of treatment-resistant cases.

PMID- 15722498
TI  - Twenty years of progress in addressing domestic violence: an agenda for the next
      10.
AB  - The past 20 years have seen great strides in addressing violence against women by
      their male partners. Although the author cannot point to one single intervention
      or set of interventions as being the most effective, institutional reforms that
      have included coordinated community responses have had a positive impact. During
      the next 10 years, researchers must learn how to address the obstacles that
      prevent institutional responses from being more effective in addressing the needs
      of victims.

PMID- 15722499
TI  - Youth violence in everyday life.
AB  - What we now know about violence in the United States is that it is a common
      occurrence and recurrence for youth. Self-report methods have greatly enhanced
      our understanding of interpersonal violence. Specifically, from the 1980s to the
      present the age group most vulnerable to violence is youth. In addition, and in
      any given year, one third will physically fight with peers, more than one third
      physically fight with dating partners, and a majority of those who fight with
      either peers or partners will repeat this at least one more time.

PMID- 15722500
TI  - Domestic violence research: what have we learned and where do we go from here?
AB  - Domestic violence has been an intense area of study in recent decades. Early
      studies helped with the understanding of the nature of perpetration, the cycle of
      violence, and the effect of family violence on children. More recently, studies
      have focused on beginning to evaluate domestic violence interventions and their
      effects on recidivism. This article acknowledges the importance of what we have
      learned about the prevalence and impact of domestic violence and explores the
      need for more focused effort to pinpoint interventions that are effective with
      perpetrators and victims. Methodological issues relevant to past intervention
      studies are also discussed and future research directions are outlined.

PMID- 15722501
TI  - Does childhood sexual abuse set in motion a cycle of violence against women?:
      what we know and what we need to learn.
AB  - This article reviews evidence for the deleterious effects of childhood sexual
      abuse on female development in both the acute and long-term phases. Taken in
      aggregate, there is evidence to suggest a persistent cycle of violence
      perpetrated against women that begins in childhood in the form of sexual abuse,
      reemerges later in adolescence and early adulthood in the form of physical
      assault or sexual revictimization, and ultimately places the next generation at
      considerable risk for victimization. The differential effect of the
      characteristics of sexual abuse and the wide variation in the onset and
      developmental course of symptoms are underscored. The need for adequate models
      elucidating mechanisms behind this continued cycle of violence is discussed.

PMID- 15722502
TI  - Intimate partner violence in the U.S. general population: progress and future
      directions.
AB  - This article reviews survey research on intimate partner violence (IPV) in the
      U.S. general population. Results from survey research conducted over the past
      quarter century are briefly summarized. Three additional national studies related
      to injuries, crime victimization, and homicide among intimate partners in the
      United States are also considered. The article emphasizes the progress that has
      been made in general population survey research related to IPV. It concludes with
      a discussion of the current controversies and future directions for survey
      research of IPV in the U.S. general population.

PMID- 15722503
TI  - Violence and trauma: the past 20 and next 10 years.
AB  - The issues of violence and trauma over the past 20 years have generated a
      significant amount of research. However, the development of each field has
      remained, for the most part, exclusive from the other. Therefore, the goal of
      this article is to address this shortcoming within the literature by responding
      to three important questions: (a) What is the most important thing we have
      learned about violence and trauma in the past 20 years? (b) What is the most
      important thing we need to learn in the next 10 years? and (c) What is the most
      promising methodological innovation in the past 20 years for the study or
      treatment of trauma or interpersonal violence? This article concludes that by
      increasing the discourse between the two fields, both research fields may be
      better able to develop conceptually, methodologically, and empirically.

PMID- 15722504
TI  - Refocusing on women: a new direction for policy and research on intimate partner
      violence.
AB  - A key question facing researchers of intimate partner violence is how the real
      life contexts of victims' lives should affect state policy. The bulk of recently
      adopted and much touted criminal justice reforms have taken the form of
      relatively inflexible, one-size-fits-all mandatory responses focused on
      counseling, restraining, and punishing batterers. Even the protection order
      system relies far more heavily on batterer treatment programs than on victim
      support to prevent future violence. Together, these reforms have largely
      sacrificed the contextualized, woman-centered focus from which the antidomestic
      violence movement originated. Recently, however, a small body of research has
      emerged indicating that responding flexibly to victims' needs and providing them
      with advocacy and broad social support could be a more successful strategy for
      keeping women safe. These data highlight the importance of expanding victim
      centered resources and reincorporating a particularized perspective into current
      policy and practice. Development of this literature should guide future reform
      efforts.

PMID- 15722505
TI  - Twenty years of progress in the study of trauma.
AB  - In this article, the authors argue that studies investigating the nature of
      traumatic memory have made the greatest contribution to trauma research in the
      past 20 years. Neuroimaging studies provide empirical support for the diagnosis
      of posttraumatic stress disorder and have important implications for the
      treatment of trauma survivors. In the future, the authors hope to see an
      empirically derived model of trauma that incorporates both mediating and
      moderating factors to predict outcome.

PMID- 15722506
TI  - The discovery of acquaintance rape: the salience of methodological innovation and
      rigor.
AB  - Over the past 20 years, research has uncovered the many types of sexual
      victimizations women experience. Findings regarding the victim-offender
      relationship in such incidents have undoubtedly been among the most striking.
      Particularly salient is the revelation that the sexual abuse of and violence
      against women-including rape-most often are perpetrated not by a stranger but by
      someone known to the victim. Without the innovation and implementation of
      victimization surveys with behaviorally specific questions, this knowledge may
      have remained unknown. Instead, armed with such knowledge, prevention and
      education efforts can be fashioned to address sexual victimizations committed by
      someone known to the victim. In this article, we address these issues related to
      key developments in sexual victimization research.

PMID- 15722507
TI  - Measuring intimate partner violence (IPV): you may only get what you ask for.
AB  - With the goal of understanding the true extent of intimate partner violence
      (IPV), researchers have put tremendous effort over the past 20 years developing,
      revising, and assessing IPV screening instruments. The enhancements made in IPV
      instrumentation reflect our improved understanding of the nature of IPV.
      Unfortunately, as is often the case with progress, we are presently at the stage
      where IPV researchers have an arsenal of multiple IPV screens that are, in some
      cases, slightly different, whereas in others, the differences are sizeable. This
      article explores the evolution and variation of a sample of IPV screens. To
      further progress in IPV research, we must make conscious decisions concerning the
      best tool for our individual research. Simultaneously, we must enhance our
      understanding of how these IPV screening instruments overlap so that comparisons
      of IPV prevalence or incidence across time and population are possible.

PMID- 15722508
TI  - Nature-nurture interplay: genetically informative designs contribute to
      understanding the effects of trauma and interpersonal violence.
AB  - The past two decades have seen an explosion in research in the fields of violence
      and trauma and behavior genetics. These two fields came into direct conflict when
      Lisabeth Fisher DiLalla and Irving I. Gottesman outlined a fundamental conceptual
      limitation of trauma and violence research: that rather than being causal, the
      well-documented relationship between exposure to trauma or violence and later
      negative outcomes could be explained by gene-environment correlation. In the past
      decade, researchers have addressed this limitation by studying the effects of
      trauma and violence using genetically informative designs. This report briefly
      discusses the gains made from this research approach and the promising future for
      genetically informative trauma and violence research.

PMID- 15722509
TI  - Culture and interpersonal violence research: paradigm shift to create a full
      continuum of domestic violence services.
AB  - This article addresses the importance of culture within the context of domestic
      violence. It takes the position that to work more effectively with diverse
      cultural groups, the development of a full continuum of services that includes
      eliminating the violence and keeping families together is required. The authors
      believe that intervention models developed in the fields of HIV/AIDS may provide
      important examples for future work.

PMID- 15722510
TI  - Vascular endothelial growth factor receptor 2 blockade disrupts postnatal lung
      development.
AB  - Vascular endothelial growth factor (VEGF) is necessary for normal postnatal lung
      development and may underlie the structural lung damage that follows hyperoxic
      exposure. To determine the individual roles of VEGF receptors (VEGFR) 2 and 1 on
      postnatal lung growth, neonatal mice were treated with neutralizing antibodies to
      VEGFR-2 (DC101) or VEGFR-1 (MF1) in the perinatal period. At 1 wk of age, mice
      treated with DC101 on Days 2 and 4 of life had significantly larger mean alveolar
      diameters consistent with impaired alveolization. By 2 wk of age, however,
      perinatally treated DC101 mice had normal-appearing alveolar structure. Mice
      exposed to perinatal hyperoxia (O(2)) also had larger mean alveolar diameters at
      1 wk of age, but unlike DC101-treated mice, their mitotic index was decreased at
      1 wk of age and they had persistent alveolar enlargement beyond the first 2 wk of
      life. The O(2)-treated lung also had an increase in caspase 3 at 1 wk of age and
      significantly greater expression of nitrotyrosine at 2 wk of age. Therefore,
      VEGFR-2 blockade in the perinatal period disrupts early alveolar development, but
      the effect is reversible with time, whereas hyperoxic lung injury is associated
      with ongoing lung structural impairment.

PMID- 15722511
TI  - Herpes simplex virus type 2 membrane protein UL56 associates with the kinesin
      motor protein KIF1A.
AB  - The herpes simplex virus UL56 gene product is a C-terminal-anchored, type II
      membrane protein of unknown function. UL56 was found to interact with KIF1A, a
      member of the kinesin-3 family, in a yeast two-hybrid screen and a GST pull-down
      assay. KIF1A mediates the transport of synaptic vesicle precursors and is
      essential for the function and viability of neurons. When overexpressed, KIF1A co
      localized with full-sized UL56, but no clear co-localization was observed when co
      expressed with the UL56 mutant protein lacking its C-terminal transmembrane
      domain (TMD). Although the C-terminal TMD was not essential for the interaction
      with KIF1A in the yeast two-hybrid screen and GST pull-down assays, these results
      indicate that the C-terminal TMD, as well as aa 69-217, of UL56 are important for
      the interaction with KIF1A in vivo. The hypothesis that the UL56 protein affects
      vesicular trafficking in infected cells, potentially by acting as a receptor for
      motor proteins in neurons, is discussed.

PMID- 15722512
TI  - Ets-2 repressor factor recruits histone deacetylase to silence human
      cytomegalovirus immediate-early gene expression in non-permissive cells.
AB  - Previous work from this laboratory has shown that expression of human
      cytomegalovirus (HCMV) immediate-early (IE) genes from the major immediate-early
      promoter (MIEP) is likely to be regulated by chromatin remodelling around the
      promoter affecting the acetylation state of core histone tails. The HCMV MIEP
      contains sequences that bind cellular transcription factors responsible for its
      negative regulation in undifferentiated, non-permissive cells. Ets-2 repressor
      factor (ERF) is one such factor that binds to such sequences and represses IE
      gene expression. Although it is not known how cellular transcription factors such
      as ERF mediate transcriptional repression of the MIEP, it is likely to involve
      differentiation-specific co-factors. In this study, the mechanism by which ERF
      represses HCMV IE gene expression was analysed. ERF physically interacts with the
      histone deacetylase, HDAC1, both in vitro and in vivo and this physical
      interaction between ERF and HDAC1 mediates repression of the MIEP. This suggests
      that silencing of viral IE gene expression, associated with histone deacetylation
      events around the MIEP, is mediated by differentiation-dependent cellular factors
      such as ERF, which specifically recruit chromatin remodellers to the MIEP in non
      permissive cells.

PMID- 15722513
TI  - Rhesus brain microvascular endothelial cells are permissive for rhesus
      cytomegalovirus infection.
AB  - Endothelial cells (EC) are an important cell type for human cytomegalovirus (CMV)
      pathogenesis. To characterize better the role of EC in primate CMV natural
      history, rhesus macaque microvascular EC (MVEC) were purified from fetal brain
      and analysed for infectivity by rhesus cytomegalovirus (RhCMV). Rhesus brain MVEC
      (BrMVEC) in culture were positive for von Willebrand factor and CD105 expression,
      uptake of acetylated low-density lipoprotein, and formation of capillary-like
      tubules on Matrigel, all phenotypic hallmarks of EC. BrMVEC were fully permissive
      for infection by RhCMV strain 68-1, and detectable plaques formed within 5 days
      of infection. Infectivity of BrMVEC by RhCMV could be reduced, but not abolished,
      by treatment of cells either before or during infection with pro-inflammatory
      mediators tumour necrosis factor-alpha, interleukin-1beta or phorbol 12-myristate
      13-acetate. These results demonstrate that in vitro infection of rhesus BrMVEC is
      a dynamic process that is influenced by activation conditions.

PMID- 15722514
TI  - Epstein-Barr virus latent membrane protein 2A mimics B-cell receptor-dependent
      virus reactivation.
AB  - Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) shares protein
      motifs with the B-cell receptor that play a role in B-cell receptor signalling
      and has been shown to mimic an activated B-cell receptor by providing a survival
      signal for mature B cells in transgenic mice. Conversely, LMP2A has been reported
      not to support but to inhibit B-cell receptor signalling with respect to virus
      reactivation and to block lytic virus induction after anti-Ig treatment of EBV
      infected B cells. To solve this apparent paradox, the role of LMP2A in lytic
      cycle induction was re-examined in B cells conditionally immortalized by EBV. It
      was shown that, in the absence of other stimuli, LMP2A expression alone could
      lead to induction of the virus lytic cycle. Similarly to B-cell receptor
      stimulation by anti-Ig treatment, this LMP2A-mediated reactivation was dependent
      on the mitogen-activated protein kinase pathway and could be inhibited by the
      viral LMP1. Our data reinforce the notion that LMP2A is a functional homologue of
      the B-cell receptor, not only with respect to B-cell survival but also with
      respect to regulation of the lytic cycle.

PMID- 15722515
TI  - Transcription of the murine gammaherpesvirus 68 ORF73 from promoters in the viral
      terminal repeats.
AB  - Gammaherpesviruses persist as latent episomes in a dynamic lymphocyte pool. The
      regulated production of an episome maintenance protein is therefore crucial to
      their survival. The transcription initiation site of the murine gammaherpesvirus
      68 episome maintenance protein, ORF73, was mapped to the viral terminal repeats,
      more than 10 kb distant from the open reading frame (ORF) itself. A 5' non-coding
      exon in the terminal repeats was spliced to the right end of the viral unique
      sequence, and then across ORFs 75a, 75b, 75c and 74 to ORF73. The right-hand
      portion of a single repeat unit was sufficient for constitutive promoter
      activity. The unique left end of the viral genome further enhanced ORF73
      transcription. This, together with the large size of the predominant ORF73 mRNA,
      suggested that transcription initiates in distal repeat units and then splices
      between repeats to generate an extensive 5' untranslated region. A second
      promoter in the left-hand portion of the proximal terminal repeat unit generated
      a transcript which overlapped that of ORF73, but failed to splice to the ORF73
      coding exon and so transcribed ORF75a. In distal repeat copies, however,
      transcription from this promoter would enter the next repeat unit to become an
      ORF73 mRNA. There was a third promoter just upstream of ORF73 itself. These data
      indicate that ORF73 transcription is highly complex, and support the idea that
      the terminal repeats of gamma-2-herpesviruses constitute a vital component of
      episomal persistence.

PMID- 15722516
TI  - Experimental infection of sheep with ovine herpesvirus 2 via aerosolization of
      nasal secretions.
AB  - Ovine herpesvirus 2 (OvHV-2) is the causative agent of sheep-associated malignant
      catarrhal fever in clinically susceptible ruminants, including cattle, bison and
      deer. Studies of OvHV-2 have been hampered by the lack of an in vitro propagation
      system. Here, the use of nasal secretions collected from OvHV-2-infected sheep
      experiencing intense virus shedding episodes as a source of infectious virus for
      experimental animal infections was examined. OvHV-2 uninfected sheep were
      nebulized with nasal secretions containing approximately 10(8) to 10(1) copies of
      OvHV-2 DNA. The time to detectable viral DNA in peripheral blood leukocytes (7-12
      days post-infection) and virus-specific antibody in plasma (9-32 days post
      infection) varied with the dose of inocula administered. Here, the use of nasal
      secretions as a source of infectious OvHV-2 was defined and the minimum
      infectious dose of a pool of nasal secretions that can be used in further studies
      of viral pathogenesis and vaccine development was determined.

PMID- 15722517
TI  - The herpesvirus saimiri Rta gene autostimulates via binding to a non-consensus
      response element.
AB  - Herpesvirus saimiri ORF 50a protein expression is sufficient to reactivate the
      entire lytic-replication cycle. ORF 50a functions as a sequence-specific
      transactivator that is capable of activating delayed-early gene expression via
      direct binding to an ORF 50 response element (RE) within the respective promoter.
      Here, it is shown that ORF 50a is capable of transactivating its own promoter.
      Deletion analysis of the ORF 50a promoter showed that the ORF 50-responsive
      element is contained within an 80 bp fragment, situated 293-373 bp from the
      transcription initiation site. Gel-retardation analysis further mapped the RE to
      a 34 bp fragment that was able to confer ORF 50 responsiveness to an enhancerless
      SV40 minimal promoter. Sequence analysis showed that this RE has no direct
      similarity to previously identified ORF 50 REs. Therefore, it is concluded that
      ORF 50a is capable of stimulating its own promoter via a novel RE.

PMID- 15722518
TI  - African swine fever virus infection disrupts centrosome assembly and function.
AB  - African swine fever virus (ASFV) is a large, enveloped DNA virus that assembles
      in perinuclear sites located close to the centrosome. It is reported here that
      the microtubule network becomes disorganized soon after the onset of viral DNA
      replication and formation of assembly sites. ASFV infection resulted in loss of
      gamma-tubulin and pericentrin at the centrosome; this was due to protein
      relocalization, but not degradation. ASFV infection also inhibited the ability of
      the centrosome to nucleate microtubules. The reorganization of microtubules seen
      in ASFV-infected cells may therefore be mediated by gamma-tubulin and pericentrin
      redistribution, and consequent disruption of centrosome assembly and function.

PMID- 15722519
TI  - Characterization of genotype H hepatitis B virus strain identified for the first
      time from a Japanese blood donor by nucleic acid amplification test.
AB  - The Japanese Red Cross has been conducting a nucleic acid amplification test
      (NAT) screening for hepatitis B virus (HBV), hepatitis C virus and human
      immunodeficiency virus 1 among blood donors since July 1 1999. The first case of
      HBV genotype H was found and reported in Japan. Serological markers of HBV were
      not detected in this NAT-positive donation. It may be that the positive donation
      was in the serological window period at the early stage of infection. The
      complete genome of 3215 nt was sequenced, and the sequence had 99.3 % homology
      with the strain from Los Angeles, USA (LSA2523). Here, a leucine zipper motif was
      found in the region of the HBV surface antigen conserved through genotypes A-H.

PMID- 15722520
TI  - Induction of mucosal and systemic immune response by single-dose oral
      immunization with biodegradable microparticles containing DNA encoding HBsAg.
AB  - The purpose of this work was to assess the ability of plasmid DNA encoding
      hepatitis B virus (HBV) HBsAg encapsulated in poly(DL-lactide-co-glycolic acid)
      (PLGA) microparticles to induce local and systemic HBsAg-specific immunity
      following a single dose of oral immunization. RT-PCR analysis demonstrated
      prolonged transcription of plasmid DNA, consistent with the sustained expression
      and presentation of target antigen observed by confocal laser scanning
      microscopy, in gut-associated lymphocyte tissue (GALT) from mice immunized orally
      with plasmid DNA encapsulated into PLGA microparticles. Oral administration of
      PLGA-DNA microparticles induced a long-lasting and stable antigen-specific
      antibody response, both serum total antibody and intestinal IgA, in BALB/c mice.
      Mice immunized orally exhibited antigen-specific gamma interferon production and
      cytotoxic T lymphocyte responses in spleen and GALT after restimulation in vitro
      with HBsAg or tumour cells stably expressing HBsAg. In contrast, naked DNA
      vaccines given by intramuscular injection induced only systemic cellular and
      humoral responses to HBsAg, which were much lower than the responses elicited by
      oral DNA encapsulated in PLGA microparticles at equivalent doses. The results are
      encouraging with regard to obtaining good compliance and vaccination coverage
      with candidate plasmid DNA vaccines, especially in developing countries.

PMID- 15722521
TI  - Downregulation of Bax mRNA expression and protein stability by the E6 protein of
      human papillomavirus 16.
AB  - Previous studies have shown that human papillomavirus (HPV) 16 E6 inhibits
      apoptosis induced during terminal differentiation of primary human keratinocytes
      (PHKs) triggered by serum and calcium. E6 inhibition of apoptosis was accompanied
      with prolonged expression of Bcl-2 and reduced elevation of Bax levels. In the
      present study, the effect of E6 on Bax mRNA expression and protein stability was
      investigated. These studies indicate that stable E6 expression in differentiating
      keratinocytes reduced the steady-state levels of Bax mRNA and shortened the half
      life of Bax protein. These results were confirmed in transiently transfected 293T
      cells where E6 degraded Bax in a dose-dependent manner. Bax degradation was also
      exhibited in Saos-2 cells that lack p53, indicating its p53 independence. E6 did
      not form complexes with Bax and did not induce Bax degradation in vitro under
      experimental conditions where p53 was degraded. Finally, E6 aa 120-132 were shown
      to be necessary for Bax destabilization and, more importantly, for abrogating the
      ability of Bax to induce cellular apoptosis, highlighting the functional
      consequences of the E6-induced alterations in Bax expression.

PMID- 15722522
TI  - Mutation of chicken anemia virus VP2 differentially affects serine/threonine and
      tyrosine protein phosphatase activities.
AB  - Novel dual-specificity protein phosphatases (DSPs), which catalyse the removal of
      phosphate from both phosphotyrosine and phosphoserine/phosphothreonine
      substrates, have recently been identified in two viruses within the family
      Circoviridae. Viral protein 2 (VP2) of chicken anemia virus (CAV) and ORF2 of TT
      virus have been shown to possess DSP activity in vitro. CAV VP2 is unusual in
      possessing two vicinal cysteines within the protein phosphatase signature motif.
      The first cysteine residue (C95) within the motif has been identified by
      mutagenesis as the essential catalytic cysteine. In this study, it was shown that
      virus mutated at this residue displayed a marked inhibition of growth, with
      titres reduced 10(4)-fold, and reduced cytopathogenic effect in cell culture,
      indicating that viral DSP activity may be significant during infection. As with
      virus mutated at the first cysteine residue, mutation of the second cysteine
      (C97) within the motif resulted in a marked reduction in viral growth and
      attenuation of cytopathogenicity in infected cell cultures. However, mutagenesis
      of this second cysteine only reduced phosphotyrosine phosphatase activity to 70 %
      of that of wild-type VP2, but increased phosphoserine/phosphothreonine
      phosphatase activity by as much as 700 %. The differential effect of the C97S
      mutation on VP2 activity does not appear to have parallels in other DSPs and
      suggests a unique role for the second cysteine in the function of these viral
      proteins, particularly in vivo.

PMID- 15722523
TI  - Pig anelloviruses are highly prevalent in swine herds in France.
AB  - A survey of anelloviruses in swine herds from Britanny, France, is reported. By
      using PCR targeted to the conserved untranslated region, prevalences of 93 and 73
      % were found among 15 herds and 33 animals, respectively. The lung was the organ
      found to be positive most frequently among the five organs tested from 32
      animals. The highest identity levels of our nucleotide sequences were found with
      pig isolates from Japan and with an isolate from Tupaia belangeri. Interestingly,
      when aligning all available swine isolates from France and Japan, at least two
      phylogenetic groups were identified, each one containing clones from France and
      Japan. Some animals carried clones from both groups, demonstrating intra
      individual variability. Despite the putative harmlessness of anelloviruses, the
      potential inoculum carried by pigs must be further evaluated as a sanitary
      threat.

PMID- 15722524
TI  - Formation of Bombyx mori nucleopolyhedrovirus IE2 nuclear foci is regulated by
      the functional domains for oligomerization and ubiquitin ligase activity.
AB  - Baculovirus IE2 functions as a transregulator and is also involved in viral DNA
      replication. However, the mechanism for these functions remains unknown. It has
      previously been reported that Bombyx mori nucleopolyhedrovirus (BmNPV) IE2 has a
      ubiquitin ligase activity that is dependent on the RING finger domain and that
      IE2 can oligomerize through its C-terminal coiled-coil region. Here, confocal
      microscopy analysis demonstrated that IE2 formed nuclear foci only during the
      early phase of infection (2-6 h post-infection). Therefore, it was determined
      whether the IE2 functional regions described above could affect this
      characteristic distribution. Transient expression of ie2 also showed focus
      formation, suggesting that IE2 does not require any other viral factors. IE2
      mutants lacking the C-terminal coiled-coil region did not form foci, while a
      mutant of the RING finger domain showed nuclear foci that appeared larger and
      brighter than those formed by wild-type IE2. In addition, IE2 exhibited enlarged
      foci in infected cells following treatment with a proteasome inhibitor,
      suggesting that foci enlargement resulted from accumulation of IE2 due to
      inhibition of the ubiquitin-proteasome pathway. These results suggest that BmNPV
      IE2 oligomerization and ubiquitin ligase activity functional domains regulate
      nuclear foci formation.

PMID- 15722525
TI  - Genetic variation and dynamics of hepatitis C virus replicons in long-term cell
      culture.
AB  - Hepatitis C virus (HCV) genomic sequences are known to vary widely among HCV
      strains, but to date there have been few reports on the genetic variations and
      dynamics of HCV in an experimental system of HCV replication. In this study, a
      genetic analysis of HCV replicons obtained in long-term culture of two HCV
      replicon cells (50-1 and 1B-2R1), which were established from two HCV strains, 1B
      1 and 1B-2, respectively, was performed. One person cultured 50-1 cells for 18
      months, and two people independently cultured 50-1 cells for 12 months. 1B-2R1
      cells were also cultured for 12 months. The whole nucleotide sequences of the
      three independent replicon RNA clones obtained at several time points were
      determined. It was observed that genetic mutations in both replicons accumulated
      in a time-dependent manner, and that the mutation rates of both replicons were
      approximately 3.0 x 10(-3) base substitutions/site/year. The genetic diversity of
      both replicons was also enlarged in a time-dependent manner. The colony formation
      assay by transfection of total RNAs isolated from both replicon cells at
      different time points into naive HuH-7 cells revealed that the genetic mutations
      accumulating with time in both replicons apparently improved colony formation
      efficiency. Taken together, these results suggest that the HCV replicon system is
      useful for the analysis of evolutionary dynamics and variations of HCV. Using
      this replicon cell culture system, it was demonstrated further that neither
      ribavirin nor its derivative mizoribine accelerated the mutation rate or the
      increase in the genetic diversity of HCV replicon.

PMID- 15722526
TI  - Mitogen-induced upregulation of hepatitis C virus expression in human lymphoid
      cells.
AB  - Considering growing evidence indicating that hepatitis C virus (HCV) replicates
      in lymphoid cells, establishment of a reliable and sensitive method for detection
      of HCV in these cells may provide means for monitoring the infection and the
      efficacy of sterilizing antiviral therapy. In this study, conditions for ex vivo
      augmentation and detection of the HCV genome in peripheral blood mononuclear
      cells (PBMCs) from patients with chronic hepatitis C (CHC) or after a sustained
      virological response (SVR) to antiviral treatment were assessed. Following
      stimulation with combinations of mitogens and/or cytokines, PBMCs and, in certain
      cases, affinity-purified T and B cells were examined for HCV positive- and
      negative-strand RNA by using RT-PCR followed by nucleic acid hybridization, while
      the presence of viral NS3 protein was determined by flow cytometry. HCV RNA
      augmentation was assessed by quantification of Southern and dot-blot
      hybridization signals. The results showed that treatment of peripheral lymphoid
      cells with mitogens stimulating T- and B-cell proliferation and with cytokines
      supporting their growth significantly increased HCV RNA detection in patients
      with both CHC and SVR. This enhancement was up to 100-fold for the HCV genome and
      fivefold for the NS3 protein compared with untreated cells. In conclusion, HCV
      RNA can be readily detected in circulating lymphoid cells in progressing
      hepatitis C and following SVR after ex vivo cell stimulation. As such, this
      method offers a new investigative tool to study HCV lymphotropism and to monitor
      virus presence during the course of HCV infection.

PMID- 15722527
TI  - Analysis of the processing and transmembrane topology of the E2p7 protein of
      hepatitis C virus.
AB  - Hepatitis C virus C, E1, E2 and p7 proteins are cleaved from a viral polyprotein
      by host signal peptidases. Cleavage at the E2/p7 site is incomplete in genotype
      1a strain H (resulting in E2, p7 and E2p7 species), although it has been reported
      to be more efficient in genotype 1b strain BK. Here, the proteolytic processing
      and transmembrane topology of genotype 1a strain H77c p7 was investigated when
      expressed in the context of E2p7. Partial processing was seen at the E2/p7 site
      in mammalian cells, the efficiency of which improved in the presence of
      nucleotide sequences downstream of p7. In insect cells, no processing at the
      E2/p7 site occurred and the uncleaved E2p7 species was incorporated into virus
      like particles when expressed in the context of CE1E2p7c-myc. E2p7c-myc formed a
      heterodimer with E1, indicating that, like the well-characterized E1-E2 complex,
      the E1-E2p7 heterodimer may also play a functional role in virus replication.
      Comparison of the p7 signal peptide sequences of strains BK and H77c revealed 3
      aa differences (positions 720, 733 and 742). Mutational analysis showed that the
      V720L change in the H77c sequence substantially increased processivity at the
      E2/p7 site. The p7 protein adopts a double membrane-spanning topology with both
      its N and C termini orientated luminally in the endoplasmic reticulum. The
      transmembrane topology of E2p7 species was examined by two independent means. In
      both cases, the C terminus of p7 in E2p7 was found to be cytoplasmically
      orientated, indicating that p7 adopts a dual transmembrane topology.

PMID- 15722528
TI  - Hepatitis C virus and hepatitis B virus bind to heparin: purification of largely
      IgG-free virions from infected plasma by heparin chromatography.
AB  - Binding to heparin of hepatitis C virus (HCV) and hepatitis B virus (HBV) from
      chronic carriers was investigated. Eighty per cent of HCV RNA from an
      agammaglobulinaemic patient (IgG-free virus) was retained on immobilized heparin
      and eluted with > or =0.4 M NaCl, in contrast to approximately 20 % from
      immunocompetent chronic carriers (with < or =8 % IgG-free virus). Increased
      binding to heparin of the HCV fraction that was not retained by a protein G
      column suggested that antibodies complexed to the virions partially inhibited the
      interaction. A higher proportion (15-80 %) of HBV from chronic carriers bound to
      heparin and eluted with > or =0.4 M NaCl. After washing of the heparin columns
      with 0.3 M NaCl, <1 % of total plasma proteins co-eluted with HCV or HBV. By this
      one-step heparin chromatography, without ultracentrifugation, IgG-free HCV and
      IgG-free HBV were preferentially purified from human plasma by 1000-fold and
      greater than 500-fold, respectively. Following assessment with an anti-E2
      envelope protein antibody, the amount of immunoprecipitated HCV particles after
      heparin purification was similar to that in the original plasma, suggesting that
      undamaged virions were purified. This was further supported by heparin-purified
      HCV binding to lymphocyte cell lines in a dose-dependent manner. Intact HBV
      particles were detected by electron microscopy. It was concluded that HCV and HBV
      from chronically infected patients bind to heparin, the closest homologue of
      liver heparan sulfate, and that heparin chromatography is an efficient and gentle
      method for purifying these viruses from human plasma. In the absence of cell
      culture systems or alternative robust purification methods, heparin
      chromatography may help greatly in binding and infectivity studies.

PMID- 15722529
TI  - Foot-and-mouth disease virus replication sites form next to the nucleus and close
      to the Golgi apparatus, but exclude marker proteins associated with host membrane
      compartments.
AB  - Picornavirus infection of cells generally results in the production of membranous
      vesicles containing the viral proteins necessary for viral RNA synthesis. To
      determine whether foot-and-mouth disease virus (FMDV) infection induced similar
      structures, and which cellular components were involved, the subcellular
      distribution of FMDV proteins was compared with protein markers of cellular
      membrane compartments. Using immunofluorescence analysis and digital
      deconvolution, it was shown that FMDV structural and non-structural proteins co
      localize to punctate structures in juxtanuclear virus assembly sites close to the
      Golgi complex. Significantly, viral protein 2C did not co-localize with marker
      proteins of the cis- or medial-Golgi compartments or trans-Golgi network.
      Furthermore, incubation of infected cells with brefeldin A caused a
      redistribution of Golgi proteins to the endoplasmic reticulum, but did not affect
      the distribution of 2C and, by inference, the integrity of the virus assembly
      site. Taken with the observation that 2C was membrane-associated, but failed to
      fractionate with Golgi markers on density gradients, it was possible to conclude
      that Golgi membranes were not a source of structures containing 2C. Further
      immunofluorescence analysis showed that 2C was also separate from marker proteins
      of the endoplasmic reticulum, endoplasmic reticulum intermediate compartment,
      endosomes and lysosomes. The results suggest that the membranes generated at FMDV
      assembly sites are able to exclude organelle-specific marker proteins, or that
      FMDV uses an alternative source of membranes as a platform for assembly and
      replication.

PMID- 15722530
TI  - Phylogenetic analysis of human rhinovirus capsid protein VP1 and 2A protease
      coding sequences confirms shared genus-like relationships with human
      enteroviruses.
AB  - Phylogenetic analysis of the capsid protein VP1 coding sequences of all 101 human
      rhinovirus (HRV) prototype strains revealed two major genetic clusters, similar
      to that of the previously reported VP4/VP2 coding sequences, representing the
      established two species, Human rhinovirus A (HRV-A) and Human rhinovirus B (HRV
      B). Pairwise nucleotide identities varied from 61 to 98 % within and from 46 to
      55 % between the two HRV species. Interserotypic sequence identities in both HRV
      species were more variable than those within any Human enterovirus (HEV) species
      in the same family. This means that unequivocal serotype identification by VP1
      sequence analysis used for HEV strains may not always be possible for HRV
      isolates. On the other hand, a comprehensive insight into the relationships
      between VP1 and partial 2A sequences of HRV and HEV revealed a genus-like
      situation. Distribution of pairwise nucleotide identity values between these
      genera varied from 41 to 54 % in the VP1 coding region, similar to those between
      heterologous members of the two HRV species. Alignment of the deduced amino acid
      sequences revealed more fully conserved amino acid residues between HRV-B and
      polioviruses than between the two HRV species. In phylogenetic trees, where all
      HRVs and representatives from all HEV species were included, the two HRV species
      did not cluster together but behaved like members of the same genus as the HEVs.
      In conclusion, from a phylogenetic point of view, there are no good reasons to
      keep these two human picornavirus genera taxonomically separated.

PMID- 15722531
TI  - Intracellular location and translocation of silent and active poliovirus
      replication complexes.
AB  - Replication of poliovirus (PV) genomic RNA in HeLa cells has previously been
      found to start at distinct sites at the nuclear periphery. In the present study,
      the earliest steps in the virus replication cycle, i.e. the appearance and
      intracellular translocation of viral protein and negative-strand RNA prior to
      positive-strand RNA synthesis, were followed. During translation, positive-strand
      RNA and newly synthesized viral protein presented as a dispersed endoplasmic
      reticulum (ER)-like pattern. Concomitant with translation, individual PV vesicle
      clusters emerged at the ER and formed nascent replication complexes, which
      contained newly synthesized negative-strand RNA. The complexes rapidly moved
      centripetally, in a microtubule-dependent way, to the perinuclear area to engage
      in positive-strand viral RNA synthesis. Replication complexes made
      transcriptionally silent with guanidine/HCl followed the anterograde membrane
      pathway to the Golgi complex within the microtubule-organizing centre (MTOC),
      whereas replication complexes active in positive-strand RNA synthesis were
      retained at the nuclear periphery. If the silent replication complexes that had
      accumulated at the MTOC were released from the guanidine block, transcription was
      not readily resumed. Rather, positive-strand RNA was redistributed back to the ER
      to start, after a lag phase, translation, followed by negative- and positive
      strand RNA synthesis in replication complexes migrating to the nuclear periphery.
      As some of the findings appear to be in contrast to events reported in cell-free
      guanidine-synchronized translation/transcription systems, implications for the
      comparison of in vitro systems with the living cell are discussed.

PMID- 15722532
TI  - Isolation of avian infectious bronchitis coronavirus from domestic peafowl (Pavo
      cristatus) and teal (Anas).
AB  - Coronavirus-like viruses, designated peafowl/China/LKQ3/2003 (pf/CH/LKQ3/03) and
      teal/China/LDT3/2003 (tl/CH/LDT3/03), were isolated from a peafowl and a teal
      during virological surveillance in Guangdong province, China. Partial genomic
      sequence analysis showed that these isolates had the S-3-M-5-N gene order that is
      typical of avian coronaviruses. The spike, membrane and nucleocapsid protein
      genes of pf/CH/LKQ3/03 had >99 % identity to those of the avian infectious
      bronchitis coronavirus H120 vaccine strain (Massachusetts serotype) and other
      Massachusetts serotype isolates. Furthermore, when pf/CH/LKQ3/03 was inoculated
      experimentally into chickens (specific-pathogen-free), no disease signs were
      apparent. tl/CH/LDT3/03 had a spike protein gene with 95 % identity to that of a
      Chinese infectious bronchitis virus (IBV) isolate, although more extensive
      sequencing revealed the possibility that this strain may have undergone
      recombination. When inoculated into chickens, tl/CH/LDT3/03 resulted in the death
      of birds from nephritis. Taken together, this information suggests that
      pf/CH/LKQ3/03 might be a revertant, attenuated vaccine IBV strain, whereas
      tl/CH/LDT3/03 is a nephropathogenic field IBV strain, generated through
      recombination. The replication and non-pathogenic nature of IBV in domestic
      peafowl and teal under field conditions raises questions as to the role of these
      hosts as carriers of IBV and the potential that they may have to transmit virus
      to susceptible chicken populations.

PMID- 15722534
TI  - Contamination of a specific-pathogen-free rat breeding colony with Human
      parainfluenzavirus type 3.
AB  - Routine antibody surveillance for Sendai virus in a breeding colony suggested
      viral invasion into laboratory rats. A more specific haemagglutination-inhibition
      test implied that the agent was related closely to Human parainfluenza virus type
      3 (hPIV3), rather than Sendai virus. To isolate this virus, Vero cells were
      inoculated with lung homogenates of 30 young animals from the colony. One of the
      cultures became positive at the second passage by RT-PCR directed to the hPIV3 NP
      and L genes. Cytopathic effect with cell fusion was observed at the third
      passage. The HN gene of this virus (KK24) had >93 % similarity to those of other
      hPIV3 isolates, suggesting a human origin of KK24. Experimental intranasal
      inoculation of KK24 into SD rats showed virus replication in the lungs at 3-5
      days post-infection (p.i.). Pathological examination of the lungs at day 5 p.i.
      indicated a moderate detachment, degradation and apoptosis of bronchial
      epitheliocytes with peribronchial mononuclear infiltrations. At day 7 p.i., these
      changes became less prominent, and no lesions were apparent at day 10 p.i. or
      later. The infected rats seroconverted at day 7 p.i. On the contrary, none of the
      30 experimentally infected ICR mice showed any pathological lesions in their
      lungs, despite seroconversion at 7 days p.i. These results suggest that hPIV3 can
      invade rat colonies and has a moderate and transient pathogenicity in rats. This
      is the first report of non-experimental hPIV3 infection in laboratory rats,
      unexpectedly detected by antibody screening for Sendai virus.

PMID- 15722533
TI  - Intersegmental recombination between the haemagglutinin and matrix genes was
      responsible for the emergence of a highly pathogenic H7N3 avian influenza virus
      in British Columbia.
AB  - In February 2004 a highly pathogenic avian influenza (HPAI) outbreak erupted in
      British Columbia. Investigations indicated that the responsible HPAI H7N3 virus
      emerged suddenly from a low pathogenic precursor. Analysis of the haemagglutinin
      (HA) genes of the low and high pathogenic viruses isolated from the index farm
      revealed the only difference to be a 21 nt insert at the HA cleavage site of the
      highly pathogenic avian influenza virus. It was deduced that this insert most
      probably arose as a result of non-homologous recombination between the HA and
      matrix genes of the same virus. Over the course of the outbreak, a total of 37
      isolates with, and 3 isolates without inserts were characterized. The events
      described here appear very similar to those which occurred in Chile in 2002 where
      the virulence shift of another H7N3 virus was attributed to non-homologous
      recombination between the HA and nucleoprotein genes.

PMID- 15722535
TI  - VaZyMolO: a tool to define and classify modularity in viral proteins.
AB  - Viral structural genomic projects aim at unveiling the function of unknown viral
      proteins by employing high-throughput approaches to determine their 3D structure
      and to identify their function through fold-homology studies. The 'viral enzyme
      module localization' (VaZyMolO) tool has been developed, which aims at defining
      viral protein modules that might be expressed in a soluble and functionally
      active form, thereby identifying candidates for crystallization studies. VaZyMolO
      includes 114 complete viral genome sequences of both negative- and positive
      sense, single-stranded RNA viruses available from NCBI. In VaZyMolO, a module is
      defined as a structural and/or functional unit. Modules were first identified by
      homology search and then validated by the convergence of results from sequence
      composition analysis, motif search, transmembrane region search and domain
      definitions, as found in the literature. The public interface of VaZyMolO, which
      is accessible from http://www.vazymolo.org, allows comparison of a query sequence
      to all VaZyMolO modules of known function.

PMID- 15722536
TI  - Regulation of human immunodeficiency virus 1 transcription by nef microRNA.
AB  - MicroRNAs (miRNAs) are approximately 21-25 nt long and interact with mRNAs to
      lead to either translational repression or RNA cleavage through RNA interference.
      A previous study showed that human immunodeficiency virus 1 (HIV-1) nef dsRNA
      from AIDS patients who are long-term non-progressors inhibited HIV-1
      transcription. In the study reported here, nef-derived miRNAs in HIV-1-infected
      and nef transduced cells were identified, and showed that HIV-1 transcription was
      suppressed by nef-expressing miRNA, miR-N367, in human T cells. The miR-N367
      could reduce HIV-1 LTR promoter activity through the negative responsive element
      of the U3 region in the 5'-LTR. Therefore, nef miRNA produced in HIV-1-infected
      cells may downregulate HIV-1 transcription through both a post-transcriptional
      pathway and a transcriptional neo-pathway.

PMID- 15722537
TI  - Expressing engineered thymidylate kinase variants in human cells to improve AZT
      phosphorylation and human immunodeficiency virus inhibition.
AB  - The triphosphorylated form of the nucleoside analogue AZT (AZTTP) acts as a chain
      terminator during reverse transcription of the human immunodeficiency virus (HIV)
      genome. The bottleneck in the conversion of AZT to AZTTP is the phosphorylation
      of AZT monophosphate (AZTMP) by cellular thymidylate kinase. Human thymidylate
      kinase was engineered to exhibit highly improved activity for AZTMP to AZTDP
      conversion. It was demonstrated here that genetically modified human cells
      transiently expressing these enzyme variants show more than 10-fold higher
      intracellular concentrations of AZTDP and AZTTP. Stable clones expressing these
      enzymes appear to phosphorylate AZTMP less efficiently, but first experiments
      indicate they are still more potent in HIV inhibition than the parental cells. It
      was proposed that the concept of introducing into human cells a catalytically
      improved human enzyme, rather than an enzyme of viral, bacterial or yeast origin,
      may serve as a paradigm for ameliorating the metabolic activation of an
      established drug.

PMID- 15722538
TI  - Nef expressed from human immunodeficiency virus type 1 extrachromosomal DNA
      downregulates CD4 on primary CD4+ T lymphocytes: implications for integrase
      inhibitors.
AB  - Recently developed integrase inhibitors targeting the HIV-1 integrase (IN)
      protein block integration of HIV DNA in the target cell, preventing subsequent
      virus replication. In the absence of integration, viral DNA is shunted towards
      the formation of extrachromosomal DNA (E-DNA). Although HIV-1 E-DNA does not
      support productive replication, it is transcriptionally active and produces viral
      proteins. However, the significance of E-DNA in virus replication and
      pathogenesis is poorly understood. In this study, the functional activity of the
      HIV-1 Nef protein expressed in the absence of viral integration was analysed.
      Using both a recombinant HIV-1 IN defective virus and a diketo acid IN inhibitor,
      evidence was provided showing that Nef expressed from E-DNA downregulates CD4
      surface expression on primary CD4(+) T lymphocytes. These results suggest that
      proteins expressed in the absence of integration may have potential clinical
      consequences, an issue that should be further explored with the introduction of
      IN inhibitors.

PMID- 15722539
TI  - Differences in viral and host genetic risk factors for development of human T
      cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic
      paraparesis between Iranian and Japanese HTLV-1-infected individuals.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) is a neurological disease observed only in 1-2 % of
      infected individuals. HTLV-1 provirus load, certain HLA alleles and HTLV-1 tax
      subgroups are reported to be associated with different levels of risk for HAM/TSP
      in Kagoshima, Japan. Here, it was determined whether these risk factors were also
      valid for HTLV-1-infected individuals in Mashhad in northeastern Iran, another
      region of endemic HTLV-1 infection. In Iranian HTLV-1-infected individuals
      (n=132, 58 HAM/TSP patients and 74 seropositive asymptomatic carriers), although
      HLA-DRB1*0101 was associated with disease susceptibility in the absence of HLA
      A*02 (P=0.038; odds ratio=2.71) as observed in Kagoshima, HLA-A*02 and HLA-Cw*08
      had no effect on either the risk of developing HAM/TSP or HTLV-1 provirus load.
      All Iranian subjects possessed tax subgroup A sequences, and the protective
      effects of HLA-A*02 were observed only in Kagoshima subjects with tax subgroup B
      but not in those with tax subgroup A. Both the prevalence of HTLV-1 subgroups and
      the host genetic background may explain the different risks levels for HAM/TSP
      development in these two populations.

PMID- 15722540
TI  - Real-time reverse transcriptase PCR for the endogenous koala retrovirus reveals
      an association between plasma viral load and neoplastic disease in koalas.
AB  - Koala retrovirus (KoRV) is a newly described endogenous retrovirus and is unusual
      in that inserts comprise a full-length replication competent genome. As koalas
      are known to suffer from an extremely high incidence of leukaemia/lymphoma, the
      association between this retrovirus and disease in koalas was examined. Using
      quantitative real-time reverse transcriptase PCR it was demonstrated that KoRV
      RNA levels in plasma are significantly increased in animals suffering from
      leukaemia or lymphoma when compared with healthy animals. Increased levels of
      KoRV were also seen for animals with clinical chlamydiosis. A significant
      positive association between viral RNA levels and age was also demonstrated. Real
      time PCR demonstrated as much as 5 log variation in KoRV proviral DNA levels in
      genomic DNA extracted from whole blood from different animals. Taken together
      these data indicate that KoRV is an active endogenous retrovirus and suggests
      that it may be causally linked to neoplastic disease in koalas.

PMID- 15722541
TI  - Isolation and identification of a new tetravirus from Dendrolimus punctatus
      larvae collected from Yunnan Province, China.
AB  - In this study, Dendrolimus punctatus tetravirus (DpTV) has been identified as a
      new member of the genus Omegatetravirus of the family Tetraviridae that may be
      related serologically to Nudaurelia capensis omega virus (NomegaV). DpTV
      particles are isometric, with a diameter of about 40 nm and a buoyant density of
      1.281 g cm(-3) in CsCl. The virus has two capsid proteins (of 62 500 and 6800 Da)
      and two single-stranded RNA molecules (RNA1 and RNA2), which are 5492 and 2490 nt
      long, respectively. RNA1 has a large open reading frame (ORF) encoding a
      polypeptide of 180 kDa; RNA2 contains two partially overlapping ORFs encoding
      polypeptides of 17 and 70 kDa. The 180 kDa protein, which contains consensus
      motifs of a putative methyltransferase, helicase and RNA-dependent RNA
      polymerase, shows significant similarity to those of other tetraviruses. The 17
      kDa protein is a PEST (Pro/Glu/Ser/Thr) protein of unknown function. The 70 kDa
      protein is the coat protein precursor and is predicted to be cleaved at an Asn
      Phe site located after residue 570. The 70 kDa protein shows 86 and 66 % identity
      to its homologues in NomegaV and Helicoverpa armigera stunt virus, respectively.
      Secondary-structure analysis revealed that the RNAs of DpTV have tRNA-like
      structures at their 3' termini.

PMID- 15722542
TI  - An intact RBR-binding motif is not required for infectivity of Maize streak virus
      in cereals, but is required for invasion of mesophyll cells.
AB  - The replication-associated protein (RepA) of Maize streak virus interacts in
      yeast with retinoblastoma-related protein (RBR), the negative regulator of cell
      cycle progression. This may allow geminiviruses to subvert cell-cycle control to
      provide an environment that is suitable for viral DNA replication. To determine
      the importance of this interaction for MSV infection, the RBR-binding motif,
      LxCxE, was mutated to IxCxE or LxCxK. Whilst RBR binding in yeast could not be
      detected for the LxCxK mutant, the IxCxE protein retained limited binding
      activity. Both mutants were able to replicate in maize cultures and to infect
      maize plants. However, whereas the wild-type virus invaded mesophyll cells of
      mature leaves, the LxCxK mutant was restricted to the vasculature, which is
      invaded prior to leaf maturity. Mature leaves contain high levels of RBR and it
      is suggested that the MSV RepA-RBR interaction is essential only in tissues with
      high levels of active RBR.

PMID- 15722543
TI  - A three-nucleotide mutation altering the Maize streak virus Rep pRBR-interaction
      motif reduces symptom severity in maize and partially reverts at high frequency
      without restoring pRBR-Rep binding.
AB  - Geminivirus infectivity is thought to depend on interactions between the virus
      replication-associated proteins Rep or RepA and host retinoblastoma-related
      proteins (pRBR), which control cell-cycle progression. It was determined that the
      substitution of two amino acids in the Maize streak virus (MSV) RepA pRBR
      interaction motif (LLCNE to LLCLK) abolished detectable RepA-pRBR interaction in
      yeast without abolishing infectivity in maize. Although the mutant virus was
      infectious in maize, it induced less severe symptoms than the wild-type virus.
      Sequence analysis of progeny viral DNA isolated from infected maize enabled
      detection of a high-frequency single-nucleotide reversion of C(601)A in the 3 nt
      mutated sequence of the Rep gene. Although it did not restore RepA-pRBR
      interaction in yeast, sequence-specific PCR showed that, in five out of eight
      plants, the C(601)A reversion appeared by day 10 post-inoculation. In all plants,
      the C(601)A revertant eventually completely replaced the original mutant
      population, indicating a high selection pressure for the single-nucleotide
      reversion. Apart from potentially revealing an alternative or possibly additional
      function for the stretch of DNA that encodes the apparently non-essential pRBR
      interaction motif of MSV Rep, the consistent emergence and eventual dominance of
      the C(601)A revertant population might provide a useful tool for investigating
      aspects of MSV biology, such as replication, mutation and evolution rates, and
      complex population phenomena, such as competition between quasispecies and
      population turnover.

PMID- 15722544
TI  - Genetic diversity of a natural population of Cucurbit yellow stunting disorder
      virus.
AB  - An analysis of nucleotide sequences in five coding and one non-coding genomic
      regions of 35 Cucurbit yellow stunting disorder virus (CYSDV) isolates collected
      on a local scale over an 8 year period is reported here. In total, 2277 nt were
      sequenced for each isolate, representing about 13 % of the complete virus genome.
      Mean nucleotide diversity for the whole population in synonymous positions in the
      coding regions was 0.00068, whilst in the 5' untranslated region (5' UTR) of
      genomic RNA2, it was 0.00074; both of these values are very small, compared with
      estimates of nucleotide diversity for populations of other plant viruses.
      Nucleotide diversity was also determined independently for each of the ORFs and
      for the 5' UTR of RNA2; the data showed that variability is not distributed
      evenly among the different regions of the viral genome, with the coat protein
      gene showing more diversity than the other four coding regions that were
      analysed. However, the low variability found precluded any inference of selection
      differences among gene regions. On the other hand, no evidence of selection
      associated with host adaptation was found. In contrast, at least a single amino
      acid change in the coat protein appears to have been selected with time.

PMID- 15722545
TI  - Analysis of tombusvirus revertants to identify essential amino acid residues
      within RNA-dependent RNA polymerase motifs.
AB  - The RNA-dependent RNA polymerase (RdRp) of Tomato bushy stunt virus (TBSV)
      contains an arginine- and proline-rich (RPR) motif. This motif functions as an
      RNA-binding domain and is essential for tombusvirus replication. A mutant
      carrying three arginine substitutions in this motif rendered the virus unable to
      replicate in Nicotiana benthamiana plants and protoplasts. When the replicase
      function was provided in trans, by expressing the TBSV RdRp in N. benthamiana
      plants, an infectious variant could be isolated. Sequence analysis showed that
      only the substituted glycine residue (position 216) had reverted to arginine; all
      other substitutions remained unchanged. This finding suggested that strong
      selection pressure is active to maintain necessary sequences of the viral RdRp
      and that the analysis of revertants may help to identify essential viral
      functions.

PMID- 15722546
TI  - Phenotype of disease-associated PrP accumulation in the brain of bovine
      spongiform encephalopathy experimentally infected sheep.
AB  - In view of the established link between bovine spongiform encephalopathy (BSE)
      and variant Creutzfeldt-Jakob disease and of the susceptibility of sheep to
      experimental BSE, the detection of potential cases of naturally occurring BSE in
      sheep has become of great importance. In this study, the immunohistochemical
      (IHC) phenotype of disease-associated prion protein (PrP(d)) accumulation has
      been determined in the brain of 64 sheep, of various breeds and PrP genotypes,
      that had developed neurological disease after experimental BSE challenge with
      different inocula by a range of routes. Sheep BSE was characterized by neuron
      associated intra- and extracellular PrP(d) aggregates and by conspicuous and
      consistent deposits in the cytoplasm of microglia-like cells. The stellate PrP(d)
      type was also prominent in most brain areas and marked linear deposits in the
      striatum and midbrain were distinctive. Sheep of the ARR/ARR and ARQ/AHQ
      genotypes displayed lower levels of PrP(d) than other sheep, and intracerebral
      BSE challenge resulted in higher levels of PrP(d) accumulating in the brain
      compared with other routes. The PrP genotype and the route of challenge also
      appeared to affect the incubation period of the disease, giving rise to complex
      combinations of magnitude of PrP(d) accumulation and incubation period. Despite
      these differences, the phenotype of PrP(d) accumulation was found to be very
      consistent across the different factors tested (notably after subpassage of BSE
      in sheep), thus highlighting the importance of detailed IHC examination of the
      brain of clinically affected sheep for the identification of potential naturally
      occurring ovine BSE.

PMID- 15722547
TI  - Immunohistochemical characteristics of disease-associated PrP are not altered by
      host genotype or route of inoculation following infection of sheep with bovine
      spongiform encephalopathy.
AB  - It has previously been reported that disease-associated prion protein (PrP(d))
      derived from natural scrapie and from sheep infected experimentally with bovine
      spongiform encephalopathy (BSE) differed in respect of their immunohistochemical
      and immunoblotting properties. For BSE, however, these initial observations were
      restricted to orally challenged sheep of the ARQ/ARQ PrP genotype. Here, extended
      examinations were performed on 28 sheep that developed neurological signs after
      BSE experimental infection by one of three routes. Intracerebrally infected
      ARQ/ARQ sheep showed more widespread and abundant accumulations of PrP(d) in
      tissues of the lymphoreticular system (LRS) than VRQ/VRQ animals, whereas no
      peripheral PrP(d) was detected in ARR/ARR sheep. The intensity and dissemination
      of PrP(d) accumulation in LRS tissues were less than those found previously in
      orally dosed sheep. AHQ/AHQ sheep challenged orally and ARQ/AHQ and ARQ/ARQ
      animals infected intravenously showed similar LRS-tissue PrP(d) distributions and
      levels to those of ARQ/ARQ sheep infected intracerebrally. The patterns of intra-
      and extracellular immunoreactivity to different PrP antibodies in brain and LRS
      tissues and the immunoblotting characteristics of PrP(res) from brain samples
      remained constant, irrespective of the route of inoculation and the PrP genotype,
      and were the same as described previously for ARQ/ARQ sheep dosed orally with
      BSE. These results suggest that the intracellular truncation of BSE PrP(d) and
      the proteinase K cleavage site of BSE PrP(res) are not altered by PrP genotype or
      by route of inoculation and that, therefore, screening tests based on these
      properties can be applied to identify potential sheep BSE cases occurring
      naturally.

PMID- 15722548
TI  - Polygenic variation and transmission factors involved in the
      resistance/susceptibility to scrapie in a Romanov flock.
AB  - Data from 4049 Romanov sheep belonging to a flock affected by natural scrapie
      were analysed by using survival-analysis techniques. Failure time was defined as
      the period of time between first exposure to infection and the date that animals
      left the flock with scrapie signs. Four hundred and forty-seven sheep were
      identified as 'scrapie animals'. Several models, including level of exposure as a
      time-dependent effect, PrP genotype, sex, age at first exposure, litter size and
      factors related to vertical transmission, were tested. The best model was
      extended to a sire-dam frailty model, in order to estimate the polygenic
      variation in addition to that in the Prnp gene. A combined effect of rearing type
      and the dam's disease status was detected. Thus, only sheep with a low degree of
      exposure to infection as lambs (lambs reared artificially and born out of a
      healthy dam) showed less risk than others. Animals first exposed to infection at
      older ages seemed to be less susceptible to scrapie. In this Romanov population,
      new genotypes (AHQ/AHQ, AHQ/VRQ, ARR/VRQ and ARR/ARQ) were associated with risk,
      suggesting the effect of genotypes on the incubation period of animals. Polygenic
      variance was responsible for 21 % of the total genetic variability that was
      related to susceptibility to scrapie. Therefore, the genetic susceptibility to
      scrapie may be explained by the joint effect of point mutations at the Prnp major
      gene and a number of genes that modulate its effect.

PMID- 15722549
TI  - Polymorphisms at codons 108 and 189 in murine PrP play distinct roles in the
      control of scrapie incubation time.
AB  - Susceptibility to transmissible spongiform encephalopathies (TSEs) is associated
      strongly with PrP polymorphisms in humans, sheep and rodents. In mice, scrapie
      incubation time is controlled by polymorphisms at PrP codons 108 (leucine or
      phenylalanine) and 189 (threonine or valine), but the precise role of each
      polymorphism in the control of disease is unknown. The L108F and T189V
      polymorphisms are present in distinct structural regions of PrP and thus provide
      an excellent model with which to investigate the role of PrP structure and gene
      variation in TSEs. Two unique lines of transgenic mice, in which 108F and 189V
      have been targeted separately into the endogenous murine Prnp(a) gene, have been
      produced. TSE inoculation of inbred lines of mice expressing all allelic
      combinations at codons 108 and 189 has revealed a complex relationship between
      PrP allele and incubation time. It has been established that both codons 108 and
      189 control TSE incubation time, and that each polymorphism plays a distinct role
      in the disease process. Comparison of ME7 incubation times in mouse lines that
      are heterozygous at both codons has also identified a previously unrecognized
      intramolecular interaction between PrP codons 108 and 189.

PMID- 15722550
TI  - An enzyme-detergent method for effective prion decontamination of surgical steel.
AB  - Prions, transmissible agents that cause Creutzfeldt-Jakob disease (CJD) and other
      prion diseases, are known to resist conventional sterilization procedures.
      Iatrogenic transmission of classical CJD via neurosurgical instruments is well
      documented and the involvement of lymphoreticular tissues in variant CJD (vCJD),
      together with the unknown population prevalence of asymptomatic vCJD infection,
      has led to concerns about transmission from a wide range of surgical procedures.
      To address this problem, conditions were sought that destroy PrP(Sc) from vCJD
      infected human tissue and eradicate RML prion infectivity adsorbed onto surgical
      steel. Seven proteolytic enzymes were evaluated individually and in pairs at a
      range of temperatures and pH values and the additional effects of detergents,
      lipases and metal ions were assessed. A combination of proteinase K and Pronase,
      in conjunction with SDS, was shown to degrade PrP(Sc) material from highly
      concentrated vCJD-infected brain preparations to a level below detection. When
      RML prion-infected wires were exposed to the same enzymic treatment,
      intracerebral bioassay in highly susceptible hosts showed virtually no
      infectivity. The prion-degrading reagents identified in this study are readily
      available, inexpensive, non-corrosive to instruments, non-hazardous to staff and
      compatible with current equipment and procedures used in hospital sterilization
      units.

PMID- 15722551
TI  - Role of histone deacetylation in cell-specific expression of endothelial nitric
      oxide synthase.
AB  - Histone acetylation plays an important role in chromatin remodeling and gene
      expression. The molecular mechanisms involved in cell-specific expression of
      endothelial nitric-oxide synthase (eNOS) are not fully understood. In this study
      we investigated whether histone deacetylation was involved in repression of eNOS
      expression in non-endothelial cells. Induction of eNOS expression by histone
      deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate was
      observed in all four different types of non-endothelial cells examined. Chromatin
      immunoprecipitation assays showed that the induction of eNOS expression by TSA
      was accompanied by a remarkable increase of acetylation of histone H3 associated
      with the eNOS 5'-flanking region in the non-endothelial cells. Moreover, DNA
      methylation-mediated repression of eNOS promoter activity was partially reversed
      by TSA treatment, and combined treatment of TSA and 5-aza-2'-deoxycytidine
      (AzadC) synergistically induced eNOS expression in non-endothelial cells. The
      proximal Sp1 site is critical for basal activity of eNOS promoter. The induction
      of eNOS by inhibition of HDACs in non-endothelial cells, however, appeared not
      mediated by the changes in Sp1 DNA binding activity. We further showed that Sp1
      bound to the endogenous eNOS promoter and associated with HDAC1 in non
      endothelial HeLa cells. Combined TSA and AzadC treatment increased Sp1 binding to
      the endogenous eNOS promoter but decreased the association between HDAC1 and Sp1
      in HeLa cells. Our data suggest that HDAC1 plays a critical role in eNOS
      repression, and the proximal Sp1 site may serve a key target for HDCA1-mediated
      eNOS repression in non-endothelial cells.

PMID- 15722552
TI  - Cloning and characterization of mouse E2F8, a novel mammalian E2F family member
      capable of blocking cellular proliferation.
AB  - The E2F transcription factor family plays a crucial and well established role in
      cell cycle progression. Deregulation of E2F activities in vivo leads to
      developmental defects and cancer. Based on current evidence in the field,
      mammalian E2Fs can be functionally categorized into either transcriptional
      activators (E2F1, E2F2, and E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6, and
      E2F7). We have identified a novel E2F family member, E2F8, which is conserved in
      mice and humans and has its counterpart in Arabidopsis thaliana (E2Ls).
      Interestingly, E2F7 and E2F8 share unique structural features that distinguish
      them from other mammalian E2F repressor members, including the presence of two
      distinct DNA-binding domains and the absence of DP-dimerization, retinoblastoma
      binding, and transcriptional activation domains. Similar to E2F7, overexpression
      of E2F8 significantly slows down the proliferation of primary mouse embryonic
      fibroblasts. These observations, together with the fact that E2F7 and E2F8 can
      homodimerize and are expressed in the same adult tissues, suggest that they may
      have overlapping and perhaps synergistic roles in the control of cellular
      proliferation.

PMID- 15722553
TI  - Identification of direct genomic targets downstream of the nuclear factor-kappaB
      transcription factor mediating tumor necrosis factor signaling.
AB  - Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that controls
      expression of inflammatory genetic networks. Although the nuclear factor-kappaB
      (NF-kappaB) pathway is crucial for mediating cellular TNF responses, the complete
      spectrum of NF-kappaB-dependent genes is unknown. In this study, we used a
      tetracycline-regulated cell line expressing an NF-kappaB inhibitor to
      systematically identify NF-kappaB-dependent genes. A microarray data set
      generated from a time course of TNF stimulation in the presence or absence of NF
      kappaB signaling was analyzed. We identified 50 unique genes that were regulated
      by TNF (Pr(F)<0.001) and demonstrated a change in signal intensity of+/-3-fold
      relative to control. Of these, 28 were NF-kappaB-dependent, encoding proteins
      involved in diverse cellular activities. Quantitative real-time PCR assays of
      eight characterized NF-kappaB-dependent genes and five genes not previously known
      to be NF-kappaB-dependent (Gro-beta and-gamma, IkappaBepsilon, interleukin (IL)
      7R, and Naf-1) were used to determine whether they were directly or indirectly NF
      kappaB regulated. Expression of constitutively active enhanced green
      fluorescent.NF-kappaB/Rel A fusion protein transactivated all but IL-6 and IL-7R
      in the absence of TNF stimulation. Moreover, TNF strongly induced all 12 genes in
      the absence of new protein synthesis. High probability NF-kappaB sites in novel
      genes were predicted by binding site analysis and confirmed by electrophoretic
      mobility shift assay. Chromatin immunoprecipitation assays show the endogenous
      IkappaBalpha/epsilon, Gro-beta/gamma, and Naf-1 promoters directly bound NF
      kappaB/Rel A in TNF-stimulated cells. Together, these studies systematically
      identify the direct NF-kappaB-dependent gene network downstream of TNF signaling,
      extending our knowledge of biological processes regulated by this pathway.

PMID- 15722554
TI  - Differences in gene expression between wild type and Hoxa1 knockout embryonic
      stem cells after retinoic acid treatment or leukemia inhibitory factor (LIF)
      removal.
AB  - Homeobox (Hox) genes encode a family of transcription factors that regulate
      embryonic patterning and organogenesis. In embryos, alterations of the normal
      pattern of Hox gene expression result in homeotic transformations and
      malformations. Disruption of the Hoxa1 gene, the most 3' member of the Hoxa
      cluster and a retinoic acid (RA) direct target gene, results in abnormal
      ossification of the skull, hindbrain, and inner ear deficiencies, and neonatal
      death. We have generated Hoxa1(-/-) embryonic stem (ES) cells (named Hoxa1-15)
      from Hoxa1(-/-) mutant blastocysts to study the Hoxa1 signaling pathway. We have
      characterized in detail these Hoxa1(-/-) ES cells by performing microarray
      analyses, and by this technique we have identified a number of putative Hoxa-1
      target genes, including genes involved in bone development (e.g. Col1a1,
      Postn/Osf2, and the bone sialoprotein gene or BSP), genes that are expressed in
      the developing brain (e.g. Nnat, Wnt3a, BDNF, RhoB, and Gbx2), and genes involved
      in various cellular processes (e.g. M-RAS, Sox17, Cdkn2b, LamA1, Col4a1, Foxa2,
      Foxq1, Klf5, and Igf2). Cell proliferation assays and Northern blot analyses of a
      number of ES cell markers (e.g. Rex1, Oct3/4, Fgf4, and Bmp4) suggest that the
      Hoxa1 protein plays a role in the inhibition of cell proliferation by RA in ES
      cells. Additionally, Hoxa1(-/-) ES cells express high levels of various
      endodermal markers, including Gata4 and Dab2, and express much less Fgf5 after
      leukemia inhibitory factor (LIF) withdrawal. Finally, we propose a model in which
      the Hoxa1 protein mediates repression of endodermal differentiation while
      promoting expression of ectodermal and mesodermal characteristics.

PMID- 15722555
TI  - Depletion of human micro-RNA miR-125b reveals that it is critical for the
      proliferation of differentiated cells but not for the down-regulation of putative
      targets during differentiation.
AB  - Micro-RNAs are small non-coding RNAs that regulate target gene expression post
      transcriptionally through base pairing with the target messenger RNA. Functional
      characterization of micro-RNAs awaits robust experimental methods to knock-down a
      micro-RNA as well as to assay its function in vivo. In addition to the recently
      developed method to sequester micro-RNA with 2'-O-methyl antisense
      oligonucleotide, we report that small interfering RNA against the loop region of
      a micro-RNA precursor can be used to deplete the micro-RNA. The depletion of miR
      125b by this method had a profound effect on the proliferation of adult
      differentiated cancer cells, and this proliferation defect was rescued by co
      transfected mature micro-RNA. This technique has unique advantages over the 2'-O
      methyl antisense oligonucleotide and can be used to determine micro-RNA function,
      assay micro-RNAs in vivo, and identify the contribution of a predicted micro-RNA
      precursor to the pool of mature micro-RNA in a given cell. miR-125b and let-7
      micro-RNAs are induced, whereas their putative targets, lin-28 and lin-41, are
      decreased during in vitro differentiation of Tera-2 or embryonic stem cells.
      Experimental increase or decrease of micro-RNA concentrations did not, however,
      affect the levels of the targets, a finding that is explained by the fact that
      the down-regulation of the targets appears to be mostly at the transcriptional
      level in these in vitro differentiation systems. Collectively these results
      reveal the importance of micro-RNA depletion strategies for directly determining
      micro-RNA function in vivo.

PMID- 15722557
TI  - Mad1 function in cell proliferation and transcriptional repression is antagonized
      by cyclin E/CDK2.
AB  - The transcription factors of the Myc/Max/Mad network play essential roles in the
      regulation of cellular behavior. Mad1 inhibits cell proliferation by recruiting
      an mSin3-corepressor complex that contains histone deacetylase activity. Here we
      demonstrate that Mad1 is a potent inhibitor of the G(1) to S phase transition, a
      function that requires Mad1 to heterodimerize with Max and to bind to the
      corepressor complex. Cyclin E/CDK2, but not cyclin D and cyclin A complexes,
      fully restored S phase progression. In addition inhibition of colony formation
      and gene repression by Mad1 were also efficiently antagonized by cyclin E/CDK2.
      This was the result of cyclin E/CDK2 interfering with the interaction of Mad1
      with HDAC1 and reducing HDAC activity. Our findings define a novel interplay
      between the cell cycle regulator cyclin E/CDK2 and Mad1 and its associated
      repressor complex and suggests an additional mechanism how cyclin E/CDK2 affects
      the G(1) to S phase transition.

PMID- 15722556
TI  - Transcriptional Co-activators CREB-binding protein/p300 increase chondrocyte Cd
      rap gene expression by multiple mechanisms including sequestration of the
      repressor CCAAT/enhancer-binding protein.
AB  - Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a small secreted
      matrix protein expressed in developing and adult cartilage and by chondrocytes in
      culture. We have previously shown that the expression of Cd-rap, like many other
      cartilage matrix proteins, is repressed by interleukin 1beta and that the
      transcription factor CCAAT/enhancer-binding protein (C/EBP) beta plays an
      important role in the interleukin 1beta-induced repression (Okazaki, K., Li, J.,
      Yu, H., Fukui, N., and Sandell, L. J. (2002) J. Biol. Chem. 277, 31526-31533).
      The co-activators CREB-binding protein (CBP) and p300 are transcriptional co
      regulators that participate in the activities of many different transcription
      factors including C/EBP. Here we show that CBP/p300 can reverse the inhibitory
      effect of C/EBP and moreover can stimulate expression of Cd-rap. The mechanism of
      this effect is shown to involve a unique synergy whereby CBP/p300 stimulate Cd
      rap gene expression by at least two mechanisms. First, binding of CBP/p300 to
      C/EBPbeta leads to sequestration of C/EBP eliminating DNA binding and subsequent
      repression; second, binding of CBP/p300 to the transcriptional activator Sox9
      increases Sox9 DNA binding to the Cd-rap promoter leading to further stimulation
      of gene transcription. This is an example of a complementary transcriptional
      network whereby two very different mechanisms act together to confer a functional
      increase in transcription. This new paradigm is likely generally applicable to
      cartilage genes as Col2a1 cartilage collagen gene responds similarly.

PMID- 15722558
TI  - Thematic review series: The immune system and atherogenesis. Lipoprotein
      associated inflammatory proteins: markers or mediators of cardiovascular disease?
AB  - In humans, a chronically increased circulating level of C-reactive protein (CRP),
      a positive acute-phase reactant, is an independent risk factor for cardiovascular
      disease. This observation has led to considerable interest in the role of
      inflammatory proteins in atherosclerosis. In this review, after discussing CRP,
      we focus on the potential role in the pathogenesis of human vascular disease of
      inflammation-induced proteins that are carried by lipoproteins. Serum amyloid A
      (SAA) is transported predominantly on HDL, and levels of this protein increase
      markedly during acute and chronic inflammation in both animals and humans.
      Increased SAA levels predict the risk of cardiovascular disease in humans. Recent
      animal studies support the proposal that SAA plays a role in atherogenesis.
      Evidence is accruing that secretory phospholipase A(2), an HDL-associated
      protein, and platelet-activating factor acetylhydrolase, a protein associated
      predominantly with LDL in humans and HDL in mice, might also play roles both as
      markers and mediators of human atherosclerosis. In contrast to positive acute
      phase proteins, which increase in abundance during inflammation, negative acute
      phase proteins have received less attention. Apolipoprotein A-I (apoA-I), the
      major apolipoprotein of HDL, decreases during inflammation. Recent studies also
      indicate that HDL is oxidized by myeloperoxidase in patients with established
      atherosclerosis. These alterations may limit the ability of apoA-I to participate
      in reverse cholesterol transport. Paraoxonase-1 (PON1), another HDL-associated
      protein, also decreases during inflammation. PON1 is atheroprotective in animal
      models of hypercholesterolemia. Controversy over its utility as a marker of human
      atherosclerosis may reflect the fact that enzyme activity rather than blood level
      (or genotype) is the major determinant of cardiovascular risk. Thus, multiple
      lipoprotein-associated proteins that change in concentration during acute and
      chronic inflammation may serve as markers of cardiovascular disease. In future
      studies, it will be important to determine whether these proteins play a causal
      role in atherogenesis.

PMID- 15722559
TI  - RAW264.7 cells lack prostaglandin-dependent autoregulation of tumor necrosis
      factor-alpha secretion.
AB  - Studies of the response of RAW264.7 cells (RAW) to lipopolysaccharide (LPS) were
      carried out to determine why these cells do not demonstrate the prostaglandin
      (PG)-dependent autocrine regulation of tumor necrosis factor-alpha (TNF-alpha)
      secretion observed in primary resident peritoneal macrophages (RPMs). The major
      cyclooxygenase (COX) product of LPS-stimulated RAW was PGD2, with lesser amounts
      of PGE2. LPS-treated RAW produced PGs more slowly and reached their maximal PG
      synthetic rate later than did LPS-treated RPMs, as a result of lower constitutive
      COX-1 expression and a slower rate of COX-2 induction. Cytosolic phospholipase A2
      and levels of free arachidonic acid were similar in RAW and RPMs. In contrast to
      RPMs, LPS-treated RAW produced high quantities of TNF-alpha, which were not
      altered in the presence of COX inhibitors. This failure of endogenous PGs to
      suppress TNF-alpha secretion was explained by the absence of the prostaglandin D2
      receptor and the low levels of PGE2 produced during the first 2 h of the LPS
      response. These studies demonstrate that autocrine regulation of TNF-alpha
      secretion in response to LPS is greatly facilitated by a COX-1-mediated rapid
      accumulation of PGs as well by a correspondence between the PGs produced and the
      receptors expressed by the cells.

PMID- 15722560
TI  - Endothelial lipase is inactivated upon cleavage by the members of the proprotein
      convertase family.
AB  - Mature endothelial lipase (EL) is a 68 kDa glycoprotein. In HepG2 cells infected
      with adenovirus encoding human EL, the mature EL was detectable in the cell
      lysates and heparin-releasable fractions. In contrast, cell media of these cells
      contained two EL fragments: an N-terminal 40 kDa fragment and a C-terminal 28 kDa
      fragment. N-terminal protein sequencing of the His-tagged 28 kDa fragment
      revealed that EL is cleaved on the C terminus of the sequence RNKR330, the
      consensus cleavage sequence for mammalian proprotein convertases (pPCs).
      Replacement of Arg-330 with Ser by site-directed mutagenesis totally abolished EL
      processing. EL processing could efficiently be attenuated by specific inhibitors
      of pPCs, alpha1-antitrypsin Portland (alpha1-PDX) and alpha1-antitrypsin variant
      AVRR. Coexpression of the pPCs furin, PC6A, and PACE4 with EL resulted in a
      complete conversion of the full-length EL to a truncated 40 kDa fragment.
      Exogenously added EL was also processed by cells, and the processing could be
      attenuated by alpha1-PDX. The expressed N-terminal 40 kDa fragment of EL (EL-40)
      harboring the catalytic site failed to hydrolyze [14C]NEFA from [14C]dipalmitoyl
      PC-labeled HDL. EL-40 was incapable of bridging 125I-labeled HDL to the cells and
      had no impact on plasma lipid concentration when overexpressed in mice. Thus, our
      results demonstrate that pPCs are involved in the inactivation process of EL.

PMID- 15722561
TI  - Phosphocholine as a pattern recognition ligand for CD36.
AB  - We have previously shown that CD36 recognizes oxidation products of phospholipids
      on oxidized LDL (OxLDL) such as 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3
      phosphocholine (POVPC). The current study was designed to examine whether the
      phosphocholine (PC) headgroup in POVPC constitutes an obligatory binding target
      for CD36. To examine the contribution of PC in the binding of POVPC to CD36, we
      used well-defined synthetic oxidized phospholipids (OxPLs) cross-linked to BSA or
      to a hexapeptide. The OxPL adducts were then tested for their ability to bind to
      CD36-transfected cells and for their ability to inhibit OxLDL binding to CD36.
      Both POVPC-BSA and POVPC-peptide adducts were high-affinity ligands for CD36 and
      potent inhibitors of OxLDL binding. Enzymatic removal of the entire PC moiety of
      the POVPC-peptide, or of the choline headgroup alone, as well as substitution of
      the choline headgroup by ethanolamine abrogated the inhibitory activity of POVPC.
      Interestingly, PC by itself or cross-linked to BSA did not show any intrinsic
      competition activity. In conclusion, our data demonstrate that the PC headgroup
      of OxPL alone is sufficient for binding to CD36, but only if presented in the
      correct conformation as in OxPL of OxLDL or as in POVPC-peptide adducts.

PMID- 15722562
TI  - Thematic review series: the immune system and atherogenesis. Bridging the innate
      and adaptive immune systems.

PMID- 15722563
TI  - A comprehensive classification system for lipids.
AB  - Lipids are produced, transported, and recognized by the concerted actions of
      numerous enzymes, binding proteins, and receptors. A comprehensive analysis of
      lipid molecules, "lipidomics," in the context of genomics and proteomics is
      crucial to understanding cellular physiology and pathology; consequently, lipid
      biology has become a major research target of the postgenomic revolution and
      systems biology. To facilitate international communication about lipids, a
      comprehensive classification of lipids with a common platform that is compatible
      with informatics requirements has been developed to deal with the massive amounts
      of data that will be generated by our lipid community. As an initial step in this
      development, we divide lipids into eight categories (fatty acyls, glycerolipids,
      glycerophospholipids, sphingolipids, sterol lipids, prenol lipids,
      saccharolipids, and polyketides) containing distinct classes and subclasses of
      molecules, devise a common manner of representing the chemical structures of
      individual lipids and their derivatives, and provide a 12 digit identifier for
      each unique lipid molecule. The lipid classification scheme is chemically based
      and driven by the distinct hydrophobic and hydrophilic elements that compose the
      lipid. This structured vocabulary will facilitate the systematization of lipid
      biology and enable the cataloging of lipids and their properties in a way that is
      compatible with other macromolecular databases.

PMID- 15722564
TI  - Quantitation of rat liver vitamin E metabolites by LC-MS during high-dose vitamin
      E administration.
AB  - To evaluate vitamin E metabolism, a method was developed to quantitate liver
      alpha- and gamma-tocopherol metabolites, alpha-carboxyethyl hydroxychroman [alpha
      CEHC; 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman] and gamma-CEHC
      [2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman], respectively. Vitamin E
      supraenriched livers were obtained from rats that were injected with vitamin E
      daily for 18 days. Liver samples (approximately 50 mg) were homogenized,
      homogenate CEHC-conjugates were hydrolyzed, CEHCs were extracted with ethyl
      ether, and then CEHCs were quantitated using liquid chromatography-mass
      spectrometry (LC-MS). Precision, based on intersample variability, ranged from 1%
      to 3%. Recovery of alpha- and gamma-CEHCs added to liver homogenates ranged from
      77% to 87%. Detection limits of alpha- and gamma-CEHC were 20 fmol, with a linear
      detector response from 0.025 to 20 pmol injected. Corresponding with an increase
      in liver alpha-tocopherol, the MS peak for liver alpha-CEHC (mass-to-charge ratio
      277.8) increased 80-fold (0.18 +/- 0.01 to 15 +/- 2 nmol/g). Liver alpha-CEHC
      concentrations were correlated with serum alpha-CEHC, liver alpha-tocopherol, and
      serum alpha-tocopherol (P < 0.001 for each comparison). alpha-CEHC represented
      0.5-1% of the liver alpha-tocopherol concentration. Thus, LC-MS can be
      successfully used to quantitate alpha- and gamma-CEHC in liver samples. These
      data suggest that in times of excess liver alpha-tocopherol, increased metabolism
      of alpha-tocopherol to alpha-CEHC occurs.

PMID- 15722565
TI  - A simplified method for the preparation of detergent-free lipid rafts.
AB  - Lipid rafts are small plasma membrane domains that contain high levels of
      cholesterol and sphingolipids. Traditional methods for the biochemical isolation
      of lipid rafts involve the extraction of cells with nonionic detergents followed
      by the separation of a low-density, detergent-resistant membrane fraction on
      density gradients. Because of concerns regarding the possible introduction of
      artifacts through the use of detergents, it is important to develop procedures
      for the isolation of lipid rafts that do not involve detergent extraction. We
      report here a simplified method for the purification of detergent-free lipid
      rafts that requires only one short density gradient centrifugation, but yields a
      membrane fraction that is highly enriched in cholesterol and protein markers of
      lipid rafts, with no contamination from nonraft plasma membrane or intracellular
      membranes.

PMID- 15722566
TI  - Denaturing high-performance liquid chromatography in the detection of ABCA1 gene
      mutations in familial HDL deficiency.
AB  - Mutations in the ABCA1 gene are the cause of familial high density lipoprotein
      deficiency (FHD). Because these mutations are spread over the entire gene, their
      detection requires the sequencing of all 50 exons. The aim of this study was to
      validate denaturing high-performance liquid chromatography (DHPLC) in mutation
      detection as an alternative to systematic sequencing. Exons of the ABCA1 gene
      were amplified using primers employed for sequencing. Temperatures for DHPLC were
      deducted from a software and empirically defined for each amplicon. To assess
      DHPLC reliability, we tested 30 sequence variants found in FHD patients and
      controls. Combined DHPLC and sequencing was applied to the genotyping of new FHD
      patients. Most of the amplicons required from two to five temperature conditions
      to obtain partially denatured DNA over the entire amplicon length. Twenty-nine of
      the variants found by sequencing were detected by DHPLC (97% sensitivity). The
      detection of the last variant (in exon 40) required different primers and
      amplification conditions. DHPLC and sequencing analysis of new FHD patients
      revealed that all amplicons showing a heteroduplex DHPLC profile contained
      sequence variants. No variants were detected in amplicons with a homoduplex
      profile. DHPLC is a sensitive and reliable method for the detection of ABCA1 gene
      mutations.

PMID- 15722567
TI  - Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox
      mode electrochemical detection.
AB  - We describe a method for the determination of the two major urinary metabolites
      of vitamin K as the methyl esters of their aglycone structures, 2-methyl-3-(3'-3'
      carboxymethylpropyl)-1,4-naphthoquinone (5C-aglycone) and 2-methyl-3-(5'-carboxy
      3'-methyl-2'-pentenyl)-1,4-naphthoquinone (7C-aglycone), by HPLC with
      electrochemical detection (ECD) in the redox mode. Urinary salts were removed by
      reversed-phase (C18) solid-phase extraction (SPE), and the predominantly
      conjugated vitamin K metabolites were hydrolyzed with methanolic HCl. The
      resulting carboxylic acid aglycones were quantitatively methylated with
      diazomethane and fractionated by normal-phase (silica) SPE. Final analysis was by
      reversed-phase (C18) HPLC with a methanol-aqueous mobile phase. Metabolites were
      detected by amperometric, oxidative ECD of their quinol forms, which were
      generated by postcolumn coulometric reduction at an upstream electrode. The assay
      gave excellent linearity (typically, r2 > or = 0.999) and high sensitivity with
      an on-column detection limit of < 3.5 fmol (< 1 pg). The interassay precision was
      typically 10%. Metabolite recovery was compared with that of an internal standard
      [2-methyl-3-(7'-carboxy-heptyl)-1,4-naphthoquinone] added to urine samples just
      before analysis. Using this methodology, we confirmed that the 5C- and 7C
      aglycones were major catabolites of both phylloquinone (vitamin K1) and
      menaquinones (vitamin K2) in humans. We propose that the measurement of urinary
      vitamin K metabolite excretion is a candidate noninvasive marker of total vitamin
      K status.

PMID- 15722568
TI  - Mediator-lipidomics: databases and search algorithms for PUFA-derived mediators.
AB  - Lipid mediators (LMs) derived from PUFAs play important roles in health and
      disease. Databases and search algorithms are crucial, but currently unavailable,
      for accurate and prompt analysis of LMs via liquid chromatography-ultraviolet
      tandem mass spectrometry (LC-UV-MS/MS). A novel algorithm and databases,
      cognoscitive-contrast-angle algorithm and databases (COCAD), were developed for
      the identification of LMs based on the integration of standard MS/MS spectra with
      chromatograms and UV spectra. Segment naming and empirical fragmentation rules
      were introduced to determine MS/MS ion identities, along with ion intensities
      used by COCAD in matching the unknown to those of authentic standards. The
      structures of potential LMs without synthetic and/or authentic products as
      standards were identified by developing theoretical databases and algorithms
      based on virtual LC-UV-MS/MS spectra and chromatograms. The performance of these
      databases and algorithms was tested by identifying LMs in murine tissues. These
      results indicate that COCAD has many advantages for profiling and identification
      of LMs compared with the conventional dot-product algorithm.

PMID- 15722570
TI  - HLA-G upregulation in pre-malignant and malignant lesions of the gastrointestinal
      tract.
AB  - HLA-G belongs to the nonclassical MHC class Ib group of molecules and has been
      implicated in mediating immune-responsiveness in various cancerous and non
      cancerous cell types. We have examined HLA-G expression in a number of human
      gastrointestinal malignancies, including pancreatic ductal adenocarcinoma,
      ampullary cancer, biliary cancer, and colorectal cancer by immunolabeling
      analysis. We used indices of <5% (negative), 6-25%, 26-50%, 51-75%, and >75%
      (diffuse) to subclassify lesions based on percentage of positive cell labeling.
      Across all cancer subtypes, 52-79% of lesions demonstrated expression of HLA-G,
      with up to 33% of lesions demonstrating diffuse (>75%) expression. In addition,
      we utilized the neoplastic progression model of colorectal cancer to evaluate HLA
      G protein expression in normal colon, tubulovillous adenomas, invasive cancer,
      and liver metastases arising from colorectal cancer. Focal HLA-G expression was
      detected in regions of normal colon adjacent to sites of adenomatous and
      cancerous lesions, as well as in all stages of cancer progression. Overall, the
      percentage of diffusely (>75%) labeled lesions appeared increased in
      preneoplastic and neoplastic conditions, as compared to normal colon.
      Specifically, tubulovillous adnenomas demonstrated pronounced diffuse labeling in
      58% of lesions examined. No correlation with HLA-G expression and CD4+ or CD8+ T
      cells was identified. We propose that HLA-G expression is upregulated in a large
      percentage of gastrointestinal lesions and may serve to mediate immune
      responsiveness in certain instances.

PMID- 15722569
TI  - Photodynamic therapy for pancreatic and biliary tract carcinoma.
AB  - The prognosis of patients with pancreatic and biliary tract cancer treated with
      conventional therapies such as stent insertion or chemotherapy is often poor, and
      new approaches are urgently needed. Surgery is the only curative treatment but is
      appropriate in less than 20% of cases, and even then it is associated with a 5-yr
      survival of less than 30% in selected series. Photodynamic therapy represents a
      novel treatment for pancreaticobiliary malignancy. It is a way of producing
      localized tissue necrosis with light, most conveniently from a low-power, red
      laser, after prior administration of a photosensitizing agent, thereby initiating
      a non-thermal cytotoxic effect and tissue necrosis. This review outlines the
      mechanisms of action of photodynamic therapy including direct cell death,
      vascular injury, and immune system activation, and summarizes the results of
      preclinical and clinical studies of photodynamic therapy for pancreaticobiliary
      malignancy.

PMID- 15722571
TI  - p27kip1 expression is inversely related to the grade of gastric MALT lymphoma.
AB  - BACKGROUND: Decreased or lost expression of the cyclin-dependent kinase inhibitor
      p27kip1 protein has been found to be a poor prognostic factor in many cancers,
      including gastric cancer. AIM: To evaluate p27kip1 expression in gastric mucosa
      associated lymphoid tissue (MALT) and gastric B-cell lymphoma. METHODS: Fifty-two
      cases of gastric lymphoma, mean age 68.7 yr (range 23-90 yr), 11 of chronic
      Helicobacter pylori-associated gastritis, and 5 of normal gastric mucosa were
      studied. Patients were classified into two groups. Stage IE gastric lymphomas
      were defined as local gastric lymphoma of MALT and more advanced stages as
      advanced gastric lymphoma. Twenty-three patients diagnosed as stage IE, 13 of
      these were low-grade and 10 diffuse large B-cell lymphoma (DLBL). Twenty-nine
      patients were at stage IIE or above, 18 with low-grade and 11 with DLBL. Serial
      sections were evaluated by immunohistochemistry after staining with antibodies
      against p27/Kip1 and Ki-67. RESULTS: The proliferative index was higher in
      gastric DLBL than in low-grade MALT lymphomas, 57.1+/-31.2 vs 17.3+/-20.6
      (p=0.0001). The mean p27kip1 expression score for high-grade patients was
      significantly lower compared with that of low-grade patients, 0.5+/-0.4 and 1.6+/
      0.8, respectively (p=0.001). Comparative evaluation of p27kip1 expression in
      malignant lymphoid cells revealed that B cells of the localized gastric DLBL
      patients expressed the least p27kip1, 0.36+/-0.32. This value was lower than that
      of malignant lymphoid cells of patients with advanced DLBL, 0.64+/-0.53, advanced
      low-grade MALT lymphoma, 1.59+/-0.79, and localized low-grade MALT lymphoma,
      1.59+/-0.84. In the multivariate model in which all p27kip1 variables were
      entered, the expression of p27kip1 in malignant lymphoid cells was inversely
      correlated with the grade of the lymphoma irrespective of the stage of the
      disease (p=0.0001), and significantly predicted grade: OR:0.07, 95% CI 0.07-0.31,
      p=0.0001. CONCLUSION: p27kip1 may be a putative distinct molecular marker to
      differentiate between low-grade and high-grade gastric lymphoma.

PMID- 15722572
TI  - Clinical significance of K-ras and c-erbB-2 mutations in pancreatic
      adenocarcinoma and chronic pancreatitis.
AB  - BACKGROUND: The differentiation of chronic pancreatitis (CP) from pancreatic
      adenocarcinoma (PA) remains the great challenge for clinicians. The purpose of
      this study was to compare the prevalence of K-ras and c-erbB-2 mutations in PA
      and CP in order to evaluate their usefulness in differential diagnosis of those
      diseases. METHODS: The study included 49 patients who underwent Whipple resection
      or distal pancreatectomy for pancreatic adenocarcinoma (26 subjects) or chronic
      pancreatitis (23 subjects). DNA from pancreatic tissue was analyzed for K-ras
      codon 12 and c-erbB-2 mutations with PCR amplifications. RESULTS: The K-ras gene
      mutation has been shown in 20 (76.9%) PA cases and in 8 (34.8%) CP cases
      (p<0.01). Prevalence of c-erbB-2 amplification in patients with PA was 17
      (65.3%), which was not different from CP, 16 (56.5%) (p=0.58). There was a
      significant correlation between K-ras mutation and lymph node metastases
      (p=0.025) as well as between K-ras mutation and G3 tumor differentiation
      (p=0.037). Overall median survival in patients with PA was 9.5 mo. There was no
      relationship between presence of K-ras (p=0.58) or c-erbB-2 (p=0.17) mutation and
      survival time in PA patients. CONCLUSION: Those results may indicate that both K
      ras and c-erbB-2 play a role in pancreatic carcinogenesis, however only K-ras may
      provide an additional tool in differential diagnosis of CP and PC.

PMID- 15722573
TI  - Clinicopathological comparison between young and old age patients with gastric
      adenocarcinoma.
AB  - BACKGROUND: There are controversies regarding the differences in the
      clinicopathological characteristics of gastric cancer between young and older
      patients. Our aim was to establish clinicopathological differences between both
      groups. PATIENTS AND METHODS: Records of all Jordanian patients with gastric
      adenocarcinoma managed at our hospitals between 1991 and 2001 were reviewed.
      Patients were divided into two groups according to their age; young patients
      (<or=40 yr of age; n=17), and older patients (>40 yr of age; n=159). The
      clinicopathological features and overall survival data for both groups were
      retrospectively analyzed and compared. RESULTS: In the young group, in comparison
      with older group, females were more predominant (p=0.049), family history of
      gastric cancer was more common (p=0.006), proximal location and involvement of
      the entire stomach were more (p<0.001), and diffuse cancers (65% vs 13%) and
      poorly differentiated carcinomas (47% vs 26%) were more prevalent. Advanced tumor
      stage was the same in both groups (65% vs 64%, ns). There was no significant
      difference in survival between young and old patients (p=0.287). However, age was
      significantly associated with survival when treated as a continuous variable even
      after adjusting for the effects of site and stage of tumor on survival. The
      probability of death was increased by 5.6% with each yr of age. CONCLUSIONS:
      Special features of gastric cancer differ significantly between young and older
      age groups. Greater awareness of early-onset gastric cancer is mandatory for
      detecting cancer early enough so that it is treated successfully.

PMID- 15722574
TI  - Survivin overexpression in hepatocellular carcinoma is associated with p53
      dysregulation.
AB  - BACKGROUND: Survivin is a recently described anti-apoptotic protein that is
      suppressed by wild-type p53 and is overexpressed in 41-70% of hepatocellular
      carcinomas from Asia. Two alternatively spliced transcripts have also been
      described: anti-apoptotic survivin-DeltaEx3 and non-anti-apoptotic survivin-2B.
      Survivin splice variant expression has not been studied in HCC, and little is
      known about survivin expression in hepatocellular carcinomas arising in other
      parts of the world, where risk factors are often different than they are in Asia.
      AIM OF THE STUDY: We studied survivin mRNA and protein expression in a United
      States cohort of hepatocellular carcinomas and correlated the findings with p53
      immunopositivity. METHODS: RT-PCR was performed for survivin, survivin-2B, and
      survivin-DeltaEx3 in 20 HCCs and one intrahepatic cholangiocarcinoma. Expression
      levels of total survivin were evaluated with real-time PCR. Protein expression
      was examined by immunohistochemistry. RESULTS: Survivin was the major transcript,
      and all transcripts were present in all normal and neoplastic tissues; 11/20
      (55%) HCCs and the one cholangiocarcinoma showed twofold or greater
      overexpression of survivin. Next, we examined survivin and p53 protein expression
      by immunohistochemistry on a separate series of 79 HCC, 13 fibrolamellar
      carcinomas, and 15 hepatic adenomas; 14/79 (17%) HCC, but none of the
      fibrolamellar carcinomas or hepatic adenomas, showed survivin protein
      overexpression, and 25/79 HCC (32%) showed abnormal nuclear accumulation of p53,
      which correlated with increased survivin expression. CONCLUSIONS: All three
      survivin transcripts are present in normal liver and HCC. Survivin is the
      dominant transcript in HCC and is overexpressed in 55% of cases. Survivin protein
      overexpression is associated with aberrant p53 nuclear positivity.

PMID- 15722575
TI  - Do the progesterone receptors have a role to play in gallbladder cancer?
AB  - BACKGROUND: Gallstone disease as well as gallbladder cancer are more common in
      women and female sex hormones may be involved in their etiology. AIM AND METHODS:
      To determine whether female sex hormones have a role in the pathogenesis, of
      gallbladder carcinoma and in its prognosis, we estimated, by enzyme immunoassay,
      the estrogen and progesterone receptors (ER and PgR) in the gallbladders of 21
      patients with gallbladder cancer, 19 patients with cholelithiasis, and 6 patients
      who underwent incidental removal of essentially normal gallbladder as a component
      of wider resection. RESULTS: ER were present in the gallbladder mucosa in all the
      three groups in proportions which were not significantly different (9/21 in
      carcinoma, 4/19 in gallstones, and 1/6 normal), whereas the expression of PgR was
      greater in carcinomas (13/18), less in cholelithiasis (4/12), and absent in
      normal gallbladders. PgR expression was higher in tumors of lower stage (7/7) and
      lower in advanced disease stage IV tumors (6/11). PgR expression was associated
      with better disease stage (p=0.05) and significantly longer overall survival
      (median survival of 301 d vs 54 d) as well as better survival within the same
      stage (269 d vs 54 d for stage IV disease, p=0.011). Cox's regression analysis
      showed that PgR was an independent risk factor (R=0.2283, p=0.0035). CONCLUSIONS:
      Our findings suggest that the female sex hormones may have a role in the
      pathogenesis of gallbladder cancer and that PgR expression has a prognostic
      significance. We believe that when this relationship is reaffirmed by larger
      studies, gallbladder cancer may be treated with appropriate sex hormonal
      manipulation.

PMID- 15722576
TI  - New drugs for colorectal cancer (irinotecan, oxaliplatin, raltitrexed) meet
      expectations in routine practice: a single center's experience before and after
      their introduction.
AB  - BACKGROUND AND AIMS: Treatment of metastatic colorectal cancer with new drugs
      (NDs) as oxaliplatin and irinotecan had improved response and survival. In order
      to check whether the promising achievements of the trials are obtained in routine
      clinical practice, we have reviewed retrospectively our results for two periods,
      before (period A: 1993-1995, n=63) and after (period B:1998-2000 n=103) the
      introduction of these NDs. Patients characteristics, treatment modalities,
      survival, and prognostic factors were compared. PATIENTS: There were 74 women and
      92 men, aged 60.8+/-11.6 yr, 7 patients received best supportive care only, 91
      had synchronous metastasis. RESULTS: Period B patients were older, with WHO
      score>1 more often, more adjuvant treatment, more metachronous metastasis, and
      NDs used more frequently (24% vs 59%). Median survival was similar (16 vs 15 mo).
      But when looking at the population aged<75 years with WHO score<2, median
      survival was 13 mo (period A) vs 21 mo (period B); survival at 1, 2, and 3 yr
      were respectively 59.5+/-8%, 16.2+/-6 %, 13.5+/-6 % vs 69.8+/-6%, 49.6+/-7%,
      29.8+/-7%, p<0.01). In multiparametric analysis, factors correlated with survival
      were the absence of elevated serum alkaline phosphatase, a unique metastatic
      organ, and administration of NDs. CONCLUSION: In our routine clinical experience
      the use of NDs for metastatic CRC has allowed a significant improvement in
      survival among patients with unresectable tumors.

PMID- 15722577
TI  - Pure gastric yolk sac tumor that was diagnosed after curative resection: case
      report and review of literature.
AB  - We recently experienced an 87-yr-old man with gastric yolk sac tumor.
      Preoperative diagnosis was poorly differentiated adenocarcinoma in the cardia of
      stomach without apparent metastasis. A total gastrectomy was performed. The
      precise histological examination after surgery revealed the tumor was composed of
      pure gastric yolk sac tumor without adenocarcinomatous components. The surgical
      margin and the resected lymph nodes were histologically negative for the tumor
      and a curative resection was performed. Five months after the operation,
      enlargement of the intraabdominal lymph nodes occurred with elevation of serum
      alpha fetoprotein (AFP), and the patient died 2 mo later. Gastric yolk sac tumors
      are very rare, and only six cases of gastric yolk sac tumors have been previously
      reported in the literature. Five out of six cases are accompanied by components
      of adenocarcinoma, and our present case is the second report of pure gastric yolk
      sac tumor to the best of our knowledge.

PMID- 15722578
TI  - Can large B-cell lymphoma mimic cystic lesions of the spleen?
AB  - A 58-yr-old male with a history of hepatitis C virus infection, presented with a
      2-mo history of intractable left upper abdominal pain. He had fallen from a
      ladder 2 yr previously, landing on his left side. Abdominal computed tomography
      identified a large cystic mass in the spleen. The patient was brought to the
      operating room with a presumptive diagnosis of symptomatic, post-traumatic, false
      cyst of the spleen. Instead, at surgery, a splenic mass with dense adhesions to
      the diaphragm and stomach was found. On final histological analysis, it was
      diagnosed to be a large B-cell lymphoma. Despite its rarity, gastroenterologists
      and surgeons should be aware of large B-cell lymphoma when encountering cystic
      lesions of the spleen, because the management of benign cystic disease is usually
      nonsurgical.

PMID- 15722579
TI  - Superficially spreading cholangiocarcinoma.
AB  - Cholangiocarcinoma of a raised, elevated type, not an infiltrative type, may be
      accompanied with superficial spread in the contiguous mucosa. We report a case of
      an extrahepatic cholangiocarcinoma that showed a specific cholangiographic
      finding of extensive superficial spread. The patient was a 62-yr-old man.
      Cholangiography revealed an elevated lesion in the middle of the bile duct, which
      was surrounded by irregularity of the bile duct wall extensively. We accurately
      diagnosed the tumor extent by percutaneous transhepatic cholangioscopy and
      achieved radical resection without hepatic resection. The margins were tumor
      negative by microscopy. In conclusions, it is important to accurately diagnose
      the extent of superficial spread preoperatively by cholangioscopy and biopsy, and
      decide the resecting lines to make margins tumor-negative.

PMID- 15722580
TI  - Misinterpretation of osteodensitometry with high bone density: BMD Z > or = + 2.5
      is not "normal".
AB  - Osteodensitometry is increasingly used to identify low bone density resulting
      from osteoporosis. The universally accepted World Health Organization (WHO)
      criteria for assessing bone mineral density (BMD) contrasts individual T-scores
      to peak BMD in healthy adult control populations. In this scheme, "osteoporosis"
      refers arbitrarily to T-values below -2.5, "osteopenia" to values between -1.0
      and -2.5, and "normal" to values above -1.0. Although individually rare, numerous
      conditions cause supranormal BMD in children and adults. Increasingly, elevated
      BMD is detected by osteodensitometry, especially dual-energy X-ray
      absorptiometry. Illustrated here, the absence of upper limits for BMD in the WHO
      criteria jeopardizes recognition of high-BMD disease for all age groups. This
      oversight requires correction using Z-scores.

PMID- 15722582
TI  - Effect of 99mTc-MDP administration on dual-energy X-ray absorptiometry bone
      mineral density measurements.
AB  - The effect of a diagnostic dose of (99m)Tc-MDP on bone mineral density (BMD)
      estimations in the lumbar spine and the neck of femur was assessed in 20 patients
      using a Hologic QDR4500 scanner. Each patient underwent a DXA assessment prior to
      and 1 h following injection of (99m)Tc-MDP (mean dose-910 MBq). For comparative
      purposes, the precision of BMD estimation without the presence of a radioisotope
      was assessed by performing two sequential DXA studies on 30 volunteers and was
      found to be less than 0.01 g/cm(2). No significant change in BMD reading was
      detected following (99m)Tc-MDP injection for either measurement site and the
      precision of the readings was similar to that observed for the 30 volunteers.
      This study has shown that any effect produced by a typical bone scan dose of
      (99m)Tc-MDP is small in comparison with the intrasubject variance when estimating
      BMD using a Hologic QDR4500 scanner.

PMID- 15722581
TI  - A systematic review of the effect of alendronate on bone mineral density in men.
AB  - Alendronate is known to increase bone mineral density (BMD) at the lumbar spine
      and hip in women, but less information is available in men. We conducted a
      systematic review of randomized controlled trials to determine whether oral
      alendronate improves BMD at the lumbar spine and hip in men with low bone mass or
      prevalent fractures, compared with men treated with placebo, calcium, or vitamin
      D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry)
      increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck
      in alendronate-treated patients compared to controls. The pooled estimates of
      changes in BMD with 10 mg of alendronate daily compared to controls were as
      follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the
      lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for
      treatment effect in each analysis). Statistically significant heterogeneity of
      treatment effect was noted between trials. We conclude that 10 mg of oral daily
      alendronate is significantly associated with increase in BMD at the lumbar spine
      and hip in men over 2-3 yr and that these changes are similar to those previously
      observed in postmenopausal women.

PMID- 15722584
TI  - Construction and validation of a population-based bone densitometry database.
AB  - Utilization of dual-energy X-ray absorptiometry (DXA) for the initial diagnostic
      assessment of osteoporosis and in monitoring treatment has risen dramatically in
      recent years. Population-based studies of the impact of DXA and osteoporosis
      remain challenging because of incomplete and fragmented test data that exist in
      most regions. Our aim was to create and assess completeness of a database of all
      clinical DXA services and test results for the province of Manitoba, Canada and
      to present descriptive data resulting from testing. A regionally based bone
      density program for the province of Manitoba, Canada was established in 1997.
      Subsequent DXA services were prospectively captured in a program database. This
      database was retrospectively populated with earlier DXA results dating back to
      1990 (the year that the first DXA scanner was installed) by integrating multiple
      data sources. A random chart audit was performed to assess completeness and
      accuracy of this dataset. For comparison, testing rates determined from the DXA
      database were compared with physician administrative claims data. There was a
      high level of completeness of this database (>99%) and accurate personal
      identifier information sufficient for linkage with other health care
      administrative data (>99%). This contrasted with physician billing data that were
      found to be markedly incomplete. Descriptive data provide a profile of
      individuals receiving DXA and their test results. In conclusion, the Manitoba
      bone density database has great potential as a resource for clinical and health
      policy research because it is population based with a high level of completeness
      and accuracy.

PMID- 15722583
TI  - Does a distal forearm fracture lead to evaluation for osteoporosis? A
      retrospective cohort study in 147 Danish women.
AB  - In postmenopausal women, a low-trauma distal forearm fracture is a risk factor
      for osteoporosis and future fracture, which indicates osteoporosis follow-up
      according to prevailing guidelines. We decided to determine how often women over
      45 yr presenting with a low-trauma distal forearm fracture to a Danish emergency
      department during a 1-yr period were followed up for osteoporosis. We performed a
      retrospective review of hospital records and we sent the women and their general
      practitioners (GPs) questionnaires regarding the follow-up undertaken in primary
      care. Finally, we invited the women for a densitometry to estimate the prevalence
      of osteoporosis. From May 1, 2001 to April 30, 2002, 147 women presented with a
      low-trauma distal forearm fractures. According to the review of hospital records,
      none of the women was referred for bone densitometry or spine X-rays. One woman
      had calcium and vitamin D supplementation (CVDS) prescribed and two were
      recommended to consult their GPs for osteoporosis follow-up. In primary care, 12
      women were referred for densitometry or spine X-rays, and 11 women started CVDS
      after the fracture. Women with risk factors for osteoporosis in addition to the
      forearm fracture were not more likely to be referred for densitometry or spine X
      rays (p = 0.10). The prevalence of osteoporosis was 24% among the 79 women who
      underwent densitometry. Our study demonstrates a low use of available measures to
      reduce the risk of future fracture in women with a low-trauma distal forearm
      fracture, and it emphasizes the need to decide on a local level how to provide
      osteoporosis follow-up for women with fragility fractures.

PMID- 15722585
TI  - Dual-energy x-ray absorptiometry measurements of total-body bone mineral during
      weight change.
AB  - Bone mineral measurements were made using dual-energy X-ray absorptiometry during
      a multicenter diet trial. There were five centers, two using Hologic QDR4500 fan
      beam scanners, two using Lunar Prodigy fan-beam scanners,and one using a pencil
      beam Lunar DPX. Measurements were made at 0, 2.5, and 6 mo. The mean weight loss
      was 7.9 kg, but there was a wide range. With the Lunar instruments, the total
      body bone mineral density reduced with weight loss, but with the Hologic
      scanners, it appeared to increase. This anomaly is similar to that observed
      previously with a Hologic QDR1000 pencil-beam scanner. It was shown that changes
      of fat distribution can lead to alterations in bone measurement without any real
      change in the skeleton. With all of the scanners, there was a strong correlation
      between the change in the bone mineral content and bone area, with some values of
      the latter being quite implausible. There was an associated worsening of long
      term precision compared with that derived from short-term duplicated scans, more
      marked with the Lunar scanners. It is concluded that measurement artifacts
      preclude the valid assessment of total-body bone mineral during weight change.

PMID- 15722586
TI  - Percentile distributions of bone measurements in Iowa children: the Iowa Bone
      Development Study.
AB  - Four hundred twenty-eight white children (200 boys and 228 girls) ages 4.5-6.5 yr
      had spine, hip, and whole-body bone mineral density (BMD) and bone mineral
      content (BMC) measured by dual-energy X-ray absorptiometry(DXA) as part of the
      Iowa Bone Development Study. Anthropometric measurements, including height,
      weight, and body mass index (BMI) were determined for each child at the time the
      bone measurements were made. The age- and gender-specific height percentile based
      on the 2000 CDC Growth Charts (www.cdc.gov/growthcharts/) was determined for each
      child. These percentiles were used to classify children into four groups as
      defined by the 25th, 50th,and 75th percentile cutpoints. Percentile distributions
      were determined within each height quartile group to delineate percentiles (5th,
      25th, 50th, 75th, 95th) for BMD and BMC. Gender differences in BMD and BMC were
      investigated before and after stratification into height groups. Boys had higher
      age-height-weight-adjusted means for most BMD and BMC measures except spine BMD.
      Bone measurements increased with height quartile, indicating that taller children
      have greater BMD and BMC compared to shorter children of the same age and gender.
      Within any given quartile,mean BMD and BMC measurements were similar for boys and
      girls, with the exception of hip BMD, for which values were consistently higher
      for boys (p < 0.05). In addition, whole-body BMC values were higher for boys in
      quartiles 1 and 3 (p < 0.05). These bone measures provide norms for young white
      children and serve as a reference for comparison with other racial and ethnic
      groups, as well as with childhood populations that are at risk for osteopenia
      because of chronic disease. Gender, age, and height are useful clinical
      predictors of BMD and BMC in young children.

PMID- 15722587
TI  - Evaluation of practical use of bone age assessments based on DXA-derived hand
      scans in diagnosis of skeletal status in healthy and diseased children.
AB  - The assessment of bone age is an important factor for the analysis of skeletal
      maturity, growth, and its aberrations. The classical method of bone age
      estimations is based on the recognition of changes in the radiographic appearance
      of the maturity indicators in hand-wrist radiographs by comparison with reference
      atlas. To apply bone age assessments, based on dual-energy X-ray absorptiometry
      (DXA)-derived hand scans, in the evaluation of skeletal status, 151 healthy
      children (4-18 yr old) and 61 with bone disorders (5-20 yr old) were
      investigated. All measurements were performed using Expert-XL and DPX-L
      densitometers (GE Lunar). Hand densitometry performed by the Expert-XL machine
      was used for the evaluation of bone age. Total-body measurements were performed
      using DPXL to calculate total-body bone mineral density (BMD) Z-score values as
      standard diagnostic parameters in pediatric densitometry and to verify diagnosis
      by taking into account assessed bone age. Strong correlations were found between
      BMD (g/cm2) and bone age in healthy children of both genders. We noted in several
      cases that low values of Z-scores (<-1) corresponded to delayed bone age in
      comparison to chronological age. After recalculation of BMD data according to
      bone age, a marked increase in Z-scores was noted, mainly in multihormonal
      pituitary-deficient subjects. It can be concluded that the use of hand
      densitometry in parallel with BMD measurements provide valuable information about
      skeletal maturation that leads to the improved diagnosis of skeletal status,
      especially in subjects with constitutional delay in growth.

PMID- 15722588
TI  - Fan-beam densitometry of the growing skeleton: are we measuring what we think we
      are?
AB  - Magnification error in fan-beam densitometers varies with distance from the X-ray
      source to the bone measured and might obscure bone mineral changes in the growing
      skeleton. Magnification was examined by scanning aluminum rods of different
      shapes (square, rectangular, solid round, and hollow round) at four distances
      above the X-ray source in two orientations, with rods aligned parallel (SI) and
      perpendicular (ML) to the longitudinal axis of the scanning table. Measured area
      (cm(2)) decreased linearly with distance above the X-ray source for all rods in
      the SI orientation (p < 0.005). Measured mineral content (g) decreased linearly
      with distance but only for SI round rods (p < 0.0001) and for ML hollow round
      rods (p < 0.005). Area and mineral content decreased 1.6-1.8% per centimeter
      above the source for round rods. Measured mineral density (g/cm(2)) decreased
      linearly with distance from the source only for ML hollow round rods (p < 0.005).
      Variation in area, mineral content, and mineral density measurements was 6.6
      6.9%, 6.9-7.5%, and 1.9-2.3%, respectively, for SI round rods. Magnification
      errors of this magnitude are problematic for clinical studies using fan-beam
      densitometry. Particularly in pediatric subjects, increases in soft tissue during
      normal growth could increase a bone's distance from the fan-beam source and
      result in apparent reductions in area and bone mineral content.

PMID- 15722589
TI  - Differences in estimates of change of bone accrual and body composition in
      children because of scan mode selection with the prodigy densitometer.
AB  - Girls of age 10-13 yr with Tanner stage I-III maturation status (n = 155) were
      measured using the Prodigy (GE Lunar) densitometer. Bone area (BA), bone mineral
      content (BMC), and bone mineral density (BMD) were assessed for the whole body,
      lumbar spine, and proximal femur using the Thin (T) and Standard (S) scan modes
      at years 1 and 3 of the study. The differences obtained between the T and S mode
      at year 1 were 1-2% for the lumbar spine and proximal femur and 5-11% for the
      whole body. For those girls whose default mode changed from T at year 1 to S mode
      at year 3, the estimated gain in BA, BMC, and BMD was 3.4%, 7.6%, and 3.1%
      respectively, lower than that obtained when scanning with the T mode at both
      times for the whole body. Small changes in magnitude but large intersubject
      variability were noted in BA, BMC, and BMD of the lumbar spine and proximal femur
      when scanned with the default mode of T at year 1 and S at year 3 compared to T
      or S at both years. Errors of this size are comparable to the changes expected
      with longitudinal intervention studies and are, therefore, clinically relevant.

PMID- 15722590
TI  - Distal tibia areal bone mineral density: use in detecting low aBMD of the hip in
      young women.
AB  - Dual-energy X-ray absorptiometry (DXA) is a primary clinical tool for
      identification of adults with low areal bone mineral density (aBMD) and who are
      at increased risk for future osteoporosis and fragility fractures. Procedures for
      several aBMD scans of clinical interest might be limited by artifact,
      inaccessible anatomical regions, and positioning errors. Sites for scanning that
      overcome these limitations need further investigation for application to large
      scale screening and relevance to clinical decisions regarding diagnosis and
      treatment. In this study, 146 women (mean +/- SE age = 20.1 +/- 0.1 yr, height =
      163.3 +/- 0.2 cm, weight = 60.0 +/- 0.2 kg) underwent DXA of the total body (TB)
      and right and left total proximal femurs (TPF), total forearms (TF), and distal
      tibiae (DT). Osteopenia was identified in 24 women. Areal BMD was positively
      related among all measurement sites (r = 0.55-0.81, all p < 0.001). Total body,
      TF, and DT aBMD each displayed low sensitivity (0.29-0.33) and high specificity
      (0.95-0.98) to detect osteopenia of the TPF. Addition of TB fat-free mass
      slightly enhanced the predictive value of DT aBMD. Overall, DT aBMD can
      discriminate between osteopenic and normal subjects with comparable accuracy to
      TB or TF aBMD.

PMID- 15722591
TI  - Age-related decline in bone mass measured by dual-energy X-ray absorptiometry and
      quantitative ultrasound in a population-based sample of both sexes:
      identification of useful ultrasound thresholds for osteoporosis screening.
AB  - Quantitative ultrasound (QUS) can be used as a screening tool for low bone
      mineral density (BMD), but clinical guidelines have not been set. The aim of this
      population-based, cross-sectional study was to compare age-related changes in
      bone mass measured by QUS (Lunar, Achilles Plus) and dual-energy X-ray
      absorptiometry (DXA) in a random sample of 1630 individuals (1041 females, 589
      males) 30-85 yr of age. Individuals with DXA T-scores < or =-2.5 at the femoral
      neck or total hip were identified and receiver operating curves (ROCs) were used
      to calculate cutoff points for QUS. Sensitivity, specificity, and kappa
      statistics were calculated. Age-related bone loss was significantly larger with
      QUS than DXA at all sites in women. For men, the curves were similar for QUS and
      DXA in the hip. Similar correlations were found between QUS and DXA in different
      age groups of both sexes (0.36-0.60). For women aged 50-65 yr, a QUS T-score >
      1.0 was found to be the most applicable for identifying normal BMD. In the 70-85
      yr age group, a T-score <-2.5 for women and a T-score <-0.5 for men seemed
      reasonable cutoffs for identifying normal BMD (sensitivity: 86-93%; specificity:
      28-44%; discordance: 33-73%). Calcaneal QUS cannot be used for the diagnosis of
      osteoporosis according to WHO criteria, but it can be of use to exclude
      osteoporosis in 30-40% of our cases.

PMID- 15722592
TI  - Influence of image-capturing parameters on digital X-ray radiogrammetry.
AB  - The purpose of this study was to evaluate the importance of different image
      capturing conditions, which might influence the characteristics of radiographs
      and, consequently, impact calculations of bone mineral density (BMD) and
      Metacarpal Index (MCI) using digital X-ray radiogrammetry (DXR). Radiographs of
      the left hand of deceased males were acquired three times using systematically
      varied parameters: 4-8 miliamp seconds (mA); 40-52 kV; film-focus distance (FFD);
      90-130 cm; film sensitivity, 200/400; and different image modalities
      (conventional vs original digital radiographs as well as digital printouts).
      Furthermore, the interradiograph reproducibility using both conventional
      equipment and printouts vs originals of digital images and the intraradiograph
      reproducibility (either conventional or digital printouts) were evaluated. All
      BMD and MCI measurements were obtained with the DXR technology. The
      interradiograph reproducibility of DXR-BMD using conventional images under
      standardized conditions (6 mAs; 42 kV; 1 m FFD; film sensitivity of 200) was
      calculated to be coefficient of variation (CV) = 0.49% for Agfa Curix film and CV
      = 0.33% for Kodak T-MAT-Plus film, whereas reproducibility error using digital
      images ranged from CV = 0.57% (digital printouts; Philips) to CV = 1.50%
      (original digital images; Siemens). The intraradiograph reproducibility error was
      observed to be CV = 0.13% (conventional; Kodak film) vs CV = 0.27% (digital
      printouts; Philips). The BMD calculation was not noticeably affected by changes
      of FFD, exposure level, or film sensitivity/film brand, but was influenced by
      tube voltage (CV = 0.99% for Kodak film to CV = 2.05% for Siemens digital
      printouts). No significant differences were observed between the BMD and MCI
      data. DXR provides measurements of MCI and BMD with high precision and
      reproducibility. The measurements are unaffected by all tested image-capturing
      conditions, with the exception of tube voltage. In addition, different digital
      image devices clearly have an effect on DXR reproducibility.

PMID- 15722593
TI  - Effects of bone density feedback and group education on osteoporosis knowledge
      and osteoporosis self-efficacy in premenopausal women: a randomized controlled
      trial.
AB  - In this 2-yr randomized controlled trial, we examined the effect of bone mineral
      density feedback and two different educational interventions (an osteoporosis
      information leaflet and group-based behavioral education [OPSMC]) on osteoporosis
      knowledge and self-efficacy in 470 women aged 25-44 yr. Osteoporosis knowledge
      increased across all intervention groups. Women receiving the OPSMC had a greater
      increase in both short (beta = +1.33, 95% confidence interval [CI] = 0.72-1.94)
      and long-term (beta = +0.64, 95% CI = 0.0034-1.25) osteoporosis knowledge,
      compared to those receiving the leaflet. In contrast, a low T-score was
      associated with a significant increase in long-term (beta = +0.66, 95% CI =
      0.0034-1.25) but not short-term (beta = +0.57, 95% CI = -0.036 to 1.17)
      osteoporosis knowledge, compared to a normal T-score. Changes in osteoporosis
      self-efficacy were not associated with either low bone mineral density or
      receiving the OPSMC but were negatively associated with number of children (beta
      = -0.9, 95% CI = - 1.4 to -0.3) and working more than 20 h per week (beta = -2.7,
      95% CI = -4.6 to -0.8). In conclusion, both the OPSMC and bone density feedback
      increased osteoporosis knowledge but not self-efficacy over 2 yr. Women with
      children or who worked full time have decreased osteoporosis self-efficacy,
      suggesting that this group should be a specific target for future interventional
      strategies.

PMID- 15722594
TI  - Multicenter evaluation of commercial frozen plates for microdilution broth
      antifungal susceptibility testing of yeasts and comparison of MIC limits
      recommended in NCCLS M27-A2.
AB  - A commercial kit, Frozen Plate for Antifungal Susceptibility Testing of Yeasts,
      Eiken (Eiken Chemical Co., Ltd., Tokyo), was tested in a multi-institute study to
      evaluate the agreement between interinstitute MICs and National Committee for
      Clinical Laboratory Standards (NCCLS) M27-A2 recommendation limits of MIC value.
      The kit was reported as a method equivalent to the standardized guidelines for
      antifungal susceptibility testing by the Committee for Clinical Laboratory
      Standards-1994, the Japanese Society for Medical Mycology, and which is widely
      used in Japan for amphotericin B, flucytosine, fluconazole, miconazole, and
      itraconazole. The degrees of inter-institute and NCCLS agreements were good to
      excellent especially with 48-hr incubation for all antifungal agents. However,
      the percent agreements to NCCLS recommendations against itraconazole were poor.
      Overall, MIC values obtained using the frozen plate antifungal susceptibility
      testing kit, with 48-hr incubation, were thought to be reliable and convenient
      alternatives to the data obtained by the NCCLS M27-A2 reference macrodilution and
      microdilution method. This kit will allow matching of results between
      international laboratories. However, the MIC value for itraconazole requires
      careful interpretation.

PMID- 15722595
TI  - Epidemiology of typhoid carriers among blood donors and patients with biliary,
      gastrointestinal and other related diseases.
AB  - Enteric fever due to Salmonella Typhi is a major public health problem. Typhoid
      carriers have high titres of Vi agglutinins in their sera. We worked out the
      baseline data for Vi agglutinins from 705 healthy blood donors (controls) by
      ELISA and compared it with 446 patients with biliary, gastrointestinal and other
      related diseases (cases). The samples were divided into five groups based on the
      disease condition of the patients from whom they were collected. Group A (n=196)
      consisted of patients with stones in the gall bladder/common bile duct and Group
      B (n=27) with gall bladder carcinoma. Group C (n=33) comprised patients with
      carcinoma of the pancreas/ampulla, obstructive jaundice and/or
      cholangiocarcinoma. Group D (n=112) had patients with acute/chronic pancreatitis,
      abdominal pain, intestinal obstruction, peritonitis, carcinoma oesophagus,
      chronic diarrhoea, gastrointestinal bleeding and dyspepsia. Group E (n=78)
      included patients with miscellaneous diseases. The mean absorbance value obtained
      for healthy subjects +3 standard deviations was taken as the cut-off value for a
      positive typhoid carrier. In Group A, 10.2% samples were positive; in Group B,
      7.4%; in Group C, 12.0%; in Group D, 9.8% and in Group E, 9.0%. There was a
      highly significant (P <0.001) increase in the presence of Vi agglutinins in the
      cases compared to the controls. High prevalence of typhoid carriers occurs in
      patients with biliary, gastrointestinal and other related diseases. Vi serology
      employing highly purified Vi antigen offers a practical and cost-effective way of
      screening for S. Typhi carriers.

PMID- 15722596
TI  - Nasal peptide vaccination elicits CD8 responses and reduces viral burden after
      challenge with virulent murine cytomegalovirus.
AB  - Infection of BALB/c mice with murine cytomegalovirus (MCMV) leads to CD8 cell
      responses to an immunodominant epitope YPHFMPTNL. We presented this epitope as a
      nasal peptide vaccine in combination with cholera toxin adjuvant, and evaluated
      immune responses and protection from MCMV challenge. Vaccination of naive mice
      generated elevated numbers of peptide-specific interferon-gamma-secreting
      splenocytes (median 80/million, range 60 to 490), compared to control mice
      (median 2/million, range -4.5 to 8; P=0.008, Mann-Whitney test). Twelve days
      after challenge with virulent MCMV, vaccinated mice had a 1.1 log(10) reduction
      in salivary gland viral titer compared to unvaccinated controls (5.36+/-0.24 vs.
      6.42+/-0.12, mean +/-SD log(10) plaque-forming-units; P <0.001, t -test). Mice
      with chronic MCMV infection had consistent responses to the peptide (183+/
      24/million interferon-gamma-secreting splenocytes). Nasal peptide vaccination
      during chronic infection boosted peptide-specific responses in two of four mice
      to >900/million interferon-gamma-secreting splenocytes. Nasal peptide vaccination
      was immunogenic in naive and MCMV-infected mice, and reduced viral burden in
      naive mice after virulent MCMV challenge. The nasal route may be useful for
      peptide presentation by novel human vaccines.

PMID- 15722597
TI  - Molecular epidemiology of adenovirus infection among pediatric population with
      diarrhea in Asia.
AB  - A total of 3,577 fecal specimens from infants and children with acute
      gastroenteritis in Japan, Korea and Vietnam during 1998 and 2001 were tested for
      adenovirus by the ELISA method. Of these, adenovirus was detected in 158 (4.4%).
      The detection rate of adenovirus was highest in Korea (8.7%, 20/231) followed by
      5.0% (100/1,991) in Japan and 2.8% (38/1,355) in Vietnam. All adenoviruses were
      further serotyped by PCR-RFLP. The diversity of adenovirus serotypes including
      Ad2, 3, 5, 8, 31, 40 and 41 was demonstrated. Worth of note was a decrease in the
      rate of isolation of Ad40 (7.6%, 12/158) and a concomitant increase of Ad41
      (63.9%, 101/158) to become the predominant serotype. Another interesting feature
      of the study was the presence of Ad3 (4.0% and 30%) and Ad8 (8.0% and 20%) in
      Japan and Korea, respectively, which is mainly associated with
      keratoconjunctivitis worldwide. Our result underscored the importance of
      adenovirus in association with acute gastroenteritis in Asian countries.

PMID- 15722598
TI  - Production of autoantibodies associated with polyclonal activation in Yersinia
      enterocolitica O: 8-infected mice.
AB  - Polyclonal lymphocyte stimulation is one of the immunomodulatory mechanisms
      induced by arthritogenic pathogens. In this study we examined the polyclonal
      activation potential of a virulent strain of Y. enterocolitica serotype O: 8 (WA
      2707(+)) and its plasmidless isogenic pair (WA 2707(-)). SPF Swiss mice were
      infected intragastrically and spleen cells were obtained on days 7, 14, 21, 28,
      35 and 42 after infection. The number of cells secreting nonspecific
      immunoglobulins of IgG, IgM and IgA isotypes was determined by the ELISPOT
      technique. The presence of serum-specific antibodies was investigated by ELISA
      and the presence of autoantibodies by dot-blot assay. Although the patterns of
      infection of the two bacterial strains were almost the same, only the animals
      infected with the virulent strain presented clinical anomalies. Neither arthritic
      nor inflammatory signs were observed in the joints of the infected animals. The
      greatest activation observed was that of the nonspecific IgM-secreting cells, and
      their peak of secretion occurred between the 28th and the 42nd day after
      infection, for both strains of Y. enterocolitica O: 8. Only the animals infected
      with the virulent strain (WA 2707(+)) produced IgG-specific antibodies in the
      serum, from the 28th day after infection. The serum of animals infected with
      either strain showed reactivity to all the autologous constituents tested, mainly
      on the 28th and 42nd day after infection. It was concluded that infection of mice
      with either the virulent strain of Y. enterocolitica O: 8 or with its plasmidless
      isogenic pair resulted in the polyclonal activation of the splenic B lymphocytes
      including some autoreactive clones.

PMID- 15722599
TI  - Comparison of effects of nitric oxide synthase (NOS) inhibitors on plasma
      nitrite/nitrate levels and tissue NOS activity in septic organs.
AB  - An excessive production of nitric oxide (NO) by NO synthase (NOS) is considered
      to contribute to circulatory disturbance, tissue damage, and refractory
      hypotention, which are often observed in septic disorders. It is anticipated that
      a selective inducible NOS (iNOS) inhibitor with excellent pharmacokinetics may be
      potentially effective as a novel and potent therapeutic intervention in sepsis.
      We examined whether or not a selective iNOS inhibitor shows iNOS selectivity at
      the tissue level, when administered systemically. The effects of four NOS
      inhibitors on plasma nitrite/nitrate (NOx) and tissue NOS levels were compared in
      major organs (lungs, liver, heart, kidneys, and brain) 6 hr after the injection
      of E. coli lipopolysaccharide (LPS) into male Wistar-King rats. The rats treated
      with the three iNOS inhibitors (N-(3-(aminomethyl)benzyl)acetamidine (1400W), (1
      S, 5 S, 6 R, 7 R )-2-aza-7-chloro-3-imino-5-methylbicyclo [4.1.0] heptane
      hydrochloride (ONO-1714), and aminoguanidine) administered 1 hr after LPS
      injection, showed dose-dependent decreases in plasma NOx levels and NOS activity
      in the lungs. The non-selective NOS inhibitor (N(G)-methyl-L-arginine (L-NMMA))
      had an effect only at the maximum dose. The differences in in vitro iNOS
      selectivity among these drugs did not correlate with iNOS selectivity at the
      tissue level. The relationship between plasma NOx levels and NOS activity in the
      lungs showed a linear relationship with or without the NOS inhibitors. In
      conclusion, the iNOS selectivity of these drugs does not seem to differ at the
      tissue level. Plasma NOx levels may be a useful indicator of lung NOS activity.

PMID- 15722600
TI  - Facilitated production of secretory IgA against Shiga toxin B subunits by
      intranasal application of antigen-coated polystyrene microspheres.
AB  - We examined the effects of microspheres as antigen carriers in mucosal
      immunization. Shiga toxin B subunits (Stx1B) were adsorbed on 6 mum polystyrene
      microspheres, which were then intranasally administered to mice together with
      cholera toxin (CT). Stx1B-specific serum IgG production and secretory IgA
      production at local mucosal sites were enhanced by the use of microspheres. When
      OVA was used as a model antigen, secretory IgA production but not serum IgG
      production was enhanced on the use of microspheres. These results indicated that
      microspheres provide a useful means of potentiating the immune response against
      Stx1B with weak immunogenicity.

PMID- 15722601
TI  - Interleukin-4 up-regulates T-tropic human immunodeficiency virus type 1
      transcription in primary CD4+ CD38+ T-lymphocyte subset.
AB  - The capacity of human immunodeficiency virus type 1 (HIV-1) to infect resting
      cells and to produce progeny particles may contribute significantly to its
      pathogenicity in vivo. We previously reported that primary culture of resting
      CD4(+) CD38(+) T-lymphocyte subset had higher production rate of CXCR4-using (X4)
      HIV-1 than CD4(+) CD38(-) subset. Interleukin (IL)-4 highly contributed to the up
      regulation of the X4 virus production in the CD38(+) subset. Here, we show
      evidences that IL-4 treatment of both resting CD38(+) and CD38(-) subsets allowed
      the adsorption, entry, and integration of X4 virus at similar rates, while the
      following viral transcription rate was significantly lower in the CD38(-) than
      CD38(+) subset. Treatment of the CD38 subsets with IL-4 or phytohemagglutinin
      revealed no association of X4 virus replication ability in the subsets with
      classic T-cell activation or proliferation. Interestingly, the activator protein
      (AP)-1 was significantly activated in the CD38(+) subset after IL-4 treatment,
      while both nuclear factor (NF)-kappaB and signal transducers and activator of
      transcription (STAT)-6 were activated in the IL-4-treated CD38(-) and CD38(-)
      subsets at similar levels. Thus, IL-4-dependent X4 HIV-1 transcription occurs
      efficiently in the CD38(+) but not CD38(-) subset of CD4(+) population and AP-1
      could play a significant role on viral transcription, leading to the up-regulated
      X4 virus production in the CD38(+) subset.

PMID- 15722602
TI  - Natural recombinant between equine herpesviruses 1 and 4 in the ICP4 gene.
AB  - Equine herpesvirus 1 (EHV-1) is a pathogen causing rhinopneumonia in young
      horses, abortion in mares, and myeloencephalitis in adult horses. Two types, EHV
      1 P and EHV-1 B, have recently been dominant among 16 electropherotypes. EHV-1 P
      and EHV-1 B viruses were compared by long and accurate polymerase chain reaction
      (LA-PCR) and restriction fragment length polymorphism (RFLP) analysis.
      Differences in restriction sites were found to be focused in ORF64, which encodes
      the infected cell protein 4 (ICP4), and downstream of the ICP4 gene. The 3 ' -end
      and downstream of ICP4 gene of EHV-1 B were found to be replaced by the
      corresponding region of EHV-4, indicating that EHV-1 B is a naturally occurring
      recombinant virus between progenitors of EHV-1 P and EHV-4. This is the first
      report showing a natural interspecies recombinant in alphaherpesviruses.

PMID- 15722603
TI  - Susceptibility loci to coronary arteritis in animal model of Kawasaki disease
      induced with Candida albicans -derived substances.
AB  - We have established an animal model of coronary arteritis which is
      histopathologically similar to that observed in cases of Kawasaki disease (KD),
      is a well-known childhood vasculitis syndrome. Coronary arteritis in this mouse
      model has been induced by intraperitoneal injection of Candida albicans -derived
      substances (CADS). Arteritis varied by mouse strain with the highest incidence by
      71.1% (27/38) found in C3H/HeN mice, but absent in CBA/JN mice (0%, 0/27),
      suggesting association of genomic background to develop the disease. The present
      study aims to elucidate the susceptibility loci associated with coronary
      arteritis by using this animal model. The association of the onset of arteritis
      with polymorphic microsatellite markers between the two strains was examined
      using one hundred and fifteen of N1 backcross progeny [(CBAxC3H)F1xC3H]. Based on
      our analysis, arteritis-susceptibility loci with suggestive linkage were mapped
      on D1Mit171 and D1Mit245(map position 20.2 cM) on chromosome 1 (P=0.0019). These
      loci include several kinds of inflammatory cytokine receptors, such as
      interleukin 1 receptor and tumor necrosis factor receptor. We also found the
      cytokine response against CADS, levels of inflammatory cytokines interleukin-1
      beta, tumor necrosis factor-alpha, and interleukin-6 in sera increased within 24
      hr after CADS injection. Our results may indicate based on genomics that ligand
      receptor interaction between these inflammatory cytokines and the receptors of
      these cytokines may affect the onset of arteritis.

PMID- 15722604
TI  - Effects of N-methyl-d-aspartate, glutamate, and glycine on the dorsal column
      axons of neonatal rat spinal cord: in vitro study.
AB  - The effects of N-methyl-D-aspartate (NMDA), glutamate, and glycine on the
      developmental axons of the neonatal rat spinal cord were investigated. Isolated
      dorsal column preparations from postnatal day (PN) 0 to 14 Long-Evans hooded rats
      (n = 119) were used in vitro. Compound action potentials (CAPs) were recorded
      from the cuneate and gracile fasciculi with a glass micropipette electrode. NMDA
      (100 microM) significantly increased CAP amplitude in PN 0-6 cords by 21.5 +/-
      9.2% (mean +/- standard error of the mean, p < 0.001, n = 8) and in PN 7-14 cords
      by 6.7 +/- 6.6% (p < 0.001, n = 10). NMDA (10 microM) significantly increased the
      CAP amplitude by 6.3 +/- 2.9% in PN 0-6 cords (p < 0.01, n = 10). The increase of
      CAP amplitude induced by NMDA (100 microM) in PN 0-6 cords was significantly
      greater than that in PN 7-14 cords (p < 0.005). Glutamate (100 microM)
      significantly increased the CAP amplitude by 8.8 +/- 8.1% in PN 0-6 cords (p <
      0.001, n = 29) and 6.7 +/- 7.5% in PN 7-14 cords (p < 0.01, n = 14), and
      glutamate (10 microM) significantly increased by 6.3 +/- 2.9% in PN 0-6 cords (p
      < 0.01, n = 21). The amplitudes induced by glutamate (100 microM or 10 microM)
      did not significantly differ between PN 0-6 and PN 7-14 cords. Application of
      glycine (100 microM) did not significantly alter CAP amplitudes induced by NMDA
      (100 microM or 10 microM) and glutamate (100 microM or 10 microM). D(-)-2-amino-5
      phosphonopentanoic acid (NMDA receptor antagonist) blocked the effects of NMDA
      and glutamate. These results suggest that NMDA receptor is present on afferent
      dorsal column axons and may modulate axonal excitability, especially during the
      1st week after birth.

PMID- 15722605
TI  - Combined approach for otogenic brain abscess.
AB  - Otogenic intracranial infections usually require both neurosurgical and
      otolaryngological surgery. This prospective, non-randomized study investigated
      the value of combining both surgical procedures. Thirteen patients with otogenic
      intracranial abscess were treated by mastoidectomy and abscess removal through
      the same incision between 1993 and 2002. Another 12 patients underwent abscess
      removal or mastoidectomy followed by the other procedure within 7 days. The
      clinical features of the patients were compared. Four patients died in our
      series. All four patients had Glasgow Coma Scale (GCS) scores of 7 or less. The
      preoperative GCS score was the main factor in mortality. One patient had
      recurrence after the combined approach compared to nine patients with recurrence
      after separate procedures. The surgical procedure was the main factor affecting
      the recurrence rate. The combined approach and total capsule excision of the
      abscess may reduce the risk of recurrence of otogenic intracranial abscess.

PMID- 15722606
TI  - Traumatic C6-7 subluxation associated with C-7 fracture treated with a pedicle
      screw system under navigation guidance--case report.
AB  - A 51-year-old female presented with traumatic C6-7 subluxation associated with C
      7 fracture due to an automobile accident. She underwent pedicle screw fixation at
      C-6, C-7, and T-1 for stabilization of the spinal column. A neuronavigation
      system was used to obtain accurate placement of the pedicle screws. The patient
      recovered well without further neurological compromise. Postoperative cervical
      radiography showed reasonable restoration of the vertebral column without delayed
      kyphotic deformity.

PMID- 15722607
TI  - Type I odontoid fracture--case report.
AB  - A 17-year-old man presented with sleeping tendency, tenderness of the back of the
      neck, and left upper monoplegia after a motorcycle accident. Three-dimensional
      computed tomography on the 2nd hospital day clearly revealed a type I odontoid
      fracture. His injuries were treated conservatively and he was discharged on the
      60th hospital day, with sequelae due to the cervical root avulsion injuries. Type
      I odontoid fracture is rare and may be caused by coronal distraction of the head
      and neck area.

PMID- 15722608
TI  - Occlusion of the vertebral artery secondary to dissection of the subclavian
      artery--case report.
AB  - A 34-year-old man presented with occlusion of the left vertebral artery (VA)
      secondary to dissection of the left subclavian artery manifesting as vertigo,
      nausea, vomiting, and neck pain. On admission, he was alert with left limb and
      truncal ataxia. Magnetic resonance (MR) imaging and MR angiography showed left
      cerebellar infarction and occlusion of the left VA. Conventional angiography and
      three-dimensional computed tomography (3D-CT) angiography showed stenosis with
      thrombosed pseudo-lumen of the left subclavian artery, and occlusion of the left
      VA. Presumably the idiopathic dissection of the left subclavian artery had
      reached the orifice of the left VA, and an embolism from the dissection had
      caused occlusion of the VA, leading to cerebellar infarction. After one month, he
      was discharged without severe neurological deficits. Idiopathic dissection of the
      subclavian artery is very rare. 3D-CT angiography is very useful for the
      diagnosis of arterial dissection.

PMID- 15722609
TI  - Intraoperative color Doppler sonography in the surgical treatment of
      perimedullary arteriovenous fistula--case report.
AB  - A 36-year-old female was treated for a perimedullary arteriovenous fistula (AVF)
      using intraoperative color Doppler sonography monitoring. Color Doppler
      sonography before interruption of the fistulous point clearly demonstrated an
      abnormal hyperechoic lesion. After interruption of the shunting point, the lesion
      had disappeared. Intraoperative angiography confirmed the disappearance of the
      perimedullary AVF. Intraoperative color Doppler sonography is a noninvasive,
      reliable, and cost-effective method for monitoring the effect of interruption on
      perimedullary AVF.

PMID- 15722610
TI  - Disappearance of hemifacial spasm after ventriculoperitoneal shunting in a
      patient with achondroplasia--case report.
AB  - A 15-year-old boy with achondroplasia developed right hemifacial spasm associated
      with headache, vomiting, and hearing disturbance. Computed tomography showed
      hydrocephalus. A ventriculoperitoneal shunt was placed. His hydrocephalus
      subsequently resolved, the hemifacial spasm and headache disappeared, and his
      hearing disturbance improved. The episodes of hemifacial spasm were probably
      related to a small posterior cranial fossa volume, the so-called crowding of the
      posterior fossa. Increased intracranial pressure due to hydrocephalus apparently
      contributed to further reduction in the posterior cranial fossa volume and led to
      the hemifacial spasms. In addition, his hearing disturbance may have been the
      result of dysfunction of the cochlear nerve due to the increase in intracranial
      pressure caused by hydrocephalus.

PMID- 15722611
TI  - Minute glioma identified by 3.0 Tesla magnetic resonance spectroscopy--case
      report.
AB  - A 33-year-old man presented with a minute tumor incidentally detected by magnetic
      resonance (MR) imaging screening. 1.5 Tesla MR spectroscopy indicated normal
      brain tissue whereas 3.0 Tesla MR spectroscopy indicated neoplasm. The tumor was
      completely resected. The histological diagnosis was fibrillary astrocytoma.
      Minute glioma, measuring less than 15 mm in diameter on MR imaging, can be
      completely resected, resulting in a good prognosis. 3.0 Tesla MR spectroscopy can
      establish the diagnosis in the early stage of glioma.

PMID- 15722612
TI  - Parietal lipomeningocele--case report.
AB  - A 2-month-old female infant had had a parietal mass since birth. Neuroimaging
      revealed a lipoma under the splenium of the corpus callosum that was connected to
      the subcutaneous lipoma via a bone defect in the cranium bifidum of the parietal
      region. At the age of 5 months, partial resection of only the extracranial mass
      was carried out. The histological diagnosis was lipoma. She grew up normally
      without neurological disorders during follow up for 12 years after the surgery.
      In the present case, the intracranial lipoma was associated with the cranium
      bifidum, and dysraphism was possibly involved in the pathogenesis. Resection of
      only the extracranial subcutaneous tumor can be performed for cosmetic reasons.

PMID- 15722613
TI  - Techniques for passing the PercuSurge Guardwire system through severe and
      tortuous stenotic lesions.
AB  - Distal embolism is one of the major causes of morbidity and mortality associated
      with treating stenotic lesions by endovascular procedures, such as percutaneous
      angioplasty and stenting. Many devices have been designed and used to prevent
      this complication. The PercuSurge Guardwire system is recognized as the best
      system available to prevent distal embolism during stenting. However, this system
      is sometimes hard to pass through severe stenotic, tortuous lesions because of
      the poor selectivity and support. The PercuSurge device was safely introduced
      into two cases of severe stenotic and tortuous lesions with a triple coaxial
      system and the buddy wire technique, and stenting was performed successfully.
      These techniques are very helpful for introducing and maintaining this system in
      the correct position across stenoses with unfavorable configurations.

PMID- 15722614
TI  - Secular trend of timing of puberty.
AB  - During the last decades, a secular trend of growth and timing of puberty occurred
      consisting of increased adult height and earlier onset of puberty. In The
      Netherlands although the most recent survey showed an increase of final height
      again, the timing of puberty onset appears to level off, and in boys pubertal
      onset was even slightly retarded. Different findings were reported from the
      United States, where a strong advancement of the onset of puberty was observed in
      both white and black girls, although the effect was more evident in black girls.
      Timing of puberty follows a familial pattern and therefore seems to be controlled
      by genetic factors, whereas environmental factors may influence and mediate the
      genetic regulation. Environmental factors such as nutritional status, chronic
      diseases, migration to a healthy environment, frequent infectious diseases,
      pollution and exposure to insecticides are all thought to influence the endocrine
      regulation status and therefore differentiation and development of endocrine
      organs. In this chapter, the physiologic mechanisms of puberty onset with the
      different regulatory aspects, as well as pathologic processes interfering with
      the onset of puberty will be discussed.

PMID- 15722615
TI  - Fetal nutrition and timing of puberty.
AB  - Over the last decade growing evidence has been documented on the relationship
      between intrauterine growth retardation (IUGR) and pubertal development
      indicating changes in timing and progression of puberty. These changes in
      pubertal development are part of a growing list of IUGR-related diseases, which
      includes type 2 diabetes mellitus, cardiovascular disease, short stature and
      polycystic ovary syndrome. The influence of IUGR on the mechanisms behind the
      onset of puberty is still elusive. In the absence of prospective studies on
      gonadotropin-releasing hormone pulse patterns in IUGR children, other markers of
      pubertal development such as age at menarche in girls and progression of puberty
      have been employed. We investigated pubertal development and DHEAS levels in
      children born small for gestational age (SGA) after third trimester growth
      retardation and children born appropriate for gestational age (AGA). A faster
      progression of puberty was found in girls but not in boys. DHEAS levels tended to
      be higher in SGA children than in AGA children. In animal studies using two rat
      models, growth and onset of puberty based on perinatal undernutrition were also
      investigated. In one model intrauterine growth retardation was induced by
      ligation of the uterine arteries (IUGR) at day 17 of gestation and in the other
      model postnatal food restriction (FR) was induced by increasing litter size after
      birth until weaning. In both models, the rats showed a persistent growth failure.
      Onset of puberty was defined by vaginal opening (VO) in female rats and by
      balanopreputial separation (BPS) in male rats. At onset of puberty IUGR and FR
      rats had a lower body weight compared to controls, indicating that no threshold
      for body weight is needed for the onset of puberty. In the IUGR female rats, the
      onset of puberty was delayed and in the FR female rats the onset of puberty was
      in time. In both IUGR and FR female rats VO and first cycle were uncoupled. In
      IUGR female rats, at VO, at first cycle and at the age of 6 months the ovaries
      showed a decline in number of follicles indicating that intrauterine malnutrition
      in the female rat has a permanent influence on the growth and development of
      follicles. In the FR female rats, at VO, the ovaries showed a normal number of
      follicles but an abnormal maturation pattern. At the time of first cycle and at
      the age of 6 months normalization in follicle growth pattern was observed. These
      findings suggest that postnatal undernutrition has a transient influence on
      follicle growth and development. In male rats, both models showed delayed onset
      of puberty and impaired testicular function, as shown by decreased testosterone
      levels. These data indicate that early malnutrition during different critical
      developmental time windows may result in different long-lasting effects on
      pubertal development in both humans and rats.

PMID- 15722616
TI  - Adrenal function of low-birthweight children.
AB  - During the neonatal period, increased stress due to infection or illness in low
      birthweight infants may increase the importance of adequate adrenal cortisol
      secretion. Such low-birthweight infants often have transient cortisol
      insufficiency during the first few days of life, but then soon develop restored
      or even high cortisol levels. The pressure to enhance survival during this
      critical period could lead to either the programming of higher cortisol
      secretion, or the favorable selection of infants who are genetically predisposed
      to produce sufficient cortisol levels and activity. However, in long-term
      survivors of low birthweight, the maintenance of higher levels of cortisol
      secretion or action may contribute to increased hypertension and cardiovascular
      disease risk in later life. Similarly, low birthweight and subsequent rapid
      postnatal weight gain are associated with increased androgen secretion from the
      adrenal zona reticularis and this may contribute to disorders of hyperandrogenism
      and hyperinsulinemia before and after puberty. Precocious pubarche, the clinical
      manifestation of adrenal hyperandrogenism prepuberty, in girls is predictive of
      polycystic ovary syndrome, and is also associated with dyslipidemia, and
      increased central fat. In conclusion, long term consequences of low birthweight
      on both adrenal cortisol and adrenal androgen secretion could contribute to
      increased risks for the metabolic syndrome in later life.

PMID- 15722617
TI  - Puberty and fertility in congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is a disorder of adrenal steroid synthesis.
      The symptoms and signs of CAH depend on the degree of enzyme deficiency; severe
      salt-wasting (SW) form, less severe simple virilizing (SV) form and mild
      nonclassic (NC) form. In this paper, puberty and fertility in CAH are discussed.
      The time of onset of puberty and progress of pubertal development is quite
      normal, except in NC patients (earlier). Also the age of menarche in CAH girls is
      normal, but it can depend on the level of therapeutic control. In prepuberty,
      bone age is advanced. In puberty, peak height velocity is normal but occurs at a
      younger age and can therefore be considered to be low (compared to healthy early
      maturers). In puberty there seems to be an increased sensitivity for
      glucocorticoids leading to growth inhibition. All three above factors can play a
      role in reducing adult height. Subfertility is frequently found in both female
      and male CAH patients. In females, the pregnancy rate depends on the severity of
      21-hydroxylase deficiency (SW<SV<NC). Adrenal progestagens and androgens are the
      main cause of disturbed ovarian activity. In addition psychosexual problems (e.g.
      as a result of genital surgery) are an important factor. In males, the main cause
      of subfertiltiy is the presence of testicular adrenal rest tumors, which are
      thought to originate from aberrant adrenal tissue and respond to treatment with
      glucocorticoids. Although in general fertility is not a paediatric item, in CAH
      most fertility problems have their origins in childhood years. Therefore
      prevention of subfertility has to be implemented as a treatment goal in
      paediatric endocrinology from the start of puberty.

PMID- 15722618
TI  - Molecular genetics of isolated hypogonadotropic hypogonadism and Kallmann
      syndrome.
AB  - Isolated hypogonadotropic hypogonadism (IHH) is characterized by complete or
      partial failure of pubertal development due to impaired secretion of luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH). In the molecular
      pathogenesis of IHH, the gonadotropin-releasing hormone receptor (GnRH-R) and
      associated proteins have evolved as a central element. GnRH-R germline mutations
      were among the first genetic alterations identified in patients with IHH. These
      mutations are associated with impaired GnRH binding, ligand-induced signal
      transduction, or both, leading to various degrees of LH and FSH deficiency. As
      GnRH-R mutations explain several but not all cases of IHH, the search for new
      candidate genes continued in informative families. In 2003, mutations of the KiSS
      1-derived peptide receptor GPR54 were identified in patients with IHH, opening a
      new pathway in the physiologic regulation of puberty and reproduction. GPR54 is
      putatively involved in the control of GnRH secretion. IHH associated with
      impaired olfactory function (Kallmann syndrome) may be caused by mutations of the
      X-chromosomal KAL1 (encoding anosmin) or the fibroblast growth factor receptor 1
      genes (FGFR1), both leading to agenesis of olfactory and GnRH-secreting neurons.
      In addition to their clinical and diagnostic value, the identification of genetic
      and functional alterations in IHH helps to unravel the complex regulation of the
      gonadotropic axis.

PMID- 15722619
TI  - Hypothalamic hamartoma: a paradigm/model for studying the onset of puberty.
AB  - This article discusses the potential mechanisms by which hypothalamic hamartomas
      (HHs) are formed and cause precocious puberty. The hypothesis is presented
      suggesting that HHs accelerate sexual development by producing bioactive
      substances that mimic - in an accelerated time-course - the cascade of events
      underlying the normal initiation of puberty. It is also proposed that because HHs
      contain key transcriptional and signaling networks required to initiate and
      sustain a pubertal mode of gonadotropin-releasing hormone (GnRH) release, they
      are able to trigger the pubertal process at an earlier age. The cellular
      components of this activating complex may include: (a) neurons able to produce
      GnRH within the HH: (b) controlling neurons synaptically connected to GnRH
      neurons in the HH itself and/or to neuronal networks (including GnRH neurons) in
      the patient's hypothalamus, and (c) signaling-competent astrocytic and
      ependymoglial cells. It is also possible that the developmental abnormalities
      leading to the formation of HHs result from sporadic defects affecting the same
      genes and hence the same morphogenic pathways involved in the embryonic
      development of the ventral hypothalamus and the floor of the third ventricle.

PMID- 15722620
TI  - Gonadotropin-releasing hormone analogue treatment for precocious puberty. Twenty
      years of experience.
AB  - Central precocious puberty (CPP) is the premature onset of puberty due to a
      precocious activation of gonadotropin-releasing hormone (GnRH) neurons in the
      hypothalamus. This condition results in accelerated development of secondary sex
      characteristics, accelerated bone maturation, impaired final height with
      disproportioned body appearance and can have a disturbing impact on the
      psychosocial behavior of children suffering from CPP. It is therefore necessary
      to assess the hormonal status of children who show pubertal signs before the age
      8 years in girls and 9 years in boys. The indication for treatment should be made
      after evaluating pubertal progression, progression of bone age maturation and
      final height prognosis, development of reproductive function, and psychosocial
      adjustment and well-being. This paper summarizes the experience of GnRH agonist
      treatment, which is momentarily the treatment of choice for central precocious
      puberty in children.

PMID- 15722622
TI  - Polycystic ovary syndrome in adolescence. New insights in pathophysiology and
      treatment.
AB  - Polycystic ovary syndrome (PCOS) is a prevalent cause of menstrual disorders,
      acne and hirsutism presenting during adolescence. In the majority of cases, a
      familial trait is obvious but the offending genes have yet to be identified.
      However, much of the pathophysiology of the syndrome causing the overproduction
      of ovarian androgens is now becoming clearer. The early diagnostic signs are
      often mistakenly dismissed as normal changes of adolescence but it is important
      to make an early diagnosis in order to save the adolescent from the early and
      late stigmata of the syndrome. The avoidance of overweight, frank obesity and the
      consequential exaggeration of symptoms by the associated insulin resistance is of
      prime importance as hyperinsulinemia plays a key role in the pathogenesis. Anti
      androgens are the most widely used medication and, in combination with estrogen,
      are capable of restoring menstrual regularity and reducing the symptoms of acne
      and hirsutism, so important for the improvement of the disturbing psychosocial
      effect that they may play at this age. The use of metformin, an insulin
      sensitizer, for affected adolescents is the topic of a presently heated debate.

PMID- 15722621
TI  - Very long-term follow-up of girls with early and late menarche.
AB  - Short- and long-term psychosocial effects of precocious or early normal puberty
      are probably more important for individuals than the moderate losses in final
      height they experience. Despite this, pediatric endocrinologists have focused
      much more on final height than psychosocial outcomes. As a surrogate for long
      term follow-up studies of girls with precocious puberty, we have reviewed the
      results of a very long-term study of physical and psychosocial development of
      girls with normal early puberty. Results revealed that at age 15-16, girls with
      menarche before age 11 (early) were more norm-breaking, including being
      delinquents. In addition, they had earlier advanced sexual experiences. By adult
      age, there were no differences in psychosocial adjustment between the early- and
      late-developed women. Thus, the effects of early pubertal timing for psychosocial
      problems seem to be adolescent-limited. At ages 27 and 43, early-developed women
      had lower academic education. Regarding somatic development, at age 43, women
      with early menarche were shorter and heavier, had worse physical fitness and
      dieted more frequently compared to other women. There was no difference in
      quality of life. In searching for reasons for the antisocial behaviors in
      adolescence and the lower educational levels among early developers, early
      heterosexual relations seem to be the most crucial.

PMID- 15722623
TI  - Reversing sex steroid deficiency and optimizing skeletal development in the
      adolescent with gonadal failure.
AB  - During puberty, the acquisition of skeletal mass and areal bone mineral density
      (BMD) mainly reflects an increase in bone size (length and perimeters) and not
      true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also
      explained by differences in bone size (longer and wider bones in males) and not
      by differences in volumetric BMD. Androgens stimulate skeletal growth by
      activation of the androgen receptor, whereas estrogens (following aromatization
      of androgens and stimulation of estrogen receptors) have a biphasic effect on
      skeletal growth during puberty. Recent evidence from clinical cases has shown
      that many of the growth-promoting effects of the sex steroids are mediated
      through estrogens rather than androgens. In addition, skeletal maturation and
      epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless,
      independent actions of androgens in these processes also occur. Both sex steroids
      maintain volumetric BMD during puberty. Androgens interact with the growth
      hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a
      sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and
      hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone
      size but also maintenance of volumetric BMD, hereby severely reducing peak areal
      BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone
      length and size, reducing areal BMD. Whether volumetric BMD is also reduced and
      whether fracture risk is increased in these conditions remains controversial.
      Replacing sex steroids according to a biphasic pattern (starting at low doses and
      ending at high-normal doses) seems the safest approach to reach targeted height
      and to optimize bone development.

PMID- 15722624
TI  - Present and future options for the preservation of fertility in female
      adolescents with cancer.
AB  - Fertility and sexuality are important aspects in the quality of life of long-term
      survivors of cancer. Adolescents in particular are in a very vulnerable period of
      their lives with respect to future fertility and sexuality. Special attention
      should be paid to preserve their fertility whenever possible. The gonadotoxic
      effect of chemotherapy is largely drug- and dosedependent and is related to age.
      The effect of radiotherapy is also dependent on dose and age and on the radiation
      therapy field. The prepubertal ovary is the least susceptible to gonadotoxicity.
      Ablative regimens for stem cell transplantation have an extremely high risk of
      ovarian failure. Alternative chemotherapy protocols can reduce long-term
      gonadotoxicity. Alkylating agents impose the highest risk in causing ovarian
      failure and should be avoided whenever possible. Up to now, the results of
      gonadoprotective hormonal therapy have been disappointing and contradictory.
      Transposition of the ovaries should be considered in each case of planned pelvic
      or whole body irradiation, where ovarian involvement is unlikely and chemotherapy
      not necessary. Cryopreservation of preimplantation embryos will seldom be
      possible in female adolescents due to the lack of a stable relationship with a
      male partner. Cryopreservation of mature and immature oocytes (necessitating in
      vitro maturation) is still assumed not to be safe for the offspring.
      Cryopreservation and transplantation of ovarian tissue seems to be the most
      promising way of future fertility preservation in female adolescents. At present,
      it is in its early experimental stage. Its safety and possibilities for fertility
      preservation in humans are not proven as yet. Additionally, technical and ethical
      issues need to be addressed. The counseling of female adolescents who are facing
      the threat of cancer needs careful consideration with regards to the psychosocial
      impact of the treatment and its consequences. Special attention should be paid to
      aspects of future quality of life, in particular: fertility and sexuality.

PMID- 15722625
TI  - Fetal growth velocities in Hong Kong Chinese infants.
AB  - Few studies have investigated the velocities of fetal growth. The aim of the
      present study was to determine the pattern of 'fetal' growth velocities in a
      Chinese population. The gestation-specific measurements of the body weight, body
      length and head circumference in a representative sample of 5,045 male and 4,484
      female newborns delivered between 26 and 42 weeks of gestation at 12 hospitals in
      Hong Kong were obtained. Peak growth velocity occurred before 30 weeks of
      gestation for head circumference, at week 30 for length and at week 30 for
      weight. When compared with data obtained from a French population, a significant
      difference in the growth velocity for body weight was observed below 32 weeks
      between French and Chinese infants, suggesting an ethnic difference in fetal
      growth of this parameter.

PMID- 15722626
TI  - Pharmacokinetics of the antineoplastic drug mitomycin C in regional chemotherapy
      using the aortic stop flow technique in advanced pancreatic carcinoma.
AB  - BACKGROUND: An isolated perfusion may lead to a higher concentration of
      cytostatics within the target tissue, which can be associated with a high
      response rate and longer survival in addition to a low rate of side effects in
      comparison with systemic palliative chemotherapy. The aim of the present study
      was to investigate the pharmacokinetics of mitomycin C utilizing the aortic stop
      flow technique with commercially available tools in patients with advanced
      pancreatic carcinoma. METHODS: Seventeen patients with unresectable or
      metastasized pancreatic carcinoma (diagnosed by histological investigation)
      underwent a 20-min hypoxic perfusion of the isolated abdominal compartment with
      20 mg/m2 mitomycin C (Mitomedac, medac, Hamburg, Germany) 22 times. Cytostatic
      concentration was determined intrainterventionally within the systemic and
      regional compartment. RESULTS: The mitomycin C concentration was 10 times higher
      within the regional compared with the systemic compartment at its maximum. The
      area under the curve was 4.02 times greater. Toxicity was considerable, i.e. WHO
      grade I/II in 8 of 17 cases, and III/IV in 9 of 17 cases. Two treatment-related
      deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1
      complete remission, 2 partial remissions). In 3 subjects, stable disease was
      registered, and in 11 individuals, tumor progression. The median survival was 4.1
      months. CONCLUSION: Though high concentrations of the cytostatic drug were
      achieved within the regional compartment, the aortic stop flow technique was
      associated with a high toxicity rate but no improvement of tumor response and
      survival in comparison with systemic chemotherapy. Despite its pharmacokinetic
      advantages, the aortic stop flow technique is currently not recommendable for
      routine use.

PMID- 15722627
TI  - Antimicrobial resistance and beta-lactamase production of clinical isolates of
      prevotella and porphyromonas species.
AB  - BACKGROUND: This study determined the beta-lactamase production and the
      antimicrobial resistance of 72 Prevotella species and 48 Porphyromonas species
      isolated from different clinical specimens. METHODS: All strains were identified
      using API 32 ID. The beta-lactamase production was determined by nitrocefin
      disks. E test strips of benzylpenicillin, ampicillin + sulbactam, cefoxitin,
      clindamycin, metronidazole and imipenem were tested for each strain. RESULTS:
      Nineteen Prevotella melaninogenica, 18 Prevotella intermedia, 16 Prevotella
      denticola, 11 Prevotella loescheii and 8 Prevotella bivia strains were
      identified. Four were clindamycin resistant. The highest beta-lactamase
      production was found at a rate of 68.4% in P. melaninogenica species.
      Additionally, 33 Porphyromonas asaccharolytica and 15 Porphyromonas gingivalis
      strains were identified. None of them produced beta-lactamase. CONCLUSION: In
      view of the emerging antibiotic resistance among anaerobes, the current local
      susceptibility profile of our Prevotella and Porphyromonas species will establish
      the basis for additional surveys tracing significant changes in the antimicrobial
      resistance of our clinical isolates.

PMID- 15722628
TI  - Laparoscopic-assisted intraperitoneal chemotherapy for patients with scirrhous
      gastric cancer.
AB  - BACKGROUND: The prognosis for patients with scirrhous gastric cancer (SGC) is
      extremely poor. To improve the patients' prognosis, laparoscopic-assisted
      intraperitoneal chemotherapy (IPC) was introduced for SGC. In this study, we
      analyzed whether IPC reduced the number of cancer cells in the peritoneal cavity
      of patients or changed the gene expression levels of cytokines in the peritoneal
      cavity. We also investigated whether IPC improved the prognosis of patients with
      SGC. METHODS: Total RNA was extracted from 50 ml of peritoneal wash from 11 SGC
      patients before and after cisplatin-based IPC. The gene expression levels of
      survivin, c-myc, transforming growth factor-beta (TGF-beta), interleukin-2 (IL
      2), IL-6, and IL-12 were analyzed using real-time reverse transcription
      polymerase chain reaction (RT-PCR) assays. Also, carcinoembrionic antigen (CEA)
      messenger RNA (mRNA) was used to identify the number of gastric cancer cells in
      peritoneal washes by the real-time RT-PCR method. The gene expression levels of
      cytokines and the number of cancer cells in the peritoneal cavity were compared
      before and after cisplatin-based IPC treatment. RESULTS: Before IPC, the gene
      expression of IL-2 from peritoneal washes of patients was significantly
      suppressed compared to the controls (p = 0.029); however, other gene expression
      levels did not differ. In 7 cases, more than 90% of the cancer cells were removed
      from the peritoneal cavity after cisplatin-based IPC. These 7 cases were named
      the IPC effective group, and the remaining 4 cases were named the IPC ineffective
      group. In the IPC effective group, elevated IL-2 and IL-6 genes were detected in
      5 (71%) and in 6 (86%) after IPC. The correlation between IPC effectiveness and
      elevated gene expression after IPC (IL-2: p = 0.137, and IL-6: p = 0.044) was
      observed. However, the 50% survival period of the IPC effective group (9 months)
      was not different from that of that of the IPC ineffective group (6 months, p =
      0.267). CONCLUSION: IPC effectiveness may correlate with elevation of gene
      expression of inflammatory cytokines, such as IL-2 and IL-6 in the peritoneal
      cavity after IPC. However, the prognostic benefits of IPC for SGC patients remain
      unclear.

PMID- 15722629
TI  - Trichophyton rubrum isolated from aids and human immunodeficiency virus-infected
      patients in Sao Paulo, Brazil: antifungal susceptibility and extracellular enzyme
      production.
AB  - BACKGROUND: In order to identify intraspecific variations in Trichophyton rubrum
      and to correlate them to the immunological status of the host, sixty strains
      isolated from AIDS, HIV-positive and HIV-negative patients were compared for the
      production of extracellular enzymes and for their susceptibility to several
      antifungal drugs. METHODS: The isolates were tested for their ability to secrete
      keratinases, proteinases, phospholipases, lipases and DNases. Likewise, we
      investigated their susceptibility to amphotericin B, ketoconazole,
      ciclopiroxolamine, griseofulvin, miconazole and tolnaftate. RESULTS: Variations
      in the Minimal Inhibitory Concentration (MIC80)) values were observed for all
      antifungals tested, but they were similarly distributed among the three clinical
      groups. Griseofulvin showed the most prominent differences among the three groups
      of isolates. Regarding enzyme secretion, all samples secreted keratinases and
      DNases, while none secreted phospholipases. Proteinases and lipases were secreted
      by some of them. CONCLUSIONS: The differences among isolates of the three groups
      were not statistically significant and therefore could not be ascribed to a given
      clinical status. Intraspecific variations similarly occurred in each group,
      irrespective of the immunological status of the patients.

PMID- 15722630
TI  - The effect of the doxycycline-rifampicin and levamisole combination on lymphocyte
      subgroups and functions of phagocytic cells in patients with chronic brucellosis.
AB  - BACKGROUND: Brucellosis is one of the important health problems for both humans
      and animals in Turkey since agriculture and stock raising appears to be the most
      important means of subsistence. Investigations on the pathogenesis of brucellosis
      reveal that the etiologic agent can survive in phagocytic cells, and cell
      mediated immunity plays an important role in immunity against bacteria. METHODS:
      In this study, we investigated whether supplementation of levamisole, a well
      known antihelminthic agent with immune-stimulating activity to conventional
      antibiotic therapy, would improve the anergy against Brucella. RESULTS: The
      results of our study reveal that a 6-week course of levamisole as a supplement to
      conventional antibiotic therapy in chronic brucellosis is not superior to
      conventional antibiotic treatment alone with respect to lymphocyte subgroup
      ratios and phagocytic function. CONCLUSION: In chronic brucellosis, levamisole
      administered as a supplement concomitantly with conventional antibiotic therapy
      has no immunostimulating effect on the basis of the lymphocyte subgroups ratios
      measured and the ability of phagocytosis in the present study. Further large
      clinical and laboratory trials are necessary to investigate the immunological and
      physiological effects of levamisole on T(H1) subtypes and cytokine secretion.

PMID- 15722631
TI  - Variation in outcomes after percutaneous coronary intervention in the United
      States and predictors of periprocedural mortality.
AB  - The objective of this study was to characterize variation in mortality rates
      across hospitals performing percutaneous coronary intervention (PCI) in the
      United States. For this purpose, data (n = 735,022) from the Nationwide Inpatient
      Sample from 1996 to 2001 were analyzed. The primary outcome for the analysis was
      postprocedural in-hospital mortality. Mortality rates were calculated by race,
      gender, geographic region, comorbid status and hospital volume. There were
      significant variations in mortality across gender groups, comorbid status,
      regions and by hospital volume status. Independent predictors of mortality in
      this large cohort were older age, female gender, lower income and lower hospital
      volume. The data suggests targets for quality improvement initiatives for
      patients undergoing PCI particularly in the elderly, females, lower income
      patients and low volume hospitals. Even in the contemporary era of adjunctive
      pharmacological therapies and ubiquitous use of stents, hospital volume remains a
      significant independent predictor of in-hospital mortality.

PMID- 15722632
TI  - Preimplantation genetic diagnosis: the earliest form of prenatal diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) can provide genetic information on
      embryos obtained through in vitro fertilization (IVF), allowing implantation of
      embryos identified as unaffected with a given genetic or chromosomal disorder.
      With the availability of increasingly sophisticated genetic testing, its use has
      advanced from the selection of female embryos for the prevention of X-linked
      genetic diseases to testing for single gene disorders via PCR. Recently, PGD has
      also been used in the setting of assisted reproductive technology to select for
      chromosomally normal embryos in an effort to increase the rates of implantation
      and successful pregnancy. As the number of patients undergoing IVF increases, the
      indications for its use broadens, and more mutations underlying genetic disorders
      are identified, PGD is becoming more widespread. As this evolution continues,
      recognition of the limitations of PGD, as well as ethical concerns regarding use
      and misuse of this technology, need to be considered by patients, clinicians, and
      policy makers.

PMID- 15722633
TI  - Characterization of wild-type recombinant Bet v 1a as a candidate vaccine against
      birch pollen allergy.
AB  - BACKGROUND: We describe the production in Escherichia coli as a recombinant
      protein of clinical grade wild-type Bet v 1a (rBet v 1a), to be used as a
      candidate vaccine against birch pollen allergy. METHODS: This recombinant protein
      was purified by hydrophobic interaction and ion exchange chromatography and
      characterized by SDS-PAGE, immunoprint and circular dichroism in parallel with
      natural Bet v 1 (nBet v 1) purified from a birch pollen extract. We also compared
      rBet v 1 and nBet v 1 for their capacity to induce histamine release from
      basophils and to stimulate T lymphocyte proliferation. RESULTS: rBet v 1a appears
      in SDS-PAGE as an 18-kDa monomeric protein, whereas purified nBet v 1 comprises a
      mixture of isoforms (resolving as three distinct bands and six spots after 1
      dimensional and 2-dimensional electrophoresis, respectively). Both recombinant
      and natural purified Bet v 1 molecules are recognized by IgE from birch pollen
      allergic patients as well as anti-Bet v 1 murine monoclonal antibodies,
      suggesting that the recombinant protein is correctly folded in a native
      configuration. Circular dichroism analysis confirmed that the two Bet v 1
      molecules exhibit similar 3-dimensional structures, even if rBet v 1a appears
      more compact and stable in thermodenaturation/renaturation experiments. Both rBet
      v 1 and nBet v 1 induce the degranulation of sensitized basophils and
      proliferation of Bet v 1-specific T lymphocytes in a similar manner. CONCLUSIONS:
      On the basis of these structural and biological properties, rBet v 1a is a valid
      candidate vaccine against birch pollen allergy, currently evaluated in humans.

PMID- 15722634
TI  - Effect of maternal dietary cow's milk on the immune response to beta
      lactoglobulin in the offspring: a four-generation study in mice.
AB  - BACKGROUND: Evaluation of immune responses to food proteins in animal models
      requires that the animals are not already sensitized or orally tolerized against
      the proteins in question. Since maternal transfer of specific immune responses
      has been observed, breeding of animals on an antigen-free diet for several
      generations may be necessary to obtain immunologically naive animals. METHODS: To
      determine the most appropriate breeding conditions of mice to be used in
      immunological studies on food proteins, we examined immune responses towards beta
      lactoglobulin (BLG) in mice bred on a milk-containing diet (F0) and then for
      three generations (F1-F3) on a commercially available milk-free diet. The
      specific antibody and cell-proliferative response to BLG was compared in non
      immunized and immunized BALB/c mice, and in mice orally tolerized to BLG prior to
      immunization. RESULTS: The immune response to BLG in the F1 generation deviated
      from the response observed in the F0 and F2/F3 generations. Importantly, trace
      amounts of BLG detected in the commercial milk-free diet did not induce oral
      tolerance. CONCLUSIONS: The study showed that breeding mice on an antigen-free
      diet for at least two generations is required to attain animals appropriate for
      immunological studies of food proteins. Although the small quantity of BLG in the
      milk-free diet did not induce detectable oral tolerance in the present study, it
      is strongly recommended that the potential effect of contaminating dietary
      antigen is considered in future studies on food proteins.

PMID- 15722635
TI  - A new immunomodulatory function of low-viscous konjac glucomannan with a small
      particle size: its oral intake suppresses spontaneously occurring dermatitis in
      NC/Nga mice.
AB  - BACKGROUND: Konjac glucomannan (GM) is a well-known dietary fiber with various
      beneficial functions: the higher viscosity displayed the stronger potency.
      However, the high-viscous GM powders, ordinary konjac powder and highly purified
      GM were mostly unsuitable for the application to various food industries. Our
      aims are to develop new physiological functions of low-viscous GM powder,
      pulverized GM or re-granulated fine GM, using a murine model of atopic
      dermatitis. METHODS: Male 4-week-old NC/Nga mice were fed for 8 weeks on diets
      containing 5% of two high-viscous and two low-viscous GM powders, respectively.
      RESULTS: Striking suppression against the aggravation of dermatitis, the increase
      in scratching behaviors, and the rise in IgE levels was recognized only in mice
      fed on the pulverized GM diet, but not in mice fed on the other GM diets or a
      control diet. Eczema prevention in the fine GM-fed mice was accompanied by a
      significant decrease in their plasma IFN-gamma levels, a positive regulatory
      cytokine for atopic skin inflammation. CONCLUSION: Only the pulverized GM
      possessed the ability to suppress the development of dermatitis in NC/Nga mice.
      This is the new immunomodulatory function of low-viscous GM with a small particle
      size.

PMID- 15722636
TI  - Nasal eosinophils display the best correlation with symptoms, pulmonary function
      and inflammation in allergic rhinitis.
AB  - BACKGROUND: The pathogenesis of allergic rhinitis and its link with asthma are
      well known. Nevertheless, a complete cross-sectional evaluation of the usually
      available clinical, functional and immunological parameters has never been made.
      We assessed nasal symptoms and flow, cytology, cytokines, pulmonary function and
      methacholine positivity in a large number of patients with pure pollinosis.
      METHODS: Young men presenting at a military hospital for routine follow-up were
      recruited for the study. They had to suffer from rhinitis alone (without asthma)
      for at least 2 years and had to have a positive skin prick test to pollens only.
      During the pollen season, they underwent symptom evaluation, measurement of nasal
      flow, nasal scraping and lavage (cell count and assay for IL-4, IL-5, IL-8 and
      IFNgamma), pulmonary function tests and methacholine challenge. RESULTS: Fifty
      subjects (23.7+/-4.9 years old) were enrolled. All patients had high clinical
      scores (9.5+/-1.6) and inflammatory cells (eosinophils: 10.5+/-4 and neutrophils
      21.3+/-6) and low nasal flow (482+/-111 ml/s). We found that the number of
      eosinophils in nasal scrapings highly correlated with all the above-mentioned
      parameters, including nasal flow, cytokines and spirometric values. A significant
      positive correlation was found between all inflammatory cells and all cytokines.
      IL-8, IL-4 and neutrophils displayed only a partial correlation with pulmonary
      parameters (FEV1, FVC and FEF25-75%), at variance wit IL-5 and eosinophils.
      Methacholine test positivity significantly correlated with the number of
      eosinophils in the nasal smear. CONCLUSION: Eosinophils in the nasal smear
      display the best correlation with all the clinical and immunological parameters
      in allergic rhinitis and also correlate well with methacholine response.

PMID- 15722637
TI  - Indolent systemic mastocytosis with elevated serum tryptase, absence of skin
      lesions, and recurrent severe anaphylactoid episodes.
AB  - BACKGROUND: In contrast to aggressive mastocytosis, patients with indolent
      systemic mastocytosis (ISM) usually present with urticaria pigmentosa-like skin
      lesions. In those who lack skin lesions, mastocytosis is often overlooked or
      confused with endocrinologic, allergic, or other internal disorders. CASE REPORT
      AND RESULTS: We report on a 33-year-old male patient in whom severe hypotensive
      episodes occurred after contact with ants or yellow jackets. Since no specific
      IgE was detected, the serum tryptase concentration was measured and found to be
      clearly elevated (70 ng/ml). Consecutive staging and examination of the bone
      marrow revealed ISM. The patient was advised to circumvent insect contact, to
      take antihistamines on demand, and to carry an epinephrine self-injector for
      emergency events. In a retrospective analysis of 40 patients seen between 1988
      and 2003, only 2 had a life-threatening mediator-related episode before ISM was
      diagnosed. CONCLUSIONS: Our report confirms the diagnostic value of tryptase in
      patients with suspected mastocytosis. In addition, the report suggests that the
      lack of typical skin lesions does not exclude an indolent form of mastocytosis
      even if the serum tryptase is clearly elevated. Finally, our case further shows
      that mastocytosis can be an important differential diagnosis to be considered in
      patients with unexplained anaphylactoid or other mediator-related symptoms.

PMID- 15722638
TI  - Quality of life during pollen season in patients with seasonal allergic rhinitis
      with or without asthma.
AB  - OBJECTIVES: We studied the evolution of generic and rhinoconjunctivitis-specific
      quality of life (QOL) during pollen season in patients with isolated seasonal
      allergic rhinitis (SAR) and those with asthma and concomitant SAR (AS+SAR).
      Generic QOL between groups was also compared at pollen peak. METHODS: A
      prospective cohort study was conducted in Southern France in 2002. Outpatients
      aged 18-60, regularly visiting respiratory physicians for SAR, were recruited
      before the grass (grass cohort) or ragweed pollination period (ragweed cohort).
      Before the pollination period (baseline) and at peak pollination, patients
      completed French versions of the Mini Rhinoconjuctivitis Quality of Life
      Questionnaire (Mini-RQLQ) and physical and mental Short Form-12 (SF-12) scores
      (PCS and MCS) to determine rhinoconjunctivitis and generic QOL. RESULTS: Totals
      of 83 and 52 patients were included in the SAR and AS+SAR groups, respectively
      (mean age=35.4; 56.4% females). Mini-RQLQ scores indicated slightly worse QOL in
      the A+SAR group at inclusion, which significantly deteriorated at the time of
      pollen peak, both in the SAR (p<0.0001) and AS+SAR groups (p=0.003). In
      univariate analysis, significantly higher SF-12 PCS (meaning better QOL) were
      observed at pollen peak in the SAR compared with the AS+SAR group (p=0.0008),
      while the difference for SF-12 MCS was more limited (p=0.05). Results were
      confirmed in multivariable analyses adjusting for gender, allergy medication use
      at pollen peak, cohort of inclusion (grass/ragweed) and comorbid conditions.
      CONCLUSIONS: Significant deterioration in rhinoconjunctivitis-specific QOL was
      observed through the pollination period in patients with SAR and AS+SAR. At
      pollen peak, AS+SAR patients experienced significantly worse physical functioning
      than patients with SAR alone.

PMID- 15722639
TI  - Impact of sublingual immunotherapy on specific antibody levels in asthmatic
      children allergic to house dust mites.
AB  - OBJECTIVE: To evaluate the clinical outcome and changes in allergen-specific
      antibodies during sublingual immunotherapy (SLIT) in house dust mite (HDM)
      allergic asthma patients and to compare levels of allergen-specific antibodies in
      HDM-allergic patients before and after treatment with that of healthy controls.
      METHOD: Thirty-one asthma patients allergic to HDM were studied. Patients in
      groups I (n=17) and II (n=14) received SLIT with a standardized Dermatophagoides
      pteronyssinus plus Dermatophagoides farinae 50/50 extract for 6 and 12 months,
      respectively. A group of healthy children (n=8) were enrolled as controls.
      Patients in both groups were evaluated at the start and at the end of treatment
      according to daily symptom and medication scores, lung function and skin prick
      tests, PC20, blood eosinophil count, and Der-p-1-specific IgE, IgA, IgG1 and IgG4
      levels. RESULTS: Drug consumption decreased significantly in both groups.
      Furthermore, PC20 and forced expiratory flow between 25 and 75% of vital capacity
      of patients in group II improved significantly. Although specific IgA, IgG1 and
      IgG4 levels did not change throughout the treatment period, total eosinophil
      count and specific IgE decreased significantly in both groups. According to
      baseline measurements, specific IgA levels of patients in groups I and II were
      significantly lower than that of controls. This difference disappeared at the end
      of the treatment period in both groups. CONCLUSION: SLIT seems to be effective in
      ameliorating clinical symptoms, drug consumption and bronchial hyperreactivity,
      and results in downregulation of Der-p-1-specific IgE production. Furthermore, at
      the end of SLIT, specific IgA levels, which were decreased compared to healthy
      controls initially, did no longer differ between patients and controls.

PMID- 15722640
TI  - Interferon-gamma inhibits in vitro mobilization of eosinophils by interleukin-5.
AB  - BACKGROUND: Th2 cytokines play pivotal roles in allergic inflammation, including
      eosinophilia, and their actions are antagonized by Th1 cytokines, conferring them
      therapeutic potential. METHODS: In this study, we examined the ability of a
      number of cytokines to suppress the activation of eosinophils that function as
      effector cells for allergic airway diseases. RESULTS: Interleukin (IL)-5, IL-6,
      and tumor necrosis factor (TNF) induced an eosinophil shape change, whereas
      interferon (IFN)-gamma significantly inhibited the shape change. Other cytokines,
      including IL-1beta, IL-4, IL-10 and IL-13, had little or only slightly enhancing
      or reducing effects on the shape change. We further analyzed the IFN-gamma
      effect, showing that pretreatment with IFN-gamma strongly suppressed IL-5-induced
      eosinophil shape change, and cycloheximide (CHX) abrogated the suppression by IFN
      gamma, suggesting that new protein synthesis is required for the inhibitory
      effect by this cytokine. In agreement with these results, IFN-gamma blocked the
      eosinophil migration and ERK phophorylation induced by IL-5, and the addition of
      CHX restored eosinophil chemotaxis. CONCLUSIONS: Collectively, IFN-gamma may
      attenuate eosinophilic inflammation by directly negating eosinophil mobilization.

PMID- 15722641
TI  - Group 13 allergens as environmental and immunological markers for grass pollen
      allergy: studies by immunogold field emission scanning and transmission electron
      microscopy.
AB  - BACKGROUND: Polygalacturonases were recently identified as important grass pollen
      allergens and designated group 13 allergens. The objective of the present study
      was to investigate the presence of group 13 grass pollen allergens in different
      grass species, their release and ultrastructural location in dry and hydrated
      grass pollen. METHODS: Nitrocellulose-blotted allergen extracts from 12 wild and
      cultivated grass genera were probed with a rabbit antiserum raised against
      purified recombinant timothy grass pollen allergen, Phl p 13. The release
      kinetics of Phl p 13 from timothy grass pollen hydrated for 0.5 min to 3 h were
      analyzed by immunoblotting. Phl p 13 was localized in dry and hydrated grass
      pollen grains by immunogold field emission scanning and transmission electron
      microscopy. RESULTS: Group 13 allergens were detected in all 12 wild and
      cultivated grass genera representing the major subfamilies of the Poaceae.
      Ultrastructurally, the allergen was located in the wall and in the cytoplasm of
      timothy grass pollen grains. In the cytoplasm, Phl p 13 was associated with
      polysaccharide particles and as yet undescribed stacks of microtubule-like
      structures. After hydration in rain water, pollen grains expel cytoplasmic
      particles of respirable size containing Phl p 13, which becomes detectable in
      aqueous supernatants already after 0.5 min. CONCLUSIONS: Group 13 allergens
      represent one set of marker allergens which specifically occur in pollen of the
      major grass subfamilies and are rapidly released in association with respirable
      particles after pollen hydration. They may be considered as environmental markers
      for grass pollen exposure and group 13-specific IgE antibodies as immunological
      markers for genuine grass pollen sensitization.

PMID- 15722642
TI  - Characterization of modified allergen extracts by in vitro beta-hexosaminidase
      release from rat basophils.
AB  - BACKGROUND: To date, there is no well-established test available that can be used
      to measure functional properties of modified allergens (allergoids). Due to the
      cross-linking process, the IgE-binding capacity of the allergens, normally
      necessary for their characterization, is lost. The aim of this study was to test
      whether the rat basophilic leukaemia (RBL) cell assay (beta-hexosaminidase
      release by rat basophils upon allergen stimulation) can be adopted to
      characterize allergoids and to evaluate the assay for testing allergoids and
      native allergens as well. METHODS: Mice were immunized with native and modified
      Phleumpratense extracts in the presence of alum. Their sera were used to
      sensitize RBL-2H3 cells and measure basophil stimulation induced by different
      allergen extracts in the presence or absence of various additives. RESULTS: Sera
      containing specific IgE against both extract formulations were obtained. Native
      as well as modified extracts induced dose-dependent beta-hexosaminidase release
      from RBL cells. Both extracts were used to evaluate the characteristics of the
      assay, which showed high precision. Storage conditions were chosen to enhance
      extract degradation, which could be read directly from the altered stimulatory
      capacity of the extracts. Additives turned out to have diverse effects on the
      assay, whereas phenol had no measurable effect, alum had an inhibitory effect and
      glycerol elevated basophil activation. CONCLUSIONS: For the first time, a
      reliable, precise in vitro assay is available that is able to directly measure
      the properties of modified allergen extracts after their production process. The
      test is well evaluated and its advantages and limitations are discussed in this
      report.

PMID- 15722643
TI  - Prevalence of antibody to hepatitis E virus among haemodialysis patients in
      Taiwan: possible infection by blood transfusion.
AB  - BACKGROUND/AIMS: A higher prevalence of anti-hepatitis E virus (HEV) in non
      endemic viral hepatitis such as in Germany has been reported in our previous
      study. The aim of this study was to assess the seroepidemiology of HEV among
      haemodialysis (HD) patients in Shin-Kong Hospital, Taiwan, and to evaluate
      whether there was an increased risk of infection and exposure to HEV even in an
      area of endemic viral hepatitis. METHODS: Serum samples obtained from 400
      Taiwanese patients on chronic HD (group 1), 400 sex- and age-matched healthy
      subjects (group 2) and hospital patients (group 3) were tested for the IgG anti
      HEV. RESULTS: The prevalence of anti-HEV among the HD patients and the healthy
      controls were 31 and 8.9%, respectively. The difference (22%) was statistically
      significant (p < 0.01). In comparison, the anti-HEV in hospital patients was 16%.
      CONCLUSION: The study indicated a significantly higher risk of HEV infection
      among patients on chronic HD in endemic regions of viral hepatitis such as
      Taiwan. Mostly because of anaemia, HD patients usually received packed
      transfusion (red blood cells) if their haemoglobin was low. It is possible that
      HEV infection may be transmitted through blood transfusions in an endemic area.
      In such areas, appropriate strategies should be adopted to prevent the risk of
      HEV among HD patients.

PMID- 15722644
TI  - Comparison between 1alpha(OH)D3 and 1,25(OH)2D3 on the suppression of plasma PTH
      levels in uremic patients, evaluated by the 'whole' and 'intact' PTH assays.
AB  - BACKGROUND/AIMS: The aim was to evaluate the acute effects of intravenous
      1alpha(OH)D3 and 1,25(OH)2D3 on (1) plasma parathyroid hormone (PTH) and Ca2+
      levels in chronic uremic patients and (2) circulating large C-terminal PTH
      fragments as measured by the 'whole PTH' assay compared to two different 'intact
      PTH' assays. METHODS: 11 patients on chronic hemodialysis with plasma intact PTH
      >90 pg/ml were studied. At time zero 10 microg 1,25(OH)2D3 (Calcijex, Abbott,
      USA), or 10 microg 1alpha(OH)D3 (Etalpha, LEO, Denmark) or 10 ml of isotonic
      saline was injected as a bolus. Blood samples for analyses of plasma Ca2+ and
      plasma PTH were drawn at 0, 6, 12, 24, 48 and 72 h. The same patient was studied
      3 times in a random fashion with an interval of 3 weeks. Further, 7 of the
      patients were studied after an injection of 6 microg 1,25(OH)2D3 intravenously.
      RESULTS: No significant changes in plasma Ca2+ and PTH were seen after
      administration of saline. Twenty-four hours after administration of 1,25(OH)2D3,
      plasma PTH decreased from a maximum level of PTHWHOLE 151 +/- 27 to a minimum of
      58 +/- 13 pg/ml; from a maximum level of PTHTOTAL 247 +/- 40 to a minimum of 99
      +/- 26 pg/ml and from a maximum level of PTHINTACT 205 +/- 29 to a minimum of 83
      +/- 18 pg/ml (p < 0.001). Twenty-four hours after administration of 1alpha(OH)D3,
      plasma PTH levels decreased from a maximum level of PTHWHOLE 155 +/- 21 to a
      minimum of 116 +/- 15 pg/ml; from a maximum level of PTHTOTAL 265 +/- 33 to a
      minimum of 221 +/- 35 pg/ml and from a maximum level of PTHINTACT 222 +/- 26 to a
      minimum of 182 +/- 23 pg/ml (p < 0.05). Regardless of which of the three assays
      that was applied, the percentage suppression of PTH following administration of
      1,25(OH)2D3 was approximately 60% and following administration of 1alpha(OH)D3
      approximately 20%. Significant correlations were demonstrated between the Whole
      and the intact PTH assays, and as expected between the 2 intact assays
      ('Whole'/'Intact', r = 0.92, p < 0.0001, 'Whole'/'Total', r = 0.94, p < 0.0001,
      'Intact'/'Total', r = 0.97, p < 0.0001) with no influence of the two vitamin D
      analogs administered. Plasma Ca2+ remained stable after administration of saline.
      After 24 h, no increase in plasma Ca2+ was observed after administration of
      1alpha(OH)D3 or after administration of 6 microg 1,25(OH)2D3, while plasma Ca2+
      after administration of 10 microg 1,25(OH)2D3 increased to 1.31 +/- 0.03 mmol/l
      (p < 0.008). After 72 h, 1alpha(OH)D3 increased plasma Ca2+ to 1.22 +/- 0.02
      mmol/l (p < 0.05) and 10 microg 1,25(OH)2D3 to 1.27 +/- 0.03 mmol/l. Plasma
      phosphate was within the normal range before administration of saline (1.24 +/-
      0.13 mmol/l), 1,25(OH)2D3 (1.28 +/- 0.12 mmol/l) and 1alpha(OH)D3 (1.46 +/- 0.21
      mmol/l). Plasma phosphate increased significantly after 24, 48 and 72 h to a
      maximum of 2.06 +/- 0.27 mmol/l after administration of 1,25(OH)2D3 and a maximum
      of 1.94 +/- 0.31 mmol/l after administration of 1alpha(OH)D3. Plasma phosphate
      was significantly higher after 1,25(OH)2D3 than after 1alpha(OH)D3 at 48 (p =
      0.016) and 72 h (p < 0.010). CONCLUSION: A single intravenous dose of both 10
      microg 1,25(OH)2D3 and 1alpha(OH)D3 significantly suppressed plasma PTH. The
      acute suppressive effect of 1,25(OH)2D3 was 3 times greater than that of
      1alpha(OH)D3. The increase in plasma Ca2+ after intravenous administration of 10
      microg of 1,25(OH)2D3 was, however, significantly greater than that of 10 microg
      of 1alpha(OH)D3 (p < 0.005). The PTH response to acute administration of 10
      microg of the two vitamin D analogs was in principle the same, when measured by
      the three different assays and resulted in a parallel shift of the PTH response
      curves. Thus, circulating levels of large C-terminal PTH fragments were not
      influenced by differences in plasma Ca2+ or by the vitamin D analog given.

PMID- 15722645
TI  - Multi-glycoside of Tripterygium wilfordii Hook f. ameliorates proteinuria and
      acute mesangial injury induced by anti-Thy1.1 monoclonal antibody.
AB  - BACKGROUND/AIMS: Multi-glycoside from Tripterygium wilfordii Hook f. (GTW) is
      used for various immune and inflammatory diseases including renal diseases
      represented by mesangial proliferative glomerulonephritis (MsPGN) in China.
      However, there have been no fundamental studies on the operating mechanism of GTW
      on MsPGN. The aim of this study is to examine as the first step the effects of
      GTW on acute injurious process such as mesangial injury and proteinuria in an
      acute and reversible Thy.1.1 glomerulonephritis (Thy1.1GN) model and then to
      clarify the action mechanism of GTW at molecular level by examining its effects
      on various injurious factors in this model. METHODS: Thy1.1 GN was induced in
      rats by a single intravenous injection with 500 microg of anti-Thy1.1 mAb 1-22-3.
      Daily oral administration of GTW and vehicle as a control was started from 3 days
      before injection of mAb to the day of sacrifice in each experiment. Fourteen rats
      were randomly divided into 2 groups, GTW-treated and vehicle-treated groups, and
      sacrificed on day 14 in experiment 1 or on day 7 in experiment 2 after induction
      of Thy1.1 GN. Proteinuria was determined on days 1, 3, 5, 7, 10 and 14 in
      experiment 1 or on 1, 3, 5 and 7 in experiment 2. From blood and kidneys taken at
      sacrifice, blood biochemical parameters, mesangial morphological changes,
      glomerular macrophage infiltration, and glomerular mRNA expression of cytokines
      were examined. RESULTS: In experiment 1, proteinuria and mesangial matrix
      expansion were significantly attenuated by GTW treatment. In experiment 2, GTW
      treatment significantly ameliorated proteinuria, mesangial lesions and macrophage
      accumulation in glomerulus. In addition, it significantly reduced the glomerular
      expression of mRNA for PDGF, MCP-1 and IL-2. CONCLUSION: GTW ameliorated not only
      proteinuria but also mesangial alterations in Thy1.1 GN most likely by reducing
      expression of injurious cytokines, indicating that GTW has suppressive effects on
      acute inflammatory changes in glomeruli.

PMID- 15722646
TI  - Effect of heavy metals on, and handling by, the kidney.
AB  - Heavy metals such as cadmium (Cd), mercury (Hg), lead (Pb), chromium (Cr) and
      platinum (Pt) are a major environmental and occupational hazard. Unfortunately,
      these non-essential elements are toxic at very low doses and non-biodegradable
      with a very long biological half-life. Thus, exposure to heavy metals is
      potentially harmful. Because of its ability to reabsorb and accumulate divalent
      metals, the kidney is the first target organ of heavy metal toxicity. The extent
      of renal damage by heavy metals depends on the nature, the dose, route and
      duration of exposure. Both acute and chronic intoxication have been demonstrated
      to cause nephropathies, with various levels of severity ranging from tubular
      dysfunctions like acquired Fanconi syndrome to severe renal failure leading
      occasionally to death. Very varied pathways are involved in uptake of heavy
      metals by the epithelium, depending on the form (free or bound) of the metal and
      the segment of the nephron where reabsorption occurs (proximal tubule, loop of
      Henle, distal tubule and terminal segments). In this review, we address the
      putative uptake pathways involved along the nephron, the mechanisms of
      intracellular sequestration and detoxification and the nephropathies caused by
      heavy metals. We also tackle the question of the possible therapeutic means of
      decreasing the toxic effect of heavy metals by increasing their urinary excretion
      without affecting the renal uptake of essential trace elements. We have chosen to
      focus mainly on Cd, Hg and Pb and on in vivo studies.

PMID- 15722647
TI  - Imatinib blocks spontaneous mechanical activities in the adult mouse small
      intestine: possible inhibition of c-Kit signaling.
AB  - Interstitial cells of Cajal (ICCs) are postulated to serve as pacemakers that
      physiologically generate electrical slow waves in the gastrointestinal tract.
      Imatinib is a novel and potent inhibitor of c-Kit tyrosine kinase and a new
      therapeutic agent for gastrointestinal stromal tumors (GIST) which presumably
      arise from ICCs. The effects of imatinib on the basal rhythmic mechanical
      activities of small intestinal circular muscles were investigated in ring
      preparations of the gut. The small intestinal rings of BALB/c mice exhibited
      spontaneous contractile activity at a rate of 40.8 +/- 4.9 contractions/min.
      Imatinib (1- 81 micromol/l) dose-dependently abolished spontaneous contractile
      activity in the 9- to 27-micromol/l concentration range. Contraction was restored
      by washing imatinib out with a fresh buffer. High K(+)-induced contraction was
      not affected by imatinib, suggesting that the drug does not have nonspecific
      inhibitory actions on the smooth muscles. The small intestinal rings of adult
      W/W(v)mice, which lack a functional c-Kit activity,exhibited only small and
      irregular spontaneous contractions. These results demonstrate that imatinib
      affects bowel contractions, and suggest that the c-Kit signaling of ICCs plays an
      essential role in the spontaneous movements in circular muscles of the mouse
      small intestine.

PMID- 15722648
TI  - Effect of cevimeline on salivary components in patients with Sjogren syndrome.
AB  - The aim of this study is to clarify the effects of cevimeline on various
      components in human saliva, such as immunoglobulin A (IgA), lysozyme, alpha
      amylase and squamous cell carcinoma (SCC) antigen. Twelve female patients with
      Sjogren syndrome (SS) and 14 healthy women were enrolled. After the first saliva
      collection, one capsule (30 mg) of cevimeline was administered to each subject.
      Saliva was collected again after 90 min. The salivary flow rate and concentration
      of each component were measured. In both groups the salivary flow rate and
      amylase concentration were significantly increased by cevimeline. The lysozyme
      and IgA concentrations did not change significantly in both groups. The SCC
      antigen concentration did not change significantly in the SS group, but it
      decreased significantly in the control group. The secretion rates of amylase and
      IgA showed significant increases in both groups. The secretion rate of lysozyme
      significantly increased only in the control group, while the secretion rate of
      SCC significantly increased only in the SS group. Cevimeline augments not only
      the salivary flow rate but also the secretion rate of some digestive and/or
      defense factors from infections. It may be beneficial for SS patients to continue
      taking cevimeline to prevent oral infections, and other serious sequelae.

PMID- 15722649
TI  - Capgras' syndrome of time.
AB  - The delusion that the usual passage of time has been changed and that time has
      been interfered with or is repeating itself is rare. Four patients with the
      delusion of warped time are presented and the significance of the symptom is
      discussed. The perception of the passage of time and its disorders is discussed.

PMID- 15722650
TI  - Comments on the new AHA recommendations for blood pressure measurement.

PMID- 15722651
TI  - Control of blood pressure and other cardiovascular risk factors at different
      practice settings: outcomes of care provided to diabetic women compared to men.
AB  - Cardiovascular disease (CVD) is the major cause of morbidity and mortality in
      diabetes. To determine the proportion of patients who met the American Diabetes
      Association guidelines for control of CVD risk factors and to assess the
      achievement of these guidelines in women compared with men, we conducted a cross
      sectional study of 3678 diabetic cohorts followed at seven medical centers, two
      Veteran Administration hospitals, three urban clinics, and two suburban clinics.
      Overall, 28% met the target blood pressure of <130/80 mm Hg, 48.8% achieved a
      goal low-density lipoprotein cholesterol of <100 mg/dL, and 35.8% had hemoglobin
      A1c of <7%. Gender comparisons of 2788 diabetic patients at urban and suburban
      centers showed that women had a lower percentage of low-density lipoprotein
      cholesterol <100 mg/dL (45.8 vs. 51.3, p<0.01) and a lower percentage of
      screening for retinopathy (54 vs. 60, p<0.01) and nephropathy (37 vs. 49,
      p<0.01). However, overall there were no gender differences in the percentage of
      patients who achieved a goal blood pressure <130/80 mm Hg or hemoglobin A1c <7%.
      Control of blood pressure and other CVD risk factors in diabetic patients was
      largely suboptimal, especially for diabetic women. These observations underscore
      the need for better strategies for control of CVD risk in the diabetic population
      in general, and women in particular.

PMID- 15722652
TI  - Prescribing patterns of diuretics in multi-drug antihypertensive regimens.
AB  - Recent literature suggests that most hypertensives will require two or more drugs
      to achieve target blood pressure. Our objective was to estimate the proportion of
      patients receiving diuretics, including thiazides, for blood pressure control
      among those receiving two or more drugs. We studied 25,052 hypertensives in a
      tertiary care Veterans Affairs facility and identified individuals taking any
      thiazide or loop diuretic among patients receiving two, three, four, or more
      drugs. Rates of any diuretic use were 50%, 73%, and 89%, and decreased to 39.0%,
      59.0%, and 72.5% for thiazide use, respectively. Rates of thiazide use were
      statistically significantly higher among African Americans compared with the
      general study population, but did not differ significantly in the elderly. Though
      overall diuretic use seems to be increasing as compared with previous studies,
      there is room for improvement in the use of thiazides in multi-drug hypertension
      regimens.

PMID- 15722653
TI  - New-onset diabetes in treated hypertensive patients--is it clinically
      significant? Roundtable discussion.

PMID- 15722654
TI  - Combination therapy in the management of hypertension: focus on angiotensin
      receptor blockers combined with diuretics.
AB  - There is increasing evidence that combination therapy should be emphasized more
      than it is at present for the initial treatment of hypertensive patients. Recent
      guidelines acknowledge the value of combination therapy, although some treatment
      algorithms fail to echo this message. Observations from major clinical trials in
      the elderly, diabetics, stroke patients, and African Americans all indicate that
      combination therapy is necessary to control blood pressure in the majority of
      these patients. Several combination therapies such as an angiotensin II receptor
      blocker and a diuretic, an angiotensin-converting enzyme inhibitor with a
      diuretic, a beta blocker with a diuretic, or an angiotensin-converting enzyme
      inhibitor with a calcium antagonist have been shown to be effective in patients
      who do not respond to monotherapy. The current review focuses on the newest such
      combination; an angiotensin II receptor blocker and a diuretic may have an added
      advantage of being well tolerated. Recent studies have shown that angiotensin II
      receptor blockers, given alone or combined with a diuretic, may prevent some
      cardiovascular outcomes independent of their blood pressure-lowering efficacy.

PMID- 15722655
TI  - Recommendations for blood pressure measurement in humans: an AHA scientific
      statement from the Council on High Blood Pressure Research Professional and
      Public Education Subcommittee.

PMID- 15722656
TI  - Treatment of diabetic hypertensive patients: results of a national survey.

PMID- 15722657
TI  - Diuretics should continue to be one of the preferred initial therapies in the
      management of hypertension: the argument for.

PMID- 15722658
TI  - Diuretics should continue to be one of the preferred initial therapies in the
      management of hypertension: the argument against.

PMID- 15722659
TI  - Measurement of blood pressure in and out of the office.

PMID- 15722660
TI  - Nonarteritic anterior ischemic optic neuropathy.
AB  - Nonarteritic anterior ischemic optic neuropathy is a common cause of sudden,
      painless loss of vision present commonly on awakening from sleep. It most
      commonly affects middle-aged and elderly Caucasian men and women. Involvement of
      the opposite eye occurs within 3 years in less than 43% of patients.
      Hypertension, diabetes, and nocturnal hypotension are risk factors. A congenital
      small cup-to-disk ratio also predisposes to the optic nerve ischemia. There is no
      effective therapy to treat patients acutely or to prevent recurrence. After 6
      months of careful follow-up, 57.3% of patients will have no significant change or
      worsening of their vision in the involved eye.

PMID- 15722661
TI  - Muscle cramps and diuretic therapy.

PMID- 15722664
TI  - Outcomes and prognostic factors of systolic as compared with diastolic heart
      failure in urban America.
AB  - We sought to describe a large heart failure (HF) population with respect to
      systolic and diastolic abnormalities in terms of demographics, echocardiographic
      parameters, and survival. Using data abstracted from the Resource Utilization
      Among Congestive Heart Failure (REACH) study, a targeted subpopulation of 3471
      patients had electrocardiographic, echocardiographic, and clinical data taken
      from automated sources during the first year of diagnosis. Among the HF
      population, 1811 (52.2%) had diastolic HF. Prevalence of diastolic HF trended
      with age, from 46.4% in those less than 45 years to 58.7% in those 85 years or
      older (p=0.001 for trend). Patients with diastolic HF had a higher mean ejection
      fraction (55.7% vs. 28.0%), lower left ventricular end-systolic diameter (3.11
      vs. 4.74 cm), and lower left atrium:aortic outlet ratio (1.28 vs. 1.38) (p=0.001
      for each comparison). Annualized age, sex, and race-adjusted mortality were 11.2%
      and 13.0% for those with diastolic and systolic HF, respectively (p=0.001). In a
      large, racially mixed, urban HF population, those with diastolic HF predominate
      and enjoy better-adjusted survival than counterparts with systolic HF.

PMID- 15722665
TI  - Mineralocorticoid receptor is overexpressed in cardiomyocytes of patients with
      congestive heart failure.
AB  - Mineralocorticoid receptors (MRs) have been identified in the human
      cardiovascular tissues. We determined MR expression in the failing heart to
      clarify the mechanism of action of aldosterone antagonist in the treatment of
      congestive heart failure. MR protein and MR mRNA content were detected by
      immunohistochemical staining and in situ hybridization in the cardiac tissues.
      Immunohistochemical staining of the receptor, as well as in situ hybridization of
      MR mRNA, was dense in cardiomyocytes of the failing left ventricle as compared
      with the controls. The staining ratio of the cytoplasm to the interstitium showed
      that MRs were located mainly in the cytoplasm. The cytoplasm to the interstitium
      in the failing left ventricle was 1.53+/-0.13, which was significantly higher
      than that of the controls 1.25+/-0.19 (p<0.05). These findings suggest that the
      efficacy of aldosterone antagonists in treating congestive heart failure may be
      in part through blocking the MRs, which are upregulated in the failing heart.

PMID- 15722666
TI  - Utility of impedance cardiography to improve physician estimation of hemodynamic
      parameters in the emergency department.
AB  - Emergency physicians must often make assessments of complex hemodynamic
      parameters. To assess the utility of impedance cardiography (ICG) in the
      emergency department, the authors examined treating physicians' abilities to
      assess stroke volume (SV), cardiac output (CO), and systemic vascular resistance
      (SVR) by comparing the clinicians' estimates of these values to ICG measurements.
      Treating physicians were asked to estimate the SV, CO, and SVR of acutely ill
      patients as being low, normal, or high. ICG measurements of SV, CO, and SVR were
      also categorized as low, normal, or high. Physician estimates were compared with
      ICG measures for concordance. Changes of therapy initiated as a result of
      discordance between physician's estimates and ICG measurements were recorded. The
      treating physician assessments and ICG hemodynamic measurements were concordant
      in 62 of 101 (62%) cases for SV (kappa=0.068), in 53 of 101 (53%) cases for CO
      (p=0.125), and in 50 of 101 (50%) measurements for SVR (p=0.148). The low
      concordance suggests that treating physicians did not consistently estimate SV,
      CO, and SVR accurately. ICG provides noninvasive hemodynamic measurements of SV,
      CO, and SVR that offer clinical utility and potential value in the emergency
      department.

PMID- 15722667
TI  - Novel therapies for heart failure: vasopressin and selective aldosterone
      antagonists.
AB  - Despite favorable improvements in mortality, heart failure (HF) remains a
      problematic illness due to the ever-present burden of hospitalization. Clearly,
      novel treatment strategies are needed. This review focuses on two newer
      pharmacologic targets: arginine vasopressin and aldosterone. Arginine vasopressin
      receptor antagonists will most likely serve as an adjunct to or replacement of
      standard diuretic therapy in selected patients. The safety and efficacy of
      chronic therapy with oral arginine vasopressin receptor antagonists in large
      groups of congestive HF patients is currently under investigation. Aldosterone
      antagonism is emerging as a treatment of severe congestive HF. Recent large-scale
      clinical trials using aldosterone antagonists have proven that those with HF or
      left ventricular dysfunction postmyocardial infarction derive a survival benefit
      from aldosterone antagonism. Whether aldosterone antagonism should be prescribed
      in all patients with HF is unclear; however, in carefully selected and managed
      patients, aldosterone antagonism is helpful.

PMID- 15722668
TI  - A review of the renal and neurohormonal effects of B-type natriuretic peptide.
AB  - Adverse neurohormonal activation is an essential component in the pathogenesis of
      acute decompensated congestive heart failure (CHF). Consequently, blunting this
      activation is an important therapeutic goal. B-type natriuretic peptide (BNP) is
      a counterregulatory hormone produced by the ventricles in response to pressure
      and volume load. Endogenous BNP levels are significantly elevated in patients
      with acute CHF, but these levels are frequently inadequate to overcome the excess
      neurohormonal activation present in this condition. Infusion of nesiritide, a
      recombinant form of endogenous human BNP, increases circulating BNP levels by
      several-fold, augmenting the counterregulatory effects of this hormone. Clinical
      trials demonstrate that in patients with acute decompensated CHF, nesiritide
      produces arterial and venous vasodilation, reducing both preload and afterload;
      blunts adverse neurohormones, including renin, aldosterone, norepinephrine, and
      endothelin-1; and improves renal hemodynamics and tubular function. As a result,
      nesiritide quickly reduces clinical symptoms and improves mortality in patients
      with acute CHF.

PMID- 15722669
TI  - The COMET trial.

PMID- 15722670
TI  - Difficult cases in heart failure: polycystic ovary syndrome and heart failure.
AB  - This is a case of a 21-year-old female with a history of polycystic ovary
      syndrome who was subsequently diagnosed with heart failure. The patient did not
      have a family history of heart failure, nor did the patient herself have evidence
      of ischemic or valvular heart disease or prior viral infection. The patient was
      found, upon further evaluation, to have significant obstructive sleep apnea, a
      condition that has been linked to the development and/or worsening of heart
      failure. Interestingly enough, recent evidence has revealed that patients with
      polycystic ovary syndrome have been found to have a predilection for developing
      obstructive sleep apnea, irrespective of body weight or habitus.

PMID- 15722671
TI  - Insurers, hospitals, employers... patients and doctors.

PMID- 15722673
TI  - The diagnostic evaluation of pulmonary embolism.
AB  - Due to the morbidity and mortality associated with either untreated disease or
      inappropriate anticoagulant therapy, accurate diagnosis of pulmonary embolism is
      essential. Pulmonary angiography, the current gold standard test for diagnosing
      pulmonary embolus, is both invasive and costly; therefore, noninvasive diagnostic
      strategies have been developed. Noninvasive tests often have to be combined to
      either raise the posttest probability of disease to a level justifying treatment
      or lower it to a level at which withholding treatment is warranted. Diagnostic
      algorithms involving clinical assessment; venous ultrasonography; D-dimer
      testing; ventilation-perfusion lung scanning; and, more recently, computed
      tomography have been validated in management trials of patients with a suspected
      pulmonary embolism. The optimal strategy at individual institutions is dependent
      on local availability, expertise, and cost. Magnetic resonance imaging and
      combined computed tomographic pulmonary angiography and venography possess the
      potential to be used as stand-alone tests for pulmonary embolism but require
      further evaluation.

PMID- 15722672
TI  - Proc, Dr. Sam, Uncle Henry, and the "Little Green Book". Interview by Charles F.
      Wooley.
AB  - During his house staff training before World War II, Dr. W. Proctor Harvey
      encountered Dr. Samuel A. Levine at the Peter Bent Brigham Hospital in Boston.
      Following military service, Harvey returned to Boston and became Levine's first
      cardiology fellow. The book Clinical Auscultation of the Heart--the Little Green
      Book by Levine and Harvey in 1949 combined Levine's clinical wisdom with Harvey's
      objective phonocardiographic methods and brought an important objective dimension
      to the art of cardiac auscultation. Both Levine and Harvey shared experiences and
      friendship with Henry Christian, the first Physician-in-Chief when the new
      Brigham Hospital Opened in 1913. Christian, appointed Dean of the Harvard Medical
      School in 1908 at the age of 32, was referred to as the "Boy Dean." He held the
      Hersey Chair of Theory and Practice of Physic from 1908 until 1939, was one of
      the founding group of the American Society for Clinical Investigation, and a
      major force in academic medicine. Levine served as intern to Christian and then
      joined the Brigham medical staff in 1915. Proctor Harvey followed Henry
      Christian's path from their mutual hometown of Lyunchburg, VA to the Peter Bent
      Brigham Hospital. A series of illuminating and respectful professional
      interactions--initially between Christian and Levine, between Levine and Harvey
      in the early 1940s, and between Harvey and Christian in the 1950s--provide the
      background for the genesis of the Little Green Book and a remarkable example of
      academic heritage.

PMID- 15722674
TI  - Integrating sleep medicine into a cardiology practice.
AB  - The sequelae of sleep-disordered breathing is encountered on a daily basis by the
      general cardiology practitioner. This includes arterial and pulmonary
      hypertension, congestive heart failure, atrial arrhythmias, and possibly vascular
      disease. Recognition, diagnosis, and treatment of sleep-disordered breathing is
      relatively straightforward and can be smoothly incorporated into an existing
      cardiology practice.

PMID- 15722675
TI  - Antitrust law and a tale of two health care industries.

PMID- 15722676
TI  - Medical liability crisis: one Illinois physician's perspective.

PMID- 15722677
TI  - Charity care: not getting what we pay for.

PMID- 15722678
TI  - Not-for-profit hospital billing and collection: resisting quick legal fixes.

PMID- 15722679
TI  - Costs, charges, and medical debt: what is the real goal?

PMID- 15722680
TI  - "The value of your care, doctor".

PMID- 15722681
TI  - It is not I.

PMID- 15722682
TI  - The case for heart hospitals with physician investors.

PMID- 15722683
TI  - Why I supported the "specialty hospital moratorium".

PMID- 15722684
TI  - Echocardiographic assessment of mitral stenosis: diagnosis, severity, management.

PMID- 15722685
TI  - The complementary role of CT coronary angiography and myocardial perfusion
      imaging.

PMID- 15722686
TI  - Tombstone ST segments.

PMID- 15722687
TI  - J wave in hypothermia and during rewarming.

PMID- 15722688
TI  - Physical activity as anti-inflammatory therapy for cardiovascular disease.

PMID- 15722690
TI  - Achieving National Cholesterol Education Program goals in coronary artery
      disease.
AB  - National Cholesterol Education Program (NCEP) guidelines recommend low-density
      lipoprotein cholesterol (LDL-C) levels <100 mg/dL for patients with coronary
      artery disease (CAD) and lipid-lowering therapy if LDL-C remains >100-130 mg/dL
      after dietary intervention. Studies consistently report that the majority of CAD
      patients do not achieve NCEP goals in clinical practice; we sought to determine
      if our practice fared better. We performed a retrospective chart review of 600
      CAD patients followed by cardiologists. The mean age was 69, and 66% of patients
      were male. Of persons with a cardiology clinic lipid profile (60%), most (76%)
      achieved an LDL-C <100 mg/dL; however, only 61% were treated to the NCEP
      secondary goal of non-HDL-C <130 mg/dL. Of patients not at an LDL-C goal, 81%
      were on lipid-lowering therapy, but only 18% were on maximal statin doses and 6%
      on combination therapy. We concluded that the majority of CAD patients have had
      recent lipid measurements and are treated according to NCEP guidelines, but many
      patients remain on suboptimal therapy.

PMID- 15722689
TI  - Knowledge of cholesterol levels and targets in patients with coronary artery
      disease.
AB  - Little is known about the extent to which patients are aware of nationally
      recommended cholesterol and lipid subfraction targets. The authors interviewed
      738 patients hospitalized with coronary artery disease to assess their knowledge
      of their low-density lipoprotein, high-density lipoprotein, and total cholesterol
      levels as well as corresponding national targets. Only 8%, 8%, and 43% of
      patients could recall their low-density lipoprotein, high-density lipoprotein,
      and total cholesterol values, respectively. Only 5%, 2%, and 50% could correctly
      name targets for these values. Knowledge of cholesterol targets was particularly
      poor among women, nonwhites, and patients without any college education. Patients
      with multiple cardiac risk factors and patients with a previous history of
      cardiovascular disease were no more knowledgeable about their cholesterol targets
      than those without these conditions. These findings suggest that current
      cholesterol education efforts appear inadequate, particularly for women,
      nonwhites, and patients without any college education.

PMID- 15722691
TI  - Prevalence of cardiovascular risk factors in selected samples of schoolchildren-
      socioeconomic influence.
AB  - Few data are available regarding the prevalence of cardiovascular risk factors in
      schoolchildren in Brazil. Weight, height, body mass index, blood pressure, and
      serum cholesterol were determined in 366 students, from 6-12 years of age, 209
      (57.1%) from a private school and 157 (41.9%) from a public school, 187 (51.1%)
      female, aged 8.4+/-1.7 years. Prevalence of the risk of being overweight was
      14.8%, being overweight/obese 13.1%, and presenting with elevated cholesterol
      (>/=170 mg/dL) was 28.1%, particularly at the private school: 21.5% vs. 5.7% for
      the risk of being overweight (p<0.001), 17.2% vs. 7.6% for being overweight/obese
      (p<0.01), 41.8% vs. 10.2% for cholesterol >/=170 mg/dL (p<0.001), and 14.8% vs.
      1.3% for cholesterol >/=200 mg/dL (p<0.001), respectively. The results showed a
      high prevalence of risk factors among these school children, especially among
      private students.

PMID- 15722692
TI  - Dietary protein type and cardiovascular disease risk factors.
AB  - Observational studies suggested a negative association between vegetable protein
      and cardiovascular disease risk, whereas intervention studies have been less
      consistent. The majority of interventional studies that have evaluated the
      effects of soy protein compared to animal protein have used casein. Relative to
      casein, the effect of soy protein on lipids and lipoprotein appears to be
      variable and less dramatic than originally reported. When compared to animal
      proteins other than casein, relatively large intakes of soy protein (>/=25 g/d)
      appear to have a consistent, albeit small ( asymptotically equal to 5%),
      hypocholesterolemic effect. When assessed, no consistent additional benefit of
      soy protein on other cardiovascular disease risk factors; Lp(a), inflammatory
      markers, biomarkers of oxidative stress and endothelial function, has been
      reported. The data available on the effect of dietary protein on plasma lipids,
      lipoprotein levels, and cardiovascular disease risk factors is difficult to
      interpret and insufficient to account for the discrepancy between the
      observational and interventional studies.

PMID- 15722694
TI  - Intensified screening and treatment of the metabolic syndrome for cardiovascular
      risk reduction.
AB  - The metabolic syndrome (MetS), characterized by a clustering of risk factors
      associated with insulin resistance and abdominal obesity, is associated with an
      increased risk of coronary heart disease and cardiovascular disease mortality.
      Persons with MetS have a wide spectrum of coronary heart disease risk and
      appropriate evaluation of risk using global risk algorithms. Measurement of other
      risk markers and subclinical disease is potentially needed to best set treatment
      goals and accompanying treatment regimens. The presence of MetS risk factors
      should be considered in global risk assessment. Clinical management emphasizes
      addressing underlying risk factors predisposing to MetS-specifically
      overweight/obesity and physical inactivity. Further recommendations are given for
      clinical risk factors, including atherogenic dyslipidemia, elevated blood
      pressure, insulin resistance/hyperglycemia, prothrombotic state, and
      proinflammatory state. Clinicians are recommended to assess MetS in their routine
      practice and to intensify efforts to adequately treat accompanying lifestyle and
      clinical risk factors.

PMID- 15722693
TI  - What proportion of stroke is not explained by classic risk factors?
AB  - Ischemic stroke is a complex entity with multiple etiologies and variable
      clinical manifestations. The most frequent cause of stroke is atherosclerosis of
      cerebral vasculature followed by cardioembolism. Two thirds of strokes are
      explained by identifiable risk factors. Age, hypertension, and nonvalvular atrial
      fibrillation are by far the most frequent and well documented ones. Approximately
      5% of strokes are caused by conditions other than atherosclerosis or heart
      disease, i.e., cervical arteries dissections, nonatherosclerotic vasculopathies,
      infectious or systemic vasculitis, and collagen vascular diseases. In spite of a
      thorough diagnostic evaluation, 30% of strokes remain cryptogenic, i.e., no
      specific cause is identified and the classic risk factors are not present.
      Identification of unknown environmental or genetic risk factors should be the
      subject of further research.

PMID- 15722696
TI  - CARDS and A to Z.

PMID- 15722695
TI  - Moderate or vigorous intensity exercise: which is better for improving aerobic
      fitness?

PMID- 15722697
TI  - Traditional cardiac risk factors: the gun is still smoking.

PMID- 15722698
TI  - Level of adherence to National Cholesterol Education Program (NCEP); Adult
      Treatment Panel III Guidelines: are we doing it right?

PMID- 15722699
TI  - Developing a computer algorithm to identify epilepsy cases in managed care
      organizations.
AB  - The goal of this study was to develop an algorithm for detecting epilepsy cases
      in managed care organizations (MCOs). A data set of potential epilepsy cases was
      constructed from an MCO's administrative data system for all health plan members
      continuously enrolled in the MCO for at least 1 year within the study period of
      July 1, 1996 through June 30, 1998. Epilepsy status was determined using medical
      record review for a sample of 617 cases. The best algorithm for detecting
      epilepsy cases was developed by examining combinations of diagnosis, diagnostic
      procedures, and medication use. The best algorithm derived in the exploratory
      phase was then applied to a new set of data from the same MCO covering the period
      of July 1, 1998 through June 30, 2000. A stratified sample based on ethnicity and
      age was drawn from the preliminary algorithm-identified epilepsy cases and non
      cases. Medical record review was completed for 644 cases to determine the
      accuracy of the algorithm. Data from both phases were combined to permit
      refinement of logistic regression models and to provide more stable estimates of
      the parameters. The best model used diagnoses and antiepileptic drugs as
      predictors and had a positive predictive value of 84% (sensitivity 82%,
      specificity 94%). The best model correctly classified 90% of the cases. A stable
      algorithm that can be used to identify epilepsy patients within MCOs was
      developed. Implications for use of the algorithm in other health care settings
      are discussed.

PMID- 15722701
TI  - Physician use of disease management programs.
AB  - This paper examines differences in availability, use, and perceived usefulness of
      disease management programs as reported by generalist and specialist physicians
      functioning as primary care providers in health plans. Implications of these
      differences are discussed in terms of the three types of purchasers: private
      insurers, Medicare, and Medicaid. The design is a cross-sectional mail and
      telephone mixed-mode survey. The data come from 23 health plans in five states
      (Florida, New York, Colorado, Pennsylvania, and Washington), including six
      metropolitan areas: Seattle, New York City, Miami, Pittsburgh, Philadelphia, and
      Denver. The study participants are 1,244 generalist and specialist physicians who
      contracted with health plans as primary care providers. They were drawn from a
      2001 mail and telephone survey of 2,105 generalist and 1,693 specialist
      physicians serving commercial, Medicaid, and Medicare patients. Physician
      responses about use of disease management for their patients in the health plan
      and how useful they thought it was were regressed on physician, physician
      organization, and physician-health plan relationship characteristics. While
      generalist physicians are likely to report having disease management programs
      available and using them, specialists vary greatly in their response to the
      disease management programs. In contrast to physicians associated with commercial
      plans, implementation of disease management programs among physicians associated
      with Medicaid plans varied across states. Primary care providers trained in
      generalist areas of practice are more likely than specialists functioning as
      primary care providers to report that disease management programs are available
      and to use them. They also find them more useful than do specialists.

PMID- 15722700
TI  - Intensive telephone follow-up to a hospital-based disease management model for
      patients with diabetes mellitus.
AB  - The objective of this study was to evaluate the value of an intensive telephone
      follow-up as an additional component of a diabetes disease management program
      already shown to be effective in improving glycemic control, adherence with
      American Diabetes Association (ADA) standards of care, and health-related quality
      of life (HRQOL). The study involved a randomized controlled trial. The
      intervention group received a series of 12 weekly phone calls reinforcing base
      education and self-management skills. Five hundred and seven consenting patients,
      age 18 years or older, with type 1 or type 2 diabetes mellitus referred to the
      hospital- based disease management program who had telephones and were able to
      complete surveys in English or Spanish were enrolled. Outcomes were evaluated at
      3 and 12 months follow- up. Adherence to ADA standards of care, specifically
      annual eye exams, physician foot exams, foot self-exams, and pneumonia
      vaccination were significantly better with the added telephone intervention, but
      there were no differences between the groups on glycemic control, HRQOL, or
      patient satisfaction. The effectiveness of the disease management program was
      replicated with sustained improvement in glycemic control, HRQOL, and adherence
      to ADA standards. The additional telephone intervention further improved
      adherence to ADA guidelines for self-care and medical care but did not affect
      glycemic control or HRQOL.

PMID- 15722702
TI  - A matched-cohort study of health services utilization outcomes for a heart
      failure disease management program.
AB  - Chronic disease is the leading cause of illness, disability, and death in the
      United States, affecting nearly 100 million Americans. Heart failure alone
      affects nearly 4.9 million Americans, with another 550,000 newly diagnosed cases
      each year. The aim of this study was to investigate the program effects of a
      heart failure care support program. A two-group cohort study matching on
      propensity scores was used to investigate 277 heart failure care support program
      participants and corresponding matched non-participants. Measures used were rates
      of hospitalizations, emergency department visits, physician office visits, and
      heart failure-related prescription drug use and procedures. Relative to the
      matched control group, program participants experienced 26.3% (p = 0.023) fewer
      inpatient admissions, 37.9% (p = 0.018) inpatient bed days, 33.3% (p = 0.059)
      more beta blocker use, 76.7% (p = 0.048) more alpha blocker use, 22.2% (p =
      0.006) more lipid panels, 13.4% (p = 0.019) more electrocardiographies, 50.0% (p
      = 0.008) fewer cardiac catheterizations, and 94.6% (p = 0.014) more pneumonia
      vaccinations. The current study employs a propensity score matching methodology
      to select a subset of comparison patients most comparable to treatment patients,
      and documents the beneficial health services outcomes of participation in a heart
      failure care support program.

PMID- 15722703
TI  - Accuracy of prediction models in the context of disease management.
AB  - There has been a significantly increased interest in the adoption of prediction
      modeling by many disease and case management programs to risk stratify members in
      order to optimize the utilization of available clinical resources. Before
      adopting any prediction model, it is critical to understand how to evaluate the
      model's accuracy. This paper explains the basic concepts of prediction accuracy,
      the relevant parameters, their drawbacks, and their interpretations. It also
      introduces a new accuracy parameter termed "cost concentration," which indicates
      the model accuracy more explicitly in the context of disease management.

PMID- 15722704
TI  - Impacts of a government-sponsored outpatient-based disease management program for
      patients with asthma: a preliminary analysis of national data from Taiwan.
AB  - In response to the high prevalence rates, mortality rates, and rising medical
      cost of asthma, the Bureau of National Health Insurance (BNHI) initiated a
      Healthcare Quality Improvement Program (HQIP) for people with asthma. The aim of
      this study was to investigate a preliminary analysis of the impact of a
      government-sponsored, outpatient-based disease management programs for people
      with asthma on the economic outcomes, the physician's and the patient's
      satisfaction. Using a retrospective design, a 1:4 (intervention vs. control
      group) matched cohort study design was used. Comparison of 1-year pre/post tests
      of utilizations of healthcare resources were conducted for 854 already diagnosed
      cases of patients with asthma. Comparison of independent tests between the
      intervention group and control group were performed for already diagnosed cases
      (n = 854) and newly-diagnosed cases (n = 231). Valid surveys were received from
      212 physicians who participated the program, for a response rate of 46.0%, and
      642 patients who enrolled in the program, for a response rate of 27.70%. Results
      indicated that the intervention group of already diagnosed cases had 39.94% fewer
      ED visits, 46.31% fewer inpatient visits, and 51.74% shorter length of stay, at a
      significant level. Though the HQIP program for people with asthma appeared to
      reduce medical care resource utilization for the intervention group, the control
      groups showed similar reductions but in different magnitude. For the newly
      diagnosed group, the intervention group had 197.43% more outpatient visits and
      61.19% fewer ED visits of than those of the control group at a significant level.
      A majority of physicians (70%-85%) had positive opinions toward the HQIP program,
      but they admitted that the HQIP program prolonged the consultation time in
      outpatient visits (79.1%), and only 29.7% physicians did not feel interfered with
      while carrying out the HQIP. More than 80% of the patients showed positive
      feedback to the HQIP. The majority of the patients substantially adhered to
      physicians' suggestions, and had more accurate knowledge of and better self-care
      skills concerning asthma. These results have significance for the design of
      future programs aimed at improving the care of people with asthma and other
      chronic diseases in BNHI, Taiwan.

PMID- 15722779
TI  - Pain science and rational polypharmacy: an historical perspective.

PMID- 15722780
TI  - Pharmacotherapy of complex regional pain syndrome.
AB  - Complex regional pain syndrome has both nociceptive/inflammatory and neuropathic
      elements and is always (by definition) associated with abnormal activity of the
      sympathetic nervous system. There is good evidence that complex regional pain
      syndrome, as currently conceptualized, ultimately includes central sensitization
      and has motor abnormalities. The lack of a standard diagnostic test or a specific
      mechanistically based diagnostic scheme has hindered the conduct of well-designed
      trials, and to date, there is very little evidence supporting an effective
      treatment. Fortunately, some randomized, controlled trials of drug therapies have
      been conducted, and systematic reviews have been published of related neuropathic
      conditions, from which the results have been extrapolated to clinical use in
      complex regional pain syndrome. The following article presents an overview of
      available data regarding drug and interventional treatment options for complex
      regional pain syndrome and of those relevant pharmacotherapies we can derive from
      the neuropathy literature. As with most chronic pain syndromes, pharmacotherapy
      coupled with functional restoration and an interdisciplinary approach to
      treatment are essential to a successful outcome.

PMID- 15722781
TI  - Management of chronic low back pain.
AB  - Chronic low back pain is common. It presents a clinical challenge with widespread
      implications for resource utilization on a national scale. The causes of chronic
      low back pain may be mechanical or nonmechanical, nociceptive or neuropathic.
      Diagnosis is problematic because available tools lack both specificity and
      sensitivity. In rare instances, the cause of chronic low back pain can be
      attributed to an identified cause. Comprehensive pain management relies on the
      use of pharmacotherapy, physical therapy, and a multidisciplinary approach to
      treatment. Recent studies have shown a benefit for traditional adjunctive
      therapies and interdisciplinary treatment. Antidepressants and opioids have been
      and remain key elements for medical management, and some recently developed
      therapies have shown promising results in clinical trials. The following article
      presents an overview of evidence-based management for chronic low back pain, with
      an emphasis on pharmaceutical therapies.

PMID- 15722782
TI  - Management of peripheral neuropathic pain.
AB  - Neuropathic pain results from a variety of medical conditions encountered in
      physiatric practice, including infection, trauma, metabolic abnormalities, and
      nerve compression. Unlike pain resulting from nociceptive or inflammatory
      processes, neuropathic pain is associated with primary lesion or dysfunction of
      the nervous system itself and is often difficult to treat. Existing treatment
      options include drug therapy (e.g., anticonvulsants, the lidocaine patch 5%,
      antidepressants, opioids, tramadol) or interventional treatments (e.g.,
      peripheral or neuraxial nerve blockade, implanted spinal cord stimulators,
      implanted intrathecal catheters). The following article presents an overview of
      the cellular mechanisms associated with neuropathic pain, summarizes the results
      of randomized, controlled trials with the major classes of available drugs, and
      discusses treatment options that provide a rational basis for pharmacotherapy.

PMID- 15722783
TI  - Issues in opioid management.
AB  - Although a universal consensus has evolved concerning the utility of opioids in
      cancer pain, the use of opioids for the treatment of chronic nonmalignant pain
      syndromes is much debated in the medical literature. Although for clinical,
      regulatory, and medicolegal reasons, many clinicians disagree with their use,
      others find them helpful, with little prevalence of abuse behaviors or
      intolerable adverse effects. In a review of this topic, several issues of
      relevance to management decisions, including efficacy, medication compliance, and
      safety, are evaluated. As a clinically distinct population among chronic pain
      sufferers, patients with arthritis-associated pain (including rheumatoid and
      osteoarthritis) are discussed separately. Particularly important issues with
      regard to prescribing decisions, including divergent goals and expectations, and
      factors associated with avoidance of withdrawal and addiction, are also evaluated
      to ensure that management of patients with nonmalignant chronic pain is optimized
      when opioids are considered.

PMID- 15722784
TI  - Polypharmacy treatment approaches to the psychiatric and somatic comorbidities
      found in patients with chronic pain.
AB  - This review outlines the following: psychiatric and somatic comorbidities
      associated with chronic pain and their relationship to polypharmacy treatment,
      indications for polypharmacy in chronic pain, criteria for rational polypharmacy,
      basic principles of polypharmacy for pain-associated comorbidity, and, based on
      the above, psychopharmacologic polypharmacy treatment approaches to these chronic
      pain-associated comorbidities.

PMID- 15722785
TI  - Rational integration of pharmacologic, behavioral, and rehabilitation strategies
      in the treatment of chronic pain.
AB  - Historically, the concept of a mind-body duality in medicine, which supports a
      biomedical approach to pain management, has impeded the development of adequate
      treatments for persistent pain conditions and diseases. Although usually there is
      an initiating pathophysiologic nociceptive cause of pain, over time, the
      conditioning of neurophysiologic and affective systems by environmental and
      internal events can promote chronicity and frustrate the efforts of physicians to
      attenuate nociceptive processes. A full elucidation of the environmental and
      psychological factors contributing to pain and suffering may prove difficult
      using a traditional biomedical approach. Prevention of chronicity, by early
      identification and treatment of pain generators and the pain response to tissue
      injury and by recognition of those general factors that contribute to risk for
      chronicity (e.g., depressive illness, poor pain control), is crucial for any
      healthcare system that wishes to reduce the morbidity and costs of persistent
      pain. Goal-directed, outcomes-focused biopsychosocial treatment plans that
      efficiently integrate physical, behavioral, and medical approaches more
      frequently achieve better pain control and improved function. The following
      article presents a general overview of evidence for effectiveness of these
      approaches and some central principles of integrated treatment planning.

PMID- 15722786
TI  - Immunohistochemical findings in embryonal small round cell tumors with molecular
      diagnostic confirmation.
AB  - The diagnosis of pediatric tumors relies heavily on immunohistochemical staining
      of small tissue biopsies, since many entities share a "small blue cell"
      phenotype. More recently, molecular genetic analysis for detection of specific
      gene fusion products has become available. With the increased use of such
      molecular techniques, the authors have noted that tumors with proven molecular
      diagnoses can exhibit unusual patterns of immunohistochemical staining. This
      study examines pediatric tumors with a "small blue cell" phenotype in which
      molecular diagnoses were available where applicable. A panel of
      immunohistochemical stains was performed (S100, CD56, NB84, CD99 [MIC2], Bcl-2,
      CD117, CD34, desmin, MNF116, and WT1). In the 370 sections from 37 cases, all
      primitive neuroectodermal tumors, with and without the presence of t(11;22),
      demonstrated uniform membranous membrane staining with CD99 (MIC2) and focal
      staining with CD56, NB84, MNF116, and WT1. All rhabdomyosarcomas, both alveolar
      and embryonal, demonstrated uniform desmin, CD56, and cytoplasmic WT1
      immunostaining. Desmoplastic small round cell tumors showed positive cytokeratin
      staining, with half having "dot-like" cytoplasmic desmin and WT1 positivity; some
      showed focal positivity for NB84, CD99, and Bcl-2. The "undifferentiated"
      sarcomas showed the widest range of staining, with no marker staining all cases.
      Neuroblastomas exhibited uniform strong staining for CD56 and NB84 and marked
      cytoplasmic Bcl-2 positivity, and some cases showed cytoplasmic WT1 expression.
      Blastematous Wilms' tumors showed uniform strong membranous staining for CD56,
      uniform cytoplasmic staining for Bcl-2, and nuclear expression of WT1. Embryonal
      pediatric malignancies can demonstrate apparently nonspecific expression patterns
      for several antigens, which may reflect developmental immaturity rather than
      specific differentiation pathways.

PMID- 15722788
TI  - Correlation of HER2 gene amplification with expression of the apoptosis
      suppressing genes bcl-2 and bcl-x-L in ductal carcinoma in situ of the breast.
AB  - The protein product of the HER2 oncogene is overexpressed in an estimated 25 to
      30% of breast carcinomas and is considered an indicator of poor clinical outcome.
      The bcl-2 and the bcl-x-L genes are the 2 main genes of the bcl-2 gene family
      that suppress tumor cell death/apoptosis. HER2 gene amplification is also
      described in a percentage of cases of ductal carcinoma in situ (DCIS) of the
      breast. However, the relationship of such overexpression with the apoptosis
      suppressing genes is currently unknown. A total of 37 consecutive cases of DCIS
      were immunostained for HER2 overexpression (clone CB11, Ventana), and expression
      of bcl-2 and bcl-x-L. DCIS cases were graded using the criteria of Holland et al.
      HER2 overexpression was scored 0 to 3+; 0 and 1+ were considered negative
      staining and 2+ and 3+ were considered positive staining. HER2 gene amplification
      was also confirmed with fluorescent in situ hybridization (FISH). HER2 was
      positive in 22 of the 37 DCIS cases (60%) in accordance with previous reports.
      Immunohistochemical overexpression of HER2 was also highly correlated with HER2
      amplification by FISH. HER2 overexpression (confirmed by FISH) was mostly seen in
      grade II (9 of 17) and grade III (9 of 12) DCIS lesions. Only 1 of the HER2
      amplified cases was a grade I lesion. Furthermore, HER2 overexpression correlated
      with the presence of necrosis (P=0.003). Similarly, of the cases overexpressing
      HER2 at the highest level (3+), 90% were grade II or grade III lesions. A total
      of 73% of these cases also exhibited necrosis. Overexpression of HER2 3+ was also
      highly correlated with the presence of the apoptosis-suppressing gene bcl-x-L
      (coexpression in 87% of cases, P=0.01) but not with the prototype apoptosis
      suppressing gene bcl-2 (coexpression in 50% of cases, P value not significant).
      First, in DCIS overexpression of HER2 the majority of grade II and grade III
      lesions is seen, and this correlates with the presence of necrosis. Second, HER2
      overexpression is also highly correlated with the expression of the apoptosis
      suppressing gene bcl-x-L, but not with the prototype apoptosis-suppressing gene
      bcl-2. These differences may prove useful in defining groups of DCIS lesions with
      enhanced tumor cell growth and propensity for progression to invasion.

PMID- 15722787
TI  - Safety and biologic activity of intravenous BCL-2 antisense oligonucleotide
      (G3139) and taxane chemotherapy in patients with advanced cancer.
AB  - G3139 is a BCL-2 antisense oligonucleotide whose antitumor effects in preclinical
      models are enhanced when combined with taxane-based chemotherapy. This trial
      determined the safety and biologic activity of G3139 given with paclitaxel and
      docetaxel for the treatment of progressive solid tumors. Three cohorts of
      patients received weekly paclitaxel 100 mg/m2 on days 1, 8, and 15 concurrently
      with a 21-day continuous infusion of G3139 at 4.1, 5.3, and 6.9 mg/kg/d,
      depending on the cohort. Two subsequent cohorts received docetaxel (75 mg/m2) on
      day 5 of a 5-day infusion of G3139 at 5 or 7 mg/kg/d. Bcl-2 protein levels in
      peripheral blood mononuclear cells (PBMCs) were assayed on an exploratory basis.
      Fifteen patients were treated. Eight received a total of 14 cycles of G3139 and
      paclitaxel; seven received a total of 22 cycles of G3139 and docetaxel. Eight
      patients required dose modifications for either grade 4 neutropenia (6 patients)
      or grade 1-2 reversible transaminitis (2 patients). No radiographic responses
      were seen, although two of the six taxane-naive prostate cancer patients
      exhibited a prostate-specific antigen decline greater than 50%. Bcl-2 protein
      levels in PBMCs declined with treatment as assessed by immunohistochemistry. The
      authors conclude that G3139, whether given as a 5- or 21-day infusion, is well
      tolerated with taxane chemotherapy and is biologically active by
      immunohistochemistry at doses up to and including 7 mg/kg/d, using weekly
      paclitaxel (100 mg/m2) or docetaxel every 3 weeks (75 mg/m2). These data support
      the dose selection of ongoing phase 2 studies of G3139 at 7 mg/kg/d and docetaxel
      75 mg/m2.

PMID- 15722789
TI  - Estrogen receptor beta in breast cancer: associations between ERbeta, hormonal
      receptors, and other prognostic biomarkers.
AB  - The estrogen receptor (ER)-beta isoform has been recently identified to be
      distinct from ERalpha isoform and regulates separate sets of genes, and can exert
      opposite signaling functions depending on the ligand and response elements.
      Previous studies of ERbeta have been at the mRNA level and few by
      immunohistochemistry, and the results are inconsistent. In this study the authors
      compared expression of ERbeta with those of other prognostic biomarkers by
      immunohistochemistry on tissue microarray slides, and with morphologic parameters
      on 147 cases of primary breast cancer. Immunoreactivity of more than 10% of
      cancer cells was considered to be positive. Associations between categoric
      variables were analyzed using the chi test, and a P value less than 0.05 was
      considered to be significant. ERbeta was expressed in benign epithelium and
      stromal cells, and breast cancer cells in 59% of different histologic types of
      breast cancer. ERbeta was coexpressed with ERalpha in 45% of cases. There was a
      statistically significant association between expression of ERbeta and Her-2/neu
      (P<0.000), cathepsin D (P<0.02), p53 (P<0.03), and PS2 (P<0.002). Ki-67 was
      almost exclusively expressed in ERbeta-positive cells. No statistically
      significant association was seen between ERbeta expression and histologic grade,
      DNA ploidy, or S-phase.

PMID- 15722790
TI  - Androgen receptor expression in ductal carcinoma in situ of the breast: not a
      helpful marker for classification such as estrogen receptor alpha and
      progesterone receptor.
AB  - Androgen receptor (AR) is known to be expressed in approximately 70 to 90% of
      invasive breast cancers, but there are still conflicting data in terms of AR
      expression in ductal carcinoma in situ (DCIS). The aim of this study was to
      evaluate AR expression in DCIS and to compare these results with nuclear grading
      and with other common endocrine-related markers. On this basis the authors
      performed immunohistochemical staining for estrogen receptor (ER)-alpha and ER
      beta, progesterone receptor (PR), pS2, her-2/neu, and AR in 59 cases of DCIS (24
      low grade, 5 intermediate grade, 30 high grade). They found a strong correlation
      of expression of ER-alpha (P=0.003), PR (P<0.0001), and nuclear grading. For AR
      expression, 44.1% of all DCIS were positive, but there was no correlation between
      nuclear grading (P=0.535) and the expression of the other factors. The authors
      conclude that AR expression in DCIS is not correlated with nuclear grading and
      with the expression of other known endocrine-related markers such as ER-alpha and
      -beta, PR, pS2, and her-2/neu. The immunohistochemical assessment of AR status,
      therefore, may not help in providing a more objective way of classifying DCIS.

PMID- 15722791
TI  - Mammary ducts with and without focal myoepithelial cell layer disruptions show a
      different frequency of white blood cell infiltration and growth pattern:
      implications for tumor progression and invasion.
AB  - The authors' previous studies revealed that a subset of ductal carcinoma in situ
      (DCIS) contained focally disrupted myoepithelial (ME) cell layers and basement
      membrane (BM). As the disruption of these two structures is a prerequisite for
      tumor invasion, and white blood cells (WBCs) contain digestive enzymes capable of
      degrading both the BM and damaged host cells, this study was designed to assess
      the possible roles of WBC in ME cell layer disruptions and tumor invasion. A
      total of 23 DCIS containing ducts with focally disrupted ME cell layers were
      selected from 94 such cases identified in the authors' previous studies. Two
      consecutive sections from each case were double immunostained, one with leukocyte
      common antigen (LCA) plus smooth muscle actin (SMA) and the other with Ki-67 plus
      SMA. Ducts lined by at least 50 epithelial cells and distinct ME cell layers were
      examined. A total of 191 duct cross-sections were found to contain focal ME cell
      layer disruptions; of these, 186 (97.4%) were with and 5 (2.6%) were without WBC
      infiltration. Of 207 morphologically similar sections without ME disruptions, 46
      (22.2%) were with and 161 (77.8%) were without WBC infiltration. Ki-67-positive
      cells in ducts with focally disrupted ME cell layers were generally subjacent to
      ME cell layers, and more than 30 clusters of multiple proliferating cells were
      seen directly overlying or near focally disrupted ME cell layers. In contrast, Ki
      67-positive cells in ducts without ME disruptions were scattered over the entire
      epithelial compartment. The significantly different frequency of WBC infiltration
      and clusters of multiple proliferating cells in ducts with and without ME
      disruptions suggests that WBCs might play important roles in ME disruption and
      tumor invasion.

PMID- 15722792
TI  - The clinical significance of p53, p21, and p27 expressions in rectal carcinoma.
AB  - Many checkpoint proteins that are involved in the control of the cell cycle and
      apoptosis have been investigated, but only a few studies have evaluated the
      prognostic significance of multiple factors only in rectal carcinomas. The aim of
      this study was to determine the role of p53, p21, and p27 protein expression as a
      prognostic factor in rectal carcinomas. Formalin-fixed, paraffin-embedded tissue
      blocks from 45 rectal adenocarcinomas with appropriate clinical and prognostic
      data were examined. The standard streptavidin-biotin immunoperoxidase method was
      used for immunostaining with p53 protein, p21 WAF1/Cip1 protein, and p27 Kip1
      protein. The extent of positive p53, p21, and p27 staining was graded
      semiquantitatively. The clinicopathologic and prognostic features were
      statistically analyzed. No significant association was found between p53 status
      and p21 or p27 protein expression (chi2 test, P=0.42 and P=0.18 respectively).
      There was no correlation between the expressions of p53, p21, and p27, and
      conventional clinicopathologic features. The mean time interval to recurrence was
      25.7+/-24.7 months (range, 0-54 months). p53, p21, and p27 expression was not
      associated significantly with recurrence and distant metastasis. However, a
      significant relationship was found between the expression of p27 protein and
      hepatic metastasis (independent samples t-test, P=0.007). The authors concluded
      that p53, p27, and p21 protein expression was not related to the
      clinicopathologic parameters, tumor aggressiveness, metastatic potential, and
      survival in rectal carcinomas. Further studies are needed to evaluate the
      predictors of outcome in rectal cancer, considering a variety of prognosticators.

PMID- 15722793
TI  - Prognostic significance of DCC and p27Kip1 in colorectal cancer.
AB  - The progression of colorectal cancer is a multistage process associated with
      specific molecular alterations. The stepwise accumulation of these multiple
      genetic mutations progressively results in the acquisition of neoplastic cell
      behavior. The genetic abnormalities associated with the expression of metastatic
      phenotype, therefore, may be of prognostic significance in the clinical treatment
      of colorectal cancer patients. In this study, the immunohistochemical expression
      of the deleted in colorectal cancer gene (DCC) and p27Kip1 was assessed in 168
      paraffin-embedded, formalin-fixed tumors of patients with stage II and III
      colorectal cancer. Kaplan-Meier survival curves and log-rank statistics were used
      to analyze survival times after curative primary tumor resection, and Cox
      proportional hazards models were used to adjust the assessment of demographic and
      clinical covariates. Loss of DCC or p27Kip1 expression had no influence on
      survival in patients with stage II or III colorectal cancer. The 5-year survival
      rates of DCC-positive and DCC-negative tumors were 51.8% and 35.7% (P=0.40),
      respectively. The 5-year survival rate of patients with p27Kip1-positive tumors
      was 47.9%, whereas the rate for patients with p27Kip1-negative tumors was 38.8%
      (P=0.68). After adjustment for all evaluated variables, neither DCC or p27Kip1
      was found to be a predictor of survival (risk ratio for DCC, 0.98; 95% confidence
      interval, 0.66-1.56; P=0.92; risk ratio for p27Kip1, 0.87; 95% confidence
      interval, 0.58-1.29; P=0.49). The present study demonstrated that the expression
      of neither DCC nor p27Kip1 was predictive in poor survival outcome in patients
      with stage II or III colorectal cancer.

PMID- 15722794
TI  - CDX2 immunostaining as a gastrointestinal marker: expression in lung carcinomas
      is a potential pitfall.
AB  - Paraffin-embedded sections of various adenocarcinomas (13 colonic, 11 mucinous
      ovarian, 5 serous ovarian, 8 pancreatic, 6 ampullary, 12 gastric, 5 esophageal,
      10 endometrial, 29 breast, and 55 lung) and 29 additional lung carcinomas
      (nonadenocarcinomas) were immunostained with antibodies to CDX2 protein,
      cytokeratin 7 (CK7), and cytokeratin 20 (CK20). The 84 lung carcinomas were also
      stained with antibody to thyroid transcription factor-1 (TTF-1). All colorectal
      and most ovarian mucinous carcinomas were strongly and diffusely immunoreactive
      for CDX2. Esophageal, gastric, and ampullary adenocarcinomas showed variable
      immunoreactivity for CDX2. All breast, nonmucinous ovarian, and most endometrial
      and pancreatic adenocarcinomas showed no immunoreactivity for CDX2. CK7 and CK20
      expression was similar to previous reports. Ten of 84 primary lung carcinomas
      (12%) were immunoreactive for CDX2 expression. Of these, 5 (4 adenocarcinomas and
      1 large cell carcinoma) were reactive for TTF-1. Gene expression profiling data-
      available for 32 of these 84 tumors--showed CDX2 gene expression in 7 of 8 (88%)
      CDX2 immunoreactive tumors whereas only 1 of 24 (4%) tumors negative for CDX2
      immunoreactivity showed CDX2 gene expression. The authors conclude that CDX2 is a
      relatively specific marker for tumors with intestinal differentiation, with the
      caveat that its expression can be seen in primary large cell and adenocarcinomas
      of the lung and mucinous carcinomas of the ovary.

PMID- 15722795
TI  - Detection of KSHV in transbronchial biopsies in patients with Kaposi sarcoma.
AB  - In transbronchial biopsies, Kaposi sarcoma (KS) is difficult to correctly
      diagnose by H&E staining due to the inherent vascular nature of the lung tissue,
      coupled with the subtle nature of the changes in early KS. Since KS-associated
      herpesvirus (KSHV) has been found in all clinical forms of KS, the detection of
      KSHV genomic DNA sequences and/or viral products may be helpful in the diagnosis
      of pulmonary KS. From their files during the past 10 years, the authors
      identified ten HIV/AIDS patients who were positive for KS in transbronchial
      biopsies and four HIV/AIDS patients with KS-negative transbronchial biopsies.
      Immunohistochemistry with antibodies against the latency-associated nuclear
      antigen (LANA-1 or LNA) of KSHV was performed. Nested polymerase chain reactions
      (PCR) with KSHV ORF-K1 or -K9 were performed in all cases, and the KSHV sequences
      were detected in 9/10 (90%) KS cases. Immunohistochemical analysis was able to
      detect 4/10 (40%) cases. One case was negative by both PCR and
      immunohistochemistry. Of the five KS cases that were not diagnosed definitively
      ("consistent with" or "suspicious for"), two were confirmed by both
      immunoreactivity and PCR. One of the negative control cases was positive for KSHV
      by PCR but not by immunohistochemistry. The patient was thereafter found to have
      a clinical history of pulmonary KS at another hospital. In conclusion, in
      transbronchial biopsies of the lung suspicious for KS, PCR is the most sensitive
      technique available for clinical diagnosis of KS. Immunohistochemistry analysis
      might be helpful in difficult pulmonary KS cases.

PMID- 15722797
TI  - Comparison of monoclonal versus polyclonal calretinin antibodies for
      immunohistochemical diagnosis of malignant mesothelioma.
AB  - Of putative specific markers for diffuse malignant mesothelioma, nuclear staining
      with Zymed polyclonal calretinin antibody has shown the best specificity to date
      for epithelial diffuse malignant mesothelioma versus adenocarcinoma. We compared
      specificity and sensitivity of this polyclonal antibody for diagnosis of diffuse
      malignant mesothelioma with a new monoclonal antibody from DAKO. One hundred
      eighteen adenocarcinomas and 111 diffuse malignant mesotheliomas-70 epithelial,
      22 sarcomatous, and 19 biphasic-were immunostained with calretinin antibodies
      from Zymed (polyclonal rabbit, prediluted, PAD:DC8) and DAKO(monoclonal mouse,
      1:100, clone DAK Calret 1) using manufacturer-recommended procedures. Cases were
      blinded and assessed for nuclear versus cytoplasmic staining, percent positive
      cells, and background. Both antibodies showed similar positive predictive values
      for diffuse malignant mesothelioma by nuclear staining (Zymed=95%; DAKO=97%).
      False positives in 4 (3.4%) and 2 (1.7%) adenocarcinomas, respectively, stained
      greater than 10% of cells. Sensitivity for epithelial malignant mesothelioma was
      slightly less for DAKO antibody (Zymed=80%; DAKO=73%). Neither antibody performed
      well on sarcomatous malignant mesothelioma (Zymed=2/22; DAKO=1/22). Both
      antibodies are useful in the diagnosis of epithelial malignant mesothelioma,
      although monoclonal antibody is slightly less sensitive.

PMID- 15722796
TI  - The expression of the SWI/SNF ATPase subunits BRG1 and BRM in normal human
      tissues.
AB  - SWI/SNF is a chromatin-remodeling complex important in gene regulation, cytokine
      responses, tumorigenesis, differentiation, and development. As a multitude of
      signaling pathways require SWI/SNF, loss of SWI/SNF function is expected to have
      an impact on cellular phenotypes. The SWI/SNF ATPase subunits, BRG1 and BRM, have
      been shown to be lost in a subset of human cancer cell lines and human primary
      cancers and may represent tumor suppressor proteins. To better understand the
      biology of these proteins, the authors examined the expression pattern of BRG1
      and BRM in a variety of normal tissues. BRG1 expression was predominantly seen in
      cell types that constantly undergo proliferation or self-renewal; in contrast,
      BRM was preferentially expressed in brain, liver, fibromuscular stroma, and
      endothelial cell types, cell types not constantly engaged in proliferation or
      self-renewal. This differential expression suggests that these proteins serve
      distinct functions in human tissues.

PMID- 15722798
TI  - A novel method for making "tissue" microarrays from small numbers of suspension
      cells.
AB  - Tissue microarrays (TMAs) are a highly efficient method for large-scale protein
      expression studies. To date most TMAs have been constructed using paraffin
      embedded specimens. The authors developed a method that allows construction of
      TMAs from small numbers of cells in suspension. Spun pellets of 1x10 to 1x10
      cells are directly processed and embedded in paraffin in an Eppendorf tube.
      Cylindrical cores of 0.6 mm are taken from these tubes and embedded in a
      recipient paraffin block to create a TMA. This relatively simple but versatile
      method enables very small numbers of cells in suspension to be analyzed using the
      TMA technology and allows for the study of hematolymphoid and related disorders
      of the blood and bone marrow for which solid tissue samples cannot be readily
      obtained. With the increasing trend toward obtaining small samples for screening
      and diagnostic purposes, this method provides a means to manipulate small volume
      samples for high-throughput immunohistochemical analysis. This method is also
      amenable for use for cultured cells.

PMID- 15722799
TI  - Cell culture block array for immunocytochemical study of protein expression in
      cultured cells.
AB  - Immunocytochemical staining of cultured cells using specific antibodies is a
      powerful technique to study the expression and subcellular localization of
      proteins. However, this technique is associated with sample-to-sample variations
      because samples are handled individually and manually. Cell permeation is needed
      when intracytoplasmic or nuclear proteins are studied. Storage of cultured cells
      is difficult, and experiments must be repeated if additional studies are desired
      later, which introduces more variations. We developed a cell culture block array
      technique that converts cultured cells into a permanently fixed form identical to
      tissue sections prepared for pathologic examination. Cells from different
      cultures can be embedded in a single block. Many identical sections, each
      containing cells from multiple cultures, may be stained with different antibodies
      using an automated stainer. As a result, sample-to-sample variation is
      eliminated. Because cells in these blocks are sectioned by knives, all cellular
      proteins come into direct contact with antibodies, and cell permeation is not
      needed. Such blocks can be conveniently stored for years without loss of
      antigens, providing a constant source for future studies. We demonstrated the
      utility of this technique by studying the proliferation and neuroendocrine
      differentiation of prostate cancer-derived LNCaP cells cultured in vitro.

PMID- 15722800
TI  - Development of new rabbit monoclonal antibody to estrogen receptor:
      immunohistochemical assessment on formalin-fixed, paraffin-embedded tissue
      sections.
AB  - Evaluation of estrogen and progesterone receptors in breast cancer is widely used
      for the prediction of the response to endocrine therapy and as a biologic
      parameter closely related to disease prognosis. Immunohistochemistry is
      considered a specific, sensitive, and economic method for the determination of
      estrogen receptor/progesterone receptor status. The authors developed the first
      rabbit antiestrogen receptor monoclonal antibody (clone SP1) used in
      immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections
      especially from breast carcinomas. This new antibody, compared with currently
      available antiestrogen receptor antibodies, has important advantages, including
      its reactivity even without heat-based antigen retrieval of fixed, embedded
      tissue sections in immunohistochemistry, and the predominance of nuclear
      immunostaining with only a very low cytoplasmic signal. A comparative study of
      immunohistochemistry on 61 histologic specimens from breast cancer cases showed
      that SP1 yields the same results as the well-known, standardized mouse monoclonal
      antibody to estrogen receptor (clone 1D5). Antibody affinity of SP1 is 8 times
      higher than that of 1D5. Thus, SP1 may prove of great value in the assessment of
      estrogen receptor status in human breast cancer.

PMID- 15722801
TI  - A simple inexpensive method for the production of tissue microarrays from needle
      biopsy specimens: examples with prostate cancer.
AB  - The use of tissue microarrays has become an efficient method for the high
      throughput analysis of tissues with molecular markers, yet these studies have not
      been used to leverage the limited materials present in needle biopsies of human
      tissues. The use of these biopsy tissues is crucial to study diseases in patients
      who are treated by nonsurgical methods such as radiation, chemotherapy, or
      palliative care. The authors present a simple, inexpensive method for using
      needle biopsy specimens in tissue microarrays. Using this process with prostate
      cancer specimens, the authors demonstrate that over 150 slides can be produced
      from a single area of cancer in a needle biopsy and that the length of the core
      involved by cancer in the needle biopsy determines the number of available tissue
      microarray slides. The authors also note the optimal number of samples (three)
      needed from a single patient biopsy to guarantee sufficient material for analysis
      and perform an immunohistochemical correlation between needle biopsy and surgical
      resection tissue microarray samples for the quantitative marker Ki-67. This
      process can be extended to any type of needle biopsy specimen, increasing the
      number of studies and potential use of these tissues as a practical reality.

PMID- 15722802
TI  - Metastasis of small cell carcinoma of lung into an ovarian mucinous neoplasm:
      immunohistochemistry as a useful ancillary technique for diagnosis and
      classification of rare tumors.
AB  - The authors report the first case of ovarian mucinous adenocarcinoma with
      metastasis from a synchronous small cell neuroendocrine carcinoma of the lung. A
      62-year-old white woman presented with weight loss and increased abdominal girth.
      She was found to have a large, complex cystic mass in the pelvis, and during the
      staging evaluation, a large, right pulmonary hilar mass was detected. Bronchial
      brushing as well as transbronchial fine-needle aspiration was diagnostic of small
      cell carcinoma. The patient received 3 cycles of chemotherapy with carboplatin
      and subsequently underwent a supracervical hysterectomy and bilateral salpingo
      oophorectomy. A large, multiloculated cystic mass was found arising from the
      right ovary. Microscopic examination disclosed a mucinous neoplasm with both
      mucinous cystadenoma and mucinous papillary adenocarcinoma components. A
      microscopic focus of cells with "atypical" cytomorphologic features was detected
      within the mucinous neoplasm. Immunohistochemistry showed that group of cells to
      be positive for thyroid transcription factor 1 and chromogranin, confirming them
      to be metastasis from the pulmonary small cell neuroendocrine carcinoma. This
      case, in addition to being the first reported case of such metastasis, also
      highlights the diagnostic utility of immunohistochemistry as a reliable and very
      useful ancillary technique for the diagnosis of neoplasms with unusual clinical
      and/or histomorphologic presentations. The clinical and prognostic implications
      are also discussed.

PMID- 15722803
TI  - The effects of cognitive-behavioral and physical therapy preventive interventions
      on pain-related sick leave: a randomized controlled trial.
AB  - OBJECTIVE: Recent recommendations suggest that reassuring patients with an acute
      bout of low back pain and encouraging a return to normal activities may be
      helpful in preventing the development of chronic disability. There is also a
      question as to whether psychologic or physical therapy interventions actually add
      anything to such reassurance and advice in terms of preventing chronicity. This
      study aimed to ascertain the preventive effects on future sick leave and health
      care utilization of adding on a cognitive-behavioral group intervention or a
      cognitive-behavioral group intervention and preventive physical therapy (focused
      on activity and exercise) relative to a minimal treatment group (examination,
      reassurance, and activity advice). SUBJECTS: A total of 185 patients seeking care
      for nonspecific back or neck pain who were employed and at risk for developing
      long-term disability volunteered to participate in the study. Of these 185, 158
      (85%) completed the pre- and 1-year follow-up assessments. RESULTS: Significant
      differences were observed on the key outcome variables of future health-care
      utilization and work absenteeism. For health-care utilization, the cognitive
      behavioral intervention group and preventive physical therapy group had
      significantly fewer healthcare visits than did the Minimal Treatment Group. For
      work absenteeism, the cognitive-behavioral intervention group and cognitive
      behavioral intervention and preventive physical therapy group had fewer days
      during the 12-month follow-up than did the Minimal Treatment Group. The risk for
      developing long-term sick disability leave was more than five-fold higher in the
      Minimal Group as compared with the other 2 groups. However, there was no
      difference between the cognitive-behavioral intervention group and cognitive
      behavioral intervention and preventive physical therapy group on sick leave.
      CONCLUSION: Taken as a whole, this study shows that adding cognitive-behavioral
      intervention and cognitive-behavioral intervention and preventive physical
      therapy can enhance the prevention of long-term disability. There was no
      substantial difference in the results between the cognitive-behavioral
      intervention group and cognitive-behavioral intervention and preventive physical
      therapy group.

PMID- 15722804
TI  - Sex differences in delayed onset muscle pain.
AB  - OBJECTIVE: In contrast to the research using typical experimental pain stimuli,
      there is no consensus that women are more sensitive to delayed onset muscle pain
      than men. The purpose of this study was to examine sex differences in delayed
      onset muscle pain with use of a quantified stimulus intensity and
      multidimensional and valid pain measures. METHODS: Ninety-five participants
      (49.5% women) completed eccentric exercise and then returned to the laboratory at
      24 and 48 hours postexercise. The same relative intensity of the eccentric
      exercise was administered to women and men based on their eccentric strength.
      RESULTS: The occurrence of muscle pain was confirmed by increases in intensity,
      F2, 182 = 162.28, P<0.01, eta = 0.64, and unpleasantness, F2, 182 = 204.03, P <
      0.01, eta = 0.69, and standardized pain ratings, F2, 180 = 67.44, P < 0.01, eta =
      0.43. The affective ratios indicated that the muscle pain was more unpleasant
      than intense. No sex differences were detected except that men reported higher
      affective ratios than women, F1, 92 = 4.06, P < 0.05, eta = 0.04. DISCUSSION: The
      absence of higher muscle pain ratings in women than men in this investigation
      resembles a review of the delayed onset muscle soreness and pain literature.
      However, the findings contradict a few other acute muscle pain investigations, in
      which actual muscle tissue damage was not induced by eccentric contractions.
      Additional research is required to identify the parameters that influence the
      detection of sex differences.

PMID- 15722805
TI  - Differential effects of neuropathic analgesics on wind-up-like pain and
      somatosensory function in healthy volunteers.
AB  - OBJECTIVES: To investigate the effects of gabapentin, carbamazepine, and
      amitriptyline on temporal summation, simple nociceptive pain, and innocuous touch
      sensation in healthy volunteers. METHODS: A placebo controlled four-way crossover
      double-blind randomized protocol was followed. Seventeen healthy subjects, male
      and female, aged 18 to 24, took part. Punctate pain, temporal summation pain to
      repeat punctate stimulation, and vibration detection threshold were assessed in
      triplicate. Study drugs were given as bedtime and early morning doses with
      assessments carried out midmorning. RESULTS: Gabapentin and carbamazepine
      significantly reduced the intensity of temporal summation pain (P < 0.001 and P <
      0.01 respectively), whereas amitriptyline significantly increased temporal
      summation pain (P < 0.001). None of the drugs affected pain produced by a single
      punctate stimulus (P > 0.05). Carbamazepine increased vibration detection
      thresholds (P < 0.05), but neither gabapentin nor amitriptyline had any
      detectable effect on vibration. DISCUSSION: We have shown that gabapentin,
      carbamazepine, and amitriptyline, three pharmacologically different drugs, have
      distinct and quantifiable effects on somatosensory pathways in healthy
      volunteers. These findings provide a link between pharmacology of the study drugs
      and clinical effectiveness. The effects of gabapentin and carbamazepine on
      temporal summation pain show that these drugs can block centrally amplified wind
      up pain in the absence of a neuropathic disorder.

PMID- 15722806
TI  - Parents' views about infant pain in neonatal intensive care.
AB  - OBJECTIVE: The purpose of this study was to describe parents' perceptions and
      feelings about their infant's pain experience and pain care in the neonatal
      intensive care unit. METHOD: Thematic content analysis was used to encode the
      qualitative information contained in parents' written comments on a questionnaire
      about their views on infant pain and pain care. The questionnaire was completed
      by 257 parents from 9 neonatal units in the United Kingdom (n = 196) and 2
      neonatal units in the United States (n = 61). RESULTS: Parents' comments
      indicated that they saw medical procedures as the major source of their infant's
      pain, wanted more information, and generally desired more involvement in this
      aspect of their infant's care. Parents' comments indicated that their infant's
      pain affected them emotionally and that they worried about their future
      relationship with their infant. Parents also articulated specific ways in which
      health care professionals could assist them and their infants in coping with
      neonatal intensive care unit-related pain. DISCUSSION: The findings from this
      study expand knowledge about how parents understand and respond to the difficult
      situation in which their newborn infant is subjected to essential but painful
      procedures. The findings provide direction for research and clinical practice
      interventions aimed at: 1) helping parents to gain knowledge and correct their
      misperceptions; 2) engaging parents in meaningful dialog about their concerns and
      preferences for involvement; and 3) helping parents to develop effective coping
      strategies to reduce psychologic distress related to their infant's pain.

PMID- 15722807
TI  - Global and specific behavioral measures of pain in children with cerebral palsy.
AB  - OBJECTIVES: The aim of this research was to validate global and behavioral
      observation methods for measuring pain in children with cerebral palsy (CP).
      MATERIALS AND METHODS: Nineteen children diagnosed with CP (2-21 years of age)
      and their primary caregivers participated in this study. Children and their
      caregivers were videotaped in their home before, during, and after a stretching
      exercise, and tests of cognitive and social development were administered.
      Children who were able to pass a training task were also asked to rate their
      experience of pain using a numerical rating scale (self-report NRS), but only 5
      children (24%) passed so their self-report scores were not included. Healthcare
      professionals rated videotaped segments for each of the 3 time periods in a
      randomized order using an observer NRS and the Non-Communicating Children's Pain
      Checklist-Postoperative Version (NCCPC-PV). Raters trained in the Child Facial
      Coding System (CFCS) examined the same videotaped segments. RESULTS: Results
      showed significantly greater pain behavior (observer NRS, NCCP- PV) during the
      stretching procedure than during the baseline and recovery segments. There were
      no significant differences in CFCS scores, across time segments. CONCLUSIONS:
      These findings support the hypothesis that children with CP express discernible
      pain behaviors regardless of cognitive or language ability. These results
      contribute to multidimensional assessment of pain in children with neurologic
      impairment.

PMID- 15722808
TI  - Prevalence of clinical hypertension in patients with chronic pain compared to
      nonpain general medical patients.
AB  - OBJECTIVES: In healthy individuals, elevated blood pressure is associated with
      diminished acute pain sensitivity. These cardiovascular/pain regulatory system
      interactions appear altered in patients with chronic pain; elevated blood
      pressure is associated with increased acute and chronic pain responsiveness. If
      these alterations reflect failure of overlapping systems modulating pain and
      blood pressure, it was expected that prevalence of clinical hypertension would be
      increased in the chronic pain population. METHODS: A retrospective review was
      conducted on randomly selected records of 300 patients with chronic pain (Pain)
      evaluated at a tertiary care pain center and 300 nonpain internal medicine
      (Medicine) patients seen at the same institution. RESULTS: Results revealed that
      39% of the Pain group was diagnosed with clinical hypertension, compared with 21%
      of the Medicine group (P < 0.001). Analyses by sex revealed similar group
      differences in males (P < 0.05) and females (P < 0.001), although the difference
      in females was double in magnitude compared with males. In contrast to more
      frequent male hypertension in the general population and the Medicine sample,
      females were more often diagnosed with hypertension (41.2%) than males (35.6%) in
      the Pain group. Similar group differences were obtained for antihypertensive use
      (P < 0.001). Stepwise logistic regression in the Pain group revealed that chronic
      pain intensity was a significant predictor of hypertensive status independent of
      the effects of age, race/ethnicity, and parental hypertension (P < 0.05).
      DISCUSSION: These results suggest that chronic pain may be associated with
      increased risk of hypertension. Factors that may underlie this association are
      discussed.

PMID- 15722809
TI  - Patterns of pain variation related to myogenous temporomandibular disorders.
AB  - OBJECTIVES: Myogenous temporomandibular disorders are characterized by jaw muscle
      pain. The aims were: 1) to characterize this pain generally in terms of
      intensity, frequency, duration, and behavior across a period of 2 weeks; 2) to
      identify main intraday pain patterns and to examine whether subgroups of patients
      in this respect differed in clinical, demographic, pain and sleep variables,
      psychosocial factors, and use of medication; and 3) to investigate some possible
      interday trends of pain intensity at a group level. METHOD: One hundred thirty
      three patients with myogenous temporomandibular disorders completed a 2-week
      diary, rating pain intensity (100 mm Visual Analog Scale [VAS]), duration,
      behavior (verbal 6-point scale), and medication use on 4 times of the day.
      Furthermore, questionnaires were completed to score pain period before seeking
      treatment, spread of pain, and demographic, psychosocial, and sleep variables.
      RESULTS: In the diary, pain intensity, frequency, daily pain duration, and the
      score of pain behavior were on average 29.1 mm, 69% of the scoring times, 5.5
      hours, and 1.8 points (approaching "pain present, but I can ignore it at times"),
      respectively. Pain intensity was, on average, maximal late in the day (before
      dinner or bedtime) for the majority of patients (79%) and early in the day
      (before breakfast or lunchtime) for the minority (21%). The larger subgroup had a
      significantly higher daily pain intensity, more frequently a widespread pain and
      problems with falling asleep at bedtime, agreed more about the role of a
      physician as an external health locus of control, and had a more distancing
      coping style. Both subgroups were similar for other variables, most notably in
      the level of state anxiety and depressive mood, and in a sparse use (7.8% of all
      possible times) of over-the-counter medication. Daily mean VAS scores, averaged
      across patients, were approximately constant for the various diary days. Both the
      daily mean and maximal VAS score were not related to a specific day of the week.
      CONCLUSIONS: Two main daily pain patterns occur in patients with myogenous
      temporomandibular disorders (79%: maximal pain late in the day; 21%: early in the
      day), which might be related to differences in processes that influence pain
      sensitivity and patterns of jaw muscle activation. The interday similarities in
      pain level suggest that a sustained influence of counseling after the intake or
      an influence of a common behavioral pattern with a cycle duration of a week are
      not involved.

PMID- 15722810
TI  - The effectiveness of multidisciplinary rehabilitation in the treatment of
      fibromyalgia: a randomized controlled trial.
AB  - OBJECTIVES: To assess the effectiveness of multidisciplinary rehabilitation in
      the treatment of fibromyalgia in comparison to standard medical care. METHODS:
      Seventy-nine men and women were randomly assigned to one of two groups. The
      intervention group consisted of a rheumatologist and physical therapist intake
      and discharge, 18 group supervised exercise therapy sessions, 2 group pain and
      stress management lectures, 1 group education lecture, 1 group dietary lecture,
      and 2 massage therapy sessions. The control group consisted of standard medical
      care with the patients' family physician. Outcome measures included self
      perceived health status, pain-related disability, average pain intensity,
      depressed mood, days in pain, hours in pain, prescription and nonprescription
      medication usage, and work status. Outcomes were measured at the end of the 6
      week intervention and at 15-month follow-up. RESULTS: Thirty-five out of 43
      patients from the intervention group and 36 out of 36 patients from the control
      group completed the study. There were no statistically significant differences
      between the 2 groups prior to intervention. Intention-to-treat analysis revealed
      that the intervention group, in comparison to the control group, experienced
      statistically significant changes at intervention completion in self-perceived
      health status, average pain intensity, pain related disability, depressed mood,
      days in pain, and hours in pain, but no significant differences in
      nonprescription drug use, prescription drug use, or work status. At 15 months,
      all health outcomes retained their significance except health status.
      Nonprescription and prescription drug use demonstrated significant reductions at
      15 months. Binary logistic regression indicated that long-term changes in Pain
      Disability Index were influenced by long-term exercise adherence and income
      status. CONCLUSIONS: Positive health-related outcomes in this mostly unresponsive
      condition can be obtained with a low-cost, group multidisciplinary intervention
      in a community-based, nonclinical setting.

PMID- 15722811
TI  - Widespread sensory hypersensitivity is a feature of chronic whiplash-associated
      disorder but not chronic idiopathic neck pain.
AB  - OBJECTIVES: To investigate sensory changes present in patients with chronic
      whiplash-associated disorders and chronic idiopathic neck pain using a variety of
      quantitative sensory tests to better understand the pain processing mechanisms
      underlying persistent symptoms. METHODS: A case control study was used with 29
      subjects with chronic whiplash-associated disorders, 20 subjects with chronic
      idiopathic neck pain, and 20 pain-free volunteers. Pressure pain thresholds were
      measured over the articular pillars of C2-C3, C5-C6, the median, radial, and
      ulnar nerve trunks in the arm and over a remote site, the muscle belly of
      tibialis anterior. Heat pain thresholds, cold pain thresholds, and von Frey hair
      sensibility were measured over the cervical spine, tibialis anterior, and deltoid
      insertion. Anxiety was measured with the Short-Form of the Spielberger State
      Anxiety Inventory. RESULTS: Pressure pain thresholds were decreased over cervical
      spine sites in both subject groups when compared with controls (P < 0.05). In the
      chronic whiplash-associated disorders group, pressure pain thresholds were also
      decreased over the tibialis anterior, median, and radial nerve trunks (P <
      0.001). Heat pain thresholds were decreased and cold pain thresholds increased at
      all sites (P < 0.03). No differences in heat pain thresholds or cold pain
      thresholds were evident in the idiopathic neck pain group at any site compared
      with the control group (P > 0.27). No abnormalities in von Frey hair sensibility
      were evident in either neck pain group (P > 0.28). DISCUSSION: Both chronic
      whiplash-associated disorders and idiopathic neck pain groups were characterized
      by mechanical hyperalgesia over the cervical spine. Whiplash subjects showed
      additional widespread hypersensitivity to mechanical pressure and thermal
      stimuli, which was independent of state anxiety and may represent changes in
      central pain processing mechanisms. This may have implications for future
      treatment approaches.

PMID- 15722812
TI  - Injections of botulinum toxin type a produce pain alleviation in intractable
      trigeminal neuralgia.
AB  - To report the effects of local injections of botulinum toxin type A regarding
      pain relief and long-term control in a patient with intractable trigeminal
      neuralgia. The patient was a 75-year-old man with trigeminal neuralgia in the
      left hemifacial region. His pain was unbearable and could not be controlled by
      carbamazepine, amitriptyline, or blocked by infiltration of a glycerol solution
      or phenol. The authors evaluated pain intensity, quality, and location using a
      Visual Analog Scale to establish the efficacy of botulinum toxin type A
      injections. Two units of botulinum toxin type A (Botox) were subcutaneously
      injected once in eight points distributed along the territory of V1 and V2.
      Visual Analog Scores were measured at baseline and at 7, 30, 60, and 90 days
      after treatment. The authors also examined the patient's general condition and
      daily life activities. The Visual Analog values were, respectively, 82, 54, 25,
      25, and 45 mm at each follow-up examination. No side effects were observed on the
      site of injection and on the patient's clinical state. The authors have been able
      to reduce trigeminal neuralgia pain with botulinum toxin type A injections in the
      V1, V2 territory during all the period of study, as well as to withdraw all
      medication. Interestingly, there was concomitant reduction of pain also in V3,
      which was not injected.

PMID- 15722813
TI  - The fasciitis-panniculitis syndrome presenting as complex regional pain syndrome
      type 1: report of a case.
AB  - A 28-year-old man presented with a clinical picture suggestive of complex
      regional pain syndrome type I following a blow to the thenar eminence and thumb.
      Symptoms, including swelling of the hand and distal forearm, progressed until an
      amputation was carried out to rid the patient of an unendurable painful and
      nonfunctioning wrist and hand. The histologic evaluation of the amputation
      specimen showed: 1) dermal edema, perivascular dermatitis, and epidermal
      hyperkeratosis; 2) subcutaneous chronic inflammation with subtotal replacement of
      the adipose lobules by fibrous tissue associated with thickening of the muscular
      fascia, implying the fasciitis-panniculitis reaction pattern; 3) atrophy,
      degeneration, necrosis, and focal calcifications of the skeletal muscles; 4)
      phlebosclerosis, phlebectasias and lymphocytic arteritis; and 5) increased
      cortical porosity of the bones. It seems that the pathogenetic process underlying
      the fasciitis-panniculitis syndrome may rarely manifest as a complex regional
      pain syndrome-like disorder.

PMID- 15722814
TI  - Analgesic effects of topical methadone: a report of four cases.
AB  - Topical morphine has been used on open wounds for pain management, but has a
      variable duration of action not suitable for palliative dressing changes. The
      objective of this study is to find an opioid and delivery method that would
      provide long-lasting pain relief between dressing changes. Methadone powder (100
      mg) was mixed in Stomahesive powder (10 g) and sprinkled on the open wound once
      daily at the time of dressing change. Four cases are presented with varying
      results using the methadone/Stomahesive mixture. Exudative wounds with exposed
      tissue work best, whereas dry wounds with eschar show less response. Topical
      methadone powder can be effective for pain relief in open, exudative wounds with
      little eschar. Further research questions are raised.

PMID- 15722815
TI  - Continuous intrathecal meperidine for severe refractory cancer pain: a case
      report.
AB  - The control of severe cancer pain may be problematic despite advances in pain
      management. Patients with severe intractable pain and/or intractable side effects
      may require aggressive interventional pain management strategies including the
      administration of medications by the continuous intrathecal route and/or
      neurosurgical procedures. Various medications, including opioids, local
      anesthetics, and alpha-2 agonists may be used intrathecally for the control of
      cancer pain. Failure of the intrathecal route may require the additional use of
      neurosurgical procedures such as cordotomy for pain control. We describe a case
      of severe cancer pain refractory to conventional intrathecal medications and
      cordotomy that was successfully managed by the addition of meperidine to the
      intrathecal regimen.

PMID- 15722816
TI  - 'Shine through' on dual tracer parathyroid scintigraphy: a potential pitfall in
      interpretation.
AB  - Dual tracer scintigraphy has become the procedure of choice for preoperative
      localization of parathyroid adenomas. The typical protocol used by most
      laboratories is to initially perform a Tc-99m sestamibi (MIBI) study with early
      and delayed (2-3 hours) washout phase images. This is followed by a thyroid
      specific Tc-99m pertechnetate study. A potential pitfall exists if the delayed
      phase of the initial MIBI study shows an intense, abnormal focus of retention.
      This focus may interfere with interpretation of the subsequent pertechnetate
      study because of a "shine through" effect. To differentiate a parathyroid adenoma
      from a thyroid adenoma, it may be necessary to repeat the thyroid-specific
      pertechnetate scan on a separate day after the dual tracer study.

PMID- 15722817
TI  - Heterogeneous patterns of lymphatic drainage to sentinel lymph nodes by primary
      melanoma from different anatomic sites.
AB  - We want to define the patterns of lymphatic drainage for primary melanoma to
      sentinel lymph nodes (SLNs) based on a large lymphoscintigraphic database.
      Preoperative lymphoscintigraphy was used to identify and classify SLN drainage
      basins and patterns of drainage. METHODS: Lymphoscintigraphy using intradermally
      administered technetium-99m labeled sulfur colloid was performed on 400
      consecutive patients with malignant melanoma to define lymphatic drainage
      channels and draining SLN basins before surgery. Primary tumor sites consisted of
      head and neck, upper extremity, trunk, and lower extremity. Different types of
      drainage patterns were classified and correlated with different anatomic sites.
      RESULTS: SLN(s) were identified in over 98% of the patients, whereas lymphatic
      drainage channels were successfully identified in 90% of the patients. Drainage
      from the primary site to a single SLN through a single lymphatic channel (type
      IA) was seen in 186 of 400 patients (47%) as the most common type. In patients
      with a single SLN within a single basin (type I-V), the percentage of patients
      with primary lesions in the head and neck, upper extremity, trunk, and lower
      extremity regions were 61%, 79%, 55%, and 78%, respectively. In cases of multiple
      lymphatic channels (type VI-VII), the percentages of patients with primary
      lesions in the head and neck, upper extremity, trunk, and lower extremity regions
      were 24%, 8%, 36%, and 19%, respectively. CONCLUSION: Various drainage patterns
      were noted from primary melanomas in different anatomic sites. Preoperative
      lymphoscintigraphy is important in establishing the SLN basins for harvesting the
      SLN(s).

PMID- 15722818
TI  - Demonstration of excessive metabolic activity of thoracic and abdominal muscles
      on FDG-PET in patients with chronic obstructive pulmonary disease.
AB  - PURPOSE: The purpose of this study was to determine if an FDG-PET study was able
      to visualize muscle uptake of the chest and abdomen in patients with chronic
      obstructive pulmonary disease (COPD). METHODS: This study included 25 patients
      with COPD and 25 patients without COPD who had undergone a FDG-PET study. The
      nonattenuation-corrected images were used to determine the degree of FDG uptake
      in the intercostals, subscapular, abdominal rectus, and abdominal oblique
      muscles. The intensity of uptake in the muscles was rated on a 4-point grading
      scale with 1 being less, 2 the same, 3 slightly more, and 4 markedly more intense
      than the sternum. RESULTS: Thirteen patients with COPD demonstrated FDG activity
      in the intercostal muscles that was equal to or greater than the sternum and the
      tracer was demonstrated predominantly in the inferolateral chest wall (n = 8),
      the entire lateral chest wall (n = 2), the posteroinferior chest wall (n = 2),
      and the entire chest wall (n = 1). In all 13 patients with COPD who demonstrated
      FDG activity in the abdominal oblique muscles, the site of muscle activity was
      predominantly in the anteroinferior abdominal wall (n = 8), the lateral wall (n =
      4), and the anterior wall (n = 1). In patients without known COPD, the frequency
      and intensity of uptake in the muscles were less than those with the disease.
      CONCLUSION: This study demonstrates the ability of FDG-PET imaging to assess
      muscle function in respiratory disorders and may prove to be of some value in
      further characterizing this disorder.

PMID- 15722819
TI  - Honda sign and variants in patients suspected of having a sacral insufficiency
      fracture.
AB  - PURPOSE: The purpose of this study was to reassess whether the Honda sign (HS)
      and its variants on bone scans can be used to differentiate an insufficiency
      fracture (IF) of the sacrum from a metastasis and to evaluate extrapelvic tracer
      accumulation in patients suspected of having a sacral IF. METHODS AND MATERIALS:
      We retrospectively reviewed 34 bone scans of 26 patients suspected of having a
      sacral IF between January 1998 and June 2003. RESULTS: Twenty-four of the
      patients had a sacral IF and 1 had a sacral metastasis from prostate cancer and
      another from lung cancer. The bone scans of only 15 (63%) of the 24 patients with
      a sacral IF exhibited the HS, 8 (33%) scans exhibited variants, and 4 (4%) scans
      showed whole-sacrum uptake. One of the 2 patients with metastasis exhibited the
      HS and the other exhibited a variant. The sensitivity and positive predictive
      value of HS plus its variants as diagnostic criteria for sacral IF were 96% and
      92%, respectively. Seventeen patients (71%) had extrasacral accumulation. The
      most common site was the pubic bone (50%, 12 of 24), and the second most common
      site was the spine (46%, 11 of 24), where the accumulation was the result of a
      compression fracture or degenerative joint disease of the spine. CONCLUSIONS: A
      "Honda sign or variation" with evidence of fractures elsewhere or no evidence of
      other metastatic disease should be strong evidence for a sacral insufficiency
      fracture. The likelihood of having a solitary metastasis to the sacrum is small.

PMID- 15722820
TI  - Diagnostic value of FDG PET and salivary gland scintigraphy for parotid tumors.
AB  - PURPOSE: The purpose of this study was to examine the diagnostic value of the
      combination of F-18 fluorodeoxyglucose (FDG) PET and Tc-99m pertechnetate
      salivary gland scintigraphy in parotid tumors. MATERIALS AND METHODS: Seventy-two
      patients with benign parotid gland tumors (n = 52), malignant parotid tumors (n =
      12), and inflammation (n = 8) underwent both FDG PET and salivary gland
      scintigraphy within 1 week, and 66 of the patients also underwent gallium
      scintigraphy. All patients were negative on their first fine-needle aspiration
      (FNA). RESULTS: Malignant parotid tumors showed significantly higher FDG uptake
      (standard uptake values [SUVs]) than both benign tumors and inflammation, except
      in Warthin's tumor (5.82 +/- 3.95 vs. 2.07 +/- 1.33; P <0.01). Although the SUV
      values of Warthin's tumor and malignant parotid tumors overlapped somewhat,
      Warthin's tumor did demonstrate increased radiotracer uptake, and it was reliably
      distinguished from other parotid gland tumors by the use of salivary gland
      scintigraphy. Considering a SUV value >3 as being positive for malignancy and
      excluding Warthin's tumor on the basis of salivary gland scintigraphy,
      sensitivity and specificity of FDG PET were 75% and 80%, respectively. These
      results were superior to those of gallium scintigraphy (58% and 72%,
      respectively). CONCLUSIONS: Although the diagnostic value of FDG PET in the
      differentiation of malignant from benign parotid gland tumors was limited because
      of the high FDG uptake in some benign tumors, and particularly pleomorphic
      adenomas, combining salivary gland scintigraphy with FDG PET may help to negate
      this drawback, and this combination may be a more promising approach for
      differentiation of various parotid gland tumors in patients compared with
      nondiagnostic needle aspiration.

PMID- 15722822
TI  - Intraluminal FDG uptake in a rectal polyp detected with PET CT: identification of
      an unsuspected synchronous primary bowel tumor.

PMID- 15722821
TI  - PET demonstration of left atrial appendage in chronic atrial fibrillation.

PMID- 15722823
TI  - Reflux esophagitis secondary to chemotherapy detected by serial FDG-PET.

PMID- 15722824
TI  - Rim-like FDG uptake in the gallbladder wall secondary to cholestasis from common
      bile duct obstruction.

PMID- 15722825
TI  - Detection of a solid pseudopapillary tumor of the pancreas with F-18 FDG positron
      emission tomography.

PMID- 15722826
TI  - Accumulation of Tc-99m HDP in adductor magnus caused by squatting exercises.

PMID- 15722827
TI  - Normal F-18 FDG vertebral uptake in Paget's disease on PET scanning.

PMID- 15722828
TI  - Sarcoidosis demonstrated by FDG PET imaging with negative findings on gallium
      scintigraphy.

PMID- 15722829
TI  - Compression of the anterior mediastinum by uremic tumoral calcinosis unusually
      involving the sternoclavicular joint.

PMID- 15722830
TI  - Tl-201 SPECT and F-18 FDG PET for assessment of glioma recurrence versus
      radiation necrosis.

PMID- 15722831
TI  - F-18 FDG PET imaging of metastases from soft tissue myoepithelioma.

PMID- 15722832
TI  - False negative F-18 FDG PET/CT in nonsmall cell lung cancer bone metastases.

PMID- 15722833
TI  - Current readings in nuclear medicine.

PMID- 15722838
TI  - The risks of blood transfusions involve donors as well as patients.

PMID- 15722839
TI  - Prevention of drowning in infants and children.
AB  - Drowning is among the leading causes of death in children under 5 years of age.
      Yet it need not be, as most drowning is often preventable. The author discusses
      this important topic for all nurses and parents.

PMID- 15722840
TI  - Management of increased intracranial pressure: a primer for the non-neuro
      critical care nurse.
AB  - Brain edema and the resulting increase in intracranial pressure may be the result
      of several conditions: head trauma, intracranial hemorrhage, embolic stroke,
      infections, tumors, and alterations in cerebral spinal fluid production or
      absorption. At times, these patients may be treated outside of the neurological
      intensive care unit (ICU) for a variety of reasons. Therefore, general critical
      care nurses may find themselves in the position of caring for these patients.
      Maintaining expertise outside of one's area of focus is increasingly difficult to
      do, and the non-neuro critical care nurse may be unfamiliar with some of the
      newer research findings and trends in treating these patients. The purpose of
      this article is to review several of the concepts of neurological care and to
      update critical care nurses in various newer approaches to caring for patients
      with increased intracranial pressure.

PMID- 15722841
TI  - Enhanced external counterpulsation.
AB  - Ischemic heart disease that is refractory or resistant to medical management is a
      concern to health team members, patients, and their families. These patients are
      limited in their abilities to perform activities of daily living and often find
      it difficult to exercise which negatively affects their quality of life. Some
      patients are confined to bed rest due to these limitations. Enhanced external
      counterpulsation (EECP) is a noninvasive outpatient procedure that has been shown
      to improve the patient's quality of life by decreasing ischemic symptoms and
      permitting increased activity. This article reviews the basic principles of EECP
      therapy and identifies the goals and benefits for the patient. Helpful tips and
      observations are discussed as to the use of this treatment using evidence-based
      research.

PMID- 15722844
TI  - Pivotal role of platelets in critical illness: evidence behind clinical
      interventions.
AB  - Arteriosclerosis, chronic renal failure, and diabetes are all diseases in which
      the platelet cycle plays an important role. Effective interventions for these
      diseases are emerging from vascular biology in general and from the study of
      platelets in particular. Platelet cell processes are powerful modulators of
      immunology, thrombosis, fibrinolysis, and angiogenic responses. Platelet active
      drugs intervene in platelet activation, adhesion, aggregation, and secretion. The
      purpose of this article is to link the unfolding of platelet cell processes and
      the impact of platelet active medication therapy to the care of critically ill
      patients with selected diseases.

PMID- 15722845
TI  - A personal reflection: surviving professional development.
AB  - The embarkation of a postgraduate program differs by the individual. For some,
      it's like a homecoming. For others, it becomes a bizarre and surreal world more
      akin to the likes of Franz Kafka, Tom Robbins, and H. R. Giger than Merriam
      Webster. The author describes the experience of returning to the collegiate world
      in her own inimitable style.

PMID- 15722846
TI  - Use of a specialized transport team for intrahospital transport of critically ill
      patients.
AB  - The transport of critically ill patients is challenging for nurses and patients
      alike. It is imperative that patient safety be the primary focus. The use of a
      specialized transport team can help to alleviate many of the adverse effects of
      the transport.

PMID- 15722847
TI  - Making sense of conflicting research findings.
AB  - The purpose of this article is to help readers interpret research findings. Many
      research studies with conflicting results are published each year. This article
      will help the reader to understand the research process and aid in interpreting
      the findings to determine their appropriateness and/or applicability to oneself
      or one's patients.

PMID- 15722850
TI  - The nursing shortage: why we stay, why we leave, and why we never considered
      nursing as a career in the first place.

PMID- 15722863
TI  - The epidemiology of HIV among Mexican migrants and recent immigrants in
      California and Mexico.
AB  - For Mexican migrants and recent immigrants, the impact of migration from Mexico
      to California has the potential to lead to an increased risk for HIV infection.
      Until recently, the prevalence of HIV in Mexico and among Mexican migrants in
      California appeared to be stable and relatively low. Recent studies have raised
      new concerns, however, that the HIV epidemic may expand more aggressively among
      this population in the coming years. Unfortunately, the insufficient amount of
      data available within recent years makes it difficult to fully assess the
      potential for rapid spread of the HIV epidemic among this population.
      Consequently, there is a critical need for an ongoing binational surveillance
      system to assess prevalence and trends in HIV/STD/TB disease and related risk
      behaviors among this population both in Calfornia and within this population's
      states of origin in Mexico. This enhanced epidemiologic surveillance system
      should provide improved data on the subpopulations at the highest risk for
      HIV/STD/TB, such as men who have sex with men, and should provide the opportunity
      to evaluate the impact of migration on the transmission dynamics, risk behaviors,
      and determinants of behavior on each side of the border. It is essential that
      this potential threat be assessed and that intervention programs are developed
      and implemented to combat this possible escalation in the HIV epidemic.

PMID- 15722864
TI  - Migration and AIDS in Mexico: an overview based on recent evidence.
AB  - OBJECTIVES: Provide an overview of the relation between migration to the United
      States and AIDS cases in Mexico. Characterize the sexual behaviors of Mexican
      migrants. Describe HIV/AIDS prevention and clinical attention actions developed.
      METHODS: The following were analyzed: AIDS cases databases, various prevalence
      studies, the migrants survey, and information of the Ministries of the Interior
      and of Health. A documental analysis was undertaken of works published between
      1992 and 2000 on migration and AIDS. RESULTS: In terms of their sexual practices,
      migrants in the past year had more sexual partners, tended to use a condom in
      their most recent relation in greater proportion, and had greater use of injected
      medicines and drugs. Two bi-national programs undertake epidemiological
      surveillance activities, while several initiatives have used innovative formats
      to provide prevention information to migrants. Imminent universal coverage leaves
      the challenge to assure quality of attention for migrants. CONCLUSIONS: Studies
      to evaluate the impact of international migration on distribution of infected
      persons will be indispensable to establish priorities in prevention and attention
      among migrants. More information is needed on bi-national health projects to
      understand the impact they may have in prevention, while continuity of the
      prevention initiatives must be guaranteed. Attention to migrants in bi-national
      contexts requires information exchange agreements on migrants living with the
      HIV/AIDS.

PMID- 15722865
TI  - HIV prevention with Mexican migrants: review, critique, and recommendations.
AB  - Charged with the task of reviewing the research outcome literature on HIV
      prevention with Mexican migrants in the United States, the following broad
      observations and conclusion were made: (1) there is little research on this
      specialized topic of concern; (2) the research that exists reflects an overly
      individualistic behavioral science approach designed to reduce individual risk
      factors, with little regard for structural and environmental factors that
      influence HIV risk; and (3) there is a compelling need to develop better
      theoretic frameworks for understanding the complex and dynamic social and
      cultural processes influencing sexual behavior among Mexican migrants so as to
      better inform HIV prevention efforts with this unique and diverse Latino(a)
      population.

PMID- 15722866
TI  - HIV health care services for Mexican migrants.
AB  - This article reviews the literature on HIV/AIDS health care services for Mexican
      migrants in the United States. Because so little research has been conducted on
      Mexican migrants per se, we include literature on Latinos/Hispanics in the United
      States, because some characteristics may be shared. Furthermore, we focus special
      attention on data from California because it is on the front line of issues
      regarding health care for Mexican migrants. The types of health care services
      needed to improve on the quality of care provided to Mexican migrants living with
      HIV are highlighted, and recommendations are made for future interventions,
      research, and binational collaborations.

PMID- 15722867
TI  - Policy perspectives on public health for Mexican migrants in California.
AB  - This analysis focuses on public policies that affect primary HIV prevention and
      access to HIV care for Mexican migrants residing in California. Policy or
      structural level interventions, as opposed to behavioral or psychologic
      interventions, help to shape the environment in which people live. We use a
      conceptual model for policy analysis in public health to understand better the
      challenges faced by Mexican migrants. We assess potential policy level
      interventions that may serve as barriers to or facilitators of primary HIV
      prevention and care for Mexican migrants. Among potential barriers, we discuss
      restrictions on public health services based on legal immigration status, limits
      placed on affirmative action in education, and laws limiting travel and
      immigration. Under potential facilitators, we discuss community and migrant
      health centers, language access laws, and the use of community-based groups to
      provide prevention and treatment outreach. We also report on the limited research
      evaluating the implications of these public policies and ways to organize for
      more responsive public policies.

PMID- 15722868
TI  - Management of HIV wasting syndrome: a consensus conference.

PMID- 15722869
TI  - Efficacy of selected treatments of HIV wasting: a systematic review and meta
      analysis.
AB  - PURPOSE: To assess the efficacy of recombinant human growth hormone (rhGH),
      testosterone, and anabolic steroids in the treatment of HIV wasting. METHODS: A
      systematic review and meta-analysis of studies published in English since 1996
      was conducted. Studies of anabolic steroids, testosterone, and rhGH in treatment
      of HIV wasting reporting the efficacy outcomes of body composition measures, work
      output, or health-related quality of life (QoL) were eligible. Meta-analyses were
      performed for mean pre-post change in lean body mass (LBM), the within-study mean
      difference in pre-post change for LBM, and of odds ratios for certain safety
      events. RESULTS: A total of 18 studies met inclusion criteria for this review.
      CONCLUSION: The 3 treatments for HIV wasting assessed--rhGH, testosterone, and
      anabolic steroids--all demonstrated significant efficacy in increasing LBM as
      compared with placebo. Although meta-analysis did not indicate any statistically
      significant differences between these agents in the degree of efficacy in this
      outcome, the Food and Drug Administration-approved dose of rhGH may have
      advantages over the other 2 therapies in terms of improvements in functional
      capacity and QoL.

PMID- 15722870
TI  - Pathogenesis and consequences of HIV-associated wasting.
AB  - Weight loss is a negative prognostic indicator in patients infected with HIV.
      Mortality rates rise measurably with as little as 3-5% weight loss over 6 months.
      The sensitivity of this measure is at least partly due to the correlation between
      weight loss and a metabolic cachexia that has been observed with other
      infections, trauma, and some cancers. However, the cachexia in patients with HIV,
      commonly termed wasting, may also be due to, or exacerbated by, reduced caloric
      intake, gastrointestinal dysfunction, or metabolic abnormalities independent of
      abnormal energy expenditure. In patients with HIV wasting, therapies should be
      directed both at reversing the underlying source of protein energy malnutrition
      and at other factors that may be contributing to weight loss.

PMID- 15722871
TI  - Challenges to diagnosis of HIV-associated wasting.
AB  - There is a wide variability in the clinical presentation of the protein energy
      malnutrition often characterized as wasting in patients infected with HIV.
      Moreover, the clinical presentation has evolved over time. Initially, protein
      energy malnutrition was characterized by profound weight loss and depletion of
      body cell mass (BCM). Recently, unrelated concurrent metabolic abnormalities,
      such as lipodystrophy, may complicate the diagnosis of HIV wasting. Although
      measures of BCM are relatively accurate for the diagnosis of HIV wasting, the
      optimal tools for assessing BCM are not necessarily available to the clinician.
      From the practical standpoint, HIV wasting may be a self-evident diagnosis in
      advanced stages, but effective interpretation of the early signs of HIV wasting
      requires familiarity with other complications included in the differential
      diagnosis.

PMID- 15722872
TI  - Collaborative recommendations: the approach to diagnosis and treatment of HIV
      wasting.
AB  - Loss of lean body mass in patients with HIV, commonly referred to as wasting,
      remains a significant threat to outcome in the era of highly active
      antiretroviral therapy. It does not require advanced immune deficiency to
      progress. It is appropriate to reevaluate guidelines for diagnosis and treatment
      of wasting in the context of the increasing detail with which the risks and
      causes of HIV wasting are being understood. A wide range of therapies can be
      effective in preventing weight loss, but the pharmacologic options for restoring
      body cell mass, a key measure of HIV wasting, are far more limited. A
      collaborative meeting of clinicians and researchers with an interest in HIV
      wasting was held to evaluate published guidelines in the context of current
      clinical data.

PMID- 15722897
TI  - Editorial: symposium on nuclear imaging in dementia and depression.

PMID- 15722898
TI  - Radiotracer development in psychiatry.
AB  - Over the last 20 years a number of radiotracers that target various
      neurotransmitter systems have been developed for use in imaging studies in
      psychiatry, but there are many more targets still to be investigated. The
      development of a radiotracer for clinical positron emission tomography (PET) or
      single photon emission computed tomography (SPECT) neuroimaging studies can be a
      complex and lengthy process with few imaging agents successfully progressing into
      clinical human studies. One of the most challenging aspects in the procedure is
      the development of a rapid and simple radiosynthesis protocol to obtain the
      potential radiotracer with adequate specific activity, isolated radiochemical
      yield and radiochemical purity for human imaging. Once a candidate has been
      radiolabelled, full characterization of the radiotracer is required before it can
      be used in clinical human studies. Pre-clinical studies include investigation
      into the binding distribution, pharmacokinetics, metabolism, toxicology and
      dosimetry of a radiotracer. There are many points during the development
      procedure where a potential radiotracer can be rejected. Due to interspecies
      differences the development of a radiotracer can either go too far with an
      unsuccessful candidate or can potentially lead to rejection of a candidate too
      soon. It is only when the radiotracer has been used in humans can we be certain
      that a radiotracer is a useful imaging agent for clinical research studies. The
      development of new technologies, such as micro-PET or SPECT can only improve our
      ability to predict the success of a radiotracer.

PMID- 15722899
TI  - Emission tomography in dementia.
AB  - Dementia is a chronic brain syndrome with enormous impact on health care
      provision. Emission tomography (single photon emission computed tomography
      (SPECT) and positron emission tomography (PET)) provides a unique tool to
      investigate functional and neurochemical changes, both in those with established
      dementia and in those at risk of subsequent cognitive decline. Alzheimer's
      disease is characterized by bilateral temporoparietal hypoperfusion on SPECT and
      hypometabolism on PET, which may precede the onset of dementia as similar changes
      can be demonstrated in those with mild cognitive impairment and in those
      genetically at risk of developing Alzheimer's disease. In dementia with Lewy
      bodies medial parietal and occipital perfusion deficits are seen together with
      pre-synaptic and post-synaptic dopaminergic changes, most particularly a
      reduction in the striatal pre-synaptic dopamine transporter which can be
      visualized using appropriate ligands (e.g., (123)I-FP-CIT). Vascular dementia is
      associated with multiple, asymmetric, perfusion deficits in multi-infarct
      dementia. In contrast, subcortical vascular dementia is associated with reduced
      perfusion but preserved oxygen extraction fraction on PET. Fronto-temporal
      dementia is characterized by both hypometabolism and hypoperfusion in fronto
      temporal lobes, though hypometabolism appears more extensive, affecting large
      areas of the cerebral hemispheres. Longitudinal studies of treatment response in
      Alzheimer's disease with cholinergic drugs have found changes in regional blood
      flow and nicotinic and muscarinic receptor function in those patients who respond
      to treatment. Currently, emission tomography is widely used for assisting with
      clinical differential diagnosis. Future developments will entail the development
      and application of more specific neurochemical ligands and those which bear a
      closer relationship to the underlying disease processes, including markers of
      tau, amyloid and synuclein pathology.

PMID- 15722900
TI  - The use of single photon emission computed tomography in depressive disorders.
AB  - Single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) have advanced our understanding of the biological underpinnings
      of depression. There is, however, considerable variability in the literature.
      Depression is a complex disorder with marked heterogeneity in diagnosis and
      treatment. There is also evidence of heterogeneity in pathophysiology. In
      addition, the literature is marked by inconsistencies in the use of imaging
      techniques and data-analytical procedures. In this review we have attempted to
      focus on the SPECT studies that have used more refined methodologies and more
      homogenous clinical sub-groups of patients. We have focused on the main
      diagnostic sub-types of depression and on specific issues such as treatment
      response, correlates of neuroimaging abnormalities in depression, and so-called
      'emotional circuitry' - the connectivity of regions implicated in depression. The
      future of molecular imaging in depression will be determined by the pace of the
      development of useful ligands and the exciting opportunities emerging in the
      field of imaging genomics. Future studies must attend to several key confounds
      including clinical heterogeneity, medication and the problems surrounding
      recruitment of drug-naive patients. It remains the case that longitudinal studies
      are the design of choice if questions relating to state and trait are to be
      addressed. Molecular imaging will be used increasingly to quantify neuroreceptor
      and transporter binding, and the activity of neurtransmitters, allowing the
      neurochemistry of this complex condition to be explored.

PMID- 15722901
TI  - UK audit of left ventricular ejection fraction estimation from equilibrium ECG
      gated blood pool images.
AB  - PURPOSE: To examine the variability of results obtained from computer analysis of
      left ventricular gated blood pool (LVGBP) images by nuclear medicine centres in
      the UK. METHODS: Twelve data sets of LVGBP images were distributed via commercial
      software suppliers to nuclear medicine centres in the UK. Two of the data sets
      were duplicates and three were acquired from the same patient with different
      total counts in the images. The quality of the images was also variable and two
      images had poorly defined left ventricular walls. A questionnaire was used to
      identify the parameters used during the analysis and to give an indication of the
      number of LVGBP scans per year routinely carried out by each centre as well as
      report the results obtained from the analysis. RESULTS: Results were received
      from 63 nuclear medicine centres using 77 computer systems. The vast majority of
      participants (57) carried out fewer than 10 scans per month. Only two centres
      performed more than 30 scans per month. Sixteen centres did not quote a minimum
      normal value for left ventricular ejection fraction (LVEF) and 36 did not record
      a maximum value. The remainder recorded between 0.40 and 0.60 for the minimum of
      normal range and 0.60-0.90 for the maximum of normal range. Analysis of returns
      showed that LVEF estimates for the data sets were highly variable between centres
      and computer systems. The overall standard deviation of results compared to the
      mean for each study was 0.076. Approximately half this variation was due to
      systematic variation between centres. The overall precision taking into
      consideration this systematic variation, was 0.055. Lower variability was found
      between studies with higher overall counts and this was highly significant.

PMID- 15722902
TI  - Systematic review of the prognostic effectiveness of SPECT myocardial perfusion
      scintigraphy in patients with suspected or known coronary artery disease and
      following myocardial infarction.
AB  - OBJECTIVES: In patients with suspected or known coronary artery disease (CAD), or
      following myocardial infarction (MI), assessing the degree of ischaemia is
      important from a prognostic and therapeutic point of view. Single photon emission
      computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) is a non
      invasive technique that allows the presence, location and extent of ischaemia to
      be determined. The aim of this systematic review was to assess the prognostic
      effectiveness of SPECT MPS. METHODS: We sought prognostic studies involving
      SPECT, exercise tolerance testing (ETT) and/or coronary angiography (CA) in
      people with suspected or known CAD, or following MI. Outcomes included cardiac
      death, non-fatal MI and revascularization. We searched the following databases:
      MEDLINE, PREMEDLINE, EMBASE, BIOSIS, Science Citation Index, the Cochrane
      Library, the Health Management Information Consortium and the Health Technology
      Assessment Database. RESULTS: Twenty-one observational studies enrolling 53,762
      people reported the general prognostic value of SPECT MPS. In multivariate
      analysis, SPECT MPS variables yielded both independent and incremental value to
      combinations of clinical, ETT and angiographic variables in predicting cardiac
      death or non-fatal MI. Three comparative studies reported lower revascularization
      rates following a SPECT MPS-CA strategy (6-21%) compared with direct CA (16-44%).
      Four observational studies enrolling 2106 people reported the prognostic value of
      SPECT for patients following MI. In multivariate analysis including clinical
      history, ETT, SPECT MPS and angiographic variables, strategies involving SPECT
      MPS provided independent and incremental prognostic performance in predicting
      future cardiac events. CONCLUSIONS: SPECT MPS provides important additional
      information to that from ETT and/or CA that helps to risk-stratify patients with
      suspected or known CAD or following MI, enabling them to be managed more
      appropriately. Increasing the use of strategies involving SPECT MPS may identify
      lower risk patients for whom invasive CA might be avoided.

PMID- 15722903
TI  - Attenuation correction of myocardial SPECT studies using low resolution computed
      tomography images.
AB  - OBJECTIVES: Artefacts caused by tissue attenuation can create problems in the
      interpretation of myocardial perfusion studies. This study aimed to determine if
      attenuation correction using the 'Hawkeye' low-resolution X-ray computed
      tomography facility attached to a GE Millennium VG gamma camera reduced
      attenuation artefacts in our patient group. This technique offers potential
      advantages over isotope transmission methods of attenuation correction because of
      the lack of noise in the transmission images. METHODS: Ninety-four patients (64
      males, 30 females) underwent stress/rest myocardial perfusion imaging using
      (99m)Tc tetrofosmin (188 studies). Semi-quantitative analysis of the attenuation
      corrected and non-corrected perfusion images was carried out using proprietary
      software (Emory ECToolbox). RESULTS: No significant differences between
      attenuation corrected and non-corrected images were seen in the septal, lateral
      or apical segments. Attenuation correction produced a significant reduction in
      the defect scores in the inferior segment indicating the presence of attenuation
      artefacts. This was more marked in male patients. The incidence of attenuation
      artefacts in the inferior segment increased with weight although patients of
      normal weight also showed attenuation artefacts. The changes in the anterior
      segment were more difficult to interpret particularly in females, with
      attenuation correction increasing the defect score in some patients. Minor
      degrees of mal-registration (even of 1 pixel) between emission and transmission
      images increased the likelihood of creating a defect. CONCLUSION: Attenuation
      correction using Hawkeye is likely to improve diagnostic accuracy in men, but is
      less likely to be useful in women.

PMID- 15722904
TI  - FDG PET as a procedure for detecting simultaneous tumours in head and neck cancer
      patients.
AB  - AIM: The presence of simultaneous primary tumours in other regions affects the
      prognosis and management decisions of head and neck cancer patients. Therefore,
      early detection of these tumours is necessary. Recent improvements in positron
      emission tomography (PET) have made it possible to examine the patient's whole
      body. The present study was undertaken to evaluate the clinical contribution of
      whole-body PET using fluorodeoxyglucose (FDG) for head and neck cancer patients.
      METHODS: Fifty-three consecutive patients with previously untreated head and neck
      cancer were examined. Whole-body FDG PET imaging was performed at 1 h after
      injection of (18)F-FDG. A 3-D acquisition was undertaken and iterative
      reconstruction was performed. The final diagnosis of simultaneous primary tumour
      was established by histological findings or clinical follow-up. RESULTS: Of 53
      patients, six (11%) had evidence of simultaneous primary tumour. In five of these
      six patients, simultaneous primary tumours (two gastric cancer; one colon cancer;
      one pancreatic cancer; one thyroid cancer) were found by FDG PET. One more
      patient was found to have prostate cancer on the basis of blood test but this was
      not detected by FDG PET. In none of the remaining 47 patients, were additional
      simultaneous primary tumours found by FDG PET or any of the other routine
      examinations or during follow-up. CONCLUSIONS: The results of this study show a
      high rate of simultaneous primary tumour in patients with primary head and neck
      cancer. FDG PET appears to be a promising imaging modality for the detection of
      simultaneous tumours in head and neck cancer patients.

PMID- 15722906
TI  - Sternal uptake on bone scintigraphy: age-related variants.
AB  - BACKGROUND: When reporting bone scans, it is important to distinguish between
      normal variants and skeletal pathology involving the sternum. There are only
      limited reports dealing with age-related normal variants of the sternum on bone
      scintigraphy. METHODS: We have studied the age-related variants of sternal uptake
      on bone scintigraphy. In a prospective study, 152 consecutive patients (66 males
      and 86 females) undergoing whole-body bone scanning, and who had no symptoms
      associated with the sternum, were evaluated for patterns of normal sternal
      uptake. Three hours after intravenous injection of (99m)Tc-methylene
      diphosphonate ((99m)Tc-MDP), whole-body bone scans in the anterior and posterior
      projections were acquired. Patterns of sternal uptake, including the sites and
      distribution of increased and decreased uptake, were analysed using age-related
      groups. RESULTS: Three patterns of tracer uptake in the sternum were recognized:
      a uniform pattern was most common in children (< or =12 years); a heterogeneous
      uptake pattern was frequently seen in adolescents, young adult and adult groups;
      and a segmented pattern was commonly seen in the geriatric group (>60 years). A
      predominant focal finding was a hot spot at the angle of Louis. In addition,
      there were focal spots of decreased tracer uptake in the lower sternum, just
      above the xiphoid process, and spots of increased tracer uptake in the body of
      the sternum. Such focal spots were not seen in subjects of less than 12 years of
      age. CONCLUSION: Evolutionary changes of the sternum appear to exist throughout
      life. There are age-related normal variants of sternal uptake on bone
      scintigraphy.

PMID- 15722905
TI  - Comparison between Tc-HMPAO labelled white cells and Tc LeukoScan in the
      investigation of inflammatory bowel disease.
AB  - OBJECTIVES: (99m)Tc-HMPAO labelled leukocyte imaging (white cell scan) is used in
      the investigation and assessment of patients with inflammatory bowel disease
      (IBD), while (99m)Tc LeukoScan has been used to demonstrate the presence of
      orthopaedic infections and appendicitis. The single-injection technique used for
      the administration of LeukoScan removes the need for handling blood and the
      complex separation and labelling techniques that are required for white cell
      imaging. This study set out to investigate whether LeukoScan could be used to
      image IBD. METHODS: Twenty-two patients under investigation for suspected IBD
      agreed to undergo LeukoScan imaging within 7 days of their routine planar white
      cell scan. Following injection of 650 MBq (99m)Tc LeukoScan planar images were
      acquired at 1, 2 and 4 h and single photon emission computed tomography (SPECT)
      images at 4 h post-injection. RESULTS: When both sets of images were compared to
      the clinical diagnosis, the sensitivity and specificity were 0.88 and 0.83 for
      white cell imaging and 0.88 and 0.50 for LeukoScan SPECT at 4 h. The figures for
      the specificity and sensitivity of the LeukoScan 2 h and 4 h planar images were
      0.44 and 1.00, and 0.75 and 0.50, respectively. When the LeukoScan and white cell
      images were compared, the 4 h LeukoScan SPECT images showed additional areas of
      uptake in 10 patients. CONCLUSIONS: The study demonstrates that LeukoScan locates
      IBD. However, the sensitivity and specificity preclude its use for the routine
      detection of this disease. Comparisons with white cell scan images show that
      LeukoScan is taken up slowly in IBD and also appears in the normal bowel by 4 h.

PMID- 15722907
TI  - In-vivo PET imaging of inducible D2R reporter transgene expression using [11C]FLB
      457 as reporter probe in living rats.
AB  - BACKGROUND: Increasing interest is being shown in a variety of methods for the in
      vivo monitoring of gene expression. Of these, the reporter assay using positron
      emission tomography (PET) has been studied most extensively. METHODS: We
      evaluated tetracycline-induced gene expression using a PET reporter method
      employing the dopamine type 2 receptor (D2R) gene as a reporter gene and
      [(11)C]FLB 457 as a reporter probe. We constructed a plasmid containing the D2R
      gene, whose expression was under the control of the tetracycline-responsive
      element, and transfected it into HeLa-Tet-On cells. D2R messenger RNA (mRNA)
      expression was measured by reverse transcription-polymerase chain reaction (RT
      PCR) and D2R binding in the cultured cells was measured by a binding assay using
      methoxy-[(3)H]raclopride as a ligand. The tetracycline analogue, doxycycline, was
      used to regulate D2R expression. RESULTS: Doxycycline dose- and exposure time
      dependent D2R transgene expression was observed in the mRNA measurements and
      receptor binding in the cells. The stably transfected cells were inoculated into
      nude rats and D2R expression in xenograft tumours was monitored by in-vivo
      receptor binding using PET. Doxycycline-dependent D2R expression was also
      observed in this in-vivo system. The correlation between the magnitude of the
      [(11)C]FLB 457 PET signal and the D2R-expressing cell fraction in the tumours
      showed the usefulness of the D2R-FLB 457 reporter gene-reporter probe system with
      PET for the quantitative evaluation of inducible in-vivo gene expression.
      CONCLUSION: The D2R-FLB 457 reporter gene-reporter probe system should be
      considered as a useful technique for measuring inducible in-vivo gene expression.

PMID- 15722908
TI  - Is MIBI the best choice for the evaluation of hand perfusion during cold test
      provocation?

PMID- 15722912
TI  - [Declaration of the principles for the administration of botulinum toxin].

PMID- 15722950
TI  - Gene expression profile analysis of lymphocytes from Alzheimer's patients.
AB  - Since the function and metabolism of peripheral lymphocytes is known to be
      altered in Alzheimer's disease (AD), a pilot study was carried out to examine
      differences in gene expression profiles of these cells in 16 AD patients and aged
      control probands. Using a cDNA microarray representing 3200 distinct human genes,
      we identified 20 candidate genes whose expression is altered in AD lymphocytes
      compared with the control probands. Among these were the alpha2C-adrenoreceptor
      gene, known to regulate blood pressure and learning, the defensin,
      histocompability complex enhancer-binding protein, carboxypeptidase M, and the Fc
      fragment of IgE known to be involved in cellular and humoral immune responses.
      Others, like human cell death protein, TRAIL, and galectin-4 participate in the
      regulation of apoptosis. Real-time quantitative reverse transcription-polymerase
      chain reaction analysis was performed in order to confirm the expression changes
      in AD lymphocytes, and it could detect down-regulation of defensin and alpha2c
      adrenoceptor genes, while other genes seemed unaltered in their expression,
      including heat-shock protein (hsp90), cholesteryl ester transfer protein, and
      apolipoprotein B100 (apoB). The altered expression profile of these genes might
      be connected with the previously reported AD-specific lymphocyte abnormalities.
      It remains to be elucidated, however, how these genes are related to the
      pathomechanism of dementia and whether the gene expression differences of AD
      lymphocytes reflect disease traits or stage processes.

PMID- 15722951
TI  - Serotonin transporter and tryptophan hydroxylase gene polymorphisms in Chinese
      patients with generalized anxiety disorder.
AB  - BACKGROUND: The serotonin transporter (5-HTT) and tryptophan hydroxylase (TPH)
      gene are important candidate genes for the psychiatric disorders. Many studies of
      patients with anxiety disorders have found abnormalities of serotonin metabolism
      and dysfunction of regulation in the transporter itself. In this study, we
      hypothesize that genetic variation in the 5-HTT and TPH gene may have an effect
      on the etiology of generalized anxiety disorder (GAD). METHODS: Using a
      polymerase chain reaction-based technique, the allele and genotype frequencies of
      three polymorphisms in the serotonin transporter gene (a deletion/insertion
      polymorphism in the transcriptional control region and a variable number of
      tandem repeats in intron 2) and TPH gene (A218C in intron 7) were analyzed in 138
      patients with GAD and 90 healthy controls. These two groups were matched for
      ethnic and geographic origin. RESULTS: The frequencies of 5-HTT gene-linked
      functional polymorphic region (5-HTTLPR) SS (short/short) genotype were
      significantly higher in GAD patients than in control subjects (68% versus 49%,
      chi = 12.274, df = 2, P = 0.002), and the frequencies of S (short) allele
      observed in the GAD patients were higher than those in healthy subjects (79
      versus 71%, chi = 4.063, df = 1, P = 0.044). The odds ratio for the SS genotype
      versus the other two genotypes was 2.33 (95% confidence interval, 1.29-3.86).
      Similarly, the odds ratio for the S allele versus L allele was 1.56 (95%
      confidence interval, 1.01-2.41). The genotypic and allelic distribution of 5-HTT
      VNTR and TPH A218C polymorphisms did not show statistically significant
      differences between patients and controls. CONCLUSION: Our findings support that
      the presence of 5-HTTLPR-SS genotype may increase the risk of GAD.

PMID- 15722952
TI  - Tyrosine hydroxylase Val-81-Met polymorphism associated with early-onset
      alcoholism.
AB  - The present study examined the association of the Tyrosine hydroxylase Val-81-Met
      polymorphism with alcohol dependence. One hundred and fifty-nine patients in a
      psychiatric unit with alcohol dependence were genotyped as well as 92 healthy
      volunteers. The Val allele was more frequent in patients with alcohol dependence
      (69.5%) than in controls (62.5%). This effect was largely due to the association
      with early-onset alcoholism (77.8%), whereas no difference was noted between late
      onset patients and controls. Our results suggest a role for tyrosine hydroxylase
      in early-onset alcoholism.

PMID- 15722953
TI  - Association study of 90 candidate gene polymorphisms in panic disorder.
AB  - OBJECTIVE: In the present investigation we screened a large number of single
      nucleotide polymorphisms in the genes relevant to the neurobiology of anxiety for
      their association with panic disorder (PD). METHODS: The study sample included
      127 patients with PD and 146 healthy control subjects. Using Arrayed Primer
      Extension technology we genotyped 90 polymorphisms in 21 candidate genes of
      serotonin, cholecystokinin, dopamine and opioid neurotransmitter systems. The
      association and haplotype analyses were performed in the whole group (PD-all) and
      in the subgroups of PD comorbid with major depression (PD-comorbid, n = 60) and
      without any comorbidity (PD-pure, n = 42). RESULTS: From the set of 90
      polymorphisms, eight single nucleotide polymorphism markers in eight genes
      displayed at least a nominal association with any of the studied PD phenotype
      subgroups. Several polymorphisms of cholecystokinin, serotonin and dopamine
      systems were associated with PD-all and/or PD-comorbid phenotypes, while pure PD
      was associated only with HTR2A receptor 102T-C (P = 0.01) and DRD1 receptor -94G
      A (P = 0.02) polymorphisms. Haplotype analysis supported an association of the
      cholecystokinin gene TG haplotype with the PD-all group (P = 0.04), whereas DRD1
      receptor CAA and HTR2A receptor AT haplotypes were associated with a lower risk
      for PD-pure phenotype (P = 0.03 and P = 0.04, respectively). CONCLUSIONS: The
      study results suggest that genetic variants of several candidate genes of
      neurotransmitter systems, each of a minor individual effect, may contribute to
      the susceptibility to PD. Our data also indicate that genetic variability may
      have a distinctive influence on pure and comorbid phenotypes of PD.

PMID- 15722954
TI  - A sex-adjusted and age-adjusted genome screen for nested alcohol dependence
      diagnoses.
AB  - Alcohol dependence is a complex disorder with a substantial genetic contribution
      to susceptibility. The Collaborative Study on the Genetics of Alcoholism is a
      multi-site study whose purpose is to detect, localize, and characterize genes
      contributing to this susceptibility. Previous linkage analyses of the trait of
      alcohol dependence in Collaborative Study on the Genetics of Alcoholism have used
      affected sib-pair methods with a dichotomous phenotype definition. In contrast,
      the analysis in this paper uses a sex-adjusted and age-adjusted multiple
      threshold liability model. The use of such a model, in that it includes
      unaffected as well as as affected subjects and in that it utilizes the
      differential severity of a diagnosis scale, should heuristically be more powerful
      than a straight affected sib-pair analysis. Three regions of interest are found
      on chromosome 1 (lod 5.17), chromosome 4 (lod 3.46), and chromosome 8 (lod 4.31).
      The region on chromosome 1 near the marker D1S532 is in the region previously
      reported as linked to alcohol dependence and correlated phenotypes in this
      dataset. The region on chromosome 4 near the alcohol dehydrogenase gene cluster
      has been reported to be linked to alcohol dependence in other studies, as well as
      to the alcohol consumption phenotype 'Maximum Number of Drinks in a 24-Hour
      Period' in this dataset. The region on chromosome 8 near the marker D8S1988 is
      homologous to a section of rat chromosome 5 to which an alcohol consumption
      phenotype has been linked.

PMID- 15722955
TI  - Telomeric length varies with age and polymorphisms of the MAOA gene promoter in
      peripheral blood cells obtained from a community in Taiwan.
AB  - OBJECTIVE: Telomere shortening and increased MAOA gene activity both occur with
      aging. We undertook to develop a predictive model of telomere shortening and to
      investigate the possible association between MAOA gene promoter polymorphisms and
      telomere length as influenced by age and gender. METHODS: A stratified random
      household sample was selected from a community in southern Taiwan. Of 1231
      subjects attending our health-screening program, 441 agreed to have additional
      venous blood withdrawn for DNA extraction and genetic study. Exactly 433 subjects
      completed the questionnaires and genetic analysis. Their telomere lengths were
      distributed (6.4-11.63 kb). RESULTS: The rate of shortening per year was 69 base
      pairs, and the gender difference in length was not statistically significant (F =
      0.091, P = 0.763). The lognormal distribution of telomere lengths was linear. The
      polynomial regression analysis showed Ln (telomere length) = -2.57-0.007 x age -
      0.34 MAOA (adjusted R-square = 0.60). The gender effect on telomere length was
      not statistically significant (P = 0.52). No interaction effects were found
      between age, gender and MAOA gene polymorphisms. The high-activity allele of the
      MAOA promoter polymorphisms were negatively associated with telomere length (P =
      0.013). Structural equation modeling confirmed the null model structure. The
      present data suggest that high-activity MAOA promoter gene polymorphisms, as in
      aging, are a risk factor for telomeric shortening. CONCLUSIONS: Central nervous
      system serotonergic activity correlates with human aggressive behavior and
      depression in many studies, and the MAOA promoter gene may also serve as a
      clinical marker in the treatment of cardiovascular disease. The predictive model
      and table of telomere length presented in this study will provide a quick
      reference for future studies.

PMID- 15722956
TI  - Candidate psychiatric illness genes identified in patients with pericentric
      inversions of chromosome 18.
AB  - Both the long and short arms of chromosome 18 have been consistently identified
      as potential locations for schizophrenia and bipolar affective disorder
      susceptibility genes. We previously described the identification of two
      independent pericentric inversions of chromosome 18 [inv(18)(p11.31;q21.2) and
      inv(18)(p11.31;q21.1)] occurring in two small families in which carriers have
      been diagnosed with schizophrenia and bipolar affective disorder, respectively.
      Using fluorescence in situ hybridization on patient metaphase chromosomes we have
      identified the locations of all four chromosome breakpoints in the inversion
      carriers. Neither pericentric inversion results in a direct gene disruption.
      However, each inversion breakpoint has the potential to perturb local gene
      expression by position effect or by the separation of important regulatory
      (enhancer) sequences from the core gene sequences. Five genes in the localities
      of the breakpoints have been identified as good candidates for the genetic basis
      of psychiatric illness in these families; TTMA, a novel membrane spanning
      protein; TCF4, a basic helix-loop-helix transcription factor; DLGAP1, an
      interactor of the PSD-95 synaptic protein; and ARKL1 and ARKL2, novel members of
      the ubiquitin ligase gene family.

PMID- 15722957
TI  - Examination of the clock gene Cryptochrome 1 in bipolar disorder: mutational
      analysis and absence of evidence for linkage or association.
AB  - Bipolar disorder is associated with malfunctions of the circadian system, which
      regulates individual circadian rhythms and which enables the adaptation to a
      daily 24-h cycle and seasonal change. One of the human circadian clock genes,
      cryptochrome 1 (Cry1) (located on 12q23-q24.1) was analyzed because of its close
      correspondence to a linkage hotspot for bipolar disorder. We found no evidence
      for linkage of 52 bipolar families to two Cry1 flanking microsatellites under
      several parametric and non-parametric models. In order to employ association for
      a more sensitive test, 25 affected subjects selected from families with positive
      LOD scores were screened for mutations by sequencing 9.5% of the Cry1 gene. A
      total of 16 single nucleotide polymorphisms (SNPs) and a 3 base pair insertion
      were identified. However, no mutations with probable functional impact were
      found. These novel SNPs and data on allele frequency and linkage disequilibrium
      structure will be useful for future association analyses. Nine SNPs have been
      analyzed in a set of 159 parent proband triads. Linkage disequilibrium analyses
      using single SNPs and haplotypes showed no association to bipolar
      disease.Additional, more powerful, studies involving Cry1 and other circadian
      clock genes need to be tested before an association of circadian abnormalities
      with bipolar disorder can be excluded.

PMID- 15722958
TI  - Meta-analysis of family-based association studies between the dopamine
      transporter gene and attention deficit hyperactivity disorder.
AB  - INTRODUCTION: Molecular genetic research has mainly focused on the D4 dopamine
      receptor (DRD4) and the dopamine transporter (DAT) genes in attention-deficit
      hyperactivity disorder (ADHD). A recent meta-analysis showed that the DRD4 gene
      has a significant role in the vulnerability to ADHD. OBJECTIVES: With an equal
      number of positive and negative association studies between the 10-repeat of the
      DAT gene and ADHD, a meta-analysis is required for this other candidate gene.
      METHODS: We re-analysed the 13 published family-based association studies between
      ADHD and the DAT gene. Following recent recommendations, different biases were
      specifically assessed, such as the sample-size effect and the time effect.
      RESULTS: The meta-analysis showed no significant association between ADHD and the
      DAT gene (P = 0.21), but an important between-samples heterogeneity (P = 0.0009).
      Odds ratios above 1 are mostly observed in studies with a small number of
      informative transmissions, and decrease with larger sample size. CONCLUSIONS:
      Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT
      gene has at most a minor role in the genetic susceptibility of ADHD. The
      different biases detected herein probably explain the initial impression of a
      significant impact of the DAT gene on hyperactivity.

PMID- 15722959
TI  - Startle modulation in Caucasian-Americans and Asian-Americans: a prelude to
      genetic/endophenotypic studies across the 'Pacific Rim'.
AB  - OBJECTIVES: Deficient prepulse inhibition (PPI) of startle in schizophrenia
      patients and unaffected family members may be a useful endophenotype in studies
      seeking to identify vulnerability genes for schizophrenia. Before expanding such
      studies to include Pacific Rim populations with distinct genetic origins compared
      with North American Caucasian populations, we examined PPI and related startle
      measures in normal North American Caucasian and Asian men. METHODS: One hundred
      and seventy-four consecutive carefully screened right-handed male 18-35 year olds
      completed tests of startle and PPI using bilateral electromyography measures of
      orbicularis oculi. Subjects identified their racial background. RESULTS: Startle
      in Caucasian subjects was of significantly larger magnitude and shorter latency
      compared with Asian subjects; the percent PPI was significantly greater in Asian
      versus Caucasian subjects at 60 and 120 ms prepulse intervals. Group differences
      in PPI but not reflex latency were eliminated when groups were matched for
      startle magnitude on pulse alone trials. Caucasian-American and Asian-American
      groups did not differ significantly in resting blink rate, resting
      electromyography activity, or startle reflex habituation. CONCLUSIONS: Robust
      phenotypic differences in acoustic startle magnitude and latency between
      Caucasian-American and Asian-American populations must be considered in studies
      using startle and PPI as endophenotypes across these populations.

PMID- 15722960
TI  - Serotonin 2A receptor gene polymorphism and personality traits: no evidence for
      significant association.
AB  - A number of studies have observed associations between the serotonin 2A (5-HT2A)
      receptor and mental disorders. Here, we investigated correlations between
      polymorphisms (-1438G/A and 102T/C) of the 5-HT2A gene and personality traits in
      healthy Japanese volunteers (n = 239). The personality traits were evaluated
      using the Revised NEO Personality Inventory (NEO PI-R). The -1438G/A and 102T/C
      were in complete linkage disequilibrium. There was a tendency for associations
      between the genotype and the scores for Agreeableness, Conscientiousness and
      Neuroticism of the NEO PI-R (P = 0.028, 0.039 and 0.062, respectively; analysis
      of variance, uncorrected for multiple testing). Subjects with the A/A of -1438G/A
      (or T/T of 102T/C) appeared to be lower in Neuroticism and higher in
      Conscientiousness than the rest of the subjects. However, the results were
      statistically non-significant after Bonferroni's correction for multiple testing
      of the five scales of the NEO PI-R. Thus, the present study provided no evidence
      for statistically significant associations between the 5-HT2A polymorphisms and
      the personality traits.

PMID- 15722961
TI  - Genomic scan for alcohol craving in Mission Indians.
AB  - Alcohol dependence is a leading cause of morbidity and mortality in Native
      Americans, yet etiologic factors contributing to the disorder remain obscure.
      Complex psychiatric disorders may be influenced by a number of genes that may be
      difficult to detect because each has a small effect on a disorder that is broadly
      defined within a social context. However, such genes might be detected if they
      have a major effect on a more narrowly defined phenotype. Underlying alcohol
      dependence are appetitive drive states or instincts that lead to drug 'craving',
      contribute to compulsive drug usage, and influence relapse following abstinence.
      A whole genome scan in Mission Indian families provides evidence for genetic
      linkage to 'craving for alcohol' on chromosome 5. Identification of genes
      contributing to alcohol craving may give clues to the etiology of the disorder
      and also provide targets for the development of new medications to treat alcohol
      dependence.

PMID- 15722963
TI  - The most important conversation you will have.

PMID- 15722965
TI  - Palliative care: a challenge for orthopaedic nursing care.
AB  - Patients who face chronic, incurable, or life-ending musculoskeletal conditions
      often receive inadequate care either due to a lack of caregiver awareness or
      inattention to maintaining the highest quality at the end of life. Palliative
      care focuses on the comprehensive physical, psychological, social, spiritual, and
      existential needs of patients with life-threatening or debilitating illness.
      Orthopaedic nurses and all nurses in general are challenged to incorporate
      palliative care principles into care planned with patients and families facing
      end-of-life issues. This article addresses the leadership role the National
      Association of Orthopaedic Nurses (NAON) has taken to develop a consensus
      document which endorses the Last Acts Precepts of Palliative Care and affirms the
      need for palliative care with patients who experience life-threatening illness. A
      case study is used to illustrate the opportunity a multidisciplinary team has to
      center care on the individual, while remaining sensitive to the holistic needs of
      the patient for self-determination at the end of life.

PMID- 15722966
TI  - Palliative care--improving the quality of care for patients with chronic,
      incurable musculoskeletal conditions consensus document.

PMID- 15722968
TI  - Outcomes measurement for patients with low back pain.
AB  - Outcomes tracking provides a systematic method of monitoring treatment
      effectiveness and efficiency. A familiarity with outcome measures for the patient
      with low back pain is very important for clinicians working in orthopaedic
      settings, where patients with lumbar pain are prevalent. The clinician must be
      able to evaluate and choose appropriate measurement tools, and understand the
      clinical meaning of measurements to successfully employ these instruments. The
      purposes of this article are to review measurement instruments and to offer
      practical guidelines for selection and use of outcome measures for this
      population. The reliability, validity, sensitivity to change, and utility of
      common outcome measures are discussed. An overview of generic, disease-specific,
      and patient-specific tools is provided, with specific commentary on the use of
      the SF-36, SF-12, Oswestry, Roland Morris, and patient-specific tools. Practical
      guidelines for utilizing outcome measures in clinical practice and the overall
      benefits of outcomes tracking are highlighted.

PMID- 15722970
TI  - Changing paradigm for the treatment of clubfeet.
AB  - Clubfoot is one of the most common pediatric orthopaedic conditions. Until
      recently, surgical management was the treatment of choice. Nonoperative treatment
      techniques, including the Ponseti casting and French physical therapy methods,
      have peeked interest of orthopaedists eager to find a less aggressive treatment
      method that can assure a lasting, good result. Both methods have proven
      successful in reducing the number of patients requiring extensive surgical
      release and, as a result, have become an integral part of pediatric orthopaedic
      practice. A clear understanding of both treatment methods is important for the
      orthopaedic nurse to allow quality nursing care and help assure a successful
      outcome for young patients.

PMID- 15722972
TI  - Usefulness of the SCORE index as a predictor of osteoporosis in women with
      disabilities.
AB  - BACKGROUND: Osteoporosis is widely recognized as a common health problem among
      older women. It has also recently been identified as common in both pre- and
      postmenopausal women with disabilities. Although several clinical indices have
      been developed to identify nondisabled women likely to have low bone mineral
      density (BMD) when tested, studies that have tested the usefulness of these
      clinical indices have excluded women with disabilities. Thus, the usefulness of
      these indices in predicting low BMD and osteoporosis in women with disabilities
      is unknown. PURPOSE: This study examined the ability of one of these indices, the
      Simple Calculated Osteoporosis Risk Estimation (SCORE), to identify women with
      disabilities likely to have low BMD on screening. SAMPLE/DATA COLLECTION: Women
      with disabilities (N = 307) responded to the six-item SCORE index and underwent
      peripheral BMD screening. The sensitivity, specificity, and accuracy of the SCORE
      index in predicting BMD with the criterion of a T-score of </=2.5 were 65.7,
      61.1, and 62.2%, respectively. When a T-score of </=2.0 was used as the
      criterion, the sensitivity, specificity, and accuracy of the SCORE index were
      62.6, 63, and 62.9%, respectively. FINDINGS: The low sensitivity, specificity,
      and accuracy of the SCORE index indicate that it is not a useful predictor of low
      BMD in women with disabilities, incorrectly categorizing almost 40% of the
      sample. A clinical index that includes osteoporosis risk factors present in women
      with disabilities is needed to increase the likelihood that women with
      disabilities will be referred for testing and receive treatment of osteoporosis
      when indicated.

PMID- 15722973
TI  - Fighting infection: an ongoing challenge, part 1.
AB  - Since the beginning of time, infections have been a major cause of disability and
      death of humans in every part of the world. For centuries, little was known about
      what caused infection, how to prevent infection, or how to cure infection. With
      the discovery of sulfa and penicillin in the 1930s, the ability to fight
      infection became reality. During the next six decades, antimicrobials were
      developed to fight bacterial, fungal, and viral infections. It truly seemed as if
      the battle against infection was won, until the rapid and global spread of drug
      resistance began to threaten the effectiveness of all currently available
      antimicrobials. A new phase of the war against infection began, and the search
      for methods of reducing the spread of drug resistance began. Today, it is
      apparent that identifying the agents of infection, understanding how
      antimicrobials are targeted against specific infectious organisms, and practicing
      the judicious application of antimicrobials will help reduce the threat of
      continued escalation of antimicrobial resistance. Part 1 of this three-part
      series will provide an overview of how antimicrobials are designed to target
      specific agents of infection and how drug resistance develops. Parts 2 and 3 will
      examine individual antibacterial, antifungal, and antiviral agents and the
      recommendations for their appropriate use.

PMID- 15722975
TI  - The ABCs of BMPs.
AB  - Bone morphogenetic proteins (BMP) are being increasingly used in orthopaedic
      surgery. These small molecules are capable of inducing bone formation when
      delivered in the appropriate concentration and on the appropriate scaffold. Not
      all BMPs are equally effective, and there are currently only two Food and Drug
      Administration (FDA)-approved "on-label" applications. There are potential
      complications related to off-label use of BMPs that need to be understood. When
      used properly, these molecules have the potential to eliminate the need for iliac
      crest bone graft harvest and improve the speed and success of bone healing.

PMID- 15722978
TI  - Pediatric distal double bone forearm fracture remodeling.
AB  - Children's bones differ from those of adults in their capacity for ongoing growth
      and their ability to adapt to a changing body habitus. Similarly, pediatric
      fractures generally heal more rapidly and have the ability to reshape
      deformities, a process known as remodeling. The following case exemplifies the
      remodeling process of a distal radius fracture over time.

PMID- 15722981
TI  - Autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is characterised histologically by interface
      hepatitis, and serologically by the presence of non-organ and liver specific
      autoantibodies and increased levels of immunoglobulin G. Its onset is often ill
      defined, frequently mimicing acute hepatitis. AIH usually responds to
      immunosuppressive treatment, which should be instituted as soon as diagnosis is
      made. Two types of AIH are recognized according to seropositivity for smooth
      muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney
      microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in
      both. LKM1 positive patients tend to present more acutely, at a younger age and
      commonly have immunoglobulin A deficiency, while duration of symptoms before
      diagnosis, clinical signs, family history of autoimmunity, presence of associated
      autoimmune disorders, response to treatment and long-term prognosis are similar
      in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA
      DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely
      to derive from an immune reaction to liver cell antigens, possibly triggered by a
      mechanism of molecular mimicry, where immune responses to external pathogens,
      e.g. viruses, become directed towards structurally similar self-components. In
      AIH this process would be perpetuated by impairment in immune regulation.

PMID- 15722982
TI  - [The diagnosis of helicobacter pylori infection: guidelines from the Maastricht 2
      2000 Consensus Report].
AB  - The European Helicobacter pylori Study Group (EHPSG), during the Maastricht 2
      2000 Workshop, revised and updated the original guidelines on the management of
      Helicobacter pylori (H. pylori) infection. The present review focuses on the
      diagnostic approach for patients referred to the primary care as well as to the
      specialist. Currently, two diagnostic methods can be used to detect H. pylori:
      invasive (urease test, histological detection, culture, polymerase chain
      reaction, smear examination, string test) or non-invasive (serology, urea breath
      test, antigen stool assay, ''doctor's tests'') tests. These methods vary in their
      sensitivity and specificity, and the choice depends on the situation, for
      example, whether the aim is to detect infection or the success of eradication
      treatment. Urea breath test (UBT) and antigen stool assay are recommended from
      EHPSG in patients without alarm symptoms or under 45 years of age, at low risk of
      malignancy in the ''test and treat strategy''. Confirmation of H. pylori
      eradication following treatment should be tested by UBT; a stool antigen assay is
      the alternative if the former is not available. Important added value can be
      gained from other tests: histology allows evaluation of the status of the mucosa
      while culture allows strain typing and tests for antibiotic susceptibility.

PMID- 15722983
TI  - [Nutritional habits and colon-rectal tumours].
AB  - Following a review of the literature, the relationship between diet and the onset
      of colorectal cancer is analysed starting from the consideration that in Italy
      about 20,000 people every year from carcinoma of the colon and 50% of these do
      not survive. The authors proceed to analyse the epidemiological data which point
      to diet as an aetiological factor in the cancerogenesis of a variety of tumours
      in spite of the fact that none of the individual nutritional components has been
      specifically identified as a triggering and/or protective agent, with the
      exception perhaps of alcohol in the cancer-cirrhosis sequence. They conclude by
      stating that, while continuing to give the correct importance to integrated
      surgical, chemo and radio treatment, to prevent the onset of tumours of the large
      intestine it is useful to associate the support of a complete nutritional
      education, which should be begun as soon as possible, with the canonical
      screening techniques. This educational programme should stress the importance of
      diet as a contributor of protective principles such as fruit, vegetables,
      vitamins and non-absorbable fibres which reduce contact time between the
      carcinogenic substances derived from a prevalently meat diet (cholesterol
      stimulates the production of biliary salts by increasing the quota of
      taurodesoxycolic and lithocolic acid and other carcinogenic factors represented
      by conservants and chemical additives such as nitrates and nitrites which can
      have a carcinogenetic activity) and the intestinal mucosa.

PMID- 15722984
TI  - What do heartburn sufferers expect from proton pump inhibitors when prescribed
      for the first time?
AB  - AIM: Based on several consensus reports, the official goals of gastroesophageal
      reflux disease (GERD) treatment are symptom relief, healing of esophagitis,
      prevention of complications and also prevention of relapses. The aim of the
      present study was to evaluate the expectations of heartburn sufferers referred to
      primary endoscopic examination in a prescribed proton-pump-inhibitor (PPI)
      therapy, also in relation to the official treatment goals. METHODS: A group of 91
      patients has been sent to the Division of Gastroenterology of the Public Hospital
      of Zell am See for a first endoscopic examination because of recurrent GERD
      related symptoms. All patients (59 men, 32 females), mean age 44.8 years (range
      28 to 63 years), treated their symptoms themselves using over-the-counter
      medication and/or life-style modification and diet. Subsequent to endoscopic
      examination and medical prescription all patients were asked about their
      expectations in a prescribed PPI therapy (open technique). RESULTS: Of the
      complete sample, only 4 patients (4.4%) had no real expectations in the
      prescribed antireflux medication. The leading expectations were: 1) an
      improvement in (61%) or elimination of (33%) perceived symptoms; 2) healing of
      esophagitis (50%); 3) in 46% of the patients a return to normal daily life and in
      44% an improvement in quality of life respectively. Thirty-six percent expected
      no further therapy following this initial treatment and 34% no side-effects of
      PPI treatment. CONCLUSIONS: The leading patient-related expectations in PPI
      therapy are related to their perceived symptomatology, an improvement in quality
      of life, healing of esophagitis, and also a long-term efficacy of treatment. Most
      of these factors expected by the patients are in relation to the official
      treatment goals, but especially aspects such as quality of life and normal daily
      activities should be included as endpoints of treatment.

PMID- 15722985
TI  - Acute recurrent diverticulitis is prevented by oral administration of a
      polybacterial lysate suspension.
AB  - AIM: The main cause of acute diverticulitis is the abnormal accumulation of fecal
      bacteria within the diverticular lumen, leading to a balancing between normal
      probiotic microflora and pathogenic species; Gram negative Entero-bacteriaceae,
      mainly Escherichia coli and Proteus spp, are the genders that usually cause the
      disease-related symptoms, due to their ability to adhere to intestinal mucosa.
      The intestine is well known as the largest human lymphoepithelial organ and daily
      produces more antibodies, mainly secretory IgAs, than do all other lymphoid
      tissues. IgAs have different immune and anti-inflammatory properties. The aim of
      this study was to verify the efficacy of an oral immunostimulant highly-purified,
      polymicrobial lysate in the prevention of recurrent attacks of diverticulitis and
      in the improvement of symptoms. METHODS: The study was carried out on 83
      consecutive patients suffering from recurrent symptomatic acute diverticulitis
      and with at least 2 attacks in the previous year; patients were randomly assigned
      to receive (group A) an oral polybacterial lysate suspension or to a no-treatment
      clinical follow-up as controls (group B). RESULTS: A total of 76 patients (41 in
      group A and 35 in group B) terminated the study period. the sums of the scores
      for symptoms, reported on day schedules, were calculated and examined by means of
      ANOVA statistical analysis. Statistical differences between group A vs group B
      were recorded after 1 month (p<0.05) and 3 months (p<0.01) of treatment with the
      oral polybacterial lysate suspension. CONCLUSIONS: Our data suggest that the
      administration of an oral enterovaccine for the prophylaxis of recurrent
      diverticulitis is effective and well tolerated, probably due to a direct
      stimulation of IgA-mediated mucosal defences.

PMID- 15722986
TI  - Intestinal permeability assessment before and after ileal pouch-anal anastomosis.
AB  - AIM: Intestinal permeability is considered an index of anatomic and functional
      integrity of the small intestine mucosa. Altered intestinal permeability has been
      suggested to be a possible cause of pouchitis. Aim of this paper was to assess
      variations in intestinal permeability during the first year of a pouch
      reconstruction. METHODS: Intestinal permeability (IP) was investigated in 8
      ulcerative colitis patients before and after total proctocolectomy, with ileal
      pouch-anal anastomosis (IPAA), by means of the cellobiose/mannitol test. To each
      patient a basal test (before surgery) and 3 more tests during a 1 year follow-up
      were administered. RESULTS: Individual data were altered despite clinical
      findings in 9 of 30 IP measured values. An overall pattern of unaffected
      permeability was however shown and none of our patients, during the first year
      follow-up, has developed pouchitis. CONCLUSIONS: Six of the 8 investigated
      patients presented at least 1 altered IP value. A longer follow-up aimed to
      further investigate patients beyond the first year after IPAA confection as to
      the occurrence of pouchitis and its possible correlation with a previous
      permeability alteration of the pouch mucosa is in progress.

PMID- 15722987
TI  - Epidemiological features of virus hepatitis in the Russian Army.
AB  - The last decade of the 20th century was characterized by the improvement of the
      virus hepatitis (VH) in diagnosis system, on the one hand, and by the change in
      the VH etiologic structure, on the other hand. This was due to the influence of
      several processes: the ongoing decrease of hepatitis A (HA) morbidity rate in
      most regions, the increase of hepatitis B (HB) morbidity, the introduction of
      methods for hepatitis C (HC) diagnosing and reporting, the emergence and
      progressive increase of VH number with combined etiology, the improvement of
      diagnosing and reporting of chronic VH. Analogous processes occurred similarly in
      the Armed Forces (AF) of Russia. Thus, VH in the army has definite epidemiologic
      features. It must be taken into account not only by military healthworkers but by
      civil specialists as well. This can be of critical importance when operating
      under extreme conditions.

PMID- 15722988
TI  - Obesity and nutritional behavior within a historical perspective.
AB  - Obesity is an ever increasing pathological condition in Western countries.
      Genetic, metabolic, social and cultural factors play different roles in the
      varying pictures of obesity, together with nutritional behavior. This research
      proposes to formulate a comparison through the literary sources of the classical
      world, so as to determine the modalities with which obesity and nutritional
      habits have been perceived in the past. In Greek and Roman art, obesity often
      assumed the characteristics of caricature and of satire, confirmed by the
      elaboration of the stereotype of the sponger. Obesity generated irony and
      sarcasm; meanwhile the figure of the tyrant too was modelled on the physical type
      of the obesus, in whom the vice both of alimentary and sexual excess was
      concentrated. The evaluation of obesity, in the course of the time, has seen
      alternate phases, that propose different physical models and elaborate different
      aesthetical canons, but always closely related to a strong social factor as a
      distinctive sign: opulence. Nowadays obesity is seen, on the contrary, as an ever
      increasing nutritional disorder, both in prevalence and in incidence, and, to the
      ideal of the fat subject, very recent years have progressively substituted a
      different aesthetic typology, also because hyperalimentation has been qualified
      as a concomitant cause for a number of degenerative disorders.

PMID- 15722989
TI  - Caroli's syndrome. A case report and review of the literature.
AB  - Personal experience in the treatment of a female patient presenting a pure
      monolobar Caroli's disease, is described. The woman was asymptomatic so far;
      during the last 2 weeks she was admitted on 3 occasions with repeated attacks of
      cholangitis and obstructive jaundice. Surgery was performed for relief of the
      jaundice. A diagnosis of segmental Caroli's disease (congenital dilatation of
      intrahepatic bile ducts) with congenital fibrosis was made on the basis of marked
      fibrous septa with the characteristic ductal plate formation on left hepatectomy
      specimen and the cysts seen on ultrasound.

PMID- 15722990
TI  - A woman with a long history of abdominal pain.

PMID- 15722991
TI  - Focused assessment with sonography for trauma (FAST): what it is, how it is
      carried out, and why we disagree.

PMID- 15722993
TI  - Diagnostic applications of cardiac multislice CT with sixteen-row scanner: state
      of the art.
AB  - Coronary angiography is nowadays the diagnostic standard in the evaluation of
      coronary artery anatomy, in the identification of stenoses and in the follow-up
      of revascularization procedures (PTCA-stenting, bypass). The limitations of such
      technique in terms of invasivity and high cost has targeted research efforts
      towards the development of non invasive diagnostic tools. Technological evolution
      in the field of helical CT has provided 2, 4, 8 and 16 detector-row multislice
      scanners characterized by progressive improvements in terms of spatial and
      temporal resolution that have made them increasingly suitable for the analysis of
      moving structures with high quality anatomic detail. The main cardiologic
      applications of multislice CT include coronary calcium scoring, the evaluation of
      coronary vascular anatomy and disease, follow-up of revascularization procedures
      (stenting, bypass), and the evaluation of cardiac walls and chambers. The aim of
      this paper is to describe the applications of sixteen detector-row multisclice CT
      in non invasive evaluation of cardiac and coronary diseases.

PMID- 15722992
TI  - Real-time, contrast-enhanced sonographic imaging in emergency radiology.
AB  - PURPOSE: To report our pilot experience in the evaluation of traumatic and
      nontraumatic emergencies with contrast-specific, continuous-mode sonography (US)
      and a second-generation contrast medium. MATERIALS AND METHODS: Between January
      2002 and December 2003 we evaluated 126 acute patients by using real-time
      contrast-specific US: blunt abdominal trauma (76 cases), penetrating abdominal
      trauma (3), blunt scrotal trauma (1), right upper abdominal pain (10), left upper
      abdominal pain (9), epigastric pain (2), flank pain (5), right lower abdominal
      pain (2), scrotal pain (7), postoperative abdominal sepsis (1), post-biopsy
      haemorrhage (1), ruptured abdominal aortic aneurysm (8), postsurgical aortic
      bleeding (1). In all cases the radiologist performed a complete baseline US
      survey and then decided whether or not to add a contrast-enhanced examination.
      RESULTS: All contrast-enhanced sonographic studies were completed proving to be
      adequate for diagnostic purposes and without adverse reactions to contrast
      medium. There were 40 true negatives. The final diagnosis, obtained in 85
      positive cases out of 86, was: splenic injury (28 cases), hepatic injury (3),
      renal injury (3), multiple injuries (3), pancreatic and portal vein injury (1),
      colonic-mesocolic injury (1), testicular trauma (1), hepatic abscess (9), hepatic
      ischaemia (1), gangrenous cholecystitis (1), splenic infarction (8), splenic
      haematoma abscess (1), renal infection (4), renal infarction (1), necrotizing
      pancreatitis (1), post-biopsy haemorrhage (1), appendicitis (2), peritoneal
      abscesses (1), testicular torsion (6), orchiepididymitis (1), iliac artery
      dissection (1), ruptured abdominal aortic aneurysm (6), aortic periprosthetic
      hemorrhage (1). Out of 85 positive cases, agreement between baseline US and
      contrast-specific US was absent in 8% of cases, low in 26%, intermediate in 42%,
      and high in 24%. Baseline US had 3 false positives. Relevance of contrast
      specific US was absent in 17% of cases, low (additional data not relevant for
      patient management) in 26%, intermediate (relevant additional data not modifying
      patient management) in 34%, and high (additional data modifying patient
      management) in 23%. Agreement between contrast-specific US and the gold standards
      was absent in 0% of cases, low in 6%, intermediate in 38%, and high in 56%.
      Contrast-specific US had 2 false positive results. CONCLUSIONS: Real-time
      contrast-specific US is an effective technique in emergency imaging. Its role
      should not be considered as a replacement of CT (though in some instances it can
      be considered a valuable alternative) but as a useful integration of conventional
      US. By always having the opportunity to add contrast-enhanced imaging, in case of
      interpretation doubts or diagnostic difficulties, the radiologist can assess the
      emergency patient with improved confidence and skill.

PMID- 15722994
TI  - Thoracic cardiovascular imaging with 16-row multislice Computed Tomography and
      retrospective ECG-gating. Technical note.
AB  - PURPOSE: To apply the retrospective ECG-gating to the 16-row MSCT scan of
      intrathoracic vessels. MATERIALS AND METHODS: Fourty-eight patients underwent
      MSCT with a new 16-row scanner (Sensation 16-Siemens) for the study of the great
      intrathoracic vessels. In group 1 (33 patients) a retrospectively ECG-gated
      protocol was applied; in the control-group 2 (15 patients) a conventional MSCT
      protocol for thoracic imaging was applied. Images were scored regarding 1) the
      presence or absence of artefacts determined by breath-hold, beam hardening and
      mis-triggering; 2) the visualisation (optimal, mild and poor) of great
      intrathoracic vessels (aorta, pulmonary arteries and veins); 3) the visualisation
      (presence or absence) of proximal, mid and distal coronary arteries (left main,
      left anterior descending, circumflex, and right coronary artery). RESULTS:
      Ascending aorta showed motion artefacts in 3 (20%) cases in group 2 and none in
      group 1. In group 1, proximal LAD, CX, and RCA were assessable in 94%, 91%, and
      91%, respectively. Left main coronary artery was assessable in 32 (97%) and 10
      (67%) cases for group 1 and 2, respectively. In group 2, proximal segments of
      left anterior descending (LAD), circumflex (CX), and right coronary artery (RCA),
      were almost not assessable. CONCLUSIONS: The retrospectively ECG-gated 16-row
      MSCT provides more information regarding ascending aorta and coronary arteries.

PMID- 15722995
TI  - Virtual stenting of iliac arteries: a new technique for choosing stents and stent
      grafts by means of 3D rotational angiography. Preliminary data.
AB  - PURPOSE: Virtual stenting (VS) is a new tool in the 3D processing work station of
      rotational angiography (RA) systems. This tool enables the 3D visualization of a
      stent or stent-graft in the site of a stenotic, obstructive or aneurysmatic
      lesion to be treated. We report the preliminary results obtained with this
      software in the treatment of segmental stenotic, obstructive or aneurysmal
      lesions of the iliac artery. MATERIALS AND METHODS: Seventeen patients under-went
      rotational angiography and 3D reformations for one or more stenoses (19 cases),
      obstructive lesions (2 cases) or aneurysms (2 cases) of the common and/or
      external iliac artery and were treated with stents in 22/23 of cases. In all
      cases, the VS tool was applied to the stenotic-obstructive lesion on the
      identified on the 3D angiogram obtained before the stenting procedure. RESULTS:
      The measurements of the stents/stents-grafts (length, proximal and distal
      diameter) provided by the tool were compared to those of the stent deployed. In
      22/23 procedures, the measurements of virtual stenting and those of the deployed
      stent showed a good level of concordance. The system failed to provide correct
      measurements in only one long and tortuous iliac aneurysm. CONCLUSIONS: The
      ''virtual stenting'' tool proved to be reliable and fast, and enabled a more
      objective selection of the stent to be deployed on a stenotic-obstructive lesion
      in almost all cases. In cases of aneurysms of marked tortuosity, the system tends
      to suggest an inappropriate stent. The possibility of manually defining the
      optimal stent path within the aneurysmal sac might be useful.

PMID- 15722996
TI  - Tibial plateau fractures: evaluation with multidetector-CT.
AB  - PURPOSE: To evaluate the role of Multislice CT (MSCT) in classifying tibial
      plateau fractures and deciding on the appropriate therapeutic treatment compared
      to conventional radiology. MATERIALS AND METHODS: Twenty-five patients with a
      clinical diagnosis of tibial plateau fracture were studied with plain film and
      MSCT. The CT images were reconstructed with MPR and 3D technique and the
      fractures classified according to the Swiss AO-ASIF classification. The following
      radiographic and CT parameters were used: fracture location and size, number of
      fragments or degree of depression of fracture; plateau area involved; surgical
      access; degree of osteoporosis and bone tissue loss. RESULTS: The plain film and
      MSCT classification showed agreement in 48% of cases and disagreement in 52%.
      MSCT better demonstrated disruption of the tibial plateau surface and showed a
      larger number of fragments. In 60% of patients the CT features led the
      orthopaedist to modify the treatment. In three patients CT demonstrated bone
      tissue loss, suggesting for bone graft. In four patients CT showed alteration of
      the bone architecture and suggested the use of different material for
      osteosynthesis. Compared to axial CT, the MSCT MPR and 3D reconstructions enabled
      a more accurate assessment of plateau depression, and of rotation and separation
      of the fragments. The 3D technique proved better than MPR in evaluating rotation
      of fractured fragments as it provides an overall view as well as the possibility
      of rotating the bone segments. CONCLUSIONS: MSCT and 3D reconstructions are very
      useful for classifying tibial plateau fractures and for preoperative assessment.
      Patients with clinical evidence of fracture might benefit from an examination
      with CT instead of conventional radiology.

PMID- 15722997
TI  - Radiology and adult celiac disease. Current indications of small bowel barium
      examinations.
AB  - PURPOSE: To evaluate the current role of small bowel (SB) radiologic barium
      examinations in adult celiac disease (ACD). MATERIALS AND METHODS: Retrospective
      review of 61 SB barium examinations in 280 ACD patients. Sixty-one examinations
      in 61 patients were performed: 7/61 with small bowel ''follow-through'' (SBFT)
      method, and 54/61 with small bowel double-contrast enteroclysis (SBE).
      Radiological criteria for ACD diagnosis were divided in four groups: 1) definite
      ACD (reversal of jejuno-ileal fold pattern); 2) possible ACD (malabsorption
      pattern and ileal jejunization); 3) malabsorption (fluid, dilatation,
      ''moulage'', flocculation); 4) complicated ACD (irregular, thickened, nodular
      folds; wall thickening; masses). RESULTS: In 49/61 patients RX examinations were
      performed before ACD diagnosis. In this group, clinical presentations included
      one or more of the following: diarrhea, weight loss, malabsorption, anemia,
      abdominal pain; 7/49 had a SBFT, and 42/49 a SBE. All 7 SBFTs showed pattern 3,
      and 8/42 SBEs showed pattern 2 (suspected ACD). In 34/42 patients SBE allowed a
      definite ACD diagnosis (pattern 1); however, 6/34 were also false-positive for
      complicated ACD (pattern 4). Ten out of sixty-one patients were clinically
      suspected of having complicated ACD, correctly excluded (8/8) or confirmed (2/2)
      by SBE. None of these 59/61 patients had a radiologic diagnosis of normal' SB.
      The last 2/61 patients with ACD, examined for persisting chronic anemia, had a
      normal SBE. CONCLUSIONS: This study confirm that SB radiology may be of value
      either in ACD diagnosis or in excluding complications: SBE is currently the most
      accurate examination. SBE alone is however less accurate in confirming
      complicated ACD; further imaging techniques are always needed in this clinical
      context.

PMID- 15722998
TI  - Percutaneous treatment of simple renal cysts with sclerotherapy and extended
      drainage.
AB  - PURPOSE: To present the long-term results of sclerotherapy of symptomatic simple
      renal cysts with alcohol and aethoxysclerol followed by protracted seven-day
      drainage and to compare the efficacy of the two sclerosing agents used in the
      therapy. MATERIALS AND METHODS: Sixty-six symptomatic patients underwent
      percutaneous treatment with drainage and sclerotherapy of 72 simple renal cysts
      in a day hospital setting. The cysts were divided into two groups according to
      size (Group I and Group II with cyst volume smaller or larger than 600 ml
      respectively) for a better comparison of the results. The cysts were punctured
      directly under local anaesthesia with a 7 French Trocar catheter using the ''one
      shot'' technique and ultrasound guidance; a pig tail catheter was then left in
      the cyst for the complete evacuation of the cyst fluid. Sclerotherapy was
      performed by injection of 95% alcohol or 3% aethoxysclerol for 40 minutes,
      followed by seven-day drainage. On the basis of dimensional criteria, response to
      treatment was defined as: recovery, partial recurrence or recurrence. RESULTS:
      The procedure was successful in 97.2% of the cases with regard to cyst drainage,
      with clinical recovery in 95.3% of the cases. Group I had 14 recoveries and no
      complete recurrence after either alcohol or aethoxysclerol, 2 partial recurrences
      with alcohol and 4 partial recurrences with aethoxysclerol; Group II had 15
      recoveries, 14 partial recurrences and one complete recurrence with alcohol, and
      5 recoveries, 8 partial recurrences and 2 complete recurrences with
      aethoxysclerol. CONCLUSIONS: The one-shot technique under ultrasound guidance
      prevents the risk of major complications, reduces the likelihood of failure and
      is inexpensive; furthermore, it significantly reduces procedure time and is
      better tolerated by patients. On the basis of the clinical and dimensional
      results obtained, percutaneous sclerotherapy of renal cysts can be recommended as
      the treatment of choice and as a valid alternative to laparoscopy. As for the
      comparison between the two sclerosing agents, alcohol has a higher cost and
      negative side effects, but is more effective for the treatment of larger cysts.
      Aethoxysclerol is less expensive and has no side effects, but tends to lead to
      septic complications. On the basis of our experience, we therefore recommend the
      use of aethoxysclerol for sclerotherapy of smaller cysts followed by a 4-day
      drainage. For larger cysts, we recommend repeated alcoholization and the removal
      of the drainage catheter after seven days.

PMID- 15722999
TI  - Prostate cancer: evaluation with endorectal MR imaging and three-dimensional
      proton MR spectroscopic imaging.
AB  - PURPOSE: To establish the additional value of MR Spectroscopy (3D CSI MRS Three
      dimensional Chemical Shift Imaging Magnetic Resonance Spectroscopy) to endorectal
      MR in the diagnosis and grading of prostate cancer. MATERIALS AND METHODS: MR and
      3D CSI MR spectroscopy were performed in 53 patients with suspicion of prostate
      cancer on the basis of rectal exploration and/or transrectal ultrasound and/or
      the PSA levels. All the examinations were performed with a 1.5 T imager using an
      endorectal coil. We acquired axial and coronal T2-weighted FSE sequences, axial
      T1-weighted SE sequences and PRESS 3D CSI (Point Resolved Spectroscopy 3D
      Chemical Shift Imaging) sequences localized on the axial T2 images so as to
      include the prostatic gland while excluding the periprostatic fat. The MR
      examinations were evaluated by two radiologists unaware of the clinical data,
      transrectal ultrasound findings, PSA levels and histological findings. The MR and
      3D CSI MRS findings were compared with the biopsy findings in 22 cases and with
      material obtained from laparoscopic prostatectomy in 31 cases. RESULTS: The
      histological examination revealed adenocarcinoma in 37 cases, prostatitis in 2
      cases and no alterations in the remaining 14 cases. The morphologic MR scan
      showed a sensitivity of 76%, a specificity of 56%, an accuracy of 70%, a PPV of
      80% and a NPV of 50%. By combining MR and 3D CSI MRS we obtained a sensitivity of
      95%, a specificity of 81%, an accuracy of 91%, a PPV of 92% and a NPV of 87%.
      Elevated choline concentrations were found both in tumours with a low Gleason
      score (18 cases) and in those with a high Gleason score (19 cases); instead we
      found markedly reduced (n=9) or absent (n=4) citrate only in the tumours with a
      high Gleason score, while we found normal citrate levels in the 18 tumours with a
      low Gleason score. CONCLUSIONS: The 3D CSI MRS improved the reliability of
      endorectal MR in the diagnosis and characterisation of prostatic cancer.
      Moreover, the 3D CSI MRS findings demonstrated a linear correlation with tumour
      grade.

PMID- 15723000
TI  - Teleradiology system accessible through a common web browser.
AB  - PURPOSE: To describe a teleradiology system accessible via a PC and a common web
      browser. MATERIAL AND METHODS: A dedicated system is connected to several
      radiological imagers (DR, US, CT, MR) with DICOM standard and TCP/IP protocol.
      The images are visualised in a common web browser on a remote PC by connecting to
      the dedicated web-site. Compressed images are visualised on a web page. Special
      toolbars allow specific operations to be performed on the images (brightness
      contrast, zoom, distance measurement and ROI defining) and the communication with
      the radiological centre. RESULTS: The graphic interface is user-friendly and does
      not require any special knowledge, except for basic PC and internet surfing.
      Image compression can be set to preserve image quality, and image transfer is
      fast. CONCLUSIONS: The system presented overcomes the limitations of conventional
      teleradiology systems since it requires no special network or dedicated software,
      allowing for visualisation of a radiological examination on a PC and a common web
      browser.

PMID- 15723001
TI  - Electron beam dosimetry of Total Skin Electron Therapy (TSET).
AB  - Total Skin Electron Therapy (TSET) was carried out using an electron beam with a
      nominal energy of 6 MeV. The beam was adequately filtered and angled in order to
      create dual fields. The uniformity of the dose distribution to the patient was
      10%. The relative dosimetry of the dual beam was performed using a silicon diode
      and an ionization chamber in a standard water phantom. X-Omat V films were
      irradiated in a cylindrical PMMA phantom in order to obtain the dose distribution
      for the six TSET dual fields used in the treatment. Absolute dosimetry was
      carried out with a calibrated ionization chamber placed in a cylindrical water
      phantom. The dose contribution per monitor unit of the single dual beams was
      determined with this method.

PMID- 15723002
TI  - Evaluation of the efficacy of a bismuth shield during CT examinations.
AB  - PURPOSE: The purpose of the study was to evaluate the efficacy of a bismuth
      shield (Attenurad F&L Medical Products, Vandergrift, PA) in reducing the dose to
      surface organs during Computed Tomography (CT) examinations. The shield was
      evaluated for reduction of the dose to breast during chest examinations and
      reduction of the dose to the lens of the eye during brain examinations. MATERIALS
      AND METHODS: The dose was measured on patients (10 for the eye and 30 for the
      breast), and on an anthropomorphic phantom (Alderson Rando). The reduction of
      image quality was evaluated both qualitatively by an expert radiologist, and in
      terms of increased noise on the phantom images (Rando). RESULTS: The use of the
      protective device reduced the dose by 34% to the breast and 50% to the lens.
      These figures are confirmed by the measurements taken both on patients and on the
      anthropomorphic phantom. The protective device reduced image quality in the
      regions immediately beneath it, but in the cases considered, those regions were
      of no diagnostic interest, while in the brain and lung regions, the quality is
      only slightly reduced, always allowing a correct diagnostic evaluation. Numerical
      analysis also led to the conclusion that a modest increase in noise is only
      statistically significant for the anterior portions of the lung. When present,
      the artifacts appeared outside the field of clinical interest. That is mainly due
      to the use of a foam pad (0.7 - 1 cm thick) to protect the breast. DISCUSSION AND
      CONCLUSIONS: The protection proved effective both in the case of breast and of
      lens, leading to a significant reduction in dose, without excessively affecting
      image quality. The shield proved easy to use, and did not increase the
      examination time.

PMID- 15723003
TI  - ["Breast charter 2004". Diagnostic approach to breast pathology].

PMID- 15723004
TI  - Gln48His is the prevalent myocilin mutation in primary open angle and primary
      congenital glaucoma phenotypes in India.
AB  - PURPOSE: Myocilin gene defects have been originally implicated in primary open
      angle glaucoma (POAG). Based on multiple reports for the occurrence of Gln48His
      mutation (c.144G>T; HGMD accession number CM023962) among Indian POAG patients,
      we wanted to estimate the prevalence of this mutation in primary open angle and
      primary congenital glaucoma (PCG) in India and assess its role in the causation
      of the disease. METHODS: Two hundred cases each of POAG and PCG were screened for
      the Gln48His mutation by RFLP (AccI) analysis of the PCR amplicons followed by
      confirmation of the c.144G>T change by direct sequencing. RESULTS: The Gln48His
      mutation was detected in 9 different glaucoma patients (four POAG and five PCG).
      While all four POAG cases were heterozygous, among PCG cases, four were
      heterozygous and one exhibited homozygous genotype for the mutation. One each of
      POAG and PCG patients was detected to be heterozygous for CYP1B1 mutation
      (c.1656C>T, Pro437Leu) and (c.1449G>A, Arg368His), respectively. None of the 300
      ethnically matched normal controls contained either the MYOC or CYP1B1
      mutation(s). CONCLUSIONS: The myocilin mutation, Gln48His, represents an allelic
      condition involving a spectrum of glaucoma phenotypes in Indian populations, and
      could be a potential risk factor towards disease predisposition among patients of
      Indian origin. The study also highlights the role of MYOC as a candidate in
      different glaucoma subtypes that needs to be investigated further.

PMID- 15723005
TI  - Genomic structure and organization of the high grade Myopia-2 locus (MYP2)
      critical region: mutation screening of 9 positional candidate genes.
AB  - PURPOSE: Myopia is a common complex eye disorder, with implications for blindness
      due to increased risk of retinal detachment, chorioretinal degeneration,
      premature cataracts, and glaucoma. A genomic interval of 2.2 centiMorgans (cM)
      was defined on chromosome band 18p11.31 using 7 families diagnosed with autosomal
      dominant high myopia and was designated the MYP2 locus. To characterize this
      region, we analyzed 9 known candidate genes localized to within the 2.2 cM
      interval by direct sequencing. METHODS: Using public databases, a physical map of
      the MYP2 interval was compiled. Gene expression studies in ocular tissues using
      complementary DNA library screens, microarray experiments, reverse transcription
      techniques, and expression data identified in external databases aided in
      prioritizing gene selection for screening. Coding regions, intron-exon boundaries
      and untranslated exons of all known genes [Clusterin-like 1 (CLUL1), elastin
      microfibril interfacer 2 (EMILIN2), lipin 2 (LPIN2), myomesin 1 (MYOM1), myosin
      regulatory light chain 3 (MRCL3), myosin regulatory light chain 2 (MRLC2),
      transforming growth beta-induced factor (TGIFbeta), large Drosophila homolog
      associated protein 1 (DLGAP1), and zinc finger protein 161 homolog (ZFP161)] were
      sequenced using genomic DNA samples from 9 affected and 6 unaffected MYP2
      pedigree members, and from 5 external controls (4 unaffected and 1 affected).
      Gene sequence changes were compared to known variants from public single
      nucleotide polymorphism (SNP) databases. RESULTS: In total, 103 polymorphisms
      were found by direct sequencing; 10 were missense, 14 were silent, 26 were not
      translated, 49 were intronic, 1 insertion, and 3 were homozygous deletions.
      Twenty-seven polymorphisms were novel. Novel SNPs were submitted to the public
      database; observed frequencies were submitted for known SNPs. No sequence
      alterations segregated with the disease phenotype. CONCLUSIONS: Mutation analysis
      of 9 encoded positional candidate genes on MYP2 loci did not identify sequence
      alterations associated with the disease phenotype. Further studies of MYP2
      candidate genes, including analysis of putative genes predicted in silico, are
      underway.

PMID- 15723006
TI  - Management of early deep infection after rotator cuff repair surgery.
AB  - Deep soft-tissue infection occurs infrequently after rotator cuff repair surgery.
      We retrospectively reviewed the clinical presentation in 14 patients whose
      rotator cuff repair was complicated by an early deep infection (<6 weeks). The
      functional outcome after treatment in 12 of these patients was analyzed at a mean
      follow-up of 37.5 months (range, 11-122 months). The diagnosis of infection was
      most often made within 3 weeks from the date of surgery (mean, 18 days; range, 3
      41 days). Common presenting symptoms included localized wound erythema and
      drainage. The blood leukocyte counts were usually normal, but the erythrocyte
      sedimentation rates and C-reactive protein levels were elevated. A mean of 2.6
      surgical debridements were required to clean the wound effectively in each case.
      Eight of twelve patients were dissatisfied at final assessment. Most patients
      reported reasonably good relief of pain, but they had residual shoulder stiffness
      and weakness. Retention of suture anchors in the humeral head did not preclude
      successful eradication of the infection.

PMID- 15723007
TI  - Heterotopic ossification after primary shoulder arthroplasty.
AB  - We have assessed the incidence of heterotopic ossification (HO) after primary
      shoulder joint replacement in 126 shoulders; 58 patients had hemiarthroplasty,
      and 68 had total shoulder joint replacement. HO developed to a minor extent in
      15% of patients (19/126). There was no statistical difference between
      hemiarthroplasty or total shoulder replacement or between male and female
      patients. Patients with cuff tear arthropathy were the only group with an
      increased risk (36.4% [4/11]) of having HO develop. In patients with
      osteoarthritis, fractures, or rheumatoid arthritis, HO occurred in less than
      14.5% (15/115). Nonsteroidal anti-inflammatory drugs (NSAIDs) did not appear to
      have any effect on HO as in hip replacement, as HO developed in 15.15% of
      patients having NSAIDs postoperatively and in 15.05% of patients without NSAIDs.
      Prophylaxis of HO with NSAIDs seems only to be indicated in patients with cuff
      tear arthropathy.

PMID- 15723008
TI  - Quantitative assessment of thinning of the subscapularis tendon in recurrent
      anterior dislocation of the shoulder by use of magnetic resonance imaging.
AB  - It is known that thinning and lengthening of the subscapularis tendon occur in
      shoulders with recurrent anterior dislocation. However, no studies have been
      performed to quantify the morphologic changes of the subscapularis tendon under
      such conditions. We retrospectively measured the thickness and cross-sectional
      area of the subscapularis tendon by use of magnetic resonance imaging in 22
      shoulders in 11 patients with unilateral recurrent anterior dislocation of the
      shoulder. The contralateral shoulder in each patient served as a control. The
      thickness and cross-sectional area of the subscapularis on the affected side were
      smaller than those on the normal side (6.5 +/- 1.7 mm vs 8.0 +/- 1.9 mm, P =
      .001, and 388.6 +/- 120.0 mm 2 vs 547.9 +/- 128.5 mm 2 , P = .0001,
      respectively). We conclude that the subscapularis tendon undergoes an 18.7%
      decrease in thickness and a 29.1% decrease in cross-sectional area in shoulders
      with recurrent anterior dislocation.

PMID- 15723009
TI  - Intraarticular lesions in primary frozen shoulder after manipulation under
      general anesthesia.
AB  - The aim of this study was to find intraarticular lesions after manipulation under
      general anesthesia in patients with primary frozen shoulder. In a prospective
      trial conducted between 2001 and 2003 in 30 patients with primary frozen
      shoulder, the affected shoulders were manipulated while the patients were under
      general anesthetia. Exclusion criteria were secondary stiffness caused by rotator
      cuff tears and glenohumeral arthritis. After manipulation, each patient was
      examined by arthroscopy, and any intraarticular lesions were documented. In all
      patients, during manipulation, a significant improvement in the range of motion
      was achieved. Under anesthesia, flexion improved on average from 70 degrees +/-
      33 degrees to 180 degrees +/- 15 degrees, abduction from 50 degrees +/- 20
      degrees to 170 degrees +/- 25 degrees, and external rotation from -5 degrees +/-
      10 degrees to +40 degrees +/- 20 degrees. Arthroscopy revealed hemarthrosis in
      all patients after manipulation. In 22 patients, localized synovitis was detected
      in the area of the rotator interval, whereas in 8 patients, disseminated
      synovitis was observed as a feature of adhesive capsulitis. After manipulation,
      the capsule was seen to be ruptured superiorly in 11 patients, the anterior
      capsule was ruptured up to the infraglenoid pole in 24 patients, and 16 patients
      each had a capsular lesion located posteriorly. In 18 patients no additional
      joint damage was found after manipulation. In 4 patients, iatrogenic superior
      labrum anterior-posterior lesions were observed. Further injuries detected were 3
      fresh partial tears of the subscapularis tendon, 4 anterior labral detachments (1
      with a small osteochondral defect), and 2 tears of the middle glenohumeral
      ligament. Even though manipulation under anesthesia is effective in terms of
      joint mobilization, the method can cause iatrogenic intraarticular damage.

PMID- 15723010
TI  - A new clinical outcome measure of glenohumeral joint instability: the MISS
      questionnaire.
AB  - Many standard shoulder outcome measures do not adequately cover the range of
      problems and issues specifically encountered in glenohumeral joint instability
      and have been shown not to be sensitive enough to detect clinical change with
      intervention adequately. The purpose of this report is to present a prospective
      evaluation of a new self-administered patient questionnaire specifically designed
      to assess glenohumeral joint instability. The evaluation involved test-retest
      reliability and comparison with the Shoulder Rating Questionnaire (SRQ). Sixty
      four patients with confirmed glenohumeral joint instability were assessed with
      both the Melbourne Instability Shoulder Scale (MISS) and SRQ 12 preoperatively
      and at 6 months after shoulder reconstructive surgery. Twenty-two patients were
      recruited into a reliability study of the MISS questionnaire. The test-retest
      reliability of the MISS was found to be 0.98 (interclass correlation coefficient,
      mixed-model analysis of variance, absolute agreement). Assessment of agreement
      between the MISS and SRQ questionnaires indicated very poor pretest agreement
      (0.33) and moderate agreement at 6 months (0.66). The differences between the
      MISS and SRQ were statistically significant both before surgery (paired t = 13.2,
      degrees of freedom [ df ] = 63, P < .001) and at 6 months' follow-up (paired t =
      7.9, df = 63, P = .001). Change in the questionnaire scores measured from surgery
      to 6 months' follow-up was significantly greater in the MISS (mean, 30; SD, 19.1;
      median, 30.8) than in the SRQ (mean, 16.6; SD, 12.8; median, 14.3) (Wilcoxon
      test: z = -5.8, P = .0001). The results of this study show that the MISS
      questionnaire is a reliable outcome questionnaire and has a greater range to
      detect changes in shoulder instability than more global outcome questionnaires
      such as the SRQ. The higher scores encountered on the SRQ may mean that it
      underestimates the severity of a patient's instability problem.

PMID- 15723011
TI  - Results and factors affecting outcome of revision surgery for shoulder
      instability.
AB  - We conducted a clinical study identifying the causes of failure and the variables
      affecting outcome in 28 patients with failed open or arthroscopic anterior
      shoulder reconstruction for anterior glenohumeral instability. All patients
      underwent an open revision stabilization procedure. Surgical outcomes at a
      minimum 24 months' follow-up were available in 25 patients. The most common
      findings at revision surgery were capsular redundancy and Bankart lesions.
      Satisfactory results were found in 21 patients (84%) after repeat instability
      surgery. Factors contributing to negative outcome were glenohumeral arthritis,
      age greater than 30 years, 2 or more previous instability procedures, a bony
      Bankart lesion, the diagnosis of multidirectional instability, and surgery
      involving the nondominant arm (P < .05). Revision shoulder stabilization can be
      successful when the correct diagnosis is made and appropriate surgery performed.
      However, the outcome is less predictable in patients with multiple previous
      surgeries.

PMID- 15723012
TI  - Shoulder arthrodesis: indications, technique, results, and complications.
AB  - Complications after shoulder arthrodesis are frequent. Through results and
      comparisons with the literature, the presented article analyzes the correlation
      of complications with the specific operative techniques, indications, and
      postoperative treatment. Between 1964 and 2001, a total of 43 cases of shoulder
      arthrodesis (13 screw and 30 plate arthrodeses) were performed and then analyzed
      after a mean of 6.7 years (range, 0.5-36 years). Surgery was carried out on 10
      female patients (23%) and 33 male patients (77%) with a mean age of 35 years
      (range, 11-82 years). These patients had the following indications: paralysis (32
      [74%]), osteoarthritis or humeral head necrosis (15 [35%]), infection (7 [16%]),
      and persistent shoulder instability (6 [14%]). The extent of active movement
      after arthrodesis was 56 degrees abduction (range, 20 degrees - 90 degrees) and
      60 degrees forward flexion (range, 20 degrees - 105 degrees), with an increase in
      the Constant score in all cases, from a mean of 27 points preoperatively to 57
      points postoperatively (difference, 30 points). The patients rated the outcome of
      surgery as excellent, good, or satisfactory in 91% of cases. Complications after
      shoulder arthrodesis were noted in 12 of 43 patients (28%). The most frequent
      complications after screw/plate arthrodesis included pseudarthrosis, 2 (15%)/3
      (10%); infection, 1 (8%)/4 (13%); and fracture of the humerus, 0/4 (13%). No
      specific judgment can be attributed to the different osteosynthesis techniques
      used in shoulder arthrodesis, either in the cases presented at our clinic or in
      the literature. Pseudarthrosis appeared to be less frequent in cases of plate
      arthrodesis compared with screw arthrodesis. However, the application of plates
      resulted more often in infection, postoperative fractures of the humerus, and the
      necessity for removal of material. Particularly in patients with paralysis, a
      shoulder arthrodesis resulted in an improvement in postoperative active function
      and presented a suitable operative option.

PMID- 15723013
TI  - Primary stability of shoulder arthrodesis using cannulated cancellous screws.
AB  - There are no biomechanical studies available concerned with the primary stability
      of shoulder arthrodesis. The aim of our biomechanical investigations was to
      ascertain a minimal material combination with high primary stability for shoulder
      arthrodesis. For that purpose, the primary stability of 6 different forms of
      screw arthrodesis was investigated under the stress of abduction, adduction,
      anteversion, and retroversion. The mean values of the screw arthrodeses were
      compared with those of a 16-hole plate arthrodesis. All tests were carried out on
      24 human specimens without destruction by use of a materials testing machine. The
      most stable form of screw arthrodesis for the load directions of abduction,
      adduction, anteversion, and retroversion results from a specific configuration of
      screws comprising 3 horizontal humeroglenoid screws and 3 vertical acromiohumeral
      screws (318.5 +/- 99.0 N). For three forms of arthrodesis, each with 3 humerus
      glenoid screws (299.9 +/- 95.4 N), no significant difference (P = .530) was found
      compared with a 16-hole plate arthrodesis (293.4 +/- 89.3 N). The plate
      arthrodeses only achieved higher power values on abduction and adduction stress
      in comparison with screw arthrodesis with 3 humerus-glenoid screws. The
      difference was insignificant. Because arthrodesis with 3 humerus-glenoid screws
      was significantly more stable on stress of anteversion and retroversion, this
      particular screw arthrodesis is considered superior to plate arthrodeses. The use
      of the most stable form of screw arthrodesis may reduce nonunion.

PMID- 15723014
TI  - Medial oblique compression fracture of the coronoid process of the ulna.
AB  - The most widely recognized coronoid fractures have been described as occurring in
      the coronal plane according to the amount of process detached from the ulna. Over
      the last few years, we have recognized that the coronoid fracture is a much more
      complex injury than originally thought. This report calls attention to an
      oblique, medial compression fracture of the coronoid, a fracture so subtle as to
      be missed by routine assessment but sometimes associated with joint subluxation
      or dislocation. The currently accepted classification system based on a simple
      fracture pattern in the coronal plane may be too simplistic to characterize
      fractures of the coronoid fully.

PMID- 15723015
TI  - Total elbow arthroplasty failure due to overuse, C-ring failure, and/or bushing
      wear.
AB  - Semiconstrained, linked total elbow arthroplasty gives excellent functional
      results. However, the complication rate is relatively high, and complications are
      frequently significant enough to require revision surgery. The purpose of this
      study is to report on bushing wear and C-ring failure as a mid- to late-term
      complication of the Coonrad-Morrey total elbow arthroplasty. Two surgeons at
      different institutions treated 10 patients who had a previous Coonrad-Morrey
      total elbow arthroplasty and presented with C-ring and/or bushing wear. There
      were 8 men and 2 women. The mean age at the time of the initial total elbow
      arthroplasty was 54 years (range, 37-67 years). Time to revision averaged 60
      months (range, 9-156 months). Common associated factors were posttraumatic
      arthritis (3), supracondylar nonunion (5), male sex, young age, and high activity
      level. A proposed mechanism of failure is postulated.

PMID- 15723016
TI  - Displaced Mason type I fractures of the radial head and neck in adults: a fifteen
      to thirty-three-year follow-up study.
AB  - Undisplaced radial head and neck fractures are consistently described with no
      long-term deficits. The aim of this study was to evaluate specifically the long
      term outcome of displaced Mason type I fractures, which have not previously
      described. Twenty women and twelve men, with a mean age of 46 years (range, 22-69
      years) when they sustained a displaced Mason type I fracture, were reexamined at
      a mean of 21 years (range, 15-33 years) after injury. All were treated
      nonoperatively. Twenty-nine individuals had no subjective complaints, whereas
      three had occasional elbow pain. There was no objective impairment, and none had
      elbow osteoarthritis, defined as reduced joint space, whereas there was more
      radiographic degeneration in the formerly fractured elbow than in the uninjured
      elbow (85% vs 4%, P < .001). We conclude that the long-term results of
      nonoperatively treated displaced Mason type I fractures of the radial head and
      neck are predominantly favorable.

PMID- 15723017
TI  - Elbow joint laxity after experimental radial head excision and lateral collateral
      ligament rupture: efficacy of prosthetic replacement and ligament repair.
AB  - The objectives of this experimental study were to investigate the effect of
      radial head excision and lateral collateral ligament (LCL) division on elbow
      joint laxity and to determine the efficacy of radial head prosthetic replacement
      and LCL repair. Valgus, varus, internal rotation, and external rotation of the
      ulna were measured during passive flexion-extension and application of a 0.75-Nm
      torque in 6 intact cadaveric elbows and after (1) either excision of the radial
      head or division of the LCL, (2) removal of both constraints, (3) isolated radial
      head prosthetic replacement, (4) isolated LCL repair, and (5) radial head
      replacement combined with LCL repair. Isolated radial head excision increased
      varus (mean, 4.8 degrees) and external rotatory laxity (mean, 7.1 degrees), as
      did isolated LCL division (mean, 14.1 degrees for varus; mean, 14.7 degrees for
      external rotation). After removal of both constraints, varus and external
      rotatory laxities were increased by 19.0 degrees and 20.1 degrees, respectively,
      compared with the intact specimens. Isolated radial head replacement reduced mean
      varus laxity to 14.6 degrees and mean external rotatory laxity to 14.8 degrees.
      Isolated LCL repair normalized varus laxity but resulted in a 2.9 degrees
      increase in external rotatory laxity. The combined procedures restored laxity
      completely. The radial head is a constraint to varus and external rotation in the
      elbow joint, functioning by maintaining tension in the LCL. Still, removal of
      both constraints induces severe laxity, and in this case, prosthetic replacement
      may substitute for the constraining capacity of the native radial head. The
      combination of LCL repair and radial head replacement restores laxity completely,
      but an isolated LCL repair performs almost as well, probably by compensating for
      the ligamentous tension lost from radial head excision.

PMID- 15723018
TI  - Use of three-dimensional computed tomography for the analysis of the glenoid
      anatomy.
AB  - Preoperative evaluation for a total shoulder arthroplasty includes 2-dimensional
      analysis of the glenoid through either standard radiographs or computed
      tomography (CT) images. Recent evidence suggests that these 2-dimensional images
      may actually misrepresent the 3-dimensional (3D) anatomy of the glenoid. Because
      3D reconstructions of CT images allow 3D visualization and analysis of the
      scapula as a free body, we hypothesized that they can reflect the true anatomy of
      the glenoid more accurately. To test this hypothesis, we obtained various glenoid
      morphometric measurements from excised cadaveric scapulae as well as their
      respective 3D CT images. On average, the glenoid version angles measured from the
      3D CT images were within 1.0 degrees +/- 0.7 degrees (mean +/- SD) of those from
      the actual specimen (95% confidence limit, <2.2 degrees for all observers). These
      measurements from the 3D CT images showed high interobserver and intraobserver
      reliability (interobserver and intraobserver correlation coefficients, 0.983 and
      0.978, respectively). Similarly, measured glenoid surface width and length from
      the 3D CT images were within 1.8 +/- 1.2 mm and 1.4 +/- 1.1 mm, respectively, of
      those from the actual specimen. In addition, we were able to estimate the glenoid
      surface area as well as the glenoid vault volume from the 3D CT images. These
      values were 8.67 +/- 2.73 cm2 and 11.86 +/- 5.06 cm3, respectively. The mean
      glenoid vault volume with respect to its surface area was 1.35 +/- 0.24 cm3/cm2
      (range, 1.06-1.91 cm3/cm2). These data suggest that 3D CT images can accurately
      reflect the true anatomy of the glenoid and that they can provide valuable
      information regarding the glenoid surface and vault. As such, 3D CT images may
      prove to be a useful tool during the preoperative evaluation for a total shoulder
      arthroplasty, particularly in patients with significant glenoid bone loss.

PMID- 15723019
TI  - An anatomic study of the humeral insertion of the inferior glenohumeral capsule.
AB  - To define inferior humeral capsular anatomy better, 12 cadaveric shoulders were
      dissected and an inferior capsular shift was performed. Two types of inferior
      humeral attachments were identified. In 7 specimens, the anterior capsular
      insertion bifurcated at the 8-o'clock position (on a right specimen) into a
      superior internal fold adjacent to the articular cartilage and an inferior
      external fold on the humeral surgical neck. In 5 specimens, the capsular
      insertion did not split but inserted over a broad area on the surgical neck. In
      all specimens, there was a re-confluence of the two folds at the 4-o'clock
      position. The inferior humeral capsular attachment may extend as far as 2 cm
      inferior to the articular surface and can be divided into two distinct types,
      split and broad, each with distinct internal and external folds of the capsule.
      Failure to release both of these folds limits the ability to shift the capsule
      superiorly by tethering the capsule inferiorly.

PMID- 15723020
TI  - Two-part surgical neck fractures of the humerus: mechanical analysis of the
      fixation with four Shanz-type threaded pins in four different assemblies.
AB  - The configuration of percutaneous pinning may affect the stability of the
      fixation of 2-part surgical neck fractures of the humerus. In this investigation,
      the mechanical properties of four different pin configurations were analyzed by
      use of 36 fresh-frozen swine femora as an experimental model. The bones were
      selected according to previously established morphologic parameters. A transverse
      osteotomy was made in the proximal metaphyseal region of the bone, and the pins
      were inserted according to the selected configuration (group 1, four ascending
      parallel pins; group 2, three ascending parallel pins and one descending
      intersecting pin; group 3, two ascending parallel pins and two descending
      parallel intersecting pins; and group 4, two ascending parallel pins and two
      descending converging pins, on different planes [two by two]). The assemblies
      were subjected to an axial load of up to 1500 N in a universal testing machine,
      simulating a varus stress. The parameters studied were the maximum load supported
      and corresponding deformation, load and deformation at the limit of
      proportionality, rigidity, and resilience. The results showed that all
      configurations were sufficiently strong, but the maximum load and load at the
      limit of proportionality were significantly higher (P < .05) in groups 3 and 4
      (1314 and 1377 N and 950 and 923 N, respectively) than in groups 1 and 2 (1104
      and 1033 N and 738 and 777 N, respectively). Rigidity was significantly higher in
      group 3 than in groups 1 and 2 but not in group 4. Resilience, maximum
      deformation, and deformation at the limit of proportionality were not
      significantly different between groups. We conclude that the experimental model
      used was reliable for the purpose of the study and that any of the configurations
      studied would be adequate for the percutaneous fixation of 2-part surgical neck
      fractures of the humerus but group 3 configuration would be the most efficient.

PMID- 15723021
TI  - Chest wall deformity associated with osteochondroma of the scapula: a case report
      and review of the literature.

PMID- 15723022
TI  - Case report: heterotopic ossification after repair of distal biceps tendon
      rupture utilizing a single-incision Endobutton technique.

PMID- 15723023
TI  - Substance use disorder comorbidity in major depressive disorder: an exploratory
      analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort.
AB  - Patients with major depressive disorder (MDD) often present with concurrent
      substance use disorders (SUD) involving alcohol and/or illicit drugs. This
      analysis compares the depressive symptomatic presentation and a range of clinical
      and demographic features of patients with MDD and concurrent SUD symptoms vs
      those without SUD symptoms, to clarify how these two differ and to determine
      whether concurrent SUD symptoms may alter the clinical presentation of MDD. The
      first 1500 outpatients with nonpsychotic MDD enrolled in the Sequenced Treatment
      Alternatives to Relieve Depression study were divided into those with and without
      concurrent SUD symptoms as ascertained by a self-report instrument, the
      Psychiatric Diagnostic Screening Questionnaire (PDSQ). Of the 1484 cases with
      completed baseline PDSQ, 28% (n = 419) of patients with MDD were found to endorse
      symptoms consistent with current SUD. Patients with symptoms consistent with SUD
      were more likely to be men (P < .0001), to be either divorced or never married (P
      = .018), to have a younger age of onset of depression (P = .014), and to have a
      higher rate of previous suicide attempts (P = .014) than those without SUD
      symptoms. Patients with major depressive disorder who have symptoms consistent
      with SUD endorsed greater functional impairment attributable to their illness
      than those without concurrent SUD symptoms (P = .0111). The presence of SUD
      symptoms did not alter the overall depressive symptom pattern of presentation,
      except that the dual-diagnosed patients had higher levels of hypersomnia (P =
      .006), anxious mood (P = .047), and suicidal ideation (P = .036) compared to
      those without SUD symptoms. In conclusion, gender, marital status, age of onset
      of major depression, functional impairment, and suicide risk factors differ in
      depressed patients with concurrent SUD symptoms compared to those without SUD
      comorbidity.

PMID- 15723024
TI  - Effect of gender on suicide attempters versus nonattempters in an adolescent
      inpatient unit.
AB  - BACKGROUND: Although gender differences have been noted in the risk factors for
      suicide and attempted suicide, comparative studies to date have used only 2
      groups and a limited number of measures. The present study compared the effect of
      gender on suicide among 4 groups of psychiatrically hospitalized adolescents
      using a cross-sectional design. METHODS: The study sample consisted of 404
      patients, aged between 12 and 21, who were divided into 4 groups: 76 male suicide
      attempters, 103 male nonattempters, 143 female suicide attempters, and 82 female
      nonattempters. Patients were tested for life events, affective disorders,
      aggression, impulsivity, ego defense mechanisms, and death perception with the
      Child Suicide Potential Scale, Beck Depression Inventory, State-Trait Anxiety
      Inventory, Overt Aggression Scale, Multidimensional Anger Inventory, Impulsivity
      Control Scale, and Life Style Index. Findings were analyzed by multivariate
      regression with stepwise logistic models. RESULTS: Depression and anxiety were
      more prevalent in female nonattempters than in male nonattempters; there were no
      such gender differences among the attempters. Antisocial behavior was more
      prevalent in male attempters than in female attempters; there were no gender
      differences on this aspect among the nonattempters. There were gender differences
      for defense mechanisms in the attempters. Logistic regression models for men and
      women separately revealed that antisocial behavior and anxiety were common
      predictors of suicide attempt, that destructiveness was a predictor in women
      only, and that depression was associated with suicide attempt in men only.
      CONCLUSIONS: Suicide-prone female and male adolescent inpatients show distinct
      differences in psychopathology, ego defense mechanisms, and life events compared
      to psychiatrically hospitalized adolescents without any history of suicide
      attempt. Any deviation from a gender-specific behavior must raise suspicion of a
      risk of attempted suicide.

PMID- 15723025
TI  - Care satisfaction, hope, and life functioning among adults with bipolar disorder:
      data from the first 1000 participants in the Systematic Treatment Enhancement
      Program.
AB  - OBJECTIVE: The Systematic Treatment Enhancement Program for Bipolar Disorder
      (STEP-BD) is designed to evaluate the longitudinal outcome of patients with
      bipolar disorder. The STEP-BD disease-management model is built on evidence-based
      practices and a collaborative care approach designed to maximize specific and
      nonspecific treatment mechanisms. This prospective study examined the
      longitudinal relationships between patients' satisfaction with care, levels of
      hope, and life functioning in the first 1000 patients to enter STEP-BD. METHODS:
      The study used scores from the Care Satisfaction Questionnaire, Beck Hopelessness
      Scale, Range of Impaired Functioning Tool, Young Mania Rating Scale, and
      Montgomery-Asberg Depression Rating Scale at 5 time points during a 1-year
      interval. Analyses tested mediational pathways between care satisfaction, hope,
      and life functioning, depression, and mania using mixed-effects (random and
      fixed) regression models. RESULTS: Increases in care satisfaction were associated
      with decreased hopelessness (P < .01) but not related to symptoms of depression
      or mania. Similarly, decreased hopelessness was associated with better life
      functioning (P < .01) but not related to symptoms of depression or mania.
      Depression was independently associated with poorer life functioning (P < .0001).
      CONCLUSIONS: This study provided support for the hypothesized mediational pathway
      between care satisfaction, hopelessness, and life functioning. Findings suggest
      that providing care that maximizes patient hope may be important. By so doing,
      patients might overcome the learned helplessness/hopelessness that often
      accompanies a cyclical illness and build a realistic illness-management strategy.

PMID- 15723026
TI  - Study of compulsive buying in patients presenting obsessive-compulsive disorder.
AB  - OBJECTIVE: The authors assessed the prevalence of compulsive buying (CB) among
      patients presenting an obsessive-compulsive disorder (OCD). They compared the
      buying style of patients with and without CB. METHOD: One thousand five hundred
      consecutive patients were assessed by a general practitioner in Paris (France).
      Sixty patients presenting with OCD were included. Patients with CB associated
      with OCD (n = 14) were compared with those with "pure" OCD (n = 46). Sixty
      patients paired for sex and age and free from OCD, depression, and anxiety were
      also recruited among the clients of the same general practitioner. We compared 3
      groups: controls, patients with OCD, and patients with OCD + CB. RESULTS:
      Prevalence of CB was 23% (14 cases) among patients with OCD and 6% (4 cases) in
      controls (chi(2)(1) = 5.3, P = .02). Patients presenting with OCD + CB had a
      higher number of Diagnostic and Statistical Manual of Mental Disorders, Revised
      Fourth Edition diagnostic criteria for OCD than patients with pure OCD (6.1 and
      5.4, respectively, P = .001). Depression was more frequent in the OCD + CB group
      (78%) than in the OCD group (42%) and in controls (10%) (P = .02). Patients from
      the OCD + CB group had higher score at the CAGE questionnaire than those of the
      OCD group (2 vs 0.7, P = .003). Patients with OCD + CB considered 42% of their
      purchases as occasions not to be passed up compared with 15.4% in the OCD group
      and 8.6% in controls. OCD+CD patients used the items they bought after a longer
      delay than controls and patients with pure OCD (8.2 vs 3 and 3.1 days,
      respectively). CONCLUSION: Compulsive buying is more frequent in OCD than in
      controls. Patients presenting with OCD + CB show more depressive disorders and
      drink more alcohol. They are more highly implicated in the items they buy and
      they are more often disappointed by the items once they possess them.

PMID- 15723027
TI  - The childhood-onset neuropsychiatric background to adulthood psychopathic traits
      and personality disorders.
AB  - Childhood conduct disorder (CD) and adult psychopathic traits according to the
      Psychopathy Checklist Revised (PCL-R) were the closest psychiatric covariates to
      repeated violent crimes and aggression among offenders under forensic psychiatric
      investigation in Sweden. As psychopathy is not included in the present
      psychiatric diagnostic systems, we compared total and factor PCL-R scores to Axis
      I disorders, including childhood-onset neuropsychiatric disorders, and to Axis II
      personality disorders, to establish the convergence of psychopathic traits with
      other psychiatric diagnoses, and to identify possible unique features.
      Psychopathic traits were positively correlated with bipolar mood disorder and
      negatively with unipolar depression. The total PCL-R scores as well as the Factor
      2 (unemotionality) and Factor 3 (behavioral dyscontrol) scores were significantly
      correlated with attention-deficit/hyperactivity disorder, Asperger's
      syndrome/high-functioning autistic traits, CD, substance abuse, and the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Cluster B
      personality disorders. The interpersonal Factor 1 showed none of these
      correlations and may capture features that are specific to psychopathy,
      distinguishing core psychopathy from other diagnostic definitions.

PMID- 15723028
TI  - Childhood abuse, mental healthcare utilization, self-harm behavior, and multiple
      psychiatric diagnoses among inpatients with and without a borderline diagnosis.
AB  - Although borderline personality disorder (BPD) has defined diagnostic criteria, a
      number of other clinical features are associated with this diagnosis. These
      features may include childhood histories of abuse (eg, sexual, physical, and
      emotional abuse; the witnessing of violence), high mental healthcare utilization,
      self-harm behavior, and polysymptomatic presentations that result in multiple
      Axis I diagnoses. Although each of these variables has been described in the
      empirical literature, only 1 other study has explored all 4 of these variables in
      a single study population--the Collaborative Longitudinal Personality Disorders
      Study. Using clinical diagnoses and self-report surveys, we explored these
      variables among psychiatric inpatients in a community hospital. We found that,
      compared with patients with no BPD, those with BPD reported significantly more
      types of childhood trauma, higher utilization of particular mental health
      services (ie, number of times and days of hospitalization for mental health or
      substance abuse, number of psychiatrists and therapists ever seen, number of
      courses of psychotherapy treatment), and a higher number of self-harm behaviors.
      Although not significant, there were positive trends for the remaining variables.
      The authors discuss the implications of these findings as they relate to patients
      with BPD.

PMID- 15723029
TI  - Predictors of aggression on the psychiatric inpatient service.
AB  - Patients with severe mental illness are at increased risk to commit acts of
      aggression in the inpatient hospital setting. Aggressive behaviors have severe
      negative consequences for the patient, victims, clinical staff, and the
      therapeutic community as a whole. While risk factors of community and inpatient
      aggression overlap, many predictive factors diverge between the two settings. For
      example, while medication noncompliance has been a robust predictor of community
      aggression, this factor has little predictive value for inpatient settings where
      patients' pharmacotherapy is closely monitored. Relatively fewer investigators
      have examined a wide range of predictive factors associated with aggressive acts
      committed on the psychiatry inpatient service, often with conflicting results.
      The present study examined demographic, clinical, and neurocognitive performance
      predictors of self, other, object, and verbal aggressiveness in 118 acute
      inpatients. Results revealed that the arrival status at the hospital (voluntary
      vs involuntary), female gender, and substance abuse diagnosis were predictors of
      verbal aggression and aggression against others. Impaired memory functioning also
      predicted object aggression. Fewer symptoms, combined with higher cognition
      functioning, however, were significant predictors of self-aggressive acts
      committed on the inpatient service. The need for relating predictors of specific
      types of aggressiveness in schizophrenia is discussed.

PMID- 15723030
TI  - Cloninger's temperament dimensions and affective responses to different
      challenges.
AB  - Cloninger's psychobiological model of temperament and character postulates that
      each of the temperament dimensions is associated with a specific emotional
      experience, depending on the situational cues. The aim of the present study was
      to test this postulate in a variety of challenging experimental tasks. The
      participants were 91 healthy young adults whose temperament was assessed with the
      temperament and character inventory. The subjects rated their emotions during
      each task and rest period using an adjective checklist. Novelty seeking was
      associated with dullness during monotonous and aversive situations and with a
      higher level of pleasantness during the initial baseline period and the
      appetitive situation. Harm avoidance was associated with higher levels of fear
      and unpleasant emotions and lower levels of positively valenced emotions. The
      present study provides support for the validity of Cloninger's temperament
      dimensions as predictors of emotional responses during different challenges.
      Especially, novelty seeking and harm avoidance appear to have a significant
      influence on emotional experience.

PMID- 15723031
TI  - Do daughters with eating disorders agree with their parents' perception of family
      functioning?
AB  - OBJECTIVE: The current study compared the perceptions of family functioning
      between daughters with eating disorders (EDs) and their parents. This
      investigation was an expansion of the Fornari et al (Compr Psychiatry 1999;40:434
      441) study, which investigated the relationship between the perceived family
      functioning and depressive symptoms in individuals with ED patients receiving
      outpatient services. METHOD: One hundred twenty-six female subjects, ranging in
      age from 13 to 34 years (mean 18.3 years) completed the Beck Depression Inventory
      (BDI) (Arch Gen Psychiatry 1961;4:561-571) and the Family Assessment Device (FAD)
      (J Marital Fam Ther 1983;9:171-180) on admission to an outpatient ED program. The
      patient's parent(s) (118 mothers and 96 fathers) also completed the FAD. Eating
      disorder subgroup diagnosis and major depressive disorder diagnosis were
      established according to the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition , criteria, using the Schedule for Affective Disorders
      and Schizophrenia-Lifetime (Arch Gen Psychiatry 1987;35:837-844). Repeated
      measures analysis of covariance was performed comparing family members on each of
      the 7 subscales of the FAD with BDI entered as the covariate. RESULTS:
      Statistically significant differences were found between patient and parental
      perceptions of overall family functioning. Mothers rated family functioning as
      significantly healthier and less chaotic than their daughters did. There were
      fewer significant differences between maternal and paternal perceptions of family
      functioning, and no significant differences between fathers' and daughters'
      perceptions of the family. Eating disorder diagnosis did not contribute to these
      differences in perception of family functioning. In addition, high self-reported
      depressive symptoms of the daughters were related to the perception of high
      family dysfunction for all 3 informants; depressive symptoms did not, however,
      alter the differences in perception between family members. DISCUSSION:
      Differences in viewpoints between parents and daughters regarding the family
      environment may contribute to the continuation of a dysfunctional family pattern
      and maintenance of the ED and/or impact negatively on the course of treatment.
      Possible implications for treatment are discussed, particularly because of the
      differences of the mothers' views. The results of this study strongly support the
      importance of including the patient's family in the initial evaluation,
      regardless of the patient's age.

PMID- 15723032
TI  - Discriminant efficiency of antisocial and borderline personality disorder
      criteria in Hispanic men with substance use disorders.
AB  - The authors examined the discriminant efficiency of the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition ( DSM-IV ) criteria for
      borderline personality disorder (BPD) and antisocial personality disorder (APD).
      Subjects were 74 men admitted to an outpatient substance abuse program for
      monolingual Hispanic adults. All were reliably assessed with the Spanish-language
      version of the Diagnostic Interview for DSM-IV Personality Disorders. Conditional
      probabilities were calculated to determine the diagnostic efficiency and
      discriminant efficiency of BPD and APD symptoms. Twenty-five (34%) subjects met
      diagnostic criteria for BPD, and 16 (22%) met criteria for APD. The diagnostic co
      occurrence of these disorders was statistically significant. Whereas the
      diagnostic efficiency of the BPD criterion set was comparable to that reported in
      other clinical studies, these criteria were not significantly more efficient in
      diagnosing BPD than APD. By contrast, the APD criteria were more efficient in
      diagnosing APD than BPD; this was true for both the "adult" and the "conduct
      disorder" APD criterion subsets. In male Hispanic outpatients with substance use
      disorders, BPD and APD show significant diagnostic overlap. The APD criteria are
      useful in discriminating these 2 disorders, whereas the BPD criteria are not.
      These findings have implications for the discriminant validity of the BPD and APD
      criteria and support the value of the conduct disorder criteria in predicting APD
      in adulthood.

PMID- 15723033
TI  - Persistent hallucinosis in borderline personality disorder.
AB  - A case series of 10 patients with a diagnosis of borderline personality disorder
      (BPD) presenting with auditory hallucinosis is examined. In this series, the
      hallucinations were persistent, longstanding, and a significant source of
      distress and disability. Extrapolating from this series to our sample of 171
      patients with BPD suggests that a form of auditory hallucinosis may occur in
      almost 30% of this population. The failure to emphasize this phenomenon in
      current systems of classification risks misdiagnosis or inappropriate treatment.
      Use of terms such as pseudohallucination or quasi hallucination dismisses the
      phenomenon as unimportant or as "not real." There is an emerging literature on
      the frequency of hallucinosis among nonpatients. A basis for understanding
      different forms of hallucination is discussed with reference to the concept of
      "normativity." We propose a nomenclature for hallucinosis that is expressed in
      positive terms, reflecting the clinical significance of the phenomenon in
      different contexts: (1) normative hallucinosis, (2) traumatic-intrusive
      hallucinosis (as in our series), (3) psychotic hallucinosis, and (4) organic
      hallucinosis.

PMID- 15723034
TI  - A case of seasonal bipolar disorder exacerbated by Cushing's disease.
AB  - While depression is common in Cushing's syndrome from whatever cause (pituitary,
      adrenal, or ectopic adrenocorticotropic hormone-secreting tumor or hyperplasia,
      or exogenous administration of glucocorticoids) and hypercortisolemia is
      prevalent in major depression, any association between seasonal affective
      disorder and Cushing's syndrome is unknown. We present a case of seasonal bipolar
      disorder, gradually worsening for more than 9 years (1985-1994), accompanied by
      increasing osteoporosis, mild weight gain, and slight truncal obesity in a middle
      aged woman. In January 1991, her seasonal affective disorder was successfully
      treated with light therapy, but in the following year, bipolar mood swings with a
      seasonal pattern emerged, which were refractory to light therapy and
      antidepressants but responsive to lithium. In August 1992, she became depressed
      despite a 1500-mg lithium daily dosage along with light therapy, and, in 1993, a
      diagnosis of Cushing's disease (Cushing's syndrome as a result of a pituitary
      adrenocorticotropic hormone-secreting tumor) was made. The pituitary tumor was
      removed in February 1994, and pituitary function was fully restored by 1996.
      While the symptoms of Cushing's syndrome subsided, her bipolar illness continued
      to require maintenance treatment with low doses of lithium but did not require
      light therapy.

PMID- 15723035
TI  - The adolescent and substance abuse: current concepts.

PMID- 15723038
TI  - Resolution of severe macular oedema in adult Coat's syndrome with high-dose
      intravitreal triamcinolone acetonide.
AB  - OBJECTIVE: To report the clinical outcome of a patient who received high-dose
      intravitreal triamcinolone acetonide as treatment for severe macular oedema
      secondary to adult Coat's syndrome. METHOD: Case report. RESULTS: A 74-year-old
      Indian man complaining of chronic gradual blurring of vision in the left eye was
      found to have adult Coat's syndrome with severe macular oedema. He received 25 mg
      of intravitreal triamcinolone acetonide following unsuccessful resolution with
      grid laser. Optical coherence tomography (OCT) demonstrated up to 75% decrease in
      macular oedema that was evident even after 9 months follow-up. However, there was
      no significant improvement in visual acuity. CONCLUSION: Intravitreal
      triamcinolone is a reasonable option in reducing severe macular oedema in cases
      of adult Coat's syndrome.

PMID- 15723037
TI  - Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP.
AB  - The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an important
      role in the development of breast carcinomas. This orphan receptor is efficiently
      downregulated by the unusual co-repressor SHP and has been thought to be ligand
      independent. We present the crystal structure at a resolution of 1.9 A of the
      ligand-binding domain of hLRH-1 in complex with the NR box 1 motif of human SHP,
      which we find contacts the AF-2 region of hLRH-1 using selective structural
      motifs. Electron density indicates phospholipid bound within the ligand-binding
      pocket, which we confirm using mass spectrometry of solvent-extracted samples. We
      further show that pocket mutations reduce phospholipid binding and receptor
      activity in vivo. Our results indicate that hLRH-1's control of gene expression
      is mediated by phospholipid binding, and establish hLRH-1 as a novel target for
      compounds designed to slow breast cancer development.

PMID- 15723039
TI  - Intravitreal triamcinolone acetonide for treatment of persistent macular oedema
      in branch retinal vein occlusion.
AB  - BACKGROUND: To evaluate the efficacy of intravitreal triamcinolone acetonide
      injection on persistent macular oedema in branch retinal vein occlusion that
      fails to respond to previous laser photocoagulation. MATERIAL AND METHODS: A
      total of 19 eyes of 19 patients with persistent macular oedema due to branch
      retinal vein occlusion were treated with 8 mg/0.2 ml of intravitreal
      triamcinolone acetonide injection. The main outcome measures included best
      corrected visual acuity, intraocular pressure, and macular oedema map values of
      Heidelberg Retinal Tomograph II (HRT II) before and after intravitreal
      triamcinolone injection. RESULTS: The mean follow-up time was 6.2+/-1.0 months.
      The mean baseline best-corrected logarithm of minimal angle of resolution
      (LogMAR) value for visual acuities of the patients before intravitreal
      triamcinolone injection was 1.01+/-0.16. After treatment, it was 0.55+/-0.22 at
      the 1-month, 0.56+/-0.22 at 3-month, and 0.62+/-0.22 at the last visits and the
      differences were statistically significant when compared with baseline values
      (for each, P<0.001). The mean oedema map values on HRT II significantly decreased
      by 28.5% at 1-month, 23.8% at 3-month, and 23.8% at the last visit when compared
      with preinjection values (for each, P<0.001). Intraocular pressure elevation
      exceeding 21 mmHg was observed in 26.3% of eyes at 1-month, 15.7% at 3-month, and
      5.2% at the last visit, but was controlled with topical anti-glaucomatous
      medications in all eyes. CONCLUSION: Intravitreal triamcinolone acetonide
      application is a promising approach in the treatment of persistent macular oedema
      due to branch retinal vein occlusion non-respondent to laser photocoagulation.

PMID- 15723040
TI  - An Arabidopsis aspartic protease functions as an anti-cell-death component in
      reproduction and embryogenesis.
AB  - The components and pathways that regulate and execute developmental cell death
      programmes in plants remain largely unknown. We have found that the PROMOTION OF
      CELL SURVIVAL 1 (PCS1) gene in Arabidopsis, which encodes an aspartic protease,
      has an important role in determining the fate of cells in embryonic development
      and in reproduction processes. The loss-of-function mutation of PCS1 causes
      degeneration of both male and female gametophytes and excessive cell death of
      developing embryos. Conversely, ectopic expression of PCS1 causes the septum and
      stomium cells that normally die in the anther wall to survive instead, leading to
      a failure in anther dehiscence and male sterility. PCS1 provides a new avenue for
      understanding the mechanisms of the programmed cell death processes that are
      associated with developmental pathways in plants and makes available a useful
      tool for engineering the male sterility trait for hybrid seed production.

PMID- 15723041
TI  - Resetting of peripheral circadian clock by prostaglandin E2.
AB  - In mammals, the master circadian pacemaker is located in the suprachiasmatic
      nucleus (SCN) of the hypothalamus. The SCN is thought to drive peripheral
      oscillators by controlling neuronal and humoral signals that can entrain the
      peripheral clocks. Here, we show that prostaglandin E2 (PGE2), a proinflammatory
      compound known to have diverse biological effects, is able to act as an in vivo
      clock-resetting agent. We find that in cultured NIH3T3 fibroblasts, PGE2 is able
      to induce transient expression of Period 1 messenger RNA and the following
      circadian oscillation of clock gene expression. Furthermore, we demonstrate that
      intraperitoneal administration of PGE2 results in the phase shift of circadian
      gene expression in mouse peripheral tissues in a time-dependent manner. This
      phase shift is also induced by the EP1/EP3 agonist sulprostone but not by the EP2
      agonist butaprost. The PGE2-induced phase shift is inhibited by the EP1
      antagonist SC-51322. These results suggest that PGE2 acts as an in vivo clock
      resetting factor by means of the EP1 subtype of PGE receptors.

PMID- 15723042
TI  - The cellular level of telomere dysfunction determines induction of senescence or
      apoptosis in vivo.
AB  - Telomere dysfunction induces two types of cellular response: cellular senescence
      and apoptosis. We analysed the extent to which the cellular level of telomere
      dysfunction and p53 gene status affect these cellular responses in mouse liver
      using the experimental system of TRF2 inhibition by a dominant-negative version
      of the protein (TRF2delta B delta M). We show that the level of telomere
      dysfunction correlates with the level of TRF2delta B delta M protein expression
      resulting in chromosomal fusions, aberrant mitotic figures and aneuploidy of
      liver cells. These alterations provoked p53-independent apoptosis, but a strictly
      p53-dependent senescence response in distinct populations of mouse liver cells
      depending on the cellular level of TRF2delta B delta M expression. Apoptosis was
      associated with higher expression of TRF2delta B delta M, whereas cellular
      senescence was associated with low levels of TRF2delta B delta M) expression. Our
      data provide experimental evidence that induction of senescence or apoptosis in
      vivo depends on the cellular level of telomere dysfunction and differentially on
      p53 gene function.

PMID- 15723043
TI  - Glycoprotein-specific ubiquitin ligases recognize N-glycans in unfolded
      substrates.
AB  - Misfolded or unassembled polypeptides in the endoplasmic reticulum (ER) are retro
      translocated into the cytosol and degraded by the ubiquitin-proteasome system. We
      reported previously that the SCF(Fbs1,2) ubiquitin-ligase complexes that
      contribute to ubiquitination of glycoproteins are involved in the ER-associated
      degradation pathway. Here we investigated how the SCF(Fbs1,2) complexes interact
      with unfolded glycoproteins. The SCF(Fbs1) complex was associated with p97/VCP
      AAA ATPase and bound to integrin-beta1, one of the SCF(Fbs1) substrates, in the
      cytosol in a manner dependent on p97 ATPase activity. Both Fbs1 and Fbs2 proteins
      interacted with denatured glycoproteins, which were modified with not only high
      mannose but also complex-type oligosaccharides, more efficiently than native
      proteins. Given that Fbs proteins interact with innermost chitobiose in N
      glycans, we propose that Fbs proteins distinguish native from unfolded
      glycoproteins by sensing the exposed chitobiose structure.

PMID- 15723044
TI  - The SNARE Ykt6 is released from yeast vacuoles during an early stage of fusion.
AB  - The farnesylated SNARE (N-ethylmaleimide-sensitive factor attachment protein
      receptor) Ykt6 mediates protein palmitoylation at the yeast vacuole by means of
      its amino-terminal longin domain. Ykt6 is localized equally to membranes and the
      cytosol, although it is unclear how this distribution is mediated. We now show
      that Ykt6 is released efficiently from vacuoles during an early stage of yeast
      vacuole fusion. This release is dependent on the disassembly of vacuolar SNAREs
      (priming). In recent literature, it had been demonstrated for mammalian Ykt6 that
      the membrane-bound form is both palmitoylated and farnesylated at its carboxy
      terminal CAAX box, whereas soluble Ykt6 is only farnesylated. In agreement with
      this, we find that yeast Ykt6 becomes palmitoylated in vitro at its C-terminal
      CAAX motif. Mutagenesis of the potential palmitoylation site in yeast Ykt6
      prevents stable membrane association and is lethal. On the basis of these and
      other findings, we speculate that Ykt6 is released from membranes by
      depalmitoylation. Such a mechanism could enable recycling of this lipid-anchored
      SNARE from the vacuole independent of retrograde transport.

PMID- 15723045
TI  - Microfabricated arrays of femtoliter chambers allow single molecule enzymology.
AB  - Precise understanding of biological functions requires tools comparable in size
      to the basic components of life. Single molecule studies have revealed molecular
      behaviors usually hidden in the ensemble- and time-averaging of bulk experiments.
      Although most such approaches rely on sophisticated optical strategies to limit
      the detection volume, another attractive approach is to perform the assay inside
      very small containers. We have developed a silicone device presenting a large
      array of micrometer-sized cavities. We used it to tightly enclose volumes of
      solution, as low as femtoliters, over long periods of time. The microchip insures
      that the chambers are uniform and precisely positioned. We demonstrated the
      feasibility of our approach by measuring the activity of single molecules of beta
      galactosidase and horseradish peroxidase. The approach should be of interest for
      many ultrasensitive bioassays at the single-molecule level.

PMID- 15723046
TI  - Directed evolution of human T-cell receptors with picomolar affinities by phage
      display.
AB  - Peptides derived from almost all proteins, including disease-associated proteins,
      can be presented on the cell surface as peptide-human leukocyte antigen (pHLA)
      complexes. T cells specifically recognize pHLA with their clonally rearranged T
      cell receptors (TCRs), whose natural affinities are limited to approximately 1
      100 muM. Here we describe the display of ten different human TCRs on the surface
      of bacteriophage, stabilized by a nonnative interchain disulfide bond. We report
      the directed evolution of high-affinity TCRs specific for two different pHLAs:
      the human T-cell lymphotropic virus type 1 (HTLV-1) tax(11-19) peptide-HLA
      A(*)0201 complex and the NY-ESO-1(157-165) tumor-associated peptide antigen-HLA
      A(*)0201 complex, with affinities of up to 2.5 nM and 26 pM, respectively, and we
      demonstrate their high specificity and sensitivity for targeting of cell-surface
      pHLAs.

PMID- 15723047
TI  - Programmable ligand-controlled riboregulators of eukaryotic gene expression.
AB  - Recent studies have demonstrated the importance of noncoding RNA elements in
      regulating gene expression networks. We describe the design of a class of small
      trans-acting RNAs that directly regulate gene expression in a ligand-dependent
      manner. These allosteric riboregulators, which we call antiswitches, are made
      fully tunable and modular by rational design. They offer flexible control
      strategies by adopting active or inactive forms in response to ligand binding,
      depending on their design. They can be tailor-made to regulate the expression of
      target transcripts in response to different cellular effectors. Coupled with in
      vitro selection technologies for generating nucleic acid ligand-binding species,
      antiswitches present a platform for programming cellular behavior and genetic
      networks with respect to cellular state and environmental stimuli.

PMID- 15723048
TI  - Generation of high-affinity human antibodies by combining donor-derived and
      synthetic complementarity-determining-region diversity.
AB  - Combinatorial libraries of rearranged hypervariable V(H) and V(L) sequences from
      nonimmunized human donors contain antigen specificities, including anti-self
      reactivities, created by random pairing of V(H)s and V(L)s. Somatic hypermutation
      of immunoglobulin genes, however, is critical in the generation of high-affinity
      antibodies in vivo and occurs only after immunization. Thus, in combinatorial
      phage display libraries from nonimmunized donors, high-affinity antibodies are
      rarely found. Lengthy in vitro affinity maturation is often needed to improve
      antibodies from such libraries. We report the construction of human Fab libraries
      having a unique combination of immunoglobulin sequences captured from human
      donors and synthetic diversity in key antigen contact sites in heavy-chain
      complementarity-determining regions 1 and 2. The success of this strategy is
      demonstrated by identifying many monovalent Fabs against multiple therapeutic
      targets that show higher affinities than approved therapeutic antibodies. This
      very often circumvents the need for affinity maturation, accelerating discovery
      of antibody drug candidates.

PMID- 15723049
TI  - Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for
      cell cycle and size control.
AB  - The mammalian target of rapamycin (mTOR) and Akt proteins regulate various steps
      of muscle development and growth, but the physiological relevance and the
      downstream effectors are under investigation. Here we show that S6 kinase 1
      (S6K1), a protein kinase activated by nutrients and insulin-like growth factors
      (IGFs), is essential for the control of muscle cytoplasmic volume by Akt and
      mTOR. Deletion of S6K1 does not affect myoblast cell proliferation but reduces
      myoblast size to the same extent as that observed with mTOR inhibition by
      rapamycin. In the differentiated state, S6K1(-/-) myotubes have a normal number
      of nuclei but are smaller, and their hypertrophic response to IGF1, nutrients and
      membrane-targeted Akt is blunted. These growth defects reveal that mTOR requires
      distinct effectors for the control of muscle cell cycle and size, potentially
      opening new avenues of therapeutic intervention against neoplasia or muscle
      atrophy.

PMID- 15723050
TI  - Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell
      invasion.
AB  - Actomyosin contractility is a mechanism by which cells exert locomotory force
      against their environment. Signalling downstream of the small GTPase Rho
      increases contractility through Rho-kinase (ROCK)-mediated regulation of myosin
      II light chain (MLC2) phosphorylation. Cdc42 signalling has been shown to control
      cell polarity. Tumour cells can move through a three-dimensional matrix with
      either a rounded morphology characterized by Rho-ROCK dependence or with an
      elongated morphology characterized by Rho-ROCK independence. Here we show that
      contractility necessary for elongated morphology and invasion can be generated by
      Cdc42-MRCK signalling. MRCK (myotonic dystrophy kinase-related Cdc42-binding
      kinase) cooperates with ROCK in the maintenance of elongated morphology and
      invasion and either MRCK or ROCK is sufficient for MLC2 phosphorylation, through
      the inhibitory phosphorylation of myosin phosphatase. By contrast, in rounded
      ROCK-dependent movement, where MLC2 phosphorylation is higher, MRCK has a smaller
      role. Our data show that a Cdc42-MRCK signal mediates myosin-dependent cell
      motility and highlight convergence between Rho and Cdc42 signalling.

PMID- 15723051
TI  - PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs
      STEF/Tiam1.
AB  - A polarity complex of PAR-3, PAR-6 and atypical protein kinase C (aPKC) functions
      in various cell-polarization events, including neuron specification. The small
      GTPase Cdc42 binds to PAR-6 and regulates cell polarity. However, little is known
      about the downstream signals of the Cdc42-PAR protein complex. Here, we found
      that PAR-3 directly interacted with STEF/Tiam1, which are Rac-specific guanine
      nucleotide-exchange factors, and that STEF formed a complex with PAR-3-aPKC-PAR-6
      Cdc42-GTP. Cdc42 induces lamellipodia in a Rac-dependent manner in N1E-115
      neuroblastoma cells. Disruption of Cdc42-PAR-6 or PAR-3-STEF binding inhibited
      Cdc42-induced lamellipodia but not filopodia. The isolated STEF-binding PAR-3
      fragment was sufficient to induce lamellipodia independently of Cdc42 and PAR-6.
      PAR-3 is required for Cdc42-induced Rac activation, but is not essential for
      lamellipodia formation itself. In cultured hippocampal neurons, STEF accumulated
      at the tip of the growing axon and colocalized with PAR-3. The spatio-temporal
      activation and signalling of Cdc42-PAR-6-PAR-3-STEF/Tiam1-Rac seem to be involved
      in neurite growth and axon specification. We propose that the PAR-6-PAR-3 complex
      mediates Cdc42-induced Rac activation by means of STEF/Tiam1, and that this
      process seems to be required for the establishment of neuronal polarity.

PMID- 15723052
TI  - Par-3 controls tight junction assembly through the Rac exchange factor Tiam1.
AB  - The par (partitioning-defective) genes express a set of conserved proteins that
      function in polarization and asymmetric cell division. Par-3 has multiple protein
      interaction domains, and associates with Par-6 and atypical protein kinase C
      (aPKC). In Drosophila, Par-3 is essential for epithelial cell polarization.
      However, its function in mammals is unclear. Here we show that depletion of Par-3
      in mammalian epithelial cells profoundly disrupts tight junction assembly.
      Expression of a carboxy-terminal fragment plus the third PDZ domain of Par-3
      partially rescues junction assembly, but neither Par-6 nor aPKC binding is
      required. Unexpectedly, Rac is constitutively activated in cells lacking Par-3,
      and the assembly of tight junctions is efficiently restored by a dominant
      negative Rac mutant. The Rac exchange factor Tiam1 (ref. 7) binds directly to the
      carboxy-terminal region of Par-3, and knockdown of Tiam1 enhances tight junction
      formation in cells lacking Par-3. These results define a critical function for
      Par-3 in tight junction assembly, and reveal a novel mechanism through which Par
      3 engages in the spatial regulation of Rac activity and establishment of
      epithelial polarity.

PMID- 15723053
TI  - c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription.
AB  - The c-Myc oncoprotein regulates transcription of genes that are associated with
      cell growth, proliferation and apoptosis. c-Myc levels are modulated by
      ubiquitin/proteasome-mediated degradation. Proteasome inhibition leads to c-Myc
      accumulation within nucleoli, indicating that c-Myc might have a nucleolar
      function. Here we show that the proteins c-Myc and Max interact in nucleoli and
      are associated with ribosomal DNA. This association is increased upon activation
      of quiescent cells and is followed by recruitment of the Myc cofactor TRRAP,
      enhanced histone acetylation, recruitment of RNA polymerase I (Pol I), and
      activation of rDNA transcription. Using small interfering RNAs (siRNAs) against c
      Myc and an inhibitor of Myc-Max interactions, we demonstrate that c-Myc is
      required for activating rDNA transcription in response to mitogenic signals.
      Furthermore, using the ligand-activated MycER (ER, oestrogen receptor) system, we
      show that c-Myc can activate Pol I transcription in the absence of Pol II
      transcription. These results suggest that c-Myc coordinates the activity of all
      three nuclear RNA polymerases, and thereby plays a key role in regulating
      ribosome biogenesis and cell growth.

PMID- 15723054
TI  - c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by
      RNA polymerase I.
AB  - c-Myc coordinates cell growth and division through a transcriptional programme
      that involves both RNA polymerase (Pol) II- and Pol III-transcribed genes. Here,
      we demonstrate that human c-Myc also directly enhances Pol I transcription of
      ribosomal RNA (rRNA) genes. rRNA synthesis and accumulation occurs rapidly
      following activation of a conditional MYC-ER allele (coding for a Myc-oestrogen
      receptor fusion protein), is resistant to inhibition of Pol II transcription and
      is markedly reduced by c-MYC RNA interference. Furthermore, by using combined
      immunofluorescence and rRNA-FISH, we have detected endogenous c-Myc in nucleoli
      at sites of active ribosomal DNA (rDNA) transcription. Our data also show that c
      Myc binds to specific consensus elements located in human rDNA and associates
      with the Pol I-specific factor SL1. The presence of c-Myc at specific sites on
      rDNA coincides with the recruitment of SL1 to the rDNA promoter and with
      increased histone acetylation. We propose that stimulation of rRNA synthesis by c
      Myc is a key pathway driving cell growth and tumorigenesis.

PMID- 15723055
TI  - Myc-dependent regulation of ribosomal RNA synthesis during Drosophila
      development.
AB  - Regulating ribosome number is thought to control cellular growth. Synthesis of
      ribosomal RNA (rRNA) is a limiting step in ribosome biogenesis and rates of rRNA
      synthesis are generally altered depending on the growth status of a cell.
      Although studies in unicellular systems have addressed the mechanisms by which
      this occurs, few studies have applied a genetic approach to examine growth
      dependent control of rRNA synthesis in metazoans. Here, we show that in
      Drosophila melanogaster Myc (dMyc) is a regulator of rRNA synthesis. Expression
      of dMyc is both necessary and sufficient to control rRNA synthesis and ribosome
      biogenesis during larval development. Stimulation of rRNA synthesis by dMyc is
      mediated through a rapid, coordinated increase in the levels of the Pol I
      transcriptional machinery. In addition, the growth effects of dMyc in larval wing
      imaginal discs require de novo rRNA synthesis. We suggest that during animal
      development, the control of rRNA synthesis and ribosome biogenesis is an
      essential Myc function.

PMID- 15723056
TI  - Functionally distinct kinesin-13 family members cooperate to regulate microtubule
      dynamics during interphase.
AB  - Regulation of microtubule polymerization and depolymerization is required for
      proper cell development. Here, we report that two proteins of the Drosophila
      melanogaster kinesin-13 family, KLP10A and KLP59C, cooperate to drive microtubule
      depolymerization in interphase cells. Analyses of microtubule dynamics in S2
      cells depleted of these proteins indicate that both proteins stimulate
      depolymerization, but alter distinct parameters of dynamic instability; KLP10A
      stimulates catastrophe (a switch from growth to shrinkage) whereas KLP59C
      suppresses rescue (a switch from shrinkage to growth). Moreover,
      immunofluorescence and live analyses of cells expressing tagged kinesins reveal
      that KLP10A and KLP59C target to polymerizing and depolymerizing microtubule plus
      ends, respectively. Our data also suggest that KLP10A is deposited on
      microtubules by the plus-end tracking protein, EB1. Our findings support a model
      in which these two members of the kinesin-13 family divide the labour of
      microtubule depolymerization.

PMID- 15723057
TI  - Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2
      protein is critical for Golgi secretory function.
AB  - The level of diacylglycerol (DAG) in the Golgi apparatus is crucial for protein
      transport to the plasma membrane. Studies in budding yeast indicate that Sec14p,
      a phosphatidylinositol (PI)-transfer protein, is involved in regulating DAG
      homeostasis in the Golgi complex. Here, we show that Nir2, a peripheral Golgi
      protein containing a PI-transfer domain, is essential for maintaining the
      structural and functional integrity of the Golgi apparatus in mammalian cells.
      Depletion of Nir2 by RNAi leads to substantial inhibition of protein transport
      from the trans-Golgi network to the plasma membrane, and causes a reduction in
      the DAG level in the Golgi apparatus. Remarkably, inactivation of cytidine
      [corrected] 5'-diphosphate (CDP)-choline pathway for phosphatidylcholine
      biosynthesis restores both effects. These results indicate that Nir2 is involved
      in maintaining a critical DAG pool in the Golgi apparatus by regulating its
      consumption via the CDP-choline pathway, demonstrating the interface between
      secretion from the Golgi and lipid homeostasis.

PMID- 15723058
TI  - Restoration of spatial working memory by genetic rescue of GluR-A-deficient mice.
AB  - Gene-targeted mice lacking the AMPA receptor subunit GluR-A (also called GluR1
      encoded by the gene Gria1,) have deficits in hippocampal CA3-CA1 long-term
      potentiation (LTP) and have profoundly impaired hippocampus-dependent spatial
      working memory (SWM) tasks, although their spatial reference memory remains
      normal. Here we show that forebrain-localized expression of GFP-tagged GluR-A
      subunits in GluR-A-deficient mice rescues SWM, paralleling its rescue of CA3-CA1
      LTP. This provides powerful new evidence linking hippocampal GluR-A-dependent
      synaptic plasticity to rapid, flexible memory processing.

PMID- 15723059
TI  - Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating
      gating and rectification.
AB  - N- and C-terminal cytoplasmic domains of inwardly rectifying K (Kir) channels
      control the ion-permeation pathway through diverse interactions with small
      molecules and protein ligands in the cytoplasm. Two new crystal structures of the
      cytoplasmic domains of Kir2.1 (Kir2.1(L)) and the G protein-sensitive Kir3.1
      (Kir3.1(S)) channels in the absence of PIP(2) show the cytoplasmic ion-permeation
      pathways occluded by four cytoplasmic loops that form a girdle around the central
      pore (G-loop). Significant flexibility of the pore-facing G-loop of Kir2.1(L) and
      Kir3.1(S) suggests a possible role as a diffusion barrier between cytoplasmic and
      transmembrane pores. Consistent with this, mutations of the G-loop disrupted
      gating or inward rectification. Structural comparison shows a di-aspartate
      cluster on the distal end of the cytoplasmic pore of Kir2.1(L) that is important
      for modulating inward rectification. Taken together, these results suggest the
      cytoplasmic domains of Kir channels undergo structural changes to modulate gating
      and inward rectification.

PMID- 15723060
TI  - Multiple periods of functional ocular dominance plasticity in mouse visual
      cortex.
AB  - The precise period when experience shapes neural circuits in the mouse visual
      system is unknown. We used Arc induction to monitor the functional pattern of
      ipsilateral eye representation in cortex during normal development and after
      visual deprivation. After monocular deprivation during the critical period, Arc
      induction reflects ocular dominance (OD) shifts within the binocular zone. Arc
      induction also reports faithfully expected OD shifts in cat. Shifts towards the
      open eye and weakening of the deprived eye were seen in layer 4 after the
      critical period ends and also before it begins. These shifts include an
      unexpected spatial expansion of Arc induction into the monocular zone. However,
      this plasticity is not present in adult layer 6. Thus, functionally assessed OD
      can be altered in cortex by ocular imbalances substantially earlier and far later
      than expected.

PMID- 15723061
TI  - Hierarchical and asymmetric temporal sensitivity in human auditory cortices.
AB  - Lateralization of function in auditory cortex has remained a persistent puzzle.
      Previous studies using signals with differing spectrotemporal characteristics
      support a model in which the left hemisphere is more sensitive to temporal and
      the right more sensitive to spectral stimulus attributes. Here we use single
      trial sparse-acquisition fMRI and a stimulus with parametrically varying
      segmental structure affecting primarily temporal properties. We show that both
      left and right auditory cortices are remarkably sensitive to temporal structure.
      Crucially, beyond bilateral sensitivity to timing information, we uncover two
      functionally significant interactions. First, local spectrotemporal signal
      structure is differentially processed in the superior temporal gyrus. Second,
      lateralized responses emerge in the higher-order superior temporal sulcus, where
      more slowly modulated signals preferentially drive the right hemisphere. The data
      support a model in which sounds are analyzed on two distinct timescales, 25-50 ms
      and 200-300 ms.

PMID- 15723062
TI  - Preserved spatial memory after hippocampal lesions: effects of extensive
      experience in a complex environment.
AB  - Damage to the hippocampus typically impairs spatial learning and memory in
      animals, but humans with hippocampal lesions retain spatial memories of
      premorbidly familiar environments. We showed that, like humans, normal rats
      reared in a complex environment and then given hippocampal lesions retained
      allocentric spatial memory for that environment. These results, which ruled out
      dependency on single cues, landmarks or specific routes, suggest that extensive
      premorbid experience leads to spatial representations that are independent of the
      hippocampus.

PMID- 15723063
TI  - Fine-scale recombination patterns differ between chimpanzees and humans.
AB  - Recombination rates seem to vary extensively along the human genome. Pedigree
      analysis suggests that rates vary by an order of magnitude when measured at the
      megabase scale, and at a finer scale, sperm typing studies point to the existence
      of recombination hotspots. These are short regions (1-2 kb) in which
      recombination rates are 10-1,000 times higher than the background rate. Less is
      known about how recombination rates change over time. Here we determined to what
      degree recombination rates are conserved among closely related species by
      estimating recombination rates from 14 Mb of linkage disequilibrium data in
      central chimpanzee and human populations. The results suggest that recombination
      hotspots are not conserved between the two species and that recombination rates
      in larger (50 kb) genomic regions are only weakly conserved. Therefore, the
      recombination landscape has changed markedly between the two species.

PMID- 15723064
TI  - Transcription control reprogramming in genetic backup circuits.
AB  - A key question in molecular genetics is why severe mutations often do not result
      in a detectably abnormal phenotype. This robustness was partially ascribed to
      redundant paralogs that may provide backup for one another in case of mutation.
      Mining mutant viability and mRNA expression data in Saccharomyces cerevisiae, we
      found that backup was provided predominantly by paralogs that are expressed
      dissimilarly in most growth conditions. We considered that this apparent
      inconsistency might be resolved by a transcriptional reprogramming mechanism that
      allows the intact paralog to rescue the organism upon mutation of its
      counterpart. We found that in wild-type cells, partial coregulation across growth
      conditions predicted the ability of paralogs to alter their transcription
      patterns and to provide backup for one another. Notably, the sets of regulatory
      motifs that controlled the paralogs with the most efficient backup activity
      deliberately overlapped only partially; paralogs with highly similar or
      dissimilar sets of motifs had suboptimal backup activity. Such an arrangement of
      partially shared regulatory motifs reconciles the differential expression of
      paralogs with their ability to back each other up.

PMID- 15723065
TI  - Global assessment of promoter methylation in a mouse model of cancer identifies
      ID4 as a putative tumor-suppressor gene in human leukemia.
AB  - DNA methylation is associated with malignant transformation, but limitations
      imposed by genetic variability, tumor heterogeneity, availability of paired
      normal tissues and methodologies for global assessment of DNA methylation have
      limited progress in understanding the extent of epigenetic events in the
      initiation and progression of human cancer and in identifying genes that undergo
      methylation during cancer. We developed a mouse model of T/natural killer acute
      lymphoblastic leukemia that is always preceded by polyclonal lymphocyte expansion
      to determine how aberrant promoter DNA methylation and consequent gene silencing
      might be contributing to leukemic transformation. We used restriction landmark
      genomic scanning with this mouse model of preleukemia reproducibly progressing to
      leukemia to show that specific genomic methylation is associated with only the
      leukemic phase and is not random. We also identified Idb4 as a putative tumor
      suppressor gene that is methylated in most mouse and human leukemias but in only
      a minority of other human cancers.

PMID- 15723066
TI  - Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome
      and interacts with RPGR and calmodulin.
AB  - Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal
      failure in children. Identification of four genes mutated in NPHP subtypes 1-4
      (refs. 4-9) has linked the pathogenesis of NPHP to ciliary functions. Ten percent
      of affected individuals have retinitis pigmentosa, constituting the renal-retinal
      Senior-Loken syndrome (SLSN). Here we identify, by positional cloning, mutations
      in an evolutionarily conserved gene, IQCB1 (also called NPHP5), as the most
      frequent cause of SLSN. IQCB1 encodes an IQ-domain protein, nephrocystin-5. All
      individuals with IQCB1 mutations have retinitis pigmentosa. Hence, we examined
      the interaction of nephrocystin-5 with RPGR (retinitis pigmentosa GTPase
      regulator), which is expressed in photoreceptor cilia and associated with 10-20%
      of retinitis pigmentosa. We show that nephrocystin-5, RPGR and calmodulin can be
      coimmunoprecipitated from retinal extracts, and that these proteins localize to
      connecting cilia of photoreceptors and to primary cilia of renal epithelial
      cells. Our studies emphasize the central role of ciliary dysfunction in the
      pathogenesis of SLSN.

PMID- 15723067
TI  - Immune activation modulates hematopoiesis through interactions between CD27 and
      CD70.
AB  - The differentiation of hematopoietic stem cells into mature blood cell lineages
      is tightly regulated. Here we report that CD27, which is expressed on stem and
      early progenitor cells in bone marrow, can be important in this process. Deletion
      of CD27 increased the myeloid colony-forming potential of stem and early
      progenitor cells and enhanced B lymphoid reconstitutive capacity in competitive
      transplantation experiments. Conversely, stimulation of CD27(+) progenitor cells
      with CD70, the unique ligand for CD27, inhibited colony-forming potential in
      vitro and lymphocyte outgrowth in vivo. As CD70 is expressed only on activated
      immune cells, we suggest that CD27 triggering on early progenitor cells provides
      a negative feedback signal to leukocyte differentiation during immune activation.

PMID- 15723071
TI  - Contribution of bone marrow-derived endothelial cells to human tumor vasculature.
AB  - It has been shown that bone marrow-derived stem cells can form a major fraction
      of the tumor endothelium in mouse tumors. To determine the role of such cells in
      human tumor angiogenesis, we studied six individuals who developed cancers after
      bone marrow transplantation with donor cells derived from individuals of the
      opposite sex. By performing fluorescence in situ hybridization (FISH) with sex
      chromosome-specific probes in conjunction with fluorescent antibody staining, we
      found that such stem cells indeed contributed to tumor endothelium, but at low
      levels, averaging only 4.9% of the total. These results illustrate substantial
      differences between human tumors and many mouse models with respect to
      angiogenesis and have important implications for the translation of experimental
      antiangiogenic therapies to the clinic.

PMID- 15723072
TI  - G-CSF prevents cardiac remodeling after myocardial infarction by activating the
      Jak-Stat pathway in cardiomyocytes.
AB  - Granulocyte colony-stimulating factor (G-CSF) was reported to induce myocardial
      regeneration by promoting mobilization of bone marrow stem cells to the injured
      heart after myocardial infarction, but the precise mechanisms of the beneficial
      effects of G-CSF are not fully understood. Here we show that G-CSF acts directly
      on cardiomyocytes and promotes their survival after myocardial infarction. G-CSF
      receptor was expressed on cardiomyocytes and G-CSF activated the Jak/Stat pathway
      in cardiomyocytes. The G-CSF treatment did not affect initial infarct size at 3 d
      but improved cardiac function as early as 1 week after myocardial infarction.
      Moreover, the beneficial effects of G-CSF on cardiac function were reduced by
      delayed start of the treatment. G-CSF induced antiapoptotic proteins and
      inhibited apoptotic death of cardiomyocytes in the infarcted hearts. G-CSF also
      reduced apoptosis of endothelial cells and increased vascularization in the
      infarcted hearts, further protecting against ischemic injury. All these effects
      of G-CSF on infarcted hearts were abolished by overexpression of a dominant
      negative mutant Stat3 protein in cardiomyocytes. These results suggest that G-CSF
      promotes survival of cardiac myocytes and prevents left ventricular remodeling
      after myocardial infarction through the functional communication between
      cardiomyocytes and noncardiomyocytes.

PMID- 15723073
TI  - The fibrin-derived peptide Bbeta15-42 protects the myocardium against ischemia
      reperfusion injury.
AB  - In the event of a myocardial infarction, current interventions aim to reopen the
      occluded vessel to reduce myocardial damage and injury. Although reperfusion is
      essential for tissue salvage, it can cause further damage and the onset of
      inflammation. We show a novel anti-inflammatory effect of a fibrin-derived
      peptide, Bbeta15-42. This peptide competes with the fibrin fragment N-terminal
      disulfide knot-II (an analog of the fibrin E1 fragment) for binding to vascular
      endothelial (VE)-cadherin, thereby preventing transmigration of leukocytes across
      endothelial cell monolayers. In acute or chronic rat models of myocardial
      ischemia-reperfusion injury, Bbeta15-42 substantially reduces leukocyte
      infiltration, infarct size and subsequent scar formation. The pathogenic role of
      fibrinogen products is further confirmed in fibrinogen knockout mice, in which
      infarct size was substantially smaller than in wild-type animals. Our findings
      conclude that the interplay of fibrin fragments, leukocytes and VE-cadherin
      contribute to the pathogenesis of myocardial damage and reperfusion injury. The
      naturally occurring peptide Bbeta15-42 represents a potential candidate for
      reperfusion therapy in humans.

PMID- 15723074
TI  - EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter
      leukodystrophy.
AB  - Vanishing white matter disease (VWM) is a heritable leukodystrophy linked to
      mutations in translation initiation factor 2B (eIF2B). Although the clinical
      course of this disease has been relatively well described, the cellular
      consequences of EIF2B mutations on neural cells are unknown. Here we have
      established cell cultures from the brain of an individual with VWM carrying
      mutations in subunit 5 of eIF2B (encoded by EIF2B5). Despite the extensive
      demyelination apparent in this VWM patient, normal-appearing oligodendrocytes
      were readily generated in vitro. In contrast, few GFAP-expressing (GFAP+)
      astrocytes were present in primary cultures, induction of astrocytes was severely
      compromised, and the few astrocytes generated showed abnormal morphologies and
      antigenic phenotypes. Lesions in vivo also lacked GFAP+ astrocytes. RNAi
      targeting of EIF2B5 severely compromised the induction of GFAP+ cells from normal
      human glial progenitors. This raises the possibility that a deficiency in
      astrocyte function may contribute to the loss of white matter in VWM
      leukodystrophy.

PMID- 15723075
TI  - Sequence-specific potent induction of IFN-alpha by short interfering RNA in
      plasmacytoid dendritic cells through TLR7.
AB  - Short interfering RNA (siRNA) is used in RNA interference technology to avoid non
      target-related induction of type I interferon (IFN) typical for long double
      stranded RNA. Here we show that in plasmacytoid dendritic cells (PDC), an immune
      cell subset specialized in the detection of viral nucleic acids and production of
      type I IFN, some siRNA sequences, independent of their GU content, are potent
      stimuli of IFN-alpha production. Localization of the immunostimulatory motif on
      the sense strand of a potent IFN-alpha-inducing siRNA allowed dissection of
      immunostimulation and target silencing. Injection into mice of immunostimulatory
      siRNA, when complexed with cationic liposomes, induced systemic immune responses
      in the same range as the TLR9 ligand CpG, including IFN-alpha in serum and
      activation of T cells and dendritic cells in spleen. Immunostimulation by siRNA
      was absent in TLR7-deficient mice. Thus sequence-specific TLR7-dependent immune
      recognition in PDC needs to be considered as an additional biological activity of
      siRNA, which then should be termed immunostimulatory RNA (isRNA).

PMID- 15723076
TI  - Structure and activity of an aminoacyl-tRNA synthetase that charges tRNA with
      nitro-tryptophan.
AB  - The most divergent of two tryptophanyl tRNA synthetases (TrpRS II) found in
      Deinococcus radiodurans interacts with a nitric oxide synthase protein that
      produces 4-nitro-tryptophan (4-NRP). TrpRS II efficiently charges transfer
      RNA(Trp) with 4-NRP and 5-hydroxy-tryptophan (5-HRP). The crystal structures of
      TrpRS II bound to tryptophan and 5-HRP reveal residue substitutions that
      accommodate modified indoles. A class of auxiliary bacterial TrpRSs conserve this
      capacity to charge tRNA with nonstandard amino acids.

PMID- 15723078
TI  - The structure of a resuscitation-promoting factor domain from Mycobacterium
      tuberculosis shows homology to lysozymes.
AB  - Resuscitation-promoting factor (RPF) proteins reactivate stationary-phase
      cultures of (G+C)-rich Gram-positive bacteria including the causative agent of
      tuberculosis, Mycobacterium tuberculosis. We report the solution structure of the
      RPF domain from M. tuberculosis Rv1009 (RpfB) solved by heteronuclear
      multidimensional NMR. Structural homology with various glycoside hydrolases
      suggested that RpfB cleaved oligosaccharides. Biochemical studies indicate that a
      conserved active site glutamate is important for resuscitation activity. These
      data, as well as the presence of a clear binding pocket for a large molecule,
      indicate that oligosaccharide cleavage is probably the signal for revival from
      dormancy.

PMID- 15723079
TI  - SUMO modification of the ubiquitin-conjugating enzyme E2-25K.
AB  - Post-translational modification with small ubiquitin-related modifier (SUMO)
      alters the function of many proteins, but the molecular mechanisms and
      consequences of this modification are still poorly defined. During a screen for
      novel SUMO1 targets, we identified the ubiquitin-conjugating enzyme E2-25K
      (Hip2). SUMO attachment severely impairs E2-25K ubiquitin thioester and
      unanchored ubiquitin chain formation in vitro. Crystal structures of E2-25K(1
      155) and of the E2-25K(1-155)-SUMO conjugate (E2-25K(*)SUMO) indicate that SUMO
      attachment interferes with E1 interaction through its location on the N-terminal
      helix. The SUMO acceptor site in E2-25K, Lys14, does not conform to the consensus
      site found in most SUMO targets (PsiKXE), and functions only in the context of an
      alpha-helix. In contrast, adjacent SUMO consensus sites are modified only when in
      unstructured peptides. The demonstration that secondary structure elements are
      part of SUMO attachment signals could contribute to a better prediction of SUMO
      targets.

PMID- 15723077
TI  - Structural basis for Diels-Alder ribozyme-catalyzed carbon-carbon bond formation.
AB  - The majority of structural efforts addressing RNA's catalytic function have
      focused on natural ribozymes, which catalyze phosphodiester transfer reactions.
      By contrast, little is known about how RNA catalyzes other types of chemical
      reactions. We report here the crystal structures of a ribozyme that catalyzes
      enantioselective carbon-carbon bond formation by the Diels-Alder reaction in the
      unbound state and in complex with a reaction product. The RNA adopts a lambda
      shaped nested pseudoknot architecture whose preformed hydrophobic pocket is
      precisely complementary in shape to the reaction product. RNA folding and product
      binding are dictated by extensive stacking and hydrogen bonding, whereas
      stereoselection is governed by the shape of the catalytic pocket. Catalysis is
      apparently achieved by a combination of proximity, complementarity and electronic
      effects. We observe structural parallels in the independently evolved catalytic
      pocket architectures for ribozyme- and antibody-catalyzed Diels-Alder carbon
      carbon bond-forming reactions.

PMID- 15723080
TI  - Delayed or delayed sequential bone marrow transplantation: relevance for acute
      graft-versus-host disease prevention after major H2 incompatible transplantation.
AB  - During this study, BalB/C mice were used as recipients and C57 bl/6 mice as
      donors. Recipients were given 800 cGys of total body irradiation (TBI) on day 0.
      Transplantation was carried out as follows: group (1): TBI on day 0; group (2):
      TBI on day 0 and transplantation on day +1; group (3): TBI on day 0 and
      transplantation on day 4; group (4): TBI on day 0 and transplantation started
      from day 4 through day 8. Mice that received TBI only died by day 11. All group 2
      mice developed aGVHD and died by day +15. In total, 70% of group 3 were still
      surviving by day 60 (P<0.001, compared to day +1 transplantation). Survival rates
      were 90% at day 60 for group 4 (P<0.001 compared to day 1 transplantation). No
      survival advantage was found between animals transplanted on day 4 and animals
      with delayed sequential transplantation (P=0.1). Significant engraftment was
      found in both groups 3 and 4, with no significant differences in the percentages
      of donor-derived cells between the two groups (P>0.05). These data demonstrate
      that either delayed or delayed sequential transplantation after TBI can be an
      effective approach for aGVHD prevention.

PMID- 15723081
TI  - The effect of interleukin-7 on the alloreactivity of human T cells depends on the
      timing of its administration in relation to the allostimulus.

PMID- 15723082
TI  - Possible role of high-dose busulfan in second reciprocal transplant between
      brother and sister for resistant acute leukemia.

PMID- 15723083
TI  - Pelvic magnetic resonance imaging after bone marrow harvest--a retrospective
      study in 50 unrelated marrow donors.
AB  - A total of 50 unrelated marrow donors were examined by pelvic magnetic resonance
      imaging (MRI) to investigate the morphological sequelae of bone marrow harvesting
      (BMH). Signal increase in T2-weighted sequences and contrast media enhancement in
      T1 sequences at the operative sites were found as typical MRI morphology 4 weeks
      after harvest (group A, n=16), corresponding to edema, hyperemia and
      proliferative activity. Although tissue repair was completed in the majority of
      donors 1 year after BMH, about 36% of donors in group B (n=16) had abnormal
      findings. These included a persistence of the 'acute injury' signal pattern
      (2/16, 12%), and signal alterations due to fatty marrow conversion (4/16, 24%).
      The proportion of MRI abnormalities increased to over 70% in two-time donors
      (group C, n=11), which might indicate a cumulation of tissue damage after
      repetitive harvests. If donors had experienced prolonged discomfort after BMH
      (group D, n=7), MRI revealed pathological signals in 86%. In conclusion, the MRI
      morphology reflects the pathophysiological reactions after BMH, including
      inflammation and tissue repair. A further prospective evaluation in a larger
      number of donors is necessary to confirm these results and to identify the
      factors which influence the extent and duration of tissue damage.

PMID- 15723084
TI  - Outcome of boost haemopoietic stem cell transplant for decreased donor chimerism
      or graft dysfunction in primary immunodeficiency.
AB  - Haemopoietic stem cell transplants (HSCT) cure increasing numbers of primary
      immunodeficiencies (PID): residual recipient T-cell function increases risk of
      incomplete or decreasing immune reconstitution, which may resolve following a
      second, unconditioned, infusion from the same donor (boost infusion). We assessed
      the outcome of 20 boost infusions in 19/139 patients transplanted for PID
      patients at our centre since 1987. Boost infusion was given 64-1226 days after
      the original HSCT. Follow-up was 4-124 months. In all, 12 of 19 patients cleared
      viral infection (6), or showed sustained increase in donor chimerism, T- and B
      cell numbers and function, or other markers (6). In 7/12 patients, immunoglobulin
      replacement has been discontinued. Four were partially successful with stable low
      level chimerism (two patients) or improved T-cell function, but not B cell
      function (two patients). Four failed with no change in donor chimerism or cell
      number. No significant association with donor source, T-cell depletion,
      conditioning regimen, boost infusion stem cell dose or time from original HSCT to
      boost was found. One patient developed grade III acute graft-versus-host disease
      despite cyclosporine, and one developed severe pneumonitis; both have recovered.
      Boost infusion was successful or partially successful in 84% of patients. The
      risk of adverse effects is low.

PMID- 15723085
TI  - Outcome of unrelated transplants in patients with multiple myeloma.
AB  - The outcome of patients with multiple myeloma treated with standard therapy is
      disappointing, with a historical median survival of 3 years. Although high-dose
      therapy with autologous stem cell transplant has improved treatment outcomes,
      cure is unlikely. Allogeneic transplant provides a tumor-free graft and a graft
      versus-myeloma effect. However, only a minority of patients has a compatible
      sibling donor. Unrelated hematopoietic stem cell transplant is another option. We
      analyzed the outcome of patients who received an unrelated bone marrow transplant
      facilitated by the National Marrow Donor Program (NMDP). Between 1989 and 2000,
      71 patients received a myeloablative unrelated transplant for multiple myeloma;
      70 patients consented for this analysis. The median recipient age was 44 years. A
      total of 31% of patients had received a prior autologous transplant. In all, 91%
      of patients engrafted. The 3-year cumulative incidence estimate of relapse was
      34+/-10%. The incidence of Grade II-IV GVHD was 47%. The Kaplan-Meier estimate
      for overall survival at 5 years was 9+/-7%. The 100-day treatment-related
      mortality was 42%. In multivariate analysis, only a male donor was a significant
      predictor for survival. Better strategies are needed to treat patients with
      multiple myeloma, perhaps by using less-toxic, nonmyeloablative conditioning
      regimens.

PMID- 15723086
TI  - How to improve the search for an unrelated haematopoietic stem cell donor. Faster
      is better than more!
AB  - Many patients do not reach haematopoietic stem cell transplantation. Shortage of
      unrelated donors (UDs) is still seen as the main cause. However, with a worldwide
      UD pool containing more than 8 million donors, it is possible that other
      impediments are becoming more important. We analysed 549 UD searches for Dutch
      patients, performed between 1987 and 2000, in order to find the reasons for
      failure or success to reach transplantation. Between 1996 and 2000, 59% of the
      patients of Northwest European origin received a graft from an UD with a median
      time span of 4.4 months from the start of the search. In all, 11% of the patients
      lacked a compatible donor, while 30% became medically unfit for transplantation.
      This is in contrast to the patients of non-Northwest European origin for whom UD
      shortage is still the most important impediment; only 32% were transplanted while
      50% lacked a compatible donor. We conclude that the shortage of donors is no
      longer the biggest constraint in unrelated stem cell transplantation for patients
      of Northwest European origin. It may be more effective to optimize the chance on
      transplantation by making the search process more efficient.

PMID- 15723087
TI  - An ex vivo model for functional studies of myofibroblasts.
AB  - Migration, proliferation and invasive growth of myofibroblasts are key cellular
      events during formation of granulation tissue in situations of wound healing,
      arteriosclerosis and tumor growth. To study the invasive phenotype of
      myofibroblasts, we established an assay where arterial tissue from chicken
      embryos was embedded in fibrin gels and stimulated with growth factors. Addition
      of serum, PDGF-BB and FGF-2, but not VEGF-A, resulted in an outgrowth of cellular
      sprouts with a pattern that was similar to the organization of cells invading a
      provisional matrix in an in vivo model of wound healing using the chicken
      chorioallantoic membrane. Sprouting cells were defined as myofibroblasts based on
      being alpha-smooth muscle actin-positive but desmin-negative. There was no
      contribution of endothelial cells in outgrowing sprouts. The acquired
      myofibroblastic phenotype was stable since sprout-derived cells resumed sprouting
      in a growth factor-independent manner when re-embedded as spheroids in a fibrin
      matrix. Invasive growth and sprouting of vascular smooth muscle cells was not
      limited to chicken cells since a similar response was seen when spheroids
      composed of purified primary human aortic smooth muscle cells were embedded in
      fibrin. Finally, a technique for flat visualization of the three-dimensional
      sprouting and a quantification method is described. This ex vivo model allows
      quantitative analysis of invasive growth and differentiation of vascular smooth
      muscle cells and fibroblasts into myofibroblasts.

PMID- 15723088
TI  - Cilium-generated signaling and cilia-related disorders.
AB  - Biologists have long known that humans experience their environment through
      cilia. Light, odorant, and sound perception depend on these microtubule-filled,
      complex organelles present on cells in primary sensory tissues. Recently,
      discoveries on the mechanism of assembly of cilia (flagella) in the lowly,
      biflagellated, eucaryotic green alga Chlamydomonas have triggered a renaissance
      of interest in the organelles along with a recognition of their key sensory roles
      in nonsensory tissues. Chlamydomonas researchers uncovered an entirely new set of
      cellular machinery essential for transporting the protein components of cilia and
      flagella in all ciliated/flagellated eukaryotic cells between their site of
      synthesis in the cell body and their site of assembly at the tip of the flagellum
      (intraflagellar transport: IFT). Prompted by the surprising observations that
      disruption of IFT genes in mice led to polycystic kidney disease (PKD) and that
      PKD proteins are present on the sensory cilia of Caenorhabditis elegans,
      researchers have made a direct connection between PKD and cilia. At least five
      (and possibly all) of the seven identified human genes disrupted in PKD and a
      related disorder nephronophthisis encode proteins expressed in the primary cilia
      that project into the lumen from the epithelial cells that line renal tubules.
      Moreover, the renal cilia are flow sensors and at least two of the PKD genes
      encode ciliary transmembrane proteins essential for mechanosensation. Although
      their roles have not yet been as clearly identified, cilia also are at the center
      of a rare human disorder, Bardet-Biedl syndrome (BBS), in which patients exhibit
      phenotypes of common human diseases, including obesity and increased incidence of
      hypertension and diabetes. Five of the eight known BBS genes encode basal body or
      cilia proteins in mice or humans, and homologues of two of the remaining genes
      are present in basal bodies/cilia of model organisms. Here we briefly describe
      the biology of cilia and flagella, we outline how studies on model organisms have
      led to our current understanding of the roles of these organelles and their
      proteins in health and disease, and we highlight the notion that the primary
      cilia present on cells throughout the body, even those on brain neurons, may be
      essential for as yet undiscovered cilium-generated signaling functions.

PMID- 15723090
TI  - Validation of IKK beta as therapeutic target in airway inflammatory disease by
      adenoviral-mediated delivery of dominant-negative IKK beta to pulmonary
      epithelial cells.
AB  - Asthma is an inflammatory disease of the lungs and the transcription factor NF
      kappa B regulates the production of numerous inflammatory mediators that may have
      a role in the pathogenesis of asthma. Hence, the signalling pathways leading to
      NF-kappa B activation are considered prime targets for novel anti-inflammatory
      therapies. The prevention of NF-kappa B activity in mice, through the knockout of
      IKK beta or p65, causes fatal liver degeneration in utero making it difficult to
      determine the full implications of inhibiting NF-kappaB activity in tissues
      physiologically relevant to human diseases. This study used adenovirus delivery
      of a dominant inhibitor of NF-kappaB (I kappa B alpha delta N) and dominant
      negative IKK alpha (IKK alpha(KM)) and IKK beta (IKK beta(KA)) to investigate the
      role of the individual IKKs in NF-kappa B activation and inflammatory gene
      transcription by human pulmonary A549 cells. Overexpression of IKK beta(KA) or I
      kappa B alpha delta N prevented NF-kappa B-dependent transcription and DNA
      binding. IKK beta(KA) also prevented I kappa B alpha kinase activity. Similarly,
      IKK beta(KA) and I kappa B alpha delta N overexpression also inhibited IL-1beta-
      and TNF alpha-dependent increases in ICAM-1, IL-8 and GM-CSF in addition to IL
      1beta-mediated increases in cyclooxygenase-2 expression, whereas IKK alpha(KM)
      overexpression had little effect on these outputs. IKK beta(KA) also reduced cell
      viability and induced caspase-3 and PARP cleavage regardless of the stimuli,
      indicating the induction of apoptosis. This effect seemed to be directly related
      to IKK beta kinase activity since I kappa B alpha delta N only induced PARP
      cleavage in TNF alpha-treated cells. These results demonstrate that inhibition of
      IKK beta and NF-kappa B suppresses inflammatory mediator production and reduces
      A549 cell viability. Thus, novel therapies that target IKK beta could have potent
      anti-inflammatory effects and may be beneficial in the treatment of certain
      cancers.

PMID- 15723089
TI  - Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from
      dimethylnitrosamine-induced liver fibrosis.
AB  - 1 Chronic liver disease is characterized by an exacerbated accumulation of
      matrix, causing progressive fibrosis, which may lead to cirrhosis. Transforming
      growth factor beta (TGF-beta), a well-known profibrotic cytokine, transduces its
      signal through the ALK5 ser/thr kinase receptor, and increases transcription of
      different genes including PAI-1 and collagens. The identification of GW6604 (2
      phenyl-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine), an ALK5 inhibitor, allowed us
      to evaluate the therapeutic potential of inhibiting TGF-beta pathway in different
      models of liver disease. 2 A cellular assay was used to identify GW6604 as a TGF
      beta signaling pathway inhibitor. This ALK5 inhibitor was then tested in a model
      of liver hepatectomy in TGF-beta-overexpressing transgenic mice, in an acute
      model of liver disease and in a chronic model of dimethylnitrosamine (DMN)
      induced liver fibrosis. 3 In vitro, GW6604 inhibited autophosphorylation of ALK5
      with an IC(50) of 140 nM and in a cellular assay inhibited TGF-beta-induced
      transcription of PAI-1 (IC(50): 500 nM). In vivo, GW6604 (40 mg kg(-1) p.o.)
      increased liver regeneration in TGF-beta-overexpressing mice, which had undergone
      partial hepatectomy. In an acute model of liver disease, GW6604 reduced by 80%
      the expression of collagen IA1. In a chronic model of DMN-induced fibrosis where
      DMN was administered for 6 weeks and GW6604 dosed for the last 3 weeks (80 mg kg(
      1) p.o., b.i.d.), mortality was prevented and DMN-induced elevations of mRNA
      encoding for collagen IA1, IA2, III, TIMP-1 and TGF-beta were reduced by 50-75%.
      Inhibition of matrix genes overexpression was accompanied by reduced matrix
      deposition and reduction in liver function deterioration, as assessed by
      bilirubin and liver enzyme levels. 4 Our results suggest that inhibition of ALK5
      could be an attractive new approach to treatment of liver fibrotic diseases by
      both preventing matrix deposition and promoting hepatocyte regeneration.

PMID- 15723091
TI  - The role of joint nerves and mast cells in the alteration of vasoactive
      intestinal peptide (VIP) sensitivity during inflammation progression in rats.
AB  - The present study examined the peripheral effects of vasoactive intestinal
      peptide (VIP) on rat knee joint blood flow during acute and chronic inflammation.
      The involvement of joint nerves and synovial mast cells on these effects was also
      investigated. Prior to blood flow assessment, animals were deeply anaesthetised
      with ethyl carbamate (urethane; 2 mg kg(-1) i.p.). Local application of VIP (10(
      13)-10(-9) mol) onto the capsular surface of normal rat knee joints caused a dose
      dependent increase in synovial perfusion with an ED50 of 1.2 x 10(-11) mol. The
      dilator effect of the peptide was transient with the maximal response occurring
      approximately 1 min after drug administration. VIP-induced vasodilatation was
      blocked by co-administration of the VIP receptor antagonist VIP(6-28) (10(-9)
      mol). The inhibitory effect of the antagonist was consistent across the entire
      VIP dose range (P=0.01). The vasoresponsiveness to VIP was significantly
      attenuated in acutely inflamed joints; however, surgical denervation of acutely
      inflamed knees re-established the vasodilator effect of the neuropeptide. Topical
      application of VIP to 1- and 3-week adjuvant monoarthritic knees produced a
      hyperaemic response, which was not significantly different from normal (P=0.06
      and 0.73 for 1- and 3-week adjuvant treated joints, respectively). Stabilisation
      of synovial mast cells by disodium cromoglycate (cromolyn) pretreatment did not
      alter the vasoresponsiveness to VIP in acute or chronically inflamed joints. The
      vasodilatatory effect of VIP is lost during acute knee joint inflammation and
      this abrogated effect is neurally dependent. In the chronic phase of knee joint
      inflammation, VIP-mediated hyperaemia recovers to normal levels. Synovial mast
      cells do not influence the vasomotor effects of exogenously applied VIP in
      inflamed knee joints.

PMID- 15723092
TI  - Signaling of short- and long-term regulation of intestinal epithelial type 1
      Na+/H+ exchanger by interferon-gamma.
AB  - The present study evaluated the effect of interferon-gamma (IFN-gamma) on
      intestinal Na+/H+ exchange (NHE) activity and the intracellular signaling
      pathways set into motion after IFN-gamma receptor activation. Caco-2 cells
      express endogenous NHE1, NHE2 and NHE3 proteins, as detected by immunoblotting.
      Short- (0.5 h) and long- (24 h) term exposure of Caco-2 cells to IFN-gamma
      resulted in a concentration-dependent decrease in NHE activity. Inhibition of NHE
      activity by IFN-gamma was absent in cariporide-treated cells, but not in cells
      treated with S-3226. The long-term exposure to IFN-gamma was accompanied by a 20%
      increase in surface NHE1 abundance and no changes in total NHE1 abundance.
      Inhibition of Raf1, mitogen-activated protein kinase kinase (MAPKK/MEK) and p38
      MAPK with, respectively, GW 5074, PD 98059 and SB 203580 and downregulation of
      protein kinase C (PKC) with phorbol-12,13-dibutyrate (100 nM for 24 h) prevented
      inhibition of NHE activity by IFN-gamma (0.5 and 24 h exposure). The signal
      transducer and activator transcription factor 1 (STAT1) inhibitor
      epigallocatechin-3-gallate (EGCG) prevented inhibition of NHE activity by long-
      but not the short-term treatment with IFN-gamma. Treatment with IFN-gamma
      activated phospho-p38 MAPK, this effect being detected as early as 1 h,
      persisting over 3 h and decreasing after 24 h. IFN-gamma produced a sustained
      action of phospho-STAT1 that was prevented by EGCG and partially attenuated by SB
      203580 and insensitive to downregulation of PKC. In conclusion, short- and long
      term inhibition of NHE1 activity by IFN-gamma involves a complex signaling
      pathway that includes PKC activation and STAT1 phosphorylation, respectively, but
      is not accompanied by downregulation of NHE1.

PMID- 15723093
TI  - Hyperforin activates nonselective cation channels (NSCCs).
AB  - A large body of evidence supports the preclinical antidepressant profile of
      hyperforin including inhibition of the synaptosomal uptake of several
      neurotransmitters by hyperforin and studies in behavioural models. In contrast to
      other antidepressants, hyperforin does not directly inhibit neurotransmitter
      transporters, but instead uptake inhibition seems to be the consequence of an
      elevated intracellular sodium concentration ([Na+]i). The mechanism of hyperforin
      induced elevation of [Na+]i was investigated using two different cell types:
      human platelets and rat pheochromocytoma cells (PC12 cells). In both cell
      systems, hyperforin increased both [Na+]i and free intracellular Ca2+
      concentration ([Ca2+]i). One pathway for Na+ and Ca2+ entry is mediated by
      nonselective cation channels (NSCCs), which can be blocked by SK&F 96365 and LOE
      908. LOE 908 is a blocker of both NSCC1 and NSCC2 subclasses, while SK&F 96365
      blocks NSCC2 only. Both SK&F 96365 and LOE 908 completely inhibited the
      hyperforin-induced influx of Na+ and Ca2+ into platelets and PC12 cells. This
      indicates that hyperforin is mainly active upon NSCC2. The effect of hyperforin
      is inhibited by La3+ and Gd3+, indicating that there is a potential homology with
      canonical transient receptor potential protein channels (TRPC channels).
      Moreover, La3+ and Gd3+ attenuate the effect of hyperforin on serotonin uptake in
      human platelets. Additionally, hyperforin induces barium influx in PC12 cells and
      this influx can be inhibited by SK&F 96365, LOE 908, Gd3+ and La3+. In summary,
      these findings suggest that hyperforin represents a new principle for preclinical
      antidepressant activity, modulating brain neurotransmission by inhibition of
      neurotransmitter uptake via activation of NSCCs.British Journal of Pharmacology
      (2005) 145, 75-83. doi:10.1038/sj.bjp.0706155.

PMID- 15723095
TI  - ClC-3: more than just a volume-sensitive Cl- channel.
AB  - Pulmonary vascular medial hypertrophy due to enhanced pulmonary artery smooth
      muscle cell (PASMC) proliferation and/or decreased PASMC apoptosis is a primary
      cause of increased pulmonary vascular resistance and arterial pressure in
      patients with pulmonary arterial hypertension. While many factors can contribute
      to this form of vascular remodeling, it is generally agreed upon that altered
      transmembrane ion flux via ion channels is involved. While much focus has
      centered on the role of cations and cation channels in controlling PASMC
      contraction and proliferation, anion efflux via Cl- channels has recently gained
      interest for its role in SMC proliferation, differentiation, migration,
      contraction, and angiogenesis. In this issue, Dai et al. report that the putative
      volume-sensitive ClC-3 channel is upregulated in PASMC from monocrotaline-induced
      pulmonary hypertensive rats and in inflammatory cytokine-treated canine PASMC.
      They also provide evidence that ClC-3 upregulation may protect against oxidative
      stress-induced PASMC necrosis, thereby improving PASMC survival and promoting
      medial hypertrophy.

PMID- 15723094
TI  - Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by
      radioligand binding and quantitative competitive RT-PCR: changes in ageing.
AB  - 1. We investigated muscarinic receptors in the detrusor and mucosa of the human
      bladder body. Radioligand-binding studies with [(3)H]QNB were conducted using
      specimens collected from patients (36-77 years) with normal bladder function,
      undergoing surgery. For RT-PCR, biopsies of normal bladder were obtained from
      patients (30-88 years) undergoing check cystoscopy. 2. Binding of [(3)H]QNB in
      detrusor (n=20) was of high affinity (K(D) 77.1 (55.2-99.0) pM) and capacity
      (B(max) 181+/-7 fmol mg protein(-1)). Similar values were obtained in mucosa
      (n=6) (K(D) 100.5 (41.2-159.9) pM; B(max) 145+/-9 fmol mg protein(-1)). 3.
      Competition-binding experiments in detrusor membranes with muscarinic receptor
      antagonists including trospium, darifenacin, 4-DAMP, methoctramine, AQ-RA 741, AF
      DX 116 and pirenzepine indicated a receptor population of 71% M(2), 22% M(3) and
      7% M(1). In the mucosa, 75% of sites were M(2) receptors, with 25% M(3)/M(5). 4.
      Using RT-PCR, expression of M(1), M(2), M(3) and M(5) mRNA was demonstrated in
      both detrusor and mucosa. 5. The presence of a high density of mainly M(2)
      muscarinic receptors in the mucosa appears to be a novel finding and raises the
      question of their physiological significance and the source of their endogenous
      ligand. 6. There was a negative correlation of receptor number (B(max)) with age
      in detrusor muscle from male patients (P=0.02). Quantitative competitive RT-PCR
      demonstrated a selective age-related decrease in mRNA for muscarinic M(3) but not
      M(2) receptors, in both male (P<0.0001) and female (P=0.019) detrusor. These
      findings correspond with reports of decreased detrusor contractility with ageing.

PMID- 15723096
TI  - ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and
      canine pulmonary artery.
AB  - Cl- channels have been implicated in essential cellular functions including
      volume regulation, progression of cell cycle, cell proliferation and contraction,
      but the physiological functions of the ClC-3 channel are controversial. We tested
      the hypothesis that the ClC-3 gene (ClCn-3) is upregulated in hypertensive
      pulmonary arteries of monocrotaline-treated rats, and upregulated ClC-3 channel
      aids viability of pulmonary artery smooth muscle cells (PASMCs). Experimental
      pulmonary hypertension was induced in rats by a single subcutaneous
      administration of monocrotaline (60 mg kg(-1)). Injected animals developed
      characteristic features of pulmonary hypertension including medial hypertrophy of
      pulmonary arteries and right ventricular hypertrophy. Reverse transcriptase
      polymerase chain reaction (RT-PCR), immunohistochemistry and Western immunoblot
      analysis indicated that histopathological alterations were associated with
      upregulation of the ClC-3 mRNA and protein expression in both smooth muscle cells
      of hypertensive pulmonary arteries and in cardiac myocytes. RT-PCR analysis of
      mRNA, extracted from canine cultured PASMCs, indicated that incubation with the
      inflammatory mediators endothelin-1 (ET-1), platelet-derived growth factor
      (PDGF), interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF alpha),
      but not transforming growth factor beta (TGFbeta), upregulated ClC-3 mRNA.
      Adenovirus-mediated delivery and overexpression of ClC-3 in canine PASMCs
      improved cell viability against increasing concentrations of hydrogen peroxide
      (H2O2, range 50-250 microM). In conclusion, upregulation of ClC-3 in rat
      hypertensive lung and heart is a novel observation. Our functional data suggest
      that upregulation of ClC-3 is an adaptive response of inflamed pulmonary artery,
      which enhances the viability of PASMCs against reactive oxygen species.

PMID- 15723098
TI  - Mefenamic acid as a novel activator of L-type voltage-dependent Ca2+ channels in
      smooth muscle cells from pig proximal urethra.
AB  - The effects of mefenamic acid and Bay K 8644 on voltage-dependent nifedipine
      sensitive inward Ba2+ currents in pig urethral myocytes were investigated by use
      of conventional whole-cell configuration patch clamp. Mefenamic acid increased
      the peak amplitude of voltage-dependent nifedipine-sensitive inward Ba2+ current
      without shifting the position of the current-voltage relationship. Mefenamic acid
      (300 microM) caused little shift in the activation curve although the voltage
      dependence of the steady-state inactivation was shifted to more positive
      potentials by 11 mV in the presence of mefenamic acid. Bay K 8644 (> or = 100 nM)
      enhanced voltage-dependent nifedipine-sensitive inward Ba2+ currents in a
      concentration- and voltage-dependent manner, shifting the maximum of the current
      voltage relationship by 10 mV in the hyperpolarizing direction. Bay K 8644 (1
      microM) significantly shifted the voltage dependence of the activation curve to
      more negative potentials by approximately 9 mV although Bay K 8644 caused little
      shift in the steady-state inactivation curve. These results indicate that
      mefenamic acid increased voltage-dependent nifedipine-sensitive inward Ba2+
      currents through the activation of L-type Ca2+ channels with different kinetics
      from those of Bay K 8644 in pig urethral myocytes.

PMID- 15723097
TI  - Inhibition of granuloma-associated angiogenesis by controlling mast cell mediator
      release: role of mast cell protease-5.
AB  - We investigated the role of mast cells in granuloma-associated angiogenesis in
      rat by using: (i) a mast cell membrane stabilizer, ketotifen; (ii) a mast cell
      depleting agent, compound 48/80. Moreover, we focused on the role of chymases,
      which exhibit proinflammatory and pro-angiogenic properties by using: (i)
      chymostatin, an inhibitor of chymase activity; (ii) a specific antisense
      oligonucleotide (AS-ODN) designed against rat mast cell protease-5 (rMCP-5), the
      most abundantly expressed chymase in the skin. The formation of granuloma was
      evaluated, as wet weight, 96 h after the subcutaneous implant of two lambda
      carrageenin (1%)-soaked sponges on the back of male Wistar rats. Angiogenesis was
      evaluated as haemoglobin content in the granulomatous tissue and as level of
      tumour necrosis factor-alpha (TNF-alpha) in the exudates. A single injection of
      ketotifen (1-5-25 mg kg(-1) i.p.) significantly reduced granuloma formation by
      31.6, 44.6 and 71.9%, and haemoglobin content by 17.0, 35.0 and 66.2%, suggesting
      that the release of mediator(s) from mast cells modulates the process.
      Chymostatin (5-10 nmol(-1) site(-1) day(-1)) reduced granuloma-associated
      angiogenesis by 57.3 and 70.0%. RT-PCR analysis showed that rMCP-5 mRNA amounts
      were significantly reduced by rMCP-5 AS-ODN (1.25-2.5-5.0 nmol site(-1)) by 69.5,
      72.5 and 81.8%. In parallel experiments, rMCP-5 AS-ODN (1.25, 2.5, 5.0 nmol site(
      1)) strongly reduced granuloma weight (26.1, 45.0 and 56.3%) and haemoglobin
      content (22.2, 50.4, 62.03%), suggesting that the observed effect is mediated
      through an antisense mechanism. In conclusion, these data suggest that: (i)
      inhibition of mast cell mediators release may represent a novel strategy to
      modulate angiogenesis; (ii) among the chymase family, rMCP-5 is a key promoter of
      angiogenesis in the rat.

PMID- 15723101
TI  - [The oncology patient in emergencies. Epidemiological data].
AB  - Oncology patients do not form a large proportion within the overall figures of an
      emergency service, but their clinical characteristics mean that attending to them
      is often complex. The elaboration of a complete clinical history, specifying the
      characteristics and stage of the tumoural disease, is a basic weapon for taking
      decisions when an emergency arises. According to the data from our centre,
      oncology patients account for 5% of the total of emergency cases. The most
      frequent type of tumour that we deal with is pulmonary, followed by breast and
      colon. It is often the case that these patients come to the emergency department
      several times in the same month and pain is the most frequent reason for
      consultation, although it is normal for them to mention several causes on each
      occasion. In a high percentage of cases the reason for the consultation is
      related to the disease itself, but on as many as 35% of occasions it is an
      intercurrent pathology. The index of admissions is high (around 50%), especially
      if the patient has come for a reason related to the disease. In global terms,
      they account for 14% of total admissions from emergencies.

PMID- 15723099
TI  - The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via
      sigma1 receptor activation: comparison with the effects of dextromethorphan.
AB  - In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan,
      has neuroprotective effects. Dextromethorphan and dimemorfan are high-affinity
      ligands at sigma1 receptors. Dextromethorphan has moderate affinities for
      phencyclidine sites, while dimemorfan has very low affinities for such sites,
      suggesting that these sites are not essential for the anticonvulsant actions of
      dimemorfan. Kainate (KA) administration (10 mg kg(-1), i.p.) produced robust
      convulsions lasting 4-6 h in rats. Pre-treatment with dimemorfan (12 or 24 mg kg(
      1)) reduced seizures in a dose-dependent manner. Dimemorfan pre-treatment also
      attenuated the KA-induced increases in c-fos/c-jun expression, activator protein
      (AP)-1 DNA-binding activity, and loss of cells in the CA1 and CA3 fields of the
      hippocampus. These effects of dimemorfan were comparable to those of
      dextromethorphan. The anticonvulsant action of dextromethorphan or dimemorfan was
      significantly counteracted by a selective sigma1 receptor antagonist BD 1047,
      suggesting that the anticonvulsant action of dextromethorphan or dimemorfan is,
      at least in part, related to sigma1 receptor-activated modulation of AP-1
      transcription factors. We asked whether dimemorfan produces the behavioral side
      effects seen with dextromethorphan or dextrorphan (a phencyclidine-like
      metabolite of dextromethorphan). Conditioned place preference and circling
      behaviors were significantly increased in mice treated with phencyclidine,
      dextrorphan or dextromethorphan, while mice treated with dimemorfan showed no
      behavioral side effects. Our results suggest that dimemorfan is equipotent to
      dextromethorphan in preventing KA-induced seizures, while it may lack behavioral
      effects, such as psychotomimetic reactions.

PMID- 15723102
TI  - [Principal infections in the oncology patient: practical treatment].
AB  - Infectious complications are one of the most important causes of morbi-mortality
      in oncology patients. Neutropenia is the most important risk factor for
      developing infection in the oncology patient. Although the highest mortalities
      continue to be associated with infections due to enterobacterias and Pseudomonas
      aeruginosa, the frequency of infections due to gram-positives is higher. Deep
      fungic infections, like those produced by resistant or infrequent bacteria
      usually occur in late periods of protracted neutropenias. In recent years
      different studies have shown the efficiency of antibiotic patterns in monotherapy
      in the treatment of the neutropenic patient with fever. Cellular
      immunosuppression is not usually as relevant as neutropenia in oncology patients
      without complications. However, the use of high doses of steroids in some
      patients and above all the use of purine analogues and monoclonal antibodies has
      changed this situation in recent years. With these patients it is recommendable
      to use prophylactic measures directed against Cytomegalovirus, Varicela-zoster
      virus, P.carinii (or jirovecii) and fungic infections. Bacteraemia associated
      with endovascular catheterisation is the principal cause of bacteraemia in these
      patients, above all due to gram-positive micro-organisms. In case of infection,
      it is always advisable to remove the catheter. However, under certain
      circumstances, where the placing of a new catheter might be risky given the
      patient's characteristics and where there are agents of low virulence (e.g.
      coagulase-negative staphylococcus), a conservative treatment can be tried. A
      persistence of fever or bacteraemia following removal of the catheter should lead
      to suspicion of the presence of a deep infection, fundamentally suppurated
      thrombophlebitis or endocarditis. An adequate understanding of the infectious
      complications in these patients and their correct treatment and prevention are
      decisive in reducing the high mortality associated with these clinical
      manifestations.

PMID- 15723103
TI  - [Neutropenia and fever in the patient with cancer].
AB  - Infection in the immunocompromised host is a serious clinical situation due to
      its high morbi-mortality and is one of the most frequent complications in the
      patient with cancer. In patients treated with chemotherapy, the risk of infection
      basically depends on the duration and intensity of the neutropenia. It is
      essential to evaluate, the most probable pathogen involved to initiate, a priori,
      the most suitable treatment, and also to evaluate the general clinical situation
      of the patient, because from the very beginning the treatment is quite
      aggressive. Outpatient care is possible for patients at "low risk" of
      complications. By evaluating the antecedents and clinical history of the patient,
      through physical exploration and from the data of laboratory and radiological
      explorations these points can be acknowledged. The early start of broad spectrum
      antibiotherapy is crucial, and in this chapter we review the most recent
      therapeutical recommendations.

PMID- 15723104
TI  - [Thrombosis and cancer].
AB  - Venous thromboembolic disease is a serious complication in patients with cancer.
      Although its incidence is not well known, the association between thromboembolic
      disease and cancer is frequent and is in itself an emergency. Facing clinical
      manifestations compatible with thromboembolic disease, it is imperative to
      elaborate a complete clinical history in order to know which is the tumour the
      patient is suffering from and if there are associated risk factors (if he is the
      bearer of a central venous catheter, if he is receiving treatment with
      chemotherapy, if his cancer has undergone a surgical intervention). Subsequently,
      if we hold a high suspicion of venous thromboembolic disease, treatment should be
      started without waiting for an immediate diagnostic confirmation. Treatment in
      the oncology patient is similar to that in the non-oncology patient, but greater
      attention should be paid to the complications deriving from the treatment, such
      as haemorrhaging, since this can worsen the prognosis of the patient. Due to
      that, efforts should be directed towards a good antithrombotic prophylaxis.

PMID- 15723105
TI  - [Metabolic emergencies in the oncology patient].
AB  - Amongst the principal metabolic situations that can require emergency attention
      in the oncology patient we find: hypercalcaemia, hyponatraemia, tumoural lysis
      syndrome, lactic acidosis, hyperuricaemia, renal failure, hyperammonaemia,
      hypermpotasaemia, etc. Hypercalcaemia is the most frequent metabolic complication
      in oncology, appearing in 10-30% of these patients. It has two main mechanisms,
      tumoural lysis and humoural hypercalcaemia mediated by PTHrP (a protein related
      to parathormone). The principal factor for its diagnosis is suspicion, since some
      symptoms are non-specific and can be attributed to other causes such as
      somnolence, constipation, etc. Treatment will be based on intensity and is
      started with calciuretic measures with an intense hydration with physiological
      serum and on some occasions with furosemide. Anti-reabsorptive measures include
      calcitonin, bisphosphonates, mithramycin, gallium nitrate and on occasions
      corticoids. Bisphosphonates such as pamidronate and zoledronate seem to be highly
      useful in these cases. Hyponatraemia is classified depending on plasmatic
      osmorality; when this is low we find ourselves facing an authentic hyponatraemia
      that can develop with an extra-cellular volume that is high (cardiac
      insufficiency, cirrhosis, nephrotic syndrome and renal insufficiency), low (renal
      and extra-renal sodium losses) and normal (principally SIADH, related to a high
      elimination of sodium in the urine with high urinary osmolarity in spite of this
      being low in blood). Several types of tumour and different chemotherapy drugs can
      produce this SIADH. Treatment will vary according to the type and intensity, but
      in general this is based on hydric restriction and the replacement of the sodium
      deficit, either through physiological serum or through hypertonic saline serums
      depending on the case, and on occasions furosemide for the elimination of excess
      water.

PMID- 15723106
TI  - [Treatment of pain in the oncology patient].
AB  - Pain is a symptom with a high prevalence in patients with cancer and causes an
      important deterioration in their quality of life. With the measures laid out by
      the WHO in 1986, which divides the different therapeutic options available in
      three ascending steps, pain can be controlled in a high percentage of cases.
      Those patients who are difficult to control with these measures can benefit from
      the application of neuromodulation techniques by experts in the treatment of
      chronic pain. The correct employment of the different medicines (non-steroidal
      anti-inflammatory medicines, opiates and coadjuvants), knowledge of the secondary
      effects, loss of fear in the face of opiates and knowledge of the different algic
      syndromes associated with the oncology patient, must be accompanied by a suitable
      evaluation of the pain according to the different scales, both in the phase of
      the treatment's initiation and in the follow-up of the patient.

PMID- 15723107
TI  - [Acute nutritional problems in the oncology patient].
AB  - Alterations to the nutritional state are frequent in oncology patients. These
      constitute an important medical problem, with a tendency to rise in recent years.
      Some tumours usually appear more frequently in persons with prior malnutrition or
      excessive consumption of alcohol or tobacco. But besides, either because of the
      disease, or because of the treatment to which they are subjected, it is
      frequently the case that oncology patients show problems of deglutition and
      require the placement of probes for enteral nutrition. The present paper offers
      an initial evaluation of the nutritional state of these patients and,
      subsequently, of the most important problems that patients with enteral nutrition
      can present in emergencies.

PMID- 15723108
TI  - [Respiratory emergencies].
AB  - Respiratory emergencies in a patient with cancer can have their origin in
      pathologies of the airway, of the pulmonary parenchyma or the large vessels. The
      cause can be the tumour itself or concomitant complications. Obstruction of the
      airway should be initially evaluated with endoscopic procedures. Surgery is
      rarely possible in serious situations. The endobronchial placement of stents or
      radioactive isotopes (brachytherapy), tumoural ablation by laser or photodynamic
      therapy can quickly alleviate the symptoms and re-establish the air flow.
      Treatment of haemoptysis depends on the cause that is provoking it and on its
      quantity. Bronchoscopy continues to be the front line procedure in the majority
      of cases; it provides diagnostic information and can interrupt bleeding through
      washes with ice-cold serum, endobronchial plugging or topical injections of
      adrenaline or thrombin. External radiotherapy continues to be an extraordinarily
      useful procedure in treating haemoptysis caused by tumours and in carefully
      selected situations of endobronchial therapy with laser or brachytherapy, and
      bronchial arterial embolisation can provide a great palliative effect.
      Respiratory emergencies due to pulmonary parenchyma disease in the oncology
      patient can have a tumoural, iatrogenic or infectious cause. Early recognition of
      each of these will determine the administration of a specific treatment and the
      possibilities of success.

PMID- 15723109
TI  - [Malign obstruction of the superior vena cava].
AB  - The present paper offers a review of the malign syndromes of the superior vena
      cava, their clinical expressions related to the anatomical characteristics of the
      compartment where the superior vena cava runs, the diagnostic requirements for
      realising treatment under the best conditions and the ensemble of measures that
      must be adopted in dealing with this.

PMID- 15723110
TI  - [Acute dysphagia of oncological origin. Therapeutic management].
AB  - Dysphagia is one of the most frequent syndromes in patients with tumours of the
      head and neck, and the oesophagus. This can be the initial symptom or, more
      frequently, related to the oncological treatment. We review the most important
      therapeutic and physio-pathological aspects of acute dysphagia of oncological
      origin. Deglutition is a complex process in which numerous muscular-skeletal
      structures intervene under the neurological control of different cranial nerves.
      The complex neuro-muscular coordination needed for a correct deglutition can be
      affected by numerous situations, both from the effect of the tumours and from
      their treatment, basically surgery or radiotherapy. In conclusion, it can be
      affirmed that for a suitable treatment of oncological dysphagia, a correct
      initial evaluation and an active treatment are required, since not only the
      patient's quality of life but, on numerous occasions, the possibility of
      continuing the treatment and thus maintaining the possibilities of a cure depend
      on control of the dysphagia.

PMID- 15723111
TI  - [Treatment of emesis induced by chemotherapy].
AB  - Respiratory emergencies in a patient with cancer can have their origin in
      pathologies of the airway, of the pulmonary parenchyma or the large vessels. The
      cause can be the tumour itself or concomitant complications. Obstruction of the
      airway should be initially evaluated with endoscopic procedures. Surgery is
      rarely possible in serious situations. The endobronchial placement of stents or
      radioactive isotopes (brachytherapy), tumoural ablation by laser or photodynamic
      therapy can quickly alleviate the symptoms and re-establish the air flow.
      Treatment of haemoptysis depends on the cause that is provoking it and on its
      quantity. Bronchoscopy continues to be the front line procedure in the majority
      of cases; it provides diagnostic information and can interrupt bleeding through
      washes with ice-cold serum, endobronchial plugging or topical injections of
      adrenaline or thrombin. External radiotherapy continues to be an extraordinarily
      useful procedure in treating haemoptysis caused by tumours and in carefully
      selected situations of endobronchial therapy with laser or brachytherapy, and
      bronchial arterial embolisation can provide a great palliative effect.
      Respiratory emergencies due to pulmonary parenchyma disease in the oncology
      patient can have a tumoural, iatrogenic or infectious cause. Early recognition of
      each of these will determine the administration of a specific treatment and the
      possibilities of success.

PMID- 15723112
TI  - [Emergency treatment of urological complications in cancer patients].
AB  - Patients affected by neoplastic diseases frequently come for consultation to the
      emergency services of our hospitals. A large part of these consultations occur
      due to complications of an urological type, whatever the origin of the tumour
      that the patient presents. The pathology can be secondary to the neoplasy or to
      the means used in its treatment, although they are often complications that
      appear independently of the course of the disease. We offer an outline of the
      most frequent causes of emergency consultation due to urological problems in the
      patient affected by neoplastic diseases, whether they are in the urogential
      apparatus or not. We comment especially on the initial study and treatment by the
      emergency doctor or by the oncologist.

PMID- 15723113
TI  - [Metastatic bone disease. Diagnosis and treatment].
AB  - The high incidence of bone metastasis secondary to carcinomas and its serious
      functional repercussion are motives for constant study and advance in the methods
      of evaluation, diagnosis and treatment. Pain is the most frequently shown
      symptom, although at times the start is a pathological fracture. The classic
      tests of detection and evaluation of the spread of the metastatic disease, simple
      radiology and gammagraphy, are today complemented by others such as computerised
      tomography (CT) and magnetic resonance (MR), improving the information on the
      characteristics of the lesion both inside and outside the bone. On the other
      hand, positron emission tomography (PET) is showing a far higher sensitivity than
      gammagraphy and will probably be the test of the future for the early detection
      of metastasis and of silent primary tumours. The possibilities of treatment of
      bone metastasis are based on the use of bone regenerators, radiotherapy and
      surgery. The former two are indicated in lesions already detected in radiography,
      whether symptomatic or not, if there is no foreseeable risk of fracture. Surgery
      is indicated in situations of poor or null response to those treatments, when the
      risk of fracture is high or a pathological fracture has been produced. Before any
      therapeutic planning, a detailed evaluation of the patient must be carried out,
      both at a local level (size, site, extension of the metastasis) and general (type
      of primary tumour, phase of treatment and response, estimated survival).

PMID- 15723114
TI  - [Medullar compression].
AB  - Medullar compression is an oncological and neurological emergency, whose
      diagnosis and early treatment are key factors for avoiding severe and
      irreversible neurological damage. Paralysis, loss of consciousness and alteration
      in control of the sphincters are the final consequence of the process, and
      represent an important source of morbidity of the oncology patient, besides being
      related to a shorter time of survival. The invasion of the vertebral body by
      haematogenous dissemination is the most frequent cause of medullar compression.
      On occasions it can create mechanical vertebral instability which represents a
      real orthopaedic emergency. Pain is the earliest and most frequent symptom. The
      signs and symptoms appear to the degree that the process advances, passing
      through motor weakness, alterations in consciousness until paralysis and
      incontinence of the sphincters are reached, as a result of complete neurological
      damage. Clinical history and physical exploration should lead to suspicion about
      the level at which medullar compression is developing, and the most important
      complementary exploration is MR of the entire spine, which should be requested
      immediately in order to decide on starting treatment. Treatment is individualised
      and must be started early. In general, corticoids in combination with
      radiotherapeutic oncological treatment and/or surgery are the therapeutic weapons
      to employ.

PMID- 15723115
TI  - [Treatment of intracranial hypertension of malign tumour origin].
AB  - Brain tumours are a frequent cause of intracraneal hypertension syndrome,
      clinically manifested by headache, nausea and vomiting, and a decrease in the
      level of consciousness. The keypoint sign of intracraneal hypertension is
      papilloedema. Other manifestations depend on the localization of the tumour,
      appearing as neurological focality and seizures. The causes of intracranial
      hypertension of tumoural origin are the mass effect of the tumour, brain edema,
      the possibility of intratumoural haemorrhage and hydrocephalus caused by
      obstruction in the circulation of cerebrospinal fluid. The treatments employed,
      medical or surgical, act against these causes.

PMID- 15723117
TI  - Specificity of postsynaptic excitations of different sensory modality in neurons
      of edible snail during learning.
AB  - The development of sensitization in edible snails during intracellular injection
      of oligonucleotides specifically inhibiting C/EBP transcription factors results
      in selective suppression of synaptic facilitation in responses of LPl1 neurons
      evoked by chemical stimulation of the head. At the same time, facilitation of the
      responses to tactile stimulation of the head or foot developed as in control
      sensitized animals. The data are interpreted from the viewpoint of P. K. Anokhin
      hypothesis that integrative function of cerebral neurons involved in construction
      of biologic functional systems is based on peculiar pre- and postsynaptic
      chemical processes selectively projected onto the genome of neural cell.

PMID- 15723118
TI  - Evoked potentials as indicator of possible involvement of ventromedial
      hypothalamus and lateral nucleus of the amygdala in the formation of feeding
      behavior.
AB  - Electrical stimulation of the ventromedial hypothalamus in cats leads to the
      appearance of an additional component in the structure of evoked potentials of
      the amygdala lateral nucleus; this component disappears after discontinuation of
      food reinforcement (suppression of the conditioned reflex). It was concluded that
      the lateral nucleus of the amygdala and ventrolateral hypothalamus, the
      structures belonging to the system of defense behavior, can change their
      congenital characteristics depending on the situation, when involved in the
      feeding behavior system.

PMID- 15723116
TI  - Principles of microRNA-target recognition.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression in
      plants and animals. Although their biological importance has become clear, how
      they recognize and regulate target genes remains less well understood. Here, we
      systematically evaluate the minimal requirements for functional miRNA-target
      duplexes in vivo and distinguish classes of target sites with different
      functional properties. Target sites can be grouped into two broad categories. 5'
      dominant sites have sufficient complementarity to the miRNA 5' end to function
      with little or no support from pairing to the miRNA 3' end. Indeed, sites with 3'
      pairing below the random noise level are functional given a strong 5' end. In
      contrast, 3' compensatory sites have insufficient 5' pairing and require strong
      3' pairing for function. We present examples and genome-wide statistical support
      to show that both classes of sites are used in biologically relevant genes. We
      provide evidence that an average miRNA has approximately 100 target sites,
      indicating that miRNAs regulate a large fraction of protein-coding genes and that
      miRNA 3' ends are key determinants of target specificity within miRNA families.

PMID- 15723119
TI  - Water and salt consumption and suppression of Angiotensin-induced thirst in rats
      after carotid glomectomy.
AB  - Carotid glomectomy in rats reduced daily water consumption and increased daily
      consumption of NaCl solution. Sham operation did not modify water and salt
      consumption. Intraperitoneal injection of angiotensin-II did not stimulate
      drinking motivation in the majority of rats subjected to carotid glomectomy.
      Injection of angiotensin-II to sham-operated and intact animals induced active
      consumption of both fluids during one hour. These results attest to the
      involvement of the carotid body in the regulation of consumption of water and
      sodium ions (the main elements of osmotic blood pressure) and the involvement of
      angiotensin-sensitive receptors of carotid body cells in the formation of thirst
      and salt appetite motivation, regulated by the renin-angiotensin system.

PMID- 15723120
TI  - Parameters of cell energy metabolism during stress in laboratory animals and
      energotropic effect of alpha1-adrenoblocker doxazosin.
AB  - Cytochemical activity of succinate dehydrogenase and lactate dehydrogenase in
      blood lymphocytes, activity of hydroperoxides, MDA, and blood plasma antioxidants
      were studied in experimental animals during immobilization stress after
      preliminary injection of doxazosin. Preliminary adrenergic receptor blockade
      prevented changes in cell metabolism characteristic of immobilization stress. The
      role of adrenergic regulation in the realization of energotropic effects during
      immobilization stress was examined.

PMID- 15723121
TI  - Specific features of the erythroid hemopoietic stem in CBA/CaLac mice with
      neuroses demonstrating good and poor learning capacities.
AB  - We studied changes in the erythroid hemopoietic stem in CBA/CaLac mice with
      experimental neuroses demonstrating good and poor learning capacities (conflict
      situation and paradoxical sleep deprivation followed by training in a 3-arm T
      maze). The animals with different learning capacities exhibited pronounced
      hyperplasia of the erythroid hemopoietic stem in response to neurosis. Activation
      of the erythron in good learners was related to acceleration of division and
      maturation of erythroid precursors and enhanced formation of cell complexes
      containing central macrophage. In poor learners hyperplasia of the erythroid
      hemopoietic stem under conditions of conflict situation manifested in activation
      of proliferation and differentiation (against the background of decreased count
      of erythroid and mixed complexes in the bone marrow), while after paradoxical
      sleep deprivation followed by T-maze training this hyperplasia was associated
      with increased formation of additional hemopoietic islets (against the background
      of desynchronization of division and maturation of erythroid precursor cells).

PMID- 15723122
TI  - Regenerative processes in the cornea after erosion and effects of adhelon on
      these processes.
AB  - Adhelon markedly stimulated regeneration of erosive defects in the corneal
      epithelium. Under the effect of adhelon they healed more than 2-fold more rapidly
      after subtotal chemical torpid erosion than after total mechanical erosion of the
      cornea.

PMID- 15723123
TI  - Changes in the blood lipid-transporting system in rats over the first day of
      experimental peritonitis.
AB  - Changes in the lipid spectrum of blood plasma and composition of high-density
      lipoproteins in outbred albino rats were studied during early stages of
      experimental peritonitis. We revealed an increase in lecithin:cholesterol
      acyltransferase activity, activation of lipolytic production of high-density
      lipoproteins from very-low-density lipoproteins, and substitution of arachidonic
      acid in cholesterol esters for dihomo-gamma-linoleic acid 7 h after induction of
      peritonitis. After 24 h the protein composition and functional activity of high
      density lipoproteins was modified and the amount of saturated fatty acids in
      cholesterol esters increased.

PMID- 15723125
TI  - Kinetic parameters of oxidation of individual fatty acids with ozone.
AB  - Using an original automated analyzer of double bonds we determined the rate
      constants for oxidation of saturated and unsaturated mono- and dienoic fatty
      acids (in vivo substrates for beta-oxidation in the mitochondria) by the ozone
      titration method. The rate constant for O(3) oxidation is maximum for oleic
      monoenoic acid, lower for dienoic linoleic, and very low for saturated palmitic
      acid. The rate constant for oxidation of oleic fatty acid, which by one order of
      magnitude surpasses that for oxidation of essential arachidonic acid, indicates
      that oleic acid is a leading in vivo acceptor of active O(2) species. By the rate
      of trapping active oxygen species and in the quantitative aspect, endogenously
      produced oleic acid can be regarded as the main biological antioxidant.

PMID- 15723124
TI  - Antidiuretic hormone-V2-receptor-aquaporin-2 system in rat kidneys during acute
      inflammation.
AB  - Expression of antidiuretic hormone V(2)-receptor, water channel protein aquaporin
      2, and cytokines interleukin-1b and interleukin-6 was studied in the kidneys of
      rats with acute inflammation produced by intraperitoneal injection of
      lipopolysaccharide in a dose of 250 microg/100 g. Reduced expression of aquaporin
      2 and V(2)-receptor led to impairment of concentration capacity in the kidneys
      and decrease in urine osmolarity.

PMID- 15723126
TI  - Atopy parameters in asthmatic children increase with accumulation of null-alleles
      of glutathione-S-transferase M1.
AB  - Atopy parameters (total IgE, skin prick test, and peripheral blood eosinophil
      count) in children with atopic bronchial asthma depend on the number of
      glutathione-S-transferase M1 mutant alleles in the genotype and on family history
      of asthma.

PMID- 15723127
TI  - Effect of synthetic peptide thrombin receptor agonist encapsulated in
      microparticles based on lactic and glycolic acid copolymer on healing of
      experimental skin wounds in mice.
AB  - PAR1 peptide thrombin receptor agonist (PAR1-AP) was encapsulated in
      microcorpuscles based on lactic and glycolic acid copolymer. The desorption
      profile of the preparation was studied in vitro and its wound-healing effects
      were studied on a model of cut skin wound in mice. The study showed that 90% PAR1
      AP was desorbed over 6 h, but the peptide was detected in eluates from the
      microparticle surface after 23 h. The desorbed peptide retained its physiological
      activity and was capable of activating PAR1 receptors on human platelets. The
      study of the dynamics of experimental skin wound healing in mice showed lower
      number of macrophages in the wounds treated with PAR1-AP microparticles compared
      to the control (open wounds and wounds covered with microparticles) and higher
      number of fibroblasts on day 3 of tissue reparation. Hence, PAR1-AP desorbed from
      microparticles shortened the inflammation phase in the wound. On day 7 the best
      healing parameters were also observed in wounds treated with PAR1-AP
      microparticles, which attests to shortening of the proliferation phase and
      acceleration of wound healing.

PMID- 15723128
TI  - Oxidatively modified fibrinogen modulates blood rheological parameters.
AB  - We studied the effect of UV-oxidized fibrinogen with oxidation degrees of 10 and
      20% on rheological parameters of the blood. The effect of fibrinogen with 10%
      oxidation degree was moderate and variable, which attests to its partial
      compensation with the pool of natural antioxidants. The effect of fibrinogen with
      20% oxidation degree was more pronounced. It dramatically decreased deformability
      of erythrocytes, delayed formation of linear aggregates, accelerated formation of
      3D-aggregates, enhanced the total hydrodynamic strength of aggregates, but
      decreased stability of the largest aggregates. It did not increase plasma
      viscosity, but enhanced viscosity of the blood at all shear rates. At both
      degrees of oxidation, suspension stability of the blood decreased, the Caisson
      viscosity did not change, and the difference between the values of Caisson and
      asymptotic viscosities markedly increased. On the whole, oxidative fibrinogen
      produces negative changes in blood rheological parameters, and its effect depends
      on the degree of oxidation.

PMID- 15723129
TI  - Neutron flow exposure as a test for survival of Artemia salina spores.
AB  - Live and heat-inactivated Artemia salina spores (samples with the same mass and
      filling density) were exposed to a flow of thermal neutrons from a (252)Cf
      radioactive source at an equivalent dose power of about 1 microSv/h. Irradiation
      led to a 4-fold acceleration of nauplius development and to modification of the
      element profiles of live spores. The difference between absorption/diffusion of
      thermal neutrons by live and dead spores was revealed.

PMID- 15723130
TI  - Effect of Betula bark extract on spontaneous and induced mutagenesis in mice.
AB  - Study was performed by counting cells with chromosomal aberrations in C57Bl/6
      mice. Bark dry extract was given perorally in doses of 50, 150, 450, and 1500
      mg/kg. Mutagens dioxidine and cyclophosphamide were injected intraperitoneally in
      doses of 200 and 20 mg/kg, respectively. Bark dry extract in doses of 150 and
      1500 mg/kg did not possess cytogenetic activity. Bark dry extract in doses of 50,
      150, and 450 mg/kg significantly decreased the cytogenetic effect of mutagens
      under various regimens of treatment with the preparation (single combined
      administration, 5-day pretreatment, and 5-day combined administration). Our
      results indicate that bark dry extract possesses antimutagenic properties.

PMID- 15723131
TI  - Effect of destruction of gyrus cinguli in rat brain on the development of
      tolerance to the analgesic effect of morphine and physical dependence on
      morphine.
AB  - We studied the effect of bilateral laser destruction of rat anterior cingulate
      gyrus on the analgesic effect of morphine and development of tolerance and
      physical dependence on morphine. Bilateral laser destruction of the anterior
      cingulate gyrus did not modulate pain sensitivity, analgesic effect of morphine,
      and development of morphine tolerance. Destruction of the cingulate gyrus
      alleviated symptoms of the abstinence syndrome in morphine-dependent animals. We
      showed that morphine-induced analgesia and morphine tolerance are not associated
      with activity of the anterior cingulate gyrus. However, this structure plays a
      key role in the development of physical dependence on morphine and abstinence
      syndrome.

PMID- 15723132
TI  - Role of individual structural features of rabbit kidneys in the predisposition to
      gentamicin nephrotoxicity.
AB  - A relationship between congenital features in the structure of rabbit kidneys and
      sensitivity to gentamicin nephrotoxicity was revealed. Gentamicin nephrotoxicity
      is more pronounced in rabbits with lower diameter of nephron convoluted tubules
      and with smaller cells lining their lumen.

PMID- 15723133
TI  - Selection of E. coli strains for stable transformation with recombinant plasmids
      containing full-length genome of clinical HIV-1 isolates.
AB  - Strain chi6007 obtained from the parent E. coli strain chi5097 is a result of
      ptsH5 mutation, which allowed cells to grow without common components of the
      phosphoenolpyruvate-dependent phosphotransferase system. Segregants of strain
      chi6007 retaining the Pol+ gene responsible for inability to grow at 37 degrees
      C, but gaining rifampicin resistance (RifR) were used for cloning of cointegrate
      plasmids. Pre-integration complexes of HIV-1 were co-integrated with the pBR-322
      plasmid and transformed strain chi6018. Sequencing showed that the pPIC91 hybrid
      plasmid contains full-length genome of HIV-1 with shortened 5-terminal LTR and
      full-length copy of pBR322. Elimination of the pPIC91 plasmid from chi6018 cells
      was followed by the appearance of auxotrophic insertion mutants. Sequencing of
      the insert region showed that chromosome DNA of the host cell includes integrated
      genomes of pBR-322 and HIV-1.

PMID- 15723134
TI  - Activity of human lymphocytes in the presence of carbohydrate-containing
      compounds.
AB  - Treatment with chelating agent abolished stimulation of human lymphocyte blast
      transformation observed in the presence of native microbial glycoproteins.
      Heparin passed through a column packed with aluminum hydroxide inhibited
      cytotoxic activity in natural killer cells. We discuss the possibility of
      regulation of cell functions via modulation of the vector of transport and
      exchange of metal cations in cell microenvironment and the role of macromolecular
      compounds containing carbohydrate components in this process.

PMID- 15723135
TI  - Expression of estrogen receptors-alpha and -beta in primary breast neoplasms and
      tumors exposed to neoadjuvant hormonal therapy.
AB  - We studied the content and expression of mRNA for estrogen receptors-alpha and 
      beta in breast tumors before and after 3-month neoadjuvant hormone therapy with
      antiestrogen tamoxifen and/or aromatase inhibitors. Expression of estrogen
      receptors-alpha and -beta was most often detected in ER+PR+ tumors and most
      significantly decreased in these neoplasms after exemestane therapy.
      Immunocytochemical and radioligand assays showed that tamoxifen and anastrozole
      have little effect on the number of estrogen receptors-alpha. The number of
      progesterone receptors in tumors decreased by the end of anastrozole therapy.
      Estrogen receptors-beta were immunocytochemically revealed in 50% primary breast
      tumors. Anastrozole slightly decreased, while tamoxifen increased the incidence
      of these receptors. Interruption of signaling through estrogen receptors and
      suppression of estrogen biosynthesis had different effects on the receptor status
      of neoplasms and distribution of estrogen receptors-alpha and -beta.

PMID- 15723137
TI  - Telomerase activity in cells of 9-day-old spleen colonies formed by bone marrow
      of normal and thymectomized mice.
AB  - Telomerase activity was measured in spleen colonies, in progeny of individual 9
      day-old splenic CFU formed by the bone marrow from normal (physiological aging)
      and thymectomized mice. Cells of spleen colonies expressed telomerase activity.
      No correlation was found between telomerase activity in spleen colony cells and
      age of animals. Thymectomy of bone marrow donors had no effect on telomerase
      activity. Our results suggest that the thymus plays a role in cell aging.

PMID- 15723136
TI  - Metabolism of lymphocytes in mice with Ehrlich ascites carcinoma.
AB  - The pattern of metabolic processes in lymphocytes of mice with Ehrlich ascites
      carcinoma depended on the stage of tumor growth.

PMID- 15723138
TI  - Effect of melatonin and tetrapeptide on gene expression in mouse brain.
AB  - A microchip technique was used to study expression of 16,897 clones from a cDNA
      library in the brain of mice receiving melatonin or tetrapeptide Epithalon (Ala
      Glu-Asp-Gly). Expression of 53 transcripts in mouse brain underwent significant
      changes after treatment with the preparations. Melatonin and Epithalon modified
      expression of 38 and 22 transcripts, respectively. These preparations produced
      similar changes in the expression of 6 transcripts. Expression of 1 transcript
      (Rp119) was inhibited by melatonin, but induced by Epithalon. The target genes
      are physiologically related to the cell cycle, apoptosis, biosynthesis,
      processing, and transport of nucleic acids. Comparative study of gene expression
      in the brain and heart of CBA mice receiving melatonin and Epithalon suggest that
      these preparations have a tissue-specific biological effect.

PMID- 15723139
TI  - Effect of low-intensity laser radiation on peripheral blood eosinophils.
AB  - The study was performed on peripheral blood eosinophils isolated on a Ficoll
      Verografin continuous-density gradient. Low-intensity laser radiation
      (lambda=0.89 mu, 25-30 mW power, 8 min exposure) induced degranulation of
      peripheral blood eosinophils. The effect of low-intensity laser radiation was
      realized via activation of calcium channels.

PMID- 15723140
TI  - Protective characteristics of platelets in tuberculosis.
AB  - We demonstrated specific changes in platelet structure in different types of
      tuberculous process, in particular, shift in the proportion between alpha
      granules, dense granules, different disorders in the mitochondrial and lysosomal
      apparatus, etc. The role of platelets in immune process is studied.
      Redistribution of alpha-granules in platelets finds a new interpretation in light
      of psycho- and neurotropic effects of their contents. Adhesion and aggregation
      processes and granule release from platelets are regulated by the content of
      serotonin and cyclic nucleotides in these cells.

PMID- 15723141
TI  - Pathomorphological peculiarities of coronary artery ectasias and their role in
      the pathogenesis of sudden cardiac death.
AB  - Polypositional postmortem contrast coronarography and pathomorphological analysis
      were used to study 400 cases of atherosclerotic, postinfarction, arrhythmogenic,
      and hypertensive heart. High incidence of sudden cardiac death was established in
      patients with coronary artery ectasia in atherosclerotic heart. In most cases,
      ectasias were observed in the anterior interventricular branch of the left
      coronary artery with dominant localization in the second and forth segments.
      Correlation was found between the maximum incidence of ectasia in the anterior
      interventricular branch of the left coronary artery and their maximal length,
      diameter, and bag-shaped appearance. We determined characteristic alterations in
      cardiac angioarchitectonics reflecting segmentary location of ectasia reflecting
      inadequacy of coronary circulation and myocardial ischemia leading to ventricular
      fibrillation and sudden cardiac death.

PMID- 15723142
TI  - Polyploidy of smooth myocytes in coronary arteries.
AB  - Study of smooth myocytes in coronary arteries of dogs with experimental
      coarctation of the aorta revealed increased DNA content in myocyte nuclei and
      increased percentage of binucleated cells. Polyploidy of vascular myocytes did
      not disappear after correction of the aortal defect.

PMID- 15723143
TI  - Transplantation of cultured human neural stem cells in rabbits with experimental
      laser-induced damage to the retina.
AB  - Cultured neural stem/progenitor cells from human fetal brain were transplanted
      into the retrobulbar and suprachoroid space in rabbits with laser-induced damage
      to the retina. Transplanted cells survived, retained multipotent activity,
      migrated into the zone of injury, and stimulated reparation and regeneration in
      the traumatized retina.

PMID- 15723144
TI  - Sympathoadrenal system under conditions of increased left and right ventricular
      afterload.
AB  - Adrenergic plexuses in the myocardium and adrenal medulla were studied
      histochemically under conditions of increased left or right ventricular
      afterload. Under conditions of high afterload not accompanied by heart failure
      the density of sympathetic myocardial innervation remained unchanged in the
      loaded ventricle, but increased in the intact ventricle. Comparison of the state
      of the sympathoadrenal system under conditions of increased afterload complicated
      or uncomplicated by heart failure revealed common prognostically unfavorable
      changes: sharp decrease in the density of adrenergic nerve plexuses in the
      ventricular myocardium and activation of adrenal chromaffin cells.

PMID- 15723145
TI  - Establishment of a genetically marked insect-derived symbiont in multiple host
      plants.
AB  - Alcaligenes xylosoxidans subsp. denitrificans, originally isolated from the
      cibarial region of the foregut of the glassy-winged sharpshooter (Homalodisca
      coagulata), was transformed using the Himar1 transposition system to express
      EGFP. Seedlings of six potential host plants were inoculated with transformed
      bacteria and 2 weeks later samples were taken 5 cm away and analyzed by
      quantitative real-time PCR using primers designed to amplify the gene insert. The
      largest colony of 3,591,427 cells/2 cm of A. xylosoxidans subsp. denitrificans
      was found in Citrus limon, with almost all plants testing positive in both
      trials. The amount of colonization decreased in the other plants tested in the
      following order: orange (Citrus sinensis "sweet orange") > chrysanthemum
      (Chrysanthemum grandiflora cv. "White Diamond") > periwinkle (Vinca rosea) >
      crepe myrtle (Lagerstroemia indica) > grapevine (Vitis vinifera cv. Chardonnay).
      The bacterium's preference for citrus paralleled the host insect's preference for
      this same plant. Additional tests determined that A. xylosoxidans subsp.
      denitrificans thrives as a nonpathogenic, xylem-associated endophyte.

PMID- 15723146
TI  - Legionella pneumonia and serum procalcitonin.
AB  - Procalcitonin is a specific marker of severe bacterial infections with systemic
      inflammation. Quantitative evaluation of serum procalcitonin was performed in 140
      patients with Legionella pneumonia. Positive values (>0.5 ng/mL) were found in
      57.1% of the subjects. The positive sample rate was higher in early sera (73.9%
      in the first week) and decreased progressively. Mean values and the positive
      sample rate (69.8%) were higher in sera collected in the first 2 weeks of
      disease. Procalcitonin was positive in 86.7% of legionellosis cases confirmed by
      culture and mean positive values were significantly higher (P < 0.001) than those
      of culture-negative subjects. We conclude that procalcitonin can represent a
      useful prognostic marker for severe suspected Legionella pneumonia in the first 2
      weeks of disease.

PMID- 15723147
TI  - [Early diagnosis of colorectal tumors].
AB  - Colorectal cancer (CRC) is one of the most common causes of cancer mortality in
      Western countries. Approximately six percent of the population will develop
      colorectal cancer during life. Individuals older than 50 years or with a family
      history for colorectal tumors as well as patients with an inflammatory bowel
      disease have an increased risk for CRC. A significant reduction of colorectal
      cancer mortality can be achieved by screening of asymptomatic patients and
      removal of premalignant adenomatous polyp precursors. Colonoscopy is recognized
      as the gold standard, but in future virtual colonoscopy might be a reasonable
      addition. Asymptomatic individuals with an average risk for CRC should be
      screened from the age of 50 and then every 10 years if the examination showed no
      pathological findings. When the individual or family history indicate a higher
      risk for a colorectal neoplasia, screening should begin at the age of 40 or 10
      years before the earliest tumor occurrence in the family. Families with
      hereditary CRC require a special surveillance.

PMID- 15723148
TI  - [Early diagnosis of the functional relevance of coronary heart disease].
AB  - In cases of stable or to a large extent symptom-free coronary heart disease (CHD)
      and atypical symptomatology, the indication for diagnostic cardiac
      catheterization is first confirmed by noninvasive diagnostics of ischemia. This
      can be carried out either with ergometric stress tests or imaging procedures in
      combination with ergometric or pharmacological stress. Myocardial scintigraphy
      and stress echocardiography are established techniques and to an increasing
      extent stress magnetic resonance imaging (MRI). In addition to sensitivity in
      providing evidence for ischemia, technical improvements in computed tomography
      (CT) and MRI have opened up new possibilities for visualizing coronary vessels
      and vascular wall morphology. While CT coronary angiography with its high spatial
      resolution is on the threshold of clinical application for selected patients, MRI
      has the potential for furnishing information on wall movement analysis,
      perfusion, coronary flow measurement, and plaque characterization to become the
      future cardiovascular "all-round examination".

PMID- 15723149
TI  - [Effects of the RALE study. Hyperkalemia following spironolactone treatment].

PMID- 15723150
TI  - The contributions of Usher and others to the elimination of tension from groin
      herniorrhaphy.
AB  - Relaxing incisions (Wolfler 1892) were eventually shown (Read and McLeod, 1981)
      to reduce but not eliminate wound tension after sutured herniorrhaphy of the
      groin. Reinforcing prosthetics became widely shunned because of morbidity until
      Usher et al (1958) introduced polyethylene, then polypropylene mesh (1963) for
      preperitoneal tensionless repair of large defects. Excellent long-term results
      were obtained, with his technique, by Collier and Griswold (1967). Patt (1967)
      envisaged its application to primary hernia. Reis (1899) introduced early
      ambulation. However, it was not until Leithauser (1943), Blodgett (1946), and
      others showed immediate rising accelerated wound healing and reduced
      complications that Farquharson (1955) began outpatient hernioplasty (in 1950)
      under local anesthesia (Cushing 1900). Bellis (1964) followed, performing
      tensionless repair in 25%. Rodriguez and Phillips (1967) described office
      herniorrhaphy, 30% undergoing polypropylene mesh coverage without tension.
      Lichtenstein (1970) reported mesh onlay reinforcement for sutured repair of large
      defects, discharge was within 24 hours. Martin et al (1982) began (in 1972) to
      treat all inguinal herniation in adults with polypropylene mesh "to avoid
      recurrences". Newman did likewise, using tension-free placement (Rodriguez et al)
      in the subaponeurotic plane. Encountering resistance to publication ("real
      surgeons don't use mesh") he, in 1980, asked Lichtenstein to publish and
      popularize the technique. Kelly (1898) introduced plug prosthestic repair of
      femoral herniation. Drainer and Reid (1972) used polypropylene mesh from below
      under local anesthesia. Lichtenstein and Shore followed, treating recurrent
      inguinal defects similarly. Gilbert (1989) applied the technique to indirect
      herniae. Usher and others deserve recognition for their contributions to the
      elimination of tension from herniorrhaphy.

PMID- 15723151
TI  - Open Rives-Stoppa ventral hernia repair made simple and successful but not for
      everyone.
AB  - BACKGROUND: The Rives-Stoppa (RS) repair of ventral incisional hernias (VIHR) is
      technically difficult. It involves the retromuscular placement of mesh anterior
      to the posterior fascia and the primary closure of the anterior fascia.
      Recurrence rates are 0-8%. We proposed that the operation could be done with
      equal success by placing the mesh in an intraperitoneal position and primarily
      closing the fascia anterior to the mesh. METHODS: 81 patients who had undergone
      an open RS-VIHR with intraperitoneal mesh were evaluated for hernia recurrence
      and factors associated with recurrence. RESULTS: 55 women and 26 men (mean BMI
      38+/-9) underwent RS-VIHR (mean age 49+/-11 years). Of these patients, 44 (54%)
      had a prior VIHR, 30 (37%) had an incarcerated hernia and 34 (42%) had multiple
      fascial defects. PTFE was used in 83% and Prolene in 12%. Average LOS was 5.8+/
      12 days. All received perioperative intravenous antibiotics and 28% were
      discharged on oral antibiotics. Follow-up averaged 30+/-24 months. Recurrent VIH
      developed in 12/81 (15%), with three occurring after removal of infected mesh and
      one after a laparotomy. Excluding these four, the recurrence rate was 10%. There
      was no correlation between hernia recurrence and age, BMI, hernia size, number of
      prior repairs, or LOS (t-test p>0.05). Hernia recurrence did not correlate with
      gender, prior peritoneal contamination, incarceration, multiple defects,
      adhesions, mesh type, oral antibiotics, cardiac disease, diabetes, tobacco use,
      or seroma (X(2) p>0.05). Those with a wound infection and/or abscess formation
      had a significantly higher recurrent hernia rate (60% vs. 8%, X(2) p<0.001).
      Patients with pulmonary disease had a significantly higher recurrence rate (50%
      vs. 12%, X(2) p=0.01). CONCLUSIONS: RS-VIHR with intraperitoneal mesh is a
      successful and less technically challenging method of repair than prior
      modifications. Aggressive efforts to identify infection and treat early may
      prevent abscess formation and subsequent recurrent hernia. Patients with chronic
      pulmonary disease have an unacceptably high recurrence rate and should not be
      considered as candidates for elective RS-VIHR.

PMID- 15723152
TI  - Inguinal hernia surgery in The Netherlands: a baseline study before the
      introduction of the Dutch Guidelines.
AB  - BACKGROUND: In 2003 the Dutch Guidelines for treatment of inguinal hernia (IH)
      were published. For treatment of IH in adults, the evidence-based guidelines
      recommend the use of a mesh repair technique. In order to be able to evaluate the
      effects of these guidelines, a baseline analysis of inguinal hernia surgery
      before the introduction of these guidelines had to be performed. The second
      analysis will be performed two years (January-March 2005) after the publication
      of the Guidelines. OBJECTIVE: To make an inventory of IH surgery in the
      Netherlands, before the introduction of guidelines for IH treatment, to serve as
      a baseline for future evaluation of the impact of the implementation of these
      guidelines. METHODS: A retrospective descriptive study was performed in 2003
      using patient and operation charts including IH repairs performed in The
      Netherlands over a three-month period (January-March 2001). RESULTS: 97/133 (73%)
      hospitals cooperated with the study, generating data from a total of 4386 IH in
      3979 patients (3284 adults, 695 children). Mesh techniques were used in 2839
      (78%) adult inguinal hernias while 800 (22%) patients were treated with non-mesh
      techniques. 484 (14.7%) adult patients were operated on during the study period
      for a recurrent hernia from previous years. Early recurrence (<1 year) occurred
      in 2.2% of all patients. Wound infection was documented in 0.8% of all IH. The
      mortality rate was 0.1%. 1257 of the 3284 (38.3%) adults, and 566 of the 695
      children (81.4%), were operated on in ambulatory care. CONCLUSIONS: In the
      episode prior to implementation of the Dutch evidence-based Guidelines for
      treatment of inguinal hernia, 2839 (78%) adult patients were treated with mesh
      repair and 484 (13.3%) patients were treated for a recurrent hernia.

PMID- 15723154
TI  - A macroscopic anatomical investigation of atrioventricular bundle locational
      variation relative to the membranous part of the ventricular septum in elderly
      human hearts.
AB  - Although several gross anatomical investigations on the cardiac conducting system
      have been published, most have presented gross anatomical observations after
      histological confirmation. This is because of the difficulty in dissecting the
      conducting system itself. Additionally, the conducting system has hitherto been
      represented schematically and/or histologically, even in recent regional
      anatomical color atlases of the heart. Therefore most researchers and clinicians
      rarely view a conducting system at the macroscopic level. In this study we reveal
      the detailed-gross anatomical architecture and normal variations in the
      conducting system using 105 elderly human hearts. In particular, we focused on
      the location of the atrioventricular bundle relative to the membranous part of
      the interventricular septum because it has commonly been used as a landmark to
      identify the conducting system. Consequently we found locational variations in
      the atrioventricular bundle to be relatively more frequent in 56 cases (53.3%),
      in contrast to 49 (46.7%) ordinary cases in which this bundle ran just along the
      lower border of the membranous part of the interventricular septum. In the former
      cases we also emphasized the clinical significance of the naked atrioventricular
      bundle running on the membranous part of the interventricular septum in 22 cases
      (21.0%). Some types of lower atrioventricular bundle variation would be important
      for cardiac surgery, especially the operation of the interventricular septal
      defect and can be explained from the developmental viewpoint, i.e., the
      atrioventricular bundle has its origin in the mixture of specialized myocardial
      rings.

PMID- 15723153
TI  - Tension-free repair of hiatal hernia during laparoscopic fundoplication: a ten
      year experience.
AB  - BACKGROUND: The breakdown of a hiatal hernia repair can lead to clinical failure.
      The use of prosthetic material at the esophageal hiatus to strengthen the crural
      repair is relatively new and questions remain. This report examines the safety
      and efficacy of a tension-free crural repair with mesh. PATIENTS AND METHODS:
      Since 1993, 135 consecutive patients (19-86) [9 re-do] completed laparoscopic
      tension-free hiatal hernia repair prior to Nissen wrap. Esophageal hiatus was
      patched with a PTFE mesh (first 112 patients) or a PTFE/ePTFE composite (23
      patients) secured across the defect with staples to each crura. 130 patients
      completed a phone questionnaire during 2003/2004 (mean f/u 64 months). RESULTS:
      There have been no short-term nor long-term infections related to the PTFE mesh.
      Symptoms were resolved or improved and resolved with meds in 122/130 (94%). Early
      re-herniation occurred in one patient after vigorous exercise. CONCLUSIONS: Mesh
      repair/patch of the esophageal hiatus can be done without infection, with results
      similar to standard crural repair and consistent with surgical principles of non
      tension.

PMID- 15723155
TI  - Pre- and postconditioning during cardiac surgery.
AB  - In spite of improved myocardial protection, postoperative arrhythmias and cardiac
      failure are still important problems causing morbidity and mortality in cardiac
      surgery. Ischemic preconditioning has been widely investigated experimentally
      with the purpose of identifying new therapeutic agents, but we have not unraveled
      the underlying mechanisms and we are not able yet to exploit them
      pharmacologically in clinical practice. Studies of preconditioning in cardiac
      surgery provide conflicting results, but the majority of studies show that
      ischemic preconditioning is an effective adjunct to myocardial protection in
      cardiac surgery. Interventions aimed at modifying reperfusion, or
      postconditioning, have the advantage that they also can be used after the
      ischemic insult has occurred, i.e. also in situations with "non-scheduled"
      ischemia. Postconditioning, as preconditioning, needs pharmacological mimics to
      be used routinely in settings of cardiac surgery or other human interventions.
      Possible common signaling pathways of the two phenomena are discussed, and
      suggested directions for clinical studies are outlined.

PMID- 15723156
TI  - Results of the section of the filum terminale in 20 patients with syringomyelia,
      scoliosis and Chiari malformation.
AB  - BACKGROUND: Spinal cord traction caused by a tight filum terminale may be
      considered a pathogenic mechanism involved in the development of syringomyelia,
      the Chiari malformation (type I) and scoliosis. Section of the filum terminale is
      proposed as a useful surgical approach in these conditions. METHODS: Between
      April 1993 and July 2003, a total of 20 patients (8 men and 12 women) with a mean
      age of 33.5 years underwent section of the filum terminale with or without
      opening of the dural sac through a standard sacrectomy. Eight patients suffered
      from scoliosis, 5 from syringomyelia, 2 from Chiari malformation and 5 with a
      combination of these conditions. FINDING: After section of the filum terminale,
      patients with syringomyelia showed an early clinical improvement of dysaesthesia,
      thermo-anaesthesia, hypo-aesthesia and walking difficulties. Rising of the
      medullary conus was also observed. In patients with scoliosis, back pain improved
      dramatically and a curve reduction was noticed, although progression of the curve
      was observed in one case. In patients with Chiari malformation, headache,
      dysaesthesia and paraparesis disappeared. CONCLUSIONS: Section of the filum
      terminale is a useful strategy in the treatment of scoliosis, syringomyelia and
      the Chiari malformation, and offers a new aetiological basis for the
      understanding of these three disorders.

PMID- 15723157
TI  - Micropet imaging: in vivo biochemistry in small animals.
AB  - Significant technological advancements required for imaging physiological
      function in small animals have been achieved in the last few years. Dedicated
      small animals PET scanners are now achieving resolutions that approach the one
      obtainable by autoradiographic methods, while still maintaining enough detection
      sensitivity to reliably measure biologically relevant parameters such as binding
      potentials or rate constants. Such developments have enabled researchers to
      explore in-vivo rodent models of human disease. The future in imaging now lies in
      the development of multi-modality imaging approaches, while the big challenge in
      the next few years will be for the chemists to develop tracers that are more
      specific and reflective of the functional condition under investigation, while
      miniaturizing the chemical synthesis related instrumentation.

PMID- 15723158
TI  - Aspects of ageing in chronic cerebral oligaemia. Mechanisms of degeneration and
      compensation in rat models.
AB  - Increasing life expectancy has raised health problems with respect to 'normal'
      ageing and particularly to age-related disorders. Cerebral oligaemia may become a
      stress factor during ageing, leading to functional and structural deterioration
      in the brain. Therefore, the use of adequate reproducible animal models is
      crucial to study the age-related changes in global cerebral oligaemia as a risk
      factor for cognitive disturbances. Chronic animal models with 2- or 4-vessel
      occlusions may have clinical relevance for patients with a high risk of cerebral
      vessel stenosis or occlusion, e.g. for patients with uni- or bilateral stenosis
      of the carotid arteries or for patients with dementia. Because cerebral oligaemia
      may be an additional stress factor during "normal" ageing we conducted studies in
      young, adult and senescent animals with respect to functional and structural
      changes in the brain. Using rat models of permanent cerebral vessel occlusions,
      long-lasting cerebral oligaemia led to: i) disturbed cerebral energy state, ii)
      discrete changes in neuropathology, iii) moderate cerebral blood flow reduction
      and iv) marked deterioration in animal behavior. In addition, these findings
      suggest that many neuronal properties are preserved as compared to acute
      oligaemia as a result of adaptive mechanisms and that a series of interdependent
      factors regulate brain ageing. The challenge to understand the effects of ageing
      represents a "new frontier" in research, both to prevent degenerative diseases
      and to reduce their consequences. New aspects of the role of rat models of
      permanent cerebral oligaemia are considered. These numerous multifactorial
      approaches are essential to understand the process of ageing and age-related
      brain disorders. The more we learn about it, the more we realize how to achieve
      "successful" and "adaptative" ageing. In this contribution we have discussed some
      of those mechanisms of adaptation and compensation during ageing and subsequent
      to chronic stress conditions (cerebral oligaemia) related to the vascular system.
      In the future, these findings could lead to new neuroprotective strategies for
      counteracting degenerative changes in ageing and in age-associated chronic brain
      diseases.

PMID- 15723159
TI  - Alzheimer's associated inflammation, potential drug targets and future therapies.
AB  - Alzheimer's disease is the most common cause of dementia in the elderly
      population. The most widely used treatment for Alzheimer's disease at present is
      acetylcholinesterase inhibitors, which aim to prolong cognitive function through
      increased synaptic activity, without providing neuroprotection. This treatment is
      only symptomatic and provides modest outcomes for patients. The recent
      elucidation of the inflammatory pathways involved in Alzheimer's disease however,
      has opened doors for better treatment and prevention by identification of areas
      of therapeutic intervention that target the cause of the disease rather than the
      symptoms. This review describes the inflammatory pathways that are thought to be
      present in Alzheimer's disease and some of the new therapies that have shown
      promise, via alteration or inhibition of these pathways. Some of the therapies
      included in this review, which have already demonstrated beneficial effects in
      the treatment of Alzheimer's disease, or have the potential to do so, are
      nonsteroidal anti-inflammatory drugs, statins, RAGE antagonists and antioxidants.

PMID- 15723160
TI  - DNase II polymorphisms associated with risk of renal disorder among systemic
      lupus erythematosus patients.
AB  - DNase II is an important enzyme for DNA fragmentation and degradation during
      programmed cell death and, consequently, a potential candidate gene for genetic
      study of systemic lupus erythematosus (SLE). Genetic associations of DNase II
      with SLE and related phenotypes were examined in Korean patients with SLE. A
      total of 350 Korean SLE patients and 330 healthy subjects were enrolled. Direct
      DNA sequencing and TaqMan were employed. Logistic regression analyses were
      performed to examine the genetic association with SLE and related phenotypes.
      Through direct sequencing in 24 Korean individuals, six sequence variants were
      identified: one in the 5' flanking region, four in exons (including one
      nonsynonymous), and one in the 3' flanking region. Four of these polymorphisms
      were selected for a larger-scale genotyping (350 SLE patients and 330 normal
      controls). No significant associations with the risk of SLE were detected.
      However, further analyses of association with the risk of renal disorder among
      SLE patients revealed several positive associations. One promoter SNP (-1066G>C),
      +2630T>C (Ser145Ser), +6235G>C and one haplotype showed weak associations with
      the risk of nephritis among SLE patients.

PMID- 15723162
TI  - The role of hypothalamic-pituitary-gonadal hormones in the normal structure and
      functioning of the brain.
AB  - Receptors for hormones of the hypothalamic-pituitary-gonadal (HPG) axis that
      regulate reproductive function are expressed throughout the brain, and in
      particular the limbic system. The most studied of these hormones, the sex
      steroids, contain receptors throughout the brain, and numerous estrogenic,
      progestrogenic and androgenic effects have been reported in the brain related to
      development, maintenance and cognitive functions. Although less studied,
      receptors for gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and
      activins also are found throughout the limbic system on a number of cell types,
      and they too transduce signals from circulating hormones as demonstrated by their
      multiple effects on the growth, development, maintenance and function of the
      brain. This review highlights the point that because of the feedback loops within
      the HPG axis, it is difficult to ascribe structural and functional changes during
      development, adulthood and senescence to a single HPG hormone, since a change in
      the concentration of any hormone in the axis will modulate hormone concentrations
      and/or receptor expression patterns for all other members of the axis. The most
      studied of these situations is the change in serum and neuronal concentrations of
      HPG hormones associated with menopause/andropause. Dysregulation of the HPG axis
      at this time results in increases in the concentrations of serum GnRH,
      gonadotropins and activins, decreases in the serum concentrations of sex steroid
      and inhibin, and increases in GnRH and LH receptor expression. Such changes would
      result in significantly altered neuronal signaling, with the final result being
      that there is i.e. increased neuronal GnRH, LH and activin signaling, but
      decreased sex steroid signaling. Therefore, loss of cognitive function during
      senescence, typically ascribed to sex steroids, may also result from increased
      signaling via GnRH, LH or activin receptors. Future studies will be required to
      differentiate which hormones of the HPG axis regulate/maintain cognitive
      function. This introductory review highlights the importance of the
      identification of HPG hormone neuronal receptors and the potential of serum HPG
      hormones to transduce signals to regulate brain structure and function during
      development and adult life.

PMID- 15723161
TI  - Alzheimer's disease: the impact of age-related changes in reproductive hormones.

PMID- 15723164
TI  - Androgens, andropause and neurodegeneration: exploring the link between
      steroidogenesis, androgens and Alzheimer's disease.
AB  - The relationship between menopause and cognitive decline has been the subject of
      intense research since a number of studies have shown that hormone replacement
      therapy could reduce the risk of developing Alzheimer's disease in women. In
      contrast, research into andropause has only recently begun. Furthermore, evidence
      now suggests that steroidogenesis is not restricted to the gonads and adrenals,
      and that the brain is capable of producing its own steroid hormones, including
      testosterone and estrogen. Sex hormones have been demonstrated to be of critical
      importance in the embryonic development of the central nervous system (CNS);
      however, we are only just beginning to understand the role that these hormones
      may play in the normal functioning and repair of the adult mammalian CNS. This
      review will summarize current research into the role of androgens and andropause
      on cognition and the possible mechanisms of action of androgens, with particular
      reference to Alzheimer's disease.

PMID- 15723163
TI  - Estrogens, progestins, menopause and neurodegeneration: basic and clinical
      studies.
AB  - Two classes of ovarian steroids, estrogens and progestins, are potent in
      protecting neurons against acute toxic events as well as chronic
      neurodegeneration. Herein we review the evidence for neuroprotection by both
      classes of steroids, provide plausible mechanisms for these potent
      neuroprotective activities and indicate the need for further clinical trials of
      both estrogens and progestins in protection against acute and chronic conditions
      that cause neuronal death. Estrogens at concentrations ranging from physiological
      to pharmacological are neuroprotective in a variety of in vitro and in vivo
      models of cerebral ischemia and brain trauma as well as in reducing key
      neuropathologies of Alzheimer's disease. While the mechanisms of this potent
      neuroprotection are currently unresolved, a mitochondrial mechanism is involved.
      Progestins have been recently shown to activate many of the signaling pathways
      used by estrogens to neuroprotect, and progestins have been shown to protect
      against neuronal loss in vitro and in vivo in a variety of models of acute
      insult. Collectively, results of these animal and tissue culture models suggest
      that the loss of both estrogens and progestins at the menopause makes the brain
      more vulnerable to acute insults and chronic neurodegenerative diseases. Further
      clinical assessment of appropriate regimens of estrogens, progestins and their
      combination are supported by these data.

PMID- 15723165
TI  - Evidence for the role of gonadotropin hormones in the development of Alzheimer
      disease.
AB  - Differences in the prevalence and age of onset of Alzheimer disease (AD) in men
      and women, and observations that hormone replacement therapy (HRT) may prevent
      the development of AD, caused many to hypothesize that estrogen deficiency
      contributes to AD. However, recent trials using estrogen failed to show any
      benefit in preventing or alleviating the disease. To address this and other
      inconsistencies in the estrogen hypothesis, we suspect that another hormone of
      the hypothalamic-pituitary-gonadal axis, luteinizing hormone (LH), as a major
      factor in AD pathogenesis. Individuals with AD have elevated levels of LH when
      compared with controls, and both LH and its receptor are present in increased
      quantities in brain regions susceptible to degeneration in AD. LH is also known
      to be mitogenic, and could therefore initiate the cell cycle abnormalities known
      to be present in AD-affected neurons. In cell culture, LH increases amyloidogenic
      processing of amyloid-beta protein precursor, and in animal models of AD,
      pharmacologic suppression of LH and FSH reduces plaque formation. Given the
      evidence supporting a pathogenic role for LH in AD, a trial of leuprolide
      acetate, which suppresses LH release, has been initiated in patients.

PMID- 15723166
TI  - Neuroprotective effects of female sex steroids in humans: current controversies
      and future directions.
AB  - Recent findings from the Women's Health Initiative (WHI) have raised considerable
      concern over prolonged use of opposed and unopposed oral conjugated equine
      estrogen (CEE), given the increased risk of serious adverse effects, including
      stroke and venous thromboembolic complications. Furthermore, results from the WHI
      Memory Study (WHIMS) indicated that over 5 years of therapy with Prempro impaired
      performance on global cognitive tests and nearly doubled the risk of dementia.
      These surprising findings were contradictory to cumulative evidence from basic
      science, epidemiological and some intervention studies suggesting hormone therapy
      was cardioprotective and could potentially reduce the risk of dementia. This
      review paper focuses on the neurobiology of estrogen, summarizing the clinical
      evidence for neuroprotective and cognition-enhancing efficacy of estrogen.
      Further, the paper briefly discusses variables that may account for the
      unexpected findings of WHIMS, and offers suggestions for future research.

PMID- 15723167
TI  - Novel therapeutic strategies for Alzheimer's disease based on the forgotten
      reproductive hormones.
AB  - The relationship between hormones and Alzheimer's disease (AD) has been intensely
      researched. While the majority of this work has focused on the sex steroids,
      estrogens, and more recently androgens, a serendipitous patient encounter led one
      of us (R.L.B.) to question whether other hormones of the hypothalamic-pituitary
      gonadal axis might play a role in the pathogenesis of AD. The age-related decline
      in reproductive function results in a dramatic decrease in serum estrogen and
      testosterone concentrations and an equally dramatic compensatory increase in
      serum gonadotropin concentrations. Indeed, there is growing evidence that the
      gonadotropin luteinizing hormone, which regulates serum estrogen and testosterone
      concentrations, is an important causative factor in the development of AD. This
      review provides information supporting the 'gonadotropin hypothesis'. We put
      forth a novel mechanism of how changes in serum luteinizing hormone
      concentrations could contribute to the pathogenesis of AD and discusses potential
      therapeutic anti-gonadotropin compounds.

PMID- 15723168
TI  - The role of insulin and IGF-1 signaling in longevity.
AB  - There are many theories of aging and parameters that influence lifespan,
      including genetic instability, telomerase activity and oxidative stress. The role
      of caloric restriction, metabolism and insulin and insulin-like growth factor-1
      signaling in the process of aging is especially well conserved throughout
      evolution. These latter factors interact with each other, the former factors and
      histone deacetylases of the SIR family in a complex interaction to influence
      lifespan.

PMID- 15723169
TI  - Gene expression in spermiogenesis.
AB  - Germ cells convey parental genes to the next generation, and only germ cells
      perform meiosis, which is a mechanism that preserves the parental genes. The
      fusion of the products of germ cell meiosis, the haploid sperm and egg, creates
      the next generation. Sperm are the haploid germ cells that contribute genes to
      the egg. In preparation for this, the haploid round spermatids produced by
      meiosis undergo drastic morphological changes to become sperm. During this
      process of spermiogenesis, the nuclear form of the haploid germ cell takes shape,
      the mitochondria are rearranged in a specific manner, the flagellum develops and
      the acrosome forms. Spermatogenesis is supported by precise and orderly
      regulation of gene expression during the changes in chromatin structure, when
      protamine replaces histone. In this report, we summarize the molecular mechanisms
      involved in spermiogenesis.

PMID- 15723170
TI  - The N-terminus of HIV-1 Tat protein is essential for Tat-TAR RNA interaction.
AB  - The human HIV transactivator protein Tat is essential for efficient viral
      transcription that occurs by a complex mechanism involving interaction of Tat
      with the TAR RNA element. This interaction appears to require the mediation of a
      cellular protein, cyclin T1. However, the possibility that Tat and TAR associate
      in a binary Tat-TAR complex has been little investigated. Using a chemically
      synthesized active Tat protein, the kinetic and equilibrium parameters of its
      interaction with TAR were determined by surface plasmon resonance technology.
      Independently of partner and method of immobilization onto the sensor chip, the
      association (k(a) = 5-9 x 10(5) M(-1) s(-1)) and dissociation rate constants
      (k(d) = 1.7-4.3 x 10(-3) s(-1)) yielded similar equilibrium dissociation
      constants (K(d) = 2-8 nM). A truncated peptide encompassing residues 30-86 of Tat
      did not bind to TAR at all. We conclude that Tat can form a high-affinity complex
      with TAR in the absence of cyclin T1 and that the N-terminal domain of Tat is
      essential for this interaction, suggesting a conformational link between this
      domain and the basic domain of Tat. These results are important in our quest for
      developing therapeutic compounds that impair viral replication.

PMID- 15723171
TI  - Interference with MCP-1 gene expression by vector generated triple helix-forming
      RNA oligonucleotides.
AB  - Triple helix-forming oligonucleotides (TFOs) that specifically bind to double
      stranded DNA sequences can be rationally designed, while intracellular delivery
      of single stranded RNA TFOs has not yet been studied in detail. In this report,
      we demonstrate gene and sequence-specific inhibition of MCP-1 gene expression due
      to interference of intracellular-generated single-stranded RNA (CU-TFO) with an
      overlapping SP-1/AP-1 target. Binding of synthetic 19-nucleotide (19-nt) CU-TFO
      to the MCP-1 promoter duplex was verified by triplex blotting. Furthermore, we
      confirmed binding of a 1.1-kb fusion transcript containing the 19-nt pyrimidine
      CU sequence to a plasmid-encoded MCP-1 promoter target duplex at pH 7.0. In
      tumour necrosis factor-alpha-stimulated HEK cells, CU-TFOs inhibited MCP-1
      protein release by 76 +/- 10.2% compared to intracellular-generated control
      oligonucleotides. Interleukin-8 as a control target gene was not affected by CU
      TFO, confirming both highly specific and effective chemokine gene repression by
      transfectable TFO-shuttle vectors.

PMID- 15723172
TI  - New antimicrobial activity for the catecholamine release-inhibitory peptide from
      chromogranin A.
AB  - Catestatin (bCGA(344-364)), an endogenous peptide of bovine chromogranin A, was
      initially characterized for its effect on the inhibition of catecholamine release
      from chromaffin cells. Catestatin and its active domain (bCGA(344-358)) were
      identified in chromaffin cells and in secretion medium. The present study
      identified a potent antimicrobial activity of bCGA(344-358) in the lowmicromolar
      range against bacteria, fungi and yeasts, without showing any haemolytic
      activity. Confocal laser microscopy demonstrated penetration of the rhodaminated
      peptide into the cell membranes of fungi and yeasts and its intracellular
      accumulation. Time-lapse videomicroscopy showed arrest of fungal growth upon
      penetration of the labelled peptide into a fungal filament. We identified several
      catestatin-containing fragments in the stimulated secretion medium of human
      polymorphonuclear neutrophils, suggesting the N-terminal sequence of catestatin
      (bCGA(344-358)) (named cateslytin) as a novel component of innate immunity.

PMID- 15723173
TI  - Confocal microscopy and biochemical analysis reveal spatial and functional
      separation between anandamide uptake and hydrolysis in human keratinocytes.
AB  - The signaling activity of anandamide (AEA) is terminated by its uptake across the
      cellular membrane and subsequent intracellular hydrolysis by the fatty acid amide
      hydrolase (FAAH). To date, the existence of an AEA membrane transporter (AMT)
      independent of FAAH activity remains questionable, although it has been recently
      corroborated by pharmacological and genetic data. We performed confocal
      microscopy and biochemical analysis in human HaCaT keratinocytes, in order to
      study the cellular distribution of AMT and FAAH. We found that FAAH is
      intracellularly localized as a punctate staining partially overlapping with the
      endoplasmic reticulum. Consistently, subcellular fractionation and reconstitution
      of vesicles from membranes of different compartments demonstrated that FAAH
      activity was localized mainly in microsomal fractions, whereas AMT activity was
      almost exclusively in plasma membranes. These results provide the first
      morphological and biochemical evidence to support the view that transport and
      hydrolysis are two spatially and functionally distinct processes in AEA
      degradation.

PMID- 15723174
TI  - Proteolytic modification of Leuconostoc mesenteroides B-512F dextransucrase.
AB  - Multiple active lower molecular weight forms from Leuconostoc mesenteroides B512F
      dextransucrase have been reported. It has been suggested that they arise from
      proteolytic processing of a 170 kDa precursor. In this work, the simultaneous
      production of proteases and dextransucrase was studied in order to elucidate the
      dextransucrase proteolytic processing. The effect of the nitrogen source on
      protease and dextransucrase production was studied. Protease activity reaches a
      maximum early in the logarithmic phase of dextransucrase synthesis using the
      basal culture medium but the nitrogen source plays an important effect on growth:
      the highest protease concentration was obtained when ammonium sulfate,
      casaminoacids or tryptone were used. Two active forms of 155 and 129 kDa were
      systematically obtained from dextransucrase precursor by proteolysis. The amino
      termini of these forms were sequenced and the cleavage site deduced. Both forms
      of the enzyme obtained had the same cleavage site in the amino terminal region
      (F209-Y210). From dextransucrase analysis, various putative cleavage sites with
      the same sequence were found in the variable region and in the glucan binding
      domain. Although no structural differences were found in dextrans synthesized
      with both the precursor and the proteolyzed 155 kDa form under the same reaction
      conditions, their rheological behaviour was modified, with dextran of a lower
      viscosity yielded by the smaller form.

PMID- 15723175
TI  - The curdlan-type exopolysaccharide produced by Cellulomonas flavigena KU forms
      part of an extracellular glycocalyx involved in cellulose degradation.
AB  - The genus Cellulomonas is comprised of a group of Gram-positive, soil bacteria
      capable of utilizing cellulose as their sole source of carbon and energy.
      Cellulomonas flavigena KU was originally isolated from leaf litter and
      subsequently shown to produce large quantities of a curdlan-type (beta-1,3
      glucan) exopolysaccharide (EPS) when provided with an excess of glucose or other
      soluble carbon-source. We report here that curdlan EPS is also produced by
      Cellulomonas flavigena KU when growing on microcrystalline cellulose in mineral
      salts-yeast extract media. Microscopic examination of such cultures shows an
      adherent biofilm matrix composed of cells, curdlan EPS, and numerous surface
      structures resembling cellulosome complexes. Those Cellulomonas species that
      produce curdlan EPS are all non-motile and adhere to cellulose as it is broken
      down into soluble sugars. These observations suggest two very different
      approaches towards the complex process of cellulose degradation within the genus
      Cellulomonas.

PMID- 15723176
TI  - Characterization of Rhodococcus wratislaviensis strain J3 that degrades 4
      nitrocatechol and other nitroaromatic compounds.
AB  - The bacterial strain J3 was isolated from soil by selective enrichment on mineral
      medium containing 4-nitrocatechol as the sole carbon and energy source. This
      strain was identified as Rhodococcus wratislaviensis on the basis of morphology,
      biochemical, physiological and chemotaxonomic characterization and complete
      sequencing of the 16S rDNA gene. The isolated bacterium could utilize 4
      nitrocatechol, 3-nitrophenol and 5-nitroguaiacol as sole carbon and energy
      sources. Stoichiometric release of nitrites was measured during degradation of 4
      nitrocatechol both in growing cultures and for stationary phase cells. The J3
      strain was unable to degrade 4-nitroguaiacol, 2-nitrophenol, 4-nitrophenol, 2,4
      dinitrobenzoic acid, 4,5-dimethoxy-2-nitrobenzoic acid and 2,3-difluoro-6
      nitrophenol. The J3 strain is deposited in the Czech Collection of Microorganisms
      as CCM 4930.

PMID- 15723177
TI  - Metschnikowia viticola sp. nov., a new yeast species from grape.
AB  - Two yeast strains, producing needle-shaped ascospores under suitable conditions,
      were isolated from grapes grown in Hungary. Based on these two strains,
      Metschnikowia viticola (type strain NCAIM Y.01705, CBS 9950, JCM 12561) is
      proposed as a new yeast species. Considering its phenotypic features, the
      restriction fragment patterns of 18S rDNA and the sequence of the D1/D2 domain of
      26S rDNA, the proposed new species is closely related to Candida kofuensis.

PMID- 15723178
TI  - Versatile Rhodococcus equi-Escherichia coli shuttle vectors.
AB  - Rhodococcus equi is an intracellular pathogen of macrophages, causing disease in
      young foals, humans, and sporadically other animals. Although R. equi is easy to
      grow and manipulate, the analysis of virulence is hampered by a lack of molecular
      tools. This paper describes the development of a number of versatile plasmids for
      use in R. equi. Plasmids pREV2 and pREV5 use origins of replication derived from
      the Mycobacterium fortuitum plasmids pAL5000 and pMF1. These plasmids and their
      derivatives are compatible in R. equi, allowing their use for analysis of gene
      function in trans. The stability of these plasmids in R. equi in the absence of
      selection for the plasmid borne antibiotic resistance markers, and their
      integrity following passage through Escherichia coli and R. equi was determined.

PMID- 15723179
TI  - Genetic discovery in Xylella fastidiosa through sequence analysis of selected
      randomly amplified polymorphic DNAs.
AB  - Xylella fastidiosa causes many important plant diseases including Pierce's
      disease (PD) in grape and almond leaf scorch disease (ALSD). DNA-based
      methodologies, such as randomly amplified polymorphic DNA (RAPD) analysis, have
      been playing key roles in genetic information collection of the bacterium. This
      study further analyzed the nucleotide sequences of selected RAPDs from X.
      fastidiosa strains in conjunction with the available genome sequence databases
      and unveiled several previously unknown novel genetic traits. These include a
      sequence highly similar to those in the phage family of Podoviridae. Genome
      comparisons among X. fastidiosa strains suggested that the "phage" is currently
      active. Two other RAPDs were also related to horizontal gene transfer: one was
      part of a broadly distributed cryptic plasmid and the other was associated with
      conjugal transfer. One RAPD inferred a genomic rearrangement event among X.
      fastidiosa PD strains and another identified a single nucleotide polymorphism of
      evolutionary value.

PMID- 15723180
TI  - Solid serous cystadenoma of the pancreas: MR imaging with pathologic correlation.
AB  - We report a case of solid type serous cystadenoma of the pancreas. Computed
      tomographic and magnetic resonance (MR) images showed a hypervascular solid tumor
      that was difficult to differentiate from endocrine tumor of the pancreas.
      However, the tumor showed marked hyperintensity similar to that of hepatic cyst
      on MR cholangiopancreatography, indicating not a solid but rather a cystic
      nature. MR cholangiopancreatography (heavily T2-weighted image) is quite useful
      for clearly differentiating solid from cystic tumors.

PMID- 15723190
TI  - Proctitis complicating stapled hemorrhoidectomy: report of a case.

PMID- 15723191
TI  - Minimally invasive femoral nail extraction.
AB  - INTRODUCTION: Case report about a minimally invasive technique for removal of a
      femoral antegrade nail (FAN). Femoral nails are introduced by minimally invasive
      techniques, but are often removed with more invasive surgery. MATERIALS AND
      METHODS: Four cases of young patients are described in whom the femoral nail was
      removed after consolidation by a minimally invasive extraction technique at the
      trochanteric site. By using a threaded wire for locating the proximal entrance of
      the femoral nail followed by reaming over the wire, the entrance of the nail in
      the trochanteric region is freed. Then the extraction bolt can be placed over the
      wire and the nail can be extracted through the same incision as it was inserted
      in, without enlarging the incision. DISCUSSION: This case report discusses a
      technique for minimally invasive femoral nail extraction, not the necessity of
      removing nails. Leaving out the endcap at the initial operation is the only
      preoperative condition, since the endcap blocks the entrance of the nail. This
      operation is done with fluoroscopic guidance. The difficult part is the reaming.
      The reamer must not be damaged when approaching the nail entrance. This minimally
      invasive femoral nail extraction technique is applicable for various types of
      femoral nails. CONCLUSION: Minimally invasive extraction of femoral nails is
      possible and needs more attention. The level of evidence is a level IV case
      series.

PMID- 15723192
TI  - Reconstruction of defects following bone tumor resections by distraction
      osteogenesis.
AB  - INTRODUCTION: The authors present the results of nine patients (two females,
      seven males) who had bone tumors that were treated with en bloc resection and
      distraction osteogenesis between 1991-2000. MATERIALS AND METHODS: The average
      age of the patients was 19.3 years (14-42 years). The histological diagnosis was
      osteosarcoma in four cases, Ewing's sarcoma in two, giant cell tumor in one,
      osteofibrous dysplasia in one and osteoblastoma in one. A uniplanar external
      fixator was applied to one case and circular external fixator to the other eight
      cases. RESULTS: The average follow-up period was 59.1 months (27-129 months). The
      external fixator was removed at an average of 18.1 months (range, 4-19 months).
      The average bone defect after resection was 14 cm (8-24 cm) and the average
      external fixation index, distraction index, and maturation index were 31.5 (18.7
      40.0), 11.2 (10.9-11.2) and 17.8 (7.5-32.7), respectively. The function of the
      affected leg was excellent in four patients, good in three, fair in one and poor
      in one according to the Enneking scoring system. We did not observe any early
      consolidation or osseous binding in the defect area in any patient. Frequent
      complications were pin tract infection and non-union at the docking site.
      CONCLUSION: Our results indicate that the Ilizarov method allows effective
      restoration of bone defects in the treatment of bone tumors despite various
      disadvantages.

PMID- 15723193
TI  - Challenging question: which bone-sparing prosthesis should be used in a young
      patient with avascular necrosis of the hip?

PMID- 15723194
TI  - Bilateral osteonecrosis of the femoral head after pregnancy.
AB  - Published cases of non-traumatic avascular necrosis of the femoral head
      associated with pregnancy are rare. We report a case of a 41-year-old woman who
      suddenly complained of bilateral hip pain 3 weeks after delivery by Caesarean
      section. For a problem of sterility, she had been treated with human menopausal
      gonadotropin and human chorionic gonadotropin (hMG-hCG). Initial radiographs of
      both hip joints were considered regular. After 4 years' evolution, radiographs of
      the hip joint showed collapse of both femoral heads. Bilaterally, osteonecrosis
      of the femoral heads was confirmed by MRI. MRI revealed a band pattern of low
      signal intensity for both hips on T1- and T2-weighted images. She had no history
      of steroid therapy or alcohol abuse. Osteonecrosis was related to pretentaine. A
      bilateral total hip arthroplasty was performed. The literature about avascular
      necrosis of the femoral head associated with pregnancy in previous cases is
      reviewed.

PMID- 15723195
TI  - Suppressors of cytokine signaling in health and disease.
AB  - Cytokines consist of a large family of secreted proteins, including pro
      inflammatory agents, growth hormone and erythropoietin, that utilize the Janus
      kinase (JAK) signal transducer and activator of transcription (STAT) signal
      transduction pathway to mediate many of their key physiologic and pathologic
      actions. These actions include cytokine-mediated inflammation, immunoregulation,
      hematopoiesis and growth. The JAK-STAT pathway is regulated by several processes,
      among which negative feedback regulation by the suppressors of cytokine signaling
      (SOCS), members of a family of eight proteins, is particularly important. Each
      cytokine induces one or more specific SOCS proteins that in turn down-regulate
      the signal initiated by the cytokine. Through their impact on the cytokine
      activated JAK-STAT pathway, the SOCS proteins are involved in many diseases that
      come to the attention of the pediatric nephrologist. For example, an increase in
      the expression of SOCS-2 and -3 may be a cause of growth hormone resistance and
      thus may contribute to the growth retardation that affects children with chronic
      renal failure. Because of their obvious biologic importance, the SOCS proteins
      have been the subject of intense research that includes the development of
      strategies to utilize these proteins to control cytokine-induced JAK/STAT signal
      transduction for therapeutic purposes.

PMID- 15723196
TI  - A diagnostic approach for the child with hypertension.
AB  - Hypertension during childhood is not rare, with an estimated prevalence of
      between 1% and 2%, although it is often an underrecognized clinical entity.
      Elevated blood pressure may be a sign of underlying disease or it may represent
      early onset of essential hypertension. In recent years the measurement of blood
      pressure has been emphasized as an important component of the routine pediatric
      physical examination that enables early detection of children with hypertension.
      In the evaluation of the child with documented blood pressure elevation,
      confirmation of truly and persistently elevated blood pressure is of the utmost
      importance. In addition, a thorough history and a full clinical examination are
      essential. These are followed by appropriate investigations, which are tailored
      to the age of the child and to the severity of the blood pressure elevation.
      Investigations should not only focus on a search for the underlying cause, but
      also on establishing effects on target organs, complications or additional
      diseases and on assessment of the total cardiovascular risk to the individual
      patient. An algorithm, which is a valuable diagnostic tool for the diagnosis and
      management of the child with hypertension, is presented. All children with
      confirmed hypertension need long-term follow-up, counseling and treatment. In
      those cases where an underlying cause of the hypertension is detected, the
      established diagnosis then determines the specific therapy and management.

PMID- 15723198
TI  - A review of the action of tacrolimus (FK506) on experimental models of rheumatoid
      arthritis.
AB  - Tacrolimus (FK506) is an immunosuppressive drug, widely used for organ
      transplantation and atopic dermatitis. Tacrolimus exerts its immunosuppressive
      effects primarily by interfering with the activation of T cells, via inhibition
      of calcineurin. Recent clinical studies have also demonstrated the efficacy of
      tacrolimus in the treatment of rheumatoid arthritis (RA), an autoimmune disease
      in which T cells play a pivotal role in pathogenesis. Inflammatory cytokines such
      as TNF-alpha, IL-1 beta, and IL-6 are involved in development of the disease.
      Recently, modes of action of tacrolimus on RA have been intensively studied in in
      vitro and animal arthritis models, demonstrating that tacrolimus exerts various
      novel actions as an anti-rheumatic drug. The pharmacological action of tacrolimus
      suggests that it has potential to specifically suppress the production of
      pathogenic inflammatory cytokines with a low frequency of infection, improve
      joint inflammation and bone/cartilage destruction, fully recover loss of
      functional status, exert rapid relief in arthritic pain, and promote osteogenic
      and chondrogenic differentiation. Here we review the action of tacrolimus on
      experimental models of RA, with a focus on our recent studies, and provide
      further insight into experimental models used for identifying efficacious anti
      rheumatic drugs.

PMID- 15723197
TI  - Sirolimus rescue of renal failure in children after combined liver-kidney
      transplantation.
AB  - BACKGROUND: Calcineurin inhibitors (CNI) are the main immunosuppressive drugs in
      solid organ transplantation. However, their use is hampered by side effects like
      nephrotoxicity. We report an exceptional experience with three children treated
      with sirolimus after combined liver and kidney transplantation with prolonged
      renal failure and CNI-associated nephrotoxicity. PATIENTS AND RESULTS: Two girls
      experienced prolonged renal graft failure after combined liver-kidney
      transplantation for 11 and 12 weeks. Repeated biopsies did not show any rejection
      but did exhibit tubular damage and acute CNI-toxicity. A boy with hyperoxaluria
      after liver and (a third) renal transplantation experienced acute renal graft
      failure after an early steroid-resistant rejection. All children were switched to
      sirolimus-based immunosuppression and cessation of CNI therapy, which was
      followed by rapid improvement of renal function. Rejection of liver or kidney did
      not occur after CNI withdrawal. Sirolimus was commenced with 3 mg/m2/day in two
      doses and resulted in reasonable drug exposure. However, drug monitoring was
      required to adjust sirolimus dosage. SUMMARY: Prolonged renal failure after
      transplantation with severe CNI toxicity may be salvaged successfully with
      sirolimus-based immunosuppression.

PMID- 15723200
TI  - Anti-inflammatory activity of PAS-1, a protein component of Ascaris suum.
AB  - BACKGROUND: Recently, we identified a 200 kDa protein (PAS-1) from Ascaris suum
      worms, that suppresses the humoral immune response. Here, the effect of PAS-1 on
      inflammatory leukocyte migration induced by bacterial lipopolysaccharide (LPS)
      was investigated. METHODS: Cellular migration and cytokine release, stimulated by
      LPS or LPS+PAS-1, were analyzed in air pouches induced in the shaved back of
      BALB/c mice. Cytokines were determined by ELISA and RT-PCR on air pouch exudates
      and in vitro stimulated peritoneal macrophages. RESULTS: The significant cellular
      influx induced by LPS, consisting predominantly of neutrophils, was highly
      suppressed in the presence of PAS-1, but not a non-related protein. PAS-1 led
      also to a marked reduction of TNF-alpha, IL-1 beta and IL-6 levels in both LPS
      stimulated air pouches and peritoneal macrophage cultures. In contrast, PAS-1
      induced a significant increase of IL-10 and TGF-beta production. CONCLUSIONS:
      These results demonstrate that PAS-1 has a potent anti-inflammatory activity,
      probably due to the stimulation of regulatory cytokines in macrophages, thus
      leading to the inhibition of pro-inflammatory cytokine production.

PMID- 15723199
TI  - Overlapping gene expression profiles in rheumatoid fibroblast-like synoviocytes
      induced by the proinflammatory cytokines interleukin-1 beta and tumor necrosis
      factor.
AB  - OBJECTIVE AND DESIGN: The development of therapies directed against TNF alpha and
      IL-1 beta has underscored the importance of these cytokines in rheumatoid
      arthritis (RA). In this study, oligonucleotide microarrays were used to identify
      novel transcriptional events mediated by TNF alpha and IL-1 beta. METHODS: In
      this study we have used Affymetrix U95A GeneChips representing 12,600 full-length
      human genes to identify transcriptional events mediated by these cytokines.
      Fibroblast-like synoviocytes were cultured from rheumatoid synovium from RA
      patients and stimulated with TNF alpha and IL-1 beta. Gene transcript levels were
      determined using Affymetrix U95A GeneChips representing 12,600 full-length human
      genes. RESULTS: A large number of differentially regulated genes were identified
      (1.7% of array-displayed genes for TNF alpha and 2.4% for IL-1 beta), and the
      validity of the array protocol was subsequently confirmed using real-time PCR.
      The majority of the differentially expressed genes were regulated by both TNF
      alpha and IL-1 beta, reflecting the distal signaling pathways shared by these
      cytokines. A large number of novel TNF alpha and IL-1 beta-regulated genes were
      identified. CONCLUSIONS: A panel of novel TNF alpha- and IL-1 beta-regulated
      genes was identified, and these are promising candidates for further study in
      relation to RA and other inflammatory diseases.

PMID- 15723201
TI  - Reduction of nickel-induced contact hypersensitivity reactions by topical tea
      tree oil in humans.
AB  - OBJECTIVE AND DESIGN: Whilst the anti-microbial properties of tea tree oil (TTO)
      are established, the anti-inflammatory effects of TTO in human skin remain
      largely anecdotal and require evaluation. This study examined the effect of
      topically applied TTO on nickel-induced contact hypersensitivity reactions in
      human dorsal skin. TREATMENT: TTO (100%), a 5% TTO lotion, a placebo lotion (no
      TTO), or 100% macadamia oil were applied at days 3 and 5 after nickel exposure.
      METHODS: The flare area and erythema index were measured on days 3, 5 and 7. The
      regulatory effects of TTO were also investigated on the proliferative response to
      nickel or polyclonal mitogens by peripheral blood mononuclear cells from nickel
      sensitive and control subjects. RESULTS: TTO (100%) significantly reduced the
      flare area and erythema index when compared to the nickel-only sites. With
      respect to the erythema index, the anti-inflammatory effects were predominantly,
      but not exclusively, seen in a subgroup of nickel-sensitive subjects with a
      prolonged development phase of nickel-induced contact hypersensitivity response.
      The 5% TTO lotion, the placebo lotion and the 100% macadamia oil were all without
      significant effect. TTO significantly inhibited proliferation to nickel but not
      to non-specific polyclonal mitogens by peripheral blood mononuclear cells from
      nickel-sensitive subjects. CONCLUSIONS: Topical application of 100% TTO may have
      therapeutic benefit in nickel-induced contact hypersensitivity in human skin. The
      mode of action of TTO requires further investigation, but may be an effect on the
      antigen presenting cells or the antigen presenting process in nickel-induced
      contact hypersensitivity, as well as vascular changes associated with this
      response.

PMID- 15723202
TI  - Increase in macrophage elastase (MMP-12) in lungs from patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE AND DESIGN: Chronic obstructive pulmonary disease (COPD) is
      characterized by an inflammatory process and airway remodeling involving matrix
      metalloproteinases (MMPs). Thus, we analyzed the expression and release of MMP-12
      (macrophage metalloelastase) in bronchoalveolar lavage (BAL) and lung tissue from
      COPD patients and control subjects. METHODS: Immunocytochemistry and
      immunochemistry were performed to analyze the expression of MMP-12 in BAL cells
      and bronchial biopsies. Western blotting was used for the evaluation of MMP-12 in
      BAL fluids. RESULTS: The number of MMP-12 expressing macrophages together with
      the staining intensity was higher in BAL samples from COPD patients than in
      controls subjects. Similar results were noted in bronchial biopsies with higher
      MMP-12 expression in COPD subjects than in controls. Enhanced MMP-12 level was
      also observed in BAL fluids from patient with COPD in comparison to control
      subjects. CONCLUSION: This study demonstrated that COPD patients produce greater
      quantities of MMP-12 than controls, which may be a critical step in the
      pathogenesis of COPD and emphysema.

PMID- 15723203
TI  - Rapid non-genomic inhibitory effects of glucocorticoids on human neutrophil
      degranulation.
AB  - BACKGROUND: Glucocorticoids acting as anti-inflammatory or immunosuppressive
      drugs have been shown to exert most of their effects genomically. Recent findings
      suggest that non-genomic activity might be relatively more important in mediating
      the therapeutic effects of high-dose pulsed glucocorticoid. However, few non
      genomic anti-inflammatory effects were reported, much less non-genomic
      mechanisms. OBJECTIVE: This study was performed to investigate the nongenomic
      effects of glucocorticoids on human neutrophil degranulation. METHODS: Purified
      human neutrophils were pretreated with 6 alpha-methylprednisolone or
      hydrocortisone for 5 min, and then primed with N-formyl-methionyl-leucyl
      phenylalanine (fMLP) (10(-6) M) or phorbol myristate acetate (PMA) (50 ng/ml) in
      the presence of cytochalasin B. The release of two markers of neutrophil
      granules, lactoferrin and myeloperoxidase, was measured by ELISA and enzymology
      methods respectively. RESULTS: Both 6 alpha-methylprednisolone (10(-5)-10(-4) M)
      and hydrocortisone (10(-4) M) showed significant inhibitory effects on neutrophil
      degranulation within 5 min after fMLP administration. For PMA stimulated
      degranulation, 6 alpha-methylprednisolone (10(-4) M) showed significant
      inhibitory effects (p < 0.01), while hydrocortisone (10(-4) M) only showed an
      inhibitory tendency (P > 0.05). Neither RU486 (10(-5) M) nor cycloheximide (10(
      4) M) could alter the inhibitory effects of glucocorticoids. CONCLUSION: Our
      results demonstrate that megadoses of glucocorticoids exert rapid inhibitory
      effects on human neutrophil degranulation at the cellular level via a new
      mechanism that is independent of corticosteroid type II receptor occupation or
      protein synthesis. We infer that these effects may be very important when
      glucocorticoids act as anti-inflammatory drugs during pulse therapy.

PMID- 15723204
TI  - Is there a role of taurine bromamine in inflammation? Interactive effects with
      nitrite and hydrogen peroxide.
AB  - OBJECTIVE AND DESIGN: The myeloperoxidase system of neutrophils generates
      chlorinating and brominating oxidants in vivo. The major haloamines of the system
      are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been
      demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial
      properties. Much less is known about TauBr. The present study was conducted to
      compare bactericidal and immunoregulatory capacity of TauBr with that of the
      major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and
      H(2)O(2) on TauBr activity was investigated. MATERIALS: TauBr was prepared by
      reaction of HOBr with taurine. The reaction was monitored by UV absorption
      spectra. METHODS: Bactericidal activity of TauBr, TauCl and HOCl was tested by
      incubation of E. coli with the compounds and determined by the pour-plate method.
      To test the anti-inflammatory activity the compounds were incubated with LPS and
      IFN-gamma stimulated murine peritoneal macrophages. The production of following
      mediators was measured: nitrites by Griess reaction; TNF-alpha, IL-6, IL-10, IL
      12p40 using capture ELISA. In some experiments the compounds were incubated with
      either nitrites or H(2)O(2). RESULTS: In our experimental set-up TauBr and HOCl
      exerted strong bactericidal effects on E. coli (MBC = 110 microM and 8 microM,
      respectively), while TauCl (< 1000 microM) did not kill test bacteria. However,
      both, TauBr and TauCl, at noncytotoxic concentrations (< 300 microM) inhibited
      the cytokine and nitric oxide production by macrophages. H(2)O(2) completely
      abolished the biological activities of TauBr but not those of TauCl. Nitrites did
      not affect any activity of TauBr or TauCl while they diminished the HOCl(-)
      mediated bacterial killing. CONCLUSION: TauBr, despite very low concentration of
      Br(-) in body fluids, may support TauCl and HOCl in the regulation of
      inflammatory response and in killing of bacteria by neutrophils. However, TauBr
      activity in vivo will depend on the presence of H(2)O(2) and possible other
      mediators of inflammation which can compete with target molecules for TauBr.

PMID- 15723205
TI  - The cancer pain experience of Israeli adults 65 years and older: the influence of
      pain interference, symptom severity, and knowledge and attitudes on pain and pain
      control.
AB  - GOALS: Little is known about Israeli elders' cancer pain experience. The purpose
      of this study was to explore the cancer pain experience, including pain
      intensity, pain management index, pain interference, symptom severity, and
      knowledge and attitudes toward pain and pain control. PATIENTS AND METHODS:
      Descriptive cross-sectional methods were used to obtain data with four
      instruments. The patients were 39 Israelis 65 years and older who were receiving
      outpatient treatment for cancer in a major hospital center in Israel. RESULTS:
      Results showed that over half (56.7%) reported severe worst pain and had negative
      pain management indexes (56.4%). In addition, knowledge and attitudes toward pain
      and pain control were poor (54.55%). There were no significant relationships
      between pain intensity and other variables. However, pain interference
      demonstrated a significant positive relationship with symptom severity. Post hoc
      analysis revealed that Ashkenazi Jewish and more educated patients reported
      significantly less pain interference than Sephardic Jewish patients. CONCLUSION:
      Larger samples representative of the cultural differences in Israel are needed to
      more definitively identify elements of the cancer pain experience in Israeli
      elders that can be addressed to improve pain management.

PMID- 15723206
TI  - The intrinsic axial ligand effect on propene oxidation by horseradish peroxidase
      versus cytochrome P450 enzymes.
AB  - The axial ligand effect on reactivity of heme enzymes is explored by means of
      density functional theoretical calculations of the oxidation reactions of propene
      by a model compound I species of horseradish peroxidase (HRP). The results are
      assessed vis-a-vis those of cytochrome P450 compound I. It is shown that the two
      enzymatic species perform C=C epoxidation and C-H hydroxylation in a multistate
      reactivity scenario with Fe(III) and Fe(IV) electromeric situations and two
      different spin states, doublet and quartet. However, while the HRP species
      preferentially keeps the iron in a low oxidation state (Fe(III)), the cytochrome
      P450 species prefers the higher oxidation state (Fe(IV)). It is found that HRP
      compound I has somewhat lower barriers than those obtained by the cytochrome P450
      species. Furthermore, in agreement with experimental observations and studies on
      model systems, HRP prefers C=C epoxidation, whereas cytochrome P450 prefers C-H
      hydroxylation. Thus, had the compound I species of HRP been by itself, it would
      have been an epoxidizing agent, and at least as reactive as cytochrome P450. In
      the enzyme, HRP is much less reactive than cytochrome P450, presumably because
      HRP reactivity is limited by the access of the substrate to compound I.

PMID- 15723207
TI  - Semi-empirical topological index: a tool for QSPR/QSAR studies.
AB  - The semi-empirical topological index (I(ET)), developed to predict the
      chromatographic retention of a series of organic compounds, is extended to
      predict other properties and biological activities of aliphatic alcohols. This
      topological index takes into account the contribution of each individual atom
      type to the property considered and is able to encode information about
      structural features of the molecules. The efficiency of this index is verified by
      high quality Structure - Property and structure - Activity Relationships
      (QSPR/QSAR) models obtained for several representative physicochemical
      properties, biological activities and toxicities of aliphatic alcohols. Most of
      the properties investigated are well modeled (r > 0.98) employing the I(ET).
      Cross-validation using the more general leave-one-out method demonstrates that
      these models are highly statistically reliable. The proposed I(ET) index promises
      to be a useful descriptor in the QSPR/QSAR studies.

PMID- 15723208
TI  - Markovian chemicals "in silico" design (MARCH-INSIDE), a promising approach for
      computer-aided molecular design III: 2.5D indices for the discovery of
      antibacterials.
AB  - The present work continues our series on the use of MARCH-INSIDE molecular
      descriptors (parts I and II: J Mol Mod 8:237-245, [2002] and 9:395-407, [2003]).
      These descriptors encode information pertaining to the distribution of electrons
      in the molecule based on a simple stochastic approach to the idea of
      electronegativity equalization (Sanderson's principle). Here, 3D-MARCH-INSIDE
      molecular descriptors for 667 organic compounds are used as input for a linear
      discriminant analysis. This 2.5D-QSAR model discriminates between antibacterial
      compounds and non-antibacterial ones with 92.9% accuracy in training sets. On the
      other hand, the model classifies 94.0% of the compounds in test set correctly.
      Additionally, the present QSAR performs similar-to-better than other methods
      reported elsewhere. Finally, the discovery of a novel compound illustrates the
      use of the method. This compound, 2-bromo-3-(furan-2-yl)-3-oxo-propionamide has
      MIC50 of 6.25 and 12.50 microg/mL against Pseudomonas aeruginosa ATCC 27853 and
      Escherichia coli ATCC 27853, respectively while ampicillin, amoxicillin,
      clindamycin, and metronidazole have, for instance, MIC50 values higher than 250
      mug/mL against E. coli. Consequently, the present method may becomes a useful
      tool for the in silico discovery of antibacterials.

PMID- 15723209
TI  - Periosteal chondrosarcoma in a 9-year-old girl with osteochondromatosis.
AB  - A 9-year-old girl with multiple osteochondromatosis presented with a 1 year
      history of a gradually enlarging surface lesion originating from the midsection
      of the right humerus, distal to an osteochondroma. Radiographically and
      histologically this lesion proved to be a periosteal chondrosarcoma adjacent to
      an osteochondroma.

PMID- 15723211
TI  - Bilateral multiple malignant transformation of Ollier's disease.
AB  - We treated a 26-year-old man with a 19-year history of Ollier's disease.
      Secondary chondrosarcomas developed metachronously at four separate locations:
      both femora, left proximal tibia and fibular head. All four lesions were
      surgically excised, and each specimen was histologically identified as grade 1 or
      2 chondrosarcoma. Clinical follow-up for 20 years beginning at the time of first
      tumor surgery has shown no evidence of local recurrence or metastasis. This is
      the first report of multiple bilateral metachronous malignant transformation of
      multiple chondromatoses in a patient with Ollier's disease.

PMID- 15723210
TI  - Multiple congenital cranial hemangiomas.
AB  - Though cranial hemangiomas are second only to vertebral hemangiomas in frequency,
      such lesions are rarely congenital and multiple. It is probable that the true
      incidence of congenital calvarial hemangiomas is higher than that reported in the
      literature, as they are unlikely to undergo imaging, most being asymptomatic and
      without a significant soft tissue component. We present a case of multiple
      congenital calvarial and skull base cavernous-type hemangiomas, diagnosed in a 4
      day-old female, involving the right zygoma, maxilla, frontal and petrous temporal
      bones and contralateral squamous temporal bone. Surgical biopsy confirmed the
      radiological diagnosis as well as the concomitant multiple subcutaneous capillary
      type hemangiomas which were identified clinically. No specific clinical syndrome
      or chromosomal abnormality was identified and the underlying cerebral parenchyma
      was normal with no intra-axial involvement. With conservative treatment, two
      lesions completely resolved and a further two lesions subsequently decreased in
      both size and degree of enhancement. To the best of our knowledge, this is the
      first case of multiple congenital hemangiomas involving the calvarium and skull
      base. Despite this, the radiological features, combined with the clinical
      findings of multiple capillary hemangiomas, were characteristic enough to permit
      an accurate preoperative diagnosis. Osseous hemangiomas should feature
      prominently in any differential diagnosis of multiple hypervascular lesions, as
      they are common, more so when limited to an anatomical region, irrespective of
      site or age.

PMID- 15723212
TI  - Acromioclavicular joint cyst: nine cases of a pseudotumor of the shoulder.
AB  - OBJECTIVE: (1) To analyse the imaging appearances of nine patients with
      acromioclavicular joint cysts presenting as shoulder masses for tumor staging
      with operative, histopathological and joint aspiration findings. DESIGN AND
      PATIENTS: Retrospective review of imaging and correlation with clinical,
      operative and surgical notes. Images were reviewed by two musculoskeletal
      radiologists by consensus. Nine patients who presented clinically with a shoulder
      mass were evaluated by radiographs (n=9), ultrasound (n=1), conventional
      arthrography (n=3), MRI (n=6; with direct MR arthrography n=2, indirect MR
      arthrography n=4). RESULTS: All patients had a focal mass superior to the AC
      joint, with a size ranging from 1.5 cm to 6 cm and a mean of 3.27 cm. Correlation
      was available with surgery (n=7), histopathology (n=2) and cyst aspiration (n=2).
      Two patients were managed conservatively. Geyser sign was positive in all three
      arthrograms. All MRIs revealed extensive rotator cuff tears with a column of
      fluid extending from the glenohumeral joint through the rotator cuff tear into
      the acromioclavicular joint and acromioclavicular cyst. Chondrocalcinosis was
      seen in the acromioclavicular joint cyst (n=2) and in the glenohumeral joint
      (n=1). Aspirate in two patients contained calcium pyrophosphate dihydrate
      crystals. CONCLUSION: Acromioclavicular joint cysts may present as a tumor mass.
      They are associated with extensive rotator cuff tears and there is usually
      communication of the cyst with the joint space. This feature excludes a diagnosis
      of tumor. AC joint cysts may be associated with calcium pyrophosphate dihydrate
      deposition disease.

PMID- 15723213
TI  - Asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate with
      Lactobacillus kefir.
AB  - An efficient whole cell biotransformation process using Lactobacillus kefir was
      developed for the asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro
      dihydroxyhexanoate, a chiral building block for the HMG-CoA reductase inhibitor.
      The effects of buffer concentration, temperature, pH and oxygen on the asymmetric
      reduction were investigated in batch reactions. Improvements in final product
      concentration and yields of 153% (120 mM) and 79% (0.85 mol/mol) with respect to
      the batch-process were achieved in an optimised fed-batch process. The pure
      substrate tert-butyl-6-chloro-3,5-dioxohexanoate was dispersed as microdroplets
      into the reaction system. This resulted in a space-time yield of 4.7 mmol l(-1)
      h(-1). A diastereomeric excess of >99% was measured for (3R, 5S) and (3S, 5S)
      tert-butyl 6-chloro-dihydroxyhexanoate.

PMID- 15723214
TI  - Sixteen multidetector row computed tomography of pulmonary veins: 3-months'
      follow-up after treatment of paroxysmal atrial fibrillation with cryothermal
      ablation.
AB  - The aim of the study was to assess pulmonary veins (PVs) for the presence of
      stenosis 3 months after cryothermal ablation (CA) with a new method of electrical
      isolation of PVs using contrast-enhanced 16 multidetector row computed tomography
      (MDCT). Twenty four patients with symptomatic atrial fibrillation underwent CA in
      46 PVs. MDCT of PVs was performed before the treatment and after 3-months' follow
      up. Following cryoablation, 13/24 (54%) patients showed clinical improvement and
      had reduced attacks of atrial fibrillation. The dimensions of the treated PVs
      remained unchanged: the coronal ostial diameter was 19.1+/-2.4 preprocedural
      versus 18.6+/-2.4 mm at follow-up, p>0.05; the ratio of the coronal and axial
      diameters at the ostium was 1.2+/-0.2 versus 1.2+/-0.1, p>0.05, respectively, and
      the coronal diameter of the proximal 10 mm was 17.1+/-2.5 mm versus 16.5+/-2.2
      mm, p>0.05, respectively. CA is a promising technique for electrical isolation of
      PVs that has not been associated with stenosis at the orifice and the proximal 10
      mm of the PVs after 3-months' follow-up. MDCT is a noninvasive, fast and
      comfortable method for assessment of PVs in a three-dimensional manner prior to
      ablative treatment and during the follow-up.

PMID- 15723216
TI  - Determinants of lumbar artery occlusion among patients with sciatica: a three
      year follow-up with magnetic resonance angiography.
AB  - We showed previously that chronic Chlamydia pneumoniae infection increases the
      risk of lumbar artery occlusion. We did not evaluate, however, the effect of
      other risk factors for cardiovascular diseases in combination with this chronic
      infection. The purpose of this study was to investigate the combined effect of
      chronic C. pneumoniae infection and other known determinants of artery occlusion
      in a population of sciatica patients. Two-dimensional time-of-flight magnetic
      resonance angiography (MRA) was used to evaluate lumbar arteries at baseline and
      three years. The arteries on both sides (L1-L4) were evaluated visually and
      scored as normal, narrowed or occluded. Logistic regression analysis was
      performed separately for baseline total arterial stenosis and each L1-L4
      segmental artery pair, and for incident new stenosis during the follow-up period.
      The determinants analyzed included age, body mass index (BMI, kg/m(2)),
      education, gender, and smoking, in addition to presence of chronic C. pneumoniae
      infection. MRA was obtained at baseline for 147 patients and at 3 years for 134
      patients. Sixty-four (47.8%) of 134 patients had new arterial stenosis. Total
      incidence of new arterial stenosis was distributed quite evenly between the
      individual segmental levels, varying from 12.7 to 18.6%. BMI was the only
      predictor of new arterial stenosis (odds ratio (OR) 1.13). A reasonable logistic
      model could be established only for baseline L4 and total arterial scores. At L4,
      education was a protective factor (OR 0.07), whereas age (OR for the oldest age
      group 6.7) and BMI (OR 1.17) were associated with increased risk of occlusion.
      For total arterial score, chronic C. pneumoniae infection was an independent
      determinant of arterial occlusion, increasing the risk to almost eightfold.
      Additionally, BMI (OR 1.16), and age (for the oldest age group OR 11.4) were
      significant determinants for stenosis. Smoking was not statistically significant.
      As chronic C. pneumoniae infection was an independent determinant of lumbar
      artery occlusion, treatments of this chronic infection may have an impact on
      lumbar diseases. The importance of BMI for new arterial stenosis suggests that
      weight reduction may also have a beneficial effect in lumbar artery disease.

PMID- 15723215
TI  - Magnetic resonance imaging of atherosclerosis.
AB  - Abundant data now link composition of the vascular wall, rather than the degree
      of luminal narrowing, with the risk for acute ischemic syndromes in the coronary,
      central nervous system, and peripheral arterial beds. Over the past few years,
      magnetic resonance angiography has evolved as a well-established method to
      determine the location and severity of advanced, lumen-encroaching
      atherosclerotic lesions. In addition, more recent studies have shown that high
      spatial resolution, multisequence MRI is also a promising tool for noninvasive,
      serial imaging of the aortic and carotid vessel wall, which potentially can be
      applied in the clinical setting. Because of the limited spatial resolution of
      current MRI techniques, characterization of coronary vessel wall atherosclerosis,
      however, is not yet possible and remains the holy grail of plaque imaging. Recent
      technical developments in MRI technology such as dedicated surface coils, the
      introduction of 3.0-T high-field systems and parallel imaging, as well as
      developments in the field of molecular imaging such as contrast agents targeted
      to specific plaque constituents, are likely to lead to the necessary improvements
      in signal to noise ratio, imaging speed, and specificity. These improvements will
      ultimately lead to more widespread application of this technology in clinical
      practice. In the present review, the current status and future role of MRI for
      plaque detection and characterization are summarized.

PMID- 15723217
TI  - Multidetector-row computed tomography three-dimensional volume reformatted
      'transparency' images to define an upper pouch fistula in oesophageal atresia.
AB  - Oesophageal atresia (OA) is an important congenital malformation in which prompt
      diagnosis and appropriate management can significantly improve outcome. The
      surgical approach to repair of OA and associated tracheo-oesophageal fistulae
      (TOF) depends upon correct evaluation of the tracheobronchial tree. Three
      dimensional imaging of the tracheobronchial tree using CT data to produce shaded
      surface displays and virtual bronchoscopy has been reported in paediatric and
      neonatal patients with OA and TOF and is described as accurate and helpful, non
      invasively facilitating the appreciation of complex anatomy prior to surgery. We
      describe the technique of reconstructing 3D volume-reformatted 'transparency'
      images using insufflated air as a negative contrast medium. This technique is
      fast, accurate and produces high-quality images that are easy to reproduce.

PMID- 15723218
TI  - Paraneoplastic limbic encephalitis in a teenage girl with an immature ovarian
      teratoma.
AB  - Paraneoplastic limbic encephalitis (PLE) is an unusual disorder that is
      characterized by the association of clinical limbic system abnormalities with
      neoplasia, usually malignancy. It has rarely been reported in children and then
      manifests during the teenage years. Diagnosis is often delayed, especially when
      the tumor has not been recognized. In adults, the diagnosis can be revealed by
      the presence of antineuronal antibodies. We describe an unusual case of
      behavioral disturbance leading rapidly to coma in a 14-year-old girl with CSF
      pleocytosis who was found 10 weeks later to have an immature ovarian teratoma.
      Although her symptoms eventually improved slightly after tumor excision, she died
      while in rehabilitation. PLE is an important diagnosis to consider in the teenage
      girl with symptoms of a progressive limbic disorder and CSF pleocytosis, and
      whose brain MR imaging demonstrates no abnormality or mild T2-weighted temporal
      lobe signal abnormality. When this constellation of findings presents in a
      teenage girl, the possibility of an underlying ovarian teratoma should be
      considered.

PMID- 15723219
TI  - Gefitinib (Iressa, ZD1839) inhibits SN38-triggered EGF signals and IL-8
      production in gastric cancer cells.
AB  - Epidermal growth factor receptor (EGFR) and its ligands are involved in tumor
      growth, metastasis, angiogenesis, and resistance to chemotherapy. In the
      experiments described here using AGS gastric cancer cells, SN38 (the active
      metabolite of CPT-11) induced tyrosine phosphorylation of EGFR within 5 min, and
      this was followed by the induction of transcripts and/or proteins of heparin
      binding EGF-like growth factor, amphiregulin, transforming growth factor-alpha,
      and interlukin-8 (IL-8). SN38 also activates nuclear factor-kappaB and activator
      protein-1, both of which are critical for the transcription of the IL-8 gene.
      However, the blocking of EGFR activation by gefitinib (Iressa, ZD1839), an EGFR
      TKI (tyrosine kinase inhibitor), abrogates all the above reactions. The SN38
      triggered mechanisms include the generation of reactive oxygen species (ROS) and
      the activation of protein kinase C (PKC), followed by metalloproteinase
      activation and the sequential ectodomain shedding of EGFR ligands. These findings
      suggest that EGF signaling is enhanced by CPT-11 and point to the potential
      benefit of the use of a combination of CPT-11 with gefitinib in the treatment of
      certain gastric cancers.

PMID- 15723221
TI  - Targeting Bcl-2 with oblimersen for patients with hormone refractory prostate
      cancer.
AB  - Patients with metastatic hormone refractory prostate cancer (HRPC) have limited
      treatment options and new therapies are needed. Advances in the understanding of
      the molecular mechanisms implicated in prostate cancer progression have
      identified many potential therapeutic gene targets including Bcl-2, an important
      pro-survival regulator of apoptotic cell death. Bcl-2 is overexpressed in a
      variety of human malignancies including prostate cancer where it has also been
      associated with androgen independent progression and treatment resistance.
      Oblimersen is a phosphorothioate antisense oligonucleotide complimentary to the
      Bcl-2 mRNA and a potent inhibitor of Bcl-2 expression which in pre-clinical
      testing can significantly enhance the therapeutic effect of chemotherapy, hormone
      and radiation therapy. Clinical trials evaluating oblimersen in combination with
      chemotherapy in a variety of cancers have shown good tolerability and promising
      response rates. Randomized trials are required to determine if oblimersen can
      enhance the effectiveness of docetaxel in patients with HRPC.

PMID- 15723222
TI  - Duodenal duplication cyst communicating with an aberrant pancreatic duct.
AB  - Duodenal duplication cyst (DDC) is an uncommon congenital anomaly and is the
      rarest site for intraabdominal duplications. We report a case of DDC
      communicating with an aberrant pancreatic duct in a 2-year-old girl, with
      features of possible occult relapsing pancreatitis. The duplication cyst was
      successfully enucleated with excision of the aberrant pancreatic duct. The
      literature is reviewed, and the diagnostic modalities and management options are
      discussed.

PMID- 15723220
TI  - Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer
      patients.
AB  - BACKGROUND: Aprepitant is a selective neurokinin-1 receptor antagonist that is
      effective for the prevention of nausea and vomiting caused by highly emetogenic
      chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme,
      which is involved in the clearance of several chemotherapeutic agents. In this
      study we examined the potential for aprepitant to affect the pharmacokinetics and
      toxicity of intravenously administered docetaxel, a chemotherapeutic agent that
      is primarily metabolized by CYP3A4. METHODS: A total of 11 cancer patients (4
      male, 7 female, aged 50-68 years) were enrolled in this multicenter, randomized,
      open-label, two-period, crossover study. Patients received a single infusion of
      docetaxel monotherapy, 60-100 mg/m(2), on two occasions at least 3 weeks apart.
      During one of the cycles (treatment A), patients received docetaxel alone. During
      the alternate cycle (treatment B), they also received aprepitant 125 mg orally 1
      h prior to docetaxel infusion (day 1), and a single oral dose of aprepitant 80 mg
      on days 2 and 3. The pharmacokinetic profile of docetaxel was assessed over 30 h
      following docetaxel infusion. Blood counts were monitored on days 1, 4, 7, and
      14. RESULTS: Ten patients completed the study. Concomitant administration of
      aprepitant did not cause any statistically or clinically significant changes in
      docetaxel pharmacokinetics. Values for docetaxel alone (treatment A) versus
      docetaxel with aprepitant (treatment B) were as follows: geometric mean AUC(0
      last) was 3.26 vs 3.17 microg h/ml (P>0.25; ratio B/A 0.97); geometric mean AUC(0
      infinity) 3.51 vs 3.39 microg h/ml (P>0.25; ratio B/A 0.96); geometric mean
      C(max) was 3.53 vs 3.37 microg/ml (P>0.25; ratio B/A 0.95); and geometric mean
      plasma clearance was 23.3 vs 24.2 l/h/m(2) (P>0.25; ratio B/A 1.04). The
      corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two
      treatment regimens had similar tolerability profiles; the median absolute
      neutrophil count nadirs were 681/mm(3) during treatment with docetaxel alone and
      975/mm(3) during aprepitant coadministration. CONCLUSIONS: Aprepitant had no
      clinically significant effect on either the pharmacokinetics or toxicity of
      standard doses of docetaxel in cancer patients. Aprepitant at clinically
      recommended doses may have a low potential to affect the pharmacokinetics of
      intravenous chemotherapeutic agents metabolized by CYP3A4.

PMID- 15723223
TI  - Effects of over-expression of the regulatory enzymes DraT and DraG on the
      ammonium-dependent post-translational regulation of nitrogenase reductase in
      Azospirillum brasilense.
AB  - Nitrogen fixation in Azospirillum brasilense is regulated at transcriptional and
      post-translational levels. Post-translational control occurs through the
      reversible ADP-ribosylation of dinitrogenase reductase (Fe Protein), mediated by
      the dinitrogenase reductase ADP-ribosyltransferase (DraT) and dinitrogenase
      reductase glycohydrolase (DraG). Although the DraT and DraG activities are
      regulated in vivo, the molecules responsible for such regulation remain unknown.
      We have constructed broad-host-range plasmids capable of over-expressing, upon
      IPTG induction, the regulatory enzymes DraT and DraG as six-histidine-N-terminal
      fused proteins (His). Both DraT-His and DraG-His are functional in vivo. We have
      analyzed the effects of DraT-His and DraG-His over-expression on the post
      translational modification of Fe Protein. The DraT-His over-expression led to Fe
      Protein modification in the absence of ammonium addition, while cells over
      expressing DraG-His showed only partial ADP-ribosylation of Fe Protein by adding
      ammonium. These results suggest that both DraT-His and DraG-His lose their
      regulation upon over-expression, possible by titrating out negative regulators.

PMID- 15723225
TI  - Premature conclusions may harm good ideas.

PMID- 15723226
TI  - Development and validation of a novel HPLC/ELSD method for the direct
      determination of tobramycin in pharmaceuticals, plasma, and urine.
AB  - A novel method for the direct determination of the aminoglycoside tobramycin was
      developed and validated based on reversed-phase high-performance liquid
      chromatography (RP-HPLC) with evaporative light scattering detector (ELSD). Using
      a Waters ODS-2 C18 Spherisorb column with an evaporation temperature of 45
      degrees C and nitrogen pressure of 3.5 bar, the selected mobile phase consisted
      of water/acetonitrile 55:45 containing 1.5 mL L(-1) HFBA (11.6 mM) in an
      isocratic mode at a rate of 1.0 mL min(-1). Tobramycin's retention time was 4.3
      min with an asymmetry factor of 1.7. A logarithmic calibration curve was obtained
      from 1 to 38 microg mL(-1) (r > 0.9998). LOD was 0.3 microg mL(-1); within-day
      %RSD was 1.0 (n = 3, 4.7 microg mL(-1)) and between-day %RSD was 1.1 (3 days
      within a week). The developed method was applied to the determination of
      tobramycin in a pharmaceutical crude substance and formulations (eye drops and
      ointments). Dilution experiments revealed the absence of interference from
      excipients (no constant and proportional errors); recovery from spiked samples
      was 99-103% with %RSD < 2.2 (n = 3x3). The developed HPLC/ELSD method was also
      found to be applicable in the determination of tobramycin in human plasma (0.6
      12.5 microg mL(-1)) and urine (1.5-12.5 microg mL(-1)) after solid-phase
      extraction using carboxylate cartridges followed by solvent evaporation (x2
      preconcentration). A mean recovery of 86% for plasma and 91% for urine was
      obtained.

PMID- 15723227
TI  - The effect of caffeine on cognitive task performance and motor fatigue.
AB  - RATIONALE: In everyday life, people are usually capable of performing two tasks
      simultaneously. However, in a previous study we showed that during a fatiguing
      motor task, cognitive performance declined progressively. There is extensive
      literature on the (positive) effects of caffeine on cognitive and motor
      performance. These effects are most pronounced under suboptimal conditions, for
      example during fatigue. However, little is known about the effects of caffeine on
      cognitive performance during a fatiguing motor task. OBJECTIVE: This study was
      aimed to investigate whether a moderate dose of caffeine could attenuate the
      decline in cognitive performance during a fatiguing motor task. METHODS: The
      study consisted of a placebo and a caffeine (3 mg/kg) session. A total of 23
      subjects completed these sessions in a semi-randomized and double-blind order. In
      each session, subjects performed maximal voluntary contractions of the index
      finger, a choice reaction time (CRT) task and a dual task consisting of a
      fatiguing motor task concomitantly with the same CRT task. After the fatiguing
      dual task, the CRT task was repeated. RESULTS: Caffeine improved cognitive task
      performance, in both the single and dual task, as shown by decreased reaction
      times together with unchanged accuracy. Cognitive performance in the dual task
      deteriorated with increasing fatigue. However, the decrease in cognitive
      performance in the beginning of the dual task, as observed in the placebo
      condition, was partly prevented by caffeine administration (i.e., no increase in
      reaction times). We found no effects of caffeine on motor parameters (absolute
      force, endurance time or electromyographic amplitude). CONCLUSIONS: Caffeine
      improved cognitive performance. This effect also extends under demanding
      situations, as was shown by the performance during the dual task, even during
      progressive motor fatigue.

PMID- 15723228
TI  - Tolerance to nicotine in mice lacking alpha7 nicotinic receptors.
AB  - RATIONALE: Previous studies have suggested that a knockout of the gene coding for
      alpha7 nicotinic receptor subunits influences the behaviour of undrugged mice but
      not the acute effect of nicotine on locomotor activity. OBJECTIVES: The present
      studies extend these observations to nicotine tolerance assessed by means of
      schedule-controlled behaviour. METHODS: Groups of alpha7-/- and alpha7+/+ mice
      were trained to press levers under an FR20 schedule of food reinforcement. The
      acute response rate-depressant effects of nicotine were determined in both
      genotypes and the mice were then subdivided into groups treated daily with
      nicotine (1.2 mg/kg/day) or saline. After 39 days of exposure to this regimen,
      the dose-response curves were re-determined. RESULTS: Knockout of the alpha7 gene
      had no consistent effect on the lever-pressing behaviour of undrugged mice and
      did not influence the acute, dose-related, response rate-depressant effect of
      nicotine (0.2-1.2 mg/kg). When dose-response curves for nicotine (0.4-2.0 mg/kg)
      were re-determined after daily dosing with the drug, both wild-type and knockout
      mice developed similar tolerance to nicotine, as shown by approximately 2.5-fold
      shifts to the right of the dose-response curves. CONCLUSIONS: Nicotinic receptors
      containing the alpha7 subunit do not play a significant role in the regulation of
      the lever-pressing behaviour studied or in the acute behavioural depressant
      effect of nicotine and the development of tolerance to that effect. Such results
      contrast with previous reports suggesting profound impairments in sensitivity to
      nicotine in nicotinic receptor beta2-/- mice.

PMID- 15723229
TI  - Plasma corticosterone in the rat in response to nicotine and saline injections in
      a context previously paired or unpaired with nicotine.
AB  - RATIONALE: Following repeated injections with nicotine paired with a distinctive
      environment, some studies have reported that the distinctive context becomes a
      conditioned stimulus (CS) capable of eliciting conditioned corticosterone (CORT)
      release. Conversely, other studies have found that exposure to the CS results in
      conditioned attenuation of nicotine-induced CORT release. OBJECTIVE: The present
      study was designed to examine whether these sets of separate findings could be
      replicated in animals exposed to the same experimental procedures within the same
      study. METHODS: CORT assessments were conducted in a distinctive context after
      independent groups of animals were injected with either saline or nicotine (1
      mg/kg, salt) after five or ten nicotine injections either explicitly paired or
      unpaired with a distinctive context. The design also included groups of nicotine
      naive rats exposed to the experimental procedures and assessed for CORT levels
      following either nicotine or saline injections during their first, and after
      their fifth and tenth context exposures. RESULTS: CORT levels were higher after
      nicotine than after saline, and higher in the paired than in the unpaired
      condition. Exposure to the context without nicotine produced conditioned CORT
      release and exposure to the context did not attenuate nicotine-induced CORT
      release. CONCLUSIONS: The results supported the notion that a CS associated with
      nicotine effects elicit a conditioned response (CR) in the form of CORT release.
      Future research will be needed to examine whether conditioned CORT release can
      explain the context-dependent attenuations of nicotine-induced CORT.

PMID- 15723230
TI  - Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2
      receptor-mediated effects in the rat and implications for psychosis.
AB  - RATIONALE: The effect of LSD in humans has been described as occurring in two
      temporal phases. The behavioral effects in rats also occur in two temporal
      phases: an initial suppression of exploration followed by increased locomotor
      activity. OBJECTIVES: We decided to investigate this phenomenon from the
      perspective that the pharmacology might have relevance to the neurochemical
      mechanisms underlying psychosis. METHODS: Twenty-five male Sprague-Dawley rats
      were trained to discriminate LSD (186 nmol/kg, 0.08 mg/kg, i.p.) with a 30-min
      preinjection time (LSD-30, N=12) and LSD (372 nmol/kg, 0.16 mg/kg, i.p.) with a
      90-min preinjection time (LSD-90, N=13) from saline, using a two-lever, food
      reinforced operant conditioning task. RESULTS: LSD (186 or 372 nmol/kg, 0.08 or
      0.16 mg/kg) given 30 min prior to training produced a cue that was completely
      antagonized by 5-HT2A antagonists and lasted no longer than 1 h. LSD (372
      nmol/kg, 0.16 mg/kg) injected 90 min before training produced a cue that was not
      fully blocked by 5-HT2A antagonists, but instead was significantly inhibited by
      haloperidol. In these rats, substitution no longer occurred with the 5-HT2
      agonists DOI or LSD (30 min preinjection), but full substitution was obtained
      with the D2 agonists apomorphine, N-propyldihydrexidine, and quinelorane.
      CONCLUSION: The discriminative stimulus effect of LSD in rats occurs in two
      phases, and these studies provide evidence that the later temporal phase is
      mediated by D2 dopamine receptor stimulation. A second temporal phase that
      involves dopaminergic pathways would be consistent with the widespread belief
      that excessive dopaminergic activity may be an underlying cause of paranoid
      psychosis.

PMID- 15723232
TI  - Congenital supratentorial meningeal arteriovenous malformation with hemangioma
      and massive arachnoid cell hyperplasia.
AB  - CASE REPORT: We describe the clinical, radiological and pathological findings of
      concurrent, congenital leptomeningeal arteriovenous malformation with hemangioma
      diagnosed in a newborn by prenatal and immediately postnatal magnetic resonance
      imaging. Vascular abnormalities were accompanied by massive arachnoidal cell
      hyperplasia reminiscent of meningioma. CONCLUSION: To the best of our knowledge,
      this is the first case of such a lesion reported in the literature.

PMID- 15723231
TI  - Impaired perception of self-motion (heading) in abstinent ecstasy and marijuana
      users.
AB  - RATIONALE: Illicit drug use can increase driver crash risk due to loss of control
      over vehicle trajectory. This study asks, does recreational use of +/-3,4
      Methylenedioxymethamphetamine (MDMA; ecstasy) and tetrahydrocannabinol (THC;
      marijuana) impair cognitive processes that help direct our safe movement through
      the world? OBJECTIVE: This study assesses the residual effects of combined
      MDMA/THC use, and of THC use alone, upon perceived trajectory of travel. METHODS:
      Perception of self-motion, or heading, from optical flow patterns was assessed
      using stimuli comprising random dot ground planes presented at three different
      densities and eight heading angles (1, 2, 4 and 8 degrees to the left or right).
      On each trial, subjects reported if direction of travel was to the left or the
      right. RESULTS: Results showed impairments in both drug groups, with the MDMA/THC
      group performing the worst. CONCLUSIONS: The finding that these psychoactive
      agents adversely affect heading perception, even in recently abstinent users,
      raises potential concerns about MDMA use and driving ability.

PMID- 15723233
TI  - A diagnostic score for children with suspected appendicitis.
AB  - BACKGROUND/PURPOSE: Appendicectomy is an operation that is often performed
      without certainty of diagnosis. This study aimed to construct and to validate a
      prognostic score for the diagnosis of acute appendicitis in children. METHODS:
      Data for 35 symptoms and signs were prospectively recorded for 131 consecutive
      children with suspected appendicitis. Logistic regression analysis of the
      variables yielded a diagnostic score: gender (male 2 points, female 0) +
      intensity of abdominal pain (severe 2, mild or moderate 0) + relocation of pain
      (yes 4, no 0) + vomiting (yes 2, no 0) + pain in the right lower abdominal
      quadrant (yes 4, no 0) + fever (yes 3, no 0) + guarding (yes 4, no 0) + bowel
      sounds (abnormal 4, normal 0) + rebound tenderness (yes 7, no 0). The cut-off
      level for recommendation of appendicectomy was > or =21, and the cut-off level
      for non-appendicitis was < or =15. The score was prospectively validated on 109
      children. RESULTS: In the validation sample, based on clinical judgment,
      unnecessary appendicectomy was performed in ten (27%) children, and one (4%)
      child was misdiagnosed as not having appendicitis. By application of the score,
      unnecessary appendicectomies would have been reduced to four (13%), and three
      children (11%) with appendicitis would have been discharged. CONCLUSION: The use
      of a predictive mathematical model may facilitate the diagnosis of appendicitis
      to avoid unnecessary operations.

PMID- 15723234
TI  - Effectiveness of a new carrier-bound fibrin sealant versus argon beamer as
      haemostatic agent during liver resection: a randomised prospective trial.
AB  - BACKGROUND AND AIMS: A new carrier-bound fibrin sealant, TachoSil, is expected to
      be efficacious and safe as a haemostatic treatment in hepatic resection. DESIGN:
      A prospective, randomised, open and controlled multicentre trial with
      intraoperative as well as postoperative assessment of efficacy and a 1 month
      follow-up period. SETTING: Tertiary care centres. PATIENTS/METHODS: One hundred
      and twenty-one patients requiring secondary haemostasis during planned liver
      resection. Patients with coagulation disorders and patients with persistent major
      bleeding after primary haemostatic measures were excluded. INTERVENTION:
      Application of either carrier-bound fibrin sealant (n=59) or argon beamer (argon
      beam coagulator) (n=62) as secondary haemostatic treatment. MAIN OUTCOME MEASURE:
      Time to intraoperative haemostasis. RESULTS: There was a significant superiority
      of TachoSil over argon beamer with regard to time to haemostasis (3.9 min, median
      3.0, range 3-20 min vs 6.3 min, median 4.0, range 3-39 min) (P=0.0007).
      Haemoglobin concentration of drainage fluid was significantly lower on day 2
      after surgery in TachoSil patients (1.1 mmol/l) than in argon beamer patients
      (2.3 mmol/l) (P=0.012). Overall, the frequency and causality of adverse events
      did not differ between the two treatment groups. CONCLUSION: TachoSil is superior
      to argon beamer in obtaining effective and fast intraoperative haemostasis. The
      safety data show TachoSil to be tolerable and safe for haemostatic treatment in
      liver resection.

PMID- 15723235
TI  - Can plants use an entomopathogenic virus as a defense against herbivores?
AB  - It is by now well established that plants use various strategies to defend
      themselves against herbivores. Besides conventional weapons such as spines and
      stinging hairs and sophisticated chemical defenses, plants can also involve the
      enemies of the herbivores in their defense. It has been suggested that plants
      could even use entomopathogens as part of their defense strategies. In this
      paper, we show that Brassica oleraceae plants that are attacked by Myzus persicae
      aphids infected with an entomopathogenic parvovirus (M. persicae densovirus)
      transport the virus through the phloem locally and systematically. Moreover,
      healthy aphids that fed on the same leaf, but separated from infected aphids were
      infected via the plant. Hence, this is proof of the principle that plants can be
      vectors of an insect virus and can possibly use this virus as a defense against
      herbivores.

PMID- 15723237
TI  - Norleucine, a natural occurrence in a novel ergot alkaloid gamma-ergokryptinine.
AB  - A novel natural peptide ergot alkaloid gamma-ergokryptinine containing norleucine
      has been isolated from ergot sclerotia of the field-growing parasitic fungus
      Claviceps purpurea CCM 8059. Its structure was deduced from the NMR and mass
      spectral data. The final structural proof was provided by the crystal structure
      determination, which is the first X-ray structure of a natural Nle-containing
      secondary metabolite. The conformations of three ergopeptinines: gamma
      ergokryptinine, ergoladinine, and alpha-ergokryptinine were compared.

PMID- 15723236
TI  - Redistribution of the water channel protein aquaporin-4 and the K+ channel
      protein Kir4.1 differs in low- and high-grade human brain tumors.
AB  - The blood-brain barrier (BBB) regulation is characterized by an interplay between
      endothelial cells, subendothelial basal laminae and astrocytic cells. Astroglial
      cells are highly polarized by the differentiation of perivascular membrane
      domains. These domains are characterized by the aggregation of, among other
      molecules, the water channel protein aquaporin-4 (AQP4), the dystrophin
      dystroglycan complex, and the inwardly rectifying potassium channel protein
      Kir4.1. Normally, this ion channel plays an important role in spatial buffering
      of extracellular K(+) in the central nervous system, which only can be performed
      due to the non-uniform distribution of Kir4.1 across the surface of the glial
      cell. In this study, we observed a mislocalization of Kir4.1 in various human
      brain tumors (low- and high-grade astrocytomas and oligodendrogliomas),
      suggesting that buffering capacity of glial cells may be compromised, leading to
      water influx (cytotoxic edema). Interestingly, whereas dystrophin remained
      regularly restricted at the endfeet membranes in all cases investigated, AQP4 was
      found to be redistributed only in high-grade astrocytomas, not in low-grade
      astrocytomas. If the mechanisms of redistribution of AQP4 and Kir4.1 are
      different in low- and high-grade gliomas, this may suggest that the mechanisms of
      clustering of AQP4 and Kir4.1 at the glial endfeet membrane domains are also
      different. The redistribution of AQP4 in glioblastoma cells is discussed as a
      reaction to the vasogenic edema, as induced by the breakdown of the BBB, to
      facilitate reabsorption of excess fluid.

PMID- 15723238
TI  - Molecular imaging system for possible prediction of active retinopathy in
      patients with Diabetes mellitus.
AB  - OBJECTIVE: The deposition of advanced glycation end products is enhanced in
      Diabetes mellitus (DM) and has been linked to diabetic complications such as a
      microvascular disease. Glycated proteins have receptors on mononuclear blood
      cells (MBCs) and have been shown to generate reactive oxygen species altering
      gene expression and modifying cellular targets, such as endothelial cells.
      Retinal angiopathy is a frequently observed microvascular complication in DM
      patients. Because of the central role of activated MBCs, we hypothesised a
      functional link between specific alterations in gene expression of MBCs, an
      increased activity of matrix proteases in serum, and the extent of retinal
      angiopathy in DM. MATERIAL AND METHODS: An appearance and proliferation index of
      diabetic retinopathy was evaluated in 38 DM-patients using fluorescein
      angiography. Alterations of gene transcription levels in MBCs were investigated
      using hybridisation of individual mRNA-pools to Atlas Array with a concomitant
      quantification of specific cDNAs by "Real-Time"-PCR. The activity of matrix
      metalloproteinases MMP-2 and MMP-9 in individual serum samples was measured by
      zymography combined with densitometric imaging system. RESULTS AND CONCLUSIONS:
      Hybridisation to Atlas Array of mRNA-pools isolated from MBCs revealed an
      enhanced expression of recoverin in DM-patients compared to the control group.
      "Real-Time"-PCR showed the highest recoverin levels in the DM-subgroup with a
      high proliferation index. MMP-2 activity was highly increased in 36% of all
      patients, and in 44, 44, and 19% of patients with proliferative retinopathy,
      advanced proliferative retinopathy, and no detectable proliferation respectively.
      In those 3 groups MMP-9 activity was highly increased in 56, 67, and 31% of
      patients respectively, and in 44% of all DM-patients. In contrast to patients
      with active proliferation, the simultaneous high activation of all three genes
      was not observed in patients without active proliferation. The ex vivo molecular
      imaging system developed in this work may be helpful for the prediction of active
      proliferative retinopathy in DM.

PMID- 15723239
TI  - Combined analysis of biochemical parameters in serum and differential gene
      expression in circulating leukocytes may serve as an ex vivo monitoring system to
      estimate risk factors for complications in Diabetes mellitus.
AB  - OBJECTIVE: Oxidative stress plays a crucial role in the development of
      complications in Diabetes mellitus (DM). Individual sensitivity against stress,
      however, varies among DM-patients and results, therefore, in differential
      severity of consequent complications. To allow more complex interpretation of a
      delicate antioxidant/free radicals balance and its effect on cellular functions
      in individual DM-patients, we analysed a correlation between total antioxidant
      status (TAS), antioxidant gap (AtxGap), level of free radicals (FR), routine
      clinical biochemical parameters in blood and differential gene expression in
      circulating leukocytes of DM-patients versus non-diabetic individuals. RESULTS
      AND CONCLUSIONS: Positive correlation was found between TAS and creatinine
      (p=0.05), AtxGap and iron (p=0.025), and between AtxGap and anti-streptolysin O
      (p=0.025). Whereas no correlation was found between FR and any of the routine
      clinical parameters tested, a negative correlation was observed between AtxGap
      and glucose content (p=0.025) and between AtxGap and gamma-glutamyltransferase
      (p=0.05). An increased content of FR was shown to influence significantly an
      expression of selected stress responsible genes in leukocytes. Transcription
      levels of NF-kappaB, XRCC1 and 90-kDa heat-shock protein A were increased in all
      DM-patients compared to non-diabetic individuals. In contrast, an expression of
      XIAP and cytochrome P450 reductase was up-regulated in patients with decreased
      levels of both FR and TAS and increased body mass index. This differential
      expression of the stress responsible genes might be further considered as a
      potential risk factor for diverse DM-complications helping also in reliable
      monitoring of supplemental antioxidant therapy and more complex interpretation of
      delicate antioxidant/free radicals balance.

PMID- 15723240
TI  - Expression of ABC-1 transporter is elevated in human glioma cells under
      irradiation and temozolomide treatment.
AB  - OBJECTIVE: Chemo-therapeutic treatment of glioma patients has minor success.
      Little is known about mechanisms of a pronounced resistance of gliomas towards
      actual therapies, yet. ABC-1 belongs to the group of transporters known to be
      involved in the export of hydrophobic substances and vascular regulation. This
      study investigates an effect of both temozolomide (TMZ) treatment and/or
      irradiation on the expression of the ABC-1 transporter in human U87-MG glioma
      cells. MATERIAL AND METHODS: In parallel experiments U87-MG cells underwent
      either irradiation (RT), chemo-treatment (CT) using TMZ, and combined
      chemo/radiation-treatment (CT/RT). After each treatment the cells were incubated
      either 2 or 24 hours at 37 degrees C and counted before protein analysis using
      Western-Blot technique. RESULTS AND CONCLUSIONS: An exponential growth of
      cellular density was observed for both untreated and irradiated cells being,
      however, about 2-times slower in irradiated compared to untreated cells. In
      contrast the density increase of chemo-treated cells as well as that of cells,
      which underwent the combined CT/RT treatment was of linear nature. ABC-1
      expression was detected in untreated as well as treated cells. Increasing cell
      density and all kinds of treatment resulted in a considerably enhanced ABC-1
      expression. CT treatment resulted in highly up-regulated ABC-1 expression
      especially in non-confluent cultures compared to untreated cells. Irradiation had
      a comparable or even higher inducible effect on the ABC-1 expression rates
      depending, however, on cell density. The highest expression rates were observed
      in cultures with high cellular density 2 hours after application of the combined
      treatment. Strong up-regulation of ABC-1 expression under both irradiation and
      chemo-treatment might be a clue to multidrug and irradiation cross-resistance
      mechanisms of malignant glioma cells converting the ABC-1 transporter into an
      attractive pharmacological target for a clinical breakthrough in the therapy of
      malignant gliomas.

PMID- 15723241
TI  - An enhanced expression of ABC 1 transporter in circulating leukocytes as a
      potential molecular marker for the diagnostics of glaucoma.
AB  - OBJECTIVE: Glaucoma is a neurodegenerative disease. Since vascular dysregulation
      is supposed to be a risk factor for the development of glaucomatous damage, the
      preventive treatment might slow down the disease development. The efficiency of
      the therapeutic treatment depends particularly on a drug efflux pump regulated by
      ABC transporters. ABC 1 is also known to participate on the vascular regulation.
      This study was focused on the comparative analysis of ABC 1 expression levels in
      circulating leukocytes of non-glaucomatous individuals and glaucoma patients.
      RESULTS AND CONCLUSIONS: The expression rates of ABC 1 were significantly
      increased in leukocytes of glaucoma patients compared to non-glaucomatous
      individuals. The expression level of ABC 1 was, furthermore, highly homogeneous
      in glaucoma patients. In contrast, these expression levels in non-glaucomatous
      individuals were extremely heterogeneous. This transporter acts as the energy
      dependent unidirectional transmembrane cholesterol efflux pump and can export a
      wide range of hydrophobic drugs. Additionally an observed enhanced ABC 1
      expression in circulating leukocytes may be implicated in the vascular regulation
      mechanisms of glaucoma. We proposed the enhanced expression of ABC 1 in
      leukocytes as a potential marker for the diagnostics and ex vivo molecular
      monitoring of glaucoma.

PMID- 15723242
TI  - Increased DNA breaks and up-regulation of both G(1) and G(2) checkpoint genes
      p21(WAF1/CIP1) and 14-3-3 sigma in circulating leukocytes of glaucoma patients
      and vasospastic individuals.
AB  - OBJECTIVE: Vascular disorder leading to local ischemia/reperfusion has been shown
      to play an important role in the glaucomatous damage. A decreased expression
      level of XPGC-gene has been found in circulating leukocytes of normal-tension
      glaucoma patients. Although decreased activity of XPGC-gene leads to insufficient
      DNA-repair, no leukopenia has been observed in glaucoma. Molecular mechanisms
      ensuring cell survival have not been elucidated yet for glaucoma with vascular
      disorder. MATERIAL AND METHODS: Using the ex vivo optical imaging method of
      alkaline "comet assay" comparative quantification of DNA breaks was performed in
      circulating leukocytes of non-glaucomatous non-vasospastic and vasospastic
      individuals as well as both normal-tension and high-tension glaucoma patients.
      Relative expression levels of the anti-apoptotic factors P21(WAF1/CIP1) and 14-3
      3 sigma were investigated in all groups tested. RESULTS AND CONCLUSIONS: The
      quantification of P21(WAF1/CIP1) showed the highest expression rates in high
      tension glaucoma patients which were significantly higher than those in all other
      groups tested. The highest expression rates of 14-3-3 sigma were found in both
      groups of glaucoma patients. These expression levels correlated well with DNA
      breaks measured. Since the expression of P21(WAF1/CIP1) in leukocytes was shown
      to be crucial for their survival under stress conditions, we suppose further that
      the up-regulation of this gene is the key event in the survival mechanisms of
      leukocytes in glaucoma accompanied with vascular disorder. The p21(WAF1/CIP1)
      gene should be further taken into consideration as a potential marker, the up
      regulation of which in circulating leukocytes of vasospastic individuals may
      indicate an increased risk for the developing glaucoma.

PMID- 15723243
TI  - Effects of perinatal asphyxia on cell survival, neuronal phenotype and neurite
      growth evaluated with organotypic triple cultures.
AB  - The effect of perinatal asphyxia on brain development was studied with
      organotypic cultures from substantia nigra, neostriatum and neocortex. Asphyxia
      was induced by immersing foetuses-containing uterine horns removed from ready-to
      deliver rats into a water bath for 20 min. Following asphyxia, the pups were
      nursed by a surrogate dam and sacrificed after three days for preparing
      organotypic cultures. Non-asphyxiated caesarean-delivered pups were used as
      controls. Morphological features and cell viability were recorded during in vitro
      development. At day in vitro (DIV) 24, the cultures were treated for
      immunocytochemistry using antibodies against the N-methyl-D-aspartate receptor
      subunit 1 (NR1) and tyrosine hydroxylase (TH). While in vitro survival was
      similar in cultures from both asphyxiated and control animals, differences were
      observed when the neuronal phenotype was assessed. Compared to controls, the
      total number of NR1-positive neurons in substantia nigra, as well as the number
      of secondary to higher level branching of TH-positive neurites from asphyxiated
      pups were decreased, illustrating the vulnerability of the dopaminergic systems
      to perinatal asphyxia.

PMID- 15723244
TI  - The effect of different mineral frames on ectopic bone formation in mouse hind
      leg muscles induced by native reindeer bone morphogenetic protein.
AB  - INTRODUCTION: Bone morphogenetic proteins (BMPs) require carrier material for
      slow release and framing material for osteoconduction. MATERIALS AND METHODS: The
      effect of a frame on early bone formation induced by partially purified native
      reindeer BMP in composite implants containing 3 mg of BMP, type IV collagen and
      tricalcium phosphate (TCP/Col/BMP) or hydroxyapatite (HA/Col/BMP) or biphasic
      tricalcium phosphate-hydroxyapatite (TCP/HA/Col/BMP) or biocoral (NC/Col/BMP) was
      evaluated using a mouse hind leg muscle pouch model. Collagen with native
      reindeer BMP (Col/BMP) and corresponding implants without native reindeer BMP
      served as controls. Evaluation was done by incorporation of 45Ca,
      radiographically and histologically 3 weeks after the implantation. RESULTS: None
      of the implants without native reindeer BMP were able to induce new bone visible
      on radiographs. The area of new bone formation in the Col/BMP (p=0.026) and
      TCP/HA/Col/BMP (p=0.012) groups was significantly greater than in the TCP/Col/BMP
      group. The optical density of the new bone area was significantly greater in the
      TCP/HA/Col/BMP group than in the TCP/Col/BMP (p=0.036) or Col/BMP (p=0.02)
      groups. 45Ca incorporation was many times greater in all the groups containing
      native reindeer BMP than in the corresponding groups without BMP. In the Col/BMP
      (p=0.046) and TCP/HA/Col/BMP (p=0.046) groups, 45Ca incorporation was
      significantly greater than in the TCP/Col/BMP group. No significant differences
      were found in any parameters between HA/Col/BMP and NC/Col/BMP groups and the
      other BMP-containing groups. CONCLUSIONS: Hydroxyapatite, biocoral and biphasic
      tricalciumphosphate-hydroxyapatite are equally good as framing material for
      native reindeer BMP, while tricalciumphosphate is somewhat worse. Osteoinduction
      of native reindeer BMP works well with collagen alone.

PMID- 15723245
TI  - Modified extra rotator-cuff entry point in antegrade humeral nailing.
AB  - INTRODUCTION: We describe an extra-articular, extra-rotator cuff entry point for
      antegrade humeral nailing, which preserves the articular surface and rotator cuff
      integrity. MATERIAL AND METHODS: Thirty-two patients with humeral shaft fractures
      underwent antegrade intramedullary nailing using a modified insertion point
      located 1 cm below the crest of the greater tuberosity, in a region outside the
      articular surface and rotator cuff area. RESULTS: In all cases, nailing was done
      successfully, without any perforation of the humeral inner cortex by the nail.
      Extension of the fracture line to the distal metaphysis happened intraoperatively
      in one case of a distal diaphysis fracture. In the remainder of the patients,
      postoperative reduction of the fracture was successful, with no sign of an
      iatrogenic incident of fracture comminution. Excellent active shoulder function
      and full early functional recovery of the shoulder joint (to 16th week
      postoperatively) were established in 98% of the patients. All fractures were
      united in a mean period of 14 weeks. CONCLUSION: We suggest an extra-articular,
      extra-rotator cuff entry point for antegrade humeral nailing as a possible and
      safe technique with beneficial results for the shoulder's postoperative function.

PMID- 15723246
TI  - No local recurrence of enchondroma after curettage and plaster filling.
AB  - INTRODUCTION: The most common treatment of enchondromas is curettage (with or
      without adjuvant therapy) followed by cancellous bone grafting. To avoid donor
      site morbidity of the iliac crest, we applied plaster of Paris as a bone defect
      filler after curettage of enchondromas. MATERIALS AND METHODS: We treated 19
      enchondromas of the hand and foot in 19 patients (mean age 40 years, range 21-79
      years) with curettage and filling of the cavity with sterile plaster of Paris
      (calcium sulphate/phosphate) tablets. RESULTS: The diagnosis was histologically
      confirmed in all cases. After a mean follow-up of 53 months (range 15-139
      months), the mean functional Muskuloskeletal Tumor Society Score was 29.1 points
      (97%; range 28-30). There were no local recurrences although adjuvant therapy was
      not utilized. CONCLUSION: Plaster of Paris appears safe and effective as a bone
      filling substance after curettage of enchondroma.

PMID- 15723247
TI  - Factor V Leiden and the prothrombin 20210A gene mutation and osteonecrosis of the
      knee.
AB  - INTRODUCTION: The pathogenesis behind osteonecrosis of the knee is still unknown.
      Circulatory impairment of the bone secondary to thrombosis in the
      microcirculation has been suggested as a mechanism. The purpose of this study was
      to examine the association between osteonecrosis of the knee and abnormalities in
      the thrombotic pathway in the form of factor V Leiden and the prothrombin 20210A
      gene mutation. MATERIALS AND METHODS: Thirty-eight consecutive patients (13 men
      and 25 women) with osteonecrosis of the knee without a history of knee trauma or
      surgery to the knee were enrolled in this study. Assays for the detection of
      factor V Leiden and the prothrombin 20210A gene mutation were performed, and the
      results were compared with those from 282 healthy volunteers. RESULTS: Six
      patients were diagnosed with secondary osteonecrosis, four corticosteroid-induced
      and two alcohol-induced. In 32 patients, no aetiological factor was found, and
      these patients were diagnosed with primary osteonecrosis of the knee. Twelve
      patients had 14 gene mutations, 11 factor V Leiden and 3 prothrombin 20210A gene
      mutations. Factor V Leiden and the prothrombin 20210A gene mutation occurred
      significantly (p=0.006) more frequently in patients with osteonecrosis than in a
      population of 282 healthy volunteers (odds ratio 3.1, 95%CI 1.4-6.6). CONCLUSION:
      The results of this study suggest that coagulation abnormalities in the form of
      factor V Leiden and the prothrombin 20210A gene mutation might play a role in
      osteonecrosis of the knee.

PMID- 15723248
TI  - Endoprosthetic replacement of the humerus combined with trapezius and latissimus
      dorsi transfer: a report of three patients.
AB  - INTRODUCTION: To improve the functional outcome after proximal and/or total
      humerus replacement, we combined the surgical procedures described by Bateman and
      Gerber. MATERIALS AND METHODS: In three patients after wide tumor resection,
      endoprosthetic replacement with a modular tumor endoprosthesis (MUTARS System)
      was performed. In addition to a capsular and muscular reconstruction using the
      Trevira tube, a trapezius transfer onto the Trevira tube in combination with a
      latissimus dorsi transfer onto the Trevira tube was performed. The patients were
      immobilized for 6 weeks after surgery with an abductor cast. RESULTS: After a
      follow-up of 1 year, there was no significant improvement of the shoulder
      function in comparison with patients who did not undergo the combined muscle
      transfer (control group n=16: mean abduction 37.5 degrees ; mean anteversion 35.0
      degrees ; mean internal rotation 15.2 degrees ; mean external rotation 25.2
      degrees ). CONCLUSION: In our patients, the combination of the Gerber and the
      Bateman procedures did not improve the shoulder function in patients with
      proximal and/or total humerus replacements. Therefore, the functional results do
      not justify two separate approaches and a prolonged operation time.

PMID- 15723250
TI  - Cervical spine injuries associated with lateral mass and facet joint fractures:
      new classification and surgical treatment with pedicle screw fixation.
AB  - To clarify the injury pattern, initial spinal instability, degree of
      discoligamentous injuries in cervical lateral mass and facet joint fractures, we
      retrospectively analyzed radiological parameters and introduced a new
      classification for these injuries. Surgical treatment was performed with cervical
      pedicle screw fixation (CPS), and overall neurological and radiological outcome
      was evaluated with a minimum follow-up period of 2 years. Lateral mass fractures
      were divided into the following four subtypes: separation, comminution, split,
      and traumatic spondylolysis. The sagittal and frontal alignments were evaluated
      at both mainly injured and adjacent spinal segments on radiographs. The initial
      discoligamentous injuries were investigated on magnetic resonance imaging in
      terms of their frequencies, subtype of injuries, and involved spinal levels.
      Anterior translation of fractured vertebra was demonstrated in 77% of lateral
      mass fractures, while 24% of anterior translation was observed, even in cephalad
      adjacent vertebrae. On magnetic resonance imaging, signal changes in anterior
      longitudinal ligament (ALL) and intervertebral disc were demonstrated in 76% of
      caudal segments and 24% of cephalad segments adjacent to fractured vertebra of
      lateral mass fractures. The subtype analyses of lateral mass fractures
      demonstrated high rates of anterior translation in separation, split, and
      traumatic spondylolisthesis, as well as significant coronal malalignment in
      comminution and split types (p<0.05). Thirty-one patients underwent surgical
      treatments using a cervical pedicle screw fixation. The CPS provided the superior
      capability of deformity correction without pseudoarthrosis, as well as excellent
      neurological recovery. The average numbers of stabilized segments were minimized
      without serious complications. In separation, facet joint fracture, and fractures
      with mild lateral mass comminution, the single level posterior fixation can be
      considered. The significant unstable injuries of split and comminution type with
      coronal malalignment can be treated with exclusive two-level posterior
      stabilization with CPS. The initial evaluation of fracture subtypes helps to
      successfully minimize the stabilized spinal segment.

PMID- 15723249
TI  - Correlation of radiographic and MRI parameters to morphological and biochemical
      assessment of intervertebral disc degeneration.
AB  - Degenerative disc disease (DDD) is a common finding in MRI scans and X-rays.
      However, their correlation to morphological and biochemical changes is not well
      established. In this study, radiological and MRI parameters of DDD were assessed
      and compared with morphological and biochemical findings of disc degeneration.
      Thirty-nine human lumbar discs (L1-S1), age 19-86 years, were harvested from
      eight cadavers. Within 48 h postmortem, MRIs in various spin-echo sequences and
      biplanar radiographs of intact spines were obtained. Individual discs with
      endplates were then sectioned in the mid-sagittal plane and graded according to
      the morphological appearance. Samples from the nucleus of each disc were
      harvested for biochemical analysis including water and proteoglycan contents. On
      MRIs, T2-signal intensity, Modic changes, disc extension beyond the interspace
      (DEBIT), nucleus pulposus shape, annular tears, osteophytes and endplate
      integrity were graded. On radiographs, an independent observer classified the
      parameters disc height, endplate sclerosis, osteophytes, Schmorl's nodes,
      intradiscal calcifications and endplate shape. General linear-regression models
      were used for statistical analysis. Backward elimination with a 10% significance
      cut-off level was used to identify the most significant parameters, which then
      were summed to create composite scores for radiography, MRI and the combination
      of both methods. The grading was performed by three observers, and a reliability
      analysis using Cronbach's alpha model was used to control interobserver
      agreement. The three radiographic parameters height-loss, osteophytes and
      intradiscal calcifications correlated significantly with the morphological degree
      of degeneration (p<0.001, R2=642). Significant differences of even one
      morphological grade could also be differentiated in the composite radiological
      score (p<0.05), except at the extremes between grades 1 and 2 and grades 4 and 5.
      All MRI parameters correlated significantly with the morphological grade
      (p<0.05); however Modic changes, T2-intensity and osteophytes accounted for 83%
      of the variation in the data. T2-signal intensity correlated significantly with
      H2O and proteoglycan content (p<0.001), and was best for detecting highly
      degenerated discs. Regression showed that the combined score was better
      correlated with the morphological grade (p<0.001, R2=775) than either the
      composite radiographic (p<0.001, R2=642) or composite MRI (p<0.001, R2=696)
      alone. Based on the combined score, a backwards elimination of the regression was
      performed, in which the parameters Modic changes, and T2-intensity loss (MRI) as
      well as calcifications (X-ray) accounted for 87% of the variability. The
      interobserver validation showed a high correlation for all three scores
      (Cronbach's alpha values ranging from 0.95 to 0.97). CONCLUSION: Selective
      imaging parameters and a newly created scoring scheme were found to correlate
      with disc degeneration as determined in a morphological manner. Surprisingly,
      radiographic parameters were able to distinguish different stages of
      degeneration, whereas MRI could only detect advanced stages of disc degeneration.
      We conclude that X-rays may remain a cost-effective, non-invasive in vivo-grading
      method to detect early disc degeneration, and, combined with MRI, correlate best
      with morphological and biochemical assessment of disc degeneration.

PMID- 15723251
TI  - CT evaluation of the pattern of odontoid fractures in the elderly--relationship
      to upper cervical spine osteoarthritis.
AB  - Odontoid fractures are common in the elderly following minor falls. Almost all of
      them have osteoarthritis of the cervical spine below the axis vertebra. As a
      result, there is increased stress on the spared upper cervical spine, resulting
      in a higher incidence of injuries. As movement in the upper cervical spine
      involves participation of five joints, degeneration in any one particular joint
      may affect the biomechanics of loading of the upper cervical spine. We aimed to
      analyse the relationship of odontoid fractures to the pattern of upper cervical
      spine osteoarthritis in the elderly. We studied the CT-scan images of the
      cervical spine in 23 patients who were over the age of 70 years and had odontoid
      fractures. In each patient, the type of odontoid fracture and the characteristics
      of the degenerative changes in each joint were analysed. Twenty-one of 23
      patients had Type-II odontoid fractures. The incidence of significant atlanto
      odontoid degeneration in these individuals was very high (90.48%), with relative
      sparing of the lateral atlantoaxial joints. Osteoporosis was found in 13 of 23
      patients at the dens-body junction and in seven of 23 patients at the odontoid
      process and body of the axis. With ageing, progressively more severe degenerative
      changes develop in the atlanto-odontoid joint. These eventually obliterate the
      joint space and fix the odontoid to the anterior arch of the atlas. In contrast,
      the lateral atlantoaxial joints are hardly affected by osteoarthritis. Thus,
      ultimately, atlantoaxial movements including atlantoaxial rotation are markedly
      limited by osteoarthritis of the atlanto-odontoid joint. However, there is still
      potential for movement in the lateral atlantoaxial joints, as they remain
      relatively free of degenerative change. The vulnerability of the atlantoaxial
      segment is further increased by markedly limited rotation below the axis vertebra
      due to severe facet-joint degeneration. As a consequence, a relatively low-energy
      trauma to the lateral part of the face, for instance by a fall, will induce
      forced atlantoaxial rotation. This, with the marked limitation of movement at the
      atlanto-odontoid joint, will produce a torque force at the base of the odontoid
      process leading to a Type II fracture.

PMID- 15723254
TI  - Variation in coding (NADH dehydrogenase subunits 2, 3, and 6) and noncoding
      intergenic spacer regions of the mitochondrial genome in Octocorallia (Cnidaria:
      Anthozoa).
AB  - Low rates of evolution in cnidarian mitochondrial genes such as COI and 16S rDNA
      have hindered molecular systematic studies in this important invertebrate group.
      We sequenced fragments of 3 mitochondrial protein-coding genes (NADH
      dehydrogenase subunits ND2, ND3 and ND6) as well as the COI-COII intergenic
      spacer, the longest noncoding region found in the octocoral mitochondrial genome,
      to determine if any of these regions contain levels of variation sufficient for
      reconstruction of phylogenetic relationships among genera of the anthozoan
      subclass Octocorallia. Within and between the soft coral families Alcyoniidae and
      Xeniidae, sequence divergence in the genes ND2 (539 bp), ND3 (102 bp), and ND6
      (444 bp) ranged from 0.5% to 12%, with the greatest pairwise distances between
      the 2 families. The COI-COII intergenic spacer varied in length from 106 to 122
      bp, and pairwise sequence divergence values ranged from 0% to 20.4%. Phylogenetic
      trees constructed using each region separately were poorly resolved. Better
      phylogenetic resolution was obtained in a combined analysis using all 3 protein
      coding regions (1085 bp total). Although relationships among some pairs of
      species and genera were well supported in the combined analysis, the base of the
      alcyoniid family tree remained an unresolved polytomy. We conclude that variation
      in the NADH subunit coding regions is adequate to resolve phylogenetic
      relationships among families and some genera of Octocorallia, but insufficient
      for most species - or population-level studies. Although the COI-COII intergenic
      spacer exhibits greater variability than the protein-coding regions and may
      contain useful species-specific markers, its short length limits its phylogenetic
      utility.

PMID- 15723255
TI  - Three-dimensional trabecular bone architecture of the lumbar spine in bone
      metastasis from prostate cancer: comparison with degenerative sclerosis.
AB  - OBJECTIVE: Prostate cancer frequently metastasizes to bone, inducing
      osteosclerotic lesions. The objective of this study was to clarify the three
      dimensional (3D) trabecular bone microstructure in bone metastasis from prostate
      cancer by comparison with normal and degenerative sclerotic bone lesions, using
      microcomputed tomography (micro-CT). DESIGN AND MATERIALS: A total of 32
      cancellous bone samples were excised from the lumbar spine of six autopsy
      patients: 15 metastatic samples (one patient), eight degenerative sclerotic
      samples (four patients) and the rest from normal sites (three patients). The
      samples were serially scanned cross-sectionally by micro-CT with a pixel size of
      23.20 microm, slice thickness of 18.56 microm, and image matrix of 512 x 512.
      Each image data set consisted of 250 consecutive slices. The volumes of interest
      (96 x 96 x 120 voxels) were defined in the original image sets and 3D indices of
      the trabecular microstructure were determined. RESULTS: The trabecular thickness
      (Tb.Th) in degenerative sclerotic lesions was significantly higher than that in
      normal sites, whereas no significant difference was observed in trabecular number
      (Tb.N). By contrast, in metastatic lesions, the Tb.N was significantly higher
      with increased bone volume fraction (BV/TV) than in normal sites, and no
      significant difference was found in Tb.Th. The characteristics of the trabecular
      surface in the metastatic samples showed concave structural elements with an
      increase in BV/TV, indicating osteolysis of the trabecular bone. In 3D
      reconstructed images, increased trabecular bone with an irregular surface was
      observed in samples from metastatic sites, which were uniformly sclerotic on soft
      X-ray radiographs. CONCLUSION: These results support, through 3D morphological
      features, the strong bone resorption effect in bone metastasis from prostate
      cancer.

PMID- 15723256
TI  - Phosphorylcholine-containing polymers for biomedical applications.

PMID- 15723257
TI  - Corrosion resistance and bioactivity of titanium after surface treatment by three
      different methods: ion implantation, alkaline treatment and anodic oxidation.
AB  - The paper compares the effects of various surface modifications, ion
      implantation, alkaline treatment and anodic oxidation, upon the corrosion
      resistance and bioactivity of titanium. The chemical composition of the surface
      layers thus produced was determined by XPS, SIMS and EDS coupled with SEM. The
      structure of the layers was examined by TEM, and their phase composition by XRD.
      The corrosion resistance was determined by electrochemical methods after the
      samples were exposed to the test conditions for 13 h. The bioactivity of titanium
      was evaluated in a simulated body fluid at a temperature of 37 degrees C after
      various exposure time.

PMID- 15723258
TI  - Patupilone (epothilone B, EPO906) and imatinib (STI571, Glivec) in combination
      display enhanced antitumour activity in vivo against experimental rat C6 glioma.
AB  - PURPOSE: The microtubule-stabilizing agent patupilone (epothilone B, EPO906) and
      the tyrosine kinase inhibitor imatinib (STI571, Glivec) which primarily inhibits
      Bcr-Abl, PDGF and c-Kit tyrosine kinase receptors, were combined in vivo to
      determine if any interaction would occur with respect to antitumour effect and
      tolerability using rat C6 glioma xenografted into nude mice. METHODS: Patupilone
      and imatinib were administered alone or in combination at suboptimal doses.
      Imatinib treatment (orally once daily) was initiated 4 days after s.c. injection
      of rat C6 glioma cells into athymic nude mice and patupilone administration (i.v.
      once per week) was started 3 or 4 days after imatinib treatment. RESULTS: As a
      single agent, imatinib was inactive in the regimens selected (100 mg/kg: T/C 86%
      and 116%; 200 mg/kg: T/C 68% and 84%; two independent experiments), but well
      tolerated (gain in body weight and no mortalities). Patupilone weekly monotherapy
      demonstrated dose-dependent antitumour effects (1 mg/kg: T/C 67% and 70%; 2
      mg/kg: T/C 32% and 63%; 4 mg/kg: T/C 3% and 46%). As expected, dose-dependent
      body weight losses occurred (final body weight changes at 1 mg/kg were -7% and 
      3%; at 2 mg/kg were -23% and -13%; and at 4 mg/kg were -33% and -15%). Combining
      2 mg/kg patupilone and 200 mg/kg per day imatinib in one experiment produced a
      non-statistically significant trend for an improved antitumour effect over
      patupilone alone (combination, T/C 9%), while in the second experiment,
      enhancement was seen with the combination and reached statistical significance
      versus patupilone alone (combination, T/C 22%; P=0.008). Reduction of the
      imatinib dose to 100 mg/kg per day resulted in no enhancement of antitumour
      activity in combination with 2 mg/kg patupilone. Reduction of the patupilone dose
      to 1 mg/kg resulted in a reduced antitumour effect, and only a trend for synergy
      with either imatinib dose (combination, T/C 46% and 40%). Pooling the data from
      the two experiments confirmed a significant synergy for the combination of 2
      mg/kg patupilone and 200 mg/kg per day imatinib (P=0.032), and a trend for
      synergy at the 1 mg/kg patupilone dose. Reduction in the imatinib dose to 100
      mg/kg per day resulted only in additivity with either dose of patupilone. Body
      weight losses were dominated by the effect of patupilone, since no greater body
      weight loss was observed in the combination groups. CONCLUSION: Combining
      patupilone with high-dose imatinib produced an increased antitumour effect
      without affecting the tolerability of treatment in a relatively chemoresistant
      rat C6 glioma model. Such results indicate that further evaluation is warranted,
      in particular to elucidate possible mechanisms of combined action.

PMID- 15723259
TI  - Role of glutathione and nucleotide excision repair in modulation of cisplatin
      activity with O6-benzylguanine.
AB  - PURPOSE: Modulation of platinating agent cytotoxicity has important clinical
      implications as a result of their widespread use in the treatment of many
      different cancers. O6-Benzylguanine (BG) enhances the cytotoxicity of cisplatin
      against several human tumor lines. The purpose of our work was to elucidate
      whether BG affects pathways prior to DNA damage (i.e., glutathione, GSH) or
      following DNA damage (i.e., nucleotide excision repair, NER). METHODS: In efforts
      to determine the mechanism of enhancement we: (1) evaluated whether different
      sequences of BG plus cisplatin treatment differed in their ability to enhance
      cisplatin-induced cytotoxicity and DNA platination; (2) determined the effect of
      BG on GSH and glutathione S-transferase (GST) activity and; (3) determined
      whether BG enhanced cisplatin-induced cytotoxicity in cells lacking specific
      enzymes in the NER pathway. Colony-forming assay, atomic absorption spectroscopy
      and HPLC were employed to measure tumor cell growth inhibition, quantitate the
      amount of platinum on DNA, and determine intracellular GSH concentrations,
      respectively. RESULTS: Increased cytotoxicity and platination of DNA was observed
      when cells were exposed to BG prior to and/or during cisplatin treatment and not
      when BG followed cisplatin treatment. BG did not significantly alter GST activity
      with minimal depletion of GSH. In contrast, buthionine sulfoximine (BSO) caused a
      much more dramatic decrease in GSH than BG that was not accompanied by a dramatic
      increase in sensitivity to cisplatin. Furthermore, BG enhanced the cytotoxicity
      of cisplatin in a series of cell lines deficient in NER. CONCLUSIONS: Overall,
      our results suggest that the mechanism of enhancement involves neither the GSH
      nor the NER pathways, but triggers an event prior to DNA platination damage that
      ultimately results in increased cytotoxicity, apoptosis and increased platination
      levels.

PMID- 15723260
TI  - Interactions of carboxypeptidase G2 with 6S-leucovorin and 6R-leucovorin in
      vitro: implications for the application in case of methotrexate intoxications.
AB  - Carboxypeptidase G2 (CPG2) is used when unexpected toxicity or renal failure
      occurs during high-dose methotrexate therapy. Leucovorin is also administered to
      antagonise the effects of methotrexate on purine anabolism. To investigate the
      effects of CPG2 on leucovorin rescue, we incubated the enzyme with both
      stereoisomers and analysed the degradation. A method for separating the
      stereoisomers of leucovorin, the internal standard aminopterin and the
      degradation products by capillary electrophoresis with 2.6-dimethyl-beta
      cyclodextrin as a chiral selector has been developed. The active 6S-leucovorin is
      degraded much faster than the inactive 6R-isomer. The maximum observed
      degradation velocity was 31 microM/min for 6S-leucovorin and 20 microM/min for 6R
      leucovorin, respectively, with an initial concentration of each stereoisomer of
      250 microM. Similar results were obtained at lower concentrations of leucovorin
      isomers. Thus, the selectivity of CPG2 for methotrexate in comparison to
      leucovorin is not as high as anticipated in the literature as only the active 6S
      leucovorin and not the mixture of the diastereomers should be taken into account.
      We conclude that the protective effects of leucovorin are antagonized by CPG2.
      Therefore, CPG2 should be administered to patients with caution.

PMID- 15723261
TI  - Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine
      in patients with advanced solid malignancies.
AB  - PURPOSE: Capecitabine in combination with docetaxel given every 3 weeks has shown
      a high degree of activity in a number of tumor types, but at the expense of
      significant toxicity. To improve the therapeutic index, we evaluated a weekly
      regimen of docetaxel in combination with capecitabine, and determined the maximum
      tolerated dose, toxicities and pharmacokinetics of this combination. PATIENTS AND
      METHODS: Patients with advanced solid malignancies were treated with docetaxel on
      days 1 and 8, and capecitabine, twice daily on days 1-14, of an every-21-day
      cycle. Pharmacokinetics of docetaxel were assessed on days 1 and 8 of the first
      cycle of chemotherapy. RESULTS: Enrolled in the study were 25 patients. The most
      frequent toxicities were asthenia, hand-foot syndrome and mucositis. Inability to
      deliver at least 75% of the planned doses of both drugs during the first two
      cycles of chemotherapy was noted at dose levels 2, 3 and 4. Dose level 1
      (docetaxel 30 mg/m2 and capecitabine 825 mg/m2 twice daily) is the recommended
      dose for phase II studies. Five patients experienced a partial response, and
      eight patients had stabilization of disease. Coadministration of capecitabine did
      not alter the pharmacokinetics of docetaxel. CONCLUSION: The regimen consisting
      of docetaxel 30 mg/m2 (days 1, 8) and capecitabine 825 mg/m2 twice daily (days 1
      14) was well tolerated. Capecitabine did not alter pharmacokinetics of docetaxel.
      Further testing of this regimen in tumor-specific trials, especially gastric,
      lung and breast cancer, is warranted.

PMID- 15723262
TI  - Biochemical modulation of cytarabine triphosphate by clofarabine.
AB  - PURPOSE: Clofarabine has proven to be effective in the treatment of adult and
      pediatric acute myelogenous leukemia (AML). To investigate if clofarabine could
      be used with success in biochemical modulation strategies, we investigated the
      biochemical modulation of cytarabine triphosphate (ara-CTP) by clofarabine in a
      myeloid leukemia cell line and the effect of this combination on cytotoxicity.
      EXPERIMENTAL DESIGN: K562 cells were incubated with clofarabine and ara-C either
      sequentially or simultaneously to evaluate the combination effect on their
      phosphorylated metabolites. Clonogenic assays were used to determine the
      cytotoxicity of each agent alone and in combination. Deoxynucleotide analysis was
      performed to assess the effect of clofarabine on dNTPs. RESULTS: Clofarabine
      added either simultaneously or in sequence increased ara-CTP accumulation. The
      maximal modulation of ara-CTP accumulation occurred with 1 microM clofarabine.
      This level was achieved at the maximum tolerated dose for adult and pediatric
      patients with AML. With 10 microM ara-C alone, 86 microM ara-CTP had accumulated
      after 3 h. The optimal sequence for the drug combination, i.e., clofarabine
      followed 4 h later by ara-C, resulted in 248 microM ara-CTP at 3 h. Clofarabine
      accumulated maximally in the monophosphate form. Preincubation with ara-C did not
      affect the triphosphate form, but it lowered clofarabine monophosphate.
      Clofarabine resulted in the intracellular decrease of dATP and dGTP levels.
      Clonogenic assays revealed that the combination of clofarabine and ara-C produced
      synergistic killing of myeloid leukemia cells. CONCLUSIONS: These findings
      demonstrate that combination of clofarabine followed by ara-C results in a
      biochemical modulation of ara-CTP and synergistic cell kill. These studies
      provide a compelling rationale for clinical trials using this combination regimen
      for adult and pediatric patients with AML.

PMID- 15723263
TI  - Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8
      production in gastric cancer cells.
AB  - The epidermal growth factor receptor (EGFR) and its ligands are involved in tumor
      growth, metastasis, angiogenesis, and resistance to chemotherapy. The findings
      reported here demonstrate that SN38 (the active metabolite of CPT-11) induces the
      tyrosine phosphorylation of EGFR within 5 min, followed by the induction of
      transcripts and/or proteins of the heparin-binding EGF-like growth factor,
      amphiregulin, transforming growth factor-alpha, and interlukin-8 (IL-8) in AGS
      gastric cancer cells. SN38 also activates nuclear factor-kappa B and activator
      protein-1, both of which are critical for the transcription of the IL-8 gene.
      However, the blocking of EGFR activation by gefitinib ("Iressa", ZD1839), an EGFR
      TKI (tyrosine kinase inhibitor), abrogates all the above reactions. The SN38
      triggered mechanisms include the generation of reactive oxygen species (ROS) and
      the activation of protein kinase C (PKC), followed by metalloproteinase
      activation and the sequential ectodomain shedding of EGFR ligands. These findings
      suggest that EGF signaling is enhanced by CPT-11 and point to the potential
      benefit of the use of a combination of CPT-11 with gefitinib in the treatment of
      certain gastric cancers.

PMID- 15723264
TI  - New ABCC6 gene mutations in German pseudoxanthoma elasticum patients.
AB  - Pseudoxanthoma elasticum (PXE; OMIM 177850 and 264800) is a rare heritable
      disorder of the connective tissue affecting the extracellular matrix of the skin,
      eyes, gastrointestinal system, and cardiovascular system. It has recently been
      found that mutations in the ABCC6 gene encoding the multidrug resistance
      associated protein (MRP) 6 cause PXE. This study examined novel mutations in the
      ABCC6 gene in our cohort of 76 German PXE patients and 54 unaffected or not yet
      affected relatives with a view to expanding the known mutational spectrum of the
      gene. Mutational analysis was performed using denaturing high-performance liquid
      chromatography and direct sequencing. The mutational screening revealed a total
      of 22 different ABCC6 sequence variations. We identified seven novel and four
      previously described PXE-associated mutations as well as eight novel neutral
      ABCC6 sequence variants. The new PXE-associated mutations included five missense
      mutations, one single base pair deletion, and one larger out-of-frame deletion.
      We suspect that the novel missense mutations lead to an impaired function of
      MRP6. Both deletions are predicted to result in a dysfunctional MRP6 protein. The
      seven new ABCC6 mutations were not present in 200 alleles from healthy blood
      donors which served as a control cohort. Most of the PXE patients who were found
      to carry PXE-causing ABCC6 mutations were assumed to manifest the PXE phenotype
      because of a compound heterozygous genotype. However, a genotype-phenotype
      correlation could not be established for the detected ABCC6 mutations. In
      summary, our data give a further insight into the spectrum of ABCC6 mutations in
      PXE patients.

PMID- 15723267
TI  - Impact of growth plate senescence on catch-up growth and epiphyseal fusion.
AB  - In mammals, longitudinal bone growth occurs rapidly in prenatal and early
      postnatal life, but then slows and eventually ceases. This deceleration, which
      reflects a decline in chondrocyte proliferation, was previously attributed to a
      hormonal or other systemic mechanism. However, new evidence suggests that it is
      due to a local mechanism within the growth plate. In particular, recent findings
      suggest that growth plate chondrocytes have a finite proliferative capacity that
      is gradually exhausted, causing growth to slow and finally stop. This concept has
      provided insight into clinical phenomena including catch-up growth after
      transient growth inhibition, catch-down growth after transient estrogen exposure,
      and epiphyseal fusion.

PMID- 15723265
TI  - Increased protein glycation in diabetes mellitus is associated with decreased
      aspirin-mediated protein acetylation and reduced sensitivity of blood platelets
      to aspirin.
AB  - Reduced effectiveness of the most common antiplatelet drug, acetylsalicylic acid
      (ASA, aspirin), in diabetes mellitus has been associated with a lowered platelet
      sensitivity to ASA and related to glycemic control in diabetic patients. Our
      objectives were (a) to monitor the chemical background of how chronic
      hyperglycemia affects platelet response to ASA in diabetes and (b) to study a
      chemical competition between the amount of bound acetyl residues and the extent
      of protein glycation in blood platelets. Using whole-blood impedance aggregometry
      and platelet function analyzer (PFA-100) we observed a reduced platelet response
      to ASA in diabetic patients (14% vs. 79% for PFA-100 collagen-epinephrine
      occlusion time) and an association between the index of glycemic control and
      platelet refractoriness to ASA (r(S) = -0.378). Impaired platelet response to ASA
      was related to enhanced platelet protein glycation (3.6+/-0.4 in diabetes vs.
      2.3+/-0.4 micromol fructosamine/microg protein in control) and reduced
      incorporation of acetyl residue into proteins of platelets from diabetic patients
      (47.4+/-2.0 in control vs. 33.1+/-0.7 micromol acetyl/microg protein in diabetic
      subjects). Incubation of blood platelets with increasing concentrations of
      glucose and ASA under in vitro conditions led to excessive modification in
      protein amino groups: glucose and ASA competed with each other in the course of
      nonenzymatic modifications, glycosylation, or acetylation, and their
      contributions to the occupancy of protein amino groups (R2 = 0.22 for glucose, R2
      = 0.43 for ASA) were dependent upon the concentrations of glucose and ASA.
      Overall the effects of high glucose and high ASA on the overall occupancy of
      protein free amino groups are not additive. While at higher concentrations ASA
      overcomes the effects of hyperglycemia and retards glycation, high glucose makes
      acetylation less efficient, and therefore the resultant chemical modification
      becomes greatly reduced. In conclusion, diminished susceptibility of various
      platelet proteins and receptors on blood platelet membranes to acetylation and
      high ambient glucose might underlie the apparently differentiated sensitivity of
      blood platelets to ASA and determine platelet "insensitivity to aspirin" in
      diabetic patients.

PMID- 15723269
TI  - Excretory/secretory products of sheep abomasal nematode parasites cause
      vacuolation and increased neutral red uptake by HeLa cells.
AB  - Excretory/secretory (ES) products of Ostertagia (Teladorsagia) circumcincta and
      Haemonchus contortus have been implicated in the inhibition of gastric acid
      secretion and vacuolation, and the loss of parietal cells associated with
      abomasal parasitism. Vacuolation of epithelial (HeLa) cells caused by adult O.
      circumcincta or L3 O. circumcincta or H. contortus ES products have been examined
      by differential interference contrast microscopy and by the neutral red uptake
      assay. ES products caused visible vacuolation of HeLa cells, and this effect was
      enhanced by 8 mM NH4Cl. Some parasite ES products caused a marked detachment of
      cells from the coverslip. At lower concentrations of ES products, neutral red
      uptake was usually increased above the control, but at higher concentrations of
      ES products, uptake was often decreased, probably because of cell detachment.
      Although generally consistent with direct observations of HeLa cell vacuolation
      by parasite chemicals, neutral red uptake was not a satisfactory quantitative
      assay.

PMID- 15723268
TI  - Rapid development of glomerular injury and renal failure in mice lacking p53R2.
AB  - The Rrm2b gene encodes p53R2, a catalytic subunit of ribonucleotide reductase
      that is required for DNA repair. Embryonic stem (ES) cells containing a
      retroviral insertion in the Rrm2b locus were used to generate mutant mice.
      Analysis of kidney RNA from Rrm2b (-/-) mice showed that the retroviral insertion
      disrupted expression of Rrm2b transcripts. Rrm2b (-/-) pups were represented at
      the expected Mendelian ratios at 10-12 days of age and grew normally past
      weaning. Mice failed to thrive after 6 weeks of age and began to die by 8 weeks
      of age. Phenotyping revealed that Rrm2b (-/-) mice died from a severe glomerular
      lesion that led to nephrotic syndrome and chronic renal failure. In kidneys of
      Rrm2b (-/-) mice, podocytes were enlarged and there was evidence of foot process
      effacement by 6 weeks of age. By 8 weeks of age, progressive podocyte hypertrophy
      and loss of foot processes was accompanied by hypertrophy of glomerular capillary
      endothelial cells that was extensive enough to restrict capillary blood flow.
      Collapsing glomerulopathy with avascular glomeruli was widespread in mice
      surviving beyond 9 weeks of age. Additional abnormalities in other organ systems
      were minor or consistent with secondary effects of renal failure. These findings
      suggest that lack of p53R2, the protein encoded by Rrm2b, has early and
      relatively selective detrimental effects on the kidney glomerulus that lead to
      rapid death from progressive renal failure.

PMID- 15723270
TI  - Schistosoma japonicum migration through mouse skin compared histologically and
      immunologically with S. mansoni.
AB  - The migration of Schistosoma japonicum and S. mansoni through mouse skin
      epidermis and dermis was compared by immunofluorescence techniques from 4 to 22 h
      after infection. At all times, the percentage of parasites detected in the dermis
      was significantly higher for S. japonicum than for S. mansoni. Thus, S. japonicum
      migrates more rapidly very early after infection. This agrees with the quicker
      migration observed previously by this species for later times. Both species
      expressed antigens related to the cercarial glycocalyx on the parasite body and
      antigenically detectable elastase in the acetabular glands, at least until 22 h
      after infection. Bot sets of antigens were also left as "traces" in cercarial
      migration channels in the skin as well as in skin tissue in the absence of
      detectable worms or migration channels. The data further substantiate differences
      between schistosome species in the speed of migration, and suggest that
      glycocalyx-related antigens and cercarial elastase continue to be expressed for
      at least 1 day after infection.

PMID- 15723271
TI  - Three-dimensional reconstruction of the distribution of flame cells in a
      trematode cercaria.
AB  - In order to reveal the vertical distribution of flame cells in a trematode
      cercaria, horizontal serial semi-thin sections were reconstructed by an image
      analyzer and a manual procedure. The ascending main excretory tubes extended
      forward, meandering up and down at the digestive system level from the excretory
      bladder. At the posterior end of the ventral sucker, they curved dorsally, passed
      through the dorsal side, returning to the mid level at the anterior end of the
      ventral sucker. They then ran forward to the posterior part of the oral sucker,
      and turned back. The flame cells were more abundant in the ventral region than in
      the dorsal region. The majority of pairs of right and left flame cells were
      present at the same distance from the digestive system or ventral (or dorsal)
      surface. This method, using conventional techniques, has some advantages for
      determining the horizontal and vertical distributions of flame cells in cercaria
      and may, therefore, promote research on cercaria.

PMID- 15723272
TI  - Chloroplast DNA microsatellite analysis supports a polyphyletic origin for
      barley.
AB  - Five barley chloroplast DNA microsatellites (cpSSRs) were used to study genetic
      relationships among a set of 186 barley accessions-34 Hordeum vulgare ssp.
      spontaneum (HS accessions) from Morocco, Ethiopia, Cyprus, Crete, Libya, Iraq,
      Iran, Turkey, Afghanistan and Israel, 122 H. vulgare ssp. vulgare landraces (HV
      landraces) from Spain, Bolivia (old Spanish introductions), Morocco, Libya and
      Ethiopia and 20 modern European spring barleys (HV cultivars). All loci were
      polymorphic in the material studied, with the number of alleles per locus ranging
      from two to three. Fifteen multi-locus haplotypes were observed, 11 in HS
      accessions and seven in HV landraces and cultivars. Of the seven haplotypes found
      in the HV lines, three were shared with the HS accessions, and four were unique.
      Cluster analysis revealed two main groups, one consisting of HS accessions from
      Ethiopia and the HV landraces from Spain, Bolivia (old Spanish), Morocco and
      Ethiopia, whereas the other larger group contained all of the other accessions
      studied. Based on these grouping and the existence of haplotypes found in the HV
      landraces and cultivars but not in the HS wild barley, a polyphyletic origin is
      proposed for barley, with further centres of origin in Ethiopia and the Western
      Mediterranean.

PMID- 15723273
TI  - Development of wheat near-isogenic lines for powdery mildew resistance.
AB  - Using three Chinese wheat cultivars, 'Bainong 3217', 'Beijing 837' and 'Laizhou
      953', as recurrent parents, 33 near-isogenic lines (NILs) carrying 22 powdery
      mildew resistance genes (Pm1c, Pm2, Pm4b, Pm12, Pm13, Pm16, Pm20, Pm21, Pm23, and
      13 undocumented genes) were developed. All NILs had no significant difference to
      their recurrent parents in the investigated traits of agronomic importance. The
      results of AFLP analysis indicated Jaccard's genetic similarity of the NILs with
      their recurrent parents varied from 0.96 to 0.98, and confirmed that the NILs had
      high genetic similarity with their recurrent parents. The resistance to powdery
      mildew was stably expressed by the relevant NILs. Eleven of the NILs were tested
      using molecular markers linked to the resistance genes Pm1c, Pm4b, Pm13, Pm21,
      PmP, PmE, PmPS5A, PmPS5B, PmY39, PmY150, and PmH, and they were all found to
      carry the targeted genes. The potential application of these NILs in gene
      discovery is discussed.

PMID- 15723274
TI  - Transfer of resistance to potato virus Y (PVY) from Nicotiana africana to
      Nicotiana tabacum: possible influence of tissue culture on the rate of
      introgression.
AB  - A disomic chromosome addition line of tobacco, Nicotiana tabacum L., was
      established previously that possesses a single chromosome pair from N. africana
      [Merxm. and Buttler]. This addition chromosome carries a gene that confers
      increased resistance to severe strains of potato virus Y (PVY). Methods to
      increase the probability of gene transfer from alien chromosomes to tobacco
      (2n=48) are desired. In the research described here, the PVY resistance gene was
      transferred to a tobacco chromosome from the N. africana addition chromosome in
      seven independent cases. One introgression event was obtained using conventional
      backcrossing of the disomic addition line to N. tabacum cv. Petite Havana, while
      the remaining six events were obtained using a scheme that involved exposure of
      explants of the addition line to tissue culture. Twenty-six derived 2n=48
      individuals heterozygous for PVY resistance were found to exhibit 24 bivalents or
      23 bivalents + 2 univalents at metaphase I. Ovular transmission rates for the PVY
      resistance factor ranged from 25% to 52%, while pollen transmission rates were
      much lower, ranging from 0 to 39%. Fifty-one random amplified polymorphic DNA
      (RAPD) markers specific for the intact addition chromosome were identified and
      used to characterize derived 2n=48/PVY-resistant genotypes. Variability was
      observed among these plants with respect to the total number of N. africana RAPD
      markers that were present, which is an indication that crossing over was
      occurring within each of the seven introgressed chromosome segments. A limited
      molecular marker-assisted backcrossing experiment allowed for selection of a
      2n=48/PVY-resistant individual that possessed only 6 of the 51 original N.
      africana RAPD markers. In vitro culture is potentially a valuable system for
      increasing the rate of alien gene transfer in tobacco, and the successful
      transfer of PVY resistance from N. africana may allow for an increased level and
      range of resistance to this virus in tobacco.

PMID- 15723275
TI  - Microsatellite-based high density linkage map in oil palm (Elaeis guineensis
      Jacq.).
AB  - A microsatellite-based high-density linkage map for oil palm (Elaeis guinensis
      Jacq.) was constructed from a cross between two heterozygous parents, a tenera
      palm from the La Me population (LM2T) and a dura palm from the Deli population
      (DA10D). A set of 390 simple sequence repeat (SSR) markers was developed in oil
      palm from microsatellite-enriched libraries and evaluated for polymorphism along
      with 21 coconut SSRs. A dense and genome-wide microsatellite framework as well as
      saturating amplified fragments length polymorphisms (AFLPs) allowed the
      construction of a linkage map consisting of 255 microsatellites, 688 AFLPs and
      the locus of the Sh gene, which controls the presence or absence of a shell in
      the oil palm fruit. An AFLP marker E-Agg/M-CAA132 was mapped at 4.7 cM from the
      Sh locus. The 944 genetic markers were distributed on 16 linkage groups (LGs) and
      covered 1,743 cM. Our linkage map is the first in oil palm to have 16 independent
      linkage groups corresponding to the plant's 16 homologous chromosome pairs. It is
      also the only high-density linkage map with as many microsatellite markers in an
      Arecaceae species and represents an important step towards quantitative trait
      loci analysis and physical mapping in the E. guineensis species.

PMID- 15723276
TI  - Flowering response of rice to photoperiod and temperature: a QTL analysis using a
      phenological model.
AB  - In this study we have attempted to quantify the thermal and photoperiodical
      responses of rice (Oryza sativa L.) flowering time QTLs jointly by a 'date-of
      planting' field experiment of a mapping population, and a 'phenological model'
      analysis that separately parameterizes the two responses, based on daily
      temperature, daily photoperiod and flowering date. For this purpose, the 'three
      stage Beta model', which parameterizes the sensitivity to temperature (parameter
      alpha), the sensitivity to photoperiod (parameter beta), and earliness under
      optimal conditions (10 h photoperiod at 30 degrees C) (parameter G), was applied
      to 'Nipponbare' x 'Kasalath' backcross inbred lines that were transplanted on
      five dates. QTLs for the beta value were detected in the four known flowering
      time QTL (Hd1, Hd2, Hd6 and Hd8) regions, while QTLs for the G value were
      detected only in the Hd1 and Hd2 regions. This result was consistent with
      previous reports on near-isogenic lines (NILs) of Hd1, Hd2 and Hd6, where these
      loci were involved in photoperiod sensitivity, and where Hd1 and Hd2 conferred
      altered flowering under both 10 and 14 h photoperiods, while Hd6 action was only
      affected by the 14 h photoperiod. Hd8 was shown to control photoperiod
      sensitivity for the first time. Interestingly, Hd1 and Hd2 were associated with a
      QTL for the alpha value, which might support the previous hypothesis that the
      process of photoinduction depends on temperature. These results demonstrate that
      our approach can effectively quantify environmental responses of flowering time
      QTLs without controlled environments or NILs.

PMID- 15723277
TI  - Over-expression of fibroblast growth factor-2 causes defective bone
      mineralization and osteopenia in transgenic mice.
AB  - Over-expression of human FGF-2 cDNA linked to the phosphoglycerate kinase
      promoter in transgenic (TgFGF2) mice resulted in a dwarf mouse with premature
      closure of the growth plate and shortening of bone length. This study was
      designed to further characterize bone structure and remodeling in these mice.
      Bones of 1-6 month-old wild (NTg) and TgFGF2 mice were studied. FGF-2 protein
      levels were higher in bones of TgFGF2 mice. Bone mineral density was
      significantly decreased as early as 1 month in femurs from TgFGF2 mice compared
      with NTg mice. Micro-CT of trabecular bone of the distal femurs from 6-month-old
      TgFGF2 mice revealed significant reduction in trabecular bone volume, trabecular
      number (Tb.N), and increased trabecular separation (Tb.Sp). Osteoblast
      surface/bone surface, double-labeled surface, mineral apposition rate, and bone
      formation rates were all significantly reduced in TgFGF2 mice. There were fewer
      TRAP positive osteoclasts in calvaria from TgFGF2 mice. Quantitative
      histomorphometry showed that total bone area was similar in both genotypes,
      however percent osteoclast surface, and osteoclast number/bone surface were
      significantly reduced in TgFGF2 mice. Increased replication of TgFGF2 calvarial
      osteoblasts was observed and primary cultures of bone marrow stromal cells from
      TgFGF2 expressed markers of mature osteoblasts but formed fewer mineralized
      nodules. The data presented indicate that non-targeted over-expression of FGF-2
      protein resulted in decreased endochondral and intramembranous bone formation.
      These results are consistent with FGF-2 functioning as a negative regulator of
      postnatal bone growth and remodeling in this animal model.

PMID- 15723278
TI  - Effect of low molecular weight heparin and different heparin molecular weight
      fractions on the activity of the matrix-degrading enzyme aggrecanase: structure
      function relationship.
AB  - The matrix-degrading enzyme aggrecanase has been identified in cartilage and is
      largely responsible for cartilage breakdown. The present study determined the
      efficacy of different heparin molecular weight fractions (HMWFs) and low
      molecular weight heparins (LMWHs) on aggrecanase activity. Aggrecanase activity
      was determined using biotinylated peptide substrate, which was immobilized onto
      streptavidin-coated 96-well plates; aggrecanase enzyme was then added.
      Proteolysis of the substrate at the specific amide bond was detected using
      specific antibody for the neoepitope generated. HMWFs ranging from 1,700 to
      12,000 Da demonstrated a concentration-dependent inhibitory efficacy of
      aggrecanase activity, with a Ki ranging from 5,000 nM down to 1 nM as a function
      of the molecular weight. The higher the molecular weight distribution, the
      greater the inhibitory efficacy of the heparin fragments toward aggrecanase
      activity. The absence or presence of antithrombin did not alter the affinity of
      heparin in inhibiting aggrecanase. Additionally, tissue factor pathway inhibitor
      at various levels did not alter the activity of aggrecanase. LMWHs demonstrated
      different levels of potency in inhibiting aggrecanase activity as a function of
      their average molecular weight distribution. Tinzaparin (average molecular weight
      = 6,500 Da) and enoxaparin (average molecular weight = 4,500 Da) demonstrated a
      Ki of 20 and 80 nM, respectively. The aggrecanase inhibitory effect of LMWH might
      contribute to blocking inflammation and tumor invasion by inhibiting aggrecanase
      activity and maintaining an intact extracellular matrix barrier.

PMID- 15723279
TI  - Effect of resveratrol on high glucose-induced stress in human leukemia K562
      cells.
AB  - Hyperglycemia, a symptom of diabetes mellitus, induces hyperosmotic responses,
      including apoptosis, in vascular endothelial cells and leukocytes. Hyperosmotic
      shock elicits a stress response in mammalian cells, often leading to apoptotic
      cell death. In a previous report, we showed that hyperosmotic shock induced
      apoptosis in various mammalian cells. Importantly, apoptotic biochemical changes
      (i.e., caspase-3 activation and DNA fragmentation) were blocked by antioxidant
      pretreatment during hyperosmotic shock-induced cell death. In the present study,
      we report that resveratrol, a phytoalexin present in grapes with known
      antioxidant and anti-inflammatory properties, attenuates high glucose-induced
      apoptotic changes, including c-Jun N-terminal kinase (JNK) activation and caspase
      3 activation in human leukemia K562 cells. Experiments with the cell permeable
      dye, 2',7'-dichlorofluorescein diacetate (DCF-DA), an indicator of reactive
      oxygen species (ROS) generation, revealed that high glucose treatment directly
      increased intracellular oxidative stress, which was attenuated by resveratrol. In
      addition, high glucose-treated K562 cells displayed a lower degree of attachment
      to collagen, the major component of vessel wall subendothelium. In contrast,
      cells pretreated with resveratrol followed by high glucose exhibited higher
      affinity for collagen. The results of this report collectively imply the
      involvement of oxidative stress in high glucose-induced apoptosis and alterations
      in attachment ability. Moreover, resveratrol blocks these events by virtue of its
      antioxidant property.

PMID- 15723280
TI  - N-cadherin mediated distribution of beta-catenin alters MAP kinase and BMP-2
      signaling on chondrogenesis-related gene expression.
AB  - We have examined the effect of calcium-dependent adhesion, mediated by N
      cadherin, on cell signaling during chondrogenesis of multipotential embryonic
      mouse C3H10T1/2 cells. The activity of chondrogenic genes, type II collagen,
      aggrecan, and Sox9 were examined in monolayer (non-chondrogenic), and micromass
      (chondrogenic) cultures of parental C3H10T1/2 cells and altered C3H10T1/2 cell
      lines that express a dominant negative form of N-cadherin (delta390-T1/2) or
      overexpress normal N-cadherin (MNCD2-T1/2). Our findings show that missexpression
      or inhibition of N-cadherin in C3H10T1/2 cells results in temporal and spatial
      changes in expression of the chondrogenic genes Sox9, aggrecan, and collagen type
      II. We have also analyzed activity of the serum response factor (SRF), a nuclear
      target of MAP kinase signaling implicated in chondrogenesis. In semi-confluent
      monolayer cultures (minimum cell-cell contact) of C3H10T1/2, MNCD2-T1/2, or
      delta390-T1/2 cells, there was no significant change in the pattern of MAP kinase
      or bone morphogenetic protein-2 (BMP-2) regulation of SRF. However, in micromass
      cultures, the effect of MAP kinase and BMP-2 on SRF activity was proportional to
      the nuclear localization of beta-catenin, a Wnt stabilized cytoplasmic factor
      that can associate with lymphoid enhancer-binding factor (LEF) to serve as a
      transcription factor. Our findings suggest that the extent of adherens junction
      formation mediated by N-cadherin can modulate the potential Wnt-induced nuclear
      activity of beta-catenin.

PMID- 15723282
TI  - Tuning the polymer release from hydrophilic matrix tablets by mixing short and
      long matrix polymers.
AB  - In this work a rotating disc method was developed for studying the dissolution
      process of "bimodal" polymer tablets, whose dissolution rates have been tuned by
      mixing low-molecular weight and high-molecular weight samples of poly(ethylene
      oxide) in various proportions. The tablets were prepared along different routes,
      by mixing the polymer fractions as powders or by mixing on a molecular level so
      that the effect of tablet heterogeneity could be assessed, but also by purifying
      the original powders so the effect of additives could be determined. When the
      mixed tablet was dominated by the low-molecular weight fraction, a faster
      dissolution was observed for the tablet mixed at the powder level. In those cases
      small gel pieces were released from the tablet during the whole dissolution
      process. As long as no gel piece erosion was observed, it did not matter if the
      two polymer fractions were blended on the molecular level or on the powder level,
      the steady-state dissolution rate was the same. The presence of small amounts of
      additives in the nonpurified commercial samples had no significant effect on the
      tablet dissolution within the uncertainty of the experiment.

PMID- 15723283
TI  - NGX6 gene inhibits cell proliferation and plays a negative role in EGFR pathway
      in nasopharyngeal carcinoma cells.
AB  - Nasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in
      other parts of the world. A novel NPC-related gene was isolated by location
      candidate cloning strategy, whose expression was down-regulated in NPC. This gene
      was designated human NGX6 (Genbank accession AF188239) and encoded a predicted
      protein of 338 amino acids that harbors an EGF-like domain. The effects of NGX6
      on cells from human NPC cell line HNE1 were investigated. The cells transfected
      with NGX6 had a markedly high expression of NGX6, leading to significant decrease
      in cell proliferation and the capability to form colonies in soft agar, delaying
      the G0-G1 cell cycle progression. Flow cytometry assay indicated that the
      expression of cyclin D1 significantly decreased in NGX6-transfected HNE1 cells as
      well as cyclin A and E. There was a delay in tumor formation and a dramatic
      reduction in tumor size when cells transfected with NGX6 were injected into nude
      mice. In another way, we found NGX6 played a negative role in EGFR Ras/Mek/MAPK
      pathway. We propose that NGX6, as an EGF-like domain gene, could delay cell cycle
      G0-G1 progression and thus inhibit cell proliferation by negatively regulating
      EGFR pathway in NPC cells and down-regulating the expression of cyclin D1 and E.

PMID- 15723284
TI  - Spatio-temporal organization of DNA replication in murine embryonic stem,
      primary, and immortalized cells.
AB  - The extent to which chromosomal domains are reorganized within the nucleus during
      differentiation is central to our understanding of how cells become committed to
      specific developmental lineages. Spatio-temporal patterns of DNA replication are
      a reflection of this organization. Here, we demonstrate that the temporal order
      and relative duration of these replication patterns during S-phase are similar in
      murine pluripotent embryonic stem (ES) cells, primary adult myoblasts, and an
      immortalized fibroblast line. The observed patterns were independent of fixation
      and denaturation techniques. Importantly, the same patterns were detected when
      fluorescent nucleotides were introduced into living cells, demonstrating their
      physiological relevance. These data suggest that heritable gene silencing during
      commitment to specific cell lineages is not mediated by global changes in the sub
      nuclear organization and replication timing of chromosome domains.

PMID- 15723285
TI  - Factors associated with preterm delivery in mothers of children with Beckwith
      Wiedemann syndrome: a case cohort study from the BWS registry.
AB  - Pregnancy that results in a child with Beckwith-Wiedemann syndrome (BWS) is
      associated with preterm delivery. Based on previous case series, we hypothesized
      that preterm delivery of a child with BWS was due to known risk factors for
      preterm delivery such as polyhydramnios and gestational hypertension. A case
      cohort study using the BWS Registry at Washington University School of Medicine
      was undertaken. Cases were pregnancies that resulted in the birth of a child with
      BWS, controls were pregnancies resulting in the birth of siblings without BWS.
      Univariate analyses of maternal complications and logistic regression to predict
      preterm delivery were used. Children with BWS (n = 304) were delivered preterm at
      a significantly higher rate than their siblings (n = 269) odds ratio 19.1 (95% CI
      9.1-40.2). Polyhydramnios, gestational hypertension, and vaginal bleeding also
      occurred at high rates in the BWS group with odds ratios of 31.6 (95% CI 12.6
      79.1), 2.4 (95% CI 1.4-4.1), and 3.9 (95% CI 2.3-6.4), respectively. In a
      multivariate logistic regression model within the BWS group, polyhydramnios,
      vaginal bleeding, and gestational hypertension were significant predictors of
      preterm delivery, odds ratios of 2.9 (95% CI 1.6-5.4), 2.6 (95% CI 1.3-5.0), and
      5.3 (2.3-12.0), respectively. However, a significant proportion, 6.5% (18 of
      277), of patients in the BWS group delivered preterm without known risk factors.
      Preterm delivery of a child with BWS is associated with an increased frequency of
      polyhydramnios, gestational hypertension, and vaginal bleeding in the mother.
      However, preterm delivery also occurs in the absence of these risk factors.

PMID- 15723286
TI  - Sexual dimorphism of growth plate prehypertrophic and hypertrophic chondrocytes
      in response to testosterone requires metabolism to dihydrotestosterone (DHT) by
      steroid 5-alpha reductase type 1.
AB  - Rat costochondral growth plate chondrocytes exhibit sex-specific and cell
      maturation dependent responses to testosterone. Only male cells respond to
      testosterone, although testosterone receptors are present in both male and female
      cells, suggesting other mechanisms are involved. We examined the hypothesis that
      the sex-specific response of rat costochondral cartilage cells to testosterone
      requires further metabolism of the hormone to dihydrotestosterone (DHT). Resting
      zone (RC) and growth zone (GC, prehypertrophic and upper hypertrophic zones)
      chondrocytes from male and female Sabra strain rats exhibited sex-specific
      responses to testosterone and DHT: only male cells were responsive. Testosterone
      and DHT treatment for 24 h caused a comparable dose-dependent increase in [3H]
      thymidine incorporation in quiescent preconfluent cultures of male GC cells, and
      a comparable increase in alkaline phosphatase specific activity in confluent
      cultures. RC cells responded in a differential manner to testosterone and DHT.
      Testosterone decreased DNA synthesis in male RC cells but DHT had no effect and
      alkaline phosphatase specific activity of male RC cells was unaffected by either
      hormone. Inhibition of steroid 5alpha-reductase activity with finasteride (1, 5,
      or 10 microg/ml), reduced the response of male GC cells to testosterone in a dose
      dependent manner, indicating that metabolism to DHT was required. RT-PCR showed
      that both male and female cells expressed mRNAs for steroid 5alpha-reductase type
      1 but lacked mRNAs for the type 2 form of the enzyme. Male cells also exhibited
      5alpha-reductase activity but activity of this enzyme was undetectable in female
      cells. These observations show that sex-specific responses of rat growth zone
      chondrocytes to testosterone requires the further metabolism of the hormone to
      DHT and that the effect of DHT in the male growth plate is maturation-state
      dependent. Failure of female chondrocytes to respond to testosterone may reflect
      differences in testosterone metabolism, since these cells possess greater ability
      to aromatize the hormone to estradiol.

PMID- 15723287
TI  - Diarsenic and tetraarsenic oxide inhibit cell cycle progression and bFGF- and
      VEGF-induced proliferation of human endothelial cells.
AB  - Arsenic trioxide (As2O3, diarsenic oxide) has recently been reported to induce
      apoptosis and inhibit the proliferation of various human cancer cells derived
      from solid tumors as well as hematopoietic malignancies. In this study, the in
      vitro effects of As2O3 and tetraasrsenic oxide (As4O6) on cell cycle regulation
      and basic fibroblast growth factor (bFGF)- or vascular endothelial growth factor
      (VEGF)-stimulated cell proliferation of human umbilical vein endothelial cells
      (HUVEC) were investigated. Significant dose-dependent inhibition of cell
      proliferation was observed when HUVEC were treated with either arsenical compound
      for 48 h, and flow cytometric analysis revealed that these two arsenical
      compounds induced cell cycle arrest at the G1 and G2/M phases--the increases in
      cell population at the G1 and G2/M phase were dominantly observed in As2O3- and
      As4O6-treated cells, respectively. In both arsenical compounds-treated cells, the
      protein levels of cyclin A and CDC25C were significantly reduced in a dose
      dependent manner, concomitant to the reduced activities of CDK2- and CDC2
      associated kinase. In G1-synchronized HUVEC, the arsenical compounds prevented
      the cell cycle progression from G1 to S phase, which was stimulated by bFGF or
      VEGF, through the inhibition of growth factor-dependent signaling. These results
      suggest that arsenical compounds inhibit the proliferation of HUVEC via G1 and
      G2/M phase arrest of the cell cycle. In addition, these inhibitory effects on
      bFGF- or VEGF-stimulated cell proliferation suggest antiangiogenic potential of
      these arsenical compounds.

PMID- 15723288
TI  - Is multicenter collaborative research in clinical genetics dead and, if so, what
      killed it?
AB  - This study describes the course of a clinical trial designed to investigate the
      possible role of thrombophilic factors in limb reduction defects, which was
      abandoned after 1 year because lack of progress of the project through ethics
      review and the failure to make significant inroads in patient recruitment.
      Factors that are thought to have contributed to the failure are discussed, in the
      hope that others can avoid some of the pitfalls.

PMID- 15723289
TI  - Genotypic and phenotypic characterization of Noonan syndrome: new data and review
      of the literature.
AB  - Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short
      stature, minor facial anomalies, and congenital heart defects. In approximately
      50% of cases the condition is caused by missense mutations in the PTPN11 gene on
      chromosome 12, resulting in a gain of function of the protein SHP-2. In this
      study, PTPN11 mutation analysis was performed in 170 NS patients. In 76 (45%) of
      them a mutation was identified. We report on the distribution of these mutations,
      as well as on genotype-phenotype relationships. The benefit of the NS scoring
      system developed by van der Burgt et al. [(1994); Am J Med Genet 53:187-191] is
      shown, among physicians who consequently based their diagnosis on the NS scoring
      system the percentage mutation positive subjects was 54%, whereas this percentage
      was only 39% among physicians who made less use of the scoring system. In two
      patients with some uncommon manifestations mutations were found in the C-SH2
      domain, a region in which defects are not often identified in NS. A trend was
      observed in patients carrying the 922A --> G change (Asn308Asp) receiving normal
      education. In one patient with NS and mild juvenile myelomonocytic leukemia
      (JMML) the mutation 218C --> T (Thr73Ile) was found. This confirms previous
      findings indicating that individuals with NS with specific mutations in PTPN11
      are at risk of developing JMML.

PMID- 15723290
TI  - Low frequency of BRAF and CDKN2A mutations in endometrial cancer.
AB  - Several pathways have been implicated in the pathogenesis of endometrial
      carcinoma. Based on recent reports, BRAF mutations provide an alternative route
      for activation of the RAS signalling pathway. The CDKN2A (p16) tumour suppressor
      gene is also altered in several tumour types. We therefore wanted to assess the
      pattern and prognostic impact of BRAF mutations and p16 alterations in
      endometrial carcinomas. Only 1 of 48 tumours (2%) was found to have a BRAF
      mutation in exon 15, whereas 8 of 45 tumours (18%) had a K-ras mutation.
      Homozygous deletion, amplification, promoter region methylation or mutation of
      the p16 gene was seen in 6 cases (13%), and 18 cases (38%) carried polymorphisms
      in the p16 gene. All tumours with presence of p16 methylation, non-sense
      mutation, deletion or amplification exhibited loss of p16 expression as evaluated
      by immunohistochemistry. Presence of a p16 hit was significantly correlated with
      high FIGO stage (p = 0.04), high histologic grade (p = 0.02), estrogen receptor
      negativity (p = 0.05), pathologic expression of p53 (p = 0.02), pathologic
      expression of p16 (p = 0.05) and poor survival (p = 0.02). There was also a
      significant correlation between loss of p16 expression and K-ras mutations,
      pathologic p53 expression and serous papillary/clear cell histologic types (p =
      0.05/p = 0.001/p = 0.002). In conclusion, BRAF mutation is an infrequent finding
      in endometrial carcinomas. Loss of p16 expression is seen in all cases with
      alterations of the p16 gene. The presence of a p16 hit might be important in a
      subset of endometrial carcinomas with aggressive clinical behaviour. However, the
      mechanism of p16 inactivation remains unclear for the majority of cases
      exhibiting loss of expression, but the interactions with K-ras and p53 should be
      further studied.

PMID- 15723291
TI  - Comparison of potential protective effects of melatonin, indole-3-propionic acid,
      and propylthiouracil against lipid peroxidation caused by potassium bromate in
      the thyroid gland.
AB  - Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid
      tumors. Melatonin and indole-3-propionic acid (IPA) are effective antioxidants.
      Some antioxidative effects of propylthiouracil (PTU)--a thyrostatic drug--have
      been found. The aim of the study was to compare protective effects of melatonin,
      IPA, and PTU against lipid peroxidation in the thyroids, collected from rats
      treated with KBrO3, and in homogenates of porcine thyroids, incubated in the
      presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on
      the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w.,
      i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for
      10 days). Homogenates of porcine thyroids were incubated for 30 min in the
      presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5,
      1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01,
      0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA
      + 4-HDA) was measured spectrophotometrically in thyroid homogenates. In vivo
      pretreatment with either melatonin or with IPA or with PTU decreased lipid
      peroxidation caused by KBrO3--injections in rat thyroid gland. Under in vitro
      conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced
      KBrO3-related lipid peroxidation in the homogenates of porcine thyroids. In
      conclusion, melatonin and IPA may be of great value as protective agents under
      conditions of exposure to KBrO3.

PMID- 15723293
TI  - Immunobiotherapy directed against mutated and aberrantly expressed gene products
      in pancreas cancer.
AB  - Genetic alterations are responsible for the development of cancer in ductal cells
      of the pancreas. These genetic changes result in abnormal molecular expression of
      proteins that are involved in cell proliferation, cell cycle control and
      adhesion. Some of the genetic mutations result in aberrant proteins that can be
      recognized as novel or foreign by cells of innate and adaptive immune systems.
      These are appropriate targets for therapeutic intervention which may involve
      immunobiologic approaches. These approaches may be less effective because of
      immune escape mechanisms developed by tumor cells within the microenvironment of
      the tumor mass. Immunobiotherapy intervention of pancreas cancer must circumvent
      these obstacles and integrate effective immunotherapy with molecularly targeted
      approaches to pancreas cancer intervention.

PMID- 15723292
TI  - Improved molecular diagnosis of dystrophinopathies in an unselected clinical
      cohort.
AB  - Mutations in the DMD gene result in Duchenne muscular dystrophy (DMD) and Becker
      muscular dystrophy (BMD). Readily available clinical tests detect only deletions
      of one exon or greater, which are found in approximately 60% of cases. Mutational
      analysis of other types of DMD mutations, such as premature stop codons and small
      frameshifting insertions or deletions, has historically been hampered by the
      large size of the gene. We have recently reported a method that allows the rapid
      and economical sequencing of the entire coding region of the DMD gene, and that
      is more sensitive than methods based on single-strand conformational polymorphism
      (SSCP) screening or other preliminary screening steps. Here we use single
      condition amplification/internal primer (SCAIP) sequencing analysis, in
      combination with multiplex amplifiable probe hybridization (MAPH) analysis of
      duplications, to report the frequency of mutations in a large cohort of
      unselected dystrophinopathy patients from a single clinic. Our results indicate
      that 7% of dystrophinopathy patients do not have coding region mutations,
      suggesting that intronic mutations are not uncommon. The availability of rapid
      and thorough mutation analysis from peripheral blood samples, along with an
      improved estimate of the percentage of non-coding region mutations, will be of
      benefit for improved genetic counseling and in identification of cohorts for
      clinical trials.

PMID- 15723294
TI  - Normal human osteoclasts formed from peripheral blood monocytes express PTH type
      1 receptors and are stimulated by PTH in the absence of osteoblasts.
AB  - The prevailing view for many years has been that osteoclasts do not express
      parathyroid hormone (PTH) receptors and that PTH's effects on osteoclasts are
      mediated indirectly via osteoblasts. However, several recent reports suggest that
      osteoclasts express PTH receptors. In this study, we tested the hypothesis that
      human osteoclasts formed in vitro express functional PTH type 1 receptors
      (PTH1R). Peripheral blood monocytes (PBMC) were cultured on bone slices or
      plastic culture dishes with human recombinant RANK ligand (RANKL) and recombinant
      human macrophage colony-stimulating factor (M-CSF) for 16-21 days. This resulted
      in a mixed population of mono- and multi-nucleated cells, all of which stained
      positively for the human calcitonin receptor. The cells actively resorbed bone,
      as assessed by release of C-terminal telopeptide of type I collagen and the
      formation of abundant resorption pits. We obtained evidence for the presence of
      PTH1R in these cells by four independent techniques. First, using
      immunocytochemistry, positive staining for PTH1R was observed in both mono- and
      multi-nucleated cells intimately associated with resorption cavities. Second,
      PTH1R protein expression was demonstrated by Western blot analysis. Third, the
      cells expressed PTH1R mRNA at 21 days and treatment with 10(-7) M hPTH (1-34)
      reduced PTH1R mRNA expression by 35%. Finally, bone resorption was reproducibly
      increased by two to threefold when PTH (1-34) was added to the cultures. These
      findings provide strong support for a direct stimulatory action of PTH on human
      osteoclasts mediated by PTH1R. This suggests a dual regulatory mechanism, whereby
      PTH acts both directly on osteoclasts and also, indirectly, via osteoblasts.

PMID- 15723295
TI  - Use of targeted array-based CGH for the clinical diagnosis of chromosomal
      imbalance: is less more?
AB  - Chromosome analysis is an important component to the diagnosis of congenital
      anomalies, developmental delay, and mental retardation. Routine chromosome
      analysis identifies aneuploidy and structural rearrangements greater than 5 Mb
      but cannot identify abnormalities of the telomeric regions or microdeletions
      reliably. Molecular cytogenetic techniques were developed to overcome these
      limitations. High-resolution comparative genomic hybridization (CGH)-based
      microarrays (array CGH) were developed to increase the resolution of chromosomal
      studies and to provide a comprehensive assay by using large-insert clones as the
      target for analysis. We constructed a microarray for the clinical diagnosis of
      medically significant and relatively common chromosomal alterations. Nine hundred
      six bacterial artificial chromosome (BAC) clones were chosen, the chromosomal
      locations of which were confirmed by fluorescence in situ hybridization (FISH).
      FISH-testing showed that 7% of the clones were mismapped based on map locations
      obtained from two publicly available databases (58 mapped to the wrong chromosome
      and three mapped to a different locus on the same chromosome), 16% cross
      hybridized to other chromosomes, and 12% did not hybridize or showed poor
      hybridization signals under uniform FISH conditions. Thus, from a total of 906
      BAC clones that were evaluated, only 589 (65%) were deemed adequate for arraying
      on this clinical device. The performance of this array was tested in a set of
      blinded experiments on a cohort of phenotypically normal individuals and on
      individuals with known chromosome abnormalities. The array identified
      deletion/duplication polymorphisms not seen by FISH in the phenotypically normal
      individuals and detected single copy dosage differences in all of the cases with
      known chromosomal abnormalities. All abnormalities detected by the array were
      confirmed by FISH with BACs from the appropriate loci. Our data demonstrate that
      the rigorous assessment of BACs and their use in array CGH is especially
      important when the microarray is used for clinical diagnosis. In addition, this
      study illustrates that when constructed carefully with proper attention to the
      quality of the BACs that are arrayed, array CGH is an effective and efficient
      tool for delineating chromosomal aberrations and an important adjunct to FISH and
      conventional cytogenetics.

PMID- 15723296
TI  - Contribution of Toll-like receptor/myeloid differentiation factor 88 signaling to
      murine liver regeneration.
AB  - Toll-like receptors (TLRs) act as innate immune signal sensors and play central
      roles in host defense. Myeloid differentiation factor (MyD) 88 is a common
      adaptor molecule required for signaling mediated by TLRs. When the receptors are
      activated, cells bearing TLRs produce various proinflammatory cytokines in a
      MyD88-dependent manner. Liver regeneration following partial hepatectomy (PH)
      requires innate immune responses, particularly interleukin-6 (IL-6) and tumor
      necrosis factor alpha (TNF-alpha) production by Kupffer cells, although the
      recognition and activation processes are still unknown. We investigated whether
      TLR/MyD88 signaling is critical for induction of innate immune responses after
      PH. In Myd88(-/-) mice after PH, induction of expression of immediate early genes
      involved in hepatocyte replication and phosphorylation of STAT3 in the liver, and
      production of TNF-alpha/IL-6 by and activation of NF-kappaB in the Kupffer cells
      were grossly subnormal and were associated with impaired liver regeneration.
      However, TLR2, 4 and 9, which recognize gram-negative and -positive bacterial
      products, are not essential for NF-kappaB activation and IL-6 production after
      PH, which excludes a possible contribution of TLR2/TLR4 or TLR9 to MyD88-mediated
      pathways. In conclusion, the TLR/MyD88 pathway is essential for incidental liver
      restoration, particularly its early phase.

PMID- 15723297
TI  - Lymphocyte traffic through sinusoidal endothelial cells is regulated by
      hepatocytes.
AB  - Crosstalk between hepatic sinusoidal ECs and closely juxtaposed hepatocytes via
      vascular endothelial growth factor is essential for the maintenance of sinusoidal
      endothelial growth and differentiation. We propose that paracrine interactions
      between endothelial cells and hepatocytes also may be responsible for the unique
      complement of adhesion receptors expressed on sinusoidal endothelium that
      regulate the recruitment of lymphocytes into the liver. To address this
      hypothesis, we developed an in vitro model of the hepatic sinusoid in which
      flowing lymphocytes could interact with hepatic endothelium conditioned by the
      presence of hepatocytes. Human hepatic sinusoidal endothelial cells cocultured
      with hepatocytes were activated so that they supported the adhesion of
      lymphocytes at levels equivalent to those seen on endothelium stimulated with the
      inflammatory cytokine tumour necrosis factor-beta. Lymphocyte adhesion was
      supported by intracellular adhesion molecule 1, vascular cell adhesion molecule
      1, and E-selectin, with an additional contribution from the novel adhesion
      receptor VAP-1. In conclusion, we show that interactions between hepatocytes and
      endothelial cells amplify leukocyte recruitment through the sinusoids by
      regulating the expression and function of endothelial adhesion molecules. These
      paracrine interactions may be responsible for the induction of the adhesion
      molecules that support constitutive lymphocyte recruitment to the liver as well
      as contributing significantly to the patterns of leukocyte adhesion seen during
      episodes of hepatic inflammation.

PMID- 15723298
TI  - Dietary and other risk factors in women having fibrocystic breast conditions with
      and without concurrent breast cancer: a nested case-control study in Shanghai,
      China.
AB  - Risk of breast cancer is increased in women with proliferative benign breast
      conditions. Most of these conditions, however, do not progress to breast cancer.
      The purpose of our study was to identify factors possibly associated with this
      progression. Women with proliferative fibrocystic breast conditions alone (214),
      and women with proliferative fibrocystic breast conditions and concurrent breast
      cancer (130), were compared to each other, and each of these groups of women were
      also compared to 1,070 controls; and 176 women with non-proliferative benign
      breast conditions alone, and 155 also with breast cancer, were similarly
      compared. All study subjects were selected from a cohort of women enrolled in a
      trial of breast self-examination in Shanghai. Women were interviewed to ascertain
      information on suspected risk factors for breast cancer and dietary habits.
      Conditional logistic regression was used to estimate adjusted odds ratios (OR)
      and 95% confidence intervals (CI). Increased risks of both proliferative
      fibrocystic breast conditions alone, and with breast cancer, were associated with
      low parity, a prior benign breast lump and breast cancer in a first-degree
      relative. Decreasing trends in the risk of both conditions with increasing intake
      of fruits and vegetables were observed. No factors were significantly associated
      with risk of breast cancer relative to risk of proliferative changes. Similar,
      but in some instances weaker, associations were observed for non-proliferative
      fibrocystic conditions with and without breast cancer. The possible risk or
      protective factors that were observed in our study most likely alter the risk of
      breast cancer at an early stage in the carcinogenic process, and probably do not
      alter risk of progression from proliferative fibrocystic breast conditions to
      breast cancer.

PMID- 15723299
TI  - Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour
      antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with
      DISC-mGM-CSF.
AB  - Direct intratumour injection of the disabled infectious single-cycle-herpes
      simplex virus-encoding murine granulocyte/macrophage colony-stimulating factor
      (DISC-HSV-mGM-CSF) into established colon carcinoma CT26 tumours induced complete
      tumour rejection in up to 70% of treated animals (regressors), while the
      remaining mice developed progressive tumours (progressors). This murine Balb/c
      model was used to dissect the cellular mechanisms involved in tumour regression
      or progression following immunotherapy. CTLs were generated by coculturing
      lymphocytes and parenchymal cells from the same spleens of individual regressor
      or progressor animals in the presence of the relevant AH-1 peptide derived from
      the gp70 tumour-associated antigens expressed by CT26 tumours. Tumour regression
      was correlated with potent CTL responses, spleen weight and cytokine (IFN-gamma)
      production. Conversely, progressor splenocytes exhibited weak to no CTL activity
      and poor IFN-gamma production, concomitant with the presence of a suppressor cell
      population in the progressor splenic parenchymal cell fraction. Further
      fractionation of this parenchymal subpopulation demonstrated that cells
      inhibitory to the activation of AH-1-specific CTLs, restimulated in vitro with
      peptide, were present in the nonadherent parenchymal fraction. In vitro depletion
      of progressor parenchymal CD3+/CD4+ T cells restored the CTL response of the
      cocultured splenocytes (regressor lymphocytes and progressor parenchymal cells)
      and decreased the production of IL-10, suggesting that CD3+CD4+ T lymphocytes
      present in the parenchymal fraction regulated the CTL response to AH-1. We
      examined the cellular responses associated with tumour rejection and progression,
      identifying regulatory pathways associated with failure to respond to
      immunotherapy.

PMID- 15723300
TI  - Mosaic tetrasomy 14pter-q13 due to a supernumerary isodicentric derivate of
      proximal chromosome 14q.
AB  - Tetrasomy of proximal 14q is an extremely rare condition and has never been
      reported to be associated with survival. We here report on the first case of
      mosaic tetrasomy of 14pter-q13 due to a de-novo supernumerary pseudoisodicentric
      chromosome in a 2-year-old boy with multiple dysmorphisms and malformations. The
      marker was detectable in nearly 25% of lymphocytes as well as in cells from
      buccal mucosa. Detailed fluorescence in situ hybridization (FISH) analyses
      allowed the characterization of the marker to entirely consist of proximal 14q
      material and to be symmetric. The pattern of clinical features in our patient
      only slightly correspond to that of patients with trisomy of proximal 14q, but
      further cases are needed to define whether tetrasomy of proximal 14q is a
      separate entity.

PMID- 15723301
TI  - Viral kinetics during antiviral therapy in patients with chronic hepatitis C and
      persistently normal ALT levels.

PMID- 15723303
TI  - Recombinant adeno-associated virus (rAAV) expressing TFPI-2 inhibits invasion,
      angiogenesis and tumor growth in a human glioblastoma cell line.
AB  - Recombinant adeno-associated viruses (rAAV) have become the vector of choice for
      many gene therapy protocols. rAAVs have a number of attractive features including
      long-term transgene expression and the ability to transduce both dividing and non
      dividing cells. We have shown previously the anti-cancer role of tissue factor
      pathway inhibitor-2 (TFPI-2), a matrix-associated serine protease inhibitor, in
      human glioblastomas. As a result of our present study, in which 0.8-kb fragment
      of human TFPI-2 was cloned into the adeno-associated viral vectors (rAAA-TFPI-2),
      rAAV-TFPI-2 infection of SNB19 cells significantly increased TFPI-2 as determined
      by Western blotting. As assessed by spheroid and Matrigel assays, infection of
      SNB19 cells with rAAV-TFPI-2 significantly reduced migration and invasion in a
      dose-dependent manner. Tumor spheroids infected with rAAV-TFPI-2 and co-cultured
      with fetal rat brain aggregates did not invade rat brain aggregates, whereas 90
      95% of the mock and AAV-CMV infected cells invaded rat brain aggregates. In vitro
      angiogenesis studies (tumor cells co-cultured with endothelial cells or
      endothelial cells seeded on matrigel) showed reduction of capillary-like
      structure formation in rAAV-TFPI-2-treated cells as compared to parental and mock
      transfected cells. In in vivo angiogenesis results demonstrated the formation of
      microvessels in SNB19 parental cells and this formation was inhibited when the
      SNB19 cells were infected with rAAV-TFPI-2. Further, we observed a large
      reduction of tumor growth in SNB19 cells treated with rAAV-TFPI-2 virus injected
      intracerebrally when compared to controls. Our study demonstrates that rAAV-TFPI
      2-mediated gene therapy offers a novel tool for the treatment of brain tumors.

PMID- 15723304
TI  - Altered extent, pattern and characteristics of microvascular density are
      indicators of neoplastic progression in the endometrium.
AB  - The occurrence, structure and extent of microvascular density were examined in
      normal endometria, hyperplasia of different types and adenocarcinomas of
      different degrees of differentiation to determine their biologic and clinical
      significance in tumor development and progression. Computer-assisted quantitative
      image analysis was carried out on 12,500 vessels in regard to vessel number,
      vessel volume, size, shape and extent of vessel antibody staining, with
      sensitivity and reproducibility exceeding 99%. The results showed the extent,
      pattern and characteristics of microvascular density to be intimately associated
      with extent of tumor development and degree of differentiation of the tumor.
      Vessel number increased with superficial location in normal endometrium, with
      increased degree of hyperplasia and atypia and with increased degree of
      dedifferentiation of adenocarcinoma. Increased vessel shape alterations were
      characteristic of atypical complex hyperplasia when compared to other types of
      hyperplasia. Vessel number, size and shape were similar in proliferative
      endometrium and simplex type hyperplasia, and microvascular density in atypical
      complex hyperplasia was similar to that in well-differentiated adenocarcinoma.
      The results indicated that vessel shape alterations occur during progression of
      hyperplasia and vessel size increase occurs in complex-type hyperplasia and in
      moderately differentiated adenocarcinomas. We conclude that microvascular density
      is associated with endometrial location and with specific patterns of alteration
      in different stages of endometrial disease. The results suggest potential
      clinical applications of vessel analysis for determination of clinical behavior
      of endometrial preneoplastic and neoplastic alterations.

PMID- 15723305
TI  - New findings in craniofacial dyssynostosis.

PMID- 15723306
TI  - Absence of KLF6 gene mutation in 71 hepatocellular carcinomas.

PMID- 15723309
TI  - Fecal and urinary excretion of aflatoxin B1 metabolites (AFQ1, AFM1 and AFB-N7
      guanine) in young Chinese males.
AB  - Our study was designed to assess the fecal and urinary excretion of 3 aflatoxin
      B1 (AFB1) metabolites, aflatoxins M1 (AFM1) and Q1 (AFQ1) and aflatoxin B1-N7
      guanine (AFB-N7-guanine) that are produced by the predominant forms of cytochrome
      P450 enzymes responsible for the biotransformation of AFB1. Fecal and urinary
      AFM1, AFQ1 and urinary AFB-N7-guanine were assessed in 83 young Chinese males
      selected from a larger population (n = 300) based on detectable urinary AFM1. The
      concentration of fecal AFQ1 (median 137 ng/g fresh weight, IQR 9.1 to 450) was
      approximately 60 times higher than that of AFM1 (2.3 ng/g, IQR 0.0 to 7.3). In
      urine, the median AFQ1 was 10.4 ng/ml (IQR 3.4 to 23.3), and the median AFM1 and
      AFB-N7-guanine 0.04 ng/ml (IQR 0.01 to 0.33) and 0.38 ng/ml (IQR 0.0 to 2.15),
      respectively. A subgroup (n = 14) with hepatitis B virus (HBV) infection had
      significantly higher fecal concentrations of AFQ1 (p = 0.043) and AFM1 (p =
      0.001) than those who were hepatitis B-virus antigen (HBsAg) negative, and the
      respective differences in urinary AFQ1 and AFM1 concentrations approached
      statistical significance (p = 0.054, p = 0.138). Our study demonstrates that AFQ1
      is excreted in urine and feces at higher levels than AFM1, and feces are an
      important route of excretion of these AFB1 metabolites. AFQ1 should be further
      assessed for its predictive value as a marker for exposure and risk of dietary
      aflatoxins.

PMID- 15723310
TI  - Myhre's syndrome in a girl with normal intelligence.

PMID- 15723311
TI  - Biliverdin, immune-mediated liver injury, and the Gigo effect.

PMID- 15723313
TI  - In vitro evolution and characterization of a ligase ribozyme adapted to acidic
      conditions: effect of further rounds of evolution.
AB  - A ligase ribozyme that accelerates the ligation reaction with an oligonucleotide
      under low pH conditions was identified by in vitro adaptation in a previous
      study. We examined the effects of further rounds of evolution to isolate a more
      active ribozyme. The ribozyme, which was obtained after four rounds of evolution,
      was randomly mutated, and the resultant RNA library was subjected to in vitro
      selection at low pH. One ribozyme isolated from the pool was found to react 8,000
      times faster than the original b1 ribozyme at pH 4. The reaction rate of the
      isolated ribozyme was enhanced at various pH values, and its pH dependence was
      less than that of the original ribozyme or the ribozyme selected with four rounds
      of evolution. The reaction rate of the isolated ribozyme was reduced in the
      presence of 3' primer, the sequence of which is complementary to the 3' primer
      binding site of the ligase ribozyme. This inhibition induced by the primer
      oligonucleotide binding to the ribozyme 3' region implies that the 3' region
      plays a role in the ligation reaction of the ribozyme.

PMID- 15723314
TI  - Heterotrophic high cell-density fed-batch cultures of the phycocyanin-producing
      red alga Galdieria sulphuraria.
AB  - Growth and phycocyanin production in batch and fed-batch cultures of the
      microalga Galdieria sulphuraria 074G, which was grown heterotrophically in
      darkness on glucose, fructose, sucrose, and sugar beet molasses, was
      investigated. In batch cultures, specific growth rates and yields of biomass dry
      weight on the pure sugars were 1.08-1.15 day-1 and 0.48-0.50 g g-1, respectively.
      They were slightly higher when molasses was the carbon source. Cellular
      phycocyanin contents during the exponential growth phase were 3-4 mg g-1 in dry
      weight. G. sulphuraria was able to tolerate concentrations of glucose and
      fructose of up to 166 g L-1 (0.9 M) and an ammonium sulfate concentration of 22 g
      L-1 (0.17 M) without negative effects on the specific growth rate. When the total
      concentration of dissolved substances in the growth medium exceeded 1-2 M, growth
      was completely inhibited. In carbon-limited fed-batch cultures, biomass dry
      weight concentrations of 80-120 g L-1 were obtained while phycocyanin accumulated
      to concentrations between 250 and 400 mg L-1. These results demonstrate that G.
      sulphuraria is well suited for growth in heterotrophic cultures at very high cell
      densities, and that such cultures produce significant amounts of phycocyanin.
      Furthermore, the productivity of phycocyanin in the heterotrophic fed-batch
      cultures of G. sulphuraria was higher than is attained in outdoor cultures of
      Spirulina platensis, where phycocyanin is presently obtained.

PMID- 15723315
TI  - Amish brittle hair syndrome gene maps to 7p14.1.
AB  - The brittle hair syndrome (BHS) is characterized by short stature, intellectual
      impairment, brittle hair, and decreased fertility in 20 members from a large
      Amish consanguineous kindred previously reported affected with this syndrome. We
      mapped the BHS gene by genome scan to chromosome 7p14.1. Evidence of linkage was
      supported by a maximum multipoint LOD score of 6 obtained with GENEHUNTER for the
      linkage interval defined by markers D7S484-D7S2422 distant by 17.2 cM. Two-point
      linkage analysis performed with SUPERLINK yielded a LOD score of 9.02 at theta =
      0 for marker D7S2497 located within that interval. Analysis of haplotypes
      homozygous-by-descent allowed fine mapping of the BHS gene within a 4.81 cM
      interval delimited by markers D7S2497 and D7S691, a region that spreads over 3.42
      Mb.

PMID- 15723317
TI  - Host response to hepatitis C virus.

PMID- 15723319
TI  - Peds-C.

PMID- 15723320
TI  - Bacterial translocation (BT) in cirrhosis.
AB  - Gut flora and bacterial translocation (BT) play an important role in the
      pathogenesis of the complications of cirrhosis. Research on the pathogenesis of
      BT and its clinical significance transcends established boundaries between
      microbiology, cell biology, intestinal pathophysiology, and immunology. This
      review delineates multiple mechanisms involved in the process of BT, with an
      emphasis on alterations in intestinal flora and mucosal barrier function,
      particularly immunological defense mechanisms. Current knowledge on the innate
      and adaptive immune response that allows a "friendly" communication between
      bacteria and host is summarized, and alterations occurring in cirrhosis that may
      facilitate BT are discussed. In addition, definition of a "pathological" BT is
      proposed together with an analysis of the anatomical site and route of BT.
      Finally, therapeutic approaches for the prevention of BT in experimental and
      human cirrhosis are reviewed. Future research in the field of BT in cirrhosis
      will allow the development of new therapeutic targets in the prevention of
      infections and other complications of cirrhosis.

PMID- 15723322
TI  - Antiviral treatment of recurrent hepatitis C after liver transplantation: the
      need for a multifaceted approach.

PMID- 15723321
TI  - The coagulopathy of cirrhosis: myth or reality?

PMID- 15723323
TI  - Another Notch to be added to the list of hepatocellular growth regulatory
      factors?

PMID- 15723324
TI  - Novel immobilized liposomal glucose oxidase system using the channel protein OmpF
      and catalase.
AB  - The reactivity of immobilized glucose oxidase-containing liposomes (IGOL)
      prepared in our previous work (Wang et al. [2003] Biotechnol Bioeng 83:444-453)
      was considerably improved here by incorporating the channel protein OmpF from
      Escherichia coli into the liposome membrane as well as by entrapping inside the
      liposome's aqueous interior not only glucose oxidase (GO), but also catalase
      (CA), both from Aspergillus niger. CA was used for decomposing the hydrogen
      peroxide produced in the glucose oxidation reaction inside the liposomes. The
      presence of OmpF enhanced the transport of glucose molecules from the exterior of
      the liposomes to the interior. In a first step of the work, liposomes containing
      GO and CA (GOCAL) were prepared and characterized. A remarkable protection effect
      of the liposome membrane on CA inside the liposomes at 40 degrees C was found;
      the remaining CA activity at 72 h incubation was more than 60% for GOCAL, while
      less than 20% for free CA. In a second step, OmpF was incorporated into GOCAL
      membranes, leading to the formation of OmpF-embedded GOCAL (abbreviated GOCAL
      OmpF). The activity of GO inside GOCAL-OmpF increased up to 17 times in
      comparison with that inside GOCAL due to an increased glucose permeation across
      the liposome bilayer, without any leakage of GO or CA from the liposomes. The
      optimal system was estimated to contain on average five OmpF molecules per
      liposome. Finally, GOCAL-OmpF were covalently immobilized into chitosan gel
      beads. The performance of this novel biocatalyst (IGOCAL-OmpF) was examined by
      following the change in glucose conversion, as well as by following the remaining
      GO activity in successive 15-h air oxidations for repeated use at 40 degrees C in
      an airlift bioreactor. IGOCAL-OmpF showed higher reactivity and reusability than
      IGOL, as well as IGOL containing OmpF (IGOL-OmpF). The IGOCAL-OmpF gave about 80%
      of glucose conversion even when the catalyst was used repeatedly four times,
      while the corresponding conversions were about 60% and 20% for the IGOL and IGOL
      OmpF, respectively. Due to the absence of CA, IGOL-OmpF was less stable and
      resulted in drastically inhibited GO.

PMID- 15723325
TI  - Potential of silver nanoparticle-coated polyurethane foam as an antibacterial
      water filter.
AB  - Silver nanoparticles can be coated on common polyurethane (PU) foams by overnight
      exposure of the foams to nanoparticle solutions. Repeated washing and air-drying
      yields uniformly coated PU foam, which can be used as a drinking water filter
      where bacterial contamination of the surface water is a health risk.
      Nanoparticles are stable on the foam and are not washed away by water. Morphology
      of the foam was retained after coating. The nanoparticle binding is due to its
      interaction with the nitrogen atom of the PU. Online tests were conducted with a
      prototypical water filter. At a flow rate of 0.5 L/min, in which contact time was
      of the order of a second, the output count of Escherichia coli was nil when the
      input water had a bacterial load of 10(5) colony-forming units (CFU) per mL.
      Combined with the low cost and effectiveness in its applications, the technology
      may have large implications to developing countries.

PMID- 15723327
TI  - Four novel NIPBL mutations in Japanese patients with Cornelia de Lange syndrome.

PMID- 15723328
TI  - "Strong reasons make strong actions"--The antiviral efficacy of NS3/4A protease
      inhibitors.

PMID- 15723329
TI  - Wilson disease in septuagenarian siblings: Raising the bar for diagnosis.
AB  - Wilson Disease (WD) usually presents in the first decades of life, although rare
      patients have a later presentation. We report the clinical features, diagnostic
      evaluation, and outcome with treatment of two septuagenarian siblings evaluated
      as part of a research trial for treatment of neurological WD. The index case was
      a 72-year-old woman who suffered progressive neurological disability, then
      developed sub-fulminant liver failure. Her sibling was a 70-year-old man with
      minimal neurological symptoms and a mild depressive disorder. His liver biopsy
      revealed only steatosis and minimal fibrosis and an elevated hepatic copper
      content (671 mug/g dry weight liver). Molecular studies demonstrated compound
      heterozygosity for disease specific ATP7B mutations E1064A and H1069Q in both
      patients. Both individuals were treated with trientine and Zn followed by Zn
      maintenance therapy. Over the last 5 years, the clinical course stabilized and
      improved, although the index case recently died from bronchopneumonia. In
      conclusion, advanced age and different clinical presentations of these two
      subjects with identical ATP7B mutations raises the question of the degree of
      penetrance for these and other ATP7B mutations. Environmental and extragenic
      factors are pivotal determinants of disease phenotype. We suggest that WD must be
      considered at all ages in patients with hepatic disease, neurological disease, or
      psychiatric symptoms.

PMID- 15723330
TI  - Hepatitis C virus and the threshold of natural killer cell inhibition.

PMID- 15723331
TI  - Staging for hepatocellular carcinoma: treatment strategy matters.

PMID- 15723332
TI  - Regiospecific oxidation of naphthalene and fluorene by toluene monooxygenases and
      engineered toluene 4-monooxygenases of Pseudomonas mendocina KR1.
AB  - The regiospecific oxidation of the polycyclic aromatic hydrocarbons naphthalene
      and fluorene was examined with Escherichia coli strains expressing wildtype
      toluene 4-monooxygenase (T4MO) from Pseudomonas mendocina KR1, toluene para
      monooxygenase (TpMO) from Ralstonia pickettii PKO1, toluene ortho-monooxygenase
      (TOM) from Burkholderia cepacia G4, and toluene/ortho-xylene monooxygenase (ToMO)
      from P. stutzeri OX1. T4MO oxidized toluene (12.1+/-0.8 nmol/min/mg protein at
      109 microM), naphthalene (7.7+/-1.5 nmol/min/mg protein at 5 mM), and fluorene
      (0.68+/-0.04 nmol/min/mg protein at 0.2 mM) faster than the other wildtype
      enzymes (2-22-fold) and produced a mixture of 1-naphthol (52%) and 2-naphthol
      (48%) from naphthalene, which was successively transformed to a mixture of 2,3-,
      2,7-, 1,7-, and 2,6-dihydroxynaphthalenes (7%, 10%, 20%, and 63%, respectively).
      TOM and ToMO made 1,7-dihydroxynaphthalene from 1-naphthol, and ToMO made a
      mixture of 2,3-, 2,6-, 2,7-, and 1,7-dihydroxynaphthalene (26%, 22%, 1%, and 44%,
      respectively) from 2-naphthol. TOM had no activity on 2-naphthol, and T4MO had no
      activity on 1-naphthol. To take advantage of the high activity of wildtype T4MO
      but to increase its regiospecificity on naphthalene, seven engineered enzymes
      containing mutations in T4MO alpha hydroxylase TmoA were examined; the
      selectivity for 2-naphthol by T4MO I100A, I100S, and I100G was enhanced to 88
      95%, and the selectivity for 1-naphthol was enhanced to 87% and 99% by T4MO I100L
      and G103S/A107G, respectively, while high oxidation rates were maintained except
      for G103S/A107G. Therefore, the regiospecificity for naphthalene oxidation was
      altered to practically pure 1-naphthol or 2-naphthol. All four wildtype
      monooxygenases were able to oxidize fluorene to different monohydroxylated
      products; T4MO oxidized fluorene successively to 3-hydroxyfluorene and 3,6
      dihydroxyfluorene, which was confirmed by gas chromatography-mass spectrometry
      and 1H nuclear magnetic resonance analysis. TOM and its variant TomA3 V106A
      oxidize fluorene to a mixture of 1-, 2-, 3-, and 4-hydroxyfluorene. This is the
      first report of using enzymes to synthesize 1-, 3-, and 4-hydroxyfluorene, and
      3,6-dihydroxyfluorene from fluorene as well as 2-naphthol and 2,6
      dihydroxynaphthalene from naphthalene.

PMID- 15723333
TI  - Association of deletion 22 and trisomy 21: a likely random association in
      patients with conotruncal heart defects.

PMID- 15723335
TI  - Re: Microcephalic osteodysplastic primordial dwarfism with severe microdontia and
      skin anomalies [Kantaputra et al. 2004. Am J Med Genet 130A:181-190].

PMID- 15723336
TI  - Induction of cytotoxicity in human lung adenocarcinoma cells by 6-O-carboxypropyl
      alpha-tocotrienol, a redox-silent derivative of alpha-tocotrienol.
AB  - Tocotrienols are one of the most potent anticancer agents of all natural
      compounds and the anticancer property may be related to the inactivation of Ras
      family molecules. The anticancer potential of tocotrienols, however, is weakened
      due to its short elimination half life in vivo. To overcome the disadvantage and
      reinforce the anticancer activity in tocotrienols, we synthesized a redox-silent
      analogue of alpha-tocotrienol (T3), 6-O-carboxypropyl-alpha-tocotrienol (T3E). We
      estimated the possibility of T3E as a new anticancer agent against lung
      adenocarcinoma showing poor prognosis based on the mutation of ras gene. T3E
      showed cytotoxicity against A549 cells, a human lung adenocarcinoma cell line
      with a ras gene mutation, in a dose-dependent manner (0-40 microM), whereas T3
      and a redox-silent analogue of alpha-tocopherol (T), 6-O-carboxypropyl-alpha
      tocopherol (TE), showed much less cytotoxicity in cells within 40 microM. T3E
      cytotoxicity was based on the accumulation of cells in the G1-phase of the cell
      cycle and the subsequent induction of apoptosis. Similar to this event, 24-hr
      treatment of A549 cells with 40 microM T3E caused the inhibition of Ras
      farnesylation, and a marked decrease in the levels of cyclin D required for G1/S
      progression in the cell-cycle and Bcl-xL, a key anti-apoptotic molecule.
      Moreover, the T3E-dependent inhibition of RhoA geranyl-geranylation is an
      inducing factor for the occurrence of apoptosis in A549 cells. Our results
      suggest that T3E suppresses Ras and RhoA prenylation, leading to negative growth
      control against A549 cells. In conclusion, a redox-silent analogue of T3, T3E may
      be a new candidate as an anticancer agent against lung adenocarcinoma showing
      poor prognosis based on the mutation of ras genes.

PMID- 15723337
TI  - Molecular cloning and characterization of FBXO47, a novel gene containing an F
      box domain, located in the 17q12 band deleted in papillary renal cell carcinoma.
AB  - Genetic alterations of chromosome arm 17q occur in numerous tumor types,
      including breast and ovarian tumors, suggesting the presence of a tumor
      suppressor gene on the long arm of chromosome 17 that is critical for
      carcinogenesis. Previous studies have shown an allelic imbalance (70% gain or
      loss) of 17q in papillary renal cell carcinoma (pRCC). In this study, we analyzed
      15 cases of pRCC for loss of heterozygosity with the use of 7 microsatellite
      markers between 17q11 and 17q23. We identified a minimal deleted region in which
      the D17S250 marker (17q12) was deleted in 50% (7 of 14) of informative cases. We
      isolated the cDNA of a novel gene named FBXO47, which is near D17S250. Human
      FBXO47 is composed of 11 exons and spans approximately 30 kb of genomic DNA.
      FBXO47 cDNA consists of 2,269 bp with a 1,359-bp open-reading frame. Of note is
      that FBXO47 is preferentially expressed in normal tissue relative to the
      corresponding tumor tissue, particularly in the kidney, liver, and pancreas and
      to a lesser extent in the thyroid gland, stomach, and small intestine. The
      putative protein encoded by this gene is made up of 453 amino acids and belongs
      to the F-box family, most of whose members, such as SKP2 and FBW7, have been
      implicated in carcinogenesis. Together, these results indicate that FBX047 has a
      potential role as a tumor-suppressor gene.

PMID- 15723338
TI  - Interpretation of submicroscopic deletions of the BCR or ABL gene should not
      depend on extra signal-FISH: problems in interpretation of submicroscopic
      deletion of the BCR or ABL gene with extra signal-FISH.
AB  - Several groups have demonstrated that a submicroscopic gene deletion in Ph+
      chronic myelogenous leukemia (CML) is associated with a poor prognosis and
      reduced response to treatment. To assess the variation between detection methods
      in the interpretation of a submicroscopic gene deletion, we performed an extra
      signal (ES)-FISH BCR/ABL and double-FISH (D-FISH) BCR/ABL on frozen bone marrow
      cells from 79 patients with CML (63 in the chronic phase, 6 in the accelerated
      phase, and 10 in blast crisis) and 30 patients with a BCR/ABL-negative
      myeloproliferative disorder as determined by RT-PCR. The normal cutoff values
      were 0.22% for ES-FISH and 0.25% for D-FISH. The cutoff values for false-positive
      signals from a juxtaposition of the BCR and ABL gene were 11% in ES-FISH and 13%
      in D-FISH. Of the 14 patients who showed an ABL gene deletion by ES-FISH, 5 had
      an ABL deletion only, 5 had both a BCR and an ABL deletion, but 4 proved to have
      a classic BCR/ABL rearrangement without a submicroscopic deletion, as determined
      by D-FISH. Discrepant results between ES- and D-FISH were observed in 12 of the
      79 patients (15.8%), and the main causes of a discrepancy were a false-positive
      ABL deletion (4 of 12, 33%), a variant Philadelphia chromosome (3 of 12, 25%), an
      inversion of derivative chromosome 9 at the very breakpoint of the ABL gene
      (9q32) (1 of 12, 8.3%), a cryptic variant Ph chromosome (1 of 12, 8.3%), and a
      marker chromosome (1 of 12, 8.3%). Although there was no significant difference
      in the sensitivity for the detection of the fusion signal between ES- and D-FISH,
      ES-FISH showed a high percentage of cells with false-positive fusion signals (1
      orange, 1 green, 1 yellow), which makes it difficult to interpret the
      submicroscopic ABL deletion. In conclusion, an interpretation of the
      submicroscopic deletions of the BCR or ABL gene should not depend on ES-FISH.

PMID- 15723339
TI  - MYND-less splice variants of AML1-MTG8 (RUNX1-CBFA2T1) are expressed in leukemia
      with t(8;21).
AB  - The AML1-MTG8 fusion gene is generated by chromosome translocation t(8;21), which
      is frequently observed in acute myeloid leukemia. The fusion gene produces a
      chimeric transcription factor that suppresses the expression of AML1-target genes
      via the MTG8 part of the chimeric protein, which is thought to be the primary
      cause of leukemia. The C-terminal region of MTG8 contains the MYND domain,
      represented by highly conserved zinc-finger-like protein motifs, and is known to
      interact with corepressor proteins. We found that, instead of the MYND domain, an
      alternative last exon of MTG8 encoding 27 amino acids in-frame is expressed
      naturally in human adult testis and in several leukemia cell lines. This type of
      alternative splicing also occurred in the AML1-MTG8 fusion gene at high levels in
      leukemia cell lines with t(8;21), as well as in blast cells of leukemia patients
      with t(8;21). The variant proteins of both MTG8 and AML1-MTG8 reduced
      transcriptional repressor activity in a mammalian two-hybrid assay. However,
      mixed expression of these variants with wild-type MTG8 recovered their repressor
      activity, suggesting that these variants also act as repressors in vivo where
      wild-type MTG8 and other family members exist in abundance. On the other hand,
      the MYND-less variants acquired a higher affinity for binding to MTG8 and formed
      a multimer, whereas the wild-type protein forms a dimer. Thus, expression of the
      MYND-less variants by the dysregulation of splicing machinery, which stimulates
      the oligomerization of fusion proteins in leukemia cells, may enhance malignant
      conversion of hematopoietic cells.

PMID- 15723340
TI  - Genetic changes and clonality relationship between primary colorectal cancers and
      their pulmonary metastases--an analysis by comparative genomic hybridization.
AB  - About 10% of colorectal carcinoma patients develop pulmonary metastases during
      their lifetime. We address whether and how the chromosomal abnormalities differ
      between the primary cancers and their metastatic counterparts, what the clonality
      relationship (CR) is between them, and whether certain genomic aberrations
      contribute to this disease progression. Comparative genomic hybridization (CGH)
      experiments were performed on 18 paired samples of primary and pulmonary
      metastases obtained from patients who had undergone two consecutive surgeries and
      from whom clinical data had been collected. The CGH profiles also were used as
      indexes for determining the CR between the cancers. The overall CGH abnormality
      profiles were similar for the primary colorectal carcinomas and their pulmonary
      metastases. Frequent gains were found on chromosome arms 20q, 8q, 13q, and 7q,
      whereas common losses were found on 18q, 8p, and 18p. The pulmonary metastases,
      however, contained more CGH abnormalities than did the primary carcinomas (total
      aberration events per tumor: 12.6 +/- 5.0 vs. 8.3 +/- 5.7, respectively, P =
      0.024; gains: 7.6 +/- 3.1 vs. 5.1 +/- 3.5, respectively, P = 0.036; losses: 5.0
      +/- 2.8 vs. 3.3 +/- 2.9, respectively, P = 0.076). Comparing CGH profiles between
      individual primary and metastasis pairs, we found that 10 of the 18 (56%) paired
      samples examined exhibited a high degree of CR, indicating that they were likely
      to have originated from the same clone and/or that not many additional
      chromosomal changes had occurred in the metastases, except for 4q loss, whose
      incidence was much higher in the metastases than in the primaries (60% vs. 10%; P
      = 0.030). Also, the primary tumors of the high-CR group carried more genomic
      aberrations, especially 8p loss, than did the primary tumors in the low-CR group.
      We found more chromosomal changes associated with the pulmonary metastases of
      colorectal cancer compared with the corresponding primary tumors. We concluded
      that primary cancers containing more genomic lesions, especially 8p losses, are
      more likely to metastasize to the lungs. Loss of 4q is potentially a
      supplementary factor contributing to the dissemination of this disease.

PMID- 15723341
TI  - Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and
      endonuclease G.
AB  - Toward the end of the 20th and beginning of the 21st centuries, clever in vitro
      biochemical complementation experiments and genetic screens from the laboratories
      of Xiaodong Wang, Shigekazu Nagata, and Ding Xue led to the discovery of two
      major apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase
      activated DNase (CAD) and endonuclease G (Endo G). Both endonucleases attack
      chromatin to yield 3'-hydroxyl groups and 5'-phosphate residues, first at the
      level of 50-300 kb cleavage products and next at the level of internucleosomal
      DNA fragmentation, but these nucleases possess completely different cellular
      locations in normal cells and are regulated in vastly different ways. In non
      apoptotic cells, DFF exists in the nucleus as a heterodimer, composed of a 45 kD
      chaperone and inhibitor subunit (DFF45) [also called inhibitor of CAD (ICAD-L)]
      and a 40 kD latent nuclease subunit (DFF40/CAD). Apoptotic activation of caspase
      3 or -7 results in the cleavage of DFF45/ICAD and release of active DFF40/CAD
      nuclease. DFF40's nuclease activity is further activated by specific chromosomal
      proteins, such as histone H1, HMGB1/2, and topoisomerase II. DFF is regulated by
      multiple pre- and post-activation fail-safe steps, which include the requirements
      for DFF45/ICAD, Hsp70, and Hsp40 proteins to mediate appropriate folding during
      translation to generate a potentially activatable nuclease, and the synthesis in
      stoichiometric excess of the inhibitors (DFF45/35; ICAD-S/L). By contrast, Endo G
      resides in the mitochondrial intermembrane space in normal cells, and is released
      into the nucleus upon apoptotic disruption of mitochondrial membrane permeability
      in association with co-activators such as apoptosis-inducing factor (AIF).
      Understanding further regulatory check-points involved in safeguarding non
      apoptotic cells against accidental activation of these nucleases remain as future
      challenges, as well as designing ways to selectively activate these nucleases in
      tumor cells.

PMID- 15723342
TI  - Codominant expression of genes coding for different sets of inducible salivary
      polypeptides associated with parotid hypertrophy in two inbred mouse strains.
AB  - Experimental mouse parotid hypertrophy has been associated with the expression of
      a number of isoproterenol-induced salivary proline-rich polypeptides (IISPs).
      Mouse salivary proline-rich proteins (PRPs) have been mapped both to chromosomes
      6 and 8. Recently, mice of two inbred strains (A/Snell and A. Swiss) have been
      found to differ drastically in the IISPs. In this study, mice of both strains
      were used for cross-breeding experiments addressed to define the pattern of
      inheritance of the IISP phenotype and to establish whether the IISPs are coded on
      a single or on several chromosomes. The IISP phenotype of individual mice was
      assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      of whole saliva collected after three daily stimulations by isoproterenol.
      Parental A/Snell and A. Swiss mice were homogeneous for distinctive strain
      associated IISP-patterns. First filial generation (F1) mice obtained from the
      cross of A/Snell with A. Swiss mice expressed with no exception both the A/Snell
      and A. Swiss IISPs (coexpression). In the second filial generation (F2) both
      parental IISP phenotypes reappeared together with a majority of mice expressing
      the F1-hybrid phenotype (1:2:1 ratio). Backcrosses of F1 x A/Snell and F1 x A.
      Swiss produced offsprings displaying the F1 and the corresponding parental
      phenotypes with a 1:1 ratio. No recombinants were observed among F2 mice or among
      mice resulting from backcrosses. Thus, genes coding for the IISPs that are
      expressed differentially in both mouse strains are located on the same
      chromosome, probably at the same locus (alleles) or at quite closely linked loci
      (nonalleles).

PMID- 15723343
TI  - BRCA1: a locus-specific "liaison" in gene expression and genetic integrity.
AB  - Mutations in BRCA1 predominantly lead to elevated risks of breast and ovarian
      cancers. In contrast to the tissue-specific nature of BRCA1tumors, the normal
      BRCA1 gene product functions in diverse nuclear events including transcription,
      DNA repair, and DNA damage checkpoint. Recent findings of physical and functional
      associations between BRCA1 and the RNA polymerase II (RNAPII)-dependent
      transcription machinery may shed some light on this longstanding paradox of BRCA1
      biology. Eukaryotic gene expression is now known to be a continuous process,
      whereby each step is physically and functionally connected to the next. In
      particular, RNAPII plays a pivotal role in coordinating transcription with
      various pre-mRNA processing events and stress response. Interestingly, BRCA1
      preferentially interacts with the processive form of RNAPII and proteins that
      regulate RNAPII activity and movement during transcription elongation. In
      response to DNA damage, BRCA1 dissociates from RNAPII and localizes to DNA damage
      sites. We propose that BRCA1 may coordinate multiple steps in gene expression,
      including transcription initiation, elongation, and pre-mRNA processing via its
      interactions with the transcription machinery at selected gene loci. The same
      BRCA1-associated transcription apparatus may serve as a sensor for stress signals
      and facilitate the transition from a transcription state to checkpoint/DNA repair
      state. Such a coordinating role of BRCA1 in gene expression may ensure the
      appropriate quantity and quality of the mature transcripts for certain breast and
      ovarian cancer-related genes, as well as the genetic integrity of the breast and
      ovary tissues.

PMID- 15723344
TI  - Histone modifications as a platform for cancer therapy.
AB  - Tumorigenesis and metastasis are a progression of events resulting from
      alterations in the processing of the genetic information. These alterations
      result from stable genetic changes (mutations) involving tumor suppressor genes
      and oncogenes (e.g., ras, BRAF) and potentially reversible epigenetic changes,
      which are modifications in gene function without a change in the DNA sequence.
      Mutations of genes coding for proteins that directly or indirectly influence
      epigenetic processes will alter the cell's gene expression program. Epigenetic
      mechanisms often altered in cancer cells are DNA methylation and histone
      modifications (acetylation, methylation, phosphorylation). This article will
      review the potential of these reversible epigenetic processes as targets for
      cancer therapies.

PMID- 15723345
TI  - Neural network-based prediction of mutation-induced protein stability changes in
      Staphylococcal nuclease at 20 residue positions.
AB  - Protein-based therapeutics are playing an increasingly important role in the
      treatment of diseases, including diabetes and cancer. The viability of these
      treatments, however, are highly dependent on the stability of the therapeutic,
      since stability affects both the shelf life of the therapeutic as well as its
      active life in the body. Stability engineering can, therefore, be used to
      increase the effectiveness of protein-based therapeutics. Computational methods
      of protein stability prediction have been under development for about a decade,
      but complex molecular interactions make stability prediction difficult and
      computationally intensive. A rapid computational method of protein stability
      prediction is developed using feed-forward neural networks and used to predict
      mutation-induced stability changes in Staphylococcal nuclease. The input to the
      neural network consisted of sequences of evolutionarily based amino acid
      similarity scores that were obtained through the comparison of the amino acids in
      a mutation containing sequence to their positional counterparts in the baseline
      wild-type amino acid sequence. A training set was created which consisted of
      similarity score sequences, for which the stabilities of the corresponding amino
      acid sequences were known, paired with the relative stabilities of the sequences
      to that of the baseline. Back-propagation of error was used to train the network
      to output accurate relative stability scores for the sequences in the training
      set. Neural network-based relative stability predictions for 55 sequences
      containing mutation combinations not found in the training set had an accuracy of
      92.8%.

PMID- 15723346
TI  - Regulation of striatal preproenkephalin mRNA levels in MPTP-lesioned mice treated
      with estradiol.
AB  - We reported previously the protective effect of 17beta-estradiol (17beta-E(2)) on
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine (DA)
      depletion. This protection was stereospecific, because 17beta-E(2) showed
      activity but 17alpha-estradiol (17alpha-E(2)) did not. The mechanisms by which
      estradiol exerts its beneficial effects, however, remain unknown. We investigated
      a possible implication of enkephalins (ENK) in neuroprotective activity of 17beta
      E(2). Protection against MPTP-induced DA depletion was obtained with 17beta-E(2)
      but not 17alpha-E(2). MPTP lesion increased striatal preproenkephalin (PPE) mRNA
      levels and they remained elevated in 17alpha-E(2)-treated MPTP mice whereas
      17beta-E(2) treatment decreased these levels to control values. This is the first
      report of estradiol modulation of striatal PPE mRNA in mice. Negative and
      significant correlations between DA levels, vesicular monoamine transporter
      (VMAT(2)) density, and PPE mRNA were observed in the striatum of lesioned
      animals. This effect of 17beta-E(2) on PPE mRNA after a lesion could be one of
      many mechanisms by which this steroid exerts its neuroprotective activity.

PMID- 15723347
TI  - Properties of integral membrane protein structures: derivation of an implicit
      membrane potential.
AB  - Distributions of each amino acid in the trans-membrane domain were calculated as
      a function of the membrane normal using all currently available alpha-helical
      membrane protein structures with resolutions better than 4 A. The results were
      compared with previous sequence- and structure-based analyses. Calculation of the
      average hydrophobicity along the membrane normal demonstrated that the protein
      surface in the membrane domain is in fact much more hydrophobic than the protein
      core. While hydrophobic residues dominate the membrane domain, the interfacial
      regions of membrane proteins were found to be abundant in the small residues
      glycine, alanine, and serine, consistent with previous studies on membrane
      protein packing. Charged residues displayed nonsymmetric distributions with a
      preference for the intracellular interface. This effect was more prominent for
      Arg and Lys resulting in a direct confirmation of the positive inside rule.
      Potentials of mean force along the membrane normal were derived for each amino
      acid by fitting Gaussian functions to the residue distributions. The individual
      potentials agree well with experimental and theoretical considerations. The
      resulting implicit membrane potential was tested on various membrane proteins as
      well as single trans-membrane alpha-helices. All membrane proteins were found to
      be at an energy minimum when correctly inserted into the membrane. For alpha
      helices both interfacial (i.e. surface bound) and inserted configurations were
      found to correspond to energy minima. The results demonstrate that the use of
      trans-membrane amino acid distributions to derive an implicit membrane
      representation yields meaningful residue potentials.

PMID- 15723348
TI  - NMR structure of the conserved hypothetical protein TM0979 from Thermotoga
      maritima.

PMID- 15723349
TI  - Solution NMR structure of the SH3 domain of human nephrocystin and analysis of a
      mutation-causing juvenile nephronophthisis.
AB  - Human nephrocystin is a protein associated with juvenile NPH, an autosomal
      recessive, inherited kidney disease responsible for chronic renal failure in
      children. It contains an SH3 domain involved in signaling pathways controlling
      cell adhesion and cytoskeleton organization. The solution structure of this
      domain was solved by triple resonance NMR spectroscopy. Within the core, the
      structure is similar to those previously reported for other SH3 domains but
      exhibits a number of specific noncanonical features within the polyproline ligand
      binding site. Some of the key conserved residues are missing, and the N-Src loop
      exhibits an unusual twisted geometry, which results in a narrowing of the binding
      groove. This is induced by the replacement of a conserved Asp, Asn, or Glu
      residue by a Pro at one side of the N-Src loop. A systematic survey of other SH3
      domains also containing a Pro at this position reveals that most of them belong
      to proteins involved in cell adhesion or motility. A variant of this domain,
      which carries a point mutation causing NPH, was also analyzed. This change,
      L180P, although it corresponds to a nonconserved and solvent-exposed position,
      causes a complete loss of the tertiary structure. Similar effects are also
      observed with the L180A variant. This could be a context-dependent effect
      resulting from an interaction between neighboring charged side-chains.

PMID- 15723350
TI  - Molecular dynamics simulation of sucrose- and trehalose-coated carboxy-myoglobin.
AB  - We performed a room temperature molecular dynamics (MD) simulation on a system
      containing 1 carboxy-myoglobin (MbCO) molecule in a sucrose-water matrix of
      identical composition (89% [sucrose/(sucrose + water)] w/w) as for a previous
      trehalose-water-MbCO simulation (Cottone et al., Biophys J 2001;80:931-938).
      Results show that, as for trehalose, the amplitude of protein atomic mean-square
      fluctuations, on the nanosecond timescale, is reduced with respect to aqueous
      solutions also in sucrose. A detailed comparison as a function of residue number
      evidences mobility differences along the protein backbone, which can be related
      to a different efficacy in bioprotection. Different heme pocket structures are
      observed in the 2 systems. The joint distribution of the magnitude of the
      electric field at the CO oxygen atom and of the angle between the field and the
      CO unit vector shows a secondary maximum in sucrose, absent in trehalose. This
      can explain the CO stretching band profile (A substates distribution) differences
      evidenced by infrared spectroscopy in sucrose- and trehalose-coated MbCO
      (Giuffrida et al., J Phys Chem B 2004;108:15415-15421), and in particular the
      appearance of a further substate in sucrose. Analysis of hydrogen bonds at the
      protein-solvent interface shows that the fraction of water molecules shared
      between the protein and the sugar is lower in sucrose than in trehalose, in spite
      of a larger number of water molecules bound to the protein in the former system,
      thus indicating a lower protein-matrix coupling, as recently observed by Fourier
      transform infrared (FTIR) experiments (Giuffrida et al., J Phys Chem B
      2004;108:15415-15421).

PMID- 15723351
TI  - Zinc modulation of serotonin uptake in the adult rat corpus callosum.
AB  - Antidepressants partially inhibit the uptake of 5-hydroxytryptamine (5-HT;
      serotonin) in the rat corpus callosum (CC), a white matter commissure involved in
      interhemispheric brain communication. It is also known that zinc modulates many
      proteins, including neurotransmitter transporters. We examined the effects of
      zinc on the uptake of 5-HT into slices of the adult rat CC, in the absence or
      presence of some antidepressants. Zinc increased 5-HT uptake in a concentration
      dependent manner when the CC slices were incubated in a solution buffered with
      sodium bicarbonate; however, zinc exerted no effect on 5-HT transport when HEPES
      was the buffer. Potentiation of 5-HT uptake by zinc was maximal with 1 microM
      (45% over the control uptake). Moreover, 1 microM zinc potentiated 5-HT uptake in
      the cingulate cortex by 58% and in the Raphe nucleus by 65%. The antidepressants
      fluoxetine and imipramine inhibited 5-HT uptake in the CC by approximately 50%,
      whereas 6-nitroquipazine, a potent 5-HT uptake blocker, inhibited uptake by only
      23%. Interestingly, inhibition of 5-HT uptake by all three substances,
      fluoxetine, imipramine, and 6-nitroquipazine, was counteracted by the presence of
      1 microM zinc. Free zinc may thus contribute to modulation of extracellular
      levels of 5-HT and its removal. These actions should be considered in the
      treatment of mental depression with antidepressants.

PMID- 15723352
TI  - Helicobacter pylori protein HP0222 belongs to Arc/MetJ family of transcriptional
      regulators.
AB  - Helicobacter pylori is a widespread human bacterial pathogen responsible for
      inducing gastric and duodenal ulcers and gastric cancers. To date, only 16
      protein structures from this organism have been determined, and more than 30% of
      its 1500 protein functions remain unknown. We report the biochemical
      characterization, the tertiary structure determined by solution nuclear magnetic
      resonance (NMR) methods and the putative function of the previously
      uncharacterized protein HP0222 (JHP0208) from H. pylori. Recombinant HP0222
      behaves as a dimer in crosslinking and size exclusion chromatography experiments.
      The structure consists of a ribbon-helix-helix fold characteristic of
      transcription factors of the Arc/MetJ family, which all bind DNA as higher order
      oligomers. Electrophoretic mobility shift assays reveal that HP0222 binds to
      double-stranded DNA. Previous studies have shown significant increases in
      transcription levels of HP0222 in response to acid shock and adherence to gastric
      epithelial cells. To assess possible involvement of HP0222 in acid resistance, we
      constructed and assayed an H. pylori HP0222 null mutant. We propose that HP0222
      is a novel transcriptional regulator in H. pylori.

PMID- 15723353
TI  - Neuroserpin (PI-12) is upregulated in high-grade prostate cancer and is
      associated with survival.
AB  - We carried out Genechip analysis using prostate cancer and non-malignant tissue
      to identify specific genes related to prostate cancer. We focused on neuroserpin
      (PI-12), which has been identified as one of the genes with high expression in
      prostate cancer. We analyzed the relationship between its expression pattern and
      clinical characteristics. Prostate cancer and normal prostate tissue were
      analyzed by Affymetrix GeneChip technology. We carried out real-time quantitative
      PCR on a total of 102 specimens: 45 of normal prostate, 45 of previously
      untreated prostate cancer (constituting 45 pairs of samples obtained at radical
      prostatectomy, with each pair dissected from the same prostate specimen) and 12
      of recurrent hormone refractory prostate cancer (HRPC). Results showed that the
      neuroserpin gene was more highly expressed in prostate cancer than in normal
      prostate tissue. Neuroserpin expression in untreated prostate cancer was
      significantly higher than that in normal prostate. In HRPC it was significantly
      higher than that in untreated prostate cancer and normal prostate. In untreated
      prostate cancer, neuroserpin expression was significantly higher in high grade
      tumors such as poorly differentiated adenocarcinoma than in lower grade tumors
      such as well or moderately differentiated adenocarcinoma. Higher neuroserpin
      expression was associated with shorter recurrence-free survival after radical
      prostatectomy, shorter recurrence-free survival in HRPC patients and shorter
      overall survival in HRPC patients. The neuroserpin gene may be associated with
      the development, progression and aggressiveness of prostate cancer. Our present
      data suggests that higher neuroserpin expression may predict an unfavorable
      outcome after radical prostatectomy or hormone therapy.

PMID- 15723354
TI  - Response of malignant B lymphocytes to ionizing radiation: gene expression and
      genotype.
AB  - The human malignant B-lymphocyte cell lines Reh and U698 show arrest in G2 phase
      after ionizing radiation (IR), but only Reh cells arrest in G1 phase and die by
      apoptosis. We have used cDNA microarrays to measure changes in gene expression at
      2, 4 and 6 hr after irradiation of Reh and U698 cells with 0.5 and 4 Gy in order
      to begin exploring the molecular mechanisms underlying the phenotypic changes. We
      also investigated whether gene expression changes could be caused by possible
      aberrations of genes, as measured by comparative genomic hybridization. Reh cells
      showed upregulation of CDKN1A that likely mediated the G1 arrest. In contrast,
      U698 cells have impaired function of TP53 protein and no activation of CDKN1A,
      suppressing the arrest in G1. The G2 arrest in both cell lines was likely due to
      repression of PLK1 and/or CCNF. IR-induced apoptosis in Reh cells was probably
      mediated by TP53 and CDKN1A, whereas a high expression level of MCL1, caused by
      gene amplification, and activation of the NFKB pathway may have suppressed the
      apoptotic response in U698 cells. Genes suggested to be involved in apoptosis
      were activated long before this phenotype was detectable and showed the same
      temporal expression profiles as genes involved in cell cycle arrest. Our results
      suggest that differences in functionality and/or copy number of several genes
      involved in IR-regulated pathways contributed to the phenotypic differences
      between Reh and U698 cells after IR, and that multiple molecular factors control
      the radiation response of malignant B lymphocytes.

PMID- 15723355
TI  - Lithium-mediated downregulation of PKB/Akt and cyclin E with growth inhibition in
      hepatocellular carcinoma cells.
AB  - We studied in vitro effects of glycogen synthase kinase 3beta (GSK3beta)
      inhibitor lithium on the growth of hepatocellular carcinoma (HCC) cells. Lithium
      induced strong growth inhibition (> 70%) in 75% (n = 9 of 12) of cell lines,
      apparently independent from the status of major genes that are mutated in HCC
      including p53, p16(INK4a), beta-catenin and Axin1. Comparative studies with a
      growth-sensitive Huh7 and growth-resistant Hep40 cell lines showed that lithium
      induces growth arrest in Huh7 cells but not in Hep40 cells. Lithium induced the
      accumulation of N-terminally phosphorylated inactive form of GSK3beta with
      concomitant increase in beta-catenin and beta-catenin/TCF transcriptional
      activity in both cell lines. This suggests that lithium-mediated HCC growth
      inhibition is independent of its well-known stimulatory effect on Wnt-beta
      catenin signaling. The main differences between Huh7 and Hep40 responses to
      lithium treatment were observed at the levels PKB/Akt and cyclin E proteins.
      Lithium induced depletion of both proteins in growth-sensitive Huh7, but not in
      growth-resistant Hep40 cells. PKB/Akt and Cyclin E are 2 major proteins that are
      known to be constitutively active in HCC. The targeting of both proteins with
      lithium may be the main reason why most HCC cells are responsive to lithium
      mediated growth inhibition, independent of their p53, retinoblastoma and Wnt-beta
      catenin pathways. The exploration of molecular mechanisms involved in lithium
      mediated growth inhibition in relation with PKB/Akt and cyclin E downregulation
      may provide new insights for therapy of liver tumors.

PMID- 15723356
TI  - An 8.5-kb segment of the PMP22 promoter responds to loss of axon signals during
      Wallerian degeneration, but does not respond to specific axonal signals during
      nerve regeneration.
AB  - Altered expression of the PMP22 gene causes Charcot-Marie-Tooth disease type 1A
      (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). We
      have examined the promoter activity of 8.5 kb upstream of the first coding exon
      of the rat peripheral myelin protein-22 (rPmp22) gene in transgenic mice. We
      found that the -8.5 kb rPmp22/chloramphenicol acetyl transferase (CAT)/beta
      galactosidase (lacZ) construct directs reporter gene expression in a weakly
      developmental and tissue-specific pattern, consistent with the expression pattern
      of the endogenous Pmp22 gene. The -8.5 kb rPmp22/CAT/lacZ transgene responds to
      loss of axonal signals during Wallerian degeneration but unlike the endogenous
      Pmp22 gene, the transgene fails to respond to axonal signals during nerve
      regeneration after a sciatic nerve crush injury. In conclusion, the function of
      the -8.5 kb rPmp22/CAT/lacZ transgene suggests that there are separable
      regulatory elements in the rPmp22 gene that respond differently to axonal signals
      received by Schwann cells during nerve development, and during remyelination.

PMID- 15723357
TI  - Yeast (ADPribosyl)ation: revisiting a controversial question.
AB  - The controversy about the occurrence of an (ADPribosyl)ating activity in yeast is
      still standing up. Here we discuss this topic on the basis of results obtained
      with classic experiments proposed over years as basis to characterize an
      (ADPribosyl)ation system in any organism. Independent results obtained in two
      different laboratories were in line with each other and went towards the
      occurrence of an active (ADPribosyl)ating system in Saccharomyces cerevisiae. In
      fact data collected from nuclear preparations of cultured cells matched those
      from baker's yeast and lyophilized yeast cells. Yeast (ADPribosyl)ating enzyme is
      a protein of 80-90 kDa, as determined by electrophoresis on polyacrylamide gel in
      sodium dodecyl sulphate, followed by immunoblotting with antibodies against anti
      poly(ADPribose) polymerase catalytic site. It synthesizes products, that, after
      digestion with phosphodiesterase, co-migrates mainly with phosphoribosyl
      adenosine monophosphate after thin layer chromatography on silica gel plate.

PMID- 15723358
TI  - IGF-I, IGF binding protein-3 and breast cancer risk: comparison of 3 meta
      analyses.

PMID- 15723359
TI  - Thermal unfolding simulations of a multimeric protein--transition state and
      unfolding pathways.
AB  - The folding of an oligomeric protein poses an extra challenge to the folding
      problem because the protein not only has to fold correctly; it has to avoid
      nonproductive aggregation. We have carried out over 100 molecular dynamics
      simulations using an implicit solvation model at different temperatures to study
      the unfolding of one of the smallest known tetramers, p53 tetramerization domain
      (p53tet). We found that unfolding started with disruption of the native
      tetrameric hydrophobic core. The transition state for the tetramer to dimer
      transition was characterized as a diverse ensemble of different structures using
      Phi value analysis in quantitative agreement with experimental data. Despite the
      diversity, the ensemble was still native-like with common features such as
      partially exposed tetramer hydrophobic core and shifts in the dimer-dimer
      arrangements. After passing the transition state, the secondary and tertiary
      structures continued to unfold until the primary dimers broke free. The free
      dimer had little secondary structure left and the final free monomers were random
      coil like. Both the transition states and the unfolding pathways from these
      trajectories were very diverse, in agreement with the new view of protein
      folding. The multiple simulations showed that the folding of p53tet is a mixture
      of the framework and nucleation-condensation mechanisms and the folding is
      coupled to the complex formation. We have also calculated the entropy and
      effective energy for the different states along the unfolding pathway and found
      that the tetramerization is stabilized by hydrophobic interactions.

PMID- 15723360
TI  - A multibody, whole-residue potential for protein structures, with testing by
      Monte Carlo simulated annealing.
AB  - A new multibody, whole-residue potential for protein tertiary structure is
      described. The potential is based on the local environment surrounding each main
      chain alpha carbon (CA), defined as the set of all residues whose CA coordinates
      lie within a spherical volume of set radius in 3-dimensional (3D) space
      surrounding that position. It is shown that the relative positions of the CAs in
      these local environments belong to a set of preferred templates. The templates
      are derived by cluster analysis of the presently available database of over 3000
      protein chains (750,000 residues) having not more than 30% sequence similarity.
      For each template is derived also a set of residue propensities for each
      topological position in the template. Using lookup tables of these derived
      templates, it is then possible to calculate an energy for any conformation of a
      given protein sequence. The application of the potential to ab initio protein
      tertiary structure prediction is evaluated by performing Monte Carlo simulated
      annealing on test protein sequences.

PMID- 15723361
TI  - Neurofeedback in adolescents and adults with attention deficit hyperactivity
      disorder.
AB  - Neurofeedback is being utilized more commonly today in treating individuals who
      have attention deficit hyperactivity disorder (ADHD). Neurofeedback, which is
      based on theories that recognize the organic basis of ADHD, utilizes biofeedback
      to guide individuals to regulate their brain activity. Neurofeedback relies on
      research that has demonstrated that most individuals who have ADHD, as compared
      to matched peers, have excess slow wave activity and reduced fast wave activity.
      It provides immediate feedback to the individual about his or her brain wave
      activity in the form of a video game, whose action is influenced by the
      individual's meeting predetermined thresholds of brain activity. Over several
      sessions of using the video and auditory feedback, individuals reduce their slow
      wave activity and/or increase their fast wave activity. Individuals who complete
      a course of training sessions often show reduced primary ADHD symptoms. Research
      has shown that neurofeedback outcomes compare favorably to those of stimulant
      medication.

PMID- 15723362
TI  - Tunable imaging of cells labeled with MRI-PARACEST agents.

PMID- 15723363
TI  - Polyazide chemistry: the first binary group 6 azides, Mo(N3)6, W(N3)6, [Mo(N3)7]
      , and [W(N3)7]-, and the [NW(N3)4]- and [NMo(N3)4]- ions.

PMID- 15723364
TI  - A doubly N-fused benzohexaphyrin and its rearrangement to a fluorescent
      macrocycle upon DDQ oxidation.

PMID- 15723365
TI  - Real-time Fourier velocity encoding: an in vivo evaluation.
AB  - PURPOSE: To compare in vivo real-time Fourier velocity encoding (FVE), spectral
      Doppler ultrasound, and phase-contrast (PC) magnetic-resonance (MR) imaging.
      MATERIALS AND METHODS: In vivo velocity spectra were measured in the suprarenal
      and infrarenal aorta and the hepatic segment of the inferior vena cava of eight
      normal volunteers using FVE, and compared to similar measurements using Doppler
      ultrasound and gated PC MR imaging. In vivo waveforms were compared qualitatively
      according to flow pattern appearance (number, shape, and position of velocity
      peaks) and quantitatively according to peak velocity. RESULTS: Good agreement was
      obtained between peak velocities measured in vitro using FVE and PC MR imaging
      (R(2) = 0.99, P = 2.10(-6), slope = 0.97 +/- 0.05). Qualitatively, the FVE and
      ultrasound measurements agreed closely in the majority of in vivo cases
      (excellent or good in 21/24 cases) while the PC MR method resolved fewer velocity
      peaks due to the inherent temporal averaging of cardiac-gated studies (excellent
      or good agreement with FVE in 13/24 cases). Quantitatively, the FVE measurement
      of peak velocity correlated strongly with both ultrasound (R(2) = 0.71, P = 2.10(
      7), slope = 0.81 +/- 0.08) and PC MR (R(2) = 0.85, P = 2.10(-10), slope = 1.04 +/
      0.08). CONCLUSION: Real-time MR assessment of blood-flow velocity correlated
      well with spectral Doppler ultrasound. Such new methods may allow hemodynamic
      information to be acquired in vessels inaccessible to ultrasound or in patients
      for whom respiratory compensation is not possible.

PMID- 15723366
TI  - Psychosocial treatments for ADHD in teens and adults: a practice-friendly review.
AB  - Although stimulant medication is a cornerstone of treatment for attention deficit
      hyperactivity disorder (ADHD), numerous nonpharmacological treatments can be
      employed in combination with medication to assist in the lifelong management of
      the disorder. A multimodal treatment combining psychoeducation, medication,
      psychotherapy, compensatory behavioral/self-management skills, technological
      tools and devices, coaching, advocacy, and reasonable school or workplace
      accommodations is probably the most comprehensive and effective. This article
      describes a variety of psychosocial treatments that are commonly used for
      adolescents and adults suffering from ADHD.

PMID- 15723367
TI  - Measurement of cervical spinal cord cross-sectional area by MRI using edge
      detection and partial volume correction.
AB  - PURPOSE: To detail a procedure to accurately measure upper cervical cord cross
      sectional area (CSA), using MRI, by correcting for partial volume averaging
      (PVA), and to assess the usefulness of the procedure for measuring cervical cord
      atrophy rates in longitudinal studies. MATERIALS AND METHODS: Analysis of errors
      associated with measuring CSA in the presence of PVA is given. A numerical
      phantom image is produced, including simulated acquisition noise, to assess
      accuracy of the method in idealized conditions, and to verify the results of the
      error analysis. A phantom, consisting of 11 rods of known CSA, was scanned 10
      times and measurement accuracy assessed. A total of 10 normal subjects were
      scanned twice to assess the reproducibility under experimental conditions.
      RESULTS: The measurement error for the numerical phantom increased with increased
      simulated acquisition noise, as predicted by the analysis. Measurement of the
      plastic phantom revealed a systematic overestimate in CSA due to limited scanner
      accuracy of 3.15%. The scan-rescan error for the CSA of the cervical spine in the
      10 normal subjects was 0.55%. CONCLUSION: Correcting for PVA allows accurate
      measurement of the upper cervical cord CSA and accurate measurement of a standard
      phantom to guard against scanner drift in longitudinal studies of cord CSA.

PMID- 15723368
TI  - Comparison between three-dimensional volume-selective turbo spin-echo imaging and
      two-dimensional ultrasound for assessing carotid artery structure and function.
AB  - PURPOSE: To compare a volume-selective three-dimensional turbo spin echo (TSE)
      technique with ultrasound (US) for assessing carotid artery wall structure and
      function. MATERIALS AND METHODS: A three-dimensional volume-selective TSE
      technique was used to image the carotid artery in 10 healthy subjects and five
      hypertensive subjects (each of whom were scanned three times while they received
      different hypertension treatments). Lumen and wall area were measured on MR
      images. Two-dimensional US measurements of the intima-media thickness (IMT) and
      lumen diameter were taken in three orientations through a single cross section.
      The lumen area change over the cardiac cycle was used to determine distension.
      For validation, a Bland-Altman analysis was used to compare the vessel wall and
      lumen areas measured by three-dimensional MRI volumes with those obtained by US
      scans. RESULTS: Agreement between the two methods was found. The mean difference
      in distension between US and MRI was 1.2% (+/-5.1%). For the wall area
      measurements, good agreement was shown, but there was a systematic difference due
      to the visualization of the adventitia by MRI. Both techniques offer an easy way
      to objectively measure lumen indices. MRI can provide the complete circumference
      over the length of a vessel, while US is flexible and relatively inexpensive. The
      application of US is limited, however, when subjects are poorly echogenic. A
      difference between hypertensive and healthy subjects was found. CONCLUSION: There
      was a good agreement between MRI and the clinically established two-dimensional
      US method. The MRI method has the advantage of providing increased vessel
      coverage, which permits one to assess localized abnormalities without assuming
      vessel uniformity.

PMID- 15723369
TI  - Comparison of tumor blood perfusion assessed by dynamic contrast-enhanced MRI
      with tumor blood supply assessed by invasive imaging.
AB  - PURPOSE: To evaluate the potential of Gd-DTPA-based dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) for providing high-resolution tumor blood
      perfusion images. MATERIALS AND METHODS: Xenografted tumors from two amelanotic
      human melanoma lines (A-07 and R-18) were used as preclinical models of human
      cancer. DCE-MRI was performed at a voxel size of 0.5 x 0.2 x 2.0 mm(3) with the
      use of spoiled gradient recalled sequences. We produced tumor images of E . F
      (where E is the initial extraction fraction, and F is perfusion) by subjecting
      the DCE-MRI data to Kety analysis, and then compared those images with images of
      tumor blood supply. We obtained high-resolution tumor blood supply images using
      the Bioscope silicon strip detector system to measure the uptake of Na(99m)TcO(4)
      in histological preparations. We assessed the global blood supply by measuring
      the tumor uptake of three freely diffusible blood flow tracers: (86)RbCl,
      [(14)C]IAP, and Na(99m)TcO(4). RESULTS: E . F was found to mirror the blood
      supply well in A-07 and R-18 tumors. The mean E . F differed between the A-07 and
      R-18 tumors by a factor of approximately 1.6, and this difference was similar to
      the difference in the global blood supply. The intratumor heterogeneity in E . F
      was significant for tumors of both lines, and this heterogeneity was similar to
      the intratumor heterogeneity in the blood supply. The intratumor heterogeneity in
      the blood supply differed slightly between the A-07 and R-18 tumors, and even
      this difference was mirrored by the E . F images. CONCLUSION: E . F images of
      xenografted tumors reflect blood perfusion. This implies that E . F may be a
      useful parameter for improving cancer diagnostics and individualizing cancer
      treatment. This possibility deserves to be investigated thoroughly in clinical
      studies.

PMID- 15723370
TI  - An automated algorithm for combining multivoxel MRS data acquired with phased
      array coils.
AB  - PURPOSE: To develop a fully automated algorithm for combining multivoxel magnetic
      resonance spectroscopy (MRS) data acquired with a phased-array coil. MATERIALS
      AND METHODS: The frequency-domain fitting method of LCModel (Provencher SW, Magn
      Reson Med 1993;30:672-679) was utilized to analyze the individual data sets. The
      phase corrections and the metabolite areas were then extracted from the LCModel
      output files for each individual spectrum. These areas were used to determine the
      dominant metabolite for each spatial location and to combine the individual
      spectra in a weighted manner. RESULTS: The combination of MRS data acquired from
      a phantom and the brains of normal volunteers with a four array coil yielded
      improved signal-to-noise ratio (SNR) in all voxels. The average improvement in
      SNR of the combined spectrum, as compared with the best of the individual spectra
      at each spatial location, was 1.4. In the phantom, the predicted SNR improvement
      of two-fold was achieved at the center of the sample. In the brain, the maximum
      improvement was 1.8, due to sampling of the ventricles in the center of the
      sample. CONCLUSION: The method described in this report provides a means for
      employing phased-array coils in MRS with the same advantages as those found in
      MRI.

PMID- 15723371
TI  - A semiautomated technique for evaluation of uterine peristalsis.
AB  - PURPOSE: To evaluate the capability of a newly developed semiautomatic analysis
      technique for evaluation of uterine peristalsis in comparison with visual
      assessment. MATERIALS AND METHODS: Cine magnetic resonance (MR) images were
      obtained from 16 normal volunteers in periovulatory phase. Sixty-eight studies
      were evaluated by both visual evaluation and by a semiautomated computer assisted
      software. The software was developed by applying an automated contour tracking
      method and enables objective analysis of frequency, amplitude, velocity, and
      direction. Assessments were based on: 1) the recognition of peristalsis, 2)
      peristaltic direction and frequency, and 3) the way of recognizing peristaltic
      direction. The data obtained by both modalities were compared with those of
      previously reported ultrasound (US) findings. RESULTS: Uterine peristalsis was
      identified in all studies by both objective and visual analyses. There was no
      significant difference in the identification of peristalsis, recognition of
      peristaltic directions, or peristaltic frequency (P > 0.05). Data were well in
      accordance with those in US literature. Peristaltic direction was recognized
      either by configuration change in the endometrium or by conduction of low signal
      intensity in the subendometrial myometrium and there was statistically no
      difference. CONCLUSION: Evaluation of uterine peristalsis by the semiautomatic
      analysis accorded well with the results obtained visual assessments and previous
      US findings.

PMID- 15723372
TI  - Water-saturated three-dimensional balanced steady-state free precession for fast
      abdominal fat quantification.
AB  - PURPOSE: To compare the performance of a novel water-saturated b-SSFP sequence
      with that of a conventional T1-weighted turbo spin echo (T1W TSE) sequence for
      abdominal fat quantification. MATERIALS AND METHODS: A water-saturated,
      segmented, three-dimensional balanced steady-state free precession (b-SSFP)
      sequence and a traditional T1W TSE sequence were both employed on phantom and
      human studies. For phantom studies, a dual-layered phantom with known
      internal/external oil volumes was imaged using the two sequences. Images obtained
      by the two sequences were both processed using a computer-aided semiautomatic
      program for oil volume quantification. For human studies, six volunteers were
      scanned axially, centered at L2-L3 levels. Signal-to-noise ratio (SNR)(fat),
      contrast-to-noise ratio (CNR)(fat-muscle), CNR(fat-large bowel), and CNR(fat
      small bowel) were calculated on hand-drawn regions of interest (ROIs), and
      averaged over all six slices for each subject. Statistical analyses were then
      performed to determine the SNR and CNR differences between images obtained by the
      two techniques. RESULTS: The phantom studies show that water-saturated b-SSFP
      offers a significantly closer estimation of true oil volumes compared with that
      of T1W TSE (P < 0.0001), as well as a more accurate internal/external volume
      ratio (P = 0.0001). In human studies, three-dimensional water-saturated b-SSFP
      images demonstrated higher CNR than that of T1W TSE (P < 0.0005), and very close
      SNR(fat) (P = 0.045). CONCLUSION: The proposed three-dimensional water-saturated
      b-SSFP sequence can generate high quality fat-only abdominal images with high CNR
      and SNR in shorter scan duration than the conventional T1W TSE approach. As
      images generated by this sequence suffer from no flow artifacts, and are less
      sensitive to bulk, respiratory, and bowel motion, three-dimensional water
      saturated b-SSFP is a faster and more robust method for improving abdominal fat
      quantification using MRI.

PMID- 15723373
TI  - The mechanism of ring enhancement in hepatocellular carcinoma on
      superparamagnetic iron oxide-enhanced T1-weighted images: an investigation into
      peritumoral Kupffer cells.
AB  - PURPOSE: To investigate the mechanism of ring enhancement on ferumoxides-enhanced
      T1-weighted (T1W) gradient echo images in malignant focal hepatic lesions.
      MATERIALS AND METHODS: Eighteen patients with hepatocellular carcinoma (HCC)
      underwent breath-hold T1-, T2-, and T2*-weighted magnetic resonance (MR) images
      at 1.5-Tesla after ferumoxides administration. The existence of ring enhancement
      on T1W, and the maximum size of the area showing decreased phagocytic activity on
      T2W and T2*W, and that of the area showing ring enhancement on T1W were
      evaluated. The Kupffer cell (KC) density of HCC itself and peritumoral liver
      parenchyma was assessed with KC stain sections. RESULTS: Ring enhancement was
      noted in 13 of 18 HCC (72%). Peritumoral KC density was increased in the ring
      enhancement (+) group as compared with the ring enhancement (-) group. In the
      ring enhancement (+) group, the tumor size measured on T2W was smaller than that
      measured on either T1W or T2*W, suggesting a sustained T1 relaxation effect and a
      decreased T2* relaxation effect in the peritumoral regions. CONCLUSION: Ring
      enhancement on superparamagnetic iron oxide (SPIO)-enhanced T1W may correlate
      with increased KC density and decreased SPIO clustering in KC in peritumoral
      regions.

PMID- 15723374
TI  - Preoperative evaluation of intraductal papillary mucinous tumors performed by
      pancreatic magnetic resonance imaging and correlated with surgical and
      histopathologic findings.
AB  - PURPOSE: To evaluate the effectiveness of magnetic resonance imaging (MRI) in
      predicting the location, type of ductal involvement, and malignant transformation
      of intraductal papillary mucinous (IPM) pancreatic tumors made in a preoperative
      routine exam. MATERIALS AND METHODS: A total of 24 patients with histologic
      confirmation of IPM tumor (IPMT) were included in this study. The MR images
      obtained in operation patients were retrospectively assessed. Two radiologists
      who were unaware of the initial interpretations of the images independently
      analyzed the MRI studies and characterized the type of lesions, location, and
      signs of malignant transformation. Interobserver agreement was determined with
      weighted kappa statistics. After consensus of both radiologists, the observer
      performances for the MRI interpretations were compared with surgical and
      histologic results using weighted kappa statistics and Fisher test. RESULTS: At
      macroscopic examination, lesions were of combined type in 17 cases and of branch
      duct type in seven cases. At histologic analysis, three cases were classified as
      benign, three as borderline tumors, and 18 as carcinomas (eight in situ, 10
      invasive). The lesions were located mainly in the head or uncinate process (N =
      16) or were diffuse or multifocal (N = 2). Excellent agreement was found between
      the interpreters (0.90) in the evaluation of ductal involvement, good in the
      evaluation of lesion location (0.80) and in the diagnosis of malignant
      transformation (0.74). The correlation between MRI and histopathologic results
      was excellent in the evaluation of ductal involvement (0.90, sensitivity = 100%,
      specificity = 94%) and moderate in the evaluation of lesion location (0.57,
      sensitivity = 87%, specificity = 56%) and in the diagnosis of malignant
      transformation (0.60, sensitivity = 83%, specificity = 83%). CONCLUSION: MRI is
      an effective method of characterizing IPMT in preoperative practice. The
      predictive sign of IPM pancreatic tumor malignancy at MRI included only the
      presence of solid mass or mural nodules.

PMID- 15723375
TI  - Balloon sizing and transcatheter closure of acute atrial septal defects guided by
      magnetic resonance fluoroscopy: assessment and validation in a large animal
      model.
AB  - PURPOSE: To quantitatively assess atrial septal defects (ASDs) with small shunts
      using MRI followed by transcatheter closure monitored by MR fluoroscopy.
      MATERIALS AND METHODS: Acute ASDs were created in 14 pigs under x-ray
      fluoroscopy. Six animals were studied in order to select MR-compatible delivery
      systems and imaging strategies. ASDs in eight animals were examined with balloon
      sizing under MR fluoroscopy, flow measurements, and contrast media injections,
      after which transcatheter closure was performed under MR fluoroscopy. The
      delivery system was assembled from commercially available materials. RESULTS: The
      ratio of pulmonary to systemic flow (Qp/Qs) was reduced from 1.23 +/- 0.15 before
      ASD closure to 1.07 +/- 0.11 after ASD closure (P < 0.001). In two out of eight
      animals Qp/Qs was close to 1.0 before closure despite the presence of defects >15
      mm. The ASDs were measurable with MR balloon sizing in all of the animals.
      Balloon sizing was identical with MR (16.9 +/- 2.3 mm) and x-ray fluoroscopy
      (17.1 +/- 1.3 mm). The in-house-assembled delivery system allowed successful
      placement of closure devices under MR guidance. CONCLUSION: Assessment and
      closure of small shunts with MR fluoroscopy is feasible. A barrier to the rapid
      implementation of transcatheter closure in patients is uncertainty about the MR
      safety of guidewires and device delivery systems.

PMID- 15723376
TI  - Can a single-shot black-blood T2-weighted spin-echo echo-planar imaging sequence
      with sensitivity encoding replace the respiratory-triggered turbo spin-echo
      sequence for the liver? An optimization and feasibility study.
AB  - PURPOSE: To optimize and assess the feasibility of a single-shot black-blood T2
      weighted spin-echo echo-planar imaging (SSBB-EPI) sequence for MRI of the liver
      using sensitivity encoding (SENSE), and compare the results with those obtained
      with a T2-weighted turbo spin-echo (TSE) sequence. MATERIALS AND METHODS: Six
      volunteers and 16 patients were scanned at 1.5T (Philips Intera). In the
      volunteer study, we optimized the SSBB-EPI sequence by interactively changing the
      parameters (i.e., the resolution, echo time (TE), diffusion weighting with low b
      values, and polarity of the phase-encoding gradient) with regard to distortion,
      suppression of the blood signal, and sensitivity to motion. The influence of each
      change was assessed. The optimized SSBB-EPI sequence was applied in patients (N =
      16). A number of items, including the overall image quality (on a scale of 1-5),
      were used for graded evaluation. In addition, the signal-to-noise ratio (SNR) of
      the liver was calculated. Statistical analysis was carried out with the use of
      Wilcoxon's signed rank test for comparison of the SSBB-EPI and TSE sequences,
      with P = 0.05 considered the limit for significance. RESULTS: The SSBB-EPI
      sequence was improved by the following steps: 1) less frequency points than phase
      encoding steps, 2) a b-factor of 20, and 3) a reversed polarity of the phase
      encoding gradient. In patients, the mean overall image quality score for the
      optimized SSBB-EPI (3.5 (range: 1-4)) and TSE (3.6 (range: 3-4)), and the SNR of
      the liver on SSBB-EPI (mean +/- SD = 7.6 +/- 4.0) and TSE (8.9 +/- 4.6) were not
      significantly different (P > .05). CONCLUSION: Optimized SSBB-EPI with SENSE
      proved to be feasible in patients, and the overall image quality and SNR of the
      liver were comparable to those achieved with the standard respiratory-triggered
      T2-weighted TSE sequence.

PMID- 15723377
TI  - Real-time cine MRI of ventricular septal motion: a novel approach to assess
      ventricular coupling.
AB  - The purpose of this study was to assess the feasibility of magnetic resonance
      imaging (MRI) to evaluate in real-time, the effects of respiration in ventricular
      septal motion and configuration in normal volunteers and cardiac patients. Real
      time cine MRI studies, using the steady-state free precession (SSFP) technique,
      were performed in the cardiac short-axis during operator-guided deep inspiration
      and expiration in normal volunteers (N = 6), and in patients with constrictive
      pericarditis (CP; N = 6), restrictive cardiomyopathy (RCM; N = 4), chronic cor
      pulmonale (N = 5), and pericardial effusion. The respiratory effects on septal
      position and configuration during early ventricular filling were visually
      assessed. Results were compared with the short-axis breath-hold cine MRI studies,
      obtained at end-inspiration. In CP patients, onset of inspiration led to a
      leftward inversion in four of six patients and flattening of the septum in two of
      six patients during early ventricular filling. Septal abnormalities progressively
      disappeared during the following heartbeats. A similar pattern was found in one
      of six patients with pericardial effusion. The above pattern was absent in RCM
      patients. Although septal flattening during early inspiration was also found in
      two of six normal volunteers, flattening was minimal compared to that in CP
      patients. In all cor pulmonale patients, septal flattening or inversion was
      present, but this was not influenced by respiratory motion. Real-time cine MRI is
      a promising technique for determining the influence of respiration on septal
      motion and might be helpful in differentiating between different causes of
      impaired ventricular filling.

PMID- 15723378
TI  - Multislice MR first-pass myocardial perfusion imaging: impact of the receiver
      coil array.
AB  - PURPOSE: To compare a new 12-element body phased-array coil with a conventional
      four-element surface receiver coil array to provide increased signal-to-noise
      ratios (SNRs) for cardiac steady state free precession (SSFP) perfusion imaging.
      MATERIALS AND METHODS: Thirteen consecutive patients were included in the study.
      Patients were examined both with a four-element surface coil array and a 12
      element body coil array. First-pass myocardial perfusion imaging using saturation
      recovery SSFP was acquired during antecubital injection of Gd-DTPA. Imaging
      parameters: TR 2.8 msec/TE 1.3 msec, flip angle 50 degrees , bandwidth 960
      Hz/pixel and half-Fourier acquisition. SNR was calculated using six regions of
      interest (ROI) for the myocardial perfusion scans. Calculations of corresponding
      ROIs using the two different coil setups were compared using analysis of variance
      (ANOVA). Semiquantitative perfusion parameters were calculated for both groups.
      RESULTS: The mean SNR in myocardial perfusion imaging increased by 21% using the
      12-element coil setup (P < 0.001) when compared to the four-element coil. ROI
      comparisons revealed an increased signal inhomogeneity with the 12-element coil
      when compared to four-element coil experiments. Absolute normal range values of
      semiquantitative perfusion parameters were consistently higher using the 12
      element coil setup (P < 0.001). CONCLUSION: The 12-element coil array provides
      higher SNR, but these improvements come with trade-offs in image homogeneity.
      Increased SNR translates into higher semiquantitative perfusion values and offers
      the potential for improved detection of perfusion defects.

PMID- 15723379
TI  - Differentiation of noncancerous tissue and cancer lesions by apparent diffusion
      coefficient values in transition and peripheral zones of the prostate.
AB  - PURPOSE: To compare the apparent diffusion coefficient (ADC) values of prostate
      cancer in both the peripheral zone (PZ) and the transition zone (TZ) with those
      of benign tissue in the same zone using echo-planar diffusion weighted imaging
      with a parallel imaging technique. MATERIALS AND METHODS: A total of 29
      consecutive male patients (mean age 61.3 years, age range 53-88 years) with
      suspected prostate cancer were referred for MR imaging. All patients underwent
      transrectal ultrasound (TRUS)-guided biopsy of the prostate after MR imaging at
      1.5 T, including ADC. For each patient, seven to 10 specimens were obtained from
      the prostate, and regions of interest (ROIs) were drawn on the ADC map by
      referring to the urologist's illustration of TRUS-guided biopsy sites. ADC values
      of cancerous tissue in both the PZ and TZ were compared to those of noncancerous
      tissue in the same zone. RESULTS: Out of 29 patients, 23 had cancer tissue. In
      the 23 patients with cancer, the mean ADC value of all cancer ROIs and that of
      all noncancer ROIs, respectively, were 1.11 +/- 0.41 x 10(-3) and 1.68 +/- 0.40 x
      10(-3) mm(2)/second (values are mean +/- SD) (P < 0.01). The mean ADC value of TZ
      cancer ROIs and that of TZ noncancer ROIs, respectively, were 1.13 +/- 0.42 x 10(
      3) and 1.58 +/- 0.37 x 10(-3) mm(2)/second (P < 0.01). CONCLUSIONS: ADC
      measurement with a parallel imaging technique showed that ADC values of prostate
      cancer in both the PZ and TZ were significantly lower than those of benign tissue
      in the PZ and TZ, respectively.

PMID- 15723380
TI  - Continuous arterial spin labeling using a train of adiabatic inversion pulses.
AB  - PURPOSE: To develop a simple and robust magnetic resonance imaging (MRI) pulse
      sequence for the quantitative measurement of blood flow in the brain and cerebral
      tumors that has practical implementation advantages over currently used
      continuous arterial spin labeling (CASL) schemes. MATERIALS AND METHODS:
      Presented here is a single-coil protocol that uses a train of hyperbolic secant
      inversion pulses to produce continuous arterial spin inversion for perfusion
      weighting of fast spin echo images. Flow maps of normal rat brains and those
      containing a 9L gliosarcoma orthotopic tumor model conditions were acquired with
      and without carbogen. RESULTS: The perfusion-weighted images have reduced
      magnetization transfer signal degradation as compared to the traditional single
      coil CASL while avoiding the use of a more complex two-coil CASL technique. Blood
      flow measurements in tumor and normal brain tissue were consistent with those
      previously reported by other CASL techniques. Contralateral and normal brain
      showed increased blood flow with carbogen breathing, while tumor tissue lacked
      the same CO(2) reactivity. CONCLUSION: This variation of the CASL technique is a
      quantitative, robust, and practical single-coil method for measuring blood flow.
      This CASL method does not require specialized radiofrequency coils or amplifiers
      that are not routinely used for anatomic imaging of the brain, therefore allowing
      these flow measurements to be easily incorporated into traditional rodent
      neuroimaging protocols.

PMID- 15723381
TI  - Comparison of relative forced expiratory volume of one second with dynamic
      magnetic resonance imaging parameters in healthy subjects and patients with lung
      cancer.
AB  - PURPOSE: To assess relative forced expiratory volume in one second (FEV1/vital
      capacity (VC)) in healthy subjects and patients with a lung tumor using dynamic
      magnetic resonance imaging (dMRI) parameters. MATERIALS AND METHODS: In 15
      healthy volunteers and 31 patients with a non-small-cell lung carcinoma stage I
      (NSCLC I), diaphragmatic length change (LE1) and craniocaudal (CC) intrathoracic
      distance change within one second from maximal inspiration (DE1) were divided by
      total length change (LE(total), DE(total)) as a surrogate of spirometric FEV1/VC
      using a true fast imaging with steady-state precession (trueFISP) sequence (TE/TR
      = 1.7/37.3 msec, temporal resolution = 3 images/second). Influence of tumor
      localization was examined. RESULTS: In healthy volunteers FEV1/VC showed a highly
      significant correlation with LE1/LE(total) and DE1/DE(total) (r > 0.9, P < 0.01).
      In stage IB tumor patients, comparing tumor-bearing with the non-tumor-bearing
      hemithorax, there was a significant difference in tumors of the middle
      (LE1/LE(total) = 0.63 +/- 0.05 vs. 0.73 +/- 0.04, DE1/DE(total) = 0.66 +/- 0.05
      vs. 0.72 +/- 0.04; P < 0.05) and lower (P < 0.05) lung region. Stage IA tumor
      patients showed no significant differences with regard to healthy subjects.
      CONCLUSION: dMRI is a simple noninvasive method to locally determine
      LE1/LE(total) and DE1/DE(total) as a surrogate of FEV1/VC in volunteers and
      patients. Tumors of the middle and lower lung regions have a significant
      influence on these MRI parameters.

PMID- 15723382
TI  - Effect of free radical scavenger (tempol) on intrarenal oxygenation in
      hypertensive rats as evaluated by BOLD MRI.
AB  - PURPOSE: To demonstrate a differential response following administration of a
      free radical scavenger, tempol, in kidneys of hypertensive compared to
      normotensive rats. MATERIAL AND METHODS: Data were obtained in spontaneously
      hypertensive rats (SHR, N = 5). Wistar-Kyoto rats (WKY, N = 6) were used as
      normotensive controls. RESULTS: Consistent with prior reports, SHRs show a
      significant response to tempol (R(2)*decreased from 40.56 +/- 0.66 second(-1) to
      28.58 +/- 0.6 second(-1) in medulla, P < 0.05), while WKY rats exhibit a minimal
      change (R(2)* measuring 22.36 +/- 4.38 second(-1) pre-tempol and 21.57 +/- 4.78
      second(-1) post-tempol, in medulla). The post-tempol R(2)* in SHR was found to be
      comparable to pre-tempol values in WKY rats, suggesting an improved medullary
      oxygenation in SHRs. CONCLUSION: Based on both baseline R(2)* values and the
      differential effect of the free radical scavenger on renal medullary oxygenation,
      BOLD MRI can distinguish hypertensive from normal kidney in rats.

PMID- 15723383
TI  - Cyclopentenone prostaglandins PGA2 and 15-deoxy-delta12,14 PGJ2 suppress
      activation of murine microglia and astrocytes: implications for multiple
      sclerosis.
AB  - The cyclopentenone prostaglandin (cPG) 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2))
      has been identified as a potent antiinflammatory agent that is able to inhibit
      the activation of macrophages and microglia. Additionally, 15d-PGJ(2) is able to
      ameliorate the clinical manifestations of experimental autoimmune
      encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Many
      biological effects of 15d-PGJ(2) have been attributed to the peroxisome
      proliferator activated receptor-gamma (PPAR-gamma). PGA(2), like 15d-PGJ(2), is a
      cPG. The aim of this study is to compare the relative effectiveness of these two
      cPGs in inhibiting the inflammatory response of mouse microglia and astrocytes,
      two cell types that upon activation may contribute to the pathology of EAE and
      MS. Purified primary mouse microglia and astrocytes were treated with either 15d
      PGJ(2) or PGA(2) and then stimulated with either lipopolysaccharide (LPS) or a
      combination of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. The
      results show that 15d-PGJ(2) and PGA(2) both potently inhibited the production of
      nitrite, as well as proinflammatory cytokines and chemokines, from microglia and
      astrocytes. Generally, regulation of NO production was more sensitive to 15d
      PGJ(2), however, cytokine and chemokine production was more sensitive to PGA(2)
      treatment. These results demonstrate for the first time that PGA(2) is a potent
      antiinflammatory mediator.

PMID- 15723384
TI  - Pharmacotherapy of adult ADHD.
AB  - Although attention deficit hyperactivity disorder (ADHD) has been officially
      recognized as persisting into adulthood for more than 25 years, only recently has
      the condition been studied in adults. There is great syndromatic continuity
      between childhood and adult ADHD, and thus much of the medication management of
      adults with ADHD can be based on the experience gained from treating children and
      adolescents. Stimulant medications remain the treatment of choice and are
      generally as effective in adults as they are in children. Several extended
      release delivery systems that improve convenience and compliance have become
      available. Several second-line medications are also reviewed. The medications
      must be fine-tuned to the needs of the individual patient in regard to the dose
      and timing of dose that achieve optimal therapeutic benefit. Medication
      adjustment must be done by trial and error because no parameter yet identified
      predicts the molecule or dose that will provide optimal performance.

PMID- 15723385
TI  - Extraction of overt verbal response from the acoustic noise in a functional
      magnetic resonance imaging scan by use of segmented active noise cancellation.
AB  - A method to extract the subject's overt verbal response from the obscuring
      acoustic noise in an fMRI scan is developed by applying active noise cancellation
      with a conventional MRI microphone. Since the EPI scanning and its accompanying
      acoustic noise in fMRI are repetitive, the acoustic noise in one time segment was
      used as a reference noise in suppressing the acoustic noise in subsequent
      segments. However, the acoustic noise from the scanner was affected by the
      subject's movements, so the reference noise was adaptively adjusted as the
      scanner's acoustic properties varied in time. This method was successfully
      applied to a cognitive fMRI experiment with overt verbal responses.

PMID- 15723386
TI  - Changes in N-linked sugar chain patterns induced by moderate-to-high expression
      of the galactosyltransferase I gene in a brain-derived cell line, CG4.
AB  - Oligosaccharides with biantennae and bisecting N-acetyl glucosamine (GlcNAc)
      residues attached to the mannose in the beta1-4 trimannosyl core (BA2) are
      enriched in the brain and considered brain-type sugar chains. We investigated the
      significance of the interplay between galactosyltransferase I (GalTase I) and BA2
      formation in a brain-derived cell line, CG4. Increased GalTase expression in
      different glial- and neuronal-derived cell lines was accompanied by decreased or
      undetectable levels of BA2, depending on the level of GalTase expression.
      Forceful expression of GalTase I in CG4 cells expressing high levels of BA2 and
      low GalTase activity significantly reduced BA2 levels. In addition, a sixfold
      increase in an abnormal sugar chain A1(6)G1Fo and a moderate increase in
      A2G2Fo(6)F were evident. The increased levels of A1(6)G1Fo indicate a diversion
      or abrogation of the N-linked sugar chain biosynthetic pathway from normal. The
      accumulation of A1(6)G1Fo and increased A2G2Fo(6)F levels were accompanied by
      decreased levels of the high mannose-type sugar chains, M5A, M6B, M8A, and M9A.
      Increased GalTase I expression also led to stunted growth and abnormal morphology
      of CG4 cells, with increased mortality. Even moderate overexpression of GalTase I
      thus disrupts the normal biosynthetic pathway of N-linked sugar chains, and high
      overexpression is fatal to CG4 cells.

PMID- 15723387
TI  - Implementation issues of multivoxel STEAM-localized 1H spectroscopy.
AB  - Single-voxel STEAM-localized spectroscopy studies of neuropsychiatric patients
      yield high-quality data at short echo times, but are often limited to only a few
      regions of interest due to the linear increase of acquisition time with the
      number of regions examined. A multivoxel STEAM approach increases the number of
      regions of interest examined with a less than linear increase in acquisition
      time. Several implementation issues were considered, especially the signal
      contribution of outer voxel stimulated echoes (OVSE), which can lead to
      systematic errors in the quantification of relative metabolite concentrations.
      The relative signal contribution of OVSEs was found to be as great as 30% in
      phantoms. Gradient polarity switching completely canceled the contribution of
      OVSEs. A two-voxel STEAM approach produces phantom and in vivo data quality
      comparable to single-voxel STEAM in practically half the time. Quantification
      precision and accuracy are preserved in phantoms and in vivo.

PMID- 15723388
TI  - Time-resolved undersampled projection reconstruction magnetic resonance imaging
      of the peripheral vessels using multi-echo acquisition.
AB  - The hybrid projection reconstruction (PR) imaging provides high temporal
      resolution through an undersampled PR acquisition for the in-plane dimensions and
      Cartesian slice encoding for the through-plane dimension. The undersampling of
      projection data introduces streak artifact, which may severely compromise image
      quality. This study reports on a combination of multi-echo acquisition with time
      resolved undersampled PR imaging and its application to peripheral magnetic
      resonance angiography. Multi-echo acquisition improved imaging speed effectively,
      thereby reducing the undersampling streak artifact and improving the temporal
      resolution. The gradient distortion was reduced through gradient calibration and
      accurate k-space trajectory measurement.

PMID- 15723389
TI  - Gradual changes in the apparent diffusion coefficient of water in selectively
      vulnerable brain regions following brief ischemia in the gerbil.
AB  - Although selective vulnerability and delayed neuronal death following global
      ischemia have been recognized in both the human and animal brain, the underlying
      mechanisms of cell damage are not fully understood. In this study we investigated
      the time-dependent changes of the apparent diffusion coefficient (ADC) of water
      and cerebral blood flow (CBF) in a classic animal model of selective
      vulnerability and delayed neuronal death, using magnetic resonance (MR) diffusion
      and perfusion-weighted imaging. CBF was monitored using the noninvasive MR
      arterial spin labeling method called flow-sensitive alternating inversion
      recovery (FAIR). Bilateral common carotid occlusion was induced for 5 min,
      followed by 10 hr of reperfusion in a gerbil model. The most notable finding was
      that the lateral portion of the striatum in the basal ganglia exhibited a
      prolonged and gradual ADC decrease throughout the study following reperfusion.
      This pattern was not exhibited within the cortex. It is suggested that regions
      known to exhibit so-called delayed cell death progress to infarction via a
      gradual process that can be monitored by MR diffusion-weighted imaging (DWI).

PMID- 15723390
TI  - Interindividual reproducibility of glutamate quantification using 1.5-T proton
      magnetic resonance spectroscopy.
AB  - The goal of this study was to measure the interindividual reproducibility of
      glutamate quantification in 1.5-T (1)H MRS of human brains. To determine the
      effective echo time (TE) for glutamate quantification, spectra from a phantom and
      12 participants were obtained with TE = 30, 35, 40, and 144 ms (repetition time
      (TR) = 2000 ms and volume of interest = 4 cm(3)). The average Cramer-Rao lower
      bounds for glutamate quantification using LCModel was lowest in two experiments
      when TE = 40 ms.Twenty-one subjects participated in experiments that measured
      interindividual reproducibility of glutamate quantification. Spectra were
      acquired with TR = 6000 ms and TE = 40 ms. Results showed that the coefficients
      of variance were 11.0 and 13.1% in the anterior cingulate cortex and insula,
      respectively. This suggests that glutamate can be reproducibly measured from 1.5
      T (1)H MRS with long TR, effective TE, and the LCModel.

PMID- 15723391
TI  - Vessel size imaging in humans.
AB  - The relation of contrast-enhanced transverse relaxation rates R2* and R2 provides
      in vivo mapping of the mean caliber of cerebral vessels. This technique is
      referred to as vessel size imaging (VSI). Here a quantitative assessment of the
      vessel caliber in brain tumor patients is presented. The obtained mean vessel
      size shows sensitivity to the tumor type. A theoretical analysis is given to
      elucidate the morphological information content of VSI in the context of vessel
      architecture. The simplification of the theory underlying the data processing
      results in a systematic overestimation of the vessel caliber. An increase in the
      magnetic susceptibility of the contrast agent allows for quantitatively more
      accurate measurements. Quantitative VSI must include measurements of the regional
      diffusion coefficient and absolute determination of the regional cerebral blood
      volume.

PMID- 15723392
TI  - Theory of susceptibility-induced transverse relaxation in the capillary network
      in the diffusion narrowing regime.
AB  - The transverse relaxation effect of deoxyhemoglobin compartmentalization in
      erythrocytes in the capillary network is investigated using an analytical
      approach. The capillaries are modeled as long arrays of paramagnetic spheres,
      simulating the individual red blood cells. Calculations are performed in the
      diffusion narrowing regime, which holds for the native blood paramagnetism at
      moderate fields up to about 1.5 T, for the free induction decay, the Hahn spin
      echo, and the Carr-Purcell-Meiboom-Gill sequence. The commonly used model of
      capillaries as homogeneously magnetized cylinders is shown to underestimate the
      capillary contribution to the susceptibility-induced relaxation rate by up to
      55%. This results in a noticeable change in the predicted deoxyhemoglobin
      concentration needed to cause the variation in the transverse relaxation rate
      observed in functional MRI and may affect subsequent quantification of
      physiological parameters derived from the BOLD signal. Furthermore, the model for
      the individual red blood cells (RBCs) represents a framework for investigating
      the effects of interspecies and intersubject variations in hematocrit, RBC
      deoxyhemoglobin concentration, and cell size on the relaxation rate. The results
      agree within their validity domain with previous Monte Carlo simulations.

PMID- 15723393
TI  - Four-phase single-capillary stepwise model for kinetics in arterial spin labeling
      MRI.
AB  - An extended model for extracting measures of brain perfusion from pulsed arterial
      spin labeling (ASL) data while considering transit effects and restricted
      permeability of capillaries to blood water is proposed. We divided the time
      course of the signal difference between control and labeled images into four
      phases with respect to the arrival time of labeled blood water at the voxel of
      interest (t(A)), transit time through the arteries in the voxel (t(ex)), and
      duration of the bolus of labeled spins (tau). Dividing the labeled slab of blood
      water into many discrete segments, and adapting numerical integration methods
      allowed us to conveniently model restricted capillary-tissue exchange based on a
      modified distributed parameter model. We compared this four-phase single
      capillary stepwise (FPSCS) model with models that treat water as a freely
      diffusible tracer, using both simulations and experimental ASL brain imaging data
      at 1.5T from eight healthy subjects (24-80 years old). The FPSCS model yielded
      less errors in the least-squares sense in fitting brain ASL data in comparison
      with freely diffusible tracer models of water (P = 0.055). These results imply
      that restricted permeability of capillaries to water should be considered when
      brain ASL data are analyzed.

PMID- 15723394
TI  - Spatial characterization of T1 and T2 relaxation times and the water apparent
      diffusion coefficient in rabbit Achilles tendon subjected to tensile loading.
AB  - Tendons exhibit viscoelastic mechanical behavior under tensile loading. The
      elasticity arises from the collagen chains that form fibrils, while the viscous
      response arises from the interaction of the water with the solid matrix.
      Therefore, an understanding of the behavior of water in response to the
      application of a load is crucial to the understanding of the origin of the
      viscous response. Three-dimensional MRI mapping of rabbit Achilles tendons was
      performed at 2.0 T to characterize the response of T(1) and T(2) relaxation times
      and the apparent diffusion coefficient (ADC) of water to tensile loading. The ADC
      was measured in directions both parallel (ADC( parallel)) and perpendicular (ADC(
      perpendicular)) to the long axis of the tendon. At a short diffusion time (5.8
      ms) MR parameter maps showed the existence of two regions, here termed "core" and
      "rim", that exhibited statistically significant differences in T(1), T(2), and
      ADC( perpendicular) under the baseline loading condition. MR parameter maps were
      also generated at a second loading condition of approximately 1 MPa. At a
      diffusion time of 5.8 ms, there was a statistically significant increase in the
      rim region for both ADC( perpendicular) (57.5%) and ADC( parallel) (20.5%) upon
      tensile loading. The changes in core ADC(( perpendicular), ( parallel)), as well
      as the relaxation parameters in both core and rim regions, were not statistically
      significant. The effect of diffusion time on the ADC(( perpendicular), (
      parallel)) values was investigated by creating maps at three additional diffusion
      times (50.0, 125.0, 250.0 ms) using a diffusion-weighted, stimulated-echo (DW
      STE) pulse sequence. At longer diffusion times, ADC(( perpendicular), (
      parallel)) values increased rather than approaching a constant value. This
      observation was attributed to T(1) spin-editing during the DW-STE pulse sequence,
      which resulted in the loss of short-T(1) components (with correspondingly lower
      ADCs) at longer diffusion times (corroborating the results from earlier
      spectroscopic work). The T(1) spin-editing effect was observed both in the core
      and in the rim regions of the tendon and hence was not solely due to the
      redistribution of water from the core to the rim upon loading. A measure
      reflective of the regional change in proton density was noted to be consistent
      with tensile-load-induced water transport from the central to the peripheral
      tendon region.

PMID- 15723395
TI  - Advantages of frequency-domain modeling in dynamic-susceptibility contrast
      magnetic resonance cerebral blood flow quantification.
AB  - In dynamic-susceptibility contrast magnetic resonance perfusion imaging, the
      cerebral blood flow (CBF) is estimated from the tissue residue function obtained
      through deconvolution of the contrast concentration functions. However, the
      reliability of CBF estimates obtained by deconvolution is sensitive to various
      distortions including high-frequency noise amplification. The frequency-domain
      Fourier transform-based and the time-domain singular-value decomposition-based
      (SVD) algorithms both have biases introduced into their CBF estimates when noise
      stability criteria are applied or when contrast recirculation is present. The
      recovery of the desired signal components from amid these distortions by modeling
      the residue function in the frequency domain is demonstrated. The basic
      advantages and applicability of the frequency-domain modeling concept are
      explored through a simple frequency-domain Lorentzian model (FDLM); with results
      compared to standard SVD-based approaches. The performance of the FDLM method is
      model dependent, well representing residue functions in the exponential family
      while less accurately representing other functions.

PMID- 15723396
TI  - Localized two-dimensional 1H magnetic resonance exchange spectroscopy: a
      preliminary evaluation in human muscle.
AB  - A localized two-dimensional (2D) (1)H MR chemical exchange spectroscopic (L-EXSY)
      sequence has been implemented on a whole-body 1.5-T MRI/MRS scanner. The second
      spectroscopic encoding to monitor the chemical exchange was an integral part of
      the single-volume localization using three slice-selective 90 degrees
      radiofrequency (RF) pulses, thereby eliminating the need for any additional RF
      pulses, off-resonance/continuous wave saturation, or selective inversion, which
      are essential in the one-dimensional (1)H MR exchange spectroscopy. Even though
      the TM-crusher dephased single- and higher-order multiple-quantum coherences, the
      zero-quantum coherences were indistinguishable from the longitudinal
      magnetization leading to J-coupled 2D cross peaks similar to COSY. With TM of 300
      ms, two different exchange cross peaks were recorded in human calf muscle: a
      first peak, between the mobile tissue water and total creatine pools, and a
      second peak, possibly between the olefinic and magnetically equivalent poly
      methylene protons of unsaturated lipids. Our preliminary results demonstrate that
      the intermolecular and intramolecular chemical exchange mechanisms can be
      monitored noninvasively in human calf muscle using 2D L-EXSY.

PMID- 15723398
TI  - k-space undersampling in PROPELLER imaging.
AB  - PROPELLER MRI (periodically rotated overlapping parallel lines with enhanced
      reconstruction) provides images with significantly fewer B(0)-related artifacts
      than echo-planar imaging (EPI), as well as reduced sensitivity to motion compared
      to conventional multiple-shot fast spin-echo (FSE). However, the minimum imaging
      time in PROPELLER is markedly longer than in EPI and 50% longer than in
      conventional multiple-shot FSE. Often in MRI, imaging time is reduced by
      undersampling k-space. In the present study, the effects of undersampling on
      PROPELLER images were evaluated using simulated and in vivo data sets.
      Undersampling using PROPELLER patterns with reduced number of samples per line,
      number of lines per blade, or number of blades per acquisition, while maintaining
      the same k-space field of view (FOV(k)) and uniform sampling at the edges of
      FOV(k), reduced imaging time but led to severe image artifacts. In contrast,
      undersampling by means of removing whole blades from a PROPELLER sampling pattern
      that sufficiently samples k-space produced only minimal image artifacts, mainly
      manifested as blurring in directions parallel to the blades removed, even when
      reducing imaging time by as much as 50%. Finally, undersampling using asymmetric
      blades and taking advantage of Hermitian symmetries to fill-in the missing data
      significantly reduced imaging time without causing image artifacts.

PMID- 15723397
TI  - In vivo method for correcting transmit/receive nonuniformities with phased array
      coils.
AB  - Phased array coils are finding widespread applications in both the research and
      the clinical setting. However, intensity nonuniformities with such coils can
      reduce the potential benefits of these coils, particularly for applications such
      as tissue segmentation. In this work, a method is described for correcting the
      nonuniform signal response based on in vivo measures of both the transmission
      field of body coil and the reception sensitivity of phased array coils,
      separately. For a uniform phantom, the reception sensitivity can be calculated
      using both Bloch equations and transmission field maps. For a heterogeneous
      object such as a brain, a minimal contrast acquisition must be obtained to map
      the receiver nonuniformities. This transmit field/receiver sensitivity (TFRS)
      approach is compared with the standard methods of using the body coil to obtain a
      reference scan and low-pass filtering. The quantitative comparison results shows
      that the TFRS approach provides superior results in correcting intensity
      nonuniformities for a uniform phantom. This approach reduces the ratio between
      signal intensity SD of an image and its mean intensity from approximately 21%
      before correction to 13% after correction. Results are also shown demonstrating
      the utility of this approach in vivo with human brain images. The method is
      general and can be applied with most pulse sequences, any coil combination for
      transmission and reception, and in any anatomic region.

PMID- 15723399
TI  - Sodium magnetic resonance imaging of diuresis: spatial and kinetic response.
AB  - Renal function is highly correlated with the sodium concentration gradient along
      the corticomedullary axis. The application of 3D high-resolution sodium magnetic
      resonance imaging (MRI) provided a means to quantify in vivo the spatial and
      temporal changes in renal tissue sodium concentration under normal and diuretic
      conditions. A detailed, pixel-by-pixel analysis of the intact rat kidney sodium
      MR images yielded a quantitative measure of the corticomedullary sodium gradient
      before and at early and later times after the administration of two distinct
      diuretic agents, furosemide and mannitol. Furosemide, a loop diuretic, induced a
      fivefold reduction in the cortical-outer medullary sodium gradient, whereas
      mannitol, an osmotic diuretic, did not affect this gradient. Both diuretics
      induced a 50% decrease in the sodium concentration of the inner medulla; however,
      mannitol exerted its effect twice as fast as furosemide with a 2.5-min
      exponential decay constant. These specific changes were attributed to the
      different mechanism of action and site of activity of each diuretic agent. Thus,
      high-resolution (23)Na MRI offers a unique, noninvasive tool for functional
      imaging of the kidney physiology.

PMID- 15723400
TI  - Manganese-enhanced magnetic resonance imaging of mouse brain after systemic
      administration of MnCl2: dose-dependent and temporal evolution of T1 contrast.
AB  - Manganese is a useful contrast agent for MRI of animals. Previously, it has been
      shown that systemic doses of MnCl(2) provide unique contrast in the rodent brain,
      enabling visualization of neuroarchitecture. The present work investigates the
      dose and temporal dependence of brain enhancement after i.v. administration of
      MnCl(2). Varying doses of MnCl(2) (9-175 mg/kg) were administered to mice from 0
      to 24 h prior to T(1)-weighted manganese-enhanced MRI (MEMRI) at 11.7 T. Pre
      MnCl(2) T(1) values measured in different brain regions ranged from 1.17 +/- 0.03
      to 1.76 +/- 0.01 s. Post-MnCl(2) T(1) measured 24 hr after administration of
      MnCl(2) were significantly decreased, even after the lowest dose of MnCl(2). The
      largest decreases occurred in the pituitary gland, where post-MnCl(2) T(1) ranged
      from 231 +/- 23 ms following the lowest dose to 143 +/- 43 ms after the highest
      dose, while the smallest decreases were observed in cortex (post-MnCl(2) T(1) =
      1060 +/- 5 ms for low dose and 637 +/- 5 ms for high dose). The contrast
      resulting after 14 hr did not change up to 24 hr. Enhancement first occurred in
      subarachnoid spaces, followed by ventricles and periventricular tissues, and
      finally reached the remainder of the brain. Cortical layers were detected at
      higher doses (>88 mg/kg) and olfactory bulb layers were detected with the lowest
      dose (9 mg/kg). Temporal evolution of the enhancement of the olfactory bulb
      layers was observed. In some regions of the brain, such as hippocampus and
      thalamus, the changes in contrast detected between 2 and 14 hr used very specific
      pathways. These results demonstrate that both the dose and the time after MnCl(2)
      can be manipulated to optimize brain contrast in a region-specific manner.

PMID- 15723401
TI  - Free breathing 3D balanced FFE coronary magnetic resonance angiography with
      prolonged cardiac acquisition windows and intra-RR motion correction.
AB  - A shortcoming of today's coronary magnetic resonance angiography (MRA) is its low
      total scan efficiency (<5%), as only small well-defined fractions of the
      respiratory (50%) and cardiac (10%) cycle are used for data acquisition. These
      precautions are necessary to prevent blurring and artifacts related to
      respiratory and cardiac motion. Hence, scan times range from 4 to 9 min, which
      may not be tolerated by patients. To overcome this drawback, an ECG-triggered,
      navigator-gated free breathing radial 3D balanced FFE sequence with intra-RR
      motion correction is investigated in this study. Scan efficiency is increased by
      using a long cardiac acquisition window during the RR interval. This allows the
      acquisition of a number of independent k-space segments during each cardiac
      cycle. The intersegment motion is corrected using a self-guided epicardial fat
      tracking procedure in a postprocessing step. Finally, combining the motion
      corrected segments forms a high-resolution image. Experiments on healthy
      volunteers are presented to show the basic feasibility of this approach.

PMID- 15723402
TI  - Shutter-speed analysis of contrast reagent bolus-tracking data: Preliminary
      observations in benign and malignant breast disease.
AB  - The standard pharmacokinetic model applied to contrast reagent (CR) bolus
      tracking (B-T) MRI (dynamic-contrast-enhanced) data makes the intrinsic
      assumption that equilibrium transcytolemmal water molecule exchange is
      effectively infinitely fast. Theory and simulation have suggested that this
      assumption can lead to significant errors. Recent analyses of animal model
      experimental data have confirmed two predicted signature inadequacies: a specific
      temporal mismatch with the B-T time-course and a CR dose-dependent
      underestimation of model parameters. The most parsimonious adjustment to account
      for this aspect leads to the "shutter-speed" pharmacokinetic model. Application
      of the latter to the animal model data mostly eliminates the two signature
      inadequacies. Here, the standard and shutter-speed models are applied to B-T data
      obtained from routine human breast examinations. The signature standard model
      temporal mismatch is found for each of the three invasive ductal carcinoma (IDC)
      cases and for each of the three fibroadenoma (FA) cases studied. It is
      effectively eliminated by use of the shutter-speed model. The size of the
      mismatch is considerably greater for the IDC lesions than for the FA lesions,
      causing the shutter-speed model to exhibit improved discrimination of malignant
      IDC tumors from the benign FA lesions compared with the standard model.
      Furthermore, the shutter-speed model clearly reveals focal "hot spots" of
      elevated CR perfusion/permeation present in only the malignant tumors.

PMID- 15723403
TI  - Macroscopic orientation component analysis of brain white matter and thalamus
      based on diffusion tensor imaging.
AB  - Diffusion tensor imaging (DTI) can delineate white matter architecture based on
      fiber orientation. The purpose of this paper is to use the orientation
      information contained in DTI to study axonal organization of the brain both
      macroscopically and quantitatively. After performing gray/white matter
      segmentation using a fractional anisotropy threshold, the white matter can be
      further decomposed into components composed of tracts oriented along three
      orthogonal anatomic axes (right-left, superior-inferior, and anterior-posterior).
      For each component, the volume and MR parameters were quantified. To characterize
      the axonal architecture of the brain, this technique was applied to the entire
      brain using a Talairach-based brain parcellation method and to the thalamus by
      manual segmentation. Reproducibility of this analysis tool was examined by
      repeating the measurements in the same subject, and individual differences were
      appreciated from the data acquired in 11 healthy volunteers. Based on the results
      from these preliminary data sets, this new analysis technique is expected to be
      an effective tool for macroscopic white matter characterization.

PMID- 15723404
TI  - Controlled aliasing in parallel imaging results in higher acceleration
      (CAIPIRINHA) for multi-slice imaging.
AB  - In all current parallel imaging techniques, aliasing artifacts resulting from an
      undersampled acquisition are removed by means of a specialized image
      reconstruction algorithm. In this study a new approach termed "controlled
      aliasing in parallel imaging results in higher acceleration" (CAIPIRINHA) is
      presented. This technique modifies the appearance of aliasing artifacts during
      the acquisition to improve the subsequent parallel image reconstruction
      procedure. This new parallel multi-slice technique is more efficient compared to
      other multi-slice parallel imaging concepts that use only a pure postprocessing
      approach. In this new approach, multiple slices of arbitrary thickness and
      distance are excited simultaneously with the use of multi-band radiofrequency
      (RF) pulses similar to Hadamard pulses. These data are then undersampled,
      yielding superimposed slices that appear shifted with respect to each other. The
      shift of the aliased slices is controlled by modulating the phase of the
      individual slices in the multi-band excitation pulse from echo to echo. We show
      that the reconstruction quality of the aliased slices is better using this shift.
      This may potentially allow one to use higher acceleration factors than are used
      in techniques without this excitation scheme. Additionally, slices that have
      essentially the same coil sensitivity profiles can be separated with this
      technique.

PMID- 15723405
TI  - Molecular MR imaging of melanoma angiogenesis with alphanubeta3-targeted
      paramagnetic nanoparticles.
AB  - Neovascularization is a critical component in the progression of malignant
      melanoma. The objective of this study was to determine whether alpha(nu)beta(3)
      targeted paramagnetic nanoparticles can detect and characterize sparse
      alpha(nu)beta integrin expression on neovasculature induced by nascent melanoma
      xenografts ( approximately 30 mm(3)) at 1.5T. Athymic nude mice bearing human
      melanoma tumors were intravenously injected with alpha(v)beta(3)-integrin
      targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or
      alpha(v)beta(3)-targeted-nonparamagnetic nanoparticles 2 hr before they were
      injected with alpha(v)beta(3)-integrin-targeted paramagnetic nanoparticles (i.e.,
      in vivo competitive blockade) and imaged with MRI. Contrast enhancement of
      neovascularity in animals that received alpha(nu)beta(3)-targeted paramagnetic
      nanoparticles increased 173% by 120 min. Signal contrast with nontargeted
      paramagnetic nanoparticles was approximately 50% less than that in the targeted
      group (P < 0.05). Molecular MRI results were corroborated by histology. In a
      competitive cell adhesion assay, incubation of alpha(nu)beta(3)-expressing cells
      with targeted nanoparticles significantly inhibited binding to a vitronectin
      coated surface, confirming the bioactivity of the targeted nanoparticles. The
      present study lowers the limit previously reported for detecting sparse
      biomarkers with molecular MRI in vivo. This technique may be employed to
      noninvasively detect very small regions of angiogenesis associated with nascent
      melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.

PMID- 15723406
TI  - Mechanical transient-based magnetic resonance elastography.
AB  - Magnetic resonance elastography (MRE) is a technique for quantifying material
      properties by measuring cyclic displacements of propagating shear waves. As an
      alternative to dynamic harmonic wave MRE or quasi-steady-state methods, the idea
      of using a transient impulse for mechanical excitation is introduced. Two
      processing methods to calculate shear stiffness from transient data were
      developed. The techniques were tested in phantom studies, and the transient
      results were found to be comparable to the harmonic wave results. Transient wave
      based analysis was applied to the brains of six healthy volunteers in order to
      assess the method in areas of complex wave patterns and geometry. The results
      demonstrated the feasibility of measuring brain stiffness in vivo using a
      transient mechanical excitation. Transient and harmonic methods both measure
      white matter (approximately 12 kPa) to be stiffer than gray matter (
      approximately 8 kPa). There were some anatomic differences between harmonic and
      transient MRE, specifically where the transient results better depicted the
      deeper structures of the brain.

PMID- 15723407
TI  - Myocardial blood flow mapping in mice using high-resolution spin labeling
      magnetic resonance imaging: influence of ketamine/xylazine and isoflurane
      anesthesia.
AB  - Genetically modified mouse models of many human diseases reflecting
      cardiovascular alterations are currently available. To date, little information
      on absolute myocardial perfusion in mice is found in the literature. High
      resolution quantitative myocardial blood flow maps (in-plane resolution 156 x 312
      mum(2), slice thickness 1.5 mm) have been obtained noninvasively within 25 min at
      4.7 T in 30 freely breathing C57/Bl6J mice using electrocardiogram- and
      respiration-gated spin labeling magnetic resonance imaging (MRI). Regional
      myocardial blood flow measurements were carried out, and the effects of
      isoflurane at two different concentrations and ketamine/xylazine anesthesia were
      assessed. The mean blood flow value in the left ventricular myocardium was 6.0 +/
      1.9 mL g(-1) min(-1) under ketamine/xylazine and 6.9 +/- 1.7 mL g(-1) min(-1)
      (group average +/- SD) under isoflurane (1.25%). Under the influence of higher
      isoflurane concentration (2.00%), myocardial blood flow increased dramatically to
      16.9 +/- 1.8 mL g(-1)min(-1) with no significant change in heart rate. This work
      illustrates the feasibility of noninvasive quantitative myocardial perfusion
      mapping in mice using MRI. The study of the influence of anesthesia shows that
      myocardial blood flow is highly sensitive to isoflurane concentration. The method
      employed offers a noninvasive approach to longitudinal studies of murine models
      of cardiac disease.

PMID- 15723408
TI  - MR imaging of biodegradable polymeric microparticles: a potential method of
      monitoring local drug delivery.
AB  - Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was encapsulated into
      biodegradable, bioadhesive polymeric microparticles to enable noninvasive
      monitoring of their local intravesical delivery with MRI. The microparticles were
      characterized by contrast agent encapsulation and release kinetics, T(1)
      relaxation rates, and contrast enhancement in vivo. The level of Gd-DTPA loading
      into microparticles was 14.3 +/- 0.6 mug/mg polymer. The measured T(1) relaxation
      rates of the microparticles showed a direct dependence on Gd-DPTA content. Both
      1.5T and 4.7T MR scanners were used to image murine bladders instilled
      intravesically with Gd-DTPA-loaded particles in vivo. MR images showed ring
      shaped regions of enhancement inscribing the bladder wall, which were attributed
      to the microparticles that were preferentially adherent to the mucosa lining the
      urothelium. The images of controls exhibited no such enhancement. The normalized
      signal intensities measured from post-instillation images were significantly
      greater (P < 0.05) than those in the pre-instillation images. Contrast
      enhancement was observed for at least 5 days after the initial instillation,
      although the enhancement decreased due to microparticle degradation or mucosa
      renewal. The localized distribution of biodegradable, bioadhesive microparticles
      encapsulating Gd-DTPA was successfully visualized with MRI in vivo, allowing
      particle-mediated delivery to be temporally and spatially monitored
      noninvasively.

PMID- 15723409
TI  - 129Xe spectra from the heads of rats with and without ligation of the external
      carotid and pterygopalatine arteries.
AB  - After rats inhaled hyperpolarized (129)Xe gas, in vivo spectra from their heads
      revealed a dominant peak around 195 ppm, another easily resolvable peak near 189
      ppm, a broad peak around 210 ppm, and two minor peaks around 198 ppm and 192 ppm.
      However, the source of each peak remains controversial. To further study the
      origin of each peak, we compared spectra obtained from the heads of normal rats
      with spectra taken from the heads of rats that had undergone ligation of the
      external carotid (ECA) and pterygopalatine (PPA) arteries, the major feeding
      vessels of nonbrain tissue in the rat head. The amplitude of the peak at around
      189 ppm was greatly reduced in the ECA/PPA-ligated rats, while the peak around
      195 ppm persisted. We conclude that the signal that originates from the rat brain
      after inhalation of (129)Xe gas is overwhelmingly dominated by the single
      resonance at 195 ppm.

PMID- 15723410
TI  - Oxygen-sensitive contrast in blood for steady-state free precession imaging.
AB  - Steady-state free precession (SSFP) methods have gained widespread recognition
      for their ability to provide fast scans at high signal-to-noise ratio. This paper
      demonstrates that such methods are also capable of reflecting functional
      information, particularly blood oxygenation state. It is well known that SSFP
      signals show substantial sensitivity to small off-resonance frequency variations.
      However, that mechanism cannot explain the oxygen-sensitive contrast in blood
      that was observed with steady-state methods using phase-cycled radiofrequency
      pulses. From theoretical and experimental models it is demonstrated that the
      mechanism responsible for such contrast originates from the motion of spins
      through local field inhomogeneities in and around deoxygenated red blood cells.
      In addition, this work shows that it is critical to choose the scan parameters
      carefully for robust oxygen-sensitive contrast. Finally, it is demonstrated that
      it is possible to build a quantitative model that incorporates the Luz-Meiboom
      model, which had been used in the past to estimate quantitative measures of
      vascular blood oxygen levels. It is envisioned that this method could be
      instrumental in real-time imaging focused on detecting diseases where the oxygen
      state of blood is impaired.

PMID- 15723411
TI  - Rapid fat-suppressed isotropic steady-state free precession imaging using true 3D
      multiple-half-echo projection reconstruction.
AB  - Three-dimensional projection reconstruction (3D PR)-based techniques are
      advantageous for steady-state free precession (SSFP) imaging for several reasons,
      including the capability to achieve short repetition times (TRs). In this paper,
      a multi-half-echo technique is presented that dramatically improves the data
      sampling efficiency of 3D PR sequences while it retains this short-TR capability.
      The k-space trajectory deviations are measured quickly and corrected on a per
      sample point basis. A two-pass RF cycling technique is then applied to the dual
      half-echo implementation to generate fat/water-separated images. The resultant
      improvement in the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)
      was demonstrated in volunteer studies. Volumetric images with excellent spatial
      resolution, coverage, and contrast were obtained with high speed. The non
      contrast-enhanced SSFP studies show that this technique has promising potential
      for MR angiography (MRA).

PMID- 15723412
TI  - Noise reduction in multi-slice arterial spin tagging imaging.
AB  - Attenuating the static signal in arterial spin tagging (ASSIST) was initially
      developed for 3D imaging of cerebral blood flow. To enable the simultaneous
      collection of cerebral blood flow and BOLD data, a multi-slice version of ASSIST
      is proposed. As with the 3D version, this sequence uses multiple inversion pulses
      during the tagging period to suppress the static signal. To maintain background
      suppression in all slices, the multi-slice sequence applies additional inversion
      pulses between slice acquisitions. The utility of the sequence was demonstrated
      by simultaneously acquiring ASSIST and BOLD data during a functional task and by
      collecting resting-state ASSIST data over a large number of slices. In addition,
      the temporal stability of the perfusion signal was found to be 60% greater at 3 T
      compared to 1.5 T, which was attributed to the insensitivity of ASSIST to
      physiologic noise.

PMID- 15723413
TI  - Noninvasive in vivo MRI detection of neuritic plaques associated with iron in
      APP[V717I] transgenic mice, a model for Alzheimer's disease.
AB  - Transgenic mice overexpressing the London mutant of human amyloid precursor
      protein (APP[V717I]) in neurons develop amyloid plaques in the brain, thus
      demonstrating the most prominent neuropathological hallmark of Alzheimer's
      disease. In vivo 3D T2*-weighted MRI on these mice (24 months of age) revealed
      hypointense brain inclusions that affected the thalamus almost exclusively. Upon
      correlating these MRI observations with a panel of different histologic staining
      techniques, it appeared that only plaques that were positive for both thioflavin
      S and iron were visible on the MR images. Numerous thioflavin-S-positive plaques
      in the cortex that did not display iron staining remained invisible to MRI. The
      in vivo detection of amyloid plaques in this mouse model, using the intrinsic MRI
      contrast arising from the iron associated with the plaques, creates an unexpected
      opportunity for the noninvasive investigation of the longitudinal development of
      the plaques in the same animal. Thus, this work provides further research
      opportunities for analyzing younger APP[V717I] mouse models with the knowledge of
      the final outcome at 24 months of age.

PMID- 15723414
TI  - Partially parallel imaging with phase-sensitive data: Increased temporal
      resolution for magnetic resonance temperature imaging.
AB  - Magnetic resonance temperature imaging can be used to monitor the progress of
      thermal ablation therapies, increasing treatment efficacy and improving patient
      safety. High temporal resolution is important when therapies rapidly heat tissue,
      but many approaches to faster image acquisition compromise image resolution,
      slice coverage, or phase sensitivity. Partially parallel imaging techniques offer
      the potential for improved temporal resolution without forcing such concessions.
      Although these techniques perturb image phase, relative phase changes between
      dynamically acquired phase-sensitive images, such as those acquired for MR
      temperature imaging, can be reliably measured through partially parallel imaging
      techniques using reconstruction filters that remain constant across the series.
      Partially parallel and non-accelerated phase-difference-sensitive data can be
      obtained through arrays of surface coils using this method. Average phase
      differences measured through partially parallel and fully Fourier encoded images
      are virtually identical, while phase noise increases with g(sqrt)L as in standard
      partially parallel image acquisitions..

PMID- 15723415
TI  - Characterization of intervertebral disc degeneration by high-resolution magic
      angle spinning (HR-MAS) spectroscopy.
AB  - The goal of this study was to determine the ability of high-resolution magic
      angle spinning (HR-MAS) NMR spectroscopy to distinguish different stages of
      intervertebral disc degeneration (IVDD). 17 discs were removed from human
      cadavers and analyzed them using 1D and 2D (total correlation spectroscopy
      (TOCSY)) (1)H HR-MAS spectroscopy, and T(1) and T(2) relaxation time measurements
      to determine the chemical composition and changes in chemical environment of
      discs with increasing levels of degeneration (Thompson grade). Among the
      significant findings were that spectra were very similar for samples taken from
      annular and nuclear regions of discs, and that visually apparent changes were
      observed in the spectra of the annular and nuclear samples from discs with
      increasing Thompson grade. Area ratios of the N-acetyl to choline (Cho) regions,
      and Cho to carbohydrate (Carb) regions of the spectra allowed us to discriminate
      between discs of increasing Thompson grade with minimal overlap of individual
      ratios. Changes in T(1) and T(2) relaxation times of the chemical constituents of
      disc spectra were not significantly correlated to the degree of degeneration. The
      results of this study support the feasibility of using in vivo spectroscopy for
      detecting chemical changes associated with disc degeneration.

PMID- 15723416
TI  - In vivo assessment of absolute perfusion and intracapillary blood volume in the
      murine myocardium by spin labeling magnetic resonance imaging.
AB  - The absolute perfusion and the intracapillary or regional blood volume (RBV) in
      murine myocardium were assessed in vivo by spin labeling magnetic resonance
      imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution
      of 469 x 469 mum and a slice thickness of 2 mm. The T(1) imaging module was a
      segmented inversion recovery snapshot fast low angle shot sequence with velocity
      compensation in all three gradient directions. The group average myocardial
      perfusion at baseline was determined to be 701 +/- 53 mL (100 g . min)(-1) for
      anesthesia with isoflurane (N = 11) at a mean heart rate (HR) of 455 +/- 10 beats
      per minute (bpm). This value is in good agreement with perfusion values
      determined by invasive microspheres examinations. For i.v. administration of the
      anesthetic Propofol, the baseline perfusion decreased to 383 +/- 40 mL (100 g .
      min)(-1) (N = 17, P < 0.05 versus. isoflurane) at a mean heart rate of 261 +/- 13
      bpm (P < 0.05 versus isoflurane). In addition, six mice with myocardial
      infarction were studied under isoflurane anesthesia (HR 397 +/- 7 bpm). The
      perfusion maps showed a clear decrease of the perfusion in the infarcted area.
      The perfusion in the remote myocardium decreased significantly to 476 +/- 81 mL
      (100 g . min)(-1) (P < 0.05 versus sham). Regarding the regional blood volume, a
      mean value of 11.8 +/- 0.8 vol % was determined for healthy murine myocardium
      under anesthesia with Propofol (N = 4, HR 233 +/- 17 bpm). In total, the
      presented techniques provide noninvasive in vivo assessment of the perfusion and
      the regional blood volume in the murine myocardium for the first time and seem to
      be promising tools for the characterization of mouse models in cardiovascular
      research.

PMID- 15723417
TI  - Spatially and temporally specific expression in mouse hippocampus of Usp9x, a
      ubiquitin-specific protease involved in synaptic development.
AB  - We studied the distribution of the ubiquitin-specific protease Usp9x in mouse
      brain as it relates to the potential role of ubiquitin proteasome system in
      synaptic plasticity. Usp9x is the mouse homolog of faf, known for its function in
      synaptic development in Drosophila. In adults, high levels of expression of Usp9x
      protein were found in layer V of neocortex, Purkinje cells in cerebellum, and
      specific hippocampal subfields. In hippocampal pyramidal cells, Usp9x expression
      was higher in CA3 than in CA1. This regional specificity was detected at
      postnatal day 22 but not at postnatal day 15. In adult mice, the CA1-CA3
      difference was partially accounted for by a difference in the level of Usp9x
      mRNA, suggesting that transcription of Usp9x was differentially regulated between
      hippocampal subfields. Two synaptic marker proteins, synaptotagmin and
      spinophilin, were both more abundant in the striatum oriens of CA3 than in the
      similar region of CA1, correlating with the distribution of Usp9x, a result
      compatible with a role for Usp9x in synaptic development in mouse hippocampus.
      Ube1x, the enzyme responsible for the initial step in ubiquitin conjugation, was
      preferentially concentrated in the dendrites of the CA1 neurons instead of the
      CA3 neurons, suggesting a reciprocal relationship between ubiquitin conjugation
      and deubiquitination in CA3 and CA1. This spatial and temporal specificity in
      expression of Usp9x and Ube1x protein raises interesting questions about the
      roles of these ubiquitin enzymes in the differential functions of CA1 and CA3.

PMID- 15723418
TI  - Selective homonuclear Hartmann-Hahn transfer method for in vivo spectral editing
      in the human brain.
AB  - A novel selective homonuclear Hartmann-Hahn transfer method for in vivo spectral
      editing is proposed and applied to measurements of gamma-aminobutyric acid (GABA)
      in the human brain at 3 T. The proposed method utilizes a new concept for in vivo
      spectral editing, the spectral selectivity of which is not based on a
      conventional editing pulse but based on the stringent requirement of the doubly
      selective Hartmann-Hahn match. The sensitivity and spectral selectivity of GABA
      detection achieved by this doubly selective Hartmann-Hahn match scheme was
      superior to that achievable by conventional in vivo spectral editing techniques
      providing both sensitivity enhancement and excellent suppression of overlapping
      resonances in a single shot. Since double-quantum filtering gradients were not
      employed, singlets such as the NAA methyl group at 2.02 ppm and the creatine
      methylene group at 3.92 ppm were detected simultaneously. These singlets may
      serve as navigators for the spectral phase of GABA and for frequency shifts
      during measurements. The estimated concentration of GABA in the frontoparietal
      region of the human brain in vivo was 0.7 +/- 0.2 mumol/g (mean +/- SD, n = 12).

PMID- 15723419
TI  - Diagnostic issues for adolescents and adults with ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common childhood
      neuropsychiatric syndrome once thought to disappear with maturation. Current data
      indicate that ADHD remains "hidden" in many of the grown-ups who had it as
      children. Adult prevalence rates range from 1% to 6% of the population. Research
      suggests the core childhood symptoms of hyperactivity, inattention, and
      impulsivity shift with development, perhaps transforming into more overt
      difficulties in executive functions and affect regulation. ADHD is also usually
      nestled with other comorbid psychiatric conditions, especially in adolescents and
      adults, further complicating diagnosis and treatment. This article discusses how
      to recognize and diagnose ADHD in older patients. Key points include core
      symptoms present during childhood, appropriate family history in this strongly
      genetic condition, management of comorbidity, and the evolving role of diagnostic
      testing. Other medical causes for similar symptoms are considered.

PMID- 15723421
TI  - SU-16: a three-dimensional open-framework borogermanate with a novel zeolite
      topology.

PMID- 15723420
TI  - Attention deficit hyperactivity disorder in teens and adults: they don't all
      outgrow it.
AB  - Attention deficit hyperactivity disorder (ADHD) has been long recognized and well
      established in children, but its continuation into adulthood has only recently
      been supported by the research. ADHD symptoms and concerns typically appear
      differently in adults, but treatment options, conceptually at least, are similar
      to those used for children who have ADHD. This article introduces the issue of
      Journal of Clinical Psychology: In Session devoted to ADHD in teens and adults.
      It presents the prevalence and manifestations of the disorder and then reviews
      the subsequent articles on the comorbidity, evaluation, education,
      psychopharmacology, and psychosocial treatments of ADHD for teens and adults. The
      issue concludes with an article on neurobiofeedback, a relatively new treatment
      option.

PMID- 15723422
TI  - Three-spin system with a twist: a bis(semiquinonato)copper complex with a
      nonplanar configuration at the copper(II) center.

PMID- 15723423
TI  - ADHD couple and family relationships: enhancing communication and understanding
      through Imago Relationship Therapy.
AB  - This article reviews the relationship deficits experienced by many individuals
      who have attention deficit hyperactivity disorder (ADHD) and proposes effective
      strategies, based on Imago Relationship Therapy (IRT), to assist them in
      communicating more effectively. The neurological underpinnings of the disorder
      often contribute to the development of poor social and communication skills and
      can lead to a lifetime of relationship difficulties. IRT, a brain-based approach,
      is compatible with the neurological challenges of living with ADHD because it
      slows the communication process, provides structure, reduces reactivity, and
      helps individuals to be fully present so that their loved one can feel fully
      heard and understood. The couple's dialogue strengthens relationships by
      encouraging the development of stronger listening skills, better self-control,
      and problem solving. Two case examples illustrate the clinical methods used.

PMID- 15723424
TI  - Career choices and workplace challenges for individuals with ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) in adults is increasingly
      recognized as a common disorder that can significantly impact workplace
      functioning, yet few clinicians or career consultants have training in how to
      help adults select careers or jobs within a chosen career that are a good match
      for their strengths, weaknesses, ADHD tendencies, and coexisting conditions.
      Straightforward career counseling is inadequate to meet the needs of adults who
      have ADHD, and significant follow-up, brain-based counseling or therapy is often
      necessary to help these adults implement the recommendations generated by an ADHD
      career assessment. This article guides the clinician through the multiple steps
      of clinical interview, assessment, and intervention when working with adults who
      have ADHD who face challenges in the workplace.

PMID- 15723425
TI  - Treating adolescent girls and women with ADHD: gender-specific issues.
AB  - Attention deficit hyperactivity disorder (ADHD), commonly diagnosed in males, is
      often a "hidden disorder" in girls and women. This lack of recognition can be
      partially explained because the symptoms are less overt in females. In addition,
      coexisting disorders in females are often different from those seen in males who
      have ADHD. Higher rates of anxiety, mood, and substance disorders, as well as
      learning disabilities, often complicate the picture. Thus, clinicians are
      challenged with disentangling the symptoms of ADHD from symptoms of these
      coexisting conditions. In addition, fluctuating hormone levels may affect ADHD
      symptoms and treatment in females. Only with gender-sensitive diagnosis and
      treatment will the public health concern posed by the underdiagnosis of ADHD in
      females be addressed. This case report of a 23-year-old female illustrates the
      specific difficulties with the gender-sensitive aspects of the diagnosis and
      treatment of ADHD in females.

PMID- 15723426
TI  - Adjusting for observable selection bias in block randomized trials.
AB  - In this paper, we propose a model-based approach to detect and adjust for
      observable selection bias in a randomized clinical trial with two treatments and
      binary outcomes. The proposed method was evaluated using simulations of a
      randomized block design in which the investigator favoured the experimental
      treatment by attempting to enroll stronger patients (with greater probability of
      treatment success) if the probability of the next treatment being experimental
      was high, and enroll weak patients (with less probability of treatment success)
      if the probability of the next treatment being experimental was low. The method
      allows not only testing for the presence of observable selection bias, but also
      testing for a difference in treatment effects, adjusting for possible selection
      bias.

PMID- 15723427
TI  - Interspecies pharmacokinetic scaling of oltipraz in mice, rats, rabbits and dogs,
      and prediction of human pharmacokinetics.
AB  - Dose-independent pharmacokinetics of oltipraz after intravenous and/or oral
      administration at various doses to mice, rats, rabbits and dogs were evaluated.
      After both intravenous and/or oral administration of oltipraz to mice (5, 10 and
      20 mg/kg for intravenous and 15, 30 and 50 mg/kg for oral administration), rats
      (5, 10 and 20 mg/kg for intravenous and 25, 50 and 100 mg/kg for oral
      administration), rabbits (5, 10 and 30 mg/kg for intravenous administration) and
      dogs (5 and 10 mg/kg for intravenous and 50 and 100 mg/kg for oral
      administration), the total area under the plasma concentration-time curve from
      time zero to time infinity (AUC) values of oltipraz were dose-proportional in all
      animals studied. Animal scale-up of some pharmacokinetics parameters of oltipraz
      was also performed based on the parameters after intravenous administration at a
      dose of 10 mg/kg to mice, rats, rabbits and dogs. Linear relationships were
      obtained between log time-averaged total body clearance (Cl) x maximum life-span
      potential (MLP) (1 year/h) and log species body weight (W) (kg) (r=0.999;
      p=0.0015), log Cl (l/h) and log W (kg) (r=0.979; p=0.0209), and log apparent
      volume of distribution at steady state (V(ss)) (l) and log W (kg) (r=0.999;
      p=0.0009). The corresponding allometric equations were ClxMLP=49.8 W(0.861),
      Cl=5.20 W(0.523) and V(ss)=4.46 W(0.764). Interspecies scale-up of plasma
      concentration-time data for the four species using pharmacokinetic time of
      dienetichron resulted in similar profiles. In addition, concentrations of
      oltipraz in a plasma concentration-time profile for humans predicted using the
      four animal data fitted to the dienetichron time transformation of animal data.

PMID- 15723428
TI  - Bioequivalence of two oral formulations of nizatidine capsules in healthy male
      volunteers.
AB  - PURPOSE: The purpose of this randomized, crossover study was to compare the
      bioavailability of a generic and an innovator formulation of nizatidine 300 mg
      capsules under fasting conditions. METHODS: Twenty blood samples per period were
      collected from 20 healthy, Arab male volunteers over 16 h, plasma nizatidine
      concentrations were determined by HPLC assay, and pharmacokinetic parameters were
      determined by the non-compartmental method. RESULTS: Mean+/-SD C(max), T(max),
      AUC(0-->t), AUC(0-->infinity), and t1/2 were 2.96+/-0.54 and 3.28+/-0.68
      microg/ml, 1.31+/-0.70 and 0.93+/-0.38 h, 9.04+/-1.66 and 9.03+/-1.94 microg x
      h/ml, 9.17+/-1.64 and 9.12+/-1.94 microg x h/ml, and 1.64+/-0.21 and 1.58+/-0.22
      h for the generic and innovator formulation, respectively. The parametric 90%
      confidence intervals on the mean of the difference between log-transformed values
      were 98.06% to 103.21%, 98.74% to 103.71%, and 83.37% to 101.34%, for AUC(0-->t),
      AUC(0-->infinity), and C(max), respectively. CONCLUSION: The results indicate
      that these two formulations are equivalent in the rate and extent of absorption.

PMID- 15723429
TI  - Intramolecular hydrogen bonds and charge-remote fragmentations in negative-ion
      mass spectrometry of dihydroxylated fatty acids.

PMID- 15723432
TI  - A functional model of the cytochrome c oxidase active site: unique conversion of
      a heme-mu-peroxo-Cu(II) intermediate into heme- superoxo/Cu(I).

PMID- 15723431
TI  - Total synthesis of caprazol, a core structure of the caprazamycin
      antituberculosis antibiotics.

PMID- 15723433
TI  - Oxazoline-mediated interannular cyclopalladation of ferrocene: chiral
      palladium(II) catalysts for the enantioselective Aza-Claisen rearrangement.

PMID- 15723434
TI  - One-dimensional assembly of lipophilic inorganic nanoparticles templated by
      peptide-based nanofibers with binding functionalities.

PMID- 15723435
TI  - Liquid chromatography/mass spectrometry analysis of bifunctional electrophiles
      and DNA adducts from vitamin C mediated decomposition of 15
      hydroperoxyeicosatetraenoic acid.
AB  - Reactive oxygen species convert the omega-6 polyunsaturated fatty acid
      arachidonic acid into 15-hydroperoxy-5,8,11,13-(Z,Z,ZE)-eicosatetraenoic acid (15
      HPETE). Cyclooxygenases and lipoxygenases can also convert arachidonic acid into
      15-HPETE. Vitamin C mediated decomposition of 15(S)-HPETE to protein- and DNA
      reactive bifunctional electrophiles was examined by normal-phase liquid
      chromatography/atmospheric pressure chemical ionization/mass spectrometry
      (LC/APCI-MS). The individual bifunctional electrophiles, trans-4,5-epoxy-2(E)
      decenal (t-EDE), cis-4,5-epoxy-2(E)-decenal (c-EDE), 4-oxo-2(E)-nonenal (ONE),
      and 4-hydroxy-2(E)-nonenal (HNE), exhibited protonated molecules at m/z 169, 169,
      155, and 157, respectively. The MH+ ion at m/z 173 for 4-hydroperoxy-2(E)-nonenal
      (HPNE) was very weak with an ion corresponding to the loss of OH at m/z 156 as
      the major ion in the APCI mass spectrum. The bifunctional electrophiles were all
      separated under normal-phase LC conditions. All five bifunctional electrophiles
      were formed when 15-HPETE was treated with vitamin C. The LC/MS-based methodology
      showed that t-EDE was the major bifunctional electrophile formed during vitamin C
      mediated 15(S)-HPETE decomposition. Stable isotope dilution LC/MS studies
      revealed that this did not result in the formation of increased levels of
      unsubstituted etheno-dGuo adducts in calf thymus DNA when compared with 13(S)
      hydroperoxy-9,10-(Z,E)-octadecadienoic acid [13(S)-HPODE], a lipid hydroperoxide
      derived from linoleic acid. However, the formation of heptanone-etheno-dGuo
      adducts in calf thymus DNA was reduced when compared with the 13(S)-HPODE. This
      was attributed to the reduced formation of ONE from 15-HPETE when compared with
      its formation from 13-HPODE. In contrast to reactions with dGuo or DNA conducted
      using 13(S)-HPODE, no carboxy-containing adducts were observed with 15(S)-HPETE.

PMID- 15723436
TI  - Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly
      diagnosed chronic liver disease.
AB  - We performed a cross-sectional study of newly diagnosed cases of nonalcoholic
      fatty liver disease (NAFLD) identified between December 1998 and December 2000 in
      the Chronic Liver Disease Surveillance Study. We compared the demographic and
      clinical features of NAFLD in a racially diverse representative U.S. population
      (Alameda County, CA). Diagnostic criteria for probable NAFLD were persistent
      unexplained elevation of serum aminotransferase levels, radiology (ultrasound or
      computed tomography scan) consistent with fatty liver, and/or two or more of the
      following: (i) body mass index of 28 kg/m(2) or more, (ii) type 2 diabetes, or
      (iii) hyperlipidemia, in the absence of significant alcohol use. Definite NAFLD
      cases required histological confirmation. Of the 742 persons with newly diagnosed
      chronic liver disease, 159 (21.4%) had definite or probable NAFLD. The majority
      were nonwhite: Hispanics (28%), Asians (18%), African Americans (3%), and other
      race(s) (6%). African Americans with NAFLD were significantly older than other
      racial or ethnic groups (P < .001), and in Asians, NAFLD was 3.5 times more
      common in males than in females (P = .016). Clinical correlates of NAFLD
      (obesity, hyperlipidemia, diabetes) were similar among racial and ethnic groups,
      except that body mass index was lower in Asians compared with other groups (P <
      .001). Compared with the base population (Kaiser Permanente members), Hispanics
      with NAFLD were overrepresented (28% vs. 10%) and whites were underrepresented
      (45% vs. 59%). In conclusion, these racial and gender variations may reflect
      differences in genetic susceptibility to visceral adiposity, including hepatic
      involvement, and may have implications for the evaluation of persons with the
      metabolic syndrome. Clinicians need to be aware of the variable presentations of
      NAFLD in different racial and ethnic groups.

PMID- 15723437
TI  - Cytokine-independent repression of rodent Ntcp in obstructive cholestasis.
AB  - Cholestatic liver injury is associated not only with accumulation of bile acids
      but also with activation of proinflammatory cytokines. Common bile duct ligation
      (CBDL) induces sustained downregulation of the Na(+)/taurocholate cotransporter
      (Ntcp) in rodent liver. Although repression of Ntcp during endotoxemia is
      cytokine mediated, it is unclear whether inflammatory cytokines contribute to
      this downregulation in obstructive cholestasis. Cytokine inactivation in CBDL
      rats and mice was either performed directly with tumor necrosis factor alpha
      (etanercept) or interleukin 1 beta inactivation (anakinra/AMG 719) or indirectly
      Kupffer cell depletion via intraperitoneal administration of liposome
      encapsulated dichloromethylene bisphosphonate. Protein and messenger RNA (mRNA)
      expression of Ntcp and short heterodimer partner (SHP) were analyzed via Western
      and Northern blotting. Key regulators of Ntcp (hepatocyte nuclear factor 1 alpha
      [HNF-1alpha], HNF-4alpha, retinoid X receptor alpha [RXRalpha]:retinoic acid
      receptor alpha [RARalpha]) were studied via electrophoretic mobility shift
      analysis and nuclear Western blot analysis. Both methods of cytokine inactivation
      failed to maintain Ntcp protein or mRNA expression within 3 days after CBDL in
      either rats or mice (20%-40% of sham controls), while SHP mRNA expression
      increased three- to five-fold. Decreased nuclear HNF-1alpha and HNF-4alpha
      protein levels (45% and 60% of sham controls, respectively) and HNF-1alpha
      binding activity (32% of sham controls) were not restored during cytokine
      inactivation after CBDL, indicating cytokine-independent mechanisms of Ntcp
      regulation. RXRalpha:RARalpha binding remained unchanged in all experimental
      conditions. In conclusion, during obstructive cholestasis accumulating bile acids
      per se, without major contribution of cytokines, leads to downregulation of Ntcp
      via repression of HNF-1alpha and HNF-4alpha.

PMID- 15723438
TI  - TNFalpha-mediated extracellular matrix remodeling is required for multiple
      division cycles in rat hepatocytes.
AB  - During liver regeneration, hepatocytes proliferate under the control of both
      proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and
      growth factors, in parallel to extracellular matrix remodeling. This study
      investigated mechanisms by which mitogen and extracellular matrix signals are
      linked for inducing proliferation of differentiated hepatocytes. The authors used
      adult rat hepatocytes in coculture with liver biliary cells, because cells are
      stably differentiated for several weeks, capable of extracellular matrix
      deposition, and unable to divide in response to growth factor alone. This work
      demonstrated that hepatocytes could undergo several proliferation waves without
      loss of differentiation by using alternating periods of TNFalpha/growth factor
      stimulation and deprivation. Three days after stimulation with TNFalpha and
      epidermal growth factor (EGF), up to 35% of hepatocytes divided. Demonstration
      was also provided that EGF alone only promoted cell progression up to late G(1),
      whereas TNFalpha was necessary for G(1)/S transition and Cdk1 induction. TNFalpha
      promoted an extracellular matrix (ECM) degradation that involved the matrix
      metalloproteinase MMP-9 induction through activation of NF-kappaB pathway.
      Finally, the authors showed that ECM remodeling signal was required for
      initiating any new hepatocyte division wave, in presence of mitogen. In
      conclusion, these results highlight that hepatocyte division is dependent on ECM
      deposition associated with differentiation status, and that ECM degradation
      signal is critical in controlling G(1)/S transition and Cdk1 induction. These
      results provide new insights for understanding the unique hepatocyte
      proliferation control and improving regeneration in patients suffering from liver
      damage.

PMID- 15723439
TI  - Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice.
AB  - The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease
      gene indicated that Notch signaling has an important role in bile duct
      homeostasis. The functional study of this signaling pathway has been difficult
      because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an
      embryonic lethal phenotype. We have previously generated mice with inducible
      Notch1 disruption using an interferon-inducible Cre-recombinase transgene in
      combination with the loxP flanked Notch1 gene. We used this conditional Notch1
      knockout mouse model to investigate the role of Notch1 signaling in liver cell
      proliferation and differentiation. Deletion of Notch1 did not result in bile duct
      paucity, but, surprisingly, resulted in a continuous proliferation of
      hepatocytes. In conclusion, within weeks after Notch1 inactivation, the mice
      developed nodular regenerative hyperplasia without vascular changes in the liver.

PMID- 15723440
TI  - Toward semisynthetic lipoproteins by convergent strategies based on click and
      ligation chemistry.

PMID- 15723441
TI  - Design, synthesis and antimalarial activity of trifluoromethylartemisinin
      mefloquine dual molecules.

PMID- 15723442
TI  - A method for quantitative determination of deuterium content in biological
      material.
AB  - A method was developed for quantitative determination of deuterium incorporated
      into live organisms or biological macromolecules. The deuterated biological
      material was mixed with a bovine serum albumin (BSA) supporter to make a
      homogeneous sample for which the deltaD value (vs. VSMOW) was analyzed using a
      dual-inlet gas isotope mass spectrometer. The method is described in detail, and
      the equation for calculation of deuterium content is presented, i.e., CbioD=1/500
      x k x RVSMOW x CBSAH x 10(6) ppm. Deuterated hepatitis A virus (HAV) RNA and BSA
      were systematically investigated. The results demonstrate that the method is
      capable of direct measurement of deuterium content, and is highly repeatable and
      reliable with a standard deviation of +/-3 per thousand. It is stressed that the
      quantity of deuterated sample required is extremely small as a result of using
      BSA as supporter. The method may be applied in many fields, and has the strengths
      of simplicity, relative cheapness, and robustness.

PMID- 15723443
TI  - Hardware-accelerated protein identification for mass spectrometry.
AB  - An ongoing issue in mass spectrometry is the time it takes to search DNA
      sequences with MS/MS peptide fragments (see, e.g., Choudary et al., Proteomics
      2001; 1: 651-667.) Search times are far longer than spectra acquisition time, and
      parallelization of search software on clusters requires doubling the size of a
      conventional computing cluster to cut the search time in half. Field programmable
      gate arrays (FPGAs) are used to create hardware-accelerated algorithms that
      reduce operating costs and improve search speed compared to large clusters. We
      present a novel hardware design that takes full spectra and computes 6-frame
      translation word searches on DNA databases at a rate of approximately 3 billion
      base pairs per second, with queries of up to 10 amino acids in length and
      arbitrary wildcard positions. Hardware post-processing identifies in silico
      tryptic peptides and scores them using a variety of techniques including mass
      frequency expected values. With faster FPGAs protein identifications from the
      human genome can be achieved in less than a second, and this makes it an ideal
      solution for a number of proteome-scale applications.

PMID- 15723444
TI  - Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse
      model of hepatocarcinogenesis.
AB  - We developed hepatitis C virus (HCV) core-E1-E2 and HCV core transgenic mice on a
      common genetic background to assess the contribution of HCV structural proteins
      to hepatocarcinogenesis. Eight-week-old core-E1-E2, core, and nontransgenic mice
      inbred on the FVBxC57Bl/6 background were treated with diethylnitrosamine (DEN)
      and sacrificed at 32 weeks old. Proliferation and apoptosis were assessed by
      immunohistochemistry. The effect of viral proteins on apoptosis was evaluated in
      HepG2 cells in which apoptosis was induced by anti-Fas antibody. HCCs were
      identified at 32 weeks in the majority of DEN-treated mice from all three groups.
      The mean size of HCCs was significantly larger in core-E1-E2 transgenic (4.63 +/-
      1.48 mm), compared with core transgenic (0.78 +/- 0.26 mm, P = .01), and
      nontransgenic (1.0 +/- 0.19 mm, P = .002) mice. While there were no differences
      in proliferation, the apoptotic index in core-E1-E2 transgenic HCCs was
      significantly lower than those found in core and non-transgenic HCCs. Core-E1-E2
      transfected HepG2 cells demonstrated a significantly lower apoptotic index (0.35
      +/- 0.11) compared with that of core transfected cells (0.74 +/- 0.07, P =
      .0103). Analysis of a Fas-induced apoptosis model in HCV transgenic mice
      confirmed that core-E1-E2 transgenic liver underwent significantly less apoptosis
      than transgenic tissue expressing core only. In conclusion, HCV core-E1-E2
      transgenic mice develop significantly larger tumors than transgenic mice
      expressing core alone or nontransgenic mice. The accelerated tumor phenotype is
      attributable to suppression of apoptosis rather than enhanced proliferation.
      These data implicate HCV E1 and/or E2 in conjunction with core as antiapoptotic,
      tumor accelerator proteins.

PMID- 15723445
TI  - Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth
      factor in rat liver regeneration.
AB  - Prostaglandins are hepatoprotective molecules generated in liver regeneration by
      the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and
      vascular endothelial growth factor (VEGF) are other hepatoprotective mediators
      upregulated at 24 hours after partial hepatectomy. The interactions among these
      molecules during liver regeneration have not yet been defined. Here we show that
      rats subjected to partial hepatectomy treated with NS-398, a specific COX-2
      inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis,
      persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and
      increased interleukin-6 production. These changes were associated with
      downregulation of CT-1 and COX-1 and altered pattern of VEGF expression.
      Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted
      normal levels of COX-1, prostaglandins, and VEGF in the liver after partial
      hepatectomy and restored normal liver regeneration. Furthermore, the stimulation
      of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger
      RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to
      the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation
      and production of prostaglandins soon after partial hepatectomy are essential
      requirements for hepatocyte proliferation and for the correct induction of both
      CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by
      increasing VEGF, COX-1 expression, and prostaglandin synthesis.

PMID- 15723446
TI  - Increasing throughput and information content for in vitro drug metabolism
      experiments using ultra-performance liquid chromatography coupled to a quadrupole
      time-of-flight mass spectrometer.
AB  - The field of drug metabolism has been revolutionized by liquid
      chromatography/mass spectrometry (LC/MS) applications with new technologies such
      as triple quadrupoles, ion traps and time-of-flight (ToF) instrumentation. Over
      the years, these developments have often relied on the improvements to the mass
      spectrometer hardware and software, which has allowed users to benefit from lower
      levels of detection and ease-of-use. One area in which the development pace has
      been slower is in high-performance liquid chromatography (HPLC). In the case of
      metabolite identification, where there are many challenges due to the complex
      nature of the biological matrices and the diversity of the metabolites produced,
      there is a need to obtain the most accurate data possible. Reactive or toxic
      metabolites need to be detected and identified as early as possible in the drug
      discovery process, in order to reduce the very costly attrition of compounds in
      late-phase development. High-resolution, exact mass measurement plays a very
      important role in metabolite identification because it allows the elimination of
      false positives and the determination of non-trivial metabolites in a much faster
      throughput environment than any other standard current methodology available to
      this field. By improving the chromatographic resolution, increased peak capacity
      can be achieved with a reduction in the number of co-eluting species leading to
      superior separations. The overall enhancement in the chromatographic resolution
      and peak capacity is transferred into a net reduction in ion suppression leading
      to an improvement in the MS sensitivity. To investigate this, a number of in
      vitro samples were analyzed using an ultra-performance liquid chromatography
      (UPLC) system, with columns packed with porous 1.7 mum particles, coupled to a
      hybrid quadrupole time-of-flight (ToF) mass spectrometer. This technique showed
      very clear examples for fundamental gains in sensitivity, chromatographic
      resolution and speed of analysis, which are all important factors for the demands
      of today's HTS in discovery.

PMID- 15723447
TI  - Hyperhydroxyprolinaemia: a new case diagnosed during neonatal screening with
      tandem mass spectrometry.

PMID- 15723448
TI  - Effects of celecoxib and naproxen on renal function in nonazotemic patients with
      cirrhosis and ascites.
AB  - Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory
      drugs frequently induces renal failure in decompensated cirrhosis. Studies in
      experimental cirrhosis suggest that selective inhibitors of the inducible isoform
      COX-2 do not adversely affect renal function. However, very limited information
      is available on the effects of these compounds on renal function in human
      cirrhosis. This investigation consists of a double-blind, randomized, placebo
      controlled trial aimed at comparing the effects of the selective COX-2 inhibitor
      celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal
      function and the renal response to furosemide (40 mg intravenously) with those of
      naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28
      patients with cirrhosis and ascites. A significant reduction (P < .05) in
      glomerular filtration rate (113 +/- 27 to 84 +/- 22 mL/min), renal plasma flow
      (592 +/- 158 to 429 +/- 106 mL/min) and urinary prostaglandin E(2) excretion
      (3430 +/- 430 to 2068 +/- 549 pg/min) and suppression of the diuretic (urine
      volume: 561 +/- 128 to 414 +/- 107 mL/h) and natriuretic (urine sodium: 53 +/- 13
      to 34 +/- 10 mEq/h) responses to furosemide were observed in the group of
      patients treated with naproxen but not in the other two groups. Naproxen, but not
      celecoxib or placebo, significantly inhibited platelet aggregation (72% +/- 8% to
      47% +/- 8%, P < .05) and thromboxane B(2) production (41 +/- 12 to 14 +/- 5
      pg/mL, P < .05). In conclusion, our results indicate that short-term
      administration of celecoxib does not impair platelet and renal function and the
      response to diuretics in decompensated cirrhosis. Further studies are needed to
      evaluate the long-term safety of this drug in cirrhosis.

PMID- 15723449
TI  - Non-Hodgkin's lymphoma and other nonhepatic malignancies in Swedish patients with
      hepatitis C virus infection.
AB  - The aim of this study was to evaluate the association between hepatitis C virus
      (HCV) infection and non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), thyroid
      cancer (TC), chronic lymphatic leukemia (CLL), acute lymphatic leukemia (ALL),
      and Hodgkin's lymphoma (HL). A Swedish cohort of 27,150 HCV-infected persons
      notified during 1990-2000 was included in the study. The database was linked to
      other national registers to calculate the observation time, expressed as person
      years, and to identify all incident malignancies in the cohort. The patients were
      stratified according to assumed time of previous HCV infection. The relative risk
      of malignancy was expressed as a standardized incidence ratio (SIR)-the observed
      number compared to the expected number. During 1990-2000 there were 50 NHL, 15
      MM, 14 ALL, 8 TC, 6 CLL, and 4 HL diagnoses in the cohort. Altogether, 20 NHL, 7
      MM, 5 TC, 4 CLL, 1 ALL, and 1 HL patient fulfilled the criteria to be included in
      the statistical analysis. The observation time was 122,272 person-years. The risk
      of NHL and MM was significantly increased in the stratum with more than 15 years
      of infection (SIR 1.89 [95% CI, 1.10-3.03] and 2.54 [95% CI, 1.11-5.69],
      respectively). The association was not significant in TC or CLL. In conclusion,
      we report the incidence of several malignancies in a nationwide cohort of HCV
      infected persons. Although the delayed diagnosis of HCV probably has resulted in
      an underestimation of the risk, this study showed a significantly increased risk
      of NHL and MM.

PMID- 15723450
TI  - Immunological effects of chimeric anti-GD3 monoclonal antibody KM871 in patients
      with metastatic melanoma.
AB  - We conducted an open label dose-escalation phase I trial of chimeric anti-GD3 mAb
      KM871 in patients with metastatic melanoma. Patients were entered into one of
      five dose levels (1, 5, 10, 20, and 40 mg/m2) and received three infusions of
      KM871 at 2-wk intervals. A metastatic melanoma site was biopsied at day 7-10.
      Pharmacokinetics, immune function, and mechanism of action of KM871 were
      analysed. A total of 17 patients were entered into the trial; 15 were evaluable.
      KM871 had a serum half-life (T1/2-beta) based on ELISA of 10.39 +/- 1.12 d (mean
      +/- SD). Trough levels >1.0 microg/mL KM871 at 2 wk postinfusion were seen with
      the 10 mg/m2 and higher dose levels. There were no significant changes in white
      blood cell subsets or serum complement levels during KM871 treatment. KM871 was
      stable in vivo and maintained binding affinity and complement-dependent
      cytotoxicity (CDC) function up to 2 wk postinfusion. No significant trends in CDC
      or antibody-dependent cellular-cytotoxicity (ADCC) activity in patients were
      observed during treatment. Analysis of tumour biopsies demonstrated a significant
      increase in CD4+ T cell infiltrates compared to control patient tumours (P =
      0.010), and in patients with either stable disease (2 patients) or a clinical
      partial response (1 patient) at restaging, a significant increase in CD3 and CD4
      infiltrates in tumour over nonresponding patients was observed. The favourable
      immune properties of KM871, combined with this preliminary clinical data,
      indicate that KM871 has potential for the treatment of metastatic melanoma.

PMID- 15723451
TI  - Au nanoparticles and polyaniline coated resin beads for simultaneous catalytic
      oxidation of glucose and colorimetric detection of the product.
AB  - In this letter, we report the synthesis of Au nanoparticles (NPs) and polyaniline
      (PANI) on the same cation-exchange resin beads and demonstrate their use in
      catalyzing the oxidation of glucose to gluconic acid by Au NPs and simultaneously
      in detecting the formation of the acid by the color change of PANI. The synthesis
      was carried out by exchanging the cations of the resins with HAuCl4 and
      anilinuium chloride and then reducing the metal ions by NaBH4 to produce Au NPs
      followed by polymerization of aniline using H2O2. The green emeraldine salt form
      of PANI thus obtained was treated with NaOH to be converted to blue emeraldine
      base before use. The deposition of Au NPs was confirmed by a change in color of
      the bead, visible spectroscopy, X-ray diffraction, and scanning electron
      microscopic measurements. On the other hand, the presence of PANI was confirmed
      by Fourier transform infrared (FTIR) and ultraviolet-visible (UV-vis)
      spectroscopy. The formation of gluconic acid from glucose was confirmed by FTIR
      spectroscopy. We could detect the presence of glucose of a minimum 1.0 mM
      concentration in water, using the present method. Our experimental observations
      demonstrate the possibility of the incorporation of multifunctional components on
      the surfaces of resins for carrying out a chemical reaction as well as detection
      of the product.

PMID- 15723452
TI  - Revisiting the S-Au(111) interaction: static or dynamic?
AB  - The Au-S interaction is probably the most intensively studied interaction of Au
      surfaces with nonmetals, as, for example, it plays an important role in Au ore
      formation(1) and controls the structure and dynamics of thiol-based self
      assembled monolayers (SAMs). Various S-induced surface structures on Au(111) were
      recently reported for different conditions and predominantly interpreted in terms
      of a static Au surface. Here, we demonstrate that the Au(111) surface exhibits a
      very dynamic character upon interaction with adsorbed sulfur: large-scale surface
      restructuring and incorporation of Au atoms into a growing 2D AuS phase were
      observed in situ. These results provide new insight into the Au-S surface
      chemistry.

PMID- 15723453
TI  - Nanoscale patterning of flat carbon surfaces by scanning probe lithography and
      electrochemistry.
AB  - We report the formation of carbon surfaces patterned at the nanoscale with
      organic functionalities. Thin (<10 nm) films are covalently grafted to the
      surface via the electrochemical reduction of aryl diazonium salts. Areas of the
      film are removed with an AFM tip, and a second modifier is electrochemically
      grafted to the exposed surface. The pattern can incorporate different chemical
      functionalities, or alternatively topographical patterns can be assembled, where
      the same functionality is present throughout the pattern.

PMID- 15723454
TI  - Glued Langmuir-Blodgett bilayers having unusually high He/CO2 permeation
      selectivities.
AB  - Single Langmuir-Blodgett bilayers derived from 5,11,17,23,29,35-hexakis[(N,N,N
      trimethylammonium)-N-methyl-37,38,39,40,41,42-hexakis-n-hexamedecyloxy
      calix[6]arene hexachloride (1), which have been ionically cross-linked (i.e.,
      "glued together") with poly(acrylic acid), have been found to exhibit He/CO2
      permeation selectivities as high as 150. This degree of selectivity, for a
      membrane that is less than 6 nm in thickness, is without precedent. In principle,
      materials of this type could lead the way to improved membranes for hydrogen
      purification.

PMID- 15723455
TI  - Layer-by-layer assembly of human serum albumin and phospholipid nanotubes based
      on a template.
AB  - The preparation of nanotubes from human serum albumin (HSA) and mixtures of L
      alpha-dimyristoylphosphatidic acid (DMPA)/HSA is described. The nanotubes were
      prepared via alternate adsorption of HSA of different/opposite charges (by
      variation of the pH) or by sequential adsorption of DMPA and HSA, respectively,
      onto the inner surfaces of porous anodic alumina templates. This simple layer-by
      layer assembly results in a monodisperse size distribution and a uniform
      orientation. The nanotubes allow the specific incorporation of lipophilic
      components such as channels or receptors and may thus serve as probes or sensors
      for biological systems.

PMID- 15723456
TI  - Synthesis of bimetallic nanoshells by an improved electroless plating method.
AB  - In the Letter, we demonstrate an improved electroless plating method for the
      synthesis of bimetallic shell particles. The procedure involves a combination of
      surface reaction, seeding growth, and removal of supporting cores. We modified
      ammonical AgNO3 in ethanol with a controlled amount of HCHO in the seeding
      process and a uniform and relatively dense coverage of silver nanoparticle seeds
      on colloid cores was achieved. Following the second kind of metal plating, we
      extended this method to prepare continuous bimetallic core-shell and hollow
      particles with a submicrometer diameter. The morphologies of the bimetallic Cu/Ag
      and Pt/Ag particles were studied with transmission electron microscopy and
      scanning electron microscopy, and their crystallinity and chemical composition
      were confirmed by X-ray diffraction. The prepared materials may be of applied
      value in areas such as catalysis, optics, and plasmonics.

PMID- 15723457
TI  - Fluorescence quenching mechanism of a polyphenylene polyelectrolyte with other
      macromolecules: cytochrome c and dendrimers.
AB  - This study investigates the fluorescence quenching of a polyphenyl based
      polyelectrolyte by positively charged macromolecules (proteins and dendrimers).
      This work shows that the fluorescence quenching of the dendrimer materials does
      not involve energy transfer or electron transfer but is correlated to the overall
      charge on the dendrimer and its size. The quenching is hypothesized to result
      from conformational changes that occur upon binding the polyelectrolyte to the
      protein or dendrimer. This mechanism is qualitatively different from that invoked
      for small-molecule analytes.

PMID- 15723458
TI  - Fibrin proliferation at model surfaces: influence of surface properties.
AB  - Fibrin proliferation from both human fibrinogen solutions and platelet-poor
      plasma was studied quantitatively as a function of substrate surface properties.
      A quartz crystal microbalance was used to monitor both protein adsorption and
      fibrin proliferation in real time at hydrophobic, hydrophilic, positively
      charged, and negatively charged surfaces. Scanning electron microscopy was used
      to characterize the morphology of the polymerized fibrin layers. The observed
      changes in mass indicate that fibrinogen adsorption occurs rapidly and mediates
      subsequent fibrin proliferation. Notably, substrate surface properties
      significantly affect the ability of adsorbed fibrinogen to promote fibrin
      proliferation.

PMID- 15723459
TI  - Nanocrystal induced organization of a langmuir phospholipid monolayer.
AB  - The influence of crystal surface charge on the thermodynamic and structural
      behavior of phospholipid monolayers has been investigated. We present how charged
      nanocrystals in the vicinity of an inherently nonordered lipid membrane provoke
      strong effects on the molecular arrangement within the monolayer. Apart from the
      induction of phase shifts and nucleation processes, the molecules were forced to
      adopt an ordered phase. A very recently developed X-ray scattering method is used
      for the first time to replace time-consuming specular reflectivity measurements.
      We conclude on the potential effects of crystal surface charge on cellular
      membranes.

PMID- 15723460
TI  - Designing a capsule catalyst and its application for direct synthesis of middle
      isoparaffins.
AB  - A catalyst in the form of a capsule catalyst was prepared by coating HZSM5
      membrane on a preshaped Co/SiO2 catalyst pellet. The capsule catalyst with HZSM5
      membrane exhibited excellent selectivity for light hydrocarbon synthesis,
      especially for isoparaffin synthesis from syngas (CO + H2). Long-chain
      hydrocarbon formation was totally suppressed by the zeolite membrane. The
      modification of membrane and core catalyst significantly improved the catalytic
      properties of these new kinds of capsule catalysts.

PMID- 15723461
TI  - Nitrogen adsorption on silica xerogels or the odd look of a t plot.
AB  - Nitrogen adsorption in some silica xerogels leads to t plots that cannot be
      interpreted by the occurrence of capillary condensation or by the filling of
      micropores. Their particular appearance stems from the unique columnar structure
      of these samples at the nanometer scale, by which the adsorbent surface has a
      positive curvature. A standard thermodynamic approach allows the phenomenon to be
      exploited to characterize the samples.

PMID- 15723462
TI  - Nanotube foam prepared by gelatin gel as a template.
AB  - It has been known that simply mixing single-walled carbon nanotubes (SWCNTs) in
      an aqueous solution of gelatin disperses SWCNTs well for a period of months. Gels
      made from the gelatin-SWCNT mixture are also stable and have a clear, black
      color. Scanning electron microscopy shows that gelatin molecules self-organize
      into a foamlike structure. All SWCNTs are embedded in the gelatin film that makes
      up the foam walls. Those SWCNTs belonging to one face of the foam cell cannot
      approach other faces to make van der Waals contact. Thus, the foam structure is
      associated with stabilization of the SWCNT dispersion. The gelatin can be removed
      thermally while maintaining the foam structure to give a sponge made of nanotube
      foams. This highly porous solid is electrically conducting and mechanically
      stable and can be used as a structural frame for composite materials.

PMID- 15723463
TI  - Simple fabrication of micro lens arrays.
AB  - Microporous polymer films with a hexagonal arrangement of pores were prepared by
      simple casting of various polymer solutions under humid conditions. Hexagonally
      packed micropores were prepared by using condensed water droplets as templates on
      the surface of polymer solutions. Spherical micro lens arrays (MLAs) were
      fabricated simply by molding from the resulting honeycomb structures. By peeling
      off the upper layer with adhesive tape, the pillars were severed, forming pins on
      each layer, and a hexagonal array of pincushion structures was generated by this
      procedure. Hemispherical MLAs were also fabricated by molding the pincushion
      structures. The hemispherical MLAs projected clearer miniaturized images than
      spherical MLAs.

PMID- 15723464
TI  - Chemically tuned amphiphilic diblock copolymers dispersed in water: from colloids
      to soluble macromolecules.
AB  - We investigate by small-angle scattering the structural behavior in water of a
      family of asymmetric poly(styrene-stat-(acrylic acid))-block-poly(acrylic acid),
      i.e., P(S-stat-AA)-b-PAA, diblock copolymers. These diblocks are of constant
      block ratio and increasing molar fraction, phi(AA), ranging from 0 to 1, of
      acrylic acid in the first P(S-stat-AA) statistical block. We identify three types
      of structural behavior in water: (i) for phi(AA) </= 0.25, the structures found
      in water are out-of-equilibrium micelle-like objects, reminiscent of the
      macrophase separation in the solid state, with no reorganization upon dispersion;
      (ii) for phi(AA) >/= 0.50, the diblocks dispersions in water are at equilibrium.
      For high phi(AA), the diblocks are soluble in water, demonstrating that a
      transition from colloid-like objects to soluble macromolecules is achieved. Close
      to the transition, (phi(AA) approximately 0.50), the diblocks form objects
      interpreted as comprising a water-swollen core formed by the P(S-stat-AA) block,
      surrounded by a swollen brush composed of the majority PAA block, above a
      apparent critical micelle concentration. However, these diblocks do not behave as
      macrosurfactants, and their self-association behavior is rather interpreted as a
      microphase separation which can arise from the incompatibility between two
      polymer blocks P(S-stat-AA) and PAA placed in a common solvent water.

PMID- 15723465
TI  - Calculation of flocculation and coalescence rates for concentrated dispersions
      using emulsion stability simulations.
AB  - A simple procedure for the quantification of flocculation (k(f)) and coalescence
      (k(c)) rates from emulsion stability simulations (ESS) of concentrated systems is
      presented. It is based on a simple analytical equation, which results from the
      sum of well-known formulas for the separate processes of flocculation and
      coalescence. The expression contains k(f) and k(c) as fitting parameters and is
      found to reproduce the behavior predicted by ESS spanning a wide range of volume
      fractions (1 < phi < 30%) and surfactant concentrations (1.2 x10(-5) < C < 1.2 x
      10(-4) M). This procedure allows interpretation of ESS data in terms of the
      referred kinetic rates. Furthermore, it could also provide an additional mean for
      the direct comparison of the simulation data with experimental results.

PMID- 15723466
TI  - Sedimentation of a composite particle in a spherical cavity.
AB  - The boundary effect on the sedimentation of a colloidal particle is investigated
      theoretically by considering a composite sphere, which comprises a rigid core and
      an ion-penetrable membrane layer, in a spherical cavity. A pseudo-spectral method
      is adopted to solve the governing electrokinetic equations, and the influences of
      the key parameters on the sedimentation behavior of a particle are discussed. We
      show that both the qualitative and quantitative behaviors of a particle are
      influenced significantly by the presence of the membrane layer. For example, if
      the membrane layer is either free of fixed charge or positively charged and the
      surface potential of the rigid core is sufficiently high, the sedimentation
      velocity has a local minimum and the sedimentation potential has a local maximum
      as the thickness of the double layer varies. These local extrema are not observed
      when the membrane layer is negatively charged. If the double layer is thin, the
      influence of the fixed charge in the membrane layer on the sedimentation
      potential is inappreciable.

PMID- 15723467
TI  - Recycling nanoparticles stabilized in water-in-CO2 microemulsions for catalytic
      hydrogenations.
AB  - Catalytic hydrogenations of olefins took place effectively in supercritical CO2
      with Pd0 nanoparticles dispersed in the fluid phase using a water-in-CO2
      microemulsion consisting of water, sodium bis(2-ethylhexyl) sulfosuccinate (AOT)
      as a surfactant, and 1-octanol as a cosolvent. The hydrogenated products
      dissolved in supercritical CO2 can be separated from the octanol solution
      containing AOT microemulsions with Pd0 nanoparticles by phase separation (upper
      phase, supercritical CO2 with hydrogenated products; lower phase, 1-octanol
      containing AOT microemulsions with Pd0 nanoparticles) accompanied by reduction of
      CO2 pressure. After collecting the hydrogenated products by flowing the upper CO2
      phase to a collection vessel, the Pd0 nanoparticles remaining in the lower phase
      can be redispersed into supercritical CO2 by pressurizing the system to a
      pressure where a homogeneous phase is attained. The redispersed nanoparticles can
      be reused as catalysts for the next runs of the hydrogenations. Triphenylethylene
      was hydrogenated to 1,1,2-triphenylethane at conversions of 100% (1st-3rd runs),
      >99% (4th run), and >96% (5th run) using the recycled Pd0 nanoparticles. The
      feasibility of using other organic solvents as cosolvents is also studied in the
      present paper.

PMID- 15723468
TI  - Fluorescence probing of interior, interfacial, and exterior regions in solution
      aggregates of poly(ethylene oxide)- poly(propylene oxide)-poly(ethylene oxide)
      triblock copolymers.
AB  - Fluorescence spectroscopy is used to probe local environments within regions of
      different polarity and hydrophobicity in aqueous aggregates of PEO(109)-PPO(41)
      PEO(109) triblock copolymers. These copolymer aggregates have well characterized
      microphases in aqueous solution. Concentrations and temperatures for our studies
      are chosen such that the copolymers are in unimer, micellar, or micellar hydrogel
      forms. The observed fluorescence spectra and lifetimes from solutions
      individually labeled with each of the three coumarin probes report on the changes
      in the local polarity of the core, exterior, interfacial, and corona regions of
      these copolymer aggregates. This multiple fluorescence probe methodology will be
      straightforward to apply in general to problems in polymer and biopolymer
      aggregates, especially those that display strong hydrophobic effects.

PMID- 15723469
TI  - Wetting of regularly structured gold surfaces.
AB  - In this study we report results for a systematic study of the wetting of
      structured gold surfaces formed by electrodeposition through monolayer templates
      of close-packed uniform submicrometer spheres. Removal of the template after
      deposition leaves a regular hexagonal array of sphere segment pores where the
      depth of the pores and, thus, the topography of the surface are controlled by the
      thickness of gold deposited through the template. We find that, as the thickness
      of the porous film increases up to the radius of the pores, the apparent contact
      angle for water on the surface increases from 70 degrees on the flat surface to
      more that 130 degrees , and then with increasing thickness above the radius of
      the pores the apparent contact angle decreases back toward 70 degrees . We show
      that these changes in the apparent contact angle agree with the model of Cassie
      and Baxter for nonwetted surfaces even though the gold itself is hydrophilic. We
      also show that the apparent contact angle is independent of the diameter of the
      pores over the range 400-800 nm. This is the first reported example showing the
      change of a hydrophilic surface (theta; < 90 degrees ) into a hydrophobic surface
      (theta; > 90 degrees ) purely by control of the surface topography. The role of
      the pore shape and size in stabilizing the nonwetting (Cassie-Baxter) droplet on
      the surface is discussed.

PMID- 15723470
TI  - Behavior of oil droplets on an electrified solid metal surface immersed in ionic
      surfactant solutions.
AB  - The present study investigates the change in the shape of oil droplets immersed
      in an ionic surfactant solution when the droplets are in contact with metal
      surfaces to which an electrical potential is applied. The three-phase system of
      aqueous solution-oil-steel was subjected to low-voltage electric potentials,
      which resulted in sometimes dramatic changes in droplet shape and wetting. This
      electric potential was applied to the conductive steel surface directly, and the
      counter electrode was immersed in the solution. Changes in both the shape and
      wetting extent of hexadecane and phenylmethyl polysiloxane were observed for
      voltages between +/-3.0 V in both sodium dodecyl sulfate and cetyl
      trimethylammonium bromide solutions. The droplets' behavior was opposite to what
      would be expected for traditional electrowetting. In one instance, hexadecane
      droplets in sodium dodecyl sulfate solutions with a voltage of -3.0 V, a rapid
      and repeating droplet elongation and detachment was observed. Additionally, the
      impact of the observed phenomena on electrowetting enhanced ultrasonication is
      presented to demonstrate the potential improvements in industrial ultrasonic
      cleaning processes. The observations lead to the possibility of employing simple
      electrowetting techniques in the removal of oil from metal surfaces in a manner
      that could greatly improve the environmental and economic performance of aqueous
      cleaning techniques.

PMID- 15723471
TI  - Lamellar-to-cubic phase change in phospholipid bilayer systems incorporated with
      block copolymers: DMPC and PEO-PPO-PEO (P85).
AB  - We have used small-angle X-ray scattering and calorimetric methods to investigate
      the temperature-dependent phase behavior of ternary systems of phospholipid
      (DMPC), amphiphilic PEO-PPO-PEO block copolymer (Pluronics P85), and water. It is
      shown that a relatively small amount of block copolymers ( approximately 3 wt %)
      results in a lamellar-to-cubic phase transition. Still, both the bilayer
      characteristic main transition, associated with chain melting, and the
      pretransition, associated with in-plane modulations, are preserved for copolymer
      concentrations up to 50-70 wt %, indicating the preservation of a bilayer type of
      lipid organization also within the cubic phase. The main transition splits up
      into two transitions upon the addition of copolymers, one resembling the high
      cooperativity of the main transition and one broad transition which may reflect
      complex formation with the copolymers. Parallel studies incorporating
      poly(ethylene glycol) into the DMPC multilamellar vesicles do not give analogous
      structural changes. It is concluded that the major effect on the molecular scale
      of adding PEO-PPO-PEO block copolymers is not only due to the hydration of the
      membrane but also due to the incorporation of the PPO block into the bilayer
      structure.

PMID- 15723472
TI  - Spectroscopic study and local coordination of polyphosphate colloidal systems.
AB  - The interaction between metaphosphate chains and the metal ions Ca2+ and Eu3+ has
      been studied in water by Eu3+ luminescence, infrared absorption, and 31P NMR
      spectroscopy. Two main families of sites could be identified for the metal ions
      in the aqueous polyphosphate colloidal systems: (1) cagelike sites provided by
      the polyphosphate chain and (2) a family which arises following saturation of
      cagelike sites. Occupation of this second family leads to supramolecular
      interactions between polyphosphate chains and the consequent destabilization of
      the colloidal system. In the polyphosphate-Ca2+ system, this destabilization
      appears as a coacervation process. Equilibrium existing between colloidal species
      as a function of the compositions could be reasoned based on the spectroscopic
      measurements. The determination of coordination numbers and the correlation of
      the results with the observation of coacervates show that Eu3+ luminescence
      properties can be used to probe in a unique way the coacervation process.

PMID- 15723473
TI  - Evidence of multiple electrohydrodynamic forces acting on a colloidal particle
      near an electrode due to an alternating current electric field.
AB  - Total internal reflection microscopy was used to monitor the elevation of 4-7.5
      mum diameter particles near an electrode in response to an oscillating electric
      field with amplitude up to 8.5 kV/m. The media were 0.15 mM electrolyte solutions
      of HNO(3), NaHCO(3), and KOH, and the frequency band was 40 Hz to 10 kHz.
      Polystyrene-sulfonate particles were used in bicarbonate and KOH solutions, while
      polystyrene-amine particles were used in nitric acid. At frequencies less than
      500 Hz, large oscillations in elevation at the driving frequency with small
      superimposed Brownian excursions were observed. At frequencies above 1 kHz,
      deterministic oscillations in elevation were negligible compared to Brownian
      fluctuations, which allowed transformation of histograms of elevations into
      potential energy profiles. The ac field drew the particle closer on average to
      the electrode in KOH solutions (compared to the no-field average elevation) and
      the field pushed the particle farther from the electrode in NaHCO(3). In HNO(3) a
      reversal of average height was observed at a frequency of 300 Hz at 1.7 kV/m with
      the particle being drawn closer to the electrode at low frequencies and being
      pushed away at higher frequencies. The reversal reflects two different
      electrohydrodynamic mechanisms. Analysis of the data at a high frequency (10 kHz)
      revealed a net force that was attractive in KOH and repulsive in HNO(3). This net
      force scaled with E(2)omega(-)(1), where E is the amplitude and omega is the
      frequency.

PMID- 15723474
TI  - Aggregation phenomena on the ternary ionic-nonionic surfactant system:
      didodecyldimethylammonium bromide/octyl-beta-D-glucopyranoside/water. Mixed
      microaggregates, vesicles, and micelles.
AB  - The formation of a variety of mixed colloidal aggregates has been investigated on
      a ternary ionic-nonionic system constituted by (i) a double-chain cationic
      surfactant with a 12-carbon atom hydrophobic tail, didodecyldimethylammonium
      bromide (di-C(12)DMAB), (ii) a nonionic single-chain surfactant, octyl-beta-D
      glucopyranoside (OBG), and (iii) water. The study has been carried out by means
      of conductivity, zeta-potential, transmission electron microscopy (TEM), and
      cryogenic transmission electron microscopy (cryo-TEM) experiments on the highly
      diluted, very diluted, and moderately diluted regions. The formation of mixed
      microaggregates, prior to the appearance of mixed vesicles, has been undoubtly
      confirmed by conductivity, TEM, and zeta-potential results. The concentrations at
      which these mixed colloidal aggregates form, i.e., the mixed critical
      microaggregate concentration (CAC), the mixed critical vesicle concentration
      (CVC), and the mixed critical micelle concentration (CMC), have been determined
      from conductivity data, while the zeta-potential experiments allow for the
      characterization of the aggregate/solution interface. The shape and size of the
      microaggregates and vesicles have been evaluated from TEM and cryo-TEM
      micrographs, respectively. All of the experimental evidence has been also
      analyzed in terms of the theoretical packing parameter, P.

PMID- 15723475
TI  - Size fractionation in a phase-separated colloidal fluid.
AB  - Phase separation of a polydisperse colloidal dispersion implies size
      fractionation. An application of this effect is given by size-selective
      purification procedures associated with the colloidal synthesis of so-called
      monodisperse nanoparticles. We used electron microscopy to determine detailed
      particle size distributions of coexisting colloidal fluid phases containing
      highly polydisperse iron oxide nanoparticles with a log-normal distribution
      (sigma = 0.54 for the total system). Analysis of N approximately 10000 particles
      per phase yields the first five statistical moments of the distributions. Within
      experimental error, the interdependence of the statistical moments is in
      quantitative agreement with the "universal law of fractionation" proposed by
      Evans, Fairhurst, and Poon [Phys. Rev. Lett. 1998, 81, 1326], even though the
      theory was derived in the limit of slight polydispersity.

PMID- 15723476
TI  - Drying of films formed by ordered poly(ethylene oxide)-poly(propylene oxide)
      block copolymer gels.
AB  - The drying of hydrogel films formed by poly(ethylene oxide)-poly(propylene oxide)
      (PEO-PPO) block copolymers (Pluronic P105 and Pluronic L64) is investigated at
      various air relative humidity (RH) conditions in the range 11-94%. These
      amphiphilic block copolymers self-assemble to form a variety of ordered
      (lyotropic liquid crystalline) structures as the water content decreases. The
      amount of water lost increases linearly with the drying time initially (constant
      rate region, stage I). After this linear region, a falling rate is observed
      (stage II). The drying rate increases with decreasing RH, thus greatly shortening
      the drying time. A decrease of the initial film thickness or a decrease in the
      initial water content shortens the drying time; however, the drying mechanism
      remains the same. Analysis of the experimental data shows that the hydration
      level in the Pluronic hydrogel mainly determines the drying rate, rather than the
      type of ordered structure formed. Two distinct regions (liquid/gel and
      solid/crystalline) are observed in the drying isotherm for PEO-PPO block
      copolymers and homopolymer poly(ethylene glycol)s. A model for one-dimensional
      water diffusion is used to fit the experimental drying results at different RH,
      initial film thickness, and initial water content conditions. The model accounts
      for the shrinkage of the film during drying and for a water diffusion coefficient
      that is a function of the water concentration in the film. For the experimental
      conditions considered here, the Biot number (Bi) is less than unity and the
      drying is mainly limited by evaporation at the film surface. The diffusion model
      is used to obtain information for cases where Bi > 1.

PMID- 15723477
TI  - Analysis of the pressure-induced potential arising through composite membranes
      with selective surface layers.
AB  - When a pressure gradient is applied through a charged selective membrane, the
      transmembrane electrical potential difference, called the filtration potential,
      results from both the applied pressure and induced concentration difference
      across the membrane. In this work we investigate the electrokinetic properties
      relative to both active and support layers of a composite ceramic membrane close
      to the nanofiltration range. First, the volume charge density of the active layer
      is obtained by fitting a transport model to experimental rejection rates (which
      are controlled by the active layer only). Next, the value of the volume charge
      density is used to compute the theoretical filtration potential through the
      active layer. For sufficiently high permeate volume fluxes, the concentration
      difference across the active layer becomes constant, which allows assessing the
      membrane potential of the active layer. Experimental measurements of the overall
      filtration potential arising through the whole membrane are performed. The
      contribution of the support layer to this overall filtration potential is put in
      evidence. That implies that the membrane potential of the active layer cannot be
      deduced directly from the overall filtration potential measurements. Finally, the
      contribution of the support layer is singled out by subtracting the theoretical
      filtration potential of the active layer from the experimental filtration
      potential measured across the whole membrane (i.e., support + active layers). The
      amphoteric behavior of both layers is put in evidence, which is confirmed by
      electrophoretic measurements carried out with the powdered support layer and by
      recently reported tangential streaming potential measurements.

PMID- 15723478
TI  - Improvement of the Derjaguin-Broekhoff-de Boer theory for capillary
      condensation/evaporation of nitrogen in mesoporous systems and its implications
      for pore size analysis of MCM-41 silicas and related materials.
AB  - In this work, we propose an improvement of the classical Derjaguin-Broekhoff-de
      Boer (DBdB) theory for capillary condensation/evaporation in mesoporous systems.
      The primary idea of this improvement is to employ the Gibbs-Tolman-Koenig-Buff
      equation to predict the surface tension changes in mesopores. In addition, the
      statistical film thickness (so-called t-curve) evaluated accurately on the basis
      of the adsorption isotherms measured for the MCM-41 materials is used instead of
      the originally proposed t-curve (to take into account the excess of the chemical
      potential due to the surface forces). It is shown that the aforementioned
      modifications of the original DBdB theory have significant implications for the
      pore size analysis of mesoporous solids. To verify our improvement of the DBdB
      pore size analysis method (IDBdB), a series of the calcined MCM-41 samples, which
      are well-defined materials with hexagonally ordered cylindrical mesopores, were
      used for the evaluation of the pore size distributions. The correlation of the
      IDBdB method with the empirically calibrated Kruk-Jaroniec-Sayari (KJS)
      relationship is very good in the range of small mesopores. So, a major advantage
      of the IDBdB method is its applicability for small mesopores as well as for the
      mesopore range beyond that established by the KJS calibration, i.e., for mesopore
      radii greater than approximately 4.5 nm. The comparison of the IDBdB results with
      experimental data reported by Kruk and Jaroniec for capillary
      condensation/evaporation as well as with the results from nonlocal density
      functional theory developed by Neimark et al. clearly justifies our approach.
      Note that the proposed improvement of the classical DBdB method preserves its
      original simplicity and simultaneously ensures a significant improvement of the
      pore size analysis, which is confirmed by the independent estimation of the mean
      pore size by the powder X-ray diffraction method.

PMID- 15723479
TI  - Silica surfaces lubrication by hydrated cations adsorption from electrolyte
      solutions.
AB  - Adsorption of hydrated cations on hydrophilic surfaces has been related to a
      variety of phenomena associated with the short-range interaction forces and
      mechanisms of the adhesive contact between the surfaces. Here we have
      investigated the effect of the adsorption of cations on the lateral interaction.
      Using lateral force microscopy (LFM), we have measured the friction force between
      a silica particle and silica wafer in pure water and in electrolyte solutions of
      LiCl, NaCl, and CsCl salts. A significant lubrication effect was demonstrated for
      solutions of high electrolyte concentrations. It was found that the adsorbed
      layers of smaller and more hydrated cations have a higher lubrication capacity
      than the layers of larger and less hydrated cations. Additionally, we have
      demonstrated a characteristic dependence of the friction force on the sliding
      velocity of surfaces. A mechanism for the observed phenomena based on the
      microstructures of the adsorbed layers is proposed.

PMID- 15723480
TI  - Nanostructure of a "carpet"-like dense layer/polyelectrolyte brush layer in a
      block copolymer monolayer at the air-water interface.
AB  - The "carpet"/brush double layer structure in the polyelectrolyte layer in the
      amphiphilic diblock copolymer monolayer at the air-water interface was
      quantitatively studied by in situ neutron reflectometry in addition to X-ray
      reflectivity measurements. As a result of the higher contrast between
      polyelectrolyte [poly(methacrylic acid)] and solvent (D(2)O) for the neutron, the
      brush structure could be estimated more accurately as a function of surface
      pressure, that is, brush density. The thickness of the carpet layer, which is
      thought to be formed to reduce the interfacial free energy between water and the
      hydrophobic layer, was almost constant at 10-20 A at any surface pressure
      studied. Growth was clearly observed in the whole brush length with increasing
      surface pressure, and it was estimated to be almost 60% of the full-stretch
      length of the ionic polymer chain. Furthermore, by the comparison of density
      profiles by neutron and X-ray reflectometry, an anomalous hydration was
      suggested.

PMID- 15723481
TI  - Self-assembled silane monolayers: fabrication with nanoscale uniformity.
AB  - Illustrating direct connections between surface chemical events and mechanical
      and topological characteristics of self-assembled monolayers derived from
      octadecyltrichlorosilane (OTS) adsorption on Si(100), layers prepared in the
      presence and absence of moisture have been characterized. Uniform and robust self
      assembled monolayers are demonstrated provided the Si(100) surface is fully
      hydroxylated by treatment in piranha solution and the dried surface is exposed to
      OTS under strict anhydrous conditions. With nanoscale resolution, the uniform
      mechanical properties are confirmed by interfacial force microscopy while the
      uniform topological properties are evident in atomic force microscopy images. The
      monolayer character of the OTS coverage is confirmed by X-ray photoelectron
      spectroscopy, ellipsometry, and patterning experiments. Analogous surfaces,
      prepared in the presence of moisture, exhibit nonuniform topological and
      mechanical properties.

PMID- 15723482
TI  - Bioreactive surfaces prepared via the self-assembly of dendron thiols and
      subsequent dendrimer bridging reactions.
AB  - Here, we report a novel route to prepare bioreactive surfaces on gold by the self
      assembly of generation-three hydroxyl-terminated dendron thiols (G3-OH) and
      subsequent bridging reactions using generation-two amine-terminated dendrimers
      (G2-NH(2)). It has been shown that G3-OH dendron thiols form a stable and uniform
      self-assembled monolayer on gold, which can be activated by the homobifunctional
      cross-linker N,N-disuccinimidyl carbonate (DSC). Subsequent derivatization of the
      activated monolayer via dendrimer bridging reactions with G2-NH(2) enhances the
      stability, reactivity, and versatility of the prepared surface. Each step of the
      surface formation reaction has been monitored, and the resulting surface has been
      characterized by wetting, electrochemistry, scanning tunneling microscopy (STM),
      and infrared (IR) spectroscopy measurements. The reactivity of this surface was
      demonstrated by a Schiff base coupling reaction with 4-cyanobenzaldehyde, by
      immobilizing biotin molecules onto the peripheral amine groups using one of the
      conjugation methods, and by further binding avidin onto the biotinylated surface.
      We believe that the prepared bioreactive surface with a high density of amine
      groups will be useful for the immobilization of biological macromolecules for
      various biosensor applications, such as the fabrication of DNA microarrays and
      protein chips.

PMID- 15723483
TI  - Surface reactions of 1-propanethiol on GaAs(100).
AB  - The adsorption and decomposition pathways of 1-propanethiol on a Ga-rich
      GaAs(100) surface have been investigated using the techniques of temperature
      programmed desorption, X-ray photoelectron spectroscopy (XPS), and time-of-flight
      secondary ion mass spectrometry (TOF-SIMS). 1-Propanethiol adsorbs dissociatively
      on a clean GaAs(100) surface to form propanethiolate and hydrogen. Further
      reactions of these species to form new products compete with the recombinative
      desorption of molecular propanethiol. The C-S bond scission in the
      propanethiolate results in the formation of propyl species and elemental sulfur.
      The generation of propene via beta-hydride elimination then follows. In addition,
      propane and hydrogen form via reductive elimination processes. A recombinative
      high-temperature propanethiol desorption state is also observed. XPS and TOF-SIMS
      analyses confirm the presence of sulfur on the GaAs(100) surface following
      thermal decomposition. This paper discusses the mechanisms by which these
      products form on the GaAs(100) surface.

PMID- 15723484
TI  - Forces between silica surfaces with adsorbed cationic surfactants: influence of
      salt and added nonionic surfactants.
AB  - Forces have been measured between silica surfaces with adsorbed surfactants by
      means of a bimorph surface force apparatus. The surfactants used are the cationic
      surfactant tetradecyltrimethylammonium bromide (TTAB) and the nonionic surfactant
      hexakis(ethylene glycol) mono-n-tetradecyl ether (C(14)E(6)) as well as mixtures
      of these two surfactants. The measurements were made at elevated pH, and the
      effect of salt was studied. At high pH the glass surface is highly charged, which
      increases the adsorption of TTAB. Despite the low adsorption generally seen for
      nonionic surfactants on silica at high pH, addition of C(14)E(6) has a
      considerable effect on the surface forces between two glass surfaces in a TTAB
      solution. The barrier force is hardly affected, but the adhesion is reduced
      remarkably. Also, addition of salt decreases the adhesion, but increases the
      barrier force. In the presence of salt, addition of C(14)E(6) also increases the
      thickness of the adsorbed layer. The force barrier height is also shown to be
      related to literature values for surface pressure data in these systems.

PMID- 15723485
TI  - Kinetics of film formation by interfacial polycondensation.
AB  - An approximate analytical model of film formation by interfacial polycondensation
      is presented. The analysis requires knowledge of a minimal set of certain kinetic
      parameters (monomer diffusivities and reaction rate constants) and reaction
      conditions (monomer concentrations and thickness of the unstirred layer). The
      process proceeds as a succession of two or three markedly different kinetic
      regimes. Each regime (insipient film formation, slowdown, and diffusion-limited
      growth) sets a different pattern of local polymer accumulation, with important
      implications for the structure of the emerging film. At the incipient stage, a
      loose polymer film begins to emerge in a fixed narrow region inside the boundary
      layer, followed by gradual densification of the middle part of the film. A
      condition for film formation is thus formulated on the basis of our analysis. The
      model predicts that two different scenarios are possible, which depend on the
      permeability of the polymer: films with a low permeability to both monomers pass
      through an abrupt slowdown of film growth, whereas permeable films undergo a
      smooth transition between the incipient film formation and diffusion-limited
      regimes. The model incorporates the highly important effects of the accumulation
      of reactive end groups and the decrease of monomer diffusion with the polymer
      concentration on the kinetics of the process and film characteristics. In
      addition, the validity of the utilized mean-field approach is analyzed, and the
      analysis suggests a direct correlation between the roughness and the thickness of
      the film. The results are in good agreement with an earlier numerical study and
      the direct structural studies of polyamide membrane films.

PMID- 15723486
TI  - Liquid ring formation from contacting, nonmiscible sessile drops.
AB  - When two pure and nonmiscible liquid drops at rest on a rigid substrate come into
      close contact with a quasi-zero spreading velocity, one of them may be sucked
      around the second into a liquid ring, leading in some cases to the complete
      engulfment of the latter. We here show that the conditions for this amazing and
      unusual capillary effect to develop are defined by two sets of criteria: the
      "reciprocal" spreading of one drop with respect to the other and a "geometrical
      wetting" criterion related to the opening of the groovelike channels along the
      base of the attracting drop. Despite the exceeding simplicity and roughness of
      liquid drops as compared to living cells, the phenomenon strangely recalls, at
      least in its mechanistic aspect, the fundamental biological process of
      phagocytosis. Besides these fundamental aspects, this effect may also have
      interesting implications for microstructuring techniques.

PMID- 15723487
TI  - Surface complexation of DNA with insoluble monolayers. Influence of divalent
      counterions.
AB  - DNA interacts with insoluble monolayers made of cationic amphiphiles as well as
      with monolayers of zwitterionic lipids in the presence of divalent ions. Binding
      to dioctadecyldimethylammonium bromide (DODAB) or distearoyl-sn-glycero-3
      phosphocholine (DSPC) monolayers in the presence of calcium is accompanied by
      monolayer expansion. For the positively charged DODAB monolayer, this causes a
      decrease of surface potential, while an increase is observed for the DSPC
      monolayers. Binding to dipalmitoyl-sn-glycero-3-phosphocholine preserves most of
      the liquid expanded-liquid condensed coexistence region. The liquid condensed
      domains adopt an elongated morphology in the presence of DNA, especially in the
      presence of calcium. The interaction of DNA with phospholipid monolayers is ion
      specific: the presence of calcium leads to a stronger interaction than magnesium
      and barium. These results were confirmed by bulk complexation studies.

PMID- 15723488
TI  - Blends of amphiphilic trisilanolisobutyl-POSS and phosphine oxide substituted
      poly(dimethylsiloxane) at the air/water interface.
AB  - Mixtures of a polyhedral oligomeric silsesquioxane, trisilanolisobutyl-POSS, and
      a polar silicone, poly(dimethyl-co-methylvinyl-co-methyl, 2-diphenyl phosphine
      oxide ethyl) siloxane (PDMS-PO), spread as Langmuir monolayers at the air/water
      interface are used to examine the surface phase behavior and aggregation of
      trisilanolisobutyl-POSS as a function of silicone composition. Analyses of the
      surface pressure-area per monomer (Pi-A) isotherms in terms of the collapse
      pressures and excess Gibbs free energies of mixing indicate the monolayers form
      slightly negative deviation mixtures. Direct observations of surface morphology
      with Brewster angle microscopy in the collapsed regime reveal that the governing
      factor for aggregation is the collapse Pi of the component with a stronger
      affinity for water. In trisilanolisobutyl-POSS/PDMS-PO blends, POSS aggregates as
      discrete domains and does not coalesce into larger aggregates or networklike
      structures for <80 wt % POSS, a feature that is vastly different from a previous
      study of POSS blended with regular poly(dimethylsiloxane).

PMID- 15723489
TI  - Preparation, characterization, and heck reaction of siloxane films derived from
      carbosilane dendrons with a bromophenyl group at the focal point and up to 27
      SiCl3 groups at the periphery.
AB  - Multidentate organosiloxane thin films were prepared on SiO2/Si surfaces by
      solution phase deposition of carbosilane dendrons containing a bromophenyl group
      at the focal point and 3 (Br-G0), 9 (Br-G1), and 27 (Br-G2) SiCl3 groups at the
      periphery. The films were characterized by contact angle goniometry,
      ellipsometry, and X-ray photoelectron spectroscopy (XPS). The results indicated
      that about six Br-G0 molecules covered the same surface area as three Br-G1
      molecules and one Br-G2 molecule. Hence, the density of the bromophenyl groups in
      the films could be defined by the size (generation) of the dendron adsorbates. We
      also demonstrated that the bromophenyl groups on the film surfaces could serve as
      a handle for attaching conjugated molecules via formation of C-C bonds. Thus,
      upon treatment of the films with 4-fluorostyrene under Heck reaction conditions,
      XPS analysis showed that about 90, 66, and 51% of the bromine atoms in the films
      prepared from Br-G0, Br-G1, and Br-G2 were consumed, and 94, 82, and 58% of the
      consumed bromine atoms were replaced by fluorostyryl groups. The remaining
      bromophenyl groups were probably not accessible to the reactants because of their
      unfavorable orientation. The overall yields for the surface Heck reaction were
      estimated to be 84, 54, and 30% for the films prepared from Br-G0, Br-G1, and Br
      G2, respectively.

PMID- 15723491
TI  - Determination of nanocrystal sizes: a comparison of TEM, SAXS, and XRD studies of
      highly monodisperse CoPt3 particles.
AB  - One of the most fundamental tasks in nanoscience is the accurate determination of
      particle sizes. Various methods have been developed to elucidate the mean
      particle diameter and the standard deviation for an ensemble of nanocrystals.
      However, good agreement between the results from different methods is not always
      encountered in the literature. In this study, we investigate colloidally
      prepared, highly monodisperse CoPt3 nanoparticles by transmission electron
      microscopy (TEM), small-angle X-ray scattering (SAXS), and powder X-ray
      diffraction (XRD). The results are compared in order to examine to which extent
      agreement is obtained by the different techniques when applied to small
      nanocrystals in the size range below 10 nm. In particular, the applicability of
      the simple Scherrer formula for size determination from the broadening of XRD
      reflections is checked. When the different techniques are correctly applied, the
      results from all methods are in good agreement.

PMID- 15723490
TI  - Models of pesticides inside cavities of molecular dimensions. A role of the guest
      inclusion in the dechlorination process.
AB  - The reduction mechanism of the pesticide vinclozoline (3-(3,5-dichlorophenyl)-5
      methyl-5-vinyl-1,3-oxazolidine-2,4-dione) was studied in nonaqueous solvents in
      the confined environment of a cyclodextrin (CD) cavity. The effect of the cavity
      dimensions on the mechanism of the redox process was evaluated using glucose as a
      reference and using three cyclodextrin molecules of different cavity sizes,
      namely, alphaCD, betaCD, and gammaCD. In the absence of CD the main reduction
      product of vinclozoline in the first reduction step is dichloroaniline. An
      addition of glucose leads to a quantitative change of mechanism with 10 products
      in total. Addition of CD, however, leads exclusively to dechlorination of the
      phenyl ring. The degree of dechlorination depends strongly on the choice of
      cyclodextrin molecule. The importance of the complex formation equilibria in the
      change of the mechanism is supported by a series of semiempirical AM1 quantum
      mechanical calculations. Very good correlation (correlation coefficient 0.995)
      was obtained between the complex stabilization energy of the inclusion complex
      and the degree of pesticide dechlorination. Additionally, we were able to show
      that the complexes are stabilized by the formation of intermolecular hydrogen
      bonds between the host and guest species. CD molecules do not simply act as
      proton donors in a nonaqueous environment, but also protect parts of the molecule
      included within the cavity and steer the degradation process toward fewer
      products.

PMID- 15723492
TI  - Two-potential electrochemical probe for study of DNA immobilization.
AB  - A two-potential electrochemical method is applied to study DNA immobilization, by
      the simultaneous characterization of capture probe DNA self-assembled monolayers
      and hybridized target DNA molecules on a given gold electrode surface. Capture
      probe and target DNA strands are labeled with ferrocenes composed of differing
      chemical environments, to permit their simultaneous, yet independent signaling at
      different formal potentials, so that their respective signals may be de
      convoluted and assessed for relative surface concentration. Some special
      attributes of the nondestructive two-potential electrochemical probe described
      herein include surface sensitivity, chemical and orientation specificity, and the
      ability to provide a real-time, in situ probe that does not need any wash steps
      for stringency. This electrochemical probe is applied to study the kinetics,
      surface architecture, coverage, and orientation of DNA during its immobilization
      on gold. On the basis of our results primarily from this electrochemical probe,
      and validated by N(1s) core-level X-ray photoelectron spectra, we judge
      significant DNA deposition within 5 min of incubation in the deposition
      solutions, with the capture probe DNA anchored predominantly via the thiol end,
      even at low coverages. Surface coverage for DNA immobilization plateaus within 30
      min of incubation time to approximately 2 x 10(13) molecules/cm(2) and the
      immobilization kinetics as determined from this electrochemical method are
      consistent with surface re-organization as the rate-determining step.

PMID- 15723493
TI  - In-situ scanning tunneling microscopy of carbon monoxide adsorbed on Au(111)
      electrode.
AB  - In-situ scanning tunneling microscopy (STM) coupled with cyclic voltammetry was
      used to examine the adsorption of carbon monoxide (CO) molecules on an ordered
      Au(111) electrode in 0.1 M HClO4. Molecular resolution STM revealed the formation
      of several commensurate CO adlattices, but the (9 x radical 3) structure
      eventually prevailed with time. The CO adlayer was completely electrooxidized to
      CO2 at 0.9 V versus RHE in CO-free 0.1 M HClO(4), as indicated by a broad and
      irreversible anodic peak which appeared at this potential in a positive potential
      sweep from 0.05 to 1.6 V. A maximal coverage of 0.3 was estimated for CO
      admolecules from the amount of charge involved in this feature. Real-time in-situ
      STM imaging allowed direct visualization of the adsorption process of CO on
      Au(111) at 0.1 V, showing the lifting of (radical 3 x 22) reconstruction of
      Au(111) and the formation of ordered CO adlattices. The (9 x radical 3) structure
      observed in CO-saturated perchloric acid has a coverage of 0.28, which is
      approximately equal to that determined from coulometry. Switching the potential
      from 0.1 to -0.1 V restored the reconstructed Au(111) with no change in the (9 x
      radical 3)-CO adlattice. However, the reconstructed Au(111) featured a pairwise
      corrugation pattern with two nearest pairs separated by 74 +/- 1 A, corresponding
      to a 14% increase from the ideal value of 65.6 A known for the ( radical 3 x 22)
      reconstruction. Molecular resolution STM further revealed that protrusions
      resulting from CO admolecules in the (9 x radical 3) structure exhibited
      distinctly different corrugation heights, suggesting that the CO molecules
      resided at different sites on Au(111). This ordered structure predominated in the
      potential range between 0.1 and 0.7 V; however, it was converted into new
      structures of (7 x radical 7) and ( radical 43 x 2 radical 13) on the
      unreconstructed Au(111) when the potential was held at 0.8 V for ca. 60 min. The
      coverage of CO adlayer decreased accordingly from 0.28 to 0.13 before it was
      completely removed from the Au(111) surface at more positive potentials.

PMID- 15723494
TI  - Surface characterization of the extracellular matrix remaining after cell
      detachment from a thermoresponsive polymer.
AB  - The temperature-responsive behavior of poly(N-isopropyl acrylamide) (pNIPAM)
      directly affects the attachment and detachment of cells cultured on these
      surfaces. At culture temperatures, cells behave similarly to those on tissue
      culture polystyrene (TCPS), while at room temperature, cells cultured on pNIPAM
      spontaneously detach as a confluent sheet. In comparison, cells grown on TCPS
      remain attached indefinitely after the temperature drop, requiring enzymatic or
      mechanical removal. In this work, we present an examination of the response of
      bovine aortic endothelial cells (BAECs) and extracellular matrix (ECM) proteins
      to plasma polymerized NIPAM (ppNIPAM) surfaces using X-ray photoelectron
      spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS),
      and immunostaining. Immunoassay results reveal that, although fibronectin,
      laminin, and collagen closely associate with the cell sheet, some collagen may be
      associated with the surface, as well. Our XPS results indicate that ppNIPAM
      surfaces after cell liftoff differ from their blank counterparts, the primary
      distinction being the presence of amide and alcohol species on ppNIPAM surfaces
      used for cell culture, possibly owing to the presence of a proteinaceous film.
      Finally, a comparison between ppNIPAM-treated surfaces used for cell culture
      versus control surfaces by principal component analysis of the ToF-SIMS data
      confirms that the surfaces differ; the presence of molecular ion fragments from
      amino acids (e.g., alanine, glycine, and proline) is the chief reason for this
      difference. Therefore, from our surface characterization of ppNIPAM-coated TCPS
      after cell liftoff, we conclude that although low-temperature liftoff of the BAEC
      monolayer is accompanied by the majority of the components of the ECM, some of
      the ECM proteins still remain at the surface.

PMID- 15723495
TI  - Characterization of grafting density and binding efficiency of DNA and proteins
      on gold surfaces.
AB  - The surface grafting density of biomolecules is an important factor for
      quantitative assays using a wide range of biological sensors. We use a
      fluorescent measurement technique to characterize the immobilization density of
      thiolated probe DNA on gold and hybridization efficiency of target DNA as a
      function of oligonucleotide length and salt concentration. The results indicate
      the dominance of osmotic and hydration forces in different regimes of salt
      concentration, which was used to validate previous simulations and to optimize
      the performance of surface-stress based microcantilever biosensors. The
      difference in hybridization density between complementary and mismatched target
      sequences was also measured to understand the response of these sensors in base
      pair mismatch detection experiments. Finally, two different techniques for
      immobilizing proteins on gold were considered and the surface densities obtained
      in both cases were compared.

PMID- 15723496
TI  - Automated, high-resolution micropipet aspiration reveals new insight into the
      physical properties of fluid membranes.
AB  - We describe recent advances in our experimental approach to examine the physical
      properties of biological and artificial membranes by automated micropipet
      aspiration. New instrumentation allows us to apply fast yet precise tension
      protocols to membranes while continuously recording the membrane deformation with
      high-speed videomicroscopy. Robust algorithms for subpixel geometric measurements
      track the displacements of membrane edges with resolution of a few nanometers and
      enable us to determine changes of the membrane area and enclosed volume of pipet
      aspirated cells or vesicles with exceptional accuracy. Experimentation and data
      analysis are greatly facilitated by custom-written software whose basic design is
      described here as well. Example measurements demonstrate how this technique has
      significantly improved the amount and reliability of data obtained by various
      types of micropipet-aspiration experiments, allowing us to study interesting
      aspects of membrane behavior that have eluded earlier techniques.

PMID- 15723498
TI  - Voltage-tunable volume transitions in nanoscale films of poly(hydroxyethyl
      methacrylate) surfaces grafted onto gold.
AB  - Surface grafting of a polymerizable monomer onto Au was used to produce nanometer
      scale planar hydrogel films with controllable volume. A self-assembled monolayer
      of 11-mercaptoundecanoic acid on a planar Au surface was activated through water
      soluble carbodiimide and N-hyroxysuccinimide followed by reaction with 2
      aminomethacrylate to produce a methacrylate-terminated surface layer, which
      readily polymerized under UV radiation in the presence of hydroxyethyl
      methacrylate monomer, ethylene glycol dimethacrylate cross-linker, and a
      photoinitiator. The reaction steps were characterized by external reflection mode
      Fourier transform IR spectroscopy. Under controlled UV exposure, thin (3 nm < d <
      10 nm) hydrogel films were obtained from 1:1 ethanol/H(2)O. Surface plasmon
      resonance measurements were used to characterize both the synthesis of the
      hydrogel and the potential-induced volume changes. The nanometer-scale hydrogels
      thus produced undergo reproducible changes in thickness, when a potential is
      applied across the film. Thickness changes increasing with applied potential were
      obtained for both voltages in the range |V(appl)| </= 600 mV. In NaCl,
      electrolyte films swell with application of negative potentials and shrink with
      positive potentials, due to the imbibing or extrusion of hydrated Na(+) ions,
      respectively. Thickness changes as large as 50% can be achieved. An increase in
      the cross-linker content results in thicker films, but at the cost of
      dramatically restricted swelling. Response times are generally faster for smaller
      applied potentials, as expected if the volume change results from mass transport
      of electrolyte.

PMID- 15723497
TI  - Hybridization with nanostructures of single-stranded DNA.
AB  - Nanostructures of single-stranded DNA (ssDNA) were produced within alkanethiol
      self-assembled monolayers using nanografting, an atomic force microscopy (AFM)
      based lithography technique. Next, variations of the fabrication parameters, such
      as the concentration of ssDNA or lines per frame, allowed for the regulation of
      the density of ssDNA molecules within the nanostructures. The label-free
      hybridization of nanostructures, monitored using high-resolution AFM imaging, has
      proven to be highly selective and sensitive; as few as 50 molecules can be
      detected. The efficiency of the hybridization reaction at the nanometer scale
      highly depends on the ssDNA packing density within the nanostructures. This
      investigation provides a fundamental step toward sensitive DNA detection and
      construction of complex DNA architectures on surfaces.

PMID- 15723499
TI  - Self-assembled monolayers of dendron thiols for electrodeposition of gold
      nanostructures: toward fabrication of superhydrophobic/superhydrophilic surfaces
      and pH-responsive surfaces.
AB  - This paper describes the fabrication of surfaces with different wettability,
      superhydrophobic/superhydrophilic, and pH-responsive properties. We used a self
      assembled monolayer (SAM) of a dendron thiol as the underlying surface for
      electrodeposition of gold nanostructures. After this modification with a SAM of n
      dodecanethiol or 11-mercaptoundecanol, the surface shows remarkable
      superhydrophobic properties with a contact angle of about 155 degrees and a tilt
      angle of less than 2 degrees or superhydrophilic properties with a contact angle
      of about 0 degrees , respectively. Moreover, a large-scale pH-responsive surface
      was obtained by modification with 2-(11-mercaptoundecanamido)benzoic acid (7)
      (MUABA). The pH-responsive behavior was amplified by using rough surfaces.

PMID- 15723500
TI  - Ultrathin coatings from isocyanate-terminated star PEG prepolymers: layer
      formation and characterization.
AB  - In this study we present the preparation of thin and ultrathin coatings from six
      arm star-shaped isocyanate-terminated prepolymers on amino-functionalized silicon
      wafers. The backbone of the stars is a statistical copolymer of ethylene oxide
      and propylene oxide in the ratio 80:20 (Star PEG). Film preparation by spin
      coating from aqueous THF resulted in a variety of film morphologies that are
      determined by the water content of the solvent. Water is indispensable for
      activation of the isocyanate-terminated stars in solution and for proper cross
      linking of the coatings on the substrate. This cross-linking results in a dense
      network of PEG chains on the substrate linked via urea groups with a mesh size of
      the network that corresponds to the arm length of the stars. Layer thickness
      variations between 3 and 500 nm revealed a strong dependence of the contact angle
      with water on the layer thickness which is explained by the chemical composition
      of the coatings. Due to the high functionality of the star-shaped prepolymers,
      free amino groups remain in the films that were detected by fluorescence
      microscopy after reaction with 4-chloro-7-nitrobenzofurazan (NBF). To test the
      system for the ability to prevent unspecific interaction with proteins,
      adsorption of fluorescence-labeled avidin was examined with fluorescence
      microscopy. For layer thicknesses between 3 and 50 nm, no protein adsorption
      could be detected.

PMID- 15723501
TI  - Simulation and investigation of factors affecting high aspect ratio UV embossing.
AB  - UV embossing is a replication method whereby an UV-curable polymer is pressed
      against a patterned mold and cured with UV irradiation, resulting in a patterned
      polymeric substrate. High aspect ratio UV embossing will find diverse
      applications in tissue engineering, micro-optics, display technologies, and
      sensors. Demolding of an UV-embossed polymer pattern with aspect ratio of 5 from
      the mold has previously been demonstrated experimentally. In this paper,
      parameters that affect the demolding process have been identified and
      investigated. They include cross-linking shrinkage during curing by UV
      irradiation, modulus of cured polymer, interfacial fracture strength and
      toughness, and loading method during demolding. Shrinkage is an important
      parameter, and an optimum level of shrinkage to avoid breakage of the embossing
      during demolding was found to exist. This optimum level is that at which the
      maximum stress (sigma(1)max) experienced by the polymer during demolding is
      minimized. The micromechanics of demolding was found to be different for
      shrinkage values lower or larger than the optimum value.

PMID- 15723502
TI  - Direct conjugation of semiconductor nanoparticles with proteins.
AB  - Nanocrystalline CdS particles directly conjugated with bovine serum albumin (BSA)
      protein were prepared by applying the supercritical fluid processing technique,
      rapid expansion of a supercritical solution into a liquid solvent. The direct
      conjugation takes advantage of the unique features of the process for
      nanoparticle formation. The BSA-conjugated CdS nanoparticles in stable aqueous
      suspension or in the solid state were characterized by using microscopy, X-ray
      diffraction, and optical spectroscopy methods. The results show that well
      dispersed CdS nanoparticles are coated with BSA in a core-shell-like arrangement
      and that the protein species associated with the nanoparticles remain functional
      according to the modified Lowry assay. These BSA-conjugated CdS nanoparticles are
      also strongly luminescent, with the luminescence spectrum contributed to
      primarily by the exciton emission.

PMID- 15723503
TI  - Synthesis of branched gold nanocrystals by a seeding growth approach.
AB  - Synthesis of branched gold nanocrystals by a seeding growth approach is
      described. In this process, HAuCl4 aqueous solution was supplied stepwise to grow
      the gold seeds (approximately 2.5 nm) into larger nanoparticles with a highly
      faceted particle structure (approximately 15-20 nm in diameter). Sodium dodecyl
      sulfate (SDS) served as a capping agent to facilitate the formation of highly
      faceted nanoparticles, and ascorbic acid was used as a weak reducing agent. The
      highly faceted nanoparticles then transformed into branched nanocrystals
      (approximately 40 nm in length) by further addition of the SDS-HAuCl4 solution
      and ascorbic acid for particle growth. The branched nanocrystals show bipod,
      tripod, tetrapod, and pentapod structures and are composed of mainly (111)
      lattice planes. These multipods appear to grow along the twin boundaries of the
      initially formed highly faceted gold nanoparticles, as the twin boundaries on the
      pods originate from the centers of the branched nanocrystals. The concentration
      of ascorbate ions in the solution was found to have a profound influence on
      branch formation. These branched nanocrystals are stable to storage at low
      temperature (that is, 4 degrees C), but they may slowly evolve into a
      multitwinned faceted crystal structure (that is, pentagonal-shaped decahedral
      structure) when stored at 30 degrees C.

PMID- 15723504
TI  - Ordered honeycomb-structured gold nanoparticle films with changeable pore
      morphology: from circle to ellipse.
AB  - Two-dimensionally ordered honeycomb structures have been prepared on
      dodecanethiol-capped gold nanoparticle films by blowing moist air across the
      surface of the nanoparticle solution. The pore morphology can be altered from
      circle to ellipse with tunable aspect ratios by carefully controlling the
      direction and velocity of airflow. The formation mechanisms of different surface
      morphologies have been discussed in terms of the surface and interfacial tension.

PMID- 15723505
TI  - pH-triggered assembly of gold nanorods.
AB  - The self-assembly of surfactant-protected gold nanorods (aspect ratio 3.3 +/-
      0.3, 20.6 +/- 5.5 nm width, and 67.5 +/- 9.0 nm length) into ordered structures
      using adipic acid is presented. As made, the gold nanorods are coated with
      cationic surfactant, which gives them a net positive charge in aqueous solution.
      The pH-dependent assembly is directed by electrostatic interactions between the
      positively charged nanorods and negatively charged, deprotonated adipic acid.
      Absorption spectra and light scattering measurements of these nanorods suggest
      that aggregation is initiated in solution in the presence of adipic acid at pH 7
      8, but not at pH 3, to form small assemblies of nanorods. Zeta potential
      measurements show that the assembly is significantly less positively charged in
      the presence of deprotonated adipic acid than when adipic acid is fully
      protonated.

PMID- 15723506
TI  - Effect of colloidal nanocatalysis on the metallic nanoparticle shape: the Suzuki
      reaction.
AB  - Dominantly tetrahedral shaped poly(vinylpyrrolidone)-platinum (PVP-Pt)
      nanoparticles are shown to catalyze the Suzuki reaction between phenylboronic
      acid and iodobenzene but are not as active as the spherical palladium
      nanoparticles studied previously. The dominantly tetrahedral PVP-Pt nanoparticles
      (55 +/- 4% regular tetrahedral, 22 +/- 2% distorted tetrahedral, and 23 +/- 2%
      spherical nanoparticles) are synthesized by using the hydrogen reduction method.
      The transmission electron microscopy (TEM) results show that a transformation of
      shape from tetrahedral to spherical Pt nanoparticles takes place 3 h into the
      first cycle of the reaction. After the first cycle, the spherical nanoparticles
      have a similar size distribution to that of the tetrahedral nanoparticles before
      the reaction and the observed shape distribution is 18 +/-6% regular tetrahedral,
      28 +/- 5% distorted tetrahedral, and 54 +/- 5% spherical nanoparticles. After the
      second cycle of the Suzuki reaction, the shape distribution is 13 +/- 5% regular
      tetrahedral, 24 +/- 5% distorted tetrahedral, and 63 +/- 7% spherical
      nanoparticles. After the second cycle, the transformed spherical nanoparticles
      continue to grow, and this could be due to the strong capping action of the
      higher molecular weight PVP (M(w) = 360 000), which makes the nanoparticles more
      resistant to aggregation and precipitation, unlike the Pd nanoparticles capped
      with the lower molecular weight PVP (M(w) = 40 000) used previously. The
      transformation in shape also occurs when the nanoparticles are refluxed in the
      presence of the solvent, sodium acetate, and iodobenzene and results in spherical
      nanoparticles with a similar size distribution to that of the tetrahedral
      nanoparticles before any perturbations. However, in the presence of phenylboronic
      acid, the regular tetrahedral nanoparticles remain dominant (51 +/- 6%) and
      maintain their size. These results support our previous studies in which we
      proposed that phenylboronic acid binds to the nanoparticle surface and thus acts
      as a capping agent for the particle and reacts with the iodobenzene. Recycling
      the nanoparticles results in a drastic reduction of the catalytic activity, and
      this must be due to the transformation of shape from the dominantly tetrahedral
      to the larger dominantly spherical nanoparticles. This also supports results in
      the literature that show that spherical platinum nanoparticles do not catalyze
      this reaction.

PMID- 15723507
TI  - Magnetic alignment of the chiral nematic phase of a cellulose microfibril
      suspension.
AB  - Stable suspensions of tunicate cellulose microfibrils were prepared by acid
      hydrolysis of the cellulosic mantles of tunicin. They formed a chiral nematic
      phase above a critical concentration. External magnetic fields were applied to
      the chiral nematic phase in two different manners to control its phase structure.
      (i) Static magnetic fields ranging 1-28 T were used to align the chiral nematic
      axis (helical axis) in the field direction. (ii) A rotating magnetic field (5 T,
      10 rpm) was applied to unwind the helices and to form a nematic phase. These
      phenomena were interpreted in terms of the anisotropic diamagnetic susceptibility
      of the cellulose microfibril. The diamagnetic susceptibility of the microfibril
      is smaller in the direction parallel (chi( parallel)) to the fiber axis than in
      the direction perpendicular (chi( perpendicular)) to the fiber axis, that is,
      chi( parallel) < chi( perpendicular) < 0. Because the helical axis coincides with
      the direction normal ( perpendicular) to the fiber axis, the helical axis aligned
      parallel to the applied field. On the other hand, the rotating magnetic field
      induced the uniaxial alignment of the smallest susceptibility axis, that is, chi(
      parallel) in the present case, and brought about unwinding of the helices.

PMID- 15723508
TI  - Growth induced reordering of fullerene clusters trapped in a two-dimensional
      supramolecular network.
AB  - We have investigated the growth of molecular clusters in confined geometries
      defined by a bimolecular supramolecular network. This framework provides a
      regular array of identical nanoscale traps in which further deposited molecules
      nucleate cluster growth. For the higher fullerene, C84, molecules aggregate into
      close packed assemblies with an orientation which switches when the cluster size
      increases by one molecule. This change is controlled by the interactions between
      the molecules and the confining boundaries of the network pore. We show that,
      following nucleation of small clusters, further growth requires a reconfiguration
      of previously captured molecules resulting in a transition between nanoscale
      phases with different ordering.

PMID- 15723509
TI  - Magnetic switch of permeability for polyelectrolyte microcapsules embedded with
      Co@Au nanoparticles.
AB  - We explored using a magnetic field to modulate the permeability of
      polyelectrolyte microcapsules prepared by layer-by-layer self-assembly.
      Ferromagnetic gold-coated cobalt (Co@Au) nanoparticles (3 nm diameter) were
      embedded inside the capsule walls. The final 5 mum diameter microcapsules had
      wall structures consisting of 4 bilayers of poly(sodium styrene
      sulfonate)/poly(allylamine hydrochloride) (PSS/PAH), 1 layer of Co@Au, and 5
      bilayers of PSS/PAH. External alternating magnetic fields of 100-300 Hz and 1200
      Oe were applied to rotate the embedded Co@Au nanoparticles, which subsequently
      disturbed and distorted the capsule wall and drastically increased its
      permeability to macromolecules like FITC-labeled dextran. The capsule
      permeability change was estimated by taking the capsule interior and exterior
      fluorescent intensity ratio using confocal laser scanning microscopy. Capsules
      with 1 layer of Co@Au nanoparticles and 10 polyelectrolyte bilayers are optimal
      for magnetically controlling permeability. A theoretical explanation was proposed
      for the permeability control mechanisms. "Switching on" of these microcapsules
      using a magnetic field makes this method a good candidate for controlled drug
      delivery in biomedical applications.

PMID- 15723510
TI  - Structure and diffusion characterization of SBA-15 materials.
AB  - In situ formation of the micro- and mesoporous structures of SBA-15 materials was
      investigated. It was found that the structure is significantly different from
      that for cylindrical or hexagonal pores, which suggests that the SBA-15 is more
      complex than an array of hexagonally ordered channels. Nitrogen adsorption
      isotherms at 77 K provided evidence that large (primary) mesopores are
      accompanied by a certain amount of significantly smaller pores with a broad
      distribution in the micropore/small-mesopore range within the mesoporous walls of
      main channels. It was found that the microporosity can be controlled by the time
      of heating as well as the synthesis temperature. The diffusion properties of n
      heptane as a probe molecule in four selected SBA-15 samples with different
      micropore volumes were studied by the standard zero length column technique and
      related to their structural characteristics. The results have shown that the
      diffusion process involving n-heptane at a low concentration level takes place
      inside the walls of main mesoporous channels and depends on the relative content
      of micropores. In the samples that have a relatively high content of micropores,
      n-heptane diffusivities are relatively low, their activation energies are high,
      and the process is similar to diffusion in typical microporous adsorbents, like
      zeolites. As the micropore content is decreased, diffusion becomes more and more
      controlled by secondary mesopores of the intrawall pore structure, rendering
      diffusion faster and activation energies lower.

PMID- 15723511
TI  - Size control of dendrimer-templated silica.
AB  - One of the most significant challenges facing the biomimetic synthesis of
      materials is achieving the requisite level of dimensional and spatial control.
      Typical reaction conditions for biomimetic silica synthesis allow for continued
      growth and ripening leading to the formation of larger nanospheres on the order
      of 200-600 nm in diameter. Herein, we have used polyamidoamine and
      polypropylenimine dendrimers as templates to expand the reaction conditions of
      biogenic silica production to produce a more robust synthesis leading to size
      selective precipitation of silica nanospheres. Through the use of defined
      concentrations of phosphate buffer and main group metal chloride salts, we have
      shown that the biomimetic silica growth process is controlled by cationic
      neutralization of the anionic silica nanosphere surface. Neutralization minimizes
      electrostatic repulsions, allowing for agglomerization and continued growth of
      nanospheres. By controlling these concentrations, we can selectively produce
      silica nanospheres of desired dimensions between 30 and 300 nm without adversely
      affecting the template's activity.

PMID- 15723512
TI  - Scaling of the kinetics of slow aggregation and gel formation for a fluorinated
      polymer colloid.
AB  - The aggregation and gelation kinetics in moderately concentrated (0.004 </=
      phi(0) </= 0.1) colloidal dispersions of fluorinated polymer particles has been
      studied. The aggregation was adjusted to proceed slowly enough to allow a
      convenient characterization of the kinetics through static and dynamic light
      scattering on quenched and diluted samples. A population balance model based on
      second-order aggregation rates is developed to compute the time evolution of the
      cluster mass distribution, from which we calculate the values of the average
      radii and structure factor measured by light scattering, so as to allow a direct
      comparison between measured and calculated quantities. The model suggests the
      introduction of a dimensionless time which allows the scaling of all the
      aggregation data on unique master curves defined by only two parameters: the
      exponent of the power-law aggregation kernel, lambda, and the aggregate fractal
      dimension, d(f). The predicted master curves were observed experimentally, which
      confirms the validity of the aggregation model and allows the unique
      determination of the kinetic and structural parameters of the aggregation
      process. The cluster growth behavior, although significantly slower than DLCA,
      shows power-law kinetics rather than the exponential one typical of RLCA and the
      cluster structure is characterized by an unexpectedly small fractal dimension,
      d(f) = 1.7. The occurrence of gelation has been characterized using small
      amplitude oscillatory shearing to monitor the time evolution of the elastic
      modulus. It is found that also these curves, together with the gel time value,
      scale with the stability ratio of primary particles for a given solid volume
      fraction. We further use the model to calculate the cumulative occupied volume
      fraction of the growing aggregates and quantify in this way the increasing space
      filling, which is solid volume fraction dependent. The experimentally determined
      dimensionless gel times, which are also solid volume fraction dependent, scale
      then directly with the dimensionless time to reach a certain degree of the space
      filling in the model. This finding suggests that, like the aggregation kinetics,
      the gelation kinetics is governed by a second-order rate process.

PMID- 15723513
TI  - Influence of the Al source and synthesis of ordered Al-SBA-15 hexagonal particles
      with nanostairs and terraces.
AB  - We investigated the effect of various aluminum sources on the morphology and
      microstructure of nanoporous Al-SBA-15. With aluminum tri-sec-butoxide (Al-TSB),
      very large, ordered hexagonal rods of Al-SBA-15 covered by nanostairs and
      terraces were synthesized. Such a morphology was not obtained with an inorganic
      Al source (sodium aluminate) or with organic sources seemingly similar to Al-TSB,
      such as aluminum tri-tert-butoxide, aluminum tri-n-butoxide, or aluminum
      isopropoxide. The results obtained from X-ray diffraction, scanning electron
      microscopy/transmission electron microscopy, N(2) adsorption/desorption, and high
      performance (129)Xe NMR suggest that preparing an organic Al-Si precursor by
      premixing liquid organic Al and Si sources (Al-TSB and tetraethyl orthosilicate)
      is crucial in obtaining highly ordered mesoporous Al-SBA-15 materials with a well
      defined morphology.

PMID- 15723514
TI  - Reentrant behavior of poly(N-isopropylacrylamide) brushes in water-methanol
      mixtures investigated with a quartz crystal microbalance.
AB  - The solvent composition induced reentrant behavior of poly(N-isopropylacrylamide)
      (PNIPAM) chains grafted on a SiO2 surface in water-methanol mixtures was
      investigated using a quartz crystal microbalance with dissipation monitoring (QCM
      D) at 20 degrees C. The frequency and energy dissipation responses showed that
      the grafted PNIPAM chains sharply collapse when the methanol content (x(m))
      reaches approximately 17 mol %. In the range 17-50 mol %, the grafted chains
      remain in a collapsed state. Further increase of the methanol content leads to an
      abrupt reswelling of the collapsed chains at x(m) > approximately 50 mol %. The
      sharp reentrant swelling-to-collapse-to-swelling transition was attributed to the
      water-methanol complexation instead of the preferential adsorption effect. Our
      results also suggest that the water-methanol complexation is not induced by
      hydrophobic interaction but by hydrogen bonding.

PMID- 15723515
TI  - On wet phospholipid bilayers as disclosed by the nearest-neighbor recognition
      method.

PMID- 15723516
TI  - Reward versus risk: DNA cytidine deaminases triggering immunity and disease.
AB  - The enzymatic deamination of cytosine to uracil, using the free base C, its
      nucleosides, and nucleotides as substrates, is an essential feature of nucleotide
      metabolism. However, the deamination of C and, especially, 5 methyl C on DNA is
      typically detrimental, causing mutations leading to serious human disease.
      Recently, a family of enzymes has been discovered that catalyzes the conversion
      of C to U on DNA and RNA, generating favorable mutations that are essential for
      human survival. Members of the Apobec family of nucleic acid-dependent cytidine
      deaminases include activation-induced cytidine deaminase (AID) and Apobec3G. AID
      is required for B cells to undergo somatic hypermutation (SHM) and class switch
      recombination (CSR), two processes that are needed to produce high-affinity
      antibodies of all isotypes. Apobec3G is responsible for protection against HIV
      infection. Recent advances in the biochemical and structural analyses of nucleic
      acid cytidine deaminases will be discussed in relation to their programmed roles
      in ensuring antibody diversification and in imposing innate resistance against
      retroviral infection. The serious negative consequences of expressing Apobec
      deaminases in the wrong place at the wrong time to catalyze aberrant deamination
      in "at risk" sequences will be discussed in terms of causing genomic instability
      and disease.

PMID- 15723517
TI  - Interactions of the HIV-1 Tat and RAP74 proteins with the RNA polymerase II CTD
      phosphatase FCP1.
AB  - FCP1, a phosphatase specific for the carboxyl-terminal domain of the largest
      subunit of RNA polymerase II, is regulated by the HIV-1 Tat protein, CK2, TFIIB,
      and the large subunit of TFIIF (RAP74). We have characterized the interactions of
      Tat and RAP74 with the BRCT-containing central domain of FCP1 (FCP1(562)(
      )(738)). We demonstrated that FCP1 is required for Tat-mediated transactivation
      in vitro and that amino acids 562-685 of FCP1 are necessary for Tat interaction
      in yeast two-hybrid studies. From sequence alignments, we identified a conserved
      acidic/hydrophobic region in FCP1 adjacent to its highly conserved BRCT domain.
      In vitro binding studies with purified proteins indicate that HIV-1 Tat interacts
      with both the acidic/hydrophobic region and the BRCT domain of FCP1, whereas
      RAP74(436)(-)(517) interacts solely with a portion of the acidic/hydrophobic
      region containing a conserved LXXLL-like motif. HIV-1 Tat inhibits the binding of
      RAP74(436)(-)(517) to FCP1. In a companion paper (K. Abbott et al. (2005)
      Enhanced Binding of RNAPII CTD Phosphatase FCP1 to RAP74 Following CK2
      Phosphorylation, Biochemistry 44, 2732-2745, we identified a novel CK2 site
      adjacent to this conserved LXXLL-like motif. Phosphorylation of FCP1(562)(-)(619)
      by CK2 at this site increases binding to RAP74(436)(-)(517), but this
      phosphorylation is inhibited by Tat. Our results provide insights into the
      mechanisms by which Tat inhibits the FCP1 CTD phosphatase activity and by which
      FCP1 mediates transcriptional activation by Tat. In addition to increasing our
      understanding of the role of HIV-1 Tat in transcriptional regulation, this study
      defines a clear role for regions adjacent to the BRCT domain in promoting
      important protein-protein interactions.

PMID- 15723518
TI  - Enhanced binding of RNAP II CTD phosphatase FCP1 to RAP74 following CK2
      phosphorylation.
AB  - FCP1 (TFIIF-associated CTD phosphatase) is the first identified CTD-specific
      phosphatase required to recycle RNA polymerase II (RNAP II). FCP1 activity has
      been shown to be regulated by the general transcription factors TFIIF (RAP74) and
      TFIIB, protein kinase CK2 (CK2), and the HIV-1 transcriptional activator Tat.
      Phosphorylation of FCP1 by CK2 stimulates FCP1 phosphatase activity and enhances
      binding of RAP74 to FCP1. We have examined consensus CK2 phosphorylation sites
      (acidic residue n + 3 to serine or threonine residue) located immediately
      adjacent to both RAP74-binding sites of FCP1. We demonstrate that both of these
      consensus CK2 sites can be phosphorylated in vitro and that phosphorylation at
      either CK2 site results in enhanced binding of RAP74 to FCP1. The CK2 site
      adjacent to the RAP74-binding site in the central domain of FCP1 is
      phosphorylated at a single threonine site (T584). The CK2 site adjacent to the
      RAP74-binding site in the carboxyl-terminal domain can be phosphorylated at three
      successive serine residues (S942-S944), with phosphorylations at S942 and S944
      both contributing to enhanced binding to RAP74. With the use of tandem Fourier
      transform-ion cyclotron resonance mass spectrometry (FT-ICR), we demonstrate that
      the phosphorylation of S942-S944 occurs in a semiordered fashion with the initial
      phosphorylation occurring at either S942 or S944 followed by a second
      phosphorylation to yield the S942/S944 diphosphorylated species. Using nuclear
      magnetic resonance (NMR) spectroscopy, we identify and map chemical shift changes
      onto the solution structure of the carboxyl-terminal domain of RAP74 (RAP74(436)(
      )(517)) on complexation of RAP74(436)(-)(517) with phosphorylated FCP1 peptides.
      These results provide new functional and structural information on the role of
      phosphorylation in the recognition of acidic-rich activation domains involved in
      transcriptional regulation, and bring insights into how CK2 and TFIIF regulate
      FCP1 function.

PMID- 15723519
TI  - Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a
      target for rational drug design: binding mode of a new class of purinetrione
      inhibitors.
AB  - The enzymes involved in the biosynthesis of riboflavin represent attractive
      targets for the development of drugs against bacterial pathogens, because the
      inhibitors of these enzymes are not likely to interfere with enzymes of the
      mammalian metabolism. Lumazine synthase catalyzes the penultimate step in the
      riboflavin biosynthesis pathway. A number of substituted purinetrione compounds
      represent a new class of highly specific inhibitors of lumazine synthase from
      Mycobacterium tuberculosis. To develop potent antibiotics for the treatment of
      tuberculosis, we have determined the structure of lumazine synthase from M.
      tuberculosis in complex with two purinetrione inhibitors and have studied binding
      via isothermal titration calorimetry. The structures were determined by molecular
      replacement using lumazine synthase from Saccharomyces cerevisiae as a search
      model and refined at 2 and 2.3 A resolution. The R-factors were 14.7 and 17.4%,
      respectively, and the R(free) values were 19.3 and 26.3%, respectively. The
      enzyme was found to be a pentamer consisting of five subunits related by 5-fold
      local symmetry. The comparison of the active site architecture with the active
      site of previously determined lumazine synthase structures reveals a largely
      conserved topology with the exception of residues Gln141 and Glu136, which
      participate in different charge-charge interactions in the core space of the
      active site. The impact of structural changes in the active site on the altered
      binding and catalytic properties of the enzyme is discussed. Isothermal titration
      calorimetry measurements indicate highly specific binding of the purinetrione
      inhibitors to the M. tuberculosis enzyme with dissociation constants in
      micromolar range.

PMID- 15723520
TI  - A three-dimensional molecular model of lipid-free apolipoprotein A-I determined
      by cross-linking/mass spectrometry and sequence threading.
AB  - Apolipoprotein (apo) A-I, a 243-residue, 28.1-kDa protein is a major mediator of
      the reverse cholesterol transport (RCT) pathway, a process that may reduce the
      risk of cardiovascular disease in humans. In plasma, a small fraction of lipid
      free or lipid-poor apoA-I is likely a key player in the first step of RCT.
      Therefore, a basic understanding of the structural details of lipid-free apoA-I
      will be useful for elucidating the molecular details of the pathway. To address
      this issue, we applied the combined approach of cross-linking chemistry and high
      resolution mass spectrometry (MS) to obtain distance constraints within the
      protein structure. The 21 lysine residues within apoA-I were treated with homo
      bifunctional chemical cross-linkers capable of covalently bridging two lysine
      residues residing within a defined spacer arm length. After trypsin digestion of
      the sample, individual peptide masses were identified by MS just after liquid
      chromatographic separation. With respect to the linear amino acid sequence, we
      identified 5 short-range and 12 long-range cross-links within the monomeric form
      of lipid-free apoA-I. Using the cross-linker spacer arm length as a constraint
      for identified Lys pairs, a molecular model was built for the lipid-free apoA-I
      monomer based on homology with proteins of similar sequence and known three
      dimensional structures. The result is the first detailed model of lipid-free apoA
      I. It depicts a helical bundle structure in which the N- and C-termini are in
      close proximity. Furthermore, our data suggest that the self-association of lipid
      free apoA-I occurs via C- and N-termini of the protein based on the locations of
      six cross-links that are unique to the cross-linked dimeric form of apoA-I.

PMID- 15723521
TI  - Characterization of the formation of the pyrrole moiety during clorobiocin and
      coumermycin A1 biosynthesis.
AB  - The aminocoumarin antibiotics clorobiocin and coumermycin A(1) target the B
      subunit of DNA gyrase by presentation of the 5-methyl-pyrrolyl-2-carboxy ester
      moiety in the ATP-binding site of the enzyme. The pyrrolyl pharmacophore is
      derived by a four electron oxidation of a prolyl unit while tethered in
      phosphopantetheinyl thioester linkage to a peptidyl carrier protein (PCP)
      subunit. l-Proline is selected and activated as l-prolyl-AMP by adenylation
      domain enzymes (CloN4 and CouN4) and then installed as the thioester on the holo
      form of the PCP proteins CloN5 and CouN5. Enzymatic oxidation of the prolyl-S-PCP
      by the flavoprotein dehydrogenase CloN3 can be followed by rapid quench and
      subsequent electrospray ionization-Fourier transform mass spectrometry analysis
      of the acyl-S-protein substrate/product mixture to establish that a two-electron
      oxidized pyrrolinyl-S-enzyme transiently accumulates on the way to the four
      electron oxidized, heteroaromatic pyrrolyl-2-carboxy-S-PCP acyl enzyme product.

PMID- 15723522
TI  - Probing the cruzain S2 recognition subsite: a kinetic and binding energy
      calculation study.
AB  - Cysteine proteases are relevant to several aspects of the parasite life cycle and
      the parasite-host relationship. Moreover, they appear as promising targets for
      antiparasite chemotherapy. Here, a quantitative investigation on the catalytic
      properties of cruzain, the papain-like cysteine protease from epimastigotes of
      Trypanosoma cruzi, is reported. The results indicate that kinetics for the
      cruzain catalyzed hydrolysis of N-alpha-benzyloxycarbonyl-l-arginyl-l-alanine-(7
      amino-4-methylcoumarin), N-alpha-benzyloxycarbonyl-l-phenylalanyl-l-alanine-(7
      amino-4-methylcoumarin), and N-alpha-benzyloxycarbonyl-l-tyrosyl-l-alanine-(7
      amino-4-methylcoumarin) can be consistently fitted to the minimum three-step
      mechanism of cysteine proteases involving the acyl.enzyme intermediate E.P; the
      deacylation step is rate-limiting in enzyme catalysis. Remarkably, these
      substrates show identical catalytic parameters. This reflects the ability of the
      cruzain Glu205 residue, located at the bottom of the S(2) subsite, to neutralize
      the substrate/inhibitor polar P(2) residues (e.g., Arg or Tyr) and to be solvent
      exposed when substrate/inhibitor nonpolar P(2) residues (e.g., Phe) fit the S(2)
      subsite. More complex catalytic mechanisms are also discussed. Binding free
      energy calculation provides a quantitative framework for the interpretation of
      these results; in particular, direct evidence for the compensatory effect between
      Coulomb interaction(s) and solvation effect(s) is reported. These results appear
      of general significance for a deeper understanding of (macro)molecular
      recognition and for the rational design of novel inhibitors of parasitic cysteine
      proteases.

PMID- 15723523
TI  - Solution structure of human SUMO-3 C47S and its binding surface for Ubc9.
AB  - Small ubiquitin-related modifier SUMO-3 is a member of a growing family of
      ubiquitin-like proteins (Ubls). So far, four isoforms of SUMO have been
      identified in humans. It is generally known that SUMO modification regulates
      protein localization and activity. Previous structure and function studies have
      been mainly focused on SUMO-1. The sequence of SUMO-3 is 46% identical with that
      of SUMO-1; nevertheless, functional heterogeneity has been found between the two
      homologues. Here we report the solution structure of SUMO-3 C47S (residues 14-92)
      featuring the beta-beta-alpha-beta-beta-alpha-beta ubiquitin fold. Structural
      comparison shows that SUMO-3 C47S resembles ubiquitin more than SUMO-1. On the
      helix-sheet interface, a strong hydrophobic interaction contributes to formation
      of the globular and compact fold. A Gly-Gly motif at the C-terminal tail,
      extending away from the core structure, is accessible to enzymes and substrates.
      In vivo, SUMO modification proceeds via a multistep pathway, and Ubc9 plays an
      indispensable role as the SUMO conjugating enzyme (E2) in this process. To
      develop a better understanding of SUMO-3 conjugation, the Ubc9 binding surface on
      SUMO-3 C47S has been detected by chemical shift perturbation using NMR
      spectroscopy. The binding site mainly resides on the hydrophilic side of the beta
      sheet. Negatively charged and hydrophobic residues of this region are highly or
      moderately conserved among SUMO family members. Notably, the negatively charged
      surface of SUMO-3 C47S is highly complementary in its electrostatic potentials
      and hydrophobicity to the positively charged surface of Ubc9. This work indicates
      dissimilarities between SUMO-3 and SUMO-1 in tertiary structure and provides
      insight into the specific interactions of SUMO-3 with its modifying enzyme.

PMID- 15723525
TI  - Phospholipase A2 hydrolysis of supported phospholipid bilayers: a neutron
      reflectivity and ellipsometry study.
AB  - We have investigated the phospholipase A(2) catalyzed hydrolysis of supported
      phospholipid bilayers using neutron reflection and ellipsometry. At the
      hydrophilic silica-water interface, hydrolysis of phosphatidylcholine bilayers by
      phospholipase A(2) from Naja mossambica mossambica venom is accompanied by
      destruction of the bilayer at an initial rate, which is comparable for DOPC and
      DPPC but is doubled for POPC. The extent of bilayer destruction at 25 degrees C
      decreases from DOPC to POPC and is dramatically reduced for DPPC. Neutron
      reflectivity measurements indicate that the enzyme penetrates into the bilayers
      in increasing order for DOPC, POPC, and DPPC, while the amount of enzyme adsorbed
      at the interface is smallest for DPPC and exhibits a maximum for POPC.
      Penetration into the hydrophobic chain region in the bilayer is further supported
      by the fact that the enzyme adsorbs strongly and irreversibly to a hydrophobic
      monolayer of octadecyltrichlorosilane. These results are rationalized in terms of
      the properties of the reaction products and the effect of their accumulation in
      the membrane on the kinetics of enzyme catalysis.

PMID- 15723524
TI  - Association of sindbis virus capsid protein with phospholipid membranes and the
      E2 glycoprotein: implications for alphavirus assembly.
AB  - A late stage in assembly of alphaviruses within infected cells is thought to be
      directed by interactions between the nucleocapsid and the cytoplasmic domain of
      the E2 protein, a component of the viral E1/E2 glycoprotein complex that is
      embedded in the plasma membrane. Recognition between the nucleocapsid protein and
      the E2 protein was explored in solution using NMR spectroscopy, as well as in
      binding assays using a model phospholipid membrane system that incorporated a
      variety of Sindbis virus E2 cytoplasmic domain (cdE2) and capsid protein
      constructs. In these binding assays, synthetic cdE2 peptides were reconstituted
      into phospholipid vesicles to simulate the presentation of cdE2 on the inner
      leaflet of the plasma membrane. Results from these binding assays showed a direct
      interaction between a peptide containing the C-terminal 16 amino acids of the
      cdE2 sequence and a Sindbis virus capsid protein construct containing amino acids
      19-264. Additional experiments that probed the sequence specificity of this cdE2
      capsid interaction are also described. Further binding assays demonstrated an
      interaction between the 19-264 capsid protein and artificial vesicles containing
      neutral or negatively charged phospholipids, while capsid protein constructs with
      N-terminal truncations displayed either little or no affinity for such vesicles.
      The membrane-binding property of the capsid protein suggests that the membrane
      may play an active role in alphavirus assembly. The results are consistent with
      an assembly process involving an initial membrane association, whereby an
      association with E2 glycoprotein further enhances capsid binding to facilitate
      membrane envelopment of the nucleocapsid for budding. Collectively, these
      experiments elucidate certain requirements for the binding of Sindbis virus
      capsid protein to the cytoplasmic domain of the E2 glycoprotein, a critical event
      in the alphavirus maturation pathway.

PMID- 15723526
TI  - Solution structure, stability, and flexibility of Sso10a: a hyperthermophile
      coiled-coil DNA-binding protein.
AB  - Sso10a is one of a number of DNA-binding proteins from the hyperthermophile
      Sulfolobus solfataricus that has been associated with DNA packaging and chromatin
      regulation. Sequence analysis indicates that it is a member of a conserved group
      of archaeal transcription regulators (COG3432). We have determined the solution
      structure of Sso10a and show that it is a homodimer of winged-helix DNA-binding
      domains. The dimer interface consists of an extended antiparallel coiled coil,
      with the globular DNA-binding domains positioned at opposite ends of a solvent
      exposed coiled-coil rod. NMR structure refinement of the elongated structure
      benefited not only from the inclusion of residual dipolar couplings from
      partially aligned samples but also the influence of anisotropic rotational
      diffusion on heteronuclear relaxation. An analysis of backbone mobility using
      (15)N relaxation rates indicated that the overall tertiary and quaternary
      structure is largely inflexible on the nanosecond to picosecond time scale. Amide
      hydrogen exchange data demonstrated that the most stable region of the protein
      extends from the core of the winged helices into the coiled coil. The positions
      of the globular heads relative to the coiled coil in solution deviate only
      slightly from that observed in a crystal structure. The most significant
      difference between the solution and crystal structures occurs in the putative DNA
      binding helix-turn-helix (HTH) motif. This is the region of lowest stability in
      solution and a point of protein-protein contact in the crystal. Alternative
      conformations of the HTH motif may permit adjustment of the structure for optimal
      DNA binding.

PMID- 15723527
TI  - The conserved core domains of annexins A1, A2, A5, and B12 can be divided into
      two groups with different Ca2+-dependent membrane-binding properties.
AB  - The hallmark of the annexin super family of proteins is Ca(2+)-dependent binding
      to phospholipid bilayers, a property that resides in the conserved core domain of
      these proteins. Despite the structural similarity between the core domains,
      studies reported herein showed that annexins A1, A2, A5, and B12 could be divided
      into two groups with distinctively different Ca(2+)-dependent membrane-binding
      properties. The division correlates with the ability of the annexins to form
      Ca(2+)-dependent membrane-bound trimers. Site-directed spin-labeling and Forster
      resonance energy transfer experimental approaches confirmed the well-known
      ability of annexins A5 and B12 to form trimers, but neither method detected self
      association of annexin A1 or A2 on bilayers. Studies of chimeras in which the N
      terminal and core domains of annexins A2 and A5 were swapped showed that trimer
      formation was mediated by the core domain. The trimer-forming annexin A5 and B12
      group had the following Ca(2+)-dependent membrane-binding properties: (1) high
      Ca(2+) stoichiometry for membrane binding ( approximately 12 mol of Ca(2+)/mol of
      protein); (2) binding to membranes was very exothermic (> -60 kcal/ mol of
      protein); and (3) binding to bilayers that were in the liquid-crystal phase but
      not to bilayers in the gel phase. In contrast, the nontrimer-forming annexin A1
      and A2 group had the following Ca(2+)-dependent membrane-binding properties: (1)
      lower Ca(2+) stoichiometry for membrane binding (<or=4 mol of Ca(2+)/mol of
      protein); (2) binding to membranes was relatively less exothermic (< -33 kcal/
      mol of protein); and (3) binding to bilayers that were in either the liquid
      crystal phase or gel phase. The biological implications of this subdivision are
      discussed.

PMID- 15723528
TI  - Solution structure of an RNA internal loop with three consecutive sheared GA
      pairs.
AB  - Internal loops in RNA are important for folding and function. Many folding motifs
      are internal loops containing GA base pairs, which are usually thermodynamically
      stabilizing, i.e., contribute favorable free energy to folding. Understanding the
      sequence dependence of folding stability and structure in terms of molecular
      interactions, such as hydrogen bonding and base stacking, will provide a
      foundation for predicting stability and structure. Here, we report the NMR
      structure of the oligonucleotide duplex, 5'GGUGGAGGCU3'/3'PCCGAAGCCG5' (P =
      purine), containing an unusually stable and relatively abundant internal loop,
      5'GGA3'/3'AAG5'. This loop contains three consecutive sheared GA pairs (trans
      Hoogsteen/Sugar edge AG) with separate stacks of three G's and three A's in a
      row. The thermodynamic consequences of various nucleotide substitutions are also
      reported. Significant destabilization of approximately 2 kcal/mol at 37 degrees C
      is found for substitution of the middle GA with AA to form 5'GAA3'/3'AAG5'. This
      destabilization correlates with a unique base stacking and hydrogen-bonding
      network within the 5'GGA3'/3'AAG5' loop. Interestingly, the motifs, 5'UG3'/3'GA5'
      and 5'UG3'/3'AA5', have stability similar to 5'CG3'/3'GA5' even though UG and UA
      pairs are usually less stable than CG pairs. Consecutive sheared GA pairs in the
      5'GGA3'/3'AAG5' loop are preorganized for potential tertiary interactions and
      ligand binding.

PMID- 15723529
TI  - Binding of endostatin to phosphatidylserine-containing membranes and formation of
      amyloid-like fibers.
AB  - Endostatin, the 20-kDa C-terminal NC1 domain of collagen XVIII, is an endogenous
      inhibitor of tumor angiogenesis and tumor growth. A major problem in reconciling
      the many reported in vitro effects of endostatin is the lack of a high-affinity
      receptor, and a search for the latter continues. In accordance with the above,
      the molecular mechanisms of action of endostatin remain elusive. We show here
      that endostatin binds to membranes containing acidic phospholipids,
      phosphatidylserine (PS) or phosphatidylglycerol (PG). More specifically, a red
      shift in the fluorescence emission of Trp of endostatin in the presence of
      liposomes containing these anionic lipids was evident, revealing the average
      environment of Trps to become less hydrophobic. This shift was not observed for
      phosphatidylcholine (PC) liposomes, demonstrating the acidic lipid to be
      required. Quenching by endostatin of the fluorescence of a pyrene-labeled
      phospholipid analogue in PS containing membranes was seen, while there was no
      effect for PC liposomes. Resonance energy transfer from the Trp residues of
      endostatin to a dansyl-labeled phospholipid further confirmed the association of
      endostatin with PS-containing membranes, whereas there was no binding to PC
      liposomes. Intriguingly, the association of endostatin with PS-containing
      liposomes triggered the formation of fibers, with Congo red staining producing
      green birefringence characteristic for amyloid. Lipid was incorporated into these
      fibers, as shown by staining when a trace amount (X = 0.02) of fluorescent
      phospholipid analogues was present in the liposomes. No fiber formation was seen
      when endostatin was added to liposomes composed of PC only. Because PS has been
      reported to be exposed in the outer surface of the plasma membrane of cancer
      cells and vascular endothelial cells, our results suggest that this lipid could
      represent a target for endostatin in the cancer cell surface and tumors, thus
      suggesting a novel mechanism of its action. More specifically, analogous to a
      number of other cytotoxic proteins interacting with negatively charged lipids, PS
      triggered fiber formation by endostatin on the surface of cancer cells would
      impair the permeability barrier function of the plasma membrane, resulting in
      cell death.

PMID- 15723530
TI  - Structural analysis of sterol distributions in the plasma membrane of living
      cells.
AB  - Although plasma membrane (PM) cholesterol-rich and -poor domains have been
      isolated by subcellular fractionation, the real-time arrangement of cholesterol
      in such domains in living cells is still unclear. Therefore, dehydroergosterol
      (DHE), a naturally occurring fluorescent sterol, was incorporated into cultured L
      cell fibroblasts. Two PM markers, the enhanced cyan fluorescent protein (ECFP
      Mem) and 3'-dioctadecyloxacarbocyanine perchlorate [DiOC(18)(3)], were used to
      distinguish DHE localized at the PM of living cells. Spatial enrichment of DHE in
      the PM of living cells was visualized in real time by multiphoton laser scanning
      microscopy (MPLSM). Quantitative models and image-processing techniques were
      developed for statistical analysis of the distribution of DHE within the PM. The
      PM was resolved from the cytoplasm in a two-step process, and a smooth trajectory
      reference of the PM was refined by statistical regression and moments-based
      techniques. Thus, DHE intensities over the PM were measured following the major
      DHE intensity distributions. Spatial distributions of DHE within the PM were
      examined by a statistical inference technique, complete spatial randomness (CSR).
      For PM regions densely populated with DHE, the distributions of DHE exhibited
      statistical arrangements that were not spatial random (i.e., homogeneous Poisson
      process) or regular but, instead, exhibited strong cluster patterns. In effect,
      real-time MPLSM imaging data for the first time demonstrated that sterol
      enrichment occurred in clustered regions in the PM, consistent with the existence
      of cholesterol-rich domains in the plasma membrane of living cells.

PMID- 15723531
TI  - Toward defining the human parotid gland salivary proteome and peptidome:
      identification and characterization using 2D SDS-PAGE, ultrafiltration, HPLC, and
      mass spectrometry.
AB  - Saliva plays many biological roles, from lubrication and digestion to regulating
      bacterial and leukocyte adhesion. To understand the functions of individual
      components and families of molecules, it is important to identify as many
      salivary proteins as possible. Toward this goal, we used a proteomic approach as
      the first step in a global analysis of this important body fluid. We collected
      parotid saliva as the ductal secretion from three human donors and separated the
      protein components by two-dimensional SDS-polyacrylamide gel electrophoresis (2D
      SDS-PAGE). Proteins in gel spots were identified by peptide mass fingerprinting,
      and the results were confirmed by tandem mass spectrometry of selected peptides.
      Complementing this approach we used ultrafiltration to prepare a low-molecular
      weight fraction of parotid saliva, which was analyzed directly or after reversed
      phase high-performance liquid chromatography separation by using mass
      spectrometric approaches. MS analyses of 2D SDS-PAGE spots revealed known
      components of saliva, including cystatins, histatins, lysozyme, and isoforms
      and/or fragments of alpha-amylase, albumin, and proline-rich proteins. We also
      discovered novel proteins, such as several isoforms of Zn-alpha-2-glycoprotein
      and secretory actin-binding protein. MS analyses of the ultrafiltrate showed that
      the low-molecular-weight fraction of parotid saliva was peptide-rich, with novel
      fragments of proline-rich proteins and histatins in abundance. Experiments using
      Candida albicans as the test organism showed that at least one of the novel
      peptides had antifungal activity. Our results show that saliva is a rich source
      of proteins and peptides that are potential diagnostic and therapeutic targets.

PMID- 15723532
TI  - Role of hydrogen bond networks and dynamics in positive and negative cooperative
      stabilization of a protein.
AB  - Cooperativity mediated through hydrogen bond networks in yeast iso-1-cytochrome c
      was studied using a thermodynamic triple mutant cycle. Three known stabilizing
      mutations, Asn 26 to His, Asn 52 to Ile, and Tyr 67 to Phe, were used to
      construct the triple mutant cycle. The side chain of His 26, a wild-type residue,
      forms two hydrogen bonds that bridge two substructures of the wild-type protein,
      and Tyr 67 and Asn 52 are part of an extensive buried hydrogen bond network. The
      stabilities of all variants in the triple mutant cycle were determined by
      guanidine hydrochloride denaturation methods and used to determine the pairwise,
      Delta(2)G(int), and triple interaction energies. His 26 and Ile 52 interact
      cooperatively (Delta(2)G(int) is 1-2 kcal/mol), whereas the two other pairs of
      mutations interact anticooperatively (Delta(2)G(int) is -0.5 to -1.5 kcal/mol).
      Previously reported structural data for iso-1-cytochrome c variants containing
      these mutations show that changes in the strength of the His 26 to Glu 44
      hydrogen bond, apparently caused by changes in main chain dynamics, provide a
      mechanism for the long distance (His 26 to Phe 67 and His 26 to Ile 52)
      propagation of pairwise interaction energies. Opposing changes in the strength of
      the His 26 to Glu 44 hydrogen bond caused by the N52I and Y67F mutations generate
      a negative triple interaction energy (-0.9 +/-0.7 kcal/mol) that combined with
      cancellation of cooperative and anticooperative pairwise interactions produce
      apparent additivity for the stabilizing effects of the single mutations in the
      triple mutant variant.

PMID- 15723533
TI  - Structural changes of the complex between pharaonis phoborhodopsin and its
      cognate transducer upon formation of the M photointermediate.
AB  - pharaonis phoborhodopsin (ppR, also called pharaonis sensory rhodopsin II, psRII)
      is a receptor for negative phototaxis in Natronobacterium pharaonis. It forms a
      2:2 complex with its transducer protein, pHtrII, in membranes, and the
      association is weakened by 2 orders of magnitude in the M intermediate. Such
      change is believed to correspond to the transfer of the light signal to pHtrII.
      In this paper, we applied Fourier transform infrared (FTIR) spectroscopy to the
      active M intermediate in the absence and presence of pHtrII. The obtained
      difference FTIR spectra were surprisingly similar, notwithstanding the presence
      of pHtrII. This result strongly suggests that the transducer activation in the
      ppR-pHtrII system does not induce secondary structure alterations of the pHtrII
      itself. On the other hand, we found that the hydrogen bond of the OH group of
      Thr204 is altered in the primary K intermediate, but restored in the M
      intermediate. The hydrogen bond of Asn74 in pHtrII is strengthened in M,
      presumably because of the change in interaction with Tyr199 of ppR. These facts
      provided a light signaling pathway from Lys205 (retinal) of the receptor to Asn74
      of the transducer through Thr204 and Tyr199. Transducer activation is likely to
      involve a relaxation of Thr204 in the receptor and hydrogen bonding alteration of
      Asn74 in the transducer, during which the helices of the transducer perform rigid
      body motion without changing their secondary structures.

PMID- 15723534
TI  - The Mcm467 complex of Saccharomyces cerevisiae is preferentially activated by
      autonomously replicating DNA sequences.
AB  - We have analyzed the role of single-stranded DNA (ssDNA) in the modulation of the
      ATPase activity of Mcm467 helicase of the yeast Saccharomyces cerevisiae. The
      ATPase activity of the Mcm467 complex is modulated in a sequence-specific manner
      and that the ssDNA sequences derived from the origin of DNA replication of S.
      cerevisiae autonomously replicating sequence 1 (ARS1) are the most effective
      stimulators. Synthetic oligonucleotides, such as oligo(dA) and oligo(dT), also
      stimulated the ATPase activity of the Mcm467 complex, where oligo(dT) was more
      effective than oligo(dA). However, the preference of a thymidine stretch appeared
      unimportant, because with yeast ARS1 derived sequences, the A-rich strand was as
      effective in stimulating the ATPase activity, as was the T-rich strand. Both of
      these strands were more effective stimulators than either oligo(dA)( )()or
      oligo(dT). The DNA helicase activity of Mcm467 complex is also significantly
      stimulated by the ARS1-derived sequences. These results indicate that the ssDNA
      sequences containing A and B1 motifs of ARS1, activate the Mcm467 complex and
      stimulate its ATPase and DNA helicase activities. Our results also indicate that
      the yeast replication protein A stimulated the ATPase activity of the Mcm467
      complex.

PMID- 15723535
TI  - Hexitol nucleic acid-containing aptamers are efficient ligands of HIV-1 TAR RNA.
AB  - The transactivation responsive element (TAR) plays a crucial role in the
      transcription of the HIV-1 genome upon specific binding of the viral protein Tat
      and cellular proteins. We have previously identified a RNA hairpin aptamer
      forming a stable and specific kissing complex with TAR RNA (Duconge, F., and
      Toulme, J. J. (1999) RNA 5, 1605-1614). We chemically modified this aptamer with
      hexitol nucleic acid (HNA) residues. We demonstrate that a fully HNA-modified
      aptamer is a poor ligand but, in contrast, mixmers containing both HNA and
      unmodified RNA nucleotides display interesting properties. Two HNA-RNA mixmers
      bind to TAR with an equilibrium dissociation constant in the low-nanomolar range
      and show a reduced nuclease sensitivity. In addition, they show a moderate
      dependence on magnesium ions for binding to TAR. These HNA-RNA mixmers are able
      to inhibit transactivation of transcription in an in vitro assay.

PMID- 15723536
TI  - Identification of a disulfide switch in BsSco, a member of the Sco family of
      cytochrome c oxidase assembly proteins.
AB  - BsSco is a membrane-associated protein from Bacillus subtilis characterized by
      the sequence CXXXCP, which is conserved in yeast and human mitochondrial Sco
      proteins, and their bacterial homologues. BsSco is involved in the assembly of
      the Cu(A) center in cytochrome c oxidase and may play a role in the transfer of
      copper to this site. We have characterized the soluble domain of BsSco by
      biochemical, spectroscopic, and structural approaches. Soluble BsSco is monomeric
      in solution, and the two conserved cysteines are involved in an intramolecular
      cystine bridge. The cystine bridge is easily reduced, and circular dichroism
      spectroscopy shows no large-scale changes in BsSco's secondary structure upon
      reduction. The crystal structure of soluble BsSco, determined at 1.7 A
      resolution, reveals typical elements of a thioredoxin fold. The CXXXCP motif, in
      which Cys45 and Cys49 are conserved, is located in a turn structure on the
      surface of the protein. In various native and His135Ala mutant structures, both
      disulfide-bonded and non-disulfide-bonded forms of CXXXCP are observed. However,
      despite extensive attempts, copper has not been found near or beyond the CXXXCP
      motif, a presumptive copper-binding site. Another potential copper binding
      residue, His135, is located in a highly flexible loop parallel to the CXXXCP loop
      but is more than 10 A from Cys45 and Cys49. If these three residues are to
      coordinate copper, a conformational change is necessary. The structural
      identification of a disulfide switch demonstrates that BsSco has the capability
      to fill a redox role in Cu(A) assembly.

PMID- 15723537
TI  - Identification of residues in human neuroglobin crucial for Guanine nucleotide
      dissociation inhibitor activity.
AB  - Neuroglobin (Ngb) is a recently discovered vertebrate heme protein that is
      expressed in the brain and can reversibly bind oxygen. We previously demonstrated
      that ferric human Ngb binds to the alpha-subunits of heterotrimeric G proteins
      (Galpha) and acts as a guanine nucleotide dissociation inhibitor (GDI) for
      Galpha. Here we have investigated the interaction between Ngb and Galpha in more
      detail. We report that zebrafish Ngb, which shares about 50% amino acid sequence
      identity with human Ngb, does not have a GDI activity for Galpha. By carrying out
      exon swapping between zebrafish and human Ngb and site-directed mutagenesis, we
      have identified several residues that are crucial for the GDI activity of human
      Ngb.

PMID- 15723538
TI  - Crystal structures of 2-methylisocitrate lyase in complex with product and with
      isocitrate inhibitor provide insight into lyase substrate specificity, catalysis
      and evolution.
AB  - Two crystal structures of the C123S mutant of 2-methylisocitrate lyase have been
      determined, one with the bound reaction products, Mg(2+)-pyruvate and succinate,
      and the second with a bound Mg(2+)-(2R,3S)-isocitrate inhibitor. Comparison with
      the structure of the wild-type enzyme in the unbound state reveals that the
      enzyme undergoes a conformational transition that sequesters the ligand from
      solvent, as previously observed for two other enzyme superfamily members,
      isocitrate lyase and phosphoenolpyruvate mutase. The binding modes reveal the
      determinants of substrate specificity and stereoselectivity, and the stringent
      specificity is verified in solution using various potential substrates. A model
      of bound 2-methylisocitrate has been developed based on the experimentally
      determined structures. We propose a catalytic mechanism involving an alpha
      carboxy-carbanion intermediate/transition state, which is consistent with
      previous stereochemical experiments showing inversion of configuration at the
      C(3) of 2-methylisocitrate. Structure-based sequence analysis and phylogenic tree
      construction reveal determinants of substrate specificity, highlight nodes of
      divergence of families, and predict enzyme families with new functions.

PMID- 15723540
TI  - Chemical mechanism and substrate specificity of RhlI, an acylhomoserine lactone
      synthase from Pseudomonas aeruginosa.
AB  - The enzyme RhlI catalyzes the formation of N-butyrylhomoserine lactone from S
      adenosylmethionine and N-butyrylacyl carrier protein. N-Butyrylhomoserine lactone
      serves as a quorum-sensing signal molecule in Pseudomonas aeruginosa, and is
      implicated in the regulation of many processes involved in bacterial virulence
      and infectivity. The P. aeruginosa genome contains three genes encoding acyl
      carrier proteins. We have cloned all three genes, expressed the acyl carrier
      proteins, and characterized each as a substrate for RhlI. A continuous,
      spectrophotometric assay was developed to facilitate kinetic and mechanistic
      studies of RhlI. Acp1, which has not been characterized previously, was a good
      substrate for RhlI, with a K(m) of 7 microM; the reaction proceeded with a k(cat)
      value of 0.35 s(-1). AcpP, which supports fatty acid biosynthesis, was also a
      good substrate in the RhlI reaction, where k(cat) was 0.46 s(-1), and the K(m)
      for AcpP was 6 microM. The third acyl carrier protein, Acp3, was a poor substrate
      for RhlI, with a K(m) of 280 microM; k(cat) was 0.03 s(-1). Taken together with
      microarray data from the literature which show that expression of the gene
      encoding Acp1 is under the control of the quorum-sensing system, our data suggest
      that Acp1 is likely to be the substrate for RhlI in vivo. Isotope labeling
      studies were conducted to investigate the chemical mechanism of the RhlI
      catalyzed lactonization reaction. Solvent deuterons were not incorporated into
      product, which implicates a direct attack mechanism in which the carboxylate
      oxygen of the presumptive N-butyryl-SAM intermediate attacks the methylene carbon
      adjacent to the sulfonium ion. Alternative mechanisms, in which N
      butyrylvinylglycine is formed via elimination of methylthioadenosine, were ruled
      out on the basis of the observation that RhlI failed to convert authentic N
      butyrylvinylglycine to N-butyryl-L-homoserine lactone.

PMID- 15723539
TI  - p-Cresol methylhydroxylase: alteration of the structure of the flavoprotein
      subunit upon its binding to the cytochrome subunit.
AB  - The structures of two forms of a recombinant flavoprotein have been determined at
      high resolution and compared. These proteins are (1) the flavocytochrome c p
      cresol methylhydroxylase (rPCMH, 1.85 A resolution) and (2) the cytochrome-free
      flavoprotein subunit of rPCMH (PchF, 1.30 A resolution). A significant
      conformational difference is observed in a protein segment that is in contact
      with the re face of the isoalloxazine ring of FAD when the structure of PchF is
      compared to the subunit in the intact flavocytochrome. This structural change is
      important for optimum catalytic function of the flavoprotein, which has been
      shown to be dependent on the presence of the cytochrome subunit. This change
      results in different protein-flavin and apparently different protein-substrate
      interactions that have a "tuning effect" on the electronic and redox properties
      of bound p-cresol and the covalently bound FAD. The conformational change in the
      segment in the cofactor-binding site is induced by a small rearrangement in the
      flavoprotein-cytochrome interface region of the flavoprotein.

PMID- 15723541
TI  - Kinetic and crystallographic analysis of active site mutants of Escherichia coli
      gamma-aminobutyrate aminotransferase.
AB  - The E. coli isozyme of gamma-aminobutyrate aminotransferase (GABA-AT) is a
      tetrameric pyridoxal phosphate-dependent enzyme that catalyzes transamination
      between primary amines and alpha-keto acids. The roles of the active site
      residues V241, E211, and I50 in the GABA-AT mechanism have been probed by site
      directed mutagenesis. The beta-branched side chain of V241 facilitates formation
      of external aldimine intermediates with primary amine substrates, while E211
      provides charge compensation of R398 selectively in the primary amine half
      reaction and I50 forms a hydrophobic lid at the top of the substrate binding
      site. The structures of the I50Q, V241A, and E211S mutants were solved by X-ray
      crystallography to resolutions of 2.1, 2.5, and 2.52 A, respectively. The
      structure of GABA-AT is similar in overall fold and active site structure to that
      of dialkylglycine decarboxylase, which catalyzes both transamination and
      decarboxylation half-reactions in its normal catalytic cycle. Therefore, an
      attempt was made to convert GABA-AT into a decarboxylation-dependent
      aminotransferase similar to dialkylglycine decarboxylase by systematic mutation
      of E. coli GABA-AT active site residues. Two of the twelve mutants presented,
      E211S/I50G/C77K and E211S/I50H/V80D, have approximately 10-fold higher
      decarboxylation activities than the wild-type enzyme, and the E211S/I50H/V80D has
      formally changed the reaction specificity to that of a decarboxylase.

PMID- 15723542
TI  - Local conformational changes induced in B-DNA by ethidium intercalation.
AB  - Structural effects of binding the intercalating drug ethidium bromide (EtBr) to
      160 base pair (bp) fragments of nucleosomal calf thymus DNA have been probed by
      the method of Raman difference spectroscopy. With the use of a near-infrared
      (NIR) laser source to excite the Raman spectrum at 752 nm, vibrational signatures
      of both the EtBr intercalant and DNA target have been identified in spectra of
      the drug-DNA complexes. Analysis of the results obtained on complexes consisting
      of 1 EtBr bound/10 bp leads to the following conclusions: (i) Raman markers
      diagnostic of DNA phosphodiester conformation are converted from the B type to
      the A type with EtBr binding, commensurate with the proportion of ethidium-bound
      nucleotides in the complex. (ii) Ethidium binding converts deoxynucleoside sugar
      puckers from the C2'-endo to the C3'-endo conformation, also consistent with
      binding stoichiometry. Both pyrimidine and purine deoxynucleoside sugar puckers
      are perturbed by the phenanthridinium ring intercalation. (iii) Phenanthridinium
      insertion between bases is accomplished with no apparent change in
      hypochromicities of purine or pyrimidine Raman markers, indicating that base
      phenanthridinium interactions provide compensatory hypochromic effects. (iv)
      Novel Raman markers of helix unwinding have been identified and assigned
      primarily to methylene deformation modes of the deoxyribosyl C2'H(2) and C5'H(2)
      groups. The present study provides new insights into drug-DNA recognition in
      solution and demonstrates the feasibility of NIR-Raman spectroscopy for
      structural studies of highly chromophoric DNA complexes.

PMID- 15723543
TI  - Initiation of repair of DNA-polypeptide cross-links by the UvrABC nuclease.
AB  - Although the biochemical pathways that repair DNA-protein cross-links have not
      been clearly elucidated, it has been proposed that the partial proteolysis of
      cross-linked proteins into smaller oligopeptides constitutes an initial step in
      removal of these lesions by nucleotide excision repair (NER). To test the
      validity of this repair model, several site-specific DNA-peptide and DNA-protein
      cross-links were engineered via linkage at (1) an acrolein-derived gamma
      hydroxypropanodeoxyguanosine adduct and (2) an apurinic/apyrimidinic site, and
      the initiation of repair was examined in vitro using recombinant proteins UvrA
      and UvrB from Bacillus caldotenax and UvrC from Thermotoga maritima. The
      polypeptides cross-linked to DNA were Lys-Trp-Lys-Lys, Lys-Phe-His-Glu-Lys-His
      His-Ser-His-Arg-Gly-Tyr, and the 16 kDa protein, T4 pyrimidine dimer
      glycosylase/apurinic/apyrimidinic site lyase. For the substrates examined, DNA
      incision required the coordinated action of all three proteins and occurred at
      the eighth phosphodiester bond 5' to the lesion. The incision rates for DNA
      peptide cross-links were comparable to or greater than that measured on
      fluorescein-adducted DNA, an excellent substrate for UvrABC. Incision rates were
      dependent on both the site of covalent attachment on the DNA and the size of the
      bound peptide. Importantly, incision of a DNA-protein cross-link occurred at a
      rate approximately 3.5-8-fold slower than the rates observed for DNA-peptide
      cross-links. Thus, direct evidence has been obtained indicating that (1) DNA
      peptide cross-links can be efficiently incised by the NER proteins and (2) DNA
      peptide cross-links are preferable substrates for this system relative to DNA
      protein cross-links. These data suggest that proteolytic degradation of DNA
      protein cross-links may be an important processing step in facilitating NER.

PMID- 15723544
TI  - An aminoacyl-tRNA synthetase with a defunct editing site.
AB  - Many aminoacyl-tRNA synthetases (aaRSs) contain two active sites, a synthetic
      site catalyzing aminoacyl-adenylate formation and tRNA aminoacylation and a
      second editing or proofreading site that hydrolyzes misactivated adenylates or
      mischarged tRNAs. The combined activities of these two sites lead to rigorous
      accuracy in tRNA aminoacylation, and both activities are essential to LeuRS and
      other aaRSs. Here, we describe studies of the human mitochondrial (hs mt) LeuRS
      indicating that the two active sites of this enzyme have undergone functional
      changes that impact how accurate aminoacylation is achieved. The sequence of the
      hs mt LeuRS closely resembles a bacterial LeuRS overall but displays significant
      variability in regions of the editing site. Studies comparing Escherichia coli
      and hs mt LeuRS reveal that the proofreading activity of the mt enzyme is
      disrupted by these sequence changes, as significant levels of Ile-tRNA(Leu) are
      formed in the presence of high concentrations of the noncognate amino acid.
      Experiments monitoring deacylation of Ile-tRNA(Leu) and misactivated adenylate
      turnover revealed that the editing active site is not operational. However, hs mt
      LeuRS has weaker binding affinities for both cognate and noncognate amino acids
      relative to the E. coli enzyme and an elevated discrimination ratio. Therefore,
      the enzyme achieves fidelity using a more specific synthetic active site that is
      not prone to errors under physiological conditions. This enhanced specificity
      must compensate for the presence of a defunct editing site and ensures
      translational accuracy.

PMID- 15723545
TI  - Directing the outcome of deoxyribozyme selections to favor native 3'-5' RNA
      ligation.
AB  - Previous experiments have identified numerous RNA ligase deoxyribozymes, each of
      which can synthesize either 2',5'-branched RNA, linear 2'-5'-linked RNA, or
      linear 3'-5'-linked RNA. These products may be formed by reaction of a 2'
      hydroxyl or 3'-hydroxyl of one RNA substrate with the 5'-triphosphate of a second
      RNA substrate. Here the inherent propensities for nucleophilic reactivity of
      specific hydroxyl groups were assessed using RNA substrates related to the
      natural sequences of spliceosome substrates and group II introns. With the
      spliceosome substrates, nearly half of the selected deoxyribozymes mediate a
      ligation reaction involving the natural branch-point adenosine as the
      nucleophile. In contrast, mostly linear RNA is obtained with the group II intron
      substrates. Because the two sets of substrates differ at only three nucleotides,
      we conclude that the location of the newly created ligation junction in DNA
      catalyzed branch formation depends sensitively on the RNA substrate sequences.
      During the experiment that led primarily to branched RNA, we abruptly altered the
      selection strategy to demand that the deoxyribozymes create linear 3'-5' linkages
      by introducing an additional selection step involving the 3'-5'-selective 8-17
      deoxyribozyme. Although no 3'-5' linkages (<or=1%) were detectable in the pool
      products at the point that the 3'-5' selection pressure was applied,
      deoxyribozymes that specifically create 3'-5' linkages quickly emerged within a
      few selection rounds. Our success in obtaining 3'-5' linkages via this approach
      shows that the outcome of deoxyribozyme selection experiments can be dramatically
      redirected by strategic changes in the selection procedure, even at a late stage.
      These results relate to natural selection, in which abrupt environmental
      variation can provide a rapid change in selection pressure. Linear 3'-5' RNA
      linkages are an important practical objective because the native backbone is
      desirable in site-specifically modified ribozymes assembled by ligation.
      Therefore, this new approach to obtain 3'-5'-selective RNA ligase deoxyribozymes
      is particularly important for ongoing selection efforts.

PMID- 15723546
TI  - Two-state folding of horse ferrocytochrome c: analyses of linear free energy
      relationship, chevron curvature, and stopped-flow burst relaxation kinetics.
AB  - Ferrocytchrome c is a classic two-state fast folder. This assurance comes from
      extensive equilibrium and kinetic folding studies carried out under strictly
      anaerobic conditions at 22 degrees C. Conventional guanidine hydrochloride
      (GdnHCl)-induced unfolding transitions monitored by the use of a sizable set of
      optical probes do not reveal the accumulation of any intermediate to a detectable
      level. The GdnHCl dependence of unfolding free energy (DeltaG(D)) is linear over
      the full range of the denaturant concentration. The GdnHCl folding chevron is
      characterized by curvatures in both folding and unfolding limbs. However,
      refolding rates as a function of urea in the presence of different concentrations
      of GdnHCl yield m(++)f values (the kinetic m-value) that are quantitatively
      identical. This result, analyzed in terms of the denaturant dependence of the
      difference in the extent of solvent exposure between a relatively fixed
      transition state and the preceding state involved in the transition, suggests
      that the chevron curvature is not related to differential accumulation of a
      folding intermediate with varying concentration of GdnHCl in the refolding
      medium. Denaturant dependence of stopped-flow burst signals recorded in normal
      refolding experiments (pH 7, 22 degrees C) is essentially identical with that
      recorded in simulating experiments in which the protein stays steadily unfolded
      even in the denaturant-diluted medium (pH 1.5-2, 22 or 43 degrees C depending on
      the use of urea or GdnHCl), and they match the denaturant dependence of
      equilibrium signals for the unfolded protein. The results demonstrate that the
      burst phase does not entail an early folding intermediate. Rather, the folding
      kinetics are essentially two-state. These results are central to the
      phenomenological description of protein folding.

PMID- 15723547
TI  - Protein folding in classical perspective: folding of horse cytochrome c.
AB  - Proteins meet with the stipulations of Levinthal. Two test tube variants of
      ferrocytochrome c (ferrocyt c) whose thermodynamic stabilities are vastly
      different refold to the same global minimum under a given final native condition,
      and they do so quickly at rates that do not reflect a strong dependence on the
      thermodynamic driving force. The transition-state ensemble is more unfolded-like,
      and the folding barrier offered is energetically sizable. The experiments involve
      neutral- (pH 7) and alkaline ferrocyt c pH (12.7), whose aqueous stabilities are
      18 (+/-0.3) and 3 (+/-0.5) kcal mol(-)(1), respectively. But the large disparity
      in thermodynamic stability is not strongly reflected in their refolding rates.
      Cross-pH studies, where GdnHCl-unfolded states of neutral- and alkaline ferrocyt
      c are allowed to refold to the same final pH and denaturant concentration,
      indicate that the refolding rates are largely independent of the stability,
      configuration, ionization, and solvation of the initial unfolded state. Also,
      burst relaxation signals in cross-pH refolding runs show the same quantitative
      dependence on GdnHCl, suggesting that the earliest relaxation or reconfiguration
      of the chains must be the same and is independent of the initial equilibrium
      unfolded state. Analyses along the classical line indicate an early transition
      state where much less than a third of the protein surface that is buried in the
      native state becomes buried. The barrier energy is of the order of 10 k(B)T. The
      results, apparently inconsistent with the predictions of the funnel model, afford
      a mechanistic description of folding in which the folding time of small single
      domain proteins is set by the time needed for the denatured polypeptide to search
      find a nativelike topology.

PMID- 15723548
TI  - Oleate-mediated stimulation of microsomal triglyceride transfer protein (MTP)
      gene promoter: implications for hepatic MTP overexpression in insulin resistance.
AB  - Hepatic lipoprotein overproduction in a fructose-fed hamster model of insulin
      resistance was previously shown to be associated with a significant elevation of
      intracellular mass of microsomal triglyceride transfer protein (MTP) and elevated
      plasma levels of free fatty acids (FFA). Here, we further establish that fructose
      feeding and development of an insulin resistant state result in higher levels of
      MTP mRNA, protein mass, and lipid transfer activity. MTP protein mass was
      increased in fructose-fed hamster hepatocytes to 161 +/- 35.8% of control (p <
      0.05), while MTP mRNA levels and MTP lipid transfer activity were increased to
      147.5 +/- 30.8% (p < 0.05) and 177.5 +/- 14.5% (p < 0.05) of control levels,
      respectively. To identify underlying mechanisms, we also investigated the
      potential link between enhanced FFA flux and hepatic MTP gene expression. Direct
      modulation of MTP gene transcription by fatty acids was investigated by
      transfecting HepG2 cells with a reporter (luciferase) construct containing
      various base pair regions of the human MTP promoter including pMTP124 (with the
      sterol response element (SRE)), pMTP116, pMTP109 and pMTP100 (no SRE), and
      pMTP124SREKO (SRE sequences mutated). Treatment of HepG2 cells with oleic acid
      (360 muM) significantly increased luciferase activities in cells transfected with
      pMTP124 (136.6 +/- 11.0%, p < 0.05) and pMTP124SREKO (153.9 +/- 11.1%, p < 0.01)
      compared with control. Luciferase activity was also increased in a time and dose
      dependent manner in the presence of oleic acid when transfected with pMTP124SREKO
      but not pMTP109 and pMTP100. Furthermore, long-term oleic acid treatment of HepG2
      cells (10 days) induced higher levels of MTP mRNA (p < 0.05) confirming
      transcriptional stimulation of the MTP gene by oleic acid. In contrast,
      palmitate, arachidonic acid or linoleic acid did not significantly stimulate
      pMTP124 or pMTP124SREKO luciferase activity (p > 0.05). These data demonstrate
      that (1) MTP gene transcription may be directly up-regulated by oleic acid; (2)
      up-regulation of MTP gene transcription by oleic acid is SRE sequence
      independent; and (3) the sequence -116 to -109 in the MTP promoter region is
      essential for oleic acid-mediated stimulation. Stimulation of MTP gene expression
      may be a novel mechanism by which certain FFAs can induce hepatic lipoprotein
      secretion in insulin resistant states.

PMID- 15723549
TI  - Chromophore exchange in the LOV2 domain of the plant photoreceptor phototropin1
      from oat.
AB  - Phototropins are a family of plant photoreceptors mediating blue light responses
      such as phototropism, leaf expansion, chloroplast relocation, and stomatal
      opening. Characteristic for phototropins are two LOV domains which, when
      expressed in heterologous systems, each carry a single flavin mononucleotide
      (FMN) chromophore. Here we describe removal of FMN from the LOV2 domain of Avena
      sativa using a hydrophobic matrix and successful incorporation of flavin adenine
      dinucleotide (FAD), riboflavin, and 5'-malonyl-riboflavin into the resulting
      apoprotein; 5-deaza-FMN was not incorporated under the applied conditions. The
      chromoproteins reconstituted with the various flavins showed absorption spectra
      and photocycle almost identical to those of the native LOV2 domain and that
      reconstituted with FMN except for the kinetics: LOV2-riboflavin and LOV2-5'
      malonyl-riboflavin showed more rapid regeneration in the dark. LOV2-FAD can be
      hydrolyzed to LOV2-FMN with phosphodiesterase, indicating that the adenosine part
      extrudes from the protein. Together with the data from the X-ray structure
      (Crosson, S., and Moffat, K. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 2995-3000),
      the results allow us to decide which of the chromophore-protein interactions are
      essential for the reconstitution process.

PMID- 15723550
TI  - Investigating the cause of the alkaline transition of phytocyanins.
AB  - The phytocyanins are a family of plant cupredoxins that have been subdivided into
      the stellacyanins, plantacyanins, and uclacyanins. All of these proteins possess
      the typical type 1 His(2)Cys equatorial ligand set at their mononuclear copper
      sites, but the stellacyanins have an axial Gln ligand in place of the weakly
      coordinated Met of the plantacyanins, uclacyanins, and most other cupredoxins.
      The stellacyanins exhibit altered visible, EPR, and paramagnetic (1)H NMR spectra
      at elevated pH values and also modified reduction potentials. This alkaline
      transition occurs with a pK(a) of approximately 10 [Dennison, C., Lawler, A. T.
      (2001) Biochemistry 40, 3158-3166]. In this study we demonstrate that the
      alkaline transition has a similar influence on the visible, EPR, and paramagnetic
      NMR spectra of cucumber basic protein (CBP), which is a plantacyanin. The
      mutation of the axial Gln95 ligand into a Met in umecyanin (UMC), the
      stellacyanin from horseradish roots, and the axial Met89 into a Gln in CBP have
      very limited, yet similar, influence on the pK(a) for the alkaline transition as
      judged from alterations in visible spectra. The complete removal of the axial
      ligand in the Met89Val variant of CBP results in a slightly larger decrease in
      the pK(a) for this effect, but similar spectral alterations are still observed at
      elevated pH. Thus, the axial Gln ligand is not the cause of the alkaline
      transition in Cu(II) stellacyanins, and alterations in the active site structures
      of the phytocyanins have a limited effect on this feature. The conserved Lys
      residue found adjacent to the axial ligand in the sequences of all phytocyanins,
      and implicated as the trigger for the alkaline transition, has been mutated to an
      Arg in UMC. The influence of increasing pH on the spectroscopic properties of
      Lys96Arg UMC is almost identical to those of the wild type protein, and thus,
      this residue is not responsible for the alkaline transition. However, a
      positively charged residue in this position seems to be important for the correct
      folding of UMC. Other possible triggers for the effects seen in the phytocyanins
      at elevated pH are discussed along with the relevance of the alkaline transition.

PMID- 15723551
TI  - Structure of the higher plant light harvesting complex I: in vivo
      characterization and structural interdependence of the Lhca proteins.
AB  - We have investigated the structure of the higher plant light harvesting complex
      of photosystem I (LHCI) by analyzing PSI-LHCI particles isolated from a set of
      Arabidopsis plant lines, each lacking a specific Lhca (Lhca1-4) polypeptide.
      Functional antenna size measurements support the recent finding that there are
      four Lhca proteins per PSI in the crystal structure [Ben-Shem, A., Frolow, F.,
      and Nelson, N. (2003) Nature 426, 630-635]. According to HPLC analyses the number
      of pigment molecules bound within the LHCI is higher than expected from
      reconstitution studies or analyses of isolated native LHCI. Comparison of the
      spectra of the particles from the different lines reveals chlorophyll absorption
      bands peaking at 696, 688, 665, and 655 nm that are not present in isolated PSI
      or LHCI. These bands presumably originate from "gap" or "linker" pigments that
      are cooperatively coordinated by the Lhca and/or PSI proteins, which we have
      tentatively localized in the PSI-LHCI complex.

PMID- 15723553
TI  - Swapping core residues in homologous proteins swaps folding mechanism.
AB  - Rat intestinal fatty acid binding protein (IFABP) displays an intermediate with
      little if any secondary structure during unfolding, while the structurally
      homologous rat ileal lipid binding protein (ILBP) displays an intermediate during
      unfolding with nativelike secondary structure. Double-jump experiments indicate
      that these intermediates are on the folding path for each protein. To test the
      hypothesis that differences in the number of buried hydrophobic atoms in a
      folding initiating site are responsible for the different types of intermediates
      observed for these proteins, two mutations (F68C-IFABP and C69F-ILBP) were made
      that swapped a more hydrophobic residue for a more hydrophilic residue in the
      respective cores of these two proteins. F68C-IFABP followed an unfolding path
      identical to that of WT-ILBP with an intermediate that showed nativelike
      secondary structure, whereas C69F-ILBP followed an unfolding path that was
      identical to that of WT-IFABP with an intermediate that lacked secondary
      structure. Further, a hydrophilic residue was introduced at an identical
      hydrophobic structural position in both proteins (F93S-IFABP and F94S-ILBP).
      Replacement of phenylalanine with serine at this site led to the appearance of an
      intermediate during refolding that lacked secondary structure for both proteins
      that was not detected for either parental protein. Altering the chemical
      characteristics and/or size of residues within an initiating core of hydrophobic
      interactions is critical to the types of intermediates that are observed during
      the folding of these proteins.

PMID- 15723552
TI  - pH and kinetic isotope effects on sarcosine oxidation by N-methyltryptophan
      oxidase.
AB  - N-Methyltryptophan oxidase (MTOX), a flavoenzyme from Escherichia coli, catalyzes
      the oxidative demethylation of secondary amino acids such as N-methyltryptophan
      or N-methylglycine (sarcosine). MTOX is one of several flavin-dependent amine
      oxidases whose chemical mechanism is still debated. The kinetic properties of
      MTOX with the slow substrate sarcosine were determined. Initial rate data are
      well-described by the equation for a ping-pong kinetic mechanism, in that the
      V/K(O)()2 value is independent of the sarcosine concentration at all accessible
      concentrations of oxygen. The k(cat)/K(sarc) pH profile is bell-shaped, with
      pK(a) values of 8.8 and about 10; the latter value matches the pK(a) value of the
      substrate nitrogen. The k(cat) pH profile exhibits a single pK(a) value of 9.1
      for a group that must be unprotonated for catalysis. There is no significant
      solvent isotope effect on the k(cat)/K(sarc) value. With N-methyl-(2)H(3)-glycine
      as the substrate, there is a pH-independent kinetic isotope effect on k(cat),
      k(cat)/K(sarc), and the rate constant for flavin reduction, with an average value
      of 7.2. Stopped-flow spectroscopy with both the protiated and deuterated
      substrate failed to detect any intermediates between the enzyme-substrate complex
      and the fully reduced enzyme. These results are used to evaluate proposed
      chemical mechanisms.

PMID- 15723554
TI  - Structural characterization of the filamentous bacteriophage PH75 from Thermus
      thermophilus by Raman and UV-resonance Raman spectroscopy.
AB  - The filamentous bacteriophage PH75, which infects the thermophile T.
      thermophilus, assembles in vivo at 70 degrees C and is stable to at least 90
      degrees C. Although a high-resolution structure of PH75 is not available, the
      virion is known to comprise a closed single-stranded (ss) DNA circle of 6500
      nucleotides sheathed by a capsid comprising 2700 copies of a 46-residue subunit
      (pVIII). Here, we employ Raman and UV-resonance Raman (UVRR) spectroscopy to
      identify structural details of the pVIII and DNA constituents of PH75 that may be
      related to the high thermostability of the native virion assembly. Analysis of
      the Raman amide I and amide III signatures reveals that the capsid subunit
      secondary structure is predominantly (87%) alpha-helical but contains a
      significant number of residues (6 +/- 1 or 13 +/- 3%) differing from the
      canonical alpha-helix. This minor structural component is not apparent in capsid
      subunits of the mesophilic filamentous phages, fd, Pf1, and Pf3, previously
      examined at similar spectral resolution. The Raman signature of PH75 also differs
      from those of fd, Pf1, and Pf3 by virtue of an unusual alanine marker (898 cm(
      )(1) band), which is attributed to C(alpha)-H hydrogen-bond donation by subunit
      Ala residues. Because alanines of the PH75 subunit occur primarily within sXXXs
      motifs (where s is a small side chain, e.g. Gly, Ala, Ser), and because the
      occurrence of such motifs in alpha-helices is believed to thermostabilize
      interhelix associations via C(alpha)-H...O interactions [G. Kleiger et al. (2002)
      Biochemistry 41, 5990-5997], we propose that such hydrogen bonding may explain
      both the alanyl and amide I/III markers of PH75 capsid subunits and that C(alpha)
      H...O interactions may serve as a significant source of virion
      thermostabilization. Raman and UVRR signatures of PH75 are also distinguished
      from those of fd, Pf1, and Pf3 by several marker bands that are indicative of
      hydrophilic Trp and Tyr environments, including hydrogen bonding interactions of
      aromatic ring substituents. These interactions are likewise proposed as
      contributors to the high thermostability of PH75 vis-a-vis fd, Pf1, and Pf3.
      Finally, PH75 is the only filamentous phage exhibiting UVRR markers diagnostic of
      a highly base-stacked ssDNA genome incorporating the low energy C2'-endo/anti
      deoxynucleoside conformation. The present results suggest that both intersubunit
      interactions and genome organization contribute to the enhanced thermostability
      of PH75 relative to mesophilic filamentous bacteriophages.

PMID- 15723555
TI  - Structural investigation into the differential target enzyme regulation displayed
      by plant calmodulin isoforms.
AB  - The conserved calmodulin (CaM) isoform SCaM-1 and the divergent SCaM-4 from
      soybean bind to many of the same target enzymes, but differentially activate or
      competitively inhibit them. Class 1 target enzymes are activated by both calcium
      (Ca(2+))-bound SCaM-1 (Ca(2+)-SCaM-1) and Ca(2+)-bound SCaM-4 (Ca(2+)-SCaM-4),
      while class 2 enzymes are activated by Ca(2+)-SCaM-1 but competitively inhibited
      by Ca(2+)-SCaM-4, and class 3 enzymes are activated by Ca(2+)-SCaM-4 but
      competitively inhibited by Ca(2+)-SCaM-1. To determine whether these differences
      can be attributed to unique interactions with the CaM-binding domains (CaMBD) of
      these enzymes, we have studied the binding of each protein to peptides derived
      from the CaMBD of a representative target enzyme from each of these three
      classes. Using a combination of NMR spectroscopy and isothermal titration
      calorimetry, we demonstrate that the N- and C-domains of either Ca(2+)-SCaM bind
      to each peptide to form structurally compact complexes driven by the burial of
      hydrophobic surfaces. Interestingly, the interactions with the CaMBD peptides
      from classes 1 and 2 are similar for the two proteins; however, binding to the
      peptide from class 3 is structurally and thermodynamically distinct for Ca(2+)
      SCaM-1 and -4. We also demonstrate that both calcium-free SCaM-1 (apo-SCaM-1) and
      calcium-free SCaM-4 (apo-SCaM-4) bind to the CaMBD from cyclic nucleotide
      phosphodiesterase, and that the interactions are similar to each other and to the
      interactions with apo-mammalian CaM. Therefore, the apo-SCaMs are also capable of
      binding to the same target enzymes, which could provide an additional mechanism
      for CaM-dependent signaling in plants.

PMID- 15723556
TI  - Use of binding enthalpy to drive an allosteric transition.
AB  - The Escherichia coli biotin repressor is an allosteric DNA binding protein and is
      activated by the small molecule bio-5'-AMP. Binding of this small molecule
      promotes transcription repression complex assembly between the repressor and the
      biotin operator of the biotin biosynthetic operon. The ability of the adenylate
      to activate the assembly process reflects its effect on biotin repressor
      dimerization. Thus concomitant with small molecule binding the free energy of
      repressor dimerization becomes more favorable by approximately -4 kcal/mol. The
      structural, dynamic, and energetic changes in the repressor monomer that
      accompany allosteric activation are not known. In this work the thermodynamics of
      binding of four allosteric activators to the repressor have been characterized by
      isothermal titration calorimetry. While binding of two of the effectors results
      in relatively modest activation of the dimerization process, binding of the other
      two small molecules, including the physiological effector, leads to large changes
      in repressor dimerization energetics. Results of the calorimetric measurements
      indicate that strong effector binding is accompanied by an enthalpically costly
      transition in the protein. This transition is "paid for" by the enthalpy that
      would have otherwise been realized from the formation of noncovalent bonds
      between the ligand and repressor monomer.

PMID- 15723558
TI  - Control of the mycoplasma epidemic.

PMID- 15723559
TI  - Feeder cell density--a key parameter in human embryonic stem cell culture.
AB  - A key issue in human embryonic stem (ES) cell culture that has largely been
      ignored is the high degree of variability in the murine embryonic fibroblast
      (MEF) feeder cell density, which has been reported by different studies and
      protocols. Presumably, too low a feeder cell density would result in insufficient
      levels of secreted factors, extracellular matrix, and cellular contacts provided
      by the feeder cells for the maintenance of human ES cells in the undifferentiated
      state. Too high a feeder cell density, on the other hand, may result in a more
      rapid depletion of nutrients and oxygen within the in vitro culture milieu, as
      well as physically hinder the attachment and growth of ES colonies during serial
      passaging. Preliminary investigations by our group revealed that an elevated MEF
      cell density of 32,000 cells/cm2, above the recommended value of 20,000
      cells/cm2, appeared to be highly detrimental to the attachment and growth of
      serially passaged ES colonies of the H9 line (WiCell Research Institute Inc.,
      Wilmington, MA, USA). At the edge of ES colonies that have attached to the higher
      density feeder layer (32,000 cells/cm2), the ES cells appear to stack up to form
      a "bulge." This was not observed under the recommended feeder cell density of
      20,000 cells/cm2. By contrast, other established ES cell lines are routinely
      propagated at much higher feeder densities of 60,000 to 70,000 cells/cm2. This
      report briefly discusses the issue of MEF feeder cell density in relation to our
      preliminary observations, and the results of other studies.

PMID- 15723560
TI  - Cell growth in vitro directed by handmade patterns.
AB  - In this report, we show how the in vitro model of mechanically injured confluent
      monolayers of cultured mammalian cells, consisting in denudation by gentle
      scraping of areas in the monolayer, can be extended to obtain patterned cell
      cultures without using preadded attaching matrices. This work was done with a
      sinusoidal endothelial liver cell line. Patterns for cell growth were drawn in
      confluent monolayers by cell detaching with the aid of pipette tips followed by
      reincubation of the culture. In one or some d, acellular patterns were closed by
      cell migration and proliferation. For unveiling the pattern formed by migration
      and cell duplication, an enzymatic digestion with trypsin-collagenase solution
      was applied; after some min, only the migrating and younger cells filling the
      previous acellular pattern remained attached to the dish, and the now cellular
      pattern was clearly depicted. After stopping and recovering from the enzymatic
      treatment, the culture was ready for starting studies such as those related to
      migration, proliferation, cell-cell interactions. This method allows us to create
      simple and complex patterns, does not require preparation of the dishes with
      attaching matrices, and extracellular matrices in acellular areas are absent
      because of the enzymatic treatment, thus, potentially having many applications in
      cell culture techniques.

PMID- 15723561
TI  - Restructuring dynamics of DU 145 and LNCaP prostate cancer spheroids.
AB  - Neoplastic cells acquire multidrug resistance as they assemble into multicellular
      spheroids. Image analysis and Monte Carlo simulation provided an insight into the
      adhesion and motility events during spheroid restructuring in liquid-overlay
      culture of DU 145 and LNCaP human prostate cancer cells. Irregularly shaped, two
      dimensional aggregates restructured through incremental cell movements into three
      dimensional spheroids. Of the two cultures examined, restructuring was more
      pronounced for DU 145 aggregates. Motile DU 145 cells formed spheroids with a
      minimum cell overlay of 30% for 25-mers as estimated by simulation versus 5% for
      adhesive LNCaP cells in aggregates of the same size. Over 72 h, the texture ratio
      increased from 0.55 +/- 0.05 for DU 145 aggregates with projected areas exceeding
      2000 microm2 to a value approaching 0.75 +/- 0.02 (P < 0.05). For LNCaP
      aggregates of comparable size, the increase in texture ratio was more modest,
      less than 15% during the same time period (P < 0.05). Combined, these data
      suggest that motility events govern the overall rate of spheroid restructuring.
      This information has application to the chemosensitization of solid tumors and
      kinetic modeling of spheroid production.

PMID- 15723562
TI  - Improved enzymatic isolation of fibroblasts for the creation of autologous skin
      substitutes.
AB  - The number of medical applications using autologous fibroblasts is increasing
      rapidly. We investigated thoroughly the procedure to isolate cells from skin
      using the enzymatic tissue dissociation procedure. Tissue digestion efficiency,
      cell viability, and yield were investigated in relation to size of tissue
      fragments, digestion volume to tissue ratio, digestion time, and importance of
      other protease activities present in Clostridium histolyticum collagenase (CHC)
      (neutral protease, clostripain, and trypsin). The results showed that digestion
      was optimal with small tissue fragments (2-3 mm3) and with volumes tissue ratios
      > or =2 ml/g tissue. For incubations < or =10 h, the digestion efficiency and
      cell isolation yields were significantly improved by increasing the collagenase,
      neutral protease, or clostripain activity, whereas trypsin activity had no
      effects. However, a too high proteolytic activity of one of the proteases present
      in CHC digestion solution or long exposure times interfered with cell viability
      and cell culture yields. The optimal range of CHC proteases activities per
      milliliter digestion solutions was determined for digestions < or =10 h
      (collagenase 2700-3900 Mandl U/ml, neutral protease 5100-10,000 caseinase U/ml,
      and clostripain 35-48 BAEE U/ml) and for longer digestions (>14 h) (collagenase
      1350- 3000 U/ml, neutral protease 2550-7700 U/ml, and clostripain 18-36 U/ml).
      Using these conditions, a maximum fibroblast expansion was achieved when isolated
      cells were seeded at 1 x 10(4) cells/cm2. These results did not only allow
      selection of optimal CHC batches able to digest dermal tissue with an high cell
      viability but also significantly increased the fibroblast yields, enabling us to
      produce autologous dermal tissue in a clinically acceptable time frame of 3 wk.

PMID- 15723563
TI  - Establishment of a long-term culture system for rat colon epithelial cells.
AB  - The aim of this study was to establish a long-term culture system for rat colon
      epithelial cells. Colonic crypts were isolated by incubating a 4-cm-long rat
      colon segment cut longitudinally with an ethylenediaminetetraacetic acid
      [disodium salt]-containing buffer, taken up in conditioned medium from the normal
      rat kidney fibroblast cell line NRK (i.e., the supernatant of pure NRK cultures),
      directly plated on mitomycin C-treated NRK cells and subcultured with conditioned
      medium from NRK cells. Cells started to migrate out of the crypts shortly after
      plating them on NRK feeder layers. Some of the crypts fell apart during the
      isolation procedure, whereas the vast majority of them did it within 1 to 2 h
      after plating. The cells proliferated extremely slowly but continuously over a
      period of 4 mo and were epithelial because they expressed cytokeratin 19 and were
      stained by crystal violet at pH 2.8. In conclusion, the experimental system
      described in this study allows to maintain rat colon epithelial cells for up to 4
      mo in culture and can be used to study the effects of a variety of tumor
      modulating factors on growth and gene expression of normal colon epithelial cells
      in vitro.

PMID- 15723565
TI  - Recombinant alkaline serine protease II degrades scrapie isoform of prion
      protein.
AB  - An efficient Escherichia coli expression system for the production of mature-type
      alkaline serine protease II (mASP II) has been constructed. Complementary
      deoxyribonucleic acid-encoding mASP II was inserted into the inducible bacterial
      expression vector pGE-30. After introduction into E. coli, the plasmid was
      expressed by isopropyl-1-thio-beta-D-galactopyranoside, and the recombinant
      product was purified using a Ni-nitrilotriacetic acid column. The purified
      product had the expected NH2-terminal sequence and showed a scrapie isoform of
      prion protein-degrading activity using hamster scrapie 263K prions as a
      substrate.

PMID- 15723564
TI  - Deletions in the DNA-binding domain of the TP53 gene in v-src-transformed chicken
      cells.
AB  - We have examined the chicken TP53 tumor suppressor gene in v-src-transformed
      chicken tumor cells by reverse transcriptase-polymerase chain reaction and
      deoxyribonucleic acid (DNA) sequencing. Initially, we have detected frequent
      deletions of variable length in both DNA-binding and oligomerization domains of
      the TP53 in late as well as early in vitro passages of the chicken tumor cell
      line PR9692. This tumor cell line shows an immortal phenotype and acquires a
      metastatic potential that is unique in our experimental model of v-src-induced
      tumors in congenic chickens. Deletions in TP53 were also detected in an early
      passage of parallel in vivo subculture of the original v-src-induced tumor. In
      this case, tumor cells underwent replicative senescence later in tissue culture.
      Our results suggest that extensive deletions are efficient mechanisms of TP53
      inactivation, occurring as early events during the immortalization of v-src
      transformed chicken cells. Tumor cells with altered TP53 might, however, still be
      susceptible to growth control mechanisms, leading to withdrawal from the mitotic
      cycle in the early stage of the tumor lifeline.

PMID- 15723566
TI  - The UV Index on the Spanish Mediterranean coast.
AB  - An analysis is made of measured ultraviolet erythemal solar radiation (UVER) data
      recorded during the year 2003 by the networks of the Catalan Weather Service and
      the Environment Department of Valencia (both on the Spanish Mediterranean coast).
      Results show a latitudinal variation at sea level, of 3-4% per degree and an
      increase with altitude of 10% per km. Based on these data the UV Index has been
      evaluated for the measuring stations. The maximum experimental value of the UV
      Index was around 9 during the summer, although higher values were recorded at two
      stations, one at the highest elevation and the other at the lowest latitude. The
      annual accumulated doses of irradiation on a horizontal plane have been presented
      as well as the evolution through the year in units of energy, Standard Erythemal
      Doses and Minimum Erythemal Doses according to different phototypes. Lastly, the
      UV Index forecast, determined with a multiple scattering radiative transfer
      model, has been analyzed. Total agreement or only one unit of difference between
      measured and modelled values was found in 94% of cloud-free cases.

PMID- 15723567
TI  - Laser flash photolysis in a O3/Cl2 mixture at 266 nm in a very low-pressure flow
      system.
AB  - The laser flash photolysis in a very low-pressure flow system with mass
      spectrometry detection technique was developed for the study of oxidation
      reactions of chlorofluorocarbons. In this work, we have studied the UV photolysis
      of O3 in the presence of Cl2 at room temperature, which presents two catalytic
      cycles of O3 depletion with efficiencies dependent on the partial pressures in
      the photoreactor. The ozone dissociation was initiated with fourth harmonic
      pulses of a Nd:YAG laser. The detection of the reactants and the final and
      intermediate reaction products was performed with real-time mass spectrometry.
      The variations of the O3, Cl2 and ClO concentration were measured. The equations
      system associated to a proposed kinetic scheme was solved numerically and
      excellent agreement with the experimental results was obtained. The results from
      this work allowed the determination of the wall loss rates of the O(1D), Cl and
      ClO radicals.

PMID- 15723568
TI  - Tissue Doppler and strain-rate imaging in cardiac ultrasound imaging: valuable
      tools or expensive ornaments?

PMID- 15723569
TI  - Statin therapy in heart failure.

PMID- 15723571
TI  - American Heart Association Scientific Sessions 2004: Brain and heart.

PMID- 15723572
TI  - Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with
      perindopril.
AB  - Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme
      inhibitor with high tissue angiotensin-converting enzyme affinity, lowering
      angiotensin II and potentiating bradykinin. Its efficacy, safety and tolerability
      are well established in the treatment of hypertension and heart failure.
      Moreover, large morbidity-mortality trials, such as the EUropean trial on
      Reduction Of cardiac events with Perindopril in stable coronary Artery disease
      (EUROPA) and Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS),
      have shown that antihypertensive treatment with perindopril reduces and prevents
      cardiovascular disease in a large range of patients with vascular diseases,
      whether hypertensive or not. Thus, the outcome of these and other trials support
      the concept of cardiovascular protective properties of angiotensin-converting
      enzyme inhibition with perindopril in addition to the obvious blood-pressure
      lowering effect. Considering its properties and the gathered clinical evidence on
      efficacy and tolerability, perindopril fulfils the criteria of the latest
      guidelines for hypertension and cardiovascular disease management and should
      therefore be considered as a first-line antihypertensive agent, forming a
      consistent part of the comprehensive strategy against hypertension and related
      cardiovascular complications.

PMID- 15723574
TI  - Use of nifedipine in the treatment of hypertension.
AB  - Hypertension is an important modifiable risk factor for cardiovascular disease;
      its prevention and treatment currently represent major health concerns around the
      world, especially in western countries. Effective, well-tolerated drugs such as
      dihydropyridine calcium channel blockers, to be used either alone or in
      combination treatments, play a key role in reducing cardiovascular morbidity and
      mortality. The extended-release formulation of nifedipine given once daily
      provides a relatively constant concentration profile and has proved to be
      effective in reducing blood pressure values. In the International Nifedipine
      gastrointestinal therapeutic system Study: Intervention as a Goal in Hypertension
      Treatment (INSIGHT) study, it was demonstrated that nifedipine confers
      cardiovascular protection as effectively as diuretics in high-risk patients, with
      a smaller incidence of adverse metabolic consequences. Furthermore, two INSIGHT
      substudies demonstrated that nifedipine prevents the progression of carotid
      atherosclerosis and reduces the worsening of coronary calcifications, supporting
      the use of calcium channel blockers in hypertensive patients--especially those at
      high cardiovascular risk. This review discusses the existing clinical evidence
      supporting the use of nifedipine in the treatment of hypertension.

PMID- 15723573
TI  - Alternative parenteral anticoagulation with argatroban, a direct thrombin
      inhibitor.
AB  - Argatroban, a direct thrombin inhibitor, effectively inhibits free and clot-bound
      thrombin without the need of a cofactor and exerts dose-dependent anticoagulant
      effects that are rapidly active and rapidly reversible (elimination half-life: 39
      51 min). Argatroban provides predictable parenteral anticoagulation and is well
      tolerated with an acceptably low bleeding risk in a variety of clinical settings,
      including heparin-induced thrombocytopenia, acute ischemic stroke, percutaneous
      coronary intervention and hemodialysis. This review will discuss the clinical
      pharmacology and utility of argatroban; in particular, clinical trial experiences
      will be discussed in patients with, or at risk of, heparin-induced
      thrombocytopenia (where heparins must be avoided) including those requiring
      hemodialysis or percutaneous coronary intervention, and in patients with acute
      ischemic stroke (where heparins are not generally recommended).

PMID- 15723575
TI  - Role of echocardiography in the contemporary management of chronic heart failure.
AB  - Echocardiography is an excellent noninvasive tool for the assessment of
      ventricular size and both systolic and diastolic function, and it is routinely
      used in patients with heart failure. This review will discuss the role of
      echocardiography in heart failure diagnosis, prognostic assessment and in the
      management of heart failure patients.

PMID- 15723576
TI  - Brain natriuretic peptide in the contemporary management of congestive heart
      failure.
AB  - Brain natriuretic peptide is a cardiac neurohormone that is secreted by the left
      ventricle in response to an increase in wall stress. Brain natriuretic peptide
      has emerged as a neurohormone with multiple roles in heart failure management.
      This review will discuss the role of brain natriuretic peptide in heart failure
      diagnosis, prognostic assessment, screening for asymptomatic left-ventricular
      dysfunction, and in the treatment of heart failure.

PMID- 15723577
TI  - Genetic maneuvers to ameliorate ventricular function in heart failure:
      therapeutic potential and future implications.
AB  - Gene therapy to treat heart failure has evolved into a growing field of
      investigation yielding remarkable results in preclinical models. Whether these
      results will persist in clinical trials remains to be seen. However, researchers
      still face a number of obstacles that need to be overcome before this treatment
      can be employed effectively. Efforts are required to identify better vectors with
      minimal side effects and maximal efficiency and durability. There is also a need
      to develop less invasive and more effective techniques to deliver these vectors.
      This review will discuss different methods to achieve these goals, the various
      pathologic mechanisms that have been targeted so far and those with strong
      potential for use in the future.

PMID- 15723578
TI  - Heart failure in the elderly.
AB  - Heart failure is the most common reason for hospitalization among older adults in
      the USA, and impacts five million people. Most people with heart failure are
      elderly, but in older people the management of the disease is complicated by
      comorbid conditions. Common problems in the elderly, such as dementia, frailty
      and depression, are more common in the elderly heart failure population. This
      review discusses an approach to identifying and managing these problems while
      managing heart failure. A suggested approach to older people with heart failure
      addresses the screening and integration of common geriatric problems into heart
      failure care.

PMID- 15723579
TI  - Cardiac resynchronization therapy for congestive heart failure.
AB  - Cardiac resynchronization represents a novel therapeutic strategy for the
      treatment of congestive heart failure due to systolic dysfunction. Since its
      modest beginnings in the 1990s, cardiac resynchronization therapy has gained
      widespread acceptance as a useful adjunct to pharmacologic therapy for congestive
      heart failure. Randomized trials have consistently shown functional improvement
      in patients with congestive heart failure due to systolic dysfunction, a wide QRS
      complex on electrocardiogram and sinus rhythm, that are treated with cardiac
      resynchronization therapy. This review article will address the rationale,
      mechanisms of action, limitations and appropriate selection of patients for
      cardiac resynchronization therapy.

PMID- 15723580
TI  - Hibernating myocardium in heart failure.
AB  - Ischemic left ventricular systolic dysfunction may result from myocardial
      necrosis or from hypocontractile areas of viable myocardium. In some cases,
      recovery of contractility may occur on revascularization--this reversibly
      dysfunctional tissue is commonly referred to as hibernating myocardium.
      Observational data suggest that revascularization of patients with ischemic left
      ventricular systolic dysfunction and known viable myocardium provides a survival
      benefit over medical therapy. Identification of viable, dysfunctional myocardium
      may be especially worthwhile in deciding which patients with ischemic left
      ventricular systolic dysfunction will benefit from revascularization procedures.
      Randomized, prospective trials evaluating this are currently ongoing. This review
      will provide an overview of the complex pathophysiology of viable, dysfunctional
      myocardium, and will discuss outcomes after revascularization. Of the techniques
      used to determine the presence of hibernating myocardium, functional methods such
      as stress echocardiography and cardiac magnetic resonance appear more specific,
      but less sensitive, than the nuclear modalities, which assess perfusion and
      metabolic activity. Currently, the availability of all methods is variable.

PMID- 15723581
TI  - Noninvasive coronary angiography using computed tomography.
AB  - While noninvasive imaging of the coronary lumen remains challenging, great
      strides have been made with computed tomography. Two variations of computed
      tomography are used in the study of the coronary tree: multislice or
      multidetector computed tomography and electron-beam computed tomography. Both
      have high spatial and temporal resolutions as well as excellent signal-to-noise
      ratios, which allows major branches of the coronary tree to be depicted. Impaired
      image quality, due to dense calcifications and multiple image artifacts including
      coronary artery motion and breathing artifacts, limits the clinical utility of
      noninvasive coronary angiography. Early studies with electron-beam angiography
      demonstrated an overall sensitivity of 85% and specificity of 89% for the
      detection of obstructive coronary artery disease. With early diastolic imaging,
      the sensitivity and specificity increases to 92 and 93%, respectively (rather
      than 80% of the cardiac interbeat interval, where coronary motion is more
      pronounced). Multidetector computed tomography, with improved spatial resolution
      but decreased temporal resolution, produces results that vary depending on the
      equipment. Four-slice scanners have an average sensitivity of only 61%, and only
      38% of patients have all four vessels or 15 segments available for analysis, due
      to both cardiac motion and calcification. Thinner slice collimation with eight
      and 16 slices have allowed for improved detection. Sensitivity and specificity
      improve to 80 and 86%, respectively. Furthermore, the number of assessable
      segments with eight-to 16-slice scanners improves significantly, compared with
      four-slice scanners (85 vs. 73%; p<0.001). If only assessable segments are
      included in analysis, sensitivity and specificity for multidetector-row computed
      tomography improves to nearly 90%. Compared with magnetic resonance imaging, with
      a reported accuracy of 72% in the only multicenter study, computed tomography has
      great promise to become the primary method of noninvasive coronary angiography.

PMID- 15723582
TI  - Trends in myocardial contrast echocardiography: parameteric versus volumetric
      imaging.
AB  - It is now possible to perform myocardial contrast echocardiography at the bedside
      with an intravenous injection of commercially available contrast media. Although
      myocardial contrast echocardiography is a sensitive method for the detection of
      coronary stenosis and myocardial viability, its diagnosis has relied largely on
      the subjective interpretation of regional perfusion by experienced clinicians.
      Thus, quantification of myocardial contrast echocardiography data and displaying
      comprehensive images have been necessary for its routine application. In this
      review, new methods for quantifying or displaying myocardial contrast
      echocardiography parameters will be introduced: firstly, parametric imaging that
      displays the parameters of myocardial blood volume, blood flow velocity and
      myocardial blood flow separately; and secondly, color-coded maps of myocardial
      blood volume established from one myocardial contrast echocardiography image.
      These quantitative techniques can provide comprehensive and easy-to-understand
      images, although the quality of the baseline image remains a critical factor.

PMID- 15723583
TI  - Advances in percutaneous valvular intervention.
AB  - We are entering a new era in the percutaneous treatment of valvular heart
      disease. Novel techniques and devices have given rise to the possible treatment
      of a range of valvular heart diseases that previously necessitated surgical
      therapies, including aortic stenosis, pulmonary regurgitation and mitral
      regurgitation. Despite the enormous potential of these percutaneous therapies,
      enthusiasm needs to be balanced by an understanding of the challenges that need
      to be overcome before such therapies can be widely embraced. This review provides
      a critical assessment of the status of the major developments in percutaneous
      valvular intervention to date, and provides the authors' perspective on the
      current role and future potential of these techniques.

PMID- 15723584
TI  - Free radicals and antioxidants in cardiovascular diseases.
AB  - It has been demonstrated that redox homeostasis is important in the
      pathophysiology of several human diseases, including cardiovascular diseases. In
      this respect, genetic polymorphism, nutritional and environmental factors, age,
      lifestyle and physical activity may account for variable antioxidant defenses,
      which may be more or less effective at counteracting oxidative damage. Since
      accumulating oxidative damage may be associated with several pathologic
      conditions, including different cardiovascular diseases, prevention of oxidative
      stress appears to be a promising approach to improve such diseases. Exercise
      training, diets rich in antioxidants and a good control of blood glucose and
      lipid levels help to strengthen the physiologic antioxidant defense system,
      perhaps coupled to drugs capable of increasing the nitric oxide bioavailability
      and decreasing superoxide production. Within the next few years other therapeutic
      approaches will be available, such as gene therapy, which will prove to be even
      more effective but devoid of several important systemic side effects.

PMID- 15723585
TI  - Photoaptamer chips for clinical diagnostics.

PMID- 15723587
TI  - PLAC test for identification of individuals at increased risk for coronary heart
      disease.
AB  - Recent advances in cardiovascular research point to a critical role of
      inflammatory processes in the etiology of cardiovascular disease. This has led to
      the discovery of novel inflammatory biomarkers, which may be useful as additional
      screening tools for the identification of individuals at increased risk of
      coronary heart disease. One such novel inflammatory biomarker is lipoprotein
      associated phospholipase A(2). This review discusses the recent development of a
      US Food and Drug Administration-approved blood test for lipoprotein-associated
      phospholipase A(2) (PLAC test, diaDexus, Inc.) and its efficacy as a predictive
      biomarker of risk for cardiovascular disease. More specifically, the article
      addresses the potential target group most likely to benefit from this new
      screening test and provides a prospective scenario for its implementation.

PMID- 15723588
TI  - FibroTest-FibroSURE: towards a universal biomarker of liver fibrosis?
AB  - Among the noninvasive alternatives to liver biopsy, several studies have
      demonstrated the predictive value and superior benefit/risk ratio to biopsy of
      two combinations of simple serum biochemical markers in patients infected with
      hepatitis B and C virus. These include FibroTest (BioPredictive) for the
      quantitative assessment of fibrosis, and ActiTest (BioPredictive) for the
      quantitative assessment of necroinflammatory activity (HCV-FibroSURE, LabCorp).
      The possible causes of false negatives and positives are also better identified.
      These tests, which are now available in 12 countries, can facilitate the
      screening and management of the most frequent liver diseases.

PMID- 15723589
TI  - Cytogenetic testing for therapeutic indication in cancer.
AB  - The association of cytogenetic abnormalities with cancer is well established.
      However, due to the historic lack of specific insight into the functional role of
      these anomalies, they have mostly served as diagnostic and/or prognostic
      indicators. Recent developments in chronic myelogenous leukemia and breast cancer
      have raised hopes for specific cytogenetic alterations to serve as therapeutic
      targets. This article reviews the aid provided by molecular diagnostics in these
      exciting developments in the cancer arena.

PMID- 15723590
TI  - Rapid tests for detection of viral markers in blood transfusion.
AB  - Since the early 1990s, rapid tests have been available for detection of HIV
      infection. They were intended for field diagnosis, emergency and home testing. In
      addition, rapid tests for anti-HIV, hepatitis B surface antigen and antihepatitis
      C virus have been used for blood screening in many resource-poor areas to save
      resources and overcome lack of funding, equipment and electrical supply. The
      performance of rapid tests varies widely but some have sensitivity and
      specificity levels that meet standards established by enzyme immunoassays for
      anti-HIV. Compared with genomic detection of hepatitis B virus, hepatitis B
      surface antigen rapid tests and enzyme immunoassays have insufficient
      sensitivity. The clinical consequences of this performance deficit remain to be
      clarified. Anti-hepatitis C virus rapid tests detect chronically infected
      individuals who are viremic, however, further studies are required to fully
      assess their performance. In settings where few blood donations are collected and
      equipment is unavailable, rapid tests provide a flexible, technically undemanding
      and relatively inexpensive approach to ensuring a safer blood supply. When
      utilized for predonation screening in areas of high endemicity of viral markers,
      rapid tests provide the means to limit blood bag wasting, store only clinically
      usable blood and inform and counsel deferred donors. As with any laboratory
      assay, adequate training and sustained quality assurance programs are critical to
      maintain a safe supply of blood. As a means of achieving a safe blood supply,
      rapid tests for viral markers and nucleic acid testing have a place next to
      classic enzyme immunoassays in the definition of strategies that are adapted to a
      setting's epidemiology, the size and type of donor base, equipment, staff
      training and resources.

PMID- 15723591
TI  - Gene expression profiling using RNA extracted from whole blood: technologies and
      clinical applications.
AB  - Gene expression profiling promises to provide an insight into normal biologic and
      pathologic processes with the hope of predicting disease outcome or indicating
      individualized courses of therapy. The entire process for gene expression
      profiling from clinical samples consists of sample collection, transport and
      storage of clinical sample, isolation of nucleic acids, enzymatic modification of
      nucleic acids, detection and data analysis. All steps exert an influence on the
      quality, accuracy and reliability of the final result. A standardization of the
      entire process from sample collection to nucleic acid analysis is therefore
      required in order to achieve reliable gene expression results. After providing a
      general overview of technologies for gene expression profiling and respective
      caveats, this review will focus on clinical applications of blood sample
      profiling.

PMID- 15723592
TI  - Separating human DNA mixtures using denaturing high-performance liquid
      chromatography.
AB  - DNA mixtures represent challenging samples that are rarely amenable to direct DNA
      sequence analysis and many of the strategies available to separate mixtures are
      both labor and time intensive. Denaturing high-performance liquid chromatography
      is an accurate and rapid approach for the detection and scoring of mutations. It
      can also be used to separate DNA mixtures. The technique relies on the
      chromatographic separation of crosshybridization products to isolate the
      individual components of a mixture. By eliminating secondary amplification and
      excessive manipulation prior to sequencing, denaturing high-performance liquid
      chromatography can streamline the analysis of conditions ranging from somatic
      mosaicism, microchimerism and mitochondrial heteroplasmy to evidentiary material
      containing mixtures of DNA encountered in forensic investigations.

PMID- 15723593
TI  - Biomarkers in melanoma: stage III and IV disease.
AB  - The prognosis associated with Stage III melanoma is variable (17-65% 5-year
      survival) and primarily influenced by the number of lymph nodes involved, the
      presence of ulceration in a primary lesion, and the tumor burden present in each
      lymph node. In patients with metastatic (Stage IV) melanoma, the prognosis
      remains dismal (6-18% 5-year survival) and is influenced primarily by the sites
      (and extent) of metastatic involvement. Serum lactate dehydrogenase is the only
      prognostic biomarker useful in metastatic melanoma and it has been incorporated
      into the 2002 American Joint Committee on Cancer tumor, node, metastasis staging
      system. In this review, the known prognostic factors in Stage III and IV melanoma
      are reviewed. Selected investigational therapies and associated biomarkers are
      also discussed.

PMID- 15723594
TI  - Recent developments in the diagnosis and monitoring of HBV infection and role of
      the genetic variability of the S gene.
AB  - Recent developments in the laboratory diagnosis of hepatitis B virus infection
      include the optimization of key serologic markers, including hepatitis B virus
      surface antigen and antihepatitis B virus core antibody, as well as the
      development of automated nucleic acid amplification assays. There is still a lack
      of standardization for nucleic acid amplification assays that are used for the
      monitoring of antiviral therapy and follow-up of chronic infection and the
      clinical significance of hepatitis B virus DNA levels need to be clarified.
      Although highly sensitive automated nucleic acid amplification assays for blood
      donor screening are available, their implementation is still subject to
      discussion and certain countries rejected hepatitis B virus DNA testing for blood
      donation due to poor cost effectiveness. Genetic variability of hepatitis B virus
      constitutes a major challenge for diagnosis of hepatitis B virus infection,
      particularly with regard to hepatitis B virus surface antigen detection,
      antihepatitis B virus surface antigen quantification and nucleic acid
      amplification assays. The performances of hepatitis B virus surface antigen
      enzyme immunoassays in regard to genotype and surface antigen variability need to
      be further improved. Polyclonal antibody-based hepatitis B virus surface antigen
      enzyme immunoassays, although they cannot guarantee 100% sensitivity, demonstrate
      superior S gene mutant recognition to assays using monoclonal capture and tracer
      antibodies. Isolated antihepatitis B virus core reactivity is an unusual but
      frequent result, which requires a test algorithm for resolution and hepatitis B
      virus DNA detection with sensitive nucleic acid amplification assays in order to
      exclude occult hepatitis B virus infection.

PMID- 15723595
TI  - Serum, salivary and tissue proteomics for discovery of biomarkers for head and
      neck cancers.
AB  - Initial clinically oriented applications of emerging proteomic technologies that
      aim to identify biomarkers for head and neck squamous cell carcinoma diagnostics
      have yielded promising results. The development of new proteomic diagnostics
      remains critical for the early detection of head and neck squamous cell carcinoma
      at more treatable stages. Prognostic markers for disease recurrence and treatment
      sensitivities are also required. In this overview of current biomarker
      identification strategies for head and neck squamous cell carcinoma, different
      combinations of mass spectrometry platforms, laser capture microscopy and 2D gel
      electrophoresis procedures are summarized as applied to readily available
      clinical specimens (tissue, blood and saliva). Issues related to assay
      reproducibility, management of large data sets and future improvements in
      clinical proteomics are also addressed.

PMID- 15723596
TI  - Molecular diagnosis of neurogenetic disorders involving trinucleotide repeat
      expansions.
AB  - There are more than 15 known neurogenetic disorders involving trinucleotide
      repeat expansion. Expanded repeats range from small expansions of 20-100 copies
      to larger expansions of up to several thousand units. These dynamic expansions
      result in variability in age of onset, degree of severity and clinical
      presentation. Individuals carrying alleles in the intermediate range, known as
      premutation alleles, are often asymptomatic, but can potentially transmit a
      further expanded allele to his/her offspring. For autosomal dominant adult-onset
      disorders, carriers are asymptomatic prior to disease onset. With current
      molecular tools, it is now possible to determine the presence and number of
      expanded repeats for accurate diagnosis, presymptomatic testing and carrier
      status screening. This review examines some of the current approaches for
      molecular diagnosis and discusses the issues unique to triplet repeat diseases.

PMID- 15723597
TI  - Ligation-mediated rolling-circle amplification-based approaches to single
      nucleotide polymorphism detection.
AB  - Ligation-mediated single nucleotide polymorphism detection coupled with an
      efficient method of signal enhancement, such as rolling-circle amplification,
      hyperbranched rolling-circle amplification or PCR, has provided the foundation
      for the development of variable single nucleotide polymorphism genotyping and
      analyzing methods for different applications. Several methods based on the above
      approaches have been developed, enabling rapid genotyping of a large number of
      single nucleotide polymorphisms directly from a small amount of genomic DNA and
      large-scale multiplex single nucleotide polymorphism (>1000 single nucleotide
      polymorphisms per assay) analysis on microarrays. This review categorizes
      different approaches and describes the principles of each approach for single
      nucleotide polymorphism detection. Possible future research directions including
      the development of optimized methods for analysis of cytologic samples and other
      applications are also discussed.

PMID- 15723598
TI  - RNAi specificity: how big of an issue is it?

PMID- 15723600
TI  - The future of genetic and genomic medicine in health risk assessment and disease:
      a path toward individualized medicine.

PMID- 15723601
TI  - RNA interference.

PMID- 15723603
TI  - Genetic factors in aminoglycoside toxicity.
AB  - Ototoxicity is the major irreversible toxicity of aminoglycosides, and it occurs
      both in a dose-dependent and idiosyncratic fashion. The idiosyncratic pathway is
      presumably due to genetic predispositions, and an inherited mutation in the
      mitochondrial 12S ribosomal RNA gene that predisposes carriers to aminoglycoside
      ototoxicity was identified in 1993. Up to a third of patients with aminoglycoside
      ototoxicity carry this mutation. Two other mutations in the same mitochondrial
      gene affect a small minority of additional patients. Thus, the prevention of
      aminoglycoside-induced ototoxicity through family history and molecular diagnosis
      is possible in many cases. It is the challenge of genomic medicine to translate
      this more than a decade-old knowledge into clinical practice.

PMID- 15723602
TI  - Using expression information to discover new drug and vaccine targets in the
      malaria parasite Plasmodium falciparum.
AB  - The recent completion of the malaria parasite Plasmodium falciparum genome has
      opened the door for applying a variety of genomic-based systems biology
      approaches that complement existing gene-by-gene methods of investigation.
      Transcriptomic analyses of P. falciparum using DNA microarrays has allowed for
      the rapid elucidation of gene function, parasite drug response, and in vivo
      expression profiles, as well as general mechanisms guiding the parasite life
      cycle that are vital to disease pathogenesis. The results of these studies have
      identified promising novel gene targets for the development of new drug and
      vaccine therapies.

PMID- 15723604
TI  - Cytochrome P450 3A polymorphisms and immunosuppressive drugs.
AB  - With the use of powerful immunosuppressive drugs, organ transplantation has
      become the treatment of choice for many cases of end-stage chronic organ failure.
      The calcineurin inhibitors, cyclosporine and tacrolimus, which are the backbone
      of current immunosuppressive regimens, may be difficult to use because of the
      large interindividual variability of their pharmacokinetic characteristics and a
      narrow therapeutic index. Since cytochrome P450 (CYP) 3A4 and CYP3A5 are both
      involved in their metabolism, the consequences of the polymorphism of these
      enzymes were studied. It has been recently shown that the CYP3A5*3 polymorphism
      is associated with both the pharmacokinetics and pharmacodynamic consequences of
      tacrolimus. The association between the CYP3A4 and CYP3A5 polymorphisms and
      cyclosporine pharmacokinetics is more questionable. It is important to test these
      initial results prospectively to improve the individualized use of these drugs.

PMID- 15723605
TI  - Breast cancer gene expression profiling: clinical trial and practice
      implications.
AB  - The advent of high-throughput array-based technology and the sequencing of the
      human genome has provided the opportunity to begin comprehensive molecular and
      genetic profiling of cancers. Such efforts have, in a limited time, given us new
      insights into breast cancer biology and confirmed that the disease is
      considerably more heterogeneous than can be predicted by traditional
      histopathological methods. The estrogen receptor has been found to be the most
      dominant factor influencing the molecular composition of breast cancer and, in
      addition, novel subgroups of breast cancer with differing clinical outcomes have
      been observed. These may have substantial management implications for breast
      cancer patients and facilitate individualized rather than empirical oncological
      prescription. Furthermore, new methods of prognostic classification have been
      developed using array technology. The challenges ahead lie in refining the use of
      the technology, proper validation of discoveries, and the large-scale
      collaborative efforts necessary for the incorporation of genomic knowledge into
      the design and conduct of clinical trials. This will lead, ultimately, to the
      application of user-friendly tools derived from this technology to everyday
      patient care.

PMID- 15723607
TI  - Recursive partitioning analysis of complex disease pharmacogenetic studies. I.
      Motivation and overview.
AB  - Identifying genetic variation predictive of important phenotypes, including
      disease susceptibility, drug efficacy, and adverse events, is a challenging task,
      and theory and computer science work is being carried out in an attempt to tackle
      this issue. For many important diseases, such as diabetes, schizophrenia, and
      depression, the etiology is complex; either the disease is a result of several
      multiple mechanisms or is caused by an interaction among multiple genes or gene
      environment interactions, or both. There is a need for statistical methods to
      deal with the large, complex data sets that will be used to disentangle these
      diseases. Each putative genetic polymorphism can be tested for association
      sequentially. The most difficult problem, however, is the identification of
      combinations of polymorphisms or genetic markers with increased predictive
      characteristics. Data from clinical trials, where patients with a particular
      disease are treated with certain drugs, can be retrospectively assembled using a
      case-control design. Such data will typically include treatment assignment,
      demographics, medical history, and genotypes for a large number of genetic
      markers. The number of variables in such data is expected to be much larger than
      the number of subjects. This report focuses on some of the methods being employed
      to deal with this complex data and covers, in some detail, a data-mining method-
      recursive partitioning--to analyze such data. The methods are demonstrated using
      a complex simulated data set, as there are few available public data sets. This
      explication of recursive partitioning should provide researchers with a better
      idea of the current available analysis techniques, in order to allow them to plan
      their experiments more effectively.

PMID- 15723606
TI  - CEPH individuals are representative of the European American population:
      implications for pharmacogenetics.
AB  - Previous studies have highlighted the use of phenotype generation in immortalized
      lymphoblastoid cells from the Centre d'Etude du Polymorphisme Humain (CEPH)
      pedigrees as a powerful means of discovering genes involved in complex biological
      and pharmacological phenotypes. However, there is no data on how representative
      CEPH pedigrees are of the general population of European origin for genetic
      variants of pharmacogenetic significance. A vast amount of data in a population
      of restricted applicability would be of little value. Genotype and allele
      frequencies of 28 variants in 15 pharmacogenetically relevant genes were analyzed
      in germ-line DNA from European- and African-origin blood donors, and CEPH cell
      lines of European origin. The results demonstrate that allele frequencies for the
      28 polymorphisms are highly similar between the CEPH and the European-origin
      populations. However, genotype frequencies in the CEPH population did not provide
      a high level of prediction for the African-origin population. These data support
      the usefulness of the CEPH panel in pharmacogenetic discovery efforts for
      European-derived populations.

PMID- 15723608
TI  - Large recursive partitioning analysis of complex disease pharmacogenetic studies.
      II. Statistical considerations.
AB  - Identifying genetic variations predictive of important phenotypes, such as
      disease susceptibility, drug efficacy, and adverse events, remains a challenging
      task. There are individual polymorphisms that can be tested one at a time, but
      there is the more difficult problem of the identification of combinations of
      polymorphisms or even more complex interactions of genes with environmental
      factors. Diseases, drug responses or side effects can result from different
      mechanisms. Identification of subgroups of people where there is a common
      mechanism is a problem for diagnosis and prescribing of treatment. Recursive
      partitioning (RP) is a simple statistical tool for segmenting a population into
      non-overlapping groups where the response of interest, disease susceptibility,
      drug efficacy and adverse events are more homogeneous within the segments. We
      suggest that the use of RP is not only more technically feasible than other
      search methods but it is less susceptible to multiple-testing problems. The
      numbers of combinations of gene-gene and gene-environment interactions is
      potentially astronomical and RP greatly reduces the effective search and
      inference space. Moreover, the certain reliance of RP on the presence of marginal
      effects is justifiable as was found by using analytical and numerical arguments.
      In the context of haplotype analysis, results suggest that the analysis of
      individual SNPs is likely to be successful even when susceptibilities are
      determined by haplotypes. Retrospective clinical studies where cases and controls
      are collected will be a common design. This report provides methods that can be
      used to adjust the RP analysis to reflect the population incidence of the
      response of interest. Confidence limits on the incidence of the response in the
      segmented subgroups are also discussed. RP is a straightforward way to create
      realistic subgroups, and prediction intervals for the within-subgroup disease
      incidence are easily obtained.

PMID- 15723610
TI  - Treating neurodegenerative conditions through the understanding of neuronal
      apoptosis.
AB  - Neurological diseases disrupt the quality of the lives of patients and often
      leads to their premature deaths. A common feature of most neurological diseases
      is the degeneration of neurons. It is generally accepted that neuronal loss, in
      these diseases, occurs by the inappropriate activation of a cell-suicide process
      called apoptosis. Drugs that inhibit neuronal apoptosis could thus be candidates
      for therapeutic intervention in neurodegenerative disorders. In this review we
      describe advances made in recent years on the molecules and signal transduction
      pathways that regulate neuronal apoptosis either positively or negatively.
      Emphasis is on molecules that are being targeted for the potential treatment of
      neurodegenerative conditions in humans. Furthermore, we will summarize results
      from studies performed using small-molecule neuroprotective drugs that target
      specific signaling molecules known to regulate neuronal apoptosis.

PMID- 15723611
TI  - Regulation of neuronal cell death and neurodegeneration by members of the Bcl-2
      family: therapeutic implications.
AB  - The Bcl-2 family of proteins contains both anti and pro-apoptotic members that
      have been shown to regulate neuronal cell death during development and in many
      models of acute and chronic neurodegeneration. This family of proteins can be
      divided into three distinct classes based on structure and function: the anti
      apoptotic sub-group; the pro-apoptotic, multi-domain sub-group; and the pro
      apoptotic, BH3 domain-only sub-group. Alterations in the expression of Bcl-2
      family members occur in several animal and human neurodegenerative diseases
      including Alzheimer's, Huntington's and Parkinson's diseases and Amyotrophic
      Lateral Sclerosis. Similar changes are seen in in vivo and in vitro models of
      acute neurodegeneration, including stroke and traumatic brain injury. Methods to
      increase the overall expression and/or function of anti-apoptotic Bcl-2 family
      members, and thus promote neuron survival, have been studied extensively in these
      models. Most treatment efforts focus on either the targeted delivery via viral
      vectors of anti-apoptotic members of Bcl-2 family members into the affected brain
      regions of interest, the generation of direct interactions of small molecule
      inhibitors with Bcl-2 family members, or the induced expression of Bcl-2 family
      members secondary to pharmacological manipulation. Although many challenges exist
      in the design of safe and efficacious Bcl-2 family mimetics for the treatment of
      neurodegeneration, such strategies offer great promise for preserving neuron
      viability, and hopefully function, in a variety of human neurological diseases.

PMID- 15723612
TI  - Remodeling chromatin and stress resistance in the central nervous system: histone
      deacetylase inhibitors as novel and broadly effective neuroprotective agents.
AB  - Acetylation and deacetylation of histone protein plays a critical role in
      regulating gene expression in a host of biological processes including cellular
      proliferation, development, and differentiation. Accordingly, aberrant
      acetylation and deacetylation resulting from the misregulation of histone
      acetyltransferases (HATs) and/or histone deacetylases (HDACs) has been linked to
      clinical disorders such as Rubinstein-Taybi syndrome, fragile X syndrome,
      leukemia, and various cancers. Of significant import has been the development of
      small molecule HDAC inhibitors that permit pharmacological manipulation of
      histone acetylation levels and treatment of some of these diseases including
      cancer. In this Review we discuss evidence that aberrant HAT and HDAC activity
      may also be a common underlying mechanism contributing to neurodegeneration
      during acute and chronic neurological diseases, including stroke, Huntington's
      disease Amyotrophic Lateral Sclerosis and Alzheimer's disease. With this in mind,
      a number of studies examining the use of HDAC inhibitors as therapy for restoring
      histone acetylation and transcriptional activation in in vitro and in vivo
      neurodegenerative models are discussed. These studies demonstrate that
      pharmacological HDAC inhibition is a promising therapeutic approach for the
      treatment of a range of central nervous system disorders.

PMID- 15723613
TI  - Caspase function in neuronal death: delineation of the role of caspases in
      ischemia.
AB  - Cerebral ischemia is one of the major causes of morbidity and mortality in the
      Western world. Despite extensive research, adequate therapies are still elusive.
      Neuronal degeneration and death are hallmarks of stroke/ischemia. Understanding
      how the death machinery executes neuronal death in ischemia will provide
      therapeutic targets. Key to the death machinery are caspases: the family of cell
      death proteases. While much data has been published regarding caspase involvement
      in models of ischemia, the pathways have not been thoroughly defined. The
      specification of the caspases critical for death has been hampered by the use of
      non-specific reagents. Thus many conclusions about specificity are unwarranted.
      In this review we discuss how caspases can be measured and review the existing
      knowledge of the roles of specific caspases in ischemia. We also discuss
      approaches to determining the molecules that execute ischemic death.

PMID- 15723614
TI  - Targeting the JNK signaling pathway for stroke and Parkinson's diseases therapy.
AB  - The c-Jun NH2-terminal Kinase (JNK) signaling pathway is frequently induced by
      cellular stress and correlated with neuronal death. This unique property makes
      JNK signaling a promising target for developing pharmacological intervention.
      Among several neurological disorders, JNK signaling is particularly implicated in
      ischemic stroke and Parkinson's disease. The inhibitors of the JNK signaling
      pathway include upstream kinase inhibitors (for example, CEP-1347), small
      chemical inhibitors of JNK (SP600125 and AS601245), and peptide inhibitors of the
      interaction between JNK and its substrates (D-JNKI and I-JIP). The mechanisms by
      which JNK signaling induces apoptosis and evidence of cytoprotective effects of
      these JNK inhibitors are summarized in the present review.

PMID- 15723615
TI  - Mitochondria play a central role in estrogen-induced neuroprotection.
AB  - Oxidative stress, bioenergetic impairment and mitochondrial failure have all been
      implicated in the etiology of neurodegenerative diseases such as Alzheimer's
      disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), as well as
      retinal degeneration in glaucoma and retinitis pigmentosa. Moreover, at least 75
      debilitating, and often lethal, diseases are directly attributable to deletions
      or mutations in mitochondrial DNA, or in nuclear-encoded proteins destined for
      delivery to the mitochondria. Such widespread mitochondrial involvement in
      disease reflects the regulatory position mitochondrial failure plays in both
      acute necrotic cell death, and in the less catastrophic process of apoptosis. The
      potent feminizing hormone, 17 beta-estradiol (E2), has shown cytoprotective
      activities in a host of cell and animal models of stroke, myocardial infarct and
      neurodegenerative diseases. The discovery that 17alpha-estradiol, an isomer of
      E2, is equally as cytoprotective as E2 yet is >200-fold less active as a hormone,
      has permitted development of novel, more potent analogs where cytoprotection is
      independent of hormonal potency. Studies of structure-activity-relationships,
      glutathione interactions and mitochondrial function have led to a mechanistic
      model in which these steroidal phenols intercalate into cell membranes where they
      block lipid peroxidation reactions, and are in turn recycled via glutathione.
      Such a mechanism would be particularly germane in mitochondria where function is
      directly dependent on the impermeability of the inner membrane, and where
      glutathione levels are maintained at extraordinarily high 8-10mM concentrations.
      Indeed, the parental estrogens and novel analogs stabilize mitochondria under
      Ca(2+) loading otherwise sufficient to collapse membrane potential. The
      cytoprotective and mitoprotective potencies for 14 of these analogs are
      significantly correlated, suggesting that these compounds prevent cell death in
      large measure by maintaining functionally intact mitochondria. This therapeutic
      strategy is germane not only to sudden mitochondrial failure in acute
      circumstances, such as during a stroke or myocardial infarction, but also to
      gradual mitochondrial dysfunction associated with chronic degenerative disorders
      such as AD, PD and HD.

PMID- 15723616
TI  - Targeting hypoxia-inducible factor (HIF) as a therapeutic strategy for CNS
      disorders.
AB  - Hypoxia occurs when oxygen availability drops below the levels necessary to
      maintain normal rates of metabolism. Because of its high metabolic activity, the
      brain is highly sensitive to hypoxia. Severe or prolonged oxygen deprivation in
      the brain contributes to the damage associated with stroke and a variety of other
      neuronal disorders. Conversely, the extreme hypoxic environment found in the core
      of many brain tumors supports the growth of the tumor and the survival of tumor
      cells. Normal cells exposed to transient or moderate hypoxia are generally able
      to adapt to the hypoxic conditions largely through activation of the hypoxia
      inducible transcription factor HIF. HIF-regulated genes encode proteins involved
      in energy metabolism, cell survival, erythropoiesis, angiogenesis, and vasomotor
      regulation. In many instances of hypoxia or hypoxia and ischemia, the induction
      of HIF target genes may be beneficial. When these same insults occur in tissues
      that are normally poorly vascularized, such as the retina and the core of solid
      tumors, induction of the same HIF target genes can promote disease. Major new
      insights into the molecular mechanisms that regulate the oxygen-sensitivity of
      HIF, and in the development of compounds with which to manipulate HIF activity,
      are forcing serious consideration of HIF as a therapeutic target for diverse CNS
      disorders associated with hypoxia.

PMID- 15723617
TI  - Management of bladder, prostatic and pelvic floor disorders with botulinum
      neurotoxin.
AB  - Since its introduction in the late 1970s for the treatment of strabismus and
      blepharospasm, botulinum toxin (BoNT) has been increasingly used in the
      interventional treatment of several other disorders characterized by excessive or
      inappropriate muscle contractions. The use of this pluripotential agent has
      extended to a plethora of conditions including: focal dystonia; spasticity;
      inappropriate contraction in most sphincters of the body such as those associated
      with spasmodic dysphonia, esophageal achalasia, chronic anal fissure, and
      vaginismus; eye movement disorders; other hyperkinetic disorders including tics
      and tremors; autonomic disorders such as hyperhidrosis; genitourinary disorders
      such as overactive and neurogenic bladder, non-bacterial prostatitis and benign
      prostatic hyperplasia; and aesthetically undesirable hyperfunctional facial
      lines. In addition, BoNT is being investigated for the control of the pain, and
      for the management of tension or migraine headaches and myofascial pain syndrome.
      BoNT injections have several advantages over drugs and surgical therapies in the
      management of intractable or chronic disease. Systemic pharmacologic effects are
      rare; permanent destruction of tissue does not occur. Graded degrees of
      relaxation may be achieved by varying the dose injected; most adverse effects are
      transient. Finally, patient acceptance is high. In this paper, clinical
      experience over the last years with BoNT in urological impaired patients will be
      illustrated. Moreover, this paper presents current data on the use of BoNT to
      treat pelvic floor disorders.

PMID- 15723619
TI  - Novel biological agents for the treatment of hormone-refractory prostate cancer
      (HRPC).
AB  - Hormone-refractory prostate cancer (HRPC) is an inevitable evolution of prostate
      carcinogenesis, through which the normal dependence on hormones for growth and
      survival is bypassed. Although advances in terms of symptoms palliation and
      quality of life improvement have been addressed with current treatment options,
      innovative approaches are needed to improve survival rates. A thorough
      understanding of HRPC-associated molecular pathways and mechanisms of resistance
      are a prerequisite for novel potential therapeutic interventions. Preclinical and
      early clinical studies are ongoing to evaluate new therapies that target specific
      molecular entities. Agents under development include growth factor receptor
      inhibitors, small molecules targeting signal transduction pathways, apoptosis and
      cell-cycle regulators, angiogenesis and metastasis inhibitors, differentiation
      agents, telomerase inactivators, and epigenetic therapeutics. Incorporation of
      these agents into existing treatment regimens will guide us in the development of
      a multidisciplinary treatment strategy of HRPC. This article critically reviews
      published data on new biological agents that are being tested in HRPC clinical
      trials, highlights ongoing research and considers the future perspectives of this
      new class of agents.

PMID- 15723620
TI  - Chemotherapy of breast cancer in the elderly.
AB  - Breast cancer arises in about 48% of patients older than 65 years and more than
      30% occurs in those over 70 years being the leading cause of cancer-related death
      in women older than 65. Elderly patients tolerate chemotherapy poorly compared to
      their younger counterpart because of progressive reduction of organ function and
      comorbidities related to age. For this reason, the elderly have been excluded
      from or underrepresented in most cancer studies and, in clinical practice, they
      often receive inadequate and untested treatments. For adjuvant chemotherapy, a
      low percentage of patients over 70 years of age were included in few trials and
      always in a proportion much lower than the prevalence of cancer in that age
      group. Adjuvant chemotherapy, preferably including an anthracycline especially in
      patients with HER-2/neu-positive tumours, seems to be beneficial in older women
      who have substantial risk of dying of breast cancer. To date even if there is no
      specifically randomised study, single-agent chemotherapy probably might be
      considered a reasonable treatment for advanced breast cancer in the elderly. One
      of the actual main field of clinical research in the treatment of breast cancer
      is the role of targeted therapies. Chronologic age is a risk factor for
      toxicities such as myelosuppression and mucositis, and older patients may require
      more supportive care. In order to plan medical treatment in breast cancer elderly
      patients is mandatory to practice a comprehensive geriatric assessment that
      includes evaluation of comorbidities, functional dependence, socio-economic,
      emotional and cognitive conditions, an estimate of life expectancy and
      recognition of frailty. The authors review the literature regarding age-specific
      chemotherapeutic issues in the management of breast cancer elderly patients.

PMID- 15723618
TI  - Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic
      complications. Emerging new therapeutical strategies.
AB  - Macro- and microvascular disease are the most common causes of morbidity and
      mortality in patients with diabetes mellitus. Diabetic cardiovascular dysfunction
      represents a problem of great clinical importance underlying the development of
      various severe complications including retinopathy, nephropathy, neuropathy and
      increase the risk of stroke, hypertension and myocardial infarction.
      Hyperglycemic episodes, which complicate even well-controlled cases of diabetes,
      are closely associated with increased oxidative and nitrosative stress, which can
      trigger the development of diabetic complications. Hyperglycemia stimulates the
      production of advanced glycosylated end products, activates protein kinase C, and
      enhances the polyol pathway leading to increased superoxide anion formation.
      Superoxide anion interacts with nitric oxide, forming the potent cytotoxin
      peroxynitrite, which attacks various biomolecules in the vascular endothelium,
      vascular smooth muscle and myocardium, leading to cardiovascular dysfunction. The
      pathogenetic role of nitrosative stress and peroxynitrite, and downstream
      mechanisms including poly(ADP-ribose) polymerase (PARP) activation, is not
      limited to the diabetes-induced cardiovascular dysfunction, but also contributes
      to the development and progression of diabetic nephropathy, retinopathy and
      neuropathy. Accordingly, neutralization of peroxynitrite or pharmacological
      inhibition of PARP is a promising new approach in the therapy and prevention of
      diabetic complications. This review focuses on the role of nitrosative stress and
      downstream mechanisms including activation of PARP in diabetic complications and
      on novel emerging therapeutical strategies offered by neutralization of
      peroxynitrite and inhibition of PARP.

PMID- 15723621
TI  - Structure and regulation of the drug-metabolizing enzymes arylamine N
      acetyltransferases.
AB  - Arylamine N-acetyltransferases (NAT) are xenobiotic-metabolizing enzymes
      responsible for N-acetylation of many arylamines. They are also important for O
      acetylation of N-hydroxylated heterocyclic amines. These enzymes play thus an
      important role in the detoxification and activation of numerous therapeutic drugs
      and carcinogens. Two closely related polymorphic isoforms (NAT1 and NAT2) have
      been described in humans and interindividual variations in NAT genes have been
      shown to be a potential source of adverse drug reaction. In addition, NAT1 and/or
      NAT2 phenotypes may modulate the risk of certain cancers in people exposed to
      aromatic amine carcinogens. Recent advances on the regulation of human NAT1
      activity has shown that hydroxylamine and/or nitroso intermediates of NAT1
      substrates inhibit the enzyme through direct irreversible interaction with its
      catalytic cysteine residue. Oxidative molecules such as hydrogen peroxide, S
      nitrosothiols and peroxynitrite have also been shown to inactivate reversibly or
      irreversibly the enzyme in a similar manner. In this review, after summarizing
      the general background on human NAT enzymes, we focus on the recent developments
      on the regulation of the activity of these drug-metabolizing enzymes by substrate
      intermediates and by oxidant molecules. The recent findings reviewed here provide
      possible mechanisms by which these non genetic determinants inhibit NAT1 activity
      and thereby may affect drug efficacy/toxicity.

PMID- 15723622
TI  - Recent advances in pretargeted radioimmunotherapy.
AB  - Pretargeted delivery of radionuclides is based upon bispecific immunoconjugates
      that bind a target tumor antigen and a small molecule carrying the active
      payload. This strategy is supposed to combine the advantage of antibodies to
      track tumor cells in vivo and of small radiolabeled molecules that clear rapidly
      from normal organs and minimize toxicity. Many pretargeting approaches have been
      proposed, but only those using the biotin/avidin recognition system and those
      using bispecific anti-tumor x anti-hapten antibodies have been tested in the
      clinic for both immunoscintigraphy and radioimmunotherapy. Their respective
      advantages and drawbacks, as well as hurdles in the way of an effective therapy
      against solid tumors, are discussed. In the light of the encouraging results
      obtained so far in the clinic, pretargeting remains a most promising challenge
      for chemistry and biotechnology.

PMID- 15723623
TI  - Matrix metalloproteinase inhibitors: a review on pharmacophore mapping and
      (Q)SARs results.
AB  - The matrix metalloproteinases (MMPs) are a family of more than 20 enzymes that
      are intimately involved in tissue remodelling. These zinc-containing
      endopeptidases consist of several subsets of enzymes, including collagenase,
      stromelysins and gelatinases and are involved in the degradation of the
      extracellullar matrix (ECM) that forms the connective material between cells and
      around tissues. Disease processes associated with the MMPs are generally related
      to imbalance between the inhibition and activation of MMPs resulting in excessive
      degradation of the ECM. These indications include osteoarthritis rheumatoid
      arthritis, tumour metastasis and congestive heart failure. Inhibitors for these
      enzymes have been developed for the treatment of a starthingly wide array of
      disease process where matrix remodelling plays a key role. There are three major
      components to most MMP inhibitors- the zinc binding group ZBG, the peptidic
      backbone and the pocket occupying side chain. Most MMPs inhibitors are classified
      according to their ZBG. Inhibitors interactions at active-site zinc plays a
      critical role in defining the binding mode and relative inhibitor potency. The
      majority of MMP inhibitors reported in the literature contain an effective zinc
      binding group (e.g. hydroxamic acid, carboxylic acid, sulfhydryl group) that is
      either generally substituted with a peptide-like structure that mimics the
      substrates that they cleave or appended to smaller side chains that may interact
      with specific subsites (e.g., P1', P2', P3') within the active site. Although
      carboxylates exhibit weaker zinc binding properties than hydroxamates, they are
      known to show better oral bioavailability and are less prone to metabolic
      degradation. The expected loss of binding affinity after replacement of
      hydroxamates against carboxylates is faced by adequate choice of elongated S1'
      directed substituents. The need for novel selective MMP inhibitors makes them an
      attractive target for the QSAR and molecular modelling. 3-D QSAR models were
      derived using CoMFA, CoMSIA and GRID approaches leading to the identification of
      binding regions where steric, electronic or hydrophobic effects are important for
      affinity. Some structural requirements essential for achieving high binding
      affinity and selectivity are: an acidic unit tightly anchored through four
      contact points, bidentate chelation of Zn2+, carbonyl groups for hydrogen
      bonding, more than two extra units for hydrogen bonds, a hydrophobic moiety.

PMID- 15723624
TI  - NF-kappaB in human disease: current inhibitors and prospects for de novo
      structure based design of inhibitors.
AB  - Nuclear-Factor kappa B (NF-kappaB) is an inducible transcription factor of the
      Rel family, sequestered in the cytoplasm by the IkappaB family of proteins. NF
      kappaB exists in several dimeric forms, but the p50/p65 heterodimer is the
      predominant one. Activation of NF-kappaB by a range of physical, chemical, and
      biological stimuli leads to phosphorylation and proteasome dependent degradation
      of IkappaB, leading to the release of free NF-kappaB. This free NF-kappaB then
      binds to its target sites (kappaB sites in the DNA), to initiate transcription.
      This transcription has been known to be involved in a number of diseases
      including cancer, AIDS, and inflammatory disorders. The present article focuses
      on two important issues of current and future interest- firstly a review of the
      main human diseases which are initiated due to NF-kappaB mediated transcription
      is presented. Next, comprehensive information on the current inhibitors which are
      targeted to interfere with the NF-kappaB pathway is provided. This latter section
      presents a critical review on different types of latest inhibitors targeting the
      complex NF-kappaB pathway at several stages. The inhibitors developed till date
      and still under investigation, include mainly those which interfere with the
      activation of NF-kappaB. Based on the complexity of NF-kappaB activation, and the
      current knowledge of the structural biology of NF-kappaB-DNA binding, finally it
      is proposed that a better approach to inhibit NF-kappaB induced transcription
      exists. In this context, a perspective is presented in the end, proposing de novo
      design of inhibitors which directly interact with the DNA Binding region of the
      free NF-kappaB (p50 subunit), so as to generate more specific and selective leads
      of NF-kappaB-DNA binding.

PMID- 15723626
TI  - Computer-aided drug design strategies used in the discovery of fructose 1, 6
      bisphosphatase inhibitors.
AB  - Computational assessment of the binding affinity of enzyme inhibitors prior to
      synthesis is an important component of computer-aided drug design (CADD)
      paradigms. The free energy perturbation (FEP) methodology is the most accurate
      means of estimating relative binding affinities between two inhibitors. However,
      due to its complexity and computation-intensive nature, practical applications
      are restricted to analysis of structurally-related inhibitors. Accordingly, there
      is a need for methods that enable rapid assessment of a large number of
      structurally-unrelated molecules in a suitably accurate manner. In this review,
      the FEP method is compared with molecular mechanics (MM) methods to assess the
      advantages of each in the estimation of relative binding affinities of inhibitors
      to an enzyme. Qualitative predictions of relative binding free energies of
      fructose 1, 6-bisphosphatase inhibitors using MM methods are discussed and
      compared with the corresponding FEP results. The results indicate that the MM
      based methods and the FEP method are useful in the qualitative and quantitative
      assessment of relative binding affinities of enzyme inhibitors, respectively,
      prior to synthesis.

PMID- 15723627
TI  - Recent developments in the design of specific Matrix Metalloproteinase inhibitors
      aided by structural and computational studies.
AB  - It has been 10 years since a 3-dimensional structure of the catalytic domain of a
      Matrix Metalloprotease (MMP) was revealed for the first time in 1994. More than
      80 structures of different MMPs in apo and inhibited forms, determined by X-ray
      crystallography and NMR methods, have been published by the end of year 2003. A
      large number of very potent inhibitors have been disclosed in published and
      patent literature. Several MMP inhibitors entered clinical trials for the
      treatment of cancer and arthritis. Most of the first generation inhibitors have
      hydroxamic acid as the Zinc-binding group and have limited specificity. With the
      failure of these inhibitors in clinical trials, more efforts have been directed
      to the design of specific inhibitors with different Zn-binding groups in recent
      years. This review will summarize all the published structural information and
      focus on the inhibitors that were designed to take advantage of the nonprime side
      of the MMP active site using structural information and computational analysis.
      Representative structures from all MMPs are aligned to a target structure to
      provide a better understanding of the similarities and differences of the active
      site pockets. This analysis supports the view that the differences in the
      nonprime side pockets provide better opportunities for designing inhibitors with
      higher specificity. Published information on all the Zinc-binding groups of MMP
      inhibitors is reviewed for the first time. Pros and cons of inhibitors with non
      hydroxamate Zinc-binding groups in terms of specificity, toxicity and
      pharmacokinetic properties are discussed.

PMID- 15723628
TI  - Docking: successes and challenges.
AB  - The state of the art of various computational aspects of docking-based virtual
      screening of database of small molecules is presented. The review encompasses the
      different search algorithms and the scoring functions used in docking methods and
      their applications to protein and nucleic acid drug targets. Recent progress made
      in the development and application of methods to include target flexibility are
      summarized. The fundamental issues and challenges involved in comparing various
      docking methods are discussed. Limitations of current technologies as well as
      future prospects are presented.

PMID- 15723629
TI  - Discovery strategies in a BioPharmaceutical startup: maximising your chances of
      success using computational filters.
AB  - Small research-based pharmaceutical start-ups often lack the budget and do not
      have the infrastructure available to apply all possible techniques for compound
      selection. This review details our use of a range of techniques such as high
      throughput docking and similarity searching to maximize the success rate when
      attempting to identify pharmaceutically relevant ligands in a resource
      constrained environment.

PMID- 15723630
TI  - Computer-based strategy for modeling the interaction of AGRP and related peptide
      ligands with the AGRP-binding site of murine melanocortin receptors.
AB  - The hypothesis that the interaction of agouti-related protein (AGRP) and the
      melanocortin-4 receptor (MC4R) modulates feeding behavior in humans has
      stimulated the synthesis of conformationally constrained peptides, peptoids and
      small molecules in efforts to identify novel compounds that can potentially be
      used in the clinical treatment of obesity and related eating disorders. In
      addition, the availability of a high-resolution NMR structure for the MC4R
      binding domain of AGRP, and studies employing site-specific murine MC4R mutants
      have identified key intermolecular AGRP/MC4R interactions. It is therefore
      surprising that only one, relatively unsophisticated, computer-based study has
      been reported to obtain a model for the AGRP/mMC4R complex. In this review we
      outline computer-based strategies for building models of the AGRP/mMC4R and
      related peptide/mMC4R complexes, and illustrate the strengths and limitations of
      sophisticated molecular dynamics methods in obtaining information that might form
      the basis of rational efforts to discover novel drugs that selectively interact
      with melanocortin receptors.

PMID- 15723631
TI  - Antiangiogenic agents: studies on fumagillin and curcumin analogs.
AB  - Cancer is a general term used to describe many disease states, each of which are
      characterized by abnormal cell proliferation. The causes which bring about this
      abnormal cellular behavior are specific to each type of cancer. The success of
      tumor-targeted therapy is limited by this diversity. One common denominator for
      all types of cancer is the requirement of a suitable blood supply. Therefore,
      tumor vasculature has emerged as a potential target for therapeutic intervention.
      New blood vessel growth from preexisting vasculature stimulated by biochemical
      signals is termed angiogenesis. Tumor masses require a constant supply of oxygen
      and nutrients, and a means of efficient waste removal to ensure sustained
      development. Diffusion from nearby capillaries can supply adequate nutrition for
      tumors less than 2 mm in size, but for continued growth the tumors must develop
      their own blood supply. Alteration of the delicate balance of angiogenic
      stimulating factors and angiogenic inhibitors results in the phenotypic change
      from quiescence to active endothelial proliferation. To date, this angiogenic
      switch is not completely understood. The goal of antiangiogenic therapy is to
      interfere with these mechanisms and prevent tumor cells from developing a viable
      blood supply. Fumagillin is a naturally occurring antifungal agent. Curcumin is a
      natural product isolated from the spice turmeric. Both compounds have been shown
      to have antiangiogenic properties in vitro and in vivo. This paper describes
      efforts to design and prepare fumagillin and curcumin analogs and evaluate their
      corresponding antiangiogenic activities.

PMID- 15723632
TI  - The design of cationic lipids for gene delivery.
AB  - Synthetic gene delivery vectors are gaining increasing importance in gene therapy
      as an alternative to recombinant viruses. Among the various types of non-viral
      vectors, cationic lipids are especially attractive as they can be prepared with
      relative ease and extensively characterised. Further, each of their constituent
      parts can be modified, thereby facilitating the elucidation of structure-activity
      relationships. In this forward-looking review, cationic lipid-mediated gene
      delivery will mainly be discussed in terms of the structure of the three basic
      constituent parts of any cationic lipid: the polar headgroup, hydrophobic moiety
      and linker. Particular emphasis will be placed on recent advances in the field as
      well as on our own original contributions. In addition to reviewing critical
      physicochemical features (such as headgroup hydration) of monovalent lipids, the
      use of headgroups with known nucleic-acid binding modes, such as linear and
      branched polyamines, aminoglycosides and guanidinium functions, will be
      comprehensively assessed. A particularly exciting innovation in linker design is
      the incorporation of environment-sensitive groups, the intracellular hydrolysis
      of which may lead to more controlled DNA delivery. Examples of pH-, redox- and
      enzyme-sensitive functional groups integrated into the linker are highlighted and
      the benefits of such degradable vectors can be evaluated in terms of transfection
      efficiency and cationic lipid-associated cytotoxicity. Finally, possible
      correlations between the length and type of hydrophobic moiety and transfection
      efficiency will be discussed. In conclusion it may be foreseen that in order to
      be successful, the future of cationic lipid-based gene delivery will probably
      require the development of sophisticated virus-like systems, which can be viewed
      as "programmed supramolecular systems" incorporating the various functions
      required to perform in a chronological order the different steps involved in gene
      transfection.

PMID- 15723633
TI  - Thalidomide as an immunotherapeutic agent: the effects on neutrophil-mediated
      inflammation.
AB  - Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961
      because of its teratogenic effects, but has been rediscovered as an immuno
      modifying drug. It has been administered successfully for the treatment of
      erythema nodosum leprosum, aphthous ulceration in HIV disease, inflammatory bowel
      diseases, and multiple myeloma. So far, investigations into the mode of action of
      thalidomide have focused on lymphocytes and vascular endothelial cells and have
      shown that this agent inhibits the production of tumor necrosis factor (TNF)
      alpha and is an inhibitor of tumor angiogenesis. Recently, other immunological
      effects of this drug have been gaining attention, including attenuation of
      neutrophil activation and inhibition of myelo-proliferative responses. In
      autoimmune diseases, inflammation is characterized by an influx of granulocytes,
      and the association of granulocytes with gastrointestinal ulcer formation or
      rheumatic arthritis has been well documented. The suppressive effect of
      thalidomide on the activation of the nuclear transcription factor NF-(kappa)B may
      explain these effects of thalidomide. NF-(kappa)B is retained in the cytoplasm
      with I(kappa)B(alpha), and is activated by a wide variety of inflammatory stimuli
      including TNF, IL-1 and endotoxin followed by its translocation to the nucleus.
      Constitutive activation of NF-(kappa)B has been detected in various inflammatory
      diseases, while angiogenesis and organogenesis also require NF-(kappa)B
      activation. Thalidomide, on the other hand, has been shown to selectively
      suppress NF-(kappa)B activation induced by inflammatory mediators. NF-(kappa)B is
      known to be located downstream of proliferative and/or survival signaling induced
      by growth factors, which regulate anti-apoptotic genes. Myeloid cells in vitro,
      however, have been found to proceed to apoptosis as the result of the treatment
      with thalidomide and subsequent inactivation of NF-(kappa)B. These findings are
      consistent with clinical symptoms that showed the recovery from leukocytosis
      and/or neutrophilia after the administration of thalidomide. These findings shed
      new light on the anti-inflammatory properties of thalidomide and suggested that
      they may inhibit granulocyte-mediated tissue injury.

PMID- 15723634
TI  - Neurotransmitters and chemokines regulate tumor cell migration: potential for a
      new pharmacological approach to inhibit invasion and metastasis development.
AB  - The migration of tumor cells is a prerequisite for tumor cell invasion and
      metastasis development, which accounts for over 90% of cancer mortality.
      Therefore a major focus of current tumor biological research is the study of
      those factors that regulate tumor cell migration. Those chemokines and
      neurotransmitters that bind to G-protein coupled receptors (also known as
      serpentine receptors) are the most prominent of these factors. Neurotransmitters
      have been identified that have not only a stimulatory (e.g. norepinephrine)
      effect, but an inhibitory effect (e.g. GABA) as well. This is an especially
      fortuitous development, because many known agonists and antagonists of
      neurotransmitter receptors are currently being successfully used in the treatment
      of other pathological conditions (e.g. beta-blockers in the treatment of
      cardiovascular diseases). Likewise, chemokine receptor antagonists, which are
      under development for the treatment of HIV or rheumatoid arthritis, may be
      effective tools for the inhibition of chemokine-driven tumor cell migration as
      well. A further approach to inhibit tumor cell migration arises from the
      investigation of the relevant signal transduction pathways. The PKC alpha, for
      example, is a key enzyme in the regulation of tumor cell migration, but not of
      leukocyte migration. It thus offers a selective target opportunity for specific
      pharmacological agents to interfere with tumor cell migration. In this review we
      therefore summarize the current findings on those serpentine receptors involved
      in the neurotransmitter- and chemokine-regulated tumor cell migration, on the
      underlying signal transduction pathways, and on the opportunities to inhibit
      tumor cell migration and ultimately metastasis development with pharmaceutical
      agents.

PMID- 15723635
TI  - Editorial.

PMID- 15723636
TI  - The designability hypothesis and protein evolution.
AB  - The usage of protein folds in nature is known to be non-uniform: a few folds are
      used often, while most others are used relatively rarely. What makes one fold
      more successful than another? The designability explanation, which posits that
      successful folds have an exponentially larger number of compatible sequences, is
      critically reviewed, and compared with other structural and functional
      explanations. It is argued that designability is one component of fold fitness,
      but most likely not a dominant one.

PMID- 15723637
TI  - The protein folding transition state: what are Phi-values really telling us?
AB  - Protein engineering-based studies of the folding transition state have
      accelerated significantly in the last decade, and more than a half dozen proteins
      have been subjected to extensive Phi-value analysis. A general picture is
      emerging from these studies of a transition state in which the large majority of
      experimentally characterized side chains participate in relatively homogeneous
      and energetically weak interactions playing only a relatively small role in
      defining relative folding rates.

PMID- 15723638
TI  - HPr as a model protein in structure, interaction, folding and stability studies.
AB  - The small size and lack of disulphide bonds or cofactors in the Histidine
      containing phosphocarrier protein (HPr) makes it an attractive system with which
      to study structure, interaction to its enzymatic partners, and its stability and
      folding. Here we give an overview on the immense work that has been performed on
      this protein and we will show that HPr has been widely used as a model protein to
      study important aspects in modern Structural Biology.

PMID- 15723639
TI  - Millisecond protein folding studied by NMR spectroscopy.
AB  - Proteins are involved in virtually every biological process and in order to
      function, it is necessary for these polypeptide chains to fold into the unique,
      native conformation. This folding process can take place rapidly. NMR line shape
      analyses and transverse relaxation measurements allow protein folding studies on
      a microsecond-to-millisecond time scale. Together with an overview of current
      achievements within this field, we present millisecond protein folding studies by
      NMR of the cold shock protein CspB from Bacillus subtilis.

PMID- 15723640
TI  - Oxidative folding of the cystine knot motif in cyclotide proteins.
AB  - The cyclotides are a large family of plant proteins that have a cyclic backbone
      and a knotted arrangement of three conserved disulfide bonds. Despite the
      apparent complexity of their cystine knot motif it is possible to efficiently
      fold these proteins, as exemplified by oxidative folding studies on the
      prototypic cyclotide, kalata B1. This mini-review reports on the current
      understanding of the folding process in cyclotides. The synthesis and folding of
      these molecules paves the way for their application as stable molecular
      templates.

PMID- 15723641
TI  - Prosequence-mediated disulfide coupled folding of the peptide hormones guanylin
      and uroguanylin.
AB  - In contrast to their prohormones the mature peptide hormones guanylin and
      uroguanylin are not able to fold to their native disulfide connectivities upon
      oxidative folding. Structural properties of both peptide hormones and their
      precursor proteins as well as the role of their prosequences in proper disulfide
      coupled folding are reviewed. In addition, the structural behavior of a
      proguanylin mutant that closely resembles prouroguanylin has been investigated to
      gain further insight into structural properties of this homologous precursor
      protein.

PMID- 15723642
TI  - Understanding protein folding through peptide models.
AB  - From the time it was recognized that proteins are made up primarily of secondary
      structures, theories of protein folding have used secondary structural elements
      as important building blocks. Peptides have played a central role in elucidating
      the factors that stabilize individual elements of secondary structure and are now
      being employed to study higher levels of organization. The control of
      conformation in peptides has taken on new relevance with the realization that
      protein folding plays a central role in many disease states.

PMID- 15723643
TI  - How do cofactors modulate protein folding?
AB  - Cofactors are essential components of many proteins for biological activity.
      Characterization of several cofactor-binding proteins has shown that cofactors
      often have the ability to interact specifically with the unfolded polypeptides.
      This suggests that cofactor-coordination prior to polypeptide folding may be a
      relevant path in vivo. By binding before folding, the cofactor may affect both
      the mechanism and speed of folding. Here, we discuss three different cofactors
      that modulate protein-folding processes in vitro.

PMID- 15723644
TI  - Polypeptide models to understand misfolding and amyloidogenesis and their
      relevance in protein design and therapeutics.
AB  - The study of amyloid polypeptide models (polypeptides able to generate amyloid
      structures not necessarily connected with any pathology) provides an excellent
      tool to increase the understanding of the generic aspects of misfolding and
      aggregation as well as the details of the mechanism of polypeptide deposition in
      disease. This knowledge can be integrated and applied to different problems in
      therapy and biotechnology, and in particular to re-designing bio-active
      polypeptides (biopharmaceuticals) with improved properties.

PMID- 15723645
TI  - Conformations of co-translational folding intermediates.
AB  - While in vitro experiments have contributed much to our understanding of protein
      folding, we know much less about how proteins fold in the more complex
      environment of the cell. This review summarizes our current knowledge of the
      earliest in vivo folding intermediates: the conformations adopted by nascent
      polypeptides during synthesis by the ribosome. The challenges related to
      successful folding in the cellular environment, including off-pathway aggregation
      and macromolecular crowding, are also discussed.

PMID- 15723646
TI  - Modulatory effects of pH, Cu+2 and sheet breakers on aggregation of amyloid
      peptides.
AB  - The study explores in vitro by circular dichroism and mass spectrometry the
      effects of pH, Cu+2 ions and sheet-breakers on the secondary structures and self
      aggregation of beta-amyloid peptides [Abeta43, Abeta42 and Abeta40] of
      Alzheimer's disease. Within pH 5.4-7.3, more sheet structures and aggregates
      containing up to 11 peptide units were observed. Cu+2 ions led to oxidative
      degradation or aggregation depending on its concentration and time of incubation.
      beta-sheet breakers can reverse the self-aggregation process, suggesting their
      potential therapeutic use.

PMID- 15723647
TI  - Effect of metal ions and EGTA on the optical properties of concanavalin A at
      alkaline pH.
AB  - In our earlier communications, we reported the effect of salts and alcohols on
      alpha-chymotrypsinogen [1] and the existence of stable intermediates at low pH in
      bromelain [2] and glucose oxidase [3]. In the present study, the role of metal
      ions and EGTA on the conformation of concanavalin A at alkaline pH was studied by
      near- and far-UV circular dichroism, fluorescence emission spectroscopy and
      binding of a hydrophobic dye, 1-anilino-8-naphthalene sulfonate (ANS). Far-UV CD
      spectra showed the transition from an ordered secondary structure at pH 7 with a
      trough at 223 nm to a relatively unordered state at pH 12. Near-UV CD spectra
      showed the loss of signal at 290 nm, thereby indicating the disruption of native
      three dimensional structure. Maximum ANS binding occurred at pH 12 suggesting the
      presence of an intermediate or molten globule-like state at alkaline pH.

PMID- 15723648
TI  - Efficient immobilization of enzymes on microchannel surface through His-tag and
      application for microreactor.
AB  - We developed a simple immobilisation method for His-tagged enzymes on a
      microchannel surface. It facilitates immobilisation of protein molecule on
      microchannel surface through Ni-complex, using crude or purified protein
      solutions. By this method, we could immobilize proteins on microcapillary
      constantly. This method might be useful for further development of microreactor
      with reversibly immobilized enzymes.

PMID- 15723649
TI  - Throwing new light on lung cancer pathogenesis: updates on three recent topics.
AB  - Lung cancers have become the leading cause of cancer deaths in Japan, claiming
      more than 55 000 lives annually. Unfortunately, substantial improvement in terms
      of cure rates has not been achieved over the last two decades, although during
      the same period of time in-depth basic knowledge of the molecular mechanisms,
      which underlies carcinogenesis and progression of this deadly group of neoplasms,
      has accumulated at an amazing pace. It has consequently become evident that they
      have many shared but also distinct features, when comparisons are made not only
      with other common epithelial cancers of adults, such as colon cancer, but also
      within the various histologic types of lung cancers themselves. This review
      article provides an up-date on cutting-edge research into the following three
      different topics, from which important new insights have been obtained. The first
      concerns genetic instability, especially chromosome instability, and checkpoint
      failure in lung cancers. Second, we deal with EGFR mutations, which shows
      revealing specificities in various aspects. Finally, advances in the expression
      profiling analysis of both transcriptomes and proteomes of lung cancers are
      summarized.

PMID- 15723650
TI  - Beta-Catenin mutations in a mouse model of inflammation-related colon
      carcinogenesis induced by 1,2-dimethylhydrazine and dextran sodium sulfate.
AB  - In a previous study, we developed a novel mouse model for colitis-related
      carcinogenesis, utilizing a single dose of azoxymethane (AOM) followed by dextran
      sodium sulfate (DSS) in drinking water. In the present study, we investigated
      whether colonic neoplasms can be developed in mice initiated with a single
      injection of another genotoxic colonic carcinogen 1,2-dimethylhydrazine (DMH),
      instead of AOM and followed by exposure of DSS in drinking water. Male crj: CD-1
      (ICR) mice were given a single intraperitoneal administration (10, 20 or 40 mg/kg
      body weight) of DMH and 1-week oral exposure (2% in drinking water) of a non
      genotoxic carcinogen, DSS. All animals were killed at week 20, histological
      alterations and immunohistochemical expression of beta-catenin, cyclooxygenase
      (COX-2) and inducible nitric oxide synthase (iNOS) were examined in induced
      colonic epithelial lesions (colonic dysplasias and neoplasms). Also, the beta
      catenin gene mutations in paraffin-embedded colonic adenocarcinomas were analyzed
      by the single strand conformation polymorphism method, restriction enzyme
      fragment length polymorphism and direct sequencing. The incidences of colonic
      neoplasms with dysplastic lesions developed were 100% with 2.29+/-0.95
      multiplicity, and 100% with 10.38+/-4.00 multiplicity in mice given DMH at doses
      of 10 mg/kg or 20 mg/kg and 2%DSS, respectively. Although approximately half of
      the mice given DMH at a dose of 40 mg/kg bodyweight were dead after 2-3 days
      after the injection, mice who received DMH 40 mg/kg and 2%DSS had 100% incidence
      of colonic neoplasms with 9.75+/-6.29 multiplicity. Immunohistochemical
      investigation revealed that adnocarcinomas, induced by DMH at all doses and
      2%DSS, showed positive reactivities against beta-catenin, COX-2 and iNOS. In
      DMH/DSS-induced adenocarcinomas, 10 of 11 (90.9%) adenocacrcinomas had beta
      catenin gene mutations. Half of the mutations were detected at codon 37 or 41,
      encoding serine and threonine that are direct targets for phosphorylation by
      glycogen synthase kinase-3beta. The present results suggests that, as in the
      previously reported model (AOM/DSS) our experimental protocol, DMH initiation
      followed by DSS, may provide a novel and useful mouse model for investigating
      inflammation-related colon carcinogenesis and for identifying xenobiotics with
      modifying effects.

PMID- 15723651
TI  - Follicular lymphoma subgrouping by fluorescence in situ hybridization analysis.
AB  - The frequency of t(14;18) in follicular lymphoma (FL) in Japan has been reported
      to be low compared to North America and other European countries. Recently, it
      has also been reported that FL lacks t(14;18), mainly among histological grade
      3b, and occasionally has a rearranged Bcl-6 gene. It is not known whether a
      difference in histology or immunostaining pattern exists between FL with and
      without t(14;18). We performed interphase fluorescence in situ hybridization
      (FISH) analysis to detect Bcl-2/IgH, Bcl-6 gene rearrangement, Bcl-2 gene
      amplification, and the cyclinD1/IgH gene in formalin-fixed paraffin embedded
      specimens from our FL archives. The correlation between morphological features,
      histological grades, immunohistochemical findings, and cytogenetical aberrations
      was studied. In total, we found that 28 of 47 cases (59.6%) had t(14;18). Bcl-6
      gene rearrangement and extra Bcl-2 gene signals were found in five and two cases,
      respectively. Only one had cyclinD1/IgH fusion. Ten of 12 grade 1, nine of 17
      grade 2, and 0 of two grade 3 cases had fusion signals, respectively. None of the
      above abnormalities were detected in 12 of 47 cases (25.5%). Our data confirmed a
      high frequency of t(14;18) in FL in grade 1, but a lower incidence among grade 2,
      that could be attributed to the lower incidence of the translocation in FL in
      Japan. Immunostaining of both Bcl-2 and CD10 was highly predictable for the
      presence of t(14;18); the positive predictive value was 75%, suggesting the
      usefulness of the staining.

PMID- 15723652
TI  - Phytosphingosine induced mitochondria-involved apoptosis.
AB  - Sphingolipids are putative intracellular signal mediators in cell
      differentiation, growth inhibition, and apoptosis. Sphingosine, sphinganine, and
      phytosphingosine are structural analogs of sphingolipids and are classified as
      long-chain sphingoid bases. Sphingosine and sphinganine are known to play
      important roles in apoptosis. In the present study, we examined the
      phytosphingosine-induced apoptosis mechanism, focusing on mitochondria in human T
      cell lymphoma Jurkat cells. Phytosphingosine significantly induced chromatin DNA
      fragmentation, which is a hallmark of apoptosis. Enzymatic activity measurements
      of caspases revealed that caspase-3 and caspase-9 are activated in
      phytosphingosine-induced apoptosis, but there is little activation of caspase-8
      suggesting that phytosphingosine influences mitochondrial functions. In agreement
      with this hypothesis, a decrease in DeltaPsi(m) and the release of cytochrome c
      to the cytosol were observed upon phytosphingosine treatment. Furthermore,
      overexpression of mitochondria-localized anti-apoptotic protein Bcl-2 prevented
      phytosphingosine apoptotic stimuli. Western blot assays revealed that
      phytosphingosine decreases phosphorylated Akt and p70S6k. Dephosphorylation of
      Akt was partially inhibited by protein phosphatase inhibitor OA and OA attenuated
      phytosphingosine-induced apoptosis. Moreover, using a cell-free system,
      phytosphingosine directly reduced DeltaPsi(m). These results indicate that
      phytosphingosine perturbs mitochondria both directly and indirectly to induce
      apoptosis.

PMID- 15723653
TI  - Selective inhibition of cyclooxygenase-2 inhibits colon cancer cell adhesion to
      extracellular matrix by decreased expression of beta1 integrin.
AB  - High level expression of cyclooxygenase (COX)-2 is reported in 80-90% of
      colorectal adenocarcinomas. In the recent years, selective inhibitors of COX-2
      have been developed, and are shown to effectively protect against cancer
      development and progression. Colon cancer cells, as well as the epithelial cells
      in general, are dependent on appropriate interactions with the extracellular
      matrix (ECM) proteins to achieve a number of important functions, such as
      proliferation, differentiation, invasion and survival. These interactions are
      mediated via a family of cell-surface receptors called integrins, which interact
      with cytoskeletal proteins on the cytoplasmic side of the plasma membrane and
      thereby provide a link between the ECM and the cytoskeleton. In the present
      study, a high-COX-2 (high level COX-2 expression) colon cancer cell line, HT-29,
      and a low-COX-2 (low level COX-2 expression), DLD-1, were used to investigate the
      anticolon cancer effect of the selective COX-2 inhibitor, JTE-522. Moreover, to
      clarify its mechanisms of action, we focused especially on the ability to adhere
      to and to migrate on ECM. We could clearly demonstrate that, in addition to the
      decrease of the proliferative activity, JTE-522 caused a dose-dependent decrease
      in both the ability of colon cancer cells to adhere to and to migrate on ECM.
      These effects were, at least in part, dependent on the down-regulation of beta1
      integrin expression, which was evident in HT-29, the high-COX-2 colon cancer
      cells, but not the low-COX-2, DLD-1. In addition, prostaglandin E2 almost
      completely reversed the effect of JTE-522, strongly suggesting the involvement of
      a COX-2-dependent pathway. In conclusion, for the first time, we could
      demonstrate the down-regulation of beta1 integrin caused by COX-2 inhibition,
      with consequent impairment of the ability of cancer cells to adhere to and to
      migrate on ECM, which are crucial steps for cancer metastases to develop.

PMID- 15723654
TI  - Screening of DNA copy-number aberrations in gastric cancer cell lines by array
      based comparative genomic hybridization.
AB  - We performed genome-wide screening for deoxyribonucleic acid copy-number
      aberrations in 31 gastric cancer (GC) cell lines by using custom-made comparative
      genomic hybridization (CGH)-array. Copy-number gains were frequently detected at
      1q, 3q, 5p, 7p, 7q, 8q, 11q, 17q, 20p, 20q, Xp and Xq, and losses at 3p, 4p, 4q,
      8p, 9p, 18p and 18q. With respect to histological subtypes, copy-number gains at
      1p, 16p, 20p, 20q and 22q, and losses at 8p, 10p, 10q and 18q were significantly
      frequent in cell lines derived from tumors of the well-differentiated type,
      whereas copy-number gains at 1q, 7p, 7q, Xp and Xq were frequent in the
      undifferentiated type. Homozygous deletions were seen at five loci, whereas high
      level amplifications were detected in 15 of the 31 GC cell lines; these had
      occurred at 24 loci, including the segment containing CDK6 (7q21.2).
      Amplification of that gene had never been reported in GC before.
      Immunohistochemical studies showed increased levels of CDK6 protein in 54 of the
      292 primary GC samples we examined (18.5%). Cytoplasmic localization of CDK6, as
      well as CDK6 over-expression, was more frequent in well-differentiated GC than in
      undifferentiated tumors. Nuclear expression of CDK6 was more frequent in early
      stage GC than in advanced tumors, suggesting that nuclear localization of CDK6 is
      likely to be a prognostic factor for GC. Taken together, our data indicate that
      CDK6 might be involved in the pathogenesis of GC and, more generally, that CGH
      arrays have a powerful potential for identifying novel cancer-related genetic
      changes in a variety of tumors.

PMID- 15723655
TI  - Reduced expression of Dicer associated with poor prognosis in lung cancer
      patients.
AB  - Emerging evidence suggests that microRNA, which are well-conserved, abundant and
      small regulatory RNA, may be involved in the pathogenesis of human cancers. We
      recently reported that expression of let-7 was frequently reduced in lung
      cancers, and that reduced let-7 expression was significantly associated with
      shorter patient survival. Two members of the double-stranded RNA-specific
      endonuclease family, Dicer and Drosha, convert precursor forms of microRNA into
      their mature forms using a stepwise process. In the present study, we examined
      expression levels of these genes in 67 non-small cell lung cancer cases, and
      found for the first time that Dicer expression levels were reduced in a fraction
      of lung cancers with a significant prognostic impact on the survival of
      surgically treated cases. It should be noted that multivariate COX regression
      analysis showed that the prognostic impact of Dicer (P=0.001) appears to be
      independent of disease stage (P=0.001), while logistic regression analysis
      demonstrated that the higher incidence of reduced Dicer expression in poorly
      differentiated tumors remained significant even after correction for other
      parameters (P=0.02). Given the fundamental and multiple biological roles of Dicer
      in various cellular processes, our results suggest the involvement of reduced
      Dicer expression in the development of lung cancers, thus warranting further
      investigations of the underlying mechanisms, which can be expected to enhance
      understanding of the molecular pathogenesis of this fatal cancer.

PMID- 15723656
TI  - STI571 (Glivec) inhibits the interaction between c-KIT and heat shock protein 90
      of the gastrointestinal stromal tumor cell line, GIST-T1.
AB  - The gastrointestinal stromal tumor cell line, GIST-T1, has a heterogenic 57-base
      pair deletion in exon 11 of the c-kit mutation, and the c-KIT protein in the GIST
      T1 cells constitutively activated. We report that STI571 (Glivec; Novartis,
      Basel, Switzerland), a specific inhibitor of c-KIT, inhibits the clustering of c
      KIT at the cell membrane of the GIST-T1 cells. Furthermore, STI571 prevents the
      interaction between c-KIT and the molecular chaperone, heat shock protein 90
      (Hsp90). Geldanamycin, an inhibitor of Hsp90, also prevents interaction between c
      KIT and Hsp90, and inhibits tyrosine phosphorylation of c-KIT. Our results
      indicate that c-KIT molecules are assembled on the cell surface of the GIST-T1
      cells, and that the interaction between c-KIT and Hsp90 plays an important role
      in c-KIT activation.

PMID- 15723657
TI  - Lung cancer death rates by smoking status: comparison of the Three-Prefecture
      Cohort study in Japan to the Cancer Prevention Study II in the USA.
AB  - Cigarette smoking is an established risk factor for lung cancer. However, the
      magnitude of the relative risk (RR) on lung cancer mortality in relation to
      cigarette smoking is reported to be lower in Japan than in Western countries. We
      investigated whether this discrepancy could be explained by differences in the
      exposure to cigarettes smoked, by differences in sensitivity to smoking, or by
      differences in lung cancer mortality among non-smokers. We examined the 10-year
      follow-up data on 88,153 participants in a Japanese population-based prospective
      study conducted in three prefectures. Data used as a Western counterpart was
      retrieved from a published report of the US Cancer Prevention Study (CPS)-II.
      Although there was a significant increased risk of lung cancer death among
      current smokers compared with non-smokers, the observed RR in the Three
      Prefecture Study were much lower than RR reported in the CPS-II. Lung cancer
      mortality of our Japanese sample was lower among current smokers and higher among
      non-smokers regardless of age and sex. Current smokers in our sample had
      initiated smoking at an older age and smoked fewer cigarettes per day for shorter
      durations than those in the CPS-II sample. The Poisson regression model
      (controlling for age, number of cigarettes smoked per day and duration of
      smoking) showed that male current smokers in our sample had a lower risk of lung
      cancer compared with those in the CPS-II sample (rate ratio 0.34 [95%CI 0.27
      0.43]). These findings might explain why Japanese risks of lung cancer are lower
      than those observed in Western countries.

PMID- 15723658
TI  - Activated human umbilical cord blood dendritic cells kill tumor cells without
      damaging normal hematological progenitor cells.
AB  - Apart from their role as antigen presenting cells, human peripheral blood
      monocyte and CD34+ cell-derived dendritic cells (DC), have been demonstrated to
      exert cytotoxicity against some tumor cells, and their tumoricidal activity can
      be enhanced by some stimili. However, there have been no reports concerning the
      tumoricidal activity of human cord blood dendritic cells (CBDC). In this article,
      we report that human cord blood monocyte-derived DC acquire the ability to kill
      hematological tumor cells, after activation with lipopolysaccharide (LPS) or
      gamma-interferon (IFN-gamma), associated with the enhanced TNF-alpha-related
      apoptosis-inducing ligand (TRAIL) expression in CBDC cytoplasm. The CD14-positive
      cells collected from cord blood were induced to CBDC in vitro. After activation
      with IFN-gamma for 12 h, CBDC exhibited cytotoxicity against HL60 and Jurkat
      cells, while activation with LPS induced cytotoxicity against Daudi and Jurkat
      cells. However, both LPS- and IFN-gamma-stimulated CBDC showed no cytotoxic
      activity against normal CD14-negative cord blood mononuclear cells. The formation
      of umbilical cord hematopoietic progenitor colonies, identified as burst-forming
      unit-erythroid and colony-forming unit granulocyte-macrophage, was not inhibited
      by stimulated or unstimulated CBDC. IFN-gamma or LPS stimulation enhanced
      intracellular but not cellular surface TRAIL, and neither intracellular nor
      cellular surface tumor necrosing factor-alpha and Fas Ligand as analyzed by flow
      cytometry. Our results show that activated CBDC can serve as cytotoxic cells
      against hematological tumor cells without damaging the normal hematopoietic
      progenitor cells.

PMID- 15723659
TI  - Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in response to
      DNA damage.
AB  - Artemis plays a crucial role in the hairpin-opening step of antigen receptor VDJ
      gene recombination in the presence of catalytic subunit of deoxyribonucleic acid
      (DNA)-dependent protein kinase (DNA-PKcs). A defect in Artemis causes human
      radiosensitive-severe combined immunodeficiency. Cells from Artemis-deficient
      patients and mice display increased chromosomal instability, but the precise
      function of this factor in the response to DNA damage remains to be elucidate. In
      this study, we show that Artemis is hyperphosphorylated in an Ataxia
      telangiectasia-mutated (ATM)- and Nijmegen breakage syndrome 1 (Nbs1)-dependent
      manner in response to ionizing radiation (IR), and that S645 is an SQ/TQ site
      that contributes to retarded mobility of Artemis upon IR. The
      hyperphosphorylation of Artemis is markedly reduced in ATM- and Nbs1-null cells.
      Reintroduction of wild-type ATM or Nbs1 reconstituted Artemis
      hyperphosphorylation in ATM- or Nbs1-deficient cells, respectively. In support of
      this functional link, hyperphosphorylated Artemis was found to physically
      associate with the Mre11/Rad50/Nbs1 complex in an ATM-dependent manner in
      response to IR-induced DNA double strand breaks (DSB). Since deficiency of either
      DNA-Pkcs or ATM leads to defective repair of IR-induced DSB, our finding places
      Artemis at the signaling crossroads downstream of DNA-PKcs and ATM in IR-induced
      DSB repair.

PMID- 15723660
TI  - Using genome scans of DNA polymorphism to infer adaptive population divergence.
AB  - Elucidating the genetic basis of adaptive population divergence is a goal of
      central importance in evolutionary biology. In principle, it should be possible
      to identify chromosomal regions involved in adaptive divergence by screening
      genome-wide patterns of DNA polymorphism to detect the locus-specific signature
      of positive directional selection. In the case of spatially separated populations
      that inhabit different environments or sympatric populations that exploit
      different ecological niches, it is possible to identify loci that underlie
      divergently selected traits by comparing relative levels of differentiation among
      large numbers of unlinked markers. In this review I first address the question of
      whether diversifying selection on polygenic traits can be expected to produce
      predictable patterns of allelic variation at the underlying quantitative trait
      loci (QTL), and whether the locus-specific effects of selection can be reliably
      detected against the genome-wide backdrop of stochastic variability. I then
      review different approaches that have been developed to identify loci involved in
      adaptive population divergence and I discuss the relative merits of model-based
      approaches that rely on assumptions about population structure vs. model-free
      approaches that are based on empirical distributions of summary statistics.
      Finally, I consider the evolutionary and functional insights that might be gained
      by conducting genome scans for loci involved in adaptive population divergence.

PMID- 15723662
TI  - Mutation at high rates reduces spatial structure within populations.
AB  - The question of whether or not the high rates (mu) of mutation that occur for
      some hypervariable markers can affect commonly used empirical measures of spatial
      structure of genetic variation within populations is addressed. The results show
      that values of these measures are approximately halved when mu is 10(-2). Finest
      spatial-scale correlations, measured by either Moran's I-statistics or
      conditional kinship, are reduced by 30%-50%. When the mutation rate is 10 times
      lower, much smaller reductions result, e.g. averaging 7% for the finest scale
      correlations. Still smaller orders of magnitude of mu cause negligible changes in
      spatial structure, where any effects normally would not be detectable. The
      reductions are caused by forward mutations, and when the reductions are measured
      as percentages, they are nearly independent of the amount of structure produced
      sans mutation, except when dispersal is nearly minimal. The percent reductions
      are also nearly independent of the number of alleles and of back mutations, hence
      of the nature of the mutation process (e.g. stepwise or not). The results
      demonstrate that some hypervariable loci should have reduced spatial structuring,
      and that marker choice may affect the values observed in experimental surveys.
      Moreover, if fine-scale correlations are used to indirectly estimate dispersal
      distances, then mutation at high rates could inflate estimates, easily up to two-
      to three-fold.

PMID- 15723661
TI  - Comparative organization of chloroplast, mitochondrial and nuclear diversity in
      plant populations.
AB  - Plants offer excellent models to investigate how gene flow shapes the
      organization of genetic diversity. Their three genomes can have different modes
      of transmission and will hence experience varying levels of gene flow. We have
      compiled studies of genetic structure based on chloroplast DNA (cpDNA),
      mitochondrial DNA (mtDNA) and nuclear markers in seed plants. Based on a data set
      of 183 species belonging to 103 genera and 52 families, we show that the
      precision of estimates of genetic differentiation (G(ST)) used to infer gene flow
      is mostly constrained by the sampling of populations. Mode of inheritance appears
      to have a major effect on G(ST). Maternally inherited genomes experience
      considerably more subdivision (median value of 0.67) than paternally or
      biparentally inherited genomes (approximately 0.10). G(ST) at cpDNA and mtDNA
      markers covary narrowly when both genomes are maternally inherited, whereas G(ST)
      at paternally and biparentally inherited markers also covary positively but more
      loosely and G(ST) at maternally inherited markers are largely independent of
      values based on nuclear markers. A model-based gross estimate suggests that, at
      the rangewide scale, historical levels of pollen flow are generally at least an
      order of magnitude larger than levels of seed flow (median of the pollen-to-seed
      migration ratio: 17) and that pollen and seed gene flow vary independently across
      species. Finally, we show that measures of subdivision that take into account the
      degree of similarity between haplotypes (N(ST) or R(ST)) make better use of the
      information inherent in haplotype data than standard measures based on allele
      frequencies only.

PMID- 15723663
TI  - Population genetic structure of annual and perennial populations of Zostera
      marina L. along the Pacific coast of Baja California and the Gulf of California.
AB  - The Baja California peninsula represents a biogeographical boundary contributing
      to regional differentiation among populations of marine animals. We investigated
      the genetic characteristics of perennial and annual populations of the marine
      angiosperm, Zostera marina, along the Pacific coast of Baja California and in the
      Gulf of California, respectively. Populations of Z. marina from five coastal
      lagoons along the Pacific coast and four sites in the Gulf of California were
      studied using nine microsatellite loci. Analyses of variance revealed significant
      interregional differentiation, but no subregional differentiation. Significant
      spatial differentiation, assessed using theta(ST) values, was observed among all
      populations within the two regions. Z. marina populations along the Pacific coast
      are separated by more than 220 km and had the greatest theta(ST) (0.13-0.28)
      values, suggesting restricted gene flow. In contrast, lower but still significant
      genetic differentiation was observed among populations within the Gulf of
      California (theta(ST) = 0.04-0.18), even though populations are separated by more
      than 250 km. This suggests higher levels of gene flow among Gulf of California
      populations relative to Pacific coast populations. Direction of gene flow was
      predominantly southward among Pacific coast populations, whereas no dominant
      polarity in the Gulf of California populations was observed. The test for
      isolation by distance (IBD) showed a significant correlation between genetic and
      geographical distances in Gulf of California populations, but not in Pacific
      coast populations, perhaps because of shifts in currents during El Nino Southern
      Oscillation (ENSO) events along the Pacific coast.

PMID- 15723664
TI  - Population genetics of the diamondback terrapin (Malaclemys terrapin).
AB  - We examined the population genetic structure of the diamondback terrapins
      (Malaclemys terrapin), within and among estuaries. Based on mark-recapture
      studies, these estuarine turtles have high site fidelity that is likely to make
      them vulnerable to local extinctions. We tested if observed site fidelity of
      adults would be reflected in intraestuarine population genetic structure of six
      highly polymorphic microsatellite loci (five tetranucleotide and one
      dinucleotide). No evidence was found for population structuring within the
      Charleston estuary nor among three different estuaries in South Carolina. We then
      examined four other terrapin populations from North Carolina to New York, as well
      as from the Florida Keys and from Texas. With increasing geographical distance,
      genetic differentiation increased from South Carolina through New York, but
      overall values were low. The dinucleotide locus contributed significantly more to
      the genetic differentiation of some population comparisons than any of the other
      loci. Interestingly, terrapins from South Carolina to New York were much more
      genetically similar to those from Texas (rho = 0.154) than to those from Florida
      (rho = 0.357). We attribute this pattern to extensive translocations of terrapins
      during the early 20th century to replenish diminished populations and to provide
      turtle farms with stocks. Terrapins collected in Texas were especially sought for
      shipment to the northeastern US because of their larger size. Our study indicates
      no population structure within or among adjacent estuaries. Thus, the mark
      recapture information from adult and subadult feeding locations is a poor
      predictor of population genetic structure. Additionally, it appears that past
      human activities may have drastically altered the genetics of current
      populations. Finally, our data suggest that translocation of eggs or head
      starting of terrapins within estuaries or among adjacent estuaries is acceptable
      from a genetic standpoint.

PMID- 15723665
TI  - Genetic changes associated to declining populations of Formica ants in fragmented
      forest landscape.
AB  - We monitored populations of two wood ant species, Formica aquilonia and Formica
      lugubris, through annual mapping of the colonies in a fragmenting forest
      landscape from 1966 to 1998. The genetic population structure was studied at the
      end of the study period by using 12 microsatellite loci. Fragmentation of forest
      led to a decline and spatial redistribution of populations. Changes in the
      spatial distribution were particularly pronounced in the highly polygynous (many
      queens in a single nest) species F. aquilonia, whose local populations declined
      or became extinct, or relocated themselves and colonized new patches. The genetic
      relationships of the remaining subpopulations indicated the historical
      developments, revealing the boundaries of the historical populations (high values
      of genetic differentiation, F(ST)), recolonization histories (genetic affinities
      revealed by Bayesian analyses) and population decline (reduced variation). Big
      genetic differences could be detected over short distances, so differentiation
      also depended on social factors. Our results showed that a genetic study can be
      reliably used to dissect the recent historical changes underlying the present
      population structure, and that species with different social structures can
      respond differently to habitat changes. Combining our demographic and genetic
      results suggests that habitat fragmentation forms a clear threat on a local scale
      with large negative effects on ant population viability.

PMID- 15723666
TI  - Clonal diversity and population genetic structure of arbuscular mycorrhizal fungi
      (Glomus spp.) studied by multilocus genotyping of single spores.
AB  - A nested multiplex PCR (polymerase chain reaction) approach was used for
      multilocus genotyping of arbuscular mycorrhizal fungal populations. This method
      allowed us to amplify multiple loci from Glomus single spores in a single PCR
      amplification. Variable introns in the two protein coding genes GmFOX2 and GmTOR2
      were applied as codominant genetic markers together with the LSU rDNA. Genetic
      structure of Glomus spp. populations from an organically and a conventionally
      cultured field were compared by hierarchical sampling of spores from four plots
      in each field. Multilocus genotypes were characterized by SSCP (single stranded
      conformation polymorphism) and sequencing. All spore genotypes were unique
      suggesting that no recombination was taking place in the populations. There were
      no overall differences in the distribution of genotypes in the two fields and
      identical genotypes could be sampled from both fields. Analysis of gene diversity
      indicated that Glomus populations are subdivided between plots within each field.
      There were however, no subdivision between the fields.

PMID- 15723667
TI  - Phylogeography of Daphnia magna in Europe.
AB  - The phylogeographical structure of the water flea Daphnia magna in Europe was
      analysed using a 609-bp fragment of the cytochrome oxidase subunit I gene. Only
      moderate overall genetic divergence was detected within Europe. We detected four
      genetically and, to a large extent, geographically distinct phylogroups within
      Europe. Our results suggest that these groups recolonized large parts of Europe
      around 100,000 BP from different refugia. Overall, the pattern suggests a high
      degree of provincialism with a patchy occurrence of specific lineages, thus
      confirming the highly subdivided genetic structure usually observed in freshwater
      zooplankton populations. Although the region around the Mediterranean Sea was
      only sampled patchily, we obtained strong indications for the occurrence of more
      divergent genetic lineages in this region. Comparing our European samples to
      samples from North America and Japan revealed a higher level of differentiation,
      reflecting limited intercontinental dispersal.

PMID- 15723668
TI  - Phylogeography of a nematode (Heligmosomoides polygyrus) in the western
      Palearctic region: persistence of northern cryptic populations during ice ages?
AB  - This study establishes the continental phylogeographical pattern of a European
      nematode, Heligmosomoides polygyrus (Dujardin, 1845; Heligmosomoidea). We
      sequenced 687 base pairs of the mitochondrial DNA (mtDNA) cyt b gene for 136
      individuals collected in 22 localities. The results revealed that H. polygyrus
      populations are separated into five major units corresponding to the Italian,
      northern European (Denmark and Ireland), Iberian, western European, and Balkan
      populations. Different subclades were also observed within the first two groups.
      Based on the rate of molecular evolution of H. polygyrus cyt b gene-estimated to
      3.5%-3.7% divergence per million years (Myr) in a previous study--the isolation
      time of the five clades was estimated between 2.5 +/- 0.24 and 1.5 +/- 0.23
      million years ago. Moreover, H. polygyrus presents a higher genetic variability
      in the Mediterranean peninsulas as compared to northwestern Europe, highlighting
      the role of these regions as refuge areas. Like its specific host, the wood mouse
      Apodemus sylvaticus, H. polygyrus' pattern of postglacial recolonization of
      northwestern Europe was initiated from Iberian populations, while Italian and
      Balkan populations did not expand to the north. The results also suggest the
      existence of forested and temperate refuges in the southern British Isles during
      the Quaternary. Finally, the genetic diversity as well as the level of genetic
      divergence between the lineages of H. polygyrus are compared to those observed in
      other vertebrate and invertebrate phylogeographical studies: the existence of
      highly differentiated lineages in H. polygyrus (5%-10% of genetic divergence)
      highlights that the effects of Pleistocene climate changes on free-living
      organisms are also reflected in their obligate parasites.

PMID- 15723669
TI  - Cytoplasmic and nuclear markers reveal contrasting patterns of spatial genetic
      structure in a natural Ipomopsis hybrid zone.
AB  - Spatial variation in natural selection may play an important role in determining
      the genetic structure of hybridizing populations. Previous studies have found
      that F1 hybrids between naturally hybridizing Ipomopsis aggregata and Ipomopsis
      tenuituba in central Colorado differ in fitness depending on both genotype and
      environment: hybrids had higher survival when I. aggregata was the maternal
      parent, except in the centre of the hybrid zone where both hybrid types had high
      survival. Here, we developed both maternally (cpDNA PCR-RFLP) and biparentally
      inherited (nuclear AFLP) species-diagnostic markers to characterize the spatial
      genetic structure of the natural Ipomopsis hybrid zone, and tested the prediction
      that the majority of natural hybrids have I. aggregata cytoplasm, except in areas
      near the centre of the hybrid zone. Analyses of 352 individuals from across the
      hybrid zone indicate that cytoplasmic gene flow is bidirectional, but contrary to
      expectation, most plants in the hybrid zone have I. tenuituba cytoplasm. This
      cytotype distribution is consistent with a hybrid zone in historical transition,
      with I. aggregata nuclear genes advancing into the contact zone. Further, nuclear
      data show a much more gradual cline than cpDNA markers that is consistent with
      morphological patterns across the hybrid populations. A mixture of environment-
      and pollinator-mediated selection may contribute to the current genetic structure
      of this hybrid system.

PMID- 15723670
TI  - Phylogeographic analysis of the red seaweed Palmaria palmata reveals a
      Pleistocene marine glacial refugium in the English Channel.
AB  - Phylogeography has provided a new approach to the analysis of the postglacial
      history of a wide range of taxa but, to date, little is known about the effect of
      glacial periods on the marine biota of Europe. We have utilized a combination of
      nuclear, plastid and mitochondrial genetic markers to study the biogeographic
      history of the red seaweed Palmaria palmata in the North Atlantic. Analysis of
      the nuclear rDNA operon (ITS1-5.8S-ITS2), the plastid 16S-trnI-trnA-23S-5S, rbcL
      rbcS and rpl12-rps31-rpl9 regions and the mitochondrial cox2-3 spacer has
      revealed the existence of a previously unidentified marine refugium in the
      English Channel, along with possible secondary refugia off the southwest coast of
      Ireland and in northeast North America and/or Iceland. Coalescent and mismatch
      analyses date the expansion of European populations from approximately 128,000 BP
      and suggest a continued period of exponential growth since then. Consequently, we
      postulate that the penultimate (Saale) glacial maximum was the main event in
      shaping the biogeographic history of European P. palmata populations which
      persisted throughout the last (Weichselian) glacial maximum (c. 20,000 BP) in the
      Hurd Deep, an enigmatic trench in the English Channel.

PMID- 15723671
TI  - Multiple paternity and postcopulatory sexual selection in a hermaphrodite: what
      influences sperm precedence in the garden snail Helix aspersa?
AB  - Sperm competition has been studied in many gonochoric animals but little is known
      about its occurrence in simultaneous hermaphrodites, especially in land snails.
      The reproductive behaviour of the land snail Helix aspersa involves several
      features, like multiple mating, long-term sperm storage and dart-shooting
      behaviour, which may promote sperm competition. Cryptic female choice may also
      occur through a spermatheca subdivided into tubules, which potentially allows
      compartmentalized sperm storage of successive mates. In order to determine the
      outcome of postcopulatory sexual selection in this species, we designed a cross
      breeding experiment where a recipient ('female') mated with two sperm donors
      ('males'). Mates came from either the same population as the recipient or from a
      distinct one. To test for the influence a recipient can have on the paternity of
      its offspring, we excluded the effects of dart shooting by using only virgin
      snails as sperm donors because they do not shoot any dart before their first
      copulation. We measured the effects of size of mates as well as time to first and
      second mating on second mate sperm precedence (P2; established using
      microsatellite markers). Multiple paternity was detected in 62.5% of clutches and
      overall there was first-mate sperm precedence with a mean P2 of 0.24. Generalized
      linear modelling revealed that the best predictors of paternity were the time
      between matings and the time before first mating. Overall, both first and second
      mates that copulated quickly got greater parentage, which may suggest that
      postcopulatory events influence patterns of sperm precedence in the garden snail.

PMID- 15723672
TI  - Task-specific expression of the foraging gene in harvester ants.
AB  - In social insects, groups of workers perform various tasks such as brood care and
      foraging. Transitions in workers from one task to another are important in the
      organization and ecological success of colonies. Regulation of genetic pathways
      can lead to plasticity in social insect task behaviour. The colony organization
      of advanced eusocial insects evolved independently in ants, bees, and wasps and
      it is not known whether the genetic mechanisms that influence behavioural
      plasticity are conserved across species. Here we show that a gene associated with
      foraging behaviour is conserved across social insect species, but the expression
      patterns of this gene are not. We cloned the red harvester ant (Pogonomyrmex
      barbatus) ortholog (Pbfor) to foraging, one of few genes implicated in social
      organization, and found that foraging behaviour in harvester ants is associated
      with the expression of this gene; young (callow) worker brains have significantly
      higher levels of Pbfor mRNA than foragers. Levels of Pbfor mRNA in other worker
      task groups vary among harvester ant colonies. However, foragers always have the
      lowest expression levels compared to other task groups. The association between
      foraging behaviour and the foraging gene is conserved across social insects but
      ants and bees have an inverse relationship between foraging expression and
      behaviour.

PMID- 15723673
TI  - Rapid screening of invertebrate predators for multiple prey DNA targets.
AB  - DNA-based techniques are providing valuable new approaches to tracking predator
      prey interactions. The gut contents of invertebrate predators can be analysed
      using species-specific primers to amplify prey DNA to confirm trophic links. The
      problem is that each predator needs to be analysed with primers for the tens of
      potential prey available at a field site, even though the mean number of species
      detected in each gut may be as few as one or two. Conducting all these PCRs
      (polymerase chain reactions) is a lengthy process, and effectively precludes the
      analysis of the hundreds of predators that might be required for a meaningful
      ecological study. We report a rapid, more sensitive and practical approach.
      Multiplex PCRs, incorporating fluorescent markers, were found to be effective at
      amplifying degraded DNA from predators' guts and could amplify mitochondrial DNA
      fragments from 10+ species simultaneously without 'drop outs'. The combined PCR
      products were then separated by size on polyacrylamide gels on an ABI377
      sequencer. New primers to detect the remains of aphids, earthworms, weevils and
      molluscs in the guts of carabid predators were developed and characterized. The
      multiplex-sequencer approach was then applied to field-caught beetles, some of
      which contained DNA from as many as four different prey at once. The main prey
      detected in the beetles proved to be earthworms and molluscs, although aphids and
      weevils were also consumed. The potential of this system for use in food-web
      research is discussed.

PMID- 15723674
TI  - Hyperdiversity of ectomycorrhizal fungus assemblages on oak seedlings in mixed
      forests in the southern Appalachian Mountains.
AB  - Diversity of ectotrophic mycobionts on outplanted seedlings of two oak species
      (Quercus rubra and Quercus prinus) was estimated at two sites in mature mixed
      forests in the southern Appalachian Mountains by sequencing nuclear 5.8S rRNA
      genes and the flanking internal transcribed spacer regions I and II (ITS). The
      seedlings captured a high diversity of mycorrhizal ITS-types and late-stage fungi
      were well represented. Total richness was 75 types, with 42 types having a
      frequency of only one. The first and second order jackknife estimates were 116
      and 143 types, respectively. Among Basidiomycetes, tomentelloid/thelephoroid,
      russuloid, and cortinarioid groups were the richest. The ascomycete Cenococcum
      geophilum was ubiquitously present. Dominant fungi included a putative Tuber sp.
      (Ascomycetes), and Basidiomycetes including a putative Craterellus sp., and
      Laccaria cf. laccata. Diversity was lower at a drier high elevation oak forest
      site compared to a low elevation mesic cove--hardwood forest site. Fungal
      specificity for red oak vs. white oak seedlings was unresolved. The high degree
      of rarity in this system imposes limitations on the power of community analyses
      at finer scales. The high mycobiont diversity highlights the potential for
      seedlings to acquire carbon from mycelial networks and confirms the utility of
      using outplanted seedlings to estimate ectomycorrhizal diversity.

PMID- 15723675
TI  - An insight into the genetic variation of Schistosoma japonicum in mainland China
      using DNA microsatellite markers.
AB  - This study presents the first microsatellite investigation into the level of
      genetic variation among Schistosoma japonicum from different geographical
      origins. S. japonicum isolates were obtained from seven endemic provinces across
      mainland China: Zhejiang (Jiashan County), Anhui (Guichi County), Jiangxi
      (Yongxiu County), Hubei (Wuhan County), Hunan (Yueyang area), Sichuan 1 (Maoshan
      County), Sichuan 2 (Tianquan County), Yunnan (Dali County), and also one province
      in the Philippines (Sorsogon). DNA from 20 individuals from each origin were
      screened against 11 recently isolated and characterized S. japonicum
      microsatellites, and a set of nine loci were selected based on their polymorphic
      information content. High levels of polymorphism were obtained between and within
      population samples, with Chinese and Philippine strains appearing to follow
      different lineages, and with distinct branching between provinces. Moreover,
      across mainland China, genotype clustering appeared to be related to habitat type
      and/or intermediate host morph. These results highlight the suitability of
      microsatellites for population genetic studies of S. japonicum and suggest that
      there may be different strains of S. japonicum circulating in mainland China.

PMID- 15723676
TI  - The latitudinal cline in the In(3R)Payne inversion polymorphism has shifted in
      the last 20 years in Australian Drosophila melanogaster populations.
AB  - Clinal variation has been described in a number of inversions in Drosophila but
      these clines are often characterized by cytological techniques using small sample
      sizes, and associations with specific genes are rarely considered. Here we have
      developed a molecular assay for In(3R)Payne in Drosophila melanogaster from
      eastern Australia populations. It shows in repeated samples that the inversion
      cline is very tightly associated with latitude and is almost fixed in tropical
      populations while relatively rare in temperate populations. This steep cline has
      shifted in position in the last 20 years. The heat shock gene, hsr-omega, located
      centrally inside the inversion sequence, shows a different clinal pattern to
      In(3R)Payne. These results suggest strong ongoing selection on In(3R)Payne over
      the last 100 years since the colonization of Australia that is partly independent
      of hsr-omega.

PMID- 15723677
TI  - Phenotypic divergence despite high levels of gene flow in Galapagos lava lizards
      (Microlophus albemarlensis).
AB  - The extent of evolutionary divergence of phenotypes between habitats is
      predominantly the result of the balance of differential natural selection and
      gene flow. Lava lizards (Microlophus albemarlensis) on the small island of Plaza
      Sur in the Galapagos archipelago inhabit contrasting habitats: dense vegetation
      on the western end of the island thins rapidly in a transitional area, before
      becoming absent on the eastern half. Associated with these habitats are
      phenotypic differences in traits linked to predator avoidance (increased
      wariness, sprint speed, and endurance in lizards from the sparsely vegetated
      habitat). This population provides an opportunity to test the hypothesis that
      reduced gene flow is necessary for phenotypic differentiation. There was no
      evidence of any differences among habitats in allele frequencies at six out of
      seven microsatellite loci examined, nor was there any indication of congruence
      between patterns of genetic variability and the change in vegetation regime. We
      infer that gene flow between the habitats on Plaza Sur must be sufficiently high
      to overcome genetic drift within habitats but that it does not preclude
      phenotypic differentiation.

PMID- 15723678
TI  - Is genome size influenced by colonization of new environments in dipteran
      species?
AB  - Genome size differences are usually attributed to the amplification and deletion
      of various repeated DNA sequences, including transposable elements (TEs). Because
      environmental changes may promote modifications in the amount of these repeated
      sequences, it has been postulated that when a species colonizes new environments
      this could be followed by an increase in its genome size. We tested this
      hypothesis by estimating the genome size of geographically distinct populations
      of Drosophila ananassae, Drosophila malerkotliana, Drosophila melanogaster,
      Drosophila simulans, Drosophila subobscura, and Zaprionus indianus, all of which
      have known colonization capacities. There was no strong statistical differences
      between continents for most species. However, we found that populations of D.
      melanogaster from east Africa have smaller genomes than more recent populations.
      For species in which colonization is a recent event, the differences between
      genome sizes do not thus seem to be related to colonization history. These
      findings suggest either that genome size is seldom modified in a significant way
      during colonization or that it takes time for genome size of invading species to
      change significantly.

PMID- 15723679
TI  - TaqMan DNA technology confirms likely overestimation of cod (Gadus morhua L.) egg
      abundance in the Irish Sea: implications for the assessment of the cod stock and
      mapping of spawning areas using egg-based methods.
AB  - Recent substantial declines in northeastern Atlantic cod stocks necessitate
      improved biological knowledge and the development of techniques to complement
      standard stock assessment methods (which largely depend on accurate commercial
      catch data). In 2003, an ichthyoplankton survey was undertaken in the Irish Sea
      and subsamples of 'cod-like' eggs were analysed using a TaqMan multiplex, PCR
      (polymerase chain reaction) assay (with specific probes for cod, haddock and
      whiting). The TaqMan method was readily applied to the large number of samples (n
      = 2770) generated during the survey and when combined with a manual DNA
      extraction protocol had a low failure rate of 6%. Of the early stage 'cod-like'
      eggs (1.2-1.75 mm diameter) positively identified: 34% were cod, 8% haddock and
      58% whiting. As previous stock estimates based on egg surveys for Irish Sea cod
      assumed that the majority of 'cod-like' eggs were from cod, the TaqMan results
      confirm that there was probably substantial contamination by eggs of whiting and
      haddock that would have inflated estimates of the stock biomass.

PMID- 15723680
TI  - Standardizing for microsatellite length in comparisons of genetic diversity.
AB  - Mutation rates at microsatellites tend to increase with the number of repeats of
      the motif, leading to higher levels of polymorphism at long microsatellites. To
      standardize levels of diversity when microsatellites differ in size, we
      investigate the relationship between tract length and variation and provide a
      formula to adjust allelic richness to a fixed mean number of repeats in the
      specific case of chloroplast microsatellites. A comparison between 39 loci from
      eight species of conifers (where chloroplast DNA is paternally inherited) and 64
      loci from 12 species of angiosperms (where chloroplast DNA is generally
      predominantly maternally inherited) indicates that the greater allelic richness
      found in conifers remains significant after controlling for number of repeats.
      The approach stresses the advantage of reporting variation in number of repeats
      instead of relative fragment sizes.

PMID- 15723681
TI  - Universal primers and PCR of gut contents to study marine invertebrate diets.
AB  - Determining the diets of marine invertebrates by gut content analysis is
      problematic. Many consumed organisms become unrecognizable once partly digested,
      while those with hard remains (e.g. diatom skeletons) may bias the analysis.
      Here, we adapt DNA-based methods similar to those used for microbial diversity
      surveys as a novel approach to study the diets of macrophagous (the deep-sea
      amphipods Scopelocheirus schellenbergi and Eurythenes gryllus) and microphagous
      (the bivalve Lucinoma aequizonata) feeders in the deep sea. Polymerase chain
      reaction (PCR) in conjunction with 'universal' primers amplified portions of the
      mitochondrial cytochrome c oxidase I (COI) gene for animals ingested by S.
      schellenbergi and E. gryllus and the 18S rRNA gene for lesser eukaryotes ingested
      by L. aequizonata. Amplified sequences were combined with sequences from GenBank
      to construct phylogenetic trees of ingested organisms. Our analyses indicate that
      S. schellenbergi, E. gryllus and L. aequizonata diets are considerably more
      diverse than previously thought, casting new light on the foraging strategies of
      these species. Finally, we discuss the strengths and weaknesses of this technique
      and its potential applicability to diet analyses of other invertebrates.

PMID- 15723682
TI  - Bacterial vaginosis--a microbiological and immunological enigma.
AB  - The development of bacterial vaginosis (BV) among women of childbearing age and
      the resulting quantitative and qualitative shift from normally occurring
      lactobacilli in the vagina to a mixture of mainly anaerobic bacteria is a
      microbiological and immunological enigma that so far has precluded the
      formulation of a unifying generally accepted theory on the aetiology and clinical
      course of BV. This critical review highlights some of the more important aspects
      of BV research that could help in formulating new basic ideas respecting the
      biology of BV, not least the importance of the interleukin mediators of local
      inflammatory responses and the bacterial shift from the normally occurring
      lactobacilli species: L. crispatus, L. gasseri, L. jensenii, and L. iners to a
      mixed flora dominated by anaerobic bacteria.

PMID- 15723683
TI  - Expression and role of E-cadherin and CD103beta7 (alphaEbeta7 integrin) on
      cultured mucosal-type mast cells.
AB  - Mucosal-type mast cells (MMC) in the respiratory and/or gut epithelium play
      pivotal roles in the development of allergic inflammation and nematode clearance.
      To determine the role of E-cadherin and alphaEbeta7 integrin in MMC localization
      to the epithelium, we analyzed the epithelial binding of two types of mouse bone
      marrow-derived mast cells: S3-BMMC, which developed in medium containing stem
      cell factor (SCF) plus IL-3, and S39T-BMMC, which developed with SCF, IL-3, IL-9
      and TGF-beta1. The latter cells were more similar to mature MMC than the former
      in terms of mouse mast cell protease (mMCP)-1 expression. FACS analyses revealed
      that S3-BMMC expressed E-cadherin and beta7 integrin but not alphaE integrin,
      whereas S39T-BMMC expressed alphaEbeta7 integrin as well as E-cadherin. Mn2+
      promoted adhesion of S39T-BMMC to the monolayer of E-cadherin+F9 cells. The
      adhesion was suppressed significantly by the combined addition of blocking
      antibodies against integrin alphaE and E-cadherin, whereas either blocking
      antibody alone failed to do so. S3-BMMC adhesion was suppressed by E-cadherin
      blocking antibody but not by alphaE blocking antibody. These results suggested
      that E-cadherin and alphaEbeta7 integrin, which are expressed on MMC-analog S39T
      BMMC, play an important role in mast cell-epithelial cell interaction through
      homophilic as well as heterophilic binding to the epithelial E-cadherin molecule.

PMID- 15723684
TI  - Design of a multiplex PCR for Streptococcus pneumoniae, Haemophilus influenzae,
      Mycoplasma pneumoniae and Chlamydophila pneumoniae to be used on sputum samples.
AB  - A multiplex PCR (mPCR) was developed for simultaneous detection of specific genes
      for Streptococcus pneumoniae (lytA), Mycoplasma pneumoniae (P1), Chlamydophila
      pneumoniae (ompA), and Haemophilus influenzae (16S rRNA, with verification PCR
      for P6). When the protocol was tested on 257 bacterial strains belonging to 37
      different species, no false negatives and only one false positive were noted. One
      Streptococcus mitis out of thirty was positive for lytA. In a pilot application
      study of 81 sputum samples from different patients with suspected lower
      respiratory tract infection (LRTI), mPCR identified S. pneumoniae in 25 samples,
      H. influenzae in 29, M. pneumoniae in 3, and C. pneumoniae in 1. All samples
      culture positive for S. pneumoniae (n=15) and H. influenzae (n=15) were mPCR
      positive for the same bacteria. In a pilot control study with nasopharyngeal
      swabs and aspirates from 10 healthy adults, both culture and mPCR were negative.
      No PCR inhibition was found in any of the mPCR-negative sputum or nasopharyngeal
      samples. Whether all samples identified as positive by mPCR are truly positive in
      an aetiological perspective regarding LRTI remains to be evaluated in a well
      defined patient material. In conclusion, the mPCR appears to be a promising tool
      in the aetiological diagnostics of LRTI.

PMID- 15723685
TI  - Biology of the smooth muscle cells in human atherosclerosis.
AB  - The aim of this study was to reconstruct dynamic biological steps of human
      atherosclerosis at different ages of life and, in particular, to clarify the role
      of the smooth muscle cells (SMCs) by means of evaluation of several markers
      implicated in proliferative diseases (c-fos, proliferating cell nuclear antigen:
      PCNA, apoptosis, chromosome 7). We examined the biological features of 67
      atherosclerotic arterial lesions obtained from fetuses, infants, young people and
      adults. From each case serial sections were stained for histological examination,
      PCNA, c-fos and apoptosis detection by immunohistochemical methods and for
      chromosome 7 number evaluation by fluorescence in situ hybridization. In coronary
      specimens of fetuses we observed SMCs with c-fos positivity. In infant lesions
      the predominant result was positivity for PCNA. Similar results were obtained
      from the plaques from young subjects with a greater presence of PCNA-positive
      cells. In adult subjects numerous apoptotic cells were present in the stable
      plaques, whereas in the unstable plaques we frequently detected joint positivity
      for both PCNA and c-fos gene and supernumerary chromosomes 7. During the
      evolution of the atherosclerotic process we observed a biological modulation of
      SMC proliferation, which begins after activation of the c-fos gene, increases
      during progression of the lesion and declines in stable plaques, when apoptosis
      increases. In unstable plaques, the same early steps observed in fetus and infant
      arteries occur. The observation in some cases of chromosome 7 alterations,
      markers of tumorigenesis, suggests the possible transformation of an advanced
      atherosclerotic plaque into a neoplastic-like process.

PMID- 15723686
TI  - High doses of nandrolone decanoate reduce volume of testis and length of
      seminiferous tubules in rats.
AB  - Anabolic-androgenic steroid (AAS) compounds rank among the drugs most widely
      abused with the goal of improving athletic ability, appearance, or muscle mass.
      It has been shown that these compounds have adverse effects on human and animal
      physiology and sperm quality, but quantitative structural changes of the testis
      have received less attention. The present study was conducted to evaluate the
      effects of nandrolone decanoate, which is one of the AAS compounds, on testis
      weight and volume, diameter and length of seminiferous tubules in rats by
      unbiased stereological methods. Adult rats were divided into three groups. The
      first comprised control rats; the second and third groups received low and high
      doses of nandrolone decanoate for 14 weeks. The rats were then left untreated for
      14 weeks. After removal of the testis, stereological study of these tissues
      showed that the mean volume of testis and length of the seminiferous tubules in
      the animals that received high doses of nandrolone decanoate were reduced
      approximately 32% (p<0.01) and approximately 31% (p<0.04), respectively, in
      comparison with the control group. It can be concluded that the high doses of
      nandrolone decanoate produce structural changes in the rat testis that remain 14
      weeks after stopping injection of the drug.

PMID- 15723687
TI  - Evidence of Rickettsia spp. infection in Sweden: a clinical, ultrastructural and
      serological study.
AB  - Sweden is an area potentially endemic for spotted fever rickettsioses. Rickettsia
      helvetica has been isolated from its tick vector Ixodes ricinus, and in a handful
      of cases linked to human disease. This study demonstrates for the first time in
      Sweden the transmission of rickettsial infection after a tick bite and the attack
      rate in an endemic area. We present three cases of documented rickettsial
      infection and a prospective serological study of Swedish recruits who were
      trained in the area where the patients lived and showed seroconversion to spotted
      fever rickettsiae. All patients showed a four-fold increase in antibody titer to
      the spotted fever rickettsia, R. helvetica, and immunohistochemical examination
      revealed rickettsia-like organisms in the walls of skin capillaries and veins.
      Electron microscopy showed organisms resembling R. helvetica and immunogold
      labeling with two anti-rickettsial antibodies demonstrated specific labeling of
      the rickettsial organisms in the skin biopsy specimens. Eight of the thirty-five
      recruits showed a four-fold increase in IgG titer reflecting a high rate of
      exposure. The results of this study demonstrate that spotted fever rickettsioses
      should be taken into consideration in the diagnosis of tick-transmitted
      infections in Sweden.

PMID- 15723688
TI  - Carcinoid tumour metastatic to the orbit with infiltration to the extraocular
      orbital muscle.
AB  - Ninety-three percent of symptomatic patients with small intestinal carcinoid
      tumours have metastases. The most common sites of metastases are lymph nodes and
      liver. Orbital metastases have rarely been described and the majority of them
      involve the choroid rather than extraocular orbital structures. We report a
      patient who developed proptosis, impairment of vision and reduced ocular motility
      on the left side, eighteen months after operation for primary intestinal
      carcinoid tumour with hepatic metastases. CT and MR studies revealed the tumour
      mass infiltrating the inferior rectus muscle. Biopsy examined by imprint and
      frozen section showed tumour consistent with metastatic carcinoid. The tumour was
      removed. HE and staining for cytokeratin, chromogranin, NSE, serotonin,
      somatostatin and gastrin showed that the tumour tissue corresponded to that of
      the primary intestinal carcinoid tumour. Intramuscular orbital metastasis from a
      carcinoid tumour is a rare occurrence. Diagnosis may be difficult, especially
      where no evidence of primary carcinoid tumour is present. Metastatic orbital
      carcinoid should be suspected in patients with a clinical history of carcinoid
      tumour and who develop ocular complaints and mass lesion in the orbit. Complete
      surgical removal of the tumour is important for optimal restitution of vision and
      eye movements.

PMID- 15723689
TI  - Endometrial adenosquamous carcinoma with osteoclast-like giant cells:
      immunohistochemistry and histogenesis.
AB  - Primary extraskeletal epithelial neoplasms containing osteoclast-like giant cells
      (OGCs) are rare. We herein describe a case of adenosquamous carcinoma that
      developed in the endometrium together with non-neoplastic OGCs. The patient was a
      72-year-old woman who underwent radical hysterectomy with salpingo-oophorectomy
      and lymph node dissection after being diagnosed with uterine cancer.
      Histologically, the tumor was found to be an adenosquamous carcinoma containing a
      large number of OGCs and mononuclear cells (MNCs) that had infiltrated into the
      stroma. Immunohistochemically, the OGCs and MNCs stained strongly positive for KP
      1 and alpha-1-antichymotrypsin, and negative for the epithelial markers
      epithelial membrane antigen (EMA) and cytokeratins. These findings suggest that
      the OGCs and MNCs in this patient's tumor originated from monocytes/histiocytes,
      and most likely developed as part of the stromal reaction to the neoplasm.

PMID- 15723690
TI  - Primary leiomyoma of the ovary co-existing with serous cystadenofibroma.
AB  - A 48-year-old woman with a 14 cm left ovarian mass had total abdominal
      hysterectomy and bilateral salpingo-oophorectomy. On cut section the tumor had a
      solid and a cystic component. There was a 2.5 cm nodule attached to the cyst
      wall. Sections taken from the solid component revealed a tumor composed of
      interlacing bundles of fusiform cells, resembling a leiomyoma. Smooth muscle
      actin positivity confirmed the diagnosis. Sections taken from the nodule in the
      cystic part revealed an adenofibroma. There was an SMA positive area in the cyst
      wall which we think is the possible origin of the leiomyoma. As far as we know,
      this is the first case of a co-existing leiomyoma and serous cystadenofibroma in
      the ovary, and we think it will broaden the histological spectrum of primary
      ovarian leiomyomas.

PMID- 15723691
TI  - Primary sinonasal ameloblastoma.
AB  - A case of primary ameloblastoma of the right sinonasal tract in a 66-year-old man
      is reported. The tumour presented as a radiographically solid mass filling the
      right nasal cavity and sinuses and without continuity with maxillary alveola.
      After radical surgery plus postoperative radiotherapy, the patient has pursued a
      non-aggressive clinical course after nine months of follow-up. The paper reviews
      the clinico-pathological features of this rare tumour and supports the theory of
      its sinonasal epithelium origin.

PMID- 15723693
TI  - Atlas - a data warehouse for integrative bioinformatics.
AB  - BACKGROUND: We present a biological data warehouse called Atlas that locally
      stores and integrates biological sequences, molecular interactions, homology
      information, functional annotations of genes, and biological ontologies. The goal
      of the system is to provide data, as well as a software infrastructure for
      bioinformatics research and development. DESCRIPTION: The Atlas system is based
      on relational data models that we developed for each of the source data types.
      Data stored within these relational models are managed through Structured Query
      Language (SQL) calls that are implemented in a set of Application Programming
      Interfaces (APIs). The APIs include three languages: C++, Java, and Perl. The
      methods in these API libraries are used to construct a set of loader
      applications, which parse and load the source datasets into the Atlas database,
      and a set of toolbox applications which facilitate data retrieval. Atlas stores
      and integrates local instances of GenBank, RefSeq, UniProt, Human Protein
      Reference Database (HPRD), Biomolecular Interaction Network Database (BIND),
      Database of Interacting Proteins (DIP), Molecular Interactions Database (MINT),
      IntAct, NCBI Taxonomy, Gene Ontology (GO), Online Mendelian Inheritance in Man
      (OMIM), LocusLink, Entrez Gene and HomoloGene. The retrieval APIs and toolbox
      applications are critical components that offer end-users flexible, easy,
      integrated access to this data. We present use cases that use Atlas to integrate
      these sources for genome annotation, inference of molecular interactions across
      species, and gene-disease associations. CONCLUSION: The Atlas biological data
      warehouse serves as data infrastructure for bioinformatics research and
      development. It forms the backbone of the research activities in our laboratory
      and facilitates the integration of disparate, heterogeneous biological sources of
      data enabling new scientific inferences. Atlas achieves integration of diverse
      data sets at two levels. First, Atlas stores data of similar types using common
      data models, enforcing the relationships between data types. Second, integration
      is achieved through a combination of APIs, ontology, and tools. The Atlas
      software is freely available under the GNU General Public License at:
      http://bioinformatics.ubc.ca/atlas/

PMID- 15723694
TI  - The role of NGOs in global health research for development.
AB  - BACKGROUND: Global health research is essential for development. A major issue is
      the inequitable distribution of research efforts and funds directed towards
      populations suffering the world's greatest health problems. This imbalance is
      fostering major attempts at redirecting research to the health problems of low
      and middle income countries. Following the creation of the Coalition for Global
      Health Research - Canada (CGHRC) in 2001, the Canadian Society for International
      Health (CSIH) decided to review the role of non-governmental organizations (NGOs)
      in global health research. This paper highlights some of the prevalent thinking
      and is intended to encourage new thinking on how NGOs can further this role.
      APPROACH: This paper was prepared by members of the Research Committee of the
      CSIH, with input from other members of the Society. Persons working in various
      international NGOs participated in individual interviews or group discussions on
      their involvement in different types of research activities. Case studies
      illustrate the roles of NGOs in global health research, their perceived strengths
      and weaknesses, and the constraints and opportunities to build capacity and
      develop partnerships for research. HIGHLIGHTS: NGOs are contributing at all
      stages of the research cycle, fostering the relevance and effectiveness of the
      research, priority setting, and knowledge translation to action. They have a key
      role in stewardship (promoting and advocating for relevant global health
      research), resource mobilization for research, the generation, utilization and
      management of knowledge, and capacity development. Yet, typically, the
      involvement of NGOs in research is downstream from knowledge production and it
      usually takes the form of a partnership with universities or dedicated research
      agencies. CONCLUSION: There is a need to more effectively include NGOs in all
      aspects of health research in order to maximize the potential benefits of
      research. NGOs, moreover, can and should play an instrumental role in coalitions
      for global health research, such as the CGHRC. With a renewed sense of purpose
      and a common goal, NGOs and their partners intend to make strong and lasting
      inroads into reducing the disease burden of the world's most affected populations
      through effective research action.

PMID- 15723695
TI  - Umbilical metastases: current viewpoint.
AB  - BACKGROUND: Umbilical metastases from a malignant neoplasm, also termed Sister
      Mary Joseph's nodule, are not commonly reported in the English literature, and
      they have usually been considered as a sign of a poor prognosis for the patient.
      The present article reports on the current view point on umbilical metastasis
      besides discussing the epidemiology, clinical presentation, pathophysiology and
      treatment. METHOD: A search of Pubmed was carried out using the term 'umblic*'
      and 'metastases' or metastasis' revealed no references. Another search was made
      using the term "Sister Joseph's nodule" or sister Joseph nodule" that revealed 99
      references. Of these there were 14 review articles, however when the search was
      limited to English language it yielded only 20 articles. Articles selected from
      these form the basis of this report along with cross references. RESULTS: The
      primary lesions usually arise from gastrointestinal or genitourinary tract
      malignancies and may be the presenting symptom or sign of a primary tumour in an
      unknown site. CONCLUSION: A careful evaluation of all umbilical lesions,
      including an early biopsy if appropriate, is recommended. Recent studies suggest
      an aggressive surgical approach combined with chemotherapy for such patients may
      improve survival.

PMID- 15723696
TI  - Rural Indian tribal communities: an emerging high-risk group for HIV/AIDS.
AB  - BACKGROUND: Rural Indian tribes are anthropologically distinct with unique
      cultures, traditions and practices. Over the years, displacement and rapid
      acculturation of this population has led to dramatic changes in their socio
      cultural and value systems. Due to a poor health infrastructure, high levels of
      poverty and ignorance, these communities are highly vulnerable to various health
      problems, especially, communicable diseases including HIV/AIDS. Our study sought
      to assess knowledge, attitudes and practices regarding sexuality, and the risk
      factors associated with the spread of HIV/AIDS and STDs among these communities.
      METHODS: A nested cross sectional study was undertaken as part of the on going
      Reproductive and Child Health Survey. A total of 5,690 participants age 18-44
      were recruited for this study. Data were obtained through home interviews, and
      focused on socio-demographics, knowledge, attitudes and behaviors regarding
      sexuality, HIV/AIDS and other STDs. RESULTS: The study revealed that only 22% of
      adults had even heard of AIDS, and 18 % knew how it is transmitted. In addition,
      only 5% knew that STDs and AIDS were related to each other. AIDS awareness among
      women was lower compared to men (14% vs.30 %). Regarding sexual practices, 35% of
      the respondents reported having had extramarital sexual encounters, with more
      males than females reporting extramarital affairs. CONCLUSION: Lack of awareness,
      permissiveness of tribal societies for premarital or extra-marital sexual
      relationships, and sexual mixing patterns predispose these communities to
      HIV/AIDS and STD infections. There is a dire need for targeted interventions in
      order to curtail the increasing threat of HIV and other STDs among these
      vulnerable populations.

PMID- 15723697
TI  - Comparative promoter region analysis powered by CORG.
AB  - BACKGROUND: Promoters are key players in gene regulation. They receive signals
      from various sources (e.g. cell surface receptors) and control the level of
      transcription initiation, which largely determines gene expression. In
      vertebrates, transcription start sites and surrounding regulatory elements are
      often poorly defined. To support promoter analysis, we present CORG
      http://corg.molgen.mpg.de, a framework for studying upstream regions including
      untranslated exons (5' UTR). DESCRIPTION: The automated annotation of promoter
      regions integrates information of two kinds. First, statistically significant
      cross-species conservation within upstream regions of orthologous genes is
      detected. Pairwise as well as multiple sequence comparisons are computed. Second,
      binding site descriptions (position-weight matrices) are employed to predict
      conserved regulatory elements with a novel approach. Assembled EST sequences and
      verified transcription start sites are incorporated to distinguish exonic from
      other sequences. As of now, we have included 5 species in our analysis pipeline
      (man, mouse, rat, fugu and zebrafish). We characterized promoter regions of
      16,127 groups of orthologous genes. All data are presented in an intuitive way
      via our web site. Users are free to export data for single genes or access larger
      data sets via our DAS server http://tomcat.molgen.mpg.de:8080/das. The benefits
      of our framework are exemplarily shown in the context of phylogenetic profiling
      of transcription factor binding sites and detection of microRNAs close to
      transcription start sites of our gene set. CONCLUSION: The CORG platform is a
      versatile tool to support analyses of gene regulation in vertebrate promoter
      regions. Applications for CORG cover a broad range from studying evolution of DNA
      binding sites and promoter constitution to the discovery of new regulatory
      sequence elements (e.g. microRNAs and binding sites).

PMID- 15723698
TI  - Out of Tanganyika: genesis, explosive speciation, key-innovations and
      phylogeography of the haplochromine cichlid fishes.
AB  - BACKGROUND: The adaptive radiations of cichlid fishes in East Africa are well
      known for their spectacular diversity and their astonishingly fast rates of
      speciation. About 80% of all 2,500 cichlid species in East Africa, and virtually
      all cichlid species from Lakes Victoria (approximately 500 species) and Malawi
      (approximately 1,000 species) are haplochromines. Here, we present the most
      extensive phylogenetic and phylogeographic analysis so far that includes about
      100 species and is based on about 2,000 bp of the mitochondrial DNA. RESULTS: Our
      analyses revealed that all haplochromine lineages are ultimately derived from
      Lake Tanganyika endemics. We find that the three most ancestral lineages of the
      haplochromines sensu lato are relatively species poor, albeit widely distributed
      in Africa, whereas a fourth newly defined lineage - the 'modern haplochromines' -
      contains an unparalleled diversity that makes up more than 7% of the worlds'
      approximately 25,000 teleost species. The modern haplochromines' ancestor, most
      likely a riverine generalist, repeatedly gave rise to similar ecomorphs now found
      in several of the species flocks. Also, the Tanganyikan Tropheini are derived
      from that riverine ancestor suggesting that they successfully re-colonized Lake
      Tanganyika and speciated in parallel to an already established cichlid adaptive
      radiation. In contrast to most other known examples of adaptive radiations, these
      generalist ancestors were derived from highly diverse and specialized endemics
      from Lake Tanganyika. A reconstruction of life-history traits revealed that in an
      ancestral lineage leading to the modern haplochromines the characteristic egg
      spots on anal fins of male individuals evolved. CONCLUSION: We conclude that Lake
      Tanganyika is the geographic and genetic cradle of all haplochromine lineages. In
      the ancestors of the replicate adaptive radiations of the 'modern
      haplochromines', behavioral (maternal mouthbrooding), morphological (egg-spots)
      and sexually selected (color polymorphism) key-innovations arose. These might be 
      together with the ecological opportunity that the habitat diversity of the large
      lakes provides - responsible for their evolutionary success and their propensity
      for explosive speciation.

PMID- 15723699
TI  - Determining the quality of educational climate across multiple undergraduate
      teaching sites using the DREEM inventory.
AB  - BACKGROUND: Our obstetrics and gynaecology undergraduate teaching module
      allocates 40-50 final year medical students to eight teaching hospital sites in
      the West Midlands region. Based on student feedback and concerns relating to the
      impact of new curriculum changes, we wished to objectively assess whether the
      educational environment perceived by students varied at different teaching
      hospital centres, and whether the environment was at an acceptable standard.
      METHODS: A Dundee Ready Education Environment (DREEM) Questionnaire, a measure of
      educational environment, was administered to 206 students immediately following
      completion of the teaching module. RESULTS: The overall mean DREEM score was
      139/200 (70%). There were no differences in the education climate between the
      teaching centres. CONCLUSION: Further research on the use of DREEM inventory,
      with follow up surveys, may be useful for educators to ensure and maintain high
      quality educational environments despite students being placed at different
      teaching centres.

PMID- 15723700
TI  - A comparative study of reaction times between type II diabetics and non
      diabetics.
AB  - BACKGROUND: Aging has been shown to slow reflexes and increase reaction time to
      varied stimuli. However, the effect of Type II diabetes on these same reaction
      times has not been reported. Diabetes affects peripheral nerves in the
      somatosensory and auditory system, slows psychomotor responses, and has cognitive
      effects on those individuals without proper metabolic control, all of which may
      affect reaction times. The additional slowing of reaction times may affect every
      day tasks such as balance, increasing the probability of a slip or fall. METHODS:
      Reaction times to a plantar touch, a pure tone auditory stimulus, and rightward
      whole-body lateral movement of 4 mm at 100 mm/s2 on a platform upon which a
      subject stood, were measured in 37 adults over 50 yrs old. Thirteen (mean age =
      60.6 +/- 6.5 years) had a clinical diagnosis of type II diabetes and 24 (mean age
      = 59.4 +/- 8.0 years) did not. Group averages were compared to averages obtained
      from nine healthy younger adult group (mean age = 22.7 +/- 1.2 years). RESULTS:
      Average reaction times for plantar touch were significantly longer in diabetic
      adults than the other two groups, while auditory reaction times were not
      significantly different among groups. Whole body reaction times were
      significantly different among all three groups with diabetic adults having the
      longest reaction times, followed by age-matched adults, and then younger adults.
      CONCLUSION: Whole body reaction time has been shown to be a sensitive indicator
      of differences between young adults, healthy mature adults, and mature diabetic
      adults. Additionally, the increased reaction time seen in this modality for
      subjects with diabetes may be one cause of increased slips and falls in this
      group.

PMID- 15723701
TI  - What is important in evaluating health care quality? An international comparison
      of user views.
AB  - BACKGROUND: Quality of care from the perspective of users is increasingly used in
      evaluating health care performance. Going beyond satisfaction studies, quality of
      care from the users' perspective is conceptualised in two dimensions: the
      importance users attach to aspects of care and their actual experience with these
      aspects. It is well established that health care systems differ in performance.
      The question in this article is whether there are also differences in what people
      in different health care systems view as important aspects of health care
      quality. The aim is to describe and explain international differences in the
      importance that health care users attach to different aspects of health care.
      METHODS: Data were used from different studies that all used a version of the
      QUOTE-questionnaire that measures user views of health care quality in two
      dimensions: the importance that users attach to aspects of care and their actual
      experience. Data from 12 European countries and 5133 individuals were used. They
      were analysed using multi-level analysis. RESULTS: Although most of the
      variations in importance people attach to aspects of health care is located at
      the individual level, there are also differences between countries. The ranking
      of aspects shows similarities. 'My GP should always take me seriously' was in
      nearly all countries ranked first, while an item about waiting time in the GP's
      office was always ranked lowest. CONCLUSION: Differences between countries in how
      health care users value different aspects of care are difficult to explain.
      Further theorising should take into account that importance and performance
      ratings are positively related, that people compare their experiences with those
      of others, and that general and instrumental values might be related through the
      institutions of the health care system.

PMID- 15723703
TI  - Anaphylatoxin C3a receptors in asthma.
AB  - The complement system forms the central core of innate immunity but also mediates
      a variety of inflammatory responses. Anaphylatoxin C3a, which is generated as a
      byproduct of complement activation, has long been known to activate mast cells,
      basophils and eosinophils and to cause smooth muscle contraction. However, the
      role of C3a in the pathogenesis of allergic asthma remains unclear. In this
      review, we examine the role of C3a in promoting asthma. Following allergen
      challenge, C3a is generated in the lung of subjects with asthma but not healthy
      subjects. Furthermore, deficiency in C3a generation or in G protein coupled
      receptor for C3a abrogates allergen-induced responses in murine models of
      pulmonary inflammation and airway hyperresponsiveness. In addition, inhibition of
      complement activation or administration of small molecule inhibitors of C3a
      receptor after sensitization but before allergen challenge inhibits airway
      responses. At a cellular level, C3a stimulates robust mast cell degranulation
      that is greatly enhanced following cell-cell contact with airway smooth muscle
      (ASM) cells. Therefore, C3a likely plays an important role in asthma primarily by
      regulating mast cell-ASM cell interaction.

PMID- 15723702
TI  - Fructose, insulin resistance, and metabolic dyslipidemia.
AB  - Obesity and type 2 diabetes are occurring at epidemic rates in the United States
      and many parts of the world. The "obesity epidemic" appears to have emerged
      largely from changes in our diet and reduced physical activity. An important but
      not well-appreciated dietary change has been the substantial increase in the
      amount of dietary fructose consumption from high intake of sucrose and high
      fructose corn syrup, a common sweetener used in the food industry. A high flux of
      fructose to the liver, the main organ capable of metabolizing this simple
      carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads
      to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG)
      synthesis, driven by the high flux of glycerol and acyl portions of TG molecules
      from fructose catabolism. These metabolic disturbances appear to underlie the
      induction of insulin resistance commonly observed with high fructose feeding in
      both humans and animal models. Fructose-induced insulin resistant states are
      commonly characterized by a profound metabolic dyslipidemia, which appears to
      result from hepatic and intestinal overproduction of atherogenic lipoprotein
      particles. Thus, emerging evidence from recent epidemiological and biochemical
      studies clearly suggests that the high dietary intake of fructose has rapidly
      become an important causative factor in the development of the metabolic
      syndrome. There is an urgent need for increased public awareness of the risks
      associated with high fructose consumption and greater efforts should be made to
      curb the supplementation of packaged foods with high fructose additives. The
      present review will discuss the trends in fructose consumption, the metabolic
      consequences of increased fructose intake, and the molecular mechanisms leading
      to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia.

PMID- 15723704
TI  - Resorbable screws versus pins for optimal transplant fixation (SPOT) in anterior
      cruciate ligament replacement with autologous hamstring grafts: rationale and
      design of a randomized, controlled, patient and investigator blinded trial
      [ISRCTN17384369].
AB  - BACKGROUND: Ruptures of the anterior cruciate ligament (ACL) are common injuries
      to the knee joint. Arthroscopic ACL replacement by autologous tendon grafts has
      established itself as a standard of care. Data from both experimental and
      observational studies suggest that surgical reconstruction does not fully restore
      knee stability. Persisting anterior laxity may lead to recurrent episodes of
      giving-way and cartilage damage. This might at least in part depend on the method
      of graft fixation in the bony tunnels. Whereas resorbable screws are easy to
      handle, pins may better preserve graft tension. The objective of this study is to
      determine whether pinning of ACL grafts reduces residual anterior laxity six
      months after surgery as compared to screw fixation. DESIGN/METHODS: SPOT is a
      randomised, controlled, patient and investigator blinded trial conducted at a
      single academic institution. Eligible patients are scheduled to arthroscopic ACL
      repair with triple-stranded hamstring grafts, conducted by a single, experienced
      surgeon. Intraoperatively, subjects willing to engage in this study will be
      randomised to transplant tethering with either resorbable screws or resorbable
      pins. No other changes apply to locally established treatment protocols. Patients
      and clinical investigators will remain blinded to the assigned fixation method
      until the six-month follow-up examination. The primary outcome is the side-to
      side (repaired to healthy knee) difference in anterior translation as measured by
      the KT-1000 arthrometer at a defined load (89 N) six months after surgery. A
      sample size of 54 patients will yield a power of 80% to detect a difference of
      1.0 mm +/- standard deviation 1.2 mm at a two-sided alpha of 5% with a t-test for
      independent samples. Secondary outcomes (generic and disease-specific measures of
      quality of life, magnetic resonance imaging morphology of transplants and
      devices) will be handled in an exploratory fashion. CONCLUSION: SPOT aims at
      showing a reduction in anterior knee laxity after fixing ACL grafts by pins
      compared to screws.

PMID- 15723705
TI  - A phase I study of dexosome immunotherapy in patients with advanced non-small
      cell lung cancer.
AB  - BACKGROUND: There is a continued need to develop more effective cancer
      immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high
      levels of a narrow spectrum of cell proteins represent a novel platform for
      delivering high levels of antigen in conjunction with costimulatory molecules. We
      performed this study to test the safety, feasibility and efficacy of autologous
      dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in
      patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study
      enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9)
      NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to
      generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and
      MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals.
      RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three
      formulations of DEX were evaluated; all were well tolerated with only grade 1-2
      adverse events related to the use of DEX (injection site reactions (N = 8), flu
      like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first
      dose of DEX until disease progression was 30 to 429+ days. Three patients had
      disease progression before the first DEX dose. Survival of patients after the
      first DEX dose was 52-665+ days. DTH reactivity against MAGE peptides was
      detected in 3/9 patients. Immune responses were detected in patients as follows:
      MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4.
      CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well
      tolerated in patients with advanced NSCLC. Some patients experienced long term
      stability of disease and activation of immune effectors.

PMID- 15723706
TI  - Illness-related practices for the management of childhood malaria among the
      Bwatiye people of north-eastern Nigeria.
AB  - BACKGROUND: A wide range of childhood illnesses are accompanied by fever,,
      including malaria. Child mortality due to malaria has been attributed to poor
      health service delivery system and ignorance. An assessment of a mother's ability
      to recognize malaria in children under-five was carried out among the Bwatiye, a
      poorly-served minority ethnic group in north-eastern Nigeria. METHODS: A three
      stage research design involving interviews, participatory observation and
      laboratory tests was used to seek information from 186 Bwatiye mothers about
      their illness-related experiences with childhood fevers. RESULTS: Mothers
      classified malaria into male (fever that persists for longer than three days) and
      female (fever that goes away within three days) and had a system of determining
      when febrile illness would not be regarded as malaria. Most often, malaria would
      be ignored in the first 2 days before seeking active treatment. Self-medication
      was the preferred option. Treatment practices and sources of help were influenced
      by local beliefs, the parity of the mother and previous experience with child
      mortality. CONCLUSION: The need to educate mothers to suspect malaria in every
      case of febrile illness and take appropriate action in order to expose the
      underlying "evil" will be more acceptable than an insistence on replacing local
      knowledge with biological epidemiology of malaria. The challenge facing health
      workers is to identify and exploit local beliefs about aetiology in effecting
      management procedures among culturally different peoples, who may not accept the
      concept of biological epidemiology.

PMID- 15723707
TI  - Polymorphisms in immunoregulatory genes and the risk of histologic
      chorioamnionitis in Caucasoid women: a case control study.
AB  - BACKGROUND: Chorioamnionitis is a common underlying cause of preterm birth (PTB).
      It is hypothesised that polymorphisms in immunoregulatory genes influence the
      host response to infection and subsequent preterm birth. The relationship between
      histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11
      immunoregulatory genes was examined in a case-control study. METHODS: Placentas
      of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for
      histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1,
      tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1
      (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by
      polymerase chain reaction and sequence specific primers. Multivariable logistic
      regression including demographic and genetic variables and Kaplan-Meier survival
      analyses of genotype frequencies and pregnancy outcome were performed. RESULTS:
      Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis.
      Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio
      (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were
      positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG)
      haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype
      (MOR 0.2, P = 0.04) were negatively associated. CONCLUSION: These findings
      demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and
      TGFB1 may influence susceptibility to chorioamnionitis.

PMID- 15723708
TI  - Oral vitamin B12 therapy in the primary care setting: a qualitative and
      quantitative study of patient perspectives.
AB  - BACKGROUND: Although oral replacement with high doses of vitamin B12 is both
      effective and safe for the treatment of B12 deficiency, little is known about
      patients' views concerning the acceptability and effectiveness of oral B12. We
      investigated patient perspectives on switching from injection to oral B12
      therapy. METHODS: This study involved a quantitative arm using questionnaires and
      a qualitative arm using semi-structured interviews, both to assess patient views
      on injection and oral therapy. Patients were also offered a six-month trial of
      oral B12 therapy. One hundred and thirty-three patients who receive regular B12
      injections were included from three family practice units (two hospital-based
      academic clinics and one community health centre clinic) in Toronto. RESULTS:
      Seventy-three percent (63/86) of respondents were willing to try oral B12. In a
      multivariate analysis, patient factors associated with a "willingness to switch"
      to oral B12 included being able to get to the clinic in less than 30 minutes (OR
      9.3, 95% CI 2.2-40.0), and believing that frequent visits to the health care
      provider (OR 5.4, 95% CI 1.1-26.6) or the increased costs to the health care
      system (OR 16.7, 95% CI 1.5-184.2) were disadvantages of injection B12. Fifty
      five patients attempted oral therapy and 52 patients returned the final
      questionnaire. Of those who tried oral therapy, 76% (39/51) were satisfied and
      71% (39/55) wished to permanently switch. Factors associated with permanently
      switching to oral therapy included believing that the frequent visits to the
      health care provider (OR 35.4, 95% CI 2.9-432.7) and travel/parking costs (OR
      8.7, 95% CI 1.2-65.3) were disadvantages of injection B12. Interview participants
      consistently cited convenience as an advantage of oral therapy. CONCLUSION:
      Switching patients from injection to oral B12 is both feasible and acceptable to
      patients. Oral B12 supplementation is well received largely due to increased
      convenience. Clinicians should offer oral B12 therapy to their patients who are
      currently receiving injections, and newly diagnosed B12-deficient patients who
      can tolerate and are compliant with oral medications should be offered oral
      supplementation.

PMID- 15723710
TI  - Sarcocystosis of chital-dhole: conditions for evolutionary stability of a
      predator parasite mutualism.
AB  - BACKGROUND: For parasites with a predator-prey life cycle, the completion of the
      life cycle often depends on consumption of parasitized prey by the predator. In
      the case of such parasite species the predator and the parasite have common
      interests and therefore a mutualistic relationship is possible. Some evidence of
      a predator-parasite mutualism was reported from spotted deer or chital (Axix
      axis) as a prey species, dhole or Indian wild-dog (Cuon alpinus) as the predator
      and a protozoan (Sarcocystis axicuonis) as the parasite. We examine here, with
      the help of a model, the ecological conditions necessary for the evolution and
      stability of such a mutualistic relationship. A two - level game theory model was
      designed in which the payoff of a parasite is decided not only by alternative
      parasite strategies but also by alternative host strategies and vice versa.
      Conditions for ESS were examined. RESULTS: A tolerant predator strategy and a low
      or moderately virulent parasite strategy which together constitute mutualism are
      stable only at a high frequency of recycling of parasite and a substantial prey -
      capture benefit to the predator. Unlike the preliminary expectation, parasite
      will not evolve towards reduced virulence, but reach an optimum moderate level of
      virulence. CONCLUSION: The available data on the behavioral ecology of dhole and
      chital suggest that they are likely to meet the stability criteria and therefore
      a predator-parasite mutualism can be stable in this system. The model also points
      out the gaps in the current data and could help directing further empirical work.

PMID- 15723709
TI  - Docetaxel plus cisplatin is effective for patients with metastatic breast cancer
      resistant to previous anthracycline treatment: a phase II clinical trial.
AB  - BACKGROUND: Patients with metastatic breast cancer (MBC) are frequently exposed
      to high cumulative doses of anthracyclines and are at risk of resistance and
      cardiotoxicity. This phase II trial evaluated the efficacy and toxicity of
      docetaxel plus cisplatin, as salvage chemotherapy in patients with MBC resistant
      to prior anthracyclines. METHODS: Patients with MBC that had progressed after at
      least one prior chemotherapy regimen containing anthracyclines received docetaxel
      75 mg/m2 followed by cisplatin 60 mg/m2 every 3 weeks for a maximum of 6 cycles
      or until disease progression. RESULTS: Between Jan 2000 and May 2002, 24 patients
      with tumors primary resistant and 15 with secondary resistant disease were
      accrued. All 39 patients were evaluable for safety and 36 for efficacy. The
      objective response rate was 31% (95% CI, 16-45%) with 3 complete responses. The
      median time to disease progression was 7 months, and the median overall survival
      was 23 months (median follow-up of 41 months). Neutropenia was the most
      frequently observed severe hematologic toxicity (39% of patients), whereas
      asthenia and nausea were the most common non-hematologic toxicities. No treatment
      related death was observed. CONCLUSION: In conclusion, we found docetaxel plus
      cisplatin to be an active and safe chemotherapy regimen for patients with MBC
      resistant to anthracyclines.

PMID- 15723711
TI  - The RAD51 gene family, genetic instability and cancer.
AB  - Inefficient repair or mis-repair of DNA damage can cause genetic instability, and
      defects in some DNA repair genes are associated with rare human cancer-prone
      disorders. In the last few years, homologous recombination has been found to be a
      key pathway in human cells for the repair of severe DNA damage such as double
      strand breaks. The RAD51 family of genes, including RAD51 and the five RAD51-like
      genes (XRCC2, XRCC3, RAD51L1, RAD51L2, RAD51L3) are known to have crucial non
      redundant roles in this pathway. Current knowledge of the functions of the RAD51
      gene family is reviewed, as well as the evidence for extensive genetic
      instability arising from loss of their activity. Reports of potential
      associations between variants of RAD51 family genes and specific forms of cancer
      are summarized, but it is seen that many of these studies have relatively low
      statistical power. As yet these data provide only tantalizing suggestions of
      modified cancer risks arising from polymorphisms, mutations, or changes in
      expression of the RAD51 gene family, and there is still a lot to learn before
      firm conclusions can be made.

PMID- 15723712
TI  - Induction by lysophosphatidic acid of peritoneal and pleural metastases of
      intestinal cancers induced by azoxymethane in Wistar rats.
AB  - The effects of 1-oleoyl lysophosphatidic acid on the induction of metastasis from
      intestinal adenocarcinomas induced in rats by azoxymethane and on RhoA activity
      in the tumors were investigated in male Wistar rats. Rats were given a weekly
      s.c. injection of azoxymethane (7.4 mg/kg body weight) for 10 weeks and, from
      week 16, s.c. injection of lysophosphatidic acid (5 or 15 microg/kg body weight)
      every other day until the end of the experiment in week 45. Lysophosphatidic acid
      at both dosages significantly increased the incidence of peritoneal metastasis.
      Its administration at higher dosage also significantly enhanced the development
      of pleural metastasis. Although lysophosphatidic acid at both dosages had little
      or no effect on the location, histologic type, depth of involvement or
      infiltrating growth patterns of the tumors, its administration at both dosages
      significantly increased the incidence of vessel invasion of adenocarcinomas.
      Lysophosphatidic acid also increased the activity of RhoA in the tumors, but not
      the cellular proliferation and vascularity of the colon tumors. Our findings
      indicate that lysophosphatidic acid significantly increased the incidence of
      peritoneal and/or pleural metastases from intestinal adenocarcinomas induced in
      rats by azoxymethane through RhoA activation.

PMID- 15723713
TI  - Limited tumor-initiating activity of phenylethyl isothiocyanate by promotion with
      sodium L-ascorbate in a rat two-stage urinary bladder carcinogenesis model.
AB  - Initiation activity of phenylethyl isothiocyanate (PEITC) was examined in a two
      stage urinary bladder carcinogenesis model. Male 6-week-old Fischer 344 rats were
      fed diet containing 0.1% PEITC for 12 or 24 weeks, with or without subsequent
      administration of 5% sodium l-ascorbate (Na-AsA) in diet until week 48, or for
      the entire experimental period. After 12 weeks of PEITC-treatment, both simple
      hyperplasia and papillary or nodular (PN) hyperplasia had developed in all
      animals, but the majority of these lesions had disappeared at week 48,
      irrespective of the Na-AsA-treatment. The same lesions after 24 weeks of PEITC
      treatment had progressed to dysplasia and carcinoma, in a small number of cases
      by week 48 (6% in incidence for each lesion), but enhancement by the Na-AsA
      treatment was evident only with simple hyperplasias (from 56 to 100% in
      incidence) and PN hyperplasias (from 19 to 56%). The results suggest a limited
      initiation activity of PEITC with induction of irreversible lesions by 24 weeks
      of exposure.

PMID- 15723714
TI  - Mycobacterium tuberculosis infection and FHIT gene alterations in lung cancer.
AB  - Although it is fairly well accepted that pulmonary tuberculosis is a major risk
      factor of lung cancer, the exact molecular mechanisms involved in its
      tumorigenesis are unclear. For this purpose, we have examined the relationship
      between Mycobacterium tuberculosis (M-TB) infection and FHIT gene alteration in
      lung cancer. Tumors with M-TB infection had a slightly higher abnormal FHIT
      protein expression compared with tumors without M-TB infection, although not
      statistically significant (Fisher's exact test, P=0.248). LOH affecting at least
      one locus of the FHIT gene was significantly more frequent in lung cancer
      patients with M-TB infection than in patients without M-TB infection whether
      assessment by univariate testing methods or logistic regression modeling analysis
      (Fisher's exact test P=0.025, logistic regression analysis P=0.012). These
      results indicate that M-TB infection is associated with FHIT gene LOH in lung
      cancer.

PMID- 15723715
TI  - Analysis of combination anti-angiogenesis therapy on markers of coagulation,
      platelet activation and angiogenesis in patients with advanced cancer.
AB  - The effects of combination anti-angiogenesis therapy (marimastat, captopril and
      fragmin) on plasma levels of coagulation initiator tissue factor (TF), platelet
      marker soluble P-selectin and angiogenic vascular endothelial growth factor
      (VEGF) were tested in 25 patients with advanced cancer. They had higher soluble P
      selectin (P<0.001) and TF (P<0.001), but not VEGF (P=0.066) than 25 age and sex
      matched controls. VEGF and TF correlated significantly (r=0.8, P<0.001) in cancer
      patients. Soluble P-selectin, TF and VEGF did not change at 4- and 8-weeks whilst
      on treatment. We provide further evidence linking coagulation and angiogenesis
      but combination anti-angiogenesis therapy does not influence plasma soluble P
      selectin, TF or VEGF.

PMID- 15723716
TI  - Monitoring PDT-induced damage using spectrally resolved reflectance imaging of
      tissue oxygenation.
AB  - Photodynamic therapy (PDT) with chlorin e6 (Chl) was monitored in vivo using
      vital microscopy and Fourier transform spectral imaging (FT-SI). Mammary C26
      colon carcinoma, implanted intradermally in a mouse, was irradiated at 650 nm
      with various radiant exposures, 3 h after administration of 5 mg/kg Chl. The
      photodynamic response (PDR) in the skin flap with tumor was expressed as
      microcirculation disturbances (thrombi formation, multiple embolizations,
      arteriolar occlusion and venous stasis) and, dependent on the radiant exposure,
      was transient or permanent. These biological manifestations were accompanied by a
      change in hemoglobin (Hb)/oxyhemoglobin (HbO2) absorption spectra obtained in
      vivo by FT-SI. False-color mapping of hemoglobin oxygen saturation (OS)
      visualized the alteration of tissue oxygenation. The results demonstrate, for the
      first time, that FT-SI can serve as a sensitive non-invasive tool for OS
      monitoring of PDT effects.

PMID- 15723717
TI  - Evidence for a general cancer susceptibility locus at 3p24 in families with
      hereditary prostate cancer.
AB  - To identify genes that generally increase the risk of cancer, we performed a
      systematic search throughout the genome in 188 families primarily ascertained for
      prostate cancer but which also included individuals with other cancers. We
      observed significant evidence for linkage between susceptibility to all cancers
      and markers at 3p24, with a peak HLOD of 3.08 (P=0.0002). Compared to families
      with less than three other cancers and prostate cancer only, evidence for linkage
      at this region was stronger among families with at least three other cancers.
      This is the first reported example of a genome-wide search for general cancer
      susceptibility genes among hereditary prostate cancer families.

PMID- 15723718
TI  - Association of p73 G4C14-to-A4T14 polymorphism at exon 2 and p53 Arg72Pro
      polymorphism with the risk of endometrial cancer in Japanese subjects.
AB  - To test the association of endometrial cancer with the p73 G4C14-to-A4T14
      polymorphism in exon 2 and the p53 Arg72Pro polymorphism, an incident case
      control study was performed in Japanese subjects. The cases comprised 114
      endometrial cancer patients, and the controls were 320 healthy females and 122
      noncancer female outpatients. An unconditional logistic regression model
      demonstrated a significant association between the p73 AA genotype and an
      increased risk of endometrial cancer (OR=2.82, 95% CI=1.36-5.82), especially of
      type-I tumors (OR=3.24, 95% CI=1.53-6.87). In contrast, there was no significant
      difference in the p53 Arg72Pro genotype frequency between the controls and cases.

PMID- 15723719
TI  - Lung cancer in smoking patients inversely alters the activity of hOGG1 and hNTH1.
AB  - N-Glycosylases excise the damaged adducts from DNA. 7,8-Dihydro-8-oxoguanine in
      human cells is repaired by OGG1 and hNTH1. The activities of hOGG1 and hNTH1 were
      measured, using modified and 32P labelled oligonucleotides, in bronchial biopsy
      samples of smoking patients with non-small cell lung carcinoma. The activity of
      hOOG1 was significantly higher in biopsies from tumour tissues compared with
      intra-individual control samples. On the contrary, the activity of endonuclease
      III homologue, hNTH1, was lower in tumours compared to controls. These opposing
      alterations in DNA repair enzymes may affect cancer growth due to the increased
      formation of AP sites.

PMID- 15723720
TI  - Numerical abnormalities of the Cyclin D1 gene locus on chromosome 11q13 in non
      melanoma skin cancer.
AB  - Deregulation of the cell-cycle G1-restriction point control via abnormalities of
      Rb-pathway components is a frequent event in the formation of cancer. The aim of
      this study was to evaluate numerical aberrations of the Cyclin D1 (CCND1, PRAD1,
      bcl-1) gene locus at chromosome 11q13 in basal cell carcinomas (BCCs) and
      squamous cell carcinomas (SCCs) of the skin and to compare it with the Cyclin D1
      protein expression. Fluorescence in situ hybridization with DNA-probes specific
      for the Cyclin D1 gene locus and the centromere of chromosome 11 as well as
      immunostaining for Cyclin D1 protein was applied on 5 microm serial paraffin
      sections. Six of the 30 (20%) SCCs showed additional Cyclin D1 gene copies and
      2/30 (6.6%) cases had a loss of the Cyclin D1 gene locus in relation to the
      centromere 11 number. In contrast, only one of the 14 BCCs (7%) showed one
      additional Cyclin D1 gene copy in relation to the centromere 11 number. None of
      the BCCs demonstrated aneusomy for chromosome 11 in contrast to SCCs, where it
      was found in 21/30 (70%) cases. Twenty-six of the 30 (86.6%) cutaneous SCCs and
      13/14 (93%) BCCs expressed Cyclin D1 protein. All SCCs and the BCC with
      additional Cyclin D1 gene copies showed positivity for Cyclin D1 protein. Both
      SCCs with less Cyclin D1 gene copies than centromere 11 signals showed a weak
      protein expression. Our findings suggest that numerical abnormalities of the
      Cyclin D1 gene locus could result in an altered gene-dose effect, possibly
      leading to an aberrant expression in affected tumor cells. This might result in
      deregulation of cell cycle control, eventually leading to uncontrolled cell cycle
      progression.

PMID- 15723721
TI  - Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via
      its receptor, TNFR2.
AB  - We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line,
      CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with
      TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn
      activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness
      of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited
      the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked
      invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin,
      suppressed the invasion in a dose-dependent manner. Similarly, pharmacological
      inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9
      secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an
      important role to convert the cholangiocarcinoma cells to be more aggressive one.

PMID- 15723722
TI  - Enhanced antitumor activity of xanthohumol, a diacylglycerol acyltransferase
      inhibitor, under hypoxia.
AB  - Cancer chemotherapy for hypoxic tumor cells is thought to be an important issue,
      since hypoxia is related to tumor growth, apoptosis, angiogenesis and metastasis.
      Here, the bioactivities of xanthohumol (XN), a diacylglycerol acyltransferase
      inhibitor, against hypoxic cells were investigated. At first, the inhibitory
      effects of XN on the formation of lipid droplets in the cytoplasm were evaluated
      in hypoxia. Hypoxia upregulated the synthesis of triglyceride and promoted the
      formation of lipid droplets in the cytoplasm, however, the treatment of XN
      downregulated the triglyceride synthesis and completely canceled the appearance
      of lipid droplets. Second, the effects of XN on the proliferation and the
      motility of HT-1080 human fibrosarcoma were investigated. The proliferation of HT
      1080 was significantly suppressed in the presence of XN only in hypoxic condition
      but not in normoxic condition. XN also suppressed the motility of HT-1080 that
      was enhanced by hypoxia. Since, most cells in solid tumor were thought to be in
      hypoxic condition and acquired malignancy in response to hypoxia, these data
      suggest that XN may have potent and specific activities against cancerous cells.
      Furthermore, these data suggested that lipid metabolism may play an important
      role for hypoxic tumor cells and proposed a new therapeutic target for cancer
      chemotherapy.

PMID- 15723723
TI  - Expression of cancer/testis (CT) antigens in Chinese hepatocellular carcinoma and
      its correlation with clinical parameters.
AB  - For investigating the expression of cancer/testis (CT) antigens in patients with
      hepatocellular carcinoma (HCC) in China, and evaluating the correlations between
      the expression of these CT antigens and clinical parameters, we collected tumors
      and adjacent non-cancerous tissues of 43 HCC patients from Beijing and 30 HCC
      patients from Guangxi province. Expression of the mRNA of 14 CT antigens was
      evaluated by reverse transcription PCR (RT-PCR). The correlation between CT
      antigen expression and clinical parameters was statistically analyzed. The mRNA
      expression frequencies of CT antigens in tumor tissue were: MAGE-A1, 69.9%; MAGE
      A3, 47.9%; MAGE-A4, 20.0%; MAGE-A10, 36.7%; SSX-1, 67.4%; SSX-2, 35.6%; SSX-4,
      48.8%; SSX-5, 30.2%; NY-ESO-1, 42.5%; MAGE-B1, 52.0%; MAGE-B2, 60.0%; MAGE-C1,
      48.0%; MAGE-C2, 68.0%; and SCP-1, 33.3%. However, in adjacent tissues, no CT
      antigen mRNA expression was detected, except SSX-1 in 9.3% patients. In each HCC
      tissue, the expression of a minimum of one, two, or three CT antigens was in the
      range of 80-90, 70-80 or 50-70%, respectively. MAGE-A3 mRNA expression differed
      between the HCC patients in Beijing and Guangxi (P=0.002). The average age of the
      HCC patients bearing CT antigen positive tumors was higher than that of the HCC
      patients bearing CT antigen negative tumors. The expression of MAGE-A3, SSX-1,
      SSX-2, SSX-4, MAGE-B2, MAGE-C1, and MAGE-C2 correlated significantly with older
      age (P<0.05). Moreover, the expressions of MAGE-A4 and SCP-1 were related to
      alpha-fetoprotein abnormality (P<0.05), and the expression of NY-ESO-1 was
      related to early tumor stage (P<0.05). There was no correlation observed between
      the expression of CT antigens and the sex, HBV infection or tumor size.

PMID- 15723724
TI  - HPA binding and metastasis formation of human breast cancer cell lines
      transplanted into severe combined immunodeficient (scid) mice.
AB  - Six human breast cancer cell lines were injected subcutaneously into scid mice
      and their in vivo growth behaviour and HPA binding pattern were analysed.
      Furthermore, the role of HPA binding glycoconjugates concerning the adhesion to
      endothelial cells in vitro was investigated. Four of the tested cell lines
      engrafted in the scid mouse model but they showed considerable variations
      concerning their growth behaviour, their metastatic potential and their HPA
      binding pattern. HPA inhibited adhesive interactions between cell lines derived
      from metatstatic sources and tumour necrosis factor (TNF)alpha stimulated
      endothelial cells. The transplantation of HPA defined breast cancer cell lines
      into scid mice is a useful animal model for the research of breast cancer and its
      metastasis. The HPA binding glycoconjugates appear to be associated with adhesive
      interactions between metastasising tumour cells and endothelial cells.

PMID- 15723725
TI  - Medications work for severely addicted smokers: implications for addiction
      therapists and primary care physicians.

PMID- 15723726
TI  - Substance abuse treatment and risk behaviors among HIV-infected persons with
      alcohol problems.
AB  - We examined the association of substance abuse treatment with sexual and drug use
      risk behaviors among 349 HIV-infected persons with a history of alcohol problems
      using a standardized questionnaire regarding sexual and drug use risk behaviors,
      demographics, substance use, and use of substance abuse treatment. We defined
      substance abuse treatment services as any of the following in the past 6 months:
      12 weeks in a half-way house or residential facility; 12 visits to a substance
      abuse counselor or mental health professional; day treatment for at least 30
      days; or participation in any methadone maintenance program. Our three outcome
      variables of high-risk behavior were the Risk Assessment Battery sex-risk and
      drug-risk scores and high-risk sex behavior which included any of the following:
      inconsistent condom use; having more than one sexual partner; and exchanging sex
      for money or drugs. Although sexual risk was high (51%) in our HIV-infected
      cohort, engagement in substance abuse treatment was not independently associated
      with lower frequency of any of our measures of high- risk behaviors. Although the
      opportunity exists to address HIV risk behaviors in the setting of substance
      abuse treatment, effective institutionalization of this challenging behavior
      change effort has not yet been realized.

PMID- 15723727
TI  - Practice variation and length of stay in alcohol and drug detoxification centers.
AB  - Admissions to 20 publicly funded alcohol and drug detoxification centers in
      Massachusetts were examined to identify program and patient variables that
      influenced length of stay. The last admission during fiscal year 1996 was
      abstracted for patients 18 years of age and older seeking alcohol, cocaine, or
      heroin detoxification (n=21,311; 29% women). A hierarchical generalized linear
      model examined the effects of patient and program characteristics on variation in
      length of stay and tested case-mix adjustments. Program size had the most
      influence on mean adjusted length of stay; stays were more than 40% longer in
      detoxification centers with 35 or more beds (7.69 days) than in centers with less
      than 35 beds (5.42 days). The study highlights the contribution of program size
      to treatment processes and suggests the need for more attention to program
      attributes in studies of patient outcomes and treatment processes.

PMID- 15723728
TI  - Assessing competence in the use of motivational interviewing.
AB  - This report presents reliability, validity and sensitivity indices for the
      Motivational Interviewing Treatment Integrity (MITI) scale. Factor analysis of MI
      treatment sessions coded with the Motivational Interviewing Skills Code (MISC)
      was used to derive 10 elements of MI practice, forming the MITI. Canonical
      correlation revealed that the MITI captured 59% of the variability in the MISC.
      Reliability estimates for the MITI were derived using three masked, independent
      coders. Intra-class coefficients ranged from .5 to .9 and were generally in the
      good to excellent range. Comparison of MITI scores before and after MI workshops
      indicate good sensitivity for detecting improvement in clinical practice as
      result of training. Implications for the use of this instrument in research and
      supervision are discussed.

PMID- 15723729
TI  - Absenteeism and business costs: does substance abuse matter?
AB  - We conducted an empirical test of the assertion that absenteeism related to
      substance abuse and dependence among workers is an important contributor to the
      cost of doing business among American companies, a cost sufficient to motivate
      firms to aggressively intervene to eliminate abuse and dependence among their
      employees. The results of this analysis, based on relevant national data sets,
      suggest that such abuse-based absenteeism is, at best, an incidental cost to
      business and is insufficient to justify significant prophylactic or therapeutic
      investments of scarce human resource dollars to achieve an abuse and dependence
      free workplace. These findings force both public and private sector policymakers
      to turn to a "hazardous use"/"critical incident" rational as the basis of their
      argument that American business should invest human resource dollars in specific
      programs and technologies designed to achieve a drug-free workplace.

PMID- 15723730
TI  - The impact of illicit drug market changes on health agency operations in Sydney,
      Australia.
AB  - At the end of 2000, in Sydney, Australia, there was a dramatic reduction in
      heroin availability. This study examines how health agencies treating clients for
      drug and alcohol related issues were able to respond to the changes that took
      place in their clients and their treatment needs. Key informant interviews were
      conducted with 48 staff from a wide range of health services in Sydney to provide
      the data for a thematic analysis. Changes experienced by health agencies included
      changed patterns of drug use in their clients, increased aggressive incidents,
      changed numbers of clients accessing treatment services, and a need for more
      assistance from outside agencies. A strong evidence base for a range of drug
      treatment options, support of staff development in aggression management skills,
      and development of good interagency links between mental health, drug and
      alcohol, and law enforcement services would make health services better prepared
      for future changes in the drug use of their clients.

PMID- 15723731
TI  - Patient reaction to traumatic injury and inpatient AODA consult: six-month follow
      up.
AB  - This paper describes the effects of traumatic injury and an inpatient Alcohol and
      Other Drug Abuse consultation on patients admitted to a university hospital with
      a positive blood alcohol concentration. Forty-six subjects reported 6-month post
      injury data on their alcohol use and treatment, referral compliance, injuries,
      health care utilization, motor vehicle events, and quality of life. Sixty-one
      percent reported abstinence in the previous 7 days and no binge consumption in
      the previous 30 days. Fifty percent met criteria for current depression. The
      sample accounted for significant post-discharge health care utilization including
      206 outpatient visits and five additional hospitalizations. Thirteen percent were
      still receiving disability compensation and 44% missed at least 1 day of work in
      the last 30 days due to their injuries. The 46 subjects reported a lifetime
      incidence of 72 alcohol-related injuries, 74 motor vehicle crashes, and 88 other
      legal events.

PMID- 15723732
TI  - The effectiveness of nicotine patch and nicotine lozenge in very heavy smokers.
AB  - The efficacy of nicotine replacement therapy (NRT) among very heavy and highly
      dependent smokers was examined in a secondary analysis of two randomized clinical
      trials of NRT. In the first trial, smokers were assigned to active patch (n=249)
      or placebo (n=253) plus intensive behavioral treatment. In the second trial,
      smokers were assigned to active 4-mg nicotine lozenge (n=450) or placebo (n=451)
      plus brief behavioral treatment. Nicotine patch and lozenge significantly
      increased 6-month continuous abstinence quit rates in both very heavy (>or=40
      cigarettes per day) and highly dependent (Fagerstrom Tolerance Questionnaire or
      Fagerstrom Test for Nicotine Dependence score >7) smokers. The effect of active
      NRT treatment did not differ significantly by smoking rate or nicotine
      dependence, with the exception that the nicotine patch was significantly more
      effective than placebo in highly dependent smokers. The nicotine patch and
      lozenge are effective (vs. placebo) even in heavy and highly dependent smokers.

PMID- 15723733
TI  - Something of value: the introduction of contingency management interventions into
      the New York City Health and Hospital Addiction Treatment Service.
AB  - This paper explores the impact of the adoption of the contingency management
      approach by the Chemical Dependency Treatment Services of the New York City
      Health and Hospitals Corporation (HHC). The utilization of this approach grew out
      of an alliance between NIDA Clinical Trials Network-affiliated clinicians and
      researchers and a leadership team at the HHC. Interviews and dialogues with
      administrators, staff, and patients revealed a shared sense that the use of
      contingency management had: (1) increased patient motivation for treatment and
      recovery; (2) facilitated therapeutic progress and goal attainment; (3) improved
      the attitude and morale of many staff members and administrators; and (4)
      developed a more collegial and affirming relationship not only between patients
      and staff, but also among staff members.

PMID- 15723734
TI  - Private insurance and the utilization of chemical dependency treatment.
AB  - This study examines how different types of health coverage influence the
      likelihood of entering treatment for an alcohol problem, and the extent that
      people in treatment are able to use their insurance to help cover the costs of
      care. Survey data are analyzed from a sample of problem drinkers drawn from the
      general population and chemical dependency treatment programs in the same
      community. We find that, in comparison to being on Medicaid and being uninsured,
      having private coverage does not significantly alter the odds of treatment entry.
      Being in a private managed care plan, as compared to traditional indemnity
      coverage, also does not appear to impact the chances of treatment entry. However,
      having private coverage, as compared to being on Medicare, doubles the odds of
      treatment entry. For problem drinkers who obtain treatment, those with private
      coverage are as or more likely than other insured groups to report that insurance
      helped to pay treatment expenses. Even so, 10% of those privately insured report
      having paid for all of their treatment costs out of pocket. We conclude that,
      while prior studies have rarely found that having insurance significantly impacts
      alcohol treatment entry, the type of coverage one possesses may matter in some
      cases. Our results concerning Medicare coverage may point to potential problems
      with making treatment affordable to some problem drinkers outside the private
      insurance system.

PMID- 15723735
TI  - Treatment outcomes among women and men methamphetamine abusers in California.
AB  - This prospective longitudinal study examined treatment outcomes among 1,073
      methamphetamine-abusing patients (567 women, 506 men) from 32 community-based
      outpatient and residential programs in 13 California counties. Data were
      collected at intake and at 3 months and 9 months after admission. With one
      exception, improvements from baseline to follow-up were observed in all areas
      measured by the Addiction Severity Index for both women and men in either
      modality. Compared to men, women demonstrated greater improvement in family
      relationships and medical problems, and similar improvement in all other areas,
      despite the fact that more women were unemployed, had childcare responsibilities,
      were living with someone who also used alcohol or drugs, had been physically or
      sexually abused, and reported more psychiatric symptoms. Implications for service
      improvement are discussed.

PMID- 15723736
TI  - Comparison between handgrip strength, subjective global assessment, and
      prognostic nutritional index in assessing malnutrition and predicting clinical
      outcome in cirrhotic outpatients.
AB  - OBJECTIVE: This study compared three methods of assessing malnutrition in
      cirrhotics and correlated nutritional status with clinical outcome. METHODS: This
      cross-sectional study evaluated nutritional status by subjective global
      assessment (SGA), prognostic nutritional index (PNI), and handgrip strength (HG)
      in outpatients with cirrhosis (n = 50) and two control groups with hypertension
      (n = 46) and functional gastrointestinal disorders (n = 49). Patients with
      cirrhosis were followed for 1 y to verify the incidence of major complications,
      the need for transplantation, and death. RESULTS: Among patients with cirrhosis,
      88% were Child-Pugh A and only 12% were Child-Pugh B. Among these, prevalences of
      malnutrition were 28% by SGA, 18.7% by PNI, and 63% by HG (P < 0.05). HG, but not
      SGA or PNI, predicted a poorer clinical outcome in patients with cirrhosis
      because major complications such as uncontrolled ascites, hepatic encephalopathy,
      spontaneous bacterial peritonitis, and hepatorenal syndrome developed in 65.5% of
      malnourished patients versus 11.8% of well-nourished ones (P < 0.05). No
      significant differences by any method were seen between the two groups regarding
      liver transplantation or death. CONCLUSIONS: There was a high prevalence of
      malnutrition in cirrhotic outpatients, especially when assessed by HG, which was
      superior to SGA and PNI in this study. HG was the only technique that predicted a
      significant incidence of major complications in 1 y in undernourished cirrhotic
      patients.

PMID- 15723737
TI  - Dynamics of antioxidants in patients with acute pancreatitis and in patients
      operated for colorectal cancer: a clinical study.
AB  - OBJECTIVES: This clinical study compared the dynamics of antioxidants levels in
      patients with acute pancreatitis (AP), patients operated for colorectal cancer
      (CA), and healthy control subjects. METHODS: This prospective descriptive study
      enrolled 21 AP and 14 CA patients and 17 healthy controls. Blood was collected
      from AP patients on days 1, 5, and 9 and from CA patients before surgery and on
      days 1, 5, and 9 after surgery. We measured concentrations of selenium in plasma,
      red blood cells (RBCs), and big-toe nails, vitamin A (retinol) in serum, alpha
      tocopherol in serum and in RBCs, vitamin C in serum, concentration ratio of 9,11-
      and 10,12-octadecanoic acids to linoleic acid in RBC membrane, activity of
      superoxide dismutase, and glutathione peroxidase in RBCs. RESULTS: Plasma
      concentrations of selenium, vitamin A, and vitamin C were significantly lower in
      AP and CA patients than in healthy controls over the monitored period (P < 0.05).
      Patients with severe AP had a significantly lower concentration of selenium in
      RBCs than did healthy controls and CA patients (P < 0.05). The concentration of
      selenium in toe nails of AP patients was significantly lower than that in CA
      patients and healthy controls (P < 0.001). The marker of increased reactive
      oxygen species activity the ratio of 9,11- and 10,12-octadecanoic acids to
      linoleic acid in RBCs was significantly higher in AP and CA patients than in
      healthy controls (P < 0.05). CONCLUSIONS: Low levels of measured antioxidants and
      increased activity of reactive oxygen species occurred during the course of AP.
      These findings applied in particular to patients who had severe AP. Levels of
      measured antioxidants seemed to be similar in AP and CA patients except for lower
      levels of selenium in toe nails in AP patients and lower selenium concentrations
      in RBCs in patients with severe AP.

PMID- 15723738
TI  - Association between dietary arginine and C-reactive protein.
AB  - OBJECTIVE: We investigated whether a dietary intake of arginine is associated
      with risk for cardiovascular disease as determined by levels of C-reactive
      protein (CRP). METHODS: We analyzed the Third National Health Nutrition and
      Examination Survey, a national public-use dataset collected between 1988 and
      1994. Arginine intake was calculated from the 24-h dietary recall using the
      nutrient composition database of the University of Minnesota Nutrition
      Coordinating Center. A logistic regression model was used to evaluate the
      relation between arginine intake and serum levels of CRP while controlling for
      age, sex, race, exercise, total caloric intake, body mass index, smoking status,
      diabetes, hypertension, and fiber intake. RESULTS: In the unadjusted model, the
      likelihoods of having a high level of CRP (>3.0 mg/L), from the lowest to the
      highest level of arginine intake, were 34.8%, 31.0%, 27.7%, and 18.4%
      respectively. Arginine intake below the median range was associated with higher
      levels of CRP (P < 0.05), and arginine intake above the median range was
      associated with lower levels of CRP (P < 0.05). In the adjusted regression,
      subjects in the highest level (90th percentile) of arginine intake were 30% less
      likely to have a CRP above 3.0 mg/L than were subjects with a median arginine
      intake (odds ratio= 0.70, 95% confidence interval = 0.56 to 0.88). CONCLUSIONS:
      The results of this study show a relation between arginine intake and CRP level
      that persisted after controlling for factors associated with CRP. Individuals may
      be able to lower their risk for cardiovascular disease by consuming more arginine
      rich foods such as nuts and fish.

PMID- 15723739
TI  - Supplementation of fish oil and olive oil in patients with rheumatoid arthritis.
AB  - OBJECTIVE: This study evaluated whether supplementation with olive oil could
      improve clinical and laboratory parameters of disease activity in patients who
      had rheumatoid arthritis and were using fish oil supplements. METHODS: Forty
      three patients (34 female, 9 male; mean age = 49 +/- 19y) were investigated in a
      parallel randomized design. Patients were assigned to one of three groups. In
      addition to their usual medication, the first group (G1) received placebo (soy
      oil), the second group (G2) received fish oil omega-3 fatty acids (3 g/d), and
      the third group (G3) received fish oil omega-3 fatty acids (3 g/d) and 9.6 mL of
      olive oil. Disease activity was measured by clinical and laboratory indicators at
      the beginning of the study and after 12 and 24 wk. Patients' satisfaction in
      activities of daily living was also measured. RESULTS: There was a statistically
      significant improvement (P < 0.05) in G2 and G3 in relation to G1 with respect to
      joint pain intensity, right and left handgrip strength after 12 and 24 wk,
      duration of morning stiffness, onset of fatigue, Ritchie's articular index for
      pain joints after 24 wk, ability to bend down to pick up clothing from the floor,
      and getting in and out of a car after 24 wk. G3, but not G2, in relation to G1
      showed additional improvements with respect to duration of morning stiffness
      after 12 wk, patient global assessment after 12 and 24 wk, ability to turn
      faucets on and off after 24 wk, and rheumatoid factor after 24 wk. In addition,
      G3 showed a significant improvement in patient global assessment in relation to
      G2 after 12 wk. CONCLUSIONS: Ingestion of fish oil omega-3 fatty acids relieved
      several clinical parameters used in the present study. However, patients showed a
      more precocious and accentuated improvement when fish oil supplements were used
      in combination with olive oil.

PMID- 15723740
TI  - Serum folate and homocysteine levels in obese females with non-alcoholic fatty
      liver.
AB  - OBJECTIVE: Folate depletion and hyperhomocysteinemia increase the risk for
      hepatic alcoholic damage and promote oxidative stress in animals. In addition,
      some investigators have reported an inverse association between serum folate and
      body mass index and a positive correlation between total homocysteine and fat
      mass. We investigated whether there is an association between serum folate and
      total homocysteine concentrations with the presence of non-alcoholic fatty liver
      disease (NAFLD) in obese subjects. METHODS: Forty-three obese (body mass index >
      or =35 kg/m2) patients who underwent bariatric surgery and hepatic biopsy were
      included. Serum total homocyteine, folate and vitamin B12 concentrations and
      hepatic enzymes were measured. Liver biopsies were graded for the presence of
      fat, inflammation, and fibrosis on a scale from 0 to 3. A total histologic score
      was calculated based on the sum of partial scores. Severe NAFLD was defined as a
      total score of at least 4 or severe steatosis (partial score for fat = 3).
      RESULTS: Severe NAFLD was present in 17 patients. Serum folate concentration was
      significantly lower in obese patients with NAFLD than in those with normal liver
      or minimal alterations (9.3 +/- 3.5 versus 12.2 +/- 3.1 ng/mL, P = 0.005). Serum
      total homocysteine and vitamin B12 concentrations were similar in both groups. An
      inverse correlation between serum folate concentration and body mass index was
      observed (r = -0.31, P = 0.046). CONCLUSIONS: In this study, severe NAFLD in
      obese subjects was associated with lower serum folate concentrations and serum
      homocysteine and vitamin B12 concentrations were not associated with liver damage
      in obese subjects.

PMID- 15723741
TI  - Early enteral feeding in newborn surgical patients.
AB  - OBJECTIVE: We report the results of a multicenter prospective trial of early
      enteral trophic feeding in a group of 56 neonates who required abdominal surgery
      for a variety of congenital anomalies. METHODS: In this clinical study, 33
      neonates were fed in the early postoperative period (early enteral nutrition
      [EEN] group), and the remaining 23 (control [C] group) were fasted until
      resolution of postoperative ileus. Patients in the EEN group (Kocaeli feeding
      protocol) received 3 to 5 mL of breast milk every hour through a nasogastric
      feeding tube, starting a mean of 12 h (8 to 20 h) after surgery. The nasogastric
      tube was clamped for 40 min after each infusion and then opened for drainage.
      Groups were further divided into two subgroups according to whether an intestinal
      anastomosis or laparotomy was performed. The change in daily gastric drainage,
      time to first stool, day of toleration to full oral feeding, and length of
      hospital stay were compared. Blood bilirubin levels, white blood cell count, and
      C-reactive protein levels were monitored. RESULTS: The time to first stool and
      day of toleration to full oral feeding occurred significantly sooner, whereas
      nasogastric tube drainage duration and hospital stay were significantly shorter
      in the EEN-anastomosis group than in the C-anastomosis group. Time to first stool
      occurred significantly sooner in the EEN-laparotomy group than in the C
      laparotomy group, although other parameters did not differ. Neither anastomotic
      leakage nor dehiscence was observed in any group. There were two cases of wound
      infection and two of exitus among patients in the C group. CONCLUSION:
      Postoperative, early intragastric, small-volume breast milk feeding is well
      tolerated by newborns. It is a reliable and feasible approach in neonates even in
      the presence of an intestinal anastomosis after abdominal surgery.

PMID- 15723742
TI  - Effect of nutritional supplements on wound healing in home-nursed elderly: a
      randomized trial.
AB  - OBJECTIVE: The objective was to determine whether provision of oral nutritional
      supplements, delivered by community nurses, could improve nutritional status and
      wound healing in home-nursed elderly. METHODS: This was a double-blind,
      randomized trial in 50 elderly patients referred for wound management. Patients
      received 237 mL/d of 4 or 8 kJ/mL of an oral nutritional supplement for 4 wk.
      Nutritional status was measured with the Subjective Global Assessment and the
      Mini-Mental State Examination questionnaire to determine cognitive function and
      wound characteristics to assess healing. Differences between variables were
      examined with the Mann-Whitney or Student's t test for comparing two groups, one
      way analysis of variance when there was more than two groups, and chi-square
      analysis for comparing two categorical variables. Associations between variables
      were examined with Pearson's correlation and regression analysis. RESULTS: At
      baseline, 34% subjects were moderately malnourished and 8% were severely
      malnourished. In both groups, there was significantly greater improvement in Mini
      Mental State Examination scores at week 4 (95% confidence interval -2.0 to 
      0.001, P = 0.04) and a greater decrease in the wound effusion score (95%
      confidence interval -2.0 to 0.0, P = 0.045). Median length of stay did not differ
      between groups (P > 0.05). CONCLUSIONS: Malnutrition is common in elderly
      patients who are nursed at home for wound management. Provision of energy- and
      protein-dense oral supplements by community nurses is effective in improving some
      indices of wound healing and cognitive function in this group. Although further
      study is needed to determine the effect on length of stay, the nutritional needs
      of this vulnerable group should not be overlooked.

PMID- 15723743
TI  - Home parenteral nutrition registry: a five-year retrospective evaluation of
      outcomes of patients receiving home parenteral nutrition support.
AB  - OBJECTIVE: Few data are currently reported on home parenteral nutrition (HPN)
      patient outcomes, which makes evaluating comparative outcomes in HPN difficult.
      This study describes outcomes of consecutive HPN patients collected
      retrospectively over a 5-y period by one HPN support provider. METHODS:
      Retrospective data from the HPN support provider was aggregated yearly from 1997
      to 2001. Length of therapy, demographics, diagnosis, rehospitalizations, catheter
      infection rate, catheter occlusion rate, and mechanical complication rate data
      were reported. RESULTS: The mean age of HPN patients ranged from 42 y to 45 y.
      The average length of HPN therapy was 100 d. There were more female than male HPN
      patients. Nutritional deficiency and malabsorption were the most common
      International Classification of Diseases, Ninth Revision codes for HPN use and
      reflects a focus on nutritional diagnosis rather than on disease state as the
      criterion for HPN use. Catheter infection rates ranged from 0.44 to 0.84 per 1000
      catheter days, a lower than anticipated number. Mean catheter occlusion rates
      were lower than 7% and mean mechanical complication rates were approximately 5%.
      Known termination of therapy was secondary to completion of therapy (50% to 56%)
      or death (17.3% to 22%). CONCLUSIONS: Overall, time on HPN therapy in the United
      States has increased. Nutritional diagnoses are currently used to justify HPN.
      Catheter infection and occlusion rates, in general, are low. Termination of
      therapy and death are the most common reasons for HPN discontinuation.
      Standardization of HPN data collection is necessary to obtain a historical
      snapshot of the efficacy and safety of patients treated outside the hospital with
      nutritional support.

PMID- 15723744
TI  - Comparison of fat-free mass and body fat in Swiss and American adults.
AB  - OBJECTIVE: No current studies have compared North American with European body
      composition parameters, i.e., fat-free mass (FFM), body fat (BF), and percentage
      of BF (%BF) in large populations. This study compared FFM, BF, and %BF values
      derived from two bioelectrical impedance analysis (BIA) equations (Geneva and
      National Health and Nutrition Examination Survey [NHANES]) in Swiss subjects and
      compared FFM, BF, and %BF values of white Swiss with those of white North
      American adults with the same BIA equations. METHODS: Healthy adults (3714 men
      and 3199 women), ages 20 to 79 y, in Switzerland were measured by single
      frequency BIA and compared with means and standard deviations for body mass index
      and body composition parameters obtained from the NHANES III study (United
      States; n = 2538 men, 2862 women). FFM was calculated with the Geneva and NHANES
      equations. RESULTS: Mean FFMGENEVA values did not differ from FFMNHANES values in
      men but was significantly lower (-1.5 kg) in women. FFM and BF values in American
      men, who weighed 4.2 to 12.0 kg more than the Swiss men, were significantly
      higher (+2.1 to +6.0 kg and +1.5 to +6.4 kg, respectively) than those in the
      Swiss men. FFM and BF values in American women, who weighed 2.3 to 12.1 kg more
      than the Swiss women, were significantly higher (+1.3 to +2.1 kg and +4.8 to
      +11.8 kg, respectively, except FFM in subjects ages 20 to 29 y and BF in those
      ages 70 to 79 y) than FFMGENEVA values in Swiss women. FFM in American women was
      significantly lower (+1.3 and +1.9 kg) and non-significantly higher than
      FFMNHANES in Swiss women. CONCLUSION: NHANES and Geneva BIA equations estimate
      body composition equally well in men, but further research is necessary to
      determine the discrepancies in FFM between BIA equations in women. The greater
      weight of the American subjects yielded higher values for FFM, BF, and %BF in
      American than in Swiss men and women.

PMID- 15723745
TI  - Impact of fish oil and melatonin on cachexia in patients with advanced
      gastrointestinal cancer: a randomized pilot study.
AB  - OBJECTIVE: The effect of fish oil (FO), melatonin (MLT), or their combination and
      dietary advice on cachexia and biochemistry variables reflecting cachexia were
      investigated in patients with advanced gastrointestinal cancer. METHODS: Twenty
      four patients not amenable to standard anticancer treatment and with documented
      weight loss and/or decreased serum albumin were included. They were randomized to
      30 mL/d of FO, which provided 4.9 g of eicosapentaenoic acid and 3.2 g of
      docosahexanoic acid, or 18 mg/d of MLT for 4 wk. During the next 4 wk, all
      patients had FO and MLT. Serum or plasma was analyzed for tumor necrosis factor
      alpha, interleukin-1beta, soluble interleukin-2 receptor, interleukin-6, and
      interleukin-8 and the fatty acids eicosapentaenoic acid, docosahexanoic acid,
      arachidonic acid, and linoleic acid. RESULTS: Serum levels of eicosapentaenoic
      acid and docosahexanoic acid increased as expected with FO. No major changes in
      biochemical variables and cytokines were observed with any intervention. In the
      FO group, 5 of 13 patients (38%) showed weight stabilization or gain compared
      with 3 of 11 patients (27%) in the MLT group. After combining interventions,
      approximately 63% of patients showed such responses. CONCLUSIONS: FO, MLT, or
      their combination did not induce major biochemical changes indicative of a strong
      anticachectic effect. Nonetheless, the interventions used may have produced a
      weight-stabilizing effect.

PMID- 15723746
TI  - Effect of lean system 7 on metabolic rate and body composition.
AB  - OBJECTIVE: This study evaluated whether a commercial weight-loss product (Lean
      System 7) would result in less reduction in resting metabolic rate (RMR) in
      overweight subjects on a calorie-restricted diet and exercise regimen than in
      subjects using diet and exercise alone. METHODS: In this randomized, double
      blind, placebo-controlled study, healthy overweight adults were given three
      capsules of a commercial weight-loss product twice daily or an identical placebo
      and followed a calorie-restricted diet and an exercise program for 8 wk. RMR,
      body weight, body mass index, waist and hip circumferences, and body composition
      by dual-energy x-ray absorptiometry were measured at baseline and week 8. An
      intention-to-treat analysis was performed. RESULTS: Of 47 adults enrolled, 35
      completed the study. Subjects taking the commercial weight-loss product had a
      significant (P = 0.03) increase in RMR, 7.2% increase versus 0.7% decrease in the
      placebo group. Subjects taking the commercial weight-loss product also had a
      significant (P = 0.04) decrease in hip circumference, 3.78 cm versus 2.07 cm in
      the placebo group. There were no other statistically significant differences in
      any other outcome variable, diet composition, exercise compliance, or adverse
      events. CONCLUSION: The results of this study showed that administration of a
      commercial weight-loss product to overweight adults in conjunction with a calorie
      restricted diet and moderate exercise program effectively reverses the decrease
      in RMR associated with calorie restriction within this study population. The
      commercial weight-loss product was well tolerated, and there were no serious
      adverse events over the 8 wk studied.

PMID- 15723747
TI  - Gestational hyperglycemia, zinc, selenium, and antioxidant vitamins.
AB  - OBJECTIVE: Lower levels of selenium and vitamin E have been described in
      gestational diabetes, a condition similar to type 2 diabetes, but few data are
      available about zinc (known to be associated with diabetes) and gestational
      hyperglycemia. This study evaluated the dietary intake of antioxidant vitamins,
      zinc, selenium, and serum levels of zinc and selenium in women with gestational
      hyperglycemia and normoglycemia. METHODS: A food-frequency questionnaire was
      administered to 504 pregnant women (210 with hyperglycemia and 294 with
      normoglycemia). Serum levels of zinc and selenium were analyzed during pregnancy
      in a second cohort of 71 hyperglycemic and 123 normoglycemic women, with a mean
      age and body mass index similar to those in the first cohort. RESULTS: Dietary
      intakes of zinc and selenium were significantly lower in hyperglycemic patients.
      In multiple logistic regression analysis, intakes were negatively associated with
      gestational hyperglycemia (odds ratios of 0.89 for zinc and 0.97 for selenium)
      after multiple adjustments. There were no significant differences in vitamin
      intakes. In the second cohort of 194 patients, serum levels of zinc and selenium
      were significantly lower in patients who had impaired glucose tolerance and
      negatively associated with gestational hyperglycemia in a multiple logistic
      regression model (odds ratios of 0.93 for serum zinc and 0.92 for serum
      selenium). CONCLUSIONS: Our data suggested a significant inverse association of
      dietary intakes and serum levels of zinc and selenium with gestational
      hyperglycemia. If future studies confirm these results, it might be a useful
      interventional approach to appropriate dietary counseling in order to evaluate
      the possible decrease in gestational metabolic abnormalities and their adverse
      consequences.

PMID- 15723748
TI  - Adequate feeding and the usefulness of the respiratory quotient in critically ill
      children.
AB  - OBJECTIVE: We determined incidences of underfeeding and overfeeding in children
      who were admitted to a multidisciplinary tertiary pediatric intensive care and
      evaluated the usefulness of the respiratory quotient (RQ) obtained from indirect
      calorimetry to assess feeding adequacy. METHODS: Children 18 y and younger who
      fulfilled the criteria for indirect calorimetry entered our prospective,
      observational study and were studied until day 14. Actual energy intake was
      recorded, compared with required energy intake (measured energy expenditure plus
      10%), and classified as underfeeding (<90% of required), adequate feeding (90% to
      110% of required), or overfeeding (>110% of required). We also evaluated the
      adequacy of a measured RQ lower than 0.85 to identify underfeeding, and an RQ
      higher than 1.0 to identify overfeeding. RESULTS: Ninety-eight children underwent
      195 calorimetric measurements. Underfeeding, adequate feeding, and overfeeding
      occurred on 21%, 10%, and 69% of days, respectively. An RQ lower than 0.85 to
      identify underfeeding showed low sensitivity (63%), high specificity (89%), and
      high negative predictive value (90%). An RQ higher than 1.0 to indicate
      overfeeding showed poor sensitivity (21%), but a high specificity (97%) and a
      high positive predictive value (93%). Food composition, notably high-carbohydrate
      intake, was responsible for an RQ exceeding 1.0 in the overfed group. CONCLUSION:
      Children admitted to the intensive care unit receive adequate feeding on only 10%
      of measurement days during the first 2 wk of admission. The usefulness of RQ to
      monitor feeding adequacy is limited to identifying (carbohydrate) overfeeding and
      excluding underfeeding.

PMID- 15723749
TI  - Inhibition of blood platelet adhesion and secretion by different phenolics from
      Yucca schidigera Roezl. bark.
AB  - OBJECTIVE: Yucca schidigera is a plant that grows in Mexico, and it has a very
      high level of saponins and phenolic compounds with antioxidant action. The
      products of Y. schidigera are used as food additives and have a generally
      recognized as safe label. This study investigated the antiplatelet mechanisms of
      four phenolic compounds. METHODS: We investigated antiplatelet mechanisms of the
      phenolic compounds trans-3,4',5-trihydroxystilbene (trans-resveratrol), trans
      3,3',5,5'-tetrahydroxy-4'-methoxystilbene, and yuccaols A and C that had been
      isolated from the bark of Y. schidigera by studying their effects on the first
      step of platelet activation, i.e., platelet adhesion to collagen and fibrinogen.
      The effects of these compounds on the release of adenine nucleotides, proteins,
      and beta-N-acetyl-glycosaminidase (a marker of lysosomal secretion) from blood
      platelets activated by thrombin were also studied. RESULTS: These different
      phenolic compounds (1 to 25 microg/mL) and their extracts decreased platelet
      adhesion and secretion. CONCLUSIONS: Resveratrol and yucca extract were more
      reactive in decreasing these processes than were other tested phenolic compounds.

PMID- 15723750
TI  - Plant genotype affects total antioxidant capacity and phenolic contents in fruit.
AB  - OBJECTIVE: We wanted to determine the total antioxidant capacity (6-hydroxy
      2,5,7,8-tetramethylchromane-2-carboxylic acid equivalent antioxidant assay; TEAC)
      of different species and cultivars (strawberry and apple) and to characterize the
      TEAC among fruits of the same varieties (peach and apricot) but grafted on
      different rootstocks. METHODS: The study was carried out with wild strawberry,
      six varieties of cultivated strawberry, and five varieties of apple and with
      apricot and peach grafted on five different rootstocks that are known to induce
      different plant vigor and fruit qualitative features. The TEAC (considering
      lipophilic and hydrophilic contributions) was determined for all fruit varieties,
      and total polyphenol contents were assayed. One-way analysis of variance was used
      to test differences among fruits and to identify possible correlations of TEAC
      versus total phenolics. RESULTS: The following hierarchy of antioxidant
      activities was found: wild strawberries >> cultivated strawberries >> kiwifruit =
      apples = apricots = peaches. Further, differences were found among strawberries
      with different genotypes and in apricots and peaches grafted from different
      rootstocks. CONCLUSIONS: These observations suggest the importance of genotype
      for determining antioxidant potential and phenolic contents. Variety manipulation
      may be a powerful tool for modifying antioxidant fruit patterns and contents.

PMID- 15723751
TI  - Glutamine attenuates endotoxin-induced lung metabolic dysfunction: potential role
      of enhanced heat shock protein 70.
AB  - OBJECTIVE: Septic shock leads to derangement of cellular metabolism. Enhanced
      heat shock protein 70 (HSP-70) can preserve cellular metabolism after other forms
      of cellular stress. Glutamine (GLN) can enhance lung HSP-70 expression after
      lethal endotoxemia. However, it is unknown whether GLN can enhance HSP-70
      expression and attenuate lung metabolic dysfunction after sublethal endotoxemia.
      Our aim was to determine whether GLN could upregulate HSP-70 and attenuate
      metabolic dysfunction in lung tissue after sublethal endotoxemia. METHODS:
      Sprague-Dawley rats were assigned to one of five groups. The first two groups
      were treated with Escherichia coli lipopolysaccharide (LPS; 1 mg/kg
      intravenously). GLN (0.75 g/kg intravenously) or balanced salt solution as a
      control was administered 5 min after LPS administration. The next two groups of
      rats were treated with quercetin (HSP-70 inhibitor; 400 mg/kg intraperitoneally)
      6 h before LPS administration. The final group received no treatment. Lung tissue
      was harvested 24-h after LPS and analyzed with immunofluorescence and western
      blot for HSP-70. Tissue metabolites were quantified by 1H and 31P nuclear
      magnetic resonance spectroscopy. RESULTS: GLN compared with balanced salt
      solution (BSS) administration in LPS-treated animals led to significant increases
      in lung HSP-70. Increased HSP-70 expression was observed in lung epithelial cells
      and macrophages. GLN significantly improved the ratio of adenosine triphosphate
      to adenosine diphosphate in the lung after LPS. Quercetin inhibited a GLN
      mediated increase in lung HSP-70 and blocked a beneficial effect of GLN on the
      ratio of adenosine triphosphate to adenosine diphosphate after LPS. CONCLUSIONS:
      A single dose of GLN can enhance HSP-70 in pulmonary epithelial cells and
      macrophages after sublethal endotoxemia. Further, GLN can attenuate endotoxin
      induced lung metabolic dysfunction. GLN's beneficial effect on lung tissue after
      metabolic dysfunction caused by sublethal endotoxemia may be mediated in part by
      enhanced HSP-70.

PMID- 15723752
TI  - Effect of diet supplementation with glutamine, dihydroxyacetone, and leucine on
      food intake, weight gain, and postprandial glycogen metabolism of rats.
AB  - OBJECTIVE: We tested the hypothesis that increasing the rate of postprandial
      hepatic glycogen synthesis would decrease food intake and growth rate in normal
      rats. METHODS: Diets supplemented with glutamine, glutamine plus
      dihydroxyacetone, and glutamine plus dihydroxyacetone plus leucine were
      administered to male Sprague-Dawley rats for 1 wk. These are combinations that
      have been shown to stimulate hepatic glycogen synthesis in vitro. Food intake and
      body weight were monitored throughout the experiment. At the end of the feeding
      period, rats were fed a test meal and injected with 3H2O to measure in vivo rates
      of glycogen and lipid synthesis. Positional analysis of the 3H incorporated into
      glycogen was used to determine the proportion of glycogen synthesized via
      pyruvate. Final levels of plasma glucose and triacylglycerol and hepatic glycogen
      were also measured. RESULTS: Dietary glutamine increased hepatic glycogen
      synthesis. Addition of dihydroxyacetone, with or without additional leucine,
      caused an additional increase in hepatic glycogen synthesis and increased the
      proportion of glycogen synthesized via pyruvate. Lipogenesis was not altered in
      the liver or adipose tissue. None of the dietary treatments had any effect on
      food intake, but the diets that contained dihydroxyacetone decreased the rate of
      weight gain. CONCLUSIONS: Increasing glycogen synthesis had no effect on food
      intake. Increasing the proportion of glycogen synthesized by the indirect pathway
      through pyruvate was associated with a decrease in weight gain.

PMID- 15723753
TI  - Nutritional assessment of raw and germinated pea (Pisum sativum L.) protein and
      carbohydrate by in vitro and in vivo techniques.
AB  - OBJECTIVE: We assessed the effect of germinating Pisum sativum L. variant Arvense
      cv. Esla for 3 and 6 d in darkness on the chemical composition and nutritive
      utilization of protein and carbohydrates. METHODS: Nutritional assessment of
      protein and carbohydrates was based on chemical analysis of raw and germinated
      pea flours and in vitro and in vivo rat balance methodologies. RESULTS:
      Germination caused a notable decrease in alpha-galactoside content and
      significant increases in sucrose, glucose, and fructose. The ratio of available
      starch to total starch increased as a consequence of processing. The content of
      vitamin B2 increased significantly, whereas no significant change was observed in
      vitamin B1 content in germinated peas. Protein digestibility assessed with an in
      vivo technique (apparent digestibility coefficient) or as the percentage of
      dialyzable nitrogen increased significantly as a result of germination in
      contrast to what was observed with the in vitro pH-drop methodology. Daily food
      intake, nitrogen absorption and balance, percentage of retained versus absorbed
      nitrogen, protein efficiency ratio, and the index of available carbohydrates were
      significantly improved by germination for 3 d and significantly decreased by
      germination for 6 d. CONCLUSIONS: Germination of pea seeds for 3 d significantly
      improves palatability of these seeds and the nutritive utilization of protein and
      carbohydrates.

PMID- 15723754
TI  - Changes in lipid metabolism and antioxidant defense status in spontaneously
      hypertensive rats and Wistar rats fed a diet enriched with fructose and saturated
      fatty acids.
AB  - OBJECTIVE: Larger doses of fructose and saturated fat have been associated with
      oxidative stress and development of hypertension. The effects of modest amounts
      of fructose and saturated fatty acids on oxidative stress are unknown. METHODS:
      To increase knowledge on this question, 10-wk-old spontaneously hypertensive rats
      and Wistar rats were fed for 8 wk with a control diet or an experimental diet
      enriched with fructose (18%) and saturated fatty acids (11%; FS diet). The total
      antioxidant status of organs and red blood cells was assayed by monitoring the
      rate of free radical-induced red blood cell hemolysis. Sensitivity of very low
      density lipoprotein and low-density lipoprotein (VLDL-LDL) to copper-induced
      lipid peroxidation was determined as the production of thiobarbituric acid
      reactive substances. Antioxidant enzymes and vitamins were also measured to
      establish the oxidative stress effect. RESULTS: The FS diet did not affect blood
      pressure in either strain, but it increased plasma insulin concentrations only in
      Wistar rats without affecting those of glucose of either strain. The FS diet
      significantly enhanced plasma and VLDL-LDL triacylglycerol concentrations without
      affecting concentrations of VLDL-LDL thiobarbituric acid-reactive substances. The
      decreased content of arachidonic acid and total polyunsaturated fatty acids in
      VLDL-LDL by the FS diet may have prevented lipid peroxidation in this fraction.
      Moreover, FS consumption by both strains was accompanied by a significant
      increase in total antioxidant capacity of adipose tissue, muscle, heart, and
      liver. This may have resulted from increased tissue ascorbic acid levels and
      glutathione peroxidase and glutathione reductase activities in tissues.
      CONCLUSIONS: These findings clearly indicate that the FS diet did not alter blood
      pressure of spontaneously hypertensive rats and Wistar rats. The FS diet resulted
      in hypertriglyceridemia but increased the total antioxidant status, which may
      prevent lipid peroxidation in these rats.

PMID- 15723755
TI  - Metabolic status in growing rats fed isocaloric diets with increased carbohydrate
      to-fat ratio.
AB  - OBJECTIVE: A low-fat diet is hypothesized to be associated with significant
      weight loss. However, most previous studies have been limited to low-fat, low
      calorie restrictive diets. This study evaluated the effect of isocaloric diets
      given "ad libitum" but different in relative amounts of fat and carbohydrate on
      body size, energy metabolism, body composition, insulin-like growth factor-1, and
      leptin serum levels in growing Wistar rats. METHODS: Weanling male rats were fed
      with one of three diets that contained a ratio of carbohydrate to fat of 1:1,
      2:1, or 3:1. Food intake, body weight, body length, oxygen consumption, and body
      composition were measured at ages 21 to 50 d. Serum levels of insulin-like growth
      factor-1 and leptin were also determined. RESULTS: Energy intake was similar
      across groups. The ratio of body weight to body length remained adequate
      throughout the experimental period. However, groups that received 3:1 and 2:1
      showed increased weight and progressive decreases in energy expenditure, body fat
      composition, and serum level of leptin, but the ratio of insulin-like growth
      factor-1 to body length was not affected. CONCLUSIONS: Dietary substitution of
      fat with carbohydrates contributes to weight gain by decreasing energy
      expenditure and possibly by decreasing leptin secretion.

PMID- 15723757
TI  - Hierarchy of nutritional knowledge that relates to the consumption of a
      functional food.
AB  - OBJECTIVE: We assessed how consumption of a functional food relates to different
      combinations of nutritional knowledge. METHODS: American and Canadian subjects
      were asked by mail survey about their level of knowledge about soy and were
      assigned to one of four groups based on whether they had 1) no knowledge of soy,
      2) attribute-related knowledge of soy, 3) consequence-related knowledge of
      consuming soy, or 4) both types of knowledge. Content analysis and analysis of
      variance were performed. RESULTS: The level of nutritional knowledge about soy
      did not necessarily influence how much people liked soy but was related to how
      much people consumed soy. In particular, consumers who were able to link
      attribute-related knowledge about soy to consequence-related knowledge about
      consuming soy were much more likely to consume soy than were those who only had
      one type of knowledge (average P < 0.007). CONCLUSIONS: Nutritional knowledge
      most likely correlates with consumption when people have attribute-related
      knowledge of the food and consequence-related knowledge of how it will benefit
      them. It is not the amount but the type of knowledge that matters. Educational
      strategies based only on attribute-related knowledge of functional foods and
      healthy products ("passing the nutrition quiz") may not effectively encourage the
      actual consumption of the food. Health care professionals and dietitians must
      link food attributes with personal health consequences when communicating to
      their patients.

PMID- 15723756
TI  - Effects of an immune-enhancing diet in endotoxemic rats.
AB  - OBJECTIVE: This work compared the nutritional efficiency of a recently available
      enteral formula enriched with arginine, omega-3 fatty acids, and antioxidants and
      supplied nitrogen as peptides (Crucial, Nestle Clinical Nutrition) with that of a
      standard polymeric formula (Sondalis HP, Nestle Clinical Nutrition) in
      endotoxemic rats. METHODS: Male Wistar rats (209 +/- 2 g) underwent catheter
      gastrostomy and received Sondalis HP until they recovered their preoperative
      weight. At that time (day 0), an endotoxemic shock was induced by an
      intraperitoneal injection of lipopolysaccharide (Escherichia coli, 8 mg/kg) and
      rats then received 290 kcal x kg(-1) x d(-1) and 3.29 g of nitrogen x kg(-1) x d(
      1) in the form of Crucial (IED group, n = 7) or Sondalis HP (S group, n = 6) for
      3 d. Another group underwent no treatment and was fed ad libitum (AL group). Rats
      were killed on day 3. Results are presented as mean +/- standard error of the
      mean (analysis of variance and Newman-Keuls test). RESULTS: The endotoxemic shock
      induced a weight loss in group S on days 1 and 2 and a weight gain in group IED (
      3.5 +/- 1.3 g in group S versus +6.0 +/- 2.2 g in group IED, P < 0.05). In the
      same way, atrophy of extensor digitorum longus muscle was observed in group S,
      whereas wasting was limited in group IED (102 +/- 4 mg in group IED versus 90 +/-
      3 mg in group S versus 119 +/- 3 mg in group AL, P < 0.05). Muscular atrophy was
      associated with muscular glutamine depletion and correlated with
      hyperphenylalaninemia (R = 0.60), with the latter being blunted in group IED (57
      +/- 1 microM/L in group AL versus 77 +/- 4 microM/L in group S versus 66 +/- 2
      microM/L in group IED, P < 0.05). No difference was observed between the
      experimental groups of endotoxemic rats with respect to nitrogen balance, urinary
      excretion of 3-methyl histidine, or total tissue protein content. CONCLUSION:
      Crucial counteracts injury-mediated weight loss, extensor digitorum longus muscle
      atrophy, and hyperphenylalaninemia in endotoxemic rats.

PMID- 15723758
TI  - Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food
      intake regulation.
AB  - Obesity is increasing in severity and prevalence in the United States and
      represents a major public health issue. No effective pharmacologic treatment
      leading to sustained weight loss currently exists. The growing interest in the
      regulation of food intake stems from the current drug treatments for obesity,
      almost all of which interfere with the monoamine system. Our knowledge of
      potential interactions between the orexigenic and anorexigenic pathways is
      limited and fragmented, making the development of targeted drug therapy for
      obesity difficult. The present review of the interaction of neuropeptides and
      monoamines emphasizes the complexity of the central mechanisms that regulate
      feeding behavior. Two main systems are implicated in food intake regulation:
      neuropeptide Y (NPY) and pro-opiomelanocortin. alpha-Melanocyte-stimulating
      hormone is a tridecapeptide cleaved from pro-opiomelanocortin that acts to
      inhibit food intake. The predominant NPY orexigenic receptors are NPY-Y1 and NPY
      Y5, and the two anorexigenic melanocortin receptors involved in hypothalamic food
      intake control are MC3-R and MC4-R. Both neuropeptides interact with monoamines
      in the hypothalamus to control physiologic states such as hunger, satiation, and
      satiety. Serotonin suppresses food intake and body weight, acting mainly through
      the serotonin 1B receptor. Dopamine regulates hunger and satiety by acting in
      specific hypothalamic areas, through the D1 and D2 receptors. Noradrenaline
      activation of alpha1- and beta2-adrenoceptors decreases food intake, and
      stimulation of the alpha2-adrenoceptor increases food intake. A better
      understanding of the detailed mechanisms underlying the pathogenesis of
      hyperphagia and hypophagia is needed to develop new therapeutic approaches to
      obesity.

PMID- 15723759
TI  - The art of using indirect calorimetry for nutritional assessment of sick infants
      and children.

PMID- 15723760
TI  - From immune-enhancing diets back to nutritional-enhancing diets.

PMID- 15723761
TI  - The epidemiology of chronic venous insufficiency and varicose veins.
AB  - Chronic venous disease is a common condition presenting to physicians in Western
      Europe and the United States. This article provides a comprehensive review of the
      published literature in the English language, from 1942 to the present, and
      focuses on the prevalence of chronic venous insufficiency and varicose veins, as
      well as the involved risk factors. Prevalence estimates vary widely by geographic
      location, with the highest reported rates in Western countries. Reports of
      prevalence of chronic venous insufficiency vary from < 1% to 40% in females and
      from < 1% to 17% in males. Prevalence estimates for varicose veins are higher,
      <1% to 73% in females and 2% to 56% in males. The reported ranges in prevalence
      estimations presumably reflect differences in the population distribution of risk
      factors, accuracy in application of diagnostic criteria, and the quality and
      availability of medical diagnostic and treatment resources. Established risk
      factors include older age, female gender, pregnancy, family history of venous
      disease, obesity, and occupations associated with orthostasis. Yet, there are
      several factors that are not well documented, such as diet, physical activity and
      exogenous hormone use, which may be important in the development of chronic
      venous disease and its clinical manifestations.

PMID- 15723762
TI  - Influence of atmospheric pressure, outdoor temperature, and weather phases on the
      onset of spontaneous pneumothorax.
AB  - PURPOSE: To analyze the influence of meteorological factors such as atmospheric
      pressure (AP), outdoor temperature (T) changes, and weather phases (WP) on the
      occurrence of spontaneous pneumothorax (SP). METHODS: Retrospective study,
      including 659 patients with primary SP and SP associated with chronic obstructive
      pulmonary disease (COPD), conservatively treated in a 5-year period. In the
      analyzed period, 548 days with SP were compared both with 3 days preceding the
      onset of SP and with days without pneumothorax. The comparison was made depending
      on weather phases and on different aspects of AP and T. RESULTS: Seasons of the
      year did not significantly influence the occurrence of SP. No significant
      difference was found between SP and non-SP days depending on different aspects of
      AP and T changes. Most patients were admitted in "clusters" with not more than 2,
      3, or 4 days between two successive admissions. The occurrence of SP was
      significantly correlated with weather phases 2ts (anticyclonic situation with
      warm and dry weather) and 5 hv (passing of the cold front). Biological sense and
      possible explanations of this correlation are discussed. CONCLUSIONS: Among all
      analyzed meteorological factors, significant correlation was found only between
      weather phases 2ts and 5hv and the occurrence of SP.

PMID- 15723763
TI  - The role of sexual assault on the risk of PTSD among Gulf War veterans.
AB  - PURPOSE: The 1991 Gulf War was the first major military deployment where female
      troops were integrated into almost every military unit, except for combat ground
      units. We evaluated the impact of reported sexual trauma during this deployment
      on the risk of post-traumatic stress disorder (PTSD) after the war. METHODS: A
      nested case-control analysis was conducted using the data collected in a
      population-based health survey of 30,000 Gulf War era veterans. A total of 1381
      Gulf War veterans with current PTSD were compared with 10,060 Gulf veteran
      controls without PTSD for self-reported in-theater experiences of sexual
      harassment/assault and combat exposure. RESULTS: The adjusted odds ratio (aOR)
      for PTSD associated with a report of sexual assault was 5.41 (95% confidence
      interval [CI], 3.19-9.17) in female veterans and 6.21 (95% CI, 2.26-17.04) in
      male veterans. The aOR for PTSD associated with "high" combat exposure was also
      statistically significant (aOR, 4.03 [95% CI, 1.97-8.23] for females; aOR, 4.45
      [95% CI, 3.54-5.60] for males). CONCLUSION: Notwithstanding a possibility of
      recall bias of combat and sexual trauma, for both men and women, sexual trauma as
      well as combat exposure appear to be strong risk factors for PTSD.

PMID- 15723764
TI  - Cholecystokinin A receptor gene promoter polymorphism and intelligence.
AB  - PURPOSE: To study the association between Cholecystokinin A receptor (CCKAR)
      genotypes and intelligence in community-living men and women. METHOD: Subjects
      were 2251 community-dwelling Japanese men and women aged 40 to 79 years. The
      CCKAR gene promoter polymorphisms A-81G and G-128T were determined. Intelligence
      was assessed by Japanese Wechsler Adult Intelligence Scales - Revised Short Forms
      (JWAIS-R SF). The difference in intelligence between wild type and mutation was
      tested. RESULTS: There were no subjects with AA/GT, AA/TT, or AG/TT genotypic
      combinations. Both A-81G and G-128T genotypes were related to intelligence
      quotient (IQ) estimated by JWAIS-R SF. The mean and SE of IQ levels of subjects
      with the wild-type allele and the mutation allele at nucleotide -128 were 103.4
      +/- 0.3 and 101.6 +/- 0.6, respectively. There was a significant difference in IQ
      for G-128T (p=0.008). The difference in IQ for A-81G was also significant
      (p=0.011). The IQ level was 103.6 +/- 0.4 in the subjects with the wild-type
      allele and 102.0 +/- 0.5 in the subjects with the mutation. Differences in IQ
      levels by haplotypes for combinations of A-81G/G-128T were examined. IQ
      significantly decreased with an increasing number of mutation alleles (p=0.018).
      CONCLUSION: There were statistically significant differences in IQ for CCKAR gene
      promoter polymorphisms A-81G and G-128T in community-living Japanese.

PMID- 15723765
TI  - Prevalence of the metabolic syndrome in relation to self-reported cancer history.
AB  - PURPOSE: To estimate the prevalence of metabolic syndrome in persons with a
      history of cancer from a population-based sample of adults, and compare that
      prevalence to persons without a history of cancer. METHODS: Data from the Third
      National Health and Nutrition Examination Survey were analyzed to compare
      prevalence and prevalence differences of the metabolic syndrome, as defined by
      Adult Treatment Panel III criteria, between 486 persons with a reported history
      of cancer and 12,526 persons with no reported history of cancer. RESULTS: The
      prevalence of metabolic syndrome was 258/1000 persons for those with a cancer
      history and 184/1000 persons among those without, resulting in a prevalence
      difference of 74/1000 persons (95% CI, 38-110). Prevalence differences varied
      substantially by age at interview. The prevalence difference was highest among
      those aged 40 to 49 years (112/1000 persons) and 50 to 59 years (73/1000
      persons), while those in younger (18-39 years) and older (: 60 years) age groups
      had a moderately higher prevalence among those without a cancer history.
      CONCLUSION: These results add to the emerging concern that metabolic syndrome and
      associated risks for cardiovascular disease and type 2 diabetes may be an adverse
      late effect of cancer and/or its treatment.

PMID- 15723766
TI  - Margarine consumption, asthma, and allergy in young adults: results of the German
      National Health Survey 1998.
AB  - PURPOSE: To examine whether frequent intake of margarine is associated with
      allergy prevalence in adults using data of a representative national health
      survey. METHODS: Data on 7124 subjects aged 18 to 79 years were obtained from the
      German National Health Survey 1998. Confounder-adjusted odds ratios (aOR) with
      95% confidence intervals (CI) were calculated by multiple logistic regression,
      using the frequency of intake of low-fat butter, regular and low-fat margarine as
      explanatory variable in relation to frequent intake of regular butter as
      reference group. RESULTS: Frequent intake of margarine of any kind was positively
      associated with current asthma during the past 12 months in young adults aged 18
      to 29 years (aOR, 2.33; 95% CI, 1.03-5.26). In subgroup analysis, the positive
      association was confined to frequent intake of low-fat margarine (4.51; 1.78
      11.43) or the combination of low-fat margarine and low-fat butter (4.79; 1.84
      12.44). Consumption of margarine of any kind was not related to hay fever, atopic
      dermatitis, and atopic sensitization to inhalant allergens. CONCLUSIONS: Frequent
      intake of margarine rich in n-6 PUFA is not consistently associated with allergic
      diseases in adults. Other constituents of low-fat margarine or certain dietary
      habits and lifestyle factors, characterized by use of low-fat margarine, may be
      related to current asthma.

PMID- 15723767
TI  - Does socio-demographic status influence the effect of pollens and molds on
      hospitalization for asthma? Results from a time-series study in 10 Canadian
      cities.
AB  - PURPOSE: Social status influences asthma morbidity but the mechanisms are not
      well understood. To determine if sociodemographics influence the susceptibility
      to ambient aeroallergens, we determined the association between daily
      hospitalizations for asthma and daily concentrations of ambient pollens and molds
      in 10 large Canadian cities. METHODS: Daily time-series analyses were performed
      and results were adjusted for day of the week, temperature, barometric pressure,
      relative humidity, ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide.
      Results were then stratified by age, gender, and neighborhood family education
      and income. RESULTS: There appeared to be age and gender interactions in the
      relation between aeroallergens and asthma. An increase in basidiomycetes
      equivalent to its mean value, about 300/m3, increased asthma admissions for
      younger males (under 13 years of age) by 9.3% (95% CI, 4.8%, 13.8%) vs. 4.2% (95%
      CI, - 0.1%, 8.5%) for older males. The reverse was true among females with
      increased effect in the older age group: 2.3% (95% CI, 1.2%, 5.8%) in those under
      13 years vs. 7.1% (95% CI, 4.1%, 10.1%) for older females. Associations were seen
      between aeroallergens and asthma hospitalization in the lowest but not the
      highest education group. CONCLUSIONS: Our results suggest that younger males and
      those within less educated families may be more vulnerable to aeroallergens as
      reflected by hospitalization for asthma.

PMID- 15723768
TI  - The use of sentinel injury deaths to evaluate the quality of multiple source
      reporting for occupational injuries.
AB  - PURPOSE: This study sought to develop an efficient method for evaluating the
      validity and completeness of routinely available sources of occupational injury
      fatality data. METHODS: Deaths due to falls from elevations, machinery, and
      electrocutions were selected as sentinel injuries likely to have occurred at
      work. Deaths from these injuries were identified from Maryland vital statistics
      over 7 years. The work-relatedness of these injuries and sensitivity of reporting
      were determined from death certificates, medical examiner reports, the National
      Traumatic Occupational Fatality System (NTOF), the Maryland Occupational Safety
      and Health Administration (MOSH), and Workers' Compensation (WC) data. RESULTS: A
      total of 527 deaths were identified for ages 16 and above, of which, 45% were
      work-related. Identification of work-related deaths varied by source: medical
      examiner (100%), death certificates (89%), NTOF (68%), MOSH (59%), and WC (44%).
      Reporting differed by age, cause of injury, year, occupation, and industry.
      CONCLUSIONS: Examination of work-relatedness for deaths from certain causes is an
      efficient means of evaluating the quality of occupational injury reporting source
      data. These sentinel injuries uncovered significant underreporting in sources
      used by national surveillance systems, resulted in improved NTOF reporting, and
      suggest the need to make more use of medical examiner data when available.

PMID- 15723769
TI  - Capacity building for epidemiologic research: a case study in the newly
      independent state of Azerbaijan.
AB  - PURPOSE: Because many emerging economies lack local capacity for scientific
      research, capacity building has become a priority for many international
      development organizations. This article describes and critiques an approach used
      for building local capacity for applied health research in Azerbaijan, one of the
      newly independent states (NIS) of the former USSR. METHODS: In 2000,
      environmental epidemiology training courses were conducted in Azerbaijan. Several
      local participants of these courses received hands-on training in the planning
      and conduct of a subsequent cancer study as a practical extension of the training
      exercises. RESULTS: The research demonstrated that international collaboration
      can not only result in the successful completion of health research in NIS such
      as Azerbaijan, but also impart research knowledge and experience to local
      experts. Several practical issues were encountered in the conduct of the training
      activities that limited their effectiveness. The most desired result (the
      proposal and conduct of new research by local experts trained through these
      exercises) has yet to be achieved to the levels expected. CONCLUSIONS:
      International collaborations such as the approach described here are useful for
      imparting expertise to researchers in less affluent countries. However,
      comprehensive capacity building programs providing ongoing professional
      development, support, and an enabling environment, rather than scientific
      training alone, are required to achieve long-term sustainability and measurable
      outcomes.

PMID- 15723770
TI  - Random digit dialing and directory-based samples in telephone surveys of HIV
      risk: a comparison from the Australian Study of Health and Relationships.
AB  - PURPOSE: To compare the estimates of HIV-related risk derived from a sample drawn
      through random digit dialing and that component of the sample drawn from
      households listed in a telephone directory. METHODS: The prevalence of key
      outcomes, and their 95% confidence intervals, was estimated for the total sample
      and for that component of the sample drawn from households listed in a telephone
      directory. RESULTS: On all outcome measures the sample derived from listed
      households was more conservative. With few exceptions, the estimates derived from
      the overall sample and from listed households were not significantly different.
      CONCLUSION: A continued reliance on random digit dialing seems unwarranted.

PMID- 15723772
TI  - Alarm bells ring over bird flu threat.

PMID- 15723771
TI  - Data collection for sexually transmitted disease diagnoses: a comparison of self
      report, medical record reviews, and state health department reports.
AB  - PURPOSE: To compare three methods of data collection on case ascertainment of
      past chlamydia or gonorrhea diagnoses. METHODS: Data collection for 361
      adolescent females between 1998 and 2000 included: 1) face-to-face interviews; 2)
      computerized and paper medical record reviews; and 3) chlamydia and gonorrhea
      reports to the state health department. Statistical methods include latent class
      and composite reference standard analyses. RESULTS: The estimated prevalence of
      past diagnoses did not differ significantly by data collection method for
      chlamydia (20.5%, 23.0%, and 19.7% by self-report, medical record reviews, and
      state health department reports, respectively) or gonorrhea (4.7%, 6.9%, and
      5.5%, respectively) during the 2-year study period. The estimated latent class
      and composite reference standard prevalences for chlamydia were 23.5% and 26.9%,
      respectively (p=.04 and p < .01 for differences from self-report alone,
      respectively). For gonorrhea, the estimated latent class and composite reference
      standard prevalences were 7.8% and 6.9%, respectively (p < .01 for both
      differences from self-report alone). Kappa scores for self-report compared with
      the latent class and composite reference standard prevalences ranged from .67 to
      .80, and the magnitude of under-reporting ranged from 21% to 47%. CONCLUSIONS:
      The similar case ascertainment from the three sources separately and high
      reliability of self-report, coupled with its feasibility and low cost, suggest
      that self-report is a viable data collection method for STD diagnoses. However,
      using multiple sources may be preferable when time and resources permit given
      that under-reporting by self-report is likely to occur (particularly for
      gonorrhea) and that greater case ascertainment can be achieved.

PMID- 15723773
TI  - Heavyweight attack on climate-change denial.

PMID- 15723774
TI  - Q & A. Carl R. Woese. [interview].

PMID- 15723775
TI  - Choanoflagellates.

PMID- 15723776
TI  - Sponges.

PMID- 15723777
TI  - Biological diversity.

PMID- 15723778
TI  - Functional conservation of an insect odorant receptor gene across 250 million
      years of evolution.
AB  - Pest insects have a profound negative impact on agriculture and human health.
      Significant global losses of crops, stored agricultural products, timber and
      livestock can be attributed to damage and destruction by insects . Blood-feeding
      insects such as mosquitoes, flies and ticks transmit many of humanity's most
      devastating infectious diseases. Insect-borne diseases account for more than one
      million annual fatalities, and insect-associated illnesses surpass 300 million
      annual reported cases . The medical and economic impact of these animals can be
      ascribed in part to the sensitivity and selectivity of their olfactory systems,
      essential for location of their preferred plant and animal hosts.

PMID- 15723779
TI  - Bonds smooth conflicts.

PMID- 15723780
TI  - Checkpoint signalling: Mad2 conformers and signal propagation.
AB  - The spindle checkpoint protein Mad2 has a tendency to form multimers and adopts
      at least two structural conformations. New work highlights the importance of the
      Mad2-Mad2 interaction, and suggests how spindle checkpoint signals are propagated
      away from kinetochores.

PMID- 15723781
TI  - Reproductive biology: direct delivery of costly sex peptides.
AB  - Research on seminal fluid proteins is providing fundamental insights into the
      interactive evolution of male and female reproductive strategies. Two new studies
      demonstrate, first, how an influential male sex peptide in Drosophila is
      delivered to the female bound directly onto sperm cells, and second, that its
      subsequent release has significant reproductive costs for females.

PMID- 15723782
TI  - Microtubule cytoskeleton: a new twist at the end.
AB  - A diverse group of proteins known as +TIPs specifically recognize the growing
      plus ends of microtubules in cells. Two recent papers on one such protein, CLIP
      170, provide new insights into the cellular functions of +TIPs as well as the
      mechanism by which they track microtubule ends.

PMID- 15723783
TI  - Sex chromosomes: evolution of the weird and wonderful.
AB  - New findings in the platypus and Drosophila pseudoobscura illustrate, yet again,
      that the sex chromosomes seem never to stop evolving. Degeneration processes lead
      to a continual loss of genes and gene activity on the Y chromosome, and complete
      loss of Y-linked genes is possible if autosomal genes take over control of male
      fertility - though addition of new material to the sex chromosomes may start the
      process anew.

PMID- 15723784
TI  - Heterochromatin: on the ADAR radar?
AB  - Vigilin proteins, the absence of which is known to cause abnormalities in
      heterochromatin, have been found to bind edited RNAs. Molecular complexes
      including vigilin comprise proteins involved with RNA editing and with DNA
      repair, making connections between these processes and RNA-based silencing
      mechanisms.

PMID- 15723785
TI  - Synapse formation: astrocytes spout off.
AB  - Trillions of synapses form as the brain develops. This intimate contact between
      two neurons has now been shown to be facilitated by thrombospondins - large
      extracellular matrix proteins secreted by astrocytes.

PMID- 15723786
TI  - Maize genetics: the treasure of the Sierra Madre.
AB  - Massive morphological changes occurred during the domestication of maize from
      wild teosinte. Some of the most important shifts are due to altered expression
      patterns of major regulatory genes.

PMID- 15723787
TI  - TOR signaling: an odyssey from cellular stress to the cell growth machinery.
AB  - The target of rapamycin (TOR) protein kinase is centrally involved in the
      coordination of cell growth and proliferation with the availability of growth
      factors and nutrients. Two recent reports have illuminated a mechanism whereby
      hypoxic stress dampens TOR signaling in metazoan cells.

PMID- 15723788
TI  - Smaug recruits the CCR4/POP2/NOT deadenylase complex to trigger maternal
      transcript localization in the early Drosophila embryo.
AB  - BACKGROUND: Asymmetric localization of mRNAs within cells promotes precise spatio
      temporal control of protein synthesis. Although cytoskeletal transport-based
      localization during Drosophila oogenesis is well characterized, little is known
      about the mechanisms that operate to localize maternal RNAs in the early embryo.
      One such mechanism-termed "degradation/protection"-acts on maternal Hsp83
      transcripts, removing them from the bulk cytoplasm while protecting them in the
      posterior pole plasm. RESULTS: Here, we identify the RNA binding protein, Smaug,
      previously known as a translational repressor of nanos, as a key regulator of
      degradation/protection-based transcript localization. In smaug mutants,
      degradation of Hsp83 transcripts is not triggered, and, thus, localization does
      not occur. Hsp83 transcripts are in an mRNP complex containing Smaug, but Smaug
      does not translationally repress Hsp83 mRNA. Rather, Smaug physically interacts
      with the CCR4/POP2/NOT deadenylase, recruiting it to Hsp83 mRNA to trigger
      transcript deadenylation and degradation. When Smaug is targeted to heterologous
      stable reporter transcripts in vivo, these are deadenylated and destabilized. A
      deletion that removes the gene encoding CCR4 exhibits dose-sensitive interactions
      with Smaug in both a loss-of-function and a gain-of-function context. Reduction
      of CCR4 protein levels compromises Hsp83 transcript destabilization. CONCLUSIONS:
      Smaug triggers destabilization and localization of specific maternal transcripts
      through recruitment of the CCR4/POP2/NOT deadenylase. In contrast, Smaug-mediated
      translational repression is accomplished via an indirect interaction between
      Smaug and eIF4E, a component of the basic translation machinery. Thus, Smaug is a
      multifunctional posttranscriptional regulator that employs distinct mechanisms to
      repress translation and to induce degradation of target transcripts.

PMID- 15723789
TI  - Cell divisions in the drosophila embryonic mesoderm are repressed via
      posttranscriptional regulation of string/cdc25 by HOW.
AB  - BACKGROUND: Cell-cycle progression is tightly regulated during embryonic
      development. In the Drosophila early embryo, the levels of String/Cdc25 define
      the precise timing and sites of cell divisions. However, cell-cycle progression
      is arrested in the mesoderm of gastrulating embryos despite a positive
      transcriptional string/cdc25 activation provided by the mesoderm-specific action
      of Twist. Whereas String/Cdc25 is negatively regulated by Tribbles in the
      mesoderm at these embryonic stages, the factor(s) controlling string/cdc25 mRNA
      levels has yet to be elucidated. RESULTS: Here, we show that the repressor
      isoform of the Drosophila RNA binding protein Held Out Wing [HOW(L)] is required
      to inhibit mesodermal cell division during gastrulation. Embryos mutant for how
      exhibited an excess of cell divisions, leading to delayed mesoderm invagination.
      The levels of the mitotic activator string/cdc25 mRNA in these embryos were
      significantly elevated. Protein-RNA precipitation experiments show that HOW(L)
      binds string/cdc25 mRNA. Overexpression of HOW(L) in Schneider cells reduces
      specifically the steady-state mRNA levels of a gfp reporter fused to string/cdc25
      untranslated region (3'UTR). CONCLUSIONS: Our results suggest that in wild-type
      embryos, string/cdc25 mRNA levels are downregulated by the repressor isoform
      HOW(L), which binds directly to string/cdc25 mRNA and regulates its degradation.
      Thus, we are proposing a novel posttranscriptional mechanism controlling cell
      cycle progression in the Drosophila embryo.

PMID- 15723790
TI  - The early extra petals1 mutant uncovers a role for microRNA miR164c in regulating
      petal number in Arabidopsis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small 20-25 nucleotide non-protein-coding RNAs
      that negatively regulate expression of genes in many organisms, ranging from
      plants to humans. The MIR164 family of miRNAs in Arabidopsis consists of three
      members that share sequence complementarity to transcripts of NAC family
      transcription factors, including CUP-SHAPED COTYLEDON1 (CUC1) and CUC2. CUC1 and
      CUC2 are redundantly required for the formation of boundaries between organ
      primordia. The analysis of transgenic plants that either overexpress miR164a or
      miR164b or express a miRNA-resistant version of CUC1 or CUC2 has shown that miRNA
      regulation of CUC1 and CUC2 is necessary for normal flower development. A loss-of
      function allele of MIR164b did not result in a mutant phenotype, possibly because
      of functional redundancy among the three members of the MIR164 family. RESULTS:
      In this study, we describe the characterization of the early extra petals1 (eep1)
      Arabidopsis mutant, whose predominant phenotype is the formation of extra petals
      in early-arising flowers. We demonstrate that eep1 is a loss-of-function allele
      of MIR164c, one of three known members of the MIR164 family. Our analyses of
      miR164c function and eep1 mir164b double mutants reveal that miR164c controls
      petal number in a nonredundant manner by regulating the transcript accumulation
      of the transcription factors CUC1 and CUC2. CONCLUSIONS: The data presented in
      this study indicate that closely related miRNA family members that are predicted
      to target the same set of genes can have different functions during development,
      possibly because of nonoverlapping expression patterns.

PMID- 15723791
TI  - Sex peptide causes mating costs in female Drosophila melanogaster.
AB  - Conflicts between females and males over reproductive decisions are common . In
      Drosophila, as in many other organisms, there is often a conflict over how often
      to mate. The mating frequency that maximizes male reproductive success is higher
      than that which maximizes female reproductive success . In addition, frequent
      mating reduces female lifespan and reproductive success , a cost that is mediated
      by male ejaculate accessory gland proteins (Acps) . We demonstrate here that a
      single Acp, the sex peptide (SP or Acp70A), which decreases female receptivity
      and stimulates egg production in the first matings of virgin females , is a major
      contributor to Acp-mediated mating costs in females. Females continuously exposed
      to SP-deficient males (which produce no detectable SP ) had significantly higher
      fitness and higher lifetime reproductive success than control females. Hence,
      rather than benefiting both sexes, receipt of SP decreases female fitness, making
      SP the first identified gene that is likely to play a central role in sexual
      conflict.

PMID- 15723792
TI  - The molecular basis of individual differences in phenylthiocarbamide and
      propylthiouracil bitterness perception.
AB  - Individual differences in perception are ubiquitous within the chemical senses:
      taste, smell, and chemical somesthesis . A hypothesis of this fact states that
      polymorphisms in human sensory receptor genes could alter perception by coding
      for functionally distinct receptor types . We have previously reported evidence
      that sequence variants in a presumptive bitter receptor gene (hTAS2R38) correlate
      with differences in bitterness recognition of phenylthiocarbamide (PTC) . Here,
      we map individual psychogenomic pathways for bitter taste by testing people with
      a variety of psychophysical tasks and linking their individual perceptions of the
      compounds PTC and propylthiouracil (PROP) to the in vitro responses of their
      TAS2R38 receptor variants. Functional expression studies demonstrate that five
      different haplotypes from the hTAS2R38 gene code for operatively distinct
      receptors. The responses of the three haplotypes we also tested in vivo correlate
      strongly with individuals' psychophysical bitter sensitivities to a family of
      compounds. These data provide a direct molecular link between heritable
      variability in bitter taste perception to functional variations of a single G
      protein coupled receptor that responds to compounds such as PTC and PROP that
      contain the N-C=S moiety. The molecular mechanisms of perceived bitterness
      variability have therapeutic implications, such as helping patients to consume
      beneficial bitter-tasting compounds-for example, pharmaceuticals and selected
      phytochemicals.

PMID- 15723793
TI  - The division of Drosophila germline stem cells and their precursors requires a
      specific cyclin.
AB  - A fundamental yet essentially unexplored question in stem cell biology is whether
      the stem cell cycle has specific features. Three B-cyclins in Drosophila, Cyclins
      (Cyc) A, B, and B3, associate with CDK1 and play partially redundant roles in
      embryogenic mitosis . Here, we show that the division of Drosophila GSCs and
      their precursors, the primordial germ cells (PGCs), specifically requires CycB.
      CycB is ubiquitously expressed in both germline and somatic lineages. However,
      CycB mutation does not have obvious effect on somatic development but causes PGCs
      to severely under proliferate. Moreover, both female and male CycB mutant GSCs
      fail to be maintained properly. Removing Cyclin B specifically from female GSCs
      causes the same defect, confirming the direct and cell-autonomous function of
      Cyclin B for GSC division. In contrast, two other G2 cyclins, CycA and CycB3, are
      also expressed in PGCs and GSCs, but overexpressing CycA cannot rescue the CycB
      mutant defects. These results indicate that the requirement of CycB for PGC and
      GSC divisions unlikely reflects the insufficient level of G2 cyclins in the CycB
      mutant but is in favor of a distinct function of CycB in these cells. Our results
      indicate that stem cells may use specific cell cycle regulators for their
      division.

PMID- 15723794
TI  - The Drosophila Grp/Chk1 DNA damage checkpoint controls entry into anaphase.
AB  - It is well established that DNA damage induces checkpoint-mediated interphase
      arrest in higher eukaryotes, but recent studies demonstrate that DNA damage
      delays entry into anaphase as well. Damaged DNA in syncytial and gastrulating
      Drosophila embryos delays the metaphase/anaphase transition . In human cultured
      cells, DNA damage also induces a delay in mitosis . However, the mechanism by
      which DNA damage delays the anaphase onset is controversial. Some studies
      implicate a DNA damage checkpoint , whereas other studies invoke a spindle
      checkpoint . To resolve this issue, we compared the effects of random DNA breaks
      induced by X-irradiation to site-specific I-CreI endonuclease-induced chromosome
      breaks on cell-cycle progression in wild-type and checkpoint-defective Drosophila
      neuroblasts. We found that both the BubR1 spindle checkpoint pathway and the
      Grp/Chk1 DNA damage checkpoint pathway are involved in delaying the
      metaphase/anaphase transition after extensive X-irradiation-induced DNA damage,
      whereas Grp/Chk1, but not BubR1, is required to delay anaphase onset in the
      presence of I-CreI-induced double-strand breaks. On the basis of these results,
      we propose that DNA damage in nonkinetochore regions produces a Grp/Chk1 DNA
      damage-checkpoint-mediated delay in the metaphase/anaphase transition.

PMID- 15723795
TI  - Expression profiling of GABAergic motor neurons in Caenorhabditis elegans.
AB  - Neurons constitute the most diverse cell types and acquire their identity by the
      activity of particular genetic programs . The GABAergic nervous system in C.
      elegans consists of 26 neurons that fall into six classes . Animals that are
      defective in GABAergic neuron function and development display "shrinker"
      movement , abnormal foraging and defecation . Among the known shrinker genes, unc
      25 and unc-47 encode the GABA biosynthetic enzyme glutamic acid decarboxylase and
      vesicular transporter, respectively . unc-30 encodes a homeodomain protein of the
      Pitx family and regulates the differentiation of the D-type GABAergic neurons .
      unc-46 probably functions in presynaptic GABA release , but its identity has not
      been reported. By cell-based microarray analysis, we identified over 250 genes
      with enriched expression in GABAergic neurons. The highly enriched gene set
      included all known genes. In vivo expression study with computational predictions
      further identified six new genes that are potential transcriptional targets of
      UNC-30. Behavioral studies of a deletion mutant implicate a function of a
      nicotinic receptor subunit in D-type neurons. Our analysis demonstrates the
      utility of neuron-specific genomics in identifying cell-specific genes and
      regulatory networks.

PMID- 15723796
TI  - Identification of transcriptional regulatory elements in chemosensory receptor
      genes by probabilistic segmentation.
AB  - Genome sequencing has allowed many gene regulatory elements to be identified
      through cross-species comparisons . However, the expression of genes in multigene
      families can diverge rapidly between related species . An alternative approach to
      characterizing multigene families utilizes the fact that genes within the group
      are likely to share aspects of their regulation. Here, we use a statistical
      approach, probabilistic segmentation , to identify sequences that are
      overrepresented in the regions upstream of C. elegans chemosensory receptor
      genes. Although each of these elements is present in only a subset of the genes,
      their distribution across and within the promoters of chemosensory receptor genes
      makes it possible to detect them. Many of the motifs show positional preference
      with respect to the translational start site and correspond to the binding sites
      of known families of transcription factors. We verified one motif, the E-box
      sequence WWYCACSTGYY, by showing that it directs expression of reporter genes to
      the ADL chemosensory neurons. Thus, probabilistic segmentation can be used to
      identify functional regulatory elements with no previous knowledge of gene
      expression or regulation. This approach may be of particular value for rapidly
      evolving genes in the immune system and the nervous system.

PMID- 15723797
TI  - Human Bub1 defines the persistent cohesion site along the mitotic chromosome by
      affecting Shugoshin localization.
AB  - Shugoshin (Sgo) proteins constitute a conserved protein family defined as
      centromeric protectors of Rec8-containing cohesin complexes in meiosis . In
      vertebrate mitosis, Scc1/Rad21-containing cohesin complexes are also protected at
      centromeres because arm cohesin, but not centromeric cohesin, is largely
      dissociated in pro- and prometaphase . The dissociation process is dependent on
      the activity of polo-like kinase (Plk1) and partly dependent on Aurora B .
      Recently, it has been demonstrated that vertebrate shugoshin is required for
      preserving centromeric cohesion during mitosis ; however, it was not addressed
      whether human shugoshin protects cohesin itself. Here, we show that the
      persistence of human Scc1 at centromeres in mitosis is indeed dependent on human
      Sgo1. In fission yeast, Sgo localization depends on Bub1, a conserved spindle
      checkpoint protein, which is enigmatically also required for chromosome
      congression during prometaphase in vertebrate cells. We demonstrate that human
      Sgo1 fails to localize at centromeres in Bub1-repressed cells, and centromeric
      cohesion is significantly loosened. Remarkably, in these cells, Sgo1 relocates to
      chromosomes all along their length and provokes ectopic protection from
      dissociation of Scc1 on chromosome arms. These results reveal a hitherto
      concealed role for human Bub1 in defining the persistent cohesion site of mitotic
      chromosomes.

PMID- 15723798
TI  - Endocytic delivery to lysosomes mediated by concurrent fusion and kissing events
      in living cells.
AB  - In mammalian cells, macromolecules internalized by endocytosis are transported
      via endosomes for digestion by lysosomal acid hydrolases . The mechanism by which
      endosomes and lysosomes exchange content remains equivocal . However, lysosomes
      are reusable organelles because they remain accessible to endocytic enzyme
      replacement therapies and undergo content mixing with late endosomes . The
      maturation model, which proposes that endosomes mature into lysosomes , cannot
      explain these observations. Three mechanisms for content mixing have been
      proposed. The first is vesicular transport, best supported by a yeast cell-free
      assay . The second suggests that endosomes and lysosomes engage in repeated
      transient fusions termed "kiss-and-run" . The third is that endosomes and
      lysosomes fuse completely, yielding hybrid compartments from which lysosomes
      reform , termed "fusion-fission" . We utilized time-lapse confocal microscopy to
      test these hypotheses in living cells. Lysosomes were loaded with rhodamine
      dextran by pulse-chase, and subsequently late endosomes were loaded with Oregon
      green 488 dextran. Direct fusions were observed between endosomes and lysosomes,
      and one such event was captured by correlative electron microscopy. Fluorescence
      intensity analyses of endosomes that encountered lysosomes revealed a gradual
      accumulation of lysosomal content. Our data are compatible with a requirement for
      direct contact between organelles before content is exchanged.

PMID- 15723799
TI  - Ras-independent activation of ERK signaling via the torso receptor tyrosine
      kinase is mediated by Rap1.
AB  - In Drosophila embryos, the Torso receptor tyrosine kinase (RTK) activates the
      small G protein Ras (D-Ras1) and the protein kinase Raf (D-Raf) to activate ERK
      to direct differentiation of terminal structures . However, genetic studies have
      demonstrated that Torso, and by extension other RTKs, can activate Raf and ERK
      independently of Ras . In mammalian cells, the small G protein Rap1 has been
      proposed to couple RTKs to ERKs. However, the ability of Rap1 to activate ERKs
      remains controversial, in part because direct genetic evidence supporting this
      hypothesis is lacking. Here, we present biochemical and genetic evidence that D
      Rap1, the Drosophila homolog of Rap1, can activate D-Raf and ERK. We show that D
      Rap1 binds D-Raf and activates ERKs in a GTP- and D-Raf-dependent manner.
      Targeted disruption of D-Rap1 expression decreased both Torso-dependent ERK
      activation and the ERK-dependent expression of the zygotic genes tailless and
      huckebein to levels similar to those achieved in D-Ras1 null embryos.
      Furthermore, combined deficiencies of D-Ras1 and D-Rap1 completely abolished
      expression of these genes, mimicking the phenotype observed in embryos lacking D
      Raf. These studies provide the first direct genetic evidence of Rap1-mediated
      activation of the MAP kinase cascade in eukaryotic organisms.

PMID- 15723800
TI  - A Steric-inhibition model for regulation of nucleotide exchange via the Dock180
      family of GEFs.
AB  - CDM (CED-5, Dock180, Myoblast city) family members have been recently identified
      as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for
      Rho-family GTPases . They regulate multiple processes, including embryonic
      development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1
      infection, in diverse model systems . However, the mechanism(s) of regulation of
      CDM proteins has not been well understood. Here, our studies on the prototype
      member Dock180 reveal a steric-inhibition model for regulating the Dock180 family
      of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the
      distant catalytic Docker domain and negatively regulates the function of Dock180.
      Further studies revealed that the SH3:Docker interaction sterically blocks Rac
      access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of
      Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the
      Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex.
      Additional genetic rescue studies in C. elegans suggested that the regulation of
      the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining
      region is evolutionarily conserved. This steric-inhibition model may be a general
      mechanism for regulating multiple SH3-domain-containing Dock180 family members
      and may have implications for a variety of biological processes.

PMID- 15723801
TI  - A member of the polymerase beta nucleotidyltransferase superfamily is required
      for RNA interference in C. elegans.
AB  - RNA interference (RNAi) is an ancient, highly conserved mechanism in which small
      RNA molecules (siRNAs) guide the sequence-specific silencing of gene expression .
      Several silencing machinery protein components have been identified, including
      helicases, RNase-related proteins, double- and single-stranded RNA binding
      proteins, and RNA-dependent RNA polymerase-related proteins . Work on these
      factors has led to the revelation that RNAi mechanisms intersect with cellular
      pathways required for development and fertility . Despite rapid progress in
      understanding key steps in the RNAi pathway, it is clear that many factors
      required for both RNAi and related developmental mechanisms have not yet been
      identified. Here, we report the characterization of the C. elegans gene rde-3.
      Genetic analysis of presumptive null alleles indicates that rde-3 is required for
      siRNA accumulation and for efficient RNAi in all tissues, and it is essential for
      fertility and viability at high temperatures. RDE-3 contains conserved domains
      found in the polymerase beta nucleotidyltransferase superfamily, which includes
      conventional poly(A) polymerases, 2'-5' oligoadenylate synthetase (OAS), and
      yeast Trf4p . These findings implicate a new enzymatic modality in RNAi and
      suggest possible models for the role of RDE-3 in the RNAi mechanism.

PMID- 15723802
TI  - Vigilins bind to promiscuously A-to-I-edited RNAs and are involved in the
      formation of heterochromatin.
AB  - The fate of double-stranded RNA (dsRNA) in the cell depends on both its length
      and location . The expression of dsRNA in the nucleus leads to several distinct
      consequences. First, the promiscuous deamination of adenosines to inosines by
      dsRNA-specific adenosine deaminase (ADAR) can lead to the nuclear retention of
      edited transcripts . Second, dsRNAs might induce heterochromatic gene silencing
      through an RNAi-related mechanism . Is RNA editing also connected to
      heterochromatin? We report that members of the conserved Vigilin class of
      proteins have a high affinity for inosine-containing RNAs. In agreement with
      other work , we find that these proteins localize to heterochromatin and that
      mutation or depletion of the Drosophila Vigilin, DDP1, leads to altered nuclear
      morphology and defects in heterochromatin and chromosome segregation.
      Furthermore, nuclear Vigilin is found in complexes containing not only the
      editing enzyme ADAR1 but also RNA helicase A and Ku86/70. In the presence of RNA,
      the Vigilin complex recruits the DNA-PKcs enzyme, which appears to phosphorylate
      a discrete set of targets, some or all of which are known to participate in
      chromatin silencing. These results are consistent with a mechanistic link between
      components of the DNA-repair machinery and RNA-mediated gene silencing.

PMID- 15723803
TI  - Immunity: it's in our bones.
AB  - Accumulating data suggest that the bone marrow is a reservoir for memory CD8+ T
      cells. In this issue of Immunity, show that bone marrow CD8+ T cells are
      predominantly CCR7+/CD62L+ "central memory" cells and describe specific signals
      that mediate their constitutive recruitment from the blood.

PMID- 15723804
TI  - Prions, cytokines, and chemokines: a meeting in lymphoid organs.

PMID- 15723805
TI  - Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of
      a highly conserved fusion-associated motif in gp41.
AB  - Broadly neutralizing monoclonal antibodies to HIV-1 are rare but invaluable for
      vaccine design. 4E10 is the broadest neutralizing antibody known and recognizes a
      contiguous and highly conserved epitope in the membrane-proximal region of gp41.
      The crystal structure of Fab 4E10 was determined at 2.2 A resolution in complex
      with a 13-residue peptide containing the gp41 core epitope (NWFDIT). The bound
      peptide adopts a helical conformation in which the key contact residues, TrpP672,
      PheP673, IleP675, and ThrP676, map to one face of the helix. The peptide binds in
      a hydrophobic pocket that may emulate its potential interaction with the host
      cell membrane. The long CDR H3 of the antibody extends beyond the bound peptide
      in an orientation that suggests that its apex could contact the viral membrane
      when 4E10 is bound to its membrane-proximal epitope. These structural insights
      should assist in the design of immunogens to elicit 4E10-like neutralizing
      responses.

PMID- 15723806
TI  - Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor
      site by crosspresenting APCs.
AB  - Expression of tissue-specific homing molecules directs antigen-experienced T
      cells to particular peripheral tissues. In studies using soluble antigens that
      focused on skin and gut, antigen-presenting cells (APCs) within regional lymphoid
      tissues were proposed to be responsible for imprinting homing phenotypes. Whether
      this occurs in other sites and after physiologic antigen processing and
      presentation is unknown. We define in vivo imprinting of distinct homing
      phenotypes on monospecific T cells responding to antigens expressed by tumors in
      intracerebral, subcutaneous, and intraperitoneal sites with efficient brain
      tropism of CD8 T cells crossprimed in the cervical lymph nodes (LNs). Multiple
      imprinting programs could occur simultaneously in the same LN when tumors were
      present in more than one site. Thus, the identity of the LN is not paramount in
      determining the homing phenotype; this critical functional parameter is dictated
      upstream at the site of antigen capture by crosspresenting APCs.

PMID- 15723807
TI  - Immunological synapses are versatile structures enabling selective T cell
      polarization.
AB  - Helper T cells discriminate among different antigen-presenting cells to provide
      their help in a selective fashion. The molecular mechanisms leading to this
      exquisite selectivity are still elusive. Here, we demonstrate that immunological
      synapses are dynamic and adaptable structures allowing T cells to communicate
      with multiple cells. We show that T cells can form simultaneous immunological
      synapses with cells presenting different levels of antigenic ligands but
      eventually polarize toward the strongest stimulus. Remarkably, living T cells
      form discrete foci of signal transduction of different intensities during the
      interaction with different antigen-presenting cells and rapidly relocate TCR and
      Golgi apparatus toward the cell providing the strongest stimulus. Our results
      illustrate that, although T cell activation requires sustained signaling, T cells
      are capable of rapid synapse remodeling and swift polarization responses. The
      combination of sustained signaling with preferential and rapid polarization
      provides a mechanism for the high sensitivity and selectivity of T cell
      responses.

PMID- 15723808
TI  - VDUP1 is required for the development of natural killer cells.
AB  - Vitamin D3 upregulated protein 1 (VDUP1) is a stress-response gene that is
      upregulated by 1,25(OH)2D3 in tumor cells. The in vivo roles of VDUP1 were
      investigated by producing mice lacking VDUP1 (VDUP1-/- mice). VDUP1-/- mice
      showed minimal changes in the development of T and B cells, but there was a
      profound reduction in the numbers of natural killer (NK) cells. As well, these
      mice showed decreased NK activity. In the VDUP1-/- mice, the expression of CD122
      was reduced, demonstrating that VDUP1 is required for CD122 expression and NK
      maturation. In addition, severe lymphoid hyperplasia in the small intestine was
      observed in VDUP1-/- mice. Taken together, these results suggest that VDUP1 is a
      critical factor for the development and function of NK cells in vivo.

PMID- 15723809
TI  - Molecular mechanism of lipopeptide presentation by CD1a.
AB  - CD1a is expressed on Langerhans cells (LCs) and dendritic cells (DCs), where it
      mediates T cell recognition of glycolipid and lipopeptide antigens that contain
      either one or two alkyl chains. We demonstrate here that CD1a-restricted T cells
      can discriminate the peptide component of didehydroxymycobactin lipopeptides.
      Structure analysis of CD1a cocrystallized with a synthetic mycobactin lipopeptide
      at 2.8 A resolution further reveals that the single alkyl chain is inserted deep
      within the A' pocket of the groove, whereas its two peptidic branches protrude
      along the F' pocket to the outer, alpha-helical surface of CD1a for recognition
      by the TCR. Remarkably, the cyclized lysine branch of the peptide moiety lies in
      the shallow F' pocket in a conformation that closely mimics that of the alkyl
      chain in the CD1a-sulfatide structure. Thus, this structural study illustrates
      how a single chain lipid can be presented by CD1 and that the peptide moiety of
      the lipopeptide is recognized by the TCR.

PMID- 15723810
TI  - Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome
      induced immune escape.
AB  - Major Histocompatibility Complex (MHC) class II molecules, including Human
      Leukocyte Antigen (HLA)-DR, present peptide fragments from proteins degraded in
      the endocytic pathway. HLA-DR is targeted to late-endocytic structures named MHC
      class II-containing Compartments (MIIC), where it interacts with HLA-DM. This
      chaperone stabilizes HLA-DR during peptide exchange and is critical for
      successful peptide loading. To follow this process in living cells, we have
      generated cells containing HLA-DR3/Cyan Fluorescent Protein (CFP), HLA-DM/Yellow
      Fluorescent Protein (YFP), and invariant chain. HLA-DR/DM interactions were
      observed by Fluorescence Resonance Energy Transfer (FRET). These interactions
      were pH insensitive, yet occurred only in internal structures and not at the
      limiting membrane of MIIC. In a cellular model of infection, phagosomes formed a
      limiting membrane surrounding internalized Salmonella. HLA-DR and HLA-DM did not
      interact in Salmonella-induced vacuoles, and HLA-DR was not loaded with antigens.
      The absence of HLA-DR/DM interactions at the limiting membrane prevents local
      loading of MHC class II molecules in phagosomes. This may allow these bacteria to
      successfully evade the immune system.

PMID- 15723811
TI  - The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic
      cell chemokine signaling via PIR-B.
AB  - In classical descriptions of leukocyte chemokine signaling, Src family kinases
      are thought to function in a positive fashion by coupling receptor associated
      Galpha subunits to downstream mitogen activated protein (MAP) kinase activation.
      However, neutrophils derived from hck-/-fgr-/- mice and dendritic cells (DCs)
      from fgr-/- animals manifested significantly higher intracellular signaling (Ca2+
      flux, MAP kinase activation, actin polymerization) and functional responses
      (chemotaxis in vitro and migration in vivo) to a number of different chemokines.
      These kinases may mediate their effect through the inhibitory receptor PIR-B
      since neutrophils and DCs from pir-b-/- mice were also hyperresponsive to
      chemokine stimulation. In wild-type (wt) cells dephosphorylation of PIR-B was
      associated with maximal chemokine signaling, whereas in hck-/-fgr-/- cells PIR-B
      was unphosphorylated. These data support a model in which the Src family kinases
      Hck and Fgr function as negative regulators of myeloid cell chemokine signaling
      by maintaining the tonic phosphorylation of PIR-B.

PMID- 15723812
TI  - Viruses evade the immune system through type I interferon-mediated STAT2
      dependent, but STAT1-independent, signaling.
AB  - Understanding, treating, and preventing diseases caused by immunosuppression
      and/or persistent infections remain both a major challenge in biomedical research
      and an important health goal. For a virus or any infectious agent to persist, it
      must utilize strategies to suppress or evade the host's immune response. Here, we
      report that two dissimilar viruses employ a common maneuver to cause a profound
      immunosuppression. Measles virus (MV) and lymphocytic choriomeningitis virus
      (LCMV) interfere with dendritic cell (DC) development and expansion in vivo and
      in vitro. The underlying mechanism for this is through the generation of type I
      interferon (IFN) that acts via a signal transducer and activator of a
      transcription (STAT)2-dependent, but STAT1-independent, pathway. Thus, viruses
      subvert the known antiviral effect of type I IFN through STAT2-specific signaling
      to benefit their survival. These observations have implications for understanding
      and developing therapies to treat diseases caused by immunosuppression and/or
      persistent infections.

PMID- 15723814
TI  - A proteomic analysis of human hemodialysis fluid.
AB  - The vascular compartment is an easily accessible compartment that provides an
      opportunity to measure analytes for diagnostic, prognostic, or therapeutic
      indications. Both serum and plasma have been analyzed extensively by proteomic
      approaches in an effort to catalog all proteins and polypeptides. Limitations of
      such approaches in obtaining a comprehensive catalog of proteins include the fact
      that a handful of proteins constitute over 90% of plasma protein content and that
      the renal glomeruli filter out proteins and polypeptides that are smaller than 66
      kDa from blood. We chose to study hemodialysis fluid because it contains a higher
      concentration of small proteins and polypeptides and is also simultaneously
      depleted of the most abundant proteins present in blood. Using gel
      electrophoresis in combination with LC-MS/MS, we identified 292 proteins of which
      greater than 70% had not been previously identified from serum or plasma. More
      than half of the proteins identified from the hemodialysis fluid were smaller
      than 40 kDa. We also found 50 N-terminally acetylated peptides that allowed us to
      unambiguously map the N termini of mature forms of the corresponding proteins.
      Several identified proteins, including cytokines, were only present as predicted
      transcripts in data bases and thus represent novel proteins. The proteins
      identified in this study could serve as biomarkers in serum using more sensitive
      methods such as ELISA-specific antibodies.

PMID- 15723813
TI  - Bone marrow is a major reservoir and site of recruitment for central memory CD8+
      T cells.
AB  - Normal bone marrow (BM) contains T cells whose function and origin are poorly
      understood. We observed that CD8+ T cells in BM consist chiefly of CCR7+ L
      selectin+ central memory cells (TCMs). Adoptively transferred TCMs accumulated
      more efficiently in the BM than naive and effector T cells. Intravital microscopy
      (IVM) showed that TCMs roll efficiently in BM microvessels via L-, P-, and E
      selectin, whereas firm arrest required the VCAM-1/alpha4beta1 pathway.
      alpha4beta1 integrin activation did not depend on pertussis toxin (PTX)-sensitive
      Galphai proteins but was reduced by anti-CXCL12. In contrast, TCM diapedesis did
      not require CXCL12 but was blocked by PTX. After extravasation, TCMs displayed
      agile movement within BM cavities, remained viable, and mounted potent antigen
      specific recall responses for at least two months. Thus, the BM functions as a
      major reservoir for TCMs by providing specific recruitment signals that act in
      sequence to mediate the constitutive recruitment of TCMs from the blood.

PMID- 15723815
TI  - Clopidogrel administration prior to coronary artery bypass grafting surgery: the
      cardiologist's panacea or the surgeon's headache?
AB  - AIMS: Thrombotic complications after percutaneous coronary intervention
      procedures have decreased in past years mainly due to the use of clopidogrel
      antiplatelet therapy. However, the risk of bleeding due to enhanced and
      irreversible platelet inhibition in patients who will require surgical coronary
      revascularization instead has not been adequately addressed in the literature.
      The purpose of this study was to evaluate the effect of pre-operative clopidrogel
      exposure in haemorrhage-related re-exploration rates, peri-operative transfusion
      requirements, morbidity, and mortality in patients undergoing coronary artery
      bypass grafting (CABG) surgery. METHODS AND RESULTS: A study population of 2359
      patients undergoing isolated CABG between January 2000 and June 2002 was
      reviewed. Of these, 415 (17.6%) received clopidogrel prior to CABG surgery, and
      1944 (82.4%) did not. A risk-adjusted logistic regression analysis was used to
      assess the association between clopidogrel pre-medication (vs. no) and
      haemostatic re-operation, intraoperative and post-operative blood transfusion
      rates, and multiple transfusions received. Haemorrhage-related pre-operative risk
      factors identified from the literature and those found significant in a
      univariate model were used. Furthermore, a sub-cohort, matched-pair by propensity
      scores analysis, was also conducted. The clopidogrel group had a higher
      likelihood of haemostatic re-operation [OR = 4.9, (95% CI, 2.63-8.97), P < 0.01],
      an increase in total packed red blood cell transfusions [OR = 2.2, (95% CI, 1.70
      2.84), P < 0.01], multiple unit blood transfusions [OR = 1.9, (95% CI, 1.33
      2.75), P < 0.01] and platelet transfusions [OR = 2.6, (95% CI, 1.95-3.56), P <
      0.01]. Surgical outcomes and operative mortality [OR = 1.5, (95% CI, 0.36-6.51),
      P = 0.56] were not significantly different. CONCLUSION: Pre-operative clopidogrel
      exposure increases the risk of haemostatic re-operation and the requirements for
      blood and blood product transfusion during, and after, CABG surgery.

PMID- 15723816
TI  - Undertreatment of acute pain in the emergency department: a challenge.
AB  - OBJECTIVE: Evaluation and improvement of pain management in our emergency
      department (ED). DESIGN: This was a "before-after" study. For each subject, the
      nurse, the physician, and the patient were asked to rate the initial intensity of
      the pain on a Visual Analogue Score (VAS). The timing and the type of analgesics
      administered were then recorded and follow-up VAS was performed. SETTING: A
      teaching, community-based, 400-bed hospital. STUDY PARTICIPANTS: 140 patients
      admitted for acute pain related to orthopedic injuries. MAIN OUTCOME MEASURES:
      The gap between the VAS expressed by the patient and estimated by the staff, the
      proportion of patients receiving analgesics, and the length of time delays
      between admission and analgesic administration. INTERVENTION: The intervention
      included education of medical and nursing staffs, insertion of a VAS template in
      the patient's chart, initiation of routine VAS assessment and re-assessment, and
      implementation of a protocol for pain management with standing orders for nurses.
      RESULTS: The VAS gap between the patient and the nurse decreased significantly
      from 1.91 2.04 to 1.03 1.97 after the intervention (P = 0.01). The percentage of
      patients receiving analgesics rose from 70 to 82% following the intervention.
      Time from admission to analgesia decreased from 80 +/- 68 min (mean +/- SD)
      before the intervention, to 58 +/- 37 min after the intervention (P = 0.05).
      CONCLUSION: Inadequate pain management in the ED appears related to poor staff
      assessment of pain and may be improved by routine VAS recording and by a nurse
      based pain protocol.

PMID- 15723817
TI  - The JCAHO patient safety event taxonomy: a standardized terminology and
      classification schema for near misses and adverse events.
AB  - BACKGROUND: The current US national discussions on patient safety are not based
      on a common language. This hinders systematic application of data obtained from
      incident reports, and learning from near misses and adverse events. OBJECTIVE: To
      develop a common terminology and classification schema (taxonomy) for collecting
      and organizing patient safety data. METHODS: The project comprised a systematic
      literature review; evaluation of existing patient safety terminologies and
      classifications, and identification of those that should be included in the core
      set of a standardized taxonomy; assessment of the taxonomy's face and content
      validity; the gathering of input from patient safety stakeholders in multiple
      disciplines; and a preliminary study of the taxonomy's comparative reliability.
      RESULTS: Elements (terms) and structures (data fields) from existing
      classification schemes and reporting systems could be grouped into five
      complementary root nodes or primary classifications: impact, type, domain, cause,
      and prevention and mitigation. The root nodes were then divided into 21
      subclassifications which in turn are subdivided into more than 200 coded
      categories and an indefinite number of uncoded text fields to capture narrative
      information. An earlier version of the taxonomy (n = 111 coded categories)
      demonstrated acceptable comparability with the categorized data requirements of
      the ICU safety reporting system. CONCLUSIONS: The results suggest that the Joint
      Commission on Accreditation of Healthcare Organizations (JCAHO) Patient Safety
      Event Taxonomy could facilitate a common approach for patient safety information
      systems. Having access to standardized data would make it easier to file patient
      safety event reports and to conduct root cause analyses in a consistent fashion.

PMID- 15723818
TI  - Adherence to management guidelines in acute respiratory infections and diarrhoea
      in children under 5 years old in primary health care in Botswana.
AB  - OBJECTIVE: To evaluate health care providers' adherence to management guidelines
      for acute respiratory infection and diarrhoea in children under 5 years old in
      Botswana primary health care. DESIGN: Cross-sectional prospective field survey.
      Data collection was carried out through observation of consecutive consultations
      at 30 randomly assigned clinics and health posts in three purposely chosen
      districts. STUDY PARTICIPANTS: This study comprises 185 cases of acute
      respiratory infection and 85 cases of diarrhoea. MAIN MEASURE: Criteria for
      acceptable standards of history taking and physical examination for acute
      respiratory infection and diarrhoea were defined as well as criteria for
      categorizing the appropriateness of antibiotic prescription. The percentage of
      oral dehydration salts provided in cases of diarrhoea was calculated. RESULTS:
      Acute respiratory infection and diarrhoea accounted for 270 (including 15 missing
      cases) of all main diagnoses (n = 539). In 262 cases (97%) health care providers
      were nurses or enrolled nurses; in 3% family welfare educators. Acceptable
      history taking, physical examination, and both combined in acute respiratory
      infection was found in 113 (63%), 32 (18%), and 28 (16%), and in diarrhoea in 45
      (58%), 26 (34%) and 20 (26%) cases, respectively. Antibiotics were prescribed in
      76 of 255 (30%) cases. Prescription was assessed as inappropriate in 56 of 76
      (74%) of all cases; in 41 of 52 (79%) cases with acute respiratory infection, in
      none of the pneumonia cases, and in all 15 cases of diarrhoea. Oral rehydration
      salts were prescribed in 74 (87%) of the diarrhoea cases. CONCLUSIONS: Health
      care providers' adherence to guidelines on history taking was suboptimal in acute
      respiratory infection and diarrhoea but poor on examination in both conditions. A
      high level of inappropriate antibiotic prescription was found in acute
      respiratory infection and diarrhoea. Overall, there is considerable scope for
      improving diagnostic and therapeutic management of these major childhood diseases
      in Botswana primary health care.

PMID- 15723819
TI  - The role of the print media in informing the community about safety in public
      hospitals in Victoria, Australia: the case of "golden staph".
AB  - OBJECTIVE: In this article the authors explore how the print media contribute to
      information and education of the community on issues of safety and quality in the
      health services, since this is an important avenue of such information and
      education for many members of the community. STUDY DESIGN: The authors undertook
      a qualitative study of a random sample of articles in the Australian print press
      between 1996 and 2004 where "golden staph" was presented as a major issue of risk
      to the safety of consumers of health services. The content of each article was
      examined with reference to several criteria including title, the source of the
      article, and the metaphorical language employed by the journalist. RESULTS:
      Results show that while the articles are substantially accurate as sources of
      information on concrete events, they do not serve as sources of education on
      issues of safety, typically apportioning blame and serving to maintain the status
      quo. CONCLUSION: The authors conclude that print media are not a good source of
      community education in areas of safety and quality and do not assist members of
      the community to participate in addressing issues of safety in health services.

PMID- 15723820
TI  - Setting national priorities for quality assessment of health care services in
      Korea.
AB  - OBJECTIVE: To identify target services and determine national priorities among
      those services identified for a national quality assessment program of the Health
      Insurance Review Agency (HIRA) in Korea. DESIGN: Target services were identified
      from published sources addressing quality problems, various quality-monitoring
      programs in other countries, suggestions from 26 medical specialty associations
      in Korea, and frequently reported consumer claims. Three steps were involved in
      the prioritization decision: (i) development of a set of priority criteria; (ii)
      expert panel survey to evaluate the extent to which individual services satisfy
      each of the priority criteria and to calculate mean priority ratings for
      individual services; and (iii) formation of four levels of priority groups-top,
      high-middle, middle, and low-according to the allocated priority ratings.
      RESULTS: Five priority criteria were selected: "burden of the condition",
      "seriousness of the quality problem", "interest and demand of society",
      "acceptability", and "the feasibility of quality assessment". Among the 57
      services identified as targets for the national quality assessment program, 10
      were selected as having a top priority for quality assessment because of their
      high feasibility rating. These are: cardiac surgery; cataract surgery;
      tonsillectomy; appendectomy; tooth extraction; usage of albumin/globulin
      products; treatments for hypertension, pneumonia, and acute upper respiratory
      infection; and services provided by clinical laboratory centers. CONCLUSION: The
      priority services identified from the studies will assist the HIRA in selecting
      target services and implementing the national assessment program.

PMID- 15723821
TI  - Frequency of patient-physician contact in chronic kidney disease care and
      achievement of clinical performance targets.
AB  - OBJECTIVE: To examine whether the frequency of physician contact is associated
      with accepted quality of care measures reflecting clinical performance in chronic
      kidney disease patients. DESIGN: Prospective cohort study of end-stage renal
      disease patients begun in 1995, followed for 2.5 years. SETTING: 76 not-for
      profit US dialysis clinics. STUDY PARTICIPANTS: 678 incident hemodialysis
      patients for whom we had information on average frequency of patient-physician
      contact at each clinic (low, monthly or less frequent; intermediate, between
      monthly and weekly; high, more than weekly), determined by clinic survey. MAIN
      OUTCOME MEASURES: Achievement of accepted 6 month clinical performance targets of
      albumin (> or =3.5 g/dl), calcium-phosphate (Ca-P) product (<60 mg(2)/dl(2)),
      dialysis dose (Kt/V > or = 1.2), vascular access type (fistula), and hemoglobin
      (> or =11 g/dl). RESULTS: By logistic regression, patients treated at clinics
      reporting less frequent physician contact had lower odds of achieving most
      targets, statistically significantly for albumin [low, adjusted odds ratio (OR) =
      0.83, 95% confidence interval (CI), 0.55-1.25; intermediate, adjusted OR = 0.62,
      95% CI, 0.42-0.93; reference, high] and dialysis dose (low, adjusted OR = 0.26,
      95% CI, 0.08-0.89; intermediate, adjusted OR = 0.67, 95% CI, 0.20-2.27); however,
      they had greater odds of achieving the hemoglobin target (low, adjusted OR =
      1.94, 95% CI, 1.24-3.04; intermediate, adjusted OR = 1.89, 95% CI, 1.27-2.83).
      Additionally, the number of targets reached was statistically significantly lower
      in the monthly or less group (adjusted OR = 0.43, 95% CI, 0.20-0.94).
      CONCLUSIONS: More frequent patient-physician contact is positively associated
      with the achievement of clinical performance targets in chronic kidney disease
      care.

PMID- 15723822
TI  - Characterization of antifreeze activity in Antarctic plants.
AB  - Deschampsia antarctica and Colobanthus quitensis are the only vascular plants to
      have colonized the Maritime Antarctic, which is characterized by its permanently
      low temperature and frequent summer frosts. To understand how the plants survive
      freezing temperatures year-round, antifreeze activity was assayed in apoplastic
      extracts obtained from both non-acclimated and cold-acclimated Antarctic plants.
      By observing the shape of ice crystals grown in dilution series of the extracts,
      it was found that D. antarctica had antifreeze activity, but C. quitensis did
      not. D. antarctica exhibited antifreeze activity in the non-acclimated state and
      this activity increased after cold acclimation. The antifreeze activity in D.
      antarctica was labile to proteolysis and high temperature, active over a wide pH
      range, and associated with molecules greater than 10 kDa in molecular weight.
      These results show that D. antarctica produces antifreeze proteins that are
      secreted into the apoplast. When examined by SDS-PAGE, the apoplastic extracts
      from cold-acclimated D. antarctica exhibited 13 polypeptides. It is concluded
      that D. antarctica accumulates AFPs as part of its mechanism of freezing
      tolerance. Moreover, this is the first plant in which antifreeze activity has
      been observed to be constitutive.

PMID- 15723823
TI  - Molecular characterization of DNA sequences from the Primula vulgaris S-locus.
AB  - Primula species provide possibly the best known examples of heteromorphic flower
      development and this breeding system has attracted considerable attention,
      including that of Charles Darwin. However, despite considerable recent advances
      in molecular genetics, nothing is known about the molecular basis of floral
      heteromorphy. The first molecular marker for the Primula S-locus is reported
      here. This DNA sequence was identified by random amplification of polymorphic DNA
      (RAPD)-PCR, further defined as a sequence characterized amplified region (SCAR)
      marker, and subsequently shown to correspond to a restriction fragment length
      polymorphism (RFLP) that is linked to the thrum allele of the Primula S-locus.
      The sequence of 8.8 kb of genomic DNA encompassing this thrum-specific RFLP is
      presented. Analysis of this DNA reveals a highly repetitive sequence structure
      similar to that found at the S-locus in other species; it also contains sequences
      similar to elements of a Gypsy-like retrotransposon. The identification of a
      specific DNA sequence associated with the thrum allele of the Primula S-locus
      provides the first molecular probe with which to investigate the molecular basis
      of heteromorphic flower development in Primula.

PMID- 15723824
TI  - Effects of cor15a-IPT gene expression on leaf senescence in transgenic Petunia x
      hybrida and Dendranthema x grandiflorum.
AB  - To prevent leaf senescence of young transplants or excised shoots during storage
      under dark and cold conditions, the cytokinin biosynthetic gene isopentenyl
      transferase (ipt) was placed under the control of a cold-inducible promoter
      cor15a from Arabidopsis thaliana and introduced into Petunia x hybrida 'Marco
      Polo Odyssey' and Dendranthema x grandiflorum (chrysanthemum) 'Iridon'.
      Transgenic cor15a-ipt petunia and chrysanthemum plants and excised leaves
      remained green and healthy during prolonged dark storage (4 weeks at 25 degrees
      C) after an initial exposure to a brief cold-induction period (4 degrees C for 72
      h). However, cor15a-ipt chrysanthemum plants and excised leaves that were not
      exposed to a cold-induction period, senesced under the same dark storage
      conditions. Regardless of cold-induction treatment, leaves and plants of non
      transformed plants senesced under prolonged dark storage. Analysis of ipt
      expression indicated a marked increase in gene expression in intact transgenic
      plants as well as in isolated transgenic leaves exposed to a short cold-induction
      treatment prior to dark storage. These changes correlated with elevated
      concentrations of cytokinins in transgenic leaves after cold treatment. Cor15a
      ipt transgenic plants showed a normal phenotype when grown at 25 degrees C.

PMID- 15723825
TI  - Mapping of quantitative trait loci associated with chilling tolerance in maize
      (Zea mays L.) seedlings grown under field conditions.
AB  - The effect of low growth temperature on morpho-physiological traits of maize was
      investigated by the means of a QTL analysis in a segregating F(2:3) population
      grown under field conditions in Switzerland. Chlorophyll fluorescence parameters,
      leaf greenness, leaf area, shoot dry weight, and shoot nitrogen content were
      investigated at the seedling stage for two years. Maize was sown on two dates in
      each year; thus, plants sown early were exposed to low temperature, whereas those
      sown later developed under more favourable conditions. The main QTLs involved in
      the functioning of the photosynthetic apparatus at low temperature were stable
      across the cold environments and were also identified under controlled conditions
      with suboptimal temperature in a previous study. Based on the QTL analysis,
      relationships between chlorophyll fluorescence parameters and leaf greenness were
      moderate. This indicates that the extent and functioning of the photosynthetic
      machinery may be under different genetic control. The functioning of the
      photosynthetic apparatus in plants developed at low temperature in the field did
      not noticeably affect biomass accumulation; since there were no co-locations
      between QTLs for leaf area and shoot dry weight, biomass accumulation did not
      seem to be carbon-limited at the seedling stage under cool conditions in the
      field.

PMID- 15723826
TI  - Endogenous hormones and expression of senescence-related genes in different
      senescent types of maize.
AB  - Levels of cytokinins and abscisic acid (ABA) and the expression of senescence
      related genes were investigated in two maize (Zea mays L.) cultivars of different
      senescence type, cv. P3845 (stay-green) and cv. Hokkou 55 (earlier senescent), in
      a field study. The delay in leaf senescence in P3845 was correlated with
      increased levels of chlorophyll and nitrogen and a higher photon-saturated
      photosynthetic rate (P(sat)). Compared with the earlier senescent Hokkou 55,
      P3845 showed enhanced contents of cytokinins (trans-zeatin riboside, t-ZR;
      dihydrozeatin riboside, DHZR; isopentenyladenosine, iPA) and reduced levels of
      ABA in its leaves. In roots, P3845 had increased levels of t-ZR, DHZR, and ABA,
      but decreased concentrations of iPA. It was concluded that a higher rate of
      cytokinin transport from roots to leaves contributes to the delay of senescence
      in P3845. By contrast, the translocation of ABA from roots to shoots may be
      blocked in the stay-green cultivar, which also results in retarded leaf
      senescence. P3845 ear leaves contained more malondialdehyde (MDA) and higher
      catalase (CAT) and superoxide dismutase (SOD) activities than Hokkou 55. Since
      the accumulation of the mRNAs for Rubisco small subunit (rbcS),
      phosphoenolpyruvate carboxylase (PEPC), and SOD peaked after Chl content and
      P(sat) had reached their maxima, it is speculated that when leaf senescence is
      initiated, Chl contents decrease first, followed by the degradation of the
      photosynthetic apparatus and of photosynthesis-related enzymes. See1 and See2
      encode senescence-related cysteine proteases; their mRNAs were most abundant in
      yellowing leaves, suggesting that these proteins are involved in the process of
      senescence rather than its initiation. mRNAs of both genes were more abundant in
      Hokkou 55 than in P3845, which suggests a regulation of leaf senescence at the
      transcriptional level.

PMID- 15723827
TI  - Expression of arginine decarboxylase and ornithine decarboxylase genes in apple
      cells and stressed shoots.
AB  - Arginine decarboxylase (ADC) and ornithine decarboxylase (ODC) are two important
      enzymes responsible for putrescine biosynthesis. In this study, a full-length ADC
      cDNA (MdADC) was isolated from apple [Malus sylvestris (L.) Mill. var. domestica
      (Borkh.) Mansf.]. Meanwhile, a partial ODC (pMdODC) could be amplified only by a
      second RCR from the RT-PCR products, whereas a full-length ODC could not be
      obtained by either cDNA library screening or 5'- and 3'-RACEs, suggesting quite
      low expression. Moreover, D-arginine, an ADC inhibitor, caused a decrease in ADC
      activity and severely inhibited the growth of apple callus, which could be
      partially resumed by exogenous addition of putrescine, whereas alpha
      difluoromethylornithine (DFMO), an inhibitor for ODC, caused the incomplete
      repression of callus growth without changing ODC activity. RNA gel blot showed
      that the expression level of MdADC was high in young tissues/organs with rapid
      cell division and was positively induced by chilling, salt, and dehydration,
      implying its involvement in both cell growth and these stress responses. By
      contrast, the transcript of ODC could not be detected by RNA gel blot analysis.
      Based on the present study, it is possible to conclude that (i) the ODC pathway
      is active in apple, although the expression level of the pMdODC gene homologous
      with its counterparts found in other plant species is quite low; and (ii) MdADC
      expression correlates with cell growth and stress responses to chilling, salt,
      and dehydration, suggesting that ADC is a primary biosynthetic pathway for
      putrescine biosynthesis in apple.

PMID- 15723828
TI  - Genes encoding ADP-ribosylation factors in Arabidopsis thaliana L. Heyn.; genome
      analysis and antisense suppression.
AB  - Vesicle trafficking delivers proteins to intracellular and extracellular
      compartments, cellulose synthase to the plasma membrane, and non-cellulosic
      polysaccharides to the cell wall. The Arabidopsis genome potentially encodes 19
      proteins with sequence similarities to ARFs (ADP-ribosylation factors) and its
      relatives such as ARLs (ARF-like proteins). ARFs are essential for vesicle
      coating and uncoating in all eukaryotic cells, while ARLs play more diverse
      roles. Nine proteins, six of them highly similar, are possible ARFs, three are
      putative ARL orthologues and the remainder were designated ARF-related proteins.
      The functions of the six highly similar, putative ARFs in whole plant development
      were probed by suppressing their expression with antisense. Antisense plants were
      severely stunted because cell production rate and final cell size were both
      reduced. Changed time-to-flowering, apical dominance, and fertility may reflect
      alterations to hormonal and other signalling pathways with which ARFs may
      interact. No gross changes in targeting or compartmentalization were seen in
      antisense plants containing GFP targeted to the ER and Golgi and changes in cell
      wall composition were limited to increases in some non-cellulosic polysaccharides
      and a relatively small decrease in cellulose. The reasons why these effects are
      less drastic than the effects on endomembranes and wall composition that are seen
      in short-term experiments with brefeldin A and with dominant negative ARF mutants
      are discussed.

PMID- 15723829
TI  - Exogenous gibberellins inhibit coffee (Coffea arabica cv. Rubi) seed germination
      and cause cell death in the embryo.
AB  - The mechanism of inhibition of coffee (Coffea arabica cv. Rubi) seed germination
      by exogenous gibberellins (GAs) and the requirement of germination for endogenous
      GA were studied. Exogenous GA(4+7) inhibited coffee seed germination. The
      response to GA(4+7) showed two sensitivity thresholds: a lower one between 0 and
      1 microM and a higher one between 10 and 100 microM. However, radicle protrusion
      in coffee seed depended on the de novo synthesis of GAs. Endogenous GAs were
      required for embryo cell elongation and endosperm cap weakening. Incubation of
      coffee seed in exogenous GA(4+7) led to loss of embryo viability and dead cells
      were observed by low temperature scanning microscopy only when the endosperm was
      surrounding the embryo. The results described here indicate that the inhibition
      of germination by exogenous GAs is caused by factors that are released from the
      endosperm during or after its weakening, causing cell death in the embryo and
      leading to inhibition of radicle protrusion.

PMID- 15723831
TI  - NF{kappa}B-dependent down-regulation of tumor necrosis factor receptor-associated
      proteins contributes to interleukin-1-mediated enhancement of ultraviolet B
      induced apoptosis.
AB  - Activation of the transcription factor nuclear factor-kappaB (NFkappaB) by
      inflammatory cytokines like tumor necrosis (TNF) factor and interleukin-1 (IL-1)
      is generally associated with the induction of antiapoptotic pathways. Therefore,
      NFkappaB inhibits both intrinsically and extrinsically induced apoptosis and thus
      is regarded to act universally in an antiapoptotic fashion. Accordingly,
      activation of NFkappaB by IL-1 was shown to result in reduction of death ligand
      induced apoptosis via up-regulation of antiapoptotic inhibitor of apoptosis
      proteins (IAPs). In contrast, apoptosis induced by ultraviolet-B radiation (UVB)
      was shown to be enhanced in an NFkappaB-dependent manner, indicating that
      NFkappaB can also act in a proapoptotic fashion. This study investigates the
      molecular mechanisms underlying IL-1-mediated enhancement of UVB-induced
      apoptosis. We show that NFkappaB activation in costimulation with UVB treatment
      results in repression of antiapoptotic genes and consequently in down-regulation
      of the respective proteins, like c-IAP, FLICE-inhibitory protein (FLIP), and some
      members of the TNF receptor-associated (TRAF)2 protein family. In parallel,
      TNFalpha is released, leading to activation of signaling pathways mediated by TNF
      receptor-1 (TNF-R1). Although TNF is well known to induce both proapoptotic and
      antiapoptotic effects, the down-regulated levels of TRAF-1, -2, and -6 proteins
      by IL-1 plus UVB action leads to a shift toward promotion of the proapoptotic
      pathway. In concert with the down-regulation of IAPs and FLIP, TNF-R1 activation
      as an additional proapoptotic stimulus now results in significant enhancement of
      UVB-induced apoptosis. Taken together, elucidation of the molecular mechanisms
      underlying IL-1-mediated enhancement of UVB-induced apoptosis revealed that
      NFkappaB does not exclusively act in an antiapoptotic fashion but may also
      mediate proapoptotic effects.

PMID- 15723830
TI  - Identification of protein kinase A catalytic subunit beta as a novel binding
      partner of p73 and regulation of p73 function.
AB  - Post-translational modifications play a crucial role in regulation of the protein
      stability and pro-apoptotic function of p53 as well as its close relative p73.
      Using a yeast two-hybrid screening based on the Sos recruitment system, we
      identified protein kinase A catalytic subunit beta (PKA-Cbeta) as a novel binding
      partner of p73. Co-immunoprecipitation and glutathione S-transferase pull-down
      assays revealed that p73alpha associated with PKA-Cbeta in mammalian cells and
      that their interaction was mediated by both the N- and C-terminal regions of
      p73alpha. In contrast, p53 failed to bind to PKA-Cbeta. In vitro phosphorylation
      assay demonstrated that glutathione S-transferase-p73alpha-(1-130), which has one
      putative PKA phosphorylation site, was phosphorylated by PKA. Enforced expression
      of PKA-Cbeta resulted in significant inhibition of the transactivation function
      and pro-apoptotic activity of p73alpha, whereas a kinase-deficient mutant of PKA
      Cbeta had no detectable effect. Consistent with this notion, treatment with H-89
      (an ATP analog that functions as a PKA inhibitor) reversed the dibutyryl cAMP
      mediated inhibition of p73alpha. Of particular interest, PKA-Cbeta facilitated
      the intramolecular interaction of p73alpha, thereby masking the N-terminal
      transactivation domain with the C-terminal inhibitory domain. Thus, our findings
      indicate a PKA-Cbeta-mediated inhibitory mechanism of p73 function.

PMID- 15723832
TI  - TorD, an essential chaperone for TorA molybdoenzyme maturation at high
      temperature.
AB  - TorD has been recognized as an accessory protein that improves maturation of
      TorA, the molybdenum cofactor-containing trimethylamine oxide reductase of
      Escherichia coli. In this study, we show that at 42 degrees C and in the absence
      of TorD TorA is poorly matured and almost completely degraded. Strikingly, TorD
      restores TorA maturation to the same level whatever the growth temperature. In
      vitro experiments in which apoTorA was incubated with or without TorD at various
      temperatures confirm that TorD is an essential chaperone for TorA at elevated
      temperatures preventing apoTorA mis-folding before cofactor insertion.

PMID- 15723833
TI  - The LHbeta gene of several mammals embeds a carboxyl-terminal peptide-like
      sequence revealing a critical role for mucin oligosaccharides in the evolution of
      lutropin to chorionic gonadotropin in the animal phyla.
AB  - The expression of a previously untranslated carboxylterminal sequence is
      associated with the ancestral lutropin (LH) beta to the beta-subunit gene
      evolution of choriogonadotropins (CG). The peptide extension (denoted as CTP) is
      rich in mucin-type O-glycans and confers new hormonal properties on CG relative
      to the LH. Although the LHbeta gene is conserved among mammals and only a few
      frameshift mutations account for the extension, it is merely seen in primates and
      equids. Bioinformatics identified a CTP-like sequence that is encrypted in the
      LHbeta gene of several mammalian species but not in birds, amphibians, or fish.
      We then examined whether or not decoding of the cryptic CTP in the bovine LHbeta
      gene (boCTP) would be sufficient to generate the LHbeta species of a ruminant
      with properties typical to the CGbeta subunit. The mutated bovine LHbeta-boCTP
      subunit was expressed and N-glycosylated in transfected Chinese hamster ovary
      cells. However, unlike human (h) CGbeta CTP, the cryptic boCTP was devoid of
      mucin O-glycans. This deficiency was further confirmed when the boCTP domain was
      substituted for the natural CTP in the human CGbeta subunit. Moreover, when
      expressed in polarized Madin-Darby canine kidney cells, this hCGbeta-boCTP
      chimera was secreted basolaterally rather than from the apical compartment, which
      is the route of the wild type hCGbeta subunit, a sorting function attributed to
      the O-glycans attached to the CTP. This result shows that the cryptic peptide
      does not orientate CG to the apical face of the placenta, to the maternal
      circulation as seen in primates. The absence of this function, which
      distinguishes CG from LH, provides an explanation as to why the LHbeta to CGbeta
      evolution did not occur in ruminants. We propose that in primates and equids,
      further natural mutations in the progenitor LHbeta gene resulted in the efficient
      O-glycosylation of the CTP, thus favoring the retention of an elongated reading
      frame.

PMID- 15723834
TI  - Identification and characterization of the unique N-linked glycan common to the
      flagellins and S-layer glycoprotein of Methanococcus voltae.
AB  - The flagellum of Methanococcus voltae is composed of four structural flagellin
      proteins FlaA, FlaB1, FlaB2, and FlaB3. These proteins possess a total of 15
      potential N-linked sequons (NX(S/T)) and show a mass shift on an SDS
      polyacrylamide gel indicating significant post-translational modification. We
      describe here the structural characterization of the flagellin glycan from M.
      voltae using mass spectrometry to examine the proteolytic digests of the
      flagellin proteins in combination with NMR analysis of the purified glycan using
      a sensitive, cryogenically cooled probe. Nano-liquid chromatography-tandem mass
      spectrometry analysis of the proteolytic digests of the flagellin proteins
      revealed that they are post-translationally modified with a novel N-linked
      trisaccharide of mass 779 Da that is composed of three sugar residues with masses
      of 318, 258, and 203 Da, respectively. In every instance the glycan is attached
      to the peptide through the asparagine residue of a typical N-linked sequon. The
      glycan modification has been observed on 14 of the 15 sequon sites present on the
      four flagellin structural proteins. The novel glycan structure elucidated by NMR
      analysis was shown to be a trisaccharide composed of beta-ManpNAcA6Thr-(1-4)-beta
      Glc-pNAc3NAcA-(1-3)-beta-GlcpNAc linked to Asn. In addition, the same
      trisaccharide was identified on a tryptic peptide of the S-layer protein from
      this organism implicating a common N-linked glycosylation pathway.

PMID- 15723835
TI  - A yeast polyamine acetyltransferase.
AB  - An uncharacterized yeast gene has been shown to encode a polyamine
      acetyltransferase and named PAA1. The recombinant Paa1 protein readily acetylates
      various polyamines such as putrescine, spermidine, and spermine. paa1 mutants are
      viable and grow normally under standard conditions. The mutants are sensitive to
      hydroxyurea, and they are synthetically temperature-sensitive with a rad53-21
      mutation. The mutants also show genetic interactions with components of the
      transcriptional co-activator complex, SAGA, and partially suppress Spt-
      phenotypes of two spt mutants. These phenotypes suggest that acetylation of
      polyamines removes them from chromatin and makes the chromatin more accessible.
      It is known that spermine, but not acetyl spermine, is a precursor in the pathway
      for synthesis of coenzyme A in yeast. When Paa1 is overexpressed, leading to a
      lower level of spermine, cells show a growth dependence on either of two
      downstream compounds in the coenzyme A pathway, pantothenate or beta-alanine.
      This demonstrates that spermine and perhaps other polyamines are the in vivo
      targets of Paa1.

PMID- 15723836
TI  - Neuroligins mediate excitatory and inhibitory synapse formation: involvement of
      PSD-95 and neurexin-1beta in neuroligin-induced synaptic specificity.
AB  - The balance between excitatory and inhibitory synapses is a tightly regulated
      process that requires differential recruitment of proteins that dictate the
      specificity of newly formed contacts. However, factors that control this process
      remain unidentified. Here we show that members of the neuroligin (NLG) family,
      including NLG1, NLG2, and NLG3, drive the formation of both excitatory and
      inhibitory presynaptic contacts. The enrichment of endogenous NLG1 at excitatory
      contacts and NLG2 at inhibitory synapses supports an important in vivo role for
      these proteins in the development of both types of contacts. Immunocytochemical
      and electrophysiological analysis showed that the effects on excitatory and
      inhibitory synapses can be blocked by treatment with a fusion protein containing
      the extracellular domain of neurexin-1beta. We also found that overexpression of
      PSD-95, a postsynaptic binding partner of NLGs, resulted in a shift in the
      distribution of NLG2 from inhibitory to excitatory synapses. These findings
      reveal a critical role for NLGs and their synaptic partners in controlling the
      number of inhibitory and excitatory synapses. Furthermore, relative levels of PSD
      95 alter the ratio of excitatory to inhibitory synaptic contacts by sequestering
      members of the NLG family to excitatory synapses.

PMID- 15723837
TI  - MEK-ERK signaling controls Hdm2 oncoprotein expression by regulating hdm2 mRNA
      export to the cytoplasm.
AB  - The physical and functional interaction between the transcription factor p53 and
      its negative regulatory partner protein Hdm2 (Mdm2 in mouse) is a key point of
      convergence of multiple signaling pathways that regulates cell proliferation and
      survival. hdm2 mRNA transcription is induced by p53, forming the basis of an auto
      regulatory feedback loop. Growth and survival factor-activated Ras-Raf-MEK-ERK
      signaling can also regulate Hdm2 expression independently of p53, contributing to
      the pro-survival effect of these factors. In murine fibroblasts, this occurs
      through the regulation of mdm2 mRNA transcription. Here we show that, in human
      breast cancer epithelial cells, MEK-dependent regulation of Hdm2 expression also
      occurs at a post-transcriptional level. Pharmacological blockade of MEK activity
      in T47D cells inhibits Hdm2 protein synthesis by 80-90%. This occurs in the
      absence of changes in the expression of the major hdm2-P1 mRNA transcript and
      only an approximately 40% reduction in hdm2-P2 transcript levels. The amounts of
      both transcripts that are associated with polyribosomes and are, hence, being
      actively translated are reduced by >80% by the MEK inhibitor, U0126. We show here
      that this is due to the inhibition of hdm2 mRNA export from the nucleus when MEK
      activity is inhibited. In MCF-7 breast cancer cells that express wild-type p53,
      Hdm2 is required to suppress p53-dependent transcription when MEK kinase is
      active. Regulation of the nuclear export of hdm2 mRNA provides, therefore, a
      mechanism whereby mitogen-stimulated cells avoid p53-dependent cell cycle arrest
      or apoptosis by maintaining the dynamic equilibrium of the Hdm2-p53 feedback
      loop.

PMID- 15723838
TI  - The complexity of a "complex mass" and the simplicity of a "simple cyst".

PMID- 15723839
TI  - D. Eugene Strandness, Jr, MD, and the revolution in noninvasive vascular
      diagnosis: part 1: foundations.

PMID- 15723840
TI  - Evaluation using contrast-enhanced harmonic gray scale sonography after radio
      frequency ablation of small hepatocellular carcinoma: sonographic-histopathologic
      correlation.
AB  - OBJECTIVE: To evaluate the usefulness of contrast-enhanced harmonic wideband gray
      scale sonographic images obtained after radio frequency-induced coagulation
      necrosis, we compared the morphologic and histopathologic characteristics of the
      ablated tumors with sonographic images of the tumors. METHODS: Forty-eight
      patients with 72 hepatocellular carcinomas with a maximal diameter of 3 cm or
      less were treated percutaneously using radio frequency ablation. Six treated
      tumors in 4 patients were resected 1 month after ablation; the remaining 66
      treated tumors were evaluated by a biopsy procedure performed with an 18-gauge
      fine needle 1 month after ablation. The excised tumors and biopsy specimens were
      then examined by histopathologic methods, and the findings were compared with
      those obtained on contrast-enhanced harmonic wideband gray scale sonography.
      Hematoxylin-eosin-stained specimens were inconclusive as to whether cellular
      viability remained; therefore, cell viability was determined by a positive result
      after histochemical (lactate dehydrogenase and nicotinamide adenine dinucleotide
      phosphate-diaphorase) staining. RESULTS: Contrast-enhanced harmonic wideband gray
      scale sonography after radio frequency ablation showed residual tumor enhancement
      in 5 (6.9%) of the 72 tumors; the histopathologic results for these 5 tumors were
      also positive for tumor residue. The remaining 67 tumors (93.1%) did not show any
      residual tumor enhancement when examined by sonography; however, only 66 tumors
      did not reveal tumor residue when examined histopathologically. Contrast-enhanced
      harmonic wideband sonographic imaging provided results that were comparable with
      histopathologic findings, the criterion standard for diagnosis; the sensitivity
      and specificity of the sonographic images for the detection of residual tumor
      tissue in ablated tumors were 83.3% (5 of 6) and 100% (66 of 66), respectively.
      CONCLUSIONS: Contrast-enhanced harmonic wideband gray scale sonography is a
      potentially useful technique for evaluating the therapeutic effects of radio
      frequency ablation on hepatocellular carcinoma.

PMID- 15723841
TI  - Imaging of focal liver lesions: low-mechanical-index real-time ultrasonography
      with SonoVue.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of a contrast
      enhanced contrast-specific ultrasonographic technique with a low mechanical index
      for characterization of focal liver lesions. METHODS: Contrast-specific
      ultrasonography was used to assess 144 patients with 147 focal liver lesions: 87
      primary liver carcinomas, 27 hemangiomas, 16 focal nodular hyperplasias, 5
      hepatic abscesses, 3 inflammatory pseudotumors of the liver, and 9 metastases. A
      sulfur hexafluoride gas-based contrast agent was used with a mechanical index of
      0.08 to 0.11. RESULTS: On contrast-enhanced ultrasonography, the typical
      hemodynamic pattern of primary liver carcinoma was the whole-lesion enhancement
      or mosaic enhancement in the arterial phase with an enhancement defect in the
      late phase (sensitivity, 92.0%; specificity, 86.7%). The most common enhancement
      pattern of hemangioma was that enhancement appeared in the periphery first and
      progressively filled into the lesion center (sensitivity, 96.3%; specificity,
      97.5%). The enhancement pattern of focal nodular hyperplasia was that the whole
      lesion enhanced early and rapidly in the arterial phase with a centrifugal
      radiating configuration and appeared isoechoic or hyperechoic until the late
      phase (sensitivity, 87.6%; specificity, 94.5%). The central scar was detected in
      31.3% of cases in the late phase. The specific enhancement of a hepatic abscess
      was the honeycomblike enhancement in all phases (sensitivity, 80.0%; specificity,
      100%). No enhancement of a lesion in all phases was specific for an inflammatory
      pseudotumor of the liver. CONCLUSIONS: Contrast-enhanced real-time
      ultrasonography is a promising approach in the noninvasive characterization of
      focal liver lesions and can be useful as a first-line imaging technique
      clinically when a focal liver lesion is detectable on ultrasonography.

PMID- 15723842
TI  - Blunt hepatic trauma: evaluation with contrast-enhanced sonography: sonographic
      findings and clinical application.
AB  - OBJECTIVE: The purpose of this study was to report our initial experience in the
      assessment of liver trauma with real-time contrast-enhanced sonography (CES).
      METHODS: From January 2000 to December 2003, there were 431 hemodynamically
      stable patients evaluated with sonography for blunt abdominal trauma. Among these
      patients, 87 were selected to undergo second-level imaging, consisting of CES and
      computed tomographic (CT) evaluation. Indications for further assessment were
      baseline sonographic findings positive for liver injury, baseline sonographic
      findings positive for injury to other abdominal parenchyma, baseline sonographic
      findings positive for free fluid only, baseline sonographic findings
      indeterminate, and baseline sonographic findings negative with persistent
      clinical or laboratory suspicion. RESULTS: There were 23 hepatic lesions shown by
      CT in 21 patients. Peritoneal or retroperitoneal fluid was identified in 19 of 21
      positive cases by all 3 imaging modalities. Liver injury was found in 15 patients
      on sonography and in 19 on CES. Contrast-enhanced sonography compared better than
      unenhanced sonography with the criterion standard for related injury conspicuity,
      injury size, completeness of injury extension, and involvement of the liver
      capsule. Both CES and CT showed intrahepatic contrast material pooling in 2
      cases. All patients with false-negative sonographic or CES findings recovered
      uneventfully. CONCLUSIONS: Contrast-enhanced sonography is an effective tool in
      the evaluation of blunt hepatic trauma, being more sensitive than baseline
      sonography and correlating better than baseline sonography with CT findings. In
      institutions where sonography is regarded as the initial procedure to screen
      patients with trauma, this technique may increase its effectiveness. In addition,
      CES may be valuable in the follow-up of patients with conservatively treated
      liver trauma.

PMID- 15723843
TI  - Value of Doppler sonography in assessing the progression of chronic viral
      hepatitis and in the diagnosis and grading of cirrhosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the value of Doppler
      sonography in assessing the progression of chronic viral hepatitis and in the
      diagnosis and grading of cirrhosis. METHODS: Abdominal sonographic and liver
      Doppler studies were performed in 3 groups: 36 patients with chronic viral
      hepatitis, 63 patients with cirrhosis, and 30 control subjects with no evidence
      of liver disease. A series of Doppler indices of hepatic vascularity, including
      portal vein velocity, portal vein pulsatility score, flow volume of the portal
      vein, resistive and pulsatility indices of the hepatic artery, modified hepatic
      index, hepatic vascular index, waveform of the hepatic vein, and focal
      acceleration of flow, were measured and correlated with liver and spleen size,
      portal and splenic vein diameter, and presence of ascites and collateral vessels.
      These indices were compared across the 3 study groups and within the patient
      groups with respect to presence of inflammation, fibrosis, and steatosis, as
      determined by histologic evaluation. RESULTS: The most useful indices were portal
      vein velocity, the modified hepatic index, and nontriphasic flow in the hepatic
      vein, which were helpful in distinguishing patients from control subjects.
      Hepatic vascular and modified hepatic indices were useful for differential
      diagnosis of cirrhosis and chronic viral hepatitis. However, all measurements
      were limited in their ability to determine the severity of chronic hepatitis.
      CONCLUSIONS: Doppler sonography is sensitive to hemodynamic alterations resulting
      from inflammation and fibrosis, and if sonography is the study of choice to
      follow the progression of hepatitis, it will not be adequate without Doppler
      imaging. Doppler sonography has high diagnostic accuracy in cirrhosis despite
      some false-positive conditions. However, it has a limited role in clinical
      grading.

PMID- 15723844
TI  - Periappendiceal hyperechoic structure on sonography: a sign of severe
      appendicitis.
AB  - OBJECTIVE: We retrospectively investigated the clinical importance of the
      periappendiceal hyperechoic structure (PHS) using sonography in patients with
      appendicitis, which may reflect the omentum encapsulating the inflammation or
      spread of inflammation over the omental and adjacent mesenteric fat. METHODS: We
      defined the positive finding of a PHS as a noncompressible and enlarged (>6 mm in
      its maximal outer diameter) appendix surrounded by the hyperechoic structure that
      was not visualized in the right lower quadrant on sonography. We compared this
      finding with surgical records and pathologic diagnosis in 25 patients who
      underwent an appendectomy for appendicitis. RESULTS: Of 25 patients, there were 7
      patients with positive PHS findings. The positive PHS rates were 100% (2 of 2),
      29% (5 of 17), and 0% (0 of 6) for gangrenous, phlegmonous, and early
      appendicitis, respectively. There was a statistically significant difference by
      the Spearman rank test. The incidence rates of perforation (57% versus 6%),
      macroscopic purulent exudate or abscess (57% versus 6%), and prominent adhesion
      to the periappendiceal tissue (100% versus 22%) were higher in the patients with
      positive PHS findings. CONCLUSIONS: The PHS may indicate the possibility of
      serious inflammation, and accurate diagnosis and appropriate treatment should be
      decided.

PMID- 15723845
TI  - A small-angled thin edge of the placenta predicts abnormal placentation at
      delivery.
AB  - OBJECTIVE: This study was intended to determine the relationship between the
      angle of the lower placental edge in early pregnancy and the previa/low-lying
      placenta at delivery. METHODS: We used transvaginal sonography to consecutively
      screen 2543 singleton pregnancies. All subjects were scanned during the period of
      gestation between 12 weeks 0 days and 15 weeks 6 days. The angle of the lower
      placental edge was measured when the placenta covered the internal cervical os.
      These cases were followed sonographically until term. RESULTS: Of 168 cases in
      which the internal cervical os was covered at screening, 9 showed previa/low
      lying placenta at delivery (previa/low-lying group). The remaining 159 showed no
      abnormal placentation (nonprevia group). There were significantly fewer degrees
      of angle in the previa/low-lying group than in the nonprevia group (P < .05). For
      the previa/low-lying group, the arithmetic mean, median, and SD values of the
      angles were 60.8 degrees , 50.0 degrees , and 9.8 degrees , respectively. For the
      nonprevia group, those values were 103.4 degrees , 103.0 degrees , and 31.8
      degrees , respectively. Data based on the cutoff number of the angle of 74
      degrees indicated the following: sensitivity of placenta previa or low-lying
      placenta at term, 100% (9 of 9); false-positive rate, 23% (36 of 159); positive
      predictive value, 20% (9 of 45); and negative predictive value, 100% (123 of
      123). CONCLUSIONS: The angle between the placental-uterine interface and fetal
      placental surface can be evaluated during early pregnancy. It appears to
      accurately predict placenta previa or low-lying placenta at term gestation with a
      sensitivity of 100%, a false-positive rate of 23%, and a high negative predictive
      value of 100%, which would allow for elimination of some of the multiple scans.

PMID- 15723846
TI  - Superthreshold behavior of ultrasound-induced lung hemorrhage in adult rats: role
      of pulse repetition frequency and exposure duration revisited.
AB  - OBJECTIVE: The purpose of this study was to augment and reevaluate the ultrasound
      induced lung hemorrhage findings of a previous 5 x 3 factorial design study
      (Ultrasound Med Biol 2001; 27:267-277) that evaluated the role of pulse
      repetition frequency (PRF: 25, 50, 100, 250, and 500 Hz) and exposure duration
      (ED; 5, 10, and 20 s) on ultrasound-induced lung hemorrhage at an in situ (at the
      pleural surface) peak rarefactional pressure [pr(in situ)] of 12.3 MPa; only PRF
      was found to be significant. However, saturation (response plateau) due to the
      high pr(in situ) might have skewed the results. In this follow-up 3 x 3 factorial
      design study, a wider range of PRFs and EDs were used at a lower pr(in situ).
      METHODS: Sprague Dawley rats (n=198) were divided into 18 ultrasonically exposed
      groups (10 rats per group) and 6 sham groups (3 per group). The 3 x 3 factorial
      design study (PRF: 17, 170, and 1700 Hz; ED: 5, 31.6, and 200 s) was conducted at
      2 frequencies (2.8 and 5.6 MHz). The p(r(in situ)) was 6.1 MPa. Logistic
      regression analysis evaluated lesion occurrence, and Gaussian tobit analysis
      evaluated lesion depth and surface area. RESULTS: Frequency did not have a
      significant effect, so the analysis combined results for the 2 frequencies. For
      lesion occurrence and sizes, the main effects for PRF and ED were not
      significant. The interaction term was highly significant, indicating a strong
      dependence of lesion occurrence and size on the total number of pulses (PRF x
      ED). CONCLUSIONS: The results of both studies are consistent with the hypothesis
      that the total number of pulses is an important factor in the genesis of
      ultrasound-induced lung hemorrhage.

PMID- 15723847
TI  - Contrast-aided diagnostic ultrasound does not enhance lung metastasis in a mouse
      melanoma tumor model.
AB  - OBJECTIVE: The purpose of this research was to test the hypothesis that contrast
      aided diagnostic ultrasound (CADUS) could exacerbate the metastatic spread of
      mouse melanoma tumor cells to the lungs. METHODS: The melanoma cell lines B16 and
      B16-D5 (metastatic specifically to lung) were implanted on a hind leg of female
      C57/bl6 mice. Growing tumors were scanned by 1.5-MHz diagnostic ultrasound in a
      37 degrees C water bath. Four hundred image frames were triggered at a 1-Hz rate
      with 4 retro-orbital injections of an ultrasonographic contrast agent at dosage
      of 10 microL/kg at 100-second intervals. Sham-treated mice received 400 frames of
      ultrasonography followed by the contrast agent with the ultrasound off. The
      primary tumor was surgically removed 1 day after ultrasound administration. Lungs
      were removed and evaluated blind after 2 weeks of bleaching in Fekete solution.
      RESULTS: Three experiments were performed. The first experiment involved scanning
      sham and CADUS groups of 20 mice each with B16 tumors; B16 metastasis was not
      enhanced. The second experiment repeated this test with the D5 cell line; the
      metastasis enhancement was marginally significant for average number (0.3 and
      3.2; P = .06) and incidence (3 and 9 of 19; P = .08) in mice without tumor
      recurrence. Finally, a third experiment was performed to clarify ambiguous
      results in the second experiment and consisted of 2 groups of 40 mice each. In
      this larger experiment, the results were essentially equal for the sham and CADUS
      groups. CONCLUSIONS: Overall, the results do not support the hypothesis of CADUS
      enhanced metastasis.

PMID- 15723848
TI  - Impairment of change in diameter of the hepatic portion of the inferior vena
      cava: a sonographic sign of liver fibrosis or cirrhosis.
AB  - OBJECTIVE: We propose a new sonographic technique for detecting parenchymal
      stiffness of the liver. This technique measures the physiologic change in the
      diameter of the hepatic inferior vena cava (IVC). The hepatic portion of the IVC
      is extensively attached to the hepatic parenchyma so that changes in diameter of
      the venous lumen could not occur without changes in the shape of the surrounding
      parenchyma. Therefore, increased parenchymal stiffness due to cirrhosis or
      fibrosis may result in an impaired change in venous diameter. METHODS: Thirty
      patients with histologically proven cirrhosis and 30 patients with normal livers
      were examined. A commercial ultrasound system was used in conjunction with a
      convex probe at a center frequency of 4.0 MHz. The major axis of the IVC was
      measured during normal breathing. The patients were then requested to take a deep
      breath to produce negative intrathoracic pressure, and the same measurement as
      that during normal breathing was repeated immediately. RESULTS: In the normal
      liver group, the maximal diameter of the vena cava was 2.35 +/- 0.34 cm (mean +/-
      SD), and this was reduced by 1.30 +/- 0.67 cm (range, 0.4-2.85 cm) during deep
      inspiration. In the cirrhotic patient group, the maximal diameter was 1.74 +/-
      0.35 cm, and this was reduced by 0.03 +/- 0.09 cm (range, 0.0-0.4 cm) (P <
      .0001). CONCLUSIONS: The physiologic change in the diameter of the hepatic
      portion of the IVC enhanced by deep respiration may reflect the stiffness of
      hepatic parenchyma.

PMID- 15723849
TI  - Assessment of portal vein invasion in pancreatic cancer by fusion 3-dimensional
      ultrasonography.
AB  - OBJECTIVE: The purpose of this study was to assess the usefulness of a newly
      developed imaging technique, fusion 3-dimensional ultrasonography (3DUS) in the
      diagnosis of portal vein (PV) invasion in patients with pancreatic cancer (PC).
      METHODS: Fourteen patients with proven PC were examined by fusion 3DUS presented
      as shaded volume-rendering and multiplanar reconstruction images. The surgical
      findings were obtained in all patients (12 with resection and 2 without). The
      findings were compared with those of 2-dimensional ultrasonography (2DUS),
      contrast-enhanced computed tomography (CT), dynamic CT (DCT), angiography, and
      surgical findings. Portal vein invasion was assessed by 3 independent
      radiologists for each modality, and objectivity of the assessment was examined by
      interobserver variability analysis (kappa value). RESULTS: On the basis of
      surgical findings, the accuracy rates of 2DUS, fusion 3DUS, DCT, and angiography
      were 78.6%, 92.9%, 85.3%, and 66.7%, respectively. The kappa values of 2DUS,
      fusion 3DUS, DCT, and angiography for PV invasion were 0.57, 0.90, 0.63, and
      0.49, respectively, being most objective in fusion 3DUS. CONCLUSIONS: Fusion 3DUS
      is useful for diagnosis of PV invasion of PC.

PMID- 15723850
TI  - How sonographic tomography will change the face of obstetric sonography: a pilot
      study.
AB  - OBJECTIVE: This study was undertaken to determine whether 3-dimensional (3D)
      volume sonography (sonographic tomography) can yield a far quicker and equally
      accurate anatomic examination of the second-trimester fetus compared with
      traditional 2-dimensional (2D) scanning. METHODS: Twenty-five consecutive second
      trimester fetuses with normal structural surveys on standard 2D imaging underwent
      5 standard 3D volume acquisitions each (in the regions of the head, chest,
      abdomen, face, and lower extremities) immediately after the 2D scan. The 2D and
      3D images were subsequently compared in relation to the completeness of the fetal
      survey, measurements of the biparietal diameter and femur length, and time
      required to obtain the fetal survey. RESULTS: The structural surveys were
      complete in 20 of 25 cases using 3D reconstructed volumes. One fetus had an
      incomplete evaluation of the face on 3D volumes (and limited on 2D imaging
      because of the prone position of the fetus). The other 4 fetuses with incomplete
      surveys done on 3D volumes had missing images of a hand or foot. Three
      dimensional reconstructions slightly overmeasured the biparietal diameter
      compared with the 2D reference standard (mean difference, 1.1 mm; P < .001). For
      femur length, the mean difference was not statistically significant. It took a
      mean time of 1.1 minutes to obtain the 3D volumes and 5.5 minutes to reconstruct
      the complete surveys by the 3D volume method. With the standard 2D technique, the
      structural surveys were done in a mean time of 13.9 minutes. The mean time
      difference between both methods was 7.3 minutes (P = 2.4 x 10(-9)). CONCLUSIONS:
      Using 3D volume acquisition, it is feasible to perform and interpret a structural
      survey in half the time in which a 2D survey is performed. Further research is
      necessary to standardize the acquisition of volumes to minimize artifacts and
      produce uniform images.

PMID- 15723851
TI  - Torsion of a wandering spleen associated with portal vein thrombosis.

PMID- 15723852
TI  - A case of portal venous gas secondary to acute appendicitis detected on gray
      scale sonography but not computed tomography.

PMID- 15723853
TI  - Peyronie disease involving the entire tunica albuginea of the penis.

PMID- 15723854
TI  - Intrapericardial extralobar pulmonary sequestration: unusual cause of hydrops
      fetalis.

PMID- 15723855
TI  - Sonographic appearance of previous cesarean scars in pregnant women as 3
      macroscopic types.

PMID- 15723856
TI  - Whither the sonographic practitioner?

PMID- 15723857
TI  - Discovery of LH-regulated genes in the primate corpus luteum.
AB  - Circulating LH is essential for the development and function of the primate
      corpus luteum (CL) during the menstrual cycle. However, the cellular and
      molecular processes whereby LH controls luteal structure and function are poorly
      understood. Therefore, studies were initiated to identify gene products that are
      regulated by gonadotrophin in the monkey CL. Rhesus monkeys either were untreated
      (controls, CTRL; n = 3) or received the GnRH antagonist Antide (ANT; 3 mg/kg body
      weight, n = 3) to inhibit pituitary LH secretion on day 6 of the luteal phase in
      spontaneous menstrual cycles. The CL was removed 24 h later. RNA was extracted
      and converted to cDNA. The CTRL and ANT cDNA were differentially labelled with
      fluorescent dyes (Cy3-CTRL and Cy5-ANT) and hybridized onto microarrays
      containing 11,600 human cDNA. The selected cDNA were analysed further via semi
      quantitative RT-PCR (a) to validate the microarray results and (b) to determine
      if their expression varies in the CL (n = 3/stage) between the mid (day 6-8),
      late (day 14-16), or very late (day 18-19, menses) luteal phase of the natural
      cycle. After normalization of the fluorescence data, 206 cDNA (1.8% of the total)
      exhibited > or = 2-fold change in expression after ANT. Of the 25 cDNA exhibiting
      a > or = 6-fold change, 6 were up-regulated and 19 were down-regulated. Twenty
      two of these 25 cDNA were validated by RT-PCR as differentially expressed in the
      ANT group, relative to the CTRL group, and 11 of 25 changed (P < 0.05)
      correspondingly in the late-to-very late luteal phase. Thus, we have identified
      gene products that are regulated by gonadotrophin in the primate CL that may be
      important in luteal regression during the menstrual cycle.

PMID- 15723858
TI  - Oral and dental aspects of chronic renal failure.
AB  - The present article reviews, in detail, the current knowledge of the oral and
      dental aspects of chronic renal failure (CRF). Worldwide, increasing numbers of
      persons have CRF; thus, oral health care staffs are increasingly likely to
      provide care for patients with such disease. Chronic renal failure can give rise
      to a wide spectrum of oral manifestations, affecting the hard or soft tissues of
      the mouth. The majority of affected individuals have disease that does not
      complicate oral health care; nevertheless, the dental management of such
      individuals does require that the clinician understand the multiple systems that
      can be affected. The clinician should also consider the adverse side-effects of
      drug therapy and appropriate prescribing, in view of compromised renal clearance.

PMID- 15723859
TI  - Behcet's disease: a review.
AB  - Behcet's disease (BD) is a multi-system inflammatory disorder dominated
      clinically by recurrent oral and genital ulceration, uveitis, and erythema
      nodosum. Behcet's disease runs a chronic course, with unpredictable exacerbations
      and remissions whose frequency and severity may diminish with time. Behcet's
      disease typically arises in young adults, although childhood-onset BD has also
      been reported. The disease can affect both genders and has a worldwide
      distribution, although it is more prevalent in countries of the ancient Silk
      Route. The cause of BD remains unknown, although an autoimmune reaction triggered
      by an infectious agent in a genetically predisposed individual has been
      suggested. The treatment of BD is symptomatic and empirical, but generally
      specific to the clinical features of each patient. The majority of affected
      individuals do not have life-threatening disease, although mortality can be
      associated with vascular-thrombotic and neurological disease.

PMID- 15723860
TI  - In vivo fluid movement through dentin adhesives in endodontically treated teeth.
AB  - Fluid transudation through simplified dentin adhesives can occur in bonded vital
      crown dentin, since these adhesives behave as permeable membranes after
      polymerization. The effect of adhesive permeability in endodontically treated
      teeth is unknown. This study examined the hypothesis that in vivo fluid movement
      through simplified adhesives occurs when they are applied to root canals. Dowel
      spaces were prepared in endodontically treated teeth with single root canals. Six
      adhesives were applied to the intra-radicular dentin of canal walls. Impressions
      were obtained with polyvinyl siloxane, and replicas were fabricated with the use
      of polyether impression material. Replica hemisections were gold-coated for SEM
      examination. Fluid transudation was evident on the adhesive surfaces of all
      simplified total-etch and self-etch adhesives. Conversely, most of the specimens
      bonded with the control three-step total-etch adhesive were devoid of fluid
      droplets. Permeability of simplified adhesives results in water movement, even in
      root-treated dentin. This may adversely affect the coupling of auto-/dual-cured
      resin cements.

PMID- 15723861
TI  - Increased apoptosis during morphogenesis of the lower cheek teeth in tabby/EDA
      mice.
AB  - In wild-type (WT) mice, epithelial apoptosis is involved in reducing the
      embryonic tooth number and the mesial delimitation of the first molar. We
      investigated whether apoptosis could also be involved in the reduction of tooth
      number and the determination of anomalous tooth boundaries in tabby (Ta)/EDA
      mice. Using serial histological sections and computer-aided 3D reconstructions,
      we investigated epithelial apoptosis in the lower cheek dentition at embryonic
      days 14.5-17.5. In comparison with WT mice, apoptosis was increased mainly
      mesially in Ta dental epithelium from day 15.5. This apoptosis showed a similar
      mesio-distal extent in all 5 morphotypes (Ia,b,c and IIa,b) of Ta dentition and
      eliminated the first cheek tooth in morphotypes IIa,b. Apoptosis did not appear
      to play any causal role in positioning inter-dental gaps. Analysis of the present
      data suggests that the increased apoptosis in Ta mice is a consequence of
      impaired tooth development caused by a defect in segmentation of dental
      epithelium.

PMID- 15723862
TI  - Expression of protein kinases C betaI, betaII, and VEGF during the
      differentiation of enamel epithelium in tooth development.
AB  - Protein kinase C (PKC) is an important molecule involved in various cell
      function, and mediates induced secretion of vascular endothelial growth factor
      (VEGF). It is hypothesized that PKC and VEGF may be associated with tooth
      development. Using the laser microdissection method and real-time reverse
      transcription-polymerase chain-reaction (RT-PCR), we investigated the expression
      of PKC betaI and betaII, VEGF, and amelogenin (used as a marker of
      differentiation to ameloblasts) in the inner and outer enamel epithelia, stellate
      reticulum, and dental papilla in each stage of the dental germ. We found that the
      expression levels of PKC betaI and betaII were increased in the inner enamel
      epithelium during the early bell stage. In addition, the increased expression
      levels of PKC betaI and betaII were accompanied by increased VEGF expression.
      These results indicate that PKC betaI, betaII, and VEGF are closely associated
      with the differentiation of the inner enamel epithelium to ameloblasts.

PMID- 15723863
TI  - Thiazolidinedione (pioglitazone) blocks P. gingivalis- and F. nucleatum, but not
      E. coli, lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) production in
      adipocytes.
AB  - An elevated level of C-reactive protein (CRP) predicts the future development of
      coronary heart disease. Periodontitis appears to up-regulate CRP. CRP is produced
      by hepatocytes in response to interleukin-6 (IL-6). A major source of IL-6 in
      obese subjects is adipocytes. We hypothesized that lipopolysaccharide (LPS) from
      periodontal pathogens stimulated adipocytes to produce IL-6, and that the
      production was suppressed by the drugs targeted against insulin resistance,
      thiazolidinedione (pioglitazone), since this agent potentially showed an anti
      inflammatory effect. Mouse 3T3-L1 adipocytes were stimulated with E. coli, P.
      gingivalis, and F. nucleatum LPS. The IL-6 concentration in culture supernatants
      was measured. All LPS stimulated adipocytes to produce IL-6. Although
      pioglitazone changed adipocyte appearance from large to small, and completely
      suppressed P. gingivalis and F. nucleatum LPS-induced IL-6 production, E. coli
      LPS-induced IL-6 production was not efficiently blocked. Thus, pioglitazone
      completely blocked periodontal-bacteria-derived LPS-induced IL-6 production in
      adipocytes, a major inducer of CRP.

PMID- 15723864
TI  - Role of occlusal vertical dimension in spindle function.
AB  - Several studies have suggested the jaw-muscle spindle as the receptor responsible
      for regulating and maintaining the occlusal vertical dimension (OVD). However, to
      challenge this assumption, we hypothesized that long-term changes in OVD could
      affect the sensory inputs from jaw-muscle spindles. In this study, we
      investigated changes in masseter muscle spindle function under an increased OVD
      (iOVD) condition. Responses of primary and secondary endings of masseter muscle
      spindles to cyclic sinusoidal stretches were investigated. Twenty barbiturate
      anesthetized female Wistar rats were divided into control and iOVD groups. Rats
      in the iOVD group received a 2.0-mm composite resin build-up to the maxillary
      molars. After iOVD, masseter muscle spindle sensitivity gradually decreased.
      Primary and secondary spindle endings were affected differently. We conclude that
      iOVD caused reduction in masseter muscle spindle sensitivity. This result
      suggests that peripheral sensory plasticity may occur following changes in OVD.
      Such changes may provide a basis for physiological adaptation to clinical
      occlusal adjustments.

PMID- 15723865
TI  - Influence of bitter taste on mastication pattern.
AB  - Mastication is a rhythmic activity that can be modified by peripheral information
      generated in the mouth. To study whether taste cognition could influence the way
      in which a food is broken down in the mouth, subjects masticated firm, sugar
      based gelatine gels with differing concentrations of quinine, up to 1500
      micromol/kg, while electromyography (EMG) of masticatory muscles was recorded.
      Taste intensity and composition of saliva were measured. With increasing quinine
      concentration, the average number of chews for nine subjects decreased from 30 to
      22, and their average clearance time increased from 7 to 14 sec. Quinine
      concentration had no effect on chewing frequency (1.3 Hz) or on the rate of
      salivation (5.5 g/min). Bitterness increased, while acceptability and sweetness
      decreased, with increasing concentration of quinine in the gel and in saliva.
      Taste cognition could therefore modify food breakdown in the mouth.

PMID- 15723866
TI  - Genome-wide linkage analysis of mandibular prognathism in Korean and Japanese
      patients.
AB  - The existence of familial aggregation of mandibular prognathism (MP) suggests
      that genetic components play an important role in its etiology. In this study, a
      genome-wide linkage analysis to identify loci susceptible to MP was conducted
      with 90 affected sibling-pairs in 42 families, comprised of 40 Korean sibling
      pairs and 50 Japanese sibling-pairs. Two non-parametric linkage analyses,
      GENEHUNTER-PLUS and SIBPAL, were applied and detected nominal statistical
      significance of linkage to MP at chromosomes 1p36, 6q25, and 19p13.2. The best
      evidence of linkage was detected near D1S234 (maximum Z(lr) = 2.51, P = 0.0012).
      In addition, evidence of linkage was observed near D6S305 (maximum Z(lr) = 2.23,
      P = 0.025) and D19S884 (maximum Z(lr) = 1.93, P = 0.0089). Identification of the
      susceptible genes in the linkage regions will pave the way for insights into the
      molecular pathways that cause MP, especially overgrowth of the mandible, and may
      lead to the development of novel therapeutic tools.

PMID- 15723867
TI  - Does caries in primary teeth predict enamel defects in permanent teeth? A
      longitudinal study.
AB  - The notion that caries in primary teeth causes developmental defects of enamel in
      permanent teeth has been recently revived. The research objective was to test
      this hypothesis through analysis of data from the Dunedin Multidisciplinary
      Health and Development Study, a longstanding prospective cohort study. The
      maxillary incisors of 663 children were assessed for existing restorations and
      dental caries at age five and for developmental defects of enamel at age nine.
      Where a primary tooth had been carious, the permanent successor was more likely
      to have a demarcated opacity after adjustment for gender, family socio-economic
      status, years of exposure to water fluoridation, trauma to primary teeth, and
      early loss of primary teeth (unadjusted OR = 2.3, 95% CI 1.3, 4.1; adjusted OR =
      2.2, 95% CI 1.1, 4.3). These findings support a time-ordered association between
      dental caries in primary maxillary incisors and demarcated opacities in their
      permanent successors.

PMID- 15723868
TI  - The effect of a bi-annual professional application of APF foam on dental caries
      increment in primary teeth: 24-month clinical trial.
AB  - The purpose of this study was to evaluate the effect of a bi-annual professional
      application of acidulated phosphate fluoride (APF) foam on caries increment in
      the primary dentition over a two-year period in the People's Republic of China.
      In a double-blind, cluster-randomized, placebo-controlled trial, 392 children
      aged 3-4 years from 15 classes were randomly assigned to two groups on a school
      class basis. The experimental group (8 classes) received a bi-annual APF foam
      application, and the control group (7 classes) received the placebo. The mean
      increment of dmfs in the experimental group was 24.2% lower than that in the
      control group (p < 0.05). The significant caries reduction was observed on
      approximal surfaces in the experimental group compared with the control group (p
      < 0.01), but there were no differences on occlusal surfaces (p > 0.05). A bi
      annual professional application of APF foam was effective in reducing the
      increment of dental caries in the primary teeth.

PMID- 15723869
TI  - Short-term effects of intensive periodontal therapy on serum inflammatory markers
      and cholesterol.
AB  - Severe periodontitis has been associated with increased systemic inflammation. In
      a three-arm preliminary randomized trial, we investigated the impact of standard
      (SPT) and intensive periodontal therapy (IPT) on serum inflammatory markers and
      cholesterol levels. Medical and periodontal parameters, C-reactive protein (CRP),
      interleukin-6 (IL-6), total cholesterol, and LDL cholesterol were evaluated in 65
      systemically healthy subjects suffering from severe generalized periodontitis.
      Two months after treatment, both SPT and IPT resulted in significant reductions
      in serum CRP compared with the untreated control (0.5 +/- 0.2 mg/L for SPT, P =
      0.030 and 0.8 +/- 0.2 mg/L for IPT, P = 0.001). Similar results were observed for
      IL-6. Changes in inflammation were independent of age, gender, body mass index,
      and ethnicity, but a significant interaction between cigarette smoking and
      treatment regimen was found. The IPT group also showed a decrease in total and
      LDL cholesterol after 2 months. Analysis of these data indicates that
      periodontitis causes moderate systemic inflammation in systemically healthy
      subjects.

PMID- 15723870
TI  - Periodontal disease and prematurity among non-smoking Sri Lankan women.
AB  - The hypothesis that periodontal disease is associated with pre-term low
      birthweight was tested in a prospective follow-up study of rural prima-gravida
      women (N = 227) who were free of tobacco, alcohol, and drug use. Women with 3rd
      trimester mean probing pocket depths, plaque, and bleeding scores that were
      greater than the median value in the cohort were defined as "exposed". There were
      17 (7.5%) preterm low birthweight singleton deliveries in the cohort (among
      "exposed" = 12%; among "unexposed" = 5.6%; Odds Ratio = 2.3; 95% CI = 0.9-6.3).
      After adjustment for the independent variables, the OR for preterm low
      birthweight in relation to "exposure" was 1.9 (95% CI = 0.7-5.4). Our results are
      only suggestive of an association between periodontal disease and preterm low
      birthweight, perhaps indicating that previously reported associations may have
      been subjected to residual confounding due to tobacco, alcohol, and drug use.

PMID- 15723872
TI  - Statistical power for analyses of changes in randomized controlled trials.
AB  - Randomized controlled trials (RCTs) are widely recommended as the most useful
      study design to generate reliable evidence and guidance to daily practices in
      medicine and dentistry. However, it is not well-known in dental research that
      different statistical methods of data analysis can yield substantial differences
      in study power. In this study, computer simulations are used to explore how using
      different univariate and multivariate statistical methods of analyzing change in
      continuous outcome variables affects study power, and the sample size required
      for RCTs. Results show that, in general, analysis of covariance (ANCOVA) yields
      greater power than other statistical methods in testing the superiority of one
      treatment over another, or in testing the equivalence between two treatments.
      Therefore, ANCOVA should be used in preference to change score or percentage
      change score to reduce type II error rates.

PMID- 15723871
TI  - ENAM mutations in autosomal-dominant amelogenesis imperfecta.
AB  - To date, 4 unique enamelin gene (ENAM) defects have been identified in kindreds
      with amelogenesis imperfecta. To improve our understanding of the roles of
      enamelin in normal enamel formation, and to gain information related to possible
      genotype/phenotype correlations, we have identified 2 ENAM mutations in kindreds
      with hypoplastic ADAI, 1 novel (g.4806A>C, IVS6-2A>C) and 1 previously identified
      (g.8344delG), and have characterized the resulting enamel phenotypes. The IVS6
      2A>C mutation caused a severe enamel phenotype in the proband, exhibiting
      horizontal grooves of severely hypoplastic enamel. The affected mother had
      several shallow hypoplastic horizontal grooves in the lower anterior teeth. In
      the case of the g.8344delG mutation, the phenotype was generalized hypoplastic
      enamel with shallow horizontal grooves in the middle 1/3 of the anterior teeth.
      In general, mutations in the human enamelin gene cause hypoplastic enamel, often
      with horizontal grooves, but the severity of the enamel defects is variable, even
      among individuals with the same mutation.

PMID- 15723873
TI  - Acoustics and psychosocial environment in intensive coronary care.
AB  - BACKGROUND: Stress, strain, and fatigue at the workplace have previously not been
      studied in relation to acoustic conditions. AIMS: To examine the influence of
      different acoustic conditions on the work environment and the staff in a coronary
      critical care unit (CCU). METHOD: Psychosocial work environment data from start
      and end of each individual shift were obtained from three shifts (morning,
      afternoon, and night) for a one-week baseline period and for two four-week
      periods during which either sound reflecting or sound absorbing tiles were
      installed. RESULTS: Reverberation times and speech intelligibility improved
      during the study period when the ceiling tiles were changed from sound reflecting
      tiles to sound absorbing ones of identical appearance. Improved acoustics
      positively affected the work environment; the afternoon shift staff experienced
      significantly lower work demands and reported less pressure and strain.
      CONCLUSIONS: Important gains in the psychosocial work environment of healthcare
      can be achieved by improving room acoustics. The study points to the importance
      of further research on possible effects of acoustics in healthcare on staff
      turnover, quality of patient care, and medical errors.

PMID- 15723874
TI  - Pneumoconiosis after sericite inhalation.
AB  - BACKGROUND: Between 1997 and 1999 three sericite plant workers in Parana, Brazil,
      were diagnosed with pneumoconiosis. AIMS: To investigate and describe the
      radiological, clinical, and pathological changes in miners and millers exposed to
      sericite dust with mineralogical characteristics of inhaled dust. METHODS: The
      working premises were visited to examine the sericite processing and to classify
      the jobs according to make qualitative evaluation. Respirable dust was collected
      and the amount of crystalline silica and particle size distribution were
      measured. Forty four workers were examined by a standard questionnaire for
      respiratory symptoms, spirometry, and chest x ray. Material from an open lung
      biopsy was reviewed for histopathological and mineralogical analysis, together
      with sericite samples from the work site to compare the mineral characteristics
      in lung lesions and work area. RESULTS: Respirable dust contained 4.5-10.0%
      crystalline silica. Particle size distribution showed a heavy burden of very fine
      particles (23-55%) with a mean diameter of <0.5 microm. Mean age of sericite
      miners was 41.0 (11.9) and mean number of years of exposure was 13.5 (10.1). In
      52.3% of workers (23/44), chest radiographs presented a median category of 1/0 or
      above, and 18.2% (8/44) had a reduced FEV1. There was a significant association
      between exposure indices and x ray category. Histological studies of the lung
      biopsy showed lesions compatible with mixed dust fibrosis with no silicotic
      nodules. x Ray diffraction analysis of the lung dust residue and the bulk samples
      collected from work area showed similar mineralogical characteristics. Muscovite
      and kaolinite were the major mineral particle inclusions in the lung. CONCLUSION:
      Exposure to fine sericite particles is associated with the development of
      functional and radiological changes in workers inducing mixed dust lesions, which
      are distinct histologically from silicosis.

PMID- 15723876
TI  - Gulf War illnesses...the story is still alive and well.

PMID- 15723875
TI  - Smoothing is soothing, and splines are fine.

PMID- 15723877
TI  - Exposure assessment in ergonomic epidemiology: is there something specific to the
      assessment of biomechanical exposures?

PMID- 15723878
TI  - Hospitalisations among seafarers on merchant ships.
AB  - AIMS: To study morbidity among active seafarers in the merchant navy in order to
      clarify possible work related morbidity and the morbidity related to work and
      lifestyle where possible preventive measures may be initiated. METHODS: From a
      register in the Danish Maritime Authority a cohort of Danish merchant seafarers
      who had been actively employed at sea in 1995 was identified. For each seafarer,
      information on all employment periods at sea, charge aboard, and ship was
      available. The cohort was linked with the National In-patient Register in
      Denmark. Standardised hospitalisation ratios (SHRs) were calculated for all major
      diagnostic groups using all gainfully employed as reference. RESULTS: Seafarers
      were shown to be inhomogeneous, with significant differences in SHRs for the same
      disease groups between different groups of seafarers depending on charge and ship
      type. SHRs for lifestyle related diseases were high, although rates for acute
      conditions, such as acute myocardial infarction, were low, probably due to
      referral bias, as acute conditions are likely to cause hospitalisation abroad,
      and thus are not included in the study. SHRs for injury and poisoning were high,
      especially for ratings and officers aboard small ships. CONCLUSION: Despite pre
      employment selection, a large proportion of the seafarers constitute a group of
      workers with evidence of poor health probably caused by lifestyle. The subgroups
      with high risk of hospitalisation due to lifestyle related diseases also had an
      increased risk of hospitalisation due to injury and poisoning.

PMID- 15723879
TI  - Total body burden arising from a week's repeated dermal exposure to N,N
      dimethylformamide.
AB  - BACKGROUND: Hazardous chemicals and their metabolites may accumulate in the body
      following repeated airborne exposures and skin contact. AIMS: To estimate the
      contribution of skin absorption to total body burden of N,N-dimethylformamide
      (DMF) across a working week in two groups with similar levels of respiratory
      exposure but dissimilar skin contact. METHODS: Twenty five workers in a synthetic
      leather (SL) factory, 20 in a copper laminate circuit board (CLCB) factory, and
      20 age and sex matched non-DMF exposed subjects, were recruited. Environmental
      monitoring of DMF exposure via respiratory and dermal routes, as well as
      biological monitoring of pre-shift urinary N-methylformamide (U-NMF), were
      performed for five consecutive working days. RESULTS: Environmental and
      biological monitoring showed no detectable exposure in controls. The average
      airborne DMF concentration (geometric mean (GM) 3.98 ppm, geometric standard
      deviation (GSD) 1.91 ppm), was insignificantly lower for SL workers than for CLCB
      workers (GM 4.49, GSD 1.84 ppm). Dermal DMF exposure and U-NMF values, however,
      were significantly higher for SL workers. A significant pattern of linear
      accumulation was found across a five day work cycle for SL workers but not for
      CLCB workers. CONCLUSIONS: Dermal exposure to DMF over five consecutive days of
      occupational exposure can result in the accumulation of a significant DMF body
      burden. The long term exposure response under both repeated and intermittent
      conditions of substantial skin exposure is worthy of note.

PMID- 15723880
TI  - Exposure to welding fumes is associated with acute systemic inflammatory
      responses.
AB  - AIMS: To investigate the acute systemic inflammatory response to welding fume
      exposure. METHODS: Twenty four welders (42% smokers) and 13 non-exposed controls
      (23% smokers) were monitored at a welding school. Exposure to fine particulate
      matter (PM2.5) was assessed using cyclone samplers. Markers of systemic
      inflammation, including C-reactive protein (CRP), fibrinogen, and white blood
      cell (WBC) levels, were determined in peripheral blood samples collected at
      baseline and after 5.3 (SD 1.0) hours of exposure. RESULTS: The median PM2.5
      concentration for welders was 1.66 mg/m3, which was significantly greater than
      that for controls (0.04 mg/m3). Compared to non-smokers, smokers had a
      significantly higher baseline WBC count, but comparable levels of CRP and
      fibrinogen. In non-smokers, welding fume exposure was associated with a
      significant increase in WBC and neutrophil counts immediately following exposure
      (+0.8x10(3)/mul, 95% CI 0.1 to 1.6, and +1.0x10(3)/mul, 95% CI 0.4 to 1.7,
      respectively). A significant decrease in fibrinogen levels was observed in non
      smokers (-32 mg/dl, 95% CI -63 to -1). No significant changes in WBC, neutrophil,
      and fibrinogen levels were found in smokers. Sixteen hours after welding
      exposure, CRP levels were found to be significantly increased in both non-smokers
      and smokers (0.90 mg/l, 95% CI 0.17 to 1.64). PM2.5 concentrations were found to
      be significantly associated with absolute neutrophil counts in non-smokers, and
      CRP levels in both non-smokers and smokers. CONCLUSIONS: High levels of welding
      fume exposure induce acute systemic inflammation in a relatively young, healthy
      working population. These results also suggest that smoking may modify the effect
      of welding fume exposure on specific inflammatory markers.

PMID- 15723881
TI  - The procoagulant potential of environmental particles (PM10).
AB  - BACKGROUND AND AIMS: Epidemiology studies have shown that cardiovascular (CV)
      disease is primarily responsible for the mortality associated with increased
      pulmonary environmental particle (PM10) exposure. The mechanisms involved in PM10
      mediated CV effects are unknown although changes in plasma viscosity and in the
      homoeostasis of blood coagulation have been implicated. It was hypothesised that
      PM10 exposure would result in an inflammatory response and enhance the activation
      of the extrinsic coagulation mechanisms in pulmonary and vascular cells in
      culture. METHODS: Primary human monocyte derived macrophages and human umbilical
      cord vein endothelial, human alveolar type II epithelial (A549), and human
      bronchial epithelial (16HBE) cells were tested for their inflammatory and
      procoagulant response to PM10 exposure. IL-8, tissue factor (TF), and tissue
      plasminogen activator (tPA) gene expression and protein release, and coagulation
      enhancing ability of culture media were determined 6 and 24 hours following
      exposure. RESULTS: The culture media from macrophages and 16HBE bronchial
      epithelial cells, but not A549 cells, exposed to PM10 had an enhanced ability to
      cause clotting. Furthermore, H2O2 also increased the clotting activity. Apoptosis
      was significantly increased in macrophages exposed to PM10 and LPS as shown by
      annexin V binding. TF gene expression was enhanced in macrophages exposed to
      PM10, and HUVEC tissue factor and tPA gene and protein expression were inhibited.
      CONCLUSIONS: These data indicate that PM10 has the ability to alter macrophage,
      epithelial, and endothelial cell function to favour blood coagulation via
      activation of the extrinsic pathway and inhibition of fibrinolysis pathways.

PMID- 15723882
TI  - Traumatic work related mortality among seafarers employed in British merchant
      shipping, 1976-2002.
AB  - AIMS: To establish the causes and circumstances of all traumatic work related
      deaths among seafarers who were employed in British merchant shipping from 1976
      to 2002, and to assess whether seafaring is still a hazardous occupation as well
      as a high risk occupation for suicide. METHODS: A longitudinal study of
      occupational mortality, based on official mortality files, with a population of
      1,136,427 seafarer-years at risk. RESULTS: Of 835 traumatic work related deaths,
      564 were caused by accidents, 55 by suicide, 17 by homicide, and 14 by drug or
      alcohol poisoning. The circumstances in which the other 185 deaths occurred,
      including 178 seafarers who disappeared at sea or were found drowned, were
      undetermined. The mortality rate for 530 fatal accidents that occurred at the
      workplace from 1976 to 2002, 46.6 per 100,000 seafarer-years, was 27.8 times
      higher than in the general workforce in Great Britain during the same time
      period. The fatal accident rate declined sharply since the 1970s, but the
      relative risk of a fatal accident was 16.0 in 1996-2002. There was no reduction
      in the suicide rate, which was comparable to that in most high risk occupations
      in Britain, from 1976 to 1995; but a decline since 1995. CONCLUSIONS: Although
      there was a large decline in the fatal accident rate in British shipping,
      compared to the general workforce, seafaring has remained a hazardous occupation.
      Further prevention should focus on improvements in safety awareness among
      seafarers and shipping companies, reductions in hazardous working practices, and
      improvements in care for seafarers at risk of suicide.

PMID- 15723883
TI  - Differential effects of lead exposure on components of verbal memory.
AB  - AIMS: To determine if verbal learning and memory requiring acquisition and
      retention of information is differentially affected by lead exposure. METHODS:
      The Rey Auditory Verbal Learning Test (RAVLT), a test of verbal learning and
      memory, was administered to 256 English speaking lead smelter workers who had a
      mean (SD) age of 41 (9.4) years and employment duration of 17 (8.1) years. Lead
      exposure variables, based on up to 25 years of prior blood lead data, included a
      mean (SD) current blood lead (PbB) of 28 (8.8) microg/dl, working lifetime time
      weighted average blood lead (TWA) of 39 (12.3) microg/dl, and working lifetime
      integrated blood lead index (IBL) of 728 (434.4) microg-y/dl. Associations of
      these chronic and recent lead exposure variables with measures from the RAVLT
      were modelled through multiple linear regressions after controlling for age and
      educational achievement. RESULTS: PbB was not associated with any of the RAVLT
      variables. However, TWA and IBL contributed significantly to the explanation of
      variance of measures of encoding/storage and retrieval but not to immediate
      memory span, attention, and learning. Grouping study participants by RAVLT
      performance according to three recognised clinical memory paradigms showed
      significantly higher TWA and IBL in the group with "generalised memory
      impairment" after adjusting for age and educational achievement. We examined
      recall mechanisms in each group by serial position in the word list and found
      stronger primacy (recall of words from the beginning of the list) in the "no
      impairment" and "retrieval difficulties" groups while the "generalised memory
      impairment" group had better performance on recency (recall of words from the end
      of the list). CONCLUSIONS: Lead exposure over years and not PbB interfered with
      the organisation and recall of previously learned verbal material. Chronic lead
      exposure affects encoding/storage and retrieval of verbal information.

PMID- 15723884
TI  - Self-reported workplace related ergonomic conditions as prognostic factors for
      musculoskeletal symptoms: the "BIT" follow up study on office workers.
AB  - AIMS: To identify prognostic ergonomic and work technique factors for
      musculoskeletal symptoms among office workers and in a subgroup with highly
      monotonous repetitive computer work. METHODS: A baseline questionnaire was
      delivered to 5033 office workers in 11 Danish companies in the first months of
      1999, and a follow up questionnaire was mailed in the last months of 2000 to 3361
      respondents. A subgroup with highly monotonous repetitive computer work was
      formed including those that were repeating the same movements and/or tasks for at
      least 75% of the work time. The questionnaire contained questions on ergonomic
      factors and factors related to work technique. The outcome variables were based
      on the frequency of musculoskeletal symptoms during the last 12 months. Logistic
      regression analyses were used to identify prognostic factors for symptoms in the
      three body regions. RESULTS: In total, 39%, 47%, and 51% of the symptomatic
      subjects had a reduced frequency of symptom days in the neck/shoulder, low back,
      or elbow/hand region, respectively. In all regions more men than women had
      reduced symptoms. In the multivariate logistic regression analyses, working no
      more than 75% of the work time with the computer was a prognostic factor for
      musculoskeletal symptoms in the neck/shoulder and elbow/hand, and a high
      influence on the speed of work was a prognostic factor for symptoms in the low
      back. In the subgroup with highly monotonous repetitive computer work, the odds
      ratios of the prognostic factors were similar to those for the whole group of
      office workers. CONCLUSION: When organising computer work it is important to
      allow for physical variation with other work tasks, thereby avoiding working with
      the computer during all the work time, and further to consider the worker's own
      influence on the speed of work.

PMID- 15723885
TI  - Municipal pleural cancer mortality in Spain.
AB  - BACKGROUND: Pleural cancer is a recognised indicator of exposure to asbestos and
      mesothelioma mortality. AIMS: To investigate the distribution of municipal
      mortality due to this tumour, using the autoregressive spatial model proposed by
      Besag, York, and Mollie. METHODS: It was possible to compile and ascertain the
      posterior distribution of relative risk on the basis of a single Bayesian spatial
      model covering all of Spain's 8077 municipal areas. Maps were plotted depicting
      standardised mortality ratios, smoothed relative risk (RR) estimates, and the
      distribution of the posterior probability that RR >1. RESULTS: There was a higher
      risk of death due to pleural cancer in well defined towns and areas, many of
      which correspond to municipalities where asbestos using industries once existed
      for many years, the prime example being the municipal pattern registered for
      Barcelona Province. The quality of mortality data, the suitability of the model
      used, and the usefulness of municipal atlases for environmental surveillance are
      discussed.

PMID- 15723886
TI  - World at work: research and testing laboratories.

PMID- 15723887
TI  - Intervention studies in occupational epidemiology.

PMID- 15723888
TI  - Editorial: new psychological interventions in chronic illness: towards examining
      mechanisms of action and improved targeting.

PMID- 15723889
TI  - Learning from success and failure in psychosocial intervention: an evaluation of
      low birth weight prevention trials.
AB  - The object of the study was to evaluate the research designs of social support
      interventions for prevention of low birth weight (LBW). A literature search of
      published articles identified 12 randomized controlled trials of social support
      to prevent LBW birth. These were evaluated using specific methodological criteria
      for effective intervention research. Only one study showed a significant
      reduction in LBW. However, none of the studies met all of the proposed criteria
      for rigorous intervention research. It is premature to conclude that social
      support interventions are ineffective in preventing LBW. Specific recommendations
      for future intervention research design are outlined.

PMID- 15723890
TI  - Autonomic effects of expressive writing in individuals with elevated blood
      pressure.
AB  - We evaluated systolic and diastolic blood pressure, heart rate variability and
      skin conductance at baseline, and 1 and 4 months in 38 participants with elevated
      blood pressure, randomly assigned to expressive writing or control groups. There
      was a significant interaction such that the very low frequency wave of heart rate
      variability increased over time only in controls, suggesting potentially
      protective buffering in expressive writing. Systolic and diastolic blood pressure
      also decreased significantly from baseline to 1 month in expressive writing.
      Consistent with inhibition, Anger-In moderated effects of writing on 4-month DBP.
      Overall, expressive writing demonstrated short-term autonomic benefits and longer
      term moderated effects.

PMID- 15723891
TI  - The effects of expressive writing on pain, depression and posttraumatic stress
      disorder symptoms in survivors of intimate partner violence.
AB  - This study examined the effects of expressive writing on depression,
      posttraumatic stress disorder (PTSD) and pain symptoms among women who have
      survived intimate partner violence (IPV). Forty-seven women completed baseline
      and four-month follow-up assessments and were randomly assigned to four writing
      sessions of either expressive writing focused on traumatic life events or writing
      about a neutral topic. Main effects were not significant for changes in
      depression, pain or PTSD symptoms. However, among depressed women, those assigned
      to expressive writing showed a significantly greater drop in depression. For
      depressed women with IPV histories, expressive writing may lead to reduced
      depression.

PMID- 15723893
TI  - Effect of a brief cognitive training programme in patients with long-lasting back
      pain evaluated as unfit for surgery.
AB  - The aim of the study was to evaluate the effect of cognitive intervention
      (information and physical exercise), on patients with long-lasting back pain
      referred for surgical evaluation at an orthopaedic hospital, but evaluated as
      unfit for surgery. One hundred and fifty-two patients were randomized to a five
      days intervention or control. The intervention had no significant effects on
      pain. At three-month follow-up, the patients in the intervention group used
      significantly more active strategies to cope with the back pain compared to the
      control group. This effect seemed to increase over time, being more pronounced at
      one-year follow-up evaluation.

PMID- 15723894
TI  - A randomized controlled graded exercise trial for chronic fatigue syndrome:
      outcomes and mechanisms of change.
AB  - The aim of this study was to investigate the potential mechanisms underlying the
      efficacy of graded exercise therapy for chronic fatigue syndrome (CFS). Forty
      nine CFS patients were randomized to a 12-week graded exercise programme or to
      standard medical care. At the end of treatment the exercise group rated
      themselves as significantly more improved and less fatigued than the control
      group. A decrease in symptom focusing rather than an increase in fitness mediated
      the treatment effect. Graded exercise appears to be an effective treatment for
      CFS and it operates in part by reducing the degree to which patients focus on
      their symptoms.

PMID- 15723892
TI  - Decreased depression up to one year following CBSM+ intervention in depressed
      women with AIDS: the smart/EST women's project.
AB  - This prospective multisite Phase III clinical trial (Miami, New York, New Jersey)
      investigated the long-term (one year) effects of a 10-week group cognitive
      behavioral stress management/expressive supportive therapy (CBSM+) intervention
      on disadvantaged minority women living with AIDS. The CBSM+ intervention
      consisted of 10-weekly group session of stress management, cognitive-behavioral
      skill training, relaxation techniques and expressive-supportive therapeutic
      strategies. The primary study outcome was self-reported depression scores as
      measured by the BDI. The CBSM+ Group intervention significantly decreased
      depression scores on the BDI for women following the intervention and maintained
      the decreased level at one-year follow-up.

PMID- 15723895
TI  - Evaluation of the UCL diabetes self-management programme (UCL-DSMP): a randomized
      controlled trial.
AB  - Self-management has been described as the cornerstone of care for diabetes. Many
      self-management studies are limited by poor methodology and poor descriptions of
      the intervention. The current study developed a theoretically based self
      management programme for patients with type 2 diabetes, which was evaluated via a
      randomized controlled trial. At immediate post-intervention and three-month
      follow-up the intervention group showed significant improvement relative to
      controls on self-management behaviours, quality of life and illness beliefs. A
      trend towards improved HbA1c was also observed. Documentation in a manual and
      development of a training programme for facilitators ensures the programme is
      replicable.

PMID- 15723896
TI  - Effects of emotional disclosure on psychological and physiological outcomes in
      patients with rheumatoid arthritis: an exploratory home-based study.
AB  - The effects of an exploratory, home-based emotional disclosure intervention on
      psychological and physiological outcomes were assessed in patients with
      rheumatoid arthritis. Patients were randomly assigned to a disclosure group (n =
      19) in which they wrote/talked about traumatic personal experiences, or to a
      control group (n = 15) in which they wrote/talked about the events of a
      particular day. Participants undertook these tasks for periods of 20 minutes on 4
      consecutive days. The disclosure group demonstrated increases in negative mood
      and objective markers of disease activity at 1 week post-intervention. However,
      there were significant trends for the disclosure group to demonstrate minor
      improvements in mood and stability in disease activity, compared with the control
      group. These group differences appeared to be due to deteriorations in the
      control group more than improvements in the disclosure group.

PMID- 15723897
TI  - Heterosexual behavioral maintenance and change following HIV counseling and
      testing.
AB  - This study investigated heterosexual HIV risk behaviors, changes in stage of
      change for safer sex and factors associated with such changes, among a diverse
      sample of 560 heterosexually active individuals presenting at publicly funded HIV
      C&T sites. Questionnaires were administrated before HIV C&T, and three months
      afterwards. Positive serostatus was the most significant predictor of safer
      behavior after C&T. Many seronegative participants stopped sex with non-main
      partners. Behaviors with main partners were particularly resistant to change.
      Predictors of change varied by stage at pre-test. C&T services should tailor
      approaches and referrals based on stage of change and other client
      characteristics.

PMID- 15723898
TI  - Googly from down under: hearing impairment and early intervention.

PMID- 15723899
TI  - A deficit that needs attention.

PMID- 15723900
TI  - Respiratory support of infants with bronchiolitis related apnoea: is there a role
      for negative pressure?

PMID- 15723901
TI  - The National Patient Safety Agency.

PMID- 15723902
TI  - Good research conduct.

PMID- 15723904
TI  - An open letter to Doctors Mather and Bannon.

PMID- 15723903
TI  - Informing children and parents about research.

PMID- 15723905
TI  - Intra-cardiac Burkitt's lymphoma.

PMID- 15723906
TI  - Hearing impairment: a population study of age at diagnosis, severity, and
      language outcomes at 7-8 years.
AB  - BACKGROUND: Better language outcomes are reported for preschool children with
      hearing impairment (HI) diagnosed very early, irrespective of severity. However,
      population studies of older children are required to substantiate longer term
      benefits of early detection. AIMS: To study impact of age of diagnosis and
      severity of HI in a population cohort of 7-8 year old children. METHODS: Eighty
      eight 7-8 year old children born in Victoria, who were (a) fitted with hearing
      aids for congenital HI by 4.5 years and (b) did not have intellectual or major
      physical disability were studied. Main outcome measures were Clinical Evaluation
      of Language Fundamentals (CELF) and Peabody Picture Vocabulary Test (PPVT).
      Predictors were pure tone average (0.5, 1, 2 kHz) in better ear at diagnosis and
      age at diagnosis. Marginal (adjusted) means were estimated with general linear
      models. RESULTS: Response rate was 67% (n = 89; 53 boys). Mean age at diagnosis
      was 21.6 months (SD 14.4); 21% had mild, 34% moderate, 21% severe, and 24%
      profound HI; mean non-verbal IQ was 104.6 (SD 16.7). Mean total CELF score was
      76.7 (SD 21.4) and mean PPVT score 78.1 (SD 18.1). Age of diagnosis, adjusted for
      severity and IQ, did not contribute to language scores. In contrast, adjusted
      mean CELF and PPVT language scores fell sequentially with increasing severity of
      HI. CONCLUSIONS: More severe HI, but not later diagnosis, was strongly related to
      poorer language outcomes at 7-8 years. Further systematic study is needed to
      understand why children with hearing impairment have good or poor outcomes.

PMID- 15723907
TI  - The association between hyperkinesis and breakdown of parenting in clinic
      populations.
AB  - BACKGROUND: There is increasing recognition that child based, as well as parent
      based factors may be associated with children being excluded from their families.
      Despite the distress routinely observed among the parents of hyperactive
      children, there is little research on this in clinic populations. AIMS: To
      examine removals from home in a typical secondary care population, where
      hyperkinesis was accurately diagnosed. METHODS: A total of 201 cases were coded
      using mulitaxial ICD-10 criteria and Jarman indices derived from census data.
      RESULTS: Hyperkinetic children were more than three times more likely to have
      suffered removal from home than children with other psychiatric diagnoses,
      independent of any psychosocial measure. CONCLUSION: Hyperkinesis is a specific
      risk factor for removal from home, which can operate in the absence of other
      psychosocial stressors. Screening children for hyperactivity is now simple, and
      the routine paediatric examination for children accommodated by the local
      authority gives an opportunity for early detection and treatment of hyperactivity
      in children at risk of family breakdown.

PMID- 15723908
TI  - Weight and energy: parents' and children's perspectives on managing cystic
      fibrosis diet.
AB  - AIMS: To explore the meanings that parents and children attach to food and
      eating, and how these influence their approaches to dietary management of cystic
      fibrosis (CF). METHODS: Ethnographic design using in-depth interviews with 32
      children with CF (aged 6-14 years) and their parents, and participant
      observations during visits to CF clinics with a sub-group of 21 children. Data
      were analysed using the constant comparative method and theoretical sampling was
      used to further explore and develop emergent themes. RESULTS: Dietary management
      was found to be a demanding task for children and their parents, and priorities
      differed between them. A priority of feeding for parents was to protect their
      children's long term physical health and survival by keeping their weight up. A
      challenge for parents was to ensure their children's cooperation with eating. A
      priority for children in being healthy was to have energy for physical activities
      and so energy rather than weight was of immediate relevance to their daily lives.
      These differences between parents and children gave rise to tensions and
      conflicts in their interactions with one another in managing diet. CONCLUSIONS:
      Healthcare professionals should take account of the meanings that children and
      their parents attach to food and eating that can influence their decisions about
      implementing CF dietary recommendations. The role of children in making food
      choices has implications for acknowledging them as active participants in their
      dietary care and for adopting child centred approaches to dietary advice for CF.

PMID- 15723909
TI  - Deprivation, smoking, and quality of life in asthma.
AB  - AIMS: To explore associations of deprivation and smoking, with prevalence of
      asthma, wheeze, and quality of life. METHODS: Survey, using International Study
      of Asthma and Allergies in Childhood (ISAAC) methodology, of children aged 13-14
      years attending Scottish schools previously surveyed in 1995. RESULTS: 4665/5247
      (89%) pupils completed questionnaires. 3656/4665 (78.4%) had missed school for
      any reason in the last 12 months, 587 (12.6%) because of asthma or wheeze.
      Compared to children with 1-3 wheeze attacks per year, those with >12 attacks in
      the last year were more likely to have missed school, twice as likely to have
      missed physical education in the last month, to report interference with home
      activities, or to have visited accident and emergency departments, and three
      times more likely to have been hospitalised. Deprivation was not independently
      associated with self-reported asthma or wheeze, but was associated with school
      absence, either for any reason or specifically for asthma or wheeze, but not with
      use of services such as accident and emergency visits, doctor visits, or hospital
      admissions. Active smoking was associated with wheezy symptoms, and active and
      passive smoking with use of medical services. These associations were independent
      of wheeze severity, treatment taken, and other associated atopic conditions.
      Smoking also had an impact on school absence and home and school activities.
      CONCLUSIONS: Deprivation does not affect the prevalence of asthma or wheeze.
      Exposure to cigarette smoke was associated with the increased use of services.
      Deprivation and smoking have independent adverse effects on the quality of life
      in subjects with asthma or wheeze.

PMID- 15723910
TI  - Precocious pubarche is associated with SGA, prematurity, weight gain, and
      obesity.
AB  - BACKGROUND: Perinatal stress is thought to underlie the Barker sequelae of low
      birth weight, of which precocious pubarche may be a manifestation. AIMS: To
      explore whether prematurity as well as smallness for gestational age (SGA)
      predisposes to precocious pubarche, and the potential role of excess weight gain
      during childhood. METHODS: Retrospective chart review of 89 children (79 girls)
      with precocious pubarche. RESULTS: Sixty five per cent were overweight/obese at
      diagnosis, compared with 19-24% of Australian children. Thirty five per cent had
      a history of SGA and 24% of prematurity. Weight SDS increased from birth to
      diagnosis in 91% of children. The mean change in weight SDS from birth to
      diagnosis was greater in those who were SGA (2.8, 95% CI 2.2 to 3.4) versus AGA
      (1.7, 95% CI 1.3 to 2.2), with no difference in the incidence of
      overweight/obesity. The latter was lower among children born premature (40%
      versus 72% term) but was associated with a mean increase in weight of 1.3 SDS
      during childhood. Nine out of ten girls and boys with precocious pubarche had at
      least one of the three risk factors studied. CONCLUSIONS: Both prematurity and
      SGA were associated with precocious pubarche, as was overweight/obesity,
      irrespective of size or gestation at birth. Excess weight gain in childhood may
      predispose to precocious pubarche in susceptible individuals.

PMID- 15723911
TI  - Causes of lead toxicity in a Nigerian city.
AB  - BACKGROUND: Up to 70% of young Nigerian children have been reported to have blood
      lead concentrations > or =10 microg/dl. AIMS: To better elucidate risk factors
      for lead toxicity among Nigerian families with children at risk for lead
      toxicity. METHODS: Two geographic wards in Jos, Nigeria were selected for study,
      one previously reported to have a high mean blood lead level (37 (SD 13)
      microg/dl) and one with a lower mean blood lead level (17 (SD 10) microg/dl) in
      young children. Data pertaining to potential risk factors for lead exposure were
      collected from children and adults in 34 households. RESULTS: The mean (SD) blood
      lead concentration of 275 subjects, aged 3 weeks to 90 years, was 8.7 (5.7)
      microg/dl (range 1-34 microg/dl); 92 (34%) had concentrations > or =10 microg/dl.
      In multivariate analysis, an age of 5 years and under, flaking house paint,
      residence near a gasoline seller, male gender, increasing maternal and paternal
      education, and use of a lead ore eye cosmetic were independently associated with
      greater blood lead concentration. Vehicle ownership was associated with reduced
      lead concentration. Compared with the low-lead ward, residence in the high-lead
      ward remained significantly associated with greater lead values, indicating that
      additional factors likely contribute to lead exposure. CONCLUSION: Although the
      cause of increased lead levels in Jos appears to be multi-factorial, several
      remediable sources contribute to lead exposure in Nigeria.

PMID- 15723912
TI  - Trends in age at diagnosis of Turner syndrome.
AB  - The age at diagnosis of 242 girls with Turner syndrome (TS) treated in Belgium
      with growth hormone between 1991 and 2002 was evaluated. The median (range) age
      at diagnosis was 6.6 (0-18.3) years. Patients with 45,X karyotype were diagnosed
      earlier than patients with other karyotypes. Compared to a previous survey,
      performed on 100 patients 12 years earlier, more patients were diagnosed during
      infancy and childhood, and less during adolescence. However, in 22% of the girls
      the diagnosis was made after the age of 12 years; these girls showed the largest
      height deficit. As early diagnosis has several potential advantages we recommend
      that a cytogenetic analysis should be considered in all girls with unexplained
      short stature with height below -2 SD of the mean for age or below the parent
      specific lower limit of height.

PMID- 15723913
TI  - A comparison of pain scales in Thai children.
AB  - Three commonly used pain scales, the visual analogue scale, the Wong-Baker Faces
      Pain Scale, and the Faces Pain Scale Revised were administered to 122 Thai
      children, of whom half were HIV infected, in order to assess their validity.
      These scales presented moderate to good correlation and moderate agreement,
      sufficient for valid use in Thai children.

PMID- 15723914
TI  - Evidence for autism in folklore?

PMID- 15723915
TI  - Infant growth and income 50 years later.
AB  - Among 4630 boys, irrespective of the social class into which they were born,
      those who grew slowly during infancy had poor educational achievements and had
      lower incomes than those who grew more rapidly. One interpretation of this is
      that biological processes linked to slow infant growth may lead to lifelong
      impairment of cognitive function.

PMID- 15723916
TI  - Questionnaire survey of British Society for Paediatric Gastroenterology
      Hepatology And Nutrition (BSPGHAN) members to examine workload and resources for
      paediatric gastroenterologists.

PMID- 15723917
TI  - Problem based learning in a junior doctor teaching programme.
AB  - BACKGROUND: Problem based learning (PBL) is used increasingly in undergraduate
      medical education, but there are few postgraduate medical studies. AIM: To
      compare SHO learning outcomes for a PBL course with a traditional didactic
      course. METHODS: As part of their protected teaching programme, 14 senior house
      officers (SHOs) were taught about paediatric dermatology using a traditional
      didactic course. Six months later, the new SHOs received a PBL course including
      small group teaching and a study guide. Both the traditional and the PBL group
      were assessed using multiple choice questions (MCQs), an objective structured
      clinical examination (OSCE), and pre- and post-course self-assessment sheets.
      SHOs completed course evaluation sheets. RESULTS: There was no significant
      difference in learning outcome between the traditional and PBL courses as
      assessed by the MCQs, OSCE, and self-assessment sheets. The PBL course was well
      appreciated by SHOs who liked variety in the teaching programme. CONCLUSIONS: The
      PBL and traditional course had equivalent learning outcomes. PBL adds variety to
      junior doctor protected teaching programmes and can be a useful tool for doctors
      working shift patterns.

PMID- 15723919
TI  - Exploring diagnostic processes: social science perspectives.
AB  - This review explores social science analyses of diagnosis of childhood
      neurological disabilities. The paper moves through three sections, which capture
      the historical and conceptual trends within the literature. The first focuses on
      work identifying the need to communicate effectively with parents when giving a
      diagnosis, the second explores the role parents can play as "partners" or
      contributors to diagnosis, and the final section goes further in exploring the
      social complexity of diagnoses in order to examine the embedded nature of social
      practices, power relations and hierarchies, and institutions in the diagnosis
      encounter.

PMID- 15723918
TI  - The role of distance learning in specialist medical training.
AB  - The Quality Assurance Agency for Higher Education (QAA) defines distance learning
      (DL) as "a way of providing higher education that involves the transfer to the
      student's location of the materials that form the main basis of study, rather
      than the student moving to the location of the resource provider".

PMID- 15723920
TI  - Review of treatment of bronchiolitis related apnoea in two centres.
AB  - AIMS: To determine whether the use of negative pressure ventilation (NPV) was
      associated with a lower rate of endotracheal intubation in infants with recurrent
      apnoea secondary to acute bronchiolitis. METHODS: Retrospective review of two
      paediatric intensive care units (PICU) databases and case notes; one PICU offered
      NPV. RESULTS: Fifty two infants with bronchiolitis related apnoea were admitted
      to the two PICUs (31 to the NPV centre). There were no significant differences
      between infants in the two centres in age and weight on admission, gestational
      age at birth, birth weight, history of apnoea of prematurity or chronic lung
      disease, days ill before referral, respiratory syncytial virus status, oxygen
      requirement before support, and numbers retrieved from secondary care centres.
      Respiratory support was provided to all 31 infants in the NPV centre (23 NPV, 8
      PPV), and 19/21 in the non-NPV centre (18 PPV, 1 CPAP); the NPV centre had lower
      rates of endotracheal intubation rates (8/31 v 18/21), shorter durations of stay
      (median 2 v 7 days), and less use of sedation (16/31 v 18/21). In the two years
      after the NPV centre discontinued use of NPV, 14/17 (82%) referred cases were
      intubated, with a median PICU stay of 7.5 days. CONCLUSIONS: The use of NPV was
      associated with a reduced rate of endotracheal intubation, and shorter PICU stay.
      A prospective randomised controlled trial of the use of NPV in the treatment of
      bronchiolitis related apnoea is warranted.

PMID- 15723921
TI  - No evidence of an association between MMR vaccine and gait disturbance.
AB  - BACKGROUND: MMR vaccine has been reported to cause gait disturbance, and this
      possible association has been claimed to support the MMR-causes-autism theory.
      AIMS: To determine whether any association between gait disturbance and MMR
      vaccination exceeds the age related background rate of gait disturbance, using
      record linkage and self control case series analyses. METHODS: MMR vaccination
      records were linked to hospital admission and general practitioner attendance
      data. An increased rate of gait problems with onset in various intervals in the
      60 day period after MMR vaccination was looked for in children aged 12 to <24
      months. RESULTS: No evidence of an increased rate of hospital admission or
      general practice consultations for gait disturbance was found in the putative
      post-vaccination risk periods. CONCLUSIONS: This study provides no evidence for a
      causal association between MMR and gait disturbance.

PMID- 15723922
TI  - Epidemiology of apparent life threatening events.
AB  - AIMS: To investigate the epidemiology and risk factors of apparent life
      threatening events (ALTE). METHODS: A prospective study enrolled all live-born
      infants in the Tyrol (1993-2001). Information on pregnancy, sociodemographic
      characteristics, child care practices, and infant's behaviour in the first four
      to six weeks of life was collected with a standardised questionnaire, and was
      available for 44,184 infants. ALTE was identified from hospital admission
      records. RESULTS: During the study period 164 ALTE cases were identified,
      corresponding to an incidence of 2.46/1000 live births. In 73 of these infants no
      cause for the event and no comorbidity could be found (idiopathic ALTE). On
      average ALTE manifested ten weeks earlier than SIDS. Of various SIDS risk factors
      in the survey area, the prone sleeping position, smoking during pregnancy, low
      gestational age, profuse night sweating, and family history of infant death
      showed a moderate relation to the risk of overall ALTE, but only smoking
      maintained significance in the multivariate risk model. None of these variables
      was associated with idiopathic ALTE. In contrast to SIDS the frequency of ALTE
      did not change during the study period. None of the ALTE infants experienced SIDS
      later in life. Behavioural abnormalities such as feeding difficulties, episodes
      of pallor, cyanotic episodes, and repeated apnoea episodes were strongly
      associated with an increased risk of overall and idiopathic ALTE. CONCLUSIONS:
      Although there are some similarities in the clinical presentation and
      epidemiology of SIDS and ALTE, differences clearly predominate. Accordingly, ALTE
      and SIDS should not be considered different manifestations of the same disease
      process.

PMID- 15723923
TI  - Feasibility of neuropsychological assessment in leukaemia patients shortly after
      diagnosis: directions for future prospective research.
AB  - AIMS: To study neuropsychological functioning of newly diagnosed children with
      acute lymphoblastic leukaemia (ALL) within two weeks after diagnosis in order to
      determine the feasibility of a sibling controlled prospective study design.
      METHODS: Fifty consecutive patients (median age at testing 6.6 years, range 4-12)
      were included in a prospective, longitudinal, nationwide study. Treatment would
      include intrathecal and systemic chemotherapy according to the DCLSG ALL-9
      protocol. Children were evaluated with an extensive neuropsychological battery
      including measures of intelligence, memory, attention, language, visual
      constructive function, and fine-motor abilities within two weeks after start of
      the chemotherapy. The control group consisted of 29 healthy siblings (median age
      at testing 8.2 years, range 4-12), who were tested <4 weeks after the patients'
      assessment. RESULTS: Mean scores on Wechsler Intelligence Scales did not differ
      significantly between patients and siblings; mean IQ scores for both the patients
      and the controls were high average. To examine specific neuropsychological
      functions, norm scores based on the exact age were acquired by fitting
      procedures, but no significant differences were found. CONCLUSIONS:
      Neuropsychological assessment of patients during early hospitalisation is
      feasible. The results indicate no adverse effect of illness and psychological
      factors on IQ and neuropsychological functioning of patients with recently
      diagnosed ALL. The prospective design of this study of cognitive late effects of
      chemotherapy will allow discrimination between adverse sequelae of disease and
      treatment.

PMID- 15723924
TI  - Adenovirus associated haematuria.
AB  - Adenovirus is a common respiratory virus in children and is known to cause acute
      haemorrhagic cystitis, particularly in the immunosuppressed. In immunocompetent
      children with adenoviral infection the incidence of haematuria was 18.6%, with
      2.4% of these children having macroscopic haematuria and upper tract involvement.

PMID- 15723925
TI  - Aetiological investigation of sensorineural hearing loss in children.
AB  - A survey of aetiological investigations arranged on children with severe/profound
      bilateral sensorineural hearing impairment by ENT consultants and community
      paediatricians working in audiology is described. Greater routine use of ECG,
      urine analysis, and ophthalmological assessment is needed, with a more selective
      approach to other investigations as recommended by the British Association of
      Audiological Physicians (BAAP) and the British Association of Community Doctors
      in Audiology (BACDA).

PMID- 15723926
TI  - Automatic external defibrillation in a 6 year old.
AB  - A case is reported in which an automatic external defibrillator (AED) was used
      during the successful resuscitation of a 6 year old child in out-of-hospital
      cardiac arrest, despite the fact that these devices are not recommended in
      children under 8 years. The interpretation of resuscitation protocols is
      discussed and new developments in this area reported.

PMID- 15723927
TI  - Epidemiology of low back pain in children and adolescents.
AB  - It has been estimated that over 80% of the population will report low back pain
      (LBP) at some point in life, and each year 7% of the adult population consult
      their GP with symptoms. Prevalence increases with age, reaching a peak during the
      sixth decade of life. Until recently little was known about LBP at young ages.
      Clinically it was perceived to be uncommon-with few children consulting because
      of LBP in primary care. Large prospective epidemiological studies have shown
      that, in those free of LBP at baseline, the best predictor of future onset is a
      previous history of LBP. Therefore, to understand the epidemiology of LBP, and
      what predisposes someone to a trajectory of LBP in adult life, it is important to
      examine the condition at young ages, to determine factors responsible for onset
      of initial episodes, and to examine whether LBP in childhood is related to
      symptoms in adulthood.

PMID- 15723928
TI  - Acute haemorrhagic oedema of infancy.

PMID- 15723931
TI  - Is nasogastric fluid therapy a safe alternative to the intravenous route in
      infants with bronchiolitis?

PMID- 15723929
TI  - State of the world's children: life beyond survival.

PMID- 15723932
TI  - Are methylxanthines effective in preventing or reducing apnoeic spells in infants
      with bronchiolitis?

PMID- 15723934
TI  - "Never mind, when is dinner ready?" Living with Prader-Willi syndrome.

PMID- 15723933
TI  - Are newer macrolides effective in eradicating carriage of pertussis?

PMID- 15723936
TI  - First do no harm...

PMID- 15723935
TI  - Is fragmentation of schedules hampering the uptake of hepatitis B vaccine?

PMID- 15723937
TI  - Hib IgG persistence following early booster dose.

PMID- 15723938
TI  - Correlation between otorhinolaryngologic evaluation and severity of obstructive
      sleep apnea syndrome in snorers.
AB  - OBJECTIVES: To examine whether medical history and nasopharyngeal examination are
      useful for predicting obstructive sleep apnea syndrome (OSAS) and to compare
      these findings with those of the gold standard, polysomnography. DESIGN: Patients
      underwent polysomnography recordings for 2 nights and an otorhinolaryngologic
      examination, including flexible endoscopy and the Muller maneuver. Nasal and
      pharyngeal findings were scored in a semiquantitative way. The medical history of
      each patient was taken using a standardized questionnaire. Anatomic and
      functional findings and patient history were correlated with the mean apnea
      hypopnea index (AHI). SETTING: An otorhinolaryngologic clinic. PATIENTS: A total
      of 101 patients presenting with a primary complaint of snoring. MAIN OUTCOME
      MEASURES: Differences between patients with OSAS and primary snorers were
      assessed using the Mann-Whitney test (anatomic findings), t test (Muller
      maneuver), and chi(2) test after Pearson correlation (questionnaire). P values
      less than .05 were considered statistically significant. RESULTS: The mean +/- SD
      AHI of the patients was 19.7 +/- 21.5); 52 patients had an AHI higher than 10,
      which confirmed the diagnosis of OSAS. These patients tended to report the
      occurrence of apneas more frequently than patients with an AHI of 10 or lower.
      The average ranks (Mann-Whitney findings) of patients with AHIs higher than 10 vs
      those with AHIs of 10 or lower were 52 vs 50 for septal deviation; 50 vs 52 for
      tonsil size; 53 vs 49 for low velum level; and 56 vs 46 for hyperplasia of the
      tongue base. None of these differences reached statistical significance. Mean +/-
      SD narrowing of the airway during the Muller maneuver was significantly (P<.05)
      more pronounced in patients with an AHI higher than 10 than in patients with an
      AHI of 10 or lower at the levels of the velum (80% +/- 20% vs 68% +/- 30%) and
      the tongue base (57% +/- 24% vs 44% +/- 27%). CONCLUSIONS: None of the reported
      medical history and/or anatomic parameters alone or in combination could be used
      to distinguish patients with OSAS from snoring patients. Snoring patients,
      therefore, should be examined at least by a nocturnal screening test for OSAS
      before any therapeutic decision is made.

PMID- 15723939
TI  - Clinical trial of photodynamic therapy with meso-tetra (hydroxyphenyl) chlorin
      for respiratory papillomatosis.
AB  - OBJECTIVE: To determine the efficacy of photodynamic therapy (PDT) with meso
      tetra (hydroxyphenyl) chlorin (m-THPC) photosensitizer for recurrent respiratory
      papillomatosis. DESIGN: Parallel-arm, randomized trial of patients requiring
      surgery at least 3 times yearly with single PDT 6 or 18 months after enrollment
      and 12-month follow-up. Disease extent was scored and papillomas were removed
      during direct endoscopy every 3 months after enrollment. SETTING: Tertiary
      medical centers. PATIENTS: Of 23 patients aged 4 to 60 years enrolled in the
      study, 15 patients, plus 2 in the late group without PDT owing to airway risk,
      completed the study. Six patients withdrew voluntarily after PDT. INTERVENTION:
      Intravenous administration of m-THPC 6 days before direct endoscopic PDT with 80
      to 100 J of light for adults and 60 to 80 J for children. MAIN OUTCOME MEASURES:
      Difference in severity scores between the early and late groups and between pre-
      and post-PDT scores for all patients. Secondary measures were the associations
      between baseline characteristics and response and changes in immune response and
      the prevalence of latent viral DNA. RESULTS: There were significant differences
      between groups, with marked improvement in laryngeal disease across time after
      PDT (P = .006). Five of 15 patients were in remission 12 to 15 months after
      treatment, but there was recurrence of disease after 3 to 5 years. Tracheal
      disease was not responsive to PDT. No change occurred in the prevalence of latent
      human papillomavirus DNA. The immune response to virus improved with clinical
      response. CONCLUSIONS: Use of m-THPC PDT reduces the severity of laryngeal
      papillomas, possibly through an improved immune response. Failure to maintain
      remission with time suggests that this is not an optimal treatment.

PMID- 15723940
TI  - Distorted odorant perception: analysis of a series of 56 patients with parosmia.
AB  - OBJECTIVE: To characterize the self-reported olfactory and gustatory symptoms,
      olfactory function, and causes in parosmia. DESIGN: Assessment of olfactory
      symptoms and function in patients with a chief complaint of parosmia. SETTING: A
      university hospital clinic and research facility. PATIENTS: Fifty-six consecutive
      patients presented to the ORL Clinic, European Hospital Georges Pompidou, with a
      chief complaint of parosmia between October 2001 and November 2003. MAIN OUTCOME
      MEASURES: Subjective olfactory symptom analysis and olfactory function test
      results. RESULTS: The mean duration of parosmia was 63.0 months. Forty patients
      (71.4%) reported associated hyposmia and 16 (28.6%) reported anosmia. Olfactory
      testing revealed moderate to severe olfactory loss in all patients. Quantitative
      and qualitative alterations occurred simultaneously in 32 patients (57.1%);
      parosmia onset occurred within 3 months after quantitative dysosmia in 19
      patients (33.9%) and after 3 months in 5 patients (8.9%). The sensation of
      parosmia was always unpleasant. The main odorant triggers eliciting parosmia are
      described. The mean severity of flavor dysfunction of the population, evaluated
      using a 10-cm visual analog scale, was 6.4. Thirty-one patients (55.4%) viewed
      their olfactory alteration as severely affecting their quality of life. The main
      clinical association of parosmia was upper respiratory tract infection, found in
      42.8% of the patients. Others clinical associations are described. CONCLUSION:
      The series of patients with parosmia presented herein, the largest in the
      literature, permits a clinical description of this rare olfactory abnormality.

PMID- 15723941
TI  - Intratympanic dexamethasone injections as a treatment for severe, disabling
      tinnitus: does it work?
AB  - OBJECTIVE: To test the effectiveness of intratympanic dexamethasone injections as
      a treatment for severe disabling cochlear tinnitus. DESIGN: Randomized,
      prospective, single-blind study. SETTING: Academic tertiary referral hospital.
      PATIENTS: Thirty-six patients with severe disabling tinnitus predominantly of
      cochlear origin were randomly assigned to receive intratympanic injections of a
      dexamethasone solution or isotonic sodium chloride (saline) solution.
      INTERVENTIONS: Under topical anesthesia and after randomization, 36 patients
      received 0.5-mL intratympanic injections once per week for 4 weeks of either a 4
      mg/mL dexamethasone solution or saline solution. Five patients were excluded from
      analysis because they did not complete the treatment or did not return for follow
      up. MAIN OUTCOME MEASURE: Improvement of tinnitus measured with a visual analog
      scale. RESULTS: The 2 groups were similar in age, sex, tinnitus laterality,
      measurement of tinnitus intensity on the visual analog scale, and main otologic
      diagnosis. We considered a 2-point improvement on the visual analog scale to be
      significant. Twenty-nine percent of the ears in the saline group and 33% of the
      ears in the dexamethasone group showed significant improvement immediately after
      completion of treatment. These measurements were not significantly different from
      each other. Follow-up varied from 13 to 31 months, and the patients with improved
      tinnitus returned to the initial measurements over time. CONCLUSIONS: There was
      no advantage in intratympanic injections of dexamethasone over saline solution in
      the treatment of severe, disabling tinnitus. Both solutions produced a
      placebolike improvement.

PMID- 15723942
TI  - Eustachian tube function before recurrence of otitis media with effusion.
AB  - OBJECTIVE: To study the role of eustachian tube function in the development of
      recurrent otitis media with effusion (OME) in children treated with tympanostomy
      tubes for OME. DESIGN: Prospective cohort study. SETTING: Three academic and
      general hospitals. PATIENTS: Children aged 2 to 7 years with a first clinical
      episode of OME that persisted for at least 3 months; 136 (81%) of 168 eligible
      children participated. All children received tympanostomy tubes for bilateral OME
      at study entry. MAIN OUTCOME MEASURE: Recurrence of OME within 6 months of tube
      extrusion. RESULTS: No statistically significant differences were present in
      eustachian tube function test results between ears that developed recurrent OME
      and those that did not. The difference in passive ventilatory function between
      ears with and without OME recurrence was 10 daPa (95% confidence interval, -24 to
      43 daPa) for opening pressure and -3 daPa (95% confidence interval, -18 to 11
      daPa) for closing pressure. The overall difference in the proportion of ears with
      and without OME recurrence that could not equilibrate positive and negative
      applied pressures was 12% (95% confidence interval, -2% to 26%). The proportions
      of ears with and without OME recurrence that induced negative pressure in the
      middle ear by forcefully sniffing were 22% and 31%, respectively (P = .75).
      CONCLUSION: Measurement of ventilatory and protective eustachian tube function
      using the forced response test, the pressure equilibration test, and the sniff
      test has no value in predicting whether children have an increased risk of OME
      recurrence.

PMID- 15723943
TI  - Split-thickness skin graft attachment to bone lacking periosteum.
AB  - OBJECTIVES: To develop an animal model to investigate the survival of split
      thickness skin grafts (STSGs) on bone without periosteum, to compare STSG
      attachment to bone with and without periosteum, and to determine the effect of
      fibrin glue on STSG attachment to bone. DESIGN: Prospective laboratory study.
      SETTING: University laboratory. SUBJECTS: Sprague-Dawley rats. MAIN OUTCOME
      MEASURE: Percentage of survival of the STSGs at 2 weeks determined independently
      by the authors and a third, blinded head and neck surgeon. RESULTS: In experiment
      1, which included 40 rats, the sutured STSGs showed an average survival rate of
      38% when attached to bone with periosteum, 6% when attached to bare bone, and 10%
      when attached to bare bone using fibrin glue. The poor survival rate was thought
      to be attributable to the animals scratching at their bolster dressings. In
      experiment 2, 18 animals underwent a posteriorly based U-shaped flap of skin and
      subcutaneous tissue. The grafts were placed and isolated from the overlying flap
      with a biosynthetic wound dressing. The sutured STSG survival rates were as
      follows: 87% when attached to bone with periosteum, 94% when attached to bare
      bone, and 74% when attached to bare bone using fibrin glue. CONCLUSIONS: The
      survival of STSGs attached to bare bone was comparable to that of STSGs attached
      to bone with periosteum when grafts were protected with the skin-subcutaneous
      flap. The STSGs that were fixed with 0.1 cc of fibrin glue demonstrated poorer
      survival rates than those attached with sutures and were associated with more
      seromas.

PMID- 15723944
TI  - Midfacial reconstruction using calvarial split bone grafts.
AB  - OBJECTIVE: To evaluate the success rate of free calvarial grafts for midfacial
      reconstruction, the relevance of soft tissue coverage, and the influence of
      radiotherapy. DESIGN: Retrospective analysis. SETTING: University medical center.
      PATIENTS: Fifty-six patients (27 tumor cases, 24 trauma cases, and 5 others)
      underwent bony midface reconstruction using calvarial grafts in the past 11
      years. Half of the patients with tumor were additionally treated with radiation.
      INTERVENTIONS: A total of 95 bone transplants were used for reconstruction of the
      zygoma, orbit, and nasal bone. Graft survival and complications were evaluated.
      Grafts with total and partial soft tissue coverage were compared. The influence
      of radiotherapy in the tumor patient group was determined. RESULTS: Graft
      survival was 95.8%. One nasal dorsum graft was totally resorbed. Infection
      occurred in 9 cases, leading to only 1 total and 2 partial graft losses. The
      incidence of dysfunction of the eye due to globe malposition after reconstruction
      of the orbital walls was low. A correlation between radiation and transplant loss
      as well as between soft tissue coverage and graft survival could not be found.
      CONCLUSIONS: For midfacial reconstruction, it is not necessary to fully cover
      calvarial bone grafts by the surrounding soft tissue. Even in patients who will
      undergo postoperative irradiation, calvarial bone grafts are a reliable
      alternative in selected cases.

PMID- 15723945
TI  - Arterial and venous parathyroid hormone levels in minimally invasive surgery.
AB  - OBJECTIVE: To establish if venous and arterial parathyroid hormone (PTH) levels
      are similar during minimal access parathyroid surgery. DESIGN: Prospective study.
      SETTING: Marshfield Clinic, a large multispecialty tertiary care referral center
      in central Wisconsin. PATIENTS: All patients who underwent minimally invasive
      parathyroid surgery over a 10-month period. RESULTS: Fifteen consecutive patients
      were evaluated. There were 11 women and 4 men, with an average age of 65 years.
      All patients underwent a preoperative technetium Tc 99m sestamibi scan, with 11
      localizing to the site of a probable adenoma. Mean ionized calcium levels were
      5.95 mg/dL (1.49 mmol/L) preoperatively and 4.84 mg/dL (1.21 mmol/L)
      postoperatively. Of 13 patients undergoing both arterial and venous sampling,
      mean baseline venous PTH level was 221 pg/mL and 37 pg/mL at 10 minutes after
      excision of suspected adenoma (83% decline). Mean baseline arterial PTH level was
      247 pg/mL and 38 pg/mL at 10 minutes after excision (84% decline). Using the
      Wilcoxon signed rank test, there was no significant difference in the arterial vs
      venous levels at baseline (P = .70) or 10 minutes (P = .48). CONCLUSIONS:
      Intraoperative PTH levels during minimal access parathyroid surgery are similar
      for venous and arterial samples. Blood samples for PTH level monitoring can be
      obtained using a temporary indwelling arterial line.

PMID- 15723946
TI  - Submandibular gland transfer for prevention of xerostomia after radiation
      therapy: swallowing outcomes.
AB  - OBJECTIVE: To assess swallowing outcomes in patients with oropharyngeal carcinoma
      in relation to the Seikaly-Jha procedure for submandibular gland transfer (SJP).
      The SJP has recently been described as beneficial in the prevention of xerostomia
      induced by radiation therapy in patients with head and neck cancer. DESIGN:
      Inception cohort. SETTING: University-affiliated primary care center. PATIENTS: A
      phase 2 clinical trial was conducted from February 1, 1999, through February 28,
      2002, to evaluate SJP in patients with head and neck cancer. During that period,
      a consecutive sample of 51 patients who underwent surgical resection and
      reconstruction with a radial forearm free flap for oropharyngeal carcinoma were
      referred for functional assessment of swallowing after completion of adjuvant
      radiation therapy. At 6 months after surgery, swallowing assessments for 24
      patients were available. INTERVENTION: The cohort of 24 patients included 13 who
      had preservation of 1 submandibular gland (SJP group) and 11 who did not (control
      group). MAIN OUTCOME MEASURES: Quantitative and qualitative aspects of swallowing
      were obtained to determine whether patients in the SJP group performed more
      optimally than those in the control group. RESULTS: Baseline and stimulated
      salivary flow rates were significantly different between groups. Patients in the
      SJP group were able to move the bolus through the oral cavity and into the
      pharynx faster than those in the control group. In addition, patients in the SJP
      group swallowed less often per bolus than patients in the control group. The
      complete swallowing sequence was twice as long in controls. CONCLUSIONS: The SJP
      for submandibular gland transfer appears to be beneficial in promoting more time
      efficient swallowing behaviors. This efficiency has implications for the overall
      well-being and nutritional status of patients with head and neck cancer.

PMID- 15723947
TI  - Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association
      with epidermal growth factor receptor expression.
AB  - OBJECTIVES: To examine the association between cyclooxygenase-2 (COX-2)
      expression with epidermal growth factor receptor (EGFR), vascular endothelial
      growth factor (VEGF), inducible nitric oxide synthase (iNOS), and latent membrane
      protein 1 (LMP-1) expression and with COX-2 promoter methylation status in
      primary nasopharyngeal cancer (NPC) tumors and to determine COX-2 promoter
      methylation status in NPC cell lines. DESIGN: Retrospective study. SETTING:
      Patients with NPC were referred to the Department of Otolaryngology-Head and Neck
      Surgery for treatment. PATIENTS: Formalin-fixed, paraffin-embedded NPC specimens
      from 42 patients were obtained. INTERVENTIONS: Immunohistochemical expression of
      COX-2, EGFR, VEGF, iNOS, and LMP-1 was performed in 42 NPC samples. COX-2
      promoter methylation status was studied in 20 separate specimens and in 4 NPC
      cell lines. MAIN OUTCOME MEASURES: (1) COX-2, EGFR, VEGF, iNOS, and LMP-1
      expression; and (2) COX-2 promotor methylation status. RESULTS: COX-2 was
      overexpressed in 79% of NPC specimens and was associated with EGFR status (P =
      .03) but not with LMP-1 or iNOS. In primary NPC tissue, methylation of the COX-2
      promoter was seen in 4 of 7 COX-2-negative and 1 of 13 COX-2-positive
      immunohistochemical cases. COX-2 promoter methylation was found in the CNE-1 cell
      line. CONCLUSIONS: Nasopharyngeal cancer may be a useful target for selective COX
      2 inhibition. The absence of promoter methylation may be a necessary component of
      COX-2 overexpression, and promoter methylation may be one of the mechanisms that
      regulate COX-2 expression.

PMID- 15723948
TI  - Mucosal wound healing in a rabbit model of subglottic stenosis: biochemical
      analysis of secretions.
AB  - OBJECTIVES: To build on work in laryngology and oral biology that suggests
      utility in the assay of secretions collected from wound sites as a predictive
      instrument to determine which infants will likely develop subglottic stenosis
      following endotracheal intubation and to document and describe the wound-healing
      process. DESIGN: Prospective, randomized design. INTERVENTION: Laser-induced
      subglottic injury was established in 3 rabbits. Secretions were collected from
      the subglottic region at 6 time points from days 4 to 21 following injury and
      from 4 uninjured control airways. The secretions were then subjected to enzyme
      linked immunoassays for interleukin 1 beta and prostaglandin E2. SUBJECTS: Three
      adult New Zealand white rabbits. MAIN OUTCOME MEASURES: Interleukin 1 beta and
      prostaglandin E2 levels. RESULTS: Measurable amounts of both mediators were
      obtained. Furthermore, different temporal patterns of expression were observed
      with interleukin 1 beta, showing increased levels on days 4 to 18, and with
      prostaglandin E2, showing increased levels on days 7 to 18. These results concur
      with emerging data regarding the role of each mediator in the wound-healing
      process. CONCLUSION: Although in its infancy, the analysis of secretions
      collected from the site of injury in the subglottis may have utility in the
      management of patients following intubation-related trauma.

PMID- 15723949
TI  - Impalement injuries of the pediatric craniofacial skeleton with retained foreign
      bodies.

PMID- 15723950
TI  - Internal jugular vein phlebectasia masquerading as an external laryngocele.

PMID- 15723951
TI  - Mandibular angle fractures and noncompression plating techniques.

PMID- 15723952
TI  - Miniplate repair of mandibular angle fractures.

PMID- 15723953
TI  - Compression plating of mandibular angle fractures.

PMID- 15723954
TI  - Pathology quiz case 1. Cervical neuroblastoma (NB).

PMID- 15723955
TI  - Pathology quiz case 2. Postirradiation sinonasal osteosarcoma.

PMID- 15723956
TI  - Radiology quiz case 1. Benign parotid cyst with associated facial paralysis.

PMID- 15723957
TI  - Radiology quiz case 2. Pleomorphic adenoma of minor salivary gland in the
      parapharyngeal space.

PMID- 15723958
TI  - Radiology quiz case 3. Giant intrasphenoidal aneurysm of the left internal
      carotid artery (ICA).

PMID- 15723959
TI  - Radiology quiz case 4. McCune-Albright syndrome.

PMID- 15723960
TI  - Reduced left ventricular functional reserve in hypertensive patients with
      preserved function at rest.
AB  - In many hypertensive patients, left ventricular pump function is normal at rest
      but abnormal during exercise. Myocardial dysfunction or altered left ventricular
      loading may be responsible for this finding. To verify the hypothesis of impaired
      myocardial functional reserve in the hypertensive heart, we assessed the response
      of stress-adjusted midwall shortening to graded, low-dose dobutamine infusion in
      hypertensive subjects with normal midwall shortening at rest. Sixty-five subjects
      (45 never treated hypertensive subjects and 20 normotensive volunteers comparable
      for age) received dobutamine at 1, 2, 3, 4, and 5 microg x kg(-1) x min(-1) for 5
      minute steps; within this range of infusion rates, heart rate and systemic blood
      pressure were stable. Two-dimensional, M-mode, and Doppler echocardiography were
      performed at baseline and at the end of each step. In normotensive controls,
      midwall shortening increased from baseline during 2 microg x kg(-1) x min(-1)
      dobutamine by an average of 16+/-4.5% (P<0.01); a value of 2 standard deviations
      below this mean response was taken as the lower limit of normal. In the
      hypertensive subjects, 24 had a normal midwall shortening response to dobutamine
      at this dose (group I) and 21 had a subnormal response (group II). Whereas blood
      pressure and left ventricular mass were similar in group II and group I, the
      former had greater relative wall thickness (P<0.01) than the latter. beta
      adrenergic stimulation by very-low-dose dobutamine unmasks subtle impairment of
      myocardial functional reserve in hypertensive subjects with normal myocardial
      performance at rest. This alteration seems to be related mainly to increase in
      left ventricular relative wall thickness.

PMID- 15723961
TI  - Endothelin, angiotensin, and oxidative stress in hypertension.

PMID- 15723962
TI  - Treating hypertension: when to say win.

PMID- 15723963
TI  - Morning surge and variability in blood pressure: a new therapeutic target?

PMID- 15723964
TI  - Effect of short-term supplementation of potassium chloride and potassium citrate
      on blood pressure in hypertensives.
AB  - Randomized trials have shown that increasing potassium intake lowers blood
      pressure. However, most previous trials used potassium chloride, whereas
      potassium in fruits and vegetables is not a chloride salt. It is unclear whether
      a nonchloride salt of potassium has a greater or lesser effect on blood pressure
      compared with potassium chloride. We performed a randomized crossover trial
      comparing potassium chloride with potassium citrate (96 mmol/d, each for 1 week)
      in 14 hypertensive individuals. At baseline, blood pressure was 151+/-16/93+/-7
      mm Hg with a 24-hour urinary potassium of 81+/-24 mmol. During the randomized
      crossover part of the study, blood pressure was 140+/-12/88+/-7 mm Hg with
      potassium chloride (24-hour urinary potassium: 164+/-36 mmol) and 138+/-12/88+/-6
      mm Hg with potassium citrate (24-hour urinary potassium: 160+/-33 mmol). These
      blood pressures were significantly lower compared with that at baseline; however,
      there was no significant difference in blood pressure between potassium chloride
      and potassium citrate, mean difference (95% confidence interval): 1.6 (-2.3 to
      5.6) mm Hg for systolic and 0.6 (-2.4 to 3.7) mm Hg for diastolic. Our results,
      in conjunction with the evidence from many previous trials that potassium
      chloride has a significant blood pressure-lowering effect, suggest that potassium
      citrate has a similar effect on blood pressure as potassium chloride. These
      results support other evidence for an increase in potassium intake and indicate
      that potassium does not need to be given in the form of chloride to lower blood
      pressure. Increasing the consumption of foods high in potassium is likely to have
      the same effect on blood pressure as potassium chloride.

PMID- 15723965
TI  - Cilostazol inhibits vascular smooth muscle cell growth by downregulation of the
      transcription factor E2F.
AB  - Neointimal formation, the leading cause of restenosis, is caused by proliferation
      of vascular smooth muscle cells (VSMCs). Patients with diabetes mellitus have
      higher restenosis rates after coronary angioplasty than nondiabetic patients.
      Cilostazol, a selective type 3 phosphodiesterase inhibitor, is currently used to
      treat patients with diabetic vascular complications. Cilostazol is a potent
      antiplatelet agent that inhibits VSMC proliferation. In the present study, we
      examine whether the antiproliferative effect of cilostazol on VSMCs is mediated
      by inhibition of an important cell cycle transcription factor, E2F. Cilostazol
      inhibited the proliferation of human VSMCs in response to high glucose in vitro
      and virtually abolished neointimal formation in rats subjected to carotid artery
      injury in vivo. Moreover, the compound suppressed high-glucose-induced E2F-DNA
      binding activity, and the expression of E2F1, E2F2, cyclin A, and PCNA proteins.
      These data suggest that the beneficial effects of cilostazol on high-glucose
      stimulated proliferation of VSMCs are mediated by the downregulation of E2F
      activity and expression of its downstream target genes, including E2F1, E2F2,
      cyclin A, and PCNA.

PMID- 15723966
TI  - Impact of obesity on 24-hour ambulatory blood pressure and hypertension.
AB  - The purpose of the present study was to determine the relationship between body
      mass index (BMI) and parameters derived from 24-hour ambulatory blood pressure
      monitoring including mean 24-hour daytime and nighttime systolic and diastolic
      blood pressures, 24-hour daytime and nighttime pulse pressure, mean 24-hour
      daytime and nighttime heart rate, dipping and nondipping status. 3216 outpatient
      subjects who visited our hypertension center and were never treated with
      antihypertensive medication underwent 24-hour blood pressure monitoring. BMI was
      significantly correlated with clinic systolic and diastolic blood pressures.
      Significant correlations were also found between BMI and mean 24-hour daytime and
      nighttime systolic blood pressure, 24-hour daytime and nighttime pulse pressure,
      and mean 24-hour daytime and nighttime heart rate. In multivariate regression
      analysis, clinic systolic, diastolic blood pressure, mean 24-hour systolic blood
      pressure, 24-hour pulse pressure, and high-density lipoprotein were independently
      correlated with BMI. The incidence of white coat hypertension was higher in
      overweight and obese patients than in normal weight subjects. Confirmed
      ambulatory blood pressure hypertension was also found to be higher in overweight
      and obese individuals compared with normal weight subjects. Our data also
      highlight the higher incidence of nondipping status in obesity. These findings
      suggest that obese patients had increased ambulatory blood pressure parameters
      and altered circadian blood pressure rhythm with increased prevalence of
      nondipping status.

PMID- 15723967
TI  - Inhibitory effects of AT1 receptor blocker, olmesartan, and estrogen on
      atherosclerosis via anti-oxidative stress.
AB  - The present study explored the possibility that estrogen enhances the inhibitory
      effect of an angiotensin II type-1 (AT1) receptor blocker (ARB), olmesartan, on
      atherosclerosis, focusing on oxidative stress using apolipoprotein E knockout
      mice (ApoEKO). After 6 weeks on a high-cholesterol diet, marked atherosclerotic
      lesion formation with an increase in oxidative stress, such as superoxide
      production, NAD(P)H oxidase activity and expression of p47phox mRNA and rac-1
      mRNA, were observed in the proximal aorta in both male and female ApoEKO mice,
      whereas these changes were less marked in female mice. Ovariectomy enhanced these
      parameters, the changes of which were reversed by 17beta-estradiol (80 microg/kg
      per day) replacement. Treatment with olmesartan (3 mg/kg per day) significantly
      inhibited oxidative stress and atherosclerosis, whereas its inhibitory effects
      were more marked in female than in male or ovariectomized mice. Smaller doses of
      olmesartan (0.5 mg/kg per day) or 17beta-estradiol (20 microg/kg per day) did not
      influence atherosclerosis and oxidative stress in ovariectomized mice, whereas co
      administration of olmesartan and 17beta-estradiol at these doses attenuated these
      parameters. An angiotensin-converting enzyme (ACE) inhibitor, temocapril, also
      inhibited atherosclerotic changes similarly to olmesartan. Moreover, angiotensin
      II-mediated activation of NAD(P)H oxidase in cultured vascular smooth muscle
      cells was attenuated by 17beta-estradiol. These results indicate that estrogen
      and an ARB synergistically attenuate atherosclerosis at least partly via
      inhibition of oxidative stress.

PMID- 15723968
TI  - Transforming growth factor-beta, 20-HETE interaction, and glomerular injury in
      Dahl salt-sensitive rats.
AB  - This study examined the role of transforming growth factor-beta (TGF-beta) in
      altering the glomerular permeability to albumin (P(alb)) during hypertension
      development in Dahl salt-sensitive (Dahl S) rats and whether TGF-beta acts by
      inhibiting the glomerular production of 20-HETE. The results indicate that the
      renal expression of TGF-beta doubles in Dahl S rats fed a high-salt diet for 7
      days, and this is associated with a marked rise in P(alb) from 0.19+/-0.04 to
      0.75+/-0.01 and changes in the ultrastructure of the glomerular filtration
      barrier. Chronic treatment of Dahl S rats with a TGF-beta neutralizing antibody
      prevented the increase in P(alb) and preserved the structure of glomerular
      capillaries. It had no effect on the rise in blood pressure produced by the high
      salt diet. In other studies, preincubation of glomeruli isolated from Sprague
      Dawley rats with TGF-beta1 (10 ng/mL) for 15 minutes increased P(alb) from 0.01+/
      0.01 to 0.60+/-0.02. This was associated with inhibition of the glomerular
      production of 20-HETE from 221+/-11 to 3.4+/-0.5 mug per 30 minutes per milligram
      of protein. Pretreatment of Sprague Dawley glomeruli with a stable analog of 20
      HETE, 20-hydroxyeicosa-5(Z), 14(Z)-dienoic acid, reduced baseline P(alb) and
      opposed the effects of TGF-beta to increase P(alb). These studies indicate that
      upregulation of the glomerular formation of TGF-beta may contribute to the
      development of proteinuria and glomerular injury early in hypertension
      development in Dahl S rats by increasing P(alb) through inhibition of the
      glomerular production of 20-HETE.

PMID- 15723969
TI  - Effect of treatment with candesartan or enalapril on subcutaneous small artery
      structure in hypertensive patients with noninsulin-dependent diabetes mellitus.
AB  - Structural alterations of subcutaneous small resistance arteries are associated
      with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes
      mellitus (NIDDM). However, no data are presently available about the effects of
      antihypertensive therapy on vascular structure in hypertensive patients with
      NIDDM. Therefore, we have investigated the effect of an angiotensin-converting
      enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker,
      candesartan cilexetil, on indices of subcutaneous small resistance artery
      structure in 15 patients with mild hypertension and NIDDM. Eight patients were
      treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg
      per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from
      the gluteal region at baseline and after 1 year of treatment. Small arteries were
      dissected and mounted on a micromyograph and the media-to-internal lumen ratio
      was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was
      assessed. A similar blood pressure-lowering effect and a similar reduction of the
      media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular
      collagen content was reduced and metalloproteinase-9 was increased by
      candesartan, but not by enalapril. Changes of circulating indices of collagen
      turnover and circulating matrix metalloproteinase paralleled those of vascular
      collagen. The 2 drugs equally improved endothelial function. In conclusion,
      antihypertensive treatment with drugs that inhibit the renin-angiotensin
      aldosterone system activity is able to correct, at least in part, alterations in
      small resistance artery structure in hypertensive patients with NIDDM.
      Candesartan may be more effective than enalapril in reducing collagen content in
      the vasculature.

PMID- 15723970
TI  - Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for
      a role of hypoxia-inducible factor-1 in bacterial infections.
AB  - BACKGROUND: Bartonella species are the only known bacterial pathogens causing
      vasculoproliferative disorders in humans (bacillary angiomatosis [BA]). Cellular
      and bacterial pathogenetic mechanisms underlying the induction of BA are largely
      unknown. METHODS AND RESULTS: Activation of hypoxia-inducible factor-1 (HIF-1),
      the key transcription factor involved in angiogenesis, was detected in Bartonella
      henselae-infected host cells in vitro by immunofluorescence, Western blotting,
      electrophoretic mobility shift, and reporter gene assays and by
      immunohistochemistry in BA tissue lesions in vivo. Gene microarray analysis
      revealed that a B henselae infection resulted in the activation of genes typical
      for the cellular response to hypoxia. HIF-1 was essential for B henselae-induced
      expression of vascular endothelial growth factor as shown by inhibition with the
      use of HIF-1-specific short-interfering RNA. Moreover, infection with B henselae
      resulted in increased oxygen consumption, cellular hypoxia, and decreased ATP
      levels in host cells. Infection with a pilus-negative variant of B henselae did
      not lead to cellular hypoxia or activation of HIF-1 or vascular endothelial
      growth factor secretion, suggesting a crucial role of this bacterial surface
      protein in the angiogenic reprogramming of the host cells. CONCLUSIONS: B
      henselae induces a proangiogenic host cell response via HIF-1. Our data provide
      for the first time evidence that HIF-1 may play a role in bacterial infections.

PMID- 15723971
TI  - Ventricular structure and function in aged dogs with renal hypertension: a model
      of experimental diastolic heart failure.
AB  - BACKGROUND: Heart failure (HF) with normal ejection fraction (diastolic HF [DHF])
      usually occurs in elderly patients with hypertension. The presence and
      significance of altered systolic and diastolic ventricular function in DHF is
      increasingly controversial. Our objective was to develop a clinically relevant
      large-animal model to better understand the pathophysiology of DHF. METHODS AND
      RESULTS: Ventricular structure and function were characterized in young control
      (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by
      renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was
      associated with normal left ventricular (LV) volume, increased LV mass, and
      myocardial fibrosis. LV relaxation was impaired in ExDHF (tau=53+/-6 ms) compared
      with OC (tau=35+/-3 ms; P<0.05) and YC (tau=33+/-6 ms; P<0.05) dogs. The percent
      diastole at which relaxation is complete was increased in ExDHF (116+/-30%)
      compared with OC (69+/-8%; P<0.05) and YC (35+/-5%; P<0.05) dogs. The coefficient
      of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic
      pressures increased dramatically in response to increases in blood pressure. End
      systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of
      myocardial performance was maintained. Arterial stiffness was increased in ExDHF
      dogs. CONCLUSIONS: Aged dogs with chronic hypertension exhibit LV hypertrophy and
      fibrosis with impaired LV relaxation but no increase in the coefficient of LV
      diastolic stiffness. LV systolic and arterial stiffness are increased, which may
      exacerbate load-dependent impairment of relaxation and contribute to increased
      filling pressures with hypertensive episodes. This model mimics many of the
      structural and functional characteristics described in the limited studies of
      human DHF and provides insight into the pathogenesis of DHF.

PMID- 15723972
TI  - Incidence, location, magnitude, and clinical correlates of saphenous vein graft
      calcification: an intravascular ultrasound and angiographic study.
AB  - BACKGROUND: The pattern of saphenous vein graft (SVG) calcification before
      percutaneous intervention has not been studied. METHODS AND RESULTS: We used
      diagnostic and preintervention intravascular ultrasound (IVUS) to determine the
      incidence and magnitude of SVG calcification in 334 SVG lesions in 274
      consecutive patients. Calcium was found in 133 SVGs (40%). Calcium was uniformly
      distributed among 48 lesion sites (14%), 43 proximal references (13%), and 42
      distal references (13%). Calcium was superficial in 20 (40%) and deep in 28
      (60%). Over the entire length of the SVGs, the maximum arc and length of calcium
      (in calcium-containing SVGs) averaged 174+/-107 degrees and 6.8+/-4.8 mm,
      respectively. In calcium-containing SVGs, lesion site arc and length of calcium
      measured 151+/-107 degrees and 4.1+/-3.7 mm, similar to the proximal and distal
      references (175+/-121 degrees and 4.0+/-2.3 mm and 177+/-121 degrees and 4.1+/
      2.5 mm, respectively). Graft age (7.5+/-4.7 versus 10.5+/-4.7 years, P<0.0001),
      insulin-treated diabetes mellitus (40% versus 60%, P=0.02), and tobacco use (44%
      versus 55%, P=0.06) were clinical independent predictors of SVG calcification.
      CONCLUSIONS: Sixty-five percent of calcium-containing SVGs had reference calcium
      in the absence of lesion calcium. Calcium was located primarily in SVG wall and
      not at the plaque. These data suggest that SVG calcium is not just part of lesion
      formation and maturation. SVG calcium occurred more commonly in older grafts, in
      insulin-treated diabetic patients, and in smokers.

PMID- 15723973
TI  - Worldwide survey on the methods, efficacy, and safety of catheter ablation for
      human atrial fibrillation.
AB  - BACKGROUND: The purpose of this study was to conduct a worldwide survey
      investigating the methods, efficacy, and safety of catheter ablation (CA) of
      atrial fibrillation (AF). METHODS AND RESULTS: A detailed questionnaire was sent
      to 777 centers worldwide. Data relevant to the study purpose were collected from
      181 centers, of which 100 had ongoing programs on CA of AF between 1995 and 2002.
      The number of patients undergoing this procedure increased from 18 in 1995 to
      5050 in 2002. The median number of procedures per center was 37.5 (range, 1 to
      600). Paroxysmal AF, persistent AF, and permanent AF were the indicated
      arrhythmias in 100.0%, 53.0%, and 20.0% of responding centers, respectively. The
      most commonly used techniques were right atrial compartmentalization between 1995
      and 1997, ablation of the triggering focus in 1998 and 1999, and electrical
      disconnection of multiple pulmonary veins between 2000 and 2002. Of 8745 patients
      completing the CA protocol in 90 centers, of whom 2389 (27.3%) required >1
      procedure, 4550 (52.0%; range among centers, 14.5% to 76.5%) became asymptomatic
      without drugs and another 2094 (23.9%; range among centers, 8.8% to 50.3%) became
      asymptomatic in the presence of formerly ineffective antiarrhythmic drugs over an
      11.6+/-7.7-month follow-up period. At least 1 major complication was reported in
      524 patients (6.0%). CONCLUSIONS: The findings of this survey provide a picture
      of the variable and evolving methods, efficacy, and safety of CA for AF as
      practiced in a large number of centers worldwide and may serve as a guide to
      clinicians considering therapeutic options in patients suffering from this
      arrhythmia.

PMID- 15723975
TI  - Magnetic resonance imaging during untreated ventricular fibrillation reveals
      prompt right ventricular overdistention without left ventricular volume loss.
AB  - BACKGROUND: Most out-of-hospital ventricular fibrillation (VF) is prolonged (>5
      minutes), and defibrillation from prolonged VF typically results in asystole or
      pulseless electrical activity. Recent visual epicardial observations in an open
      chest, open-pericardium model of swine VF indicate that blood flows from the high
      pressure arterial system to the lower-pressure venous system during untreated VF,
      thereby overdistending the right ventricle and apparently decreasing left
      ventricular size. Therefore, inadequate left ventricular stroke volume after
      defibrillation from prolonged VF has been postulated as a major contributor to
      the development of pulseless rhythms. METHODS AND RESULTS: Ventricular dimensions
      were determined by MRI for 30 minutes of untreated VF in a closed-chest, closed
      pericardium model in 6 swine. Within 1 minute of untreated VF, mean right
      ventricular volume increased by 29% but did not increase thereafter. During the
      first 5 minutes of untreated VF, mean left ventricular volume increased by 34%.
      Between 20 and 30 minutes of VF, stone heart occurred as manifested by dramatic
      thickening of the myocardium and concomitant substantial decreases in left
      ventricular volume. CONCLUSIONS: In this closed-chest swine model of VF,
      substantial right ventricular volume changes occurred early and did not result in
      smaller left ventricular volumes. The changes in ventricular volumes before the
      late development of stone heart do not explain why defibrillation from brief
      duration VF (<5 minutes) typically results in a pulsatile rhythm with return of
      spontaneous circulation, whereas defibrillation from prolonged VF (5 to 15
      minutes) does not.

PMID- 15723974
TI  - Alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular
      myocytes is mediated via thioredoxin-1-sensitive oxidative modification of thiols
      on Ras.
AB  - BACKGROUND: Alpha-adrenergic receptor (alphaAR)-stimulated hypertrophy in adult
      rat ventricular myocytes is mediated by reactive oxygen species-dependent
      activation of the Ras-Raf-MEK1/2-ERK1/2 signaling pathway. Because Ras is known
      to have redox-sensitive cysteine residues, we tested the hypothesis that alphaAR
      stimulated hypertrophic signaling is mediated via oxidative modification of Ras
      thiols. METHODS AND RESULTS: The effect of alphaAR stimulation on the number of
      free thiols on Ras was measured with biotinylated iodoacetamide labeling. alphaAR
      stimulation caused a 48% decrease in biotinylated iodoacetamide-labeled Ras that
      was reversed by dithiothreitol (10 mmol/L), indicating a decrease in the
      availability of free thiols on Ras as a result of an oxidative posttranslational
      modification. This effect was abolished by adenoviral overexpression of
      thioredoxin-1 (TRX1) and potentiated by the TRX reductase inhibitor azelaic acid.
      Likewise, alphaAR-stimulated Ras activation was abolished by TRX1 overexpression
      and potentiated by azelaic acid. TRX1 overexpression inhibited the alphaAR
      stimulated phosphorylation of MEK1/2, ERK1/2, and p90RSK and prevented cellular
      hypertrophy, sarcomere reorganization, and protein synthesis (versus beta
      galactosidase). Azelaic acid potentiated alphaAR-stimulated protein synthesis.
      Although TRX1 can directly reduce thiols, it also can scavenge ROS by increasing
      peroxidase activity. To examine this possibility, peroxidase activity was
      increased by transfection with catalase, and intracellular reactive oxygen
      species were measured with dichlorofluorescein diacetate fluorescence. Although
      catalase increased peroxidase activity approximately 20-fold, TRX1 had no effect.
      Likewise, the alphaAR-stimulated increase in dichlorofluorescein diacetate
      fluorescence was abolished with catalase but retained with TRX1. CONCLUSIONS:
      AlphaAR-stimulated hypertrophic signaling in adult rat ventricular myocytes is
      mediated via a TRX1-sensitive posttranslational oxidative modification of thiols
      on Ras.

PMID- 15723976
TI  - Targeted proteolysis sustains calcineurin activation.
AB  - BACKGROUND: Calcineurin (CnA) is important in the regulation of myocardial
      hypertrophy. We demonstrated that targeted proteolysis of the CnA autoinhibitory
      domain under pathological myocardial workload leads to increased CnA activity in
      human myocardium. Here, we investigated the proteolytic mechanism leading to
      activation of CnA. METHODS AND RESULTS: In patients with diseased myocardium, we
      found strong nuclear translocation of CnA. In contrast, in normal human
      myocardium, there was a cytosolic distribution of CnA. Stimulation of rat
      cardiomyocytes with angiotensin (Ang) II increased calpain activity significantly
      (433+/-11%; P<0.01; n=6) and caused proteolysis of the autoinhibitory domain of
      CnA. Inhibition of calpain by a membrane-permeable calpain inhibitor prevented
      proteolysis. We identified the cleavage site of calpain in the human CnA sequence
      at amino acid 424. CnA activity was increased after Ang II stimulation (310+/
      29%; P<0.01; n=6) and remained high after removal of Ang II (214+/-17%; P<0.01;
      n=6). Addition of a calpain inhibitor to the medium decreased CnA activity (110+/
      19%; P=NS; n=6) after removal of Ang II. Ang II stimulation of cardiomyocytes
      also translocated CnA into the nucleus as demonstrated by immunohistochemical
      staining and transfection assays with GFP-tagged CnA. Calpain inhibition and
      therefore suppression of calpain-mediated proteolysis of CnA enabled CnA exit
      from the nucleus. CONCLUSIONS: Ang II stimulation of cardiomyocytes increased
      calpain activity, leading to proteolysis of the autoinhibitory domain of CnA.
      This causes an increase in CnA activity and results in nuclear translocation of
      CnA. Loss of the autoinhibitory domain renders CnA constitutively nuclear and
      active, even after removal of the hypertrophic stimulus.

PMID- 15723977
TI  - Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents:
      three-year results of the RAVEL trial.
AB  - BACKGROUND: The use of sirolimus-eluting coronary stents has been associated with
      a nearly complete elimination of restenosis at 6 months and with a very low 1
      year incidence of major adverse cardiac events (MACE). This analysis examined
      whether these beneficial effects persist over the longer term. METHODS AND
      RESULTS: This multicenter trial randomly assigned 238 patients to
      revascularization of single, de novo, native coronary artery lesions with
      sirolimus-eluting versus conventional bare-metal stents. Survival free from
      target lesion revascularization (TLR), target vessel failure (TVF), and MACE up
      to 3 years of follow-up was compared between the 2 treatment groups. Complete
      data sets were available in 94.2% of patients treated with sirolimus-eluting
      stents and in 94.1% of patients randomized to the control group. The cumulative 1
      , 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR
      and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent
      group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF
      in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at
      3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents
      versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient
      treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36
      months. CONCLUSIONS: Treatment of de novo coronary stenosis with sirolimus
      eluting stents was associated with a sustained clinical benefit and very low
      rates of TLR and of other MACE up to 3 years after device implantation.

PMID- 15723978
TI  - Noninvasive assessment of blood flow based on magnetic resonance global coherent
      free precession.
AB  - BACKGROUND: Magnetic resonance global coherent free precession (GCFP) is a new
      technique that produces cine projection angiograms directly analogous to those of
      x-ray angiography noninvasively and without a contrast agent. In this study, we
      compared GCFP blood flow with "gold standards" to determine the accuracy of
      noninvasive GCFP blood flow measurements. METHODS AND RESULTS: The relationship
      between GCFP blood flow and true blood flow defined by invasive ultrasonic flow
      probe and by phase contrast velocity encoded MRI (VENC) was studied in
      anesthetized dogs (n=6). Blood flow was controlled by use of a hydraulic occluder
      around the left iliac artery. GCFP images were acquired by selectively exciting
      the abdominal aorta and visualizing temporal blood flow into the iliac arteries.
      GCFP flow was similar to ultrasonic blood flow at baseline (131.3+/-44.8 versus
      114.8+/-34.2 mL/min), during occlusion (10.8+/-5.1 versus 6.5+/-7.2 mL/min),
      during reactive hyperemia (191.4+/-100.7 versus 260.3+/-138.7 mL/min), during the
      new resting state (135.5+/-52.4 versus 117.8+/-24.1 mL/min), and during partial
      occlusion (61.4+/-36.4 versus 49.3+/-13.1 mL/min, P=NS for all). Results
      comparing GCFP flow with VENC were similar. Statistical analysis revealed that
      GCFP flow was related to mean blood flow assessed by the flow probe (P<0.0001)
      and by VENC (P<0.0001). In the control right iliac artery, conversely, GCFP
      measurements were unaffected throughout all left iliac interventions (P=NS).
      CONCLUSIONS: GCFP blood flow is linearly related to true blood flow for a
      straight, cylindrical blood vessel without branches. Although more complex
      geometries imply a qualitative rather than a quantitative relationship, the data
      nevertheless suggest that GCFP may serve as the basis for a new form of
      noninvasive stress testing.

PMID- 15723979
TI  - Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent
      antihypertensive efficacy and placebo-like tolerability in hypertensive patients.
AB  - BACKGROUND: Stopping the detrimental effects of the renin-angiotensin system at
      the most upstream point of the cascade offers theoretical advantages for
      cardiovascular protection. This study compares the antihypertensive efficacy and
      safety of the novel oral renin inhibitor aliskiren with placebo and an active
      comparator. METHODS AND RESULTS: The study was a randomized, multicenter, double
      blind, placebo-controlled, active-comparator 8-week trial in patients with mild
      to-moderate hypertension (mean sitting diastolic blood pressure [DBP] > or =95
      and <110 mm Hg). After a 2-week, single-blind placebo run-in, 652 patients were
      randomized to receive double-blind treatment with once-daily oral doses of
      aliskiren (150, 300, or 600 mg), irbesartan 150 mg, or placebo. Aliskiren 150,
      300, and 600 mg effectively lowered both trough mean sitting DBP and systolic
      blood pressure (SBP) (P<0.001 versus placebo for both variables). The least
      squares mean reductions in trough DBP were 9.3+/-0.8, 11.8+/-0.8, and 11.5+/-0.8
      mm Hg, respectively, versus 6.3+/-0.8 mm Hg for placebo, and the least-squares
      mean reductions in trough SBP were 11.4+/-1.3, 15.8+/-1.2, and 15.7+/-1.2 mm Hg,
      respectively, versus 5.3+/-1.2 mm Hg for placebo. The antihypertensive effect of
      aliskiren 150 mg was comparable to that of irbesartan 150 mg (8.9+/-0.7 and
      12.5+/-1.2 mm Hg, least-squares reduction in mean sitting DBP and SBP,
      respectively, for irbesartan). Aliskiren 300 and 600 mg lowered mean sitting DBP
      significantly more than irbesartan 150 mg (P<0.05). Aliskiren showed safety and
      tolerability comparable to those of placebo and irbesartan; the incidence of
      adverse events and number of patients discontinuing therapy were similar in all
      groups. CONCLUSIONS: Once-daily oral treatment with aliskiren lowers blood
      pressure effectively, with a safety and tolerability profile comparable to that
      of irbesartan and placebo, in patients with mild-to-moderate hypertension.
      Aliskiren 150 mg is as effective as irbesartan 150 mg in lowering blood pressure.

PMID- 15723980
TI  - Predictors of new-onset diastolic and systolic hypertension: the Framingham Heart
      Study.
AB  - BACKGROUND: Factors leading differentially to the development of isolated
      diastolic (IDH), systolic-diastolic (SDH), and isolated systolic (ISH)
      hypertension are poorly understood. We examined the relations of blood pressure
      (BP) and clinical risk factors to the new onset of the 3 forms of hypertension.
      METHODS AND RESULTS: Participants in the Framingham Heart Study were included if
      they had undergone 2 biennial examinations between 1953 and 1957 and were free of
      antihypertensive therapy and cardiovascular disease. Compared with optimal BP
      (SBP <120 and DBP <80 mm Hg), the adjusted hazard ratios (HRs) for developing new
      onset IDH over the ensuing 10 years were 2.75 for normal BP, 3.29 for high-normal
      BP (both P<0.0001), 1.31 (P=0.40) for SDH, and 0.61 (P=0.36) for ISH. The HRs of
      developing new-onset SDH were 3.32, 7.96, 7.10, and 23.12 for the normal BP, high
      normal BP, ISH, and IDH groups, respectively (all P<0.0001). The HRs of
      developing ISH were 3.26 for normal and 4.82 for high-normal BP (both P<0.0001),
      1.39 (P=0.24) for IDH, and 1.69 (P<0.01) for SDH. Increased body mass index (BMI)
      during follow-up predicted new-onset IDH and SDH. Other predictors of IDH were
      younger age, male sex, and BMI at baseline. Predictors of ISH included older age,
      female sex, and increased BMI during follow-up. CONCLUSIONS: Given the propensity
      for increased baseline BMI and weight gain to predict new-onset IDH and the high
      probability of IDH to transition to SDH, it is likely that IDH is not a benign
      condition. ISH arises more commonly from normal and high-normal BP than from
      "burned-out" diastolic hypertension.

PMID- 15723981
TI  - Cost-effectiveness of eplerenone compared with placebo in patients with
      myocardial infarction complicated by left ventricular dysfunction and heart
      failure.
AB  - BACKGROUND: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure
      Efficacy and Survival Study (EPHESUS), aldosterone blockade with eplerenone
      decreased mortality in patients with left ventricular systolic dysfunction and
      heart failure after acute myocardial infarction. The present study was performed
      to evaluate the cost-effectiveness of eplerenone compared with placebo in these
      patients. METHODS AND RESULTS: A total of 6632 patients with left ventricular
      systolic dysfunction and heart failure after acute myocardial infarction were
      randomized to eplerenone or placebo and followed up for a mean of 16 months. The
      coprimary end points were all-cause mortality and the composite of cardiovascular
      mortality/cardiovascular hospitalization. The evaluation of resource use included
      hospitalizations, outpatient services, and medications. Eplerenone was priced at
      the average wholesale price, 3.60 dollars per day. Survival beyond the trial
      period was estimated from data from the Framingham Heart Study, the Saskatchewan
      Health database, and the Worcester Heart Attack Registry. The incremental cost
      effectiveness of eplerenone in cost per life-year and quality-adjusted life-year
      gained compared with placebo was estimated. The number of life-years gained with
      eplerenone was 0.1014 based on Framingham (95% CI, 0.0306 to 0.1740), 0.0636 with
      Saskatchewan (95% CI, 0.0229 to 0.1038), and 0.1337 with Worcester (95% CI,
      0.0438 to 0.2252) data. Cost was 1391 dollars higher over the trial period in the
      eplerenone arm (95% CI, 656 to 2165) because of drug cost. The incremental cost
      effectiveness ratio was 13,718 dollars per life-year gained with Framingham
      (96.7% under 50,000 dollars per life-year gained), 21,876 dollars with
      Saskatchewan, and 10,402 dollars with Worcester. CONCLUSIONS: Eplerenone compared
      with placebo in the treatment of heart failure after acute myocardial infarction
      is effective in reducing mortality and is cost-effective in increasing years of
      life by commonly used criteria.

PMID- 15723982
TI  - Troponin elevation after percutaneous coronary intervention directly represents
      the extent of irreversible myocardial injury: insights from cardiovascular
      magnetic resonance imaging.
AB  - BACKGROUND: Although troponin elevation after percutaneous coronary intervention
      (PCI) is common, uncertainties remain about the mechanisms of its release and its
      relationship to the volume of myocardial tissue loss. Delayed-enhancement MRI of
      the heart has been shown to reliably quantify areas of irreversible myocardial
      injury. To investigate the quantitative relationship between irreversible injury
      and cardiac troponin release, we studied the incidence and extent of new
      irreversible injury in patients undergoing PCI and correlated it to
      postprocedural changes in cardiac troponin I. METHODS AND RESULTS: Fifty patients
      undergoing PCI were studied with preprocedural and postprocedural (24 hours)
      delayed-enhancement MRI for assessment of new irreversible myocardial injury.
      Cardiac troponin I measurements were obtained before PCI and 24 hours after PCI.
      Of these 50 patients, 24 underwent a further third MRI scan at a median of 8
      months after the procedure. Mean patient age was 64+/-12 years. After the
      procedure, 14 patients (28%) had evidence of new myocardial hyperenhancement,
      with a mean mass of 6.0+/-5.8 g, or 5.0+/-4.8% of total left ventricular mass.
      All of these patients had raised troponin I levels (range 1.0 to 9.4 mug/L).
      Thirty-four patients (68%) had no elevated troponin I and no evidence of new
      myocardial necrosis on MRI. There was a strong correlation between the rise in
      troponin I measurements at 24 hours and mean mass of new myocardial
      hyperenhancement, both early (r=0.84; P<0.001) and late (r=0.71; P<0.001) after
      PCI, although there was a trend for a reduction in the size of PCI-induced
      myocardial injury in the late follow-up scan (P=0.07). CONCLUSIONS: In the
      setting of PCI, patients demonstrating postprocedural elevation in troponin I
      have evidence of new irreversible myocardial injury on delayed-enhancement MRI.
      The magnitude of this injury correlates directly with the extent of troponin
      elevation.

PMID- 15723983
TI  - Plaque instability frequently occurs days or weeks before occlusive coronary
      thrombosis: a pathological thrombectomy study in primary percutaneous coronary
      intervention.
AB  - BACKGROUND: Acute ST-elevation myocardial infarction (STEMI) is caused by sudden
      occlusive coronary thrombosis, after plaque disruption; however, a considerable
      time interval between plaque disturbance and the onset of symptoms has been
      suggested. We therefore studied the age of intracoronary thrombi, aspirated
      during angioplasty in patients with acute STEMI. METHODS AND RESULTS:
      Percutaneous intracoronary thrombectomy during angioplasty was performed in 211
      consecutive STEMI patients within 6 hours after onset of anginal symptoms. The
      aspirated material was histologically screened on thrombus and plaque components,
      and thrombus age was classified as fresh (<1 day), lytic thrombus (1 to 5 days),
      and organized thrombus (>5 days). In all patients, intracoronary-derived material
      was retrieved in the filter of the collection bottle. Thrombus was identified in
      199 (95%) of 211 patients. In 12 patients (5%), only plaque components were
      identified, and in 85 patients (41%), both thrombus and plaque material were
      aspirated. In 18 (9%) of 199 patients, the thrombus was organized, and in 70
      patients (35%), the thrombus showed lytic changes, whereas in 98 (49%), a
      completely fresh thrombus was found. In 14 (7%) of 199 patients, the thrombus
      showed combined features of both fresh thrombus and organized thrombus.
      CONCLUSIONS: In at least 50% of patients with acute STEMI, coronary thrombi were
      days or weeks old. This indicates that sudden coronary occlusion is often
      preceded by a variable period of plaque instability and thrombus formation,
      initiated days or weeks before onset of symptoms.

PMID- 15723984
TI  - Artifact-free coronary magnetic resonance angiography and coronary vessel wall
      imaging in the presence of a new, metallic, coronary magnetic resonance imaging
      stent.
AB  - BACKGROUND: Coronary in-stent restenosis cannot be directly assessed by magnetic
      resonance angiography (MRA) because of the local signal void of currently used
      stainless steel stents. The aim of this study was to investigate the potential of
      a new, dedicated, coronary MR imaging (MRI) stent for artifact-free, coronary MRA
      and in-stent lumen and vessel wall visualization. METHODS AND RESULTS: Fifteen
      prototype stents were deployed in coronary arteries of 15 healthy swine and
      investigated with a double-oblique, navigator-gated, free-breathing, T2-prepared,
      3D cartesian gradient-echo sequence; a T2-prepared, 3D spiral gradient-echo
      sequence; and a T2-prepared, 3D steady-state, free-precession coronary MRA
      sequence. Furthermore, black-blood vessel wall imaging by a dual-inversion
      recovery, turbo spin-echo sequence was performed. Artifacts of the stented vessel
      segment and signal intensities of the coronary vessel lumen inside and outside
      the stent were assessed. With all investigated sequences, the vessel lumen and
      wall could be visualized without artifacts, including the stented vessel segment.
      No signal intensity alterations inside the stent when compared with the vessel
      lumen outside the stent were found. CONCLUSIONS: The new, coronary MRI stent
      allows for completely artifact-free coronary MRA and vessel wall imaging.

PMID- 15723985
TI  - Endothelial progenitor cells are rapidly recruited to myocardium and mediate
      protective effect of ischemic preconditioning via "imported" nitric oxide
      synthase activity.
AB  - BACKGROUND: The function of bone marrow-derived endothelial progenitor cells
      (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and
      the capacity of these cells to contribute significantly to new blood vessels
      remains controversial. The possibility that EPCs could act as reservoirs of
      cytokines has been implied by several observations; however, a specific role for
      cytokine delivery has not been identified. METHODS AND RESULTS: We performed a
      series of experiments that revealed the rapid recruitment of EPCs to the
      myocardium by very short periods of ischemia, so-called ischemic preconditioning.
      The recruited EPCs express an array of potentially cardioprotective cytokines
      including nitric oxide synthase isoforms. Bone marrow transplantation studies,
      using donor marrow null for nitric oxide synthase isoforms, revealed that both
      endothelial and inducible nitric oxide synthase derived from bone marrow cells
      play essential roles in the cardioprotective effect that normally occurs after
      ischemic preconditioning. CONCLUSIONS: These findings provide novel insights
      about the role of bone marrow-derived cells in ischemic preconditioning and also
      reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and
      chronic ischemic injury.

PMID- 15723987
TI  - Images in cardiovascular medicine. Sinus of valsalva rupture with dissection into
      the interventricular septum: diagnosis by echocardiography and magnetic resonance
      imaging.

PMID- 15723986
TI  - Trafficking of the membrane type-1 matrix metalloproteinase in ischemia and
      reperfusion: relation to interstitial membrane type-1 matrix metalloproteinase
      activity.
AB  - BACKGROUND: The matrix metalloproteinases (MMPs) contribute to regional
      remodeling after prolonged periods of ischemia and reperfusion (I/R), but
      specific MMP types activated during this process remain poorly understood. A
      novel class, the membrane-type MMPs (MT-MMPs), has been identified in the
      myocardium, but activity of these MMP types has not been assessed in vivo,
      particularly during I/R. METHODS AND RESULTS: Pigs (30 kg, n=8) were instrumented
      with microdialysis catheters to measure MT1-MMP activity in both ischemic and
      nonischemic (remote) myocardium. A validated MT1-MMP fluorogenic substrate was
      infused through the microdialysis system, and changes in fluorescence were
      reflective of MT1-MMP activity at steady state, during ischemia (90 minutes), and
      during reperfusion (120 minutes). At peak ischemia, MT1-MMP activity was
      increased by >40% in the ischemic region, with no change in the remote region,
      which persisted with reperfusion (P<0.05). After I/R, MT1-MMP abundance was
      increased by >50% (P<0.05). Differential centrifugation revealed that the
      endosomal fraction (which contains subcellular organelles) within the ischemic
      myocardium was associated with a >135% increase in MT1-MMP (P<0.05). Furthermore,
      in an isolated left ventricular myocyte model of I/R, hypoxia (simulated
      ischemia) induced a >70% increase in MT1-MMP abundance in myocytes, and confocal
      microscopy revealed MT1-MMP internalization during this time period and
      reemergence to the membrane with reperfusion. CONCLUSIONS: These unique results
      demonstrate that a specific MMP type, MT1-MMP, is increased in abundance and
      activity with I/R and is likely attributed, at least in part, to changes in
      intracellular trafficking.

PMID- 15723988
TI  - Calcium, magnesium, and oxidative stress in hyperaldosteronism.

PMID- 15723989
TI  - The bicuspid aortic valve: adverse outcomes from infancy to old age.

PMID- 15723990
TI  - The Department of Surgery University of North Carolina School of Medicine, Chapel
      Hill.

PMID- 15723991
TI  - Smoking is a risk factor for incisional hernia.
AB  - HYPOTHESIS: A number of risk factors for incisional hernia have been identified,
      but the pathogenesis remains unclear. Based on previous findings of smoking as a
      risk factor for wound complications and recurrence of groin hernia, we studied
      whether smoking is associated with incisional hernia. DESIGN: Cohort study.
      Clinical follow-up study for incisional hernia 33 to 57 months following
      laparotomy for gastrointestinal disease. Variables predictive for incisional
      hernia were assessed by multiple regression analysis. SETTING: Department of
      Surgery, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
      PATIENTS: All 916 patients undergoing laparotomy from 1997 through 1998. Surgeons
      performed clinical examination in 310 patients; patients who failed to meet for
      examination, died, or were lost to follow-up were excluded. MAIN OUTCOME
      MEASURES: Thirty-four variables related to patient history, preoperative clinical
      condition, operative severity and findings, and the surgeon's training. RESULTS:
      The incidence of incisional hernia was 26% (81/310). Smokers had a 4-fold higher
      risk of incisional hernia (odds ratio [OR], 3.93 [95% confidence interval (CI),
      1.82-8.49]) independent of other risk factors and confounders. Relaparotomy was
      the strongest factor associated with hernia (OR, 5.89 [95% CI, 1.78-19.48]).
      Other risk factors were postoperative wound complications (OR, 3.91 [95% CI, 1.99
      7.66]), age (OR, 1.04 [95% CI, 1.02-1.06]), and male sex (OR, 2.17 [95% CI, 1.21
      3.91]). CONCLUSION: Smoking is a significant risk factor for incisional hernia in
      line with relaparotomy, postoperative wound complications, older age, and male
      sex.

PMID- 15723992
TI  - Effect of core-needle biopsy vs fine-needle aspiration on pathologic measurement
      of tumor size in breast cancer.
AB  - HYPOTHESIS: Core-needle biopsy (CNB) and fine-needle aspiration (FNA) play an
      important role in the initial diagnosis of breast cancer. However, CNB might
      alter the size of the tumor, which might subsequently change its pathologic stage
      and thus affect the decision about adjuvant chemotherapy. PATIENTS: Between
      January 2000 and May 2002, we studied 291 patients with invasive carcinoma lesion
      in a retrospective analysis. One hundred ninety-nine patients underwent
      ultrasonography-guided CNB. Ninety-two patients had FNA before surgical
      manipulation. MAIN OUTCOME MEASURES: The clinically measured tumor size using
      ultrasonography was compared with the pathologic tumor size in both the CNB and
      FNA groups. The difference in each group was determined and analyzed using a t
      test. The mean +/- SD preoperative ultrasonographically measured size in the CNB
      group was 2.09 +/- 1.06 cm and in the FNA group, 2.16 +/- 0.92 cm (no significant
      difference). The pathologic measurement of the lesion on surgical specimens
      revealed that the mean pathologic tumor size was 2.09 +/- 0.90 cm in the CNB
      group and 2.36 +/- 0.92 cm in the FNA group. The changes in size from
      preoperative measurements by ultrasonography to pathologic measurements on
      surgical specimens were greater in the CNB group (0.003 +/- 0.65 cm) than in the
      FNA group (0.20 +/- 0.39 cm; P = .001). CONCLUSIONS: Although the reduction in
      tumor size might be small with patients who undergo CNB, it must be considered
      when deciding adjuvant treatment, especially for tumor sizes on the "borderline"
      in establishing the indication for and the type of adjuvant treatment.

PMID- 15723993
TI  - Beneficial effects of ischemic preconditioning in patients undergoing
      hepatectomy: the role of neutrophils.
AB  - HYPOTHESES: Temporary vascular clampage (Pringle maneuver) during liver surgery
      can cause ischemia-reperfusion injury. In this process, activation of
      polymorphonuclear leukocytes (PMNLs) might play a major role. Thus, we
      investigated the effects of hepatic ischemic preconditioning on PMNL functions.
      DESIGN: Prospective randomized study. Patients who underwent partial liver
      resection were randomly assigned to 3 groups: group 1 without Pringle maneuver;
      group 2 with Pringle maneuver, and group 3 with ischemic preconditioning using 10
      minutes of ischemia and 10 minutes of reperfusion prior to Pringle maneuver for
      resection. SETTING: University hospital, Munich, Germany. PATIENTS: Seventy-five
      patients underwent hepatic surgery mostly owing to metastasis. MAIN OUTCOME
      MEASURES: Perioperative factors for PMNL activation, inflammation, and
      postoperative hepatocellular integrity. RESULTS: Ischemia-reperfusion of the
      human liver (mean +/- SD time to perform the Pringle maneuver, 35.5 +/- 2.6
      minutes) caused (1) a decrease in the number of circulating PMNLs, (2) their
      intrahepatic sequestration, (3) their systemic activation, and (4) a significant
      correlation between the degree of their postischemic activation and the
      postoperative rise in liver enzyme serum levels. In parallel, cytokines with
      proinflammatory and chemotactic properties were released reaching the highest
      values when stimulation of PMNLs was most pronounced. When ischemic
      preconditioning preceded the Pringle maneuver, activation of PMNLs and cytokine
      plasma levels was reduced as evidenced by the attenuation of superoxide anion
      production, beta(2)-integrin up-regulation, and interleukin 8 serum
      concentrations, followed by a significant reduction in serum alanine
      aminotransferase levels on the first and second postoperative days. CONCLUSIONS:
      These results demonstrate in humans that ischemic preconditioning reduces
      activation of PMNLs elicited by the Pringle maneuver. The down-regulation of
      potentially cytotoxic functions of PMNLs might be one of yet unknown important
      pathways that altogether mediate protection by ischemic preconditioning.

PMID- 15723994
TI  - Resident operative experience during the transition to work-hour reform.
AB  - HYPOTHESIS: The operative volume of chief residents would decrease with work-hour
      reform by the Accreditation Council for Graduate Medical Education (ACGME).
      DESIGN: Mixed-design study performed during July and December 2003. Collected
      data were from programs experimenting with work-hour reform and programs that had
      not yet implemented reform. New York programs were also included. SETTING:
      University-, community/university-, and community-based surgical residency
      programs. OTHER PARTICIPANTS: Telephone conversations occurred with 10 randomly
      selected program directors. MAIN OUTCOME MEASURES: Operative logs from chief
      residents graduating in 2002 and 2003 and a survey requesting information on
      programmatic changes. RESULTS: Of the 80 programs that responded, statistical
      analyses revealed the following findings: (1) there were no significant
      differences in the operative volume of chief residents based on work-hour model,
      program setting, or graduating class; (2) there was no significant difference in
      chiefs' operative volume between programs that experimented with work-hour reform
      and programs that did not experiment with work-hour reform during 2002-2003; (3)
      there was no relationship found between work hours and volume of operative cases;
      and (4) there was an inverse relationship found between work hours and operative
      volume for residents in New York programs. CONCLUSION: Several correlates must be
      considered for effective assessment and evaluation of the impact of work-hour
      reform on surgical training and education.

PMID- 15723995
TI  - Applicability of tissue aspirate for quick parathyroid hormone assay to confirm
      parathyroid tissue identity during parathyroidectomy for primary
      hyperparathyroidism.
AB  - HYPOTHESIS: Intraoperative quick parathyroid hormone (PTH) assay for tissue
      aspirate facilitates the confirmation of parathyroid tissue identity and allows a
      more selective use of frozen section examination during parathyroidectomy for
      primary hyperparathyroidism. DESIGN: A retrospective review of a prospective
      protocol of the applicability and accuracy of quick PTH assay for tissue aspirate
      as a biochemical frozen section tool. SETTING: A university hospital department
      of surgery. PATIENTS: Quick PTH assay for aspirate obtained from suspected
      parathyroid gland excised during parathyroidectomy for primary
      hyperparathyroidism. MAIN OUTCOME MEASURES: The accuracy of this biochemical
      identification of parathyroid tissue identity was correlated with histological
      examination and outcome. RESULTS: Quick PTH assay was performed for aspirate from
      at least 1 excised parathyroid gland in 122 (98%) of 125 patients while 13
      patients (10%) had PTH aspirate for nonparathyroid tissues including thyroid (n =
      10), thymic (n = 2) and lymphatic (n = 1) tissues. Frozen section examination was
      performed for 15 patients (12%), including the 3 patients who did not undergo
      tissue aspirate for quick PTH assay. All except 3 patients had an aspirate assay
      value of greater than 1500 pg/mL (range, 625 to >1500 pg/mL) for parathyroid
      tissue while the value of PTH aspirate for nonparathyroid tissue ranged from 27
      to 229 pg/mL (median, 72 pg/mL) in 13 patients. The median size of abnormal
      parathyroid gland was 70 to 15,000 mg (median, 775 mg). CONCLUSIONS: With the
      availability of quick PTH assay, tissue aspirate for PTH assay can be adopted as
      an alternative to traditional frozen section examination to confirm parathyroid
      gland identity. Frozen section examination can be employed more selectively.

PMID- 15723996
TI  - Predictors of mortality and limb loss in necrotizing soft tissue infections.
AB  - HYPOTHESIS: Necrotizing soft tissue infections are associated with a high
      mortality rate. We hypothesize that specific predictors of limb loss and
      mortality in patients with necrotizing soft tissue infection can be identified on
      hospital admission. DESIGN: A retrospective cohort study. SETTING: A tertiary
      care center. PATIENTS: Patients with a diagnosis of necrotizing soft tissue
      infection during a 5-year period (1996-2001) were included. Patients were
      identified with International Classification of Diseases, Ninth Revision hospital
      discharge diagnosis codes, and diagnosis was confirmed by medical record review.
      INTERVENTIONS: Standard current treatment including early and scheduled repeated
      debridement, broad-spectrum antibiotics, and physiologic and nutritional support
      was given to all patients. MAIN OUTCOME MEASURES: Limb loss and mortality.
      RESULTS: One hundred sixty-six patients were identified and included in the
      study. The overall mortality rate was 16.9%, and limb loss occurred in 26% of
      patients with extremity involvement. Independent predictors of mortality included
      white blood cell count greater than 30 000 x 10(3)/microL, creatinine level
      greater than 2 mg/dL (176.8 micromol/L), and heart disease at hospital admission.
      Independent predictors of limb loss included heart disease and shock (systolic
      blood pressure <90 mm Hg) at hospital admission. Clostridial infection was an
      independent predictor for both limb loss (odds ratio, 3.9 [95% confidence
      interval, 1.1-12.8]) and mortality (odds ratio, 4.1 [95% confidence interval, 1.3
      12.3]) and was highly associated with intravenous drug use and a high rate of
      leukocytosis on hospital admission. The latter was found to be a good variable in
      estimating the probability of death. CONCLUSIONS: Clostridial infection is
      consistently associated with poor outcome. This together with the independent
      predictors mentioned earlier should aid in identifying patients on hospital
      admission who may benefit from more aggressive and novel therapeutic approaches.

PMID- 15723997
TI  - Extracolonic manifestations of familial adenomatous polyposis after
      proctocolectomy.
AB  - HYPOTHESIS: Extracolonic manifestations have a major effect on the morbidity and
      mortality of patients with familial adenomatous polyposis following
      proctocolectomy. DESIGN: Case review study. SETTING: Colorectal unit, university
      affiliated hospital. PATIENTS: Fifty patients (25 males and 25 females) with
      familial adenomatous polyposis WHO underwent proctocolectomy between January 1988
      and October 2003. INTERVENTIONS: Ileal pouch-anal anastomosis (n = 41), Kock
      pouch (n = 1), end ileostomy (n = 6). Two patients underwent total colectomy with
      an ileorectal anastomosis. MAIN OUTCOME MEASURES: Clinical follow-up and
      telephone interview; contact with clinicians following up patients elsewhere.
      RESULTS: The patients' median age at surgery was 33 years. The mean length of
      follow-up was 74 months. Four patients were lost to follow-up. Extracolonic
      manifestations were diagnosed in 38 patients (76%). Twelve patients had 14
      desmoid tumors: 7 were treated surgically and 7 medically (these patients
      received celecoxib and tamoxifen citrate therapy). Of the 41 patients who
      underwent upper gastrointestinal tract endoscopy, 11 developed duodenal and/or
      ampullary adenomas. Three patients had endoscopic polypectomy and 1 underwent a
      Whipple operation. Among the 29 patients who underwent pouchoscopy, 5 had pouch
      adenomas and 3 had adenomas that were found in the rectal stump. Two patients
      died--one of a huge mesenteric desmoid tumor and the other of an aggressive
      mesenteric malignant fibrous histiocytoma. CONCLUSIONS: Long-term morbidity and
      mortality were strongly related to the development of mesenteric tumors and
      ampullary-duodenal polyps. Early detection of desmoid tumors, duodenal, pouch,
      and rectal cuff adenomas by periodic computed tomography, gastroduodenoscopy, and
      pouchoscopy, respectively, may allow control by medical therapy, endoscopy, or
      limited surgical procedures. In most patients control of desmoid tumors was
      achieved using a combination of celecoxib and tamoxifen citrate therapy.

PMID- 15723998
TI  - Impact of advanced age on weight loss and health benefits after laparoscopic
      gastric bypass.
AB  - BACKGROUND: Advanced age is considered a relative contraindication to primary
      bariatric surgery at some institutions. As life expectancy is steadily increasing
      and quality of life is improving in our elderly population, we may need to
      reconsider the health benefits that obese elderly patients can obtain from
      bariatric surgery. Therefore, we examine the operative outcomes, weight loss,
      reduction of comorbidities, and medication requirements in patients older than 60
      years compared with those younger than 60 years undergoing laparoscopic Roux-en-Y
      gastric bypass. HYPOTHESIS: The null hypothesis tested in this study is that
      patients older than 60 years who undergo laparoscopic Roux-en-Y gastric bypass
      experience a medical benefit not significantly different from that experienced by
      younger patients in terms of the number of medications and comorbid conditions.
      METHODS: The number of preoperative and postoperative comorbid conditions and the
      medications required for those conditions were compared between consecutive
      patients older than 60 years and those younger than 60 years who underwent Roux
      en-Y laparoscopic gastric bypass. Early operative outcomes were also assessed.
      RESULTS: Analysis of 110 patients younger than 60 years compared with 20 patients
      older than 60 years revealed no difference in complication rate or length of
      hospital stay. Younger patients lost more weight and had a significantly greater
      reduction in body mass index. Younger patients also demonstrated more complete
      resolution of comorbid conditions, although this difference was not significant.
      Older patients, who had more comorbid conditions requiring more medication at the
      time of surgery, experienced a greater medication reduction during follow-up,
      although this was not statistically significant. CONCLUSIONS: Patients of
      advanced age can safely undergo laparoscopic Roux-en-Y gastric bypass. Younger
      patients can be expected to demonstrate greater weight loss and experience more
      complete resolution of their comorbid conditions. Older patients demonstrated
      greater overall reduction in medication requirements. Therefore, patients older
      than 60 years can be considered good candidates for obesity surgery and can be
      expected to enjoy substantial health benefits similar to those experienced by
      younger patients.

PMID- 15723999
TI  - Serum and peritoneal inflammatory mediators in children with suspected acute
      appendicitis.
AB  - HYPOTHESIS: Inflammatory markers differ between subjects with appendicitis and
      controls. Markers of inflammation differ in serum compared with intraperitoneal
      fluid. Among subjects with appendicitis, inflammatory markers differ between
      subjects with and without perforation. DESIGN: Cross-sectional. SETTING:
      Hospitalized care. PATIENTS: Twenty-four children who underwent an appendectomy.
      Group A (n = 19) consisted of patients with appendicitis and group N (n = 5) of
      patients with normal appendixes. MAIN OUTCOME MEASURES: Serum and peritoneal
      levels of interleukin (IL)8, IL-10, granulocyte colony-stimulating factor,
      interferon gamma soluble intercellular adhesion molecule-1, matrix
      metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 were measured
      by enzyme-linked immunosorbent assay. RESULTS: Age, sex, complete blood count, C
      reactive protein level, and serum cytokines did not significantly differ by
      group. Peritoneal concentrations of interleukin-8 (mean +/- SD, 1416.8 +/- 1436
      pg/mL vs 48 +/- 74.4 pg/mL, P = .001), IL-10 (mean +/- SD, 3085 +/- 5893 pg/mL vs
      84 +/- 46 pg/mL, P = .02), matrix metalloproteinase-9 (mean +/- SD, 1784 +/-
      1225.1 ng/mL vs 435 +/- 563 ng/mL, P = .03), and tissue inhibitor of
      metalloproteinases-1 (mean +/- SD, 8939.2 +/- 7312.2 ng/mL vs 602.1 +/- 345.6
      ng/mL, P<.001) were significantly different in group A compared with group N.
      When compared by perforation (n = 8 with perforation vs n = 11 without
      perforation), peritoneal granulocyte colony-stimulating factor levels were
      elevated in subjects with perforation (mean +/- SD, 4.3 +/- 14.4 pg/mL vs 62.7 +/
      79.2 pg/mL, P = .02). Although serum tissue inhibitor of metalloproteinases-1
      was not different between groups N and A, it was significantly different between
      group N and patients with a perforated appendicitis (mean +/- SD, 205.9 +/- 43.8
      ng/mL vs 3068.9 +/- 5122.4 ng/mL, P = .04). CONCLUSION: Presently, it is not
      practical to differentiate appendicitis in a pediatric population from other
      causes of abdominal pain based on the detection of systemic inflammatory response
      markers.

PMID- 15724000
TI  - Use of antimicrobial prophylaxis for major surgery: baseline results from the
      National Surgical Infection Prevention Project.
AB  - HYPOTHESIS: Surgical site infections (SSIs) are a major contributor to patient
      injury, mortality, and health care costs. Despite evidence of effectiveness of
      antimicrobials to prevent SSIs, previous studies have demonstrated inappropriate
      timing, selection, and excess duration of administration of antimicrobial
      prophylaxis. We herein describe the use of antimicrobial prophylaxis for Medicare
      patients undergoing major surgery. DESIGN: National retrospective cohort study
      with medical record review. SETTING: Two thousand nine hundred sixty-five acute
      care US hospitals. PATIENTS: A systematic random sample of 34,133 Medicare
      inpatients undergoing coronary artery bypass grafting; other open-chest cardiac
      surgery (excluding transplantation); vascular surgery, including aneurysm repair,
      thromboendarterectomy, and vein bypass operations; general abdominal colorectal
      surgery; hip and knee total joint arthroplasty (excluding revision surgery); and
      abdominal and vaginal hysterectomy from January 1 through November 30, 2001. MAIN
      OUTCOME MEASURES: The proportion of patients who had parenteral antimicrobial
      prophylaxis initiated within 1 hour before the surgical incision; the proportion
      of patients who were given a prophylactic antimicrobial agent that was consistent
      with currently published guidelines; and the proportion of patients whose
      antimicrobial prophylaxis was discontinued within 24 hours after surgery.
      RESULTS: An antimicrobial dose was administered to 55.7% (95% confidence interval
      [CI], 54.8%-56.6%) of patients within 1 hour before incision. Antimicrobial
      agents consistent with published guidelines were administered to 92.6% (95% CI,
      92.3%-92.8%) of the patients. Antimicrobial prophylaxis was discontinued within
      24 hours of surgery end time for only 40.7% (95% CI, 40.2%-41.2%) of patients.
      CONCLUSION: Substantial opportunities exist to improve the use of prophylactic
      antimicrobials for patients undergoing major surgery.

PMID- 15724001
TI  - Prognostic scoring in colorectal cancer liver metastases: development and
      validation.
AB  - HYPOTHESIS: A prognostic scoring system for colorectal cancer liver metastases
      that is derived from unselected patients referred for hepatic resection would
      improve the applicability and increase the accuracy of prognostication. DESIGN:
      Retrospective analysis of prospectively documented data; validation against an
      unrelated cohort from another institution. The median follow-up was 16.4 months
      (95% confidence interval, 15.0-17.8 months) (original cohort). SETTING: Two
      tertiary referral centers at unrelated university hospitals. PATIENTS:
      Independent prognosticators of survival were derived from 337 patients with
      colorectal cancer liver metastases referred for consideration of liver resection,
      and prognostic scores were calculated in 269 patients (79.8%) (original cohort).
      Calculation of prognostic scores was also applied to 193 patients referred and
      treated in an unrelated institution (validation cohort). MAIN OUTCOME MEASURES:
      Kaplan-Meier survival curve analysis (log-rank test) between different prognostic
      groups in the original and the validation cohorts. RESULTS: Independent
      prognosticators of survival were Dukes stage, number of metastases, and serum
      concentrations of carcinoembryonic antigen, alkaline phosphatase, and albumin.
      Significant differences were found in cumulative overall survival between
      patients assigned to good, moderate, and poor prognoses in the original and
      validation cohorts (P<.05). Liver resection improved survival in all prognostic
      groups. However, no patient with poor prognosis and only 19.7% (13 of 66) of
      patients with moderate prognosis survived 5 years, compared with 62.5% (10 of 16)
      of patients with good prognosis (P<.001). CONCLUSIONS: This prognostic scoring
      system is derived from and can be applied to patients with colorectal cancer
      liver metastases at the time of referral for consideration of surgery. Patients
      with poor prognosis have no long-term benefit from curative liver resection and
      should therefore be considered for combined multimodal treatment.

PMID- 15724002
TI  - Ten-year surgical experience with nontraumatic pericardial effusions: a
      comparison between the subxyphoid and transthoracic approaches to pericardial
      window.
AB  - HYPOTHESIS: The approach to pericardial window in patients with nontraumatic
      pericardial effusion impacts outcome. DESIGN: Retrospective review and comparison
      of all cases of pericardial window performed over 10 years. Follow-up was to
      patient death. SETTING: Three hospitals performing cardiothoracic surgery at a
      single university. PATIENTS: All patients in whom pericardial window was
      performed for nontraumatic pericardial effusion. MAIN OUTCOME MEASURES: Outcomes
      associated with the subxyphoid approach to pericardial window were compared with
      those associated with the transthoracic approach. The primary outcome was
      postsurgical recurrence of pericardial effusion. Secondary outcomes included
      operative time, intraoperative and postoperative complications, in-hospital
      mortality, hospital and intensive care unit lengths of stay, and days between
      surgery and death. RESULTS: Over 10 years, there were 342 patients with
      procedural codes for pericardial window in the medical record databases of 3
      hospitals performing cardiothoracic surgery at 1 university center. One hundred
      fifty-one patients were excluded because the operation was performed for trauma,
      postoperative tamponade, or pericardial biopsy without effusion. The results are,
      therefore, based on the remaining 191 procedures. The subxyphoid approach was
      used in 78 patients, and the transthoracic approach in 113 patients. Patients
      were well matched for age (P = .31), sex (P = .05), preoperative tamponade (P =
      .08), and comorbidities (P > .05). No differences were observed between the 2
      approaches in terms of recurrence of effusion, operative time, overall
      intraoperative or postoperative complications, and hospital or intensive care
      unit lengths of stay. In-hospital mortality was significantly greater in the
      subxyphoid group (27 of 78 vs 18 of 113 patients; P = .003). CONCLUSIONS: Over 10
      years, there were 191 pericardial windows performed for nontraumatic pericardial
      effusions. The subxyphoid and transthoracic approaches were well tolerated by
      patients, required short operative times, and resulted in similar rates of
      overall postoperative complications and intensive care unit and hospital lengths
      of stay. Recurrence rates were low with both procedures.

PMID- 15724003
TI  - Safety of immediate transverse rectus abdominis myocutaneous breast
      reconstruction for patients with locally advanced disease.
AB  - HYPOTHESIS: Immediate transverse rectus abdominis myocutaneous breast
      reconstruction combined with postoperative radiation therapy after mastectomy is
      safe and effective. DESIGN: Retrospective case series. SETTING: University-based
      teaching hospital. PATIENTS: From January 1, 1996, through December 31, 2003, 252
      patients underwent mastectomy and immediate transverse rectus abdominis
      myocutaneous flap reconstruction. Of those, 35 patients received postoperative
      radiation therapy (stage I, n = 1; II, n = 17; III, n = 15; IV, n = 2). Age range
      was 29 to 72 years (mean, 49.5 years). Follow-up was 1 to 8 years (mean, 48
      months). MAIN OUTCOME MEASURES: Flap loss, fat necrosis, flap volume loss,
      adjuvant treatment delay, and need for additional surgery. RESULTS: The rate of
      flap survival was 100%. Median operative time was 5.5 hours. Average hospital
      stay was 5.2 days. Fat necrosis occurred in 3 patients, with volume loss
      requiring additional surgery in 2 patients (6%). Postoperative adjuvant therapy
      was not significantly delayed (median interval, 32 days). With a median follow-up
      of 48 months, local recurrence was present in only 1 patient (3%), who underwent
      successful local salvage, and distant metastasis occurred in 4 patients (11%).
      CONCLUSIONS: Immediate transverse rectus abdominis myocutaneous breast
      reconstruction followed by radiation therapy is safe, with minimal morbidity and
      no significant change in tissue volume. Complications tend to be minor, not
      delaying adjuvant therapy. Immediate breast reconstruction should be considered
      after mastectomy, despite the need for postoperative radiation therapy.

PMID- 15724004
TI  - Management of complicated peptic ulcer disease.

PMID- 15724005
TI  - Image of the month. Vibrio Cellulitis.

PMID- 15724006
TI  - Carotid artery injury.

PMID- 15724007
TI  - Longer surgical durations can lead to significant staffing costs to the
      anesthesiology department and hospital.

PMID- 15724008
TI  - Biotechnology succeeds in revolutionizing medical science.

PMID- 15724009
TI  - Lupus miliaris disseminatus faciei: treatment with the 1450-nm diode laser.

PMID- 15724010
TI  - Microscopic in vivo description of cellular architecture of dermoscopic pigment
      network in nevi and melanomas.
AB  - OBJECTIVE: To characterize the microscopic aspects of the dermoscopic pigment
      network in vivo, by means of confocal scanning laser microscopy. DESIGN: Confocal
      imaging was performed on melanocytic lesions characterized by pigment network at
      dermoscopy. Some confocal architectural and cytologic features, as observed at
      the dermoepidermal junction, were morphologically described and quantified by
      means of a dedicated program. SETTING: University medical department. STUDY
      POPULATION: We studied confocal images of 15 melanomas, 15 dermoscopic atypical
      nevi, and 15 common nevi. MAIN OUTCOME MEASURES: Features referring to aspect,
      size, regularity, homogeneity, and infiltration of dermal papillae and to
      cellular size, regularity, and atypia were described by 2 observers on confocal
      images. Mean dermal papillary diameter, mean cell area, and shape irregularity
      were quantified by drawing papillae and cell contours on confocal images and
      measured with the use of a computer program. RESULTS: Pigment network in
      melanomas consisted of large basal cells that circumscribed small to medium-sized
      dermal papillae with marked cellular atypia, sometimes infiltrating dermal
      papillae. On the other hand, common acquired nevi were characterized by lack of
      atypical cells and edged dermal papillae. Atypical nevi presented intermediate
      characteristics between clearly benign and malignant lesions. CONCLUSION:
      Cellular atypia was the most sensitive feature for melanoma diagnosis, whereas
      the presence of nucleated cells infiltrating dermal papillae was the most
      specific one.

PMID- 15724011
TI  - Limitations of dermoscopy in the recognition of melanoma.
AB  - OBJECTIVE: To compare dermoscopic features of melanocytic nevi with those of
      early melanomas that were not excised initially because of their uncharacteristic
      clinical and dermoscopic appearance. DESIGN: Retrospective study of the baseline
      images of 325 melanocytic skin lesions that were observed by digital dermoscopy
      and finally excised because of changes over time. SETTING: A dermatologic clinic
      and a dermatologic department at a university hospital. MAIN OUTCOME MEASURES:
      Comparison of baseline images of melanomas and melanocytic nevi by pattern
      analysis, the ABCD rule of dermoscopy, and the 7-point checklist. RESULTS:
      Baseline dermoscopic images of 262 melanocytic nevi and 63 melanomas from 315
      patients were included in the analysis. The patterns of dermoscopic features
      observed in the baseline images of melanocytic lesions finally diagnosed as
      melanomas during follow-up did not differ substantially from the patterns
      observed in the baseline images of melanocytic nevi. Pattern analysis, the ABCD
      rule of dermoscopy, and the 7-point checklist failed to achieve adequate
      diagnostic accuracy for melanoma. In retrospect, no dermoscopic feature or
      pattern of features could be identified that reliably differentiated between
      melanomas and melanocytic nevi at the time of the first presentation. CONCLUSION:
      Dermoscopy depends on the appearance of classic dermoscopic features and is
      therefore limited in the diagnosis of very early and mainly featureless
      melanomas.

PMID- 15724012
TI  - Signaling networks in cutaneous melanoma metastasis identified by complementary
      DNA microarrays.
AB  - BACKGROUND: Melanoma is a complex multigenic disease, susceptibility to which is
      determined by several parallel and stepwise progressive pathways affecting growth
      control, differentiation, cell adhesion, and survival. Melanoma and human cancers
      in general undergo a continuous development from benign to malignant states, as
      most thoroughly documented in the multistep mole-to-melanoma transition.
      OBJECTIVE: To examine how high-throughput microarrays are being used in
      expression profiling to identify regulated genes, patterns, and pathways that may
      lead to functional characterization and tumor subclassification. DESIGN: Ten
      melanoma metastases were analyzed by DNA array technology for important regulated
      candidate genes, with subsequent confirmation by real-time reverse transcription
      polymerase chain reaction. RESULTS: Hepatocyte growth factor receptor c-met,
      growth factor receptor-bound protein 10, B-raf proto-oncogene, and several
      mitogen-activated protein kinase kinase genes were significantly up-regulated in
      melanoma metastases and several melanoma cell lines relative to normal human
      melanocytes (P = .03). Among the up-regulated genes, phosphorylated growth factor
      receptor-bound protein 10 is known to serve a molecular switch turning on the
      mitogen-activated protein kinase pathway in response to hepatocyte growth factor
      receptor binding. CONCLUSIONS: As suggested by the DNA arrays, we found the
      mitogen-activated protein kinase kinase/extracellular-regulated kinase pathway to
      be activated in most of the cutaneous melanoma metastasis specimens. These
      findings are in the context of the current microarray technology in melanoma
      research. Additional steps are needed to gain insights into the pluralistic
      signaling milieu of this malignancy as we enter the postgenomic era.

PMID- 15724013
TI  - A search for CDKN2A/p16INK4a mutations in melanocytic nevi from patients with
      melanoma and spouse controls by use of laser-captured microdissection.
AB  - OBJECTIVE: To determine the frequency at which the CDKN2A coding region is
      mutated in the atypical nevi of persons with sporadic melanoma. DESIGN: DNA
      samples, isolated by laser-captured microdissection of atypical nevi from 10
      patients with newly incident cases of sporadic melanoma and their spouses as
      matched controls, were used as templates for nested polymerase chain reaction
      amplification of CDKN2A exons 1 and 2. RESULTS: No point mutations in the coding
      region of CDKN2A were observed in any of the melanocytic nevi. CONCLUSIONS: Point
      mutations in CDKN2A are an uncommon event in the atypical nevi of persons with
      melanoma. As such, the data may support a hypothesis of melanocytic nevus
      histogenesis, in which the melanocytic nevus and malignant melanoma represent
      separate, pleiotropic pathways resulting from common stimuli, such as genomic
      damage from UV radiation.

PMID- 15724014
TI  - Ultrasonography using simple diagnostic criteria vs palpation for the detection
      of regional lymph node metastases of melanoma.
AB  - OBJECTIVES: Our aims were (1) to compare the respective ability of
      ultrasonography and palpation to detect nodal metastasis during initial staging
      and follow-up in patients having melanomas and (2) to assess, we believe for the
      first time, which ultrasound criteria should be used to define metastasis in
      cases of cutaneous or mucosal melanoma. DESIGN: Prospective single-center study.
      Nodal metastasis was confirmed by histopathologic evaluation. SETTING:
      Dermatology and radiology departments of a university hospital. PATIENTS: A total
      of 160 new consecutive patients with stage I to stage III melanoma. INTERVENTION:
      Experienced operators independently performed 391 paired palpation and
      ultrasonographic examinations. MAIN OUTCOME MEASURES: Firm enlarged nodes found
      on palpation were considered metastatic. On ultrasonographic examination,
      circular or oval hypoechoic lymph nodes lacking hyperechoic hila were considered
      metastatic (stringent criteria). Nodes with 2 or fewer of these patterns and
      other published signs of metastasis (ie, intranodal nodular hypoechoic focus and
      irregularity of the node margin) were considered suspicious. RESULTS: Over the 6
      year study period 33 patients developed nodal metastasis. For palpation and
      ultrasonography using the stringent criteria, respectively, sensitivity was 41.5%
      (95% confidence interval [95% CI], 29.6-53.5) and 76.9% (95% CI, 66.7%-87.2%)
      (P<.001) and specificity was 95.7% (95% CI, 93.5%-97.9%) and 98.4% (95% CI, 97.1%
      99.8%) (P<.05). Including ultrasonographically suspicious lymph nodes
      significantly lowered specificity (86.2% [95% CI, 82.5-89.9]) (P<.05) without
      improving sensitivity. Previous lymphadenectomy had little impact on
      ultrasonographic findings. CONCLUSION: Ultrasonography using stringent criteria
      of nodal metastasis, which are easy to identify and reliable, is superior to
      palpation for early detection of regional lymph node metastases of melanoma.

PMID- 15724015
TI  - Two frameshift mutations in the RNA-specific adenosine deaminase gene associated
      with dyschromatosis symmetrica hereditaria.
AB  - OBJECTIVE: To report and analyze the mutations of the double-stranded RNA
      specific adenosine deaminase (DSRAD) gene in 2 Chinese pedigrees with
      dyschromatosis symmetrica hereditaria (DSH). DESIGN: Pedigree study. SETTING:
      Anhui province of China. PATIENTS: Two Chinese families, consisting of 19
      individuals (family 1) and 5 individuals (family 2). INTERVENTIONS: We directly
      performed mutation detection of the DSRAD gene in 2 Chinese families with DSH by
      sequencing. The whole coding region of DSRAD was amplified by polymerase chain
      reaction, and products were analyzed by direct sequencing. MAIN OUTCOME MEASURES:
      Frameshift DSRAD gene mutations. RESULTS: The c.3513insC (Arg1171fs) mutation was
      found in all patients but not in the healthy individuals from family 1, and the
      c.3220_3224delGCATC (Gly1073fs) mutation was found in 2 patients but not in the
      healthy members of family 2. These 2 mutations were not found in 96 unrelated
      control individuals. CONCLUSION: Our data suggest that these 2 novel frameshift
      mutations in the DSRAD gene could cause DSH in the Chinese Han population and add
      new variants to the repertoire of DSRAD mutations in DSH.

PMID- 15724016
TI  - Clinical features of multiple cutaneous and uterine leiomyomatosis: an
      underdiagnosed tumor syndrome.
AB  - OBJECTIVE: To investigate the clinical features of the multiple cutaneous and
      uterine leiomyomatosis (MCUL) syndrome, including the hereditary leiomyomatosis
      and renal cell cancer syndrome. DESIGN: A case series of patients with multiple
      skin leiomyomas solicited via a circular letter to dermatologists. SETTING:
      Research institute. PATIENTS: A total of 108 affected individuals, including 46
      probands and 62 affected relatives. MAIN OUTCOME MEASURES: The proportion of
      probands with underlying fumarate hydratase (FH) mutations, the penetrance of FH
      mutations, and clinicopathologic features of MCUL. RESULTS: Forty-one (89%) of 46
      probands with multiple skin leiomyomas had evidence of germline FH mutations,
      which were highly penetrant. All 26 male mutation carriers had skin leiomyomas.
      Of 67 women with FH mutations, 46 (69%) had both skin and uterine leiomyomas; 10
      (15%) had only skin leiomyomas; 5 (7%) had only uterine leiomyomas; and 6 (9%)
      were clinically unaffected. Patients presented with skin leiomyomas at a mean age
      of 24 years and had a mean of 25 lesions. Forty-one individuals (89%) reported
      painful lesions, particularly in response to cold or trauma. Fibroids were
      histologically unremarkable, highly symptomatic, and associated with a high risk
      of early hysterectomy. One individual had a very aggressive collecting duct renal
      cancer. The G354R FH mutation predisposed patients to uterine fibroids without
      skin leiomyomas (P = .03). Many patients with skin leiomyomas had not previously
      presented for medical attention. Fibroids were rarely recognized as cases of
      MCUL. CONCLUSIONS: Highly penetrant FH mutations underlie MCUL. Increased
      clinical awareness is important because of the associated risk of severe uterine
      fibroids and, in some cases, aggressive renal cancer.

PMID- 15724017
TI  - Limitations of histopathologic analysis in the recognition of melanoma: a plea
      for a combined diagnostic approach of histopathologic and dermoscopic evaluation.

PMID- 15724018
TI  - Confocal scanning laser reflectance microscopy: why bother?

PMID- 15724019
TI  - Ultrasound scanning in dermatology.
AB  - In recent years, ultrasound scanning has become an important diagnostic tool in
      dermatology. It is easy to use, completely safe, and provides important
      diagnostic information. There are 2 basic types of ultrasonography with
      dermatologic applications. The best established is 20-MHz scanning, which can be
      used to measure tumor thickness and/or skin thickness when treating inflammatory
      diseases such as scleroderma or psoriasis. Real-time sonography with 7.5- to 10
      MHz probes has assumed an increasingly important role, since it is used to search
      for and image lymph nodes and subcutaneous tumors in a variety of clinical
      settings, including preoperative staging and follow-up of melanoma.
      Ultrasonography is capable of revealing the 3-dimensional size and outline of
      subcutaneous lesions, for example, lymph nodes, subcutaneous tumor masses or
      hematomas, and their relation to adjacent vessels. Moreover, information about
      the lesion quality (solid, cystic, and combined) and the inner structure
      (homogeneous, inhomogeneous, hypoechoic, hyperechoic, calcification foci, and
      necroses) can be obtained. All this information can be combined to help
      distinguish between benign and malignant lymphadenopathy and to determine the
      malignant potential of a subcutaneous lesion. In addition to conventional B-mode
      sonography, newer ultrasound techniques such as native and signal-enhanced color
      Doppler sonography can be used to assess peripheral lymph nodes.

PMID- 15724020
TI  - Molecular diagnosis of cutaneous diseases.
AB  - OBJECTIVES: To provide an update on the molecular procedures used increasingly in
      the study and diagnosis of a variety of dermatologic malignancies and
      inflammatory disorders and to explore the potential use of these techniques in
      clinical dermatology. Herein, we review assays such as G-banding, fluorescence in
      situ hybridization, comparative genomic hybridization, and spectral karyotyping
      in conjunction with the polymerase chain reaction and DNA microarrays. DATA
      SOURCES: PubMed was searched for published articles on molecular diagnosis and
      dermatologic diseases. STUDY SELECTION: All English-language studies were
      selected if they provided useful methodologic information or highlighted the
      usefulness of molecular techniques. DATA EXTRACTION: Only methodologic and
      qualitative information was extracted. DATA SYNTHESIS: The information was
      synthesized into 2 sections: one describing the principles of different molecular
      diagnostic techniques, and the other highlighting the contributions of molecular
      diagnostic techniques to the understanding and diagnosis of several dermatologic
      diseases. CONCLUSIONS: A basic understanding of the principles of molecular
      diagnostic techniques is crucial for the practicing dermatologist to benefit from
      the increasing number of molecular diagnostic articles appearing in the
      literature and potentially to apply these methods in clinical practice.

PMID- 15724021
TI  - The pyrin family of fever genes: unmasking genetic determinants of
      autoinflammatory disease.

PMID- 15724022
TI  - Neonatal-onset multisystem inflammatory disorder: the emerging role of pyrin
      genes in autoinflammatory diseases.
AB  - Neonatal-onset multisystem inflammatory disorder (NOMID) is a rare congenital
      disorder characterized by a neonatal-onset urticarial rash, arthropathy,
      recurrent fevers, and central nervous system disease. We report 3 cases in which
      patients presented with neonatal-onset urticarial eruption and other organ
      involvement of varying severity. Genetic testing of 2 of these patients revealed
      previously unreported genetic mutations in exon 3 of the CIAS1 gene, a recently
      discovered member of the pyrin gene family. The third patient did not demonstrate
      a CIAS1 mutation. These cases illustrate the genetic basis of NOMID, an
      autoinflammatory disorder, and highlight the emerging role of the pyrin gene
      family in the regulation of nuclear factor kappaB signaling and other pathways
      involved in inflammation and apoptosis.

PMID- 15724023
TI  - Telemedical wound care using a new generation of mobile telephones: a feasibility
      study.
AB  - BACKGROUND: Leg ulcers are an important cost factor in health care systems. It
      has been shown that a telemedical wound care consultation can improve quality of
      care and help reduce costs. In this study, we evaluated the feasibility of
      telemedical wound care using a new generation of mobile telephones with
      integrated cameras. OBSERVATIONS: Three physicians separately evaluated 61 leg
      ulcers for the following 9 variables: epithelialization, fibrin, necrosis, and
      granulation tissue at the center and normal border, erythema, cyanosis, eczema,
      and hyperpigmentation at the periphery. One physician performed the face-to-face
      consultation (gold standard), and 2 others performed the remote evaluation. The
      image was obtained with the mobile telephone and immediately sent via e-mail. To
      measure the agreement of the evaluation among the 3 physicians, we used Cohen
      kappa statistics. Overall, the agreement between the remote and face-to-face
      evaluations was very good, with kappa values of up to 0.94 The image quality was
      judged to be good in 36 cases (59%) and very good in 12 (20%). The participants
      felt comfortable making a diagnosis based on the pictures in 50 cases (82%).
      CONCLUSION: Although this study was performed with the first generation of these
      devices, we were able to demonstrate the feasibility of such a telemedical wound
      care consultation.

PMID- 15724024
TI  - gli-1 Oncogene is highly expressed in granulomatous skin disorders, including
      sarcoidosis, granuloma annulare, and necrobiosis lipoidica diabeticorum.
AB  - BACKGROUND: Sarcoidosis, which occurs most commonly in African American women, is
      a granulomatous multisystem disorder affecting the skin, lungs, and central
      nervous system. In a previous immunohistochemistry study of keloids, a scar
      granuloma stained highly positive for glioma-associated oncogene homologue (gli)
      1. OBSERVATION: This observation led us to study whether gli-1, one of the
      vertebrate zinc finger transcription factor genes of the gli superfamily, is
      expressed in granulomatous skin disorders such as cutaneous sarcoidosis,
      granuloma annulare (GA), and necrobiosis lipoidica diabeticorum (NLD).
      Immunohistochemistry studies for gli-1 were performed on biopsy specimens from
      patients with cutaneous sarcoidosis, GA, and NLD. All sarcoid lesions were highly
      positive for gli-1 expression, and 75% of the cells demonstrated positivity with
      a stain intensity of 3 on a scale of 1 to 3. The gli-1 expression was confined to
      cutaneous granulomas. CD68 staining was highly positive in the sarcoid lesions as
      well. Similarly, GA and NLD lesions were uniformly positive for gli-1 expression.
      CONCLUSIONS: We found that gli-1 is inappropriately expressed in granulomatous
      lesions of the skin such as cutaneous sarcoidosis, GA, and NLD. These findings
      provide a rationale for clinical trials of inhibitors of gli-1 signaling,
      including tacrolimus and sizolimus, for the treatment of cutaneous sarcoidosis
      and other granulomatous disorders of the skin.

PMID- 15724025
TI  - Crusted plaques in an immunocompromised host.

PMID- 15724026
TI  - Asymptomatic linear plaque on the neck.

PMID- 15724027
TI  - Multiple violaceous papules at an amputation site.

PMID- 15724028
TI  - Erythematous plaques with Fever and leukocytosis.

PMID- 15724029
TI  - Value of preoperative determination of skin tumor thickness with 20-MHz
      ultrasound.

PMID- 15724030
TI  - Congenital absence of the left sternomastoid muscle.

PMID- 15724032
TI  - Infants in a neonatal intensive care unit: parental response.
AB  - OBJECTIVE: To compare the psychosocial functioning of the parents (mother and
      father) of infants admitted to a neonatal intensive care unit (NICU) with the
      parents of infants born at term and not admitted to the NICU. DESIGN: Random
      sample of NICU parents and term non-NICU parents were assessed across a variety
      of psychiatric and psychosocial measures shortly after the birth of their infant.
      SETTING: Christchurch Women's Hospital, New Zealand. Labour ward and level III
      NICU. PARTICIPANTS: A total of 447 parents (242 mothers; 205 fathers) with an
      infant admitted to a regional NICU during a 12 month period; 189 parents (100
      mothers; 89 fathers) with infants born at term and not requiring NICU admission.
      MAIN OUTCOME MEASURES: Depression and anxiety symptoms, psychosocial functioning.
      RESULTS: Overall, levels of anxiety and depression were low in both parent
      groups. Compared with control parents, a higher percentage of NICU parents had
      clinically relevant anxiety and were more likely to have had a previous NICU
      admission and be in a lower family income bracket. Infant prematurity was
      associated with higher levels of symptomatology in both NICU mothers and fathers.
      CONCLUSIONS: Specific interventions are not needed for most parents who have an
      infant admitted to the NICU as they appear to adapt relatively successfully.
      Infant prematurity impacts negatively on the father as well as the mother.
      Consequently these parents may benefit from increased clinical attention.

PMID- 15724033
TI  - The Baby Friendly Hospital Initiative and breast feeding rates in Scotland.
AB  - OBJECTIVE: To examine the effect of the Baby Friendly Hospital Initiative on
      breast feeding rates in Scotland. DESIGN: Observational study using an annual
      survey of progress towards the WHO/UNICEF Baby Friendly Hospital Initiative and
      routinely collected breast feeding rates gathered on the Guthrie Inborn Errors
      Screening card at 7 days of postnatal age. SETTING: Scotland, UK, population 5.1
      million, with about 53 000 births a year. PARTICIPANTS: All 33 maternity units
      with over 50 births per annum and 464,246 infants born in Scotland between 1995
      and 2002. MAIN OUTCOME MEASURES: Baby Friendly status of each maternity unit at
      the time of an infant's birth: certificate of commitment, UK standard award, and
      breast feeding at 7 days postnatal age. RESULTS: Babies born in a hospital with
      the UK Baby Friendly Hospital Initiative standard award were 28% (p<0.001) more
      likely to be exclusively breast fed at 7 days of postnatal age than those born in
      other maternity units after adjustment for mother's age, deprivation, hospital
      size, and year of birth. From 1995, breast feeding rates had increased
      significantly faster in hospitals with Baby Friendly status by 2002: 11.39% (95%
      confidence interval 10.35 to 12.43) v 7.97% (95% confidence interval 7.21 to
      8.73). CONCLUSION: Being born in a hospital that held the award increased the
      chance of being breast fed. All maternity units should be encouraged to undertake
      the significant strategic and practical changes required to achieve UK Baby
      Friendly Hospital Initiative standard status.

PMID- 15724031
TI  - Vitamin A and preterm infants: what we know, what we don't know, and what we need
      to know.
AB  - Vitamin A is essential for optimal growth and development. In the developing
      world, vitamin A supplementation of the newborn infant reduces mortality. In the
      developed world, extremely preterm infants are born with low body stores of
      vitamin A and are at high risk of vitamin A deficiency. Optimal vitamin A
      supplementation for this population is not clearly defined, however, and, despite
      evidence of benefit, early vitamin A supplementation of extremely preterm infants
      is not uniformly practised in the United Kingdom. There is an urgent need for
      studies in preterm infants that include quantification of hepatic stores and
      functional assessment of vitamin A status as well as long term outcome.

PMID- 15724034
TI  - Vitamin C supplementation in very preterm infants: a randomised controlled trial.
AB  - OBJECTIVE: To determine whether regulating vitamin C (ascorbic acid: AA) intake
      to achieve higher or lower plasma concentrations was associated with improved
      clinical outcome. DESIGN: A double blind, randomised controlled trial. SETTING:
      Neonatal intensive care unit at Christchurch Women's Hospital. PATIENTS: Infants
      with birth weight <1500 g or gestation <32 weeks, admitted to the unit within 48
      hours of birth. INTERVENTION: Infants were randomised to one of three protocols
      with regard to AA supplementation for the first 28 days of life: group LL
      received low supplementation throughout; group LH received low until day 10 and
      then high: group HH received high throughout. MAIN OUTCOME MEASURES: Primary
      outcome measures were oxygen requirement at 28 days and 36 weeks postmenstrual
      age, total days supplemental oxygen, and retinopathy of prematurity. AA
      concentrations were measured at study entry (day 2), and days 10, 21, and 28.
      RESULTS: A total of 119 infants were enrolled over 24 months (mean gestation 28.4
      weeks; birth weight 1161 g). Six infants died, and these had significantly higher
      AA concentrations before randomisation than surviving infants (116 micromol/l
      (95% confidence interval 90 to 142) v 51 micromol/l (45 to 58), p<0.0001). There
      were no significant differences in primary outcomes between the groups. However,
      the proportion of surviving infants with an oxygen requirement at 36 weeks
      postmenstrual age in group HH (19%) was half that in group LL (41%) (p=0.06).
      CONCLUSIONS: In a randomised controlled trial, no significant benefits or harmful
      effects were associated with treatment allocation to higher or lower AA
      supplementation throughout the first 28 days of life.

PMID- 15724035
TI  - Neonatal bilirubin production-conjugation imbalance: effect of glucose-6
      phosphate dehydrogenase deficiency and borderline prematurity.
AB  - OBJECTIVE: To evaluate relations between production and conjugation of bilirubin
      in the pathophysiology of jaundice in glucose-6-phosophate dehydrogenase (G6PD)
      deficient neonates. METHODS: Term and borderline premature (35-37 weeks
      gestational age), healthy, male, G6PD deficient neonates were studied close to
      the beginning of the 3rd day. Blood carboxyhaemogobin corrected for inspired CO
      (COHbc; an index of bilirubin production) and serum total conjugated bilirubin
      (TCB; a reflection of bilirubin conjugation) were measured in simultaneously
      drawn blood samples by gas chromatography and reverse phase high performance
      liquid chromatography respectively. A bilirubin production-conjugation index
      comprising COHbc/TCB was determined; a high index reflects imbalance between the
      bilirubin production and conjugation processes. COHbc and TCB individually and
      the production-conjugation index were studied in relation to serum total
      bilirubin (STB) concentration. RESULTS: Fifty one G6PD deficient neonates were
      sampled at 51 (8) hours. COHbc values did not correlate with STB (r=0.22,
      p=0.15). TCB did correlate inversely with STB (r=-0.42, p=0.004), and there was a
      positive correlation between the production-conjugation index and STB (r=0.45,
      p=0.002). The production-conjugation index (median (interquartile range)) was
      higher in the premature (n=8) than term neonates (2.31 (2.12-3.08) v 1.05 (0.53
      1.81), p=0.003). This difference was the result of changes in TCB. CONCLUSIONS:
      The data show that jaundice in G6PD deficient neonates is the result of an
      imbalance between production and conjugation of bilirubin with a tendency for
      inefficient bilirubin conjugation over increased haemolysis in its pathogenesis.
      Borderline premature infants are at special risk of bilirubin production
      conjugation imbalance.

PMID- 15724036
TI  - Changes in mortality and morbidities among infants born at less than 25 weeks
      during the post-surfactant era.
AB  - OBJECTIVES: To compare mortality and death or major morbidity (DOMM) among
      infants <25 weeks estimated gestational age (EGA) born during two post-surfactant
      era time periods. STUDY DESIGN AND PATIENTS: Comparative cohort study of very low
      birthweight (501-1500 g) infants <25 weeks EGA in the NICHD Neonatal Research
      Network born during two post-surfactant era time periods (group I, 1991-1994,
      n=1408; group II, 1995-1998, n=1348). Perinatal and neonatal factors were
      compared, and group related mortality and DOMM risk were evaluated. RESULTS:
      Mortality was higher for group I (63.1% v 56.7%; p=0.0006). Antenatal steroids
      (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and
      bronchopulmonary dysplasia (p=0.0008) were more prevalent in group II. In a
      regression model that controlled for basic and delivery factors only, mortality
      risk was greater for group I than for group II (odds ratio (OR) 1.4, 95%
      confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS
      (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this
      difference. There was no difference in DOMM (86.8% v 88.4%; p=0.2), but risk was
      lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to
      0.94). CONCLUSION: Survival to discharge was more likely during the more recent
      period because of group differences in ANS, AABX, and surfactant. However, this
      treatment shift may reflect an overall more aggressive management approach. More
      consistent application of treatment has led to improving survival of <25 week EGA
      infants during the post-surfactant era, but possibly at the cost of greater risk
      of major in-hospital morbidities.

PMID- 15724037
TI  - The EPICure study: associations and antecedents of neurological and developmental
      disability at 30 months of age following extremely preterm birth.
AB  - AIMS: To describe perinatal factors associated with later morbidity among
      extremely preterm children at 30 months of age corrected for prematurity.
      POPULATION: Of 308 surviving children born at <or=25 weeks gestation in the
      United Kingdom and Ireland from March to December 1995, 283 (92%) were evaluated
      at 30 months of age corrected for prematurity. METHODS: Cerebral palsy, severe
      motor disability, and Bayley scores were used as dependent variables in
      sequential multiple regression analyses to identify factors associated with
      adverse outcomes. RESULTS: Adverse outcomes were consistently more common in
      boys. Factors related to perinatal illness, ultrasound evidence of brain injury,
      and treatment (particularly postnatal steroids) were associated with adverse
      motor outcomes (cerebral palsy, disability or Bayley psychomotor development
      index). Increasing duration of postnatal steroid treatment was associated with
      poor motor outcomes. A score was developed for severe motor disability with good
      negative predictive value. In contrast, mental development was associated with a
      broader range of factors: ethnic group, maternal educational level, the use of
      antenatal steroids, and prolonged rupture of membranes in addition to chronic
      lung disease. CONCLUSION: Male sex is a pervasive risk factor for poor outcome at
      extremely low gestations. Avoidable or effective treatment factors are
      identified, which may indicate the potential for improving outcome.

PMID- 15724038
TI  - Why is there a modifying effect of gestational age on risk factors for cerebral
      palsy?
AB  - OBJECTIVE: To investigate risk factors for cerebral palsy in relation to
      gestational age. DESIGN: Three case-control studies within a geographically
      defined cohort. SETTING: The former Oxfordshire Health Authority. PARTICIPANTS: A
      total of 235 singleton children with cerebral palsy not of postnatal origin, born
      between 1984 and 1993, identified from the Oxford Register of Early Childhood
      Impairment; 646 controls matched for gestation in three bands: <or=32 weeks; 33
      36 weeks; >or=37 weeks. RESULTS: Markers of intrapartum hypoxia and infection
      were associated with an increased risk of cerebral palsy in term and preterm
      infants. The odds ratio (OR) for hypoxia was 12.2 (95% confidence interval 1.2 to
      119) at <or=32 weeks and 146 (7.4 to 3651) at >or=37 weeks. Corresponding ORs for
      neonatal sepsis were 3.1 (1.8 to 5.4) and 10.6 (2.1 to 51.9). In contrast, pre
      eclampsia carried an increased risk of cerebral palsy at >or=37 weeks (OR 5.1
      (2.2 to 12.0)) but a decreased risk at <or=32 weeks (OR 0.4 (0.2 to 1.0)).
      However, all infants <or=32 weeks with maternal pre-eclampsia were delivered
      electively, and their risk of cerebral palsy was no lower than that of other
      electively delivered <or=32 week infants (OR 0.9 (0.3 to 2.7)). Nearly 60% of
      <or=32 week controls were delivered after spontaneous preterm labour, itself an
      abnormal event. CONCLUSION: Inflammatory processes, including pre-eclampsia, are
      important in the aetiology of cerebral palsy. The apparent reduced risk of
      cerebral palsy associated with pre-eclampsia in very preterm infants is driven by
      the characteristics of the gestation matched control group. Use of the term
      "protective" in this context should be abandoned.

PMID- 15724039
TI  - Impact of standardised feeding regimens on incidence of neonatal necrotising
      enterocolitis: a systematic review and meta-analysis of observational studies.
AB  - BACKGROUND: A significant and prolonged decline in the incidence of necrotising
      enterocolitis (NEC), nearing virtual elimination in some centres, has been
      observed consistently since implementation of a standardised feeding regimen.
      AIM: To systematically review the observational studies reporting incidence of
      NEC in preterm, low birth weight (LBW) neonates "before" and "after"
      implementation of a standardised feeding regimen. METHODS: The Cochrane Central
      Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002),
      Medline, Embase, Cinahl, and proceedings of the Pediatric Academic Societies
      (published in Pediatric Research from 1980) were searched in July and again in
      October 2003. The reference lists of identified observational studies, and
      personal files, were searched. No language restriction was applied. Key words
      were: standardised, enteral, feeding, neonates, necrotising enterocolitis.
      Authors were contacted for clarification of data. RESULTS: Six eligible studies
      (1978-2003) were identified. A significant heterogeneity was noted between the
      studies indicating the variations in the population characteristics and feeding
      practices over a period of 25 years. Meta-analysis of the six studies using a
      random effects model revealed a pooled risk ratio of 0.13 (95% confidence
      interval 0.03 to 0.50)-that is, introduction of a standardised feeding regimen
      reduced the incidence of NEC by 87%. CONCLUSION: Standardised feeding regimens
      may provide the single most important global tool to prevent/minimise NEC in
      preterm neonates. Randomised controlled trials are needed.

PMID- 15724040
TI  - Surgical strategies for necrotising enterocolitis: a survey of practice in the
      United Kingdom.
AB  - BACKGROUND: Strategies for the surgical management of necrotising enterocolitis
      are various and controversial. OBJECTIVE: To characterise variation in surgical
      management of this disease across the United Kingdom. METHODS: Postal survey of
      104 consultant paediatric surgeons with a 77% response rate. RESULTS: Duration of
      antibiotic treatment (median 10 days, range 6-14), time until the start of
      enteral feeding (median 10 days, range 4-21), and absolute indications for
      surgery all vary between surgeons. Peritoneal drainage is used by 95% of
      surgeons. Forty two percent use it in neonates of all weights, whereas 36%
      restrict its use to those <1000 g. Peritoneal drainage is used for stabilisation
      by 95% and as definitive treatment by 58%. At laparotomy, operative procedures
      include diverting jejunostomy, resection and stoma, resection with primary
      anastomosis, and "clip and drop". All procedures are used in infants of all
      weights except resection and primary anastomosis, which is used predominantly in
      larger infants (55% in <1000 g; 77% in >1000g; p=0.005). Infants may be
      considered too unwell for peritoneal drainage by 11% of surgeons compared with
      90% for laparotomy (p<0.0001). CONCLUSIONS: There is considerable variation in
      surgical strategies for necrotising enterocolitis. Peritoneal drainage is used by
      most surgeons, with controversial indications and expectations. The use of
      resection and primary anastomosis is influenced by the weight of the neonate.

PMID- 15724041
TI  - When does mother to child transmission of hepatitis C virus occur?
AB  - OBJECTIVE: To investigate when hepatitis C virus (HCV) infection from mother to
      child occurs, and evaluate possible associated factors. DESIGN: Prospective
      cohort study. PATIENTS: Fifty four HCV infected children tested within three days
      of birth and their mothers. MAIN OUTCOME MEASURES: HCV RNA polymerase chain
      reaction (PCR) results. RESULTS: Seventeen of the children (31%, 95% confidence
      interval 19% to 46%) were positive in the first 3 days of life and could be
      assumed to have acquired infection in utero. Testing PCR positive was not
      associated with sex (53% v 49% boys; p=0.77) or mode of delivery (29% elective
      caesarean section in both groups; p=0.98). Children with evidence of intrauterine
      infection were significantly more likely to be of lower birth weight and infected
      with genotype 1 (58% v 12%, p=0.01). Although a higher proportion of infants born
      to HCV/HIV co-infected women were PCR positive in the first 3 days of life, this
      difference did not reach statistical significance; excluding infants born to co
      infected women did not affect the results. Thirty seven of the children (68%)
      were negative in the first 3 days of life, 27 of whom were positive when tested
      again at 3 months, and nine were first PCR positive after 3 months (one child had
      no further tests). CONCLUSIONS: These results suggest that at least one third and
      up to a half of infected children acquired infection in utero. Although
      postpartum transmission cannot be excluded, these data suggest that it is rare.
      The role of HCV genotypes in the timing and mechanism of infection should be
      explored further.

PMID- 15724042
TI  - Anthropometry of fetal growth in rural Malawi in relation to maternal malaria and
      HIV status.
AB  - OBJECTIVE: To describe fetal growth centiles in relation to maternal malaria and
      HIV status, using cross sectional measurements at birth. DESIGN: A cross
      sectional study of pregnant women and their babies. Data on maternal
      socioeconomic status and current pregnancy, including HIV status and newborn
      anthropometry, were collected. Malaria parasitaemia was assessed in maternal
      peripheral and placental blood, fetal haemoglobin was measured in cord blood, and
      maternal HIV status was determined. SETTING: Two district hospitals in rural
      southern Malawi, between March 1993 and July 1994. OUTCOME VARIABLES: Newborn
      weight, length, Rohrer's ponderal index. RESULTS: Maternal HIV (adjusted odds
      ratio (AOR) 1.76 (95% confidence interval 1.04 to 2.98)) and first pregnancy (AOR
      1.83 (1.10 to 3.05)) were independently associated with low weight for age.
      Placental or peripheral parasitaemia at delivery (AOR 1.73 (1.02 to 2.88)) and
      primigravidae (AOR 2.13 (1.27 to 3.59)) were independently associated with low
      length for age. Maternal malaria at delivery and primiparity were associated with
      reduced newborn weight and length but not with disproportionate growth. Maternal
      HIV infection was associated only with reduced birth weight. The malaria and
      parity effect occurred throughout gestational weeks 30-40, but the HIV effect
      primarily after 38 weeks gestation. CONCLUSION: Fetal growth retardation in
      weight and length commonly occurs in this highly malarious area and is present
      from 30 weeks gestation. A maternal HIV effect on fetal weight occurred after 38
      weeks gestation.

PMID- 15724044
TI  - Cutis marmorata telangiectatica congenita.

PMID- 15724043
TI  - Fetal plasma testosterone correlates positively with cortisol.
AB  - BACKGROUND: Fetal exposure to testosterone has been implicated in programming
      childhood behaviour, but little is known about the determinants of fetal
      testosterone concentrations. AIMS: To investigate the relation between fetal
      testosterone and maternal and fetal cortisol. METHODS: Clinically indicated blood
      samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15-38),
      together with paired maternal samples, were analysed for testosterone and
      cortisol concentrations. RESULTS: Male fetuses had significantly higher
      concentrations of testosterone than females. Female but not male fetal
      concentrations rose significantly with gestational age. Fetal testosterone
      correlated positively with both fetal cortisol and maternal testosterone
      concentrations. Multiple regression showed that maternal testosterone and fetal
      cortisol were independently correlated with fetal plasma testosterone in both
      sexes. CONCLUSION: Unlike the norm in the adult, where testosterone production is
      often inhibited by cortisol, in the fetus there is a positive link between the
      two.

PMID- 15724045
TI  - Oral zinc supplementation in pregnant women and its effect on birth weight: a
      randomised controlled trial.
AB  - Pakistan lies in a zinc deficient area where oral zinc supplementation has been
      advocated for various reasons. A double blind, randomised case-control study was
      carried out on pregnant women to evaluate the effects of oral zinc
      supplementation on the weights of newborns. No significant difference was found
      in the birth weights between the cases supplemented with 20 mg elemental zinc and
      controls receiving oral placebos (p=0.57).

PMID- 15724046
TI  - Nasal potential difference increases with gestation in moderately preterm
      neonates on the first postnatal day.
AB  - At birth the mammalian airway switches from liquid secretion to absorption, an
      important mechanism in lung liquid clearance. Airway ion transport was examined
      on the first postnatal day in 38 moderately preterm infants (29-36 weeks
      gestation). The absorptive airway ion transport capacity was well developed
      regardless of respiratory condition and there was little capacity for Cl-
      secretion.

PMID- 15724047
TI  - Nucleated red blood cell count in term and preterm newborns: reference values at
      birth.
AB  - The prognostic value of nucleated red blood cell count at birth in relation to
      neonatal outcome has been established. However, reference values were needed to
      usefully interpret this variable. The normal range of reference values for
      absolute nucleated red blood cell count in 695 preterm and term newborns is
      reported.

PMID- 15724048
TI  - Resource use and health outcomes of paediatric extracorporeal membrane
      oxygenation.
AB  - The use of extracorporeal membrane oxygenation can be rationalised by the
      assumption that non-zero survival after refractory cardiorespiratory failure
      represents improved outcome. Survivors may have cognitive and or functional
      morbidities, require complex ongoing care, and as a consequence consume
      considerable healthcare resources.

PMID- 15724049
TI  - Pulmonary tuberculosis and extreme prematurity.
AB  - A mother, newly found to be positive for HIV, delivered her first baby at 25
      weeks gestation. The infant initially did well in spite of a symptomatic patent
      duct and a severe intraventricular haemorrhage, but became severely unwell
      needing further respiratory support on day 18. Acid fast bacilli were found in
      endotracheal secretions. After the baby's death, the bacilli were confirmed to be
      Mycobacterium tuberculosis, and the same organism was grown from the mother's
      urine. The case raised challenging issues in relatively uncharted territory in
      terms of treatment of the infant, public health issues, ethical decision making,
      and media management.

PMID- 15724055
TI  - Dr Alfred Velpeau (1795-1867) of Tours: the umbilical cord and birth asphyxia.
AB  - The son of a village farrier near Tours, Velpeau rose from humble beginnings to
      become by dint of intelligence, hard work, and determination the leading surgeon
      of his day in Paris. As professor of clinical surgery in the university he was an
      admired and respected teacher. His writings covered most aspects of medicine,
      surgery, and obstetrics.

PMID- 15724056
TI  - Use of conjugate pneumococcal vaccine by United Kingdom neonatal intensive care
      units.

PMID- 15724057
TI  - Neonatal buccal cell collection for DNA analysis.

PMID- 15724058
TI  - Neonatal resuscitation and assessment of cardiovascular status.

PMID- 15724059
TI  - Infants in a neonatal intensive care unit: parental response.

PMID- 15724060
TI  - The intensive care of infants with hypoplastic left heart syndrome.
AB  - Until a little over two decades ago, hypoplastic left heart syndrome was
      considered an inoperable and fatal condition, with most deaths occurring in early
      infancy, and almost all of those affected dying before their first birthday.
      However, the advent of surgical palliation and advances in peri-operative care,
      have offered hope to these patients and their families.

PMID- 15724061
TI  - CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent
      of CTLA-4.
AB  - Cytotoxic T lymphocyte antigen-4 (CTLA-4) is constitutively expressed on
      CD25(+)CD4(+) regulatory T cells (Treg) and is suggested to play a role in Treg
      mediated suppression. However, the results of analysis with anti-CTLA-4 have been
      controversial. We addressed this issue by analyzing mice over-expressing or
      deficient in CTLA-4. For over-expression, CTLA-4 transgenic mice expressing a
      full-length (FL) or a truncated (TL) mutant of CTLA-4 were analyzed. FL T cells
      expressed similar levels of CTLA-4 to Treg, whereas TL T cells expressed much
      higher levels on the cell surface. The number of Treg in both mice was decreased,
      although Foxp3 expression was not altered. Treg from both mice exerted
      suppressive activity, whereas CD25(-) T cells from FL mice showed no suppression.
      Furthermore, CD25(+)CD4 thymocytes from young CTLA-4-deficient mice were analyzed
      and found to exhibit suppressive activity. These results indicate that Treg exert
      in vitro suppressive activity independent of CTLA-4 expression.

PMID- 15724062
TI  - CD27(+) (memory) B cell decrease and apoptosis-resistant CD27(-) (naive) B cell
      increase in aged humans: implications for age-related peripheral B cell
      developmental disturbances.
AB  - To investigate age-related alterations in human humoral immunity, we analyzed the
      quantity and quality of peripheral B cell subsets, CD27-negative (CD27(-)) and
      CD27-positive (CD27(+)) B cells, by flow cytometry analysis in 54 aged
      individuals (mean age +/- SE, 74.6 +/- 0.7 years) and 30 young individuals (mean
      age +/- SE, 26.1 +/- 0.5 years). CD27(-) and CD27(+) B cells are regarded as
      naive and memory B cells, respectively. CD38, Ki-67, CD95 and bcl-2 were used as
      activation, proliferation and apoptotic markers. Susceptibility to apoptosis was
      evaluated by cell size and annexin-V binding in culture cells. The percentage of
      CD27(+) B cells was significantly lower in aged (mean, 19.2%) individuals than
      that in young individuals (mean, 28.2%). The opposite was true for CD27(-) B
      cells (mean, 80.8% in aged and 71.8% in young) (P < 0.01). The absolute number of
      CD27(+) B cells in aged individuals was significantly less than the number of
      CD27(-) B cells. The CD27(+) B cells from aged individuals showed little
      susceptibility to apoptosis, although CD95 expression on the CD27(+) B cells was
      significantly higher in the aged individuals than in the young individuals (P <
      0.05). The CD38 and bcl-2 expression on the CD27(-) B cells was significantly
      higher in the aged individuals than in the young individuals (P < 0.05). In
      addition, the CD27(-) B cells from the aged individuals showed a decreased
      susceptibility to apoptosis compared with that of the young individuals. These
      findings suggested that human aging leads to both quantitative and qualitative
      alterations in the peripheral B cell developmental system, including memory and
      naive B cell balance and their surface phenotypes.

PMID- 15724063
TI  - B cells play a regulatory role in mice infected with the L3 of Brugia pahangi.
AB  - Mice infected with the L3 of the filarial nematode Brugia pahangi make a strong
      T(h)2 response characterized by elevated levels of antigen-specific IL-4, IL-5
      and IL-10. Here we show that B cells from these animals are the major
      proliferating population in vitro with depletion of B cells or infection of muMT
      mice, resulting in reduced levels of antigen-specific proliferation. B cells also
      act as antigen-presenting cells (APC) to CD4(+) cells as demonstrated by the
      switch in cytokine profiles upon B cell depletion. The efficiency of B cells in
      antigen presentation is attenuated by IL-10 which down-regulates the expression
      of B7-1 and B7-2 on the surface of B cells both in vitro and in vivo. Thus, IL-10
      may modulate CD4 responses in L3-infected mice by suppressing the expression of
      B7 ligands on B cells. In support of this hypothesis, blockade of the IL-10R in
      vivo results in increased proliferation of CD4(+) cells. We propose that B cells
      participate in a negative feedback loop: IL-10 elicited by infection with L3 and
      produced by B cells (and CD4(+) cells) down-regulates the expression of B7
      molecules on the B cell surface, attenuating their efficiency as APC to CD4(+) T
      cells and restricting their expansion.

PMID- 15724064
TI  - Peptide analogues of a T-cell epitope of ricin toxin A-chain prevent agonist
      mediated human T-cell response.
AB  - The clinical efficacy of immunotoxins (IT) containing ricin toxin A-chain (RTA)
      can be drastically reduced by anti-toxin-neutralizing antibodies developed by
      patients. Strategies aimed at epitope-specific modulation of the immune response
      must be therefore set up to broaden the clinical applicability of RTA-based IT.
      Prevention or reduction of humoral immune responses against RTA could be achieved
      by peptide-based down-modulating strategies. Peptide analogues were investigated
      as candidate antagonist altered peptide ligands (APL) considering the sequence of
      a previously identified dominant T-cell epitope of RTA (i.e. I175-E185) presented
      in the context of the HLA-DRB1*03011 allele. Alanine-substituted peptides
      provided information on the role of individual residues of the wild-type peptide
      and allowed to identify one antagonist APL corresponding to the double-mutant
      peptide E177A/A178D. The analogue E177A/A178D not only prevented the agonist from
      stimulating anti-RTA human T-cell clones but also failed to induce down
      regulation of surface-expressed TCR, thus suggesting its possible use for in vivo
      immune modulation of anti-RTA responses.

PMID- 15724066
TI  - The structure of short-lived excited states of molecular complexes by time
      resolved X-ray diffraction.
AB  - Experimental and computational methods for time-resolved (TR) diffraction now
      allow the determination of geometry changes on molecular excitation. The first
      results indicate significant changes in the interatomic distances and molecular
      shape on photo-excitation, but also a dependence of the induced changes on the
      molecular environment. Though the use of high-brightness synchrotron sources is
      essential, it limits the time resolution to the width of the synchrotron pulse
      which is currently 70-100 ps. The experiments discussed fall into two categories:
      (i) picosecond powder diffraction experiments on the molecular excitation to a
      singlet state, and (ii) microsecond experiments on the excited states of
      inorganic complexes. Both involve reversible processes for which a stroboscopic
      technique can be applied.

PMID- 15724067
TI  - Clifford algebra approach to the coincidence problem for planar lattices.
AB  - The problem of coincidences of planar lattices is analyzed using Clifford
      algebra. It is shown that an arbitrary coincidence isometry can be decomposed as
      a product of coincidence reflections and this allows planar coincidence lattices
      to be characterized algebraically. The cases of square, rectangular and rhombic
      lattices are worked out in detail. One of the aims of this work is to show the
      potential usefulness of Clifford algebra in crystallography. The power of
      Clifford algebra for expressing geometric ideas is exploited here and the
      procedure presented can be generalized to higher dimensions.

PMID- 15724068
TI  - Generalized quasiperiodic patterns and superstructures in quasicrystals.
AB  - Patterns with octagonal and icosahedral symmetries obtained from periodic two
      dimensional (2D) 8-grids and three-dimensional (3D) 12-grids by the dual method
      are shown to be superstructures of the Beenker pattern and the 3D Penrose pattern
      with the same edge length. The superstructures are described in the same spaces
      as those of the latter (4D for the Beenker and 6D for the 3D Penrose patterns) in
      the section method but their lattice constants are doubled. The occupation
      domains and the diffraction patterns for these cases are given.

PMID- 15724069
TI  - Reconstruction of complex single-particle images using charge-flipping algorithm.
AB  - An iterative algorithm is developed to retrieve the complex exit-face
      wavefunction for a two-dimensional projection of a nanoparticle from a
      measurement of the oversampled modulus of its Fourier transform in reciprocal
      space. The algorithm does not require the support (boundary) of the object to be
      known. A loose support for the complex object is gradually found using the
      Oszlanyi-Suto charge-flipping algorithm, and a compact support is then
      iteratively developed using a dynamic Gerchberg-Saxton-Fienup algorithm. At the
      same time, the complex object is reconstructed using this compact support. The
      algorithm applies to the reconstruction of complex images with any distribution
      of phase values from 0 to 2pi. Modification of the algorithm by using real-value
      constraints for a complex object in the charge-flipping algorithm leads to faster
      reconstruction of the object whose phase value is smaller than pi/2.

PMID- 15724070
TI  - On the algebra of binary codes representing close-packed stacking sequences.
AB  - A systematic use of binary codes derived from the Hagg symbol are used to study
      close-packed polytypes. Seitz operators acting over the corresponding binary
      codes are defined and used. The number of non-equivalent polytypes of a given
      length are calculated through the use of the Seitz operators. The same procedure
      is applied to the problem of counting the number of polytypes complying with a
      given symmetry group. All counting problems are reduced to an eigenvector problem
      in the binary code space. The symmetry of the binary codes leads to the different
      space groups to which polytypes can belong.

PMID- 15724071
TI  - The Ewald dynamical diffraction theory--ninety years later.
AB  - Diffraction on a crystalline slab formed by point-like scattering centres is
      treated as a multiple scattering problem based on the Ewald equations. Using
      general results expressed in a lucid matrix form, the two-beam solution for both
      coplanar and non-coplanar cases valid near and far from Bragg peaks is found and
      a detailed comparison of the final formulae obtained with those following from
      Laue's theory is performed.

PMID- 15724072
TI  - A study of charge density in copper.
AB  - Quantitative convergent-beam electron diffraction (QCBED) experiments allow
      absolute scale measurements of low-order structure factors with very high
      accuracy. In this paper, eight low-order structure factors for copper measured by
      QCBED have been combined with the higher-order gamma-ray structure factors in
      order to obtain a larger highly accurate experimental data set. The gamma-ray
      values were relativistically corrected and rescaled. The new data set was then
      used for studying the charge distribution in copper. Charge deformation maps have
      been produced and both a maximum-entropy and a multipole analysis have been
      applied to the data. The result is compared to density functional theory
      calculations. An almost spherical charge depletion is found around the atomic
      sites showing typical metal bonding in copper.

PMID- 15724073
TI  - Solving non-centrosymmetric two-dimensional crystal structures by dynamic
      electron diffraction.
AB  - Despite the fast increase in expertise developed in the field of electron
      crystallography, dynamic scattering effects still remain a severe obstacle in
      this field, a hurdle that is being circumvented rather than fully tackled. In
      this paper, a new way of straightforward interpretation of conventional many-beam
      zone-axis dynamical electron diffraction patterns is presented that helps to
      solve the phase problem for non-centrosymmetric two-dimensional crystal
      structures, in particular if these contain only a few heavier atoms. While the
      implementation of this method is easiest for fairly weak multiple scattering, its
      extension to arbitrarily strong dynamical effects is mentioned. A method to
      obtain high-resolution diffraction data in the presence of specimen bending is
      proposed.

PMID- 15724074
TI  - Diffraction and imaging from a beam of laser-aligned proteins: resolution limits.
AB  - The effect of the limited alignment of hydrated molecules is considered in a
      laser-aligned molecular beam, on diffraction patterns taken from the beam.
      Simulated patterns for a protein beam are inverted using the Fienup-Gerchberg
      Saxton phasing algorithm, and the effect of limited alignment on the resolution
      of the resulting potential maps is studied. For a typical protein molecule
      (lysozyme) with anisotropic polarizability, it is found that up to 1 kW of
      continuous-wave near-infrared laser power (depending on dielectric constant),
      together with cooling to liquid-nitrogen temperatures, may be needed to produce
      sufficiently accurate alignment for direct observation of the secondary structure
      of proteins in the reconstructed potential or charge-density map. For a typical
      virus (TMV), a 50 W continuous-wave laser is adequate for subnanometre resolution
      at room temperature. The dependence of resolution on laser power, temperature,
      molecular size, shape and dielectric constant is analyzed.

PMID- 15724075
TI  - Intensity of N-beam X-ray diffraction: kinematical theory for a small crystal.
AB  - For a small and ideally imperfect crystal, a method for calculating n-beam X-ray
      diffraction intensities has been developed on the basis of macroscopic intensity
      exchanges among the beams. This kinematical formulation results in a set of
      simultaneous equations that can be solved by numerical calculation. To validate
      the macroscopic formulae, the Darwin intensity transfer equations, which describe
      microscopic interactions by both diffraction and absorption, are integrated on a
      spherical crystal. With the hypotheses that one beam contributes to other beams
      as proportional to its observed intensity, the macroscopic and microscopic
      formulations are proved to be equivalent; quantitative evaluation of the n-beam
      effect thereby becomes available for practical experiments using a specimen with
      finite cross section of X-ray absorption. Examples of the psi-scan simulation on
      Si 111 and 222 are presented to characterize the present method, demonstrating
      the reasonable behaviour of the observed diffraction intensity while the linear
      absorption coefficient and the specimen size are varied.

PMID- 15724076
TI  - Quantitative structure retrieval at atomic resolution.
AB  - The ability to determine the structure of a sample at atomic resolution is
      crucial for the development of nanotechnology and materials science.
      Consequently, structure retrieval must become a quantitative rather than a
      qualitative exercise. A method to retrieve the projected potential of a
      crystalline sample by inversion from an exit-surface wavefunction in high
      resolution electron microscopy is proposed. This method accounts for both
      multiple scattering and absorption.

PMID- 15724078
TI  - Ewald Prize awarded to Professor Philip Coppens.

PMID- 15724079
TI  - Insulin-like growth factor-I stimulated DNA replication in mouse endometrial
      stromal cells.
AB  - Much evidence has suggested that sex steroid hormone-induced growth of uterine
      cells is mediated by polypeptide growth factors synthesized in uterine tissues.
      The present study aimed to clarify the effect of insulin-like growth factor-I
      (IGF-I) on the proliferation of mouse endometrial stromal cells obtained from
      immature mice. IGF-I and IGF-I receptor (type I) mRNAs were detected in the
      endometrial stromal cells. IGF-I increased bromodeoxyuridine (BrdU) uptake in the
      endometrial stromal cells, indicating an increase in DNA replication. E2
      increased IGF-I mRNA levels in the endometrial stromal cells. IGF-I receptor is a
      tyrosine kinase receptor, and treatment with genistein, a tyrosine kinase
      inhibitor, reduced IGF-I-induced BrdU-uptake in the endometrial stromal cells.
      IGF-I signaling pathways involve mitogen-activated protein (MAP) kinase and
      phosphatidylinositol-3 kinase (PI-3 kinase). Treatment with 10(-7) M of the MAP
      kinase inhibitor PD098059 and 10(-5) M of the PI-3 kinase inhibitor LY294002
      decreased IGF-I-induced BrdU-uptake in the endometrial stromal cells. However,
      LY294002 (10(-5) M) also decreased the BrdU-uptake in the absence of IGF-I
      treatment. These results suggest that endometrial IGF-I is involved in the
      proliferation of endometrial stromal cells in a paracrine or autocrine manner,
      and that the MAP kinase pathway is involved in DNA replication of endometrial
      stromal cells.

PMID- 15724080
TI  - Immunolocalization of steroidogenic enzymes P450scc, 3betaHSD, P450c17, and
      P450arom in Gottingen miniature pig testes.
AB  - The objective of this study was to investigate immunolocalization of
      steroidogenic enzymes in Gottingen miniature (GM) pig testes. Testes of 6 adult
      GM pigs were obtained in September 1996 (n=2), February (n=2) and June (n=2),
      1997. Steroidogenic enzymes were immunolocalized using polyclonal antisera raised
      against bovine adrenal cholesterol side-chain cleavage cytochrome P450 (P450scc),
      human placental 3beta-hydroxysteroid dehydrogenase (3betaHSD), porcine testicular
      17alpha-hydroxylase cytochrome P450 (P450c17), and human placental aromatase
      cytochrome P450 (P450arom). Histologically, all types of spermatogenic cells
      including mature-phase spermatozoa in seminiferous tubules were observed in all
      testes throughout the year. Moreover, P450scc, 3betaHSD, P450c17and P450arom were
      identified in Leydig cells but not in Sertoli cells of all testes. These results
      suggested that adult GM pig testes have the ability to produce germ cells
      throughout the year, and the synthesis of progestin, androgen and estrogen occurs
      in the Leydig cells of GM pig testes.

PMID- 15724081
TI  - Uric acid, microalbuminuria and cardiovascular events in high-risk patients.
AB  - BACKGROUND: Elevated levels of serum uric acid and albuminuria are associated
      with cardiovascular disease, but the relationships have not consistently been
      demonstrated to be independent of hypertension, other risk factors, or each
      other. The purpose of this study was to evaluate people at high risk for
      cardiovascular disease for the influence of uric acid and microalbuminuria on
      cardiovascular events. METHODS: Consecutive consenting patients undergoing
      elective angiography (n = 316) had coronary artery disease, risk factors, renal
      function and diuretic use assessed at baseline. Cardiovascular mortality and
      major clinical events (myocardial infarction, stroke, amputation, and kidney
      failure) were ascertained over 5 years. RESULTS: Cardiovascular events occurred
      in 10% of the patients. Significant correlates (p < 0.05) of cardiovascular
      events with baseline measures included uric acid > or =5.2 mg/dl, total
      cholesterol > or =200 mg/dl, severe angiographic coronary artery disease, loop
      diuretic therapy, and diagnosis of hypertension. A stepwise Cox modeling
      procedure identified uric acid (p = 0.040), the interaction of hypertension and
      uric acid (p = 0.029), the interaction of total cholesterol and severe coronary
      artery disease (p = 0.001) and loop diuretic therapy (p = 0.009) as significant
      independent predictors of events. Although microalbuminuria was not retained in
      the final multivariate model, it was associated with poorer cardiovascular
      disease outcomes. The mean event-free survival for albumin-to-creatinine >30 mg/g
      was 51 months and for albumin-to-creatinine <30 mg/g the mean was 57 months (p =
      0.021). CONCLUSIONS: Uric acid > or =5.2 mg/dl independently imparted a 3.5-fold
      increased risk (OR 3.5, 95% CI 1.0-11.9) for cardiovascular death and major
      clinical events over a 5-year period. Uric acid may be a contributing factor to
      the progression of atherosclerosis and its complications.

PMID- 15724082
TI  - Serum uric acid independently predicts mortality in patients with significant,
      angiographically defined coronary disease.
AB  - BACKGROUND: Uric acid is a nontraditional risk factor implicated in the
      development of coronary artery disease (CAD). This study prospectively evaluated
      the predictive value of serum uric acid (SUA) levels for mortality after
      angiographic diagnosis of CAD. METHODS: Blood samples were collected from 1,595
      consecutive, consenting patients with significant, angiographically defined CAD
      (stenosis 70%). Baseline and procedural variables were recorded and levels of SUA
      were measured. Patients were followed to death or to the time of contact (mean
      2.6 years, range 1.8-5.0 years). RESULTS: Patients averaged 65 +/- 11 years of
      age, 78% were male and 170 subjects died during the follow-up period. In
      univariate analysis of prospectively defined quintiles, SUA predicted all-cause
      mortality (fifth quintile vs. first four quintiles: hazard ratio 1.9, p < 0.001).
      In multivariable Cox regression controlling for 20 covariables, independent
      predictive value for mortality was retained by SUA (hazard ratio 1.5, confidence
      interval 1.02-2.1, p = 0.04). In subgroup analysis based on diuretic use status,
      SUA independently predicted mortality among patients not using diuretics, while
      SUA was not a significant predictor of mortality among those who used diuretics.
      CONCLUSIONS: In patients with significant, angiographically defined CAD, SUA
      predicted mortality independent of traditional risk factors. This suggests that
      elevated SUA may be a risk factor for mortality in patients with significant
      cardiovascular disease and may be a stronger secondary than primary risk factor
      in CAD.

PMID- 15724083
TI  - Sketches of otohistory. Part 7: The nineteenth-century rise of laryngology.

PMID- 15724084
TI  - Combined electric and acoustic stimulation of the auditory system: results of a
      clinical study.
AB  - Combined electric and acoustic stimulation (EAS) of the auditory system is a new
      therapy for patients with severe to profound high- and mid-frequency hearing loss
      but remaining low-frequency hearing. In a prospective study, 13 patients with low
      frequency hearing of better than 60 dB below 1 kHz were implanted with a MED-EL
      COMBI 40+ cochlear implant. Pure tone thresholds as well as monosyllabic word
      scores and Hochmair-Schulz-Moser sentences in quiet and in noise were measured
      with hearing aids, cochlear implant alone and in the combined stimulation mode
      (EAS) in the same ear. Hearing could be partially preserved in 11 out of the 13
      patients. All patients scored significantly higher with cochlear implant alone
      than with hearing aids. Seven patients scored higher in the EAS mode than with
      cochlear implant alone for sentences in noise, 4 remained unchanged, and 2 could
      not use EAS. Synergistic effects of EAS were most prominent for hearing in noise
      with increases of up to 72% as compared to cochlear implant alone.

PMID- 15724085
TI  - Communication between the perilymphatic scalae and spiral ligament visualized by
      in vivo MRI.
AB  - We evaluated the transport of Gadolinium-diethylenetriaminepentaacetate
      bismethylamide (Gd-DTPA-BMA) through the round window (RW) membrane into the
      perilymphatic space with 4.7-T MRI in an animal study and 1.5-T MRI in humans.
      After administration of Gd-DTPA-BMA onto the intact RW membrane of guinea pig, Gd
      DTPA-BMA uptake was observed in the basal turn and part of the second turn within
      40 min. The scala tympani, scala vestibuli, the fibrous part of the spiral
      ligament and semicircular canal all showed uptake of Gd-DTPA-BMA. All turns of
      the cochlea were filled with Gd within 10 min in the perforated RW membrane
      administration group and within 30 min in the intravenous administration group.
      In patients who accepted middle ear injection of Gd-DTPA-BMA, uptake was observed
      within 2 h in the basal turn and semicircular canal. After 12 h the apex did
      still not show any uptake. Gd-DTPA-BMA is transported from the RW to the
      semicircular canal, the scala tympani and scala vestibuli without passing the
      helicotrema.

PMID- 15724086
TI  - Auditory and electrophysiological patterns of a unilateral lesion of the lateral
      lemniscus.
AB  - Auditory disorders resulting from focal brainstem lesions are rarely symptomatic.
      Isolated lesions of the inferior colliculus have previously been reported,
      whereas no detailed description of a localized involvement of the lateral
      lemniscus is yet available. We report a unilateral lesion of the lateral
      lemniscus by a bleeding in a cavernoma. Symptoms included strictly contralateral
      tinnitus and auditory impairment, with normal pure-tone and speech audiometry.
      Conversely, the dichotic listening test revealed an extinction of contralateral
      ear input. The brainstem auditory evoked potentials disclosed a reduced and
      delayed wave V only after contralateral ear stimulation, while the middle latency
      evoked potentials were normal. This observation shows that a unilateral lesion of
      the lateral lemniscus can produce auditory symptoms. The dysfunction of auditory
      pathways is associated with specific electrophysiological abnormalities that can
      be assessed by evoked potential recording.

PMID- 15724087
TI  - Does the bone-anchored hearing aid have a complementary effect on audiological
      and subjective outcomes in patients with unilateral conductive hearing loss?
AB  - OBJECTIVES: To study the effect of a bone-anchored hearing aid (BAHA) in patients
      with unilateral conductive hearing loss. STUDY DESIGN: Prospective evaluation on
      18 subjects. METHODS: Aided and unaided binaural hearing was assessed in the
      sound field using a sound localization test and a speech recognition in noise
      test with spatially separated sound and noise sources. The patients also filled
      out a disability-specific questionnaire. PATIENTS: 13 out of the 18 subjects had
      normal hearing on one side and acquired conductive hearing loss in the other ear.
      The remaining 5 patients had a unilateral air-bone gap and mild symmetrical
      sensorineural hearing loss. RESULTS: Sound localization with the BAHA improved
      significantly. Speech recognition in noise with spatially separated speech and
      noise sources also improved with the BAHA. Fitting a BAHA to patients with
      unilateral conductive hearing loss had a complementary effect on hearing.
      Questionnaire results showed that the BAHA was of obvious benefit in daily life.
      CONCLUSIONS: The BAHA proved to be a beneficial means to optimize binaural
      hearing in patients with severe (40-60 dB) unilateral conductive hearing loss
      according to audiometric data and patient outcome measures.

PMID- 15724088
TI  - Effects of stimulation rate on speech recognition with cochlear implants.
AB  - Phoneme and speech recognition were measured as a function of stimulation pulse
      rate in 12 listeners with three types of cochlear implants. Identification of
      consonants and vowels and recognition of words and sentences were measured in 5
      Clarion C1 subjects fit with continuous interleaved sampling (CIS) processors
      having 4 or 8 electrodes, 4 Nucleus 24 subjects fit with CIS processors having 4,
      8, 12 or 16 electrodes and 3 Clarion C2 subjects fit with CIS processors with 4,
      8, 12 and 16 electrodes. Stimulation rates ranged from 200 to more than 5000 Hz
      per electrode, depending on the device, number of electrodes used and stimulation
      strategy. Listeners were also tested on the same materials with their original
      processor prior to receiving the experimental processors. All testing was done in
      quiet listening conditions with essentially no practice with the experimental
      processor prior to data collection. Listeners scored the highest with their
      original processor. Little difference in speech understanding was observed for
      listener scores with processors using different stimulation rates. Speech
      recognition was significantly poorer only at the lowest stimulation rate and at
      high rates that used noninterleaved pulses. Speech recognition was similar for
      processors using 8, 12 or 16 electrodes. Only 4-electrode processors produced a
      significantly poorer performance. These results suggest that patients with
      present commercial implants are not able to make full use of the number of
      channels of spectral information delivered by the present speech processors. In
      addition, the results show no significant change in performance as a function of
      stimulation rate, suggesting that high stimulation rates do not result in
      improved access to temporal cues in speech, at least under quiet listening
      conditions.

PMID- 15724089
TI  - A special issue of Dermatology dedicated to Theo Rufli.

PMID- 15724090
TI  - Changes of epidermal mu-opiate receptor expression and nerve endings in chronic
      atopic dermatitis.
AB  - There is increasing evidence that neuropeptides such as a substance P,
      neurotrophins or beta-endorphin, an endogenous agonist for mu-opioid receptor,
      are involved in the pathogenesis of atopic dermatitis in which mental stress and
      scratching deteriorate the disease. mu-Opioid receptor, a G-protein-coupled
      receptor, can be downregulated and internalized by agonists and other factors in
      vitro. In this study, we investigated the regulation of mu-opioid receptor and
      nerve endings in atopic dermatitis patients. Skin biopsies from atopic dermatitis
      patients revealed a significant downregulation of mu-opiate receptor expression
      in epidermis of atopic dermatitis. Permeabilization of the skin showed that the
      receptor in keratinocytes from atopic dermatitis is internalized. The mRNA
      expression pattern of the mu-opiate receptor is different in epidermis taken from
      patients with chronic atopic dermatitis compared to normal skin. In atopic
      dermatitis, the mRNA is concentrated in the subcorneal layers of the epidermis
      and in normal skin in the suprabasal layers. Staining of the nerve endings using
      protein gene product 9.5 shows a different pattern of epidermal nerve endings in
      normal skin compared to atopic dermatitis. In normal skin, the epidermal nerve
      endings are rather thick. However, in atopic dermatitis, the epidermal nerve
      endings are thin and run straight through the epidermis. Based on these
      observations and combining the 'intensity' and 'pattern' hypothesis, we propose a
      new theory especially for histamine-unrelated, peripheral induction of chronic
      pruritus. We suggest that 'itch' is elicited in the epidermal unmyelinated nerve
      C-fibers and 'pain' in the dermal unmyelinated nerve fibers. The downregulation
      of the opioid receptor in the epidermis contributes to the chronic itching. We
      call this new hypothesis the 'layer hypothesis'.

PMID- 15724091
TI  - Rosacea: an update.
AB  - Rosacea is a common chronic cutaneous disorder of unknown etiology which occurs
      most commonly in middle-aged individuals. Cutaneous manifestations include
      transient or persistent facial erythema, telangiectasia, edema, papules and
      pustules that are usually confined to the central portion of the face. The
      National Rosacea Society's Expert Committee on the Classification and Staging of
      Rosacea identified four subtypes of rosacea: erythematotelangiectatic,
      papulopustular, phymatous and ocular. Recently, a standard grading system for
      assessing gradations of the severity of rosacea has been reported. Little is
      known about the cause of rosacea. Genetic, environmental, vascular, inflammatory
      factors and microorganisms such as Demodex folliculorum and Helicobacter pylori
      have been considered. Topical metronidazole and azelaic acid have been
      demonstrated to be effective treatments for rosacea. Severer or persistent cases
      may be treated with oral metronidazole, tetracyclines or isotretinoin.

PMID- 15724092
TI  - The role of HLA A2 and Cw2 in the pathogenesis of human demodicosis.
AB  - BACKGROUND: Demodicosis is a chronic skin disease caused by parasitic mites of
      the genus Demodex. It usually affects the face area causing major esthetical
      problems. The pathogenesis of demodicosis is not fully understood; however, it is
      quite apparent that immunological mechanisms mediate its development. OBJECTIVE:
      The goal of this study was to study the correlation between immunological and
      immunogenetic data obtained from patients with demodicosis in order to clarify
      the pathogenesis of Demodex infestation. METHODS: Twenty-five patients with
      demodicosis and 13 age- and sex-matched healthy subjects participated in the
      study. The presence of mites was determined by microscopic inspection of sebum
      gland secretions. The immune response was evaluated by identifying membrane
      markers of different immune cells using monoclonal antibodies (anti-CD3+, CD4+,
      CD8+, CD16+, CD20+ and CD95+) while the concentration of IgA, IgM and IgG was
      measured by simple radial immunodiffusion. The level of circulating immune
      complexes and total hemolytic complement as well as the preparatory and digestive
      function of neutrophils and the functional activity of leukocytes were also
      studied. Patients were typed for HLA A, B, Bw and Cw using the
      microlymphocytotoxicity method. RESULTS: The comparison between patients with and
      without the A2 phenotype showed that the latter have lower numbers of CD8+, lower
      functional activity of leukocytes, higher concentrations of IgA, larger affected
      skin areas and are more often affected by deep papular and papulopustular forms
      of demodicosis than those with the A2 phenotype, showing that this allele has a
      protective role in demodicosis. Patients exhibiting the Cw2 phenotypes were
      rather susceptible to demodicosis. They showed decreased numbers of CD3+,
      increased levels of phagocytic activity, higher mite density and severer skin
      damage as compared to patients lacking Cw2. CONCLUSIONS: The HLA A2 and Cw2
      phenotypes have an important diagnostic, prognostic and pathogenetic significance
      and could play a role in resistance or susceptibility to demodicosis by
      regulating the end phase of the immune response.

PMID- 15724093
TI  - Maggot debridement therapy in the treatment of chronic wounds in a military
      hospital setup in Turkey.
AB  - BACKGROUND: The medicinal use of maggots for the biological debridement of
      chronic wounds is increasing around the world, due to its efficacy, safety and
      simplicity. Thousands of patients have been treated in private and governmental
      hospitals during the last 10 years. OBJECTIVE: To examine the efficacy of maggot
      debridement therapy (MDT) in the debridement of chronic wounds in a military
      hospital. METHODS: MDT was applied for 1-9 days to 7 male and 4 female soldiers
      or their family members (21-72 years old) with chronic wounds. RESULTS: Complete
      debridement was achieved in 10 out of 11 patients, while in 1 patient the wound
      could be cleaned only partially. A remarkable reduction in the odor emanating
      from the wound and notable granulation were observed in all debrided wounds.
      Increased pain was observed in 1 patient with a venous stasis ulcer. CONCLUSION:
      We believe that MDT is a rapid and effective method for the debridement of
      chronic wounds in a military environment especially in times of war in developing
      countries.

PMID- 15724094
TI  - Systemic immediate allergic reactions to arthropod stings and bites.
AB  - Most of the encounters with biting and stinging insects result in more or less
      pronounced localized reactions. Typically, urticarial wheals and papular
      reactions are observed. Less often local bullous or hemorrhagic or disseminated
      papular reactions, particularly in children and immunologically naive adults, may
      be seen. With the exception of bee and wasp venom allergies, immediate-type
      allergic reactions to arthropod stings and bites are rare. Systemic IgE-mediated
      hypersensitivity has also been reported from additional hymenoptera species, e.g.
      hornets, bumble bees and ants. Rare are systemic reactions to mosquitoes, flies
      or kissing bugs and exceptional from ticks, bed bugs, moths, caterpillars and
      spiders. A major problem is the often lacking standardization of extracts for
      skin testing and for the determination of specific IgE. Some of the allergens
      have been characterized and few of them synthesized using recombinant techniques.
      Most investigations have been made with whole-body extracts or extracts from
      salivary glands, while desensitization has rarely been attempted. Currently,
      primary prevention by avoidance of stings and bites, and adequate instruction of
      sensitized individuals in the use of emergency drugs are mandatory.

PMID- 15724095
TI  - HIV dermatology in Switzerland--from the beginning to the present.
AB  - The panendemic of HIV has markedly influenced the dermatology of our generation.
      This new infection produced atypical manifestations of known dermatological
      diseases. And beyond that, mucocutaneous diseases emerged, which had not yet been
      described. Classical epidemiological studies concluded that clustering of AIDS
      cases could be explained only if AIDS was an infection transmitted by sexual
      activity or blood. Switzerland was hit early on by the HIV epidemic, and Theo
      Rufli, the leading expert on sexually transmitted diseases in our country, was
      involved from the beginning. He contributed with his team to a better delineation
      of the cutaneous manifestations of HIV infection by directing one of the largest
      prospective studies on the natural course of cutaneous manifestations of HIV. In
      addition, he participated in studies which documented new skin diseases in HIV
      infected patients. From the very beginning of the epidemic in Switzerland, Theo
      Rufli founded an organization which helped patients cope with their diagnosis. In
      Basel, an anonymous consultation facility was established. Theo Rufli also
      strongly supported the 'Stop AIDS' campaign. This review looks back on the
      history of HIV in Switzerland and especially in Basel.

PMID- 15724096
TI  - Sexually transmitted infections in Switzerland: return of the classics.
AB  - Recent trends in western Europe show an increase in sexually transmitted
      infections (STIs). Available surveillance data in Switzerland confirm this rising
      trend. Gonorrhoea rates more than doubled between 1996 and 2003, and for
      Chlamydia there was a 64% increase from 1999 to 2003. Notifications of syphilis
      cases almost doubled in the year 2002 and rose to 174% compared to the period of
      1998-2001. The resurgence of syphilis in 2002 and 2003 was most important in
      Zurich and Geneva with 54 and 24% of all cases, respectively. Eighty-four percent
      occurred in males, 40% affecting males who had sex with males, and at least 17%
      were HIV co-infected. For 2004, further increases in these bacterial STIs are
      expected. Increased awareness of the symptoms and signs of acute infections is
      needed as well as considering the diagnosis of STIs in patients with vague
      symptoms. In addition, laboratory reporting or mandatory disease notifications
      are needed to monitor syphilis trends in Switzerland.

PMID- 15724097
TI  - Vulvar dermatoses--irritant and allergic contact dermatitis of the vulva.
AB  - Irritant and allergic contact dermatitis are commonly seen in patients
      complaining about itching, burning and irritation in the vulvar area. Irritation
      often precedes allergic sensitization. Clinically, irritant and allergic contact
      dermatitis can be difficult to distinguish. Diagnosis is made by history,
      clinical investigation and patch testing. Recommended patch test series are the
      standard series, a medicament series, the patient's own topical medicaments,
      popular remedies and other suspected products. A skin biopsy may be useful to
      establish the diagnosis of contact dermatitis, but it is usually not helpful for
      the differential diagnosis between irritant and allergic dermatitis.

PMID- 15724098
TI  - Dermatoses of the male genital area.
AB  - This is an overview of dermatoses which are predominantly seen in the genital
      area. Five large groups of dermatoses can be distinguished: inflammatory
      dermatoses without any causative organism, infections and dermatoses originating
      from cutaneous appendages, precancerous lesions, pigmented lesions and genital
      pruritus. The etiology, causative factors, clinical features and newer treatment
      options are considered. Because of local environmental factors, genital
      dermatoses often present in a different way than in other localizations.

PMID- 15724099
TI  - The mystical effects of dermatological vehicles.
AB  - Topical treatment of the skin is as old as the evolution of man. Instinctively,
      we try to treat a skin injury or irritation with cooling or soothing substances.
      Even animals lick their wounds, trusting instinctively in the healing power of
      saliva. When did this archaic pattern of treatment take the gigantic leap from
      folk medicine to modern drug therapy? This text illustrates the evolution of
      topical dermatological vehicles, their application (guidelines) and future use.
      In particular, a phenomenon that has so far been ignored in product development
      and clinical testing is the vehicle metamorphosis. In clinical and experimental
      situations, most dermatological vehicles undergo considerable changes after they
      have been removed from the primary container and are applied to the skin.
      Subsequently, the initial structural matrix, and the quantitative composition of
      the vehicle, will most likely change during and after the mechanical shear
      associated with application of the product and/or evaporation of ingredients.
      This natural, but highly dynamic process will generate mini-environments for the
      active moiety that are difficult to predict and that are crucial to the fate of
      the active moiety. Despite the reasonable wishes of formulators, clinicians,
      patients and customers, there are still no universal vehicles. Each drug, at each
      concentration, requires a different vehicle for optimized therapy. Stability and
      compatibility of excipients and active moiety are crucial for any commercially
      available pharmaceutical or cosmetic formulation, together with local and
      systemic safety of all components. Nonetheless, more diverse and molecularly
      complex classes of new dermatological vehicles are continuously being researched
      and refined. The scientific progress has been remarkable when one considers the
      simple emulsion mixtures that were commonplace in dermatological therapy and
      still persist to this day in commercial products. It is to be hoped that the
      result of these research endeavors will be the emergence of more innovative
      topical formulations, applying engineered bioavailability control systems, with
      broader applications in topical therapeutic and cosmetic vehicles.

PMID- 15724100
TI  - Teledermatology: just cool or a real tool?
AB  - Telemedicine is the practice of healthcare using interactive audio, visual and
      data communication. This includes healthcare delivery, diagnoses, consultation
      and treatment as well as education and transfer of medical data. The transmission
      of multimedia streams has remained a major challenge. Although the Internet
      remains basically insecure, technology allows today to define and implement
      complete security profiles for specific (medical) communities. Data security is a
      must as in all other areas of applied medicine. Teledermatology offers
      possibilities in consulting, continuous medical education or teleteaching. In the
      future, consulting and asking for a second opinion will be the gold standard of
      medical care. The quality of healthcare will be improved without saving direct
      costs. However, indirect costs such as time and effort for the patient and the
      citizen will be reduced.

PMID- 15724101
TI  - Mixing glycolic acid with retinaldehyde: RALGA, a technical achievement.
AB  - BACKGROUND: The use of retinaldehyde or glycolic acid was found to be effective
      in topical acne treatments. OBJECTIVE: The aim of this study was thus to take
      advantage of the possible synergistic effect between retinaldehyde and glycolic
      acid and to combine the latter in a single formulation, in other words, in an oil
      in-water emulsion. METHODS: A certain number of critical parameters were taken
      into account when designing the formulation, i.e. solubility of retinaldehyde and
      glycolic acid, pH of the finished product and insufficient stability of
      retinaldehyde notably in the presence of water. Consequently, the oil components,
      which form the oily phase of the emulsion, were carefully selected according to
      the solubility of retinaldehyde. Moreover, we aimed at obtaining adequate
      emulsion stability so that a large amount of water could be used to make the
      hydroxy acid soluble. RESULTS AND CONCLUSION: The best retinaldehyde-glycolic
      acid (RALGA) formulation developed had a low pH (around 3.5) and, when stored at
      40 degrees C, revealed a good stability. Finally, the antibacterial activity of
      this formulation was also tested in vitro against Propionibacterium acnes and
      showed antibacterial results after only 5 min of contact.

PMID- 15724102
TI  - Pharmacology of RALGA, a mixture of retinaldehyde and glycolic acid.
AB  - BACKGROUND: Retinoids and alpha-hydroxy acids (AHAs) are major compounds in
      topical therapy. They exert distinct but potentially complementary activities.
      However, their association is limited by their respective irritating potential.
      Recently, the first association between a retinoid and an AHA has been achieved;
      this formulation (RALGA) associates retinaldehyde (RAL)--a precursor of retinoic
      acid (RA)--and glycolic acid (GA)--an AHA. OBJECTIVE: To study the
      pharmacological properties of RALGA. METHODS: The bioavailability of RAL into the
      skin after topical RALGA was studied by HPLC, and its bioconversion to RA was
      analysed by measuring the enzyme activity of retinaldehyde dehydrogenase and the
      RA content in the epidermis and dermis. The retinoid activity of RALGA was
      studied on the modulation of Hhb4 keratin mRNA on the tail of C57BL/6 mice, and
      its comedolytic properties on the size and density of dermal cysts and the
      morphology of sebaceous glands in hairless mice. RESULTS: Epidermal and dermal
      concentrations of RAL and RA were higher after RALGA treatment, as compared to
      both RAL 0.1% alone and RA 0.05% alone; this indicates that the presence of GA
      favours the bioavailability and biotransformation of RAL into RA. The retinoid
      activity of RALGA (suppression of Hhb4 mRNA keratin) was similar to that of RAL
      alone, indicating that the presence of GA does not interfere with specific
      retinoid activity; GA alone had no effect in this test, which confirms the
      specificity of Hhb4 mRNA keratin modulation for retinoid activity. The diameter
      and the density of dermal cysts as well as the size of sebaceous glands were
      significantly decreased by RALGA. CONCLUSION: These observations indicate that
      the addition of an AHA such as GA to a retinoid such as RAL results in a better
      bioavailability of the retinoid, thus a higher delivery of RA, which potentiates
      the biological activities of the retinoid. This combination allows a delivery of
      high amounts of RA in the skin while preventing the side-effects usually observed
      with high concentrations of topical RA.

PMID- 15724103
TI  - Efficacy and safety of 0.1% retinaldehyde/ 6% glycolic acid (diacneal) for mild
      to moderate acne vulgaris. A multicentre, double-blind, randomized, vehicle
      controlled trial.
AB  - BACKGROUND: Retinaldehyde and glycolic acid are both efficient in acne.
      OBJECTIVE: To evaluate the efficacy and tolerability of a 0.1% retinaldehyde/6%
      glycolic acid combination (Diacneal) for mild to moderate acne vulgaris. METHODS:
      Overall physician and patient ratings of acne symptom severity and tolerance were
      performed at baseline, months 1, 2 and 3. RESULTS: Mean numbers of papules,
      pustules and comedones were significantly reduced from month 1 onwards. A
      significant advantage of Diacneal over vehicle was demonstrated on the
      percentages of patients with ongoing healing lesions at month 2, healing ancient
      lesions from month 1 and patients with 'important/very important' global
      improvement from month 2 (50.0 vs. 26.3%) confirmed by patients at month 3 (86.1
      vs. 58.8%). Products were well tolerated; only 1 patient had to stop the
      treatment. CONCLUSIONS: Diacneal, a combination of 0.1% retinaldehyde/6% glycolic
      acid, is effective and well tolerated in mild to moderate acne vulgaris.

PMID- 15724104
TI  - Topical retinaldehyde with glycolic acid: study of tolerance and acceptability in
      association with anti-acne treatments in 1,709 patients.
AB  - BACKGROUND: Retinaldehyde (RAL), a key metabolite between vitamin A and retinoic
      acid, acts by modulating differentiation and proliferation of keratinocytes,
      which is of interest in acne lesions, mainly retentional lesions. Glycolic acid
      increases the exfoliation of corneocytes explaining its mild activity on
      retentional lesions. Thus, RAL and glycolic acid combined in the same product
      (Diacneal) have complementary activities which can be of interest for acne
      patients. The aim of this study was to evaluate the tolerance of Diacneal used by
      1,709 acne patients in combination with their usual acne products except
      retinoids. RESULTS: This study demonstrated a very good tolerance of Diacneal
      when used with other acne treatments for 90 days. Complaints about side-effects
      were rare. Moreover, the significant decrease in both inflammatory and
      retentional lesions between day 0 and day 90 indicates that Diacneal could
      amplify the efficiency of other anti-acne products used at the same time by the
      patients. The subjective evaluation of the preparation's efficacy by
      investigators and patients was strongly favourable. CONCLUSION: These data show
      that a combination of RAL 0.1% and glycolic acid 6% may be used in association
      with other topical anti-acne treatments (benzoyl peroxide and topical
      antibiotics) with an excellent tolerance.

PMID- 15724105
TI  - The depigmenting effect of RALGA in C57BL/6 mice.
AB  - BACKGROUND: It has been known for a long time that the topical use of retinoic
      acid (RA) produces mild depigmentation of human skin. However, RA has two major
      disadvantages for its utilisation as a topical depigmenting compound. First, RA
      can act as an irritant and can produce considerable erythema and exfoliation of
      skin. Second, RA has a relatively weak depigmenting ability compared to other
      known depigmenting chemicals. OBJECTIVE: In this study, we show that RALGA, a
      combination of the less irritant retinoid retinaldehyde (RAL; 0.1%) and glycolic
      acid (6.4%), has a higher skin-depigmenting potential than RA 0.05% in the tail
      skin of C57BL/6 mice. This effect was observed in reducing the number of
      functioning melanocytes and/or in inhibiting their ability to synthesise melanin.
      In addition, the visually recognisable depigmenting effect of RALGA was evident
      earlier than that of RA, i.e. only after 1 week of application. RALGA may
      therefore serve as a depigmenting product for the treatment of skin
      hyperpigmentary disorders. Postacne hyperpigmented lesions represent a very
      common pigmentary problem among acne patients. RALGA may thus act as an anti-acne
      product, due to the presence of RAL--an RA precursor--which could simultaneously
      remove the postacne hyperpigmented lesions in such patients.

PMID- 15724106
TI  - RALGA (Diacneal) decreases melanin content in a human skin model.
AB  - BACKGROUND: Retinaldehyde and glycolic acid RALGA (Diacneal) are both effective
      in the topical treatment of acne. A decrease in the postinflammatory pigmentation
      has been observed after application of Diacneal during 3 months. AIM: To verify
      the effect of this association on pigmentation using an original model of
      surviving human skin. METHODS: Human skin explants were maintained alive in organ
      culture for 14 days. Diacneal was applied every day. Pigmentation of skin,
      depending on the transfer of melanosomes from melanocytes to keratinocytes, was
      visualized histologically by Fontana-Masson staining. The number of melanocytes
      was determined after the DOPA reaction. RESULTS: A decrease in melanin content
      was shown after application of Diacneal. The number of melanocytes was not
      modified. CONCLUSION: These results suggest that RALGA (Diacneal) may be of
      interest to prevent the postinflammatory pigmentation of acne.

PMID- 15724107
TI  - RALGA (Diacneal), a retinaldehyde and glycolic acid association and
      postinflammatory hyperpigmentation in acne--a review.
AB  - Acne vulgaris affects 3 out of 4 adolescents and usually vanishes at the end of
      puberty with either no sequelae or mild to moderate sequelae, such as
      postinflammatory hyperpigmenation (PIH), which may result in psychological and
      emotional damages. The poor tolerability of the actual treatments (secondary
      inflammation) is a hindrance to therapy. Retinaldehyde (RAL), a precursor of
      retinoic acid, has shown depigmenting activity. Glycolic acid (GA) decreases the
      excess of pigment by a wounding and re-epithelization process. Thus, a
      synergistic effect was expected from the combination of RAL 0.1% and GA 6% RALGA
      (Diacneal) in the treatment of acne vulgaris and PIH. Efficacy results of
      preclinical and clinical trials tend to confirm the expectations for both acne
      and PIH treatment. A good tolerability was observed. In conclusion, the cosmetic
      cream Diacneal is a well-tolerated treatment for the prevention and healing of
      PIH in acne patients.

PMID- 15724108
TI  - Reports on defense styles in depression.
AB  - INTRODUCTION: 'State effect' of depression on personality makes its assessment
      during depression difficult. Many clinicians do not only refer to the patient,
      but use additional information sources, especially reports from close informants.
      Our hypothesis was that an informant could assess the defensive functioning of
      the depressed patient. The objective of this study was to investigate the
      validity of the informants' assessment of defense styles in depressed patients.
      METHODS: Sixty-three inpatients with DSM-IV major depression as primary diagnosis
      were included. They were administered the Defense Style Questionnaire (DSQ) at
      admission (D0) and 28 days after treatment (D28) according to their current
      state. At the same time, informants rated an adapted version of the DSQ (INF
      DSQ), according to the patient's current (D0 and D28) and premorbid defensive
      functioning (D0). Otherwise, severity of depression was assessed using the 17
      item Hamilton Depression Rating Scale at D0 and D28. RESULTS: Agreement between
      patient's and informant's DSQ scores was moderate, both at D0 and D28, even if
      comparison of mean defense scores does not show significant difference. Mature
      defense scores significantly increased between D0 and D28, whereas immature
      defense scores significantly decreased, with both the DSQ and INF-DSQ. During the
      episode, informants are able to discriminate premorbid from current D0 defenses,
      but not from current D28 defenses. CONCLUSION: Even if this study has strong
      limitations, our results argue for the interest of close informants to assess
      premorbid personality. Before it could be validated, the INF-DSQ should be
      further studied in other subgroups of patients, especially its ability to give
      accurate descriptions of patient's premorbid defenses during an acute episode.

PMID- 15724109
TI  - Frameless stereotactic ventricular shunt placement for idiopathic intracranial
      hypertension.
AB  - INTRODUCTION: Cerebrospinal fluid (CSF) shunting effectively reverses symptoms of
      idiopathic intracranial hypertension (IIH). Lumboperitoneal (LP) shunts have
      traditionally been used in patients with IIH due to a frequently undersized
      ventricular system. However, the advent of image-guided stereotaxis has enabled
      effective ventricular catheter placement in patients with IIH. We describe the
      first large series of frameless stereotactic ventriculoperitoneal (VP) shunting
      for patients with slit ventricles and IIH. METHODS: We describe the frameless
      stereotactic VP shunting technique for IIH in 32 procedures. Outcomes following
      shunt placement, time to shunt failure, and etiology of shunt failure are
      reported. RESULTS: A total of 21 patients underwent 32 ventricular shunting
      procedures (20 VP, 10 ventriculoatrial, 2 ventriculopleural). One hundred percent
      of shunts were successfully placed into slit ventricles, all requiring only one
      pass of the catheter under stereotactic guidance to achieve the desired location
      and CSF flow. There were no procedure-related complications and each ventricular
      catheter showed rapid egress of CSF. All (100%) patients experienced significant
      improvement of headache immediately after shunting. Ten percent of ventricular
      shunts failed at 3 months after insertion, 20% failed by 6 months, 50% failed by
      12 months, and 60% failed by 24 months. Shunt revision was due to distal
      obstruction in 67%, overdrainage in 20%, and distal catheter migration or CSF
      leak in 6.5%. There were no shunt revisions due to proximal catheter obstruction
      or shunt infection. CONCLUSIONS: In our experience treating patients with IIH,
      frameless stereotactic ventricular CSF shunts were extremely effective at
      treating IIH-associated intractable headache, and continued to provide relief in
      nearly half of patients 2 years after shunting without many of the shunt-related
      complications that are seen with LP shunts. Placing ventricular shunts using
      image-guided stereotaxis in patients with IIH despite the absence of
      ventriculomegaly is an effective, safe treatment option.

PMID- 15724110
TI  - [Treatment results of pseudarthrosis of the humeral shaft by open reduction and
      internal fixation with dynamic compression plating].
AB  - OBJECTIVES: We evaluated the results of open reduction and internal fixation with
      the use of dynamic compression plating in patients with pseudarthrosis of the
      humeral shaft. METHODS: Eighteen patients (12 males, 6 females; mean age 41
      years; range 22 to 68 years) with aseptic pseudarthrosis of the humeral shaft
      were treated by open reduction and internal fixation with the use of a dynamic
      compression plate following unsuccessful treatment with conservative (n=7) or
      surgical (n=11) methods. The mean interval between the initial and final
      treatments was 12.2 months (range 5 t 46 months). Exploration of the radial nerve
      and autogenous corticocancellous grafting were simultaneously performed in all
      the cases. Functional results were evaluated according to the Stewart-Hundley's
      criteria. The mean follow-up was 38.8 months (range 12 to 78 months). RESULTS:
      Union was achieved in all (94.4%) but one patient within a mean duration of 5.5
      months (range 3 to 8 months). Functional results were good in fourteen patients
      (77.8%), fair in three patients (16.7%), and poor in one patient (5.6%). Radial
      nerve palsy that occurred in two patients during the early postoperative period
      underwent spontaneous recovery within three and five months, respectively. Mild
      reflex sympathetic dystrophy developed in two patients. CONCLUSION: In selected
      patients with pseudarthrosis of the humeral shaft, the results of open reduction
      and internal fixation with the use of dynamic compression plating are excellent,
      provided that an appropriate surgical technique is employed.

PMID- 15724111
TI  - [An evaluation of knee ligament injuries encountered in skiers at the Uludag Ski
      Center].
AB  - OBJECTIVES: We evaluated the frequency, anatomic types, and predisposing factors
      of knee ligament injuries that occur in skiers during a winter season at the
      Uludag Ski Center, Bursa, Turkey. METHODS: A total of 215 patients (240 knees)
      presented to the Uludag University-Sabanci Health Center after sustaining a skier
      knee injury during the 2003-2004 winter season. The mean patient age was 31 years
      (range 9 to 55 years). Knee ligament injuries were assessed according to the
      AOSSM (American Orthopaedic Society for Sports Medicine) criteria. Cumulative
      data were collected from patient records and from a questionnaire administered to
      100 healthy skiers. RESULTS: The mean knee injury rate was 1.14 injuries per 1000
      skier-days. The mean length of time between the occurrence of knee injuries was
      875 skier-days. The most frequently injured ligament was the interior cruciate
      ligament (35.4%) followed by the anterior cruciate ligament (27.1%). Knee
      ligament injuries were significantly more common in skiers than in snowboarders
      (odds ratio 6.83, p<0.001). Hard and steep pists were associated with a two-fold
      risk for knee ligament injuries (odds ratio 2.28, p<0.001). For the occurrence of
      knee injuries, no significant differences were found with respect to sex and age.
      CONCLUSION: The interior and the anterior cruciate ligaments are the most
      commonly injured ligaments in skiers. Two risk factors concerning the equipment
      (ski) and the environment (hard pists) play a significant role in the occurrence
      of knee injuries.

PMID- 15724112
TI  - [The results of single-stage multilevel muscle-tendon surgery in the lower
      extremities of patients with spastic cerebral palsy].
AB  - OBJECTIVES: We evaluated the results of single-stage multilevel muscle-tendon
      surgery performed for the treatment of contractures in the lower extremities of
      patients with spastic cerebral palsy. METHODS: The study included 23 patients (11
      girls, 12 boys; mean age 6 years 3 months; range 4 to 17 years) with spastic
      cerebral palsy, who underwent single-stage multilevel muscle-tendon surgery for
      the treatment of contractures in the lower extremities secondary to spasticity.
      Quadriplegia, diplegia, and hemiplegia were present in five, 14, and four
      patients, respectively. Preoperatively, 13 patients could walk, while 10 patients
      lacked ambulation even with support. Evaluations were based on pre- and
      postoperative (mean 4 years 9 months; range 1 to 8 years) physical examination
      findings and on the Gross Motor Function Classification System (GMFCS) scores.
      The patients' mean age at the last follow-up was 11.5 years (range 9 to 19
      years). RESULTS: The range of motion of all the operated joints improved
      postoperatively, resulting in significant improvements in posture, sitting, gait,
      and hygiene of the patients. Of ten patients who could not walk, five could
      ambulate with the use of a walker or crutches postoperatively. The mean pre- and
      postoperative GMFCS scores were 3.045 and 1.864, respectively (p<0.001). All the
      patients showed an improvement of at least one GMFCS level. CONCLUSION: Surgery
      for spastic cerebral palsy can be most beneficial only when all contractures of
      the hip, knee, and ankle have been corrected. Symmetrical and multilevel
      operations should be performed when necessary, for single-stage and symmetrical
      multilevel muscle-tendon surgical applications have definite advantages over
      staged interventions.

PMID- 15724113
TI  - [The role of electrophysiologic tests in the early diagnosis of posterior
      interosseous neuropathy in patients thought to have lateral epicondylitis].
AB  - OBJECTIVES: We investigated the role of electrophysiologic tests in determining
      posterior interosseous neuropathy (PIN) in patients with a preliminary diagnosis
      of lateral epicondylitis. METHODS: Thirty-three patients (24 females, 9 males;
      mean age 49 years) with a preliminary diagnosis of lateral epicondylitis and 15
      healthy controls (10 females, 5 males; mean age 48 years) underwent radial,
      median, and ulnar nerve conduction studies, electromyography (EMG) of some
      selected muscles, and measurements for grip strength. The duration of symptoms
      was less than a month in all the patients and no therapy was instituted. RESULTS:
      A diagnosis of PIN was made in 22 patients (66.7%). The mean ages of the patients
      with and without PIN were 45 and 51 years, respectively. The mean grip strengths
      did not differ significantly between the patients and controls, and between the
      right and left hands. All the patients responded well to conservative treatment.
      CONCLUSION: Electrophysiologic tests may be necessary and beneficial in the
      differential diagnosis of PIN in patients unresponsive to treatment for lateral
      epicondylitis of early stage.

PMID- 15724114
TI  - [The mid-term results of minimal medial epicondylectomy and decompression for
      cubital tunnel syndrome].
AB  - OBJECTIVES: We evaluated the mid-term follow-up results of patients who were
      treated by minimal epicondylectomy and decompression for cubital tunnel syndrome.
      METHODS: The study included 17 elbows of 15 patients (9 females, 6 males; mean
      age 45 years; range 35 to 63 years) who underwent minimal medial epicondylectomy
      and in situ decompression for cubital tunnel syndrome, which was diagnosed
      through history, physical examination, and electrodiagnostic tests. Before
      surgery, all the patients received various conservative treatments for at least
      six months, with no beneficial effect. Thirteen patients had unilateral, two
      patients had bilateral involvement, with 11 elbows on the dominant side. The mean
      duration of symptoms was 14 months (range 3 to 36 months). Preoperative grading
      of nerve compression according to the McGowan system was as follows: three
      patients (20%) grade I, 11 patients (73.3%) grade II, and one patient (6.7%)
      grade III. The results of surgical treatment was evaluated according to the
      Wilson-Krout criteria. The mean follow-up was 32 months (range 25 to 64 months).
      RESULTS: Symptomatic improvement was achieved in all the patients. The results
      were excellent in 11 elbows (64.7%), good in five elbows (29.4%), and fair in one
      elbow (5.9%). None of the patients developed ulnar nerve palsy or subluxation,
      medial elbow instability, or weakness of the flexor-pronator origin. Pain and
      tenderness detected at the osteotomy site in four elbows disappeared after a mean
      of three months. CONCLUSION: Minimal medial epicondylectomy and decompression was
      found to be a safe and effective method with a low complication rate in the
      treatment of cubital tunnel syndrome.

PMID- 15724115
TI  - [Long-term results of autograft and allograft applications in hand enchondromas].
AB  - OBJECTIVES: We evaluated the long-term results of treatment with curettage
      followed by an autograft or allograft application in patients with enchondroma of
      the hand. METHODS: Within a 15-year period, 76 patients (41 males, 35 females;
      mean age 32 years; range 14 to 47 years) were operated on for enchondroma of the
      hand. Following curettage of the lesion, reconstruction of the defect was made
      either by an autograft obtained from the iliac crest (n=76) or by a dehydrated
      cancellous allograft (n=15). The diagnosis was histologically confirmed in all
      the cases. Functional and radiographic results were assessed according to the
      Enneking scoring system and the Tordai classification system, respectively. The
      mean follow-up periods were 13.5 years (10-22 years) and 7.4 years (6-11 years)
      in autograft and allograft applications, respectively. RESULTS: Consolidation of
      the autografts took a mean of 38 days and maximum grasp force was obtained in a
      mean of 46 days. These periods were 51 and 55 days, respectively, for the
      allografts. Functional results were excellent/very good in 64%, good in 23%, and
      poor in 13.1% with autografts; radiographically, 78.7% of the patients were in
      group I, 18% were in group II, and 3.3% were in group III. Of the allograft
      group, the results were excellent/very good in 66.7%, good in 26.7%, and poor in
      6.7%. Radiographically, 80%, 13.3%, and 6.7% of the patients were classified in
      group I, II, and III, respectively. There were two recurrences in the autograft
      group, while one patient, in the allograft group, who had multiple
      enchondromatosis required a ray amputation because of malignant transformation.
      CONCLUSION: Autograft and allograft applications seem to yield similar success
      rates in the treatment of enchondroma of the hand.

PMID- 15724116
TI  - [The prevalance of orthopedic disabilities in the district of Cay, Afyon,
      Turkey].
AB  - OBJECTIVES: Data were collected on disabilities from a sample population in order
      to estimate the prevalence of orthopedic disabilities in the general population.
      METHODS: A two-stage field study was conducted in Cay, a district of Afyon,
      Turkey. In the first stage, a list of all individuals with orthopedic
      disabilities was derived. Then, medical histories were elicited and examinations
      were made by a team of specialists of orthopedics and traumatology. Radiographic
      studies were made when necessary. Orthopedic disabilities were defined as any
      muscle or skeletal abnormality that was associated with a permanent functional
      loss and were classified as congenital, traumatic, cerebral palsy, poliomyelitis,
      and other causes. RESULTS: The overall population was 35,571, of whom 189 had
      orthopedic disabilities (53/10,000). The male-to-female ratio was 1.8. The most
      common cause was congenital diseases (25.9%; 13.7/10,000), followed by trauma
      (23.8%; 12.6/10,000), cerebral palsy (21.7%; 11.5/10,000), poliomyelitis (10.1%;
      5.3/10,000), and others (18.5%; 9.8/10,000). The lowest mean age (19+/-5 years)
      was found in those with cerebral palsy, which was associated with the highest
      degree of functional loss. The mean age in patients with poliomyelitis was 29+/-7
      years. It was found that 37% of the disabled could benefit from either a limited
      or extensive surgical intervention, and 9% could have significant improvement
      both in functional ability and life quality through physical therapy or the use
      of a prosthesis/orthosis. Only 18% were under the coverage of a health insurance,
      though. CONCLUSION: The data of this study may throw some new light on the
      prevalence and implications of orthopedic disabilities in Turkey.

PMID- 15724117
TI  - [The chondroprotective effect of intra-articular hyaluronic acid at early stages
      of osteoarthritis: an experimental study in rabbits].
AB  - OBJECTIVES: Hyaluronic acid (HA) is used in osteoarthritis, especially for the
      control of pain. In this study, we investigated the effect of intra-articular HA
      on experimental osteoarthritis of early stage. METHODS: Osteoarthritis was
      induced in both knees of 10 rabbits by transecting the anterior cruciate ligament
      under intramuscular anesthesia with ketamine and xylazine. Intra-articular HA at
      a dose of 0.6 ml (15 mg/ml) and physiologic saline solution (0.6 ml) were
      injected into the right and left knees, respectively, three times with a week
      interval. Three rabbits died during the study period and were excluded. The
      remaining rabbits were sacrificed in the 12th week via high dose anesthesia to
      remove the distal femora for histological evaluation using the Mankin scale and
      for measurements of the cartilage area. RESULTS: The mean cartilage areas
      calculated in HA- and saline-injected knees differed significantly (1.097 mm2 and
      0.477 mm2, respectively; p<0.05). The overall mean Mankin score was significantly
      lower in HA-injected knees (3.57 versus 11.14; p<0.05). Although, there were no
      significant differences between the two groups with respect to cellular
      abnormality, matrix staining, and tidemark continuity (p>0.05), the mean scores
      for the structure of the cartilage were significantly different (0.86 versus
      4.43; p<0.05). The integrity of the tidemark was preserved in all the HA
      administered knees, though a notable disruption was observed in four control
      knees. CONCLUSION: Our results suggest that HA delays the development of
      osteoarthritis at early stages through exerting a chondroprotective effect.

PMID- 15724118
TI  - [The development of osteosarcoma following radiotherapy for fibrous dysplasia].
AB  - Sarcoma arising from fibrous dysplasia (FD) is rare and it is more common in
      polyostotic type. In this case report, we present a 41-year-old male patient who
      developed osteosarcoma of the left tibia 28 years after the initial diagnosis and
      20 years after radiation therapy for FD. He underwent above-knee amputation, but
      died eight months after surgery. This case suggests that radiotherapy has no
      beneficial effect in the treatment of FD and that it may be associated with the
      development of sarcoma.

PMID- 15724119
TI  - [Tibial osteomyelitis following intraosseous infusion: a case report].
AB  - Fluids, medications, and blood products can be rapidly administered via
      intraosseous infusion under emergency conditions, particularly to pediatric
      patients aged from 0 to 2 years. A five-month-old infant who had been
      hospitalized with a diagnosis of sepsis developed swelling and hyperemia at the
      infusion site 10 days after an intraosseous infusion in the right proximal tibia.
      Physical examination showed a serous discharge from a fistula on the anteromedial
      side of the right proximal cruris. Plain radiographs demonstrated periosteal
      reaction in the right tibia and osteolytic areas in the proximal metaphysis. With
      a diagnosis of acute osteomyelitis, drainage and medullary irrigation were
      performed and parenteral antibiotic treatment was initiated. Cultures from the
      surgical site yielded Candida albicans, upon which fluconazole (8 mg/kg)
      treatment was administered for four weeks. A complete clinical and radiographic
      improvement was observed at the end of a 12-month follow-up.

PMID- 15724120
TI  - [Delayed diagnosis of isolated ulnopalmar dislocation of the fifth
      carpometacarpal joint and its treatment with open reduction and internal
      fixation].
AB  - We present a 21-year-old male patient with an isolated ulnopalmar dislocation of
      the fifth carpometacarpal joint that occurred due to a fall on the hand.
      Diagnosis was delayed for five weeks and closed reduction was not successful. He
      was treated with open reduction and internal fixation. Upon removal of fixation
      materials six weeks after surgery, he developed reflex symphatic dystrophy and
      limitation in joint movements, which disappeared following rehabilitation and
      medical treatment at the end of 15 weeks. Functional and radiographic results
      were satisfactory.

PMID- 15724121
TI  - How can we analyse the role of family medicine using the principles of evidence
      based medicine?

PMID- 15724122
TI  - Primary care research: not a lost cause but still struggling to find its feet.

PMID- 15724123
TI  - Towards improving the accuracy of diagnosing asthma in early childhood.
AB  - OBJECTIVES: Early and correct diagnosis of asthma in wheezing children is
      essential for early treatment and prevention of under- or over-treatment. The aim
      was to study whether combining frequency and age of onset of wheezing illness
      with respiratory and atopic morbidity at age 0-6 years and sociodemographic
      parameters for asthma might be helpful for the general practitioner to diagnose
      asthma early and accurately. METHODS: Birth cohort, mean follow-up 20 years (SD
      4.8) in general practice. The outcome, adolescent asthma, was analysed in
      relation to wheezing and non-wheezing respiratory and personal and familial
      atopic morbidity. All diagnoses were from the Continuous Morbidity Registration
      of the Department of General Practice of the University of Nijmegen, the
      Netherlands. RESULTS: 1586 (64%) of the children could be followed. Adolescent
      asthma occurred in 6.4%. There were indications for under- and over-diagnosis of
      asthma at age 0-6 years. Non-recurrent wheezing (only one episode) and recurrent
      wheezing (>or =2 episodes) in the first three years of life, and recurrent
      wheezing at age 4-6 increased the risk with odds ratios (95% confidence interval)
      of 3.3 (1.9-5.6), 4.7 (2.8-8.2) and 15.4 (7.1-33.7), respectively. The risk
      additionally increased independently with a family history for asthma, (2.0 [1.1
      3.6]), atopic dermatitis (1.7 [1.1-2.7]) and sinusitis (2.9 [1.3-6.4]) and
      decreased for > or =2nd born children (0.38 [0.19-0.47]) and those with a low
      social-economic status (0.61 [0.39-0.94]). CONCLUSION: Easily available history
      and clinical data may facilitate the early diagnosis of asthma in children with
      wheezing illness.

PMID- 15724124
TI  - Binners, fillers and filers--a qualitative study of GPs who don't return postal
      questionnaires.
AB  - BACKGROUND AND OBJECTIVES: Postal questionnaires are a frequently used method of
      obtaining information from general practitioners. However, getting GPs to return
      questionnaires or participate in research can be challenging. We wanted to
      ascertain reasons why GPs identified as 'routine non-responders' to postal
      questionnaires, do not participate in this type of research. METHODS: Qualitative
      study using semi-structured interviews of 14 GPs who had returned only one or
      none of five questionnaires sent to them during a five-year period between 1994
      1999. RESULTS: Participants were classified into one of three groups--binners,
      filers and fillers--according to their behavior when faced with a questionnaire.
      Each group had slightly different attitudes toward research in general practice.
      Although standard strategies such as incentives and good design could influence
      the decision to complete a questionnaire, poor research experiences or a poor
      relationship between the participant and researchers were also very important.
      CONCLUSION: The decision not to return a postal questionnaire is multifactorial
      and reflects personal and professional attitudes, experiences and organisation of
      individual GPs as well as time pressure and interest. The development of a
      positive relationship with a researcher or academic department may be influential
      in encouraging the return of postal questionnaires and when trying to enhance
      response rates amongst 'routine non-responders' researchers should take into
      account the broader values ans practices GPs bring to their work.

PMID- 15724125
TI  - Management of acute cough: comparisons between Belgian and Dutch GPs.
AB  - OBJECTIVES: In Europe there are large variations in overall outpatient antibiotic
      use, even between two neighbouring countries as Belgium and the Netherlands. We
      aimed to compare the management of acute cough between Belgian and Dutch general
      practitioners (GPs). METHODS: In cross-sectional studies in Belgium and the
      Netherlands, 71 Belgian and 84 Dutch GPs included adult patients consulting for
      acute cough. Differences in antibiotic prescription rates, the percentage of
      first-choice antibiotics (i.e. tetracyclines and broad-spectrum penicillins) and
      bronchodilator prescription rates were assessed by using Generalised Estimates
      Equations to adjust for clustering of patients within GPs. RESULTS: In Belgium
      324/810 patients (40%) were prescribed an antibiotic compared with 101/309 (33%)
      in the Netherlands (adjusted OR (95% CI) 1.28 (0.91-1.83)). Belgian GPs
      prescribed fewer first-choice antibiotics compared with Dutch GPs: 124/324 (38%)
      versus 67/101 (66%) (adjusted OR (95% CI) 0.39 (0.22-0.72)). In both countries,
      17% of the patients were prescribed a bronchodilator. CONCLUSIONS: Antibiotic
      prescription rates for adult patients with acute cough were not significantly
      higher in Belgian than in Dutch general practice at the 5% significance level.
      Dutch GPs' antibiotic prescriptions were more in line with national guidelines.
      Bronchodilator prescription rates were similar. Because Dutch GPs probably
      encountered more severe cases of acute cough compared with their Belgian
      colleagues, the observed prescribing differences might be underestimated.

PMID- 15724126
TI  - Implementation of a pilot programme for screening for chlamydial infection in
      general practice.
AB  - OBJECTIVES: To determine whether opportunistic screening for Chlamydia
      trachomatis, based on a selective screening, algorithm, is possible in general
      practice in Belgium; to assess feasibility of the screening strategy with respect
      to workload, acceptability, and organisational aspects. METHODS: Implementation
      of a pilot screening programme by 37 GPs for a period of 15 weeks. GPs' screening
      practices were registered and compared with the guidelines they had received.
      Outcome measures were: the number of patients included in the risk assessment,
      uptake of screening by eligible patients, prevalence of previously unidentified
      infection, and uptake of treatment. After the study period GPs evaluated a number
      of feasibility issues on a scoring form. RESULTS: 326 women underwent the risk
      assessment and 214 were tested by an amplification assay on a urine sample.
      Prevalence in woman at risk was 6.4%. Overall effective screening rate was 77.6%;
      9 of 11 positives took up treatment. Participating GPs found the strategy
      feasible and perceived that it was well accepted by their patients. DISCUSSION:
      The screening strategy was easily implemented by most GPs but some of them
      dropped out. The guidelines were followed relatively well and there were no major
      logistic problems. The uptake of treatment wat suboptimal. Efforts must be made
      to stimulate and educate more GPs to perform screening; laboratory and storage
      conditions should be optimised; refunding criteria should be revised; and
      overscreening must be avoided.

PMID- 15724127
TI  - Diagnosing depression: what's in a name?
AB  - BACKGROUND: Large and undeclared differences exist between incidence and
      prevalence rates of depression in general practice based morbidity registries,
      and in registries based on questionnaires of questionnaire-based interviews. We
      tried to identify possible explanations for these differences. METHOD: Literature
      based discussions were held among a multidisciplinary group of clinicians and
      researchers. FINDINGS: Selection bias and imperfections in the diagnostic
      capabilities of each of the systems may play a role, but they are insufficient
      explanations for the differences that were identified. Questionnaires provide
      factual information on a patient's situation. Frequently no information is
      available on the intensity or consistency of the symptoms and on the personal
      growth or coping strategies that were developed by the patient. GPs may register
      depressive complaints as part of other psychological problems to which the
      depression is related. Their diagnostic strategy is part of a process to identify
      those who can benefit from specific interventions. In general practice,
      depression is a diagnosis that tends to emerge progressively. Depression can be
      considered as a way of coping with events. DSM-based questionnaires provide
      information that is more related to a latent characteristic of a personality,
      rather than a temporal, inappropriate expression of this characteristic, as
      identified in a clinical diagnosis. INTERPRETATION: Conceptual differences and
      different objectives when diagnosing, more than selection bias or diagnostic
      imperfections, tend to be responsible for the identified differences in
      occurrence rates of depression.

PMID- 15724129
TI  - Cross-sectional study on quality of life, work demands and psychosocial stress of
      Lithuanian general practitioners.

PMID- 15724131
TI  - The present of nuclear cardiology: a great past opens the way to a bright future.

PMID- 15724128
TI  - Preferred antibiotics, dosages and length of treatments in general practice--a
      comparison between ten European countries.

PMID- 15724132
TI  - The many ways to myocardial perfusion imaging.
AB  - Myocardial perfusion imaging (MPI) is important for the management of patients
      with suspected or known coronary artery disease (CAD). Nuclear cardiology is the
      most widely used noninvasive approach for the assessment of myocardial perfusion.
      The available single-photon emission computed tomography (SPECT) flow agents are
      characterized by a rapid myocardial extraction and by a cardiac uptake
      proportional to blood flow. In addition, different positron emission tomography
      (PET) tracers may be used for the quantitative measurement of myocardial blood
      flow and coronary flow reserve. The decrease in blood flow, determined by
      coronary artery stenosis, produces myocardial ischemia leading to perfusion
      abnormalities detectable by SPECT or PET in the early phase of ischemia. Other
      imaging techniques, such as contrast echocardiography and magnetic resonance
      imaging (MRI) have been more recently proposed as alternative methods for the
      evaluation of myocardial perfusion. Although several technical aspects have to be
      better defined to use contrast echocardiography in clinical practice, this
      approach appears promising for the evaluation of myocardial perfusion. MRI has
      also been proposed for the assessment of myocardial perfusion by measuring the
      alteration of regional myocardial magnetic properties after the intravenous
      injection of contrast agents. Due to the high contrast and spatial resolution of
      the technique, MRI allows differentiating sub-endocardial and sub-epicardial
      perfusion, emerging as a potential alternative non-ionizing technique to evaluate
      myocardial perfusion. This review illustrates the noninvasive imaging modalities
      for the evaluation of myocardial perfusion, underlying advantages and
      disadvantages of each technique.

PMID- 15724133
TI  - Gated single-photon emission computed tomography. The present-day ''one-stop
      shop'' for cardiac imaging.
AB  - Gated single-photon emission computed tomography (SPECT) is the current state-of
      the-art approach to myocardial perfusion imaging. Initially, major emphasis was
      given to the improvement in diagnostic accuracy of myocardial perfusion imaging
      for the detection of coronary artery disease, because the evaluation of wall
      motion and thickening allows the recognition of attenuation artifacts and
      increases the observer's confidence. Different processing algorithms make
      possible to perform a reproducible and reliable assessment of left ventricular
      (LV) function, which has been extensively validated against various reference
      METHODS: Several articles report the additional value of functional data derived
      from gated SPECT to increase the accuracy of myocardial perfusion imaging in
      particular patient groups, such as women, to enhance the detection of multivessel
      coronary artery disease, and to permit the recognition of severe stenosis. An
      extensive literature indicates that gated SPECT allows a more accurate and
      reliable prognostic stratification of patients with known coronary artery
      disease. More recently, the peculiar contribution of gated SPECT in the
      assessment of myocardial viability has been demonstrated, with the possibility to
      evaluate in a single myocardial perfusion study the presence of preserved tracer
      uptake and the amount of contractile reserve through the acquisition of gated
      SPECT during inotropic stimulation with dobutamine. The most recent advance in
      the application of gated SPECT is the use of this technique for the reproducible
      assessment of LV functional changes, at follow-up or during inotropic
      stimulation, with perfusion data in the background. Various clinical settings,
      such as assessment of response to medical or resynchronization therapy in dilated
      or ischemic cardiomyopathy, prediction of outcome in chronic coronary artery
      disease with LV remodeling, evaluation of different treatment strategies in acute
      myocardial infarction, could take advantage from the unique combination of
      perfusion and functional data made possible by the use of gated SPECT. In
      conclusion, myocardial perfusion imaging with gated SPECT is a convincing reality
      in the field of cardiac imaging and has a still largely unexplored potential for
      a wider use in heart disease.

PMID- 15724134
TI  - Attenuation correction: eternal dilemma or real improvement?
AB  - SPECT myocardial perfusion imaging is a clinical standard for the care of cardiac
      patients. During the past 2 decades, this method has continued to evolve and
      significant improvements in image quality have been realized. Despite these
      continued improvements, imaging artifacts remain problematic and often confound
      accurate image interpretation. The most frequent and difficult cause of
      myocardial perfusion imaging artifacts continues to be related to soft tissue
      attenuation and resultant photon attenuation. Methods for non-uniform attenuation
      correction have progressed slowly until recently, but there are now a number of
      techniques, which offer true correction for photon attenuation. Clinical
      validation has demonstrated clear clinical benefits for this technology and the
      field of nuclear cardiology enthusiastically supports these technical advances.
      However, additional clinical validation is warranted especially for commercially
      available systems that have not yet been evaluated with rigor.

PMID- 15724135
TI  - The present role of nuclear cardiology in clinical practice.
AB  - Many advances have been made in the field of nuclear cardiology in the past
      decade for enhancing the diagnostic and prognostic value of stress myocardial
      perfusion imaging and the assessment of myocardial viability using SPECT
      technology. Gated SPECT for determining regional and global function have
      provided incremental diagnostic and prognostic information in the evaluation of
      patients with suspected or known coronary artery disease. Left ventricular
      ejection fraction and regional myocardial wall thickening can now be
      simultaneously evaluated with regional perfusion particularly with the use of the
      (99m)Tc-labeled perfusion agents such as sestamibi and tetrofosmin. Many studies
      have shown that the extent and severity of stress-induced perfusion defects have
      incremental prognostic value over exercise electrocardiographic stress test
      variables alone. Patients with normal perfusion scans have <1% combined cardiac
      death and myocardial infarction rates per year and thus have an excellent
      prognosis. Diabetics are particularly benefited from stress perfusion imaging for
      detection of coronary artery disease and risk assessment. Diabetics have a worse
      prognosis than nondiabetics for the same amount of hypoperfusion on stress SPECT
      studies. Quantitative rest perfusion imaging with (201)Tl or with one of the
      (99m)Tc-labeled imaging agents, or PET imaging with (18)F-deoxyglucose can
      accurately distinguish viable from irreversibly injured myocardium providing
      useful information for identifying which patients with ischemic cardiomyopathy
      benefit most from coronary revascularization with a subsequent improvement in
      left ventricular function and enhanced survival. Finally, serial stress perfusion
      imaging can be employed to monitor the efficacy of medical therapy that improves
      endothelial function and myocardial blood flow reserve.

PMID- 15724136
TI  - Nuclear cardiology in acute coronary syndromes.
AB  - Acute coronary syndromes are a frequent manifestation of coronary artery disease,
      usually being associated with chest pain and presenting as a medical emergency.
      Since a considerable number of patients with chest pain, however, have a non
      cardiac etiology of their pain, properly triaging these patients represents a
      diagnostic challenge for physicians in the emergency department. As the available
      diagnostic procedures have limited accuracy, many different diagnostic strategies
      have been evaluated. Among these, radionuclide myocardial perfusion imaging (MPI)
      at rest or in combination with stress procedures has been investigated in many
      trials. MPI has been proven to be useful, especially in a patient population with
      a low to intermediate probability of an ischemic event. Perfusion scintigraphy
      has a high sensitivity in the detection of myocardial infarction and reveals an
      excellent negative predictive value, allowing a safe discharge strategy of
      patients with a negative scan result. Moreover, it enables risk stratification
      and provides incremental and independent prognostic information regarding short
      to long term future cardiac adverse events. Several cost effectiveness studies
      have shown that perfusion imaging leads to lower overall direct costs, mainly by
      a reduction of unnecessary hospital admissions and diagnostic angiograms, without
      worsening of the clinical outcome of these patients. As a possible study
      endpoint, myocardial perfusion imaging in the acute setting enables the
      quantification of salvaged myocardium and therefore the evaluation of treatment
      efficacy. Besides perfusion agents, several infarct avid radiopharmaceuticals
      have been developed, which in part show promising results. However, larger
      randomized trials evaluating these tracers in clinical settings are needed to
      warrant routine clinical application.

PMID- 15724137
TI  - Coronary artery disease. The other half of the heaven.
AB  - Coronary artery disease (CAD) is the leading cause of death in both men and women
      in the United States as well as in most of the industrialized world. Emerging
      data have displayed important sex-based differences in CAD: its pathophysiology,
      clinical presentation, diagnostic strategies, response to therapies, and adverse
      outcomes. Although the incidence of CAD has doubled among women in the past
      decade, and the rate of women referred to diagnostic testing and
      revascularization has increased, this disease in female population is still
      identified less often, at a later stage and treated less aggressively than in
      men. Significant advances have been made in scintigraphic myocardial perfusion
      imaging for detection of ischemia, determination of prognosis, assessment of
      viability and evaluation of the efficacy of revascularization. With the
      introduction of technetium-99m perfusion agents, gated single photon emission
      computed tomography and attenuation correction, myocardial perfusion imaging in
      women has achieved as high sensitivity and specificity for the detection of CAD
      as that observed in men and can be considered an adequate noninvasive test to
      follow-up women with heart disease.

PMID- 15724138
TI  - Assessment of myocardial viability in chronic ischemic heart disease: current
      status.
AB  - Assessment of myocardial viability is clinically important in the work-up of
      patients with ischemic cardiomyopathy. Numerous studies in the past 2 decades
      demonstrated that revascularization improves left ventricular ejection fraction
      (LVEF), heart failure symptoms and prognosis in patients with viable myocardium.
      Conversely patients without viable tissue do not benefit from revascularization.
      Also, a substantial amount of viable myocardium (at least 25% of the left
      ventricle) is needed to result in improvement of LVEF. Hence, both identification
      and quantification of the extent of viable myocardium are required for a careful
      selection of candidates for revascularization. Indeed, the presence of a
      substantial amount of viable myocardium decreases the risk of surgery in patients
      with reduced LVEF. Several diagnostic techniques are available to identify
      myocardial viability. Positron emission tomography (PET), myocardial perfusion
      imaging, and stress echocardiography are considered the traditional techniques to
      evaluate myocardial viability. Recently, newer techniques including cardiac
      magnetic resonance (CMR), myocardial contrast echocardiography (MCE) and
      electromechanical mapping have been introduced. In this manuscript the status of
      the currently available techniques to assess viability was reviewed. Also the
      relative merits of each technique for prediction of functional recovery and
      prognosis was addressed. The available retrospective data support the clinical
      use of viability assessment. Patients with ischemic cardiomyopathy should undergo
      viability testing to determine therapeutic strategy. In the presence of
      substantial amount of viable myocardium, patients should undergo
      revascularization since benefits in terms of left ventricular function,
      remodeling, symptoms and prognosis may be anticipated. However, prospective
      randomized trial are needed to confirm these data.

PMID- 15724139
TI  - Is it time for cardiac innervation imaging?
AB  - The autonomic nervous system plays an important role in the regulation of cardiac
      function and the regional distribution of cardiac nerve terminals can be
      visualized using scintigraphic techniques. The most commonly used tracer is
      iodine-123-metaiodobenzylguanidine (MIBG) but C-11-hydroxyephedrine has also been
      used with PET. When imaging with MIBG, the ratio of heart-to-mediastinal counts
      is used as an index of tracer uptake, and regional distribution is also assessed
      from tomographic images. The rate of clearance of the tracer can also be measured
      and indicates the function of the adrenergic system. Innervation imaging has been
      applied in patients with susceptibility to arrhythmias, coronary artery disease,
      hypertrophic and dilated cardiomyopathy and anthracycline induced cardiotoxicity.
      Abnormal adrenergic innervation or function appear to exist in many
      pathophysiological conditions indicating that sympathetic neurons are very
      susceptible to damage. Abnormal findings in innervation imaging also appear to
      have significant prognostic value especially in patients with cardiomyopathy.
      Recently, it has also been shown that innervation imaging can monitor drug
      induced changes in cardiac adrenergic activity. Although innervation imaging
      holds great promise for clinical use, the method has not received wider clinical
      acceptance. Larger randomized studies are required to confirm the value of
      innervation imaging in various specific indications.

PMID- 15724140
TI  - Molecular imaging. A new approach to nuclear cardiology.
AB  - Nuclear cardiology has historically played an important role in detection of
      cardiovascular disease as well as risk stratification. With the growth of
      molecular biology have come new therapeutic interventions and the requirement for
      new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well
      as transporter gene imaging strategies are evolving to meet these new needs, but
      require the development of an interdisciplinary approach which focuses on
      molecular processes, as well as the pathogenesis and progression of disease. This
      progress has been made possible with the availability of transgenic animal models
      along with many technological advances. Future adaptations of the developing
      experimental procedures and instrumentation will allow for the smooth translation
      and application to clinical practice. This review is intended as a brief overview
      on the subject molecular imaging. Basic concepts and historical perspective of
      molecular imaging will be reviewed first, followed by description of current
      technology, and concluding with current applications in cardiology. The emphasis
      will be on the use of both single photon emission computed tomography (SPECT) and
      positron emission tomography (PET) radiotracers, although other imaging
      modalities will be also briefly discussed. The specific approaches presented here
      will include receptor-based and reporter gene imaging of natural and therapeutic
      angiogenesis.

PMID- 15724141
TI  - The effects of physical activity and body mass index on cardiovascular, cancer
      and all-cause mortality among 47 212 middle-aged Finnish men and women.
AB  - OBJECTIVE: To examine the association of physical activity and body mass index
      (BMI), and their combined effect, with the risk of total, cardiovascular disease
      (CVD) and cancer mortality. DESIGN: Prospective follow-up study. SUBJECTS: In
      all, 22 528 men and 24 684 women aged 25-64 y at baseline having 7394 deaths
      during a mean follow-up of 17.7 y. MEASUREMENT: A self-administered questionnaire
      data on smoking, socioeconomic factors, physical activity and medical history,
      together with measured height, weight, blood pressure and serum cholesterol using
      standardized protocol. RESULT: Physically active subjects had significantly lower
      age-adjusted mortality from cardiovascular, cancer and all causes compared with
      sedentary ones. Further adjustment for smoking, systolic blood pressure,
      cholesterol, BMI, diabetes and education affected the results only slightly.
      Obese subjects (BMI> or =30 kg/m(2)) had significantly higher cardiovascular and
      total mortality than the normal weight (18.5< or =BMI<25 kg/m(2)) subjects. Part
      of increased mortality among obese subjects was mediated through obesity-related
      cardiovascular risk factors. BMI had an inverse association with cancer mortality
      among men and almost significant direct association among women. Total mortality
      was also increased among the lean (BMI<18.5 kg/m(2)) subjects. However, less than
      0.3% of deaths were attributed to low body weight, whereas in men 5.5% and in
      women 17.7% of deaths were attributed to obesity. CONCLUSION: Regular physical
      activity and normal weight are both important indicators for a decreased risk of
      mortality from all causes, CVD and cancer. Physical activity had a strong
      independent effect on mortality, whereas the effect of BMI was partly mediated
      through other obesity-related risk factors.

PMID- 15724142
TI  - Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter
      volumes in a sample of subjects with attention deficit hyperactivity disorder,
      their unaffected siblings, and controls.
AB  - Genetic influences on behavior are complex and, as such, the effect of any single
      gene is likely to be modest. Neuroimaging measures may serve as a biological
      intermediate phenotype to investigate the effect of genes on human behavior. In
      particular, it is possible to constrain investigations by prior knowledge of gene
      characteristics and by including samples of subjects where the distribution of
      phenotypic variance is both wide and under heritable influences. Here, we use
      this approach to show a dissociation between the effects of two dopamine genes
      that are differentially expressed in the brain. We show that the DAT1 gene, a
      gene expressed predominantly in the basal ganglia, preferentially influences
      caudate volume, whereas the DRD4 gene, a gene expressed predominantly in the
      prefrontal cortex, preferentially influences prefrontal gray matter volume in a
      sample of subjects including subjects with ADHD, their unaffected siblings, and
      healthy controls. This demonstrates that, by constraining our investigations by
      prior knowledge of gene expression, including samples in which the distribution
      of phenotypic variance is wide and under heritable influences, and by using
      intermediate phenotypes, such as neuroimaging, we may begin to map out the
      pathways by which genes influence behavior.

PMID- 15724143
TI  - Supraphysiological doses of levothyroxine alter regional cerebral metabolism and
      improve mood in bipolar depression.
AB  - Supplementation of standard treatment with high-dose levothyroxine (L-T(4)) is a
      novel approach for treatment-refractory bipolar disorders. This study tested for
      effects on brain function associated with mood alterations in bipolar depressed
      patients receiving high-dose L-T(4) treatment adjunctive to ongoing medication
      (antidepressants and mood stabilizers). Regional activity and whole-brain
      analyses were assessed with positron emission tomography and
      [(18)F]fluorodeoxyglucose in 10 euthyroid depressed women with bipolar disorder,
      before and after 7 weeks of open-label adjunctive treatment with
      supraphysiological doses of L-T(4) (mean dose 320 microg/day). Corresponding
      measurements were acquired in an age-matched comparison group of 10 healthy women
      without L-T(4) treatment. The primary biological measures were relative regional
      activity (with relative brain radioactivity taken as a surrogate index of glucose
      metabolism) in preselected brain regions and neuroendocrine markers of thyroid
      function. Treatment-associated changes in regional activity (relative to global
      activity) were tested against clinical response. Before L-T(4) treatment, the
      patients exhibited significantly higher activity in the right subgenual cingulate
      cortex, left thalamus, medial temporal lobe (right amygdala, right hippocampus),
      right ventral striatum, and cerebellar vermis; and had lower relative activity in
      the middle frontal gyri bilaterally. Significant behavioral and cerebral
      metabolic effects accompanied changes in thyroid hormone status. L-T(4) improved
      mood (remission in seven patients; partial response in three); and decreased
      relative activity in the right subgenual cingulate cortex, left thalamus, right
      amygdala, right hippocampus, right dorsal and ventral striatum, and cerebellar
      vermis. The decrease in relative activity of the left thalamus, left amygdala,
      left hippocampus, and left ventral striatum was significantly correlated with
      reduction in depression scores. Results of the whole-brain analyses were
      generally consistent with the volume of interest results. We conclude that
      bipolar depressed patients have abnormal function in prefrontal and limbic brain
      areas. L-T(4) may improve mood by affecting circuits involving these areas, which
      have been previously implicated in affective disorders.

PMID- 15724144
TI  - The emerging role of the PI3-K-Akt pathway in prostate cancer progression.
AB  - The PI3-K-Akt pathway plays a central role in the development and progression of
      prostate cancer and other malignancies. We review original studies and summarize
      relevant sections of previous reviews concerning the relationships between
      abnormalities in the PI3-K-Akt pathway and prostate cancer progression. We
      discuss laboratory and clinical data that indicate gene perturbation and
      dysregulation of PI3-K-Akt pathway is common in prostate cancer and other
      malignancies. We further discuss the critical role of the PI3-K-Akt pathway in
      the oncogenic signaling network and provide examples that establish the PI3-K-Akt
      pathway as a focal point for the future development of informative biomarkers and
      effective therapies for prostate cancer.

PMID- 15724145
TI  - Spinal shock revisited: a four-phase model.

PMID- 15724146
TI  - Mapping and verification of susceptibility loci for smoking quantity using
      permutation linkage analysis.
AB  - Nicotine dependence is the most prevalent form of drug addiction in the US and
      throughout the world. Epidemiological studies demonstrate that genetics accounts
      for at least 50% of the liability to nicotine dependence. However, there have
      been very limited linkage studies providing convincing evidence of susceptibility
      genomic loci for this disorder. In this study, we conducted genome-wide
      permutation linkage analyses on the smoking data collected between 1970 and 1972
      of the Framingham Heart Study (FHS) to account for the abnormality associated
      with the smoking quantity (defined as the number of cigarettes smoked per day).
      We used empirical thresholds obtained from permutation tests to determine the
      significance of each genomic region. The variance component method implemented in
      SOLAR was used for the analysis. Under the empirical genome-wide thresholds
      determined specifically for the FHS smoking data, we found two highly or near
      highly significant linkages of nicotine dependence on chromosomes 1 and 4
      (P=0.001) and eight significant linkages on chromosomes 3, 7, 8, 9, 11, 16, 17,
      and 20 (P<0.05). These findings strongly indicate that some of these regions may
      harbor susceptibility loci for nicotine dependence. Further analysis of these
      positive regions by fine mapping and/or association analysis is warranted. To our
      knowledge, this study presents the most convincing linkage evidence for nicotine
      dependence in the field.

PMID- 15724147
TI  - A quantitative genomic expression analysis platform for multiplexed in vitro
      prediction of drug action.
AB  - Genomic expression signatures provide high-content biomarkers of cellular
      physiology, including the diverse responses to therapeutic drugs. To recognize
      these signatures, we devised a method of biomarker evaluation called 'sampling
      over gene space' (SOGS) that imparts superior predictive performance to existing
      supervised classification algorithms. Applied to microarray data from drug
      treated human cortical neuron 1A cell cultures, this method predicts whether
      individual compounds possess anticonvulsant, antihypertensive, cyclooxygenase
      inhibitor, or opioid action. Thus, stable cell lines can be suitable for
      expression signature-based screening of a diverse range of activities. A SOGS
      based system also discriminates physiologically active from inactive compounds,
      identifies drugs with off-target side effects, and incorporates a quantitative
      method for assigning confidence to individual predictions that, at its most
      stringent, approaches 100% accuracy. The capacity to resolve multiple distinct
      drug activities while simultaneously discriminating inactive and potential false
      positive compounds in a cell line presents a unified framework for streamlined
      chemical genomic drug discovery.

PMID- 15724148
TI  - Encoding social signals in the mouse main olfactory bulb.
AB  - Mammalian urine releases complex mixtures of volatile compounds that are used in
      reproduction, territoriality and conspecific recognition. To understand how such
      complex mixtures are represented in the main olfactory bulb, we analysed the
      electrophysiological responses of individual mitral cells to volatile compounds
      in mouse urine. In both males and females, urine volatile compounds evoke robust
      responses in a small subset of mitral cells. Fractionation of the volatile
      compounds using gas chromatography showed that out of the hundreds of compounds
      present, mitral cells are activated by single compounds. One cohort of mitral
      cells responded exclusively to male urine; these neurons were activated by
      (methylthio)methanethiol, a potent, previously unknown semiochemical present only
      in male urine. When added to urine, synthetic (methylthio)methanethiol
      significantly enhances urine attractiveness to female mice. We conclude that
      mitral cells represent natural odorant stimuli by acting as selective feature
      detectors, and that their activation is largely independent of the presence of
      other components in the olfactory stimulus.

PMID- 15724149
TI  - Leptin regulation of bone resorption by the sympathetic nervous system and CART.
AB  - Bone remodelling, the mechanism by which vertebrates regulate bone mass,
      comprises two phases, namely resorption by osteoclasts and formation by
      osteoblasts; osteoblasts are multifunctional cells also controlling osteoclast
      differentiation. Sympathetic signalling via beta2-adrenergic receptors (Adrb2)
      present on osteoblasts controls bone formation downstream of leptin. Here we
      show, by analysing Adrb2-deficient mice, that the sympathetic nervous system
      favours bone resorption by increasing expression in osteoblast progenitor cells
      of the osteoclast differentiation factor Rankl. This sympathetic function
      requires phosphorylation (by protein kinase A) of ATF4, a cell-specific CREB
      related transcription factor essential for osteoblast differentiation and
      function. That bone resorption cannot increase in gonadectomized Adrb2-deficient
      mice highlights the biological importance of this regulation, but also contrasts
      sharply with the increase in bone resorption characterizing another hypogonadic
      mouse with low sympathetic tone, the ob/ob mouse. This discrepancy is explained,
      in part, by the fact that CART ('cocaine amphetamine regulated transcript'), a
      neuropeptide whose expression is controlled by leptin and nearly abolished in
      ob/ob mice, inhibits bone resorption by modulating Rankl expression. Our study
      establishes that leptin-regulated neural pathways control both aspects of bone
      remodelling, and demonstrates that integrity of sympathetic signalling is
      necessary for the increase in bone resorption caused by gonadal failure.

PMID- 15724150
TI  - Agonist/endogenous peptide-MHC heterodimers drive T cell activation and
      sensitivity.
AB  - Alphabeta T lymphocytes are able to detect even a single peptide-major
      histocompatibility complex (MHC) on the surface of an antigen-presenting cell.
      This is despite clear evidence, at least with CD4+ T cells, that monomeric
      ligands are not stimulatory. In an effort to understand how this remarkable
      sensitivity is achieved, we constructed soluble peptide-MHC heterodimers in which
      one peptide is an agonist and the other is one of the large number of endogenous
      peptide-MHCs displayed by presenting cells. We found that some specific
      combinations of these heterodimers can stimulate specific T cells in a CD4
      dependent manner. This activation is severely impaired if the CD4-binding site on
      the agonist ligand is ablated, but the same mutation on an endogenous ligand has
      no effect. These data correlate well with analyses of lipid bilayers and cells
      presenting these ligands, and indicate that the basic unit of helper T cell
      activation is a heterodimer of agonist peptide- and endogenous peptide-MHC
      complexes, stabilized by CD4.

PMID- 15724151
TI  - Fluorescence energy transfer methods in bioanalysis.
AB  - Energy transfer phenomena, in which excited fluorophores transfer energy to
      neighbouring chromophores, are well characterised in photochemistry and have
      found a wide range of applications in analytical biochemistry. The transfer of
      energy from a donor to an acceptor group is only significant over distances of a
      few nm, so it can be used as a spectroscopic ruler and as a means of detecting
      molecular interactions and conformational changes. Such methods usually retain
      the great sensitivity and sample handling flexibility of conventional
      fluorescence techniques. As a result many assays involving enzymes, antibodies
      and nucleotides utilise energy transfer measurement principles. This article
      outlines these principles for the main types of energy transfer, and summarises
      some of their most important areas of application.

PMID- 15724152
TI  - Pharmaceutical counterfeiting.
AB  - Pharmaceutical counterfeiting is becoming a serious problem both in developed and
      developing countries. This paper considers the extent of the problem and provides
      several examples of drugs which have been counterfeited. Additionally, the
      effects of counterfeit products on consumers, health care providers, drug
      manufacturers and governments are discussed. Several of the currently used
      methods of detection are described and these include near-infrared spectroscopy,
      Raman spectroscopy, isotopic characterization, tensiography, chromatographic and
      mass spectrometric approaches. Finally, anti-counterfeiting measures such as the
      use of holograms, tracers and taggants and electronic tracking are summarized.

PMID- 15724153
TI  - Exploration of gas sensing possibilities with edge plane pyrolytic graphite
      electrodes: nitrogen dioxide detection.
AB  - The voltammetric response of nitrogen dioxide in aqueous sulfuric acid using an
      edge plane pyrolytic graphite electrode has been explored and contrasted with
      that from basal plane pyrolytic graphite, glassy carbon or boron-doped diamond
      electrodes. Edge plane graphite electrode is found to produce an excellent
      voltammetric signal in comparison with other carbon-based electrodes exhibiting a
      well-defined analytically useful voltammetric redox couple in 2.5 M sulfuric acid
      which is absent on the alternative electrodes.

PMID- 15724154
TI  - A sensitive method for the detection of proteins by high-efficiency fluorescence
      quenching.
AB  - A successful method for the detection of electron transfer proteins such as
      cytochrome c, hemoglobin and myoglobin has been developed based on the
      fluorescence quenching of semiconductor nanocrystals. High sensitivity and a good
      linear relationship are obtained.

PMID- 15724156
TI  - An easily integrative and efficient micromixer and its application to the
      spectroscopic detection of glucose-catalyst reactions.
AB  - The focus of this paper is on the fabrication of a PDMS-based passive efficient
      micromixer to be easily integrated into the other on-chip microfluidic system.
      The mixing is achieved by "strong stretching and folding," which employs a three
      dimensional microchannel structure. By the simultaneously vertical and
      transversal dispersion of fluids, strong advection is developed. Owing to this
      powerful mixing performance (more than 70% of the mixing is accomplished within
      2.3 mm over a wide range of Reynold number (Re)), the smaller integrative mixer
      can be realized. The feasibility and the potential usefulness of an integrative
      micromixer were evaluated by incorporating two mixers into the microchannel for
      the spectroscopic detection of a glucose-catalyst reaction. The results
      demonstrate a promising performance for diverse applications in the assay or
      synthesis of biological or chemical materials.

PMID- 15724157
TI  - Novel approach for mono-segmented flow micro-titration with sequential injection
      using a lab-on-valve system: a model study for the assay of acidity in fruit
      juices.
AB  - A new concept for micro-titration using a "lab-on-valve"(LOV) system with
      sequential injection of mono-segmented flow is proposed. The performance of the
      system was demonstrated by the assay of acidity in fruit juices which is based on
      acid-base neutralization. A standard/sample solution containing citric acid,
      indicator, sodium hydroxide, were sandwiched between air segments and were
      aspirated in microliter volumes through a selection valve into a holding coil.
      The acid, indicator, and base were mixed by flow reversal. After removing air
      segments, the solution was pushed to the detector for monitoring of the change in
      absorbance of the indicator color, which depended on the concentration of the
      remaining base. With LOV, microliter volumes of the solution can be detected
      without dispersion of the color zone. A calibration graph (plot of absorbance vs.
      acidity value) in the range of 0.2-1.2% (w/v) as citric acid was established.
      Sample throughput of 30 sample h(-1) and good reproducibility (RSD = 1.2%, n= 11
      for 0.6% acidity) were achieved. The procedure has been applied to determine
      acidity in fruit juices.

PMID- 15724158
TI  - Immobilization of individual cells by local photo-polymerization on a chip.
AB  - A novel separation method for random screening of target cells from a large
      heterogeneous population by using a local photo-polymerization is developed. A
      photo-crosslinkable resin solution is mixed with the sample liquid and we
      controlled the state from sol to gel by irradiating the near ultraviolet (UV)
      light with the mercury lamp and He-Cd laser near the target cell. We applied
      three types of immobilization methods such as direct immobilization method,
      caging method, and direct immobilization with position control method. The
      selected cell is immobilized in the cured resin directly or inside the cage of
      the cured resin. In the position control method, laser tweezers are employed to
      manipulate the target cell indirectly by using the droplet of the resin as a
      microtool. The cell is positioned properly by the laser manipulation system and
      is immobilized in the polymerized resin. After the selected cells are immobilized
      we can easily remove the other objects by the cleaning flow in the microchannel
      since the polymerized resin strongly binds with the cover glass and resists more
      than 466 mm s(-1) flow speed in the microchannel (microchannel size: width is 500
      micron and depth is 100 micron). We tested the mercury lamp as well as the He-Cd
      laser for UV-light irradiation at the local area and confirmed improvement of
      resolution of the cured area by using the He-Cd laser (from 7 micron to 5
      micron). Based on this method, we succeeded in single cell immobilization and
      basic experiments such as culture and fluorescent dyeing of immobilized yeast
      cells.

PMID- 15724159
TI  - Single-cell growth and division dynamics showing epigenetic correlations.
AB  - The emergence of variation and subsequent inheritance of the emergent
      characteristics in a clonal population of bacteria is considered as evidence for
      epigenetic processes in the cell. We report here the results of experiments in
      which we quantitatively examined variations in single Escherichia coli cells with
      an identical genetic endowment in order to establish whether certain
      characteristics of single cells were inherited by their descendants maintained in
      a uniform environment. Significantly large variations of interdivision time,
      initial length, and final length were observed from generation to generation.
      Comparing the generations shows that interdivision time had no correlation with
      that of the consecutive generations, whereas those of initial length and final
      length were positively correlated with those of neighbouring generations.

PMID- 15724160
TI  - Isolation of naturally occurring aluminium ligands using immobilized metal
      affinity chromatography for analysis by ESI-MS.
AB  - Aluminium (iii) is one of the most abundant metal ions found in soil. Typically,
      Al(+3) is bound to minerals, but its bioavailability and toxicity toward vascular
      plants increases with increasing soil acidity. Ectomycorrhizal fungi, which live
      symbiotically on the roots of numerous woody plants, often confer Al(+3)
      resistance to host plants by reducing metal availability to the plant by unknown
      mechanisms. A potential mechanism of detoxification is binding of the Al(+3) by
      organic compounds that are exuded by the fungi into the surrounding soil and
      solution. A novel method has been developed to purify and characterize Al(+3)
      binding ligands from Pisolithus tinctorius exudate solutions using Al(+3)
      immobilized metal affinity chromatography (IMAC), reversed phase chromatography,
      and mass spectrometry. Fungal exudates produced by P. tinctorius exhibit a strong
      binding capacity for Al(+3), allowing their selective enrichment and collection
      using this IMAC method. Elution of the ligands requires the use of high pH. RP
      HPLC separation and elemental analysis of the IMAC elutent indicates that the
      Al(+3) and the exudate ligands both elute from the column but are not bound in a
      complex. Thus, reversed phase HPLC at pH 10 is used for separation of the ligands
      and Al(+3) prior to MS analysis. The strongest binding IMAC fraction is analyzed
      by electrospray ionization mass spectrometry in positive and negative ion modes.
      This report provides new methods for the direct purification and analysis of
      naturally occurring ligands that bind hard metal ions.

PMID- 15724161
TI  - Detection of fortification of ginkgo products using nanoelectrospray ionization
      mass spectrometry.
AB  - We report here a negative ionization nanoelectrospray ionization mass
      spectrometry (nanoESI-MS) technique that simultaneously detects active
      components, terpenes and intact flavonol glycosides, and toxic ginkgolic acids in
      ginkgo products. Unlike the conventional methods that hydrolyze flavonol
      glycosides to flavonoids for analysis, this technique directly detects intact
      flavonol glycosides, enabling differentiation of these natural glycosides from
      the synthetic flavonoids. Thus, it allows the detection of fortification of
      ginkgo products, alleviating a common problem encountered by the conventional
      methods. Analysis of 14 commercial ginkgo products using this technique
      demonstrates large variations and deviation from the well-accepted standardized
      ginkgo extract. Four products showed evidence of fortification with synthetic
      surrogates. Two products were found to have toxic ginkgolic acids that exceed the
      5 microg g(-1) limit by as much as 60000 fold. These results emphasize the
      importance of appropriate monitoring of ginkgo product quality.

PMID- 15724162
TI  - Analytical chemistry of synthetic routes to psychoactive tryptamines. Part II.
      Characterisation of the Speeter and Anthony synthetic route to N,N-dialkylated
      tryptamines using GC-EI-ITMS, ESI-TQ-MS-MS and NMR.
AB  - The degree of alkylation of the side chain nitrogen in tryptamines is one
      important factor that affects psychoactivity. The method of Speeter and Anthony
      is considered to be one of the most important synthetic preparative methods. The
      final step in this reaction is based on the reduction of a (substituted) indole-3
      yl-glyoxalylamide to the desired tryptamine with metal hydride. Twelve
      symmetrically and 13 asymmetrically N,N-disubstituted glyoxalylamides and their
      corresponding tryptamine derivatives have been synthesised and characterised by
      gas chromatography EI-ion trap mass spectrometry, electrospray-triple quadrupole
      tandem mass spectrometry and NMR spectroscopy. Mass spectral and NMR similarities
      and differences between the investigated compounds are discussed. A solvent
      dependency is observed that has to be taken into consideration for the
      unambiguous assignment of (1)H- and (13)C-NMR chemical shifts. The (1)H-NMR study
      demonstrated that one can evaluate the rotamer populations of the asymmetrical
      glyoxalylamides. In a forensic or clinical scenario where single or multiple
      reaction monitoring approaches are contemplated, the appropriate ion transitions
      of choice may then focus on the two main fragmentations, namely beta-cleavage
      ([M+H](+)-->CH(2)N(+)R(2)R(3)) and/or alpha-cleavage ([M+H](+)-->[3
      vinylindole](+)), respectively. The synthesis, NMR and MS analytical data
      presented provide the forensic analyst and clinical biochemist with a detailed
      and self-consistent body of information and mechanisms for the spectral
      identification of the more likely psychoactive tryptamines that may be met.

PMID- 15724163
TI  - Tethered DNA hairpins facilitate electrochemical detection of DNA ligation.
AB  - A novel electrochemical assay for DNA ligase activity is described. The assay
      exploits the properties of DNA hairpins tethered at one terminus to a gold
      electrode and labelled at the other with a ferrocene group for rapid
      characterisation of DNA status by cyclic voltammetry. Successful ligation of
      'nicked' DNA hairpins is indicated by retention of the ferrocene couple when
      exposure to DNA ligase is followed by conditions that denature the hairpin. The
      results demonstrate the simplicity of integrating electrochemical detection with
      hairpin based biosensors and illustrate a new approach to the assay of DNA
      ligases, of which the NAD(+)-dependent enzymes represent a potential broad
      spectrum antibacterial drug target.

PMID- 15724164
TI  - Using molecular beacon to monitor activity of E. coli DNA ligase.
AB  - NAD(+)-dependent DNA ligase has been widely used in gene diagnostics for disease
      associated mutation detection and has proved to be necessary for screening
      bactericidal drugs targeted to DNA ligases. However, further research has been
      restricted since conventional ligase assay technology is limited to gel
      electrophoresis, which is discontinuous, time-consuming and laborious. An
      innovative approach is developed for monitoring the activity of E. coli DNA
      ligase catalyzing nucleic acid ligation in the report. This approach utilizes a
      molecular beacon hybridized with two single-stranded DNA (ssDNA) segments to be
      ligated to form a hybrid with a nick, and could therefore be recognized by the
      enzyme. Ligation of the two ssDNA segments would cause conformation changes of
      the molecular beacon, leading to significant fluorescence enhancement. Compared
      to gel electrophoresis, this approach can provide real time information about
      ligase, is more time efficient, and is easier to use. The effect of quinacrine, a
      drug for malaria, on the activity of the ligase is detected, thereby certifying
      the capability of the method for developing novel antibacterial drugs targeted at
      NAD(+)-dependent ligase. The fidelity of strand joining by the ligase is examined
      based on this approach. The effects of external factors on activity of the ligase
      are analyzed, and then an assay of E. coli DNA ligase is performed with a broad
      linear range of 4.0 x 10(-4) Weiss Unit mL(-1) to 0.4 Weiss Unit mL(-1) and the
      detection limit of 4.0 x 10(-4) Weiss Unit mL(-1).

PMID- 15724166
TI  - Effects of gold nanoparticle and electrode surface properties on electrocatalytic
      silver deposition for electrochemical DNA hybridization detection.
AB  - In this paper we report the catalytic effects of various gold nanoparticles for
      silver electrodeposition on indium tin oxide (ITO)-based electrodes, and
      successfully apply this methodology for signal amplification of the hybridization
      assay. The most widely used gold nanoparticle-based hybridization indicators all
      promote silver electrodeposition on the bare ITO electrodes, with decreasing
      catalytic capability in order of 10 nm gold, DNA probe-10 nm gold conjugate,
      streptavidin-5 nm gold, and streptavidin-10 nm gold. Of greater importance, these
      electrocatalytic characteristics are affected by any surface modifications of the
      electrode surfaces. This is illustrated by coating the ITO with an
      electroconducting polymer, poly(2-aminobenzoic acid)(PABA), as well as avidin
      molecules, which are promising immobilization platforms for DNA biosensors. The
      catalytic silver electrodeposition of the gold nanoparticles on the PABA-coated
      ITO surfaces resembles that on the bare surfaces. With avidin covalently bound to
      the PABA, it is interesting to note that the changes in electrocatalytic
      performance vary for different types of gold nanoparticles. For the streptavidin
      5 nm gold, the silver electrodeposition profile is unaffected by the presence of
      the avidin layer, whereas for both the 10 nm Au and DNA probe-10 nm gold
      conjugate, the deposition profiles are suppressed. The streptavidin-5 nm gold is
      employed as the hybridization indicator, with avidin-modified (via PABA) ITO
      electrode as the immobilization platform, to enable signal amplification by the
      silver electrodeposition process. Under the conditions, this detection strategy
      offers a signal-to-noise ratio of 20. We believe that this protocol has great
      potential for simple, reproducible, highly selective and sensitive DNA detection
      on fully integrated microdevices in clinical diagnostics and environmental
      monitoring applications.

PMID- 15724167
TI  - Simple algorithms for nonlinear calibration by the classical and standard
      additions methods.
AB  - In univariate calibration by both the classical method and the standard additions
      method, calibration data are fitted to a response function y=f(x), from which the
      amount of an unknown x(0) is estimated by solving an equation of form
      y(0)=f(x(0)). Most such calibrations are limited to linear response functions f,
      for which the uncertainty in x(0) can be estimated from well-known expressions.
      The present work describes and illustrates one-step algorithms, in which x(0) is
      treated as an adjustable parameter in a nonlinear fit of the calibration data,
      with its standard error thus obtained numerically as a direct outcome of the fit.
      The computations are easily implemented with a number of data analysis programs
      and are illustrated here for a representative one, KaleidaGraph. The methods
      handle heteroscedastic data as easily as homoscedastic and nonlinear functions as
      easily as linear, permitting the analyst to experiment with different response
      functions in the quest for an optimum calibration. The estimates of sigma (x0)
      are obtained from the variance-covariance matrix V for the fit, so for weighted
      fitting with commercial programs, it is important to know which V--a priori or a
      posteriori--is being used.

PMID- 15724168
TI  - Near-infrared spectroscopic observation of the ageing process in archaeological
      wood using a deuterium exchange method.
AB  - The ageing degradation of the fine wood structure of dry-exposed archaeological
      wood was investigated by Fourier transform near-infrared spectroscopy with the
      aid of a deuterium exchange method. The archaeological wood sample was taken from
      an old wooden temple in Japan (late 7th century), which has been designated as a
      UNESCO world heritage site. Comparing the analytical results with those of a
      modern wood sample of the same species, the ageing process of archaeological wood
      was clarified as a change in the state of order on a macromolecular structural
      level. It can be concluded from NIR spectra that the amorphous region, and
      partially semi-crystalline region, in cellulose, hemicellulose, and lignin
      decreased by the ageing degradation, whereas the crystalline region in cellulose
      was not affected by the ageing. The accessibility of the diffusant to effect H/D
      exchange was monitored by an OH-related absorption band obtained from FT-NIR
      transmission spectroscopy and characteristically varied with the ageing process
      of the wood samples, the absorption bands characteristic of a specific state of
      order and the diffusion agent. Finally, we proposed a morphological model to
      describe the variation of the fine structure of the microfibrils in the cell wall
      with ageing degradation. The state of microfibrils changed loosely by ageing, so
      that elementary fibrils were arranged loosely under 5 A, whereas several
      elementary fibrils in the modern wood were arranged in very close proximity under
      3 A to each other.

PMID- 15724169
TI  - A novel method for the filterless preconcentration of iron.
AB  - A novel method of analysis of iron by filterless preconcentration is presented.
      This is the first example of efficient preconcentration of a refractory
      transition metal where coprecipitation and columns were omitted. The method
      applies a manifold of flow injection analysis (FIA) to iron species that are
      preconcentrated on the inner walls of a tubular reactor. It was found that the
      adsorption of iron species to the walls was particularly pronounced in reactors
      of nylon material and enrichment factors of 30-35 could be attained, as dependent
      on the length of the reactor and on the time of preconcentration. In the
      preconcentration step of the FIA accessory, the optimum efficacy was obtained
      when the acidity of the samples was adjusted by HCl to pH = 2.5 whereas the
      ammonia preconcentration buffer should be kept alkaline at pH = 9.8. After being
      preconcentrated on the tubular reactor, the iron species were eluted by
      hydrochloric acid and analysed by flame atomic absorption spectrometry (FAAS). An
      unprecedented low limit of detection (LOD, 3sigma) of 1.8 microg L(-1) was thus
      obtained for the analysis of iron by FAAS, and the calibration line was linear up
      to 100 microg L(-1). A high sampling frequency of 40 per hour was obtained and
      the protocol allowed analysis of small amounts of iron in drinking water, in
      digested samples and in saline water. The major influence of interferences
      originated from ligands that are known to complex strongly to iron species. The
      method thus developed was uncomplicated in operation and it exhibited an
      excellent long-term stability and a high selectivity. Further, it was
      environmentally safe owing to production of non-toxic waste disposals. Equally
      high enrichment factors (EF) were obtained for Fe(ii) and Fe(iii), which is
      explained by the very low solubility product of both species.

PMID- 15724170
TI  - Immobilization of DNA on carbon fiber microelectrodes by using overoxidized
      polypyrrole template for selective detection of dopamine and epinephrine in the
      presence of high concentrations of ascorbic acid and uric acid.
AB  - The overoxidized polypyrrole (PPyox) film as a template for DNA immobilization
      has been demonstrated in this paper. The DNA molecules inserted into the
      micropores of the ultrathin PPyox matrix under the driving forces of an electric
      field and were firmly immobilized on the carbon fiber electrode (CFE). Such a DNA
      PPyox biocomposite layer exhibited more effective rejection of anionic ascorbate
      (AA) and uric acid (UA) and more preferential collection of the cationic dopamine
      (DA) and epinephrine (EP) than pure PPyox and DNA coatings. The DPV peak currents
      increased linearly with increasing DA and EP concentrations in the range of 3.0 x
      10(-7) to 1.0 x 10(-5) M and 5.0 x 10(-7) to 2.0 x 10(-5) M with the lowest
      detected concentrations of 8.0 x 10(-8) M and 6.0 x 10(-8) M, respectively. The
      electrochemical signal of AA could be totally suppressed under a concentration of
      20 mM and beyond this concentration, the overlapped responses of AA, DA/EP and UA
      could be resolved into three well-defined voltammetric peaks. The selectivity
      factors k(DA/AA) and k(EP/AA) were about 5000 and 2000 for an equal concentration
      in the presence of 0.5 mM UA. The properties of the biocomposite film have been
      characterized by atomic force microscopy and electrochemical investigations.

PMID- 15724171
TI  - Membrane-introduced infrared spectroscopic chemical sensing method for the
      detection of volatile organic compounds in aqueous solutions.
AB  - A novel membrane-introduced infrared (IR) chemical sensing method has been
      developed for the detection of volatile organic compounds (VOCs) in aqueous
      solutions. In this method, a porous Teflon membrane was used to eliminate the
      problems associated with conventional IR spectroscopic sensing methods. The
      porous Teflon membrane was sealed below an IR spectroscopic sensing element pre
      coated with a hydrophobic film and a two-channel flow cell configuration was
      established. In this configuration, the aqueous sample was allowed to pass
      through the lower channel and the VOCs that penetrated through the membrane to
      the upper channel were detected by the IR sensor. In this manner, the performance
      of the sampling at the headspace was improved while the problems caused by the
      presence of water were eliminated. Meanwhile, using a purging channel allowed the
      sensing element to be regenerated rapidly and enabled automation of the detection
      process. The parameters that influenced the analytical signals were studied, such
      as the sampling flow rate, the pH and ionic strength of the sample solutions, the
      effect of the volatilities of the VOCs, and the regeneration efficiency of the
      sensing element. The results indicated that the analytical signals were
      insensitive to the sampling flow rate and to the pH and ionic strength of the
      sample solutions. The results obtained from the detection of seven different
      volatile compounds indicated that this method is highly suitable for the
      detection of organic compounds that have vapor pressures >1 Torr and that it is
      potentially usable for organic compounds that have vapor pressures between 20
      mTorr and 1 Torr. The regression analysis of the standard curves indicated that a
      regression coefficient (R(2)) > 0.99 was obtainable in the concentration range
      from 1 to 100 microg mL(-1). The detection limits for the tested compounds were
      around a few hundred ng mL(-1).

PMID- 15724172
TI  - Catechol imine ligands: from helicates to supramolecular tetrahedra.
AB  - Di- and tricatechol imines are easily accessible by condensation of appropriate
      amines with 2,3-dihydroxybenzaldehyde. Dicatechol imines can be used for the
      alkali metal template-directed self-assembly of dinuclear triple-stranded
      helicates or meso-helicates with high diastereoselectivity. Tricatechol imines
      lead in self-assembly processes to metallosupramolecular 4 [ratio] 4 tetrahedra
      with a huge internal cavity, which is able to encapsulate guest species. Hereby
      the special features of the imine unit can be used to control the outcome of the
      self-assembly process.

PMID- 15724173
TI  - Hierarchical mesoporous silica wires by confined assembly.
AB  - The assembly of silicate and surfactant confined within cylindrical alumina pore
      channels results in circular hexagonal, concentric lamellar and other unique
      mesostructures.

PMID- 15724174
TI  - "Polar patch" proteases as glycopeptiligases.
AB  - The strategy of combined site directed mutagenesis and chemical modification with
      polar prosthetic groups was used to broaden substrate specificity of proteases
      resulting in the first successful formation of glycopeptides through the use of
      glucoamino acid acyl donors in yields of up to 90%.

PMID- 15724175
TI  - A novel microporous copper silicate: Na2Cu2Si4O11.2H2O.
AB  - The synthesis and structural characterisation of a thermally stable novel three
      dimensional microporous copper silicate open-framework are described; the
      material is capable of undergoing reversible zeolitic water removal without
      destruction of the framework.

PMID- 15724176
TI  - Magnetic field effect on singlet oxygen production in a biochemical system.
AB  - The yield of singlet oxygen sensitized by chemically modified, carotenoidless
      bacterial photosynthetic reaction centres and the ensuing oxidative damage are
      both shown to be magnetic field-dependent.

PMID- 15724178
TI  - Straightforward detection of the secondary ionisation of the phosphate group and
      pK determinations by high-resolution solid-state 31P NMR.
AB  - The suitability of high-resolution solid-state 31P NMR for a straightforward
      determination of the protonation state of phosphate groups as well as of their
      pK2 values extracted from solid state mono : dianionic ratios has been
      demonstrated.

PMID- 15724177
TI  - Promotion of oxygen atom transfer in Mo and W enzymes by bicyclic forms of the
      pterin cofactor.
AB  - Density functional theory calculations suggest that bicyclic structures of the
      "molybdopterin" in DMSO reductases may have an important catalytic role in oxygen
      atom transfer reactions.

PMID- 15724179
TI  - Separation of denatured proteins in free solution on a microchip based on
      differential binding of alkyl sulfates with different carbon chain lengths.
AB  - Denatured proteins were separated in free solution on a microfluidic chip without
      any sieving matrix after carrying out the denaturation with a mixture of alkyl
      sulfates with different carbon chain lengths.

PMID- 15724181
TI  - Highlighting gyroscopic motion in crystals in 13C CPMAS spectra by specific
      isotopic substitution and restricted cross polarization.
AB  - The temperature-dependent exchange rate and signal coalescence in the 13C CPMAS
      NMR spectrum of a crystalline molecular gyroscope are exposed by specifically
      deuterating the overlapping static carbons.

PMID- 15724180
TI  - Equisetin biosynthesis in Fusarium heterosporum.
AB  - An iterative polyketide synthase-peptide synthetase hybrid assembles the HIV-1
      integrase inhibitory tetramic acid, equisetin, in the filamentous fungus Fusarium
      heterosporum.

PMID- 15724182
TI  - Pre-organization induced synthesis of a crossed alkene-bridged nisin Z DE-ring
      mimic by ring-closing metathesis.
AB  - An alkene-bridged mimic of the complex DE-bisthioether-ring system of the
      antibiotic nisin was prepared in one step from the linear precursor.

PMID- 15724183
TI  - A peptide-catalyzed asymmetric Stetter reaction.
AB  - Thiazolylalanine, in appropriately functionalized form, has been found to
      function as an enantioselective catalyst for an intramolecular Stetter reaction.
      Incorporation of the residue in a number of environments has resulted in a family
      of catalysts that promote the cyclization of a test substrate with up to 81%
      enantiomeric excess.

PMID- 15724184
TI  - Highly selective epoxidation of styrene using a transition metal-aluminium(III)
      complex containing the [MeAl(2-py)3]- anion (2-py = 2-pyridyl).
AB  - The reactions of [MeAl(2-py)3Li.thf] (1) with FeCl2 or Cp2Mn in toluene-thf give
      simple access to the Group 13-transition metal heterometallic complexes [{MeAl(2
      py)3}2M][M = Fe (2), Mn (3)]; complex has been shown to be a highly selective
      styrene epoxidation catalyst in air.

PMID- 15724185
TI  - Direct quantitative determination of surface Bronsted acidity of solids by H/D
      exchange using D2O.
AB  - A highly flexible method for direct and quantitative determination of surface
      Bronsted acidity of solids in terms of number, type and strength of the acid
      sites based on quantitative H/D exchange kinetics between the acid solid and
      gaseous D2O has been developed and applied to materials covering the whole range
      of acidity.

PMID- 15724186
TI  - Doped spiral alumina nanowires.
AB  - Spiral alumina nanowires, doped with Cr and Si, are directly and reliably
      produced in bulk quantities via annealing of high entropy alloys.

PMID- 15724187
TI  - A small peptide stereochemically customized as a globular fold with a molecular
      cleft.
AB  - A boat shaped peptide molecular fold is generated by stereochemical modification
      of a 20-residue beta-hairpin peptide, making it a promising prototype for future
      optimization as a molecular receptor.

PMID- 15724188
TI  - Synthesis of siliceous hollow spheres with large mesopore wall structure by
      supercritical CO2-in-water interface templating.
AB  - Hollow silica spheres with large mesopore wall structures have been synthesized
      via CO(2)-in-water emulsion templating in the presence of PEO-PPO-PEO block
      copolymers under supercritical fluid conditions.

PMID- 15724189
TI  - [MoO2Cl2] as catalyst for hydrosilylation of aldehydes and ketones.
AB  - The high valent molybdenum-dioxo complex [MoO2Cl2] catalyzes the addition of
      dimethylphenylsilane to aldehydes and ketones to afford the corresponding
      dimethylphenylsilyl ethers in quantitative yield.

PMID- 15724190
TI  - Double gradient ion chromatography on a short carboxybetaine coated monolithic
      anion exchanger.
AB  - An ultra-short 1.0 x 0.46 cm carboxybetaine coated monolithic anion exchanger has
      been used with a new double gradient ion chromatography (DG-IC) technique. The
      novel monolithic column can be used with flow rate gradients giving excellent
      peak efficiencies, and retention times can be simultaneously reduced through
      combining flow gradients with an eluent pH gradient.

PMID- 15724191
TI  - Unexpected retention of electrostatically adsorbed cytochrome c in high ionic
      strength solutions.
AB  - Redox inactivation, but not removal, of electrostatically adsorbed cytochrome
      c(cyt-c) on an alkanethiol modified gold surface was observed after exposure of
      the electrode to 1.0 M aqueous NaCl, NaClO4, KCl, or KClO4 solutions.

PMID- 15724192
TI  - The first rhodaboratrane: [RhCl(PPh3){B(mt)3}](Rh-->B)(mt = methimazolyl).
AB  - The reaction of [Rh(C6H5)Cl2(PPh3)2] with Na[HB(mt)3](mt = methimazolyl) provides
      [RhCl(PPh3){B(mt)3}](Rh-->B) the first authentic example of a compound with a
      rhodium-boron dative bond.

PMID- 15724193
TI  - A heme-like, water-soluble iron(II) porphyrin: thermal and photoinduced
      properties, evidence for sitting-atop structure.
AB  - Water-soluble ferrous porphyrin (Fe(II)TPPS) was prepared by complexation
      reaction of free base porphyrin (H2TPPS) with iron(II) ions in the presence of
      iron(III)-trapping acetate buffer; the catalytic and photoinduced properties of
      this air-stable complex proved unambiguously its sitting-atop structure.

PMID- 15724194
TI  - Novel amine-catalysed hydroalkoxylation reactions of activated alkenes and
      alkynes.
AB  - Substoichiometric loadings of DBU catalyse the efficient 1,4-addition of alcohols
      and non-nucleophilic amines such as pyrrole to activated alkenes; the application
      of this methodology in a one-pot synthesis of a natural product, and as a novel
      strategy for the synthesis of mono-protected 1,3-carbonyl compounds is reported.

PMID- 15724195
TI  - Boronic acid-substituted metal complexes: versatile building blocks for the
      synthesis of multimetallic assemblies.
AB  - Polypyridyl complexes of Ru(II) and Ir(III) incorporating a boronic acid
      substituent undergo cross-coupling with bromo-substituted complexes, and a
      sequential coupling-bromination-coupling strategy permits the controlled
      synthesis of a luminescent Y-shaped heterometallic assembly, in which efficient
      energy transfer to the terminus occurs.

PMID- 15724196
TI  - A novel high-spin heterometallic Ni12K4 cluster incorporating large Ni-azide
      circles and an in situ cyanomethylated di-2-pyridyl ketone.
AB  - Reaction of di-2-pyridyl ketone (dpk) with nickel acetate and azide in the
      presence of potassium tert-butylate as a catalytic base generates the title
      compound, which contains the largest [Ni(mu(1,1)-N3)]6 circles in the discrete
      ferromagnetically-coupled M(II)-azide cluster family, and shows an unprecedented
      in situ cyanomethylation of ketone.

PMID- 15724197
TI  - Indolocarbazoles: a new family of anion sensors.
AB  - Simple preorganised indolo[2,3-a]carbazole derivatives are shown to recognise and
      sense anionic guest species using fluorescence spectroscopy.

PMID- 15724198
TI  - A new class of long-wavelength fluorophores: strong red fluorescence, convenient
      synthesis and easy derivation.
AB  - A new class of structurally simple fluorophores with strong long-wavelength
      emission have been developed through a very convenient procedure.

PMID- 15724199
TI  - A novel method for synthesizing EuS nanocrystals from a single-source precursor
      under white LED irradiation.
AB  - EuS nanocrystals, with an average diameter of 9 nm, have been synthesized by the
      photolysis of Na[Eu(S2CEt2)4].3.5H2O; the first quantum confined particles of EuS
      to be reported.

PMID- 15724200
TI  - Cell-permeable GPNA with appropriate backbone stereochemistry and spacing binds
      sequence-specifically to RNA.
AB  - Guanidine-based peptide nucleic acid (GPNA) with a d-backbone configuration and
      alternate spacing binds sequence-specifically to RNA and is readily taken up by
      both human somatic and embryonic stem (ES) cells.

PMID- 15724201
TI  - The closo-Pb10(2-) Zintl ion in the [Ni@Pb10]2- cluster.
AB  - The cluster [Ni@Pb10](2-), prepared from Pb9(4-) and Ni(COD)2, contains a new
      Zintl ion subunit, closo-Pb10(2-), centered by a Ni atom.

PMID- 15724202
TI  - Notable deuterium effect on the electron transfer rate of myoglobin.
AB  - The electron transfer reaction of wild-type myoglobin at an electrode was
      significantly facilitated in a D2O buffer as compared with that in an H2O buffer,
      with k(0)'(H2O)/k(0)'(D2O)= 0.13, while a minimal deuterium kinetic isotope
      effect on the myoglobin with modification at distal histidine (His-64) was
      observed.

PMID- 15724203
TI  - Anaerobic oxidation of non-activated secondary alcohols over Cu/Al2O3.
AB  - A liquid phase, transfer dehydrogenation reaction promoted by an 8% Cu/Al(2)O(3)
      catalyst allows complete conversion of secondary alcohols into ketones under very
      mild conditions and in short times without any additives.

PMID- 15724204
TI  - Assembly modulates dissociation: electrokinetic experiments reveal peculiarities
      of the charge formation at monolayer films.
AB  - Self-assembled monomolecular films of alkanethiols chemisorbed on gold were used
      as a two-dimensional model system to study the effects of spatial confinement of
      surface functional groups on their acid-base behaviour; reduction of the surface
      charge density by mixed assemblies revealed an increase of the acidity of carboxy
      groups; surfaces with low amounts of charged groups show the interplay of
      dissociation of functional groups and preferential adsorption of ions in terms of
      surface charge formation.

PMID- 15724205
TI  - pH dependent self-assembly of dimetallic lanthanide complexes.
AB  - pH dependent self-association has been observed in a series of DO3A-derived
      lanthanide complexes bearing a carboxylate group that can act as a bridging
      ligand at high pH, switching on the luminescence from the lanthanide.

PMID- 15724206
TI  - Novel alpha-functionally substituted amino acids: diphenylphosphinoglycines.
AB  - The three-component one-pot reaction of glyoxalic acid hydrate with P-H and N-H
      compounds allows a convenient access to phosphinoglycines. The molecular
      structure of , determined by X-ray crystallography, some reactions and an
      alternative formation of phosphinoglycolates are reported.

PMID- 15724207
TI  - Evidence for a hydrogen abstraction mechanism in P450-catalyzed N-dealkylations.
AB  - The experimental evidence presented in this manuscript suggest against the widely
      accepted single electron/proton transfer mechanism for P450 catalyzed N
      dealkylations and provides strong support for a hydrogen atom abstraction
      mechanism.

PMID- 15724208
TI  - Highly active meso-microporous TaON photocatalyst driven by visible light.
AB  - TaON was found to be ca. 20 times more active as a visible light activated
      photocatalyst for the oxidation of methanol, when compared to the well studied UV
      visible activated TiO2 (P25) catalyst.

PMID- 15724209
TI  - Sequential homobimetallic catalysis: an unprecedented tandem Pd(0)-catalysed
      deprotection - Pd(II)-catalysed heterocyclisation reaction leading to
      benzofurans.
AB  - We report here the first example of "sequential homobimetallic catalysis": a
      transition metal catalyst with the metal in a certain oxidation state catalyses
      the deprotection of a functional group, which in situ undergoes a subsequent
      transformation catalysed by another complex of the same metal but in a different
      oxidation state.

PMID- 15724210
TI  - Versatile functionalization and grafting of poly(epsilon-caprolactone) by Michael
      type addition.
AB  - The Michael-type addition of aliphatic (co)polyesters onto gamma-acryloyloxy
      epsilon-caprolactone units is a very straightforward technique of
      functionalization and grafting, which is tolerant to a variety of functional
      groups and does not require intermediate protection/deprotection steps.

PMID- 15724211
TI  - Formation of helical superstructures from a semi-fluorinated alkoxysilane through
      a surface and solution self-assembly process.
AB  - Helical superstructures were obtained through a surface and solution self
      assembly process when a semi-fluorinated alkoxysilane modified silicon wafer was
      immersed in water of pH values ranging from 5.0 to 7.0 for more than one month.

PMID- 15724212
TI  - Highly selective Ba2+ separations with acyclic, lipophilic di-[N-(X)sulfonyl
      carbamoyl] polyethers.
AB  - New lipophilic acyclic polyethers with two N-(X)sulfonyl carbamoyl groups of
      "tunable" acidity exhibit remarkable selectivity for Ba2+ over other alkaline
      earth metal ions in competitive solvent extraction and transport across polymer
      inclusion membranes.

PMID- 15724213
TI  - The two-step chemical vapor deposition of Pd(allyl)Cp as an atom-efficient route
      to synthesize highly dispersed palladium nanoparticles on carbon nanofibers.
AB  - Highly dispersed palladium nanoparticles supported on carbon nanofibers, which
      show high catalytic activity and stability in the hydrogenation of cyclooctene,
      were synthesized by the two-step metal organic chemical vapor deposition (MOCVD)
      of allylcyclopentadienylpalladium (Pd(allyl)Cp) as precursor at atmospheric
      pressure.

PMID- 15724215
TI  - Natural polysaccharides as electroactive polymers.
AB  - Electroactive polymers (EAPs), a new class of materials, have the potential to be
      used for applications like biosensors, environmentally sensitive membranes,
      artificial muscles, actuators, corrosion protection, electronic shielding, visual
      displays, solar materials, and components in high-energy batteries. The
      commercialization of synthetic EAPs, however, has so far been severely limited.
      Biological polymers offer a degree of functionality not available in most
      synthetic EAPs. Carbohydrate polymers are produced with great frequency in
      nature. Starch, cellulose, and chitin are some of the most abundant natural
      polymers on earth. Biopolymers are a renewable resource and have a wide range of
      uses in nature, functioning as energy storage, transport, signaling, and
      structural components. In general, electroactive materials with polysaccharide
      matrices reach conductance levels comparable with synthetic ion-conducting EAPs.
      This review gives a brief history of EAPs, including terminology, describes
      evaluation methods, and reports on the current progress of incorporating
      polysaccharides as matrices for doped, blended, and grafted electroactive
      materials.

PMID- 15724214
TI  - Isolation and characterization of a fruiting body-specific exo-beta-1,3-glucanase
      encoding gene, exg1, from Lentinula edodes.
AB  - An exo-beta-1,3-glucanase-encoding gene was isolated from Lentinula edodes to
      investigate the relationship between the cell wall lytic enzyme and mushroom
      morphogenesis. The deduced amino acid sequence of the protein corresponding to
      the exg1 gene displayed 67% identity to AbEXG1 of Agaricus bisporus and
      approximately 40% identity to yeast exo-beta-1,3-glucanases. Two conserved
      glutamic acids within the catalytic active site in yeast exo-beta-1,3-glucanases
      were conserved in exg1 of L. edodes. The exg1 gene was expressed in fruiting
      bodies, but not in vegetative mycelia. Expression was higher in the stipe than in
      the pileus of young fruiting bodies. The gene was additionally expressed in the
      gills of mature fruiting bodies. We purified a glucanase from the stipes of young
      fruiting bodies that had an N-terminus identical to that of the putative exg1
      product. These results collectively indicate that exg1 is involved in L. edodes
      fruiting body development, including stipe elongation.

PMID- 15724216
TI  - [Passive smoking--the damage begins in the womb].

PMID- 15724217
TI  - [NSCLC--radiotherapy as an alternative to surgery].

PMID- 15724218
TI  - [Asthma therapy--individual patient plans with few emergency occurrences are the
      best].

PMID- 15724219
TI  - [Asthma--prevention of glucocorticoid-induced osteoporosis with etidronate and
      calcium].

PMID- 15724220
TI  - [Pulmonary hypertension--complications after pulmonary embolism].

PMID- 15724221
TI  - [Disease management program for asthma and COPD -- a step forward or backward?].

PMID- 15724222
TI  - [Asbestos -- the never ending story?].

PMID- 15724223
TI  - [Efficacy of a disease management programme in asthma].
AB  - BACKGROUND: Disease Management Programmes (DMP) are intended to improve the
      quality of the medical care of chronically sick patients and at the same time to
      keep stable or to reduce the costs to the healthcare system. The effectiveness of
      a DMP was evaluated by means of an accompanying study. METHOD: Within the
      framework of the DMP, the patients were managed by case managers who carried out
      patient instructions, evaluated the symptoms and lung function values (FEV (1))
      on a daily basis and supervised treatment goals with the aid of predetermined
      algorithms. Initially, in collaboration with the family doctor, a treatment
      schedule was drawn up continuously monitored and adapted. In a 12-month
      multicentre evaluation study, the quality of life of the patients was determined
      using the FLA and Euroquol questionnaires. Furthermore, symptoms, lung function
      (FEV (1)) and the total costs of the treatment were measured. RESULTS: The
      quality of life (FLA, EuroQuol) of the patients in the Disease Management group
      was statistically significantly improved compared with the start of the study and
      with the control group. Inpatient respiratory-related costs were only incurred in
      the control group ( 320). No significant differences were found in the case of
      the other direct cost parameters (costs for asthma-related drugs 716 and 720 in
      the control group and DMP group respectively). The indirect costs were higher in
      the DMP group due to more frequent disability. With regard to overall symptoms, a
      pronounced reduction was only achieved in the DMP group. The mean FEV (1)
      measured in the physicians practice rose in the DMP group from 1.82 l to 1.89 l,
      whereas in the control group it fell slightly from 1.84 l to 1.78 l. The daily
      FEV (1) measurements at patient's home showed an increase of about 10 % in the
      values after 12 months. CONCLUSIONS: The tested DMP for asthmatics brought about
      a significant improvement in the state of health, asthmatic symptoms and lung
      function of asthmatics. The direct costs of treatment were also found to be
      lower.

PMID- 15724224
TI  - [Second-line treatment of malignant pleural mesothelioma with Pemetrexed (Alimta)
      -- a case report].
AB  - Malignant Pleural Mesothelioma is regarded as a tumour, which lacks chemo
      sensitivity. However, patients are able to benefit from a first line
      chemotherapy, as indicated in a currently published randomised study. Here the
      case of a 75 year old patient will be reported, who has been diagnosed with
      malignant pleural mesothelioma for 4 years. After a first line therapy with
      Gemcitabine/Oxaliplatin, partial remission was assessed. 15 months later a
      distinct progress was detected. After a second line therapy with Pemetrexed a
      sound partial response could be determined radiologically and clinically. This
      case history is supposed to exemplify that patients with malignant pleural
      mesothelioma should not only be considered for a first line therapy, but that a
      second line therapy may also be offered to a certain group of patients. The new
      substance Pemetrexed (Alimta) offers an excellent alternative with a very good
      efficacy profile and a favourable spectrum of side effects.

PMID- 15724225
TI  - [A connection between allergic rhinitis and allergic asthma? The "one-airway-one
      disease"-hypothesis].
AB  - The nose and the lungs are anatomically and physiologically divided which lead to
      separated strategies in diagnostic and therapy. The upper airways, from the nose
      and lungs may account for the traditional division in upper and lower airways.
      Nonetheless a link between upper and lower respiratory tracts has been repeatedly
      observed in the past decades making the current division in two separate entities
      an arbitrary dichotomy. Once allergic rhinitis and asthma are two manifestation
      of the atopic syndrome it is logical to expect that allergy is not a disease
      confined to specific target organ rather to a broad spectrum of clinical
      manifestations. This hypothesis has been supported from various observations:
      Both, allergic asthma and allergic rhinitis are characterized by a similar if not
      an identical inflammatory process in which mast cells and eosinophils appear to
      be the major effector cells, high comorbidity of both allergic manifestations as
      shown in epidemiologic studies. Both diseases are caused by the interaction of
      genetic susceptibility with environmental factors. In this review, the latest
      developments in epidemiology and pathophysiology with regard to nasobronchial
      interaction in allergic airway disease will be discussed.

PMID- 15724226
TI  - [Management of malignant pleural effusions].
AB  - Malignant pleural effusions with dyspnoea as their most common presenting symptom
      are a frequent clinical problem in patients with neoplastic disease. Lung
      carcinoma is the leading cause, followed by breast carcinoma and malignant
      lymphoma. The frequency of malignant mesothelioma is increasing in industrialized
      countries. In this overview, which is based on the ERS/ATS Statement 2001, the
      diagnostic approach, the differential diagnosis including causes of paramalignant
      effusions, as well as the therapeutic possibilities are described. Pleurodesis is
      the most important therapeutic modality, today preferably via thoracoscopic talc
      poudrage. Alternative local and systemic treatment options are discussed in
      detail. A special emphasis is put on the epidemiology, diagnosis, treatment, and
      prognosis of malignant effusions in patients with lung and breast carcinomas, and
      with lymphomas. Finally, open questions are listed which need future research,
      which will hopefully improve the treatment and prognosis of malignant pleural
      effusions.

PMID- 15724227
TI  - [Efficacy and safety of sublingual immunotherapy].

PMID- 15724228
TI  - [Topical highlights from the academy for pneumological continuing education].

PMID- 15724229
TI  - [In memoriam Prof. Dr. Severin Daum].

PMID- 15724230
TI  - [Alexander G. Chuchalin on the occasion of his 65th Birthday].

PMID- 15724231
TI  - [Guidelines for dialysis. Replacement therapy for acute renal failure in
      critically ill patients].
AB  - Acute renal failure (ARF) in patients admitted to the intensive care unit (ICU)
      is mostly caused by ischemic or toxic injury, with a higher incidence in the
      latest years due to the growing number of interventions in cardiac and vascular
      surgery and to the general enhancement of reanimation techniques, which allow a
      better outcome among ICU patients. In critically ill patients, the ARF incidence
      reported in the literature ranges between 1 and 25%. Among ICU patients with ARF
      the mortality is between 40 and 65%, much more than in patients without this
      complication. Higher mortality rates, longer hospitalisation times and higher
      therapy costs demand from us an early diagnosis and treatment of ARF. Due to the
      lack of controlled and randomized proofs, recommended criteria for starting renal
      replacement therapy (RRT) in critical ARF patients might overlap with those for
      ESRD therapy. Moreover, randomised and controlled trials, confirming the actual
      efficacy of early onset of RRT on the mortality rate, are not yet available. As
      for stable ESRD patients, a direct relationship between dialytic doses and
      mortality and morbidity has been established for ARF patients. For ARF patients,
      as well as for ESRD patients, a minimum Kt/V of 1.2 three times a week should be
      ensured, although higher doses for critical ARF patients may achieve better
      results. The choice between intermittent (IRRT) and continuous renal replacement
      therapy (CRRT) in these patients is still a controversial issue. In spite of the
      fact that most studies report a better outcome in patients treated with CRRT, a
      recent meta-analysis failed to demonstrate any difference on the relative risk
      (RR) of mortality and on the rate of renal recovery between patients treated with
      either IRRT or CRRT. Furthermore, the use of peritoneal dialysis for the
      treatment of ARF patients in ICU has not been dismissed yet; so far this is
      indeed considered to be the technique of choice in some specific clinical
      situations. The intrinsic urgency of dialysis in ARF patients entails the use of
      temporary central venous catheters. The internal right jugular vein is usually
      preferred for these catheters because of the easier insertion and the lower risk
      of stenosis and thrombosis. The anticoagulant procedure should be chosen on the
      basis of patient characteristics, treatment typology and the likelihood of
      effectively monitoring its action. The choice of buffers in the dialysate, mostly
      lactate or bicarbonate, should depend on patient characteristics; so far,
      however, controlled but not randomized studies do not show any significant
      difference in the correction of metabolic acidosis between lactate and
      bicarbonate.

PMID- 15724232
TI  - Generating survival times to simulate Cox proportional hazards models.
AB  - Simulation studies present an important statistical tool to investigate the
      performance, properties and adequacy of statistical models in pre-specified
      situations. One of the most important statistical models in medical research is
      the proportional hazards model of Cox. In this paper, techniques to generate
      survival times for simulation studies regarding Cox proportional hazards models
      are presented. A general formula describing the relation between the hazard and
      the corresponding survival time of the Cox model is derived, which is useful in
      simulation studies. It is shown how the exponential, the Weibull and the Gompertz
      distribution can be applied to generate appropriate survival times for simulation
      studies. Additionally, the general relation between hazard and survival time can
      be used to develop own distributions for special situations and to handle
      flexibly parameterized proportional hazards models. The use of distributions
      other than the exponential distribution is indispensable to investigate the
      characteristics of the Cox proportional hazards model, especially in non-standard
      situations, where the partial likelihood depends on the baseline hazard. A
      simulation study investigating the effect of measurement errors in the German
      Uranium Miners Cohort Study is considered to illustrate the proposed simulation
      techniques and to emphasize the importance of a careful modelling of the baseline
      hazard in Cox models.

PMID- 15724233
TI  - Design and performance of a sheathless capillary electrophoresis/mass
      spectrometry interface by combining fused-silica capillaries with gold-coated
      nanoelectrospray tips.
AB  - A simple sheathless capillary electrophoresis (CE)/mass spectrometry (MS)
      interface was constructed by combining widely used nanospray needles with fused
      silica capillaries and it was successfully applied for the separation of
      peptides. The end of the CE capillary was pulled to a taper, etched and then
      fitted into the metal-coated nanospray borosilicate capillary. The nanospray
      needle can be used for several CE runs, but it can be easily and rapidly changed
      in the case of accidental breakage or evaporation of the coating. A fast
      capillary electrochromatographic method was also developed for MS analysis of
      peptides containing numerous basic amino acids.

PMID- 15724234
TI  - Thin-layer chromatography/electrospray ionization triple-quadrupole linear ion
      trap mass spectrometry system: analysis of rhodamine dyes separated on reversed
      phase C8 plates.
AB  - The direct analysis of separated rhodamine dyes on reversed-phase C(8) thin-layer
      chromatography plates using a surface sampling/electrospray emitter probe coupled
      with a triple-quadrupole linear ion trap mass spectrometer is presented. This
      report represents continuing work to advance the performance metrics and utility
      of this basic surface sampling electrospray mass spectrometry system for the
      analysis of thin-layer chromatography plates. Experimental results examining the
      role of sampling probe spray end configuration on liquid aspiration rate and gas
      phase ion signal generated are discussed. The detection figures-of-merit afforded
      by full-scan, automated product ion and selected reaction monitoring modes of
      operation were examined. The effect of different eluting solvents on mass
      spectrum signal levels with the reversed-phase C(8) plate was investigated. The
      combined effect of eluting solvent flow-rate and development lane surface scan
      rate on preservation of chromatographic resolution was also studied. Analysis of
      chromatographically separated red pen ink extracts from eight different pens
      using selected reaction monitoring demonstrated the potential of this surface
      sampling electrospray mass spectrometry system for targeted compound analysis
      with real samples.

PMID- 15724235
TI  - Potential of laser ablation and laser desorption mass spectrometry to
      characterize organic and inorganic environmental pollutants on dust particles.
AB  - Stainless steel factories are known to release particles into the atmosphere.
      Such particulate matter contains significant amounts of heavy metals or toxic
      inorganic compounds and organic pollutants such as, for example, Cr(VI) and
      polycyclic aromatic hydrocarbons (PAHs). The investigation of Cr(VI) and PAHs is
      often complicated by the associated matrix. Organic and inorganic pollutants
      present in stainless steel dust particles have been investigated with the same
      laser microprobe mass spectrometer according to two original methodologies. These
      analytical methods do not require time-consuming pretreatment (extraction,
      solubilization) or preconcentration steps. More specifically, experiments are
      conducted with a Fourier transform ion cyclotron resonance mass spectrometer
      coupled to an ArF (193 nm) or a tripled frequency Nd-YAG (355 nm) laser.
      Experiments at 355 nm allow the nature of the most frequently occurring
      Cr(III)/Cr(VI) compounds in dust particles to be identified. Examination of PAHs
      at 193 nm is assisted by the formation of pi-complexes with 7,7',8,8'
      tetracyanoquinodimethane to prevent their evaporation in the mass spectrometer
      during analysis and to ensure an increase in sensitivity.

PMID- 15724236
TI  - No acute effect of nateglinide on postprandial lipid and lipoprotein responses in
      subjects at risk for type 2 diabetes.
AB  - BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on
      the postprandial triglyceride and lipoprotein responses in subjects at risk for
      type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree
      relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/-
      2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6
      mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal
      tolerance tests with either nateglinide or placebo given 10 min prior to the
      meals in randomized order. Lipoprotein fractions were separated by density
      gradient ultracentrifugation. First-phase insulin secretion was assessed by an
      intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin
      sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)).
      RESULTS: The 1-h insulin levels during the meal tolerance test were significantly
      higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well
      as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/-
      4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h
      postprandial glucose response by around 60% compared to placebo (p < 0.001). In
      contrast, no significant lowering was seen in the excursion of postprandial
      triglycerides in total plasma or lipoprotein fractions. Consistently, the
      concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was
      not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide
      reduces, as expected, the postprandial glucose concentration, but no reduction in
      triglyceride or lipoprotein responses are seen in subjects at risk for type 2
      diabetes.

PMID- 15724237
TI  - A new method to analyze matrix-assisted laser desorption/ionization time-of
      flight peptide profiling mass spectra.
AB  - In protein and peptide mass spectrometry in which profiling of peaks is involved,
      their masses and intensities are important characteristics. Because of the
      relative low reproducibility of peak intensities associated with complex samples
      in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS), it is difficult to accurately assess the number of peaks and their
      intensities. In this study we evaluate these two characteristics for tryptic
      digests of cerebro-spinal fluid. We observed that the reproducibility of peak
      intensities was relatively poor (CV = 42%) and that additional normalization or
      spiking did not lead to a large improvement (CV = 30%). Moreover, at least seven
      mass spectra per sample were required to obtain a reliable peak list. An
      improvement of the sensitivity (i.e., eventually more peaks are detected) is
      observed if more replicates per sample are measured. We conclude that the
      reproducibility and sensitivity of peptide profiling can be significantly
      improved by a combination of measuring at least seven spectra per sample with a
      dichotomous scoring of the intensities. This approach will aid the analysis of
      large numbers of mass spectra of patient samples in a reproducible way for the
      detection and validation of candidate biomarkers.

PMID- 15724238
TI  - Endogenous association of Bim BH3-only protein with Mcl-1, Bcl-xL and Bcl-2 on
      mitochondria in human B cells.
AB  - Bim is an essential regulator of lymphoid system homeostasis and appears
      essential for B cell apoptosis induction. The mechanism by which Bim isoforms are
      held in an inactive form remains poorly documented in normal B cells. In the
      current study, we demonstrated that in normal tonsil B cells the three major Bim
      isoforms are strongly associated with the anti-apoptotic Bcl-2 family members Mcl
      1, Bcl-2 and Bcl-x(L). On the other hand, only a weak association of BimEL and L
      with the dynein LC8 chain has been found. In addition, there is no free Bim in
      normal B cells. Moreover, subcellular fractionation demonstrated that Bim and the
      anti-apoptotic counterparts are localized preferentially in the mitochondria-rich
      fraction. The fact that most Bim was found in this fraction supports the
      hypothesis that it is sequestered by anti-apoptotic molecules in mitochondria
      where its pro-apoptotic activity is controlled. Of interest, BimS is essentially
      complexed to Mcl-1 and the Mcl-1/Bim complex is the most abundant among the three
      types of complexes. This supports the idea that this complex is critical for the
      control of B cell death. In conclusion, these results favor a model in which Bim
      release from anti-apoptotic proteins is a critical event for initiation of
      apoptosis.

PMID- 15724239
TI  - Characterizing the electrospray ionization mass spectral fragmentation pattern of
      indole derivatives synthesized from 2-keto glycosides.
AB  - Four indole derivatives synthesized from 2-keto glycosides were analyzed by
      electrospray ionization tandem mass spectrometry (ESI-MSn) with low-energy
      collision-induced dissociation to establish a general structural elucidation of
      indole derivatives. Their fragmentation pathways are proposed on the basis of the
      MSn studies and deuterium-labeled experiments. Indole derivatives undergo
      complicated gas-phase rearrangements in addition to simple bond cleavages. A
      rearrangement, which involves a contraction of the six-membered ring, was
      observed and a mechanism was proposed. The observations may have some potential
      applications in the interpretation of the mass spectra of indole derivatives.

PMID- 15724240
TI  - Association between serum leptin concentration and white blood cell count in
      middle-aged Japanese men and women.
AB  - BACKGROUND: Leptin's hematopoietic or proinflammatory role has been
      experimentally reported. We investigated whether serum leptin concentrations are
      associated with white blood cell (WBC) counts in humans. METHODS: Serum leptin
      concentrations of Japanese civil servants aged 40 to 59 years (1082 men and 200
      women) were analyzed in relation to their WBC count. Serum leptin concentrations
      and WBC counts were measured by radioimmunoassay and automated particle counter
      respectively, using samples obtained at the time of the participants' annual
      health checkups. RESULTS: The geometric mean (+/-geometric standard deviation)
      leptin concentrations were 3.25 +/- 1.82 ng/mL and 6.25 +/- 3.99 ng/mL, and the
      geometric mean WBC counts, 5770 +/- 1269/mm(3) and 5107 +/- 1228/mm(3), in men
      and women respectively. The WBC count adjusted for age, body mass index (BMI),
      physical activity, and drinking and smoking habits increased together with the
      increase in leptin concentration. Multiple linear regression against WBC count by
      the leptin concentration and those covariates revealed a significant and
      independent association with serum leptin concentration especially in women
      (standardized beta = 0.31, p < 0.001), and also in men (standardized beta = 0.17,
      p < 0.001). BMI was not significantly associated with WBC counts in the
      multivariate model adjusting for leptin levels in both sexes. CONCLUSIONS: Our
      results are in line with leptin's hematopoietic or proinflammatory functions. The
      increased WBC counts often observed in obese people would be mediated by the
      increased leptin concentration.

PMID- 15724241
TI  - Long-term loss of canonical NKT cells following an acute virus infection.
AB  - NKT cell activation plays an important role in regulating innate and adaptive
      immunity during infection. We have previously found that there is a dramatic
      reduction in the NKT cell population on day 3 after an acute lymphocytic
      choriomeningitis virus (LCMV) infection. In this study, we report that this loss
      continued for at least 3 months and was not simply due to internalization of the
      TCR. Concomitant with the decrease in NKT cells was an increase in the percentage
      of Annexin V(+) NKT cells that remained in vivo, suggesting that the reduction in
      NKT cells at these late stages post-infection occurred by activation-induced cell
      death. Interestingly, APC from LCMV-infected mice could activate NKT cells in
      vitro at higher levels than those from uninfected mice and was concomitant with
      an increase in apoptosis in NKT cells. However, this could not be blocked by mAb
      to murine CD1d, and APC from LCMV-infected (but not uninfected) CD1d1-deficient
      mice could also stimulate NKT cells. Collectively, our data suggest that the
      activation and subsequent long-term loss of NKT cells is a normal component of
      the host's antiviral immune response, and this occurs in a CD1d-independent
      manner.

PMID- 15724242
TI  - The Mycobacterium tuberculosis cell wall component mycolic acid elicits pathogen
      associated host innate immune responses.
AB  - Recognition of conserved pathogen-associated molecular patterns constitutes a
      crucial step in the initiation of innate immune responses. We studied the
      contribution to the host-pathogen interaction of mycolic acid (MA), a major lipid
      component of the cell envelope of the macrophage intracellular pathogen
      Mycobacterium tuberculosis and other mycobacteria. MA administered to the
      peritoneal cavity or to the airways induced a unique macrophage morphotype,
      similar to the foamy macrophage derivatives observed in tuberculous granulomas
      and characterized by intracellular accumulation of neutral lipids and entry into
      mitosis. When assayed for production of inflammatory mediators, a conditioning
      rather than a direct activation of the MA-elicited foamy macrophages was
      observed. MA enabled production of IFN-gamma and myeloperoxidase, enhanced TNF
      alpha production and suppressed IL-10 upon renewed exposure to innate triggers.
      Intratracheal instillation of MA mimicked additional features of the airway
      response to M. tuberculosis infection, namely a rapid but transient neutrophil
      influx and IL-6 production and a chronic IL-12 production. These MA-elicited
      cellular innate defenses and the accompanying formation of foamy macrophages
      identify for the first time the foamy macrophage morphotype as part of the host
      response to a pathogen-associated structure. Furthermore, these results
      characterize MA as a direct trigger of innate immunity, distinct from Toll-like
      receptor ligands.

PMID- 15724243
TI  - Novel method for detection of virus-specific CD41+ T cells indicates a decreased
      EBV-specific CD4+ T cell response in untreated HIV-infected subjects.
AB  - A lower function of EBV-specific CD8(+) T cells in HIV-infected subjects could be
      related to a lack of specific CD4(+) T cell help. Therefore, we studied EBV
      specific CD4(+) T cells in both healthy donors and untreated or highly active
      antiretroviral therapy (HAART)-treated HIV-seropositive homosexual men. To this
      end, PBMC were stimulated with overlapping peptide pools from a latent and a
      lytic EBV protein, EBV nuclear antigen (EBNA)1 and EBV lytic-switch protein ZEBRA
      (BZLF1), respectively. EBV-specific CD4(+) T cell frequencies measured directly
      ex vivo were low. To measure EBV-specific memory CD4(+) T cells, capable of both
      expansion and IFN-gamma production upon antigenic challenge, we developed a
      specific and reproducible assay, combining ex vivo expansion of specific T cells
      with flow cytometric analysis of IFN-gamma production. Untreated HIV-infected
      individuals had a lower CD4(+) T cell response to both EBNA1 and BZLF1 as
      compared to healthy EBV carriers and HAART-treated HIV-positive subjects. This
      suggests loss of EBV-specific CD4(+) T cells due to HIV infection, while HAART
      might restore this response. In addition, we found an increase in the EBNA1
      specific CD8(+) T cell response in HAART-treated subjects. Interestingly, numbers
      of EBV-specific CD4(+) and CD8(+) T cells were inversely correlated with EBV
      viral load, suggesting an important role also for EBV-specific CD4(+) T cells in
      the control of EBV infection.

PMID- 15724244
TI  - Efficient homologous prime-boost strategies for T cell vaccination based on virus
      like particles.
AB  - Induction of high frequencies of specific T cells by vaccination requires prime
      boost regimens. To reach optimal immune responses, it is necessary to use
      different vectors for priming and boosting as e.g. DNA vaccination followed by
      boosting with a recombinant viral vector. Here, we show that vaccines based on
      virus-like particles (VLP) displaying peptide epitopes are equally effective to
      induce CTL responses if used in a homologous or heterologous prime-boost setting.
      Strikingly, high frequencies (>20% of CD8(+) cells) of protective CTL could be
      induced and maintained by weekly injection of VLP. Thus, the use of VLP may avoid
      the requirement for complicated heterologous prime-boost regimens, facilitating
      the development of effective T cell-based vaccines.

PMID- 15724245
TI  - MyD88 is critical for the development of innate and adaptive immunity during
      acute lymphocytic choriomeningitis virus infection.
AB  - We investigated the roles of Toll-like receptor 2 (TLR2) and myeloid
      differentiation factor 88 (MyD88) in the course of a lymphocytic choriomeningitis
      virus (LCMV) infection and revealed the following: (i) studies of transfected
      cells and murine peritoneal macrophages demonstrated that TLR2 and MyD88 are
      essential for the initial pro-inflammatory cytokine response (human IL-8, mouse
      IL-6) to LCMV; (ii) TLR2 knockout (KO) mice and MyD88 KO mice challenged with
      LCMV produced less IL-6 and monocyte chemotactic protein-1 in the serum than wild
      type mice; (iii) in contrast to inflammatory cytokines, the production of type 1
      IFN (IFN-alpha) in response to LCMV was MyD88 independent; (iv) MyD88 plays an
      essential role in antiviral CD8(+) T cell responses, CD8(+) T cells in MyD88 KO
      mice were defective in their expression of intracellular antiviral cytokines; and
      (v) the failure of MyD88 KO mice to activate CD8(+) T cells was accompanied by
      persistent viral infection in MyD88 KO mice. We demonstrate that TLR-mediated
      responses are important in the innate immune response to LCMV and that MyD88 is
      essential for the control of the LCMV infection and the maturation/activation of
      virus-specific CD8(+) T cells.

PMID- 15724248
TI  - TGF-beta-treated microglia induce oligodendrocyte precursor cell chemotaxis
      through the HGF-c-Met pathway.
AB  - In acute experimental autoimmune encephalomyelitis (EAE), demyelination is
      induced by myelin-specific CD4(+) T lymphocytes and myelin-specific antibodies.
      Recovery from the disease is initiated by cytokines which suppress T cell
      expansion and the production of myelin-toxic molecules by macrophages. Th2/3 cell
      derived signals may also be involved in central nervous system (CNS) repair.
      Remyelination is thought to be initiated by the recruitment and differentiation
      of oligodendrocyte precursor cells (OPC) in demyelinated CNS lesions. Here, we
      report that unlike Th1 cytokines (TNF-alpha, IFN-gamma), the Th2/3 cytokine TGF
      beta induces primary microglia from C57BL/6 mice to secrete a chemotactic factor
      for primary OPC. We identified this factor to be the hepatocyte growth factor
      (HGF). Our studies show that TGF-beta-1-2-3 as well as IFN-beta induce HGF
      secretion by microglia and that antibodies to the HGF receptor c-Met abrogate OPC
      chemotaxis induced by TGF-beta2-treated microglia. In addition we show spinal
      cord lesions in EAE induced in SJL/J mice to contain both OPC and HGF producing
      macrophages in the recovery phase, but not in the acute stage of disease. Taken
      these findings, TGF-beta may play a pivotal role in remyelination by inducing
      microglia to release HGF which is both a chemotactic and differentiation factor
      for OPC.

PMID- 15724247
TI  - Serum amyloid A activates NF-kappaB and proinflammatory gene expression in human
      and murine intestinal epithelial cells.
AB  - Serum amyloid A (SAA) is an acute-phase protein whose levels positively correlate
      with disease activity in inflammatory bowel diseases. In this study we
      investigated the impact of SAA on NF-kappaB signaling and proinflammatory gene
      expression in intestinal epithelial cells (IEC). Human HT-29 and Caco-2
      monolayers were stimulated with recombinant SAA and NF-kappaB activation/NF
      kappaB-dependent gene expression measured. Adenoviral dominant negative mutants
      IkappaB-alpha (Ad5IkappaBAA) were utilized to determine the contribution of NF
      kappaB signaling pathway to SAA-dependent gene expression. Intestinal explant and
      primary IEC derived from kappaB-EGFP transgenic mice were exposed to SAA and NF
      kappaB-dependent enhanced green fluorescent protein (EGFP) fluorescence measured.
      SAA induced IkappaB-alpha degradation, RelA serine 536 (S536) phosphorylation, NF
      kappaB transcriptional activity, RelA recruitment to the IL-8 gene promoter and
      endogenous gene expression (IL-8, COX-2) in HT-29 cells. Further, Ad5IkappaBAA
      abrogated SAA-induced RelA nuclear translocation, NF-kappaB transcriptional
      activity and IL-8 gene expression. SAA-dependent IL-8 gene expression required
      activation of the MAPK ERK, p38 and JNK in HT-29 cells. Finally, SAA induced EGFP
      expression in intestinal explants isolated from kappaB-EGFP transgenic mice and
      enhanced RelA and IkappaBalpha phosphorylation in primary IEC. This indicates
      that SAA potentially participate in the inflammatory process by virtue of its
      ability to activate proinflammatory signaling in IEC.

PMID- 15724253
TI  - Atmosphere, a chemical reactor-formation pathways of secondary organic aerosols.

PMID- 15724254
TI  - Hetero-aggregate compounds of aryl and alkyl lithium reagents: a structurally
      intriguing aspect of organolithium chemistry.
AB  - Organolithium compounds are often depicted as mononuclear species. However, such
      compounds are in fact aggregated species and can form hetero-aggregates
      containing different organic groups, including heteroatom groups. In reactions
      involving organolithium reagents, the "pure" homo-aggregate organolithium
      compound can change into a hetero-aggregate, which has a different structure and
      reactivity to the homo-aggregate. This fact is often overlooked. When there are
      chiral centers in the organolithium reagent or the substrate, diastereoselective
      self-assembly (the preferential formation of a particular diastereoisomeric
      aggregate) plays a role. The importance of these contributions in understanding
      the structure and reactivity patterns of organolithium reagents is the focus of
      this Minireview.

PMID- 15724249
TI  - Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion
      during persistent antigen stimulation.
AB  - Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus,
      hepatitis C virus and LCMV. In the case of LCMV, persistence may often be
      associated with exhaustion of CD8(+) T cells. We demonstrate here that persistent
      antigen suppressed IL-7Ralpha expression and this correlated with T cell
      exhaustion and reduced expression of the anti-apoptotic molecule B cell
      leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only
      temporarily suppressed IL-7Ralpha expression, failed to induce T cell exhaustion,
      and primed T cells. Persistent antigen also suppressed IL-7Ralpha expression on
      primed T cells and this correlated with exhaustion of a previously stable primed
      T cell population. These findings suggest that antigen longevity regulates T cell
      fate.

PMID- 15724255
TI  - Concomitant monoreduction and hydrogenation of unsaturated cyclic imides to
      lactams catalyzed by ruthenium compounds.

PMID- 15724257
TI  - Fluorophenoxycarbene inside a hemicarcerand: a bottled singlet carbene.

PMID- 15724256
TI  - Metal clusters as ligands: substitution of Fe ions in Fe/Mo/S clusters by
      thiophilic Cu(I) ions to give clusters with [Cu4Mo2Fe2S8]4+ and [Cu5Mo3Fe4S11]6+
      cores.

PMID- 15724258
TI  - An electroactive nitrogen-rich [4.4]ferrocenophane displaying redox-switchable
      behavior: selective sensing, complexation, and decomplexation of Mg2+ ions.

PMID- 15724259
TI  - A small-molecule agonist of the Wnt signaling pathway.

PMID- 15724261
TI  - Single-wall carbon nanotubes as integrative building blocks for solar-energy
      conversion.

PMID- 15724260
TI  - Controlled assembly of macromolecular beta-sheet fibrils.

PMID- 15724262
TI  - Vicinal tungsten-tungsten coupling constants in polyoxotungstates: DFT
      calculations challenge an empirical rule.

PMID- 15724263
TI  - The synthesis of hybrids of D-galactose with 1-deoxynojirimycin analogues as
      glycosidase inhibitors.

PMID- 15724264
TI  - Finite enantiomeric excess nucleated in an achiral banana mesogen by chiral
      alignment surfaces.

PMID- 15724265
TI  - A two-in-one crystal: uptake of two different guests into two distinct channels
      of a biporous coordination network.

PMID- 15724266
TI  - Adult myeloid leukaemia and radon exposure: a Bayesian model for a case-control
      study with error in covariates.
AB  - The possible association between radon exposure in dwellings and adult myeloid
      leukaemia had been explored in an Italian province by a case-control study. A
      total of 44 cases and 211 controls were selected from death certificates file. No
      association had been found in the original study (OR = 0.58 for > 185 vs 80 < or
      = Bq/cm). Here we reanalyse the data taking into account the measurement error of
      radon concentration and the presence of missing data. A Bayesian hierarchical
      model with error in covariates is proposed which allows appropriate imputation of
      missing values. The general conclusion of no evidence of association with radon
      does not change, but a negative association is not observed anymore (OR = 0.99
      for > 185 vs 80 < or = Bq/cm). After adjusting for residential house radon and
      gamma radiation, and for the multilevel data structure, geological features of
      the soil is associated with adult myeloid leukaemia risk (OR = 2.14, 95 per cent
      Cr.I. 1.0-5.5).

PMID- 15724267
TI  - The withdrawal of rofecoxib.

PMID- 15724268
TI  - Low-temperature 1H and 13C NMR spectra of N-substituted 1,2,3,4
      tetrahydropyrazino[1,2-a]indoles.
AB  - The temperature-dependent (1)H and (13)C NMR spectra of 2-(2-butynyl)-10-methyl
      1,2,3,4-tetrahydropyrazino[1,2-a]indole (4) (as a representative example of 1-9)
      in CFCl(3) + CD(2)Cl(2) solution are described and discussed. Below 183 K, the
      hexahydropyrazine ring inversions become slow on the NMR time-scale and 4 exists
      in principle as two conformational diastereomers. In fact, only one was observed
      with the N-2 substituent in an equatorial position as shown by a low-temperature
      NOESY experiment. The energy barrier for conformational interchange was
      calculated from NMR data to be 8.3 kcal mol(-1) (1 kcal = 4.184 kJ), in agreement
      with quantum chemical calculations. Unambiguous assignments for all proton and
      carbon resonances of 1-9 were made using 1D (APT, DEPT, NOE difference) and 2D
      (COSY, NOESY, gHMQC, gHMBC) NMR techniques.

PMID- 15724269
TI  - Space-time models with time-dependent covariates for the analysis of the temporal
      lag between socioeconomic factors and lung cancer mortality.
AB  - The relationship between socioeconomic factors and mortality for lung cancer is
      investigated. To identify the proper lag time between socioeconomic factors and
      lung cancer mortality, a space-time hierarchical Bayesian model with time
      dependent covariates is adopted. A real example on lung cancer mortality, males,
      in Tuscany (Italy) during the period 1971-1999, is provided. Results confirm the
      presence of an association between mortality for lung cancer and socioeconomic
      factors with a temporal lag (latency time) of at least 10 years.

PMID- 15724270
TI  - Structure investigation of maltacine B1a, B1b, B2a and B2b: cyclic peptide
      lactones of the maltacine complex from Bacillus subtilis.
AB  - A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which
      we named maltacines, has recently been described. The structure elucidation of
      four of them is reported in this paper. The amino acid sequences and structures
      of the peptides were found by MSn of the ring-opened linear peptides that gave
      uninterrupted sequences of Bn and Y''n ions. The identities of three unknown
      residues in the sequences were solved by a combination of derivatization with
      phenyl isothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange.
      The nature and position of the cyclic structure were revealed by a chemoselective
      ring opening with Na18OH and was found to be a lactone formed between a hydroxyl
      of residue number 4 and the C-terminal amino acid number 12. For verification of
      the structure of the B2+ ion, peptides with different combinations of P/Q and P/K
      at the N-terminus were synthesized. The structures of the four peptides were
      found to be as follows: B1a/B2a, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-Orn-103-Y-I-OH);
      and B1b/B2b, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-K-103-Y-I-OH).

PMID- 15724271
TI  - Electrolytic electrospray ionization mass spectrometry of quaterthiophene-bridged
      bisporphyrins: beyond the identification tool.
AB  - Several quaterthiophene-bridged bisporphyrins were analyzed by electrospray
      ionization mass spectrometry (ESI-MS). The active centers of these molecular
      assemblies are two porphyrins moieties complexed (Z) or not (H) with a metal ion,
      typically Zn(2+), and the spacer is a quaterthiophene. The two end-groups were
      chemically linked to the quaterthiophene spacers by (i) a C--C single bond, (ii)
      a trans double bond or (iii) a triple bond. The formation of charged species
      either by protonation ([M + H](+) and [M + 2H](2+)) or electron(s) loss (M(+) and
      M(2+)), account for the occurrence of electrochemical processes in the basic
      operation of an electrospray source acting in a non-aqueous solvent. The nature
      of the observed charged species is correlated with the electro-oxidation
      properties and proton production by electro-oxidation of residual water. The
      occurence of these electrochemical reaction is proposed when the electroactivity
      of the electrosprayed substrates is not sufficient to support the current demand
      of the ESI source. In this way, the results obtained from the analysed series
      suggest the occurrence of such a process when the interfacial potential of the
      metal capillary reaches a value of 0.75 V vs Ag/AgCl. The results of theoretical
      calculations confirm the importance of the ionization energy with regard to the
      protonation energy in the course of the ionization reaction. The structural
      differences at the porphyrin-linker junctions lead to significantly smaller
      ionization energy in the case of the trans double bond. The MS observation of
      discharged dimers from molecular assemblies, including two complexed porphyrins
      ZZ or two free bases HH as end-group and a triple bond as the quaterthiophene
      bisporphyrin junction, indicates together with molecular modelling (carried out
      at the semi-empirical PM3 level), that the planar and symmetric structures favour
      stacking.

PMID- 15724272
TI  - Gas-phase ion chemistry in XH4--C3H4--ZH3 (X==Si, Ge; Z==N, P) mixtures.
AB  - The gas-phase ion chemistry of silane-allene-ammonia, germane-allene (or propyne)
      ammonia (or phosphine) systems was studied by ion trap mass spectrometry.
      Reaction sequences were determined and rate constants were measured for the main
      processes observed. The mixture containing silane displays higher reactivity with
      respect to that with germane. Comparison with analogous systems provides useful
      information about the reactivity of different hydrocarbon molecules and the
      different affinities of silicon and germanium towards nitrogen and phosphorus.
      The most interesting product ions observed are those containing Si (or Ge), C and
      N (or P) elements together, as these ion species may be considered precursors of
      doped amorphous carbides, which are widely used in semiconductor devices.

PMID- 15724274
TI  - Survey reveals US university licensing up, startup formation down.

PMID- 15724273
TI  - Copper-mediated intra-ligand oxygen transfer in gas-phase complexes with 3
      nitrotyrosine.
AB  - Gas-phase ternary complexes with Cu(II) and 2,2'-bipyridine (bpy) of tyrosine, 3
      aminotyrosine, 3-nitrotyrosine and 3-nitrotyrosine methyl ether are formed
      readily upon electrospraying aqueous methanol solutions containing the
      components. In contrast to Cu(bpy) complexes of tyrosine, 3-aminotyrosine and
      other aromatic amino acids, the complexes of 3-nitrotyrosine and its methyl ether
      undergo unusual collisionally activated dissociations (CADs) that involve Cu
      mediated transfer of an oxygen atom from the nitro group. With 3-nitrotyrosine
      this results in an expulsion of carbonic acid, H(2)CO(3), whereas with 3
      nitrotyrosine methyl ether an OH migration forms Cu(OH)bpy(+) as the predominant
      product. To the best of our knowledge, this is the first case of an intra-ligand
      redox reaction in a gas-phase organometallic complex. The reaction mechanism of
      this unusual dissociation was elucidated by a combination of isotope labeling,
      accurate mass measurements, energy-resolved CAD mass spectra and density
      functional theory calculations of ion structures and relative energies.

PMID- 15724275
TI  - The importance of angels in starting a US biotech venture.

PMID- 15724276
TI  - Susan Sontag.

PMID- 15724277
TI  - Protein.

PMID- 15724278
TI  - CombAlign: a protein sequence comparison algorithm considering recombinations.
AB  - The basic linear treatment of sequence comparisons limits the ability of
      contemporary sequence alignment algorithms to detect non-order-conserving
      recombinations. Here, we introduce the algorithm combAlign which addresses the
      assessment of pairwise sequence similarity on non-order-conserving recombinations
      on a large scale. Emphasizing a two-level approach, combAlign first detects
      locally well conserved subsequences in a target and a source sequence.
      Subsequently, the relative placement of alignments is mapped to a graph.
      Concatenating local alignments to reassemble the target sequence to the fullest
      extent, the maximum scoring path through the graph denotes the best attainable
      combAlignment. Parameters influencing this process can be set to meet the user's
      specific demands. combAlign is applied to examples demonstrating the possibility
      to reflect evolutionary kinship of proteins even if their domains and motifs are
      strongly rearranged.

PMID- 15724279
TI  - Using amino acid patterns to accurately predict translation initiation sites.
AB  - The translation initiation site (TIS) prediction problem is about how to
      correctly identify TIS in mRNA, cDNA, or other types of genomic sequences. High
      prediction accuracy can be helpful in a better understanding of protein coding
      from nucleotide sequences. This is an important step in genomic analysis to
      determine protein coding from nucleotide sequences. In this paper, we present an
      in silico method to predict translation initiation sites in vertebrate cDNA or
      mRNA sequences. This method consists of three sequential steps as follows. In the
      first step, candidate features are generated using k-gram amino acid patterns. In
      the second step, a small number of top-ranked features are selected by an entropy
      based algorithm. In the third step, a classification model is built to recognize
      true TISs by applying support vector machines or ensembles of decision trees to
      the selected features. We have tested our method on several independent data
      sets, including two public ones and our own extracted sequences. The experimental
      results achieved are better than those reported previously using the same data
      sets. Our high accuracy not only demonstrates the feasibility of our method, but
      also indicates that there might be "amino acid" patterns around TIS in cDNA and
      mRNA sequences.

PMID- 15724280
TI  - Constructing biological pathway models with hybrid functional Petri nets.
AB  - In many research projects on modeling and analyzing biological pathways, the
      Petri net has been recognized as a promising method for representing biological
      pathways. From the pioneering works by Reddy et al., 1993, and Hofestadt, 1994,
      that model metabolic pathways by traditional Petri net, several enhanced Petri
      nets such as colored Petri net, stochastic Petri net, and hybrid Petri net have
      been used for modeling biological phenomena. Recently, Matsuno et al., 2003b,
      introduced the hybrid functional Petri net (HFPN) in order to give a more
      intuitive and natural modeling method for biological pathways than these existing
      Petri nets. Although the paper demonstrates the effectiveness of HFPN with two
      examples of gene regulation mechanism for circadian rhythms and apoptosis
      signaling pathway, there has been no detailed explanation about the method of
      HFPN construction for these examples. The purpose of this paper is to describe
      method to construct biological pathways with the HFPN step-by-step. The method is
      demonstrated by the well-known glycolytic pathway controlled by the lac operon
      gene regulatory mechanism.

PMID- 15724281
TI  - Modeling and simulation of biological systems with stochasticity.
AB  - Mathematical modeling is a powerful approach for understanding the complexity of
      biological systems. Recently, several successful attempts have been made for
      simulating complex biological processes like metabolic pathways, gene regulatory
      networks and cell signaling pathways. The pathway models have not only generated
      experimentally verifiable hypothesis but have also provided valuable insights
      into the behavior of complex biological systems. Many recent studies have
      confirmed the phenotypic variability of organisms to an inherent stochasticity
      that operates at a basal level of gene expression. Due to this reason,
      development of novel mathematical representations and simulations algorithms are
      critical for successful modeling efforts in biological systems. The key is to
      find a biologically relevant representation for each representation. Although
      mathematically rigorous and physically consistent, stochastic algorithms are
      computationally expensive, they have been successfully used to model
      probabilistic events in the cell. This paper offers an overview of various
      mathematical and computational approaches for modeling stochastic phenomena in
      cellular systems.

PMID- 15724282
TI  - Molecular chaperones: proposal of a systematic computer-oriented nomenclature and
      construction of a centralized database.
AB  - Molecular chaperones are a wide group of unrelated protein families whose role is
      to assist others proteins. Comparably, under environmental stress, stress
      proteins behave as biocatalysts of protein stabilization. Stress proteins include
      a large class of proteins that were originally termed heat shock proteins (HSPs)
      due to their initial discovery in tissues exposed to elevated temperatures. Many,
      but not all, stress proteins and HSPs are molecular chaperones. Moreover, not all
      HSPs are derivable from stress. HSPs are structurally diversified by the
      contribution of various domains having specific roles. HSPs have been grouped,
      mainly on the basis of their molecular masses, into specific families that
      include small HSPs (sHSPs)/alpha-crystallins, HSP10s, HSP40s, HSP60s, HSP70s,
      HSP90s, HSP100s and HSP110s. The names of these major families are historical
      artefacts with limited information content. Using the current databases, names
      and proteic domains of many molecular chaperones in different species were
      analyzed. Although traditional names of HSPs are trivial, it is unrealistic to
      suggest replacing them, because they are preferred and widely used. Here we
      suggest that these traditional names be chaperoned, in silico, by a systematic
      nomenclature. Thus, for example, with the same intent of use of [trioxygen: O3]
      for ozone, we propose here C7HSP70[Ehsa]ER-P11021 for GRP78 (78 kDa endoplasmic
      Human molecular chaperone in HSP70 superfamily with P11021 as its accession
      number in the database of the National Center for Biotechnology Information
      (NCBI)). The proposed systematic computer-oriented naming and classification
      method is designed for HSPs and also their partners based on the number of amino
      acids, domain structure, phylogenetic domain, localization in the cell and
      accession number as stated in the NCBI. Arabidopsis thaliana was analyzed as a
      model, because it contains a large number of various HSPs localized in several
      organelles. Overall, this naming system helps in building, optimizing and
      managing a novel online database entirely devoted to HSPs. The purported
      taxonomy, coupled with the newly constructed database, can contribute to studies
      involving large amounts of stored data on HSPs.

PMID- 15724283
TI  - GeneInfoViz: constructing and visualizing gene relation networks.
AB  - Large amounts of knowledge about genes have been stored in public databases. One
      of the most challenging problems in Bioinformatics is, given all the information
      about the genes in the databases, determining the relationships between the
      genes. For example, how can we determine if genes are related and how closely
      they are related based on existing knowledge about their biological roles. We
      developed GeneInfoViz, a web tool for batch retrieval of gene information and
      construction and visualization of gene relation networks. We created a database
      containing compiled Gene Ontology information for the genes of several model
      organisms. Users can batch search for a group of genes and get the Gene Ontology
      terms that are associated with the genes. Directed acyclic graphs are generated
      to show the hierarchical structure of the Gene Ontology tree. GeneInfoViz
      calculates an adjacency matrix to determine whether the genes are related and, if
      so, how closely they are related based on biological processes, molecular
      functions, or cellular components they are associated with and then displays a
      dynamic graph layout of the network among the selected genes.

PMID- 15724284
TI  - Using prior knowledge to improve genetic network reconstruction from microarray
      data.
AB  - The use of Bayesian Network methods to recover transcriptional regulatory
      networks from static microarray data is an active area of bioinformatics
      research. However, early work in this area lacked realistic analysis of the
      effects of data set size on learning performance and ignored the potentially
      immense benefits of using prior biological knowledge. More recent work which has
      utilized such information has tended to focus on qualitative descriptions of the
      results. In this paper, we construct a detailed, realistic model for glucose
      homeostasis and use this model to generate static, synthetic gene expression
      data. We then use a Bayesian Network method to reconstruct this genetic network
      from the synthetic microarray data utilizing various amounts and types of prior
      knowledge. By quantitatively analyzing the effects of data set size and the
      incorporation of different types of prior biological knowledge on our ability to
      reconstruct the original network, we show that characteristic portions of genetic
      networks can be reconstructed from microarray data. Incorporating prior knowledge
      into the learning scheme greatly reduces the data required, allowing these
      reverse engineering techniques to be used to learn regulatory interactions from
      microarray data sets of realistic size.

PMID- 15724285
TI  - A novel genomics approach for the identification of drug targets in pathogens,
      with special reference to Pseudomonas aeruginosa.
AB  - Complete genome sequences of several pathogenic bacteria have been determined,
      and many more such projects are currently under way. While these data potentially
      contain all the determinants of host-pathogen interactions and possible drug
      targets, computational tools for selecting suitable candidates for further
      experimental analyses are currently limited. Detection of bacterial genes that
      are non-homologous to human genes, and are essential for the survival of the
      pathogen represents a promising means of identifying novel drug targets. We have
      used three-way genome comparisons to identify essential genes from Pseudomonas
      aeruginosa. Our approach identified 306 essential genes that may be considered as
      potential drug targets. The resultant analyses are in good agreement with the
      results of systematic gene deletion experiments. This approach enables rapid
      potential drug target identification, thereby greatly facilitating the search for
      new antibiotics. These results underscore the utility of large genomic databases
      for in silico systematic drug target identification in the post-genomic era.

PMID- 15724286
TI  - Curvature distribution in prokaryotic genomes.
AB  - DNA curvature is known to play a biological role in gene regulation, in
      particular, initiation of transcription. We applied the software CURVATURE based
      on the wedge model to predict whether promoter regions of certain prokaryotes may
      be characterized by higher intrinsic DNA curvature located within or upstream to
      these regions. The main purpose was to verify our earlier hypothesis that the DNA
      curvature plays a biological role in gene regulation in mesophilic as compared to
      hyperthermophilic prokaryotes, i.e., DNA curvature presumably has a functional
      adaptive significance determined by temperature selection. Therefore, we analyzed
      all available complete prokaryotic genomes. The analysis showed that there is a
      group of genomes with a relatively high average DNA curvature upstream of start
      of genes. Remarkably, all organisms of this group appeared to be mesophilic,
      which is a full confirmation of the former hypothesis. The conservative patterns
      of genomic curvature distribution across different mesophilic bacterial and
      archaeal genomes presented in this study provide a new, convincing indication
      that curved DNA is evolutionarily preserved and determined by temperature
      selection. Moreover, we found a rather peculiar property of hyperthermophilic
      prokaryotes: the coding regions are predicted to be significantly more curved
      than it would be expected from their dinucleotide composition.

PMID- 15724287
TI  - Thermo-search: lifestyle and thermostability analysis.
AB  - Thermo-search is an online web tool for the analysis of proteomes and individual
      proteins according to the ratio of two couplets of preferred and avoided amino
      acids in hyperthermophiles, thermophiles and mesophiles. It displays the ratio
      between glutamic acid plus lysine (E+K) and glutamine plus histidine (Q+H), which
      is higher in thermophilic proteomes and thermostable proteins than in mesophilic
      proteomes and thermo labile proteins. Thermo-search allows a rapid screen of the
      CRM database for thermostable proteins in their functional categories and a
      visualization of the (E+K)/(Q+H) average ratio between organisms, allowing a
      comparison of their lifestyles.

PMID- 15724288
TI  - Local backbone structure prediction of proteins.
AB  - A statistical analysis of the PDB structures has led us to define a new set of
      small 3D structural prototypes called Protein Blocks (PBs). This structural
      alphabet includes 16 PBs, each one is defined by the (phi, psi) dihedral angles
      of 5 consecutive residues. The amino acid distributions observed in sequence
      windows encompassing these PBs are used to predict by a Bayesian approach the
      local 3D structure of proteins from the sole knowledge of their sequences.
      LocPred is a software which allows the users to submit a protein sequence and
      performs a prediction in terms of PBs. The prediction results are given both
      textually and graphically.

PMID- 15724289
TI  - About an unusual case: GC-MS detection of lidocaine.
AB  - A man suspected to be a drug user was found dead; toxicological analysis of his
      biological samples showed the presence of lidocaine in all samples analysed,
      while cocaine was found only in the blood, urine and hair samples. We found that
      the cause of death was determined by ventricular arrhythmia associated to
      lidocaine/cocaine overdosage.

PMID- 15724290
TI  - Legends and secrets of telecommunications.

PMID- 15724291
TI  - International perspectives on forensic DNA databases.

PMID- 15724292
TI  - SNP typing strategies.
AB  - Single nucleotide polymorphism (SNP) typing is likely to be an adjunct forensic
      technology to be used when short tandem repeat (STR) typing fails to yield a
      result or when only a partial profile is obtained. It is anticipated that
      forensic SNP analyses will be applied to typing mtDNA, Y chromosome lineage
      analyses, characterizing highly degraded DNA samples, assessing biogeographical
      ancestry, and typing for determining physical characteristics. As examples, three
      SNP typing strategies are briefly described. They are SNaP shot, SNPstream Ultra
      High Throughput System, and electrospray ionization mass spectrometry. The latter
      approach offers certain advantages for SNP analyses, particularly so for mtDNA
      typing.

PMID- 15724293
TI  - The role of DNA technology in identification of skeletal remains discovered in
      mass graves.

PMID- 15724294
TI  - New developments and challenges in the use of the UK DNA Database: addressing the
      issue of contaminated consumables.

PMID- 15724295
TI  - Identification of the microvariant allele D7S820*9.2 in Armenian population.

PMID- 15724296
TI  - Terrorism and terrorist.

PMID- 15724297
TI  - Forensic fields of odonto-stomatology: a practical approach.

PMID- 15724298
TI  - Strategies and investigations for the defending counsel at the scene of the
      crime.

PMID- 15724299
TI  - The role of the expert, of the technical consultant and of the consultant for the
      defensive investigations in the criminal trial.

PMID- 15724300
TI  - Trial--unknown accused--defense warranty.

PMID- 15724302
TI  - Bibliography. Current world literature. Circulation and hemodynamics.

PMID- 15724301
TI  - Proceedings of the International Congress on Colorectal Cancer (ICCRC). May 28
      30, 2004. Chalkidiki, Greece.

PMID- 15724303
TI  - Abstracts of the Fourth International Conference on Cancer-Induced Bone Diseases.
      December 7-9, 2003. San Antonio, Texas, USA.

PMID- 15724304
TI  - Theoretic surgery - a scientific journal from cells to clinical guidelines. A
      Festschrift dedicated to Wilfried Lorenz on the occasion of his retirement.

PMID- 15724305
TI  - Facilitating attachment between school-aged children and a dying parent.
AB  - A qualitative, community study of 58 parentally bereaved children and their 35
      surviving parents illustrates how families take advantage of forewarning of death
      to foster connections between children and dying parents and prepare for
      youngsters' continued attachment to dying parents after the death. Children and
      parents displayed strong yearnings to remain connected during terminal illness,
      but fostering connections for attachment after the death was less intuitive and
      more emotionally fraught as it undermined coping strategies based on denial of
      impending death. Thus, although some may benefit from interventions aimed at
      anticipatory relationship facilitation, clinicians should respect limitations on
      what family members are psychologically able to bear.

PMID- 15724306
TI  - Acceptability for French people of physician-assisted suicide.
AB  - Our aim was to understand better how people judge the acceptability of physician
      assisted suicide (PAS). We found that, for people in France of all ages and for
      elderly people with life-threatening illnesses, acceptability is an additive
      combination of the number of requests for PAS, the patient's age, the amount of
      physical suffering, and the degree of curability of the illness, not only when
      judging for hypothetical patients, but also for their spouses and for themselves.
      PAS can be highly acceptable to people even when the patient does not satisfy all
      the criteria of legislation about PAS.

PMID- 15724308
TI  - Pharmaceuticals issue brief: pharmaceuticals cost control: year end report--2004.

PMID- 15724309
TI  - Pharmaceuticals issue brief: pharmaceutical assistance programs: year end report-
      2004.

PMID- 15724310
TI  - Pharmaceuticals issue brief: generic and therapeutic substitution: year end
      report--2004.

PMID- 15724311
TI  - Obituary: Lewis B. Sheiner, M.D.

PMID- 15724313
TI  - Developing and evaluating the GriefLink web site: processes, protocols, dilemmas
      and lessons learned.
AB  - Despite a profusion of recommendations regarding the quality of web sites and
      guidelines related to ethical issues surrounding health-related sites, there is
      little guidance for the design and evaluation of sites relating to loss and
      grief. This article, which addresses these deficiencies, results from a community
      consultation process of designing and evaluating a web site--GriefLink--for
      bereaved consumers and for the professionals who help them. It presents the
      literature review that informed the project, the recommendations for design and
      content, the lessons learned through the process itself, and the difficulties of
      evaluating the benefits of a grief-related web site. Some ethical and legal
      dilemmas in developing grief-related web sites are discussed and issues of
      design, content, process, evaluation, and general features are addressed, which
      may also be applied to other communication forms for loss and grief matters, such
      as the print media.

PMID- 15724314
TI  - Lessons from Jing.

PMID- 15724315
TI  - Breast MRI for management of patients with locally advanced breast cancer who are
      being referred for neoadjuvant chemotherapy.

PMID- 15724316
TI  - Magnetic resonance imaging of the breast for preoperative evaluation in patients
      with localized breast cancer.

PMID- 15724318
TI  - Customizing jobs for people with disabilities.

PMID- 15724317
TI  - An update on Medicare beneficiary access to physician services.
AB  - After declining markedly between 1997 and 2001, Medicare seniors' access to
      physician care stabilized between 2001 and 2003, according to a national study by
      the Center for Studying Health System Change (HSC). Access to care trends were
      parallel for Medicare seniors 65 and older and privately insured people between
      the ages of 55 and 64--the near-elderly--suggesting that health system
      developments were much more important influences on beneficiary access than any
      effects of Medicare's 2002 physician payment rate reduction. In addition, access
      to care for both Medicare seniors and privately insured near-elderly people was
      comparable in local health care markets where commercial insurance payment rates
      far exceed Medicare's. However, both Medicare seniors and older privately insured
      people waited longer for physician appointments.

PMID- 15724319
TI  - Online enrollment in Medicaid and SCHIP.

PMID- 15724320
TI  - Commission chief says trusts can't treat 'health check' as a project.

PMID- 15724321
TI  - New age of targets feared under 'intensive regime'.

PMID- 15724322
TI  - On out-of-hours care provision.

PMID- 15724324
TI  - On smoking cessation.

PMID- 15724323
TI  - The HSJ debate. Should we stop copying the US? For and against.

PMID- 15724325
TI  - Regional focus: London. Skill-mix beats the big-city blues.

PMID- 15724326
TI  - Polio postponed. Politics slow polio's eradication--and cause it to spread.

PMID- 15724327
TI  - A bad fix for hubble? Robotic repair may be riskier than first thought.

PMID- 15724328
TI  - Sound findings. Sonar offers a way to count salmon accurately.

PMID- 15724330
TI  - A glimpse of supersolid. Solid helium can behave like a superfluid.

PMID- 15724329
TI  - Through Titan's haze. Saturn moon has a surface that is dynamic--and puzzling.

PMID- 15724331
TI  - Snaking its way in. Feared snakehead fish sets up house in the U.S.

PMID- 15724332
TI  - Nurses in short supply. The profession is heading toward its biggest crisis.

PMID- 15724333
TI  - Quantum quackery. A hit film justifies hogwash with quantum mechanics.

PMID- 15724334
TI  - You, robot. Hans Moravec of Carnegie Mellon University aspires for robots to be
      humanity's successors.

PMID- 15724335
TI  - Immunity's early-warning system.

PMID- 15724336
TI  - The midlife crisis of the cosmos.

PMID- 15724337
TI  - Considerate computing.

PMID- 15724338
TI  - Capturing a killer flu virus.

PMID- 15724340
TI  - Best-kept secrets. Ouantum cryptography has marched from theory to laboratory to
      real products.

PMID- 15724339
TI  - Eye of the beholder. Wonders under the lens of the optical microscope.

PMID- 15724342
TI  - Keyless entry. Open sesame.

PMID- 15724343
TI  - How do computer hackers "get inside" a computer?

PMID- 15724341
TI  - Exploding the self-esteem myth.

PMID- 15724344
TI  - A randomized double-blind controlled trial comparing extra virgin coconut oil
      with mineral oil as a moisturizer for mild to moderate xerosis.
AB  - BACKGROUND: Xerosis is a common skin condition (1) characterized by dry, rough,
      scaly, and itchy skin, (2) associated with a defect in skin barrier function, and
      (3) treated with moisturizers. People in the tropics have effectively used
      coconut oil as a traditional moisturizer for centuries. Recently, the oil also
      has been shown to have skin antiseptic effects. A moisturizer with antiseptic
      effects has value, but there are no clinical studies to document the efficacy and
      safety of coconut oil as a skin moisturizer. OBJECTIVE: This study aimed to
      determine the effectivity and safety of virgin coconut oil compared with mineral
      oil as a therapeutic moisturizer for mild to moderate xerosis. METHODS: A
      randomized double-blind controlled clinical trial was conducted on mild to
      moderate xerosis in 34 patients with negative patch-test reactions to the test
      products. These patients were randomized to apply either coconut oil or mineral
      oil on the legs twice a day for 2 weeks. Quantitative outcome parameters for
      effectivity were measured at baseline and on each visit with a Corneometer CM825
      to measure skin hydration and a Sebumeter SM 810 to measure skin lipids. For
      safety, transepidermal water loss (TEWL) was measured with a Tewameter TM210, and
      skin surface hydrogen ion concentration (pH) was measured with a Skin pH Meter
      PH900. Patients and the investigator separately evaluated, at baseline and at
      each weekly visit, skin symptoms of dryness, scaling, roughness, and pruritus by
      using a visual analogue scale and grading of xerosis. RESULTS: Coconut oil and
      mineral oil have comparable effects. Both oils showed effectivity through
      significant improvement in skin hydration and increase in skin surface lipid
      levels. Safety was demonstrated through no significant difference in TEWL and
      skin pH. Subjective grading of xerosis by the investigators and visual analogue
      scales used by the patients showed a general trend toward better (though not
      statistically evident) improvement with coconut oil than with mineral oil. Safety
      for both was further demonstrated by negative patch-test results prior to the
      study and by the absence of adverse reactions during the study. CONCLUSION:
      Coconut oil is as effective and safe as mineral oil when used as a moisturizer.

PMID- 15724345
TI  - Quality of life of patients with allergic contact dermatitis: an exploratory
      analysis by gender, ethnicity, age, and occupation.
AB  - BACKGROUND: Little has been published regarding the impact of gender, ethnicity,
      age, and occupation on the quality of life (QoL) of patients with allergic
      contact dermatitis (ACD). OBJECTIVES: This study investigated the relationship
      between QoL scores for patients with ACD and variables such as gender, ethnicity,
      age, and occupation. METHODS: Four hundred twenty-eight patients with ACD were
      mailed a QoL questionnaire modified from Skindex-16 to include an additional five
      items pertaining to occupational impact. The QoL scores were analyzed to
      ascertain factors that affect QoL in patients with ACD. RESULTS: The response
      rate was 35%. Non-Caucasians reported lower QoL scores than did Caucasians within
      the functioning scale. There were no statistically significant gender-related
      differences in QoL scores although females reported a higher degree of emotional
      distress. Younger subjects were more likely to have lower QoL scores within the
      functioning and occupational scales. Industrial workers reported the worst
      occupational QoL, followed by office workers. Occupation was the variable that
      significantly affected the greatest number of survey subjects, followed by age,
      ethnicity, and gender. CONCLUSIONS: Three of the four variables examined had a
      significant association with QoL. Non-Caucasians, younger subjects, and
      industrial workers reported a significantly worse QoL due to ACD. There were no
      statistically significant gender-related differences in QoL scores.

PMID- 15724346
TI  - Contact dermatitis of the feet: a study of 53 cases.
AB  - BACKGROUND: Contact dermatitis of the feet is a common dermatosis that very often
      makes patients unable to perform daily activities. The differential diagnosis
      should be made with other dermatoses, such as tinea, atopic dermatitis,
      psoriasis, dyshidrosis, and nummular eczema. It is clinically difficult to
      establish a true diagnosis of contact dermatitis, and the results of epicutaneous
      tests may not be definite. However, studies undertaken to identify the etiologic
      agent may lead to a cure for patients. OBJECTIVES AND METHODS: The objectives of
      this study were (1) to verify the frequency of contact dermatitis of the feet
      among a group of patients seen at a public clinic, (2) to determine the type of
      contact dermatitis, and (3) to determine the most common sensitizers. We selected
      only patients with eczematous dermatitis from among 1,027 patients at the clinic,
      and they were patch tested with the Brazilian series. RESULTS: Of 1,027 patients
      who submitted to patch tests, 53 (5.2%) presented with dermatosis of the feet.
      Out of these 53 patients, 37 (70%) had at least one positive patch-test reaction,
      and the remaining 16 (30%) had negative results. CONCLUSION: The presence of
      dermatosis on the dorsal region of the foot in the majority of the patients with
      a positive test result was statistically significant (chi2 = 6.02; p < .05). The
      compounds that caused positive tests more often were rubber-vulcanizing agents,
      followed by metals and topical medications. The epicutaneous tests were found to
      be indispensable for the etiologic diagnosis of contact dermatitis of the feet.

PMID- 15724347
TI  - Contact allergic reactions of the vulva: a 14-year review.
AB  - BACKGROUND: In women with vulval complaints, irritant contact dermatitis is more
      common than allergic contact dermatitis, but secondary sensitization has to be
      taken into consideration since these patients often use several topical
      medications. OBJECTIVE: The aims of this retrospective study were to establish
      the prevalence of allergic contact dermatitis in patients with vulval complaints
      and to verify how many patients with allergic contact dermatitis suffered from a
      previous pathology. METHODS: We reviewed patch- and prick-test results from 92
      women. The women had all been administered the European Standard series, and most
      had also been tested for other allergens such as the ingredients of topical
      pharmaceutical products and cosmetics. RESULTS: Thirty-five patients (38%)
      presented with one or more positive allergic reactions. For 15 of the patients,
      these reactions were considered to be relevant to their clinical condition and
      were most often due to contact dermatitis from topical pharmaceutical products.
      Three patients presented with positive and relevant contact urticaria syndrome
      from latex, and two patients presented with protein contact dermatitis from human
      seminal plasma. CONCLUSION: Patients with vulval dermatitis are at risk of
      developing contact sensitivities, particularly to topical pharmaceutical
      products; therefore, attention should be paid to this problem when such products
      are prescribed.

PMID- 15724348
TI  - Pesticide patch test series for the assessment of allergic contact dermatitis
      among banana plantation workers in panama.
AB  - BACKGROUND: Irritant contact dermatitis and allergic contact dermatitis (ACD) are
      frequent among agricultural workers and require targeted interventions. Patch
      testing is necessary for differential diagnosis, but patch testing with
      pesticides is uncommon. OBJECTIVE: This study explores the frequency of ACD and
      sensitization to pesticides among highly exposed banana plantation workers.
      METHODS: Frequently and recently used pesticides on banana plantations in Divala,
      Panama, were documented. A pesticide patch test tray specific for this population
      was prepared. A structured interview was administered to 366 participants,
      followed by a complete skin examination. The pesticide patch test series, as well
      as a standard patch test series, was applied to 37 workers with dermatoses likely
      to be pesticide related and to 23 control workers without dermatoses. RESULTS:
      The pesticide patch tests identified 15 cases (41%) of ACD (20 positive
      reactions) among the 37 workers diagnosed with pesticide dermatosis. Three
      controls had allergic reactions to pesticides (4 positive reactions). The
      pesticides were carbaryl (5 cases), benomyl (4 cases), ethoprophos (3),
      chlorothalonil (2), imazalil (2), glyphosate (2), thiabendazole (2), chlorpyrifos
      (1), oxyfluorfen (1), propiconazole (1), and tridemorph (1). Ethoprophos and
      tridemorph had not been previously identified as sensitizers. Thus, the
      prevalence of ACD was 0.03 (15 of 366). On the basis of observed prevalences of
      positive patch-test reactions among the subgroups with and without dermatoses, we
      estimated that > or = 16% of the entire population may be sensitized to
      pesticides. CONCLUSION: Sensitization to pesticides among banana plantation
      workers is a frequent occupational health problem. Pesticide patch test trays
      should be used in assessing skin diseases in highly exposed workers.

PMID- 15724349
TI  - Allergic contact dermatitis from cocamidopropyl betaine, cocamidoamine, 3
      (dimethylamino)propylamine, and oleamidopropyl dimethylamine: co-reactions or
      cross-reactions?
AB  - We present the case of a patient with facial dermatitis caused by sensitization
      to cocamidopropyl betaine. The patient also had positive patch-test reactions to
      cocamidoamine, 3-(dimethylamino)propylamine, and oleamidopropyl dimethylamine.
      The presence of 3-(dimethylamino)propylamine as an impurity in all of these
      substances can be hypothesized to explain these simultaneous reactions.

PMID- 15724350
TI  - Allergic contact dermatitis from isocyanates among sculptors.
AB  - Allergic contact dermatitis from isocyanates is rare. We present the cases of two
      sculptors who developed a dermatitis from polyurethane sculpting materials. The
      patients reacted to diphenylmethane diisocyanate and isophorone diisocyanate. One
      of the patients had positive patch-test reactions to 1,6-hexamethylene
      diisocyanate and toluene diisocyanate as well. The patients also exhibited a
      sensitivity to diaminodiphenylmethane, an amine that has been reported in other
      cases of isocyanate sensitivity.

PMID- 15724351
TI  - Cutaneous and oral eruption from oral exposure to nickel in dental braces.
AB  - Oral eruptions due to nickel allergy are rare. A common presentation of intraoral
      contact dermatitis is the presence of lichenoid plaques on the buccal mucosa
      adjacent to the offending antigen. We report an unusual case of cutaneous and
      mucosal nickel allergy arising after placement of dental braces. An 11-year-old
      boy was referred by his orthodontist to the University of Minnesota Occupational
      and Contact Dermatitis Clinic to be evaluated for a possible metal allergy. The
      patient developed an itchy rash on his abdomen and under his wristwatch 1 week
      after dental braces were placed. He was diagnosed with allergic contact
      dermatitis from nickel. The patient avoided cutaneous nickel exposure and had a
      minimal resolution of his symptoms. One year later, the patient developed
      swelling and burning of the lips. Secondary to extreme discomfort, the braces,
      which contained nickel, titanium, and zinc, were removed. The patient underwent
      standard patch testing; the final reading at 96 hours showed a +++ reaction to
      nickel, palladium, cobalt chloride, and neomycin. The patient experienced relief
      of his oral symptoms after removal of the braces. No current relevance to
      palladium, cobalt, or neomycin has been found.

PMID- 15724352
TI  - Efficacy of tacrolimus ointment in the prevention and treatment of contact
      dermatitis.

PMID- 15724353
TI  - Corneal haze coincident with poison ivy dermatitis months after photorefractive
      keratectomy.

PMID- 15724354
TI  - Allergic contact sensitization from intravesical mitomycin C, without dermatitis.

PMID- 15724355
TI  - Interpret moisture studies with care.

PMID- 15724356
TI  - The effect of ageing on the recollection of emotional and neutral pictures.
AB  - This study investigated age-related differences in recognition memory for
      emotional and neutral pictures. Younger and older participants were asked to rate
      pictures according to their emotional valence, arousal, and visual complexity.
      Two weeks later they had to recognise these pictures and the states of awareness
      associated with memory were assessed with the "remember/know/guess" paradigm. We
      found that, although the influence of emotion on recognition accuracy (as
      assessed by d') was similar in both age groups, the tendency for positive and
      negative pictures to create a rich recollective experience was weaker in older
      adults. In addition, "remember" responses were more often based on a recollection
      of emotional reactions in older than in younger participants. We suggest that the
      elderly tend to focus on their feelings when confronted with emotional pictures,
      which could have impaired their memory for the contextual information associated
      with these stimuli.

PMID- 15724357
TI  - Organisation and retrieval: the generation of event clusters.
AB  - The present research examined the nature of autobiographical memory event
      clusters. Specifically we were interested in the interplay between the content
      and organisation of autobiographical memory with retrieval in determining the
      similarity of event memories across time. Using an event cueing procedure,
      clusters of related event memories were generated. Participants sorted these
      events into meaningful groups after a delay of several weeks. The results suggest
      that participants' ability to perform this sorting task is dependent on their
      ability to reinstate the retrieval context. Further our results suggest that
      event clusters are chains of related event memories as opposed to clusters of
      interrelated event memories.

PMID- 15724358
TI  - Changing scenes: memory for naturalistic events following change blindness.
AB  - Research on scene perception indicates that viewers often fail to detect large
      changes to scene regions when these changes occur during a visual disruption such
      as a saccade or a movie cut. In two experiments, we examined whether this
      relative inability to detect changes would produce systematic biases in event
      memory. In Experiment 1, participants decided whether two successively presented
      images were the same or different, followed by a memory task, in which they
      recalled the content of the viewed scene. In Experiment 2, participants viewed a
      short video, in which an actor carried out a series of daily activities, and
      central scenes' attributes were changed during a movie cut. A high degree of
      change blindness was observed in both experiments, and these effects were related
      to scene complexity (Experiment 1) and level of retrieval support (Experiment 2).
      Most important, participants reported the changed, rather than the initial, event
      attributes following a failure in change detection. These findings suggest that
      attentional limitations during encoding contribute to biases in episodic memory.

PMID- 15724359
TI  - Mixed- versus strong right-handedness is associated with biases towards
      "remember" versus "know" judgements in recognition memory: role of
      interhemispheric interaction.
AB  - Growing evidence supports the hypothesis that episodic versus semantic memories
      rely primarily on interhemispheric versus intrahemispheric processing,
      respectively. For example, a recent study found that individuals with presumed
      greater interhemispheric interaction were superior in episodic recall but
      inferior at semantic word fragment completion; however, tests of recognition
      memory yielded no group differences. Interestingly, recognition memory can be
      based on either explicitly remembering a stimulus or implicitly knowing that a
      stimulus had been presented. The current experiments administered recognition
      memory tests to strongly versus mixed handed participants who judged for each
      recognised item whether their response was based on remembering (episodic memory)
      or knowing (semantic memory) (Tulving, 1983). Results indicate that strong versus
      mixed handers are biased towards basing recognition responses on judgements of
      knowing versus remembering, respectively. As strong versus mixed handedness is
      associated with greater versus lesser interhemispheric processing, the results
      support the original hypothesis.

PMID- 15724360
TI  - Stability in autobiographical memories.
AB  - A total of 30 undergraduates recalled the same 20 autobiographical memories at
      two sessions separated by 2 weeks. At each session they dated their memories and
      rated them on 18 properties commonly studied in autobiographical memory
      experiments. Individuals showed moderate stability in their ratings on the 18
      scales (r approximately .5), with consistency of dating being much higher (r =
      .96). There was more stability in the individuals' average rating on each scale
      (r approximately .8), even when the averages were calculated on different
      memories in the different sessions. The results are consistent with a
      constructive view of autobiographical memory, in which stable individual
      differences in cognitive style are important.

PMID- 15724361
TI  - Does test delay eliminate collaborative inhibition?
AB  - Earlier research has demonstrated that collaborative groups recall more than
      individuals, but less than nominal groups (pooled performance of individuals),
      thus exhibiting collaborative inhibition. In two experiments, all participants
      were first asked to recall story material on their own. Some participants were
      then assigned to pairs and recalled the material collaboratively. On the other
      hand, the participants in the individual recall condition were asked to recall
      the material once again on their own. In Experiment 1, the collaborative pairs
      recalled less than the nominal pairs in accordance with previous studies. In
      Experiment 2, the timing of the initial individual recall was manipulated by
      inserting one week between the learning and the recall. The collaborative
      inhibition was eliminated in this situation. Sources of the collaborative
      inhibition in immediate recall and its disappearance in delayed recall are
      discussed in terms of the effect of cross cueing in collaborative remembering.

PMID- 15724362
TI  - Chunks in expert memory: evidence for the magical number four ... or is it two?
AB  - This study aims to test the divergent predictions of the chunking theory (Chase &
      Simon, 1973) and template theory (Gobet & Simon, 1996a, 2000) with respect to the
      number of chunks held in visual short-term memory and the size of chunks used by
      experts. We presented game and random chessboards in both a copy and a recall
      task. In a within-subject design, the stimuli were displayed using two
      presentation media: (a) physical board and pieces, as in Chase and Simon's (1973)
      study; and (b) a computer display, as in Gobet and Simon's (1998) study. Results
      show that, in most cases, no more than three chunks were replaced in the recall
      task, as predicted by template theory. In addition, with game positions in the
      computer condition, chess Masters replaced very large chunks (up to 15 pieces),
      again in line with template theory. Overall, the results suggest that the
      original chunking theory overestimated short-term memory capacity and
      underestimated the size of chunks used, in particular with Masters. They also
      suggest that Cowan's (2001) proposal that STM holds four chunks may be an
      overestimate.

PMID- 15724363
TI  - The role of rehearsal and generation in false memory creation.
AB  - The current research investigated one possible mechanism underlying false
      memories in the Deese-Roediger-McDermott (DRM) paradigm. In the DRM paradigm,
      participants who study lists of related words (e.g., "table, sitting, bench ...")
      frequently report detailed memories for the centrally related but non-presented
      critical lure (e.g., "chair"). One possibility is that participants covertly call
      to mind the critical non-presented lure during the study phase, and later
      misattribute memory for this internally generated event to its external
      presentation. To investigate this, the DRM paradigm was modified to allow
      collection of on-line thoughts during the study phase. False recognition
      increased following generation during study. False recognition also increased
      following study of longer lists; this effect was partially explained by the fact
      that longer lists were more likely to elicit generations of the critical lure
      during study. Generation of the lure during study contributes to later false
      recognition, although it does not explain the entire effect.

PMID- 15724364
TI  - Data mapping for HIPAA transactions.

PMID- 15724365
TI  - Danger, danger: compliance documentation as a weapon.

PMID- 15724366
TI  - Biometric authentication: privacy protection or invasion?

PMID- 15724367
TI  - Writing a coding success story: best practices and beyond. Panel discussion.
AB  - What are the cornerstones of a thriving coding department? How can you ensure
      your coding team is built on a foundation of education, compliance, and
      satisfaction? We spoke with several coding managers to collect solutions and
      guidance for common coding challenges.

PMID- 15724368
TI  - Know your APCs: data analysis made simple.
AB  - You've adapted processes to the APC system, but do you really understand the
      financial impact of APCs on your organization? The author shows you how to
      analyze your billing data to assess the impact of APCs on your facility's bottom
      line.

PMID- 15724369
TI  - Solving the E/M conundrum: a special report. Navigating the physician services
      maze.

PMID- 15724370
TI  - Solving the E/M conundrum: a special report. E/M options in the outpatient arena.

PMID- 15724371
TI  - SNOMED takes the next step.
AB  - Healthcare terminologies SNOMED and the Read Codes have been around for a long
      time. Now, a new terminology combining the two promises to take the industry one
      step closer to realizing the vision of an electronic patient record. Here 's a
      sneak peek at SNOMED CT.

PMID- 15724372
TI  - Can you manage managed care?
AB  - HIM professionals' data management skills make them a hot property in many
      settings, but none more so than managed care. In this second installment of the
      Journal of AHIMA's special series on managed care, the author describes the ways
      managed care organizations use data and how HIM professionals can contribute.

PMID- 15724374
TI  - Professional practice solutions.... It's difficult to research and write
      organizational policies because of the myriad external forces governing the same
      healthcare issues. Do you have any guidelines to help ensure we don't miss any
      mandates?

PMID- 15724373
TI  - DRG analysis reveals potential problems, trends.
AB  - Specific DRGs are frequently the targets of review if they are connected to
      errors. But documentation review alone to identify problems may not be
      sufficient. The author describes a strategy to review aggregate data for two
      tricky DRGs.

PMID- 15724375
TI  - An update on Joint Commission core measures.

PMID- 15724376
TI  - Crossing the terrain between you and your goals.

PMID- 15724377
TI  - The latest look at coding trends.

PMID- 15724378
TI  - New anemia codes address chronic illness.

PMID- 15724379
TI  - Tackling backlogs and hurdles.

PMID- 15724380
TI  - Telomerase activity in Philadelphia positive chronic myeloid leukaemia.
AB  - Telomerase is a specialized type of reverse transcriptase that catalyzes the
      synthesis and extension of telomeric DNA. Activation of telomerase and
      stabilization of telomeres are considered necessary for immortalization of tumor
      cells. Chronic Myeloid Leukaemia (CML) is a good example to investigate the
      reactivation of telomerase as; after a variable period in chronic phase, CML
      undergoes further evolution. The aim of this work is to study telomerase activity
      in patients with philadelphia- positive CML and to compare the relative amount of
      telomerase activity between chronic phase, accelerated phase and blastic crisis.
      The study is conducted on 3 groups. Group I comprised ten newly diagnosed CML
      patients in chronic phase; five males and five females their ages ranged from 24
      63 years (X = 44.1 +/- 11.2 years). Group II comprised ten patients in acute
      transformation (accelerated or blastic crisis phase); seven were males and three
      were females their ages ranged from 14 to 63 years ( X = 35.7 +/- 16.2 years).
      Ten healthy subjects comprised the control group III; five males and five females
      their ages ranged from 14-50 years ( X = 31.8 +/- 12.4 years). All patients were
      subjected to thorough history taking and clinical examination, complete blood
      picture with differential cell counts, bone marrow aspiration and/or biopsy,
      neutrophil alkaline phosphatase scoring by cytochemistry, immunophenotyping to
      identify the type of blast crisis, chromosomal analysis to detect Ph-positive
      cases, and measurement of telomerase activity by PCR-ELISA technique. Telomerase
      activity was highest in acute transformation with a range of (0.252-1.896) and
      mean of 1.521 0.496, while in chronic phase ranged between 0.67 and 0.743 with a
      mean of 0.305 +/- 0.109 and in normal controls the range was 0.45 to 0.195 with a
      mean of 0.102 +/- 0.048. The difference between groups was statistically
      significant. No correlation was found between the activity of the telomerase and
      hemoglobin, platelet, leucocyte counts, percentage of peripheral blood, bone
      marrow blasts, basophils, bone marrow cellularity, the type of crisis as well as
      leucocyte alkaline phosphatase scoring. In conclusion; The increased level of
      telomerase activity as noticed in the different stages of CML indicates its
      association with disease progression and can be used as a useful marker for
      evaluating development of the course.

PMID- 15724381
TI  - The production and evaluation of a standard diagnostic peste des petits ruminants
      (PPR) hyperimmune serum prepared from the Egyptian antigen (Egypt 87).
AB  - The aim of this study was to produce a specific hyperimmune serum for diagnosis
      of peste des petits ruminants (PPR). Based on good laboratory practices and
      standard operating procedures, we produced this reagent in goats using attenuated
      local strain of PPRV. The quality was assured to meet the internationally
      required levels of potency and sterility. The titer of the product was 1024 as
      evaluated by virus neutralization (VN) and agar gel immunodiffusion (AGID) tests.
      In its final form, it is a sterile disc of a lyophilized material with a pale
      yellow colour, placed into an evacuated, tightly capped and capsulated vial.
      Local availability of such a product could be of great benefit at the time of
      need.

PMID- 15724383
TI  - Different cytokine patterns in patients coinfected with hepatitis C virus and
      Schistosoma mansoni.
AB  - Schistosoma mansoni (S. mansoni) and hepatitis C virus (HCV) coinfection is
      common in Egypt and other developing countries. Patients coinfected with HCV and
      schistosomiasis exhibit a unique clinical, virological and histological pattern
      manifested by viral persistence with high HCV RNA titers as well as higher
      necroinflammatory and fibrosis scores in their liver biopsy samples. Dual
      infections of schistosomiasis and viral infections display significant influences
      on host immune reactions including cytokine shift pattern alteration, cytotoxic T
      lymphocyte response and other impaired immunologic functions with diminished
      capacity to clear the virus. We investigated the cytokine pattern against HCV and
      S. mansoni antigens in patients coinfected with HCV and S. mansoni and compared
      them with responses in patients infected with HCV or S. mansoni alone. This study
      included 4 groups; (Gr I) included 20 patients infected with chronic HCV, their
      sera were reactive for anti-HCV antibodies, samples were verified for RNA
      detection to identify those who have viremia. (Gr II) included 15 patients
      infected with schistosomiasis alone, they were subjected to detection of S.
      mansoni ova in stool, rectal snip or serological test. (Gr III) included 20
      patients with chronic HCV and schistosomiasis coinfection, which were diagnosed
      by the above-mentioned criteria. (Gr IV) included 15 healthy individuals, who
      were matched for age and sex and have no evidence of liver diseases served as
      control subjects. The results showed that a highly significant increase in serum
      IFN-gamma and IL-18 levels in patients infected with HCV alone compared with the
      other patient groups and control. On the other hand, a highly significant
      increase was found in serum IL-4 and IL-10 levels in coinfected patients and
      patients with schistosomiasis alone compared with the control but a significant
      increase was found in the two groups compared with HCV patients. A significant
      increase in serum IL-4 and IL-10 were also found in HCV patients compared with
      the control. In conclusions, our data showed that coinfected patients have
      dominant Th2 cytokine profile induced by S. mansoni and this Th2 antagonized and
      down-regulated the antiviral activities of Th1 cytokine profile in HCV infection
      that probably acquired after S. mansoni infection resulting in failing to mount
      significant HCV specific Th1 response and thereby fail to clear the virus in
      coinfected, compared with patients infected with HCV or schistosomiasis alone.

PMID- 15724382
TI  - Local expression of tumor necrosis factor-alpha and interleukin-4 mRNA in
      different types of warts.
AB  - The natural history of warts shows considerable variations between individuals,
      ranging from spontaneous regression to prolonged persistence. The level of
      cytokines participate in the immune response to human papilloma virus. This work
      investigates local expression of T-helper1 (Th1)/ T-helper2 (Th2)/ cytokines in a
      trial to disclose the different immunological mechanisms affecting the natural
      history of warts. A total of thirty patients suffering from different types
      (common, plane, plantar and anogenital) of viral warts were included. An excision
      biopsy was used to assess tumor necrosis factor-alpha (TNF-alpha) and interleukin
      4 (IL-4) expression. Local expression of TNF-alpha (Th1) and IL-4 (Th2) in wart
      tissue was determined using in-situ hybridization technique. The cytokines probes
      used in this assay detect messenger RNA (mRNA) in wart tissue. Local expression
      of TNF-alpha mRNA was higher in viral wart patients compared to healthy control
      (P < 0.01), while local expression of IL-4 was not significantly higher in
      patients compared to control (P > 0.05). Statistical analysis was done to
      determine whether variations in cytokine mRNA expression depend on wart location
      or clinical types. In conclusion, immunoreactivity to warts is likely to be
      associated with a predominant Th-1 or mixed Th-1/ Th-2 cytokine mRNA expression
      profile. However, it does not appear to be a simple causal relationship between
      expression of a Th-1 pattern and clearance.

PMID- 15724384
TI  - Tumor necrosis factor alpha in patients with acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) is a myocardial necrosis occurring due to
      persistent coronary ischemia, in which inflammation plays an important role and
      heart failure is a common complication. The present work was undertaken to
      clarify the role of Tumor Necrosis Factor Alpha (TNF-alpha) in acute myocardial
      infarction (AMI). The study was conducted on 20 newly diagnosed AMI patients and
      10 healthy age and sex matched controls. Sequential estimation of plasma TNF
      alpha level was carried out at admission, 24 and 48 hours post admission using
      ELISA. AMI patients showed a significant increase of plasma TNF-alpha level on
      admission, and 24 hours post admission but not after 48 hours. However, a
      significant increase was still seen at 48 hours post admission in patients with
      signs of heart failure but not in those without signs of heart failure. A
      significant positive correlation was found between plasma TNF-alpha level and CPK
      level at admission. On the other hand a significant negative correlation was
      found between these 2 parameters at 24 and 48 hours post admission. It is
      concluded that TNF-alpha may be an early marker of myocardial damage because of
      the early increase of its level after ischemic injury instead of being late
      consequence of extensive tissue necrosis. TNF-alpha level may be an important
      indicator of the severity of AMI and the occurrence of heart failure.

PMID- 15724385
TI  - The role of oxidative products of nitrous oxide and the tumor necrosis factor
      alpha in dilated cardiomyopathy.
AB  - Dilated Cardiomyopathy (DCM) is a disease of the myocardium and one of the
      leading causes of death in patients with heart diseases. We explored the role of
      increased Nitric oxide and TNF-alpha on the pathogenesis and progression of DCM.
      25 patients with DCM, and 20 apparently healthy age and sex matched controls,
      were studied. Patients were divided into 2 groups according to the presence or
      absence of pulmonary hypertension. All patients and controls were subjected to
      full cardiological assessment including plain chest x-ray, 12 lead ECG, and
      thorough 2D and Doppler echocardiography study. Laboratory investigations
      included measurement of plasma nitrite, nitrate and TNF-alpha levels. Plasma
      nitrite, nitrate and TNF-alpha concentrations were significantly elevated in DCM
      patients as compared to controls, and the elevation correlated with the
      decreasing functional status of the patients. It is concluded that plasma
      nitrite, nitrate, and TNF-alpha levels in DCM are not only linked to the severity
      of heart failure at presentation and during follow up, but also to the worsening
      of left ventricular function as evidenced by the decrease in ejection fraction
      and increase in end systolic and diastolic ventricular diameters during the
      echocardiography evaluation.

PMID- 15724386
TI  - Avidity as a parameter for diphtheria vaccine efficacy.
AB  - The avidity of antibodies (Abs) to diphtheria Toxin (DT), toxoids (DTo) and the
      DT binding site (DTBS) was investigated in sera from guinea bigs vaccinated with
      various DTo. Measurement of avidity by the thiocyanate procedure revealed that,
      the maturation patterns of Abs to the corresponding DTo were not much different
      whereas the maturation patterns of Abs to DT were different. Differences up to 20
      folds were observed in the affinity to the DTBS as measured by the tissue culture
      procedure and expressed as equilibrium constant (K). The avidity of Abs to either
      the corresponding DTo or the DT could not be correlated to the vaccine efficacy,
      whereas the vaccine efficacy could be ranked according to its affinity to the
      DTBS. This may be explained in terms of the specificity of measurement in each
      procedure. The thiocyanate procedure measures the average avidity to complex
      antigens with several epitopes whereas the tissue culture procedure allows
      determination of the affinity of Abs to the DTBS. It is concluded that in
      assessment of new vaccines, attention should be given to including measurement of
      the avidity of Abs to known protective epitopes rather than to complex antigens
      or a mixture of antigens.

PMID- 15724387
TI  - Hepatitis C Virus and related changes in immunological parameters in non
      Hodgkin's lymphoma patients.
AB  - Viral hepatitis is a common and important problem in immunocompromised cancer
      patients. The present study was conducted to investigate changes in some cellular
      and humoral immunological parameters as a consequence of HCV infection in non
      Hodgkin's lymphoma patients (NHL). The study included 40 NHL patients: 20 anti
      HCV antibody positive (Gr. I ), and 20 anti-HCV antibody negative (Gr.II ). In
      addition, forty non-cancer controls (NCCs) were included: 20 of them were anti
      HCV antibody positive (Gr. III) and 20 anti-HCV antibody negative (Gr. IV). The
      studied immunological parameters included serum levels of interleukin-1 (IL-1),
      interleukin-2 (IL-2), interleukin-6 (IL-6), and soluble tumor necrosis factor
      receptors (s-TNFr) measured by ELISA, as well as assessment of T and B lymphocyte
      subsets by PAP immunostaining method. Mean IL-1 level (pg/ml) was significantly
      higher in Gr. 1 (14 +/- 6) and Gr. III (20 +/- 12) as compared to those in Gr. II
      (7 +/- 5) and Gr. IV (9 +/- 6). Mean IL-2 level (pg/ml) was also significantly
      higher in Gr. I (132 +/- 101) and Gr. III (135 +/- 59) compared to those in Gr.
      II (36 +/- 29) and Gr. IV (31 +/- 48). On the other hand, level of IL-6 showed no
      significant difference between groups. The mean level of sTNF-r, (ng/ml) was only
      significantly higher in Gr. I (2.9 +/- 1.7) when compared to that in Gr. IV (1.9
      +/- 2.2). In group IV, the average percentage of CD3 (70 +/- 4%) and CD4 (44 +/-
      5%) were significantly higher than in those of Gr. I (CD3 = 51 +/- 11%, CD4 = 30
      +/- 12%), Gr. II (CD3 = 52 +/- 7%, CD4 = 30 +/- 8%), and Gr. III (CD3 = 52 +/-
      9%, CD4 = 26 +/- 8%). From all the above immunological and virological features
      two main tips could be inferred: (1) HCV leads a mild course of infection in NCCs
      evidenced by normal ALT level in all but 20% of subjects, normal IL-6, sTNF-r,
      lower counts of CD4+ T cells and hence a mild hepatocellular injury, and (2) In
      the immunocompromised NHL patients the virus leads potentially more aggressive
      course as evidenced by higher viremia, as well as significant elevation in sTNF
      r, and CD8+ depression.

PMID- 15724388
TI  - Characterization of three types of Schistosoma mansoni soluble egg antigen and
      determination of their immunodiagnostic potential by western blot immunoassay.
AB  - On the search of highly sensitive and specific antigenic components for use in
      serological tests, the serologic activities of the various protein fractions of
      three types of Schistosoma mansoni soluble egg antigen (SEA) were compared in an
      immunoblot analysis for their ability to detect schistosomiasis mansoni
      infections . Three types of soluble egg antigen (SEA) were prepared from three
      suspensions of Schistosoma mansoni eggs; namely living SEA (L-SEA), dead SEA (D
      SEA) and mixed SEA (M-SEA). The three antigens were resolved by sodium dodecyl
      sulphate polyacrylamide gel electrophoresis. A total of 80 Egyptian individuals
      were enrolled in the present study. After being screened by clinical examination,
      urine and stool analysis, sigmoidoscopy rectal snip examination, abdominal
      ultrasonography and indirect haemagglutination test (IHAT), the study population
      were grouped into an active intestinal schistosomiasis group (group I, n=20), a
      schistosomiasis seropositive group by IHA test (group II, n=20), a parasite
      control group including 10 patients with hydatidosis & 10 patients with
      fascioliasis (group III, n = 20) and a normal control group (group IV, n=20).
      Sera of all subjects were studied by immunoblotting for the presence of IgG
      antibodies against the various protein fractions of the three prepared types of
      SEA. Several protein bands from the 3 types of SEA reacted with the
      schistosomiasis patients' sera in a heterogenous manner. However, a 31-32 kilo
      daltons (kDa) protein fraction of L-SEA reacted with 80% (16/20) of group I sera,
      40% (8/20) of group II sera, one hydatidosis serum, but no reaction occurred with
      normal sera. Also, in the active intestinal schistosomiasis group, the 31-32 kDa
      fraction of L-SEA was more recognized by patients with early active intestinal
      schistosomiasis without organomegaly (100%, 12/12) than in those with
      organomegaly (50%, 4/8) (P < 0.05). On the other hand, a 80-82 kDa band of M-SEA
      was recognized by 70% (14/20) of group 1, 30% (6/20) of group II & sera from 3
      hydatidosis and 2 fascioliasis cases, but not by normal human sera. So, it can be
      concluded that the 31-32 kDa protein fraction of L-SEA is highly immunogenic,
      with the least cross reaction with other parasitic infections, and may be a
      useful serologic marker for diagnosing and differentiating between early and
      chronic schistosomiasis mansoni infection.

PMID- 15724389
TI  - Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and
      adult Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized
      by a large number of autoantigens and autoantibodies and infiltration of
      glandular tissue by predominantly CD4 T lymphocytes. The presence of certain
      autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA
      and anti-La/SSB. The aim of this study is to investigate the prevalence of anti
      alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult
      SS. Thirteen cases with juvenile SS and 11 old SS patients were examined.
      Selection and classification of the patients was based on the revised European
      Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age
      ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their
      age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte
      sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex
      agglutination test for estimating rheumatoid factor (RF) and antinuclear
      antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti
      La using ELISA. The two groups were matched for sex ratio. There was a
      significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both
      groups (P < 0.05). There was no statistically significant difference of levels of
      ESR, ANA and anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies
      concentration in the sera of SS patients in both groups (P > 0.05) although their
      levels were elevated. The percentage of detection of anti-Ro, anti- La and anti
      alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%,
      53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and
      81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS
      patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and
      IgA antibodies did not significantly correlated with antibodies against Ro and
      La, ESR and ANA (r < 0.25, P > 0.05). The detection of anti-alpha fodrin
      antibodies may prove to be a useful sensitive marker for SS. Routine screening of
      alpha fodrin antibodies is a valuable tool for the diagnosis of SS.

PMID- 15724390
TI  - The Bcl-2 and TGF-beta1 levels in patients with chronic hepatitis C, liver
      cirrhosis and hepatocellular carcinoma.
AB  - Relatively little is known about the biochemical mechanisms controlling
      proliferation and neoplastic transformation of Hepatocellular carcinoma (HCC).
      The aim of study was to determine the level of the oncoproteins Bcl-2,
      transforming growth factor-beta1 (TGF-beta1) and alpha fetoprotein (AFP) in serum
      of patients with chronic hepatitis C (CHC), and liver cirrhosis (LC) as compared
      to HCC as a biomarkers of malignant transformation and early detection of
      suspected patients. A total of forty-three patients were included, 30 of them
      were males and 13 females, their ages ranged from 29-66 years (49.37 +/- 8.35).
      Increased levels of Bcl-2 were found in liver cirrhosis and HCC groups as
      compared to CHC and control groups (P < 0.001). The level of Bcl-2 was higher in
      CHC than control but the difference was insignificant (P > 0.05). Serum TGF-beta1
      was significantly increased in CHC and liver cirrhosis groups as compared to HCC
      and control groups (p < 0.001). However, there was no significant difference
      between TGF-beta1 in HCC and control group (P > 0.05). The AFP level was
      significantly increased in HCC than CHC and liver cirrhosis. No significant
      difference was detected in AFP between CHC and LC patients (P > 0.05) or between
      CHC and healthy control (P > 0.05). A positive correlation was found between Bcl
      2, and AFP in LC and HCC groups. It is concluded that the increased level of Bcl
      2 in HCC may be involved in hepatocacingenesis. TGF-beta1 may be the primary
      marker to start the process of carcinogenesis, however, low level of TGF-beta1
      may be needed to the progress of malignancy.

PMID- 15724391
TI  - Evaluation of natural killer cells as diagnostic markers of early onset neonatal
      sepsis: comparison with C-reactive protein and interleukin-8.
AB  - This study was conducted on thirty-seven neonates and healthy neonates (sixteen
      full term and fourteen preterm). The study aimed at revealing the role played by
      the NK cells in neonatal sepsis and evaluating the sensitivity of NK cell number
      and cytotoxicity as diagnostic markers in infants with suspected early neonatal
      sepsis compared with the circulating cytokine IL-8 and CRP levels. All samples of
      peripheral blood lymphocytes were subjected to determination of CD16 and CD56
      positive cells using flow cytometry and NK cytotoxicity using the standard 4h
      51Cr release assay. Sera were separated to measure IL-8 using ELISA.
      Determination of CRP, using turbdimetric assay, as well as blood cultures were
      done for patient's group only. Out of the 37 cases of suspected early neonatal
      sepsis, 16 were given final diagnosis of sepsis. Seven infants (43.8%) in the
      sepsis group had culture-proven diagnosis, one of which had meningitis. The
      median CRP value was significantly higher in sepsis group (88 mg/L; range: 17-159
      mg/L) compared with that in non-septic group (15.4 mg/L; range: 7.6-23.2 mg/L, p
      < 0.001) only 12-60 h after admission. On the other hand, newborns in the sepsis
      group had significantly higher serum levels of IL-8 (median 310 pg/mL; range: 37
      583 pg/ml) at study entry than that in the non septic group (median 63 pg/mL;
      range: 32-94 pg/ml, P < 0.001). On admission, the NK activity, rather than the
      number of CD16 and CD56 positive cells was much affected where NK cytotoxicity
      was significantly lower in sepsis group (3.4 +/- 2.1%, range 0.9-7%) than that of
      the nonseptic group (18.3 +/- 6.7%: range 10.7- 25.3%, p < 0.01) and healthy
      neonates (23.8 +/- 4.7%: range 12.2-32.3%, p < 0.001). We may conclude that
      defective NK cell activity rather than NK cell number plays an important role in
      susceptibility to early onset neonatal sepsis. Evaluation of NK cytotoxicity as a
      marker in early diagnosis of neonatal sepsis reveals that the sensitivity,
      specificity and predictive values of reduced NK cytotoxicity (10% killing) was
      higher than both of CRP and IL-8, either individually or in combination.
      Additionally, reduced NK cytotoxicity showed high correlation with the severity
      and outcome of neonatal sepsis. Our data raise the possibility that the addition
      of NK cell activity to the standard work-up of critically ill patients with
      suspected sepsis could increase diagnostic certainty and generate an improved
      patient management.

PMID- 15724392
TI  - Application of refractory fragment amplification system for detection of Egyptian
      variant of Familial Mediterranean Fever.
AB  - Until recently, the diagnosis of familial Mediterranean fever (FMF) was, based on
      clinical manifestations, ethnicity, family history and response to colchicines.
      The aim of this study is to evaluate the use of polymerase chain reaction (PCR)
      for diagnosis of FMF and to detect the prevalence of the most common MEFV gene
      (FMF gene) mutations, M694V and V726A in FMF Egyptian patients. From January 2002
      to December 2002, twenty patients with FMF as well as 10 healthy subjects with no
      symptoms suggestive of FMF were enrolled in this study. All patients were
      subjected to PCR for MEEV gene mutations detection. Fifteen patients (75%) have
      age of onset of FMF less than 20 years. Five patients (25%) had past history of
      appendicectomy or laparotomy. The clinical features of patients during attacks
      were fever (100%), abdominal pain (95%), arthritis (55%), pleurisy (40%) and no
      skin rash or pericarditis. The M694V mutation was detected in 20 patients (100%)
      and V726A mutation in 17 patients (85%). No false positive or false negative
      results were obtained by using the three sets of primers for each sample,
      indicating a sensitivity and specificity of 100% of this assay.

PMID- 15724394
TI  - Recent approach for diagnosis of early HCV infection.
AB  - Detection of HCV infection during the window phase of infection, before
      seroconversion, is important in blood screening. However, a significant delay
      exists between the time of infection and the development of antibodies. The delay
      in window period can last up to 70 days. The aim of the present study was to
      investigate the kinetics of HCV markers during early infection, with detection of
      HCV core antigen as an early method for diagnosis. The study included
      determination of HCV RNA by qualitative and quantitative PCR, HCV core antigen
      detection by enzyme linked immunosorbent assay (ELISA) and specific serological
      markers including anti-HCV IgG and IgM. The study was carried out on 34 patients
      diagnosed as non A non B acute hepatitis and proved to be hepatitis C by
      qualitative HCV RNA PCR. Sixteen healthy control subjects were also included.
      From each consenting patient and control, blood samples were collected and serum
      was separated and subjected to determination of AST and ALT and the following
      virological laboratory tests: HCV core antigen detection by ELISA, determination
      of specific anti-HCV IgM and specific anti-HCV IgG, qualitative and quantitative
      determination of HCV RNA by second version of PCR. In patients, the median
      quantity of HCV RNA was 739.1 x 10(3) lu/ml with minimum quantity 2.1 x 10(3)
      lu/ml and maximum 38352.3 x 10(3) lu/ml. A comparison between the different
      diagnostic methods revealed that the highest sensitivity was for HCV-core antigen
      detection (82.4%), specificity was 100% negative predictive value was 72.2% and
      positive predictive value was 100%. Specific anti-HCV IgG had moderate levels of
      sensitivity (58.5%), specificity (75%), negative predictive value (46.2%)and
      positive predictive value (83.3%). The least sensitive method was the specific
      anti-HCV IgM (29.4%) with negative predictive value 40% but had specificity and
      positive predictive value of 100% of each. From this study we could conclude the
      followings: From virological methods, serological detection of specific IgM anti
      HCV had the least sensitivity limits, while it had the highest specificity and
      positive predictive value. Specific anti-HCV IgG had moderate sensitivity and
      specificity. The most sensitive and specific tool for diagnosis of early HCV
      viraemia was the detection of HCV core Ag by ELISA when compared to molecular
      biological methods.

PMID- 15724393
TI  - Local expression of IL-4 and IL-5 in perennial allergic rhinitis and their
      modulation by topical corticosteroid therapy.
AB  - Perennial allergic rhinitis (PAR) is an increasing problem for which new and
      exciting therapies are being developed. A T(H)2-polarized cytokine pattern is
      thought to predominate regulating local IgE synthesis and cell recruitment in PAR
      and the development of intranasal steroids has resulted in several agents with
      quick actions, localized effects and great efficacy in its management. The aim of
      work was to determine the differences in the local expression of IL-4 and IL-5 in
      patients with PAR compared to non-atopic healthy controls and investigate the
      relationship between the expression of these cytokines and the clinical aspects
      of the disease. Also to evaluate local expression of these cytokines in some of
      these patients before and after treatment with intranasal steroids (fluticasone
      proprionate). Nasal biopsies from 37 patients with PAR before therapy and from 8
      of them after receiving corticosteroids as local nasal spray were taken. PAR was
      confirmed by a history of perennial nasal blockage, discharge, and/or sneeze for
      at least 2 years before the study and by positive skin prick test. Also nasal
      biopsies were taken from 20 age and gender matched non-atopic controls. Biopsies
      were analyzed using a reverse transcription-polymerase chain reaction (RT-PCR) to
      investigate local expression of IL-4 mRNA. Enzyme immunoassay was used for
      estimation of IL-5 levels in the nasal mucosa. By using the ROC curve; (11 pg/ml)
      was estimated as a cut-off value for IL-5 where levels below this cut off were
      considered negative. This study showed that the most common causative allergens
      in PAR were mite dust, followed by wool & pigeon then mixed moulds. There was a
      significant relation between expression of IL-4 and IL-5 and the occurrence of
      allergic rhinitis where mRNA of IL-4 was detected in 17/37 [46%] of patient group
      and in 3/20 (15%) of the control group (P < 0.05). IL-5 levels were more than the
      calculated cut off value in 22/37 (59.5%) of patient group as compared to 4/20
      (20%) in the control group (P < 0.01). Also a high significant association was
      found between IL-4 & IL-5 (P < 0.01) in patient group. However, no significant
      relation was found between signs & symptoms of AR or patients' age or gender and
      cytokines expression. Corticosteroid nasal spray treatment showed a significant
      reduction in IL-4 gene expression and IL-5 positivity (P < 0.05). It is concluded
      that IL-4 & IL-5 have an important role in the pathogenesis of PAR and
      corticosteroid nasal spray is effective in exerting an immunomodulatory activity
      by reducing IL-4 & IL-5 expression.

PMID- 15724395
TI  - [Phytochemical and pharmacological research progress in Leontopodium medicinal
      plants].
AB  - This paper reviewed the phytochemical and pharmacological research progress in
      Leontopodium medicinal plants, including the resource distribution, the chemical
      constitutes, the pharmacological activities and clinical application. The review
      has provided some information for the study and development of Leontopodium
      medicinal plants in future.

PMID- 15724396
TI  - [General situation of the study on the toxicity of Cinnabaris].
AB  - Traditional Chinese medicine (TCM) experienced a gradual course in recognition of
      the toxicity of Cinnabaris from "nontoxic" to "toxic". The ancient doctors of TCM
      understood both the toxic property and the regularity of increasing toxicity of
      Cinnabaris. In long-term clinical practice they developed the methods of
      detoxification guiding the safe use of Cinnabaris. The toxicity of Cinnabaris is
      produced by mercury existed in it. Improper administration leading to an acute
      absorption or chronic accumulation was the main cause of clinical adverse
      effects. Kidney was the main poisoning target organ. On the other hand,
      improperly combinative application of Cinnabaris with other drugs of TCM or
      western medicine could increase the toxicity. Therefore, the crucial approach to
      avoid the poisoning is to use Cinnabaris properly.

PMID- 15724397
TI  - [Effects of four species of endophytic fungi on the growth and polysaccharide and
      alkaloid contents of Dendrobium nobile].
AB  - OBJECTIVE: To study the effects of four species of endophytic fungi on the growth
      and polysaccharide and alkaloid contents of cultured Dendrobium nobile. METHOD:
      Each fungal strain was cultured together with D. nobile, and the plant weight as
      well as the polysaccharide and alkaloid contents were measured. RESULT: Compared
      with the control group, Mycena sp. (MF23) was found to decrease the fresh weight
      of D. nobile by 24.9% (P < 0.01). All four species of fungi have no effect on the
      dry weight of this plant. On the other hand, Epulorhiza sp. (MF18) and MF23 could
      increase the percent of dry weight of seedlings (P < 0.05). Epulorhiza sp. (MF15)
      and MF24 increased the number of aerial roots by 4.25 times and 4.14 times
      respectively (P < 0.01). MF23 decreased the numbers of basal roots by 46.5% (P <
      0.01). MF15, MF18, MF23 and MF24 were shown to increase the content of
      polysacchride by 153.4%, 52.1%, 18.5% and 76.7%, respectively. MF23 also
      increased the content of total alkaloid by 18.3%. CONCLUSION: Endophytic fungi
      cultured together with D. nobile could affect the growth of this plant; they also
      increase total alkaloid and polysaccharide contents.

PMID- 15724398
TI  - [A study on quality standard for Herba Siegesbeckidae].
AB  - OBJECTIVE: To establish the qualitative and quantitative methods of Herba
      Siegesbeckiae. METHOD: A TLC method was used for qualitative identification and a
      HPLC analysis was applied for quantitative determination of Herba Siegesbeckiae
      with kirenol as the reference substances. RESULT: Chloroform-methanol-formic acid
      (25:5:1) as a mobile phase of TLC, the spot of kirenol can be easily detected;
      Methanol extracts of Herba Siegebeckiae were separated on a Polaris C18 column
      with acetonitrile-water (25:75) as mobile phase and kirenol was separated well.
      The average content of kirenol in Herba Siegebeckiae was 0.14%. A good linear
      relationship between the peak areas and injected amounts of kirenol in the range
      of 0.19-14.9 microg and the average recovery was 100.0% (RSD = 2.4%). CONCLUSION:
      The method can be used for qualitative identification and quantitation
      determination of Herba Siegesbeckiae.

PMID- 15724399
TI  - [Study of diffusion of muscone in different inclusion complexes and liposome
      through mouse (correction of rat) skin in vitro].
AB  - OBJECTIVE: To compare the penetrating rate of muscone in different inclusion
      complexes and liposome. METHOD: The transdermal effect of muscone in different
      inclusion complexes and liposome was studied comparatively on mouse [corrected]
      skin with 40% EtOH as the absorption solution and with an improved Franz diffuse
      cell. RESULT: Among the different inclusion complexes and liposome, the
      penetrating rate of muscone in the HP-beta-cyclodextrin inclusion and the
      liposome were higher than muscone, and that of muscone in the beta-cyclodextrin
      inclusion is the lowest. CONCLUSION: The HP-beta-cyclodextrin inclusion and the
      liposome can hence the muscone transdermal speed.

PMID- 15724400
TI  - [Studies on dissolution rate in vitro of silymarin dropping pill].
AB  - OBJECTIVE: To test the dissolution rate of silymarin dropping pill as well as to
      be compared with other three commercial products of the silymarin. METHOD: By UV
      spectrophotometry, we studied the dissolution conditions of silymarin dropping
      pill and compared its dissolution rate with Yiganling tablets (film-coating,
      sugar-coating) and Legalon capsule which are available in the market. RESULT: The
      dissolution parameters T50 and Td of silymarin dropping pill, Yiganling tablet
      (film-coating), Yiganling tablet (sugar-coating) and Legalon capsule are 6.78,
      9.85 min, 51.01, 73.78 min, 74.35, 86.97 min and 53.10, 72.65 min. CONCLUSION:
      The dissolution rate of silymarin dropping pill is superior to that of two kinds
      of Yiganling tablets and Legalon capsule.

PMID- 15724402
TI  - [Studies on the chemical constitutents in herb of Verbena officinalis].
AB  - OBJECTIVE: To isolate and identify the chemical constituents from Verbena
      officinalis. METHOD: The compounds were isolated by means of chromatography and
      the structures were determined on the basis of physical and spectral analysis.
      RESULT: Four compounds were isolated and identified as apigenin (I), 4'
      hydroxywogonin (II), verbenalin (III) and hastatoside (IV). CONCLUSION: Compounds
      I and II were obtained from the genus for the first time.

PMID- 15724401
TI  - [Determination of triptolide in Tripterygium total terpenoids tablets by HPLC].
AB  - OBJECTIVE: To develop a HPLC method for determination of triptolide in
      tripterygium total terpenoids tablets. METHOD: A Lichrospher CN column was used
      with ethanol and water for gradient elution. The detection wavelength was set at
      255 nm. RESULT: The linear relationship of the concentrations and peak areas was
      good in range of 0.742-59.4 microg x mL(-1) (r = 0.9998). The average recovery
      was 99.2%, RSD% = 1.7%. CONCLUSION: The method is simple, rapid and accurate and
      can be used for quality control of the tablets.

PMID- 15724403
TI  - [Studies on chemical constituents in bark of Larix olgensis var. koreana].
AB  - OBJECTIVE: To study the chemical constituents in bark of Larix olgensis var.
      koreana. METHOD: The compounds were isolated with silica gel column
      chromatography and their structures were elucidated on the basis of spectral
      analysis (IR, EI-MS, 1H-NMR, 13C-NMR). RESULT: Eight compounds were isolated and
      identified as isopimaric acid (I), beta-sitosterol (II), 24R,5alpha-stigmast-3,6
      dione (III), larixol (IV), ferulic acid (V), lariciresinol (VI),
      secroisolariciresinol (VII) and isolariciresinol (VIII). CONCLUSION: All the
      compounds were isolated from this plant for the first time.

PMID- 15724404
TI  - [Studies on chemical constituents in herb of Lamium maculatum var. kansuense
      (II)].
AB  - OBJECTIVE: To study the chemical constituents from Lamium maculatum var.
      kansuense. METHOD: The chemical constituents were isolated and repeatedly
      purified on silica gel column and the structures were elucidated by the NMR
      spectra and physico-chemical properties. RESULT: Six compounds were obtained and
      identified as polypodine B (I), 5-OH-8-epiloganin (II), shlanzhiside methyl ester
      (III), liriodendrin (IV), quercitroside (V), uridine (VI). CONCLUSION: Compound
      IV was found from genus Lamium for the first time and the rest of the compounds
      were found from Lamium maculatum var kansuense for the first time.

PMID- 15724405
TI  - [Determination of sophoramine by spectrofluorimetry].
AB  - OBJECTIVE: The fluorescence property of sophoramine was studied and a
      spectrofluorimetric method was established to determine the sophoramine content.
      METHOD: In 20% ethanol solution, with excitation wavelength at 394 nm and
      emission wavelength at 467 nm, the fluorescence intensity of sophoramine can be
      detected by the fluorophotometer. RESULT: Sophoramine content can be determined
      with external standard method by fluorophotometer. The linear relationship
      between fluorescence intensity and concentration is kept in the range of 10-200
      microg x mL(-1). The regression equation is Int = 1.137C + 3.875. The recovery
      rate is 98%-102%. CONCLUSION: Utilizing the fluorescence character of
      sophoramine, its content can be determined fast and sensitively. The analysis is
      not interfered by the existing matrine and oxymatrine. The method has high
      selectivity and the results is satisfying.

PMID- 15724406
TI  - [Effect of Rhizoma pinelliae on vomiting in minks].
AB  - OBJECTIVE: To study emetic and anti-emetic effects of Rhizoma pinelliae in minks.
      METHOD: The emetic effect of raw pinellia 2 g kg(-1) (i.g.) was investigated.
      Three preparations of Rhizoma pinelliae (processed with ginger) were made by
      ethanol extraction, water extraction and water decoction respectively and their
      effects on emesis model induced by cisplatin (7.5 mg kg(-1), i.p.) or apomorphine
      (1.6 mg kg(-1), s.c.) were then studied; the effect of the decoction of ginger
      processed Rhizoma pinelliae on rotation-induced emesis model in minks was also
      observed. RESULT: The emesis was induced by raw pinellia in minks (P < 0.01);
      ginger-processed Rhizoma pinelliae, metoclopramide and ondansetron significantly
      inhibit the emesis induced by cisplatin and apomorphine (P < 0.05). CONCLUSION:
      Ginger-processed Rhizoma pinelliae exhibits a anti-emetic effect in minks, which
      may be mediated by inhibiting the function of the vomiting center in central
      nervous system.

PMID- 15724408
TI  - [Protective effect of Armillaria mellea polysaccharide on mice bone marrow cell
      damage caused by cyclophosphamide].
AB  - OBJECTIVE: To observe the effect of Armillaria mellea polysaccharide on mice bone
      marrow cells damage caused by Cyclophosphamide. METHOD: Kunming purebred mice
      were used and stochastic divided into 5 groups: normal control group, positive
      control group (rhG-CSF 20 microg x kg(-1) x d(-1)), damage group of
      Cyclophosphamide (150 mg x kg(-1) x d(-1)), the protective group with A. mellea
      polysaccharide, low dose (25.0 mg x kg(-1) x d(-1)) and high dose (50.0 mg x kg(
      1) x d(-1)). Positive control was s.c. rhGCSF 6 d and i.p. Cyclophosphamide 3 d.
      A. mellea polysaccharide was i.p. 8 d. and Cyclophosphamide i.p. 3 d. WBC, RBC,
      PLT, BMNC were counted in peripheral blood and bone marrow cells. The myelogram
      were analyzed in bone marrow. RESULT: The WBC, RBC, PLT, BMNC of protective group
      and positive control group were higher than damage group (P < 0.01) significantly
      high dose group increaser than low dose group in protective group the numbed of
      Promyelocytic and lobulation nuclear of marrow. CONCLUSION: A. mellea
      polysaccharide has preferably protective effect on damaging mice bone marrow cell
      caused by Cyclophosphamide.

PMID- 15724407
TI  - [The study of tetrandrine on reversion of P170 and apoptosis of obtained multi
      drug resistance of mice S180's tumour cell].
AB  - OBJECTIVE: To observe the effect of tetrandrine on reversion of mice S180's
      obtained multi-drug resistance tumor cell induced by chemotherapy by PFC. And
      then discuss the molecular mechanism of it for the use of TCM in clinic to
      restrain the drug-resistant of chemotherapy, thereby improve the curative effect.
      METHOD: By the methods of less dosage of chemotherapy PFC, give the mouse
      cisplatin 3 mg x kg(-1) i.p., once a week; CTX and 5-FU 3 mg x kg(-1) i.g. four
      weeks, set up the mice models of multi-drug resistance of S180 tumor cell, and
      then observe the P170, Fas, CD54 and apoposis by flow cytometry. RESULT:
      Tetrandrine can obviously lower the express of P170 increase the express of Fas
      and the apoposis of drug resistant tumor cell. And at the same time it can
      obviously reduce the express of intercellular adhesion molecule (CD54).
      CONCLUSION: Terandrine, with its adjustment of correlated biotic active matter,
      can intervene the occurrence of the multi-drug resistance of tumor cells induced
      by chemotherapy.

PMID- 15724409
TI  - [Effects of berberine on adiponectin mRNA expression in 3T3-L1 adipocyte].
AB  - OBJECTIVE: To explore the effects of berberine and insulin on adiponectin mRNA
      expression in 3T3-L1 adipocyte. METHOD: The 3T3-L1 adipocyte was treated with
      berberine and insulin for 48 hours, the level of adiponectin mRNA in 3T3-L1
      adipocyte expression was determined with semiquantity RT-PCR using beta-actin as
      internal reference. RESULT: The level of adiponetin mRNA in 3T3-L1 adipocyte was
      increased after treated with berberine only (P < 0.05), the effect of berberine
      was inhibited by high concentration insulin (P < 0.05). CONCLUSION: In vitro,
      berberine increases the expression of adiponectin in 3T3-L1 adipocyte, insulin
      inhibits the effect of berberine.

PMID- 15724410
TI  - [Effects of Epimedium pubescens icariine on proliferation and differentiation of
      human osteoblasts].
AB  - OBJECTIVE: To study the effects of epimedium pubescens icariine on the
      proliferation and differentiation of human osteoblasts. METHOD: Human osteoblasts
      were obtained by inducting human marrow mesenchymal stem cells (hMSCs)
      directionally. MTT was used to observe the proliferation and activity of ALP was
      assayed to observe the differentiation of the third passage human osteoblasts
      cultured in vitro. The expression of BMP-2 mRNA was checked by RT-PCR. RESULT:
      Epimedium pubescens icariine at the dose of 20 microg x mL(-1) increased greatly
      the proliferation and differentiation of human osteoblasts and promoted the
      expression of BMP-2 mRNA. CONCLUSION: Epimedium pubescens icariine enhances
      significantly the proliferation and differentiation of human osteoblasts, which
      may be mediated by increasing the expression of BMP-2 mRNA.

PMID- 15724411
TI  - [Histopathological study on allergic rhinitis treated with Centipeda minima].
AB  - OBJECTIVE: The aim of this study was to investigate the mechanisms of C. minima
      in the treatment of allergic rhinitis. METHOD: An allergic rhinitis animal model
      induced by ragweed pollen was established. After treatment with an active extract
      of C. minima, histopathological changes in the nasal mucosa of guinea pig were
      observed by transmission electron microscope. RESULT: In the allergeic rhinitis
      model group, there appear a large number of lysosomes in the nasal epithelium
      with organelles vacuolated and nucleus deformed. Cells in the proper lamina of
      connective tissue were disarranged with organelles damaged, and there was also
      infiltration of eosinophils and mast cells in the connective tissue. However, in
      the treatment group receiving C. minima extract, the pathological changes
      mentioned above were significantly decreased. CONCLUSION: C. minima is effective
      in treating allergic rhinitis.

PMID- 15724412
TI  - [Different mechanisms mediated the potentiation uterine smooth muscle caused by
      Polygala tenuifolia decoction progesterone in virginal rats].
AB  - OBJECTIVE: To research the effects of Polygala tenuifolia decoction on
      myoelectric activity of uterine smooth muscle and contractile activity of uterine
      smooth muscle strips of virginal rats. METHOD: To record the effects of P.
      tenuifolia decoction on myoelectric activity of uterine smooth muscle and
      contractile activity of uterine smooth muscle strips of virginal rats with biolap
      410 biological system. Five blocking agents were used to study their mechanisms
      respectively. RESULT: Different dosages of water extract of P. tenuifolia (0.02,
      0.04, 0.08 g x kg(-1)), could significantly potentiate uterine myoelectric
      activity and contractile activity of virginal rats. CONCLUSION: The effect of P.
      tenuifolia on myoelectric activity of uterine smooth muscle and contractile
      activity of uterine smooth muscle strips in rats may be mainly associated with H1
      receptor, L-voltage-dependant calcium channels or prostaglandin synthese, its
      nothing to M receptor.

PMID- 15724413
TI  - [Cardiac surgery without transfusion in 2005].
AB  - PURPOSE: Between January 1991 and October 2003, 200 Jehovah Witnesses adult
      patients underwent elective cardiac surgery. To asses the impact on continuing
      progress of blood saving protocols and the increasing operative risk of patients
      proposed to surgery, we have re-assessed our results in this specific population.
      METHODOLOGY: Files of the first 100 patients operated upon between 1991 and 1998
      were reviewed, and compared to the following 100 ones treated between 1998 to
      today. All patients were scored using the Euroscore model. RESULTS: In the latest
      series, patients are older (68 vs 51) and 13% underwent an iterative procedure,
      although there was none in the first series. Three deaths occurred after one
      month at the beginning of our experience, only one in the latest series.
      Operative risk factors had distinctly deteriorated, with more redux, and ejection
      fraction lower than 35%. Major progress to maintain morbi-mortality stability
      were multifactorial: preoperative erythropoietin in order to reach an haemoglobin
      minimal value of 14 g/dL, Cornell University protocol, mini-ECC, warm blood
      cardioplegia, ultra-early extubation. CONCLUSION: Cardiac surgery without
      transfusion can be realised with an equivalent risk to that of classical surgery,
      despite an operative risk aggravation, due to the association of recent
      conservative techniques.

PMID- 15724414
TI  - [Evolution of the Fontan operation and results in patients with single ventricles
      or mixed congenital malformations].
AB  - STUDY OBJECTIVES: To examine the results of right heart derivations and clinical
      outcomes according to preoperative characteristics and operative strategy
      implemented. METHODS: Fontan operations were performed in 65 patients (mean age =
      10.3 years, 41 males). The majority of cardiopathies were single ventricles (SV)
      with (49% of patients) or without (26%) tricuspid atresia. A palliative
      bidirectional cavo-pulmonary (BCP) anastomosis was performed prior to Fontan in
      15 patients. Intra-atrial Fontan tunnelling was performed in 43 patients,
      Kreutzer-type operations in 10, and extracardiac tubes were used in 8 patients.
      The mean duration of follow-up was 6.1 +/- 0.3 years. RESULT: The 30-day
      mortality was 13.8%. Early mortality was higher among patients with SV with than
      without tricuspid atresia (P < 0.01), and among patients < 4 years old. Early
      reoperations were required in 5 patients, including dismounting in 1, BCP
      anastomosis after Kreutzer procedure in 1, and tube thrombosis in 1 patient. A
      single death occurred past 30 days, and late adverse events included protein
      losing enteropathy in 1 patient, complete atrioventricular block in 1, and tube
      thrombosis treated with heparin in 2 patients. At the end of follow-up, 75% were
      in New York Heart Association functional class I. CONCLUSION: Our intermediate
      term results of Fontan-type operations were satisfactory, and steadily improving.
      The prognosis was better in patients operated at age 4 or older. A prior BCP
      anastomosis improved the results. A higher morbidity was observed with intra-
      than with extra-atrial Fontan procedures. The merit of fenestration procedures
      with respect to morbidity remains the be evaluated.

PMID- 15724415
TI  - [Pseudo-aneurysms of the ascending aorta in patients previously operated for
      acute aortic dissection].
AB  - Pseudo-aneurysms of the ascending aorta are a rare but serious complication of
      surgery for acute dissection of the aorta. The diagnostic methods and surgical
      technique have changed in recent years. The authors report their experience over
      a period of 20 years. From January 1981 to December 2001, 21 patients underwent
      reoperation for pseudo-aneurysms of the ascending aorta. The average age was 54.2
      +/- 3 years. Diagnosis is no longer based on aortography but on transthoracic or
      oesophageal multiplane echocardiography, thoracic spiral computed tomography or
      magnetic resonance imaging. Four patients presented with a recent history of
      severe pulmonary oedema. The risk associated with reopening the sternum is
      avoided by current operative techniques. The authors have chosen anterograde
      perfusion of the cervical arteries by direct canulation for cerebral protection.
      The operative mortality at one month is high (30%). All patients who had
      pulmonary oedema or cardiogenic shock in the immediate preoperative period died.
      There were no neurological complications. Twelve patients survived and one has to
      undergo a further operation for recurrence of the pseudo-aneurysm. The authors
      conclude that patients operated for dissection of the aorta must be followed up.
      It is important to resect as much as possible of the pathological aorta during
      the initial operation to avoid the risk of pseudo-aneurysm formation, at least in
      the proximal segment of the ascending aorta.

PMID- 15724416
TI  - [Feasibility and significance of a transoesophageal electrophysiological
      investigation in children and adolescents with Wolff-Parkinson-White syndrome].
AB  - An electrophysiological investigation is the most reliable means of detecting
      malignant forms of Wolff-Parkinson-White syndrome (WPW). However, an endocavity
      investigation is an invasive procedure, especially in young subjects with few
      symptoms. The aim of this study was to examine the feasibility and results of an
      electrophysiological study performed by the transoesophageal route in children
      with WPW. The study was performed in 70 children aged between 11 and 19 years
      (mean 15 +/- 3) with an obvious ECG appearance of WPW: 13 had dizziness or
      syncope (group I), 25 had tachycardia (group II) and 32 were asymptomatic (group
      III). The ages were similar in all three groups. The transoesophageal
      electrophysiological investigation without premedication consisted of atrial
      stimulation at increasing frequencies and programmed atrial stimulation using one
      and two extra stimuli delivered in the basal state and after infusion of 2 to 5
      microg of isoproterenol. RESULTS: The investigation was completed in all the
      children except one in group II. A paroxysmal junctional tachycardia was induced
      in 7 group I children (54%), 22 in group II (92%) and 4 in group III (12.5%).
      Atrial fibrillation lasting more than one minute was induced in 7 group I
      children (54%), 6 in group II (25%) and 6 in group III (19%). The percentage of
      malignant forms combining rapid conduction in the bundle of Kent at a rate of
      more than 240/min in the basal state or more than 300/min with isoproterenol, and
      atrial fibrillation was 54% in group I, 21% in group II, and 22% in group III. In
      conclusion, a transoesophageal electrophysiological investigation was possible as
      an outpatient procedure in children older than 10 years, and allowed the
      detection of potentially serious forms whatever the indication for the
      investigation, with nevertheless a significantly higher incidence in those
      presenting with dizziness or syncope. The incidence of 22% for potentially
      malignant forms in asymptomatic children provides an incentive to recommend an
      ECG in all children older than 10 years participating in an active sport in order
      to detect WPW and to propose oesophageal investigation.

PMID- 15724417
TI  - [Doppler echocardiographic study of left ventricular diastolic function in
      hemodialysis patients].
AB  - OBJECTIVES: The purpose of this study is to examine the diastolic dysfunction
      particularities in hemodialysis patients and to identify the parameters having
      the most discriminating power of diastolic dysfunction. METHODS: Conventional
      Doppler echocardiography study implies left ventricular diastolic function from
      Doppler transmitral flow (E/A), color M-mode flow propagation velocity (Vp) and
      combined indexes: ratio of peak E-wave velocity to Vp (ENp) and difference in
      duration of pulmonary venous and mitral flow at atrial contraction (Ap-Am).
      RESULTS: Left ventricular diastolic dysfunction is found in 86% of the 100
      hemodialysis patients: abnormal relaxation pattern 52%, pseudo-normal pattern
      21%, restrictive pattern 13%. Left ventricular hypertrophy is independent of
      blood pressure (eta2=3.386; p>0.06). Diastolic function pattern has no relation
      with duration of dialysis treatment (F=2.637, p>0.05) or left ventricular mass
      (F=4.298, p>0.06). We noted correlations with age for all parameters of
      transmitral Doppler flow (p<0.01), Vp and systolic fraction except combined
      indexes (p>0.05). Doppler parameters of which discriminating power is significant
      (p<0.001) are in deceasing order: isovolumic relaxation time, E/A, Vp, early
      filling deceleration time, Ap-Am, E/VP and systolic fraction. The parameter Vp
      discriminates normal filling from abnormal or pseudo-normal patterns. However it
      doesn't allow any discrimination between abnormal and pseudo-normal patterns or
      abnormal and restrictive patterns. Discriminating analysis classify correctly
      100% of pseudo normal pattern patients with 2 variables (isovolumic relaxation
      time and Vp or VP with E/Vp). Factor analysis suggests that Vp characterizes
      normal pattern and E/A ratio and Ap-Am characterize restrictive pattern.
      CONCLUSION: Parameters of diastolic function discriminating value is different
      from one stage to another. VP characterizes normal pattern, combined indexes
      restrictive pattern. Vp and isovolumic relaxation time discriminates normal from
      pseudo-normal pattern.

PMID- 15724418
TI  - [Obesity and cardiac failure].
AB  - Obesity alone is the cause of 11% of cases of cardiac failure in men and 14% of
      cases in women in the United States. The frequency of obesity continues to rise
      in our country, 41% of our compatriots being obese or overweight. It is expected
      that obesity will become an important cause of cardiac failure in the coming
      years. The Framingham study showed that, after correction for other risk factors,
      for every point increase in body mass index, the increase in risk of developing
      cardiac failure was 5% in men and 7% in women. There are three physiopathological
      mechanisms to explain the adverse effects of obesity on left ventricular
      function: an increase in ventricular preload secondary to increased plasma volume
      induced by the high fatty mass; an increase in left ventricular afterload due to
      the common association of hypertension generated by activation of the sympathetic
      nervous system by hyperinsulinism; and systolic and diastolic dysfunction due to
      changes in the myocardial genome and coronary artery disease induced by risk
      factors of atherosclerosis aggravated by obesity. The adipocyte also secretes a
      number of hormones which act directly or indirectly on the myocardium:
      angiotensin II, leptin, resistin, adrenomedulin, cytokines. These haemodynamic
      and hormonal changes profoundly modify the genetic expression of the myocardium
      in obesity, favourising hypertrophy of the myocyte and the development of
      interstitial fibrosis. Whether it be eccentric in the absence of hypertension or
      concentric when hypertension is associated with obesity, left ventricular
      hypertrophy, although normalising left ventricular wall stress, has adverse
      consequences causing abnormal relaxation and decreased left ventricular
      compliance. Therefore, in obese patients, two forms of cardiac failure may be
      observed. The more common is due to diastolic dysfunction, obesity being one of
      the principal causes of cardiac failure with preserved systolic function. Cardiac
      failure due to systolic dysfunction is less common and may be observed in cases
      with inappropriate left ventricular hypertrophy which does not normalise abnormal
      left ventricular wall stress leading to cardiomyopathy, and in cases with
      associated coronary artery disease. Whatever the underlying mechanism, the
      diagnosis of cardiac failure is made more difficult by obesity. From the
      prognostic point of view, in the global population of patients with cardiac
      failure, obesity improves survival because it counteracts the adverse effect of
      cachexia; however, obesity increases the risk of sudden death. In fact, obesity
      is associated with dynamic change in QT interval. In cases of cardiac failure
      secondary to obesity-related cardiomyopathy, loss of weight leads to an improved
      functional status and a reduction of left ventricular remodelling and an increase
      of the ejection fraction.

PMID- 15724419
TI  - [The heart and aerobatics].
AB  - Aerobatics is an aerial sport which has many physiological constraints,
      principally cardiovascular, with a risk if not adapted of sudden mid-air
      incapacity which could jeopardise aviation safety, and thus justifies the
      selection and surveillance of pilots. The aeronautical constraints during flight
      are multiple, related to the environment traversed, how the aircraft functions
      and its movements. Those which cause accelerations (+G in particular) pose the
      problem of haemodynamic tolerance because they can induce loss of consciousness
      due to cerebral hypoxia. Tolerance of acceleration varies among individuals; it
      can be improved with training, certain protective manoeuvres, and is reduced by
      hypoxia, certain medications, dehydration and heat. Moreover, in aerobatics
      certain tricks require manoeuvres which reduce this tolerance to +G
      accelerations. This is the "push-pull" effect (_G acceleration immediately
      followed by +G acceleration). This leads to a risk of sudden loss of
      consciousness with a load factor much lower than that which the pilot knows he is
      capable of tolerating. Besides the haemodynamic effects, the existence of an
      actual acceleration cardiomyopathy has been suggested but has not been proven in
      man. Finally, while changes in cardiac rhythm during accelerations are usual and
      relate to changes in vaso-sympathetic balance, ventricular and supra-ventricular
      rhythm disturbances are rare and are related to the intensity and duration of the
      acceleration.

PMID- 15724420
TI  - [Atrial remodeling, systemic hypertension, stroke].
AB  - Atrial remodeling has been demonstrated to be associated with rapid atrial pacing
      or with hemodynamic overload. It may refer to changes in electrophysiological
      properties and/or in structure and function. Hemodynamic overload of the atria
      has been found to be an important pathogenic factor of atrial fibrosis, providing
      a morphological substrate for atrial fibrillation. This finding could partly
      account for the high risk of stroke in hypertensive patients. In this respect, a
      strong involvement of the renin angiotensin system has been suggested by
      experimental, clinical and epidemiological data. Thus, prevention or even partial
      regression of atrial remodeling could be reasonably expected from ACE-inhibitors
      and angiotensin 2-blockers.

PMID- 15724421
TI  - [Biochemical evaluation of the results of lipid regulating treatment in France].
AB  - The objective of the SPOT study (Study of Practice versus Objectives of
      Treatment) was the biochemical evaluation of the results of long term lipid
      regulating treatment in France, compared to the objectives defined by AFSSAPS
      (French regulatory agency for the safety of medical products) in 2000. A random
      sample of doctors was recruited in 21 French regions by the Regional Health
      Observation service. To be included in the SPOT study, the patients had to be on
      lipid regulating medication for at least six months and consent to biochemical
      evaluation following a consultation. A sample of 641 doctors examined 2,479
      patients treated for 7 years on average. These middle aged patients (aged 63 +/-
      11 years) were mostly taking statins (72%). They had an average total cholesterol
      level of 5.41 +/- 1.01 mmol/L (2.10 +/- 0.39 g/L). and LDL of 3.25 +/- 0.93
      mmol/L (1.26 +/- 0.36 g/L), reflecting previous results and confirming the
      stability of their treatment. In primary prevention and in low risk subjects
      (with less than 2 associated risk factors), the AFSSAPS objectives were achieved
      in 95% of cases. In secondary prevention or in very high risk subjects (at least
      3 associated risk factors 0), 35% of patients had LDL cholesterol greater than
      3.4 mmol/L (1.30 g/L). The SPOT study, performed on subjects who had in theory
      been stabilised with lipid regulating medication, gave two conclusions:
      cardiovascular prevention with lipid regulating medication is improving in
      France, and the subjects at greatest risk attain the recommended objectives less
      often despite the expected benefit of treatment being higher.

PMID- 15724422
TI  - [Stress echography and pacemakers].
AB  - The non-invasive investigation of myocardial ischaemia in pacemaker patients is a
      common problem. Stress echocardiography seems interesting for this indication,
      but very few data are available for patients fitted with a pacemaker. We wanted
      to know whether it would be useful to propose a conventional stress echography,
      under dobutamine/atropine, for these patients. One hundred stress echographies
      were performed at our centre between 1998 and 2004 in 113 consecutive ventricular
      paced patients at rest. We determined the degree of contraction asynchrony
      related to ventricular pacing and its impact on the interpretation of the test.
      In this series, the test proved contributory in 87% of cases, with disturbance of
      the target heart rate in 71% of cases, and contraction asynchrony hindering
      interpretation in only 11% of cases. Under the effect of the dobutamine/atropine
      combination, we observed passage into spontaneous rhythm in 54% of cases, with
      complete disappearance of septal asynchrony, thus facilitating interpretation of
      the test. It would therefore appear that conventional stress echography is the
      method of choice for the non-invasive investigation of myocardial ischaemia in
      patients fitted with a pacemaker, being well tolerated and contributory most of
      the time.

PMID- 15724423
TI  - [Apical left ventricular aneurysm without atrio-ventricular block due to a lamin
      A/C gene mutation].
AB  - Mutations in LMNA gene encoding two ubiquitously expressed nuclear proteins,
      lamins A and C, give rise to up to 7 different pathologies affecting specific
      tissues. Three of these disorders affect cardiac and/or skeletal muscles with
      atrio-ventricular conduction disturbances, dilated cardiomyopathy and sudden
      cardiac death as common features. RESULTS: A new LMNA mutation (1621C>T, R541C)
      was found in two members of a French family with a history of ventricular rhythm
      disturbances and an uncommon form of systolic left ventricle dysfunction. The two
      patients: the proband and his daughter, were affected and exhibited an atypical
      form of dilated cardiomyopathy with an unexplained left ventricle aneurysm
      revealed by ventricular rhythm disturbances without atrio-ventricular block.
      CONCLUSION: This finding reinforces the highly variable phenotypic expression of
      LMNA mutation and emphasizes the fact that LMNA mutations can be associated with
      different cardiac phenotypes.

PMID- 15724424
TI  - [Acute cardiomyopathy and severe hypocalcaemia].
AB  - Severe electrolyte imbalance is rarely the cause of cardiac decompensation. We
      report the case of a young patient with acute left ventricular failure due to
      severe hypocalcaemia secondary to the intestinal malabsorption of calcium with
      inflammatory bowel disease. The interesting feature of this case was the rapid
      haemodynamic deterioration and the total reversal within one week following
      correction of the hypocalcaemia.

PMID- 15724425
TI  - [Cardiac multifocal hydatid cyst].
AB  - Hydatid cysts in the heart are rare, with an unpredictable outcome and numerous
      complications, requiring rapid surgical management. We report the case of a 19
      year old female patient, who underwent surgery with extra corporeal circulation
      for a hydatid cyst of the interventricular septum of the heart, complicated by
      secondary pulmonary echinococcus infection, confirmed on CT and MRI. Resection of
      the cyst was performed via a right auriculotomy. The post operative period was
      favourable; the other pulmonary sites were treated medically. We emphasise the
      methods of diagnosis and management.

PMID- 15724426
TI  - A change of heart. FDR's death shows how much we've learned about the heart.

PMID- 15724428
TI  - Classroom to clinic.

PMID- 15724427
TI  - Shopper's special on flu shots.

PMID- 15724429
TI  - The cancer conundrum.

PMID- 15724430
TI  - What Larry meant to say.

PMID- 15724431
TI  - Enhanced insulin secretion from engineered 3T3-L1 preadipocytes by induction of
      cellular differentiation.
AB  - We have established insulin-secreting cell line, L1-INS/fur cells, by engineering
      3T3-L1 murine preadipocytes with human preproinsulin cDNA. Analysis with HPLC,
      mass spectrometry and immunological assay identified human insulin in the culture
      medium. Notably, secretion of insulin from L1-INS/fur cell was increased 8.2
      times higher after induction of cellular differentiation. The increment of
      insulin secretion during differentiation was further enhanced by additive
      treatment with thiazolidinedione, a promoting agent of adipocyte differentiation.
      This observation strongly suggests that the enhancement of insulin secretion is
      tightly associated with cellular differentiation process itself. Expression rate
      of the insulin transgene was not changed after the additional treatment with
      thiazolidinedione. On the other hand, furin gene expression by Northern analysis
      showed an increase, and Western analysis revealed even more reduction in cellular
      content of proinsulin. These results indicate that mechanism of the observed
      enhancement in insulin secretion during the differentiation is mainly due to
      increased capacity of the proinsulin processing by induction of furin. Results of
      our present study will provide important information on cell-based therapy using
      undifferentiated progenitors and tissue stem cells.

PMID- 15724432
TI  - Bovine hexokinase type I: full-length cDNA sequence and characterisation of the
      recombinant enzyme.
AB  - This study reports the revised and full-length cDNA sequence of bovine hexokinase
      type I obtained from bovine brain. Since dissimilarities have been observed
      between the published bovine hexokinase type I coding sequence (GenBank accession
      no. M65140) (Genomics 11: 1014-1024, 1991) and an analysed portion of bovine
      hexokinase type I gene, the entire open reading frame was re-sequenced and the
      ends of cDNA isolated by rapid amplification of cDNA ends. The coding sequences,
      when compared with the published bovine hexokinase type I, contained a large
      number of mismatches that lead to changes in the resulting amino acid sequence.
      The revisions result in a hexokinase type I cDNA of 3619 bp that encodes a
      protein of 917 amino acids highly homologous to human hexokinase type I. The
      expression of the recombinant full-length enzyme demonstrated that it was a
      catalytically active hexokinase. When characterised for its kinetic and
      regulatory properties, it displayed the same affinity for glucose and MgATP as
      the human hexokinase type I and was inhibited by glucose 6-phosphate
      competitively versus MgATP. The production of the N- and C-terminal recombinant
      halves of the enzyme followed by comparison with the full-length hexokinase
      indicated that the catalytic activity is located in the C-terminal domain.

PMID- 15724433
TI  - Evaluation of serum lipids and high-density lipoprotein subfractions (HDL2, HDL3)
      in postmenopausal patients with breast cancer.
AB  - Breast cancer patients are known to be at increased risk for developing other
      chronic diseases including cardiovascular disease. Studies by different
      investigators have shown a correlation between increased dietary fat or
      hypercholesterolemia and the occurrence of breast cancer. Since previous studies
      on lipoprotein subfractions in this type of cancer have been inconsistent, we
      evaluated the lipids and lipoprotein subfraction levels in postmenopausal
      patients with breast cancer in an attempt to identify the risk for the
      development of cardiovascular disease. The study included 132 patients, 56 of
      which were suffering from breast cancer, 32 from pancreatic and 44 age-matched
      controls. Total cholesterol (TC), triglycerides and lipoprotein fractions as well
      as TC/High density lipoprotein (HDL) and HDL2/HDL3 ratios were estimated by
      standard laboratory techniques. An increase in triglycerides and a decrease in
      HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients
      with breast cancer as compared to the controls (P < 0.05). The maximum changes in
      TC, and HDL concentrations were observed in patients with advanced disease.
      Analysis of indexes of atherosclerosis (TC/HDL, and HDL2/HDL3 ratios)
      demonstrated that breast cancer patients had significantly higher TC/HDL ratio
      (6.44+/-1.24) compared with controls (3.43+/-0.57, p = 0.001), and patients with
      pancreatic cancer (3.79+/-0.15, p = 0.027). The results have demonstrated an
      unfavourable lipid profile in untreated breast cancer patients with high
      atherosclerosis indexes. This observation is of great importance, considering the
      potential use of endocrine therapy that could result in further deterioration of
      lipid indexes. We propose the evaluation and monitoring of lipid profile prior
      and after the induction of hormonal therapy in breast cancer patients, as a
      routine in clinical setting.

PMID- 15724434
TI  - Effect of the preventive-therapeutic administration of melatonin on mammary
      tumour-bearing animals.
AB  - Melatonin has been reported to be involved in the feedback between neuroendocrine
      and immune functions and to exert oncostatic actions. Likewise, this hormone
      seems to lengthen life span in healthy animals. As of present, most studies have
      analysed the therapeutic effect of melatonin on cancer growth, but few have
      tested the preventive effect of melatonin in reducing the risk of cancer. Thus,
      the aim of this study was to evaluate the preventive-therapeutic effects of
      melatonin on rats with DMBA-induced mammary tumours, and to examine the effect of
      melatonin on the first line of cell defence against cancer (macrophages and NK
      cells) and on some of the neuroendocrine factors that are involved in the
      development of tumours (prolactin and catecholamines). Melatonin treatment (5
      mg/day/animal) began one month prior to DMBA (9,10-dimethyl-1,2-benzanthracene)
      administration to females Sprague Dawley rats. It was found that the treatment
      led to an increase in survival and in latency time in the tumour-bearing rats.
      Although the melatonin treatment did not influence either the phagocytic capacity
      of macrophages or the number of peripheral blood NK cells, it did stabilise the
      levels of prolactin by returning the concentrations of this hormone to those of
      the healthy animals. We conclude that melatonin can exert an oncostatic action,
      lengthening the survival time of mammary tumour-bearing animals, and suggest that
      this effect is due, at least in part, to regulating the neuroendocrine parameters
      of tumour-bearing animals, bringing them closer to their optimal physiological
      status.

PMID- 15724435
TI  - Serine dehydratase expression decreases in rat livers injured by chronic
      thioacetamide ingestion.
AB  - Serine dehydratase (SerDH) is a gluconeogenic enzyme involved in the catabolism
      of serine, which is regulated by the composition of their diet and their hormonal
      status in rats. This study examines how chronic injury caused to the liver of
      rats by the ingestion of thioacetamide (TAA) affects SerDH protein, mRNA levels,
      enzyme kinetics and its tissue location. After 97 days' oral intake of TAA, the
      activity of SerDH at all substrate concentrations assayed was about 60% lower
      than in controls. No significant differences in Km values were found between the
      treated group and controls. Immunoblotting and immunohistochemistry revealed a
      significant reduction in the level of SerDH protein in the livers of the treated
      rats. SerDH was detected specifically in the periportal zone of the hepatic
      acinus and this location did not change in response to TAA treatment. The level
      of SerDH mRNA, quantified by reverse transcription and polymerase chain reaction,
      was significantly lower in treated rats than in the controls. The present
      findings suggest that the SerDH expression is rendered to be down regulatory
      during chronic liver injury induced by TAA. These results enhance our
      understanding about the biochemical mechanisms implied in the control and
      integration of serine catabolism during liver injury in rat.

PMID- 15724436
TI  - Effect of GRP75/mthsp70/PBP74/mortalin overexpression on intracellular ATP level,
      mitochondrial membrane potential and ROS accumulation following glucose
      deprivation in PC12 cells.
AB  - Glucose regulated protein 75 (GRP75) is an important molecular chaperon belonged
      to the heat shock protein (HSP) family. To evaluate the effect of GRP75
      overexpression on PC12 cells under glucose deprivation, cell viability and
      mitochondrial function of GRP75-overexpressing PC12 cells and the vector
      transfected control PC12 cells were monitored during glucose deprivation. Upon
      exposure to glucose deprivation, GRP75-overexpressing PC12 cells exhibited more
      moderate cell damage than control PC12 cells. Both of the two groups of cells
      showed a decreased ATP level following an early increase in the condition of
      glucose deprivation, and the mitochondrial potential were also reduced in the
      similar manner in the two groups of cells. Control PC12 cells showed an immediate
      and rapid increase in ROS accumulation after the onset of GD treatment, and this
      accumulation was slowed and reduced in GRP75-overexpressing PC12 cells. These
      findings suggested that GRP75 could inhibit the ROS accumulation, and it may be
      associated with the cytoprotective effect of GRP75 overexpression upon glucose
      deprivation.

PMID- 15724437
TI  - Feeding apolipoprotein E-knockout mice with cholesterol and fat enriched diets
      may be a model of non-alcoholic steatohepatitis.
AB  - The present study was aimed (1) to investigate the effect of cholesterol and fat
      enriched diets on the development of steatohepatitis in apolipoprotein E-knockout
      mice, and (2) to study the chronological relationships between the development of
      hepatic alterations, hypercholesterolemia and atherosclerotic lesions in this
      experimental model. The study consisted of two protocols. Protocol 1 was used in
      90 mice subdivided in groups of 18. For 10 weeks, each group was given a diet
      with different fat and cholesterol contents. Protocol 2 was used in 42 mice,
      subdivided in four groups. Each group was given a diet enriched with cholesterol
      and palm oil and they were sacrificed at 8, 13, 18 and 24 weeks of age. Results
      were as following. (1) Mice given high fat/high cholesterol diets developed an
      impairment of liver histology consisting of fat accumulation, macrophage
      proliferation, and inflammation. (2) These effects were modulated by the type of
      fat: olive oil was mainly associated with macrovesicular steatosis and
      cholesterol plus palm oil with severe steatohepatitis. (3) There was a
      chronological and quantitative relationship between liver impairment and the
      formation of atheromatous lesions. We conclude that apolipoprotein E-knockout
      mice may be a useful model for investigating the mechanisms of diet-induced
      steatohepatitis.

PMID- 15724438
TI  - Cardiac syntrophin isoforms: species-dependent expression, association with
      dystrophin complex and subcellular localization.
AB  - Syntrophin is known to be a component of the dystrophin-glycoprotein complex
      (DGC), a membrane/cytoskeleton-anchoring structure that is essential for the
      maintenance of viability of sarcolemma. We purified DGC from hearts of human and
      several animal species, and compared their protein composition. While almost all
      components of DGC were present in various species, proteins with the apparent
      molecular mass of 50-65 kDa corresponding to syntrophin isoforms were very
      different among them. Three isoforms of syntrophin (alpha1, beta1, beta2) were
      expressed in hamster, rat and canine ventricles, whereas only alpha1-isoform was
      mainly expressed in human and rabbit ventricles. Immunohistochemical analysis
      revealed that alpha1-and beta2-syntrophins were co-localized in sarcolemma and in
      T-tubules of canine ventricles. However, despite membrane localization of most
      syntrophins, subcellular fractionation revealed that part of syntrophins were
      recovered in the cytosolic fraction devoid of other components of DGC, raising
      the possibility that syntrophins may play multiple roles in various intracellular
      sites of cardiac muscle cells. Species-dependent expression and unique
      subcellular localization of syntrophins in cardiac muscle may contribute to the
      variable severity of muscle dysgenesis caused by the same primary defect in
      components of DGC of human and other animal species.

PMID- 15724439
TI  - A Northwestern blotting approach for studying iron regulatory element-binding
      proteins.
AB  - At least two proteins binding to iron regulatory elements (IRE) in mRNA are
      known, designated as iron regulatory proteins (IRP) 1 and 2. Their binding
      activity is widely studied by electrophoretic mobility shift assays (EMSA), which
      resolves one or two bands depending on the species. We used Northwestern blotting
      to resolve this EMSA complex into four components, and identified two other IRE
      binding peptides present in HepG2 cell extracts. We designate these six peptide
      bands A to F on Northwestern blots, ranging in apparent molecular weight from 111
      to 37 kDa. Band C is lost when cells are preloaded with iron or when leupeptin
      (but not several other protease inhibitors) is included in the extraction buffer.
      Band E is also lost with leupeptin but increases with iron loading. Binding of
      all bands is sensitive to iron in vitro. Two-dimensional electrophoresis reveals
      additional processing, especially indicating charge variants of band C.
      Northwestern bands A and B both react with an antibody to IRP-1 on parallel
      Western blots. We conclude that cellular processing can produce multiple IRE
      binding species that may be involved in a more complex regulation of iron
      metabolism than generally appreciated. The Northwestern approach should
      facilitate studies of processing and binding requirements of proteins and
      peptides that recognize the IRE sequence.

PMID- 15724440
TI  - Thyroid hormones stimulate Na+-Pi transport activity in rat renal brush-border
      membranes: role of membrane lipid composition and fluidity.
AB  - Antecedent studies have suggested that lipid composition and fluidity of cellular
      membranes of various organs are altered in response to thyroid hormone status. To
      date, the effects of thyroid hormone status on these parameters have not been
      examined in rat renal apical membrane in regard to sodium-dependent phosphate
      transport. In the present study, we determined the potential role of alterations
      in cortical brush-border membrane lipid composition and fluidity in modulation of
      Na+-Pi transport activity in response to thyroid hormone status. Thyroid hormone
      status influences the fractional excretion of Pi, which is associated with
      alteration in renal brush-border membrane phosphate transport. The increment in
      Na+-Pi transport in renal BBMV isolated from Hyper-T rats is manifested as an
      increase in the maximal velocity (Vmax) of Na+-Pi transport. Further, the
      cholesterol content was significantly increased in renal BBM of Hypo-T rats and
      decreased in Hyper-T rats as compared to the Eu-T rats. The molar ratio of
      cholesterol/phospholipids was also higher in renal BBM from hypo-T rats.
      Subsequently, fluorescence anisotropy of diphenyl hexatriene (rDPH) and
      microviscosity were significantly decreased in the renal BBM of the Hyper-T rats
      and increased in the Hypo-T rats as compared to Eu-T rats. The result of this
      study, therefore, suggest that alteration in renal BBM cholesterol,
      cholesterol/phospholipid molar ratio, and membrane fluidity play an important
      role in the modulation of renal BBM Na+-Pi transport in response to thyroid
      hormone status of animals.

PMID- 15724441
TI  - Identification of conserved polar residues important for salt tolerance by the
      Na+/H+ exchanger of Schizosaccharomyces pombe.
AB  - The Na+/H+ exchanger is a ubiquitous protein that transports Na+ and H+ in
      opposite directions across cell membranes. In fission yeast, the Na+/H+ exchanger
      sod2 plays a major role in the removal of excess detrimental intracellular
      sodium. The effect of mutagenesis of conserved polar amino acids of sod2 was
      examined by expressing 10 different mutant forms of sod2 in sod2 deficient S.
      pombe and characterizing salt tolerance. Asp145, 266, 267, and Glu173 were
      critical for proper function of sod2. Asp241 had an intermediate effect on sod2
      function while mutation of Asp178 did not impair sod2 function. Simultaneous
      mutation of the Asp266, 267 pair impaired sod2 function. Mutation of each
      individual residue demonstrated that both were critical for sod2 function.
      Conservative mutations (Asp to Glu) of Asp266 and 267 failed to restore sod2
      function. The results suggest that acidic residues associated with transmembrane
      segments are important in function, possibly being important in binding and
      coordinating cations.

PMID- 15724442
TI  - Activation of MAPK kinase pathway by Gal/GalNAc adherence lectin of E.
      histolytica: gateway to host response.
AB  - Amoebiasis caused by the protozoan parasite Entamoeba histolytica is one of the
      leading parasitic causes of morbidity and mortality in the developing countries.
      Among the variety of virulence factors, an adherence lectin (Gal/GalNAc, 260 kDa)
      has been known to mediate colonization and subsequent host responses. It is a
      major cell surface antigen which is universally recognized by the immune sera of
      patients with amoebic liver abscess (ALA). The role of this lectin in cytolysis
      and phagocytosis of human colonic mucin glycoproteins has also been established.
      The objective of the present study was to elucidate the signal transduction
      events induced in response to Entamoeba histolytica derived Gal/GalNAc lectin in
      the target epithelial cells. We have attempted to define a pathway in target
      cells that could link this immunodominant antigen to a known biological pathway
      for target cell activation and triggering of subsequent disease
      pathology/parasite survival. Lectin stimulated cells showed immediate rise in
      (Ca2+)i concentration corresponding to 1517.31+/-16.3 nM (approximately) at 0-2
      min. The intracellular calcium also extruded from the cells as was measured by
      increase in calcium green-1 fluorescence. Expression of several protein kinases
      was checked by western blotting to delineate the signaling pathway. Results
      showed that the expression of PLA2, PI3K, Ras p21, Ras GAP, ERK-MAPK, p38MAPK and
      PKC was significantly increased. Expression of Raf-1 and MEK-1 was also found to
      be significant, as determined by intensity analysis. Overall, it indicated
      activation of MAPKinase pathway which is implicated in a variety of cellular
      functions. On the basis of our observations it can be stated that there is a
      calcium mediated activation of PKC in target cells, by lectin, which inturn
      activates cyclic nucleotides and other protein kinases. These protein kinases
      further phosphorylated downstream signals in a sequential manner, thus leading to
      the activation of MAPKinase cascade. Activation of MAPK cascade, in our studies,
      is implicated in a variety of physiological cellular functions including
      apoptosis, proliferation, cytoskeleton rearrangements and permeability changes.
      However, future screening of the genes responsible for the transcription and
      translation of new proteins and their biological functions in response to lectin
      stimulation will prove useful in understanding this host-parasite relationship.

PMID- 15724443
TI  - Akt signaling pathway in pacing-induced heart failure.
AB  - Marked changes in energy substrate utilization occur during the progression of
      congestive heart failure (CHF) where fatty acid utilization, as the primary
      source of cardiac energy, is severely diminished, oxidative phosphorylation is
      down-regulated, and glucose uptake and utilization increase. Neither the
      signaling events or the molecular basis for the shift in substrate utilization
      have yet been elucidated. This study was designed to examine in the canine model
      of paced-induced CHF, the potential role of the Akt pathway in signaling the
      metabolic transitions central to progression to heart failure. Myocardial Akt
      levels were elevated in early heart failure (after 1-2 weeks of pacing)
      accompanied by increased levels of oxidative stress, cytokine tumor necrosis
      factor-alpha (TNF-alpha) and free fatty acid accumulation, reduced activity
      levels of mitochondrial respiratory complexes III and V and apoptosis initiation.
      At severe heart failure (3-4 weeks of pacing), there was significant further
      increase in myocardial apoptosis, with pronounced decline in myocardial Akt
      kinase activity. At this later stage, there were no further changes in free fatty
      acid accumulation, complex V activity or in oxidative stress levels indicating
      that these changes primarily occurred in the earlier stage of evolving heart
      failure. In contrast, during severe heart failure, both the reduction in complex
      III activity and increase in TNF-alpha level became more pronounced. Our data
      provide critical support for the hypothesis that the Akt signaling pathway is a
      contributory element in the early signaling events leading to the progression of
      pacing-induced heart failure, accompanying the shift in substrate utilization.

PMID- 15724444
TI  - Combined treatment of sodium orthovanadate and Momordica charantia fruit extract
      prevents alterations in lipid profile and lipogenic enzymes in alloxan diabetic
      rats.
AB  - Momordica charantia Linn., commonly called bitter gourd, is a medicinal plant
      used in the Ayurvedic system of medicine for treating various diseases including
      diabetes mellitus. Sodium orthovanadate (SOV) is also well-known insulin mimetic
      and an antidiabetic compound. Our laboratory has been using reduced doses of SOV
      along with administration of herbal extracts to alloxan diabetic rats and has
      established this combination as a good antihyperglycemic agent. The present study
      was undertaken to investigate the effects of treatment of Momordica fruit extract
      (MFE) and sodium orthovanadate, separately and in combination, on serum and
      tissue lipid profile and on the activities of lipogenic enzymes in alloxan
      induced diabetic rats. The results show that there was a significant (p < 0.01)
      increase in serum total lipids, triglycerides and total cholesterol levels after
      21 days of alloxan diabetes. In the liver and kidney of diabetic rats the levels
      of total lipids and triglycerides also increased significantly (p < 0.01) while
      levels of total cholesterol decreased significantly (p < 0.01 and p < 0.05,
      respectively). The lipogenic enzymes showed decreased activity in the diabetic
      liver, while in kidney they showed an increased activity. When compared with the
      controls these changes were significant. The treatment of alloxan diabetic rats
      with MFE and SOV prevented these alterations and maintained all parameters near
      control values. Most effective prevention was however observed in a combined
      treatment of Momordica with a reduced dose of SOV (0.2%). The results suggest
      that Momordica fruit extract and SOV exhibit hypolipidemic as well as
      hypoglycemic effect in diabetic rats and their effect is pronounced when
      administered in combination.

PMID- 15724445
TI  - In-vitro dual binding activity of a evolutionarily related subgroup of hnRNP
      proteins.
AB  - The wide family of heterogeneous nuclear ribonucleoproteins (hnRNPs) comprises
      members that interact with single-stranded nucleic acids. On the basis of their
      structure, some of them are characterised by a tandem RNA-binding domain (RBD)
      and a glycine-rich C-terminus, showing a high degree of homology. Recently, we
      have isolated some proteins belonging to this group that interact with single
      stranded cytosine-block telomeric DNA. The aim of the present investigation is to
      better characterise the relationship of some structural features shared by these
      proteins and their in-vitro interaction with the telomeric type sequences. We
      analysed the in-vitro binding properties of some of these components toward both
      single-stranded telomeric motifs. Using deletion mutants, the relationship
      between cytosine-rich motif binding activity and the structural features of one
      of these proteins is further characterized. This binding activity appears to be
      related to a subgroup of the 2xRBD+Glycine rich hnRNP, suggesting functionally
      distinct properties of these proteins, in agreement with their evolutionary
      relationship.

PMID- 15724446
TI  - Inhibition of RIP2/RIck/CARDIAK activity by pyridinyl imidazole inhibitors of p38
      MAPK.
AB  - Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase (MAPK)
      have been used extensively in vitro and in vivo to investigate the role of p38 in
      physiological processes. As with other pharmacological inhibitors, non-specific
      targets of the p38 inhibitors have been reported. We have found that the protein
      kinase receptor interacting protein-2 (RIP2) is another target for the family of
      p38 inhibitors. The autophosphorylation of RIP2 was inhibited in vitro by the p38
      inhibitors SB220025, SB203580 and PD169316 at concentrations comparable to those
      used to inhibit p38. We also identified two new in vitro substrates for RIP2,
      myelin basic protein and histone H3 with apparent Km values of 2.1 microM and
      0.65 microM, respectively. The ability of RIP2 to phosphorylate these two
      substrates was sensitive to the p38 inhibitors as well. As was shown for
      p38alpha, a conserved threonine in the kinase domain of RIP2 is required for
      sensitivity to the inhibitors, indicating that the mechanism of inhibition of
      RIP2 is similar to that of p38. These results demonstrate that the pyridinyl
      imidazole inhibitors block RIP2 as well as p38 kinase activity.

PMID- 15724447
TI  - Oral supplementation of piperine leads to altered phase II enzymes and reduced
      DNA damage and DNA-protein cross links in Benzo(a)pyrene induced experimental
      lung carcinogenesis.
AB  - In recent years, considerable emphasis has been focused on identifying new
      chemopreventive agents, which could be useful for the human population. Piperine
      is a pure, pungent alkaloid constituent of black and long peppers (piper nigrum
      and piper longum), which is a most common spice used throughout the world. In the
      present study, we examined the protective role of piperine during experimental
      lung carcinogenesis with reference to its effect on DNA damage and detoxification
      enzyme system. The activities of detoxifying enzymes such as glutathione
      transferase (GST), quinone reductase (QR) and UDP-glucuronosyl transferase (UDP
      GT) were found to be decreased while the hydrogen peroxide level was increased in
      the lung cancer bearing animals. Supplementation of piperine (50 mg/kg bwt)
      enhanced the detoxification enzymes and reduced DNA damage as determined by
      single cell electrophoresis. Furthermore, the DNA-Protein cross links which was
      found to be high in lung cancer bearing animals was also modulated upon
      supplementation with piperine. Our present results explain the understanding of
      unique association between anti-peroxidative effect of piperine and ultimately
      the capability of piperine to prevent cancer.

PMID- 15724448
TI  - Time course studies on the initiation of complement activation in acute
      myocardial infarction induced by coronary artery ligation in rats.
AB  - This study attempted to probe the role of complement activation in promoting
      acute myocardial infarction (AMI) induced by coronary artery ligation (CAL) in
      rats. The surgical technique used in this study significantly reduced early
      mortality (95% survival rate) and also reduced the variation in infarct size
      (33+/-1.87%) at 32 h after surgery. Time course studies on the initiation of AMI
      at various time points were carried out using physiological, biochemical,
      histopathological and electron microscopical techniques. Serum markers and
      activities of lysosomal hydrolases were found to be significantly elevated at the
      8th hour post ligation. Histological studies showed polymorphonuclear cells
      emigration and total coagulation necrosis. Transmission electron micrograph
      exhibited mild distortion of muscle fibres and mitochondrial rupture with
      disrupted cristae. Immunoblotting studies confirmed the presence of alpha2
      macroglobulin which supported the inflammatory response at 8th h of post
      ligation. The initiation of the complement (C) activation was observed by the
      increase in the level of the soluble form of the membrane attack complex (sC5b-9)
      in serum and left ventricle. Immunoexpression studies confirmed the initiation of
      the terminal C activation as shown by the expression of C5, C6, C7, C8, C9 and
      sC5b-9 complex at the 8th h of AMI. This study conclusively demonstrated that
      initiation of the C activation was observed to be significant at the 8th h of AMI
      induced by CAL in rats.

PMID- 15724449
TI  - Removal of serum factors by charcoal treatment promotes adipogenesis via a MAPK
      dependent pathway.
AB  - In vitro differentiation of the progenitor cells or preadipocytes into adipocytes
      is usually achieved by adding an adipogenic mixture (isobutylmethylxanthine,
      dexamethasone, and insulin, IDI) to medium supplemented with fetal bovine serum
      (FBS). To study the effects of steroid hormones in vitro, endogenous hormones,
      growth factors and cytokines are removed by charcoal stripping of serum. However,
      the effects of charcoal-stripped serum (CS-FBS) per se on adipogenesis have been
      ignored. Here, we showed that alkaline phosphate activity and nodule formation of
      osteoprogenitor KS483 cells were lower in CS-FBS than in FBS. Concurrently,
      abundant amounts of adipocytes were only observed in KS483 cells cultured with CS
      FBS, irrespective of the brands of serum used. Inhibition of the p42/44 MAPK
      pathway by its specific inhibitor PD98059 increased adipogenesis of KS483 cells
      with FBS, whereas activation of this signalling pathway by EGF blocked
      adipogenesis of these cells with CS-FBS. Furthermore, the p42/44 MAPK
      phosphorylation of KS483 cells cultured with CS-FBS was decreased compared with
      FBS. We concluded that charcoal-stripping of serum removed stimulators of the
      MAPK signalling pathway and in turn led to downregulation of osteogenesis and
      upregulation of adipogenesis. Interestingly, the adipogenic mixture IDI
      stimulated adipogenesis of KS483 cells cultured with CS-FBS, but not with FBS.
      Furthermore, differential effects of genistein on adipogenesis were observed in
      KS483 cells cultured with FBS or CS-FBS in combination with IDI. Our results
      showed that charcoal stripping of serum affected the commitment of KS483 cells
      and therefore differentially regulated adipogenesis influenced by IDI alone and
      in combination with genistein.

PMID- 15724450
TI  - PKCepsilon inhibits the hyperglycemia-induced apoptosis signal in adult rat
      ventricular myocytes.
AB  - Recruitment of the protein kinase C (PKC) family of isozymes is an integral
      component of the signaling events that direct cardiac phenotype expressed during
      postnatal development and in response to pathologic stimuli. Hyperglycemia is a
      potent activating signal for cardiac PKC isozymes and induces the apoptosis
      program in cardiac muscle cells. To determine whether cardiac PKC isozymes
      modulate transmission of the hyperglycemia apoptosis signal, we have employed
      isozyme-specific peptide modulators to selectively inhibit (PKC betaI/betaII,
      zeta and epsilon) or activate (PKCepsilon). PKC peptides were delivered to
      primary cultures of serum starved adult rat ventricular myocytes (ARVM), by
      conjugation to the homeodomain of drosophila antennapedia. As expected,
      hyperglycemia induced a 35% increase in ARVM apoptosis. Peptide inhibitors of PKC
      betaI/betaII and zeta blocked transmission of the hyperglycemia apoptosis signal,
      whereas the isozyme specific inhibitor of PKCepsilon (epsilonV1-2) did not alter
      the magnitude of glucose-induced ARVM apoptosis. Alternatively, the PKCepsilon
      translocation activator (psi epsilonRACK) abolished hyperglycemia-induced
      apoptosis, strongly suggesting a cardioprotective role for PKCepsilon in this
      system. Therefore, we conclude that cardiac PKC isozymes modulate hyperglycemia
      induced apoptosis and activation of cardiac PKCepsilon protects ARVM from the
      hyperglycemia-induced death signal.

PMID- 15724452
TI  - Membership in capitated arrangements mirrors market trends.

PMID- 15724451
TI  - Signal transduction mechanisms involved in cardiac preconditioning: role of Ras
      GTPase, Ca2+/calmodulin-dependent protein kinase II and epidermal growth factor
      receptor.
AB  - It is well established that brief episodes of ischemia/reperfusion (I/R)
      [preconditioning (PC)] protect the myocardium from the damage induced by
      subsequent more prolonged I/R. However, the signaling pathways activated during
      PC or I/R are not well characterized. In this study, the role of Ras-GTPase,
      tyrosine kinases (TKs), epidermal growth factor receptor (EGFR) and
      Ca2+/calmodulin-dependent protein kinase II (CaMK II) in mediating PC in a
      perfused rat heart model was investigated. A 40-min episode of global ischemia in
      perfused rat hearts produced significantly impaired cardiac function, measured as
      left ventricular developed pressure (Pmax) and left ventricular end-diastolic
      pressure (LVEDP), and impaired coronary hemodynamics, measured as coronary flow
      (CF) and coronary vascular resistance (CVR). PC significantly enhanced cardiac
      recovery after IR. Combination of PC and FPT III (Ras-GTPase inhibitor FPT III;
      232 ng/min for 6 days) treatment did not produce any additive benefits as
      compared to PC alone. In contrast, PC-induced improvements in cardiac function
      after I/R were significantly attenuated by pretreatment with genistein
      (1mg/kg/day for 6 days), a broad-spectrum inhibitor of TKs, or AG1478 (1mg/kg/day
      for 6 days), a specific inhibitor of EGFR tyrosine kinase or KN-93 (578 ng/min
      for 6 days), a CaMK II inhibitor, before PC. These observations suggest that PC
      and FPT III pretreatment may produce cardioprotection via similar mechanisms.
      Present results also indicate that activation of TKs and specifically activation
      of EGFR-mediated TKs and CaMK II-mediated regulation of calcium homeostasis are
      part of the PC mechanisms that improve recovery after IR.

PMID- 15724453
TI  - Medical groups work to mitigate increases in operating costs.

PMID- 15724454
TI  - Even in mixed reimbursement environment, California group is a winner.

PMID- 15724456
TI  - More and sicker patients surviving coronary bypass surgery, study finds.

PMID- 15724455
TI  - Generics more common, but prescribing patterns still uneven.

PMID- 15724457
TI  - [Protective effect of Vipera raddei venom damage of peripheral nerve].
AB  - In rats, single pulse activity of inter- and motoneurons of the spinal cord
      lumbar segment was studied in stimulation of cut. n. ischiadicus, extensor (n.
      gastrocnemius) and flexor (n. peroneus communis) after treatment with the Viper
      raddei venom for 4 weeks. In the control rats, no responses occurred in the n.
      ischiadicus distal stump, whereas the responses to contralateral nerve
      stimulation did occur. On the intact side, the responses occurred in opposite
      sequence. The absence of effects of the cut nerve distal stump stimulation in
      control rats resulted from the coalescence absence in the proximal stump which
      suggests atrophy of the distal stump. Morphological data prove a distal stump
      hypertrophy and restoration of the affected limb motor activity. The findings
      suggest a possibility of application of the Viper raddei venom for regeneration
      of injured peripheral nerve.

PMID- 15724458
TI  - [Neurophysiological correlates of induced discrete emotions in humans: an
      individual analysis].
AB  - The present study addressed EEG pattering during experimentally manipulated
      emotion. Film clips previously shown to induce happiness,joy, anger, disgust,
      fear/anxiety, sadness, as well as neutral control films, were presented to 30
      university students while a 62-channel EEG was recorded, and a self-reported
      effect was described. Analyses revealed both emotion-specific and emotion
      unspecific EEG pattering for the emotions under study. Induced positive and
      negative emotions were accompanied by hemispheric activation asymmetries in theta
      2, alpha-2, and beta-1 EEG frequency bands. Emotions of joy and disgust induced
      lateralized a theta-2 power increase in anterior-temporal and frontal regions of
      the left hemisphere reflecting involvement of cognitive mechanisms in the
      emotional processing. Negative emotions of disgust and fear/anxiety were
      characterized by alpha-2 and beta-1 desynchronization of the right temporal
      parietal cortex, suggesting its involvement in modulation of the emotion-related
      arousal.

PMID- 15724459
TI  - [Evoked activity of the cat hypothalamus and amygdala under food motivation and
      in emotional stress].
AB  - Amplitude-latency characteristics of auditory evoked potentials (EPs) recorded in
      bilateral points of the lateral hypothalamus and amygdala were studied under food
      motivation, in emotional stress (presentation of dogs) and tentative reactions.
      In the state of hunger, as compared with safety, the latencies of P1, N2
      components of EP in hypothalamus, and P1, N2, N3 in amygdala were decreased and
      their amplitudes were changed. Changes in the left side of both structures were
      more pronounced. During presentation of dogs, decreases of latencies of all EP
      components including N1 occurred in hypothalamus and amygdala, changes in
      hypothalamic potentials were more pronounced on the right side, whereas in the
      amygdala--on the left side. During tentative responses to emotional-neutral
      stimuli, the latency of EP increased. It was concluded that sensory reactivity of
      hypothalamus and amygdala increased in motivational-emotional states. It was
      supposed that the side of dominance of structure may be related both to the
      factors of active or passive behavior during fear and the genesis of emotion
      (motivational or informational).

PMID- 15724460
TI  - [Participation of the neostriatum transmission system in automation of motor
      skills in dogs].
AB  - The study shows that, in spite of high criteria of performing inctrumental
      reflex, the ability to repeat the reflex performance, the increase in tonic
      component of the response, a dostinct diagonal pattern of posture readjustment,
      and the local (not diffuse) projection of the mass centre position upon
      tensoplatforms of anterior paws were only observed after a prolonged training
      that led to automation of the skill. The instrumental response automation effect
      could be obtained at once following a bilateral microinjection of carbacholine
      into the neostriatum. The same albeit a weaker effect could be obtained with
      bilateral microinjections of D2 Dopamine receptor blocking agent Raclopride into
      the neostriatum. Bilateral injections of Pyrenzepine yield an opposite result: an
      increase in the physical component of the response < a disorder in the diagonal
      pattern of posture readjustment, and a diffuse nature of projection of the mass
      centre position of anterior paws on tensoplatforms. Indirect efferent output of
      the neostriatum seems to play an important role in motor instrumental reflex as
      well as in the process of automation of the motor skill.

PMID- 15724461
TI  - [Compensatory hypertension and fetal heart remodeling: from adaptation to
      pathology].
AB  - Left ventricular (LV) isovolumetric relaxation time (IRT), shape and LV wall
      movement uniformity were assessed in 102 appropriate for gestational age (AGA)
      human fetuses and 36 fetuses with intrauterine growth retardation (IUGR). In 28
      AGA newborns and 26 IUGR infants rennin and angiotensin 1 concentrations were
      assessed in umbilical cord blood by radioimmunoassay. Systolic blood pressure
      (BP) was also measured in these infants. The IRT in IUGR fetuses was more (50.9+/
      8.6 ms) than in the AGA fetuses (42.8+/-6.7 ms, p < 0.01). The mean BP in the
      IUGR newborns was greater (76+/-5 mm Hg vs 60+/-6 mm Hg, p < 0.01) than in the
      AGA fetuses. Rennin and angiotensin 1 concentrations were 1.61- and 1.56-fold
      greater in the blood of the IUGR newborns than in the AGA infants. A chronic
      hypertension in placenta perfusion increase in the IUGR fetuses was proposed. The
      changes in LV shape and uniformity of wall movement (remodeling) are considered
      to be the result of chronic increase in afterload. Rennin-angiotensin activation
      and LV remodeling as an adaptive reactions of antenatal period could promote the
      arterial hypertension development in later life.

PMID- 15724462
TI  - [The functional state classification and evaluation of the stability level in
      mental loads based on the factor structure of heart rate variability parameters].
AB  - In the paper, outcomes of the researches devoted to factor analysis of heart rate
      variability parameters and definition of the most informative parameters for
      diagnostics of functional states and an evaluation of level of stability to
      mental loads, are presented. The factor structure of parameters, which unclude
      integral level of heart rate variability (1), balance between activity of vagus
      and brain cortical-limbic systems (2), integrated level of cardiovascular system
      functioning (3), is substantiated. Factor analysis outcomes have been used for
      construction of functional state classification, for their differential
      diagnostics, and for development and check of algorithm for evaluation of the
      stability level in mental loads.

PMID- 15724464
TI  - [Dependence of myocardial contracture on energy resources during the calcium
      paradox].
AB  - Perfusion of the rat isolated hearts with calcium-free and calcium containing
      solution revealed a complex and deep myocardial damage called the calcium
      paradox. The reperfusion of the rat heart with calcium rich media resulted in
      myoglobin loss from the heart, significant decreasing of ATP and phosphocreatine
      level, complete uncoupling of respiration and phosphorylation in mitochondria,
      occurrence of myocardial contracture. Decreasing of sodium level to 30 mM--80 mM
      in calcium free media exacerbates the heart damage due to the calcium paradox
      with absence of contracture. Addition of phosphocreatine (1 mM, 5 mM, 10 mM)
      evoked some restoration of ATP contents in the tissue with appearance of
      significant contracture. Phosphocreatine exacerbated the loss of myoglobin from
      the heart subjected to the calcium paradox. A discrepancy between myocardial
      contracture and degree of cellular damage has been observed during the calcium
      paradox.

PMID- 15724463
TI  - [Effect of chronic psychoemotional stress on subpopulation spectrum of T
      lymphocytes in immunocompetent organs in male mice].
AB  - Subpopulation spectrum of T lymphocytes (CD3+, CD4+, CD8+, CD25+, and CD3(+)25+)
      in thymus, spleen and inguinal lymphatic nodes have been studied in male mice
      after 20 days of psychoemotional stress produced by social defeats in daily
      agonistic confrontations. A reduction of total number of cells, of absolute
      numbers of all researched subpopulations of lymphocytes and % CD3+ cells in
      thymus of submissive mice was shown in comparison with intact animals. Reduction
      of total number of splenocytes and absolute numbers of CD4+ and CD8+ lymphocytes
      has been observed in a spleen of submissive mice. Besides, % CD3+, CD25+, CD4+
      and CD25+ cells were increased in these animals in comparison with intact mice.
      The absolute number of cells with CD8 phenotype was increased in inguinal
      lymphatic nodes. The data obtained suggest that the chronic psychoemotional
      stress is accompanied by serious changes of the cellular link of immunity. The
      effect of chronic emotional social stress on mutual interaction of the central
      and peripheral links of immunity has been discussed.

PMID- 15724465
TI  - [Skeletal muscle blood bed in growing rats].
AB  - Morphometric study of vascular bifurcations and capillaries in biceps femoris
      artery basin was performed in 2-week old, 1-month old, and adult Wistar rats.
      Proceeding from the results, the blood tree was digitally reconstructed, and the
      main haemodynamic parameters in digital simulation were evaluated in this
      vascular bed: the blood flow velocity, wall shear stress, drop of perfusion
      pressure, and resistance. The comparison with a similar study of cerebral
      vascular bed revealed peculiarities of the vascular bed formation and intraorgan
      haemodynamics in these organs.

PMID- 15724466
TI  - [A change in the alarm level entails a change in behavioural strategy of mice in
      stress and a change in analgesia induced by it].
AB  - The effects of anxiogenic (pentylentetrazole) and anxiolytic (diazepam) agents on
      <<behavioral despair>> and cold swim stress-induced analgesia were investigated
      in SHR and NMRI male mice. It was shown that behavioral response to acute stress
      was associated with a change in the pain tolerance threshold. Diazepam increased
      immobility time and attenuated stress-induced analgesia (SIA). NMRI mice were
      more responsive to anxiolytic than the SHR mice, but the lattes manifested more
      dramatic changes when anxiety was pharmacologically enhanced (immobility time was
      significantly reduced and the SIA exaggerated). Our findings suggest that the
      main parameters change in reciprocal manner following a pharmacologically altered
      anxiety, and reveal that differences between two strains of mice are determined
      by differences in their sensitivity to stress.

PMID- 15724467
TI  - [Reaction of alpha-actinin from renal inner medulla on prolonged dehydration].
AB  - A western-blot analysis using monoclonal antibodies revealed that a reduction of
      alpha-actinin occurred in the renal inner medulla under the long-lasting
      dehydration. The ratio between protein content measured in rats of WAG line being
      hydrated or after 3-days water deprivation consisted of 52.7+/-6.2 against 23.9+/
      3.3 as evaluated in relative units. The alpha-actinin level changes similarly in
      mutant rats of Brattleboro line not capable of synthesizing vasopressin. It was
      57.5+/-4.6 in hydrated animals, and statistically lower in rats being under 3-day
      water deprivation--26.4+/-5.7 in relative units of protein.

PMID- 15724469
TI  - [Off-pump versus conventional coronary artery bypass grafting in octogenarians].
AB  - Coronary artery bypass grafting (CABG) in elderly patients is becoming
      increasingly common. From January 1996 to February 2002, 836 patients underwent
      CABG in our hospital, of whom 33 patients (3.9%) were aged 80 years or older. We
      evaluated the clinical and short-term results of 7 cases of off-pump CABG (OPCAB)
      and 26 cases of conventional CABG (C-CABG). Mean patient age and preoperative
      risk factors were similar in both groups. The OPCAB group had significantly
      decreased operation time (218 versus 281 minutes, p<0.05), and the number of
      distal anastomoses was significantly fewer in the OPCAB group than in the C-CABG
      group (1.9 versus 3.8, p<0.05). The frequency of complete revascularization in C
      CABG was significantly higher than that of the OPCAB group (84.6% versus 42.9%,
      p<0.05), and there were no differences in the incidence of major postoperative
      complications between the groups. There was no hospital death in either group.
      Cumulative cardiac event free rates were 75% at 1 year and 75% at 3 years in the
      OPCAB group and 100% at 1 year and 84.6% at 3 years in the C-CABG group (p<0.05).
      In conclusion, CABG is safe and effective for myocardial revascularization in
      octogenarians. Except for high-risk cases, complete revascularization with OPCAB
      or C-CABG should be performed, because favorable outcomes can be expected even in
      the elderly patients.

PMID- 15724468
TI  - [Clinical experience with aortic connector system].
AB  - From April to December 2002, 40 patients underwent coronary artery bypass
      grafting (CABG) using the St. Jude Medical (Minneapolis) Symmetry bypass system
      (aortic connector system: ACS). 59 proximal anastomoses (51 saphenous vein
      grafts, 8 radial artery grafts) were performed with the ACS. One saphenous vein
      graft occluded during operation. Postoperative evaluation of the anastomotic
      patency was carried out by angiography in 45 grafts. Five of the saphenous vein
      grafts were occluded (5/38). One patient who was shock state before operation
      presented with postoperative unconsciousness. Another patient died at 8th
      postoperative day caused by ventricular fibrillation. We conclude that the ACS
      produces a simple, quick way of performing the proximal anastomosis without the
      need for clamping the aorta, allows reducing risk of embolization by aortic
      manipulation. However, it is necessary to discuss sufficiently using the ACS,
      because the graft patency with the ACS is lower than with standard suturing
      technique.

PMID- 15724470
TI  - [Pulmonary metastasis from colorectal cancer with hepatic metastasis].
AB  - We have investigated cases where pulmonary metastasis from colorectal cancer was
      resected during the last 15 years, comparing a group with liver metastasis [LM
      (+)] to a group without liver metastasis [LM (-)]. The following are the
      characteristics of the LM (+) versus LM (-) groups. Gender: male 6, female 5
      versus male 9, female 11, age: 61.4+/-11.4 versus 63.9+/-9.4 years, number of
      lung metastasis: 1.42 versus 1.29, duration of primary-lung metastasis: 1.59+/
      1.02 versus 2.55+/-1.46 years, preoperative CEA: 69.3+/-71.1 versus 8.64+/-5.63
      ng/ml, ratio of bilateral lung metastasis: 23.0 versus 4.8%, more than 1 ratio of
      pulmonary metastasis: 38 versus 19%, complete resection ratio of pulmonary
      metastasis: 84.6 versus 100%, ratio of thoracoscopic surgery: 69.2 versus 66.7%,
      and 2-year survival ratio: 63 versus 78%. There were no statistically significant
      differences in these values between the LM (+) and LM (-) group. A larger number
      of cases and follow-up duration will be required in the future; we think that the
      resection of pulmonary metastasis from colorectal cancer with liver metastasis
      can be supported for the present.

PMID- 15724471
TI  - [Midterm restenosis of freestyle valved conduit in an adult tetralogy of Fallot].
AB  - We report a case of midterm restenosis of freestyle valved conduit implanted
      between the right ventricle and the pulmonary artery. A 69-year-old woman visited
      our hospital with dyspnea and general fatigue and was diagnosed as tetralogy of
      Fallot. Total corrective surgery including patch closure of ventricular septal
      defect was performed using the freestyle valve with the Hemashield prothesis to
      reconstruct the right ventricle to the pulmonary artery. The catheterization
      revealed almost normal right ventricular pressure on 40th postoperative day, but
      the opening of the valve was limited. Twenty-two months later she visited our
      hospital with severe right heart failure. The pressure gradient over the valve
      was 122 mmHg and the leaflet of the freestyle valve was markedly thickened
      causing severe stenosis. Use of the freestyle valve for the right ventricular out
      flow tract reconstruction has to be further studied.

PMID- 15724472
TI  - [Traumatic lung cyst].
AB  - INTRODUCTION: Traumatic lung cysts have been reported to be comparatively rare.
      However, we diagnosed 11 cases to have traumatic lung cyst over the past 6 years.
      We mainly present the most characteristic 3 cases and also discuss our findings
      for the 11 cases of traumatic lung cyst. CASE 1: A 17-year-old male, who was
      injured on his left chest after falling from a height of 7 m. He presented in a
      state of shock and was immediately resected the left lung because of massive
      bleeding from a damage of pulmonary vein. However, he finally died due to
      disseminated intravascular clotting (DIC). We recognized a large traumatic lung
      cyst, which went from the upper lobe to lower lobe thoroughly the resected lung.
      CASE 2 : A 19-year-old male, who was injured on his left chest in traffic
      accident. We recognized a wide contusion, cysts and hemorrhage in the left upper
      lobe on computed tomography (CT) findings. We performed an emergency left upper
      lobectomy because of the intrabronchial bleeding. CASE 3: An 11-year-old boy,
      suffered trauma on his right chest when he fell while walking. We recognized
      minor redness and subcutaneous emphysema in the injured are, in addition to a
      contusion and cyst in the right lower lobe on CT findings. He was conservatively
      observed, and both the cyst and contusion gradually contracted. CONCLUSION:
      Regarding traumatic lung cysts, a quick diagnosis and timely selection of the
      optimal treatment are important. When a pulmonary injury is serious, then quick
      surgical treatment is necessary, and a close follow-up is necessary in case
      undergoing conservative treatment.

PMID- 15724473
TI  - [Clinicopathologic study of thymic epithelial tumors].
AB  - OBJECTIVE: We analyzed clinicopathologic characters and long-term results of 11
      thymic epithelial tumors. METHODS: Five cases of thymic carcinoma and 6 cases of
      thymoma treated in our hospital from September 1991 to June 2002 were
      retrospectively analyzed. RESULTS: The histological subtypes of thymic carcinoma
      were basaloid carcinoma in 2 cases, epidermoid non-keratinizing carcinoma in 1
      case, undifferentiated carcinoma in 1 case and sarcomatoid carcinoma in 1 case.
      Four cases underwent chemotherapy and radiotherapy. Three cases underwent
      midsternal thoracotomy, 1 had total resection and 2 had exploratory thoracotomy
      due to tumor invasion of the right upper lobe and cardiac sac. Two cases of
      basaloid carcinoma had been alive more than 10 years since the operation. The
      histological subtypes of thymoma were 1, 2, 1, 1 and 1 cases with type A, AB, B
      1, B 2 and B 3. All cases underwent midsternal thoracotomy, 4 cases had
      thymothymectomy and 2 cases had extended thymothymectomy. Five cases have been
      alive since the operation. Strong immunoreactivity for bcl-2 and p 53 expression
      of epidermoid non-keratinizing carcinoma and undifferentiated carcinoma were
      seen. ki-67 labeling index of epidermoid non-keratinizing carcinoma and
      undifferentiated carcinoma and type B 3 thymoma were higher than those of the
      other carcinomas and thymomas.

PMID- 15724474
TI  - [Sandwich technique for closing of the large muscular Swiss-cheese type
      ventricular septal defects].
AB  - A 9-year-old girl, who has had a diagnosis as a Taussig-Bing anomary, underwent
      an original Jatene procedure (o-J) 2 months after birth. This time, she had a
      diagnosis of the muscular multiple ventricular septal defects (mVSD) and
      pulmonary stenosis after o-J. The mVSD was Swiss-cheese type and was large from
      the proximal of the infundibular septum to the apex and posterior of the septum.
      It was closed by the sandwich technique using a pair of felt patches, which of
      one was placed at right ventricular side and the other was at left ventricular
      side, slightly larger than the whole area of the mVSD. The patch fixation was
      placed with 1 stitch at the center between the patches and a few stitches around
      the right ventricular side patch to the ventricular septum. Postoperative cardiac
      function was uneventful regardless of the very large patches placed at the
      ventricular septum and the cardiac catheterization after 1 year postoperatively
      showed the pulmonary/systemic blood flow ratio was 1.0. This technique for the
      closure of the large Swiss-cheese type mVSD can be considered to be very
      effective.

PMID- 15724475
TI  - [Autologous fibrin sealant preparing system in coronary artery bypass grafting].
AB  - Autologous fibrin sealant (AFS) which is not based on the conventional method of
      co-administering fibrinogen, thrombin and aprotinin was prepared by Vivostat
      system, and was used in coronary artery bypass grafting (CABG). The purpose of
      this study was to investigate the safety and efficacy of the AFS prepared by the
      Vivostat system. In 6 of 68 cases of CABG, normal AFS was not prepared due to
      device failures. AFS was prepared and sprayed in 62 cases. There were the total
      of 230 anastomosis sprayed AFS and the bleeding could not seen in 225
      anastomosis. Surgical hemostatic procedures (4 cases) were or other sealant usage
      (1 case) was performed 5 bleeding anastomosis sites. The rate of hemostasis at
      the anastomosis using AFS was 97.8%. This study was conducted in patients
      undergoing CABG. In this group of patients, a number of commercial available
      fibrin sealant products are routinely used. The usefulness of Vivostat as medical
      device to prepare and administer AFS was confirmed in this study.

PMID- 15724476
TI  - [Asplenia syndrome with total anomalous pulmonary venous connection].
AB  - Three patients of asplenia syndrome with total anomalous pulmonary venous
      connection (TAPVC) were reported. Case 1 with exceeding pulmonary blood flow,
      underwent TAPVC repair and pulmonary artery banding as a first palliation before
      bi-directional Glenn shunt. Case 2 did not require any surgery to control the
      pulmonary blood flow before the simultaneous procedure of TAPVC repair and bi
      directional Glenn shunt. Case 3 with decreased pulmonary blood flow underwent a
      complicated course with 3 times of Blalock-Taussig shunts and the repair of TAPVC
      to prepare for bi-directional Glenn shunt. Simultaneous repair of TAPVC with the
      procedure which aimed to control the pulmonary blood flow at the first palliation
      surgery will simplify the control of pulmonary blood flow and prepare good
      condition of the lung for the Fontan operation in the future.

PMID- 15724477
TI  - [Abdominal organ infarction encountered immediately after surgery of primary lung
      cancer].
AB  - Very rare cases of abdominal organ infarction after surgery of primary lung
      cancer were reported. Case 1: Patient 1 was a 70-year-old man who underwent left
      upper lobectomy and ND 2a in June 1999 based on the clinical diagnosis of stage
      IA lung cancer. On the 4th postoperative day, the patient developed fever and
      right flank pain. Abdominal computed tomography (CT) demonstrated a specific
      finding compatible with renal infarction. The etiology could not be determined.
      The patient was treated conservatively. However, severe atrophy of right kidney
      was demonstrated by following CT performed 3 years later. Case 2: Patient 2 was a
      70-year-old woman who underwent left upper lobectomy and ND 2a in December 2002
      based on the clinical diagnosis of stage IA lung cancer. On the 4th postoperative
      day, the patient developed abdominal pain in the left upper quadrant, nausea and
      vomiting which had lasted for 10 days. Abdominal CT demonstrated a wedge-shaped
      filling defect at spleen compatible with splenic infarction. The etiology could
      not be determined. The patient was treated conservatively with prophylactic
      antibiotic therapy and followed closely. Partial atrophy of spleen was
      demonstrated by following CT performed 4 months later.

PMID- 15724478
TI  - [Successful resection of left ventricular myxoma in a toddler; report of a case].
AB  - A 4-year-old girl was found to have large left ventricular myxoma without any
      tumor-related symptoms. She underwent an urgent surgery and the myxoma was
      successfully removed through a left ventriculectomy. Great care was taken to
      prevent tumor-embolization during surgery, and to resect the endocardium
      attaching directly to the tumor. Future surveillance of this case warrants our
      operative technique described in this report.

PMID- 15724479
TI  - [Simultaneous operation for annulo-aortic ectasia and mitral regurgitation in a
      patient with non-Marfan syndrome; report of a case].
AB  - A 74-year-old woman with non-Marfan syndrome underwent aortic root replacement
      and mitral valve replacement simultaneously for annulo-aortic ectasia and mitral
      regurgitation. Postoperatively, she suffered from cholecystitis and underwent
      percutaneous transhepatic gull bladder drainage. After this intervention, her
      postoperative recovery was uneventful. The purpose of this study is to suggest
      the possibility of mitral regurgitation due to annular enlargement of the mitral
      valve as an outcome of deterioration of the annulo-aortic ectasia.

PMID- 15724480
TI  - [Staged operation of off-pump coronary artery bypass grafting using aortic
      connector system, and concomitant surgery for abdominal aortic aneurysm and
      gastric cancer; report of a case].
AB  - Recently the patient of the atherosclerotic disease associated with malignant
      disease has been increased. A 75-year-old man was referred to our section with an
      infrarenal abdominal aortic aneurysm (AAA) and a gastric cancer (GC).
      Preoperative coronary angiogram revealed the significant stenoses of the right
      coronary and the left anterior descending coronary artery. We selected the staged
      operation of off-pump coronary artery bypass grafting (CABG) [OPCAB] and the
      concomitant surgery for the AAA and the GC. Operative invasion could decrease
      with the surgical procedure of the OPCAB and the concomitant surgery compared to
      the conventional CABG or the separate operation. We used the aortic connector
      system during OPCAB to prevent such the serious complications of the aortic
      dissection or the systemic embolism due to the calcified ascending aorta.

PMID- 15724482
TI  - [Multiple synchronous intrathoracic neurilemmomas who had a past history of
      neurilemmoma on the abdominal wall; report of a case].
AB  - A 66-year-old female, who had received a surgery of the neurilemmoma on the
      abdominal wall 6 years ago, was referred to our hospital because of a chest X-ray
      abnormality. Chest computed tomography (CT) revealed 3 tumors in the left chest
      wall. One tumor arised from the 7th intercostal nerve and 2 tumors from 8th
      nerve. These tumors were surgically removed by video-assisted thoracic surgery.
      These tumors are histopathologically diagnosed as neurilemmoma and have the same
      characteristics with previously resected abdominal wall tumor.

PMID- 15724481
TI  - [Hemothorax associated with congenital pulmonary arteriovenous fistula; report of
      a case].
AB  - A 20-year-old man was admitted to our hospital with a sudden onset of dyspnea,
      caused by right pleural effusion. The patient was in a state of shock.
      Thoracentesis was revealed hemothorax. Right thoracotomy revealed pulmonary
      arteriovenous fistula projecting into the intrapleural space from the right upper
      lobe. Partial resection was performed. His postoperative course was uneventful.
      Intrapleural rupture of pulmonary arteriovenous fistula was reported rarely;
      therefore we described here our case.

PMID- 15724483
TI  - [Extralobar pulmonary sequestration with aberrant lobulation of the lower lobe;
      report of a case].
AB  - An adult case of extralobar pulmonary sequestration with aberrant lobulation of
      the right lower lobe is reported. A 32-year-old woman admitted to our hospital
      with a right intrathoracic tumor in the chest computed tomography (CT). Chest CT
      showed a mass lesion on the right diaphragm of a diameter 5 cm and abnormal
      fissure of the right lower lobe. Under the diagnosis of pulmonary sequestration
      without clearly thick vessels, video-assisted thoracoscopic surgery was
      performed. The mass existed between the right diaphragm and posterior lower lobe
      with a thin stalk, and the lower lobe had aberrant lobulation. The resected mass
      was histopathologically diagnosed as extralobar pulmonary sequestration.

PMID- 15724484
TI  - [Non-tuberculous mycobacterial infection along the staple-suture line after
      segmentectomy for small peripheral lung cancer; report of a case].
AB  - A 60-year-old non-immunocompromised man who had undergone right upper lobectomy
      and subsequent left superior segmentectomy for small peripheral lung cancers
      (stage I well-differentiated adenocarcinomas) 2 years earlier, was referred to us
      for further investigation of an asymptomatic abnormal shadow observed on a chest
      radiograph. Chest computed radiography showed air-space consolidation along the
      staple-suture line associated with the left superior segmentectomy, the
      abnormality was 4 x 5 x 5 cm. Completion lower lobectomy was performed because
      transbronchial biopsy did not provide for a definite diagnosis. Pathological
      examination revealed a large granuloma infected by Mycobacterium intercellulare.
      The lung parenchyma may be exposed along the staple-suture line and somewhat
      vulnerable to infection in cases of partial pulmonary resection. We should be
      aware of this possibility after lesser pulmonary resection for small peripheral
      lung cancer.

PMID- 15724485
TI  - [Pulmonary suture granuloma with Aspergillus after partial resection for lung
      cancer; report of a case].
AB  - We reported an extremely rare case of suture granuloma using monofilament nylon.
      A 76-year-old female had suffered from cough for 1 month. She had undergone
      partial resection for pulmonary squamous cell carcinoma 2 years previously. Chest
      X-ray and computed tomography (CT) detected a mass shadow adjacent to the
      previous surgical repair, and local recurrence of carcinoma was suspected.
      Thoracotomy was performed. Incisional biopsy revealed no recurrence sign,
      therefore partial resection was performed. Histopathological study and bacterial
      culture resulted suture granuloma with Aspergillus. The granuloma was caused not
      by foreign body reaction but by transbronchial infection. This case emphasizes
      that suture granuloma as pseudotumor may be indistinguishable from recurrent
      cancer.

PMID- 15724487
TI  - [Development of analysis of drugs and toxic substances that can play an immediate
      role in emergency medical service: what is to be analyzed?].
AB  - Our laboratory was capable of analyzing less than 20 drugs and toxic substances
      at the time of the establishment of the Center in 1994. Since the poisoning
      crimes in 1998, such as the curry poisoning with arsenic in Wakayama, the sodium
      azide poisoning in Niigata, and the potassium cyanide poisoning in Nagano, we
      have introduced methods for rapid qualitative analysis of arsenic compounds,
      cyanides and azides, and developed methods for qualitative analysis of three
      types of surfactants (cationic, anionic, and nonionic) on the basis of the
      statistics for intoxication patients transferred to the Center. In 1999, the
      Analysis Method Investigation Committee of the Japanese Society for Clinical
      Toxicology requested individual medical institutions to analyze 15 selected
      intoxicating substances, focusing on the following three aspects. 1. Intoxication
      with a high degree of fatality. 2. Intoxication where analysis plays an immediate
      role in treatment. 3. Intoxication with a high frequency of requests by clinical
      physicians for analysis. The selected substances included methanol, barbital
      drugs, benzodiazepines, tricyclic or tetracyclic antidepressants,
      methamphetamine, acetaminophen, salicylic acid, bromovalerylurea,
      organophosphorus pesticides, carbamate pesticides, paraquat, glufosinate,
      cyanides, arsenic, and theophylline. Responding to the Committee's request, out
      laboratory has been making efforts so that analysis of drugs and intoxicating
      substances can play an immediate role in emergency medical service, giving the
      highest priority to the aforementioned 15 substances. As a result, anyone of us
      can now rapidly analyze about 35 substances, including those listed by the
      Society, day and night.

PMID- 15724486
TI  - [Case of primary biliary cirrhosis patient with anti-p97/VCP antibodies
      presenting a mild clinical course].
AB  - In this study, we present a case of mild PBC that had anti-p97/VCP. A 53-year-old
      woman had been suspected of having chronic liver disease since 1983. In 1998, she
      visited the clinic, complaining of struma and pruritus. Laboratory findings on
      the first visit showed elevated levels of alkaline phosphatase (ALP) 454 IU/l(110
      360), gammaGTP 250IU/l(-45) and IgM 671mg/dl(35-220). A screening of anti
      mitochondrial antibody test was positive at a 1:80 dilution. A liver biopsy
      specimen revealed PBC at Scheuer stage 1. Following a treatment of ursodeoxycolic
      acid (UDCA) 300mg/day for 6 months, AMA and IgM were reduced to 1:20 and
      220mg/dl, respectively. However, she was found to have low titer of anti-p97/VCP
      antibodies, determined by immunoprecipitation of radiolabeled recombinant protein
      produced by in vitro translation and transcription of the full length p97 cDNA.
      She has continued to be clinically stable following administration of UDCA 300mg.
      A PBC patient with anti-p97/VCP antibody showed a milder clinical course,
      suggesting some beneficial role of this antibody.

PMID- 15724488
TI  - [Teaching of self-monitoring blood glucose to diabetic outpatients].
AB  - To improve the guidance for medical care of patients with diabetes, a system for
      certified diabetes educators in Japan has been started. Self-monitoring of blood
      glucose is a guidance service conducted for the treatment of diabetes performed
      by medical technologists. This approach is effective in motivating patients to
      perform self-control, and guidance that is useful for the improvement of
      patients' lifestyle as well as instruction of the operation of measurement
      apparatus is required. To achieve this goal, it is necessary to give a guidance
      in stages corresponding to the condition of the patient. Medical technologists
      will be able to participate in team treatment of diabetes by giving such
      guidance.

PMID- 15724489
TI  - [The ideal form of laboratory information management].
AB  - In a clinical laboratory, not many staff can point out the problems of laboratory
      information management. Although the clinical laboratory introduced information
      systems in early stage, no organization supplies specialists to this field. Much
      knowledge is hidden in the clinical laboratory data, which can be discovered by
      data-mining technology. We can contribute to medical development with this
      technology. Moreover, the cost of routine work and research work may also be
      mitigated. However, data-mining technology including structurally recorded data
      and diversified analytic systems are required to build such capability. The
      laboratory information management division should make sufficient use of the
      formal information with non-fixed data base searching. This section should become
      an important section in the hospital by supplying advanced knowledge discovery
      and strategic decision-making. In this paper, we discuss the necessity of the
      information education in the clinical laboratory field and describe the
      importance of information management in a clinical laboratory.

PMID- 15724490
TI  - [Liquid handling with mechanical pipettes].
AB  - Dispensing very small amounts of liquid is essential in all science fields. A
      wide range of pipetting systems is now available, including air-cushion pipettes
      and positive-displacement pipettes. The precision and accuracy depends on not
      only the principle of pipetting systems but vapor pressure, density, viscosity or
      wetting behavior of the solution. Preventing contamination is also important
      issue. Basically, we should handle these pipettes according to maker's
      instruction manuals.

PMID- 15724491
TI  - [Nuclear abnormalities in Pelger-Huet anomaly; progress in blood cell
      morphology].
AB  - Gene abnormalities responsible for familial Pelger-Huet anomaly have been
      recently discovered. Abnormalities in sequence of Lamin B Receptor(LBR) gene
      results in a lack of LBR protein that is essential for chromatin-binding to
      nuclear membrane. In neutrophils lacking LBR protein shows abnormal bilobular or
      monolobular nuclear forms and hyper-condensed chromatin-aggregation. We re
      analyzed distribution of such Pelger-Huet anomaly in other cell lineages; we
      found that not only neutrophils but erythroblasts, monocytes, lymphocytes, plasma
      cells, eosinophils and basophils are also carrying chromatin-hypercondensation.
      One third of megakaryocytes are also binucleated like neutrophils. We compared
      neutrophil morphology between familial Pelger-Huet anomaly and so called pseudo
      Pelger-Huet anomaly observed in patients with myelodysplastic syndromes(MDS) and
      acute myeloid leukemia(AML). The neutrophils in MDS were much similar to those of
      the familial anomaly, but neutrophils of AML, such as t (8;21) M2-AML and t
      (15;17) M3-AML, showed more heterogeneous pattern in lobulation and chromatin
      hypercondensation. Especially in M3, differentiation-induction by all-trans
      retinoic acid induced a marked neutrophilia with pseudo-Pelger-Huet anomaly
      without chromatin-hypercondensation. Lack of LBR protein in familial Pelger-Huet
      anomaly results in hypolobulation and chromatin-hypercondensation in neutrophils,
      but in other cells such as erythroblasts and lymphocytes only chromatin
      hypercondensation can be observed. In contrast pseudo-Pelger-Huet anomaly are
      more heterogeneous in morphology compared to the familial anomaly. The lack of
      leukemic or MDS transformation in the familial anomaly is a sharp contrast to the
      neoplastic nature of the pseudo-Pelger-Huet anomaly. In conclusion, our
      morphological recognition of certain abnormality of cells shows an marked
      progression when genetic abnormality responsible for some of them are discovered,
      and often make us recognize a further heterogeneity in them. We, hematologists
      and technicians, must be well prepared to report our own observation of an un
      explained morphological abnormality.

PMID- 15724492
TI  - [New era of cardiac stem cell therapy in heart failure].
AB  - Despite of plethora of reports on stem cell transplantation leading to
      neovascularization in infarct models, whether sustaining clinical benefit in post
      myocardial infarction patients is manifested by myocyte repair remains unclear.
      Cardiac muscle regeneration in adult heart is thought to occur through the
      mobilization and differentiation of mesenchymal stem cells in bone marrow origin,
      however, recent studies have suggested that substantial cardiac stem cells may
      exist in the heart itself, repopulating the damaged cardiac muscle during injury
      or aging processes. The implications of cardiac stem cells-based myocyte
      plasticity have recently begun to define in human heart, neither arisen from bone
      marrow nor circulating precursors. Introduction of cardiac stem cells may improve
      myocardial function, but several hurdles exist and should be coaxed far beyond
      the clinical application of cardiac regenerative therapies. On-going
      investigations may lead to the discovery of mediators of cardiac stem cells
      migration, proliferation and differentiation that, in turn, might result in the
      mending of the broken heart after injury.

PMID- 15724493
TI  - [Circulating progenitors contribute to angiogenesis, vascular repair, and lesion
      formation].
AB  - Atherosclerosis is responsible for more than half of all deaths in western
      countries. Numerous studies have reported that exuberant accumulation of smooth
      muscle cells plays a principal role in the pathogenesis of vascular diseases. It
      has been assumed that smooth muscle cells derived from the adjacent medial layer
      migrate, proliferate and synthesize extracellular matrix. Although much effort
      has been devoted, targeting migration and proliferation of medial smooth muscle
      cells, no effective therapy to prevent occlusive vascular remodeling has been
      established. Recently, we reported that bone marrow cells substantially
      contribute to the pathogenesis of vascular diseases, in models of post
      angioplasty restenosis, graft vasculopathy and hyperlipidemia-induced
      atherosclerosis. It was suggested that bone marrow cells may have the potential
      to give rise to vascular progenitor cells that home in the damaged vessels and
      differentiate into smooth muscle cells or endothelial cells, thereby contributing
      to vascular repair, remodeling, and lesion formation. This article overviews
      recent findings on circulating vascular precursors and describes potential
      therapeutic strategies for vascular diseases, targeting mobilization, homing,
      differentiation and proliferation of circulating progenitor cells.

PMID- 15724494
TI  - [Lung function testing --the Official Guideline of the Japanese Respiratory
      Society].
AB  - This review article introduces the official guideline for the lung function
      testing firstly established by the Japanese Respiratory Society in November 2004.
      The members of the Japanese Society of Laboratory Medicine were also included in
      the working group to make the guideline. A central goal of the guideline is to
      standardize the skill of lung function testing and thus minimize its variability.
      The guideline includes the chapters for spirometry, flow-volume curve, and
      diffusing capacity of the lung, where principles and quality controls are
      introduced with reference values for each testing. Furthermore, the algorithm for
      differential diagnosis using the lung function testing is demonstrated in the
      last chapter. The lung function testing can bring a strong impact on patients'
      lifestyle and future treatment plan. We sincerely hope that this guideline will
      contribute to routine laboratory practice.

PMID- 15724495
TI  - Beneficial effects of plasmapheresis before thymectomy on the outcome in
      myasthenia gravis.
AB  - OBJECTIVE: Since 1980, we have performed plasmapheresis before thymectomy for
      patients with generalized symptoms in order to protect against myasthenic crisis
      and to improve patient outcomes after thymectomy. The aim of this study was to
      evaluate an immediate and a long-term results of plasmapheresis before thymectomy
      for myasthenia gravis, retrospectively. METHODS: Between January 1980 and
      December 1997, 51 patients with Osserman class IIA or IIB symptoms were treated
      with transsternal thymectomy. Nineteen patients (group 1) were treated with
      plasmapheresis before thymectomy and 32 patients (group 2) were treated with
      thymectomy alone. RESULTS: In group 1, the time of plasmapheresis prior to
      thymectomy was 3.2 +/- 1.5. Nine (28.1%) patients in group 2 had crisis within 1
      year after thymectomy as compared with only one (5.3%) patient in group 1 had
      crisis (p = 0.049). There was no evidence of crisis within 30 days after
      thymectomy in group 1 and 5 (15.6%) patients in group 2 (p = 0.0724). There was
      no postoperative death among patients in group 1. Responses to thymectomy in
      group 1 improved significantly, the improvement and pharmacologic remission rate
      had increased up to 100% and 79% at 5-7 years after operation, while the
      improvement and pharmacologic remission rate of group 2 had increased to 81.3% (p
      = 0.0466 vs. group 1) and 50.0% at that time (p = 0.0427 vs. group 1).
      CONCLUSIONS: The present study demonstrated that preoperative plasmapheresis may
      facilitate improved outcomes of patients with myasthenia gravis after thymectomy.

PMID- 15724497
TI  - Beneficial effect of acute normovolemic hemodilution in cardiovascular surgery.
AB  - OBJECTIVE: The efficacy of acute normovolemic hemodilution (ANH) in avoiding
      homologous blood transfusion (HBT) during cardiovascular surgery remains
      controversial. Our objective was to evaluate the impact of ANH on blood
      transfusion requirements during open cardiovascular surgery using cardiopulmonary
      bypass (CPB). METHODS: We retrospectively reviewed 243 patients who had undergone
      open cardiac or thoracic aortic surgery using CPB between September 2001 and July
      2003 in our department. ANH was performed when the hematocrit was over 35% and
      the patient was hemodynamically stable. Risk factors were selected in accordance
      with the Japanese Adult Cardiovascular Surgery Database and analyzed to determine
      their effect on perioperative HBT requirement. RESULTS: Of the 243 patients, 64
      (26%) underwent preoperative autologous blood donation and 62 (26%) ANH. HBT was
      required in 62% of patients (150/243) overall, in 32% (20/62) of ANH patients,
      and in 76% (130/171) of non-ANH patients. Multivariate stepwise logistic
      regression analysis revealed that preoperative or pre-donation hemoglobin value
      (p < 0.001), duration of surgery (p = 0.001), intraoperative minimum rectal
      temperature (p = 0.001), age (p = 0.002), need for emergency surgery (p = 0.003),
      amount of ANH (p = 0.018), blood loss (p = 0.033) and amount of preoperative
      autologous blood donation (p = 0.042) were independent predictors of the need for
      perioperative HBT. CONCLUSIONS: Our data showed that open cardiovascular surgery
      using CPB continues to pose a high risk of HBT, but that ANH is an effective
      means of reducing this risk in those patients undergoing these operations.

PMID- 15724496
TI  - Oral cibenzoline reduces postoperative atrial fibrillation in coronary artery
      bypass grafting.
AB  - OBJECTIVE: The objective of the present study was to investigate the
      effectiveness of postoperative oral administration of cibenzoline for the
      prevention of atrial fibrillation (AF) in coronary artery bypass grafting (CABG).
      METHODS: A total of 39 patients who underwent isolated CABG from September 2000
      to February 2001 and who took oral cibenzoline (300 mg per day for 10 days
      beginning immediately after surgery) were compared to 59 patients who underwent
      surgery in our department 8 months prior to the study and who did not take
      cibenzoline for incidence of postoperative AF. Exclusion criteria encompassed age
      (>80 years), low ejection fraction (<30%), high serum creatinine level (>2.0
      mg/dL), and history of supraventricular arrhythmia with or without treatment by
      anti-arrhythmic drugs. RESULTS: Postoperative AF occurred in 2 patients in the
      cibenzoline group (2/35, 5.7%) and 20 patients in the control group (20/59,
      33.9%). There were significant differences in the incidence of postoperative AF
      (p = 0.002). Multivariate analysis revealed that the administration of
      cibenzoline reduced the incidence of AF significantly, and that a large number of
      bypass grafts significantly contributed to postoperative AF in CABG. The number
      of bypass grafts was significantly larger in the cibenzoline group, indicating
      that cibenzoline administration significantly suppresses the incidence of AF
      after CABG in high-risk patients. CONCLUSIONS: Postoperative administration of
      oral cibenzoline for 10 days is one effective method for the prevention of AF
      after CABG.

PMID- 15724498
TI  - Pulmonary nodules 10 mm or less in diameter with ground-glass opacity component
      detected by high-resolution computed tomography have a high possibility of
      malignancy.
AB  - OBJECTIVES: For the histological diagnosis of small lung cancers of 10 mm or less
      in diameter (< or =10), resection by video-assisted thoracic surgery (VATS) with
      computed tomography (CT)-guided marking is feasible. One problem is that a small
      number of these pulmonary nodules are malignant. We retrospectively analyzed CT
      images of pulmonary nodules to find better criteria to select candidates for
      resection among patients with small pulmonary nodules. METHODS: Ninety-four
      patients with indeterminate peripheral pulmonary nodules underwent wedge
      resection by VATS. High-resolution CT using a 1.25 mm slice included the area of
      lesions. Nodules were classified by size (< or =10, 11 to 20, >20 mm) and whether
      they had a ground-glass opacity (GGO) component. RESULTS: The histology of all 94
      nodules showed 52 primary lung cancers, 6 metastatic tumors, 5 benign tumors, 8
      intrapulmonary lymph nodes, and 23 inflammatory nodules. Ninety-three percent of
      nodules larger than 20 mm, 75% of nodules 10 to 20 mm, and 43% of nodules < or
      =10 mm were malignant. Introducing a classification according to GGO component to
      nodules, malignancy was detected in 88% of nodules with a GGO component and in
      30% of nodules without a GGO component among nodules < or =10 mm. Nodules < or
      =10 mm with a GGO component showed a statistically significant (p < 0.01)
      correlation with malignancy. CONCLUSIONS: Pulmonary nodules < or =10 mm with GGO
      should be considered to have a high possibility of malignancy and to be
      candidates for resection by VATS.

PMID- 15724499
TI  - Intentional limited resection for small peripheral lung cancer based on
      intraoperative pathologic exploration.
AB  - OBJECTIVE: The aim of this study was to assess the adequacy of our intentional
      limited resection for small peripheral lung cancer based on intraoperative
      pathologic exploration. METHODS: Patients who had stage IA non-small cell lung
      cancer (NSCLC) with a maximum tumor diameter of 2 cm or less were candidates for
      limited resection. If bronchioloalveolar carcinoma (BAC) was suspected on
      computed tomography and intraoperative pathologic exploration revealed the lesion
      as BAC without foci of active fibroblastic proliferation (Noguchi type A and B),
      wedge resection was performed. If the tumor was not suspected of being Noguchi
      type A or B, extended segmentectomy with intraoperative lymph node exploration
      was performed. RESULTS: Limited resection was performed in 34 patients, wedge
      resection in 14, and extended segmentectomy in 20. The median follow-up period
      after wedge resection was 36 months, and all patients are alive with no signs of
      recurrence. The median follow-up period after extended segmentectomy was 54
      months. No local recurrences were found, but distant metastasis was diagnosed in
      one patient. The 5-year survival rate after extended segmentectomy was 93%. In
      the same period, lobectomy was performed in 57 patients with stage IA NSCLC with
      a maximum tumor diameter of 2 cm or less, and the 5-year survival rate was 84%.
      There were no significant differences in 5-year survival between extended
      segmentectomy and lobectomy. CONCLUSIONS: Careful selection of patients based on
      high-resolution computed tomography findings and intraoperative pathologic
      exploration makes intentional limited resection an acceptable option for the
      treatment of small peripheral NSCLC.

PMID- 15724500
TI  - Does antiphospholipid antibody syndrome affect bioprosthetic heart valve? Midterm
      echocardiographic report.
AB  - Cardiovascular involvements in antiphospholipid antibody syndrome have been
      recognized as a major complication of this disease. Furthermore, some papers
      report bioprosthetic heart valve also seems to be affected. A 32-year-old female
      with aortic regurgitation presented to our hospital. Further examination revealed
      high titer of anticardiolipin beta 2 glycoprotein 1 antibody, and she was
      diagnosed as having primary antiphospholipid antibody syndrome since the patient
      failed to match the criteria of systemic lupus erythematosus. Cardiopulmonary
      bypass was uneventfully conducted under systemic heparinization of usual dosage.
      Administration of warfarin sodium was started on the third postoperative day, and
      international normalized ratio was controlled from 2.0 to 2.5. On
      echocardiographic examination at 1 month, mean systolic gradient was 17 mmHg.
      Although transesophageal echocardiography at 2 years after surgery revealed no
      sign of valvular destruction or sclerosis, transaortic gradient had increased to
      26 mmHg. Bioprosthetic stenosis was suspected probably due to pannus formation
      and the patient may have to undergo another valve replacement in the near future.

PMID- 15724501
TI  - Late-onset chylothorax after pulmonary resection and systematic mediastinal lymph
      node dissection for lung cancer.
AB  - Late-onset chylothorax occurred 49 days after right lower lobectomy for lung
      cancer in a 76-year-old man. Chylothorax was successfully managed by conservative
      treatment with chest tube drainage and an enteral low-fat diet. Chylothorax may
      occur in the late period after pulmonary resection and systematic mediastinal
      lymph node dissection for lung cancer, for which conservative management is the
      treatment of choice.

PMID- 15724502
TI  - Surgical treatment for coronary artery aneurysm.
AB  - Two successful cases of the surgical treatment for coronary artery aneurysm (non
      Kawasaki disease) were reported. The first case had a saccular aneurysm on the
      left circumflex coronary artery (LCx) #14. Resection of the LCx aneurysm was
      performed subsequent to single vessel coronary artery bypass grafting (CABG) to
      the distal portion of LCx#14 under the cardioplegic cardiac arrest. The second
      case had aneurysms on both the left anterior descending artery (LAD) #7
      (fusiform) and the LCx#11 (saccular). After double vessel CABG to LAD#7 and
      LCx#11, ligation or resection of two aneurysms was performed successfully.
      Postoperative courses have been uneventful with good angiographic results
      achieved. Since these surgical procedures demonstrated safety, the patients are
      expected to achieve a good long-term prognosis.

PMID- 15724503
TI  - Persistent left superior vena cava draining to left atrium with normal coronary
      sinus.
AB  - In embryology, a persistent connection of the left superior vena cava to the left
      atrium rarely coexists with a coronary sinus. We herein report an unusual case of
      persistent left superior vena cava terminating in a left atrium with normal
      coronary sinus, which was revealed at the time of permanent pacemaker
      implantation after a second operation for recurrent left atrioventricular valve
      regurgitation. Because this anomaly had gone undiagnosed at the first operation,
      we were unable to diagnose it prior to the second operation, because the
      preoperative coronary angiogram clearly demonstrated a coronary sinus that was
      not dilated. We would have repaired the anomaly using a patch or other procedure
      had it been diagnosed before the second operation in order to prevent cyanosis or
      brain complications secondary to right-to-left shunting. One should always be on
      guard for this rare condition.

PMID- 15724504
TI  - Off-pump coronary artery bypass combined with abdominal aortic aneurysm repair in
      an 88-year-old male.
AB  - We present the case of an 88-year-old patient who underwent off-pump coronary
      artery bypass using an aortic connector followed by repair of an abdominal aortic
      aneurysm to reduce surgical invasiveness. This approach merits consideration for
      high-risk patients.

PMID- 15724505
TI  - Free-floating left atrial ball thrombus without mitral valve disease.
AB  - Reports of left atrial ball thrombus without mitral valve disease are few. We
      experienced a case of free-floating left atrial ball thrombus that developed in a
      short period in a patient with atrial fibrillation and dilated left atrium but
      intact mitral valve. Surgical removal of the thrombus was performed. It was
      presumed that atrial fibrillation and enlarged left atrium were the contributory
      factors to thrombus development.

PMID- 15724506
TI  - Thyroid cancer with massive invasion into the neck and mediastinal great veins.
AB  - Papillary thyroid carcinoma with massive invasion into the great veins of the
      neck and mediastinum has rarely been reported and is thought to have a poor
      prognosis. Here we report successful management of a case of papillary thyroid
      carcinoma with extensive invasion into the left internal jugular vein, left
      brachiocephalic vein, and superior vena cava, followed by reconstruction of the
      superior vena cava using an artificial graft. The operation was conducted to
      prevent sudden death due to complete obstruction of venous flow, improve the
      patient's quality of life, and prolong survival. The patient has survived for
      more than two years after surgery, with good general condition.

PMID- 15724507
TI  - Endovascular surgery using an original occluder for patent ductus arteriosus in
      an adult patient.
AB  - The patient was a 67-year-old woman in whom patent ductus arteriosus was
      diagnosed in childhood but not treated. In April 2000, she was hospitalized for
      exacerbation of heart failure. Marked restrictive impairment was seen: %VC was
      36.1%, and FEV1% was 77.0% (respiratory function tests). As calcification was
      present, and since the aortic opening measured 20 mm, coil occlusion or
      thoracoscopic surgical interruption were considered difficult to perform. Because
      of concerns about postoperative respiratory complications associated with
      thoracotomy, the ductus was occluded under local anesthesia using an original
      occluder consisting of a vascular graft and modified Z-stent. Postoperatively,
      during more than three years of follow-up, the patient has remained well with no
      residual shunt or occluder migration. Consequently, patent ductus arteriosus
      occlusion using an original occluder appears to be a superior, minimally invasive
      technique that can successfully treat large ductus arteriosus complicated by
      calcification.

PMID- 15724508
TI  - [Psychological changes during rehabilitation for newly visually impaired people].
AB  - In study 1, the purpose was to examine the psychological changes during
      rehabilitation for newly visually impaired people. Before and after the 6 months
      rehabilitation training, we conducted Yatabe-Guilford Personality Inventory and
      Manifest Anxiety Scale (MAS). The results showed that scores of depression,
      cyclic tendencies, feeling of inferiority, nervousness, lack of objectivity, and
      anxiety decreased and ascendance increased significantly. In study 2, we compared
      the differeces of scores between those who needed psychotherapy in addition to
      rehabilitation training and those who didn't. People who needed psychotherapy
      scored significantly higher on the depression and lack of objectivity scales than
      those who didn't. Supportive and behavioral counseling was conducted, however no
      significant changes were observed before and after psychotherapy as a whole.
      Furthermore, the relations among the methods, purposes and effects of
      psychotherapy were not observal. As a conclusion, we need to develop methods of
      psychotherapy which accelerate the acceptance of disability and improve
      psychological adaptation sufficiently.

PMID- 15724509
TI  - [The influence of the member's life in "destructive cults" on the psychological
      problems after departing from the groups].
AB  - The purpose of this study was to examine the influence of the member's life in
      destructive cults on the psychological problems after departing from the groups.
      A factor analysis was performed with the data of questionnaires toward 157
      participants, and seven factors were extracted. They were (1) avoidance behavior
      to avoid out-groups, (2) restriction of freedom, (3) satisfaction, (4) behavior
      of submission, (5) compliance with rules, (6) punishment and reward, and (7)
      mysterious experience. Analyses of variance showed that restriction of freedom
      and punishment and reward are more likely to develop personal distress, whereas
      mysterious experiences are more likely to develop personal distress and
      interpersonal distress.

PMID- 15724510
TI  - [A study on the structure of the intention to become ideal selves: from the
      viewpoint of the relationship to subjective ratings of ideal selves ].
AB  - This study examined the structure of the "intention to become ideal selves", the
      autonomous direct approaches in building into an ideal self. Only when people
      feel meanings or worth on an ideal self, do people have the intention to be it.
      It was predicted that if people feel meanings or worth on ideal selves, some
      affect related to it would rise. In addition, we predicted that the possibility
      to actualize ideal selves would directly or indirectly promote the intention to
      become ideal selves. A structural model based on these hypotheses was examined,
      controlling for sex and contents of ideal selves. The questionnaire was
      administered during class to 1 052 university students (F = 453, M = 599). The
      hypothetical structural model was examined by SEM and yielded a good estimate of
      model fit, and fully estimated the intention to become ideal selves. Although
      this structural model showed good estimates of model fit regardless of sex or
      contents of ideal selves, there were some differences in the standardized
      coefficient of the possibility to actualize ideal selves depending on the
      contents of ideal selves.

PMID- 15724511
TI  - [Anisotropy in depth perception of photograph].
AB  - How can we reproduce real physical depth from a photograph? How does depth
      perception in the photograph differ from depth perception in the direct
      observation? In Experiment 1, objects in an open space were photographed and
      presented on a screen. Subjects were asked to judge the distances from a fixed
      point to the objects and the angles from the median line. The distances and the
      angles in the photograph were perceived shorter and larger than in physical
      space, respectively. Furthermore, depth perception in the photograph had an
      anisotropic property. In Experiment 2, the same objects as in Experiment 1 were
      observed directly by the subjects. The distances and the angles in the direct
      observation were perceived longer and smaller at longer distance than in the
      photograph, respectively. It was concluded that depth perception in the
      photograph did not reproduce depth either in physical space or in visual space,
      but it was closer to depth in visual space than in physical space. Furthermore,
      photographic space had an anisotropic property as visual space did.

PMID- 15724512
TI  - [Analysis of paired comparison data based on experimental design: expression
      using structural equation modeling].
AB  - Paired comparison is a useful method for assessing ranks among several objects,
      and it enables us to obtain more reliable data than assessing objects one by one.
      But paired comparison principally provides information only about the ranks of
      the objects. On the other hand, experimental design provides a framework for
      elucidating causal associations. If we could analyze paired comparison data by
      the experimental design framework, it would be a very effective method. But
      experimental design, in its original form, is not readily applicable to paired
      comparison data. However, if we adopt the perspective of structural equation
      modeling (SEM), we can deal with paired comparison and experimental design in a
      unified way, because they are both submodels of SEM. The purpose of this study is
      to provide a new method to analyze causal connection of paired comparison data by
      using SEM. Here, two actual numerical examples are shown, one of which is
      obtained by within-subject design and the other is obtained by between-subject
      design.

PMID- 15724513
TI  - [The effect of target degradation on detection of semantic satiation in a lexical
      decision task].
AB  - In this study, it was examined whether or not visual quality of letter strings
      influenced the detection of semantic satiation in a lexical decision task.
      Previous studies concluded that lexical decision tasks cannot detect semantic
      satiation, because semantic information was not fully utilized in this task.
      Recently, however, it has been shown that semantic satiation is detected in this
      task as long as semantic information of the target was fully utilized. This study
      examined whether or not semantic satiation in the lexical decision task is found
      when a visually degraded target was presented. Forty-eight college students
      participated in the experiment. Semantic satiation was found in the degraded
      target condition, but not found in the intact target condition, which was
      consistent with the previous studies. These results suggest that this effect in
      the lexical decision task is found only if the target is degraded, and semantic
      information of the target is available for the decision.

PMID- 15724514
TI  - [Adjustment to spousal bereavement and successful aging: a 16-year longitudinal
      study].
AB  - The objective of this study was to prove the hypothesis that successful aging was
      predicted by the recovery processes during the first few years of bereavement.
      The subjects were 184 elderly persons, whose spouses died three to 14 months
      prior to the first survey. Interviews were held three times in 16 years. Results
      showed that the depression level at the first interview was a significant factor
      to predict the sickness and death at the second interview, but not at the third
      interview. When the level of loneliness increased by the second interview than at
      the first, it was revealed that there were risks in sickness and death for the
      third interview. If the level of loneliness increased or remained high after
      bereavement, mental health conditions during the third interview tended to be
      poor. On the other hand, as loneliness decreased, happiness during the third
      interview increased. We concluded that a change in loneliness after bereavement
      was the key factor in suggesting the process of successful aging.

PMID- 15724515
TI  - [Relationship between the effects of word emotionality and the consciousness of
      retrieval process in memory].
AB  - Two experiments were carried out to examine the effects of word emotionality on
      explicit and implicit memory. In Experiment 1, 46 undergraduates studied a word
      list followed by free recall or word-stem completion test. The list was consisted
      of 36 nouns with pleasant, neutral, and unpleasant words. In free recall test,
      both the pleasant and unpleasant words were more recalled than the neutral words.
      In word-stem completion test, there were no significant effects of emotional
      value. Experiment 2 reexamined the result of word-stem completion test in
      Experiment 1. A process-dissociation procedure was used to estimate two
      components of conscious and automatic retrieval process in implicit memory. The
      results suggest that the emotionality of words had a facilitative effect on
      conscious component but no effect on unconscious component.

PMID- 15724516
TI  - [The effect of encoding on false memory: examination on levels of processing and
      list presentation format].
AB  - Using the Deese/Roediger-McDermott paradigm, the effects of lists presentation
      format (blocked/random) and levels of processing of critical nonpresented lures
      were examined. A levels-of-processing effect in a blocked presentation order was
      not observed for lures. Rates of false recognition and remember judgments for
      lures in a shallow level of processing were significantly lower than those in a
      deep level of processing when items from various themes were inter-mixed instead
      of blocked. Results showed an interaction between levels of processing and list
      presentation format. It is thus concluded that encoding of each word and whole
      list should be both considered in understanding false memory.

PMID- 15724517
TI  - [Determinant factors of community-based disaster preparedness: a case study of
      flood prone area].
AB  - This study examined the determinants of willingness to participate in a community
      based disaster preparedness scheme. The theory of reasoned action (Ajzen &
      Fishbein, 1977, 1980; Fishbein & Ajzen, 1975) was applied as a basic model and
      was complemented by the factor of concern about disaster. A structural equation
      modeling was performed to validate this model. The hypothetical model was
      supported for the data from the residents (N = 3 036) of an area with a high risk
      of flood damage. It was clarified that the subjective norm and concern about
      flood positively contributed to the intention of participating in a community
      based disaster preparedness scheme. The perceived cost of preparedness was the
      inhibitory factor of participating in such a scheme.

PMID- 15724518
TI  - [The Autism-Spectrum Quotient (AQ) Japanese version: evidence from high
      functioning clinical group and normal adults].
AB  - Baron-Cohen, Wheelwright, Skinner, Martin, and Clubley (2001) constructed brief,
      self-administered instruments named the Autism-Spectrum Quotient (AQ), for
      measuring the degree to which an adult with normal intelligence has the traits
      associated with the autistic spectrum. In this paper, we report on a Japanese
      version of this new instrument. Three groups of Japanese subjects were assessed.
      Group 1 (n = 57) consisted of adults with Asperger Syndrome (AS) or high
      functioning autism (HFA). The other two groups were control groups. Subjects of
      Group 2 (n = 194) were normal adults and those of Group 3 (n = 1 050) were
      students selected from five Universities in Tokyo and Chiba. The adults with
      AS/HFA had a mean AQ score of 37.9 (SD = 5.31), which was significantly higher
      than the two control groups (Group 2: X = 18.5, SD = 6.21, and Group 3: X = 20.7,
      SD = 6.38). While eighty-eight percent of the adults with AS/HFA scored more than
      33 points, only 3% of subjects in the two control groups indicated those points.
      Among the controls, males scored slightly but significantly higher than females.
      The reliability of the AQ in both test-retest and inter-rater measures were
      significantly high.

PMID- 15724519
TI  - Self-reported outcome in new hearing aid users over a 24-week post-fitting
      period.
AB  - Evidence for the existence of auditory acclimatization is mixed, and the
      implications for clinical practice are unclear. The aim of this study was to seek
      evidence of perceived changes in performance over a 24-week post-fitting period.
      Thirty-two new, elderly subjects were recruited and fitted monaurally with the
      same model of linear, programmable hearing aid that provided in excess of 20-dB
      insertion gain at 2000-4000 Hz. The Glasgow Hearing Aid Benefit Profile (GHABP)
      was used to measure self-reported changes over time. The questions concerning
      benefit and satisfaction were modified to produce two versions: half of the
      subjects reported changes relative to the time of fitting, while the remainder
      reported changes relative to the previous occasion on which they completed the
      GHABP (3 weeks earlier). Subjects reported using hearing aids in excess of 90% of
      the time when in listening situations that cause difficulty. The median residual
      disability measure from the GHABP remained low (10-20%) over the duration of the
      study. The median scores for additional benefit and satisfaction showed a small
      but statistically significant improvement over the first 3 months of hearing aid
      use but only for the subjects who referenced this to their perceived performance
      3 weeks earlier. The limited evidence for self-reported improvements in benefit
      and satisfaction over time reported to date must be tempered by the possibility
      of response bias arising from the method used to measure changes over time.

PMID- 15724520
TI  - Self-reported outcomes of aural rehabilitation in a developing country.
AB  - The aim of this study was to evaluate self-reported outcomes among hearing aid
      users (age 16-89 years; mean 45.8 years) to determine the effectiveness of aural
      rehabilitation in Nigeria based on the International Outcome Inventory for
      Hearing Aids (IOI-HA). The responses were evaluated with descriptive statistics,
      factor analysis of the principal components and multiple regressions. Most
      respondents reported favorable outcomes in all domains of the inventory,
      comprising: daily use (mean 4.1; SD 1.2), benefits (mean 3.5; SD 1.1), residual
      activity limitation (mean 3.4; SD 1.2), satisfaction (mean 3.7; SD 1.2), residual
      participation restriction (mean 3.5; SD 1.3), impact on others (mean 3.4; SD 1.3)
      and changes in quality of life (mean 3.8; SD 1.0). The mean score distribution
      compared favorably with those reported in the developed world. There were
      significant intercorrelations among all items, and two factors (eigenvalue>1)
      accounted for 68% of the underlying variance. Impact on others was the only
      domain associated with demographic/audiologic variables. The study showed that
      aural rehabilitation is feasible and effective in enhancing activity and
      participation for the hearing impaired in a developing country.

PMID- 15724521
TI  - Social hearing measured with the Performance Inventory for Profound and Severe
      Loss: a comparison between adult multichannel cochlear implant patients and users
      of acoustical hearing aids.
AB  - The objective of this study was to investigate social hearing in successful users
      of multichannel cochlear implants (CIs) and to compare the scores with those of a
      group of hearing-impaired adults using acoustical hearing aids (HAs). Out of 88
      patients who had undergone surgery, 75 CI users with a mean age of 55 years and a
      mean pre-operative hearing level of 113dB in the better ear were compared with 59
      users of acoustical HAs with a mean age of 56 years and a mean hearing level of
      82dB in the better ear. Seven CI patients were non-users and were excluded from
      the study. The Performance Inventory for Profound and Severe Loss, a
      questionnaire that measures different aspects of hearing handicap, was used. The
      CI group scored significantly better than the HA group in three of six evaluated
      categories, measuring subjective intensity of sounds, speech with visual cues,
      and response to auditory failure. Awareness of environmental sounds, speech with
      no visual cues and personal reactions did not differ significantly. The group of
      successful CI users scored higher on a self-report measure than did a group of
      users of acoustical HAs with moderate- severe-profound deafness. The best CI
      users scored better than the best HA users, and the worst CI users scored worse
      than the worst HA users.

PMID- 15724522
TI  - Handling of the MED-EL TEMPO+ ear-level speech processor by paediatric cochlear
      implant users and their parents.
AB  - MED-EL launched the first ear-level speech processor offering a high-rate CIS+
      strategy, the TEMPO+, in 1999. Studies have already demonstrated improved speech
      perception, sound quality and ability to enjoy music with the TEMPO+ due to the
      new CIS+ speech-coding strategy, when compared to the body-worn processor. In
      this study we evaluated responses from parents of young children about ease of
      handling and usage of the TEMPO+, and satisfaction with the TEMPO+ and its
      performance. Overall, 65 custom-designed questionnaires were analysed. The
      results showed that MED-EL cochlear implant users felt comfortable manipulating
      the dials and switches, changing the battery pack, using external sources of
      input and using the accessories provided. These results confirm the suitability
      of the TEMPO+ for infants and toddlers.

PMID- 15724523
TI  - Beliefs and attitudes among Swedish workers regarding the risk of hearing loss.
AB  - The beliefs and attitudes regarding the risk of hearing loss and their impact on
      hearing protector use were investigated among Swedish workers. A questionnaire,
      developed by the US National Institute for Occupational Safety and Health
      (NIOSH), was used. The study objective was to assess workers' attitudes towards
      using hearing protection devices (HPDs) and to enhance the ability of workers to
      protect themselves from occupational hearing loss. Ninety-five per cent of the
      respondents were aware that loud noise could damage their hearing, 90% considered
      that a hearing loss would be a serious problem, and 85% believed that HPDs could
      protect their hearing. However, lower percentages of workers always used the HPDs
      when they were noise-exposed. Fifty-five per cent of the workers indicated that
      they could not hear warning signals when using HPDs, and 45% of the workers
      indicated that they considered HPDs to be uncomfortable. These issues must be
      addressed to make HPD use more effective.

PMID- 15724524
TI  - Disturbance caused by varying propagation delay in non-occluding hearing aid
      fittings.
AB  - The disturbance caused by various short propagation delays to the perception of
      external sounds and own voice for a non-occluding hearing aid was investigated.
      Ten normal-hearing and 10 mildly hearing-impaired individuals listened to
      external sounds and their own voice while wearing non-occluding devices providing
      10dB of linear gain. Participants rated the disturbance caused by delays of 2, 4
      and 10ms to music, running speech, and their own voices. The results indicated
      greater disturbance for the longest delay for both subject groups when judging
      own voice, with the ratings of the hearing-impaired participants being lowest.
      Normal-hearing participants also judged the 10-ms delay as more disturbing for
      the external sounds. Owing to the listening conditions with constant gain from
      800Hz and above, the results apply directly only to this experiment. Disturbance
      ratings for all delays were low, which suggests that any of those tested would be
      acceptable for this application.

PMID- 15724525
TI  - Rapid assessment of tinnitus-related psychological distress using the Mini-TQ.
AB  - The aim of this study was to develop an abridged version of the Tinnitus
      Questionnaire (TQ) to be used as a quick tool for the assessment of tinnitus
      related psychological distress. Data from 351 inpatients and 122 outpatients with
      chronic tinnitus were used to analyse item statistics and psychometric
      properties. Twelve items with an optimal combination of high item-total
      correlations, reliability and sensitivity in assessing changes were selected for
      the Mini-TQ. Correlation with the full TQ was >0.90, and test-retest reliability
      was 0.89. Validity was confirmed by associations with general psychological
      symptom patterns. Treatment effects indicated by the Mini-TQ were slightly
      greater than those indicated by the full TQ. The Mini-TQ is recommended as a
      psychometrically approved and solid tool for rapid and economical assessment of
      subjective tinnitus distress.

PMID- 15724526
TI  - Sexually transmitted infections in practice.

PMID- 15724527
TI  - A guide to sexual pain in men.

PMID- 15724528
TI  - Progestogen-only contraception: a review.

PMID- 15724529
TI  - The patient with erectile dysfunction.

PMID- 15724530
TI  - Understanding seasonal affective disorder.

PMID- 15724531
TI  - Preparing for the Multiple Choice Paper.

PMID- 15724532
TI  - X-ray CT high-density artefact suppression in the presence of bones.
AB  - This paper presents a novel method of reducing x-ray CT high-density artefacts
      generated by metal objects when abundant bone structures are present in the
      region of interest. This method has an advantage over previously proposed methods
      since it heavily suppresses the metal artefacts without introducing extra bone
      artefacts. The method of suppression requires that bone pixels are isolated and
      segmented by thresholding. Then artificial CT numbers are assigned to the bone
      pixels so that their projection profiles are smooth and thus can be properly
      simulated by a polynomial interpolation. The projection profile of the metal
      object is then removed to fully suppress the artefacts. The resulting processed
      profile is fed to a reconstruction routine and the previously preserved bone
      pixels added back. The new method utilizes two important features of the CT image
      with metal artefacts: (a) metal and bone pixels are not severely affected by the
      high-density artefacts and (b) the high-density artefacts can be located in
      specific projection channels in the profile domain, although they are spread out
      in the image domain. This suppression method solves the problem of CT image
      artefacts arising from metal objects in the body. It has the potential to greatly
      improve diagnostic CT imaging in the presence of these objects and treatment
      planning that utilizes CT for patients with metal applicators (e.g.,
      brachytherapy for cervix cancer and prostate cryotherapy).

PMID- 15724533
TI  - Performance of coincidence imaging with long-lived positron emitters as an
      alternative to dedicated PET and SPECT.
AB  - An important application of quantitative imaging in nuclear medicine is the
      estimation of absorbed doses in radionuclide therapy. Depending on the
      radionuclide used for therapy, quantitative imaging of the kinetics of the
      therapeutic radiopharmaceutical could be done using planar imaging, SPECT or PET.
      Since many nuclear medicine departments have a gamma camera system that is also
      suitable for coincidence imaging, the performance of these systems with respect
      to quantitative imaging of PET isotopes that could be of use in radionuclide
      dosimetry is of interest. We investigated the performance of a gamma camera with
      coincidence imaging capabilities with 99mTc, 111In, 18F and 76Br and a dedicated
      PET system with 18F and 76Br, using a single standard set of phantom
      measurements. Here, 76Br was taken as a typical example of prompt gamma-emitting
      PET isotopes that are applicable in radionuclide therapy dosimetry such as 86Y
      and 124I. Image quality measurements show comparable image contrasts for 76Br
      coincidence imaging and 111In SPECT. Although the spatial resolution of
      coincidence imaging is better than single photon imaging, the contrast obtained
      with 76Br is not better than that with 99mTc or 111In because of the prompt gamma
      involved. Additional improvements are necessary to allow for quantitative
      coincidence imaging of long-lived, prompt gamma producing positron emitters.

PMID- 15724534
TI  - Normalized glandular dose (DgN) coefficients for flat-panel CT breast imaging.
AB  - The development of new digital mammography techniques such as dual-energy
      imaging, tomosynthesis and CT breast imaging will require investigation of
      optimal camera design parameters and optimal imaging acquisition parameters. In
      optimizing these acquisition protocols and imaging systems it is important to
      have knowledge of the radiation dose to the breast. This study presents a
      methodology for estimating the normalized glandular dose to the uncompressed
      breast using the geometry proposed for flat-panel CT breast imaging. The
      simulation uses the GEANT 3 Monte Carlo code to model x-ray transport and
      absorption within the breast phantom. The Monte Carlo software was validated for
      breast dosimetry by comparing results of the normalized glandular dose (DgN)
      values of the compressed breast to those reported in the literature. The
      normalized glandular dose was then estimated for a range of breast diameters from
      10 cm to 18 cm using an uncompressed breast model with a homogeneous composition
      of adipose and glandular tissue, and for monoenergetic x-rays from 10 keV to 120
      keV. These data were fit providing expressions for the normalized glandular dose.
      Using these expressions for the DgN coefficients and input variables such as the
      diameter, height and composition of the breast phantom, the mean glandular dose
      for any spectra can be estimated. A computer program to provide normalized
      glandular dose values has been made available online. In addition, figures
      displaying energy deposition maps are presented to better understand the spatial
      distribution of dose in CT breast imaging.

PMID- 15724535
TI  - Translational and Brownian motion in laser-Doppler flowmetry of large tissue
      volumes.
AB  - This study reports the derivation of a precise mathematical relationship existing
      between the different p-moments of the power spectrum of the photoelectric
      current, obtained from a laser-Doppler flowmeter (LDF), and the red blood cell
      speed. The main purpose is that both the Brownian (defining the 'biological
      zero') and the translational movements are taken into account, clarifying in this
      way what the exact contribution of each parameter is to the LDF derived signals.
      The derivation of the equations is based on the quasi-elastic scattering theory
      and holds for multiple scattering (i.e. measurements in large tissue volumes
      and/or very high red blood cell concentration). The paper also discusses why
      experimentally there exists a range in which the relationship between the first
      moment of the power spectrum and the average red blood cells speed may be
      considered as 'linear' and what are the physiological determinants that can
      result in nonlinearity. A correct way to subtract the biological zero from the
      LDF data is also proposed. The findings should help in the design of improved LDF
      instruments and in the interpretation of experimental data.

PMID- 15724536
TI  - The dose distribution of low dose rate Cs-137 in intracavitary brachytherapy:
      comparison of Monte Carlo simulation, treatment planning calculation and polymer
      gel measurement.
AB  - In this study, the dose distribution delivered by low dose rate Cs-137
      brachytherapy sources was investigated using Monte Carlo (MC) techniques and
      polymer gel dosimetry. The results obtained were compared with a commercial
      treatment planning system (TPS). The 20 mm and the 30 mm diameter Selectron
      vaginal applicator set (Nucletron) were used for this study. A homogeneous and a
      heterogeneous-with an air cavity-polymer gel phantom was used to measure the dose
      distribution from these sources. The same geometrical set-up was used for the MC
      calculations. Beyond the applicator tip, differences in dose as large as 20% were
      found between the MC and TPS. This is attributed to the presence of stainless
      steel in the applicator and source set, which are not considered by the TPS
      calculations. Beyond the air cavity, differences in dose of around 5% were noted,
      due to the TPS assuming a homogeneous water medium. The polymer gel results were
      in good agreement with the MC calculations for all the cases investigated.

PMID- 15724537
TI  - Treatment simulation approaches for the estimation of the distributions of
      treatment quality parameters generated by geometrical uncertainties.
AB  - Geometric uncertainties arise during treatment planning and treatment and mean
      that dose-dependent parameters such as EUD are random variables with a patient
      specific probability distribution. Treatment planning with highly conformal
      treatment techniques such as intensity modulated radiation therapy requires new
      evaluation tools which allow us to estimate this influence of geometrical
      uncertainties on the probable treatment dose for a planned dose distribution.
      Monte Carlo simulations of treatment courses with recalculation of the dose
      according to the daily geometric errors are a gold standard for such an
      evaluation. Distribution histograms which show the relative frequency of a
      treatment quality parameter in the treatment simulations can be used to evaluate
      the potential risks and chances of a planned dose distribution. As treatment
      simulations with dose recalculation are very time consuming for sufficient
      statistical accuracy, it is proposed to do treatment simulations in the dose
      parameter space where the result is mainly determined by the systematic and
      random component of the geometrical uncertainties. Comparison of the parameter
      space simulation method with the gold standard for prostate cases and a head and
      neck case shows good agreement as long as the number of fractions is high enough
      and the influence of tissue inhomogeneities and surface curvature on the dose is
      small.

PMID- 15724538
TI  - Fan-beam and cone-beam image reconstruction via filtering the backprojection
      image of differentiated projection data.
AB  - In this paper, a new image reconstruction scheme is presented based on Tuy's cone
      beam inversion scheme and its fan-beam counterpart. It is demonstrated that Tuy's
      inversion scheme may be used to derive a new framework for fanbeam and cone-beam
      image reconstruction. In this new framework, images are reconstructed via
      filtering the backprojection image of differentiated projection data. The new
      framework is mathematically exact and is applicable to a general source
      trajectory provided the Tuy data sufficiency condition is satisfied. By choosing
      a piece-wise constant function for one of the components in the factorized
      weighting function, the filtering kernel is one dimensional, viz. the filtering
      process is along a straight line. Thus, the derived image reconstruction
      algorithm is mathematically exact and efficient. In the cone-beam case, the
      derived reconstruction algorithm is applicable to a large class of source
      trajectories where the pi-lines or the generalized pi-lines exist. In addition,
      the new reconstruction scheme survives the super-short scan mode in both the fan
      beam and cone-beam cases provided the data are not transversely truncated.
      Numerical simulations were conducted to validate the new reconstruction scheme
      for the fan-beam case.

PMID- 15724539
TI  - Performance of a block detector PET scanner in imaging non-pure positron emitters
      -modelling and experimental validation with 124I.
AB  - The key performance measures of resolution, count rate, sensitivity and scatter
      fraction are predicted for a dedicated BGO block detector patient PET scanner (GE
      Advance) in 2D mode for imaging with the non-pure positron-emitting radionuclides
      124I, 55Co, 61Cu, 62Cu, 64Cu and 76Br. Model calculations including parameters of
      the scanner, decay characteristics of the radionuclides and measured parameters
      in imaging the pure positron-emitter 18F are used to predict performance
      according to the National Electrical Manufacturers Association (NEMA) NU 2-1994
      criteria. Predictions are tested with measurements made using 124I and show that,
      in comparison with 18F, resolution degrades by 1.2 mm radially and tangentially
      throughout the field-of-view (prediction: 1.2 mm), count-rate performance reduces
      considerably and in close accordance with calculations, sensitivity decreases to
      23.4% of that with 18F (prediction: 22.9%) and measured scatter fraction
      increases from 10.0% to 14.5% (prediction: 14.7%). Model predictions are expected
      to be equally accurate for other radionuclides and may be extended to similar
      scanners. Although performance is worse with 124I than 18F, imaging is not
      precluded in 2D mode. The viability of 124I imaging and performance in a clinical
      context compared with 18F is illustrated with images of a patient with recurrent
      thyroid cancer acquired using both [124I]-sodium iodide and [18F]-2-fluoro-2
      deoxyglucose.

PMID- 15724540
TI  - Poly(vinyl alcohol) cryogel phantoms for use in ultrasound and MR imaging.
AB  - Poly(vinyl alcohol) cryogel, PVA-C, is presented as a tissue-mimicking material,
      suitable for application in magnetic resonance (MR) imaging and ultrasound
      imaging. A 10% by weight poly(vinyl alcohol) in water solution was used to form
      PVA-C, which is solidified through a freeze-thaw process. The number of freeze
      thaw cycles affects the properties of the material. The ultrasound and MR imaging
      characteristics were investigated using cylindrical samples of PVA-C. The speed
      of sound was found to range from 1520 to 1540 m s(-1), and the attenuation
      coefficients were in the range of 0.075-0.28 dB (cm MHz)(-1). T1 and T2
      relaxation values were found to be 718-1034 ms and 108-175 ms, respectively. We
      also present applications of this material in an anthropomorphic brain phantom, a
      multi-volume stenosed vessel phantom and breast biopsy phantoms. Some suggestions
      are made for how best to handle this material in the phantom design and
      development process.

PMID- 15724541
TI  - Numerical modelling of thermal effects in rats due to high-field magnetic
      resonance imaging (0.5-1 GHZ).
AB  - A finite-difference time-domain (FDTD) thermal model has been developed to
      compute the temperature elevation in the Sprague Dawley rat due to
      electromagnetic energy deposition in high-field magnetic resonance imaging (MRI).
      The field strengths examined ranged from 11.75-23.5 T (corresponding to 1H
      resonances of 0.5-1 GHz) and an N-stub birdcage resonator was used to both
      transmit radio-frequency energy and receive the MRI signals. With an in-plane
      resolution of 1.95 mm, the inhomogeneous rat phantom forms a segmented model of
      12 different tissue types, each having its electrical and thermal parameters
      assigned. The steady-state temperature distribution was calculated using a Pennes
      'bioheat' approach. The numerical algorithm used to calculate the induced
      temperature distribution has been successfully validated against analytical
      solutions in the form of simplified spherical models with electrical and thermal
      properties of rat muscle. As well as assisting with the design of MRI experiments
      and apparatus, the numerical procedures developed in this study could help in
      future research and design of tumour-treating hyperthermia applicators to be used
      on rats in vivo.

PMID- 15724542
TI  - Calibration of Kodak EDR2 film for patient skin dose assessment in cardiac
      catheterization procedures.
AB  - Kodak EDR2 film has been calibrated across the range of exposure conditions
      encountered in our cardiac catheterization laboratory. Its dose-response function
      has been successfully modelled, up to the saturation point of 1 Gy. The most
      important factor affecting film sensitivity is the use of beam filtration.
      Spectral filtration and kVp together account for a variation in dose per optical
      density of -10% to +25%, at 160 mGy. The use of a dynamic wedge filter may cause
      doses to be underestimated by up to 6%. The film is relatively insensitive to
      variations in batch, field size, exposure rate, time to processing and day-to-day
      fluctuations in processor performance. Overall uncertainty in the calibration is
      estimated to be -20% to +40%, at 160 mGy. However, the uncertainty increases at
      higher doses, as the curve saturates. Artefacts were seen on a number of films,
      due to faults in the light-proofing of the film packets.

PMID- 15724543
TI  - Monte Carlo evaluation of kerma in an HDR brachytherapy bunker.
AB  - In recent years, the use of high dose rate (HDR) after-loader machines has
      greatly increased due to the shift from traditional Cs-137/Ir-192 low dose rate
      (LDR) to HDR brachytherapy. The method used to calculate the required concrete
      and, where appropriate, lead shielding in the door is based on analytical methods
      provided by documents published by the ICRP, the IAEA and the NCRP. The purpose
      of this study is to perform a more realistic kerma evaluation at the entrance
      maze door of an HDR bunker using the Monte Carlo code GEANT4. The Monte Carlo
      results were validated experimentally. The spectrum at the maze entrance door,
      obtained with Monte Carlo, has an average energy of about 110 keV, maintaining a
      similar value along the length of the maze. The comparison of results from the
      aforementioned values with the Monte Carlo ones shows that results obtained using
      the albedo coefficient from the ICRP document more closely match those given by
      the Monte Carlo method, although the maximum value given by MC calculations is
      30% greater.

PMID- 15724544
TI  - [Academician N. N. Burdenko and the Moscow school of Neurosurgeons].

PMID- 15724545
TI  - [Skull base meningiomas spreading into the infratemporal fossa: clinical picture,
      diagnosis, and treatment policy].
AB  - From 1997 to 2004, the Academician N. N. Burdenko Research Institute of
      Neurosurgery has operated on 54 patients with intracranial meningiomas spreading
      into the infratemporal fossa. Fifteen patients were operated on for the first
      time. Thirty-nine patients had undergone surgical interventions on the average 3
      times (from 2 to 8). All the patients were operated on via different
      orbitozygomatic approaches depending on the extent of the process. Opening the
      upper and lower palpebral fissures and the round foramen with resection, if
      required, the pterygoid processes suffice to remove tumors from the areas of the
      upper and lower palpebral fissures, which spread into the sphenoid and maxillary
      sinuses. If there are tumors at the site of the base of the anterior surface of
      the pyramid, and the articular bursa, it is expedient to open the oval and
      spinous foramens, to resect the external portions of the fundus of the middle
      cranial fossa and, if required, the articular process of the lower jaw. By taking
      into account the X-ray and histological patterns, it may be stated that invasion
      of meningiomas is not always accompanied by the development of hyperostosis.
      According to our findings, extracranial growth of meningiomas points to the
      invasion of osseous structures of the middle cranial fossa. Furthermore, if
      meningiomas grow into the infratemporal fossa, they frequently involve the
      muscles, nerves, and mucosa. After removing the tumors spreading to the
      infratemporal fossa, the optimum plastic repairs of defects of the base of the
      skull are as follows: hermetic closure of basal defect of the dura mater with a
      free fat flap, by fixing it with sutures and fibrin-thrombin glue with additional
      plastic repair of skull base defect with local displaced tissues on a pedicle
      (with a temporal muscular fascioperiosteal flap, a Bisch fat flap). Further
      policy of management of these patients is a complicated problem. It depends on
      the radicalism of an operation and the invasiveness of the process. The
      histobiological features of infiltrative meningiomas should be studied and this
      will determine management policy. Conceivably, the use of postoperative radiation
      therapy will be substantiated in a definite group of patients.

PMID- 15724546
TI  - [Non-acoustic parastemal schwannomas: results of treatment].
AB  - The paper presents the results of treatment in 15 cases with non-acoustic
      parastemal schwannomas, which amounts to 4.3% in this histological subgroup.
      Among them, there were 7 (2.0%) patients with trigeminal tumors, 5 (1.4%) with
      facial nerve schwannomas, 3 (0.9%) with schwannomas, which were localized in the
      jugular foramen. In 4 (57.1%) cases, trigeminal schwannomas were localized in the
      posterior fossa and in (3.42.9) cases, they spread into the infra- and
      supratentorial areas. Tumors of the jugular foramen spread extracranially in 2
      (66.7%). Their diagnosis was based on clinical intrascopic (computed tomographic
      and magnetic resonance imaging) data. All the cases had sings of acousticofacial
      disorders. For tumor removal, the suboccipital retrosygmoid approach was used in
      12 cases and combined approaches were applied in 3 cases, including 2 (13.3%)
      patients in whom schwannomas were removed via two- or three-stage interventions.
      The anatomic integrity of the cranial nerves adjacent to a tumor was preserved in
      all the cases. After surgery, their mild or moderate dysfunction that did not
      lower life quality was observed in most cases. Liquorea and meningitis were seen
      in 1 (6.7%) case after removal of an extracranial component of trigeminal
      schwannoma. Radical tumor resection was made in 93.3% of cases. Tumor recurrence
      was observed in 1 (6.7%) case. There were no fatal cases in a group of the
      patients operated on. Larger tumors that induce severe deformation of the brain
      stem should be removed in two steps; this makes it possible to rule out their
      rapid redislocation that deteriorates the course of an early postoperative
      period.

PMID- 15724547
TI  - [Complications and failures of endoscopic ventriculostomy of the third
      ventricle].
AB  - The study was undertaken to elucidate the poor outcomes of endoscopic
      ventriculostomy of the third ventricle (EVTV), including complications and
      dysfunctions. A series of 249 consecutive EVTV (the mean age of 15 years in 247
      patients) made at the Institute of Neurosurgery in 1995 to 2003 was analyzed. The
      causes of hydrocephalus were benign tumors in 95 (38%) patients, stenosis of the
      aqueduct of the cerebrum in 73 (29%), malignant tumors in 63 (25%), and other
      causes in 18 (7%) cases. Obstruction in the posterior cranial fossa was present
      in 12 (5%); prior to EVTV, 24 (10%) and 36 (15%) patients had undergone
      craniotomy and bypass surgery, respectively; 12 (5%) patients had sustained
      subarachnoidal or intraventricular hemorrhage, 21 (8%) had intracranial
      infections. The follow-up averaged 16 months. Its results showed that 40
      complications occurred in 34 (14%) patients. Seven (3%) patients required
      unplanned operations; transient and persistent neurological deficits were present
      in 15 (6%) and 2 (1%), respectively; there were no surgery-related deaths.
      Meningitis occurred in 14 (6%) cases; its risk was higher in patients having a
      history of intracranial infections (p = 0.02); meningitis was absent in patients
      with benign tumors (p < 0.01). Intracranial hemorrhages occurred in 7 (3%) cases;
      2 of them required surgical treatment. Moreover, there were 6 (2%) wound
      complications (4 cases of wound cerebrospinal fluid discharge); 5 (2%) EVTVs were
      prematurely discontinued; isolated neurological deficit occurred in 6 (2%),
      single seizures were observed in 2 (1%). There were early dysfunctions in 16 (6%)
      cases; their risk was associated with obstruction in the posterior cranial fossa
      (p = 0.04) and with the technical result of an operation (p < 0.01). Late
      dysfunctions occurred in 21 (8%) cases, on the average, after 12 months of EVTV;
      their risk was higher in patients with malignant tumors (p = 0.04). It is
      concluded that indications for EVTV should be substantiated by the good chance of
      having a steady-state surgical success, by an overall prognosis, and staffs
      experience. The history of intracranial infections requires careful preoperative
      studies. Obstruction at the level of the posterior intracranial fossa is a
      relative contraindication to EVTV due to a low chance of having a success. The
      high risk for late dysfunctions in patients with malignant tumors requires a more
      strict choice of indications in this group. If there is anastomotic dysfunction,
      EVTV may be a good alternative to shunt revision.

PMID- 15724548
TI  - [Percutaneous lumbar endoscopic diskectomy in discogenic lumbosacral
      radiculitis].
AB  - The paper presents the results of percutaneous lumbar endoscopic diskectomy in 96
      patients with discogenic lumbosacral radiculitis. Indications, contraindications,
      and surgical techniques are discussed. The intervention is shown to be highly
      effective (91.1%) in young patients with a relatively short history of the
      disease and hernias measuring as large as 8 mm. The paper analyzes complications
      and poor results of treatment using percutaneous lumbar endoscopic diskectomy.

PMID- 15724549
TI  - [Iatrogenic metastasis of pineal tumors].
AB  - Malignant pineal tumors (PT) tend to metastasize. In rare cases, this process is
      provoked by surgery. This paper describes four cases of iatrogenic metastasis of
      PT. Metastasis occurred: a) along the surgical approach path after tumor removal
      in 2 cases; b) along the biopsy cannula path; and c) along the
      ventriculoperitoneal catheter into the abdomen. The sources of metastases were
      pineoblastoma (n = 1), malignant teratoma (n = 1), germinoma (n = 1), and
      malignant germ-cell tumor of unknown genesis (n = 1). To prevent this
      complication due to high-grade PT, such as malignant germ-cell tumors and
      pineoblastomas, radiation of the whole brain, besides the sites of a tumor should
      be performed and, in some cases, in combination with chemotherapy.

PMID- 15724550
TI  - [Concurrence of Fahr's disease with cerebellar tumors].
AB  - Fara's disease or idiopathic calcification of the basal ganglia is a rare disease
      that is characterized by multiple petrificates in the area of the basal ganglia,
      caudate nucleus, and dentate nuclei of the cerebellum. As of now, only two cases
      of a concurrence of Fara's disease and brain tumors have been described. The
      authors present two more cases. Both cases are unique since the tumors occurred
      in the presence of Fara's disease symmetrically, as in the mirror, in the
      cerebellar hemispheres at the periphery of petrificates. This may be confirmed by
      the fact that astrocytic proliferation and hyperplasia around the calcified
      vessels are a cause of neoplasms.

PMID- 15724551
TI  - [Dislocation and impaction of the brain after purgetive enema].
AB  - The paper describes a case of dislocation and impaction of the brain in a child
      with a large brain tumor, which developed after purgetive enema. It also
      discusses the management of patients with this complication and possible ways of
      its prevention.

PMID- 15724553
TI  - [Resolution of the Presidium of the Board of the All-Russian Society of
      Neurologists. Results and prospects of the use of cellular technologies in the
      treatment of neurological diseases].

PMID- 15724552
TI  - [Osteoplastic laminotomy].
AB  - The paper describes the surgical technique of laminotomy. The basic stages of the
      operation and nuances of its performance are provided so that the readers can
      easily understand. Real photos of each surgical stage are useful for
      neurosurgeons dealing with intramedullary tumors.

PMID- 15724554
TI  - Patient safety authority enables sharing of lessons learned.
AB  - --The Pennsylvania Patient Safety Authority requires hospitals to report serious
      events and potentially harmful events. --Hospitals can be fined and physicians
      can lose licensing for failure to report events. --More than 50,000 events have
      been reported statewide since the system went on-line in July 2004.

PMID- 15724555
TI  - Tool forms foundation of approach to pediatric PI.
AB  - --All-patient refined diagnosis-related groups are used to analyze patient care
      data. --Pulmonologists and respiratory therapists help identify performance
      improvement opportunities and interventions. --Educational visits are a key
      element in achieving a lower rate for readmissions.

PMID- 15724556
TI  - Collaborative effort sees improvement in LOS.
AB  - --Consultant helps identify conditions with the greatest cost opportunity for
      improvement. --Bringing pulmonologist on board is one key to better protocols for
      congestive heart failure. --Clinic readmission rates are cut to 2.2%; lengths of
      stay also are reduced.

PMID- 15724557
TI  - Survey finds hospitals lagging behind on safety.
AB  - --Survey is first to include measures covering all 30 NQF-endorsed safety
      practices. --Protocols, policies, and procedures found lacking in many different
      areas. --Survey questions designed to help hospitals focus on potential areas of
      improvement.

PMID- 15724558
TI  - Tailored anesthesia aids safety post-surgery.
AB  - --Bispectral analysis technology enables more precise measuring of depth of
      consciousness. --The more traditional method, vital signs, now is seen as too
      nonspecific. --Patients awaken sooner, respond quicker, and experience less
      nausea, vomiting, and pain.

PMID- 15724559
TI  - Patient safety alert. Teaching/learning packets engender culture change.

PMID- 15724560
TI  - JCAHO issues roadmap on P4Ps, citing 'few well-articulated goals'.
AB  - --Well-defined programs can help avoid unintended consequences, according to the
      Joint Commission on Accreditation of Healthcare Organizations. --Principles
      stress aligning reimbursement with high quality and patient safety. --Quality
      experts see advantages in standardized measures for comparative data.

PMID- 15724561
TI  - VA gets high marks for preventive, chronic care.

PMID- 15724562
TI  - Hospitalists, pharmacists partner to cut errors.
AB  - --Pharmacy residents accompany hospitalists on rounds on a rotating basis. --The
      study is a logical extension of ongoing physician/pharmacist collaboration. -
      Payback extends beyond the program to physicians throughout the organization.

PMID- 15724563
TI  - Kiosks win patient kudos and speed registration.
AB  - --Program is part of systemwide clinical transformation initiative. --Self
      service technology is one way to make patient experience faster, safer, better. -
      Incremental revenue from more frequent appointments helps system pay for itself.

PMID- 15724564
TI  - Simulation center uses real-world training.
AB  - --Students, hospital staff, and faculty all participate in training sessions. -
      Facility provides ability to train and learn without harm to patients. -
      Scenarios can be created with specific learning in mind.

PMID- 15724565
TI  - Science-based recommendations to prevent or reduce potential exposure to
      biological, chemical, and physical agents in schools.
AB  - The U.S. General Accounting Office (GAO) documented generally poor conditions of
      school facilities in the early 1990s. Previous papers examined, for time
      intervals ending before 2002, relationships between education facility indoor air
      and environmental quality (IEQ), including adequate ventilation, and occupant
      health and productivity. Research on IEQ related specifically to new or
      refurbished traditional school construction, or portable classrooms, is limited.
      A review of school IEQ literature through fall 2003 was conducted. Then,
      acknowledging the limited resources and competing priorities facing American
      schools, practical science-based, best practices recommendations to promote IEQ
      and hence prevent or reduce potential occupant exposure to biological, chemical,
      and physical agents of concern were proposed. Electronic search engines,
      conference proceedings, the Internet, and reference lists of peer-reviewed papers
      and reports were used. Eighteen best practices based on scientific references are
      presented.

PMID- 15724566
TI  - Exercise level and energy expenditure in the TAKE 10! in-class physical activity
      program.
AB  - This study evaluated the effectiveness of an innovative, classroom-based physical
      activity prevention program designed to integrate academic curriculum elements
      along with a physical activity program in providing moderate-to-vigorous
      intensity physical activity. A convenience sample of three public school
      classrooms (one first, third, and fifth grade class) was observed implementing
      the TAKE 10! program while monitored by either CSA accelerometers or digital
      pedometers. Pedometer step counts and CSA data were recorded for each student and
      activity. As calculated from CSA data, average MET levels during the activities
      were 5.72-7.05 (first grade), 5.51-6.77 (third grade), and 4.98-7.19 (fifth
      grade), and levels were not different between grades (p > 0.05). Average caloric
      expenditure (Kcal) per 10-minute session was 25.6-27.8 (first grade), 27.6-33.9
      (third grade), and 29.7-42.9 (fifth grade). Measured pedometer step counts per
      session ranged from 644-931 in first grade, 659-1, 376 in third grade, and 1002
      1041 in fifth grade. TAKE 10! sessions for all three grades produced exercise
      levels in the moderate intensity range throughout full duration of the session.
      Classroom-based physical activity promotion provides a useful strategy to promote
      meaningful physical activity among school children.

PMID- 15724568
TI  - Environmental health: you write the future.

PMID- 15724567
TI  - Assessing prevalence of overweight and obesity through self-reports of height and
      weight by high school students in Taipei, Taiwan.
AB  - This study compared consistency of age- and gender-specific self-reported height
      and weight and calculated body mass index among a sample of high school students
      in Taipei County, Taiwan to reference values for Taiwanese school-aged youth
      obtained through national studies. Taipei high school students provided self
      reports of height and weight that were similar to national reference values. Use
      of self-reported height and weight in this sample appeared warranted and may
      reliably be used to calculate aggregate indices of body mass, overweight, and
      obesity. This study compared prevalence of overweight and obesity in the current
      sample with other adolescent populations using international criteria
      (International Task Force on Obesity). Using these criteria, 17.6% of boys and
      9.4% of girls met the definition of overweight and 3.7% of boys and 1.6% of girls
      met the definition of obesity. While use of self-reported height and weight
      appears justified in this sample, researchers should not assume self-report
      measures will always be accurate. Researchers considering use of self-reported
      height and weight should compare their results to normative reference values when
      possible to increase confidence in using self-report measures of height and
      weight.

PMID- 15724569
TI  - Intestinal parasites in children from three west Texas border communities.

PMID- 15724570
TI  - Policy and research issues for small assisted living facilities.
AB  - Dramatic growth in Assisted Living (AL) has resulted in increasing research and
      policy interest. This analysis compares smaller and larger AL facilities in four
      states to determine whether extant measures of four key concepts, used to
      distinguish the AL sector, give advantage to larger facilities. Quantitative
      comparisons predominantly show differences favorable to larger facilities;
      qualitative information raises the prospect that current measures overlook
      beneficial aspects of smaller facilities. If small facilities are included under
      the AL banner. both policy provisions and quality assessment must be carefully
      crafted to avoid placing small homes in funding and oversight jeopardy as AL
      develops.

PMID- 15724571
TI  - The influence of financial incentives and racial status on the use of post
      hospital care.
AB  - This study examines the influence of financial incentives and the racial status
      of the patient on the use of extended care following an episode of
      hospitalization. Post-hospital care (PHC) is defined as the services provided by
      a skilled nursing facility (SNF) or intermediate care facility (ICF) following
      discharge. The focus of the analysis is on the use or nonuse of PHC, the presence
      or absence of a delay in transfer to an ICF or SNF and, limited to those who
      experienced a postponement, the length of the delayed discharge. After
      controlling for multiple factors, the results indicate that Medicare
      beneficiaries were more likely to use PHC, less likely to experience a delay in
      discharge, and used fewer days of prolonged care. Medicaid recipients and
      uninsured patients experienced reduced access to PHC. The results also indicated
      that the access of Native Americans and Americans to PHC was impeded.

PMID- 15724572
TI  - Do notional defined contribution accounts make sense as part of the old-age
      security mix for China?
AB  - Until quite recently, the Chinese pension system was an enterprise-based, pay-as
      you-go, defined benefit scheme. In 1995, the decision was made to shift to a
      multi-pillar scheme that included a second funded defined contribution pillar.
      The transition is proving difficult. This article outlines an alternative second
      pillar that may make more sense for China, a pay-as-you-go notional defined
      contribution (NDC) pillar. This article has three goals: (1) to provide a brief
      history of pension policy in China, (2) to describe the NDC model, and (3) to
      assess the relative merits of the NDC alternative as a possible option for China.

PMID- 15724573
TI  - Aging in the shadow of the law: the case of elder guardianship in Israel.
AB  - Historically, the frail elderly, as well as other vulnerable populations who are
      unable to care for themselves, have been subject to legal proceedings known as
      guardianships. Despite changes and reforms, adult guardianship law has survived
      as a fundamental legal institution aimed at protecting the frail elderly as well
      as other incompetent adults. However, very little is known on the reality of
      adult guardianship under Israeli law, and the experience of the adult population
      under guardianship was never empirically studied in Israel. The empirical void
      regarding the workings of the Israeli law in this area served as the impetus for
      this study. The study investigated the issue of adult and elder guardianship in
      Israel as revealed in Family Law Courts' rulings, while focusing in particular on
      the profile of the wards, the reasons and motives, the legal procedure, and the
      outcome of the guardianship process. The study was a quantitative analysis, based
      on a random sample that included 523 court cases requesting legal guardianship
      for adults due to impaired legal competence. Rulings on these cases were provided
      in Family Courts from Haifa, Nazareth, and the Krayot areas in the period of the
      years 2000-2002. A clear but somber picture emerges from the findings of this
      study: Every year thousands of elderly individuals are subjected to the plenary
      legal authority of guardians appointed by law. This severe legal outcome takes
      place without providing these elderly the right to express their positions,
      without the provision of legal representation, and without their being seen or
      heard by the courts. These findings lead to the conclusion that there is urgent
      need in Israel to carry out extensive reform in the realm of civil legislation on
      the issue of guardianship for adults and the elderly.

PMID- 15724574
TI  - Preventing economic hardship among Chinese elderly in Hong Kong.
AB  - Over the next 20 years, Hong Kong will face a rapidly aging population as the
      number of older adults aged 65 or above increases to approximately 1.4 million by
      2021, that is, 17% of the total population. In 2001, there were 1.2 million
      adults aged 45-59. To assess the differences between these middle-aged adults and
      the current cohort of older adults, we identified the challenges that Hong Kong
      society will face in meeting the financial needs of older adults in the coming
      two decades. In this paper, we examine the retirement economic status of three
      groups of older adults: those who are financially independent, those who are
      financially supported by their adult children or children-in-law, and those who
      are receiving welfare assistance. We describe the current situations of these
      groups, prevailing social policy, future trends, and recommend policies for
      tackling problem areas.

PMID- 15724575
TI  - Ending the CEO succession crisis.
AB  - The CEO succession process is broken. Many companies have no meaningful
      succession plans, and few of the ones that do are happy with them. CEO tenure is
      shrinking; in fact, two out of five CEOs fail in their first 18 months. It isn't
      just that more CEOs are being replaced; it's that they're being replaced badly.
      The problems extend to every aspect of CEO succession: internal development
      programs, board supervision, and outside recruitment. While many organizations do
      a decent job of nurturing middle managers, few have set up the comprehensive
      programs needed to find the half-dozen true CEO candidates out of the thousands
      of leaders in their midst. Even more damaging is the failure of boards to devote
      enough attention to succession. Search committee members often have no experience
      hiring CEOs; lacking guidance, they supply either the narrowest or the most
      general of requirements and then fail to vet eitherthe candidates or the
      recruiters. The result is that too often new CEOs are plucked from the well-worn
      Rolodexes of a remarkably small number of recruiters. These candidates may be
      strong in charisma but may lack critical skills or otherwise be a bad fit with
      the company. The resulting high turnover is particularly damaging, since outside
      CEOs often bring in their own teams, can cause the company to lose focus, and are
      especially costly to be rid of. Drawing on over 35 years of experience with CEO
      succession, the author explains how companies can create a deep pool of internal
      candidates, how boards can consistently align strategy and leadership
      development, and how directors can get their money's worth from recruiters.
      Choosing a CEO should be not one decision but an amalgam ofthousands of decisions
      made by many people every day over years.

PMID- 15724576
TI  - Productive friction: how difficult business partnerships can accelerate
      innovation.
AB  - Companies are becoming more dependent on business partners, but coordinating with
      outsiders takes its toll. Negotiating terms, monitoring performance, and, if
      needs are not being met, switching from one partner to another require time and
      money. Such transaction costs, Ronald Coase explained in his 1937 essay "The
      Nature of the Firm," drove many organizations to bring their activities in-house.
      But what if Coase placed too much emphasis on these costs? What if friction
      between companies can be productive? Indeed, as John Hagel and John Seely Brown
      point out, interactions between organizations can yield benefits beyond the goods
      or services contracted for. Companies get better at what they do--and improve
      faster than their competitors--by working with outsiders whose specialized
      capabilities complement their own. Different enterprises bring different
      perspectives and competencies. When these enterprises tackle a problem together,
      they dramatically increase the chances for innovative solutions. Of course,
      misunderstandings often arise when people with different backgrounds and skill
      sets try to collaborate. Opposing sides may focus on the distance that separates
      them rather than the common challenges they face. How can companies harness
      friction so that it builds capabilities? Start by articulating performance goals
      that everyone buys into. Then make sure people are using tangible prototypes to
      wrangle over. Finally, assemble teams with committed people who bring different
      perspectives to the table. As individual problems are being addressed, take care
      that the underpinnings of shared meaning and trust are also being woven between
      the companies. Neither can be dictated--but they can be cultivated. Without them,
      the performance fabric quickly unravels, and business partnerships disintegrate
      into rivalrous competition.

PMID- 15724577
TI  - Should nonprofits seek profits?
AB  - Twenty years ago, it would have been shocking for a children's choir to sell
      singing telegrams or for an organization serving the homeless to dabble in
      property management. Today, it seems routine. Nonprofits increasingly feel
      compelled to launch earned-income ventures--not only to appear more disciplined
      and businesslike to stakeholders but also to reduce their reliance on
      fundraising. There's plenty of hype about the value of earned-income ventures in
      the nonprofit world, but such projects account for only a small share offunding
      in most nonprofit domains, and few of the ventures make money. Moreover, when the
      authors examined how nonprofits evaluate potential enterprises, they discovered a
      pattern of unwarranted optimism. The potential financial returns are often
      exaggerated, and the challenges of running a successful business are routinely
      discounted. But the biggest downside of such ventures is that they can distract
      nonprofits' managers from their core social missions and, in some cases, even
      subvert those missions. There are several reasons for the gap between the hype
      and the reality. One is that an organization's nonfinancial concerns-such as a
      desire to hire the disadvantaged-can hamper it in the commercial marketplace.
      Another is that nonprofits' executives tend to overlook the distinction between
      revenue and profit. For example, a youth services organization that had received
      funding to launch a food products enterprise hired young people and began making
      salad dressing. The nonprofit believed it spent $3.15 to produce each bottle of
      dressing that was sold for $3.50. But when expenses such as unused ingredients
      and managers' salaries were factored in, the cost per bottle reached a staggering
      $90. Earned-income ventures do have a role in the nonprofit sector, the authors
      say, but unrealistic expectations are distorting managers' decisions, wasting
      precious resources, and leaving important social needs unmet.

PMID- 15724578
TI  - Change through persuasion.
AB  - Faced with the need for a massive change, most managers respond predictably. They
      revamp the organization's strategy, shift around staff, and root out
      inefficiencies. They then wait patiently for performance to improve--only to be
      bitterly disappointed because they've failed to adequately prepare employees for
      the change. In this article, the authors contend that to make change stick,
      leaders must conduct an effective persuasion campaign-one that begins weeks or
      months before the turn-around plan is set in concrete. Like a political campaign,
      a persuasion campaign is largely one of differentiation from the past. Turnaround
      leaders must convince people that the organization is truly on its deathbed-or,
      at the very least, that radical changes are required if the organization is to
      survive and thrive. (This is a particularly difficult challenge when years of
      persistent problems have been accompanied by few changes in the status quo.) And
      they must demonstrate through word and deed that they are the right leaders with
      the right plan. Accomplishing all this calls for a four-part communications
      strategy. Prior to announcing a turnaround plan, leaders need to set the stage
      for employees' acceptance of it. At the time of delivery, they must present a
      framework through which employees can interpret information and messages about
      the plan. As time passes, they must manage the mood so that employees' emotional
      states support implementation and follow-through. And at critical intervals, they
      must provide reinforcement to ensure that the desired changes take hold and that
      there's no backsliding. Using the example of the dramatic turn-around at Boston's
      Beth Israel Deaconess Medical Center, the authors elucidate the inner workings of
      a successful change effort.

PMID- 15724579
TI  - Transforming an industrial giant. Interview by Thomas A. Stewart and Louise
      O'Brien.
AB  - In his 12 years at the helm of Siemens, CEO Heinrich von Pierer designed and
      directed a major transformation. Taking this German icon from a technically
      superb but slow-moving industrial giantto a disciplined yet nimble multinational
      has posed enormous challenges. Since 1992, Siemens has revamped its portfolio of
      businesses, expanded its reach into 192 countries, and created a more local
      market-driven culture, gaining recognition as one of the best-managed and most
      competitive companies in the world. In this edited interview with HBR editor
      Thomas A. Stewart and consulting editor Louise O'Brien, von Pierer describes the
      requirements for transformation and culture change and how he broke down
      historical barriers at Siemens. He shares his insights about portfolio
      restructuring, his lessons from competing with GE, and the pros and cons of being
      based in Europe versus America. He reflects on the true start of globalization
      after the fall of the Berlin wall and on how dramatically the company needed to
      change in order to counter the resulting pricing pressures across all of its
      businesses. He talks, too, about the biggest challenge on his successor's desk
      "the particular challenge of China;" he says. Amid all these topics, von Pierer
      reiterates the importance of people: "We all talk about people as our most
      important resource, but as a matter of fact, who's really taking care of
      people?... We need [their] backing. We can't afford to run into a situation where
      people no longer accept what we do."

PMID- 15724580
TI  - Two executives, one career.
AB  - For six years, Cynthia Cunningham and Shelley Murray shared an executive job at
      Fleet Bank. One desk, one chair, one computer, one telephone, and one voice-mail
      account. To their clients and colleagues, they were effectively one person,
      though one person with the strengths and ideas of two, seamlessly handing
      projects back and forth. Although their department was dissolved after the bank
      merged with Bank of America, the two continue to consider themselves a package
      they have one resume, and they are seeking their next opportunity together. Their
      choice to share a job was not only a quality-of-life decision but one intended to
      keep their careers on course: "Taking two separate part-time jobs would have
      thrown us completely off track" they write in this first-person account."We're
      both ambitious people, and neither of us wanted just a job. We wanted careers" In
      this article, the two highly motivated women reveal their determination to manage
      the demands of both family and career. Flextime,telecommuting, and compressed
      workweeks are just some of the options open to executives seeking greater work/
      life balance, and the job share, as described by Cunningham and Murray, could
      well be the next solution for those wishing to avoid major trade-offs between
      their personal and professional lives. Cunningham and Murray describe in vivid
      detail how they structured their unusual arrangement, how they sold themselves to
      management, and the hurdles they faced along the way. Theirs is a win-win story,
      for the company and for them.

PMID- 15724581
TI  - Strategic sourcing: from periphery to the core.
AB  - As globalization changes the basis of competition, sourcing is moving from the
      periphery of corporate functions to the core. Always important in terms of costs,
      sourcing is becoming a strategic opportunity. But few companies are ready for
      this shift. Outsourcing has grown so sophisticated that even critical functions
      like engineering, R&D, manufacturing, and marketing can-and often should-be moved
      outside. And that, in turn, is changing the way companies think about their
      organizations, their value chains, and their competitive positions. Already, a
      handful of vanguard companies are transforming what used to be purely internal
      corporate functions into entirely new industries. Companies like UPS, Solectron,
      and Hewitt have created new business models by concentrating scale and skill
      within a single function. As these and other function-based companies grow, so
      does the potential value of outsourcing to all companies. Migrating from a
      vertically integrated company to a specialized provider of a single function is
      not a winning strategy for everyone. But all companies need to rigorously
      reassess each of their functions as possible outsourcing candidates. Presented in
      this article is a simple three-step process to identify which functions your
      company needs to own and protect, which can be best performed by what kinds of
      partners, and which could be turned into new business opportunities. The result
      of such an analysis will be a comprehensive capabilities-sourcing strategy. As a
      detailed examination of 7-Eleven's experience shows, the success of the strategy
      often hinges on the creativity with which partnerships are organized and managed.
      But only by first taking a broad, strategic view of capabilities sourcing can
      your company gain the greatest benefit from all of its sourcing choices.

PMID- 15724582
TI  - Tending to Social Security.

PMID- 15724584
TI  - The fix-everything plan.

PMID- 15724583
TI  - At GM, there's health to pay.

PMID- 15724585
TI  - [Ocular melanoma].
AB  - Ocular melanoma is a rare tumour with a poor prognosis when initial tumour burden
      is large. In France, the disease incidence is estimated to 7/1,000,000 persons.
      Except for the presence of an Ota's naevus, no risk factor has been clearly
      identified. In many patients, radiotherapy offers an alternative local therapy to
      surgery. No adjuvant treatment has demonstrated any benefit. Treatment of
      metastatic disease has to be precised.

PMID- 15724586
TI  - [Cochlear implant in adults].

PMID- 15724587
TI  - [A problem of public health neglected in spite of effective diagnostic and
      therapeutic means].

PMID- 15724588
TI  - [Diagnosis of osteoporosis].
AB  - Osteoporosis is the main cause of bone fragility. The diagnosis is suspected in
      the presence of low-energy traumatic fracture and/or low bone mineral density.
      Vertebral fractures may be asymptomatic, and they are under-diagnosed. Dual
      energy X-ray absorptiometry is the gold standard of bone density measurement, at
      the lumbar spine, and hip. Providing quality control of the device and
      assessments, the measurements are accurate and precise; BMD is the basis of
      osteoporosis diagnostic and risk fracture evaluation. Osteoporosis may be related
      to malignant and metabolic diseases, which must be checked before any treatment.

PMID- 15724589
TI  - [Treatment of postmenopausal osteoporosis].
AB  - The treatment of postmenopausal osteoporosis relies on management of some risk
      factors for fracture, e.g., risk factors for falls, improvement of calcium and
      vitamin D intake, and on various medications. All elderly women with calcium and
      vitamin D deficiency should receive calcium and vitamin D supplements. Estrogen
      replacement therapy should not longer be used to prevent or treat postmenopausal
      osteoporosis, owing to its poor long-term risk/benefit ratio. Raloxifene,
      biphosphonates (alendronate, risedronate) are well tolerated compounds with
      proven anti-fracture efficacy. Teriparatide is a new bone forming agent to treat
      severe osteoporosis. Strontium ranelate is a new drug also reducing the risk of
      fractures that should be available soon.

PMID- 15724590
TI  - [Osteoporosis in men].
AB  - Less comon than in women, osteoporosis in men may be idiopathic, but in about 60%
      of patients several factors contribute to bone loss and fractures. The most
      prominent causes of secondary osteoporosis in males are hypogonadism,
      corticosteroid therapy, alcohol abuse, and gastrointestinal or hepatic disorders.
      Testosterone treatment is reserved to the treatment of hypogonadal men. In
      primary or secondary male osteoporosis, diphosphonates prevent bone loss and
      reduce the incidence of future fractures.

PMID- 15724591
TI  - [Corticosteroid-induced osteoporosis].
AB  - Osteoporosis and fractures are the frequent consequences of corticosteroid
      therapy. Cancellous bone is primarily affected with a decrease of bone formation
      and an increase of bone resorption. Prevention of corticosteroid-induced
      osteoporosis is based upon general measures such as calcium and vitamin D
      supplementation, adequate protein intake, regular physical exercise, and upon
      specific therapies like those used in primary osteoporosis. Biphosphonates, which
      are potent bone resorption inhibitors, have been shown to increase bone mineral
      density and to decrease vertebral fracture rate. Therefore, they appear to be a
      first choice in the prevention of corticosteroid-induced osteoporosis.

PMID- 15724592
TI  - [First-year enrollment in French medical schools].

PMID- 15724593
TI  - [Acute anxiety and panic attack].

PMID- 15724594
TI  - [Primary and secondary tumours of the bones].

PMID- 15724595
TI  - [Crohn's disease and ulcerative colitis].

PMID- 15724596
TI  - [The electrocardiogram. Indications and interpretation].

PMID- 15724597
TI  - [Blood transfusion and blood-derived products: indications, complications.
      Haemovigilance].

PMID- 15724598
TI  - [Autoimmune pathologies. Epidemiological and diagnostic aspects, principles of
      treatment].

PMID- 15724599
TI  - [Military hospitals models for civilian hospitals].

PMID- 15724600
TI  - [Erythrocyte sedimentation rate in diagnostics and prognosis of diseases].
AB  - The article presents data concerning clinical and laboratory diagnostics of
      different diseases and the importance of determination of the erythrocyte
      sedimentation rate in it. In 1924 (80 years ago) the first work of T. P.
      Panchenko about the macromethod of the determination Erythrocyte sedimentation
      rate and its importance in clinical and laboratory diagnostics was published in
      the medical journal "Vrachebnoe Delo". Although this method is not specific, it
      integrally reflects general derangements of the organism's homeostasis in
      patients with acute and chronic diseases and allows controlling sanogenese and
      completing recovery processes. Nowadays this method is still actual in
      physician's practice.

PMID- 15724602
TI  - [Frequency dynamics of stomach and duodenum ulcer found in liquidators of
      consequence of Chernobyl accident (according to the data of long-term
      observation)].
AB  - The authors have studied the frequency dynamics of stomach and duodenum ulcer
      occurrence revealed in liquidators of consequence of Chernobyl accident (1986
      1987) after long-term medical observation with age and radiation absorbed dose
      variations. According to the findings, duodenum ulcer incidence prevails over
      stomach ulcer in all scale of age. The connection between the frequency dynamics
      of duodenum ulcer and age of the patients wasn't found.

PMID- 15724601
TI  - [Comparative characteristic of blood vessels filling, venous drainage and venous
      congestion in patients with autonomic vascular dystonia and arterial hypertention
      who have suffered from Chernobyl accident (according to the data of
      rheoencephalography and rheovasculagraphy)].
AB  - Reliable differences in venous drainage and venous congestion and blood vessels
      filling of cerebral hemispheres in patients with vegetovascular dystonic and
      arterial hypertention who have suffered from Chernobyl accident have been
      detected by means of impedance tetrapolar plethysmography (rheoanalyzer PA5-01).

PMID- 15724603
TI  - [Lymphocyte subpopulation changes in children with chronic virus hepatitis D and
      B].
AB  - We observed 367 children with chronic viral hepatitis Delta (CVHD) and B (CVHB)
      and found strict secondary T-immunodeficiency, more expressed in children with
      CVHD. We have found also the most characterizing changes of lymphocytes
      subpopulation and natural killer-cells depending on etiology of CVH. As for CVHD
      it is characterized by more significant decrease in CD4-lymphocytes, as for CVHB-
      CD8-lymphocytes. The above mentioned changes of lymphocytes subpopulation in
      patients with CVHD and CVHB show different pathological mechanisms of these two
      diseases, that should be taken into account treating such patients.

PMID- 15724604
TI  - [The role of antioxidant defense system in the development of glycemic disorders
      in patients with lung tuberculosis].
AB  - The development of different carbohydrate metabolism disorders in patients with
      lung tuberculosis occurs against a background of significant derangements in
      oxidation-reduction system, caused by hypoxia and intoxication. The classical
      antituberculosis treatment within 2 months doesn't succeed in normalization of
      functional activity of enzymes of the antioxidant defense system and doesn't
      eliminate carbohydrate metabolism disorders.

PMID- 15724605
TI  - [The role of asymptomatic bacteriuria in epidemiologic study of the urinary tract
      infection].
AB  - Asymptomatic bacteriuria as a major criterion of urinary tract infection (UTI)
      was revealed in 597 (25.6%) of 2.330 rural inhabitants under study. In adults
      that value (25.3%) appeared to be lower to some extent as compared with children
      (at age 1 to 14)--27.2% (P>0.5). At the same time asymptomatic bacteriuria
      occurred reliably more frequent in females as compared with males, 50.3% and
      14.7% correspondingly (P<0.001). Use of the asymtomatic bacteriuria sign in
      epidemiological studies allows to reveal early stages of UTI and carry out
      prophylactics of the disease timely.

PMID- 15724606
TI  - [Changes in indices of connective tissue in patients with alcoholic and non
      alcoholic steatohepatitis and their correction with glutargin].
AB  - The study of protein and carbohydrate components of extracellular matrix in
      patients with alcoholic and non alcoholic steatohepatitis developed on the
      background of type 2 diabetes mellitus has shown a significant increase in
      collagen and glycosaminoglycan synthesis along with the enhancement of
      proteolytic and compensatory collagenous activity of blood plasma in patients
      with alcoholic steatohepatitis and inhibition of collagenolytic and proteolytic
      activity of blood plasma in patients with non alcoholic steatohepatitis against
      the background of diabetes mellitus, decrease in glycoprotein synthesis.
      Glutargin enhances metabolism of connective tissue by impeding collagen and
      glycosaminoglycan synthesis, activating proteoglycan production, augmenting blood
      plasma activity in patients with non alcoholic steatohepatitis, hindering
      proteolysis in patients with alcoholic steatohepatitis as well as increasing the
      excretion of connective tissue metabolites through urinary tracts.

PMID- 15724608
TI  - [Considerable decrease in chemokine interleukin-16 level in blood of children
      with diabetes mellitus type I diagnosed for the first time].
AB  - Considerable decrease in chemokine interleukin-16 level has been detected in
      blood serum of children with the first diagnosed in life diabetes mellitus type
      I.

PMID- 15724607
TI  - [Incidence of proliferative retinopathy and sex-related differences in death rate
      among patients with diabetes mellitus and sight impairment treated with insulin
      (according to the data from national diabetic registry)].
AB  - The article presents the analysis of the occurrence of diabetes mellitus-linked
      sight impairment and proliferative retinopathy after data of National Diabetes
      Population Register among patients receiving insulin therapy. The number of women
      with above mentioned impairments has been found to prevail significantly over
      that of men. This tendency is also observed among the patients aged to 50 y. o.,
      although in this age group the number of men with diabetes mellitus prevails over
      that of women. This discrepancy can be explained through higher death rate linked
      with diabetes mellitus among men as compared with women. Death rate statistics
      concerning patients with diabetes mellitus complicated with sight impairment for
      2003 y. confirms this supposition.

PMID- 15724609
TI  - [Effect of perindopril on hemostasis and functional status of pancreas in
      patients with ischemic heart disease].
AB  - Systemic circulation compromise in patients with cardiac insufficiency results in
      disturbances of functional state of pancreas. The Willebrand's Factor takes a
      definite role in this pathological process. The usage of Peridopril 4 mg daily
      during the treatment decreases significantly Willebrand's Factor activity and
      normalizes function of the pancreas.

PMID- 15724610
TI  - [Selection of methods of reconstructive operations in surgical treatment of
      unspecific ulcerative colitis].
AB  - Chromocolonoscopic diagnostics in recognizing of displastics lisions of mucosa is
      described in the article. The indications for different methods of reconstructive
      operations are presented.

PMID- 15724611
TI  - [Selection of prognostic criteria for external respiration function during
      surgical treatment of progressive cholelithiasis].
AB  - Studying risk factors of developing damage and complication of cardio-respiratory
      system it was established that indices of external respiration system function
      such as respiratory minute volume, general oxygen uptake are reliable in
      forecasting consequences of surgical treatment of cholelithiasis. Availability of
      inspection and calculation methods makes it possible to recommend these indices
      to fully implement in Health Care to control treatment quality in patients with
      acute surgical diseases.

PMID- 15724612
TI  - [Effect of magnetic and ultrasound therapy on clinical manifestations and general
      parameters of efficiency in the treatment of pulmonary tuberculosis].
AB  - The authors have analized general efficiency coefficients of the treatment of 117
      patients with the first diagnized pulmonary tuberculosis. The patients were
      divided into a control and main group. 61 patients of the main group at the
      initial stage of complex treatment in addition to a standard chemotherapy have
      recieved magnetic and ultrasound therapy. During the treatment the patients
      underwent complex clinical and X-ray examination. The patients of the main group
      have been detected to have better signs of recovering compared with the control
      group. The signs were the following: more rapid disappearing of main clinical
      symptoms, radiological marks of tuberculosis such as focal and infiltrative
      alterations and decay cavity closing, cessation of bacterioexcretion.

PMID- 15724613
TI  - [Brain metabolites ratio as a prospective marker in assessment of the therapy
      efficacy in children with epilepsy].
AB  - Influence of ratio between N-acetylaspartat (NAA) and myoinositol brain tissue
      metabolites as well as ratio beween myoinositol and kreatinine on the therapy
      efficacy in children with epilepsy has been studied by authors. The obtained
      results allowed detecting the derangement in one section of cerebral metabolism,
      recovery of which on the background of effective antiepileptic treatment finds
      its reflection in ratio between N-acetylaspartat (NAA) and myoinositol and
      between myoinositol and kreatinine.

PMID- 15724614
TI  - [Clinical and rheovasographic correlations in patients with lumbosacral pain
      syndrome in the complex treatment using underwater vertical extension].
AB  - The article presents the findings of using underwater vertical extension in a
      complex treatment of patients with lumbosacral pain syndromes. The rheovasography
      method has been applied. Underwater vertical extension method in a complex
      treatment of patients with lumbosacral pain syndromes was found to be effective
      according to clinical data and positive dynamics of rheovasography's indices.

PMID- 15724615
TI  - [The surgical treatment of malignant adrenal chromaphinomas].
AB  - Pheochromoblastoma (PHB) is a tumor developing from adrenal medulla and
      characterized by severe course and high mortality level (15%). The severity of
      patients' state determined not only by presence of cancerous growth, but also due
      to catecholamine hyperproduction. The author has analyzed the results of surgical
      treatment of 60 patients with PHB, which were in surgical clinic during 1968-2002
      y.y. The most effective method of the treatment is surgery. The method of choice
      is a lumbotomic extraperitoneal approach. The eradication of malignant growth
      requires not only complete tumor removal in single capsule with the adrenal gland
      but also thorough revision of paranephric, paracaval and paraaortal lymphnodes.
      38 patients (63.3%) from 60 underwent radical surgery followed by long-term
      remission. The remission of the disease in 3 patients (5%) was achieved only
      after reoperations. The disease persists in two patients though it is better
      controlled after the operation than earlier with medicine. 8 (13.3%) patients
      were diagnosed to have widespred metastases and were referred to symptomatic
      treatment. The recurrence of the disease after the primary surgery is a bad
      forecasting factor. The majority of the patients (55.8%) with the recurrence were
      incurable. In the rest of the cases the operative treatment led to the longterm
      remission only in 71.9% of the patients.

PMID- 15724616
TI  - [Effectiveness of a modified Madde-type mastectomy in patients with breast cancer
      of I-II stage].
AB  - Effectiveness of mastectomy with two breast muscles preserved and total
      lymphdissection (Malden surgical operation) in I-II stage breast cancer patients
      has been studied. The control group has been operated using classical mastectomy
      after Golsted and its modified variant named after Peity. The degree of the
      disease dissemination was confirmed pathohistologicaly based on the 5-th edition
      of TNM system. It was established that the 5 year survival period among patients
      with primary tumor size getting pT1-2 doesn't depend on a volume of a surgical
      operation but correlates with the number of regional lymph nodes metastasis
      (pN1). It has totaled 85.3-87.2 % among pT1 pNO MO breast cancer patients, 73.5%-
      pT2 pNo MO, 63.7-69.3%--pT1-2pN1Mo. 81% of patients who had 1-3 regional lymph
      nodes metastasis is still alive after the 5 year survival period--57.2%, of those
      who had 4-9 regional metastasis overpassed this 5 year survival period and 10 or
      over regional metastasis survive only about 19%.

PMID- 15724617
TI  - [Two cases of diverticular disease of the digestive tract].
AB  - The presented observations of the development of diverticula and further
      progression of diverticulosis of digestive system give an evidence and prove up
      the interconnection between neurohumaral regulation of gall-bladder functions and
      intestine.

PMID- 15724618
TI  - [Morphologic effect of finoptin and obzidane on intact ventricular cardiac
      myocytes].
AB  - Finoptin and obzidane influence on morphologic signs of intact ventricular
      cardiac hystiocytes has been examined during the experiments on animals by means
      of the complex of histological and histochemical methods, electron microscopy as
      well as morphometry. It has been established that long-term using of finoptin and
      obzidane medication to intact animals does not affect cardiac hystiocytes.
      Finoptin can increase the thickness of the glycocalix layer and partly block Ca2+
      -binding locus of plasmolemma. Obzidane introduction enables to ensure constant
      energy-efficient, plastic and membrane-stabilizing effect. The medications use
      resulted in forming favorable initial conditions for increase in myocardium
      resistance to coronary insufficiency.

PMID- 15724619
TI  - [Laser puncture in the treatment of reflectory manifestations of lumbosacral
      osteochondrosis in elderly patients in geriatric hospital].
AB  - Peculiarities of involution age are of great importance choosing treatment
      methods. Laser puncture was shown to be an effective method in treatment of pain
      syndromes in elder patients with lumbosackul radiculitis. Combination of
      pharmacotherapy, laser stimulation, acupuncture, vaccum massage, bishophit use
      enhances considerably efficiency of the treatment.

PMID- 15724620
TI  - [Effect of omega-3 polyunsaturated fatty acids of animal origin on changes in
      regulation of lipid peroxidation in patients with ischemic heart disease].
AB  - The study's results showed reliable decrease in lipid peroxidation activity
      according to value of general sum of light, induced by hydrogen peroxide of
      initiated hemoluminescence and malonic dialdehyde concentration (P<0.05). The
      activity of antioxidant enzymes in the second group as compared with the control
      one has changed as follows: catalase concentration of blood serum of patients
      with ischemic heart disease increased by 59.49% (P<0.05), superoxide dismutase
      concentration--decreased by 28.64% (P<0.05). The above mentioned changes show,
      that the treatment with Tecom medication, which consist of omega-3
      polyunsaturated fatty acids of animal origin does not stress peroxid antioxidant
      system, does not affect cell membrane stability, does not lead to progression of
      ischemic heart disease course.

PMID- 15724621
TI  - [Efficiency of groprinosine in the complex treatment of acute virus hepatitis B].
AB  - 35 patients with acute virus hepatitis of average severity were examined. They
      developed after short-term improvement of general state a negative dynamics of
      clinical and laboratory indexes. 21 patients have received traditional treatment,
      14 patients additionally were prescribed groprinosine in a dose of 50 mg/kg daily
      per/os within 5-10 days. It was shown, that addition of gropfmosme to complex
      therapy positively influenced on the disease's course, promoted a rapid regress
      of clinical symptoms, normalization of biochemical indexes of liver's functions
      and decreased days of hospitalization.

PMID- 15724622
TI  - [Use of recombinant activated factor VII (NovoSeven) in the treatment of a
      patient with idiopathic thrombocytopenic purpura complicated with subarachnoid
      and parenchimatous hemorrhage].
AB  - Efficiency of recombinant activated factor VII (rFVIIa) (NovoSeven) in treatment
      of patients with idiopathic thrombocytopenic purpura (ITP) complicated with
      subarachnoid and parenchimatous hemorrhage was shown in the article. The action
      of NovoSeven in patients with an affected megakaryocytic system depends on the
      binding of rFVIIa with activated thrombocites and on their surface rFVIIa
      provides the activation of X factor and thrombin formation. NovoSeven proved to
      be called a universal hemostatic medication for the idiopathic thrombocytopenic
      purpura treatment. Taking into account that transfusion of thrombocites
      concentrate is not recommended for patients with thrombocytopenia of immune
      origin and after immunoglobulin infusion we need time to see thrombocites number
      grow so in urgent NovoSeven is a medication of choice to stop bleeding in
      patients with ITP.

PMID- 15724623
TI  - [Efficiency of encefabol use in patients with dyscirculatory encephalopathy].
AB  - The article presents the findings of the Encefabol treatment of 50 patients aged
      56-68 yy with vascular encephalopathy at the I-III stage, caused by
      atherosclerotic and high blood pressure pathological processes. The individual
      dose prescription of the medication to patients with vascular encephalopathy was
      substantiated in the article. The importance of psychodiagnostic tests in
      assessment of Encefabol treatment efficiency of the disease was shown in the
      article.

PMID- 15724625
TI  - [Eclecticism in medicine].
AB  - Last years saw a series of publications published in different medical editions,
      concerning an application sphere of physiotherapy. These publications cast doubt
      on reflexotherapy as an independent medical discipline. New term physiopuncture
      was proposed in such publications, actually it is a try terminologically and in
      practice to substitute acupuncture and its methods (i.e. reflexotherapy) by an
      other medical specialty physiotherapy. The article does not call physiotherapy in
      question as a specialty itself, but conclude, that such forcible attribution of
      the reflexotherapy's methods to physiotherapy's is not acceptable. All physical
      influences on the acupuncture's points (laserpuncture, electropuncture, shortwave
      frequency puncture and others) even that being used barely through metameric
      principle in accordance with WHO recommendations should be referred to the sphere
      of reflexotherapy.

PMID- 15724624
TI  - [Effect erythropoietin-beta on parameters of erythropoiesis and immunity in
      patients with diabetes mellitus complicated with diabetic neuropathy and anemia].
AB  - Erythropoiesis indices, number of leucocytes in 1 ml of blood, leukocytic
      formula, lymphocytes immunophenotype in the patients' blood with diabetes
      mellitus complicated with diabetic neuropathy and marked normochromal anemia
      after the treatment with Erythropoietin b have been analyzed in the study.
      Significant increase in haemoglobin, erythrocytes content, hematocrit indices of
      peripheral blood has been observed during the treatment. The patients felt
      better, their quality of life improved, CD3+, CD4+, CD5+ cells and granule
      contained lymphocytes content normalized. Serious adverse affects of the
      medication haven't been observed in the study.

PMID- 15724626
TI  - [The problem of health state assessment from the point of view of adaptational
      reactions theory].
AB  - Human health condition can be estimated only using adaptive responses theory. We
      include overactivation responses and incomplete adaptation in addition to stress
      reactions in the distress-group. Quiet and raised activation reactions were
      included into the eustress-group. All health spectrum should be divided in three
      groups. For health persons: 1) physiologic standard = safe health level =
      eustress reactions of high reactivity level 2) prenosological conditions =
      eustress reactions of low reactivity level, orientation, 3) premorbid conditions
      = adaptation mechanism breaking = distress reaction. For patients: 1) auspicious
      course of the disease = complete remission = eustress reactions of high
      reactivity level, 2) indefinite course of the disease = partial remission =
      eustress reactions of low reactivity level, orientation, 3) severe course of the
      disease = absence of remission = unfavorable prognosis = distress reaction.

PMID- 15724627
TI  - [Substantiation of studies in cerebral hemodynamics in orthostatic position
      during determination of occupational psychophysical preparedness of military
      personnel].
AB  - Military personnel of operations staff with no apparent healthy problems
      underwent Doppler ultrasound study to determine their cerebral hemodynamics.
      There were 60 studies. Each of the examined has been subjected to 6 Doppler
      ultrasound studies in recumbent and sitting position. The obtained results showed
      the position of a patient to have significant influence upon cerebral blood flow
      indices. It was proved that assessment of cerebral hemodynamics during
      determination of occupational psychophysical preparedness of military personnel
      operations staff should be carried out in sitting position.

PMID- 15724629
TI  - Percutaneous mitral commissurotomy: technique, results, and selection of
      patients.
AB  - Fifteen years of experience with percutaneous valve dilatation for mitral
      stenosis have shown the following: it is an effective treatment in a wide range
      of patients; its risk is low when it is performed by experienced teams, and more
      than 10 years follow-up demonstrates excellent durability of the procedure; the
      prediction of the immediate and long-term results is multifactorial and based on
      clinical and anatomic variables which should be taken into account when selecting
      the candidates for the procedure. Today balloon commissurotomy is a substitute
      for surgical commissurotomy and a complement to valve replacement.

PMID- 15724628
TI  - [History of formation and further functioning of hospital bases within Army
      Health System of Russia and USSR].
AB  - Nowadays Army Health System of Ukraine sees the formation of its quite new staff-
      organizational structure. Taking it into account, we would perform the
      reformation process of medical provision system of the army of Ukraine more
      effectively if we considered its experience of formation and functioning of
      medical provision system of military contingents of past wars and that of armed
      conflicts. Thus, the importance of history studying of past processes is that it
      allows using positive experience and avoiding negative one during the process of
      optimization.

PMID- 15724630
TI  - Timing of surgery in asymptomatic aortic stenosis.
AB  - Prospective studies have convincingly shown that sudden death in asymptomatic
      patients with AS is rare and prognosis is good as long as LV function, exercise
      tolerance and exercise hemodynamics remain normal. The time interval to
      development of LV dysfunction is not known. Therefore the initial evaluation
      should be confirmed after 3-6 months including echocardiography and exercise
      testing to identify patients with rapid progression, LV dysfunction and other
      high risk patients in whom surgery can be expected to improve prognosis even if
      the patient remains asymptomatic.

PMID- 15724631
TI  - New criteria for diagnosing infective endocarditis.

PMID- 15724632
TI  - Tricuspid regurgitation a benign disease?

PMID- 15724633
TI  - Management of patients with prosthetic heart valves during non-cardiac surgery.
AB  - Non-cardiac surgery in patients with prosthetic heart valves poses the particular
      hazards of infective endocarditis, increased bleeding risk and the possibility of
      acute/subacute valve thrombosis or systemic thromboembolism associated with
      interrupted anticoagulation. Management is complicated by the absence of
      randomised trials examining peri-operative anticoagulation management.
      Thromboembolic risk increases substantially when oral anticoagulation is
      discontinued and valve thrombosis may be inapparent for 1-2 months. This delayed
      diagnosis makes it difficult to identify the inciting event, either clinically or
      in experimental trials. Furthermore, the absence of early post-operative events
      may falsely suggest that peri-operative anticoagulation was safe and adequate.
      The approach to management therefore remains controversial. Seamless oral
      anticoagulation is preferred whenever possible and this is safe for a range of
      minor procedures, including cardiac catheterisation, dental and ophthalmic
      surgery. Major surgical procedures require withdrawal of oral anticoagulation
      before surgery to lower the international normalised ratio (INR) to <1.5 and
      maintained anticoagulation with unfractionated heparin which should be started
      when the INR is <2.5 in high risk patients and <2.0 in those at lower risk. The
      evidence to support the safety of low molecular weight heparins in this situation
      is scanty and despite its widespread promulgation this approach is NOT
      recommended. Oral anticoagulation is then resumed post-operatively, though
      therapeutic levels are not achieved for several days. The determination of which
      patients require prolonged overlap of heparin and oral anticoagulants is
      difficult. Clinical judgement is required but these regimes are strongly
      recommended for those at highest risk of thromboembolism. With strict adherence
      to these guidelines, the incidence of major complications is low.

PMID- 15724634
TI  - [Left ventricle TEI index--assessment of clinical role in patients with aortic
      valve stenosis].
AB  - AIM: The study aimed to assess the clinical efficacy of the TEI index in patients
      with aortic valve stenosis (AVS). METHODS: The study group comprised 30
      consecutive patients (12 F; 18 M; mean age: 60.1 +/- 9.2; range: 48-70 years)
      with aortic valve stenosis. Their clinical status was evaluated according to the
      NYHA criteria. A complete 2-dimensional, Doppler and color flow Doppler
      examination was performed. To assess systolic and diastolic left ventricle
      function we used ejection fraction--EF (%) and transmitral inflow velocity E/A
      ratio, respectively. The TEI index was calculated as (a - b)/b, were a is the
      interval between the cessation and onset of mitral inflow, and b is the ejection
      time. We also determined: maximal transaortic gradient--Ao max gr (mmHg), aortic
      valve area--AVA (cm2) and left ventricular mass index--LV mass index (g/m2).
      Based on clinical symptoms we divided patients into two groups: Group 1 (NYHA
      I/II) and Group 2 (NYHA III and IV). RESULTS: There were no significant
      differences in age, Ao max gr, AVA, EF and ejection time (b) between groups. But
      we found significantly prolonged time interval (a) and consequently significantly
      higher TEI index (p<0.001) in the group with severe symptoms. LV mass index and
      E/A ratio were also related to the patient's clinical status (p<0.05) but the TEI
      index seems to be more sensitive in distinguishing severely limited patients.
      CONCLUSION: The TEI index revealed to be closely related to symptoms in patients
      with aortic valve stenosis. The patient's clinical status seems to depend more on
      the TEI than on the conventional measured parameters like aortic valve area and
      transaortic gradient.

PMID- 15724635
TI  - [Intravascular ultrasound imaging and histological evaluation of the aorta].
AB  - It has been shown in several in-vitro studies that IVUS images correlate well
      with histology and angioscopy. The existing data on intravascular imaging of
      large-diameter elastic arteries are scant. The aim of this study was to compare
      the IVUS images of aorta with the reference method--histological section by
      evaluating the accuracy of measurements performed at corresponding aortic
      segments. MATERIALS AND METHODS: 15 human aortic specimens were derived from post
      mortem examination and in-vitro IVUS imaging was performed, including
      measurements of vessel diameters and cross-sectional areas in three specified
      areas. Corresponding regions of interest obtained with histology were
      subsequently evaluated and parameters matched to those by IVUS were calculated.
      RESULTS: Total of 45 pairs of measurement were compared. Mean vessel internal
      diameter on IVUS was 14.4 mm (SD 2.7 mm) and intima thickness was 0.6 mm (SD 0.8
      mm). The corresponding aortic internal diameter observed with histology was 13.2
      (SD 2.6 mm) and intima thickness--0.3 mm (SD 0.03). An overall agreement between
      IVUS and histology specimens was high, yelling correlation ratio of 0.99. The
      highest level of agreement was observed for external vessel area validation-
      correlation ratio 0.98. The largest discrepancy was observed for intima and media
      thickness, with correlation ratios of 0.61 and 0.72, respectively. CONCLUSIONS:
      Our data suggest that examination of aorta with intravascular ultrasound is
      feasible and may provide additional information in assessment of cardiovascular
      pathology. More complete risk stratification, which includes IVUS examination of
      aorta, is an important factor to determine the necessity for early preventive
      treatment, especially in patients with normal coronary arteries.

PMID- 15724636
TI  - [Regional aortic function studied by three-dimensional echocardiography].
AB  - Aortic pulsation is caused by the arterial blood pressure variation during the
      cardiac cycle. Thickening of arterial intima, as well as the presence of
      atherosclerotic plaques may influence vessel pulsation by increasing wall
      stiffness. There is no data available concerning regional changes in aortic
      elasticity in relation with local wall thickness and the magnitude of
      atherosclerosis. The study group comprised 36 patients (27 men, 9 women, mean age
      53 +/- 10 years) referred to our echocardiographic laboratory for transesophageal
      echocardiography (TEE). TEE probe was placed at the depth of 35 cm. The spatial
      interval between acquired images was 3 degrees. The reconstructed data sets were
      reviewed and the border between the aortic wall, plaque and lumen was determined.
      The reconstruction of a two-centimeter-long segment of aorta was divided by
      coaxial planes into four longitudinal sections. Thereafter the diastolic and
      systolic radius of each section, thickness of atherosclerotic plaques and intima
      media thickness in each section were measured. The regional beta-index was
      calculated as Ln (systolic pressure/diastolic pressure)/relative change in
      regional aortic lumen, where relative change in regional aortic lumen was
      calculated as the difference between aortic lumen volume in systole and diastole
      divided by aortic lumen volume in diastole. In total, 144 aortic sections were
      analyzed. The volume of two-centimeter-long segments of descending aorta ranged
      from 6.9 cm3 to 31.5 cm3 (mean 12.8 +/- 5.2 cm3) in systole and from 4.9 cm3 to
      29.2 cm3 (mean 11.2 +/- 4.9 cm3) in diastole. The volume of the examined sections
      of the aortic segments ranged from 1.3 cm3 to 10.6 cm3 (mean 3.2 +/- 2.6 cm3) in
      systole and from 1.1 cm3 to 8.7 cm3 (mean 2.8 +/- 1.5 cm3) in diastole. The
      pulsation of the aortic sections varied from 0.01 cm3 to 2.7 cm3 (mean 0.4 +/-
      0.3 cm3), which constituted 0 to 37% (mean 13 +/- 8%) of the section volume. The
      thickness of atherosclerotic plaques in the studied aortic sections ranged from
      0.0 mm to 1.1 mm (mean 0.3 +/- 0.2 mm) and the intima-media thickness was within
      the range 1.3 mm to 2.5 mm (mean 1.9 +/- 0.3 mm). The regional beta-index of the
      individual section ranged from 1.1 to 253.9 (mean 9.3 +/- 24.3). The regional
      beta-index was statistically significantly dependent on the intima-media
      thickness (p=0.02). We found no significant correlation between beta-index and
      the thickness of atherosclerotic plaques in the studied segments (p=0.38).
      CONCLUSIONS: Transoesophageal three-dimensional echocardiography facilitates
      quantitative analysis of aortic wall stiffness and regional beta-index
      measurements. The local variability of beta-index is correlated with intima-media
      thickness, whereas the correlation with the thickness of atherosclerotic plaques
      is not statistically significant. These measurements may be of importance in the
      assessment of the degree of atherosclerosis advancement. It forms new
      perspectives in diagnostics with the ability to evaluate the influence of
      pharmacotherapy and life-style modifications.

PMID- 15724637
TI  - [Ultrasound stethoscope in the rapid assessment of left ventricular systolic
      function and valvular regurgitation--personal experience].
AB  - BACKGROUND: Recent technological advances enabled miniaturization of
      echocardiographic machines and construction of portable "ultrasound
      stethoscopes", which enable rapid two-dimensional and color-Doppler imaging and
      supplement clinical examination of the heart. We present the results of
      systematic assessment of these devices in comparison with standard
      echocardiographic machines. METHODS: We prospectively examined with both
      ultrasound stethoscopes and standard echocardiographic machines 60 patients
      referred to our laboratory for routine echocardiographic examination. Image
      quality (score: 1 to 4; best to worst), accuracy in qualitative evaluation of
      valvular regurgitation and left ventricular function (ejection fraction) were
      directly compared. Color Doppler assessment of valvular regurgitation was graded
      on a standard four point scale. A two or more point difference was considered
      major. Ejection fraction was estimated (the ultrasound stethoscope is not
      equipped with appropriate software). RESULTS: Image quality was significantly
      worse in the case of ultrasound stethoscope (2.6 vs 2.1; p<0.0001). Major
      differences in the assessment of regurgitant jets were present in 3 cases (5%) (1
      mitral and 2 tricuspid). The degree of agreement was good in the case of mitral
      and pulmonary regurgitation (kappa=0.61 and 0.74 respectively), very good in the
      case of aortic regurgitation (kappa=0.80) and moderate in the case of tricuspid
      regurgitation (kappa=0.48). The differences in the assessment of aortic and
      mitral regurgitant jets correlated with the image quality (p<0.05). A Bland
      Altman graph comparing the results of ejection fraction assessment revealed good
      agreement between methods. CONCLUSIONS: Results of the systematic evaluation of
      the use of ultrasound stethoscopes in the rapid evaluation of left ventricular
      systolic function and valvular regurgitation. Although image quality achieved
      with the hand-held stethoscope was worse, nevertheless it was adequate for the
      purpose of performing rapid limited assessment of cardiac and valvular function.

PMID- 15724638
TI  - [Use of coronary artery multislice spiral computed tomography (MSCT) to identify
      patients for surgical revascularisation].
AB  - Conventional coronary angiography is the undisputed gold standard for the
      detection of coronary artery disease. A small but not negligible risk related to
      the procedure, cost, and radiation exposure have given rise to the development of
      noninvasive alternatives such as multi-slice computed tomography, and magnetic
      resonance coronary angiography. In some patients classic X-ray coronary
      angiography involves high risk and technical difficulties. Fast, non-complicated
      and easy to use non-invasive imaging procedures should be developed to avoid
      unnecessary or technically difficult, uncomfortable situations for patients with
      documented myocardial ischemia. We present three cases of patients who underwent
      coronary artery bypass graft surgery or were disqualified from it on the basis of
      MSCT imaging.

PMID- 15724639
TI  - [Low ejection fraction as risk factor after aortic valve replacement].
AB  - The aim of the study is to estimate the operative risk of aortic valve
      replacement for severe aortic valve stenosis in patients with distinctly impaired
      left ventricular function (ejection fraction below 40%). From the population of
      2512 pts, who underwent aortic valve replacement in the years 1990 to 1999
      because of acquired malformation, a group of 108 pts (4.3%), fulfilling the above
      mentioned conditions was selected. Between them prevailed men, 92 (85.2%), and
      the average age was 53.4 +/- 14.5. All pts remained in the NYHA functional class
      III/IV. The average ejection fraction was estimated 28.2 +/- 14.3%. The pts
      demonstrated concentric left ventricular hypertrophy, severe aortic valve
      calcifications, the average valvular area was 0.91 cm2, and the pressure gradient
      over the valve was 71 +/- 44 mmHg. The pts were operated on by different surgeons
      but after the same protocol of extracorporeal circulation and cardioplegia
      administration. Low output syndrome occurred in ca 40% of pts, and cardiac
      failure was the main cause of death. The hospital mortality was 8.6%, and it was
      over two times higher then the whole population of pts, who underwent aortic
      valve replacement. All survivors (91.4%) demonstrated clinical improvement
      already during the early observation. CONCLUSIONS: Low ejection fraction is an
      important risk factor of surgery for aortic valve stenosis. However, the elevated
      operative mortality, comparable to other institutions, may be accepted taking for
      consideration, that surgery is the only way of treatment and improvement may be
      expected in about 90% of pts, including anatomical and hemodynamic parameters, as
      well as life longevity and comfort. In the extreme cases the HTX should be
      considered.

PMID- 15724641
TI  - [Significant aortic valve stenosis in the prenatal period--diagnosis, treatment,
      outcome. Two-center study].
AB  - OBJECTIVE: Retrospective analysis of the spectrum of fetal aortic valve stenosis
      with completed neonatal follow-up. METHODS: Fetal echocardiograms of 12 fetuses
      with aortic stenosis (AS) were analyzed. Mean gestational age at the time of
      diagnosis was 29.6 weeks. RESULTS: In all 12 cases critical AS has been detected.
      The left ventricle was estimated as small in three cases, in 7 cases as enlarged
      and hypokinetic LV (SF<28%) and in the next two cases the LV was well formed. In
      6 AS cases, endocardial fibro-elastosis has been detected. Six fetuses presented
      mitral valve insufficiency; in three cases small LV mitral valve stenosis was
      diagnosed. Cardiomegaly occurred in 7 cases, including 5 cases with HA/CA > 0.5.
      Hypoplastic aorta has been detected in 2 cases and in one coarctation of the
      aorta. Retrograde flow in aortic arch and poor left ventricular function was
      diagnosed in ten cases. In 2 fetuses extracardiac malformations were present:
      hydrocephalus and pylorostenosis. In 83% of the cases CS had been performed and
      17% were delivered vaginally (2 intrauterine fetal deaths). Four neonates had
      been qualified to percutaneous balloon valvuloplasty, in three cardiac surgery
      had been performed. Three neonates with AS (25%) survived--two after
      valvuloplasty (one of them required also cardiac surgery) and one after Norwood
      procedure. CONCLUSIONS: 1. Poor prognostic factors for neonates with critical
      fetal AS were as follows: small LV, retrograde flow in aortic arch, poor left
      ventricular function and presence of extracardiac anomalies. 2. Neonates who
      survived with fetal SA, had isolated CHD and well formed LV (also with
      endocardial fibroelastosis).

PMID- 15724642
TI  - [Parachute mitral valve coexisting with complex congenital heart defect.
      Successful multistage surgical treatment].
AB  - Type parachute valve is a very rare bicuspid valve congenital anomaly. When signs
      of dysfunction are noted the valve has to be replaced with an artificial one. The
      case describes a 7-year old girl suffering from complex congenital heart defect:
      coarctation of the aorta followed by hypoplastic aortic arch, ventricular septal
      defect and parachute mitral valve. In the neonatal period the girl had been
      operated on by the subclavian floppy aortoplasty method due to coarctation of the
      aorta. At the age of 2, another surgical correction was performed: ventricular
      sept defect closure simultaneously with mitral valvuloplasty. In infancy she
      failed to thrive, also signs of heart failure had been observed which resulted
      from increasing mitral valve stenosis and III grade mitral insufficiency. These
      findings in with artificial valve replacement (type Sorin O 23 mm). Procedure has
      been performed by the left atrium. Post operational period was uneventful. Proper
      function of the implanted valve has been observed with no perivalvular leakage
      and left atrium diameter has been normalized.

PMID- 15724640
TI  - Indications for reoperation for valvular prosthesis dysfunction in urgent and
      elective patients.
AB  - OBJECTIVES: Comparison analysis of indications for operation, early clinical
      outcomes and hospital mortality between patients reoperated for valvular
      prosthesis dysfunction urgently and electively. MATERIAL AND METHODS:
      Retrospective data analysis of 94 patients (pts) reoperated for valve prosthesis
      dysfunction at Department of Cardiovascular Surgery and Transplantology in
      Krakow, Poland between January 1999 and December 2002. RESULTS: Valvular
      reoperation was elective procedure in 69 pts (73.4%)--group A: 46 males (M), 23
      females (F), age 23-71 (av. 51.31 +/- 10.2). Urgent operation was performed in 25
      pts--group B: 17 M, 8 F, age 29-77 years (av. 5.41 +/- 13.26). In group B: 9
      patients underwent reoperation for dysfunction of aortic valve (2 allogenic, 7
      mechanical), 13 pts for mitral valve dysfunction and 3 pts for both aortic and
      mitral valve dysfunction. In group A: 24 pts for mitral valve dysfunction, 37 pts
      for aortic valve dysfunction (25 allogenic, 12 mechanical) and 8 pts for both
      aortic and mitral valve dysfunction. In group B: 16 pts (64%) were operated in
      NYHA class IV; 8 in cardiogenic shock; on which 8 pts with active endocarditis, 3
      pts with sepsis and 1 patient in septic shock. Average operative risk calculated
      as Euroscore was 30.86 in group B and 13.15 in group A (p<0.05). Overall hospital
      mortality was 12.6% (12 pts). In group B: 7 pts died (28%), 3 pts due to
      multiorgan failure, 1 patient due to sepsis, 2 pts due to aorta rupture and 1 due
      to left ventricle rupture during cardiopulmonary rescuscitation. In group B 5 pts
      died (7.2%). CONCLUSION: Patients reoperated urgently for valve prosthesis
      dysfunction were in worse preoperative state, had significantly higher
      preoperative risk and in hospital mortality than patients reoperated electively.

PMID- 15724643
TI  - [Use of cardiovascular magnetic resonance (CMR) in preoperative assessment of
      aortic stenosis--case report].
AB  - PURPOSE: CMR is a helpful additional diagnostic method in cardiac imaging. Thanks
      to high spatial and temporal resolution and high quality of obtained images this
      method is used in patients with poor echocardiographic acoustic window. We
      present a case of a patient, in whom CMR was conclusive as a non-invasive method
      of aortic valve stenosis assessment before qualification to cardiosurgery.
      METHODS: CMR was performed in a 70-year-old female A. C. who was under
      cardiological control due to symptomatic aortic stenosis. Because of difficulties
      in echocardiographic examinations (TTE) the aortic valve area was impossible to
      evaluate and aortic gradient value was difficult to assess and it differed in
      consecutive TTE performed over a short period (maximal gradient: 66-91 mmHg; mean
      gradient: 37-50 mmHg). The patient underwent CMR (Magnetom Vision Plus 1.5 T,
      Siemens) with the use of cine gradient echo sequences which made possible
      morphological and functional assessment of the valve and left ventricle. LV mass
      indices, IVS thickness, EF, aortic valve area, maximal aortic valve gradient were
      measured. RESULTS: CMR revealed: left ventricle muscle hypertrophy (IVS--1.8 cm;
      LV mass index--210 g/m2), EF--70%, no regional contractility disturbances and
      aortic valve area less than 1 cm2. In aortic valve and anulus extensive
      calcifications were visualised as low intensity signal area. Turbulent flow
      through aortic valve was found, maximal gradient about 64 mmHg. On the basis of
      all clinical symptoms and measurements based on imaging methods, the patient was
      qualified for cardiosurgery which was held in the Department of Cardiovascular
      Surgery and Transplantology. Coronary angiography revealed no significant
      stenosis. The operation was performed in extracorporeal circulation, general
      hypothermia and cardioplegia. Calcified aortic valve leaflets were excised and
      replaced by artificial valve (St. Jude Medical 21A Masters). The patient is in
      good health and was discharged. CONCLUSIONS: CMR is a valuable non invasive
      imaging method complementary to TTE in morphological and functional assessment of
      aortic valve and left ventricle, especially in patients with poor acoustic window
      in TTE.

PMID- 15724644
TI  - [Favorable reverse remodelling of the left ventricle in elderly patients
      following aortic valve replacement].
AB  - Progress of surgical technique and anaesthesia enabled aortic valve replacement
      in the very elderly patients. However both valvular heart disease and ageing are
      associated with myocardial fibrosis. It is not known whether reverse remodelling
      and regression of hypertrophy, observed in the young patients after aortic valve
      surgery is possible also in the elderly. The aim of the study was to evaluate the
      changes of left ventricular structure and function in the elderly patients
      subjected to aortic valve replacement for aortic stenosis. Echocardiographic
      examinations were performed prior to surgery, approximately 4 weeks after the
      procedure and after an average of 32 months of follow-up. Left ventricular end
      systolic (LVESV) and end-diastolic volumes (LVEDV) and ejection fraction (LVEF)
      were measured, as well as interventricular septum (IVSD) and posterior wall
      thickness (PWD). 43 patients over 74 years old (range 74-83), with aortic
      stenosis and transvalvular aortic gradient of 60-150 mmHg (mean 104 mm Hg), were
      included in the analysis. 17 patients received biological and 26 mechanical
      prosthesis. During the long term follow up LVEDV decreased from 143 ml to 114 ml,
      LVESV from 59 ml to 36 ml and EF increased from 59% to 68% (all p<0.05).
      Significant regression of left ventricular wall hypertrophy was observed (IVSD
      from 1.53 cm to 1.32 cm and PWD from 1.4 cm to 1.28 cm, all p<0.05). IN
      CONCLUSION: the improvement of physical efficiency were observed. Favorable
      reverse remodelling of the left ventricle is observed also in elderly patients
      following valve replacement.

PMID- 15724645
TI  - [Calcific and degenerative aortic stenosis--pathogenesis and new possibilities of
      treatment].
AB  - Currently, degenerative changes are the most important cause of valvular aortic
      stenosis. Epidemiological as well as experimental studies suggest that
      inflammatory process induced and intensified by common atherosclerosis risk
      factors as age, hyperlipidemia, diabetes, hypertension, male sex and smoking, is
      responsible for these changes. Microscopic examination of the affected valves
      reveals: endothelium derangement, thickening of the subendothelial layer, intra-
      and extracellular lipid, lipoprotein and protein deposits, inflammatory
      infiltrate composed of macrophages, T lymphocytes, foam cells and intensive
      calcification in the zones of lipid accumulation. The method of choice in the
      assessment of aortic valve stenosis is echocardiography. New, more sensitive,
      quantitative radiological methods like Electron Beam Computed Tomography and
      Multislice Computed Tomography may be useful in a detection of early lesions and
      monitoring of their progress. As the process of aortic valve degeneration is long
      and progressive in nature, early introduction of effective prevention would
      decrease the number of patients operated on for aortic stenosis. A number of
      studies indicate the role of statins in slowing the progression of aortic valve
      degeneration. Nevertheless, no large randomized prospective study has emerged in
      this field and there is no strong enough evidence for the efficacy of statins in
      degenerative aortic valve disease.

PMID- 15724646
TI  - [Evaluation of the correlation between calcifications in the aortic valve and in
      the coronary arteries using MSCT].
AB  - INTRODUCTION: Calcium score is the subject of wide research in evaluating
      atherosclerotic progression. The study aimed to determine whether an association
      exists between the presence of aortic valve calcium (a-CS) and coronary calcium
      (ca-CS) in patients with aortic valve stenosis as detected by multislice computed
      tomography (MSCT). METHOD: We examined 45 patients (27M; 18F); aged 67 (SD 9.5)
      with the aortic valve stenosis mean grad. 47.8 mmHg; max. grad. 75.3 mmHg; mean
      aortic valve area 1.02 cm2. The quantitative evaluation of calcifications on the
      aortic valve (a-CS) and in the coronary arteries (ca-CS) was performed in all
      patients with the use of MSCT and conventional coronary angiography (CCA). Aortic
      valve and total coronary artery calcium score were analysed. U-Mann-Whitney test
      and Pearson's correlation were used in the statistical analysis. The correlation
      coefficients between a-CS and ca-CS and between the lesions in coronarography and
      ca-CS were calculated. RESULTS: There was a weak correlation between aortic valve
      calcifications and coronary artery calcifications p=0.05, r=0.1. In 18 patients
      no coronary calcifications were found, none of the patients had lesions in CCA.
      In all patients with ca-CS > 400 there were significant stenoses in coronary
      arteries. A correlation between significant stenoses in CCA and ca-CS was
      established (p<0.01). CONCLUSIONS: Aortic valve calcium score (a-CS) may indicate
      the advancement of coronary artery calcifications in the patients with aortic
      valve stenosis. In this particular group ca-CS correlates well with stenoses in
      coronary arteries, as identified by CCA. Patients with the ca-CS > 400 are at
      high risk of coronary arteries stenoses, which is significant information in
      operation procedure qualification and time to surgery.

PMID- 15724647
TI  - [Effect of the dispersion of calcium deposits on allogenic aortic valves
      durability. Mineralization phases].
AB  - This investigation was aimed at comparison of calcium content and calcium
      dispersion in allogenic aortic valve leaflets removed due to dysfunction, to
      establish the influence of both parameters on graft durability. Calcification was
      assessed histochemically (von Kossa) as well as physicochemically using atomic
      absorption spectroscopy (AAS). The morpho-metric data (leaflet area involved in
      the calcification process) were obtained by computer-assisted image analysis
      system. The dry weight content of leaflet calcium and phosphorus were assessed by
      atomic absorptive spectroscopy (AAS) and Ca/P ratio was calculated. Calcium
      dispersion coefficient (Dc) was established according to the formula: Dc =
      1/Ca(c)/Ap, where Ca(c) = calcium dry weight concentration; Ap = percent of
      leaflet area involved in calcification. We found biphasic correlation between
      calcium concentration and area involved in calcification. The first one was
      characterized by rising dispersion of calcium deposits while for the second one
      saturation with hydroxyapatite of formerly calcified areas was predominant,
      negatively influencing graft durability. Allograft durability was correlated with
      calcium dispersion (Dc) (p<0.001), while no significant correlation was found
      with calcium concentration. Decreased Dc was characteristic for 93.8% of low
      durability grafts (<11.6 years). Our results suggest that lowered calcium
      dispersion decreasing allograft lifetime and is a better predictor of allograft
      durability than the total calcium content.

PMID- 15724648
TI  - [Mineralization of homograft aortic valves stored in a nutrient solution].
AB  - BACKGROUND AND AIM OF THE STUDY: Mineralization of the homograft aortic valve
      cusps is a complex process leading to their degeneration and decreasing
      durability. Factors that play a decisive role in regulation of mineralization,
      growth of hydroxyapatite crystals are still open questions. We studied
      development of mineralization in the homograft aortic valves prepared for
      transplantation stored in the Parker's solution with antibiotics. METHOD: The
      aortic valves were explanted from 12 donors <18 hours after death. All the cusps
      were divided into halves. One half of each cusp was stored in the Parker's
      solution with antibiotics for 28 days at 4 degrees C. Concentrations of several
      elements (P, S, Cl, K, Ca, Mn, Fe, Ni, Cu, Zn i Sr) in incubated and control
      samples were determined using energy dispersive X-ray fluorescence (ED-XRF).
      RESULTS: The study showed that the concentration of Ca and Ca/P increased during
      incubation that may indicate development of mineralization. CONCLUSIONS: The
      homograft aortic valve cusps underwent mineralization during in vitro incubation.
      This may aggravate mineralization in the aortic valve recipients and decrease
      valve durability which indicate a need for modification of storing condition.

PMID- 15724649
TI  - [Which echocardiographically unrecognised complications of native aortic valve
      endocarditis may be found during operation?].
AB  - The aim of the study was to determine the type and localisation of complications
      of aortic valve endocarditis, that have not been recognised on transthoracic
      (TTE) and/or transesophageal (TEE) echocardiographic study. The echocardiographic
      findings were retrospectively compared and contrasted with direct surgical
      inspection in 156 consecutive adults operated on native aortic valve endocarditis
      in our institute during the last 8 years. We analysed recognition of abscess,
      pseudoaneurysm, fistula and cusp rupture. Periannular complications were detected
      at operation in 51 pts, cusp rupture in 97 pts. Sensitivity of TTE in recognition
      of abscesses was 55%, TEE--60%; pseudoaneurysm--TTE--64%, TEE--100%; fistula--TTE
      60%, TEE 100%; cusp rupture--TTE 65%, TEE 81%. Both echocardiographic methods
      have some inherent limitations while diagnosing complications of aortic valve
      endocarditis. In particular, these include small abscesses and cusp rupture.
      Using both modalities in a complementary way seems to offer the best approach in
      overall definition of the extent of inflammation.

PMID- 15724650
TI  - [Early results of surgical treatment in acquired heart diseases during
      endocarditis in own material].
AB  - BACKGROUND: Endocarditis can concern natural as well as artificial heart valves.
      In conservative treatment mortality reaches 24-60%. Surgical procedure is the
      only way to save these patients in most cases. METHODS: Between 1998-2001, 114
      patients underwent surgery because of valve endocarditis, 86 male and 28 female.
      43 patients underwent mitral valve replacement (MVR), (13 MV reoperation), 51
      aortic valve replacement (AVR), (16 AV reoperation) and 20 patients underwent MVR
      and AVR (3 both valves replacement). Three groups were similar regarding age,
      gender, emergency or elective procedures and NYHA class four. All patients
      underwent open heart surgery in ECC with hypothermia and crystalloid cardioplegia
      done by the same group of surgeons. RESULTS: Operative mortality in the MVR group
      was 11.6% (five of 43) compared to 3.9% (two of 51) AVR patients and 25% (five of
      20) MVR and AVR group. The highest mortality rate was in both infected artificial
      valves procedures. There was growth of the bacteria in intraoperative material in
      37.6% (33) of cases, mainly Staphylococcus epidermidis and Staphylococcus aureus.
      Incidence of postoperative sepsis, multiorgan failure, high grade atrio
      ventricular block or low cardiac output was the highest in MVR and AVR patients.
      Independent predictors of operative mortality included increasing patient age,
      female gender, infected valve reoperation, and history of stroke. CONCLUSIONS:
      Our study suggests that patients with endocarditis and compromised hemodynamic
      status can be operated with acceptable morbidity and mortality. If
      echocardiography shows the cuspids perforations or vegetations, chords tendinous
      rupture or perivalvular leak, the patients should undergo cardiac surgery as soon
      as possible, in order to avoid severe embolic complications.

PMID- 15724651
TI  - Dysfunction of primary aortic valve prosthesis--allogenic versus mechanical-
      preoperative differences.
AB  - OBJECTIVES: Comparison of preoperative characteristics between patients
      reoperated for allogenic and mechanical aortic valve prosthesis dysfunction.
      METHODS: Retrospective data analysis of 47 patients reoperated for aortic valve
      prosthesis dysfunction at Department of Cardiovascular Surgery and
      Transplantology in Krakow, Poland between January 1999 and December 2002.
      RESULTS: In analyzed group 27 patients were operated for dysfunction of allogenic
      valve (Gr. A), 20 pts for mechanical valve (Gr. B). Group A: 21 males (M), 6
      females (F), age 23-68 years old (av. 47.10 +/- 11.71); Group B: 18 M, 2 F, age
      38-77 (av. 54.73 +/- 11.03), p<0.05. Time between operations in group A was 69
      258 months (av. 164.34 +/- 66.02) months and in group B 0.5-348 months (av. 77.27
      +/- 98.29) p<0.01. In group A, 5 pts and in group B, 7 pts were in NYHA group IV
      preoperatively. Echocardiography revealed that diastolic left ventricular
      dimension (LVDD) was larger in group A: av. 6.7 cm and 5.36 cm in group B,
      p<0.05. 2 pts from group A and 7 pts from group B were operated urgently
      (p<0.05), including 3 pts with aortic dissection. Definite infective endocarditis
      was diagnosed in 6 pts from group A and 11 pts from group B, p<0.05. In group A,
      1 patient was urgently operated for infective endocarditis with vegetations, he
      died due to multiorgan failure. In group B, 6 pts died including all 3 with
      aortic dissection. CONCLUSIONS: Patients reoperated for allogenic aortic valve
      prosthesis dysfunction are: younger, reoperated after a much longer period of
      time with slower valve dysfunction progress (larger LVDD), most frequently
      reoperated electively, less frequently with endocarditis as the cause of valve
      dysfunction than in patients reoperated for mechanical aortic valve dysfunction.

PMID- 15724652
TI  - [Quality of life after homograft aortic valve replacement and reoperation].
AB  - AIM: To evaluate quality of life (QoL) in patients after aortic homograft
      implantation for aortic valve disease and in those who had undergone reoperation
      due to homograft dysfunction. METHODS: QoL was assessed in 354 patients (72 women
      and 282 men, mean age 55.1 +/- 11.5 years, range 13-69) after aortic homograft
      implantation. Patients were divided into two groups: I--patients after aortic
      homograft implantation without reoperation (291 patients) and II--patients after
      reoperation (68 patients). We used two questionnaires: SF 36 (Short Formulation
      36) and a self-developed questionnaire for patients after cardiac operation
      (SDQ). SF 36 has three levels: a) 36 items; b) eight scales: physical activity,
      social activity, limitations in every day activity, body pain, mental health,
      emotional problems, vitality and health perception; c) two summary measures that
      aggregate scales; general physical health which constitutes of physical activity,
      limitations in every day activities, body pain, health perception and general
      mental health which constitutes the rest of four scales: social activity, mental
      health, emotional problems, vitality. Each scale is standardized from 1 to 100
      with > 50 indicating better than general population average. SDQ is focused on
      social and demographic factors, clinical symptoms before and after operation,
      risk factors and physical and occupational activity. RESULTS: By SF 36, only
      health perception was below general population average. We found a statistically
      positive relationship between QoL and high physical and occupational activity in
      both groups (p<0.05). The presence of dyspnea, chest pain, palpitations, edema,
      faints, fear/anxiety and hypertension were related to decreased general physical
      and mental health in both groups (p<0.05). CONCLUSIONS: Patients after aortic
      homograft implantation have high QoL. This holds also for those after reoperation
      for homograft dysfunction. Symptomatic patients have lower QoL. Higher QoL is
      associated with physical and occupational activity. There is no difference in
      general physical health in both groups. General mental health is decreased in
      reoperated patients. Since reoperated patients more often suffer from emotional
      problems, they may particularly benefit from the psychological support.

PMID- 15724654
TI  - [Early haemodynamic changes after transcatheter closure of atrial septal defect].
AB  - OBJECTIVE: To evaluate the outcomes of transcatheter closure of secundum atrial
      septal defect (ASD) using the Amplatzer Septal Occluder (ASO). METHODS: Between
      December 2000 and December 2002, 27 adult patients (20 females, 7 males) with a
      mean age of 41.1 +/- 13.3 (range 18-62) years were enrolled for an attempt at ASD
      closure with the ASO device. All patients had an isolated secundum ASD with a
      large left-to-right shunt (ratio of pulmonary to systemic blood flow or Qp:Qs
      >1.5:1). Transthoracic color Doppler echocardiographic examination was performed
      on all patients before procedure, 24 hours, 1 and 6 months after surgery.
      Clinical observation (NYHA class) was performed 1 and 6 months after surgery.
      RESULTS: The ASO device was successfully implanted in all patients (procedure
      time 19-63 minutes, median 43 minutes, fluoroscopy time 4-40 minutes, median 12.6
      minutes), with only 3 patients with a trivial residual shunt. The defect echo
      diameter was 14.2 +/- 4.3 (7-24). At one month of follow-up transthoracic
      echocardiography showed that the device was correctly positioned in all cases and
      no predictors for a residual shunt were identified. Residual trivial shunt in one
      month follow-up was shaded in 3 patients. Paradoxical septal motion abnormalities
      normalized in all patients. The right ventricular dimension evaluated by 2D
      echocardiography decreased in 20 pts (74.1%), mean 5.0 +/- 3.4 mm (range 1.5-8),
      the right atrium dimension decreased in 21 pts (77.8%), mean 8.65 +/- 4.3 mm
      (range 2-20) and the left atrium dimension decreased in 15 pts (55.6%), mean 6.36
      +/- 3 mm (range 2-21). We didn't find correlations between ratio of left-to-right
      shunt before ASD closure and the decrease of right heart dimension as well as the
      decrease of pulmonary artery systolic pressure. CONCLUSIONS: Transcatheter
      closure of secundum ASD using the ASO is a safe and effective procedure, with
      excellent short-term follow-up results. During one month observation it caused
      partial normalization of echocardiographic parameters.

PMID- 15724653
TI  - [Atrial septal defect associated with mitral valve prolapse--prevalence and
      clinical significance].
AB  - AIM: High incidence of mitral valve prolapse (MVP) associated with atrial septal
      defect (ASD) has been reported. The study aimed to evaluate the prevalence,
      etiology and clinical significance of MVP in patients with ASD. METHODS: Forty
      seven consecutive patients with secundum type ASD (30 F; 17 M; mean age: 37.9 +/-
      14.0; range: 16-62 years) were enrolled into the study. All patients underwent M
      mode and two dimensional echocardiography to check for MVP, defined as the
      superior systolic displacement of mitral leaflets > or = 2 mm above annulus with
      coaptation point at, or superior to the annular plane. Pulmonary to systemic flow
      ratio (Qp/Qs), diastolic right ventricle dimension (RV), left ventricle dimension
      (LV) and left to right ventricle ratio (LV/RV) were measured. Furthermore, mitral
      and tricuspid valve insufficiency and right ventricle systolic pressure (RVSP)
      were evaluated. A symptom-limited, incremental exercise test (CPX)--modo Bruce on
      Marquette 2000 Treadmill was performed in every patient. We determined: time of
      exercise--Time (min), peak oxygen uptake--VO2peak (ml/kg/min), VO2peak expressed
      as % of predicted value--VO2% and anaerobic threshold--AT (expressed as % VO2
      max). The study population was divided into two groups: Group I--patients with
      ASD and MVP and Group II--patients with ASD without MVP. RESULTS: MVP was
      recognized in 17 patients (36%); anterior MVP was found in 14, two cases revealed
      posterior MVP and one was diagnosed with both anterior and posterior MVP. MVP was
      not associated with significant mitral regurgitation. Echocardiographic and CPX
      data are summarized in table I. There were no significant differences in age,
      RVSP, RV and LV diastolic dimensions between groups, although Qp/Qs was
      significantly higher (p=0.01) and LV/RV significantly lower (p=0.02) in the MVP
      group. Moreover, there was a significant negative correlation between Qp/Qs and
      LV/RV ratio (r=-0.70; p<0.001) in a study group. No significant difference in
      time of exercise, VO2peak, VO2%, and AT was observed between respective groups.
      CONCLUSIONS: Our data support the thesis that MVP associated with secundum ASD is
      a functional disorder due to the atrial shunt and leftward shift of
      interventricular septum. MVP does not affect cardiopulmonary capacity in ASD
      patients.

PMID- 15724655
TI  - [Early results of atrial septal defect closure with the Amplatzer Septal Occluder
      are impacted by tricuspid insufficiency].
AB  - OBJECTIVE: Our study reports the results of a comparison of transcatheter closure
      of secundum atrial septal defect (ASD) using the Amplatzer Septal Occluder (ASO)
      in patients with and without tricuspid insufficiency. METHODS: Consecutive 27
      adult patients (20 females, 7 males) with a mean age of 41.1 +/- 13.3 (range 18
      62) years having an ASD II and a transcatheter closure between December 2000 and
      December 2002 were analyzed. All the patients had an isolated secundum ASD with a
      significant left-to-right shunt (ratio of pulmonary to systemic blood flow or
      Qp:Qs >1.5:1). Patients were divided in two groups: group I--without tricuspid
      abnormalities (8 patients, 29.6%), group II--patients with tricuspid
      insufficiency I-III stage, (19 patients, 70.4%). Transthoracic color Doppler
      echocardiographic study was performed in all patients before discharge and was
      repeated one month after discharge. RESULTS: The mean age, the diameter of
      defect, the degree of left-to-right shunt, the diameter of implanted device were
      comparable in both groups. Before implantation the dimension of right heart
      cavities differed between groups. The right ventricular dimension was larger in
      group II (mean 36.2 mm vs. 29.1 mm; p<0.009), the right atrium diameter was
      larger in group II (46.2 mm vs. 24.3 mm; p<0.007). Pulmonary artery systolic
      pressure before the procedure was higher in group II (36.6 mmHg vs. 20.43 mmHg;
      p<0.006). The ASO device was successfully implanted in all the patients. At one
      month follow-up septal motion abnormalities normalized in all patients in both
      groups. The mean decrease of right atrium diameter in group I was 6.2 mm (range
      1.5-12 mm) compared to 9.6 mm (range 2-20) in group II, (p<0.001), the mean
      decrease of right ventricular diameter in group I was 5.8 mm (range 2-8 mm)
      compared to 3.1 mm (range 1-5.9) in group II, (p<0.006). CONCLUSIONS: Short-term
      follow-up demonstrated excellent results of ASD closure in both groups. In one
      month follow-up the decrease of right cavities dimensions was significantly
      higher in the patients without tricuspid abnormalities. The pulmonary artery
      systolic pressure before ASD closure was significantly higher in the patients
      with tricuspid abnormality.

PMID- 15724656
TI  - [Ebstein syndrome--various forms, clinical view and treatment results in
      children].
AB  - Ebstein's anomaly is an uncommon lesion of the tricuspid valve characterized by
      downward displacement of the tricuspid valve. The aim of the study was an
      analysis of the form, clinical outcome and treatment results in patients (pts)
      diagnosed with Ebstein anomaly. METHODS: 28 pts were analysed. Material has been
      divided into 3 groups, depending on clinical symptoms. The group A was formed
      with mild shape of the defect, group B all pts presenting significant clinical
      symptoms requiring treatment, and group C made of pts having severe symptoms
      requiring intensive treatment including surgical intervention. RESULTS: Anomaly
      had been detected in 13 boys and in 15 girls. Group A consisted of 6 children,
      including one boy diagnosed with defect prenatally. Described patient currently
      is followed-up in pulmonology outpatient clinic due to asthma. Other children are
      doing well and require no treatment. Group B was represented by 8 children
      requiring treatment of: sepsis, arrhythmia due to WPW syndrome and in one case
      ASD 2. Group C consisted of 14 patients. In 7 pts Ebstein anomaly was part of a
      complex congenital heart defect. In 5 cases dominating symptoms were severe heart
      failure with cyanosis and arrhythmia and in two cases sepsis. 10 pts had been
      treated surgically (7 pts had Blalock-Taussig shunt, 1 pt artificial valve
      replacement, 1 pt Fontan op. and 1 pt ASD 2 suture) where 8 died. The causes of
      death were: right ventricle failure and arrhythmia in 4, sepsis in 2, and
      pulmonary artery hypoplasia and metabolic acidosis also in 2 cases. CONCLUSIONS:
      Ebstein anomaly includes wide spectrum of anatomical and clinical findings. The
      most severe forms require surgical intervention, however it can be a high risk
      procedure.

PMID- 15724657
TI  - [Infections as a preoperative problem in patients with tetralogy of Fallot (TOF)
      associated with complete atrioventricular canal septal defect (AVC)].
AB  - Tetralogy of Fallot (TOF) coexisting with atrioventricular canal septal defect
      (AVC) is a rare combination of anomalies. Additionally, in cases with concomitant
      Down syndrome, recurrent infections can be a serious problem in patients (pts.)
      waiting for cardiosurgery treatment. The purpose of the study was an analysis of
      types of infections and other factors complicating the preoperative period in
      those patients. MATERIAL AND METHODS: The study group consisted of 17 pts. with
      TOF and AVC aged from 1 day to 9 years (mean 9.4 month). In this group there were
      11 pts. with Down syndrome. All of them were subjected to physical examinations,
      blood analysis, ECG, chest X-ray and echocardiographic study. Additionally, in 8
      pts. we performed catheterization. The signs of different types of infection were
      analyzed and results were compared in two groups: with and without Down syndrome.
      RESULTS: The differences were observed in the frequency of recurrent or chronic
      infections (21 v/s 4), time of hospitalization before surgery (17 v/s 9 days),
      necessity (11 v/s 3) and duration of antibiotic therapy (19 v/s 7 days) in the
      two studied groups. Elevated body temperature of unknown etiology was noted in 8
      cases with Down syndrome, compared to 1 patient without trisomy 21. Also, the
      children with Down syndrome had to wait 11 days longer (19 v/s 8) for discharge
      after operation. CONCLUSIONS: Infections in children with TOF, AVC and Down
      syndrome significantly complicate the natural course of this anomaly. Prolonged
      preoperation time is characteristic of Down syndrome pts. compared to patients
      without chromosomal abnormalities.

PMID- 15724658
TI  - [Long-term results of valvular condition and clinical state in patients operated
      with the Senning method].
AB  - 8 patients suffering transposition of the great arteries (d-TGA) aged from 8-17
      years (mean 12.6 years) after Senning procedure performed were analyzed. Right
      atrium and right ventricle enlargement was detected in all patients. Small jet
      tricuspid valve regurgitation was confirmed in 5 patients, significant tricuspid
      valve insufficiency in 3 patients. 4 patients had presented with tricuspid valve,
      aorta valve and mitral valve insufficiency. In one patient insignificant
      pulmonary artery stenosis had been diagnosed. Chronic cardiac failure (NYHA
      III/IV) has been diagnosed in 2 patients, other patients from the analyzed group
      are in good clinical condition. All patients but 2 were diagnosed with arrhythmia
      using 24-hour Holter ECG. In 2 patients sinus node dysfunction was noted. Also
      supraventricular extrasystole, ventricular extrasystole, supraventricular
      tachycardia, ventricular salve, paroxysmal atrial fibrillation were described. No
      drug therapy in 4 patients is needed, one is treated with ACE-inhibitors, one
      with diuretic drugs. 2 patients suffering cardiac failure had been treated with 4
      drugs, also temporary with intravenous dopamine. One death had been noted, caused
      by serious arrhythmia. One patient had been qualified for heart transplantation,
      there is no further data regarding this case. Senning procedure can be considered
      high risk for various problems, so patients who underwent this type of correction
      should be carefully observed.

PMID- 15724659
TI  - [Echocardiographic prediction of outcome in patients with congestive heart
      failure and mitral regurgitation].
AB  - BACKGROUND: Congestive heart failure is associated with the increase risk of
      death or cardiac transplantation. The ability of current techniques to predict
      outcome in heart failure is rather limited. Identification of the patients at
      risk of cardiac death or requiring heart transplantation is clinically important.
      The changing rate of left ventricular pressure during the cardiac cycle is an
      important parameter in the assessment of myocardial systolic function. Non
      invasive echocardiographic method--dP/dt has been proposed to determine the
      isovolumic phase of cardiac function. The aim of this study was to evaluate the
      ability of Doppler-derived dP/dt to predict survival in patients with congestive
      heart failure. MATERIAL AND METHODS: Thirty one patients (22M, 9W), mean age 55
      +/- 11.2 years, with CHF (LVEF < 45%, NYHA II-IV class) and chronic mitral
      regurgitation were analyzed. The echocardiography, cardiopulmonary exercise test
      and clinical follow-up were performed in all of them. The ejection fraction was
      calculated using the Simpson's method from apical 4-chamber view. The dP/dt index
      was derived from the continuous-wave Doppler spectrum. The mean follow-up period
      was 28.5 +/- 12 months. According to the clinical status the patients were
      divided into two groups: group I--21 event-free patients and group II--10
      patients who experienced primary events (5 died and 5 underwent heart
      transplantation). RESULTS: In the group of primary events patients there was
      noted a significant decrease of the dP/dt index in comparison to the event-free
      patients: 463 mmHg/s vs 839 mmHg/s (p=0.0001). The correlation between dP/dt and
      ejection fraction, left ventricular end-diastolic diameter as well as between the
      parameters of cardiopulmonary exercise test VO2peak, VO2AT, VE/VCO2peak was
      found. CONCLUSIONS: Doppler echocardiographic index of dP/dt can predict the
      outcome in patients with congestive heart failure. Dp/dt can be useful as a
      prognostic factor in patients with CHF. A significant correlation was observed
      between dP/dt and VO2peak as well as VE/VCO2peak which are independent prognostic
      predictors.

PMID- 15724660
TI  - [Relationship between Doppler indices of diastolic function and exercise capacity
      in patients with congestive heart failure].
AB  - Exercise intolerance is a major symptom in patients (pts) with congestive heart
      failure (CHF). A lack of correlation between the left ventricular systolic
      dysfunction and exercise capacity was found. Recently, it has been proposed that
      diastolic dysfunction may contribute to significant impairment of exercise
      tolerance in pts with CHF. The aim of the study was to compare the relationship
      between Doppler indices of diastolic function and exercise capacity in patients
      with CHF. MATERIAL AND METHODS: The study included 29 pts (20 M, 9 F) 14 with
      idiopathic and 15 with ischaemic cardiomyopathy. The mean left ventricular
      ejection fraction (LVEF) was 31 +/- 8%, VO2peak was 16.4 +/- 4.6 ml/kg/min. The
      mean age was 55.4 +/- 12.1, ranged from 30 to 73 years. All pts underwent
      complete echocardiography study. Diastolic performance was estimated using
      conventional Doppler mitral inflow (E, A) velocities, E/A ratio, deceleration
      time of E velocity (E-DT), isovolumetric relaxation time (IVRT) and color Doppler
      M-mode flow propagation velocity (Vp). Resting spirometry and cardiopulmonary
      exercise test (CPX) were performed in all pts. Exercise capacity was measured as
      oxygen consumption at peak exercise (VO2peak). The association between
      echocardiography parameters and VO2peak was evaluated by Spearman's correlation
      coefficients (r). RESULTS: We found that VO2peak correlated significantly with
      the LV filling pattern estimated by the transmitral Doppler E/A ratio (r=-0.4,
      p=0.03), A-wave velocity (r=0.4, p=0.03) and velocity flow propagation (r=0.4,
      p=0.05). There was no correlation between VO2peak and following mitral inflow
      parameters: (E-wave, DT, IVRT). There was no correlation between VO2peak and
      LVEF. CONCLUSIONS: 1. Doppler indices of diastolic function are important
      determinants of exercise capacity in CHF pts. 2. Assessment of transmitral flow
      velocities holds a substantial diagnostic potential, which may be utilized in
      everyday clinical practice as a alternative in routine monitoring of systolic
      heart failure.

PMID- 15724661
TI  - [Prognostic value of the parameters of left ventricular systolic function in
      patients with heart failure].
AB  - There are several parameters of left ventricular (LV) systolic function
      assessment. The calculation of the ejection fraction (EF) strongly relates to the
      preload and afterload conditions. Wall motion score index (WMSI) seems to be to
      impractical as the semi-quantitative method. Measurement of the LV pressure rise
      by Doppler evaluation of mitral regurgitation is a reproducible and an accurate
      method for dP/dt evaluation. As a method for LV systolic function estimation it
      does not depend on loading conditions. We have compared the prognostic value of
      these three methods in patients with a broad spectrum of systolic dysfunction.
      The study group consisted of 75 patients evaluated by all these methods in years
      1995-1999 in our echocardiographic laboratory (73%--men, mean 54 +/- 12 years).
      In 13 patients the coronary artery disease was diagnosed but LV function was
      apparently normal, in 35--regional dysfunction after myocardial infarction was
      described, and in 27--global dysfunction due to idiopathic dilated
      cardiomyopathy. The EF ranged from 11% to 70% (mean 34 +/- 14%), WMSI--from 1 to
      3.6 points (mean 2.2 +/- 0.7), and dP/dt from 235 to 4000 mmHg/s (mean 1108 +/-
      698 mmHg/s). The closest relationship was noted between EF and dP/dt (R2=0.50).
      During 38 +/- 19 months of follow-up, 40 patients died (53%). In the multivariate
      logistic analysis the only significant parameter related to prognosis was EF
      (p=0.001). WMSI (p=0.12) and dP/dt (p=0.16) were not statistically significant
      correlated to death. CONCLUSION: The left ventricular ejection fraction still
      remains the most important parameter for the evaluation of prognosis in patients
      with depressed systolic function. Left ventricular pressure rise describes the
      systolic function but does not have impact on the prognostic evaluation.

PMID- 15724662
TI  - [Clinical use of cardiovascular magnetic resonance in viability assessment in
      patients after myocardial infarction--new method].
AB  - After myocardial infarction the assessment of myocardium viability is essential
      for further treatment and prognosis. Many adaptation phenomena occur in the
      ischaemic myocardium. When the compensation mechanisms are exhausted necrosis and
      apoptosis take place. Magnetic resonance is a method which makes possible an
      accurate assessment of myocardium viability and the visualization of the
      irreversible impairment including the scar. This paper defines and systematizes
      the physiopathological phenomena that occur in the ischaemic myocardium. It
      presents the magnetic resonance tomography method as recommended in the
      assessment of the myocardial viability. It compares CMR with other at present
      frequently used methods of myocardium viability assessment. We present particular
      procedures of viability assessment in CMR with special attention drawn to the
      phenomenon of myocardial late enhancement basing on our own three-year experience
      in using magnetic resonance in cardiologic diagnostics.

PMID- 15724663
TI  - [Assessment of ejection fraction by cardiovascular magnetic resonance in
      comparison with 99mTc gated SPECT].
AB  - BACKGROUND: Impaired left ventricular (LV) function with decreased ejection
      fraction (EF) is a frequent finding in patients with ischaemic heart disease. As
      a non-invasive method, cardiovascular magnetic resonance (CMR) has become an
      important diagnostic method in cardiology within the past decade, especially for
      assessing myocardial function. AIM: The purpose of this study is to compare EF
      estimated with 99mTc gated SPECT (GSPECT) and with CMR. METHODS: The study was
      performed in a group of 35 patients (11 F, 24 M; mean age 57 SD 10) after
      myocardial infarction. EF in CMR procedure was calculated using cine gradient
      echo sequences. GSPECT measured EF was estimated by Tc 99. RESULTS: The mean
      value of EF measured with scintigraphy was 50.5 +/- 17%, and measured with CMR
      48.3 +/- 15%. The difference in mean values of EF was not statistically
      significant. CONCLUSIONS: 1. EF in CMR was highly concordant with GSPECT. 2. The
      mean value of EF measured with CMR in 75% of study patients was smaller than in
      the scintigraphy group, but the difference was not statistically significant. 3.
      CMR is a simple, precise and reproducible diagnostic method for monitoring left
      ventricle systolic function, and which is an additional non-invasive imaging
      technique in cardiac diagnosis.

PMID- 15724664
TI  - [Morphology and location of atherosclerotic lesions in coronary vessels depending
      on gender and age].
AB  - Coronary artery disease is a major social problem. However, its epidemiology,
      pathophysiology, clinical course, diagnostic efficiency and therapeutic potential
      differ significantly with regard to gender and age. There are few comparative
      data available on morphological differences and immediate results of direct
      percutaneous interventions, aorto-coronary bypass grafting, complication rate,
      risk factors for developing complications after invasive procedures in CAD
      patients of both sexes and in various age groups. The aim of the study was to
      identify differences in the location and morphology of coronary plaque and left
      ventricular function in CAD patients with regard to gender and age. The study
      included consecutive patients with coronary artery disease diagnosed and treated
      in the Department of Hemodynamics and Angiocardiography Jagiellonian University
      Medical College from June 1997 to June 1998. Coronary angiography group,
      consisting of 1374 patients, 1004 men (73.1%) and 370 women (26.9%), of whom 1146
      (83.4%), 890 men (77.7%) and 256 women (22.3%), were included in the final
      morphological and clinical analysis and in whom coronary angiography confirmed
      the presence of coronary plaque. The subgroups were further subdivided into two
      age groups: below and over 50 years of age. Clinical, angiographic and
      hemodynamic data were analysed retrospectively. Analysis revealed that among
      patients after invasive diagnosis because of suspected coronary artery disease
      atherosclerotic lesions in epicardial coronary vessels were significantly more
      frequently confirmed in men. In patients of both sexes the proportion of patients
      with angiographically confirmed lesions rises with age. In patients with
      angiographically documented coronary artery diseases the location and morphology
      of stenosis in epicardial coronary vessels differs between sexes in the
      corresponding age groups. Left ventricular function is better preserved in women.

PMID- 15724665
TI  - [Comparison of myocardial perfusion assessed by Tc99m MIBI single photon emission
      computer tomography (SPECT) with the Coronary Calcium Score (CS) assessed by
      multi-slice computer tomography (MSCT)].
AB  - BACKGROUND: There is growing evidence regarding evaluation of Coronary Artery
      Calcium Score (CS) using the multi-slice computer tomography (MSCT), but as a new
      method it still need for verification in comparison with other, non-invasive
      modalities, with established rationale. One of these is SPECT, which value in
      evaluation of patients with coronary artery disease is well known. We tried to
      compare these two studies and their usefulness in diagnosis of patients with
      confirmed coronary artery disease. MATERIAL AND METHODS: 72 patients (53 males
      and 19 females, mean age 59.9 +/- 8.66), all after coronary angiography, with
      coronary artery disease (CCS II or III) were included into our study. SPECT and
      exercise treadmill results were compared with the coronary artery calcium score
      (CS) as assessed by MSCT. Both studies were performed with maximal 7-days
      intervals at most between the studies. Image reconstruction was performed using
      the Autoperfusion protocol, with the VISUAL Score analysis (5-point scale) of
      extent of perfusion defect. MSCT was evaluated using the Calcium Score protocol.
      For the statistical analysis we used Student's T-test and Pearson correlation
      analysis. RESULTS: The correlation between total CS and the score of the
      reversible and non-reversible perfusion defects in Tc 99mMIBI SPECT was not
      found. Following the analysis for the 3 main coronary arteries separately, and
      number of perfusion defects, a correlation was observed for LAD and RCA perfusion
      regions. CONCLUSIONS: 1. Statistically significant correlation between CS by MSCT
      and SPECT perfusion deficiencies in the left descending artery (LAD) and right
      coronary artery (RCA) perfusion regions were found. 2. The correlation between
      high CS (>400) and the presence of hemodynamically significant changes in
      coronary angiography was found. 3. We conclude that CS by MSCT may be a screening
      tool of some value for risk stratification.

PMID- 15724666
TI  - [The use of tissue Doppler imaging for the diagnosis of restenosis after
      percutaneous coronary revascularisation].
AB  - OBJECTIVE AND AIM OF THE STUDY: Diagnosis of restenosis after percutaneous
      transluminal coronary angioplasty (PTCA) is difficult due to low sensitivity and
      specificity of widely used methods. The aim of the study was to evaluate the
      usefulness of tissue Doppler Imaging (TDI) in the diagnosis of restenosis in
      comparison with the results of clinical examination, electrocardiographic
      exercise test (ETT) and wall motion score index (WMSI) analysis. MATERIAL AND
      METHODS: 22 patients (18 males, 4 females) aged 46-69 with coronary artery
      disease who underwent PTCA, with restenosis of widen artery found during one-year
      follow-up. The angioplasty of anterior descending artery was made in 16 patients,
      circumflex artery was widened in 2 patients, right coronary artery in 4 patients.
      Clinical and echocardiographic examinations, ETT and TDI were made in all the
      patients before PTCA, one month after PTCA and during restenosis before control
      coronary angiography. In TDI examination maximal systolic and maximal early
      diastolic velocities of myocardium were determined in 18 left ventricle segments.
      RESULTS: After the procedure significant decrease of clinical symptoms and ST
      depression during ETT were found. Restenosis resulted in recurrence of clinical
      symptoms and ETT parameter worsening. No significant changes in the mean values
      of left ventricle ejection fraction was observed after PTCA or during restenosis.
      Mitral inflow E/A ratio was decreased before PTCA, after PTCA and during
      restenosis. In 12 (55%) patients despite significant coronary artery stenosis,
      WMSI was normal (1.0) both before PTCA, after PTCA and during restenosis. In 10
      (45%) patients with anterior descending artery stenosis regional contractility
      disturbances were found before PTCA. After revascularisation WMSI decreased in
      only 4 patients. During TDI examination in patients with contractility
      disturbances before PTCA, revascularisation resulted in significant systolic
      myocardial velocity increase, and restenosis was manifested by renewed systolic
      myocardial velocity decrease. Early diastolic myocardial velocities in ischaemic
      segments were significantly decreased before PTCA in all the patients, and no
      increase were found despite effective PTCA. CONCLUSIONS: Significant coronary
      artery stenosis leads to left ventricle diastolic function disturbances, however
      may not result in systolic dysfunction. After PTCA procedure significant systolic
      left ventricle function improvement, expressed by increase of systolic myocardial
      velocity in ischaemic segments, no changes of diastolic left ventricle function
      is seen. Restenosis in patients after PTCA is manifested by renewed decrease of
      systolic myocardial velocity in ischaemic segments.

PMID- 15724667
TI  - [Left ventricular systolic function in patients with refractory angina pectoris
      treated with percutaneous myocardial laser revascularisation, results of long
      term follow-up].
AB  - INTRODUCTION: Percutaneous myocardial laser revascularisation (PMLR) has been
      developed for treatment of patients with refractory angina pectoris. This study
      was designed to evaluate long-term impact of PMLR on left ventricular systolic
      function. MATERIAL AND METHODS: Ten patients with refractory angina pectoris who
      underwent PMLR were studied with dobutamine stress echocardiography before
      procedure, at early follow-up after 1-3 months and at long-term follow-up after 2
      3 years post procedure. Wall motion score index (WMSI) and ejection fraction (EF)
      were calculated at rest as well during infusion of dobutamine with low and high
      rate. RESULTS: Mean WMSI at rest decreased significantly from 1.71 +/- 0.24
      before PMLR to 1.55 +/- 0.21 at early follow-up (p=0.0189) and 1.48 +/- 0.26
      (p=0.009) at long-term follow-up. Mean WMSI during low-rate dobutamine infusion
      decreased significantly from 1.39 +/- 0.29 to 1.25 +/- 0.25 (p=0.0276) at early
      follow-up, but was not significantly different in long-term. Mean WMSI during
      high-rate dobutamine infusion decreased significantly from 1.83 +/- 0.21 before
      PMLR to 1.56 +/- 0.2 at early follow-up and 1.57 +/- 0.29 (p<0.03) at long-term
      evaluation. Mean EF at rest increased significantly from 48 +/- 8.6% before PMLR
      to 56.9 +/- 7.9% (p=0.0189) at early follow-up. At long-term follow-up mean EF at
      rest was 52.7 +/- 8.3% and was not significantly different from baseline. Mean EF
      during low-rate dobutamine infusion was not significantly different from baseline
      both at early and long-term follow-up. Mean EF during high-rate dobutamine
      infusion increased significantly from 44.5 +/- 8.6% before PMLR to 58.1 +/- 7.0%
      (p=0.0093) at early follow-up while in long-term it was 51.3 +/- 9.8%, which was
      not significantly different from baseline. These changes were accompanied by
      significant decrease of mean CCS score from 3.52 +/- 0.51 before procedure to
      2.54 +/- 0.78 (p<0.0001) after 1 month and 2.78 +/- 0.65 after 24 months.
      CONCLUSIONS: In patients with refractory angina pectoris treated with PMLR
      significant early improvement of systolic left-ventricular function is observed
      with trend toward improvement in long-term. It is accompanied with significant
      long-term angina relief.

PMID- 15724668
TI  - [Right ventricular infarction: novel modalities of treatment].
AB  - Acute right ventricular infarction (RVI) is usually caused by proximal occlusion
      of the right coronary artery. RVI is frequent, as it occurs in as many as one out
      of every two left ventricular interior and/or posterior wall infarctions. The
      involvement of the right ventricle in acute myocardial infarction has been shown
      to be associated with an increased risk of life-threatening arrhythmias and
      sudden cardiac death. Clinical course of RVI can vary from being completely
      silent to cardiogenic shock (seen in 10-15% patients with inferior wall
      infarction). RVI diagnosis is based on clinical signs (hypotension and increased
      jugular venous pressure while pulmonary fields are clear), ECG (ST elevation by >
      or = 1 mm in V4R), echocardiography (right ventricular wall regional motion
      abnormalities and/or right ventricle distension, paradoxical motion of the
      interventricular septum, tissue Doppler), technetium pyrophosphate scanning with
      ventriculography, and invasive patient monitoring. In addition to its important
      diagnostic part, the invasive patient monitoring plays a key role in risk
      stratification and can dynamically guide the treatment (such as fluid loading).
      In most cases, successful reperfusion in the infarct-related artery territory can
      be achieved by interventional management (i.e. angioplasty) or--if the latter is
      not available--by thrombolytic therapy. Patients with arterial hypotension
      require volume expansion which is best guided by the central venous pressure
      (CVP; a measure of the right atrial pressure, RAP) and the pulmonary capillary
      wedge pressure (PCWP). If the hemodynamics does not improve despite optimal fluid
      loading, pharmacological (catecholamine infusion) or mechanical (intra-aortic
      balloon pump) circulatory assistance needs to be implemented. Patients with
      significant sinus bradycardia or 3rd degree AV block may require temporary
      cardiac pacing. In addition, inhalatory nitric oxide (iNO) has been shown to
      reduce right ventricular afterload in a selective manner and its potential
      clinical role is currently being evaluated. Within several months after RVI, the
      right ventricular performance improves in most patients, including those without
      successful reperfusion of IRA. Such patients, however, have an increased risk of
      complications (including sudden death) while the recovery of right ventricular
      function is slow.

PMID- 15724669
TI  - [Atrial fibrillation in a long-term follow-up after mitral valve replacement].
AB  - The aim of the study was to analyse cardiac rhythm after mitral valve replacement
      and to define pre-operative predictive factors for persistence of atrial
      fibrillation. MATERIAL AND METHODS: The study group consisted of 76 consecutive
      pts (54 F, 22 M), mean age 54.8 +/- 8.2 (38-71) years in whom mitral valve
      replacement was performed due to mitral stenosis (15 pts), regurgitation (18 pts)
      or mixed lesion (43 pts). The prevalence of AF after the procedure was analysed
      with relation to age, gender and the following preoperative echocardiographic
      parameters: left atrial size, mitral valve area, mitral regurgitation, tricuspid
      regurgitation and left ventricular ejection fraction. RESULTS: Chronic AF was
      present in 51 pts (67.1%) before the procedure and in 34 pts (44.7%) after 17.3
      +/- 11.9 months (6-46) follow-up, p<0.005. Patients with AF after operation had
      larger left atrium size (58.6 +/- 10.9 vs 51.3 +/- 10.1 mm, p<0.005) and lower
      ejection fraction (53.8 +/- 7.9 vs. 59.9 +/-8.4%, p<0.01) as compared with pts in
      sinus rhythm. Among 51 pts with preoperative chronic AF, 21 pts recovered to
      sinus rhythm (subgroup I) and 30 pts remained in AF (subgroup II) after
      operation. The only significant differences between subgroup I and II were:
      higher prevalence of mitral regurgitation (85.7 vs 60%, p<0.05), larger mitral
      valve area (1.4 +/- 0.3 vs 1.1 +/- 0.6 cm2, p<0.025) and higher ejection fraction
      (58.9 +/- 7.3 vs. 53.4 +/- 8.4%, p<0.025) in subgroup I. CONCLUSIONS: 1. The
      prevalence of AF diminishes significantly after mitral valve replacement. 2.
      Patients with pure mitral stenosis are at higher risk of remaining in AF after
      operation. 3. Preoperative left atrial dimension and LV ejection fraction are the
      most important predictive parameters for persistence of AF.

PMID- 15724670
TI  - [Passive-fixation ventricular lead of DDD pacing system implantation through left
      superior vena cava].
AB  - Passive-fixation of ventricular lead was implanted through left superior vena
      cava (LSVC) and DDD pacing system replaced AAI in a young patient with II degree
      A-V block. Good mechanical stability and proper bioelectrical parameters obtained
      in short-lasting, uncomplicated procedure does not stay in line with world-wide
      approach. It is preferential for active fixation of leads in the right ventricle
      through the LSVC.

PMID- 15724671
TI  - [Patients history following artificial aortic valve and pacemaker implantation].
AB  - The follow-up of 22 patients (out of 31 patients after artificial aortic valve
      and pacemaker implantation between 1982 and 2001) have been evaluated. There were
      15 men aged 30-76 (x=55) and 7 women aged 43-69 (x=59). Aortic valve replacement
      (AVR) was subsequently followed by pacemaker implantation (PI) after
      approximately 16 days. Indication for permanent stimulation were: atrio
      ventricular complete block in 18 patients and atrial fibrillation with slow
      ventricular response in the remaining 4. There were implanted 15 devices of VVI
      type and 7 of VDD type. The duration of follow up was 9-196 (x=56) months. All
      these patients remained in good general state (II degree--19 patients or II/III
      degree--3 patients acc. to NYHA classification). In 21 out of 22 patients,
      atrioventricular conduction disturbances and bradyarrhythmia remained for the
      entire follow-up duration with permanent stimulation (VVI or VAT). In one patient
      the postoperative complete atrio-ventricular block disappeared during follow up,
      24 months after AVR. CONCLUSIONS: 1. The main indication for PI after AVR was
      complete atrio-ventricular block, persisting 2-3 weeks after surgery, without
      accompanying atrial fibrillation. 2. In long term follow up after AVR and PI (VVI
      or VDD) the dominance of 100% capture ventricular pacing have been recorded in
      almost all cases, which holds the decision of early postoperative PI.

PMID- 15724672
TI  - [Short- and long-term follow-up of left ventricular function after surgical
      treatment of chronic mitral valve regurgitation].
AB  - There are conflicting data concerning late LV remodeling following mitral valve
      surgery due to chronic MR. We performed serial echocardiographic evaluation of 35
      consecutive patients prior and following surgical treatment of mitral valve for
      chronic regurgitation. Studies were performed 1 week before operation (exam I),
      then at 1 week (exam II) and 9-13 months (exam III) (mean 11 months) after
      surgery. LVEDD and LVESD and LA size were recorded from parasternal long-axis
      view, and EF was calculated by Teichholtz formula. Statistical significance of
      achieved values was assessed. The study group consisted of 35 patients (25 males,
      10 females, age 63 +/- 9 yrs). All pts were symptomatic due to the significant
      MR: NYHA II (n = 8), III (n = 25), IV (n = 2). All subjects had excluded coronary
      artery disease by coronary angiogram. 30 patients underwent successful mitral
      valve replacement without preservation of subvalvular apparatus and 5 mitral
      valve repair. Echo-Doppler examination before procedure discovered isolated
      significant MR (4+) with left ventricular dilatation (LVEDD 6.6 +/- 0.3 cm, LVESD
      4.3 cm +/- 0.8), LA enlargement (6.0 +/- 1.1 cm), and pulmonary hypertension
      (systolic PAP 46 +/- 16 mmHg). After operation, marked decrease of LVEDD was
      observed (5.7 +/- 0.7 cm, p<0.0001 vs exam I) with only slight decrease of LVESD
      (4.0 +/- 0.6 cm, p<0.05 vs exam I) resulting in a significant decrease in EF (61
      +/- 15.3% vs 57 +/- 4.8%, p<0.01). Significant reduction of LA size and PAP was
      noticed between exam I and III (6.0 +/- 1.1 cm vs 5.22 +/- 0.94 cm, p<0.0001, 46
      +/- 16 mmHg vs 38 +/- 15 mmHg, p<0.01, respectively). CONCLUSIONS: After
      successful surgical treatment of mild-to-moderate symptomatic chronic MR there is
      a gradual fall of LVEDD implying continued ventricular remodeling over several
      months. However, we observed only a slight decrease of LVEDS with subsequent
      decrease of EF that may support the opinion of the crucial role of mitral valve
      apparatus in overall LV performance. EF fall did not preclude, however, reduction
      of pulmonary hypertension and LA diameter in long-term follow up.

PMID- 15724673
TI  - [How to predict the development of severe mitral regurgitation after percutaneous
      mitral commissurotomy?].
AB  - Severe mitral regurgitation after balloon mitral commissurotomy is a major
      complication with poor prognosis. In a series of 1200 consecutive patients who
      underwent percutaneous mitral valvulotomy 62 (5.2%) developed subsequent severe
      mitral regurgitation (MR). These patients were matched with randomly selected 62
      pts who have had successful procedure. Mitral valve and subvalvular morphology
      was graded in both groups by means of the Wilkins score and new MR
      echocardiographic score. The latter takes into account distribution of thickness
      in anterior and posterior mitral leaflets, degree of commissural and subvalvular
      disease involvement, with each component graded from 1 to 4. No differences were
      noticed regarding the Wilkins score between pts with and without MR. MR
      echocardiographic score was significantly greater in MR group. The Wilkins score
      did not correlate significantly with the MR score. Grades for the anterior
      leaflet, commissures and subvalvular apparatus, were also higher in MR group. No
      significant differences were noted in the score for the posterior leaflet. The MR
      echocardiographic score was superior to widely accepted Wilkins score in
      prediction of development of severe MR.

PMID- 15724674
TI  - [Echocardiographic assessment of left atrial volume and emptying in hypertrophic
      cardiomyopathy].
AB  - Left ventricular diastolic dysfunction plays an important role in the
      pathogenesis of symptoms in patients with hypertrophic cardiomyopathy (HCM).
      Theoretically abnormal LV filling should lead to left atrium (LA) enlargement and
      abnormal emptying. Our study was performed in 27 pts with hypertrophic
      cardiomyopathy (mean ventricular septum thickness 2.4 +/- 0.73 cm, mean posterior
      wall thickness 1.23 +/- 0.42 cm and mean LV wall thickness measured at 10
      segments 1.93 +/- 0.37 cm) and 38 healthy volunteers. Transmitral Doppler flow
      parameters (Emax, Amax, t decE, Emax/Amax) did not differ in both groups. We used
      2D echocardiographic automatic borderline detection method to assess the
      following LA volumes during its emptying: maximal volume (LAVmax), volumes at the
      end of rapid emptying (LAV-RE), before atrial contraction--P wave on ECG (LAV-P)
      and minimal LA volume after atrial contraction (LAVmin). We also calculated total
      LA emptying fraction (%LAEF), absolute volume changes during LA early emptying
      (delta LAV-RE) and atrial contraction (delta LAV-AC) and their ratio (delta LAV
      RE/delta LAV-AC). 11 pts had mitral regurgitation. The mitral regurgitation
      fraction was calculated as the ratio of the area of mitral regurgitation to LA
      area. RESULTS: Significantly larger LAVmax (75.8 +/- 28.0 vs 60.7 +/- 18.1 ml,
      p<0.01), LAV-RE (50.4 +/- 21.4 vs 35.3 +/- 13.8 ml, p<0.005), LAV-P (50.7 +/-
      20.5 vs 38.4 +/- 13.8 ml, p<0.01) and LAVmin (33.0 +/- 15.1 vs 26.3 +/- 11.7 ml,
      p<0.05) were found in HCM compared to C. The total LA emptying fraction %LAEF
      (58.0 +/- 11.4 vs 57.4 +/- 12.1%, NS), DLAV-RE (27.3 +/- 12.6 vs 25.3 +/- 11.0
      ml, NS), and ratio delta LAV-RE/DLAV-AC (1.94 +/- 1.22 vs 2.38 +/- 1.10, NS) were
      similar both groups and active emptying delta LAV-AC (17.6 +/- 9.7 vs 12.1 +/-
      5.3 ml, p<0.005) was significantly larger in HCM. The regurgitation fraction
      observed in HCM was 2.7-31.1%. Statistically significant correlation between LA
      total emptying fraction (%LAEF) and mitral regurgitation fraction (r=-0.47,
      p<0.05) and no relations between LA size and function parameters and LV
      hypertrophy parameters were found in HCM. CONCLUSION: LV hypertrophy in
      hypertrophic cardiomyopathy leads to LA enlargement and changes in its emptying.
      We found larger the following LA volumes: maximal volume, volume after early
      emptying, before atrial contraction and minimal volume and greater LA volume
      change during active emptying. Total LA emptying fraction, volume change during
      early/passive emptying and passive/active emptying volumes ratio were similar in
      both groups. No correlation existed between the degree of LV hypertrophy and LA
      volume and emptying parameters. We observed negative relation between mitral
      regurgitation fraction and LA total emptying fraction, but because of small group
      of pts with mitral regurgitation, further studies are needed.

PMID- 15724675
TI  - [Clinical relevance of tricuspid regurgitation after orthotopic heart
      transplantation].
AB  - Tricuspid regurgitation (TR) is common after heart transplantation (OHT). Some
      possible factors include: disturbed geometry of right atria anastomosis with
      subsequent impairment of the functional integrity of the valvular apparatus,
      asynchronous contraction of the donor and recipient atria compartment and damage
      of the sub-valvular apparatus during endomyocardial biopsy. THE PURPOSE OF THE
      STUDY: To determine the incidence of subclinical and severe TR, to evaluate its
      clinical significance, and to assess the risk factors for TR in the heart
      transplantation population. METHODS: OHT was performed in 436 patients between
      1988 and 2002. 112 pts who died during the first 30 days after the operation were
      excluded from the analysis. TR was assessed using transthoracic color Doppler
      echocardiography. TR was graded from 1 to 4. Occurrence of TR in the
      postoperative period was assessed as early (during the first year after OHT) or
      late. The following clinical variables were assessed: preoperative transpulmonary
      gradient and pulmonary vascular resistance, number and grade of rejection
      episodes, postoperative echocardiographic parameters of right ventricular
      function, number of heart biopsies. Stepwise multivariate logistic regression was
      used to correlate the clinical factors with the occurrence of TR. Clinical status
      of the patients with TR was also evaluated. RESULTS: TR of any grade was observed
      in all the patients after OHT. TR > or = 2 grade was determined in 285 pts
      (87.96%). Early occurrence of TR was observed in 80 pts (28.07%). The development
      of early TR was correlated with preoperative raised transpulmonary gradients,
      raised vascular resistance and early rejection greater or equal to grade 2
      (according to ISHLT). Risk factors for late TR: number of rejection episode
      greater or equal to grade 2 (p<0.005) and the total number of heart biopsies
      (p<0.05). Recipients with moderate and severe TR revealed advanced NYHA status
      compared to those with trivial or mild TR. CONCLUSIONS: 1. Moderate to severe TR
      commonly occurs following heart transplantation. 2. Various factors contribute to
      TR after OHT, the prevalence of which may be lowered by early treatment of
      rejection and reduction of the number of biopsies performed.

PMID- 15724676
TI  - [Vasodilatator testing with nitric oxide (bronchial control treatment system-
      BCTS) in patients with pulmonary hypertension].
AB  - Nitric oxide (NO) is one of the most important mediators produced in the human
      organism. It participates in the regulation of blood vessel lumens, activation of
      leucocytes and platelet; it is a mediator in the nervous system and in
      inflammation reactions. It was proved that in cases of patients with pulmonary
      hypertension, a decreased secretion of nitric oxide and an increased synthesis of
      endothelin-1 is observed. Therefore, in case of patients with pulmonary
      hypertension the exogenous, inhaled nitric oxide (iNO) is applied. It is added to
      the respiratory mixture and it passes through the alveolar-capillary barrier to
      the smooth muscle cells where it activates a guanyle cyclase, similarly to the
      physiologically produced nitric oxide. It was proved that it decreases pulmonary
      vascular resistance (PVR) and pulmonary artery pressure (PAP). Inhaled nitric
      oxide is applied for treatment purposes to patients after cardiosurgical
      operations, mainly heart transplantation and correction of valvular defects with
      accompanying pulmonary hypertension, as well as after implantation of the left
      ventricular assist device in order to relieve the right chamber. In case of
      patients qualified for cardiosurgical operations with the accompanying pulmonary
      hypertension as well as in case of patients with the arterial pulmonary
      hypertension a diagnostical test using iNO is carried out in order to determine
      further course of therapeutical treatment. The application of the new method of
      iNO administration by the BCTS (Bronchial Control Treatment System) method allows
      for a precise administration of accurately determined doses of iNO and its full
      utilisation through addition to the respiratory mixture in the initial phase of
      inspiration. The risk of side effects is also decreased; so far no influence on
      the circulatory system or an increase of the level of methemoglobin was observed.

PMID- 15724677
TI  - [Relations between endothelial nitric oxide synthase and angiotensin-converting
      gene polymorphisms and certain biochemical parameters in patients with cardiac
      syndrome X].
AB  - Cardiological syndrome X (CSX) is defined as effort anginal pain, positive
      exercise tolerance test and absence of angiographically documented stenosis in
      coronary arteries. Some genetic predispositions and metabolic disturbances can
      participate in development of this syndrome. The aim of our study was to
      investigate the associations between some biochemical parameters and polymorphism
      of ACE and eNOS (VNTR and Glu298Asp) genes in patients with CSX. 36 patients with
      CSX and a control group of 30 healthy volunteers were included in the study. The
      genotypes were determined by the polymerase chain reaction. Our study revealed
      that patients with CSX exerted lower fasting NOx levels, tended to have higher
      insulin values measured at 1 h of oral glucose tolerance test and higher levels
      of triglycerides and free fatty acids during oral lipid tolerance test. Patients
      with genotype T/T Glu298Asp of eNOS and 4/4 VNTR of eNOS revealed lower levels of
      NOx compared to patients with genotypes G/G and 5/5, respectively (30.5 +/- 7.2
      vs 13.2 +/- 4.5; 28.6 +/- 8.4 vs 14.2 +/- 7.4; p<0.05). Thus, we conclude that
      disturbances in free fatty acid utilization, estimated by postprandial lipaemic
      test play important roles in the development of endothelial injury in CSX.

PMID- 15724678
TI  - [Patients with mitral insufficiency during myocardial infarct in the material of
      the Cardiology Ward in SP ZOZ Sanok].
AB  - The author shows the lifestyle of 13 patients among 314 treated for myocardial
      infarct in the years 1966-2001 on the Cardiological Ward SP ZOZ in Sanok. On
      physical examination a systolic murmur above the heart was diagnosed at the
      moment of hospital admission and in the echocardiography, mitral valve disease of
      the II and III degree was confirmed. Among 12 patients myocardial infarct with Q
      wave was found, in 1 patient myocardial infarct without Q wave. In this group 6
      patients died during the first hours of myocardial infarct, 7 of them developed
      acute myocardial infarct. Due to the rupture of the papillary muscle, artificial
      mitral valve was implanted in one patient; the remainder was qualified for
      invasive diagnosis. The author points out the diminishing systolic murmur during
      fibrinolytic treatment. The author observed--likewise in literature--the
      occurrence of mitral incompetence during the myocardial infarct in 4.1% of
      patients undergoing medical treatment and 46% mortality rate.

PMID- 15724679
TI  - Beauty is truth, truth beauty.

PMID- 15724680
TI  - Zonular dehiscence two years after phakic refractive lens (PRL) implantation.
AB  - PURPOSE: To report two cases of zonular dehiscence two years after phakic
      refractive lens (PRL) implantation. METHODS: In case 1, a 31-year-old myopic
      patient with refraction of -12.75 diopters (D) in the right eye and -20.50 D in
      the left eye, a 12-mm white-to-white measurement, and anterior chamber depth
      (ACD) of 3.7 mm underwent implantation of a -11.0 D and a -15.5 D PRL-101. Two
      years after surgery, a temporal-superior PRL decentration was observed in the
      left eye. In case 2, a 48-year-old pseudophakic patient with refraction of +8 
      2.5 x 20 degrees underwent implantation of a piggyback PRL-200. Two years after
      surgery, an inferior PRL decentration was observed. RESULTS: The PRL was
      explanted in both cases. A zonular dehiscence was found--temporal-superior in
      case 1 and inferior in case 2. CONCLUSIONS: We have stopped implanting PRLs for
      the present time as the cause of this complication has yet to be determined.

PMID- 15724681
TI  - The theoretical vs. measured laser resection for laser in situ keratomileusis.
AB  - PURPOSE: To measure the excimer laser resection during and after laser in situ
      keratomileusis (LASIK) and to determine the rate of stromal ablation and factors
      predicting its measurement. METHODS: A retrospective, comparative, interventional
      case study of 6010 eyes undergoing LASIK surgery was performed. In vivo
      ultrasonic pachymetry was performed as a measure of the laser resection (1'MLR).
      The theoretical laser resection generated by one of three separate excimer lasers
      (Summit Apex Plus, Alcon LadarVision, VISX) was recorded. The change in central
      comeal thickness measured at enhancement surgery (2'MLR) and the change in the
      residual stromal thickness prior to the laser ablation at the primary and
      enhancement procedure (3'MLR) were recorded as separate measures of the laser
      resection. Paired sample t test and regression analysis was performed to
      determine the relationships and to develop a model predictive of laser resection
      for each laser. RESULTS: For all lasers, 1'MLR produced the highest estimate
      compared to 3'MLR. Laser-induced stromal desiccation, microkeratome effects, and
      change in measured flap thickness were the most likely causes for the
      differences. Laser resection was overestimated in the Alcon theoretical laser
      resection group, but underestimated in the Summit and VISX groups. The difference
      between 2'MLR and 3'MLR was due to epithelial hyperplasia, which measured 8.3,
      17.8, and 10.8 microm in the Alcon, Summit, and VISX enhancement groups,
      respectively. Stromal ablation rates were 11.79, 8.26, and 12.71 microm per
      spherical equivalent diopter laser setting for the Alcon, Summit, and VISX
      lasers, respectively, when measured with 3'MLR. Multiple pre- and perioperative
      factors were associated with laser resection. CONCLUSIONS: To accurately predict
      residual corneal thickness, the expected laser resection for an attempted
      refractive change must be known. As the laser resection can be laser-specific,
      the surgeon needs to establish the mean and range of tissue removal for a given
      attempted correction.

PMID- 15724682
TI  - Simulation of eye-tracker latency, spot size, and ablation pulse depth on the
      correction of higher order wavefront aberrations with scanning spot laser
      systems.
AB  - PURPOSE: The aim of this theoretical work was to investigate the robustness of
      scanning spot laser treatments with different laser spot diameters and peak
      ablation depths in case of incomplete compensation of eye movements due to eye
      tracker latency. METHODS: Scanning spot corrections of 3rd to 5th Zernike order
      wavefront errors were numerically simulated. Measured eye-movement data were used
      to calculate the positioning error of each laser shot assuming eye-tracker
      latencies of 0, 5, 30, and 100 ms, and for the case of no eye tracking. The
      single spot ablation depth ranged from 0.25 to 1.0 microm and the spot diameter
      from 250 to 1000 microm. The quality of the ablation was rated by the
      postoperative surface variance and the Strehl intensity ratio, which was
      calculated after a low-pass filter was applied to simulate epithelial surface
      smoothing. RESULTS: Treatments performed with nearly ideal eye tracking (latency
      approximately 0) provide the best results with a small laser spot (0.25 mm) and a
      small ablation depth (250 microm). However, combinations of a large spot diameter
      (1000 microm) and a small ablation depth per pulse (0.25 microm) yield the better
      results for latencies above a certain threshold to be determined specifically.
      Treatments performed with tracker latencies in the order of 100 ms yield similar
      results as treatments done completely without eye-movement compensation.
      CONCWSIONS: Reduction of spot diameter was shown to make the correction more
      susceptible to eye movement induced error. A smaller spot size is only beneficial
      when eye movement is neutralized with a tracking system with a latency <5 ms.

PMID- 15724683
TI  - Potentially accommodating intraocular lenses--an in vitro and in vivo study using
      three-dimensional high-frequency ultrasound.
AB  - PURPOSE: To investigate the accommodative performance of new intraocular lenses
      (IOL) using the advantages of three-dimensional ultrasound biomicroscopy.
      METHODS: An in vitro simulation device was designed to study IOL performance
      using an artificial capsular bag and a stretching device. The haptic region of
      the Akkommodative 1CU (HumanOptics AG) and CrystaLens AT-45 (Eyeonics Inc) was
      visualized in vitro in three dimensions, using an in-house developed three
      dimensional ultrasound biomicroscope. The in vitro results were used to describe
      the in vivo situation in four patients with accommodative implants. RESULTS: The
      haptic position and angulation in consideration of the accommodation state was
      distinguished and analyzed. In the simulation model, a maximal angulation change
      of 4.5 degrees and 4.3 degrees and a maximal forward shift of 0.33 mm and 0.28 mm
      was observed for the AT-45 and 1CU, respectively. In vivo, a change in haptic
      angulation <100 and a maximal forward shift of 0.50 mm was observed for the 1CU.
      These changes correspond to a theoretical approximate value of 0.50 diopters.
      CONCLUSIONS: The in vitro simulation device examined with three-dimensional
      ultrasound biomicroscopy provided information on the accommodative performance of
      these potentially accommodative IOL designs. Using three-dimensional ultrasound
      biomicroscopy, corresponding changes in haptic angulation during pharmacological
      induced accommodation were observed.

PMID- 15724684
TI  - Corneal higher order wavefront aberrations after hyperopic laser in situ
      keratomileusis.
AB  - PURPOSE: To evaluate the changes in corneal higher order wavefront aberrations
      after hyperopic laser in situ keratomileusis (LASIK). METHODS: In a prospective
      case series, 15 eyes of 12 patients who had hyperopic LASIK were evaluated.
      Corneal topography was obtained before and after hyperopic LASIK with a Nidek EC
      5000 laser using 5.5/8.0 ablation zones. Using anterior corneal height data, the
      changes in corneal higher order wavefront aberrations were calculated. RESULTS:
      The surgery significantly increased both corneal coma-like aberration
      (preoperative/6 months postoperative, 0.054/0.147 [172% increase] for 3-mm pupil
      and 0.381/1.076 [182% increase] for 6-mm pupil) and corneal spherical-like
      aberration (preoperative/6 months postoperative, 0.039/0.067 [72% increase] for 3
      mm pupil and 0.297/0.959 [223% increase] for 6-mm pupil). The surgery
      significantly decreased Zernike coefficient 12 and the polarity of corneal
      spherical aberration changed from preoperative positive value to negative
      postoperatively. For a 3-mm pupil, the achieved changes in spherical equivalent
      refraction significantly correlated with the induced changes in the corneal coma
      like aberration (R = 0.629, P = .010), but not with those in corneal spherical
      like aberration (R = 0.408, P=.133) or Zernike coefficient 12 (R = -0.301, P =
      .282). For a 6-mm pupil, the achieved changes in spherical equivalent refraction
      significantly correlated with the induced changes in the corneal spherical-like
      aberration (R = 0.862, P < .0001) and Zemike coefficient 12 (R = -0.872, P <
      .001) but not with those in corneal coma-like aberration (R = 0.449, P = .094).
      CONCLUSIONS: Hyperopic LASIK significantly increases corneal coma-like and
      spherical-like aberrations and changes corneal spherical aberration from a
      positive to negative value.

PMID- 15724685
TI  - Hyperopic laser in situ keratomileusis with 5.5-, 6.5-, and 7.0-mm optical zones.
AB  - PURPOSE: To evaluate the results of laser in situ keratomileusis (LASIK) for the
      correction of hyperopia and hyperopic astigmatism using a large 7.0-mm optical
      zone and to compare them with treatments using a 5.5- and 6.5-mm optical zone.
      METHODS: One hundred sixty-one eyes of 89 patients with a mean preoperative
      spherical equivalent refraction of +2.44 +/- 1.32 diopters (D) (range: +0.00 to
      +5.62 D, cylinder 5.25 to 0.00 D) were treated for hyperopia and hyperopic
      astigmatism using a 7.0-mm optical zone and were analyzed retrospectively.
      Postoperatively, patients were examined after 1 day, 1 week, 1 month, 3 months,
      and 1 year. Eyes treated previously at the same center by the same surgeons with
      5.5- and 6.5-mm optical zone applications were used as controls. All treatments
      were performed with the Nidek EC 5000 CXII excimer laser system (Nidek, Gamagori,
      Japan). A nasal hinged flap was created using the Nidek MK 2000 microkeratome in
      all cases. RESULTS: The mean postoperative spherical equivalent refraction after
      1 month (n=89) was +0.12 +/- 0.72 D (range: -1.75 to +2.75 D), +0.13 +/- 0.74 D
      (range: -1.88 to +1.62 D) at 3 months (n=70), and +0.20 +/- 0.69 D (range: -1.62
      to +1.12 D) at 1 year (n=33). Regression between 1 month and 1 year was 0.08 D in
      the 7.0-mm optical zone group. Regression was 0.25 D in the 5.5-mm group and 0.02
      D in the 6.5-mm optical zone group between 1 month and 1 year. In both the 5.5-
      and 6.5-mm optical zone groups, 13% of eyes lost one line in visual acuity (2% in
      the 7.0-mm optical zone group). The gain of one or more lines in visual acuity
      was 19% in the 5.5-mm group, 17% in the 6.5-mm group, and 27% in the 7.0-mm
      optical zone group. All data represent primary cases without retreatment.
      CONCLUSIONS: Increasing the optical zone size from 5.5 mm to 6.5 mm and to 7.0 mm
      seems to improve refractive results, stability, and safety of hyperopic and
      hyperopic-astigmatic LASIK treatments. Although some hyperopic and astigmatic
      eyes are endangered by loss of lines in best spectacle-corrected visual acuity,
      more eyes gain one or more lines.

PMID- 15724686
TI  - Assessing the value of laser in situ keratomileusis by patient-reported outcomes
      using quality of life assessment.
AB  - PURPOSE: To assess the value of laser in situ keratomileusis (LASIK) by patient
      reported outcomes using quality of life assessment. METHOD: This study included
      288 consecutive patients treated by LASIK between July and December 2001 at two
      eye clinics. A Myopia-specific Quality of Life Questionnaire was developed in
      this study. The baseline quality of life corresponding to the situation where
      refractive error was corrected by glasses or contact lenses before LASIK
      treatment was evaluated by self-administered questionnaire. The evaluation was
      repeated at 4 days, and 1, 3, and 6 months after LASIK treatment. All question
      items were rated on a scale ranging from 1 (maximal dysfunction) to 5 (minimal
      dysfunction). RESULTS: Factor analysis identified 34 questions in 4 subscales
      visual function, visual symptoms, social role function, and psychological well
      being. The Myopia-specific Quality of Life Questionnaire subscales proved to be
      internally consistent (Cronbach alpha = 0.70-0.95). Criterion validity was
      assessed by evaluating Spearman correlation between the overall or domain
      specific quality of life and traditional measures of patient status. Overall
      Myopia-specific Quality of Life Questionnaire score changed from 3.21
      preoperatively to 3.76, 4.00, 4.07, and 4.11 at 4 days, and 1, 3, and 6 months
      after surgery, respectively. Social role function showed the biggest improvement
      (score change: 1.51, P < .05), followed by psychological well-being (0.90, P <
      .05), visual function (0.72, P < .05), and visual symptoms (0.49, P < .05).
      Regression analysis results showed that the degree of uncorrected visual acuity,
      discomfort associated with myopia preoperatively, and location of eye center were
      significant factors affecting the magnitude of changes in quality of life after
      LASIK. CONCLUSIONS: This study confirms that the value of LASIK went beyond the
      clinical achievement of refractive correction and extended to the improvement of
      quality of life.

PMID- 15724687
TI  - Triptans and the incidence of epithelial defects during laser in situ
      keratomileusis.
AB  - PURPOSE: To investigate whether the incidence of epithelial defects during laser
      in situ keratomileusis (LASIK) was different in patients who were taking
      sumatriptan (Imitrex, Glaxo Smith Kline, Pittsburgh, Pa) for migraine headaches
      than in those who were not. METHODS: A retrospective chart review was performed
      on 54 eyes of 28 patients who had been identified as taking sumatriptan and had
      undergone LASIK at Minnesota Eye Consultants between 1999 and 2001. These
      patients were compared with 54 gender- and age-matched control eyes operated on
      with the same microkeratome at the same location during the same period of time.
      The incidence of epithelial defects during LASIK was compared between the two
      groups. RESULTS: In the sumatriptan group, 11.1% (6 of 54) of eyes developed
      epithelial defects as compared to 9.3% (5 of 54) of eyes in the non-triptan group
      (P=.75, chi square). More recent sumatriptan exposure did not increase the
      incidence of epithelial defect (P=.47). In patients in whom sumatriptan was
      stopped >1 month prior to LASIK, 6.3% (1 of 16 eyes) had epithelial defects; in
      patients in whom sumatriptan was stopped <1 month prior to LASIK, 14.3% (4 of 28
      eyes) developed epithelial defects; and 9.3% (5 of 54 eyes) of patients in whom
      no triptans had ever been used had epithelial defects (P=.70). CONCLUSIONS: There
      is no correlation between the use of sumatriptan for relief of migraine headaches
      and the generation of epithelial defects during LASIK. There appears to be no
      reason to stop triptans before proceeding with LASIK.

PMID- 15724689
TI  - Non-contact holmium:YAG laser thermal keratoplasty for hyperopia: two-year follow
      up.
AB  - PURPOSE: We evaluated the safety and efficacy of the non-contact holmium:YAG
      laser thermal keratoplasty (LTK) for the treatment of mild to moderate hyperopia
      without astigmatism. METHODS: A prospective, non-comparative case series included
      50 eyes of 28 patients (aged > or =40 years) who had stable refraction and an
      astigmatic component < +0.50 diopters (D). We applied the non-contact pulsed
      holmium:YAG laser to treat the hyperopic spherical component using the Hyperion
      LTK System. All patients had minimum 12-month follow-up and 64% (18 patients) had
      24-month follow-up. RESULTS: The mean age of patients was 48.4 +/- 8.23 years
      (range: 40 to 62 years). The preoperative hyperopic mean spherical equivalent
      refraction was +2.32 +/- 0.975 D (range: +1.00 to +4.75 D). Postoperatively, the
      subjective manifest refraction decreased from the preoperative mean value of
      +2.32 D to a mean -0.09 D at 1 month after surgery and regressed to +0.315 D at
      the last follow-up examination, resulting in a mean correction of +2.005 +/- 0.81
      D at 24 months after surgery. Preoperatively, mean uncorrected visual acuity in
      LogMAR units was 0.798 +/- 0.353 and at 12 months after surgery, it was a mean
      0.108 +/- 0.136. Keratometric power increased from 42.595 +/- 1.949 D before
      surgery to 44.605 +/- 1.626 D at 24 months after surgery. CONCLUSIONS:
      Holmium:YAG LTK was an acceptable alternative for the correction of mild to
      moderate hyperopia in this middle-aged population.

PMID- 15724688
TI  - Ocular integrity after anterior ciliary sclerotomy and scleral ablation by the
      Er:YAG laser.
AB  - PURPOSE: To establish the risk of ocular rupture after proposed surgical reversal
      of presbyopia by anterior ciliary sclerotomy (ACS) or by the Er:YAG laser (HOYA
      Continuum, Tokyo, Japan). METHODS: A total of 45 pig eyes (15 control eyes) were
      examined. Fifteen eyes were placed into one of two study groups and another 15
      eyes were used as controls. One group underwent scleral incisions with the use of
      a diamond knife, and the other group underwent Er:YAG laser scleral incisions. In
      both study groups, 8 radial incisions, 2 parallel cuts each at 4 quadrants, 2 mm
      apart, 4 mm long, and starting 2 mm away from the limbus, were made. A 3-kg steel
      weight was released from a measured height to the pig's eye, and ocular rupture
      energy (joules) was measured. RESULTS: The mean rupture energy was 26.0 J for
      control eyes, 15.7 J for the ACS eyes, and 12.2 J for the Er:YAG laser eyes. The
      ACS and the Er:YAG laser eyes ruptured at significantly lower energies (ACS, P <
      .001; Er:YAG, P < .001) than the control eyes. Comparison of the ACS group and
      the Er:YAG laser group showed no statistically significant difference (P = .052)
      in rupture energy. CONCLUSIONS: Scleral incisions by ACS and the Er:YAG laser
      significantly weakened ocular integrity compared with control eyes. Any patients
      undergoing ACS or Er:YAG laser scleral incision should be informed of the
      attendant potential risk after ocular trauma.

PMID- 15724691
TI  - Comparison of the Colvard pupillometer and the Zywave for measuring scotopic
      pupil diameter.

PMID- 15724690
TI  - US trends in refractive surgery: 2003 ISRS/AAO survey.
AB  - PURPOSE: To determine the latest trends in refractive surgery in the United
      States. METHODS: All U.S. members of the International Society of Refractive
      Surgery of the American Academy of Ophthalmology were mailed the 2003 refractive
      surgery survey dealing with volumes, types, preferences of refractive surgery
      performed, and use of new emerging technology. Questions regarding radial
      keratotomy (RK), astigmatic keratotomy (AK), limbal relaxing incisions (LRI),
      photorefractive keratectomy (PRK), laser in situ keratomileusis (LASIK), laser
      subepithelial keratomileusis (LASEK), intracorneal ring segments (ICRS), laser
      thermokeratoplasty (LTK), conductive keratoplasty (CK), phakic intraocular lenses
      (PIOL), clear lens extractions (CLE), and scleral expansion (SE) procedures were
      examined in the survey. Use of lasers, microkeratomes, pupillometry instruments,
      postoperative medications, wavefront analyzers, topographers, etc were examined.
      RESULTS: In 2003, LASIK continued to dominate for refractive errors between -8.00
      to +3 diopters. Surgeons are waiting on the PIOL for high myopes and are
      performing CLE for high hyperopes. Photorefractive keratectomy, LASIK, LASEK,
      CLE, PIOL, and CK appeared to have bright futures; whereas, RK, ICR, LTK and SE
      were on the decline. Bilateral LASIK at the same surgical session is offered by
      98% of surgeons. VISX lasers are used 2:1 over all other lasers in the United
      States. Zeiss-Humphrey still dominates topographers at 37%. The Bausch & Lomb
      Hansatome (48%) leads microkeratomes. Surgeons are charging, on average, 300-500
      dollars more per eye for custom ablations and these ablations have already been
      accepted and integrated into refractive practices. Comanaging of refractive
      surgery patients is significantly down from previous years. Fourth-generation
      fluoroquinolones overtook the postoperative antibiotic prescriptions, with
      prednisolone and fluoromethalone dominating as anti-inflammatories. CONCLUSIONS:
      Trends and changes as refractive surgery grows in the mainstream of ophthalmology
      in the United States continue to be elucidated by this professional organization
      survey.

PMID- 15724692
TI  - LASIK flap dislocation by blunt trauma seven weeks after surgery.

PMID- 15724693
TI  - Bacterial keratitis after laser subepithelial keratectomy.

PMID- 15724694
TI  - Incidence of bacterial keratitis after photorefractive keratectomy.

PMID- 15724695
TI  - [New approach in the diagnosis and monitoring of treatment in chronic myelogenous
      leukemia].
AB  - The chronic myelogenous leukemia is a pluripotent hemopoietic stem cell disease
      characterized by the t(9;22) (q34;q11) reciprocal chromosomal translocation
      (Philadelphia chromosome). The translocation result the fusion of the ABL gene
      located at the long arm of chromosome 9 with the BCR gene located at the long arm
      of chromosome 22. The BCR/ABL fusion gene encodes a chimeric protein with
      elevated tyrosine kinase activity, that plays an important role in the
      pathogenesis of the disease. In the diagnosis of chronic myelogenous leukemia and
      in the evaluation of the therapeutic effect, the detection of the
      t(9;22)(q34;q11) translocation and BCR/ABL fusion gene plays an important role.
      The authors in the present paper provides a review on the recently used methods
      of the detection of t(9;22)(q34;q11) chromosomal translocation and BCR/ABL fusion
      gene and their role in the diagnosis, monitoring and evaluation of therapeutic
      effect in chronic myelogenous leukemia.

PMID- 15724696
TI  - [Diagnosis and treatment of haemodynamically significant fetal tachycardia--in 33
      cases].
AB  - INTRODUCTION: Fetal tachycardia may lead to an increased pre- and postnatal
      morbidity and mortality rate particularly if it is complicated by cardial
      decompensation and hydrops fetalis. AIM AND METHODS: In this study 33 fetal
      tachycardia cases diagnosed and treated between 1993 and 2004 in the fetal
      echocardiography unit of the I. Department of Obstetrics and Gynecology of the
      Semmelweis University, Budapest are reviewed. The data of postnatal care of the
      newborns delivered in the author's department from these pregnancies, and the
      follow up data provided by the National Institute of Cardiology are examined as
      well. RESULTS: Mean gestational age at diagnosis of fetal tachycardia was 30
      weeks (21-41 weeks). The tachyarrhythmias were classified into atrial flutter (n
      = 8), supraventricular tachycardia (n = 18), arrhythmia absoluta (n = 5),
      parasystole (n = 1) and brady-tachyarrhythmia (n = 1). Six cases were complicated
      by hydrops fetalis, 13 cases by cardial dysfunction. Transplacental
      antiarrhythmic therapy was applied in 22 cases, in 8 cases the newborns were
      delivered because of advanced gestational age, in 3 cases tachyarrhythmia
      resolved spontaneously or therapy was not indicated. The drug of first choice for
      transplacental therapy was digoxin, which was combined with amiodarone or
      verapamil (n = 10). Transplacental therapy led to cardioversion in 13/22 cases.
      The outcome of the 33 examined pregnancies was live birth in 27 cases, in utero
      death in 3 cases and 3 newborns were delivered elsewhere. The postnatal
      documentation of 24 newborns out of the 27 born in the author's department is
      available. At the time of birth 15/24 newborns were in sinus rhythm--out of whom
      5 developed tachyarrhythmia later during the neonatal period--, 9/24 were
      tachycardic. Out of the 14 cases of tachyarrhythmia detected in the neonatal
      period altogether 3 resolved spontaneously, in 7 cases antiarrhythmic therapy was
      successful, in 4 cases unsuccessful. In 2 of these latter cases electrical
      cardioversion led to sinus rhythm. Neurological disorder was not detected in any
      case. In the early postnatal period 2 in utero severely decompensated newborns
      died. The follow-up data of 10 children is available, the follow-up period ranges
      between 6 weeks and 5 and a half years. All 5 children with history of
      supraventricular tachycardia are in sinus rhythm, 3 of them after suspending
      antiarrhythmic treatment, while the other 2 still on antiarrhythmic medication.
      Four out of 5 children with history of atrial flutter are in sinus rhythm, 2 of
      them left antiarrhythmic therapy, and 2 of them still take antiarrhythmic agents
      after electrical cardioversion. The atrial flutter of a 3 month old child could
      not be controlled yet permanently, despite several drug combinations applied.
      CONCLUSIONS: Survival and late prognosis of tachycardic fetuses treated in utero
      is good. A prospective study of even more cases is required to establish uniform
      therapeutic guidelines and to provide appropriate follow-up data.

PMID- 15724697
TI  - [Warfarin or acenocoumarol is better in the anticoagulant treatment of chronic
      atrial fibrillation?].
AB  - A SPORTIF-III substudy. BACKGROUND: Warfarin has been considered to provide more
      stable anticoagulant effect than acenocoumarol due to its longer half-life.
      OBJECTIVE: The aim of this SPORTIF-III substudy was to compare acenocoumarol (A)
      with warfarin (W) in the same group of 74 patients, with chronic atrial
      fibrillation who started with W and then changed to A. METHODS: We compared
      prospectively a 3 months period on W with a 3 months period on A. RESULTS: The
      mean number of INR measurements per patient was 5.7 +/- 1.2 and 5.4 +/- 1.6 resp
      (NS). The mean percentage of INR-s in the therapeutic range of 2-3 was 49 +/-
      22.6% for W and 56 +/- 26.8% for A (p < 0.05), the percentage of subtherapeutic
      values were not different, the supratherapeutic values however occurred more
      frequently on W (28 +/- 20%) than on A (19 +/- 19%), p < 0,001. There was a good
      correlation between A and W doses (r = 0.65, p < 0.001), the mean W dose was 5.03
      +/- 1.99 mg, the mean A dose was 2.5 +/- 1.3 mg, the W/A dose ratio was computed
      to be 2.18 +/- 0.78. CONCLUSIONS: 1. anticoagulation effect stability was
      superior for A compared to W; 2. W/A dose ratio was 2.18.

PMID- 15724698
TI  - [Antioxidant characteristics of a newly developed vermouth wine].
AB  - INTRODUCTION: The polyphenol compounds can be responsible for the beneficial
      physiological effects of the wine, specially of the red wine. The supposed
      mechanism in health protecting effect due to the polyphenol components in the
      wine can be grouped to several biochemical reactions. One of the most important
      and mostly examined characteristics is their antioxidant and radical scavenging
      effect. AIM OF THE STUDY: Examination of the antioxidant characteristics of a
      newly developed vermouth wine. METHODS: Antioxidant characteristics of a newly
      developed vermouth wine (marked with FB) till now not in the market were studied
      comparing with those of three red and three white wines as well as of one rose
      wine. The total polyphenol content, the hydrogen donor activity, the reduction
      capacity and the complex building activity were determined. RESULTS: Hundred ml
      of the vermouth wine involves 18.8 mg alcohol, as well as 220 mg polyphenol
      compounds, comparing to the mean polyphenol content of white wine with 10.5 mg
      alcohol and 35 mg polyphenol contents. CONCLUSIONS: Usual consumption of one unit
      from the vermouth wine examined in this paper is medically acceptable,
      furthermore the organism can have those polyphenol compounds which play
      substantial role in the protection against oxidative stress.

PMID- 15724699
TI  - [Long-term management after myocardial infarction (Part 2.): Medical
      interventions].

PMID- 15724700
TI  - [The bath of Honourable Prince: Vihnye].

PMID- 15724701
TI  - [Markusovszki or Markusovszky].

PMID- 15724702
TI  - Low-income, employer participation facilitated in final rule.

PMID- 15724703
TI  - Perspectives. Budget cutters vs. entitlement programs: back to the BBA?

PMID- 15724704
TI  - The Enter-net and Salm-gene databases of foodborne bacterial pathogens that cause
      human infections in Europe and beyond: an international collaboration in
      surveillance and the development of intervention strategies.
AB  - The free movement of people and foodstuffs between countries are effective ways
      of distributing disease internationally. There is a requirement for a mechanism
      whereby data and information on potential outbreaks of foodborne pathogens can be
      disseminated rapidly to those who need to know. The Enter-net dedicated
      surveillance network provides this mechanism, complemented by the Salm-gene
      molecular typing network. Data on epidemiological and microbiological features on
      current cases, as well as background levels of infections are immediately
      available within the Enter-net databases. The Salm-gene network with its database
      of harmonized salmonella PFGE patterns from the participating European countries
      provides immediate, and electronically exchangeable, DNA fingerprints of outbreak
      strains. This prompt electronic dissemination of information regarding unusual
      events with international implications ensures that public health interventions
      can be implemented and cases of foodborne disease prevented.

PMID- 15724705
TI  - A one-year intensified study of outbreaks of gastroenteritis in The Netherlands.
AB  - In 2002, in The Netherlands a national study of gastroenteritis outbreaks was
      performed. Epidemiological information was collected by the Public Health
      Services (PHS) and the Food Inspection Services (FIS) using standardized
      questionnaires. Stool samples were collected for diagnostic testing. For
      foodborne outbreaks, food samples were taken. In total, 281 gastroenteritis
      outbreaks were included, mainly from nursing homes and homes for the elderly
      (57%), restaurants (11%), hospitals (9%) and day-care centres (7%). Direct person
      to-person spread was the predominant transmission route in all settings (overall
      78%), except for restaurant outbreaks where food was suspected in almost 90%
      (overall in 21% of outbreaks). The most common pathogen was norovirus (54%),
      followed by Salmonella spp. (4%), rotavirus group A (2%), Campylobacter spp. (1%)
      and only incidentally others. In conclusion, most outbreaks were reported from
      health and residential institutions, with norovirus as the dominant agent.
      Control should aim at reducing person-to-person spread. In foodborne outbreaks
      norovirus was common, due to contamination of food by food handlers. Salmonella,
      as the second foodborne pathogen, was mainly associated with raw shell eggs.
      These results stress the continuous need for food safety education, complementary
      to governmental regulation.

PMID- 15724706
TI  - Outbreak of cyclosporiasis in British Columbia associated with imported Thai
      basil.
AB  - Sporadic outbreaks of cyclosporiasis, a common cause of protracted diarrhoea in
      underdeveloped countries, are often undetected and undiagnosed in industrial
      countries. In May 2001, an outbreak of Cyclospora cayetanensis gastroenteritis
      was identified in British Columbia, Canada, with 17 reported cases. We conducted
      a case-control study involving 12 out of the 17 reported and confirmed case
      patients. Eleven (92%) of the patients had consumed Thai basil, an essential
      ingredient in Vietnamese cuisine, compared to 3 out of 16 (19%) of the control
      patients (P = 0.003). Trace-back investigations implicated Thai basil imported
      via the United States as the vehicle for this outbreak. This is the first
      documented sporadic outbreak of cyclosporiasis linked to Thai basil in Canada,
      and the first outbreak of cyclosporiasis identified in an ethnic immigrant
      population. This outbreak provides the opportunity to increase our understanding
      of this emerging pathogen and improve on our prevention and control for future
      outbreaks.

PMID- 15724707
TI  - A large outbreak of scombroid fish poisoning associated with eating escolar fish
      (Lepidocybium flavobrunneum).
AB  - In August 2003, an outbreak of scombroid fish poisoning occurred at a retreat
      centre in California, USA. In a retrospective cohort study, 42 (75%) of the 56
      dinner attendees who ate escolar fish (Lepidocybium flavobrunneum) met the case
      definition. Individuals who ate at least 2 oz of fish were 1.5 times more likely
      to develop symptoms than those who ate less (relative risk 1.5, 95% confidence
      interval 0.9-2.6), and to develop more symptoms (median 7 vs. 3 symptoms, P =
      0.03). Patients who took medicine had a longer duration of symptoms than those
      who did not (median 4 vs. 1.5 h, P = 0.05), and experienced a greater number of
      symptoms (median 8 vs. 3 symptoms, P = 0.0002). Samples of fish contained
      markedly elevated histamine levels (from 2000 to 3800 ppm). This is one of the
      largest reported outbreaks of scombroid fish poisoning in the United States and
      was associated with a rare vehicle for scombroid fish poisoning, escolar.

PMID- 15724708
TI  - A large-scale gastroenteritis outbreak associated with Norovirus in nursing
      homes.
AB  - An increase in gastroenteritis outbreaks due to Norovirus has been reported
      worldwide. We investigated a large-scale outbreak affecting 246 residents and 33
      staff members in six nursing homes in the Tel-Aviv district, Israel, during 3
      weeks in 2002. Person-to-person spread was noticed in all nursing homes. The
      spread of disease could not be attributed to social interactions. Among the
      elderly residents, the hospitalization rate was 10.2% and the case-fatality rate
      was 2.0%. Bacteriological cultures were negative. Overall, 7 out of 15 stool
      specimens were positive for Norovirus by RT-PCR. All were sequenced and found to
      be 90% identical. The characteristics of this outbreak and the RT-PCR results
      suggest that illness was caused by Norovirus. Due to the high case-fatality rate
      of Norovirus gastroenteritis, there should be a high index of suspicion when
      encountering a gastroenteritis outbreak among the elderly. This will enable
      prompt action to stop the spread of illness.

PMID- 15724710
TI  - The seasonality of human campylobacter infection and Campylobacter isolates from
      fresh, retail chicken in Wales.
AB  - Seasonal peaks in both human campylobacter infections and poultry isolates have
      been observed in several European countries but remain unexplained. We compared
      weekly data on human campylobacter infections with thermophilic Campylobacter
      isolation rates from fresh, retail chicken samples (n = 514) purchased weekly in
      Wales between January and December 2002. Human isolates (n = 2631) peaked between
      weeks 22 and 25 (early June) and chicken isolates (n = 364) between weeks 24 and
      26 (late June). In the absence of a temporal association, we postulate that the
      seasonal rise in humans is not caused by a rise in isolation rates in poultry but
      that both are more likely to be associated with a common, but as yet
      unidentified, environmental source.

PMID- 15724709
TI  - Detection of multiple enteric virus strains within a foodborne outbreak of
      gastroenteritis: an indication of the source of contamination.
AB  - An outbreak of acute gastroenteritis of suspected viral aetiology occurred in
      April 2003 in the British Royal Fleet Auxiliary ship (RFA) Argus deployed in the
      Northern Arabian Gulf. There were 37 cases amongst a crew of 400 personnel. Of 13
      samples examined from cases amongst the crew, six enteric viruses were detected
      by reverse transcriptase polymerase chain reaction (RT-PCR). Five different
      viruses were identified including, three norovirus genotypes, a sapovirus and a
      rotavirus. No multiple infections were detected. A common food source was
      implicated in the outbreak and epidemiological analysis showed a statistically
      significant association with salad as the source of the outbreak, with a relative
      risk of 3.41 (95% confidence interval of 1.7-6.81) of eating salad on a
      particular date prior to the onset of symptoms. Faecal contamination of the salad
      at source was the most probable explanation for the diversity of viruses detected
      and characterized.

PMID- 15724711
TI  - Molecular epidemiology of Salmonella spp. isolates from gulls, fish-meal
      factories, feed factories, animals and humans in Norway based on pulsed-field gel
      electrophoresis.
AB  - The molecular epidemiology of 98 isolates of Salmonella serovar Agona (n = 27),
      S. Montevideo (n = 42) and S. Senftenberg (n = 29) from wild-living gulls, fish
      meal factories, feed factories, humans and domestic animals was investigated
      using pulsed-field gel electrophoresis (PFGE) and computerized numerical
      analysis. Two of the S. Agona profiles were identified both in gulls and in two
      of the factories. In addition, one of these profiles was detected in two infected
      poultry farms. Two of the S. Montevideo profiles were also identified both in
      gulls and in two of the factories, and one of these profiles was observed in a
      human isolate. Four factories shared an identical S. Senftenberg profile. The S.
      Senftenberg profile found in gulls was not identified in any other source
      investigated. The presence of isolates with identical PFGE profiles indicates
      potential epidemiological links between different factories, as well as between
      gulls and factories.

PMID- 15724712
TI  - Characterization of multidrug-resistance phenotypes and genotypes of Escherichia
      coli strains isolated from swine from an abattoir in Osaka, Japan.
AB  - A total of 455 highly tetracycline-resistant Escherichia coli strains were
      isolated from 84 healthy swine from abattoirs and it was found that 56.9, 43.1,
      22.2, 15.4, 2.6 and 1.5% of strains were resistant to chloramphenicol,
      ampicillin, kanamycin, trimethoprim-sulphamethoxazole, ofloxacin and gentamicin
      respectively. Interestingly, E. coli strains isolated from certain finisher hog
      groups exhibited resistance against 2-7 antimicrobials, but strains isolated from
      multiparous sow groups in each herd were resistant to only 2-4 antimicrobial
      agents. When randomly selected 108 tetracycline-resistant isolates were tested
      for the presence of resistance genes, the following genes tet(A) (n = 6), tet(B)
      (n = 95), tet(D) (n = 1) or both tet(A) and tet(B) (n = 6) were found to be
      distributed among them. Furthermore, 52 isolates carried the integrase 1 gene and
      24 strains gave five different PCR amplicon profiles using primers from the
      variable region of integron. Extensive nucleotide sequence analyses of these
      amplicons revealed the presence of dhfrI, dhfrXII, dfr17, aadA, aadA2, aadA5,
      aadA21, aacA4 and catB3 genes which code for different antibacterial resistance
      proteins.

PMID- 15724713
TI  - Under-notification of giardiasis in Auckland, New Zealand: a capture-recapture
      estimation.
AB  - Estimation of the degree of undercount is important for disease surveillance.
      Capture-recapture techniques are now being used to evaluate the completeness of
      disease ascertainment. This study estimated the level of under-notification of
      giardiasis in the Auckland adult population using a capture-recapture method. Two
      independent datasets of giardiasis cases > or = 15 years were generated from the
      1998-1999 Auckland Giardiasis Study (AGS) case database and cases notified to
      Auckland Regional Public Health Services (ARPHS) for the same period of time.
      Cases were matched and under-notification was estimated using a two-sample
      capture-recapture method. During the 12-month period, 199 cases participated in
      the AGS and 413 cases were notified to ARPHS. The capture-recapture calculation
      indicated that only 49% of cases were notified. Under-notification by a factor of
      2 obscures the true burden of giardiasis. Socio-economic conditions and water
      quality may influence disease notification inversely. Capture-recapture
      techniques are useful in evaluating the completeness of surveillance.

PMID- 15724714
TI  - Genetic analysis of antibiotic-resistance determinants in multidrug-resistant
      Shigella strains isolated from Chilean children.
AB  - A total of 162 clinical isolates of Shigella collected from children in a semi
      rural community of Chile were examined for the presence of genetic determinants
      of resistance to ampicillin, chloramphenicol, tetracycline, and trimethoprim.
      Ampicillin resistance was most frequently associated with the presence of
      bla(OXA) in S. flexneri and with bla(TEM) in S. sonnei. The bla(OXA) gene but not
      bla(TEM) was located in class 1 integrons. The dhfrIa gene encoding for
      resistance to trimethoprim was associated to class 2 integrons and detected
      exclusively in S. flexneri, whereas dhfrIIIc was found in all S. sonnei strains
      and in 10% of the S. flexneri isolates. Cat, coding for choramphenicol
      resistance, and bla(OXA) genes were located in the chromosome in all cases,
      whereas tetA gene, coding for tetracycline resistance, and bla(TEM), dhfrIa and
      dhfrIIIc genes were found either in the chromosome or in conjugative plasmids.
      Our results show a heterogenous distribution of antibiotic-resistance
      determinants between S. flexneri and S. sonnei.

PMID- 15724715
TI  - Measles elimination in Italy: projected impact of the National Elimination Plan.
AB  - A mathematical model was used to evaluate the impact of the Italian Measles
      National Elimination Plan (NEP), and possible sources of failure in achieving its
      targets. The model considered two different estimates of force of infection, and
      the possible effect on measles transmission of the current Italian demographic
      situation, characterized by a below-replacement fertility. Results suggest that
      reaching all NEP targets will allow measles elimination to be achieved. In
      addition, the model suggests that achieving elimination by reaching a 95 % first
      dose coverage appears unlikely; and that conducting catch-up activities, reaching
      high vaccination coverage, could interrupt virus circulation, but could not
      prevent the infection re-emerging before 2020. Also, the introduction of the
      second dose of measles vaccine seems necessary for achieving and maintaining
      elimination. Furthermore, current Italian demography appears to be favourable for
      reaching elimination.

PMID- 15724716
TI  - The impact of Australia's measles control programme over the past decade.
AB  - We reviewed measles surveillance data for 1993-2002 to determine the impact of
      Australia's measles control initiatives. The introduction of a second dose of
      measles-mumps-rubella (MMR) vaccine for 10- to 16-year-olds in 1993 was followed
      by marked reductions in measles notifications and hospitalizations, especially in
      the targeted age group. Further rate reductions were achieved following the
      Measles Control Campaign (MCC) in 1998, which involved a catch-up campaign for
      primary-school-aged children and lowering the age for the second dose of MMR
      vaccine to 4 years. Since the MCC, outbreaks have continued to occur, but most
      had a source case who was infected overseas, which suggests that indigenous
      transmission has been interrupted. In addition, a greater proportion of cases
      have been in adults although infants aged < 5 years still had the highest rates.
      In conclusion, Australia is making good progress towards measles elimination.
      However, as in other countries, this progress can be sustained only by
      maintaining high vaccination coverage with the routine childhood vaccination
      schedule.

PMID- 15724717
TI  - Summer outbreak of respiratory disease in an Australian prison due to an
      influenza A/Fujian/411/2002(H3N2)-like virus.
AB  - An outbreak of influenza A occurred in a prison system in New South Wales,
      Australia in January 2003 during the southern hemisphere summer. This report
      documents only the third confirmed outbreak of influenza in a prison environment.
      The outbreak investigation included case ascertainment, state-wide surveillance,
      a case-control study and interventions to limit the outbreak such as infection
      control, quarantine, cohorting of cases, and the use of antiviral medication for
      prophylaxis. A total of 37 clinical cases were identified. Influenza A virus was
      detected in 11 of the 22 respiratory tract specimens collected. The virus was
      typed as an influenza A/Fujian/411/2002 (H3N2)-like virus. This strain
      subsequently became the predominant virus strain during the northern hemisphere
      winter and the following 2003 Australian southern hemisphere winter influenza
      season.

PMID- 15724718
TI  - The importance of imported infections in maintaining hepatitis B in The
      Netherlands.
AB  - In The Netherlands, in May 1999 an enhanced surveillance of hepatitis B was begun
      to collect detailed information of patients with acute hepatitis B virus (HBV)
      infection. The objective was to gain insight in transmission routes and source of
      infection of new HBV cases. Through public health services, patients were
      interviewed on risk factors. It appeared that the majority (59%) acquired the
      infection through sexual contact; 52% of these by homosexual and 48% by
      heterosexual contact. In 60% of the heterosexual cases, the source of infection
      was a partner originating from a hepatitis B-endemic region. Sexual transmission
      is the most common route of transmission of acute hepatitis B in The Netherlands
      and introduction of infections from abroad plays a key role in the current
      epidemiology of HBV. As well as prevention programmes targeted at sexual high
      risk groups, prevention efforts should focus more on the heterosexual
      transmission from HBV carriers.

PMID- 15724719
TI  - Estimating the mortality rate of hepatitis C using multiple data sources.
AB  - The New York State hospital discharge database and the multiple cause-of-death
      file were used to estimate the mortality rate of hepatitis C in New York State
      excluding New York City in 1997. The mortality rate with hepatitis C was severely
      underestimated when each data source was used alone. Applying the capture
      recapture method using the hospital discharge database and the multiple cause-of
      death file appears to be an efficient method to estimate the mortality rate with
      hepatitis C.

PMID- 15724720
TI  - Prevalence of hepatitis C in drug users in Flanders: determinants and geographic
      differences.
AB  - The prevalence of hepatitis C and related risk factors in drug users were
      compared in two geographic regions in Belgium, the city of Antwerp and the mixed
      urban-rural area of Limburg. All 310 participants were surveyed and screened for
      hepatitis B, hepatitis C and HIV. Prevalence rates of anti-HCV, anti-HBc and anti
      HIV were 71, 62 and 4% in Antwerp and 46, 21 and 0% in Limburg respectively.
      Injecting drug use, duration of injecting drug use, work as a commercial sex
      worker, originating from Turkey or Northern Africa, marginalization and anti-HBc
      positivity were identified as independent predictors for hepatitis C infection.
      In this study an important difference in HCV seroprevalence among drug users in a
      methadone maintenance programme across two geographic regions in Belgium was
      demonstrated. This was explained not only by variations in drug-related risk
      behaviour, but also by differences in sexual risk behaviour and socio-economic
      status.

PMID- 15724721
TI  - Prolonged persistence of bovine herpesvirus in small cattle herds: a model-based
      analysis.
AB  - Herpesviruses can remain dormant in once-infected hosts and, upon reactivation,
      cause such hosts to become infectious. This phenomenon of latency and
      reactivation may enable herpesviruses to persist for a long time in small host
      populations. To quantify the effect of reactivation on persistence, the time to
      extinction of bovine herpesvirus type 1 (BHV-1) in small cattle populations was
      calculated. For realistic parameter values the mean time to extinction is already
      more than 100 years in a population of 10 animals. In a population of 20 animals
      the time to extinction is approximately 2000 years. The effects of vaccination on
      persistence were also studied, revealing that continued vaccination of the whole
      population could result in much faster eradication. For instance, in an isolated
      herd of 20 animals BHV-1 could be eradicated in 44 years.

PMID- 15724722
TI  - Correlation of IgA, IgM and IgG antibody-detecting assays based on filamentous
      haemagglutinin, pertussis toxin and Bordetella pertussis sonicate in a strictly
      adult population.
AB  - Pertussis diagnosis among adults is primarily based on serology. In this study,
      receiver operation characteristics (ROC) analysis was utilized to evaluate three
      IgA, IgM and IgG ELISAs based on B. pertussis whole-cell sonicate (WC), pertussis
      toxin (PT), or combined PT-filamentous haemagglutinin (FHA) antigens in a healthy
      adult population and in adults suffering from symptoms consistent with pertussis.
      The assays were compared to a PT and FHA reference ELISA. The reference assay
      showed high correlation with PT- and PT-FHA-based ELISAs but low correlation was
      found with the WC-based ELISA. However, ROC analysis indicated that all the
      assays enabled fine differentiation between healthy subjects and subjects
      suffering from symptoms suggestive of pertussis. The WC IgA ELISA showed the best
      diagnostic performance [highest specificity (98.8%) with highest sensitivity
      (53.8%)]. We conclude that despite a low correlation between the various assays
      they all carry good diagnostic capability for an adult population.

PMID- 15724723
TI  - The seroepidemiology of Bordetella pertussis infection in Western Europe.
AB  - High titres of pertussis toxin (PT) antibody have been shown to be predictive of
      recent infection with Bordetella pertussis. The seroprevalence of standardized
      anti-PT antibody was determined in six Western European countries between 1994
      and 1998 and related to historical surveillance and vaccine programme data.
      Standardized anti-PT titres were calculated for a series of whole-cell and
      acellular pertussis vaccine trials. For the serological surveys, high-titre sera
      (> 125 units/ml) were distributed throughout all age groups in both high- (> 90%)
      and low-coverage (< 90%) countries. High-titre sera were more likely in infants
      in countries using high-titre-producing vaccines in their primary programme
      (Italy, 11.5%; Western Germany, 13.3%; France, 4.3%; Eastern Germany, 4.0%)
      compared to other countries (The Netherlands, 0.5%; Finland, 0%). Recent
      infection was significantly more likely in adolescents (10-19 years old) and
      adults in high-coverage countries (Finland, The Netherlands, France, East
      Germany), whereas infection was more likely in children (3-9 years old) than
      adolescents in low-coverage (< 90%; Italy, West Germany, United Kingdom)
      countries. The impact and role of programmatic changes introduced after these
      surveys aimed at protecting infants from severe disease by accelerating the
      primary schedule or vaccinating older children and adolescents with booster doses
      can be evaluated with this approach.

PMID- 15724724
TI  - PspA family typing and PCR-based DNA fingerprinting with BOX A1R primer of
      pneumococci from the blood of patients in the USA with and without sickle cell
      disease.
AB  - Disease and mortality rates for Streptococcus pneumoniae infections are much
      higher in patients with sickle cell disease (SCD) than in age-matched patients
      without SCD. Pneumococcal surface protein A (PspA) has been proposed as a
      component in human vaccines against S. pneumoniae to provide greater breadth of
      coverage than can be obtained with the 7-valent conjugate vaccine. The cross
      reactivity of PspA is associated with the 'PspA family' structure. In this study
      we examined strains of S. pneumoniae from patients with and without SCD to
      determine whether the strains infecting the hypersusceptible population of SCD
      patients were limited to the same two PspA families already known to comprise
      over 95% of strains infecting non-SCD patients. Each strain was also evaluated
      according to the presence or absence of specific PCR fragments based on
      repetitive BOX elements to screen for possible SCD-associated clonal structure.
      Strains from SCD and non-SCD patients were similarly dispersed among the most
      common BOX PCR groups and strains from both groups expressed a similar
      distribution of PspA variants. Thus, a PspA vaccine designed for the population
      at large should also be appropriate for patients with SCD.

PMID- 15724725
TI  - Completion of screening for latent tuberculosis infection among immigrants.
AB  - The objective of our study was to evaluate the sociodemographic factors
      associated with completion of screening for latent tuberculosis infection (LTBI)
      among undocumented immigrants in Brescia, Italy. Screening for LTBI was offered
      to 649 immigrants; 213 (33%) immigrants completed the first step of screening;
      only 44% (55/124) of individuals with a positive tuberculin skin test result
      started treatment for LTBI. The univariate analysis showed that being unmarried,
      of Senegalese nationality and being interviewed by a health-care worker with the
      same native language as the immigrant were significantly associated with
      completion of screening for LTBI. In the multiple logistic regression, being
      interviewed in the native language of the health-care worker (OR 2.5, 95% CI 1.3
      4.8, P = 0.004) and being of Senegalese origin (OR 2.3, 95% CI 1.4-3.6, P =
      0.0005) were independently associated with adherence to LTBI screening. Our
      results suggest that knowledge of the sociodemographic characteristics of
      immigrants, and the participation of health-care workers of the same cultural
      origin as the immigrant during the visits, can be an important tool to improve
      completion of screening for LTBI.

PMID- 15724726
TI  - An outbreak of food poisoning due to a genogroup I norovirus.
AB  - Norovirus infection is associated with approximately 90% of epidemic non
      bacterial acute gastroenteritis. The objective of this study is to describe an
      outbreak of norovirus genogroup I gastroenteritis which affected workers in a
      hospital and was attributed to food prepared by an infected food handler. Forty
      cases were detected, of whom 80% were interviewed. The index case was the cook
      employed in the hospital cafeteria. The following symptoms were observed:
      abdominal pain in 90.6%, vomiting in 71.9%, diarrhoea in 71.9%, general
      indisposition in 62.5%, headaches in 53.1% and fever in 32.4% of cases. The
      initial symptoms were abdominal pain in 37% and vomiting in 28%. Of the 14
      samples analysed by RT-PCR, 12 (86%) were positive for a genogroup I norovirus.
      After sequencing the strain was identified as genotype Desert Shield. Many of the
      foodstuffs consumed were made by hand, favouring transmission from the index case
      to the cafeteria users.

PMID- 15724727
TI  - How can we increase the quality and value of clinical research?

PMID- 15724728
TI  - Glomus jugulare.

PMID- 15724729
TI  - Endoscopic view of two adjacent unilateral inferior meatal nasoantral windows.

PMID- 15724730
TI  - Truly false vocal folds: an unusual complication of chemoradiation therapy.

PMID- 15724731
TI  - Lemierre's syndrome.

PMID- 15724732
TI  - Sinonasal tract glomangiopericytoma (hemangiopericytoma).

PMID- 15724734
TI  - Normal pharyngeal and upper esophageal sphincter manometry.

PMID- 15724733
TI  - Vestibular findings in a young woman who developed dizziness and nausea following
      an airplane flight.

PMID- 15724735
TI  - Massive pleomorphic adenoma of the soft palate.

PMID- 15724736
TI  - Migraine and benign paroxysmal positional vertigo: an outcome study of 476
      patients.
AB  - To investigate whether migraine is more common in patients with benign paroxysmal
      positional vertigo (BPPV) than in the general population, the author conducted a
      retrospective study of 476 patients with BPPV seen over 12 years at a tertiary
      referral center. Records of patients with a confirmed diagnosis of BPPV followed
      for 1 to 7 years were reviewed. The typical history of BPPV and the
      characteristic torsional positional nystagmus were identified in all patients. A
      modified Epley maneuver was performed for all patients with posterior
      semicircular canal BPPV, with a 98% success rate. The survey consisted of
      detailed patient questionnaires and vestibular tests. Migraine and motion
      sickness were three times more common in patients with BPPV than in the general
      population. A family history of migraine (58.4%) and vertigo (44.9%) was also
      more common in patients than in a control group.

PMID- 15724737
TI  - The role of the middle fossa approach in the management of traumatic facial
      paralysis.
AB  - There are several controversial aspects to the management of traumatic facial
      paralysis. One of these involves the precise nature of surgical intervention once
      the decision to operate has been made. Between June 1, 1984, and June 30, 1993,
      we surgically treated 220 cases of traumatic facial paralysis with good cochlear
      reserve by decompressing the tympanic and mastoid segments via a transmastoid
      approach followed by decompression of the geniculate ganglion and the distal half
      of the labyrinthine segment via a middle fossa approach. We discuss the results
      of surgery via the middle fossa approach, and we review the literature.

PMID- 15724738
TI  - Perineural invasion of the facial nerve by a cutaneous squamous cell cancer: a
      case report.
AB  - We report a case of perineural invasion of the facial nerve by a cutaneous
      squamous cell carcinoma in a 59-year-old man who presented with a slowly
      progressive facial paralysis. We performed a distal facial nerve dissection and a
      simple mastoidectomy with facial recess exposure for resection to negative
      margins. We also performed a simultaneous facial reconstruction and reanimation
      procedure with excellent results. External-beam radiation completed the treatment
      regimen. In addition to describing this case, we review current concepts in
      diagnosis and therapy, as well as the historical background of malignant
      perineural invasion of the cranial nerves.

PMID- 15724739
TI  - Childhood primary parotid non-Hodgkin's lymphoma with direct intracranial
      extension: a case report.
AB  - Childhood primary parotid non-Hodgkin's lymphoma (NHL) is a rare but well
      recognized entity in the literature. Perineural extension of masses between the
      head and neck and cranium, although rare, has also been well documented. We
      report the first documented case, to our knowledge, of a left-sided primary
      parotid NHL in a child with direct intracranial extension through the foramen
      rotundum. The mass arose in a 1 1/2-month period. Following evaluation by
      computed tomography and magnetic resonance imaging, diagnostic procedures (first,
      fine-needle aspiration and, subsequently, an open biopsy) were undertaken. We
      discuss the case report and briefly review childhood NHL and perineural
      metastasis.

PMID- 15724740
TI  - Spontaneous bilateral intrasphenoidal lateral encephaloceles: CT and MRI
      findings.
AB  - Lateral intrasphenoidal encephaloceles are rare anomalies. We describe a unique
      case in which spontaneous bilateral intrasphenoidal lateral encephaloceles were
      discovered in a 53-year-old man during a work-up for cerebrospinal fluid leak. We
      discuss our clinical findings and the results of preoperative computed tomography
      and magnetic resonance imaging.

PMID- 15724741
TI  - Bilateral asymmetric mucoceles of the paranasal sinuses: a first case report.
AB  - Bilateral paranasal sinus mucoceles are rare. To date, only 5 cases have been
      reported in the English-language literature. All were bilaterally symmetrical. We
      present a patient with bilateral asymmetric mucoceles. This patient had a
      symptomatic mucocele of the right ethmoid sinus with orbital extension and an
      asymptomatic mucocele involving the left maxillary sinus with retroorbital
      extension. The latter was an incidental finding on radiologic evaluation. This is
      the first case report of bilateral mucoceles with asymmetric involvement of the
      paranasal sinuses.

PMID- 15724742
TI  - Bacteriology in patients with chronic sinusitis who have been medically and
      surgically treated.
AB  - Chronic sinusitis is a disease that afflicts a significant percentage of the
      population and causes considerable long-term morbidity. The common use of
      multiple broad-spectrum oral antibiotics and endoscopic sinus surgery to treat
      this condition may alter the pathogenes that promote persistence of chronic
      sinusitis. Forty-eight culture-positive patients with chronic sinusitis who had
      been medically treated for at least 3 months and had undergone sinus surgery were
      bacteriologically evaluated. Swab specimens of the middle meatus and
      sphenoethmoid recess were aseptically obtained endoscopically and cultured for
      aerobes. Coagulase-negative staphylococci were the most common isolates (45.8%),
      followed by Streptococcus pneumoniae (16.7%), Enterobacteriaceae (16.7%),
      Staphylococcus aureus (10.4%), and Pseudomonas aeruginosa (10.4%). Coagulase
      negative staphylococci were the most frequently isolated organisms in our study,
      as in many other studies. Despite the significant predominance of these
      organisms, they have always been assumed to be contaminants, and their presence
      in culture has been discounted. Coagulase-negative S aureus may be a pathogen in
      the chronic sinusitis process, and sensitivities of this isolate should be
      obtained for evaluation and possible treatment of the disease.

PMID- 15724743
TI  - Amyloid tumor of the larynx associated with plasma cell infiltration:
      differential diagnosis.
AB  - Localized amyloidosis of the larynx is uncommon, accounting for fewer than 1% of
      all benign laryngeal tumors. We report 2 cases of laryngeal amyloidosis in which
      dense plasma cell infiltrates were found in the vicinity of the amyloid deposits;
      in view of this finding, we suspected a hematologic disease--plasmacytoma in
      particular: However, molecular genetic analysis did not demonstrate any light
      chain restriction, indicating that the plasma cells were of polyclonal origin and
      therefore consistent with chronic inflammation. We also discuss the available
      literature with respect to diagnostic and therapeutic procedures in patients with
      amyloidosis of the upper airway.

PMID- 15724744
TI  - Rosai-Dorfman disease with extranodal manifestation in the head.
AB  - The term sinus histiocytosis with massive lymphadenopathy (SHML) was introduced
      by Rosai and Dorfman in 1969. Although SHML was initially described as low-pain
      cervical lymphadenopathy accompanied by fever, leukocytosis, an increased
      erythrocyte sedimentation rate, and hypergammaglobulinemia, extranodal
      involvement is observed in 25 to 40% of cases. This pathology is very rare and
      involvement of the nasal fossae and paranasal sinuses is exceptional. We present
      two atypical cases of extranodal involvement exclusively confined to the head and
      review the literature. The first case showed a dramatic involvement of facial
      skin and muscles, orbit, and paranasal sinuses. In the second case, the disease
      was limited to the nasal fossae. Both cases showed exclusive extranodal
      involvement limited to the head region. In the absence of lymphadenopathy,
      diagnosing Rosai-Dorfman disease is difficult because of the lack of the most
      typical manifestation of the disease.

PMID- 15724745
TI  - Follicular dendritic cell sarcoma of a cervical lymph node: case report and
      review of the literature.
AB  - Follicular dendritic cell sarcoma is a rare tumor that occurs mainly in lymph
      nodes. We report a case of follicular dendritic cell sarcoma in a cervical lymph
      node that was initially diagnosed as a B-cell lymphoma by Tru-Cut biopsy. The
      correct diagnosis was established by excision biopsy and immunohistochemistry.
      This tumor is of interest to head and neck surgeons because its recurrence rate
      is significant and its metastatic potential has been underestimated because of
      its rarity and the difficulty in making the diagnosis. We discuss the salient
      clinical and pathologic features of this tumor, as well as its management
      protocol, and we review the literature.

PMID- 15724746
TI  - In vitro enamel caries formation: argon laser, light-emitting diode and APF
      treatment effect.
AB  - PURPOSE: To evaluate argon laser irradiation (AL), light-emitting diode exposure
      (LED), and acidulated phosphate fluoride treatment (APF) in vitro effects on
      caries-like enamel caries formation. METHODS: Sound teeth (n = 18) were divided
      into four tooth quarters and coated with an acid-resistant varnish, leaving an
      enamel window exposed per tooth quarter. The tooth quarters were assigned to: (1)
      no treatment (control, mesiobuccal); (2) 1.23% APF (4 minutes, distolingual); (3)
      LED (Ultradent Ultra-Lume LED2 20 seconds, mesiolingual); and (4) AL (HGM Model
      8, 11.5 J/cm2, 231 mW, 5mm beam size, 10 seconds, distobuccal). Following caries
      like lesion formation (modified ten Cate solution), longitudinal sections (three
      per tooth quarter, 54 lesions per group) were obtained and evaluated for mean
      lesion depths (water imbibition, polarized light microscopy, ANOVA, DMR).
      RESULTS: Mean lesion depths were: 198 +/- 21 microm for controls; 186 +/- 17
      microm for LED; 117 +/- 19 microm for AL; and 104 +/- 23 microm for APF. Lesion
      depths were statistically significantly decreased for AL (41%) and APF (47%)
      groups (P < 0.05), compared with controls. A slight lesion depth reduction for
      LED (6%) was present compared with controls; however this was not statistically
      significantly different (P > 0.05).

PMID- 15724747
TI  - Effect of digital filtering on the measurement of the depth of proximal caries
      under different exposure conditions.
AB  - PURPOSE: To compare different image processing modes (filters) on the
      reproducibility and accuracy of the assessment of proximal carious lesions viewed
      in direct digital radiographs. Variables studied were exposure time and tissue
      scatter radiation. METHODS: Standardized direct digital radiographs of 50
      extracted teeth were obtained and 44 areas of proximal caries were detected
      histologically. Four radiographs were obtained of each tooth using a charge
      coupled device sensor. Two radiographs were obtained with and two without tissue
      scatter radiation equivalent (TSRE) each of them at normal exposure time (0.06
      second) and underexposed (0.01 second). On each of the 200 radiographs, the
      central depth (CD) of each carious lesion was measured at 21-fold magnification
      both on the unchanged image and after use of two different filters (median,
      median plus inversion). All measurements were repeated after 1 week to estimate
      reproducibility. Histometric CD assessments provided a gold standard for
      comparison with the radiographic measurements (accuracy). RESULTS: Whereas
      reproducibility was not influenced significantly by any of the investigated
      parameters, defect type and exposure time influenced the overall accuracy of CD
      measurements. Basic digital filtering of radiographic images failed to result in
      statistically significant improvement of the accuracy of CD measurements.

PMID- 15724748
TI  - Single-step, self-etch adhesives behave as permeable membranes after
      polymerization. Part III. Evidence from fluid conductance and artificial caries
      inhibition.
AB  - PURPOSE: To test the hypothesis that formation of inhibition zones by bonded
      restorations in artificially-induced carious dentin lesions is related to the
      permeability of the self-etch adhesives. METHODS: Fluid conductance of four
      single-step self-etch adhesives (Prompt L-Pop, Etch&Prime 3.0, One-Up Bond F and
      Reactmer Bond), and a control two-step self-etch adhesive (UniFil Bond) were
      measured after sound dentin surfaces were:(1) acid-etched; (2) polished to
      produce smear layers; (3) bonded with the adhesive; each at 20 cm hydrostatic
      pressure (hp). Osmotic fluid conductance was also determined for the bonded
      dentin after immersion in 4.8 M CaCl2 at 0 cm hp. For artificial caries
      inhibition, a non-fluoride releasing (NFR) two-step self-etch adhesive (UniFil
      Bond) and a fluoride-releasing (FR) single-step adhesive (Reactmer Bond) were
      used in combination with a NFR composite (Metafil CX) or a FR restorative
      material (Reactmer Paste). Artificial caries were induced in these restorations,
      from which 120 +/- 10 microm thick sections and the effect of caries inhibition
      were quantitatively assessed with polarizing light microscopy and image analysis.
      RESULTS: Fluid conductance after bonding with the single-step adhesives Prompt L
      Pop and Etch&Prime 3.0 were not significantly different from those recorded from
      smear layer-covered dentin. Although better seals were achieved with One-Up Bond
      F and Reactmer Bond, fluid conductance at 20 cm hp was significantly higher than
      the two-step self-etch adhesive UniFil Bond. Osmotic conductance at 0 cm hp were
      not significantly different from normal fluid conductance at 20 cm hp. The sizes
      of artificial carious lesions in UniFil Bond were significantly higher
      irrespective of whether a FR or NFR composite was used. Significant reduction in
      lesion size occurred in Reactmer Bond with the use of a NFR composite, and even
      more so with the use of a FR composite.

PMID- 15724749
TI  - Shear bond strength of four core materials to dentin bonded with light-cured or
      dual-cured adhesive.
AB  - PURPOSE: To measure and compare the shear bond strength of four core materials to
      dentin bonded with one adhesive (Prime and Bond NT) that was either light-cured
      or dual-cured. METHODS: The dentin of 80 freshly extracted molars was exposed
      using a series of abrasive disks. The teeth were divided into eight equal groups,
      etched with phosphoric acid for 15 seconds and rinsed. Dentin was dried to a
      moist surface. On 40 teeth, Prime and Bond NT was applied and light-cured for 30
      seconds. On 40 teeth, Prime and Bond NT was mixed with the self-cure additive,
      which was applied to the dentin, and light-cured for 20 seconds. The core
      materials were then placed following manufacturers' directions onto the cured
      adhesive. The core material was light-cured, when it was necessary, for 60
      seconds and stored for 24 hours in water at room temperature. The specimens were
      loaded in shear in the Instron until failure at a 5 mm/minute crosshead speed.
      Data were compared using two factor ANOVA and Tukey's HSD test (P = .05).
      RESULTS: Both curing mode and core material showed a significant difference. A
      significant difference between mean shear bond strength for dual and light cured
      was observed only in CompCore (P = 0.0002). There was no statistical difference
      when Prime and Bond NT dual-cured was used with chemical- or dual-cured
      materials.

PMID- 15724750
TI  - Fracture resistance of resin-based composite and ceramic inlays luted to sound
      human teeth.
AB  - PURPOSE: To assess the fracture resistance of resin-based composites (Zeta,
      Targis, Solidex,) and ceramic (Vitadur Alpha) inlays luted to extracted sound
      human premolars and classify their fracture modes. METHODS: 40 extracted sound
      human premolars were prepared to receive an indirect inlay restoration. They were
      divided into four different restorative materials groups as follows: Group A,
      Vitadur Alpha; Group B, Zeta; Group C, Targis; and Group D, Solidex. All
      restorations were luted with a resin luting cement (Opal). Specimens were loaded
      to failure in compression, and statistically analyzed (ANOVA). Fracture modes
      were recorded. RESULTS: There were no statistical differences among the four
      groups (A, 1,070 +/- 313.8 N; B, 942.4 +/- 172.4 N; C, 1,039 +/- 271.9 N; D,
      1,022 +/- 186.3 N). The predominant failure mode was a severe fracture of tooth
      and/or restoration.

PMID- 15724751
TI  - Longevity of composite restorations of traumatically injured teeth.
AB  - PURPOSE: To evaluate clinically the long-term (7-year) behavior of resin-based
      composite restorations and original fragment reattachments. METHODS: From an
      initial number of 130 young subjects (8-18 years old), only 60 fulfilled the
      inclusion criteria and consented to the evaluation of long-term follow-up of
      their restorations. Out of a total of 90 injured teeth, 70 were treated with
      direct composite restorations, and 20 with the original fragment reattachment
      technique. These 90 teeth were divided according to traditional (Andreasen,
      Ellis) classifications and according to a new classification (Spinas-Piroddi).
      Then the restorations were examined according to a modified version of USPHS
      method during the 7-year follow-up. RESULTS: Three-year old composite
      restorations needed some kind of treatment (ranging from polishing to the
      replacement of the restoration); in the period between 3-5 years, all the
      restorations (belonging to all of the injury types) needed a complete
      replacement. The results indicated that a restoration can probably be replaced
      three or four times before the tooth shows severe reduction of its adhesive
      properties. Composites cannot be used for long-term restorations; if the subject
      has completed his growth, the mandatory therapeutic alternatives are prosthetic
      restorations (crowns, porcelain veneers).

PMID- 15724752
TI  - In vitro evaluation of toothbrushing abrasion of differently bleached bovine
      enamel.
AB  - PURPOSE: To evaluate in vitro, the effect of different external bleaching agents
      on the susceptibility of enamel against toothbrushing abrasion. METHODS: 96
      bovine enamel specimens were embedded in acrylic resin, polished and covered with
      tape except for a 1.4 x 10 mm window. The samples were divided into eight groups
      (A-H), 12 specimens each (A-G) were treated with seven different home-bleaching
      (A: Whitestrips, B: Rapid White, C: Opalescence 10%, D: Opalescence PF 15%) and
      in-office-bleaching agents (E: Opalescence Extra, F: Opalescence Quick, G:
      Opalescence Extra Boost) according to manufacturers' instructions. Before and
      after each individual bleaching treatment the samples were brushed 40 times in an
      automatic brushing machine using a slurry containing artificial saliva and
      fluoridated toothpaste. The control group (Group H) was not bleached, but also
      brushed. After each cycle the specimens were stored in artificial saliva for 24
      hours. RESULTS: After 20 cycles loss of enamel was determined by profilometry,
      resulting in the following values (mean +/- standard deviation) which were
      statistically analyzed: Group A: (0.169 microm +/- 0.035), Group B (11.108 microm
      +/- 0.655), Group C (0.207 microm +/- 0.042), Group D (0.154 microm +/- 0.028),
      Group E (0.081 microm +/- 0.015), Group F (0.084 microm +/- 0.018), Group G
      (0.087 microm +/- 0.014), Group H (0.076 microm +/- 0.012). Group B differed
      significantly from the other groups (r = 0.001). Samples of Groups C, D and A
      showed a significant difference compared to the control H (r = 0.001).
      Statistical analysis revealed no significant difference between enamel loss of
      Groups E, F, G and the Control H. It could be proven that toothbrushing abrasion
      of bleached enamel may be increased depending on the bleaching agent and
      application form used. Nevertheless, with the exception of bleaching treatment
      with Rapid White, toothbrushing abrasion of bleached enamel seems to be
      clinically less relevant.

PMID- 15724754
TI  - Push-out bond strengths of tooth-colored posts bonded with different adhesive
      systems.
AB  - PURPOSE: To evaluate the effect of luting systems and root region on the push-out
      bond strengths of a glass fiber-reinforced post and a zirconia post. METHODS:
      Thirty-two extracted human anterior teeth (central incisors and canines) were
      endodontically treated with lateral condensation of gutta percha and AH26 sealer.
      Teeth were randomly assigned to eight groups (n = 4 per group). Two post systems
      from the same manufacturer (Cosmopost, a zirconia post; or FRC Postec, a glass
      fiber-reinforced post) were placed with a luting system (bonding agent and resin
      luting agent). C-Post was cemented with One-Step and Post Cement Hi-X was used as
      the light-polymerized adhesive control. ParaPost Fiber White cemented with
      ParaPost Adhesive and ParaPost Resin Cement was used as an auto-polymerized
      adhesive control. The roots were sectioned in equal thirds (apical, middle and
      cervical). A push-out test was performed in each section to measure regional bond
      strengths in MPa. Means were analyzed with two-way ANOVA and Duncan's post-hoc
      test (alpha = 0.05). RESULTS: The fiber posts ranked in the highest statistical
      subset regardless of the luting system: ParaPost Fiber White (self-cure control),
      FRC Postec bonded with Excite DSC/Variolink II, FRC Postec bonded with
      Syntac/Variolink II, FRC Postec bonded with Excite DSC/Experimental Self Cure
      Cement, and C-Post bonded with One Step/Hi-X. The zirconia post Cosmopost ranked
      in the lowest subsets regardless of the adhesive system used at P < 0.05. Means
      for the medium region of the root (5.0 +/- 0.8 MPa) were not statistically
      different from those obtained either in the cervical or in the apical region.
      Means for the cervical root region (6.2 +/- 0.9 MPa) were statistically higher
      than those of the apical region (4.5 +/- 1.1 MPa) at P < 0.001.

PMID- 15724753
TI  - Mechanical property characterization of a novel directly-placed ceramic
      restorative material.
AB  - PURPOSE: To compare, in vitro, the mechanical properties of a directly-placed
      ceramic restorative material (Doxadent) to glass-ionomer (Fuji IX), hybrid
      composite control (Z250) and amalgam control (Tytin). METHODS: Diametral tensile
      strength (DTS), compressive strength (CS), and Vickers hardness number (VHN) were
      measured for 10 specimens per group (n = 480 total) with time (1 hour, 24 hours,
      1 week, 4 weeks). CS and DTS specimens were cylinders (4 x 8 mm). VHN specimens
      were disks (9.5 x 1 mm). Specimens were prepared following manufacturers'
      instructions, stored in deionized water (37 degrees C), and tested in 100%
      humidity (23 degrees C). CS and DTS specimens were loaded to failure (Instron,
      CHS = 0.5 mm/minute). VHN discs were indented. Data were analyzed using ANOVAand
      Tukey's test (P < 0.05) for pairwise comparisons of group means at each time.
      RESULTS: In CS and DTS, DoxaDent was weakest (P < 0.05) for all testing times
      except Fuji IX DTS at 1- and 4-week intervals. For VHN, DoxaDent was harder than
      glass-ionomer, better than composite except at 1 hour and less than amalgam.
      Except for VHN for Z250, all values improved from 1-24 hours. Based on current in
      vitro results, this novel restorative material does not yet equal composite or
      amalgam CS or DTS.

PMID- 15724755
TI  - Microleakage and sealant penetration using a vibrating probe.
AB  - PURPOSE: To evaluate the effect of a vibrating probe on sealant penetration into
      pits and fissures. METHODS: Thirty-six extracted human third molars were used.
      The occlusal surface of each molar was cleaned with a rubber cup and pumice
      slurry. Scotchbond Etchant (35% phosphoric acid gel) was applied to the occlusal
      fissures of each molar for 20 seconds. Fissures were then sealed as follows:
      Group 1: Concise Light Cured White Sealant was applied without vibration; Group
      2: same as in Group 1 but with vibration; Group 3: Single Bond Adhesive was
      applied, then Concise Light Cured White Sealant was applied without vibration;
      Group 4: same as in Group 3, but sealant was applied with vibration; Group 5:
      Concise Light Cured White Sealant was applied without vibration, then Z-100
      composite was burnished over the sealant and light-cured; Group 6: same as in
      Group 5, but sealant was applied with vibration. Microvibe vibrating probe was
      used for sealant vibration. After 24-hour immersion in 2% basic fuchsin dye
      solution, specimens were sectioned, and dye and sealant penetration were scored
      using a stereomicroscope and color slides. Selected sectioned samples were
      observed under the SEM. RESULTS: No statistically significant differences between
      the groups were observed for either dye or sealant penetration scores. In all
      groups, sealant penetration was more influenced by the shape, depth and residual
      debris of fissures than by the use of a vibrating probe.

PMID- 15724757
TI  - Effectiveness of preparation guidelines for an all-ceramic restorative system.
AB  - PURPOSE: To evaluate, in a clinical field-test, the implementation of
      manufacturer's preparation guidelines for the all-ceramic CICERO system. METHODS:
      General dental practitioners from the northwest region of The Netherlands were
      asked to make complete crown preparations in accordance with the specific
      guidelines of the CICERO system. 3,446 tooth preparations were evaluated with
      regard to shoulder angle, shoulder width and top angle. They were quantified
      using a special software program. The results were compared with criteria defined
      in the manufacturer's preparation guidelines. RESULTS: On a multivariate level
      all (main and interaction) effects were significant (P < 0.05) excluding the
      interaction effect of the location of measurement on the tooth by the upper or
      lower jaw. The value of the shoulder angle showed a strong relation with the
      tooth position in the mouth as well as with the location of measurement on the
      tooth. The shoulder width in the lower jaw was significantly smaller when
      compared to the width in the upper jaw. The shoulder width of the lower incisors
      was the smallest and also showed the largest variance per tooth. On a group level
      (incisor, cuspid, premolar, molar), except for the shoulder width of the lower
      incisors, the average values of all preparation parameters were within the
      borders as defined in the preparation guidelines of the manufacturer. However, on
      an individual tooth level nearly all preparations showed to have one or more
      locations with imperfections.

PMID- 15724756
TI  - Effect of tray-based and trayless tooth whitening systems on microhardness of
      enamel surface and subsurface.
AB  - PURPOSE: To evaluate the effect of tray-based and trayless tooth whitening
      systems on surface and subsurface microhardness of human enamel. METHODS: Enamel
      slabs were obtained from recently extracted human third molars. Specimens were
      randomly assigned to six groups according to tooth whitening treatment (n = 10):
      6.0% hydrogen peroxide (HP) (Crest Whitestrips), 6.5% HP (Crest Professional
      Whitestrips), 7.5% HP (Day White Excel 3), 9.5% HP (Day White Excel 3), 10%
      carbamide peroxide (Opalescence), and a control group (untreated). Specimens were
      treated for 14 days following manufacturers' recommended protocols, and were
      immersed in artificial saliva between treatments. Enamel surface Knoop
      microhardness (KHN) was measured immediately before treatment, and at days 1, 7,
      and 14 of treatment. After treatment, subsurface microhardness was measured at
      depths of 50-500 microm. Data were analyzed for statistical significance using
      analysis of variance. RESULTS: Differences in microhardness for treated vs.
      untreated enamel surface were not statistically significant at any time interval.
      For 6.5% and 9.5% HP, there was a decrease in surface microhardness values during
      treatment, but at the end of treatment the microhardness values were not
      statistically different from the baseline values. For the enamel subsurface
      values, no differences were observed between treated vs. untreated specimens at
      each depth. Trayless and tray-based tooth whitening treatments do not
      significantly affect surface or subsurface enamel microhardness.

PMID- 15724758
TI  - Guided tissue regeneration in Class II furcation defects using a resorbable
      polylactic acid barrier.
AB  - PURPOSE: To evaluate, clinically, the use of guided tissue regeneration (GTR)
      with a resorbable polylactic acid membrane (Atrisorb) in the treatment of Class
      II furcation defects in humans. METHODS: The study included 10 patients with two
      comparable Class II furcations in lower molars. The lesions were randomly
      assigned to one of the treatments: GTR with an Atrisorb resorbable membrane
      (test) or open flap debridement (control). The following clinical parameters were
      recorded before the surgeries (baseline) and after a healing period of 6 months:
      relative vertical clinical attachment level, relative horizontal clinical
      attachment level, probing depths, position of the gingival margin and width of
      the keratinized tissue. RESULTS: After the intra-group comparison (baseline
      versus 6 months), statistically significant differences were found for the
      parameters: probing depth, relative vertical clinical attachment level and
      relative horizontal clinical attachment level, in both groups (P < 0.05).
      Comparing the two groups, a statistically significant difference was found in the
      probing depth reduction favoring the GTR group (P < 0.05). No significant
      differences were found in the other parameters.

PMID- 15724759
TI  - Influence of different dentin etching times and concentrations and air-abrasion
      technique on dentin microtensile bond strength.
AB  - PURPOSE: To determine the influence of different dentin treatments on the
      microtensile bond strengths of adhesive resins to dentin. METHODS: Fifteen human
      molars were ground to 600-grit to obtain flat root-dentin surfaces. Five
      different dentin treatments were evaluated: Group 1--10% phosphoric acid for 30
      seconds; Group 2--37% phosphoric acid for 15 seconds; Group 3--air-abrasion for
      10 seconds followed by 10% phosphoric acid for 30 seconds; Group 4--air-abasion
      for 10 seconds followed by 37% phosphoric acid for 15 seconds. The dental
      adhesive (OptiBond Solo Plus) was applied according to manufacturer's
      instructions and followed by composite (Z100) application to provide sufficient
      bulk for microtensile bond testing. All samples were placed in distilled water
      for 24 hours at 37 degrees C, thermocycled for 500 cycles in distilled water at
      10 degrees C and 50 degrees C, and serially sliced perpendicular to the adhesive
      surface and subjected to tensile forces (0.5 mm/minute). Additional samples were
      prepared for SEM to observe the adhesive interface. RESULTS: Group 2 exhibited
      significantly (P < 0.05) lower bond strength values than all other treatments.
      The bond strengths of the different conditions were (in MPa): Group 1: 43.0 +/-
      16.1; Group 2: 29.2 +/- 8.3; Group 3: 48.1 +/- 14.2; Group 4: 41.0 +/- 9.3. The
      dentin treated with phosphoric acid 37% for 15 seconds showed the lowest values
      of microtensile bond strength. The results obtained with Groups 1, 3 and 4 were
      statistically similar.

PMID- 15724760
TI  - One-year clinical evaluation of an ethanol-based and a solvent-free dentin
      adhesive.
AB  - PURPOSE: To analyze the clinical performance of adhesives with various solvents
      for restoration of non-carious cervical lesions. METHODS: The patient pool
      consisted of a total of 57 patients and 171 teeth (3 teeth per patient), with one
      non-carious cervical lesion per tooth. For each patient, one tooth was restored
      with a water-based, two-bottle adhesive (Scotchbond Multi-Purpose - SM), and
      another tooth with an ethanol-based, one-bottle adhesive (Single Bond - SB), and
      the other tooth with a solvent-free, one-bottle adhesive (One Coat Bond - OCB),
      all with resin-based composites (Silux Plus or Synergy). Restorations were
      assessed by retention, marginal integrity, margin discoloration and air
      sensitivity, according to modified USPHS criteria. The evaluations were performed
      at baseline, 6 months and 12 months after initial placement. RESULTS: The
      retention rates at 12 months were 98% for the SM adhesive, 91% for the SB
      adhesive, and 93% for the OCB adhesive. The differences in retention rates were
      not statistically significant, with 94% restorations retained overall. Measures
      of marginal integrity, marginal discoloration and sensitivity also had no
      statistically significant differences between the three adhesives. Overall, for
      the restorations still retained after 12 months, 80% had non/slightly detectable
      margins, 80% had no marginal discoloration and 90% had none/mild sensitivity. All
      three adhesives performed comparably with excellent outcomes after a 12-month
      period, with no significant differences between the water-based, ethanol-based
      and solvent-free adhesives, nor between the one-and two-bottle systems. Retention
      rate was high, air sensitivity was markedly reduced, and marginal integrity was
      good. Although superficial marginal discoloration was notable, no deep staining
      was evident. Certain lesion, tooth and patient characteristics may predispose
      restorations to retention failure.

PMID- 15724761
TI  - Curing kinetics of a photo-polymerized dental sealant.
AB  - PURPOSE: To evaluate the effect of using a variety of light-curing sources on the
      extent (monomer conversion) and rate of cure of a light-cured dental sealant.
      METHODS: Infrared spectroscopy recorded real-time polymerization of a self-cured
      and a light-cured sealant when the latter was exposed using manufacturer's
      recommendations [quartz-tungsten-halogen (QTH)] for 20 seconds as well as to
      other light sources: high intensity QTH, plasma arc light (PAC), and second
      generation blue light emitting diode (LED) units. Specimens were heated to 37
      degrees C and the degree and rate of conversion were recorded at each second for
      300 seconds. Conversion extent and rate were compared among light units as well
      as to the self-curing product. Five replications for each test condition were
      performed. RESULTS: After 300 seconds, self-curing product conversion was
      equivalent to all light-exposed specimens. The self-cured rate of cure was
      significantly lower than all light-cured scenarios. The high intensity QTH light
      provided equivalent conversion as conventional 20-second QTH exposure (control)
      in only 10 seconds. The PAC light required similar exposure time as conventional
      QTH treatment. Second-generation blue LED units reached conversion similar to
      control in only 10 seconds, while one light required only 5 seconds' exposure.

PMID- 15724762
TI  - Potential remineralization of demineralized enamel after application of fluoride
      varnish.
AB  - PURPOSE: To evaluate remineralization effects of a topical fluoride varnish
      applied over a caries-like lesion compared to around a caries-like lesion.
      METHODS: Caries-like lesions were created on 30 molar surfaces. Sections were cut
      through each lesion, photographed under polarized light microscopy, and
      quantitated with a computerized imaging system. The sections were repositioned
      with only the lesion exposed. Half were painted with a 5% NaF varnish, including
      the surface of lesion. The remaining half were painted excluding the surface of
      the lesion. The sections were placed in artificial saliva for 30 days, re
      photographed and re-quantitated. RESULTS: Using a student t-test for analysis,
      the results demonstrated the mean (+/- S.E.) percent remineralization of lesion
      size to be 10.8 (4.8) for lesions completely covered by the fluoridated varnish
      and 9.5 (2.9) for lesions that had the fluoridated varnish surrounding the
      lesion. Both application techniques indicated remineralization effects, yet there
      was no significant difference between the two application techniques evaluated in
      this study (P < 0.05). The data from this in vitro study indicated that there was
      no significant difference in methods of application for fluoridated varnish. Both
      application techniques demonstrated effective remineralization.

PMID- 15724763
TI  - Racial differences in mortality from obesity-related chronic diseases in US women
      diagnosed with breast cancer.
AB  - OBJECTIVE: Previous studies have focused on racial differences in cancer-specific
      mortality among US women diagnosed with breast cancer. In view of rising
      prevalence rates of obesity and persistent racial differences in obesity in the
      United States, this study considered risk of death from obesity-related causes.
      METHODS: For 233,329 women diagnosed with invasive breast cancer in 9 SEER areas
      in 1975-1995, all with at least 5 years of potential follow-up after diagnosis,
      Cox proportional hazards regression was used to analyze relative risks (RRs) of
      death (underlying cause) from 4 obesity-related chronic diseases (diabetes
      mellitus, hypertension, coronary heart disease or CHD, and cerebrovascular
      disease) for "White," "African-American," and "Asian-American" patients. RESULTS:
      RRs were statistically significantly higher for African Americans vs Whites for
      the 4 obesity-related causes, and for diabetes in Asian Americans vs Whites.
      CONCLUSIONS: Interventions must be designed to address these racial disparities
      among women diagnosed with breast cancer.

PMID- 15724764
TI  - "I will miss the study, God bless you all": participation in a nutritional
      chemoprevention trial.
AB  - Randomized controlled clinical trials are often considered to be the "gold
      standard" for health research. Consequently, understanding the reasons people
      participate in these trials, especially minority groups who are often under
      represented in clinical trials, or populations who have chronic illnesses or
      abuse drugs, is salient for successful recruitment, retention, and project
      design. This paper describes the results of a study that was designed to examine
      some of the ways in which participants in a randomized double blind clinical
      trial perceived their participation in the clinical trial, and the reasons they
      gave for continuing in the study. All of the participants were individuals who
      were using drugs and were infected with the HIV-1 virus, and had participated in
      a chemoprevention trial. The data from an exit interview were analyzed
      thematically in order to reveal units of meaning concerning participation and
      continuation in the clinical trial. The analysis revealed 3 higher-level
      concepts, or themes, that guided participation: increased health awareness,
      personal enhancement, and sociability. The data clearly indicated that
      involvement and retention in the trial were directly related to the ways in which
      the participants interpreted the study, perceived the benefits they derived from
      participating, and imbued their participation with value so that it was important
      and relevant to their own perceptions of health, as well as personal and social
      well being.

PMID- 15724765
TI  - Serum total homocysteine concentration determinants in non-Hispanic White, non
      Hispanic Black, and Mexican-American populations of the United States.
AB  - OBJECTIVE: Blood vitamins and the association between serum total homocysteine
      (tHcy) concentration and demographic, socioeconomic, health and lifestyle factors
      were investigated in non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and
      Mexican Americans (MA). DESIGN AND SETTING: Cross-sectional data from the third
      National Health and Nutrition Examination Survey, 1988-1994, was used.
      PARTICIPANTS: The study included 2,258 NHW, 1,856 NHB, and 1,584 MA. MAIN OUTCOME
      MEASURES: Relationship between serum tHcy (dependant variable), and sex, age,
      income, education, alcohol consumption, vitamin/mineral supplement and medicine
      use, body mass index (BMI), systolic and diastolic blood pressures, serum
      creatinine, cotinine (a measure of smoking), folate and cobalamin, and red blood
      cell (RBC) folate (independent variables) was analyzed with multivariate analysis
      of covariance and linear regression. RESULTS: Serum tHcy was significantly higher
      in NHW and NHB than in MA. Serum and RBC folate were significantly higher and
      serum cobalamin was significantly lower in NHW compared to their counterparts.
      Serum folate and serum creatinine were the strongest determinants of tHcy in NHB
      and MA, and in NHW, respectively. The BMI was negatively associated with tHcy in
      NHB (P=.02) and in MA (P=.002) but not in NHW. Systolic blood pressure and serum
      cotinine were positively associated with tHcy only in NHW and MA. Education,
      income, supplement and medicine use, and alcohol consumption were not associated
      with tHcy concentration in any race-ethnicities. CONCLUSIONS: In this large
      population based study, regardless of race-ethnicity, age, serum creatinine,
      folate, and cobalamin, and RBC folate were the major determinants of serum tHcy.

PMID- 15724766
TI  - Left ventricular structure and systolic function in African Americans: the
      Atherosclerosis Risk in Communities (ARIC) study.
AB  - OBJECTIVES: To estimate prevalence of left ventricular (LV) hypertrophy and its
      relation to systolic function in a population-based sample of African Americans.
      DESIGN: A baseline 2D guided M-mode echocardiogram was conducted as part of a
      longitudinal cohort study to assess prevalence and cross-sectional relationships
      between echocardiographic and clinical parameters. SETTING: Data were collected
      as part of the Atherosclerosis Risk in Communities study. PARTICIPANTS: Analysis
      is limited to 1543 African Americans, aged 51-70 years, without clinically
      apparent cardiovascular or echocardiographically determined valvular disease.
      MAIN OUTCOME MEASURES: LV hypertrophy prevalence was defined as LV mass/
      height2.7 > or = 51 g/m2.7. LV systolic chamber function was assessed at the
      midwall using the ratio of observed midwall fractional shortening (MWS%) to the
      value predicted from circumferential end-systolic stress. RESULTS: The prevalence
      of LV hypertrophy was 33% in men, 38% in women. The prevalence of concentric
      hypertrophy (LV hypertrophy with relative wall thickness > or = 0.45) was greater
      than that of eccentric hypertrophy (men: 24% vs 9%; women: 27% vs 11% women).
      Observed/predicted (O/P) MWS% was strongly and inversely related to LV mass/
      height2.7 (P<.001) and LV hypertrophy (P<.001). The O/P MWS% was inversely
      related to LV mass/height2.7 quartile: O/P MWS% was 106% and 99% in the first and
      97% and 89% in the fourth quartile of LV mass/height2.7 for men and women,
      respectively. Adjusting for age, adiposity, diabetes, blood pressure,
      antihypertensive medication use, and smoking did not remove association between
      O/P MWS% and LV mass/height2.7. CONCLUSIONS: LV hypertrophy was highly prevalent
      in this population-based middle-aged sample of African Americans and was
      associated with poorer LV systolic chamber function.

PMID- 15724767
TI  - Does socioeconomic position moderate the effects of race on cardiovascular
      disease mortality?
AB  - OBJECTIVE: Cardiovascular disease (CVD) rates differ markedly by minority status,
      with younger Blacks having some of the highest CVD mortality rates in the United
      States. A major objective of this study was to assess whether socioeconomic
      position moderates the effects of race or minority status on CVD mortality.
      DESIGN: The sample included 443 Black and 21,182 White men, and 415 Black and
      24,929 White women, 45 years and older, who died of CVD from 1992-1998, and who
      had lived in the Twin Cities 5-county area. Using individual and neighborhood
      level measures of socioeconomic position, we hypothesized that socioeconomic
      position would moderate the effects of race on CVD mortality. Test hypotheses
      were analyzed using Poisson regression analysis. RESULTS: Socioeconomic position
      moderated the effects of race on CVD mortality among older men, but not in older
      women. Older Black men who lived in more impoverished neighborhoods had
      significantly and disproportionately higher CVD mortality rates than did older
      White men living in more impoverished neighborhoods; this was not the case among
      older Black and White men living in less impoverished neighborhoods. Race was
      independently related to CVD mortality among younger men and women, with younger
      Black men and women having significantly higher CVD mortality rates than younger
      White men and women. The Black-White rate for Black women was twice that of White
      women. CONCLUSION: Socioeconomic position as measured by neighborhood poverty can
      moderate the effects of race on CVD mortality in older Black and White men. This
      may not have been as apparent had socioeconomic position not been treated as a
      major variable of interest, and measured at multiple levels.

PMID- 15724768
TI  - Knowledge and practice: the risk of cardiovascular disease among Asian Indians.
      Results from focus groups conducted in Asian Indian communities in Northern
      California.
AB  - OBJECTIVE: The focus groups were utilized to gather information on the
      perceptions of cardiovascular risk within the Asian Indian community, and to
      identify opportunities to design health promotion and intervention programs for
      Asian Indian communities. DESIGN: Qualitative methods were utilized to obtain
      perceptions of cardiovascular risk within 3 Asian Indian communities. Eight focus
      groups were conducted in either English or Punjabi. SETTING: These focus groups
      were conducted as part of a 3-year community-based participatory research project
      examining cardiovascular risk factors among the Asian Indian population in
      Northern California. PARTICIPANTS: Focus group participants were selected through
      referrals from community-based organizations, postings in local community
      centers, and businesses. Fifty-seven men and women were recruited using snowball
      sampling. RESULTS: Six themes emerged from the focus groups: knowledge of
      cardiovascular disease, health and cultural concerns regarding diet, physical
      activity levels, stress as a factor for cardiovascular disease, acculturation
      concerns, and cardiovascular prevention ideas. CONCLUSIONS: The use of focus
      groups was an effective method for gathering information on perceptions of
      cardiovascular risk, and collecting information on risk behaviors within these
      Asian Indian communities. In this study, we found that psychosocial and cultural
      factors, especially cultural issues concerning stress and acculturation, surfaced
      as key elements across all 8 focus groups.

PMID- 15724769
TI  - Association of a culturally defined syndrome (nervios) with chest pain and DSM-IV
      affective disorders in Hispanic patients referred for cardiac stress testing.
AB  - BACKGROUND: Hispanics have a high prevalence of cardiovascular risk factors, most
      notably type 2 diabetes. However, in a large public hospital in Houston, Texas,
      Hispanic patients referred for cardiac stress testing were significantly more
      likely to have normal test results than were Whites or non-Hispanic Blacks. We
      undertook an exploratory study to determine if nervios, a culturally based
      syndrome that shares similarities with both panic disorder and anginal symptoms,
      is sufficiently prevalent among Hispanics referred for cardiac testing to be
      considered as a possible explanation for the high probability of a normal test
      result. METHODS: Hispanic patients were recruited consecutively when they
      presented for a cardiac stress test. A bilingual interviewer administered a brief
      medical history, the Rose Angina Questionnaire (RAQ), a questionnaire to assess a
      history of nervios and associated symptoms, and the PRIME-MD, a validated brief
      questionnaire to diagnose DSM-IV defined affective disorders. RESULTS: The
      average age of the 114 participants (38 men and 76 women) was 57 years, and the
      average educational attainment was 7 years. Overall, 50% of participants reported
      a history of chronic nervios, and 14% reported an acute subtype known as ataque
      de nervios. Only 2% of patients had DSM-IV defined panic disorder, and 59% of
      patients had a positive RAQ score (ie, Rose questionnaire angina). The acute
      subtype, ataque de nervios, but not chronic nervios, was related to an increased
      probability of having Rose questionnaire angina (P=.006). Adjusted for
      covariates, a positive history of chronic nervios, but not Rose questionnaire
      angina, was significantly associated with a normal cardiac test result (OR=2.97,
      P=.04). CONCLUSION: Nervios is common among Hispanics with symptoms of cardiac
      disease. Additional research is needed to understand how nervios symptoms differ
      from chest pain in Hispanics and the role of nervios in referral for cardiac
      workup by primary care providers and emergency room personnel.

PMID- 15724770
TI  - Coronary artery disease and risk factors in Black South Africans--a comparative
      study.
AB  - OBJECTIVE: The purpose of this study was to identify and compare coronary risk
      factors in different South African ethnic groups with angiographically documented
      significant coronary artery disease (CAD). DESIGN: An observational retrospective
      analysis. METHODS: Hospital records of 500 consecutive patients with no previous
      coronary interventions who underwent coronary angiography at Chris Hani
      Baragwanath Hospital, Soweto over a 2-year period were reviewed. Patients with
      significant CAD were selected for this study. Data analyzed included
      demographics, presenting diagnoses, coronary risk factors, number of coronary
      arteries significantly affected and extent of CAD, left ventricular ejection
      fraction (LVEF), and the main treatment modality for CAD. RESULTS: Of the 206
      patients with significant CAD, 85 were Africans and 121 were non-Africans. There
      were significantly more females in the African group (31% vs 12%, P=.0023) and
      hypertension was more prevalent in the same group (78% vs 55%, P=.0006). Serum
      total (TC) and low-density lipoprotein (LDL) cholesterol were significantly lower
      in African than in non-African patients [189.5 (96.67-313.2) vs 228.2 (127.6-464)
      mg/dL; P=.0006 and 100.5 (34.8-282.3) vs 146.9 (42.54-313.2) mg/dL; P=.0001,
      respectively]. CONCLUSION: Cholesterol levels in this group of African patients
      with angiographically significant CAD are within the target range recommended by
      the adult treatment panel III (ATP III) guidelines of the National Cholesterol
      Education Program (NCEP). These data have implications for risk assessment using
      cholesterol and the role of cholesterol lowering treatment in populations of
      developing countries.

PMID- 15724771
TI  - Designing multi-ethnic stroke studies: the Brain Attack Surveillance in Corpus
      Christi (BASIC) project.
AB  - The Brain Attack Surveillance in Corpus Christi (BASIC) project is a population
      based stroke study comparing Mexican Americans and non-Hispanic whites. Extensive
      effort is made to detect all patients regardless of ethnicity and ensure equal
      participation in the interview among both groups. We describe here the study's
      design and process evaluation with a focus on reducing bias in case ascertainment
      and participation. During the first 28 months of the project, 11,829 subjects
      were screened. Availability of neuroimaging did not differ by ethnicity (P=0.22),
      nor did confidence in the validated diagnosis of stroke (P=0.10). Participation
      rate in the interview also did not differ by ethnicity (P=0.92). There was
      excellent agreement of ethnic classification between chart abstraction and self
      report (kappa=0.94, P<0.001). We conclude that multi-ethnic stroke comparison
      studies are feasible. Utilizing epidemiologic principles to design, recruit and
      analyze data are critical. Process evaluation to examine for sources of bias is
      important to study conduct.

PMID- 15724772
TI  - Dietary behavior among African Americans: assessing cultural identity and health
      consciousness.
AB  - The present study utilized the African self-consciousness (ASC) construct as an
      index of African-American cultural identity, and explored its association .with
      health consciousness and dietary behavior. One hundred ninety-seven African
      American adults residing in a Southeastern community participated in the study.
      Results demonstrated few, but significant, correlations between cultural identity
      and health consciousness. A similar relationship was observed between cultural
      identity and dietary behavior. Further, after statistically controlling for
      health consciousness, cultural identity contributed unique variance to dietary
      behavior. These findings represent preliminary evidence suggesting the general
      viability of cultural models in explaining African-American health behavior. More
      importantly, the study offers avenues for additional research on the complex
      roles played by culture and cultural identity in African-American dietary
      behavior.

PMID- 15724773
TI  - "Does skinny mean healthy?" Perceived ideal, current, and healthy body sizes
      among African-American girls and their female caregivers.
AB  - OBJECTIVES: To qualitatively and quantitatively examine body image ideals and
      perceived weight-related health among African-American girls and their female
      caregivers to inform intervention development for Girls Rule!, an obesity
      prevention pilot program. DESIGN, SETTING, AND PARTICIPANTS: Formative study
      using qualitative data from semi-structured interviews and validated quantitative
      body image silhouette assessment among girls (N=47) and caregivers (N=44). The
      participants were a convenience sample of African-American church members from
      North Carolina. Differences were evaluated between perceived: 1) current and
      ideal body size; 2) current and unhealthy body size; and 3) ideal and unhealthy
      body size. RESULTS: Thirty-seven percent of the girls and 77% of the caregivers
      were overweight or obese. Three body image themes emerged from the qualitative
      interviews: 1) being fat is unhealthy; 2) caregivers are role models (positive
      and negative) for body image ideals; and 3) smaller body size is important for
      wearing fashionable clothing. A series of 9 body silhouettes were used to assess
      perceptions of both girls and caregivers. Overall, both girls (2.9 +/- 1.4) and
      caregivers (4.4 +/- 1.4) ideal body size was significantly (P<.01) smaller than
      their current body size (3.7 +/- 1.3 girls; 6.3 +/- 2.2 caregivers). Both girls
      (3.7 +/- 1.4) and caregivers (6.7 +/- 2.0) indicated that their current body
      sizes were statistically significantly (P<.05) smaller that what they considered
      to be unhealthy (7.9 +/- 1.4 girls; 7.9 +/- 1.2 caregivers). CONCLUSIONS: Results
      suggest that most of these African-American participants were not satisfied with
      their current body size and desired a smaller body. At the same time, both girls
      and caregivers failed to recognize the potential health consequences associated
      with their current body size. Critical issues for designing obesity prevention
      programs include positive role modeling within the family and addressing the
      association of body size with health risk.

PMID- 15724774
TI  - Overweight and obesity among urban Sahraoui women of South Morocco.
AB  - OBJECTIVES: To estimate the prevalence of obesity in Moroccan Sahraoui women; to
      describe their distribution of body fat; and to examine the influence of age,
      calorie intake, physical activity, marital status, education level, and desire to
      lose weight on obesity. DESIGN: Randomized samples of adult women who visited the
      public health centers during a immunization campaign period. PARTICIPANTS: Data
      were obtained on 249 non-pregnant urban women aged 15 and older, who live in the
      city of Laayoune in South Morocco. Only subjects identified as Sahraoui origin
      were eligible for this investigation. MAIN OUTCOME MEASURE: The following data
      were collected: body weight, height, circumference of waist and hip, calorie
      intake, physical activity, marital status, education level, and desire to lose
      weight. RESULTS: The overall prevalence of overweight and obesity was 30% and
      49%, respectively, and was found to be very high in younger age groups. The
      prevalence of abdominal obesity was also high and increased with age. Sixty-eight
      percent of women had a waist-to-hip ratio (WHR) > 0.85 and 76% had a waist
      circumference (WC) > or = 88. The calorie intake, the time spent in a walking
      activity, and the time spent in traditional sedentary occupation were associated
      with obesity. The prevalence of obesity was higher among married women compare to
      unmarried women and was not influenced by education level. A very small
      percentage of the female population expressed a desire to lose weight.
      CONCLUSION: High prevalence of obesity, even in young adult women, needs
      immediate attention in terms of prevention and health education among the urban
      Sahraoui women.

PMID- 15724775
TI  - A randomized pilot trial of exercise promotion in sedentary African-American
      adults.
AB  - This study compared the effects of 3 home-based exercise promotion programs for
      African Americans. Sixty, sedentary African-American adults were randomly
      assigned to either a standard behavioral counseling group (N=22), a culturally
      sensitive counseling group (N=20), or a physician advice comparison group (N=10).
      The key study outcomes measured at baseline and after 6 months included
      cardiorespiratory fitness and physical activity. Acculturation was examined as a
      moderating variable. Participants in all 3 groups reported significant increases
      in walking, but significant improvements in fitness were observed only in the 2
      intervention groups. Participants in the culturally sensitive intervention
      reported significantly higher levels of exercise social support compared to
      members of the other 2 groups. These findings show that home-based exercise
      counseling programs are effective for improving fitness, yet the addition of
      culturally tailored components may not be sufficient to produce better outcomes
      than standard behavioral counseling.

PMID- 15724776
TI  - Racial and ethnic differences in osteoarthritis: prevalence, outcomes, and
      medical care.
AB  - Osteoarthritis (OA) is the most common chronic condition and a leading cause of
      disability among older adults. Studies indicate there are important racial and
      ethnic differences in the prevalence of OA, as well as in the associated outcomes
      and medical care. In general, research suggests some minority groups, especially
      African-American and Hispanic individuals, may be at risk for poorer outcomes
      (such as pain and disability), and are less likely to undergo arthroplasty,
      compared to Caucasian Americans. Racial and ethnic differences in OA and its
      medical care are poorly understood. Research is needed to examine biological,
      psychosocial, and lifestyle factors that may contribute to these disparities.

PMID- 15724777
TI  - Physician-patient interaction and depression among African-American women: a
      national study.
AB  - OBJECTIVE: To examine the relationship between physician-patient interaction and
      depression among African-American women. DESIGN: Cross-sectional survey.
      PARTICIPANTS: 1,411 African-American women completed a mailed 46-item survey on
      psychological well-being. MAIN OUTCOME MEASURES: The independent variables
      included demographics and depressive symptomatology as measured by the CES-D. The
      dependent variable was the mean score on an 8-item measure of physician-patient
      interaction, and other factors associated with physician-patient interaction.
      RESULTS: Overall, even after accounting for demographic variables, the higher
      scores on the CES-D were associated with lower scores on physician-patient
      interaction (B=1.11, 95% CI=1.06, 1.16). Depression was positively associated
      with: difficulty in talking to physicians, likelihood of discussing problems with
      physicians, reporting that a physician had made offensive comments, and the
      likelihood of changing physicians due to dissatisfaction (all P values <.01).
      CONCLUSIONS: These results suggest that depressive symptomatology may be an
      important factor to consider in physicians' interaction with African-American
      women.

PMID- 15724778
TI  - Diabetes care among older urban American Indians and Alaska Natives.
AB  - OBJECTIVE: To assess the prevalence of, and quality of care for, diabetes
      mellitus among the understudied, yet growing, population of older, urban American
      Indians and Alaska Natives (AI/ANs). DESIGN: Medical record review. SETTING:
      Urban Indian primary care clinic in Seattle, Washington. PATIENTS: All (N = 550)
      AI/AN patients > or = 50 years of age. MAIN OUTCOMES MEASURES: Provider
      documented medical diagnoses and indicators of quality of care of diabetes.
      RESULTS: Diabetes mellitus was documented in 113 (21%) of the medical records.
      Persons with diabetes were more likely than those without (P > or = .05) to be
      obese, and to have hypertension, coronary artery disease, and depression. Most
      patients with diabetes were treated with either insulin (43%) or oral
      hypoglycemic medication (39%), but 16% received neither. Screening rates within
      12 months were high for glycosylated hemoglobin (72%), lipid profile (84%), and
      foot examination (72%), but were low for urinalysis (23%), ophthalmology referral
      (23%), and influenza vaccination (46%). Only 46% of patients had ever received
      pneumococcal vaccination, and even fewer (26%) had received tuberculin skin
      testing (24%). Although 65% of patients had ever been referred to a dietitian,
      only 40% had received exercise counseling. The total number of health problems
      was the factor most often associated with quality of care indicators.
      CONCLUSIONS: The prevalence rate of diabetes among this urban clinic population
      of older AI/ANs was high. Although performance of quality indicators was
      suboptimal, it was comparable to, or better than, that found in other older
      populations for many measures.

PMID- 15724779
TI  - Racial and ethnic variation in response to mailed and telephone surveys among
      women in a managed care population.
AB  - PURPOSE: To describe the characteristics of participants who completed a mailed
      survey, compared to those initial non-responders who completed the same survey
      over the telephone. STUDY DESIGN AND PATIENT POPULATIONS: We conducted a mailed
      survey, in both Spanish and English, among women with abnormal Pap smears, who
      were members of a large managed care organization. Telephone follow up for non
      responders was performed by a bilingual interviewer. A 20-minute long distance
      telephone card was offered as an incentive to individuals who completed the
      telephone survey. We used bivariate and multivariate analyses to describe the
      population characteristics of respondents who replied by mail, as compared to
      those who completed the survey by telephone. RESULTS: Of the 1049 potentially
      eligible participants, 733 women completed the survey, for an overall response
      rate of 70%. Fifty-six percent (N=411) of the surveys were received by mail, and
      44% (N=322) were completed by telephone. Thirty-four percent of the telephone
      surveys were completed in Spanish, compared to 13% of the mailed surveys
      (P<.001). Telephone respondents were less satisfied with their health care than
      were those who responded by mail. CONCLUSIONS: Among this insured cohort of
      women, Latinas who completed the survey in Spanish were more likely to
      participate in a telephone survey that offered an incentive, than in a mailed
      survey. These findings should be considered when planning health surveys in this
      population.

PMID- 15724780
TI  - A community study of language concordance in Russian patients with diabetes.
AB  - PURPOSE: Unique challenges exist in the provision of culturally and
      linguistically appropriate health care to ethnically diverse populations. The
      purpose of this study was to improve the metabolic control of Russian patients
      with diabetes through increased attention to language and cultural concordance
      between the provider and patient. PROCEDURES: This is a retrospective cohort
      study of 55 Russian immigrant type 2 patients with diabetes to assess levels of
      glycemic, lipid, and blood pressure control before and after the arrival of a
      bilingual Russian internist trained in both the United States and Russia. Paired
      t test was used to compare these parameters before and after the bilingual
      Russian provider joined our practice. FINDINGS: Overall, the mean low density
      lipoprotein (LDL) level decreased by 20% from 126 mg/dL to 102 mg/dL (P=.0002)
      respectively before and after the Russian provider began treating these patients.
      Mean hemoglobin A1c decreased from 8.4% to 8.0% (P=.007), and diastolic blood
      pressure was reduced from 82.7 mm Hg to 76.3 mm Hg (P=.0002). Systolic blood
      pressure also improved from 143.2 mm Hg to 140.6 mm Hg (P=.3). At the end of the
      study period more than 90% of the patients with diabetes were appropriately
      taking lipid-lowering medications and an angiotensin converting enzyme (ACE)
      inhibitor. CONCLUSION: Our findings suggest that it is important to facilitate
      the health care of ethnically diverse minority populations in a manner that
      attempts to maximize language and cultural concordance. These potential benefits
      will assume an even greater importance with the expansive growth of ethnic
      minorities in the United States and their unique healthcare needs.

PMID- 15724782
TI  - Treating osteoarthritis--are all populations receiving equal care?

PMID- 15724781
TI  - Explaining the relationship between race/ethnicity and pharmacy purchased
      syringes among injection drug users in New York City.
AB  - OBJECTIVE: Pharmacy syringe sales without a prescription became legal in New York
      State on January 1, 2001 through the Expanded Syringe Access Demonstration
      Program (ESAP). At the same time, Pharmacy use among Black and Hispanic injection
      drug users was found to be significantly lower when compared to Whites. The
      purpose of this study was to assess the factors that could explain the
      relationship between race/ethnicity and pharmacy use. DESIGN: Data were combined
      from 2 on-going injection drug user (IDU) studies in 2 New York City
      neighborhoods. Social and behavioral factors independently associated with ever
      purchasing a nonprescription syringe in the past 6 months and examined using
      cross-sectional logistic regression. RESULTS: Of 337 IDUs, the majority were male
      (79%), Hispanic (73%) and had a mean age of 35 years. In bivariate analysis, IDUs
      who reported pharmacy use were less likely to be Black or Hispanic, older, and to
      have reported recent syringe exchange program (SEP) attendance compared to non
      pharmacy users. Additionally, pharmacy users were more likely to have knowledge
      of ESAP, and report discrimination by police in the past year compared to non
      users. After adjustment for recent SEP attendance (adjusted odds ratio
      [AOR]=0.27; 95% confidence interval [CI]=0.14-0.55), ESAP knowledge (AOR=13.11;
      95% CI=6.54-26.31), discrimination by police (AOR=3.56; 95% CI=1.73-7.35), and
      discrimination due to race (AOR=0.25, 95% CI=0.11-0.58), race/ethnicity was not a
      significant predictor of pharmacy use. CONCLUSIONS: Race/ethnicity may not be an
      important determinant of ESAP when more salient social circumstances, such as
      past discrimination, are considered. Educational efforts should be enhanced to
      reach those who continue to perceive barriers to ESAP.

PMID- 15724783
TI  - Patients in clinical trial report benefits to participation.

PMID- 15724784
TI  - Doctors urged to talk with African-American women who suffer from depression.

PMID- 15724785
TI  - Obesity rates and quality of treatment may lead to higher obesity-related deaths
      among African-American women with breast cancer.

PMID- 15724786
TI  - Heart disease and cholesterol levels among Africans puzzle researchers.

PMID- 15724787
TI  - Indian health diabetes program found to be effective.

PMID- 15724788
TI  - Study findings show more cases of stroke than expected; points to need to
      recognize stroke symptoms.

PMID- 15724789
TI  - Therapeutic controversies in hypertension management: angiotensin converting
      enzyme (ACE) inhibitors or angiotensin receptor blockers in diabetic nephropathy?
      ACE inhibitors.
AB  - Diabetic nephropathy is the number one cause of endstage renal disease in the
      United States. Blood pressure is most important in delaying the progression of
      renal disease in persons with diabetes and, agents that block the renin
      angiotensin system (RAS) should be the primary agents used to achieve blood
      pressure reduction. There is debate regarding which method of RAS blockade should
      be used as primary therapy in persons with diabetes. There are not significant
      differences between angiotensin converting enzyme (ACE) inhibitors and
      angiotensin receptor blockers (ARBs) with regard to renal outcomes. Consideration
      of the enormously high rates of cardiovascular disease (CVD) in persons with
      diabetes and renal disease is the primary factor in choosing agents for blood
      pressure reduction. The ACE inhibitors and ARBs have been shown to reduce
      cardiovascular events in persons with diabetes and, there are recent comparable
      trials between the 2 classes. Some studies and meta-analyses show ACE inhibitors
      as being superior with regard to cardioprotection. In our nephrology clinic, we
      find that patients who presented on an ACE inhibitor had significantly lower CVD
      than those on ARBs (49.2% vs 70.1% prevalence of CVD, ACE inhibitor vs ARB
      respectively, P=.042). We conclude that ACE inhibitors should be strongly
      considered as the primary method of RAS inhibition in persons with diabetes.

PMID- 15724790
TI  - Increasing physical activity in the deconditioned person: the role of resistance
      training.

PMID- 15724791
TI  - Genetics and cardiovascular disease.
AB  - Cardiovascular disease (CVD) is a designation for multiple clinical phenotypes
      that result from the interaction of genetic variants, lifestyle choices, and
      environmental exposures. This article points to the utility of assessing a
      person's family history of CVD, which is the sum of genetic factors, environment
      and common lifestyle influences, which may be shared among family members and
      provides information useful for estimating risk for CVD. It also presents several
      approaches utilized in attempts to identify variants in genes that are involved
      in the etiology of CVD. Specifically, examples of the candidate gene approach to
      identify genetic risk factors for coronary heart disease from our own research
      are presented. The utilization of genetic profiling to predict an individual's
      long-term prognosis, to target preventive strategies, and to select the most
      efficacious drug for treatment are discussed, as well as, the need to consider
      newer approaches to understanding complex diseases.

PMID- 15724792
TI  - Theoretical perspectives to increase clinical effectiveness of lifestyle
      modification strategies in diabetes.
AB  - Diabetes affects more than 18 million people in the United States. The prevalence
      of type 2 diabetes has increased at an alarming rate in the past 20 years.
      Minorities are disproportionately affected, with the greatest increase in adult
      prevalence noted in African-American women. The increasing prevalence of type 2
      diabetes in both children and adults is strongly associated with the increasing
      prevalence of obesity. Diabetes and its complications can be controlled with
      appropriate health care and patient self-management techniques. There is strong
      empirical evidence supporting the efficacy of dietary and physical activity
      interventions in the prevention and treatment of type 2 diabetes. The results of
      empirical studies have not translated well into clinical practice. Four key
      theoretical concepts are presented in an effort to increase the effectiveness of
      lifestyle intervention counseling by primary care providers. The four concepts
      include: perceptual congruence, mutual goal setting, readiness to change, and
      tailored interventions.

PMID- 15724793
TI  - Hypertension: trends, risks, drug therapies and clinical challenges in African
      Americans.
AB  - In the United States, cardiovascular disease (CVD) is the leading killer
      accounting for about 1 million fatalities annually, with hypertension being a
      major risk factor for stroke, coronary heart disease (CHD), cardiovascular (CV)
      death, heart failure, and end-stage renal disease--all of which have higher
      prevalence in African Americans, who also experience greater severity at clinical
      presentation. In numerous randomized trials and meta-analyses, drug therapy for
      hypertension has been shown to reduce blood pressure by 4-6 millimeters of
      mercury (mm Hg) with resultant decreases in stroke of 35%-40%, CHD of 20%-25%,
      and CV death of about 25%. Cardiovascular drug therapies of proven benefit,
      including diuretics, angiotensin converting enzyme (ACE inhibitors), and beta
      blockers, are safe and effective, alone and in combination. Since African
      Americans with hypertension tend to have a more severe presentation, they will be
      even more likely to require multiple drug therapies, which also will include
      diuretics and calcium channel blockers. Effective strategies to encourage
      widespread use of these therapies of proven benefit would provide progress toward
      decreasing the adverse mortality experiences, especially CVD, among African
      Americans.

PMID- 15724794
TI  - Metabolic syndrome: implications of race and ethnicity.
AB  - Many of the studies evaluating implications of the metabolic syndrome have not
      looked specifically at varied ethnic groups to compare and contrast the effects
      of ethnicity on the metabolic syndrome. Most of the data regarding ethnicity
      comes from cross sectional studies of national data bases such as NHANES. Other
      studies seem to have lower numbers of ethnic groups other than Caucasians. For
      clinical practice, most of the data may be extrapolated until data from
      randomized prospective trials are available. Certainly it would appear that many
      of the cardiovascular implications persist when adjusted for race. Lifestyle
      changes such as diet and physical activity may be universally recommended for all
      persons at risk, regardless of ethnicity and, where necessary, pharmacological
      interventions may be used.

PMID- 15724795
TI  - Hypertensive urgencies and emergencies.
AB  - Severely elevated blood pressure (BP) is commonly encountered in acute care
      settings. Initial evaluation of patients with severe hypertension should focus on
      determining the presence and extent of acute target organ damage. Hypertensive
      emergencies are life-threatening conditions that require immediate reduction of
      BP in an intensive care unit. Hypertensive urgencies-and severe uncontrolled
      hypertension also require prompt attention with gradual lowering of BP. There are
      a number of drugs available for the treatment of these disorders. Careful
      reduction in BP with special attention to cerebral circulation is key to managing
      these patients.

PMID- 15724796
TI  - Education, motivation and medication for African Americans: bringing hypertension
      guidelines to practice.
AB  - African Americans suffer from high rates of hypertension and hypertension-related
      complications. While racial/ethnic differences in blood pressure response to
      pharmacologic therapy have been described, most randomized hypertension trials
      with substantial enrollment of African Americans receiving standardized medical
      care do not support class-specific racial/ethnic differences in key clinical
      outcomes. Understanding health care systems and the socio-economic and
      demographic factors that impair access can enhance the ability of the provider to
      enlist and engage the patient for optimal blood pressure control and end organ
      protection.

PMID- 15724797
TI  - Calcium antagonists: a more expansive role in treating persons with reduced
      kidney function?
AB  - Most recent studies have supported inhibition of the renin-angiotensin
      aldosterone system (RAAS) with diuretic as initial hypertensive therapy in
      patients with chronic kidney disease (CKD). The recommended role of calcium
      channel blockers (CCB) in CKD patients had diminished due to class-specific
      differences in antiproteinuric effects and lesser efficacy in reducing composite
      renal clinical outcomes when compared to RAAS inhibition. However, the
      demonstrated safety and efficacy of CCB in combination with RAAS inhibition, and
      the recognized need for effective antihypertensive agents to achieve the low
      target blood pressures, has prompted a more expanded use of calcium channel
      blockers in this difficult to treat CKD population.

PMID- 15724798
TI  - Bone mineral density changes in young women: a two year study.
AB  - Achievement of a high peak bone mass is considered a pivotal preventive strategy
      against future osteoporotic fractures. The ostensible interaction between
      physiology and lifestylefor the development of bone mass over time is sparsely
      outlined among young women. The aim of this study was to follow bone density and
      bone resorption over time among healthy young women in relation to lifestyle
      factors and to evaluate the perceived influence of other factors. Data were
      collected in 1999 and in 2001. Healthy young women (n=152) were given a
      structured questionnaire, a heel bone scanner (dual X-ray absorptiometry)
      performed bone mineral density measurements and deoxypyridinoline was measured in
      urine. Data were analyzed by linear, multiple and logistic regression analysis.
      Mean bone mineral density (BMD) was 0.562 g/cm2 (+/-0.090). Bone density at
      baseline was the best predictorfor the bone density atfollow-up. Bone density at
      baseline together with smoking and alcohol (dichotomized) accounted for 86.5% of
      the variation in bone density 2 years later. Of the participants 62% had
      decreased/unchanged bone density and 38% had increased their bone density from
      1999 to 2001. Use of oral contraceptives or alcohol at baseline was associated
      with an increased risk of belonging to the group who decreased their bone
      density. Deoxypyridinoline was not a strongpredictor to bone density and all
      potential predictors of deoxypyridinoline had a minor influence (<10%). In
      conclusion, lifestyle behaviors such as use of oral contraceptives, smoking and
      alcohol consumption seem to have a negative influence on BMD development among
      young women and warrant further scrutiny.

PMID- 15724799
TI  - A novel c.C2754 > T transition in the androgen receptor gene introduces the
      premature termination codon Q798X and results in a truncated form of the
      receptor.
AB  - A genetic analysis of a female with a 46,XY genotype and typical symptoms of the
      complete androgen insensitivity syndrome (CAIS) was conducted. The patient was
      diagnosed with an abdominal tumor due to the presence of a Sertoli cell adenoma
      in both gonads. Multiple temperature single-stranded conformational polymorphism
      (MSSCP) and sequence analyses of the androgen receptor gene revealed a c.C2754 >
      T mutation in exon 6. This mutation, which has not been previously reported,
      alters a Gln codon to a termination codon (Q798X). This results in the
      interruption of the amino acid sequence of the androgen receptor within the
      ligand-binding domain between helices VII and VIII. The truncated form of the
      receptor is devoid of 123 amino acids at the carboxyl end, a major part of the
      ligand-binding domain, and the AT2 sequence responsible for the activation of the
      transcription. It was concluded that the novel c.C2754 > T transition rendered
      the androgen receptor incapable of both ligand binding and activating the
      transcription, and was the cause of CAIS in the patient.

PMID- 15724800
TI  - The impact of insulin resistance on the outcome of laparoscopic ovarian
      electrocautery in infertile women with the polycystic ovary syndrome.
AB  - In this study we assessed how insulin resistance affects pregnancy rates in
      infertile women with the polycystic ovary syndrome (PCOS) treated with
      laparoscopic ovarian electrocautery. Sixty-four PCOS women were included in the
      study in a consecutive fashion. Following the CIGMA (continuous infusion of
      glucose with model assessment) test, 28 women were classified as insulin
      resistant and 36 women as non-insulin resistant. After the ovarian electrocautery
      patients were observed for 12-18 months. If pregnancy did not ensue, they were
      referred for one or more cycles of in vitro fertilization (IVF). Following
      ovarian electrocautery the non-insulin-resistant women more frequently achieved a
      regular menstrual cycle and ovulation than the insulin-resistant PCOS women.
      Consequently 18 (50%) of the non-insulin-resistant PCOS women achieved a
      pregnancy versus only five (18%) of women in the insulin-resistant PCOS group.
      Following treatment with both ovarian electrocautery and IVF, 27 (75%) of the non
      insulin resistant PCOS women achieved a successful pregnancy, while 13 (46%) of
      the insulin-resistant PCOS group achieved this. In conclusion, insulin resistance
      may be an important marker of a poor outcome of treatment in PCOS infertility.
      Further studies are needed to evaluate the possible effect of treatment
      alternatives to alleviate the unfavorable influences of insulin resistance and
      hyperinsulinemia on ovulation induction in PCOS women.

PMID- 15724801
TI  - High serum prostate-specific antigen concentrations in hirsute women do not
      decrease with treatment by the combination of spironolactone and the
      contraceptive pill.
AB  - Using an ultrasensitive assay, prostate-specific antigen (PSA) has been detected
      in female serum and has been proposed as a potential marker of androgen excess in
      hirsute women. Measurement of PSA levels in serum may play a role in monitoring
      hirsutism during antiandrogen therapy. We investigated the role of PSA as a
      marker of androgen activity in hirsute patients taking spironolactone together
      with oral contraceptive pills containing ethinyl estradiol and gestodene. Twenty
      eight hirsute patients were included in the study. Clinical and biochemical
      variables including serum levels of PSA (using an ultrasensitive chemiluminscent
      immunoassay), dehydroepiandrosterone sulfate, total testosterone, free
      testosterone and 17-hydroxyprogesterone concentrations were recorded at baseline
      and after six cycles of treatment. Fifteen healthy women were included in the
      study as controls. Serum PSA levels in hirsute women were clearly higher than in
      the control group (0.023 +/- 0.004 vs. 0.006 +/- 0.003 ng/ml, p < 0.001) and
      correlated with baseline serum free testosterone concentrations (r = 0.518, p =
      0.005). After 6 months, serum PSA concentrations as compared with baseline values
      did not change significantly in patients who were given spironolactone plus
      contraceptive pills (p = 0.4) despite a marked decrease in total testosterone,
      free testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and
      hirsutism score (p < 0.05). Thus, serum PSA levels in hirsute women were higher
      than in non-hirsute healthy controls. A 6-month course of treatment with
      spironolactone combined with contraceptive pills containing ethinylestradiol and
      gestodene did not reduce high serum PSA levels in these subjects. In conclusion,
      the serum PSA level is not a convenient biochemical marker with the available
      assays for the management of hirsute women treated with the combination of
      spironolactone and oral contraceptives.

PMID- 15724802
TI  - Treatment effect of sibutramine compared to fluoxetine on leptin levels in
      polycystic ovary disease.
AB  - Weight reduction on its own is observed to cause improvement in some of the
      abnormalities seen in patients with polycystic ovary syndrome (PCOS). With
      respect to this observation, we studied the possible effects of different
      serotonin reuptake inhibitors (fluoxetine and sibutramine) on serum leptin levels
      that might play a role in the obesity component seen in patients with PCOS. In a
      random design, sixteen patients were assigned to fluoxetine and sibutramine for a
      period of 10 days. In both treatment groups, no significant differences were
      observed between pre-treatment and post-treatment values in insulin levels (p >
      0.05). There was no significant difference between pretreatment and post
      treatment serum leptin levels in the fluoxetine treatment group (p > 0.05).
      However, a significant reduction was observed in the serum leptin levels at the
      end of treatment in the sibutramine group (p < 0.05). The observed difference in
      the serum leptin response to the treatment effect of sibutramine compared to
      fluoxetine seems to be due to a mechanism independent of serotonin reuptake
      inhibition, possibly to the thermogenic effect of the sibutramine itself. Further
      studies with larger groups are warranted, to examine the mechanism of the weight
      reducing effect of sibutramine. Detailed analyses of basal metabolic activity and
      change in serum leptin levels should be carried out.

PMID- 15724803
TI  - Efficacy of metformin on ovulation induction in Asian women with polycystic ovary
      syndrome.
AB  - The aim of this study was to assess the efficacy of metformin on induction of
      ovulation in Asian women with clomiphene citrate (CC)-resistant polycystic ovary
      syndrome (PCOS). Twenty PCOS women who did not respond to CC were enrolled in the
      study. All received 500-1500 mg/day of metformin for 4 weeks. If no dominant
      follicle was observed with monitoring by transvaginal ultrasound, 50-150 mg of CC
      per day for 5 days were added. Timing of sexual intercourse was determined or
      intrauterine insemination was carried out 36 h after administration of human
      chorionic gonadotropin. A total of six cycles, pregnancy or anovulation despite
      taking 150 mg of CC were considered as completion of the study. Blood samples
      were obtained before and at the end of the 4th week of treatment for hormonal
      assay. Ovulation was observed in 68 (89.5%) of 76 cycles, of which 34 (44.7%)
      occurred with metformin alone. Twelve women conceived; therefore, the pregnancy
      rate was 17.6% per ovulated cycle and 60% per woman. One (8.3%) had an abortion.
      Four women had minimal adverse effect, but one experienced a severe
      gastrointestinal effect during the fourth cycle. Insulin and androstenedione
      levels were significantly decreased after 4 weeks of treatment. In conclusion,
      these series demonstrated the excellent efficacy of metformin on induction of
      ovulation and pregnancy in Asian women with CC-resistant PCOS.

PMID- 15724804
TI  - Plasma concentration of soluble intercellular adhesion molecule-1 in women with
      polycystic ovary syndrome.
AB  - Soluble intercellular adhesion molecule-1 (sICAM-1) is ranked as one of the
      endothelial dysfunction markers and factors predicting diseases of the
      cardiovascular system. The main objective of this study was to assess the serum
      concentration of sICAM-1 in women with polycystic ovary syndrome (PCOS) and to
      verify correlations between serum sICAM-1 levels and selected anthropometric,
      metabolic and hormonal indices. The study assessed 57 women with PCOS (mean age
      28.2 +/- 6.4 years). That group was further divided into two subgroups: the first
      with body mass index (BMI) < or =25 kg/m2 (21 women of mean age 27.4 +/- 7.0
      years) and the second with BMI >25 kg/m2 (36 women of mean age 28.6 +/- 6.0
      years). In the control group there were 22 healthy women (mean age of 31.6 +/-
      8.5 years). That group again was divided accordingly to BMI into two subgroups:
      the first with BMI <25 kg/m2 (ten women, mean age 30.2 +/- 8.4 years) and the
      second with BMI > 25 kg/m2 (12 women, mean age 31.7 +/- 8.7 years). The results
      demonstrated statistically significantly higher mean concentrations of sICAM-1 in
      women with PCOS as compared to healthy individuals from the whole control group
      and also from the control subgroup of women with BMI >25 kg/m2. There was no
      statistically significant difference in sICAM-1 concentration between the PCOS
      group and the control subgroup with BMI < or =25 kg/m2 In conclusion, higher
      concentrations of sICAM-1 in women with PCOS may confirm the presence of a higher
      risk for cardiovascular diseases in this group. Further studies are therefore
      necessary to identify both the factors that are responsible for the increase in
      sICAM-1 concentration and the clinical usefulness of routine sICAM-1 measurement
      in females with PCOS.

PMID- 15724805
TI  - Sex-steroid hormones, gonadotropin and ovarian carcinogenesis: a review of
      epidemiological and experimental data.

PMID- 15724806
TI  - Sexual differentiation of the human brain: relevance for gender identity,
      transsexualism and sexual orientation.
AB  - Male sexual differentiation of the brain and behavior are thought, on the basis
      of experiments in rodents, to be caused by androgens, following conversion to
      estrogens. However, observations in human subjects with genetic and other
      disorders show that direct effects of testosterone on the developing fetal brain
      are of major importance for the development of male gender identity and male
      heterosexual orientation. Solid evidence for the importance of postnatal social
      factors is lacking. In the human brain, structural diferences have been described
      that seem to be related to gender identity and sexual orientation.

PMID- 15724807
TI  - The diagnosis of premenstrual syndromes and premenstrual dysphoric disorder-
      clinical procedures and research perspectives.
AB  - Premenstrual syndromes (PMS) are quite prevalent among women of reproductive age.
      In up to 20% of women they are severe enough to warrant treatment, which is
      available and marketed as such. The impact of the cumulative burden of PMS is
      substantial and is in the same magnitude as affective disorders. Nevertheless,
      the definitions and diagnoses of PMS are still fragmented, not widely accepted
      and, if accepted, not always applied in day-to-day clinical practice. In the
      present paper, the current diagnostic entities are critically reviewed, problems
      with the current definitions are delineated and a unified definition is proposed.
      For clinical purposes, the recommended dinical practical diagnostic process and
      differential diagnosis are described. For clinical trials of medications for
      treatment of PMS/premenstrual dysphoric disorder, research diagnostic criteria,
      inclusion and exclusion criteria, as well as well-defined outcome measures, are
      of utmost importance; they are described here. The gaps of knowledge in the
      description and diagnosis of PMS are described, with suggestions for future
      directions for research.

PMID- 15724808
TI  - Gonadotropin-releasing hormone-stimulated gonadotropin levels in women with
      premenstrual dysphoria.
AB  - Despite consistent evidence that premenstrual dysphoria (PMD) is not
      characterized by abnormalities in basal ovarian hormone secretion, the
      possibility remains that PMD is associated with an abnormality in the regulation
      of the hypothalamic-pituitary-ovarian (HPO) axis. We studied HPO axis regulation
      in 11 women with prospectively confirmed PMD and 20 asymptomatic controls, during
      both the follicular and luteal phases of the menstrual cycle. Plasma levels of
      the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH), were obtained before and after stimulation with gonadotropin-releasing
      hormone (GnRH) (100 microg intravenously). Potential diagnostic- and menstrual
      cycle phase-related diferences in basal and plasma hormone levels were analyzed
      by repeated-measures analysis of variance. No significant differences were
      observed between women with PMD and controls in either basal or stimulated levels
      of FSH and LH. Stimulated FSH was significantly increased and stimulated LH was
      significantly decreased during the follicular compared with the luteal phase in
      both women with PMD and controls. These data are consistent with prior findings
      of normal basal reproductive hormone levels in women with PMD. Our data suggest
      the absence in women with PMD of an abnormality of dynamic ovarian function as
      measured by GnRH stimulation.

PMID- 15724809
TI  - Disadaptive disorders in women: allopregnanolone, a sensitive steroid.
AB  - Allopregnanolone, a neurosteroid acting as a potent anxiolytic agonist of the
      gamma-aminobutyric acid A receptor, has been shown in animal models to modify its
      concentrations at central and peripheral levels according to the estrous cycle.
      Moreover, it modulates behavioral and biochemical responses to acute and chronic
      stress, anxiety, depression, aggressiveness, convulsions, anesthesia, sleep,
      memory, pain and feeding. These observations suggest that fluctuations of
      allopregnanolone might be involved in the development, course and prognosis of
      some mental disorders in humans. This has been hypothesized for depressive
      disorders, premenstrual dysphoria, anorexia and bulimia nervosa and Alzheimer's
      disease, where increased, decreased or dysregulated secretion of the main
      neurosteroids and their metabolites has been observed. Women show a marked gender
      related sensitivity to disadaptive disorders. In addition to the well-studied
      role of sex steroids in modulating mood and behavior, a putative involvement of
      neurosteroid fluctuations, and in particular of allopregnanolone, has recently
      been hypothesized. In fact, several paraphysiological events and various
      disadaptive disorders in women are associated with modifications of circulating
      levels of this neurosteroid that might associated with a certain vulnerability to
      an altered adaptation to stressful life events.

PMID- 15724810
TI  - Hormone therapy and risk for dementia: where do we go from here?
AB  - Prospective observational studies suggest that hormone therapy (HT) might confer
      protection against the development of Alzheimer's disease. In contrast, recent
      findings from the Women's Health Initiative Memory Study (WHIMS) indicated a
      doubling of the risk of all-cause dementia in women randomized to receive HT
      after age 64. The discrepancy between findings from observational studies and the
      WHIMS is commonly attributed to the lack of treatment bias in the randomized
      trial. However, there are other potentially important dfferences between the
      WHIMS and the observational studies. These include timing of initiation of HT and
      type of HT regimen used. The present review focuses on the clinical and basic
      science studies bearing on these clinically important issues. Additional clinical
      studies are needed to understand the external generalizability of the WHIMS
      results to populations of women for whom HT remains an indication.

PMID- 15724811
TI  - Europe's innovation barriers.

PMID- 15724812
TI  - Parasites, flies and men--21st Meeting of the German Society of Parasitology in
      Wurzburg.
AB  - The German Society of Parasitology (Deutsche Gesellschaft fur Parasitologie) was
      founded in 1960 and its 21st biannual meeting took place in Wurzburg, Germany,
      from March 17 to 20, 2004. Whereas interim meetings that are being held every
      other year focus on specific topics of parasitology, such as the symposia on
      "Life in Vacuoles" in 2003 and on "Immunomodulation by Parasites" in 2001, the
      general biannual meetings cover a wide range of topics. This year's meeting at
      the University of Wurzburg was organised by Klaus Brehm and Matthias Frosch (both
      at the Institute of Hygiene) and Heidrun Moll (Institute for Molecular Biology of
      Infectious Diseases). It was attended by more than 500 scientists from 16
      countries who presented 181 research projects dealing with the topics defence
      mechanisms and immunology, genomics and proteomics, epidemiology, cell biology
      and biochemistry, chemotherapy and vaccines, parasite classification and
      morphology, vectors, intermediate hosts, and veterinary parasitology. In
      addition, six plenary lectures highlighted the subjects of comparative nematode
      genomics, cell biology, immunology, and parasite eradication programmes.

PMID- 15724813
TI  - The role of ICAM-1 in Plasmodium falciparum cytoadherence.
AB  - Parasite sequestration at microvascular sites is a fundamental phenomenon in the
      manifestation of the symptoms of malaria and the progression to severe disease.
      Here, we review the endothelial cell-expressed intercellular adhesion molecule-1
      (ICAM-1) and its role in mediating the interaction between the parasitised red
      blood cell (PRBC) and the vascular endothelium. We highlight the nature of the
      interaction between ICAM-1 and the parasite-expressed PfEMP-1 molecule at the
      molecular level. The review also discusses the complexity of the PRBC-endothelial
      cell interaction and the mechanisms that underlie parasite cytoadherence.

PMID- 15724814
TI  - Impairment of anterograde and retrograde neurofilament transport after anti
      kinesin and anti-dynein antibody microinjection in chicken dorsal root ganglia.
AB  - The purpose of the present study was to investigate the participation of the
      motor proteins kinesin and dynein in axonal transport of neurofilaments (NF) in
      cultured dorsal root ganglia neurons. Therefore, we performed live-recording
      studies of the green fluorescent protein-tagged neurofilament M (GFP-NF-M) to
      assay transport processes in neurons. Co-localization studies revealed that GFP
      NF-M was capable to build a functional NF network with other NF subunits,
      including phosphorylated heavy neurofilaments (NF-H-PH). Time-lapse recordings
      using confocal laser scanning microscopy exhibited fast transport of NF dots in
      anterograde and retrograde direction through a photobleached gap. Following
      microinjection of anti-kinesin antibodies or colchicine treatment an impairment
      of anterograde as well as retrograde NF transport was observed during live
      recording experiments. In contrast, microinjection of anti-dynein antibodies only
      impaired retrograde transport of NF whereas the anterograde movement of GFP-NF-M
      was unaffected. Treatment of the cells with unspecific antibodies had no effect.

PMID- 15724815
TI  - Stepwise mechanical stretching inhibits chondrogenesis through cell-matrix
      adhesion mediated by integrins in embryonic rat limb-bud mesenchymal cells.
AB  - Biomechanical forces are major epigenetic factors that determine the form and
      differentiation of skeletal tissues, and may be transduced through cell adhesion
      to the intracellular biochemical signaling pathway. To test the hypothesis that
      stepwise stretching is translated to molecular signals during early
      chondrogenesis, we developed a culture system to study the proliferation and
      differentiation of chondrocytes. Rat embryonic day-12 limb buds were
      microdissected and dissociated into cells, which were then micromass cultured on
      a silicone membrane and maintained for up to 7 days. Stepwise-increased
      stretching was applied to the silicone membrane, which exerted shearing stress on
      the cultures on day 4 after the initiation of chondrogenesis. Under stretched
      conditions, type II collagen expression was significantly inhibited by 44% on day
      1 and by 67% on day 2, and this difference in type II collagen reached 80% after
      3 days of culture. Accumulation of type II collagen protein and the size of the
      chondrogenic nodules had decreased by 50% on day 3. On the other hand, expression
      of the non-chondrogenic marker fibronectin was significantly upregulated by 1.8
      fold on day 3, while the up-regulation of type I collagen was minimal, even by
      day 3. The downregulation in the expression of chondrogenic markers was
      completely recovered when cell-extracellular matrix attachment was inhibited by
      Gly-Arg-Gly-Asp-Ser-Pro-Lys peptide or by the application of blocking antibodies
      for alpha2, alpha5 or beta1 integrins. We conclude that shearing stress generated
      by stepwise stretching inhibits chondrogenesis through integrins, and propose
      that signal transduction from biomechanical stimuli may be mediated by cell
      extracellular matrix adhesion.

PMID- 15724816
TI  - HAb18G/CD147 enhances the secretion of matrix metalloproteinases (MMP) via
      cGMP/NO-sensitive capacitative calcium entry (CCE) and accordingly attenuates
      adhesion ability of fibroblasts.
AB  - The present study examined the effect of hepatoma-associated antigen HAb18G
      (homologous to CD147) expression on the NO/cGMP-regulated Ca2+ mobilization to
      induce matrix metalloproteinases (MMP) production and attenuate adhesion ability
      of mouse fibroblast NIH/3T3 cells. HAb18G/CD147 cDNA was transfected into
      fibroblast 3T3 cells to obtain a cell line stably expressing HAb18G/CD147, t3T3,
      as demonstrated by immunofluorescence staining and flow cytometry assays. 8-Bromo
      cGMP inhibited the thapsigargin-induced Ca2+ entry in 3T3 cells, whereas an
      inhibitor of protein kinase G, KT5823 (1 microM), led to an increase in Ca2+
      entry. Expression of HAb18G/CD147 in t3T3 cells decreased the inhibitory response
      to cGMP. A similar effect on the Ca2+ entry was observed in 3T3 cells in response
      to an NO donor, (+/-)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory
      effect of SNAP on the thapsigargin-induced Ca2+ entry was also reduced in
      HAb18G/CD147-expressing t3T3 cells, indicating a role for HAb18G/CD 147 in
      NO/cGMP-regulated Ca2+ entry. Results of gelatin zymography assays showed that
      addition of extracellular Ca2+ induced MMP (MMP-2, MMP-9) release and activation
      in a dose-dependent manner, and expression of HAb18G/CD147 enhanced the secretion
      of MMP-2 and MMP-9 in 3T3 cells. 8-Bromo-cGMP and SNAP reduced the production of
      MMP in 3T3 cells but not in t3T3 with HAb18G/CD147 expression. RT-PCR experiments
      substantiated that the expression of MMP-2 and MMP-9 mRNA in HAb18G/CD 147
      expressing t3T3 cell was significantly greater than that in 3T3 cells.
      Experiments investigating adhesion potentials demonstrated that HAb18G/CD147
      expressing t3T3 cells pretreated with Ca2+ attached to Matrigel-coated culture
      plates significantly less efficiently than 3T3 cells. The proportion of attached
      cells could be increased by treatment with 8-bromo-cGMP and SNAP in 3T3 cells,
      but not in t3T3. These results suggest that HAb18G/CD147 attenuates adhesion
      potentials in fibroblasts by enhancing the secretion of MMP through NO/cGMP
      sensitive capacitative Ca2+ entry.

PMID- 15724817
TI  - Knockdown of the centrosomal component SAS-5 results in defects in nuclear
      morphology in Caenorhabditis elegans.
AB  - Several different processes must be completed in order to proceed through cell
      division. First, the centrosomes have to be duplicated and the genomic material
      is replicated. The separation of the chromatin is achieved by a bipolar spindle,
      which in turn is organized by the two centrosomes. The last step of cell division
      involves the separation of cellular content and the cleavage of the cell by
      cytokinesis. We used RNAi to study the centrosomal component SAS-5 in the early
      Caenorhabditis elegans embryo. While the first cell division and the
      establishment of polarity of sas-5 dsRNA-treated embryos was indistinguishable
      from wild type, subsequent cleavages were abnormal. Time-lapse microscopy studies
      of worms expressing beta-tubulin::GFP revealed that the absence of SAS-5 results
      in a failure of mitotic spindle assembly starting at the two-cell stage embryo.
      Furthermore, the chromatin in at least one of the two cells in the early embryo
      was dispersed. Yet, this dispersion did neither trigger apoptosis nor affect
      nuclear envelope assembly. No intrinsic size control for the nucleus seems to
      exist in the early embryo.

PMID- 15724818
TI  - Opioid analgesics for cancer pain in primary care.
AB  - Each year, around 140,000 people die from cancer in England and Wales, about one
      quarter of them in the community. Two crucial goals in the palliative care of
      such people are to enhance quality of life and control symptoms. Of particular
      importance, morethan two-thirds of patients with cancer will require opioid
      analgesics to control pain. Since many patients with cancer, including those with
      advanced disease, aim to spend more time at home rather than in hospital, the
      primary care team has an important role in managing pain. The team, supported by
      community clinical nurse specialists and specialist palliative care units, is
      often responsible for initiating analgesic therapy and for ongoing assessment of
      patients' pain and analgesic requirements. Here we discuss key issues in using
      opioids for cancer-related pain in primary care.

PMID- 15724819
TI  - Antiepileptics, pregnancy and the child.
AB  - Around 3-6 in every 1,000 pregnant women have epilepsy, and many of them are
      taking antiepileptic therapy. Such treatment, and the epilepsy itself, are
      associated with important adverse outcomes in the child. Here we review the
      evidence on such problems and update our previous advice on the use of
      antiepileptic treatment in women who are pregnant or planning to conceive.

PMID- 15724820
TI  - Community mental health nursing and early intervention in dementia: developing
      practice through a single case history.
AB  - People Nursing in association with Journal of Clinical Nursing 13, 6b, 57-67
      Community mental health nursing and early intervention in dementia: developing
      practice through a single case history This paper reports on a single case
      history taken from the 'Dementia Action Research and Education' project, a 15
      month primary care intervention study that was undertaken in North Wales in the
      early part of 2000. The study sought to address the meaning, context and
      diversity of early intervention in dementia care and employed a community mental
      health nurse and a psychiatric social worker to undertake early and psychosocial
      interventions with older people with dementia (aged 75 years and over) and their
      families. The workers tape-recorded, documented and analysed their interventions
      with 27 older people with dementia and their families over the 15-month duration
      of the study. Clinical supervision was also undertaken during the intervention
      phase. One case history is presented in this paper to illustrate the work of the
      community mental health nurse and to identify areas of practice development.
      Greater role transparency, collaborative working and improvement in educational
      preparation for practice are called for.

PMID- 15724821
TI  - Implication of Internet growth on enhancing health of disadvantaged groups in
      China: a global perspective.
AB  - The Internet is promising to play a prominent role in health care in the future,
      but there is an imbalance in its use between the East and the West, between
      genders, the rich and poor, the educated and uneducated and the urban and rural.
      This paper looks at the use of the Internet from the perspective of these
      subgroups across the world, and outlines some of the problems facing
      disadvantaged groups in particular older people and their caregivers in China.
      Older people and their predominantly family caregivers have limited access to
      computers which is compounded by lack of access to good health care. However, it
      is suggested that this will become a growth area as older people and their
      caregivers may well bypass traditional care for telehealth care and Internet
      information-based systems.

PMID- 15724822
TI  - A literature review exploring how healthcare professionals contribute to the
      assessment and control of postoperative pain in older people.
AB  - Little research has examined the care older people receive in the acute surgical
      setting. Although pain assessment and management are judged to be a priority in
      nursing, often pain, in older people, is undermanaged for a variety of reasons.
      Factors such as stoicism, communication and ageism can shape both the patients'
      and nurses' attitude towards the perception of pain which subsequently affects
      pain management. Through a review of the literature, this paper aims to: (i)
      identify how healthcare professionals contribute to the assessment and control of
      postoperative pain in older people and (ii) explore potential barriers to
      achieving more advantageous pain control in this group. It is suggested that to
      improve pain management there is a need to individualize pain assessment for
      older people and to assist clinicians with enhancing their education and decision
      making abilities in this field. This may best be achieved by supporting a
      programme of change to develop the skills of staff and encouraging learning
      through reflective practice. There is however a need for further research in this
      area.

PMID- 15724823
TI  - The effect of music listening on acute confusion and delirium in elders
      undergoing elective hip and knee surgery.
AB  - This study was undertaken to determine the effect of music on elders undergoing
      elective hip and knee surgery who experience acute confusion and delirium
      postoperatively. Postoperative confusion and delirium in elders often cause
      complications that negatively effect recovery. Music listening was introduced as
      an intervention to an experimental group. Nurses documented episodes of acute
      confusion and delirium experienced by elders postsurgically. Scores from a
      readiness-to-ambulate profile to determine if patients were cognitively ready for
      postoperative therapy were evaluated. There was a significant decrease in the
      number of episodes of postoperative confusion among those in the experimental
      group compared with those in the non-listening control group. In addition, the
      experimental group had significantly higher scores on the readiness-to-ambulate
      profile than the control group. These findings indicate that music listening is
      an effective nursing intervention that can be used to decrease acute
      postoperative confusion and delirium in elders undergoing elective hip and knee
      surgery.

PMID- 15724824
TI  - Older people's views on rural life: a study of three villages.
AB  - In the context of increasing interest in how rurality affects health services and
      nursing practice in the UK, this paper reports and discusses data from a survey
      of older people living in three English villages. The survey found that village
      populations differed widely, that there were changes in the proportions of older
      people in the villages over time, and that close social networks existed for some
      but not all. The paper concludes that health care practitioners should avoid
      stereotypes of village life. In their increasing emphasis on health promotion and
      active ageing among older people, nurses may find data collected by the voluntary
      sector to be a useful resource. Working in partnership with groups to achieve a
      deep understanding of local contexts may assist nursing practitioners when
      building up pictures of older patients' health-related needs and views.

PMID- 15724826
TI  - Preventive home care of frail older people: a review of recent case management
      studies.
AB  - Preventive actions targeting community-dwelling frail older people will be
      increasingly important with the growing number of very old and thereby also frail
      older people. This study aimed to explore and summarize the empirical literature
      on recent studies of case/care management interventions for community-dwelling
      frail older people and especially with regard to the content of the interventions
      and the nurse's role and outcome of it. Very few of the interventions took either
      a preventive or a rehabilitative approach using psycho-educative interventions
      focusing, for instance, on self-care activities, risk prevention, health
      complaints management or how to preserve or strengthen social activities,
      community involvement and functional ability. Moreover, it was striking that very
      few included a family-oriented approach also including support and education for
      informal caregivers. Thus it seems that the content of case/care management needs
      to be expanded and more influenced by a salutogenic health care perspective.
      Targeting frail older people seemed to benefit from a standardized two-stage
      strategy for inclusion and for planning the interventions. A comprehensive
      geriatric assessment seemed useful as a base. Nurses, preferably trained in
      gerontological practice, have a key role in case/care management for frail older
      people. This approach calls for developing the content of case/care management so
      that it involves a more salutogenic, rehabilitative and family-oriented approach.
      To this end it may be useful for nurses to strengthen their psychosocial skills
      or develop close collaboration with social workers. The outcome measures examined
      in this study represented one of three perspectives: the consumer's perspective,
      the perspective of health care consumption or the recipient's health and
      functional ability. Perhaps effects would be expected in all three areas and thus
      these should be included in evaluative studies in addition to measures for family
      and/or informal caregiver's strain and satisfaction.

PMID- 15724825
TI  - The Quality of Life in Alzheimer's Disease Scale: direct assessment of people
      with cognitive impairment.
AB  - BACKGROUND: A need exists, consistent with a person-centred approach to dementia
      care, to facilitate collaborative approaches to the assessment of quality of
      life. AIMS AND OBJECTIVES: To examine the concept of quality of life, to make the
      case for its centrality in dementia care provision and to consider the validity
      and reliability of one tool (Quality of Life in Alzheimer's Disease Scale, QOL
      AD). CONCLUSIONS: The use of the QOL-AD aligns with person-centred principles
      incorporating the subjective viewpoint of the person with dementia, thereby
      promoting a collaborative and inclusive approach to the measurement of the
      concept of quality of life. RELEVANCE TO CLINICAL PRACTICE: Utilization of QOL-AD
      in clinical practice facilitates a user-centred and collaborative approach to the
      assessment of quality of life. This approach is in keeping with contemporaneous
      forces in health and social care delivery for people with dementia.

PMID- 15724827
TI  - Processes, outcomes and evaluation: challenges to practice development in
      gerontological nursing.
AB  - When aligned to participants' needs, evaluation may be used to enhance practice
      developers' work. Process evaluation enables practice developers to evaluate as
      they develop; making evaluation an integral part of practice development rather
      than an 'add on task'. It is contended that beginning practice developers can
      discharge their need to evaluate their work through the practice development
      techniques of critical reflection, dialogue and action learning. These form the
      basis of iterative and formative evaluation activity. However other types of
      evaluation are important for different audiences in practice development.
      Consideration of the purpose and utility of evaluation in a range of contexts in
      which gerontological nursing occurs, brings some clarity regarding the scope of
      the evaluation required to sustain practice development initiatives. In addition,
      it helps to clarify the nature of the evaluation required to provide evidence of
      patient-centred outcomes from developments in the practice of gerontological
      nursing.

PMID- 15724828
TI  - Exploring the future of gerontological nursing outcomes.
AB  - This paper explores some of the global challenges in gerontological nursing and
      suggests that nurses need to be able to identify better more appropriate person
      centred outcomes, to justify their own worth in caring for older people. It
      highlights some of the methodological difficulties of measuring outcomes for
      older people and, more generally, of determining the value and contribution of
      nursing. It argues that, to address some of these methodological challenges, more
      participative approaches to research are needed, highlighting the particular
      value of action research. It suggests that if research is to be meaningful to
      both older people and those caring for them, there is an urgent need for
      gerontological nursing research to become much more person-centred and
      practice/action oriented.

PMID- 15724829
TI  - Loneliness and depression in independent living retirement communities: risk and
      resilience factors.
AB  - Socio-emotional selectivity theory posits that as individuals age, they desire
      less social stimulation and novelty, and tend to select close, reliable
      relationships to meet their emotional needs. Residence in congregate facilities
      affords social exposure, yet does not guarantee access to close relationships, so
      that loneliness may be a result. Further, the gerontology literature has
      suggested that loneliness in late life may be a risk factor for serious mental
      health concerns such as depression. This article examined data on loneliness and
      depressive symptoms from older adults aged 60-98, residing in two age-segregated
      independent living facilities. Overlap between those scoring in the depressed
      range on the Geriatric Depression Scale and those scoring more than one standard
      deviation above the mean on the UCLA Loneliness Scale was less than 50%, although
      zero-order correlation of the two continuous scores was moderately high.
      Potential risk and resilience factors were regressed on the continuous scores of
      the two scales in separate hierarchical multiple regression analyses. Depression
      was predicted by being older, number of chronic health conditions, grieving a
      recent loss, fewer neighbor visitors, less participation in organized social
      activities and less church attendance. Grieving a recent loss, receiving fewer
      visits from friends, and having a less extensive social network predicted
      loneliness. In addition, loneliness scores explained about 8% of the unique
      variance in depression scores, suggesting it is an independent risk factor for
      depressive symptoms. Loneliness scores were seen to be more widely dispersed in
      these respondents, with less variance explained by the available predictors.
      Suggestions are made for addressing loneliness in older adults as a means of
      preventing more serious mental health consequences.

PMID- 15724830
TI  - A model predicting suicidal ideation and hopelessness in depressed older adults:
      the impact of emotion inhibition and affect intensity.
AB  - The purpose of this study was to begin a preliminary examination of constructs
      theorized to be related to suicidal behavior by testing a model of the influence
      of both temperament and emotion regulation on suicidal ideation and hopelessness
      in a sample of depressed older adults. The model was evaluated using structural
      equation modeling procedures in a sample of depressed, older adults. Findings
      supported a temporally predictive model in which negative affect intensity and
      reactivity lead to emotion inhibition, operationalized as ambivalence over
      emotional expression and thought suppression, which in turn lead to increased
      presence of suicidal predictors, operationalized as hopelessness and suicidal
      ideation. These results suggest that suicide prevention efforts in older adults
      may be improved by targeting emotion inhibition in treatment, especially among
      affectively intense and reactive older adults.

PMID- 15724831
TI  - Examining physician-patient-caregiver encounters: the case of Alzheimer's disease
      patients and family physicians in Israel.
AB  - This study examines the characteristics of physician-patient-caregiver encounters
      in the presence of dementia and how sociodemographic and professional
      characteristics of family physicians, and severity of symptoms in patients with
      dementia affect these encounters. Phone interviews were conducted with 141
      Israeli-Jewish family physicians (representing a 66% response rate), who were
      presented with one of two vignettes describing a 76-year old women with dementia.
      The two vignettes were identical, except that in the first it was stated that the
      woman sits quietly and cooperates during the examination whereas in the second
      she is agitated and uncooperative. Participants were asked to what extent they
      would ask questions to, inform and involve the patient and caregiver respectively
      when presented with one of the two vignettes. Findings showed that physicians
      would address the caregiver more than the patient (both with respect to
      questions, information and involvement). Moreover, it was found that physicians,
      who were older and had a higher number of years in the profession, would address
      the caregiver to a higher degree (compared to the patient) than younger and less
      experienced physicians. Findings provide direction for understanding medical
      encounters in the presence of dementia. Theoretical implications for dementia
      care, for medical encounters, and practical implications are discussed.

PMID- 15724832
TI  - Psychological predictors of admission and discharge global assessment of
      functioning scale scores for geropsychiatric inpatients.
AB  - This study examined psychological predictors of Global Assessment of Functioning
      Scale scores (GAF) at intake and at discharge for geropsychiatric inpatients. A
      total of 301 predominantly male geropsychiatric inpatients were recruited from
      the Houston Veterans Affairs Medical Center. Path analysis was used to test a
      model proposing causal paths of psychological predictors (cognitive status,
      depression, agitation, general psychiatric status) to GAF scores on admission and
      discharge. At admission, all four psychological predictors had positive paths to
      the admission GAF scale scores but at discharge, only two (i.e., cognitive status
      and general psychiatric status) of the four psychological predictors had positive
      paths to the discharge GAF scale scores. The admission GAF scale scores also had
      a positive path to the discharge GAF scale scores. The overall functioning level
      of geropsychiatric inpatients may be predicted by measures which assess overall
      cognitive status and general psychiatric functioning during hospitalization.
      Results prompt consideration of a modified global scale specifically reflecting
      an older adult's activities during this period of life.

PMID- 15724833
TI  - Influence of cognitive impairment, functional impairment and care setting on
      dementia care mapping results.
AB  - Quality of life (QOL) for people with dementia has become a major focus over the
      past decade. Dementia care mapping (DCM) is an observational measure of quality
      of care given by staff in formal care settings, as well as a measure of QOL that
      has been used in many studies of people with dementia in residential care
      settings. However, the method itself has not been rigorously studied in a
      scientific manner. For this report, mapping data were collected for 166 persons
      with dementia in three types of care settings: special care facilities that are
      licensed nursing homes, assisted living facilities, and adult day centers. The
      relationships between DCM and several independent variables including cognitive
      status, functional status, care setting, depression, length of stay, and co
      morbid illnesses were assessed. Both cognitive status and functional status were
      found to be associated with DCM scores. Moreover, DCM was sensitive in
      differentiating among persons with four levels of cognitive impairment.
      Implications for practice are discussed.

PMID- 15724834
TI  - Hip fracture-related changes in health ratings of older patients with cognitive
      impairment.
AB  - A hip fracture is traumatic for many older adults, often leading to declines in
      both health and health perception. Although health ratings often decrease from
      pre- to post-fracture, nothing is known about what influences cognitively
      impaired patients to assess their post-fracture health as they do. We developed a
      causal model of health perception following a hip fracture and previously
      reported this causal model for older hip fracture patients of high mental status.
      This study evaluates the same causal model on 145 patients of low mental status.
      We found a substantial reorganization of relative health and functional ratings,
      indicative of the highly disruptive impact of the hip fracture. Our findings
      suggest physical rehabilitation may aid in recovery from hip fracture and this
      merits further study.

PMID- 15724835
TI  - Preferences of older African-Americans for long-term tube feeding at the end of
      life.
AB  - The purpose of this study was to elicit preferences and reasons behind
      preferences for percutaneous endoscopic gastrostomy (PEG) tube placement in an
      older African-American sample. Five focus groups were conducted with subjects
      invited from the Geriatric Clinic of an urban tertiary care hospital. Thematic
      and latent content analyses were used. Five broad themes emerged as reasons
      behind the acceptance or rejection of a PEG tube, namely: the nature of the
      illness; the quality of life at the time of the decision; the concern about
      dependency; experiences; and religion (including issues of death). The issue of
      proxy also arose and contained three themes: fear of loss of decision-making
      ability; trust in family or caregivers as proxy even when the proxy choices
      differed from their own choices; and trust in the doctor and family to respect
      personal decisions. Use of a qualitative approach enabled potentially sensitive
      issues to be discussed. Preferences and the reasons behind these preferences may
      not always be anticipated by clinicians.

PMID- 15724836
TI  - Ethnic differences in social network help-seeking strategies among Latino and
      Euro-Aamerican dementia caregivers.
AB  - This research explores the help-seeking behavior of Euro-American and Latino
      caregivers who provide homecare assistance to an older adult with dementia. A
      community sample of 89 caregiver-care recipient pairs (39 Latino and 50 Euro
      American) was interviewed. Descriptive, bivariate, and multivariate analyses were
      conducted to examine ethnic differences in use of an informal social network for
      help with caregiving tasks. Caregiver experiences that may impact help-seeking
      behaviors such as perceived availability of support network, satisfaction with
      support received and caregiver distress were also considered. Latino caregivers
      reported less help-seeking than did the Euro-American caregivers. Overall,
      ethnicity accounted for 16% of the variation in help-seeking behaviors. Ethnicity
      accounted for a significant portion of the variation in most of the help-seeking
      characteristics examined even after adjusting for socioeconomic variables. In the
      multivariate model, the effects of ethnicity on help-seeking persisted, while the
      effects of other likely predictors did not. The size of social network may not be
      synonymous with the seeking of support by caregivers. Likewise, higher levels of
      distress among Latino caregivers did not result in increased help-seeking
      behaviors. There remains a need to identity what other factors may contribute to
      the cultural variability in caregivers' use of informal support.

PMID- 15724837
TI  - Therapeutic effects of Lycium barbarum polysaccharide (LBP) on mitomycin C (MMC)
      induced myelosuppressive mice.
AB  - AIM: To investigate the therapeutic effects of Lycium barbarum polysaccharide
      (LBP) on mitomycin C (MMC)-induced myelosuppressive mice. METHODS: Mice were
      intravenously injected with MMC 150 mg/kg for two consecutive days from day -1 to
      day 0 to produce severe myelosuppression, and then treated by s.c. injections of
      LBP (100 or 200 mg/kg/day) from days 0 to 6. Blood samples were collected from
      the tail veins of mice on days 7, 10, 12, 14, 17, 19, 21, 24 and 27, and
      peripheral white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB) and
      platelet counts (PLT) etc. were monitored. RESULTS: LBP at 100 mg/kg (LBP-L) on
      day 14 and LBP at 200 mg/kg (LBP-H) on days 10, 14, 17, 19 and 21, significantly
      ameliorated the decrease of peripheral RBC, HGB and hematocrit (HCT) of
      myelosuppressive mice compared to the control. LBP-L on days 12 and days 14 and
      LBP-H on days 10, 12, 14, 17, 19 and 21, significantly enhanced peripheral PLT
      recovery of myelosuppressive mice compared to the control. LBP-H on days 12, 17,
      19 and 21, significantly inhibited the increase of mean platelet volume (MPV) of
      myelosuppressive mice compared to the control. LBP showed no obviously effect on
      neutropenia induced in mice by MMC. CONCLUSION: LBP is effective on peripheral
      RBC and PLT recovery of MMC-induced myelosuppressive mice.

PMID- 15724838
TI  - Determination of cysteine peptidases-like activity and their inhibitors in the
      serum of patients with ovarian cancer treated by conventional chemotherapy and
      vitamin E.
AB  - Enzymatic activity of cysteine peptidases (cathepsins B and L) --associated with
      carcinogenesis is controlled by their specific inhibitors. The study was objected
      to the effects enhanced by taxol and cisplatin in patients pretreated with the
      vitamin E, by determining the levels of cathepsins B and L in sera of patients
      with ovarian cancer. The activity of cysteine peptidase (CP) and their inhibitors
      (CPI) in serum from patients with ovarian cancer and noncancerous patients were
      measured by using fluorogenic substrate before and after the routine anticancer
      chemotherapy, and a complementary combination of chemotherapy with vitamin E. The
      cat B and L activities were significantly higher in patient sera with ovarian
      cancer than non-cancerous patients (0.0001 pounds sterling). The results shows
      that, inhibitory activity of CPI and complex form were significantly decreased
      from 4.6 mEU/mg protein in a group of non-cancerous patients to 0.7 mEU/mg
      protein in a group of patients with ovarian cancer (p < or = 0.0001).
      Supplementation with vitamin E after a cycle of therapy with toxic drugs caused a
      decrease of the cysteine peptidases activities, that is 2.8-fold in patients to
      whom 40 0mg of vitamin E per day was given in comparison with control, and 6-fold
      after the third course. The CPI and DCPI complex increased 3-fold and 2.3 fold
      respectively, as compared to a group of patients were vitamin E was not
      administered. We observed that vitamin E administered to the patients with
      ovarian cancer in periods between anticancer drugs therapy courses decreases the
      cysteine peptidases activity and increases the enzyme-inhibitor complexes level

PMID- 15724839
TI  - Molecular impacts of antisense complementary to the liver fatty acid binding
      protein (FABP) mRNA in DU 145 prostate cancer cells in vitro.
AB  - Previous studies in our laboratory have showed that liver (L)-FABP and intestine
      FABP were upregulated in prostate cancer cells whereas Adipose-FABP and epidermal
      FABP were down regulated in cancer cells when compared to normal cells in tissue
      cultures and biopsy samples (Das et al, 2001). We have also shown that blocking
      the expression of L-FABP resulted in remarkable effects on apoptosis and cell
      proliferation of prostate cancer cell lines. Another study showed that induction
      of A-FABP inhibited proliferation DU 145 prostate cancer cells (DeSantis et. al.,
      Journal of Experimental Therapeutics and Oncology, 4:91-100, 2004) and caused a
      downregulation of the L-FABP transcript levels. This suggests that there is a
      correlation in the expression between of A-FABP and L-FABP in prostate cancer
      cells and that high expression of A-FABP is associated with a downregulation of L
      FABP and vice versa. This study examines the mechanism by which L-FABP antisense
      regulates proliferation and apoptosis in prostate cancer cell lines. We used
      human cDNA array blots and custom DNA microarrays to explore differentially
      expressed genes in DU 145 prostate cancer cells treated with L-FABP antisense
      oligonucleotide. Genes that were differentially expressed were confirmed using
      quantitative RT-PCR. Genes correlating with proliferation were downregulated and
      antiproliferative genes were upregulated in response to antisense to L-FABP. This
      suggests a possible use of these antisense ODNs as therapeutic agents for
      prostate cancer in future.

PMID- 15724840
TI  - Protective effect of a polyherbal preparation, Brahma rasayana against tumor
      growth and lung metastasis in rat prostate model system.
AB  - Rasayanas are a group of herbal formulations and are used to improve health of
      the body. Recent studies have demonstrated the immunostimulatory and antioxidant
      activities of some of these rasayanas and their usefulness in tumor regression.
      The objective of the study is to evaluate Brahma rasayana for the inhibition of
      tumor development and prevention of metastasis in vivo using Copenhagen rats and
      MAT-LyLu cell model system. Copenhagen rats injected with MAT-LyLu cells were
      treated with Brahma rasayana once daily. This treatment was followed from the
      second day of cell inoculation until the end of the experiment. The study
      comprises a comparison of survival time, body weight, tumor incidence, tumor
      size, tumor weight, histopathological examination of the lung metastasis and
      serum testosterone levels between rasayana treated and control animals. Brahma
      rasayana treatment resulted in a 25-37% decrease in palpable tumor incidence, a
      delay of 1-2 weeks in the tumor occurrence, lower mean tumor volumes, by as much
      as 14-35% and significant reduction in tumor weight and lung metastasis in
      comparison to untreated controls. The Ayurvedic poly herbal preparation, Brahma
      rasayana may play a beneficial role in preventing tumor incidence, tumor growth
      and metastatic spread. These are inexpensive preparations that have little or no
      adverse side effects with a potential as lead chemopreventive compounds and which
      might prove useful for the treatment of disorders such as human prostate cancer.

PMID- 15724841
TI  - Implications of p53 in growth arrest and apoptosis on combined treatment of human
      Mammary epithelial cells with topotecan and UCN-01.
AB  - We previously reported (Cancer Chemother Pharmacol 45: 252-258, 2000) that UCN-01
      (7-hydroxystaurosporine), a protein kinase inhibitor, which is under clinical
      trials as an anti-cancer agent in the USA and Japan, enhanced camptothecin
      induced cytotoxicity in breast cancer cells that lack p53 function. This
      enhancement was mediated by the abrogation of G2 arrest of tumor cells.
      Subsequent studies from our laboratory also revealed that the combined use of
      both UCN-01 and camptothecin induced DNA double strand breaks in p53 mutant tumor
      cells but not in normal or p53 negative epithelial cells. In this study, we
      report the implication of p53 on growth arrest and apoptosis following the
      combined treatment of human mammary epithelial cells with topotecan, a specific
      topoisomerase I inhibitor, and UCN-01. Experiments were performed on the
      following cells: normal human mammary epithelial cells (HMEC) with wild type p53,
      HME cells transfected with HPV16 E6 protein which inactivates p53 (HMEC/E6), and
      MDA231 mammary tumor cells with p53 mutation. UCN-01 selectively enhanced the
      cytotoxicity of topotecan in both MDA231 and HMEC/E6 cells. In contrast, UCN-01
      showed little pharmacological effect, if any, on HME cells. Median-effect
      analysis indicated that a synergistic cytotoxic interaction existed between UCN
      01 and topotecan in both MDA231 and HMEC/E6 cells, whereas, in the normal HME
      cells, the growth inhibition was only additive. Detailed cell-cycle analyses
      revealed that UCN-01 abrogated S-phase accumulation induced by topotecan
      treatment in p53 defective MDA231 tumor cells and HMEC/E6 cells. No changes in
      the cell cycle profiles of the normal HME cells were observed. In combination,
      UCN-01 and topotecan induced maximum apoptotic response on both HMEC/E6 and
      MDA231 cells at 6 and 48 hrs, respectively. These data indicate that UCN-01
      selectively enhances topotecan cytotoxicity in p53 defective cells through the
      induction of apoptotic signaling pathway(s), although the time course for the
      induction of cell death is not the same. UCN-01 may, therefore, provide a new
      modality for topotecan-based therapy, particularly in p53 defective cancer
      patients.

PMID- 15724842
TI  - 3-amino thioacridone inhibits DNA synthesis and induce DNA damage in T-cell acute
      lymphoblastic leukemia (T-ALL) in a p16-dependent manner.
AB  - In T-cell Acute Lymphocytic Leukemia (T-ALL), the inhibitors of cyclin-dependent
      kinases (CDK) 4 and 6, p16 and p15, are inactivated almost universally at the
      DNA, RNA and protein levels. This suggests that CDK-targeting may be an effective
      therapeutic approach for T-ALL and other cancers. In this study, we tested 3
      inhibitors of CDK4, 3-aminothioacridone (3-ATA), thioacridone (TA), and oxindole,
      for their effects on DNA synthesis and viability in primary T-ALL. Each compound
      was an effective inhibitor, with overall IC(50)s in similar ranges. In colony
      formation assay, leukemic cells were approximately 10-fold more sensitive to 3
      ATA than normal bone marrow cells. When sorted by G1 protein status of T-ALL,
      p16(+), p15(+) or pRb(-) samples were significantly less sensitive to 3-ATA and
      TA, but not to oxindole, than p16(-), p15(-) or pRb(+) samples. There was no
      relationship of sensitivity with ARF expression. Despite their in vitro function
      as inhibitors of CDK4, 3-ATA did not inhibit pRb phosphorylation or cause G1
      arrest, but did cause DNA damage and result in the induction and phosphorylation
      of p53. We conclude that 3-ATA efficacy can be predicted by p16 status in T-ALL,
      but the mechanism of action may be distinct from their in vitro ability to
      regulate CDK4 kinase activity

PMID- 15724844
TI  - The monitoring of the accumulation of protoporphyrin IX in Walker tumours by
      subcutaneous administration of delta-aminolevulinic acid.
AB  - Photodynamic therapy with protoporphyrin IX induced by delta-aminolevulinic acid
      (ALA) is mainly applied for the treatment of human superficial skin cancer. In
      this paper we present our study on photodynamic therapy (PDT) of the implanted
      Walker tumours using subcutaneous administration of ALA to improve the
      availability of ALA in the skin. We determined the accumulation and localization
      of protoporphyrin IX (PpIX) after subcutaneous administration of different
      concentrations of ALA in a physiological saline solutions, using fluorescence
      imaging technique. The results obtained indicate that PpIX accumulation depends
      on the concentration of ALA. The temporal behavior of PpIX fluorescence has shown
      a clear demarcation of tumoural zone depending on the post-administration time
      and the administrated concentration of the ALA solution. Further studies are
      needed to confirm these encouraging results and to define the PDT protocols using
      subcutaneous administration of ALA solution

PMID- 15724843
TI  - Human ATP-binding cassette transporter ABCC10: expression profile and p53
      dependent upregulation.
AB  - Human ATP-binding cassette (ABC) transporter genes are classified into seven sub
      families, where "C" subfamily comprises a total of 13 gene members. The ABCC10
      cDNA was cloned in the human full-length cDNA project at the Kazusa DNA Research
      Institute. However, current information is limited regarding its physiological
      function and gene expression. In the present study, we have investigated the
      expression of the ABCC10 gene to gain insight into its biological nature. By
      quantitative PCR, ABCC10 gene expression is demonstrated to be highest in
      pancreas among the adult and fetal tissues and tumors presently tested. Decreased
      expression was observed when resting T- and B-cells were activated. Furthermore,
      when we examined its expression under apoptotic conditions, we found that ABCC10
      mRNA levels remarkably increased in doxorubicin-treated MCF7 cells, whereas its
      up-regulation was suppressed in p53-dominant-negative MCF7 cells. These results
      suggest that expression of the ABCC10 gene is regulated in a p53-dependent manner
      during DNA-damage-related apoptosis.

PMID- 15724845
TI  - The 24th International Symposium of Sapporo Cancer Seminar "Pharmacogenomics in
      Cancer Chemotherapy: Recent Advances in ABC Transporters and Genome Analyses".
      Hokkaido University Conference Hall, Sapporo, Japan, June 20-22, 2004.

PMID- 15724846
TI  - Evaluation of protective ointments used against dermal effects of nitrogen
      mustard, a vesicant warfare agent.
AB  - Mustard, a vesicant warfare agent, has cytotoxic, mutagenic, and cytostatic
      effects via alkylation of DNA and inhibition of DNA replication. Since symptoms
      appear following a latent period, it can cause some subacute and chronic effects
      to occur and delay in the treatment. Therefore, the main approach should be the
      use of protective preparation to reduce the skin toxicity. Thus, this study was
      conducted in guinea pigs (350-400 g) shaved in areas of 10 x 10 cm.
      Mechlorethamine HCl (100 mg), a nitrogen mustard derivative, in ethanol was
      applied by spraying on hairless regions where previously prepared pharmaceutical
      topical formulations were medicated before. The experimental regions of the
      animals were kept preserved from environmental factors. Forty-eight hours after
      the application of the protective ointments and mechlorethamine consecutively,
      skin-damaging effects were macroscopically evaluated in terms of erythema
      formation, ulceration, necrosis, and inflammation occurrences. Then, punch biopsy
      was performed from these damaged sites for histopathological evaluation. Although
      numerous topical formulations were prepared and tested for protection, according
      to microscopic examination of the pathologic sections, tissue specimen treated
      with the ointment containing the mixture of zinc oxide, zinc chloride,
      dimethylpolysiloxane in a base of petroleum jelly was determined as being the
      most effective protective against skin injury caused by the vesicant agent.

PMID- 15724847
TI  - Prehospital physiologic data and lifesaving interventions in trauma patients.
AB  - BACKGROUND: The ability to accurately triage trauma patients can be difficult in
      the prehospital environment. Prehospital trauma scoring systems have been
      developed with a goal of determining which patients should be transported
      immediately to a trauma center, thus benefiting from critical personnel and
      resource-intensive lifesaving interventions (LSIs). A resource-based endpoint,
      LSIs, therefore might be the optimal endpoint of prehospital triage scoring and
      could be used to determine where patients are transported. We hypothesized that
      simple physiologic data available immediately upon scene arrival would prove
      predictive of the need for a LSI. METHODS: Trauma patients transported from the
      injury scene by helicopter were eligible for entry into the study. Prehospital
      physiologic data and interventions were timed and recorded by flight medical
      personnel, whereas hospital vital signs, injuries, and interventions were
      prospectively recorded from the inpatient records. The motor component of the
      Glasgow Coma Scale was used as an indicator of neurologic function. LSIs were
      procedures deemed lifesaving by a multidisciplinary panel of trauma experts.
      RESULTS: Physiologic data were collected from August 2001 to February 2002. Data
      were collected for 216 random patients transported by the Life Flight helicopter
      service. There were no differences between LSI and non-LSI patients in age,
      gender, or transport time, and 80 patients underwent 197 LSIs. The mean age was
      33 +/- 17 years, 73% of patients were male, 90% suffered blunt injury, the injury
      severity score was 14 +/- 9, hypotension (systolic blood pressure of < 90 mm Hg)
      was present in 14% of cases, and the mortality rate was 6%. Penetrating injury
      and increasing injury severity score were associated with LSI. Univariate
      analysis of the physiologic data immediately available in the field revealed that
      SBP of < 90 mm Hg, motor score of < 6, delayed capillary refill, and increasing
      pulse were significantly associated with a LSI. However, multivariate analysis
      revealed that only SBP of < 90 mm Hg and motor score of < 6 were associated with
      a LSI. When both variables were abnormal, 95% of patients required a LSI; when
      both variables were normal, 21% of patients required a LSI. CONCLUSIONS: The
      presence of hypotension or decreased motor score was correlated with the need for
      LSIs. However, normotensive patients with normal motor scores still frequently
      required LSIs. Optimal discrimination of this group of patients will require new
      analytic approaches.

PMID- 15724848
TI  - Analysis of health factors as predictors for the functioning of military
      personnel: study of the factors that predict fitness for duty and medical costs
      of soldiers of the Royal Netherlands Army.
AB  - In 1998, the Royal Netherlands Army introduced a new examination system, which is
      based on the "workload-capability" model, to replace the old system, which
      focused on diagnosis and was solely based on the detection of diseases and
      infirmities. In a randomized controlled study, we found that soldiers recruited
      under the new system displayed a statistically significant higher number of days
      fit-for-duty and incurred lower medical costs than solders recruited under the
      old system. To gain a better understanding of the reasons for these differences,
      we studied the association between these results and information collected about
      the soldiers. In the course of the study, we collected various types of
      information about the study participants (e.g., education, deployment). During
      the study, soldiers were asked to complete a questionnaire twice a year, its
      content based in part on a periodic occupational health examination questionnaire
      commonly used in The Netherlands. We found that the following factors influenced
      fitness for duty and medical consumption: education, injuries, actual operational
      deployment, and the examination system itself. The superior performance of the
      new RNLA Basic Medical Requirements (BMEKL) system seems partly attributable to
      the assessment of the ability to meet the task-specific requirements. The primary
      mechanism is as yet undiscovered.

PMID- 15724849
TI  - Army junior dental officer retention.
AB  - OBJECTIVES: The objectives of the survey were to quantify the extent of
      indebtedness of junior dental officers and to determine the impact of a loan
      repayment program on career decisions. METHODS: We designed a customized survey
      instrument because no preexisting, validated, survey instrument was available. A
      query was performed in the Medical Operations Data System to identify all
      captains (0-3) currently on active duty in the Army (N = 348). The survey sample
      included 64 junior officers with a 2000 date of rank to captain (0-3), of whom
      only 52 were in the Medical Command Outlook address book or the Army Knowledge
      Online white pages. The questionnaire was sent out to these targeted junior
      dental officers through their official e-mail accounts. Dentists assigned to
      Korea and to dental field units do not use the same e-mail system as the rest of
      the Dental Command; therefore, their addresses were not available. In an attempt
      to increase response rates, commanders were asked to emphasize the importance of
      responding to the questionnaire. RESULTS: From the sample population of 52
      officers who were queried directly, 34 responses were received, for a response
      rate of 65%. However, commanders forwarded the survey to all Dental Command
      captains and 102 responses were received. The respondents represented 30% of the
      total Army inventory of captains; 92% of respondents reported that they had
      dental school loans, with 43% reporting loans in excess of dollar 50,000. The
      average dental school indebtedness was approximately dollar 60,700. More than 60%
      of all respondents reported that loan repayment could change their minds about
      remaining on active duty. Officers not included in the original sample rated the
      impact of loan repayment statistically higher than did officers in the original
      sample. CONCLUSIONS: The findings were that the majority of junior Army dental
      officers had significant student loans and many of these officers indicated that
      they would consider remaining on active duty if loan repayment or other monetary
      inducements were offered.

PMID- 15724850
TI  - Is a Dental Health Risk Assessment predictive of dental health?
AB  - A complete dental examination is the basis for identifying the dental readiness
      of Air Force Reserve Command members. Historically, these were done on an
      infrequent basis. Recently, an annual dental examination has been mandated for
      all military members. Current dental personnel manning and resources are not
      sufficient to accomplish this dramatic increase in dental examination workload.
      To help alleviate this demand, a Dental Health Risk Assessment questionnaire was
      developed and tested to see if it could accurately screen out a dental problem
      severe enough to make a member non-worldwide deployable (Dental Readiness
      Classification of 3). These members would be scheduled for a dental examination
      first. The questionnaire asked members to self-identify dental health problems.
      Their answers were compared with the findings from the military dental
      examination. Unfortunately, the results did not match the survey's expectation.
      Accurately predicting who needed to be scheduled for a comprehensive dental
      examination, based on how a member answered the survey questions, was not
      accomplished. It is hoped that further research and refinement may make a
      predictive Dental Health Risk Assessment possible.

PMID- 15724851
TI  - The most frequently requested precombat refresher training by the Special Forces
      medics during Operation Enduring Freedom.
AB  - The tactical environment and the mission given the Special Operations Forces in
      Afghanistan during the initial phases of Operation Enduring Freedom placed the
      Special Operations Forces medics (18Ds) in a position of significant medical
      responsibility. The 18Ds became the primary care providers for the indigenous
      anti-Taliban fighters as well as U.S. military personnel; the care of the latter
      was further complicated by long evacuation times. Because of these issues and
      several events that occurred in the combat zone, the 18Ds requested their
      supporting forward surgical team (FST) (274th FST) to provide specific refresher
      training before combat deployment into Afghanistan. The areas of greatest
      interest and concern were orthopedics, field transfusions, and field-expedient
      anesthesia. It is hoped that the training prepared and given to the 18Ds by the
      personnel of the 274th FST and presented in this article not only was useful to
      them but also will be of benefit to 18Ds who find themselves in similar
      situations in the future.

PMID- 15724852
TI  - Unplanned pregnancy among active duty servicewomen, U.S. Air Force, 2001.
AB  - Unplanned pregnancy is a major public health problem in the United States.
      Although the U.S. Air Force has the highest proportion of active duty women of
      any of the U.S. military services, there are no published data on the occurrence
      of unplanned pregnancy among active duty Air Force (ADAF) women. Civilian female
      interviewers conducted telephone interviews with a random sample of 2,348 ADAF
      women during early 2002, using questions that were closely based on the 1995
      National Survey of Family Growth. During 2001, approximately 12% of ADAF women
      had one or more pregnancies. By National Survey of Family Growth criteria,
      approximately 54% of these pregnancies were unplanned. Thus, approximately 7% of
      ADAF women had one or more unplanned pregnancies during 2001. Roughly one-half of
      unplanned pregnancies represented contraceptive nonuse and the other half
      represented contraceptive failure or misuse. Unplanned pregnancy is a serious and
      frequently occurring problem among ADAF women, with many opportunities for
      prevention.

PMID- 15724853
TI  - Psychiatric symptoms and cognitive appraisal following the near sinking of a
      research submarine.
AB  - OBJECTIVE: This study assessed the stress reactions of a submarine crew forced to
      abandon their vessel in high seas after flooding and fire damaged their ship.
      METHODS: The remaining crew members (n = 22) were surveyed 7 months after the
      incident regarding exposures, initial emotional responses, peritraumatic
      dissociation, subsequent life events, current safety appraisal, and current
      symptoms of posttraumatic stress disorder (PTSD) and depression. RESULTS: At 7
      months, 9.1% met criteria for PTSD and none met criteria for depression. Higher
      levels of depressive symptoms were associated with previous traumatic exposures,
      subsequent life events, and higher levels of PTSD symptoms; higher levels of PTSD
      symptoms were associated with greater peritraumatic dissociation and initial
      emotional response. CONCLUSION: Acute exposures of highly trained professionals
      to potentially fatal events may not result in high levels of posttraumatic
      symptoms. Previous and subsequent life events may play a more significant role in
      the level of postdisaster symptoms.

PMID- 15724854
TI  - Morbidity and mortality characteristics of infants hospitalized in the Pediatrics
      Department of the largest Turkish military hospital in 2001.
AB  - A descriptive study was conducted in the pediatric inpatient unit of Gulhane
      Military Medical Academy, to investigate the morbidity and mortality
      characteristics of 532 infants hospitalized between January 1 and December 31,
      2001, for treatment purposes. Of the study participants, 55.8% were boys and
      44.2% were girls. The most common cause of hospitalization was neonatal
      hyperbilirubinemia (19.7%). The most common admission month was January (12.4%).
      Of 532 infants, 510 (95.9%) were discharged, whereas 22 patients died in the
      hospital. Twenty-one patients died in the neonatal period, and respiratory
      distress syndrome and neonatal sepsis were identified as the most common causes
      of death. Our finding of associations between male gender and low birth weight
      and hospital death is consistent with previous knowledge. Despite the high
      frequencies of pneumonia and gastroenteritis as admission diagnoses, the finding
      of only one pneumonia-related death and no gastroenteritis-related deaths in the
      study population is pleasing.

PMID- 15724855
TI  - N-acetyl-L-Cysteine as prophylaxis against sulfur mustard.
AB  - Sulfur mustard (HD) is a blister agent targeting the eyes, respiratory system,
      skin, and possibly other organs. Extensive exposure can destroy the immune system
      by destruction of bone marrow cells. There is no antidote for HD or effective
      treatment other than rapid decontamination. Clinical trials have demonstrated
      activity for N-acetyl-L-cysteine (NAC) against a number of significant human
      pathologies involving free radicals, and animal and tissue studies have suggested
      efficacy for NAC as a chemoprotectant against many toxic chemicals. Among these
      are studies demonstrating that NAC significantly reduces the effects of HD and HD
      simulants, both in cultured cells and animals. Given the historical effectiveness
      of HD, the lack of any effective treatment, the demonstrated chemoprotective
      properties of NAC, its low toxicity, the lack of regulatory controls, and the
      data supporting efficacy against HD effects, we suggest daily oral administration
      of the maximum safe dose of NAC to personnel entering combat zones.

PMID- 15724856
TI  - The role of radiology in dive-related disorders.
AB  - Recreational scuba diving has continued to grow in popularity in the past several
      decades, and military diving remains an integral part of ship husbandry,
      explosives and ordinance disposal, and special warfare. Although relatively
      uncommon, disorders such as decompression sickness and arterial gas embolism can
      be fatal, whereas disorders such as ear baro-trauma and dysbaric osteonecrosis
      are not fatal but can cause significant morbidity. An extensive literature search
      was performed to comprehensively examine the current role of diagnostic radiology
      with respect to diving medicine. In selected cases, diagnostic imaging can be of
      potential benefit for evaluation. Diagnostic imaging plays a useful role in the
      screening of certain individuals for future fitness to dive. Radiological imaging
      has also been of paramount importance in postmortem evaluation of dive
      casualties.

PMID- 15724857
TI  - Hemorrhage control in the battlefield: role of new hemostatic agents.
AB  - Uncontrolled hemorrhage is the leading cause of preventable combat-related
      deaths. The vast majority of these deaths occur in the field before the injured
      can be transported to a treatment facility. Early control of hemorrhage remains
      the most effective strategy for treating combat casualties. A number of
      hemostatic agents have recently been deployed to the warfront that can be used to
      arrest bleeding before surgical control of the source. The purpose of this
      article is to summarize the background information regarding these hemostatic
      agents, indications and rationale for their use, and characteristics of these
      products that may impact effectiveness.

PMID- 15724858
TI  - Predicting costs of Veterans Affairs health care in Gulf War veterans with
      medically unexplained physical symptoms.
AB  - Measures of post-traumatic stress disorder (PTSD) and depression were used to
      predict Veterans Affairs outpatient treatment costs among Persian Gulf War
      veterans with medically unexplained physical symptoms. Patients (N = 206)
      enrolled in a Veterans Affairs primary care clinic for Persian Gulf War veterans
      completed study assessments at the initial appointment or at a proximal follow-up
      visit. Costs of care for mental health, medical, and pharmacy services for these
      veterans were computed for the subsequent 6-month period. Depression and PTSD
      symptoms explained a significant share of variance in costs of mental health care
      and pharmacy services, after adjustment for covariates. None of the mental status
      measures was significantly related to costs of medical care. Models using global
      measures of mental health status were as robust as models using disorder-specific
      measures of PTSD and depression in predicting mental health care and pharmacy
      costs. The implications of these findings for anticipating costs of care for
      Persian Gulf War veterans are discussed.

PMID- 15724859
TI  - Evaluation of commercially available fluid-warming devices for use in forward
      surgical and combat areas.
AB  - The fluid-warming capabilities of four individual fluid warmers, i.e., Level 1,
      FMS 2000, Thermal Angel, and Ranger, were compared to evaluate their potential
      for medical use in forward military echelons of care. Lactated Ringer's solution
      (LR) and Hextend at room temperature (20 degrees C) or refrigerated temperature
      (4-7 degrees C) and packed red blood cells at 4 degrees C to 7 degrees C were
      used with each warmer at two different flow rates. The FMS 2000 consistently
      warmed all fluids to approximately 37 degrees C, regardless of the starting
      temperature or flow rate. The Level 1 and Ranger also efficiently warmed all
      fluids except cold LR to approximately 37 degrees C. The Thermal Angel generally
      warmed room temperature fluid, cold Hextend, and packed red blood cells to at
      least 33 degrees C to 34 degrees C but could not warm cold LR. The clinical
      standard is to have fluids warmed to 32 degrees C at a minimum and more
      preferably to 34 degrees C to 35 degrees C. Of the fluid warmers tested, only the
      Thermal Angel failed to achieve such a temperature in warming cold LR. Data from
      the present study suggest the Ranger and FMS 2000 to be operationally adaptable
      to at least echelons 1 and 2, respectively, whereas far-forward use of the
      Thermal Angel has limitations.

PMID- 15724860
TI  - Do iodine water purification tablets provide an effective barrier against
      Cryptosporidium parvum?
AB  - U.S. Army Iodine Water Purification Tablets were tested to determine their
      efficacy against Cryptosporidium parvum, a protozoan resistant to chemical
      disinfection. Purified oocysts in phosphate-buffered water were treated with
      varying concentrations of iodine or with iodine tablets as per U.S. Army
      protocol. Neonatal mouse pups were then each inoculated with 10,000 treated
      oocysts, and 1 week later scored as infected or uninfected. Using this
      methodology, iodine tablets were found to be inadequate against C. parvum because
      the Army doctrinal dose of 560 mg min/L, calculated as 16 mg of I2/L and 35
      minutes of contact time, showed less than 1 log inactivation. A dose of 29 mg of
      I2/L at the same contact time was required to achieve a 2 log inactivation.

PMID- 15724861
TI  - Predictors of psychiatric hospitalization in the Navy.
AB  - Mental disorders represent an important source of morbidity among U.S. military
      personnel and are a common reason for early separation from the military. The
      objective of this study was to identify factors predictive of hospitalization for
      mental health disorders in a large sample of enlisted Navy personnel. Demographic
      variables and a variety of psychosocial variables assessed on the Sailors' Health
      Inventory Program questionnaire were studied as predictors of psychiatric
      hospitalization. Three psychiatric categories were examined: adjustment reaction,
      personality disorder, and all other mental health disorders. Several variables
      were significantly predictive of all three categories of psychiatric
      hospitalization: female gender, low education level, history of abuse (physical,
      emotional, or sexual), and tobacco smoking. The results of this study support
      efforts to develop better psychological screening methods and potential
      interventions aimed at helping recruits adapt to military life.

PMID- 15724862
TI  - Clinical presentations for influenza and influenza-like illness in young,
      immunized soldiers.
AB  - Concern about respiratory diseases in soldiers increased in the late 1990s as
      production of the successful adenovirus vaccines stopped and the possibilities of
      an emergent pandemic influenza strain and use of bioweapons by terrorists were
      seriously considered. Current information on the causes and severity of influenza
      like illness (ILI) was lacking. Viral agents and clinical presentations were
      described in a population of soldiers highly immunized for influenza. Using
      standard virus isolation techniques, 10 agents were identified in 164 (48.2%) of
      340 soldiers hospitalized for ILI. Influenza isolates (29) and adenoviruses (98)
      occurred most frequently. Most influenza cases were caused by influenza A and
      probably resulted from a mismatch between circulating and vaccine viruses. Most
      (58.5%) patients with an adenovirus had a chest radiograph; 31.3% of these had an
      infiltrate. Clinical findings did not differentiate ILI caused by the various
      agents. Only 29 cases of influenza occurred in approximately 7,200 person-years
      of observation, supporting the use of influenza vaccine.

PMID- 15724863
TI  - Magnesium research: from the beginnings to today.
AB  - The beginnings of magnesium research, from the 18th century to the first quarter
      of the twentieth century, consists mainly of the development of chemical and
      pharmacological knowledge. The modern period began in 1926 when the essential
      character of magnesium was acknowledged. The early part of the modern period, up
      to the 1960s, saw the foundation of our knowledge of the basic physiological,
      epidemiological and clinical aspects. The present modern period began in 1971
      with the First International Symposium on Magnesium and the subsequent creation
      of SDRM (the international Society for the Development of Research on Magnesium),
      an international coordinating structure, which promotes the publication of
      magnesium books (volumes of proceedings and monographs) and of journals:
      Magnesium Research the international official organ of SDRM and several national
      journals: the Journal of Japanese Society for Magnesium Research (Japan), the
      Buletin informativ al societatii romane de cercetare a magneziului (Romania), the
      Journal of Elementology (Poland) and which regularly organizes national and
      international meetings. The next great international meeting will be held on
      October 23-26, 2006 in Osaka (Japan). We will discuss the latest research
      findings on magnesium in health and disease. The subject shows that today
      magnesium research remains active in basic sciences and embraces all the facets
      of pathology.

PMID- 15724864
TI  - Effects of magnesium sulfate on Na+,K+ -ATPase and intracranial pressure level
      after cerebral ischemia.
AB  - In the present study, the effects of magnesium sulfate on Na+,K+ -ATPase levels
      and intracranial pressure (ICP) after cerebral ischemia in rabbits were studied.
      Thirty New Zealand rabbits were divided into three groups. Group 1 was the
      control group. In group 2 (untreated group) cerebral ischemia was produced by
      clamping bilateral common carotid arteries for 60 min but in group 3 magnesium
      sulfate was administered 100 mg/kg i.v. 10 min after opening the clamps. In group
      1, ICP recordings were obtained 5, 60 and 120 min after craniectomy. In groups 2
      and 3, ICP recordings were obtained 5 min after craniectomy but before clamping,
      60 min after clamping and 60 min after opening the clamps. After taking ICP
      recordings, brain cortices were resected and Na+,K+ -ATPase activity was
      determined by subtracting the enzyme activity in the presence of ouabain from the
      total activity in the absence of ouabain method. There was a significant
      difference between Na+,K+ -ATPase levels of group 1 and group 2 (P < 0.05). There
      was no significant difference in Na+,K+ -ATPase levels between group 1 and 3 (P >
      0.05), also preischemic ICP values were same in all groups (P > 0.05).
      Preischemic and postischemic ICP values were significantly different between
      groups 1 and 2 (P < 0.05), also postischemic (120 min) ICP values were
      significantly different between group 2 and group 3 (P < 0.05). ICP values
      correlate well with Na+,K+ -ATPase level. These results demonstrate that cerebral
      ischemia leads to a decrease of ATPase level in the brain and magnesium sulfate
      suppresses the decrease of Na+,K+ -ATPase, also magnesium sulfate treatment
      improves the ICP changes.

PMID- 15724865
TI  - Magnesium influence on nicotine pharmacodependence and smoking.
AB  - We followed the magnesium effect (Magne B(6)R, Sanofi-Synthelabo) with internal
      administration in 53 adult neurotic smoking patients (more than 10
      cigarettes/day) of both genders admitted into psychiatric hospital. The nicotine
      dependence was assessed by the Fagerstrom test, initially and after 28 days of
      magnesium intake. Plasmatic magnesium level was determined before any therapy and
      at 28 days. All patients received benzodiazepines during the trial. Our data show
      that patients that received magnesium therapy showed a significant decrease in
      the number of cigarettes smoked and Fagerstrom test after 4 weeks [Fagerstrom
      score 7.93 +/- 0.17 before magnesium therapy versus 6.78 +/- 0.18 (P < 0.05)
      after 28 days of magnesium therapy]. In the group of smokers who did not receive
      magnesium, the Fagerstrom score did not change significantly [Fagerstrom score
      7.48 +/- 0.22 initial versus 7.24 +/- 0.19 after 28 days]. Magnesium
      supplementation raised plasmatic levels (17.2 +/- 1.2 mg/L before versus 26.1 +/-
      1.6 mg/L after 28 days of magnesium intake, P < 0.01). The results suggest that
      this cation might be a useful adjuvant in treatment of nicotine
      pharmacodependence.

PMID- 15724866
TI  - The influence of magnesium supplementation on concentrations of chosen
      bioelements and toxic metals in adult human hair. Magnesium and chosen
      bioelements in hair.
AB  - The basic functions of bioelements in biological systems is widely known.
      Depletion of bioelements and excess of toxic elements lead to impairment of
      metabolism in the living organism. The existence of magnesium deficiencies in the
      adult and pediatric populations may cause increased accumulation of toxic metals
      including lead and cadmium. Prevention of adverse effects of toxic metals may
      include supplementation with some bioelements and vitamins. The aim of this study
      was to evaluate the influence of magnesium supplementation on concentrations of
      chosen bioelements and toxic metals in hair in the adult human population. The
      research was performed on 124 individuals (53 males and 71 females aged 19-72
      years), inhabitants of the city of Szczecin. The concentrations of magnesium,
      zinc, copper, lead and cadmium were studied in hair. Measurements were performed
      using the inversion volt-amperometry method with application of an EDD-Tribo PC
      ETP volt-amperometer. Finally, the supplementation study enrolled 65 individuals
      with an increased concentration of lead. The studied individuals were divided
      into two groups: one treated group that enrolled 50 patients who were
      supplemented with magnesium and the control group that enrolled 15 persons
      receiving placebo. Finally, supplementation was completed by 32 individuals from
      the treated group and 10 individuals from the control group. Supplementation was
      performed using Slow-Mag-B6 preparation at the total daily dose of five tablets
      divided into 2-3 doses. One tablet contains 535 mg of magnesium chloride i.e. 64
      mg of magnesium ions (5.26 mEgMg2) and 5 mg of vitamin B6. Supplementation was
      performed for a period of 3 months. The remaining individuals did not complete
      the supplementation due to various reasons; however, none of them resulted from
      the poor tolerance of the preparation or its adverse events. The results achieved
      underwent statistical analysis. The results of the study revealed a positive
      influence of supplementation on concentrations of magnesium and copper in the
      human body. Supplementation with magnesium caused a statistically significant
      decrease in concentrations of lead and cadmium. The above mentioned results
      indicate a positive influence of magnesium supplementation on the decrease of
      lead and cadmium hair content in the individuals studied.

PMID- 15724867
TI  - Elevated concentrations of TNF-alpha are related to low serum magnesium levels in
      obese subjects.
AB  - The aim of this study was to determine the relationship between serum magnesium
      and TNF-alpha levels in obese subjects. A cross-sectional population based study
      that included 192 non-diabetic, non-hypertensive subjects allocated in three
      categories of body mass index (BMI) <25; > or =25 to <30 kg/m2; and > or =30
      kg/m2. Elevation of TNF-alpha levels was defined by serum levels > or =3.5 pg/mL,
      and low serum magnesium by levels < or = 0.74 mmol/L. Multivariate odds ratios
      (OR) adjusted by age, HOMA-IR index, and glucose tolerance status are presented.
      Obese subjects exhibited higher serum concentration of TNF-alpha (p = 0.002) and
      lower serum magnesium levels (p < 0.0001) than lean and overweight subjects.
      Ninety-one (47.4%) subjects showed elevated levels of TNF-alpha, of them 7
      (10.9%), 31 (48.4%), and 43 (67.2%) in the groups with BMI <25, > or = 25 to < 0,
      and >> or =0 kg/m2, respectively. Multivariate OR between low serum magnesium and
      TNF-alpha levels in obese subjects was of 1.8, Cl95% 1.2-9.1, P = 0.001, whereas
      in the lean and overweight individuals of 1.1, Cl95% 0.7-8.7, P = 0.12, and 1.3,
      Cl95% 0.9-10.8, P = 0.09, respectively. These data shows that low serum magnesium
      levels and elevated TNF-alpha are related in the obese subjects. It will be
      necessary to conduct more studies in order to add new data on this issue.

PMID- 15724868
TI  - The alteration of magnesium, calcium and phosphorus metabolism by dietary
      magnesium deprivation in postmenopausal women is not affected by dietary boron
      deprivation.
AB  - A study with human volunteers was conducted to test the hypothesis that naturally
      occurring inadequate intakes of magnesium induce negative magnesium balance and
      undesirable changes in calcium metabolism variables, and that these changes are
      influenced by dietary boron. Diets composed of ordinary Western foods providing
      approximately 118 and 318 mg Mg/d and approximately 0.25 and 3.25 mg B/d were fed
      in a double-blind Latin square design to 13 healthy, post menopausal Caucasian
      women (aged 50-78 years) living in a metabolic unit. Magnesium balance, which was
      positive when dietary magnesium was 318 mg/d, became negative when dietary
      magnesium was 118 mg/d. Magnesium deprivation decreased urinary calcium
      excretion, and significantly increased calcium balance when balance data analyzed
      came from all collections during the 42-day periods. Urinary phosphorus excretion
      was increased, but fecal phosphorus excretion was decreased, thus phosphorus
      balance was not significantly affected by magnesium deprivation. Magnesium
      deprivation did not affect manganese or zinc balance. The balance data indicated
      that 700 mg of calcium, 1.0 mg of manganese, and 10 mg of zinc were adequate for
      post menopausal women. Magnesium deprivation increased serum 25
      hydroxycholecalciferol and decreased serum total cholesterol concentrations.
      Boron deprivation increased but magnesium deprivation decreased urinary potassium
      excretion. Boron supplementation decreased serum 17beta-estradiol and
      progesterone when dietary magnesium was low. The dietary treatments did not
      affect serum calcitonin, parathyroid hormone, osteocalcin or alkaline phosphatase
      concentrations. One woman placed on consecutive magnesium-low dietary periods
      exhibited heart ventricular ectopy after consuming the magnesium-low diet for 72
      days; the ectopy disappeared upon consuming the magnesium-adequate diet. The
      findings indicated that consuming an ordinary diet deficient in magnesium,
      resulting in negative magnesium balance, can affect calcium, potassium, and
      cholesterol metabolism. Dietary boron did not have an obvious effect on the
      response to magnesium deprivation.

PMID- 15724869
TI  - Birth cohort studies in psychiatry: beginning at the beginning.

PMID- 15724870
TI  - The Nottingham Study of Neurotic Disorder: predictors of 12-year outcome of
      dysthymic, panic and generalized anxiety disorder.
AB  - BACKGROUND: Controlled prospective studies of the simultaneous long-term outcome
      of several mental disorders are rare. This study sought to determine if there
      were important differences between the outcome of anxiety and depressive
      disorders after 12 years and to examine their main predictors. METHOD: A cohort
      of 210 people seen in general practice psychiatric clinics with a DSM-III
      diagnosis of generalized anxiety disorder (71), panic disorder (74), or dysthymic
      disorder (65), including combined anxiety-depressive disorder (cothymia) (67) was
      followed up after 12 years. Interview assessments of symptoms, social functioning
      and outcome were made, the latter using a new scale, the Neurotic Disorder
      Outcome Scale. Seventeen baseline predictors were also examined. RESULTS: Data
      were obtained from 201 (96 %) patients, 17 of whom had died. Only 73 (36 %) had
      no DSM diagnosis at the time of follow-up. Using univariate and stepwise multiple
      linear regression those with cothymia, personality disorder, recurrent episodes
      and greater baseline self-rated anxiety and depression ratings had a worse
      outcome than others; initial diagnosis did not contribute significantly to
      outcome and instability of diagnosis over time was much more common than
      consistency. CONCLUSION: Only two out of five people with the common neurotic
      disorders have a good outcome despite alleged advances in treatment. Those with
      greater mood symptoms and pre-morbid personality disorder have the least
      favourable outcome. It is suggested that greater attention be paid to the
      concurrent treatment of personality disorder and environmental factors rather
      than symptoms as these may be the real cause of apparent treatment resistance.

PMID- 15724871
TI  - Twelve-year course and outcome of bulimia nervosa.
AB  - BACKGROUND: Since little is known about the long-term course and outcome of
      bulimia nervosa, the authors designed a 12-year prospective longitudinal study
      with five cross-sectional assessments based on a large sample of consecutively
      treated females with bulimia nervosa (purging type) (BN-P). METHOD: One hundred
      and ninety-six females with BN-P were assessed (1) at the beginning of treatment,
      (2) at the end of treatment, (3) at 2-year follow-up, (4) at 6-year follow-up,
      and (5) at 12-year follow-up. In self-ratings as well as expert ratings based on
      interviews we assessed specific eating-disorder and general psychopathology.
      RESULTS: The general pattern of results over time showed substantial improvement
      during treatment, slight (in most cases non-significant) decline during the first
      two years after the end of treatment, and further improvement and stabilization
      until 12-year follow-up. At that point the majority of patients (70.1 %) showed
      no major DSM-IV eating disorder, 13.2% had eating disorders not otherwise
      specified, 10.1 % had BN-P and 2% had died. Very few had undergone transition to
      anorexia nervosa or binge-eating disorders. Logistic regression analyses showed
      that psychiatric co-morbidity was the best and most stable predictor for eating
      disorder outcome at 2, 6 and 12 years. CONCLUSIONS: Course and outcome of BN-P
      was generally more favourable than for anorexia nervosa.

PMID- 15724872
TI  - Personality characteristics of women before and after recovery from an eating
      disorder.
AB  - BACKGROUND: Previous studies of personality characteristics in women with eating
      disorders primarily have focused on women who are acutely ill. This study
      compares personality characteristics among women who are ill with eating
      disorders, recovered from eating disorders, and those without eating or other
      Axis I disorder pathology. METHOD: Female participants were assessed for
      personality characteristics using the Temperament and Character Inventory (TCI):
      122 with anorexia nervosa (AN; 77 ill, 45 recovered), 279 with bulimia nervosa
      (BN; 194 ill, 85 recovered), 267 with lifetime histories of both anorexia and
      bulimia nervosa (AN + BN; 194 ill, 73 recovered), 63 with eating disorder not
      otherwise specified (EDNOS; 31 ill, 32 recovered), and 507 without eating or Axis
      I disorder pathology. RESULTS: Women ill with all types of eating disorders
      exhibited several TCI score differences from control women, particularly in the
      areas of novelty-seeking, harm avoidance, self-directedness, and cooperativeness.
      Interestingly, women recovered from eating disorders reported higher levels of
      harm avoidance and lower self-directedness and cooperativeness scores than did
      normal control women. CONCLUSIONS: Women with eating disorders in both the ill
      and recovered state show higher levels of harm avoidance and lower self
      directedness and cooperativeness scores than normal control women. Although
      findings suggest that disturbances may be trait-related and contribute to the
      disorders' pathogenesis, additional research with more representative community
      controls, rather than our pre-screened, normal controls, is needed to confirm
      these impressions.

PMID- 15724873
TI  - Psychological health of Australian veterans of the 1991 Gulf War: an assessment
      using the SF-12, GHQ-12 and PCL-S.
AB  - BACKGROUND: Elevated rates of psychological morbidity and symptomatology have
      been widely reported in 1991 Gulf War veterans. The present study used brief self
      report instruments to compare the psychological health of Australian Gulf War
      veterans with that of a randomly sampled military comparison group. METHOD: The
      12-item Short Form Health Survey (SF-12), 12-item General Health Questionnaire
      (GHQ-12), Posttraumatic Stress Disorder Checklist--Specific (PCL-S) and Military
      Service Experience (MSE) questionnaire were administered to 1424 male Australian
      Gulf War veterans and 1548 male Australian Defence Force members who were
      operational at the time of the Gulf War conflict, but were not deployed there.
      RESULTS: The Gulf War veterans exhibited poorer psychological health, as measured
      by the above three instruments, than the comparison group members. For Gulf War
      veterans, the number of stressful experiences, as measured by the MSE
      questionnaire, was correlated with scores on the three instruments. SF-12 mental
      health component summary scores and PCL-S caseness, but not GHQ-12 caseness,
      differed significantly between Gulf War veterans and comparison group members who
      had been on at least one active deployment. CONCLUSIONS: More than a decade after
      the 1991 Gulf War, Australian Gulf War veterans are exhibiting higher levels of
      current (past month) psychological ill-health, as measured using the GHQ-12 and
      PCL-S, as well as lower mental health status, as measured by the SF-12, than the
      comparison group. Although not a replacement for formal psychiatric diagnosis,
      instruments such as those above may aid in the assessment of veterans'
      psychological health.

PMID- 15724874
TI  - Anxiety and depression in parents 4-9 years after the loss of a child owing to a
      malignancy: a population-based follow-up.
AB  - BACKGROUND: Some consider the loss of a child as the most stressful life event.
      When the death is caused by a malignancy, the parents are commonly exposed not
      only to their own loss, but also to the protracted physical and emotional
      suffering of the child. We investigated parental risk of anxiety and depression 4
      9 years after the loss of a child owing to a malignancy. METHOD: In 2001, we
      attempted to contact all parents in Sweden who had lost a child due to a
      malignancy during 1992--1997. We used an anonymous postal questionnaire and
      utilized a control group of non-bereaved parents with a living child. RESULTS:
      Participation among bereaved parents was 449/561 (80 %); among non-bereaved
      457/659 (69%). We found an increased risk of anxiety (relative risk 1.5, 95 %
      confidence interval 1.1-1.9) and depression (relative risk 1.4, 95 % confidence
      interval 1.1-1.7) among bereaved parents compared with non-bereaved. The risk of
      anxiety and depression was higher in the period 4-6 years after bereavement than
      in the 7-9 years period, during which the average excess risks approached zero.
      Psychological distress was overall higher among bereaved mothers and loss of a
      child aged 9 years or older implied an increased risk, particularly for fathers.
      CONCLUSIONS: Psychological morbidity in bereaved parents decreases to levels
      similar to those among non-bereaved parents 7-9 years after the loss. Bereaved
      mothers and parents who lose a child 9 years or older have on average an excess
      risk for long-term psychological distress.

PMID- 15724875
TI  - Co-morbidity and stability of melancholic features in DSM-IV major depressive
      disorder.
AB  - BACKGROUND: The descriptive validity of the melancholic features specifier of the
      DSM-IV major depressive disorder (MDD) is uncertain. Little is known about its
      relationship to psychiatric co-morbidity, stability across episodes, or strength
      in predicting course of illness. METHOD: The Vantaa Depression Study (VDS) is a
      prospective, naturalistic cohort study of 269 patients with a new episode of DSM
      IV MDD who were interviewed with SCAN and SCID-II between 1 February 1997 and 31
      May 1998, and again at 6 and 18 months. Ninety-seven (36%) MDD patients met DSM
      IV criteria for the melancholic features specifier, and were contrasted with 172
      (64 %) subjects with a non-melancholic MDD. The duration of the index episode was
      examined using a life chart. RESULTS: We found no difference in rates of any
      current co-morbid Axis I or II disorders between melancholic and non-melancholic
      depressed patients. Of those who had melancholic features at the index episode
      and subsequent episodes during the 18-month follow-up, only 22 % (5/23) presented
      melancholic features during the latter. The non-melancholic subtype switched to
      melancholic in 25 % (8/32) of cases. Differences in the course of melancholic and
      non-melancholic depression were very minor. CONCLUSIONS: The descriptive validity
      of the DSM-IV melancholic features specifier may be questionable in MDD. There
      appear to be no major differences in current co-morbidity, or course of
      depression between melancholic and non-melancholic patients. The consistency of
      DSM-IV melancholic features across episodes appears weak.

PMID- 15724876
TI  - Impaired divided attention predicts delayed response and risk to relapse in
      subjects with depressive disorders.
AB  - BACKGROUND: This study addresses the complex relationship between cognitive
      function and the course of depression. METHOD: A sample of patients (n=73) in a
      depressive episode (major depression or bipolar disorder) was tested with a
      comprehensive battery of attention and executive tasks at both admission and
      discharge. In addition, response to pharmacological treatment and remission was
      assessed with standardized rating scales. Nineteen patients, recovered from
      depression, were re-investigated 6 months after discharge to determine whether
      specific cognitive parameters were related to subsequent relapse. RESULTS: On
      admission, patients were impaired in almost all cognitive tasks. At discharge, we
      found a significant reduction in psychopathology, but only marginal cognitive
      improvements. Non-responders after 4 weeks of antidepressive medication and
      subjects who did not achieve remission prior to discharge were specifically
      impaired in divided attention on admission (p < 0.05). In addition, a trend was
      found for the association between impaired divided attention at discharge and an
      elevated risk to relapse (p < 0.10). CONCLUSIONS: We observed generalized
      cognitive impairment in most cognitive domains in acute depression. Cognitive
      impairments were still within abnormal ranges at discharge but less distinct.
      Divided attention performance predicted response to treatment, remission of
      symptoms, and risk to relapse. Impaired divided attention capacity can be
      explained either by reduced attentional resources or impaired activation and/or
      top-down control of attentional resources by the central executive.

PMID- 15724877
TI  - Asthma and depressive and anxiety disorders among young persons in the community.
AB  - BACKGROUND: The objectives of the study were to examine linkages between asthma
      and depressive and anxiety disorders in a birth cohort of over 1000 young persons
      studied to the age of 21 years. Specifically, the study aimed to ascertain the
      extent to which associations between asthma and depressive and anxiety disorders
      could be explained by non-observed fixed confounding factors. METHOD: Asthma and
      depressive and anxiety disorders were measured prospectively over the course of a
      21-year longitudinal study. Fixed effects logistic regression models were used to
      determine the relationship between asthma and depressive and anxiety disorders,
      adjusting for potentially confounding factors. RESULTS: Asthma in adolescence and
      young adulthood was associated with increased likelihood of major depression (OR
      1.7, 95 % CI 1.3-2.3), panic attacks (OR 1.9, 95 % CI 1.3-2.8), and any anxiety
      disorder (OR 1.6, 95% CI 1.2-2.2). Associations between asthma and depressive and
      anxiety disorders were adjusted for confounding factors using a fixed effects
      regression model which showed that, after control for fixed confounding factors,
      asthma was no longer significantly related to major depression (OR 1.1), panic
      attacks (OR 1.1), or any anxiety disorder (OR 1.2). Additional post hoc analyses
      suggested that exposure to childhood adversity or unexamined familial factors may
      account for some of the co-morbidity of asthma and depressive and anxiety
      disorders. CONCLUSIONS: These results confirm and extend previous findings by
      documenting elevated rates of depressive and anxiety disorders among young adults
      with asthma, compared with their counterparts without asthma, in the community.
      The weight of the evidence from this study suggests that associations between
      asthma and depressive and anxiety symptoms may reflect effects of common factors
      associated with both asthma and depressive and anxiety disorders, rather than a
      direct causal link. Future research is needed to identify the specific factors
      underlying these associations.

PMID- 15724878
TI  - Childhood sexual abuse, stressful life events and risk for major depression in
      women.
AB  - BACKGROUND: In animals, early trauma can produce long-lasting changes in
      sensitivity to the pathogenic effects of stress. To explore whether similar
      processes occur in humans, we examine whether childhood sexual abuse (CSA) in
      women alters sensitivity in adulthood to the depressogenic effects of stressful
      life events (SLEs). METHOD: A history of CSA was obtained from a population-based
      sample of 1404 female adult twins. Cox Proportional hazard models were used to
      predict onsets of episodes of DSM-III-R major depression (MD) in the past year
      from previously assessed levels of neuroticism (N), CSA and past-year SLEs scored
      on long-term contextual threat. RESULTS: In the best-fit model, onset of MD was
      predicted by CSA, SLEs and N. Individuals with CSA (and especially with severe
      CSA) had both an overall increased risk for MD and a substantially increased
      sensitivity to the depressogenic effects of SLEs. A 'dose-response' relationship
      between severity of CSA and sensitivity to SLEs was clearer in those with low to
      average levels of N than in those with high levels of N. CONCLUSION: As
      documented with physiological responses to a standardized laboratory stressor,
      CSA increases stress sensitivity in women in a more naturalistic setting. Both
      genetic and early environmental risk factors can produce long-term increase in
      the sensitivity of individuals to depressogenic life experiences.

PMID- 15724879
TI  - Juvenile- versus adult-onset depression: multiple differences imply different
      pathways.
AB  - BACKGROUND: Several sources of heterogeneity in major depression have been
      identified. These include age of onset, presence of co-morbid disorders, and
      history of childhood sexual abuse. This study examined these factors in the
      context of the contrast between onset of depression in young women before and
      after age 16. METHOD: Sampling was carried out in two phases. In the first,
      questionnaires were sent to women aged 25-36 in five primary care practices.
      Second-phase subjects for interview (n = 197) were drawn from three strata
      defined on the basis of childhood adversities. Interviews conducted and rated
      independently assessed (1) recalled childhood experiences, psychopathology and
      parental psychiatric disorder, and (2) adult personality functioning and adult
      lifetime psychopathology. Frequencies of predictor and response variables, effect
      estimates and their confidence intervals were weighted back to the general
      population questionnaire sample. RESULTS: Compared with adult-onset depression,
      juvenile-onset adult depression was associated with co-morbid childhood
      psychopathology and peer problems, poor parental care, and childhood sexual abuse
      involving actual or attempted intercourse; in adult life there were higher levels
      of co-morbid psychiatric disorders, and personality dysfunction. The adult-onset
      depression group was characterized by a history of contact childhood sexual abuse
      without actual or attempted intercourse, and to a lesser extent, poor parental
      care. CONCLUSIONS: The juvenile- versus adult-onset distinction appears to be
      important to heterogeneity in adult depression, implicating different individual
      and environmental factors during childhood, and different mechanisms in adult
      life.

PMID- 15724880
TI  - Memory complaints in a community sample aged 60-64 years: associations with
      cognitive functioning, psychiatric symptoms, medical conditions, APOE genotype,
      hippocampus and amygdala volumes, and white-matter hyperintensities.
AB  - BACKGROUND: Previous research has found that depression is a major cause of
      memory complaints. However, there is evidence that memory complaints also weakly
      predict cognitive decline and dementia. The present study examined a range of
      possible determinants of memory complaints, covering psychiatric and personality
      factors, medical history, cognitive test performance, and biological risk factors
      for dementia (APOE genotype, hippocampus and amygdala volumes, and white-matter
      hyperintensities). METHOD: A community survey was carried out with 2546 persons
      aged 60-64 years living in Canberra and Queanbeyan, Australia. Participants were
      asked about memory problems which interfered with daily life and whether medical
      help had been sought. A randomly selected subsample of 476 persons was given a
      brain MRI scan. RESULTS: Participants with memory complaints were found to have
      poorer memory test performance, more depression and anxiety symptoms, have higher
      scores on personality traits involving negative affect, and to have worse
      physical health. Multivariate analyses showed that measures of cognitive
      performance did not make a unique contribution to the prediction of memory
      complaints above that of the other categories of predictors. Those with memory
      complaints did not differ on any of the biological risk factors for dementia.
      CONCLUSION: In a community sample aged 60-64 years, memory complaints were most
      closely related to psychiatric symptoms, personality characteristics and poor
      physical health. There was no evidence of brain changes indicating early
      dementia.

PMID- 15724881
TI  - Depression in elderly homecare patients: patient versus informant reports.
AB  - BACKGROUND: This study compares patient and informant reports of depressive
      disorders in a community sample of elderly medical homecare patients. The
      associations between specific patterns of agreement/disagreement and other
      patient and informant characteristics are examined. METHOD: A random sample of
      355 elderly medical homecare patients and their informants were interviewed using
      the current mood section of the Structured Clinical Interview for DSM-IV (SCID).
      RESULTS: Thirty-seven patients (10.4 %) reported a depressive disorder (major or
      subsyndromal) that was also identified by their informant while 27 (7.6 %)
      patients self-reported depression that the informant did not identify. There were
      250 patients (70.4 %) who were not depressed according to both patient and
      informant report and 41 patients (11.5%) were identified as depressed by
      informant report alone. Patients identified as depressed by informant report
      alone were similar to patients who self-reported depression on a number of the
      sociodemographic and clinical correlates of depression, but had significantly
      poorer performance on items assessing orientation and short-term recall. These
      patients also had poorer functioning in a number of domains (social, cognitive,
      and functional) when compared with patients who were not depressed according to
      both the patient and informant. Finally, patients with younger informants were
      more likely to be identified as depressed by their informant. CONCLUSIONS:
      Obtaining informant reports of depression may be a useful method for detecting
      clinically significant cases of late-life depression that would otherwise be
      missed when relying only on patient report.

PMID- 15724882
TI  - Genetic effects on alcohol dependence risk: re-evaluating the importance of
      psychiatric and other heritable risk factors.
AB  - BACKGROUND: Genetic influences have been shown to play a major role in
      determining the risk of alcohol dependence (AD) in both women and men; however,
      little attention has been directed to identifying the major sources of genetic
      variation in AD risk. METHOD: Diagnostic telephone interview data from young
      adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox
      regression models were fitted to interview data from a total of 2708 complete
      twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ
      female/male pairs). Structural equation models were fitted to determine the
      extent of residual genetic and environmental influences on AD risk while
      controlling for effects of sociodemographic and psychiatric predictors on risk.
      RESULTS: Risk of AD was increased in males, in Roman Catholics, in those
      reporting a history of major depression, social anxiety problems, and conduct
      disorder, or (in females only) a history of suicide attempt and childhood sexual
      abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox
      religion, in those who reported weekly church attendance, and in university
      educated males. After allowing for the effects of sociodemographic and
      psychiatric predictors, 47 % (95% CI 28-55) of the residual variance in
      alcoholism risk was attributable to additive genetic effects, 0% (95% CI 0-14) to
      shared environmental factors, and 53% (95% CI 45-63) to nonshared environmental
      influences. CONCLUSIONS: Controlling for other risk factors, substantial residual
      heritability of AD was observed, suggesting that psychiatric and other risk
      factors play a minor role in the inheritance of AD.

PMID- 15724883
TI  - Interaction of genetic risk and adoptive parent communication deviance:
      longitudinal prediction of adoptee psychiatric disorders.
AB  - BACKGROUND: In the Finnish Adoptive Family Study of Schizophrenia, adoptee
      thinking disorders have been shown to be a joint effect of genetic liability for
      schizophrenia spectrum disorders and adoptive rearing-parent communication
      patterns. However, longitudinal predictions of clinical psychiatric disorders of
      the adoptees have not been reported. METHOD: Adoptees (n = 109) who had no DSM
      III-R disorder at initial assessment (median age 18 years) were selected from the
      total sample of the Finnish Adoption Study of Schizophrenia. They were defined as
      at high versus low genetic risk based upon the lifetime diagnoses of their
      biological, adopting-away mothers - schizophrenia spectrum disorder versus no
      spectrum disorder. At initial assessment, adoptive rearing parents were
      independently evaluated from tape-recorded Rorschach protocols scored as
      manifesting either high or low Communication Deviance (CD), a composite index of
      communication patterns that distract and befuddle listeners. Adoptees were
      independently re-diagnosed after a median interval of 14 years and followed-up
      from national registers for an additional 7 years. RESULTS: The main effects of
      genetic liability (G) and CD of the adoptive parents (E), each taken separately,
      predicted significantly for psychiatric disorders of the adoptees as adults.
      However, when G, E, and their joint interaction effect were entered into the same
      logistic model, only the interaction effect was significant. The sample included
      seven adoptees with schizophrenia spectrum disorders, but a separate analysis to
      predict them was non-significant. CONCLUSION: Genetic liability for schizophrenia
      spectrum disorder and an adoptive family rearing variable interact, predicting
      longitudinally and significantly to broadly defined adoptee psychiatric disorder.

PMID- 15724885
TI  - Cohabiting unions, repartnering and mental health.
AB  - BACKGROUND: A considerable body of research has established that transitions out
      of marriage are generally deleterious for mental health and some have examined
      transitions out of cohabitation. In this study we depart from these established
      areas to investigate the effects of poor mental health on the duration and
      outcome of cohabitations and on the time to, and likelihood of, repartnering
      after both cohabitation and marriage. METHOD: Samples came from the British
      Household Panel Survey, 1991--2001. These were: (1) 447 cohabiting spells; (2)
      5571 paired person-years during cohabitation; (3) 508 spells after cohabitation;
      (4) 1197 person-year observations within those spells; (5) 869 spells after
      marriage; and (6) 2736 person-year observations within those spells. Life tables,
      log-rank tests, multinomial logit and proportional hazard models were used.
      Mental health was measured by the 12-item General Health Questionnaire. RESULTS:
      Poor mental health increased the risk of dissolving a cohabiting union for both
      men and women. Poor mental health reduced the risk of repartnering after a
      cohabiting union but had no effect on the risk of repartnering after a marriage.
      Other factors such as past marital status, age and parental status also had
      significant effects. CONCLUSIONS: This study provides evidence that poor mental
      health during a cohabiting union increases the chances of that union dissolving
      instead of turning into marriage and poorer mental health immediately after a
      transition out of a cohabiting union is associated with reduced chances of
      repartnering.

PMID- 15724884
TI  - Common mental disorders and ethnicity in England: the EMPIRIC study.
AB  - BACKGROUND: There is little population-based evidence on ethnic variation in the
      most common mental disorders (CMD), anxiety and depression. We compared the
      prevalence of CMD among representative samples of White, Irish, Black Caribbean,
      Bangladeshi, Indian and Pakistani individuals living in England using a
      standardized clinical interview. METHOD: Cross-sectional survey of 4281 adults
      aged 16-74 years living in private households in England. CMD were assessed using
      the Revised Clinical Interview Schedule (CIS-R), a standardized clinical
      interview. RESULTS: Ethnic differences in the prevalence of CMD were modest, and
      some variation with age and sex was noted. Compared to White counterparts, the
      prevalence of CMD was higher to a statistically significant degree among Irish
      [adjusted rate ratios (RR) 2.09, 95% CI 1.16-2.95, p = 0.02] and Pakistani
      (adjusted RR 2.38, 95 % CI 1.25-3.53, p = 0.02) men aged 35-54 years, even after
      adjusting for differences in socio-economic status. Higher rates of CMD were also
      observed among Indian and Pakistani women aged 55-74 years, compared to White
      women of similar age. The prevalence of CMD among Bangladeshi women was lower
      than among White women, although this was restricted to those not interviewed in
      English. There were no differences in rates between Black Caribbean and White
      samples. CONCLUSIONS: Middle-aged Irish and Pakistani men, and older Indian and
      Pakistani women, had significantly higher rates of CMD than their White
      counterparts. The very low prevalence of CMD among Bangladeshi women contrasted
      with high levels of socio-economic deprivation among this group. Further study is
      needed to explore reasons for this variation.

PMID- 15724886
TI  - Self-monitoring in patients with schizophrenia.
AB  - BACKGROUND: The present study investigated whether a failure of self-monitoring
      contributes to core syndromes of schizophrenia. METHOD: Three groups of patients
      with a DSM-IV diagnosis of schizophrenia (n = 27), with either prominent paranoid
      hallucinatory or disorganization syndrome, or without these symptoms, and a
      matched healthy control group (n = 23) drew circles on a writing pad connected to
      a PC monitor. Subjects were instructed to continuously monitor the relationship
      between their hand movements and their visual consequences. They were asked to
      detect gain changes in the mapping. Self-monitoring ability and the ability to
      automatically correct movements were assessed. RESULTS: Patients with either
      paranoid-hallucinatory syndrome or formal thought disorder were selectively
      impaired in their ability to detect a mismatch between a self-generated movement
      and its consequences, but not impaired in their ability to automatically
      compensate for the gain change. CONCLUSIONS: These results support the claim that
      a failure of self-monitoring may underlie the core symptoms of schizophrenia.

PMID- 15724887
TI  - Interpersonal and role-related schema influence the relationship with the
      dominant 'voice' in schizophrenia: a comparison of three models.
AB  - BACKGROUND: Auditory hallucinations in psychosis often contain critical
      evaluations of the voice-hearer (for example, attacks on self-worth). A voice
      hearer's experience with their dominant voice is a mirror of their social
      relationships in general, with experiences of feeling low in rank to both voices
      and others being associated with depression. However, the direction of the
      relationship between psychosis, depression and feeling subordinate is unclear.
      METHOD: Covariance structural equation modelling was used with data from 125
      participants diagnosed with schizophrenia to compare three 'causal' models: (1)
      that depression leads to the appraisal of low social rank, voice power and
      distress; (2) that psychotic illness leads to voice activity (frequency,
      audibility), which in turn leads to depression and the appraisal of voices'
      power; (3) our hypothesized model, that perceptions of social rank and social
      power lead to the appraisal of voice power, distress and depression. RESULTS:
      Findings supported model 3, suggesting that the appraisal of social power and
      rank are primary organizing schema underlying the appraisal of voice power, and
      the distress of voices. CONCLUSIONS: Voices can be seen to operate like external
      social relationships. Voice content and experience can mirror a person's social
      sense of being powerless and controlled by others. These findings suggest
      important new targets for intervention with cognitive and social therapy.

PMID- 15724888
TI  - Perspective-taking deficits in people with schizophrenia spectrum disorders: a
      prospective investigation.
AB  - BACKGROUND: This study examined data from a Danish prospective longitudinal
      project in attempt to address the state/trait controversy regarding theory of
      mind deficits in schizophrenia. Deficits in perspective-taking--a component of
      theory of mind--were investigated prospectively among children who developed
      schizophrenia spectrum disorders as adults in comparison to children who did not
      develop schizophrenia spectrum disorders. METHOD: A total of 265 high risk and
      control subjects were studied in 1972. At the time of initial assessment, the
      Role-Taking Task (RTT) was administered. Two hundred and forty-two of these
      children were evaluated in 1992 during follow-up examinations. Sixteen developed
      schizophrenia, 10 developed a schizophrenia spectrum disorder, 70 had outcomes of
      other psychopathology, and 146 did not develop a mental illness. RESULTS:
      Children who later developed schizophrenia or a schizophrenia spectrum disorder
      had lower RTT scores, controlling for verbal IQ and age, compared to those who
      did not develop any mental illness. Although in the expected direction, RTT
      scores for those with schizophrenia spectrum disorders were not significantly
      different from those who developed a non-psychotic disorder. CONCLUSIONS:
      Deficits in perspective-taking among children who later developed schizophrenia
      spectrum disorders suggest that a facet of theory of mind is impaired prior to
      development of schizophrenia. Our findings lend support to the hypothesis that
      theory of mind deficits in schizophrenia are trait markers of the disorder.

PMID- 15724889
TI  - Severe congenital ptosis: we want your help!

PMID- 15724890
TI  - Treating retinopathy of prematurity.

PMID- 15724891
TI  - What's your diagnosis? Ciliary body medulloepithelioma.

PMID- 15724892
TI  - Are there ocular effects of inhaled steroid therapy?

PMID- 15724893
TI  - Management of Duane retraction syndrome.
AB  - BACKGROUND: Duane retraction syndrome is the most common cause of congenital
      aberrant ocular innervation. We report referral practices, clinical
      characteristics and complications, prevalence of congenital and familial
      anomalies, and management outcomes from a clinic-based series. METHODS:
      Retrospective clinic-based study of 65 patients with Duane retraction syndrome
      seen between January 1994 and March 2004. RESULTS: The majority of patients were
      girls with type I Duane retraction syndrome associated with esotropia in primary
      gaze. Twenty percent of cases were complicated by absent binocular stereoacuity
      and 16.9% had amblyopia. Family history of any ocular disorder was reported in
      38.5% of cases, while an associated congenital abnormality was found in 46% of
      patients. There was a significant delay between the age when ocular abnormalities
      were first noticed and the age when patients presented at our tertiary referral
      center (P < .001). Twenty-two percent of patients underwent surgical correction
      at a mean age of 6 years. Most procedures were unilateral or bilateral medial or
      lateral rectus recessions. Postoperative ocular alignment < or = 15 prism
      diopters (PD) was achieved in 86% of cases, with 50% of cases having < or = 5 PD.
      CONCLUSIONS: Amblyopia and absent binocular stereo vision affected one in five
      patients with Duane retraction syndrome. There was significant delay between
      identification of an abnormality and presentation at the eye clinic.

PMID- 15724894
TI  - Vitrectomy for dense vitreous hemorrhage in infancy.
AB  - PURPOSE: To report clinical data, including etiology and visual outcome, in
      newborns requiring vitrectomy for dense vitreous hemorrhage. METHODS: In this
      retrospective case series, we surveyed subscribers to the American Association
      for Pediatric Ophthalmology and Strabismus ListServe regarding patients under
      their care. RESULTS: A total of 28 eyes of 21 patients were included. Most common
      etiologies were thrombocytopenia, shaken baby syndrome, and birth trauma. In 9
      cases (12 eyes), the vitreous hemorrhage was idiopathic. Mean time between
      diagnosis and surgery was 1.4 months. Complications included strabismus,
      cataract, glaucoma, high myopia, and retinal detachment. Recognition visual
      acuities were available for 8 eyes: 20/25 (2 eyes), 20/30, 20/40 (2 eyes), 20/60
      (2 eyes), and 20/100. One eye had no light perception. CONCLUSIONS: The
      etiologies encountered in our patients were similar to those reported previously.
      Visual outcomes were much worse in cases with retinal complications. Other
      patients had better visual outcomes. Despite potential surgical and postoperative
      complications, this series demonstrates favorable visual outcomes can be achieved
      following early vitrectomy in this setting.

PMID- 15724895
TI  - Cataract and ocular hypertension in children on inhaled corticosteroid therapy.
AB  - PURPOSE: To ascertain the incidence of posterior subcapsular cataract and ocular
      hypertension in a cohort of children < or = 12 years on inhaled steroid therapy.
      PATIENTS AND METHODS: In this prospective study, a detailed history regarding
      corticosteroid therapy was obtained for children attending an asthma clinic. The
      presence and type of lens changes (cataract) was recorded and intraocular
      pressure (IOP) was measured. The children underwent another eye examination 2
      years later. RESULTS: Ninety-five patients were enrolled in the study. Mean
      patient age was 7 +/- 3 years, and mean duration of inhaled steroid therapy was 2
      +/- 1 years. Thirty-six percent of patients received inhaled steroids
      exclusively, 61% received inhaled steroids with a short course of oral steroids,
      and 3% received inhaled steroids with a long course of oral steroids. Only 3 (3%)
      patients had cortical changes that were not visually significant, and none had
      posterior subcapsular or nuclear cataract. There was no significant differences
      between children with cataract and those without cataract with respect to age;
      duration of asthma; and duration, average daily dose, and cumulative dose of
      inhaled steroids. IOP ranged from 11 to 20 mm Hg (mean, 16 +/- 3 mm Hg). None of
      the children had ocular hypertension or glaucoma. Ninety patients underwent eye
      examination 2 years later; none was found to develop posterior subcapsular
      cataract or increased IOP. CONCLUSION: This study indicates the use of inhaled
      steroids in children with asthma is probably safe as far as not inducing
      posterior subcapsular cataract or ocular hypertension.

PMID- 15724897
TI  - Corneal transplants for the treatment of congenital corneal opacities.
AB  - PURPOSE: To describe the results of corneal transplants in infants and young
      children with congenital corneal disorders. METHODS: The charts of 38 children
      who underwent corneal transplantation for congenital corneal opacities from 1988
      to 1999 at the Hospital for Sick Children, Toronto, Ontario, were reviewed.
      Parameters reviewed included indication, age at diagnosis and surgery, graft
      size, graft clarity, repeat surgery, glaucoma pre- and postsurgery, visual
      acuity, and refraction. RESULTS: Thirty-eight children (63 eyes) underwent 86
      corneal transplants. The four most common indications for surgery included
      posterior polymorphous dystrophy, Peters anomaly, congenital glaucoma, and
      sclerocornea. Mean follow-up was 40.4 +/- 30.2 months (range, 2-111 months).
      Seventy-eight percent of the grafts were clear at the final follow-up visit.
      There were 23 repeat grafts in the entire group. CONCLUSIONS: The overall success
      rate of graft clarity was 78% for children undergoing corneal transplantation for
      congenitally opaque corneas. Best results were achieved in patients with
      posterior polymorphous dystrophy, followed by patients with Peters anomaly.
      Sclerocornea and congenital glaucoma carried a 50% chance of success, with
      repeated transplants needed for many of the eyes.

PMID- 15724896
TI  - Extraocular muscle cysticercosis: clinical presentations and outcome of
      treatment.
AB  - PURPOSE: To report various clinical presentations and treatment outcomes in a
      series of patients with extraocular muscle cysticercosis. METHODS: This
      retrospective study reviewed the charts of 43 patients diagnosed with extraocular
      muscle cysticercosis with computed tomography and orbital B-scan ultrasonography
      between January 1991 and December 2002. Clinical presentation, results of
      investigations, treatment, and outcome were recorded. RESULTS: The superior
      rectus was the most commonly affected extraocular muscle. Restricted ocular
      motility was present in 88% of patients, and inflammatory signs were noted in the
      involved quadrant in 70% of patients. Eleven patients were treated with oral
      albendazole alone and 31 patients were treated with oral albendazole and
      prednisolone. Four extraocular muscle cysts were excised surgically, and five
      extruded spontaneously. Inflammatory signs subsided in all patients, and residual
      restriction of ocular motility was seen in 16 (50%) of 32 patients at a mean
      follow-up of 5 months. Type of treatment made no significant difference in the
      ocular motility outcome. CONCLUSIONS: Extraocular muscle cysticercosis should be
      considered in patients who present with restricted ocular motility and
      inflammatory signs. The direction of motility restriction does not indicate the
      muscle involved. Residual restriction of ocular motility is common despite the
      addition of corticosteroids to albendazole therapy.

PMID- 15724898
TI  - Ophthalmologic findings in cerebrofaciothoracic dysplasia.
AB  - We describe the ophthalmologic findings in two cases of cerebrofaciothoracic
      dysplasia, a rare syndrome characterized by facial dysmorphism, multiple
      malformations of the vertebrae and ribs, and significant mental retardation. Both
      affected individuals are members of the same family and have epicanthal folds and
      hypertelorism. In addition, one patient has bilateral bull's eye maculopathy,
      which may represent an additional severe manifestation of cerebrofaciothoracic
      dysplasia syndrome.

PMID- 15724899
TI  - Severe amblyopia of the sound eye resulting from atropine therapy combined with
      optical penalization.
AB  - The potential amblyogenic effect to the sound eye of atropine combined with
      optical penalization is powerful, and frequent patient monitoring is necessary
      when using this therapy. We report two cases of amblyopia developing in the
      previously sound eye as a result of noncompliance during atropine therapy
      combined with optical penalization. Both cases required active treatment to
      correct the reverse amblyopia. Vision returned to normal in one patient, while
      the second patient was lost to follow-up with poor acuity.

PMID- 15724900
TI  - Pediatric ophthalmologic findings of Cohen syndrome in twins.
AB  - We present the clinical findings and follow-up data of male twins with Cohen
      syndrome. The most characteristic ophthalmologic findings were down-slanting
      eyelids, lens opacities, chorioretinal dystrophy, pigmentary retinal deposits,
      pale disk, and bull's eye maculae.

PMID- 15724901
TI  - Ophthalmic herpes zoster in an 18-month-old child.
AB  - We present a case of herpes zoster ophthalmicus in an 18-month-old child. Early
      exposure to varicella zoster virus while being breast-fed appears to account for
      this clinical presentation. The incidence of herpes zoster in children younger
      than age 2 years is discussed.

PMID- 15724902
TI  - Congenital orbital teratoma.

PMID- 15724903
TI  - False memory across languages: implicit associative response vs fuzzy trace
      views.
AB  - We investigated false recognition across languages using the Deese-Roediger
      McDermott (DRM) paradigm. A group of English-French bilinguals studied lists of
      converging associates, some lists in English and some in French, and then
      performed a recognition test containing studied list items and nonstudied
      critical lures whose language matched or mismatched the language at study.
      Participants were instructed to answer old only if the test cue was in the same
      language as the studied word. The results yielded a robust false memory rate both
      within-language and across-languages. The effect of the study-test language shift
      was much larger for list items than for critical lures. This finding suggests
      that memory representations for critical lures contain primarily semantic gist
      traces and little surface information, and hence is more consistent with the
      fuzzy trace view than with the implicit associative response view. In sum, the
      study demonstrates the existence of false memory across languages, and provides
      information about the memory traces underlying veridical and illusory
      recognition.

PMID- 15724904
TI  - Remembering a nuclear accident in Japan: did it trigger flashbulb memories?
AB  - Flashbulb memories are vivid memories of the details surrounding the discovery of
      an emotional event. We investigated whether the nuclear accident that occurred in
      Japan in 1999 produced flashbulb memories among people who lived near the
      accident site. A questionnaire was distributed twice (approximately 3 weeks after
      the accident and 1 year later) to (1) the residents of the communities
      surrounding the accident site, (2) the students at a university near the accident
      site, and (3) the students at two universities far away from the accident site.
      Flashbulb memory holders were defined as those individuals who showed consistent
      memories between test and retest. The results indicated that only a small
      percentage of participants formed flashbulb memories. Further, no age-related
      decline was found. Flashbulb memories were distinguished by perfect or near
      perfect scores on four attributes: source, place, activity, and people. The
      results also indicated that the ratings on emotional reactions, personal
      consequentiality, and surprise did not differentiate between the flashbulb and
      non-flashbulb memory holders. In contrast, the flashbulb memory holders reported
      rehearsing more than the non-flashbulb memory holders. These results supported
      the notion that flashbulb memories are formed through rehearsal rather than at
      encoding. However, it is also possible that rehearsal was a result of the
      flashbulb memory.

PMID- 15724905
TI  - Own-age biases in verbal person memory.
AB  - Two experiments examined own-age biases in younger adults', older adults', and
      children's verbal person memory. In line with findings from face recognition
      studies, Experiment 1 showed that younger adults had a better recall of own-age
      than of other-age targets, while older adults were unaffected by target age.
      Participants' self-reported interest in targets did not predict target memory.
      Experiment 2, which examined children's and younger adults' memory of own- and
      other-age targets, showed an own-age advantage in children's but not in younger
      adults' verbal person memory. Differences in expertise of own-/other-age targets,
      in combination with a development of expertise throughout the lifespan, may
      account for the findings, although alternative explanations should be considered.
      Implications for theory and practice are discussed.

PMID- 15724906
TI  - When nothing is "off the record": exploring the theoretical implications of the
      continuous recording of cognitive process in memory.
AB  - This theoretical paper explores the idea of acropetal memory; arguing that
      representations emanating from all stages of processing an individual stimulus
      can be registered in memory and potentially available for recall. I describe
      Lansdale's (1998) HELM model of location memory as a suitable candidate theory
      within which to implement and test this idea. An exemplar model, HELM-2, is
      presented and examined against available data. This model provides a satisfactory
      account of the data and an elegant solution to some interesting puzzles. It also
      suggests that some retrieval failure can be attributed to interference from
      representations of a stimulus derived from early stages of processing and that
      this has much broader implications for modelling encoding, forgetting, and false
      memory.

PMID- 15724907
TI  - The earliest memory in individuals raised in either traditional and reformed
      kibbutz or outside the kibbutz.
AB  - In two studies we compared the age of traditional kibbutz members' first memories
      with the first memories of people raised in Israeli cities (Study 1) and of
      people who were raised in reformed kibbutzim (Study 2). Building on the socio
      cultural model of autobiographical memory, we predicted and found that children
      raised in the traditional kibbutz, not by their parents, but by a metapelet, had
      a significantly later onset of autobiographical memory than children raised in
      reformed kibbutzim or outside the kibbutz, who were under the primary care of
      their parents. We also examined gender differences in reporting the earliest
      memory. No gender differences were observed within each setting in the age of the
      earliest memory, but consistent with past research, memories reported by females
      were more elaborate than those reported by males.

PMID- 15724908
TI  - Towards a bio-psycho-social model of autobiographical memory.
AB  - Self-awareness and identity are important cornerstones of thinking in social
      psychology. On the basis of current knowledge and theories from the social,
      cultural, and biological sciences, this paper attempts to outline an integrative
      approach to the phenomena of memory and reminiscence. Reference to psychodynamic
      argumentation is made in addition, where appropriate. The central topic to our
      argumentation is autobiographical memory, which we analyse according to
      evolutionary, neuroscientific, and cultural findings. The emotional context and
      the ontogenetic development of reminiscences (or memories directly relating to
      one's own self) provide the preliminary framework for an integrated view which
      includes interactions between the life span, brain development, the social and
      cultural environment, and genetic predispositions.

PMID- 15724909
TI  - The effects of cue modality on the quality of personal memories retrieved.
AB  - We investigated the effect of cue modality on the specificity, speed, vividness,
      and age of autobiographical memory retrieval. Cues were presented as either an
      odour, a visual image, or a word label. Odour-cued memories were older, more
      likely to be categoric, and were slower to be retrieved. Few gender differences
      were found although females reported more vivid memories than males. We suggest
      that cue modality directly affects retrieval processes; odour cues are more
      likely to initiate a perceptual search strategy, in contrast to memories cued by
      visual images and words, which are usually conceptually/verbally mediated.

PMID- 15724910
TI  - The effects of conformity on recognition judgements.
AB  - Schneider and Watkins (1996) demonstrated that participants' recognition
      performance can be affected by responses generated by a confederate. However, it
      remains uncertain whether the confederate's responses actually change the
      participants' memories or whether participants simply attempt to conform to the
      confederate. The present experiments examined this issue by having participants
      complete a final individual recognition test following a recognition test in
      which the participants worked with a virtual confederate. The results suggest
      that responses from virtual confederates affect participants' performance in ways
      similar to actual confederates and that conforming to a virtual confederate's
      responses does appear to result in actual deficits in memory. More specifically,
      it impairs participants' ability to correctly recognise material presented
      earlier.

PMID- 15724912
TI  - The magic number.

PMID- 15724911
TI  - Memory for temporal context: effects of ageing, encoding instructions, and
      retrieval strategies.
AB  - Young and older adults were compared on a list discrimination task. In Experiment
      1, performance declined with ageing after incidental and intentional encoding of
      the temporal context. Moreover, there was no benefit for intentional encoding in
      either group. In Experiment 2, each list was associated with a different encoding
      context. There were age differences in performance when participants tried to
      retrieve the encoding context of the items as a cue for their list of occurrence,
      but not when participants evaluated temporal distance from the strength of the
      memory trace. This suggests that the age-related decrease in list discrimination
      could be at least partly due to a difficulty in inferring strategically the
      temporal context of the items from information encoded in the same time.

PMID- 15724913
TI  - The cold-pill crackdown.

PMID- 15724914
TI  - A snapshot of teen sex.

PMID- 15724915
TI  - Season of dry eyes.

PMID- 15724916
TI  - [Immune system and gastrointestinal diseases].

PMID- 15724917
TI  - [Psychovegetative aspects of mechanic failure of the cardiac muscle in an acute
      period of transmural myocardial infarction].
AB  - AIM: To study psychoemotional, typological personality characteristics and
      vegetative status of patients with mechanical complications of acute transmural
      myocardial infarction (MI). MATERIAL AND METHODS: 107 patients with acute
      transmural MI were divided into three groups depending on the kind of mechanical
      myocardial failure (MMF) or its absence. The control group consisted of 20
      healthy patients. The patients were examined for psychoemotional and typological
      features of personality and vegetative tone. RESULTS: Introverts were prevalent
      among MI patients with MMF. A psychological picture of the examinees was made.
      The study group patients displayed vegetative dysfunction syndrome. A cognitive
      component of high anxiety in patients with postinfarction MMF was specified.
      CONCLUSION: A cognitive component of anxiety in patients with acute transmural MI
      and MMF differs from that of patients with an uncomplicated course of the disease
      being hardly responsive to conventional therapy. Somatic component of anxiety in
      such patients manifests with vegetative dysfunction syndrome and demands
      prescription of beta-adrenoblockers as early as possible.

PMID- 15724918
TI  - [Assessment of myocardial viability and recovery of the left ventricular function
      in postmyocardial infarction patients].
AB  - AIM: To evaluate prognostic significance of myocardial viability (MV) depending
      on treatment policy in postmyocardial infarction (PMI) patients. MATERIAL AND
      METHODS: The study included 196 patients (172 males, 24 females, age 30-75, mean
      age 53 +/- 8.6 years). Standard stress dobutamine echocardiography was made 14 +/
      6 days (8-21 days) after macrofocal MI. Reperfusion therapy was made in 138
      (70%) patients. X-ray contrast coronary angiography was performed in all the
      patients as the criterion of the immediate effect of reperfusion was achievement
      of residual stenosis of MI-related coronary artery < 50%. Late after MI (18 +/- 7
      months after MI) a comparative analysis of the left ventricular function was made
      in three groups of patients depending on the clinical response to the treatment.
      MV criterion was based on a fall in the index of infarction zone wall movement
      (IZWM) under low-dose dobutamine stress test reflecting contractile reserve of
      the infarction zone (CR). Left ventricular function recovery was judged by a
      decrease in initial IZWM index 18 months later vs the initial IZWM 14 days later.
      Thus contractile reversibility of the infarction zone (CRIZ) was determined. LV
      function was also assessed by the index of left ventricular end diastolic volume
      (LVEDV), by the index of left ventricular end systolic volume (LVESV), left
      ventricular ejection fraction (LVEF). RESULTS: 18 months after MI, CRIZ was
      higher in group 1 (after effective reperfusion) and group 3 (after myocardial
      revascularization) compared to group 2 (medication only): 0.33 +/- 0.01, 0.39 +/-
      0.02 and 0.23 +/- 0.01, respectively. LVEDV and LVESV in group 1 and 3 diminished
      while LVEF increased. LVEDV in group 2 remained elevated though EF rose
      considerably. CONCLUSION: Recovery of LV contractile function depends much on
      reestablishment of adequate myocardial perfusion by reperfusion therapy or
      myocardial revascularization. Chronic myocardial hypoperfusion leads to LV
      remodeling. CRIZ proved a significant prognostic criterion of the IZWM index 18
      months after MI only in patients given effective reperfusion therapy.

PMID- 15724919
TI  - [Effects of exercise on markers of hemostatic activation in young survivors of
      myocardial infarction].
AB  - AIM: To study the effect of exercise on markers of endothelial impairment,
      platelet activation, thrombin formation, fibrinolysis in patients who survived
      myocardial infarction (MI) at young age. MATERIAL AND METHODS: The levels of
      fibrinogen (F), Willebrand factor (WF), beta-thromboglobulin (BTG), fragment 1+2
      of prothrombin activation (F 1+2), antigen of tissue plasminogen activator (TPA),
      D-dimer at rest as well as betaTG, F 1+2, WF, TPA antigen and its activity in
      treadmill test (TT) were compared in 25 patients younger than 35 years who
      survived Q-myocardial infarction (Q-MI) > 6 months before (group 1), 10 of whom
      had unaffected or little affected coronary arteries as shown by
      coronaroangiography (subgroup 1H) while 15 had stenosing coronary atherosclerosis
      (subgroup 1A); in 20 patients who had Q-MI at the age of 40-55 years (group 2);
      in 10 healthy patients under 35 years of age (group 3). RESULTS: Initial
      concentrations of F, F 1+2 and TPA antigen were significantly higher than in
      healthy subjects. F and TPA antigen were higher in subgroup 1A than in subgroup
      1H. D-dimer was higher in group 2 vs 1. TT raised concentration of BTG in all the
      groups, induced a stable trend of F 1+2 rise in patients of subgroup 1H (p =
      0.059), raised WF only in group 3, TPA antigen at peak stress in all the patients
      being in group 1 higher than in healthy controls and in subgroup 1A than in
      subgroup 1H. TPA antigen was more active at the peak stress in group 1 than in
      group 2 but the differences became insignificant in analyzing only patients who
      reached submaximal load by heart rate. CONCLUSION: Stenosing coronary
      atherosclerosis in patients after MI at young age is associated with high F and
      TPA levels. Elevated F 1+2 was registered at exercise test in young patients free
      of coronary obstruction. TPA levels were raised higher by exercise in patients
      with stenosing atherosclerosis of the coronary arteries. TPA activity induced by
      exercise depended more on exercise intensity than on the age of the patients.

PMID- 15724920
TI  - [A clinical course of coronary heart disease after pacemaker implantation and
      optimization of the pacing regime].
AB  - AIM: To study effects of pacemaker implantation on the course of coronary heart
      disease (CHD) with stable angina pectoris and choice of optimal regimen of
      pacing. MATERIAL AND METHODS: A total of 154 CHD patients with a pacemaker were
      examined. All the patients had angina of effort of functional class II-IV.
      RESULTS: The symptoms of the disease improved in 72 (46.8%) patients (group 1):
      the number of anginal attacks decreased, exercise tolerance increased, the dose
      of antianginal medicines went down. Pain attacks became more frequent, response
      to nitroglycerin changed in 30 (19.5%) patients of group 2. This was explained by
      1.5-2-fold enhancement of heart rate by pacemaker raising myocardial oxygen
      consumption and psychocardial syndrome. In 52 (33.8%) patients of group 3 anginal
      attacks characteristics did not change. CONCLUSION: To optimize coronary reserve,
      frequency of electroimpulses must be reprogrammed to adjust to a functional class
      of angina and chronic cardiac failure as well as pacing regime. In particular,
      low coronary reserve demands optimal frequency of 55-65 imp/min while congenital
      cardiac failure--75-85 imp/min.

PMID- 15724921
TI  - [The role of hypersympathycotony in development of arterial hypertension in
      patients with metabolic syndrome: potential of pathogenetically sound therapy].
AB  - AIM: To assess hypotensive efficacy and metabolic neutrality of moxonidine
      (physiotenz)--a selective agonist of imidasoline receptors--in patients with mild
      and moderate arterial hypertension (AH) associated with diabetes mellitus (DM)
      type 2. MATERIAL AND METHODS: Follow-up and treatment were conducted in 30
      hypertensive diabetics (mean age 52.43 +/- 4.65 years). Mean duration of DM and
      AH was 4.77 +/- 2.69 and 6.93 +/- 2.98 years, respectively. The study was made of
      lipid exchange, glycemia, levels of glycosylated hemoglobin (GH), fasting and
      postprandial immunoreactive insulin. Hypotensive efficacy was examined by 24-h
      monitoring of arterial pressure after 16 weeks of therapy. RESULTS: Mean 24-h
      systolic arterial pressure fell by 8.02%, diastolic arterial pressure--by 6.47%.
      The drug had a good effect on a 24-h profile of arterial pressure: a significant
      decrease of day and night pressure load index, lowering of initially high 24-h
      variability of systolic and diastolic arterial pressure, normalization of two
      phase profile of arterial pressure. Carbohydrate metabolism improved also: GH,
      glycemia, immunoreactive insulin decreased. There was a significant trend to a
      change in qualitative composition of blood lipid--a decrease in lipoproteins
      atherogenic fractions and a rise in HDLP. CONCLUSION: Physiotens is a highly
      effective hypotensive drug for use in mild and moderate AH in DM of type 2.

PMID- 15724922
TI  - [Practical prevention and treatment of cardiovascular diseases in patients with
      diabetes mellitus type 2 in an endocrinological department].
AB  - AIM: To analyse retrospectively quality of medical correction of modified risk
      factors (RF) and treatment of cardiovascular diseases (CVD) in patients with
      diabetes mellitus type (DM) 2 admitted to specialized endocrinological
      departments. MATERIAL AND METHODS: Analysis of medication policy of CVD RF was
      made retrospectively for 250 patients treated in endocrinological departments of
      Moscow hospital in 2003. RESULTS: Arterial hypertension, coronary heart disease
      were diagnosed in 93.2 and 87.2% examinees. History of myocardial infarction and
      brain stroke was in 8.4 and 6% patients. Statins were prescribed in 2.4% cases.
      Examination for dyslipidemia was not satisfactory. ACE inhibitors were prescribed
      in 71.2% patients. Aspirin was prescribed (18%) primarily by the cardiologist.
      CONCLUSION: Quality of medical prophylaxis of CVD RF in DM type 2 patients in the
      departments does not satisfy modern clinical recommendations.

PMID- 15724923
TI  - [Carotid atherosclerosis detectability in patients with coronary heart disease
      and arterial hypertension].
AB  - AIM: To assess detectability of carotid atherosclerosis in patients with coronary
      heart disease (CHD) and arterial hypertension (AH) by the data of ultrasonic
      screening, to study location and detectability of atherosclerotic lesion of
      common carotid arteries, internal carotid arteries, external carotid arteries in
      correlation with basic disease. MATERIAL AND METHODS: Ultrasonic screening of
      brachyocephalic arteries was made in 469 patients: with CHD (n = 239), AH (n =
      230) including patients with concomitant postinfarction cardiosclerosis (PICS)
      and moderate chronic cerebrovascular failure (CCVF). RESULTS: Ultrasonic
      angiography detected atherosclerotic carotid artery lesion in patients with CHD
      and PICS (81.6%) or CCVF (76.9%) or angina pectoris (64.2%). In hypertension
      subjects carotid artery atherosclerosis was encountered in 28.1%. CONCLUSION: It
      is justified to make ultrasonography of carotid arteries in all patients with CHD
      and AH irrespective of age, gender, underlying clinical diagnosis.

PMID- 15724924
TI  - [Vasoregulating activity of the endothelium and pulmonary hypertension].
AB  - AIM: To examine vasoregulating endothelial activity in patients with bronchial
      asthma (BA) with pulmonary hypertension (PH) and free of PH. MATERIAL AND
      METHODS: A total of 62 BA patients aged between 19 and 52 entered the trial. They
      were divided into two groups: 44 with PH and 18 free of it. The control group
      consisted of 35 healthy subjects. Vasoregulating activity of the vascular wall
      was studied by tests with reactive hyperemia (endothelium-dependent dilation) and
      0.05 mg nitroglycerin (endothelium-dependent dilation). RESULTS: It was found
      that BA patients with PH have a dilated brachial artery, abnormal endothelium
      dependent vasodilation of the brachial artery. The artery is low sensitive to
      shift tension. These changes in functional activity of brachial artery
      endothelium in BA patients with PH are associated with impaired pulmonary
      hemodynamics, right ventricular diastolic function.

PMID- 15724925
TI  - [Echocardiography--prognosis of the course of infectious endocarditis and long
      term survival in this disease].
AB  - AIM: To determine prognostic opportunities of echocardiography (ECG) in
      infectious endocarditis (IE) basing on the assessment of microbial vegetations
      size and degree of valvular failure. MATERIAL AND METHODS: Of 114 patients with
      definite IE (72 male, 42 female), 90 ones had primary and 24 secondary
      endocarditis. The prospective study included all the survivors in the IE active
      stage--78 patients. RESULTS: Vegetations > 1 cm in size were detected in 50.8%
      patients, < 1 cm--in 49.2%. Hospital lethality in vegetations > 1 cm and < 1 cm
      was 25.8 and 16.1%, respectively. Thromboembolism rate was 81 and 64.2%,
      respectively. One-year survival was 78.7 and 71.4%, two-year survival 66.5 and
      61.7%, three-year survival 66.5 and 49.4%, five-year survival--51.7 and 32.9% in
      vegetations < 1 cm and > 1 cm, respectively. Valvular regurgitation of the first
      degree was in 17.5%, of the second degree--in 41.9%, third-fourth degree--in
      36.6% patients. Hospital lethality in mitral valve failure was 32.1%, in aortic
      and tricuspid failure--17.8 and 11.4%, respectively. CONCLUSION: EchoCG was most
      effective for predicting thromboembolism and cardiac failure. Valvular
      regurgitation of the third-fourth degree significantly correlates with severe
      cardiac failure. ECG is less informative for predicting hospital lethality.

PMID- 15724926
TI  - [Clinical response to Ginkor-Fort in the treatment of chronic venous
      insufficiency in varicosity].
AB  - AIM: Assessment of clinical efficacy and tolerance of the drug Ginkor-Fort in
      patients with chronic venous insufficiency (CVI) in varicosity in compensation
      stage. MATERIAL AND METHODS: Thirty patients with compensated CVI free of trophic
      ulcers of the legs received Ginkor-Fort 1 capsule twice a day for one month. The
      efficacy of the drug was assessed by subjective appraisal of the patients,
      physical examination data and results of repeated measurements of the leg at the
      malleolus level. RESULTS: A course of Ginkor Fort produced a considerable
      improvement in 27 (90%) patients. Improvement of the condition occurred in 3
      (10%) patients. Side effects were absent, the treatment was well tolerated. All
      the patients completed a one-month Ginkor-Fort course. CONCLUSION: Ginkor Fort is
      a highly effective and safe phlebotonic drug. Its high anti-inflammatory,
      anesthetic, lymphodraining and phlebotonic effects noticeably and rapidly raise
      life quality of patients with varicosity.

PMID- 15724927
TI  - [Bronchoobstructive syndrome in bronchoectasias].
AB  - AIM: To specify mechanisms of bronchial obstruction in bronchoectasia (BE).
      MATERIAL AND METHODS: Clinical, x-ray, bronchological and spirographic
      examinations with broncholytic test were made in 26 BE patients aged 16-66 years
      (14 males, 12 females). The membrane-receptor complex of erythrocytes was based
      on the effect of adrenoantagonist propranolol on osmotic erythrocytic resistance
      (obsidan test) and effect of adrenoagonist adrenalin on dynamics of ESR. RESULTS:
      Allergological anamnesis was detected in 69% of BE patients, hereditary
      allergological anamnesis--in 22%, membrane-receptor changes characteristic for
      atopic condition by obsidan test--in 46%, fractional erythrocytic sedimentation
      with adrenalin--in 42%. Bronchoobstruction syndrome occurred in 37% cases with
      mean values FEV1 46 +/- 6.2%, MSV50 17.4 +/- 3%, MSV75 14.4 +/- 0.9%. The
      broncholytic test detected a mean increment of FEV1 by 12.2 +/- 3.1%. Latent
      bronchospasm was revealed in 33% patients with BE. CONCLUSION: The correlation
      analysis suggests that among mechanisms of bronchial obstruction in
      bronchoectasia, bronchospasm is of great importance especially in allergological
      anamnesis pathogenesis of which involves disorders of membrane-receptor complex.

PMID- 15724928
TI  - [Phenomenon of hyperexpression of ribosomic cistrons in bone marrow hemopoietic
      elements in bronchial asthma].
AB  - AIM: To study expression of ribosomic cistrons (RC) of bone marrow hemopoietic
      elements (BMHE) in bronchial asthma (BA). MATERIAL AND METHODS: A total of 37
      bronchial asthma (BA) patients were examined. Of them, 20 ones had allergic BA
      (ABA) and 10--nonallergic BA (NABA). Seven patients received systemic
      glucocorticoid hormones (SGH). Control included cells of bone marrow from 7
      healthy donors. Transcription and maturation of pre-rRNA in BMHE were analysed
      using bone marrow samples obtained during the sternal puncture (a modified method
      of Howell and Black). RESULTS: RC activity was high. It depended on BA variant
      and the disease phase. In ABA high RC activity persisted in remission. GCH
      suppress RC activity rise. The maximal effect of GCH suppressive action was seen
      in myeloid lineage, minimal--in erythroid one. The effect is absent in more
      mature erythroid cells and bone marrow lymphocytes. CONCLUSION: The phenomenon of
      RC activity rise in myeloid, erythroid and lymphoid lineages of the bone marrow
      of BA patients may reflect contribution of the bone marrow to formation of BA
      pathogenesis.

PMID- 15724929
TI  - [Endothelium and platelets in pregnant women with chronic glomerulonephritis and
      therapeutic efficacy of acetylsalicylic acid and dipiridamol].
AB  - AIM: To estimate platelet and endothelial condition in pregnant women with
      chronic glomerulonephritis (CGN), prognostic value of these changes and efficacy
      of acetylsalicylic acid (ASA) and dipiridamol in prevention of unfavourable
      outcomes of pregnancy in CGN. MATERIAL AND METHODS: The examination covered 74
      CGN pregnant patients, 14 non-pregnant CGN patients, 11 pregnant women with
      preeclampsia, 19 healthy pregnant women. The levels of fibronectin, endothelin
      1,2, 6-keto-PGF1a, thromboxane B2 (TxB2) secretory beta-thromboglobulin in the
      blood, activity of intrathrombocytic lactate dehydrogenase (LHG), platelet
      aggregation. ASA (125 mg/day) was given to 33 CGN pregnant women in combination
      with dipiridamol (150-225 mg/day). Control group consisted of 32 CGN pregnant
      women. RESULTS: Content of fibronectin, endothelin, TxB2 and beta-thromboglobulin
      in blood plasm, aggregation with ADP in CGN pregnant women were higher than in
      healthy pregnant women and nonpregnant CGN patients. Plasmic 6-keto-PGF1a was
      low. Preeclampsia was accompanied with elevated fibronectin, TxB2 and beta
      thromboglobulin, hyperactive LDH. Platelet aggregation was suppressed. Blood beta
      thromboglobulin directly correlated with systolic and diastolic arterial
      pressure, 24-h proteinuria and blood creatinine. Reverse Correlation was seen in
      blood beta-thromboglobulin with albuminemia, glomerular filtration rate, body
      mass of the newborn and term of labor. A direct correlation was found between the
      activity of intrathrombocytic LDH and systolic and diastolic arterial pressure, a
      weak reverse correlation--between platelet count in capillary blood and systolic
      pressure, platelet aggregation with ADP and terms of labor. Of the highest
      prognostic value were the level of beta-thromboglobulin and fibronectin, the
      activity of intrathrombocytic LDH and platelet aggregation in response to ADP.
      ASA and dipiridamol reduced the risk of fetal retardation and fetal loss.
      CONCLUSION: Pregnant women with CGN have endothelial-thrombocytic dysfunction
      because of unidirectional influence of both CGN and pregnancy. We think that
      endothelial-platelet dysfunction connects renal impairment and placental failure
      in pregnant women with CGN deteriorating a gestational CGN and pregnancy
      complications. Correction of endothelial-platelet state with ASA and dipiridamol
      is effective in prevention of fetal retardation and fetal loss in pregnant women
      with CGN.

PMID- 15724930
TI  - [Antibodies to cyclic citrullinized peptide in rheumatoid arthritis].
AB  - AIM: To estimate a diagnostic value of antibodies to cyclic citrullinized peptide
      (CCP) in rheumatoid arthritis (RA). MATERIAL AND METHODS: The study was made of
      85 RA patients. Of them, 48 patients had early RA, i.e. of 8 month and less
      duration. The control group consisted of 35 patients with non-differentiated
      arthritis (NDA) and 8 healthy donors. Concentrations of CCP antibodies,
      rheumatoid factor (RF) IgM and RF IgA were measured with enzyme immunoassay
      (EIA). RESULTS: The level of CCP antibodies in RA patients (76.3 +/- 43.8; median
      100.0 U/ml) was significantly higher than in NDA patients (25.1 +/- 43.9; median
      0.8 U/ml; p < 0.05) or in donors (0.38 +/- 0.36; median 0.2 U/ml; p < 0.05). A
      correlation was found between the CCP antibodies level and that of RF IgM (chi2 =
      15.4; p = 0.001) and RF IgA (chi2 = 10.3; p = 0.001). Sensitivity (82%) and
      specificity (90%) of CCP antibodies in RA diagnosis was higher than these
      parameters for RF IgM and IgA (78%, 86% and 72%, 83%, respectively). Simultaneous
      tests for CCP antibodies, RF IgM and RF IgA led to a 93% specificity. CCP
      antibodies were detected in 50% patients seronegative by RF IgM and in 62%
      patients seronegative by IgA. Detection of CCP antibodies was closely associated
      with early RA (chi2 = 30.8; p = 0.0001). CONCLUSION: The EIA for CCP antibodies
      is a sensitive and specific serological test for early RA diagnosis.

PMID- 15724931
TI  - [Clinical biological features of mixed myeloid diseases].
AB  - AIM: To characterize patients with mixed myeloid neoplasias with proliferation of
      neutrophils, platelets and eosinophils. MATERIAL AND METHODS: Examination and
      treatment results were analysed for patients with atypical myeloid leukemia (n =
      4), myelodysplastic syndrome (MDS, n = 1) and thrombocytosis, MDS and
      eosinophilia (n = 1). The examination included morphological, histological,
      cytogenetic and molecular tests. RESULTS: One patient with atypical chronic
      myeloid leukemia was prior diagnosed to have primarily MDS with a typical
      aberration of chromosome 5. Two other patients had an initial morphological
      picture of resistant anemia with blast excess, signs of myeloproliferation and
      extramedullary hemopoiesis. One and two months after the first examination they
      received transfusions of erythrocytic mass. Just then they were found to have
      splenomegaly and leukocytosis due to proliferating and maturating forms of
      neutrophils. The course of the disease in patients with MDS, thrombocytosis and
      normal karyotype and in patients with MDS, eosinophilia and combined chromosomal
      breaks including translocation (3;12)(q21;p13) was characterized by resistance to
      standard programs of polychemotherapy and transformation into acute myeloblastic
      leukemia. CONCLUSION: In some cases atypical CML is a stage of a natural course
      of MDS. Some MDS variants with eosinophilia and thrombocytosis should be referred
      to the group of mixed myeloid neoplasias.

PMID- 15724933
TI  - [Neurohumoral aspects of energy metabolism regulation].

PMID- 15724932
TI  - [A case of effective use of alemtuzumab in a male patient with T-cell lymphoma].

PMID- 15724934
TI  - [Efficacy and tolerance of stepwise therapy with movalis in rheumatic diseases].

PMID- 15724935
TI  - [Chronic obstructive pulmonary disease in combination with cardiovascular
      diseases: treatment with inhalatory cholinolytic drugs].

PMID- 15724936
TI  - [Current pathogenetic model of rheumatoid arthritis and its role in clinical
      practice].

PMID- 15724937
TI  - [Carvedilol (dilatrend) treatment in cardiac failure].

PMID- 15724938
TI  - [An adverse effect of amiodaron on the skin].

PMID- 15724939
TI  - [Low-molecular heparins in the treatment of non-ST elevation acute coronary
      syndrome].

PMID- 15724940
TI  - [Cardiovascular status in patients with hypothyroidosis in the elderly].

PMID- 15724941
TI  - [Rating system in medical education].

PMID- 15724942
TI  - Pathophysiology of bone cancer pain.
AB  - The most common cancers, such as those affecting the breast, prostate, and lung
      have a strong predilection to metastasize to bone. Bone metastasis frequently
      results in pain, pathologic fractures, hypercalcemia, and spinal cord
      compression. Pain can have a devastating effect on the quality of life in
      advanced cancer patients and is a serious complication of cancer. Although
      significant advances are being made in cancer treatment and diagnosis, the basic
      neurobiology of bone cancer pain is poorly understood. New insights into the
      mechanisms that induce cancer pain now are coming from animal models. Chemicals
      derived from tumor cells, inflammatory cells, and cells derived from bone appear
      to be involved simultaneously in driving this frequently difficult-to-control
      pain state. Understanding the mechanisms involved in the pathophysiology of bone
      cancer pain will improve both our ability to provide mechanism-based therapies
      and the quality of life of cancer patients.

PMID- 15724943
TI  - From the bench to an evolving controversy.

PMID- 15724944
TI  - Are inflammatory cytokines the common link between cancer-associated cachexia and
      depression?
AB  - The prevalence of depression among patients diagnosed with cancer is higher than
      among the general medical population and is associated with faster tumor
      progression and shortened survival time. Cancer-related depression often occurs
      in association with anorexia and cachexia, although until recently the
      relationship between these conditions has not been well understood. Cachexia is
      associated with poorer quality of life and survival outcomes and is theeventual
      cause of death in approximately 30% of all patients with cancer. Recent evidence
      has linked elevated levels of inflammatory cytokines with both depression and
      cachexia, and experiments have shown that introducing cytokines induces
      depression and cachectic symptoms in both humans and rodents, suggesting that
      there may be a common etiology at the molecular level. Therapeutic agents
      targeting specific cytokine molecules, such as interleukin-6 or tumor necrosis
      factor-alpha, are currently being evaluated for their potential to simultaneously
      treat both depression and cachexia pharmacologically. This review summarizes the
      available data suggesting a dual role for cytokines in the development of cancer
      related depression and cachexia and describes how biologic therapies targeting
      specific cytokines may improve outcomes beyond depression and cachexia, such as
      survival and quality of life.

PMID- 15724945
TI  - Entering a new era in the management of tumor-associated involution.

PMID- 15724946
TI  - Cytokines, cancer and depression: connecting the dots.

PMID- 15724947
TI  - Principles of ostomy management in the oncology patient.
AB  - Fecal and urinary diversions are fairly common among patients diagnosed with
      abdominal and pelvic malignancies who have undergone removal of the bladder or
      rectum or who have suffered from obstruction caused by tumor invasion or
      radiation damage. Effective ostomy management is important in palliative care and
      involves establishment of an effective pouching system, attention to diversion
      specific alterations in dietary and fluid intake, and management of peristomal
      and stomal complications. Management of colostomy must include measures to
      prevent or manage constipation, management of ileostomy must include strategies
      for maintenance of fluid-electrolyte balance and prevention of food blockage, and
      management of urinary diversion must include options to be used at night and a
      focus on consistent adequate fluid intake. Common peristomal and stomal
      complications may necessitate use of barrier products, convex pouching systems to
      compensate for retraction, and/or binders. Surgery may be needed if incarcerated
      hernias, persistent prolapse, or stenosis severe enough to interfere with
      function occur.

PMID- 15724948
TI  - Ostomy care: the added considerations for cancer patients.

PMID- 15724949
TI  - Dealing with ostomies: good care, good devices, good quality of life.

PMID- 15724950
TI  - A simplified premedication schedule for 1-hour paclitaxel administration.
AB  - Many investigations have focused on an optimal dosing schedule for paclitaxel
      since its regulatory approval. Paclitaxel is generally administered at a dose of
      175 mg/m2 IV over 3 hours or 135-175 mg/m2 IV over 24 hours, every 3 weeks. The
      purpose of this study was to simplify the administration of paclitaxel to make it
      suitable and practical in the outpatient setting. Using this rationale, the
      duration of administration was decreased to 1 hour, with a minimized
      premedication regimen. Fifty-two patients scheduled to receive paclitaxel-based
      chemotherapy were entered into the study. Tumor types included non-small cell
      lung cancer, small cell lung cancer, breast cancer, head and neck cancer, and
      ovarian cancer. Twelve patients received paclitaxel 175 mg/m2 IV, and the
      remaining 40 patients received paclitaxel 225 mg/m2 IV. Premedication consisted
      of IV dexamethasone 20 mg over 5-10 minutes, given 30-60 minutes before infusion
      of paclitaxel,followed by IV dimethindene maleate 4 mg and IV ranitidine 50 mg
      over 30 minutes. Paclitaxel always was administered before other chemotherapeutic
      agents. Hypersensitivity reactions were recorded in 4 patients (7.7%) and were
      not influenced by age, gender, disease, dose schedule, or number of cycles of
      therapy; no serious hypersensitivity reactions were observed. The present study
      supports the efficacy and safety of a short premedication schedule; with further
      study, this schedule might become a standard premedication protocol prior to
      paclitaxel administration.

PMID- 15724951
TI  - Managing pain in patients with aberrant drug-taking behaviors.

PMID- 15724952
TI  - [Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic
      syndrome].
AB  - The metabolic syndrome has several similarities with Cushing's syndrome (impaired
      glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that
      abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may
      have a link with the metabolic syndrome. Several studies suggested an association
      between the clinical signs of the metabolic syndrome and the increased
      hypothalamic-pituitary-adrenal axis activity based on increased cortisol
      concentration at 09.00 a.m. and increased cortisol response to corticotropin.
      According to the Barker hypothesis the fetal malnutrition could determine adult
      cardiovascular diseases (coronary heart disease, hypertension), some endocrine
      and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The
      suggested mechanism of the phenomenon is that the suboptimal fetal nutrition
      results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase
      (converts biological inactive cortisone to cortisol and vice versa) is an
      important enzyme in cortisol metabolism. The increased expression of 11beta
      hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity
      and impaired glucose tolerance. The hypothesis that increased corticotropin
      releasing hormone production drives the overactive hypothalamo-pituitary-adrenal
      axis was not proven. Further investigations are needed to identify additional
      pathogenetic factors and to find new therapeutic possibilities.

PMID- 15724953
TI  - [Primary treatment of early stage Hodgkin's disease].
AB  - Until the beginning of the 1990s, early stage Hodgkin's disease had been treated
      by (involved field) radiotherapy in most cases. Since the mid-1990s, by revealing
      a range of prognostic factors and late complications of radiotherapy, the
      treatment protocol has been modified. The use of combined modality therapy
      (programmed combined use of chemo- and radiotherapy) has gained ground. At
      present, in early stage Hodgkin's disease, 2-6 cycles ABVD followed by decreased
      dose involved field irradiation is considered to be the standard treatment. The
      number of chemotherapy cycles depends on the prognostic factors and reaction
      time. In cases of early stage nodular lymphocyte predominance with good
      prognosis, only involved field irradiation therapy is used.

PMID- 15724954
TI  - [Vascular effects of physical activity].
AB  - Regular physical activity decelerates the aging processes of the arterial wall
      and of the endothelial functions, which is denoted with slackening of the
      propagation velocity of the pulse wave or by echo checking of the postischemic
      dilatation of the limb vessels. Of the factors evoking, organizing and executing
      the dilation and constriction of the arteries, the role of the endothelial
      nitrogen oxide, of the angiogenesis, and of the balance of the hemostasis seems
      to be the most important and best recognized. Even few months of training program
      improves the endothelial functions if the amount and the intensity suits to the
      recommended in cardiovascular diseases. Physical training is a very effective
      course for prevention and rehabilitation in various conditions incidental to
      endothelial dysfunction. Damaged endothelial function predisposes to local
      thrombotic events. Thrombogenic prevalence can be normalized by physical activity
      at many steps of the hemostasis: activated fibrinolysis, more favorable blood
      viscosity, lower plasminogen activator inhibitor (PAI-1) level, decreased
      platelet activity.

PMID- 15724955
TI  - [Surgical management of preterm infants and low birth weight neonates with
      congenital heart disease].
AB  - Nowadays, due to the development of cardiac surgery, pediatric cardiology and
      anesthesia, almost every congenital heart disease can be corrected totally or
      partially. The increasing number of surgical corrections will lead to better life
      quality. The surgical mortality has decreased significantly, even in the most
      complex cases. Only few cases can not be treated surgically. The aim of this
      study was to examine these positive changes, what they mean in the treatment of
      premature babies with congenital heart disease. These patients are endangered
      because of their age as well, they require special treatment and the surgical
      treatment has always meant high risk, urgent interventions. PATIENTS: between 01.
      01. 1975. and 31. 12. 2003. 447 premature babies were operated on. The patients
      were divided into 3 subgroups by their weight: I: 470-1500 gr. - 19 patients, II:
      1500-2000 gr. - 93 pts., IIl: > 2000 gr. - 335 pts. There were 69 corrective
      surgical procedures performed mainly after 1998. RESULTS: Overall early
      mortality: 81 patients (18.1%). Detailed mortality: group I.: 0%, group 11: 23
      (24.7%), group III.: 58 (17.3%). The early mortality reduced from 21.6% to 6.3%
      (closed procedure), and 27.7% to 10.8% (ECC operation). The successful operations
      in the smallest weight groups were as follows: On ECC: Total Anomalous Pulmonary
      Venous Return (1600 g), Transposition of the Great Arteries--Arterial Switch
      (1800 g), Ventricular Septal Defect (1800 g), Aortopulmonary fenestration (2000
      g), Hypoplastic Left Heart Syndrome-Norwood procedure (2200), AV septal defect
      (2300 g), Interrupted aortic arch + Ventricular Septal Defect (2300 g), Truncus
      arteriosus (2500 g). Without ECC: Coarctation of the aorta (930 g), Patent Ductus
      Arteriosus (470 g). CONCLUSION: Nowadays the possibilities and the chances of the
      corrective procedures of congenital heart diseases in those patients with
      bodyweight of over 2000 g and in those that are mature babies are the same. In
      those patients with bodyweight 1500-2000 g procedures without ECC had good
      results, on-pump procedures had higher mortality rate, but the long-term results
      were acceptable. At the moment only procedures without ECC are performed on
      babies with weight under 1500 g--but with higher risk. Our effort is to perform
      ECC operations in patients with bodyweight less than 1500 g.

PMID- 15724956
TI  - [Treatment results with ALL-BFM-95 protocol in children with acute lymphoblastic
      leukemia in Hungary].
AB  - BACKGROUND: In Hungary children (from 1 to 18 years of age) with de novo acute
      lymphoblastic leukemia were treated from January 1996 to October 2002, according
      to protocol ALL-BFM-95. AIM: The aim of this study was to evaluate the experience
      with this protocol, the treatment results according to the risk groups and to
      compare the Hungarian data with the international results. METHODS: Patients were
      stratified into 3 risk groups, based on initial white blood cell count, age,
      immunology, cytogenetics and response to treatment: standard, medium and high
      risk group. RESULTS: Three hundred sixty eight children entered the study (male
      female ratio was 1.27:1, median age 6 years and 4 months). 110 (29.9%) children
      were in the standard, 210 (57.1%) in the medium and 48 (13%) in the high risk
      group. Duration of the chemotherapy was 2 years, except of the boys in the
      standard risk group, their maintenance therapy was 1 year longer. The overall
      complete remission rate was 93.2%. 20 (5.4%) children died in induction and 5
      (1.4%) were non-responders. The 5-year overall survival for all patients was
      78.5%, in the standard risk group 93.2%, in the medium risk group 78.4% and in
      the high risk group 44.5% with a minimum follow up of 1.19 years and median
      follow up of 4.85 years. From the 368 patients 272 (73.9%) are still in their
      first complete clinical remission and other 18 children are alive after relapse.
      In 14.7% of the patients relapse was diagnosed; the most common site was the bone
      marrow. In one patient second malignancy occurred. The 5-year event free survival
      for all patients was 72.6%, in the standard risk group 87.6%, in the medium risk
      group 72.1% and in the high risk group 39.9%. CONCLUSION: The treatment outcome
      of children with acute lymphoblastic leukemia improved remarkably over the last
      decades. 78% of children suffering from acute lymphoblastic leukemia could be
      cured with the ALL-BFM-95 protocol. The Hungarian results are comparable to those
      achieved by other leukaemia study groups in the world regarding the ALL-BFM-95
      protocol.

PMID- 15724957
TI  - [Treatment of superficial thrombophlebitis].

PMID- 15724958
TI  - [Gabor Lusztig (1925-1991)].

PMID- 15724959
TI  - [Historical survey and legal analysis of the concept of medical malpractice].

PMID- 15724960
TI  - The eighth day of discovery: molecular biology comes to chemical ecology.

PMID- 15724961
TI  - Functional genomics and insect chemical ecology.
AB  - High-throughput molecular techniques (i.e., genomics) are now beginning to make
      their way into chemical ecology research. Pioneering functional genomics studies
      have made significant contributions to our understanding of insect pheromone
      production, reception, behavior, and insect-plant interactions. Much of this
      research involves nonmodel organisms, including the honey bee, silkworm, and bark
      beetles, underscoring that researchers need not be restricted to traditional
      model organisms for high-throughput research. Furthermore, the technology can
      reveal physiological interactions that might otherwise be missed by more
      traditional molecular approaches. Functional genomics should become more widely
      used as researchers appreciate the wealth of information this potent approach can
      supply. This review concentrates on a summary of available technologies for
      functional genomics as they may be applied by chemical ecologists studying
      insects. Allied technologies (proteomics and metabolomics) are introduced briefly
      toward the end in the context of future applications.

PMID- 15724962
TI  - Insect olfactory receptors: contributions of molecular biology to chemical
      ecology.
AB  - Our understanding of the molecular basis of chemical signal recognition in
      insects has been greatly expanded by the recent discovery of olfactory receptors
      (Ors). Since the discovery of the complete repertoire of Drosophila melanogaster
      Ors, candidate Ors have been identified from at least 12 insect species from four
      orders (Coleoptera, Lepidoptera, Diptera, and Hymenoptera), including species of
      economic or medical importance. Although all Ors share the same G-protein coupled
      receptor structure with seven transmembrane domains, they present poor sequence
      homologies within and between species, and have been identified mainly through
      genomic data analyses. To date, D. melanogaster remains the only insect species
      where Ors have been extensively studied, from expression pattern establishment to
      functional investigations. These studies have confirmed several observations made
      in vertebrates: one Or type is selectively expressed in a subtype of olfactory
      receptor neurons, and one olfactory neuron expresses only one type of Or. In
      addition, all olfactory neurons expressing one Or type converge to the same
      glomerulus in the antennal lobe. The olfactory mechanism, thus, appears to be
      conserved between insects and vertebrates. Although Or functional studies are in
      their initial stages in insects (mainly Drosophila), insects appear to be good
      models to establish fundamental concepts of olfaction with the development of
      powerful genetic, imaging, and behavioral tools. This new field of study will
      greatly contribute to the understanding of insect chemical communication
      mechanisms, particularly with agricultural pests and disease vectors, and could
      result in future strategies to reduce their negative effects.

PMID- 15724963
TI  - Genomic hardwiring and phenotypic plasticity of terpenoid-based defenses in
      conifers.
AB  - Over evolutionary history, conifers have faced a myriad of threats from phloem-
      and xylem-feeding insects, defoliating insects, and fungal pathogens. Among the
      trees' defenses, terpenoids appear to play a major role by harming, disabling,
      deterring, repelling, or otherwise reducing the fitness of potential invaders.
      Each of the three classes of terpenoids in conifers, monoterpenes,
      sesquiterpenes, and diterpenes, are composed of a large number of representative
      compounds. In most cases, the presence of a particular terpenoid compound in the
      oleoresin or volatile emissions from a specific conifer can be accounted for by
      the expression of one of many committed terpene synthase (TPS) genes. However,
      while each TPS may produce one or a few major products, many produce a variety of
      minor products with relatively constant component ratios in the product blends.
      TPS genes exist in conifers in large and functionally diverse, yet monophyletic,
      gene families. Within these gene families, new biochemical functions of TPS
      appear to have evolved by gene duplication and changes in the amino acid sequence
      of the enzyme's active site. In addition, TPS genes may be differentially
      expressed prior to, during, and following attack by insects or pathogens. Thus,
      while the production of any particular terpenoid is hardwired into a conifer's
      genome, these trees have the capacity to change the mixture of terpenoids in
      oleoresin secretions and volatile emissions. Anatomical changes may also
      accompany induced terpenoid production, supplementing the plasticity of the
      molecular and biochemical events.

PMID- 15724964
TI  - Gene-for-gene disease resistance: bridging insect pest and pathogen defense.
AB  - Active plant defense, also known as gene-for-gene resistance, is triggered when a
      plant resistance (R) gene recognizes the intrusion of a specific insect pest or
      pathogen. Activation of plant defense includes an array of physiological and
      transcriptional reprogramming. During the past decade, a large number of plant R
      genes that confer resistance to diverse group of pathogens have been cloned from
      a number of plant species. Based on predicted protein structures, these genes are
      classified into a small number of groups, indicating that structurally related R
      genes recognize phylogenetically distinct pathogens. An extreme example is the
      tomato Mi-1 gene, which confers resistance to potato aphid (Macrosiphum
      euphorbiae), whitefly (Bemisia tabaci), and root-knot nematodes (Meloidogyne
      spp.). While Mi-1 remains the only cloned insect R gene, there is evidence that
      gene-for-gene type of plant defense against piercing-sucking insects exists in a
      number of plant species.

PMID- 15724965
TI  - Characterization of a salivary lysozyme in larval Helicoverpa zea.
AB  - The cDNA sequence of a salivary lysozyme in Helicoverpa zea (Lepidoptera:
      Noctuidae) was determined. The full-length cDNA is 1,032 bp, and it encodes a
      protein of 142 amino acids. This lysozyme has 90% identity with Heliothis
      virescens lysozyme and 76% identity with Manduca sexta lysozyme. There is a
      signal peptide of 20 amino acids at the N-terminus. The mature protein is about
      14.4 kDa without the signal peptide. The pI value is greater than 9.5 as
      determined by isoelectric focusing. From genomic DNA, two introns and three exons
      were within the open reading frame (ORF). Southern blot analysis indicated that
      it is a single-copy gene. A time-course study revealed that the H. zea lysozyme
      gene was differentially expressed in the labial glands during the development of
      fifth-instar larvae, with the peak level of lysozyme mRNA being detected on day
      1. Dot blot analysis showed different levels of H. zea lysozyme expression when
      the caterpillars fed on different plants. Further, the H. zea lysozyme could be
      detected with antibodies raised against the M. sexta lysozyme, and it was one of
      the most abundant secreted proteins in saliva collected directly from the
      caterpillar's spinneret. The potential role of the lysozyme on host plants in
      mediating susceptibility to bacterial disease is discussed in the context of
      tritrophic interactions.

PMID- 15724966
TI  - Juvenile hormone regulates de novo isoprenoid aggregation pheromone biosynthesis
      in pine bark beetles, Ips spp., through transcriptional control of HMG-CoA
      reductase.
AB  - Evidence is presented for transcriptional regulation of de novo pheromone
      biosynthesis in Ips spp. bark beetles, but the comparative biochemical and
      molecular approach reveals a dichotomy between species in the pini and
      grandicollis subgeneric groups. Radiotracer studies with 14C-acetate demonstrate
      that feeding on host phloem stimulates biosynthesis in males of three Ips spp.
      However, treatment with juvenile hormone III (JH III) stimulates biosynthesis
      only in Ips pini. Thus, two species in the grandicollis subgeneric group (I.
      grandicollis and I. paraconfusus) appear to have a different mode of regulation
      related to JH III than does I. pini. Between 16 and 20 hr after feeding has
      commenced, pheromone production, as measured by accumulation in abdominal tissue,
      is stimulated about 150- (I. pini) and 350-times (I. paraconfusus) above the
      control level of 1-10 ng/male measured at 0 hr. Treatment with JH III results in
      accumulation in I. pini that is 3-4 times more than in phloem-fed males, whereas
      the identical treatment results in only weak accumulation in I. paraconfusus (45
      times less than phloem-fed males). Comparative studies of gene expression and
      enzyme activity related to biosynthesis also support different modes of JH III
      related regulation in I. pini and I. paraconfusus. In males of both species,
      feeding on host phloem results in increased transcript abundance and increased
      activity for the key de novo isoprenoid pathway enzyme 3-hydroxy-3-methylglutaryl
      CoA reductase (HMG-R). However, while JH III treatment results in comparable
      maximal increases in HMG-R transcript levels in both species (similar to
      feeding), the activity of HMG-R in crude extracts from JH III-treated male I.
      paraconfusus is low in comparison with male I. pini. Hypothetical explanations
      for the interspecific dichotomy in the regulation of pheromone biosynthesis
      include a second hormone or factor in grandicollis group species that functions
      either alone or with JH III; in both cases acting after HMG-R has been
      transcribed.

PMID- 15724967
TI  - Introgressing pheromone QTL between species: towards an evolutionary
      understanding of differentiation in sexual communication.
AB  - As a first step toward understanding how noctuid moths evolve species-specific
      pheromone communication systems, we hybridized and back-crossed two closely
      related moth species, Heliothis virescens (Hv) and H. subflexa (Hs), which differ
      qualitatively and quantitatively in their multicomponent sex pheromone blends. We
      used amplified fragment length polymorphism (AFLP) marker-based mapping of
      backcross families to determine which of the 30 autosomes in these moths
      contained quantitative trait loci (QTL) controlling the percentages of specific
      chemical components in the pheromone blends. In two previous backcrosses to Hs,
      we found a strong depressive effect of Hv-chromosome 22 on the percentage of
      three acetate components in the pheromone gland. These acetates are present in Hs
      and absent in Hv. Here, we describe how we introgressed Hv-chromosome 22 into the
      genomic background of Hs. Selection for Hv-chromosome 22 started from backcross 3
      (BC3) females. All females that had Hv-chromosome 22 and a low percentage of
      acetates (<3% of the total amount of pheromone components present) were
      backcrossed to Hs males. In BC5 to BC8, we determined whether Hv-chromosome 22
      was present by a) running only the primer pairs that would yield the markers for
      that chromosome, and/or b) determining the relative percentages of acetates in
      the pheromone glands. Either or both genotype and phenotype were used as a
      criterion to continue to backcross these females to Hs males. In BC9, we
      confirmed the isolation of Hv-chromosome 22 in the Hs genomic background, and
      backcrossed the males to Hs females to eliminate the Hv-sex chromosome as well as
      mitochondrial DNA. The pheromone composition was determined in BC3, BC5, and BC11
      females with and without Hv-chromosome 22. All backcross females with Hv
      chromosome 22 contained significantly less acetates than females without this
      chromosome. In addition, BC3 females with Hv-chromosome 22 contained
      significantly more Z11-16:OH than BC3 females without Hv-chromosome 22. However,
      in BC5 and BC11 females, the correlation between Z11-16:OH and Hv-chromosome 22
      was lost, suggesting that there are separate QTL for the acetates and for Z11
      16:OH, and that the relative amount of the alcohol component is only affected in
      epistasis with other (minor) QTL. Now that we have succeeded in isolating the
      chromosome that has a major effect on acetate production, we can test in
      behavioral experiments whether the presence of acetates may have been a driving
      force for a shift in pheromone composition. Such tests are necessary to move
      towards an evolutionary understanding of the differentiation in sexual
      communication in Heliothis spp. moths.

PMID- 15724968
TI  - Effect of host defense chemicals on clonal distribution and performance of
      different genotypes of the cereal aphid Sitobion avenae.
AB  - Five microsatellite loci were used to study the genetic variability and
      population structure of Sitobion avenae (Hemiptera: Aphididae) on some of its
      host plants. Individuals were collected in Chile from different cultivated and
      wild Poaceae. Forty-four multilocus genotypes were found among the 1052 aphids
      analyzed, of which four represented nearly 90% of the sample. No specialist
      genotypes were found, although some preferred hosts endowed with chemical
      defenses, i.e., hydroxamic acids (Hx), while others preferred comparatively
      undefended hosts. Performances of some predominant and some rare genotypes were
      evaluated on plants differing in their Hx levels. Significant differences in
      performance were found among clones, the two most common genotypes showing no
      differences in performance among all hosts tested, and the rare genotypes showing
      enhanced performance on the host with highest Hx level. A hypothesis is proposed
      whereby the appearance of rarer genotypes is in part related to the presence of
      Hx.

PMID- 15724969
TI  - Acquired and R-gene-mediated resistance against the potato aphid in tomato.
AB  - We examined the effects of three forms of host plant resistance in tomato,
      Lycopersicon esculentum, on the potato aphid, Macrosiphum euphorbiae. Mi-1.2, a
      resistance gene (R-gene) in tomato that deters aphid feeding, reduced the
      population growth of both potato aphid isolates tested, although it appeared to
      have a greater impact on isolate WU11 than on isolate WU12. The results suggest
      that there may be quantitative differences in virulence between these two aphid
      isolates. We also examined two distinct forms of acquired resistance in tomato,
      jasmonic acid (JA)-dependent and salicylic acid (SA)-dependent induced defenses.
      Exogenous foliar application of JA triggered expression of a JA-inducible
      proteinase inhibitor in tomato cultivars with and without Mi-1.2, although the
      effects of treatment on aphid performance differed between these cultivars. JA
      treatment reduced aphid population growth on a susceptible tomato cultivar that
      lacks Mi-1.2, but did not significantly enhance or inhibit aphid control on a
      near-isogenic resistant tomato cultivar that carries this gene. Foliar
      application of an SA analog, benzothiadiazole (BTH), was used to induce SA
      dependent defenses. BTH treatment reduced the population growth of both aphid
      isolates on a susceptible tomato cultivar, and also enhanced aphid control on a
      resistant cultivar. The results indicate that both SA- and JA-dependent acquired
      resistance in tomato have a direct negative effect on a phloem-feeding insect.
      Furthermore, this study demonstrates that acquired resistance and R-gene-mediated
      resistance can interact for enhanced suppression of insect herbivores.

PMID- 15724970
TI  - Maize genes induced by herbivory and volicitin.
AB  - In crop plants, both mechanical damage and insect attack trigger rapid changes in
      gene transcription. We investigated whether insect herbivory differs from a
      general wound response, and if so, is the induction specific to the pest/host
      plant interaction? Herbivory by beet armyworm (BAW; Spodoptera exigua)
      caterpillars on maize results in a unique pattern of volatile compounds not
      triggered by wounding alone that attracts the generalist parasitoid Cotesia
      marginiventris. Caterpillar-induced volatile emission can be mimicked when a
      component of the BAW oral secretions (N-(17-hydroxylinolenoyl)-L-glutamine)
      termed volicitin, is applied to wounded leaves. We identified genes that are
      affected by BAW feeding by comparing volicitin treatment with wounding alone. We
      compared cDNAs from these two populations by isolating genes from a subtractive
      library and using reverse northerns. Virtual northern blots confirmed these
      results and further showed that BAW infestation affected the expression of these
      genes. In some cases, BAW feeding inhibited the expression of volicitin-induced
      genes, suggesting the role of additional bioactive components in caterpillar
      regurgitate. Transcripts involved in volatile production are increased by
      volicitin and BAW infestation treatments, and are also detectable at low levels
      in mechanically wounded leaves. Finally, we identified three new sesquiterpene
      cyclase genes that are induced by volicitin.

PMID- 15724971
TI  - Diet-mediated inter-colonial aggression in the formosan subterranean termite
      Coptotermes formosanus.
AB  - In most social insects, intercolonial and interspecific aggression are
      expressions of territoriality. In termites, cuticular hydrocarbons (CHCs) have
      been extensively studied for their role in nestmate recognition and aggressive
      discrimination of nonnest-mates. More recently, molecular genetic techniques have
      made it possible to determine relatedness between colonies and to investigate the
      influence of genetics on aggression. In the Formosan subterranean termite,
      Coptotermes formosanus, however, the role of CHCs and genetic relatedness in
      inter-colony aggression has been ambiguous, suggesting the involvement of
      additional factors in nest-mate recognition. In this study we assess the range of
      aggression in this termite species and characterize the influence of genetic
      relatedness, CHC profiles and diet on aggression levels. We collected four
      colonies of C. formosanus, feeding either on bald cypress or birch, from three
      locations in Louisiana. Inter-colony aggression ranged from low to high.
      Differences in CHC profiles, as well as genetic distances between colonies
      determined by using microsatellite DNA markers, showed no significant correlation
      with aggression. However, termite diet (host tree) played a significant role in
      determining the level of aggression. Thus, two distantly related colonies, each
      feeding on different diets, showed high aggression that significantly diminished
      if they were fed on the same wood in the laboratory (spruce). Using headspace
      solid phase microextraction, we found three compounds from workers fed on birch
      that were absent in workers fed on spruce. Such diet-derived chemicals may be
      involved in the complex determination of nest-mate recognition in C. formosanus.

PMID- 15724972
TI  - Sonochemical preparation of hollow nanospheres and hollow nanocrystals.
AB  - Ceramic hollow spheres of MoS2 and MoO3 were obtained by sonochemical synthesis
      of MoS2 and MoO3 templated on silica nanoparticles (diameters 50-500 nm) followed
      by acid etching to remove the silica core. The resulting hollow materials have
      been characterized by elemental analysis, XPS, SEM, TEM, optical absorption, and
      hydrodesulfurization (HDS) studies. The TEM studies on the hollow ceramic
      materials indicate the formation of dispersed free spheres with a hollow core.
      The hollow materials obtained from thermally treated MoS2/SiO2 (450-700 degrees
      C) show the formation of layered MoS2 (lattice fringes approximately 6.2 A) with
      a wall thickness of 6-8 layers. The MoS2 hollow spheres are extremely active
      catalysts for the HDS of thiophene. Hollow spheres of MoO3 are prepared in a
      similar fashion. Surprisingly, upon heating, hollow crystals of MoO3 with sharp
      edged truncated cubes containing inner voids are formed from the initial spheres.

PMID- 15724973
TI  - (67)Zn NMR chemical shifts and electric field gradients in zinc complexes: a
      quantum chemical investigation.
AB  - We have used quantum chemical methods to predict 67Zn NMR chemical shifts as well
      as quadrupole coupling constants (CQ) in a series of biomimetic and inorganic
      zinc complexes. The 67Zn chemical shifts are predicted with an R2 = 0.975,
      corresponding to a 24.3 ppm or 6.7% error over the entire 365 ppm 67Zn chemical
      shift range. The 67Zn CQ values are predicted with an R2 = 0.991, corresponding
      to a 1.17 MHz or 3.0% error over the entire 38.75 MHz range. The 67Zn NMR shifts
      in a series of complexes containing N,O ligands are, in general, highly
      correlated with the number of oxygen ligands. The ability to compute 67Zn NMR
      shifts as well as CQ values opens up the possibility of using both of these
      properties in structure determination or refinement in proteins.

PMID- 15724974
TI  - Searching for DDAH inhibitors: S-nitroso-L-homocysteine is a chemical lead.
AB  - The cysteine-hydrolase dimethylargininase-1 (DDAH-1) is an important regulator of
      NO production in mammalian tissue for which the availability of an inhibitor for
      clinics and research would be most appreciated. While studying the effect of the
      endogenously occurring S-nitroso-l-homocysteine on DDAH-1, an unusual N
      thiosulfoximide modification was identified in the active site of the enzyme.
      Thus, S-nitroso-l-homocysteine in combination with the mechanism proposed herein
      offers a basis for the rational design of DDAH inhibitors.

PMID- 15724975
TI  - Microhydration of Guanine base pairs.
AB  - We report spectroscopy of clusters of guanine base pairs with one and two water
      molecules. We recorded the vibronic spectra of the mass-selected GG(H2O) and
      GG(H2O)2 clusters using resonant two photon ionization (R2PI) and we used IR-UV
      double resonance spectroscopy to obtain ground state IR spectra of these
      clusters. We found that a single water molecule stabilizes one of two structures
      we had previously found for guanine dimers. Addition of a second water molecule
      causes no further structural change.

PMID- 15724977
TI  - A general low-temperature route for large-scale fabrication of highly oriented
      ZnO nanorod/nanotube arrays.
AB  - Large-scale arrays of highly oriented hexagonal ZnO nanorods and nanotubes were
      fabricated on arbitrary ZnO-film-coated substrates using a low-temperature
      chemical-liquid-phase deposition method. The obtained nanoproducts were
      characterized, and the growth mechanism is proposed.

PMID- 15724976
TI  - Selective small molecules blocking HIV-1 Tat and coactivator PCAF association.
AB  - Development of drug resistance from mutations in the targeted viral proteins
      leads to continuation of viral production by chronically infected cells,
      contributing to HIV-mediated immune dysfunction. Targeting a host cell protein
      essential for viral reproduction, rather than a viral protein, may minimize the
      viral drug resistance problem as observed with HIV protease inhibitors. We report
      here the development of a novel class of N1-aryl-propane-1,3-diamine compounds
      using a structure-based approach that selectively inhibit the activity of the
      bromodomain of the human transcriptional co-activator PCAF, of which association
      with the HIV trans-activator Tat is essential for transcription and replication
      of the integrated HIV provirus.

PMID- 15724978
TI  - Unusually high performance photovoltaic cell based on a [60]fullerene metal
      cluster-porphyrin dyad SAM on an ITO electrode.
AB  - A self-assembled monolayer (SAM) of a C60-triosmium cluster complex
      Os3(CO)7(CNR)(CNR')(mu3-eta2:eta2:eta2-C60) (ZnP-C60; R = (CH2)3Si(OEt)3, R' =
      ZnP) on an ITO surface exhibits ideal electrochemical responses as well as
      remarkable enhancement of the photocurrent generation. The diazabicyclooctane
      (DABCO) binding (ZnP)-C60/ITO/AsA/Pt cell shows the highest photocurrent
      generation quantum yield (19.5%) ever reported for the molecular photovoltaic
      cells based on the covalently linked donor-acceptor dyad structures. The high
      efficiency in photocurrent generation is ascribed to an efficient electron
      transfer from photoexcited porphyrin to fullerene, revealed by fluorescence
      lifetime measurements and transient absorption decay profiles. These results
      provide valuable information on the new strategy for the construction of
      molecular photonic devices and artificial photosynthetic systems on ITO
      electrodes.

PMID- 15724979
TI  - Mixed valence isomers.
AB  - The infrared spectroscopic observation of mixed valence isomers, the two
      alternate charge distributions of a mixed valence complex, is reported. Asymmetry
      induced by the 2-methylpyrazine bridging ligand was used to energetically
      differentiate the two states, and isotopic labeling of CO was used to
      spectroscopically observe the two states. Infrared line shape analysis was used
      to determine rate constants for electron transfer of 6.5 x 1011 s-1 and
      equilibrium constants of 2.2 for the mixed valence isomers.

PMID- 15724980
TI  - Can block copolymers be synthesized by a single-step chemoenzymatic route in
      supercritical carbon dioxide?
AB  - We demonstrate the single-step one-pot synthesis of block copolymers by
      simultaneous enzymatic ring-opening polymerization and chemically catalyzed atom
      transfer radical polymerization in supercritical carbon dioxide. Both catalyst
      systems function simultaneously under these conditions, providing a simple route
      to the formation of block copolymers of dissimilar monomers.

PMID- 15724981
TI  - Large gate modulation in the current of a room temperature single molecule
      transistor.
AB  - We have demonstrated a single molecule field effect transistor (FET) which
      consists of a redox molecule (perylene tetracarboxylic diimide) covalently bonded
      to a source and drain electrode and an electrochemical gate. By adjusting the
      gate voltage, the energy levels of empty molecular states are shifted to the
      Fermi level of the source and drain electrodes. This results in a nearly 3 orders
      of magnitude increase in the source-drain current, in the fashion of an n-type
      FET. The large current increase is attributed to an electron transport mediated
      by the lowest empty molecular energy level when it lines up with the Fermi level.

PMID- 15724982
TI  - Synthesis of planar chiral phosphapalladacycles by highly enantioselective
      transcyclopalladation.
AB  - The first highly enantioselective synthesis of planar chiral ferrocene
      phosphapalladacycles was performed by high-yielding asymmetric
      transcyclopalladation with cobalt oxazoline palladacycles (COP). Use of di-mu
      acetatobis[(eta5-(S)-(pR)-2-(2'-(4'-isopropyl)oxazolinyl)cyclopentadienyl
      C1,N3')(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium(II), followed by
      acetate/chloride ligand exchange, gave (pS)-di-mu-chloro[2-(2
      dicyclohexylphosphino)phenylferroene-C1,P)dipalladium(II) (95% ee). Similarly,
      diastereomeric di-mu-acetatobis[(eta5-(S)-(pS)-2-(2'-(4'-tert
      butyl)oxazolinyl)cyclopentadienyl-C1,N3')(eta4
      tetraphenylcyclobutadiene)cobalt]dipalladium(II) led to the enantiomeric (pR)
      phosphapalladacycle (95% ee), revealing the control of these reactions by the
      element of planar chirality in COP. The reactions were extended to the synthesis
      of (pS)- and (pR)-di-mu-chloro[2-(2-diphenylphosphino)phenylferroene
      C1,P)dipalladium(II) (78 and 92% ee, respectively). In all cases, the palladium
      free precursors to COP were recovered for recycling.

PMID- 15724983
TI  - Enantioselective radical addition/trapping reactions with alpha,beta
      disubstituted unsaturated imides. Synthesis of anti-propionate aldols.
AB  - This manuscript describes a highly diastereo- and enantioselective intermolecular
      radical addition/hydrogen atom transfer to alpha,beta-disubstituted enoates.
      Additionally, we show that anti-propionate aldol-like products can be easily
      prepared from alpha-methyl-beta-acyloxyenoates in good yields and high diastereo-
      and enantioselectivities.

PMID- 15724984
TI  - 55Mn pulse ENDOR at 34 GHz of the S0 and S2 states of the oxygen-evolving complex
      in photosystem II.
AB  - 55Mn pulse ENDOR experiments at 34 GHz (Q-band) are reported for the S0 and S2
      states of the oxygen-evolving complex of photosystem II. Their numerical analysis
      (i) shows that in both states all four Mn ions are magnetically coupled, (ii)
      allows a refinement of the hyperfine interaction (HFI) parameters obtained
      earlier for the S2 state at X-band (Peloquin, J. M.; Campbell, K. A.; Randall, D.
      W.; Evanchik, M. A.; Pecoraro, V. L.; Armstrong, W. H.; Britt, R. D. J. Am. Chem.
      Soc. 2000, 122, 10926-10942), (iii) provides the first reliable 55Mn HFI tensors
      for the S0 state, and (iv) leads to the suggestion that the Mn oxidation states
      in S0 and S2 are Mn4(III, III, III, IV) and Mn4(III, IV, IV, IV), respectively.
      In addition, a Q-band EPR spectrum is reported for the S0 state, and inversion
      recovery experiments at 4.5 K directly show that the electron spin-lattice
      relaxation for the S0 state is about 2 orders of magnitude faster than that for
      the S2 state.

PMID- 15724985
TI  - Terminal phosphate-labeled nucleotides with improved substrate properties for
      homogeneous nucleic acid assays.
AB  - Nucleotides with a dye attached to the terminal phosphate with four or more
      phosphates (tetra- or pentaphosphates) are superior substrates than the
      corresponding triphosphates for DNA and RNA polymerases. When fluorogenic dyes
      are directly attached to the terminal phosphate, they can be released by the
      action of polymerase and alkaline phosphatase. The released dye changes color and
      fluorescence properties. The fluorescent signal can also be amplified by using
      multiple labeled nucleotides to detect small amounts of template. We have
      explored the utility of these nucleotides in a variety of applications including
      homogeneous SNP detection methods, DNA sequencing, and quantitation of PCR and
      RCA.

PMID- 15724987
TI  - Room temperature ionic liquids from 20 natural amino acids.
AB  - We first succeeded in synthesizing ionic liquids from 20 natural amino acids.
      Amino acid ionic liquids dissolved native amino acids, despite water-free
      conditions. Furthermore, these ionic liquids are soluble in various organic
      solvents, such as chloroform. Effects of acidity, hydrogen bonding ability, and
      steric factors on the properties of these ionic liquids were analyzed as the
      function of side groups.

PMID- 15724986
TI  - Peptide-cleaving catalyst selective for peptide deformylase.
AB  - A peptide-cleaving catalyst selective for peptide deformylase (PDF) was obtained
      from a library containing about 15 000 catalyst candidates. The catalyst cleaved
      the polypeptide backbone of PDF at Gln(152)-Arg(153). Docking simulations
      suggested multiple modes of interactions in the complex formed between the
      catalyst and PDF.

PMID- 15724988
TI  - Folding directed N-oxidation of oligopyridine-dicarboxamide strands and
      hybridization of oxidized oligomers.
AB  - Folding of oligopyridine-dicarboxamides into helices inhibits the N-oxidation of
      pyridine rings central in the sequence and also much enhances the N-oxidation of
      pyridine rings peripheral in the sequence. Oligomers N-oxidized at their terminal
      position show an increased ability to hybridize into double helices.

PMID- 15724989
TI  - Photoinduced deformation of amphiphilic azo polymer colloidal spheres.
AB  - Photoinduced shape deformation of colloidal spheres made of an amphiphilic azo
      polymer has been demonstrated in this work. The polymer contains the donor-and
      acceptor-type azobenzene chromophores and can form uniform colloidal spheres by
      dropwise adding water into its THF solution. When the colloidal spheres obtained
      were exposed to the interfering p-polarized Ar+ laser beams (150 mW/cm2), the
      colloidal spheres changed to prolates (i.e., "rugby-balls"), "spindles", and
      finally "rods", depending on the irradiation times. The elongated direction of
      the spheres was observed to be the same as the polarization direction of the
      laser beam. The average major-to-minor ratio of the ellipsoids could be easily
      adjusted by controlling the irradiation time. The deformation effect observed in
      this work can offer a new way to prepare nonspherical colloids from colloidal
      spheres and will shed new light on the correlation between the photodriven shape
      deformation and photoinduced surface relief gratings for the same type of
      polymers.

PMID- 15724990
TI  - New aspects of diphenylbutadiene photochemistry. Regiospecific hula-twist
      photoisomerization.
AB  - In EPA glass at liquid nitrogen temperature, the E,E isomer of diphenylbutadiene
      (DPB) was photostable, while both the Z,E and Z,Z isomers underwent selective HT
      isomerization at center 1 giving the stable conformer of the double-bond
      isomerized trans product. That HT-1 was involved rather than the OBF process was
      shown by results of o,o'-dimethyl-DPB. Formation of unstable trans product
      corresponded to simultaneous configurational and conformational isomerization.
      The regioselectivity was found not sensitive to a substituent effect, as shown by
      the similar reactivity in p,p'- or o,o'-bistrifluoromethyl-DPB.

PMID- 15724991
TI  - High-performance, stable organic thin-film field-effect transistors based on bis
      5'-alkylthiophen-2'-yl-2,6-anthracene semiconductors.
AB  - The development of new organic semiconductors with improved electrical
      performance and enhanced environmental stability is the focus of considerable
      research activity. This communication presents the design, synthesis, and device
      stability data for novel bis-5'-alkylthiophen-2'yl-2,6-anthracene organic
      semiconductors. When incorporated into thin-film field-effect transistors,
      mobilities as high as 0.5 cm2/Vs and on/off current ratios greater than 107 are
      observed. We have investigated device stability in terms of both shelf life and
      operating lifetime. Devices incorporating the reported semiconductors display an
      average field-effect mobility of 0.4 cm2/Vs for DHTAnt and an on/off current
      ratio of 106 even after 15 months of storage. Furthermore, there is no decrease
      in performance during continuous operation of the devices over several thousand
      cycles.

PMID- 15724992
TI  - Unprecedented chemistry of an aryloxychlorodiazirine: generation of a
      dihalodiazirine and diazirinone.
AB  - The reaction of p-nitrophenoxychlorodiazirine with tetrabutylammonium fluoride
      follows three channels: (1) approximately 17% of p-nitrophenoxide/fluoride
      exchange to chlorofluorodiazirine and p-nitrophenol, (2) approximately 28% of
      Cl/F exchange to p-nitrophenoxyfluorodiazirine, and (3) approximately 55% of ipso
      fluoride attack, affording p-nitrofluorobenzene and the previously unknown
      diazirinone (diazacyclopropenone).

PMID- 15724993
TI  - A lipophilic hexaporphyrin assembly supported on a stannoxane core.
AB  - Lipophilic hexaporphyrin free-base and copper-metalated assemblies supported on a
      Sn6O6 core have been synthesized and characterized. The nuclease activity of the
      copper derivative has been studied.

PMID- 15724994
TI  - The synthesis of (-)-isodomoic acid C.
AB  - The neuroactive algal metabolite (-)-isodomoic acid C, a kainoid amino acid, has
      been synthesized for the first time. Asymmetric dearomatizing cyclization of an
      aromatic amide using a chiral lithium amide base generates a bicyclic enone
      containing a pyrrolidinone ring with the relative and absolute stereochemistry of
      the target. A further 15 synthetic steps, including conjugate cuprate addition to
      the enone of a side chain precursor, a Ru-promoted oxidation of the phenyl ring
      to the C2-carboxylic acid substituent, a regioselective Baeyer-Villiger reaction,
      and an E-selective Horner-Wadsworth-Emmons reaction, elaborate the cyclization
      product into the target molecule.

PMID- 15724995
TI  - Structure-dependent modulation of a pathogen response in plants by synthetic O
      antigen polysaccharides.
AB  - Many phytopathogenic bacteria display lipopolysaccharides (LPS) with the O-chain
      repeating unit [alpha-l-Rha-(1-->3)-alpha-l-Rha-(1-->3)-alpha-l-Rha-(1-
      >2)](n)(). This trisaccharide unit was synthesized and oligomerized to obtain
      hexa- and nonasaccharides. The deprotected rhamnans were effective in suppressing
      the hypersensitive response (HR) and in inducing PR-1 gene expression in
      Arabidopsis thaliana. Conformational analysis of the oligorhamnans by NMR
      spectroscopy and molecular dynamics calculations revealed that a coiled structure
      develops with increasing chain length of the oligosaccharide. This is associated
      with increasing efficacy in HR suppression and PR-1 gene expression. We therefore
      infer that the coiled structure of phytopathogenic bacteria is a plant
      recognizable pathogen-associated molecular pattern (PAMP).

PMID- 15724996
TI  - Simultaneous binding of meso-tetrakis(N-methylpyridinium-4-yl)porphyrin and 4',6
      diamidino-2-phenylindole at the minor grooves of poly(dA).poly(dT) and poly[d(A
      T)(2)]: fluorescence resonance energy transfer between DNA bound drugs.
AB  - The spectral properties of meso-tetrakis(N-methylpyridinium-4-yl)porphyrin
      (TMPyP) bound to poly(dA).poly(dT) and poly[d(A-T)(2)] in the presence and in the
      absence of 4',6-diamidino-2-phenylindole (DAPI) have been studied. DAPI fits
      deeply into the minor groove of both poly(dA).poly(dT) and poly[d(A-T)(2)], and
      TMPyP is also situated at the minor groove. The nature of the absorption,
      circular dichroism (CD), and flow linear dichroism (LD) spectra of the TMPyP
      poly(dA).poly(dT) and -poly[d(A-T)(2)] complexes in the Soret band is essentially
      unaffected whether the minor groove is blocked by DAPI or not, although small
      variations been noticed in the presence of DAPI. Furthermore, a close analysis of
      the reduced LD spectrum in the Soret band results in angles of approximately 80
      degrees and 55 degrees between transition moments of the TMPyP and DNA helix axes
      in the absence of DAPI. All these observations indicate that the side of TMPyP
      whose structure resembles that of classical minor groove binding drugs does not
      fit deeply into the minor groove. This suggests that TMPyP binds across the minor
      groove: two positively charged pyridiniumyl rings interact electrostatically with
      negatively charged phosphate groups of DNA. When DAPI and TMPyP are
      simultaneously bound to poly(dA).poly(dT) or poly[d(A-T)(2)], the fluorescence
      intensity of DAPI decreases as TMPyP concentration increases, indicating that the
      excited energy of DAPI is transferred to TMPyP.

PMID- 15724997
TI  - Investigation of a putative mobius aromatic hydrocarbon. The effect of
      benzannelation on mobius [4n]annulene aromaticity.
AB  - The first experimental example of a [4n]annulene derivative with one Mobius
      twist, 1, was synthesized recently [Ajami, D.; Oeckler, O.; Simon, A.; Herges, R.
      Nature 2003, 426, 819] and was purported to possess aromatic character. However,
      critical analysis of the published crystallographic data indicates that the
      Mobius [16]annulene core of 1 shows large bond alternation (Deltar up to 0.157
      A). Delocalization in this core is inhibited by large dihedral angles, which
      hinders effective pi overlap. This conclusion is supported by computational
      results (B3LYP/6-311+G) on 1 and several less benzannelated derivatives, based on
      geometric (Deltar, Deltar(m), Julg A, HOMA) and magnetic (NICS, magnetic
      susceptibility exaltation) criteria of aromaticity. That benzannelation results
      in bond localization in the [16]annulene core is shown by additional computations
      on benzannelated derivatives of other Mobius aromatic species. Additionally, the
      aromatic stabilization energy (ASE) of 1 has been reinvestigated using two
      different procedures. Evaluation of uncorrected ISE(II) values of just the
      polyene bridge portion of 1 and its Huckel counterpart suggests that
      stabilization of 1 relative to its Huckel isomer is confined to the polyene
      bridge and is not due to a delocalized pi circuit. Furthermore, application of s
      cis/s-trans corrections lowers the ISE(II) value of 1 from 4.0 kcal/mol to 0.6
      kcal/mol, suggesting that 1 is nonaromatic.

PMID- 15724998
TI  - Photoisomerization mechanism of 11-cis-locked artificial retinal chromophores:
      acceleration and primary photoproduct assignment.
AB  - CASPT2//CASSCF/6-31G photochemical reaction path computations for two 4-cis-nona
      2,4,6,8-tetraeniminium cation derivatives, with the 4-cis double bond embedded in
      a seven- and eight-member ring, are carried out to model the reactivity of the
      corresponding ring-locked retinal chromophores. The comparison of the excited
      state branches of the two reaction paths with that of the native chromophore, is
      used to unveil the factors responsible for the remarkably short (60 fs) excited
      state (S(1)) lifetime observed when an artificial rhodopsin containing an eight
      member ring-locked retinal is photoexcited. Indeed, it is shown that the strain
      imposed by the eight-member ring on the chromophore backbone leads to a dramatic
      change in the shape of the S(1) energy surface. Our models are also used to
      investigate the nature of the primary photoproducts observed in different
      artificial rhodopsins. It is seen that only the eight member ring-locked retinal
      model can access a shallow energy minimum on the ground state. This result
      implies that the primary, photorhodopsin-like, transient observed in artificial
      rhodopsins could correspond to a shallow excited state minimum. Similarly, the
      second, bathorhodopsin-like, transient species could be assigned to a ground
      state structure displaying a nearly all-trans conformation.

PMID- 15724999
TI  - Base-catalyzed hydrogenation: rationalizing the effects of catalyst and substrate
      structures and solvation.
AB  - Ab initio molecular orbital calculations have been used to study the base
      catalyzed hydrogenation of carbonyl compounds. It is found that these
      hydrogenation reactions share many common features with S(N)2 reactions. Both
      types of reactions are described by double-well energy profiles, with deep wells
      and a low or negative overall energy barrier in the gas phase, while the solution
      phase profiles show very shallow wells and much higher barriers. For the
      hydrogenation reactions, the assembly of the highly ordered transition structure
      is found to be a major limiting factor to the rate of reaction. In the gas phase,
      the overall barriers for reactions catalyzed by Group I methoxides increase
      steadily down the group, due to the decreasing charge density on the metal. On
      the other hand, for Group II and Group III metals, the overall barriers decrease
      down the group, which is attributed to the increasing ionic character of the
      metal-oxygen bond. The reaction with B(OCH(3))(3) has an exceptionally high
      barrier, which is attributed to pi-electron donation from the oxygen lone pairs
      of the methoxy groups to the formally vacant p orbital on B, as well as to the
      high covalent character of the B-O bonds. In solution, these reactivity trends
      are generally the opposite of the corresponding gas-phase trends. While similar
      barriers are obtained for reactions catalyzed by methoxides and by tert
      butoxides, reactions with benzyloxides have somewhat higher barriers. Aromatic
      ketones are found to be more reactive than purely aliphatic ketones. Moreover,
      comparison between catalytic hydrogenation of 2,2,5,5-tetramethylcyclopentanone
      and pivalophenone shows that factors such as steric effects may also be important
      in differentiating their reactivity. Solvation studies with a wide range of
      solvents indicate a steady decrease in barrier with decreasing solvent dielectric
      constant, with nonpolar solvents generally leading to considerably lower barriers
      than polar solvents. In practice, a good balance between polarity and catalyst
      solubility is required in selecting the most suitable solvent for the base
      catalyzed hydrogenation reaction.

PMID- 15725000
TI  - Optical activity induced by helical arrangements of tryptamine and 4
      chlorobenzoic acid in their cocrystal.
AB  - Optical rotatory powers of chiral cocrystals formed from the achiral molecules
      tryptamine and 4-chlorobenzoic acid were determined by the HAUP (high accuracy
      universal polarimeter) method. These cocrystals belonged to space group
      P2(1)2(1)2(1), and their absolute configuration was confirmed by the Flack
      parameter. In the M-crystal, 2-fold helical arrangements are formed in a
      counterclockwise direction between the two components through the quaternary
      ammonium salt bridge, hydrogen bond, and the aromatic pi-piinteraction along the
      c axis, while clockwise helices alone exist in the P-crystal. Large rotatory
      powers rho(3)(M) = -355 and rho(3)(P) = +352 deg mm(-)(1) were obtained along the
      c axis in the M- and P-crystal, respectively, at 632.8 nm and 303 K. The
      magnitude was 10 to 100 times larger than those for ordinary organic crystals.
      Further, it was confirmed that the negative sign was induced by the
      counterclockwise helical structures and the positive sign by the clockwise
      helices. In contrast, the rotations along the a and b axis which are in
      perpendicular directions to the screw axis were rho(1)(M) = +138, rho(1)(P) = 
      140 deg mm(-)(1), and rho(2)(M) = -56, rho(2)(P) = +58 deg mm(-)(1), much smaller
      than rho(3)(M) and rho(3)(P) . The results revealed that the helically arranged
      aromatic pi electrons as well as the helical ionic and hydrogen bond networks in
      the crystal contributed to the enhancement of the magnitude of these rotations.

PMID- 15725001
TI  - Structure-property relationships of donor/acceptor-functionalized
      tetrakis(phenylethynyl)benzenes and bis(dehydrobenzoannuleno)benzenes.
AB  - A series of tetrakis(phenylethynyl)benzenes and bis(dehydrobenzoannuleno)benzenes
      have been synthesized containing tetra-substitutions of neutral, donor, and mixed
      donor/acceptor groups. To ascertain the importance of substitutional and
      structural differences of the phenylacetylenes, the optical absorption and
      emission properties of each series were examined. Conjugation effectiveness,
      electron density, planarity, and geometry of charge-transfer pathways were found
      to have a pronounced effect on the overall optical and material properties.
      Considerable self-association behavior due to face-to-face stacking in solution
      was observed for donor/acceptor-functionalized macrocycles and was quantified by
      concentration-dependent (1)H NMR measurements. A solvent-dependent polymerization
      of one macrocycle regioisomer was observed and characterized. To provide further
      insight into the energy levels and electronic transitions present, computational
      studies of each system were performed.

PMID- 15725003
TI  - Steric and electronic properties of N-heterocyclic carbenes (NHC): a detailed
      study on their interaction with Ni(CO)4.
AB  - N-heterocyclic carbene ligands IMes (1), SIMes (2), IPr (3), SIPr (4), and ICy
      (5) react with Ni(CO)(4) to give the saturated tricarbonyl complexes
      Ni(CO)(3)(IMes) (8), Ni(CO)(3)(SIMes) (9), Ni(CO)(3)(IPr) (10), Ni(CO)(3)(SIPr)
      (11), and Ni(CO)(3)(ICy) (12), respectively. The electronic properties of these
      complexes have been compared to their phosphine analogues of general formula
      Ni(CO)(3)(PR(3)) by recording their nu(CO) stretching frequencies. While all of
      these NHCs are better donors than tertiary phosphines, the differences in donor
      properties between ligands 1-5 are surprisingly small. Novel, unsaturated
      Ni(CO)(2)(IAd) (13) and Ni(CO)(2)(I(t)()Bu) (14) compounds are obtained from the
      reaction of Ni(CO)(4) with IAd (6) and I(t)()Bu (7). Complexes 13 and 14 are
      highly active toward substitution of the NHC as well as the carbonyl ligands.
      This has allowed the determination of Ni-C(NHC) bond dissociation energies and
      the synthesis of various unsaturated Ni(0) and Ni(II) complexes. Computational
      studies on compounds 8-14 are in line with the experimental findings and show
      that IAd (6) and I(t)()Bu (7) are more bulky than IMes (1), SIMes (2), IPr (3),
      SIPr (4), and ICy (5). Furthermore, a method based on %V(bur) values has been
      developed for the direct comparison of steric requirements of NHCs and tertiary
      phosphines. Complexes 8-14, as well as NiCl(C(3)H(5))(I(t)()Bu) (16) and
      NiBr(C(3)H(5))(I(t)()Bu) (17), have been characterized by X-ray crystallography.

PMID- 15725002
TI  - Fluorescent cocaine probes: a tool for the selection and engineering of
      therapeutic antibodies.
AB  - Cocaine is a highly addictive drug, and despite intensive efforts, effective
      therapies for cocaine craving and addiction remain elusive. In recent years, we
      and others have reported advances in anti-cocaine immunopharmacotherapy based on
      specific antibodies capable of sequestering the drug before it reaches the brain.
      In an effort to obtain high affinity therapeutic anti-cocaine antibodies, either
      whole IgGs or other antibody constructs, fluorescence spectroscopic techniques
      could provide a means of assisting selection and engineering strategies. We
      report the synthesis of a series of cocaine-fluorophore conjugates (GNC-F1, GNC
      F2, GNC-I) and the functional evaluation of these compounds against single-chain
      Fv antibodies obtained via crystallographic analysis/engineering and against
      commercially available anti-cocaine monoclonal antibodies with a wide range of
      cocaine-binding affinities. From these studies, we determined that the GNC-F2
      fluorophore reproduced affinity constants obtained using [(3)H]-labeled cocaine.
      We anticipate that the readily synthesized and nonradioactive GNC-F2 will find
      use both as a tool for bioimaging and in the high-throughput selection and
      engineering of potential therapeutic antibodies against cocaine.

PMID- 15725004
TI  - Size-dependent dissociation pH of thiolate ligands from cadmium chalcogenide
      nanocrystals.
AB  - A method, pseudo steady-state titration, is introduced for determining the
      precipitation pH of nanocrystals coated by electron-donating ligands. CdSe
      nanocrystals coated with hydrophilic deprotonated thiol (thiolate) ligands were
      studied systematically. For comparison, CdTe and CdS nanocrystals coated with the
      same types of ligands were also examined. The results show that the precipitation
      of the nanocrystals is caused by the dissociation of the nanocrystal-ligand
      coordinating bonds from the nanocrystal surface. The ligands are removed from the
      surface due to protonation in a relatively low pH range, between 2 and 7
      depending on the size, approximately within the quantum confinement size regime,
      and chemical composition (band gap) of the nanocrystals. In contrast, the
      redispersion of the nanocrystals was found to be solely determined by the
      deprotonation of the ligands. The size-dependent dissociation pH of the ligands
      was tentatively used as a means for determining the size-dependent free energy
      associated with the formation of a nanocrystal-ligand coordinating bond.

PMID- 15725005
TI  - Catalytically active mu-Oxodiiron(IV) oxidants from Iron(III) and dioxygen.
AB  - The reaction between an Fe(III) complex and O(2) to afford a stable catalytically
      active diiron(IV)-mu-oxo compound is described. Phosphonium salts of orange five
      coordinated Fe(III)-TAML complexes with an axial aqua ligand ([PPh(4)]1-H(2)O,
      tetraamidato macrocyclic Fe(III) species derived from 3,3,6,6,9,9-hexamethyl
      3,4,8,9-tetrahydro-1H-1,4,8,11-benzotetraazacyclotridecine-2,5,7,10(6H,11H)
      tetraone) react rapidly with O(2) in CH(2)Cl(2) or other weakly coordinating
      solvents to produce black mu-oxo-bridged diiron(IV) complexes, 2, in high yields.
      Complexes 2 have been characterized by X-ray crystallography (2 cases),
      microanalytical data, mass spectrometry, UV/Vis, Mossbauer, and (1)H NMR
      spectroscopies. Mossbauer data show that the diamagnetic Fe-O-Fe unit contains
      antiferromagnetically coupled S = 1 Fe(IV) sites; diamagnetic (1)H NMR spectra
      are observed. The oxidation of PPh(3) to OPPh(3) by 2 was confirmed by UV/Vis and
      GC-MS. Labeling experiments with (18)O(2) and H(2)(18)O established that the
      bridging oxygen atom of 2 derives from O(2). Complexes 2 catalyze the selective
      oxidation of benzylic alcohols into the corresponding aldehydes and bleach
      rapidly organic dyes, such as Orange II in MeCN-H(2)O mixtures; reactivity
      evidence suggests that free radical autoxidation is not involved. This work
      highlights a promising development for the advancement of green oxidation
      technology, as O(2) is an abundant, clean, and inexpensive oxidizing agent.

PMID- 15725006
TI  - Covalently attached monolayers on crystalline hydrogen-terminated silicon:
      extremely mild attachment by visible light.
AB  - A very mild method was developed for the attachment of high-quality organic
      monolayers on crystalline silicon surfaces. By using visible light sources, from
      447 to 658 nm, a variety of 1-alkenes and 1-alkynes were attached to hydrogen
      terminated Si(100) and Si(111) surfaces at room temperature. The presence and the
      quality of the monolayers were evaluated by static water contact angles, X-ray
      photoelectron spectroscopy, and IR spectroscopy. Monolayers prepared by thermal,
      UV light, or visible light initiation were compared. Additionally, the ability of
      infrared reflection-absorption spectroscopy to study organic monolayers on
      silicon was explored. A reaction mechanism is discussed on the basis of
      investigations of the reaction behavior of 1-alkenes with silicon wafers with
      varying types and levels of doping. Finally, a series of mixed monolayers derived
      from the mixed solutions of a 1-alkene and an omega-fluoro-1-alkene were
      investigated to reveal that the composition of the mixed monolayers was directly
      proportional to the molar ratio of the two compounds in the solutions.

PMID- 15725007
TI  - Amine-assisted facetted etching of CdSe nanocrystals.
AB  - The treatment of CdSe nanocrystals (NCs) in a 3-amino-1-propanol (APOL)/water
      (v/v = 10:1) mixture at 80 degrees C in the presence of O(2) causes them to
      undergo a slow chemical etching process, as evidenced by spectroscopic and
      structural investigations. Instead of the continuous blue shift expected from a
      gradual decrease in NC dimensions, a bottleneck behavior was observed with
      distinct plateaus in the peak position of photoluminescence (PL) and
      corresponding maxima in PL quantum yield (i.e., 34 +/-7%). It is presently argued
      that such etching behavior is a result of two competitive processes taking place
      on the surface of these CdSe NCs: (i) oxidation of the exposed Se-sites to acidic
      SeO(x)() entities, which are readily solubilized in the basic APOL/H(2)O mixture,
      and (ii) coordination of the underlying Cd-sites with both amines and hydroxyl
      moieties to temporally impede NC dissolution. This is consistent with the HRTEM
      results, which suggest that the etched NCs adopt pyramidal morphologies with Cd
      terminated facets (i.e., (0001) bases and either {011} or {21} sides) and account
      for the apparent resistance to etching at the plateau regions.

PMID- 15725008
TI  - Nanoscale vibrational analysis of single-walled carbon nanotubes.
AB  - We use near-field Raman imaging and spectroscopy to study localized vibrational
      modes along individual, single-walled carbon nanotubes (SWNTs) with a spatial
      resolution of 10-20 nm. Our approach relies on the enhanced field near a laser
      irradiated gold tip which acts as the Raman excitation source. We find that for
      arc-discharge SWNTs, both the radial breathing mode (RBM) and intermediate
      frequency mode (IFM) are highly localized. We attribute such localization to
      local changes in the tube structure (n, m). In comparison, we observe no such
      localization of the Raman active modes in SWNTs grown by chemical vapor
      deposition (CVD). The direct comparison between arc-discharge and CVD-grown tubes
      allows us to rule out any artifacts induced by the supporting substrate.

PMID- 15725009
TI  - Rhodium boryl complexes in the catalytic, terminal functionalization of alkanes.
AB  - A series of studies have been conducted by experimental and theoretical methods
      on the synthesis, structures, and reactions of CpRh boryl complexes that are
      likely intermediates in the rhodium-catalyzed regioselective, terminal
      functionalization of alkanes. The photochemical reaction of CpRh(eta(6)
      C(6)Me(6)) with pinacolborane (HBpin) generates the bisboryl complex
      CpRh(H)(2)(Bpin)(2) (2), which reacts with neat HBpin to generate
      CpRh(H)(Bpin)(3) (3). X-ray diffraction, density functional theory (DFT)
      calculations, and NMR spectroscopy suggest a weak, but measurable, B-H bonding
      interaction. Both 2 and 3 dissociate HBpin and coordinate PEt(3) or P(p-Tol)(3)
      to generate the conventional rhodium(III) species CpRh(PEt(3))(H)(Bpin) (4) and
      CpRh[P(p-tol)(3)](Bpin)(2) (5). Compounds 2 and 3 also react with alkanes and
      arenes to form alkyl- and arylboronate esters at temperatures similar to or below
      those of the catalytic borylation of alkanes and arenes. Further, these compounds
      were observed directly in catalytic reactions. The enthalpies and free energies
      for generation of the 16-electron intermediate and for the C-H bond cleavage and
      B-C bond formation have been calculated with DFT. These results strongly suggest
      that the C-H bond cleavage process occurs by a metal-assisted sigma-bond
      metathesis mechanism to generate a borane complex that isomerizes if necessary to
      place the alkyl group cis to the boryl group. This complex with cis boryl and
      alkyl groups then undergoes B-C bond formation by a second sigma-bond metathesis
      to generate the final functionalized product.

PMID- 15725010
TI  - Temperature-induced switching of the mechanism for intramolecular energy transfer
      in a 2,2':6',2' '-Terpyridine-based Ru(II)-Os(II) trinuclear array.
AB  - The synthesis and photophysical properties of a linear 2,2':6',2' '-terpyridine
      based trinuclear Ru(II)-Os(II) nanometer-sized array are described. This array
      comprises two bis(2,2':6',2' '-terpyridine) ruthenium(II) terminals connected via
      alkoxy-strapped 4,4'-diethynylated biphenylene units to a central bis(2,2':6',2'
      '-terpyridine) osmium(II) core. The mixed-metal linear array was prepared using
      the "synthesis at metal" approach, and the Ru(II)-Ru(II) separation is ca. 50 A.
      Energy transfer occurs with high efficiency from the Ru(II) units to the Os(II)
      center at all temperatures. Forster-type energy transfer prevails in a glassy
      matrix at very low temperature, but this is augmented by Dexter-type electron
      exchange at higher temperatures. This latter process, which is weakly activated,
      involves long-range superexchange interactions between the metal centers. In
      fluid solution, a strongly activated process provides for fast energy transfer.
      Here, a charge-transfer (CT) state localized on the bridge is populated as an
      intermediate species. The CT triplet does not undergo direct charge recombination
      to form the ground state but transfers energy, possibly via a second CT state, to
      the Os(II)-based acceptor. The short tethering strap constrains the geometry of
      the linker, especially in a glassy matrix, such that low-temperature electron
      exchange occurs across a particular torsion angle of 37 degrees . The probability
      of triplet energy transfer depends on temperature but always exceeds 75%.

PMID- 15725011
TI  - A ferroelectrically switchable columnar liquid crystal phase with achiral
      molecules: superstructures and properties of liquid crystalline ureas.
AB  - Novel columnar liquid crystalline compounds N,N'-bis(3,4,5-trialkoxylphenyl)ureas
      1a-c (R = n-C(8)H(17), n-C(12)H(25), and n-C(16)H(33)) were synthesized, and
      their phase transitions were measured by differential scanning calorimetery. The
      superstructures were investigated by X-ray diffraction, polarized light optical
      microscopy, and IR spectroscopy. The compounds exhibited both rectangular and
      hexagonal columnar phases in which the urea molecules in each column were stacked
      in one direction with strong hydrogen bonds. To confirm the ferroelectric
      switching, optoelectronic experiments were carried out, and the hexagonal
      columnar phases of 1b and 1c gave a sharp peak of spontaneous polarization in
      response to an applied triangular wave electric field (0.1-18 Hz). This is the
      first example of ferroelectrically switchable columnar liquid crystal phases
      generated by achiral molecules.

PMID- 15725012
TI  - Shape of 4S- and 4R-hydroxyproline in gas phase.
AB  - The alpha-amino acids 4(S)-hydroxyproline and 4(R)-hydroxyproline have been
      studied under isolation conditions in gas phase using laser-ablation molecular
      beam Fourier transform microwave spectroscopy. Two conformers of each molecule
      have been detected in the jet-cooled rotational spectrum. The most stable
      conformer in both molecules exhibits an intramolecular N...H-O hydrogen bond
      (configuration 1) between the hydrogen atom of the carboxylic group and the
      nitrogen atom. The second conformer is characterized by an intramolecular N
      H...O=C hydrogen bond (configuration 2). The conformers of 4(R)-hydroxyproline
      adopt a C(gamma)-exo puckering, while those of 4(S)-hydroxyproline present a
      C(gamma)-endo ring conformation. These ring conformations, which show the same
      propensity observed in collagen-like peptides, are stabilized by additional
      intramolecular hydrogen bonds involving the 4-hydroxyl group, with the exception
      of the most stable form of 4(S)-hydroxyproline for which a n-pi interaction
      between the oxygen atom of the 4-hydroxyl group and the carboxyl group carbon
      seems to be established. A gauche effect could be also contributing to stabilize
      the observed conformers.

PMID- 15725013
TI  - Simulation of the embryonic stage of ZnS formation from aqueous solution.
AB  - We investigate the processes of cluster formation and growth of ZnS from aqueous
      solution using molecular dynamics simulation techniques. The influence of both
      temperature and concentration is studied. We show that, at lower temperatures,
      the crucial process is the transformation of an outer-sphere Zn/S complex to an
      inner-sphere ion pair. Further growth of the latter is fast to generate
      negatively charged planar clusters. These clusters interact to form more stable,
      closed structures, which are found to be the global minima configurations in
      vacuo. At higher temperatures, no outer-sphere ion pairs are formed, and the
      larger cluster configurations form much more quickly.

PMID- 15725014
TI  - Understanding structure and bonding in early actinide 6d(0)5f0 MX6q (M = Th-Np; X
      = H, F) complexes in comparison with their transition metal 5d0 analogues.
AB  - The relationship between structure and bonding in actinide 6d(0)5f(0) MX(6)(q)()
      complexes (M = Th, Pa, U, Np; X = H, F; q = -2,-1, 0, +1) has been studied, based
      on density functional calculations with accurate relativistic actinide
      pseudopotentials. The detailed comparison of these prototype systems with their
      5d(0) transition metal analogues (M = Hf, Ta, W, Re) reveals in detail how the 5f
      orbitals modify the structural preferences of the actinide complexes relative to
      the transition metal systems. Natural bond orbital analyses on the hydride
      complexes indicate that 5f orbital involvement in sigma-bonding favors classical
      structures based on the octahedron, while d orbital contributions to sigma
      bonding favor symmetry lowering. The respective roles of f and d orbitals are
      reversed in the case of pi-bonding, as shown for the fluoride complexes.

PMID- 15725015
TI  - Flexible docking in solution using metadynamics.
AB  - We apply our recently developed metadynamics method to the docking of ligands on
      flexible receptors in water solution. This method mimics the real dynamics of a
      ligand exiting or entering an enzyme and in so doing reconstructs the free energy
      surface. We apply it to four docking cases: beta-trypsin/benzamidine, beta
      trypsin/chlorobenzamidine, immunoglobulin McPC-603/phosphocholine, and cyclin
      dependent kinase 2/staurosporine. In every case studied, the method is able to
      predict the docked geometry and the free energy of docking. Its added value with
      respect to many other available methods is that it reconstructs the complete free
      energy surface, including all the relevant minima and the barriers between them.

PMID- 15725016
TI  - Balancing dynamic and nondynamic correlation for diradical and aromatic
      transition states: a renormalized coupled-cluster study of the cope rearrangement
      of 1,5-hexadiene.
AB  - Single-reference coupled-cluster calculations employing the completely
      renormalized CCSD(T) (CR-CCSD(T)) approach have been used to examine the
      mechanism of the Cope rearrangement of 1,5-hexadiene. In agreement with
      multireference perturbation theory, the CR-CCSD(T) method favors the concerted
      mechanism of the Cope rearrangement involving an aromatic transition state. The
      CCSD(T) approach, which is often regarded as the "gold standard" of electronic
      structure theory, seems to fail in this case, favoring pathways through diradical
      structures.

PMID- 15725017
TI  - Unexpectedly strong energy stabilization inside the hydrophobic core of small
      protein rubredoxin mediated by aromatic residues: correlated ab initio quantum
      chemical calculations.
AB  - The formation of a hydrophobic core of globular proteins is believed to be the
      consequence of exterior hydrophobic forces of entropic nature. This, together
      with the low occurrence of hydrogen bonds in the protein core, leads to the
      opinion that the energy contribution of core formation to protein folding and
      stability is negligible. We show that stabilization inside the hydrophobic core
      of a small protein, rubredoxin, determined by means of high-level correlated ab
      initio calculations (complete basis set limit of MP2 stabilization energy +
      CCSD(T) correction term), amounted to approximately 50 kcal/mol. These results
      clearly demonstrate strong attraction inside a hydrophobic core. This finding may
      lead to substantial changes in the current view of protein folding. We also point
      out the inability of the DFT/B3LYP method to describe a strong attraction between
      studied amino acids.

PMID- 15725018
TI  - New selective haloform-type reaction yielding 3-hydroxy-2,2-difluoroacids:
      theoretical study of the mechanism.
AB  - Experimental results of an unprecedented haloform-type reaction in which 4-alkyl
      4-hydroxy-3,3-difluoromethyl trifluoromethyl ketones undergo base-promoted
      selective cleavage of the CO-CF(3) bond, yielding 3-hydroxy-2,2-difluoroacids and
      fluoroform, are rationalized using DFT (B3LYP) calculations. The gas-phase
      addition of hydroxide ion to 1,1,1,3,3-pentafluoro-4-hydroxypentan-2-one (R) is
      found to be a barrierless process, yielding a tetrahedral intermediate (INT),
      involving a DeltaG(r)(298 K) of -61.4 kcal/mol. The CO-CF(3) bond cleavage in INT
      leads to a hydrogen-bonded [CH(3)CHOHCF(2)CO(2)H...CF(3)](-) complex by passage
      through a transition structure (TS1) with a DeltaG()(298 K) of 20.8 kcal/mol and
      a DeltaG(r)(298 K) of 9.8 kcal/mol. This complex undergoes a proton transfer
      between its components, yielding a hydrogen-bonded
      [CH(3)CHOHCF(2)CO(2)...CHF(3)](-) complex. This process has associated with it a
      DeltaG()(298 K) of only 3.1 kcal/mol and a DeltaG(r)(298 K) of -43.3 kcal/mol.
      The CO-CF(2) bond cleavage in INT leads to a hydrogen-bonded
      [CH(3)CHOHCF(2)...CF(3)CO(2)H](-) complex by passage through a transition
      structure (TS3) with a DeltaG()(298 K) of 29.2 kcal/mol and a DeltaG(r)(298 K) of
      25.1 kcal/mol. The lower energy barrier found for CO-CF(3) bond cleavage in INT
      is ascribed to the larger number of fluorine atoms stabilizing the negative
      charge accumulated on the CF(3) moiety of TS1, as compared to the number of
      fluorine atoms stabilizing the negative charge on the CH(3)CHOHCF(2) moiety of
      TS3. The solvent-induced effects on the two pathways, introduced within the SCRF
      formalism through PCM calculations, do not reverse the predicted preference of
      the CO-CF(3) over the CO-CF(2) bond cleavage of R in the gas phase.

PMID- 15725019
TI  - Photochemistry of 2-(1-naphthyl)-2H-azirines in matrixes and in solutions:
      wavelength-dependent C-C and C-N bond cleavage of the azirine ring.
AB  - The photochemistry of 3-methyl-2-(1-naphthyl)-2H-azirine (1a) was investigated by
      the direct observation of reactive intermediates in matrixes at 10 K and by the
      characterization of reaction products in solutions. As already reported, the
      photolysis of the azirine 1a with the short-wavelength light (>300 nm) caused the
      C-C bond cleavage of the 2H-azirine ring to produce the nitrile ylide 2. However,
      the products derived from the C-N bond cleavage were exclusively obtained in the
      irradiation of 1a with the long-wavelength light (366 nm) both in matrixes and in
      solutions. When 1a was irradiated in the presence of O(2) with the long
      wavelength light, acetonitrile oxide (6) was produced through the capture of the
      biradical 4 generated by the C-N bond cleavage of 1a with O(2). An introduction
      of a nitro group into the naphthyl ring of 1a resulted in an acceleration of the
      decomposition in the long-wavelength irradiation and an extension of the
      wavelength region where the products derived from the C-N bond cleavage were
      selectively obtained. On the basis of molecular orbital calculations with the
      INDO/S method, the reason for the wavelength-dependent selective C-C and C-N bond
      cleavage of the azirine ring of 1a is discussed.

PMID- 15725020
TI  - Altering the folding patterns of naphthyl trimers.
AB  - Proteins can adopt helical and sheet-type secondary structures that depend on
      their primary sequence of amino acids. Nonnatural foldamers have been developed
      to emulate these protein structures as well as investigate various types of
      noncovalent interactions. Here we report a strategy to access two distinct
      folding topologies in aqueous solutions using the inherent recognition properties
      of aromatic donor/acceptor interactions. These oligomers are constructed of
      electron-rich 1,5-dialkoxynaphthalene (Dan) and electron-deficient 1,4,5,8
      naphthalenetetracarboxylic diimide (Ndi) units. A trimer of the sequence Dan-Ndi
      Dan was shown to adopt a pleated fold in solution, while its constitutional
      isomer, Dan-Dan-Ndi, adopted an intercalative or turn-type fold. UV-vis and NOESY
      spectroscopy analyses were consistent with the two different conformations. This
      study illustrates the designability of folding naphthyl oligomers and encourages
      the use of directed aromatic interactions to construct larger and more complex
      assemblies in water.

PMID- 15725021
TI  - Kinetics of the reactions of halide anions with carbocations: quantitative energy
      profiles for s(n)1 reactions.
AB  - Rate constants for the reactions of Laser flash photolytically generated
      benzhydrylium ions (diarylcarbenium ions) with halide ions have been determined
      in various solvents, including neat and aqueous acetonitrile as well as some
      alcohols. Substitution of the rate constants into the correlation equation log k
      = s(N + E) yields the nucleophilicity parameters N for the halide ions in
      different solvents. Linear correlations with negative slopes are found between
      the nucleophilicity parameters N for Cl(-) and Br(-) in different solvents and
      the solvent ionizing powers Y of the corresponding solvents. Increasing halide
      solvation reduces the rates of carbocation/chloride combinations by approximately
      half as much as it increases the rates of ionizations of benzhydryl chlorides.
      Comparison of the solvent dependent nucleophilicity parameters N of halide anions
      and the nucleophilicity parameters N(1) for solvents yields a quantitative
      prediction of common ion rate depression, as demonstrated by the analysis of a
      variety of literature reported mass-law constants alpha. Combination of the rate
      constants for the reactions of benzhydrylium ions with halide ions (k(-)()(1))
      reported in this work with the ionization constants of benzhydryl halides (k(1))
      and the recently reported rate constants for the reactions of benzhydrylium ions
      with solvents (k(2)) yields complete quantitative free energy profiles for
      solvolysis reactions. The applicability of Hammond's postulate for interpreting
      solvolysis reactions can thus be examined quantitatively.

PMID- 15725022
TI  - Enantioselective, chirally templated sol-gel thin films.
AB  - Enantioselective surfactant-templated thin films were fabricated through the sol
      gel (SG) process. The enantioselectivity is general in the sense that it
      discriminates between pairs of enantiomers not used for the imprinting process.
      The chiral cationic surfactant (-)-N-dodecyl-N-methylephedrinium bromide (1) was
      used as the surfactant template, and after its extraction chiral domains were
      created. The chiral discriminative feature of these films was examined by
      challenging with pure enantiomer solutions for rebinding. Selective adsorption
      was shown using (R)- and (S)-propranolol, (R)-2 and (S)-2, respectively, and (R)-
      and (S)-2,2,2-trifluoro-1-(9-anthryl)ethanol, (R)-3 and (S)-3, respectively, as
      the chiral probes. The selective adsorption was measured by fluorescence
      analysis, and the chiral selectivity factors were found to be 1.6 for 2 and 2.25
      for 3. In both cases, (R)-enantiomer was adsorbed preferably. The resulting
      material was characterized by transmission electron microscopy, by diffraction,
      and by surface area measurements, and was found to be semicrystalline with short
      range ordered domains (50 A) of hexagonal symmetry.

PMID- 15725023
TI  - Multiply doped nanostructured silicate sol-gel thin films: spatial segregation of
      dopants, energy transfer, and distance measurements.
AB  - Physical and chemical strategies that place designed molecules in spatially
      separated regions of surfactant-templated mesostructured silicate thin films are
      used to prepare films containing rhodamine 6G (R6G), lanthanide complexes, and
      both simultaneously. Fluorescence and photoexcitation spectra of R6G in amorphous
      and structured thin films show that it is located inside the surfactant micelles
      of structured thin films. A silylated ligand that binds lanthanides condenses to
      form part of the silica framework and causes the lanthanide to localize in the
      silica. Luminescence and photoexcitation spectra show that energy transfer from
      the metal complex to R6G occurs in the films. R6G quenches Tb emission in a
      concentration-dependent manner. Energy transfer efficiency is calculated using
      the Tb luminescence lifetime, and this quantity is used to calculate the distance
      between Tb and R6G with the aid of Forster theory.

PMID- 15725024
TI  - Polyynes as a model for carbyne: synthesis, physical properties, and nonlinear
      optical response.
AB  - With the Fritsch-Buttenberg-Wiechell rearrangement as a primary synthetic route,
      a series of conjugated, triisopropylsilyl end-capped polyynes containing 2-10
      acetylene units has been assembled. In a few steps, significant quantities of the
      polyynes are made available, which allow for a thorough analysis of their
      structural, physical, and optical properties. Molecules in the series have been
      characterized in detail using (13)C NMR spectroscopy, differential scanning
      calorimetry, mass spectrometry, and, for four derivatives including octayne 6, X
      ray crystallography. UV-vis spectroscopy of the polyynes 1-7 shows a consistent
      lowering of the HOMO-LUMO gap (E(g)) as a function of the number of acetylene
      units (n), fitting a power-law relationship of E(g) approximately n(-)(0.379)(+/
      )(0.002). The third-order nonlinear optical (NLO) properties of the polyyne
      series have been examined, and the nonresonant molecular second
      hyperpolarizabilities (gamma) increase as a function of length according to the
      power-law gamma approximately n(4.28)(+/-)(0.13). This result exhibits an
      exponent that is larger than theoretically predicted for polyynes and higher than
      is observed for polyenes and polyenynes. The combined linear and nonlinear
      optical results confirm recent theoretical studies that suggest polyynes as model
      1-D conjugated systems. On the basis of UV-vis spectroscopic analysis, the
      effective conjugation length for this series of polyynes is estimated to be ca. n
      = 32, providing insight into characteristics of carbyne.

PMID- 15725025
TI  - Elucidation of the thermochemical properties of triphenyl- or tributyl
      substituted Si-, Ge-, and Sn-centered radicals by means of electrochemical
      approaches and computations.
AB  - Redox potentials of a number of triphenyl- or tributyl-substituted Si-, Ge-, or
      Sn-centered radicals, R(3)M(*), have been measured in acetonitrile,
      tetrahydrofuran, or dimethyl sulfoxide by photomodulated voltammetry or through a
      study of the oxidation process of the corresponding anions in linear sweep
      voltammetry. For the results pertaining to the Ph(3)M(*) series (including
      literature data for M = C), the order of reduction potentials follows Sn > Ge > C
      > Si, while for the two oxidation potentials, it is C > Si. The effect of the R
      group on the redox properties of R(3)Sn(*) is pronounced in that the reduction
      potential is more negative by 490 mV in tetrahydrofuran (390 mV in dimethyl
      sulfoxide) when R is a butyl rather than a phenyl group. The experimental trends
      have been substantiated through quantum chemical calculations, and they can be
      explained qualitatively by considering a combination of effects, such as charge
      capacity being most pronounced for the heavier elements, resonance stabilization
      present for the planar Ph(3)C(*) and all R(3)M(+)(), and finally a contribution
      from solvation. The solvation of R(3)M(-) is observed to be relatively strong
      because of a rather localized negative charge in the pyramidal geometry. However,
      there is no evidence in the calculations to support the existence of covalent
      interactions between solvent and anions. The solvation of R(3)M(+)() is
      relatively weak, which may be attributed to the planar geometry around the center
      atom, leading to more spread out charge than that for a pyramidal geometry.
      Although the calculated solvation energies based on the polarizable continuum
      model approach exhibit the expected trends, they are not able to reproduce the
      experimentally derived values on a detailed level for these types of ions. An
      evaluation of the general performance of the continuum model is provided on the
      basis of present and previous studies.

PMID- 15725026
TI  - Mechanistic investigation of the staudinger ligation.
AB  - The Staudinger ligation of azides and phosphines has found widespread use in the
      field of chemical biology, but the mechanism of the transformation has not been
      characterized in detail. In this work, we undertook a mechanistic study of the
      Staudinger ligation with a focus on factors that affect reaction kinetics and on
      the identification of intermediates. The Staudinger ligation with alkyl azides
      was second-order overall and proceeded more rapidly in polar, protic solvents.
      Hammett analyses demonstrated that electron-donating substituents on the
      phosphine accelerate the overall reaction. The electronic and steric properties
      of the ester had no significant impact on the overall rate but did affect product
      ratios. Finally, the structure of an intermediate that accumulates under
      anhydrous conditions was identified. These findings establish a platform for
      optimizing the Staudinger ligation for expanded use in biological applications.

PMID- 15725027
TI  - Determination of N-NO bond dissociation energies of N-methyl-N
      nitrosobenzenesulfonamides in acetonitrile and application in the mechanism
      analyses on NO transfer.
AB  - The heterolytic and homolytic N-NO bond dissociation energies of seven
      substituted N-methyl-N-nitrosobenzenesulfonamides (abbreviated as G-MNBS, G = p
      OCH(3), p-CH(3), p-H, p-Cl, p-Br, 2,5-2Cl, m-NO(2)) in acetonitrile solution were
      evaluated for the first time by using titration calorimetry and relative
      thermodynamic cycles according to Hess' law. The results show that the energetic
      scales of the heterolytic and homolytic N-NO bond dissociation energies of G-MNBS
      in acetonitrile solution cover the ranges from 44.3 to 49.5 and from 33.0 to 34.9
      kcal/mol for the neutral G-MNBS, respectively, which indicates that N-methyl-N
      nitrosobenzenesulfonamides are much easier to release a NO radical (NO(*)) than
      to release a NO cation (NO(+)). The estimation of the heterolytic and homolytic
      (N-NO)(-)(*) bond dissociation energies of the seven G-MNBS radical anions in
      acetonitrile solution gives the energetic ranges of -15.8 to -12.9 and -3.1 to
      1.8 kcal/mol for the (N-NO)(-)(*) bond homolysis and heterolysis, respectively,
      which means that G-MNBS radical anions are very unstable at room temperature and
      able to spontaneously or easily release a NO radical or NO anion (NO(-)), but
      releasing a NO radical is easier than releasing NO anion. These determined N-NO
      bond dissociation energies of G-MNBS and their radical anions have been
      successfully used in the mechanism analyses of NO transfer from G-MNBS to 3,6
      dibromocarbazole and the reactions of NO with the substituted N-methyl
      benzenesulfonamide nitranions (G-MBSN(-)) in acetonitrile solution.

PMID- 15725028
TI  - Generation and reaction of tungsten-containing carbonyl ylides: [3 + 2]
      cycloaddition reaction with electron-rich alkenes.
AB  - Novel tungsten-containing carbonyl ylides 7, generated by the reaction of the o
      alkynylphenyl carbonyl derivatives 1 with a catalytic amount of W(CO)(5)(thf),
      reacted with alkenes to give polycyclic compounds 5 through [3 + 2]-cycloaddition
      reaction followed by intramolecular C-H insertion of the produced nonstabilized
      carbene complex intermediates 8. In the presence of triethylsilane, these
      tungsten-containing carbene intermediates 8 were smoothly trapped
      intermolecularly by triethylsilane to give silicon-containing cycloadducts 17
      with regeneration of the W(CO)(5) species. By this procedure, the scope of
      alkenes employable for this reaction was clarified. The presence of the tungsten
      containing carbonyl ylide 7c was confirmed by direct observation of the mixture
      of o-ethynylphenyl ketone 1c and W(CO)(5)(thf-d(8)). Careful analysis of the
      intermediate by 2D NMR, along with the observation of the direct coupling with
      tungsten-183 employing the (13)C-labeled substrate, confirmed the structure of
      the ylide 7c. Examination using (E)- or (Z)- vinyl ether revealed that the [3 +
      2]-cycloaddition reaction proceeded in a concerted manner and that the facial
      selectivity of the reaction differed considerably depending on the presence or
      absence of triethylsilane. These results clarified the reversible nature of this
      [3 + 2]-cycloaddition reaction.

PMID- 15725029
TI  - Photochromic control of photoinduced electron transfer. Molecular double-throw
      switch.
AB  - A molecular double-throw switch that employs a photochromic moiety to direct
      photoinduced electron transfer from an excited state donor down either of two
      pathways has been prepared. The molecular triad consists of a free base porphyrin
      (P) linked to both a C(60) electron acceptor and a dihydroindolizine (DHI)
      photochrome. Excitation of the porphyrin moiety of DHI-P-C(60) results in
      photoinduced electron transfer with a time constant of 2.3 ns to give the DHI
      P(*)(+)-C(60)(*)(-) charge-separated state with a quantum yield of 82%. UV (366
      nm) light photoisomerizes the DHI moiety to the betaine (BT) form, which has a
      higher reduction potential than DHI. Excitation of the porphyrin of BT-P-C(60) is
      followed by photoinduced electron transfer with a time constant of 56 ps to
      produce BT(*)(-)-P(*)(+)-C(60) in 99% yield. Isomerization of BT-P-C(60) back to
      DHI-P-C(60) may be achieved with visible light, or thermally. Thus, photoinduced
      charge separation originating from the porphyrin is reversibly directed down
      either of two different pathways by photoisomerization of the dihydroindolizine.
      The switch may be cycled many times.

PMID- 15725030
TI  - Asymmetric synthesis of dihydrofurans via a formal retro-Claisen
      photorearrangement.
AB  - Solution-phase irradiation of a series of syn-7-benzoylnorbornene derivatives is
      shown to lead to cis-fused dihydrofuran derivatives in low quantum but excellent
      chemical yields in what is formally a retro-Claisen rearrangement. In analogy to
      the well-known Paterno-Buchi reaction, the first step of the rearrangement is
      suggested to involve (n,pi)(3)-mediated addition of the carbonyl oxygen to the
      norbornene double bond, producing a triplet 1,4-biradical. This intermediate,
      rather than closing to the oxetane, undergoes cleavage accompanied by intersystem
      crossing to form the dihydrofuran. To determine whether the retro-Claisen
      photorearrangement could be carried out enantioselectively, the 7
      benzoylnorbornene reactant was equipped with a para-carboxylic acid substituent
      to which a series of optically pure amines was attached ionically via salt
      bridges. Irradiation of these salts in the crystalline state followed by
      diazomethane workup (the solid-state ionic chiral auxiliary method) was shown to
      afford the corresponding dihydrofuran in optical yields as high as 93% at 95%
      conversion. X-ray crystallography revealed that the enantioselectivity arises
      from crystallization of the reactant in a conformation in which the carbonyl
      oxygen is more favorably oriented for bond formation to one end of the norbornene
      double bond than the other, thus leading to a predominance of a single
      enantiomer.

PMID- 15725031
TI  - Probing the local environments of phosphorus in aluminophosphate-based
      mesostructured lamellar materials by solid-state NMR spectroscopy.
AB  - We have characterized a series of mesostructured aluminophosphate (AlPO)-based
      lamellar materials by several solid-state NMR techniques. In particular, we were
      able to estimate the average number of Al atoms and identify the nature of other
      ancillary groups in the second coordination sphere for each P site. Our work has
      shown that a combination of several dipolar coupling-based (31)P/(27)Al double
      resonance techniques such as transfer of population in double-resonance
      (TRAPDOR), rotational echo double-resonance (REDOR), and heteronuclear
      correlation spectroscopy (HETCOR) as well as (1)H --> (31)P cross polarization
      (CP) can provide more detailed structural information regarding the local
      environments of P and Al atoms in AlPO-based mesostructured materials, which is
      not readily available from straightforward (31)P and (27)Al magic-angle spinning
      (MAS) experiments.

PMID- 15725032
TI  - Development of a technique to determine bicyclomycin-rho binding and
      stoichiometry by isothermal titration calorimetry and mass spectrometry.
AB  - Bicyclomycin (1) is the only natural product inhibitor of the transcription
      termination factor rho. Rho is a hexameric helicase that terminates nascent RNA
      transcripts utilizing ATP hydrolysis and is an essential protein for many
      bacteria. The paucity of information concerning the 1-rho interaction stems from
      the weak binding affinity of 1. We report a novel technique using imine formation
      with rho to enhance the affinity of a bicyclomycin analogue and determine the
      binding stoichiometry by isothermal titration calorimetry (ITC) and mass
      spectrometry (MS). Our designed bicyclomycin ligand, 5a-(3-formyl-phenylsulfanyl)
      dihydrobicyclomycin (2) (apparent I(50) = 4 muM), inhibits rho an order of
      magnitude more efficiently than 1 (I(50) = 60 muM). MS shows that 2 selectively
      forms an imine with K181 in rho. We found that despite the heterogeneity of ATP
      binding (three tight and three weak) imposed on the rho hexamer, the nearby
      bicyclomycin binding pocket is not affected, and both 1 and 2 bind with equal
      affinity to all six subunits.

PMID- 15725033
TI  - Does core size matter in the kinetics of ligand exchanges of monolayer-protected
      Au clusters?
AB  - This paper compares the kinetics of exchanges of phenylethanethiolate ligands
      (PhC2S-) of the monolayer-protected clusters (MPCs) Au(38)(SC2Ph)(24) and
      Au(140)(SC2Ph)(53) with p-substituted arylthiols (p-X-PhSH), where X = NO(2), Br,
      CH(3), OCH(3), and OH. First-order rate constants at 293 K for exchange of the
      first ca. 25% of the ligands on the molecule-like Au(38)(SC2Ph)(24) MPC, measured
      using (1)H NMR, vary linearly with the in-coming arythiol concentration; ligand
      exchange is an overall second-order reaction. Remarkably, the second-order rate
      constants for ligand exchange on Au(38)(SC2Ph)(24) are very close to those of
      corresponding exchange reactions on the larger nanoparticle Au(140)(SC2Ph)(53)
      MPCs. These are the first results that quantitatively show that the chemical
      reactivity of different sized nanocrystals is almost independent of size;
      presumably, this is because the locus of the initial ligand exchanges is a common
      kind of site, thought to be the nanocrystal vertexes. The rates of later stages
      of exchange (beyond ca. 25%) differ for Au(38) and Au(140) cores, the latter
      being much slower presumably due to its larger terrace-like surface atom content.
      The reverse exchange reaction was studied for Au(38)(p-X-arylthiolate)(24) MPCs
      (X = NO(2), Br, and CH(3)), where the in-coming ligand is now phenylethanethiol.
      Remarkably, the rate constants of both forward and reverse exchanges display
      identical substituent effects, which implies a concurrent bonding of both in
      coming and leaving ligands to the Au core in the rate-determining step, as in an
      associative mechanism. X = NO(2) gives the fastest rates, and the ratio of
      forward and reverse rate constants gives an equilibrium constant of K(EQ,PE) =
      4.0 that is independent of X.

PMID- 15725034
TI  - Systematic study of the structure-property relationship of a series of ferrocenyl
      nonlinear optical chromophores.
AB  - A series of novel nonlinear optical (NLO) chromophores 1-4 incorporating the
      ferrocenyl (Fc) group as an electron donor and 2-dicyanomethylene-3-cyano-4
      methyl-2,5-dihydrofuran (TCF) derivatives as electron acceptors are presented.
      The use of a constant Fc donor and varied acceptors and bridges makes it possible
      to systematically determine the contribution of the conjugated bridge and the
      acceptor strength to chromophore nonlinear optical activity. The X-ray crystal
      structures of all four chromophores allow for the systematic investigation of the
      structure-property relationship for this class of molecules. For example, the
      crystal structures reveal that both cyclopentadienyl groups in the ferrocenyl
      donor contribute to the electron donating ability. The first-order
      hyperpolarizabilities beta of these chromophores, measured by hyper-Rayleigh
      scattering (HRS) relative to p-nitroaniline are reported. These beta values are
      compared to those calculated by density functional theory (DFT). The excellent
      agreement between the theoretical and experimental beta values demonstrates that
      a linear relation exists between the hyperpolarizability and the bond length
      alternation. An electrooptic coefficient, r(33), of approximately 25 pm/V at 1300
      nm, for compound 4, incorporated into a polymer matrix, is competitive with
      organic chromophores. Moreover, this r(33) is more than 30 times larger than the
      previously reported value for an organometallic chromophore in a poled polymer
      matrix. This work not only underscores the potential for Fc donor moieties, which
      have been underutilized, but also demonstrates that experimental characterization
      and theoretical simulations are now congruent, viable methods for assessing
      potential performance of NLO materials.

PMID- 15725035
TI  - High-resolution four-dimensional 1H-13C NOE spectroscopy using methyl-TROSY,
      sparse data acquisition, and multidimensional decomposition.
AB  - An approach for recording four-dimensional (4D) methyl (1)H-(13)C-(13)C-(1)H
      NOESY spectra with high resolution and sensitivity is presented and applied to
      Malate Synthase G (723 residues, 82 kDa). Sensitivity and resolution have been
      optimized using a highly deuterated, methyl-protonated sample in concert with
      methyl-TROSY, sparse data sampling in the three indirect dimensions, and 4D
      spectral reconstruction using multidimensional decomposition (MDD). A sparse data
      acquisition protocol is introduced that ensures that sufficiently long indirect
      acquisition times can be employed to exploit the decreased relaxation rates
      associated with methyl-TROSY, without increasing the duration of the 4D
      experiment beyond acceptable measurement times. In this manner, only a fraction (
      approximately 30%) of the experimental data that would normally be needed to
      achieve a spectrum of high resolution is acquired. The reconstructed 4D spectrum
      is of similar resolution and sensitivity to three-dimensional (3D) (13)C-edited
      NOE spectra, is straightforward to analyze, and resolves ambiguities that emerge
      when 3D data sets only are considered.

PMID- 15725036
TI  - A quantum chemical study of the reaction mechanism of acetyl-coenzyme a synthase.
AB  - Recent experimental and theoretical studies have focused on the mechanism of the
      A-cluster active site of acetyl-CoA synthase that produces acetyl-CoA from a
      methyl group, carbon monoxide, and CoA. Several proposals have been made
      concerning the redox states of the (Ni-Ni) bimetallic center and the iron-sulfur
      cluster connected to one of the metals. Using hybrid density functional theory,
      we have investigated putative intermediate states from the catalytic cycle. Among
      our conclusions are the following: (i) the zerovalent state proposed for the
      proximal metal is unlikely if the charge on the iron-sulfur cluster is +2; (ii) a
      mononuclear mechanism in which both CO and CH(3) bind the proximal nickel is
      favored over the binuclear mechanism in which CO and CH(3) bind the proximal and
      distal nickel ions, respectively; (iii) the formation of a disulfide bond in the
      active site could provide the two electrons necessary for the reaction but only
      if methylation occurs simultaneously; and (iv) the crystallographic closed form
      of the active site needs to open to accommodate ligands in the equatorial site.

PMID- 15725037
TI  - Intramolecular migration of amide hydrogens in protonated peptides upon
      collisional activation.
AB  - Presently different opinions exist as to the degree of scrambling of amide
      hydrogens in gaseous protonated peptides and proteins upon collisional activation
      in tandem mass spectrometry experiments. This unsettled controversy is not
      trivial, since only a very low degree of scrambling is tolerable if collision
      induced dissociation (CID) should provide reliable site-specific information from
      (1)H/(2)H exchange experiments. We have explored a series of unique,
      regioselectively deuterium-labeled peptides as model systems to probe for
      intramolecular amide hydrogen migration under low-energy collisional activation
      in an orthogonal quadrupole time-of-flight electrospray ionization (Q-TOF ESI)
      mass spectrometer. These peptides contain a C-terminal receptor-binding sequence
      and an N-terminal nonbinding region. When the peptides form a receptor complex,
      the amide hydrogens of the interacting sequences are protected against exchange
      with the solvent, while the amide hydrogens of the nonbinding sequences exchange
      rapidly with the solvent. We have utilized such long-lived complexes to generate
      peptides labeled with deuterium in either the binding or nonbinding region, and
      the expected regioselectivity of this labeling was confirmed after pepsin
      proteolysis. CID of such deuterated peptides, [M + 2H](2+), yielded fragment ions
      (b- and y-ions) having a deuterium content that resemble the theoretical values
      calculated for 100% scrambling. Thus, complete randomization of all hydrogen
      atoms attached to nitrogen and oxygen occurs in the gaseous peptide ion prior to
      its dissociation.

PMID- 15725038
TI  - Obstructive sleep apnea: what does the cardiovascular physician need to know?
AB  - Obstructive sleep apnea (OSA) is a common disorder in adults. It is becoming
      increasingly recognized as a risk factor for cardiovascular diseases such as
      hypertension, pulmonary hypertension, myocardial infarction, and stroke. Knowing
      the pathophysiologic effects that occur during obstructive apnea assists in
      understanding how chronic complications and sequelae develop. OSA is also being
      recognized as associated with glucose intolerance and motor vehicle accidents.
      Polysomnography in a sleep laboratory remains the diagnostic method of choice.
      Treatment options are somewhat limited in scope, but nasal continuous positive
      airway pressure is the first line and has been shown to clearly improve many of
      the symptoms and sequelae of the syndrome. Cardiovascular physicians require a
      working knowledge of OSA and its complications, as many of the diseases they
      manage have shown links to this sleep disorder.

PMID- 15725039
TI  - Management of diabetic dyslipidemia: need for reappraisal of the goals.
AB  - Cardiovascular disease is the leading cause of mortality among people with
      diabetes mellitus, accounting for 70% of all deaths. As the prevalence of
      diabetes increases significantly worldwide, greater attention must be focused on
      preventing cardiovascular events in this group. One contributor to this increased
      event rate is the characteristic pattern of dyslipidemia in diabetic patients,
      consisting of elevated serum triglyceride levels, decreased high-density
      lipoprotein levels, and an increased proportion of small, dense, low-density
      lipoproteins. Several pharmacologic agents have been used to treat this
      dyslipidemia including HMG-CoA reductase inhibitors, fibric acid derivatives,
      niacin (nicotinic acid), thiazolidinediones, and fish oils, as well as other non
      pharmacologic measures. Currently, the most extensive data for a reduction in
      cardiovascular events in patients with diabetes exist for HMG-CoA reductase
      inhibitors. The results of these trials indicate that HMG-CoA reductase inhibitor
      therapy should be considered for all patients with diabetes at sufficient risk
      for cardiovascular events, regardless of serum low-density lipoprotein
      cholesterol level. Several ongoing trials of various pharmacologic agents should
      help clarify the role of these agents alone and in combination with HMG-CoA
      reductase inhibitors in the management of diabetic dyslipidemia.

PMID- 15725040
TI  - Interventional cardiovascular pharmacotherapy: current issues.
AB  - In the last decade, a variety of novel anticoagulant and antiplatelet agents that
      improve outcomes in patients undergoing percutaneous coronary revascularization
      have emerged. During the next decade, continued refinements in catheter-based
      device technology should lead to further increases in the number of
      interventional procedures. The use of optimal antithrombotic strategies is
      pivotal in reducing adverse events among patients undergoing percutaneous
      coronary intervention (PCI). Our purpose is to review the current evidence
      regarding the efficacy of available adjunctive anticoagulant and antiplatelet
      agents in treating patients undergoing percutaneous coronary revascularization.
      It should be borne in mind that patients undergoing PCI in the midst of an acute
      coronary event require a different level of coagulation and platelet aggregation
      inhibition than low-risk patients undergoing elective PCI for stable angina
      pectoris. Similarly, generalizing antithrombotic regimen safety data to a wide
      spectrum of catheter-based therapeutic devices should be avoided. A level of
      anticoagulation that is safe and effective for angioplasty and stent placement
      may not be sufficient for devices with longer intracoronary dwell times such as
      brachytherapy catheters. In light of current evidence, activated clotting times
      should be targeted in the 200- to 250-second range during elective PCI and in the
      250- to 300-second range when intervening on a higher-risk lesion, such as one
      with an angiographically visible thrombus or in patients presenting with an acute
      coronary syndrome (ACS).Low-dose enoxaparin sodium is an attractive antithrombin
      strategy in PCI because it is intrinsically adjusted for renal function, age, and
      concomitant glycoprotein (GP) IIb/IIIa antagonist use. Other low-molecular weight
      heparins have also been studied as adjunctive anticoagulants during cardiac
      catheterization. For example, in pilot studies, dalteparin sodium was shown to
      have a good safety profile when used alone or in combination with abciximab
      during PCI.A wealth of data supports the use of a GP IIb/IIIa antagonist in
      patients presenting with ACS, especially those with high-risk features such as
      elevated cardiac markers; the systematic use of GP IIb/IIIa inhibitors in this
      population is therefore encouraged. Overall, the use of GP IIb/IIIa inhibitors
      reduces the incidence of thrombotic complications following PCI, is associated
      with a mortality benefit, but has no impact on the risk of restenosis.

PMID- 15725041
TI  - Bacterial pericarditis: diagnosis and management.
AB  - Bacterial pericarditis occurs by direct infection during trauma, thoracic
      surgery, or catheter drainage, by spread from an intrathoracic, myocardial, or
      subdiaphragmatic focus, and by hematogenous dissemination. The frequent causes
      are Staphylococcus and Streptococcus (rheumatic pancarditis), Haemophilus, and M.
      tuberculosis. In AIDS pericarditis, the incidence of bacterial infection is much
      higher than in the general population, with a high proportion of Mycobacterium
      avium-intracellulare infection. Purulent pericarditis is the most serious
      manifestation of bacterial pericarditis, characterized by gross pus in the
      pericardium or microscopically purulent effusion. It is an acute, fulminant
      illness with fever in virtually all patients. Chest pain is uncommon. Purulent
      pericarditis is always fatal if untreated. The mortality rate in treated patients
      is 40%, and death is mostly due to cardiac tamponade, systemic toxicity, cardiac
      decompensation, and constriction. Tuberculous infection may present as acute
      pericarditis, cardiac tamponade, silent (often large) relapsing pericardial
      effusion, effusive-constrictive pericarditis, toxic symptoms with persistent
      fever, and acute, subacute, or chronic constriction. The mortality in untreated
      patients approaches 85%. Urgent pericardial drainage, combined with intravenous
      antibacterial therapy (e.g. vancomycin 1g twice daily, ceftriaxone 1-2g twice
      daily, and ciprofloxacin 400 mg/day) is mandatory in purulent pericarditis.
      Irrigation with urokinase or streptokinase, using large catheters, may liquify
      the purulent exudate, but open surgical drainage is preferable. The initial
      treatment of tuberculous pericarditis should include isoniazid 300 mg/day,
      rifampin 600 mg/day, pyrazinamide 15-30 mg/kg/day, and ethambutol 15-25
      mg/kg/day. Prednisone 1-2 mg/kg/day is given for 5-7 days and progressively
      reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential.
      Pericardiectomy is reserved for recurrent effusions or continued elevation of
      central venous pressure after 4-6 weeks of antituberculous and corticosteroid
      therapy.

PMID- 15725042
TI  - Aortic insufficiency: defining the role of pharmacotherapy.
AB  - Major advances in the diagnostic, evaluation, and particularly surgical treatment
      of aortic regurgitation (AR) have redefined the role of medical treatment. In
      acute AR, aortic valve replacement (AVR) is the only life-saving treatment.
      Medical treatment may improve the hemodynamic state temporarily before surgery.
      Rationale of medical treatment in chronic AR is based on the natural history and
      pathophysiology of the disease. The primary goal is to optimize the time of the
      AVR. If there is any symptom and/or left ventricular (LV) dysfunction, early AVR
      is required. Vasodilators should only be considered as a short-term treatment
      before surgery if there is evidence of severe heart failure or as a long-term
      treatment if AVR is contraindicated because of cardiac or noncardiac factors. In
      asymptomatic patients with severe chronic AR and normal LV function (even if the
      left ventricle is moderately dilated), vasodilators may prolong the compensated
      phase of chronic AR, although proof of their efficacy in delaying AVR is limited.
      Nifedipine is the best evidence-based treatment in this indication. ACE
      inhibitors are particularly useful for hypertensive patients with AR. beta
      Adrenoceptor antagonists (beta-blockers) may be indicated to slow the rate of
      aortic dilatation and delay the need for surgery in patients with AR associated
      with aortic root disease. Furthermore, they may improve cardiac performance by
      reducing cardiac volume and LV mass in patients with impaired LV function after
      AVR for AR.

PMID- 15725043
TI  - Fondaparinux sodium compared with enoxaparin sodium: a cost-effectiveness
      analysis.
AB  - INTRODUCTION: Patients undergoing major orthopedic surgery face considerable risk
      of venous thromboembolism (VTE), which may be fatal unless they receive
      prophylactic treatment. Fondaparinux sodium is a new antithrombotic agent that is
      indicated for prophylaxis of VTE after major orthopedic surgery. This paper
      presents a cost-effectiveness analysis of fondaparinux sodium and enoxaparin
      sodium, the latter being the most commonly used agent for prophylaxis of VTE.
      METHODS: The analysis is based on an international simulation model, using
      Norwegian unit costs, and Norwegian data of 55 000 patients undergoing orthopedic
      surgery between 1999 and 2001. We estimated the expected incidence of VTE and VTE
      related deaths, and expected costs of VTE-related care for each of the two
      prophylactic agents for different periods. RESULTS AND CONCLUSION: The results
      indicate that fondaparinux sodium is likely to be more effective than enoxaparin
      sodium in preventing the incidence of VTE. By day 90, fondaparinux sodium is
      expected to avoid 180 more VTE events, and between 8 and 33 more VTE-related
      deaths per 10,000 patients than enoxaparin sodium. Fondaparinux sodium is also a
      cost-saving option in short follow-up periods for hip fracture surgery. For
      extended follow-up periods (i.e. 5 years), fondaparinux sodium is also likely to
      represent the lower cost treatment option after total knee and hip replacement.
      The sensitivity analyses show that the main results are robust to changes in the
      most important parameters. Results are, however, sensitive to the price
      difference between the two drugs.

PMID- 15725045
TI  - Emphysema in alpha1-antitrypsin deficiency: does replacement therapy affect
      outcome?
AB  - Severe alpha(1)-antitrypsin (AAT) deficiency is an inherited disorder that leads
      to the development of emphysema in smokers at a relatively young age; most are
      disabled in their forties. Emphysema is caused by the protease-antiprotease
      imbalance when smoking-induced release of neutrophil elastase in the lung is
      inadequately inhibited by the deficient levels of AAT, the major inhibitor of
      neutrophil elastase. This protease-antiprotease imbalance leads to proteolytic
      damage to lung connective tissue (primarily elastic fibers), and the development
      of panacinar emphysema. AAT replacement therapy, most often applied by weekly
      intravenous infusions of AAT purified from human plasma, has been used to
      partially correct the biochemical defect and raise the serum AAT level above a
      theoretically protective threshold level of 0.8 g/L. A randomized controlled
      clinical trial was not considered feasible when purified antitrypsin was released
      for clinical use. However, AAT replacement therapy has not yet been proven to be
      clinically effective in reducing the progression of disease in AAT-deficient
      patients. There was a suggestion of a slower progression of emphysema by computed
      tomography (CT) scan in a small randomized trial. Two nonrandomized studies
      comparing AAT-deficient patients already receiving replacement therapy with those
      not receiving it, and a retrospective study evaluating a decline in FEV(1) before
      and after replacement therapy, suggested a possible benefit for selected
      patients. Because of the lack of definitive proof of the clinical effectiveness
      of AAT replacement therapy and its cost, we recommend reserving AAT replacement
      therapy for deficient patients with impaired FEV(1) (35-65% of predicted value),
      who have quit smoking and are on optimal medical therapy but continue to show a
      rapid decline in FEV(1) after a period of observation of at least 18 months. A
      randomized placebo-controlled trial using CT scan as the primary outcome measure
      is required. Screening for AAT deficiency is recommended in patients with chronic
      irreversible airflow obstruction with atypical features such as early onset of
      disease or disability in their forties or fifties, or positive family history,
      and in immediate family members of patients with AAT deficiency.

PMID- 15725044
TI  - A meta-analytical approach to the efficacy of antihypertensive drugs in reducing
      blood pressure.
AB  - INTRODUCTION: Hypertension constitutes a veritable public health issue. Several
      classes of drugs are available for the treatment of hypertension. The objective
      of this meta-analytical approach was to assess the efficacy of antihypertensive
      drugs most commonly used in France in reducing clinical SBP and DBP. METHODS: The
      antihypertensive drugs selected were hydrochlorothiazide, indapamide sustained
      release (SR), furosemide and spironolactone for diuretics; amlodipine and
      lercanidipine for calcium channel antagonists; atenolol for beta-adrenoceptor
      antagonists (beta-blockers); enalapril and ramipril for ACE inhibitors; and
      candesartan cilexetil, irbesartan, losartan, and valsartan for angiotensin II
      receptor antagonists. The trials selected were published between 1973 and 2004,
      evaluated monotherapy with trial drugs as fixed-dosage or with dosage increase,
      and assessed blood pressure reduction between 2 and 3 months. The analysis method
      used was based on the calculation of the sum weighted for the trial size.
      RESULTS: A total of 72 trials (comprising 9094 patients) were selected and
      analyzed. No trial evaluating furosemide or spironolactone satisfied the
      inclusion criteria for this analysis. For SBP, the reduction was more marked with
      diuretics, calcium channel antagonists, and ACE inhibitors. Of all the drugs
      studied, indapamide SR gave the greatest SBP reduction (-22.2 mm Hg). Evaluated
      therapeutic classes had a similar magnitude of effect on DBP, i.e. reduction
      between -11.4 mm Hg with beta-adrenoceptor antagonists and -10.3 mm Hg with
      angiotensin II type 1 receptor antagonists. CONCLUSION: Indapamide SR 1.5 mg
      appeared to be the most effective drug for a significant reduction in SBP within
      2-3 months, which is an essential element in optimizing cardiovascular prevention
      among hypertensive patients. The clinical application of these results should
      take into consideration all the limitations discussed in this analysis.

PMID- 15725046
TI  - Asthma management issues in infancy and childhood.
AB  - The prevalence of asthma has been increasing worldwide over the past 2 decades,
      especially the prevalence of childhood asthma. Currently, the prevalence of
      childhood asthma is around 3-20% in different countries based on the report from
      the International Study of Asthma and Allergies in Children (ISAAC). Asthma in
      childhood is predominantly an extrinsic asthma. In general, countries in the
      coastal, temperate, and subtropical zones have the highest prevalence of mite-
      and cockroach-sensitive asthma. Countries in the sub-arctic or semi-arid areas
      have a lower prevalence of childhood asthma, mostly associated with sensitization
      to pet dander, moulds, and pollens. Many genes have been linked to asthma in
      different ethnic populations. A global consensus for the management of asthma in
      adults and children >5 years of age has been made possible in the Global
      Initiative for Asthma (GINA) guidelines, where a step-wise management program
      using inhaled medication with and without oral anti-inflammatory drugs is
      recommended. The management of asthma in children <5 years of age remains
      inconclusive. Recent studies suggest that inherited susceptibility associated
      with risk factors from the prenatal and postnatal environment is likely to
      promote allergic sensitization and development of asthma. Consequently, early
      prevention of prenatal sensitization in utero and environmental control of early
      life exposure to various allergens may decrease the incidence of childhood
      asthma. In the management of moderate persistent asthma in infants and young
      children <5 years of age, airway resistance tests (FEV(1) or PEF) are not of
      significance, but assessment of respiratory rate and skin pulse oximeter
      measurements of arterial oxygen saturation are helpful. Moreover, recent advances
      in pharmacogenetics and pharmacogenomics may provide better individualized care
      for early pharmacological prevention of childhood asthma via selective modulation
      of airway remodeling.

PMID- 15725047
TI  - Rhinitis medicamentosa: a review of causes and treatment.
AB  - Rhinitis medicamentosa (RM) is a drug-induced, nonallergic form of rhinitis that
      is associated with prolonged use of topical vasoconstrictors, i.e. local
      decongestants. Symptoms are exacerbated by the preservative benzalkonium chloride
      (BKC) in the nasal preparations. Nasal stuffiness is caused by rebound swelling
      of the mucosa when the decongestive effect of the drug has disappeared. To
      alleviate this symptom, patients gradually start using larger doses of the
      vasoconstrictor more frequently. In many cases, the patient is unaware of the
      condition, thus entering a vicious circle of self-treatment. Careful questioning
      is required during consultation to establish diagnosis. The pathophysiology of
      the condition is unclear; however, vasodilatation and intravascular edema have
      both been implicated. Management of RM requires withdrawal of topical
      decongestants to allow the damaged nasal mucosa to recover, followed by treatment
      of the underlying nasal disease. Topical corticosteroids such as budesonide and
      fluticasone propionate should be used to alleviate rebound swelling of the nasal
      mucosa. Where possible, avoiding exposure to BKC is recommended.

PMID- 15725048
TI  - Once-daily azithromycin for 3 days compared with clarithromycin for 10 days for
      acute exacerbation of chronic bronchitis: a multicenter, double-blind, randomized
      study.
AB  - STUDY OBJECTIVES: To compare the efficacy and safety of oral azithromycin 500 mg
      once daily for 3 days with those of oral clarithromycin 500 mg twice daily for 10
      days. DESIGN: Randomized, double-blind, double-dummy, multicenter study. SETTING:
      Seventy-six study centers in eight countries (Argentina, Brazil, Canada, Chile,
      Costa Rica, India, South Africa, and USA). PATIENTS: Three hundred and twenty-two
      adult outpatients with acute exacerbation of chronic bronchitis (AECB) as
      documented by increased cough or sputum production, worsening dyspnea, and
      purulent sputum production. INTERVENTIONS: Randomization 1 : 1 to azithromycin
      500 mg once daily for 3 days or clarithromycin 500 mg twice daily for 10 days.
      RESULTS: The primary efficacy endpoint was clinical response at day 21-24, or
      test of cure (TOC) visit in the modified intent-to-treat (MITT) analysis (n = 318
      patients). The TOC clinical cure rates in the MITT population were equivalent in
      the two treatment groups at 85% with azithromycin and 82% with clarithromycin
      (95% CI -5.9%, 12.0%). Clinical success rates on day 10-12 were also equivalent
      at 93% with azithromycin and 94% with clarithromycin (95% CI -7.9%, 4.4%).
      Clinical cure rates at TOC by pathogen were equivalent for the two treatment
      groups for Haemophilus influenzae (azithromycin, 85.7%; clarithromycin, 87.5%),
      Moraxella catarrhalis (91.7% and 80.0%, respectively) and Streptococcus
      pneumoniae (90.6% and 77.8%, respectively). Bacteriologic success rates were also
      equivalent between the azithromycin and clarithromycin treatment groups at TOC
      for S. pneumoniae (90.6% and 85.2%, respectively), H. influenzae (71.4% and
      81.3%, respectively) and M. catarrhalis (100% and 86.7%, respectively). The
      overall incidence of treatment-related adverse events was similar in the
      azithromycin and clarithromycin groups (20.9% and 26.8%, respectively), with the
      most common being abdominal pain (6.3% and 6.1%, respectively), diarrhea (4.4%
      and 5.5%, respectively), and nausea (4.4% and 3.7%, respectively). CONCLUSIONS:
      Three-day treatment with azithromycin 500 mg once daily is equivalent to a 10-day
      treatment with clarithromycin 500 mg twice daily in adult patients with AECB.

PMID- 15725049
TI  - Development and validation of a patient satisfaction and preference questionnaire
      for inhalation devices.
AB  - INTRODUCTION: The Patient Satisfaction and Preference Questionnaire (PASAPQ) is a
      multi-item measure of respiratory inhalation device satisfaction and preference
      designed to be easily understood and administered to patients with asthma and
      COPD. This study assessed its validity, reliability and responsiveness and
      explored the between-group difference in PASAPQ scores that is meaningful.
      METHODS: The field test version was developed using literature, focus groups and
      expert opinion. Item reduction followed. The assessment of the validity,
      reliability and responsiveness of the PASAPQ utilized data from two clinical
      studies comparing devices delivering the same medication, and was performed with
      pre-specified criteria. A minimally important difference (MID) was estimated
      using both anchor- and distribution-based approaches. RESULTS: Two factors of the
      PASAPQ, 'performance' and 'convenience', were consistent across studies. Missing
      and out-of-range data were minimal (<1%) and respondents used a full range of
      response options. All items correlated most highly with their hypothesized scale
      and all exceeded the minimum correlation criteria of 0.40. Cronbach's alfa was
      high (0.87-0.94), providing support for internal reliability for the PASAPQ.
      Correlations of the overall satisfaction item with the performance domain ranged
      from 0.78 to 0.91, the convenience domain ranged from 0.54 to 0.71, and the total
      score ranged from 0.78 to 0.90. These moderate-to-strong correlations provide
      substantial support for the validity of the PASAPQ domains and total score.
      Discriminate validity was assessed by calculating PASAPQ scores for patients'
      ratings of the device that they preferred compared with the other, non-preferred
      device. The preferred device was rated higher on all satisfaction measures,
      supporting the ability of the PASAPQ to discriminate between preferred and non
      preferred devices. Although a difference of 3 or 4 points may be sufficient to
      observe a small effect difference between groups, most of the MID estimates were
      in the 8-10 point range. DISCUSSION AND CONCLUSION: Our analyses across asthma,
      COPD and patients with mixed respiratory disease (with features of both COPD and
      asthma), study designs and data sets lead us to conclude that the PASAPQ is a
      practical, valid, reliable and responsive instrument for measuring respiratory
      device satisfaction. Furthermore, a difference in satisfaction scores between
      treatment groups of 10 points is, conservatively, a difference that is meaningful
      to patients.

PMID- 15725051
TI  - The Novolizer: a multidose dry powder inhaler.
AB  - The Novolizer is a multidose, refillable, breath-actuated dry powder inhaler that
      delivers up to 200 metered doses of drug from a single cartridge. It has a
      multiple-feedback control mechanism to ensure that the inhalation was performed
      correctly. In randomized studies, almost all patients with asthma or COPD using
      the Novolizer, including those using the device for the first time and children,
      were able to generate sufficient peak inspiratory flow rates (PIFRs) to overcome
      the trigger threshold of the device. Comparative studies have shown that patients
      generate significantly higher PIFR through the Novolizer than through the
      Turbuhaler. At PIFR of 54-99 L/min through the Novolizer, the median deposition
      of budesonide in the lungs of healthy volunteers was 19.9-32.1%. Two randomized,
      double-blind trials in patients with asthma showed that the clinical efficacy of
      drugs delivered through the Novolizer in terms of improvement in FEV(1) was at
      least as good as that of an identical treatment regimen delivered through the
      Aerolizer (for formoterol) or the Sultanol (for albuterol [salbutamol]).
      Similarly, therapeutic equivalence was also shown between budesonide delivered
      through the Novolizer and that through the Turbuhaler in patients with COPD or
      asthma in a randomized, nonblind study. Device-related adverse events were not
      reported in patients using the Novolizer in therapeutic trials and in a large (n
      > 3000) post-marketing surveillance study. Overall, the Novolizer was well
      accepted, with an improved compliance in 80% of patients that was attributable to
      the control mechanisms of the device.

PMID- 15725050
TI  - Respimat Soft Mist inhaler versus hydrofluoroalkane metered dose inhaler: patient
      preference and satisfaction.
AB  - INTRODUCTION: In addition to offering favorable pharmaceutical performance, an
      ideal inhaler should be well accepted by patients, as this may facilitate
      compliance. We report a study that specifically assessed inhaler preference in
      patients with obstructive lung disease after treatment with ipratropium
      bromide/fenoterol hydrobromide (Berodual delivered via either Respimat Soft Mist
      Inhaler (SMI) or hydrofluoroalkane metered dose inhaler (HFA-MDI). METHODS:
      Patients with COPD, asthma or mixed disease were randomized to receive
      ipratropium bromide/fenoterol hydrobromide 20/50 microg via Respimat SMI or
      40/100 microg via HFA-MDI for 7 weeks each, in a crossover design. Patients were
      trained in inhaler use and given < or =5 attempts to demonstrate satisfactory
      technique. At the end of each treatment period, patients completed a 15-item
      satisfaction questionnaire, and inhaler technique was re-tested. On study
      completion, patients were asked which inhaler they preferred and they rated their
      willingness to continue using each inhaler. Clinical efficacy outcomes were
      measured by diary card to check whether switching inhaler affected efficacy.
      RESULTS: In total, 245 patients were randomized and 224 used both inhalers within
      their respective treatment periods. Of 201 patients expressing a preference, 162
      (81%) preferred Respimat SMI and 39 (19%) preferred HFA-MDI (p < 0.001). Patients
      would rather continue using Respimat SMI than HFA-MDI (p < 0.001). Mean scores
      for 13 of the 15 satisfaction questions were significantly higher for Respimat
      SMI than HFA-MDI (p < 0.05); in addition, the total score was also significantly
      higher for Respimat SMI (p < 0.001). Most patients (217/224; 97%) were judged to
      have good technique with Respimat SMI after 7 weeks' use. Differences in efficacy
      measures between the devices were not significant. CONCLUSION: These data
      indicated that a large majority of patients preferred Respimat SMI to HFA-MDI.

PMID- 15725052
TI  - The Novolizer: a multidose dry powder inhaler: a viewpoint by Peter Haidl.

PMID- 15725053
TI  - The Novolizer: a multidose dry powder inhaler: a viewpoint by Stephen P. Newman.

PMID- 15725054
TI  - An unforeseen voyage to the world of phytochromes.

PMID- 15725055
TI  - Alternative NAD(P)H dehydrogenases of plant mitochondria.
AB  - Plant mitochondria have a highly branched electron transport chain that provides
      great flexibility for oxidation of cytosolic and matrix NAD(P)H. In addition to
      the universal electron transport chain found in many organisms, plants have
      alternative NAD(P)H dehydrogenases in the first part of the chain and a second
      oxidase, the alternative oxidase, in the latter part. The alternative activities
      are nonproton pumping and allow for NAD(P)H oxidation with varying levels of
      energy conservation. This provides a mechanism for plants to, for example, remove
      excess reducing power and balance the redox poise of the cell. This review
      presents our current understanding of the alternative NAD(P)H dehydrogenases
      present in plant mitochondria.

PMID- 15725056
TI  - DNA methylation and epigenetics.
AB  - In many eukaryotes, including plants, DNA methylation provides a heritable mark
      that guides formation of transcriptionally silent heterochromatin. In plants,
      aberrant RNA signals direct DNA methylation to target sequences, sometimes
      appropriately and sometimes inappropriately. This chapter discusses the
      generation of RNA signals for epigenetic changes, the factors that mediate those
      changes, and some of the consequences of those changes for plant gene expression
      and genome integrity.

PMID- 15725057
TI  - Phosphoenolpyruvate carboxylase: a new era of structural biology.
AB  - There have been remarkable advances in our knowledge of this important enzyme in
      the last decade. This review focuses on three recent topics: the three
      dimensional structure of the protein, molecular mechanisms of catalytic and
      regulatory functions, and the molecular cloning and characterization of PEPC
      kinases, which are Ser/Thr kinases involved specifically in regulatory
      phosphorylation of vascular plant PEPC. Analysis by X-ray crystallography and
      site-directed mutagenesis for E. coli and maize PEPC identified the catalytic
      site and allosteric effector binding sites, and revealed the functional
      importance of mobile loops. We present the reaction mechanism of PEPC in which we
      assign the roles of individual amino acid residues. We discuss the unique
      molecular property of PEPC kinase and its possible regulation at the post
      translational level.

PMID- 15725058
TI  - Metabolic channeling in plants.
AB  - The organization of cooperating enzymes into macromolecular complexes is a
      central feature of cellular metabolism. A major advantage of such spatial
      organization is the transfer of biosynthetic intermediates between catalytic
      sites without diffusion into the bulk phase of the cell. This so-called
      "metabolic channeling" offers unique opportunities for enhancing and regulating
      cellular biochemistry. Studies in a number of plant primary and secondary
      metabolic systems continue to contribute to our understanding of the nature and
      importance of this phenomenon. This article reviews advances in four systems: the
      cysteine synthase complex, the Calvin cycle, cyanogenic glucoside biosynthesis,
      and the phenylpropanoid pathway. Each of these systems is providing new evidence
      for the importance of enzyme organization in cellular biochemistry as well as
      exclusive insights into the molecular basis of enzyme complex assembly. This
      review also explores current prospects for understanding metabolon structure,
      assembly, and biological function.

PMID- 15725062
TI  - Fondaparinux.
AB  - Fondaparinux is the first drug from the pentassaccharide factor X inhibitor class
      of anticoagulants to be approved for clinical use. It has been shown to be
      effective in the prevention of deep vein thrombosis in patients undergoing major
      orthopaedic surgery of the lower limbs. The drug is also being evaluated for use
      in the acute coronary syndromes and established thromoboembolic events. The
      pharmacology of fondaparinux is discussed in this review, as well as the major
      clinical trials involving this drug. Arguments for (and against) the use of this
      drug are also summarised.

PMID- 15725063
TI  - Intracoronary brachytherapy--clinical state and pathophysiological
      considerations.
AB  - In-stent restenosis remains the limitation of coronary stent implantation despite
      numerous efforts of its prevention by catheter-based techniques or by drug
      therapy. Today, only intravascular irradiation has proven to effectively reduce
      neointima formation, restenosis rate and major adverse cardiovascular events by
      approximately 50%. Its efficiency is demonstrated for high-risk subsets like long
      lesions, lesions in saphenous venous bypass grafts or diabetic patients,
      indicating the extraordinary potential of vascular irradiation. Yet vascular
      irradiation has some limitations. Edge effect describes the phenomenon of
      excessive neointimal proliferation at the edges of an irradiated segment and is
      likely due to axial dose fall-off and/ or barotrauma by the angioplasty
      procedure. Geographic miss, the combination of dose fall-off and vessel injury
      may be deleterious, especially if a new stent is implanted. The use of
      appropriate radiation source lengths to avoid geographic miss substantially
      reduces the incidence of edge effect. Late thrombosis, occurring even years after
      irradiation, had significantly diminished the benefit of vascular irradiation in
      initial clinical trials, but extension of ntiplatelet therapy up to 12 months
      after irradiation has reduced its rates to placebo levels. Vascular brachytherapy
      is of considerable clinical benefit in the prevention of restenosis and the only
      proven option for the treatment of in-stent restenotic lesions. This review will
      focus on the mechanisms of action of vascular irradiation, on the
      pathophysiological reasons for its complications and therapeutic options. Both
      angiographic and clinical results of randomised and observational studies will be
      updated in detail.

PMID- 15725064
TI  - Levosimendan: a new inodilatory drug for the treatment of decompensated heart
      failure.
AB  - Levosimendan is a new calcium sensitizer developed for the treatment of
      congestive heart failure. Experimental studies indicate that levosimendan
      increases myocardial contractility and dilates both the peripheral and coronary
      vessels. Its positive inotropic effect is based on calcium-dependent binding of
      the drug to cardiac troponin C. It also acts as an opener of ATP-dependent
      potassium channels in vascular smooth muscle, thus inducing vasodilation.
      Although levosimendan acts preferentially as a calcium sensitizer it has also
      demonstrated selective phosphodiesterase III inhibitory effects in vitro.
      However, this selective inhibition does not seem to contribute to the positive
      action at pharmacologically relevant concentrations. Levosimendan has an active
      metabolite, OR-1896. Similarly to levosimendan, the metabolite exerts its
      positive inotropic and vasodilatory effects on myocardium and vasculature. The
      elimination half-life of levosimendan is about 1 hour. Thus, with intravenous
      administration, the parent drug rapidly disappears from the circulation after the
      infusion is stopped. The active metabolite, however, has a half-life of
      approximately 80 hours, and can be detected in circulation up to 2 weeks after
      stopping a 24-hour infusion of levosimendan. The intravenous formulation of
      levosimendan has been studied in several randomized comparative studies in
      patients with decompensated heart failure. Both patients with ischemic and non
      ischemic etiology have participated in the studies. Levosimendan produces
      significant, dose-dependent increases in cardiac output, stroke volume and heart
      rate, and decreases in PCWP, mean blood pressure, mean pulmonary artery pressure,
      mean right atrial pressure and total peripheral resistance. With a loading dose,
      the effects on PCWP and cardiac ouput are seen within few minutes. There is no
      sign of development of tolerance even with a prolonged infusion up to 48 hours.
      Cardiac performance is improved with no significant increases in oxygen
      consumption or potentially malignant rhythm disorders. Due to the formation of an
      active metabolite, the hemodynamic effects are maintained up to several days
      after stopping levosimendan infusion. Compared to dobutamine, levosimendan
      produces similar increase in cardiac output but profoundly greater decrease in
      pulmonary capillary wedge pressure. On the contrary to dobutamine, the
      hemodynamic effects are not attenuated with concomitant beta-blocker use.
      Levosimendan has been shown to have favourable effects on symptoms of heart
      failure superior to placebo and at least comparable to dobutamine. Mortality and
      morbidity in levosimendan treated patients has been shown to be significantly
      lower when compared to dobutamine or placebo treated patients. The most common
      adverse events associated with levosimendan treatment are headache and
      hypotension, as a likely consequence of the vasodilating properties of the
      compound. In conclusion, levosimendan offers a new effective option for the
      treatment of acutely decompensated heart failure. Unlike traditional inotropes,
      levosimendan seems also to be safe in terms of morbidity and mortality.

PMID- 15725066
TI  - Fibrosis as a therapeutic target post-myocardial infarction.
AB  - The extracellular matrix (ECM) is a dynamic microenvironment and a major
      contributor to the adverse ventricular remodelling that follows myocardial
      infarction (MI), via activation of both direct pro-fibrotic pathways and matrix
      metalloproteinases (MMPs) that enhance collagenase activity. Reactive fibrosis,
      i.e. deposition of ECM materials remote from the region of the MI is clearly
      detrimental to ventricular function and contributory to adverse outcomes post-MI.
      Therefore, reversal of this process represents an important therapeutic target in
      post-MI management and treatment of established heart failure. A number of
      existing agents exert their beneficial effects in part via reductions in ECM
      deposition. Furthermore, specific anti-fibrotic drugs have been developed and are
      currently being explored for these and other cardiac conditions where
      pathological ECM deposition is felt to be contributory to disease progression.

PMID- 15725065
TI  - Clinical applications of cardiovascular magnetic resonance.
AB  - The clinical role of magnetic resonance in diseases of the heart and great
      vessels is rapidly evolving. Cardiovascular magnetic resonance (CMR) has become
      an established non-invasive imaging modality for the assessment of various
      cardiac disorders, such as congenital heart disease, cardiac masses,
      cardiomyopathies, aortic and pericardial diseases. Moreover, due to its accuracy
      and reproducibility, CMR is currently considered the gold standard for
      quantification of ventricular volumes, function, and mass. Thus, this technique
      is ideally suited to assess the efficacy of therapeutic interventions on
      ventricular hypertrophy and remodelling, which may allow a reduction in sample
      size to show clinically relevant effects. Comprehensive functional assessment is
      possible by CMR due to its capability to measure flow velocity and flow volume,
      which is a basic requirement to quantify lesion severity in valvular heart
      disease. Within the past years, major technical advances have considerably
      improved acquisition speed and image quality making CMR a useful tool for the
      evaluation of patients with ischaemic heart disease. Although the clinical
      robustness of coronary magnetic resonance angiography still needs improvement,
      CMR currently provides valuable information to detect reversible ischemia,
      myocardial infarction, and residual viability. In this review we will present in
      detail the well-established indications of CMR accompanied by an outlook on new
      applications that are likely to enter the clinical arena in the near future.

PMID- 15725067
TI  - Effectors of fatty acid oxidation reduction: promising new anti-ischaemic agents.
AB  - The heart is a pump, but also a furnace able to produce at each moment a large
      amount of energy and to adapt fast enough to face the changes in both fuel supply
      and energy demand. The pharmacological treatment of angina has been largely
      focused on the "pump" through hemodynamic agents aimed at decreasing cardiac
      effort to decrease energy demand. A new concept arose focusing the "furnace"
      through metabolic agents aimed at decreasing the oxygen cost of ATP production.
      This goal can be achieved by shifting energy production from fatty acid beta
      oxidation to glucose oxidation. CPT1 inhibitors were developed to prevent the
      fatty acid entry into mitochondria but induced cardiac hypertrophy. Regulation of
      carnitine biology either by carnitine supply or by gamma-butyrobetaine
      hydroxylase inhibitors have led to controversial data both in pharmacological and
      clinical concerns. Trimetazidine and ranolazine increase the glucose/fatty acid
      oxidation balance and exhibit beneficial effects in animal studies as well as in
      clinical trials, both in monotherapy and in association with a traditional
      hemodynamic drug. The association of metabolic and hemodynamic agents brings
      additive benefits in angina, whereas associations of hemodynamics do not. The
      mechanism of these drugs has not been fully understood in terms of specific
      target. In animal studies, dietary docosahexaenoic acid allowed similar
      protection, through a mechanism related to membrane conformation without specific
      enzymic target. From the mechanistic research published in this field, enough has
      now been understood to foresee some future possible targets, mainly related to
      the cardiomyocyte fatty acid metabolism.

PMID- 15725068
TI  - The diagnostic and prognostic value of brain natriuretic peptide and
      aminoterminal (nt)-pro brain natriuretic peptide.
AB  - The discovery of B-type natriuretic peptide (BNP) and n-terminal pro BNP (nt
      proBNP) as markers for the diagnosis, severity and prognosis of patients with
      congestive heart failure has been called a true breakthrough for patients and
      physicians faced with this disorder. Moreover, the literature on their prognostic
      value in other clinical conditions like acute coronary syndromes, right-sided
      heart failure and even in the general population is rapidly growing. This review
      aims to sort out the current evidence on the clinical utility of the natriuretic
      peptides with a focus on their diagnostic and prognostic values. With respect to
      their diagnostic properties, the test is best used to rule out heart failure in
      patients with acute dyspnoe, because low levels of these neurohormones in this
      clinical context make the presence of heart failure very unlikely. In patients
      with elevated values of BNP or nt-proBNP, further cardiological assessment is
      necessary, as their plasma levels are affected not only by left ventricular
      function.

PMID- 15725069
TI  - Ximelagatran--a promising new drug in thromboembolic disorders.
AB  - Ximelagatran is an oral direct thrombin inhibitor (DTI), the active form of which
      is melagatran. Approximately 20% of an oral ximelagatran dose becomes
      bioavailable as melagatran, which binds noncovalently and reversibly to both
      fibrin-bound and freely circulating thrombin. Oral ximelagatran dosing not only
      inhibits thrombin activity rapidly, competitively, and potently, but also delays
      and suppresses thrombin generation. In humans, oral ximelagatran exhibits
      anticoagulant, antiplatelet, and profibrinolytic effects, with only minor
      prolongation of the capillary bleeding time. Oral ximelagatran exhibits a stable
      and predictable pharmacokinetic profile during repeated dosing, with low intra-
      and inter-individual variation, and a low potential for interaction with other
      medications. It is excreted primarily as melagatran via the kidney, without
      unexpected bioaccumulation. Dosing requirements do not vary with age, gender,
      ethnicity, obesity, or food or alcohol intake. Clinical trials (total n>30,000)
      have evaluated oral ximelagatran in four indications: the prevention of venous
      thromboembolism (VTE, comprising deep venous thrombosis with or without and
      pulmonary embolism) after elective hip- or knee-replacement surgery (with
      approval granted by France, as the Reference Member State for the European
      Union); treatment and long-term secondary prevention of VTE; the prevention of
      stroke and other systemic embolic events associated with nonvalvular atrial
      fibrillation; and the prevention of cardiovascular events after an acute
      myocardial infarction. The results of these trials suggest that the benefit-risk
      profile of oral ximelagatran therapy, administered at a fixed-dose without
      coagulation monitoring, compares favorably with that of currently approved
      standard therapy.

PMID- 15725070
TI  - Leptin, immune responses and autoimmune disease. Perspectives on the use of
      leptin antagonists.
AB  - The pivotal role of leptin in regulating body weight and energy homeostasis is
      very well established. More recently, leptin also emerged as an important
      regulator of T-cell-dependent immunity. Reduced leptin levels, as observed during
      periods of starvation, correlate with an impaired cellular immune response,
      whereby especially the T(H)1 pro-inflammatory immune response appears to be
      affected. Physiologically, this could reflect the high energy demand of such
      processes, which are suppressed in animals or people with nutrient shortage.
      Several autoimmune diseases are T(H)1 T-cell dependent. In line with a pro
      inflammatory role for leptin, animal models of leptin deficiency are markedly
      resistant to a variety of T-cell dependent autoimmune diseases. Here, we review
      the role of leptin in immune responses, with emphasis on autoimmune diseases. The
      design and potential use of leptin antagonists is also discussed.

PMID- 15725071
TI  - Protein kinase C isozyme selective peptides--a current view of what they tell us
      about location and function of isozymes in the heart.
AB  - The identification of protein kinase C isozymes in distinct localities within the
      cell has led to the suggestion that each isozyme mediates a unique function. This
      has necessitated the development of methodologies that are capable of assigning
      specific function to an isozyme. For many years the location of individual
      isozymes in a particulate fraction was used to correlate specific isozymes with
      cellular function. More recently over-expression of selective isozymes and
      genetic knockouts have provided tissue-specific and developmentally regulated
      information on function. It is now known that specific proteins act as isozyme
      selective receptors for activated C kinase (RACKs) which determine subcellular
      localization of specific isozymes. As a result, peptides have been designed from
      the interaction site between the isozyme and its RACK that prevent the binding of
      isozymes to their respective RACKs. This has allowed the modulation of function
      of individual isozymes. This review will examine the development of the peptides
      as isozyme selective inhibitors or activators of PKC and its impact on
      understanding the role of isozymes in cellular function in the healthy and
      diseased heart. The possible development of isozyme-specific drugs for
      therapeutic use will be discussed.

PMID- 15725072
TI  - Identification and functional characterization of a novel Candida albicans gene
      CaMNN5 that suppresses the iron-dependent growth defect of Saccharomyces
      cerevisiae aft1Delta mutant.
AB  - In Saccharomyces cerevisiae, the transcription factor Aft1p plays a central role
      in regulating many genes involved in iron acquisition and utilization. An
      aft1Delta mutant exhibits severely retarded growth under iron starvation. To
      identify the functional counterpart of AFT1 in Candida albicans, we transformed a
      C. albicans genomic DNA library into aft1Delta to isolate genes that could allow
      the mutant to grow under iron-limiting conditions. In the present paper, we
      describe the unexpected discovery in this screen of CaMNN5. CaMnn5p is an alpha
      1,2-mannosyltransferease, but its growth-promoting function in iron-limiting
      conditions does not require this enzymatic activity. Its function is also
      independent of the high-affinity iron transport systems that are mediated by
      Ftr1p and Fth1p. We obtained evidence suggesting that CaMnn5p may function along
      the endocytic pathway, because it cannot promote the growth of end4Delta and
      vps4Delta mutants, where the endocytic pathway is blocked at an early and late
      step respectively. Neither can it promote the growth of a fth1Delta smf3Delta
      mutant, where the vacuole-cytosol iron transport is blocked. Expression of CaMNN5
      in S. cerevisiae specifically enhances an endocytosis-dependent mechanism of iron
      uptake without increasing the uptake of Lucifer Yellow, a marker for fluid-phase
      endocytosis. CaMnn5p contains three putative Lys-Glu-Xaa-Xaa-Glu iron-binding
      sites and co-immunoprecipitates with 55Fe. We propose that CaMnn5p promotes iron
      uptake and usage along the endocytosis pathway under iron-limiting conditions, a
      novel function that might have evolved in C. albicans.

PMID- 15725073
TI  - Gene duplication, gene loss and evolution of expression domains in the vertebrate
      nuclear receptor NR5A (Ftz-F1) family.
AB  - Fushi tarazu factor 1 (Ftz-F1, NR5A) is a zinc-finger transcription factor that
      belongs to the nuclear receptor superfamily and regulates genes that are involved
      in sterol and steroid metabolism in gonads, adrenals, liver and other tissues. To
      understand the evolutionary origins and developmental genetic relationships of
      the Ftz-F1 genes, we have cloned four homologous Ftz-f1 genes in zebrafish,
      called ff1a, ff1b, ff1c and ff1d. These four genes have different temporal and
      spatial expression patterns during development, indicating that they have
      distinct mechanisms of genetic regulation. Among them, the ff1a expression
      pattern is similar to mammalian Nr5a2, while the ff1b pattern is similar to that
      of mammalian Nr5a1. Genetic mapping experiments show that these four ff1 genes
      are located on chromosome segments conserved between the zebrafish and human
      genomes, indicating a common ancestral origin. Phylogenetic and conserved synteny
      analysis show that ff1a is the orthologue of NR5A2, and that ff1b and ff1d genes
      are co-orthologues of NR5A1 that arose by a gene-duplication event, probably a
      whole-genome duplication, in the ray-fin lineage, and each gene is located next
      to an NR6A1 co-orthologue as in humans, showing that the tandem duplication
      occurred before the divergence of human and zebrafish lineages. ff1c does not
      have a mammalian counterpart. Thus we have characterized the phylogenetic
      relationships, expression patterns and chromosomal locations of these Ftz-F1
      genes, and have demonstrated their identities as NR5A genes in relation to the
      orthologous genes in other species.

PMID- 15725074
TI  - The tetraspanin D6.1A and its molecular partners on rat carcinoma cells.
AB  - Tetraspanins function as molecular organizers of multi-protein complexes by
      assembling primary complexes of a relatively low mass into extensive networks
      involved in cellular signalling. In this paper, we summarize our studies
      performed on the tetraspanin D6.1A/CO-029/TM4SF3 expressed by rat carcinoma
      cells. Primary complexes of D6.1A are almost indistinguishable from complexes
      isolated with anti-CD9 antibody. Indeed, both tetraspanins directly associate
      with each other and with a third tetraspanin, CD81. Moreover, FPRP (prostaglandin
      F2alpha receptor-regulatory protein)/EWI-F/CD9P-1), an Ig superfamily member that
      has been described to interact with CD9 and CD81, is also a prominent element in
      D6.1A complexes. Primary complexes isolated with D6.1A-specific antibody are
      clearly different from complexes containing the tetraspanin CD151. CD151 is found
      to interact only with D6.1A if milder conditions, i.e. lysis with LubrolWX
      instead of Brij96, are applied to disrupt cellular membranes. CD151 probably
      mediates the interaction of D6.1A primary complexes with alpha3beta1 integrin. In
      addition, two other molecules were identified to be part of D6.1A complexes at
      this higher level of association: type II phosphatidylinositol 4-kinase and
      EpCAM, an epithelial marker protein overexpressed by many carcinomas. The
      characterization of the D6.1A core complex and additional more indirect
      interactions will help to elucidate the role in tumour progression and metastasis
      attributed to D6.1A.

PMID- 15725075
TI  - Down-regulation of Rap1 activity is involved in ephrinB1-induced cell
      contraction.
AB  - Ephrins are cell surface ligands that activate Eph receptor tyrosine kinases.
      This ligand-receptor interaction plays a central role in the sorting of cells. We
      have previously shown that the ephrinB-EphB signalling pathway is also involved
      in the migration of intestinal precursor cells along the crypts. Using the colon
      cell line DLD1 expressing the EphB2 receptor, we showed that stimulation of these
      cells with soluble ephrinB1 results in a rapid retraction of cell extensions and
      a detachment of cells. On ephrinB1 stimulation, the small GTPases Rho and Ras are
      activated and Rap1 is inactivated. Importantly, when a constitutively active Rap1
      mutant was introduced into these cells, ephrinB1-induced retraction was
      inhibited. From these results, we conclude that down-regulation of Rap1 is a
      prerequisite for ephrin-induced cell retraction in colon cells.

PMID- 15725076
TI  - Bilateral optic disc oedema as the initial manifestation of leukaemic relapse.

PMID- 15725078
TI  - Modern management of myelofibrosis.
AB  - The conventional treatment of myelofibrosis involves a wait-and-see approach for
      asymptomatic patients, oral chemotherapy for the hyperproliferative forms of the
      disease, androgens or erythropoietin for the anaemia, and splenectomy in selected
      patients. Low-dose thalidomide plus prednisone is a well-tolerated therapy for
      the anaemia and the thrombocytopenia of myelofibrosis, whereas imatinib has shown
      little efficacy. Allogeneic stem cell transplantation (allo-SCT) is the only
      curative therapy for myelofibrosis. Its standard modality has an associated
      mortality of about 30% and can be applied to younger patients with high-risk
      disease or resistant to conventional treatment. Reduced-intensity conditioning
      allo-SCT involves a low mortality and is a promising therapy for patients aged 45
      70 years old with the above characteristics. Autologous SCT is a palliative
      therapy for patients resistant to conventional treatment who lack a suitable
      donor. The next candidates for the treatment of myelofibrosis are the thalidomide
      derivatives, the proteasome inhibitors, and vascular endothelial growth factor
      neutralizing antibodies.

PMID- 15725077
TI  - Pohl-Pinkus constrictions of hair following chemotherapy for Hodgkin's disease.

PMID- 15725079
TI  - Low molecular weight heparin in pregnancy: current issues.
AB  - Low molecular weight heparin (LMWH) is now the most commonly used anticoagulant
      for prophylaxis and treatment of venous thromboembolism in pregnancy and the
      puerperium in the UK. The reliable pharmacokinetics of LMWHs and their long half
      life, resulting in the need for less frequent injections than unfractionated
      heparin (UFH), makes them attractive for practical use in the 9 months of
      pregnancy. Widespread use over the last 10 years has shown that LMWHs are safer
      than UFH in pregnancy. There is, however, poor consensus and wide disparity of
      views among experts with regard to the appropriate dose for the varying
      indications, the duration of treatment, and whether and how LMWH should be
      monitored because of the lack of an evidence base. These areas of uncertainty
      reflect the fact that clinical practice has grown largely through the publication
      of small trials, observational studies, personal experience and anecdote. Good
      clinical trials are urgently required.

PMID- 15725080
TI  - Targeting malignant B-cell lymphoma with a humanized anti-CD22 scFv-angiogenin
      immunoenzyme.
AB  - We report on the generation and functional characterization of a humanized
      immunoenzyme comprising a stable humanized single chain Fv (scFv) with grafted
      specificity of the anti-CD22 murine monoclonal antibody RFB4 and the human
      ribonuclease angiogenin (ANG). The fusion protein produced from transiently
      transfected mammalian Chinese hamster ovary cells could easily be purified to
      homogeneity, retained full ribonucleolytic activity, and efficiently killed
      CD22(+) tumour cells with an IC(50) of 56 nmol/l. In contrast, incubation of
      tumour cells with either ANG or scFv alone did not result in any cytotoxicity.
      Potent receptor-mediated killing of target cells, expected lack of extracellular
      toxicity, predictable low immunogenic potential, and ease of production, suggest
      that this novel immunoenzyme has potential for the immunotherapy of CD22(+)
      malignancies.

PMID- 15725081
TI  - Association of NAT and GST polymorphisms with non-Hodgkin's lymphoma: a
      population-based case-control study.
AB  - Several chemicals have been associated with risk of non-Hodgkin's lymphoma (NHL),
      many of which are substrates for N-acetyltransferase (NAT) and glutathione S
      transferase (GST) enzymes. We investigated the association between polymorphisms
      in genes coding for these enzymes and NHL risk in a population-based study (389
      cases and 535 controls). NAT1 slow genotype was associated with a slightly
      increased risk in women [odds ratios (OR) = 1.4; 95% confidence interval (CI) =
      0.9-2.3], but not in men. NAT2 slow genotype was not associated with risk in
      either sex. The two slow genotypes of NAT1 and NAT2 combined were associated with
      a minor increase of risk in women (OR = 1.4; 0.8-2.4). There was no association
      with the GSTM1 or GSTT1 null genotype in either sex, irrespective of histological
      subtypes. Individuals with GSTP1 Val homozygotes had non-significant excessive
      risk of marginal zone lymphoma (OR = 1.8; 0.6-5.1) and 'other' B-cell NHLs (OR =
      1.6; 0.7-3.6), but lower risk of diffuse large B-cell lymphoma (OR = 0.2; 0.1
      0.96). Risk did not elevate with an increasing number of high-risk GST alleles in
      either sex. In summary, although NAT1, NAT2, GSTM1, GSTT1, or GSTP1 polymorphisms
      do not appear to be associated with NHL risk overall, there might be gender
      specific and subtype-specific associations that require confirmation.

PMID- 15725082
TI  - Low-grade primary central nervous system lymphoma in immunocompetent patients.
AB  - Primary central nervous system lymphomas (PCNSL) are usually diffuse large B-cell
      non-Hodgkin's lymphomas (NHL). Here we characterize the clinical presentation,
      course and outcome of patients with low-grade PCNSL. Records of 332 patients
      screened for inclusion in three multicentre prospective trials were reviewed. Ten
      patients (3%) with a median age of 59 years and a median Karnofsky performance
      status of 70% were identified. Seven patients had B-cell and three had T-cell
      lymphoma. The median growth fraction was 4%. The radiological morphology was
      unusual for PCNSL in eight patients. Three patients underwent complete tumour
      resection, combined with chemotherapy in one patient and with chemotherapy plus
      local radiotherapy in another. Four patients received chemotherapy and three
      received chemotherapy plus whole-brain irradiation, resulting in four complete
      remissions, two no-change situations and one progressive disease. Patients had an
      overall survival (OAS) of 2-58+ months with a 2-year OAS of 67%. Low-grade PCNSL
      may differ from classical high-grade PCNSL in its clinical features and
      radiological morphology. The clinical course may be variable and frequently more
      indolent than in classical PCNSL.

PMID- 15725083
TI  - Activity of sirolimus in patients with myelodysplastic syndrome--results of a
      pilot study.
AB  - The pathophysiology of the myelodysplastic syndromes (MDS) involves disturbed
      regulation of angiogenesis, apoptosis, proliferation and differentiation as well
      as immune surveillance. Increasing data suggest that sirolimus might affect these
      pathways positively, thus being of possible therapeutic benefit in patients with
      this disease. Nineteen patients (n = 19) with a median age of 72 years (range 54
      80 years) diagnosed with MDS received sirolimus orally with a target blood
      concentration of 3-12 ng/ml. Sirolimus was administered for a median of 3.7
      months (range 0.3-11 months). Three patients [1 x refractory anaemia with excess
      blasts (RAEB)-2, 1 x RAEB-1, 1 x refractory cytopenia with multilineage
      dysplasia] showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x
      erythroid, 2 x platelet) haematological response according to International
      Working Group criteria. Major side-effects were hyperlipidaemia (n = 4),
      stomatitis (n = 3), thrombocytopenia (n = 2) and urinary tract infection (n = 1).
      These data suggest that sirolimus has activity in a subset of patients with more
      advanced MDS.

PMID- 15725084
TI  - Toxicity in standard melphalan-prednisone therapy among myeloma patients with
      renal failure--a retrospective analysis and recommendations for dose adjustment.
AB  - Haematological and infectious toxicity was correlated to renal function in 272
      newly diagnosed myeloma patients given standard dose melphalan-prednisone (MP) as
      initial treatment without dose adjustment for renal impairment. The glomerular
      filtration rate (GFR) was estimated by calculated creatinine clearance.
      Haematological toxicity was found to be significantly related to renal
      dysfunction. Haematological toxicity World Health Organization (WHO) grades 3-4
      after the first MP course was seen in 18%, 28% and 36% of patients with a
      creatinine clearance of >50, 30-50 and <30 ml/min respectively. WHO grades 3-4
      infections occurred in 6% and were not significantly related to renal function.
      We conclude that MP therapy can be used for initial therapy in myeloma patients
      with renal impairment but suggest that reduction of the melphalan dose should be
      considered in patients with a GFR of <30 ml/min. As only 2% of our patients had a
      clearance of < or =10 ml/min no conclusions can be drawn for this subgroup.

PMID- 15725085
TI  - Changes in gene expression profiles of multiple myeloma cells induced by arsenic
      trioxide (ATO): possible mechanisms to explain ATO resistance in vivo.
AB  - Multiple myeloma (MM) is an incurable plasma cell malignancy marked by eventual
      resistance to therapy. Although arsenic trioxide (ATO) can induce apoptosis in MM
      cell lines, the in vivo activity of ATO in MM has been disappointing. The
      existence of ATO resistance mechanisms in MM can be inferred. We sought to
      generate hypotheses for ATO resistance by studying the gene expression profiles
      of MM cells that survived in culture with 0.5 micromol/l ATO. Among the 31 genes
      whose quantitative levels of expression (QLE) significantly increased in ATO were
      haem oxygenase 1 (HO-1) and metallothionein-2A (MT-2A). Among the 56 genes whose
      QLE were significantly decreased were genes that modulate cell cycling [BTBD2 and
      IGFBP7 (mac25)] and sensitivity to reactive oxygen species (ROS) (BACH2). HO-1
      exerts an anti-apoptotic effect in ischaemic cells, and MT-2A chelates ATO
      intracellularly. Inhibition of HO-1 with tin protoporphyrin enhances ROS in MM
      cells in ATO, and addition of N-acetylcysteine increases MT-2A. Protective
      antioxidant responses occur in MM cells exposed to ATO, and may occur in stromal
      cells as well, and act to quench ROS and provide diffusible anti-apoptotic
      factors. They may also involve cysteine-rich proteins that chelate ATO and
      modulate redox-sensitive residues on proteins, such as nuclear factor kappa B and
      p53. A better understanding of ATO resistance will enable ATO to be combined with
      other agents for MM.

PMID- 15725086
TI  - Pregnancy improves neutropenia in T-cell large granular lymphocyte leukaemia.
AB  - The effect of pregnancy on T-cell large granular lymphocyte (LGL) leukaemia has
      not been previously described. We retrospectively reviewed the clinical features
      of three patients with T-cell LGL leukaemia; each of them had one or more
      pregnancies during disease evolution. Pregnancy was associated with sustained
      improvement in neutrophil count and concurrent reduction in lymphocytosis.
      Neutropenia returned in the non-pregnant state in all cases. A similar effect,
      induced by exogenous progesterone in one patient, suggests a role for
      progesterone in overcoming mechanisms of neutropenia in this disease. Pregnancy
      thus appears to have a beneficial effect on neutrophil count in T-cell LGL
      leukaemia.

PMID- 15725087
TI  - Children with myelodysplastic syndrome (MDS) and increasing mixed chimaerism
      after allogeneic stem cell transplantation have a poor outcome which can be
      improved by pre-emptive immunotherapy.
AB  - We recently reported that virtually all children with acute leukaemia and
      myelodysplastic syndrome (MDS) who develop the phenotype of increasing mixed
      chimaerism (MC) after allogeneic stem cell transplantation (allo-SCT) will
      relapse. We therefore performed a prospective, multi-centre study focused on
      children with MDS (n = 65; advanced MDS = 44, refractory cytopenia = 21) after
      allo-SCT in order to determine to what extent relapse can be prevented by pre
      emptive immunotherapy on the basis of increasing MC. Analyses of chimaerism in 44
      patients with advanced MDS revealed 31 cases with complete chimaerism (CC)/low
      level MC/transient MC, 11 cases with increasing MC and two cases with decreasing
      MC. The same analyses in 21 MDS patients with refractory cytopenia revealed 17
      cases with CC/low-level MC, one case with increasing MC and three cases with
      decreasing MC. Pre-emptive immunotherapy performed on each patient that showed
      increasing MC improved event-free survival from 0%, as seen in prior studies, to
      50%. We therefore conclude that pre-emptive immunotherapy is an effective
      treatment option to prevent impending relapse in children with MDS after allo
      SCT.

PMID- 15725088
TI  - Allogeneic peripheral blood stem cell graft composition affects early T-cell
      chimaerism and later clinical outcomes after non-myeloablative conditioning.
AB  - We have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20,
      natural killer (NK; CD3(-)/CD56(+)), NKT (CD3(+)/CD56(+)), DC1, and DC2 cells] of
      granulocyte colony-stimulating factor mobilized peripheral blood stem cells
      (PBSC) on early T-cell chimaerism and later clinical outcomes in 125 patients
      with haematological malignancies who received human leucocyte antigen (HLA)
      matched related grafts after non-myeloablative conditioning. Conditioning
      consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI
      preceded by either 90 mg/m(2) fludarabine (n = 62) or planned autologous
      haematopoietic cell transplantation (HCT) (n = 35). Post-transplant
      immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate
      analysis showed that higher numbers of grafted NK cells predicted higher early T
      cell chimaerism (P = 0.03), while higher numbers of B cells were associated with
      better clinical outcomes and a higher risk for chronic graft-versus-host disease
      (P = 0.05). Higher numbers of CD14(+) cells were associated with worse overall
      survival (P = 0.03), while higher numbers of CD34(+) cells showed better survival
      (P = 0.03). The addition of fludarabine or autologous HCT predicted higher early
      T-cell chimaerism (P = 0.001), while advanced donor age predicted lower
      chimaerism (P < or = 0.02). Patients with aggressive diseases were at higher risk
      for relapse/disease progression, and shorter progression-free and overall
      survival (P < 0.01). These results suggest that the dosing of certain cellular
      subsets of PBSC products can influence important outcomes post-HCT after non
      myeloablative conditioning.

PMID- 15725089
TI  - Persistence of recipient plasma cells and anti-donor isohaemagglutinins in
      patients with delayed donor erythropoiesis after major ABO incompatible non
      myeloablative haematopoietic cell transplantation.
AB  - Delayed donor erythropoiesis and pure red-cell aplasia (PRCA) complicate major
      ABO mismatched non-myeloablative allogeneic stem-cell transplantation. To
      characterize these events, we analysed red-cell serology and chimaerism in
      lymphohaematopoietic lineages, including plasma cells and B cells, in 12
      consecutive major-ABO incompatible transplants following
      cyclophosphamide/fludarabine-based conditioning. Donor erythropoiesis was delayed
      to more than 100 days in nine (75%) patients including six (50%) who developed
      PRCA. During PRCA, all patients had persistent anti-donor isohaemagglutinins and
      recipient plasma cells (5-42%), while myeloid and T cells were completely donor
      in origin. In contrast, B-cell chimaerism was frequently full-donor when
      significant anti-donor isohaemagglutinins persisted. Four patients with early
      mixed haematopoietic chimaerism and the prolonged presence of anti-donor
      isohaemagglutinins and recipient plasma cells developed delayed-onset (>100 days
      post-transplant) red cell transfusion dependence and PRCA after myeloid
      chimaerism converted from mixed to full donor. These findings confirm that donor
      erythropoiesis is impacted by temporal disparities in donor immune-mediated
      eradication of recipient lymphohaematopoietic cells during major-ABO
      incompatibility and suggest that plasma cells are relatively resistant to graft
      versus-host haematopoietic effects.

PMID- 15725090
TI  - Impact of chimaerism analysis and kinetics on allogeneic haematopoietic stem cell
      transplantation outcome after conventional and reduced-intensity conditioning
      regimens.
AB  - This retrospective study aimed to analyse the impact on overall survival (OS) and
      event-free survival (EFS) of chimaerism status and kinetics following allogeneic
      conventional and reduced-intensity conditioning haematopoietic stem cell
      transplantation, and to compare this with the impact of other well-known factors.
      We investigated the chimaerism status of 187 patients [84 females, 103 males;
      median age 39.5 years (range, 17-62 years)]. After transplantation, 121 patients
      (65%) presented full donor chimaerism (FDC) and 63 (34%) mixed chimaerism (MC).
      For MC, we divided the population into patients who presented regressive mixed
      chimaerism (RMC) (21 patients: 11%), stable mixed chimaerism (SMC) (20 patients:
      11%) and progressive mixed chimaerism (PMC) (22 patients: 12%). At last follow
      up, 71 patients were alive and 116 had died (48% from disease progression and 52%
      from transplant-related causes). With a mean follow-up of 39.4 and 34.8 months,
      the 5-year probabilities of OS and EFS for the total group were, respectively,
      55% and 43%: 69.5% and 61% for FDC, 35.4% and 25% for RMC, 42.6% and 28.6% for
      SMC, and 21% and 10.4% for PMC (P < 0.0001 and P < 0.0001). Multivariate analysis
      only showed a significant impact of chimaerism status on OS, as well as acute and
      chronic graft-versus-host disease on EFS, with a trend for conditioning regimen.

PMID- 15725091
TI  - Pilot study of reduced-intensity conditioning followed by allogeneic stem cell
      transplantation from related and unrelated donors in patients with myelofibrosis.
AB  - A prospective pilot study was performed to evaluate the effect of reduced
      intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and
      anti-thymocyte globulin followed by allogeneic stem cell transplantation from
      related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis.
      The median age of the patients was 53 years (range, 32-63). No primary graft
      failure occurred. The median time until leucocyte (>1.0 x 10(9)/l) and platelet
      (>20 x 10(9)/l) engraftment was 16 (range, 11-26) and 23 d (range, 9-139)
      respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%).
      Acute graft-versus-host disease (GvHD) grades II-IV and III/IV occurred in 48%
      and 19% of cases and 55% of the patients had chronic GvHD. Treatment-related
      mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0-32%] at 1
      year. Haematological response was seen in 100% and complete histopathological
      remission was observed in 75% of the patients and 25% of the patients showed
      partial histopathological remission with a continuing decline in the grade of
      fibrosis. After a median follow-up of 22 months (range, 4-59), the 3-year
      estimated overall and disease-free survival was 84% (95% CI: 67-100%).

PMID- 15725092
TI  - Platelet size deviation width, platelet large cell ratio, and mean platelet
      volume have sufficient sensitivity and specificity in the diagnosis of immune
      thrombocytopenia.
AB  - We investigated the significance of the platelet indices, mean platelet volume
      (MPV), platelet size deviation width (PDW), and platelet-large cell ratio (P
      LCR), in the diagnosis of thrombocytopenia by comparing these levels in 40
      patients with hypo-productive thrombocytopenia (aplastic anaemia; AA) and 39
      patients with hyper-destructive thrombocytopenia (immune thrombo-cytopenia; ITP).
      The sensitivity and specificity of platelet indices to make a diagnosis of ITP
      were also compared. All platelet indices were significantly higher in ITP than in
      AA, and platelet indices showed sufficient sensitivity and specificity. The area
      under the curve (AUC) of the receiver operating characteristics curve of platelet
      indices was large enough to enable the diagnosis of ITP. P-LCR and PDW had the
      largest AUCs, which indicated that these values were very reliable for immune
      thrombocytopenia. Our results suggest that these indices provide clinical
      information about the underlying conditions of thrombocytopenia. More attention
      should be paid to these indices in the diagnosis of thrombocytopenia.

PMID- 15725093
TI  - Difference in absolute risk of venous and arterial thrombosis between familial
      protein S deficiency type I and type III. Results from a family cohort study to
      assess the clinical impact of a laboratory test-based classification.
AB  - Hereditary protein S (PS) deficiency type I is an established risk factor for
      venous thromboembolism. Contradictionary data on type III deficiency suggests a
      difference in risk between both types. We studied 156 first degree relatives (90%
      of eligible relatives) from type I deficient probands (cohort 1) and 268 (88%)
      from type III deficient probands (cohort 2) to determine the absolute risk of
      venous and arterial thromboembolism. Annual incidences of venous thromboembolism
      were 1.47 and 0.17 per 100 person-years in deficient and non-deficient relatives
      in cohort 1 [relative risk (RR) 8.9; 95% confidence interval (CI) 2.6-30.0], and
      0.27 vs. 0.24 in cohort 2 (RR 0.9; 95% CI 0.4-2.2). Type III deficiency was
      demonstrated in 20% of non-deficient relatives in cohort 1 and the annual
      incidence in this subgroup was 0.70 (RR 4.3;0.95-19.0). The cut-off level of free
      PS to identify subjects at risk was 30%, the lower limit of its normal range
      (65%). PS deficiency was not a risk factor for arterial thromboembolism. In
      conclusion, type I deficiency was found to be a strong risk factor for venous
      thromboembolism, in contrast with type III deficiency. This was because of lower
      free PS levels in type I deficient subjects and a free PS cut-off level far below
      the lower limit of its normal range.

PMID- 15725094
TI  - Autocrine secretion of osteopontin results in degradation of I kappa B in Bcr-Abl
      expressing cells.
AB  - Osteopontin has been identified as a marker of metastasis formation and its
      increased expression has been correlated with the malignancy of cancer. In this
      study we provide evidence that increased expression of osteopontin may also be
      associated with progression of Bcr-Abl-expressing leukaemia cells. The Bcr-Abl
      fusion protein, generated by the Philadelphia translocation, is the hallmark of
      chronic myeloid leukaemia (CML). CML exhibits clinically distinct phases.
      Advanced disease shows defective differentiation, bone marrow infiltration and
      drug resistance. The critical signalling mediating this disease progression is
      unknown. Increased aggressiveness of the disease has been correlated with
      elevated amounts of Bcr-Abl. We generated a 32D cell line model to study the
      consequences of different expression levels of Bcr-Abl. Osteopontin was
      identified by microarray analysis as highly upregulated in cells expressing
      elevated amounts of Bcr-Abl. Moreover, in high Bcr-Abl expressing cells, an
      additional 50 kDa isoform of osteopontin was detected. It was found that this
      protein was secreted and that myeloid progenitor cells also expressed appropriate
      receptors for autocrine activation. We demonstrated that secretion of osteopontin
      resulted in enhanced degradation of I kappa B, the inhibitor of NF-kappa B. These
      data indicate a novel consequence of elevated Bcr-Abl expression, which may
      contribute to the progression of CML.

PMID- 15725095
TI  - Heterogeneity of the epsilon gamma delta beta-thalassaemias: characterization of
      three novel English deletions.
AB  - We have characterized three novel epsilon gamma delta beta-thalassaemia deletions
      in three English families. Two of the deletions, 114 and 439 kb, removed the
      entire beta-globin gene complex, including a variable number of flanking
      olfactory receptor (HOR) genes. The 98-kb deletion extended 90-kb upstream of the
      epsilon gene to 8 kb upstream of the G gamma-gene, leaving the gamma,delta and
      beta-genes intact. The 439 kb deletion is the largest deletion reported so far to
      cause epsilon gamma delta beta-thalassaemia; heterozygotes for this deletion were
      variably affected by neonatal haemolytic anaemia. Two of the deletions were de
      novo. Breakpoints of all three deletions occurred within regions of L1 or Alu
      repeats and contained short regions of direct homology between the flanking
      sequences, a feature that is likely to have contributed to the illegitimate
      recombinations.

PMID- 15725096
TI  - Anti-inflammatory and angiostatic therapy in chemorefractory multisystem
      Langerhans' cell histiocytosis of adults.

PMID- 15725097
TI  - Minimal residual disease monitoring in multiple myeloma: flow cytometry is the
      method of choice.

PMID- 15725099
TI  - The Philadelphia translocation and pre-existing myeloproliferative disorders.

PMID- 15725101
TI  - The biology of Malassezia organisms and their ability to induce immune responses
      and skin disease.

PMID- 15725102
TI  - Intradermal testing with the storage mite Tyrophagus putrescentiae in normal dogs
      and dogs with atopic dermatitis in Colorado.
AB  - The purpose of this study was to evaluate reactions to intradermal injections of
      Tyrophagus putrescentiae extract in healthy dogs and dogs with atopic dermatitis
      and to compare the prevalence of positive reactions in the two groups. Twenty-one
      healthy dogs and 26 atopic dogs were tested intradermally with T. putrescentiae
      extract at 1000, 500, 250, 125, 63, 32 and 16 PNU/mL. Reactions were evaluated
      objectively and subjectively. A Mann-Whitney test was used to determine
      differences in grade of reaction to storage mites between healthy dogs and dogs
      with atopic dermatitis. Positive reactions to storage mite extract were most
      common at 1000 PNU/mL with approximately one third of normal and atopic dogs
      showing a positive reaction to T. putrescentiae. There was no significant
      difference in the incidence of positive reactions between normal and atopic dogs
      for any of the Tyrophagus extract concentrations.

PMID- 15725103
TI  - Prevalence of house dust mites and dermatophagoides group 1 antigens collected
      from bedding, skin and hair coat of dogs in south-west England.
AB  - The house dust mites Dermatophagoides farinae (Df) and D. pteronyssinus (Dpt) are
      commonly implicated as allergens causing canine atopic dermatitis in the UK.
      However, there are few studies that characterize the exposure of UK pet dogs to
      these mites. The objectives of this study were to determine the prevalence of the
      mite species on the skin, hair coat and bedding of a population of pet dogs. Dust
      samples (n = 68) were collected from both dogs and their beds using a
      standardized vacuuming technique and stored at -20 degrees C. Mites were
      identified using accepted morphological criteria. House dust mite allergen
      concentrations were assayed using standardized ELISA for Dpt and Df group 1
      allergens (Der p 1 and Der f 1). Mites were identified in 15/68 samples (22%) and
      Dpt was the most common. Df mites were not present. Der p 1 allergens were
      detected in 60% of samples, and Der f 1 in 6% of samples. There were no
      significant differences between the number of Der p 1 positive samples from dogs
      and the number of those from their bedding, or between the average Der p 1
      concentrations from dogs and the number of those from their bedding. Contrary to
      studies elsewhere in Europe and the USA, these findings support studies of human
      asthma patients in the UK, where exposure to Df is rare, but to Dpt is common. As
      the prevalence of positive intradermal and serological reactions to Df in atopic
      dogs is high, further investigations are warranted to clarify true Df
      hypersensitivity or potential immunological cross-reactivity between mite
      allergens.

PMID- 15725104
TI  - Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological
      study.
AB  - Ten Chesapeake Bay retriever (CBRS) dogs with hair loss were recruited in
      collaboration with the American Chesapeake Club. All dogs had nonpruritic,
      noninflammatory, regionalized hair loss affecting the same areas of the body in
      male and female dogs. Hormonal investigations showed increased adrenal and sex
      steroid concentration in seven cases. Histopathology revealed follicular
      hyperkeratosis and plugging, follicular atrophy, and occasional melanin clumping
      with malformed hair shafts. This study suggests that hair loss in CBRS is a breed
      syndrome in which young adult dogs have hair loss characterized by unusual
      histological features and abnormal steroid production. A familial predisposition
      seems likely and selective breeding might reduce the occurrence of this
      condition.

PMID- 15725105
TI  - Bacteria and fungi on the surface and within noninflamed hair follicles of skin
      biopsy specimens from horses with healthy skin or inflammatory dermatoses.
AB  - A retrospective study using light microscopy was performed to assess the
      prevalence of surface and follicular bacteria and fungi in skin biopsy specimens
      from 247 horses with inflammatory dermatoses and from 27 horses with healthy
      skin. Cocci were found on the surface of specimens from 23% (95% confidence
      interval 18%, 29%) and 7% (95% confidence interval, 0%, 19%), respectively, of
      horses with skin disease and horses with healthy skin. Of the nine dermatoses
      with at least 10 cases in our series of horses, bacterial folliculitis had a
      higher prevalence of surface bacteria (57%; 95% confidence interval 34%, 81%)
      than the other eight (which all had a prevalence < 30%). There was a significant
      association between the prevalence of surface cocci and the extent of epidermal
      hyperkeratosis. Cocci were found in the keratin of noninflamed hair follicles in
      only 2% of the horses with skin disease, and in none of the horses with healthy
      skin. Fungal poroconidia were found on the surface of 4% of the horses with skin
      disease, and on none of the horses with healthy skin. Yeasts were not found.

PMID- 15725106
TI  - Treatment of localized lesions of canine atopic dermatitis with tacrolimus
      ointment: a blinded randomized controlled trial.
AB  - This investigator-blinded randomized controlled trial was designed to determine
      whether tacrolimus ointment (Protopic, Fujisawa Healthcare) decreased the
      severity of localized lesions of canine atopic dermatitis (AD). Twenty dogs with
      AD were enrolled if they exhibited lesions on both front metacarpi. Each foot was
      randomized to be treated with 0.1% tacrolimus or placebo (vaseline) ointment
      twice daily for 6 weeks. Before, and every 2 weeks during the study, erythema,
      lichenification, oozing and excoriations each were graded on a 10-point scale
      (maximal total score: 40). The primary outcome measures were the percentage
      reduction from baseline of lesional scores and the number of subjects whose
      scores had decreased by 50% or greater at study end. Intention-to-treat analyses
      were used. At study onset, lesional scores were not significantly different
      between sites treated with tacrolimus or placebo. After 6 weeks, the percentage
      reduction from baseline scores was higher for tacrolimus-treated sites (median:
      63%; 95% confidence interval: 39-67) than for placebo-treated feet (median: 3%;
      confidence interval: -2-13) (Wilcoxon test; P = 0.0003). When tacrolimus was
      applied, lesions decreased by 50% or greater in 15/20 dogs (75%); these dogs were
      those that completed the study. In contrast, this benchmark was not reached for
      any placebo-treated feet (Fisher's test; P < 0.0001). Adverse drug events
      consisted of minor irritation in some lesional areas treated with tacrolimus.
      Results of this trial suggest that the application of 0.1% tacrolimus ointment is
      useful for reducing the severity of localized skin lesions of canine AD.

PMID- 15725108
TI  - Junctional epidermolysis bullosa in two domestic shorthair kittens.
AB  - This article describes two cases of junctional epidermolysis bullosa in
      nonrelated kittens. Both cats exhibited pinnal erosions, oral ulcerations and
      severe onychomadesis. Histopathology, electron microscopy and/or indirect
      immunoperoxidase revealed subepidermal clefting, with the lamina densa remaining
      attached to the floor of the vesicles. Indirect immunofluorescence revealed
      reduced staining for laminin-5 gamma2 subunit in case 1 and beta3 subunit in case
      2.

PMID- 15725107
TI  - Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific
      immunotherapy of dogs with refractory atopic dermatitis - a pilot study.
AB  - This pilot study evaluated the effects of immunostimulatory liposome-plasmid-DNA
      complexes combined with specific allergens for immunotherapy of refractory canine
      atopic dermatitis. Seven dogs with previously diagnosed atopic dermatitis and
      unsatisfactory response to at least 12 months of conventional allergen-specific
      immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6,
      10 and 14), with patient-specific allergen extracts contained in cationic
      liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue
      scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent
      and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14.
      Canine cytokine mRNA expression in peripheral blood mononuclear cells collected
      prior to treatment and at the completion of the study was determined for IFN
      gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription
      competitive polymerase chain reaction. Repeated intradermal injections of
      specific allergens incorporated into liposome-nucleic acid complexes were well
      tolerated in all seven dogs. There was a significant improvement in pruritus
      scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P =
      0.0428) at the completion of the trial compared to pretreatment values.
      Medication scores, CADESI and production of other cytokines did not change
      significantly with treatment. These early results suggest that antigen-specific
      immunotherapy using a novel liposome-nucleic acid complex vaccine may be
      beneficial for treatment of established atopic dermatitis in dogs using lower
      antigen doses. Further investigations in larger numbers of dogs with earlier
      stages of disease are warranted.

PMID- 15725109
TI  - Calcinosis involving multiple paws in a cat with chronic renal failure and in a
      cat with hyperthyroidism.
AB  - Calcinosis of multiple paws is described in two cats. A metastatic pathogenesis
      was supported by the laboratory findings of hyperphosphataemia and a calcium x
      phosphorus solubility product > 7 g/L. Hyperparathyroidism could not be confirmed
      because a valid feline parathyroid hormone assay was not available at the time.
      One cat was diagnosed with chronic renal failure and presented initially with an
      irregular nodular calcification on the chin. Dietary and medical management was
      unsuccessful and ultimately the animal was euthanased. Hyperthyroidism was
      diagnosed in another cat by laboratory findings and scintigraphic imaging. In
      addition, the cat had a hyperphosphataemia in the absence of azotaemia.
      Intravenous administration of radioactive iodine as (131)I was accompanied by
      reduction and normalization in serum total thyroxine and phosphorus
      concentrations and resulted in resolution of calcification in the paws.

PMID- 15725110
TI  - Risk assessment: controversies and management of moderate- to high-risk
      individuals.
AB  - With the current understanding of sporadic and familial breast cancer, it is now
      possible to identify individuals who have a moderate or high risk of breast
      cancer. For these individuals, it is useful to perform formal cancer risk
      assessment and develop an individualized risk reduction plan, including a
      tailored plan for cancer screening, preventive therapy, and/or prophylactic
      surgery. Assessment using a predictive model such as the Gail model is
      particularly useful in individuals at increased risk for sporadic breast cancer.
      In addition, assessment of risk based on histologic appearance of benign or
      premalignant breast lesions can be used to identify individuals for whom more
      aggressive risk reduction strategies are warranted. For individuals who are at
      risk for familial cancer syndromes, other predictive models are more appropriate.
      For this extremely high-risk group, genetic testing for mutations in familial
      cancer susceptibility genes is helpful to identify individuals who would benefit
      from even more aggressive cancer risk reduction strategies. Strategies to
      identify the levels of risk for breast cancer, including the identification of
      moderate, high, or very high risk groups are discussed. Management options for
      these groups are presented, including who to consider for more aggressive
      screening, chemoprevention, or prophylactic surgery. Current recommendations for
      screening, chemoprevention, and surgery for each risk group are presented. The
      ability to identify individuals at high risk for breast cancer now enables
      clinicians to intervene to reduce the risk of breast cancer. Aggressive
      screening, preventive therapy, and prophylactic surgery in moderate- to high-risk
      individuals should, in the future, significantly reduce the incidence of invasive
      breast cancer.

PMID- 15725111
TI  - Integrate, innovate, imitate: surviving and thriving in the world of breast
      cancer economics.
AB  - The pursuit of excellence in the breast care delivery process involves a program
      of integration, innovation, and imitation designed to yield sustained quality and
      economic improvement. Many stand-alone breast centers in the United States have
      adopted this approach and have become financially successful while delivering
      very high quality care. This article reviews basic economic principles governing
      breast care as a business enterprise. It then provides recommendations for the
      development of world-class breast centers that can also deliver financially
      responsible care.

PMID- 15725112
TI  - Applying innovations in surgical and radiation oncology to breast conservation
      therapy.
AB  - A paradigm shift is occurring in the radiotherapeutic management of early breast
      carcinoma. The current change includes technological advances in radiation
      therapy delivery to limit toxicity by minimizing patient treatment. These
      treatments include improved techniques for whole-breast irradiation, for example,
      hypofractionation and intensity modulated radiation therapy, and those for
      irradiating a smaller portion of the breast in a shorter period of time,
      specifically, accelerated partial breast irradiation. This article also addresses
      interesting research on delivering radiation therapy intraoperatively and looks
      ahead toward applications aimed at minimizing the physical, biological, and
      psychosocial impact of breast conservation therapy.

PMID- 15725113
TI  - Screening mammography controversies: resolved, partly resolved, and unresolved.
AB  - Since the 1960s, multiple randomized clinical trials have measured differences in
      breast cancer mortality between women 40 and 70 years of age who were offered
      screening mammography and control group women. This article describes briefly
      these trials, which nearly universally documented statistically significant
      reductions in breast cancer deaths. These trials also underestimated the benefit,
      regardless of age, due to screening parameters that were not optimized. In recent
      years, published articles analyzing studies of Swedish women have claimed that
      there is no reduction in overall mortality from breast cancer and other causes
      among women offered screening. Critical assessment of these articles noted that
      breast cancer deaths were less than 5% of all deaths and that no statistically
      significant reduction in overall mortality rates should be expected within the
      population that had been analyzed. The latest screening mammography controversies
      involve potential adverse consequences and risks, such as X-ray exposure,
      detection of ductal carcinoma in situ (DCIS), and "excessive" callback rates for
      additional imaging studies. Despite these controversies, the preponderance of
      scientific evidence continues to strongly support annual screening mammography
      for women 40 years of age and older.

PMID- 15725114
TI  - Targeted therapies in breast cancer.
AB  - Targeted therapeutic agents in breast cancer are representing a larger proportion
      of new drugs entering clinical testing. Carcinogenesis is a multistep process
      characterized by genetic alterations that influence key cellular pathways
      involved in growth and development. Therefore, there are numerous opportunities
      for pharmacologic targeting. Hormonal therapy is the prototype of a treatment
      targeting hormone receptors, and this class of drugs still provides the greatest
      overall impact on outcome. Even though chemotherapy is considered a cytotoxic and
      nonspecific therapy, it does modulate many key cellular pathways and therefore
      shares characteristics of biologic drugs. It is clear that targeted therapies are
      going to play a greater role in improving survival and quality of life in
      advanced breast cancer, with trastuzumab (Herceptin) serving as a successful
      model that is a relatively nontoxic agent associated with survival benefits.
      However, several challenges to the successful identification and application of
      therapeutic targets remain. These include the dissection of complicated and
      interacting biologic pathways and the limitations of preclinical models that will
      allow for a better prioritization of which drugs and combinations will succeed
      best in the clinic. Better methods for selecting ideal candidates for therapy
      need to be based on known modes of action. Mechanisms of intrinsic and acquired
      resistance need further exploration in order to refine drug design. Toxicities
      that might result from modulation of the targeted pathway must be expected and
      fully characterized. Some biologic strategies may need to be tested in less
      refractory cases, or even in early stages, even though this may be more costly
      and could raise safety concerns. Fortunately progress in all of these areas is
      expected with the availability of new technologies and a growing infrastructure
      for preclinical and clinical testing.

PMID- 15725117
TI  - Abstracts of the TSANZ and ANZSRS Annual Scientific Meeting. March 18-23, 2005.
      Perth, Australia.

PMID- 15725119
TI  - Radon track imaging in CR-39 plastic detectors using confocal scanning laser
      microscopy.
AB  - Confocal scanning laser microscopy (CSLM) has been used to provide the first
      images of radon track populations in two external CR-39 plastic detectors.
      Measurements of variables including track area distribution and estimates of the
      angle of track inclination (dip) derived from surface CSLM sections are
      presented. CSLM depth slices, combined with three-dimensional (3D) visualization
      techniques, provide a new, non-destructive way of examining the 2D and 3D
      geometry of the etched tracks within solid-state nuclear track detectors that may
      prove useful in complementing existing optical microscopy methods.

PMID- 15725116
TI  - Are there downsides to mammography screening?
AB  - Most Americans clearly believe that routine screening mammography is beneficial.
      Given its widespread acceptance, it is useful to consider what the downsides of
      mammography screening are so that patients are fully informed in the decisions
      they make. This article lists some less well-recognized risks of mammography,
      such as false negatives and their accompanying false reassurance, as well as the
      direct and indirect costs to women and society. Three important downsides
      radiation hazard, overdiagnosis of breast cancer, and the paradoxical increase in
      breast cancer mortality observed in screened women compared to controls age 40-49
      years-are addressed. The article also considers the reasons that women are poorly
      informed about the downsides of mammography. There is, however, agreement that
      early diagnosis and treatment are important, and that new methods to reduce
      breast cancer deaths must be sought.

PMID- 15725120
TI  - Simple optimization procedure for objective lens correction collar setting.
AB  - We present a new method for setting a coverglass correction collar on an
      objective lens. Axial scans across the interface between the specimen volume and
      the slide are used together with a quantitative function of merit to determine
      the optimum setting of the correction collar. The method, which simplifies the
      adjustment for the user and reduces photobleaching, was implemented within the
      software environment of a scanning microscope system.

PMID- 15725121
TI  - Waveguide sidewall roughness measurement on full wafers by SEM-based stereoscopy.
AB  - We present a technique aiming at sidewall roughness measurement on integrated
      optical silica waveguides using a scanning electron microscope. The technique
      uses the principles of stereoscopy to retrieve sidewall topography. Practical
      implementation details and first results are provided.

PMID- 15725122
TI  - Imaging the substructure of antibodies with tapping-mode AFM in air: the
      importance of a water layer on mica.
AB  - Monoclonal antibodies (immunoglobulin G; IgG) against the N-terminal domain of
      the A subunit of DNA gyrase have been imaged using tapping-mode atomic force
      microscopy under ambient conditions on hydrophilic mica surfaces. The familiar
      tri-nodal submolecular resolution of IgG (i.e. 50-kDa resolution) has been
      achieved when operating the microscope with the tip predominantly in the
      attractive force regime. Under common laboratory conditions of about 40% relative
      humidity, the resolution of this substructure was not achieved owing to motion of
      the antibodies on the surface and/or image distortion from tip-sample
      instabilities. Reproducible imaging of the tri-nodal antibody substructure was
      achieved by desiccating the samples for extended periods of time (1 week or more)
      before imaging. This effect is attributed to the presence of a humidity-dependent
      thin water layer (a few molecules or nanometres thick), which has been observed
      previously using the surface force apparatus and scanning polarization force
      microscopy. Desiccation of the mica surfaces allowed enough water to be removed
      from the mica surface to prevent this effect. Degradation in the image quality
      over the imaging period of an hour or two was observed, owing to re-adsorption of
      water under the ambient laboratory conditions.

PMID- 15725123
TI  - Two-photon excitation and emission spectra of the green fluorescent protein
      variants ECFP, EGFP and EYFP.
AB  - Summary Two-photon (TP) excitation (820-1150 nm) and emission (280-700 nm)
      spectra for the fluorescent proteins (FPs) ECFP3, EGFP3 and EYFP3 produced in
      human tumour cells were recorded. TP excitation spectra of pure and highly
      enriched samples were found to be more differentiated in comparison with their
      one-photon (OP) spectra. They exhibited more pronounced main and local maxima,
      which coincided among different purity grades within small limits. TP and OP
      emission spectra of pure and enriched samples were identical. However, in crude
      samples, excitation was slightly blue-shifted and emission red-shifted. The data
      indicate that both OP and TP excitation routes led to the same excited states of
      these molecules. The emission intensity is dependent on the pH of the environment
      for both types of excitation; the emission intensity maximum can be recorded in
      the alkaline range. Reconstitution of emission intensity after pH quenching was
      incomplete, albeit that the respective spectral profiles were identical to those
      prequenching. When emission data were averaged over the whole range of
      excitation, the resulting emission profile and maximum coincided with the data
      generated by optimal excitation. Therefore, out-of-maximum excitation, common
      practice in TP excitation microscopy, can be used for routine application.

PMID- 15725124
TI  - Third-order aberration theory of Wien filters for monochromators and aberration
      correctors.
AB  - Third-order aberrations at the first and the second focus planes of double focus
      Wien filters are derived in terms of the following electric and magnetic field
      components--dipole: E1, B1; quadrupole: E2, B2; hexapole: E3, B3 and octupole:
      E4, B4. The aberration coefficients are expressed under the second-order
      geometrical aberration free conditions of E2 = -(m + 2)E1/8R, B2 = -mB1/8R and
      E3R2/E1 - B3R2/B1 = m/16, where m is an arbitrary value common to all equations.
      Aberration figures under the conditions of zero x- and y-axes values show very
      small probe size and similar patterns to those obtained using a previous
      numerical simulation [G. Martinez & K. Tsuno (2004) Ultramicroscopy, 100, 105
      114]. Round beam conditions are obtained when B3 = 5m2B1/144R2 and (E4/E1 -
      B4/B1)R3 = -29m2/1152. In this special case, aberration figures contain only
      chromatic and aperture aberrations at the second focus. The chromatic aberrations
      become zero when m = 2 and aperture aberrations become zero when m = 1.101 and
      10.899 at the second focus. Negative chromatic aberrations are obtained when m <
      2 and negative aperture aberrations for m < 1.101. The Wien filter functions not
      only as a monochromator but also as a corrector of both chromatic and aperture
      aberrations. There are two advantages in using a Wien filter aberration
      corrector. First, there is the simplicity that derives from it being a single
      component aberration correction system. Secondly, the aberration in the off-axis
      region varies very little from the on-axis figures. These characteristics make
      the corrector very easy to operate.

PMID- 15725125
TI  - The use of rhodamine 6G and fluorescence microscopy in the evaluation of
      phospholipid-based polymeric biomaterials.
AB  - A technique is described that allows the staining and subsequent visualization of
      polymers that contain the phosphorylcholine (PC) group. These materials are
      useful as bulk materials or coatings for the fabrication of medical devices. The
      staining method employs rhodamine 6G, which can be simply and rapidly applied to
      the polymer coating and imaged using fluorescence microscopy. The specificity of
      the staining for the PC polymers makes this technique suitable for the evaluation
      of a wide range of substrates and provides qualitative information on coating
      uniformity, coverage and morphology. It can be used to examine the durability of,
      and defects in, the coating. Statistical analysis of the fluorescent intensity by
      measuring the pixel value during imaging can allow for the method to be used as a
      quality control tool.

PMID- 15725126
TI  - Characterization of ultrafine coal fly ash particles by energy-filtered TEM.
AB  - In this study, energy-filtered transmission electron microscopy is demonstrated
      to be a valuable tool for characterizing ultrafine coal fly ash particles,
      especially those particles encapsulated in or associated with carbon. By
      examining a series of elemental maps (K-edge maps of C and O, and L-edge maps of
      Si, Al, Ti and Fe) recorded using the three-window method, considerable numbers
      of titanium and iron species with sizes from several nanometres to submicrometre
      were shown to be present, typically as oxides dispersed in the carbonaceous
      matrix. Crystalline phases, such as rutile and iron-rich oxide spinel, were also
      identified from electron diffraction patterns and high-resolution TEM images.
      Information about these ultrafine coal fly ash particles regarding their size,
      morphology, elemental composition and distribution, and crystalline phases, which
      has not been available previously in conventional ash studies, should be useful
      in toxicological studies and related environmental fields.

PMID- 15725127
TI  - New technique for in-situ measurement of backscattered and secondary electron
      yields for the calculation of signal-to-noise ratio in a SEM.
AB  - The quality of an image generated by a scanning electron microscope is dependent
      on secondary emission, which is a strong function of surface condition. Thus,
      empirical formulae and available databases are unable to take into account actual
      metrology conditions. This paper introduces a simple and reliable measurement
      technique to measure secondary electron yield (delta) and backscattered electron
      yield (eta) that is suitable for in-situ measurements on a specimen immediately
      prior to imaging. The reliability of this technique is validated on a number of
      homogenous surfaces. The measured electron yields are shown to be within the
      range of published data and the calculated signal-to-noise ratio compares
      favourably with that estimated from the image.

PMID- 15725128
TI  - Structural characterization of TiN/NbN multilayers: X-ray diffraction, energy
      filtered TEM and Fresnel contrast techniques compared.
AB  - Two TiN/NbN multilayers with wavelength 13.6 and 6.15 nm have been characterized
      by X-ray diffraction (XRD), Fresnel contrast analysis (FCA) and energy-filtered
      transmission electron microscopy (EFTEM). Good agreement between the composition
      profile obtained by FCA and EFTEM is obtained if the lower resolution of the
      EFTEM images is taken into account. The relative advantages and disadvantages of
      the techniques are discussed. Used together the two TEM techniques provide a
      quantitative characterization that is consistent with, and for some parameters
      provides more precise values than, that from XRD. The analysis shows that the
      multilayers have narrow interfaces (< 1 nm) and a composition amplitude close to
      95% for the longer wavelength.

PMID- 15725129
TI  - Two-photon excitation fluorescence pH detection using 2,3-dicyanohydroquinone: a
      spectral ratiometric approach.
AB  - The use of 2,3-dicyanohydroquinone (DCHQ) as an emission ratiometric probe of pH
      in vitro and in fibroblast cells was evaluated using two-photon excitation
      fluorescence microscopy (TPEFM). In addition, methods for spectrally calibrating
      the Zeiss LSM510 META spectroscopy system for TPEFM were also developed. The
      emissions of both the acid and base forms of DCHQ were detectable when using an
      800-nm excitation in TPEFM, thereby allowing ratiometric determination of pH.
      These data suggest that, in contrast to most other emission ratiometric probes,
      both acid and base forms of DCHQ have similar two-photon cross-sectional areas at
      800 nm. Acid (maximum at approximately 457 nm) and base (maximum at approximately
      489 nm) DCHQ TPEFM emission spectra were similar to previously reported one
      photon excitation emission spectra. Calibration curves for pH were successfully
      constructed using the ratio of DCHQ emission difference maxima at 460 nm and 512
      nm in vitro and in cells. To our knowledge, DCHQ is currently the only effective
      emission ratiometric pH indicator for two-photon microscopy and may serve as a
      useful starting point for the development of other TPEFM ratiometric dyes for
      quantitative measurement of other cell parameters such as Ca2+, Mg2+ or Na+.

PMID- 15725130
TI  - A simple method allowing DIC imaging in conjunction with confocal microscopy.
AB  - Current optical methods to collect Nomarski differential interference contrast
      (DIC) or phase images with a transmitted light detector (TLD) in conjunction with
      confocal laser scanning microscopy (CLSM) can be technically challenging and
      inefficient. We describe for the first time a simple method that combines the use
      of the commercial product QPm (Iatia, Melbourne Australia) with brightfield
      images collected with the TLD of a CLSM, generating DIC, phase, Zernike phase,
      dark-field or Hoffman modulation contrast images. The brightfield images may be
      collected at the same time as the confocal images. This method also allows the
      calculation of contrast-enhanced images from archival data. The technique
      described here allows for the creation of contrast-enhanced images such as DIC or
      phase, without compromising the intensity or quality of confocal images collected
      simultaneously. Provided the confocal microscope is equipped with a motorized z
      drive and a TLD, no hardware or optical modifications are required. The contrast
      enhanced images are calculated with software using the quantitative phase
      amplitude microscopy technique (Barone-Nugent et al., 2002). This technique,
      being far simpler during image collection, allows the microscopist to concentrate
      on their confocal imaging and experimental procedures. Unlike conventional DIC,
      this technique may be used to calculate DIC images when cells are imaged through
      plastic, and without the use of expensive strain-free objective lenses.

PMID- 15725131
TI  - A method for automated detection of gene expression required for the
      establishment of a digital transcriptome-wide gene expression atlas.
AB  - Acquiring information about the expression of a gene in different cell
      populations and tissues can provide key insight into the function of the gene. A
      high-throughput in situ hybridization (ISH) method was recently developed for
      rapid and reproducible acquisition of gene expression patterns in serial tissue
      sections at cellular resolution. Characterizing and analysing expression patterns
      on thousands of sections requires efficient methods for locating cells and
      estimating the level of expression in each cell. Such cellular quantification is
      an essential step in both annotating and quantitatively comparing high-throughput
      ISH results. Here we describe a novel automated and efficient methodology for
      performing this quantification on postnatal mouse brain.

PMID- 15725132
TI  - A comparison of 250 and 500 mL of terminal warm blood cardioplegia after global
      myocardial ischemia: a prospective randomized study.
AB  - BACKGROUND: Controlled reperfusion with terminal warm blood cardioplegia (TWBC)
      improves myocardial performance after global ischemia. However, the optimum
      volume required is unknown. METHODS: Fifty patients undergoing elective coronary
      artery bypass graft surgery were prospectively randomized to receive either 250
      or 500 mL of TWBC. During TWBC delivery, and for 10 minutes after cross-clamp
      removal, samples were taken from the aorta and coronary sinus to measure the
      hydrogen ion, lactate, and oxygen content. RESULTS: At the end of TWBC delivery,
      the 500 mL group had significantly less hydrogen ion washout (p = 0.006) compared
      with the 250 mL group. Also, more hydrogen ions (p = 0.02) and lactate (p = 0.02)
      had been washed out during the entire period of TWBC delivery in the 500 mL group
      compared with the 250 mL, indicating better metabolic recovery. By 4 minutes
      after aortic cross-clamp removal, hydrogen ion and lactate washout, as well as
      oxygen extraction was similar in the two groups. However, the time to return to
      regular mechanical activity was prolonged in the 500 mL group, 5.8 (3) versus 4.6
      (3) minutes in the 250 mL group (p = 0.05). Though there was no difference in
      postoperative Troponin T levels, eight patients in the 500 mL group versus four
      in the 250 mL group required ionotropic support (p = 0.1). CONCLUSIONS: A total
      of 500 mL of hotshot achieves a better metabolic state after hotshot delivery.
      However, there is no clinical benefit or improvement in the postoperative
      Troponin T release suggesting that in a short ischemic time, 500 mL TWCB has a
      limited clinical benefit.

PMID- 15725133
TI  - Multivessel off-pump revascularization in patients with significant left main
      coronary artery stenosis: early and midterm outcome analysis.
AB  - BACKGROUND: The presence of significant left main stenosis (> or =50%) has been
      considered a relative contraindication to the use of off-pump coronary artery
      bypass (OPCAB) stemming from well-documented hemodynamic perturbations during the
      displacement of the heart. We examined our experience with patients with critical
      left main stenosis (LMS) to assess the safety and feasibility of OPCAB in this
      subgroup. METHODS: Our prospectively updated database was queried to identify all
      patients with severe left main disease who underwent isolated coronary
      revascularization between January 1, 1999 and May 31, 2002. This query yielded
      234 on-pump and 420 off-pump patients with significant LMS whose clinical
      information was retrospectively reviewed. RESULTS: The groups were well matched
      with regard to gender, left ventricular function, surgical priority, and severity
      of angina. The conventional coronary artery bypass (CABG) group was significantly
      younger than the OPCAB group and had a higher incidence of a previous myocardial
      infarction. Patients in the CABG cohort were more likely than OPCAB patients to
      remain ventilated after 24 hours, require placement of intraoperative or
      postoperative intraaortic balloon pump, or suffer from postoperative renal
      failure. There was a decrease in mortality (6.4% vs. 1.9%; p = 0.006) when CPB
      was eliminated. Intermediate term survival analysis revealed a significant
      survival benefit in the off-pump group (p = 0.007). CONCLUSIONS: Multivessel off
      pump revascularization in patients with severe left main disease is a safe and
      effective alternative to conventional bypass grafting and conveys a survival
      benefit.

PMID- 15725134
TI  - Long-term outcome after total correction of tetralogy of Fallot in adolescent and
      adult age.
AB  - Although most patients with tetralogy of Fallot (TOF) undergo radical repair
      during infancy and childhood, patients remaining undiagnosed and untreated until
      adulthood can still be treated. These patients have either a previous palliative
      or natural collateral circulation to the lung or a mild form of right ventricular
      outflow tract (RVOT) obstruction. The aim of this study is to analyze the
      perioperative and long-term results of radical corrective procedures in patients
      who reached adult ages. Two hundred and seven patients with TOF underwent
      complete correction between 1985-and 2002, 64 (30.9%) of whom were aged 14 years
      or more. The mean age at corrective repair for this group was 20.6 +/- 7.5 years
      (range 14 to 49 years). Only two patients had previous modified Blalock-Taussig
      shunts. In 44 patients (68.7%) besides infundibular resection, a transannular
      gluteraldehyde-treated pericardial patch was used to reconstruct right
      ventricular outflow tract (RVOT). Only infundibular patching was used in 15
      patients (23.4%) and infundibular muscular resection with primary closure of
      right ventricle was performed in five patients (7.8%). Hospital mortality was
      3.1% with two patients. Four patients (6.2%) underwent reoperation because of
      recurrent ventricular septal defect (VSD) with/without residual obstruction or
      pulmonary regurgitation. All survivors were in NYHA class I (42) or II (17). Late
      mortality was recorded in two patients and 16-year actuarial survival was 89.2%+/
      4.9%. The significant negative predictors of late survival determined by
      univariate analysis were reoperation <0.018) and associated cardiac anomalies
      <0.011). Multivariate analysis showed that there was no negative predictor of
      late-term mortality. Corrective procedures in adult patients with TOF can be
      performed successfully compared to patients who underwent operation during
      infancy and childhood.

PMID- 15725135
TI  - Are discrete coronary artery fistulae different from coronary arteriovenous
      malformations?
AB  - AIM: To delineate whether coronary arteriovenous malformations have different
      properties than classical discrete coronary artery fistulae. METHODS: Group 1
      included 17 patients with discrete coronary fistula that represents a coronary
      artery fistula draining into any cardiac chamber. Group 2 included six patients
      with coronary arteriovenous malformations representing extensive coronary artery
      malformation. Cardiopulmonary bypass was used in 12 of the Group 1 patients and 5
      in Group 2. RESULTS: There was no operative mortality in either group. Following
      a hemodynamically nonsignificant residual fistulous communication, which was
      detected by repeat coronary angiography in Group 2; we changed our surgical
      technique of suture ligation on beating heart. Then we preferred pulmonary
      arteriotomy and sutured the orifice of coronary arteriovenous malformations from
      within the chamber. CONCLUSIONS: Coronary arteriovenous malformations have
      different morphology and also complex progression properties when compared with
      discrete coronary artery fistulae. Surgical repair of coronary arteriovenous
      malformation should be done by suturing the multiple drainage holes inside the
      draining chamber. Suture ligation of coronary arteriovenous malformation is
      difficult due to the fragile vessel.

PMID- 15725136
TI  - Determination of troponin I release after CABG surgery.
AB  - BACKGROUND: Troponin I is used to diagnose myocardial infarction (MI). Its use
      and pattern of elevation is not well defined in coronary artery bypass graft
      (CABG) surgery. This study assessed the timing of troponin I elevation in
      patients undergoing urgent CABG. METHOD: Patients undergoing urgent isolated-CABG
      with cardiopulmonary bypass were studied prospectively. Blood samples were taken
      to measure CK, CK-MB, and troponin I: preoperatively, 7 hours postoperatively, 14
      to 18 hours postoperatively, 30 to 48 hours postoperatively, and on postoperative
      day 4. Electrocardiograms and in-hospital course were recorded. Perioperative MI
      (PMI) was defined by either (i) ECG criteria of new Q-waves in the presence of CK
      MB elevation >50 microg/L or (ii) CK-MB > 100 microg/L. RESULTS: Of the 50
      patients studied, 6 met the criteria for PMI (12%); 2 by criteria (i) and 4 by
      criteria (ii). In patients not meeting the criteria for MI the troponin I level
      peaked at 7 hour post-op with a mean of 20.97 microg/L (95% CI, 17.11 to 24.83).
      At this time, patients who met the criteria for MI had a mean troponin I level of
      46.85 microg/L (95% CI, 36.40 to 57.30). Of variables investigated for the 44
      patients who did not meet MI criteria, only preoperative troponin I level
      impacted peak postoperative troponin I. CONCLUSIONS: CABG elevates troponin I far
      beyond current diagnostic benchmarks without the clinical occurrence of a MI and
      appears to peak during the second postoperative day. An elevated preoperative
      troponin I may predict an elevated peak postoperative troponin I in patients who
      do not have a PMI.

PMID- 15725137
TI  - Can revascularization restore sinus rhythm in patients with acute onset
      atrioventricular block?
AB  - BACKGROUND: We studied patients with coronary artery disease (CAD) and complete
      atrioventricular (AV) block of acute onset that were treated with coronary artery
      bypass grafting (CABG) to see whether revascularization can restore the sinus
      rhythm. METHODS: CABG was performed on eight patients with newly developed
      complete AV block and severe CAD. The distribution of coronary artery lesions
      showed a type IV pattern in six patients and a type II pattern in two patients.
      Complete revascularization was performed in six patients. Left anterior
      descending artery was revascularized in all eight patients. The patients were
      followed-up after operation for approximately 10 days before the implantation of
      a permanent pacemaker to see if they recover from AV block. RESULTS: The mean
      interval from development of complete AV block to operation was 3.63 +/- 1.3
      days. There was no operative and/or early mortality. None of the patients
      recovered from complete AV block after coronary revascularization. Early
      morbidity was not detected. The mean hospital stay (12.75 +/- 1.49 days) and
      intensive care unit stay (30.25 +/- 19.39 hours) were relatively long because of
      the delay in permanent pacemaker implantation. All patients were asymptomatic at
      the end of their follow-up period (23.38 +/- 18.41 months). CONCLUSIONS:
      Preoperatively developed complete AV block did not adversely affect the operative
      and early postoperative outcome of CABG operations. Recovery from complete AV
      block cannot be achieved by coronary revascularization performed 3.63 +/- 1.3
      days after the onset of complete AV block.

PMID- 15725138
TI  - Timing of chest tube removal after coronary artery bypass surgery.
AB  - AIM: Assessing the impact of chest tube removal timing following a coronary
      artery bypass grafting surgery on the clinical outcome. METHODS: Eighty-three
      consecutive patients were randomly assigned to either have the chest tube removed
      24 hours (Group A) or 48 hours (Group B) postoperatively. Chest tubes were
      removed on the condition that drainage was less than 100 cc for the last 8 hours.
      Pre- and postoperative data were analyzed. RESULTS: The following preoperative
      and intraoperative risk factors were more prevalent among Group A patients:
      previous MI (60.5% vs 40.7%, p = 0.11), previous CVA (9.1% vs 0%, p = 0.11),
      hypertension (72.7% vs 55.6%, p = 0.14), pump time (111.6 min vs 96.8 min, p =
      0.07), and cross-clamp time (73.8 min vs 64.4 min, p = 0.07). Postoperatively,
      there was a lower demand for analgesics in Group A (2.1 times for 12 hours at 36
      hours vs 3.6 p = 0.09), lower white blood cell count (10,947 at 48 hours vs
      11,576, p = 0.39) a higher oxygen saturation (91.9% at 48 hours vs 88.9%, p =
      0.07), higher expiratory volumes (594 mL at 36 hours vs 514 mL p = 0.08) and
      earlier mobilization (23% walking at 48 hours vs 4%, p = 0.01). Pleural effusion
      and atelectasis were less frequent in Group A in both chest X-rays (66% vs 73%, p
      = 0.6 and 64% vs 75%, p = 0.47, respectively) and CT scans (19% vs 41%, p = 0.1
      and 84% vs 96%, p = 0.42, respectively). There was no difference between the two
      groups in the prevalence of serous wound discharge and the length of hospital
      stay and there were no reported cases of pneumonia throughout the study.
      CONCLUSION: In cases where no excessive drainage accumulates, early removal of
      the chest tubes was found to be a policy that improves the postoperative outcome
      and decreases the need for supportive treatment such as analgetics,
      physiotherapy, nurse care, and oxygen. This policy did not involve significant
      residual effusions.

PMID- 15725139
TI  - Hemodynamic and transesophageal echocardiographic analysis of global and regional
      myocardial functions, before and immediately after coronary artery bypass
      surgery.
AB  - AIM: We investigated the effect of coronary artery bypass grafting (CABG) surgery
      on global and regional myocardial function; before and immediately after coronary
      artery bypass grafting and 1 month after the operation. METHODS: Twenty-five
      patients who were undergoing elective CABG were evaluated. Transesophageal
      echocardiography (TEE) was used to evaluate both global and regional myocardial
      function. Intraoperative TEE images of the left ventricle were obtained after
      cannulation but before cardiopulmonary bypass (CPB), 5 and 30 minutes after the
      termination of CPB. Same time, hemodynamic parameters were recorded.
      Transesophageal echocardiography evaluation was repeated one month after the
      operation. RESULTS: Global left ventricular function was significantly depressed
      5 minutes after CPB. At the 30 minutes after CPB, left ventricular function has
      returned to pre-CPB baseline levels. Global left ventricular function was
      significantly increased at 30 days following CABG surgery. The myocardial
      segments that were normal before CABG had reduced contractile functions at 5
      minutes after CABG but normal segments showed a significant improvement from 5 to
      30 minutes. The function of this region could not reach its initial status. The
      segments that had severe impairments of contractile function before the
      revascularization showed significant improvements at 30 minutes following CABG.
      CONCLUSIONS: In conclusion, a successful coronary revascularization provides an
      improvement in contractility in cases with chronic regional left ventricular
      dysfunction that is not related to irreversible necrosis.

PMID- 15725141
TI  - Coronary artery disease and coronary artery bypass grafting in Behcet's disease.
AB  - There is a high frequency of pseudoaneurysm formation in patients with Behcet's
      disease and their inflammed and fragile tissues are difficult to manipulate. Five
      patients with Behcet's disease were referred to our cardiovascular surgery
      department for coronary artery bypass grafting (CABG). Three of them were
      operated and two were treated medically. Patients that were managed medically had
      left anterior descending (LAD) lesions below 80% and their stable angina pectoris
      responded well to medication. There was no early mortality and morbidity. One
      patient developed pseudoaneurysm of ascending aorta and femoral artery. This
      patient died in the late postoperative period. At follow-up the operated patients
      were in Canadian Cardiovascular Society (CCS) Class I, while the medically
      treated patients were in CCS Class II. Mean follow-up period was 41 +/- 36.21
      months. Coronary artery disease (CAD) is extremely rare detected in patients with
      Behcet's disease. The affected patients are usually young males. Coronary artery
      bypass grafting is also rarely performed in these patients and long-term results
      of such operations are not available in the literature. We present five patients
      with Behcet's disease that had CAD, three operated and two medically treated, and
      report their long-term results. We suggest a conservative approach in patients
      with Behcet's disease because of the high risk of pseudoaneurysm formation in the
      postoperative period. If CABG cannot be avoided we recommend operating the
      patients on the beating heart with minimal aortic manipulation.

PMID- 15725140
TI  - Off-pump coronary artery bypass grafting: long term angiographic results.
AB  - OBJECTIVE: Although short-term results of off-pump coronary artery bypass
      grafting are well documented, late postoperative data are still scarce. This
      report provides an analysis of late postoperative control angiograms. METHODS:
      265 patients (231 males, 34 females; mean age: 54 +/- 10) underwent postoperative
      angiographic control, after an average postoperative period of 4.2 +/- 2.3 years
      (up to 9 years, a total of 1110 years). A total of 385 distal anastomoses on 258
      internal mammary arteries (IMAs) and 127 saphenous vein grafts (SVGs) were
      evaluated. The primary operation was single bypass in 156 cases (62%), double
      bypass in 98 (34%), and triple or more bypass in 11 (4%). RESULTS: Out of 258
      IMAs, 241 were patent (93%), while SVG patency was 65% with 82 patent grafts out
      of 127 (p < 0.0001). The patency in the lateral branches (62%) and right coronary
      system (64%) were similar. The variables associated with graft occlusion were
      hypercholesterolemia (p = 0.02), poor left ventricular performance (p = 0.03),
      reoperation (p = 0.01), target coronary vessel caliber less than 1.5 mm (p <
      0.0001), poor native coronary vessel quality (p = 0.0003) and low-grade stenosis
      (p = 0.02). In the poor left ventricle group, the left ventricular segmental wall
      motion score was improved (p = 0.004). Consequently, 47 patients underwent
      secondary revascularization (35 PTCA and 12 CABG). The leading indication was
      native coronary artery disease progression, frequently in the circumflex system,
      followed by graft failure. The cases with native vessel disease progression were
      referred to PTCA/stenting, while those with LAD graft occlusion were treated
      surgically. CONCLUSIONS: Probably the best candidates for OPCAB are those having
      target vessels of good caliber and quality, and high-grade stenoses.
      Postoperative lipid-lowering therapy seems to be prudential.

PMID- 15725142
TI  - Minimally invasive aortic valve replacement combined with radiofrequency-modified
      maze procedure.
AB  - The treatment of chronic atrial fibrillation undergoing concomitant cardiac
      surgery is gaining greater acceptance. This is the first reported case of a
      minimally invasive aortic valve replacement combined with a radiofrequency
      modified maze procedure.

PMID- 15725143
TI  - Aortic arch reconstruction with pulmonary autograft patch in coarctation and
      interruption of the aorta.
AB  - The surgical management of the aortic arch pathologies is still subject to
      discussion. Primary end-to-end anastomosis has some complications such as
      bronchial compression, tension in the suture lines, and probability of
      recurrence. On the other hand, patch aortoplasties combined with end-to-end
      anastomosis carry the risk of aneurysm formation and recurrence. Considering the
      growth potential, pulmonary autograft patch use in aortic arch reconstructions
      has recently been introduced into clinical practice. In this study, we present
      the early findings of combined end-to-end anastomosis and pulmonary autograft
      patchplasty procedure in six patients. According to our experience the technique
      applied in this report seems to be more advantageous than other conventional
      approaches.

PMID- 15725144
TI  - Inhaled prostacyclin, nitric oxide, and nitroprusside in pulmonary hypertension
      after mitral valve replacement.
AB  - OBJECTIVE: Pulmonary hypertension increases morbidity and mortality in patients
      undergoing heart surgery. Mitral valve stenosis is frequently associated with an
      increase in pulmonary vascular resistance (PVR). Cardiopulmonary bypass
      exacerbates pulmonary hypertension in patients undergoing cardiac surgery. The
      aim of this study was to compare the hemodynamic effects of inhaled prostacyclin
      and nitric oxide and the administration of i.v. nitroprusside during cardiac
      surgery with a clinical, pharmacodynamic dose-response, prospective, randomized,
      and double-blind study (Group A: inhaled prostacyclin; Group B: inhaled nitric
      oxide; Group C: nitroprusside). MATERIALS AND METHODS: Fifty-eight patients with
      mitral valve stenosis and elevated PVR (>200 dynes sec/cm5) after mitral valve
      surgery were studied. Inhaled prostacyclin and nitric oxide were administered at
      concentrations of 10 g/min and 20 ppm, respectively. Nitroprusside i.v. was
      administered at the dose of 5-15 g/min. RESULTS: Prostacyclin and nitric oxide
      produced a significant dose-related decrease of mean pulmonary arterial pressure,
      pulmonary vascular resistance, and transpulmonary gradient. A significant
      increase in cardiac output was observed in both groups. In Group C, nitroprusside
      administration was interrupted in 62% patients due to occurrence of systemic
      hypotension. CONCLUSIONS: Inhaled prostacyclin and nitric oxide are effective in
      the treatment of postoperative pulmonary hypertension in patients with mitral
      valve stenosis undergoing mitral valve surgery. Both drugs improve cardiac output
      and reduce mean pulmonary arterial pressure, pulmonary vascular resistance, and
      trans-pulmonary gradient. They may be useful in patients with acute right
      ventricular failure following cardiac surgery. In comparison to nitric oxide,
      inhaled prostacyclin is free from toxic side effects and is easier to administer.

PMID- 15725145
TI  - Management of an ascending aortic aneurysm with coronary artery disease and
      tracheal compression from a substernal goiter.
AB  - We report the case of a 61-year-old female, who presented with a history of
      chronic fatigue, dyspnea on exertion, a widened mediastinum with tracheal
      deviation on chest X-ray, and a neck mass. After a diagnostic workup, the patient
      was found to have a paratracheal mass extending into the chest in addition to a
      6.5 cm ascending aortic aneurysm with aortic insufficiency, and a 70% stenosis of
      the right coronary artery. She underwent successful resection of a substernal
      goiter via a neck incision facilitated by a previously performed sternotomy for a
      concomitant ascending aortic root replacement and a bypass utilizing the RIMA to
      the distal RCA.

PMID- 15725146
TI  - Transfusion-free cardiac surgery with cardiopulmonary bypass in a 2.2-kg neonate.
AB  - Particularly in neonates, complex cardiac surgery employing cardiopulmonary
      bypass normally requires the transfusion of autologous blood components. This is
      predominately caused by the relatively high priming volume of the circuit with
      subsequent extreme hemodilution. We report on a synoptic approach to avoiding
      transfusions in a 2.2 kg neonate with scheduled for correction of an intracardiac
      total anomalous pulmonary venous connection to the coronary sinus and a
      persistent foramen ovale. In this patient with a preoperative hemoglobin value of
      16.5 g/dL, minimization of the cardiopulmonary bypass circuit, adjustment of the
      perfusion technique and strict reduction of blood sampling resulted in complete
      avoidance of transfusions during the entire course of the operation while
      maintaining safe hemoglobin levels, which never fell below a concentration of 8
      g/mL.

PMID- 15725147
TI  - Successful stenting for congenital coarctation of the distal thoracic aorta
      (middle aortic syndrome) in an adult.
AB  - We report a successful stent implantation for a coarctation lesion of the lower
      thoracic aorta in a 44-year-old male. This patient had suffered from claudication
      of both legs for 30 years. An aortogram revealed a coarctation of the distal
      thoracic aorta at T11 level with 60 mmHg peak systolic pressure gradient of
      across the lesion. A balloon angioplasty followed by an 18 mm x 40 mm sized stent
      implantation was performed successfully. The peak systolic gradient across the
      coarctation decreased from 60 to 15 mmHg. The patient's symptom was relieved
      immediately after stenting. No significant or adverse events were observed during
      7 months clinical follow-up. Follow-up aortogram after 7 months revealed no
      restenosis with an improved pressure gradient. Adults with congenital coarctation
      of the descending thoracic aorta can be successfully treated by stent
      implantation.

PMID- 15725148
TI  - Successful treatment of mucormycosis in the pulmonary artery after cardiac
      surgery.
AB  - Mucormycosis endocarditis after cardiovascular surgery is a rare and usually
      fatal complication. Here, we report one case of mucormycosis occurring in the
      pulmonary artery and the residual patent ductus arteriosus (PDA) in a 9-year-old
      girl, who had been successfully cured with the combination of the emergent
      surgical removal of infected tissues and the subsequent antifungal drug therapy.

PMID- 15725149
TI  - Brucella endocarditis with repeated mitral valve replacement.
AB  - Brucella endocarditis, although a rare complication of brucellosis, is a life
      threatening and often under-diagnosed complication. Despite its high mortality
      rate with combined medical and surgical treatment, has a low occurrence rate in
      cases of brucellosis. Here we describe a patient who underwent mitral valve
      replacement for 3 times due to underdiagnosis of Brucella endocarditis. If a
      valve replacement fails because of an unknown reason, the doubt of a Brucella
      infection should be kept in mind for accurate treatment of such patients.

PMID- 15725150
TI  - A quadricupsid aortic valve.

PMID- 15725151
TI  - A 32-year experience with surgical repair of sinus of valsalva aneurysms.
AB  - INTRODUCTION: Sinus of Valsalva (SoV) aneurysms are rare (0.15% to 1.5% CPB
      cases) and five times more frequent in Asians. Usually congenital, SoV aneurysms
      arise from the right or noncoronary sinus, are associated with other cardiac
      defects, and are repaired primarily or with a patch. Acquired SoV aneuryms
      develop secondary to infection or trauma. Here, we describe our 32-year
      experience with SoV aneurysm repair in a Western population. METHODS: A
      retrospective review identified 22 patients who underwent SoV aneurysm repair
      between 1971 and 2003. Data is presented as mean +/- standard error (median).
      RESULTS: Dyspnea was the most common presenting symptom. Nineteen of 22 patients
      were ruptured at the time of operation; three were found incidentally. Fifteen
      patients had associated cardiac defects including ventricular septal defect (VSD)
      (6), aortic insufficiency (6), and coarctation (3). One patient, repaired
      primarily, required reoperation for recurrence. All other patients underwent
      patch repair. The operative survival was 95% (21/22). There were five known late
      deaths at 6.6 +/- 2.3 (5.7) years post-repair. Five and ten year survival rates
      were 84.9 +/- 11% and 59.4 +/- 17%, respectively. CONCLUSION: Observed
      differences in the sinus of origin, age at presentation, associated cardiac
      malformations, and mortality in our Western series versus previous Asian cohort
      studies likely reflect a racial disparity and higher prevalence of acquired
      versus congenital SoV aneurysms. We recommend a thorough search for a VSD in all
      cases and use of patch repair, regardless of size, to reduce risk of recurrence.

PMID- 15725153
TI  - Ejection fraction velocity ratio as an indicator of aortic stenosis severity.
AB  - BACKGROUND: Despite the widespread use of the continuity equation in the
      estimation of aortic valve area (AVA) in patients with aortic stenosis, it is
      subject to errors, time consuming, and can be technically demanding. As such,
      simpler methods of assessing aortic stenosis severity have been pursued. METHODS:
      The ejection fraction velocity ratio [EFVR = ejection fraction (%) / maximal
      aortic velocity (m/sec)] was compared to AVA determined with the continuity
      equation in 857 patients with aortic stenosis and varying degrees of LV systolic
      dysfunction. Severe aortic stenosis was defined as an AVA < 1.0 cm2. RESULTS:
      There was good to excellent correlation between our index and aortic valve area
      (P < 0.001 for each ejection fraction subgroup). Receiver operating
      characteristic analysis showed that the EFVR functioned well with areas under the
      curve between 0.893 and 0.938. CONCLUSION: The EFVR is a simple noninvasive
      method for screening patients for an AVA of 1.0 cm2. It could be used as a
      screening test or in lieu of the continuity equation particularly when there is
      problematic measurement of either the LVOT diameter or velocity.

PMID- 15725155
TI  - The Doppler-derived myocardial performance index is determined by both left
      ventricular systolic and diastolic function as well as by afterload and left
      ventricular mass.
AB  - OBJECTIVES: To investigate if the newly developed Doppler-derived myocardial
      performance index (MPI, also denoted TEI-index) is associated with variables
      reflecting both left ventricular (LV) systolic and diastolic function, as well as
      variables reflecting preload, afterload, and LV geometry. MATERIAL: An
      echocardiographic examination including Doppler was carried out in 446 men aged
      70 in a population-based survey (the ULSAM-study, Uppsala Longitudinal Study of
      Adult Men). RESULTS: In multiple regression analysis, MPI was independently
      associated with ejection fraction (P < 0.001), E/A ratio (P < 0.001), total
      peripheral resistance index (P < 0.001), stroke volume to pulse pressure ratio (P
      < 0.02), stroke index (P < 0.01), and LV mass (P < 0.04), but not with heart rate
      or blood pressure. CONCLUSION: The echocardiographically determined myocardial
      performance index is determined by both LV systolic and diastolic function as
      well as by afterload and left ventricular mass.

PMID- 15725154
TI  - Impact of body mass index on markers of left ventricular thickness and mass
      calculation: results of a pilot analysis.
AB  - Specific correlations between body mass index (BMI) and left ventricular (LV)
      thickness have been conflicting. Accordingly, we investigated if a particular
      correlation exists between BMI and echocardiographic markers of ventricular
      function. METHODS: A total of 122 patients, referred for routine transthoracic
      echocardiography, were included in this prospective pilot study using a 3:1
      randomization approach. Patient demographics were obtained using a questionnaire.
      RESULTS: Group I consisted of 80 obese (BMI was >30 kg/m2), Group II of 16
      overweight (BMI between 26 and 29 kg/m2), and Group III of 26 normal BMI (BMI <
      25 kg/m2) individuals. No difference was found in left ventricular wall
      thickness, LV end-systolic cavity dimension, fractional shortening (FS), or
      pulmonary artery systolic pressure (PASP) among the groups. However, mean LV end
      diastolic cavity dimension was greater in Group I (5.0 +/- 0.9 cm) than Group II
      (4.6 +/- 0.8 cm) or Group III (4.4 +/- 0.9 cm; P < 0.006). LV mass indexed to
      height(2.7) was also significantly larger in Group I (61 +/- 21) when compared to
      Group III (48 +/- 19; P < 0.001). Finally, left atrial diameter (4.3 +/- 0.7 cm)
      was also larger (3.8 +/- 0.6 and 3.6 +/- 0.7, respectively; P < 0.00001).
      DISCUSSION: We found no correlation between BMI and LV wall thickness, FS, or
      PASP despite the high prevalence of diabetes and hypertension in obese
      individuals. However, obese individuals had an increased LV end-diastolic cavity
      dimension, LV mass/height(2.7), and left atrial diameter. These findings could
      represent early markers in the sequence of cardiac events occurring with obesity.
      A larger prospective study is needed to further define the sequence of cardiac
      abnormalities occurring with increasing BMI.

PMID- 15725156
TI  - Ischemic mitral valve repair: predictive significance of restrictive left
      ventricular diastolic filling.
AB  - AIM: The aim of the present study was to evaluate the impact of left ventricular
      (LV) diastolic filling impairment on postoperative results in patients with low
      LV ejection fraction (EF) undergoing combined coronary artery bypass grafting
      (CABG) and mitral valve (MV) repair. METHODS AND RESULTS: Study population
      consisted of 53 patients with ischemic MV incompetence and LV systolic
      dysfunction (mean EF-26.1 +/- 6%), who underwent CABG with MV repair. Patients
      were divided into three groups according to the LV diastolic filling pattern.
      Study protocol included evaluation of perioperative mortality (30 days inhospital
      mortality), NYHA functional class, and two-dimensional Doppler echocardiographic
      examination preoperatively, 10-14 days, and 12 months after surgery. The highest
      perioperative mortality rate (33.3%), unimproved functional status (in 78.5% of
      the patients, NYHA functional class remained unchanged late after surgery), and
      hemodynamic deterioration (LV dilatation, progression of mitral regurgitation
      (MR) was observed in the restriction group). Though early after surgery, MR
      reduction was significant in this group, at even one year after surgery 85.7% of
      patients presented with >grade 1 of MR (P < 0.05). Logistic regression analysis
      showed that restrictive LV diastolic filling is an important independent
      preoperative marker (P = 0.035) of progression of MR late after MV repair.
      CONCLUSION: In patients with severe LV dysfunction undergoing combined CABG and
      MV repair, restrictive LV diastolic filling pattern is an important preoperative
      marker of high perioperative mortality rate, further negative remodeling of LV,
      and progression of mitral regurgitation late after MV repair.

PMID- 15725157
TI  - Feasibility of measuring coronary flow velocity and reserve in the left anterior
      descending coronary artery by transthoracic Doppler echocardiography in a
      relatively obese American population.
AB  - BACKGROUND: Transthoracic Doppler echocardiography (TTDE) assessment of coronary
      flow velocity reserve (CFVR) has been validated in Asian and European centers.
      This methodology has not gained acceptability in the United States due to the
      bias that coronary flow velocity (CFV) by TTDE might be difficult in an obese
      population with relatively poor acoustic windows. METHODS: Baseline CFV in the
      left anterior descending coronary artery (LAD) by TTDE was obtained in 67
      nonselected American patients. A subset of 38/67 received adenosine infusion for
      measuring CFVR of the LAD. PURPOSE: The aim of this study was twofold: (1) to
      determine the feasibility of measuring CFV and CFVR in the LAD by TTDE in a
      relatively obese American population, and (2) to compare CFV and CFVR values in
      this population with those previously obtained in a group of Japanese patients.
      RESULTS: The mean body mass index (BMI) of the American population (28 +/- 6
      kg/m2, range: 18-46 kg/m2) was significantly higher than that of the Japanese
      group (23 +/- 4 kg/m2, range: 15-37 kg/m2). Twenty-five American patients were
      classified as obese (BMI >30 kg/m2). Baseline CFV was obtained in 60/67 patients
      (feasibility: 90%) with a 10% need for intravenous contrast agent to enhance the
      delineation of the CFV envelope. The success rate in recording CFVR in American
      patients (92%) was nearly identical to that of a Japanese group (99%). The time
      averaged peak diastolic coronary flow velocity increased from 15.6 +/- 5.5 cm/sec
      at baseline to 47.1 +/- 17.9 cm/sec during adenosine infusion, and CFVR was
      calculated to be 3.22 +/- 1.15 (range: 0.94-5.69). Intraobserver and
      interobserver variability for the CFV recording was 4.7 and 6.2%, respectively.
      CONCLUSIONS: These results suggest that the noninvasive measurement of CFV and
      CFVR of the LAD is feasible even in a relatively obese American population.
      Furthermore, the success rates for recording CFV and CFVR are similar to those
      measured in a Japanese population. This methodology has the potential to provide
      useful physiological information on the coronary circulation in American
      patients.

PMID- 15725158
TI  - Ultrasound tissue characterization by integrated backscatter for analyzing
      Fluorouracil induced myocardial damage.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) cardiotoxicity is a well-known clinical
      phenomenon whose pathophysiology remains controversial. Cyclic variation of
      integrated backscatter (CVIBS) assesses acoustic properties of myocardium that
      may reflect both contractility and structural changes. The aim of this study was
      to evaluate CVIBS alterations in cancer patients under high-dose leucovorin and
      infusional 5-FU (HDLV5FU) chemotherapy. METHOD: We prospectively evaluated 37
      cancer patients under HDLV5FU treatment. Transthoracic echocardiography and CVIBS
      were performed at the 0th, 48th hours, and on day 15 of the first cycle. The
      parasternal long-axis view was preferred to obtain the image of integrated
      backscatter and mainly two regions of interest--interventricular septum (IVS) and
      posterior wall (PW)--were used. RESULTS: Clinical cardiotoxicity was observed in
      two patients. No significant differences were detected in pre- and posttreatment
      conventional echocardiography evaluations. However, both the IVS (9.3 +/- 1.0 to
      8.1 +/- 1.2 dB, P < 0.001) and PW (9.1 +/- 0.7 to 7.8 +/- 0.9 dB, P < 0.001)
      CVIBS values significantly decreased in all patients. All values were returned to
      pretreatment levels (9.2 +/- 0.9 dB in the CVIBS-IVS and 8.9 +/- 0.6 dB in CVIBS
      PW, respectively) on day 15 after the treatments. CONCLUSION: This study suggests
      that HDLV5FU may cause acute transient alterations in CVIBS values in the absence
      of clinical symptoms and signs of cardiotoxicity. The clinical value of CVIBS
      should be further studied in patients receiving 5-FU-based therapy.

PMID- 15725159
TI  - Lack of prognostic value of normalized integrated backscatter analysis of
      myocardium in patients with thalassemia major: a long-term follow-up study.
AB  - BACKGROUND: Patients with beta-thalassemia major often present with severe anemia
      and must undergo continuous transfusion therapy, consequently developing iron
      overload leading to hemochromatosis. Because of these the iron deposits and/or
      secondary structural changes, patients develop an increase in myocardial
      integrated backscatter (IB). AIM: To investigate the prognostic value of
      analyzing acoustic quantitative properties of the myocardium in patients with
      beta-thalassemia major. PATIENTS AND METHODS: Between 1989 and 1990, 38 patients
      (mean age: 18 years, range: 7-26, 21 males) with beta-thalassemia major and
      without clinical signs of cardiac failure were enrolled prospectively. All
      patients were on chelation therapy (desferroxiamine). To obtain quantitative
      operator-independent measurement of the IB signal of the left ventricular septum
      and posterior wall, the ultrasonic radiofrequency signal integrated values were
      normalized to the pericardial interface and expressed in percentage (IB%).
      RESULTS: Follow-up was 122 +/- 36 months, during which 15 events (7 cardiac
      deaths and 8 heart failures) occurred. The event-free survival was comparable in
      patients with normal and abnormal IB%. Septal IB% was 33 +/- 14 in the 15
      patients with events, and 33 +/- 12 in the 25 patients without events (P = ns).
      The %IB had no prognostic value in this population. A prognostic value was found
      in multivariate analysis for patient refusal/noncompliance of chelation therapy
      (P = 0.02, OR: 4.37, 95% CI: 1.72-16.9) and also body mass index (P = 0.04, OR:
      1.2, 95% CI: 1.0-1.4). CONCLUSION: Analysis of end-diastolic IB% of myocardium in
      patients with beta-thalassemia and iron overload was not predictive of adverse
      cardiac events during long-term follow-up in this study.

PMID- 15725160
TI  - Evaluation of left ventricular function in cardiomyopathic mice by tissue Doppler
      and color M-mode Doppler echocardiography.
AB  - Tissue Doppler imaging (TDI) and color M-mode Doppler flow propagation velocity
      (Vp) are used to assess cardiac function in humans, but the feasibility and
      applicability of these measurements to murine cardiomyopathic models of heart
      failure remain unclear. Left ventricular (LV) function was measured by TDI and Vp
      among mice exhibiting severe dilated cardiomyopathy (TOT), pressure-overload
      hypertrophy (TAC), and normal controls (NTG). Transmitral flow pattern in TACs
      and TOTs showed a restrictive filling pattern, but early diastolic mitral annulus
      velocity was comparable among the three studied groups. Propagation velocity in
      an anesthetized state was comparable in all three groups. However, while Vp
      increased in all three groups in the conscious state, the increase in NTGs was
      statistically greater than in TACs and TOTs. Collectively, results indicate that
      color M-mode Doppler echocardiography can be used to assess LV function in mice.
      Furthermore, Vp is depressed by anesthesia, a complication that can lead to
      misinterpretation of LV function in normal hearts.

PMID- 15725161
TI  - Valve morphology in antiphospholipid antibody syndrome: echocardiographic
      features.
AB  - Primary antiphospholipid antibody (PAP) syndrome can present with a variety of
      clinical manifestations including cardiac valvular lesions. Prior reports of the
      valvular lesions associated with PAP have been nonspecific. The purpose of this
      paper is to present four cases of patients with documented PAP and demonstrate
      the characteristic transesophageal echocardiographic features. The primary
      feature is focal, symmetrical, nodular thickening at the leaflet's coaptation
      points.

PMID- 15725162
TI  - A giant dissecting aneurysm of ascending aorta.
AB  - Aortic aneurysm is a serious clinical challenge for the cardiologist. Aneurysm
      expansion frequently associated with significant dissection and rupture risk.
      Currently available diagnostic modalities make earlier diagnosis and therapy
      possible hence giant aneurysm with dissection is relatively rare. In this case
      report, we present a patient with giant aortic aneurysm with dissection.

PMID- 15725163
TI  - Saphenous vein graft aneurysm masquerading as a right atrial mass.
AB  - We report a case of a large saphenous vein graft (SVG) aneurysm masquerading as a
      right atrial mass on transesophageal echocardiogram. Cardiac magnetic resonance
      angiography reliably made a diagnosis of SVG aneurysm extrinsically compressing
      right atrium. This case illustrates the importance of using combined imaging
      modalities for the diagnosis and management of cardiac masses.

PMID- 15725164
TI  - Elevated brain natriuretic peptide and troponin I in a woman with generalized
      weakness and chest pain.
AB  - We report the case of a female patient emergently transferred to our institution
      with the presumptive diagnosis of myocardial infarction in heart failure given
      the constellation of symptoms and abnormal laboratory cardiac markers on
      presentation. However, on closer examination, prior to instituting an invasive
      cardiac work-up, pulmonary embolism was instead strongly considered to explain a
      common etiology. Therefore, an echocardiogram was promptly obtained, which
      revealed the presence of McConnell's sign. This noninvasive imaging modality
      proved to be critical in the prompt recognition and management of this patient.
      We reviewed the literature regarding the use of echocardiography and the clinical
      significance of abnormal cardiac markers in patients presenting pulmonary
      embolism.

PMID- 15725165
TI  - Live three-dimensional transthoracic echocardiographic demonstration of septal
      perforator coronary artery-left ventricle fistulas following myectomy.
AB  - We present an adult patient with hypertrophic cardiomyopathy status post septal
      myectomy in whom live three-dimensional transthoracic echocardiography (3D TTE)
      demonstrated two septal perforator coronary arteries opening directly into the
      left-ventricular outflow tract. Only one of these fistulas could be demonstrated
      by two-dimensional transthoracic echocardiography (2D TTE). Our case demonstrates
      the potential usefulness of 3D TTE as a supplement to 2D TTE in the assessment of
      septal coronary artery-left ventricle fistulas.

PMID- 15725166
TI  - Transesophageal echocardiographic visualization of a rupturing thoracic aortic
      aneurysm in progress.

PMID- 15725167
TI  - Transesophageal echocardiographic detection of aortic dissection with reentry
      site at the level of the celiac artery.

PMID- 15725168
TI  - Editorial: TEE of the descending aorta: anatomic coherence provided by the celiac
      artery.

PMID- 15725169
TI  - Papillary fibroelastoma and Lambl's excrescences: echocardiographic diagnosis and
      differential diagnosis.

PMID- 15725170
TI  - Improving the oral health of older people: the approach of the WHO Global Oral
      Health Programme.
AB  - The proportion of older people continues to grow worldwide, especially in
      developing countries. Non-communicable diseases are fast becoming the leading
      causes of disability and mortality, and in coming decades health and social
      policy-makers will face tremendous challenges posed by the rapidly changing
      burden of chronic diseases in old age. Chronic disease and most oral diseases
      share common risk factors. Globally, poor oral health amongst older people has
      been particularly evident in high levels of tooth loss, dental caries experience,
      and the prevalence rates of periodontal disease, xerostomia and oral
      precancer/cancer. The negative impact of poor oral conditions on the quality of
      life of older adults is an important public health issue, which must be addressed
      by policy-makers. The means for strengthening oral health programme
      implementation are available; the major challenge is therefore to translate
      knowledge into action programmes for the oral health of older people. The World
      Health Organization recommends that countries adopt certain strategies for
      improving the oral health of the elderly. National health authorities should
      develop policies and measurable goals and targets for oral health. National
      public health programmes should incorporate oral health promotion and disease
      prevention based on the common risk factors approach. Control of oral disease and
      illness in older adults should be strengthened through organization of affordable
      oral health services, which meet their needs. The needs for care are highest
      among disadvantaged, vulnerable groups in both developed and developing
      countries. In developing countries the challenges to provision of primary oral
      health care are particularly high because of a shortage of dental manpower. In
      developed countries reorientation of oral health services towards prevention
      should consider oral care needs of older people. Education and continuous
      training must ensure that oral health care providers have skills in and a
      profound understanding of the biomedical and psychosocial aspects of care for
      older people. Research for better oral health should not just focus on the
      biomedical and clinical aspects of oral health care; public health research needs
      to be strengthened particularly in developing countries. Operational research and
      efforts to translate science into practice are to be encouraged. WHO supports
      national capacity building in the oral health of older people through
      intercountry and interregional exchange of experiences.

PMID- 15725171
TI  - The life course approach: explaining the association between height and dental
      caries in Brazilian adolescents.
AB  - AIM: To investigate the relationship between height and dental caries in
      Brazilian adolescents. METHODS: A cross-sectional survey design was used to
      collect retrospective data. Of 764 eligible 13-year-old adolescents enrolled in
      urban private or public schools in a Brazilian town, 652 were clinically examined
      and interviewed. Data were collected on socioeconomic circumstances, family
      related variables, oral health behaviour and anthropometric measures (height and
      weight). Dental caries was measured by decayed, missing and filled teeth (DMFT)
      index. The DMFT was categorized according to two levels of severity (low DMFT </=
      6; high DMFT > 6) using the 75th percentile of the distribution as the cut-off
      point. Data analysis involved multiple logistic regression. RESULTS: Adolescents
      who were the second or later child were 1.90 times more likely to have a high
      DMFT, whilst being a taller adolescent had a protective effect on caries
      experience (OR = 0.04; 95% CI = 0.00-0.79). In addition, adolescents from rural
      areas (OR = 2.74; 95% CI = 1.56-4.82), those whose mothers had less than 8 years
      of education (OR = 2.10; 95% CI = 1.03-4.27) and those who reported high levels
      of paternal punishment (OR = 1.60; 95% CI = 1.02-2.52) had an increased risk of
      having a high DMFT. CONCLUSION: There is a relationship between height and dental
      caries experience in this sample of Brazilian adolescents.

PMID- 15725173
TI  - Validation of a Chinese version of the dental anxiety inventory.
AB  - OBJECTIVES: To translate the English version of Dental Anxiety Inventory (DAxI)
      and its short-form (SDAxI) and to validate their use in Hong Kong Chinese.
      METHODS: The DAxI and SDAxI were translated into Chinese. A total of 500 adults
      (18-64 years) were interviewed, the Chinese DAxI, Symptom Checklist 90 (SCL-90),
      Depression Anxiety Stress Scales (DASS) and State-Trait Anxiety Inventory (STAI)
      were completed. Based on their initial DAxI scores, 135 interviewees were invited
      to attend a dental examination 1 month later. Then, the subjects completed the
      DAxI again, together with Beck Anxiety Inventory (BAI) which measured the state
      anxiety level of the participants. Two months after the initial interview, all
      500 subjects were asked to complete the DAxI again. Another 300 adults were
      recruited and interviewed for the SDAxI validation. RESULTS: Cronbach's alpha of
      the Chinese DAxI and SDAxI were 0.77 and 0.80 and the test-retest correlation
      coefficients were 0.90 and 0.84, respectively. High correlation between BAI and
      DAxI scores and its stability over time supported construct validity of the
      Chinese DAxI. Small positive correlations between the DAxI and other subscales of
      the SCL-90, DASS and STAI supported discriminant validity of the instrument. The
      SDAxI demonstrated comparable validity and reliability with DAxI. CONCLUSION: The
      translated Chinese DAxI demonstrated good validity and reliability. It is
      available for use in dental anxiety research in adult Chinese. In situations
      where a short-form is desirable, the Chinese SDAxI is a simple, valid, reliable
      and interpretable scale for measuring dental anxiety in both research and dental
      practice.

PMID- 15725172
TI  - Oral white patches in a national sample of medical HIV patients in the era of
      HAART.
AB  - OBJECTIVES: Several types of HIV-related oral mucosal conditions have been
      reported to occur during the course of HIV disease progression. Of these, few may
      be manifested as 'white' lesions and many are noticeable to the patient. This
      paper examines the relationships between social, behavioral and medical aspects
      of HIV infection and reporting an occurrence of oral white patches (OWP) by HIV
      infected patients. METHODS: The subjects are participants in all three interviews
      in the HIV Cost and Services Utilization Study (HCSUS). The subjects were
      selected using a three-stage probability sampling design. The multivariate
      analysis is based on 2109 subjects with nonmissing binary outcome variable for
      all three waves representing a national sample of 214 000 individuals. The
      multivariate model was fitted using generalized estimating equations (GEE) by
      implementing the XTGEE command in STATA. RESULTS: We estimate that 75 000 persons
      (35%) reported at least one incident of OWP, of these 14 000 reported having OWP
      during all three interviews, and that the rate of reporting declined over the
      three HCSUS waves. The multivariate analysis showed seven variables that were
      significant predictors of at least one report of OWP. CONCLUSIONS: Compared with
      persons on HAART therapy, patients on other regimens or taking no antiviral
      medications were 23-46% more likely to report an incident of OWP. Compared with
      whites, African Americans were 32% less likely to report OWP, while current
      smokers were 62% more likely than nonsmokers. Being diagnosed with AIDS and
      having CD4 counts less than 500 significantly increased the likelihood of
      reporting OWP.

PMID- 15725174
TI  - Effectiveness of health care worker training on the oral health of elderly
      residents of nursing homes.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of a staff training
      programme on mouth care on the oral health of elderly residents of long-term care
      institutions. METHODS: Seventy-eight residents of five long-stay institutions
      were enrolled and underwent a baseline oral health assessment. Staff caring for
      residents in three of the sites received intensive training in mouth care. This
      comprised lecture and video material complemented by clinical demonstrations. The
      oral health of residents at all five sites was reassessed at periods of 3 and 9
      months. Staff caring for residents in the remaining two institutions were then
      provided with mouth care training and all patients were reassessed at 18 months.
      Statistical analyses were undertaken to examine for significant changes in
      selected oral health parameters after training, within each group. RESULTS: Oral
      mucosal disease and oral dryness were common at baseline. The staff training was
      well received. Following staff training, there was a significant reduction in the
      number of residents left to undertake their own oral care. There were significant
      improvements in denture hygiene and a reduction in the number of residents
      wearing dentures overnight. The prevalence of oral mucosal disease dropped, with
      significant reductions in angular cheilitis and denture stomatitis. CONCLUSION:
      This education programme was effective in changing oral health care procedures
      within long-stay institutions for the elderly, with measurable improvements in
      oral health of the residents.

PMID- 15725175
TI  - Cross-cultural validation of a short form of the Oral Health Impact Profile for
      temporomandibular disorders.
AB  - OBJECTIVES: We set out to develop and validate an Italian version of the Oral
      Health Impact Profile Questionnaire (OHIP) that is appropriate for use in
      temporomandibular disorders (TMD). METHODS: At first, we had the questionnaire
      translated from English into Italian by three bilingual individuals whose mother
      tongue was Italian and thus had three different versions of the questionnaire.
      These were translated back into English by a native English speaker and the
      version closest to the original English OHIP was selected. The validation of a
      questionnaire generally involves the study of the psychometric properties of the
      instrument: its validity and reliability. Before studying these properties, we
      assessed the factorial structure of the questionnaire. RESULTS: The number of
      eigenvalues >1, computed by exploratory factor analysis, was seven. The
      percentage of cumulative variability explained by a model with six dimensions is
      66, whereas that explained by a model with seven dimensions is 70. Therefore,
      considering that the increment of explained variability due to the seventh
      dimension is low (3.68%) and that the seventh eigenvalue is very close to 1, we
      considered a six-factor model capable of explaining the factorial structure of
      the data. Content analysis suggested eliminating the item 'Felt Self-conscious',
      as most of the subjects did not understand its meaning. Spearman correlation
      coefficients showed an association between the scores of all the different
      subscales and the variable for pain. All the coefficients were significantly
      different from 0 (P < 0.05). Cronbach's alpha value, always >0.70, showed quite a
      good reliability for each of the six subscales. CONCLUSIONS: These results reveal
      a reasonable degree of cross-cultural consistency between the two versions of the
      OHIP, and thus indicate that our Italian version is valid.

PMID- 15725176
TI  - Dentist-assistant communication style: perceived gender differences in The
      Netherlands and Northern Ireland.
AB  - OBJECTIVES: To assess communication style differences with the (female) dental
      assistant, as perceived by male and female dentists. METHODS: Data were collected
      from 216 Dutch (male: 99; female: 117) and 261 Northern Irish (male: 135; female:
      126) dentists (overall response rate: 60%). Respondents filled in a self-report
      questionnaire (one follow-up mailing), with 22 items on staff communication
      style. Using principal component analysis, four distinguishable factors could be
      extracted: businesslike leadership style (seven items, Cronbach's alpha = 0.87),
      friendly leadership style (seven items, alpha = 0.87), professional interacting
      style (four items, alpha = 0.83) and gender interacting style (four items, alpha
      = 0.83). RESULTS: manova indicated a main effect for gender [F(8,946) = 10.905, P
      < 0.001] and for country [F(4,474) =4.197, P = 0.002] on the communication style
      scales. Male dentists, compared with female colleagues, showed higher mean scores
      on businesslike leadership style and gender interacting style, whereas female
      dentists showed higher mean scores on friendly leadership style and professional
      interacting style. Dutch dentists showed higher mean scores on friendly
      leadership style and professional interacting style than their Northern Irish
      colleagues. No interaction effect between gender and country was found. Dentist's
      age and length of assistant's employment (in years) partly explained differences
      in means. CONCLUSION: Male and female dentists perceive their communication with
      the assistant differently; male dentists tend to be influenced by the gender
      differences, female dentists by striving for friendliness. Some country
      differences were found. Increasing influx of young female dentists underlines the
      relevance of this topic in dental education and for future research.

PMID- 15725177
TI  - Development and validation of the Manchester orofacial pain disability scale.
AB  - OBJECTIVE: To design and validate a self-administered instrument for assessing
      orofacial pain related disability in the general population. METHODS: The 32-item
      questionnaire was developed by open-ended interviews with patients attending
      dental hospital clinics and was subsequently tested on 171 community subjects
      with self-reported orofacial pain and 48 dental hospital patients. RESULTS:
      Construct validity of the instrument was demonstrated in three ways. First,
      levels of reported disability were greater in dental hospital patients than for
      community subjects reporting orofacial pain. Secondly, the instrument was able to
      detect differences in disability levels reported by community subjects who did
      and did not consult with a healthcare professional and those who had acute and
      chronic pain. Thirdly, amongst community subjects with pain, disability scores
      increased with higher pain intensity, pain duration and were greater amongst
      subjects who had sought a consultation. Results of factor analysis identified two
      constructs: physical and psychosocial disabilities, associated with orofacial
      pain. The Cronbach's alpha score was 0.78 and 0.92 for the physical and
      psychosocial constructs, respectively, and this along with item correlation
      values between 0.43 and 0.80 confirmed the internal consistency. CONCLUSION: We
      have therefore designed a valid instrument for assessing the impact of painful
      orofacial conditions in both community and clinic settings.

PMID- 15725178
TI  - Factors related to satisfaction with dental care among 23-year olds in Norway.
AB  - OBJECTIVES: The aims of the present study were to explore (i) the prevalence and
      distribution of satisfaction with dental care among 23-year olds in Norway; and
      (ii) possible factors associated with the same variable. METHODS: A random sample
      of adolescents (n=968) surveyed at age 18 were resurveyed by post at the age of
      23. The questionnaire included the psychometric instruments Dental Satisfaction
      Questionnaire (DSQ), Dental Fear Survey (DFS), Dental Beliefs Survey (DBS), and
      the (WHO) Five Scale Psychological General Well-Being Schedule. RESULTS: The
      response rate was 69%. Of this group, 15% of the subjects were very satisfied,
      and another 15% were very dissatisfied with dental care. The following variables
      explained 58% of the variance of satisfaction with dental care at age 23:
      positive beliefs of the dentist (DBS), low dental anxiety, perception of having a
      dentist to go to, last treatment session not painful/unpleasant, and gender
      (male). Being very satisfied with dental care was associated with high DMFT at
      age 16 and few previous experiences of pain. Being very dissatisfied at age 23
      was associated with low general well-being, previous experiences of pain and
      dislike of the dentist (both reported at age 18). Last dental treatment session
      was reported as very painful or unpleasant by 6.7% of the group. CONCLUSIONS:
      Beliefs of the dentist and pain control seems to be important aspects in young
      adults' evaluation of dental care.

PMID- 15725181
TI  - GA2LEN--The Global Allergy and Asthma European Network.

PMID- 15725180
TI  - Airway remodelling in asthma: models and supermodels?

PMID- 15725182
TI  - Indoor allergens in settled school dust: a review of findings and significant
      factors.
AB  - The school environment can be an important site of exposure to cat, dog, dust
      mite, and cockroach allergens, which have been detected in the settled dust of
      many schools. The sizable body of research that has been published in recent
      years warrants careful examination. This review article informs clinicians,
      researchers, and other parties about the potential for exposure in the school
      environment, factors that affect allergen concentrations, and areas of future
      research. While average concentrations in schools were usually under risk levels
      for symptoms or sensitization, many studies reported at least one location where
      the concentrations exceeded these levels. Maintenance, mechanical, and
      administrative factors were related to allergen levels in schools. From a
      clinical perspective, the school environment in industrialized nations has a
      lower potential for exposure than the home environment, but schools are
      significant for allergic individuals whose home environment has been addressed to
      the extent feasible. From a public health perspective, the school environment
      should be considered as a target for primary and secondary prevention. It can be
      more practical and amenable to intervene on a single school than the hundreds of
      homes in a community. Future research should continue to evaluate which
      interventions are most practical and result in the greatest measurable
      improvements. In addition, research should further examine the relationship
      between allergen exposure in schools and health effects, in order to develop an
      accurate exposure assessment model and risk levels that are specific to the
      school environment.

PMID- 15725183
TI  - Mechanisms of respiratory virus-induced asthma exacerbations.

PMID- 15725184
TI  - Airway remodelling and inflammation in sheep lungs after chronic airway challenge
      with house dust mite.
AB  - BACKGROUND: Remodelling of airway walls is a significant morbidity factor in
      patients suffering from chronic asthma. The relationship between airway
      remodelling and the inflammatory response is not well defined. Sheep have been
      used extensively to model airway disease in humans and represent a suitable model
      to examine airway remodelling. OBJECTIVE: The aim of the present study was to
      develop a model for airway remodelling in sheep after repeated challenge with a
      relevant human allergen to assess the relationship of airway remodelling with
      inflammation. METHODS: Repeated challenges of house dust mite (HDM) extract or
      saline (control) were administered to local lung segments of sheep for a period
      of 6 months. After the last challenge, lung tissues from both challenged and
      unchallenged lung compartments of the same sheep were compared using morphometric
      image analysis and (immuno) histological studies. RESULTS: All HDM-challenged
      sheep developed significant bronchoalveolar lavage eosinophilia during challenge.
      At the end of the challenge period, significant increases in airway collagen and
      airway smooth muscle content were found in a proportion (3/7) of the HDM
      challenged sheep. Hyperplasia of goblet cells and epithelial cells were observed
      in small bronchi and bronchioles exposed to allergen. Irrespective of airway
      remodelling changes, all HDM-challenged, but no saline-challenged sheep,
      displayed significant increases in mast cells in alveolar septa and airway walls
      of challenged lungs compared with untreated lung compartments of the same sheep.
      Significant increases were also observed in CD5 and gamma delta T cell
      subpopulations in all allergen-exposed lung parenchyma. CONCLUSION: A proportion
      of atopic sheep develop typical airway remodelling changes after chronic allergen
      challenge, which is not directly related to the level of allergic inflammation.

PMID- 15725185
TI  - Atopic sensitization and atopic dermatitis in Estonian and Swedish infants.
AB  - BACKGROUND: Early life events seem to have a major impact on the development of
      tolerance or sensitization. OBJECTIVE: The aim of the study was to compare the
      prevalence of sensitization and atopic dermatitis (AD) during the first 2 years
      of life in Estonia and in Sweden. METHODS: Two groups comprising 110 Estonian and
      123 Swedish infants were followed from birth up to 2 years of age. Data about
      symptoms of allergy, infections and use of antibiotics were obtained by
      questionnaires. Clinical examinations, skin prick tests (SPTs) with food and
      inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6,
      12 and 24 months. RESULTS: The cumulative incidence of AD and positive SPTs were
      lower in the Estonian than the Swedish infants (14% vs. 24%; P = 0.06 and 13% vs.
      24%; P = 0.03), while circulating IgE antibodies were more common (39% vs. 27%; P
      = 0.06) and often present without any clinical significance in Estonian children.
      Estonian infants had respiratory illnesses more often and they had received
      antibiotics more frequently. Use of antibiotics increased the risk for positive
      SPT in the Estonian (odds ratio = 1.7, 95% confidence interval = 1.1-2.5), but
      not in the Swedish infants. This may be explained by the use of broad-spectrum
      antibiotics in Estonia, while in Sweden mostly penicillin was prescribed.
      CONCLUSIONS: The prevalence of AD and positive SPTs was lower in the Estonian
      than the Swedish infants, while circulating IgE antibodies were more common and
      often present without any clinical significance. These differences cannot simply
      be explained by infections, or use of broad-spectrum antibiotics in the two
      countries, although more the natural lifestyle in Estonia may be contributing
      factor.

PMID- 15725186
TI  - Allergen-specific sensitization in asthma and allergic diseases in children: the
      study on farmers' and non-farmers' children.
AB  - BACKGROUND: Farmers' children are less frequently sensitized to common allergens
      than the non-farmers' children, but less is known about their sensitization to
      other allergens and its association with clinical diseases. OBJECTIVE: To examine
      the association of farm environment with atopic sensitization, allergic diseases,
      expression of allergen-induced symptoms, and the importance of specific
      sensitization against 'common' (timothy, dog, cat, birch, Dermatophagoides
      pteronyssimus, mugwort) and 'other' (cockroach, horse, Lepidoglyphus destructor,
      cow) allergens for asthma and allergic diseases in children. METHODS: A cross
      sectional study including 344 farmers' and 366 non-farmers' children aged 6-13
      years in eastern Finland, using a self-administered written questionnaire and
      skin prick tests against the above-mentioned allergens. RESULTS: Farmers'
      children had less asthma and allergic diseases and were less often sensitized
      against common allergens than the non-farmers' children. However, little
      difference was observed in sensitization against the other allergens between the
      farmers' (17.2%) and non-farmers (14.5%) children [adjusted odds ratios (aOR)
      1.11 (0.71-1.72)]. Being sensitized against only other allergens, without
      sensitization against common allergens, was unrelated to asthma or allergic
      diseases. Among the single allergens, sensitization against pets or pollen, or
      against horse or cow, had the strongest association with asthma, hayfever, and
      atopic eczema; no such association was seen in D. pteronyssimus, mugwort,
      cockroach, or L. destructor. Farmers' children had significantly less often
      symptoms of allergic rhinitis in contact with dog (aOR 0.32%, 95% confidence
      interval (CI) 0.15-0.67), cat (aOR 0.45, 0.22-0.88), or pollen (aOR 0.58%, 95% CI
      0.37-0.90) than the non-farmers' children. CONCLUSION: Farm environment reduces
      the occurrence of asthma, allergic diseases, and atopic sensitization in
      children, and also the occurrence of allergen-induced rhinitis. Remarkable
      differences were observed between single allergens in their association with
      allergic disease, stressing the importance of allergen selection when defining
      atopy in epidemiological studies.

PMID- 15725187
TI  - Prevalence and main characteristics of schoolchildren diagnosed with food
      allergies in France.
AB  - BACKGROUND: A cross-sectional, descriptive, questionnaire-based survey was
      conducted in Toulouse schools to determine the prevalence of food allergies among
      schoolchildren. OBJECTIVES: The first goal of the survey was to estimate the
      prevalence of food allergies. The second goal was to determine the main
      characteristics of the allergies. METHODS: The questionnaires (3500) were
      distributed in 150 classes in eight schools. The return rate was 77.6% (2716).
      RESULTS: Of the 192 (7.0%) questionnaires with a 'Yes' response (report of a food
      allergy), 182 were retained as reporting true food allergies (6.7%). The
      cumulative and point prevalences were 6.7% [95% confidence interval (CI) 5.8-7.6]
      and 4.7% [95% CI 3.9-5.5], respectively. The point prevalences were 4.0% for the
      children aged 2-5 years, 6.8% for the children aged 6-10 years, and 3.4% for the
      children aged 11-14 years. The main foods reported as causing adverse reactions
      were cow milk (n = 29, 11.9%), eggs (n = 23, 9.4%), kiwis (n = 22, 9.0%), peanuts
      (n = 20, 8.2%), fish (n = 19, 7.8%), tree nuts (n = 19, 7.8%), and shrimp (n =
      13, 5.3%). The average age at which the allergies were detected was 3.4+/-2.8
      years (with a range of 0.1-12 years). The clinical signs of the food allergies
      were cutaneous (n=153, 62.7%), digestive (n = 74, 30.3%), respiratory (n = 17,
      6.9%), and anaphylactic shock (n = 12, 4.9%). CONCLUSION: While well aware of the
      biases inherent in this type of study, we estimated the cumulative and point
      prevalences of food allergies in a population of school-age children in Toulouse
      at 6.7% and 4.7%, respectively. Cow milk, eggs, and peanuts were the main foods
      reported as causing allergies. Exotic fruits, shellfish, and tree nuts appeared
      to be relatively new allergens.

PMID- 15725188
TI  - Effect of cooked and raw egg consumption on ovalbumin content of human milk: a
      randomized, double-blind, cross-over trial.
AB  - BACKGROUND: Maternal avoidance of egg intake has been recommended to treat egg
      allergy in breastfed infants. OBJECTIVE: To determine if the concentration of
      ovalbumin (OVA) in human milk is directly related to the quantity and form of egg
      consumed by breastfeeding mothers. METHODS: Randomized, blinded, cross-over,
      intervention trial. Breastfeeding women (n = 41) attended four clinic days
      between 11 and 14 weeks of lactation and on each day were randomly allocated to
      receive a test breakfast, identical except for the egg content (no egg, one raw
      egg, half a cooked egg or one cooked egg). Breast milk samples were collected at
      two hourly intervals for 8 h and their OVA concentration measured by ELISA.
      RESULTS: There was a direct, dose-response between the amount of cooked egg
      ingested and the peak OVA concentration (no egg 0.05 ng/mL [95% confidence
      interval (CI), 0.01-0.11], half a cooked egg 2.24 ng/mL [95% CI, 0.57-3.91], one
      cooked egg 3.16 ng/mL [95% CI, 1.41-4.91], n = 41, P<0.05) as well as the total
      OVA excretion (no egg 0.18 ng/mL/h [95% CI, 0.04-0.39], half a cooked egg 4.93
      ng/mL/h [95% CI, 1.40-8.46], one cooked egg 9.14 ng/mL/h [95% CI, 4.25-14.03], n
      = 41, P<0.05). The peak concentration and total OVA excretion in response to one
      raw egg did not differ from ingesting half a cooked egg. There was no detectable
      OVA in the breast milk of 24% (10/41) women up to 8 h after any egg challenge.
      CONCLUSION: OVA was detected in the breast milk of lactating women up to 8 h
      after a controlled intake of egg. A dose-response correlation was indicated. As
      excretion of OVA in human milk appears to be a normal phenomenon, further studies
      need to determine the threshold of OVA excretion that leads to symptoms in egg
      allergic breastfed infants.

PMID- 15725189
TI  - Natural history of Hymenoptera venom allergy in Eastern Spain.
AB  - INTRODUCTION: The natural history of stings, the clinical reaction of the patient
      and in vivo and in vitro tests are necessary parameters to assess before
      initiating Hymenoptera venom immunotherapy. In the decision to initiate
      immunotherapy with Hymenoptera venom, it is not usual to evaluate the natural
      history of the disease, which seems to be self-limiting and therefore of variable
      clinical significance. OBJECTIVES: Our aim was to determine the natural history
      of Hymenoptera hypersensitivity over 4 consecutive years in a rural Mediterranean
      population. METHODS: An epidemiological study of Hymenoptera sting reactions and
      possible sensitivity was carried out in 145 randomly selected subjects out of a
      rural Mediterranean population of 600. Seventy-two subjects, including those with
      a history of anaphylaxis, completed the 4-year study. The nature of their
      clinical reactions, age, sex, history of atopy, profession, family history of
      reactions to Hymenoptera insects, time elapsed since the last sting, number of
      stings and specific IgE and IgG were determined (the latter, to the three most
      important insects in the area: Apis mellifera, Polistes dominulus, and Vespula
      germanica). RESULTS: Of the 72 subjects, four subjects had systemic reactions
      (SR), 23 had large local reaction (LLR) and all the others (117) was minor local
      reactions. None who had experienced an SR had a repeat SR when re-stung over the
      4-year study. Of those with LLR, 12 subjects had the same type of reaction and 11
      experienced more mild local reactions when re-stung. In the SR and local reaction
      groups, IgE to honey bee (Hb) increased significantly during the study period,
      whereas in those with only LLR, specific IgE to wasp (Polistes) decreased.
      Specific IgG to Polistes and Vespula (wasps) decreased significantly, whereas
      there was no change in the specific IgG to Hb in any of the groups. The number of
      stings per year decreased at the end of the study in all groups, but positive
      specific IgG was higher in subjects with the greatest number of stings. On
      multivariate analysis using logistic regression, the existence of specific IgE to
      bee venom, male sex, being an agricultural worker, age of over 16 years and more
      than five stings per year are seen as individual or co-factors for developing SR
      or LLR. CONCLUSIONS: The prevalence of SR was 2.8% in our Mediterranean
      population. The evolution of IgE and IgG throughout the 4-year study differed
      depending on the Hymenoptera studied. Adult male agricultural workers are at
      greater risk of having SR or LLR, especially when they have specific IgE to Hb
      and suffer from more than five stings every 4 years.

PMID- 15725190
TI  - Poor association between allergen-specific serum immunoglobulin E levels, skin
      sensitivity and basophil degranulation: a study with recombinant birch pollen
      allergen Bet v 1 and an immunoglobulin E detection system measuring
      immunoglobulin E capable of binding to Fc epsilon RI.
AB  - BACKGROUND: Results from several studies indicate that the magnitude of immediate
      symptoms of type I allergy caused by allergen-induced cross-linking of high
      affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not
      always associated with allergen-specific IgE levels. OBJECTIVE: To investigate
      the association of results from intradermal skin testing, basophil histamine
      release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a
      clinical study performed in birch pollen-allergic patients (n = 18). METHODS:
      rBet v 1-specific IgEs were measured by quantitative CAP measurements and by
      using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of
      binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels
      were measured by ELISA, and basophil histamine release was determined in whole
      blood samples. Intradermal skin testing was performed with the end-point
      titration method. RESULTS: Our study demonstrates on the molecular level that the
      concentrations of allergen-specific IgE antibodies capable of binding to Fc
      epsilon RI and biological sensitivities are not necessarily associated. A
      moderate association was found between cutaneous and basophil sensitivity.
      CONCLUSION: Our results highlight the quantitative discrepancies and limitations
      of the present diagnostic tools in allergy, even when using a single allergenic
      molecule. The quantity of allergen-specific serum IgE is only one component of
      far more complex cellular systems (i.e. basophil-based tests, skin tests) used as
      indirect diagnostic tests for IgE-mediated allergic sensitivity.

PMID- 15725191
TI  - Vaccination for birch pollen allergy: comparison of the affinities of specific
      immunoglobulins E, G1 and G4 measured by surface plasmon resonance.
AB  - BACKGROUND: Allergen-specific immunotherapy (SIT) is associated with increased
      levels of allergen-specific IgG in serum. However, it is not clear to what extent
      qualitative changes in the allergen binding capacity of IgG may be induced as
      well. OBJECTIVE: The purpose of this study was to investigate the influences of
      SIT on antibody affinity. METHODS: The binding affinity of purified serum IgG1,
      IgG4 and IgE to the major allergen in birch (Betula verrucosa) pollen, Bet v 1,
      was analysed by surface plasmon resonance. The antibodies were obtained from 10
      birch pollen-allergic patients receiving SIT and from 10 patients with no SIT.
      RESULTS: The patients having received SIT have a significant higher titre of anti
      Bet v 1 antibodies in their blood, but the affinity to Bet v 1 of allergen
      specific IgE, IgG1 and IgG4 does not differ between the two groups. For IgG1 and
      IgG4, correlations between less allergic symptoms and affinity of the antibodies
      were observed both in the SIT group and to a smaller extent in the non-SIT group.
      CONCLUSION: SIT has no effect on antibody affinity of allergen-specific IgE, IgG1
      or IgG4. Allergic patients with high-affinity IgG1 and IgG4 antibodies report
      less symptoms than patients with low-affinity antibodies.

PMID- 15725192
TI  - Individuals with occupational allergy to detergent enzymes display a differential
      transcriptional regulation and cellular immune response.
AB  - BACKGROUND: In spite of significant safety measures, allergy to industrial
      enzymes remains a major concern. The increasing prevalence of occupational
      allergy emphasizes the need to investigate the functional properties of enzyme
      exposed dendritic cells (DCs), as DCs possess a potent ability to activate
      allergen-specific T cells. OBJECTIVE: This study aims at elucidating the
      molecular mechanisms underlying allergic immune responses to lipase, an
      industrial enzyme. For this purpose, we studied the effect of both hypoallergenic
      and wild-type lipase on the transcriptional regulation in DCs and their
      stimulatory effect on memory CD4+ T cells. METHODS: Five individuals with
      documented lipase allergy were tested for specific serum IgE. DCs from these
      individuals, stimulated with lipases, were assayed for their ability to affect
      proliferation and polarization of memory T cells. The effect of lipases on
      transcriptional activity in DCs was evaluated using global expression analysis.
      RESULTS: Lipase-specific IgE levels varied considerably between donors, with
      donor 4 exhibiting highest levels, and a potent specific CD4+ T cell recall
      response was demonstrated only for donor 4. No difference was detected in
      cytokine profile when T cells from donor 4 were co-cultured with DCs pulsed with
      either hypoallergenic or wild-type lipase, as demonstrated by high IL-4 and IL
      13, and low IFN-gamma production. However, the lipases induced different genetic
      signatures in DCs from donor 4, as compared with the non-responders. CONCLUSIONS:
      DCs from individuals with clinically diagnosed allergy to lipase displayed a
      differential response to stimulation with hypoallergenic and wild-type lipase in
      vitro. Only allergen-pulsed DCs from donor 4 were able to induce CD4+ T cell
      proliferation. The lipase-specific T cells displayed a T-helper type 2 phenotype,
      which was not altered by hypoallergenic lipase-pulsed DCs. Furthermore, DCs
      derived from donor 4 and stimulated with either of the lipases displayed
      different transcriptional profiles, as compared with the other donors. These
      signatures represent genes of potential importance for an immunoregulatory role
      of DC in an ongoing allergic response.

PMID- 15725193
TI  - Oral antihistamines for the symptom of nasal obstruction in persistent allergic
      rhinitis--a systematic review of randomized controlled trials.
AB  - BACKGROUND: Oral antihistamines are recommended by a World Health Organisation
      working group as a first-line pharmacological treatment in mild persistent
      allergic rhinitis. There is, however, uncertainty with respect to their
      effectiveness for a common symptom, that of nasal obstruction. OBJECTIVE: To test
      the null hypothesis that oral antihistamines have no effect on the symptom of
      nasal obstruction in a clinical setting in patients with persistent allergic
      rhinitis. METHODS: Protocol based review of double-blind randomized controlled
      trials of oral antihistamine (i.e. drugs considered to act as a histamine
      receptor type-1 antagonist) vs. placebo. A search was carried out for published
      and unpublished trials. Individuals had to be age 12 years or older (with a
      diagnosis confirmed by skin prick tests, IgE blood tests or nasal allergen
      challenge), experiencing their normal allergen exposure. A symptom score for
      nasal obstruction had to be recorded. Predetermined quality criteria were
      applied. Treating their data as 4-point scores, a meta-analysis was carried out
      for studies, which provided enough data to be pooled. RESULTS: Meta-analysis
      found a weighted mean difference of -0.52 in favour of treatment for patient
      assessed symptom scores (95% confidence interval (CI)-0.73,-0.31, P<0.00001), and
      of -0.33 in favour of treatment for healthcare worker assessed scores (95% CI 
      0.49, -0.16, P = 0.0001). CONCLUSION: Oral antihistamines cause statistically
      significant improvement in the symptom of nasal obstruction in patients with
      persistent allergic rhinitis.

PMID- 15725194
TI  - The effect of treatment with montelukast on in vitro interleukin-10 production of
      mononuclear cells of children with asthma.
AB  - BACKGROUND: The effects of leukotriene modifiers on IL-10 production have not
      been studied in children with asthma. OBJECTIVE: The primary objective of this
      study was to determine the changes in IL-10 concentrations, clinical efficacy and
      peripheral blood eosinophil counts after treatment with montelukast. METHODS: The
      study was conducted on 27 patients: 13 patients monoallergic to grass pollen
      during the pollen season (GPs group) and out of the pollen season (GPos group),
      and on 14 patients monoallergic to house dust mite (HDM) from May to September
      (HDM group). Main outcome measures were changes in concentrations of IL-10 in the
      supernatant after a 4-week treatment with montelukast. Measurements of asthma
      severity score, forced expiratory volume in 1 s (FEV1) and peripheral blood
      eosinophil counts were the secondary end-points. RESULTS: Montelukast resulted in
      a within-group significant increase in IL-10 concentration in the supernatant in
      the GPs (54.0 vs. 125.5 pg/mL) and in the HDM (51.2 vs. 77.1 pg/mL) group.
      Montelukast had no effect on changes of IL-10 concentration in the supernatant
      from peripheral blood mononuclear cell (PBMC) culture after non-sensitizing
      allergen stimulation. Montelukast significantly improved asthma control and FEV1,
      and significantly decreased eosinophil blood count in the GPs and in the HDM
      group after a 4-week treatment. Montelukast did not lead to changes of all
      measured parameters within the GPos group. CONCLUSION: Montelukast increased IL
      10 concentration in supernatants from sensitizing allergen-stimulated PBMC
      culture obtained from children with asthma monoallergic to grass pollen during
      the pollen season, and from children with asthma monoallergic to HDM.

PMID- 15725196
TI  - Co-cultivation of mast cells and Fc epsilon RI alpha+ dendritic-like cells from
      human hip bone marrow.
AB  - BACKGROUND: Mast cells contribute to the pathogenesis of asthma and allergy
      through the release of a plethora of pro-inflammatory mediators and cytokines.
      Their study is hampered by the difficult access to human tissue samples. Human
      mast cells have been cultured from CD34+ progenitors in the bone marrow of normal
      volunteers following iliac crest bone marrow biopsy but this is invasive. Hip
      bone marrow could provide a more convenient less invasive source of mast cell
      progenitors. OBJECTIVE: To characterize mast cells cultured from human bone
      marrow obtained at routine hip surgery. METHODS: Mononuclear cells were isolated
      from the bone marrow reamings of patients undergoing routine hip replacement
      surgery and were cultured with recombinant stem cell factor (SCF), IL-6 and IL
      10. Cell surface markers were examined using flow cytometry, protease expression
      monitored using immunohistochemistry, histamine measured by radioenzymic assay,
      Ca2+ responses analysed using ratiometric Ca2+ imaging, and ion currents recorded
      via the patch-clamp technique. RESULTS: Mast cells were absent at baseline, but
      accounted for 65 +/- 7% of cells after 8-12 weeks of culture, equating to a mean
      0.6 +/- 0.14 x 10(6) mast cells per culture. Fifty-three percent of tryptase+
      cells also contained chymase. The remaining cells comprised a population of large
      CD1a+ HLA-DR+ and Fc epsilon RI alpha+ cells, most likely dendritic cells. All
      mast cells expressed CD117 and the high-affinity IgE receptor alpha-chain (Fc
      epsilon RI alpha) constitutively, and developed a Ca2+ response following IgE
      dependent activation. These cells exhibited 7.8 +/- 2.9% net IgE-dependent
      histamine release, and demonstrated a similar ion channel profile to human lung
      mast cells. In particular, the intermediate conductance Ca(2+)-activated K+
      channel opened following IgE-dependent activation. CONCLUSIONS: Mast cells grown
      from human hip marrow provide a rich non-invasive source of functionally mature
      mast cells. In addition, this culture system may be useful for the generation of
      Fc epsilon RI alpha+ dendritic cells.

PMID- 15725195
TI  - Increased plasma levels of matrix metalloproteinase-9 are associated with the
      severity of chronic urticaria.
AB  - BACKGROUND: Matrix metalloproteinase (MMP)-9 is produced by many inflammatory
      cells such as macrophages, neutrophils, mast cells, eosinophils and T
      lymphocytes. Activated T cells are capable, through cell-cell contact, of
      inducing MMP-9 expression in human mast cells. OBJECTIVE: To investigate the
      activation status of peripheral CD4+ T cells and the level of MMP-9 in the plasma
      of patients with chronic urticaria (CU), and whether MMP-9 levels are in
      association with CU severity. METHODS: Study subjects included 29 patients with
      CU and 30 healthy control subjects. At the time of assessment, patients were
      divided into subgroups according to urticarial severity. Plasma levels of total
      MMP-9 (free pro-MMP-9 and free MMP-9) were determined by ELISA. CD4+ lymphocytes
      were positively selected with magnetic microbeads. After 48 h of activation, CD4+
      T cells were assayed for both nuclear factor-kappa B (NF-kappa B) expression and
      proliferation. RESULTS: Plasma levels of MMP-9 were found to be significantly
      higher in 29 CU patients compared with 18 healthy controls (186 +/- 174 vs. 31 +/
      21 ng/mL, P<0.0001). We also found a significant correlation between MMP-9
      levels and urticarial severity (r = 0.92, P<0.001). In addition, CD4+ T cells
      from CU patients expressed higher levels of NF-kappa B than CD4+ T cells from
      healthy controls (82 +/- 30 vs. 69 +/- 20 optical density, P = 0.007). Finally,
      as compared with seven healthy individuals, DNA synthesis in CD4+ T cells from
      seven CU patients was found to be significantly elevated (1000 +/- 240 vs. 751 +/
      166 counts per minute, P = 0.01). CONCLUSION: Increased levels of MMP-9 are
      found in CU patients, and particularly among those with severe disease. We also
      demonstrated that CD4+ T cells from such patients are highly activated.

PMID- 15725198
TI  - Will exercising informed consent stop "unfortunate experiments"?

PMID- 15725197
TI  - Molecular cloning of a class IV chitinase allergen from Japanese cedar
      (Cryptomeria japonica) pollen and competitive inhibition of its immunoglobulin E
      binding capacity by latex C-serum.
AB  - BACKGROUND: Japanese cedar (Cryptomeria japonica) pollinosis is one of the most
      prevalent allergic diseases in Japan. Only three C. japonica allergens, Cry j 1,
      Cry j 2, and CJP-6, have been characterized. The full IgE-binding spectrum of C.
      japonica pollen allergens demonstrates that many allergens remain to be
      identified. OBJECTIVE: The aim of this study was to characterize a novel allergen
      with a high frequency of IgE binding. METHODS: The cDNA coding for a high
      frequency IgE-binding protein, designated CJP-4, was cloned from the total mRNA
      of C. japonica pollen. The corresponding native allergen was purified by affinity
      precipitation with colloidal chitin and gel chromatography. The IgE-binding
      ability of purified native CJP-4 was characterized by ELISA and ELISA inhibition.
      RESULTS: The CJP-4 cDNA encoded 281 amino acids with significant sequence
      homology to class IV chitinases. Purified native CJP-4, migrated as a homogeneous
      34-kDa protein on SDS-PAGE, revealed endochitinase activity on native PAGE. The
      purified protein displayed the ability to bind IgE from all patients tested
      (31/31) in ELISA, whereas Cry j 1 bound to IgE at a 71% frequency (22/31). Pre
      incubation with latex C-serum completely inhibited the reaction of pooled sera
      IgE from patients with C. japonica pollinosis and/or latex allergy to purified
      CJP-4. CONCLUSION: We identified CJP-4 as a novel and fourth C. japonica
      chitinase allergen with high IgE-binding frequency. The competitive IgE-binding
      profile between C. japonica chitinase and latex C-serum indicated that C.
      japonica chitinase should be an important pan-allergen in C. japonica pollen.

PMID- 15725199
TI  - Childbearing in U.S. military hospitals: dimensions of care affecting women's
      perceptions of quality and satisfaction.
AB  - BACKGROUND: The U.S. Department of Defense provides medical services for
      approximately 9.1 million beneficiaries, one-half of whom are women. Information
      is lacking about how well the military health system has adopted patient-centered
      approaches for promoting individual choice and preference in a bureaucratically
      structured military hospital. The purpose of this study was to examine women's
      evaluations of maternity care with respect to decision-making, confidence, trust
      in health care providers, and treatment within the military hospital. METHODS:
      The Department of Defense Inpatient Childbirth Survey was mailed to a simple
      stratified random sample of beneficiaries who received maternity care at a
      military hospital between July 1 and September 30, 2001. Data for 11 dimensions
      of women's care and experiences were examined from self-reported assessments of
      2,124 respondents who gave birth at one of 44 military hospitals. A multiple
      logistic regression model was estimated to determine which dimensions of care
      predicted beneficiaries' likelihood to recommend the military hospital to family
      and friends. RESULT: Less than 50 percent of respondents would recommend the
      military hospital to family and friends. Significantly associated with women's
      willingness to recommend their specific military hospital to others were courtesy
      and availability of staff, confidence and trust in provider, treatment with
      respect and dignity, information and education, physical comfort, involvement of
      friends and family, continuity and transition, and involvement in decision
      making. CONCLUSIONS: In a military population, obstetric patients who are treated
      with respect, courtesy, and dignity, are involved in decisions about their care,
      and have established trusting relationships with their practitioners are
      significantly more likely to recommend the military hospital to others. It is
      important for military health care leaders to establish a proactive program of
      patient-centered maternity care. Continuous care, education, support services,
      and a multidisciplinary approach should be integrated to retain and recapture
      obstetric patients who are served in military hospitals in the United States.

PMID- 15725200
TI  - Effectiveness of a counseling intervention after a traumatic childbirth: a
      randomized controlled trial.
AB  - Adverse childbirth experiences can evoke fear and overwhelming anxiety for some
      women and precipitate posttraumatic stress disorder. The objective of this study
      was to assess a midwife-led brief counseling intervention for postpartum women at
      risk of developing psychological trauma symptoms. METHOD: Of 348 women screened
      for trauma symptoms, 103 met inclusion criteria and were randomized into an
      intervention (n = 50) or a control (n = 53) group. The intervention group
      received face-to-face counseling within 72 hours of birth and again via telephone
      at 4 to 6 weeks postpartum. Main outcome measures were posttraumatic stress
      symptoms, depression, self-blame, and confidence about a future pregnancy.
      RESULTS: At 3-month follow-up, intervention group women reported decreased trauma
      symptoms, low relative risk of depression, low relative risk of stress, and low
      feelings of self-blame. Confidence about a future pregnancy was higher for these
      women than for control group women. Three intervention group women compared with
      9 control group women met the diagnostic criteria for posttraumatic stress
      disorder at 3 months postpartum, but this result was not statistically
      significant. DISCUSSION: A high prevalence of postpartum depression and trauma
      symptoms occurred after childbirth. Although most women improved over time, the
      intervention markedly affected participants' trajectory toward recovery compared
      with women who did not receive counseling. CONCLUSIONS: A brief, midwife-led
      counseling intervention for women who report a distressing birth experience was
      effective in reducing symptoms of trauma, depression, stress, and feelings of
      self-blame. The intervention is within the scope of midwifery practice, caused no
      harm to participants, was perceived as helpful, and enhanced women's confidence
      about a future pregnancy.

PMID- 15725202
TI  - Influence of fixed and time-dependent factors on duration of normal first stage
      labor.
AB  - BACKGROUND: No accurate method, clinical or otherwise, currently exists to
      determine the onset of labor precisely. The objective of this study was to
      investigate what influences the duration of first stage labor in women with
      spontaneous labor and childbirth in a nonclinical setting. METHODS: From a
      population-based cohort of 1,448 planned home and birth center births, we
      selected 932 births for absence of pathology, absence of intervention, and
      completeness of data. Duration of first stage labor was analyzed with regression
      analysis for duration data or time-to-event analysis, using a specialized
      Transition Data Analysis software. The effects of fixed (age, parity, education,
      antenatal classes, infant birthweight, first cervical assessment) and time
      varying factors (start of midwifery care, spontaneous rupture of membranes) in
      labor were estimated with piecewise-constant exponential hazard models. RESULTS:
      Of the characteristics immutable at the onset of labor, only parity had a strong
      effect on the duration of first stage labor. Cervical dilatation at first
      assessment and time-varying factors, such as the timing of spontaneous rupture of
      membranes and midwifery care, each had a strong influence on labor duration;
      however, the sequence in which they occurred exerted an even stronger influence.
      First stage labors were much shorter if the membranes ruptured before rather than
      after the start of care. CONCLUSION: With the exception of parity, events
      occurring during labor and their timing have a greater influence on the duration
      of first stage spontaneous labor than elements which are immutable at the onset
      of labor. Trials of interventions to influence the duration of labor need to
      consider not only whether the intervention was applied or not, but also when it
      was applied, if cause-effect relationships are to become properly understood.

PMID- 15725201
TI  - Syrian women's preferences for birth attendant and birth place.
AB  - BACKGROUND: Women's preferences for type of maternity caregiver and birth place
      have gained importance and have been documented in studies reported from the
      developed world. The purpose of our study was to identify Syrian women's
      preferences for birth attendant and place of delivery. METHODS: Interviews with
      500 women living in Damascus and its suburbs were conducted using a pretested
      structured questionnaire. Women were asked about their preferences for the birth
      attendant and place of delivery, and an open-ended question asked them to give an
      explanation for their preferences. We analyzed preferences and their
      determinants, and also agreement between actual and preferred place of delivery
      and birth attendant. RESULTS: Only a small minority of women (5-10%) had no
      preference. Most (65.8%) preferred to give birth at the hospital, and 60.4
      percent preferred to be attended by doctors compared with midwives (21.2%). More
      than 85 percent of women preferred the obstetrician to be a female. The actual
      place of delivery and type of birth attendant did not match the preferred place
      of delivery and type of birth attendant. Women's reasons for preferences were a
      perception of safety and competence, and communication style of caregiver.
      CONCLUSIONS: Most women preferred to be delivered by female doctors at a hospital
      in this population sample in Syria. The findings suggest that proper
      understanding of women's preferences is needed, and steps should be taken to
      enable women to make good choices. Policies about maternity education and
      services should take into account women's preferences.

PMID- 15725203
TI  - Canadian maternity experiences survey pilot study.
AB  - BACKGROUND: The Maternity Experiences Survey is a project of the Canadian
      Perinatal Surveillance System. Its primary objective is to provide insight into
      Canadian women's maternity experiences. A pilot study was conducted in 2002/2003
      to determine to what extent women's reports could be used to assess Canadian
      perinatal health policies and practices, and to test the procedures proposed for
      a national maternity experiences survey. METHODS: A nonrepresentative sample of
      291 mothers was drawn from Canadian birth registration records. Mothers whose
      children had died or were no longer in their care were excluded. Participants
      were interviewed 9 to 11 months postpartum about prenatal, labor, and birth and
      postpartum experiences. RESULTS: The response rate was 86 percent. Respondents
      were generally comfortable answering all questions and identified areas of
      potential strength and weakness in the Canadian maternity care system. They had
      difficulty recalling information on some prenatal tests, and labor and birth
      procedures. The use of birth registrations to draw the pilot sample worked well.
      However, some regions may not be able to provide timely access to birth
      registrations for the purposes of a national survey. CONCLUSIONS: The high
      response rate and women's ability to provide information on a wide range of
      topics demonstrates that a national maternity survey would be an effective method
      of providing important maternal health information. The data collected would
      allow Health Canada to carry out more effective national perinatal health
      surveillance with a view to influencing perinatal health policy and practice.

PMID- 15725204
TI  - Impact of postpartum depression on the mother-infant couple.
AB  - BACKGROUND: Few studies have explored the influence of postpartum depression on
      later life among mothers in Taiwan. The present follow-up study aims to explore
      the effects of postpartum depression on the psychosocial health of mothers and on
      the overall development of their infants. METHODS: Follow-up evaluations were
      carried out on 29 postnatally depressed and 31 nondepressed mothers and their
      infants at 1 year after childbirth. Dependent variables were measured by means of
      five structured questionnaires. RESULTS: Postnatally depressed mothers reported
      significantly higher perceived stress, but lower social support and self-esteem
      than nondepressed mothers at 1 year after childbirth. The participants'
      postpartum depression had no significant effect on their infants' eight
      developmental areas, nor did depression influence their plans about the number of
      children to have in the future. CONCLUSIONS: Postpartum depression may have a
      negative influence on the psychosocial health of women, but it does not appear to
      influence the overall development of their infants and their family planning.

PMID- 15725205
TI  - High parity and adverse birth outcomes: exploring the maze.
AB  - BACKGROUND: Despite extensive literature on the topic, it is uncertain if grand
      (para > or = 5) and great grand (para > or = 10) multiparity are associated with
      adverse birth outcomes. We critically evaluate the evidence for and against the
      existence of adverse maternal and/or fetal outcomes in high parity women.
      METHODS: An electronic search of MEDLINE and other bibliographic databases
      (Current Contents, EMBASE, and CAB) was conducted, and all relevant articles in
      English language were retrieved. RESULTS: Findings on the association between
      high parity and maternal-fetal birth outcomes are not consistent. Although the
      older literature tends to suggest that multiparity is a risk factor for negative
      birth outcomes, more recent reports are not supportive. Comparison across studies
      was further complicated by confounding factors like maternal age, socioeconomic
      status, and levels of prenatal care, as well as by variations in study designs
      and in the definition of parity itself. Furthermore, most studies that examined
      women of extreme parity (para > or = 10) were handicapped by inadequate power.
      CONCLUSIONS: After accounting for quality, culture, and degrees of associations,
      the preponderance of evidence seems to point to possible existence of heightened
      risk for certain medical complications and placental pathologies among women of
      extreme parity. The literature also provides reasonable evidence for a higher
      than-expected likelihood for occurrence of fetal macrosomia with advanced parity.

PMID- 15725207
TI  - Overtreatment of normal childbirth in U.S. hospitals.

PMID- 15725206
TI  - Factors that influence women's decisions about whether to participate in
      research: an exploratory study.
AB  - BACKGROUND: Women are increasingly being asked to consider participating in
      medical research. We sought to investigate views of women who participated in and
      declined to participate in a study that was part of a program of maternity care
      research. METHODS: An exploratory study using focus group interviews and
      semistructured interviews was conducted. A purposive sample of 17 postnatal women
      who had participated in research, from a hospital in the North West of England,
      were interviewed. An open coding mechanism to identify emergent themes was used
      for the analysis of data. RESULTS: Of women who had not declined to participate
      in any research, the following themes were identified: altruism versus self
      protection, enhanced versus inferior care, professional guidance versus self
      direction, and welcome versus unacceptable methodology. Of women who had
      participated in some research but declined to participate in other research, the
      following themes were identified: feeling disempowered by the process, inability
      to believe equipoise existed, and practical inconvenience. CONCLUSIONS: These
      findings suggest that although health care researchers adopt an individualistic
      approach to care, they may fail to adopt a similar approach within research. What
      is important and acceptable to women needs to be ascertained to develop
      appropriate research strategies. This plan will ensure that research is carried
      out to the highest ethical standard, which may increase recruitment rates.

PMID- 15725208
TI  - Sheila Kitzinger's letter from Europe: Moslem values and childbirth.

PMID- 15725212
TI  - Pregnant asylum seekers.

PMID- 15725213
TI  - Proceedings of the Eighth Vienna International Workshop on Functional Electrical
      Stimulation. September 10-13, 2003. Vienna, Austria.

PMID- 15725214
TI  - Muscle fiber regeneration in human permanent lower motoneuron denervation:
      relevance to safety and effectiveness of FES-training, which induces muscle
      recovery in SCI subjects.
AB  - Morphologic characteristics of the long-term denervated muscle in animals suggest
      that some original fibers are lost and some of those seen are the result of
      repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron
      denervated patients enrolled in the EU Project RISE show the characteristics of
      long-term denervation. They present a few atrophic or severely atrophic myofibers
      dispersed among adipocytes and connective tissue (denervated degenerated muscle,
      DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are
      present from 1- to 37-years postspinal cord injury (SCI). After 2- to 10-years
      FES-training the muscle cryosections present mainly large round myofibers. In the
      FES-trained muscles the regenerative events are present, but at a lower rate than
      long-term denervated muscles (myofiber per mm2 of cryosection area: 0.8 +/- 1.3
      in FES vs. 2.3 +/- 2.3 in DDM, mean +/- SD, P = 0.011). In our opinion this is a
      sound additional evidence of effectiveness of the Kern's electrical stimulation
      protocol for FES of DDM. In any case, the overall results demonstrate that the
      FES-training is safe: at least it does not induce more myofiber
      damage/regeneration than denervation per se.

PMID- 15725215
TI  - On the regenerative capacity of human skeletal muscle.
AB  - The proliferative capacity of organotypic muscle stem cells, the satellite cells,
      from nine healthy human donors aged between 2 and 78 years was investigated.
      There was a loss in proliferative capacity with age, but the oldest donors (76,
      78 years) would still be able to replace their musculature several times.
      Depending on frequency of desmin-positive (i.e., myogenic) cells during prolonged
      expansion, myoblast cultures could be designated as stable or unstable. There was
      a weak correlation between mean telomere lengths (estimated by flow-FISH) and
      remaining mean population doublings until senescence. A bimodal distribution of
      mean telomere lengths was apparent in both stable and unstable myoblast cultures
      and could be assigned to populations of differently sized cells. Furthermore, due
      to the presence of nonmyogenic cells with longer telomeres, unstable cultures
      tended to show an increasing rather than decreasing mean telomeric length on
      expansion. Bimodal distributions in myoblast cultures could be due to hitherto
      undefined myoblast populations.

PMID- 15725216
TI  - Functional electrical stimulation of denervated muscles: basic issues.
AB  - Denervating injuries result in flaccid paralysis and severe atrophy of the
      affected muscles. This work reviews the potential for functional restoration of
      such muscles by electrical stimulation, focusing on the basic scientific issues.

PMID- 15725217
TI  - Electrical stimulation of denervated muscles: first results of a clinical study.
AB  - To evaluate the effects of electrical stimulation on denervated muscles in spinal
      cord injured humans, the EU Project RISE was started in 2001. The aims of this
      project are: to design and build sufficient stimulators; to develop stimulation
      protocols by means of mathematical models, animal experiments, and practice in
      humans with denervated lower limbs; to develop examination methods and devices
      for evaluation of electrical stimulation training effects; and to acquire basic
      scientific knowledge on denervated and stimulated denervated muscle. In the
      clinical study 27 spinal cord injured individuals were included, furthermore 13
      pilot patients participated. After a series of initial examinations they
      underwent an electrical stimulation program for their denervated lower limb
      muscles. Some of the patients have already follow up examinations. A marked
      increase of muscle mass and quality was observed, the trophic situation of the
      denervated lower limbs had improved obviously.

PMID- 15725218
TI  - Evaluation of FES-induced knee joint moments in paraplegics with denervated
      muscles.
AB  - The pendulum test was applied to evaluate functional electrical stimulation (FES)
      induced joint moments in paraplegics with denervated muscles. Therefore a
      manipulandum was connected to the knee joint and programmed to elicit gravity
      induced leg oscillations. The FES-induced output torque was compensated for in
      order to keep the leg in a mean vertical position (knee angle 90 degrees ). A
      second-order dynamical model was applied to extract the elastic and viscous
      moments from the recorded leg oscillations. This model provided an almost
      adequate description of the relaxed and FES-contracted states. In the relaxed
      state the elastic moment was 15.3 +/- 2.37 Nm/rad and the viscous moment was 0.41
      +/- 0.21 Nms/rad. The FES-induced elastic moment was 29.4 +/- 28.5 Nm/rad and the
      FES-induced viscous moment was 1.53 +/- 1.03 Nms/rad (N = 10, before FES
      training).

PMID- 15725219
TI  - Determination of the chronaxie and rheobase of denervated limb muscles in
      conscious rabbits.
AB  - Measurements of the rheobase and chronaxie can be used to define the excitability
      of nerves and muscles. The aim of this study was to obtain a record over many
      weeks of changes in the rheobase and chronaxie of denervated rabbit tibialis
      anterior muscle (TA). A custom-built electronic stimulator was implanted into the
      peritoneal cavity of New Zealand White rabbits. Large stainless steel electrodes
      were placed on the denervated TA muscle. Rheobase and chronaxie were measured
      noninvasively at weekly intervals by means of a laptop PC, which communicated
      with the stimulator via a radio-frequency link. At each setting the denervated TA
      was palpated manually to detect the response of the muscle. During the first few
      days after denervation the rheobase increased transiently to 0.8 +/- 0.13 mA,
      approximately twice the value for normal innervated muscle, then decreased to
      normal for the remainder of the experimental period. Chronaxie underwent a
      significant 3-fold increase from 4.5 +/- 1.1 ms to 14.1 +/- 1.1 ms during the
      first two weeks of denervation and remained elevated throughout. The custom-built
      implantable electronic stimulator allowed changes in muscle excitability to be
      studied over a long period of denervation within individual animals, providing an
      accurate assessment of the time course of denervation-induced changes in muscle
      excitability.

PMID- 15725220
TI  - Motor control in the human spinal cord.
AB  - Features of the human spinal cord motor control are described using two spinal
      cord injury models: (i) the spinal cord completely separated from brain motor
      structures by accidental injury; (ii) the spinal cord receiving reduced and
      altered supraspinal input due to an incomplete lesion. Systematic studies using
      surface electrode polyelectromyography were carried out to assess skeletal muscle
      reflex responses to single and repetitve stimulation in a large number of
      subjects. In complete spinal cord injured subjects the functional integrity of
      three different neuronal circuits below the lesion level is demonstrated: first,
      simple mono- and oligosynaptic reflex arcs and polysynaptic pathways; second,
      propriospinal interneuron system with their cell in the gray matter and the axons
      in the white matter of the spinal cord conducting activity between different
      spinal cord segments; and third, internuncial gray matter neurons with short
      axons and dense neuron contact within the spinal gray matter. All of these three
      systems participate continuously in the generation of spinal cord reflex output
      activating muscles. The integration of these systems and their relative degree of
      excitation and set-up produces characteristic functions of motor control. In
      incomplete spinal cord injured patients, the implementation of brain motor
      control depends on the profile of residual brain descending input and its
      integration with the functional neuronal circuits below the lesion. Locomotor
      patterns result from the establishment of a new structural relationship between
      brain and spinal cord. The functions of this new structural relationship are
      expressed as an alternative, but characteristic and consistent neurocontrol. The
      more we know about how the brain governs spinal cord networks, the better we can
      describe human motor control. On the other hand such knowledge is essential for
      the restoration of residual functions and for the construction of new cord
      circuitry to expand the functions of the injured spinal cord.

PMID- 15725221
TI  - Stimulation parameter optimization for FES supported standing up and walking in
      SCI patients.
AB  - Functional Electrical Stimulation (FES) to restore leg movement for standing up
      and walking (stepping) in SCI patients with intact lower motor neuron is used by
      several groups. Usually quadriceps muscles are stimulated for hip and knee
      extension, gluteus muscles for hip stabilization, and the common peroneal nerve
      to elicit the flexion reflex. The requirement to get a natural movement would
      need a huge number of stimulation channels--a request that could be easily
      fulfillled from the engineer's point of view but not from the point of
      practicability since each stimulated muscle requires two skin-attached electrodes
      resulting in a prolonged time for donning and doffing. In the described project a
      newly developed eight channel stimulator that can vary the stimulation parameters
      in many ways and over a wide range is used. The goal is to achieve a natural
      movement with a minimum of surface electrodes by optimizing the stimulation
      parameters. Seven experienced FES users and five unexperienced persons (all
      between Th4-Th11) participate in this study. Standing up can be significantly
      improved by optimizing the time delay between the onset of quadriceps and gluteus
      muscles (0.2-0.4 s) and the duration of the ramp. A 0.2 s delay gives good
      results in heavy patients while slower ramps (0.4 s) are required in slim
      patients. During stepping, gluteus muscle timing is not very crucial. Gluteus
      stimulation is turned off 0.1-0.2 s before quadriceps muscle and with the same
      delay turned on again. Of major influence on the gait quality is the timing
      during heel strike when peroneal stimulation is switched off and quadriceps
      stimulation is turned on. Six patients require 0.0-0.1 s where neither peroneal
      nor quadriceps stimulation is applied, the others require an overlap of 0.1-0.2
      s. Activation of adductor muscles during standing up and during the swing phase
      helps to avoid hip abduction and improves knee trajectories.

PMID- 15725222
TI  - Repetitive painful stimulation produces an expansion of withdrawal reflex
      receptive fields in humans.
AB  - The aims of the present study were to investigate whether temporal summation of
      the nociceptive withdrawal reflex depends on the stimulation site on the sole of
      the human foot, and to characterize the reflex receptive fields (RRF) of lower
      limb muscles to repetitive stimulation. The cutaneous RRFs were assessed in 15
      subjects in sitting position by recording the EMG from five lower leg muscles and
      the kinematic responses (ankle, knee, and hip joints) to repetitive painful
      electrical stimulation. The stimulus consisted of a series of five stimuli
      (frequency: 3 Hz) delivered randomly at 10 different sites on the sole of the
      foot. The size of the reflexes increased generally between the first and the
      second stimulus, however, the increment depended on the stimulation site. In
      tibialis anterior, the RRF covered the distal sole of the foot and gradually
      expanded during the stimulus train. No expansion toward the heel area was
      detected. In soleus, the reflexes were facilitated after the second stimulus at
      all sites and remained in this state until the last stimulus. In vastus
      lateralis, biceps femoris, and iliopsoas a gradual expansion of the RRF was seen,
      resulting in RRFs covering the lateral, distal foot, and part of the proximal
      foot (iliopsoas). Knee and hip flexion were evoked at all sites. Ankle
      dorsiflexion was evoked at the distal foot, while ankle plantarflexion was evoked
      at the heel. The enlargement of the RRF reflects spinal temporal summation
      leading to gradually stronger reflex responses. The degree of temporal summation
      was dependent on stimulation site. The facilitation of the withdrawal reflex
      responses due to repetitive stimulation might have potential applications in the
      rehabilitation engineering field, where these reflexes could be used to assist
      gait of patients with central nervous system injuries.

PMID- 15725223
TI  - Overcoming abnormal joint torque patterns in paretic upper extremities using
      triceps stimulation.
AB  - The goal of this research project was to quantitatively assess whether
      transcutaneous triceps stimulation can overcome the expression of abnormal torque
      patterns in the paretic upper limb of subjects with hemiparetic stroke. Abnormal
      torque patterns consist of strong coupling between shoulder abduction (SAB) and
      elbow flexion (EF) or between elbow extension (EE) and shoulder adduction (SAD)
      torques. Both patterns reduce the active range of motion during arm movements.
      Eight chronic stroke subjects with moderate to severe (Fugl-Meyer assessment
      scores of 21/66-36/66) upper limb motor impairment participated in this study.
      Shoulder and elbow joint torques were measured with a 6-degrees-of-freedom load
      cell under isometric conditions, while the triceps muscle was stimulated to
      generate EE torques. At the same time the subjects were asked to lift up their
      arm to generate different SAB torque levels. The obtained isometric results
      showed that electrical stimulation can overcome abnormal torque patterns in
      chronic stroke subjects while generating SAB. This is likely to have potential
      benefits to increase the reaching workspace of the paretic arm.

PMID- 15725224
TI  - A power efficient electronic implant for a visual cortical neuroprosthesis.
AB  - An integrated microstimulator designed for a cortical visual prosthesis is
      presented, along with a pixel reordering algorithm, together minimizing the peak
      total current and voltage required for stimulation of large numbers of electrodes
      at a high rate. In order to maximize the available voltage for stimulation at a
      given supply voltage for generating biphasic pulses, the device uses monopolar
      stimulation, where the return electrode voltage is dynamically varied. Thus, the
      voltage available for stimulation is maximized, as opposed to the conventional
      fixed return voltage monopolar approach, and impedance is significantly lower
      than can be achieved using bipolar stimulation with microelectrodes. This enables
      the use of a low voltage power supply, minimizing power consumption of the
      device. An important constraint resulting from this stimulation strategy,
      however, is that current generation needs to be simultaneous and in-phase for all
      active parallel channels, imposing heavy stress on the wireless power recovery
      and regulation circuitry in large electrode count systems such as a visual
      prosthesis. An ordering algorithm to be implemented in the external controller of
      the prosthesis is then proposed. Based on the data for each frame of the video
      signal to be transmitted to the implant, the algorithm minimizes the total
      generated current standard deviation between time multiplexed stimulations by
      determining the most appropriate combination of parallel stimulation channels to
      be activated simultaneously. A stimulator prototype has been implemented in CMOS
      technology and successfully tested. Execution of the external controller
      reordering algorithm on an application specific hardware architecture has been
      verified using a System-On-Chip development platform. A near 75% decrease in the
      total stimulation current standard deviation was observed with a one-pass
      algorithm, whereas a recursive variation of the algorithm resulted in a greater
      than 95% decrease of the same variable.

PMID- 15725225
TI  - Spastic bladder and spinal cord injury: seventeen years of experience with sacral
      deafferentation and implantation of an anterior root stimulator.
AB  - INTRODUCTION: Spinal cord injured patients with a suprasacral lesion usually
      develop a spastic bladder. The hyperreflexia of the detrusor and the external
      sphincter causes incontinence and threatens those patients with recurrent urinary
      tract infections (UTI), renal failure, and autonomic dysreflexia. All of these
      severe disturbances may be well managed by sacral deafferentation (SDAF) and
      implantation of an anterior root stimulator. MATERIAL AND METHOD: Between
      September 1986 to December 2002, 464 paraplegic patients (220 female, 244 male)
      received a SDAF-SARS. Almost exclusively the SDAF was done intradurally, which
      means with one operation field there can be done two steps (SDAF and SARS).
      RESULTS: 440 patients have a follow-up with 6.6 years (at least > 6 months-17
      years). The complete deafferentation was successful in 94.1%. A total of 420
      paraplegics may use the SARS for voiding (frequency 4.7 per day) and 401 use it
      for defecation (frequency 4.9 per week). Continence was achieved in 364 patients
      (83%). UTI declined from 6.3 per year preoperatively to 1.2 per year
      postoperatively. Kidney function presented stable. Early complications were 6 CSF
      leaks, 5 implant infections. Late complications with receiver or cable failures
      made us do surgical repairs in 34 paraplegics. A step-by-step program for trouble
      shooting differentiates implant failure and myogenic or neurogenic failure.
      CONCLUSION: SDAF is able to restore the reservoir function of the urinary bladder
      and to achieve continence. Autonomic dysreflexia disappeared in most of the
      cases. By means of an accurate adjustment of stimulation parameters it is
      possible to accomplish low resistance micturition. The microsurgical technique
      requires an intensive education. One has to be able to manage late implant
      complications.

PMID- 15725226
TI  - Intraoperative recording of sacral root nerve signals in humans.
AB  - Electroneurographic signals were intraoperatively recorded from the S3 sacral
      nerve root in two SCI patients. The aim of this study was to record afferent
      nerve signals in response to mechanical stimulation of the urinary bladder,
      rectum, and dermatome. Such signals could be used in an implantable
      neuroprosthesis to treat neurogenic detrusor overactivity. In both patients a
      neural response was recorded from the dermatome and the rectum, but from the
      bladder only in one patient. The results were consistent with results from animal
      and other human studies. Further studies are however, needed because the number
      of subjects investigated remains low.

PMID- 15725227
TI  - Electrical stimulation to induce propulsive contractions in the porcine
      descending colon.
AB  - Electrical stimulation of the colon can improve transit in slow-transit
      constipation, or enable controlled emptying in colostomy patients. Preliminary
      studies showed that sequential stimulation of consecutive colon segments induced
      serial contractions resulting in colonic propulsion. This study was performed to
      optimize the stimulation parameters. The electrodes were inserted under the
      serosa of the descending colon of pigs. Charge-balanced rectangular pulses at 10
      Hz were delivered in consecutive sessions. Electrically evoked contractions (ECs)
      were monitored using impedance planimetry and manometry. The luminal pressure and
      cross-sectional area (CSA), the latency and velocity of CSA decrease, and the
      wall tension were compared for ECs induced using 3 ms pulses of 9, 12, 15, and 30
      mA. When using 15 mA, ECs induced by 0.03, 0.3, and 3 ms long pulses were
      compared. A current increase from 9 to 30 mA induced a significant increase in
      the pressure generated by contraction. The increase in pulse duration from 0.03
      to 3 ms resulted in shorter latency, faster contraction, higher pressure, and
      higher wall tension. It is concluded that, at a frequency of 10 Hz, the best
      combination of current and pulse duration to elicit propulsive contractions in
      the descending colon of pigs is 15 mA and 3 ms.

PMID- 15725228
TI  - Numerical investigation of the effects of the clearance gap between the inducer
      and impeller of an axial blood pump.
AB  - A series of numerical models are generated to investigate the flow
      characteristics and performance of an axial blood pump. The pump model includes a
      straightener, an inducer-impeller, and diffuser. Numerical studies of the effects
      of angular alignment of the inducer and impeller blades and the axial clearance
      gap between the inducer and impeller are presented in this article. The pump
      characteristics derived from numerical simulation are validated with experimental
      data. Numerically simulated results showed a sinusoidal variation in the pressure
      generated across the pump with changes in angular alignment between the inducer
      and impeller. This is attributed to additional losses when flow is forced or
      diverted from the trailing edge of the inducer to either the pressure or suction
      side of the impeller blade when the alignment between the two sets of blades is
      not optimal. The pressure generated is a maximum when the impeller blades are at
      0 or 30 degrees with respect to the inducer. The effect of rotating the impeller
      with respect to the inducer causes the sinusoidal pressure variation. In
      addition, it was observed that when the clearance gap between the inducer and
      impeller is reduced to 1 mm, the pressure generated is a minimum when compared to
      the other models. This is attributed to the interference between the inducer and
      impeller when the gap separating them is too small. The location of the maximum
      pressure on the pressure side of the impeller blade shifts upstream while its
      magnitude decreases for small clearance gap between the inducer and the impeller.
      There was no flow separation in the inducer while small regions of backflow are
      observed at the impeller trailing edge. Recommendations for future modifications
      and improvements to the pump design and model simulation are also given.

PMID- 15725229
TI  - Switch from bicarbonate hemodialysis to hemodiafiltration with online
      regeneration of the ultrafiltrate (HFR): effects on nutritional status,
      microinflammation, and beta-microglobulin.
AB  - BACKGROUND: Hemodiafiltration (HFR) with on-line regeneration of the
      ultrafiltrate, a technique of hemodiafiltration in which the ultrafiltrate passes
      through a cartridge containing uncoated charcoal, has been shown to be safe,
      simple, and well tolerated and has been claimed to improve nutritional status or
      to prevent its deterioration while decreasing the inflammatory response via a
      reduced production of proinflammatory cytokines. The purpose of the present
      prospective study was to ascertain whether HRF improves the nutritional status,
      reduces microinflammation, and decreases serum beta2-microglobulin levels in
      patients with end-stage renal disease (ESRD). METHODS: Eight patients, four males
      and four females, with a mean age of 49.4 +/- 16.8 years, stable on hemodialysis
      over a period of 8.7 +/- 6.1 years and on standard 4-4.5 h three-times-a-week
      bicarbonate hemodialysis, were switched to three-times-a-week, 4-h HFR. At
      baseline and every two months for 12 months at mid-week, serum levels of urea,
      creatinine, albumin, total cholesterol, C-reactive protein, fibrinogen,
      complement, ferritin, beta2-microglobulin, intact parathyroid hormone (PTH),
      hemoglobin concentrations, and hematocrit and the EPO weekly dose were
      determined. At baseline and at the end of the study, the Malnutrition
      Inflammatory Score (MIS) was calculated. RESULTS: Nutritional and inflammatory
      parameters remained constant during the 12-month period of the study. After 12
      months of HFR, the MIS trended to be lower, but the difference was not
      statistically significant. Serum beta2-microglobulin and PTH levels remained
      constant during all time intervals. Neither hematocrit nor hemoglobin changed
      over the course of the study as well as the weekly EPO dose. CONCLUSION: The
      change from bicarbonate hemodialysis to HFR was safe and well tolerated but was
      not associated with an improvement of nutritional and inflammatory parameters or
      a reduction of serum beta2-microglobulin levels.

PMID- 15725230
TI  - The SlideReactor--a simple hollow fiber based bioreactor suitable for light
      microscopy.
AB  - Most bioartificial liver support systems are based on hollow fiber capillaries
      within modified dialysis cartridges or more sophisticated bioreactor
      constructions. Due to their design microscopic follow-up of reorganization and
      growth of tissue between the hollow fibers is not possible. The SlideReactor is a
      simple hollow fiber based bioreactor construction suitable for light microscopy
      and time-lapse video observation. The SlideReactor offers a cell compartment
      separated from a medium inflow and outflow compartment. Cell compartment access
      ports enable easy filling of the cell compartment with cell suspension, as well
      as fixation of the tissue. For more complex procedures or full access to all the
      cells, the bioreactor can be opened easily by cutting the silicone seal with a
      scalpel. Due to its simple design and the utilization of standard materials, it
      could serve as a suitable, cost-efficient tool to evaluate the behavior of cells
      cultured between hollow fiber capillaries. The paper describes the production
      process: similar to open source projects in software engineering, we would like
      to propose the concept as an open platform to anyone interested in hollow fiber
      based cell culture.

PMID- 15725231
TI  - Artificial organs 2004: a year in review.

PMID- 15725232
TI  - The expanding role of topical tacrolimus in dermatology.

PMID- 15725233
TI  - Optimizing the cut in Mohs' micrographic surgery in regard to skin sparing and
      microscopic view: is a round incision cut necessary?
AB  - Saucer incision is the common cut in Mohs' micrographic surgery. To date no proof
      as to the superiority of this cut over other patterns has been presented. In this
      work we examine the round pattern aspect of the saucer incision and answer two
      questions: does the round cut provide the best skin-sparing pattern? And, does it
      provide the best microscopic view? A two-dimensional geometric analysis is used
      to determine whether a round incision is optimal from the standpoint of skin
      sparing and microscopic view. Mohs' micrographic surgery views are used to back
      up the geometric hypothesis. The result is that the round incision pattern is
      skin-wasteful compared to an incision that follows the cancerous lesion. In the
      lesion presented here the two cuts have a ratio of 1.5 between the two excised
      skin areas, indicating a waste of healthy skin of 50%. It is also shown that
      specimens with a pointed edge provide better layer projection. The conclusion is
      that a tailored cut following the lesion pattern is the optimal Mohs' incision.
      Therefore in the first stage of Mohs' micrographic surgery the skin cut should
      replicate the lesion pattern instead of a round saucer cut. Though many Mohs'
      surgeons already implement this philosophy, in the literature the saucer incision
      recommended by Dr. Frederic Mohs' remains the norm.

PMID- 15725234
TI  - Cutaneous sarcoidosis in Asians: a report of 25 patients from Singapore.
AB  - Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin
      involving multiple organ systems. There has been no report so far to describe the
      epidemiological pattern of cutaneous involvement in sarcoidosis in South-East
      Asia with diverse ethnic groups. A retrospective study examining the
      clinicopathological features of all patients diagnosed with sarcoidosis at a
      tertiary dermatology centre in Singapore from 1980 to 2003 was conducted.
      Cutaneous sarcoidosis was diagnosed in 25 patients: 13 were Indian, 11 were
      Chinese and one was Eurasian. Cutaneous manifestations included papules, nodules,
      plaques and scarring alopecia. Extracutaneous involvement of lymph nodes (four
      patients), lungs (eight patients) and eyes (two patients) was seen. Eight
      patients had abnormal chest radiographic findings. Histopathological examination
      of skin lesions revealed noncaseating, epithelioid granulomatous infiltration in
      the dermis without evidence of mycobacterial infection, deep fungal infection or
      polarizable birefringent material. Treatment modalities included corticosteroids,
      hydroxychloroquine, isotretinoin, methotrexate and surgical excision. Five
      patients had complete resolution of the cutaneous lesions. Cutaneous sarcoidosis
      is rare in Asia and indeed in Singapore. Extracutaneous involvement is not
      uncommon and a thorough clinical evaluation should be undertaken.

PMID- 15725236
TI  - Multiple dermatofibromas associated with lupus profundus.
AB  - We report a 58-year-old Afro-Caribbean woman who presented with more than 20
      dermatofibromas on the body particularly on the back, arms and legs. These
      developed spontaneously over the course of 5 years. She also had a long-standing
      5 x 2-cm area of lipoatrophy on the right upper arm and a 2-year history of
      several inflammatory subcutaneous nodules developing on the upper chest and left
      breast. These were confirmed histologically as lupus profundus. Apart from a mild
      arthritis, she had no other markers for systemic lupus erythematosus and was
      systemically well. Multiple dermatofibromas are rare. There are around 30 reports
      of multiple dermatofibromas associated with systemic diseases. More than half of
      these cases were associated with systemic lupus erythematosus, with or without
      systemic steroid therapy and about one-third were associated with HIV infection.
      Although the mechanism is unknown, it appears that multiple dermatofibromas are
      associated with autoimmune diseases or altered immune states. This is the first
      case of multiple dermatofibromas associated with lupus profundus. The knowledge
      of such associations may contribute to the understanding of the pathogenesis of
      dermatofibromas, which is as yet unknown.

PMID- 15725235
TI  - Serum immunoglobulins in psoriatic erythroderma.
AB  - The cause of psoriatic erythroderma (PE) is still unknown. Elevation of serum IgE
      has been reported in erythroderma, and as serum hyper-IgE is Th2 cell dominated
      it is of interest to investigate the serum IgE level in PE. In this study, the
      level of immunoglobulins in the sera of PE patients was analysed by a
      retrospective case-control study using psoriasis vulgaris (PV) patients as
      controls. The PE and PV patients were matched in a 1:3 pattern: the first three
      age and sex matched PV inpatients were selected. All of the subjects were
      nonatopic and without allergic history. The serum IgE level was found to be
      elevated in 81.3% of the PE group, which is much higher than that (6.3%) of the
      controls (odds ratio, 65.0; 95% CI, 11.7-361.2; P < 0.001; chi2 test). The mean
      level of serum IgE was much higher in the PE group (272.38 +/- 207.63 IU/mL vs.
      53.20 +/- 86.05 IU/mL, P < 0.001, Student's t-test). No differences were found
      for other immunoglobulins. These results suggest that in PE the Th1/Th2 cell
      imbalance may be switched from Th1 dominant to Th2 dominant. The exact role of
      serum IgE in PE should be investigated further.

PMID- 15725237
TI  - Reticulate hyperpigmented scleroderma: a new pigmentary manifestation.
AB  - Scleroderma is a systemic disease with a myriad of cutaneous manifestations.
      Pigmentary disturbances have been described in scleroderma. While diffuse
      generalized hyperpigmentation and localized hypopigmentation with perifollicular
      hyper-pigmentation are well recognized, a vascular induced hyperpigmentation has
      only been recently described. In this paper, we report another unrecognized
      pigmentary abnormality in a 48-year-old patient who presented with a reticulate
      hyper-pigmentation affecting the trunk, upper and lower limbs. To our knowledge,
      cutaneous hyperpigmented reticulate scleroderma has not been reported previously.

PMID- 15725238
TI  - Pyoderma gangrenosum outside the context of inflammatory bowel disease treated
      successfully with infliximab.
AB  - A 63-year-old man with chronic lymphocytic leukaemia developed pyoderma
      gangrenosum following minor trauma to the leg. He required intensive inpatient
      management with a multitude of treatments including larval therapy, surgical
      debridement, ciclosporin, methotrexate, thalidomide, pulsed intravenous
      methylprednisolone and high-dose intravenous immunoglobulin, clofazamine and high
      dose oral corticosteroids, none of which were helpful. Treatment complications
      included steroid-induced diabetes, Cushing's syndrome and perforated peptic
      ulcer. The pyoderma remained refractory to treatment and continued to extend
      until he received intravenous infliximab 5 mg/kg at weeks 0, 2 and 6.

PMID- 15725239
TI  - Primary cutaneous ganglioneuroma arising within a seborrheic keratosis: a rare
      association.
AB  - A 75-year-old woman presented to her general practitioner with a keratotic skin
      lesion on her abdomen. Microscopic examination showed an irritated seborrheic
      keratosis. However, further inspection revealed a well-defined dome-shaped area
      in the dermis showing a number of small nerve fibres admixed with relatively few
      mature ganglion cells. Both the spindle cell component and the ganglion cells
      stained positively for S-100 protein, neurofilament protein and CD56 (Leu-19,
      NCAM) by routine immunohistochemistry. Primary cutaneous ganglioneuroma is an
      exceedingly rare benign tumour of the skin with only 13 cases having been
      reported in English literature. We describe the second case of primary cutaneous
      ganglioneuroma associated with seborrheic keratosis.

PMID- 15725240
TI  - Chemotherapy-induced scleroderma: a pleiomorphic syndrome.
AB  - A scleroderma-like disease has recently been described in association with
      taxanes. We present the first case of diffuse scleroderma occurring in a woman
      treated with doxorubicin and cyclophosphamide for breast cancer. The clinical
      pattern of skin involvement and histological alterations were identical to those
      found in the classical form of scleroderma. Skin involvement progressed to affect
      80% of total body area, and subsequently remained unchanged despite progression
      of the underlying cancer, making a paraneoplastic aetiology of the scleroderma
      unlikely. Specific chemotherapeutic agents might be directly responsible for the
      clinical manifestations and the parameters of progression. Analysis of all
      similar case reports defines the particular features and clinical course of this
      phenomenon.

PMID- 15725241
TI  - Congenital erosive and vesicular dermatosis.
AB  - An 8-year-old boy born prematurely at 26 weeks' gestation presented with a
      reticulate scar on the left cheek. This started as an eroded area on day 3
      postpartum, followed by crusting and scarring. There were also linear scars on
      the left forearm, left lower back and abdomen. The clinical picture fits the
      entity of congenital erosive and vesicular dermatosis. This retrospective case
      report delineates the outcome with diagnosis only evident after an 8-year time
      period.

PMID- 15725243
TI  - Porokeratosis in association with lymphoedema.
AB  - We describe four patients in whom porokeratosis coexisted with lympoedema of the
      legs. A possible pathogenetic link between the two disorders is discussed, as
      well as the therapeutic implications and the novel physical sign of lymphoedema
      bulging through the porokeratotic lesions.

PMID- 15725242
TI  - A case of tuberculosis verrucosa cutis--undiagnosed for 44 years and resulting in
      fixed-flexion deformity of the arm.
AB  - Tuberculosis verrucosa cutis (TBVC) is a paucibacillary form of cutaneous
      tuberculosis caused by exogenous re-infection in previously sensitized
      individuals. Here, we report an unusual case of TBVC in a 53-year-old Chinese
      woman that had been present for 44 years and resulted in fixed-flexion deformity
      of her arm and functional disability. The diagnosis was made by a positive
      culture for Mycobacterium tuberculosis and she responded well to antituberculous
      therapy. To our knowledge, this is the first such case of TBVC reported in the
      English literature with sequelae of functional impairment of the arm.

PMID- 15725244
TI  - Cutaneous presentation of recurrence of lymphoepithelioid T-cell lymphoma
      (Lennert's lymphoma).
AB  - Lennert's lymphoma (LL) is a T-cell lymphoma characterized by the presence of
      atypical T lymphocytes, admixed with histiocytes and epithelioid granulomas.
      Patients present with superficial lymph node involvement, mainly in the cervical
      areas; thoracic adenopathies and involvement of deep abdominal lymph nodes are
      rare. Cutaneous involvement is infrequent, reported to occur in only 4-11% of
      patients, and even rarer is the onset of cutaneous lesions as first sign of a
      recurrence. We report a female patient who presented with papules and nodules on
      the trunk and upper limbs as the first manifestation of recurrent LL.

PMID- 15725245
TI  - Seronegative secondary syphilis in an HIV-infected patient.
AB  - Recently, increased rates of syphilis among gay men have been observed in
      American and European cities. It is important to establish the diagnosis because
      syphilis facilitates HIV transmission during the primary and secondary stages
      when sores are open on the skin. However the diagnosis can present a dilemma as
      negative reactions to serological tests may be observed in AIDS patients. We
      report here such a case in which the diagnosis was established on dark field
      examination.

PMID- 15725246
TI  - The mode of topical immunomodulators in the immunological network of atopic
      dermatitis.
AB  - For a long time, therapeutic strategies of atopic dermatitis (AD) have been
      dominated by the application of local or systemic steroids or other
      immunosuppressive agents, which have been limited by their potential for unwanted
      local or systemic side effects. Recently, the use of a new generation of topical
      nonsteroidal, immunomodulatory drugs has revolutionized the therapeutic options
      of this often recalcitrant allergic-inflammatory skin disease. Research work has
      focused on the identification of the exact mode of action and the immune
      specificities of the so-called 'topical immunomodulators' (TIMs) such as
      tacrolimus and pimecrolimus in AD. In addition to the previous findings about the
      mode of action of TIMs on T cells, other target cells of TIMs such as
      keratinocytes, mast cells, eosinophils and dendritic cells have been identified
      recently as potential therapeutic targets. In this overview, we provide a
      research update about the anti-inflammatory and anti-allergic properties of TIMs
      on effector cells of AD that may be involved in the complex pathophysiology of
      AD.

PMID- 15725248
TI  - No evidence of increased serum substance P levels in chronic urticaria patients
      with and without demonstrable circulating vasoactive factors.
AB  - The neuropeptide substance P is a possible candidate as histamine-releasing
      factor in some patients with chronic ordinary urticaria (COU), particularly in
      those with evidence of a nonautoantibody circulating histamine-releasing factor.
      In this study, serum substance P levels were measured by enzyme immunoassay in
      117 COU patients, 40 atopic subjects and 24 normal subjects. In vivo and in vitro
      assays for histamine-releasing factors, autologous serum skin test (ASST) and
      basophil histamine release (BHR) assay, respectively, were performed in all COU
      patients. Mean serum substance P concentration was not significantly different in
      COU patients and in normal subjects; however, significantly higher levels were
      detected in atopic subjects than in COU patients (P < 0.003). ASST and BHR assays
      allowed us to distinguish different subsets of COU patients. Mean serum substance
      P concentration did not vary significantly in the different subsets of patients.
      Nevertheless, interestingly three patients with positive ASST and negative BHR
      assay showed very high substance P levels. These results suggest that substance P
      does not play an important role as histamine-releasing factor in COU in general
      but only in occasional patients in whom it might act as a trigger of urticarial
      symptoms.

PMID- 15725247
TI  - The effect of mizolastine on expression of vascular endothelial cell growth
      factor, tumour necrosis factor-alpha and keratinocyte-derived chemokine in murine
      mast cells, compared with dexamethasone and loratadine.
AB  - It has been shown that many antihistamines may have anti-inflammatory activity in
      addition to being H1 antagonists. Mizolastine (MIZ), a novel antihistamine, might
      also have anti-angiogenesis properties. In this study, we investigated the
      influence of MIZ on proangiogenesis factors, vascular endothelial cell growth
      factor (VEGF), tumour necrosis factor (TNF)-alpha and keratinocyte-derived
      chemokine (KC) in murine mast cells by using ELISA and RT-PCR, as compared with
      dexamethasone (DEX) and loratadine (LOR). Our results show that MIZ is effective
      in the inhibition of KC, VEGF and TNF-alpha release induced by an IgE-dependent
      mechanism, in a time- and dose-dependent manner. The differences between the
      inhibitory effects of the three drugs on these proangiogenic factors were rather
      subtle. Semiquantitative analysis using RT-PCR showed that the three drugs
      significantly reduced VEGF165, VEGF120, TNF-alpha and KC mRNA expression.
      Statistical results revealed that the effect of DEX on VEGF165 mRNA was different
      from that of MIZ or LOR (P < 0.01) and the differences between the three drugs on
      VEGF120, TNF-alpha and KC mRNA were not statistically significant (P > 0.05).
      These findings raise the possibility that MIZ can mediate anti-angiogenesis
      activity and that the effect may depend not only on the inhibition on the levels
      of cytokine proteins but also at the mRNA level.

PMID- 15725249
TI  - Capillary morphogenesis gene-2 mutation in infantile systemic hyalinosis:
      ultrastructural study and mutation analysis in a Taiwanese infant.
AB  - Infantile systemic hyalinosis (ISH) is a very rare infantile stiff-skin syndrome
      characterized by extensive deposits of hyaline material in various organs,
      especially the skin and gingiva. Recent studies identified pathogenic mutations
      in the capillary morphogenesis gene 2 (CMG2) in both ISH and juvenile hyaline
      fibromatosis (JHF). Capillary morphogenesis protein-2 is an integrin-like cell
      surface receptor for laminins and type IV collagen, and may play a key role in
      cell-matrix or cell-cell interactions. We report a case of ISH in a 13-month-old
      Taiwanese girl who manifested progressive joint contractures, recurrent chest
      infections, chronic diarrhoea with severe hypoalbuminemia and ascites, gum
      hypertrophy, and violaceous papules and nodules over the occipital area, neck,
      lumbosacral and anogenital areas since birth. Skin biopsy revealed a thickened
      and hyalinized papillary dermis. Electron microscopy showed abundant
      extracellular fibrillogranular material and active fibroblasts with conspicuous
      Golgi complex filled with fibrillar material. Mutation analysis identified a
      homozygous 1073-1074insC mutation of CMG2 which had been reported in four other
      families and may represent a mutation hot spot.

PMID- 15725250
TI  - Prenatal diagnosis of Herlitz junctional epidermolysis bullosa in nonidentical
      twins.
AB  - Advances in molecular diagnostics have led to the feasibility of DNA-based
      prenatal testing in families at risk for recurrence of severe forms of both
      dystrophic and junctional epidermolysis bullosa. In this report, we describe
      prenatal testing in a woman who previously had a child affected with Herlitz
      junctional epidermolysis bullosa. However, in her second pregnancy, she was found
      to have dichorionic diamniotic twins. DNA analysis of a pathogenic mutation and
      informative intragenic polymorphisms (LAMB3 gene) predicted one fetus to be
      affected and the other unaffected. Selective termination of the affected fetus
      was performed, and pregnancy with the unaffected fetus was continued, leading to
      full term delivery of a healthy girl with no skin blisters. This is the first
      reported case of DNA analysis in a twin pregnancy at risk of Herlitz junctional
      epidermolysis bullosa, with successful diagnosis and selective termination of one
      affected twin.

PMID- 15725251
TI  - Rapp-Hodgkin syndrome and the tail of p63.
AB  - We report the clinical and molecular abnormalities in a 19-year-old woman with
      Rapp-Hodgkin ectodermal dysplasia syndrome. The physical features include mid
      facial hypoplasia, uncombable hair, cleft palate and bifid uvula, lacrimal duct
      obstruction and dry skin. Sequencing of the p63 gene reveals a new heterozygous
      frameshift mutation, 1787delG, in exon 14. The frameshift results in changes to
      the tail of p63 with the addition of 68 missense amino acids downstream and a
      delayed termination codon that extends the protein length by 21 amino acids.
      These changes are predicted to disrupt the normal repressive function of the
      transactivation inhibitory domain leading to gain-of-function for at least two
      isoforms of the p63 transcription factor. The expanding p63 mutation database
      demonstrates that there is overlap between Rapp-Hodgkin syndrome and several
      other ectodermal dysplasia syndromes, notably Hay-Wells syndrome, and that
      characterization of the functional consequences of these p63 gene mutations at a
      molecular and cellular level is likely to provide further insight into the
      clinical spectrum of these developmental malformation syndromes.

PMID- 15725252
TI  - Localized bullous pemphigoid 20 years after split skin grafting.

PMID- 15725253
TI  - Hepatitis C virus-related cutaneous vasculitis in the absence of specific
      antibodies.

PMID- 15725254
TI  - Lupus vulgaris postexanthematicus--a rare variant of lupus vulgaris with sarcoid
      like histopathology.

PMID- 15725255
TI  - An unusual case of latex allergy: contact urticaria from natural rubber latex in
      chocolate bar wrappers.

PMID- 15725256
TI  - Gottron-like papules induced by hydroxyurea.

PMID- 15725257
TI  - No association between atopic dermatitis and the SLC9A3R1-NAT9 RUNX1 binding site
      polymorphism in Japanese patients.

PMID- 15725258
TI  - A brand-like plaque.

PMID- 15725259
TI  - A cluster of papules on the buttock of a teenager.

PMID- 15725260
TI  - An ulcer on the lip.

PMID- 15725261
TI  - Recent advances in rheumatology: biological agents for the treatment of
      rheumatoid arthritis, the progression of psoriatic arthritis, autoantibodies in
      systemic lupus erythematosus.

PMID- 15725262
TI  - The topical treatment of psoriasis.

PMID- 15725263
TI  - Intentional community relationships and global health nursing.

PMID- 15725266
TI  - Project improves access to safe drinking water for children in Uganda.

PMID- 15725265
TI  - Global ICN report says supply of nurses affects health care outcomes.

PMID- 15725267
TI  - INR authors speak out: We can learn so much from our colleagues in other
      countries.

PMID- 15725268
TI  - ICN project to increase nursing's capacity to assist in global TB control.

PMID- 15725271
TI  - Community health development: what is it?
AB  - The Department of Health in Taiwan initiated community health development (CHD),
      a new approach to national community health care. Community-based research and
      evaluation approaches have recently been shifting from 'traditional' research to
      'participatory' research. However, there is vagueness about the theoretical
      foundation of CHD and the appropriateness of using participatory action research
      (PAR) to evaluate CHD. This article explores theoretical concepts of CHD and
      discusses the compatibility of PAR and CHD in the theoretical and philosophical
      foundations. Community health development is a developing and changing process
      that involves both the social and the health contexts. It operates on the basis
      of three approaches to care: primary care, health promotion and community
      development. Partnership and empowerment between community health nurses and the
      community are concurrently involved in the entire process of CHD practice. The
      fundamental tenet of PAR focuses on the development of knowledge through
      partnership and empowerment between the researcher and the community, and the
      creation of critical consciousness leading to necessary action and effective
      change. Unlike empirical community-based research, PAR is flexible enough to
      capture an understanding of the complex social and health phenomena in the CHD
      framework. Furthermore, utilizing the PAR approach is appropriate not only for
      the methodological framework of the CHD evaluation, but also for the enhancement
      of the CHD actualization.

PMID- 15725272
TI  - An international programme in nursing and midwifery: building capacity for the
      new millennium.
AB  - AIM: The global economy is changing rapidly and frequently affects the ability of
      the health sector to respond to a variety of needs. Nurses and midwives are
      reaching across national boundaries to strengthen their ability to improve the
      health of populations. This article describes an innovative programme of
      collaboration among different nations to strengthen the capacity of nurses and
      midwives. BACKGROUND: Over the course of 4 years, nurses and midwives from
      several countries in East Central Europe, Central America, and the Caribbean came
      together in the United States and in Europe to learn about opportunities for
      growth and collaboration to improve professional development, leadership
      capacity, educational and curricular development, and knowledge about
      international health. CONCLUSION: Programme participants reported increased
      capacity to perform their professional roles as a result of their having
      participated in this programme. More capacity building activities are needed to
      further enable nursing professionals to meet the demands for health care around
      the world.

PMID- 15725274
TI  - Nursing and public health in Europe -- a new continuous education programme.
AB  - The aim of this paper is to describe the development of a new education programme
      in public health for nurses in the European Union (EU). The project, 'Development
      of a Continuous Professional Education Programme for Nurses in Public Health', is
      described together with its background and aim, which is to contribute to the
      development of new competencies of nurses in nursing and public health. For the
      development of these competencies, the framework for the programme's guidelines
      is organized around core modules common for all EU countries and elective
      modules, based on national health needs and policies proposed by each country. An
      example of the implementation of the programme from Sweden, where the programme
      has already been offered, is also presented. In addition to the educational
      programme itself, the opportunities for networking for nurses and teachers from
      different countries resulting from this effort are discussed. Finally, the
      evolving nature of public health in nursing is presented in relation to the roles
      that nurses/midwives already perform in various countries and situations, in
      order to point out the potential of this programme's contribution to the
      promotion of health of all European citizens.

PMID- 15725273
TI  - International community health networking project: two year follow-up of
      graduates.
AB  - AIM: This paper presents the perceptions of graduates 2 years post-exchange in a
      USA-European Union funded programme. The primary goal of this 8-week exchange
      programme was to increase cultural knowledge and sensitivity by teaching a common
      module of community health assessment and planning to multi-national groups of
      undergraduate students in four countries. BACKGROUND: Cultural diversity and
      globalization are among the factors that encourage faculty in nursing to develop
      programmes of international exchange for students. The challenge is to combine
      the exchange with the teaching of other courses required by the home institution
      during the same semester. METHODS: Twenty-one graduates of participating USA
      schools responded to an open-ended interview by telephone or email 2 years after
      graduation. Bennett's continuum (1993) of intercultural sensitivity was used to
      assess cultural development. FINDINGS: Graduates overwhelmingly supported
      international education and described its continued impact personally and
      professionally. Gains in cultural sensitivity were perceived as the greatest
      benefit and influence on their practice. The majority of graduates were believed
      to be in Bennett's ethnorelative categories of acceptance and adaptation. The
      depth and breadth of previous cultural experiences, specific host and home
      schools, and previous travel were found to be related to development on the
      intercultural sensitivity continuum. DISCUSSION: Most important are the findings
      from this evaluation that provide insight into the factors enhancing growth of
      intercultural sensitivity. Previous travel, characteristics of the home and host
      institutions, and the opportunity and willingness to be a cultural outsider were
      important influences.

PMID- 15725275
TI  - Jordanian baccalaureate nursing students' perception of their learning styles.
AB  - AIM: The purpose of this descriptive study was to determine Jordanian nursing
      students' perception of their learning styles. METHOD: All nursing students
      enrolled in four universities offering a baccalaureate degree in nursing at the
      time of the research project (n = 420) were approached. A structured self
      administered questionnaire (Autonomous Learner Index) developed by the
      researchers was used for data collection. The questionnaire was pilot tested on a
      sample of nursing students who were not included in the study. The tool was
      reliable with an alpha coefficient of 0.89. FINDINGS: The majority of Jordanian
      nursing students perceived themselves as independent learners. The vast majority
      of students indicated that they have a desire to learn new things, are curious to
      learn, and can identify their goal independently. However, a low percentage of
      students indicated having good study skills, ability to concentrate while
      studying and using their study time efficiently. The two-tailed t-test indicated
      no significant differences at alpha 0.05 levels between students' learning
      preferences and the selected demographic variables. CONCLUSION: Based on the
      study findings, it is suggested that nurse educators should provide positive
      reinforcement of students' active involvement in the learning process, which will
      stimulate continued self-direction. Moreover, courses on study skills, writing
      skills, and literature searching skills should be introduced early in nursing
      curricula.

PMID- 15725276
TI  - Motivation for nurses undertaking a post-registration qualification in Malaysia.
AB  - AIM: To present several key factors that motivated Malaysian registered nurses to
      undertake a post-registration degree through an Australian university. The
      overall research study, from which this paper is drawn, looked at the
      professional learning of Malaysian registered nurses and the subsequent impact on
      their careers. BACKGROUND: In Malaysia, the demand for a degree for Malaysian
      nurses provided the impetus for this offshore post-registration nursing
      programme, developed as a twinning venture between an Australian university and a
      Malaysian private institution. The degree programme was conducted largely in
      Malaysia with a 4-week residential block in Australia. METHODS: As this larger
      research study investigated the graduates' personal perspectives of their
      experiences of this post-registration degree programme, the case study approach
      was the appropriate methodological choice. Twelve Malaysian graduate nurses were
      recruited voluntarily from the first cohort of students who completed the
      Bachelor of Health Science-Nursing (post-registration) 5 years post graduation.
      Ethical procedures were observed. The data were collected through individual,
      semi-structured and focus interviews, which took place in Malaysia and were
      personally tape-recorded and transcribed by the researcher. FINDINGS: The
      motivation for formal learning emanated from the participants' personal and
      professional lives. Within these two domains, four separate but interrelated
      reasons emerged: work-related stimulation and self-growth; compliance with
      management requirements; professional advancement and keeping up with the
      profession; and availability and accessibility. However, in a culture where
      higher education is highly priced and yet scarce, the programmes' availability
      and accessibility were ultimate factors.

PMID- 15725277
TI  - Separation of conjoined twins: experiences of perioperative nurses and their
      recommendations.
AB  - BACKGROUND: Within an 8-month period, an unprecedented and historical first in
      Queensland, Australia, the perioperative nurses were members of teams involved in
      the surgical separation of two sets of conjoined twins. Little is known about the
      (dis)stress that some of these perioperative nurses experienced nor how best to
      support them during such experiences. AIM: The aim of this paper is to report on
      the qualitative study that explored the experiences of those perioperative nurses
      involved in the surgical separation of cojoined twins and from their stories
      propose recommendations to support perioperative nurses who are confronted with
      such workplace experiences. METHODS: Using a narrative methodology, nine
      perioperative nurses shared their stories of being involved in the surgical
      separation of conjoined twins in Australia. Narrative and thematic analyses were
      conducted and recommendations to support perioperative nurses through workplace
      (dis)stress were identified. Participants validated the findings and
      recommendations. FINDINGS: The analyses revealed the themes of professionalism,
      teamwork, 'them vs. us' and emotional loads. DISCUSSION: The sensationalism
      around the rarity of conjoined twins brought an intensive intrusiveness from the
      world media. As a result, secrecy within the hospital about the conjoined twin
      cases created divisions between those perioperative nurses on the teams and those
      not. The processes and outcomes of the two surgical cases were in contrast to
      each other. For some perioperative nurses this caused distress. It is essential
      that professional support is offered in a way in which the perioperative nurse
      can take it up without fear of negative judgement.

PMID- 15725278
TI  - Patterns of community relationship: nurses, non-governmental organizations and
      internally displaced persons.
AB  - BACKGROUND: Internally displaced persons (IDPs) are one of the largest at-risk
      populations in the world. Nurses provide health services to IDPs as staff of non
      governmental organizations (NGO). IDPs are also employed to deliver NGO services.
      The way that NGOs and field staff (nurses and others) interact with employed IDPs
      can enhance or diminish IDP quality of life. AIM: This report describes patterns
      of relationships in a community formed by an American NGO, its field staff and
      IDPs as they worked together in a refugee camp at the Thai-Cambodian border over
      13 years. METHODS: This qualitative case study describes relational patterns from
      the NGO perspective. Content analysis was used to process data from in-depth
      interviews with organizational leaders (n = 4) and organizational documents (n =
      234). FINDINGS: A health care training and service mission, carried out between
      an NGO, its field staff and IDPs, was based on a philosophy that turned programme
      activity and authority over to IDP staff. Over 400 IDPs, assisted by 235 field
      staff, delivered effective health care to 85,000 people over 13 years.
      CONCLUSIONS: Work-centred relationships between NGOs, field staff and IDPs are
      significant; they can be consciously created to promote effective, autonomous IDP
      management of health care.

PMID- 15725279
TI  - Patients with moderate chemotherapy-induced mucositis: pain therapy using low
      intensity lasers.
AB  - BACKGROUND: Intensive cancer therapy normally affects malignant and normal cells
      with high replication rates. Cells in the gastrointestinal tract are therefore
      commonly affected by cytotoxins. This often results in the development of
      chemotherapy-induced oral mucositis (COM). COM is the inflammatory response of
      the oral mucous membrane to the chemotherapy drugs. Low level laser therapy
      (LLLT) has proved to be effective in treating and repairing biologically damaged
      tissue and to reduce pain. LLLT has also proven to be an efficient method for the
      prevention of oral mucositis. OBJECTIVE: To investigate the effect of LLLT on
      pain relief among patients who have developed COM. METHOD: The study was
      performed as a clinical test with a sample consisting of 13 adult patients
      receiving oncology treatment. The patients were treated during a 5-day period,
      and the pain was measured before and after each laser application. The laser used
      was an AsGaAl, with a wavelength of 830 nm and a potency of 250 mW. The energy
      given was 35 J cm(-2). ANALYSIS: The results were analysed using the Wilcoxon
      test. RESULTS: There was a significant (P = 0.007) 67% decrease in the daily
      average experience of pain felt before and after each treatment, confirming that
      LLLT can relieve pain among patients who have developed COM. STUDY LIMITATIONS:
      The low number of COM patients at the hospital did not allow a control group to
      be included in the study, and therefore the results contain a potential placebo
      effect. IMPLICATIONS FOR NURSING CARE: The most important benefit the authors
      consider to be the value for the patients of better and quicker treatment with a
      drastic reduction in painful mucositis.

PMID- 15725280
TI  - A holistic approach to the promotion of older hospital patients' health.
AB  - PURPOSE: To describe how nurses interpreted health promotion related to older
      patients in a medical hospital ward and the presuppositions for this work.
      METHODS: The study had a descriptive and explorative design. Data were created
      through participant observation of five nurses and informal dialogues with four
      nurses working in an infection unit in a small hospital in Norway. The nurses
      where followed during a period of 6 months. The observations and dialogues were
      interpreted and transformed into text. This text was analysed with qualitative
      content analysis and interpreted hermeneutically on three levels: (1) reading the
      text to get an overview of the themes; (2) systematically separating central
      patterns; and (3) highlighting the patterns with examples. FINDINGS: The nurses'
      interpretation of health promotion was closely connected to their interpretation
      of health and holistic nursing. Two main aspects were uncovered in the informal
      dialogues: a biomedically oriented nursing view and a holistically oriented
      nursing view. The observations showed that presuppositions, such as waiting for
      something or somebody, constantly changing situations, complexity and diversity
      in patient cases, influenced the nurses' work in general and also their focus on
      health promotion. The nurses balanced between the biomedical and the holistic
      approach. It seemed to be important for the nurses to be the masters of walking
      on a tightrope and to have professional clinical competence. CONCLUSION: It was
      difficult to find a clear focus on health promotion. The most visible focus was
      on diagnosis and treatment, while the more complex and comprehensive situations
      related to health promotion of older patients seemed to be underprioritized. The
      phenomenon of 'waiting' may be an important issue for further research.

PMID- 15725281
TI  - Experimental nickel elicitation thresholds--a review focusing on occluded nickel
      exposure.
AB  - Nickel (Ni) is the most frequent cause of contact allergy among the female
      population. This makes it interesting to examine thresholds for elicitation under
      different conditions. Even though Ni exposure may be open, occluded, penetrating
      or oral, most dose-response studies in the literature concern single occluded
      application. The aims of this study were to assess thresholds of response by
      making a statistical analysis of available dose-response studies with single
      occluded exposure and comparing the results to thresholds from other modes of
      exposure. 8 occluded Ni dose-response studies were selected based on statistical
      considerations. The statistical analysis showed that 5% of a sensitized
      population react to 0.44 microg Ni/cm2 and 10% react to 1.04 microg Ni/cm2. In
      another study with a single open application, 7.8% of sensitized persons
      responded to a dose x6 higher than the dose to which 10% reacted in occluded
      exposure. When combining the exposure to Ni with an irritant, divagating results
      were found, although the literature shows evidence of an augmented response when
      combining exposure to an allergen and an irritant. The thresholds of penetrating
      exposure were found to be lower than the thresholds of single occluded exposure.
      Comparisons of different kind of exposures across studies are difficult, because
      of differences in the studies, although a comparison could be made by a study
      that compares the different exposures within the same individuals at the same
      time.

PMID- 15725282
TI  - Airborne chemicals cause respiratory symptoms in individuals with contact
      allergy.
AB  - Exposure to fragrance chemicals causes various eye and airway symptoms.
      Individuals with perfume contact allergy report these symptoms more frequently
      than individuals with nickel allergy or no contact allergies. However, the
      associations between contact allergy and respiratory symptoms elicited by
      airborne chemicals other than perfumes are unclear. The study aimed to
      investigate the association between eye and airway symptoms elicited by airborne
      chemicals (other than perfumes) and contact allergy in a population-based sample.
      A questionnaire on respiratory symptoms was posted, in 2002, to 1189 individuals
      who participated in 1997/1998 in a Danish population-based study of allergic
      diseases. Questions about eye and airway symptoms elicited by different airborne
      chemicals and airborne proteins were included in the questionnaire. Data from the
      questionnaire were compared with data on patch testing and prick testing. Having
      at least 1 positive patch test (adjusted odds ratio 1.7, 95% CI 1.2-2.5) was
      associated with the symptoms, and the odds ratio increased with the number of
      positive patch tests (P-value for test for trend <0.05). Bronchial
      hyperreactivity, female sex and psychological vulnerability were independently
      associated with symptoms, but no association was found between prick test
      reactivity to proteins and the symptoms elicited by airborne chemicals.

PMID- 15725283
TI  - Screening for contact allergy to artificial nails.
AB  - 27 patients (26 women and 1 man), all in contact with artificial nails, were
      tested for acrylic compounds, known to be present in nail cosmetics. The patch
      test results obtained in these patients demonstrated that 2-hydroxyethyl
      methacrylate and ethyl cyanoacrylate were the only 2 allergens needed to diagnose
      contact allergy to acrylic-containing nail cosmetics, except for 1 patient who
      reacted only to her nail preparation used and in which we were unable to identify
      the allergen. This concerns clearly a limited number of patients. The purpose
      was, however, to detect the most valuable allergen(s) to be used in a
      dermatologist's practice, in which not all possible allergens can be tested, in
      order to diagnose such cases.

PMID- 15725284
TI  - Dermatitis in a printed-circuit board manufacturing facility.
AB  - Dermatitis complaints are frequently encountered among workers in the
      microelectronics industry and have been associated with a variety of physical,
      chemical and psychosocial causes. Employees working in the silk-screening and
      kiln-drying areas of a printed-circuit board manufacturer complained of recurrent
      itching and rashes. This case report describes those symptoms and the results of
      a brief survey of the affected employees, which provided useful data regarding
      the likely aetiology. A brief epidemiological survey instrument was used to gain
      information regarding the pattern, duration and frequency of employee symptoms.
      Data from the survey were used to identify seasonal variations in symptoms that
      correlated with specific environmental factors in the plant. A brief
      epidemiological investigation using a self-reported symptom survey was an
      efficient tool to catalogue the character, pattern, duration and frequency of
      complaints that correlated with specific environmental factors in the plant
      (temperature and low humidity), which were likely causes of the outbreak.

PMID- 15725286
TI  - Methyldibromo glutaronitrile contact allergy: effect of single versus repeated
      daily exposure.
AB  - Some types of cosmetic products such as hand soaps and creams are commonly used
      several times a day, especially in occupational use situations. Little has
      experimentally been shown of how the daily frequency of the application of an
      allergen in a product influences the allergic response. This study investigates
      the allergic responses elicited in presensitized individuals when exposed to a
      specific amount of allergen applied either in 1 application per day or
      distributed over 4 applications per day. As model allergen, the cosmetic
      preservative methyldibromo glutaronitrile (MDBGN) is used. 19 contact allergic
      individuals and 12 controls participated in a double-blind, randomized use test.
      To areas on the forearms were applied 2 drops either once daily of a solution
      containing 0.04% MDBGN or 4 times a day of a solution containing 0.01% MDBGN. 14
      of 19 patients developed dermatitis following the application of approximately
      equal amounts of MDBGN on both arms. Controls were negative. In this experiment,
      applications of 0.04% MDBGN once daily or 0.01% MDBGN 4 times daily had, in a use
      test, approximately equal capabilities of provoking allergic contact dermatitis.
      This adds new knowledge to the risk assessment and regulation of cosmetic
      allergens. However, these results may be highly allergen dependent, and further
      studies are needed before more general conclusions can be made.

PMID- 15725285
TI  - Short-term effects of alcohol-based disinfectant and detergent on skin
      irritation.
AB  - The most important risk factor for occupational contact dermatitis in hospital
      personnel is the exposure to irritants such as water, detergents and alcohol
      based solutions. This study was undertaken to evaluate the short-term effects of
      repeated exposure to an alcohol-based disinfectant, to a detergent and to an
      alcohol-based disinfectant/detergent alternately. The hardening effect in
      preirritated skin after a 4-week interval was also evaluated. Detergent,
      disinfectant and disinfectant/detergent alternately were applied daily every 15
      min for 6 h for 2 days to the flexor upper arms and forearms of 15 volunteers. A
      control area was included. After 4 weeks, a sodium lauryl sulfate patch was
      applied to each area. Irritant reactions were quantified by visual score,
      transepidermal water loss (TEWL) and skin colour at baseline, D3, D8, D35 and
      D37. As evaluated by clinical assessment, detergent caused more redness of the
      skin than both disinfectant applied alone and disinfectant/detergent alternately
      at D3 and D8, P < 0.001 and P < 0.001, respectively. An increased irritant
      response for detergent as compared to disinfectant alone and
      disinfectant/detergent was confirmed by TEWL and colour evaluations, P = 0.001
      and P = 0.001 and P = 0.006 and P = 0.009, respectively. No hardening effect in
      preirritated skin was found after a 4-week interval. In conclusion, hand
      disinfection with alcohol-based disinfectant or alternate use of
      disinfectant/detergent causes less skin irritation than hand disinfection with a
      detergent. This study evaluated the short-term effects of disinfectant and
      detergent exposure only, and more long-term studies are necessary before
      recommendations can be made.

PMID- 15725287
TI  - Allergic contact dermatitis from salicyl alcohol and salicylaldehyde in aspen
      bark (Populus tremula).
AB  - Salicyl alcohol or 2-methylolphenol is a well-known allergen in phenol
      formaldehyde resins and a strong sensitizer in guinea pigs. There is 1 previous
      report of allergic contact dermatitis from salicyl alcohol in aspen bark. We
      describe a second case with concomitant allergy to salicylaldehyde. An elk
      researcher who had handled leaves from various trees presented with eczema of the
      hands, face, flexures, trunk and extremities. Patch testing showed sensitivity to
      salicyl alcohol, salicylaldehyde, balsam of Peru (Myroxylon pereirae resin),
      aspen wood dust and an extract prepared from the bark of aspen (Populus tremula).
      Weaker reactions were observed to bark extracts of rowan (Sorbus aucuparia), tea
      leaved willow (Salix phylicifolia) and goat willow (Salix caprea). We analysed
      salicyl alcohol and salicylaldehyde in the bark extracts and found the 2
      chemicals in equal amounts, about 0.9 microg/mg in aspen bark and in lower
      concentrations in rowan and the willows. We did not find either of the chemicals
      in the test substance of balsam of Peru (Myroxylon pereirae). Besides salicyl
      alcohol, salicylaldehyde is also recommended to be used to screen for contact
      allergy to aspen. Both of these chemicals should be tested in forest workers in
      areas where aspen is growing.

PMID- 15725288
TI  - Rosacea and contact allergy to cosmetics and topical medicaments--retrospective
      analysis of multicentre surveillance data 1995-2002.
AB  - The role of contact allergy in rosacea has rarely been investigated. In this
      retrospective study, 361 out of 76,697 patients tested and documented by the
      Information Network of Departments of Dermatology between 1995 and 2002 had
      rosacea. Patch tests included standard series and constituents of cosmetics and
      topical medicaments. 118/361 had additionally been patch tested with their own
      cosmetics/medicaments. Positive reactions occurred to nickel (II) sulfate in
      9.3%, fragrance mix in 8.8%, thimerosal in 6.9%, Myroxylon pereirae resin in
      5.9%, potassium dichromate in 4.6% and propolis in 2.8%. Whereas rosacea patients
      had a significantly higher risk of contact allergy to propolis compared to the
      remaining patients, in an age- and sex-adjusted analysis, contact allergy to
      nickel was significantly less frequent in this group. For Lyral, the risk was
      elevated, albeit not significantly. Only 2/329 patients were positive to neomycin
      sulfate and 1/100 to gentamicin sulfate, among the panel of (topical) antibiotics
      tested. Among 118 patients tested with their own products, 3 were tested to
      metronidazole, 1 reacting positively. Irritant or doubtful patch test reactions
      were provoked by various substances (vehicles, oxidants and preservatives of
      various creams), which might also be clinically important, considering the
      heightened sensitivity of rosaceous skin.

PMID- 15725289
TI  - Skin symptoms in the seafood-processing industry in north Norway.
AB  - A survey of occupational skin problems, based on a questionnaire, was carried out
      among 883 workers in different types of seafood-processing industries in northern
      Norway. The prevalence of dry skin, itching, rash/eczema, chapped skin and
      chronic sores was significantly higher among production workers (55.6%) in the
      white fish-, shrimp- and salmon-processing industries, compared to administrative
      workers in the same industries (27.5%). Among production workers, there was a
      significantly higher prevalence of skin symptoms among females (60.2%) compared
      to males (50.1%). A strong sex division of work tasks rather than sex itself may
      explain this. There was no sex difference among administrative workers. Several
      risk factors for skin symptoms to occur are indicated. The workers are exposed to
      raw materials and a mixture of water and juice from the fish or shrimp, salt,
      detergents and disinfectants. Gloves may also cause skin problems. Major risk
      factors believed to cause skin symptoms were contact with raw materials, fish
      juice, water and gloves. The results also indicate that skin symptoms are of
      moderate severity and seldom interfere with working capacity.

PMID- 15725290
TI  - Allergic contact dermatitis due to MDI and MDA from accidental occupational
      exposure.

PMID- 15725291
TI  - Chloracne due to o-dichlorobenzene in a laboratory worker.

PMID- 15725292
TI  - Contact hypersensitivity to topical corticosteroids--frequency of positive
      reactions in patch-tested patients with allergic contact dermatitis.

PMID- 15725293
TI  - Allergic contact dermatitis from topical piketoprofen.

PMID- 15725294
TI  - Contact dermatitis caused by allergy to dorzolamide.

PMID- 15725295
TI  - Emla cream-induced allergic contact dermatitis in a child with thalassaemia
      major.

PMID- 15725296
TI  - Localized erythema multiforme-like contact dermatitis from laundry bar soap.

PMID- 15725297
TI  - Contact dermatitis due to topical cosmetic use of vitamin K.

PMID- 15725298
TI  - Generalized exanthematous reaction with pustulosis induced by topical
      corticosteroids.

PMID- 15725299
TI  - Occupational allergic contact dermatitis in a chemist from ethyl bromoacetate and
      bromoacetonitrile.

PMID- 15725300
TI  - Severe allergic contact dermatitis to paraphenylene diamine in hair dye following
      sensitization to black henna tattoos.

PMID- 15725301
TI  - Occupational contact dermatitis due to a marbler's exposure to benzoyl peroxide.

PMID- 15725302
TI  - Ulcerative irritant contact dermatitis from lindane.

PMID- 15725304
TI  - Inspiration-induced vasoconstrictive responses in dominant versus non-dominant
      hands.
AB  - Single rapid and deep inspirations (inspiratory gasps, IG) result in arteriolar
      vasoconstriction with concomitant transient decreases in skin blood flow that are
      most prominent in fingers and toes. Vascular responses (inspiratory gasp
      responses, IGR) are determined as the maximum percentage reduction in blood flow
      and have been used to assess sympathetic neurovascular function in several
      conditions. Previous studies have described various features of the response but
      there has been no reported systematic investigation of the degree of similarity
      between IGR obtained on dominant and non-dominant hands. This aspect is important
      in procedures that may use IGR to evaluate suspected unilateral sympathetic
      dysfunction of a limb-pair or to test the effectiveness of physiological
      interventions imposed on a single limb of a pair. Thus, the goal of our study was
      to compare IGR magnitudes that were simultaneously determined in paired-fingers
      of dominant and non-dominant hands. In 30 healthy seated subjects, skin blood
      perfusion via laser-Doppler (SBF) was measured on the dorsum of the middle finger
      of both hands while subjects performed three sequential IG at 3-min intervals.
      Analysis of variance for repeated measures revealed no significant difference in
      IGR between dominant (79.3 +/- 11.2%) and non-dominant hands (81.9 +/- 11.6%, P =
      0.965) with an overall IGR of 80.6 +/- 11.4%. These results indicate that hand
      dominance is not a factor that is likely to significantly effect IGR
      differentials determined in paired-limbs.

PMID- 15725306
TI  - Cardiovascular autonomic control in endurance-trained and sedentary young women.
AB  - This study aimed to investigate whether endurance-trained (ET) female athletes
      demonstrate differences in cardiovascular autonomic control compared with
      sedentary controls. Eighteen healthy eumenorrhoeic subjects, nine trained (22.4
      +/- 3 years) and nine sedentary (21.0 +/- 1 years), volunteered for the study.
      Heart rate variability (HRV) and cardiovagal baroreflex sensitivity (BRS)
      measures were adopted to assess cardiac autonomic control. HRV was recorded for
      30 min under both controlled (0.25 Hz) and spontaneous breathing conditions.
      Cardiovagal BRS was assessed using the Valsalva manoeuvre. Analysis of the HRV
      showed a longer R-R interval (1089 +/- 114 ms versus 865 +/- 100 ms; P<0.001) in
      the trained subject but only in the spontaneous breathing condition. Conversely,
      athletes exhibited higher normalized low frequency (LFnu, 44.2 +/- 8.5% versus
      29.5 +/- 6.8%; P<0.001) and lower normalized high frequency (HFnu, 55.8 +/- 8.5%
      versus 69.9 +/- 7.7%; P<0.01) only during the controlled breathing condition,
      consequently the LF/HF ratio was also higher in the trained group in the same
      condition (0.83 +/- 0.3 versus 0.47 +/- 0.1, P<0.01). BRS was significantly lower
      in the ET group (7.95 +/- 4.0 ms mmHg(-1) versus 13.00 +/- 4.4 ms mmHg(-1),
      P<0.05). Further studies are necessary to elucidate the potential role of
      training and altered hormonal profile in the genesis of the observed differences
      in cardiovascular autonomic control between highly trained and sedentary control
      female subjects.

PMID- 15725305
TI  - Learning effect of isokinetic measurements in healthy subjects, and reliability
      and comparability of Biodex and Lido dynamometers.
AB  - The aim of this study was to examine the learning effect during a set of
      isokinetic measurements, to evaluate the reliability of the Biodex System 3 PRO
      dynamometer, and to compare the Biodex System 3 PRO and the Lido Active
      dynamometers on both extension and flexion over the elbow and the knee at 60
      degrees s(-1). Thirteen (nine women, four men) healthy participants were measured
      five times using the Biodex and once using the Lido dynamometer. The intervals
      between the first four tests were 20 min, and 1 week between tests 4 and 5.
      Between Biodex and Lido measurements there was a 20 min time interval. When
      comparing the first five measurements (Biodex), no systematic effect over time
      and an excellent reliability were found with respect to elbow and knee flexion
      and extension. No difference in muscle strength (Nm) between the Biodex and Lido
      was observed for knee flexion (P = 0.59), knee extension (P = 0.18) and elbow
      extension (P = 0.63). However, elbow flexion showed a 14.8% (95% CI: 11.2-18.4%;
      P = 0.0001) higher peak torque on Biodex. In conclusion, no learning effect was
      observed and the Biodex proved to be a highly reliable isokinetic dynamometer. A
      difference was observed when comparing Biodex and Lido on elbow flexion, but the
      difference did not outrange the expected variation found with a typical
      isokinetic measurement, which is why both sets of equipment seem applicable in
      clinical practice.

PMID- 15725308
TI  - Impaired microvascular function related to poor metabolic control in young
      patients with diabetes.
AB  - The purpose of the present study was to identify whether young patients with type
      1 diabetes using modern multiple insulin injection therapy (MIT) have signs of
      microvascular dysfunction and to elucidate possible correlations with various
      disease parameters. Skin blood flow on the dorsum of the foot was measured with
      laser Doppler perfusion imaging in 37 patients (age 10-21 years, disease duration
      6.0-16 years) and 10 healthy controls. Measurements were performed at rest, after
      change in posture (the leg was lowered below heart level) and during
      postocclusive hyperaemia. Following a change in posture blood flow increased
      instead of decreased in a majority of the study subjects. Patients with acute
      HbA1c >7.5% (n = 22) had an increase in skin blood flow at rest and a
      significantly reduced blood flow when the leg was lowered below heart level as
      compared with patients with HbA1c <7.5% (0.26 V versus 0.17 V, P<0.01 and 0.12 V
      versus 0.23 V, P<0.05, respectively) and healthy controls. Following occlusion of
      the macrocirculation for 3 min a small non-significant decrease in the hyperaemic
      response was seen in the patients. The postocclusive hyperaemic response and the
      venoarteriolar reflex were not correlated to duration of disease, long-term
      metabolic control or electrophysiological signs of peripheral nerve dysfunction.
      It is concluded that signs of microvascular dysfunction related to poor metabolic
      control are present in young patients with MIT treatment and rather well
      controlled diabetes. Low resting blood flow levels are suggested to contribute to
      the absence of postural vasoconstrictor response.

PMID- 15725307
TI  - Parasympathetic dysfunction in hypertrophic cardiomyopathy assessed by heart rate
      variability: comparison between short-term and 24-h measurements.
AB  - In this study, we evaluate cardiac autonomic function in hypertrophic
      cardiomyopathy (HCM) by assessing heart rate variability (HRV), comparing a short
      term laboratory method with an ambulatory (24-h) method, in patients with and
      without beta-blockade. Reduced HRV is a risk factor for adverse events in some
      cardiac diseases, but is not a proven risk indicator in HCM. Analysis of HRV has
      been based on either short- or long-term electrocardiographic recordings and
      previous studies in HCM have shown conflicting results. There is no consensus on
      which method to prefer, and we evaluate, for the first time, both short- and long
      term analyses in patients with HCM. Long- and short-term HRV analyses were
      performed in 43 patients with HCM. They were divided in two groups, 22 patients
      on beta-blockade and 21 non-treated patients. As controls, 121 healthy subjects
      were used. Young patients without beta-blockade showed a reduction in HRV
      parameters reflecting parasympathetic function, both in the short- and long-term
      registrations, which was attenuated by beta-blockade. Parasympathetic autonomic
      regulation was found to be impaired in young patients with HCM. This may be of
      clinical relevance as abnormal autonomic function might be a substrate for
      malignant dysrhythmias. The impairment was attenuated by beta-blockade, which
      might indicate a clinically useful effect. We also show that short- and long-term
      methods yield similar results, suggesting that a short-term registration might be
      sufficient to assess HRV in patients with HCM.

PMID- 15725309
TI  - Assessment of ventilation inhomogenity with Krypton SPECT and planar imaging.
AB  - In 29 chronic obstructive pulmonary disease (COPD) patients and nine lung healthy
      volunteers, above the age of 50 years, ventilation defects were examined by
      (81m)Kr planar scintigraphy and (81m)Kr single photon emission computed
      tomography (SPECT) to investigate if SPECT adds information regarding size and
      extent of visually scored ventilation defects, and to correlate the extent of
      defects obtained from the two imaging settings with standard pulmonary function
      tests performed in these patients/volunteers. For testing the reproducibility of
      the visual defect score of (81m)Kr scintigraphy additionally 13 patients
      suspected for pulmonary embolism or lung cancer were included. Each series of
      planar or SPECT studies were read for the extent (% abnormal lung) and severity
      (0-3) of ventilation abnormalities. Seventeen scans were read twice for
      reproducibility studies. The extent of ventilation defect assessed by (81m)Kr
      SPECT was higher than by (81m)Kr planar (slope of regression line 0.60,
      P<0.0001), likewise severity score (rank signed test: P<0.0001). Correlation
      between ventilation inhomogeneity and pulmonary function test (residual volume
      and T(L,CO)) in the COPD group revealed only significance for the SPECT
      acquisition. We found good reproducibility of visual assessment of ventilation
      defect extent (correlation: 0.97, P<0.0001) and severity (Kappa 0.62). In
      conclusion, visual scoring of extent and severity of ventilation defects was
      reproducible. Ventilation defects were better demonstrated with SPECT than planar
      imaging. The correlation to pulmonary function was better with SPECT than planar
      imaging.

PMID- 15725310
TI  - Intradialytic exercise as anabolic therapy in haemodialysis patients -- a pilot
      study.
AB  - Haemodialysis (HD) patients are characterized by muscle wasting and consequently
      decreased physical functioning and poor outcome. This pilot study investigated if
      a novel intradialytic exercise programme could increase lean mass via up
      regulation of the insulin-like growth factor (IGF) system. Nine HD patients were
      assessed before (w-12) and after a 3-month control phase (w0), after a three
      month intradialytic interval training programme using high intensity cycle
      exercise (w12), and after a withdrawal of treatment phase (w24). Body composition
      was determined by dual energy X-ray absorptiometry (DEXA) and bioelectrical
      impedance spectroscopy (BIS); physical functioning by knee extensor strength
      (KES) and 30-s sit stand test (SST); and IGF-I and IGFBP-3 in serum and muscle by
      radioimmunoassay. Despite significant increases in training load (+274%,
      P<0.001), peak power output (+71%, P<0.001) and physical function (KES: +19%,
      P<0.05; SST: +20%, P<0.05) following the intervention phase, lean masses by DEXA,
      intra cellular water by BIS (a surrogate measure of body cell mass) and serum and
      muscle IGFs remained unchanged following training. Although this novel exercise
      programme, utilizing high intensity interval training, was safe, clinically
      feasible and beneficial in terms of physical functioning, the 12 weeks of
      intradialytic cycle exercise failed to reverse the muscle atrophy characteristic
      of this population. Future studies, using primary outcome measures similar to
      those employed in the present study, should investigate other anabolic
      interventions to determine potential treatments for the muscle wasting associated
      with end stage renal disease.

PMID- 15725312
TI  - Bispectral index in pediatrics: fashion or a new tool?

PMID- 15725311
TI  - Heart rate variability in young patients with diabetes mellitus and healthy
      subjects explored by Poincare and sequence plots.
AB  - Autonomic neuropathy is a common complication of the diabetes mellitus (DM). The
      significance of its early diagnosis is very high because the mortality of the
      patients with this complication is elevated. Considering the effort to apply new
      mathematical methods to cardiac dysregulation diagnosis, the major aim of the
      study was to ascertain which of the new heart rate variability (HRV) parameters
      are different in young patients with DM type 1 compared with control group. The
      next aim was to assess the HRV changes during prolonged (40 min) supine rest. The
      heart rate was continuously recorded during supine rest in 17 young patients with
      DM type 1 (10 women, 7 men) aged 22.4 +/- 1.0 years (mean +/- SEM). The control
      group consisted of 17 healthy matched probands. The HRV (time/frequency domains,
      Poincare and sequence plots, sample entropy) was analysed in two intervals - T1
      starting at fifth minute and T2 starting at 30th minute of supine rest. The major
      results of our study are: the reduced Poincare plot pattern measures in the young
      DM group; the lower percentage of points in the third quadrant of sequence plot
      (this parameter was not correlated with the mean heart rate) and significant
      changes in HRV during supine rest in DM group (in contrast to control subjects).
      In conclusion, HRV parameters based on nonlinear dynamics were able to
      distinguish cardiac dysregulation in young patients with DM from the control
      group. The percentage of points in the third quadrant of sequence plot provides
      information that is not dependent on mean heart rate. Poincare and sequence
      plots, together with the rate of HRV changes during supine rest, can provide
      clinically relevant information usable in diagnosis of the cardiac dysregulation.

PMID- 15725313
TI  - Opening the upper airway--airway maneuvers in pediatric anesthesia.

PMID- 15725314
TI  - Children's drawings as a measure of anxiety level: a clinical pilot study.
AB  - BACKGROUND: No simple method exists to distinguish children in need for
      premedication. The present study was planned to detect preoperative anxiety
      levels of children by rating their drawings. METHODS: Sixty ASA I children aged 4
      7 years undergoing adenoidectomy were divided into AGIT and CALM groups according
      to agitation level observed during venous cannulation. All children drew a
      picture at three different times: (i) just after arrival in the day-case unit,
      (ii) 10 min before operation and, (iii) prior to leaving for home. The children
      were also randomized to three premedication groups: group D, rectal diazepam 0.5
      mg x kg(-1); group P, 0.9% NaCl 0.1 ml x kg(-1) rectally; group NT, no
      premedication. Five features (size of the drawing, form of the drawing line,
      colors used, mark of the pen and clarity of the picture) from the children's
      drawings were rated with a 3-point scale. The ratings of each feature were made
      to form a sum score of anxiety ranging from 0 to 10. In the analysis of variance
      for repeated measures both the premedication group and agitation score were taken
      into the model as factors. RESULTS: The anxiety score of the drawings of the
      agitated children (during venous cannulation) was significantly higher already
      after arrival in the hospital [AGIT 4.76 (95% CI: 3.56-5.96) Vs CALM 3.67 (95%
      CI: 2.97-4.37) P = 0.029], but there were no statistical differences between the
      different premedication groups. CONCLUSIONS: When routine sedative premedication
      is not used the drawings of the children might detect the children needing
      sedative premedication.

PMID- 15725315
TI  - Investigation of bacteremia following nasotracheal intubation.
AB  - BACKGROUND: The aim of this study was to detect the risk of bacteremia from
      nasotracheal intubation in children undergoing dental treatment under general
      anesthesia. METHODS: Two 10 ml blood samples were taken, the first as a baseline
      and the second within 30 s following the nasotracheal intubation. The samples
      were inoculated into 5 ml aerobic and 5 ml anaerobic blood culture bottles.
      Following incubation in an automated blood culture system, bacteria were
      identified by using conventional biochemical methods and commercial
      identification systems. Mc Nemar's test was used to assess the findings
      statistically. RESULTS: Of 74 patients only nine (12.3%) had positive blood
      cultures after the intubation and seven of these had been intubated without
      trauma. The incidence of bacteremia was significantly higher after atraumatic
      intubation (7/9) compared with traumatic intubation (2/9) (P < 0.05). The most
      common bacteria in positive cultures were Streptococcus viridans, four of 74
      (5.4%). CONCLUSIONS: Since the occurrence of bacteremia after nasotracheal
      intubation is hazardous for patients at risk for developing infective
      endocarditis, to prevent further complications prophylactic antibiotic treatment
      is recommended.

PMID- 15725317
TI  - One lung ventilation in infants and children: experience with Marraro double
      lumen tube.
AB  - BACKGROUND: Our objective was to evaluate the efficacy of selective bronchial
      intubation and independent lung ventilation during thoracic surgery in children
      up to 3 years, using a double lumen tube. METHODS: We studied retrospective
      (cases 1-6) and prospective cases (7-17) between January 1996 and December 2000
      at the All India Institute of Medical Sciences, New Delhi, India and at
      Fatebenefratelli and Ophthalmiatric Hospital, Milan, Italy. Seventeen children, 1
      day to 3 years of age and weighing 2.7-12 kg, were submitted to thoracic surgery
      for a variety of surgical conditions. Anesthesia was conducted as usual in this
      type of patient and selective intubation was performed using a double lumen tube
      (Marraro Pediatric double lumen tube). During the operation one lung ventilation
      was applied and at the end of surgery the collapsed lung was reexpanded
      independently from the contralateral lung. RESULTS: Six children remained
      intubated with a double lumen tube for between 8 and 48 h and one (case no. 11)
      with a single lumen tube for 24 h, while 10 of the older children were extubated
      on the table. No serious complications during or after surgery were noted and
      after extubation all the children recovered completely without sequelae.
      CONCLUSIONS: The double lumen tube appears to be very effective in allowing one
      lung ventilation in this age group during thoracic surgery.

PMID- 15725316
TI  - Rescue sedation with dexmedetomidine for diagnostic imaging: a preliminary
      report.
AB  - BACKGROUND: Sedation is frequently required during noninvasive radiological
      imaging in children. Although commonly used agents such as chloral hydrate and
      midazolam are generally effective, failures may occur. The authors report their
      experience with dexmedetomidine for rescue sedation during magnetic resonance
      imaging. METHODS: A retrospective chart review was undertaken. RESULTS: The
      cohort included five patients ranging in age from 11 months to 16 years.
      Following the failure of other agents (chloral hydrate and/or midazolam),
      dexmedetomidine was administered as a loading dose of 0.3-1.0 microg x kg(-1) x
      min(-1) over 5-10 min followed by an infusion of 0.5-1.0 microg x kg(-1) x h(-1).
      The dexmedetomidine loading dose required to induce sedation was 0.78 +/- 0.42
      microg x kg(-1) (range 0.3-1.2). The maintenance infusion rate was 0.57 +/- 0.06
      microg x kg(-1) x h(-1) (range 0.48-0.69). The imaging procedures were completed
      without difficulty. No patient required additional bolus administrations or
      changes in the infusion rate. The duration of the dexmedetomidine infusion ranged
      from 30 to 50 min. The mean decrease in heart rate was 13.6 +/- 5.1 b x min(-1)
      (14.3 +/- 5.0% from baseline; P = 0.02), the mean decrease in systolic blood
      pressure was 26.4 +/- 15.2 mmHg (24.6 +/- 12.4% decrease from baseline; P =
      0.004), and the mean decrease in respiratory rate was 1.4 +/- 1.5 min(-1) (7.5 +/
      7.9% decrease from baseline; P = NS). P(E)CO2 exceeded 6.5 kPa (50 mmHg) in one
      patient [maximum 6.6 kPa (51 mmHg)] with a maximum value of 6.0 +/- 0.4 kPa (46
      +/- 3 mmHg). Oxygen saturation decreased from 98 +/- 1 to 95 +/- 1%; P = 0.001.
      No patient developed hypoxemia (oxygen saturation less than 90%). Mean time to
      recovery to baseline status was 112.5 +/- 50.6 min and time to discharge was
      173.8 +/- 83.8 min. CONCLUSIONS: Our preliminary experience suggests that
      dexmedetomidine may be an effective agent for procedural sedation during
      radiological imaging. Its potential application in this setting is discussed and
      other reports regarding its use in pediatric patients are reviewed.

PMID- 15725318
TI  - Pediatric sedation in North American children's hospitals: a survey of anesthesia
      providers.
AB  - BACKGROUND: Information about the existence and organization of pediatric
      sedation services in North America is not available. We conducted a survey to
      collect this information from anesthesiologists at pediatric institutions and to
      identify factors perceived as limiting the development of sedation services.
      METHOD: We electronically mailed a confidential survey about pediatric sedation
      practice to an attending anesthesiologist involved in pediatric sedation at 116
      children's hospitals in the United States and Canada. We identified the
      institutions using Internet resources. Electronic mailing addresses were obtained
      from departmental websites, society membership directories and departmental
      administrators. Our follow-up for nonresponders was by a second e-mail and a
      telephone call. RESULTS: A total of 54 completed questionnaires were received, a
      response rate of 47%. Forty-nine (91%) were received from US hospitals, and the
      remainder from Canadian. Fifty percent of hospitals had a formal pediatric
      sedation service. Fifty-four percent utilized a 'mobile' provider model. Hospital
      credentialing for nonanesthesiologist providers varied between 66 and 76% for
      'deep' and 'conscious' sedation, respectively. A nurse-physician provider
      combination was the most common, utilized in 59% of hospitals. Anesthesiologists
      were the sole sedation providers in 26% of institutions. Propofol was used
      regularly by nonanesthesiologists for sedation of nonintubated (42%) and
      intubated (63%) patients. Eighty-seven percent of institutions reported barriers
      to development of pediatric sedation services. The most common barrier was a
      shortage of providers, particularly anesthesiologists. CONCLUSIONS: Propofol use
      by nonanesthesiologists is common. Addressing the shortage of providers, and
      allocating resources for credentialing providers will encourage further
      development of pediatric sedation practice.

PMID- 15725320
TI  - Anesthesia for pediatric renal transplantation with and without epidural
      analgesia--a review of 7 years experience.
AB  - BACKGROUND: Few objective data exist describing current anesthesia practice for
      pediatric renal transplantation. We describe here, the experience from an
      Australian tertiary pediatric center that has continued an active pediatric renal
      transplantation program after relocation in 1995. Areas of interest include
      preoperative status, fluid management, hemodynamic stability, perioperative
      complications, and the use of epidural analgesia. In particular, the influence of
      perioperative epidural analgesia on hemodynamic stability is addressed. METHODS:
      A retrospective review of anesthesia records of all patients undergoing pediatric
      renal transplantation performed at the Children's Hospital at Westmead (CHW),
      from November 1995 to October 2002 was carried out. RESULTS: Fifty-three
      pediatric renal transplants were performed in 50 patients. Average age and weight
      were 10.2 years (range: 1-18 years) and 31.4 kg (range: 9-66 kg), respectively. A
      total of 14 recipients were less than or equal to 6 years of age. Twenty-four
      children were recipients of cadaveric transplants, 29 children received kidneys
      from living related donors. Few children presented with severe anemia (two
      patients) gross electrolyte abnormalities (three patients) or uncontrolled
      hypertension. Intraoperatively, all children had central venous pressure
      monitoring and only four had invasive arterial blood pressure monitoring. Average
      intraoperative fluid administration was 88 ml x kg(-1) (range: 30-190). Twenty
      three children received blood transfusions intraoperatively. Postoperative
      analgesia was provided using an epidural infusion in 39 patients and an opioid
      infusion/patient controlled analgesia in the remainder. There was a tendency to
      greater hemodynamic stability in the group, which received intra-operative
      epidural analgesia. Half the patients who had epidural analgesia required
      parenteral opioid supplementation. Five patients had postoperative pulmonary
      edema. Minor postoperative adverse events included epidural associated motor
      block (three cases) and opioid related oversedation (one patient). No
      perioperative mortality or major morbidity was recorded. CONCLUSIONS: Anesthesia
      for renal transplantation in pediatric patients at CHW is safe and effective
      using a selected range of drugs and techniques. Pretransplant medical
      optimization, careful preoperative assessment, adequate monitoring and precise
      fluid management together with appropriate postoperative analgesia typify the
      perioperative care of CHW renal transplant recipients.

PMID- 15725319
TI  - Safe and effective sedation and analgesia for bone marrow aspiration procedures
      in children with alfentanil, remifentanil and combinations with midazolam.
AB  - BACKGROUND: Invasive procedures such as bone marrow aspiration in children may be
      painful and cause anxiety. We investigated the efficacy and safety of
      remifentanil (R) alfentanil (A), remifentanil-midazolam (RM), and alfentanil
      midazolam (AM) combinations in providing analgesia and sedation for bone marrow
      aspiration. METHODS: Eighty children undergoing a diagnostic bone marrow
      aspiration whose ages ranged from 5-16 years (mean 9.20 +/- 3.00 years) were
      enrolled in this study. The patients were randomly assigned to one of 4 treatment
      groups. Vital signs, sedation and pain scores, somatic responses (sweating and
      tears) were recorded before, during bone marrow aspiration and after 5 and 15 min
      of the procedure. RESULTS: There were no statistical differences between sedation
      and the CHEOPS scores of the four groups during and after the procedures. The VAS
      scores were significantly higher for group A compared with groups R and RM during
      the procedure (P < 0.008). There were no differences between the VAS scores in
      group AM compared with groups R and RM (P > 0.008). There were also no
      statistical differences among the VAS scores of four groups after the procedure
      (P > 0.008). All patients had adequate sedation and analgesia. None of the
      patients in the study had deep sedation, hypotension, bradycardia, hypoxemia, or
      respiratory depression. CONCLUSIONS: Remifentanil, alfentanil, remifentanil
      midazolam, and alfentanil-midazolam combinations are effective in children and
      can be used safely in bone marrow aspiration which is a brief but painful
      procedure performed in the pediatric patient group.

PMID- 15725321
TI  - The ProSeal laryngeal mask airway in children.
AB  - BACKGROUND: The ProSeal (PLMA) is a new laryngeal mask device with a modified
      cuff to improve the seal and a drain tube to provide access to the
      gastrointestinal tract. We assessed the performance of the size 2 (which has no
      dorsal cuff) and size 3 (which has a dorsal cuff) in terms of insertion success,
      efficacy of seal, tidal volume, gas exchange, fiberoptic position, gastric tube
      placement and frequency of problems. METHODS: Eighty children undergoing minor
      surgery were studied (n = 40, size 2 PLMA, weight 10-25 kg; n = 40, size 3 PLMA,
      weight >25-50 kg). Induction was with remifentanil and propofol. Insertion was
      with the introducer tool and by experienced users. Maintenance was with propofol
      or sevoflurane and pressure controlled ventilation. RESULTS: The first-time and
      overall insertion success rate was 84 and 100%, respectively. Oropharyngeal leak
      pressure was 31 +/- 5 cmH2O. There were no gastric or drain tube air leaks. Tidal
      volume and gas exchange was adequate in all patients, other than two brief
      episodes of hypoxia because of airway reflex activation. The vocal cords and
      epiglottis were visible in 99 and 80%, respectively, via the airway tube. The
      first-time and overall insertion success rate for gastric tube insertion was 87
      and 100%, respectively. During maintenance, the PLMA was removed in one patient
      with airway reflex activation and another required epinephrine for bronchospasm.
      There were no differences in performance between the sizes 2 and 3 PLMA.
      CONCLUSION: The PLMA is an effective airway device in children and isolates the
      glottis from the esophagus when correctly positioned. Despite the lack of a
      dorsal cuff, the performance of the size 2 was similar to the size 3 PLMA in the
      age groups tested.

PMID- 15725322
TI  - Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for
      congenital heart disease.
AB  - BACKGROUND: Postoperative bleeding and blood product requirements can be
      substantial in children undergoing open-heart surgery, and reexploration is
      required in 1% of cases. Recombinant activated factor VII (rFVIIa, NovoSeven,
      NovoNordisk, Denmark) is a hemostatic agent approved for the treatment of
      hemophilic patients with inhibitors to factor VIII or factor IX. It has also been
      used with success in other conditions. We present our experience with rFVIIa
      treatment for uncontrolled bleeding after open-heart surgery in five pediatric
      patients. METHODS: The study group consisted of five patients after open-heart
      surgery with excessive blood loss. The patients were treated with rFVIIa after
      failure of conventional treatment to control the bleeding. Blood loss, blood
      product consumption, and coagulation test results were recorded before and after
      rFVIIa administration. RESULTS: In all cases, blood loss decreased considerably
      after rFVIIa administration (mean 7.8 ml x kg(-1) x h(-1)), almost eliminating
      the need for additional blood products, and the prolonged prothrombin time
      normalized. In two patients with thrombocytopathy, rFVIIa helped to discriminate
      surgical bleeding from bleeding caused by a defect in hemostasis. No side effects
      of rFVIIa treatment were noted. CONCLUSIONS: These cases support the impression
      that RFVIIa is efficient and safe in correcting hemostasis in children after
      cardiopulmonary bypass when other means fail. However, the data are still
      limited, and more extensive research is needed.

PMID- 15725323
TI  - Dexmedetomidine as the primary sedative agent for brain radiation therapy in a 21
      month old child.
AB  - Dexmedetomidine (Precedex is an alpha2 adrenoceptor agonist which is gaining
      popularity as a sedative and anesthetic adjuvant. In this case report,
      dexmedetomidine was used safely and easily to provide sedation for 12 radiation
      therapy sessions in a pediatric patient. It provided smooth induction and fast
      recovery with minimal respiratory depression.

PMID- 15725324
TI  - Perioperative care of the patient with Williams syndrome.
AB  - Williams syndrome, initially described by Williams, Barratt-Boyes, and Lowe in
      1961, consists of characteristic dysmorphic features, congenital heart disease,
      and distinctive behavioral and emotional traits. In addition to acquired and
      congenital heart disease, manifestations in the renal, endocrine,
      musculoskeletal, and central nervous system may have implications during the
      perioperative period. Congenital and acquired heart disease can be a significant
      issue as sudden death, related to abnormalities of the coronary arteries, has
      been reported perioperatively in these patients. The authors present a 7-month
      old infant, previously diagnosed with Williams syndrome, who required anesthetic
      care for repair of subaortic and supravalvular aortic stenosis. The potential
      perioperative implications of Williams syndrome are discussed.

PMID- 15725325
TI  - S(+)-ketamine for long-term sedation in a child with retinoblastoma undergoing
      interstitial brachytherapy.
AB  - We report the case of a 14-month-old child undergoing hourly pulse dose radiation
      therapy (interstitial brachytherapy) for 72 h in whom we employed S(+)-ketamine
      for sedation during spontaneous breathing.

PMID- 15725326
TI  - Recurrent life-threatening bradycardia in a child with retained tracheal stent.
AB  - We report a child with a retained welded tracheal stent scheduled for removal
      developing refractory bradycardia and cardiac arrest during attempt to remove the
      stent. Cardiac massage and pacing were necessary to reestablish circulation. The
      same type of arrhythmia occurred three times in the postanesthetic care unit
      after tracheal suction or coughing.

PMID- 15725327
TI  - Anesthesia for children with Wolf-Hirshhorn syndrome: a report and literature
      review.
AB  - Wolf-Hirshhorn is a rare chromosomal defect syndrome. We present two cases of
      children diagnosed with Wolf-Hirshhorn syndrome, and discuss the ramifications of
      anesthesia for these patients.

PMID- 15725328
TI  - Anesthesia for a child with Alagille syndrome.

PMID- 15725329
TI  - An unusual complication of the LMA cuff.

PMID- 15725330
TI  - Taking Ecstasy... it's child's play!

PMID- 15725331
TI  - Intraoral tracheal tube kinking in a child.

PMID- 15725332
TI  - A simple method to monitor airway pressure during manual ventilation using
      Jackson Rees breathing system.

PMID- 15725334
TI  - The human pineal gland and melatonin in aging and Alzheimer's disease.
AB  - The pineal gland is a central structure in the circadian system which produces
      melatonin under the control of the central clock, the suprachiasmatic nucleus
      (SCN). The SCN and the output of the pineal gland, i.e. melatonin, are
      synchronized to the 24-hr day by environmental light, received by the retina and
      transmitted to the SCN via the retinohypothalamic tract. Melatonin not only plays
      an important role in the regulation of circadian rhythms, but also acts as
      antioxidant and neuroprotector that may be of importance in aging and Alzheimer's
      disease (AD). Circadian disorders, such as sleep-wake cycle disturbances, are
      associated with aging, and even more pronounced in AD. Many studies have reported
      disrupted melatonin production and rhythms in aging and in AD that, as we showed,
      are taking place as early as in the very first preclinical AD stages
      (neuropathological Braak stage I-II). Degeneration of the retina-SCN-pineal axis
      may underlie these changes. Our recent studies indicate that a dysfunction of the
      sympathetic regulation of pineal melatonin synthesis by the SCN is responsible
      for melatonin changes during the early AD stages. Reactivation of the circadian
      system (retina-SCN-pineal pathway) by means of light therapy and melatonin
      supplementation, to restore the circadian rhythm and to relieve the clinical
      circadian disturbances, has shown promising positive results.

PMID- 15725335
TI  - Melatonin generates singlet oxygen on laser irradiation but acts as a quencher
      when irradiated by lamp photolysis.
AB  - Melatonin, a naturally occurring chemical mediator, although assigned a diverse
      range of functions, has attracted interest in recent years because of its ability
      to function as a free radical scavenger. Because of the implications of singlet
      oxygen in neurotoxicity, the objective of the study was to investigate the
      ability of melatonin to quench singlet oxygen generated using laser irradiation
      or lamp photolysis. The results show that melatonin produces radicals upon laser
      irradiation while the lamp photolysis studies show that melatonin is able to
      scavenge singlet oxygen produced by naphthalene. While melatonin is a free
      radical scavenger under biological conditions, it acts as a generator of singlet
      oxygen and or radicals (as PhiDelta is 1.41) when irradiated with laser light,
      implying that it has the potential to be used in photodynamic therapy in the
      destruction of tumors.

PMID- 15725336
TI  - Melatonin enhances the hypoxic response of rat carotid body chemoreceptor.
AB  - Melatonin attenuates carotid chemoreceptor response to hypercapnic acidosis and
      may contribute to the effect of circadian rhythms on the chemoreflex. The purpose
      of this study was to test the hypothesis that melatonin modulates rat carotid
      chemoreceptor response to hypoxia. To examine the effect of melatonin on the
      hypoxic response of the chemosensitive cells, cytosolic calcium ([Ca2+]i) was
      measured by spectrofluorometry in fura-2-loaded type-I (glomus) cells dissociated
      from rat carotid bodies. Melatonin (0.01-10 nm) did not change the resting Ca2+]i
      level of the glomus cells but it concentration-dependently increased peak Ca2+]i
      response to cyanide or deoxygenated buffer. An agonist of melatonin receptors,
      iodomelatonin also enhanced the Ca2+]i response to hypoxia. The melatonin-induced
      enhancement of the Ca2+]i response was abolished by pretreatment with
      nonselective mt1/MT2 antagonist, luzindole, and by MT2 antagonists, 4-phenyl-2
      propionamidotetraline or DH97. These findings suggest that melatonin receptors in
      the glomus cells mediate the effect of melatonin on the chemoreceptor response to
      hypoxia. In addition, melatonin increased the carotid afferent response to
      hypoxia in unitary activities recorded from the sinus nerve in isolated carotid
      bodies superfused with bicarbonate-buffer saline. Furthermore, plethysmographic
      measurement of ventilatory activities in unanesthetized rats revealed that
      melatonin (1 mg/kg, i.p.) increased the ventilatory response to hypoxia. Hence,
      the circadian rhythm of melatonin in arterial blood can modulate the carotid
      chemoreceptor response to hypoxia. This modulation may be a physiological
      mechanism involved in the day-light differences in ventilatory activities.

PMID- 15725337
TI  - Melatonin-induced modulation of glucose metabolism in primary cultures of rabbit
      kidney-cortex tubules.
AB  - The effect of melatonin on glucose metabolism in the presence and absence of
      insulin has been investigated in the primary cultures of renal tubules grown in a
      defined medium. In the absence of glucose in the medium containing 5 microg/mL of
      insulin and 2 mm alanine + 5 mm glycerol + 0.5 mm octanoate, 100 nm melatonin
      stimulated both glucose and lactate synthesis, while in the medium devoid of
      insulin melatonin action was negligible. Melatonin-induced increase in glucose
      and lactate synthesis was accompanied by an enhancement of alanine and glycerol
      consumption. In view of measurements of [U-14C]L-alanine and [U-14C]L-glycerol
      incorporation into glucose, it is likely that melatonin increased alanine
      utilization for glucose production, while accelerated lactate synthesis was
      because of an enhanced glycerol consumption. As (i) 10 nm luzindole attenuated
      the stimulatory action of melatonin on glucose formation and (ii) the indole
      induced a decrease in intracellular cAMP level, it seems likely that in renal
      tubules melatonin binds to ML1 membrane receptor subtype. In view of a decline of
      intracellular fructose-1,6-bisphosphate content accompanied by a significant rise
      in hexose-6-phosphate and glucose levels, melatonin might result in an
      acceleration of flux through fructose-1,6-bisphosphatase probably because of an
      increase in the active, dephosphorylated form of this enzyme. Thus, the
      administration of melatonin in combination with insulin might be beneficial for
      diabetic therapy because of protection against hypoglycemia.

PMID- 15725338
TI  - Dopamine receptor activation in bovine pinealocyte via a cAMP-dependent
      transcription pathway.
AB  - D1- and D2-dopamine receptors in the bovine pineal gland were previously
      identified and characterized. The data indicate that the density of D1-dopamine
      receptors far exceeded that of D2-dopamine receptors. In our previous study, the
      mRNA for both the D1- and D2-dopamine receptors which elucidated the status of
      dopamine and its possible involvement in the pineal function was identified. A
      selective D1-agonist enhanced N-acetyltransferase (NAT) activity and increased
      the melatonin level, whereas, a selective D2-agonist inhibited NAT activity and
      decreased the melatonin level. An attempt has been made in the present study to
      clarify the mechanism of dopamine in controlling melatonin production in bovine
      pineal. The level of intracellular cyclic 3',5'-adenosine monophosphate (cAMP)
      was determined after a 2-hr incubation of bovine pinealocytes with selected
      combinations of drugs. SKF 38393, a selective D1-agonist, enhanced intracellular
      level of cAMP, and its effect was blocked by SCH 23390, a D1-selective
      antagonist. In contrast quinpirole, a selective D2-agonist, inhibited forskolin
      stimulated intracellular level of cAMP while its effect was blocked by a D2
      selective antagonist, spiperone. In addition, the dopamine-dependent
      phosphorylation of the transcription factors, cAMP responsive element-binding
      protein (CREB) was investigated. Immunoblots showed that SKF 38393 enhanced CREB
      phosphorylation and the stimulatory effect was abolished by SCH 23390 whereas
      quinpirole inhibited forskolin-stimulated phosphorylated CREB production and the
      inhibitory effect was prevented by spiperone. Taken together with our previous
      data, the results indicate that activation of D1-dopamine receptor in bovine
      pinealocyte stimulates NAT activity and enhances melatonin level whereas
      activation of D2-dopamine receptor leads to an inhibitory effect and these
      stimulatory and inhibitory effects act, in part, via a cAMP-dependent
      transcription mechanism.

PMID- 15725339
TI  - Effects of temperature on 2-[125I]-iodomelatonin binding to melatonin receptors
      in the neural retina of the frog Rana perezi.
AB  - The present study analyzes the effect of temperature-dependent modifications on
      the binding of the analog 2-[125I]-melatonin to melatonin receptors in isolated
      neural retina membranes from the greenfrog Rana perezi. Association and
      dissociation rate constants (K+1, K-1) were exponentially increased by the assay
      temperature. At 15 degrees C, association and dissociation required several
      hours; meanwhile, at 35 degrees C, rate constants were 100- and 34-fold faster,
      respectively. However, the Kd constant calculated as K-1/K+1 was unmodified by
      the assay temperature. When frogs were acclimated at either 5 or 22 degrees C for
      1 month, K+1, and K-1 constants determined at 15 and 25 degrees C were identical
      in both cold- and warm-acclimated groups. Thus, the binding kinetics of melatonin
      receptors in frog retinas did not shown any thermal compensation. Results from
      saturation curves and pharmacological profiles of melatonin binding sites support
      a lack of effect of assay temperature on the affinity of melatonin receptors in
      the frog retina. The inhibition of [125I]Mel binding by GTPgammaS showed clearly
      that the coupling of melatonin receptors to G proteins is temperature-dependent.
      Higher concentrations of the GTP analog were needed to inhibit specific binding
      when temperature decreased. The temperature effect on binding kinetics and on the
      G protein coupling to melatonin receptors suggests that the melatonin signal
      could be transduced distinctly depending on the temperature. Thus, temperature
      plays a major role, not only on melatonin synthesis, but also in the transduction
      of melatonin signal in ectotherms.

PMID- 15725340
TI  - Corticosterone modulates noradrenaline-induced melatonin synthesis through
      inhibition of nuclear factor kappa B.
AB  - In chronically inflamed animals, adrenal hormones exert a positive control on the
      secretion of melatonin by the pineal gland. In this paper, the mechanism of
      corticosterone as a modulator of melatonin and N-acetylserotonin (NAS) was
      determined. Rat pineal glands in culture, stimulated for 5 hr with noradrenaline
      (10 nm), were previously incubated with corticosterone (1.0 nm-1.0 microm) for 48
      hr in the presence or absence of the glucocorticoid receptor (GR) antagonist,
      mifepristone (1.0 microm), the proteasome inhibitor, N-acetyl-leucinyl-leucinyl
      norleucinal-H (ALLN, 12.5 microm) or the antagonist of the nuclear factor kappa B
      (NFkappaB), pyrrolidinedithiocarbamate (PDTC, 12.5 microm). Corticosterone
      potentiated noradrenaline-induced melatonin and NAS production in a bell-shaped
      manner. The increase in NAS (12.9 +/- 2.7, n=6 versus 34.3 +/- 8.3 ng per pineal)
      and melatonin (16.3 +/- 2.0, n=6 versus 44.3 +/- 12.9 ng per pineal) content
      induced by 1 microm corticosterone was blocked by mifepristone, and mimicked by
      ALLN and PDTC. The presence of GRs was shown by [3H]-dexamethasone binding (0.30
      +/- 0.09 pmol/mg protein) and corticosterone inhibition of NFkappaB nuclear
      translocation was demonstrated by electromobility shift assay. Therefore,
      corticosterone potentiates noradrenaline-induced melatonin and NAS production
      through GR inhibition of NFkappaB nuclear translocation. To the best of our
      knowledge, this is the first time that this relevant pathway for passive and
      acquired immune response is shown to modulate melatonin production in pineal
      gland.

PMID- 15725341
TI  - Environmental control and adrenergic regulation of pineal activity in the diurnal
      tropical rodent, Arvicanthis ansorgei.
AB  - Like nocturnal rodents, the diurnal tropical rodent Arvicanthis ansorgei shows a
      daily rhythm in pineal melatonin content. Seasonal and photoperiodic variations
      in the biosynthetic activity of the pineal gland: arylalkylamine-N
      acetyltransferase (AA-NAT), hydroxyindole-O-methyltransferase (HIOMT) activities
      and melatonin content were measured in male and female A. ansorgei captured near
      Samaya, Mali, and kept either under artificial laboratory photoperiods [light
      dark (LD) cycles: LD 14:10, LD 12:12 or LD 10:14 or caught in the field in Mali
      and killed at four different times of the year (January, April, June and
      November). Under artificial photoperiod, the duration of the nocturnal peak of AA
      NAT activity and melatonin content increased with the duration of the dark period
      while the amplitude did not significantly change. In the field, annual variations
      in the amplitude of the nocturnal melatonin peak were observed with a maximum in
      April (highest temperature, low humidity and no grass availability, only seeds)
      and a minimum in November (high humidity, maximum green grass availability). The
      variations in the amplitude of the melatonin peak were not correlated with
      changes in AA-NAT HIOMT activities, suggesting that seasonal variations in the
      amplitude of the melatonin peak are not driven by these enzymes. Daytime
      injections of the beta-adrenergic agonist, isoproterenol, stimulated melatonin
      synthesis in January, April and June, but not in November. The annual differences
      in the amplitude of the melatonin peak as well as the seasonal differences in the
      response to an adrenergic stimulation suggest that environmental factors other
      than photoperiod, such as temperature, humidity and consequent food availability,
      could be important in the regulation of the annual variations in the pineal
      biosynthetic activity in this species.

PMID- 15725342
TI  - Attenuation in the evolution of experimental spinal cord trauma by treatment with
      melatonin.
AB  - Melatonin is the principal secretory product of the pineal gland and its role as
      an immuno-modulator is well established. Recent evidence shows that melatonin is
      a scavenger of oxyradicals and peroxynitrite and exerts protective effects in
      septic shock, hemorrhagic shock and inflammation. In the present study, we
      evaluated the effect of melatonin treatment, in a model of spinal cord injury
      (SCI). SCI was induced by the application of vascular clips (force of 50 g) to
      the dura via a four-level T5-T8 laminectomy. SCI in rats resulted in severe
      trauma characterized by edema, neutrophil infiltration and apoptosis (measured by
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining).
      Infiltration of spinal cord tissue with neutrophils (measured as increase in
      myeloperoxidase activity) was associated with enhanced lipid peroxidation
      (increased tissue levels of malondialdehyde). Immunohistochemical examination
      demonstrated a marked increase in immunoreactivity for nitrotyrosine and Poly(ADP
      ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a) spinal
      cord inflammation and tissue injury (histological score), (b) nitrotyrosine and
      PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly
      reduced in spinal cord tissue obtained from rats treated with melatonin (50 mg/kg
      i.p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate
      set of experiment we have clearly demonstrated that melatonin treatment
      significantly ameliorated the recovery of limb function (evaluated by motor
      recovery score). Taken together, our results demonstrate that treatment with
      melatonin reduces the development of inflammation and tissue injury events
      associated with spinal cord trauma.

PMID- 15725343
TI  - Melatonin regulates circadian electroretinogram rhythms in a dose- and time
      dependent fashion.
AB  - The circadian rhythm of the chick electroretinogram (ERG) is regulated by the
      indoleamine hormone melatonin. To determine if the concentration of melatonin or
      the time at which it was administered would have differential effects on ERG
      parameters, we conducted experiments analyzing the effects of melatonin at
      different times of the day. Circadian rhythms of a- and b-wave implicit times and
      amplitudes were observed in both light:dark (LD) and in continuous darkness (DD).
      Intramuscular melatonin administration of 1 mg/kg and 100 ng/kg decreased a- and
      b-wave amplitudes and increased a- and b-wave implicit times. This effect was
      significantly greater than that observed for 1 ng/kg melatonin, which had little
      to no effect over the saline controls. The effect of 1 mg/kg and 100 ng/kg
      melatonin on a- and b-wave amplitude in LD and on b-wave amplitude in DD was
      greater during the night (ZT/CT 17) than during the day (ZT/CT 5). The fold
      change in b-wave implicit time over that of controls was greater during the day
      (ZT/CT 5) than during the night (ZT/CT 17). These data indicate that melatonin
      may play a role in regulating a day and night functional shift in the retina, and
      that it does so via regulation of a retinal clock.

PMID- 15725345
TI  - CNS activity of Pokeweed anti-viral protein (PAP) in mice infected with
      lymphocytic choriomeningitis virus (LCMV).
AB  - BACKGROUND: Others and we have previously described the potent in vivo and in
      vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral
      protein) against a wide range of viruses. The purpose of the present study was to
      further elucidate the anti-viral spectrum of PAP by examining its effects on the
      survival of mice challenged with lymphocytic choriomeningitis virus (LCMV).
      METHODS: We examined the therapeutic effect of PAP in CBA mice inoculated with
      intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that
      is lethal to 100% of mice within 7-9 days. Mice were treated either with vehicle
      or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24
      hours, 48 hours 72 hours and 96 hours after virus inoculation. RESULTS: PAP
      exhibits significant in vivo anti- LCMV activity in mice challenged
      intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic
      dose levels, PAP significantly prolonged survival in the absence of the majority
      of disease-associated symptoms. The median survival time of PAP-treated mice was
      >21 days as opposed to 7 days median survival for the control (p = 0.0069).
      CONCLUSION: Our results presented herein provide unprecedented experimental
      evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice.

PMID- 15725346
TI  - The relationships between depression and other outcomes of chronic illness
      caregiving.
AB  - BACKGROUND: Many caregivers with chronically ill relatives suffer from
      depression. However, the relationship of depression to other outcomes of chronic
      caregiving remains unclear. This study tested a hypothesized model which proposed
      that hours of care, stressful life events, social support, age and gender would
      predict caregivers' outcomes through perceived caregiver stress. Depression was
      expected to mediate the relationship between perceived stress and outcomes of
      chronic caregiving (physical function, self-esteem, and marital satisfaction).
      METHODS: The sample for this secondary data analysis consisted of 236 and 271
      subjects from the Americans' Changing Lives, Wave 1, 1986, and Wave 2, 1989, data
      sets. Measures were constructed from the original study. Structural equation
      modeling was used to test the hypothesized model, and an exploratory structural
      modeling method, specification search, was used to develop a data-derived model.
      Cross-validation was used to verify the paths among variables. RESULTS: Hours of
      care, age, and gender predicted caregivers' outcomes directly or through
      perceived caregiver stress (p < .01). Depression mediated the relationship
      between perceived stress and psychological outcomes and explained 40% and 11% of
      the variance in self-esteem and marital satisfaction, respectively. CONCLUSION:
      Depression predicted psychological outcomes. Whether depression predicts physical
      health outcomes needs to be further explored.

PMID- 15725347
TI  - GANN: genetic algorithm neural networks for the detection of conserved
      combinations of features in DNA.
AB  - BACKGROUND: The multitude of motif detection algorithms developed to date have
      largely focused on the detection of patterns in primary sequence. Since sequence
      dependent DNA structure and flexibility may also play a role in protein-DNA
      interactions, the simultaneous exploration of sequence- and structure-based
      hypotheses about the composition of binding sites and the ordering of features in
      a regulatory region should be considered as well. The consideration of structural
      features requires the development of new detection tools that can deal with data
      types other than primary sequence. RESULTS: GANN (available at
      http://bioinformatics.org.au/gann) is a machine learning tool for the detection
      of conserved features in DNA. The software suite contains programs to extract
      different regions of genomic DNA from flat files and convert these sequences to
      indices that reflect sequence and structural composition or the presence of
      specific protein binding sites. The machine learning component allows the
      classification of different types of sequences based on subsamples of these
      indices, and can identify the best combinations of indices and machine learning
      architecture for sequence discrimination. Another key feature of GANN is the
      replicated splitting of data into training and test sets, and the implementation
      of negative controls. In validation experiments, GANN successfully merged
      important sequence and structural features to yield good predictive models for
      synthetic and real regulatory regions. CONCLUSION: GANN is a flexible tool that
      can search through large sets of sequence and structural feature combinations to
      identify those that best characterize a set of sequences.

PMID- 15725348
TI  - Possible role of eclosion rhythm in mediating the effects of light-dark
      environments on pre-adult development in Drosophila melanogaster.
AB  - BACKGROUND: In insects, circadian clocks have been implicated in affecting life
      history traits such as pre-adult development time and adult lifespan. Studies on
      the period (per) mutants of Drosophila melanogaster, and laboratory-selected
      lines of Bactrocera cucurbitae suggested a close link between circadian clocks
      and development time. There is a possibility of clock genes having pleiotropic
      effects on clock period and pre-adult development time. In order to avoid such
      pleiotropic effects we have used wild type flies of same genotype under
      environments of different periodicities, which phenotypically either speeded up
      or slowed down the eclosion clock of D. melanogaster. RESULTS: We assayed pre
      adult development time and pre-adult survivorship of four laboratory populations
      of D. melanogaster, under five different light regimes, continuous light (LL),
      continuous darkness (DD), and light-dark (LD) cycles of 10:10 h (T20), 12:12 h
      (T24), and 14:14 h (T28). Although the development time was significantly
      different in most light regimes, except for females under T24 &T28, pre-adult
      survivorship remained largely unaffected. The development time was shortest under
      LL, followed by T20, DD, T24 and T28 regimes, in that order. Interestingly the
      development time showed a positive correlation with the period of eclosion
      rhythm, i.e., faster oscillations were associated with faster development, and
      slower oscillations with slower development. CONCLUSION: Based on these results
      we conclude that periodicity of imposed LD cycles, and/or of eclosion rhythm
      plays a key role in regulating the duration of pre-adult development in D.
      melanogaster in a manner that does not involve direct pleiotropic effects of
      clock genes on both clock period and development time.

PMID- 15725349
TI  - Consequences of the historical demography on the global population structure of
      two highly migratory cosmopolitan marine fishes: the yellowfin tuna (Thunnus
      albacares) and the skipjack tuna (Katsuwonus pelamis).
AB  - BACKGROUND: Yellowfin and skipjack tuna are globally distributed in the world's
      tropical and sub-tropical oceans. Since little, if any, migration of these fishes
      occurs between the Atlantic and Indo-Pacific Oceans, one might expect to see
      genetic differences between sub-populations in these ocean basins. However,
      yellowfin and skipjack tuna have extremely large population sizes. Thus, the rate
      of genetic drift should be slower than that observed for other tunas. RESULTS:
      Low levels of genetic differentiation were observed between Atlantic and Pacific
      samples of yellowfin tuna. In contrast, no genetic differentiation was observed
      between Atlantic and Pacific samples of skipjack tuna. CONCLUSION: Much lower
      levels of genetic differentiation were found among sub-populations of yellowfin
      tuna compared to those observed for other large tunas, probably due to the large
      population size of yellowfin tuna. Since skipjack tuna appear to have even larger
      population sizes, it is not surprising that no genetic differentiation was
      detected between Atlantic and Pacific samples of these fish.

PMID- 15725350
TI  - Transitions in care during the end of life: changes experienced following
      enrolment in a comprehensive palliative care program.
AB  - BACKGROUND: Transitions in the location of care and in who provides such care can
      be extremely stressful for individuals facing death and for those close to them.
      The objective of this study was to describe the distribution of transitions in
      care experienced by palliative care patients following admission to a
      comprehensive palliative care program (PCP). A better understanding of these
      transitions may aid in reducing unnecessary change, help predict care needs,
      enhance transitions that improve quality of life, guide health care system
      communication links and maximize the cost-effective utilization of different care
      settings and providers. METHODS: Transition and demographic information
      pertaining to all patients registered in the PCP at the Queen Elizabeth II Health
      Sciences Centre (QEII), Halifax, Nova Scotia, Canada between January 1, 1998 and
      December 31, 2002 and who died on or prior to December 31, 2002 was extracted
      from the PCP database and examined. A transition was defined as either: (1) a
      change in location of where the patient was cared for by the PCP or, (2) a change
      in which clinical service provided care. Descriptive analysis provided
      frequencies and locations of transitions experienced from time of PCP admission
      to death and during the final two and four weeks of life, an examination of
      patient movement and a summary of the length of stay spent by patients at each
      care location. RESULTS: Over the five year period, 3974 adults admitted to the
      QEII PCP experienced a total of 5903 transitions (Mean 1.5; standard deviation
      1.8; median 1). Patients with no transitions (28%) differed significantly from
      those who had experienced at least one transition with respect to survival time,
      age, location of death and diagnosis (p < 0.0001). The majority of patients were
      admitted to the PCP from various acute care units (66%). Although 54% of all
      transitions were made to the home, only 60% of these moves included care provided
      by PCP staff. During the last four weeks of life, 47% of patients experienced at
      least one transition; 36% during the final two weeks of life. Shorter stays in
      each location were evident when care was actively provided by the PCP.
      CONCLUSION: A relatively small number of patients under the care of the PCP at
      the end of life, made several transitions in care setting or service provider.
      These particular patients need closer scrutiny to understand why such transitions
      take place so that clinical programs may be designed or modified to minimize the
      transitions themselves or the impact transitions have on patients and families.

PMID- 15725351
TI  - CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis.
AB  - BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease
      caused by repeated inhalations of finely dispersed organic particles or low
      molecular weight chemicals. The disease is characterized by an alveolitis
      sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever
      antigenic exposition continues, fibrosis. Although it is known that T-cell
      migration into the lungs is crucial in HP reaction, mechanisms implicated in this
      process remain undefined. METHODS: Using flow cytometry, immunohistochemistry,
      confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10
      and its receptor CXCR3 regulate the trafficking of CD8(+) T cells in HP lung.
      RESULTS: Our data demonstrated that lymphocytes infiltrating lung biopsies are
      CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the
      BAL of HP were CXCR3(+)/IFNgamma(+) Tc1 cells exhibiting a strong in vitro
      migratory capability in response to CXCL10. Alveolar macrophages expressed and
      secreted, in response to IFN-gamma, definite levels of CXCL10 capable of inducing
      chemotaxis of the CXCR3(+) T-cell line. Interestingly, striking levels of CXCR3
      ligands could be demonstrated in the fluid component of the BAL in individuals
      with HP. CONCLUSION: These data indicate that IFN-gamma mediates the recruitment
      of lymphocytes into the lung via production of the chemokine CXCL10, resulting in
      Tc1-cell alveolitis and granuloma formation.

PMID- 15725352
TI  - Analysis of the human Alu Ye lineage.
AB  - BACKGROUND: Alu elements are short (approximately 300 bp) interspersed elements
      that amplify in primate genomes through a process termed retroposition. The
      expansion of these elements has had a significant impact on the structure and
      function of primate genomes. Approximately 10 % of the mass of the human genome
      is comprised of Alu elements, making them the most abundant short interspersed
      element (SINE) in our genome. The majority of Alu amplification occurred early in
      primate evolution, and the current rate of Alu retroposition is at least 100 fold
      slower than the peak of amplification that occurred 30-50 million years ago. Alu
      elements are therefore a rich source of inter- and intra-species primate genomic
      variation. RESULTS: A total of 153 Alu elements from the Ye subfamily were
      extracted from the draft sequence of the human genome. Analysis of these elements
      resulted in the discovery of two new Alu subfamilies, Ye4 and Ye6, complementing
      the previously described Ye5 subfamily. DNA sequence analysis of each of the Alu
      Ye subfamilies yielded average age estimates of approximately 14, approximately
      13 and approximately 9.5 million years old for the Alu Ye4, Ye5 and Ye6
      subfamilies, respectively. In addition, 120 Alu Ye4, Ye5 and Ye6 loci were
      screened using polymerase chain reaction (PCR) assays to determine their
      phylogenetic origin and levels of human genomic diversity. CONCLUSION: The Alu Ye
      lineage appears to have started amplifying relatively early in primate evolution
      and continued propagating at a low level as many of its members are found in a
      variety of hominoid (humans, greater and lesser ape) genomes. Detailed sequence
      analysis of several Alu pre-integration sites indicated that multiple types of
      events had occurred, including gene conversions, near-parallel independent
      insertions of different Alu elements and Alu-mediated genomic deletions. A
      potential hotspot for Alu insertion in the Fer1L3 gene on chromosome 10 was also
      identified.

PMID- 15725354
TI  - Jacov Tal (1940 - 2005): remembrances of a friend.
AB  - An obituary commemorates the life and works of Jacov Tal.

PMID- 15725355
TI  - Recombinant Tula hantavirus shows reduced fitness but is able to survive in the
      presence of a parental virus: analysis of consecutive passages in a cell culture.
AB  - Tula hantavirus carrying recombinant S RNA segment (recTULV) grew in a cell
      culture to the same titers as the original cell adapted variant but presented no
      real match to the parental virus. Our data showed that the lower competitiveness
      of recTULV could not be increased by pre-passaging in the cell culture.
      Nevertheless, the recombinant virus was able to survive in the presence of the
      parental virus during five consecutive passages. The observed survival time seems
      to be sufficient for transmission of newly formed recombinant hantaviruses in
      nature.

PMID- 15725356
TI  - Ageing and the immune system in vivo: commentary on the 16th session of British
      Society for Immunology Annual Congress, Harrogate, December 2004.
AB  - The problems associated with the ageing immune system coupled with possible
      solutions were discussed recently at the British Society for Immunology Annual
      Congress in Harrogate in December 2004. The session "Ageing and the Immune System
      in vivo" dealt in details with the immune risk phenotype and the potential
      methods of reversing the problems of an ageing immune system. This is a
      commentary on that session.

PMID- 15725353
TI  - The Vpr protein from HIV-1: distinct roles along the viral life cycle.
AB  - The genomes of human and simian immunodeficiency viruses (HIV and SIV) encode the
      gag, pol and env genes and contain at least six supplementary open reading frames
      termed tat, rev, nef, vif, vpr, vpx and vpu. While the tat and rev genes encode
      regulatory proteins absolutely required for virus replication, nef, vif, vpr, vpx
      and vpu encode for small proteins referred to "auxiliary" (or "accessory"), since
      their expression is usually dispensable for virus growth in many in vitro
      systems. However, these auxiliary proteins are essential for viral replication
      and pathogenesis in vivo. The two vpr- and vpx-related genes are found only in
      members of the HIV-2/SIVsm/SIVmac group, whereas primate lentiviruses from other
      lineages (HIV-1, SIVcpz, SIVagm, SIVmnd and SIVsyk) contain a single vpr gene. In
      this review, we will mainly focus on vpr from HIV-1 and discuss the most recent
      developments in our understanding of Vpr functions and its role during the virus
      replication cycle.

PMID- 15725357
TI  - Two-part permutation tests for DNA methylation and microarray data.
AB  - BACKGROUND: One important application of microarray experiments is to identify
      differentially expressed genes. Often, small and negative expression levels were
      clipped-off to be equal to an arbitrarily chosen cutoff value before a
      statistical test is carried out. Then, there are two types of data: truncated
      values and original observations. The truncated values are not just another point
      on the continuum of possible values and, therefore, it is appropriate to combine
      two statistical tests in a two-part model rather than using standard statistical
      methods. A similar situation occurs when DNA methylation data are investigated.
      In that case, there are null values (undetectable methylation) and observed
      positive values. For these data, we propose a two-part permutation test. RESULTS:
      The proposed permutation test leads to smaller p-values in comparison to the
      original two-part test. We found this for both DNA methylation data and
      microarray data. With a simulation study we confirmed this result and could show
      that the two-part permutation test is, on average, more powerful. The new test
      also reduces, without any loss of power, to a standard test when there are no
      null or truncated values. CONCLUSION: The two-part permutation test can be used
      in routine analyses since it reduces to a standard test when there are positive
      values only. Further advantages of the new test are that it opens the possibility
      to use other test statistics to construct the two-part test and that it avoids
      the use of any asymptotic distribution. The latter advantage is particularly
      important for the analysis of microarrays since sample sizes are usually small.

PMID- 15725359
TI  - Does angiotensin-1 converting enzyme genotype influence motor or cognitive
      development after pre-term birth?
AB  - ABSTRACT : BACKGROUND : Raised activity of the renin-angiotensin system (RAS) may
      both amplify inflammatory and free radical responses and decrease tissue
      metabolic efficiency and thus enhance cerebral injury in the preterm infant. The
      angiotensin-converting enzyme (ACE) DD genotype is associated with raised ACE and
      RAS activity as well as potentially adverse stimuli such as inflammation. The DD
      genotype has been associated with neurological impairments in the elderly, and
      thus may be also associated with poorer motor or cognitive development amongst
      children born preterm prematurely. METHODS : The association of DD genotype with
      developmental progress amongst 176 Caucasian children born at less than 33 weeks
      gestation (median birthweight 1475 g, range 645-2480 g; gestation 30 weeks, range
      22-32; 108 male) was examined at 2 and 5 1/2 years of age. Measured neuro
      cognitive outcomes were cranial ultrasound abnormalities, cerebral palsy,
      disability, Griffiths Developmental Quotient [DQ] at 2 yrs, and General Cognitive
      Ability [British Ability Scales-11] and motor performance [ABC Movement], both
      performed at 5 1/2 yrs. All outcomes were correlated with ACE genotype. RESULTS :
      The DD genotype was not associated with lower developmental quotients even after
      accounting for important social variables. CONCLUSION : These data do not support
      either a role for ACE in the development of cognitive or motor function in
      surviving infants born preterm or inhibition of ACE as a neuroprotective therapy.

PMID- 15725358
TI  - Parkin mutation dosage and the phenomenon of anticipation: a molecular genetic
      study of familial parkinsonism.
AB  - BACKGROUND: parkin mutations are a common cause of parkinsonism. Possessing two
      parkin mutations leads to early-onset parkinsonism, while having one mutation may
      predispose to late-onset disease. This dosage pattern suggests that some parkin
      families should exhibit intergenerational variation in age at onset resembling
      anticipation. A subset of familial PD exhibits anticipation, the cause of which
      is unknown. The aim of this study was to determine if anticipation was due to
      parkin mutation dosage. METHODS: We studied 19 kindreds that had early-onset
      parkinsonism in the offspring generation, late-onset parkinsonism in the parent
      generation, and > or = 20 years of anticipation. We also studied 28 early-onset
      parkinsonism cases without anticipation. Patients were diagnosed by neurologists
      at a movement disorder clinic. parkin analysis included sequencing and dosage
      analysis of all 12 exons. RESULTS: Only one of 19 cases had compound parkin
      mutations, but contrary to our postulate, the affected relative with late-onset
      parkinsonism did not have a parkin mutation. In effect, none of the anticipation
      cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism
      patients without anticipation had parkin mutations. CONCLUSION: Anticipation is
      not linked to parkin, and may signify a distinct disease entity.

PMID- 15725360
TI  - The role of the vomeronasal system in food preferences of the gray short-tailed
      opossum, Monodelphis domestica.
AB  - Although feeding deficits have been reported in snakes and lizards following
      vomeronasal system disruption, no deficit has been previously reported in a
      mammal. We tested gray short-tailed opossums with items from four different food
      categories prior to occluding access to the vomeronasal organ. Preoperatively,
      opossums preferred meat to fruit or vegetables. Following occlusion of the
      nasopalatine canal, but not after control treatment, opossums failed to
      demonstrate food preferences.

PMID- 15725361
TI  - The Bosnian version of the international self-report measure of posttraumatic
      stress disorder, the Posttraumatic Stress Diagnostic Scale, is reliable and valid
      in a variety of different adult samples affected by war.
AB  - BACKGROUND: The aim of the present study was to assess the internal consistency
      and discriminant and convergent validity of the Bosnian version of a self-report
      measure of posttraumatic stress disorder (PTSD), the Posttraumatic Stress
      Diagnostic Scale (PTDS). The PTDS yields both a PTSD diagnosis according to the
      Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) and a
      measure of symptom severity. METHODS: 812 people living in Sarajevo or in Banja
      Luka in Bosnia-Herzegovina, of whom the majority had experienced a high number of
      traumatic war events, were administered the PTDS and other measures of trauma
      related psychopathology. The psychometric properties of the instrument were
      assessed using Cronbach's alpha and principal components analysis, and its
      construct validity was assessed via Spearman correlation coefficients with the
      other instruments. RESULTS: The PTDS and its subscales demonstrated high internal
      consistency. The principal components revealed by an exploratory analysis are
      broadly consistent with the DSM-IV subscales except that they reproduce some
      previously reported difficulties with the "numbing" items from the avoidance
      subscale. The construct validity of the PTDS was supported by appropriate
      correlations with other relevant measures of trauma related psychopathology.
      CONCLUSION: The Bosnian version of the PTDS thus appears to be a time-economic
      and psychometrically sound measure for screening and assessing current PTSD. This
      self-report measure awaits further validation by interview methods.

PMID- 15725363
TI  - p27Kip1 is expressed in proliferating cells in its form phosphorylated on
      threonine 187.
AB  - BACKGROUND: G1/S cell cycle progression requires p27Kip1 (p27) proteolysis, which
      is triggered by its phosphorylation on threonine (Thr) 187. Since its levels are
      abundant in quiescent and scarce in cycling cells, p27 is an approved marker for
      quiescent cells, extensively used in histopathology and cancer research. METHODS:
      However here we showed that by using a specific phosphorylation site (pThr187)
      antibody, p27 is detectable also in proliferative compartments of normal,
      dysplastic and neoplastic tissues. RESULTS: In fact, whereas un-phosphorylated
      p27 and MIB-1 showed a significant inverse correlation (Spearman R = -0.55; p <
      0,001), pThr187-p27 was positively and significantly correlated with MIB-1
      expression (Spearman R = 0.88; p < 0,001). Thus proliferating cells only stain
      for pThr187-p27, whereas they are un-reactive with the regular p27 antibodies.
      However increasing the sensitivity of the immunocytochemistry (ICH) by the use of
      an ultra sensitive detection system based on tiramide signal amplification,
      simultaneous expression and colocalisation of both forms of p27 was shown in
      proliferating compartments nuclei by double immunofluorescence and laser scanning
      confocal microscopy studies. CONCLUSION: Overall, our data suggest that p27
      expression also occurs in proliferating cells compartments and the combined use
      of both regular and phospho- p27 antibodies is suggested.

PMID- 15725362
TI  - The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma
      mansoni, and the distribution of related Pao-like elements.
AB  - BACKGROUND: Of the major families of long terminal repeat (LTR) retrotransposons,
      the Pao/BEL family is probably the least well studied. It is becoming apparent
      that numerous LTR retrotransposons and other mobile genetic elements have
      colonized the genome of the human blood fluke, Schistosoma mansoni. RESULTS: A
      proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome
      of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five
      discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes
      and EST databases indicated that members of this clade occurred in species of the
      Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but
      were absent from all plants, fungi and lower eukaryotes examined. Among the
      deuterostomes examined, only aquatic species harbored these types of elements.
      All four species of nematode examined were positive for Sinbad sequences,
      although among insect and vertebrate genomes, some were positive and some
      negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and
      was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed
      a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like
      elements, followed by the enzymatic domains of protease, reverse transcriptase
      (RT), RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT
      sequences from 26 elements revealed that Sinbad was most closely related to an
      unnamed element from the zebrafish Danio rerio and to Saci-1, also from S.
      mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of
      Drosophila simulans. Sinbad was only distantly related to the other schistosome
      LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are
      gypsy-like. Southern hybridization and bioinformatics analyses indicated that
      there were about 50 copies of Sinbad in the S. mansoni genome. The presence of
      ESTs representing transcripts of Sinbad in numerous developmental stages of S.
      mansoni along with the identical 5'- and 3'-LTR sequences suggests that Sinbad is
      an active retrotransposon. CONCLUSION: Sinbad is a Pao/BEL type retrotransposon
      from the genome of S. mansoni. The Pao/BEL group appears to be comprised of at
      least five discrete subfamilies, which tend to cluster with host species
      phylogeny. Pao/BEL type elements appear to have colonized only the genomes of the
      Animalia. The distribution of these elements in the Ecdysozoa, Deuterostomia, and
      Lophotrochozoa is discontinuous, suggesting horizontal transmission and/or
      efficient elimination of Pao-like mobile genetic elements from some genomes.

PMID- 15725365
TI  - [Outbreak of food-borne Norovirus associated with the consumption of sandwiches].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to conduct an investigation
      into an outbreak of food-borne disease at a hotel, when epidemiological and
      microbiological results determined that the etiological agent was Norovirus and
      the source of infection was food handlers. PATIENTS AND METHOD: We detected an
      outbreak of gastroenteritis in a group of 59 students and teachers from a
      secondary school who were staying at a hotel in Espot, Lleida (Spain). A historic
      cohort study was conducted into the consumption of water and food and clinical
      symptoms were also analyzed. We studied the water supply and various food items.
      Faecal specimens from 14 patients and four food handlers were cultured and
      examined for Norovirus by PCR-RT. The influence of each foodstuff was assessed by
      relative risk (RR) at 95% confidence intervals. RESULTS: We interviewed 96.6% of
      the patients (57/59). The overall attack rate was 66.7% (38/57). The median
      period of incubation was 25.0 hours (maxim 59 and minimum 19 hours). Symptoms
      included abdominal pain 94.7% (36/38), vomiting 86.8% (33/38), nausea 76.3%
      (29/38), diarrhoea 52.6% (20/38) and fever 48.6% (17/35). Of the four different
      kinds of drinking water and 13 food items studied, the only significant factor
      was the consumption of sandwiches (RR = 2.3; CI 95%, 1.1-5.1). Cultures were
      negative for bacteria. PCR-RT tests were positive for Norovirus in 12 of 14
      faecal samples. There were also positive results for the same virus in two of
      four faecal samples from food handlers, although neither of them presented
      clinical symptoms. CONCLUSIONS: This research highlights the fact that food
      handlers should always be investigated in the case of outbreaks of food borne
      Norovirus. They must strictly follow hygiene rules, especially when they produce
      food that is to be eaten without any form of cooking.

PMID- 15725366
TI  - [Sensitivity to change and minimally important difference of the Spanish version
      of the life-satisfaction questionnaire LISAT-8 in male patients with erectile
      dysfunction].
AB  - BACKGROUND AND OBJECTIVE: We determined the sensitivity to change and minimally
      important difference (MID) of the Spanish version of the life-satisfaction check
      list LISAT-8. PATIENTS AND METHOD: We included a random sample obtained from an
      open, naturalistic, prospective and multicenter study, which assessed the
      effectiveness of sildenafil as erectile dysfunction (ED) therapy. A total of 537
      patients, males older than 18 years, with ED and > active sexual desire, received
      flexible and at demand doses of sildenafil for 10 weeks. IIEF and LISAT-8
      questionnaires were used. MID was determined from the patient's classification
      according to change in erectile function domain of the IIEF after treatment as
      follows: no change (< 5 pts), small change (6 to 10 pts), moderate change (11 to
      15 pts) and big change (> 15 pts). RESULTS: Sildenafil significantly modified the
      baseline punctuation of the LISAT 8 from a crude value of 30.2 (5.9) pts (mean
      [standard deviation]), at baseline, to 34.7 (5.6) pts after treatment., and from
      55.4% (14.7%) to 66.8% (14.3%) in standardized punctuation (p < 0.0001 in both
      cases). Sildenafil responders showed a response increase of the total punctuation
      which was significantly higher than non-responders: 12.5% versus 4.3% (p <
      0.001). MID was 3.2 pts as crude punctuation, and 8.1% in normalized score.
      Statistically significant correlations were found between changes in LISAT-8 and
      changes in IIEF. CONCLUSIONS: The Spanish version of the LISAT-8 showed to be
      responsive to change in male ED patients. Meaningful MID was 3.1 pts (crude) and
      8.1% (normalized).

PMID- 15725367
TI  - [Arterial oxygen saturation at high altitude. A study on unacclimatised
      mountaineers and mountain dwellers].
AB  - BACKGROUND AND OBJECTIVE: We decided to determine how arterial oxygen saturation
      (SaO2) diminishes with altitude in unacclimatized mountaineers and in mountain
      dwellers. SUBJECTS AND METHOD: Pulseoximetric measurements in unacclimatized
      mountaineers (214 measurements in several Spanish mountains and in the Alps up to
      4,164 m) and in mountain dwellers (209 measurements in several Spanish and
      Bolivian villages up to 4,230 m). We performed pulseoximetric measurements for
      three consecutive days in eight mountaineers on the summit of Aneto (3,404 m) to
      ascertain whether SaO2 increases or not during early acclimatization. RESULTS:
      Equations describing the SaO2 reduction with altitude are as follows: a) for
      unacclimatized mountaineers, SaO2 = 98.8183 - 0.0001.h - 0.000001.h2, b) for
      mountain dwellers, SaO2 = 98.2171 + 0.0012.h - 0.0000008.h2. (SaO2 in %; h:
      altitude in m. Lower limit of 95% confidence intervals given in the text). SaO2
      of mountain dwellers is higher than that of unacclimatized mountaineers studied
      at the same altitude (p < 0.05 for any altitude over 1,692 m). SaO2 of
      mountaineers increased during early acclimatization (p < 0.05) to reach in few
      days the SaO2 of mountain dwellers. Unacclimatized mountaineers who spent the
      previous night over 2,000 m had higher SaO2 in altitude than those who slept
      under 2,000 m (p < 0.05). Mountaineers who performed any high-mountain activity
      (i.e. over 2,500 m) in the previous 12 months had higher SaO2 on the summit of
      Aneto than those who have never been over 2,500 m before (p < 0.05). CONCLUSION:
      SaO2 increases during the acclimatization process. Our equations serve to
      calculate the SaO2 which can be considered normal for healthy people for every
      altitude below 4,200 m, both before and after the acclimatization process.

PMID- 15725368
TI  - [Arterial oxygen and altitude].

PMID- 15725369
TI  - [Age and sexual function in males].

PMID- 15725370
TI  - [Early cancer diagnosis through proteomics of serum: fiction or fact?].

PMID- 15725372
TI  - [Prevalence of obesity in the Spanish adult population: 14 years of continuous
      increase].

PMID- 15725371
TI  - [Erythropoietin and cancer-related anaemia. Light and shade].
AB  - The use of recombinant human erythropoietin (r-HuEPO) in cancer patients improves
      hemoglobin levels and quality of life. This fact, already well known, made
      oncologists expect a positive outcome in radio and chemotherapy results, as well
      as in survival. However, new clinical trials show a preliminary evidence of
      impaired, instead of improved, survival when these agents are prescribed.
      Erythropoietin (EPO) is becoming a more complex hormone than it was expected. Its
      non-erythropoietic effects include, among others, angiogenesis and proliferation
      of certain types of cancer cells. In this work, we review erythropoietin as a
      natural hormone, as well as the different types of r-HuEPO, focusing on the
      confusing situation with regard to their use in oncology. We conclude that
      extreme care must be taken when EPO is prescribed to cancer patients, and we
      suggest to limit its use to symptomatic anemia, just to achieve moderate
      hemoglobin levels.

PMID- 15725373
TI  - [Hepatitis B virus in Catalan adopted or immigrant children].

PMID- 15725374
TI  - [Clinical functional results of surgery on large pulmonary bullae].

PMID- 15725375
TI  - [Fixed drug eruption associated to loperamide].

PMID- 15725376
TI  - [Hyponatremia, cerebral edema and brain death in a MDMA acute intoxication].

PMID- 15725377
TI  - [Sentinel lymph node biopsy for transit recurrent melanoma].

PMID- 15725379
TI  - Genetic population structure of the lionfish Pterois miles (Scorpaenidae,
      Pteroinae) in the Gulf of Aqaba and northern Red Sea.
AB  - The aim of this study is to reveal gene flow between populations of the coral
      reef dwelling lionfish Pterois miles in the Gulf of Aqaba and northern Red Sea.
      Due to the fjord-like hydrography and topology of the Gulf of Aqaba, isolation of
      populations might be possible. Analysis of 5' mitochondrial control region
      sequences from 94 P. miles specimens detected 32 polymorphic sites, yielding 38
      haplotypes. Sequence divergence among different haplotypes ranged from 0.6% to
      9.9% and genetic diversity was high (h=0.85, pi=1.9%). AMOVA indicates panmixia
      between the Gulf of Aqaba and northern Red Sea, but analysis of migration pattern
      shows an almost unidirectional migration originating from the Red Sea.

PMID- 15725378
TI  - Forcing reversibility in the no-strand-bias substitution model allows for the
      theoretical and practical identifiability of its 5 parameters from pairwise DNA
      sequence comparisons.
AB  - Because of the base pairing rules in DNA, some mutations experienced by a portion
      of DNA during its evolution result in the same substitution, as we can only
      observe differences in coupled nucleotides. Then, in the absence of a bias
      between the two DNA strands, a model with at most 6 different parameters instead
      of 12 is sufficient to study the evolutionary relationship between homologous
      sequences derived from a common ancestor. On the other hand the same symmetry
      reduces the number of independent observations which can be made. Such a
      reduction can in some cases invalidate the calculation of the parameters. A
      compromise between biologically acceptable hypotheses and tractability is
      introduced and a five-parameter reversible no-strand-bias condition (RNSB) is
      presented. The identifiability of the parameters under this model is shown by
      examples.

PMID- 15725380
TI  - Evolution of transcription factor DNA binding sites.
AB  - In bioinformatics, binding of transcription regulatory factors to the cognate
      binding sites is usually described by sequence-specific binding energy, which is
      estimated from a training sample of sites. This model implies that all binding
      sites with binding energy above some threshold are functional and site sequence
      variations should be considered neutral until they do not reduce this energy
      below the threshold. To quantify this energy, the binding profile (positional
      weight matrix, PWM) model or consensus-based model is usually applied. Here we
      show that in many cases available data are not sufficient to construct a relevant
      PWM, and modified consensus-based model could be more effective to describe
      binding properties. Further, using the data about binding sites of several
      transcription factors, we demonstrate that some non-consensus nucleotides in
      "orthologous sites" (that is, binding sites of the same factor upstream of
      orthologous genes), which have been believed to be irrelevant or even hindering
      the regulation, are evolutionary very stable and specific for the regulated gene.
      For each two considered genomes, the number of substitutions between non
      consensus nucleotides is far less than the expected number of neutral
      substitutions. Moreover, in several positions of binding sites regulating
      different genes, there are non-consensus nucleotides conserved in distant
      genomes. It means that there exists a selection pressure, which results in the
      stability of non-consensus nucleotides.

PMID- 15725381
TI  - Trypanosoma cruzi-infected individuals demonstrate varied antibody responses to a
      panel of trans-sialidase proteins encoded by SA85-1 genes.
AB  - Chronic infection with Trypanosoma cruzi causes significant morbidity and
      mortality. The parasite expresses on its surface and sheds into the extracellular
      milieu a large superfamily of trans-sialidase proteins. Previous studies have
      demonstrated that during T. cruzi infection, the trans-sialidase superfamily
      stimulates an antibody response, but how individuals respond to different
      proteins of the trans-sialidase superfamily remain poorly defined. In this
      report, we present an analysis of the antibody response of chronically infected
      individuals and inbred strains of mice to a panel of 11 different trans-sialidase
      proteins encoded by surface antigen 85 kD (SA85-1) genes. These data indicate
      that: (1) 90% of the individuals tested generated antibodies to one or more trans
      sialidase proteins; (2) the individuals develop different patterns of antibody
      responsiveness to the panel of trans-sialidase proteins; (3) three inbred strains
      of mice develop trans-sialidase antibody responses, but each strain develops a
      different pattern of antibody response to the panel of trans-sialidase proteins;
      (4) the differences in the pattern of antibody response by the mouse strains are
      independent of MHC differences; and (5) trans-sialidase proteins that do not
      stimulate an antibody response during T. cruzi infection can stimulate a response
      following immunization. Together these data indicate that during T. cruzi
      infection individuals develop a diverse trans-sialidase antibody response that
      appears to be affected by genetic and environmental factors.

PMID- 15725382
TI  - Pharmacodynamic interactions of amodiaquine and its major metabolite
      desethylamodiaquine with artemisinin, quinine and atovaquone in Plasmodium
      falciparum in vitro.
AB  - The antimalarial in vitro activities of amodiaquine and desethylamodiaquine in
      combination with atovaquone, quinine and artemisinin against Plasmodium
      falciparum were investigated in strains F-32, FCR-3 and K-1. These parasitic
      strains have different sensitivity profiles to the standard antimalarial
      chloroquine, but all can be considered sensitive to the test drugs, representing
      the recommended situation for introduction of two partner drugs in combination
      therapy. Amodiaquine showed marked synergism when combined with each of the three
      partner compounds at concentration ratios between 90 and 9x10(-7), including the
      therapeutically relevant range. The interaction profiles of desethylamodiaquine
      with quinine and artemisinin also showed predominantly synergism over a wide
      range of concentration ratios between 70 and 9x10(-7). The responses to all
      combinations exhibited signs of strain-specificity, but such phenomena were
      usually observed outside the therapeutic range of the concentration ratios.
      Synergism was generally more marked with increasing EC values, i.e. at
      concentrations expected to be therapeutically effective and thus clinically
      relevant. Even trace quantities of amodiaquine were able to potentiate the
      activity of structurally unrelated antimalarial drugs.

PMID- 15725383
TI  - Impaired recognition by Toll-like receptor 4 is responsible for exacerbated
      murine Pneumocystis pneumonia.
AB  - We investigated the effect of Toll-like receptor 4 (TLR4) on the progression of
      murine Pneumocystis pneumonia. TLR4-mutant C3H/HeJ and wild-type C3H/HeN mice
      were infected with Pneumocystis after depletion of CD4 T cells. Mutant mice lost
      body weight more quickly and showed exacerbated pulmonary injury even though
      there was no difference in Pneumocystis organism burden in the lung. Mutant mice
      showed reduced levels of IL-10, IL-12p40 and MIP-2 accompanied by elevated levels
      of TNF-alpha and IL-6 in the bronchoalveolar lavage fluid compared with those of
      wild-type mice 8 weeks after the infection. In response to stimulation with
      Pneumocystis antigen, the production of IL-10, IL-12p40 and MIP-2 by alveolar
      macrophages was partially impaired in mutant mice, while that in wild-type mice
      was suppressed by the anti-TLR4/MD-2 mAb, MTS510. Unlike the response to
      lipopolysaccharide stimulation, TLR4-reconstituted HEK293 cells showed no
      elevated NF-kappaB activation after stimulation with Pneumocystis antigen. Taken
      together, these findings suggest that recognition of Pneumocystis by TLR4 helps
      to regulate the host inflammatory responses through cytokine and chemokine
      production by alveolar macrophages.

PMID- 15725384
TI  - Relative activity of the feline immunodeficiency virus promoter in feline and
      primate cell lines.
AB  - The feline immunodeficiency virus (FIV) long terminal repeat (LTR), compared with
      some primate lentiviral LTRs, is quite a strong basal promoter. However, it seems
      to be highly species-specific in function and generally not very efficient in
      cells of non-feline origin. This study systematically explored the function of
      the FIV LTR in simian Cos cells compared with its activity in feline and human
      cells. Our studies, using biologically relevant two- and three-plasmid trans
      complementation assays followed by semi-quantitative reverse transcriptase PCR,
      show that the FIV LTR is functional in Cos cells. The results of the Cos
      experiment are different from previously reported literature and suggest that the
      strain specificity of the FIV LTR is an important determinant of whether the LTR
      will be functional in a particular cell type.

PMID- 15725385
TI  - Human T cell epitope mapping of the Schistosoma mansoni 14-kDa fatty acid-binding
      protein using cells from patients living in areas endemic for schistosomiasis.
AB  - The development of a defined anti-schistosomiasis vaccine would contribute to the
      current control strategy mainly because immunization provides long-lasting
      immunity to the disease. Sm14, one of the six Schistosoma mansoni antigens
      selected by WHO as a candidate to compose a subunit vaccine against
      schistosomiasis, has been associated with resistance to S. mansoni infection in
      human beings and is able to induce protection in the murine model. To identify
      human T cell epitopes in Sm14, we used the TEPITOPE algorithm to select peptides
      that would most likely bind to several HLA-DR molecules. In this study, three
      Sm14 epitopes were selected and produced as synthetic peptides. Human T cell
      responses from schistosomiasis patients living in endemic areas in Brazil were
      determined by proliferation assay and IL-5 and IFN-gamma measurements.
      Differential peptide recognition and cytokine production in response to Sm14
      epitopes were observed in individuals resistant to S. mansoni infection versus
      susceptible individuals. Sm14(32-48) and Sm14(53-69) peptides were preferentially
      recognized by peripheral blood mononuclear cells (PBMCs) of S. mansoni-resistant
      individuals, and Sm14(53-69) induced significant production of IFN-gamma.
      Additionally, Sm14(32-48) and Sm14(53-69) were "promiscuous" peptides, since they
      were able to induce cellular immune responses in individuals carrying 10 and 8,
      respectively, of the 11 HLA-DR molecules expressed in the studied population.
      Among Sm14 synthetic peptides tested in this study, we identified Sm14(32-48) and
      Sm14(53-69) as promising candidates to compose an anti-schistosomiasis vaccine,
      since they seem to be related to resistance to human schistosomiasis.

PMID- 15725386
TI  - HIV-1-derived self-inactivating lentivirus vector induces megakaryocyte lineage
      specific gene expression.
AB  - Pluripotent, self-renewing, hematopoietic stem cells are considered good targets
      for gene modification to treat a wide variety of disorders. However, as many
      genes are expressed in a stage-specific manner during the course of hematopoietic
      development, it is necessary to establish a lineage-specific gene expression
      system to ensure the proper expression of transduced genes in hematopoietic stem
      cells. In this study, we constructed a VSV-G-pseudotyped, human immunodeficiency
      virus type 1-based, self-inactivating lentivirus vector that expressed green
      fluorescent protein (GFP) under the control of the human CD41 (glycoprotein 2b;
      GP2b) promoter; this activity is restricted to megakaryocytic lineage cells. The
      recombinant virus was used to infect human peripheral blood CD34+ (hematopoietic
      stem/progenitor) cells, and lineage-specific gene expression was monitored with
      GFP measurements. The analysis by FACS determined that GFP expression driven by
      the GP2b promoter was restricted to megakaryocytic progenitors and was not
      present in erythrocytes. Furthermore, in the hematopoietic colony-forming assay,
      GFP expression was restricted to colony-forming units-megakaryocyte (CFU-Meg)
      colonies under the control of the GP2b promoter, whereas all myeloid colonies
      (burst-forming units-erythroid, colony-forming units-granulocyte-macrophage, and
      CFU-Meg) expressed GFP when the transgene was regulated by the cytomegalovirus
      promoter. These results demonstrated lineage-specific expression after gene
      transduction of hematopoietic stem cells. The application of this vector system
      should provide a useful tool for gene therapy to treat disorders associated with
      megakaryocyte (platelet) dysfunction.

PMID- 15725387
TI  - Macrophages at intermediate stage of maturation produce high levels of IL-12 p40
      upon stimulation with Leishmania.
AB  - IL-12 is one of the main cytokines driving the immune response to a resistant
      phenotype in leishmaniasis and in several other diseases involving intracellular
      microbes. In this study, we investigated IL-12 production by mononuclear
      phagocytes at several developmental stages when stimulated with Leishmania major,
      L. amazonensis or L. chagasi. Bone marrow cells were cultured for 4-6 days in
      vitro in the presence of M-CSF, GM-CSF or IL-3. After density separation, only
      cells banding at the 40-50% Percoll interface, but not those at 20-40% or 50-80%
      interfaces, produced large amounts of IL-12 p40 when stimulated with LPS or live
      Leishmania promastigotes. However, only low levels of IL-12 p70 were produced
      under these conditions. The high IL-12 p40-producing cells could be similarly
      derived from mouse strains with different susceptibility to Leishmania.
      Quantitative analysis of monocyte/macrophage lineage marker expression, in
      combination with positive and negative selection, led to the conclusion that the
      high IL-12 p40-producing cells are macrophages at an intermediate stage of
      maturation between immature and fully differentiated cells, expressing ER-HR3 but
      only low levels of the mature markers, scavenger receptor and CD11b/Mac-1. They
      do not express any of the precursor markers CD31/ER-MP12, Ly-6C/ER-MP20 or ER
      MP58. Because recruitment of monocytes to an infection site and its draining
      lymph node is a general phenomenon, the notion that, developing from these
      monocytes, a population of mononuclear phagocytes at an intermediate maturation
      stage has the capacity to synthesize large amounts of IL-12 p40 has significant
      bearing on our understanding of immune regulation in leishmaniasis and also in
      infections by other pathogens.

PMID- 15725388
TI  - Prevention of hospital infection.
AB  - The prevention of nosocomial infections is an important aspect of patient care,
      particularly in high-risk areas such as intensive care units (ICUs). Local
      hospital leadership needs to develop easily defined infection-control policies
      that are evidence-based. These infection-control policies also require the
      presence of a dedicated group of infection-control practitioners to provide
      education, collect surveillance data, and oversee the implementation of the local
      infection-control plan.

PMID- 15725389
TI  - Post-ictal circulating levels of allopregnanolone in children with partial or
      generalized seizures.
AB  - INTRODUCTION: Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) is a
      neurosteroid with a potent modulating activity on the gamma-aminobutyric acid
      (GABA)(a) receptor complex. It plays a key role in the epileptogenesis of partial
      seizures. Serum allopregnanolone concentrations significantly increase in the
      postcritical phase. In the present study we investigated the post-ictal serum
      allopregnanolone levels in children with partial seizures and generalized
      seizures, respectively. PATIENTS AND METHODS: Three groups of subjects were
      included in the study. Group 1 consisted of 18 children affected by complex
      partial seizures. Group 2 consisted of 11 children presenting with generalized
      epilepsy. Group 3 consisted of 20 healthy age-matched subjects. Serum
      allopregnanolone levels were assayed in the inter-ictal phase and within 30 min
      after an epileptic event. RESULTS: The data we obtained suggest that circulating
      allopregnanolone level significantly increases in the post-ictal phase. However,
      we found no significant differences in the post-ictal serum allopregnanolone
      concentrations between patients with partial seizures and those with generalized
      seizures. CONCLUSIONS: Further studies are needed to establish if
      allopregnanolone is a reliable circulating marker of epileptic seizures. However,
      our observations seem to indicate that post-ictal circulating allopregnanolone
      level is not useful in differentiating focal and generalized epilepsy events.

PMID- 15725391
TI  - Topological properties of the energy landscape of small peptides.
AB  - In several works it has been shown that the interplay between short range and
      long range interactions, mimicking the hydrophobic effect, leads to the formation
      of the typical secondary structures in proteins, alpha-helices and beta-sheets.
      In this work we study in detail how the general properties of the energy
      landscape emerge in a model that presents both components. In this regard it
      proves useful a sort of perturbative approach. In our model many features of the
      energy landscape in absence of long range interaction can be determined
      analytically. The comparison between the energy landscape of this reduced model
      to that of the complete model gives interesting insight on the role of long range
      interactions.

PMID- 15725390
TI  - Protein evolution in viral quasispecies under selective pressure: a thermodynamic
      and phylogenetic analysis.
AB  - The evolution of RNA viruses under antiviral pressure is characterized by high
      mutation rates and strong selective forces that induce extremely rapid changes of
      protein sequences. This makes the course of molecular evolution directly
      observable on time scales of months. Here we study the interplay between
      selection for drug resistance and selection for thermodynamic stability in the
      protease (PR) and the reverse transcriptase (RT) of human immunodeficiency virus
      type 1 (HIV-1) clones extracted from two patients with complex treatment
      histories. This analysis shows that folding thermodynamic properties may
      fluctuate very strongly in the course of quasispecies evolution under selective
      pressure. For the first case, our data suggest that folding efficiency of the RT
      is sacrificed at the advantage of drug resistance, while the corresponding PR
      seems to undergo selection for thermodynamic stability in the absence of
      substitutions associated to resistance. The PR of the second case is not
      submitted to antiviral pressure during the period analyzed and seems to initiate
      random fluctuations that lead to the accidental increase of its folding
      efficiency. In summary, joint consideration of sequence evolution and
      thermodynamic parameters can represent a more comprehensive approach for the
      study of the evolution of RNA viruses.

PMID- 15725392
TI  - Biologically active bisquaternary ammonium chlorides: physico-chemical properties
      of long chain amphiphiles and their evaluation as non-viral vectors for gene
      delivery.
AB  - The biological properties of bisquaternary ammonium salts, which are derivatives
      of N,N-bisdimethyl-1,2-ethanediamine (bis-C(n)BEC), of general formula
      /C(n)H(2n+1)OOCCH2(CH3)2N(+)CH2CH2N(+)(CH3)2CH2COOC(n)H(2n+1)/2Cl-, were
      investigated (n=10, 12, 14). The interaction with model membrane was studied by
      differential scanning calorimetry experiments, and the apparent adiabatic molar
      compressibility of their solution as a function of concentration was obtained by
      sound velocity measurements. Their biological activities were assayed by
      Electrophoresis Mobility Shift, MTT proliferation, and transient transfection.
      All the investigated compounds interact with the DNA and are able to transfect
      DNA, when they are co-formulated with DOPE, with an efficiency significantly
      greater than that of a standard commercial transfection reagent. Bis-C(14)BEC is
      the only molecule able to deliver DNA inside the cells without a helper lipid, as
      shown by EGFP expression, albeit with a low efficiency in comparison with a
      standard commercial transfection reagent. This may be due to a slightly different
      interaction of bis-C14BEC from bis-C10BEC and bis-C12BEC with phospholipid
      bilayers. Bis-C10BEC and bis-C12BEC show a slight fluidizing effect, while bis
      C14BEC increases stability of both the gel and the rippled gel phases.

PMID- 15725393
TI  - Supportive evidence for an allelic association of the human KCNJ10 potassium
      channel gene with idiopathic generalized epilepsy.
AB  - PURPOSE: Quantitative trait loci (QTL) mapping in mice revealed a seizure-related
      QTL (Szs1), for which the inward-rectifying potassium channel Kcnj10 is the most
      compelling candidate gene. Association analysis of the human KCNJ10 gene
      identified a common KCNJ10 missense variation (Arg271Cys) that influences
      susceptibility to focal and generalized epilepsies. The present replication study
      tested the initial finding that the KCNJ10 Cys271 allele is associated with
      seizure resistance to common syndromes of idiopathic generalized epilepsy (IGE).
      METHODS: The study sample comprised 563 German IGE patients and 660 healthy
      population controls. To search for seizure type-specific effects, two IGE
      subgroups were formed, comprising 258 IGE patients with typical absences (IAE
      group) and 218 patients with juvenile myoclonic epilepsy (JME group). A TaqMan
      nuclease assay was used to genotype the KCNJ10 single nucleotide polymorphism
      c.1037C > T (dbSNP: rs1130183) that alters amino acid at position 271 from
      arginine to cysteine. RESULTS: Replication analysis revealed a significant
      decrease of the Cys271 allele frequency in 446 IGE patients compared to controls
      (chi2 = 3.52, d.f. = 1, P = 0.030, one-sided; OR(Cys271+) = 0.69; 95% CI: 0.50
      0.95). Among the IGE subgroups, lack of the Cys271 allele was accentuated in the
      JME group (chi2 = 5.20, d.f. = 1, P = 0.011, one-sided). CONCLUSION: Our results
      support previous evidence that the common KCNJ10 Arg271Cys missense variation
      influences seizure susceptibility of common IGE syndromes.

PMID- 15725394
TI  - Expression of the standard scorpion alpha-toxin AaH II and AaH II mutants leading
      to the identification of some key bioactive elements.
AB  - The AaH II toxin from the scorpion Androctonus australis Hector is considered to
      be the standard alpha-toxin because it selectively binds with the highest known
      affinity to site 3 of mammalian voltage-activated Na+ channels (Na(v)) on rat
      brain synaptosomes but does not bind to insect synaptosomes. We generated two
      different constructs in pMALp allowing us to produce AaH II fused with the
      maltose-binding protein (MBP) in E. coli. We obtained reasonable amounts of
      recombinant AaH II after cleavage by enterokinase at the site DDDDK. We show that
      the introduction of a net negative charge at the C-terminus by the suppression of
      H64 amidation and the addition of an extra residue to the C-terminus (G65) led to
      fully active AaH II mutants, exhibiting exactly the same affinity as the native
      toxin for its target on rat brain synaptosomes. In contrast, the mutation of
      residue K58 into V, I or E residues drastically reduced toxin activity.

PMID- 15725395
TI  - Co-culture of neurones with glutathione deficient astrocytes leads to increased
      neuronal susceptibility to nitric oxide and increased glutamate-cysteine ligase
      activity.
AB  - The antioxidant glutathione (GSH) plays an important role in protecting the
      mitochondrial electron transport chain (ETC) from damage by oxidative stress in
      astrocytes and neurones. Neurones co-cultured with astrocytes have greater GSH
      levels, compared to neurones cultured alone, leading to the hypothesis that
      astrocytes play a key role in brain GSH metabolism by supplying essential GSH
      precursors to neurones. A previous study has postulated that damage to the ETC
      following exposure to reactive nitrogen species (RNS) is less in co-cultured
      neurones, compared to neurones cultured alone, because of the greater GSH levels
      in the former cells. To investigate this further, primary culture rat neurones
      were co-cultured with either rat astrocytes activated with IFN-gamma and LPS to
      produce NO, or NO-generating astrocytes that had been depleted of intracellular
      GSH by 87% following incubation with the GSH synthesis inhibitor L-buthionine-S,R
      sulfoximine (L-BSO). Neurones incubated with NO-generating astrocytes depleted of
      GSH were unable to elevate GSH levels, unlike neurones co-cultured with NO
      generating astrocytes. Complexes II + III and IV of the neuronal ETC were
      significantly inhibited following exposure to NO-generating astrocytes depleted
      of GSH. No ETC damage was observed in neurones co-cultured with NO-generating
      astrocytes. Although neurones co-cultured with GSH depleted astrocytes did not
      increase cellular GSH levels, the activity of glutamate cysteine ligase (GCL),
      the rate-limiting enzyme of GSH synthesis, was increased by 218%, compared to
      neurones cultured with control astrocytes. This suggests that neuronal GCL
      activity could be modulated when GSH metabolism is inhibited in neighboring
      astrocytes.

PMID- 15725396
TI  - Characterization of cell proliferation in the adult dentate under normal
      conditions and after kainate induced seizures using ribonucleotide reductase and
      BrdU.
AB  - Ribonucleotide reductase (RNR), an enzyme for DNA synthesis, was recently used as
      a marker of proliferating cells in the dentate gyrus and subventricular zone in
      normal adult mammalian brains. However, the duration of RNR expression in normal
      adult brain and the expression pattern of RNR in the adult dentate gyrus
      following brain injury have not been explored. In this study, we examined the
      duration of the RNR expression in newborn cells in the normal adult rat brain by
      analysis of RNR and BrdU double-labeled specimens at different time intervals
      after BrdU application. Secondly, we induced, in adult rats, seizures by kainic
      acid and investigated the changes in expression of RNR following seizures, and
      characterized the phenotype of RNR-positive cells using a variety of other
      markers. Our results revealed that RNR was detectable in proliferating cells from
      2 h to at least 1 day. At 7 and 28 days after seizures, there was a fivefold
      increase in number of clusters of RNR-positive cells in the dentate gyrus, and a
      doubling of the number of BrdU-labeled cells in each cluster. Proliferating
      astrocytes and neuronal precursors were recognized in each RNR-positive cell
      cluster, and both types increased in number after seizures. Colocalization of RNR
      and activated caspase-3 was observed at 7 days, indicating that proliferating
      cells were susceptible to status epilepticus induced damage. RNR
      immunohistochemistry provides a useful approach in experiments investigating a
      change in cell proliferation, revealing the location, number, morphology and fate
      of newly formed cells after, e.g., brain injury.

PMID- 15725397
TI  - Inhibition of MG132-induced mitochondrial dysfunction and cell death in PC12
      cells by 3-morpholinosydnonimine.
AB  - The effect of 3-morpholinosydnonimine (SIN-1) against the cytotoxicity of MG132,
      a proteasome inhibitor, in differentiated PC12 cells was assessed by measuring
      the effect on the mitochondrial membrane permeability. Treatment of PC12 cells
      with MG132 resulted in the nuclear damage, decrease in the mitochondrial
      transmembrane potential, cytosolic accumulation of cytochrome c, activation of
      caspase-3, increase in the formation of reactive oxygen species (ROS), and
      depletion of GSH. Addition of SIN-1, a producer of nitric oxide (NO) and
      superoxide, differentially reduced the MG132-induced cell death and GSH depletion
      concentration dependently with a maximal inhibitory effect at 150 microM. Carboxy
      PTIO, superoxide dismutase, Mn-TBAP, and ascorbate prevented the inhibitory
      effect of SIN-1 on the cytotoxicity of MG132. SIN-1 inhibited the MG132-induced
      change in the mitochondrial membrane permeability, ROS formation and decrease in
      GSH contents in PC12 cells. S-nitroso-N-acetyl-DL-penicillamine reduced the MG132
      induced cell death in PC12 cells, whereas peroxynitrite and H2O2 did not affect
      the cytotoxicity of MG132. The results suggest that NO and superoxide liberated
      from SIN-1 exert an inhibitory effect against the cytotoxicity of MG132. SIN-1
      may inhibit the MG132-induced viability loss in PC12 cells by suppressing change
      in the mitochondrial membrane permeability that is associated with oxidative
      damage.

PMID- 15725398
TI  - The gas7 protein potentiates NGF-mediated differentiation of PC12 cells.
AB  - The growth-arrest-specific protein gas7 is required for morphological
      differentiation of cultured mouse cerebellar neurons and PC12 cells. Moreover,
      its overexpression in various cell types induces neurite-like outgrowth. The role
      of gas7 in neuronal differentiation was further characterized by adenovirus
      mediated overexpression in PC12 cells and quantification of the expression of
      various neuronal markers, in the absence and presence of different concentrations
      of nerve growth factor (NGF). The potential neuroprotective activity of gas7
      against various neurotoxic insults was also assessed. In addition to promoting
      the formation of neurite-like extensions, overexpression of gas7 potentiated NGF
      mediated neuronal differentiation of PC12 cells, as shown by the enhanced
      expression of the neuronal proteins betaIII-tubulin, synaptotagmin, alpha7
      subunit of the acetylcholine receptor, and dihydropyrimidinase related protein-3.
      This effect was exerted independently of cell cycle progression, as gas7 did not
      affect proliferation of PC12 cells. While some differentiation enhancers protect
      PC12 cells against lethal insults, gas7 overexpression in PC12 cells did not
      protect against oxygen-glucose deprivation, the calcium ionophore A23187, or the
      nitric oxide donor sodium nitroprusside, suggesting that gas7 is not
      neuroprotective. The ability of gas7 to potentiate neuronal differentiation makes
      it a potential therapeutic target to promote re-establishment of neuronal
      connections in the injured or diseased brain, such as following stroke.

PMID- 15725399
TI  - Tyrosine kinase A but not phosphacan/protein tyrosine phosphatase-zeta/beta
      immunoreactivity and protein level changes in neurons and astrocytes in the
      gerbil hippocampus proper after transient forebrain ischemia.
AB  - In the present study, ischemia-related changes in tyrosine kinase A (trkA) and
      phosphacan/protein tyrosine phosphatase-zeta/beta (PTP-zeta/beta)
      immunoreactivities and protein contents were examined in the hippocampus proper
      after transient forebrain ischemia for 5 min in a gerbil model. Our
      investigations showed that ischemia-induced changes occurred in trkA
      immunoreactivity in the hippocampal CA1 region, but not in the CA2/3 region of
      the hippocampus proper. In the sham-operated group, trkA immunoreactivity was
      barely detectable. trkA immunoreactivity increased from 30 min after ischemia and
      peaked at 12 h. Four days after ischemic insult, trkA immunoreactivity was
      observed in GFAP-immunoreactive astrocytes in the strata oriens and radiatum. In
      addition, we found that ischemia-related changes in trkA protein content were
      similar to immunohistochemical changes. On the other hand, PTP-zeta/beta
      immunoreactivities in the hippocampus proper were unaltered by forebrain
      ischemia. These results suggest that chronological changes of trkA after
      transient forebrain ischemia may be associated with an ischemic damage
      compensatory mechanism in CA1 pyramidal cells.

PMID- 15725400
TI  - Dye coupling among satellite glial cells in mammalian dorsal root ganglia.
AB  - Dorsal root ganglia (DRG) are key elements in sensory signaling under
      physiological and pathological conditions. Little is known about electrical
      coupling among cells in these ganglia. In this study, we injected the fluorescent
      dye Lucifer yellow (LY) into single cells to examine dye coupling in DRG. We
      found no dye coupling between neurons or between neurons and their attendant
      satellite glial cells (SGCs). In mouse DRG, we observed that in 26.2% of the
      cases SGCs that surround a given neuron were dye coupled. In only 3.2% of the
      cases SGCs that make envelopes around different neurons were coupled. The data
      from mouse ganglia were very similar to those from rat and guinea pig DRG. The
      results obtained by injection of the tracer biocytin were very similar to those
      observed with LY. The coupling incidence within the envelopes increased 3.1-fold
      by high extracellular pH (8.0), but coupling between envelopes was not affected.
      Acidic pH (6.8) reduced the coupling. High extracellular K+ (9.4 mM) increased
      the coupling 2.4-fold and 4.7-fold within and between envelopes, respectively.
      Low extracellular Ca2+ (0.5, 1.0 mM) partly reversed the effect of high K+ on
      coupling. The results showed that SGCs in mammalian sensory ganglia are connected
      by gap junctions. This coupling is very sensitive to changes in pH, and can
      therefore be modulated under various physiological and pathological conditions.
      The dependence of the coupling on extracellular K+ and Ca2+ suggests that the
      permeability of gap junctions can be altered by physiological and pharmacological
      stimuli.

PMID- 15725401
TI  - Suppression of potassium channels elicits calcium-dependent plateau potentials in
      suprachiasmatic neurons of the rat.
AB  - By using whole-cell recordings in acute and organotypic hypothalamic slices, we
      found that following K+ channel blockade, sustained plateau potentials can be
      elicited by current injection in suprachiasmatic neurons. In an attempt to
      determine the ionic basis of these potentials, ion-substitution experiments were
      carried out. It appeared that to generate plateau potentials, calcium influx was
      required. Plateau potentials were also present when extracellular calcium was
      replaced by barium, but were independent upon an increase in the intracellular
      free calcium concentration. Substitution of extracellular sodium by the
      impermeant cation N-methyl-D-glucamine indicated that sodium influx could also
      contribute to plateau potentials. To gain some information on the pharmacological
      profile of the Ca++ channels responsible for plateau potentials, selective
      blocker of various types of Ca++ channel were tested. Plateau potentials were
      unaffected by isradipine, an L-type Ca++ channel blocker. However, they were
      slightly reduced by omega-conotoxin GVIA and omega-agatoxin TK, blockers of N
      type and P/Q-type Ca++ channels, respectively. These data suggest that R-type
      Ca++ channels probably play a major role in the genesis of plateau potentials. We
      speculate that neurotransmitters/neuromodulators capable of reducing or
      suppressing potassium conductance(s) may elicit a Ca++-dependent plateau
      potential in suprachiasmatic neurons, thus promoting sustained firing activity
      and neuropeptide release.

PMID- 15725402
TI  - Strengthening of non-NMDA receptor-dependent horizontal pathways between primary
      and lateral secondary visual cortices after NMDA receptor-dependent oscillatory
      neural activities.
AB  - Emergence of oscillatory signal flows between the primary visual cortex (Oc1) and
      medial secondary visual cortex (Oc2M) was previously dynamically demonstrated in
      rat brain slices by us. Applying caffeine, a neural modulator, to the slices and
      using optical recording methods revealed this facilitation along horizontal
      intrinsic pathways in which initial forward propagation from Oc1 to Oc2M was
      dependent on both N-methyl-D-aspartate receptors (NMDARs) and non-NMDARs.
      Conversely, oscillatory backward propagation from Oc2M to Oc1 was entirely
      dependent on NMDARs. The present study examined: (1) whether the signal behavior
      between Oc1 and lateral secondary visual cortex (Oc2L) is based on the same
      mechanism with that between Oc1 and Oc2M; and (2) how non-NMDAR and NMDAR
      activities underlie opening of horizontal corticocortical pathways between Oc1
      and Oc2. Under NMDAR blockade, signals elicited in the Oc1 either could not or
      only weakly penetrated the Oc2L, even in caffeine-containing medium. In contrast,
      once forward propagation from Oc1 to Oc2L and oscillatory backward propagation
      from Oc2L to Oc1 was established in caffeine-containing medium, signals elicited
      in Oc1 could strongly penetrate the Oc2 even during blockade of NMDA activities,
      when forward penetrating components were dependent on non-NMDARs. These findings
      suggest that: (1) signal behavior and its mechanism between Oc1and Oc2L are the
      same with those between Oc1 and Oc2M; and (2) NMDAR activation results in non
      NMDAR activity, resulting in opening and strengthening of intrinsic signal
      pathways between Oc1 and Oc2. NMDAR-dependent forward and backward propagation
      might be involved in cortical reorganization of the visual cortex.

PMID- 15725403
TI  - Angiotensin II evokes hypotension and renal sympathoinhibition from a highly
      restricted region in the nucleus tractus solitarii.
AB  - Microinjections of low doses (in the femtomolar or low picomolar range) of
      angiotensin II (Ang II) into the nucleus tractus solitarii (NTS) evoke depressor
      responses. In this study we have mapped in the rat the precise location of the
      subregion within the NTS at which Ang II evokes significant sympathoinhibitory
      and depressor responses. Microinjections of 1 pmol of Ang II evoked large
      decreases (>or=20% of baseline) in renal sympathetic nerve activity (RSNA), from
      a highly restricted region in the medial NTS, at or very close to the level 0.2
      mm caudal to the obex. Microinjections of the same dose of Ang II into the
      commissural or lateral NTS at the same rostrocaudal level, or into the medial and
      lateral NTS at the level of the obex evoked significantly smaller
      sympathoinhibitory responses, while microinjections into more rostral or caudal
      levels of the NTS evoked significant sympathoinhibitory responses even less
      frequently. In most cases (71%), the sympathoinhibitory responses were
      accompanied by depressor responses, the magnitudes of which were also greater
      within the medial NTS at the level 0.2 mm caudal to obex, as compared to the
      surrounding subregions. The results demonstrate that the cardiovascular effects
      of Ang II in the NTS are highly site-specific. Taken together with previous
      studies, the results also indicate that the neurons in the NTS that mediate the
      Ang II-evoked sympathoinhibition are a discrete subgroup of the population of
      sympathoinhibitory neurons within the nucleus.

PMID- 15725404
TI  - Localization and characterization of cGMP-immunoreactive structures in rat brain
      slices after NO-dependent and NO-independent stimulation of soluble guanylyl
      cyclase.
AB  - Possible differences in the localization of the cGMP response were investigated
      in rat brain coronal slices after in vitro incubation and NO-dependent or NO
      independent stimulation of soluble guanylyl cyclase (sGC). Dose-dependent
      stimulation of cGMP synthesis by the NO donors, sodium nitroprusside, S
      nitrosoglutathione, 3-morpholinosydnonimine and diethylamino NONOate was studied
      in the somatoparietal cortex, the hippocampus and the thalamus. cGMP accumulation
      was evaluated using a radioimmunoassay and by measuring cGMP-immunofluorescence
      using image analysis. All four NO donors induced similar cGMP staining patterns
      in the somatoparietal cortex, the hippocampus and the thalamus. NO-mediated cGMP
      synthesis in the cortical areas colocalized predominantly with the acetylcholine
      transporter and occasionally with parvalbumin (GABAergic cells) or the neuronal
      glutamate transporter. Incubation of the slices in the combined presence of a NO
      donor and the NO-independent activators YC-1 or BAY 41-2272 strongly potentiated
      cGMP synthesis and induced abundant cGMP-immunoreactivity in cortical GABAergic
      and glutamatergic cells. These findings indicate that the mechanism of NO release
      from the NO donors used does not determine the location of the cGMP response. The
      results suggest that YC-1 and BAY 41-2272 trigger a NO-sensing mechanism in cells
      in which the sGC is otherwise not sensitive to NO.

PMID- 15725405
TI  - Overlap and interdigitation of cortical and thalamic afferents to dorsocentral
      striatum in the rat.
AB  - Dorsocentral striatum (DCS) is an associative region necessary for directed
      attention in rats. DCS is defined as the main region in which axons from
      ipsilateral medial agranular cortex (AGm) terminate within the striatum. In this
      double-labeling study, we placed a green axonal tracer in area AGm and a red one
      in an additional brain region. We examined the spatial relationship between
      terminals from area AGm and other portions of the cortical-basal ganglia-thalamic
      cortical network involved in directed attention and its dysfunction, hemispatial
      neglect, in the rat. These include lateral agranular cortex (AGl), posterior
      parietal cortex (PPC), ventrolateral orbital cortex (VLO), and secondary visual
      cortex (Oc2M). One important finding is the presence of a dense focus of labeled
      axons within DCS after injections in cortical area PPC or Oc2M. In these foci,
      axons from PPC or Oc2M extensively overlap and interdigitate with axons from
      cortical area AGm. Additionally, retrograde labeling of striatal neurons, along
      with double anterograde labeling, suggests that axons from cortical area AGm and
      AGl cross and possibly make contact with the dendritic processes of single medium
      spiny neurons. Axons from thalamic nucleus LP were observed to form a dense band
      dorsal to DCS which is similar to that seen following PPC injections, and a
      significant number of LP axons were also observed within DCS. Projections from
      thalamic nucleus VL are present in the dense dorsolateral AGm band that abuts the
      external capsule, are densest in the dorsolateral striatum, and were not observed
      in DCS. These results extend previous findings that DCS receives input from
      diverse cortical areas and thalamic nuclei which are themselves interconnected.

PMID- 15725407
TI  - Spreading depression in vivo potentiates electrically-driven responses in frog
      optic tectum.
AB  - This is the first description of an in vivo potentiation phenomenon associated to
      spreading depression (SD) in the frog optic tectum. Field potential responses
      electrically-elicited from the optic tract and recorded in the optic tectum
      disappeared during KCl-elicited SD and recovered 10-20 min thereafter. Post-SD
      responses reached amplitudes 10-30% higher than their pre-SD values (P<0.05),
      indicating a potentiation effect. Current source density analysis of the tectal
      depth profiles of field-potential responses, as well as the calculation of the
      post-SD intratectal conductance changes, also supported the potentiation
      phenomenon. This in vivo potentiation lasted for 40-90 min, suggesting a post-SD
      enhancement of synaptic transmission, which may be important in understanding
      mechanisms of brain disfunctions like epilepsy.

PMID- 15725408
TI  - Restoration of learning ability in hyperammonemic rats by increasing
      extracellular cGMP in brain.
AB  - Intellectual function is impaired in patients with hyperammonemia and hepatic
      encephalopathy. Chronic hyperammonemia with or without liver failure impairs the
      glutamate-nitric oxide-cGMP pathway function in brain in vivo and reduces
      extracellular cGMP in brain as well as the ability of rats to learn a Y maze
      conditional discrimination task. We hypothesized that the decrease in
      extracellular cGMP may be responsible for the impairment in learning ability and
      intellectual function and that pharmacological modulation of the levels of cGMP
      may restore learning ability. The aim of this work was to try to reverse the
      impairment in learning ability of hyperammonemic rats by pharmacologically
      increasing extracellular cGMP in brain. We assessed whether learning ability may
      be restored by increasing extracellular cGMP in brain by continuous intracerebral
      administration of: (1) zaprinast, an inhibitor of the phosphodiesterase that
      degrades cGMP or (2) cGMP. We carried out tests of conditional discrimination
      learning in a Y maze with control and hyperammonemic rats treated or not with
      zaprinast or cGMP. Learning ability was reduced in hyperammonemic rats, which
      needed more trials than control rats to learn the task. Continuous intracerebral
      administration of zaprinast or cGMP restored the ability of hyperammonemic rats
      to learn this task. Pharmacological modulation of extracellular cGMP levels in
      brain may be a useful therapeutic approach to improve learning and memory
      performance in individuals in whom cognitive abilities are impaired by different
      reasons, for example in patients with liver disease who present hyperammonemia
      and decreased intellectual function.

PMID- 15725406
TI  - Estradiol to aged female or male mice improves learning in inhibitory avoidance
      and water maze tasks.
AB  - Although 17beta-Estradiol (E2) improves cognitive performance of aged female
      mice, its mnemonic effects when administered post-training to aged male mice have
      not been examined. E2 (10 microg, SC) or oil vehicle was administered to intact,
      24-month-old female or male congenic (primarily C57BL/6 background) mice
      immediately after training in the inhibitory avoidance or water maze tasks.
      Following behavioral testing, effects of 1 or 24 h of E2 exposure on hippocampal
      levels of E2 and brain-derived neurotrophic factor (BDNF) were examined. Female
      and male mice administered E2 showed significantly better performance in the
      inhibitory avoidance task than did vehicle-administered mice. When tested 24 h
      after training, mice that received E2 had significantly longer latencies to cross
      over to the shock-associated side of the chamber than did vehicle-administered
      mice. Female or male mice administered E2 showed significantly better performance
      in the reference memory aspect of the spatial water maze task. When tested 30 min
      after training, mice administered E2 had shorter latencies to, and spent longer
      swimming in, the quadrant that the hidden platform had previously been located
      in. E2 administration produced physiological levels of E2 in the hippocampus 1
      and 24 h after E2. BDNF levels in the hippocampus were decreased following 1 h of
      E2 exposure compared to vehicle. These findings suggest that E2 to female and
      male mice may overcome age-related deficits in reference memory in an emotional
      or spatial learning task.

PMID- 15725409
TI  - Effects of age and diet on the heavy particle-induced disruption of operant
      responding produced by a ground-based model for exposure to cosmic rays.
AB  - On missions to other planets, astronauts will be exposed to galactic cosmic rays
      which are composed of heavy particles (such as 56Fe) and protons. Exposure to
      these particles can affect the ability of rats to perform a variety of tasks,
      indicating that there is the possibility that the performance capabilities of
      astronauts may be affected. Previous research has shown that diets containing
      blueberry or strawberry extract can ameliorate the deficits produced by
      irradiation using a ground-based analog for exposure to cosmic rays. Rats were
      placed on diets containing 2% blueberry or strawberry extract for 2 months prior
      to exposure to 1.5 Gy of 1 GeV/n 56Fe particles. There were no effects on
      performance of any group of animals when tested on an ascending fixed-ratio
      operant task 6 months following exposure. When tested 12 months after exposure,
      the performance of the radiated animals given blueberry extract did not differ
      from the radiated animals fed the control diet. Both groups performed
      significantly poorer than the non-irradiated controls. There were no differences
      between the non-irradiated animals fed control diet and the radiated animals fed
      the strawberry diet and their performance was significantly better than of the
      radiated rats fed the blueberry or control diets. The results indicate that diets
      containing strawberry extract may provide a significant level of radiation
      protection on exploratory class missions.

PMID- 15725410
TI  - Excitatory stimulation of neurons in the arcuate nucleus initiates central CRF
      dependent stimulation of colonic propulsion in rats.
AB  - It is well established that autonomic control of digestive function is modulated
      by central autonomic neurotransmission. In this context it has been shown that
      digestive function can be modulated by exogenous neuropeptides microinjected into
      specific brain sides. Furthermore, there is considerable evidence suggesting that
      neurons projecting from the arcuate nucleus (ARC) to the PVN may be the source of
      endogenous neuropeptide release in the PVN. Neuronal projections from the ARC
      have been proposed to target corticotropin-releasing factor (CRF)-positive
      neurons in the PVN. Exogenous CRF in the PVN has been shown to modulate digestive
      function like gastric acid secretion and GI motility. Recently we have
      demonstrated that activation of ARC neurons inhibits gastric acid secretion via
      central CRF receptor dependent mechanisms. This poses the question whether
      neuronal activation of the ARC alters digestive function beside gastric acid
      secretion. In the present study we investigated whether CRF pathways in the ARC
      PVN axis are involved in the modulation of colonic motility. First we examined
      the effect of an excitatory amino acid, kainate, microinjected into the ARC on
      colonic motility in anesthetized rats. Colonic motility was measured with a non
      absorbable radioactive marker using the geometric center method. Kainate (120
      pmol/rat) bilaterally microinjected into the ARC induced a significant
      stimulation of colonic propulsion. To assess the contribution of hypothalamic CRF
      to the effects of neuronal stimulation in the ARC on colonic motility we
      performed consecutive bilateral microinjections of an antagonist to CRF receptors
      into the PVN and the excitatory amino acid kainate into the ARC. Microinjection
      of the non-selective CRF receptor antagonist, astressin (100 ng), into the PVN
      abolished the stimulatory effect of neuronal activation in the ARC by kainate on
      colonic motor function. The data indicate that activation of neurons in the ARC
      stimulates colonic motility via CRF-receptor-mediated mechanism in the PVN and
      underlines the important role of the ARC-PVN circuit for the integrative CNS
      regulation of GI function.

PMID- 15725411
TI  - Changes in the substance P-containing innervation of the lumbosacral spinal cord
      in male Wistar rats as a consequence of ageing.
AB  - Quantitative image analysis was used to determine age-related changes in the
      substance P-containing innervation of autonomic and somatic nuclei in the
      lumbosacral spinal cord, which are associated with the control of micturition and
      sexual reflexes. In the upper lumbar segments (L1-L2), significant declines in
      the distribution density of substance P-containing processes were observed in the
      dorsal grey commissure, the intermediolateral cell column and the ventral horn.
      More caudally, at levels corresponding to L5 through S1, significant reductions
      were seen in the dorsal grey commissure and within the sacral parasympathetic
      nucleus. In contrast to these observations, the substance P-immunoreactive
      innervation of the dorsolateral nucleus remained robust in aged animals and was
      not significantly different from young adults. It is possible that these distinct
      age-related patterns of change in substance P-containing innervation, are
      reflected in the urinary/sexual dysfunction's in aged animals.

PMID- 15725412
TI  - Expression of endothelin-1 in the brain and lung of rats exposed to permanent
      hypobaric hypoxia.
AB  - High-altitude hypoxia causes pulmonary hypertension in humans and animals.
      Endothelin-1 (ET-1) is a novel and long-lasting vasoconstrictor. However, no
      study has dealt with the effects of a hypobaric hypoxic environment (HHE) on ET-1
      activity in the brain. We examined 134 male rats permanently exposed to the
      equivalent of 5500 m altitude for 1 to 8 weeks. In these HHE rats, the mean
      pulmonary arterial pressure was significantly raised. The level of ET-1 protein,
      measured by enzyme immunoassay, increased rapidly in the lungs on exposure to
      HHE, but decreased in the brain. The level of ET-1 mRNA, measured by
      semiquantitative RT-PCR, was raised at 1, 4, and 6 weeks' exposure in the lungs
      and at 4 or more weeks' exposure in 3 of 8 brain regions. By in situ
      hybridization and immunohistochemistry of brain sections, ET-1 mRNA and protein
      were detected in the endothelial cells, neurons, and astrocyte-like cells in
      control rats. In HHE rats, the immunoreactive intensity for ET-1 protein
      decreased rapidly with time in these cells within the brain, although a few
      weakly ET-1 protein-positive cells were detected until 8 weeks' exposure to HHE.
      Only a few weakly ET-1 mRNA-positive endothelial cells were detected in any HHE
      rats. Although the reactivity for ET-1 mRNA had decreased significantly in
      neurons and astrocyte-like cells at 1 and 2 weeks' exposure to HHE, it was again
      strong in both types of cells at 4 weeks' exposure to HHE. These results raise
      the possibility that during exposure to HHE, ET-1 production in the lung may play
      a role in the development of pulmonary hypertension, while a decrease in ET-1
      production within the brain may help to protect neurons by preventing or limiting
      the constriction of cerebral microvessels during the hypoxia induced by HHE.

PMID- 15725413
TI  - Effects of 17beta-oestradiol on cerebral ischaemic damage and lipid peroxidation.
AB  - INTRODUCTION: Numerous studies demonstrate oestrogen's neuroprotective effect in
      stroke models, although the mechanisms are unclear. Since oestrogen is an
      antioxidant, we tested the hypothesis that oestrogen reduces stroke-induced
      damage by reducing free radical damage, particularly lipid peroxidation. METHODS:
      Sprague-Dawley rats were ovariectomised and a 17beta-oestradiol (0.25 mg, 21 day
      release) or placebo pellet implanted subcutaneously. Two weeks later, permanent
      middle cerebral artery occlusion (MCAO) was induced by intraluminal filament. At
      2 and 24 h post-MCAO, neurological deficits were assessed. At the 24 h end point,
      plasma oestradiol was measured and brain sections stained with haematoxylin and
      eosin or lipid peroxidation marker, 4-hydroxynonenol (4-HNE) immunohistochemistry
      carried out to measure infarct volume and volume of tissue displaying oxidative
      damage, respectively. RESULTS: Plasma 17beta-oestradiol in oestradiol and placebo
      groups was 72.6+/-38.0 and 9.3+/-7.4 pg/ml (mean+/-SD), respectively. Infarct
      volume was significantly increased (118%) with oestradiol treatment
      (oestradiol=124+/-84.5, placebo=57+/-46.4 mm3, mean+/-SD, P<0.05). The
      relationship between 4-HNE and infarct volume was significantly influenced by
      17beta-oestradiol. Neurological deficits were similar between groups (oestradiol
      median=13, placebo=14, max score=33). CONCLUSION: Two week pre-treatment with a
      high physiological dose of 17beta-oestradiol increased infarct volume after
      permanent MCAO. Although contrary to our original hypothesis, this result
      demonstrates that oestrogen does have the capacity to promote detrimental actions
      in the stroke-injured brain. Given the wide use of oestrogen (contraception,
      osteoporosis and menopause), more research to clarify the influence of oestrogen
      on brain injury is urgently required.

PMID- 15725414
TI  - Effect of GDNF on differentiation of cultured ventral mesencephalic dopaminergic
      and non-dopaminergic calretinin-expressing neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor
      for ventral mesencephalic (VM) dopaminergic neurons. Subpopulations of
      dopaminergic and non-dopaminergic VM neurons express the calcium-binding proteins
      calbindin (CB) and calretinin (CR). Characterization of the actions of GDNF on
      distinct subpopulations of VM cells is of great importance for its potential use
      as a therapeutic molecule and for understanding its role in neuronal development.
      The present study investigated the effects of GDNF on the survival and
      morphological differentiation of dopaminergic and non-dopaminergic neurons in
      primary cultures of embryonic day (E) 18 rat VM. As expected from our results
      obtained using E14 VM cells, GDNF significantly increased the morphological
      complexity of E18 CB-immunoreractive (CB-ir), tyrosine hydroxylase (TH)-ir, and
      CR-ir neurons and also the densities of CB-ir and TH-ir neurons. Interestingly,
      densities of E18 CR-ir neurons, contrarily to our previous observations on E14 CR
      ir neurons, were significantly higher after GDNF treatment (by 1.5-fold).
      Colocalization analyses demonstrated that GDNF increased the densitiy of
      dopaminergic neurons expressing CR (TH+/CR+/CB-), while no significant effects
      were observed for TH-/CR+/CB- cell densities. In contrast, we found that GDNF
      significantly increased the total fiber length (2-fold), number of primary
      neurites (1.4-fold), number of branching points (2.5-fold), and the size of
      neurite field per neuron (1.8-fold) of the non-dopaminergic CR-expressing neurons
      (TH-/CR+/CB-). These cells were identified as GABA-expressing neurons. In
      conclusion, our findings recognize GDNF as a potent differentiation factor for
      the development of VM dopaminergic and non-dopaminergic CR-expressing neurons.

PMID- 15725415
TI  - Spinal dorsal horn neuron response to mechanical stimuli is decreased by
      electrical stimulation of the primary motor cortex.
AB  - Motor cortex stimulation (MCS) has been used clinically as a tool for the control
      for central post-stroke pain and neuropathic facial pain. The underlying
      mechanisms involved in the antinociceptive effect of MCS are not clearly
      understood. We hypothesize that the antinociceptive effect is through the
      modulation of the spinal dorsal horn neuron activity. Thirty-two wide dynamic
      range spinal dorsal horn neurons were recorded, in response to graded mechanical
      stimulation (brush, pressure, and pinch) at their respective receptive fields,
      while a stepwise electrical stimulation was applied simultaneously in the motor
      cortex. The responses to brush at control, 10 V, 20 V, and 30 V, and recovery
      were 11.5+/-1.6, 12.1+/-2.6, 11.1+/-2.2, 10.5+/-2.1, and 13.2+/-2.5 spikes/s,
      respectively. The responses to pressure at control, 10 V, 20 V, and 30 V, and
      recovery were 33.2+/-6.1, 22.9+/-5.3, 20.5+/-5.0, 17.3+/-3.8, and 27.0+/-4.0
      spikes/s, respectively. The responses to pinch at control, 10 V, 20 V, and 30 V,
      and recovery were 37.2+/-6.4, 26.3+/-4.7, 25.9+/-4.7, 22.5+/-4.3, and 35.0+/-6.2
      spikes/s, respectively. It is concluded that, in the rat, electrical stimulation
      of the motor cortex produces significant transient inhibition of the responses of
      spinal cord dorsal horn neurons to higher intensity mechanical stimuli without
      affecting their response to an innocuous stimulus.

PMID- 15725416
TI  - Function of neuropeptide Y and agouti-related protein at weaning: relation to
      corticosterone, dietary carbohydrate and body weight.
AB  - Neuropeptide Y (NPY) and agouti-related protein (AgRP), potent stimulants of
      feeding, have been linked in adult rats to both corticosterone (CORT) and dietary
      carbohydrate. To understand the significance of this relationship early in life,
      measurements were taken of these parameters at different ages around weaning, in
      rats given a choice of macronutrient diets or maintained on a carbohydrate-rich
      diet. The results demonstrate that, in both male and female rat pups, the
      expression and production of NPY and AgRP in the arcuate nucleus (ARC) peak on
      postnatal day 21 (P21), compared to P15 before weaning and P27 after weaning.
      These elevated levels of peptide were associated with peak levels of CORT and
      glucose and also a strong, natural preference for carbohydrate at weaning, which
      accounted for 55-65% of the pups' total diet. In subgroups defined by their body
      weight at these stages, rats with as little as 4% lower body weight (compared to
      higher weight pups) had 30-60% greater expression of NPY and AgRP in the ARC and
      elevated levels of CORT, with no difference in leptin or insulin. This response
      was significantly more pronounced at P21 than at P15 or P27. The importance of
      carbohydrate during this stage was suggested by additional results showing
      elevated NPY expression, CORT levels, body weight and inguinal fat pad weights in
      P27 pups raised on a 65% carbohydrate diet vs. 45% carbohydrate. These results
      suggest that hypothalamic NPY and AgRP, together with CORT, have glucoregulatory
      as well as feeding stimulatory functions that help mediate the transition from
      suckling of a fat-rich diet to independent feeding of a carbohydrate-rich diet.
      During this critical period, the carbohydrate together with the peptides and CORT
      provide the important signals, including elevated glucose, that promote de novo
      lipogenesis and enable weanling animals to survive periods of food deprivation.

PMID- 15725417
TI  - Brn-3a deficiency increases tyrosine hydroxylase-immunoreactive neurons in the
      dorsal root ganglion.
AB  - Immunohistochemistry for tyrosine hydroxylase (TH) was performed on the dorsal
      root ganglia (DRG) in wild-type, heterozygous and Brn-3a knockout mice at
      embryonic day 18.5. TH-immunoreactive (-IR) neurons were detected in the DRG of
      wild-type and heterozygous mice, but their proportion was greatly increased by
      the loss of Brn-3a function (wild-type and heterozygot, 8.4%; knockout, 20.9%).
      IR neurons were of various sizes in wild-type (mean+/-S.D.=118.1+/-55.4 microm2,
      range=26.6-306.3 microm2) and heterozygous mice. In the knockout mice, however,
      TH-IR neurons were mostly small (mean+/-S.D.=68.2+/-34.3 microm2, range=11.8
      166.8 microm2). The present study suggests that Brn-3a may normally suppress TH
      expression in many small DRG neurons but activate TH expression in large DRG
      neurons.

PMID- 15725418
TI  - Experimental tooth movement upregulates preproenkephalin mRNA in the rat
      trigeminal nucleus caudalis and oralis.
AB  - Levels of preproenkephalin mRNA expression in trigeminal subnucleus complex by
      noxious tooth movement stimuli were examined using in situ hybridization. At 24
      h, preproenkephalin mRNA expression was significantly upregulated in the
      ipsilateral trigeminal subnucleus caudalis (P<0.05), and in the subnucleus oralis
      (P<0.05). These findings suggested that enkephalinergic inhibitory systems could
      be activated during tooth movement, and that subnucleus oralis may be involved in
      modulation of the nociception, as well as the subnucleus caudalis.

PMID- 15725419
TI  - Chronological changes of neurofilament 200 kDa immunoreactivity in the lateral
      olfactory tract after transient forebrain ischemia in gerbils.
AB  - This study was carried out to investigate the transient ischemia-induced changes
      of neurofilament 200 kDa (NF-200) immunoreactivity and protein content in the
      gerbil lateral olfactory tract (LOT) after 5 min of transient forebrain ischemia.
      Weak NF-200 immunoreactivity was detectable in the LOT in the sham-operated
      group. In this group, a few somata of mitral cells showed weak NF-200
      immunoreactivity. One day after transient ischemia, NF-200 immunoreactivity in
      the LOT was increased significantly. NF-200 immunoreactivity in the LOT by 15
      days after ischemia was similar to that in the 1 day post-ischemic group. In this
      time period, strong NF-200 immunoreactivity was expressed in the mitral cell
      processes, but the immunoreactivity in the mitral cell somata was significantly
      decreased. Thereafter, NF-200 immunoreactivity in the LOT was decreased
      significantly by 30 days after ischemic insult. At this time after ischemia, NF
      200 immunoreactivity in the mitral cell dendrites was significantly decreased.
      The result of Western blot study showed that the pattern of NF-200 expression was
      similar to that of immunohistochemistry after ischemia-reperfusion. Our result
      suggests that changes of NF-200 protein in the gerbil LOT may be related to
      response to ischemic damage and that the axonal transport followed transient
      ischemia may be disturbed.

PMID- 15725420
TI  - Bilateral projection of functionally characterized trigeminal oralis neurons to
      trigeminal motoneurons in cats.
AB  - Intracellular Neurobiotin-injections were used to label functionally identified
      neurons in the rostro-dorsomedial part of the trigeminal oral nucleus (Vo.r) in
      the cat. The labeled Vo.r neurons with the mechanoreceptive field in oral tissues
      innervated bilaterally either jaw-opening motoneurons or jaw-closing motoneurons.
      This result suggests that Vo.r neurons play an important role in sensory-motor
      reflexes responsible for coordination of bilaterally symmetrical jaw movements.

PMID- 15725421
TI  - Lack of association between prepulse inhibition and antisaccadic deficits in
      chronic schizophrenia: implications for identification of schizophrenia
      endophenotypes.
AB  - Individuals with schizophrenia, compared to healthy individuals, are known to
      exhibit deficient prepulse inhibition (PPI) of the startle response as well as
      reduced performance on the antisaccade task. There is evidence for genetic
      transmission of both PPI and antisaccadic abnormalities in schizophrenia. It has
      been suggested that PPI and antisaccade measures identify separate
      endophenotypes, on the basis of a lack of relationship between PPI and
      antisaccade deficits in patients with schizotypal personality disorder. However,
      given that patients with schizotypal personality disorder are unlikely to
      manifest all the abnormalities associated with schizophrenia, it is important to
      determine that there is no relationship present between these two abnormalities
      in people affected with schizophrenia. The main objective of this investigation
      therefore was to establish the lack of the association between PPI and
      antisaccade deficits in schizophrenia in two independent studies. Study 1
      involved 39 patients with schizophrenia and 14 healthy controls and study 2
      involved 35 patients with schizophrenia and 22 healthy controls. PPI
      (uninstructed paradigm) of the acoustically elicited startle (eye blink) was
      measured electromyographically. Antisaccadic eye movements (standard, non-overlap
      version) were measured using infrared oculography. Patients displayed reduced PPI
      and a lower percentage of correct antisaccades relative to healthy controls in
      both studies. As expected, no relationship occurred between PPI and the
      percentage of correct antisaccade responses in either group. It is concluded that
      PPI and antisaccade abnormalities in schizophrenia represent separate
      endophenotypes, reflecting the functions of different genetic aetiologies and
      different or only partially overlapping neural systems.

PMID- 15725422
TI  - Psychometric schizotypy modulates levodopa effects on lateralized lexical
      decision performance.
AB  - Emergence of psychotic thought has been related to a breakdown in left-hemisphere
      language dominance. Dopamine (DA) is implicated in both psychotic pathology and
      modulation of the semantic system. The present study explored whether controlled
      DA administration modulates basic language functions: (1) in general and/or (2)
      as a function of schizophrenia-associated thought. Forty healthy men performed a
      tachistoscopic lexical decision task. Participants' performance was also analyzed
      as a function of their positive (magical ideation, MI) and negative (physical
      anhedonia, PHYSAN) schizotypal features. Half of the subjects received 200 mg
      levodopa, the other half a placebo. Our findings showed that pharmacological
      treatment per se did not influence task performance, but influenced laterality
      patterns as a function of participants' schizotypal features. In the placebo, but
      not in the levodopa group, right hemisphere language contribution increased as a
      function of increasing MI scores. In the levodopa, but not in the placebo group,
      superior left hemisphere lexical decision performance was related to increasing
      PHYSAN scores. The findings from both substance groups suggest that in the
      healthy brain, a DA agonist restores left-hemispheric dominance for language by
      reducing right-hemispheric contribution with respect to a positive schizotypal
      trait and by increasing left-hemispheric specialization with respect to a
      negative schizotypal trait. We conjecture that the healthy brain compensates
      through intact neurochemical mechanisms an increased DA concentration, in
      particular for persons with elevated positive psychotic-like features.

PMID- 15725423
TI  - Older schizophrenia patients have more disrupted sleep and circadian rhythms than
      age-matched comparison subjects.
AB  - Patient reports and laboratory studies suggest schizophrenia patients have
      disrupted sleep across age groups. Studies have not compared overall sleep/wake
      patterns or circadian (24-h) activity rhythms of older community dwelling
      schizophrenia patients to matched comparison subjects. This study examined
      whether older schizophrenia patients had more disrupted sleep/wake patterns and
      circadian activity rhythms than age- and gender-matched normal comparison
      subjects (NCS). Twenty-eight older schizophrenia patients and 28 age- and gender
      matched NCS were studied with three days of continuous wrist actigraphy.
      Nighttime and daytime actigraphically estimated sleep and wake, circadian
      activity rhythms and light exposure patterns were compared with and without years
      of education as a covariate. Patients spent longer in bed, had more disrupted
      nighttime sleep, slept more during the day, and had less robust circadian rhythms
      of activity and light exposure compared to NCS. Differences persisted in
      education-adjusted analyses. Within patients, working was associated with
      improved sleep and circadian rhythms. Findings suggest the sleep and circadian
      rhythm disruption of older schizophrenia patients was more extensive than that of
      matched NCS suggesting patients' sleep disruption was above and beyond what is
      attributable to advanced age alone. A need exists to develop multicomponent
      interventions to address sleep difficulties specific to older schizophrenia
      patients.

PMID- 15725424
TI  - Extrapyramidal symptoms in unmedicated schizophrenia.
AB  - Studies of spontaneous extrapyramidal symptoms, dyskinesia and parkinsonism, in
      unmedicated schizophrenia are of importance in understanding their underlying
      pathology and relation to the psychosis. This is a study of extrapyramidal
      symptoms using Abnormal Involuntary Movements Scale for dyskinesia and Simpson
      Angus Scale for parkinsonism in 143 schizophrenia patients who never received
      antipsychotic medication. Psychopathology was measured using the Positive and
      Negative Syndrome Scale. Dyskinesia was present in 35% of patients and
      parkinsonism in 15%. The two disorders coexisted in 11 subjects. Orofacial
      dyskinesia, rigidity and tremor were common symptoms noted. There was no
      significant change in the rates and total scores of dyskinesia and parkinsonism
      with gender, age, duration of illness or age at onset of psychosis. Dyskinesia
      was unrelated to psychopathology. Parkinsonism score correlated positively with
      the motor symptom cluster of psychopathology. Dyskinesia and parkinsonism scores
      correlated positively with each other and parkinsonism score discriminated
      presence of dyskinesia. The associations between the spontaneous abnormal
      movements and other aspects of schizophrenia differed from those described in
      treated patients. Dyskinesia and parkinsonism are an integral part of the
      schizophrenia disease process whose relationship with other factors could be
      influenced by antipsychotic drug treatment.

PMID- 15725425
TI  - Plasma dehydroepiandrosterone levels are strongly increased in schizophrenia.
AB  - Dehydroepiandrosterone has been recently recognized as neuroactive steroid with
      several vital neurophysiological activities on membrane receptors, such as N
      methyl-d-aspartate, and gamma-aminobutyric acid receptors and on genomic androgen
      receptors. DHEA does also have an antiglucocorticoid effect. So far, the
      relevance of this neuroactive steroid to psychiatric disorders is not well known.
      In this study, plasma levels of DHEA were determined with a highly sensitive and
      specific gas-chromatography/mass-spectrometry method in 23 outpatients suffering
      from Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia
      compared with 23 healthy control subjects matched for age and sex. Plasma levels
      of DHEA were found to be strongly elevated in the group of schizophrenic patients
      (mean+/-SD=90.9+/-61.4 nmol/l) compared to that of control subjects (mean+/
      SD=24.0+/-17.9 nmol/l) and the difference was highly significant (t=5.018, df=44,
      p<0.0001). This statistically significant difference was also found when we
      divided the groups of schizophrenics and controls in subgroups of males (t=4.536,
      df=24, p=0.0001) and females (t=2.777, df=18, p=0.0124). These results suggest
      that DHEA may have some role in the pathophysiology of schizophrenia due to its
      complex mechanism of action in the brain involving genomic and non-genomic
      components. Therefore, its study may provide further understanding of the
      pathophysiology of psychoses and open new avenues for their treatment.

PMID- 15725427
TI  - White matter hyperintensities and chronicity of depression.
AB  - OBJECTIVE: White matter hyperintensities (WMHs) on T(2)-weighted magnetic
      resonance imaging (MRI) of the brain are associated with advanced age and late
      life depression. Most investigations predominantly found these lesions in frontal
      lobe and basal ganglia supporting the hypothesis of a fronto-striatal dysfunction
      in depression. A prospective study was undertaken to investigate the association
      between extent of WMHs and clinical outcome in elderly depressed patients.
      METHODS: Thirty-one non-demented depressed subjects underwent a 1.5 T cranial MRI
      scan. The MRI scans were analysed in consensus by two experienced radiologists.
      Each MRI scan was assessed for presence and extent of WMHs, which are
      differentiated in periventricular hyperintensities (PVHs) and deep white matter
      hyperintensities (DWMHs). A total of 21 patients of the original cohort of 31
      patients were re-assessed 5 years after baseline assessment. We ascertained the
      severity of depressive symptoms, the longitudinal course of depression, the
      cognitive decline and the global assessment of functioning at follow-up visit.
      RESULTS: (1) Subjects with greater extent of WMHs had a significant higher
      Hamilton Depression Rating Scale (HAM-D) score, (2) had more severe longitudinal
      courses of depression (3) and had a lower Mini-Mental State Examination (MMSE)
      score. CONCLUSIONS: WMHs on MRI are associated with poorer outcome in elderly
      depressed subjects. Further studies are needed to evaluate WHMs as prognostic
      factor for an appropriate treatment decision-making.

PMID- 15725426
TI  - Prevalence and comorbidity of major depressive disorder in young black and white
      women.
AB  - OBJECTIVE: This study reports the prevalence and comorbidity of depression in two
      large samples of black and white young adult women. METHOD: Clinical interviews
      of participants in a follow-up study of the National Heart, Lung, and Blood
      Institute Growth and Health Study (NGHS-Wave II; N=378) were contrasted with a
      subsample of the National Comorbidity Survey (NCS; N=3749) to examine the rates
      and comorbidity of lifetime major depressive disorder in black and white women
      using methodology described by . The sequencing of disorders was also examined to
      determine which disorder was primary. Comorbidity and sequencing were examined
      for alcohol and drug use disorder, panic disorder, specific phobia, social
      phobia, and post-traumatic stress disorder. RESULTS: Prevalence estimates for
      depression, alcohol use disorder, and drug use disorder were higher for white
      women than for black women in both NGHS-Wave II and NCS. Over half of depressed
      participants in both samples had at least one comorbid disorder and depression
      was associated with an increased probability of all the investigated disorders.
      Only one ethnic difference was found in comorbidity, indicating that black women
      were more likely to have comorbid panic disorder than white women were.
      Depression was primary to alcohol and substance use disorders, whereas it was
      secondary to specific phobia and PTSD. CONCLUSIONS: High rates of comorbidity
      were found for both black and white women, though few ethnic differences in
      comorbidity were found. Preventive and treatment interventions are needed to
      address multiple disorders in young adult women.

PMID- 15725428
TI  - Cortical excitability in cocaine-dependent patients: a replication and extension
      of TMS findings.
AB  - Cortical excitability can be assessed by transcranial magnetic stimulation (TMS).
      Previously we observed that TMS motor threshold (MT) was elevated in abstinent
      cocaine-dependent subjects. In the current study we aimed at replicating our
      initial finding, exploring other TMS-based measures of excitability, and
      examining association with personality characteristics. Nineteen cocaine
      dependent and 12 healthy control subjects were examined. Resting and activated
      motor thresholds (RMT and AMT) and duration of the cortical silent period (CSP)
      were examined. The Cocaine Experience Questionnaire (CEQ) was administered to
      assess cocaine-induced psychotic symptoms. The relationship between Minnesota
      Multiphasic Personality Inventory (MMPI) scales and cortical excitability
      measures was also examined. AMT was significantly elevated in cocaine-dependent
      subjects on both hemispheres. RMT was also significantly elevated on the right
      hemisphere. No CSP changes were noted. Patients with cocaine-induced paranoia had
      longer CSPs on the right hemisphere compared to subjects reporting no paranoid
      experiences. The patients displayed significantly elevated scores on several MMPI
      scales, though the scale scores did not correlate with cortical excitability
      measures. These data support our initial finding of decreased cortical
      excitability in abstinent cocaine-dependent subjects. We interpret this finding
      as a compensatory mechanism against the stimulating and epileptogenic effects of
      cocaine.

PMID- 15725429
TI  - A retrospective study of SSRI treatment in adolescent anorexia nervosa:
      insufficient evidence for efficacy.
AB  - Although selective-serotonin-reuptake-inhibitors (SSRI) have been of limited
      efficacy in the treatment of eating disorder psychopathology and comorbid
      symptoms of malnourished patients with anorexia nervosa (AN), there is recent
      data suggesting that SSRI may play a role in preventing relapse among weight
      restored patients. Though some previous studies included patients in late
      adolescence, the vast majority of investigated subjects have been adults. The aim
      of our retrospective study was to assess the effects of SSRI treatment in
      partially weight-restored children and adolescents with AN. Thirty two females
      with AN (mean 14.5+/-1.4 years) were investigated three times during inpatient
      treatment and at 3- and 6-month follow-up for BMI, eating disorder
      psychopathology, depressive symptomology, and obsessive-compulsive symptomology.
      Medication history during inpatient and outpatient treatment was reconstructed at
      the 6-month follow-up. Nineteen patients received SSRI treatment, while 13
      subjects were non-medicated. In comparison to the non-SSRI group, the SSRI group
      had similar BMI and obsessive-compulsive scores, but higher levels of core eating
      disorder psychopathology and depressive symptoms at the start of medication.
      Rates of re-admissions were similar in both groups (SSRI group: 36%, non-SSRI
      group: 31%, Phi: p=0.72). Repeated measures ANOVA revealed no significant group
      with time interactions for BMI-SDS (p=0.84), core eating disorder symptoms (ANIS,
      p=0.79), depression (DIKJ, p=0.75), and obsessive-compulsive (CY-BOCS, p=0.40)
      scores indicating minimal or no effects of SSRI medication on the course of these
      variables. In conclusion, our results challenge the efficacy of SSRI medication
      in the treatment of eating disorder psychopathology as well as depressive and
      obsessive-compulsive comorbidity in adolescent AN. Clinicians should be chary in
      prescribing SSRI in adolescent AN unless randomized controlled trials have
      proofed the benefit of these drugs.

PMID- 15725430
TI  - Maternal immune activation leads to behavioral and pharmacological changes in the
      adult offspring.
AB  - Maternal exposure to viral infection has been associated with an increased risk
      of schizophrenia in the offspring, and it has been suggested that the maternal
      immune response may interfere with normal fetal brain development. Although
      studies in rodents have shown that perinatal viral infections can lead to
      neuropathological and behavioral abnormalities considered relevant to
      schizophrenia, it is not clear whether these consequences are due to the
      infection itself or to the maternal immune response to infection. We show that an
      induction of maternal immune stimulation without exposure to a virus by injecting
      pregnant dams with the synthetic cytokine releaser polyriboinosinic
      polyribocytidilic acid (poly I:C) leads to abnormal behavioral and
      pharmacological responses in the adult offspring. As in schizophrenia, these
      offspring displayed excessive behavioral switching, manifested in the loss of
      latent inhibition and in rapid reversal learning. Consistent with the clinical
      pharmacology of schizophrenia, both deficits were alleviated by antipsychotic
      treatment. In addition, these offspring displayed increased sensitivity to the
      locomotor-stimulating effects of MK-801, pointing to developmental alterations of
      the dopaminergic and/or glutamatergic systems. Prenatal poly I:C administration
      did not produce learning deficits in classical fear conditioning, active
      avoidance, discrimination learning and water maze. These results show that the
      maternal immune response is sufficient to cause behavioral and pharmacological
      alterations relevant to schizophrenia in the adult offspring.

PMID- 15725431
TI  - Verbal and physical non-aggressive agitated behaviors in elderly persons with
      dementia: robustness of syndromes.
AB  - OBJECTIVE: More than a decade ago, different syndromes of agitation were
      identified in elderly nursing home residents, and it was found that these
      syndromes correlate with medical, cognitive, and psychosocial functioning. The
      present study was conducted to examine the robustness of two major syndromes,
      verbal agitation and physical non-aggressive agitation, as assessed via direct
      observations. METHODS: Study participants were 175 elderly persons with dementia
      recruited from 11 nursing home facilities in Maryland. Observations of the
      participants' behavior were conducted using the agitated behaviors mapping
      instrument. RESULTS: The profiles that emerged for physically agitated residents
      and for verbally agitated residents were remarkably similar to those originally
      reported. Specifically, verbally agitated behaviors correlated with female
      gender, with cognitive decline, poor performance of activities of daily living,
      impaired social functioning, and signs of depressed affect. Physically non
      aggressive agitated behaviors correlated with cognitive impairment and with fewer
      concurrent medical diagnoses. CONCLUSIONS: Examining correlates of different
      syndromes of agitated behaviors may provide researchers with valuable information
      that can be used for in-depth analysis of both the characterization and etiology
      of agitation, thus paving the way for the development of interventions that
      target particular types of problem behaviors.

PMID- 15725432
TI  - fMRI investigation on cue-induced smoking craving.

PMID- 15725433
TI  - Improvement in embryo recovery using double uterine flushing.
AB  - The objective of the present study was to evaluate the effects of double uterine
      flushing on the recovery of embryos/ova in cattle. Two hundred and ten embryo
      recovery procedures were conducted using a double uterine flushing method, and
      the results were compared with 432 conventional single-flushing procedures.
      Cyclic Limousin (n = 403) and Guzera (n = 239) donor cows received an
      intravaginal progesterone releasing device and 2 mg of estradiol benzoate on Day
      0. Between Days 5 and 9, donors received decreasing doses of FSH, which ranged
      from 200 to 300 IU (Bos indicus) and 300 to 500 IU (Bos taurus). On the afternoon
      of Day 7, donors received an injection of 500 microg cloprostenol and
      progesterone implants were removed 12 h later (morning of Day 8). Artificial
      insemination was performed between 14 and 26 h after first detection of
      behavioral estrus. Cows were randomly assigned to have embryos recovered by a
      double-flushing method (n = 210) or the conventional single-flushing procedure (n
      = 432). For the double-flushing procedure, after first flushing the whole uterus
      with 1L of Dubelco's Phosphate Buffered Saline (DPBS), a Foley catheter was
      positioned in the uterine body to permit refilling of the uterus with fresh DPBS
      (80-150 mL). The catheter was closed with the plunger of a disposable 5 mL
      syringe, and the donors were allowed to rest in a holding area for 30 min.
      Thereafter, a second flush was performed to recover the solution remaining in the
      uterus. Animals from the control group were subjected to a single uterine flush.
      From 210 double-flushing procedures, 1409 viable embryos were recovered. In
      comparison, from 432 cows receiving the single-flushing procedure, 1993 embryos
      were recovered. Double flushing increased (P < 0.05) the number of embryos
      recovered per procedure compared to single flushing (6.7 +/- 0.4 versus 4.6 +/-
      0.2, respectively; mean +/- S.E.M.). When double flushing was performed, average
      recovered embryos/ova increased (P < 0.05) from 8.3 +/- 0.4 to 12.7 +/- 0.7 in
      Limousin and from 7.9 to 11.5 in Guzera. Also, utilization of double flushing
      increased (P < 0.05) the number of viable embryos from 4.7 +/- 0.3 to 6.9 +/- 0.5
      in Limousin and from 4.5 +/- 0.4 to 6.4 +/- 0.7 in Guzera. Mean total embryos/ova
      was similar (P > 0.05) between the control group and after the first uterine
      flushing in the double-flushing group; therefore, both flushings were conducted
      efficiently. In conclusion, double uterine flushing increased embryo recovery in
      cattle.

PMID- 15725434
TI  - Within-farm variability in age structure of breeding-female pigs and reproductive
      performance on commercial swine breeding farms.
AB  - This study investigated relationships between herd age structure and herd
      productivity in breeding herds; it also investigated a pattern in parity
      proportions of females over 2 years and its relationship with herd productivity
      in commercial swine herds. This study was based on data from 148 commercial farms
      in North America stored in the swine database program at the University of
      Minnesota. The primary selection criterion was fluctuations in breeding-female
      pig (female) inventories over a 2-year interval. Productivity measurements and
      parity proportions of females were extracted from the database. A 24-month time
      plot in proportions of Parity 0 and Parities 3-5 females (mid-parity) was charted
      for each farm. Using these charts, a change in proportions of Parity 0 and mid
      parity for each farm was categorized into patterns: FLUCTUATE (Parity 0 and mid
      parity proportion lines crossed) or STABLE (the two proportion lines never
      crossed). Higher proportions of mid-parity sows were correlated with greater pigs
      weaned per female per year (PWFY; P < 0.01). Farms with a FLUCTUATE (73% of the
      148 farms) pattern had lower PWFY than those with a STABLE pattern (P < 0.01).
      The STABLE farms had higher proportions of mid-parity sows, higher parity at
      culling, higher frequency of gilt deliveries per year, and lower replacement rate
      than the FLUCTUATE farms (P < 0.01). In conclusion, maintaining stable
      subpopulations with mid-parity and Parity 0 are recommended to optimize herd
      productivity.

PMID- 15725435
TI  - Endometritis treatment with a PGF2alpha analog does not improve reproductive
      performance in a large dairy herd in Argentina.
AB  - In Argentina, most dairy cows with endometritis are treated with prostaglandin
      (PGF(2alpha) or its analogs) and insemination is withheld until there are no
      signs of endometritis. The objective of the present study was to evaluate if this
      method of managing endometritis enhances reproductive performance. Three
      experiments were conducted over 4 years in a large farm in the west of Buenos
      Aires province. In Experiment 1, half of the cows diagnosed with endometritis
      (>1.5-fold difference in diameter of uterine horns, as determined by rectal
      palpation) received standard endometritis management (treatment with tiaprost, a
      PGF(2alpha) analog, rectal palpation every 20 days, and withholding of AI until
      endometritis apparently resolved) and the other half was untreated, with AI at
      the first estrus after the voluntary waiting period. Untreated cows were
      inseminated and conceived 20 days earlier than treated cows, and the pregnancy
      rate by Day 90 postpartum was higher in the untreated group. In Experiment 2,
      cows with endometritis were divided into four groups according to the severity of
      symptoms; within each group, cows were allocated to treatment or control, as in
      Experiment 1. Although first service conception rate decreased as endometritis
      severity increased, reproductive performance in treated versus control cows was
      similar to that of Experiment 1 (with no interaction due to degree of
      endometritis). Re-evaluation of the treated cow (to confirm uterine "normality")
      may have been responsible for the delay in conception in both experiments. The
      objective of Experiment 3 was to determine the effects of tiaprost treatment on
      clinically normal postpartum cows (no evidence of endometritis). Tiaprost
      treatment reduced the interval from calving to conception in multiparous cows,
      but it delayed conception and reduced the conception rate in primiparous cows. In
      conclusion, treatment with tiaprost impaired reproductive performance in
      primiparous cows (in the absence of endometritis). Furthermore, the standard
      treatment for endometritis (treatment with a prostaglandin analog and withholding
      insemination until clinical signs abated) impaired reproductive performance and
      increased costs.

PMID- 15725436
TI  - Low oxygen tension during in vitro maturation of porcine follicular oocytes
      improves parthenogenetic activation and subsequent development to the blastocyst
      stage.
AB  - To establish a reliable in vitro maturation system for activation and subsequent
      development as nuclear recipients for the effective production of pig clones, we
      assessed maturation, activation and parthenogenetic development in response to
      the following: (1) type of immature oocytes (cumulus-oocyte complexes (COCs) or
      parietal granulosa plus cumulus-oocyte complexes (GCOCs)); (2) oxygen (O(2))
      tension (5 or 20%); and (3) maturation period (36-60 h). The rate of nuclear
      maturation to metaphase-II (M-II) in the GCOC group (73.0 +/- 3.1%) was higher
      than that in the COC group (P < 0.05, 60.6 +/- 3.5%), but the rates did not
      differ between the 5 and 20% O(2) tension groups. M-II rate increased (P < 0.05)
      to about 70% after 42 h and then remained constant until 60 h of culture. When
      oocytes were matured under 5% O(2) tension and stimulated, the rate of normal
      oocyte activation (a female pronucleus formation and emission of the second polar
      body) was higher (P < 0.05, 38.5 +/- 3.9%) than when oocytes were matured under
      20% O(2) tension (24.5 +/- 3.9%). On the other hand, the rate of normal
      activation was not significantly different between the COC and GCOC groups, and
      the highest (P < 0.05) normal activation rate was obtained in oocytes cultured
      for 48 and 54 h (48.4 +/- 5.5% and 47.9 +/- 8.2%, respectively). When COC and
      GCOC matured for 48 h under 5 and 20% O(2) tension were stimulated and
      subsequently cultured in vitro for 6 days, the rate of blastocyst formation did
      not differ between the oocyte types nor between the O(2) tension groups. However,
      blastocyst quality, as measured by mean total cell number, was significantly
      higher in the 5% O(2) group (P < 0.05, 34.6 +/- 2.0 for COC; 33.8 +/- 1.8 for
      GCOC) compared with the 20% O(2) group (25.9 +/- 1.8 for COC; 27.0 +/- 2.0 for
      GCOC). In conclusion, low O(2) tension (5%) during in vitro maturation of porcine
      oocytes promoted their ability to be activated normally and improved the quality
      of parthenogenetic blastocysts developed in vitro in modified NCSU-37 solutions.
      This knowledge may be applicable for preparation of in vitro matured oocytes with
      good quality as recipient oocytes for generating pig clones.

PMID- 15725437
TI  - Excretion of lumpy skin disease virus in bull semen.
AB  - This work was done to establish the incidence and duration of excretion of lumpy
      skin disease virus (LSDV) in semen of experimentally infected susceptible bulls.
      Six serologically negative bulls 11-20 months of age were experimentally infected
      with a virulent field isolate (strain V248/93) of LSDV. Animals were observed for
      the development of clinical signs, blood was collected until day 90 after
      infection, and semen was collected every second day until day 18, then twice a
      week till day 63 and twice a month until three consecutive samples were negative
      when tested for LSDV by polymerase chain reaction (PCR). An aliquot of each
      sample which tested positive using PCR was inoculated onto cell monolayers for
      the recovery of virus. Two bulls developed severe lumpy skin disease (LSD), two
      bulls showed mild signs and two bulls showed a transient fever only. Multiple
      samples were positive on PCR from both of the severely affected bulls and one of
      the mildly affected bulls; between days 10 and 159, days 8 and 132, and days 10
      and 21 respectively. Only one sample from each of the other three bulls was
      positive on PCR. Virus was only isolated from two samples from one of the
      severely affected bulls and from five semen samples from the other. This study
      confirmed the excretion of LSDV in bovine semen for prolonged periods, even when
      obvious clinical signs of the disease were no longer apparent.

PMID- 15725438
TI  - Ovulation failure and double ovulation in dairy cattle: risk factors and effects.
AB  - Ovulation failure and double ovulation rates were examined in 1917 inseminations
      performed in high-yielding dairy cows under standard commercial conditions. The
      ovulation rate was determined 11 days post-insemination by ultrasound detection
      of at least one corpus luteum in the ovaries. Analyzing the double ovulation and
      pregnancy rates, the study population consisted only of ovulated cows (n = 1792).
      Data were analyzed using logistic regression methods. A failure to ovulate was
      recorded in 125/1917 (6.5%) services: 82/663 (12.4%) during the warm and 43/1254
      (3.4%) during the cool period. Based on the odds ratios, the risk of ovulation
      failure was 3.9 times higher for inseminations performed during the warm period.
      No significant effects of estrous synchronization, milk production and days in
      milk at AI, and service and lactation number on ovulation failure were found.
      Double ovulation was recorded in 277/1792 (15.5%) services: 146 (52.7%)
      unilateral double ovulations (42.5% left versus 57.5% right); 115 (41.5%)
      bilateral double ovulations; and 16 (5.8%) triple ovulations. Double ovulation
      was recorded in 72 (12.4%) and 205 (16.9%) AI during the warm and the cool
      period, respectively. The percentages of double ovulation for first, second and
      third or more lactations were 6.7, 16.6 and 25%, respectively. Double ovulation
      rates for early (less than 90 days), mid- (90-150 days) and late (more than 150
      days) lactation periods were 13, 20.7 and 14.2%, respectively. Reaching estrus
      during the warm period decreased the likelihood of double ovulation by a factor
      of 0.86; the risk of double ovulation was lower in cows with higher milk
      production (a 1 kg increase in milk yield led to a 0.97-fold reduced risk of
      double ovulation); cows in their second and in their third or more lactations
      showed a likelihood of double ovulation (using the first lactation as reference)
      increased by factors of 3.4 and 5.6, respectively; and reaching estrus during the
      early and late lactation period was related to a decreased probability of double
      ovulation (using the mid-lactation period as reference) by factors of 0.56 and
      0.84, respectively. No significant effects of synchronization and service number
      on the double ovulation rate were found. Pregnancy was recorded in 914/1792 (51%)
      services: rates of 53.5% (811/1515) were recorded for single ovulations; 37.2%
      (103/277) for double ovulations: 28.8% (42/146) for unilateral double ovulations;
      45.2% (52/115) for bilateral double ovulations; and 56.3% (9/16) for triple
      ovulations. The likelihood of pregnancy diminished in cows: inseminated during
      the warm period (by a factor of 0.5); inseminated by one particular bull (by a
      factor of 0.33); with higher milk production (a 1 kg increase in milk yield
      decreased the probability of pregnancy by a factor of 0.98); or undergoing
      unilateral (by a factor of 0.31) and bilateral (by a factor of 0.64) double
      ovulation. Logistic regression analysis indicated no significant effects of
      synchronization, days in milk, lactation number and service number on pregnancy
      rate. Collectively, our results indicate that cows showing estrus in conditions
      of heat stress had a high risk of ovulation failure. The effect of milk
      production on double ovulation was negative, whereas lactation number was
      positively correlated with this factor; the highest incidence of double ovulation
      occurring during the mid-lactation period.

PMID- 15725439
TI  - Establishment of pregnancies after serial dilution or direct transfer by
      vitrified equine embryos.
AB  - Experiments were conducted to determine viability of equine embryos in vivo after
      vitrification. In a preliminary study (Experiment 1), embryos were exposed in
      three steps to vitrification solutions containing increasing concentrations of
      ethylene glycol and glycerol (EG/G); the final vitrification solution was 3.4 M
      glycerol + 4.6 M ethylene glycol in a base medium of phosphate-buffered saline.
      Embryos were warmed in a two-step dilution and transferred into uteri of
      recipients. No pregnancies were observed after transfer of blastocysts >300
      microm (n = 3). Transfer of morulae or blastocysts < or = 300 microm resulted in
      four embryonic vesicles (4/6, 67%). In a second experiment, embryo recovery per
      ovulation was similar for collections on Day 6(28/36, 78%) versus Days 7 and
      8(30/48, 62%). Embryos < or = 300 and >300 microm were vitrified, thawed and
      transferred as in Experiment 1. Some embryos < or = 300 microm were also
      transferred using a direct-transfer procedure (DT). Embryo development rates to
      Day 16 were not different for embryos < or = 300 microm that were treated as in
      Experiment 1(10/22, 46%) or transferred by DT (16/26, 62%). Embryos > 300 microm
      (n = 19) did not produce embryonic vesicles.

PMID- 15725440
TI  - Deep freezing of concentrated boar semen for intra-uterine insemination: effects
      on sperm viability.
AB  - The use of deep-frozen boar semen for artificial insemination (AI) is constrained
      by the need for high sperm numbers per dose, yielding few doses per ejaculate.
      With the advancement of new, intra-uterine insemination strategies, there is an
      opportunity for freezing small volumes containing high sperm numbers, provided
      the spermatozoa properly sustain cryopreservation. The present study aimed to
      concentrate (2 x 10(9) spz/mL) and freeze boar spermatozoa packed in a 0.5 mL
      volume plastic medium straw (MS) or a multiple FlatPack (MFP) (four 0.7 mL volume
      segments of a single FlatPack [SFP]) intended as AI doses for intra-uterine AI. A
      single freezing protocol was used, with a conventional FlatPack (SFP, 5 x 10(9)
      spz/5 mL volume) as control. Sperm viability post-thaw was monitored as sperm
      motility (measured by computer-assisted sperm analysis, CASA), as plasma membrane
      integrity (PMI, assessed either by SYBR-14/PI, combined with flow cytometry, or a
      rapid hypo-osmotic swelling test [sHOST]). Sperm motility did not differ
      statistically (NS) between test-packages and control, neither in terms of overall
      sperm motility (range of means: 37-46%) nor sperm velocity. The percentages of
      linearly motile spermatozoa were, however, significantly higher in controls (SFP)
      than in the test packages. Spermatozoa frozen in the SFP (control) and MFP
      depicted the highest PMI (54 and 49%, respectively) compared to MS (38%, P <
      0.05) when assessed with flow cytometry. In absolute numbers, more viable
      spermatozoa post-thaw were present in the MFP dose than in the MS (P < 0.05).
      Inter-boar variation was present, albeit only significant for MS (sperm motility)
      and SFP (PMI). In conclusion, the results indicate that boar spermatozoa can be
      successfully frozen when concentrated in a small volume.

PMID- 15725441
TI  - Survey of zona pellucida antigens for immunocontraception of cats.
AB  - The purpose of this study was to screen a panel of native zona pellucida (ZP)
      antigens isolated from five mammalian species for immunocontraceptive activity in
      the cat (Felis catus). Native soluble-isolated ZP (SIZP) was prepared from the
      ovaries of cows (bZP), cats (fZP), ferrets (feZP), dogs (cZP), and mink (mZP).
      Vaccines were constructed using SIZP from each of the above species encapsulated
      in liposomes suspended in saline and emulsified with Freund's complete adjuvant
      (SpayVac). Female cats were immunized once (n = 3 cats per group). Serum was
      collected for determination of antibody titers against SIZP and for binding of
      antibodies to feline ovaries. All cats responded to immunization by producing
      anti-SIZP antibodies. The most immunogenic SIZP in cats was from mink, followed
      by feZP, cZP, and fZP in descending order. Antibodies had low reactivity for fZP,
      and no reactivity against feline ovaries was detected by immunohistochemistry. A
      breeding trial was commenced 20 weeks after immunization. All cats became
      pregnant, averaging 4.1 +/- 0.7 viable kittens per litter. We have previously
      shown that porcine SIZP is not an effective antigen for immunocontraception of
      cats. In this study, SIZP from five other mammalian species were immunogenic in
      the cat, but ZP antibodies failed to bind to fZP in situ, and fertility was not
      impeded.

PMID- 15725442
TI  - Effects of estradiol-17beta and progesterone supplementation on in vitro nuclear
      maturation of canine oocytes.
AB  - Unlike in other domestic animals, in vitro maturation (IVM) of canine oocytes has
      had limited success. The present study investigated the effect of the estrous
      cycle and estradiol-17beta (E2) or progesterone (P4) supplementation on in vitro
      nuclear maturation of canine oocytes recovered from domestic dog ovaries in
      various reproductive states (follicular, luteal or anestrous stages). Oocytes
      were cultured in serum-free tissue culture medium (TCM)-199 supplemented with
      various concentrations of E2 (Exp. 1: 0, 0.1, 1.0 or 2.0 microg/ml) or P4 (Exp.
      2; 0, 0.5, 1.0 or 2.0 microg/ml) for 72 h to determine the effective
      concentration of hormones. In Exp. 3, in order to investigate the synergistic
      effect of E2 and P4 supplementation, three groups of oocytes were cultured with 2
      microg/ml E2 plus various concentrations of P4 (0, 0.5, 1.0 or 2.0 microg/ml). As
      results, the rate of maturation to metaphase II (MII) stage was significantly
      higher (P < 0.05) in oocytes from the follicular stage supplemented with 2
      microg/ml E2 (14.7%) compared to the other groups (1.5-8.2%). Significantly
      higher (P < 0.05) maturation rate to MII stage was observed in oocytes from the
      follicular stage supplemented with 1.0 (10.0%) or 2.0 microg/ml (10.8%) P4
      compared to the other groups (0-4.8%). Furthermore, more (P < 0.05) oocytes from
      the follicular stage supplemented with 2.0 microg/ml of E2 and P4 (16.6%) were
      matured to MII stage compared to oocytes from the follicular stage supplemented
      with 2.0 microg/ml E2 alone (10.4%) or the other groups of oocytes (0-7.8%).
      Interestingly, compared to 2.0 microg/ml E2 alone (10.4%), supplementation of 2
      microg/ml E2 + 0.5 microg/ml P4 (3.4%) decreased the maturation of oocytes from
      the follicular stage to MII stage. In conclusion, the present study demonstrated
      that supplementation of the culture medium with E2 or P4 alone significantly
      increased maturation of canine oocyte to MII and that P4 supplementation with E2
      further promote or decrease oocyte maturation compared to E2 alone depending on
      P4 concentration.

PMID- 15725443
TI  - Activity of glutathione peroxidase, superoxide dismutase and catalase and lipid
      peroxidation intensity in stallion semen during storage at 5 degrees C.
AB  - Sperm cell membranes are susceptible to peroxidative damage by an excess of
      reactive oxygen species (ROS). Antioxidative defence systems consisting of
      glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT)
      physiologically control the balance between ROS production and neutralization. In
      the present study the hypothesis was tested that lipid peroxidation occurs during
      storage of semen at 5 degrees C and that semen extender has positive effects on
      the antioxidative potential of equine semen. The aim of the study was to
      determine the activity of GSH-Px, SOD and CAT and the concentration of
      thiobarbituric acid reactive substances (TBARS) as an indicator of lipid
      peroxidation in native semen and after addition of extender, cooling and storage.
      Semen was collected from fertile Shetland stallions. In experiment 1, activity of
      antioxidative enzymes was determined immediately after semen collection and after
      24 h storage at 5 degrees C. Enzyme activities were measured in native semen,
      semen diluted with semen extender, spermatozoa resuspended after centrifugation
      in extender and 0.9% NaCl as well as in undiluted and extender-diluted seminal
      plasma. In experiment 2, TBARS concentrations were analysed during storage of
      semen at 5 degrees C for 24 h. Semen storage for 24 h at 5 degrees C did not
      change activity of the examined enzymes. Antioxidative activity was significantly
      higher in extended than in native semen as well as in extended plasma than in
      undiluted plasma. In conclusion, the addition of semen extender increases the
      antioxidative activity in seminal plasma of stallions. Basal antioxidative
      activity in native semen as well as increased activity in extended semen are
      maintained over 24 h storage at 5 degrees C. TBARS content did not increase
      during semen storage. In conclusion, lipid peroxidation does not increase
      substantially during semen storage. The enzymatic antioxidative activity in semen
      apparently prevents ROS formation and is further increased by addition of semen
      extender.

PMID- 15725444
TI  - Various behavioral signs of estrous and their relationship with time of ovulation
      in dairy cattle.
AB  - The objective of this study was to investigate the relationship between various
      behavioral signs of estrous and time of ovulation and, determine which behavioral
      estrous sign(s) best predicted time of ovulation. In total, 94 ovulations were
      observed in 67 Holstein-Friesian dairy cows. Different behavioral estrous signs
      were observed at 3-h intervals and their relation with time of ovulation
      (ultrasound examinations at 3-h intervals) was investigated. In all estrous
      periods, sniffing and chin resting was displayed, while mounting was displayed in
      90% and standing heat in 58% of estrous periods. Estrus was more intense in
      primiparous cows compared to multiparous cows and when more animals were in
      estrus at the same time. Although, these factors influenced intensity of estrous
      behavioral signs, they did not influence time of ovulation. Ovulation occurred
      30.0 +/- 5.1 h after onset of estrus (ranging between 18.5 and 48.5 h) and 18.8
      +/- 4.4 h after end of estrus (ranging between 9.5 and 33.5 h). Although
      informative, these predictors are highly variable between individuals and the
      method used to determine the onset and end of estrus is time consuming this,
      therefore limits in their use as a practical predictor of ovulation. Sniffing and
      chin resting were displayed during the non-estrous period and are therefore, not
      useful predictors of ovulation time. For animals that displayed standing heat,
      onset of standing heat was a good predictor for ovulation time (occurring 26.4 +/
      5.2 h before ovulation). However, standing heat was only displayed in a limited
      number of cows, especially when only one cow was in estrus at a time. Onset of
      mounting was the best predictor for time of ovulation (occurring 28.7 +/- 5.3 h
      before ovulation), and it was displayed in 90% of the estrous periods. However,
      mounting cannot yet be assessed automatically, which limits its practical use as
      ovulation predictor.

PMID- 15725446
TI  - Volume regulatory function and sperm membrane dynamics as parameters for
      evaluating cryoprotective efficiency of a freezing extender.
AB  - In the past years a series of functional assays has been developed to determine
      the structural, morphological and functional integrity of the plasma membrane and
      sperm acrosomal membrane. Cell volume regulation is an important physiological
      function crucial for the success of cryopreservation. In this study, the effects
      induced by freezing-thawing were judged by evaluating the functional
      characteristics of frozen-thawed semen samples submitted to secondary stress such
      as osmotic challenge or incubation under capacitating conditions, following
      cryopreservation. Prior to freezing, dog semen samples were diluted in the
      presence or absence of Equex STM Paste, which contains sodium dodecyl sulphate
      (SDS) as the active ingredient. Cell volume regulation and capacitation and
      calcium ionophore-induced membrane dynamics were assessed in freshly diluted and
      frozen-thawed semen samples by electronic volume measurement and flow cytometry.
      Cryopreservation led to a disturbance of the volume regulatory function and to a
      rapid decrease in the proportion of acrosome-reacted live spermaotozoa. Extender
      containing Equex STM Paste had a protective effect on isotonic cell volume, on
      regulatory function under hypertonic conditions, and on the proportion of live
      acrosome-reacted cells. The evaluation of the functional state of sperm submitted
      to secondary stress after freezing-thawing leads to a more subtle
      characterization of sperm function and helps improve the cryoprotective
      efficiency of the extender.

PMID- 15725445
TI  - Plasma concentrations of bovine pregnancy-associated glycoprotein (bPAG) do not
      differ during the first 119 days between ongoing pregnancies derived by transfer
      of in vivo and in vitro produced embryos.
AB  - Calves derived from IVP embryos may suffer from the large offspring syndrome that
      has been related to effects of in vitro culture on the intrinsic quality of the
      embryo. Limited information is available on the role of the placenta in such
      cases. In this study, bovine pregnancy-associated glycoprotein (bPAG) was used as
      a marker to test whether placental function is influenced by the route of embryo
      production. Therefore, from day 7 until day 119 of ongoing gestations, resulting
      from transfer of MOET (n = 53), IVP-co-culture (n = 21) and IVP-SOF (n = 38)
      embryos, bPAG levels were compared in peripheral plasma of recipients. Plasma
      progesterone levels were compared as well. From day 25 of gestation onwards, bPAG
      could be detected in all recipients and the levels were significantly influenced
      by the day of gestation. Although IVP calves were significantly heavier than the
      in vivo produced calves, this difference was not reflected in the bPAG profiles
      of the embryo production groups. Yet, the mean bPAG level of the three last
      sampling moments (days 105-119) tended to be positively related to the birth
      weight of the calves, irrespective of the embryo production technique.
      Progesterone concentrations were not influenced by route of embryo production,
      but were significantly affected by parity of the recipient and day of gestation.

PMID- 15725447
TI  - Effects of administration of ergotamine tartrate on fertility of yearling beef
      bulls.
AB  - Sixteen yearling bulls were utilized to investigate administration of ergotamine
      tartrate on semen parameters, fertilization, and endocrinology. Bulls were
      allotted to a control diet of cracked corn, corn silage, and soybean meal (CON, n
      = 8) or a diet supplemented daily with 40 microg/kg body weight of ergotamine
      tartrate (ET, n = 8). Blood samples, average daily gain, scrotal circumference
      and rectal temperatures were collected every 14 day. Semen samples were obtained
      every 60 day and evaluated for motility and morphology. Scrotal temperatures were
      obtained by thermography immediately before electroejaculation. Semen from a
      subset of bulls from each treatment was also evaluated for in vitro
      fertilization. Administration of ET increased rectal temperature and resulted in
      lower scrotal temperatures compared to CON bulls (P < 0.05). However, prolactin,
      scrotal circumference, testosterone, and semen motility and morphology did not
      differ between groups throughout the experimental period (224 day). Cleavage
      rates of embryos derived from in vitro fertilization (IVF) with semen of bulls,
      fed with ET, were reduced compared to CON (P < 0.05); however, development of
      cleaved embryos to blastocyst did not differ between treatments. In conclusion,
      extended exposure of bulls to ET appeared to reduce fertilization potential of
      sperm.

PMID- 15725448
TI  - Walking activity at estrus and subsequent fertility in dairy cows.
AB  - Poor detection of estrus, still a major problem in the dairy industry, has
      prompted the development of electronic estrous detection technologies. One of the
      features of estrous behavior is a marked increase in walking activity. The
      objectives of the present study were to evaluate the effects of various
      management factors on walking activity increase at estrus, and the relationship
      between this trait and fertility. Data from 5883 artificial inseminations (AI)
      conducted in two high-producing dairy herds were analyzed. Detection of estrus
      was performed using a pedometer system. Of the total AI investigated, 2072
      (35.2%) resulted in pregnancy. The following data were recorded for each animal
      at AI: herd, lactation number, milk production (average for the 3 days prior to
      AI), lactation stage (early, mid, and late lactation), previous estrous
      synchronization (cloprostenol or progesterone releasing intravaginal device
      [PRID] for animals showing estrus within 7 days of treatment), season (warm
      versus cool period), insemination number following parturition, inseminating
      bull, inseminator, and pedometer measurements. Variables were screened for
      associations with walking activity by analysis of variance (ANOVA) through
      generalized linear model procedures (PROC GLM). Increased parity and milk
      production, and insemination during the warm period were associated with lower
      pedometer measurements. No significant effects of the herd, estrous
      synchronization, and lactation stage were observed. The link between walking
      activity and fertility was determined by applying logistic regression models. We
      detected no significant effects of herd, milk production, estrous
      synchronization, lactation stage, and inseminator on pregnancy rate. A higher
      lactation and insemination number, and insemination during the warm period were
      negatively correlated with the pregnancy rate. The likelihood of pregnancy was
      greater when semen from one of the bulls was used and when physical activity at
      estrus was increased. Our findings indicate that cow and management factors
      contribute intensely to walking activity at estrus, and also reveal a close link
      between increased walking activity and fertility.

PMID- 15725449
TI  - Postpartum ovarian follicular dynamics in primiparous and pluriparous
      Mediterranean Italian buffaloes (Bubalus bubalis).
AB  - The objective of this study was to monitor ovarian function in postpartum
      primiparous and pluriparous Mediterranean Italian buffaloes (Bubalus bubalis)
      during months of increasing daylength. Ovarian ultrasound monitoring was carried
      out for a total of 60 days from calving in 10 primiparous and 10 pluriparous
      buffaloes. Progesterone was determined from calving until a week after first
      postpartum ovulation. The study was undertaken during months of increasing day
      length. Time required for complete postpartum uterine involution was 31 +/- 1.0
      and 33 +/- 1.3 days in primiparous and pluriparous buffaloes respectively (P =
      0.1). The first postpartum ovulation was recorded on 4 primiparous and 8
      pluriparous buffaloes (P = 0.16). Time for first postpartum ovulation to occur
      was 25.5 +/- 6.9 and 15.5 +/- 1.3 days in primiparous and pluriparous buffaloes,
      respectively (P = 0.07). Overall, 8 of the 12 first postpartum ovulations (66.6%)
      occurred in the ovary contra-lateral to the one bearing the gravidic CL, one out
      of 4 in primiparous and 3 out of 8 in pluriparous buffaloes (P = 1.0). Following
      a first postpartum ovulation, 3 primiparous and 4 pluriparous buffaloes displayed
      a complete wave of follicular development leading to a new ovulation. Ovulation
      following parturition was not recorded in 6 primiparous and two pluriparous
      buffaloes for the 60 days of ultrasound monitoring. Growth rate (mm/d) and
      largest size (mm) of first postpartum ovulating follicle was 0.95 +/- 0.18 and
      1.07 +/- 0.07 (P = 0.4), and 13.5 +/- 0.8 and 14.1 +/- 0.4 (P = 0.4) in
      primiparous and pluriparous buffaloes, respectively. Following calving, the total
      number of available antral follicles (> or =2 mm) declined gradually towards the
      end of the study period. Follicles greater or equal to 3 mm in diameter on the
      contrary showed a prominent increase in the first 2 weeks from calving. The
      number of follicles greater or equal to 3 mm in diameter was significantly higher
      in the ovary contra-lateral to the one bearing the gravidic CL. A balance in the
      number of such follicles was reached toward the end of the first month. In
      conclusion, although some follicular activity was recorded in the ovaries of all
      buffaloes, true postpartum resumption of cyclicity in the months of increasing
      daylight hours was delayed in the majority of animals.

PMID- 15725450
TI  - Prenatal development in fishers (Martes pennanti).
AB  - We evaluated and quantified prenatal growth of fishers (Martes pennanti) using
      ultrasonography. Seven females gave birth to 21 kits. The first identifiable
      embryonic structures were seen 42 d prepartum; these appeared to be unimplanted
      blastocysts or gestational sacs, which subsequently implanted in the uterine
      horns. Maternal and fetal heart rates were monitored from first detection to
      birth. Maternal heart rates did not differ among sampling periods, while fetal
      hearts rates increased from first detection to birth. Head and body
      differentiation, visible limbs and skeletal ossification were visible by 30, 23
      and 21 d prepartum, respectively. Mean diameter of gestational sacs and crown
      rump lengths were linearly related to gestational age (P < 0.001). Biparietal and
      body diameters were also linearly related to gestational age (P < 0.001) and
      correctly predicted parturition dates within 1-2 d.

PMID- 15725451
TI  - Effect of estradiol valerate on ovarian follicle dynamics and superovulatory
      response in progestin-treated cattle.
AB  - Three experiments evaluated the effects of estradiol valerate (EV) on ovarian
      follicular and CL dynamics, intervals to estrus and ovulation, and superovulatory
      response in cattle. Experiment 1 compared the efficacy of two norgestomet ear
      implants (Crestar and Syncro-Mate B; SMB) for 9 d (with PGF at implant removal),
      combined with either 5 mg estradiol-17beta and 100 mg progesterone (EP) or 5 mg
      EV and 3mg norgestomet (EN) im at the time of implant insertion on CL diameter
      and follicular wave dynamics. Ovaries were monitored by ultrasonography. There
      was no effect of norgestomet implant. Diameter of the CL decreased following EN
      treatment (P < 0.01). Mean (+/- S.D.) day of follicular wave emergence (FWE) was
      earlier (P < 0.0001) and less variable (P < 0.0001) in EP- (3.6 +/- 0.5 d) than
      in EN- (5.7 +/- 1.5 d) treated heifers. Intervals from implant removal to estrus
      (P < 0.001) and ovulation (P < 0.01) were shorter in EN- (45.7 +/- 11.7 and 74.3
      +/- 12.6 h, respectively) than in EP- (56.4 +/- 14.1 and 83.3 +/- 17.0 h,
      respectively) treated heifers. Experiment 2 compared the efficacy of EP versus EN
      in synchronizing FWE for superovulation in SMB-implanted cows. At random stages
      of the estrous cycle, Holstein cows (n = 78) received two SMB implants (Day 0)
      and were randomly assigned to receive EN on Day 0 or EP on Day 1. Folltropin-V
      treatments were initiated on the evening of Day 5, with PGF in the morning and
      evening of Day 8, when SMB were removed. Cows were inseminated after the onset of
      estrus and embryos were recovered 7 d later. Non-lactating cows had more CL (16.7
      +/- 11.3 versus 8.3 +/- 4.9) and total ova/embryos (14.7 +/- 9.5 versus 7.9 +/-
      4.6) than lactating cows (P < 0.05). EP-treated cows tended (P = 0.09) to yield
      more transferable embryos (5.6 +/- 5.2) than EN-treated cows (4.0 +/- 3.7).
      Experiment 3 compared the effect of dose of EV on ovarian follicle and CL growth
      profiles and synchrony of estrus and ovulation in CIDR-treated beef cows (n =
      43). At random stages of the estrous cycle (Day 0), cows received a CIDR and no
      further treatment (Control), or an injection of 1, 2, or 5 mg im of EV. On Day 7,
      CIDR were removed and cows received PGF. Follicular wave emergence occurred
      within 7 d in 7/10 Control cows and 31/32 EV-treated cows (P < 0.05). In
      responding cows, interval from treatment to FWE was longer (P < 0.05) in those
      treated with 5 mg EV (4.8 +/- 1.2 d) than in those treated with 1 mg (3.2 +/- 0.9
      d) or 2 mg (3.4 +/- 0.8 d) EV, while Control cows were intermediate (3.8 +/- 2.0
      d). Diameter of the dominant follicle was smaller (P < 0.05) at CIDR removal and
      tended (P = 0.08) to be smaller just prior to ovulation in the 5 mg EV group (8.5
      +/- 2.2 and 13.2 +/- 0.6 mm, respectively) than in the Control (11.8 +/- 4.6 and
      15.5 +/- 2.9 mm, respectively) or 1mg EV (11.7 +/- 2.5 and 15.1 +/- 2.2 mm,
      respectively) groups, with the 2mg EV group (10.7 +/- 1.5 and 14.3 +/- 1.7 mm,
      respectively) intermediate. Diameter of the dominant follicle at CIDR removal was
      less variable (P < 0.01) in the 2 and 5mg EV groups than in the Control group,
      and intermediate in the 1mg EV group. In summary, treatment with 5mg EV resulted
      in a longer and more variable interval to follicular wave emergence than
      treatment with 5mg estradiol-17beta, which affected preovulatory dominant
      follicle size following progestin removal, and may have also affected
      superstimulatory response in Holstein cows. Additionally, 5 mg EV appeared to
      induce luteolysis in heifers, reducing the interval to ovulation following
      norgestomet removal. Conversely, intervals to, and synchrony of, follicular wave
      emergence, estrus and ovulation following treatment with 1 or 2 mg EV suggested
      that reduced doses of EV may be more useful for the synchronization of follicular
      wave emergence in progestogen-treated cattle.

PMID- 15725452
TI  - The effect of straw size, freezing rate and thawing rate upon post-thaw quality
      of dog semen.
AB  - Optimal freeze-thaw processes for dog semen will yield a maximal number of
      insemination doses from an ejaculate. The objectives of this study were to
      compare the effects of two straw sizes (0.25- and 0.5-mL French), two freezing
      rates (straws suspended 3.5 and 8 cm above liquid nitrogen) and two thawing rates
      (in water at 37 and 70 degrees C) upon post-thaw quality of dog semen, and to
      determine the best treatment combination. Quality was expressed in terms of the
      percentage progressively motile sperm 5 and 60 min after thawing and the
      percentage of abnormal acrosomes 5 min after thawing. One ejaculate from each of
      eight dogs was frozen. Two straws from each ejaculate were exposed to each of the
      eight treatment combinations. Data were analyzed by means of a repeated measures
      factorial analysis of variance and means compared using Bonferroni's test. Dog
      affected each response variable (P < 0.01). Neither straw size, nor freezing
      rate, nor thawing rate affected motility 5 min after thawing (P > 0.05). Half
      milliliter straws resulted in 5.7% more progressively motile sperm 60 min after
      thawing and 6.5% fewer abnormal acrosomes than 0.25-mL straws (P < 0.05, n = 64).
      The percentage progressively motile sperm 60 min after thawing tended to be
      higher for semen thawed at 70 degrees C compared to 37 degrees C (P < 0.06, n =
      64). Semen thawed in water at 70 degrees C had 6.6% fewer abnormal acrosomes than
      semen thawed in water at 37 degrees C (P < 0.05, n = 64). Freezing rate
      interacted with thawing rate (P < 0.05) in their effects upon acrosomal
      morphology and freezing 8 cm above liquid nitrogen and thawing in water at 70
      degrees C was best. Dog semen should be frozen in 0.5-mL straws, 8 cm above
      liquid nitrogen and thawed in water at 70 degrees C.

PMID- 15725453
TI  - The establishment of an ELISA for the detection of pregnancy-associated
      glycoproteins (PAGs) in the serum of pregnant cows and heifers.
AB  - The pregnancy-associated glycoproteins (PAGs) are a large gene family expressed
      in trophoblast cells of ruminant ungulates. The detection of PAGs (more
      specifically, PAG-1) in maternal serum has served as the basis for pregnancy
      detection in cattle. Unfortunately, PAG-1 and/or antigenically-related PAGs
      exhibit a long half-life in maternal serum (>8 d) and can be detected 80-100 d
      post-partum, thereby producing false positives in animals bred within 60-d of
      calving. The goal of the present studies was to develop a monoclonal-based assay
      that targeted early-pregnancy PAGs whose persistence in maternal serum post
      partum might be relatively short-lived. Three anti-PAG monoclonal antibodies that
      recognized distinct subsets of PAGs were selected and used as trapping reagents
      in a 'sandwich' type of enzyme-linked immunosorbant assay (ELISA). A polyclonal
      antiserum with broad specificity was used for detecting bound PAGs. A total of 42
      cows and heifers were bled daily on day 15, days 22 to 28, and then weekly
      throughout pregnancy and for 10 weeks (approximately 70 d) into the post-partum
      period. The ELISA was able to detect PAG in maternal serum of all animals
      unambiguously by day 28 post-insemination (PAG concentration: 8.75 +/- 3.04
      ng/mL). In maternal serum, PAG concentrations peaked during the week of
      parturition at 588.9 +/- 249.9 ng/mL, and after calving, PAG was completely
      cleared (half-life: 4.3 d) by eight-week post-partum in 38 of 40 of the animals
      tested and was at very low concentrations in the remaining two (1.4 and 4.9
      ng/mL, respectively). In summary, a monoclonal-based assay has been established
      that is sensitive enough to detect PAG in maternal serum by the forth week of
      pregnancy, but does not suffer from carry-over of antigen from a previous
      pregnancy.

PMID- 15725454
TI  - Detection of Neospora caninum in the semen and blood of naturally infected bulls.
AB  - A prospective study was designed to investigate the presence of Neospora caninum
      in semen and blood of eight bulls seropositive to N. caninum using nested-PCR
      procedures. Positive semen and blood samples were bioassayed in a BALB/c nu/nu
      mouse model. Specific anti-N. caninum serological and interferon-gamma (IFN
      gamma) responses were also studied. In parallel, five seronegative bulls acted as
      non-infected controls. All bulls were located in a collaborating AI centre and
      monitored for 22 weeks. Six of eight seropositive bulls showed N. caninum DNA in
      their semen and/or blood samples at some time during the course of the study. In
      all positive semen samples, we consistently found Neospora-DNA in the cell
      fraction and not in seminal plasma. Parasite load, as determined by a real-time
      PCR in nested-PCR positive semen samples, ranged from 1 to 10 parasites/ml. We
      found no association between the presence of N. caninum DNA in semen and blood.
      N. caninum could not be detected in the BALB/c nu/nu mice inoculated with PCR
      positive semen or blood samples. Specific IgG antibody levels in seropositive
      bulls fluctuated over time, at times falling below cut-off level. The response
      was predominantly IgG2, with significant differences compared to control bulls (P
      < 0.05). The overall mean specific IFN-gamma response in seropositive bulls was
      also higher than those observed in the control group (P < 0.05), although
      extensive variation in individual responses was observed among bulls and over
      time. No significant association was found between bulls showing Neospora DNA in
      semen, blood, or both, and specific IgG, IgG1, IgG2, IgM and IgA levels or IFN
      gamma response. This study is the first to report the presence of Neospora DNA in
      semen and blood of naturally-infected bulls. Our observations indicate
      intermittent presence of N. caninum in blood and semen and shedding in semen in
      low numbers.

PMID- 15725455
TI  - Effect of feeding a DHA-enriched nutriceutical on the quality of fresh, cooled
      and frozen stallion semen.
AB  - Eight stallions were used in 2 x 2 crossover study to determine if feeding a
      nutriceutical rich in docosahexaenoic acid (DHA) would improve semen quality.
      Stallions were randomly assigned to one of two treatment groups (n = 4 per
      group). Stallions were fed their normal diet (control) or their normal diet top
      dressed with 250 g of a DHA-enriched nutriceutical. Feeding trials lasted for 14
      week, after which a 14-week washout period was allowed and the treatment groups
      were reversed for another 14 week feeding trial. Feeding the nutriceutical
      resulted in a three-fold increase in semen DHA levels and 50% increase in the
      ratio of DHA to DPA in semen. Sperm motion characteristics in fresh semen were
      unaffected by treatment. After 24 h of cooled semen storage in an Equitainer,
      total and progressive motility did not differ between treatment groups, but sperm
      from stallions fed the nutriceutical exhibited higher velocity and straighter
      projectory (P < 0.05). After 48 h of cooled storage, increases in the percentages
      of sperm exhibiting total motility (P = 0.07), progressive motility (P = 0.06)
      and rapid motility (P = 0.04), were observed when stallions were being fed the
      nutriceutical. For a subset of four stallions, whose progressive sperm motility
      was <40% after 24 h of cooled storage when fed the control diet, feeding the
      nutriceutical resulted in improvements in mean progressive motility of sperm
      after 24 h (P = 0.10) and 48 h (P = 0.03) of storage. Feeding the nutriceutical
      resulted in similar improvements in motion characteristics being observed in
      frozen-thawed semen. While it appears that feeding the nutriceutical may improve
      the motion characteristics of cool-stored stallion semen, it may be most
      beneficial for stallions of marginal fertility whose sperm do not tolerate the
      rigors of cooling and storage. The nutriceutical also appeared to improve the
      freezability of semen. More dramatic improvements in semen quality may be
      observed if modifications in the main fat content of the diet are incorporated
      with the DHA supplement.

PMID- 15725466
TI  - A mighty supporter for WHO classification of myelodysplasia.

PMID- 15725467
TI  - PTEN "meets" DMSO.

PMID- 15725468
TI  - Phenotype and origin of human skeletal muscle-derived hematopoietic progenitors.

PMID- 15725469
TI  - A retrospective analysis of myelodysplastic syndromes with thrombocytosis:
      reclassification of the cases by WHO proposals.
AB  - Myelodysplastic syndromes (MDS) show occasionally thrombocytosis, common feature
      of myeloproliferative diseases (MPD), with the overlapping of both disorders.
      Classically, thrombocytosis has been associated with some MDS subtypes:
      refractory anaemia with ringed sideroblasts (RARS), 5q- syndrome and those MDS
      with 3q chromosome rearrangements. The recent WHO classification recognises an
      unclassifiable MDS/MPD category including some of these disorders. Our aim is to
      determine the frequency of presentation, subtype classification and chromosome
      abnormalities of MDS with thrombocytosis diagnosed in our institution. Between
      1990 and 2003 we studied 317 SMD patients according to FAB and WHO revised
      classifications and identified 22 cases presenting thrombocytosis associated with
      dysplasia, that are analysed in this article.

PMID- 15725470
TI  - The presence of clonal cell subpopulations in peripheral blood and bone marrow of
      patients with refractory cytopenia with multilineage dysplasia but not in
      patients with refractory anemia may reflect a multistep pathogenesis of
      myelodysplasia.
AB  - A clonal origin of hematopoiesis was studied by investigation of X-chromosome
      inactivation patterns (XCIP) in isolated granulocyte, CD14(+) and CD3(+)
      subpopulations obtained from bone marrow and peripheral blood of 36 female
      patients with primary myelodysplastic syndrome (MDS). Clonality was assessed by
      PCR amplification of polymorphic short tandem repeats of the human androgen
      receptor (HUMARA) gene and by investigation of silent polymorphism of iduronate
      sulphatase (IDS) or p55 genes. On the basis of results in a control group of 20
      healthy age related females, a ratio of at least 9:1 between the two alleles was
      considered a significant marker of monoclonal hematopoiesis. Ten of the 11
      patients with advanced forms of MDS (RAEB, RAEB-T, CMML) had clonal granulocytes
      and CD14(+) cells in peripheral blood. In patients with early disease, only 2 out
      of 11 patients (18%) with RA or RARS, according to WHO classification, had clonal
      granulocytes and CD14(+) cells in peripheral blood and bone marrow and 2 other
      patients with 5q-syndrome exhibited extremely oligoclonal granulocyte
      subpopulation in bone marrow. In contrast, we found clonal granulocytes in 12 out
      of 14 patients (86%) with refractory cytopenia with multilineage dysplasia (RCMD)
      and 8 of them simultanously exhibited clonal CD14(+) cells. Estimated 3 years
      survival of patients with early disease and clonal cell subpopulations was 61% as
      compared with 88% in patients without clonal hematopoiesis. Karyotype
      abnormalities were detected in 11 of the 25 females with early disease. Clonal
      patterns were present in 7 out of 8 patients with abberations diagnosed by
      routine cytogenetics, nevertheless, FISH revealed 5q deletion in 3 patients
      without signs of clonality in XCIP assay. No correlation was found between the
      presence of clonal subpopulations and the degree of telomere shortening in early
      MDS. Despite some limitations, the measurement of XCIP remains a sensitive tool
      for diagnosis of the first transforming mutation in the clonal development of MDS
      especially when combined with FISH and when an age related group is used to
      establish an appropriate allele ratio to exclude constitutional or acquired
      skewing. The occurrence of clonal cell subpopulations in most of the RCMD
      patients in contrast to RA may reflect a proposed multistep pathogenesis of MDS
      with dysplastic changes limited to erythropoiesis in early step and with
      subsequent development of multilineage dysplasia. The results also support the
      usefulness of separation of RCMD from 'pure' RA; however, a more complex insight
      combining different molecular techniques performed in a large number of patients
      is needed for refined classification of MDS on the basis of new molecular
      prognostic factors and for indication of more effective targeted therapy.

PMID- 15725471
TI  - Characterization of HTLV envelope seroreactivity in large granular lymphocyte
      leukemia.
AB  - T-cell large granular lymphocyte (T-LGL) leukemia is a rare chronic
      lymphoproliferative disorder of unknown etiology. We have previously reported
      that patients with T-LGL leukemia were seroreactive against BA21, a 34 amino acid
      peptide derived from HTLV-I envelope protein p21. We tested sera from 70 patients
      with T-LGL leukemia and found that 21/70 (30%) of them were seroreactive against
      fusion peptide GST-BA21. In control group of healthy blood donors 3/30 (10%) were
      seroreactive. We synthesized a set of overlapping peptides derived from BA21 and
      tested them against sera from patients. Only a single peptide (p21 env 417-430)
      showed reactivity. We then generated multiple fusion peptides consisting of 5-14
      amino acid residues derived from this peptide and tested them against patient and
      control sera. Shortest peptide giving positive seroreactivity was octapeptide P8
      (p21 env 418-425). Competitive Western blot assay with use of fusion peptides
      revealed that the minimal HTLV-I epitope responsible for seroreactivity found in
      patients with T-LGL leukemia is a decapeptide PP10 (p21 env 417-426). Protein
      Bank (NCBI) search did not reveal any significant homology between PP10 epitope
      and known human proteins. These results further define the epitope responsible
      for HTLV env seroreactivity observed in LGL leukemia.

PMID- 15725472
TI  - Richter's transformation of chronic lymphocytic leukemia. The possible role of
      fludarabine and the Epstein-Barr virus in its pathogenesis.
AB  - Transformation of CLL into a large cell lymphoma has an incidence of 3-5%. We
      have studied 101 cases of CLL treated with fludarabine over a 10-year period
      (1990-2000) and observed a 12% incidence of transformation. In six of 12
      patients, transformation was documented within 4 months following treatment with
      fludarabine. Pathological material, available in nine cases, was investigated for
      latent EBV by staining for LMP-1 by immunohistochemistry and EBERs-1 and 2 by in
      situ hybridisation. LMP-1 and EBERs were demonstrated in three of the nine
      samples. In two cases there was a different pattern of immunoglobulin gene
      rearrangement in the transformed cells assessed by PCR (FR3 fragment) compared to
      the original CLL clone. One of these two cases showed evidence of latent EBV. The
      other seven cases, of which two were EBV positive, showed identical pattern of Ig
      gene rearrangement in both the CLL and the transformed cells. We suggest that the
      relatively high incidence of transformation in this series may be due to
      immunosuppression mainly related to fludarabine, although other agents and prior
      therapies may have also contributed.

PMID- 15725473
TI  - Imatinib mesylate in the treatment of Core Binding Factor leukemias with KIT
      mutations. A report of three cases.
AB  - Aim of this study is to investigate the capability of Imatinib to induce an anti
      leukemic effect in Core Binding Factor (CBF)-leukemia patients presenting either
      with extracellular juxtamembrane or kinase KIT mutations. On the basis of a
      screening analysis for KIT mutations, two patients with a kinase mutation and one
      with extracellular juxtamembrane mutation, in first or subsequent leukemic
      relapse, received 400mg Imatinib twice daily for 30 days. After Imatinib
      discontinuation, bone marrow cells were re-tested to assess the KIT mutational
      status and the chromosomal set. In our experience, none of the treated patients
      had a response by standard criteria; in particular, we did not observe any
      activity against acute myeloid leukemia (AML) associated with KIT kinase
      mutations. However, in the patient with extracellular juxtamembrane mutation,
      Imatinib seems to have some clinical beneficial effect and, most important, is
      able to abrogate the leukemic subclone carrying the mutation. Whether Imatinib,
      in combination with other agents, may play a role in the treatment of AML with
      more sensitive extracellular juxtamembrane KIT mutation remains to be determined.

PMID- 15725474
TI  - Dimethylsulfoxide induces upregulation of tumor suppressor protein PTEN through
      nuclear factor-kappaB activation in HL-60 cells.
AB  - Dimethylsulfoxide (DMSO) has been known to differentiate HL60 cells into
      neutrophil like cells. Here, we provide an evidence for the involvement of tumor
      suppressor PTEN, an antagonist of phosphatidylinositol 3-kinase (PI3K) in the
      DMSO-induced differentiation of HL60 cells. DMSO upregulated PTEN with
      unaffecting the expression of PI3K. The upregulation of PTEN by DMSO lead to the
      decrease of Akt phosphorylation, a downstream of PI3K. The DMSO-induced
      upregulation of PTEN might be mediated by NF-kappaB activation, which was
      evidenced by the blockage of DMSO-induced PTEN upregulation with an NF-kappaB
      inhibitor, pyrrolidine dithiocarbamate (PDTC).

PMID- 15725475
TI  - Establishment and characterization of new cellular lymphoma model expressing
      transgenic human MDR1.
AB  - Multidrug resistance (MDR) due to the expression of the MDR1 gene and its P
      glycoprotein (Pgp) product is a major factor in the prognosis and clinical
      outcome of patients with refractory lymphomas and other malignancies. The aim of
      our study was to establish a lymphoma, cellular system where a de novo
      acquisition of multidrug resistance is specifically related to overexpression of
      a transgenic, human MDR1. A multidrug sensitive lymphoma cell line (LM1) was
      established from a sporadic T-cell lymphoma of BALB/c mouse and was transduced by
      a retroviral vector containing the human MDR1 cDNA. The resultant cell variant
      (LM1/MDR) was characterized in comparison to the parental LM1 cells. The LM1/MDR
      cell variant is cross-resistant to DOX, COL, ACT D and VBL. This cell variant
      expresses the human MDR1 and exhibits de novo functional Pgp activity that can be
      blocked by the Pgp-modulators VRP and KT-5720. The acquired MDR of LM1/MDR is not
      accompanied with gene amplification, alternative splicing or up-regulation of the
      murine endogenous mdr1a, mdr1b, mrp1, mrp2 and mrp3 transporter-genes. Therefore,
      the acquired MDR is, specifically, human MDR1-dependent as it has been found in
      malignant cells of most lymphoma patients. Moreover, this system can be used as a
      model to study MDR and the efficacy of drugs and modulators on malignant cells
      where human Pgp is a major factor of multidrug resistance.

PMID- 15725476
TI  - Cruciferous phytoalexins: antiproliferative effects in T-Jurkat leukemic cells.
AB  - We tested antiproliferative activity of selected cruciferous phytoalexins
      including brassinin, 1-methoxybrassinin, (+/-)-spirobrassin, (+/-)-1
      methoxyspirobrassinin and (+/-)-1-methoxyspirobrassinol, in leukemic Jurkat cell.
      The most effective of the tested phytoalexins was 1-methoxybrassinin with IC(50)
      10 micromol l(-1). However, significant effect of all phytoalexines was also
      determined at concentration 1 micromol l(-1). In 1-methoxybrassinin-treated
      Jurkat cells, we found significant increase in the fraction of cells with a sub
      G(0)/G(1) DNA content, which is considered to be a marker of cell death by
      apoptosis. Apoptosis was also confirmed by the annexin V staining. In summary, 1
      methoxybrassinin exerted potent antiproliferative activity probably due to cell
      cycle arrest and apoptosis induction.

PMID- 15725477
TI  - Coexpression and regulation of the FGF-2 and FGF antisense genes in leukemic
      cells.
AB  - Fibroblast growth factor-2 (FGF-2) is a growth and survival factor whose
      expression is elevated in many hematopoietic malignancies. A natural antisense
      RNA (FGF-AS) has been implicated in the posttranscriptional regulation of FGF-2
      mRNA expression. We demonstrate for the first time that FGF sense and antisense
      RNAs are coordinately expressed and translated in hematopoietic cells and
      tissues. Cytokine stimulation of growth-arrested K562 cells elicited a rapid
      transient increase in FGF-AS mRNA expression followed by a slower but sustained
      increase in FGF-2 mRNA. This was accompanied by a marked increase in the
      expression and nuclear translocation of FGF-2 and the FGF-AS encoded protein,
      GFG/NUDT6. These findings suggest a role for both FGF-2 and GFG proteins in the
      cell survival and proliferation of lymphoid and myeloid tumor cells.

PMID- 15725478
TI  - ABL-MYC retroviral infection elicits bone marrow plasma cell tumors in Bcl-X(L)
      transgenic mice.
AB  - Multiple myeloma is characterized by the accumulation of malignant plasma cells
      in the bone marrow. While there have been many attempts to genetically
      recapitulate this disease in animal models, few reports describe plasma cell
      tumors that exhibit bone marrow involvement. We recently described a Bcl-X(L)
      transgenic mouse that developed polyclonal non-malignant B-cell expansions in the
      bone marrow and lymphoid organs. In this report, we describe induction of plasma
      cell tumors in littermate control and Bcl-X(L) transgenic mice with a retrovirus
      expressing v-Abl and c-Myc. Nearly 100% of the ABL-MYC-infected littermate
      control and Bcl-X(L) mice developed plasma cell tumors. There was no difference
      in tumor latency in young mice infected; however, following ABL-MYC infection,
      aged Bcl-X(L) mice demonstrated a median survival of 9 weeks, while littermate
      control mice demonstrated a median survival of 19 weeks. Interestingly, while
      both littermate control and Bcl-X(L) mice infected with the ABL-MYC retrovirus
      developed extramedullary plasma cell tumors, only the ABL-MYC-infected Bcl-X(L)
      mice, but not the ABL-MYC-infected littermate control mice, developed bone marrow
      plasma cell tumors with characteristic radiolucent bone lesions. Tumor cell
      populations were clonally related, and analysis of tumor immunoglobulin genes
      demonstrated evidence consistent with somatic hypermutation. This report
      implicates an unidentified role of Bcl-X(L) in bone marrow plasma cell tumor
      formation, as ABL-MYC retroviral infection only elicits bone marrow plasma cell
      tumors in mice that ectopically express Bcl-X(L) in their B- and plasma cells.

PMID- 15725479
TI  - Apoptosis inducing bivalent single-chain antibody fragments against CD47 showed
      antitumor potency for multiple myeloma.
AB  - Multiple myeloma is currently considered incurable despite the use of high-dose
      chemotherapy with autologous hematopoietic stem cell transplantation support.
      Here, we show antitumor efficacy of a novel bivalent single-chain antibody
      fragment (scFv) against CD47 in an in vivo myeloma model. We generated two types
      of novel scFv molecules against CD47 having apoptosis-inducing activity for
      leukemic cell lines: a non-covalently linked scFv dimer (diabody) and a
      covalently linked bivalent scFv. Administration of these bivalent scFvs
      significantly prolonged the survival of mice transplanted with KPMM2 human
      myeloma cells. Because bivalent scFvs induced neither ADCC nor CDC, such
      antitumor activity by bivalent scFv is presumably attributable to cell death
      caused by the ligation of CD47. Thus, these apoptosis-inducing scFvs will be
      effective as a novel therapy for multiple myeloma which is considered incurable
      with conventional therapy.

PMID- 15725481
TI  - Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic
      syndromes and chronic myelomonocytic leukemia.
AB  - Myelodysplastic syndromes (MDS) are comprised of a heterogeneous group of stem
      cell disorders characterized by ineffective hematopoiesis and susceptibility to
      transform to acute myeloid leukemia. The molecular pathways underlying disease
      initiation and evolution are still largely unknown. We recently demonstrated that
      acquired mutations in PTPN11 are a major event in JMML and occur with variable
      prevalence in children with other hematologic malignancies, including MDS. Here,
      we investigated contribution of PTPN11 mutations to adult MDS and CMML
      pathogenesis. Our results indicate that PTPN11 lesions might play a role in adult
      MDS/CMML pathogenesis but do not represent a major molecular event.

PMID- 15725480
TI  - The anti-leukemic efficacy of the third generation bisphosphonate ONO5920/YM529.
AB  - Ras proteins are frequently over-expressed in leukemia and contribute to
      leukemogenesis. We evaluated the anti-leukemic efficacy of a new third-generation
      bisphosphonate, ONO5920/YM529 (YM529). YM529 prevents the prenylation of Ras
      proteins and inhibited the growth of leukemic cells including a P-glycoprotein (P
      gp) over-expressing cell line in a concentration- and time-dependent manner by
      inducing apoptosis in vitro. Moreover, YM529 synergistically augmented the anti
      leukemic activities of paclitaxel and daunorubicin in vitro. Importantly, YM529
      prolonged the survival of NOD/SCID mice engrafted with human primary leukemic
      cells. These findings indicate that the YM529 may become a novel molecular
      therapeutic class for treatment of leukemias.

PMID- 15725482
TI  - A single dose of rasburicase is sufficient for the treatment of hyperuricemia in
      patients receiving chemotherapy.
AB  - Hydration, urinary alkalization, and allopurinol are the standard of care in the
      treatment and prevention of hyperuricemia. Rasburicase is a new alternative for
      the management of hyperuricemia in cancer patients. Criteria for the use of
      rasburicase were developed by the Hematology/Oncology Pharmacy and Therapeutics
      Subcommittee of the Detroit Medical Center and implemented in 2003. The
      guidelines limit rasburicase use to one dose, with additional doses as needed,
      compared to the five doses recommended by the manufacturer, in cancer patients
      with hyperuricemia and bulky tumor who require immediate chemotherapy. During the
      period of March to September 2003, eight patients received rasburicase, according
      to the guidelines, for the management of hyperuricemia. One dose of rasburicase
      produced a rapid and sustained therapeutic effect of lowering the plasma uric
      acid levels in all patients. The levels remained below 4 mg/dL throughout the
      administration of chemotherapy for up to 96 h. Utilizing the guidelines resulted
      in a significant cost savings of 100,000 US dollars.

PMID- 15725484
TI  - Aggressive systemic mastocytosis: is there a role for trisomy 8?

PMID- 15725485
TI  - Adults with dyslexia: theta power changes during performance of a sequential
      motor task.
AB  - Performance deficits during cerebellar intensive motor tasks maybe reflected by
      discrepant theta activity in the cerebral cortex. The present experiment examined
      the relationship between performance on a novel motor task and theta activity in
      adults with developmental dyslexia (DD) and an age- and IQ-matched control group
      (CG). Time-locked tonic and phasic lower and upper theta measures were derived
      and separate event-related theta band power (ERBP) scores were calculated for
      each of three experimental trials. The DD made significantly more errors than CG
      during Trials 1 and 2 of the motor task. Tonic theta did not differ between
      groups; however, the DD group displayed a significant decrease in ERBP across all
      trials and sites, specifically in central and parietal regions during Trial 3. No
      significant behavioral or physiological evidence supported the notion of
      conscious compensation (CC). Rather, deficient task performance in the DD group
      was associated with a general inability to recruit sufficient working memory
      processes.

PMID- 15725483
TI  - t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid
      leukemia.
AB  - The rare t(9;11)(p22;p15) translocation is associated with adult acute myeloid
      leukemia (AML) with immature forms. We report a novel fusion of the NUP98 and
      LEDGF genes in a pediatric AML with intermediate characteristics between M2-M3
      French-American-British (FAB) subtypes exhibiting the same chromosomal
      rearrangement. Fluorescence in situ hybridization (FISH) and reverse
      transcriptase-PCR (RT-PCR) studies identified the chimeric transcript product of
      in-frame fusion of NUP98 exon 8 to LEDGF exon 4.

PMID- 15725486
TI  - Slow habituation of induced gamma and beta oscillations in association with
      unreality experiences in schizotypy.
AB  - Highly schizotypal individuals exhibit deficits in attentional processing, in
      particular dysfunctional habituation. This has led to the suggestion that
      abnormal habituation may represent a trait marker of psychotic vulnerability.
      This study examined the difference between high- and low-schizotypal individuals'
      habituation of nonphase-locked gamma and beta-1 oscillations, with and without
      attention. Measures of schizotypy were obtained from 40 participants and
      habituation to different tones was examined over trials of three interval
      lengths, under conditions of attention and inattention. The data showed that all
      participants habituated over trials with long intervals when attending to the
      stimuli. However, those participants who scored high on the unreality subscale
      exhibited significantly less habituation relative to those with low unreality
      scores for the short-interval trials. Furthermore, there was no difference in the
      orienting response to the initial stimuli between these subgroups. These results
      are discussed in terms of a dysfunctional rehearsal process influencing
      habituation for those with high-unreality scores.

PMID- 15725487
TI  - The influence of encoding intention on electrophysiological indices of
      recognition memory.
AB  - The main aim of this study was to further specify the encoding and retrieval
      conditions that determine the success of an ERP-based memory assessment
      procedure, originally derived from lie detection studies. We examined whether
      event-related brain potentials (ERPs) recorded during successful and unsuccessful
      retrieval would vary according to intentional (study) and incidental (repetition)
      encoding conditions. Participants (N=20) were asked to indicate recognition of
      previously studied words (learned targets, p=0.2) and words that were used as
      distractors in a preceding recognition task (repeated targets, p=0.2). Words that
      were recognised elicited a P3 component, which was largely absent for new words
      and words that failed to be recognised. Encoding intention was found to increase
      the P3 amplitude slightly but had no influence on P3 scalp distribution,
      suggesting that the differently encoded targets were similarly processed during
      retrieval but to a different extent. The amplitude difference was explained in
      terms of variance in memory trace strength and decision confidence. With respect
      to negative findings for repeated items in our earlier study (Van Hooff, J.C.,
      Golden, S. 2002. Validation of an event-related potential memory assessment
      procedure: Intentional learning as opposed to simple repetition. J.
      Psychophysiol., 16, 12-22.), it was suggested that the instruction to actively
      retrieve the repeated words was essential for obtaining reliable indications of
      the presence or absence of weak memory traces.

PMID- 15725488
TI  - Age effect on far field potentials from the brain stem after transcutaneous vagus
      nerve stimulation.
AB  - Recently, a new electrophysiological method for the assessment of vagus nerve
      function in the brainstem has been proposed in healthy participants. Before this
      procedure may be applied to patients with neurodegenerative diseases, its
      feasibility in elderly healthy participants and a possible age effect on the
      measurement have to be investigated. The vagus sensory evoked potentials (VSEP)
      after transcutaneous electric stimulation of the sensory auricular branch of the
      vagus nerve have been assessed in healthy younger and elderly participants. VSEP
      measured as far field potentials probably originating in vagus nuclei in the
      brainstem were recorded in 20 of 22 younger as well as in 39 of 43 elderly
      healthy participants. Latencies were significantly longer in the elderly as
      compared to the younger participants, while no clear age effects on amplitudes
      were identified. These results indicate that the assessment of VSEP is feasible
      also in elderly healthy participants. This is a prerequisite for testing this
      method in elderly patients with neurodegenerative diseases like Alzheimer and
      Parkinson disease as a noninvasive tool to detect an affection of the brainstem
      nuclei of the vagus nerve early in their course.

PMID- 15725489
TI  - N400 and category exemplar associative strength.
AB  - The main purpose of this study was to examine if the N400 amplitude can be
      considered an index of category exemplar strength of association in a semantic
      categorization task. Series of six words from a particular semantic category were
      used as context, and the strength of association between the seventh word and the
      category was manipulated. Moreover, subjects were asked to perform two different
      tasks: one consisting of reading the words for comprehension and the other of
      making a decision regarding the congruence of the ending word. Results showed
      that the N400 component was elicited by whichever word that was not the best
      exemplar for the category (atypical members and nonmember of the category). No
      interaction between type of ending word and type of task was found around 400 ms
      poststimuli although the P3b component was present for infrequent stimuli in the
      decision task. It is concluded that the N400 amplitude is sensitive to category
      membership although no specific attention to the semantic relationship between
      words was required.

PMID- 15725490
TI  - Sociotropic cognition moderates stress-induced cardiovascular responsiveness in
      women through effects on total peripheral resistance, but not cardiac output.
AB  - Although cardiovascular disease (CVD) remains the leading cause of mortality in
      women, few studies have examined the role of psychosocial factors in its
      development. This study examined the moderating effects of sociotropic cognition
      (SC), a need for social acceptance and approval, on psychosocial stress-induced
      cardiovascular responsiveness (CVR) and affect reactivity in women. Sixty-eight
      normotensive, college-aged females were randomly assigned to a low or high social
      threat condition. Measures of systolic, diastolic and mean arterial blood
      pressures (SBP, DBP and MAP, respectively), heart rate (HR), cardiac output (CO),
      total peripheral resistance (TPR) and negative affect were collected during rest,
      and under conditions of high vs. low interpersonal threat. A two-step
      hierarchical regression analysis was performed to predict all response variables
      (BPs, HR, CO, TPR and affect). Increases in SBP, DBP, MAP, TPR and negative
      affect were greater in the high threat than low threat condition. Changes in SBP,
      MAP and TPR positively covaried with SC under conditions of high interpersonal
      threat, but showed no significant covariation in the low threat condition. The
      data suggest that an excessive need for social acceptance may contribute to rises
      in BP through an increase in TPR, but not CO under conditions of high social
      threat.

PMID- 15725491
TI  - Evidence for a close relationship between conscious effort and anterior cingulate
      cortex activity.
AB  - The function of the anterior cingulate cortex (ACC) has been discussed in the
      last years in the context of conflict monitoring and error detection. In
      addition, ACC activity has been described in the context of "conscious effort".
      Recent neurophysiological and neuroimaging studies have described a negative
      correlation between ACC activity and reaction times in simple or choice reaction
      time experiments. One suggested explanation for this finding has been that there
      is a relationship between effort and ACC activity. The present ERP-LORETA study
      of healthy volunteers (n=35) was intended to directly investigate this
      relationship. In this experiment, three conditions were investigated: condition I
      was a choice reaction task with the instruction to stay relaxed during the task
      (relaxed condition), condition II was the same choice reaction task with the
      instruction to press the respective button as fast and correct as possible
      (effort condition). Condition III was just listening to the tones without button
      press (control condition). Subjects had to score directly after each experimental
      run on a visual analogue scale the amount of effort they have actually spent. The
      subjects showed significantly shorter reaction times during the high effort
      condition in comparison to the relaxed condition, as well as increased N1
      amplitudes and increased ACC activity. In a subgroup analysis, this effect was
      present only in subjects who were (according to their self-ratings) following the
      instructions closely. These results provide direct evidence for a close
      relationship between conscious effort and ACC activity and suggest the usefulness
      of the applied effort-self-rating.

PMID- 15725492
TI  - Hydration status and cardiovascular function: effects of hydration enhancement on
      cardiovascular function at rest and during psychological stress.
AB  - This study examined the effects of a 3-day enhanced hydration regimen on resting
      cardiac function and reactivity to acute stress. Healthy volunteers (14 male, 14
      female) were assigned to one of two groups: Enhanced Hydration and Normal
      Hydration Group. Participants in the Enhanced Group were given six 1-l bottles of
      water and instructed to drink two bottles a day in addition to normal fluid
      intake for 3 days preceding their laboratory session; no extra water was given to
      the Normal Group. Heart rate (HR), systolic blood pressure (SBP), diastolic blood
      pressure (DBP), cardiac output (CO), stroke volume (SV), and total peripheral
      resistance (TPR) were recorded during a 10-min baseline, 6-min Paced Auditory
      Serial Addition Test (PASAT), 5-min recovery, 5-min intermediate baseline, and 3
      min Cold Pressor Test. Repeated-measures ANOVA revealed a significant Hydration
      GroupxTask interaction for DBP during the cold pressor (p<0.01) with the Enhanced
      Group exhibiting greater DBP reactivity to cold stress relative to the Normal
      Group. Analysis revealed significant Hydration GroupxGender interactions for SV
      and TPR (p<0.05) at rest and during both the PASAT and Cold Pressor Test. Females
      in the Enhanced Group displayed higher SV and lower TPR relative to Enhanced
      Group males, whereas females in the Normal Group displayed lower SV and greater
      TPR relative to Normal Group males. These results suggest that 3-day hydration
      enhancement influences blood pressure reactivity in both men and women, and that
      long-term hydration enhancement is related to resting gender differences in
      cardiac function.

PMID- 15725493
TI  - Synthesis and biological evaluation of new GABA-uptake inhibitors derived from
      proline and from pyrrolidine-2-acetic acid.
AB  - Several synthetic approaches to N-alkylated derivatives of 4-hydroxypyrrolidine-2
      carboxylic acid and 4-hydroxypyrrolidine-2-acetic acid are described. The final
      compounds have been evaluated as potential inhibitors of the GABA transport
      proteins GAT-1 and GAT-3. The biological assays used were based on bovine
      material or porcine brain. As compared to the corresponding 4-unsubstituted
      compounds, the 4-hydroxypyrrolidine-2-carboxylic acid and 4-hydroxypyrrolidine-2
      acetic acid derivatives showed a significant decrease in the inhibitory potency
      at both GAT-1 and GAT-3 with only four compounds having reasonable affinity to
      GAT-1 (IC(50): 5.1, 6.6 and 9.4 microM) or GAT-3 (IC(50): 19.9 microM),
      respectively. The biological data of the 4-hydroxypyrrolidine-2-acetic acid
      derivatives indicates that (2S)-configuration at the C-2 position for potent
      inhibition of GAT-1 and (4R)-configuration at the C-4 position for potent
      inhibition of GAT-3 may be crucial.

PMID- 15725494
TI  - Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9
      trisubstituted beta-carboline derivatives.
AB  - A series of novel 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline
      derivatives was synthesized from the starting material l-tryptophan. Cytotoxic
      activities of these compounds were investigated in vitro. The results showed that
      1,3,9-trisubstituted beta-carboline derivatives had higher cytotoxic activities
      in vitro than the corresponding 1,3-bisubstituted compounds. Among all the
      synthesized 1,3,9-trisubstituted beta-carboline derivatives, the compounds with a
      methyl substituent at position-1 displayed more potent cytotoxic activities,
      furthermore compound 5e having an ethoxycarbonyl substituent at position-3 and a
      pentafluorobenzyl at position-9, respectively, was found to be the most potent
      compounds of this series with IC(50) value of 4 uM against BGC-823 cell lines.
      These data suggested that (1) the cytotoxic potencies of beta-carboline
      derivatives were enhanced by the introduction of appropriate substituents into
      position-1 and position-9 in beta-carboline; (2) the beta-carboline structure
      might be an important basis for the design and synthesis of new antitumor drugs;
      (3) the methyl substituent at position-1, the pentafluorobenzyl group at position
      9 and the ethoxycarbonyl substituent at position-3 were the optimal combination
      for the improvement of cytotoxic activity of the beta-carboline derivatives.

PMID- 15725495
TI  - Synthesis, structure-activity relationship of some new anti-arrhythmic 5
      arylidene imidazolidine-2,4-dione derivatives.
AB  - The synthesis of unsubstituted and halogen substituted 5-arylidene basic amide
      derivatives of imidazolidine-2,4-dione is described. Structural elucidation based
      on X-ray analysis was performed for four representative compounds. The effect of
      the studied compounds on the electrocardiogram was examined in vitro in the non
      working heart perfusion test and that of an anti-arrhythmic activity in the rat
      coronary artery ligation-reperfusion model. The most active compound: (5Z)-(3
      chloro)benzylidene-3-{2-[4-(hydroxyethyl)piperazin-1-yl]-2-oxoethyl}imidazolidine
      2,4-dione has shown properties of the compounds belonging to class Ia, according
      to the Vaughan Williams classification. Chosen compounds evaluated in vivo were
      devoid of anticonvulsant and neurotoxical activity.

PMID- 15725496
TI  - Synthesis and evaluation of new tripeptide phosphonate inhibitors of MMP-8 and
      MMP-2.
AB  - The phosphotryptophan derivative l-Pro-l-Leu-l-(P)Trp(OH)(2) (2b) was reported as
      the first example of left-hand-sideLeft-hand-side inhibitors: inhibitors that
      bind in the unprime region of the enzyme active site, in reference to the
      convention of drawing the unprimed residues of a peptide substrate on the left
      side. [R.P. Beckett et al., Drug Discov. Today 1 (1996) 16-26]. The opposite
      applies to right-hand-side inhibitors. phosphonate inhibitor of MMP-8. Its
      uncommon mode of binding to MMP-8 was mainly ascribed to the presence of the
      proline residue in P(3). Ten new analogues of 2b were obtained by replacement of
      the aminoterminal l-Pro with aminoacid residues bearing small side chains. Most
      of the new analogues show an increase of affinity for MMP-2 and MMP-8, and
      different profiles of selectivity. Computer simulations were performed to explain
      the effects of substitutions on the preferred mode of binding. They reveal that
      most of the new analogues are probably accommodated in the right, rather than
      left-hand side of MMP-8 active site.

PMID- 15725497
TI  - NO-donors, part 9 : diazeniumdiolates inhibit human platelet aggregation and
      induce a transient vasodilatation of porcine pulmonary arteries in accordance
      with the NO-releasing rates.
AB  - Diazeniumdiolates (NONOates), among them a ciprofloxacin-diazeniumdiolate hybrid
      compound, were synthesized and the pH-, temperature- and structure-dependent
      liberation of nitric oxide (NO) was monitored by laser magnetic resonance
      spectroscopy (LMRS). The compounds induced a transient and reversible relaxation
      (EC(50) 8.3-150 nM) of pulmonary arteries independently from intact endothelium
      by stimulation of guanylyl cyclase (sGC). Increase in vascular cGMP was observed
      and blocking sGC with ODQ, an inhibitor of the NO-sensitive guanylyl cyclase,
      induced a rightward shift of the concentration-response curves. Repeated exposure
      did not show homologous desensitization. ADP-induced platelet aggregation (IC(50)
      = 0.15-3 microM, IC(50) for SNP: 2 microM) and collagen-induced aggregation were
      potently inhibited. Preincubation with ODQ also diminished these inhibitory
      effects.

PMID- 15725498
TI  - New triorganotin(IV) derivatives of dipeptides as anti-inflammatory-antimicrobial
      agents.
AB  - New triorganotin(IV) derivatives of dipeptides with general formulae R(3)Sn(HL),
      where R = Me and/or n-Bu and/or Ph and HL is the monoanion of glycylglycine
      (H(2)L-1), glycylvaline (H(2)L-2), glycylleucine (H(2)L-3), glycyltryptophane
      (H(2)L-4) and glycyltyrosine (H(2)L-5) have been synthesized and characterized on
      the basis of infrared, multinuclear NMR and (119)Sn Mossbauer spectroscopic
      studies. All the newly synthesized compounds were examined for their in vivo anti
      inflammatory activity (using the carrageenan-induced paw edema bioassay in rats),
      acute toxicity (LD(50)) and cardiovascular activity. These compounds were also
      screened for their in vitro antimicrobial activity against Staphylococcus aureus
      Mau (29/58) and (78/71), Bacillus subtilis (18/64), Escherichia coli (326/71),
      Candida albicans (Pn-10), Microsporum gypseum and Euglena gracillis. The results
      revealed that triphenyltin(IV) derivatives exhibited anti-inflammatory activity
      comparable to that of phenylbutazone with high safety margin (LD(50) > 500 mg kg(
      1)). Further Ph(3)Sn(Gly-Val) displays a potent cardiovascular activity.
      Moreover, most of the compounds displayed appreciable antibacterial activities
      when compared with ampicillin and norfloxacin. Compounds Ph(3)Sn(Gly-Gly) and
      Ph(3)Sn(Gly-Val) are the most distinctive derivatives identified in the present
      study because of their promising in vivo anti-inflammatory activity and in vitro
      antibacterial activity against gram-positive and -negative bacteria.

PMID- 15725500
TI  - Novel inhibitors of acetyl- and butyrylcholinesterase derived from the alkaloids
      dehydroevodiamine and rutaecarpine.
AB  - Derived from the structures of the alkaloids rutaecarpine and dehydroevodiamine
      (DHED), and the long-known acetylcholinesterase (AChE) inhibitor tacrine,
      respectively, novel compounds were synthesised, including: 13-methyl-5,8-dihydro
      6H-isoquino[1,2-b]quinazolin-13-ium chloride (12), (8Z)-5,6-dihydro-8H
      isoquino[1,2-b]quinazolin-8-imine (13), 5,8-dihydro-6H-isoquino[1,2-b]quinazoline
      (15a), 13-methyl-5,8-dihydro-6H-isoquino[1,2-b]quinazolin-13-ium chloride (16),
      5,7,8,13-tetrahydroindolo [2',3':3,4]pyrido[2,1-b]quinazoline (17), and N-(2
      phenylethyl)-N-[(12Z)-7,8,9,10-tetrahydroazepino [2,1-b]quinazolin-12(6H)
      ylidene]amine (20), respectively. In a first step to evaluate their possible
      applicability for antiamnesic therapy, the inhibition of AChE and
      butyrylcholinesterase (BChE) were determined: compounds 13, 15a, 17, and 20 are
      moderate or strong inhibitors of ChE, the latter two compounds show a 10-fold
      higher affinity to BChE. Compound 12 is a moderate inhibitor of AChE showing
      selectivity towards this enzyme.

PMID- 15725499
TI  - Synthesis and biological evaluation of 6/7-exo-methyl-3beta-(4-iodo)phenyltropane
      2beta-carboxylic acid methyl esters.
AB  - 6beta/7beta-Methyl-2-methoxycarbonyltropinones (3a, 3b) were synthesized and used
      as starting materials in the synthesis of 6beta/7beta-methyl-2beta
      methoxycarbonyl-3beta-phenyltropanes (6a, 6b), 6beta/7beta-methyl-2beta
      methoxycarbonyl-3beta-(4-iodo)phenyltropanes (7a, 7b) and 6beta-methyl-2beta
      methoxycarbonyl-3beta-(4-iodo)phenylnortropane (8). The effect of 6/7-groups was
      evaluated by in vitro receptor binding to dopamine (DAT), serotonin (SERT) and
      norepinephrine (NET) transporters. Introduction of a methyl group at the 6- or 7
      position diminished the overall affinity for the transporters, though mostly to
      NET. In vivo locomotor tests were performed in mice for compounds 7a and 8.
      Compound 8 had no apparent effect on locomotor activity. Compound 7a increased
      locomotion in a wide dose range, but was much less potent than a reference
      compound, 2beta-carbomethoxy-3beta-(4-iodo)phenyl-tropane (beta-CIT).

PMID- 15725501
TI  - Towards a model for the inhibition of choline kinase by a new type of inhibitor.
AB  - Bispyridinium cyclophanes are novel templates for human choline kinase
      inhibitors. Molecular modelling of these compounds suggests three anchorage
      places at the binding site of the enzyme: (i) two anionic centres of the enzyme
      active site separated from each other at a distance of approximately 6.2 A that
      bind the two positively charged nitrogen atoms; (ii) a wide hydrophobic pocket
      that is fulfilled by the upper linker, the benzene ring that links the two amino
      groups; and (iii) a smaller hydrophobic pocket that can accommodate the lower
      benzene ring that links both benzylic carbons. This study may be useful for the
      development of more potent inhibitors of the enzyme.

PMID- 15725502
TI  - Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake
      from labelled seaweed (Chondrus crispus).
AB  - Uptake and depuration experiments of (131)I from labelled seaweed (Chondrus
      crispus) by the edible periwinkle Littorina littorea have been performed.
      Radioiodine concentrations in winkles during uptake followed first-order kinetics
      with an uptake half-time of 1 day, and a calculated equilibrium concentration
      (C(infinity)) of 21 000 Bq kg(-1) resulting in a transfer factor of 0.07 with
      respect to the labelled seaweed used as food. For depuration, a biphasic sequence
      with biological half-lives of 1 and 24 days was determined. The results suggest
      that in general, iodine turnover in periwinkles is slower than observed for other
      molluscs (monophasic biological half-lives in the order of 2-3 days). Both
      environmental media, food and seawater, can be significant sources of radioiodine
      for the winkle.

PMID- 15725504
TI  - Environmental 238U and 232Th concentration measurements in an area of high level
      natural background radiation at Palong, Johor, Malaysia.
AB  - Concentrations of uranium-238 and thorium-232 in soil, water, grass, moss and oil
      palm fruit samples collected from an area of high background radiation were
      determined using neutron activation analysis (NAA). U-238 concentration in soil
      ranged from 4.9 mg kg(-1) (58.8 Bq kg(-1)) to 40.4 mg kg(-1) (484.8 Bq kg(-1)),
      Th-232 concentration ranged from 14.9 mg kg(-1) (59.6 Bq kg(-1)) to 301.0 mg kg(
      1) (1204 Bq kg(-1)). The concentration of U-238 in grass samples ranged from
      below the detection limit to 0.076 mg kg(-1) (912 mBq kg(-1)), and Th-232 ranged
      from 0.008 mg kg(-1) (32 mBq kg(-1)) to 0.343 mg kg(-1) (1.372 Bq kg(-1)). U-238
      content in water samples ranged from 0.33 mg kg(-1) (4.0 Bq L(-1)) to 1.40 mg kg(
      1) (16.8 Bq L(-1)), and Th-232 ranged from 0.19 mg kg(-1) (0.76 Bq L(-1)) to 0.66
      mg kg(-1) (2.64 Bq L(-1)). It can be said that the concentrations of
      environmental U-238 and Th-232 in grass and water samples in the study area are
      insignificant. Mosses were found to be possible bio-radiological indicators due
      to their high absorption of the heavy radioelements from the environment.

PMID- 15725503
TI  - Activities of 210Po and 210Pb in the water column at Kuala Selangor, Malaysia.
AB  - Natural radionuclides, such as (210)Po and (210)Pb were measured in the water
      samples collected from six stations at Kuala Selangor, Malaysia. Results for
      (210)Po and (210)Pb in dissolved and particulate phases have showed the
      difference in distribution and chemical behavior. The fluctuation activities of
      (210)Po and (210)Pb depend on wave action, geology and degree of fresh water
      input occurring at study areas and probably due to different sampling dates. The
      distribution coefficient, K(d), values of (210)Po and (210)Pb ranged from 2.0 x
      10(3)lg(-1) to 265.15 x 10(5)lg(-1), and from 3.0 x 10(3)lg(-1) to 558.16 x
      10(5)lg(-1), respectively. High K(d) values of (210)Po and (210)Pb indicated that
      a strong adsorption of (210)Po and (210)Pb onto suspended particles, and the
      sinking of both nuclides on the seabed at study locations were controlled by the
      characteristics of suspended particles.

PMID- 15725506
TI  - Radionuclide and chemical concentrations in mineral waters at Saratoga Springs,
      New York.
AB  - A project to characterize the radionuclide and chemical components in natural
      spring waters in the vicinity of Saratoga Springs, New York (USA) has been
      completed. As a result of the measured radionuclide and chemical content, eight
      springs were labeled as mineral waters, whereas three springs contained very low
      concentrations of these components. The mineral waters were highly enriched in
      alkaline and alkaline-earth elements, as well as chloride ions. Three isotopes of
      radium ((224)Ra, (226)Ra, (228)Ra) were detected in the mineral waters and
      reached concentrations of 1, 20, and 2 Bq/L, respectively. Overall, the (226)Ra
      isotope constituted about 80% of the total radioactivity measured in the water
      samples. Dissolved uranium concentrations in the mineral waters were very low
      (mean approximately 50 mBq/L).

PMID- 15725505
TI  - Automated radioxenon monitoring for the comprehensive nuclear-test-ban treaty in
      two distinctive locations: Ottawa and Tahiti.
AB  - In preparation for verification of the Comprehensive Nuclear-Test-Ban-Treaty,
      automated radioxenon monitoring is performed in two distinctive environments:
      Ottawa and Tahiti. These sites are monitored with SPALAX (Systeme de Prelevement
      d'air Automatique en Ligne avec l'Analyse des radioXenons) technology, which
      automatically extracts radioxenon from the atmosphere and measures the activity
      concentrations of (131m,133m,133,135)Xe. The resulting isotopic concentrations
      can be useful to discern nuclear explosions from nuclear industry xenon
      emissions. Ambient radon background, which may adversely impact analyser
      sensitivity, is discussed. Upper concentration limits are reported for the
      apparently radioxenon free Tahiti environment. Ottawa has a complex radioxenon
      background due to proximity to nuclear reactors and medical isotope facilities.
      Meteorological models suggest that, depending on the wind direction, the
      radioxenon detected in Ottawa can be characteristic of the normal radioxenon
      background in the Eastern United States, Europe, and Japan or distinctive due to
      medical isotope production.

PMID- 15725507
TI  - Seasonal variation of 228Ra/226Ra ratio in seaweed: implications for water
      circulation patterns in coastal areas of the Noto Peninsula, Japan.
AB  - To examine water circulation patterns of coastal water, 72 seaweed (Sargasso)
      samples and 27 coastal water samples were collected from coastal areas of the
      Noto Peninsula, Japan, during the period from December 1998 to June 2002. The
      (228)Ra and (226)Ra activities of those samples were measured by low-background
      gamma-ray spectrometry. There was a wide range of activities of (228)Ra (0.5
      2Bq/kg-fresh) and (226)Ra (0.5-1.2Bq/kg-fresh) in the Sargasso samples. The
      (228)Ra/(226)Ra activity ratio of Sargasso samples exhibited seasonal variation
      with minimum values in June ((228)Ra/(226)Ra= approximately 1) and maximum values
      in December (1.5-2.5), which was mainly governed by changes in (228)Ra activity.
      It is also notable that the seasonal variation of the (228)Ra/(226)Ra ratio of
      Sargasso is in approximate agreement with that of the ambient coastal water.
      Sargasso samples appear to have retained the (228)Ra/(226)Ra ratio of the ambient
      coastal waters, and the temporal variations in that ratio provide insight into
      seasonal changes in water circulation in the Noto Peninsula coastal area.

PMID- 15725508
TI  - A new general mechanistic river model for radionuclides from single pulse
      fallouts which can be run by readily accessible driving variables.
AB  - This paper presents a new general, process-based river model for substances such
      as radionuclides from single pulse fallouts. The new model has been critically
      tested using data from 13 European rivers contaminated by radiocesium from the
      Chernobyl accident. This modelling approach gives radionuclide concentrations in
      water (total, dissolved and particulate phases; and also concentrations in
      sediments and fish, but the latter aspects are not discussed in this paper) at
      defined river sites. The model is based on processes in the upstream river
      stretch and in the upstream catchment area. The catchment area is differentiated
      into inflow ( approximately dry land) areas and outflow ( approximately wetland)
      areas. The model also accounts for time-dependent fixation of substances in the
      catchment. The catchment area sub-model is based on a previous catchment model,
      which has been tested with very good results for radiocesium, radiostrontium and
      Ca-concentrations (from liming operations). The new river model is simple to
      apply in practice since all driving variables may be readily accessed from maps
      and standard monitoring programs. The driving variables are: latitude, altitude,
      continentality, catchment area, mean annual precipitation, soil type (percentages
      or organic and sandy soils), fallout and month of fallout. Modelled values have
      been compared to independent empirical data from 10 rivers sites (91 data on
      radiocesium in water) covering a wide domain (catchment areas from 4000 to 180
      000 km(2), precipitation from 500 to 960 mm/yr and fallout from 1700 to 660 000
      Bq/m(2)). The new model predicts very well--when modelled values are compared to
      empirical data, the slope is perfect (1.0) and the r(2)-value is 0.90. This is
      good giving the fact that there are also uncertainties in the empirical data,
      which set a limit to the achieved predictive power, as expressed by the r(2)
      value.

PMID- 15725509
TI  - Protective effect of caffeic acid phenethyl ester (CAPE) on myocardial ischemia
      reperfusion-induced apoptotic cell death.
AB  - Occlusion of coronary artery causes cardiomyocyte dysfunction. Reperfusion
      relieves ischemia by providing cells with metabolites and oxygen, thereby
      preventing extensive tissue damage. Although reperfusion salvages the myocardium,
      it also initiates a series of events including myocardial apoptosis and necrosis.
      The common inducers of apoptosis include reactive oxygen species (ROS). Caffeic
      acid phenethyl ester (CAPE) is known as an antioxidative, anti-inflammatory
      effects, may protect myocardial ischemia-reperfusion (MI/R)-induced apoptosis. We
      have previously reported that CAPE reduced MI/R-induced necrosis. Therefore, this
      study was focused to investigate protective effect of CAPE on the distinct form
      of cell death; apoptosis in an in vivo rat model. To produce MI/R, a branch of
      the descending left coronary artery was occluded for 30 min followed by 2 h
      reperfusion. ECG changes, blood pressure (BP), and heart rate (HR) were measured
      before occlusion and continued both occlusion and reperfusion. CAPE (50
      micromol/kg) was given 10 min before ischemia via jugular vein. Extensive
      formation of DNA strand breaks, the typical biochemical feature of apoptosis, was
      detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated
      d UTP-biotin nick and labeling (TUNEL) method. Also, cysteine aspartate specific
      proteinase (caspase)-3 and caspase-9 activities a universal effector of
      apoptosis, were determined. Trunk blood was extracted to determine the serum
      contents related to oxidant-antioxidant status. In hemodynamic parameters, there
      was no significant difference in HR or BP values among any group. CAPE
      administration had no a significant effect on hemodynamic parameters during
      ischemia or reperfusion. Control group revealed extensive TUNEL-positive
      cardiomyocytes especially in free wall of left ventricule, interventiculare
      septum and nearly apex zone. Intensity of TUNEL-positive cardiomyocytes reduced
      as a result of CAPE treatment compared to control group in the same sections.
      Result of the caspase activities was found to correlate with TUNEL evaluation.
      CAPE also, ameliorated antioxidant status. We propose that CAPE acts in the heart
      as a potent scavenger of free radicals to prevent the apoptotic effect of I/R.
      Further studies are needed to elucidate the mechanisms of apoptotic death
      machinery.

PMID- 15725510
TI  - Oral exposure to atrazine modulates cell-mediated immune function and decreases
      host resistance to the B16F10 tumor model in female B6C3F1 mice.
AB  - Atrazine (ATZ) is used throughout North America to control annual broadleaf weeds
      and grasses in various crops including; corn, sorghum, and sugar cane.
      Unfortunately, contamination of surface and ground water has occurred as a result
      of ATZ's chemical and physical properties, and its widespread use throughout the
      U.S. Midwest. A study of ATZ's immunomodulatory properties was conducted using
      female B6C3F1 mice and a panel of immune assays and host resistance models
      designed to evaluate cell-mediated and antibody-mediated immunity. Mice were
      administered ATZ by gavage (0, 24, 250, and 500 mg/kg/day) for 14 days then
      evaluated for immune responsiveness. ATZ treatment significantly increased the
      number of splenic CD8+ T cells, cytotoxic T cell and mixed leukocyte responses,
      and dose-dependently reduced host resistance to B16F10 melanoma. Thymus and
      spleen weights, total spleen cell numbers and fixed macrophage function was also
      reduced in mice that were exposed to ATZ. These results demonstrate that oral ATZ
      exposure is sufficient to alter cell-mediated immune function and disease
      resistance in female B6C3F1 mice.

PMID- 15725512
TI  - Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats. The
      effects of vitamin E and catechin.
AB  - Doxorubicin (DXR) is an anthracycline antibiotic, broadly used in tumor therapy.
      In the present study we investigated whether vitamin E and catechin can reduce
      the toxic effects of doxorubicin. Vitamin E (200 IU/kg/week), catechin (200
      mg/kg/week), doxorubicin (5 mg/kg/week), doxorubicin+vitamin E (200 IU/kg/week),
      doxorubicin+catechin (200 mg/kg/week) combinations were given to rats weighing
      210-230 g (n=6/group). Changes in major enzymes participating in free radical
      metabolism superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSHPx),
      catalase (CAT) and malondialdehyde (MDA) were evaluated in the livers of all
      animals. Superoxide dismutase and catalase activity increased in the doxorubicin
      treated group compared to control (P<0.05). Glutathione peroxidase levels
      increased in the catechin+doxorubicin-treated group (P<0.05) and reached maximum
      concentrations in the doxorubicin-treated group compared to control (P<0.01).
      Malondialdehyde levels increased in the doxorubicin-treated group compared to
      control and all-treated groups (P<0.05). Malondialdehyde, glutathione peroxidase
      and catalase activities were decreased in the vitamin E+doxorubicin- and
      catechin+doxorubicin-treated group compared to doxorubicin-treated group
      (P<0.05). All enzymes activities showed no statistical differences in the not
      mentioned groups above (P>0.05). Electron microscopic studies supported
      biochemical findings. We conclude that vitamin E and catechin significantly
      reduce doxorubicin-induced hepatotoxicity in rats.

PMID- 15725511
TI  - Hematological changes in rats chronically exposed to oral aluminum.
AB  - This study was aimed to investigate the effects of the long-term oral exposure to
      aluminum sulfate on hematological parameters in rats. For this purpose, 24 adult
      female Wistar rats were divided in three groups with 8 animals each (control,
      citrate, and citrate plus aluminum groups). Rats from control and citrate groups
      had free access to tap water and to a sodium citrate solution (35 mM),
      respectively. Rats from citrate plus aluminum group received, as unique source of
      liquid, an aluminum sulfate solution (30 mM) diluted in the above-mentioned
      sodium citrate solution, ad libitum. After the treatment period (18 months),
      aluminum-exposed rats showed a significant decrease in the number of red blood
      cells, blood hemoglobin concentration and hematocrit when compared to rats from
      the control group. Serum iron levels were also significantly lower in citrate
      plus aluminum group, whereas total iron binding capacity did not change after
      citrate plus aluminum exposure. Erythrocyte thiobarbituric acid-reactive
      substances (TBARS) and nonprotein thiols (NPSH) levels, erythrocyte osmotic
      fragility and hepatic delta-aminolevulinic acid dehydratase (delta-ALA-D)
      activity did not change after treatment with citrate plus aluminum. Conversely,
      aluminum exposure increased delta-ALA-D activity in bone marrow. The present
      results indicate that long-term oral exposure to low doses of aluminum sulfate
      promotes alterations on erythrocyte parameters in rats, probably as a consequence
      of alterations in the iron status. In addition, although the details of the
      underlying mechanism remain unclear, our study reports, for the first time, a
      stimulatory effect of chronic aluminum exposure on bone marrow delta-ALA-D
      activity.

PMID- 15725513
TI  - Effects of in utero and lactational exposure to flutamide in SD rats: comparison
      of the effects of administration periods.
AB  - Pregnant CD(SD) IGS rats were given flutamide (FLUT) orally at doses of 0.4, 2,
      or 10 mg/kg/day from gestational day 6 to postnatal day (PND) 20, and the effects
      of FLUT exposure on male offspring were examined 10 weeks after birth, and
      compared to the effects in offspring treated after weaning and in offspring
      untreated after weaning. Although the body weight of the dams treated with FLUT
      remained normal, two dams in the 10 mg/kg/day group were killed because of
      abnormal parturition periods and loss of all the pups. The number of stillborns
      and dead newborns at birth was significantly higher in the 10 mg/kg/day group
      than in the control groups. No abnormalities in the reproductive parameters of
      the other dams treated with FLUT were detected. The body weights of the male
      offspring in each group remained normal from birth until the end of the study.
      The ano-genital distance was significantly shortened in 2 and 10 mg/kg/day
      groups. Changes in the organ weights and gross findings were detected in the 2
      and/or 10 mg/kg/day groups with or without the continuous administration of FLUT
      after weaning; these changes were more appreciable in groups treated with FLUT
      after weaning than in groups untreated after weaning. The prolongation of
      preputial separation was observed in the 0.4 and 2 mg/kg/day groups treated with
      FLUT after weaning, but this change was not detected in the same dose groups
      untreated after weaning. The testosterone levels were higher in the 10 mg/kg/day
      group treated with FLUT after weaning. The present data demonstrated that the
      endocrine-mediated effects on rats were more appreciable in offspring treated
      with FLUT after weaning than in offspring untreated after weaning.

PMID- 15725514
TI  - Cytotoxicity of trichloroethylene and perchloroethylene on normal human epidermal
      keratinocytes and protective role of vitamin E.
AB  - Trichloroethylene (TCE) and perchloroethylene (PERC), the most common alkenyl
      halides, have been extensively used in industry, and can cause skin damage. To
      evaluate their cytotoxic potential on skin, the effects of these agents on the
      normal human epidermal keratinocytes (NHEK) were investigated. Their action on
      cell viability, membrane integrity and lipid peroxidation (LPO) was assessed by
      neutral red uptake (NRU) assay, lactate dehydrogenase (LDH) release test and
      measurement of malondialdehyde (MDA) levels and superoxide dismutase (SOD)
      activity. In addition, the protective effect of antioxidatant vitamin E on the
      cytotoxicity was also studied. Incubation of NHEK with various concentrations
      (0.01-31.6 mM) of TCE or PERC caused a dose-dependent decrease in cell viability,
      with 80% reduction at 31.6 mM. NR50 values from the cytotoxicity assay was found
      to be 4.53 and 2.16 mM for TCE and PERC, respectively. A time- and concentration-
      dependent release of LDH were observed at 1, 2, 3, 4 h after cells were exposed
      to different doses of TCE or PERC. These agents also caused an increase of MDA,
      whilst an inhibition of SOD activity, in a concentration-dependent manner. Pre
      treatment of the cells with vitamin E at 10-200 mM dose-dependently attenuated
      the cytotoxic effect of TCE or PERC. Pre-treatment with vitamin E also reversed
      subsequent TCE or PERC-induced release of LDH, elevation of lipid peroxidation
      and decline of anti-oxidant enzyme activities. These results suggest that TCE and
      PERC could induce cytotoxicity to NHEK associated with oxidative stress and
      antioxidatant vitamin E could effectively protect NHEK from TCE- or PERC-induced
      cytotoxicity, which may be associated to the superoxide scavenging effect and
      enhancement of anti-oxidant enzyme activities.

PMID- 15725515
TI  - Comparison of para-aminophenol cytotoxicity in rat renal epithelial cells and
      hepatocytes.
AB  - Several chemicals, including para-aminophenol (PAP), produce kidney damage in the
      absence of hepatic damage. Selective nephrotoxicity may be related to the ability
      of the kidney to reabsorb filtered water, thereby raising the intraluminal
      concentration of toxicants and exposing tubular epithelial cells to higher
      concentrations than would be present in other tissues. The present experiments
      tested the hypothesis that hepatocytes and renal epithelial cells exposed to
      equivalent concentrations of PAP would be equally susceptible to toxicity.
      Hepatocytes and renal epithelial cells were prepared by collagenase digestion of
      tissues obtained from female Sprague-Dawley rats. Toxicity was monitored using
      trypan blue exclusion, oxygen consumption and ATP content. We measured the rate
      of PAP clearance and formation of PAP-glutathione conjugate by HPLC. We found
      that renal epithelial cells accumulated trypan blue and showed declines in oxygen
      consumption and ATP content at significantly lower concentrations of PAP and at
      earlier time points than hepatocytes. The half-life of PAP in hepatocyte
      incubations was significantly shorter (0.71+/-0.07 h) than in renal epithelial
      cell incubations (1.33+/-0.23 h), suggesting that renal epithelial cells were
      exposed to PAP for longer time periods than hepatocytes. Renal epithelial cells
      formed significantly less glutathione conjugates of PAP (PAP-SG) than did
      hepatocytes, consistent with less efficient detoxification of reactive PAP
      intermediates by renal epithelial cells. Finally, hepatocytes contained
      significant more reduced glutathione (NPSH) than did renal epithelial cells,
      possibly explaining the enhanced formation of PAP-SG by this cell population. In
      conclusion, our data indicates that renal epithelial cells are intrinsically more
      susceptible to PAP cytotoxicity than are hepatocytes. This enhanced cytotoxicity
      may be due to longer exposure to PAP and/or reduced detoxification of reactive
      intermediates due to lower concentrations of reduced NPSH in renal epithelial
      cells than in hepatocytes.

PMID- 15725516
TI  - Dose-dependent allergic responses to an extract of Penicillium chrysogenum in
      BALB/c mice.
AB  - Indoor mold has been associated with the development of allergic asthma.
      Penicillium chrysogenum, a common indoor mold, is known to have several allergens
      and can induce allergic responses in a mouse model of allergic penicilliosis. Our
      hypothesis is that soluble components of P. chrysogenum (PCE) can dose
      dependently induce responses typical of allergic asthma in BALB/c mice. Mice were
      exposed to 10, 20, 50, or 70 microg of PCE by involuntary aspiration four times
      over a 4-week period. Serum and bronchoalveolar lavage fluid (BALF) were
      collected before (day 0), and at days 1 and 3 following the final exposure. PCE
      exposed mice demonstrated dose-dependent increases in: BALF total cell numbers
      including eosinophil, serum and BALF total IgE levels, BALF IL-5 levels, and
      increased severity of histopathologic lesions. A single exposure to the highest
      dose of PCE resulted in edema and cellular damage but not immune responses. Four
      exposures to Metarhizium anisopliae crude antigen (10 microg, positive control)
      resulted in equivalent or greater allergic asthma-like responses than those
      demonstrated by multiple exposures to 50 or 70 microg of PCE. Multiple exposures
      to 70 microg of PCE showed increased allergen-triggered immediate respiratory
      responses as well as non-specific airway hyperresponsiveness to methacholine as
      assessed by barometric whole-body plethysmography. Taken together, repeated
      pulmonary challenge with P. chrysogenum extract induced dose-dependent allergic
      asthma-like responses in mice.

PMID- 15725518
TI  - Fluoride metabolism and fluorosis.
AB  - OBJECTIVES: This paper is primarily concerned with the only proven risk
      associated with water fluoridation: enamel fluorosis. Its purpose is to review
      current methods of measuring enamel fluorosis, its aetiology and metabolism. A
      further objective is to identify risk factors to reduce the prevalence of enamel
      fluorosis and employ methods to manage such risk factors. DATA: The prevalence of
      enamel fluorosis is increasing in Ireland and internationally. A critical period
      has been identified at which teeth are most at risk of developing enamel
      fluorosis: 15-24 months of age for males and 21-30 months of age for females. The
      data included took these two factors into account. SOURCE: A thorough narrative
      review of published literature was conducted to identify studies concerning the
      aetiology and metabolism of enamel fluorosis. Risk factors for fluorosis were
      identified from these studies. STUDY SELECTION: As it is the pre-eruptive phase
      of enamel development which represents the greatest risk to developing enamel
      fluorosis, studies examining sources of fluoride ingestion for young children
      were selected. These included studies on ingestion of fluoride toothpaste by
      young children, fluoride supplementation and infant formula reconstituted with
      fluoridated water. CONCLUSIONS: There is evidence that the age at which tooth
      brushing with fluoride toothpastes is commenced and the amount of fluoride placed
      on the brush are important risk factors in the incidence of dental fluorosis. It
      is recommended that brushing should not commence until the age of 2 and that a
      pea-sized amount (0.25 g) of toothpaste should be placed on the brush.

PMID- 15725519
TI  - Caries and fluoride processes.
AB  - OBJECTIVES: The purpose of the work was to establish the level and source of
      salivary fluoride, whether it could interact with tooth mineral and whether it
      was able to effect calcium re-acquisition and remineralisation. METHODS: Fluoride
      in saliva and in solution was measured by electrode, calcium by complexometric
      titration and phosphate colourimetrically-to measure salivary fluoride, its
      uptake by mineral and the effects of such low levels on calcium and phosphate
      levels in solution in contact with suspensions of mineral hydroxyapatite.
      RESULTS: Fluoride levels in saliva were low but could interact with
      hydroxyapatite. Such levels caused apatite crystallite growth and preferential
      acquisition of calcium by calcium-deficient apatite. CONCLUSIONS: Salivary
      fluoride contents rose with increasing water fluoride levels. It was acquired by
      hydroxyapatite mineral. Topical fluoride was stored on oral tissues. Even these
      low fluoride contents could cause mineral crystallite growth with preferential
      calcium uptake. On a mineral area basis these effects were caused by quite low
      fluoride uptakes. These findings do not support reliance upon large fluoride
      uptakes by tooth enamel as evidence for commensurate caries reductions.

PMID- 15725520
TI  - Quantification of dental plaque in the research environment.
AB  - OBJECTIVES: To review the established and novel methods of plaque quantification
      employed in dental research, including a discussion of their merits and to
      present a new method of planimetrically measuring plaque using light induced
      fluorescence. METHOD: Quantitative light-fluorescence (QLF) images were acquired
      from the buccal surfaces of an individual who had refrained from oral hygiene
      both with and without traditional plaque disclosure. Digital photographs were
      also taken. Images were analysed using a novel method and a percentage plaque
      index produced. RESULTS: Traditional plaque indices are problematic due to their
      integral nature and their failure to detect small, but potentially clinically
      relevant changes in plaque area. The use of a fluorescent technique demonstrated
      good reliability although there was no correlation between red fluorescent plaque
      and total disclosed plaque suggesting that the auto-fluorescing plaque is not a
      good measure of total plaque volume. CONCLUSIONS: The use of planimetric
      techniques can increase the power of plaque studies, potentially reducing the
      number of subjects and time required to separate therapies or products.
      Fluorescent methods of quantification have potential as they enable clear
      separation of the plaque covered and non-covered tooth surfaces.

PMID- 15725521
TI  - Developments in dental plaque pH modelling.
AB  - OBJECTIVES: The objectives of this review were to give a comprehensive account of
      the methods used to determine dental plaque pH over the last 50 years, to review
      how these methods have been used in dental cariology research and to give an
      update as to how dental plaque pH studies might be developed in the future. DATA:
      Published, referred papers and abstracts of conference proceedings in the
      literature were reviewed. SOURCES: A comprehensive search of the electronic
      databases PubMed and Medline, was undertaken. In addition, a hand search of the
      Index Denticus was done to identify relevant citations before 1966. STUDY
      SELECTION: Relevant published literature in peer-reviewed publications was
      reviewed. No additional inclusion criteria were applied. CONCLUSIONS: This
      comprehensive review gives an account of the background to, history of, relative
      merits and demerits of, applications of and future of dental plaque pH
      technologies.

PMID- 15725522
TI  - Health benefits of saliva: a review.
AB  - OBJECTIVE: The aim is to present a review of the literature on human saliva
      composition, flow rates and some of the health benefits of saliva, with emphasis
      on studies from our laboratory that have looked at effects of age and age-related
      diseases on saliva output and composition. DATA: Saliva influences oral health
      both through its non-specific physico-chemical properties, as well as through
      more specific effects. The proline-rich proteins, statherin and the histatins are
      salivary proteins that influence calcium phosphate chemistry, initial plaque
      formation and candida infection. Increases or decreases in mastication may affect
      saliva output. Our cross-sectional studies of saliva in a large population-based
      study cohort (N=1130) indicate that there is an age-related decline in saliva
      output for unstimulated whole, stimulated parotid, unstimulated
      submandibular/sublingual and stimulated submandibular/sublingual saliva, as well
      as some compositional alterations in anti-microbial and other proteins. Some of
      these alterations also appear to be specific for certain age-related medical
      conditions, such as diabetes mellitus. CONCLUSIONS: These studies and data
      presented confirm the importance of saliva in maintaining a healthy oral
      environment; the practitioner is encouraged to consider saliva output and medical
      conditions that may compromise it as part of routine dental treatment planning.

PMID- 15725523
TI  - The use of in situ models and QLF for the study of coronal caries.
AB  - OBJECTIVES: The purpose of the paper is to review aspects of the systems
      available to model the caries process in enamel. METHODS: The in situ model
      developed in Liverpool, and the new method of quantifying mineral loss,
      Quantitative Light-induced Fluorescence (QLF), are described. QLF is a powerful
      new diagnostic tool which can be used to measure demineralisation and
      remineralisation in tooth surfaces in vivo; studies to optimise, validate and use
      QLF in different clinical situations are described. RESULTS: Examples of the use
      of in situ models show that they are particularly valuable for monitoring de and
      remineralisation of artificial lesions in relation to product testing as
      alternatives to clinical trials, and present significant advances over in vitro
      methods. Quantification of mineral loss by Transverse Microradiography (TMR) as
      in the traditional Liverpool model has produced much valuable information, but
      the destructive nature of the method limits experimental design, and removes the
      system from the clinical situation. As a possible alternative, QLF has been
      validated and optimised. Longitudinal measures can be made on the same surface,
      and examples of its use are for monitoring recurrent caries and demineralisation
      around orthodontic brackets. CONCLUSIONS: While current in situ models provide a
      major advance over earlier caries models, measurement of de and remineralisation
      by destructive methods such as transverse microradiography limits the design of
      experimental investigations. QLF offers significant time saving, reduces the cost
      of clinical studies, and because the measurements can be carried out
      longitudinally in vivo, can remove the need for intra-oral appliances carrying
      experimental tissues.

PMID- 15725524
TI  - Dental erosion: possible approaches to prevention and control.
AB  - OBJECTIVES: To discuss the key elements for establishment of a preventive
      programme for dental erosion. DATA AND SOURCES: The data discussed are primarily
      based on published scientific studies and reviews from case reports, clinical
      trials, epidemiological, cohort, animal, in vitro and in vivo studies. References
      have been traced manually or by MEDLINE. STUDY SELECTION: The aetiology,
      pathogenesis and modifying factors of dental erosion were reviewed. Strategies to
      either prevent the occurrence or limit the damage of dental erosion or protect
      the remaining tooth tissues from further erosive destruction were reviewed and
      discussed. These includes: (A) measures to (1) enhance remineralisation and acid
      resistance of enamel surface softened by erosive challenge, (2) reduce the
      erosive potential of acidic products, (3) enhance salivary flow, (4) protect and
      restore erosively damaged tooth, and (5) provide mechanical protection against
      erosive challenge. (B) Health education geared towards (1) diminution of
      frequency of intake of dietary acids, and (2) change of habits and lifestyles
      that predispose teeth to erosion development. CONCLUSIONS: It may be easier to
      gain patients' compliance with the advice that immediately following an acidic
      challenge, a remineralising agent, such as fluoride mouthrinses, fluoride
      tablets, fluoride lozenges or dairy milk, should be administered to enhance rapid
      remineralisation of the softened tooth surface as well as serve as a mouth
      refresher, or an alternative, a neutralising solution should be used. Effective
      counselling on erosion preventive regimes should involve all healthcare
      personnel, dentists, doctors, pharmacist, nurses/hygienists and clinical
      psychologists.

PMID- 15725525
TI  - Development of an in situ root caries model. A. In vitro investigations.
AB  - OBJECTIVES: The paper describes preliminary in vitro investigations, the
      objectives of which were to examine the influence of certain experimental
      parameters on artificial carious lesion formation in root hard tissues, and their
      remineralisation. These experiments formed part of a wider study that aimed to
      develop an in situ model of root caries, based on the existing coronal caries
      model used in Liverpool. The present studies examined the effects (a) of the
      anatomical origin of the dentine, the presence or absence of cementum, the
      exposure time and the type of demineralising system, on lesion development, and
      (b) of baseline lesion size on the extent and location of mineral re
      precipitation. METHODS: Mineral content parameters in plano-parallel sections
      taken from dentine lesions were determined by computer-controlled transverse
      microradiography. RESULTS: The importance of the anatomical origin of the dentine
      on lesion formation was investigated by comparing in vitro lesion formation in
      premolar and molar dentine, and in dentine from apical, middle and coronal thirds
      of the root: no difference was observed between these sites. Lesions formed more
      rapidly in acid buffer solutions than in acid gel systems, and were more reliably
      produced when cementum was removed. The effect of baseline lesion size on
      subsequent in vitro remineralisation demonstrated that a small baseline mineral
      content was associated with a larger percentage mineral gain. The location of
      mineral deposition throughout the lesion was also influenced by baseline mineral
      content parameters. CONCLUSIONS: The results form a basis for the further
      development of an in situ dentinal caries model, providing data to suggest that
      manipulation of parameters involved in the preparation of artificial carious
      lesions has a significant effect on the behaviour of the lesion, particularly the
      phenomenon of remineralisation. Further work is needed to investigate the
      behaviour of the model in situ.

PMID- 15725526
TI  - Development of an in situ root caries model B. In situ investigations.
AB  - OBJECTIVES: The aims of this pilot study were to assess the suitability of an in
      situ model for root caries studies, and to investigate the effect of sub-surface
      lesion mineral content and ultrastructural organisation on remineralisation.
      METHODS: Subjects were selected by criteria generally used for coronal caries
      models. Plaque pH responses and salivary flow rates were determined by standard
      methods. The chosen substrate was human dentine with artificially induced caries
      like demineralisation and sterilised by gamma-irradiation (4100 Gy). Two levels
      of baseline demineralisation were induced by exposure to an acid buffer for 2 or
      5 days. Mineral content was measured by computer-controlled quantitative
      microradiography. RESULTS: Remineralisation in situ was greater in smaller
      lesions with lower surface mineral content than in larger lesions in which the
      surface mineral content was high. CONCLUSIONS: The model is suitable for further
      development for investigating dentinal caries. More work is needed to validate
      the model by means of a fluoride dose-response study.

PMID- 15725527
TI  - Implications of the re-invasion of Southeast Uganda by Glossina pallidipes on the
      epidemiology of bovine trypanosomosis.
AB  - A study to assess the influence of re-invasion of Glossina pallidipes on the
      epidemiology of bovine trypanosomosis was conducted in Southeast Uganda. A total
      of 1,992 cattle were screened in villages, with (949) and without G. pallidipes
      (1043) for trypanosomosis using a combination of the BCT and HCT methods. The
      prevalence of trypanosomosis (15.5%), Trypanosoma brucei infection (1.4%), T.
      congolense infection (7.2%), T. vivax infection (5.3%) and mixed infection (1.6%)
      in cattle in villages with was significantly higher than in those without G.
      pallidipes: trypanosomosis (7.1%), T. brucei infection (0.6%), T. congolense
      infection (2.0%), T. vivax infection (3.3%) and mixed infection (1.2%) (overall
      trypanosome infection, chi2=35.5, d.f.=1, P<0.05; T. brucei infection, chi2=8.06,
      d.f.=1, P<0.05; T. congolense infection, chi2=22.8, d.f.=1, P<0.05 and T. vivax
      infection, chi2=6.4, d.f.=1, P<0.05). Infections of Trypanosoma congolense were
      predominant in cattle in villages with G. pallidipes, while T. vivax infections
      were predominant in cattle in villages without. In all villages, T. brucei
      infections were fewer than either T. congolense or T. vivax infections. The risk
      of transmission of T. brucei, T. congolense and T. vivax infections was 3, 2.7
      and 1.6 times, respectively, higher in villages with G. pallidipes than in those
      without, despite the presence of G. f. fuscipes in either set of villages. The
      mean PCV (28.27+/-0.41, 95% CI) and mean herd size (3+/-0.46) of cattle in
      villages with G. pallidipes were significantly (P<0.05) lower than in those in
      villages without (mean PCV, 29.48+/-0.34; mean herd size, 4+/-0.72). It is
      evident that presence of G. pallidipes brings about an increase in the prevalence
      of T. congolense, which causes a more severe disease in cattle than other species
      of trypanosomes. This is a rare case of a re-invasion of a tsetse species whose
      disease transmission capability calls for refocusing of the traditional national
      tsetse and trypanosomosis control strategies to contain it.

PMID- 15725528
TI  - Cryptic species within the Tetratrichomonas gallinarum species complex revealed
      by molecular polymorphism.
AB  - Tetratrichomonas gallinarum is a widespread intestinal parasite of galliform and
      anseriform birds. The pathogenicity of this species is controversial, presenting
      an unsettled problem as yet. We analysed the polymorphism and genetic
      relationship among 29 isolates of T. gallinarum obtained from eight bird species
      and five T. gallinarum-like isolates from the oral cavity and lower respiratory
      tract of human patients. Two methods were used for the analyses: RAPD and
      sequencing of 16S rRNA, 5.8S rRNA, ITS1 and ITS2 genes, both producing consistent
      and well-supported results. The isolates were divided into five groups, A-E, with
      eleven subgroups. The distance between groups E, D and the cluster A-B-C
      considerably exceeded usual intraspecific polymorphism seen in trichomonads.
      Moreover, the largest subgroup, A2 (containing 18 isolates), was divided into
      three branches according to the host specificity. All isolates from humans were
      placed into avian subgroups A2 and B2. We conclude that our isolates represent,
      at least, three morphospecies or rather complexes of several cryptic species.
      Since certain species of the T. gallinarum complex can differ in their biological
      characteristics and some of them can infect humans, the problem of T. gallinarum
      pathogenicity should be re-examined with regard to specific genetic groups and
      zoonotic potential of some of these lineages should be considered.

PMID- 15725529
TI  - Production of antibodies in murine mucosal immunization with Toxoplasma gondii
      excreted/secreted antigens.
AB  - Toxoplasmagondii RH strain excreted/secreted antigens (ESA) were administrated
      weekly by the oral route, to two groups of 40 OF1 mice for 4 weeks. One group
      received ESA associated with cholera toxin (CT+) and the other, ESA only (CT-).
      Five animals from each group were sacrificed from day 4 (D4) to D49 following the
      first immunization and their feces and sera were collected and tested by ELISA
      for IgA, IgG and IgM antibody detection. In feces, IgA antibodies were detected
      on D4 and on D12 in the CT+ and CT- groups, respectively, and they persisted up
      to D49. IgG antibodies were detected from D12 to D41 in the CT+ group and on D12
      only in the CT- group. No IgM antibodies were detected. In sera, IgA antibodies
      were detected on D27, D41 and D49 only in the CT+ group. IgG and IgM antibodies
      were found on D12 and D4, respectively, in the CT+ group and starting from D27 in
      the CT- group. To our knowledge, this is the first demonstration that ESA, with
      or without CT, are immunogenic when administrated by the oral route.

PMID- 15725530
TI  - The modulatory influence of Trypanosoma brucei on challenge infection with
      Haemonchus contortus in Nigerian West African Dwarf goats segregated into weak
      and strong responders to the nematode.
AB  - Although Nigerian West African Dwarf (WAD) goats are relatively resistant to
      infection with Haemonchus contortus and are also trypanotolerant, natural
      outbreaks of both infections are known to occur. Despite their relative
      resistance to H. contortus WAD goats nevertheless show variability in response
      phenotype and it was of interest to examine the effect of this variability on the
      outcome of concurrent trypanosome infection. Trypanosoma brucei infections were
      established in goats that were initially classified as good or poor responders to
      H. contortus. Thirty-nine goats were exposed to an escalating infection with H.
      contortus, and on the basis of their mean faecal egg counts (FEC) were allocated
      to high FEC (poor responders, 18 goats with the highest FEC) or low FEC (good
      responders, 18 goats with the lowest FEC) classes. Nine uninfected naive control
      goats were included to provide reference baseline values. Retrospective analysis
      of parasitological and pathological parameters after allocation into high/low FEC
      classes showed that FECs differed significantly, in both classes packed cell
      volume (PCV) values fell relative to naive controls, neither class lost weight
      and both generated marked IgG responses. All goats received anthelmintic on day
      61, half of each group was infected with 50 million trypanosomes and on day 67,
      excepting the controls, all goats were challenged with 3000 L3 of H. contortus.
      Trypanosome parasitaemia was generally low, and marginally, but not
      significantly, higher in the low compared with high FEC class, peaking 12-16 days
      after exposure in both groups and then falling to below microscopically
      detectable levels (although still detectable by sub-inoculation into mice) by
      week 3. At autopsy (days 109/110), worm burdens were significantly higher in the
      trypanosome-infected goats from the high FEC class, relative to all other groups.
      Trypanosome infected goats showed a tendency (although not significant) towards
      higher FEC and, irrespective of their FEC class, had lower PCV values although
      body weight did not vary significantly. All goats challenged with H. contortus
      had higher antibody levels than naive controls, but neither trypanosome infection
      nor FEC class affected the magnitude of responses. These results confirm that WAD
      goats comprise a range of response phenotypes to initial H. contortus infection
      and that trypanotolerance is a key trait of this breed. Although immunity to
      nematode infection develops even in poor responders, these animals harbour higher
      nematode burdens during concurrent infection with T. brucei.

PMID- 15725531
TI  - Feline leishmaniasis due to Leishmania (Leishmania) amazonensis in Mato Grosso do
      Sul State, Brazil.
AB  - A case of leishmaniasis in a domestic cat (Felis domesticus) is described. The
      animal showed a single, nodular lesion on the nose and many nodules of different
      size on the ears and digital regions of all the paws. Diagnosis was made by
      microscopic detection of amastigotes in Giemsa-stained smears from the lesions.
      By monoclonal antibodies the aetiological agent was identified as Leishmania
      (Leishmania) amazonensis, one of the seven species implicated in human
      leishmaniasis in Brazil. The clinical signs in feline leishmaniasis are
      unspecific and similar to those observed in other diseases such as cryptococcosis
      and in sporotrichosis, commonly found in cats. Leishmaniasis should therefore, be
      added to the differential diagnosis by feline veterinary practitioners and
      adequate investigations should carried out for dermal leishmaniasis in the area
      where the feline infection is detected.

PMID- 15725532
TI  - Cross-reactivities with Cryptosporidium spp. by chicken monoclonal antibodies
      that recognize avian Eimeria spp.
AB  - In a previous study, we have developed several chicken monoclonal antibodies
      (mAbs) against Eimeria acervulina (EA) in order to identify potential ligand
      molecules of Eimeria. One of these mAbs, 6D-12-G10, was found to recognize a
      conoid antigen of EA sporozoites and significantly inhibited the sporozoite
      invasions of host T lymphocytes in vitro. Furthermore, some of these chicken mAbs
      showed cross-reactivities with several different avian Eimeria spp. and the mAb
      6D-12-G10 also demonstrated cross-reactivities with the tachyzoites of Neospora
      caninum and Toxoplasma gondii. Cryptosporidium spp. are coccidian parasites
      closely related to Eimeria spp., and especially C. parvum is an important cause
      of diarrhea in human and mammals. In the present study, to assess that the
      epitopes recognized by these chicken mAbs could exist on Cryptosporidium
      parasites, we examined the cross-reactivity of these mAbs with Cryptosporidium
      spp. using an indirect immunofluorescent assay (IFA) and Western blotting
      analyses. In IFA by chicken mAbs, the mAb 6D-12-G10 only showed a
      immunofluorescence staining at the apical end of sporozoites of C. parvum and C.
      muris, and merozoites of C. parvum. Western blotting analyses revealed that the
      mAb 6D-12-G10 reacted with the 48-kDa molecular weight band of C. parvum and C.
      muris oocyst antigens, 5D-11 reacted the 155 kDa of C. muris. Furthermore, these
      epitopes appeared to be periodate insensitive. These results indicate that the
      target antigen recognized by these chicken mAbs might have a shared epitope,
      which is present on the apical complex of apicomplexan parasites.

PMID- 15725533
TI  - Inter and intra-specific genetic variation of avian Eimeria isolated from Iran by
      random amplified polymorphic DNA--polymerase chain reaction.
AB  - Eimeria species from poultry breeder farms without previous exposure to
      anticoccidial vaccines in five distinct geographical regions of Iran were
      examined for genetic relatedness by the random amplified polymorphic DNA (RAPD)
      assay. Eight different oligonucleotide decamers with arbitrary DNA sequences were
      tested as primers to amplify DNA from five isolates of each E. acervulina, E.
      tenella, and E. maxima. Depending on the species/isolate-primer combination,
      between 1 and 14 DNA fragments ranging in size from 240 to 3000 bp were
      amplified. The two isolates originated from Northeast and North parts of Iran
      showed minor differences and two isolates originated from Northeast and Southwest
      of Iran showed major differences in their amplified DNA patterns. The intra
      specific similarity coefficient within five isolates of each species of, E.
      acervulina, E. tenella, E. maxima was 74, 82 and 72%, respectively. The distance
      indices observed between species were greater than those found between isolates
      (80-90%) with all examined primers. The inferred phylogenetic tree on the
      fingerprinting of all species revealed that the RAPD-PCR can easily differentiate
      within and between species and could be a useful and valuable tool in future
      epidemiological studies, designing and developing of vaccines against avian
      coccidosis, here in Iran and neighboring countries.

PMID- 15725534
TI  - Field evaluation of an intravital diagnostic test of Echinococcus multilocularis
      infection in red foxes.
AB  - Echinococcus multilocularis parasitizes the small intestine of red foxes (Vulpes
      vulpes) and other carnivores, and has a wide distribution throughout the northern
      hemisphere. This cestode is the causative agent of human alveolar echinococcosis,
      a life-threatening helminth zoonosis. In 2000-2002, 2130 red foxes were examined
      for its presence in Slovakia, with a total prevalence of 30.7%. The data on
      occurrence were obtained by the combination of necropsy of small intestines from
      red foxes and coproantigen detection in faecal samples. The correlation between
      the number of detected specimens and the value of optical density of copro-ELISA
      test was found. When worm burdens were low (1-25 specimens) the sensitivity of
      the method was 31.3+/-8.64%, when worm burdens were >50 specimens, 81.8+/-0.66%,
      and with high worm burdens (>1000 specimens) the sensitivity reached 100+/-0.34%.
      E. multilocularis presence was detected using the nested PCR method from the eggs
      in the faecal samples with a 100% specificity. In epidemiological surveys of this
      zoonosis, it is of crucial importance to detect animals with a high level of
      infection, which are responsible for the bulk of environmental contamination. The
      advantage of copro-ELISA test lies in allowing the intravital diagnostics to be
      employed within the epidemiological survey of E. multilocularis occurrence in the
      protected and urban areas.

PMID- 15725535
TI  - Diagnosis of cystic echinococcosis on sheep farms in the south of Argentina:
      areas with a control program.
AB  - In 2000 Guarnera et al. proposed using ELISA in canine faeces collected from the
      ground to detect dogs infected with Echinococcus granulosus, thus determining
      sheep farms with active transmission. The objective was to evaluate the
      prevalence of E. granulosus infection in sheep farms of the Patagonia. Sheep
      farms were randomly selected in the Provinces of Rio Negro, Chubut, Neuquen,
      Santa Cruz and Tierra del Fuego (areas with control programs) and La Pampa
      (comparison area). From one to three samples of fecal matter were obtained for
      each sheep farm, which were processed by means of copro-ELISA test with
      confirmation of positive samples by copro-Western blot. A total of 1042 samples
      were obtained from 352 sheep farms, 26 (7.3%) proving positive. Of these 5 (6.3%)
      were from La Pampa, 9 (13.8%) from Neuquen, 4 (4.7%) from Rio Negro, 2 (2.9%)
      from Chubut, 1 (5.9%) from Santa Cruz and 5 (13.9%) from Tierra del Fuego. The
      identification of parasitized dogs is an essential activity upon which rests the
      strategy of control and surveillance. Arecoline tests or coproantigen test with
      fecal matter obtained directly from the dog contribute information on individual
      prevalence, while the use of coproantigens detected in ground-collected samples
      transfers the dog unit of observation to units of greater epidemiological value.
      In the present experience, the technique employed seems promising for its
      application in systems of epidemiological surveillance of cystic echinococcosis
      and in drawing a baseline on which to measure the progress of control programs in
      the Argentine Patagonia in subsequent years.

PMID- 15725536
TI  - Characterization of moxidectin resistant Trichostrongylus colubriformis and
      Haemonchus contortus.
AB  - The development of moxidectin resistance (MOX-R) in sheep parasitic
      gastrointestinal nematodes already carrying multiple resistances to other
      anthelmintic groups has made control of these strains very difficult. The
      anthelmintic resistance patterns of MOX-R strains of Trichostrongylus
      colubriformis and Haemonchus contortus were characterized to provide an insight
      into the remaining role of anthelmintics in the control of such strains.
      Homozygous MOX-R individuals of both genera were unaffected by moxidectin. For
      MOX-R heterozygotes a dose rate of 200 microg/kg abamectin (ABA) given orally
      removed 25% of H. contortus while 200 microg/kg MOX given orally achieved a 72%
      reduction. Doubling the dose rate of ABA improved the mean efficacy to 37%.
      Consequently, in H. contortus, the degree of dominance differs markedly between
      the two anthelmintics. A dose rate of 8 mg/kg levamisole and 185 mg/kg
      napthalophos achieved >95% reduction in worm count of the MOX-R homozygous H.
      contortus but only 85 and 7%, respectively against the MOX-R homozygous T.
      colubriformis.

PMID- 15725537
TI  - First record of Trichinella pseudospiralis in the Slovak Republic found in
      domestic focus.
AB  - Infection of Trichinella spp. is widespread among wildlife in Slovakia and the
      red fox (Vulpes vulpes) is the main reservoir of Trichinella britovi. Trichinella
      spiralis has been rarely documented in sylvatic and domestic animals of this
      country. During routine examination of domestic pigs at the slaughter,
      Trichinella larvae were detected by artificial digestion in a domestic pig of a
      large-scale breeding farm in Eastern Slovakia. The parasite has been identified
      by molecular (PCR) and biochemical (allozymes) analyses and by the morphology of
      the nurse cell as the non-encapsulated species Trichinella pseudospiralis
      infecting both mammals and birds. The epidemiological investigation carried out
      at the farm level revealed the presence of the same parasite species in other
      three pigs of 192 examined (2.1%), in 3 of 14 (21.4%) examined synanthropic rats
      (Rattus norvegicus) and in a domestic cat. The farm was characterized by
      inadequate sanitary conditions, insufficient nutrition, cannibalism and the
      presence of rat population. A different profile has been observed at the
      phosphoglucomutase locus in T. pseudospiralis isolates from Slovakia in
      comparison with the T. pseudospiralis reference isolate from the Palearctic
      region. This is the first documented focus of T. pseudospiralis from Central
      Europe. The detection in domestic pigs of a non-encapsulated parasite infecting
      both mammals and birds stresses the need to avoid the use of trichinelloscopy to
      detect this infection at the slaughterhouse.

PMID- 15725538
TI  - Relationship of abomasal histology and parasite-specific immunoglobulin A with
      the resistance to Haemonchus contortus infection in three breeds of sheep.
AB  - This study was carried out to evaluate the relationship of abomasal inflammatory
      cells and parasite-specific immunoglobulin A (IgA) in mucus, with the resistance
      to Haemonchus contortus infection in three breeds of sheep naturally infected
      with gastrointestinal nematodes. The breeds were the native Santa Ines sheep, and
      the European Suffolk and Ile de France breeds. Mast cells, eosinophils and
      globule leucocytes were enumerated in abomasal mucosa. Eosinophils within the sub
      mucosa also were counted separately. Histamine concentration was estimated in
      abomasal tissue samples. Enzyme-linked immunosorbent assay was carried out in
      mucus samples to determine the level of IgA anti-H. contortus third and fifth
      instar. There were no significant differences among group means of these
      variables (P>0.05). The correlation coefficients between fecal egg counts
      (FEC)xmast cells (r=-0.490; P<0.05) and FECxeosinophils in sub-mucosa (r=-0.714;
      P<0.01) was significant in the Santa Ines sheep. In the Ile de France group, the
      correlation coefficients between globule leucocytesxFEC (r=-0.879; P<0.001) and
      histaminexworm burden (r=-0.833; P<0.01) were also significant. In the Santa Ines
      and Ile de France sheep, correlation coefficients between IgA anti-L3xworm burden
      and IgA anti-L3xFEC were negative. In general, inflammatory cells and IgA
      parasite-specific in abomasum were inversely associated with H. contortus worm
      burden and FEC indicating that they may impair parasite development or fecundity
      in the three breeds of sheep. However, similar mean values of inflammatory cells
      and IgA were found in the resistant (Santa Ines) and in the susceptible (Suffolk
      and Ile de France) breeds of sheep. The enumeration of cells by histological
      assessment does not provide information on their functional activity, which may
      be different among breeds. Thus, the effect of breed on the functional activity
      of these and other inflammatory cells is an important area for further study.

PMID- 15725539
TI  - The environmental safety of eprinomectin to earthworms.
AB  - A study was conducted to assess the environmental safety of the endectocide
      eprinomectin to the earthworm Lumbricus terrestris under conditions mimicking
      typical product use on pasture. The LC50 value of eprinomectin in artificial soil
      after 28 days of exposure is higher than the levels expected in feces from dosed
      cattle or in soil fertilized with manure from dosed cattle, which indicates a
      wide margin of safety for this compound to earthworms. However, the no-observed
      effect concentration has not been established. Therefore, the current study was
      conducted to determine whether there would be any effects on earthworms from
      feces from cattle treated with the commercial formulation of eprinomectin. Feces
      were collected rectally from grazing cattle on Day 0 before treatment and on Days
      2, 4, 7 and 14 after treatment with EPRINEX (eprinomectin) Pour-On for Beef and
      Dairy Cattle (Merial Limited) at 0.5 mg eprinomectin per kg bodyweight. Assays of
      eprinomectin B1a (the major component of eprinomectin) were 0, 0.427, 0.152,
      0.0512 and 0.00185 mg kg-1 wet weight of feces (equivalent to 0, 3.34, 1.19, 0.40
      and 0.010 mg kg-1 on a dry weight basis, respectively). No significant
      differences (p>0.05) were observed at any day post-treatment in the survival or
      behavioral effects of any worms fed post-dose feces relative to the worms fed
      control feces. All post-dose comparisons of weight changes of living earthworms
      to the control group were not significantly different (p>0.05), indicating that
      treatment of cattle with EPRINEX (eprinomectin) Pour-On for Beef and Dairy Cattle
      did not affect feeding or weight gain of the earthworms. The LC50 value and the
      results of this study establish the wide margin of safety afforded to earthworms
      by eprinomectin under typical usage conditions.

PMID- 15725540
TI  - Prevalence of fecal contamination in sandpits in public parks in Sapporo City,
      Japan.
AB  - A total of 107 sandpits in public parks in Sapporo City were examined, 9 and 73
      were contaminated with helminth eggs and fecal coliforms, respectively. Of the
      nine in which eggs were detected, eight were contaminated with Toxocara spp. and
      one with Capillaria spp. eggs. The contamination rate of sandpits of more than 30
      m2 ranged from 43 to 50%, while in those 30 m2 or less it was between 73 and 92%.
      Although helminth eggs were evenly distributed throughout all layers of the
      sandpits, fecal coliforms were localized on the sandpit surfaces. Recovered
      Toxocara eggs were identified according to their size and surface structures, and
      almost all eggs were T. cati. Based on these results, and given the inherent
      habits of cats, measures to prevent their defecation in sandpits are needed,
      especially ones of smaller size.

PMID- 15725542
TI  - Efficacy of an injectable, sustained-release formulation of moxidectin in
      preventing experimental heartworm infection in mongrel dogs challenged 12 months
      after administration.
AB  - The objective of this study was to ascertain the ability of a single subcutaneous
      injection of a sustained-release (SR) formulation of moxidectin to protect dogs
      against challenge inoculation with infective Dirofilaria immitis larvae 364 days
      after administration. Twenty four purpose-bred adult mixed-breed dogs were
      grouped into three blocks of eight based on weight and sex. Saline solution (0.9%
      NaCl) or a moxidectin SR formulation at volumes designed to deliver 0.17 or 0.27
      mg moxidectin/kg b.w. was injected subcutaneously on day 0. Throughout the post
      treatment period, injection sites of all dogs were periodically examined visually
      and by palpation. Palpable swellings were characterized as to size, consistency
      and the presence of associated pain or erythema. On day 364, each dog was
      inoculated subcutaneously with 50 D. immitis L3. On days 510 and 511, dogs were
      euthanatized, and their hearts, lungs and thoracic cavities were inspected for
      the presence of adult heartworms. number, sex and viability of recovered
      heartworms were determined. The mean number of heartworms recovered from dogs
      that had received the saline control injection was 35.7. No heartworms were
      recovered from any dog treated with either 0.17 or 0.27 mg moxidectin/kg b.w. For
      variable periods of time following treatment, small (1-4 mm diameter), firm,
      subcutaneous swellings could be palpated at the injection sites of dogs treated
      with 0.17 or 0.27 mg moxidectin/kg b.w. These swellings contracted progressively
      and eventually disappeared except for the case of one animal treated with 0.27
      mg/kg, in which the swelling persisted for the entire study period. At no time
      during the study was pain or erythema noted at the injection site of any dog, and
      no dog exhibited any adverse systemic reaction related to treatment. We conclude
      that under conditions pertaining in this study, a single subcutaneous injection
      of a moxidectin SR formulation at dosing rates of either 0.17 or 0.27 mg/kg b.w.
      can safely protect adult dogs against experimental challenge inoculation with
      infective heartworm larvae for a period of 12 months.

PMID- 15725541
TI  - Biochemical serum profiles in dogs experimentally infected with Angiostrongylus
      vasorum (Baillet, 1866).
AB  - The biochemical profiles of crossbred dogs experimentally infected with the
      parasite Angiostrongylus vasorum were studied. Two groups of five dogs were
      experimentally inoculated with 50 and 100 third stage infective larvae (L3) of A.
      vasorum per kilogram of body weight. A third group of five uninfected animals
      were used as control. Serum from these animals were used for biochemical tests to
      measure total and fractioned proteins, urea, creatinine and to determine the
      activities of aspartate (AST), alanine (ALT) aminotransferase, gamma-glutamyl
      transferase (GGT), alkaline phosphatase (PAL) and creatine kinase isoenzyme MB
      (CK-MB). The alpha-1, alpha-2 and beta-globulins fractions showed alterations
      during acute phase of the infection. No modifications were observed in the
      biochemical profiles of ALT, AST, GGT, PAL, urea and creatinine. CK-MB was shown
      to be a good early indicator of cardiac injury in dogs experimentally infected
      with A. vasorum.

PMID- 15725543
TI  - The potential risk of Dirofilaria immitis becoming established in the Czech
      Republic by imported dogs.
AB  - We examined 110 dogs, imported or born to imported females or living together
      with imported dogs in kennels, for the presence of Dirofilaria immitis, and
      assessed the climatic conditions in the Czech Republic that may promote spread of
      the disease. Relevant techniques were used to detect specific antigen, specific
      antibodies and microfilariae. The presence of antigen was detected in one
      imported dog, microfilariae were not found and antibodies were detected in 30.5%
      of the imported dogs. No heartworm was found in dogs, which did not travel
      outside of the Czech Republic. The evaluation of temperature charts showed that
      it was possible for at least one heartworm generation to develop under climatic
      conditions in the Czech Republic.

PMID- 15725544
TI  - Age-related differences of Ascaridia galli egg output and worm burden in chickens
      following a single dose infection.
AB  - Ninety white chickens (Lohmann LSL) were reared under helminth-free conditions
      and divided into five groups. Four groups were artificially infected with 250
      embryonated Ascaridia galli eggs at the age of 6, 12, 18 or 24 weeks. Ten birds
      were kept as uninfected controls. Six and 10 weeks after infection (p.i.),
      individual faecal egg counts (FEC) were performed. The birds were slaughtered
      after the second sampling and their gastrointestinal tracts were examined for the
      presence of adult A. galli. The FEC increased from the first to the second
      sampling significantly in all the infected groups. The highest increase was shown
      in the group infected at 12 weeks of age, whereas the increase in the other
      groups was relatively moderate. However, the total worm burden and mean FEC at
      the second sampling were highest (p<0.01) in those birds infected at an age of 12
      or 18 weeks. The serum protein and triiodothyronine (T3) levels did not differ
      significantly (p>0.05) between any of the groups. Thyroxine (T4) was
      significantly different between the groups infected at 6 and 18 weeks of age
      (p<0.05), and those at 6 and 24 weeks of age (p<0.01). The thyroid hormone levels
      correlated significantly with the FEC. Age does not seem to play a major role in
      resistance to A. galli infections in layers, whereas a bird's hormonal and immune
      status, related to laying activity, seems to have a significant negative impact
      on resistance.

PMID- 15725545
TI  - Participation of Rhipicephalus sanguineus (Acari: Ixodidae) in the epidemiology
      of canine visceral leishmaniasis.
AB  - The vectorial competence of the tick Rhipicephalus sanguineus is discussed in
      relation to the epidemiology of canine visceral leishmaniasis, taking into
      account its strict association with dogs and the low indices of natural infection
      presented by its known vector, the phlebotomine sand fly Lutzomyia longipalpis.
      In order to evaluate natural infection by Leishmania chagasi and the infectivity
      of these parasites in the tick, 39 specimens (6 females, 11 males and 22 nymphs)
      of R. sanguineus were removed from 21 dogs showing diverse symptoms of zoonotic
      visceral leishmaniasis (ZVL). Six ticks (15.4%) gave positive results for the
      genus Leishmania using the PCR technique. To determine the infectivity of the
      parasites, 36 hamsters were inoculated orally and peritoneally with macerates of
      ticks removed from nine dogs symptomatic for visceral leishmaniasis. After 6
      months the hamsters were sacrificed and necropsied. Serum was removed for IFAT,
      as well as spleen and liver fragments to make imprint smears and for PCR. Eight
      (88.9%) of these dogs presented ticks that were infective for 14 hamsters
      (41.2%), 12 (85.7%) of them infected peritoneally and two (14.3%) orally. PCR
      revealed 27 smears (40.9%) to be positive, 20 (62.5%) of them infected
      peritoneally and seven (20.6%) orally. IFAT showed 14 positive animals (41.2%).
      Based on these findings, we suggest that the vectorial capacity of R. sanguineus
      for L. chagasi should be evaluated further, opening new perspectives in the
      epidemiology of ZVL.

PMID- 15725546
TI  - Cattle grub infestation by Hypoderma sp. in Albania and risks for European
      countries.
AB  - In order to estimate the presence and the seroprevalence of hypodermosis in
      Albania, 625 head of cattle were bled during two sampling seasons (i.e. from
      February to March 2003 and from November to December 2003). The cattle came from
      three collection sites in Northern (site A), Central (site B) and Southern (site
      C) Albania. Milk samples were collected monthly from four animals from October
      2002 to May 2003 during the lactating period. The animals were also clinically
      examined for the presence of warbles by manual palpation from April to July 2003
      and 2004 and third instar larvae were collected and morphologically identified.
      Serum and milk samples were processed by ELISA. One hundred and thirty-three
      (38.6%) out of 344 and 116 (41.3%) out of 281 animals were found to be
      seropositive for Hypoderma during the first and the second sampling season. In
      particular, the animals from site C presented the highest percentage of
      seropositive results (i.e. 72.8% and 97.8% in the first and in second year,
      respectively) followed by the animals from sites A (i.e. 35.8% and 23.8% in the
      first and in second year, respectively) and B (i.e. 17.8% and 3.4% in the first
      and in second year, respectively). The kinetics of anti-Hypoderma antibodies in
      milk samples showed the highest antibody titres from October to February 2003.
      All the seropositive animals in both the sampling periods showed the presence of
      one or more warbles under the skin during April and May 2003 and 2004 and the
      third-stage larvae collected were morphologically identified as Hypoderma bovis.
      The results of this survey indicate that hypodermosis is widespread in Albania
      and that early prophylactic treatments must be carried out accordingly. The hope
      is not only to reduce the parasitic intensity with obvious benefits for livestock
      production, but also to avoid the risk of spreading this parasitic disease to
      neighboring countries.

PMID- 15725547
TI  - Antibodies to Neospora caninum in the blood of European bison (Bison bonasus
      bonasus L.) living in Poland.
AB  - The prevalence of antibodies to Neospora caninum was examined in European bison
      (Bison bonasus bonasus L.) living in free and fenced areas in Poland. Sera of 320
      European bison, different ages and sexes, from breeding areas in Poland were
      tested for N. caninum antibodies using ELISA test. Positive antibody responses
      were found in 23 bison (prevalence 7.3%). Additionally, all positive sera were
      tested by Western blot to verify the ELISA results. The Western blot results
      confirmed the presence of antibodies to Neospora tachyzoites antigens in all 23
      sera tested. The antibodies were detected against a wide range of NC-1 tachyzoite
      antigens. The antibody responses were directed against proteins at: 9.5, 17, 21,
      27, 31, 36.5, 38, 40, 43, 47, 48.5, 53.5 and 58 kDa. The most heavily stained
      bands had molecular weights of 9.5, 17, 27 and 58 kDa. The most important is that
      antibody to N. caninum was detected for the first time in sera from bison cow
      shot in 1988. It is the year of recognition of this protozoan parasite. Our
      results indicate strongly the presence of N. caninum in European bison in Poland
      and suggest that a sylvatic cycle of N. caninum can exist. However, further
      studies are needed to evaluate the existence of a sylvatic cycle of N. caninum.
      The study on the effect of the infection on the health status and conservation of
      European bison should be taken under consideration too.

PMID- 15725548
TI  - Pharmacokinetics of ivermectin in zebu Gobra (Bos indicus).
AB  - Plasma disposition kinetics of ivermectin was evaluated in a West African cattle
      breed. Five clinically healthy zebu Gobra cattle (Bos indicus) weighing 220-270
      kg were treated (0.2 mg kg-1) with a commercially available ivermectin
      formulation for cattle. Blood samples were collected by jugular puncture at
      different times between 0.5 h and 40 days post-treatment. After plasma extraction
      and derivatization, samples were analysed by HPLC with fluorescence detection.
      Ivermectin was detected in plasma between 30 min and 20 days post-treatment. The
      observed peak plasma concentration (Cmax) was 46.3+/-13.8 ng ml-1 and the time to
      reach Cmax (t(max)) was 0.9+/-0.2 day. The values for the absorption half-life
      (t1/2ab) and the elimination half-life (t1/2el) were 0.3+/-0.2 and 2.8+/-0.7
      days, respectively. The calculated area under the concentration-time curve (AUC)
      was 185.2+/-12.1 ng day ml-1 and the mean residence time (MRT) was 4.2+/-1.3
      days. The availability of ivermectin is low in zebu Gobra in comparison to other
      breeds cattle but equivalent to that reported in the yak and is likely to be due
      to physiological characteristics of this breed.

PMID- 15725549
TI  - Design and process aspects of laboratory scale SCF particle formation systems.
AB  - Consistent production of solid drug materials of desired particle and
      crystallographic morphologies under cGMP conditions is a frequent challenge to
      pharmaceutical researchers. Supercritical fluid (SCF) technology gained
      significant attention in pharmaceutical research by not only showing a promise in
      this regard but also accommodating the principles of green chemistry. Given that
      this technology attained commercialization in coffee decaffeination and in the
      extraction of hops and other essential oils, a majority of the off-the-shelf SCF
      instrumentation is designed for extraction purposes. Only a selective few vendors
      appear to be in the early stages of manufacturing equipment designed for particle
      formation. The scarcity of information on the design and process engineering of
      laboratory scale equipment is recognized as a significant shortcoming to the
      technological progress. The purpose of this article is therefore to provide the
      information and resources necessary for startup research involving particle
      formation using supercritical fluids. The various stages of particle formation by
      supercritical fluid processing can be broadly classified into delivery, reaction,
      pre-expansion, expansion and collection. The importance of each of these
      processes in tailoring the particle morphology is discussed in this article along
      with presenting various alternatives to perform these operations.

PMID- 15725550
TI  - Hydrodynamics-induced variability in the USP apparatus II dissolution test.
AB  - The USP tablet dissolution test is an analytical tool used for the verification
      of drug release processes and formulation selection within the pharmaceutical
      industry. Given the strong impact of this test, it is surprising that operating
      conditions and testing devices have been selected empirically. In fact, the flow
      phenomena in the USP test have received little attention in the past. An
      examination of the hydrodynamics in the USP apparatus II shows that the device is
      highly vulnerable to mixing problems that can affect testing performance and
      consistency. Experimental and computational techniques reveal that the flow field
      within the device is not uniform, and dissolution results can vary dramatically
      with the position of the tablet within the vessel. Specifically, computations
      predict sharp variations in the shear along the bottom of the vessel where the
      tablet is most likely to settle. Experiments in which the tablet location was
      carefully controlled reveal that the variation of shear within the testing device
      can affect the measured dissolution rate.

PMID- 15725551
TI  - Determination of the in vitro disintegration profile of rapidly disintegrating
      tablets and correlation with oral disintegration.
AB  - The assessment of the in vitro disintegration profile of rapidly disintegrating
      tablets (RDT) is very important in the evaluation and the development of new
      formulations of this type. So far neither the US Pharmacopoeia nor the European
      Pharmacopoeia has defined a specific disintegration test for RDT; currently, it
      is only possible to refer to the tests on dispersible or effervescent tablets for
      the evaluation of RDT's disintegration capacity. In the present study, we have
      evaluated the disintegration profile of RDT manufactured by main commercialised
      technologies, using the texture analyser (TA). In order to simulate as much as
      possible the oral disintegration of these dosage forms, a new operating structure
      was developed. This structure mimics the situation in the patient's mouth and
      provides a gradual elimination of the detached particles during the
      disintegration process. The obtained time-distance profiles or disintegration
      profiles enabled the calculation of certain quantitative values as the
      disintegration onset (t1) and the total disintegration time (t2). These values
      were used in the characterisation of the effect of test variables as the
      disintegration medium and temperature on the disintegration time of RDT.
      Moreover, the oral disintegration time of the same products was evaluated by 14
      healthy volunteers. Results obtained when artificial saliva at 37 degrees C was
      employed as disintegration medium were used to correlate the in vitro (t2) and
      oral disintegration times. Excellent correlation was found and in addition, we
      were able to achieve a qualitative measure of the mouthfeel by comparing the
      thickness of the tablets and the penetration distance obtained from the
      disintegration profile. This method also permitted the discrimination between
      different RDT, where differences in the disintegration mechanism were reflected
      on the disintegration profile achieved for each tablet.

PMID- 15725552
TI  - PLA-PEG particles as nasal protein carriers: the influence of the particle size.
AB  - Previous studies have shown that PLA-PEG nanoparticles (NP) are able to enhance
      the transport of the encapsulated model protein, tetanus toxoid (TT), across the
      rat nasal mucosa. The aim of this work was to study if the size of PLA-PEG
      particles affects the nasal transport of the encapsulated protein and, also, the
      potential contribution of blank nanoparticles to the transport of the free
      protein. To achieve this purpose, 125I-TT was encapsulated into PLA-PEG particles
      of different sizes (200 nm, 1.5, 5 and 10 microm) prepared by the water-in-oil-in
      water solvent evaporation technique. Firstly, in order to investigate the carrier
      role of the particles, two series of either conscious or anaesthetized rats were
      nasally treated with 125I-TT-loaded NP, free 125I-TT, and a physical mixture of
      blank NP and free 125I-TT. Secondly, the influence of the particle size on the
      nasal transport of TT encapsulated into PLA-PEG particles was evaluated in
      conscious rats. The amount of radioactivity recovered in the blood compartment,
      lymph nodes and other relevant tissues was monitored for up to 24h. Finally, the
      nasal bioavailability of 125I-TT-loaded PLA-PEG NP was calculated. The results
      indicated that the use of anaesthesia enhances the transport of 125I-TT and that
      the physical presence of PLA-PEG NP does not affect the transport of the toxoid.
      In contrast, when TT was encapsulated into the particles its transport across the
      nasal mucosa of conscious rats was significantly enhanced. Furthermore, the
      efficacy of this transport was related to the particle size, reaching the most
      important transport for the smallest particle size. The intensity of this
      transport was also illustrated by the high nasal bioavailability of TT
      encapsulated into nanoparticles (200 nm) (F = 70-80%). These results led us to
      conclude that PLA-PEG NP can be accepted as nasal protein carriers for nasal
      administration.

PMID- 15725553
TI  - Rheological characterization of Microcrystalline Cellulose/Sodiumcarboxymethyl
      cellulose hydrogels using a controlled stress rheometer: part I.
AB  - Rheological properties of two different commercial grades of Microcrystalline
      Cellulose/Sodiumcarboxymethyl Cellulose (MCC/NaCMC) hydrogels were investigated.
      A controlled stress rheometer fitted with parallel plate geometry was used.
      Application of the Cross Model relating the viscosity and shear rate data
      indicated the gels are extremely shear thinning. The two grades of Avicel (RC-591
      and CL-611) made of varying MCC and NaCMC concentrations, exhibited
      distinguishable changes in yield stress and shear thinning behavior attributable
      to the individual composition. The hydrogels reached structural equilibrium in 1
      week after manufacture. Lot to lot variability of Formula A hydrogels had minimal
      influence on the rheological properties of the resulting hydrogels. The yield
      stress and/or initial viscosity values observed were proportional to the
      concentration or phase volume of the MCC/NaCMC in water.

PMID- 15725554
TI  - Rheology of Microcrystalline Cellulose and Sodiumcarboxymethyl Cellulose
      hydrogels using a controlled stress rheometer: part II.
AB  - Rheological properties of two different commercial grades of Microcrystalline
      Cellulose/Sodiumcarboxymethyl Cellulose (MCC/NaCMC) hydrogels were investigated.
      Viscoelastic characterization of the hydrogels using a controlled stress
      rheometer revealed that structure formation in the gels could be detected at a
      concentration as low as 1.0% w/w MCC/NaCMC in purified water. The elastic modulus
      (G') and the linear viscoelastic region (LVR) increased with increase in hydrogel
      concentration. The frequency sweep study of the hydrogels exhibited a flat G',
      indicating a stable structure at 1.5% w/w and 2.0% w/w concentrations. The
      oscillation time sweep study indicated that the rate of structure build up was
      dependent on the concentration of hydrogel. Structure buildup at various
      temperatures indicated that structure formation was rapid at higher temperature
      (40 degrees C), and the gel point was reached fairly quickly. Phase volume of the
      hydrogel significantly influenced structural recovery at different temperatures.

PMID- 15725555
TI  - Analysis of macromolecular changes and drug release from hydrophilic matrix
      systems.
AB  - The influence of water-soluble and insoluble excipients on dynamics of hydration,
      front movement, erosion, and drug release from hydrophilic matrix tablets
      containing water-soluble drug was studied. Tablets were manufactured by direct
      compression, and their un-constrained swelling behavior and gel strength were
      assessed with a texture analyzer. Dissolution was performed using USP 26
      apparatus II modified by insertion of a mesh to prevent sticking of tablets to
      the bottom of the vessel and to allow free three-dimensional matrix swelling.
      Significant release differences between tablet batches were observed and this was
      consistent with changes in swelling rate, gel thickness, and swelling front
      movement within the tablets. Matrices containing approximately 30% drug load and
      water-soluble lactose, demonstrated more pronounced swelling front movement and
      hence drug release relative to the matrix tablets containing dicalcium phosphate
      dihydrate. The observed differences in release were verified by calculating the
      similarity and difference factors. The interdependence of front movement and mass
      erosion in relation to excipient types on progression of swelling front movement
      and alteration of water penetration, erosion, and drug release are explained. It
      is concluded that unlike in conventional dosage forms inclusion of excipients in
      hydrophilic controlled-release tablets containing water-soluble drugs should be
      carefully analyzed as their various physico-chemical properties may have
      significant implications on swelling dynamics, front movement, drug release
      kinetics, and consequently in vivo performance.

PMID- 15725556
TI  - Solubility of drugs in aqueous solutions. Part 5. Thermodynamic consistency test
      for the solubility data.
AB  - This paper is devoted to the verification of the quality of experimental data
      regarding the solubility of sparingly soluble solids, such as drugs,
      environmentally important substances, etc. in mixed solvents. A thermodynamic
      consistency test based on the Gibbs-Duhem equation for ternary mixtures is
      suggested. This test has the form of an equation, which connects the solubilities
      of the solid, and the activity coefficients of the constituents of the solute
      free mixed solvent in two mixed solvents of close compositions. The experimental
      data regarding the solubility of sparingly soluble substances can be verified
      with the suggested test if accurate data for the activity coefficients of the
      constituents of the solute-free mixed solvent are available. The test was applied
      to a number of systems representing the solubilities of sparingly soluble
      substances in mixed solvents. First, the test was scrutinized for four nonaqueous
      systems for which accurate solubility data were available. Second, the suggested
      test was applied to a number of systems representing experimental data regarding
      the solubility of sparingly soluble substances in aqueous mixed solvents.

PMID- 15725557
TI  - Dispersion of microemulsion drops in HEMA hydrogel: a potential ophthalmic drug
      delivery vehicle.
AB  - Approximately 90% of all ophthalmic drug formulations are now applied as eye
      drops. While eye-drops are convenient and well accepted by patients, about 95% of
      the drug contained in the drops is lost due to absorption through the conjunctiva
      or through the tear drainage. A major fraction of the drug eventually enters the
      blood stream and may cause side effects. The drug loss and the side effects can
      be minimized by using disposable soft contact lenses for ophthalmic drug
      delivery. The essential idea is to encapsulate the ophthalmic drug formulations
      in nanoparticles, and disperse these drug-laden particles in the lens material.
      Upon insertion into the eye, the lens will slowly release the drug into the pre
      lens (the film between the air and the lens) and the post-lens (the film between
      the cornea and the lens) tear films, and thus provide drug delivery for extended
      periods of time. This paper focuses on dispersing stabilized microemulsion drops
      in poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels. The results of this study
      show that the p-HEMA gels loaded with a microemulsion that is stabilized with a
      silica shell are transparent and that these gels release drugs for a period of
      over 8 days. Contact lenses made of microemulsion-laden gels are expected to
      deliver drugs at therapeutic levels for a few days. The delivery rates can be
      tailored by controlling the particle and the drug loading. It may be possible to
      use this system for both therapeutic drug delivery to eyes and the provision of
      lubricants to alleviate eye problems prevalent in extended lens wear.

PMID- 15725559
TI  - Stability assessment of pharmaceuticals by isothermal calorimetry: two component
      systems.
AB  - Isothermal calorimetry offers the potential to determine rapidly the stability of
      formulated pharmaceuticals because it is indifferent to physical form and
      sensitive enough to detect extremely small powers; ca. 50 nW at 25 degrees C.
      However, its use in this area is not widespread, principally because the power
      time data obtained often comprise contributions from more than one process and
      are thus difficult to analyse quantitatively. In this work, we demonstrate how
      power-time data recorded for systems in which two components are degrading in
      parallel (in this case, binary mixtures of selected parabens) can be analysed
      using a kinetic-based model; the methodology allows the determination of the
      first-order rate constant and reaction enthalpy for each process, so long as one
      rate constant is at least twice the magnitude of the other. It was found that the
      reactions did not need to run to completion in order for the analysis to be
      successful; a minimum of 15 min of data were required for samples with one
      degrading component and a minimum of 4 h of data were required for samples with
      two degrading components. It was observed that the rate constants for paraben
      degradation in binary systems were significantly lower than expected. This was
      ascribed to the fact that the parabens degrade to a common product and is an
      important factor that should be accounted for when the two or more parabens are
      formulated together.

PMID- 15725558
TI  - Effect of lactic acid and iontophoresis on drug permeation across rabbit ear
      skin.
AB  - The aim of this paper was to explore the efficacy of lactic acid as permeation
      enhancer for drug molecules across the skin. Three model permeants were chosen:
      acetaminophen (non-ionized), buspirone hydrochloride (cationic drug) and
      ibuprofen lysine (anionic drug). We also explored the association of lactic acid
      and iontophoresis as a means of enhancing drug delivery. Permeation experiments
      were performed in vitro, using rabbit ear skin as barrier. The results obtained
      indicate that lactic acid has some effects on model drug permeation across the
      skin. The effect was more evident with the anionic drug ibuprofen. Cathodal
      intophoresis increased ibuprofen transport, but when lactic acid was associated
      with cathodal iontophoresis, a concentration-dependent reduction of ibuprofen
      iontophoretic flux was observed, probably for the competition by the co-ion. The
      application of electric current (anodal iontophoresis) to a solution of
      acetaminophen produced an increase in its transport, due to the presence of an
      electroosmotic contribution; however, the effect of the association of anodal
      iontophoresis and lactic acid produced no further enhancement.

PMID- 15725560
TI  - The use of colloidal microgels as a (trans)dermal drug delivery system.
AB  - A co-polymer of poly(N-isopropylacrylamide) (85%) co-butyl acrylate (10%) co
      methacrylic acid (5%) (NIPAM/BA/MAA) (85/10/5) microgel was synthesised and
      investigated as a potential pH and temperature sensitive transdermal delivery
      device. Three compounds having different octanol/water partition coefficients and
      solubilities were incorporated into the microgel, namely: salicylamide (SA),
      methyl paraben (MP) and propyl paraben (PP). Physico-chemical characterisation of
      these microgel-drug complexes showed that microgels incorporating MP and SA have
      smaller volumes after changing environmental pH or temperature when compared with
      the co-polymer NIPAM/BA/MAA (85/10/5) alone. This reduction in volume could be
      attributed to the incorporation of the compounds into the microgel particles,
      having a shielding effect on the charged groups present within the network.
      Diffusion studies, across human skin, were performed at 305K in the range of pH 3
      7 for saturated solutions of SA, MP and PP, and for microgel particles
      incorporating the three compounds. The transport rate for these microgels
      incorporating MP was reduced by 2/3-fold compared to the saturated solution, by
      one order of magnitude for PP, meanwhile the transport rate for these microgels
      incorporating SA is the same order of magnitude as that for the corresponding
      saturated solutions. Transdermal release studies of the saturated colloidal
      dispersions indicated that pH control of the drug release was marginal. The
      incorporation of compounds into the pH/temperature sensitive co-polymer
      NIPAM/BA/MAA (85/10/5) and the subsequent release depends on the octanol/water
      partition coefficient and solubility of the respective compound.

PMID- 15725561
TI  - Enhanced paclitaxel bioavailability after oral coadministration of paclitaxel
      prodrug with naringin to rats.
AB  - The aim of this study was to investigate the effect of naringin on the
      bioavailability and pharmacokinetics of paclitaxel after oral administration of
      paclitaxel or its prodrug coadministered with naringin to rats. Paclitaxel (40
      mg/kg) and prodrug (280, 40 mg/kg paclitaxel equivalent) were coadministered
      orally to rats with naringin (1, 3, 10 and 20 mg/kg). The plasma concentrations
      of paclitaxel coadministered with naringin increased significantly (p<0.01 at
      paclitaxel, p<0.05 at prodrug) compared to the control. The areas under the
      plasma concentration-time curve (AUC) and the peak concentrations (C(max)) of
      paclitaxel with naringin significantly higher (p<0.01) than the control. The half
      life (t(1/2)) was significantly (p<0.05) longer than the control. The absolute
      bioavailability (AB, %) of paclitaxel with naringin was significantly higher (3.5
      6.8%, p<0.01) than the control (2.2%). Absorption rate constant (K(a)) of
      paclitaxel with naringin increased, but not significantly. The AUC of paclitaxel
      after coadministration of prodrug with naringin to rats was significantly
      (p<0.05) higher than the prodrug control. The relative bioavailability (RB, %) of
      paclitaxel after coadministration of prodrug with naringin was 1.35-1.69-fold
      higher than prodrug control. The absolute bioavailability (AB, %) of paclitaxel
      after coadministration of prodrug with naringin increased significantly (p<0.05)
      from 6.6 to 9.0% and 11.2%. The bioavailability of paclitaxel coadministered as a
      prodrug with or without naringin was remarkably higher than the control.
      Paclitaxel prodrug, a water-soluble compound concerning with its physicochemical
      properties, passes through the gastrointestinal mucosa more easily than
      paclitaxel without obstruction of P-gp and cytochrome P-450 in the
      gastrointestinal mucosa. Oral paclitaxel preparations which is more convenient
      than the IV dosage forms could be developed with a prodrug form with naringin.

PMID- 15725562
TI  - Stable ciliary activity in human nasal epithelial cells grown in a perfusion
      system.
AB  - PURPOSE: Explore the usefulness of a perfusion system in order to establish human
      nasal epithelial cell cultures suitable for long-term in vitro ciliary beat
      frequency (CBF) and cilio-toxicity studies. METHODS: The cells were obtained by
      protease digestion of nasal biopsy material. The cells were plated at a density
      of 0.8-1 x 10(6)/cm2 on Vitrogen-coated polyethylene terephthalate membranes, and
      cultured under submerged conditions in a CO2 incubator or in a perfusion system
      (initiated on days 8-9 after plating). The CBF was determined at 24.1 +/- 0.8
      degrees C by a computerized microscope photometry system. The morphology of the
      cultured cells was characterized by transmission electron microscopy (TEM).
      RESULTS: Under CO2 incubator culture conditions, stable ciliary activity was
      expressed and maintained from day 2 to day 24. Under perfusion system culture
      conditions, the CBF (mean+/-S.D., n = 4) amounted to 8.4 +/- 0.9 and 8.8 +/- 0.4
      Hz on days 7 and 14, respectively. These values were lower as compared to the
      corresponding CBF obtained in the CO2 incubator cultures (9.5 +/- 0.6 and 9.9 +/-
      1.0 Hz, respectively). Reference cilio-stimulatory (glycocholate) and cilio
      inhibitory (chlorocresol) compounds were used to assess CBF reactivity. In the
      CO2 incubator and 7- and 14-days perfusion system cultures, glycocholate (0.5%)
      showed a reversible cilio-stimulatory effect of 23, 26 and 21%, respectively,
      while chlorocresol (0.005%) exerted a reversible cilio-inhibitory effect of 36,
      40 and 36%, respectively. TEM revealed polarized cuboidal to columnar epithelial
      morphology, with well-differentiated ciliated cells under CO2 and perfusion
      system conditions (up to day 23). CONCLUSION: Culturing human nasal epithelial
      cells on Vitrogen-coated polyethylene terephthalate membranes in submerged
      conditions in a CO2 incubator and in a perfusion system offers the possibility
      for long-term preservation (up to 22-24 days) of stable and reactive CBF in
      vitro.

PMID- 15725563
TI  - Bioadhesive oesophageal bandages: protection against acid and pepsin injury.
AB  - The rate of acid and pepsin diffusion through solutions of sodium alginate was
      measured using in vitro techniques. Previous work has demonstrated that solutions
      of alginate may adhere to the oesophagus for up to 60 min; this work measured
      their ability to protect the oesophageal epithelial surface from damage caused by
      refluxed acid and pepsin. Franz diffusion cells were used to measure the rate of
      acid and pepsin diffusion through an alginate layer. The effect of the type of
      alginate, alginate concentration and depth of alginate applied were investigated.
      The rate of both acid and pepsin diffusion was significantly reduced (ANOVA
      analysis; P<0.05) in the presence of an alginate solution compared to the
      control. A 2% (w/v) alginate solution with a high guluronic acid component, in a
      layer of 0.44 mm depth, demonstrated the greatest reduction in acid diffusion
      with a permeation coefficient 14% than that of a control value. All three
      alginates demonstrated significant reductions in acid diffusion with both
      increasing depth and increasing concentration, as expected. Pepsin diffusion was
      also significantly reduced as the depth and concentration of applied alginate
      increased. This study demonstrates that an adhesive layer of alginate present
      within the oesophagus will limit the contact of refluxed acid and pepsin with the
      epithelial surface.

PMID- 15725564
TI  - Drug interaction and location in liposomes: correlation with polar surface areas.
AB  - An important step in liposome characterization is to determine the location of a
      drug within the liposome. This work thus investigated the interaction of
      dipalmitoylphosphatidylcholine liposomes with drugs of varied water solubility,
      polar surface area (PSA) and partition coefficient using high sensitivity
      differential scanning calorimetry. Lipophilic estradiol (ES) interacted strongest
      with the acyl chains of the lipid membrane, followed by the somewhat polar 5
      fluorouracil (5-FU). Strongly hydrophilic mannitol (MAN) showed no evidence of
      interaction but water soluble polymers inulin (IN) and an antisense
      oligonucleotide (OLG), which have very high PSAs, interacted with the lipid head
      groups. Accordingly, the drugs could be classified as: hydrophilic ones situated
      in the aqueous core and which may interact with the head groups; those located at
      the water-bilayer interface with some degree of penetration into the lipid
      bilayer; those lipophilic drugs constrained within the bilayer.

PMID- 15725565
TI  - Cutaneous bioassay of salicylic acid as a keratolytic.
AB  - Keratolytic efficacy of topical preparations containing salicylic acid was
      studied in humans utilizing adhesive tape stripping and quantifying SC removal by
      protein analysis. In combination with tape stripping, squamometry was used to
      evaluate the influence of salicylic acid on skin surface scaliness and
      desquamation. Furthermore, skin barrier perturbation and skin irritancy was
      recorded and related to the dermatopharmacological effect of the preparations. In
      contrast to squamometry, tape stripping combined with protein analysis was
      sensitive in detecting keratolytic effect of salicylic acid within hours of
      application. Importantly, whereas the pH of the preparations only minimally
      influenced efficacy, local dermatotoxicity was significantly increased at acidic
      pH. This indicates that the quest to increase the amount of free, non-dissociated
      SA is, in fact, counterproductive as the more acidic preparations resulted in
      skin irritation and barrier disruption.

PMID- 15725566
TI  - Microbiological assay of ketoconazole in shampoo.
AB  - Ketoconazole, an anti-fungal agent, is often incorporated in several
      pharmaceutical forms and in shampoo formulation it is known to be effective
      against fungal infection on the scalp. This paper describes a method to quantify
      ketoconazole in shampoo by comparing the cylinder plate assay and the HPLC
      method. The test organism used for the agar diffusion assay was Candida albicans
      ATCC 10231. Three different concentrations of ketoconazole were used for the
      diffusion assay. A mean zone diameter was obtained for each concentration. A
      standard curve was obtained by plotting the three values derived from the zone
      diameters. A prospective validation of the method showed that the method was
      linear (r = 0.9982), precise (R.S.D. = 2.57%) and accurate. The results obtained
      by the two methods were statistically evaluated by analysis of variance (ANOVA)
      and the results obtained indicate that there is no significant difference between
      these two methods.

PMID- 15725567
TI  - A comparison of two methods to determine the solubility of compounds in aerosol
      propellants.
AB  - A new on-line reverse phase HPLC method for determining the solubility of
      compounds in propellant based metered dose inhaler (MDI) formulations was
      compared with a conventional method. The new method employs a direct injection
      from a MDI vial into the needle injector port of a manual injector. To evaluate
      the two methods, beclomethasone dipropionate (BDP), 5,5-diphenyl hydantoin and
      3,3'-diindolylmethane, were used as model compounds in propellant HFA-134a.
      Comparison was performed by analyzing known and unknown concentrations of BDP in
      various combinations of HFA-134a and ethanol. In addition, the solubility of 5,5
      diphenyl hydantoin and 3,3'-diindolylmethane were determined in HFA-134a using
      both the new and the conventional methods. The two methods were found to be in
      good agreement with each other, with the new direct injection technique offering
      enhanced precision and accuracy along with considerable reduction in analysis
      time.

PMID- 15725568
TI  - Particle size distribution and evolution in tablet structure during and after
      compaction.
AB  - The objective of this study was to investigate the effect of the distribution in
      size of free-flowing particles for the evolution in tablet structure and tablet
      strength. For sucrose and sodium chloride, three powders of different size
      distributions were prepared by mixing predetermined quantities of particle size
      fractions. For paracetamol, three batches with varying particle size
      distributions were prepared by crystallisation. The powders were formed into
      tablets. Tablet porosity and tensile strength were determined directly after
      compaction and after short-term storage at two different relative humidities.
      Tablets were also formed after admixture of a lubricant (magnesium stearate) and
      the tablet tensile strength was determined. For the test materials used in this
      study, the spread in particle size had no influence on the evolution in tablet
      porosity and tensile strength during compression. However, the spread in particle
      size had a significant and complex influence on the short-term post-compaction
      increase in tablet tensile strength. The effect of the spread was related to the
      instability mechanism and the presence of lubricant. It is concluded that the
      distribution in size of free-flowing particles is not critical for the tablet
      porosity but may give significant effects on tablet tensile strength due to a
      post-compaction reaction.

PMID- 15725570
TI  - Induction of apoptosis of human lung carcinoma cells by hybrid liposomes
      containing polyoxyethylenedodecyl ether.
AB  - Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular
      and micellar molecules in aqueous solution. A clear solution of hybrid liposomes
      composed of 90 mol% dimyristoylphosphatidylcholine (DMPC) and 10 mol%
      polyoxyethylene(23)dodecyl ether (C12(EO)23) having a hydrodynamic diameter of
      100-120 nm was obtained. Highly inhibitory effects of hybrid liposomes of 90 mol%
      DMPC/10 mol% C12(EO)23 on the growth of human lung carcinoma (RERF-LC-OK and
      A549) cells without any drugs were obtained. Induction of apoptosis by hybrid
      liposomes in RERF-LC-OK and A549 cells was verified on the basis of fluorescence
      microscopy, agarose gel electrophoresis of DNA and flow cytometry. We elucidated
      the pathway of apoptosis induced by hybrid liposomes as follows: (a) accumulation
      of hybrid liposomes in tumor cell membrane was revealed using microphysiometer.
      (b) Reduction of mitochodrial membrane potential and activation of caspase-9, -3
      and -8 were obtained, indicating that apoptotic signal by hybrid liposomes should
      pass through mitochondria and these caspases. It is worthy to note that such a
      novel mechanism of apoptosis induced by hybrid liposomes without any drugs was
      performed for the first time in human lung carcinoma cells.

PMID- 15725569
TI  - The use of microviscometry to study polymer dissolution from solid dispersion
      drug delivery systems.
AB  - Solid dispersions can be used to improve dissolution of poorly soluble drugs and
      PVP is a common polymeric carrier in such systems. The mechanisms controlling
      release of drug from solid dispersions are not fully understood and proposed
      theories are dependent on an understanding of the dissolution behaviour of both
      components of the dispersion. This study uses microviscometry to measure small
      changes in the viscosity of the dissolution medium as the polymer dissolves from
      ibuprofen-PVP solid dispersions. The microviscometer determines the dynamic and
      kinematic viscosity of liquids based on the rolling/falling ball principle. Using
      a standard USP dissolution apparatus, the dissolution of the polymer from the
      solid dispersion was easily measured alongside drug release. Drug release was
      found to closely follow polymer dissolution at the molecular weights and ratios
      used. The combination of sensitivity and ease of use make microviscometry a
      valuable technique for the elucidation of mechanisms governing drug release from
      polymeric delivery systems.

PMID- 15725571
TI  - Experimental bullous pemphigoid generated in mice with an antigenic epitope of
      the human hemidesmosomal protein BP230.
AB  - Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease that
      targets the hemidesmosomal proteins BP230 and BP180. To investigate the
      pathogenic role of anti-BP230 antibodies, rabbit polyclonal antibodies were
      generated against an antigenic sequence of the human BP230 antigen (BPAG 1, 2479
      2499), which shows 67% homology in the human and the mouse BP230. Purified IgG
      from the rabbit anti-serum was transferred subcutaneously into the dorsal skin of
      neonatal isogeneic CBA/Ca (CBA) mice in a dose of 5 mg (n=7) or 1.2 mg IgG/50
      microl (n=16). After 24 h, 1 of the mice injected with 5 mg IgG exhibited
      blisters, but the dorsal skin of all 7 of them was erythematous, and gentle
      friction produced a fine persistent wrinkling of the epidermis in 4 mice. The
      mice injected with 1.2 mg IgG developed less severe symptoms. Immunohistological
      examinations revealed linear rabbit IgG and mouse C3 depositions along the
      basement membrane of the perilesional skin and subepidermal blister formation. An
      intradermal inflammatory reaction (granulocyte infiltration) was also detected.
      None of these symptoms was seen in mice injected with IgG from a control rabbit
      anti-serum. These findings demonstrate that antibodies against BP230 can elicit
      the clinical and immunopathological features of BP in neonatal mice, suggesting
      that anti-BP230 antibodies may possibly play a pathogenic role in this disease.

PMID- 15725572
TI  - Development of autoreactive diabetogenic T cells in the thymus of NOD mice.
AB  - Type 1 diabetes results from destruction of pancreatic beta cells by beta cell
      specific autoreactive T cells in the nonobese diabetic (NOD) mouse. Defects in
      thymic negative selection are thought to result in failure to delete potential
      beta cell-reactive T cells, contributing to the development of autoimmune
      diabetes. We investigated this possibility by comparing the deletion profile of
      double-positive (DP) thymocytes in NOD mice with diabetes-resistant strains of
      mice after anti-CD3 Ab treatment to trigger the TCR-mediated signaling pathway.
      We found that immature NOD CD4+CD8+ DP thymocytes have a lower activation
      threshold than C57BL/6 and Balb/c thymocytes. This was confirmed by showing that
      NOD DP thymocytes have a higher level of ERK and JNK phosphorylation. The low
      activation threshold of immature thymocytes resulted in rapid deletion of
      strongly activated immature DP thymocytes by negative selection, whereas weakly
      activated immature thymocytes differentiated more efficiently into CD69+CD3high
      DP thymocytes by positive selection. SP thymocytes, particularly CD4-CD8+ T cells
      that were efficiently generated from activated DP thymocytes, could induce severe
      insulitis and diabetes in NOD.scid mice. We conclude that the development of
      autoreactive diabetogenic T cells results from inordinate positive selection due
      to the low activation threshold of DP thymocytes in NOD mice.

PMID- 15725573
TI  - The involvement of autoimmunity against retinal antigens in determining disease
      severity in toxoplasmosis.
AB  - PURPOSE: Ocular lesions are frequent in various individuals infected with
      Toxoplasma gondii. Disease intensity in ocular toxoplasmosis varies greatly
      between patients. Autoimmunity has been suggested as a possible component to
      retinal destruction. METHODS: Immunologic parameters in the response to retina
      antigens were evaluated in infected persons with and without ocular lesions and
      in non-infected controls. Subjects were divided into groups on the basis of
      titers of serum antibodies to T. gondii, presence and severity of ocular lesions,
      and clinical history. RESULTS: Peripheral blood mononuclear cells from patients
      with mild disease responded to one or more retinal antigens with a significantly
      higher frequency than patients without disease or with severe disease.
      Interestingly, the cytokines produced by the proliferating mononuclear cells did
      not follow any specific patterns, except for the fact that IL-4 and IL-5 were
      seldom detected. CONCLUSIONS: Our results suggest that although the presence of
      an immune response towards autoantigens is not protective against the development
      of ocular lesions by the T. gondii, it may protect against the development of
      severe disease.

PMID- 15725574
TI  - Hepatitis B vaccination and central nervous system demyelination: an
      immunological approach.
AB  - Demyelination events or multiple sclerosis following hepatitis B virus (HBV)
      vaccination have been reported. We therefore compared the T-cell response to
      HBsAg in patients with CNS demyelination following HBV vaccination and in HBV
      vaccinated healthy individuals. Our data showed no differences in terms of T-cell
      proliferation or cytokine production between these groups and may help to allay
      concerns that HBV vaccination might trigger a deleterious immune response.

PMID- 15725575
TI  - SOCS5 mRNA levels in peripheral blood mononuclear cells (PBMC): a potential bio
      marker for monitoring response of uveitis patients to Daclizumab therapy.
AB  - Uveitis is an intraocular inflammatory disease mediated by Th1 lymphocytes.
      Therapy for severe uveitis is frequently long-term immunosuppression using
      systemic corticosteroids and cytotoxic agents, but side effects make long-term
      therapy difficult. Long-term humanized anti-interleukin-2 (IL-2) receptor alpha
      (Daclizumab) therapy has few side effects and is as effective as standard
      immunosuppression for treating severe uveitis. However, it is necessary to
      carefully monitor levels of activated T cells in the eye to allow prompt re
      institution of standard immunosuppressive therapy to non-responders to Daclizumab
      therapy. Suppressors of cytokine signaling (SOCS) are feedback regulators of
      Th1/Th2 cytokines. SOCS5 and SOCS3 are preferentially expressed in Th1 and Th2
      cells, respectively, and are thought to be lineage markers for T-helper cells. In
      this study, we have investigated whether SOCS3 or SOCS5 expression can serve as
      surrogate markers of T-cell levels in the eye. Compared to healthy volunteers,
      SOCS5 mRNA is significantly elevated in PBMC of uveitis patients while SOCS3 is
      decreased. However, after Daclizumab therapy SOCS5 mRNA level is significantly
      decreased, suggesting that SOCS5 mRNA can be used as diagnostic tool to monitor
      therapeutic response of uveitis patients. Our data also suggest that SOCS5 may
      serve as a new therapeutic target for uveitis and other autoimmune diseases.

PMID- 15725576
TI  - A peptide of human muscarinic acetylcholine receptor 3 is antigenic in primary
      Sjogren's syndrome.
AB  - To evaluate the antigenicity of a peptide representing a part of the second
      extracellular loop of the human muscarinic acetylcholine receptor 3 (m3AChR) with
      autoimmune sera from primary Sjogren's syndrome (pSS), enzyme-linked
      immunosorbent assays (ELISAs) were developed. On the basis of the computer
      predicted data, a 16-mer synthetic peptide KRTVPPGECFIQFLSE (KRSE213-228) was
      produced by solid-phase peptide synthesis. cDNA coding for the KRSE peptide was
      chemically synthetized and utilized to express the recombinant glutathione S
      transferase (GST)-KRSE fusion protein. The immunoreactivities of the two antigens
      were tested in ELISAs with the sera of 40 pSS patients and 40 healthy controls.
      The specificity of the reaction was confirmed by inhibition assays and
      immunoblottings. The pSS sera resulted in significantly higher mean optical
      densities than those of the healthy controls (KRSE: 0.4149 vs 0.1494, p<0.0001;
      GST-KRSE 0.4765 vs 0.1764, p<0.0001). The immunological recognition with the
      recombinant fusion antigen was significantly better than that for the free
      peptide (p=0.0068). The sensitivities of the assays were 77.5% (KRSE) and 97%
      (GST-KRSE). The results of the concentration-dependent inhibition assays by the
      two systems of peptide presentation indicated that the KRSE sequence is specific
      for pSS sera. This is the first demonstration of the antigenicity of a novel
      peptide fragment of the human m3AChR in pSS. The analysed peptide could be of
      diagnostic relevance.

PMID- 15725577
TI  - CD4+CD25high regulatory T cells in human autoimmune diabetes.
AB  - In mouse models, CD4+CD25+ T cells are involved in maintenance of peripheral
      tolerance. In humans, a subset of CD4+CD25+ T cells expressing high levels of
      CD25 (CD4+CD25high) with characteristics identical to murine CD4+CD25+ was
      recently described. We evaluated the characteristics of CD4+CD25high T cells in
      peripheral blood of type 1 diabetic subjects (T1D) and normal controls (NC). In
      contrast to a previous report, we found no difference in the number of
      CD4+CD25high and CD4+CD25+ T cells between T1D and NC. We confirmed previous
      studies that demonstrated that human CD4+CD25high cells can suppress the
      proliferation of co-cultured CD4+CD25- cells stimulated in conditions of sub
      maximal cross-linking by anti-CD3 either with or without anti-CD28. However, we
      did not observe statistical differences between the normal controls and the
      chronic diabetic subjects we tested. Culturing of these cell populations did not
      appear to affect their ability to suppress proliferation in both groups. In
      conclusion, we found no significant differences in number or in vitro regulatory
      function of CD4+CD25high in chronic human T1D subjects.

PMID- 15725579
TI  - Differential regulation of Cu, Zn- and Mn-superoxide dismutases by retinoic acid
      in normal and psoriatic human fibroblasts.
AB  - Superoxide dismutases' (SODs) expression is altered in several diseases including
      Alzheimer, atherosclerosis, cancer and psoriasis. Previously, we reported a
      marked increase in Mn-SOD and Cu,Zn-SOD functional activity in human dermal
      psoriatic fibroblasts. As retinoic acid (RA) has been used in the treatment of
      psoriasis and a mechanism for its beneficial effects is not understood, we
      investigated the effects of RA on SOD mRNA and protein expression levels in human
      normal and psoriatic fibroblasts. Prior to RA exposure, Cu,Zn-SOD protein and
      mRNA levels were similar in normal compared to psoriatic fibroblasts while Mn-SOD
      protein and mRNA levels were increased in psoriatic cells. However, in contrast
      to normal fibroblasts, exposure of psoriatic fibroblasts to 1 microM RA down
      regulated Mn-SOD mRNA, and also decreased Mn-SOD activity by approximately 80%
      with no change in Mn-SOD protein levels. In contrast, Cu,Zn-SOD protein and
      enzymatic activity were modestly reduced by RA treatment in both normal and
      psoriatic fibroblasts. Furthermore, RA treatment of psoriatic fibroblasts also
      caused a decrease in Cu,Zn-SOD steady-state mRNA levels. These results indicate
      that RA can serve as a regulatory agent to down-regulate the steady-state levels
      of both Mn-SOD and Cu,Zn-SOD in psoriatic cells. These findings offer a new model
      for the antiinflammatory activity of RA when used in the treatment of psoriasis.

PMID- 15725578
TI  - Tumor necrosis factor-alpha -308 promoter polymorphism contributes independently
      to HLA alleles in the severity of rheumatoid arthritis in Mexicans.
AB  - The aim of this study was to determine the frequency and potential relevance of
      the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha) in the
      severity of rheumatoid arthritis (RA) in Mexicans. HLA-DR and polymorphisms at
      positions -238 and -308 of TNF-alpha gene were determined in 137 Mexican RA
      patients (44 with severe and 93 with non-severe RA) as well as in 169 healthy
      controls (99 were typed for HLA-DR). We observed an increased frequency of HLA
      DR4 in severe RA compared to healthy controls (pC=0.02, OR=2.33). TNF
      polymorphism analysis showed a significant increased frequency of TNF -238 GG
      genotype in the whole group of RA patients when compared to healthy controls
      (pC=0.007, OR=4.71). When the analyses were carried out separately in severe and
      non-severe RA patients, the increased frequency of -238 GG genotype only was
      observed in patients with non-severe forms of the disease. Analysis of -308
      polymorphism showed increased frequency of -308 T2 (A) allele in severe RA when
      compared to non-severe disease (pC=0.011, OR=3.29) and to healthy controls
      (pC=0.002, OR=3.97). The data demonstrate that -308 T2 (A) allele is associated
      with susceptibility to develop severe RA in Mexicans. This association could be
      independent from HLA-DR alleles and might be used as a prognostic marker for
      severe RA.

PMID- 15725580
TI  - Clinical features and biochemical data of Caucasian children at diagnosis of
      autoimmune hepatitis.
AB  - OBJECTIVE: Evaluation of systematic epidemiological data regarding clinical
      characteristics, sex distribution and autoantibody pattern in Caucasian children
      with autoimmune hepatitis (AIH). STUDY DESIGN: Data of 142 children presenting
      with AIH (97 girls and 45 boys) have been analysed for their clinical,
      serological, and histological profile. RESULTS: Clinical findings were jaundice
      (58%), unspecific weakness (57%), anorexia (47%), abdominal pain (38%) and
      paleness (26%). One hundred and three children (73%) (68 girls, 35 boys, 1.9:1)
      had AIH type 1 and 35 patients (25%) (27 girls, 8 boys, 3.4:1) type 2 due to
      specific autoantibodies. Four children could not be classified. Histology of 122
      children revealed active hepatitis in 64 (52%), cirrhosis in 46 (38%), and mild
      inflammatory activity in 12 individuals (10%). The most prevalent HLA type was
      B8. CONCLUSION: In our cohort the prevalence of AIH was half as frequent in boys
      as in girls. Type 1 was the most frequent diagnosis (73%) and was more prevalent
      in older children. Type 2 was equally age distributed. The clinical presentation
      of AIH in children was unspecific and type I and type II could only be
      differentiated by the determination of the specific autoantibodies. Ninety
      percent of patients presented with high inflammatory activity or liver cirrhosis.

PMID- 15725581
TI  - Complications of anaesthesia in neuromuscular disorders.
AB  - The purpose of this review is to alert non-anaesthesiologists to the various
      complications from which patients with neuromuscular disorders and those
      susceptible to malignant hyperthermia can suffer during anaesthesia. The
      patient's outcome correlates with the quality of consultation between
      anaesthesiologists, surgeons, neurologists and cardiologists. Special precautions
      must be taken, since many anaesthetics and muscle relaxants can aggravate the
      clinical features or trigger life-threatening reactions. Complications frequently
      occur in these patients, although anaesthetic procedures have become safer by the
      reduced administration of suxamethonium and the use of total intravenous
      anaesthesia, new volatile anaesthetics and non-depolarising relaxants. This
      review provides a synopsis of pre-operative anaesthetic considerations and
      adverse drug effects on skeletal, cardiac and smooth muscle tissue. It describes
      the pathogenetic aspects of typical complications and introduces anaesthetic
      procedures for the various neuromuscular disorders, including regional
      anaesthesia for patients in whom a restriction of respiratory and/or cardiac
      function is predicted.

PMID- 15725582
TI  - Dystroglycan: important player in skeletal muscle and beyond.
AB  - Dystroglycan is a transmembrane protein that connects the extracellular matrix to
      the cytoskeleton. Given the ubiquitous tissue expression of dystroglycan,
      different functional roles in various organ systems have been characterized
      during the past decade. More recently, aberrant glycosylation of dystroglycan has
      been identified as a novel pathogenetic mechanism in several forms of congenital
      and late onset muscular dystrophy syndromes. The current review summarizes the
      recent scientific achievements as they relate to the function of dystroglycan
      under normal and pathophysiological conditions.

PMID- 15725583
TI  - The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.
AB  - Limb-girdle muscular dystrophy 2A (LGMD2A) is considered to be the most frequent
      LGMD. Our study surveyed an area in northeastern Italy where an almost complete
      ascertainment was possible. To identify LGMD2A patients we used a new diagnostic
      approach, including several molecular and biochemical methods. In 84 screened
      patients from northeastern Italy, we identified 39 LGMD2A patients, the
      prevalence of LGMD2A being 9.47 per million. In the Venezia district it appears
      higher than in other districts of the Veneto region, and in the Friuli region it
      is three times higher than in Veneto, due to the recurrence of single mutation.
      Haplotype analysis suggested a founder effect. The population from Venezia and
      Friuli has a higher risk of being heterozygote for these two mutant alleles than
      people from the rest of northeastern Italy. Our results indicate that LGMD2A is
      one of the most frequent autosomal recessive disorders, thus finding its
      molecular characterization becoming increasingly important.

PMID- 15725584
TI  - Localized expression of specific P2X receptors in dystrophin-deficient DMD and
      mdx muscle.
AB  - Using a combination of molecular and immunohistochemical methods, we have
      obtained evidence for a distinctive change in the expression patterns of ATP
      gated (P2X) receptor subunits in dystrophic muscle from both Duchenne muscular
      dystrophy (DMD) patients and the mdx mouse model. In control myofibres there was
      no staining for any P2X subtype studied here, although P2X1 stained the smooth
      muscle of the blood vessels and P2X6 nerves and the tunica intima in small
      arteries. In contrast, P2X1 and P2X6 were co-expressed strongly in small
      regenerating muscle fibres in the dystrophic muscles, whereas this expression
      decreased in fully regenerated fibres. Moreover, immunoreactivity for the P2X2
      receptor re-appeared in dystrophic muscle, where it co-localised with the Type 1
      fibres. There is, thus, a burst of production of several P2X receptor subtypes in
      regenerating dystrophic muscle, which may have implications for drug targets for
      this muscle pathology.

PMID- 15725585
TI  - Autologous transplantation of porcine myogenic precursor cells in skeletal
      muscle.
AB  - Myoblast transplantation is a potential therapy for severe muscle trauma,
      myopathies and heart infarct. Success with this therapy relies on the ability to
      obtain cell preparations enriched in myogenic precursor cells and on their
      survival after transplantation. To define myoblast transplantation strategies
      applicable to patients, we used a large animal model, the pig. Muscle
      dissociation procedures adapted to porcine tissue gave high yields of cells
      containing at least 80% myogenic precursor cells. Autologous transplantation of
      3[H]-thymidine labeled porcine myogenic precursor cells indicated 60% survival at
      day 1 followed by a decay to 10% at day 5 post-injection. Nuclei of myogenic
      precursor cells transduced with a lentivirus encoding the nls-lacZ reporter gene
      were present in host myotubes 8 days post-transplantation, indicating that
      injected myogenic precursor cells contribute to muscle regeneration. This work
      suggests that pig is an adequate large animal model for exploring myogenic
      precursor cells transplantation strategies applicable in patients.

PMID- 15725586
TI  - Characterization of MTM1 mutations in 31 Japanese families with myotubular
      myopathy, including a patient carrying 240 kb deletion in Xq28 without male
      hypogenitalism.
AB  - X-linked myotubular myopathy is a congenital muscle disorder due to MTM1
      mutation, and is characterized clinically by generalized muscle weakness and
      hypotonia at birth usually resulting in early death. We newly identified 26
      unrelated Japanese patients with MTM1 mutations by genomic DNA and transcript
      analysis, including 12 novel mutations. Among 31 patients, including our
      previously reported five patients, the c.1261-10A>G splice site mutation was the
      most frequent mutation. Three mutations, one missense and two splice site, were
      associated with milder phenotype. Of particular interest, one boy had a 240 kb
      deletion in Xq28 encompassing CXorf6 (formerly F18), MTM1 and MTMR1 but was not
      accompanied by hypogenitalism. CXorf6, which have been implicated in male sexual
      development, was not entirely deleted in this boy, resulting in the fusion with
      the MTMR1 gene. A chimeric fusion transcript was detected in patient's muscle by
      RT-PCR, suggesting this fusion gene product avoids the phenotype. This deletion
      led us to refine the critical region of CXorf6 for the development of male
      genitalia.

PMID- 15725587
TI  - Choline acetyltransferase expression does not identify early pathogenic events in
      fetal SMA spinal cord.
AB  - We investigated the expression of choline acetyltransferase, a specific marker
      for cholinergic neurons, in control and spinal muscular atrophy fetuses and
      newborns. By immunoblot we observed at 12 and 15 weeks a similar pattern of
      choline acetyltransferase expression in spinal muscular atrophy with respect to
      controls, although at 22 weeks this expression was reduced, probably due to a
      smaller number of motor neurons in the spinal muscular atrophy spinal cord. By
      immunohistochemistry, the counting of positive and negative motor neurons for
      choline acetyltransferase immunostaining in control and spinal muscular atrophy
      fetuses showed a similar proportion at all stages analyzed. The choline
      acetyltransferase-negative motor neurons were of similar appearance in both
      groups. After birth, chromatolytic motor neurons were detected in spinal muscular
      atrophy, all of which were choline acetyltransferase-negative. Our results in
      spinal muscular atrophy fetuses indicate that choline acetyltransferase
      immunostaining does not identify early events in neuronal pathogenesis and
      suggest that the spinal muscular atrophy surviving motor neurons may not be
      dysfunctional during this period. Furthermore, spinal muscular atrophy choline
      acetyltransferase-negative motor neurons showed detectable pathological changes
      only after birth, indicating that choline acetyltransferase is a late marker for
      motor neuron degeneration and not a primary contributing factor in this process.

PMID- 15725588
TI  - Recurrent syncope as persistently isolated feature of transthyretin amyloidotic
      polyneuropathy.
AB  - In transthyretin familial amyloid polyneuropathy (TTR-FAP), single clinical
      features rarely remain isolated and are usually accompanied by other symptoms. We
      describe a patient with TTR-FAP, who had recurrent episodes of syncope for 4
      years as an overt and isolated symptom. Later, he experienced paresthesia in the
      hands, and impotence. Molecular analysis of the TTR gene revealed a Thr49Ala
      mutation. The unusual clinical presentation presents a diagnostic challenge.

PMID- 15725589
TI  - Oculopharyngeal muscular dystrophy with PABPN1 mutation in a Chinese Malaysian
      woman.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder of
      middle age presenting as progressive dysphagia and eyelid ptosis, due to short
      expansions of the GCG trinucleotide repeat (from GCG6 to GCG8-13) in the
      polyadenylate binding-protein nuclear 1 (PABPN1) gene. OPMD is rarely seen in
      Asians and morphologically and/or genetically confirmed cases have been reported
      in Japanese kindreds only. We report a 64 year old Chinese-Malaysian woman who
      presented with progressive dysphagia and bilateral ptosis for about 6 years. Her
      mother and elder brother (both deceased) were believed to be affected. Muscle
      histopathology revealed angulated fibres with rimmed vacuoles. Genetic analysis
      showed repeat expansion in one allele to (GCG)9 while normal in the other (GCG)6.
      This is the first non-Japanese Asian family with genetically confirmed OPMD.

PMID- 15725590
TI  - Bioeffects of moderate-intensity static magnetic fields on cell cultures.
AB  - The interaction of static magnetic fields (SMFs) with living organisms is a
      rapidly growing field of investigation. However, despite the increasing number of
      studies on the effects of the interaction of SMFs with living organisms, many
      gaps in our knowledge still remain. One reason why it is extremely important to
      deeply understand the true mode of action of MFs on living organisms, is the need
      to protect human health in consideration of the probable future introduction of
      new technologies such as magnetically levitated trains and the therapeutical use
      of MFs (e.g. magnetic resonance imaging, MRI, coupling of MF exposure with
      chemotherapy). The lack of knowledge of the morphological modifications brought
      about by exposure to moderate-intensity SMFs prompted us to investigate the
      bioeffects of 6mT SMFs on different cell types, by means of light and electron
      microscopy, confocal laser scanning microscopy and immuno- or cytochemistry. In
      the present article we report our own and other data from the literature on the
      morphological studies of the bioeffects of moderate-intensity SMFs. We focus on
      morphological modifications related to cell shape, cell surface, cytoskeleton,
      and plasma membrane expression of molecules and carbohydrate residues. The
      effects of exposure to moderate-intensity SMF for 24 or 48 h, on apoptosis, on
      apoptotic related gene products, on macrophagic differentiation and on
      phagocytosis of apoptotic cells in primary cell cultures (transformed or
      stabilized cell lines) will be also discussed. Moderate-intensity (6mT) SMFs
      induced modifications of cell shape, cell surface and cytoskeleton, progressively
      achieved during the entire period of exposure. In general, at the end of the
      exposure period, the cells had a less flat shape due to partial detachment from
      the culture dishes or a more round-elongated shape (in relation to adhesion
      growth or in suspension growth respectively) with many irregular lamellar
      microvilli, while the morphology of the organelles remained unmodified. In
      parallel with cell shape changes, the microfilaments and microtubules, as well as
      the quantity and distribution of surface ConA-FITC and Ricinus Comm.-FITC
      labelling sites, were modified in a time-dependent manner. Apoptosis was
      influenced in a cell type-dependent manner: for some cells spontaneous apoptosis
      decreased while, for others, it increased to about 20% after 24h of continuous
      exposure. The induction of apoptosis was likely due to the increment of [Ca(2+)]i
      during exposure. Cell proliferation was only slightly affected. Indeed, in
      addition to the cell type, the time of exposure was also an important factor in
      the intensity of the effects produced. Both apoptotic rate and cell and surface
      shape were influenced by exposure to SMFs when simultaneously administered with
      apoptogenic drugs. Apoptotic cells were cleared by an efficient and fast process
      of phagocytosis mediated by specific epitopes, externalized during the formation
      of the apoptotic cells, on the dead cells and by specific receptors on the
      phagocytes (both "professional" and "nonprofessional"). The recognition of
      apoptotic lymphocytes as well as of control cells exposed for at least 24h to 6mT
      SMF by liver sinusoidal cells was influenced by the cell surface modifications
      which both apoptotic or normal exposed cells underwent during the induction of
      apoptosis or SMF exposure. The degree of macrophagic differentiation of human pro
      monocytic U937 cells induced by phorbol ester was decreased by exposure to 6mT
      SMFs, with a consequent fall in cell adhesion and increased polarization of
      pseudopodia and cytoplasmic protrusions. Differentiation alone, or in combination
      with exposure to SMFs, affects distribution and quantity of cell surface
      carbohydrate residues, surface expression of markers of macrophage
      differentiation, and phagocytic capability. The increasing amount of data
      reporting on the bioeffects of SMFs is leading researchers to an understanding of
      how important it is to fully understand the mode of action of MFs on living
      organisms. Indeed, even if the perturbations of biological systems by SMFs are
      sublethal at shorter times of exposure, these perturbations could, especially at
      longer times of exposure, evolve into a progressive accumulation of
      modifications, whose ultimate effects still need to be clarified.

PMID- 15725591
TI  - Atomic resolution STEM analysis of defects and interfaces in ceramic materials.
AB  - Atomic resolution scanning transmission electron microscopy (STEM) analysis, in
      particular the combination of Z-contrast imaging and electron energy-loss
      spectroscopy (EELS) has been successfully used to measure the atomic and
      electronic structure of materials with sub-nanometer spatial resolution.
      Furthermore, the combination of this incoherent imaging technique with EELS
      allows us to correlate certain structural features, such as defects or interfaces
      directly with the measured changes in the local electronic fine-structure. In
      this review, we will discuss the experimental procedures for achieving high
      resolution Z-contrast imaging and EELS. We will describe the alignment and
      experimental setup for high-resolution STEM analysis and also describe some of
      our recent results where the combined use of atomic-resolution Z-contrast imaging
      and column-by-column EELS has helped solve important materials science problems.

PMID- 15725592
TI  - Atomic scale characterization of the Pt/TiO2 interface.
AB  - We present results from an investigation of the Pt/TiO(2) catalyst system using a
      combination of Z-contrast imaging and electron energy loss spectroscopy (EELS) in
      the scanning transmission electron microscope. Evidence of a strong interaction
      between the Pt particles and the support is found to be dependent on the Pt
      cluster size, being manifested either as an encapsulation of the Pt particles by
      the support or a distortion of the structure of the Pt particles. In the case of
      clusters that are only a few atoms in size, we show direct evidence of an
      epitaxial nucleation relationship between Pt and Titania. The results also show
      unexpectedly that Pt particles exhibit a preferential nucleation on rutile rather
      than anatase.

PMID- 15725593
TI  - Chromosomal location polymorphism of major rDNA sites in two Mediterranean
      populations of the killifish Aphanius fasciatus (Pisces: Cyprinodontidae).
AB  - The chromosomes of the Mediterranean killifish, Aphanius fasciatus from two
      populations, the Lagoon of Venice (LV, 15 specimens) and the Lagoon "Stagnone di
      Marsala" (Sicily) (SM, 48 specimens), have been investigated using conventional
      Ag-staining and fluorescent in situ hybridization (FISH) with 18S rDNA probe. The
      two methods revealed variation in the number of major rDNA sites ranging from 8
      to 14 (LV) and from 1 to 4 (SM) per individual. The fact that each individual
      possessed its own number of sites implies that observed variation was structural.
      Moreover, overlapping of silver staining and FISH patterns demonstrated that all
      ribosomal genes were transcriptionally active in each specimen.

PMID- 15725594
TI  - Distribution of molecularly imprinted polymer layers on macroporous silica gel
      particles by STEM and EDX.
AB  - Using transmission electron microscopy (TEM) in parallel and scanning mode (STEM)
      combined with energy dispersive X-ray spectroscopy (EDX) the distribution of
      molecularly imprinted polymer layers covalently grafted on the inner and outer
      surface of macroporous silica gel particles was observed. The grafting was
      achieved using a special initiator system (iniferter) and applied on a well known
      model system producing molecularly imprinted layers with L-phenyl alanine analide
      (L-PA) as template. By staining the sample with RuO(4) before its embedment in
      epoxy resin and cutting ultra thin slices it was possible to identify the stained
      grafted polymer on the silica matrix by EDX. Based on this, complete particle
      slices could be investigated by visual means according to the presence or absence
      of grafted polymer and its layer homogeneity.

PMID- 15725595
TI  - Maple syrup urine disease hair reveals the importance of 18-methyleicosanoic acid
      in cuticular delamination.
AB  - 18-Methyleicosanoic acid (18-MEA) is thought to be covalently bound to the outer
      surface of human hair and is a major component of the outer beta-layer of the
      cuticular cell membrane complex (CCMC). Cuticular delamination, whether this
      occurs between the outer beta- and delta-layers or within the plane of the beta
      layer, results in a fresh layer of 18-MEA being exposed at the newly-revealed
      surface. Hair from patients with Maple Syrup Urine Disease (MSUD), however, does
      not contain 18-MEA and here, we report on the importance this unusual fatty acid
      in cuticular delamination. Hair fibres were collected from 10 patients with
      classic (type 1A) MSUD from a Mennonite community in Pennsylvania, USA. Included
      amongst these were hairs from dizygotic twins (A1 and A2), one of whom had MSUD,
      and the other did not; it was unknown at the beginning of the study which twin
      had MSUD. The outer surfaces were examined using atomic force microscopy (AFM)
      and transverse sections imaged using transmission electron microscopy (TEM). The
      newly revealed intercellular surface regions from twin A2 were found to be
      significantly rougher than those from twin A1. TEM studies showed the trilamellar
      CCMC to be continuous for twin A1, but possessed discontinuities of variable
      length (100-1000 nm) for twin A2. In contrast with other work, TEM showed no
      specific defects in the outer beta-layer. The outer cuticular surfaces for most
      MSUD patients showed a great abundance of residual endocuticle, although in other
      cases this was less pronounced. These differences may be explained by some
      residual activity of the branched-chain alpha-ketoacid (BCKD) dehydrogenase.
      Cuticular delamination in MSUD-hair probably still occurs within the general
      plane of the CCMC, although fracture through discontinuities of this layer
      results in zones of endocuticle being exposed at the new surface.

PMID- 15725596
TI  - Scanning electron microscopy investigation of Cu-TCNQ micro/nanostructures
      synthesized via vapor-induced reaction method.
AB  - Micro/nanostructures based on the metal-organic complex Cu-TCNQ were successfully
      synthesized by a novel method: vapor-induced reaction. Scanning electron
      microscopy was used to investigate the morphology on the three different parts of
      the substrate: the hot reaction area, a transitional reaction area and an induced
      reaction area. The results show that the morphology of the as-grown structures
      evolves from microstructures to nanostructures. The formation mechanism of these
      different structures may be understood from electrochemical principles and the
      decreasing concentration of TCNQ.

PMID- 15725597
TI  - Radiation damage analysis of 7,7,8,8,-tetracyanoquinodimethane (TCNQ) and
      2,3,5,6,-tetrafluoro-7,7,8,8,-tetracyanoquinodimethane (F4TCNQ) by electron
      diffraction and electron energy loss spectroscopy.
AB  - The electron irradiation sensitivity is compared between TCNQ and F(4)TCNQ. The
      characteristic doses, D(1/e), determined by the attenuation of the diffraction
      intensities are 0.08-0.11Ccm(-2) for TCNQ, and 0.04-0.06Ccm(-2) for F(4)TCNQ,
      respectively. It is found that F(4)TCNQ is more sensitive to radiation damage
      than TCNQ in spite of the substitution of hydrogen with fluorine. From electron
      energy-loss spectroscopy (EELS), it is found that the damaging process for the
      two materials begins in a similar way, as seen from mass loss and spectrum
      changes observed for doses which exceed the characteristic dose. Although
      sensitive to the sample orientation, the carbon K-edge fine structures of TCNQ
      are almost preserved below the critical dose. Theoretical calculation predicts
      that the scission of hydrogen contributes to the spectrum shape very little
      compared to nitrogen scission. Beyond the characteristic dose, fluorine loss from
      F(4)TCNQ occurs faster than nitrogen loss but little loss of carbon is observed.
      In a similar way, nitrogen loss from TCNQ occurs beyond the characteristic dose,
      while carbon appears constant. From detailed analysis of the carbon and nitrogen
      K-edge fine structures of TCNQ and F(4)TCNQ, it is found that the pi* peak of
      nitrogen in TCNQ decreases below the characteristic dose, while pi* loss of
      nitrogen in F(4)TCNQ, and pi* loss and sigma* increase of carbon in both
      materials are observed beyond the characteristic dose. The changes in the fine
      structures are believed to be due to the chemical alteration such as cross
      linking, in which the pi-bonding system of nitrogen or carbon turns into sigma
      bonding. The difference in characteristic dose between TCNQ and F(4)TCNQ is
      explained by considering "effective molecular occupancy", where F(4)TCNQ has a
      larger intermolecular empty space than TCNQ.

PMID- 15725598
TI  - Preparation of GaN-based cross-sectional TEM specimens by laser lift-off.
AB  - Laser lift-off (LLO) technology is successfully used to prepare GaN-based TEM
      cross-sectional specimens. Detailed procedures of the method to prepare the
      specimens are demonstrated. Large thin areas suitable for TEM analysis were
      obtained. TEM images of the resulting GaN interface are studied, and the changes
      in structural quality are confined to approximately the first 250 nm of the
      epilayer. Clear TEM images of the whole epilayer and the InGaN quantum wells and
      the HRTEM images of the superlattice layer are demonstrated, showing that LLO is
      a quick and ideal method to study the crystal structure of the epilayer,
      especially if only the upper layers are of interest.

PMID- 15725599
TI  - Microscopy investigation of Ag-TCNQ micro/nanostructures synthesized via two
      solution routes.
AB  - The micro/nanostructures of metal-organic complex Ag-TCNQ were successfully
      synthesized by the reaction between Ag film and TCNQ dissolved in acetonitrile
      via two solution routes, i.e. immerging and dipping reaction. X-ray diffraction
      confirmed that the obtained Ag-TCNQ micro/nanostructures were crystalline. The
      morphology of the as-grown structures varied from straight nanowires and
      microtubes to complex fractals and dendrites. The growth mechanism of the mainly
      dendrites may be considered within the framework of DLA model.

PMID- 15725600
TI  - Increased incidence of micronuclei assessed with the micronucleus assay and the
      fluorescence in situ hybridization (FISH) technique in peripheral blood
      lymphocytes of nurses exposed to nitrous oxide.
AB  - It has been postulated that exposure to nitrous oxide and halogenated
      anaesthetics is associated with various adverse health effects such as
      neurological and reproductive abnormalities or impairment of hepatic functions.
      In spite of the quite well known genotoxic effects of exposure to nitrous oxide
      in vivo, the mechanisms of these effects are still not clear. The aim of this
      study was to assess the frequency of micronuclei and to identify the type of
      chromosomal damage (clastogenic or aneugenic) in peripheral blood lymphocytes of
      operating-room nurses exposed to nitrous oxide. The study group comprised 46
      women working at departments where the concentration of nitrous oxide ranged from
      14 to 2308 mg/m3. The control population was composed of 28 women employed in the
      same hospitals but in non-surgical departments. The clastogenic/aneugenic effect
      of nitrous oxide was evaluated in lymphocytes using the standard micronucleus
      (MN) assay in combination with the fluorescence in situ hybridization (FISH)
      technique with pancentromeric probes. The results show a significant increase of
      the MN frequency in lymphocytes of exposed nurses compared with the control group
      (4.36+/-2.23 versus 9.02+/-4.67). The multiple regression analysis revealed a
      statistically significant relationship (p=0.0009) between MN frequency and
      exposure status, indicating that the level of exposure was the main factor
      affecting chromosomal damage. As assessed by FISH analysis, the overall
      frequencies of centromere-positive MN in the control and exposed groups were 43
      and 49%, respectively. The increase observed in the exposed group may suggest a
      slight, statistically insignificant pro-aneugenic effect of exposure to nitrous
      oxide.

PMID- 15725601
TI  - DNA damage measured by the single-cell gel electrophoresis (Comet) assay in
      mammals fed with mussels contaminated by the 'Erika' oil-spill.
AB  - This research aimed to estimate potential genotoxicity for consumers resulting
      from the ingestion of seafood contaminated with polycyclic aromatic hydrocarbons
      (PAHs) released into the marine environment after the 'Erika' shipwreck along the
      coasts of south Brittany, in France. Mussels (Mytilus sp.) collected from sites
      on the Atlantic coast that were affected by the oil slick in various degrees,
      were used to feed rats daily for 2 and 4 weeks. DNA damage was measured by use of
      the Comet assay in the liver, bone marrow and blood of rats receiving food
      contaminated with 312 microg of 16PAHs/kg dry weight (d.w.) equivalent to 33.8
      microg TEQs (toxic equivalent quantities to benzo(a)pyrene (BaP))/kg d.w.
      mussels, 569 microg/kg d.w. (83.6 microg TEQs/kg) and 870 microg/kg d.w. (180.7
      microg TEQs/kg). A dose-effect-time relationship was observed between the amount
      of DNA damage in the liver and bone marrow of the rats and the PAH contamination
      level of the mussels. Genotoxicity increased during the period between 15 and 30
      days in rats that received food at the highest two PAH levels. On the other hand,
      no significant change in liver and bone marrow of rats fed with mussels
      containing 33.8 microg TEQs/kg d.w. was recorded at 30 days compared with 15
      days, indicating efficient DNA repair capacity at low levels of exposure. No
      signs of genotoxicity were found in peripheral blood. Globally, the observed
      effects were rather moderate. These results show that oil-contaminated food
      caused DNA damage in predators, and underline the bioavailability to consumers of
      pollutants in mussels contaminated with fuel oil. The usefulness of the Comet
      assay as a sensitive tool in biomonitoring studies analyzing responses of PAH
      transfer through food webs was also confirmed.

PMID- 15725603
TI  - Antioxidant and genotoxic properties of South African herbal extracts.
AB  - This study investigated the antioxidant and genotoxic properties of 13 South
      African herbal extracts. Results from the single-cell gel electrophoresis (Comet)
      assay indicated that there were profound differences between the plant extracts
      in their ability to produce DNA damage, which varied from highly genotoxic to
      protective. Similarly, water and methanol extracts of all the herbal preparations
      showed variable potencies in scavenging hydroxyl radicals, as measured by means
      of electron spin resonance spectrometery (ESR) with the spin trap alpha-phenyl-N
      tert-butylnitrone (PBN). In general, methanol extracts were better scavengers of
      hydroxyl radicals than the corresponding water extracts. This was also true of
      the ability of these extracts to inhibit membrane lipid peroxidation, assessed
      with diphenyl-1-pyrenylphosphine (DPPP). However, neither methanol nor water
      extracts had the ability to protect against DNA damage. The results show that
      further research on South African traditional herbal extracts is imperative to
      gain understanding of the mechanisms involved in their pharmacological effects.
      The tests implemented in the present investigation are recommended for screening
      other herbal extracts.

PMID- 15725602
TI  - Structure-activity considerations and in vitro approaches to assess the
      genotoxicity of 19 methane-, benzene- and toluenesulfonic acid esters.
AB  - Sulfonic acid esters are considered as potentially alkylating agents that may
      exert genotoxic effects in bacterial and mammalian cell systems. One possible
      source of human exposure stems from drug synthesis when the salt-forming agents
      methanesulfonic acid, benzenesulfonic acid or p-toluenesulfonic acid are used
      together with alcoholic solvents such as methanol, ethanol and propanol. In this
      study computer-assisted structural considerations and in vitro approaches (Ames
      mutagenicity test using Salmonella typhimurium strains TA98 and TA100, and the
      micronucleus test using L5178Y mouse lymphoma cells) were used to assess the
      genotoxic properties of 19 sulfonic esters. While all esters may be principally
      active as genotoxicants based on the presence of the sulfonate moiety, the
      statistical correlative multiple computer automated structure evaluation (MCASE)
      system (MC4PC version 1.0) using the Ames mutagenicity A2I module (version 1.54),
      rank-ordered the activity of the benzenesulfonic acid esters in the Ames test
      negligible due to an inactivating modulator and a deactivating fragment, whereas
      the methane- and toluenesulfonic acid esters were predicted to be positive in
      this test. In the Ames test, with the exception of the p-toluenesulfonic acid
      ethyl and iso-butyl esters, all compounds came out positive in Salmonella strain
      TA100. Methanesulfonic iso-propyl, sec-butyl and benzenesulfonic acid iso-propyl
      ester also showed mutagenic potential in strain TA98. In general, differences
      between results seen in Ames tests performed with or without metabolic activation
      were rather small. In L5178Y mouse lymphoma cells, benzenesulfonic acid n- and
      iso-butyl ester and p-toluenesulfonic acid iso-butyl ester did not increase the
      number of cells containing micronuclei. The other esters were positive in this
      micronucleus test; however, methanesulfonic acid iso-butyl ester was found to be
      only weakly positive at excessively cytotoxic concentrations. These compounds
      were generally found to be more potent with regard to micronucleus induction when
      tested without metabolic activation (20 h treatment). In conclusion, the iso
      propyl esters of the three sulfonic acids under study were found to be the
      strongest mutagens, either when tested in the Ames test or the micronucleus
      assay, whereas p-toluenesulfonic acid iso-butyl ester was the only compound shown
      to be devoid of a genotoxic potential in both tests.

PMID- 15725605
TI  - Specific plant DNA adducts as molecular biomarkers of genotoxic atmospheric
      environments.
AB  - The general purpose of this study was to determine whether the formation of DNA
      addition products ('adducts') in plants could be a valuable biomarker of
      genotoxic air pollution. Plants from several species were exposed to ambient
      atmosphere at urban and suburban sites representative of different environmental
      conditions. The levels of NO2 and of the quantitatively major genotoxic air
      pollutants benzene, toluene, and xylene were monitored in parallel with plant
      exposure. DNA adducts were measured in bean (Phaseolus vulgaris), rye-grass
      (Lolium perenne), and tobacco (Nicotiana tabacum) seedlings by means of the [32P]
      postlabeling method. Whereas, no correlation was found between the levels of the
      major genotoxic air pollutants and the total amounts of DNA adducts, individual
      analyses revealed site-specific and plant species-specific adduct responses, both
      at the qualitative and quantitative level. Among these, the amount of a specific
      rye-grass DNA adduct (rgs1) correlated with benzene/toluene/xylene levels above a
      threshold. For further characterization, rye-grass seedlings were treated in
      controlled conditions with benzene, toluene, xylene or their derivatives. On the
      other hand, in vitro DNA adduct formation assays were developed involving
      benzene, toluene, xylene, or their derivatives, and plant microsomes or purified
      peroxidase. Although in some cases, these approaches produced specific adduct
      responses, they failed to generate the rgs1 DNA adduct, which appeared to be
      characteristic for on-site test-plant exposure. Our studies have thus identified
      an interesting candidate for further analysis of environmental biomarkers of
      genotoxicity.

PMID- 15725604
TI  - The effects of thyme volatiles on the induction of DNA damage by the heterocyclic
      amine IQ and mitomycin C.
AB  - The leafy parts of thyme and its essential oil have been used in foods for its
      flavour, aroma and preservation for many years. In the present study the
      genotoxic potential of major compounds of thyme oil, i.e. thymol, carvacrol, and
      gamma-terpinene and of the methanolic extracts of thyme, were investigated in
      human lymphocytes by single-cell gel electrophoresis. Also, the effects of these
      substances on the induction of DNA damage by 2-amino-3-methylimidazo[4,5-f]
      quinoline (IQ) and mitomycin C (MMC) were evaluated. No increase in DNA strand
      breakage was observed at thymol and gamma-terpinene concentrations below 0.1 mM,
      but at the higher concentration of 0.2 mM significant increases in DNA damage
      were seen. Thymol and gamma-terpinene significantly reduced the DNA strand
      breakage induced by IQ and MMC at the lower concentrations studied. Carvacrol,
      which is an isomer of thymol, seemed to protect lymphocytes from the genotoxic
      effects of IQ and MMC at non-toxic concentrations below 0.05 mM, but at the
      higher concentration of 0.1 mM carvacrol itself induced DNA damage. Also the
      constituents of the n-hexane and ethyl acetate fractions prepared from the
      concentrated aqueous methanolic extracts of Thymus spicata protected lymphocytes
      against IQ- and MMC-induced DNA damage in a concentration-dependent manner.

PMID- 15725606
TI  - Microsatellite mutations show no increases in the children of the Chernobyl
      liquidators.
AB  - We performed a study on Belarusian "liquidators", exploring whether increase in
      the frequencies of germline mutations at microsatellite loci could be found in
      their progeny. The liquidators, mostly young males, were those involved (during
      1986 and 1987) in clean-up operations in the radioactively contaminated area
      following the Chernobyl nuclear power plant accident in 1986. Many liquidators
      fathered children during the clean-up period and after the work had been
      terminated. The numbers of families studied were 64 (liquidators) and 66
      (controls). A total of 72 loci (31 autosomal, one X-linked and 40 Y-linked) were
      used. DNA was isolated from peripheral blood lymphocytes and the microsatellite
      loci were amplified by the polymerase chain reaction with fluorescence-labelled
      primers. Mutations were detected as variations in the length of the loci. At the
      Y-linked loci, the mutation rates (expressed as number of mutations among the
      total number of loci for the individuals included) are 2.9 x 10(-3) (4/1392) and
      2.1 x 10(-3) (3/1458) in the children of exposed and control parents,
      respectively. This difference is not statistically significant. At the autosomal
      loci, the corresponding estimates are 5.9 x 10(-3) (11/1862; exposed group) and
      8.5 x 10(-3) (18/2108; control). Again, the difference is not significant. The
      possibility that the Belarusian population might have been unexpectedly exposed
      to some chemical contaminants in the environment appears unlikely in view of the
      finding that the spontaneous mutation rates at the same set of loci in several
      non-Belarusian populations were similar to those in Belarus. The estimated mean
      radiation dose to the liquidators was small, being about 39 mSv, and this might
      be one reason why no increases in mutation rates due to radiation could be found.

PMID- 15725607
TI  - DNA-protein cross-links and sister chromatid exchanges induced by dimethylarsinic
      acid in human fibroblasts cells.
AB  - Biotransformation of inorganic arsenic to form both methylarsinic acid (MA) and
      dimethylarsinic acid (DMA) has traditionally been considered as a mechanism to
      facilitate the detoxification and excretion of arsenic. However, the methylation
      of inorganic arsenic as a detoxification mechanism has been questioned due to
      recent studies revealing an important role of organic arsenic in the induction of
      genetic damage. In a previous report a reduction of DNA migration after treatment
      of cells with DMA was described. In order to further evaluate the possible
      induction of protein-DNA adducts, an experiment was performed taking into account
      other parameters and modifications of the standard alkaline comet assay. In
      addition, the results obtained with the comet assay were compared with those
      obtained by analyzing the induction of sister chromatid exchanges (SCEs). SCE
      frequencies were significantly increased in treated cells in relation to controls
      (p<0.001). Furthermore, in the standard alkaline comet assay, as well as in the
      control assay for proteinase K treatment, a significant dose-dependent reduction
      in tail moment was observed. Nevertheless, the post-treatment with proteinase K
      induced the release of proteins joined to the DNA and consequently, a dose
      dependent increment in DNA migration was observed (p<0.001). These results
      suggest that DNA-protein cross-links may be an important genotoxic effect induced
      by dimethylarsinic acid in human MRC-5 cells.

PMID- 15725608
TI  - Direct-acting mutagenicity of extracts of coal burning-derived particulates and
      contribution of nitropolycyclic aromatic hydrocarbons.
AB  - Benzene-ethanol extracts from particulates produced by coal burning were
      separated into four fractions by silica-gel column chromatography using n-hexane
      (240 ml), n-hexane-dichloromethane (3:1, v/v) (200 ml), dichloromethane (200 ml)
      and methanol (450 ml), as the corresponding eluents. The mutagenicity of each
      fraction was assayed by the Ames test using the Salmonellatyphimurium YG1024
      strain. The nitropolycyclic aromatic hydrocarbons (NPAHs) of each fraction were
      assayed by high-performance liquid chromatography with chemiluminescence
      detection. The highest activity was observed in the n-hexane-dichloromethane
      fraction (Fr. 2). The mutagenic contribution of this fraction was 69.9% of the
      total of the four fractions. Ten of 11 NPAHs detected were in Fr. 2 and one (1
      nitropyrene) was most concentrated in Fr. 3. Among the NPAHs examined, 3
      nitrobenzanthrone made the largest mutagenic contribution. This is the first
      report of detection of 3-nitrobenzanthrone in coal burning-derived particulates.

PMID- 15725609
TI  - Effects of N-acetyl transferase 1 and 2 polymorphisms on bladder cancer risk in
      Caucasians.
AB  - Cigarette smoking is the predominant risk factor for bladder cancer (BC). Major
      carcinogens present in tobacco smoke include a number of aromatic and
      heterocyclic amines. Two distinct N-acetyl transferase (NAT) enzymes, NAT1 and
      NAT2, play important roles in the bio-activation and detoxification of these
      carcinogens. Genes encoding NAT1 and NAT2 are highly polymorphic among human
      populations, and these polymorphisms result in rapid or slow acetylator
      phenotypes. Recent studies have suggested that variant alleles leading to slow
      acetylation by the NAT2 enzyme or rapid acetylation by the NAT1 enzyme constitute
      possible risk factors for bladder cancer. In this case-control study, we sought
      to determine whether NAT1 and NAT2 polymorphisms are associated with bladder
      cancer risk in the largest sample size to date. PCR-RFLP assay was used to
      determine the presence of NAT1 and NAT2 polymorphisms in 507 Caucasian BC
      patients and 513 age-, gender-, and ethnicity-matched healthy controls. Overall,
      we found no significant association between BC risk and NAT1 NAT1*10 allele
      (OR=0.95; 95% CI 0.73-1.25). However, our data suggested that NAT2 slow
      acetylator genotypes were associated with a significant increased risk of BC
      (OR=1.31; 95% CI, 1.01-1.70). This elevated risk appeared more evident in older
      individuals (OR=1.41; 95% CI, 1.01-1.98) than in younger individuals (OR=1.15;
      95% CI, 0.76-1.74). Moreover, the risk was greater for heavy smokers (OR=2.11;
      95% CI, 1.33-3.35) than light smokers (OR=0.96; 95% CI, 0.61-1.53) and never
      smokers (OR=1.23; 95% CI, 0.79-1.90). Finally, a joint effect between NAT2 slow
      acetylators and heavy smokers was observed. Using never smokers with NAT2 rapid
      acetylator genotypes as a reference group, heavy smokers with NAT2 slow
      acetylator genotypes showed an over six-fold increase in BC risk. In a
      multiplicative interaction model, the interaction term was statistically
      significant (P=0.02). Our data suggest that having a NAT2 slow acetylator
      genotype is a significant risk factor for BC, particularly in smokers and older
      individuals.

PMID- 15725610
TI  - Assessment of DNA damage in peripheral blood of heavy smokers with the comet
      assay and the micronucleus test.
AB  - The comet assay (single-cell gel electrophoresis, SCG) is being increasingly used
      in human biomonitoring for the detection of genotoxic exposures. Cigarette
      smoking is a well-documented source of a variety of potentially mutagenic and
      carcinogenic compounds. Therefore, smoking should represent a relevant mutagenic
      exposure and lead to genotoxic effects in exposed cells. However, our previous
      investigations as well as several other published studies on human biomonitoring
      failed to show an effect of smoking on DNA migration in the comet assay, while
      some other studies did indicate such an effect. Although many factors can
      contribute to the generation of discrepant results in such studies, clear effects
      should be obtained after high exposure. We therefore performed a comparative
      study with healthy male heavy smokers (>20 cigarettes per day) and non-smokers
      (n=12 in each group). We measured the baseline comet assay effects in fresh whole
      blood samples and isolated lymphocytes. In addition, the amount of
      'formamidopyrimidine DNA-glycosylase (FPG)-sensitive sites' was determined by a
      combination of the standard comet assay with the bacterial FPG protein.
      Furthermore, the influence of a repair inhibitor (aphidicolin, APC) on baseline
      DNA damage was comparatively analysed. Duplicate slides from each sample were
      processed and analysed separately. In all experiments, a reference standard
      (untreated V79 cells) was included to correct for assay variability. Finally, to
      compare the comet assay results with another genetic endpoint, all blood samples
      were investigated in parallel by the micronucleus test (MNT). Baseline and gamma
      radiation-induced micronucleus frequencies were determined. None of these
      approaches revealed a significant difference between heavy smokers and non
      smokers with regard to a genotoxic effect in peripheral blood cells.

PMID- 15725611
TI  - CP-arene oxides: the ultimate, active mutagenic forms of cyclopenta-fused
      polycyclic aromatic hydrocarbons (CP-PAHs).
AB  - The bacterial mutagenic response (Ames-assay, Salmonella typhimurium strain
      TA98+/-S9-mix) of a series of monocyclopenta-fused polycyclic aromatic
      hydrocarbons (CP-PAHs) identified in combustion exhausts, viz.
      cyclopenta[cd]pyrene (1), acephenanthrylene (2), aceanthrylene (3) and
      cyclopenta[hi]chrysene (4), is re-evaluated. The mutagenic effects are compared
      with those exerted by the corresponding partially hydrogenated derivatives, 3,4
      dihydrocyclopenta[cd]pyrene (5), 4,5-dihydroacephenanthrylene (6), 1,2
      dihydroaceanthrylene (7) and 4,5-dihydrocyclopenta[hi]chrysene (8). It is shown
      that the olefinic bond of the externally fused five-membered ring of 1, 3 and 4
      is of importance for a positive mutagenic response. In contrast, whilst CP-PAH 2
      is found inactive, its dihydro analogue (6) shows a weak metabolism-dependent
      response. The importance of epoxide formation at the external olefinic bond in
      the five-membered ring is substantiated by the bacterial mutagenic response of
      independently synthesized cyclopenta[cd]pyrene-3,4-epoxide (9), acephenanthrylene
      4,5-epoxide (10), aceanthrylene-1,2-epoxide (11) and cyclopenta[hi]chrysene-4,5
      epoxide (12). Their role as ultimate, active mutagenic forms, when CP-PAHs 1, 3
      and 4 exhibit a positive mutagenic response, is confirmed. Semi-empirical Austin
      Model 1 (AM1) calculations on the formation of the CP-arene oxides (9-12) and
      their conversion into the monohydroxy-carbocations (9a-12a and 9b-12b) via
      epoxide-ring opening support our results. For 2 and 4, which also possess a bay
      region besides an annelated cyclopenta moiety, the calculations rationalize that
      epoxidation at the olefinic bond of the cyclopenta moiety is favoured.

PMID- 15725612
TI  - Reduced clastogenic activity of maleic hydrazide in Vicia faba seedlings grown in
      a situation of overcrowding stress.
AB  - A pre-treatment stress situation of overcrowding of Vicia faba seedlings in the
      phase of germination and growth influenced their subsequent sensibility to
      treatment with the mutagenic herbicide maleic hydrazide. The seedlings showed a
      significant reduction in the frequency of micronucleated cells when they grew in
      a strongly crowded manner compared with scattered and uniformly distributed
      seedlings (3.83% versus 11.46%). The findings do not provide evidence for the
      involvement of phytochelatins in response to stress conditions in this process:
      pre-treatment with buthionine sulfoximine, a specific inhibitor of phytochelatin
      synthesis, did not modify the response of the seedlings to maleic hydrazide under
      conditions of overcrowding or under normal conditions. Scanning electron
      microscopy (SEM) was used to observe the root tip of V. faba grown in conditions
      of normal growth or overcrowding. SEM micrographs revealed differences between
      the tips with regards to root hair density and root surface morphology. Finally,
      we found a positive correlation between the frequency of micronucleated cells and
      the length of the primary root, for every time of growth considered (1, 3, 4 and
      5 days).

PMID- 15725613
TI  - Combined effects of gamma radiation and arsenite on the proteome of human TK6
      lymphoblastoid cells.
AB  - Arsenic present in drinking water and mining environments in some areas has been
      associated with an increased rate of skin and internal cancers. Contrary to the
      epidemiological evidence in humans, arsenic does not induce cancer in animal
      models, but is able to enhance the mutagenicity of other agents. In order to
      achieve a better understanding of the interaction between arsenic and ionising
      radiation, an investigation was conducted to detect differences at the proteome
      level of human TK6 lymphoblastoid cells exposed to these agents. Cells were
      exposed to either a single dose of 1-Gy 137Cs-gamma-rays or to 1 microM arsenite
      (As(III)) or to both agents in combination. Two-dimensional (2D) electrophoresis
      and matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) were
      employed for the screening and identification of proteins, respectively. It
      proved possible to identify seven proteins with significantly affected abundance,
      three of which showed increased levels and the remaining four showed decreased
      levels under at least one of the exposure conditions. Following arsenite
      treatment or irradiation, a significant increase compared with that of the
      control was observed for glutathione (GSH) transferase omega 1 and proteasome
      subunit beta type 4 precursor. The combined exposure did not result in an
      induction of the enzymes. The expression of electron-transfer flavoprotein
      subunit alpha was found to be enhanced under all three-exposure conditions.
      Ubiquinol-cytochrome C reductase complex core protein I, adenine phosphoribosyl
      transferase and endoplasmic reticulum protein hERp29 showed decreased levels
      after irradiation or arsenite treatment, but not after the combined exposure. The
      level of serine/threonine protein phosphatase 1 alpha decreased with all
      treatments. The main conclusions are that both arsenite and gamma-radiation
      influence the levels of several proteins involved in major metabolic and
      regulatory pathways, either directly or by triggering the defence mechanisms of
      the cell. The combined effect of both exposures on the level of some essential
      proteins such as glutathione transferase, proteasome or serine/threonine
      phosphatase may contribute to the co-carcinogenic effect of arsenic.

PMID- 15725614
TI  - Role of xenobiotic metabolizing gene polymorphisms in breast cancer
      susceptibility and treatment outcome.
AB  - Metabolic activation and inactivation of potential genotoxic agents occur by
      Phase I and Phase II enzymes in multiple interactions. An expanding body of
      literature demonstrates that ethnic differences in breast cancer incidence may be
      partly caused by host genetic factors particularly genetic polymorphisms of these
      carcinogen-metabolizing enzymes. The present case-control study aimed at
      identification of such low penetrance breast cancer susceptibility genes in 224
      Indian women and to investigate the potential effects of their polymorphisms on
      sporadic breast cancer risk. The main objective of the study was to evaluate the
      effects of genetic polymorphisms of the xenobiotic metabolizing genes CYP1A1,
      GSTM1 and GSTT1 on breast cancer risk by PCR-RFLP and DNA sequencing. Our results
      showed a significant association between CYP1A1 m1, m2 polymorphisms and breast
      cancer risk; however there was a lack of association between GSTM1 null deletion
      and breast cancer. The associations of CYP1A1, GSTM1 and GSTT1 genotypes with
      breast cancer risk were more pronounced among the pre-menopausal patients.
      Combined genotype analysis revealed the CYP1A1 m2 ValVal-GSTM1 homozygous null
      deletion genotype combinations to be associated with the highest risk of breast
      cancer (OR=10.3, 95% CI=1.2-86.1). Correlations with clinicopathological factors
      and treatment outcome were also analyzed for predicting disease free survival by
      univariate and multivariate analysis. Significant differences in disease free
      survival between the wild and polymorphic genotypes were observed only for CYP1A1
      m2, GSTT1 genotypes. Our results based on the analysis of functionally relevant
      polymorphisms in these low penetrance genes may provide a better model that would
      exhibit additive effects on individual susceptibility to breast cancer. Such
      genotype analysis resulting in a high-risk profile holds considerable promise for
      individualizing screening and therapeutic intervention in breast cancer. Hence,
      the present study may provide strong supportive evidence for genetic interactions
      in the etiology of breast cancer.

PMID- 15725615
TI  - Mutagenic activation of betel quid-specific N-nitrosamines catalyzed by human
      cytochrome P450 coexpressed with NADPH-cytochrome P450 reductase in Salmonella
      typhimurium YG7108.
AB  - Betel quid chewing is known to cause cheek cancer in a wide area covering Africa
      to Asia. Areca nut contained in the betel quid is believed to give rise to
      carcinogenic N-nitrosamines. In the present study, the roles of human cytochromes
      P450 (P450 or CYP) in the mutagenic activation of betel quid-specific N
      nitrosamines such as 3-(N-nitrosomethylamino)propionitrile (NMPN), 3-(N
      nitrosomethylamino)propionaldehyde (NMPA) and N-nitrosoguvacoline (NG) were
      examined by using genetically engineered Salmonella typhimurium YG7108 expressing
      each form of human P450 together with NADPH-P450 reductase, which had been
      established in our laboratory. Among typical P450s (CYP1A1, CYP1A2, CYP1B1,
      CYP2A6, CYP2A13, CYP2D6 or CYP3A4) examined, CYP2A6 was the most efficient
      activator of NMPN, followed by CYP1A1 and CYP1B1. The mutagenic activation of
      NMPN by CYP2A6 was seen at the substrate concentrations of microM levels
      (approximately 100 microM). The activation of NMPA was catalyzed predominantly by
      CYP2A13 and to lesser extents by CYP2A6, CYP1A1, CYP1A2 and CYP1B1. The
      activation of NMPA by CYP2A13 was detectable at the substrate concentrations of
      microM levels (approximately 1 microM). NG was activated by CYP2A13 and CYP2A6,
      the genotoxicity of NG being much lower than that of NMPA or NMPN. Based on these
      data, we conclude that human CYP2A subfamily members play important roles in the
      mutagenic activation of essentially all betel quid-related N-nitrosamines tested
      in the present study.

PMID- 15725616
TI  - Salicylic acid triggers genotoxic adaptation to methyl mercuric chloride and
      ethyl methane sulfonate, but not to maleic hydrazide in root meristem cells of
      Allium cepa L.
AB  - Salicylic acid (SA), 0.01 mM, a signalling phytohormone, was tested for induction
      of adaptive response against genotoxicity of methyl mercuric chloride (MMCl),
      0.013 mM; ethylmethane sulfonate (EMS), 2.5 mM, or maleic hydrazide (MH), 5 mM,
      in root meristem cells of Allium cepa. Induction of adaptive response to EMS by
      hydrogen peroxide (H2O2), 1 mM, and yet another secondary signal molecule was
      tested for comparison. Assessed by the incidence of mitoses with spindle and/or
      chromosome aberration and micronucleus, the findings provided evidence that SA
      conditioning triggered adaptive response against the genotoxic-challenges of MMCl
      and EMS, but failed to do so against MH. H2O2, which is known to induce adaptive
      response to MMCl and MH, failed to induce the same against EMS in the present
      study. The findings pointed to the possible role of signal transduction in the SA
      induced adaptive response to genotoxic stress that perhaps ruled out an
      involvement of H2O2.

PMID- 15725617
TI  - Diazepam and propofol used as anesthetics during open-heart surgery do not cause
      chromosomal aberrations in peripheral blood lymphocytes.
AB  - Diazepam is a benzodiazepine with anticonvulsant, anxiolytic, sedative and muscle
      relaxing properties. Many aspects of its toxicity have been investigated,
      including genotoxic and carcinogenic effects in various model systems. However,
      it is still unclear whether diazepam is in fact a genotoxic agent. Propofol is a
      rapid-onset, short-acting intravenous anesthetic agent. It is used widely for the
      induction and maintenance of anesthesia as well as for long-term sedation in
      intensive care units. There is limited information in the literature on its
      genotoxic effects. Both drugs are commonly used as anesthetic in patients
      undergoing open-heart surgery. Therefore, we investigated the possible genotoxic
      effects of propofol and diazepam in those patients, using a chromosomal
      aberration (CA) assay. Peripheral blood samples were collected from 45 patients
      before induction of anesthesia and at the end of the anesthesia with diazepam or
      propofol. In Group I (n=24), anesthesia was induced with 0.2 mg kg(-1) diazepam
      and 10 microg kg(-1) fentanyl. In Group II (n=21), anesthesia was induced with 1
      mg kg(-1) propofol and 10 microg kg(-1) fentanyl. Pancuronium bromide (0.1 mg kg(
      1)) was administered for skeletal muscle relaxation in both groups. Anesthesia
      was maintained by diazepam administration at 5 mg kg(-1) in Group I or by
      continuous propofol administration at 2-4 mg (kg h)(-1) in Group II. All patients
      received 0.02 mg kg(-1) pancuronium and 5 microg kg(-1) fentanyl boluses at 30-40
      min intervals for anesthesia maintenance. Body temperature was controlled during
      bypass in the two groups. We found that the mean frequency of CAs in both groups
      before and at the end of the anesthesia were not statistically significantly
      different. Our analysis also indicated that age, smoking habit and gender were
      not confounding factors. In conclusion, our results indicate that diazepam and
      propofol do not exert genotoxic effects in blood cells during open-heart surgery.

PMID- 15725619
TI  - Mutation research, genetic toxicology and environmental mutagenesis.

PMID- 15725618
TI  - Genotoxic and cytotoxic effects in the bone marrow of rats exposed to a low dose
      of paraquat via the dermal route.
AB  - The genotoxic effect of the herbicide paraquat was studied in rat bone-marrow by
      means of the micronucleus assay. Paraquat at dose levels of 6, 15 and 30 mg/kg
      body weight was given to rats in a single application via the dermal route.
      Marrow was collected at 24, 48 and 72 h after the application. The micronucleus
      assay was done as recommended by standard procedures. Paraquat gave rise to an
      increase in the number of micronuclei in a dose-dependent manner. The number of
      micronucleated polychromatic erythrocytes showed a maximum at 48 h and the
      toxicity was further prolonged, as there was no complete recovery at 72 h. These
      findings suggest a genotoxic effect of paraquat even after exposure via dermal
      application.

PMID- 15725621
TI  - The DNA Repair Interest Group: a global village.

PMID- 15725622
TI  - The Elg1 replication factor C-like complex: a novel guardian of genome stability.
AB  - The remarkable stability of the eukaryotic genome is achieved by the activity of
      many overlapping surveillance and repair mechanism. Two protein complexes with
      resemblance to replication factor C (RFC) have been recently described, that play
      important roles in maintaining the stability of the genome. These RFC-like
      complexes (RLCs) share four common subunits (Rfc2-5) and each carry a unique
      large subunit (Rad24 or Ctf18) replacing the Rfc1 subunit of the replication
      complex. Work in several laboratories has recently uncovered a novel yeast gene,
      ELG1, which seems to play a central role in keeping the genome stable. elg1
      mutants exhibit increased rates of spontaneous recombination and gross
      chromosomal rearrangements during vegetative growth. In addition, they lose
      chromosomes at an enhanced rate, show hyper-transposition of natural repeated
      elements and exhibit elongated telomeres. The Elg1 protein also associates with
      the Rfc2-5 subunits of replication factor C (RFC) to form a third RFC-like
      complex (RLC). Genetic and biochemical data indicate that the Elg1, Ctf18 and
      Rad24 RLCs work in three separate pathways important for maintaining the
      integrity of the genome and for coping with various genomic stresses. ELG1 is
      evolutionarily conserved and may play an important role in preventing the onset
      of cancer in humans. The Elg1 function is thus clearly required for maintaining
      genome stability during normal growth, and its absence has severe genetic
      consequences.

PMID- 15725623
TI  - The murine DNA glycosylase NEIL2 (mNEIL2) and human DNA polymerase beta bind
      microtubules in situ and in vitro.
AB  - 8-oxoguanine DNA glycosylase (OGG1), a major DNA repair enzyme in mammalian cells
      and a component of the base excision repair (BER) pathway, was recently shown to
      be associated with the microtubule network and the centriole at interphase and
      the spindle assembly at mitosis. In this study, we determined whether other
      participants in the BER pathway also bind microtubules in situ and in vitro.
      Purified recombinant human DNA polymerase beta (DNA Pol beta) and purified
      recombinant mNEIL2 were chemically conjugated to fluorochromes and photosensitive
      dyes and used in in situ localization and binding experiments. Results from in
      situ localization, microtubule co-precipitation and site-directed photochemical
      experiments showed that recombinant human DNA Pol beta and recombinant mNEIL2
      associated with microtubules in situ and in vitro in a manner similar to that
      shown earlier for another BER pathway component, OGG1. Observations reported in
      this study suggest that these BER pathway components are microtubule-associated
      proteins (MAPs) themselves or utilize yet to be identified MAPs to bind
      microtubules in order to regulate their intracellular trafficking and activities
      during the cell cycle.

PMID- 15725624
TI  - A recombinant exonuclease III homologue of the thermophilic archaeon
      Methanothermobacter thermautotrophicus.
AB  - AP endonucleases catalyse an important step in the base excision repair (BER)
      pathway by incising the phosphodiester backbone of damaged DNA immediately 5' to
      an abasic site. Here, we report the cloning and expression of the 774 bp Mth0212
      gene from the thermophilic archaeon Methanothermobacter thermautotrophicus, which
      codes for a putative AP endonuclease. The 30.3 kDa protein shares 30% sequence
      identity with exonuclease III (ExoIII) of Escherichia coli and 40% sequence
      identity with the human AP endonuclease Ape1. The gene was amplified from a
      culture sample and cloned into an expression vector. Using an E. coli host, the
      thermophilic protein could be produced and purified. Characterization of the
      enzymatic activity revealed strong binding and Mg2+-dependent nicking activity on
      undamaged double-stranded (ds) DNA at low ionic strength, even at temperatures
      below the optimum growth temperature of M. thermautotrophicus (65 degrees C).
      Additionally, a much faster nicking activity on AP site containing DNA was
      demonstrated. Unspecific incision of undamaged ds DNA was nearly inhibited at KCl
      concentration of approximately 0.5 M, whereas incision at AP sites was still
      complete at such salt concentrations. Nicked DNA was further degraded at
      temperatures above 50 degrees C, probably by an exonucleolytic activity of the
      enzyme, which was also found on recessed 3' ends of linearized ds DNA. The enzyme
      was active at temperatures up to 70 degrees C and, using circular dichroism
      spectroscopy, shown to denature at temperatures approaching 80 degrees C.
      Considering the high intracellular potassium ion concentration in M.
      thermautotrophicus, our results suggest that the characterized thermophilic
      enzyme acts as an AP endonuclease in vivo with similar activities as Ape1.

PMID- 15725625
TI  - Gene repair in mammalian cells is stimulated by the elongation of S phase and
      transient stalling of replication forks.
AB  - The repair of point mutations directed by modified single-stranded DNA
      oligonucleotides is dependent on the activity of proteins involved in homologous
      recombination (HR). As a consequence, factors that stimulate homologous
      recombination, such as double strand breaks, can impact the frequency with which
      repair occurs. Here, we report that the stalling of replication forks can also
      activate the gene repair pathway and lead to an enhanced level of nucleotide
      exchange. The mammalian cell line, DLD-1, containing an integrated mutant eGFP
      gene, was used as an assay system to explore how replication fork activity
      affects the overall repair reaction. The addition of 2',3'-dideoxycytidine (ddC),
      a nucleoside analog that retards the rate of elongation and effectively stalls
      the replication fork, results in a lengthened S phase and an increased number of
      gene repair events. This stimulation was reversed when caffeine was added to the
      reaction at concentrations that block the homologous recombination pathway. In
      contrast, the nucleoside analog, 1-beta-D-arabinofuranosylcytosine which stops
      replication in these cells, failed to stimulate the gene repair reaction to any
      appreciable degree until the block is released and active replication resumes.
      Furthermore, overexpression of wild-type p53 which is known to bind transiently
      to stalled replication forks blocked the stimulatory effect of ddC.
      Overexpression of mutant p53 genes, deficient in the capacity to bind DNA,
      however, did not inhibit the reaction. Our results indicate that an expansion of
      S phase and a transient stalling of replication forks can increase the frequency
      of targeted gene repair.

PMID- 15725626
TI  - Genetic network interactions among replication, repair and nuclear pore
      deficiencies in yeast.
AB  - The yeast RAD27 gene encodes a functional homolog of the mammalian FEN1 protein,
      a structure-specific endo/exonuclease which plays an important role in DNA
      replication and repair. Previous genetic interaction studies, including a
      synthetic genetic array (SGA) analysis, showed that the survival of rad27Delta
      cells requires several DNA metabolic processes, in particular those mediated by
      all members of the Rad52-dependent recombinational repair pathway. Here, we
      report the results of our SGA analysis of the collection of non-essential yeast
      genes against the rad27Delta mutation, which resulted in the identification of a
      novel synthetic lethal interaction conferred by mutations affecting the Nup84
      nuclear pore subcomplex (nup133Delta, nup120Delta and nup84Delta). Additional
      screens showed that all Rad52 group genes are required for the survival of the
      nup133Delta and nup120Delta mutants, which are defective in nuclear pore
      distribution and mRNA export, but not of the nup133DeltaN mutant, which is solely
      defective in pore distribution. This requirement for the DNA double-strand break
      (DSB) repair pathway is consistent with the observation that, like rad27Delta,
      the nup133Delta, nup120Delta and nup84Delta mutants are sensitive to methyl
      methanesulfonate (MMS). Furthermore, nup133Delta cells exhibit an increased
      number of spontaneous DNA repair foci containing Rad52. Altogether, these data
      suggest that the pathological interactions between the rad27Delta and specific
      nupDelta mutations result from the accumulation of unrepaired DNA damages.

PMID- 15725627
TI  - Transcript copy number of genes for DNA repair and translesion synthesis in
      yeast: contribution of transcription rate and mRNA stability to the steady-state
      level of each mRNA along with growth in glucose-fermentative medium.
AB  - We quantitated the copy number of mRNAs (NTG1, NTG2, OGG1, APN1, APN2, MSH2,
      MSH6, REV3, RAD30) encoding different DNA repair enzymes and translesion
      synthesis polymerases in yeast. Quantitations reported examine how the steady
      state number of each transcript is modulated in association with the growth in
      glucose-fermentative medium, and evaluate the respective contribution of the rate
      of mRNA degradation and transcription initiation to the specific mRNA level
      profile of each gene. Each transcript displayed a unique growth-related profile,
      therefore altering the relative abundance of mRNAs coding for proteins with
      similar functions, as cells proceed from exponential to stationary phase.
      Nonetheless, as general trend, they exhibited maximal levels when cells
      proliferate rapidly and minimal values when cells cease proliferation. We found
      that previous calculations on the stability of the investigated mRNAs might be
      biased, in particular regarding those that respond to heat shock stress. Overall,
      the mRNAs experienced drastic increments in their stabilities in response to
      gradual depletion of essential nutrients in the culture. However, differences
      among the mRNA stability profiles suggest a dynamic modulation rather than a
      passive process. As general rule, the investigated genes were much more
      frequently transcribed during the fermentative growth than later during the
      diauxic arrest and the stationary phase, this finding conciliating low steady
      state levels with increased mRNA stabilities. Interestingly, while the rate at
      which each gene is transcribed appeared as the only determinant of the number of
      mRNA copies at the exponential growth, later, when cell growth is arrested, the
      rate of mRNA degradation becomes also a key factor for gene expression. In short,
      our results raise the question of how important the respective contribution of
      transcription and mRNA stability mechanisms is for the steady-state profile of a
      given transcript, and how this contribution may change in response to nutrient
      availability.

PMID- 15725628
TI  - Disruption of mouse XAB2 gene involved in pre-mRNA splicing, transcription and
      transcription-coupled DNA repair results in preimplantation lethality.
AB  - The XAB2 protein (XPA-binding protein 2) with 15 tetratricopeptide repeat motifs
      has been isolated by virtue of its ability to interact with xeroderma pigmentosum
      group A (XPA) protein in the yeast two-hybrid system. It has been shown that XAB2
      interacted with Cockayne syndrome groups A and B (CSA and CSB) proteins and RNA
      polymerase II, which are known to be involved in transcription-coupled repair
      (TCR) and transcription, and that the antibodies against XAB2 protein inhibited
      the recovery of RNA synthesis after UV irradiation and normal RNA synthesis when
      microinjected into living fibroblasts. These results have indicated that XAB2 is
      involved in TCR and transcription. In this report, to elucidate the function of
      XAB2 in vivo, two types of mutations were introduced into the XAB2 gene in mice:
      a deletion of the region encompassing the promoter and exons 1-4, and a deletion
      of the C-terminal 162 amino acids. Both types of XAB2-heterozygous mice appeared
      normal physiologically and behaviorally. However, XAB2-homozygotes were
      selectively absent among the newborn mice. A detailed analysis of embryos at
      different stages of development indicated that the XAB2-homozygous mutants could
      survive until the morula stage, but could not develop to the blastocyst stage.
      These results indicate that XAB2 has an essential function in mouse
      embryogenesis.

PMID- 15725629
TI  - Alleviation of benzo[a]pyrene-diolepoxide-DNA damage in human lung carcinoma by
      glutathione S-transferase M2.
AB  - Cellular detoxification is important for the routine removal of environmental and
      dietary carcinogens. Glutathione S-transferases (GST) are major cellular phase II
      detoxification enzymes. MRC-5 cells have been found to exhibit significantly
      higher GST activity than human H1355 cells. This study investigates whether GST
      M2 activity acts as a critical determinant of the target dose of carcinogenic
      benzo[a]pyrene-diolepoxide (BPDE) and whether it has an effect on MDM2 splicing
      in the two cell lines. We used RT-PCR to clone Mu-class GST cDNA. Two forms of
      GST coming from the cell lines were characterized as GST-M2 (from MRC-5 cells)
      and GST-M4 (from H1355 cells). Nested-PCR showed that BPDE-induced MDM2 splicing
      had occurred in the H1355 cell line but not in normal MRC-5 cells. Furthermore,
      using nested-PCR and competitive ELISA, we found that in H1355 cells modified to
      stably overexpress GST-M2, splicing was abolished and BPDE adducts appeared in
      low abundance. In conclusion, exogenously overexpressed GST-M2 was effective in
      reducing BPDE-induced DNA damage in H1355 cells. The catalytic activity of GST-M2
      may play an important future role in lowering the incidence of BPDE-induced DNA
      damage.

PMID- 15725630
TI  - UBE2V2 (MMS2) is not required for effective immunoglobulin gene conversion or DNA
      damage tolerance in DT40.
AB  - The RAD6/RAD18 heterodimer promotes translesion synthesis via the
      monoubiquitination of the DNA sliding clamp, PCNA. In S. cerevisiae, a second
      complex, UBC13/MMS2/RAD5, can extend this single ubiquitin with a non-canonical
      lysine 63-linked chain. This polyubiquitination step is required for an error
      free mode of bypass, possibly template switching by the stalled replication
      complex. Evidence of a role for the human homologue of MMS2, UBE2V2, in such a
      process has been inferred from the abrogation of ultraviolet light-induced gene
      conversion following antisense knockdown of the transcript in human fibroblasts.
      To ask whether a similar mechanism contributes to abasic site-induced
      immunoglobulin gene conversion, and to ascertain the role of UBE2V2 in the
      vertebrate DNA damage response we created a ube2v2 mutant of the chicken cell
      line DT40. Unlike budding yeast mms2, ube2v2 DT40 does not exhibit significant
      hypersensitivity to DNA damage, nor the elevated sister chromatid exchange seen
      in vertebrate rad18 mutants suggesting that UBE2V2 plays a minor or redundant
      role in RAD18 dependent DNA damage tolerance. In addition, both ube2v2 and rad18
      DT40 display more or less normal levels of immunoglobulin gene conversion and,
      despite the important role played by RAD18 in DNA damage induced translesion
      synthesis, rad18 DT40, unlike rev1 DT40, does not show a defect in non-templated
      immunoglobulin gene mutation. Together these data suggest that signalling through
      PCNA ubiquitination is not required for immunoglobulin diversification in DT40.

PMID- 15725631
TI  - TAT-mediated protein transduction and targeted delivery of fusion proteins into
      mitochondria of breast cancer cells.
AB  - The protein transduction domain (PTD) from the HIV-1 TAT protein has been widely
      utilized to deliver biologically active macromolecules, including full-length
      proteins, into a variety of cell types in vitro and in vivo. Without additional
      targeting signals, the intracellular localization of the proteins delivered in
      this fashion appears to be cytoplasmic, nuclear or, as recently reported,
      endosomal. In this study, we show that the presence of the mitochondrial
      targeting signal (MTS) from hMnSOD on the N-terminus of TAT-fusion proteins
      directs them into mitochondria of breast cancer cells. We generated and purified
      fusion proteins containing GFP (MTS-GFP-TAT) or Exonuclease III (MTS-ExoIII-TAT)
      from Escherichia coli. The results of Western blots of subcellular fractions and
      fluorescent microscopic analyses revealed efficient protein transduction and
      mitochondrial localization of the fusion proteins. Specific exonuclease activity
      was found in the mitochondrial extracts isolated from MTS-ExoIII-TAT transduced
      cells. This increased exonuclease activity reduced the repair of mtDNA damage
      following oxidative stress. This diminished mtDNA repair led to a decrease in
      survival of breast cancer cells. Thus, the present study demonstrates the
      applicability of this new approach for intramitochondrial targeting of TAT-fusion
      proteins capable of modulating mitochondrial function and cell survival.

PMID- 15725633
TI  - A most important competency: professionalism. What is it?

PMID- 15725637
TI  - Cancer research training for high school and college students at a comprehensive
      cancer center.
AB  - BACKGROUND: The number of American students pursuing advanced science degree
      continues to wane. Summer research experience programs are ideal mechanisms to
      introduce high school and college students to scientific lifestyles. METHODS: A
      follow-up of participants from 1995-2003 was conducted to gauge student
      perception of the program and to measure outcomes. RESULTS: Data are presented
      from the responses of 287 (81%) participants. The Program was successful in
      recruiting female (67%) and underrepresented (>35%) students. Very high
      percentages of trainees reported pursuing advanced scientific study (>85% of high
      school and >92% college students). CONCLUSIONS: Summer research experiential
      programs can be successful in initiating or maintaining a student's interest in
      science careers.

PMID- 15725638
TI  - Evaluation of current tobacco curriculum at 12 US medical schools.
AB  - BACKGROUND: Training medical students in tobacco prevention and treatment skills
      is critical if we are to have competent physicians prepared to address the grave
      levels of morbidity and mortality associated with tobacco use. Tobacco Prevention
      and Cessation Education at US Medical Schools (PACE), a National Cancer Institute
      funded project, was launched to assess and improve curriculum content and
      teaching at 12 US medical schools. METHODS: The 2003 survey was completed by
      faculty and administrators. The survey was divided into four main sections:
      tobacco content and skills, curricular evaluation, faculty perceptions of
      barriers and promoters, and educational vision. RESULTS: Thirty-six percent of
      all medical school courses had some tobacco-related content. Five schools
      provided a total of between 4 and 8 hours of teaching, 5 schools provided 10-13
      hours, and 2 schools provided 17 and 18 hours of teaching. Of the 12 schools, 8
      had fewer hours devoted to tobacco teaching in the clerkships than during the 1st
      year courses. Only 2 schools noted any tobacco content for Obstetrics/Gynecology
      clerkships, and only 4 schools provided teaching in the pediatric setting (range
      5-201 minutes). CONCLUSION: In comparison to earlier studies, it appears that
      more tobacco content is now integrated into medical school courses. More
      improvement is necessary, however, particularly in tobacco use prevention.
      Institutions need to examine the role of faculty in prioritizing tobacco
      information and promoting a culture that builds competency in tobacco control and
      treatment.

PMID- 15725639
TI  - Teaching communication skills: an AACE survey of oncology training programs.
AB  - BACKGROUND: The extent of communication skills training (CST) in American
      oncology fellowship programs is unknown. METHODS: A survey was sent to program
      directors of medical oncology, radiation oncology, gynecologic oncology, and
      surgical oncology training programs regarding (1) the presence and method(s) of
      CST in their programs, (2) their attitude about mandatory CST, and (3) their
      attitude about a mandatory assessment of communication skills competence as a
      prerequisite for specialty certification. RESULTS: Only a third of programs
      contained some form of CST. Surgical oncology programs were particularly lacking.
      Lack of faculty time was cited as the major barrier to implementing CST. A
      majority of program directors support mandatory CST but not a core competence
      requirement for certification. CONCLUSIONS: There is a current deficiency in CST
      in American oncology fellowship training. Given the importance of communication
      skills in the provision of high-quality cancer care, initiatives to address this
      deficiency are a priority.

PMID- 15725640
TI  - Genetics and genetic testing: are GPs likely to attend training courses?
AB  - BACKGROUND: GPs must make difficult screening and diagnostic decisions regarding
      genetic testing for different cancers. Educational programs may improve knowledge
      and enable more appropriate referral. METHODS: A postal survey of all general
      practitioners (GPs) in Northern Ireland (N = 534; response rate = 49.4%) asked
      GPs if they would attend 3 different types of training courses in genetics.
      RESULTS: Almost 75% indicated that they would be likely and/or very likely to
      attend such courses. Women and GPs who had been qualified recently were most
      likely to attend (P < .005, P < .05). CONCLUSION: The results suggest that GPs
      are interested in training courses. Male GPs and GPs who have been qualified for
      longer should be specifically targeted.

PMID- 15725641
TI  - Gender differences in patients needs and concerns to diagnostic tests for
      possible cancer.
AB  - BACKGROUND: Little is known about the difference between the concerns of men and
      women prior to undergoing diagnostic tests for cancer. METHODS: A convenience
      sample of 129 outpatients completed a survey. RESULTS: No statistically
      significant differences were found between male and female patients; however,
      patients evaluated for gender-specific cancers reported a significantly (P < .01)
      higher mean score for concerns related to sexuality, reproductive ability, and
      intimate relationships. Almost half (46%) of the patients reported not receiving
      any or not enough information before the procedure. CONCLUSIONS: Men and women
      have similar concerns; however, there are significant differences in the concerns
      of patients undergoing a procedure for a gender-specific versus a non-gender
      specific cancer. Some patients reported inadequate procedural information,
      suggesting that improvements are needed in communication and health education
      efforts.

PMID- 15725642
TI  - Breast health information: messages that appeal to young women and older women of
      color.
AB  - BACKGROUND: In this study, we asked women directly for their information needs
      and format preferences related to breast cancer education. METHODS: Thirty focus
      groups were conducted nationwide with young women and women of color age 40 and
      older. RESULTS: Women wanted breast cancer messages to convince them that they
      are at risk and that screening is critical and to provide clear and detailed
      information about breast cancer and breast cancer screening guidelines. Women
      preferred to receive information from health care providers and media outlets.
      CONCLUSIONS: Women have a variety of suggestions related to breast cancer
      education that can be used in the development of educational interventions.

PMID- 15725643
TI  - Evaluation of a training program to prepare community health representatives to
      promote breast and cervix cancer screening among native american women.
AB  - BACKGROUND: Native American women have very poor 5-year breast and cervix cancer
      survival rates compared to other US population groups. We evaluated a training
      program that prepares community health representatives (CHRs) to promote
      prevention and early detection of these diseases. Two questions guided the
      evaluation: (1) Are CHRs an appropriate focus of training? and (2) Does training
      empower CHRs and, indirectly, their facilities to educate about breast and cervix
      cancer, promote screening, and teach breast self-exam skills to American Indian
      and Alaska Native women? METHODS: Twenty CHRs (3 Indian Health Service regions, 9
      separate employers) responded to a telephone survey consisting of Likert scale
      and multiple option and short-answer questions. Analysis relied on descriptive
      statistics and measures of central tendency. RESULTS: By tenure, cultural and
      community membership, and ability to adapt to audience needs and setting demands,
      CHRs make appropriate training recipients. Training improves skills and their use
      and appears to increase employers' reliance on CHRs for screening promotion and
      education about cancer. Posttraining, more women hear and heed the screening
      message. CONCLUSIONS: CHRs are an appropriate focus of training. Training leads
      to increased screening-related activities and should be continued and expanded.

PMID- 15725644
TI  - "Good health for new years": development of a cervical cancer control outreach
      program for Vietnamese immigrants.
AB  - BACKGROUND: Cervical cancer incidence rates are higher among Vietnamese American
      women than among any other race/ethnic group in the United States. High rates of
      cervical cancer are associated with low rates of Papanicolao (Pap) testing
      adherence. METHODS: Twenty-five qualitative interviews and 5 focus groups were
      conducted with Vietnamese women. RESULTS: Interviews and focus groups revealed
      unanticipated information about sociocultural influences on women's beliefs about
      risk factors for cervical cancer. These data were utilized to develop culturally
      appropriate outreach materials. CONCLUSIONS: Engaging with the target community
      enabled the development of culturally appropriate materials addressing cervical
      cancer risk factors and encouraging Pap testing adherence.

PMID- 15725645
TI  - A model of perceived risk for colorectal cancer among Japanese Americans.
AB  - BACKGROUND: Despite the higher rate of colorectal cancer (CRC) among Japanese
      Americans, little is known about their risk perceptions. The objective of this
      study was to test an exploratory model explaining psychosocial pathways to
      perceived risk of CRC. METHODS: The postulated model was tested using path
      analysis with data from a random sample of 306 Japanese Americans aged 30 and
      older. RESULTS: The model fit the data very well: chi(2)(10) = 10.22, P = .42;
      goodness-of-fit index = .993; comparative fit index = .999; and root mean square
      are of approximation = .008. Cancer fear exerted the strongest effect on
      perceived risk followed by family history. CONCLUSIONS: Risk communication for
      Japanese Americans should be tailored to individual emotional patterns associated
      with cancer to alleviate fear that may impede accurate risk self-assessment.

PMID- 15725647
TI  - Anticonvulsant hypersensitivity syndrome leading to reversible myocarditis.
AB  - A 67-year old Caucasian female was diagnosed with anticonvulsant hypersensitivity
      syndrome (AHS) after she developed the triad of high fevers, maculo-papular rash
      and internal organ involvement ten weeks after the institution of prophylactic
      phenytoin for resection of a meningioma. She developed congestive heart failure,
      with a substantial reduction in ejection fraction (EF) by an echocardiogram and
      serum cardiac enzyme elevation. In the setting of AHS, this was consistent with a
      drug-induced myocarditis. Treatment consisted of removal of the offending drug,
      diuretics and high dose steroids. Six weeks later her symptoms had completely
      resolved, with a return to a normal EF.

PMID- 15725648
TI  - The administration of retinoic acid down-regulates cAMP-responsive element
      modulator (CREM) mRNA in vitamin A-deficient testes.
AB  - Studies using genetics and vitamin A deficiency (VAD) have shown that vitamin A
      and retinoids play essential roles in spermatogenesis at the pre-meiotic stage.
      To understand the mechanisms of control in spermatogenesis by retinoic acid, we
      investigated whether retinoic acids regulate the expression of downstream
      transcription factors that are essential for spermatogenesis. In this study, we
      found that administration of all-trans retinoic acid (ATRA) or retinol to VAD
      rats down-regulates the testicular mRNA levels of the cAMP responsive element
      modulator (CREM), an essential transcription factor for spermatogenesis.
      Conversely, depletion of retinoids from the diet leds to an up-regulation of CREM
      expression in adult testes. In addition, RT-PCR analysis indicated that ATRA
      specifically represses the expression of the activator spliced variant of CREM
      (CREMtau). These results suggest that retinoids function as a negative regulator
      of CREM expression in testes.

PMID- 15725649
TI  - Effects of fermentation temperature on the content and composition of isoflavones
      and beta-glucosidase activity in sufu.
AB  - Sufu is a popular fermented tofu product in China. The low quality of sufu
      produced in the hot summer is a big problem in sufu manufacture, so we prepared
      sufu at two different temperatures, 26 degrees C as normal and 32 degrees C as
      high temperature, and the effects of temperature on isoflavones and beta
      glucosidase activity were investigated. Fermentation temperature did not cause
      significant differences in the recovery of isoflavones, but resulted in a
      different redistribution of isoflavone isomers in sufu. Sufu fermented at 26
      degrees C was richer in isoflavone aglycones than at 32 degrees C; the enrichment
      of isoflavone aglycones might have the advantage of enhancing the physiological
      function. No 6''-O-malonyl-glucosides were detected in sufu fermented at 26
      degrees C, whereas some 6''-O-malonyl-glucosides were found at 32 degrees C. A
      fermentation temperature of 26 degrees C benefited the beta-glucosidase
      production by fungi, which contributed to valid conversion from beta-glucosides
      to aglycones. It was also found that beta-glucosidase converted beta-glucosides
      more effectively than 6''-O-malonyl-glucosides and 6''-O-acetyl-glucosides into
      aglycones.

PMID- 15725650
TI  - The necessity of niacin in rats fed on a high protein diet.
AB  - It is known that niacin itself is not necessary in rats when tryptophan is given
      in adequate amounts, because rats can biosynthesize niacin from tryptophan. In
      our experiment, young rats were fed on a 20%, 40%, 60%, or 70% casein diet with
      or without niacin. The rats fed on the 20%, 40%, and 60% casein diets did not
      require niacin for growth, but the rats fed on the 70% casein diet needed it.
      This phenomenon was attributed to the supposition that liver aminocarboxymuconate
      semialdehyde decarboxylase activities increased according with the dietary casein
      levels. The conversion ratio of tryptophan-niacin in rats fed on the 70% casein
      diet became extremely low, and then the rats needed niacin.

PMID- 15725651
TI  - Structural and functional characterization of polyphenols isolated from acerola
      (Malpighia emarginata DC.) fruit.
AB  - Two anthocyanins, cyanidin-3-alpha-O-rhamnoside (C3R) and pelargonidin-3-alpha-O
      rhamnoside (P3R), and quercitrin (quercetin-3-alpha-O-rhamnoside), were isolated
      from acerola (Malpighia emarginata DC.) fruit. These polyphenols were evaluated
      based on the functional properties associated with diabetes mellitus or its
      complications, that is, on the radical scavenging activity and the inhibitory
      effect on both alpha-glucosidase and advanced glycation end product (AGE)
      formation. C3R and quercitrin revealed strong radical scavenging activity. While
      the inhibitory profiles of isolated polyphenols except quercitrin towards alpha
      glucosidase activity were low, all polyphenols strongly inhibited AGE formation.

PMID- 15725652
TI  - Three oxygenated cyclohexenone derivatives produced by an endophytic fungus.
AB  - Three cyclohexenone derivatives, (4S,5S,6S)-5,6-epoxy-4-hydroxy-3-methoxy-5
      methyl-cyclohex-2-en-1-one (1), (4R,5R)-4,5-dihydroxy-3-methoxy-5-methyl-cyclohex
      2-en-1-one (2), and (4R,5S,6R)-4,5,6-trihydroxy-3-methoxy-5-methyl-cyclohex-2-en
      1-one (3), were isolated from unpolished rice fermented with an xylariaceous
      endophytic fungus (strain YUA-026). The structures of three compounds were
      established on the basis of spectroscopic analyses and chemical conversion. The
      minimum inhibitory concentrations of 1 and 3 were 100 microg/ml and 400 microg/ml
      against Staphylococcus aureus, 100 microg/ml and 200 microg/ml against
      Pseudomonas aeruginosa, and 200 microg/ml and >400 microg/ml against Candida
      albicans, respectively. In addition, 1 and 3 exhibited phytotoxic activity
      against lettuce.

PMID- 15725653
TI  - Indole hydroxylation by bacterial cytochrome P450 BM-3 and modulation of activity
      by cumene hydroperoxide.
AB  - Cytochrome P450 BM-3 from Bacillus megaterium catalyzed NADPH-supported indole
      hydroxylation under alkaline conditions with homotropic cooperativity toward
      indole. The activity was also found with the support of H2O2, tert-butyl
      hydroperoxide (tBuOOH), or cumene hydroperoxide (CuOOH). Enhanced activity and
      heterotropic cooperativity were observed in CuOOH-supported hydroxylation, and
      both the Hill coefficient and substrate concentration required for half-maximal
      activity in the CuOOH-supported reaction were much lower than those in the H2O2-,
      tBuOOH-, or NADPH-supported reactions. CuOOH greatly enhanced NADPH consumption
      and indole hydroxylation in the NADPH-supported reaction. However, when CuOOH was
      replaced by tBuOOH or H2O2, heterotropic cooperativity was not observed. Spectral
      studies also confirmed that CuOOH stimulated indole binding to P450 BM-3.
      Interestingly, a mutant enzyme with enhanced indole-hydroxylation activity, F87V
      (Phe87 was replaced by Val), lost homotropic cooperativity towards indole and
      heterotropic cooperativity towards CuOOH, indicating that the active-site
      structure affects the cooperativities.

PMID- 15725654
TI  - Short-term feeding of fish oil down-regulates the expression of pyruvate
      dehydrogenase E1 alpha subunit mRNA in mouse brain.
AB  - Previous studies have suggested that docosahexaenoic acid (DHA), contained in
      fish oil, prevents brain disease. In the current study, the effect of fish oil
      feeding on gene expression in the brain was investigated by suppression
      subtractive hybridization. We found that pyruvate dehydrogenase E1 alpha
      (PDHE1alpha) mRNA expression is down-regulated by fish oil feeding. We examined
      whether the expression of PDHE1alpha mRNA is altered by DHA treatment in
      differentiated PC12 cells. PDHE1alpha mRNA was reduced by supplementation of DHA
      with a significant decrease in cellular ATP level. These results indicate that
      fish oil feeding might modulate energy metabolism in the brain.

PMID- 15725655
TI  - Nobiletin, a citrus flavonoid, down-regulates matrix metalloproteinase-7
      (matrilysin) expression in HT-29 human colorectal cancer cells.
AB  - Overexpression of matrix metalloproteinases (MMPs) is associated with cancer
      metastasis. We assessed mRNA expression of MMPs in six human colorectal cancer
      cell lines and found a considerable level of MMP-7 expression in HT-29 cells.
      Next, we searched for natural and synthetic compounds that cause a reduction in
      the production of proMMP-7 protein, and found that nobiletin (NOB), quercetin,
      valeryl salicylate, and sulindac sulfone demonstrated marked inhibition.
      Importantly, NOB attenuated proMMP-7 protein and its mRNA expression both
      concentration- and time-dependently via a reduction of activator protein-1 (AP-1)
      DNA binding activity, suggesting it as a promising agent for suppression of
      cancer cell invasion and metastasis through MMP-7 gene repression.

PMID- 15725656
TI  - Biosynthetic origin of the carbon skeleton and nitrogen atom of pamamycin-607, a
      nitrogen-containing polyketide.
AB  - The biosynthesis of pamamycin-607 (PM-607), a sixteen-membered macrodiolide
      compound, was studied with 13C- and 15N-labeled precursor units in Streptomyces
      alboniger. Feeding experiments with 13C-labeled acetate or propionate indicate
      that the carbon skeleton of PM-607 was derived from six acetate, four propionate
      and three succinate units. MS analyses of 15N-labeled PM-607 suggest that the
      nitrogen atom in PM-607 was derived from the alpha-amino group of an amino acid.

PMID- 15725657
TI  - Formation of trans-verbenol and verbenone from alpha-pinene catalysed by
      immobilised Picea abies cells.
AB  - Both enantiomers and the racemate of alpha-pinene were transformed by Picea abies
      cells immobilised on alginate. The main products were cis- and trans-verbenol,
      the later being further transformed to verbenone. The enantiomeric purity of each
      product more or less corresponded to that of the substrate. Transformation by
      free cells was faster than that by the immobilised cells. The ratio of products
      differed to some extent between the transformation by free and immobilised cells.

PMID- 15725658
TI  - Control of tomato bacterial wilt without disinfection using a new functional
      polymer that captures microbial cells alive on the surface and is highly
      biodegradable.
AB  - This report describes a green chemical method for controlling soil-borne plant
      diseases without disinfection using an equimolar copolymer of N-benzyl-4
      vinylpyridinium chloride with styrene (PBVP-co-ST) that captures microbial cells
      alive on the surface and is highly biodegradable. Tomato bacterial wilt caused by
      Ralstonia solanacearum was controlled by the addition of sawdust coated with PBVP
      co-ST prior to transplantation. This effected 87% reduction in appearance and 89%
      reduction in the index of symptom under appropriate conditions. The coated
      sawdust did not exhibit bactericidal activity. The half-life of PBVP-co-ST was
      5.6 d when treated with activated sludge in soil. The disease control was
      explained in terms of reduction of infectious contact between the roots of tomato
      and the cells of R. solanacearum due to coagulation-like interaction between
      microbial cells and the coated sawdust, in addition to capture of microbial cells
      by the coated sawdust.

PMID- 15725659
TI  - Distribution of gibberellins and expressional analysis of GA 20-oxidase genes of
      morning glory during fruit maturation.
AB  - Gibberellins A1/3 (GA1/3) and GA20 appeared earlier in surrounding tissues
      (pericarps/carpel/placenta) than in developing seeds of morning glory. The
      content of GA1/3 became higher in seeds than in the surrounding tissues at 9 days
      after anthesis (DAA), while that of GA20 stayed lower in seeds even at 12 DAA,
      suggesting the possibility that GA20 was translocated into seeds from the
      surrounding tissues and converted to GA1/3. The site of biosynthesis of GA20 in
      the fruits was determined by RNA-blotting and in situ hybridization of GA 20
      oxidase genes (InGA20ox1, InGA20ox2). InGA20ox1 was not expressed in the
      surrounding tissues but in seeds, while no signal due to InGA20ox2 was detected
      in neither tissue. The expression of InGA20ox1 started in the seed coat near the
      hilum and spread in the seed coat like those of GA 3-oxidase and GA-inducible
      alpha-amylase genes. These observations suggest that GA biosynthesis is tissue
      specifically and time-dependently regulated in the fruit of morning glory.

PMID- 15725660
TI  - On a salmon (Oncorhynchus [corrected] keta) liver RNase, belonging to RNase T2
      family: primary structure and some properties.
AB  - A base-nonspecific and acid ribonuclease (RNase Ok2) was purified from the liver
      of a salmon (Oncorhnchus keta) to a homogeneous state by SDS-PAGE. The primary
      structure of RNase Ok2 was determined by protein chemistry and molecular cloning.
      The RNase Ok2 was a glycoprotein and consisted of 216 amino acid residues. Its
      molecular mass of protein moiety was 25,198, and its amino acid sequence showed
      that it belongs to the RNase T2 family of enzymes. The optimal pH of RNase Ok2
      was around 5.5. The base preferences at the B1 and B2 sites were estimated from
      the rates of hydrolysis of 16 dinucleoside phosphates to be G>>A>U, C, and
      G>A>U>C respectively. In this enzyme, one of the three histidine residues which
      have been thought to be important for catalysis of RNase Rh, a typical RNase of
      this family of enzymes, His104 was replaced by tyrosine residue. Based on the
      results, the role of H104, which has been proposed to be a phosphate binding site
      with a substrate, was reconsidered, and we proposed a revised role of this His
      residue in the hydrolysis mechanism of RNase T2 family enzymes.

PMID- 15725661
TI  - Vaticanol C-induced cell death is associated with inhibition of pro-survival
      signaling in HL60 human leukemia cell line.
AB  - Recently, we found that vaticanol C (a resveratrol tetramer), which was isolated
      from stem bark of Dipterocarpaceae, exhibited growth suppression and induction of
      apoptosis via the loss of mitochondrial membrane potential and consequent
      caspases activation. The detailed mechanisms are not clearly understood. We
      decided to attempt to gain further insight into the mechanisms underlying
      vaticanol C-induced apoptosis in HL-60 cells. Treatment of HL-60 cells with
      vaticanol C was found to cause a marked decrease in the level of phosphorylated
      extracellular signal-regulated kinase (ERK) concurrent with inhibited
      phosphorylation of its upstream kinase mitogen-activates protein kinase kinase
      (MEK). Moreover, exposure to vaticanol C led to a significant reduction in the
      level of phosphorylated Akt. Thus, vaticanol C induced inhibition of both ERK and
      Akt phosphorylation, resulting in reduced phosphorylation of Bad. These results
      suggest that vaticanol C might induce apoptosis via a mechanism involving
      activation of Bad through disruption of pro-survival signaling pathways.

PMID- 15725662
TI  - beta-Hydroxyergothioneine, a new ergothioneine derivative from the mushroom
      Lyophyllum connatum, and its protective activity against carbon tetrachloride
      induced injury in primary culture hepatocytes.
AB  - A new ergothioneine derivative named beta-hydroxyergothioneine was isolated from
      the mushroom Lyophyllum connatum. Ergothioneine,N-hydroxy-N',N'-dimethylurea, and
      connatin (N-hydroxy-N',N'-dimethylcitrulline) were also isolated. All the
      compounds displayed the ability to scavenge free radicals, based on a 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Structural
      determination, including the absolute stereochemistry of beta
      hydroxyergothioneine, was achieved by spectroscopic analysis and X-ray
      crystallography. The radical scavenging activity of beta-hydroxyergothioneine was
      almost the same as that of ergothioneine. beta-Hydroxyergothioneine showed the
      greatest protective activity against carbon tetrachloride-induced injury in
      primary culture hepatocytes.

PMID- 15725664
TI  - Enantioselective total synthesis of enokipodins A-D, antimicrobial sesquiterpenes
      produced by the mushroom, Flammulina velutipes.
AB  - The first enantioselective total synthesis of enokipodins A, B, C and D, highly
      oxidized alpha-cuparenone-type sesquiterpenoids possessing antimicrobial
      activity, was accomplished in 8-28% overall yields from methyl (2,5-dimethoxy-4
      methylphenyl)acetate by applying Meyers' diastereoselective alkylation protocol
      for the construction of their C7-quaternary asymmetric center. The present
      synthesis confirmed the absolute configuration of the enokipodins, and also
      constitutes a formal enantioselective synthesis of (S)-1,4-cuparenediol and (S)
      cuparene-1,4-quinone.

PMID- 15725663
TI  - Gene cloning, overproduction, and characterization of thermolabile alkaline
      phosphatase from a psychrotrophic bacterium.
AB  - The gene encoding alkaline phosphatase from the psychrotrophic bacterium
      Shewanella sp. SIB1 was cloned, sequenced, and overexpressed in Escherichia coli.
      The recombinant protein was purified and its enzymatic properties were compared
      with those of E. coli alkaline phosphatase (APase), which shows an amino acid
      sequence identity of 37%. The optimum temperature of SIB1 APase was 50 degrees C,
      lower than that of E. coli APase by 30 degrees C. The specific activity of SIB1
      APase at 50 degrees C was 3.1 fold higher than that of E. coli APase at 80
      degrees C. SIB1 APase lost activity with a half-life of 3.9 min at 70 degrees C,
      whereas E. coli APase lost activity with a half-life of >6 h even at 80 degrees
      C. Thus SIB1 APase is well adapted to low temperatures. Comparison of the amino
      acid sequences of SIB1 and E. coli APases suggests that decreases in
      electrostatic interactions and number of disulfide bonds are responsible for the
      cold-adaptation of SIB1 APase.

PMID- 15725665
TI  - Molecular dissection of the promoter of the light-induced and circadian
      controlled APRR9 gene encoding a clock-associated component of Arabidopsis
      thaliana.
AB  - In the model higher plant Arabidopsis thaliana, a number of circadian clock
      associated protein components have recently been identified. Among them, a small
      family of ARABIDOPSIS PSEUDO-RESPONSE REGULATORS (APRR1/TOC1, APRR3, APRR5,
      APRR7, and APRR9) is interesting because the most probable clock component TIMING
      OF CAB EXPRESSION 1 (TOC1) belongs to this family. Several lines of evidence have
      already been accumulated to support the view that not only APRR1/TOC1 but also
      other APRR family members are crucial for a better understanding of the molecular
      link between circadian rhythm and light-signal transduction. Among the APRR1/TOC1
      family members, the circadian-controlled APRR9 gene is unique in that its
      expression is rapidly induced by light at the level of transcription. In this
      study we dissected the regulatory cis-elements of the light-induced and/or
      circadian-controlled APRR9 promoter by employing not only a mutant plant carrying
      a T-DNA insertion in the APRR9 promoter, but also a series of APRR9-promoter::LUC
      (luciferase) reporters that were introduced into an Arabidopsis cultured cell
      line (T87 cells). Taking the results of these approaches together, we provide
      several lines of evidence that the APRR9 promoter contains at least two
      distinctive and separable regulatory cis-elements: an "L element" responsible for
      the light-induced expression, followed by an "R element" necessary for the
      fundamental rhythmic expression of APRR9. Furthermore, APRR1/TOC1 was implicated
      in the L-element-mediated light response of APRR9, directly or indirectly.

PMID- 15725666
TI  - Synthesis and algicidal activity of (+)-cyanobacterin and its stereoisomer.
AB  - (+)-Cyanobacterin, a photosynthesis inhibitor of freshwater cyanobacterium
      Schytonema hofmanni, was synthesized in 6 steps from a readily accessible chiral
      synthon 5R-5-(l-menthyloxy)-2(5H)furanone.

PMID- 15725667
TI  - Microstructures of bread dough and the effects of shortening on frozen dough.
AB  - Three types of straight doughs different in combination of yeast and shortenings
      (RLS20, FTS20, and FTS80) were prepared, and the structure of the frozen doughs
      was examined under a microscope after staining protein or lipid droplets. Even
      after 2 months of frozen storage, distinct changes were not found in the gluten
      network of FTS80, although significant damages in the dough structures of FTS20
      and RLS20 appeared after only one month of frozen storage. These results suggest
      that the gluten networks loosen and decrease in the water retention ability, and
      it may be concluded that the lipid is removed from the gluten protein due to the
      decrease in water in the continuous protein phase. The resulting product from the
      damage to the gluten matrix gave rise to fusion of lipid droplets and an increase
      in their size. Because of the difference in fatty acid composition, the lipids of
      shortening S80 are presumed to interact more strongly with gluten proteins and to
      keep the gluten matrix from damage in comparison with the lipids of shortening
      S20.

PMID- 15725668
TI  - Sericin enhances attachment of cultured human skin fibroblasts.
AB  - Human skin fibroblasts were cultured on sericin prepared from cocoon shells. The
      living cell number after 72 h was enhanced to 250% of the no-sericin control. The
      increase was due to the acceleration of the initial attachment of the cells. It
      was found that sericin M, the main component of about 400 kDa, and its serine
      rich repetitive domain were the active principles.

PMID- 15725669
TI  - Cloning, expression in yeast, and functional characterization of CYP76A4, a novel
      cytochrome P450 of petunia that catalyzes (omega-1)-hydroxylation of lauric acid.
AB  - A cDNA clone of a novel cytochrome P450, CYP76A4, was isolated from Petunia
      hybrida. The cDNA clone contained an open reading frame (ORF) encoding a
      predicted 510 amino acid polypeptide. The CYP76A4 cDNA was expressed in yeast
      Saccharomyces cerevisiae AH22. Recombinant yeast microsomes containing the
      CYP76A4 hemoprotein were found to catalyze (omega-1)-hydroxylation of lauric
      acid.

PMID- 15725670
TI  - Circadian-associated rice pseudo response regulators (OsPRRs): insight into the
      control of flowering time.
AB  - A small family of plant proteins, designated PSEUDO RESPONSE REGULATORS (PRRs),
      is crucial for a better understanding of the molecular link between circadian
      rhythm and photoperiodic control of flowering time in the dicotyledonous model
      plant Arabidopsis thaliana. Recently, we showed that the monocotyledonous model
      plant Oryza sativa also has homologous members of the OsPRR family (Oryza sativa
      PRR). In the previous experiments with rice, we mainly characterized a japonica
      variety (Nipponbare). By employing an indica variety (Kasalath), in this study we
      further characterized OsPRRs with reference to the photoperiod sensitivity Hd
      (Heading date) QTL (quantitative trait loci) implicated in the control of
      flowering time in rice. The circadian-controlled and sequential expression
      profiles of the five OsPRR genes were observed not only for Nipponbare but also
      for Kasalath. Then each of these OsPRR genes was mapped on the rice chromosomes.
      Among these OsPRR genes, OsPRR37 was mapped very closely to Hd2-QTL, which was
      identified as the major locus that enhances the photoperiod sensitivity of
      flowering in Nipponbare. Furthermore, we found that Kasalath has a severe
      mutational lesion in the OsPRR37 coding sequence.

PMID- 15725671
TI  - Transient RNAi induction against endogenous genes in Arabidopsis protoplasts
      using in vitro-prepared double-stranded RNA.
AB  - RNA interference is a powerful technique for suppressing gene functions in many
      eukaryotes including plants. Here we show that introduction of double-stranded
      RNA into Arabidopsis protoplasts leads to marked silencing of endogenous genes,
      as observed previously for transgenes [Biosci. Biotechnol. Biochem., 67, 2674
      2677 (2003)]. This simple system should be useful for functional analysis of
      genes involved in fundamental cellular processes.

PMID- 15725672
TI  - Cold-active polygalacturonase from psychrophilic-basidiomycetous yeast
      Cystofilobasidium capitatum strain PPY-1.
AB  - We purified and characterized a cold-active polygalacturonase (PG) from the
      extracellular fraction of Cystofilobasidium capitatum strain PPY-1. The purified
      PG from strain PPY-1 has a molecular mass of about 44 kDa, and exhibited high
      activity at 0 degrees C, although its optimum temperature was 45 degrees C.
      Although the Km value for polygalacturonate as a substrate at 45 degrees C was
      found to be 11.2 mg/ml, it decreased gradually with decreasing temperature, and
      it was 0.66 mg/ml at 0 degrees C. Moreover, its cleavage pattern was of the endo
      type. These findings might indicate that PG from strain PPY-1 is a novel type of
      cold-active endo-PG that is able to degrade pectin compounds at low temperatures.

PMID- 15725673
TI  - Structural and functional analysis of pTB6 from Bifidobacterium longum.
AB  - The complete nucleotide sequence for pTB6 (3,624 bp) from Bifidobacterium longum
      was determined. This plasmid is 95% homologous in nucleotide (nuc) sequence, and
      also 92% in RepB aa sequence, to rolling circle replication (RCR) plasmids pKJ36
      and pB44, suggesting that pTB6 replicates by the rolling circle mechanism. The
      putative MembB, MobA, and protein encoding from orf (Orf) I detected were
      nonessential for plasmid replication. We constructed an immobile shuttle vector
      from pTB6 and pUC18, which transformed B. longum with a high efficiency of 2.5 x
      10(6) transformants/microg DNA.

PMID- 15725674
TI  - PRR5 (PSEUDO-RESPONSE REGULATOR 5) plays antagonistic roles to CCA1 (CIRCADIAN
      CLOCK-ASSOCIATED 1) in Arabidopsis thaliana.
AB  - In general, the clock (or oscillator) is central to circadian rhythms in many
      organisms. In the model higher plant Arabidopsis thaliana, the best candidates
      for clock components are CCA1 (CIRCADIAN CLOCK-ASSOCIATED 1) and LHY (LATE
      ELONGATED HYPOCOTYL), which are homologous Myb-related transcription factors. It
      is also believed that TOC1 (TIMING OF CAB EXPRESSION 1) is another component of
      the central oscillator. In this connection, we have been characterizing a small
      family of proteins, designated ARABIDOPSIS PSEUDO-RESPONSE REGULATOR (PRR1, PRR3,
      PRR5, PRR7, and PRR9), based on the fact that one of the members (PRR1) is
      identical to TOC1. Nevertheless, it is not yet certain whether other PRR family
      members are also implicated in clock function per se. To address this issue, in
      this study we examined a functional interaction between the CCA1 clock component
      and one of the PRR family members, PRR5, by employing transgenic lines
      overexpressing both the CCA1 and PRR5 genes. Evidence will be provided that PRR5
      plays an antagonistic role(s) to the putative CCA1 clock component.

PMID- 15725676
TI  - Culture system for embryos of blue-breasted quail from the blastoderm stage to
      hatching.
AB  - The blue-breasted quail (Coturnix chinensis), the smallest species in the order
      Galliforms, is a candidate model animal for avian developmental engineering
      because it is precocious and prolific. This species requires 17 days to hatch and
      8 to 9 weeks to mature to an adult body weight of about 50 g, whereas the
      Japanese quail (Coturnix japonica) requires 16 days to hatch and 6 to 8 weeks to
      mature to an adult body weight of 100 to 150 g. The early embryo is the most
      challenging embryonic stage in terms of culture and manipulation for avian
      biotechnology. We have evaluated various conditions for the culture of blue
      breasted quail embryos from the blastoderm stage to hatching. A hatchability rate
      of 26% (10/39) is among the best of the various culture conditions examined in
      the present study and the embryo culture system should facilitate advances in
      avian biotechnology.

PMID- 15725675
TI  - Effect of treadmill exercise on bone mass in female rats.
AB  - Increasing peak bone mass at skeletal maturity, minimizing bone loss during
      middle age and after menopause, and increasing bone mass and preventing falls in
      advanced age are important measures for preventing osteoporotic fractures in
      women. Exercise has generally been considered to have a positive influence on
      bone health. This paper reviews the effects of treadmill exercise on bone in
      young, adult, ovariectomized, and osteopenic female rats. Treadmill exercise
      increases cortical and cancellous bone mass of the tibia as a result of increased
      bone formation and decreased bone resorption in young and adult rats. The
      increase in lumbar bone mass seems to be more significant when long-term exercise
      is applied. Treadmill exercise prevents cancellous bone loss at the tibia as a
      result of suppressed bone resorption in ovariectomized rats, and increases bone
      mass of the tibia and mechanical strength of the femur, as a result of suppressed
      bone resorption and increased bone formation in osteopenic rats after
      ovariectomy. Treadmill exercise transiently decreases the serum calcium level as
      a result of accumulation of calcium in bone, resulting in an increase in serum
      1,25-dihydroxyvitamin D(3) level and a decrease in serum parathyroid hormone
      level. We conclude that treadmill exercise may be useful to increase bone mass in
      young and adult rats, prevent bone loss in ovariectomized rats, and increase bone
      mass and bone strength in osteopenic rats, especially in the long bones at weight
      bearing sites. Treadmill exercise may have a positive effect on the skeleton in
      young, and adult, ovariectomized, and osteopenic female rats.

PMID- 15725677
TI  - A novel model of obesity-related diabetes: introgression of the Lepr(fa) allele
      of the Zucker fatty rat into nonobese Spontaneously Diabetic Torii (SDT) rats.
AB  - An fa allele of the leptin receptor gene (Lepr(fa)) of the Zucker fatty rat was
      introduced into the genome of the Spontaneously Diabetic Torii (SDT) rat, an
      inbred model of nonobese type 2 diabetes mellitus, through the 'Speed congenic
      method'. The newly established congenic strain of a SDT rat for Lepr(fa) was
      maintained by intercrossing between fa-heterozygous littermates, and the
      phenotypes related to obesity and diabetes were investigated till 32 wks of age.
      SDT fa/fa rats of both sexes exhibited obesity, adiposity and insulin resistance
      associated with hyperphagia from the loss of leptin action. Interestingly, they
      developed diabetes from 5 wks of age in males and 8 wks in females with the
      incidences reaching 100% at 16 wks in males and 73% at 32 wks in females. In
      contrast, heterozygous (+/fa) and wild-type (+/+) rats developed spontaneous
      nonobese diabetes in males from approximately 20 wks, but not in females, as with
      the original SDT rats. These results indicate that the fa gene accelerates the
      onset of diabetes in SDT rats by making adiposity and/or insulin resistance as
      potent risk factors for development of their diabetes. The SDT.Lepr(fa) congenic
      rat strain is expected to be a novel model of obesity-related diabetes and could
      be a useful tool for studies of the genetic backgrounds of diabetes in response
      to fa-induced obesity.

PMID- 15725678
TI  - Ischemia-related changes in galanin expression in the dentate hilar region after
      transient forebrain ischemia in gerbils.
AB  - Although galanin (GAL) protects hippocampal neurons from ischemic damage, no
      study has examined ischemia-related changes in endogenous GAL in the hippocampal
      dentate gyrus. We investigated the chronological changes of GAL, well-known as
      the potassium channel opener, expression in the dentate gyrus at various times
      after 5 min of transient forebrain ischemia in gerbils. A few GAL-immunoreactive
      (IR) neurons were found in the polymorphic layer of the sham-operated group.
      Three hours after ischemia-reperfusion, the pattern of GAL immunoreactivity was
      similar to that of the sham-operated group and the number of GAL-IR neurons and
      immunoreactivity were highest 12 h after ischemic insult. At this time, GAL-IR
      neurons in the polymorphic layer showed strong GAL immunoreactivity. Thereafter,
      GAL-IR neurons and immunoreactivity significantly decreased in the dentate hilar
      region. Four days after ischemic insult, GAL-IR neurons were not detectable. In
      addition, the results of a Western blot study showed a pattern of GAL expression
      similar to the immunohistochemical changes. GAL protein content also was highest
      12 h after ischemia. In conclusion, the increased expression of endogenous GAL in
      the dentate gyrus after ischemia is related to response to the ischemic damage.

PMID- 15725679
TI  - Pattern of compensatory expression of voltage-dependent Ca2+ channel alpha1 and
      beta subunits in brain of N-type Ca2+ channel alpha1B subunit gene-deficient mice
      with a CBA/JN genetic background.
AB  - The Ca(2+) channel alpha(1B) subunit is a pore-forming component capable of
      generating N-type Ca(2+) channel activity. Although the N-type Ca(2+) channel
      plays a role in a variety of neuronal functions, alpha(1B)-deficient mice with a
      CBA/JN genetic background show no apparent behavioral or anatomical-histological
      abnormality, presumably owing to compensation by other Ca(2+) channels. In this
      study, we examined the mRNA expression of the alpha(1A), alpha(1C), alpha(1D),
      alpha(1E), beta(1), beta(2), beta(3) and beta(4) subunits in the olfactory bulb,
      cerebral cortex, hippocampus and cerebellum of alpha(1B)-deficient mice. We found
      that the mRNA expression levels of the alpha(1A), alpha(1C), alpha(1D),
      alpha(1E), beta(1), beta(2), beta(3) and beta(4) subunits were the same in the
      olfactory bulbs of wild, heterozygous and homozygous alpha(1B)-deficient mice. In
      the cerebral cortex, alpha(1A) mRNA in homozygous alpha(1B)-deficient mice was
      expressed at a higher level than in wild or heterozygous mice, but no difference
      in the expression levels of the alpha(1C), alpha(1D), alpha(1E), beta(1),
      beta(2), beta(3) and beta(4) subunits was found among wild, heterozygous and
      homozygous mice. In hippocampus and cerebellum, beta(4) mRNA in homozygous
      alpha(1B)-deficient mice was expressed at a higher level than in wild or
      heterozygous mice, but no difference in the expression levels of the alpha(1A),
      alpha(1C), alpha(1D), alpha(1E), beta(1), beta(2) and beta(3) subunits was found
      among wild, heterozygous and homozygous mice. These results suggest that the
      compensatory mechanisms differ in different brain regions of alpha(1B)-deficient
      mice with a CBA/JN genetic background.

PMID- 15725680
TI  - Biocompatibility and long-term toxicity of InnoPol implant, a biodegradable
      polymer scaffold.
AB  - InnoPol, a poly((D,L)-lactic-co-glycolic acid) [PLGA] 65/35 scaffold manufactured
      by special gas foaming methods in Korea, was subjected to tests to evaluate the
      degradation and tissue compatibility characteristics and long-term systemic
      toxicity in mice and rats. C57BL/6 mice and SD rats were implanted subcutaneously
      with 3-mm- and 1-mm-thick InnoPol circular discs, 10 mm in diameter,
      respectively, and sacrificed 8, 12, and 24 weeks after implantation. No test
      material-related effects were observed in mortality, clinical signs, body weight
      gain, food and water consumption, ophthalmologic signs, urinalysis, hematology,
      serum biochemistry parameters and organ weights of all animals implanted with
      InnoPol. Also, there were no systemic symptoms including metabolic alterations
      and inflammatory reactions in either mice or rats. In addition, no gross
      pathological findings, except skin lesions around the implantation sites, were
      found in the major organs. Although mild inflammation at the site of InnoPol
      implantation was confirmed from hematoxylin and eosin or Masson's trichrome
      staining at 8-12 weeks, the reactions had disappeared at 24 weeks following
      complete degradation of the scaffold, leaving granulomatous tissues that were
      similar to surgical wounds in sham operation controls without implants. These
      results suggest that InnoPol possesses good mechanical properties and tissue
      compatibility and does not cause any systemic toxicity other than transient local
      inflammatory reactions at the implantation site, and that it might be useful in
      applications as a medical device for implantation.

PMID- 15725681
TI  - SAMP1/Sku as a murine model for tubulointerstitial nephritis: a study using
      unilateral ureteral obstruction.
AB  - The SAMP1/Sku mouse is a substrain of the SAMP1 (senescence-accelerated-mouse
      prone 1) which exhibits renal mononuclear cell infiltration from a younger age.
      We hypothesized that this renal characteristic is related to the incidence of
      tubulointerstitial nephritis (TIN). The purpose of the present study was to
      evaluate the applicability of the SAMP1/Sku mouse as a murine model for TIN. TIN
      was experimentally induced by unilateral ureteral obstruction (UUO). The
      SAMP1/Sku and control ICR of both sexes received either a sham or UUO operation
      and were sacrificed 7 days after the operation. The kidneys of the mice were
      observed histopathologically, immunohistochemically and semiquantitatively. UUO
      kidneys showed mononuclear cell infiltration, tubular atrophy and interstitial
      fibrosis. In males, semiquantitative scores of mononuclear cell infiltration,
      tubular atrophy, and F4/80, alpha-smooth muscle actin (alpha-SMA) and
      transforming growth factor (TGF)-beta1 reactions were significantly higher in
      SAMP1/Sku than in ICR. Likewise, in females, tubular atrophy and F4/80 reaction
      scores were significantly higher in SAMP1/Sku than in ICR. In conclusion,
      induction of TIN damage by UUO was more serious in SAMP1/Sku mice than in ICR.
      Therefore, we propose that SAMP1/Sku mice, especially male SAMP1/Sku, have
      congenital risk factors for the development of TIN.

PMID- 15725682
TI  - Changes in autonomic control of heart associated with classical appetitive
      conditioning in rats.
AB  - The aim of this study was to examine the changes in autonomic control of the
      heart associated with classical appetitive conditioning in rats. We trained rats
      to learn that a movement into a test chamber was followed by delivery of reward
      (contextual conditioning) and performed power spectral analysis of heart rate
      variability from electrocardiograms recorded using the telemetry system. We
      investigated the sympathovagal balance of autonomic regulation of the heart in
      response to not only the conditioned stimulus (the movement into the test
      chamber), but also the unconditioned stimulus (reward), and compared the results
      of these two kinds of emotional states; it might be considered that "the reward
      expecting state" is evoked by the conditioned stimulus and "the reward-receiving
      state" is evoked by the unconditioned stimulus in rats. The reward-expecting
      state resulted in a significant increase in both low frequency (LF) power and
      high frequency (HF) power with no change in heart rate (HR) and LF/HF ratio,
      indicating that both sympathetic and parasympathetic activity increased with no
      change in sympathovagal balance. The reward-receiving state resulted in a
      significant increase in HR and a significant decrease in LF power, HF power, and
      LF/HF ratio, indicating that both sympathetic and parasympathetic activity
      decreased with predominance in the parasympathetic activity. These results
      suggest that the method performed in our present study might be useful for
      distinguishing between two different emotional states evoked by classical
      appetitive conditioning in rats.

PMID- 15725683
TI  - Diabetic complications in a new animal model (TSOD mouse) of spontaneous NIDDM
      with obesity.
AB  - The TSOD mouse has been established as an inbred strain with spontaneous
      development of diabetes mellitus as the first clinical signs of diabetes.
      Polydipsia and polyuria are observed at about 2 months old only in male mice,
      after which hyperglycemia and hyperinsulinemia are detected. Following these
      symptoms obesity gradually develops until about 12 months old. In
      histopathological examination of the pancreas, severe hypertrophy of pancreatic
      islets was observed due to proliferation and swelling of B cells. In the kidney,
      thickening of the basement membrane in glomeruli and an increase of the mesangial
      area were observed at 18 months old. Motor neuropathy in TSOD mice began to
      appear at 14 months old and most male mice at 17 months old showed weakness of
      front and hind paws caused by neuron degeneration in the peripheral nerve. In
      sensory neuropathy, the threshold in the tail pressure test decreased
      significantly at 12 months old. Light microscopic and electron microscopic
      examination of sciatic nerves showed a decrease in the density of nerve fibers by
      the endoneural fibrosis and loss of these fibers. Degenerative changes of
      myelinated fibers, separation of myelin sheaths with intralamellar edema and
      remyelination were frequently observed. In the severely affected nerve fibers,
      the lamellar structure was completely destroyed and macrophages migrated around
      the myelin sheath or invaded the intramyelin space. Considering these findings
      similar to non-insulin dependent diabetes mellitus (NIDDM) in humans, the TSOD
      mouse should be a useful model for the pathogenic study of diabetic
      complications, especially of peripheral neuropathy.

PMID- 15725684
TI  - Health surveillance of specific pathogen-free and conventionally-housed mice and
      rats in Korea.
AB  - The present study contains information about proper microbiological monitoring of
      laboratory animals' health and the standardization of microbiological monitoring
      methods in Korea. Microbiological quality control for laboratory animals,
      composed of biosecurity and health surveillance, is essential to guard against
      research complications and public health dangers that have been associated with
      adventitious infections. In this study, one hundred and twenty-two mice and
      ninety rats from laboratory animal breeding companies and one animal facility of
      the national universities in Korea were monitored in 2000-2003.
      Histopathologically, thickening of the alveolar walls and lymphocytic
      infiltration around the bronchioles were observed in mice and rats from
      microbiologically contaminated facilities. Cryptosporidial oocysts were observed
      in the gastric pits of only conventionally-housed mice and rats. Helicobacter
      spp. infection was also detected in 1 of 24 feces DNA samples in mice and 9 of 40
      feces DNA samples in rats by PCR in 2003, but they were not Helicobacter
      hepaticus. This paper describes bacteriological, parasitological, and virological
      examinations of the animals.

PMID- 15725685
TI  - Delayed persistent estrus induced by continuous lighting after inadequate
      acclimation in rats.
AB  - While the normal estrous cycle of adequately acclimated female rats was replaced
      by a persistent estrus (PE) under continuous lighting, the onset of PE was
      delayed following several irregular cycles without acclimation or after
      acclimation for one week, suggesting that transportation induces a significant
      critical stress.

PMID- 15725686
TI  - Optimum dose of LH-RH analogue Fertirelin Acetate for the induction of
      superovulation in mice.
AB  - The optimum dose for establishing superovulation in mice of Fertirelin Acetate
      (FA), an LH-RH analogue, was examined. Mice were subcutaneously injected with 5
      IU of hCG at 17:00 (Day 0), and with various doses of FA (0.001 to 1.0 microg)
      five times at 4 h intervals on and after 22:00 on Day 0. To induce ovulation, 5
      IU of hCG was again injected subcutaneously at 17:00 on Day 2. In the groups
      administered with doses ranging from 0.01 to 0.5 microg of FA, the number of
      ovulated eggs was significantly (p<0.05) larger than in the control group (12.9
      +/- 5.9). The greatest number of ovulated eggs (22.6 +/- 7.3) was obtained in the
      group administered with 0.025 microg of FA. The results indicate that the
      effective dose of LH-RH analogue, FA, is between 0.1 and 0.5 microg for
      superovulation induction in mice.

PMID- 15725687
TI  - Malignant NK/T-cell lymphoma associated with simian Epstein-Barr virus infection
      in a Japanese macaque (Macaca fuscata).
AB  - A case of spontaneous malignant lymphoma in a Japanese macaque (Macaca fuscata)
      was pathologically, etiologically and virologically studied. Nasal cavity was
      involved in the neoplastic lesions in addition to lymphoid and visceral tissues.
      Histopathological analyses revealed the presence of neoplastic cells classified
      into histiocytic Hodgkin-like cells and Reed-Sternberg-like cells. Histiocytic
      Hodgkin-like cells were CD16+ and CD20+, and the CD16+ cells were also positive
      for simian Epstein-Barr virus (sEBV)-encoded early RNA transcripts. RS-like cells
      were negative for CD3, CD16 and CD20. Antibodies to early antigen of sEBV were
      detected, while antibodies to simian T-cell leukemia virus-1 were negative. The
      case may correspond to EBV-associated nasal type NK/T-cell lymphoma in humans
      rather than Hodgkin lymphoma.

PMID- 15725688
TI  - Electron microscopic study of subcapsular cell hyperplasia in the adrenal glands
      of IQI/Jic mice.
AB  - Hyperplastic cells in subcapsular cell hyperplasia (SCH) lesion in adrenal glands
      of female IQI/Jic mice were examined by electron microscopy. These cells were
      small and polygonal, and had irregular nuclei, elongated mitochondria with
      lamellar cristae and dense lipid droplets. While these cells showed different
      features, some of them had desmosomes and basement membranes, and a few round
      mitochondria with tubular cristae as endocrine cells. These findings suggest that
      hyperplastic cells in SCH lesions might originate from endocrine blastemic cells.

PMID- 15725689
TI  - Role of thrombogenic factors in the development of atherosclerosis.
AB  - Hemostatic factors play a crucial role in generating thrombotic plugs at sites of
      vascular damage (atherothrombosis). However, whether hemostatic factors
      contribute directly or indirectly to the pathogenesis of atherosclerosis remains
      uncertain. Autopsy studies have revealed that intimal thickening represents the
      first stage of atherosclerosis and that lipid-rich plaque arises from such
      lesions. Several factors contribute to the start of intimal thickening. Platelets
      release several growth factors and bioactive agents that play a central role in
      development of not only thrombus but also of intimal thickening. We have been
      investigating which coagulation factors simultaneously, or subsequently with
      platelet aggregation, participate in thrombus formation. Tissue factor (TF) is an
      essential initiator of blood coagulation that is expressed in various stages of
      atherosclerotic lesions in humans and other animals. Factors including thrombin
      and fibrin, which are downstream of the coagulation cascade activated by TF, also
      contribute to atherosclerosis. TF is involved in cell migration, embryogenesis
      and angiogenesis. Thus TF, in addition to factors downstream of the coagulation
      cascade and the protease-activated receptor 2 activation system, would be a
      multifactorial regulator of atherogenesis.

PMID- 15725690
TI  - Relationship between insulin resistance and effect of atorvastatin in non
      diabetic subjects.
AB  - BACKGROUND: Although insulin resistance (IR) is present in non-diabetic subjects,
      it is unknown whether IR affects statin treatment. We assessed the relationship
      between IR and the changes of lipid profile in patients with hyperlipidemia
      treated by atorvastatin. METHODS: Forty-four non-diabetic patients were included.
      Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. We
      used the value of 2.5 as the threshold for IR. RESULTS: High-density lipoprotein
      (HDL) cholesterol at baseline was lower and triglyceride (TG) at baseline was
      higher in the IR group than in the nonIR group (p < 0.05). Changes in all lipid
      measurements did not differ between the two groups. HOMA-IR was correlated with
      HDL cholesterol at baseline and at follow-up and correlated with TG at baseline
      and at follow-up (r = -0.40, r = -0.53, r = 0.38, r = 0.35, p < 0.01,
      respectively). However, HOMA-IR did not associate with changes in total
      cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, and TG.
      CONCLUSION: The IR did not affect the degree of reduction in cholesterol by
      atorvastatin in non-diabetic subjects. The IR may influence hypertriglyceridemia
      greater than the effect of atorvastatin in non-diabetic subjects.

PMID- 15725691
TI  - Hyper-homocysteinemia is not a main feature of juvenile uncomplicated type 1
      diabetes.
AB  - Total plasma homocysteine (tHcy) was measured by high pressure liquid
      chromatography (HPLC) method in 28 patients (12 females and 16 males) at the
      onset of type 1 diabetes mellitus (T1DM), 4 females during diabetes ketoacidosis
      (DKA) and 154 (68 females and 86 males) during follow-up. Serum folate, pyridoxal
      5' phosphate (PLP) and Vitamin B12 (Vit B12) were also measured. Plasma tHcy
      levels were not found significantly different in T1DM patients known to have
      diabetes (males 9.2 +/- 7.7 and females 7.0 +/- 2.8 micromol/l) and in those who
      were newly diagnosed (males 9.7 +/- 4.8 and females 7.16 +/- 2.8 micromol/l) than
      in healthy controls (males 8.7 +/- 3.5 and females 7.8 +/- 2.55 micromol/l). Only
      a significant difference for sex was observed in known diabetes (p = 0.0281).
      Serum folate, PLP and Vit B12 were normal (12.6 +/- 3.6 ng/ml, 20.11 +/- 0.8
      ng/ml and 416.7 +/- 41.9 pg/ml) in all T1DM patients. Age significantly
      correlated with plasma tHcy. Only in 4 patients, studied during DKA, plasma tHcy
      was significantly lower (2.76 +/- 1.33 micromol/l, p < 0.001) than the healthy
      controls.

PMID- 15725692
TI  - Suppressive effect of cocoa powder on atherosclerosis in Kurosawa and Kusanagi
      hypercholesterolemic rabbits.
AB  - We investigated the suppressive effect of cocoa powder (cacao polyphenol content:
      7.8%) on atherosclerosis in a spontaneous familial hypercholesterolemic model,
      Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Six-month dietary
      administration of cocoa powder had no effects on body weight, hematology or blood
      chemistry parameters or a lipid profile in KHC rabbits. Antioxidative activity of
      low-density lipoprotein (LDL) was observed in the 2nd month and 3rd month of
      administration. Thiobarbituric acid reactive substances (TBARS), the marker of
      lipid peroxidation, in plasma were decreased in the cocoa powder treated group
      from the 2nd month of administration during the study period compared to that in
      the control group. The area of atherosclerotic lesions in th aorta was
      significantly smaller in the cocoa powder group (30.87%) than in the control
      (52.39%). Tissue cholesterol content also tended to decrease. Distensibility of
      the aortic wall was improved significantly in the cocoa powder treated group due
      to decreases in fatty streaks and intimal thickening compared to that in the
      control group. These results suggest that cocoa powder has suppressive effect on
      development of atherosclerotic lesions. We consider that antioxidative activity
      of polyphenols rich in cocoa powder may be a key factor for the anti
      atherosclerotic effect.

PMID- 15725693
TI  - Factor analysis of lifestyle-related factors in 12,525 urban Japanese subjects.
AB  - This study describes the clustering patterns of several lifestyle-related factors
      in urban Japanese subjects. The effect of aging on these patterns was also
      investigated. Data of 8 factors that included body mass index (BMI), blood
      pressure (BP), fasting plasma glucose (FPG), serum total cholesterol (TC),
      triglycerides (TG), high-density lipoprotein cholesterol (HDLc), gamma-glutamyl
      transferase (GGT), and cigarette smoking were analyzed for 12,525 individuals
      (4,591 men and 7,934 women) aged either 40, 50, or 60 years. Factor analysis
      showed eight factors clustered into 3 unrelated groups. BMI and BP were excluded
      in subjects aged 60 years. Our data showed that the effect of obesity on the
      prevalence of type 2 diabetes mellitus was age dependent. In spite of the
      established inverse relationship between TG and HDLc, we found that TG had an
      association with GGT. These results indicated that aging may have a major
      influence on the expression of multiple risk factors. The influence of BMI on the
      lifestyle-related factors appeared to be mostly expressed in younger people,
      while these factors appeared to be independent of BMI at age 60.

PMID- 15725694
TI  - Cutoff point separating affected and unaffected familial hypercholesterolemic
      patients validated by LDL-receptor gene mutants.
AB  - Familial hypercholesterolemia (FH) results from low-density lipoprotein (LDL)
      receptor gene mutations. Heterozygotes have twice normal LDL-cholesterol
      concentrations in early childhood, and experience early myocardial infarction. We
      demonstrated bimodal cholesterol frequency distributions, independently
      confirming existence of an identifiable hypercholesterolemic subpopulation. We
      assayed blood lipids in 181 FH patients genetically diagnosed and 100 unaffected
      relatives. Receiver operating characteristics curves were constructed. Total
      cholesterol and LDL-cholesterol concentrations showed bimodality. A total
      cholesterol cutoff of 225 mg/dl produced results agreeing with DNA testing
      (specificity, 98.5%; sensitivity, 99.4%). An LDL-cholesterol cutoff of 161-163
      mg/dl produced 98.5% specificity and 98.3% sensitivity. Areas under curves were
      0.9826 +/- 0.0058 for total cholesterol, and 0.9852 +/- 0.0043 for LDL
      cholesterol. In conclusion, we define total cholesterol and LDL-cholesterol
      levels of 225 and 160 mg/dl, respectively, as cutoff points of normal subjects
      and FH patients.

PMID- 15725695
TI  - A comparative crossover study of the effects of fluvastatin and pravastatin (FP
      COS) on circulating autoantibodies to oxidized LDL in patients with
      hypercholesterolemia.
AB  - This study compared the effects of fluvastatin and pravastatin on the in vivo
      oxidation of LDL in a crossover design to evaluate whether or not it is justified
      to switch between the two statins with regard to serum levels of lipids,
      lipoproteins, and apolipoproteins (apo), and circulating autoantibodies to
      oxidized LDL (OxLDL-Ab). Patients with hypercholesterolemia (n = 46) were
      randomly assigned into groups who received fluvastatin (20 mg/d) or pravastatin
      (10 mg/d). After 3 months, they were crossed to receive the other statin for
      another 3 months. Circulating levels of OxLDL-Ab were measured by an OxLDL IgG
      ELISA test. Fluvastatin and pravastatin similarly decreased serum levels of total
      cholesterol (TC), LDL-C, and apo B, and increased HDL(2)-C levels. After
      crossover to the other statin, these lipid parameters were not further changed by
      either statin. Before crossover, circulating levels of OxLDL-Ab were decreased in
      patients with fluvastatin treatment, but not in those with pravastatin treatment.
      After switching from the other statin, both fluvastatin and pravastatin further
      decreased OxLDL-Ab levels. In conclusion, fluvastatin at 20 mg/d and pravastatin
      at 10 mg/d are similar with regard to their efficacy in decreasing TC, LDL-C, and
      apo B levels and increasing HDL(2)-C levels. Fluvastatin lowered circulating
      levels of OxLDL-Ab, and these effects continued after switching to pravastatin.

PMID- 15725696
TI  - Risk evaluation of coronary heart disease and cerebrovascular disease by the
      Japan Atherosclerosis Society Guidelines 2002 using the cohort of the Holicos-PAT
      study.
AB  - Our purpose in this study was to evaluate the new JAS guidelines as a risk
      assessment tool in Japanese patients with hypercholesterolemia, using the cohort
      of the Holicos-PAT study. The Holicos-PAT study was designed as a prospective
      observational study. 2039 patients were followed with or without pravastatin for
      5 years. We assessed coronary heart disease (CHD) and cerebrovascular disease
      (CVD) risks by the patient categories described in the JAS guidelines. In the
      Holicos-PAT study, the primary endpoints were CHD, and the secondary endpoints
      were CVD and total mortality. CHD event includes onset and worsening of angina
      pectoris, performing CABG or PTCA, non-fatal and fatal myocardial infarction, and
      death from CHD including heart death and sudden death. CVD events are onset or
      recurrence of cerebral infarction, onset of cerebral hemorrhage, and death from
      cerebral infarction or hemorrhage. The event rates were calculated by the person
      years method, and the differences in event rates between category groups were
      analyzed by chi-square test. The event rates of CHD in Category A, B1, B2, B3, B4
      and C, were 1.1, 4.0, 2.8, 5.7, 18.2 and 38.8 per 1,000 person-years. The rates
      of CHD events in the higher risk category groups, Category B4 group (p = 0.004 in
      whole patients) and C group (p < 0.001 in whole patients), were significantly
      higher than that in the combined category groups A + B1 + B2. The event rates of
      CVD in Category A, B1, B2, B3, B4 and C, were 2.1, 1.8, 1.8, 0.6, 10.8 and 6.4
      per 1,000 person-years. The event rates of CHD in men were significantly higher
      than those in women, in categories B4 (p < 0.001) and C (p < 0.001). From these
      results, each category classified by accumulation of risk factors, showed
      increasing event rates of CHD and CVD. The categories in the JAS guidelines are
      useful to assess CHD and CVD risk in Japanese patients with hypercholesterolemia.
      However, the risk evaluation by the JAS guideline categories may underestimate
      the risk in men and overestimate it in women.

PMID- 15725698
TI  - Pathophysiological role of 20-HETE a cytochrome P450 metabolite of arachidonic
      acid.

PMID- 15725697
TI  - Characterization of the expression of TLR2 (toll-like receptor 2) and TLR4 on
      circulating monocytes in coronary artery disease.
AB  - TLRs are receptors involved in the recognition of pathogens by the innate immune
      system, and TLR2 and TLR4 play important roles in the activation of monocytes. A
      total of 105 consecutive patients who underwent coronary angiography comprised of
      46 with stable effort angina (SA), 41 with unstable angina (UA), and 18 with no
      significant CAD (CNT) were enrolled. The baseline expression levels of TLR2 and
      TLR4 on monocytes in peripheral blood mononuclear cells (PBMCs) were determined
      by flow-cytometric analysis. Since TLR2 expression has been reported to be
      regulated by TLR4 signaling, we cultured PBMCs with or without lipopolysaccharide
      (LPS, 1 microg/ml). At baseline, TLR4 levels (mean of fluorescence intensity ) in
      SA (145 +/- 58, p < 0.05) and UA (164 +/- 65, p < 0.01) were higher than those in
      CNT (107 +/- 37). As for TLR2, levels were higher in UA (108 +/- 36, p < 0.05)
      than in SA (94 +/- 18) and CNT (87 +/- 22). After stimulation with LPS, TLR2
      levels increased in SA but decreased in UA. In conclusions, TLR4 levels increased
      in both SA and UA. Monocytes in UA were characterized by elevated TLR2 levels and
      unresponsiveness of the TLR2 levels to TLR4 stimulation.

PMID- 15725699
TI  - Nuclear receptors as targets for drug development: peroxisome proliferator
      activated receptor gamma in mast cells: its roles in proliferation and
      differentiation.
AB  - Mast cells are derived from stem cells in bone marrow and their proliferation and
      differentiation are regulated by stimulation of stem cell factor derived from
      fibroblasts and/or IL-3 from T lymphocytes. The peroxisome proliferator-activated
      receptors (PPARs) are members of the nuclear hormone receptor superfamily and
      ligand-activated transcription factors. It has been reported that PPARgamma is
      expressed in mast cells, but its roles remain uncertain. Since mast cells produce
      and release prostaglandin D(2), which is metabolized to 15-deoxy-Delta(12,14)
      prostaglandin J(2), a candidate for the endogenous PPARgamma agonist, mast cells
      play roles in inflammation and immunological response via the PPARgamma pathway.
      We will mainly discuss the contribution of PPARgamma to the proliferation and
      functions in murine cultured bone marrow derived mast cells.

PMID- 15725700
TI  - Nuclear receptors as targets for drug development: crosstalk between peroxisome
      proliferator-activated receptor gamma and cytokines in bone marrow-derived
      mesenchymal stem cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      dependent nuclear receptor and regulates adipogenesis and fat metabolism.
      PPARgamma is activated by fatty acid derivatives and some synthetic compounds
      such as the thiazolidinediones. In addition, certain cytokines were known to
      affect the transactivation function of PPARgamma. However, the molecular
      mechanism of the functional interaction between PPARgamma and cytokine signaling
      remains unclear. We found that combined treatment of PPARgamma and cytokines (IL
      1 or TNF-alpha) inhibited adipogenesis and induced osteoblastgenesis in bone
      marrow-derived mesenchymal stem cells. Furthermore, we showed that the ligand
      dependent transactivation function of PPARgamma was suppressed by IL-1 and TNF
      alpha. This suppression was mediated through NF-kappaB activated by the TAK1/TAB1
      NIK cascade, a downstream cascade triggered with IL-1 or TNF-alpha signaling.
      Thus, we have identified a molecular mechanism of functional cross-talk between
      PPARgamma and cytokine signaling that may provide a theoretical basis for
      development of novel therapeutical strategies and design of novel compounds for
      treatment of obesity, diabetes, and some other chronic diseases.

PMID- 15725701
TI  - Nuclear receptors as targets for drug development: regulation of cholesterol and
      bile acid metabolism by nuclear receptors.
AB  - Nuclear receptors are ligand-dependent transcription factors that recently have
      been shown to play important roles in the metabolism of cholesterol and bile
      acids. Cholesterol homeostasis is maintained by de novo synthesis, absorption
      from diet, catabolism to bile acids and other steroids, and excretion into bile.
      Dysregulation of this mechanism leads to atherosclerosis and its life-threatening
      coronary and cerebrovascular sequelae. Conversion of cholesterol to bile acids in
      the liver is positively regulated by liver X receptor (LXR) alpha, a nuclear
      receptor for oxysterols. LXRalpha and LXRbeta, a second oxysterol receptor,
      regulate intestinal absorption and biliary excretion of cholesterol by inducing
      target gene expression. LXRs stimulate reverse cholesterol transport from
      peripheral tissues and exhibit antiatherogenic activity. Farnesoid X receptor
      (FXR), a bile acid receptor, represses bile acid synthesis and import in
      hepatocytes, stimulates bile acid export from cells, and protects hepatocytes
      from bile acid toxicity. Pregnane X receptor (PXR) and vitamin D receptor (VDR)
      respond to secondary bile acids and induce their catabolism. Thus, nuclear
      receptors play important roles in regulation of cholesterol and bile acid
      metabolism.

PMID- 15725702
TI  - Nuclear receptors as targets for drug development: the role of nuclear receptors
      during neural stem cell proliferation and differentiation.
AB  - The fate of stem cells, such as neural stem cells and hematopoietic stem cells,
      depends on strictly regulated signaling events including activation of nuclear
      receptors, resulting in subsequent gene induction. Recently, we demonstrated that
      PPARgamma, a ligand-activated nuclear receptor, plays an important role in
      regulating the proliferation and differentiation of murine neural stem cell
      (NSC). NSC prepared from heterozygous PPARgamma-deficient mouse exhibited a
      slower growth rate compared with that of wild-type mouse, which was also
      demonstrated in PPARgamma-knockdown NSC that was generated by the lentiviral
      vector-mediated RNA interference approach. These studies have important
      implications for understanding central nervous system functions and developing a
      therapy for neurodegenerative disorders. In this review, recent findings on stem
      cell biology, especially focusing on nuclear receptors in NSCs, including our
      current study, will be discussed.

PMID- 15725703
TI  - Nuclear receptors as targets for drug development: molecular mechanisms for
      regulation of obesity and insulin resistance by peroxisome proliferator-activated
      receptor gamma, CREB-binding protein, and adiponectin.
AB  - Obesity is defined as increased mass of adipose tissue, conferring a higher risk
      of cardiovascular and metabolic disorders such as diabetes, hyperlipidemia, and
      coronary heart disease. To investigate the role of transcriptional factors, which
      are involved in adipocytes differentiation and adiposity, we have generated
      peroxisome proliferator-activated receptor (PPAR) gamma or CREB-binding protein
      (CBP)-deficient mice by gene targeting. Heterozygous PPARgamma-deficient mice
      were protected from the development of insulin resistance due to adipocyte
      hypertrophy under a high-fat diet. Heterozygous CBP-deficient mice showed
      increased insulin sensitivity and were completely protected from body weight gain
      induced by a high-fat diet. PPARgamma or CBP deficiency results in increased
      effects of hormones such as adiponectin and leptin. Adiponectin was decreased in
      obesity and lipoatrophy, and replenishment of adiponectin ameliorated insulin
      resistance. Moreover, adiponectin-deficient mice showed insulin resistance and
      atherogenic phenotype. Finally, cDNA encoding adiponectin receptors (AdipoR1/R2)
      have been identified by expression cloning. The expression of AdipoR1/R2 appears
      to be inversely regulated by insulin in physiological and pathophysiological
      states such as fasting/refeeding, insulin deficiency, and hyperinsulinemia
      models, and it is correlated with adiponectin sensitivity. These results
      facilitate the understanding of molecular mechanisms of adiponectin actions and
      obesity-linked diseases such as diabetes and atherosclerosis and propose the
      molecular targets for anti-diabetic and anti-atherogenic drugs.

PMID- 15725705
TI  - Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular
      smooth muscle.
AB  - The Ca2+-dependent, reversible phosphorylation of the 20 kDa regulatory myosin
      light chain (MLC) plays a primary role in regulating the contraction of smooth
      muscle. However, it is well known that the Ca2+ signal is not the only factor
      which regulates such contraction, however, the alteration of the Ca2+ sensitivity
      in the contractile apparatus is also known to play an important role. The degree
      of MLC phosphorylation is determined by the balance of the activity between
      phosphorylation and dephosphorylation. Either the Ca2+-independent activation of
      MLC phosphorylation or the inhibition of MLC dephosphorylation causes a greater
      MLC phosphorylation for a given level of Ca2+ signal and thereby potentiates the
      myofilament Ca2+ sensitivity. The smooth muscle myosin light chain phosphatase
      (MLCP) consisting of three subunits was first isolated and cloned in the early
      '90s. The intensive investigation thereafter has uncovered the biochemical basis
      for regulating the activity of MLCP. The regulation of the MLCP activity is now
      considered to play a critical role in regulating the myofilament Ca2+
      sensitivity. There are three major mechanisms in the regulation of MLCP; (1) the
      phosphorylation of a 110 kDa regulatory subunit of MLCP (2) the conformational
      change of the trimeric structure, and (3) the inhibition by a smooth muscle
      specific inhibitor protein, CPI-17. Furthermore, some kinases have been found to
      phosphorylate the MLC and activate the contraction of smooth muscle in a Ca2+
      independent manner. Numerous protein kinases have been found to be involved in
      the regulation of MLC phosphorylation, and rho-kinase is one of the most
      frequently investigated kinases. The smooth muscle physiology is now asked to
      integrate the current understanding of the biochemical mechanisms and to clarify
      which kinases and/or proteins in the contractile apparatus play a physiological
      role in regulating the myofilament Ca2+ sensitivity and how such extracellular
      contractile stimulation modulates these mechanisms.

PMID- 15725706
TI  - Muscarinic receptor subtypes of the bladder and gastrointestinal tract.
AB  - The parasympathetic nervous system is responsible for maintaining normal
      intestinal and bladder function, contracting the smooth muscle by releasing the
      neurotransmitters acetylcholine (ACh) and ATP and relaxing sphincters by
      releasing nitric oxide. ACh is the main transmitter released and smooth muscle
      contraction is mediated via a mixed M2/M3 receptor population; M3 receptors
      acting via phospholipase C and M2 receptors acting via inhibition of adenylate
      cyclase. In ileal, colonic, gastric and bladder (detrusor) smooth muscle the
      density of M2 receptors is far greater than the density of M3 receptors, the
      M2:M3 ratio being 3:1 in most species including man. Despite the predominance of
      M2-receptors, direct contraction of intestinal and detrusor smooth muscle is
      mediated via the M3-receptor subtype and only this subtype is involved in
      contraction in vitro. Furthermore, knocking out the M3-receptor gene can have
      severe consequences on intestinal and bladder responses. In some tissues however
      M2-receptors may mediate an indirect "re-contraction" whereby a reduction in
      adenylate cyclase activity reverses the relaxation induced by beta-adrenoceptor
      stimulation. Thus, intestinal and bladder responses to muscarinic agonists are
      slightly depressed in M2 receptor knockout mice. The role of receptor subtypes in
      disease is unclear, but an enhancement of M2 receptor mediated responses has been
      reported to occur in diabetes. Animal models suggest that M2 receptors may play a
      greater role in some situations such as in the denervated bladder and intestine.
      In human disease the mechanisms operating are not so clear. Detrusor sensitivity
      to muscarinic agonists is enhanced in the neurogenic overactive bladder, but
      there is controversy surrounding the role of M2 receptors and conflicting results
      have been reported. Thus, the main muscarinic receptor mediating contraction in
      normal smooth muscle is the M3 receptor, but M2 receptors are also present and
      possibly may have an enhanced role in disease.

PMID- 15725707
TI  - Phenylephrine-induced vasoconstriction of the rat superior mesenteric artery is
      decreased after repeated swimming.
AB  - This study was performed to determine the effect of forced swimming on the
      vascular responsiveness of the rat superior mesenteric artery to phenylephrine,
      focusing on the involvement of locally produced substances. Repeated but not
      single sessions of forced swimming exercise reduced the vasoconstrictor potency
      of phenylephrine in the studied arteries, regardless of the presence of intact
      endothelium. No significant changes were observed in the maximal response to
      phenylephrine. Treatment with indomethacin (1 microM) did not affect the exercise
      induced reduction in vascular responsiveness to phenylephrine. However, the
      reduction of vascular reactivity to phenylephrine due to repeated exercise was no
      longer observed after treatment with N(G)-monomethyl-L-arginine (L-NMMA, 100
      microM). The results suggest that repeated exercise reduces vasomotor responses
      to phenylephrine in rat superior mesenteric arteries through a non-endothelial
      nitric oxide (NO)-related mechanism.

PMID- 15725708
TI  - Dual concentration-dependent effects of phorbol 12, 13-dibutyrate on spontaneous
      and acetylcholine-induced electrical responses recorded from isolated circular
      smooth muscle of the guinea-pig stomach antrum.
AB  - Intracellular recordings of electrical activity were made from circular smooth
      muscle cells in small segments of tissue isolated from the guinea-pig stomach
      antrum. Every cell that was impaled exhibited a rhythmic generation of slow
      potentials. Experiments were carried out to test the effects of three different
      concentrations (1, 10 and 100 nM) of phorbol 12, 13-dibutyrate (PDBu) on these
      slow potentials and on the responses produced by acetylcholine (ACh), in the
      presence of nifedipine and N(omega)-nitro-L-arginine (nitroarginine), known
      inhibitors of L-type Ca-channels and nitric oxide synthase, respectively. The
      resting membrane potential was -62 +/- 7 mV, while the frequency and amplitude of
      the slow potentials were 1.6 +/- 0.1 cycle per min (cpm) and 33 +/- 1 mV,
      respectively. Application of 1 nM PDBu increased the frequency of slow
      potentials, with no significant change in the membrane potential and amplitude of
      slow potentials. At a concentration of 100 nM, PDBu depolarized the membrane by
      about 6 mV, and either decreased the amplitude and frequency of the slow
      potentials or abolished them. The amplitude and frequency of the slow potentials
      were not significantly changed in the presence of 10 nM PDBu. In the presence of
      chelerythrine (1-2 microM), a known inhibitor of protein kinase C (PKC), the
      increase in frequency of slow potentials by 1 nM PDBu and depolarization produced
      by 100 nM PDBu were not elicited. The increase in frequency of slow potentials by
      100 nM ACh was inhibited by PDBu, in a concentration-dependent manner, and ACh
      responses were abolished in the presence of 100 nM PDBu. These results indicate
      that PDBu has dual actions on the spontaneous activity of antral circular muscle,
      with low concentrations increasing and high concentrations inhibiting the
      frequency of the slow potentials. The former may be produced by activation of
      protein kinase C (PKC). As the ACh-induced excitation of slow potentials is
      inhibited by PDBu, a possible causal relationship between the inhibition and over
      activation of PKC is considered.

PMID- 15725710
TI  - [Crohn's disease of the small bowel].

PMID- 15725709
TI  - Electrogastrographic activity in patients who received proximal gastrectomy plus
      jejunal interposition or total gastrectomy plus jejunal interposition.
AB  - Electrogastrograms (EGGs) were recorded in patients both before and after
      receiving proximal gastrectomy plus jejunal interposition (PGJI) or just after
      receiving total gastrectomy plus jejunal interposition (TGJI). Intraluminal
      pressure was also recorded in some postoperative patients. The EGG 3 cpm
      component (2.5-4.9 cpm) remained after PGJI, but subsequently decreased with a
      significant reduction in the preoperative to postoperative ratio of the 3 cpm
      components (P<0.05). The mean frequency of the 3 cpm components increased
      significantly after PGJI (P<0.05) and its instability factor increased. The EGG
      10 cpm components became relatively dominant compared to other frequency
      components in 2 out of 8 of patients having PGJI but the mean amplitude of 10 cpm
      decreased. In TGJI patients, only the 10 cpm component was conspicuous in EGG as
      in the case of total gastrectomy and Roux en Y anastomosis procedures. The
      spectral frequencies of intraluminal pressure in the interposed jejunum were
      similar to the EGG of 10 cpm components both in the case of PGJI and TGJI
      patients. In conclusion, surface EGG could record the electrical activities of
      the interposed jejunum more easily in patients having had TGJI than in PGJI.

PMID- 15725711
TI  - [Hereditary colorectal cancer].
AB  - Hereditary syndromes cause approximately 5 to 15% of overall colorectal cancer
      (CRC) cases. Hereditary CRC is conventionally divided into two major categories:
      hereditary non-polyposis colorectal cancer (HNPCC) and those related to polyposis
      syndromes including familial adenomatous polyposis (FAP), Peutz-Jegher syndrome
      (PJS), and juvenile polyposis (JP). The screening for the cancer and methods of
      treatment applied to patients with hereditary CRC are quite different from those
      applied to the general population. The genes responsible for these syndromes has
      recently identified, as a result, genetic testing has become the most important
      determining factor in clinical decisions. Germ-line mutation of the APC gene
      induces FAP, an autosomal dominant disorder, characterized by the development of
      hundreds to thousands of colonic adenomas. CRC appears in almost all affected
      individuals by the time they are 50 years of age. An affected individual should
      undergo colectomy by his/her late teens. Furthermore, according to the findings
      of genetic testing, at-risk family members also need endoscopic surveillance and
      surgery. Recently, a mutation on the MYH gene is increasingly being investigated
      in patients with multiple polyps, and autosomal recessive MYH polyposis is
      considered to be a new category of polyposis. More common than FAP, HNPCC is
      caused by germ-line mutations in DNA mismatch repair genes, mainly MLH1 and MSH2.
      Although there is no polyposis, polyps seem to be more villous and dysplastic and
      appear to grow rapidly into CRCs. The aggregate lifetime risk of CRC is about 80%
      for mutation carriers. The risk for other types of cancer, such as endometrial,
      ovarian, small bowel, and transitional cell cancer, is also increased. The
      Amsterdam criteria and Bethesda guidelines are the best-known tools for diagnosis
      and genetic testing, and colectomy followed by endoscopic follow-up is the
      standard treatment. PJS and JP are reported to be characterized by hamartomatous
      polyps throughout the GI tract and germ-line mutations in the STK11 gene (PJS)
      and the DPC4/BMPR1A gene (JP).

PMID- 15725712
TI  - [Accuracy of endoscopic ultrasonographic impression compared with pathologic
      diagnosis in gastrointestinal submucosal tumors].
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography (EUS) is a valuable imaging modality
      for the evaluation of gastrointestinal submucosal tumor (SMT). EUS is helpful in
      assessing the layer of origin, tumor diameter, shape, border characteristics, and
      internal echo patterns of SMTs and thus makes it possible to predict histologic
      diagnosis with educated guess. However, some studies have found no significant
      differences in EUS features between benign and malignant mesenchymal tumors. By
      comparing EUS impressions with histologic diagnosis, we evaluated the accuracy of
      EUS in differential diagnosis of gastrointestinal SMTs. METHODS: 58 cases of
      gastrointestinal SMTs with both EUS findings and pathologic reports were compared
      retrospectively from August 2001 to September 2003. RESULTS: 34 patients had
      lesions in the stomach and 13, 8, 3 in the esophagus, duodenum, and colon
      respectively. Benign lesions were predominant (46 of 58). The EUS and pathologic
      diagnosis coincided in 46/58 (79.3%) of the cases. Use of EUS led to the correct
      diagnosis in 7/9 (77.8%) of malignant GISTs (gastrointestinal stromal tumor) and
      leiomyosarcomas. Two small malignant gastric GISTs were diagnosed as benign with
      EUS. CONCLUSIONS: EUS is a useful tool in the differential diagnosis of
      gastrointestinal SMTs and predicting malignant lesions. However, some malignant
      GISTs were diagnosed as benign tumor with EUS examination.

PMID- 15725713
TI  - [Is serum homocysteine level elevated in colorectal tumor?].
AB  - BACKGROUND/AIMS: Although it has been known that folate will participate in
      colorectal carcinogenesis, the relationship between blood folate level and
      colorectal cancer is less consistent. The blood folate level does not reflect the
      systemic folate status. By contrast, serum homocysteine has become a sensitive
      marker for the folate deficiency. We attempted to explain the correlation between
      folate and colorectal cancer according to the serum homocysteine level. METHODS:
      We reviewed the clinical records, including alcohol history of 184 patients
      taking the colonoscopy and measurement of the serum homocysteine level at Health
      Promotion Center from 2001 to 2002. One hundred fifty-one of 184 were included,
      excluding 33 patients with previous history of colonic polyp, cerebrovascular,
      cardiovascular attack and thromboembolism. They were divided into the normal
      control (n=111) and the adenomatous polyp group (n=40). We had selected the
      colorectal cancer group (n=50) from the collection list of the tissue and blood
      bank less than 3 months storage interval. RESULTS: There was no significant
      difference in the mean serum homocysteine level among three groups. However, in
      the subjects with high alcohol consumption, there was a significant difference in
      the mean serum homocysteine between the normal control (n=7) and the adenomatous
      polyp group (n=9) (10.2 vs 15.1 mumol/L, p<0.05). CONCLUSIONS: There was no
      correlation of serum homocysteine and colorectal tumor. However, in the subjects
      with high alcohol consumption, high serum homocysteine might be related to the
      development of adenomatous polyp.

PMID- 15725714
TI  - [Clinical usefulness of glucocorticoid receptor beta expression and NF-kappaB
      activity in patients with ulcerative colitis].
AB  - BACKGROUND/AIMS: Glucocorticoid resistance poses a challenging clinical problem
      in inflammatory bowel disease because more than one fourth of patients with
      severe ulcerative colitis do not respond to anti-inflammatory steroids. Recently,
      it has been reported that glucocorticoid response is related to the expression of
      human glucocorticoid receptor beta (hGRbeta) and nuclear factor-kappa B (NF
      kappaB) activity. The aims of this study were to clarify whether these factors
      may predict the responsiveness before treatment. METHODS: Total RNA was extracted
      from peripheral blood mononuclear cell (PBMC) and colonic mucosa in 17 patients
      of ulcerative colitis before steroid administration. RNA was reverse transcribed
      and the resulting complementary DNA was amplified using specific primers for hGR
      alpha and beta. Concomitantly, NF-kappaB activity in colonic mucosa was assessed
      by immunohistochemical stain. RESULTS: The expression of hGR beta mRNA was
      detected in 10 patients (58.8%) in PBMC and 8 patients (47.1%) in colon,
      respectively. Operations were performed in 5 patients due to steroid
      unresponsiveness. Only 5 of 17 patients (29.4%) were consistent in the expression
      of hGR beta between PBMC and colon. Seven of 15 patients (46.7%) showed an
      alteration in the expression of hGR beta in PBMC after glucocorticoid treatment.
      NF-kappaB activity was found in both epithelial cell and lamina propria in 12,
      epithelial cell alone in 1, lamina propria alone in 1 and all negative in 3
      patients, respectively. CONCLUSIONS: The expression of hGR beta was discordant
      between PBMC and colon in the same patient and showed a change in the expression
      after the glucocorticoid treatment in nearly half. The expression of hGR beta and
      colonic NF-kappaB activity patterns do not provide useful information about
      glucocorticoid response in patients with ulcerative colitis.

PMID- 15725715
TI  - [Trial of moxifloxacin-containing triple therapy after initial and second-line
      treatment failures for Helicobacter pylori infection].
AB  - BACKGROUND/AIMS: Proton-pump inhibitor (PPI)-based triple therapy for
      Helicobacter pylori eradication is widely used with considerable failure rate.
      Bismuth-based, second-line therapy is also associated with failures in more than
      20% of cases in Korea. Our aim was to evaluate the efficacy and tolerability of
      third-line therapy containing moxifloxacin as a rescue in Korea. METHODS: The
      subjects consisted of 201 patients infected with H. pylori, who were treated with
      PPI-based therapy, 42 patients treated with bismuth-based after failure of
      initial PPI triple therapy, and 10 patients treated with moxifloxacin-containing
      triple therapy after failure of successive initial and second-line therapy.
      Eradication rate, compliance and side effect rates were compared. RESULTS: The
      eradication rates of initial, second-line, and third-line therapy were as
      follows: 67.2%/83.3%, 54.8%/76.7%, 80.0%/88.9% by intention-to-treat and per
      protocol analysis, respectively. The compliance of patients for each treatment
      was 98.2%, 90.9%, 100%, respectively. The side effect rate was significantly
      higher in the bismuth triple therapy than in the PPI- or moxifloxacin-containing
      triple therapy (p<0.05). CONCLUSIONS: Moxifloxacin-containing triple therapy
      shows high eradication rate with fewer side effects and good compliance. Thus,
      this regimen could be used as a rescue therapy.

PMID- 15725716
TI  - [Efficacy of hepatic arterial infusion therapy for advanced hepatocellular
      carcinoma using 5-fluorouracil, epirubicin and mitomycin-C].
AB  - BACKGROUND/AIM: Prognosis of advanced hepatocellular carcinoma (HCC) treated by
      conventional therapies has been considered to be poor. The aim of this study was
      to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using FEM (5
      fluorouracil, epirubicin, mitomycin-C) regimen for advanced HCC. METHODS:
      Eighteen patients received repeated HAIT using an implanted drug delivery system.
      Of the 18 patients, 8 patients had HCC with portal vein tumor thrombosis, 9
      patients had recurrent HCC after transarterial chemoembolization (TACE) and 1
      patient after surgical resection. The patients received 5-fluorouracil (330
      mg/m(2), every week), epirubicin (30 mg/m(2), every 4 weeks) and mitomycin-C (2.7
      mg/m(2), every 2 weeks). RESULTS: Mean age was 51 years. The response rate
      (complete response+partial response) by tumor size on abdominal CT was 38.9%.
      Survival ranged from 2 to 24 months and the median survival time was 8 months.
      The cumulative survival rate of responders group was significantly higher than
      non-responders group (p=0.0385). The mean levels of serum alpha-FP and PIVKA-II
      in responders group decreased after HAIT (3,179 ng/mL and 2,850 ng/mL) than
      before (11,218 ng/mL and 4,396 ng/mL), but not significantly. Chemotherapy
      related side effects were nausea, vomiting and alopecia. Three patients had
      catheter-related complications. One patient developed gastric ulcer. CONCLUSIONS:
      HAIT using FEM regimen is a useful therapeutic option for patients with advanced
      HCC with portal vein tumor thrombosis or ineffective response to other therapies.

PMID- 15725717
TI  - [Pancreatic enzyme elevations in Korean chronic renal failure patients].
AB  - BACKGROUND/AIMS: Increased levels of pancreatic enzymes have been reported in
      patients with renal insufficiency even in the absence of pancreatic diseases.
      Here, we analyzed serum amylase and lipase levels in chronic renal failure
      patients according to the degree of azotemia and the treatment modality. METHODS:
      Serum amylase and lipase levels were reviewed in 95 patients on continuous
      ambulatory peritoneal dialysis, 105 patients on hemodialysis, 71 patients with
      renal transplantation, and 73 patients without treatment. Age and sex matched 344
      normal healthy controls were selected among those who checked their serum amylase
      and lipase levels during the same study period. RESULTS: Mean value of amylase
      level in the patient group (93.7+/-76.5 U/L) was higher than healthy controls
      (63.8+/-21.4 U/L) (p<0.001) and lipase level in the patient group (212.3+/-195.0
      U/L) was higher than healthy control (95.2+/-45.1 U/L) (p<0.001). There was no
      significant difference in amylase and lipase levels according to the treatment
      modality in the patient group. The correlations between creatinine clearance and
      amylase (r=-0.148, p=0.012) or lipase (r=-0.119, p=0.042) were found to be
      inverse only when the creatinine clearance falls below 50 mL/min. CONCLUSIONS:
      Serum amylase and lipase levels are about 1.5 times and 2.2 times higher in
      chronic renal failure patients than healthy controls regardless of treatment
      modality. The elevations of amylase and lipase levels are inversely correlated
      with creatinine clearance when it falls below 50 mL/min.

PMID- 15725718
TI  - [A case of R122H mutation of cationic trypsinogen gene in a pediatric patient
      with hereditary pancreatitis complicated by pseudocyst and hemosuccus
      pancreaticus].
AB  - Hereditary pancreatitis is a rare autosomal dominant inherited disease with 80%
      penetration rate. The disease is characterized by recurrent episodes of
      pancreatitis often beginning in childhood, positive family history with at least
      two other affected members and no known precipitating factors. Most forms of
      hereditary pancreatitis are caused by one of two commoner mutations, R122H in
      exon 3 and N29I in exon 2 of the cationic trypsinogen (CT) (PRSS1) gene, located
      on chromosome 7. These genetic defects are speculated to cause excessive trypsin
      activity or to prevent inactivation of prematurely activated trypsin, resulting
      in pancreatitis. We performed mutation analysis of a Korean family with two
      members having clinically suspicious hereditary pancreatitis. We analyzed the CT
      gene in DNA samples extracted from peripheral blood of five family members. First
      of all, polymerase chain reaction and restriction enzyme digestion were performed
      in exon 3 of the CT gene. And then DNA products were purified and sequenced. We
      found out that three members of the family, the mother and two daughters, had a
      R122H mutation of the CT gene. We report the first family of hereditary
      pancreatitis associated with the CT gene mutation, an arginine to histidine amino
      acid substitution at residue 122, in Korea.

PMID- 15725719
TI  - [Two cases of Fitz-Hugh-Curtis syndrome in acute phase].
AB  - Fitz-Hugh-Curtis syndrome has been defined as perihepatitis accompanying pelvic
      inflammatory disease caused by Neisseria gonorrhoeae and Chlamydia trachomatis.
      In the acute phase, patients usually complain of severe right upper quadrant pain
      of sudden onset. The pain is sharp, pleuritic and most intense at the level of
      the right lower rib margin and thus it is frequently confused with acute
      cholecystitis or pleurisy. Definitive diagnosis of Fitz-Hugh-Curtis syndrome
      needs invasive procedures such as laparoscopy or laparotomy, but considering that
      Fitz-Hugh-Curtis syndrome is a benign condition that can be cured by oral
      administration of appropriate antibiotics, noninvasive diagnosis is desirable.
      Recently, we have experienced two cases of Fitz-Hugh-Curtis syndrome in acute
      phase accompanied with sharp and pleuritic right upper quadrant pain. In one
      case, pelvic inflammatory disease was not definite, so at first we mistook it for
      acute cholecystitis and reactivation of chronic hepatitis B. In the other case,
      Fitz-Hugh-Curtis syndrome followed the preceding, typical pelvic inflammatory
      disease. Both cases were diagnosed noninvasively and treated successfully by oral
      administration of antibiotics.

PMID- 15725720
TI  - [Hereditary pancreatitis].
AB  - Hereditary pancreatitis (HP) is an autosomal dominant inherited disease
      characterized by recurrent episodes of pancreatitis often beginning in childhood,
      a family history of at least 2 other affected members, and the absence of known
      etiologic factors. The discovery of mutations in cationic trypsinogen gene
      (PRSS1) in HP not only provided insights into the molecular mechanisms of
      pancreatitis, but also opened a new era in the field of chronic pancreatitis. The
      detection of mutations in serine protease inhibitor, Kazal type 1 (SPINK1) and
      CFTR in patients with hereditary or idiopathic chronic pancreatitis has placed
      the emphasis on the importance of genetic mutations in pancreatitis. Because the
      estimated cumulative risk of pancreatic cancer development in hereditary
      pancreatitis is nearly 40%, screening tests are important in selected cases.
      There are no specific medical therapies recommended in patients with HP.
      Registration of patients with Nationwise Registries is essential if management
      strategies are to be improved and genetic research to be continued.

PMID- 15725722
TI  - Was Warburg right? Or was it that simple?

PMID- 15725723
TI  - Steady states and oscillations in the p53/Mdm2 network.
AB  - p53 is activated in response to events compromising the genetic integrity of a
      cell. Recent data show that p53 activity does not increase steadily with genetic
      damage but rather fluctuates in an oscillatory fashion. Theoretical studies
      suggest that oscillations can arise from a combination of positive and negative
      feedbacks or from a long negative feedback loop alone. Both negative and positive
      feedbacks are present in the p53/Mdm2 network, but it is not known what roles
      they play in the oscillatory response to DNA damage. We developed a mathematical
      model of p53 oscillations based on positive and negative feedbacks in the
      p53/Mdm2 network. According to the model, the system reacts to DNA damage by
      moving from a stable steady state into a region of stable limit cycles.
      Oscillations in the model are born with large amplitude, which guarantees an all
      or-none response to damage. As p53 oscillates, damage is repaired and the system
      moves back to a stable steady state with low p53 activity. The model reproduces
      experimental data in quantitative detail. We suggest new experiments for
      dissecting the contributions of negative and positive feedbacks to the generation
      of oscillations.

PMID- 15725724
TI  - Aging, stem cells and tissue regeneration: lessons from muscle.
AB  - With age, there is a gradual decline in the regenerative properties of most
      tissues due to a combination of age-dependent changes in tissue-specific stem
      cells and in the environmental cues that promote those cells to participate in
      tissue maintenance and repair. In adult skeletal muscle, where the resident
      dedicated stem cells ("satellite cells") are capable of rapid and highly
      effective regeneration in response to injury, there is just such a loss of
      regenerative potential with age. Satellite cell activation and cell fate
      determination are controlled by the Notch signaling pathway that is initiated by
      the rapid increase in expression of the Notch ligand, Delta, following injury. In
      old muscle, this upregulation of Delta is blunted and thus satellite cell
      activation is markedly diminished. However, by indirectly inducing Notch
      activity, the regenerative potential of aged satellite cells can be restored.
      Furthermore, exposure of aged satellite cells to serum from young mice, either in
      vivo by heterochronic parabiotic pairings or in vitro, rejuvenates the satellite
      cell response. This restorative potential suggests that tissue-specific stem
      cells do not lose their ability to participate in tissue maintenance and repair.
      Therefore, it may be that even very old stem cells may be capable of maintaining
      and repairing aged tissues if provided with optimal environmental cues.

PMID- 15725725
TI  - Nuclear positioning, gene activity and cancer.
AB  - In the interphasic nucleus, chromosomes are non-randomly arranged within the
      nuclear space. Indeed, chromosomes are thought to be organised into "chromosome
      territories". The size of a chromosome territory is roughly determined by its DNA
      content, but is also influenced by other factors, such as their transcriptional
      status. Chromatin modifications and positioning of genetic loci in the nucleus
      play a critical role in the control of gene expression. Emerging evidence
      suggests that the nucleus is structurally and functionally compartimentalized and
      desorganization of such a structure might play a major role in the emergence of
      human diseases such as cancer.

PMID- 15725726
TI  - Overview of cell death signaling pathways.
AB  - Apoptosis plays an important role in development and maintenance of tissue
      homeostasis. Intensive efforts have been made to explore the molecular mechanisms
      of the apoptotic signaling pathways including the initiation, mediation,
      execution and regulation of apoptosis. Caspases are central effectors of
      apoptosis. Cells undergo apoptosis through two major pathways, namely the
      extrinsic pathway (death receptor pathway) or the intrinsic pathway (the
      mitochondrial pathway). Finally, the contents of dead cells are packaged into
      apoptotic bodies, which are recognized by neighboring cells or macrophages and
      cleared by phagocytosis. Cellular apoptosis is tightly controlled by a complex
      regulatory networks including balancing pro-survival signals. De-regulation of
      apoptosis may lead to pathological disorders such as developmental defects,
      autoimmune diseases, neurodegeneration or cancer. Increasing attention is being
      focused on alternative signaling pathways leading to cell death including
      necrosis, autophagy, and mitotic catastrophe. Understanding of cell death
      signaling pathways is relevant to understanding cancer and to developing more
      effective therapeutics.

PMID- 15725727
TI  - The road to survival goes through PARG.
AB  - Unlike poly(ADP-ribose) polymerase-1 (PARP-1), poly(ADP-ribose) glycohydrolase
      (PARG) has long been a difficult protein to study. However, the complete absence
      of PARG activity was recently characterized in mice via disruption of the murine
      PARG gene. As expected, PARG is critical for the maintenance of steady-state
      poly(ADP-ribose) levels. But surprisingly, the disruption of PARG led to
      embryonic lethality and increased susceptibility to mild cell stress. Therefore,
      the protective role of PARG and its involvement in development indicate that
      these roads to viability go through PARG.

PMID- 15725728
TI  - Netrin-integrin signaling in epithelial morphogenesis, axon guidance and vascular
      patterning.
AB  - Netrins and their classical receptors--DCC and neogenin--play key roles in
      neuronal guidance. Recent developments identify new roles for netrins in
      epithelial and vascular morphogenesis. Netrins accomplish these effects, at least
      in part, through binding to integrins and/or activating integrin-associated
      kinases such as FAK and Fyn. Here we discuss these recent findings and propose
      that integrins and classical netrin receptors cooperate to regulate multiple
      aspects of development.

PMID- 15725729
TI  - Transcriptional expression of RPMS1 in nasopharyngeal carcinoma and its oncogenic
      potential.
AB  - The Epstein-Barr virus (EBV) BamHI A rightward transcripts (BARTs) were
      originally identified in C15 xenograft of nasopharyngeal carcinoma (NPC) and
      easily detected in a wide variety of EBV latent infection and EBV-associated
      tumors. It had been reported that p31 cosmid containing BARTs immortalized monkey
      epithelial cells, but which particular gene among BARTs family participates in
      the transformation procedure remains to be identified. RPMS1 is the only full
      length cDNA confirmed so far and one of the most abundant spliced forms in BARTs
      family. To investigate the involvement of RPMS1 gene in NPC, we examined the
      expression of RPMS1 transcripts in NPC biopsies from Guangdong and its oncogenic
      potential. Our results revealed that RPMS1 mRNA preferentially expressed in
      primary NPC to non-carcinoma tissue of nasopharynx and peripheral blood
      lymphocytes (PBLs) of NPC patients. Furthermore, by introducing RPMS1 ORF into
      HEK293 cells, these transfectants enhanced the anchorage-independent growth and
      produced tumors in nude mice. These data imply that RPMS1 gene might play an
      important role in the development of NPC.

PMID- 15725730
TI  - Mining genetic epidemiology data with Bayesian networks application to APOE gene
      variation and plasma lipid levels.
AB  - There is a critical need for data-mining methods that can identify SNPs that
      predict among individual variation in a phenotype of interest and reverse
      engineer the biological network of relationships between SNPs, phenotypes, and
      other factors. This problem is both challenging and important in light of the
      large number of SNPs in many genes of interest and across the human genome. A
      potentially fruitful form of exploratory data analysis is the Bayesian or Belief
      network. A Bayesian or Belief network provides an analytic approach for
      identifying robust predictors of among-individual variation in a disease
      endpoints or risk factor levels. We have applied Belief networks to SNP variation
      in the human APOE gene and plasma apolipoprotein E levels from two samples: 702
      African-Americans from Jackson, MS, and 854 non-Hispanic whites from Rochester,
      MN. Twenty variable sites in the APOE gene were genotyped in both samples. In
      Jackson, MS, SNPs 4036 and 4075 were identified to influence plasma apoE levels.
      In Rochester, MN, SNPs 3937 and 4075 were identified to influence plasma apoE
      levels. All three SNPs had been previously implicated in affecting measures of
      lipid and lipoprotein metabolism. Like all data-mining methods, Belief networks
      are meant to complement traditional hypothesis-driven methods of data analysis.
      These results document the utility of a Belief network approach for mining large
      scale genotype-phenotype association data.

PMID- 15725731
TI  - The URMS-RMS hybrid algorithm for fast and sensitive local protein structure
      alignment.
AB  - We present an efficient and sensitive hybrid algorithm for local structure
      alignment of a pair of 3D protein structures. The hybrid algorithm employs both
      the URMS (unit-vector root mean squared) metric and the RMS metric. Our algorithm
      searches efficiently the transformation space using a fast screening protocol;
      initial transformations (rotations) are identified using the URMS algorithm.
      These rotations are then clustered and an RMS-based dynamic programming algorithm
      is invoked to find the maximal local similarities for representative rotations of
      the clusters. Statistical significance of the alignments is estimated using a
      model that accounts for both the score of the match and the RMS. We tested our
      algorithm over the SCOP classification of protein domains. Our algorithm performs
      very well; its main advantages are that (1) it combines the advantages of the RMS
      and the URMS metrics, (2) it searches extensively the transformation space, (3)
      it detects complex similarities and structural repeats, and (4) its results are
      symmetric. The software is available for download at
      biozon.org/ftp/software/urms/.

PMID- 15725732
TI  - A pairwise alignment algorithm which favors clusters of blocks.
AB  - Pairwise sequence alignments aim to decide whether two sequences are related and,
      if so, to exhibit their related domains. Recent works have pointed out that a
      significant number of true homologous sequences are missed when using classical
      comparison algorithms. This is the case when two homologous sequences share
      several little blocks of homology, too small to lead to a significant score. On
      the other hand, classical alignment algorithms, when detecting homologies, may
      fail to recognize all the significant biological signals. The aim of the paper is
      to give a solution to these two problems. We propose a new scoring method which
      tends to increase the score of an alignment when "blocks" are detected. This so
      called Block-Scoring algorithm, which makes use of dynamic programming, is worth
      being used as a complementary tool to classical exact alignments methods. We
      validate our approach by applying it on a large set of biological data. Finally,
      we give a limit theorem for the score statistics of the algorithm.

PMID- 15725733
TI  - Parameter estimation for a mathematical model of the cell cycle in frog eggs.
AB  - Parameter values for a kinetic model of the nuclear replication-division cycle in
      frog eggs are estimated by fitting solutions of the kinetic equations (nonlinear
      ordinary differential equations) to a suite of experimental observations. A set
      of optimal parameter values is found by minimizing an objective function defined
      as the orthogonal distance between the data and the model. The differential
      equations are solved by LSODAR and the objective function is minimized by
      ODRPACK. The optimal parameter values are close to the "guesstimates" of the
      modelers who first studied this problem. These tools are sufficiently general to
      attack more complicated problems, where guesstimation is impractical or
      unreliable.

PMID- 15725734
TI  - Motif-based protein sequence classification using neural networks.
AB  - We present a system for multi-class protein classification based on neural
      networks. The basic issue concerning the construction of neural network systems
      for protein classification is the sequence encoding scheme that must be used in
      order to feed the neural network. To deal with this problem we propose a method
      that maps a protein sequence into a numerical feature space using the matching
      scores of the sequence to groups of conserved patterns (called motifs) into
      protein families. We consider two alternative ways for identifying the motifs to
      be used for feature generation and provide a comparative evaluation of the two
      schemes. We also evaluate the impact of the incorporation of background features
      (2-grams) on the performance of the neural system. Experimental results on real
      datasets indicate that the proposed method is highly efficient and is superior to
      other well-known methods for protein classification.

PMID- 15725735
TI  - An efficient algorithm to compute the landscape of locally optimal RNA secondary
      structures with respect to the Nussinov-Jacobson energy model.
AB  - We make a novel contribution to the theory of biopolymer folding, by developing
      an efficient algorithm to compute the number of locally optimal secondary
      structures of an RNA molecule, with respect to the Nussinov-Jacobson energy
      model. Additionally, we apply our algorithm to analyze the folding landscape of
      selenocysteine insertion sequence (SECIS) elements from A. Bock (personal
      communication), hammerhead ribozymes from Rfam (Griffiths-Jones et al., 2003),
      and tRNAs from Sprinzl's database (Sprinzl et al., 1998). It had previously been
      reported that tRNA has lower minimum free energy than random RNA of the same
      compositional frequency (Clote et al., 2003; Rivas and Eddy, 2000), although the
      situation is less clear for mRNA (Seffens and Digby, 1999; Workman and Krogh,
      1999; Cohen and Skienna, 2002),(1) which plays no structural role. Applications
      of our algorithm extend knowledge of the energy landscape differences between
      naturally occurring and random RNA. Given an RNA molecule a(1), ... , a(n) and an
      integer k > or = 0, a k-locally optimal secondary structure S is a secondary
      structure on a(1), ... , a(n) which has k fewer base pairs than the maximum
      possible number, yet for which no basepairs can be added without violation of the
      definition of secondary structure (e.g., introducing a pseudoknot). Despite the
      fact that the number numStr(k) of k-locally optimal structures for a given RNA
      molecule in general is exponential in n, we present an algorithm running in time
      O(n (4)) and space O(n (3)), which computes numStr(k) for each k. Structurally
      important RNA, such as SECIS elements, hammerhead ribozymes, and tRNA, all have a
      markedly smaller number of k-locally optimal structures than that of random RNA
      of the same dinucleotide frequency, for small and moderate values of k. This
      suggests a potential future role of our algorithm as a tool to detect noncoding
      RNA genes.

PMID- 15725736
TI  - An efficient algorithm for sorting by block-interchanges and its application to
      the evolution of vibrio species.
AB  - In the study of genome rearrangement, the block-interchanges have been proposed
      recently as a new kind of global rearrangement events affecting a genome by
      swapping two nonintersecting segments of any length. The so-called block
      interchange distance problem, which is equivalent to the sorting-by-block
      interchange problem, is to find a minimum series of block-interchanges for
      transforming one chromosome into another. In this paper, we study this problem by
      considering the circular chromosomes and propose a Omicron(deltan) time algorithm
      for solving it by making use of permutation groups in algebra, where n is the
      length of the circular chromosome and delta is the minimum number of block
      interchanges required for the transformation, which can be calculated in
      Omicron(n) time in advance. Moreover, we obtain analogous results by extending
      our algorithm to linear chromosomes. Finally, we have implemented our algorithm
      and applied it to the circular genomic sequences of three human vibrio pathogens
      for predicting their evolutionary relationships. Consequently, our experimental
      results coincide with the previous ones obtained by others using a different
      comparative genomics approach, which implies that the block-interchange events
      seem to play a significant role in the evolution of vibrio species.

PMID- 15725737
TI  - Stem cells in vascular development.

PMID- 15725738
TI  - Peripheral blood stem cell mobilization and harvesting after fludarabine therapy
      for low-grade lymphoma and chronic lymphocytic leukemia.

PMID- 15725739
TI  - Cord blood processing by using a standard manual technique and automated closed
      system "Sepax" (Kit CS-530).

PMID- 15725740
TI  - "Waste" follicular aspirate from fertility treatment--a potential source of human
      germline stem cells?
AB  - Fertility clinics worldwide routinely produce a large volume of 'waste'
      follicular aspirate, which is potentially an abundant source of immature ovarian
      follicles. Current attempts to cultivate these further in vitro to yield viable
      mature oocytes for fertility treatment have not yet achieved much success.
      Instead, recent lines of evidence have emerged that are suggestive of a potential
      stem cell niche within such immature ovarian follicles. The recent discovery of
      follicular renewal and putative germ-line stem cells within the postnatal
      mammalian ovary shook the foundations of reproductive biology by challenging the
      established dogma that mammalian females lose the capacity for germ cell renewal
      during fetal life, such that a fixed reserve of germ cells (oocytes) enclosed
      within follicles is endowed at birth. More intriguingly, another recent study in
      the Drosophila model provided compelling evidence that somatic progenies (nurse
      cells) of germ-line stem cells had the ability to revert back to the stem-cell
      like state. This introduces the exciting possibility that within the mammalian
      ovarian follicle, similar somatic progenies of germ-line stem cells may also
      possess a greater intrinsic ability to revert back into functional stem cells. If
      this is the case, then a favored candidate would be the cumulus/granulosa of
      immature ovarian follicles, since such cells are true homologues of nurse cells
      found within the Drosophila ovary. The successful elucidation of a human germ
      line stem cell niche within immature ovarian follicles is likely to have huge
      ramifications in stem cell biology and regenerative medicine.

PMID- 15725741
TI  - Are stem cell characteristics altered by disease state?
AB  - Autologous stem cell transplantation combined with gene therapy can potentially
      be used to treat genetically inherited diseases. However, characterization of
      multipotential cells from a disease state remains extremely limited. We have
      characterized adult bone marrow stromal cells (MSCs) derived from three retinal
      degenerative mouse models and compared them to marrow stromal cells derived from
      their normal strain counterparts. Despite similar profiles soon after harvest, at
      30 days postisolation, marrow stromal cells derived from a disease origin were
      shown to contain a large pool (approximately 89-99%) of undifferentiated marrow
      stromal cells (CD90(+)/STRO-1(+)) as compared to their normal counterparts
      (approximately 19-43%). Fetal bovine serum appeared essential for marrow stromal
      cell proliferation and was not found to induce differentiation, although it could
      be substituted with other additives including epidermal growth factor (EGF),
      platelet-derived growth factor (PDGF), and leukemia inhibitory factor (LIF). We
      also showed that resulting CD90(+)/STRO(+) cells derived from both states could
      be directed into desired lineages expressing at the same rate and that they could
      be transduced with the same efficiency using different viral vehicles. This
      investigation has shown the existence of a large pool of undifferentiated stem
      cells derived from the disease state that have the potential to form the desired
      cell types when appropriately cued.

PMID- 15725742
TI  - Tumorigenicity issues of embryonic carcinoma-derived stem cells: relevance to
      surgical trials using NT2 and hNT neural cells.
AB  - Cell therapy is a rapidly moving field with new cells, cell lines, and tissue
      engineered constructs being developed globally. As these novel cells are further
      developed for transplantation studies, it is important to understand their safety
      profiles both prior to and posttransplantation in animals and humans. Embryonic
      carcinoma-derived cells are considered an important alternative to stem cells.
      The NTera2/D1 teratocarcinoma cell-line (or NT2-N cells) gives rise to neuron
      like cells called hNT neurons after exposure to retinoic acid. NT2 cells form
      tumors upon transplantation into the rodent. However, when the NT2 cells are
      treated with retinoic acid to produce hNT cells, they terminally differentiate
      into post-mitotic neurons with no sign of tumorigenicity. Preliminary human
      transplantation studies in the brain of stroke patients also demonstrated a lack
      of tumorigenicity of these cells. This review focuses on the use of hNT neurons
      in cell transplantation for the treatment in central nervous system (CNS)
      diseases, disorders, or injuries and on the mechanism involved in retinoic acid
      exposure, final differentiation state, and subsequent tumorigenicity issues that
      must be considered prior to widespread clinical use.

PMID- 15725743
TI  - Endothelial cells in the early murine yolk sac give rise to CD41-expressing
      hematopoietic cells.
AB  - Hematopoietic and endothelial cells may be derived from a common precursor cell
      (hemangioblast) during embryogenesis; however, some evidence suggests that
      hematopoietic cells may emerge from endothelial cells. The onset of definitive
      hematopoiesis at E8.25 in the murine embryo is marked by high-level CD41
      expression. We questioned whether these hematopoietic cells were derived directly
      from mesoderm cells or emerged from endothelium. At 8.25 days post coitus (dpc),
      CD41 was coexpressed with CD31, CD34, and Flk1 in some intraluminal round cells
      that appeared to arise from flattened endothelial cells lining yolk sac capillary
      vessels. Cell-sorting studies revealed that all subpopulations of cells
      expressing CD41 possessed hematopoietic activity. Surprisingly, Tie2(+)Flk1(+)
      cells, a phenotype enriched in adult endothelial progenitors, also displayed some
      hematopoietic progenitor activity in vitro, but this activity was restricted to
      the CD41(+) fraction; only endothelial cells were derived from freshly isolated
      Tie2 (+)Flk1(bright) CD41() cells. Tie2(+)Flk1(dim)CD41() 8.25-dpc yolk sac cells
      devoid of hematopoietic progenitor activity gave rise to endothelial-like
      capillary networks in vitro and differentiated upon co-culture with OP9 stromal
      cells into definitive hematopoietic progenitors. These results demonstrate that
      CD41-expressing definitive hematopoietic cells appear to arise from endothelial
      cells lining nascent capillaries in vivo.

PMID- 15725744
TI  - High-purity lineage selection of embryonic stem cell-derived neurons.
AB  - The derivation of somatic cell types from pluripotent and self-renewing embryonic
      stem (ES) cells offers attractive prospects for basic research, compound
      development, and regenerative medicine. A key prerequisite for biomedical
      applications of ES cells is the ability to differentiate and isolate defined
      somatic cell populations at high purity. In this study, we explore the potential
      of the Talpha1- enhanced green fluorescent protein (EGFP) transgene and
      polysialic acid (PSA)-neural cell adhesion molecule (NCAM) as lineage selection
      markers for the derivation of ES cell-derived neurons. Upon controlled in vitro
      differentiation, ES cells engineered to express EGFP under control of the Talpha1
      tubulin promoter exhibited exclusive transgene expression in neurons. Similarly,
      PSA-NCAM expression during the early stages of ES cell differentiation was
      restricted to neuronal progeny. Talpha1- EGFP- and PSA-NCAM-positive neurons
      comprised both inhibitory and excitatory phenotypes. Compared to Talpha1-EGFP,
      the expression of PSA-NCAM was initiated at slightly earlier stages of neural
      differentiation. FACSorting of Talpha1-EGFP-positive cells and immunopanning of
      PSA-NCAMexpressing cells yielded neuronal populations at purities up to 99.6% and
      96.9%, respectively. These findings depict Talpha1-EGFP and PSA-NCAM as suitable
      markers for high-purity selection of early ES cell-derived neurons.

PMID- 15725745
TI  - Neural cell differentiation in vitro from adult human bone marrow mesenchymal
      stem cells.
AB  - Bone marrow (BM) mesenchymal stem cells (MSCs) are cells capable of expanding and
      differentiating in vitro into nonhematopoietic cells. Neurotrophic cytokines,
      such as human epidermal growth factor (hEGF) and bovine fibroblast growth factor
      (bFGF) can induce differentiation into neural cells (NCs). When BM MSCs were
      cultured with hEGF and bFGF, RNA expression of neuronal specific markers Nestin,
      MAP-2, and tyrosine hydroxylase (TH) were observed. We tested a new cytokine
      combination to generate mature NCs. The plastic-adherent cells were collected and
      then split when they were 90% confluent from an enriched mononuclear cell layer.
      At passage 3, MSCs were cultured in neural differentiation media (dbcAMP, IBMX,
      FGF-8, BDNF, hEGF, and bFGF in NEUROBASAL media plus B27). Cells were counted on
      day 6. Immunofluorescent staining and reverse transcriptase (RT)-PCR were
      performed to evaluate the expression of neural markers. On day 6, 66% of cells
      developed dendrites and presented typical neural cell morphology. Some cells were
      positive for early neural markers Nestin and beta-tubulin III. Cells expressing
      mature neuronal markers (NF, NeuN, Tau, Nurr1, GABA, oligodendryte GalC, and
      glial GFAP) were also seen. By adding hEGF, bFGF, dbcAMP, IBMX, BDNF, and bFGF-8
      into NEUROBASAL media plus B27, BM MSCs were directed toward becoming early and
      mature NCs.

PMID- 15725746
TI  - High-potential human mesenchymal stem cells.
AB  - Bone marrow-derived stromal mesenchymal stem cells (MSCs) have been characterized
      in vitro by their growth characteristics, the expression of a panel of surface
      antigens, and their potential to differentiate into mesenchymal lineages. They
      can be separated by physical methods as well as by immunological or chemical
      separation or cultivation. Different protocols are used in different
      laboratories, making the comparison of various reported MSC populations
      difficult. Here we describe a population of bone marrow-derived adult stem cells
      that has been separated on a Percoll gradient with low density. It is
      characterized by an extraordinary high proliferative potential and a conserved
      phenotype characteristic of MSCs that retain their plutipotentiality in culture,
      as evidenced by their ability to differentiate into osteo-, chondro-, and
      adipogenic lineages. Separation of these cells provide an effective and
      convenient method for rapid expansion of pluripotential human MSCs for clinical
      use where large amounts of stem cells are needed.

PMID- 15725748
TI  - Accelerated growth and prolonged lifespan of adipose tissue-derived human
      mesenchymal stem cells in a medium using reduced calcium and antioxidants.
AB  - Human mesenchymal stem cells (MSCs) have been isolated from bone marrow and other
      adult tissues and are potentially useful for tissue engineering. Adipose tissue
      has several clear advantages as a starting material for harvesting stem cells, as
      it is abundant and relatively easy to procure. However, existing methods to
      expand adipose-derived MSCs are less than optimal. Here we describe a new cell
      culture method that accelerates greatly the growth rate and prolongs the lifespan
      of adipose MSCs. This was accomplished by using a growth medium with low calcium
      and supplemented with N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate. Cells
      produced early in these cultures displayed characteristics similar to those
      previously reported for multipotential stem cells, including a high frequency of
      anchorage- independent growth in soft agar, lack of gap junctional intercellular
      communication in a cell type with serpiginous morphology, and the expression of
      Oct-4. Furthermore, these cells could readily be induced to differentiate into
      adipocytes, osteoblasts, and chondrocytes. Thus, modification of growth medium by
      reduction of calcium and addition of antioxidants greatly enhanced the growth
      rate and extended the lifespan of adipose-derived multipotential human MSCs.

PMID- 15725747
TI  - Exposure to nicotine during gestation interferes with the colonization of fetal
      bone marrow by hematopoietic stem/progenitor cells.
AB  - Environmental factors, including cigarette smoke components, can cross the
      placental barrier and accumulate in amniotic fluid and fetal tissue, and,
      therefore, interfere with the normal course of ontogenesis. Although cigarette
      smoke contains numerous compounds, the most adverse effects on mammalian tissues
      have been associated with nicotine. The aim of this study was to investigate the
      effect of intrauterine exposure to nicotine on hematopoiesis during fetal
      development and postpartum. Intrauterine exposure of mice to nicotine resulted in
      a more than two-fold reduction of the delayed- type hypersensitivity (DTH)
      response and a 2.5-fold decrease in the number of plaque forming cell (PFC) in
      offspring after 1 month of postnatal life, and correlated with low counts of
      mature lymphocytes and lymphoid progenitors in hematopoietic tissues. Neonates
      exposed to nicotine during gestation showed a significant decrease in the number
      of bone marrow hematopoietic progenitors, as measured by colony-forming unit
      (CFU) and long-term culture initiating cell (LTC-IC) assays, and decreased
      concentration of interleukin-6 (IL-6) in their serum. Analysis of the fetal bone
      marrow (E15) obtained from nicotine-exposed fetuses demonstrated a lower number
      of hematopoietic progenitors, whereas their number in the fetal liver was not
      significantly changed. Our data provide evidence that by targeting the nicotinic
      acetylcholine receptor (nAChR) nicotine interferes with the fetal development of
      the hematopoietic system. Inferior colonization of the fetal bone marrow by
      hematopoietic stem/progenitor cells (HSPC) subsequently results in an imbalance
      of mature blood and immune cell production after birth.

PMID- 15725749
TI  - Association of CCR5 human haplogroup E with rapid HIV type 1 disease progression.
AB  - The combination of unique single nucleotide polymorphisms in the CCR5 regulatory
      and in the CCR2 and CCR5 coding regions, defined nine CCR5 human haplogroups
      (HH): HHA-HHE, HHF*1, HHF*2, HHG*1, and HHG*2. Here we examined the distribution
      of CCR5 HH and their association with HIV infection and disease progression in 36
      HIV-seronegative and 76 HIV-seropositive whites from North America and Spain [28
      rapid progressors (RP) and 48 slow progressors (SP)]. Although analyses revealed
      that HHE frequencies were similar between HIV-seronegative and HIV-seropositive
      groups (25.0% vs. 32.2%, p > 0.05), HHE frequency in RP was significantly higher
      than that in SP (48.2% vs. 22.9%, p = 0.002). Survival analysis also showed that
      HHE heterozygous and homozygous were associated with an accelerated CD4 cell
      count decline to less than 200 cells/microL (adjusted RH 2.44, p = 0.045;
      adjusted RH = 3.12, p = 0.037, respectively). These data provide further evidence
      that CCR5 human haplogroups influence HIV-1 disease progression in HIV-infected
      persons.

PMID- 15725750
TI  - Ex vivo modeling of the effects of mycophenolic acid on HIV infection:
      considerations for antiviral therapy.
AB  - Mycophenolate mofetil (MMF), the bioavailable form of mycophenolic acid (MPA),
      has been proposed as adjuvant therapy for human immunodeficiency virus type 1
      (HIV-1) infection. MPA can inhibit viral replication and might blunt virus
      induced immunopathology. However, other effects of this inhibitor might be
      detrimental in an HIV-infected patient. We therefore studied the effect of MPA on
      selected cellular processes of relevance to HIV infection. We found that MPA did
      not alter the expression of the primary HIV coreceptor CCR5 on primary resting
      lymphocytes, but modestly increased CCR5 expression after activation. Conversely,
      MPA modestly decreased the secretion of the CCR5 ligand RANTES in resting
      lymphocytes, but had no effect after activation. It has been suggested that the
      use of inhibitors of host nucleoside metabolism may enhance clinical toxicities
      induced by HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs). We found no
      evidence that MPA induced mitochondrial dysfunction or enhanced dysfunction
      induced by NRTIs in an HepG2 cell line model of mitochondrial toxicity. Further,
      MPA did not selectively enhance apoptosis in HIV-1-infected lymphocytes. Our
      findings support the testing of MMF to augment suppression of viral replication.
      However, careful study will be required to demonstrate that MMF is beneficial
      when used without antiretroviral therapy, to inhibit residual replication, or to
      deplete the pool of latently infected nonactivated cells.

PMID- 15725751
TI  - Identification of granulocyte-macrophage colony-stimulating factor and
      lipopolysaccharide-induced signal transduction pathways that synergize to
      stimulate HIV type 1 production by monocytes from HIV type 1 transgenic mice.
AB  - HIV-1-infected monocyte/macrophages located in lymph nodes and tissues are highly
      productive sources of HIV-1 and may function as a persistent reservoir
      contributing to the rebound viremia observed after highly active antiretroviral
      therapy is stopped. Mechanisms activating latently infected, primary
      monocyte/macrophages to produce HIV-1 were investigated using monocytes isolated
      from a transgenic mouse line carrying a full-length proviral clone of a monocyte
      tropic HIV-1 isolate, HIV-1(JR-CSF), regulated by the endogenous long terminal
      repeat (LTR) (JR-CSF mice). Granulocyte-macrophage colony-stimulating factor (GM
      CSF) combined with lipopolysaccharide (LPS) induced infectious HIV-1 production
      by JR-CSF mouse monocytes over 10-fold and 100-fold higher than that stimulated
      by GM-CSF or LPS alone, respectively. We examined mechanisms of GM-CSF synergy
      with LPS and demonstrated that GM-CSF up-regulated the LPS receptor, TLR-4, and
      also synergized with LPS to activate mitogen-activated protein (MAP) kinase/ERK
      kinase and the Sp1 transcription factor. Inhibitors of either MAP kinase/ERK
      kinase or p38 kinase but not PI 3-kinase potently suppressed GM-CSF and LPS
      induced HIV-1 production by JR-CSF mouse monocytes. Because Sp1 is activated by
      both the MAP kinase/ERK kinase and p38 kinase pathways, we postulate that
      synergistic activation of these pathways by GM-CSF and LPS induced sufficient
      levels of Sp1 to activate the HIV-1 LTR in a Tat-independent manner and induced
      HIV-1 production by JR-CSF mouse monocytes. Thus, our study delineated the
      pathway of HIV-1 LTR activation by GM-CSF and LPS and indicated that JR-CSF
      transgenic mice may provide a new in vitro and in vivo system for investigating
      the mechanism by which inflammatory and infectious stimuli activate HIV-1
      production from latently infected monocytes.

PMID- 15725752
TI  - Studies in macaques on cross-clade T cell responses elicited by a DNA/MVA AIDS
      vaccine, better conservation of CD8 than CD4 T cell responses.
AB  - One of the unknowns faced by an HIV/AIDS vaccine is the ability of a single clade
      vaccine to protect against the multiple genetic subtypes and recombinant forms of
      HIV-1 present in the current pandemic. Here, we use a macaque model to
      investigate the ability of our clade B vaccine that consists of DNA priming and
      modified vaccinia Ankara (MVA) virus boosting to elicit T cell responses that
      recognize an A/G recombinant of HIV-1. To test for cross-reactive T cells,
      intracellular cytokine staining was conducted using five pools of Gag and six
      pools of Env peptides representing B or A/G sequences. Studies using the peptide
      pools revealed essentially complete conservation of the CD8 response but only
      approximately 50% conservation of the CD4 response. Thus, the ability of an HIV
      vaccine for one clade to protect against other clades may be more limited by the
      ability to provide CD4 T cell help than the ability to elicit CD8 effector
      functions.

PMID- 15725753
TI  - Analysis of full-length human immunodeficiency virus type 1 genome reveals a
      variable spectrum of subtypes B and f recombinants in Sao Paulo, Brazil.
AB  - Recombination is one of the major mechanisms contributing to human
      immunodeficiency virus type 1 (HIV-1) variability. Analysis of pol gene sequences
      of 215 HIV-1 samples from Sao Paulo, Brazil classified 189 sequences as subtype B
      (87.9%), 8 sequences as subtype F (3.7%), and 18 sequences (8.4%) as B/F
      recombinants. After the analysis of the pol gene, a subset of six recombinant
      samples composed of sequences with a related recombinant pol structure was
      selected for full-length genome analysis to identify a possible circulating
      recombinant form. According to full-length genome analysis, recombination was
      higher in gag, protease, reverse transcriptase, integrase, and vif.
      Identification of many distinct recombinant forms and the absence of an
      identifiable HIV-1 circulating recombinant form suggest that a high frequency of
      dual infections between HIV-1 subtypes B and F is occurring in Sao Paulo, Brazil.

PMID- 15725754
TI  - Subtype B and subtype C HIV type 1 recombinants in the northeastern state of
      Manipur, India.
AB  - The predominant HIV-1 strain circulating in India is subtype C. However, subtype
      A and B strains of HIV-1 have also been reported in India. In 1999, the first A/C
      recombinant strain was reported from Pune in India. Intravenous drug users
      (IVDUs) from the northeastern region of India have a high HIV-1 seroprevalence.
      Studies carried out in intravenous drug users in the northeastern region of India
      have shown that HIV-1 subtype C is the predominant strain infecting IVDUs.
      Fourteen blood samples were collected from HIV-1-infected individuals from the
      northeastern region of India and screened by env and gag heteroduplex mobility
      assays (HMA). Where the env and gag HMA results from a sample yielded different
      subtypes, sequencing of env and gag PCR products was carried out to confirm the
      presence of HIV-1 recombinants. Of the 14 samples subtyped, nine samples belonged
      HIV-1 subtype C (gag C/env C), one to HIV-1 subtype B (gag B/env B), and the
      remaining were B/C recombinants (gag C/env B). This is the first report of HIV-1
      B/C recombinants from India.

PMID- 15725755
TI  - Circulation of novel HIV type 1 A, B/C, and F subtypes in Argentina.
AB  - The Argentine HIV-1 epidemic is considered to be represented mainly by subtype B
      and diverse B/F recombinants, with apparent absence of pure subtype F. In this
      study we describe three novel HIV-1 variants isolated from four infants born in
      different and distant provinces of Argentina. Partial analysis of different gene
      fragments spanning 18.5-40.8% of the HIV-1 complete genome revealed two subtype A
      HIV-1 strains in siblings, a B/C recombinant with a novel mosaic structure, and a
      putative subtype F. Characteristic patterns of genomic and amino acid sequences
      of the newly reported subtype F isolate suggest a closer genetic relationship to
      Argentine B/F recombinants than any other subtype F strain described so far,
      while the A and B/C subtypes found correspond to unusual genotypes in Argentina.
      Understanding the origin, diversity, and spread of HIV-1 strains worldwide will
      be necessary for the development of an effective vaccine approach.

PMID- 15725756
TI  - T cell epitope "hotspots" on the HIV Type 1 gp120 envelope protein overlap with
      tryptic fragments displayed by mass spectrometry.
AB  - Our previous work has shown that immunodominant T-helper cell epitopes cluster
      within distinct fragments on a single face of the HIV envelope gp120 protein. We
      show in this report that the general positions of immunodominant epitopes are
      shared by T cells derived from BALB/c, C57BL/6, and CB6F1 mice, yet the precise
      peptides recognized by the responding T cell populations may differ. In addition,
      we find that gp120 peptides displayed by tryptic digestion and mass spectrometry
      of a purified HIV envelope protein share location with peptides defined as
      immunodominant T cell targets. Results are consistent with the suggestion that
      gp120 peptide location influences antigen processing, which, in turn, influences
      the specificity of immunodominant T cells.

PMID- 15725757
TI  - V3: HIV's switch-hitter.
AB  - The third variable region, V3, of the gp120 surface envelope glycoprotein is an
      approximately 35-residue-long, frequently glycosylated, highly variable,
      disulfide-bonded structure that has a major influence on HIV-1 tropism. Thus the
      sequence of V3, directly or indirectly, can determine which coreceptor (CCR5 or
      CXCR4) is used to trigger the fusion potential of the Env complex, and hence
      which cells the virus can infect. V3 also influences HIV-1's sensitivity to, and
      ability to escape from, entry inhibitors that are being developed as antiviral
      drugs. For some strains, V3 is a prominent target for HIV-1 neutralizing
      antibodies (NAbs); indeed, for many years it was considered to be the "principal
      neutralization determinant" (PND). Some efforts to use V3 as a vaccine target
      continue to this day, despite disappointing progress over more than a decade.
      Recent findings on the structure, function, antigenicity, and immunogenicity of
      V3 cast new doubts on the value of this vaccine approach. Here, we review recent
      advances in the understanding of V3 as a determinant of viral tropism, and
      discuss how this new knowledge may inform the development of HIV-1 drugs and
      vaccines.

PMID- 15725769
TI  - Age of retinal hemorrhages by iron detection: an animal model.
AB  - Intraretinal hemorrhages have been found in some abusively injured infants and
      children. Intraretinal hemosiderin has been proposed as an indication of previous
      injury. The limits of the accuracy of the proposal have not been established.
      Experimental central retinal vein occlusion (CRVO) was produced in 20 eyes of
      adult rhesus monkeys as part of ongoing research by one of the authors (SSH). The
      animal experiments were conducted in accordance with a research protocol approved
      by the Animal Care Committee, University of Iowa. CRVO produced diffuse
      intraretinal hemorrhages. Clinical ocular examinations assessed the onset and
      time course of retinal hemorrhages. Enucleation specimens were used to assess
      hemosiderin in the retinas. Hemosiderin was detected within 2 days of induction
      of retinal hemorrhages. It was detected in only 4 of 11 eyes (36%) studied more
      than 1 week following induction of hemorrhages. In 2 eyes, hemosiderin was found
      9 and 16.8 months after development of hemorrhages. Hemosiderin can represent
      organization of current hemorrhage rather than evidence of prior hemorrhage. This
      study does not allow specifying the duration of hemorrhages with greater
      precision than "more than 2 days prior to death," and that, only if there is no
      survival interval. Failure to detect hemosiderin does not exclude prior retinal
      hemorrhages.

PMID- 15725770
TI  - Physical forms of contemporary small-arms propellants and their forensic value.
AB  - Intermediate gunshot wounds typically produce powder tattooing and/or stippling
      of the skin. The size and density of such powder-induced injuries around an entry
      wound are used to estimate the separation distance between the muzzle of the
      responsible firearm and the entry site through test firings at selected muzzle-to
      target distances, with ammunition comparable to the injury-producing round and
      the evidence firearm. The foregoing is well known to forensic pathologists who
      document and describe such powder patterns in gunshot victims and firearm
      examiners who customarily produce the test-fired powder patterns for subsequent
      range-of-fire determinations. Less known, particularly to pathologists, is the
      considerable variety in forms of modern nitrocellulose propellants, their effects
      on powder-induced injuries to human skin, and the value of these varied physical
      forms in the reconstruction of shooting incidents. These factors are the subject
      of this article.

PMID- 15725771
TI  - Sudden unexpected death in epilepsy: a retrospective study.
AB  - Patients with epilepsy have a mortality rate higher than that of the general
      population; sudden unexpected death represents a significant category of
      mortality in these patients. The precise frequency of occurrence of sudden
      unexpected death in epilepsy (SUDEP) is not well defined, with a range of 1 in
      370 to 1100 in the general epileptic population. A major difficulty with
      incidence studies is the continued reluctance in using the term SUDEP as a cause
      of death, making reliance solely on death certificates inconsistent and
      incomplete. Knowledge about SUDEP remains limited, as no single common risk
      factor has yet been identified, although predisposing conditions have been
      suggested. The purpose of this study is to review the association between several
      clinical variables and SUDEP to elucidate risk factors. The characteristics of
      the 67 cases in this series correlate with published findings in previous
      studies. Attributes that may be used to define an at-risk group of epileptics
      include age less than 40 years, male gender, long history of seizure disorder,
      undermedication or poorly controlled seizure activity, and mental or physical
      stress. Education of physicians as to the existence of SUDEP and risk factors is
      imperative in improving patient education and reduction in mortality.

PMID- 15725772
TI  - Prevalence of Demodex in health personnel working in the autopsy room.
AB  - The health personnel working in the autopsy rooms and laboratories are considered
      among the professional groups carrying a high risk of contamination with
      infection. In this study, we have investigated the prevalence of Demodex, which
      provides a convenient environment for bacteria and acts as a vector for certain
      microorganisms, in the health personnel working in autopsy rooms. The study,
      which was cross-sectional, was conducted on 58 health personnel working in
      autopsy rooms. A questionnaire was administered to the individuals. Specimens
      were obtained from 4 different regions of the face using the standard skin
      surface biopsy technique. The data obtained were then evaluated statistically.
      This study group consisted of 76% males and 24% females. The prevalence of
      Demodex was 26%. Demodex was found to occur more frequently in women. The most
      frequent occurrence of Demodex was seen among people with darker complexion and
      in cheek localizations. We believe that Demodex, which has a role in the
      pathogenesis of dermatologic diseases, provides a convenient environment for
      bacteria, and acts as a vector for some pathogenic microorganisms, poses a risk
      as far as individuals working in the autopsy room are concerned.

PMID- 15725773
TI  - Alprazolam-related deaths in Palm Beach County.
AB  - Alprazolam is a commonly prescribed benzodiazepine. The abuse of benzodiazepines
      is most frequently seen in conjunction with the abuse of other drugs. Only rare
      fatalities have been attributed to alprazolam alone. We undertook a retrospective
      review of cases investigated by the Palm Beach County Medical Examiner's Office
      in which postmortem toxicologic studies indicated the presence of alprazolam, to
      further study the pattern of alprazolam abuse. Our review consisted of 178 cases,
      including 87 in which death was attributed to combined drug toxicity, 2 to
      alprazolam toxicity alone, 44 to trauma, 12 to natural causes, and 33 to another
      drug or drugs. Cocaine and methadone were the most common cointoxicants in the
      cases of combined drug toxicity, while heroin was less frequently detected. There
      was considerable overlap in the postmortem blood alprazolam concentrations among
      the groups. The overlapping ranges of concentrations of alprazolam detected
      indicate that it may be difficult to define a lethal alprazolam range, and that
      it may not be possible to determine the actual role of alprazolam as a causal
      factor in cases of combined drug toxicity. This study confirms that alprazolam
      alone is rarely a cause of death, and that alprazolam abuse usually occurs within
      a polydrug use pattern. The high incidence of cocaine as a cointoxicant has not
      been previously reported.

PMID- 15725774
TI  - Cosleeping and sudden unexpected infant deaths in Kentucky: a 10-year
      retrospective case review.
AB  - This retrospective case review investigates modifiable risk factors in sudden
      unexpected infant deaths, including those attributed to sudden infant death
      syndrome, and examines the impact of cosleeping with adults or siblings. The
      study examines sudden unexpected infant deaths from 1991 to 2000 in the state of
      Kentucky, excluding homicides and deaths from identifiable natural causes. Meta
      analysis provides a cosleeping prevalence control in normal infants. Based on the
      findings described herein, we conclude that cosleeping may represent a risk
      factor in sudden unexpected infant deaths and that a full scene investigation,
      including whether the infant was cosleeping, should be sought in all cases of
      sudden infant death.

PMID- 15725775
TI  - A qualitative study of compact bone microstructure and nuclear short tandem
      repeat obtained from femur of human remains found on the ground and exhumed 3
      years after death.
AB  - Forensic identification of human remains is composed of anthropological study of
      race, sex, age, etc. By using these traditional methods, inconclusive or
      nonidentified cases could be subjected to DNA analysis. However, in spite of
      advances in human identification techniques, especially by PCR-amplified DNA,
      some limitations that affect the ability of obtaining DNA from human remains
      still persist. Light microscope sections of postmortem compact bones from human
      remains are presented here for the purpose of increasing a forensic examiner's
      prediction of successful nuclear DNA typing. Femoral compact bones were obtained
      from 7 human remains found on the ground, in different degrees of decomposition,
      and were cleaned by boiling to remove soft tissues, 8 collections of bones having
      undergone natural decomposition, not boiled (as no soft tissue was adhered), and
      5 cadavers 12 to 16 hours postmortem. The histologic sections were stained by
      hematoxylin and eosin, the loci CSF1PO, TPOX, TH01, F13A01, FESFPS, vWA, D16S539,
      D7S820, D13S317, and amelogenin were amplified by PCR, and the polyacrylamide gel
      was stained with silver. The results presented here clarify questions concerning
      the viability of DNA for identification analysis, and they also may help to
      establish better strategies for optimization of DNA extraction and analysis in
      compact bones of human remains.

PMID- 15725776
TI  - Autoerotic asphyxia: part I.
AB  - Fatal autoerotic asphyxia refers to death during solitary sexual activity with
      self-induced asphyxiation meant to be brief and reversible. However, an
      unexpected fatality results from a failure of a release mechanism apparatus. The
      large majority of victims of autoerotic death are Caucasian males between the
      second and fourth decade. While autoerotic death may encompass a myriad of other
      means of achieving sexual gratification, which includes asphyxia by plastic bag
      or inhalation of noxious chemicals, the most common method is by ligature about
      the neck. This study presents a 9-year retrospective review of deaths due to
      autoerotic asphyxia, specifically ligature asphyxia, in Kentucky between 1993 and
      2001. Of the sixteen victims, all were Caucasian males between the ages of 14 and
      59 years, with a mean age of 38.3 years. Cross-dressing was a feature in 4 cases.
      A thorough review of the decedent's background, meticulous scene investigation,
      and complete postmortem examination may shed light on the mechanism and
      psychosocial predisposition associated with autoerotic asphyxia.

PMID- 15725777
TI  - Atypical autoerotic death: part II.
AB  - Autoerotic fatalities encompass a wide array of means and mechanisms used to
      attain sexual gratification. The most commonly encountered autoerotic practice,
      specifically, autoerotic asphyxia, denotes death resulting from failure of a
      release mechanism of the apparatus designed to attain cerebral hypoxia for
      heightened arousal. Historically, the majority of victims of autoerotic death are
      Caucasian males under the age of 30. While autoerotic death is most often
      associated with a constrictive cervical ligature tied to either other parts of
      the victim's body or to an inanimate object such as a door, several other methods
      have been reported. These modalities include ligature around the thorax or
      abdomen, plastic bags covering the face, electrical current, inhalation of a
      toxic gas or chemicals, or partial or total submersion, known as aquaerotic
      asphyxiation. This study highlights 11 cases of atypical autoerotic death,
      including asphyxia with a plastic bag, electrocution, and inhalation of butane
      and nitrous oxide (N2O). Whereas the manner of death in the majority of
      autoerotic death cases is deemed accidental, we present and analyze unique and
      equivocal cases representing 4 different manners of death: accident, natural,
      suicide, and homicide. The 11 victims were all Caucasian and between the ages of
      17 and 55. Ten decedents were males, 1 female. A comprehensive investigation
      incorporating a thorough scene analysis, gathering of the victim's history, and
      complete postmortem examination is necessary to elucidate both the cause and
      manner of death in these atypical cases.

PMID- 15725778
TI  - Quality assurance review of death certificates: a pilot study.
AB  - BACKGROUND: Although quality assurance programs for medical examiners are
      required by the National Association of Medical Examiners' Inspection and
      Accreditation Checklist, quality assurance programs specifically targeting death
      certificate completion have not been addressed. The Fulton County Medical
      Examiner, Atlanta, GA, has implemented a pilot quality assurance program for
      death certificate information, and this report contains information about 1
      year's experience with the program. METHODS: All death certificates are reviewed
      by the case medical examiner(s) and chief medical examiner prior to their release
      to funeral homes. Death certificates with errors are retained for quality
      assurance and review purposes, and needed corrections are made before death
      certificates are released. During a 1-year period, death certificates with errors
      were collected and then reviewed and tabulated by type of error. RESULTS: Between
      May 26, 2003, and May 25, 2004, the Fulton County Medical Examiner certified 1267
      deaths. Of these, 47 (4%) were found to contain errors that were corrected and an
      additional 52 (4%) had been amended for various reasons. The most common errors
      were misspellings in causes of death or poor or incomplete wording in injury
      related information. Forty-seven percent of errors involved omitted, incomplete,
      or incorrect information that was potentially significant. The most common reason
      for amended certificates was unexpected detection of acute intoxications among
      people with significant cardiovascular disease. CONCLUSIONS: Quality assurance
      review of death certificates can assist in preventing the release of death
      certificates with incomplete, erroneous, or omitted information and may also be
      useful as an educational forum regarding completion of the death certificate.

PMID- 15725779
TI  - Lightning fatalities on the South African Highveld: a retrospective descriptive
      study for the period 1997 to 2000.
AB  - A review of the Southern Africa medical literature shows a paucity of published
      data regarding lightning fatalities. The South African Highveld has a lightning
      ground flash density of 6 to 9 flashes/km/year, with a high incidence of
      thunderstorm days per year (some 40-70). The Highveld has a largely urban
      population, many of whom have low socioeconomic status and poor education,
      housing, and other infrastructures and hence (possibly) are at greater exposure
      risk. Thirty-eight victims of lightning-related death were identified from the
      records of the 6 large medicolegal mortuaries on the South African Highveld,
      serving a population of approximately 7 million, for the period 1997 to 2000.
      Analysis of the records revealed that 95% of all victims were black, 79% were
      male, and the average age was 36 years. Lightning strikes occurred from September
      through to April (normal summer rainfall period), and the most strikes took place
      in the late afternoon (3:00 pm to 6:00 pm). All except 1 case occurred outdoors.
      In the autopsy reports, mention was made of singeing of hair in 68% of cases, and
      mention of damage to clothing was made in 26% of cases. Cutaneous thermal
      injuries were noted in 34 of the 38 cases, with apparent electrothermal injuries
      of the feet noted in 4 cases. Fifty-two percent of victims sustained some form of
      associated blunt-force injury (including abrasions, contusions, etc). Specific
      keraunopathologic injuries were described in only 2 of the cases. Twenty-one
      cases had some form of internal organ injury. This study serves to illustrate the
      relatively high incidence of lightning strikes in the region and calls for a more
      systematic and detailed investigative protocol in lightning-related deaths.

PMID- 15725780
TI  - Fatal gunshot wounds between 1995 and 2001 in a highly populated region in
      Finland.
AB  - Gunshot injuries are a major problem worldwide from the human, medical, and
      economic perspectives. The number and characteristics of gunshot fatalities have
      been observed to vary significantly between countries. This study analyzes fatal
      gunshot wounds in the region of Uusimaa, Southern Finland, between 1995 and 2001.
      Gunshot wounds were typically found in suicides committed by men aged between 20
      and 60 years. In most cases, a handgun was used. Mental disorders were present in
      the history of almost one quarter of the victims. Alcohol was identified in
      postmortem toxicology in half of the cases, but drugs of abuse were relatively
      uncommon. The autopsy rate in Finland is among the highest of the European Union
      countries, and a medicolegal investigation is performed in virtually all fatal
      gunshot incidents. This study is therefore representative of forensic
      investigations of gunshot fatalities in Finland overall.

PMID- 15725781
TI  - Death due to Ehlers-Danlos syndrome type IV.
AB  - Ehlers-Danlos syndrome (EDS) represents a group of collagen connective tissue
      disorders characterized by joint laxity, easy bruising, and various skin
      manifestations. Persons with type IV EDS are at risk for gastrointestinal,
      uterine, and arterial rupture. Mutations in the COL3A1 gene that encodes for type
      III procollagen underlie the pathologic abnormalities. Forensic pathologists must
      be aware of this rare, autosomal-dominant connective tissue disorder. Postmortem
      diagnosis is possible but requires specialized testing (fibroblast culture and
      subsequent biochemical assays, with or without molecular studies). When the
      condition is diagnosed or suspected at autopsy, it is important for forensic
      pathologists to notify family members of this potentially lethal disorder. Three
      cases of type IV EDS diagnosed by forensic pathologists are presented, followed
      by a discussion of the disorder.

PMID- 15725782
TI  - Sudden, unexpected death due to splenic artery aneurysm rupture.
AB  - Splenic artery aneurysms are an uncommon form of vascular disease that have a
      significant potential for rupture, resulting in life-threatening intraperitoneal
      hemorrhage. We describe the case of a 33-year-old man who died suddenly and
      unexpectedly due to the rupture of a splenic artery aneurysm. At medicolegal
      autopsy, 3000 mL of fluid blood were recovered from the peritoneal cavity. The
      source of bleeding was a sack-like aneurysm of the splenic artery, measuring 2 cm
      in diameter. Histologic examination of the splenic artery aneurysm revealed
      fibromuscular dysplasia. No atherosclerotic lesions or any inflammatory changes
      were apparent within the wall of the splenic artery. Portal hypertension and
      pancreatitis, previously described as important factors promoting splenic artery
      aneurysm formation, were excluded by autopsy and histology. From the forensic
      pathologist's viewpoint, this rare case underlines the importance of splenic
      artery aneurysm rupture as a relevant differential diagnosis of intraperitoneal
      hemorrhage and sudden death, respectively, since such cases may be misinterpreted
      as a result of blunt-force trauma.

PMID- 15725783
TI  - Amitriptyline abuse and misuse.
AB  - Deaths related to amitriptyline toxicity are relatively common and are typically
      related to suicidal overdose. A less well-recognized situation of amitriptyline
      intoxication occurs when the drug is abused for its euphorigenic effects. An
      amitriptyline-related death due to a mixed drug intoxication is presented. Death
      investigation revealed that the death was accidental rather than suicidal. The
      case serves to remind forensic investigators that not all amitriptyline overdose
      deaths represent suicides. A segment of the population is known to abuse
      amitriptyline.

PMID- 15725785
TI  - Ancillary studies in amniotic fluid embolism: a case report and review of the
      literature.
AB  - The incidence of amniotic fluid embolism during pregnancy is approximately
      1/50,000 and has a mortality rate in excess of 80%. The postmortem diagnosis of
      amniotic fluid embolism can be challenging for forensic investigators and
      pathologists. At autopsy, usually signs of disseminated intravascular coagulation
      suggest an amniotic fluid embolism. A definitive diagnosis of amniotic fluid
      embolism cannot be made until ancillary studies are performed on the decedent's
      tissues. We report a case of a 37-year-old G3P2 white female who was 36 weeks
      gestation when her membranes spontaneously ruptured. She suddenly became
      breathless, went into cardiogenic shock, and died. The autopsy revealed gross and
      microscopic findings of amniotic fluid embolism, which was confirmed with
      ancillary studies consisting of special stains, immunohistochemistry, and a serum
      tryptase level. The authors hope this case report, including gross and
      microscopic autopsy findings with procedural and ancillary studies, and review of
      the literature will help investigators and pathologists in the diagnosis of
      amniotic fluid embolism.

PMID- 15725784
TI  - A singular case of murder-suicide committed with a homemade firearm.
AB  - The authors illustrate a peculiar case of murder-suicide committed with a
      homemade firearm loaded with 12-gauge cartridges (buckshot). The structure and
      function of this handcrafted firearm were simple but effective: an iron tube did
      duty as a barrel in this primitive firearm. The cartridges (modified by winding
      sticky tape around the external surface of the base) were inserted down one end
      of the tube (serving as the breech). A second iron tube with a larger diameter
      (so as to be able to run over each of the preloaded barrels) and with a jutting,
      cone-shaped metal wedge soldered to the base, was used as a rudimental firing
      pin. After loading the "barrel" with the modified cartridge, the gunman would ram
      the "firing pin" tube violently down to fire the shot. Autopsy of the woman's
      body showed the presence of 3 gunshot wounds caused by buckshot, while the man
      had a single buckshot wound in the head. Subsequent ballistic investigations
      enabled reconstruction of the event (typical of murder-suicide) and the
      functioning of the firearm, demonstrating its lethal nature, remarkably easy
      handling, and simplicity of production.

PMID- 15725786
TI  - High urine ethanol and negative blood and vitreous ethanol in a diabetic woman: a
      case report, retrospective case survey, and review of the literature.
AB  - Several studies have shown that ethanol can be produced in urine infected with
      yeast or bacteria in vitro. We present the unusual case of a diabetic woman in
      whom ethanol was produced in her urine in vivo. The decedent was a 19-year-old
      woman who was noncompliant with her diabetes treatment. She presented to a local
      hospital in severe diabetic ketoacidosis and died shortly thereafter. Upon
      arrival at the hospital, a blood glucose of 553 mg/dL was detected. A urinalysis
      was positive for ketones (> 80 mg/dL), glucose (> 1000 mg/dL), and large budding
      yeast forms. A drug screen performed on the urine was positive for ethanol. At
      the coroner/medical examiner office, an autopsy was negative for significant
      anatomic findings. Toxicology analysis revealed a urine ethanol level 0.32 g/dL,
      although no ethanol was detected in blood or vitreous samples. A urine gram stain
      and culture identified Candida glabrata. A retrospective case review of all
      deaths related to diabetes examined at the coroner/medical examiner office from
      1986 to 2003 did not reveal other cases with similar findings. This case of a
      noncompliant, juvenile-diabetic woman illustrates a rare finding of apparent in
      vivo glucose fermentation by C. glabrata to form ethanol in the urine. This case
      also highlights a potential difficulty in toxicologic analysis and interpretation
      using urine only.

PMID- 15725787
TI  - Postacute care services use for dysvascular amputees: a population-based study of
      Massachusetts.
AB  - OBJECTIVE: Rehabilitation and other postacute care services utilization for
      persons with a lower limb amputations due to dysvascular disease is important
      information for physiatrists, therapists, patients, and health-policy planners.
      The purpose of this study was to examine rates of inpatient rehabilitation
      services use in a statewide population. DESIGN: Massachusetts Hospital Case Mix
      and Charge Data for 1997 were used to select persons with dysvascular limb
      amputations. Disposition locations after amputation were analyzed. RESULTS: There
      were 2487 persons who incurred a lower limb amputation, with the majority being
      white (94%), male (58%), and elderly (69 yrs). Most had diabetes (62%) or
      peripheral vascular disease (51%). The most common disposition was home (33%),
      with 16% receiving inpatient rehabilitation after amputation. Persons with
      transtibial and transfemoral amputations were the most likely to receive
      inpatient rehabilitation, 28% and 19% respectively. CONCLUSIONS: Sixteen percent
      of dysvascular amputees received inpatient rehabilitation services. This was
      higher than the 1997 rate for Maryland (12%) and suggests geographic differences
      in services utilization. Prospective studies are necessary to examine outcomes
      for persons receiving rehabilitation services in different care settings to
      define the optimal rehabilitation venue for functional restoration. Development
      of more specific International Classification of Diseases, Ninth Revision
      Clinical Modification codes for dysvascular amputations would further research
      and public policy efforts.

PMID- 15725788
TI  - Long-term medical care utilization and costs among traumatic brain injury
      survivors.
AB  - OBJECTIVE: To examine billing patterns and predictors of healthcare utilization
      and costs associated with traumatic brain injury. DESIGN: Retrospective cohort
      study of healthcare billings for 63 survivors of traumatic brain injury, over a
      19-mo period, using a state-sponsored Medicaid program. The relationship of
      indicators of injury severity and disability to billings and payments was
      investigated. Mean age at time of injury was 33 yrs. Mean highest Glasgow Coma
      Scale rating immediately after brain injury was 8. RESULTS: A total of 795,635 US
      dollars was billed to Medicaid for 3,950 services and medications used. A total
      of 281,897 US dollars was paid for these billings out of the Medicaid account
      studied. Billings were used for statistical analyses, as they were considered the
      most stable indicator of cost. Motor deficits at discharge from inpatient
      rehabilitation (FIM motor score) showed inverse relationships to total billings
      (rho = -0.42, P < 0.001), subcategories of billings reflecting equipment and
      supplies (rho = -.26, P = 0.020), and outpatient billings (rho = -0.27, P =
      0.015). Change in FIM motor scores during inpatient rehabilitation was inversely
      associated with billings (rho = -0.40). Change in FIM motor scores provided
      unique information in predicting utilization after accounting for demographic
      characteristics and severity of injury. CONCLUSIONS: Motor disability and
      improvement during inpatient rehabilitation were significant predictors of
      billings after traumatic brain injury. Initial severity of brain injury was not a
      significant factor in utilization.

PMID- 15725789
TI  - Reliability and validity of a wheelchair collision test for screening behavioral
      assessment of unilateral neglect after stroke.
AB  - OBJECTIVE: To examine the reliability and validity of a new wheelchair collision
      test (WCT) for screening behavioral unilateral neglect in people with stroke.
      DESIGN: A total of 19 patients with left hemiplegia resulting from first-ever
      stroke (mean +/- SD, 61.9 +/- 25.8 days after onset) were examined with the WCT,
      whereby the patient was asked to propel a wheelchair to pass four round chairs
      arranged in two rows. Separate tests were done using two different distances
      between the chairs: 120 and 140 cm. The number of collisions with the chairs was
      recorded. The Catherine Bergego Scale was used to evaluate behavioral unilateral
      neglect. Because unilateral neglect has an unfavorable impact on rehabilitation,
      the FIMtrade mark instrument was used to determine the function of daily
      activities. RESULTS: Test-retest reliability ranged from 0.68 to 0.97 in
      different situations in the WCT. The rate of agreement tested by Kappa statistics
      between the WCT and Catherine Bergego Scale was higher when the distance between
      chairs was 120 cm than when the distance was 140 cm (0.68 vs. 0.58). Spearman's
      rank-correlation coefficient between the WCT and Catherine Bergego Scale was 0.72
      (P < 0.001) if the distance between the chairs was 120 cm and 0.75 (P < 0.001) if
      the distance was 140 cm. The WCT and Catherine Bergego Scale correlated well with
      the FIM instrument. Spearman's rank-correlation coefficient between the Catherine
      Bergego Scale and FIM total score was -0.70 (P < 0.001). CONCLUSION: The WCT is a
      simple screening test with high test-retest reliability and validity to evaluate
      behavioral unilateral neglect.

PMID- 15725790
TI  - Reliability and validity of a self-report FIM (FIM-SR) in persons with amputation
      or spinal cord injury and chronic pain.
AB  - OBJECTIVE: To evaluate the reliability and validity of a self-report FIM (FIM-SR)
      in two samples of adults with disabilities. DESIGN: Participants in a clinical
      trial of amitriptyline for pain (n = 84 with spinal cord injury [SCI], n = 38
      with amputation) provided responses to the study measures via telephone
      interview. Reliability was estimated using Cronbach's alpha and test-retest
      correlation coefficients, and validity was examined by comparing FIM-SR scores
      with the Craig Handicap Assessment and Reporting Technique (CHART) by comparing
      the CHART scores between the participants with SCI and amputation, and by
      comparing CHART scores between subjects with different levels of SCI. RESULTS: In
      the SCI sample, the FIM-SR demonstrated adequate reliability, and correlational
      analyses supported the validity of the FIM-SR motor scales. In addition, the FIM
      SR motor scales discriminated subjects with different diagnoses (SCI vs.
      amputation) and injury levels (paraplegia vs. tetraplegia). The psychometric
      properties of the entire FIM-SR in the amputation sample and of the FIM-SR
      cognitive scales in the SCI sample were difficult to determine due to a ceiling
      effect in which these scale scores were skewed toward the top end of the range.
      CONCLUSIONS: The FIM-SR motor scales and total FIM-SR score are reliable and
      valid measures of perceived functional independence in individuals with SCI.
      However, all of the FIM-SR scales in the amputation sample, and the FIM-SR
      cognitive scales in the SCI sample, seem to be less useful measures of
      functioning due to subjects reporting high levels of independence. The FIM-SR
      should be retested in amputation samples with more variable levels of
      functioning.

PMID- 15725792
TI  - Musculoskeletal aspects of pregnancy.
AB  - Sex-specific care of musculoskeletal impairments is an increasingly important
      topic in women's health. This is clinically relevant and of paramount importance
      as it pertains to diagnosis and treatment of musculoskeletal and peripheral
      neurologic disorders of pregnancy and the puerperium. It is estimated that
      virtually all women experience some degree of musculoskeletal discomfort during
      pregnancy, and 25% have at least temporarily disabling symptoms. This review
      provides information on common pregnancy-related musculoskeletal conditions,
      including a discussion of anatomy and physiology, diagnosis, prognosis, and
      treatment of these disorders.

PMID- 15725793
TI  - Paraplegia secondary to progressive necrotic myelopathy in a patient with an
      implanted morphine pump.
AB  - We present an individual with chronic low back pain who was treated with an
      implanted morphine pump, which provided very good pain relief for 16 mos.
      However, the patient developed acute paraplegia secondary to progressive necrotic
      myelopathy, a rare form of transverse myelitis. The cause of this patient's
      neurologic deficit was unclear. Three months after the onset of paralysis, a
      trial of discontinuation of the intrathecal morphine was performed to exclude the
      morphine as a reversible cause of paralysis. Within 24 hrs after his pump was
      depleted, his pain became significantly worse. He was maintained on oral opioids
      for 6 mos, and his pain was only partly controlled, with a daily average visual
      analog scale score of 7/10. There was no improvement in his neurologic status
      after stopping the intrathecal morphine therapy, and several consecutive magnetic
      resonance images of the spine demonstrated radiologic progression of spinal cord
      involvement. The patient developed classic opioid side effects of excessive
      somnolence and constipation. Intrathecal morphine therapy was re-instituted, and
      the patient reported a significant decrease of his pain, an improvement in
      quality of life, and no complications related to pump functioning.

PMID- 15725794
TI  - Frontal contusions imaging and behavioral consequences.

PMID- 15725796
TI  - Synchronous and metachronous endocervical and ovarian neoplasms: evidence
      supporting interpretation of the ovarian neoplasms as metastatic endocervical
      adenocarcinomas simulating primary ovarian surface epithelial neoplasms.
AB  - The vast majority of endocervical adenocarcinomas are high-risk human
      papillomavirus (HPV)-related neoplasms, characterized by p16 expression and
      frequent loss of hormone receptor expression, which infrequently metastasize to
      the ovaries. We report 10 cases of endocervical adenocarcinomas with ovarian
      metastases in which the ovarian tumors simulated primary ovarian surface
      epithelial neoplasms. The presence of HPV DNA was assessed to determine whether
      the ovarian neoplasms were metastases or independent neoplasms.
      Immunohistochemistry for hormone receptors and p16 was also performed. The
      ovarian metastases presented concurrently with the primary endocervical tumors in
      5 cases, subsequent to the endocervical tumors in 3 cases, and prior to diagnosis
      of the endocervical tumors in 2 cases. The ovarian tumors ranged in size from 2
      to 30 cm, with tumors in 7 cases measuring 10 cm or greater. The ovarian tumors
      were unilateral in 8 cases and bilateral in 2. In all cases, the ovarian tumors
      were initially diagnosed as or thought to represent independent primary ovarian
      surface epithelial tumors (atypical proliferative [borderline] tumors or well
      differentiated carcinomas of endometrioid or mucinous type). The endocervical
      tumors ranged in size from microscopic foci to 3 cm, with depth of invasion
      ranging from 0.2 to 1.5 cm; in 2 cases, the invasive foci qualified as
      microinvasive according to Federation Internationale de Gynecologie et
      d'Obstetrique staging criteria for cervical carcinoma. Adenocarcinoma in situ was
      identified in all tumors. In all cases, the paired endocervical and ovarian
      tumors contained identical HPV types. All evaluable tumors were diffusely
      positive for p16; and in 8 cases, there was absent or only limited expression of
      hormone receptors. Two of the minimally invasive endocervical tumors were
      initially interpreted as adenocarcinoma in situ and not recognized as
      unequivocally invasive even when evaluated in conjunction with the histologically
      identical ovarian tumors. HPV DNA detection in the ovarian tumors of 2 patients
      without known cervical disease led to discovery of occult cervical
      adenocarcinomas in those patients. Endocervical adenocarcinomas, including some
      qualifying as microinvasive, can metastasize to the ovaries and simulate primary
      ovarian surface epithelial neoplasms. The presence of HPV DNA in these ovarian
      tumors confirms that they are metastatic endocervical adenocarcinomas.

PMID- 15725797
TI  - Description of a novel system for grading of endometrial carcinoma and comparison
      with existing grading systems.
AB  - The most widely used system for grading of endometrial carcinoma is the
      International Federation of Gynecology and Obstetrics (FIGO) grading system. This
      grading system requires evaluation of histologic features that are difficult to
      assess reproducibly. Two hundred and two cases of endometrial carcinoma, treated
      by hysterectomy, were retrieved from the archives of Vancouver General Hospital
      (1983-1998). For each tumor, the architectural pattern, nuclear grade, and
      mitotic index were assessed. The tumor architectural pattern, nuclear grade, and
      mitotic index were significant predictors of patient outcome (P < 0.0001 for
      each, by univariate analysis). There were no prognostic differences between
      patients having predominantly solid versus papillary tumors, or tumors with mild
      versus moderate nuclear atypia. The tumors were then classified into high and low
      grade based on assessment of these three features. The presence of at least two
      criteria of these three: 1) predominantly papillary or solid growth pattern, 2)
      mitotic index > or =6/10 high power fields, or 3) severe nuclear atypia, resulted
      in a tumor being considered high grade. Low-grade tumors satisfied at most one of
      those criteria. The proposed grading system was found to be an independent
      predictor of patient outcome when patient survival was adjusted for FIGO stage,
      patient age, and tumor cell type. It also had more prognostic power than other
      grading systems tested when it was applied to all tumors, regardless of their
      cell type; however, the FIGO grading system was superior for prognostication when
      only carcinomas of endometrioid type were considered. With the FIGO grading
      system, no significant difference in survival was observed between patients with
      grade 1 and grade 2 tumors. Combining FIGO grades 1 and 2 results in a binary
      system (grades 1 and 2 vs. grade 3) that was the most prognostically significant
      grading system tested, with the additional advantages of being highly
      reproducible and familiar to practicing pathologists.

PMID- 15725799
TI  - The histologic pattern of "biliary tract pathology" is accurate for the diagnosis
      of biliary complications.
AB  - A histologic pattern comprising centrilobular cholestasis and portal changes
      including edema, predominantly neutrophil polymorph infiltration, cholangiolar
      proliferation, and cholangiolitis is well known to correspond to biliary
      obstruction. This pattern, referred as biliary tract pathology (BTP) in this
      text, remains unclear in terms of its clinical significance. We aimed to assess
      the incidence, timing, and diagnostic accuracy of BTP after liver
      transplantation. All 248 liver biopsies and clinical records, from 94 patients,
      including 30 living donor, 17 split, 15 domino, and 32 cadaveric full-size
      primary liver transplantation, were reviewed. BTP was diagnosed in 21% of
      biopsies from 31% of patients at a median of 28 days after transplantation
      (range, 5-763 days). When radiologic imaging of the biliary tree was taken as the
      gold standard, biopsy was found to have a sensitivity of 87% (95% confidence
      interval, 73%-100%) and a specificity of 87% (95% confidence interval, 80%-95%)
      for the diagnosis of biliary complications. An underlying clinical condition was
      found in 86% of cases, which included biliary complications (69%), arterial
      thrombosis (3%), sepsis (10%), and recurrent disease (3%). In 14% of cases, BTP
      remained unexplained. In conclusion, BTP after liver transplantation has clinical
      significance in most cases, with a particular emphasis for true biliary
      complications. This pattern must incite radiographic verification of the biliary
      tract.

PMID- 15725798
TI  - Characterization of micrometastatic disease in melanoma sentinel lymph nodes by
      enhanced pathology: recommendations for standardizing pathologic analysis.
AB  - Lymphatic mapping and sentinel lymph node (SLN) biopsy are widely used as a
      staging technique for patients with cutaneous malignant melanoma who are at risk
      for metastases. SLN status has been shown to be a strong predictor of prognosis,
      and a variety of techniques have been used to identify minimal metastatic disease
      in SLNs. However, there is no validated consensus method for the optimal
      histologic analysis of SLNs harvested from melanoma patients. This study was
      conducted: 1) to assess the yield of metastatic melanoma detected in SLNs deemed
      negative by initial routine pathologic analysis (RPA) by subjecting them (after
      review of the original slides) to enhanced pathologic analysis (EPA) that
      included complete step-sectioning and immunohistochemistry (IHC); 2) to
      characterize the distribution of metastatic melanoma deposits within the SLNs; 3)
      to determine a preferred method of pathologic analysis applicable to daily
      practice; and 4) to attempt to assess the clinical significance of disease
      detected by EPA. A total of 105 SLNs were harvested from 49 patients who
      underwent successful SLN biopsy procedures during the period of study. Ten SLNs
      from 10 patients were positive on initial RPA and were not analyzed further.
      Ninety-five SLNs from the remaining 39 patients were reviewed and processed with
      additional hematoxylin and eosin, S-100 protein, and HMB-45 stains at 50-microm
      intervals for 20 levels or until the SLN tissue was exhausted. A single
      pathologist reviewed all sections without knowledge of the results of the other
      stains. Overall, metastatic melanoma was discovered in SLNs from 20 of the 39
      patients: SLNs from 6 patients were found to have melanoma on review of the
      original hematoxylin and eosin slides, and SLNs from 14 patients were positive
      only after EPA. Twenty-one individual positive SLNs from these 14 patients were
      detected by EPA; of these, 10 positive SLNs were identified solely by IHC,
      representing 12% of the patient cohort and 10% of all SLNs studied by EPA.
      Detection rates were significantly associated with the staining method and the
      number of levels performed (P < 0.01). S-100 protein staining resulted in the
      highest yield of SLN positivity (86%), followed by HMB-45 (81%) and hematoxylin
      and eosin (52%). No single method detected all of the micrometastases. A detailed
      topographic mapping of metastatic deposits in SLNs was carried out. When using
      all three staining techniques, all 20 levels were required to identify 100% of
      the micrometastases; 95% of positive SLNs were identified with 17 levels, 90%
      with 15 levels, 75% with 10 levels, and 42% with 3 levels. Projected rates of
      detection for various different sectioning strategies were determined, with
      alteration of either the number of levels examined, the interval between the
      levels, or both. Detection of SLN positivity can be increased to 71% by
      performing three levels at 250-mum intervals, each level being composed of a set
      of three sections stained with hematoxylin and eosin, S-100 protein, and HMB-45,
      respectively. Therefore, this is the methodology we propose for the study of SLNs
      in melanoma patients. After a median follow-up of 87 months (range, 9-134
      months), patients with EPA-detected disease and those with negative SLNs by EPA
      demonstrated improved recurrence-free and disease-specific survival compared with
      patients with RPA-detected disease in SLNs. Sampling error introduced by
      variations in pathologic processing should be addressed by standardization of
      pathologic methods, and the clinical significance of minimal SLN disease should
      be addressed in prospective studies of homogeneously staged patients.

PMID- 15725800
TI  - Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors
      of the lung.
AB  - Few data on the influence of vessel invasion on the progression of neuroendocrine
      lung tumors are available. Because of the lack of specific markers, previous
      studies could not reliably discriminate lymphatic and blood vessels. By
      immunostaining for podoplanin, specific for lymphatic endothelium, and CD34
      antigen, we assessed lymphatic and blood vessel invasion in 120 tissue specimens
      of patients with neuroendocrine lung tumors. Lymphovascular invasion was
      correlated with clinicopathologic parameters, and its prognostic relevance was
      evaluated. Lymphatic vessels were identified exclusively at the tumor invasion
      front, whereas blood capillaries were also seen within tumors. Lymphatic vessel
      as well as lymphatic and blood vessel invasion was prevalent in patients with
      high-grade neuroendocrine tumors and advanced tumor stages, closely associated
      with lymph node metastases (P < 0.0001). In univariate analysis, these two
      invasion types correlated with decreased disease-free survival (both P < 0.0001),
      whereas blood vessel invasion alone did not. In multivariate analysis, only tumor
      grade and lymph node status remained statistically significant factors for
      prognosis (P = 0.016 and P < 0.0001). Our results suggest that evaluation of
      lymphatic vessel invasion is important in neuroendocrine lung tumors serving as a
      prognostic parameter for disease-free survival.

PMID- 15725801
TI  - Immunopathology of primary hypophysitis: implications for pathogenesis.
AB  - The etiology of primary hypophysitis is still not fully elucidated.
      Histologically, primary hypophysitis includes three different main subtypes:
      lymphocytic (LYH), granulomatous (GRH), and xanthomatous (XH) hypophysitis.
      Clinical and laboratory findings suggest an autoimmune basis in primary
      hypophysitis. Controversy still exists about the composition of the inflammatory
      infiltrate and the relevant immunopathogenic effector mechanisms. Therefore, 21
      cases of primary hypophysitis of different subtypes were analyzed with respect to
      the expression of lymphocyte and macrophage antigens as well as MHC class I and
      II molecules of the inflammatory infiltrate and the resident pituitary acinar
      cells. Lymphocyte infiltration in LYH (n = 15), but also in GRH (n = 4) and XH (n
      = 2), mainly consisted of T cells, while B cells were rare. Independent from the
      histopathologic subtype, T cell subsets showed equal ratios of CD4+ to CD8+ T
      cells. Highest numbers of activated CD8+ T cells were observed in LYH presenting
      during pregnancy, surrounding or even infiltrating preserved pituitary acinar
      cells. Moreover, an increased rate of activated CD8+ T cells correlated with a
      shorter duration of clinical symptoms. In LYH, aberrant expression of MHC class
      II antigens as well as overexpression of MHC class I molecules on pituitary cells
      were observed. Independent of the histologic subtype, macrophages mostly
      expressed markers of chronic activation and showed MHC class II positivity. LYH,
      GRH, and XH, although heterogeneous in their histologic appearance and in age
      distribution, exhibit a similar if not identical immunohistologic profile. It is
      highly likely that direct T cell-mediated cytotoxicity through CD8+ T cells, with
      the initial help of CD4+ T cells, is pivotal in the pathogenesis of primary
      hypophysitis, implicating a target autoantigen expressed by pituitary cells.

PMID- 15725802
TI  - Primary intrathoracic synovial sarcoma: a clinicopathologic study of 40 t(X;18)
      positive cases from the French Sarcoma Group and the Mesopath Group.
AB  - Synovial sarcoma (SS), an aggressive neoplasm accounting for up to 14% of soft
      tissue sarcomas, was recently recognized as a primary tumor in the lung and
      pleura. SS is characterized by the chromosomal translocation t(X;18)(SYT-SSX)
      found in more than 95% of the tumors. We report a cooperative study from the
      French Sarcoma Group and the Mesopath Group on 40 t(X;18)(SYT-SSX)-positive
      primary intrathoracic SS. There were 22 males and 18 females, whose age ranged
      from 16 to 79 years (median, 47 years). Neoplasms were mostly circumscribed and
      of large size (median, 7.5 cm; range, 2-16 cm). Thirty-nine tumors were
      monophasic SS, including 24 (60%) monophasic fibrous and 15 (37.5%) poorly
      differentiated cases, and one lesion was a biphasic SS. A larger proportion of
      poorly differentiated tumors were observed among intrathoracic SS as compared
      with soft tissue SS. Immunohistochemically, 90% of the cases reacted with at
      least one epithelial marker. CD34 was focally expressed in 3 cases. SYT-SSX1
      fusion transcripts were detected in 22 cases (56.4%) and SYT-SSX2 fusion
      transcripts in 17 cases. Median and 5-year disease-specific survival in 33
      patients was 50 months and 31.6%. Median and 5-year disease-free survival was 24
      months and 20.9%. Patient sex, age, tumor size, histologic subtype, grade, and
      SYS-SSX fusion type had no significant impact on outcome. In conclusion,
      intrathoracic SS are rare but aggressive tumors with poor prognosis. In this
      unusual location, the detection of SYT-SSX fusion transcripts is a valuable
      diagnostic adjunct.

PMID- 15725803
TI  - Metaplastic breast carcinomas: are they of myoepithelial differentiation?:
      immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial
      markers.
AB  - We investigated 20 spindle cell (sarcomatoid) metaplastic carcinomas (MCs)
      without squamous differentiation. In addition, five high-grade phyllodes tumors
      were assessed for comparison. Our immunohistochemical antibody panel included pan
      cytokeratin (CK), low molecular weight CK (CK8/18), four basal cell type CKs
      (34betaE12, CK5/6, CK14, and CK17), vimentin antibodies, as well as antibodies to
      established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel
      (CD29, 14-3-3sigma) myoepithelial markers. Sixteen of the 20 tumors (80%)
      expressed at least two markers of the combination CD10/p63/SMA. S-100 detected 1
      case negative for CD10/p63/SMA and 3 cases that only expressed one marker of this
      combination. While 18 MCs (90%) were positive for CD29, 14-3-3sigma (11 cases)
      and maspin (9 cases) were observed in 55% and 45%, respectively. Antibodies to
      pan-CK and the basal cell type CKs were strongly reactive in 12 tumors (60%), but
      in 6 cases (30%) positivity for these markers was weak and only focal; 2 MCs
      showed no positivity for CK. The stromal component of all phyllodes tumors was
      positive for vimentin, whereas all other investigated markers were absent except
      for focal p63 and CD10 expression in 1 case each. Our findings convincingly show
      a myoepithelial immunophenotype in sarcomatoid MCs, which is demonstrated by the
      presence of basal cell type CKs and the combination of the established
      myoepithelial markers CD10, p63, SMA, and S-100. We conclude that tumors with
      weak or even absent CK expression should only be diagnosed as primary sarcomas of
      the breast after exclusion of a myoepithelial immunophenotype. CD29 and 14-3
      3sigma represent valuable novel myoepithelial markers in these diagnostically
      difficult cases.

PMID- 15725804
TI  - Pathologic features of breast cancer associated with complete response to
      neoadjuvant chemotherapy: importance of tumor necrosis.
AB  - Breast cancer patients with a complete pathologic response after neoadjuvant
      chemotherapy have a better prognosis than incomplete responders. The predictive
      value of the histologic characteristics of the tumor prior to neoadjuvant
      treatment has not been well defined, and there are no guidelines for reporting
      tumor characteristics in the core biopsy report. Histologic and nuclear grades,
      presence of tumor necrosis and angiolymphatic invasion (ALI), and estrogen
      receptor (ER), progesterone receptor (PR), and HER-2/neu expression were assessed
      in core biopsies of 55 patients with invasive carcinomas. Patients were then
      uniformly treated with four cycles of doxorubicin/docetaxel followed by excisions
      and lymph node dissections. Complete pathologic response (pCR) was defined as
      having no invasive carcinoma at excision. Noncomplete pathologic response was
      defined as having invasive carcinoma at excision. Five of the 55 patients (9%)
      achieved pCR. Of the 5 complete responders, 4 (80%) had tumor necrosis in the
      core biopsy specimens, while only 8 of the 46 (17%) noncomplete responders (pNR)
      had this feature (P = 0.0086). Higher histologic and nuclear grades, ER, PR
      status, and HER-2/neu overexpression were not associated with pCR. The presence
      of ALI in the core biopsy, post-therapy excision, or both was associated with
      axillary lymph node metastases (P = 0.0062, P = 0.0249, and P = 0.0021,
      respectively). Although preliminary, our study suggests that the presence of
      tumor necrosis and ALI in the core biopsy may be important features to be
      included in the standard report.

PMID- 15725805
TI  - Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of
      Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2.
AB  - Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to
      regional lymph nodes, liver, or lung and are difficult to diagnose because they
      lack specific immunohistochemical markers. We studied the expression of
      cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1
      (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal
      carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic
      cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic
      ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary
      carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively),
      and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively).
      More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse
      cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra
      pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them
      showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to
      the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal
      papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely
      expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the
      ampullary carcinoma of pancreatobiliary origin and in intrahepatic
      cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6
      cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24
      intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal
      carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet
      ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous
      CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating
      pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous
      adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic
      organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and
      malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for
      pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin,
      and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%,
      respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type
      adenocarcinoma of duodenal papillary origin with a positive predictive value of
      82%.

PMID- 15725806
TI  - OCT4 immunohistochemistry is superior to placental alkaline phosphatase (PLAP) in
      the diagnosis of central nervous system germinoma.
AB  - OCT4 is an 18-kDa POU-domain transcription factor encoded by the POU5F1 gene.
      Also known as OCT3, OTF3, and POU5F1, OCT4 is involved in the initiation,
      maintenance, and differentiation of pluripotent and germline cells during normal
      development. It is expressed in mouse and human embryonic stem and germ cells but
      absent from all differentiated somatic cell types in vitro and in vivo. OCT4 has
      been detected in primary testicular germ cell tumors with pluripotent potential:
      seminoma and embryonal carcinoma. We investigated: 1) whether a similar pattern
      of expression is present in primary intracranial germinomas; and 2) how OCT4
      compares with placental alkaline phosphatase (PLAP) in terms of specificity and
      sensitivity as a potential diagnostic tool. We examined histologic sections from
      25 cases of germinoma in which paraffin blocks with sufficient material were
      available. All cases were reviewed and sections from 32 different blocks were
      obtained and immunostained for OCT4 and PLAP. Additionally, 49 primary and
      metastatic brain tumors that may be potentially confused with germinoma, either
      clinically or histologically, were investigated for OCT4 expression. All but one
      germinoma were pure (ie, lacking other germ cell components). Intense and often
      diffuse nuclear staining was detected in 100% of germinomas. PLAP
      immunoreactivity was detected in 23 of 25 cases and was absent in the remaining 2
      cases. The intensity of OCT4 immunostaining was significantly better than that of
      PLAP. None of the 49 control cases, which included glioblastoma multiforme,
      pineoblastoma, pituitary adenoma, malignant lymphoma, metastatic melanoma,
      capillary hemangioblastoma, meningioma, schwannoma, and a variety of metastatic
      carcinomas showed immunoreactivity for OCT4. Our study demonstrates that OCT4 is
      a highly specific and sensitive immunohistochemical marker for primary
      intracranial germinomas. OCT4 should be part of immunoperoxidase staining panels
      in which germinoma enters the differential diagnosis.

PMID- 15725807
TI  - Biologic properties of columnar epithelium underneath reepithelialized squamous
      mucosa in Barrett's esophagus.
AB  - Chronic proton pump inhibitor (PPI) therapy may lead to partial regression of
      Barrett's esophagus (BE), resulting in the development of reepithelialized
      islands of squamous mucosa that may cover the underlying BE. The purpose of this
      study was to evaluate the clinical, histologic, and biologic characteristics of
      BE that is situated underneath squamous islands (BUSI). A total of 97 mucosal
      biopsies from 44 BE patients with BUSI were evaluated for a variety of histologic
      features (eg, type of epithelium, anatomic relationship of the underlying glands
      to the luminal surface, presence of adjacent mucosal glands or ducts, and the
      presence and degree of dysplasia), and immunostained for Ki-67, cyclin D1, and
      p53. BUSI was compared with adjacent areas of BE for all parameters. A clinical
      control group consisting of 50 BE patients without microscopic evidence of BUSI
      was selected for comparison of clinical and endoscopic features. The study group
      (34 males, 10 females; mean age, 67 years; mean length of BE, 5.5 cm) consisted
      of 27 (61%) and 12 (27%) patients on low- and high-dose PPI, respectively. On
      endoscopy, visible islands of squamous mucosa were noted in only 43% of study
      group patients (despite the presence of BUSI microscopically in all cases); one
      island was noted in 2%, multiple islands in 27%, and extensive islands in 14% of
      patients. The extent of squamous islands was unrelated to PPI dose. The study
      group was significantly more likely to have endoscopic evidence of extensive
      squamous islands compared with the control group (P = 0.009). Histologically, 89%
      of biopsies with BUSI showed intestinal-type, and 11% showed cardia-type,
      epithelium. Low- and high-grade dysplasia was noted in 4 (4%) and 5 (5%)
      biopsies, respectively. All patients with dysplasia in BUSI also showed dysplasia
      in other areas of the esophagus as well. Interestingly, BUSI reached the mucosal
      surface either by penetrating directly through, or by wrapping around, islands of
      squamous epithelium, in 68% of biopsies. Twenty-one percent of biopsies showed
      BUSI adjacent to submucosal glands or ducts. BUSI showed a significantly lower Ki
      67 proliferation rate (29% vs. 49%, P < 0.001), and a lower, albeit
      nonsignificant, degree of cyclin D1 (16% vs. 29%) and p53 (4% vs. 17%) positivity
      in comparison to adjacent areas of BE. Furthermore, significantly lower
      proliferation rates were observed in BUSI that did not reveal an opening to the
      mucosal surface in comparison to foci that did. BUSI is phenotypically similar to
      typical surface BE but shows less severe proliferative abnormalities,
      particularly in buried glands that have no detectable connection to the
      esophageal lumen. Reduced proliferation may be due either to decreased exposure
      to luminal contents or to disruption of sloughing of surface epithelial cells
      into the crypt lumen. Prospective studies of large numbers of patients with BUSI
      will be required to determine the magnitude of its risk of progression to cancer.

PMID- 15725808
TI  - Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas
      from bile duct adenomas and hamartomas of the liver.
AB  - Not uncommonly, bile duct adenomas (BDAs) and hamartomas (BDHs) of the liver may
      be difficult to distinguish from metastatic well-differentiated ductal
      adenocarcinoma of the pancreas. However, this distinction is critical for proper
      staging and patient management. The primary purpose of this study was to
      determine if a panel of immunohistochemical stains can help distinguish BDA or
      BDH from metastatic pancreatic adenocarcinoma in the liver. Routinely processed
      tissue sections from 25 BDA, 10 BDH, 25 metastatic pancreatic adenocarcinomas to
      the liver and 6 cases each of metastatic colorectal, breast, and lung
      adenocarcinomas were immunohistochemically stained for CK7, CK8/CK18, CK19, CK20,
      p53, p63, TAG-72, monoclonal CEA (mCEA), polyclonal CEA (pCEA), HER-2/neu, AMACR
      (alpha-methylacyl-CoA racemase), Dpc4 (Smad4), and mesothelin. The slides were
      evaluated in a blinded fashion, and the results were compared between the benign
      and malignant lesions. Significantly more (P < 0.05) metastatic pancreatic
      adenocarcinomas were positive for CK20 (76%), p53 (60%), TAG-72 (88%), mCEA
      (92%), HER2/neu (40%), and mesothelin (64%) and showed loss of Dpc4 (44%), in
      comparison to BDA (CK20, 40%; p53, 0%; TAG-72, 0%; mCEA, 0%; HER2/neu, 12%;
      mesothelin, 0%; loss of Dpc4, 0%) or BDH (CK20, 10%; p53, 0%; TAG-72, 0%; mCEA,
      10%; HER2/neu, 0%; mesothelin, 0%; loss of Dpc4, 0%). Of these antibodies, p53,
      TAG-72, mCEA, loss of Dpc4, and mesothelin had the highest specificity for
      pancreatic adenocarcinoma, with mCEA having the highest sensitivity (92%). No
      significant differences were observed in the degree of CK7, CK8/CK18, CK19, or
      pCEA expression between the three types of lesions. Although none of the BDA or
      BDH was positive for either p63 or AMACR, two of the metastatic pancreatic
      adenocarcinomas (8%) were positive for each of these peptides (P > 0.05). For
      nonpancreatic adenocarcinomas, mCEA showed a reasonably high sensitivity and 100%
      specificity in the differential diagnosis versus BDA. Immunohistochemical
      expression of p53, TAG-72, mCEA, mesothelin, and loss of Dpc4 can help
      distinguish metastatic pancreatic adenocarcinoma in the liver from BDA or BDH.
      Although p63 and AMACR are also specific for pancreatic adenocarcinoma, their low
      sensitivity limits their use in clinical practice.

PMID- 15725809
TI  - CDC2/CDK1 expression in esophageal adenocarcinoma and precursor lesions serves as
      a diagnostic and cancer progression marker and potential novel drug target.
AB  - Esophageal adenocarcinoma arises through well-defined precursor lesions (Barrett
      esophagus), although only a subset of these lesions advances to invasive
      adenocarcinoma. The lack of markers predicting progression in Barrett esophagus,
      typical presentation at advanced stage, and limitations of conventional
      chemotherapy result in >90% mortality for Barrett-associated adenocarcinomas. To
      identify potential prognostic markers and therapeutic targets, we compared gene
      expression profiles from Barrett-associated esophageal adenocarcinoma cell lines
      (BIC1, SEG1, KYAE, OE33) and normal esophageal epithelial scrapings utilizing the
      Affymetrix U133_A gene expression platform. We identified 560 transcripts with >3
      fold up-regulation in the adenocarcinoma cell lines compared with normal
      epithelium. Utilizing tissue microarrays composed of normal esophageal squamous
      mucosa (n = 20), Barrett esophagus (n = 10), low-grade dysplasia (n = 14), high
      grade dysplasia (n = 27), adenocarcinoma (n = 59), and node metastases (n = 27),
      we confirmed differential up-regulation of three proteins (Cdc2/Cdk1, Cdc5, and
      Igfbp3) in adenocarcinomas and Barrett lesions. Protein expression mirrored
      histologic progression; thus, 87% of low-grade dysplasias had at least focal
      surface Cdc2/Cdk1 and 20% had >5% surface staining; 96% of high-grade dysplasias
      expressed abundant surface Cdc2/Cdk1, while invasive adenocarcinoma and
      metastases demonstrated ubiquitous expression. Esophageal adenocarcinoma cell
      lines treated with the novel CDC2/CDK1 transcriptional inhibitor, tetra-O-methyl
      nordihydroguaiaretic acid (EM-1421, formerly named M4N) demonstrated a dose
      dependent reduction in cell proliferation, paralleling down-regulation of
      CDC2/CDK1 transcript and protein levels. These findings suggest a role for
      CDC2/CDK1 in esophageal adenocarcinogenesis, both as a potential histopathologic
      marker of dysplasia and a putative treatment target.

PMID- 15725810
TI  - Immunohistochemical analysis of novel monoclonal antibody PNL2 and comparison
      with other melanocyte differentiation markers.
AB  - PNL2 is a novel monoclonal antibody, which has recently been introduced as an
      immunohistochemical reagent to stain melanocyte and tumors derived thereof. In
      the present study, we analyzed the immunoreactivity of this mAb in various normal
      tissues, melanocytic nevi, primary and metastatic melanoma, nonmelanocytic
      tumors, including histologic mimickers of melanoma as well as angiomyolipoma, and
      multiple cell lines derived from different tumors types. We used several tissue
      microarray panels as well as selected conventional sections from tissue blocks.
      For metastatic melanoma, immunoreactivity for PNL2 was compared with A103 (Melan
      A/MART-1), T311 (tyrosinase), HMB45 (gp100), and D5 (MITF). Positive staining
      with PNL2 was found in normal melanocytes and neutrophils, but no other normal
      cell type. Among melanocytic lesions, both benign nevi as well as primary
      malignant melanomas, especially epithelioid variants thereof, were commonly
      immunopositive. Only 1 of 13 desmoplastic melanomas reacted with PNL2. PNL2
      showed high sensitivity for metastatic melanoma (87%). In comparison, 82% of
      metastatic melanomas were positive for A103, 76% for HMB45, 92% for T311, and 84%
      for D5. The combined use of all five reagents minimized the number of
      immunonegative cases. None of the selected nonmelanocytic tumors (carcinomas or
      soft tissue neoplasms) was positive for PNL2 in this series except for
      angiomyolipomas and chronic myeloid leukemias and 1 single case of a malignant
      peripheral nerve sheath tumor with heterologous differentiation (malignant Triton
      tumor). Despite its reactivity with neutrophils, PNL2 appears to be a valuable
      supplementary reagent for the diagnosis of melanocytic tumors.

PMID- 15725811
TI  - Pulmonary mucoepidermoid carcinoma with prominent tumor-associated lymphoid
      proliferation.
AB  - We report 6 cases of low-grade pulmonary mucoepidermoid carcinoma displaying a
      striking lymphoplasmacytic infiltrate. All six tumors had a typical pulmonary
      mucoepidermoid carcinoma presentation as a polypoid endobronchial mass involving
      the proximal bronchi. The patients were 3 females and 3 males with a mean age of
      33 years (range, 5-61 years). Half of the patients were asymptomatic, while half
      experienced mild symptoms of pneumonia, asthma-like symptoms, or hemoptysis. No
      tumor-related deaths were observed, with a mean follow-up of 51 months. The tumor
      size ranged from 2.1 to 3.4 cm (mean, 2.9 cm). The tumors characteristically
      displayed an elaborate tubulocystic epithelial component composed of
      intermediate, epidermoid, and mucus-producing cells, and variable numbers of
      clear cells, multinucleated giant cells, columnar cells, and oncocytic cells. The
      tumors' lymphoplasmacytic infiltrate with occasional Russell bodies was
      sufficiently intense to raise concern of a low-grade lymphoma. All tested tumors
      were immunoreactive with CK7 while nonreactive with TTF-1 and CK20. Recognition
      of this histologic variant is important for a correct diagnosis of low-grade
      pulmonary mucoepidermoid carcinoma. The dense lymphoplasmacytic infiltrate is
      similar to that previously described in salivary glands as tumor-associated
      lymphoid proliferation.

PMID- 15725812
TI  - Sentinel lymph node biopsies for cutaneous melanoma.

PMID- 15725813
TI  - Microthymoma: definition of the entity and distinction from nodular hyperplasia
      of the thymic epithelium (so-called microscopic thymoma).
AB  - We report 2 cases of microscopic-sized thymoma, which probably represents the
      earliest phase of thymoma development. The 2 patients presented with pure red
      cell aplasia and myasthenia gravis, respectively. The thymectomy specimens did
      not reveal tumor on gross examination, but histologically each contained small
      thymomas measuring 5 mm and 7 mm in largest dimension, respectively. One of the
      tumors was unencapsulated and involved a single lobule only, and the other was
      encapsulated and comprised two lobules. The tumors consisted of ovoid epithelial
      cells with pale nuclei and distinct nucleoli, scattered in a background of small
      lymphocytes. Foci of medullary differentiation and perivascular space were
      identified in the 2 cases, respectively. The lymphocytes were confirmed to be
      immature T cells on immunohistochemical studies (CD3+, TdT+). Except for the
      microscopic size, the morphology of the two tumors conforms to conventional type
      B1/B2 and type B2 thymoma, respectively. We propose calling such incidental small
      tumor "microthymoma" to distinguish it from the so-called microscopic thymoma,
      which is composed of small thymic epithelial nests and probably more
      appropriately termed "nodular hyperplasia" of the thymic epithelium.

PMID- 15725814
TI  - Mesodermal adenosarcoma of the testis.
AB  - Biphasic neoplasms with a benign to atypical epithelial component and a usually
      low-grade malignant stromal component have been reported in various sites,
      probably being best known for their occurrence in the uterine corpus (mullerian
      adenosarcoma). We report a tumor of this type that occurred in the testis of a 76
      year-old man and, to our knowledge, is the first mesodermal adenosarcoma reported
      at this site. The patient had scrotal swelling for many years with a pronounced
      increase in the swelling over the past 2 years. A large complex solid-cystic
      testicular tumor was evident on ultrasound, and examination of a radical
      orchiectomy specimen showed a 6.5-cm mass. On microscopic examination, the
      neoplasm had a phyllodes-like appearance with bland cuboidal to flattened
      epithelium covering polypoid fronds, and lining glands and cysts. The stroma
      varied from cellular, particularly where it condensed around the glands and
      cysts, to hypocellular and hyalinized. It was immunoreactive for muscle specific
      actin, CD10, and to a lesser degree, desmin. This case expands the known sites
      where mesodermal adenosarcoma may occur. The histogenesis is speculative, but
      possible options are discussed.

PMID- 15725816
TI  - Endocervical-like mucinous borderline tumors.

PMID- 15725818
TI  - The history of the Jurkiewicz society.

PMID- 15725819
TI  - Preliminary (3 years) experience with smooth wall silicone gel implants for
      primary breast augmentation.
AB  - The goal of this study is to obtain data concerning the incidence of capsular
      contracture and reoperation rates in patients having primary breast augmentation
      utilizing modern low-bleed smooth-wall silicone gel implants. Data were collected
      retrospectively and consisted of 44 patients who underwent primary breast
      augmentation using smooth silicone gel implants (Mentor Corporation) in the
      period between 2001 and 2003. Of the 131 patients identified, 44 patients fit the
      criteria of primary breast augmentation. Secondary cases and primary augmentation
      with mastopexy were excluded from this study. This group of patients is still
      followed, and the data are being updated periodically. A total of 44 patients
      underwent primary breast augmentation. Average age was 32 years (range, 19-57).
      Average follow-up was 34 months (range, 28-40). Average operative time was 52
      minutes. The inframammary incision was used in 65% of patients and the areolar
      incision in 35%. The subglandular position was used in 35% of patients versus the
      submuscular position in 65%. Nine patients (20%) developed capsular contracture.
      Six patients (13.6%) had Baker 3 capsular contracture, which required revision.
      Four of the 9 patients with capsular contracture had implants placed in the
      submuscular space and 5 in the subglandular position. Relative to the implant
      position, 4 patients (9%) with implants placed in the submuscular position
      developed capsular contracture. Relative to the subglandular position, 5 patients
      (11.3%) with implants placed in the subglandular position developed capsular
      contracture. Eight patients (19%) required implant revision, 6 patients for
      capsular contracture, and 2 patients requested size change. Preliminary data from
      this study indicate that the use of the new generation of gel implants yields
      less capsular contracture, as well as decreased revision rates. Subglandular
      placement of gel implants did not significantly increase the risk of capsular
      contracture. Longer follow-up and multicenter studies are still needed to confirm
      these findings. This cumulative data could challenge the current status of gel
      implant moratorium imposed by the incidence of capsular contracture and revision
      rates.

PMID- 15725821
TI  - A comparison of the LeJour and Wise pattern methods of breast reduction.
AB  - Supporters of the vertical mammoplasty state the resultant breast shape and scar
      are superior to the Wise pattern breast reduction. This study contains a
      comparison of the LeJour vertical reduction with the Wise pattern reduction by
      analysis of pre- and postoperative photographs, as well as a retrospective review
      comparing operative times, blood loss, complications, and a postoperative patient
      questionnaire. Of the 112 women who had moderate to large reductions (>500
      g/breast) between 1999 and 2002, 65 subjects had adequate standard perioperative
      photographs. Esthetic appearance, symmetry, nipple quality, and scarring were
      assessed using a Likert scale (10 = superior, 1 = poor) by 30 evaluators. Based
      on the photographic analysis, there is no difference in the esthetic outcome
      between the vertical reduction mammaplasty and the inferior pedicle Wise pattern
      mammaplasty. Additionally, this study indicates that vertical patients with
      moderate to large reductions have a significantly higher rate of complications
      when their body mass index is greater than 30 kg/m.

PMID- 15725823
TI  - Nipple reconstruction: the top hat technique.
AB  - A new surgical technique was evaluated in 23 nipple-areola complex
      reconstructions in 18 consecutive patients who underwent breast reconstruction
      techniques. The author used 2 rows of pursestring sutures, one at the base of the
      neonipple and the other at the periphery of the neoareola. The pursestring
      sutures act as a supporting platform. The nipple projection was created by
      suturing in a vertical fashion: 4 horizontal incisions creating 4 supporting
      pillars. The Montgomery tubercles were simulated by secondary healing of 2- or 3
      mm randomly placed stab incisions in the neoareola. The micropigmentation of the
      nipple-areola complex was performed preferably 6 weeks before the nipple-areola
      reconstructions. The mean follow-up time was 18 months. The average nipple
      projection was 6 mm, and the average diameter was 10 mm. Two patients presented
      with partial loss of nipple projection. Overall, more than 90% of the patients
      were satisfied with this procedure.

PMID- 15725824
TI  - Infonomics and breast reconstruction: are patients using the internet?
AB  - The World Wide Web provides access to an enormous amount of medical information.
      In particular, it enables the nonmedical community a chance to better understand
      breast reconstruction. The purpose of this survey is to determine patient access
      to the Internet for information related to their breast reconstruction and to
      evaluate the role of internet-based information in patient education. One hundred
      six consecutive breast reconstruction patients over a 7-month period were
      included in the study. All patients were given an anonymous survey querying
      patient demographics, education, type of reconstruction, internet usage, and how
      it affected their decision. Data were evaluated and comparisons were made. The
      average age was 50 years, with the majority of the reconstructions being pedicled
      TRAM flaps (50%). Ninety-two percent of the patients had internet access, most of
      them at home (71%). Sixty-eight percent of the patients reported having used the
      internet for information related to breast reconstruction. The categories
      searched were procedure (39%), risks/outcome (35%), surgeon (13%), pictures
      (11%), and hospital (4%). Seventy-two percent found it helpful, 69% easy to
      understand, and 63% trusted the information. The information they found
      influenced their decision regarding procedure (53% yes), surgeon (36% yes), and
      hospital (25% yes). Eighty-one percent felt that it would be useful to
      communicate with their surgeon via e-mail. Breast-reconstruction patients are
      using the internet as a research tool. They are influenced by this information on
      multiple levels. Infonomics is a growing field, and plastic surgeons must take an
      active role in guiding patients towards accurate online sources and becoming more
      accessible in the information superhighway.

PMID- 15725825
TI  - Secondary endoscopic forehead lift in patients with previous coronal brow lifts.
AB  - INTRODUCTION: The development of endoscopic surgical techniques has allowed an
      evolution from the standard coronal forehead lift to a minimally invasive one.
      Endoscopy avoids many of the undesirable results of the coronal approach while it
      remains very efficacious. The purpose of this study is to evaluate the
      effectiveness and safety of endoscopic forehead lift in patients who have
      previously undergone coronal brow lift. MATERIALS AND METHODS: A retrospective
      review was performed on the medical records of 726 consecutive patients who had
      undergone endoscopic forehead lift between 1994 and 2004. Sixty-three patients
      were identified who had undergone prior coronal incision brow lift and then
      required subsequent elevation of the forehead using endoscopy. Those who had
      persistent low eyebrows and forehead wrinkles underwent the standard minimal
      incision endoscopic approach. Patients with severe brow ptosis and excessive
      height of the forehead underwent a biplanar endoscopic forehead lift. RESULTS: Of
      the 63 endoscopic forehead lifts performed, 49 used the minimal access technique,
      while 14 employed the biplanar approach. The subject population consisted of 58
      female and 5 male patients whose average age was 57 years (range of 42 to 80
      years). Eighty-seven percent of these brow lifts also had concomitant
      rhytidectomy, and 4% had blepharoplasty. Average follow-up was 21 months (range 1
      to 7 years). Following the endoscopic procedure, none of the patients had frontal
      nerve injury, alopecia, or persistent glabellar wrinkle lines. Complications
      included 1 forehead dysesthesia, 1 forehead irregularity, 1 eyebrow malposition,
      1 persistent horizontal forehead wrinkling, and 2 hematomas. Operative management
      was not required for any of these complications. CONCLUSION: The secondary
      endoscopic forehead lift is effective in rejuvenating the upper face in the
      patient who has had a previous coronal forehead lift. It elevates the eyebrows
      and reduces both transverse and vertical wrinkles while avoiding further
      displacement of the hairline. The low rate of complications is comparable to that
      of primary endoscopic forehead lifts. Finally, serial follow-up indicates that
      the results are effective at correcting brow ptosis and are long lasting.

PMID- 15725826
TI  - Safety and efficacy of outpatient full abdominoplasty.
AB  - Full abdominoplasty (mobilization of skin flap to the costal margin/xiphoid,
      umbilical translocation, +/- liposuction) is frequently done as an inpatient
      procedure. This study evaluated the safety and efficacy of outpatient full
      abdominoplasty. Thirty-five full abdominoplasties were done: 17 inpatient, and 18
      outpatient. No significant outcome differences were noted between the 2 groups.
      Of the 17 inpatient procedures, 4 complications occurred (24%), 2 minor and 2
      major complications (large, open infected wounds). Of the 18 outpatient
      procedures, 2 minor complications (11%) occurred (urinary retention and wound
      infection). chi2 Analysis shows no statistical difference in the complications
      rates. All outpatients reported adequate postoperative pain and nausea control.
      All but 1 patient in each group was fully or very satisfied with the results.
      This study demonstrates the safety and efficacy of outpatient full
      abdominoplasty. Selection criteria and postoperative protocols will be discussed.

PMID- 15725827
TI  - Levator anguli oris: a cadaver study implicating its role in perioral
      rejuvenation.
AB  - The purpose of this study was to investigate the role of the levator anguli oris
      in perioral rejuvenation by delineating the detailed anatomy of this muscle and
      illustrating a new technique to elevate the oral commissure using this muscle.
      Fresh cadaver dissection was carried out in 9 facial halves specifically
      examining the anatomy of and surrounding the levator anguli oris. This muscle was
      identified in each cadaver to coalesce with the zygomaticus major muscle at the
      modiolus, thus elevating the oral commissure. In 3 facial halves, an intraoral
      incision from the canine to the modiolus was performed. This allowed easy access
      to the levator anguli oris muscle for plication and successful elevation of the
      oral commissure. This procedure could be applied in combination with traditional
      face lifts to enhance facial rejuvenation or potentially used to reanimate the
      partially paralyzed face.

PMID- 15725829
TI  - Comorbidity trends in patients requiring sternectomy and reconstruction.
AB  - INTRODUCTION: The predisposing risk factors for sternal wound infection have been
      well delineated. However, the indications and comorbidity of patients who require
      cardiac surgery via the median sternotomy approach have changed over time and
      subsequently have changed the patient population presenting with sternal wound
      complications. These trends in cardiac surgery may require an adjustment of the
      plastic surgical approach and methods to optimize outcomes in the patient
      population. METHODS: A retrospective review was performed to identify patients
      who had undergone sternectomy or sternal debridement followed by flap coverage. A
      total of 93 cases performed between 1999 and 2004 examined to collect data about
      the initial presentation, operative procedure, and postoperative care of each
      patient. The data were then analyzed to identify population characteristics using
      logistic regression variables to determine univariate and adjusted
      (multivariable) measures of association with mortality. RESULTS: Results of the
      review indicated that 53% of the patients were male and 47% were female, with a
      median age of 62 years. Preoperative comorbidities included 64% of the patients
      were over age 60, 43% had diabetes, 51% had hypertension, 13% had renal
      insufficiency, and 6% were transplant recipients. The method of reconstruction
      varied, but the majority were pectoralis advancement flaps. Of the patients who
      underwent debridement and reconstruction, there was a 16% 30-day mortality. Among
      these mortalities, the distribution was 33% (5/15) male and 66% (10/15) female.
      CONCLUSIONS: Though the incidence of sternal wound problems is rare (about 1%
      5%), there is a significant population of older, renal-insufficient, malnourished
      patients who present days or weeks after one would normally diagnose and treat a
      deep sternal wound infection who have a significant mortality rate. Appropriate
      identification of risk factors, preoperative management and timing for aggressive
      surgical treatment is required to maximize successful outcomes in this
      problematic patient population.

PMID- 15725831
TI  - Multidisciplinary approach to abdominal wall reconstruction after decompressive
      laparotomy for abdominal compartment syndrome.
AB  - INTRODUCTION: Decompressive laparotomy for abdominal compartment syndrome has
      been shown to reduce mortality in critically ill patients, but little is known
      about the outcome of abdominal wall reconstruction. This study investigates the
      role of plastic surgeons in the management and reconstruction of these abdominal
      wall defects. METHODS: We performed a retrospective review of 82 consecutive
      critically ill patients who underwent decompressive laparotomy for abdominal
      compartment syndrome, at a university level 1 trauma center, from April 2000 to
      May 2004. Patients reconstructed by trauma surgeons alone (n = 15) were compared
      with patients reconstructed jointly with plastic surgeons (n = 12), using Student
      t test and chi analysis. RESULTS: Eighty-two patients underwent decompressive
      laparotomy for abdominal compartment syndrome, yielding 50 survivors (61%). Of
      the 27 patients who underwent abdominal wall reconstruction, 6 had early primary
      fascial repair, and 21 had staged reconstruction with primary fascial closure (n
      = 4), components separation alone (n = 3), components separation with mesh (n =
      10), or permanent mesh only (n = 4). Compared with patients whose reconstruction
      was performed by trauma surgeons, patients who underwent a combined approach with
      plastic surgeons were older (50.5 versus 31.7 years, P < 0.05), had more
      comorbidities (P < 0.001), were less likely to have a traumatic etiology (P <
      0.001), had a longer delay to reconstruction (407 versus 119 days, P < 0.05), and
      were more likely to undergo components separation (P < 0.05). Mean follow-up of
      11.5 months revealed 2 recurrent hernias in the combined reconstruction group,
      both of which were successfully repaired. CONCLUSIONS: A multidisciplinary
      approach is essential to the successful management of abdominal wall defects
      after decompressive laparotomy for abdominal compartment syndrome. Although
      carefully selected patients can undergo early primary fascial repair, most of
      reconstructed patients had staged closure of the abdominal wall via components
      separation, with a low rate of recurrent hernia. High-risk patients with large
      defects and comorbidities appear to benefit from the involvement of a plastic
      surgeon.

PMID- 15725833
TI  - Reconstruction of limited soft-tissue defect with open tibial fracture in the
      distal third of the leg: a cost and outcome study.
AB  - This study was conducted to analyze the cost and outcome of free-tissue transfers
      versus local muscle flaps for reconstruction of limited soft-tissue defects
      associated with tibial fractures in the distal third of the leg. Twelve adult
      patients underwent either free (n = 6) or local muscle (n = 6) flap
      reconstruction were retrospectively reviewed. Total operative time for local
      muscle flap reconstruction was 215 +/- 47 minutes compared with 450 +/- 90
      minutes (P < 0.0002) for free-muscle transfer. Median length of hospital stay
      after reconstruction was 7 days for local muscle flap compared with 9 days for
      free-muscle transfer. Total cost of the local muscle flap procedure was US
      dollars 11,729 +/- US dollars 4460 compared with US dollars 19,989 +/- US dollars
      3295 (P < 0.0004) for free-flap reconstruction. Five of 6 patients in each group
      had excellent soft-tissue contours. Fracture healing was evident in all patients
      of each group. Thus, a local muscle flap for reconstruction of a limited distal
      tibial wound appears to be more cost-effective than free-tissue transfer because
      of equivocal outcomes achieved but at approximately half of the cost.

PMID- 15725834
TI  - STARplasty for reconstruction of the burned web space: introduction of an
      alternative technique for the correction of dorsal neosyndactyly.
AB  - INTRODUCTION: Significant hand burns frequently result in dorsal neosyndactyly,
      despite appropriate wound care, excision/grafting, and occupational therapy.
      Patients often develop limited abduction, tethered flexion/extension, intrinsic
      tightness, and inversion of the web space. We present a new technique for
      neosyndactyly release: the STARplasty (Syndactyly Treatment After Release), named
      after the appearance of the reconstructed web. METHODS: We performed a
      retrospective review of 25 patients who underwent 66 web space reconstructions by
      a single surgeon, from January 2002 to December 2003. The STARplasty was
      developed prior to the study period, with the following goals: to use local
      tissue, negate the need for a skin graft, and permit early range of motion.
      Combined with longitudinal, transverse, and oblique releases, STARplasty uses a
      single volar flap, harvested from each sidewall of both proximal phalanges, with
      30-degree corners. STARplasty simultaneously deepens and widens the web space
      while correcting the angle of inclination. RESULTS: Sixteen patients (mean age:
      34 years; range: 3-62 years) underwent a total of 33 STARplasties, an average of
      37 months after burn injury. Mean area resurfaced per web was 5.2 cm, which
      contrasts with the 33 non-STARplasty reconstructions, which were used to
      resurface a mean area of 19.4 cm (P < 0.05) and included 5-flap z-plasties (17),
      full-thickness skin graft (10), 2-flap z-plasties (3), and advancement flaps (3).
      No complications occurred in the STARplasty group, including infection, flap
      loss, dehiscence, nerve injury, or recurrent contracture. All patients had
      improved function (mean follow-up: 6.7 months; range: 1-18 months). CONCLUSIONS:
      STARplasty is a new, safe, and efficacious technique to correct dorsal
      neosyndactyly and reconstruct the web space after burn injury.

PMID- 15725835
TI  - The viability of fatty tissues within adipose aspirates after conventional
      liposuction: a comprehensive study.
AB  - This study was conducted to evaluate the viability of fatty tissues within
      adipose aspirates after conventional liposuction and to examine their potential
      role as a source of donor material for possible future autogenous fat grafting.
      Samples of adipose aspirates (group I, n = 8) were obtained from adult female
      patients who underwent a conventional liposuction of the abdomen. Samples of
      fresh fatty tissues obtained from adult female patients who underwent an
      abdominoplasty (group II, n = 8) were cut into small pieces and served as a
      control. All samples were spun at 50 x g for 10 minutes; fatty tissues were then
      collected from the middle layer after centrifugation for the following studies:
      trypan blue vital staining for viable fatty cell counts, glycerol-3-phophatase
      dehydrogenase (G3PDH) assay for functional evaluation of fatty tissues, and
      routine pathology for histology of fatty tissues. There was no significant
      difference of viable fatty cell counts in group I compared with group II (2.57 +/
      0.56 versus 2.74 +/- 0.59 x 10/mL, P = 0.56). G3PGH assay showed a marked
      decrease of the enzyme activity in group I compared with group II (0.34 +/- 0.13
      versus 0.76 +/- 0.13 micro/mL, P < 0.0001). Histologically, the normal structure
      of fatty tissues was found primarily in both groups. Our results indicate that
      although fatty tissues within adipose aspirates after conventional liposuction
      maintain normal structure with near the same number of viable fatty cells
      compared with fresh ones, they have a less-than-optimal level of cellular
      function and may not survive well after they are transplanted.

PMID- 15725839
TI  - The use of a bovine collagen construct for reconstruction of full-thickness scalp
      defects in the elderly patient with cutaneous malignancy.
AB  - Full-thickness defects of the scalp following cancer resection are reconstructive
      challenges when bone is exposed. Local, regional, and/or free tissue transfer
      have all been described for reconstruction when the pericranium is exposed. We
      examined the surgical outcomes from 23 patients who underwent placement of bovine
      collagen constructs. Thereafter, delayed skin grafting was performed. The average
      age of the patients was 70 years. All patients had one of the following: melanoma
      (n = 13) squamous cell carcinoma (n = 5), angiosarcoma (n = 2), basal cell
      carcinoma (n = 1), spindle cell carcinoma (n = 1), or malignant pilar tumor (n =
      1). The average defect size was 51 cm, with a range of 9 cm to 169 cm. Average
      time between bovine construct placement and skin grafting was 30 days. Histologic
      studies demonstrated persistence of the construct and infiltration of nascent
      fibroblasts. Six patients had delayed healing due to microabscesses in the
      constructs. All wounds eventually healed. In the elderly, this is a simple method
      to treat full-thickness scalp defects.

PMID- 15725837
TI  - Halofuginone inhibits collagen deposition in fibrous capsules around implants.
AB  - Fibrous capsule formation around implants remains a difficult problem that has
      been studied for decades. The etiology is elusive, but the end result is the
      deposition of a dense collagenous capsule around implanted materials. The purpose
      of this study was to determine the effects of a type I collagen synthesis
      inhibitor, halofuginone, on fibrous capsule formation around implanted materials.
      Silastic disks were implanted subcutaneously into 4 groups of adult male rats for
      up to 8 weeks. Group 1 received drug throughout the study, group 2 received drug
      during the first half only, group 3 received drug during the second half only,
      and the control group received no drug. Implants were removed and histology of
      the capsules was examined. A collagen index score was calculated from digital
      images of trichrome-stained histologic sections, which permitted semiquantitative
      comparison of collagen content among the 4 groups. The collagen index values
      clearly indicate that halofuginone effectively inhibited collagen deposition
      within the capsule around the implanted disks. Halofuginone treatment also
      resulted in a decrease in the collagen index score in rat skin, indicating that
      halofuginone may affect preexisting collagenous structures. The ability of
      halofuginone to inhibit collagen deposition in new and preexisting fibrous
      capsules suggests that it may be a useful adjunct to minimize the formation of
      capsules around implantable prostheses.

PMID- 15725840
TI  - Enhanced survival using the distally based sural artery interpolation flap.
AB  - The reverse sural artery flap is frequently used for reconstruction of the distal
      third of the leg, ankle, and heel. The major disadvantage of the flap is
      compression of the pedicle within the subcutaneous tunnel and venous congestion.
      Others have cited a decrease in this problem by harvesting a midline cuff of
      gastrocnemius muscle, including more subcutaneous tissue and using a wider-than
      usual pedicle. We describe an interpolation flap technique of simply avoiding a
      subcutaneous tunnel and exteriorizing the pedicle with no other alterations to
      flap design or elevation techniques. Seven distally based reverse sural artery
      flaps were performed on ambulatory patients between 2001 and 2002. Venous
      congestion did not occur in any of the flaps. All patients were ambulatory after
      surgery and did not require the use of a custom shoe. We conclude that
      transferring the flap in 2 stages without the use of a tunnel improves the
      reliability of the flap and eliminates venous congestion.

PMID- 15725841
TI  - A new anatomical repair method for the treatment of ingrown nail: prospective
      comparison of wedge resection of the matrix and partial matricectomy followed by
      lateral fold advancement flap.
AB  - Currently, there are various surgical treatment modalities for ingrowing nail.
      None of these procedures are perfect to achieve esthetic results with low cost,
      recurrence, and complication rates. Eighty-seven toenails of 77 patients were
      operated in our clinic; 49 wedge matrix resections (WMR) and 38 partial
      matricectomy followed by lateral fold advancement flap (LFAF) were applied.
      Average follow-up period of the patients was 13 months. The recurrence rates,
      spicule formation, immobilization periods, and patient satisfaction for cosmetic
      result and discomforting symptoms were investigated. Nail, distal phalanx bone,
      soft tissue measurements were performed in the counterlateral healthy toe of 34
      patients that we operated due to the unilateral ingrowing nail and 34 randomized
      individuals with no ingrowing nail by lateral and anteroposterior toe x-rays.
      There were no significant differences for age, sex, the side of the ingrowing
      nail, postoperative mobilization period, and the follow-up period between 2
      groups that the techniques were applied to. There was no statistically
      significant difference in WMR (8.1%, 4 toes) and LFAF (none) for the recurrence
      rate. But there was significant difference between WMR (36.7%, 18 toes) and LFAF
      (5.2%, 2 toes) for the spicule formation rates (P < 0.05), and there was
      significant difference between WMR (20.4%, 10 toes) and LFAF (none) for the
      reoperation (P < 0.03). It was observed that patient satisfaction in cosmetic
      view was better in patient group treated with LFAF (P < 0.05). Phalanx heads were
      wider in patient group with ingrowing nail at the results of the measurements (P
      < 0.01). The fact that granulation and scarred tissues are removed instead of
      performing the great soft tissue excisions is more correct for both recurrence
      and cosmetics. Partial matricectomy and LFAF is a good alternative method for the
      treatment of ingrown nail, with less recurrence rates and cost and better
      cosmetic results.

PMID- 15725843
TI  - The expression of proinflammatory cytokines in the rat muscle flap with ischemia
      reperfusion injury.
AB  - Ischemic-reperfusion injury mediated by free radicals and neutrophils is the
      principal pathway for tissue injury and death. Cytokines influence activity of
      various cell types during the inflammatory process. In this study, expression of
      selected proinflammatory cytokines was examined in primary and secondary ischemia
      in the rat gracilis flap model. Sixty Sprague-Dawley rats were used in the study.
      Primary ischemia of each gracilis flap was induced by clamping its vascular
      pedicle for 1 hour. The flap was then replaced and allowed to reperfuse. Twenty
      four hours later, a secondary ischemia was induced via vascular clamping for 4
      hours. All muscle flaps were biopsied at 4 hours and 18 hours after primary
      ischemia. After secondary ischemia, each flap was biopsied immediately postevent,
      at 4 hours, and at 18 hours. Expression of tumor necrosis factor (TNF-alpha),
      interleukin (IL-1beta), and platelet-derived growth factor (PDGF) mRNA was
      determined by RT-PCR in each case. An equal sample size of gracilis muscle flaps,
      elevated in an identical fashion but not subjected to vascular clamping, was
      examined for baseline gene expression. Results showed that TNF-alpha gene
      expression was significantly up-regulated at 18 hours after secondary ischemia.
      IL-1 gene expression was up-regulated at 4 hours after primary ischemia, and was
      greatest at 4 hours after secondary ischemia. PDGF expression was up-regulated
      immediately after secondary ischemia, then at 4 hours after secondary ischemia (P
      < 0.05), and down-regulated during reperfusion. This study delineated changes in
      the expression of TNF-alpha, IL-1beta, and PDGF mRNA, in both primary and
      secondary ischemia and reperfusion episodes at several critical time points.

PMID- 15725844
TI  - Extracorporeal bypass preserved composite anterior thigh free flap (periosteo
      musculo-fascio-cutaneous) for hemipelvectomy reconstruction: utilizing the
      periosteal component for abdominal wall fascial reconstruction.
AB  - We present a case of a right external hemipelvectomy for chondroblastic
      osteosarcoma originating from the right ilium and reconstruction with salvage
      parts; cardiopulmonary bypass preserved anterior thigh free flap. The resection
      required sacrifice of the right common iliac artery and vein and the entire right
      gluteus maximus muscle. The first stage of the procedure was a high above-knee
      amputation on the ipsilateral leg. The amputated extremity was placed on
      extracorporeal bypass utilizing the common femoral artery and vein. This
      technique, previously unreported, supported the successful utilization of the
      anterior thigh free flap for both soft tissue and abdominal wall facial
      reconstruction.

PMID- 15725845
TI  - Successful upper alveolar reconstruction for gingival cancer using a fibular
      osteoadipofascial flap without osseointegrated implants.
AB  - An upper alveolar skeletal reconstruction with closure of the palatal fistula
      using an osteocutaneous free flap is considered an ideal reconstructive strategy
      after curative surgery for cancer of the lower maxilla. Although installation of
      osseointegrated implants into the bone has advantages for utilizing a dental
      prosthesis, it is often time and cost prohibitive. In the case of 1 patient, we
      reconstructed and fit the patient with a conventional denture, eliminating the
      need for installation of osseointegrated implants. The patient underwent upper
      alveolar reconstruction using a fibular osteoadipofascial flap, followed by a
      skin graft for creation of an alveololabial sulcus. It was then possible for the
      patient to wear a conventional denture without implants. One explanation for this
      success is that the regenerated mucosa on the adipofascial flap and skin graft
      was immobile, which allowed it to serve as a base for the dental prosthesis. The
      alveololabial sulcus that had been constructed kept the denture in place. This
      reconstruction confirmed that a fibular osteoadipofascial flap might be a useful
      choice in restoring a natural upper alveolar osseous and soft tissue structure.

PMID- 15725846
TI  - Management of airway obstruction in a severe case of juvenile hyaline
      fibromatosis.
AB  - Juvenile hyaline fibromatosis (JHF) is an extremely rare, genetic disease with
      unknown etiology. It is characterized by cutaneous nodules and flexural joint
      contractures, along with hypertrophy of the gingival and oral mucosa, which is
      probably the most striking and morbidity-related feature of the disease. An
      advanced case of JHF with prominent growth retardation, recurrent respiratory
      tract infections, and impending upper respiratory tract obstruction due to severe
      hypertrophy of the oral mucosa and gingiva is presented. Surgical excision of the
      hypertrophic oral mucosa and cutaneous nodules in the scalp was performed. No
      major recurrence of the mucosal lesions was observed at the first postoperative
      year.

PMID- 15725847
TI  - Optic nerve decompression via mid-facial translocation approach.
AB  - Optic neuropathy is a disease complex with a broad range of etiologies that have
      a common end point if left untreated: blindness. Treatment varies from expectant
      management, medical therapy, to surgical treatment. We present a new technique
      for optic nerve decompression using a midfacial translocation approach. We
      present a case where this technique was used twice to decompress the optic nerve
      from an encroaching fibrous dysplasia in the same eye. Patient's vision had
      deteriorated to near blindness each time and it improved to its preoperative
      level after each surgery. This technique is especially useful in cases where the
      local anatomy and relevant landmarks have been distorted by the pathologic
      process and the surgeon requires a good exposure with minimal morbidity.

PMID- 15725849
TI  - Of love and war.

PMID- 15725848
TI  - Hemophilia B and free tissue transfer: medical and surgical management.
AB  - Hemophilia B (Christmas disease) is a rare, X-linked bleeding diathesis, which
      may present with life-threatening hemorrhage. Management of the coagulopathy in
      the setting of free tissue transfer may be particularly challenging. The authors
      present the first case in the English literature of a male with hemophilia B
      undergoing microvascular free flap reconstruction, as well as a review of the
      current surgical and medical management of hemophilia B. Based upon this
      experience, perioperative specific factor replacement is recommended. Given
      physiologic trough levels of the replaced factor, routine antiplatelet therapy
      appears appropriate. Management of free tissue transfer in the setting of severe
      hemophilia is significantly more challenging and should benefit from
      multidisciplinary coordination.

PMID- 15725852
TI  - Approach to the pregnant patient with headache.

PMID- 15725853
TI  - Eclampsia: morbidity, mortality, and management.

PMID- 15725854
TI  - The clinical management of intracranial neoplasms in pregnancy.

PMID- 15725855
TI  - Pregnancy and multiple sclerosis.

PMID- 15725856
TI  - Myasthenia gravis and pregnancy.

PMID- 15725857
TI  - Peripheral neuropathies during pregnancy.

PMID- 15725858
TI  - Traumatic spinal cord injury.

PMID- 15725861
TI  - Guidelines for cervical cancer screening: history and scientific rationale.

PMID- 15725862
TI  - The Bethesda System 2001: update on terminology and application.

PMID- 15725863
TI  - Current cervical screening technology considerations: liquid-based cytology and
      automated screening.

PMID- 15725864
TI  - Evidence for the role of human papillomavirus DNA testing in primary screening
      for cervical dysplasia.

PMID- 15725865
TI  - The role of self-collection devices for cytology and human papillomavirus DNA
      testing in cervical cancer screening.

PMID- 15725867
TI  - Current management of low-grade squamous intraepithelial lesion, high-grade
      squamous epithelial lesion, and atypical glandular cells.

PMID- 15725866
TI  - Current techniques for the evaluation of abnormal cervical cytology.

PMID- 15725868
TI  - Management of women with cervical cytology interpreted as ASC-US or as ASC-H.

PMID- 15725869
TI  - Special situations: abnormal cervical cytology during pregnancy.

PMID- 15725870
TI  - Special situations: abnormal cervical cytology in immunocompromised patients.

PMID- 15725871
TI  - Controversial topics in abnormal cervical cytology: "see and treat".

PMID- 15725872
TI  - The clinical utility of the diagnostic endocervical curettage.

PMID- 15725873
TI  - Emerging technology in cervical cancer screening: spectroscopy.

PMID- 15725875
TI  - Human papillomavirus vaccine: history, immunology, current status, and future
      prospects.

PMID- 15725874
TI  - Emerging technology in cervical cancer screening: status of molecular markers.

PMID- 15725878
TI  - Outcome analysis of cataract surgery following therapeutic keratoplasty.
AB  - PURPOSE: To assess the results of cataract surgery, in terms of visual outcome
      and effect on graft survival, in eyes that have previously undergone therapeutic
      penetrating keratoplasty for infective keratitis. METHODS: Case records of
      patients who had undergone cataract surgery alone (group A) or in combination
      with regrafting (group B) following initial therapeutic penetrating keratoplasty
      between January 2000 and December 2001 were reviewed retrospectively. Main
      outcome measures studied were visual acuity, astigmatism, and effect of the
      cataract surgery on graft survival. Results were compared with eyes undergoing
      cataract surgery after optical keratoplasty and between eyes in groups A and B.
      RESULTS: Frequency of cataract surgery after therapeutic keratoplasty was
      significantly greater than that following optical keratoplasty [68 (52%) versus
      47 (21%); P<0.001]. Fifty-eight eyes of 58 patients undergoing cataract surgery
      after therapeutic penetrating keratoplasty were analyzed in detail. Mean follow
      up period was 8.9 months (+/-7.6 months). Thirty eyes underwent cataract surgery
      alone (group A), and 28 eyes underwent cataract surgery with regrafting (group
      B). Eyes that had undergone therapeutic keratoplasty were significantly more
      likely to have opaque grafts requiring regrafting at the time of cataract surgery
      than eyes that had undergone optical keratoplasty [28 (48.3%) versus 5 (10.6%);
      P<0.001]. Incidence of graft failure after cataract surgery did not differ
      significantly in eyes that had undergone therapeutic or optical keratoplasty.
      Final visual acuity at last follow-up was 6/12 or better in 25 eyes (43%). There
      were no significant differences between eyes in groups A and B in terms of final
      visual acuity, astigmatism, or graft failure rates. CONCLUSIONS: Visual results
      of cataract surgery following therapeutic keratoplasty are comparable to those
      following optical keratoplasty. Combining a repeat keratoplasty for a failed
      graft with the cataract surgery does not significantly affect the final outcome.

PMID- 15725879
TI  - Histopathological findings of epithelial ingrowth after laser in situ
      keratomileusis.
AB  - PURPOSE: To investigate the histopathological features of epithelial ingrowth
      after laser in situ keratomileusis (LASIK). METHODS: Five epithelial ingrowth
      specimens of 4 patients (2 to 17 months after initial LASIK) were examined. The
      lesions were surgically removed and examined using light and transmission
      electron microscopy. RESULTS: Early epithelial ingrowth was clinically observed
      as faint opacities with demarcation lines and epithelial pearls. Late epithelial
      ingrowth was observed as homogeneous whitish masses. Histopathologically, early
      epithelial ingrowth consisted of multilayered squamous epithelium resembling
      normal corneal epithelium, whereas late ingrowth was made up of clumps containing
      amorphous materials with scarce cellular elements. CONCLUSIONS: Our findings
      suggest that clinical appearance and histopathology of epithelial ingrowth from
      LASIK flap margins differ in early and late stages, which might reflect
      proliferative activity of the lesions.

PMID- 15725880
TI  - Influence of cataract surgery on corneal endothelial cell density estimation.
AB  - PURPOSE: To assess the effect of cataract surgery on semiautomated human corneal
      endothelial cell density (ECD) estimation using noncontact specular microscopy.
      METHODS: In this prospective clinical study, 62 consecutive patients undergoing
      cataract surgery were studied. To evaluate possible variations of accuracy and
      agreement under clinical circumstances, the corneal ECD was determined before and
      after cataract surgery. The parameter ECD (cells/mm) in the central and
      paracentral cornea was consecutively determined with 2 algorithms available in a
      noncontact specular microscope [fixed-frame method (FFM) and automatic center
      method (ACM)]. The postoperative evaluation was performed at 1 day, after 4
      weeks, and after 6 months. The accuracy, the relative error, and the 95% limits
      of agreement (LoA) were determined for both counting methods. RESULTS: The
      overall group-averaged accuracy was -19.4 cells/mm (0.86%) centrally and -17.3
      cells/mm (0.76%) paracentrally. The LoA (95% CI) were within 234 cells/mm (10.4%)
      and 250 cells/mm (10.9%), respectively. After cataract surgery, a slight decrease
      in accuracy was noted in the central (2.09%) and paracentral areas (1.76%). The
      relative error increased from 3.66% to 6.02% centrally and from 4.96% to 6.55%
      paracentrally. The LoA (95% CI) increased from +/-194 cells/mm to +/-304 cells/mm
      centrally and from +/-275 cells/mm to +/-322 cells/mm paracentrally. In the later
      postoperative period, endothelial stabilization improved the accuracy and
      agreement in ECD estimation. CONCLUSIONS: The estimation of ECD after cataract
      surgery employing current algorithms was achieved with a clinically acceptable
      level of accuracy and agreement. However, the analysis of images in the early
      postoperative period as well as paracentral corneal areas revealed larger
      variabilities. This revealed that the FFM and ACM counting methods cannot be used
      interchangeably under all circumstances. The ACM seemed preferable when only low
      quality images were available and permitted determination of additional
      qualitative endothelial cell parameters.

PMID- 15725881
TI  - Comparison of amniotic membrane graft alone or combined with intraoperative
      mitomycin C to prevent recurrence after excision of recurrent pterygia.
AB  - PURPOSE: Without effective adjunctive therapy, the recurrence rate after excision
      of recurrent pterygia is high. In an effort to determine a way to better reduce
      the recurrence of pterygia, we compared the efficacy and safety of amniotic
      membrane graft (AMG) alone and AMG combined with intraoperative mitomycin C after
      excision of recurrent pterygia. METHODS: Patients with recurrent pterygia were
      randomly assigned to receive excision of pterygia followed by AMG alone or AMG
      combined with intraoperative 0.025% mitomycin C for 3 minutes (AMG-mitomycin C).
      Patients who could be followed up for more than 12 months were entered for data
      analysis. Conjunctival (potential) and corneal (true) recurrence of pterygia and
      other complications were recorded. RESULTS: The group receiving AMG alone was
      made up of 48 eyes in 48 patients, and the group receiving AMG-mitomycin C
      consisted of 47 eyes in 46 patients. No significant difference was found in age
      distribution, sex distribution, or duration of follow-up between the 2 groups.
      Regarding the recurrence rates of each group, 6 conjunctival (12.5%) and 6
      corneal (12.5%) recurrences developed in the AMG group, and 4 conjunctival (8.5%)
      and 6 corneal (12.8%) recurrences developed in the AMG-mitomycin C group. No
      significant difference was found in the conjunctival and corneal recurrence rate
      between the 2 groups (P=0.623 and 0.966, respectively; log rank test), and no
      major complications developed in either group. CONCLUSIONS: AMG alone can be
      considered an effective alternative adjunctive treatment of recurrent pterygia.
      The addition of intraoperative mitomycin C did not further reduce the recurrence
      rate.

PMID- 15725882
TI  - Candidate gene screening for posterior polymorphous dystrophy.
AB  - PURPOSE: To perform candidate gene screening for posterior polymorphous corneal
      dystrophy (PPCD). The initial 3 genes chosen, ID1, BCL2L1, and VSX1, lie within
      the region on chromosome 20 to which the PPCD gene has been linked, and mutations
      in VSX1 have previously been identified in patients with PPCD. METHODS: DNA
      extraction, PCR amplification, and direct sequencing of the VSX1, BCL2L1, and ID1
      genes were performed in 14 affected patients (12 families) as well as in
      unaffected family members and healthy control subjects. RESULTS: No coding region
      mutations in the BCL2L1 or ID1 genes were identified in affected patients. In the
      VSX1 gene, the previously identified Gly160Asp missense change was not present in
      any of our 12 probands, and the Asp144Glu mutation was identified in 1 affected
      patient as well as 1 unaffected control individual. Additionally, 2 synonymous
      substitutions were identified, Ala182Ala (8 affected patients from 8 families)
      and Gly239Gly (1 affected patient and 1 unaffected patient from the same family).
      In the ID1 gene, the synonymous substitution Gly216Gly was observed in 2 affected
      patients (2 families) who also demonstrated a single nucleotide change in both
      the 5'UTR (2129T>C) and 3'UTR (3267A>G). Another 5'UTR change, 2177T>C, was
      identified in 1 affected patient and his unaffected parent, both of whom also
      demonstrated the 2129T>C and 3267A>G changes. CONCLUSIONS: None of the 12
      probands with PPCD demonstrated the previously described Gly160Asp mutation
      within the VSX1 gene. The Asp144Glu missense change, present in an affected
      patient as well as an unaffected control individual, appears to be a rare
      polymorphism, not a disease-causing mutation. No coding region changes were
      identified in the ID1 or BCL2L1 genes. Therefore, although we report a number of
      novel polymorphisms in the VSX1 and ID1 genes, the failure to identify any
      sequence variants that sort with the disease phenotype suggests that other
      genetic factors are involved in PPCD.

PMID- 15725883
TI  - Microbial keratitis in prospective studies of extended wear with disposable
      hydrogel contact lenses.
AB  - PURPOSE: To report the annualized incidence of microbial keratitis with extended
      wear of low oxygen transmissible (Dk/t) disposable soft contact lenses from
      prospective postmarket clinical trials. METHODS: Seven hundred ninety subjects
      were enrolled at the L.V. Prasad Eye Institute (LVPEI), Hyderabad, India from
      March 1993 to March 2000, resulting in 1231 patient eye years, and 167 subjects
      were enrolled at the Cornea and the Contact Lens Research Unit (CCLRU), Sydney,
      Australia from July 1987 to December 1999, resulting in 842 patient eye years.
      RESULTS: The annualized incidence of microbial keratitis per 10,000 eyes per year
      of lens wear was 32.5 (95% CI 8.9 to 83.2) for LVPEI, 23.8 (95% CI=2.9 to 85.8)
      for CCLRU; when data are combined across both centers, the incidence was 28.9
      (95% CI=10.6 to 63) per 10,000 eyes per year of lens wear. This equates to 57.0
      per 10,000 wearers or 1 in 173 wearers per year of lens wear. All events were
      rated as slight to moderate in severity and did not result in visual loss. Two
      events were described to highlight the challenges in diagnosis and treatment of
      microbial keratitis. CONCLUSIONS: The incidence of microbial keratitis with
      extended wear of low-Dk/t disposable lenses was higher in these prospective
      studies (1 in 210 wearers per year at CCLRU and 1 in 154 wearers per year at
      LVPEI) than that seen in retrospective population-based surveillance studies (1
      in 500 wearers per year). Practitioners and patients should always be alert to
      signs and symptoms, and practitioners should adopt conservative strategies for
      diagnosis and management of contact lens-related adverse events.

PMID- 15725884
TI  - Observations of banding patterns (Vogt striae) in keratoconus: a confocal
      microscopy study.
AB  - PURPOSE: To investigate Vogt striae in keratoconus using confocal microscopy.
      METHODS: The central cornea of 51 eyes of 29 subjects with keratoconus was
      observed using a slit-lamp biomicroscope, slit-scanning confocal microscope
      (TOMEY Confoscan 1), and corneal topographer (EyeSys 2000). RESULTS: Alternating
      dark and light bands were seen in the stromal images of 23 eyes examined. The
      bands corresponded with the appearance of Vogt striae on slit-lamp biomicroscopy
      examination. Bands were found most commonly in the posterior stroma. Posterior
      bands varied in width, ran mainly in a nearly vertical direction, and appeared to
      run a straight course through individual image frames. Keratocyte nuclei were
      located in between the bands. Posterior keratocyte density was unaffected by the
      presence of bands. Nerve fibers appeared to run a straight course through the
      bands. When present, bands in the anterior stroma showed greater variability in
      width and direction within a single frame. Bands were only present in the
      anterior stroma in more severe levels of keratoconus. The difference in banding
      pattern noted between the anterior and posterior stroma parallels the known
      collagen fiber arrangement in the anterior and posterior stroma. CONCLUSIONS: The
      bands apparent on confocal microscopy of the stroma of the keratoconic cornea
      correspond with Vogt striae on slit-lamp microscopy. It appears that these bands
      (and hence Vogt striae) represent collagen lamellae under stress. The stress
      pattern appears to radiate from the center of the cone and is consistent with the
      direction of striae when viewed with the confocal microscope.

PMID- 15725885
TI  - Topography-based screening for previous laser in situ keratomileusis to correct
      myopia and hyperopia.
AB  - PURPOSE: To develop a screening tool based on corneal topography to detect
      previous myopic and hyperopic laser in situ keratomileusis (LASIK). METHODS:
      Clinical data from three private clinics were analyzed in a university setting. A
      total of 476 topographies (Orbscan II) were randomly selected (1 topography per
      patient): 338 from unoperated corneas, 81 from corneas that had LASIK to correct
      myopia, and 57 from corneas that had LASIK to correct hyperopia. The LASIK
      procedures were performed using a Technolas excimer laser (217C or 217Z) and a
      Hansatome microkeratome. The first set of algorithms (VESm and VESh) calculated
      the volume summation between the anterior corneal surface and the best-fit sphere
      in the central and mid-peripheral regions. The second set of algorithms (DCm and
      DCh) calculated the mean anterior tangential curvature difference between the
      central and mid-peripheral regions. RESULTS: The features VESm and DCm for the
      screening of a myopic LASIK yield, respectively, sensitivity rates of 92.7% and
      95.1% and specificity rates of 94.9% and 96.5%. The features VESh and DCh for the
      screening of a hyperopic LASIK gave sensitivity rates of 93.1% for both and
      specificity rates of 94.8% and 97.1%. The performance of those features was
      superior to clinical assessment using topography color maps. CONCLUSIONS:
      Criteria based on Orbscan II corneal topography are proposed for the detection of
      previous hyperopic and myopic LASIK performed with a Technolas excimer laser
      (version 217C or 217Z).

PMID- 15725886
TI  - Deep lamellar keratoplasty (DLKP) in keratoconus patients using viscoadaptive
      viscoelastics.
AB  - PURPOSE: To demonstrate the effectiveness and safety of using viscoadaptive
      viscoelastics in deep lamellar keratoplasty (DLKP) for keratoconus. METHODS: A
      nonrandomized, comparative, interventional case series was performed on 12 eyes
      of 10 consecutive keratoconus patients without a history of acute hydrops.
      Patients were treated with DLKP using ophthalmic viscosurgical devices (OVDs) to
      dissociate Descemet membrane (DM) from the stroma before suturing of the donor
      cornea. Eight eyes were operated using Viscoat (dispersive), and 4 eyes were
      operated using Healon V (viscoadaptive). RESULTS: Six out of 8 eyes in the
      Viscoat group were successfully treated, and 2 eyes were converted to PKP because
      of tears in the DM. Another 3 eyes had double chambers as a result of
      perforations or tears in DM, which were treated by injecting air into the
      anterior chamber. All 4 eyes in the Healon V group were successfully operated,
      with 1 case with microperforation of DM during suturing. Healon V offered better
      control of the area to be dissociated and served as a pseudostroma that protects
      the exposed DM while the overlying stroma is maneuvered. CONCLUSION: Healon V is
      a valuable tool for performing DLKP in difficult cases such as keratoconus.

PMID- 15725887
TI  - Efficacy of systemic cyclosporine A and amniotic membrane on rabbit conjunctival
      limbal allograft rejection.
AB  - PURPOSE: To evaluate the effect of intramuscular cyclosporine A (CsA) and
      amniotic membrane (AM) on conjunctival limbal allograft survival in a rabbit
      model. METHODS: Eighty-two female rabbits (59 New Zealand white rabbits, 23 Dutch
      pigmented rabbits) were used. The New Zealand white rabbits were divided into 4
      treatment groups: group 1 (n=13), conjunctival limbal autograft transplantation;
      group 2 (n=12), conjunctival limbal allograft transplantation without additional
      treatment; group 3 (n=18), conjunctival limbal allograft transplantation and
      human AM; and group 4 (n=16), conjunctival limbal allograft transplantation and
      systemic CsA (10 mg/kg/day intramuscularly). The 23 Dutch pigmented rabbits were
      used as limbal stem cell allograft donors. The rejection index, the mean survival
      time, and the rejection rates were calculated for each group. RESULTS: After 28
      days of follow-up, there were no episodes of limbal rejection in groups 1 and 4,
      whereas the rejection rate was 100% in groups 2 and 3. There was no significant
      difference in mean survival time of the rejected grafts between groups 2 and 3.
      CONCLUSIONS: A model of rejection of conjunctival limbal transplantation was
      developed in the rabbit. Intramuscularly injected CsA effectively prevents limbal
      allograft rejection. Human AM is not useful for this purpose.

PMID- 15725888
TI  - Surface pressure measurements of human tears and individual tear film components
      indicate that proteins are major contributors to the surface pressure.
AB  - PURPOSE: Tear film stability has been associated with a low surface tension (high
      surface pressure), which has been attributed to a variety of tear film
      components. In this study, we examined the contribution of various tear proteins,
      mucin, and meibomian lipids to the surface pressure of human tears. METHODS: A
      Langmuir trough was used to measure and compare the surface activities of
      albumin, lipocalin, beta-lactoglobulin, lactoferrin, lysozyme, secretory IgA,
      mucin, meibomian lipid, and tears. RESULTS: All proteins exhibited surface
      activity. The surface pressure-area (Pi-A) profiles of most protein films at
      equilibrium surface pressure (Pieq) were sigmoidal and showed hysteresis between
      the expansion and compression phases of the cycle. Pieq of most proteins took 4-9
      hours to occur. By contrast, the Pi-A profiles for meibomian lipid films were
      hyperbolic rather than sigmoidal and had little hysteresis, and Pieq was attained
      within 1 hour. The Pi-A profiles of mucin films showed mostly hyperbolic
      characteristics with small hysteresis. The Pi-A profiles of films of tears were
      sigmoidal, showed strong hysteresis, and reached Pieq at about 5 hours.
      Partitioning of the proteins and whole tears into the subphase also occurred.
      CONCLUSION: Comparison between the dynamic Pi-A profiles of tears and those of
      individual tear film components shows that tear film proteins not only are
      capable of surface activity but also are major contributors to the surface
      activity of the tear film.

PMID- 15725889
TI  - Comparative efficacy of topical moxifloxacin versus ciprofloxacin and vancomycin
      in the treatment of P. aeruginosa and ciprofloxacin-resistant MRSA keratitis in
      rabbits.
AB  - PURPOSE: To evaluate the in vivo efficacy of topical moxifloxacin 0.5% versus
      ciprofloxacin 0.3% in the treatment of Pseudomonas aeruginosa keratitis and
      topical moxifloxacin 0.5% versus vancomycin 50 mg/mL in the treatment of
      ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus (MRSA)
      keratitis in rabbits. METHODS: Experimental bacterial keratitis was induced in
      rabbits by corneal intrastromal injection. Infection proceeded for 12 hours,
      after which topical antibiotics were applied hourly for 12 hours. Corneal
      homogenates were plated with serial dilutions for quantitative bacteriology.
      RESULTS: Both moxifloxacin and ciprofloxacin performed significantly better than
      control in the treatment of Pseudomonas aeruginosa keratitis (P=0.0046 and
      0.0069, respectively); there were no significant differences between these 2
      drugs in bactericidal activity (P=0.1120). Moxifloxacin performed significantly
      better than control in the treatment of ciprofloxacin-resistant MRSA (P=0.0321)
      keratitis, and vancomycin showed a trend toward statistical significance in
      performing better than control (P=0.0576); there were no significant differences
      between these 2 drugs in bactericidal activity (P=0.5205). CONCLUSIONS: Topical
      moxifloxacin 0.5% and ciprofloxacin 0.3% have similar efficacy in the treatment
      of Pseudomonas aeruginosa keratitis in rabbits. Topical moxifloxacin 0.5% and
      vancomycin 50 mg/mL have similar efficacy in the treatment of ciprofloxacin
      resistant MRSA keratitis in rabbits. These results suggest a potential value for
      topical moxifloxacin as a broad-spectrum agent in the treatment of bacterial
      keratitis.

PMID- 15725890
TI  - Hyaluronic acid-CD44 interaction mediates the adhesion of lymphocytes by amniotic
      membrane stroma.
AB  - PURPOSE: To demonstrate the role of intrinsic hyaluronic acid (HA) in the
      entrapment of inflammatory cells by amniotic membrane (AM) in vitro. METHODS: HA
      concentration in AM was analyzed by the sandwich protein binding assay, and the
      approximate molecular weight was measured by gel filtration chromatography. To
      localize HA in AM tissue, toluidine blue staining with and without hyaluronidase
      treatment was performed. Adhesion of the lymphocyte cell lines, Jurkat and Molt
      4, and peripheral blood mononuclear cells (PBMC) to AM and HA-coated glass slides
      was analyzed in an in vitro binding assay. Flow cytometry was performed to
      quantify the expression of the HA receptor, CD44, in Jurkat, Molt 4, and PBMC.
      RESULTS: HA was present in high levels in the stroma of AM, also demonstrated by
      intense staining with toluidine blue. Staining was inhibited by both
      hyaluronidase treatment and acidic pH. Molt 4, which constitutively expressed
      CD44, bound to AM and HA-coated slides significantly more than Jurkat cells (CD44
      ). Adhesion of Molt 4 was inhibited by pretreatment with both soluble HA and anti
      CD44 antibody. LPS- or TNF-alpha-treated PBMC also bound to AM and HA-coated
      slides and was inhibited by pretreatment with an anti-CD44 antibody. CONCLUSION:
      HA in AM stroma may play an important role in the entrapment of inflammatory
      cells including lymphocytes when used as a patch in ocular surface disease.

PMID- 15725891
TI  - Carteolol hydrochloride protects human corneal epithelial cells from UVB-induced
      damage in vitro.
AB  - PURPOSE: To investigate whether carteolol hydrochloride has protective effects
      against ultraviolet B (UVB)-induced damage in human corneal epithelial cells
      (HCECs). METHODS: Cultured HCECs were exposed to a single dose of UVB 300 mJ/cm,
      and the cell viability was measured 12 hours after the UVB irradiation using a
      cell-counting kit. Test samples at 0.01-1.0 mmol/L (carteolol hydrochloride,
      timolol maleate, betaxolol hydrochloride, levobunolol hydrochloride, or
      nipradilol) were added to the HCECs before, during, or after UVB irradiation. UV
      absorption spectra for each drug sample were determined using a
      spectrophotometer. Hydrogen peroxide (H2O2) and carteolol hydrochloride were
      simultaneously added to the HCECs for 10 minutes, and the cell viability was
      measured 12 hours later. The ability of carteolol hydrochloride to scavenge
      superoxide anion (O2) and singlet oxygen (O2) was investigated using the MCLA
      chemiluminescence method. RESULTS: UVB irradiation decreased the number of viable
      HCECs in a dose-dependent manner. Carteolol hydrochloride at 1 mmol/L attenuated
      the UVB-induced cell damage when added before, during, or after UVB irradiation
      (P<0.01). Levobunolol hydrochloride at 1 mmol/L (P<0.01) added during or after
      irradiation and timolol maleate at 0.1 mmol/L or higher (P<0.05) added during
      irradiation attenuated the UVB-induced cell damage. Betaxolol hydrochloride and
      nipradilol had no effect. The UV absorption spectra of timolol maleate and
      levobunolol hydrochloride overlapped with the UVB wavelength spectrum, while
      carteolol hydrochloride, betaxolol hydrochloride, and nipradilol showed a partial
      overlap. Carteolol hydrochloride at 1 mmol/L (P<0.05) significantly inhibited
      H2O2-induced cell damage and was able to scavenge O2 (EC50 value: 48 mmol/L).
      CONCLUSIONS: These data strongly suggest that carteolol hydrochloride has a
      protective action against UVB-induced HCEC damage, and its radical scavenging
      ability may be an important basis for this effect.

PMID- 15725892
TI  - Macular edema and iridocorneal endothelial syndrome: a case report.
AB  - PURPOSE: To report a case of cystoid macular edema (CME) in iridocorneal
      endothelial syndrome. METHODS: Case report. RESULTS: The authors describe the
      clinical history and ocular examination of a 38-year-old woman with iridocorneal
      endothelial syndrome and CME. This association has never been reported before.
      The mechanism of CME is unknown. CONCLUSION: CME may cause visual deterioration
      in iridocorneal endothelial syndrome. We emphasize the importance of posterior
      segment examination in these cases.

PMID- 15725894
TI  - Confocal microscopy used as the definitive, early diagnostic method in Chandler
      syndrome.
AB  - PURPOSE: To report the early, rapid diagnosis of the Chandler variant of the
      iridocorneal endothelial (ICE) syndrome using confocal light microscopy. METHODS:
      A 62-year-old man with a long history of unilateral glaucoma reported
      progressively blurred vision in his right eye. Examination of both eyes included
      visual acuity, slit-lamp examination, pneumotonometry, visual field, gonioscopy,
      and confocal microscopy. RESULTS: On examination, visual acuity was 20/80 and
      20/20 and the IOPs were 26 and 12. The anterior segment OD revealed 1+ inferior
      and axial corneal edema, while the OS was normal to biomicroscopy and posterior
      segment. Chandler syndrome or Fuchs endothelial dystrophy was suspected. In the
      affected eye, confocal light microscopy clearly showed an "epithelium-like"
      transformation of the corneal endothelium with irregularly shaped cells and
      hyperreflective nuclei, establishing the diagnosis of Chandler syndrome.
      CONCLUSIONS: In the presence of corneal edema or haze, corneal endothelium can be
      clearly visualized by confocal microscopy. "Epithelium-like" endothelial cells
      with highly reflective nuclei characteristic of Chandler syndrome were easily
      identified by confocal light microscopy to establish the diagnosis, despite the
      presence of corneal edema. Thus, confocal microscopy is a sensitive tool for the
      rapid, early diagnosis of ICE syndrome and may help distinguish among its
      variants.

PMID- 15725893
TI  - Management of prominent iris vascular tufts causing recurrent spontaneous
      hyphema.
AB  - PURPOSE: To report the management of recurrent, spontaneous hyphema associated
      with florid iris vascular tufts in a patient presenting for cataract surgery.
      METHODS: Interventional case report and review of the literature; presentation of
      clinical findings, iris angiography, and the argon laser regimen used to minimize
      potential corneal complications with increased total treatment energy. RESULTS:
      An 80-year-old man with a 20-year history of bilateral, recurrent, spontaneous
      hyphema associated with extensive iris vascular tufts presented with visually
      significant cataracts. Serial argon laser photocoagulation treatment of the
      prominent, circumferential iris vascular tufts of the left eye arrested further
      episodes of spontaneous hyphema and facilitated uneventful cataract surgery.
      Argon laser parameters were titrated to therapeutic effect during the initial
      treatment sessions, and sectoral photocoagulation of the circumferential vascular
      tufts was performed during a 5-month period to accommodate increased laser power
      and energy. The total energy required to complete treatment of the extensive
      lesions was substantially more than that in similar previous reports; however, no
      adverse corneal complications were associated with the laser therapy.
      CONCLUSIONS: This case appears to represent the first description of chronic,
      bilateral, recurrent spontaneous hyphema associated with iris vascular tufts.
      Argon laser treatment of symptomatic iris vascular tufts promotes resolution of
      recurrent, spontaneous hyphema and may serve to mitigate the risk of hemorrhage
      from these lesions during subsequent intraocular surgery. Conservative management
      of increased total treatment energy may minimize the potential risk of corneal
      decompensation with argon laser therapy.

PMID- 15725895
TI  - Laser in situ keratomileusis in patients with posterior polymorphous dystrophy.
AB  - PURPOSE: To report short-term results of LASIK in 4 eyes with the vesicular form
      of posterior polymorphous dystrophy (PPMD). METHOD: A review was performed of 2
      patients with PPMD who underwent bilateral LASIK. Patients were asymptomatic at
      the time of presentation and had no prior ocular history. Preoperative
      measurements were made of uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity (BSCVA), corneal pachymetry, and endothelial cell density
      (ECD). All 4 eyes underwent uneventful LASIK. Postoperative measurements of UCVA
      and BSCVA were performed at follow-up visits 1 day, 1 month, 3 months, and 1 year
      after surgery, along with pachymetry and ECD measurements at the 3-month and 1
      year visits. Results were analyzed. RESULTS: At 1 year, all eyes had an UCVA
      equal to or better than 20/25 and BSCVA equal to or better than 20/20. There was
      a small mean endothelial cell loss (2.3%) at 1 year. No adverse events were
      experienced. CONCLUSIONS: Short-term results indicate efficacy and safety of
      LASIK on eyes with posterior polymorphous dystrophy. Further study is needed to
      assess long-term outcomes in a larger study population.

PMID- 15725896
TI  - Histopathology of long-term Cardona keratoprosthesis: a case report.
AB  - PURPOSE: To report histologic findings of a Cardona keratoprosthesis (KPro) in an
      eye enucleated after 14 years. METHODS: Case report of a 56-year-old male whose
      KPro was implanted following bilateral chemical burns. Following enucleation,
      histopathology by light and transmission electron microscopy was performed.
      RESULTS: The prosthesis was retained in the eye until clinical complications
      including retinal detachment necessitated enucleation after 14 years.
      Histopathology confirmed a total retinal detachment, necrosis of the detached
      retina, inflammation, and foreign-body reaction in the Dacron mesh. Calcification
      was not seen. CONCLUSION: PMMA is a suitable material for an optic and provides
      for good postoperative acuity. The complex skirt area may be predisposed to long
      term inflammation. Less complicated surgery and a simple inert device with a
      flange with good mechanical and biologic integration may help in reducing
      postoperative complications.

PMID- 15725897
TI  - In vivo confocal microscopy in a patient with keratopigmentation (corneal
      tattooing).
AB  - PURPOSE: To report in vivo corneal confocal microscopic findings in a patient
      with keratopigmentation (corneal tattooing). PATIENTS AND METHODS: A 64-year-old
      woman who received keratopigmentation for bilateral corneal opacity 53 years ago
      was examined by confocal microscope. RESULTS: By confocal microscopy, scattered
      highly reflective particles in a geographic pattern were observed in the
      superficial stroma near Bowman layer. In addition, clusters of highly reflective
      granules were in the mid- to superficial stroma. CONCLUSIONS: In vivo confocal
      microscopy can be used for monitoring keratopigmentation. The findings may serve
      to distinguish keratopigmentations from other pigmented corneal lesions.

PMID- 15725898
TI  - Presumed stromal graft rejection after deep anterior lamellar keratoplasty.
AB  - PURPOSE: To demonstrate the development of presumed immune-mediated stromal
      rejection after deep anterior lamellar keratoplasty and its reversal after
      initiation of intensive topical corticosteroid therapy. METHODS: Observational
      case report carried out with the approval of the hospital institutional review
      board. RESULTS: Stromal edema and peripheral vascularization developed 16 months
      after deep anterior lamellar keratoplasty for keratoconus in a 13-year-old girl.
      After 2 weeks of intensive topical corticosteroids, complete reversal of stromal
      edema and regression of peripheral vascularization occurred, with full recovery
      of visual function. CONCLUSION: The clinical appearance and response to therapy
      in this case support the diagnosis of immune-mediated stromal rejection.
      Ophthalmologists should be aware that sight-threatening stromal rejection may
      occur in lamellar corneal grafts.

PMID- 15725899
TI  - Anemia of inflammation: the hepcidin link.
AB  - PURPOSE OF REVIEW: The anemia of inflammation has been associated for nearly two
      decades with elevated cytokine levels, but the primary mediator of this condition
      was unknown. Recently hepcidin antimicrobial peptide has emerged as the hormone
      that links the type II acute phase response to iron handling and erythropoiesis.
      RECENT FINDINGS: Hepcidin antimicrobial peptide likely modulates iron transport
      from macrophages and enterocytes to red blood cell precursors as a consequence of
      its interaction with SLC40A1/ferroportin, the only known transporter that
      facilitates iron egress. Insights into the regulation of hepcidin antimicrobial
      peptide expression by known iron metabolic proteins such as HFE, hemojuvelin, and
      transferrin receptor 2 are expanding the understanding of the genetic circuitry
      that controls iron absorption and utilization. SUMMARY: Increasingly, experiments
      suggest the hepatocyte is not just the iron storage depot but is the 'command
      central' for the maintenance of iron homeostasis. It receives multiple signals
      related to iron balance and responds via transcriptional control of hepcidin
      antimicrobial peptide.

PMID- 15725900
TI  - Polycythemia vera and other primary polycythemias.
AB  - PURPOSE OF REVIEW: Diagnosis and therapy of polycythemia vera are controversial
      since the molecular basis of polycythemia vera remains unknown. Distinguishing
      between polycythemia vera and other polycythemic disorders can be very
      challenging. The purpose of this review is to discuss the recent progress in this
      area and critically review the published data in context of our knowledge of
      other polycythemic disorders. RECENT FINDINGS: Erythropoietin is the principal
      regulator of regulator of erythropoiesis; its production is regulated by the
      degree of hypoxia. Our knowledge of cellular responses to hypoxia has recently
      exploded and led to the elucidation of the molecular basis of a polycythemia
      caused by augmentation of hypoxic sensing, Chuvash polycythemia. Similar progress
      in understanding the molecular basis of polycythemia vera has been elusive. A
      simple, readily available laboratory test to establish a diagnosis of
      polycythemia vera would be highly desirable; however, none exists. The value of
      quantization of neutrophil PRV-1 mRNA, platelet c-mpl expression, in vitro assays
      of erythroid progenitor cells, serum erythropoietin levels, establishing
      clonality in female subjects using assays employing X-chromosome-based
      polymorphism assays, and the progress in the chromosomal location of the gene is
      discussed. Integration of this information underlies the complexity of the
      molecular biology of polycythemia vera and indicates likely interaction of
      multiple genetic events in the genesis of polycythemia vera. SUMMARY: The
      existence of family clustering of PV may facilitate the search for PV molecular
      basis. Only collaborative interaction of clinical researchers and laboratory
      scientists will lead to meaningful progress in determining the molecular basis of
      PV.

PMID- 15725901
TI  - Controlling the complement system for prevention of red cell destruction.
AB  - PURPOSE OF REVIEW: Complement sensitization of red blood cells (RBCs) can lead to
      both intravascular and extravascular red cell destruction. Altered levels of
      naturally occurring complement regulatory proteins on red cells can result in
      hemolysis, while defective expression of these proteins on immune cells can cause
      breakdown of tolerance to self antigens and is associated with autoimmune
      disease. RECENT FINDINGS: To date several complement inhibitors, including
      recombinant forms of complement regulatory proteins, humanized antibodies, and
      synthetic molecules have been described that limit complement activation by
      interfering with different steps in the complement cascade. However, few have
      been evaluated for prevention of complement-mediated RBC destruction. In this
      review, possible applications of these complement inhibitors for treatment of
      complement-mediated hemolysis in specific disease states are described.
      Furthermore, the implication of the regulatory role of complement in the
      development of autoimmune hemolytic anemia is discussed. SUMMARY: Complement
      therapeutics has potential for effective and safe prophylactic use and treatment
      of hemolytic transfusion reactions and complement-mediated hemolytic diseases.
      Furthermore, the regulatory function of complement may be exploited to prevent
      and treat autoimmune hemolytic anemia.

PMID- 15725902
TI  - Anemia in older adults.
AB  - PURPOSE OF REVIEW: Anemia is common in older adults and is an independent
      predictor for increased morbidity and mortality in several disease states. Older
      persons with anemia suffer hospitalization, physical decline, and disability at
      higher rates than those people without anemia. RECENT FINDINGS: The prevalence
      and causes of anemia in community-dwelling older persons in the US were evaluated
      in the third National Health and Nutrition Examination Survey (NHANES) 1988-1994.
      In persons 65 years and older, anemia was present in 11.0% of men and 10.2% of
      women, with the prevalence rising to over 20% in people 85 years and older. One
      third of the cases were due to nutritional deficiencies, and one third was due to
      chronic illness, including but not limited to chronic kidney disease. About one
      third of the cases of anemia remain unexplained. Anemia is also prognostic for
      diminished physical performance and loss of mobility in people 65 years and
      older. A recent report suggests that the prevalence of anemia is even higher in
      elderly persons living in nursing homes. The data suggest that the risk of
      mortality and loss of mobility even extends to levels of hemoglobin normally
      considered low normal by WHO criteria, raising the question about optimal
      hemoglobin levels in the elderly. SUMMARY: Anemia is a common modifiable
      predictor of poor medical outcome in older adults and, as such, should be
      actively managed. Clinical studies are necessary to assess the effect of
      treatment of anemia on outcomes specific to the elderly, like disability.

PMID- 15725903
TI  - New developments in iron chelators.
AB  - PURPOSE OF REVIEW: For three decades, deferoxamine has been the only approved
      iron chelator. This drug has an extremely short-half life and is not orally
      absorbed; thus, a search has been ongoing for alternative chelators with less
      onerous delivery. Recently, several oral iron chelators and variations of
      deferoxamine to prolong the half-life have been developed. These and the methods
      of monitoring iron overload are the subjects of this review. RECENT FINDINGS: New
      chelators, combinations of chelators and regimens for known chelators and their
      safety and efficacy are being studied in important preclinical and clinical
      trials. SUMMARY: The care and clinical outcomes of patients with thalassemia and
      other iron-overload disorders may be markedly improved by recent discoveries and
      novel approaches to chelation therapy.

PMID- 15725904
TI  - Blood group antigens in health and disease.
AB  - PURPOSE OF REVIEW: Blood group antigens are polymorphic, inherited structures
      located on the surface of the red blood cell. They have long played an important
      role in identifying matched blood products for transfusion. Recent studies have
      identified varied and important functions for some of these molecules in cell
      physiology and human pathology. RECENT FINDINGS: Many novel functions associated
      with blood group antigens have recently been identified. These include
      contributing to erythrocyte membrane structural integrity, transport of molecules
      through the membrane, and complement regulation as well as acting as adhesion
      molecules, receptors for extracellular ligands, and enzymes. Importantly,
      deficiency of these membrane components is associated with certain red cell
      disorders. Furthermore, as the same components are expressed in a variety of non
      erythroid cells, deficiency of these proteins can also result in various other
      pathologies. SUMMARY: Novel functions for red cell membrane components carrying
      blood group antigens are being identified. These findings are providing new
      molecular insights into the pathophysiology of both red cell disorders as well as
      various related pathologies in other organ systems.

PMID- 15725905
TI  - Coagulation factor V: a plethora of anticoagulant molecules.
AB  - PURPOSE OF REVIEW: Thrombin is necessary for survival and is produced after
      activation of prothrombin by prothrombinase at the site of a vascular injury.
      While the enzyme component of prothrombinase alone, factor Xa, bound to a
      membrane surface can activate prothrombin, incorporation of the cofactor
      molecule, factor Va, into prothrombinase results in a five orders of magnitude
      increase in the catalytic efficiency of factor Xa that provides the physiologic
      pathway for thrombin generation. While the kinetic constants and the identity of
      peptide bonds cleaved in prothrombin to generate alpha-thrombin have been long
      established, the peptidyl portions of the factor Va molecule responsible for its
      interactions with factor Xa, prothrombin, and the lipid surface are still the
      subject of intense investigation. In this review, we summarize the current state
      of knowledge with respect to the interactions of the factor Va molecule with the
      various components of prothrombinase. RECENT FINDINGS: Binding sites for factor
      Xa have been identified on both the heavy and light chains of factor Va. Two
      amino acid regions that interact with factor Xa have been delineated on the heavy
      chain of the cofactor. It has also been demonstrated that the carboxyl-terminal
      portion of the heavy chain of factor Va contains hirudin-like motifs and appears
      to be responsible for the interaction of factor Va with prothrombin. This region
      of the molecule is important for procofactor activation by thrombin as well as
      cofactor function. Finally, the membrane-binding site of factor Va is contributed
      by several elements of the light chain and involves both electrostatic and
      hydrophobic interactions. SUMMARY: The absence or dysfunction of factor Va leads
      to hemorrhagic diseases while prolonged existence of the active cofactor species
      is associated with thrombosis. Thus, modulation of the incorporation of factor Va
      into prothrombinase in vivo by using synthetic peptides that have the potential
      to impair factor Va binding to any of the components of prothrombinase, will
      allow for control of the rate of thrombin generation at the site of vascular
      damage. As a consequence, a systematic definition of the regions of factor Va
      governing its incorporation within prothrombinase will provide the scaffold for
      the synthesis of potent anticoagulant molecules that could modulate thrombin
      formation and suppress excessive clotting in thrombotic individuals.

PMID- 15725906
TI  - Zebrafish: a tool to study hemostasis and thrombosis.
AB  - PURPOSE OF REVIEW: In the past eight years our laboratory has developed the
      zebrafish model to study hemostasis and thrombosis. The purpose of this review is
      to explore current developments involving the zebrafish model in the study of
      hemostasis and thrombosis because the time is now ripe to apply this model to
      identify novel players that participate in hemostasis and thrombosis. RECENT
      FINDINGS: In the past twelve months, three papers appeared in the hemostasis and
      thrombosis area using the zebrafish model. The first one is a review article that
      summarizes establishment of the zebrafish model to study hemostasis and
      thrombosis. The second study is a methodological paper describing assays for
      measuring hemostasis and thrombosis by inducing vascular occlusion in zebrafish
      larvae. The third paper describes a knockdown of prothrombin in zebrafish, which
      recapitulates knockout studies in mouse, and marks the beginning of studies in
      the hemostasis and thrombosis area by this new knockdown technology. In addition
      to the above papers, there is one abstract that describes kinetics of thrombocyte
      and thrombocyte-microparticle recruitment in laser-induced arterial thrombus
      formation in zebrafish. SUMMARY: With the above advances, the zebrafish model has
      now matured to the point that it can address more important questions in the
      hemostasis and thrombosis area using genetic approaches. This review therefore
      summarizes the issues described in the above papers along with thoughts about
      future progress of the zebrafish model as a tool to study hemostasis and
      thrombosis.

PMID- 15725909
TI  - High-dose therapy for autoimmune neurologic diseases.
AB  - PURPOSE OF REVIEW: Autoimmune neurologic diseases are being increasingly
      recognized, and treated with conventional immunosuppressive agents. Patients with
      'refractory' conditions have been treated with high-dose therapy, with or without
      autologous stem cell transplants. This paper reviews the rationale, methods, and
      recent results of high-dose therapy and the questions that it raises. RECENT
      FINDINGS: High-dose therapy has been used in progressive multiple sclerosis and
      in myasthenia gravis and autoimmune neuropathies that are refractory to
      conventional immunotherapy. A variety of methods of immune ablation have been
      used; most require hematopoietic 'rescue' with stem cell transplantation. High
      dose cyclophosphamide alone is immunoablative but not myeloablative, permitting
      the patient's endogenous stem cells to repopulate the hematopoietic/immune
      systems. The results have been highly encouraging in many but not all cases, with
      durable responses in the limited time they have been followed up. The treatments
      carry some risks and have been reserved for refractory cases until now. SUMMARY:
      High-dose therapy, without or with stem cell transplantation, is a valuable
      resource for the treatment of patients with refractory autoimmune neurologic
      diseases. It is important to define the diseases and patient characteristics
      likely to lead to benefit, to optimize the methods of treatment and to establish
      when in the patient's course to administer it. High-dose therapy may eventually
      become the standard for treatment of severe progressive autoimmune neurologic
      disorders.

PMID- 15725910
TI  - The changing face of invasive fungal infections in hematopoietic cell transplant
      recipients.
AB  - PURPOSE OF REVIEW: To review recent observations that describe changes in the
      likelihood of invasive fungal infections, shifts in types of fungal pathogens,
      and altered manifestations of fungal syndromes after hematopoietic cell
      transplantation and explore how changes in transplant practices are influencing
      these epidemiologic shifts. RECENT FINDINGS: Shifts in invasive fungal infections
      are occurring as a consequence of changes in transplant practices, including the
      intensity of conditioning regimens, new immunosuppressive therapies, new
      antineoplastic therapies administered before hematopoietic cell transplantation,
      and possibly use of mold-active agents as prophylaxis. Non-fumigatus Aspergillus
      species and other mold pathogens, such as Fusarium and zygomycosis, are assuming
      greater prominence and may be increasing. SUMMARY: Epidemiologic shifts in
      invasive fungal infections are likely co-travelers with advances in transplant
      practices. Thus, ongoing studies of epidemiologic shifts in invasive fungal
      infections are important.

PMID- 15725911
TI  - Stem cell transplantation in multiple myeloma (0, 1, or 2).
AB  - PURPOSE OF REVIEW: Autologous stem cell transplantation is now considered the
      standard of care in patients with multiple myeloma up to 65 years of age.
      Therefore, two questions have been recently addressed by cooperative groups:
      should autologous stem cell transplantation be offered to older patients, and is
      it possible to improve the results of autologous stem cell transplantation,
      especially with double autologous stem cell transplantation? The results of
      allogeneic transplantation remain disappointing, with a high transplant-related
      mortality rate, increasing the need to explore new strategies such as reduced
      intensity conditioning. RECENT FINDINGS: A randomized Italian study confirms that
      two courses of intermediate-dose melphalan supported by autologous stem cell
      transplantation is superior to standard melphalan-prednisone even in patients
      aged 65 to 70. The Intergroupe Francophone du Myelome 94 (IFM94) trial shows that
      double transplantation is superior to single transplantation, at least in
      patients with less than 90% reduction of their M-component after one transplant.
      Several studies have addressed the issue of prognostic factors in the context of
      autologous stem cell transplantation. A prospective Dutch trial confirms poor
      results with T cell-depleted allogeneic transplantation prepared by a standard
      myeloablative regimen. The Seattle group, on the other hand, reports encouraging
      preliminary data with tandem auto/mini-allotransplantation. SUMMARY: The
      available results of randomized studies are in favor of tandem autologous
      transplantation. In the near future, ongoing studies will clarify the role of
      novel agents (thalidomide and its analogs, bortezomib) in the context of
      autologous stem cell transplantation and the place of tandem auto/mini
      allotransplantation compared with tandem autologous transplantation.

PMID- 15725912
TI  - Bone marrow transplantation for lymphoma CR1.
AB  - PURPOSE OF REVIEW: Despite several reports showing the superiority of autologous
      stem cell transplantation over conventional chemotherapy in the salvage treatment
      of non-Hodgkin lymphoma, its use as part of first-line therapy in this disease is
      still controversial. The review highlights the most relevant studies on
      autologous stem cell transplantation for non-Hodgkin lymphoma at diagnosis
      published over the past year. RECENT FINDINGS: Several recent studies have shown
      that autologous stem cell transplantation may offer survival benefits in patients
      with both diffuse large cell lymphoma and follicular cell lymphoma whose
      prognostic features are poor. An advantage of autologous stem cell
      transplantation has also been documented for other non-Hodgkin lymphoma subtypes,
      in particular mantle-cell lymphoma, in which autologous stem cell transplantation
      is probably the most effective first-line option presently available.
      Nevertheless, whether autologous stem cell transplantation is definitely better
      than conventional chemotherapy is still under discussion, and the issue is still
      less clear, given the new opportunities offered by rituximab combined with
      chemotherapy. Autologous stem cell transplantation may also benefit from the
      addition of rituximab as an in vivo purging agent. Thus, large randomized trials
      are required to fully define the role of autologous stem cell transplantation in
      first-line treatment for high-risk non-Hodgkin lymphoma. Such trials should
      compare autologous stem cell transplantation with chemotherapy, both supplemented
      with rituximab, in the most frequent CD20+ lymphoma subtypes. The up-front use of
      autologous stem cell transplantation might find support from the recent
      observation that patients who do not respond to this treatment may still have a
      good chance of being rescued by reduced-intensity allogeneic transplantation.
      SUMMARY: Autologous stem cell transplantation remains a valid research strategy
      in first-line therapy and, along with new agents and nonmyeloablative allogeneic
      transplantation, may help to increase the cure rate for high-risk non-Hodgkin
      lymphoma.

PMID- 15725913
TI  - Hematopoietic cell transplantation for congenital bone marrow failure.
AB  - PURPOSE OF REVIEW: Congenital bone marrow failure is rare and multifactorial.
      This review focuses on the outcome after allogeneic hematopoietic cell
      transplantation for the treatment of these disorders, with particular emphasis on
      recent discoveries and the challenges. RECENT FINDINGS: In the treatment of
      congenital bone marrow failure disorders, the goals are to eliminate or reduce
      early and late toxicities and the risk of graft-versus-host disease. Novel
      nonmyeloablative fludarabine-based preparative regimens have demonstrated low
      risks of toxicity and acceptable engraftment rates for several congenital bone
      marrow failure disorders. Although there seems to be less early toxicity, longer
      follow-up is needed to determine late effects, especially the development of
      malignancy. T cell depletion of the bone marrow or peripheral blood, or the use
      of umbilical cord blood, has decreased the risk of graft-versus-host disease.
      Together, reduced toxicity and low rates of graft-versus-host disease have at
      least minimized the morbidity early after transplantation, with promising early
      survival. SUMMARY: With marked improvement in rates of survival after allogeneic
      hematopoietic cell transplantation for selected congenital bone marrow failure
      disorders, emphasis is now being placed on improving quality of life and reducing
      late effects. Multicenter collaborative trials will determine the best treatment
      for these rare disorders.

PMID- 15725914
TI  - Treatment of non-small cell lung cancer and targeted therapies: where are we?

PMID- 15725915
TI  - Biomarkers for prediction of sensitivity to EGFR inhibitors in non-small cell
      lung cancer.
AB  - PURPOSE OF REVIEW: Epidermal growth factor receptor (EGFR) Inhibitors have shown
      promising results in patients with advanced non-small cell lung cancers (NSCLC)
      who previously have failed on chemotherapy. Objective response is achieved in 10
      to 28% of the patients, and about 30% will achieve stable disease. A major
      problem is how to select the patients, who will benefit from treatment, and who
      will not. RECENT FINDINGS: The predictive role of EGFR protein expression
      assessed by IHC is still debated. Specific EGFR gene mutations have been
      identified associated with response to gefitinib (Iressa(R)), but seem not to be
      associated with stable disease. No studies have yet demonstrated any association
      between EGFR gene mutations and survival. In this review we describe other marker
      studies, which are associated with sensitivity to EGFR inhibitors. Increased EGFR
      gene copy number based on FISH analysis is demonstrated to be a good predictive
      marker for response, stable disease, time to progression, and survival. SUMMARY:
      EGFR/FISH seems today to be the best predictive marker for clinical benefit from
      EGFR inhibitors in NSCLC. Prospective large scale clinical studies must identify
      the most optimal paradigm for selection of patients.

PMID- 15725916
TI  - Targeted therapies and non-small cell lung cancer: methodological and conceptual
      challenge for clinical trials.
AB  - PURPOSE OF REVIEW: Targeted therapies are emerging as important drugs in the
      treatment of advanced non-small cell lung cancer (NSCLC). Within the past months,
      there have been considerable contributions to this topic. The results of several
      important clinical trials have been published. Furthermore, laboratory results
      have significantly contributed to clear out some molecular mechanisms regulating
      sensitivity or resistance to these drugs and to provide rational basis for
      further clinical studies. RECENT FINDINGS: A great part of recently published
      research on targeted agents in NSCLC regards EGFR inhibitors. Following the
      demonstration of activity of gefitinib in patients pretreated with chemotherapy,
      four large randomized trials testing the addition of gefitinib or erlotinib to
      first-line chemotherapy have been conducted, but failed to show any advantage.
      Interestingly, erlotinib has shown efficacy compared with placebo in pretreated
      patients. Mutations in the EGFR gene have shown a strong predictive role for
      sensitivity to EGFR inhibitors. A number of other targeted agents are currently
      under investigation: most of the phase II trials maintain a traditional
      methodology, with response rate as primary measure of activity. SUMMARY: Recent
      advances will lead to a rapid expansion of further studies aimed to define the
      best way to use targeted agents in NSCLC. Several methodological issues are still
      open. The proper selection of patients, the choice of the best study design and
      the most appropriate end-point for early clinical trials, and the correct
      modality to integrate these drugs with traditional chemotherapy represent the
      most challenging points that research is called to answer in the near future.

PMID- 15725917
TI  - Treatment of locally advanced non-small cell lung cancer in the elderly.
AB  - PURPOSE OF REVIEW: Non-small cell lung cancer (NSCLC) may be considered typical
      of advanced age. Most cases of NSCLC are diagnosed in the advanced or locally
      advanced stage. It has been shown that combined chemo-radiotherapy is more
      efficient than either chemotherapy alone or radiation alone, for the therapeutic
      management of localized unresectable NSCLC. However, chemo-radiotherapy, even if
      given with sequential approach, in clinical practice can be contraindicated in
      elderly patients. In fact, this patient population often present at diagnosis
      with cardiovascular and/or pulmonary comorbidities that increase the risk of
      severe side effects from chemo-radiotherapy. The present review aims at focusing
      the currently available evidences on the treatment of elderly patients affected
      by locally advanced NSCLC and at giving future perspectives on this topic. RECENT
      FINDINGS: Very few specific prospective data are available on the treatment of
      locally advanced NSCLC in the elderly. Some phase II studies suggest that low
      dose chemotherapy given concurrently with radiotherapy could be safely
      administered to this patient population. Retrospective analyses on full-dose
      sequential and concurrent chemo-radiation are to be considered globally ambiguous
      and at risk of selection bias. SUMMARY: Only specifically designed prospective
      studies will elucidate the real role and feasibility of combined chemo
      radiotherapy in the treatment of locally advanced NSCLC in the elderly. Future
      perspectives on this topic include the evaluation of alternative schedules of
      chemo-radiotherapy, innovative radiation techniques more suitable to elderly
      patients, and the introduction of new, well-tolerated, molecularly targeted
      agents combined with standard treatments.

PMID- 15725918
TI  - Chemotherapy for advanced non-small cell lung cancer patients with performance
      status 2.
AB  - PURPOSE OF REVIEW: A beneficial role for palliative chemotherapy in patients with
      advanced non-small cell lung cancer and a good performance status (ECOG 0 or 1)
      is now well established. In this article, we focus on the available literature
      for patients with a PS of 2, in whom a role for chemotherapy has yet to be
      defined. RECENT FINDINGS: In the past, the results of randomized trials of
      comparative standard platinum-based combination chemotherapy regimens have
      demonstrated inferior survival rates in PS 2 patients compared with those with PS
      0 or 1. Consequently, a general view has emerged that the side effects of
      treatment outweigh the benefits, and chemotherapy has not been recommended as a
      standard of care. Although few studies have been designed specifically for PS 2
      patients, gemcitabine, vinorelbine or taxane monotherapy, dose-attenuated
      platinum combination regimens, and epidermal growth factor receptor inhibitors
      may provide a clinical benefit with less toxicity. For example, although the
      median survival of PS 2 patients treated with best supportive care is 2-3 months,
      chemotherapy regimens are associated with median survivals ranging from 4 to 6
      months. These data provide encouragement to revisit the role of chemotherapy in
      this group of patients. SUMMARY: There is potential with cytotoxic treatment to
      improve the palliative options for PS 2 patients with advanced non-small cell
      lung cancer. Further trials designed specifically for PS 2 patients that include
      measurement of symptoms, quality of life, and survival and toxicity are required
      to define the most active but least toxic regimens.

PMID- 15725919
TI  - Treatment of malignant thymoma.
AB  - PURPOSE OF REVIEW: The present review reports findings in the field of epithelial
      tumors originating from the thymus from the past year and discusses these
      findings in the context of the literature. RECENT FINDINGS: Epithelial tumors of
      the thymus are relatively common tumors of the anterior superior mediastinum.
      Thymomas are usually slowly growing tumors, and their prognosis depends on the
      macroscopic and microscopic invasion of surrounding tissues. Thymic carcinomas
      are more aggressive and less common tumors than thymomas and have been increasing
      in frequency in recent years. Surgery is the mainstay treatment of thymic
      malignancies, and complete resection represents the best prognostic factor in
      this disease. Postoperative radiotherapy may be indicated in tumors with invasion
      of surrounding tissues, but it is controversial in early-stage thymomas.
      Combination chemotherapy has been employed in several small studies and in
      advanced disease has been demonstrated to produce a 50-80% objective response
      rate. Neoadjuvant chemotherapy or external beam radiotherapy have been used with
      success in patients with tumors that are not readily resectable. Novel
      antiproliferative systemic agents are being investigated, based on a better
      understanding of the biology of these tumors. SUMMARY: A better understanding of
      the clinical behavior of thymomas versus thymic carcinomas and systemic therapies
      targeted to biologically validated targets in these diseases will help improve
      efficacy of treatment.

PMID- 15725920
TI  - Dermoscopy for skin cancer detection.
AB  - PURPOSE OF REVIEW: The worldwide incidence of melanoma and nonmelanoma skin
      cancers is increasing alarmingly. The development of new techniques such as
      dermoscopy leads to a consequent progress in skin cancers screening. The purpose
      of this review is to highlight recent advances in dermoscopy, reviewing primary
      research articles published in the last year. RECENT FINDINGS: With the recent
      standardization of diagnostic procedures obtained by the Consensus Net Meeting on
      Dermoscopy and the definition of new melanoma-specific criteria, the efficacy in
      early melanoma diagnosis is improved. Dermoscopy is cost effective, leading to a
      decreased number of excised benign lesions, and the dermoscopic follow-up allows
      early detection of melanomas. However, the technique must be performed by experts
      in order not to miss melanomas. For this reason, instruction in dermoscopy is
      mandatory. Moreover, computer-aided diagnosis has been tested to be a valid
      support for physicians. Teledermoscopy is a new tool that allows a second expert
      opinion to manage atypical lesions. SUMMARY: Dermoscopy opens up a new dimension
      on clinical morphology of skin lesions. Digital follow-up examinations, computer
      aided diagnosis, and teledermoscopy are new facilities that will change the
      current management of skin cancers in general and melanoma in particular.
      Dermoscopy in the hands of experienced physicians has higher discriminatory power
      than naked-eye examination to detect skin cancers.

PMID- 15725921
TI  - Clinical applications of fluorodeoxyglucose--positron emission tomography in the
      management of malignant melanoma.
AB  - PURPOSE OF REVIEW: Malignant melanoma is the seventh most common newly diagnosed
      cancer among Americans. In most cases, melanoma is curable by means of surgical
      excision if diagnosed in early stages of the disease. The prognosis is linked
      directly to the initial stage at the time of diagnosis. Early diagnosis and
      accurate disease staging is important for appropriate treatment planning. This
      review focuses on clinical applications of positron emission tomography (PET)
      using F-fluorodeoxyglucose (FDG) in the management of patients with malignant
      melanoma. RECENT FINDINGS: Many investigators have studied the role of FDG-PET in
      the management of malignant melanoma. PET has been shown to have a strong role in
      detection of metastatic disease. FDG-PET can highlight metastases at unusual
      sites that are easily missed with conventional imaging modalities. It is more
      sensitive than computed tomography (CT) for detection of metastatic lesions in
      skin, lymph nodes, and abdomen. Despite the overall superiority of FDG-PET in the
      detection of melanoma metastases, it has limitations in detection of early-stage
      disease (stage I-II), small lung nodules, and brain metastases. Most of the false
      negative FDG-PET results are due to micrometastases and lesions small than 10 mm.
      False-positive FDG-PET results are due to postsurgical inflammation, other
      inflammatory lesions, and some benign tumors. SUMMARY: FDG-PET is a metabolic,
      noninvasive imaging modality for detecting distant metastatic and recurrent
      melanoma. FDG-PET is of limited use in patients with early-stage disease and
      cannot replace sentinel node biopsy, which is much more sensitive in detecting
      microscopic lymph node metastases.

PMID- 15725922
TI  - Basal cell nevus syndrome.
AB  - PURPOSE OF REVIEW: Basal cell nevus syndrome (BCNS), is a hereditary condition
      transmitted as an autosomal dominant trait exhibiting high penetrance and
      variable expressivity. Inherited or spontaneous mutations in the human homologue
      of the Drosophila patched gene underlie the disorder and in addition to tumor
      predisposition, are associated with a range of 'patterning' defects. Recent
      advances, with glimpses of possible therapies are emerging, but because of the
      wide-ranging nature of phenotypic expression and overlap with other syndromes,
      there is difficulty. Finally, because of the importance of PTCH and paralogous
      genes in many species other than humans, reports appear in a correspondingly wide
      range of journals, which makes 'keeping abreast' difficult. RECENT FINDINGS:
      Progress has been achieved in understanding the role of Gli-1, 2, & 3 in
      development of 'sporadic' BCCs and BCNS. Expression of PTCH1 is now known to be
      regulated by alternative promoters and a single functional Gli-binding site.
      Expression of FOXE1 as a new transcriptional target of Gli2 has been demonstrated
      in human epidermis and BCCs. Finally, the discovery of Shh pathway inhibitors
      such as cyclopamine, a naturally occurring alkaloid and ornithine decarboxylase
      inhibition suggest possible interventional therapies. SUMMARY: In BCNS, phenotype
      does not correlate with position of mutations within Patched, suggesting genetic
      makeup and environment modulate effects of premature protein truncation induced
      by PTCH mutation. These developmental abnormalities occur as a result of haplo
      insufficiency in heterozygotes for the mutated gene, whereas neoplastic
      complications arise from a classical two-hit tumor suppressor gene model.
      Attention is therefore turning toward TP53 and PTCH associations.

PMID- 15725924
TI  - Bibliography. Current world literature. Transplantation.

PMID- 15725923
TI  - Biomarkers for melanoma.
AB  - PURPOSE OF REVIEW: Given the capricious nature of melanoma, biomarkers that
      provide significant insight into the behavior of melanoma would greatly aid in
      identifying patients at risk for disease progression, those whose disease has
      progressed subclinically, and those who would benefit from currently available
      systemic therapies. This review focuses on molecular prognostic markers in
      primary melanoma, markers that aid in the detection of metastatic melanoma, and
      markers predictive of systemic therapy. RECENT FINDINGS: Significant advances
      have been made in the field of melanoma biomarkers. Utilization of paraffin
      embedded tissue and multiple markers have improved the RT-PCR assays for
      detection of melanoma cells in lymph node tissue as well as peripheral blood.
      Lymphangiogenesis has been identified as a novel mechanism for melanoma
      progression, and candidate markers in the NF-kappaB signaling pathway have been
      identified to play a key role in melanoma: tumor vasculature interactions. Loss
      of heterozygosity has been used to identify potential candidates for
      biochemotherapy. Furthermore, serum S100B protein has been shown to be superior
      to lactate dehydrogenase in predicting prognosis and response to treatment for
      patients with advanced melanoma. SUMMARY: Although recent studies have
      contributed greatly to the development of melanoma markers, it is anticipated
      that the application of gene expression profiling and proteomics techniques to
      melanocytic neoplasms will result in the identification of even more effective
      biomarkers for melanoma than those currently in clinical use.

PMID- 15725926
TI  - Pelvic lymph node dissection in prostate cancer: editorial review.

PMID- 15725927
TI  - Laparoscopic adrenalectomy and adrenal-preserving surgery.
AB  - PURPOSE OF REVIEW: The aim of this paper is to define the current role of
      laparoscopy in the management of surgical adrenal diseases evaluating the
      surgical aspects, the indications and contraindications of laparoscopic
      adrenalectomy, focusing also on the most innovative tendencies in the
      laparoscopic adrenal-preserving surgery. RECENT FINDINGS: Recent publications
      have described some interesting new indications that need to be confirmed by long
      term follow up. The present review mainly focuses on defining the state of the
      art of current adrenal laparoscopic surgery. SUMMARY: Laparoscopic adrenalectomy
      is becoming the 'platinum standard' for the treatment of the adrenal surgical
      diseases and it should be considered the treatment of choice for benign adrenal
      diseases. In cases of malignancy and conservative surgery, adrenalectomy appears
      to be very promising, although a longer follow up and further studies are still
      needed to accurately assess the role played by these procedures. Finally, who
      should do laparoscopic adrenalectomy? Every patient who requires the ablation of
      the adrenal should receive laparoscopic opportunity. And the surgeons? Only those
      with advanced laparoscopic skills and a good knowledge of adrenal anatomy and
      pathophysiology will obtain the same excellent results currently reported in the
      literature.

PMID- 15725929
TI  - Laparoscopic radical prostatectomy: the learning curve.
AB  - PURPOSE OF REVIEW: Laparoscopic radical prostatectomy is now an accepted
      treatment option for the management of localized prostate cancer. Numerous
      studies have demonstrated the feasibility and the reproducibility of this
      procedure. Expert teams in high-volume centres routinely carry out laparoscopic
      radical prostatectomy but for the novice the obstacle to success is how to learn
      and gain proficiency in this procedure. In this review, we will present our views
      on how this can be done. RECENT FINDINGS: A learning curve includes the necessity
      for continuous self-evaluation in terms of cancer control, continence and
      potency. Many different methods can be used to acquire the technique: dry lab,
      animal live lab, cadaveric laparoscopic dissection or mentoring with an expert.
      All of these steps may not be essential as laparoscopic radical prostatectomy is
      not too dissimilar to open prostatectomy. However, one must understand that the
      physiological consequences of anaesthesia during laparoscopy and basic
      laparoscopic suturing technique should be perfected prior to taking on
      laparoscopic radical prostatectomy. The training then must continue under the
      supervision of a mentor. The opportunity for discussion with an expert allows the
      novice to learn the pitfalls and the tips and tricks of laparoscopic radical
      prostatectomy, thus reducing the length of the learning curve and negating the
      need to reinvent the wheel. SUMMARY: Laparoscopic radical prostatectomy is
      similar to any other new surgical procedure and as with open surgery we learn and
      gain experience with each procedure; the learning curve is never completely
      finished.

PMID- 15725928
TI  - Laparoscopic radical nephrectomy for renal cell carcinoma: the standard of care
      already?
AB  - PURPOSE OF REVIEW: Laparoscopic radical nephrectomy has been developed and
      applied for patients with renal cell carcinoma since 1992. The number of patients
      undergoing laparoscopic radical nephrectomy has increased explosively worldwide
      in recent years, and laparoscopy is now extended to patients with advanced
      disease. It is very important to clarify the present status of laparoscopic
      radical nephrectomy among the treatment modalities for patients with renal cell
      carcinoma. RECENT FINDINGS: Laparoscopic radical nephrectomy has a minimally
      invasive nature as well as comparable long-term cancer control in patients with
      pT1-3a renal cell carcinoma to open surgery. It is technically applicable for N1
      2 disease and T3b disease if the tumor thrombus is within the renal vein. Also,
      it is feasible as a cytoreductive surgery for patients with M1 disease. SUMMARY:
      Laparoscopic radical nephrectomy is a standard treatment modality for T1-3a renal
      cell carcinoma patients. It is also available for treating patients with N1-2
      disease, and for patients with M1 disease as a cytoreductive surgery.

PMID- 15725930
TI  - Laparoscopic radical prostatectomy: transperitoneal versus retroperitoneal
      approach: is there an advantage for the patient?
AB  - PURPOSE OF REVIEW: Radical prostatectomy is the standard treatment for localized
      prostate cancer; its translation to a laparoscopic approach is considered today
      not only as feasible and reproducible but also as a valid and teachable
      alternative to its open counterpart. Beyond the "classical" transperitoneal
      antegrade route codified by the Montsouris group, several extraperitoneal
      approaches were developed, claiming clinical equivalence and reduced risks of
      morbidity and operative times. This article summarizes various aspects of
      different approaches and their outcome. RECENT FINDINGS: Complications reported
      about transperitoneal procedures definitely further the discovery or learning
      curves of the pioneering teams; the groups who developed extraperitoneal
      alternatives established their "new approaches" on a solid base of technical
      skills, acquired transperitoneally. Beyond the unsurpassed qualities of visual
      and working spaces belonging to the transperitoneal route, which should be taken
      into account with respect to teaching, transperitoneal antegrade approach to the
      prostate enables the surgeon with early hemostatic control and essential tactical
      choices to achieve negative surgical margins. SUMMARY: So far, as oncological and
      functional results of both approaches seem equivalent, both approaches should be
      further developed and remain available for teaching purposes. The true benefit
      for patients lies more in global quality control of surgery than in an
      obsessional search for alternatives to established techniques that have already
      stood the proof of time.

PMID- 15725931
TI  - Ureteroscopic management of upper urinary tract transitional cell carcinoma.
AB  - PURPOSE OF REVIEW: Traditionally, nephroureterectomy has been the treatment of
      choice for transitional cell carcinoma of the upper urinary tract. In an effort
      to preserve renal function, conservative therapy has evolved from complex open
      surgery to minimally invasive ureteroscopic therapy. Considering the relatively
      recent emergence of ureteroscopic therapy, a review of technical considerations
      and treatment outcome is timely. RECENT FINDINGS: There is emerging evidence that
      ureteroscopic treatment of low grade upper tract lesions provides an acceptable
      oncologic result while preserving functioning renal parenchyma. In patients with
      low grade upper tract urothelial lesions, progression is rarely reported.
      Ureteroscopy has for over a decade been the premier diagnostic tool, with the
      actively deflectable flexible instrument being employed to map the entire
      intrarenal collecting system. Improvements in instrumentation and refinement in
      technique have broadened the application of the ureteroscope in treating upper
      urinary tract urothelial tumors. SUMMARY: For low grade lesions, which make up
      more than 50% of all presentations, ureteroscopic management has proven
      efficacious. As with similar grade lesions in the bladder, these patients require
      careful, consistent, and often lifelong follow up as many will develop recurrent
      lesions throughout the urothelium. Here too, ureteroscopy has a central role in
      surveillance.

PMID- 15725932
TI  - Bipolar electrosurgery for benign prostatic hyperplasia: transurethral
      electrovaporization and resection of the prostate.
AB  - PURPOSE OF REVIEW: The gold standard for surgical treatment of benign prostatic
      hyperplasia continues to be transurethral resection of the prostate, which is
      traditionally performed using a monopolar electrocautery system resulting in the
      possibility of certain well-recognized complications. This has led to the
      development of alternative surgical procedures such as vaporization of the
      prostate and most recently use of bipolar systems. The advantages of bipolar
      electrosurgery include the ability to use isotonic saline during surgery, reduced
      blood loss and less heat damage to the surrounding tissue. We have reviewed some
      of the technical aspects of the bipolar systems as well as their clinical use.
      RECENT FINDINGS: Bipolar electrovaporization of the prostate (Gyrus Medical Ltd,
      Cardiff, Wales) has been established for a few years and some data are available
      suggesting that the system is safe and effective, at least in the short term. The
      new technique of bipolar transurethral resection of the prostate has been studied
      in a small number of studies with promising results. SUMMARY: Bipolar
      transurethral resection is a novel approach in treatment of the prostate. A real
      paucity of clinical data is seen regarding the outcomes with this form of
      surgery. Although the generator and the resecting loop are different to the
      monopolar system, the resection technique is very similar which may be attractive
      to practising urologists. The need for large multi-centre studies in
      effectiveness of bipolar transurethral resection of the prostate is apparent.

PMID- 15725933
TI  - Endoscopic stone surgery: minimizing the risk of post-operative sepsis.
AB  - PURPOSE OF REVIEW: Urosepsis from manipulation of the urinary tract during stone
      surgery can be catastrophic despite antibiotic prophylaxis and sterile pre
      operative urine. We have reviewed recent literature with regards to pathogenesis,
      predictors of infected stones and prevention of urosepsis. RECENT FINDINGS:
      Bladder urine culture has been found to correlate poorly with infection in the
      upper urinary tract, defined by either stone or pelvic urine culture. This
      specimen, which has been the cornerstone in pre-operative preparation of
      patients, does not predict urosepsis. Authors recommending routine stone culture
      found that the presence of infected stones is highly predictive of potential
      sepsis. Terminology for systemic infection has been standardized and used in
      recent literature to define urosepsis. SUMMARY: Recent studies have recommended
      changes in the approach to the peri-operative management of stone surgery.
      Predictors of potential sepsis have also been identified.

PMID- 15725934
TI  - Endoscopic management of stones in children.
AB  - PURPOSE OF REVIEW: Management of pediatric urolithiasis has evolved from open
      surgery to minimally invasive techniques. With advancements in instrumentation,
      endourological procedures are being performed more commonly in children. The
      current article reviews the literature published from January 2003 to September
      2004 regarding endoscopic management of stones in children. RECENT FINDINGS:
      Whereas recent literature supports shock-wave lithotripsy as the preferred
      treatment option for pediatric stones, it also confirms the safety of
      percutaneous nephrolithotomy and ureteroscopy in all age groups. Retrograde
      intrarenal surgery and laparoscopic surgery are newer additions to the
      armamentarium of the endourologist but their role needs to be better defined.
      SUMMARY: The majority of stones in children can be managed using minimally
      invasive techniques. Proper treatment planning and use of appropriate
      instrumentation are important to achieve optimal outcome.

PMID- 15725935
TI  - Urolithiasis and obesity: metabolic and technical considerations.
AB  - PURPOSE OF REVIEW: The increasing prevalence of obesity poses a challenge to
      urologists in the diagnosis and treatment of urolithiasis. This review summarizes
      the new evidence linking obesity and urolithiasis, and the technical
      considerations and modifications necessary in the diagnosis and treatment of
      stone disease in obese patients. RECENT FINDINGS: Recent studies have confirmed
      the epidemiological link between obesity and urolithiasis, and have provided some
      possible explanations for its underlying cause. New clinical series have
      demonstrated that flexible ureterorenoscopy and adapted percutaneous
      nephrolithotomy techniques can result in similar stone clearance rates and
      morbidity to the non-obese patient. New data, however, suggest that obesity may
      be an independent predictor of extracorporeal shock wave lithotripsy treatment
      failure for ureteric stones. Evidence of the efficacy of dietary modification and
      medical treatment of metabolic abnormalities has been reported in obese stone
      formers. SUMMARY: Urolithiasis can be safely and effectively managed in obese
      patients with minor modifications to the established surgical techniques.
      Increased understanding of the underlying metabolic abnormalities in obese
      patients with urolithiasis may improve prevention strategies in the future.

PMID- 15725937
TI  - How significant are clinically insignificant residual fragments following
      lithotripsy?
AB  - PURPOSE OF REVIEW: Extracorporeal shock-wave lithotripsy had revolutionized the
      treatment of kidney stones. Residual fragments smaller than 4 or 5 mm which are
      asymptomatic and likely to pass spontaneously are termed as clinically
      insignificant residual fragments. This article reviews the current literature
      with regards to the management of clinically insignificant residual fragments.
      RECENT FINDINGS: However, the term is controversial because no consensus has been
      reached regarding its exact definition or interval after extracorporeal shock
      wave lithotripsy to evaluate its presence. While most small residual stone
      fragments might be managed expectantly, a significant number of patients might
      become symptomatic or require intervention. These so-called clinically
      insignificant residual fragments have the potential to cause obstruction and are
      important risk factors for stone recurrence and re-growth. SUMMARY: Residual
      fragments require close monitoring for stone growth, potential complications and
      subsequent intervention. Secondary procedures may be applied selectively to those
      patients who have significant symptoms of obstruction associated with the
      residual stone. Medical therapy might play an important role in the management of
      residual fragments.

PMID- 15725936
TI  - Developments in stone prevention.
AB  - PURPOSE OF REVIEW: This review focuses on new developments in stone prevention.
      Unfortunately, no major progress in this field has happened. There is a worldwide
      lack of randomized and controlled trials, which could confirm our theoretical
      assumptions and preventive concepts in stone disease. With these preconditions in
      mind, this review presents the current knowledge of metabolic influences causing
      the symptom "stone" and the effective measures against it. RECENT FINDINGS:
      Modern lifestyle, dietary habits and obesity emerge to be the promoters of
      idiopathic stone disease. Cross-sectional studies showed significant correlations
      between these factors and kidney stones with direct implications on our
      preventive concepts: normalization of body mass index, adequate physical
      activity, balanced nutrition and sufficient circadian fluid intake. Modern diets
      containing a lot of animal protein, refined carbohydrates and salt act on the
      metabolism like an acid load. To overcome these disadvantageous effects, a
      sufficient supply of potassium and alkali is required. Last but not least,
      calcium should not be restricted. There is clear evidence from clinical and
      experimental research that a normal or a high calcium supply is appropriate in
      calcium stone disease. Only in absorptive hypercalciuria calcium restriction
      remains beneficial in combination with thiazide and citrate therapy. SUMMARY: Up
      to 85% of all stone patients could anticipate lower risk of stone recurrence with
      elementary reorientation of their lifestyle and dietary habits. Normalizing the
      major risk factors is easy and cheap. About 15% of patients forming stones
      require additional specific pharmacological prevention. The specific measures to
      avoid recurrence of the stone disease are precisely defined.

PMID- 15725938
TI  - Artificial neural networks in urolithiasis.
AB  - PURPOSE OF REVIEW: The management of urolithiasis is a clinical challenge
      worldwide which may result in difficulty in diagnosis, treatment and prevention
      of recurrence. Artificial neural networks (ANNs) are well described adjuncts to
      many aspects of clinical urological practice. We review literature published in
      on-line Medline-citable English language journals to assess whether ANNs are
      useful in clinician-led decision-making processes in urolithiasis. RECENT
      FINDINGS: Studies have examined the role of ANNs in prediction of stone presence
      and composition, spontaneous passage, clearance and regrowth after treatment.
      These reports suggest that ANNs can identify important predictive variables and
      accurately predict treatment outcome. SUMMARY: Although well described in general
      urological practice, there is comparatively little research into the role of ANNs
      in urolithiasis. Initial results appear promising; however, further prospective
      studies are necessary to determine if this mode of analysis is superior to
      standard statistical predictive methods.

PMID- 15725939
TI  - Bibliography. Current world literature. Minimally invasive surgery in urology.

PMID- 15725942
TI  - Evidence for sodium azide as an artifact mediating the modulation of inducible
      nitric oxide synthase by C-reactive protein.
AB  - C-reactive protein (CRP) is an acute-phase protein identified as a cardiovascular
      risk marker. In recent years, an increasing number of studies have investigated
      the possible direct effects of CRP on the vasculature, using mainly commercial
      CRP. In the present work, a potential role for CRP as a modulator of inducible
      nitric oxide synthase (iNOS) induction was explored. Cultured human aortic
      vascular smooth muscle cells (HASMC) were stimulated for 18 hours with 10 ng/mL
      interleukin-1beta (IL-1beta), resulting in a marked increase of iNOS levels and
      NO production, as determined by Western blotting and nitrite measurement,
      respectively. Commercial CRP (1 to 100 microg/mL) concentration-dependently
      inhibited the effects elicited by IL-1beta. Unexpectedly, similar results were
      observed when the commercial CRP solution was replaced by the corresponding
      vehicle medium containing growing concentrations of sodium azide. The inhibitory
      effects of commercial CRP or vehicle medium were lost on sodium azide removal by
      dialysis. In conclusion, sodium azide from the commercial CRP solution, but not
      CRP itself, mainly accounts for the inhibitory effect on IL-1beta-evoked iNOS
      induction and NO release. Care should be taken before attributing any biologic
      role to commercial CRP containing sodium azide.

PMID- 15725943
TI  - Effect of saline load and metoclopramide on the renal dopaminergic system in
      patients with heart failure and healthy controls.
AB  - Dopamine of renal origin has natriuretic/diuretic actions by activating D1-like
      receptors of the nephron. Saline load increases renal dopamine production and
      natriuresis in healthy subjects, and, under these conditions, the activation of
      D2-like receptors also produces natriuresis/diuresis. Metoclopramide is a D2-like
      receptor antagonist. Patients with heart failure (HF) have an increased renal
      dopamine-synthesizing efficiency. However, the effect of salt loading was not
      explored in HF. We hypothesized that HF patients respond to salt loading with
      increased production of renal dopamine and that metoclopramide antagonizes this
      response. This was a randomized, controlled, crossover study exploring the effect
      of NaCl and metoclopramide on renal dopaminergic, sympathetic, renin-angiotensin
      aldosterone, and arginine-vasopressin (AVP) systems activity on sodium handling
      in 9 HF patients and 9 controls. NaCl markedly increased renal dopamine
      production and natriuresis in both groups. Metoclopramide blunted these responses
      in HF patients but not in controls. NaCl decreased renin and aldosterone plasma
      levels in controls but not in HF patients. In these patients B-type natriuretic
      peptide (BNP) levels increased, but AVP was not affected. HF patients respond to
      salt loading with increased natriuresis. However, the mechanisms for this
      response are different from those found in healthy subjects. Metoclopramide has
      antinatriuretic effects only in HF patients.

PMID- 15725944
TI  - Behavior of caveolae and caveolin-3 during the development of myocyte
      hypertrophy.
AB  - Recent studies have indicated that caveolae are enriched in a variety of
      signaling molecules, some of which are associated with cardiomyocyte hypertrophy.
      Caveolin-3, a major constituent of cardiac caveolae, has been suggested to
      interact with several signaling molecules. We investigated the morphologic
      changes of caveolae and caveolin-3 expression in hypertrophied cardiomyocytes
      induced by an alpha1-adrenergic agonist. Cultured rat neonatal cardiomyocytes
      were used for the experiments. Phenylephrine induced cellular hypertrophy
      associated with an increase of the number of caveolae and an up-regulation of
      caveolin-3. Although PMA increased the number of caveolae and the caveolin-3
      expression, the extent of these up-regulations was less than that by
      phenylephrine. Moreover, ionomycin increased the number of caveolae and up
      regulated caveolin-3 as much as phenylephrine. Phenylephrine-induced up
      regulations of caveolae and caveolin-3 expression were inhibited by BAPTA,
      suggesting that the intracellular Ca2+ is involved in those regulations.
      Inhibitors of calcineurin and Ca2+calmodulin-dependent kinase II attenuated the
      phenylephrine-induced up-regulation of caveolin-3. In pressure-overloaded rat
      hearts, caveolin-3 protein levels were increased compared with sham-operated
      rats. In conclusion, the number of caveolae and the expression of caveolin-3 were
      up-regulated in rat hypertrophied cardiomyocytes, possibly via the alterations of
      intracellular Ca2+ and protein kinase C.

PMID- 15725945
TI  - Nitroglycerin improves left ventricular relaxation by changing systolic loading
      sequence in patients with excessive arterial load.
AB  - Nitroglycerin abbreviates left ventricular (LV) relaxation through improved
      hemodynamics as well as by direct actions on the myocardium. The aim of this
      study was to examine whether the changing systolic loading sequence during
      nitroglycerin administration affects LV relaxation in patients with excessive
      arterial load. By use of a conductance catheter with microtip manometer, the
      effects of intravenous nitroglycerin (0.3-0.5 microg/kg/min) on LV function and
      hemodynamics were examined in 39 patients with various degrees of LV
      contractility. Patients were divided into two groups according to LV-arterial
      coupling, the ratio of end-systolic elastance (Ees) to effective arterial
      elastance (Ea). In patients with Ees/Ea ratio > 1, nitroglycerin had no effect on
      the time to peak force or on the time constant of LV relaxation (tau). On the
      other hand, in patients with Ees/Ea < 1, which represented excessive arterial
      load, nitroglycerin significantly shortened the time to peak force, shifted the
      peak of the loading sequence from late to early systole, and significantly
      decreased tau without any changes in Ees. Thus, nitroglycerin improved LV
      relaxation in patients with excessive arterial load partly by changing the
      systolic loading sequence.

PMID- 15725946
TI  - Estrogen protects cardiac myogenic (H9c2) rat cells against lethal heat shock
      induced cell injury: modulation of estrogen receptor alpha, glucocorticoid
      receptors, heat shock protein 70, and iNOS.
AB  - In the present study we have established that exposure of rat cardiac myoblasts
      (H9c2 cells) to 46 degrees C for 1 hour (lethal heat shock) resulted in optimal
      cell injury as determined by lactate dehydrogenase release. Pretreatment of H9c2
      cells for 24 hours with 17beta-estradiol significantly protects myoblasts against
      subsequent lethal heat shock exposure in a concentration-dependent manner with
      maximum protection obtained at 1 microM of 17beta-estradiol. With Western
      blotting, it was observed that 17beta-estradiol-protected cells had significantly
      higher levels of the estrogen receptor alpha and inducible heat shock protein 70
      (hsp70) as well as inducible nitric oxide synthase (iNOS) levels compared with
      lethal heat shock-exposed cells. In contrast, lethal heat shock-exposed cells had
      significantly higher levels of total cellular glucocorticoid receptors (GR), both
      cytoplasmic and nuclear, compared with 17beta-estradiol-protected cells.
      Immunofluorescence technique using confocal microscopy revealed nuclear
      localization of the glucocorticoid receptors (GR) in lethal heat shock-exposed
      H9c2 cells while 17beta-estradiol-protected cells had primarily extranuclear
      localization of GR. We conclude that (1) 17beta-estradiol protects H9c2 cells
      against lethal heat shock insult by a receptor-independent mechanism, and (2) the
      protective effects are likely mediated by modulation of GR, hsp 70, and iNOS
      expression.

PMID- 15725947
TI  - Endothelial NOS-mediated relaxations of isolated thoracic aorta of the C57BL/6J
      mouse: a methodological study.
AB  - Endothelium-dependent relaxations were studied in the thoracic aorta (TA) of the
      C57BL/6J mouse, a strain used commonly in the generation of genetically altered
      mice, to clarify some methodological questions. First, we have tested if
      transcardial perfusion with heparinized Krebs solution before the preparation of
      the TA may improve in vitro relaxant responses. Carbachol, thrombin, and ATP
      induced significantly stronger relaxations in TAs prepared from perfused animals
      than in controls. The effect of sodium nitroprusside (SNP), however, did not
      change, indicating that the improvement of the endothelium-dependent relaxations
      after perfusion was not caused by increased reactivity of the vascular smooth
      muscle to NO. Second, the potential regional differences within the TA were
      studied. Carbachol relaxed significantly stronger distal than proximal TA
      segments, whereas the effects of thrombin, ATP, and SNP showed no regional
      heterogeneity. Third, the relaxant effect of carbachol was partially preserved in
      TAs of endothelial NOS deficient (eNOS-/-) animals and remained unchanged in the
      presence of indomethacin, indicating the involvement of an eNOS- and
      cyclooxygenase-independent mechanism in the mediation of the response. Thrombin
      and ATP were ineffective in eNOS-/- TAs. Finally, TAs prepared from mice housed
      in cages equipped with running wheels did not show improved reactivity,
      indicating that the conventional housing conditions and the consequent sedentary
      lifestyle of the laboratory mouse do not diminish endothelial function in the TA.

PMID- 15725948
TI  - The vasorelaxing action of labedipinedilol-A involves endothelial cell-derived NO
      and eNOS expression caused by calcium influx.
AB  - Labedipinedilol-A, a novel dihydropyridine-type calcium antagonist, has been
      shown to induce hypotension and vasorelaxation. The objective of the present
      study was to investigate the effect of labedipinedilol-A on vascular function of
      rat aortic rings and cultured human umbilical vein endothelial cells (HUVECs).
      Labedipinedilol-A induced vasorelaxation in rat aortic rings that had been
      precontracted with phenylephrine in a concentration-dependent manner. This
      labedipinedilol-A-induced relaxation was significantly reduced by endothelium
      removal and by exposure to L-NG-nitroarginine methyl ester (L-NAME), methylene
      blue, or 1H-[1,2,4]oxadiazolol[4,3,a]quinoxalin-1-one (ODQ). In addition, the
      cyclic GMP content was significantly increased by labedipinedilol-A, which was
      inhibited by L-NAME in aorta. In cultured HUVECs, labedipinedilol-A induced
      concentration-dependent formation of NO and Ca2+ influx, and it increased the
      abundance of endothelial NO synthase (eNOS) protein. Furthermore, labedipinedilol
      A suppressed basal, 10% FBS- and thrombin-stimulated endothelin-1 production,
      which were reversed by pretreatment with L-NAME, demonstrating that NO was able
      to inhibit production of ET-1 in HUVECs. Labedipinedilol-A significantly
      protected cultured HUVECs against dihydroxyfumarate/iron ion-induced decrease of
      glutathione and cell death. Moreover, labedipinedilol-A also inhibited iron
      induced lipid peroxidation in rat brain homogenate and scavenged 2,2'-azobis (2
      amidinopropane) dihydrochloride-derived peroxy radicals. Labedipinedilol-A acts
      as lacidipine with additional antioxidant effects and can protect endothelial
      cells against free radical-induced lipid peroxidation and cell injury. Our
      results indicate that the endothelium-dependent vasorelaxation by labedipinedilol
      A is mediated through Ca2+-dependent activation of NO synthase and stimulation of
      NO/cyclic GMP pathway.

PMID- 15725949
TI  - Differential blocking action of dihydropyridine Ca2+ antagonists on a T-type Ca2+
      channel (alpha1G) expressed in Xenopus oocytes.
AB  - Recent reports show that efonidipine, a dihydropyridine Ca2+ antagonist, has
      blocking action on T-type Ca2+ channels, which may produce favorable actions on
      cardiovascular systems. However, the effects of other dihydropyridine Ca2+
      antagonists on T-type Ca2+ channels have not been investigated yet. Therefore, in
      this study, we examined the effects of dihydropyridine compounds clinically used
      for treatment of hypertension on a T-type Ca2+ channel subtype, alpha1G,
      expressed in Xenopus oocytes. These effects were compared with those on T-type
      Ca2+ channel. Rabbit L-type (alpha1Calpha2/deltabeta1a) or rat T-type (alpha1G)
      Ca2+ channel was expressed in Xenopus oocytes by injection of cRNA for each
      subunit. The Ba currents through expressed channels were measured by conventional
      2-microelectrode voltage-clamp methods. Twelve DHPs (amlodipine, barnidipine,
      benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine,
      nifedipine, nilvadipine, nimodipine, nitrendipine) and mibefradil were tested.
      Cilnidipine, felodipine, nifedipine, nilvadipine, minodipine, and nitrendipine
      had little effect on the T-type channel. The blocks by drugs at 10 microM were
      less than 10% at a holding potential of -100 mV. The remaining 6 drugs had
      blocking action on the T-type channel comparable to that on the L-type channel.
      The blocking actions were also comparable to that by mibefradil. These results
      show that many dihydropyridine Ca2+ antagonists have blocking action on the
      alpha1G channel subtype. The action of dihydropyridine Ca2+ antagonists in
      clinical treatment should be evaluated on the basis of subtype selectivity.

PMID- 15725950
TI  - Atorvastatin and myocardial reperfusion injury: new pleiotropic effect
      implicating multiple prosurvival signaling.
AB  - We investigated the potential role of atorvastatin, given at reperfusion, to
      improve survival of the ischemic/reperfused myocardium by activation of p44/42
      MAPK and p38 MAPK with its downstream effector, HSP27. We have previously shown
      that atorvastatin attenuates lethal reperfusion-induced injury via activation of
      the phosphatidyl inositol 3-kinase (PI3K) prosurvival signaling pathway. In this
      study we hypothesize that other prosurvival kinases may also be implicated in
      this protection. Langendorff-perfused mouse hearts were subjected to 35 minutes
      of global ischemia followed by 30 minutes of reperfusion, and either infarct size
      or the levels of phosphorylated AKT, p44/42 MAPK, p38 MAPK, and HSP27 were
      analyzed. Atorvastatin was administered during reperfusion only. We used
      wortmannin to block PI3K/AKT, U0126 to block p44/42 MAPK, and SB203580 to prevent
      the phosphorylation of p38 MAPK and HSP27. Atorvastatin significantly reduced
      infarct size (32.96 +/- 3.4% versus 51.27 +/- 2.79% in controls, P < 0.05). This
      protection was abrogated by wortmannin (48.38 +/- 4.28%), U0126 (52.58 +/- 7.58),
      and SB203580 (49.37 +/- 4.16%). Western blot analysis confirmed significant
      phosphorylation of AKT, p44/42 MAPK, p38 MAPK, and HSP27 following administration
      of atorvastatin during reperfusion and abrogation of the respective
      phosphorylation in the presence of their specific inhibitors. Atorvastatin given
      at reperfusion attenuates lethal reperfusion-induced injury by the
      phosphorylation of multiple prosurvival pathways involving not only PI3K/AKT but
      also p44/42 MAPK, p38 MAPK, and HSP27.

PMID- 15725951
TI  - Transregulation of the alpha2-adrenergic signal transduction pathway by chronic
      beta-blockade: a novel mechanism for decreased platelet aggregation in patients.
AB  - Platelets play a pivotal role in the pathophysiology of acute coronary syndromes.
      Chronic beta-blockade has been shown to improve the long-term clinical outcome in
      coronary heart disease. Because platelets play a central role in thrombus
      formation, the aim of the present study was to investigate if chronic beta
      blockade may transregulate the expression of alpha2-adrenergic receptors on human
      platelets and via this mechanism may modulate platelet activation. The densities
      of alpha2-adrenergic receptors of platelets were determined in healthy volunteers
      under chronic beta-blockade and as alpha2-adrenergic receptor-mediated function
      in catecholamine-induced platelet aggregation was determined. Chronic beta
      blockade induced a time-dependent reduction of alpha2-adrenergic receptors. This
      reduction was accompanied by a decrease of the alpha-subunit of Gi proteins as
      demonstrated by Western blot analysis. This transregulation at both the receptor
      level and the G-protein level resulted in an almost complete loss of the alpha2
      adrenergic receptor-mediated inhibition of adenylyl cyclase. The impairment of
      the alpha2-adrenergic receptor system correlated with a reduction of the
      catecholamine-induced activation and aggregation of human platelets. The
      functional transregulation of alpha2-adrenergic receptors by chronic beta
      blockade in platelets and the consequent impairment of platelet activation may
      contribute to the therapeutic success of beta-blocker therapy.

PMID- 15725952
TI  - Staurosporine inhibits voltage-dependent K+ current through a PKC-independent
      mechanism in isolated coronary arterial smooth muscle cells.
AB  - We examined the effects of the protein kinase C (PKC) inhibitor staurosporine
      (ST) on voltage-dependent K (KV) channels in rabbit coronary arterial smooth
      muscle cells. ST inhibited the KV current in a dose-dependent manner with a Kd
      value of 1.3 microM. The inhibition of the KV current by ST was voltage-dependent
      between -30 and +10 mV. The additive inhibition of the KV current by ST was
      voltage-dependent throughout the activation voltage range. The rate constants of
      association and dissociation of ST were 0.63 microM s and 0.92 s, respectively.
      ST produced use-dependent inhibition of the KV current. ST shifted the activation
      curve to more positive potentials but did not have any significant effect on the
      voltage dependence of the inactivation curve. ST did not have any significant
      effects on other types of K channel. Another PKC inhibitor, chelerythrine, and
      PKA inhibitor peptide (PKA-IP) had little effect on the KV current. These results
      suggest that ST interacts with KV channels that are in the closed state and that
      ST inhibits KV channels in the open state in a manner that is phosphorylation
      independent and voltage-, time-, and use-dependent.

PMID- 15725953
TI  - Direct thrombin inhibitor use during percutaneous coronary intervention.
AB  - Direct thrombin inhibitors (DTI) are emerging as alternative anticoagulants to
      unfractionated heparin and indirect thrombin inhibitors in patients undergoing
      percutaneous coronary intervention (PCI). We review the pharmacological
      properties of these newer antithrombotic agents and evaluate the clinical data
      demonstrating their use in patients undergoing PCI.

PMID- 15725954
TI  - Workshop on cancer biometrics: identifying biomarkers and surrogates of cancer in
      patients: a meeting held at the Masur Auditorium, National Institutes of Health.
AB  - The current excitement about molecular targeted therapies has driven much of the
      recent dialog in cancer diagnosis and treatment. Particularly in the biologic
      therapy of cancer, identifiable antigenic T-cell targets restricted by MHC
      molecules and the related novel stress molecules such as MICA/B and Letal allow a
      degree of precision previously unknown in cancer therapy. We have previously held
      workshops on immunologic monitoring and angiogenesis monitoring. This workshop
      was designed to discuss the state of the art in identification of biomarkers and
      surrogates of tumor in patients with cancer, with particular emphasis on assays
      within the blood and tumor. We distinguish this from immunologic monitoring in
      the sense that it is primarily a measure of the tumor burden as opposed to the
      immune response to it. Recommendations for intensive investigation and targeted
      funding to enable such strategies were developed in seven areas: genomic
      analysis; detection of molecular markers in peripheral blood and lymph node by
      tumor capture and RT-PCR; serum, plasma, and tumor proteomics; immune
      polymorphisms; high content screening using flow and imaging cytometry;
      immunohistochemistry and tissue microarrays; and assessment of immune infiltrate
      and necrosis in tumors. Concrete recommendations for current application and
      enabling further development in cancer biometrics are summarized. This will allow
      a more informed, rapid, and accurate assessment of novel cancer therapies.

PMID- 15725956
TI  - Combination of conformal radiotherapy and intratumoral injection of adoptive
      dendritic cell immunotherapy in refractory hepatoma.
AB  - A phase 1 study was conducted to assess the safety and immunologic response
      induced by direct injection of autologous immature dendritic cells (DCs) into
      tumor under radiotherapy in advanced hepatoma patients. Patients with
      advanced/metastatic stage hepatoma not suitable for surgery or transarterial
      embolization were enrolled. Groups of patients received two vaccinations. Each
      vaccination consisted of intratumoral injections of autologous immature DCs in
      four dose cohorts of 5 x 10(6), 1.5 x 10(7), 3 x 10(7), and 5 x 10(7) cells 2
      days after a single fraction of conformal radiotherapy of 8 Gy. The second
      vaccination was performed 3 weeks later. Of the 14 patients entered, 12 completed
      two cycles of vaccination. The treatment was well tolerated at any of the dose
      levels. Six patients had mild transient fever (grade 1-2) with chill reactions,
      three patients developed grade 1 fatigue, and one patient developed mild myalgia
      and arthralgia after DC injections. There was no evidence of clinically
      manifested autoimmune disease. There were two partial responses and four minor
      responses. A decrease in the alpha-fetoprotein (AFP) level of more than 50% was
      found in three patients. Ten patients had completed immunologic response
      evaluation 2 weeks after the second cycle of vaccination. The AFP-specific immune
      response was evident in eight patients examined by cytokine release assay and in
      seven patients by ELISPOT assay. Six patients showed an increased NK cell
      cytotoxic activity after vaccination. These data suggest that the combination of
      intratumoral injection of DCs and conformal radiotherapy is safe and can induce
      tumor-specific and innate immunity.

PMID- 15725958
TI  - Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome associated with
      high-dose interleukin-2 for the treatment of metastatic melanoma.
AB  - Various drugs have been associated with the development of thrombotic
      thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Among the
      biologic agents, alpha-interferon therapy, used for treatment of hepatitis B and
      chronic myelogenous leukemia, has been associated with TTP in a few recent
      reports. The authors report the first case of TTP/HUS occurring in a metastatic
      melanoma patient receiving treatment with high-dose interleukin-2 (IL-2). A 57
      year-old patient with malignant melanoma presented with seizures 3 days after
      completing the first week of high-dose IL-2, and the characteristic hematologic
      picture revealed TTP/HUS. This occurrence is unlikely to be explained by the
      association with malignant melanoma, which was not presenting with widespread
      visceral disease at the time of the occurrence, or by the use of other
      medications. Similar cytokine release profiles are encountered in TTP, HUS caused
      by Shiga toxin-1, HUS caused by E. coli O157, after IL-2 or IL-2-containing
      biochemotherapy, as well as in TTP caused by interferon-alpha. This cytokine
      profile could reflect a common cause, or just the presence of similar pathways
      involved.

PMID- 15725957
TI  - Bacterial ghosts as novel efficient targeting vehicles for DNA delivery to the
      human monocyte-derived dendritic cells.
AB  - Recombinant bacterial ghosts loaded with plasmids were tested as an antigen
      delivery system and as a potential mediator of maturation for human monocyte
      derived dendritic cells (DCs). Bacterial ghosts are cell envelopes derived from
      Gram-negative bacteria; the intracellular content is released by the controlled
      expression of plasmid-encoded lysis gene E of PhiX174. All the cell surface
      structures of the native bacteria, including the outer membrane proteins,
      adhesins, LPS, lipid A, and peptidoglycans, are preserved. Co-incubation of
      immature DCs with ghosts resulted in decreased expression of CD1a, CD80, and CD83
      molecules, while addition of maturation mix (TNF-alpha, IL-1 beta, IL-6, and
      PGE2) to the cultures enhanced expression of these molecules. No marked changes
      were observed in the expression of the CD11c, CD40, and CD86 surface molecules.
      The exposure of DCs to ghosts in combination with maturation mix resulted in a
      nonsignificant increase in their ability to activate T cells. DCs co-incubated
      with bacterial ghosts carrying plasmids encoding GFP in combination with
      maturation mix exhibited high expression levels of GFP (up to 85%). These results
      indicate that in addition to their well-established use as vaccines, bacterial
      ghosts can also be used as carriers of nucleic acid-encoded antigens.

PMID- 15725955
TI  - CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2.
AB  - CD4+CD25+ T regulatory (Treg) cells control immunologic tolerance to self
      antigens and play a role in suppressing antitumor immune responses, but the
      mechanism of suppression in vivo remains uncertain. Recently, signaling through
      the high-affinity interleukin-2 (IL-2) receptor has been shown to be critical for
      Treg cell differentiation and survival in vivo. Mice deficient in IL-2 or its
      receptor (CD25 or CD122) or deficient in downstream signaling molecules,
      including JAK-3 and STAT-5, do not develop a stable population of Treg cells and
      subsequently acquire lymphoproliferative disease and autoimmunity. in vitro, IL-2
      is required to expand Treg cells and to induce their suppressive characteristics.
      Conversely, IL-2-based regimens can activate cellular antitumor immunity and are
      the mainstay of immunotherapies directed against melanoma and kidney cancers.
      Given the seemingly disparate effects of IL-2, the authors discuss the
      possibility that IL-2 may not be the optimal T-cell growth factor in vivo, but
      rather an inducer of self-tolerance. The authors propose that other gamma c
      signaling cytokines, including IL-15, may be alternative choices for the
      immunotherapy of cancer.

PMID- 15725959
TI  - Measuring melanoma-specific cytotoxic T lymphocytes elicited by dendritic cell
      vaccines with a tumor inhibition assay in vitro.
AB  - Improving cancer vaccines depends on assays measuring elicited tumor-specific T
      cell immunity. Cytotoxic effector cells are essential for tumor clearance and are
      commonly evaluated using 51Cr release from labeled target cells after a short (4
      hours) incubation with T cells. The authors used a tumor inhibition assay (TIA)
      that assesses the capacity of cytotoxic T lymphocytes (CTLs) to control the
      survival/growth of EGFP-labeled tumor cell lines. TIA was validated using CD8+ T
      cells primed in vitro against melanoma and breast cancer cells. TIA was then used
      to assess the CTL function of cultured CD8+ T cells isolated from patients with
      metastatic melanoma who underwent vaccination with peptide-pulsed CD34+ HPCs
      derived DCs. After the DC vaccination, T cells from six of eight patients yielded
      CTLs that could inhibit the survival/growth of melanoma cells. The results of TIA
      correlated with killing of tumor cells in a standard 4-hour 51Cr release assay,
      yet TIA allowed detection of CTL activities that appeared marginal in the 51Cr
      release assay. Thus, TIA might prove valuable for measuring spontaneous and
      induced antigen-specific cytotoxic T cells.

PMID- 15725960
TI  - Boosting vaccinations with peptide-pulsed CD34+ progenitor-derived dendritic
      cells can expand long-lived melanoma peptide-specific CD8+ T cells in patients
      with metastatic melanoma.
AB  - The immunogenicity of dendritic cell (DC)-based vaccines has been shown in
      patients with advanced cancer, but it has not yet been established whether the
      elicited cancer-specific immunity is durable and whether it can be maintained by
      boosting vaccinations. The authors showed earlier, in 18 HLA-A*0201 metastatic
      melanoma patients, that four vaccinations over 6 weeks with peptide-loaded CD34
      DCs (the induction phase) expand in the blood melanoma-specific CD8+ T cells, as
      documented by melanoma peptide-specific IFN-gamma ELISPOT and cytotoxic T
      lymphocyte (CTL) activity against melanoma cell lines. The authors show here that
      the melanoma peptide-specific CD8+ T-cell immunity is short-lived, but it could
      be reactivated in 7 of 11 patients who received four boosting vaccinations with
      peptide-loaded CD34-DCs. Expansion of recall memory CD8+ T cells was confirmed by
      tetramer binding and CTL activity against melanoma peptide-pulsed T2 cells. In
      two patients boosted over 15 months, induced melanoma peptide-specific recall
      memory CD8+ T cells lasted at least 6 months. Thus, boosting vaccination with
      peptide-loaded CD34-DCs can expand long-lived tumor peptide-specific immunity.

PMID- 15725961
TI  - Diagnostic criteria for Tourette's disorder.

PMID- 15725962
TI  - Lithium, minocycline, and pseudotumor cerebri.

PMID- 15725963
TI  - Attention-deficit/hyperactivity disorder and Asperger's syndrome?

PMID- 15725964
TI  - Medication-associated somnambulism.

PMID- 15725965
TI  - Thyroxine-associated hypomania.

PMID- 15725966
TI  - Treatment guidelines for children and adolescents with bipolar disorder.
AB  - Clinicians who treat children and adolescents with bipolar disorder desperately
      need current treatment guidelines. These guidelines were developed by expert
      consensus and a review of the extant literature about the diagnosis and treatment
      of pediatric bipolar disorders. The four sections of these guidelines include
      diagnosis, comorbidity, acute treatment, and maintenance treatment. These
      guidelines are not intended to serve as an absolute standard of medical or
      psychological care but rather to serve as clinically useful guidelines for
      evaluation and treatment that can be used in the care of children and adolescents
      with bipolar disorder. These guidelines are subject to change as our evidence
      base increases and practice patterns evolve.

PMID- 15725967
TI  - Commentary: treatment guidelines for child and adolescent bipolar disorder.

PMID- 15725968
TI  - Atomoxetine treatment in children and adolescents with attention
      deficit/hyperactivity disorder and comorbid oppositional defiant disorder.
AB  - OBJECTIVE: To examine (1) moderating effects of oppositional defiant disorder
      (ODD) on attention-deficit/hyperactivity disorder (ADHD) treatment response and
      (2) responses of ODD symptoms to atomoxetine. METHOD: Children and adolescents
      (ages 8-18) with ADHD were treated for approximately 8 weeks with placebo or
      atomoxetine (fixed dosing: 0.5, 1.2, or 1.8 mg/kg/day, b.i.d.) under randomized,
      double-blind conditions. Among patients with lifetime diagnostic information (n =
      293), 39% were diagnosed with comorbid ODD and 61% were not. Treatment-group
      differences and differences between patients with and without comorbid ODD were
      examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder
      Rating Scale IV-Parent version, investigator-administered and -scored; Conners'
      Parent Rating Scale-Revised Short Form; Clinical Global Impressions Severity of
      ADHD Scale; and the parent-rated Child Health Questionnaire. RESULTS: Youths with
      ADHD and comorbid ODD showed statistically significant improvement in ADHD, ODD,
      and quality-of-life measures. Treatment response was similar in youths with and
      without ODD, except that the comorbid group showed improvement compared with
      placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day. In contrast, youths without ODD
      showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day.
      CONCLUSIONS: Atomoxetine treatment improves ADHD and ODD symptoms in youths with
      ADHD and ODD, although the comorbid group may require higher doses.

PMID- 15725969
TI  - Stimulant medication effects in a summer treatment program among young children
      with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: This study examined the effectiveness of stimulant medication on
      multiple domains of functioning in 36 young (5 to 6 years old) children diagnosed
      with attention-deficit/hyperactivity disorder (ADHD). METHOD: Five- and 6-year
      old children attending a summer treatment program between 1987 and 1997 underwent
      a randomized clinical assessment of the effect of two doses of methylphenidate
      (0.3 mg/kg versus 0.6 mg/kg) and placebo on social behavior and academic
      performance. RESULTS: Methylphenidate had an effect on all four social behaviors
      and improved two of the three areas of academic functioning. Dose effects were
      present for three of the seven dependent measures. Individual analyses indicated
      a therapeutic response rate between 39% and 100% across dependent measures.
      Furthermore, individual analyses of response indicated that across several
      important dependent measures, 39% to 98% of children showed little incremental
      improvement with the higher dose compared with the lower dose of stimulant
      medication. CONCLUSIONS: Stimulant medication is an effective treatment for young
      children diagnosed with ADHD; however, multiple domains of functioning must be
      assessed to determine the most effective dose for young children with ADHD.

PMID- 15725970
TI  - Pilot study of community-based cognitive behavioral group therapy for adolescents
      with social phobia.
AB  - OBJECTIVE: A pilot study to evaluate the efficacy of a cognitive-behavioral group
      therapy program for adolescents with social phobia, simplified both in terms of
      time and labor intensity from a previously studied program (Social Effectiveness
      Therapy for Children and Adolescents) to be more appropriate for a community
      outpatient psychiatric setting. METHOD: Twelve adolescents with social phobia
      (ages 13-18), diagnosed by DSM-IV criteria and confirmed with Anxiety Disorders
      Interview Schedule for Children assessment, were randomly assigned to treatment
      (n=6) and waitlist (n=6) groups. The waitlist group was subsequently treated, and
      results were included in the data analysis. Assessments, including Anxiety
      Disorders Interview Schedule for Children interviews and self-report Social
      Phobia and Anxiety Inventory and Beck Depression Inventory II questionnaires,
      were performed at baseline and immediately after treatment or waitlist. RESULTS:
      All subjects completed the treatment program. Compared with the waitlist group,
      treated subjects showed significantly greater improvement in both examiner
      evaluated (Anxiety Disorders Interview Schedule for Children) and self-reported
      (Social Phobia and Anxiety Inventory) symptoms of social anxiety (effect sizes
      [d], 1.63 and 0.85, respectively). No significant change was seen in Beck
      Depression Inventory II scores for treatment or waitlist groups. CONCLUSIONS:
      This study provides support for the use of simplified cognitive-behavioral
      interventions for adolescents with social phobia that are practical for community
      psychiatric settings.

PMID- 15725971
TI  - The influence of maternal stress and distress on disruptive behavior problems in
      boys.
AB  - OBJECTIVE: The current study examined how self-reported maternal stress and
      distress are associated with child disruptive behaviors. METHOD: Mother and
      teacher ratings of child disruptive behavior problems (attention problems,
      aggression, and delinquency) were collected for 215 male participants, ranging in
      age from 9 to 12 years. Participating mothers also provided self-report data on
      socioeconomic status (SES), parenting stress, and distress (depression and
      anxiety/somatization). RESULTS: Low SES was significantly associated with both
      mother- and teacher-reported child disruptive behavior problems. Regression
      analyses indicated a relation between parenting stress and mother-reported child
      disruptive behavior problems, even when controlling for SES. Results also
      indicated a significant relation between maternal distress and mother-reported
      child disruptive behavior problems (particularly attention problems), even when
      controlling for SES and parenting stress. Maternal stress and distress were not
      significantly related to teacher-reported child disruptive behavior problems.
      CONCLUSIONS: Although the lack of an association between teacher-reported
      behavior problems and maternal stress and distress could be interpreted as a
      rater bias by these mothers, it may be that the mothers' symptoms are associated
      with a stressful home environment, thus exacerbating child disruptive behavior
      problems and eventually leading to a reciprocal relation between symptomatology
      in mothers and children.

PMID- 15725972
TI  - Agreement between telephone and in-person delivery of a structured interview for
      anxiety disorders in children.
AB  - OBJECTIVE: The current study determined the viability of using the telephone to
      facilitate assessment of children using the Anxiety Disorders Interview Schedule
      for children for DSM-IV (ADIS-C-IV). METHOD: Diagnoses established during
      telephone administration of the ADIS-C-IV-Parent version were compared with
      diagnoses obtained during standard administration of the ADIS-C-IV using both
      Child and Parent versions. Seventy-three children and their parents participated
      in counterbalanced, repeated assessments. RESULTS: The level of agreement between
      telephone and standard administration for principal diagnosis (kappa=0.86),
      individual anxiety disorders (kappa=0.63-0.86), and other disorders (kappa=0.79
      0.91) were in the good to excellent range. Additionally, agreement on overall
      suitability for an anxiety treatment program was excellent (kappa=0.97).
      CONCLUSIONS: The data indicate that telephone administration of the ADIS-C-IV is
      a valid way to differentiate children who have anxiety disorders from those who
      have no disorder or other disorders, providing a less resource-demanding
      alternative to face-to-face assessment.

PMID- 15725973
TI  - Psychometric properties of the Screen for Child Anxiety Related Emotional
      Disorders (SCARED) in the general adolescent population.
AB  - OBJECTIVE: This study examined the psychometric properties of the Screen for
      Child Anxiety Related Emotional Disorders (SCARED) in a large sample of
      adolescents from the general population. METHOD: In 2001, 1,340 junior high and
      high school adolescents in the Netherlands completed the SCARED. The SCARED is a
      questionnaire that purports to measure five child and adolescent anxiety symptom
      dimensions. The factor structure of the SCARED was investigated by means of
      confirmatory factor analyses that were conducted for males and females, early (10
      13 years) and middle (14-18 years) adolescent groups, and for Dutch and ethnic
      minorities. Analyses of variance were carried out to compare mean scores for the
      various groups. RESULTS: The five-factor structure of the SCARED not only had the
      best fit for the general adolescent population but also for the age, gender, and
      ethnic groups. It was also found that the SCARED scores of the adolescent
      subgroups differed from one another in agreement with previous studies on
      adolescent anxiety disorder symptoms. CONCLUSIONS: The findings of this study
      support the claim that the SCARED has a five-factor structure. The usefulness of
      the SCARED was also demonstrated.

PMID- 15725974
TI  - Case series: outbreak of conversion disorder among amish adolescent girls.
AB  - OBJECTIVE: Outbreak investigations are challenging in a cross-cultural context,
      and outbreaks of psychiatric disease are rare in any community. We investigated a
      cluster of unexplained debilitating illness among Amish girls. METHOD: We
      reviewed the medical records of cases, consulted with health care providers,
      performed active case finding, administered open-ended and structured interviews,
      and met with Amish community members. A case-patient was defined as a resident of
      the county who was bedridden for more than 3 weeks with otherwise unexplained
      systemic weakness and anorexia from January 2000 to February 2002. RESULTS: Five
      case-patients were identified. All were Amish girls aged 9 to 13 years. All five
      had debilitating voluntary motor deficits, anorexia, and weight loss. Four
      experienced neck weakness with inability to hold up their heads. Thorough medical
      evaluations failed to identify an organic etiology. All five patients met the
      diagnostic criteria for conversion disorder. Substantial social conflict within
      the Amish community preceded illness onset. Family behavioral interventions were
      recommended. Three months after the investigation, four of five patients
      demonstrated some improvement. CONCLUSIONS: Clinicians should be aware of the
      potential for outbreaks of psychogenic illness and work to address the challenges
      of developing effective intervention strategies, particularly in the cross
      cultural context.

PMID- 15725975
TI  - A US valuation of the EQ-5D.

PMID- 15725976
TI  - Valuation of health states in the US versus the UK: two measures divided by a
      common language?

PMID- 15725977
TI  - US valuation of the EQ-5D health states: development and testing of the D1
      valuation model.
AB  - PURPOSE: The EQ-5D is a brief, multiattribute, preference-based health status
      measure. This article describes the development of a statistical model for
      generating US population-based EQ-5D preference weights. METHODS: A multistage
      probability sample was selected from the US adult civilian noninstitutional
      population. Respondents valued 13 of 243 EQ-5D health states using the time trade
      off (TTO) method. Data for 12 states were used in econometric modeling. The TTO
      valuations were linearly transformed to lie on the interval [-1, 1]. Methods were
      investigated to account for interaction effects caused by having problems in
      multiple EQ-5D dimensions. Several alternative model specifications (eg, pooled
      least squares, random effects) also were considered. A modified split-sample
      approach was used to evaluate the predictive accuracy of the models. All
      statistical analyses took into account the clustering and disproportionate
      selection probabilities inherent in our sampling design. RESULTS: Our D1 model
      for the EQ-5D included ordinal terms to capture the effect of departures from
      perfect health as well as interaction effects. A random effects specification of
      the D1 model yielded a good fit for the observed TTO data, with an overall R of
      0.38, a mean absolute error of 0.025, and 7 prediction errors exceeding 0.05 in
      absolute magnitude. CONCLUSIONS: The D1 model best predicts the values for
      observed health states. The resulting preference weight estimates represent a
      significant enhancement of the EQ-5D's utility for health status assessment and
      economic analysis in the US.

PMID- 15725978
TI  - Valuations of EQ-5D health states: are the United States and United Kingdom
      different?
AB  - PURPOSE: We sought to compare directly elicited valuations for EQ-5D health
      states between the US and UK general adult populations. METHODS: We analyzed data
      from 2 EQ-5D valuation studies where, using similar time trade-off protocols,
      values for 42 common health states were elicited from representative samples of
      the US and UK general adult populations. First, US and UK population mean
      valuations were estimated and compared for each health state. Second, random
      effect models were used to compare the US and UK valuations while adjusting for
      known predictors of EQ-5D valuations (ie, age, sex, health state descriptors) and
      to investigate whether and how the valuations differ. RESULTS: Population mean
      valuations of the 42 health states ranged from -0.38 to 0.88 for the United
      States and from -0.54 to 0.88 for the United Kingdom, with the US mean scores
      being numerically higher than the UK for 39 health states (mean difference: 0.11;
      range: -0.01 to 0.25). After adjusting for the main effects of known predictors,
      the average difference in valuations was 0.10 (P < 0.001). The magnitude of the
      difference in the US and UK valuations was not constant across EQ-5D health
      states; greater differences in valuations were present in health states
      characterized by extreme problems. CONCLUSIONS: Meaningful differences exist in
      directly elicited TTO valuations of EQ-5D health states between the US and UK
      general populations. Therefore, EQ-5D index scores generated using valuations
      from the US general population should be used for studies aiming to reflect
      health state preferences of the US general public.

PMID- 15725979
TI  - Identification of and guidance for problem drinking by general medical providers:
      results from a national survey.
AB  - BACKGROUND: Heavy alcohol use is associated with health costs and medical
      problems. There has been a growing consensus that primary care patients should be
      screened for alcohol problems. OBJECTIVES: We examined rates at which patients
      were asked about alcohol or drug use and problems, extending research in this
      area by using a standardized problem drinking instrument with a large national
      sample, examining community level variables, and assessing the extent to which
      patients who were identified received follow-up. SUBJECTS: A subsample of 7371
      persons from the 1998 Healthcare for Communities survey who reported visiting a
      general medical provider (GMP) in the past year. MEASURES: Participants completed
      questionnaires on demographics, mental and physical health, alcohol, drug use and
      problems, enrollment in a managed health care plan, whether their medical
      provider asked about alcohol or drug use, and whether they received advice,
      counseling, or referral. RESULTS: Being asked about alcohol and drug use was
      associated with being male, young, highly educated, more health problems, mental
      health diagnosis, and being classified as a problem drinker. Only 48% of problem
      drinkers received any follow-up, with most being told to "stop drinking" by their
      GMP. CONCLUSIONS: Few people are queried about alcohol or drug use when they
      visit a GMP. When problem use is identified, most patients do not receive
      appropriate follow-up and aftercare. The quality of primary care could improve if
      GMPs were educated about providing brief advice/counseling and were given
      information concerning resources in their community to make appropriate referrals
      for patients.

PMID- 15725980
TI  - Rethinking the cesarean rate: how pregnancy complications may affect
      interhospital comparisons.
AB  - BACKGROUND: The cesarean rate has served an integral role in the monitoring of
      obstetrical care, and in 2002, the national rate reached 26.1%, the highest ever
      reported. OBJECTIVE: We sought to describe the effect of clinical complications
      on hospital cesarean rates. RESEARCH DESIGN: This was a population-based cohort
      study. SUBJECTS: All laboring women without a previous cesarean who delivered in
      California in 1995 as reported through public-use hospital discharge data were
      included. MEASURES: Women with and without maternal, fetal, or placental
      complications were compared with respect to cesarean use. Using recursive
      partitioning algorithms, women with complications were stratified into clinically
      homogeneous categories, which were analyzed separately with respect to cesarean
      use. RESULTS: The 443,532 women delivered at 288 hospitals and included 116,170
      women (26.2%) in the complicated group (cesarean rate 22.6%); and 327,362 women
      (73.8%) in the uncomplicated group (cesarean rate 6.7%). At the hospital level,
      the cesarean rates among the complicated and uncomplicated patients respectively
      were: median 23.5% (range, 2.2-9.9%); and median 6.5% (range, 1.8-18.2%).
      Recursive partitioning algorithms suggested 16 distinct clinical categories, with
      cesarean rates varying from 8.9% for women with asthma to 84.5% for women with an
      unengaged fetal head. CONCLUSIONS: Cesarean rates varied widely across
      complication types, and complication-specific rates varied widely among
      hospitals. Although the presence of pregnancy complications upon hospital
      admission comprised the strongest factor affecting first-time cesarean use among
      laboring women, the importance and interdependence of these clinical conditions
      has yet to be incorporated into commonly used models for cesarean rate
      comparisons.

PMID- 15725981
TI  - Assessing the quality of preparation for posthospital care from the patient's
      perspective: the care transitions measure.
AB  - BACKGROUND: Evidence that both quality and patient safety are jeopardized for
      patients undergoing transitions across care settings continues to expand.
      Performance measurement is one potential strategy towards improving the quality
      of transitional care. A valid and reliable self-report measure of the quality of
      care transitions is needed that is both consistent with the concept of patient
      centeredness and useful for the purpose of performance measurement and quality
      improvement. OBJECTIVE: We sought to develop and test a self-report measure of
      the quality of care transitions that captures the patient's perspective and has
      demonstrated utility for quality improvement. SUBJECTS: Patients aged 18 years
      and older discharged from one of the 3 hospitals of a vertically integrated
      health system were included. RESEARCH DESIGN: Cross-sectional assessment of
      factor structure, dimensionality, and construct validity. RESULTS: The Care
      Transitions Measure (CTM), a 15-item uni-dimensional measure of the quality of
      preparation for care transitions, was found to have high internal consistency,
      reliability, and reflect 4 focus group-derived content domains. The measure was
      shown to discriminate between patients discharged from the hospital who did and
      did not have a subsequent emergency department visit or rehospitalization for
      their index condition. CTM scores were significantly different between health
      care facilities known to vary in level of system integration. CONCLUSIONS: The
      CTM not only provides meaningful, patient-centered insight into the quality of
      care transitions, but because of the association between CTM scores and
      undesirable utilization outcomes, it also provides information that may be useful
      to clinicians, hospital administrators, quality improvement entities, and third
      party payers.

PMID- 15725982
TI  - The PedsQL: reliability and validity of the short-form generic core scales and
      Asthma Module.
AB  - OBJECTIVE: We sought to assess the reliability and validity of the PedsQL 4.0
      SF15, a shortened version of the 23-item PedsQL 4.0 Generic Core Scales, which is
      a pediatric health-related quality of life (HRQoL) instrument, and the PedsQL 3.0
      SF22 Asthma Module, a short-form of the PedsQL 3.0 Asthma Module. METHODS: The
      PedsQL 4.0 SF15 and the PedsQL 3.0 SF22 Asthma Module were administered by
      telephone to 125 adolescents (aged 12-18) and 338 parents of children with asthma
      (aged 2-11). Healthy (n = 451) and chronically ill (n = 422) children, matched by
      age, respondent status, and ethnicity to the asthma sample, provided data for
      selected validity tests. RESULTS: The Total Score from the PedsQL 4.0 SF15 and
      the Asthma Symptoms scale and Treatment Problems scale from the PedsQL 3.0 SF22
      Asthma Module were sufficiently reliable for group comparisons (alpha > or = 0.70
      across all age groups) in the asthma sample. The PedsQL 4.0 SF15 and the PedsQL
      3.0 SF22 Asthma Module were able to distinguish between children of different
      clinical status and correlated as expected with measures of productivity and
      family functioning in the asthma sample. The psychometric properties of the
      PedsQL 4.0 SF15 were generally comparable to those of the original instrument.
      CONCLUSION: The Total Score of the PedsQL 4.0 SF15 and the Asthma Symptoms scale
      of the PedsQL 3.0 SF22 Asthma Module demonstrated the best reliability and
      validity and should be suitable for group-level comparisons of generic and asthma
      specific HRQoL in clinical research studies of children with asthma.

PMID- 15725983
TI  - Comparing the validity of different sources of information on emergency
      department visits: a latent class analysis.
AB  - BACKGROUND: Emergency department (ED) use in Quebec may be measured from varied
      sources, eg, patient's self-reports, hospital medical charts, and provincial
      health insurance claims databases. Determining the relative validity of each
      source is complicated because none is a gold standard. OBJECTIVE: We sought to
      compare the validity of different measures of ED use without arbitrarily assuming
      one is perfect. SUBJECTS: Data were obtained from a nursing liaison intervention
      study for frail seniors visiting EDs at 4 university-affiliated hospitals in
      Montreal. MEASURES: The number of ED visits during 2 consecutive follow-up
      periods of 1 and 4 months after baseline was obtained from patient interviews,
      from medical charts of participating hospitals, and from the provincial health
      insurance claims database. METHODS: Latent class analysis was used to estimate
      the validity of each source. The impact of the following covariates on validity
      was evaluated: hospital visited, patient's demographic/clinical characteristics,
      risk of functional decline, nursing liaison intervention, duration of recall,
      previous ED use, and previous hospitalization. RESULTS: The patient's self-report
      was found to be the least accurate (sensitivity: 70%, specificity: 88%). Claims
      databases had the greatest validity, especially after defining claims made on
      consecutive days as part of the same ED visit (sensitivity: 98%, specificity:
      98%). The validity of the medical chart was intermediate. Lower sensitivity (or
      under-reporting) on the self-report appeared to be associated with higher age,
      low comorbidity and shorter length of recall. CONCLUSION: The claims database is
      the most valid method of measuring ED use among seniors in Quebec compared with
      hospital medical charts and patient-reported use.

PMID- 15725984
TI  - Quantitative and qualitative differences between handout and mailed patient
      satisfaction surveys.
AB  - BACKGROUND: Patient satisfaction surveys are widely used to measure patients'
      opinions of the quality of the health care they have received. There are a
      variety of methods for distributing patient satisfaction surveys. Different
      distribution methods may yield significantly different satisfaction ratings.
      OBJECTIVE: We sought to compare survey ratings obtained via 2 distribution
      methods: handout versus mailed. DESIGN: Patients were randomized to receive
      either a handout survey or a mailed survey. SUBJECTS: Patients who had an
      appointment with a family practice provider in one of the regional outpatient
      centers of a large medical clinic during a 3-week period. MEASURES: An 11-item
      visit-specific patient satisfaction survey was used to survey patient
      satisfaction. RESULTS: Handout surveys yielded higher satisfaction scores than
      mailed surveys. The response rate was higher with handout surveys than with
      mailed surveys. However, handout surveys were returned with more skipped
      questions, a lower variation in ratings, and fewer written comments than the
      mailed surveys. CONCLUSIONS: Both quantitative and qualitative differences
      between the 2 distribution methods were revealed. Attempts to compare data
      obtained from the 2 different distribution methods need to be approached with
      caution.

PMID- 15725985
TI  - Quality improvement efforts and hospital performance: rates of beta-blocker
      prescription after acute myocardial infarction.
AB  - BACKGROUND: Hospitals are under increasing pressure to measure and improve
      quality of care, and substantial resources are being directed at a variety of
      quality improvement strategies; however, the evidence base supporting these
      strategies is limited. OBJECTIVE: We sought to identify quality improvement
      efforts that were associated with hospitals' beta-blocker prescription rates
      after acute myocardial infarction (AMI). RESEARCH DESIGN: This was a cross
      sectional study using data from a telephone survey of quality management
      directors at participating hospitals linked with patient-level data from the
      National Registry of Myocardial Infarction (NRMI) during the study period,
      October 1997 to September 1999. SUBJECTS: A total of 60,363 patients discharged
      with a confirmed AMI from 234 US hospitals were included. MEASURES: Hospital
      performance based on beta-blocker rates characterized as the top 20%, lower 20%,
      and middle 40% of hospitals; reported quality improvement efforts, including
      system interventions, physician leadership, administrative support for quality
      improvement efforts, and data feedback; hospital teaching status, AMI volume,
      geographic location, and ownership type. RESULTS: The mean hospital-specific beta
      blocker rate was 60.2%; however, the variation in beta-blocker use across
      hospitals was marked (range, 19.4-89.3%, standard deviation, 12.7% points), and
      quality improvement efforts used varied greatly. None of the quality improvement
      efforts distinguished higher from medium performers; the higher and the medium
      performers together were distinguished from the lower performers in
      organizational support for quality improvement efforts (fully adjusted odds ratio
      [OR] 1.89, 95% confidence interval [CI] 1.17-3.06) and physician leadership
      (fully adjusted OR 9.88, 95% CI 2.64-37.02). Among the specific quality
      improvement interventions, only standing orders were associated with having
      higher/medium versus lower performance, and their effect had borderline
      significance (fully adjusted OR 2.26, 95% CI 0.97-5.30, P = 0.07). CONCLUSIONS:
      Our findings highlight the organizational environment, specifically the absence
      of administrative support or physician leadership for quality improvement, as an
      important correlate of poor beta-blocker rates after AMI. Future studies are
      needed to isolate hospital quality improvement efforts that are associated with
      superior performance.

PMID- 15725986
TI  - Evaluation of three population-based strategies for fracture prevention: results
      of the osteoporosis population-based risk assessment (OPRA) trial.
AB  - BACKGROUND: The integration of bone density testing into well-designed fracture
      prevention programs that can be applied in populations has not been studied.
      OBJECTIVES: We sought to compare the outcomes of 3 strategies for allocating bone
      density testing within an HMO-based fracture prevention program. RESEARCH DESIGN:
      Women were randomly sampled and allocated to one of 3 groups: (1) a universal
      group, in which all were offered bone mineral density (BMD) testing (1986
      contacted; 415 participated); 2) the SCORE group, in which women scoring > or = 7
      on the SCORE questionnaire were invited for BMD testing (1940 contacted; 576
      participated); and (3) the Study of Osteoporotic Fracture (SOF)-based group, in
      which women with > or = 5 hip fracture risk factors were invited for BMD testing
      (5342 contacted; 2176 participated). SUBJECTS: Women aged 60-80 not taking
      hormone therapy or osteoporosis medication were included. MEASURES: Outcomes
      ascertained during 33 months of follow-up in all women contacted included
      initiation of osteoporosis treatment and hip and total fracture rates. Outcomes
      evaluated among all participants included changes in fracture risk factors,
      osteoporosis knowledge, and satisfaction with the program. RESULTS: Osteoporosis
      treatment rates did not differ among all women contacted but were slightly higher
      among trial participants in the universal and SCORE groups (21.1% and 20.2%,
      respectively; versus 16.7% in the SOF-based group (P value versus universal =
      0.04). Among all women contacted, fracture rates were lowest in the universal
      group (74.11/1000) and differed significantly compared with the SCORE
      (99.44/1000; P = 0.009) and SOF-based groups (91.77/1000;P = 0.02). Knowledge
      about osteoporosis risk factors was highest in the universal group and lowest in
      the SOF-based group (P < 0.01). CONCLUSIONS: The degree to which BMD testing was
      offered to women in a fracture prevention program significantly affected total
      fracture rates, change in some fracture risk factors, and knowledge about risk
      factors.

PMID- 15726011
TI  - Drugs for lipids.

PMID- 15726012
TI  - Familial occurrence of myoclonic epilepsy syndrome and acute intermittent
      porphyria.
AB  - OBJECTIVES: Myoclonic epilepsy (ME) syndrome is not rare in north-eastern Europe;
      it is also seen in various forms. Familial occurrence of ME syndrome and acute
      intermittent porphyria (AIP) was observed in three siblings. The following report
      was aimed the differentiation between co-morbidity of two different disorders or
      presence the epileptic seizures within the clinical picture of latent AIP.
      MATERIAL AND METHODS: A case report of three siblings who suffered from seizures,
      myoclonias, ataxia and minor psychological changes since the age of 8 and 9 years
      is described in the following report. RESULTS: The clinical picture most
      resembled that of "Baltic myoclonus" (dentate-rubral degeneration or dyssynergia
      cerebellaris myoclonica -- Ramsay-Hunt syndrome) with epilepsy and/or a benign
      form of progressive myoclonic epilepsy (PME). The possibility of juvenile
      myoclonic epilepsy (JME) and other aetiological factors, as less probable causes
      of ME syndrome, were considered. After 15 years of the treatment by anti
      epileptic drugs in all three siblings, AIP was discovered. CONCLUSION: Our
      interest lies in the differentiation of co-morbidity of two different disorders
      or presence of epileptic seizures as the clinical picture of latent AIP. We
      propose that the AIP attacks were caused by long-term administration of anti
      epileptic drugs. At the same time we suggest it is a coincidence that the two
      independent genetic abnormalities coexist in the subjects (benign form of
      degenerative cerebral disease and AIP).

PMID- 15726013
TI  - Clinico-hormonal correlation of oligospermic patients in the below sea level
      environment (Jordan Valley).
AB  - A correlation between serum levels of luteinizing hormone (LH), total
      testosterone (T), free T and sex-hormone binding globulin (SHBG) in normospermic
      and in oligospermic male people was done. This study was designed to measure
      serum levels of these hormones and of SHBG in people living at different altitude
      environments relative to sea level: at 209-408 meters below (the Jordan Valley,
      JV) and at 620 meters above (Irbid city, IC). In addition, a clinical awareness
      study of oligospermia was done in the North of Jordan (IC). Seminal analysis in
      287 male people (age range, 18 to 40 years old) during the period between
      12/6/1999 and 12/2/2002 showed an oligospermia of 31.4%. Serum levels of LH,
      total T, free T and SHBG in normospermic subjects in IC were similar to those in
      normospermic of the JV (3.4 +/- 1.2 vs. 4.0 +/- 1.7 MIU/ml, 19.9 +/- 4.0 vs. 20.4
      +/- 5.6 ng/ml, 53.9 +/- 15.6 vs. 47.9 +/- 10.7 pg/ml, 19.5 +/- 3.2 vs. 18.6 +/-
      2.16 nmol/l, respectively). Oligospermia was associated with increase in total T
      at both IC (27.5 +/- 4.6 vs. 19.9 +/- 4.0 ng/ml) and the JV (30.7 +/- 3.4 vs.
      20.5 +/- 5.6). The higher serum level of total T in oligospermic people in both
      IC and the JV was associated with higher levels of SHBG compared to those levels
      in normospermic subjects. On the other hand, oligospermic subjects have lower
      serum level of free T than in normospermic males (41.5 +/- 10.0 vs. 53.9 +/-
      15.6) only in IC, while in the JV, serum free T level was similar (46.5 +/- 6.1
      vs. 47.9 +/- 10.7). Taken together data for both locations, IC and the JV,
      suggest a clear correlation between total T and SHBG levels in both groups'
      normospermic and oligospermic subjects.

PMID- 15726014
TI  - Final height and growth hormone secretion after completion of growth hormone
      therapy in patients with idiopathic growth hormone deficiency and with
      abnormalities of the hypothalamic-pituitary region.
AB  - AIMS: The aim of the study was an evaluation of final height and growth hormone
      (GH) secretion after completion of GH therapy (retesting) in patients with GH
      deficiency (GHD). PATIENTS AND METHODS: The analysis comprised 53 patients (43
      boys, 10 girls) with childhood-onset GHD, who completed GH therapy and reached
      final height. Magnetic resonance imaging (MRI), performed in all the patients,
      led to the following groups: pituitary stalk interruption syndrome (PSIS),
      pituitary hypoplasia (HP), craniopharyngioma (CP) -- patients after tumour
      excision, patients with normal hypothalamic-pituitary region (NP). RESULTS: In 51
      patients, final height was normal. The height gain was significantly (p<0.05)
      greater in PSIS than in that other groups. In retesting, GH secretion was
      significantly (p<0.005) lower in PSIS and CP than in HP and in NP and also
      (p<0.05) in HP than in NP. Permanent severe GHD was confirmed in all the patients
      with PSIS and CP and in some patients with HP (37.5%), while it was excluded in
      all the patients with normal pituitary in MRI. CONCLUSIONS: It seems that in
      patients with PSIS and CP, the confirmation of persistent character of GHD needs
      no retesting, while in patients with normal MRI results, GHD diagnosis should be
      established with special attention.

PMID- 15726015
TI  - Self-mutilation in young rats after dorsal rhizotomy.
AB  - OBJECTIVES: The aim of the study was to describe the development of self
      mutilation after extensive dorsal rhizotomy of the brachial plexus performed
      during early ontogeny in rats. SETTINGS AND DESIGN: The rhizotomy was performed
      in three groups of rats according to the central nervous system maturation:
      infant, young, and adult. After the surgery the occurrence of self-mutilation
      behavior was compared. Rats from the infant group and non-mutilating
      deafferentated rats from the adult group underwent extracellular recordings from
      intralaminar thalamic neurons. Interspikes intervals of the records were compared
      by means of chaodynamic methods. RESULTS: In the infant group self-mutilation did
      not develop at all. Among the young group self-mutilation developed in 40% of
      rats and consisted of superficial wounds in all cases. In adult self-mutilation
      appeared in 80% rats and consisted of both superficial wounds (75%) and
      amputation (25%). In the newborn group and the deafferentated adult group without
      any signs of self-mutilation means of the parameters were not significantly
      different and were significantly lower than those of intact adult rats. MAIN
      FINDINGS: 1. Self-mutilation does not develop after the rhizotomy in the infant
      rats. 2. Neurons behave in chaotic way in adult as well as in young animals. 3.
      Chaodynamic parameters do not differ between infant and adult rats without any
      signs of self-mutilation. CONCLUSIONS: The results suggest that development of
      self-mutilation behavior in rats strongly depends on the ontogenetical period of
      nervous system injury, and that mature nervous system is required for the
      development of described pathological behavior.

PMID- 15726016
TI  - The main effect of cocaine- and amphetamine-regulated transcript (CART) peptide
      on hypothalamic neuronal activity depends on the nutritional state of rats.
AB  - OBJECTIVES: The anorectic and catabolic action of CART is primarily mediated by
      the hypothalamus. The study proved the hypothesis that neurons of the
      hypothalamic regulatory system of body weight differentially react to CART in
      dependence of the nutritional state of the animal: overweight, fed or short-term
      fasting. DESIGN AND SETTING: Single unit activity was extracellularly recorded in
      brain slices. The action of CART was studied in brains of 1. overweight adult
      rats previously subjected to early postnatal overfeeding in small litters (SL),
      compared to control litters, 2. normal rats that were deprived of food for 24 h,
      compared to fed rats. RESULTS: Hypothalamic dorsomedial neurons of controls, but
      not SL rats were significantly excited by CART, ventromedial neurons of SL rats
      were significantly inhibited. Also neurons of hungry rats were significantly
      inhibited. MAIN FINDINGS: Controls and overweight SL as well as fed and hungry
      rats differed significantly in the neuronal effects of CART. The predominant
      effect of the peptide did neither depend on weight nor on age of animals, but on
      neonatal development or nutritional state. CONCLUSION: The increase in inhibition
      by CART of ventromedial and dorsomedial neuronal activity could in vivo
      contribute to increased food intake and reduced energy expenditure of overweight
      SL as of hungry rats. Since leptin is able to change synaptic wiring and the
      expression of excitatory and inhibitory synapses already within short time, the
      increased expression of inhibitory responses to CART may reflect a general
      mechanism in adaptation of neuronal regulatory systems to the nutritional state,
      in fed, adult small-litter rats acquired during the postnatal critical
      differentiation period, thus leading to permanently altered function.

PMID- 15726017
TI  - Opioids are responsible for neurochemical feminization of the brain in prenatally
      stressed male rats.
AB  - OBJECTIVES: To study the role of opioids in early postnatal changes of the
      hypothalamic testosterone metabolism and catecholamine content underlying
      feminizing effect of prenatal stress on male sexual behavior in rats. MATERIAL
      AND METHODS: 10 day-old male and female offspring from mothers given naltrexone
      prior to daily 1-hour restraint during the last gestational week were used in the
      study. Aromatase and 5 alpha-reductase activities, noradrenaline and dopamine
      contents in the brain preoptic area and medial basal hypothalamus were studied by
      thin layer chromatography, radiometric and spectrofluorimetric techniques.
      RESULTS: Sexual dimorphism of testosterone metabolism enzymes activity and
      catecholamine content in discrete brain regions of 10 day-old rat pups was found.
      Prenatal stress attenuated these gender-related differences. Naltrexone pre
      treatment of stressed dams prevented modifying effect of prenatal stress on
      aromatase activity and noradrenaline content in the male preoptic area.
      CONCLUSIONS: The results of the study demonstrate preventive effect of naltrexone
      on stress-induced alterations of testosterone aromatization and noradrenaline
      concentration in the developing brain preoptic area associated with
      neuroendocrine control of the male sexual behavior in adult rats. These findings
      indicate that endogenic opioids mediate detrimental effect of prenatal stress on
      neurochemical determinants of the brain sexual differentiation that may underlie
      feminization of the male sexual behavior.

PMID- 15726018
TI  - The efficacy of human chorionic gonadotropin in retractile testis.
AB  - OBJECTIVES: To evaluate the efficacy of hCG therapy on retractile testis in
      various testicular locations and age groups. SETTING AND DESIGN: This study
      comprised 123 boys whose diagnosis were retractile testis with scrotal base, high
      scrotal and superficial inguinal localizations with an average age of 4,2 (1-8)
      years. METHODS: 123 boys with retractile testes were given a total dose of 9000
      hCG and its effect on scrotal base, high scrotal and superficial inguinal located
      testes were evaluated after 2 weeks and 6 months of completing hCG course. The
      patients were evaluated in four age groups such as less than 2 years of age,
      between 2-4, 4-6 years and more than 6 years of age and the response rates were
      also noted in these age groups. RESULTS: In unilateral cases, the response in
      base, high scrotal and superficial inguinal levels were found as 100%, 83,3%,
      72,7% respectively where as these rates were found as 100%, 92,6%, 76,3%
      respectively in bilateral cases after 2 weeks of hCG therapy. The response rates
      in less than 2 year old group, 2-4, 4-6 and more than 6 years group were found as
      0%, 80%, 78,7%, 100% respectively in unilateral cases and 33,3%, 90%, 86,9% and
      83,3% respectively in bilateral cases. After 6 months, reascend was observed in
      12,4% in unilateral group and 6,7% in bilateral group. MAIN FINDINGS: 72,7-100%
      of retractile testes respond to hCG administration with the highest response in
      the age of more than six year group. CONCLUSION: High response rates observed in
      retractile testes after hCG therapy in more than 2 years old age group indicate
      that hCG must be given as a primary treatment in retractile testes and orchiopexy
      for the failures. Also patients must be followed up closely for reascend cases.

PMID- 15726019
TI  - Norepinephrine attenuates hypoxia-inhibited thyrotropin-releasing hormone release
      in median eminence and paraventricular nucleus of rat hypothalamus.
AB  - OBJECTIVE: We have previously found that chronic hypoxia inhibited thyrotropin
      releasing hormone (TRH) mRNA expression in rat paraventricular nucleus (PVN).
      This study presented the effects of hypoxia on TRH secretion in rat hypothalamus,
      and the norepinephrine (NE) involvement in the modulation of TRH secretion during
      acute hypoxia exposure. SETTING AND DESIGN: Hypoxia was simulated at altitudes of
      5 km (10.8% O2) or 7 km (8.2% O2) in a ventilated hypobaric chamber, and control
      group was set at local altitude of 2.3 km (15.8% O2). The duration of hypoxia
      exposure was designed acutely and chronically for 0.5, 2, 24 h, 5, 10, and 30 d,
      respectively. TRH levels were measured by specific radioimmunoassay. RESULTS: The
      results showed that hypoxia of 5 km or 7 km significantly enhanced TRH levels of
      the ME and PVN, and reduced serum T3 levels in most hypoxia-exposed groups.
      Intraventricular injection (icv) of NE (4 nmol/L) induced a decrease in TRH
      levels in the median eminence (ME) and PVN, and an increased serum T3 levels
      following hypoxia of 7 km exposure for 2 h, compared with icv saline control,
      indicating TRH release increased. The stimulating effect of NE on the TRH
      secretion was abolished by icv antagonist of adrenergic alpha2-receptor,
      yohimbine (40 nmol/L). CONCLUSIONS: We conclude that acute and chronic hypoxia
      exposure produces an inhibition of hypothalamic TRH secretion from the ME and
      PVN. Central adrenergic system may play a stimulating role through alpha2
      receptor in the acute hypoxia-modulating TRH release from rat hypothalamus.

PMID- 15726020
TI  - Rosiglitazone, PPAR-gamma receptor ligand, decreases the viability of rat
      prolactin-secreting pituitary tumor cells in vitro.
AB  - OBJECTIVES: PPAR-gamma is a member of the nuclear receptor superfamily. PPAR
      gamma activation is associated with glucose metabolism regulation, adipocyte
      differentiation, inhibition of macrophage and monocyte activation and anti
      angiogenesis. PPAR-gamma ligands thiazolidinediones (TZDs) have been shown to
      inhibit the growth and secretory activity of several rat and murine pituitary
      tumors in vivo as well as in vitro (ACTH-secreting AtT20, PRL- and GH-secreting
      GH3, LH-secreting LbetaT2 and alpha-T3 cells). TZDs have been demonstrated to
      induce G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph,
      murine corticotroph and gonadotroph pituitary tumor cells. In the present study
      we have investigated for the first time the effects of PPAR-gamma receptor ligand
      rosiglitazone on the rat estrogens-induced, PRL-secreting pituitary tumor cells
      in vitro. MATERIAL AND METHODS: Four weeks old male Fischer 344 rats were used in
      the experiment. Pituitary tumors were induced by subcutaneous implantation of
      capsules containing diethylstilboestrol (DES). Eight weeks after the implantation
      of capsules the rats were sacrificed and pituitary tumors were collected.
      Tumorous cells were isolated and exposed in the primary culture to rosiglitazone
      at the concentrations 10(-10) - 10(-4)M for 24 hours. The cell growth was
      estimated by the measurement of the cells metabolic activity using the EZ4U
      system. RESULTS: We have demonstrated that rosiglitazone at the concentrations
      10(-10) - 10(-4)M significantly decreases the number of viable rat PRL-secreting
      pituitary tumor cells in vitro. CONCLUSION: These results suggest that PPAR-gamma
      receptor agonists thiazolidinediones may be useful in the medical treatment of
      pituitary tumors.

PMID- 15726022
TI  - A novel observation: melatonin's interaction with malondiadehyde.
AB  - OBJECTIVES: A purpose of this study is to determine whether melatonin, a novel
      antioxidant, can interact with malondialdehyde in an in vitro condition. METHODS:
      The reaction kinetics and thermodynamics of this reaction have been performed and
      a new product has been identified using liquid chromatography onlining with mass
      spectrometry. RESULTS: A new product generated with an interaction of melatonin
      and malondialdehyde has been identified to be a three-ring structure with a
      molecular weight 286, which has the specific wavelength absorption with the
      maximum at 345 nm. The reaction was completed within a few minutes and the
      product was proportional to the concentrations of the reactants. Based on its
      molecular weight and the deduced structure of the new product, we speculate that
      this reaction occurs between one melatonin molecule and one malondialdehyde and
      to form a 3 ring conjugated adduct. CONCLUSION: This is the first report to show
      that melatonin directly interacts with malondialdehyde to form a new product. The
      findings suggest that melatonin may detoxify unsaturated carbonyls and protect
      against cellular damage induced by oxidative stress.

PMID- 15726021
TI  - Season- and gender-dependent changes in the immune function of Siberian hamsters
      (Phodopus sungorus).
AB  - OBJECTIVES: Siberian hamsters are photoperiodic animals exhibiting seasonality of
      reproduction and other physiological functions. Thus, the influence of
      photoperiod on the in vitro activity of selected immune cells from male and
      female hamsters challenged with peritoneal inflammation was examined. METHODS:
      Animals were housed for 8-10 weeks in LD (L:D=18:6) or SD (L:D=6:18). Peritoneal
      leukocytes (PTLs) and splenocytes were isolated form male and female and
      testicular macrophages (TMs) from male hamsters, intact or challenged with
      zymosan-induced peritonitis. PTL and TM activity was assessed by the level of
      reactive oxygen species (ROS) measured with the use of flow cytometry and
      splenocyte activity -- by the spontaneous and mitogen-stimulated proliferation
      measured with the use of 3H-tymidine incorporation test. RESULTS: Results
      obtained indicate that the immune system of Siberian hamsters is highly sexually
      dimorphic. Experimentally evoked peritonitis developed differently in males and
      females: only in LD male hamsters an increase in PTL activity was observed after
      zymosan treatment. Also, in LD males, PTL activity was higher in LD than in SD.
      Developing peritonitis exerted in these animals a stimulatory effect on
      splenocyte proliferation but had no influence on cells residing in the immune
      privileged testes. Splenocyte proliferation, both spontaneous and PHA-stimulated,
      depended on the photoperiod studied: in LD it was significantly higher than in SD
      in animals of both sexes. CONCLUSIONS: Innate immunity of Siberian hamsters
      studied on the peritoneal inflammation model, seems to be gender- and photoperiod
      dependent. Moreover, local inflammation may affect other lymphoid organs but does
      not influence immune-privileged sites.

PMID- 15726023
TI  - Riedel's thyroiditis in a patient with multiple sclerosis.
AB  - Our patient developed Riedel's thyroiditis soon after having an exacerbation of
      multiple sclerosis (MS). MS has been associated with other autoimmune diseases,
      including thyroiditis, and both Hashimoto's thyroiditis and subacute thyroiditis
      have been described in connection with MS. Yet, we are not aware of any other
      patient reported to have concomitant MS and Riedel's thyroiditis. The association
      between MS and Riedel's thyroiditis remains obscure but may reflect an autoimmune
      disorder common to both diseases.

PMID- 15726024
TI  - Ziprasidone-induced galactorrhea: a case report.
AB  - OBJECTIVES: Second-generation antipsychotics presumably lack the typical side
      effects of conventional antipsychotics. METHODOLOGY: A 34 year old Caucasian
      woman with ICD-10 diagnosis of Recurrent depressive disorder with current
      moderate symptoms, and with a history of repeated self-injury was treated with
      lithium, clonazepam and ziprasidone. RESULTS: On the ninth day of ziprasidone
      administration, galactorrhea appeared. After 36 days of ziprasidone therapy,
      galactorrhea persisted. The prolactin plasma level was 28 ng/ml. Thyroid tests
      (TSH,T3,T4) and the lithium plasma level were within the normal range during
      ziprasidone treatment. Two weeks after the ziprasidone withdrawal, galactorrhea
      disappeared and the prolactin level decreased down to 18 ng/ml. CONCLUSION:
      Psychiatrists should be aware that even second-generation antipsychotics,
      including ziprasidone, have a propensity to cause side-effects associated with
      the dopamine D2 receptor blockade, such as galactorrhea.

PMID- 15726025
TI  - Concomitancy of mutation in FRDA gene and FMR1 premutation in 58 year-old woman.
AB  - DNA testing broadens diagnostic tools available for hereditary ataxias. However,
      together with current knowledge of genes and their mutations crop up new
      phenotype figures of diseases already well known. Diagnostic problems in practice
      can consist in part due to the very similar symptoms of hereditary ataxias and
      acquaintance in or availability of new techniques such as DNA testing and result
      in misdiagnosis. We present a case study of a 57 year-old woman with both
      expansion of the triplet repetitive sequence of FRDA gene and a premutation in
      FMR1 gene. At present we diagnose her with Very Late Onset Friedreich s ataxia,
      but we advise of possible combinations or aggravations of her symptoms due to
      manifestation of Fragile X premutation tremor/ataxia syndrome. In nontypical
      phenotypes of DNA verifying hereditary ataxias we recommend searching of
      comorbidity, specifically from a range of hereditary ataxias with very similar
      spectra of symptoms.

PMID- 15726026
TI  - Relief of internal snapping hip syndrome in a marathon runner after chiropractic
      treatment.
AB  - OBJECTIVE: To discuss the assessment, diagnosis and chiropractic management of a
      patient with sacroiliac joint dysfunction (SIJ) complicated by psoas major
      snapping hip syndrome (coxa saltans interna). CLINICAL FEATURES: A 32-year-old
      male marathon runner experienced low-back and left hip pain without radiation
      accompanied by a "popping" in the anterior hip. He ran approximately 100 to 150
      km/wk for the prior 3 years. He had stopped running for the previous 3 weeks
      because of worsening and consistent pain. INTERVENTION AND OUTCOME: Treatment
      consisted of side posture SIJ "diversified" manipulation and myofascial release
      to the psoas muscle twice weekly for 2 weeks. The patient was also taught
      proprioceptive neuromuscular facilitation exercises of the psoas and iliotibial
      band muscles. He was instructed to substitute swimming instead of running on a
      daily basis. Reassessment at 3 weeks found the patient without pain in his hip or
      back and no clicking or popping in his left hip. CONCLUSION: Clinicians should
      consider that runners who present with coexisting SIJ dysfunction and internal
      snapping hip syndrome may benefit from the combined management of both
      conditions.

PMID- 15726029
TI  - Long-term follow-up of a randomized clinical trial assessing the efficacy of
      medication, acupuncture, and spinal manipulation for chronic mechanical spinal
      pain syndromes.
AB  - OBJECTIVE: To assess the long-term benefits of medication, needle acupuncture,
      and spinal manipulation as exclusive and standardized treatment regimens in
      patients with chronic (>13 weeks) spinal pain syndromes. STUDY DESIGN: Extended
      follow-up (>1 year) of a randomized clinical trial was conducted at the
      multidisciplinary spinal pain unit of Townsville's General Hospital between
      February 1999 and October 2001. PATIENTS AND METHODS: Of the 115 patients
      originally randomized, 69 had exclusively been treated with the randomly
      allocated treatment during the 9-week treatment period (results at 9 weeks were
      reported earlier). These patients were followed up and assessed again 1 year
      after inception into the study reapplying the same instruments (ie, Oswestry Back
      Pain Index, Neck Disability Index, Short-Form-36, and Visual Analogue Scales).
      Questionnaires were obtained from 62 patients reflecting a retention proportion
      of 90%. The main analysis was restricted to 40 patients who had received
      exclusively the randomly allocated treatment for the whole observation period
      since randomization. RESULTS: Comparisons of initial and extended follow-up
      questionnaires to assess absolute efficacy showed that only the application of
      spinal manipulation revealed broad-based long-term benefit: 5 of the 7 main
      outcome measures showed significant improvements compared with only 1 item in
      each of the acupuncture and the medication groups. CONCLUSIONS: In patients with
      chronic spinal pain syndromes, spinal manipulation, if not contraindicated, may
      be the only treatment modality of the assessed regimens that provides broad and
      significant long-term benefit.

PMID- 15726030
TI  - Subjective nature of lower limb radicular pain.
AB  - BACKGROUND: Lumbar pathologies may cause the perception of leg pain, but the
      character of this pain has not been described. Diagnosis is often based on
      dermatomal charts, but observations reveal that the pain is not typically
      perceived on the skin. OBJECTIVE: To document the incidence of superficial versus
      deep pain localization among patients with lumbar radicular pain. METHODS: Twenty
      five patients with lower limb radicular pain were questioned to determine the
      specific localization of their pain. The investigator categorized the pain
      location into general areas (eg, posterior thigh or anterior leg). Patients were
      asked if their pain was perceived as being on the skin or deep, as a forced
      choice question. These data were gathered in 2 conditions: at rest (spontaneous
      pain) and during a straight leg raise test (mechanically evoked pain). Data were
      recorded using a standardized form for later analysis. RESULTS: In all cases,
      symptoms were reported to be in deep structures. Pain was typically reported at
      sites correlated with multiple spinal levels. CONCLUSION: Because radicular pain
      symptoms are perceived in deep structures rather than on the skin, the diagnostic
      value of dermatomal charts is questioned. Clinicians are advised to be specific
      when questioning patients with radicular pain symptoms and to refer to myotomal
      and sclerotomal charts when making diagnoses.

PMID- 15726031
TI  - Consent or submission? The practice of consent within UK chiropractic.
AB  - BACKGROUND: A patient's right to accept or reject proposed treatment is both an
      ethical and legal tenet. Valid consent is a multifaceted, controversial and often
      complicated process, yet practitioners are obligated to try to obtain consent
      from their patients. Its omission is a common basis for malpractice suits and
      increasing utilization of complementary and alternative services in conventional
      medical settings is intensifying the focus on medical liability issues. This has
      important implications for individual professions and their members. OBJECTIVE:
      To investigate approaches to consent among a small (n = 150) sample of practicing
      UK chiropractors. RESULTS: Of 150 randomly selected chiropractic practitioners in
      the United Kingdom, 55% responded. Of these, 25% report not informing patients of
      physical examination procedures prior to commencement. By contrast, only 6% do
      not fully explain proposed treatment, although over one-third do not advise
      patients of alternative available treatments. Nearly two-thirds of the
      practitioners report that there are no specific procedures for which they always
      obtain written consent and 18% that there are no instances in which they document
      when verbal consent has been obtained. Ninety-three percent said they always
      discuss minor risk with their patients but only 23% report always discussing
      serious risk. When treatment carries a possible risk of a major side-effect only
      14% of the sample obtain formal written consent. Documentation of patient
      understanding is omitted by 75% of practitioners in this sample. CONCLUSION:
      Results suggest that valid consent procedures are either poorly understood or
      selectively implemented by UK chiropractors.

PMID- 15726032
TI  - Neck muscle endurance, self-report, and range of motion data from subjects with
      treated and untreated neck pain.
AB  - BACKGROUND: Despite the high prevalence and cost of neck-pain problems, there is
      currently little data available on the physical characteristics associated with
      different levels of neck pain. OBJECTIVE: To investigate associations between
      categories of response to neck pain/discomfort and (1) the endurance time of neck
      muscles, neck range of motion (ROM), and neck and head morphology, (2)
      sensitization or stretch effects arising from repeating end-of-range
      measurements, and (3) self-report data from neck pain and disability
      questionnaires. DESIGN: A cross-sectional study design. METHODS: Fifty-five
      Australian volunteers with and without neck pain, who were not taking time off
      work, were measured for neck muscle endurance, active neck ROM, craniocervical
      and thoracic posture, neck length, and head circumference and completed
      questionnaires about any neck pain/discomfort and disability. RESULTS: Twenty-two
      subjects reported a level of neck pain/discomfort that had required treatment
      (treated neck pain), a group of 17 subjects reported experiencing low-level neck
      pain/discomfort on a recurrent basis for which they had not sought treatment
      (untreated neck pain), whereas 16 subjects had no experience of neck pain or
      discomfort (no pain). Neck muscle endurance time was significantly lower for both
      pain groups. The affective dimension of the Short-Form McGill Pain Questionnaire
      and neck disability questionnaires were scored significantly higher by subjects
      who had sought treatment than by those in either of the untreated groups. Both
      pain groups showed a range decrease for most directions of neck motion at second
      measurement. CONCLUSIONS: Neck muscle endurance times, repeated end-ROM testing,
      the Short-Form McGill Pain Questionnaire, and disability questionnaires may
      distinguish between groups with untreated, treated, and no neck pain.

PMID- 15726033
TI  - Experience and practice organization in learning a simulated high-velocity low
      amplitude task.
AB  - OBJECTIVE: To evaluate the effect of practice schedule, type of feedback, and
      experience level on simulated force production accuracy in chiropractic students.
      METHODS: Thirty-three chiropractic students simulated a high-velocity low
      amplitude prone thoracic spine manipulation. Three force goals based on percent
      of maximum thrusting ability were used in blocked and random variable practice.
      Participants received either visual feedback or knowledge of performance feedback
      regarding their force-time history. Serial retention tests without feedback
      followed blocked and random variable practice. Peak and average rates of thrust
      development, as well as the constant error, absolute constant error, and variable
      error of peak force production, were calculated. CONCLUSION: Familiarity and
      practice of high-velocity low-amplitude spinal manipulation resulted in greater
      accuracy of peak force production. Lower error scores were observed in
      acquisition with blocked variable practice. However, short-term accuracy was
      enhanced in retention when participants had used random variable practice. Random
      variable practice combined with visual feedback improved force production
      accuracy in retention. The variability of peak force production increased to 61%
      of maximum thrusting ability and then decreased. The greatest accuracy with least
      variability of peak force production was seen near 75% of maximum thrusting
      ability.

PMID- 15726034
TI  - Autonomic nervous system function among individuals with acute musculoskeletal
      injury.
AB  - OBJECTIVE: To determine differences in peripheral and cardiovascular autonomic
      function between individuals with acute musculoskeletal injury (<1 week) and
      healthy controls. METHODS: Autonomic cardiovascular modulation, baroreceptor
      sensitivity, skin conductance, and peripheral skin temperature were obtained in 6
      subjects with acute musculoskeletal injury and 6 age- and sex-matched controls.
      Power spectral analysis was performed on both beat-to-beat R-R intervals and
      continuous systolic blood pressure (SBP) peaks. Baroreceptor sensitivity was
      derived using both heart rate and blood pressure spectral analysis components.
      RESULTS: The SD of R-R intervals was significantly different for the acute injury
      group relative to controls (49.8 +/- 10.5 vs 76.8 +/- 12.7 ms; P < .01).
      Continuous SBP peaks and skin conductance (sympathetic vasomotor and sudomotor
      indices, respectively) were significantly higher (59.6 +/- 6.7 vs 23.8 +/- 6.4 mm
      Hg2 /Hz, and 3.87 +/- 1.04 vs 2.19 +/- 0.3 mhos; P < .01, respectively) and
      baroreceptor sensitivity lower (0.97 +/- 0.07 vs 1.10 +/- 0.08 mm Hg; P < .02) in
      the acute injury group compared with controls. Regression analysis revealed a
      significant relationship between skin conductance and continuous SBP peaks (r =
      0.75; P < .01). CONCLUSIONS: These findings suggest that interaction between
      cutaneous and vasomotor sympathetic neurons in response to acute musculoskeletal
      injury, reflected as increased afferent input from sensitized nociceptors and
      other sensory neurons, results in alterations in autonomic function.

PMID- 15726035
TI  - Interexaminer reliability of the deltoid and psoas muscle test.
AB  - OBJECTIVE: To determine if 2 practitioners of differing skill levels could
      reliably agree on the presence of a weak or strong deltoid or psoas muscle. STUDY
      DESIGN: Interexaminer reliability study of 2 common muscle tests. MAIN OUTCOME
      MEASURES: Cohen kappa (unweighted) scores, observer agreement, and 95% confidence
      intervals (CIs). RESULTS: The results showed that an experienced and a novice
      practitioner have good agreement when using repeated muscle test procedures on
      the deltoid ( kappa 0.62) and the psoas ( kappa 0.67). CONCLUSIONS: The manual
      muscle test procedures using the anterior deltoid or psoas showed good
      interexaminer reliability when used by an experienced and a novice user. These
      techniques may be used between practitioners in multidoctor assessment/management
      programs.

PMID- 15726036
TI  - Cervical artery dissection. A comparison of highly dynamic mechanisms:
      manipulation versus motor vehicle collision.
AB  - OBJECTIVE: To examine the similarities and dissimilarities between cervical
      chiropractic manipulative therapy and whiplash, and their respective relation to
      cervical artery dissection. DATA SOURCES: A literature synthesis used MEDLINE
      PubMed and MANTIS literature searches. A total list of 99 relevant articles was
      generated. Additional references were collected from citations incorporated
      within the included articles. RESULTS: Both neck manipulation and motor vehicle
      collision events apply loads to the spinal column rapidly. While neck
      manipulation loads are slower to develop and displacements smaller, they may
      reach peak amplitudes on maximum effort comparable to those seen in low-velocity
      collision experiments. In contrast to reports that the vertebral artery
      experiences elongations exceeding its physiological range by up to 9.0 mm during
      simulated whiplash, strains incurred during cervical manipulative therapy have
      been reported to be approximately one ninth of those required for mechanical
      failure, comparable to forces encountered in the course of diagnostic range of
      motion examination. Additionally, long-lasting abnormalities of blood flow
      velocity within the vertebral artery have been reported in patients following
      common whiplash injuries, whereas no significant changes in vertebral artery peak
      flow velocity were observed following cervical chiropractic manipulative therapy.
      CONCLUSIONS: Perceived causation of reported cases of cervical artery dissection
      is more frequently attributed to chiropractic manipulative therapy procedures
      than to motor vehicle collision related injuries, even though the comparative
      biomechanical evidence makes such causation unlikely. The direct evidence
      suggests that the healthy vertebral artery is not at risk from properly performed
      chiropractic manipulative procedures.

PMID- 15726038
TI  - A revised definition of manipulation.

PMID- 15726037
TI  - Postlymphoproliferative disorder affecting bone after a renal transplantation.
AB  - OBJECTIVE: To illustrate a posttransplant lymphoproliferative lymphoma presenting
      as a solitary osseous lesion situated in the rib. CLINICAL FEATURES: A 53-year
      old man was referred to a surgical department because of persistent local pain
      over the lower part of his left posterior hemithorax. Due to a previous history
      of chronic glomerulonephritis, a renal transplant was performed 7 years
      previously, followed by immunosuppressive therapy with azathioprine
      cyclophosphamide. INTERVENTION AND OUTCOME: Surgical removal of the rib lesion
      was performed because of the patient's history of the organ transplant. The
      histological study of the surgically removed tissue revealed diffuse infiltration
      of the marrow by lymphoid-like cells. There was evidence of interstitial
      fibrosis, and further immunohistochemical examination showed the presence of B
      cells in the specimen confirming the diagnosis of B-cell lymphoma. CONCLUSION:
      This case report discusses an unusual presentation of a lymphoma induced by
      immunosuppressive therapy in a patient who had received an organ transplant. Such
      lesions may appear in any organ or system, although this is distinctively unusual
      to involve the skeletal system.

PMID- 15726039
TI  - The role of the institution in developing the next-generation chiropractor:
      clinician and researcher.

PMID- 15726040
TI  - Influence of active release technique on quadriceps inhibition and strength: a
      pilot study.

PMID- 15726041
TI  - Informed consent: a potential dilemma for complementary medicine.

PMID- 15726042
TI  - Informed consent: a potential dilemma for complementary medicine.

PMID- 15726043
TI  - Creator and keeper of the flame of emergency medicine: John G. Wiegenstein, MD,
      1930-2004.

PMID- 15726044
TI  - Images in emergency medicine. Forearm furuncle resulting from community
      associated methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 15726045
TI  - Evaluation of an emergency department-based enrollment program for uninsured
      children.
AB  - STUDY OBJECTIVE: We evaluate the effectiveness of an emergency department (ED)
      based outreach program in increasing the enrollment of uninsured children.
      METHODS: The study involved placing a full-time worker trained to enroll
      uninsured children into Medicaid or the State Children's Health Insurance Program
      in an inner-city academic children's hospital ED. Analysis was carried out for
      outpatient ED visits by insurance status, average revenue per patient from
      uninsured and insured children, proportion of patients enrolled in Medicaid and
      State Children's Health Insurance Program through this program, estimated
      incremental revenue from new enrollees, and program-specific incremental costs. A
      cost-benefit analysis and breakeven analysis was conducted to determine the
      impact of this intervention on ED revenues. RESULTS: Five thousand ninety-four
      uninsured children were treated during the 10 consecutive months assessed, and
      4,667 were treated during program hours. One thousand eight hundred and three
      applications were filed, giving a program penetration rate of 39%. Eighty-four
      percent of applications filed were resolved (67% of these were Medicaid). Average
      revenue from each outpatient ED visit for Medicaid was US135.68 dollars, other
      insurance was US210.43 dollars, and uninsured was US15.03 dollars. Estimated
      incremental revenue for each uninsured patient converted to Medicaid was US120.65
      dollars. Total annualized incremental revenue was US224,474 dollars, and the net
      incremental revenue, after accounting for program costs, was US157,414 dollars
      per year. CONCLUSION: A program enrolling uninsured children at an inner-city
      pediatric ED into government insurance was effective and generated revenue that
      paid for program costs.

PMID- 15726046
TI  - The science of common sense: integrating health and human services in the
      hospital emergency department.

PMID- 15726047
TI  - Creating effective learning in today's emergency departments: how accomplished
      teachers get it done.
AB  - STUDY OBJECTIVES: Significant impediments to effective emergency department (ED)
      teaching compromise what could otherwise be an excellent learning milieu. There
      is little literature to guide faculty development around specific emergency
      medicine teaching techniques. We determine what recognized experts in emergency
      medicine teaching consider to be the important clinical teaching behaviors that
      make them good teachers, the main impediments to good teaching in EDs, and
      important prerequisites for a good ED teacher. METHODS: This was a structured
      telephone survey with qualitative grounded-theory analysis. Participants were
      current Canadian emergency medicine teaching faculty who have won awards, been
      promoted, or received persistent excellent evaluations according to their ED
      teaching. Participants underwent a 45- to 60-minute standardized structured
      telephone interview. Interviews were transcribed and independently coded by 2
      investigators using a grounded-theory approach. The codes were merged by
      consensus, and the data were recoded. Twenty percent of data were then coded by
      both investigators to estimate interrater reliability of final coding.
      Discrepancies were resolved by agreement. RESULTS: Of 43 potential participants,
      33 were still in practice, available, and willing to participate. Twelve ED
      specific, practical, implementable strategies representing the general themes of
      learner-centeredness, active learning, individual relevance, and efficiency
      emerged. Participants collectively identified 6 significant impediments to
      teaching and 9 prerequisites to being an effective ED teacher. CONCLUSION:
      Accomplished emergency medicine teaching faculty identify with common impediments
      to ED teaching yet are able to describe practical, easily implemented strategies
      that they believe make them good teachers. They also take advantage of basic
      prerequisites for good teaching.

PMID- 15726048
TI  - Emergency medicine clerkship directors: defining the characteristics of the
      workforce.
AB  - STUDY OBJECTIVE: Clerkship directors design and implement educational programs
      for students. Scholarly productivity is necessary for academic advancement. We
      define characteristics of emergency medicine clerkship directors and evaluate
      determinants of scholarly productivity and job satisfaction. METHODS: This is a
      cross-sectional survey. Clerkship directors for emergency medicine senior
      rotations completed a confidential online questionnaire. Demographic data were
      analyzed with descriptive statistics. Scholarly productivity and job satisfaction
      indices were created for multivariate analysis. RESULTS: One hundred eleven (82%)
      of 136 directors responded (age 38.9+/-7.0 years; men 72.1%; junior academic rank
      72.1%; served as clerkship directors for < or =5 years 77.4%; formal training in
      education: medical education fellowship 36%, teaching credential 12.7%, emergency
      medicine subspecialty fellowship 6.3%; support for clerkship director's
      activities: clinical hours reduction 2.7+/-2.3 weekly; minimal training for
      clerkship director's role 85.6%; ongoing professional development 40.5%;
      scholarly productivity: < or =5 peer-reviewed publications 78.4%, grant 28%,
      textbook chapter 65%; plan to be clerkship director in 5 years 63%; perceived
      support from supervisor 88%; perceived value from colleagues 81%; perception that
      clerkship directors is as important as residency director 47.8%). Multivariate
      regression shows a significant effect of medical education fellowship (P =.013)
      and subspecialty training (P =.044). Departmental support enhances the effect of
      medical education (P =.008) or subspecialty (P =.026) fellowships and improves
      productivity for senior faculty (P =.047). Multivariate regression explaining job
      satisfaction shows a positive effect of reduced clinical hours (P =.038) and
      increased faculty development (P =.033). CONCLUSION: Most emergency medicine
      clerkship directors are junior faculty with minimal release time or training for
      their positions.

PMID- 15726049
TI  - Advanced training in pediatric emergency medicine in the United States, Canada,
      United Kingdom, and Australia: an international comparison and resources guide.
AB  - Pediatric emergency medicine is an important subspecialty of pediatrics and
      emergency medicine. It is a well-established subspecialty in some countries and
      less well developed or evolving in others. We set out to develop a resource guide
      and document the current status of pediatric emergency medicine training across 4
      countries (United States, Canada, United Kingdom, and Australia). This article
      also aims to provide a starting point for pediatric or emergency physicians
      charged with the development of pediatric emergency medicine training programs in
      countries without such programs.

PMID- 15726050
TI  - Emergency department crowding: the effect on resident education.

PMID- 15726051
TI  - Derivation and validation of a Bayesian network to predict pretest probability of
      venous thromboembolism.
AB  - STUDY OBJECTIVE: A Bayesian network can estimate a numeric pretest probability of
      venous thromboembolism on the basis of values of clinical variables. We determine
      the accuracy with which a Bayesian network can identify patients with a low
      pretest probability of venous thromboembolism, defined as less than or equal to
      2%. METHODS: Using commercial software, we derived a population of Bayesian
      networks from 25 input variables collected on 3,145 emergency department (ED)
      patients with suspected venous thromboembolism who underwent standardized
      testing, including pulmonary vascular imaging, and 90-day follow-up (11.0% of
      patients were venous thromboembolism positive). The best-fit Bayesian network was
      selected using a genetic algorithm. The selected Bayesian network was tested in a
      validation population of 1,423 ED patients prospectively evaluated for venous
      thromboembolism, including 90-day follow-up (8.0% were venous thromboembolism
      positive). The Bayesian network probability estimate was normalized to a score of
      0% to 100%. RESULTS: Of 1,423 patients in the validation cohort, 711 (50%; 95%
      confidence interval [CI] 47% to 52%) had a score less than or equal to 2% that
      predicted a low pretest probability. Of these 711 patients, 700 (98.5%; 95% CI
      97.2% to 99.2%) had no venous thromboembolism at follow-up. CONCLUSION: A
      Bayesian network, derived and independently validated in ED populations,
      identified half of the validation cohort as having a low pretest probability (<
      or =2%); 98.5% of these patients were correctly classified by the network.

PMID- 15726052
TI  - Placing the Bayesian network approach to patient diagnosis in perspective.

PMID- 15726053
TI  - A call for expanding the role of the emergency physician in the care of patients
      with asthma.

PMID- 15726054
TI  - Improving quality of asthma care after emergency department discharge: evidence
      before action.

PMID- 15726055
TI  - The mortality of untreated pulmonary embolism in emergency department patients.
AB  - Much of the literature on pulmonary embolism that is commonly referenced by
      emergency physicians begins with statistics concerning how often the diagnosis is
      missed and the lethality of pulmonary embolism if undiagnosed and untreated. It
      is likely that many emergency physicians continue to pursue an aggressive
      diagnostic strategy even in low-risk patients because of concerns about the
      potential for poor patient outcome and the medicolegal consequences of a missed
      diagnosis. The believed and often-quoted mortality and recurrence rates for
      untreated or missed pulmonary embolism are 26% to 30%. However, these figures
      originate from investigations that have little relevance to modern emergency
      medicine, which include studies dating to the 1940s, many of which have
      significant methodologic pitfalls. These data are also based primarily on either
      inpatient or autopsy populations, neither of which is representative of patients
      treated in the emergency department (ED). Analysis of untreated or missed
      pulmonary embolism in ambulatory patients reveals mortality and recurrence rates
      of less than 5%. This article discusses the background of commonly quoted
      pulmonary embolism statistics and highlights the need for future investigations
      enrolling ED patients that focus on disease outcome in this population.

PMID- 15726057
TI  - Community-associated methicillin-resistant Staphylococcus aureus: is it in your
      community and should it change practice?

PMID- 15726056
TI  - High prevalence of methicillin-resistant Staphylococcus aureus in emergency
      department skin and soft tissue infections.
AB  - STUDY OBJECTIVE: We sought to determine the prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) among emergency department (ED) patients with skin
      and soft tissue infections, identify demographic and clinical variables
      associated with MRSA, and characterize MRSA by antimicrobial susceptibility and
      genotype. METHODS: This was a prospective observational study involving a
      convenience sample of patients who presented with skin and soft tissue infections
      to a single urban public hospital ED in California. Nares and infection site
      cultures were obtained. A health and lifestyle questionnaire was administered,
      and predictor variables independently associated with MRSA were determined by
      multivariate logistic regression. All S aureus isolates underwent antibiotic
      susceptibility testing. Eighty-five MRSA isolates underwent genotyping by pulsed
      field gel electrophoresis, staphylococcal chromosomal cassette mec (SCC mec )
      typing, and testing for Panton-Valentine leukocidin genes. RESULTS: Of 137
      subjects, 18% were homeless, 28% injected illicit drugs, 63% presented with a
      deep or superficial abscess, and 26% required admission for the infection. MRSA
      was present in 51% of infection site cultures. Of 119 S aureus isolates (from
      infection site and nares), 89 (75%) were MRSA. Antimicrobial susceptibility among
      MRSA isolates was trimethoprim/sulfamethoxazole 100%, clindamycin 94%,
      tetracycline 86%, and levofloxacin 57%. Among predictor variables independently
      associated with MRSA infection, the strongest was infection type being furuncle
      (odds ratio 28.6). Seventy-six percent of MRSA cases fit the clinical definition
      of community associated. Ninety-nine percent of MRSA isolates possessed the SCC
      mec IV allele (typical of community-associated MRSA), 94.1% possessed Panton
      Valentine leukocidin genes, and 87.1% belonged to a single clonal group (ST8:S).
      CONCLUSION: In this urban ED population, MRSA is a major pathogen in skin and
      soft tissue infections. Although studies from other practice settings are needed,
      MRSA should be considered when empiric antibiotic therapy is selected for such
      infections.

PMID- 15726058
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Imported Lassa fever--New Jersey, 2004.

PMID- 15726060
TI  - Evidence-based emergency medicine/rational clinical examination abstract.
      Clinical assessment of hypovolemia.

PMID- 15726061
TI  - Evidence-based emergency medicine/systematic review abstract. Do corticosteroids
      decrease mortality in sepsis?

PMID- 15726062
TI  - Thanksgiving in blue and pink.

PMID- 15726063
TI  - Images in emergency medicine. Air emboli.

PMID- 15726064
TI  - The use of serial ocular ultrasonography in the care of patients with head
      injury.

PMID- 15726065
TI  - Fatal cerebral edema after moderate valproic acid overdose.

PMID- 15726066
TI  - Fasciotomy after envenomation: measure twice and cut once.

PMID- 15726069
TI  - Positional-dependent changes in glenohumeral joint contact pressure and force:
      possible biomechanical etiology of posterior glenoid wear.
AB  - The purpose of this study was to simulate the forces in the individual
      periscapular muscles and investigate the possible biomechanical etiology of
      posterior erosion of the glenoid. Twelve fresh-frozen human cadaveric shoulders
      were used with a custom shoulder jig that uses independently controlled pneumatic
      cylinders to apply forces across the tendon of each muscle. The simulated muscle
      forces included the rotator cuff, the deltoid, the latissimus dorsi, and the
      pectoralis major. The shoulders were tested in 12 overhead activity positions. A
      6-degree-of-freedom load cell was used to measure the glenohumeral joint forces,
      and the glenohumeral contact pressures and areas were measured by use of Fuji
      pressure-sensitive film. There were no significant differences in glenohumeral
      joint forces between 60 degrees and 90 degrees of vertical abduction or between
      60 degrees and 90 degrees of external rotation. At 70 degrees of horizontal
      adduction from the scapular plane, there was a significant decrease in superior
      force, a significant increase in posteriorly directed force, and a significant
      decrease in compression when compared with 30 degrees and 50 degrees of
      horizontal adduction ( P < .05). Similar statistical trends were seen for 60
      degrees of vertical adduction. For the glenohumeral contact area and pressure, a
      significant decrease in contact area was seen between 30 degrees of horizontal
      adduction and 70 degrees of horizontal adduction for both 60 degrees and 90
      degrees of vertical adduction ( P < .05). A significant increase in contact
      pressure was seen at 70 degrees of horizontal adduction compared with 50 degrees
      and 30 degrees ( P < .05). The contribution of the humerothoracic muscles is
      significant and should be considered for proper restoration of glenohumeral joint
      biomechanics. Furthermore, asymmetric loading with excessive or repetitive
      overhead activities may eventually lead to posterior glenoid erosion.

PMID- 15726070
TI  - Prosthetic positioning in total shoulder arthroplasty.
AB  - Accurate positioning of the prosthetic humeral head is necessary to reproduce
      normal glenohumeral kinematics and to avoid damage to the rotator cuff and
      impingement on the glenoid component or coracoacromial arch. Proper positioning
      of the head requires accurate placement of the stem and prosthetic designs that
      allow the head position to adapt to the variations in both normal and pathologic
      humeral anatomy. Glenoid malpositioning can lead to both humeral instability and
      increased stress of the glenoid component that may lead to premature glenoid
      loosening. This review summarizes the cadaveric and finite-element model that
      defines the abnormalities associated with humeral and glenoid component
      malpositioning.

PMID- 15726071
TI  - Biomechanics of shoulder capsulorrhaphy procedures.
AB  - Nonanatomic capsulorrhaphy procedures and reconstructions used to treat shoulder
      instability create mechanical alterations to the glenohumeral joint that lead to
      eventual arthrosis. Current capsulorrhaphy procedures have evolved toward
      restoring normal anatomy and have stimulated relevant anatomic research. Analysis
      of the subscapularis insertion has demonstrated a superior tendinous insertion
      and an inferior muscular insertion with the inferior glenohumeral capsule
      consistently located beneath the muscular insertion of the subscapularis. In
      addition, 2 types of inferior humeral capsular attachments have been identified.
      The anterior capsular insertion may bifurcate into a superior internal fold
      adjacent to the articular cartilage and an inferior external fold on the humeral
      surgical neck. Alternatively, the capsule may insert over a broad area on the
      surgical neck. Therefore, releasing the muscular portion of the subscapularis and
      both capsular folds or the entire broad capsular insertion enhances proper
      shifting of the capsule during laterally based capsulorrhaphy procedures.
      Biomechanical studies allow direct study of the different parameters involved in
      capsulorrhaphy procedures, and several recent studies have improved our
      understanding. Anterior tightening procedures such as the Putti-Platt or Magnuson
      Stack procedure, as well as a tight Bankart repair, result in a loss of external
      rotation and maximum elevation. Furthermore, this type of operative intervention
      creates greater posterior joint loads and abnormal posteroinferior humeral head
      subluxation, leading to pain and arthrosis. Anatomic capsulorrhaphy procedures
      produce more normal joint mechanics. Current and future studies will evaluate new
      arthroscopic capsulorrhaphy techniques.

PMID- 15726072
TI  - Total shoulder arthroplasty: glenoid component design.
AB  - Although Charles Neer's original glenoid component underwent several
      modifications, the all-polyethylene, keeled component with a radius of curvature
      that conformed to the humeral radius of curvature and that was implanted with
      cement became the glenoid implant of choice. Neer reported approximately a 30%
      incidence of radiolucent lines; however, only 2 of 615 glenoids were revised for
      loosening. Other surgeons have reported radiolucent lines in up to 90% of glenoid
      components and have correlated symptoms with increasing radiolucencies. This has
      led to the development of alternative glenoid components for unconstrained total
      shoulder arthroplasty. Variations in component design include component shape,
      articular conformity, method of fixation, and material composition. The purposes
      of this presentation are to review the performance of the original Neer design,
      as well as other more recent glenoid designs, to identify factors that may
      influence the performance of glenoid components, and to provide a rationale for
      future changes in glenoid component design.

PMID- 15726073
TI  - Biomechanical evaluation of a novel glenoid design in total shoulder
      arthroplasty.
AB  - The amount of articular curvature mismatch providing optimal performance in total
      shoulder arthroplasty (TSA) is unknown. The objectives of this study were to
      quantify glenohumeral joint mechanics before and after TSA and to compare the
      performance of 3 glenoid components: (1) nonconforming, (2) conforming, and (3) a
      novel design featuring a conforming center extending into a nonconforming
      periphery. Six fresh-frozen cadaveric shoulders (mean age, 43 years) were
      mechanically tested on a custom apparatus by use of simulated muscle forces and a
      coordinate-measuring machine to determine joint kinematics. B-spline models of
      the natural and prosthetic articular surfaces were generated, and joint contact
      was computed by use of a proximity criterion. During both centered ( P = .02) and
      eccentric ( P = .05) loading protocols, glenoid contact migrated posteriorly in
      conforming implants. No statistical differences in kinematics and contact were
      found among the nonconforming design, the new design, and the natural joint.
      Therefore, adding a central region of conformity does not compromise the ability
      of nonconforming TSA components to reduce rim loading.

PMID- 15726074
TI  - Humeral head replacement versus total shoulder arthroplasty: clinical outcomes--a
      review.
AB  - Total shoulder replacement (TSR) has been shown to provide predictable pain
      relief and functional improvement in patients with glenohumeral degenerative
      arthritis and an intact rotator cuff. When compared with patients with humeral
      head replacement (HHR), those with TSR have been reported to have more stability,
      less pain, and increased motion. However, concerns regarding glenoid loosening
      and the subsequent possibility of a difficult revision with bony deficits have
      led many to favor HHR alone. Proponents of HHR regard the glenoid as the "weak
      link" in TSR and, when weighing their options, consider glenoid resurfacing to be
      too great a risk. The literature suggests that TSR is the best form of treatment
      for glenohumeral osteoarthritis, except in certain cases of insufficient glenoid
      bone stock and irreparable rotator cuff tears. Several recent clinical outcomes
      studies support this, as they have shown better results after TSR in comparison
      to HHR. Although the fear of radiographic glenoid component loosening is
      appropriate, evidence of clinical glenoid loosening is not very common.
      Currently, glenoid component design, in relation to its articulation with the
      humeral head, continues to grow and evolve as efforts are focused on changes to
      decrease the incidence of loosening. In addition, improved surgical techniques of
      cement pressurization may help to minimize glenoid loosening as well. Thus, it is
      reasonable to expect that the excellent results currently attainable with TSR may
      improve.

PMID- 15726075
TI  - Grammont reverse prosthesis: design, rationale, and biomechanics.
AB  - Combined destruction of the rotator cuff and the glenohumeral joint may lead to a
      painful and pseudo-paralyzed shoulder. In this situation a nonconstrained
      shoulder prosthesis yields a limited functional result or may even be
      contraindicated. Previous constrained prostheses (ball-and-socket or reverse ball
      and-socket designs) have failed because their center of rotation remained lateral
      to the scapula, which limited motion and produced excessive torque on the glenoid
      component, leading to early loosening. The reverse prosthesis designed by Paul
      Grammont, unlike any previous reverse ball-and-socket design, has introduced 2
      major innovations that have led to its success: (1) a large glenoid hemisphere
      with no neck and (2) a small humeral cup almost horizontally oriented with a
      nonanatomic inclination of 155 degrees, covering less than half of the
      glenosphere. This design medializes and stabilizes the center of rotation,
      minimizes torque on the glenoid component, and helps in recruiting more fibers of
      the anterior and posterior deltoid to act as abductors. Furthermore, the humerus
      is lowered relative to the acromion, restoring and even increasing deltoid
      tension. The Grammont reverse prosthesis imposes a new biomechanical environment
      for the deltoid muscle to act, thus allowing it to compensate for the deficient
      rotator cuff muscles. The clinical experience does live up to the biomechanical
      concept: the reverse prosthesis restores active elevation above 90 degrees in
      patients with a cuff-deficient shoulder. However, external rotation often remains
      limited, particularly in patients with an absent or fat-infiltrated teres minor.
      Internal rotation is also rarely restored after a reverse prosthesis. Failure to
      restore sufficient tension in the deltoid may result in prosthetic instability.
      The design does appear to protect against early loosening of the glenoid
      component, but impingement of the humeral cup on the scapular neck can lead to
      scapular notching and polyethylene wear. This is a cause for concern, especially
      as the notch is often more extensive than can be explained by impingement alone.
      Bony lysis of the scapula may also be related to a polyethylene granuloma.
      Further follow-up is required to ensure that loosening does not become a problem
      in the long term, and it has been recommended to limit its use to elderly
      patients, arguably those aged over 70 years. Despite these concerns, the reverse
      prosthesis, based on the biomechanical Grammont concept, offers a true surgical
      option in several situations where only limited possibilities were previously
      available: cuff tear arthrosis, persistent shoulder pseudo-paralysis due to a
      massive and irreparable cuff tear, severe fracture sequelae, prosthetic revision
      in a cuff-deficient shoulder, and tumor surgery. Finally, surgeons must be aware
      that results are less predictable and complication/revision rates are higher in
      revision surgery.

PMID- 15726076
TI  - Initial glenoid component fixation in "reverse" total shoulder arthroplasty: a
      biomechanical evaluation.
AB  - In patients with rotator cuff arthropathy, a "reverse" shoulder prosthesis
      resists glenohumeral subluxation and offers the potential for improved function.
      However, premature mechanical failure due to loosening is a concern with these
      devices. This in vitro study evaluates initial glenoid component fixation of 2
      uncemented "reverse" prostheses during physiologic loading and determines the
      relationship among lateral offset of the glenosphere, fixation method, and
      motion. To simulate an excellent glenoid bone stock, a polyurethane foam bone
      with similar material properties to that of the glenoid cancellous bone was used.
      Both lateral offset and peripheral screw type affected the magnitude of baseplate
      motion. Baseplate motion for Delta III components and Reverse Shoulder Prosthesis
      (RSP) components fixed with 5.0-mm captured screws were below the 150 mum of
      motion generally accepted as the threshold for bone ingrowth. Stable fixation was
      achieved for the RSP-neutral components despite a substantially (69%) greater
      moment at the baseplate-foam interface compared with the Delta III. Obtaining
      similar results in vivo is partially dependent on surgical placement of the
      peripheral screws and the patient's glenoid bone stock.

PMID- 15726077
TI  - Kinematics and constraint of total elbow arthroplasty.
AB  - Total elbow arthroplasty has been a valuable procedure for patients with
      rheumatoid arthritis, posttraumatic arthritis, osteoarthritis, and failed
      reconstructive procedures of the elbow. Many of the original designs were simple
      hinge joints, in which intrinsic complete constraint of the articulation
      predictably resulted in failure by loosening. Subsequently, the development of
      elbow prostheses diverged into 2 general types: loose hinge (linked) and
      resurfacing (unlinked). The main concern with such development is instability,
      which is attributable to numerous factors including prosthesis design, ligament
      integrity, and position of the prosthesis. A series of studies have been
      performed to examine the intrinsic constraint of various total elbow arthroplasty
      designs, as well as the joint laxity after implantation in cadaveric specimens.

PMID- 15726078
TI  - Stability of the elbow: osseous constraints.
AB  - The elbow is considered a complex joint, and thus the elements contributing to
      stability of the elbow are no less intricate. The soft-tissue and articular
      surfaces that provide stability to the elbow share the capacity as a function of
      joint position and loading configuration. The issue of soft-tissue constraints is
      dealt with elsewhere in this volume, and the focus of this discussion is that of
      the articular contributions. In this context, the radial head is defined as a
      secondary stabilizer to resist valgus force. The coronoid is clearly the most
      important articular stabilizer of this joint.

PMID- 15726079
TI  - Soft-tissue stabilizers of the elbow.
AB  - Elbow stability is afforded by both static and dynamic structures. Static
      structures include the complex bony architecture and soft-tissue stabilizers.
      Knowledge of the anatomy and biomechanics of the stabilizers is important to
      understand, diagnose, and treat elbow instability. Bony anatomy, detailed
      elsewhere, contributes to the inherent stability of the elbow. The static soft
      tissue stabilizers consist of the anterior and posterior joint capsule and both
      medial and lateral collateral ligament complexes. Additional stability is
      conferred by dynamic structures--the muscles crossing the elbow joint.

PMID- 15726080
TI  - Optimizing stability in distal humeral fracture fixation.
AB  - Restoration of painless and satisfactory elbow function after a fracture of the
      distal humerus requires anatomic reconstruction of the articular surface,
      restitution of the overall geometry of the distal humerus, and stable fixation of
      the fracture fragments to allow early and full rehabilitation. Although these
      goals are now widely accepted by the orthopaedic community, they may be
      technically difficult to achieve, especially in the presence of substantial
      osteoporosis or comminution. Failure, when it occurs, typically occurs at the
      supracondylar level through loss of fixation in the distal fragments. To prevent
      such failure and thereby maximize the potential for union and full elbow mobility
      after a severely fractured distal humerus, 2 principles must be satisfied: (1)
      fixation in the distal fragment must be maximized and (2) all fixation in distal
      fragments should contribute to stability between the distal fragments and the
      shaft. There are 8 technical objectives by which these principles are met: (1)
      every screw in the distal fragments should pass through a plate; (2) engage a
      fragment on the opposite side that is also fixed to a plate; (3) as many screws
      as possible should be placed in the distal fragments; (4) each screw should be as
      long as possible; (5) each screw should engage as many articular fragments as
      possible; (6) the screws in the distal fragments should lock together by
      interdigitation, creating a fixed-angle structure; (7) plates should be applied
      such that compression is achieved at the supracondylar level for both columns;
      and (8) the plates must be strong enough and stiff enough to resist breaking or
      bending before union occurs at the supracondylar level. These can be achieved
      with parallel plating. Severe metaphyseal comminution and bone loss are managed
      by supracondylar shortening. From the biomechanical data in the literature, 3
      conclusions can be reached concerning fixation of distal humeral fractures.
      First, the concept that plates need to be placed perpendicular (90 degrees /90
      degrees orientation) is unsubstantiated and incorrect. Second, parallel placement
      of 2 plates in the sagittal plane is as strong or stronger than the 90 degrees
      /90 degrees orientation. Finally, linking the plates together through the bone,
      thereby creating the architectural equivalent of an arch, offers the greatest
      biomechanical stability for comminuted distal humeral fractures. This can be done
      by interdigitating and locking the screws together as they pass through the
      distal fragments from the medial and lateral plates placed in the sagittal plane.

PMID- 15726081
TI  - Type II SLAP lesions: a new scoring system--the sulcus score.
AB  - A new scoring system-the sulcus score-was developed to differentiate between a
      large superior labral sulcus and a type II superior labrum anterior-posterior
      (SLAP) lesion. The sulcus scoring system permits quantification of the size of
      the superior labral sulcus and the severity of a type II SLAP lesion.
      Specifically, the depth of the superior labral sulcus was classified into 4
      grades, and the length was recorded by clock position. The sulcus score was then
      calculated by multiplying the depth (grade) by the length (the number of "hours"
      from the clock position). After stretching of the anterior capsule into excessive
      humeral external rotation at 60 degrees glenohumeral abduction, the sulcus score
      of cadaveric shoulders increased significantly (before, 3.4; after, 6.8),
      indicating the extension of the superior labral sulcus and resulting in a
      pathologically created type II SLAP lesion. The intraclass correlation
      coefficient and mean difference were 0.77 and 0.8 +/- 0.7, respectively, for
      intraobserver repeatability and 0.72 and 0.9 +/- 0.6, respectively, for
      interobserver reproducibility. The sulcus score provided a consistent and
      objective means for quantitatively describing the size and severity of type II
      SLAP lesions. Clinical assessment of the superior labral sulcus by use of the
      sulcus score may be useful for the diagnosis and treatment of type II SLAP
      lesions.

PMID- 15726082
TI  - Kinematics and stability of the fractured and implant-reconstructed radial head.
AB  - Controversy exists as to the optimal management of radial head fractures.
      Biomechanical studies have been conducted to quantify elbow stability for
      simulated wedge fractures, head excision, and head replacement, with and without
      the integrity of the collateral ligaments. Our in vitro studies have demonstrated
      that in the ligamentously intact elbow, kinematics and stability are slightly
      altered with simulated depressed wedge fractures up to 120 degrees of the radial
      head, markedly altered with head resection, and improved after radial head
      replacement. Radial head excision decreases elbow stability in the ligament
      deficient elbow, and radial head replacement improves stability similar to that
      of the native radial head. The ligaments have the most marked influence on
      stability, particularly when the upper limb is positioned such that valgus and
      varus gravity loads are applied to the elbow. Whereas the radial head acts as a
      secondary stabilizer to the collateral ligaments with the arm in these positions,
      its relative role is greater when the arm is in the dependent position and elbow
      flexion is simulated, particularly in extension. Further studies are needed to
      elucidate the complex interaction of the radial head with the capitellum, the
      ulnohumeral joint, and the ligamentous structures for different activities of
      daily living.

PMID- 15726083
TI  - Pathomechanics of acquired shoulder instability: a basic science perspective.
AB  - Normal asymptomatic glenohumeral motion is dependent on the coordinated function
      of dynamic and static stabilizers. Data from both selective sectioning studies of
      the capsuloligamentous components and tensile testing of the inferior
      glenohumeral ligament have provided important insights into the in situ function
      of these structures. However, little is known regarding the mechanism of
      microdamage accumulation in acquired shoulder instability. Recent findings
      suggest that cyclic subfailure loading of the inferior glenohumeral ligament may
      induce gradual stretching of the anteroinferior capsule, compromising its
      capacity to restrain excessive humeral translations. Further studies elucidating
      the mechanism of load transmission in the capsule during physiologic arm motion,
      as well as data on the intrinsic healing response of the capsular ligaments, are
      required to more fully characterize the pathoetiology of acquired shoulder
      instability.

PMID- 15726084
TI  - Stress and strain in the anterior band of the inferior glenohumeral ligament
      during a simulated clinical examination.
AB  - The objective of this research was to predict, with a finite-element model, the
      stress and strain fields in the anterior band of the inferior glenohumeral
      ligament (AB-IGHL) during application of an anterior load with the humerus
      abducted. The stress and strain in the AB-IGHL were determined during a simulated
      simple translation test of a single intact shoulder. A 6-degree-of-freedom
      magnetic tracking system was used to measure the kinematics of the humerus with
      respect to the scapula. A clinician applied an anterior load to the humerus until
      a manual maximum was achieved at 60 degrees of glenohumeral abduction and 0
      degrees of flexion/extension and external rotation. For the computational
      analysis, the experimentally measured joint kinematics were used to prescribe the
      motion of the humerus with respect to the scapula, whereas the material
      properties of the AB-IGHL were based on published experimental data. The geometry
      of the AB-IGHL, humerus, and scapula was acquired by use of a volumetric computed
      tomography scan, which was used to define the reference configuration of the AB
      IGHL. Strains reached 12% along the inferior edge and 15% near the scapular
      insertion site at the position of maximum anterior translation. During this
      motion, the AB-IGHL wrapped around the humerus and transferred load to the bone
      via contact. Predicted values for von Mises stress in the ligament reached 4.3
      MPa at the point of contact with the humeral head and 6.4 MPa near the scapular
      insertion site. A comparison of these results to the literature suggests that the
      computational approach provided reasonable predictions of fiber strain in the AB
      IGHL when specimen-specific geometry and kinematics with average material
      properties were used. The complex stress and strain distribution throughout the
      AB-IGHL suggests that the continuous nature of the glenohumeral capsule should be
      considered in biomechanical analyses. In the future, this combined experimental
      and computational approach will be used for subject-specific studies of capsular
      function and could provide quantitative data to help surgeons improve methods for
      the diagnosis and treatment of glenohumeral instability.

PMID- 15726085
TI  - Stability and instability of the glenohumeral joint: the role of shoulder
      muscles.
AB  - Shoulder muscles contribute to both mobility and stability of the glenohumeral
      joint. To improve treatments for shoulder instability, we focused on the
      contribution of the shoulder muscles to glenohumeral joint stability in
      clinically relevant positions. Both computational and experimental models were
      used. A computational model of the glenohumeral joint quantified stability
      provided by active muscle forces in both mid-range and end-range glenohumeral
      joint positions. Compared with mid-range positions, the resultant joint force at
      end-range positions was more anteriorly directed, indicating that its
      contribution to glenohumeral joint stability was diminished. In end-range
      positions, simulated increases in rotator cuff muscle forces tended to improve
      stability whereas increases in deltoid or pectoralis major muscle forces tended
      to further decrease stability. To validate these results, a cadaveric model,
      simulating relevant shoulder muscles, was used to quantify glenohumeral joint
      stability. When infraspinatus muscle activity was decreased, compressive forces
      decreased. When pectoralis major muscle activity was increased, anteriorly
      directed forces increased. If anteriorly directed forces increase or compressive
      forces decrease, stability of the glenohumeral joint decreases. This cadaveric
      model was then used to evaluate the effect of placing the joint in the
      apprehension position of abduction, external rotation, and horizontal abduction.
      Consistent with the results of our computational model, apprehension positioning
      increased anteriorly directed forces. Knowledge gained from these models was then
      used to develop a cadaveric model of glenohumeral joint dislocation. Dislocation
      resulted from the mechanism of forcible apprehension positioning when the
      appropriate shoulder muscles were simulated and a passive pectoralis major muscle
      was included. Capsulolabral lesions resulted that were similar to those observed
      in vivo. Shoulder muscle forces are usually powerful stabilizers of the
      glenohumeral joint, especially in mid-range positions when the passive
      stabilizers are lax. However, muscle forces can contribute to instability as
      well. Certain muscle forces decrease glenohumeral joint stability in end-range
      positions. We found this to be the case with both active and passive pectoralis
      major forces. Improved understanding of the contribution of muscle forces not
      only toward stability but also toward instability will improve rehabilitation
      protocols for the shoulder and prove useful in the treatment of joint instability
      throughout the body.

PMID- 15726086
TI  - External rotation of the glenohumeral joint: ligament restraints and muscle
      effects in the neutral and abducted positions.
AB  - External rotation of the glenohumeral joint is important in a variety of
      pathologic states, yet the ligamentous restraints to external rotation have not
      been thoroughly investigated and the muscle effects have received even less
      attention. The purpose of this study was to investigate the ligamentous
      restraints and muscle effects limiting external rotation of the glenohumeral
      joint in a biomechanical cadaveric model. External rotation torque was applied to
      the humeri of 15 shoulders mounted in the supine position in a custom fixture
      while varying rotator cuff and biceps loads in 15 degrees and 60 degrees of
      glenohumeral abduction. A randomly chosen ligament (coracohumeral ligament [CHL],
      combined superior and middle glenohumeral ligaments [S+M], anterior band of the
      inferior glenohumeral ligament [AB], entire inferior glenohumeral ligament
      [IGHL], or posterior capsule [PC]) was cut, and testing was repeated (n = 3 for
      each ligament). Torque data were collected every 3 degrees through the entire
      range of external rotation. Individual muscles were loaded with 22.2 N
      (designated as a standard state) and were compared with loads of 0, 11.1, and
      44.5 N. Alterations in muscle loads were analyzed with a residual maximum
      likelihood-based repeated-measures model. Ligament effects were analyzed by use
      of analysis of variance with Tukey correction. In the neutral position, each
      ligament except the PC significantly affected the torque required for external
      rotation, with IGHL > CHL > AB > S+M. In this position, loading the subscapularis
      to 44.5 N significantly increased the torque required to externally rotate the
      shoulder whereas unloading it significantly decreased the torque required. In the
      60 degrees abducted position, each ligament except the PC significantly affected
      the torque required for external rotation, with IGHL > AB > S+M > CHL. In this
      position, loading the biceps or subscapularis to 44.5 N significantly increased
      the torque required to externally rotate the shoulder as rotation increased
      whereas unloading it significantly decreased the torque required as rotation
      increased. This work demonstrates that the glenohumeral joint capsule behaves as
      a cylinder with many regions serving as restraints to external rotation. In
      addition, the long head of the biceps has an important role as a dynamic
      restraint to external rotation in the abducted shoulder. This is a new function
      attributed to the biceps and reinforces the role of external rotation in the
      generation of biceps and superior labral pathology.

PMID- 15726087
TI  - Development of cadaveric models of a thrower's shoulder.
AB  - Two novel cadaveric models of a thrower's shoulder were evaluated. Both models
      included the capsuloligamentous and osseous components of the glenohumeral joint.
      In model 1 the coracohumeral ligament was retained and the glenoid was positioned
      parallel to the ground whereas the humerus was positioned at 60 degrees of
      glenohumeral elevation in the scapular plane. In model 2 the coracohumeral
      ligament was resected and the glenoid was positioned vertically at 30 degrees of
      scapular elevation whereas the humerus was positioned at 60 degrees of
      glenohumeral elevation in the scapular plane. Each specimen was sequentially
      tested under 3 conditions: intact, after nondestructive anterior capsular
      stretch, and after simulated posterior capsular contracture. Measurements
      included rotational range of motion and relative glenohumeral position from
      neutral to maximum external rotation of the humerus. In model 2 the glenohumeral
      forces were also measured by use of a 6-degree-of-freedom load cell. The
      stretching of the anterior capsule in model 1 was performed while the humeral
      head was constrained in the glenoid and in model 2 while the humeral head was
      unconstrained. Both models showed increased humeral external rotation and
      decreased humeral internal rotation similar to that seen in throwing athletes.
      Both models also showed an increased humeral shift inferiorly after anterior
      capsular stretching. Model 1 demonstrated a subsequent humeral shift superiorly
      after posterior capsule plication. Unconstrained specimens of model 2 dislocated
      posteriorly and inferiorly after posterior capsule plication when the humerus was
      rotated to maximum external rotation. On the basis of these findings, for future
      studies, constrained capsular stretching models will be further investigated.

PMID- 15726088
TI  - Effect of rotator cuff pathology on shoulder rhythm.
AB  - The purpose of this study was to test the hypothesis that shoulder rhythm is
      affected by rotator cuff pathology during arm elevation. We divided 42 subjects
      into 3 groups: those with full-thickness rotator cuff tears (RCTs) (n = 14),
      those with tendinopathy (n = 13), and control subjects (n = 15). Shoulder
      kinematics was recorded while subjects performed elevation in the sagittal and
      scapular planes. Euler angles were computed for scapular and humeral elevation.
      Data were divided into 3 equal phases. Lines were fit and the slope determined
      for each phase. Significant differences in slopes ( P < .05) were found between
      experimental groups for both motions. The RCT group had higher slopes in the
      initial and middle phases for sagittal elevation and in the middle phase for
      scapular abduction. The scapula was elevated more in the RCT group in the initial
      two thirds of movement. This motion may change the length of remaining muscles so
      that they operate on a more effective part of their length-tension curve.

PMID- 15726089
TI  - Biomechanical effects of supraspinatus repair on the glenohumeral joint.
AB  - We repaired full-thickness rotator cuff tears in human cadaveric shoulder
      specimens. The purpose of this study was to determine whether a repaired
      supraspinatus will result in a change in joint forces, contact pressures and
      area, and position of the humerus relative to the glenoid compared with the
      pathologic and simulated complete-tear specimens. Force couples exist in the
      coronal plane between the deltoid and the inferior portion of the rotator cuff
      and in the transverse plane between the anterior cuff (subscapularis) and
      posterior cuff (infraspinatus and teres minor). This has served as a model for
      shoulder and rotator cuff research. Our model differs from previous studies in
      that the pectoralis major and latissimus dorsi/teres major were included because
      they are important contributors to shoulder function. Muscle force simulation was
      performed through a clamp, cable, and pneumatic system for the tendons of the
      rotator cuff, pectoralis major, and teres major/latissimus dorsi. Each specimen
      was tested in its native state of a full-thickness supraspinatus tear in 10
      degrees and 60 degrees of abduction with neutral humeral rotation. In each
      position there were 2 loading conditions: (1) all muscles loaded with 60 N and
      (2) deltoid loaded with 90 N and 60 N for all others (3:2 ratio between the
      deltoid and supraspinatus). Pathologic tear, repaired, and simulated complete
      tear conditions were subjected to the same testing sequence. After repair, there
      was an increase in percent inferior force in the 10 degrees abduction, 60-N
      loaded condition ( P = .02). The increase in percent inferior force may represent
      greater concavity-compression and spacer effect, which are both important
      functions of the supraspinatus. Contact pressure decreased in both the pathologic
      and simulated complete-tear conditions at 10 degrees abduction with 90-N deltoid
      loading ( P = .01). A corresponding increase in area was observed at this
      position for the pathologic tear condition only ( P = .01). This could represent
      greater concavity-compression, indicating that strengthening may provide a
      biomechanical benefit.

PMID- 15726090
TI  - Supraspinatus tendon composition remains altered long after tendon detachment.
AB  - Most rotator cuff surgery is performed on chronic tears, but changes in the
      composition of chronically torn tendons remain poorly understood. In this study
      we surgically created supraspinatus tears in the rat and analyzed the composition
      of the tendon over time using immunohistochemistry. We found that collagen types
      I and XII were greatly increased initially after injury and then decreased with
      time. Collagen type III was detected and persisted in the scar for months.
      Decorin and biglycan were increased initially and then decreased, although
      decorin remained elevated from normal for months after injury. Aggrecan and
      collagen type II were detected in small amounts after detachment, which was
      associated with the expression of sulfated glycosaminoglycans. These alterations
      were similar to those seen in human studies. As the quality of the tendon is an
      important factor in repair, these findings may partially explain why chronic
      tears heal differently than acute tears.

PMID- 15726091
TI  - Inflammatory and angiogenic mRNA levels are altered in a supraspinatus tendon
      overuse animal model.
AB  - Shoulder overuse injuries, especially those to the supraspinatus tendon of the
      rotator cuff, are common musculoskeletal disorders. Unfortunately, little is
      known about the disease etiology and pathogenesis. The objective of this study
      was to determine the levels of specific inflammatory and angiogenic markers in a
      rat supraspinatus tendon overuse injury model. We hypothesized that inflammation
      would not be present early in the overuse protocol. Conversely, we hypothesized
      that the overuse protocol would result in increased angiogenesis early. Increases
      in five-lipoxygenase activating protein, cyclooxygenase-2, vascular endothelial
      growth factor, and von Willebrand factor were evaluated by use of reverse
      transcription-polymerase chain reaction from 1 day through 16 weeks of treadmill
      running (overuse protocol). These results provide important information on the
      role of angiogenesis and inflammation in the disease process. Future studies will
      further evaluate the mechanisms of the disease process as well as potential
      targeted treatment modalities.

PMID- 15726092
TI  - The molecular pathophysiology of subacromial bursitis in rotator cuff disease.
AB  - Little information exists on the molecular and biochemical pathophysiology of
      subacromial bursitis and rotator cuff disease. We investigated the pattern of
      expression of cytokines (interleukin [IL]-1beta, IL-1, IL-6, tumor necrosis
      factor [TNF] alpha, small inducible cytokines), metalloproteases, and
      cyclooxygenases in the subacromial bursa in patients with rotator cuff disease.
      Subacromial bursa specimens were prepared for molecular and biochemical analysis
      in patients undergoing shoulder surgery following an institutional review board
      approved protocol. Specimens were analyzed for the presence of cytokines,
      metalloproteases, and cyclooxygenases by use of microarray for gene expression
      and immunohistocytochemistry. Microarray analysis for gene expression and
      immunohistochemistry demonstrated that the expression of several cytokine genes
      (TNF, IL-1alpha, IL-1beta, and IL-6) was increased in patients with subacromial
      bursitis compared with control specimens. Furthermore, the expression of
      metalloproteases (MMP-1 and MMP-9) and cyclooxygenases (COX-1 and COX-2) in the
      bursitis group was found to be increased as compared with controls. Although
      further investigation is required, these studies suggest that inflammation of the
      subacromial bursa does occur in patients with rotator cuff disease. These
      findings support the role of anti-inflammatory agents in the treatment of
      subacromial impingement and emphasize the importance of subacromial bursectomy to
      reduce inflammation in rotator cuff disease.

PMID- 15726093
TI  - Development of a Flexilevel Scale for use with computer-adaptive testing for
      assessing shoulder function.
AB  - In a 5-year study, a self-report measure of shoulder function-the Flexilevel
      Scale of Shoulder Function (FLEX-SF)-was developed by use of item response
      theory. A large pool of candidate items (N = 68) was developed. A questionnaire
      that included the 68 items, another scale of shoulder function, and clinical and
      demographic questions were administered to 400 persons with shoulder complaints.
      Patients' responses to the 68 items were calibrated by use of Andrich's rating
      scale model. Thirty-three items were selected from the pool and subdivided into
      three overlapping testlets targeting low, medium, and high shoulder function. A
      table translates raw scores on testlets to a common mathematical metric. The
      validity and reliability of the FLEX-SF was evaluated in a longitudinal study of
      199 patients. The FLEX-SF scores were highly reliable and exhibited excellent
      validity (including responsiveness). We report on a simulation of a computer
      adaptive test of shoulder function. This simulation is based on the developmental
      items we tested for use in the FLEX-SF. The results indicate that greater
      measurement efficiency can be achieved with a computer-adaptive test format.

PMID- 15726094
TI  - The relationship among strength and mobility measures and self-report outcome
      scores in persons after rotator cuff repair surgery: impairment measures are not
      enough.
AB  - In the past, measures of active range of motion and strength testing were deemed
      sufficient to "prove" the efficacy of treatment interventions. In the current
      outcomes milieu, however, the focus has shifted to patient-centered assessment
      (ie, patients' ability to perform activities that are personally relevant). We
      report results from a study with patients in the private practice of a shoulder
      surgeon. In this study we evaluated the relationship between impairment measures
      and scores from several shoulder outcome scales. In addition, we examined
      transcripts of interviews with shoulder patients regarding the impact of shoulder
      problems on their lives. One hundred eight persons participated in a randomized
      trial of home exercise instruction after arthroscopic repair of rotator cuff
      tears. Two impairment measures were used-strength estimates obtained by use of a
      Nicholas electronic dynamometer and range of motion in the standing position.
      Self- reported outcomes were measured by use of the Shoulder Pain and Disability
      Index (SPADI) and the University of Pennsylvania (UPenn) Shoulder Scale. Pearson
      correlation coefficients were calculated to estimate the associations between
      scores on impairment measures and self-report measures. R 2 values were
      calculated to estimate the proportion of variance shared by impairment and self
      report scores. We found that the linear relationship between impairment scores
      and patient-reported outcomes was quite low, explaining as little as 8% of the
      total variance. Qualitative analysis of patient interviews suggests that patients
      distinguish between their impairment and their status on personally relevant
      outcomes. Future research should evaluate the nature of patient judgments of
      shoulder health outcomes.

PMID- 15726095
TI  - Proximal humeral anatomy in shoulder arthroplasty: Implications for prosthetic
      design and surgical technique.
AB  - Resurfacing arthroplasty of the glenohumeral joint has been established for
      several decades as a means to restore comfort and function of the shoulder for
      many afflictions that derange the normal anatomy. Rigorous study of shoulder
      anatomy in terms relevant to prosthetic geometry, however, did not begin until
      the 1990s. It has become apparent that normal anatomy is highly variable from
      individual to individual and that it is aligned somewhat differently than the
      early modular prosthetic devices. Multiple studies have shown that retroversion
      is markedly variable, not only between individuals but also between the left and
      right sides of the same individual, ranging from 0 degrees to 55 degrees . The
      inclination of the proximal humeral articular surface relative to the shaft (head
      shaft angle) is also variable, ranging from 30 degrees to 55 degrees. The center
      of rotation is variably offset in 3 dimensions. The radius of curvature ranges
      from 20 to 30 mm and is smaller in women than in men. The thickness of the
      articular surface, head height, is equally variable but shows a striking
      proportionality to the radius of curvature. The last decade has seen a
      proliferation of humeral implants aiming to serve a better understanding of
      shoulder anatomy and function. A modern understanding of shoulder anatomy and
      contemporary design features is paramount for surgeons performing shoulder
      arthroplasty. Head size selection is dependent on multiple factors, the most
      important of these, other than the patient's original head size, are the
      osteotomy performed by the surgeon and the inclination angle(s) of the prosthetic
      system. Systems with variable inclination angles instruct the surgeon to resect
      the humeral head along the anatomic neck as best possible and then provide either
      adjustable or variable prosthetic geometries to match the resultant inclination
      angle. Other prosthetic systems have a fixed inclination angle somewhere within
      the normal range and instruct the surgeon to make an osteotomy at this
      inclination, adjusting the fit with additional preparation of the canal and
      revising the osteotomy as necessary. Over the last decade, most systems have
      offered heads that are offset by 3 to 4 mm, allowing the surgeon to dial in the
      most suitable position for the head on the stem. Component design and surgical
      technique are inextricably intertwined. Most surgeons with experience using
      modern systems feel a greater sense of predictability in achieving their surgical
      goals when using these systems as compared with earlier ones. How these
      developments impact implant longevity will only be known with time and further
      follow-up.

PMID- 15726096
TI  - Identification of genes associated with platinum drug sensitivity and resistance
      in human ovarian cancer cells.
AB  - Platinum-based chemotherapeutic regimens are ultimately unsuccessful due to
      intrinsic or acquired drug resistance. Understanding the molecular basis for
      platinum drug sensitivity/resistance is necessary for the development of new
      drugs and therapeutic regimens. In an effort to identify such determinants, we
      evaluated the expression of approximately 4000 genes using cDNA microarray
      screening in a panel of 14 unrelated human ovarian cancer cell lines derived from
      patients who were either untreated or treated with platinum-based chemotherapy.
      These data were analysed relative to the sensitivities of the cells to four
      platinum drugs (cis-diamminedichloroplatinum (cisplatin), carboplatin, DACH
      (oxalato)platinum (II) (oxaliplatin) and cis-diamminedichloro (2-methylpyridine)
      platinum (II) (AMD473)) as well as the proliferation rate of the cells.
      Correlation analysis of the microarray data with respect to drug sensitivity and
      resistance revealed a significant association of Stat1 expression with decreased
      sensitivity to cisplatin (r=0.65) and AMD473 (r=0.76). These results were
      confirmed by quantitative RT-PCR and Western blot analyses. To study the
      functional significance of these findings, the full-length Stat1 cDNA was
      transfected into drug-sensitive A2780 human ovarian cancer cells. The resulting
      clones that exhibited increased Stat1 expression were three- to five-fold
      resistant to cisplatin and AMD473 as compared to the parental cells. The effect
      of inhibiting Jak/Stat signalling on platinum drug sensitivity was investigated
      using the Janus kinase inhibitor, AG490. Pretreatment of platinum-resistant cells
      with AG490 resulted in significant increased sensitivity to AMD473, but not to
      cisplatin or oxaliplatin. Overall, the results indicate that cDNA microarray
      analysis may be used successfully to identify determinants of drug
      sensitivity/resistance and future functional studies of other candidate genes
      from this database may lead to an increased understanding of the drug resistance
      phenotype.

PMID- 15726098
TI  - The preferences of 600 patients for different descriptions of randomisation.
AB  - A total of 600 patients from cancer centres throughout the UK identified their
      most preferred and most disliked descriptions of randomisation found in current
      patient information sheets and websites. The CancerBACUP description, which
      describes both the process of randomisation and why it is done, was most
      preferred 151 out of 533 (28%) patients. The NCI description was viewed as overly
      technical and most disliked 185 out of 483 (38%) patients.

PMID- 15726097
TI  - Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in
      advanced gastric cancer.
AB  - We conducted this study to ascertain the efficacy and toxicity of docetaxel and
      cisplatin combined with oral UFT and leucovorin as a first-line treatment for
      patients with advanced gastric cancer. In all, 52 patients received courses of
      docetaxel 60 mg m(-2) intravenously (i.v.) for 1 h and then cisplatin 75 mg m(-2)
      i.v. for 2 h on day 1. Oral UFT at 400-600 mg day(-1), as determined by body
      surface area, and leucovorin at 75 mg day(-1) were administered for 21
      consecutive days from day 1, and this was followed by a 7-day drug-free interval.
      A total of 225 courses were administered, and the median number of courses per
      patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%)
      were achieved, giving an overall response rate of 50% (95% Confidence Interval:
      36.4-63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36
      patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients
      (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median
      survival duration was 48 weeks (4 to 156+ weeks), and median response duration
      was 24 weeks (6-152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and
      leucovorin combination chemotherapy is effective and tolerable for the treatment
      of advanced gastric cancer.

PMID- 15726099
TI  - Influence of folate status on genomic DNA methylation in colonic mucosa of
      subjects without colorectal adenoma or cancer.
AB  - DNA hypomethylation may increase the risk of colorectal cancer. The main aim of
      this study was to assess the influence of folate status (serum and erythrocyte
      folate and plasma homocysteine concentrations) on DNA methylation.
      Methylenetetrahydrofolate reductase (MTHFR 677C --> T and 1298A --> C),
      methionine synthase (MS 2756A --> G) and cystathionine synthase (CBS 844ins68)
      polymorphisms were measured to account for potential confounding effects on
      folate status and DNA methylation. A total of 68 subjects (33 men and 35 women,
      36-78 years) free from colorectal polyps or cancer were recruited in a cross
      sectional study. Tissue biopsies were obtained at colonoscopy for the
      determination of DNA methylation in colonic mucosa using an in vitro
      radiolabelled methyl acceptance assay. Serum and erythrocyte folate were
      inversely correlated with plasma homocysteine (r=-0.573, P<0.001 and r=-0.307,
      P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=-0.311, P=0.01
      and r=-0.356, P=0.03). After adjusting for gender, age, body mass index, smoking
      and genotype, there were weak negative associations between serum and erythrocyte
      folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively).

PMID- 15726100
TI  - Mutagenicity of comfrey (Symphytum Officinale) in rat liver.
AB  - Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and
      herbal remedy by humans. In order to evaluate the mechanisms underlying its
      carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big
      Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and
      the types of mutations induced by comfrey suggest that its tumorigenicity results
      from the genotoxicity of pyrrolizidine alkaloids in the plant.

PMID- 15726101
TI  - An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii
      pneumonia in patients with malignancy receiving corticosteroid therapy at a
      cancer hospital.
AB  - Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in
      immunocompromised patients without human immunodeficiency virus infection.
      However, chemoprophylaxis is highly effective. In patients with solid tumours or
      haematologic malignancy, several risk factors for developing PCP have been
      identified, predominantly corticosteroid therapy. The aims of this study were to
      identify the potentially preventable cases of PCP in patients receiving
      corticosteroid therapy at a tertiary care cancer centre and to estimate the
      frequency of utilisation of chemoprophylaxis in these patients. Two retrospective
      reviews were performed. Over a 10-year period, 14 cases of PCP were identified:
      no cases were attributable to failed chemoprophylaxis, drug allergy or
      intolerance. During a 6-month period, 73 patients received high-dose
      corticosteroid therapy (> or =25 mg prednisolone or > or =4 mg dexamethasone
      daily) for > or =4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51
      (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis
      compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001).
      Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or
      solid tumours who receive corticosteroid therapy are proposed. Successful primary
      prevention of PCP in this population will require a multifaceted approach
      targeting the suboptimal prescribing patterns for chemoprophylaxis.

PMID- 15726102
TI  - Randomised controlled trial of mammographic screening in women from age 40:
      results of screening in the first 10 years.
AB  - Debate continues over the effectiveness of screening by mammography in women
      below age 50. We report here on results of screening in the first 10 years of a
      randomised trial to study the effect on breast cancer mortality of invitation to
      annual mammography from age 40 to 41 compared to first invitation to the 3-yearly
      UK national programme at age 50-52. The trial is taking place in 23 NHS breast
      screening centres. Between 1991 and 1997, 160 921 women were randomised in the
      ratio 1 : 2 to intervention and control arms. Screening is by two views at first
      screen and single view subsequently; data on screening up to and including round
      five are now complete. Uptake of invitation to screening is between 68 and 70% at
      all but the latest screening rounds. Rates of referral for assessment are 4.6% at
      first screen and 3.4% at subsequent screens. Invasive cancer detection rates are
      0.09% at first screen, and similar at rescreens until the sixth and later
      screens. There is little evidence of regular mammography in the trial control
      arm. The setting of this trial within the NHS breast screening programme should
      ensure applicability of results to a national programme.

PMID- 15726103
TI  - Randomised controlled trial of mammographic screening in women from age 40:
      predicted mortality based on surrogate outcome measures.
AB  - A trial in the UK to study the effect on mortality from breast cancer of
      invitation for annual mammography from the age of 40-41, has randomised a total
      of 160 921 women in the ratio 1 : 2 to the intervention and control arms. All
      breast cancers diagnosed in the two arms have been identified, and the histology
      reviewed. This paper presents the results of an interim analysis using surrogate
      outcome measures to compare predicted breast cancer mortality in the two arms
      based on 1287 cases diagnosed to 31.12.1999. Due to earlier diagnosis, there is
      currently an 8% excess of invasive breast cancers in the intervention arm. The
      ratio of predicted deaths at 10 years in the intervention arm relative to the
      control arm, adjusted for this excess diagnosis, ranges from 0.89 (95% confidence
      interval (CI) 0.78-1.01) to 0.90 (95% CI 0.80-1.01). Screening from age 40 may
      result in a lower reduction in breast cancer mortality than that observed in
      other trials including women below age 50. This analysis based on surrogate
      outcome measures suggests that a reduction in breast cancer mortality may be
      observed in this trial. However, a number of assumptions have been necessary and
      firm conclusions must await the analysis of observed mortality from breast
      cancer.

PMID- 15726104
TI  - Further evidence for an HLA-related recessive mutation in nasopharyngeal
      carcinoma among the Chinese.
AB  - We typed 247 cases of nasopharyngeal carcinoma (NPC), a disease predominantly of
      the southern Chinese, and 274 controls from the Chao Shan region of China's
      Guangdong province for HLA A and B. Besides confirming the established
      associations with A2, A33, B46 and B58 (positive associations) and A11 (negative
      association), the results demonstrated a number of rarer alleles with strong
      negative association with NPC. Our data, combined with those from the previous
      studies in Southern Chinese, displayed the protective effects for A31 (odds ratio
      (OR)=0.0; 95% confidence interval (CI)=0-0.11), B13 (OR=0.50; 95% CI=0.35-0.69),
      B27 (OR=0.49; 95% CI=0.25-0.92), B39 (OR=0.18; 95% CI=0.06-0.48) and B55
      (OR=0.32; 95% CI=0.14-0.68), the ORs comparing individuals with or without each
      allele. Other ethnic groups do not display such large HLA-associated variation in
      NPC risk. We show that a linked NPC gene with dominant mode of action could not
      generate such large protective effects. The results provide strong supporting
      evidence for the existence of a southern Chinese specific, recessive NPC gene
      closely linked to the HLA region as a major determinant of the Chinese risk for
      the disease.

PMID- 15726105
TI  - Ascitic complement system in ovarian cancer.
AB  - Ovarian cancer spreads intraperitoneally and forms fluid, whereby the diagnosis
      and therapy often become delayed. As the complement (C) system may provide a
      cytotoxic effector arm for both immunological surveillance and mAb-therapy, we
      have characterised the C system in the intraperitoneal ascitic fluid (AF) from
      ovarian cancer patients. Most of the AF samples showed alternative and classical
      pathway haemolytic activity. The levels of C3 and C4 were similar to or in the
      lower normal range when compared to values in normal sera, respectively. However,
      elevated levels of C3a and soluble C5b-9 suggested C activation in vivo.
      Malignant cells isolated from the AF samples had surface deposits of C1q and C3
      activation products, but not of C5b-9 (the membrane attack complex; MAC).
      Activation could have become initiated by anti-tumour cell antibodies that were
      detected in the AFs and/or by changes on tumour cell surfaces. The lack of MAC
      was probably due to the expression of C membrane regulators CD46, CD55 and CD59
      on the tumour cells. Soluble forms of C1 inhibitor, CD59 and CD46, and the
      alternative pathway inhibitors factor H and FHL-1 were present in the AF at
      concentrations higher than in serum samples. Despite the presence of soluble C
      inhibitors it was possible to use AF as a C source in antibody-initiated killing
      of ovarian carcinoma cells. These results demonstrate that although the ovarian
      ascitic C system fails as an effective immunological surveillance mechanism, it
      could be utilised as an effector mechanism in therapy with intraperitoneally
      administrated mAbs, especially if the intrinsic C regulators are neutralised.

PMID- 15726110
TI  - Exclusion of the dymeclin and PAPSS2 genes in a novel form of
      spondyloepimetaphyseal dysplasia and mental retardation.
AB  - Spondyloepimetaphyseal dysplasias (SEMD) represent a heterogeneous group of
      conditions composed of at least 15 well-defined entities. The classification is
      based on clinical, radiological and molecular findings. Among them, several
      conditions also include a mental retardation (MR) syndrome, namely Wolcott
      Rallison syndrome, Dyggve-Melchior-Clausen syndrome (DMC) and lysosomal storage
      disorders. Here, we report on a novel form of SEMD with MR in two Pakistani
      sisters born to first-cousin parents. SEMD, MR, microcephaly, ataxia, facial
      dysmorphism and hirsutism of back and legs were noted in the two children.
      Skeletal findings included flat vertebral bodies with irregular vertebral plates,
      irregular and flared metaphyses with vertical striations, small and irregular
      epiphyses, small carpal bones and narrow iliac wings without lacy pelvis iliac
      crest. Similarities with DMC prompted us to test and eventually exclude the DMC
      gene, dymeclin, by direct sequencing. Similarly, we excluded the PAPSS2 gene (3'
      alpha phosphoadenosine 5'-phosphosulphate synthase 2) responsible for SEMD
      Pakistani type. The combination of features observed in the two sisters does not
      fit with any previously reported SEMD and represents therefore a novel form of
      autosomal recessive SEMD with MR.

PMID- 15726111
TI  - Genetic Testing: from chromosomes to DNA, a revolution in prenatal diagnosis.

PMID- 15726112
TI  - Structure of allelic variants of subtype 5 of histone H1 in pea Pisum sativum L.
AB  - The pea genome contains seven histone H1 genes encoding different subtypes.
      Previously, the DNA sequence of only one gene, His1, coding for the subtype H1-1,
      had been identified. We isolated a histone H1 allele from a pea genomic DNA
      library. Data from the electrophoretic mobility of the pea H1 subtypes and their
      N-bromosuccinimide cleavage products indicated that the newly isolated gene
      corresponded to the H1-5 subtype encoded by His5. We confirmed this result by
      sequencing the gene from three pea lines with H1-5 allelic variants of altered
      electrophoretic mobility. The allele of the slow H1-5 variant differed from the
      standard allele by a nucleotide substitution that caused the replacement of the
      positively charged lysine with asparagine in the DNA-interacting domain of the
      histone molecule. A temperature-related occurrence had previously been
      demonstrated for this H1-5 variant in a study on a worldwide collection of pea
      germplasm. The variant tended to occur at higher frequencies in geographic
      regions with a cold climate. The fast allelic variant of H1-5 displayed a
      deletion resulting in the loss of a duplicated pentapeptide in the C-terminal
      domain.

PMID- 15726113
TI  - Evolution of the chromosomal location of rDNA genes in two Drosophila species
      subgroups: ananassae and melanogaster.
AB  - The evolution of the chromosomal location of ribosomal RNA gene clusters and the
      organization of heterochromatin in the Drosophila melanogaster group were
      investigated using fluorescence in situ hybridization and DAPI staining to
      mitotic chromosomes. The investigation of 18 species (11 of which were being
      examined for the first time) belonging to the melanogaster and ananassae
      subgroups suggests that the ancestral configuration consists of one nucleolus
      organizer (NOR) on each sex chromosome. This pattern, which is conserved
      throughout the melanogaster subgroup, except in D. simulans and D. sechellia, was
      observed only in the ercepeae complex within the ananassae subgroup. Both sex
      linked NORs must have been lost in the lineage leading to D. varians and in the
      ananassae and bipectinata complexes, whereas new sites, characterized by intra
      species variation in hybridization signal size, appeared on the fourth chromosome
      related to heterochromatic rearrangements. Nucleolar material is thought to be
      required for sex chromosome pairing and disjunction in a variety of organisms
      including Drosophila. Thus, either remnant sequences, possibly intergenic spacer
      repeats, are still present in the sex chromosomes which have lost their NORs (as
      observed in D. simulans and D. sechellia), or an alternative mechanism has
      evolved.

PMID- 15726115
TI  - Frontal glucose hypometabolism in abstinent methamphetamine users.
AB  - Changes in relative regional cerebral glucose metabolism (rCMRglc) and their
      potential gender differences in abstinent methamphetamine (MA) users were
      explored. Relative rCMRglc, as measured by (18)F-fluorodeoxyglucose positron
      emission tomography, and frontal executive functions, as assessed by Wisconsin
      card sorting test (WCST), were compared between 35 abstinent MA users and 21
      healthy comparison subjects. In addition, male and female MA users and their
      gender-matched comparison subjects were compared to investigate potential gender
      differences. MA users had lower rCMRglc levels in the right superior frontal
      white matter and more perseveration and nonperseveration errors in the WCST,
      relative to healthy comparison subjects. Relative rCMRglc in the frontal white
      matter correlated with number of errors in the WCST in MA users. In the
      subanalysis for gender differences, lower rCMRglc in the frontal white matter and
      more errors in the WCST were found only in male MA users, not in female MA users,
      relative to their gender-matched comparison subjects. The current findings
      suggest that MA use causes persistent hypometabolism in the frontal white matter
      and impairment in frontal executive function. Our findings also suggest that the
      neurotoxic effect of MA on frontal lobes of the brain might be more prominent in
      men than in women.

PMID- 15726114
TI  - Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior:
      inhibition by CRF1- and benzodiazepine-receptor antagonists and a 5-HT1a-receptor
      agonist.
AB  - Repeated withdrawals from chronic ethanol induce a persistent adaptive change.
      Further, stress substitutes for the initial two withdrawals of a multiple
      withdrawal protocol to sensitize rats to withdrawal-induced anxiety-like behavior
      ('anxiety'). Therefore, it was tested whether the persistent adaptation induced
      by multiple-withdrawal exposures allows stress to elicit anxiety after a period
      of abstinence. Social interaction was used to assess the degree of anxiety
      induced by 45 min of restraint stress 3, 7, or 14 days after rats were exposed to
      multiple withdrawals from a chronic 4.5% ethanol diet. Restraint stress reduced
      social interaction (ie anxiety-like behavior) at 3, but not at 7 or 14 days,
      after the multiple withdrawals. No anxiety response was observed in animals that
      received multiple withdrawals without stress or in animals that received stress
      when exposed only to control liquid diet. Drugs (ie a CRF1-receptor antagonist, a
      benzodiazepine receptor antagonist, and a 5-HT1A-receptor agonist) previously
      demonstrated to block the cumulative adaptation, when administered during
      repeated withdrawals, prevented stress-induced anxiety-like behavior during
      abstinence. Additionally, these drugs applied prior to stress in the rats
      previously exposed to the repeated withdrawal protocol, likewise, minimized
      stress-induced anxiety. The anxiety following stress during abstinence from
      previous chronic ethanol exposure is indicative of an interaction of stress with
      the persistent adaptive change caused by repeated withdrawals. Stress eliciting
      anxiety-like behavior during abstinence from previous ethanol exposures in rats
      is consistent with stress inducing anxiety during recovery (sobriety) in the
      alcoholic, a circumstance that can facilitate craving and relapse.

PMID- 15726116
TI  - Chronic antidepressant treatment prevents accumulation of gsalpha in cholesterol
      rich, cytoskeletal-associated, plasma membrane domains (lipid rafts).
AB  - Previous studies demonstrated that Gsalpha migrates from a Triton X-100 (TTX-100)
      insoluble membrane domain to a TTX-100 soluble membrane domain in response to
      chronic treatment with the antidepressants desipramine and fluoxetine.
      Antidepressant treatment also causes a Gsalpha redistribution in cells as seen by
      confocal microscopy. The current studies have focused on examining the
      possibility that the association between Gsalpha and the plasma membrane and/or
      cytoskeleton is altered in response to antidepressant treatment, and that this is
      relevant to both Gsalpha redistribution and the increased coupling between
      Gsalpha and adenylyl cyclase seen after chronic antidepressant treatment. Chronic
      treatment of C6 cells with two fuctionally and structurally distinct
      antidepressants, desipramine and fluoxetine, decreased the Gsalpha content of TTX
      100 insoluble membrane domains by as much as 60%, while the inactive fluoxetine
      analog LY368514 had no effect. Disruption of these membrane domains with the
      cholesterol chelator methyl-beta-cyclodextrin altered the localization of many
      proteins involved in the cAMP signaling cascade, but only Gsalpha localization
      was altered by antidepressant treatment. In addition, microtubule disruption with
      colchicine elicited the movement of Gsalpha out of detergent-resistant membrane
      domains in a manner identical to that seen with antidepressant treatment. The
      data presented here further substantiate the role of Gsalpha as a major player in
      antidepressant-induced modification of neuronal signaling and also raise the
      possibility that an interaction between Gsalpha and the cytoskeleton is involved
      in this process.

PMID- 15726118
TI  - Repeated cocaine administration decreases calcineurin (PP2B) but enhances DARPP
      32 modulation of sodium currents in rat nucleus accumbens neurons.
AB  - Our previous studies have demonstrated that repeated cocaine (COC) administration
      reduces voltage-sensitive sodium and calcium currents (I(Na) or VSSCs and I(Ca)
      or VSCCs, respectively) in medium spiny nucleus accumbens (NAc) neurons of rats.
      The present findings further indicate that chronic COC-induced I(Na) reduction in
      NAc neurons is regulated by decreased dephosphorylation and enhanced
      phosphorylation of Na(+) channels. Whole-cell voltage-clamp recordings revealed
      that dephosphorylation of Na(+) channels by calcineurin (CaN) enhanced I(Na),
      while inhibition of protein phosphatase 1 (PP1) by phosphorylated dopamine- and
      cAMP-regulated phosphoprotein (M(r)=32 kDa) (DARPP-32) at the site of threonine
      34 (p-Thr.34-DARPP-32) suppressed I(Na), in freshly dissociated NAc neurons of
      saline-pretreated rats. However, the effects of CaN on enhancing I(Na) were
      significantly attenuated, and the action of p-Thr.34-DARPP-32 to decrease I(Na)
      was mimicked, although not potentiated, by repeated COC pretreatment.
      Dephosphorylation of Na(+) channels by PP1 also enhanced I(Na), but this effect
      of PP1 on I(Na) was not apparently affected by repeated COC administration.
      Western blot analysis indicates that the protein levels of CaN and DARPP-32 were
      significantly decreased and increased, respectively, while the PP1 levels were
      unchanged, in the COC-withdrawn NAc as compared to saline-pretreated controls.
      Combined with previous findings, our results indicate that both CaN and PP1
      modulate the increase in I(Na) via enhancing dephosphorylation, while p-Thr.34
      DARPP-32 reduces I(Na) by inhibiting PP1-induced dephosphorylation, thereby
      stabilizing the phosphorylation state, of Na(+) channels in NAc neurons. They
      also suggest that chronic COC-induced I(Na) reduction may be attributed to a
      reduction in Ca(2+) signaling, which disrupts the physiological balance of
      phosphorylation and dephosphorylation of Na(+) channels.

PMID- 15726117
TI  - Altered expression of 14-3-3 genes in the prefrontal cortex of subjects with
      schizophrenia.
AB  - Seven distinct 14-3-3 proteins are expressed in mammals. One of the 14-3-3 genes
      (eta) has been previously associated with decreased expression in the prefrontal
      cortex (PFC) of subjects with schizophrenia. DNA microarray analysis of the PFC
      of 10 subjects with schizophrenia and 10 matched controls indicated that the
      majority of 14-3-3 genes exhibited moderate to marked decreases in expression in
      schizophrenia, which were significant at the group level across all 10
      comparisons (p<0.021). Selected changes in gene expression were further examined
      using in situ hybridization (ISH) in the same subject pairs as well as in four
      monkeys treated chronically with haloperidol and matched control animals. All
      analyses were performed blind to subject identity and diagnosis, or treatment.
      ISH analysis and multivariate analysis of covariance confirmed the significant
      decreases in expression of two 14-3-3 genes: beta -31.9%, zeta -18.2%. Two other
      14-3-3 genes exhibited more modest decreases in expression levels that were
      significant only in pairwise comparisons that did not factor in post-mortem
      interval or tissue storage time: gamma -11.9%, eta -15.4%. In the PFC of
      haloperidol-treated monkeys, there was no difference in 14-3-3 zeta expression,
      while 14-3-3 beta increased 28% (p<0.05) as a result of neuroleptic treatment.
      Our results suggest that decreased expression of selected 14-3-3 genes is a
      common feature of schizophrenia and that the 14-3-3 beta transcript may be unique
      among the 14-3-3 genes in its increase in response to haloperidol and decrease in
      the disease state.

PMID- 15726119
TI  - The relationship between the systemic inflammatory response and survival in
      patients with transitional cell carcinoma of the urinary bladder.
AB  - The relationship between tumour stage, grade, elevated C-reactive protein
      concentration (<10/>10 mg l(-1)), adjuvant therapy and survival was examined in
      patients with biopsy proven bladder cancer (n=105). On multivariate analysis
      stage (HR 3.37, 95% CI 1.37-8.29, P=0.008), grade (HR 2.01, 95% CI 1.14-3.57,
      P=0.017) and preoperative C-reactive protein (HR 3.31, 95% CI 1.09-10.09,
      P=0.035) were independently associated with cancer-specific survival.

PMID- 15726125
TI  - Congenital portosystemic shunts in dogs and cats.
AB  - Congenital portosystemic shunts (PPS) are abnormal vascular communications that
      allow blood from the intestine to bypass the liver, and are classified as
      intrahepatic or extrahepatic. Clinical signs are generally related to the
      nervous, gastrointestinal or urinary systems, and are often vague. In addition,
      changes present on routine blood analysis are often mild and non-specific. For
      this reason, alternative tests are required for a diagnosis. Diagnostic tests
      include serum bile-acid concentrations, ammonia tolerance test, portography,
      ultrasonography and/or scintigraphy. Medical therapy involves reducing absorption
      of encephalopathic toxins from the gastrointestinal tract and may prolong
      survival. Surgical therapy is aimed at attenuation of the shunting vessel and
      provides improved survival rates. The traditional approach has been complete or
      partial ligation of the shunt. More recent approaches have involved slow,
      progressive attenuation with ameroid constrictors or cellophane banding. Overall,
      prognosis following surgical therapy is good in dogs and fair in cats.

PMID- 15726120
TI  - Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel
      in patients with advanced breast cancer pretreated with anthracyclines: a
      randomised phase III trial of Turkish Oncology Group.
AB  - Our objective was to determine whether oral etoposide and cisplatin combination
      (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC)
      patients pretreated with anthracyclines. From December 1997 to August 2003, 201
      patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in
      each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o.
      twice a day for 7 days and 70 mg m(-2) intravenously (i.v.) on day 1,
      respectively, and it was 175 mg m(-2) on day 1 for paclitaxel. Both treatments
      were repeated every 3 weeks. A median of four cycles of study treatment was given
      in both arms. The response rate obtained in the EoP arm was significantly higher
      (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7
      vs 4 months) (P=0.132). Also, time to progression was significantly in favour of
      the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again
      significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile
      of both groups was similar. Two patients in each arm were lost due to febrile
      neutropenia. The observed activity and acceptable toxicity of EoP endorses the
      employment of this combination in the treatment of ABC following anthracyclines.

PMID- 15726126
TI  - Mycobacterial diseases of deer.
AB  - The most significant mycobacterial diseases of free-living, captive and farmed
      deer are bovine tuberculosis, caused by Mycobacterium bovis, Johne's disease
      (paratuberculosis), caused by Mycobacterium avium subsp paratuberculosis (basonym
      M. paratuberculosis), and avian tuberculosis, caused principally by M. avium
      subsp avium. The first case of M. bovis infection in farmed deer was identified
      in New Zealand in 1978. In 1983, a voluntary scheme was introduced in New Zealand
      to control tuberculosis in farmed deer, followed by a compulsory tuberculosis
      control scheme in 1990. The primary control measure is the slaughter of infected
      animals, detected by skin testing and blood testing, together with movement
      control and vector control. The number of infected deer herds peaked in the mid
      1990s at over 160 herds, but by 30 June 2002 this had been reduced to 79 (1.45%),
      and to 67 (1.23%) by June 2003. Deer-to-deer transmission occurs, but the
      majority of herd breakdowns are believed to be from infected vectors. Factors
      likely to affect the susceptibility of deer include age, environment, population
      density, exposure and genetics. Avian tuberculosis occasionally causes clinical
      disease in wild, captive and farmed deer in New Zealand and overseas.
      Mycobacterium intracellulare, and subspecies of M. avium other than M.
      paratuberculosis, are widespread throughout New Zealand and are thought to be
      largely responsible for the high level of sensitisation to avian purified protein
      derivative (PPD), which is used for comparison purposes in tuberculosis skin
      testing of deer in this country. Infections with these organisms are usually
      subclinical in farmed deer, although M. avium subsp avium commonly causes lesions
      in retropharyngeal, mesenteric and ileocaecal lymph nodes. These lesions cause
      problems because of their gross and microscopic similarity to those due to M.
      bovis infection. Birds and domestic animals are most likely to become infected
      via environmental contamination of food, water, bedding litter or soil, while
      carnivores or scavengers may also become infected by ingesting infected
      carcasses. Johne's disease has been reported in deer in the wild and in zoos,
      especially in North America, the United Kingdom (UK) and Europe. Since first
      being confirmed in farmed deer in New Zealand in 1979, the incidence of Johne's
      disease has increased steadily. To date, M. paratuberculosis has been identified
      in >600 farmed deer on 300 properties. The majority of cases have been identified
      from suspected tuberculous lesions submitted from deer slaughter plants.
      Clinically, Johne's disease in deer is similar to the disease in sheep and
      cattle, with typical signs of loss of weight and condition, and diarrhoea.
      However, outbreaks of Johne's disease frequently occur in young red deer, 8-15
      months of age, whereas the clinical disease in sheep and cattle is sporadic and
      usually affects adults 3-5 years of age. The disease is characterised by a
      chronic granulomatous enteritis and lymphadenitis, especially affecting the
      jejunum and ileum and the mesenteric lymph nodes. Deer affected subclinically may
      have lesions in these lymph nodes at slaughter, which are grossly
      indistinguishable from those due to bovine tuberculosis. Because of the antigenic
      similarity between M. intracellulare and all the subspecies of M. avium,
      including M. paratuberculosis, the diagnostic tests for Johne's disease lack
      sensitivity and specificity, making control difficult.

PMID- 15726121
TI  - Energy balance in patients with advanced NSCLC, metastatic melanoma and
      metastatic breast cancer receiving chemotherapy--a longitudinal study.
AB  - Chemotherapy exerts a variable effect on nutritional status. It is not known
      whether loss of body fat or fat-free mass (FFM) during chemotherapy relates to
      diminished dietary intake, failure to meet elevated energy requirements, or to
      the presence of an acute-phase response. We sought to determine prospective
      measurements of body mass and composition, resting energy expenditure, energy and
      protein intake, and C-reactive protein over a course of chemotherapy in 82
      patients with advanced cancer. There was a large dropout from the study.
      Prospective measurements were obtained in 19 patients with non-small-cell lung
      cancer (NSCLC), 12 with metastatic melanoma and 10 with metastatic breast cancer.
      There were significant increases in energy intake among patients with metastatic
      breast cancer, 873 (266-1480) kJ (mean 95% CI; P<0.01), and metastatic melanoma,
      2513 (523-4503) kJ (P<0.01). Breast cancer patients gained percentage body fat
      over the course of treatment, 2.1 (0.8-3.5%). Gain or loss of body fat correlated
      to mean energy intake throughout chemotherapy in patients with NSCLC (Rs=0.751;
      P<0.01) and metastatic breast cancer (Rs=0.617; P<0.05). The ability to meet or
      exceed energy requirements led to gains in body fat among patients with
      metastatic breast cancer and NSCLC, but did not prevent loss of FFM in these
      groups.

PMID- 15726127
TI  - Pneumonic lesions in lambs in New Zealand: patterns of prevalence and effects on
      production.
AB  - AIM: To describe temporal and spatial patterns of the prevalence of pneumonia in
      lambs in three regions of New Zealand, and determine effects on liveweight gain.
      METHODS: A longitudinal study was conducted in 1999- 2000 on 14 commercial sheep
      farms, five from the Southland region of the South Island, and five from the King
      Country and four from the Northland regions of the North Island. Pneumonia was
      known to be a problem in lambs on all farms selected. On each farm, 400 lambs
      were randomly selected at weaning and allocated at random to one of two groups
      (Groups I and II). Lambs in both groups were weighed at 4-weekly intervals. The
      extent of pneumonic lesions in lungs was scored visually at slaughter in 40
      randomly selected lambs after each weighing (Group I). Lambs in Group II were
      selected for slaughter by the farm manager on a commercial basis of liveweight
      and body condition, then assessed for pneumonic lesions. RESULTS: Prevalence of
      extensive pneumonic lesions (>/=10% lung surface area affected) increased from
      December to March from 1.4 to 10.1% lambs in Southland (n=1,917), 1.2 to 25.7% in
      the King Country (n=1,831), and 4.7 to 21.4% in Northland (n=1,485). Overall,
      42.3% of lambs in both groups had pneumonic lesions (n=5,233) and in 15.1% of
      these, >/=5% of the lung surface area was affected. Daily weight gain in the
      month prior to slaughter was reduced in lambs for which >/=20% lung surface area
      was affected in Group I (p<0.05) but not in Group II. CONCLUSIONS: The
      association between pneumonic lesions and reduced weight gain was highly
      significant in lambs from Group I, but not from Group II. Thus, pneumonia had a
      negative impact on weight gain, and selection by farmers of lambs for slaughter
      counteracted this association in lambs from Group II. CLINICAL RELEVANCE:
      Pneumonia occurs commonly as a subclinical disease in lambs in New Zealand. It
      has no public health significance and is not recorded at slaughter plants nor
      reported to farmer clients. Effects of the disease on daily weight gain of lambs
      is considerable and costly for lamb producers.

PMID- 15726128
TI  - New Zealand veterinarians--demography, remuneration and vacancies.
AB  - AIMS: To determine levels of remuneration for veterinarians in New Zealand, to
      examine associations between putative explanatory factors and gross annual
      remuneration, and to quantify the type and prevalence of vacant positions.
      METHODS: A postal survey to 486 identifiable clinical practices and 53
      identifiable organisations that employ veterinarians was used to gather data for
      the 2-month period of December 2001 to January 2002. RESULTS: Data were produced
      for 972 veterinarians (367 females and 605 males) working in 325 clinical
      practices, and 299 veterinarians (88 females and 211 males) employed by 32
      organisations. Median levels of gross annual remuneration for assistants,
      partners/ shareholders and sole owners working >/=5 days per week in clinical
      practice were NZ$60,000, $90,000 and $75,000, respectively, and for veterinarians
      in organisations, irrespective of number of days per week worked, was $68,000.
      Pay rates increased linearly as the number of years since graduation increased
      for all clinicians and with increasing age for veterinarians in organisations.
      Full-time assistants were likely to be paid more if the practice was rural rather
      than urban in location, if they were males, and if administrative duties were
      part of the job. The same factors, except for sex, were significant for
      remuneration for owners and partners/shareholders working full-time. Their
      remuneration tended to be higher if the practice was involved with either dairy
      or deer work but decreased as the number of animal species serviced increased and
      if they worked >5 days per week. Part-time female veterinarians were generally
      paid more than male counterparts. Male veterinarians working in organisations
      were generally paid about 8% more than their female colleagues. Veterinarians in
      organisations involved with administration at a head office were generally better
      paid than those without administrative duties. Pay rates were, on the whole,
      better in private organisations than in universities, state-owned enterprises,
      government-operated and other types of organisations About 50% of all services
      provided by clinical practices were directed to small animals, 27% to dairy
      cattle and about 10%, 6% and 3% to horses, sheep and beef cattle, and deer,
      respectively. About 31% of veterinarians worked solely with small animals but
      most had multiple species workloads. Of the 325 respondent practices, 98 reported
      vacancies for 119 veterinarians, of which 79 were full-time, 27 part-time and 12
      locum positions. Of the 32 respondent organisations, seven reported vacancies for
      16 mostly full-time positions. Farmer owned co-operative practices were less
      likely than privately owned practices to have full-time vacant positions. The
      only factor identified as influencing part-time vacancies in clinical practices
      was hourly pay rate. Vacancies occurred randomly across practices, irrespective
      of location, and there was no indication of greater demand for services for any
      particular species. The odds of a vacancy in organisations was lower for state
      owned enterprises and private organisations than for government organisations
      (odds ratios (OR)=0.14 and 0.18, respectively). CONCLUSIONS: Relatively more
      females than males worked part-time and 23% of all assistants in clinical
      practice worked part-time. Sex made a significant difference to gross
      remuneration for full-time assistants in clinical practice and for veterinarians
      employed by private or government organisations. In both situations, males were
      generally better paid than females. Female part-time assistants and
      partners/shareholders or sole owners in clinical practice were generally better
      rewarded than their male counterparts. Sex had no effect on remuneration levels
      for owners/ partners working full-time in clinical practices. The study confirmed
      a serious shortage of veterinarians in New Zealand. The probability of a vacancy
      occurring in farmer owned co-operative ('club') practices was lower than in
      private practices. Vacancies were distributed randomly among rural, urban and
      rural/urban practices with no evidence of rural practices being more severely
      affected than urban or rural/urban practices.

PMID- 15726129
TI  - Copper oxide needles administered during early pregnancy improves the copper
      status of ewes and their lambs.
AB  - AIM: To determine the effect of copper oxide (CuO) needles administered orally to
      ewes in early pregnancy on the copper (Cu) status of ewes throughout gestation
      and lactation, and of their lambs from birth to weaning. METHODS: In mid-April,
      after mating, 12 twin-bearing ewes were given an oral capsule containing 5 g CuO
      needles while 12 others served as untreated controls. Changes in Cu status were
      monitored by determining serum and liver Cu concentrations on Days 1, 62, 117,
      153, 185 and 216 in the ewes, and at 1, 36, 68 and 99 days of age for lambs.
      Pasture herbage samples were collected at about 60-day intervals for Cu,
      molybdenum (Mo), iron (Fe) and sulphur (S) determinations. RESULTS: Copper status
      of the ewe flock was adequate, as initial mean serum and liver Cu concentrations
      were 15 micromol/L and 1,060 micromol/kg fresh tissue, respectively. The CuO
      needles did not affect serum Cu concentrations of the ewes or their lambs. Mean
      serum Cu concentration of all lambs at birth was about half that of ewes (8 vs 17
      micromol/L), regardless of Cu supplementation, and not until at least 68 days of
      age was it similar to the dams'. Liver Cu concentrations of lambs at birth were
      also lower than that of the ewes (380 vs 640 micromol/kg fresh tissue among the
      controls), but changed little over time. CuO treatment increased liver Cu
      concentration in ewes for at least 185 days and in lambs for 36 days (p<0.05).
      Among untreated ewes, there was a seasonal decline in mean liver Cu
      concentrations, which were highest in autumn and lowest in early spring (1,060 vs
      370 micromol/kg fresh tissue). The mean pasture mineral concentrations were Cu
      5.7, Mo 0.48, Fe 194 and S 2,900 mg/kg dry matter (DM). CONCLUSIONS: CuO needles
      administered to ewes in early pregnancy increased their Cu status through
      gestation and early lactation, and the Cu status of their lambs for 36 days from
      birth. Serum Cu concentration was not affected by treatment but a marked rise was
      observed in all lambs between birth and 10 weeks of age. CLINICAL RELEVANCE:
      Copper deficiency in young lambs may be conveniently and effectively prevented by
      treating ewes with CuO needles during early pregnancy. The serum Cu concentration
      in lambs <8 weeks old may not reflect the Cu status of the flock.

PMID- 15726130
TI  - Pregnancy status determination in mares using a rapid lateral flow test for
      measuring serum oestrone sulphate.
AB  - AIMS: To develop a means of determining pregnancy status in horses based on
      measuring serum oestrone sulphate (OS) concentrations using a rapid lateral flow
      immunoassay, and to determine the assay's effectiveness using a visual end-point.
      METHODS: Serum samples from mares >100 days post-mating (n=701) were assayed
      using a nitrocellulose membrane-based lateral flow immunoassay device. The device
      was developed using membrane-bound 1,3,5 (10)-estratrien-3-ol-17-one conjugated
      to bovine serum albumin as the capture antigen, and an OS-detection monoclonal
      antibody coupled to colloidal gold as the visible detection reagent.
      Concentrations of the coating antigen and OS monoclonal antibody were optimised
      so that the working range would allow pregnancy status to be determined from a
      visual end-point. The test was run by adding 0.1 ml serum to the sample well of a
      plastic cassette encasing the test membrane. As the serum migrated along the
      membrane, a test dot and control line were generated on it within 5-10 min. The
      intensity of the test dot was inversely proportional to the concentration of OS
      in the serum sample being tested. Results were compared with those from a
      validated OS enzyme immunoassay (EIA) and subsequent foaling or return to oestrus
      of the mares. RESULTS: Serum samples with OS concentrations <10 ng/ml, indicative
      of non-pregnancy in mares >100 days post-mating, generated a test end-point
      consisting of a highly visible test dot and control line, whereas serum OS
      concentrations >50 ng/ml, indicative of pregnancy, generated a control line only.
      The test correctly identified 384/389 (98.7%) non-pregnant mares tested, and
      303/312 (97.1%) pregnant mares tested that were >100 days post-mating. The
      lateral flow test devices were stable for at least 12 months when stored at 4
      degrees C, sealed in aluminium pouches with desiccant. CONCLUSION: This novel,
      rapid, easy-to-use, lateral flow immunoassay offers a practical alternative to
      traditional laboratory- based immunoassays for measuring serum OS concentrations
      in mares for determining their pregnancy status.

PMID- 15726131
TI  - Successful treatment of a pancreatic pseudocyst by omentalisation in a dog.
AB  - CASE HISTORY: A 3-year-old male Labrador retriever was presented with a history
      of dietary indiscretion followed by vomiting and abdominal pain. CLINICAL
      FINDINGS AND TREATMENT: Abdominal ultrasonography revealed the presence of a
      fluid-filled cystic structure in the region of the pancreas. Flocculent, dark
      fluid was drained from the cystic structure during exploratory celiotomy prior to
      resection of the lateral cystic wall. Omentum was sutured into the cystic cavity
      to provide drainage and enhance immune response. A jejunostomy feeding tube was
      placed. Post-surgical care consisted of antibiotic therapy. The dog was
      clinically normal at 1 and 7 months post-operatively and the pancreas appeared
      normal on final ultrasonographic examination. CLINICAL RELEVANCE: This case
      describes the use of omentum to provide physiological drainage of a pancreatic
      pseudocyst. This surgical technique may help clinicians manage patients with this
      condition in the future.

PMID- 15726132
TI  - Resistance to moxidectin and abamectin in naturally acquired Ostertagia
      circumcincta infections in sheep.
AB  - AIM: To investigate the occurrence of resistance to macrocyclic lactone (ML)
      anthelmintics by Ostertagia circumcincta in lambs on a sheep and cattle property
      in the North Island of New Zealand. METHODS: Thirty lambs were randomly allocated
      to one of five equal-sized groups, consisting of an untreated control and four
      treatment groups. The treatments, which were administered at the manufacturer's
      recommended dose rates, included oral moxidectin, oral abamectin (both at 0.2
      mg/kg), an albendazole-levamisole combination, and an albendazole-levamisole
      ivermectin combination. Post mortem worm counts were undertaken 7 days after
      treatment to determine the efficacy of each anthelmintic. RESULTS: The
      albendazole-levamisole and albendazole-levamisole-ivermectin combinations both
      reduced O. circumcincta burdens to zero whereas for moxidectin and abamectin
      efficacies of only 72% and 29%, respectively, were recorded. CONCLUSIONS: These
      results clearly demonstrated the occurrence of resistance to MLs by O.
      circumcincta. Although this is not the first occasion where resistance to this
      anthelmintic family has been detected in this parasite in sheep in New Zealand,
      it is the first instance that resistance to either moxidectin or abamectin has
      been reported.

PMID- 15726133
TI  - A quarter of a century of explorations in organozirconium chemistry.
AB  - Systematic explorations of organozirconium chemistry over the past quarter of a
      century have led to the discoveries and development as well as structural and
      mechanistic clarifications of novel Zr-catalyzed and -promoted carbon-carbon bond
      forming reactions including (i) Ni- or Pd-catalyzed cross-coupling reaction of
      organozirconiums, (ii) Zr-catalyzed carboalumination of alkynes, (iii) Zr
      catalyzed asymmetric carboalumination of alkenes, (iv) generation and
      carbometallative ring expansion of zirconacyclopropanes and zirconacyclopropenes
      and a myriad of their transformations and (v) various organozirconium migratory
      insertion reactions.

PMID- 15726134
TI  - Synthesis and near infrared luminescence of a tetrametallic Zn2Yb2 architecture
      from a trinuclear Zn3L2 Schiff base complex.
AB  - Near infrared luminescence is observed in tetrametallic [Zn2Yb2L2(mu
      OH)2Cl4].2MeCN which is obtained from the Zn3 Schiff-base complex
      [Zn3L2(NO3)2].MeOH, (H2L =N,N'-bis(5-bromo-3-methoxysalicylidene)propylene-1,3
      diamine).

PMID- 15726136
TI  - Dinuclear bis-beta-diketonato ligand derivatives of iron(III) and copper(II) and
      use of the latter as components for the assembly of extended metallo
      supramolecular structures.
AB  - A range of 1,3-aryl linked, bis-beta-diketone derivatives (LH2) has been employed
      to synthesise neutral bis(ligand), dinuclear complexes incorporating square
      planar copper(II) and tris(ligand) dinuclear helical derivatives containing
      octahedral iron(III). The 1H NMR spectra of the free ligands contain singlet
      peaks at ca. 16.2 ppm, indicative of enolic protons, confirming that the (bis)
      enol tautomer is present in solution. An X-ray structure of a ligand from the
      series incorporating tert-butyl terminal substituents confirms that the same
      tautomer persists in the solid and that the relative orientation of the bis-beta
      diketone fragments is such that the coordination vectors lie at approximately 120
      degrees to each other. The planar, dinuclear copper complexes form 1 : 2 adducts
      with pyridine and 4-(dimethylamino)pyridine, confirmed by X-ray structures, that
      incorporate five-coordinate metal centres. Based on this behaviour, the prospect
      of linking copper centres in the dinuclear complexes using the difunctional
      heterocyclic bases, 4,4'-bipyridine, 4,4'-trans-azopyridine and pyrazine as co
      ligands has been probed. However, 4,4'-bipyridine was observed to coordinate
      through only one of its heterocyclic nitrogen atoms in the solid state to form a
      1 : 2 ([Cu2(L)2]: 4,4'-bipyridine) adduct, analogous to the structures obtained
      with the above mono-functional nitrogen bases. Nevertheless, an X-ray structure
      determination shows that the related difunctional base, 4,4'-trans-azopyridine,
      coordinates in a bridging fashion via both its heterocyclic nitrogen atoms on
      alternate sides of each planar [Cu2(L)2] unit to produce an infinite one
      dimensional metallo chain. In contrast, with pyrazine, a new neutral, discrete
      assembly of type [Cu4(L)4(pyrazine)2] is formed. The X-ray structure shows that
      two planar dinuclear complexes are linked by two pyrazine molecules in a sandwich
      arrangement such that the coordination environment of each copper ion is
      approximately square pyramidal with the overall tetranuclear structure thus
      taking the form of a 'dimer of dimers'.

PMID- 15726135
TI  - Detection of secondary structures in 17-mer Ru(II)-labeled single-stranded
      oligonucleotides from luminescence lifetime studies.
AB  - The emission properties of a non intercalating complex, [Ru(TAP)2(dip)]2+ (TAP =
      1,4,5,8-tetraazaphenanthrene; dip = 4,7-diphenyl-1,10-phenanthroline), tethered
      to 17-mer single-stranded oligodeoxyribonucleotides (ODNs) either in the middle
      or at the 5'-end of the sequence, are determined. The results highlight the fact
      that the luminescence of this metallic compound is sufficiently sensitive to its
      microenvironment to probe self-structuration of these short single-stranded ODNs.
      It is shown that the weighted averaged emission lifetimes (tau(M)) along with the
      quenching rate constants of luminescence by oxygen reflect particularly well
      different structures adopted by the different ODNs sequences. The determination
      of these parameters thus offers an elegant way to examine possible structurations
      of synthetic single-stranded ODNs that play important roles in biological
      applications.

PMID- 15726137
TI  - Location of H+ sites in the fast proton-conductor (H3O)SbTeO6 pyrochlore.
AB  - The defect pyrochlore (H3O)SbTeO6 oxide is an excellent proton conductor, showing
      a conductivity value of 10(-1) S cm(-1) at 30 degrees C under saturated water
      vapor partial pressure. It can be prepared by ion exchange from KTeSbO6
      pyrochlore in sulfuric acid at 453 K for 12 h. The full characterization of the
      structure of the (H3O)SbTeO6 pyrochlore, including the location of the H3O+ units
      within the three-dimensional framework, has been carried out by neutron powder
      diffraction. A first Rietveld refinement of the [SbTeO6]- framework was performed
      in the Fd3m space group (a= 10.1510(1) A); a difference Fourier map enabled the
      unambiguous location of the O2 atoms from the H3O+ ions at 32e (x,x,x) positions,
      and subsequently the H atoms at 96g (x,x,z). The (H3O)SbTeO6 crystal structure is
      constituted by a network of randomly distributed Sb(V)O6 and Te(VI)O6 octahedra
      linked by their corners with (Sb,Te)-O1-(Sb,Te) angles of 136.2 degrees.
      Hydronium ions are located off-center around the large 8a cages of the
      pyrochlore. The geometry of the (O2)-H3 units is that of an almost regular
      tetrahedron, with O2 atoms at the center and the three H atoms in three of the
      vertices; the fourth vertex is supposed to be occupied by the O2 lone pair. The
      three O2-H bonds have equal distances of 1.020(8)A. The H3O+ units are linked to
      the O1 framework oxygens by weaker hydrogen bonds, with O1-H bond lengths of
      1.649(7) A. The relatively large thermal factors of O2 and H, of 2.5 and 3.7 A2,
      respectively, suggest that both kinds of atoms are not static at fixed positions
      but could be dynamically fluctuating between crystallographically equivalent
      sites.

PMID- 15726138
TI  - A new palladium nanoparticle catalyst on mesoporous silica prepared from a
      molecular cluster precursor.
AB  - A promising approach to the controlled synthesis of supported nanoparticles
      involves the use of molecular carbonyl clusters as precursors. Molecular metal
      clusters consist of a defined number of structurally ordered atoms, and active
      monodisperse metal particles are formed after dispersing the molecules and
      removing the ligands. An octanuclear palladium cluster precursor with easily
      displaceable ligands was used to generate palladium nanoparticles on mesoporous
      MCM-41. The molecular cluster precursor, [Pd8(CO)8(PMe3)7], was directly adsorbed
      from solution onto MCM-41, followed by gentle thermolysis which yielded small
      metal nanoparticles. Compared to MCM-41-based catalysts prepared from palladium
      salts by conventional methods, this cluster-derived palladium catalyst has shown
      an efficient activity for liquid-phase hydrogenation of alkenes.

PMID- 15726139
TI  - Luminescent digold ethynyl thienothiophene and dithienothiophene complexes; their
      synthesis and structural characterisation.
AB  - A series of protected and terminal dialkynes with extended pi-conjugation through
      the fused oligothienyl linker unit in the backbone, 2,5
      bis(trimethylsilylethynyl)thieno[3,2-b]thiophene 1a, 5,5'
      bis(trimethylsilylethynyl)dithieno[3,2-b:2',3'-d]thiophene 1b, 2,5
      bis(ethynyl)thieno[3,2-b]thiophene 2a, 5,5'-bis(ethynyl)dithieno[3,2-b:2',3'
      d]thiophene 2b, has been synthesized and characterised. The digold alkynyl
      complexes [(Ph3P)Au(C[triple bond]C)(C6H2S2)(C[triple bond]C)Au(PPh3)] 3a and
      [(Ph3P)Au(C[triple bond]C)(C8H2S3)(C[triple bond]C)Au(PPh3)] 3b have then been
      prepared by the reaction of two equivalents of Ph3PAuCl and a methanolic KOH
      solution of 1a and 1b, respectively. The complexes have been characterised
      spectroscopically. The crystal structures show that the gold centres adopt a
      linear two-coordinate geometry appropriate for Au(i) complexes. Within the
      crystals adjacent molecules are linked by Au...S intermolecular interactions in
      the range 3.48-3.89 A, but there are no short Au...Au contacts. The absence of
      Au...Au interactions in solution is confirmed by UV/visible absorption and
      emission spectroscopy, the spectra being dominated by ligand-centred pi-pi*
      interactions.

PMID- 15726140
TI  - New [Mo(eta3-allyl)(CO)2L3]+ complexes with monodentate or tridentate nitrogen
      donor ligands.
AB  - Cationic complexes [Mo(eta(3)-allyl)(CO)2L3]+ (L3 = either nitrogen-donor
      tridentate ligand or three monodentate ligands) were prepared in high yield and
      under mild conditions using as precursors either the triflato complex [Mo(eta(3)
      allyl)(OTf)(CO)2(NCMe)2] or the combination of the chloro complex [Mo(eta(3)
      allyl)Cl(CO)2(NCMe)2] and the salt NaBAr'(4)(Ar'= 3,5
      bis(trifluoromethyl)phenyl). The tridentate ligands employed were 2,2':6',2'
      terpyridine (terpy) and cis,cis-1,3,5-cyclohexanetriamine (CHTA), whereas the
      monodentate ligands imidazole (im) and 3,5-dimethylpyrazole (dmpz) were chosen.
      In order to stabilize the labile intermediates, an excess of acetonitrile was
      used in most of the syntheses. However, the pyrazole complex was prepared through
      a nitrile-free route to avoid reactions at the coordinated nitrile. The solid
      state structures of [Mo(eta(3)-methallyl)(CO)2(terpy)]OTf (2), [Mo(eta(3)
      methallyl)(CO)2(CHTA)]BAr'4 (3), [Mo(eta(3)-methallyl)(CO)2(NCMe)3]BAr'4 (4),
      [Mo(eta(3)-allyl)(CO)2(im)3]OTf (5) and [Mo(eta(3)-allyl)(CO)2(dmpz)3]BAr'4 (6)
      were determined by means of single-crystal X-ray diffraction.

PMID- 15726141
TI  - Probing the nature of the Co(III) ion in cobalamins: a comparison of the reaction
      of aquacobalamin (vitamin B12a) and aqua-10-chlorocobalamin with some anionic and
      N-donor ligands.
AB  - To probe the cis effect of the corrin macrocycle in vitamin B12 derivatives,
      equilibrium constants for the substitution of coordinated H2O in aquacobalamin
      (vitamin B12a, H2OCbl+) and in aqua-10-chlorocobalamin, H2O-10-ClCbl+, (in which
      Cl has replaced the C10 H) by an exogenous ligand, L (L = an anion, NO2-, SCN-,
      N3-, OCN-, S2O3(2-), NCSe- or a neutral N-donor, CH3NH2, pyridine, imidazole)
      have been determined. The cis influence reported in the electronic spectra of the
      cobalamins is observed in the spectra of L-10-ClCbls as well. Anionic ligands
      bind more strongly to H2O-10-ClCbl+ than to H2OCbl+ with log K values between
      0.10 and 0.63 (average 0.26) larger; the converse is true for the neutral N-donor
      ligands, where log K is between 0.17 and 0.3 (average 0.25) smaller. Semi
      empirical molecular orbital (SEMO) calculations using the ZINDO/1 model on the
      hydroxo complexes show that charge density is delocalised from the axial donor
      atom to the metal and Cl. This explains why coordinated OH- is a poorer base in
      HO-10-ClCbl than in HOCbl and the pK(a) of H2O-10-ClCbl+ is lower than that of
      H2OCbl+. It further explains why, because of the ability of the metal in concert
      with the C10 Cl to accept charge density from the ligand, an anionic ligand will
      bind more strongly to Co(III) in H2O-10-ClCbl+ than in H2OCbl+. The kinetics of
      the replacement of coordinated H2O by two probe ligand, pyridine and azide, were
      determined. The rate constants for substitution of H2O in H2O-10-ClCbl+ by
      pyridine show saturation, whilst those for substitution by N3- do not; this is
      inconsistent with a purely dissociative mechanism and the reactions proceed
      through an interchange mechanism. The values of the activation parameters are
      more positive for the reaction between these ligands and H2OCbl+, than for their
      reaction with H2O-10-ClCbl+. This is interpreted to mean that the transition
      state in the reaction of H2O-10-ClCbl+ occurs earlier along the reaction
      coordinate. In the temperature range studied, H2O-10-ClCbl+ reacts more slowly
      with py and N3- than does H2OCbl+. SEMO calculations indicate that as the Co-O
      bond to the departing H(2)O molecule is stretched, the charge density on Co in
      H2OCbl+ is always lower than on Co in H2O-10-ClCbl+. This suggests that the
      former is a better electrophile towards the incoming ligand, and offers an
      explanation for the kinetics observations.

PMID- 15726142
TI  - Metal-assisted red light-induced DNA cleavage by ternary L-methionine copper(II)
      complexes of planar heterocyclic bases.
AB  - Ternary copper(II) complexes [Cu(l-met)B(Solv)](ClO4) (1-4), where B is a N,N
      donor heterocyclic base like 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen,
      2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2'],3'
      c]phenazene (dppz, 4), are prepared and their DNA binding and photo-induced DNA
      cleavage activity studied (L-Hmet =L-methionine). Complex 2, structurally
      characterized by X-ray crystallography, shows a square pyramidal (4 + 1)
      coordination geometry in which the N,O-donor L-methionine and N,N-donor
      heterocyclic base bind at the basal plane and a solvent molecule is coordinated
      at the axial site. The complexes display a d-d band at approximately 600 nm in
      DMF and exhibit a cyclic voltammetric response due to the Cu(II)/Cu(I) couple
      near -0.1 V in DMF-Tris-HCl buffer. The complexes display significant binding
      propensity to the calf thymus DNA in the order: 4(dppz) > 3(dpq) > 2(phen>>
      1(bpy). Control cleavage experiments using pUC19 supercoiled DNA and distamycin
      suggest major groove binding for the dppz and minor groove binding for the other
      complexes. Complexes 2-4 show efficient DNA cleavage activity on UV (365 nm) or
      red light (632.8 nm) irradiation via a mechanistic pathway involving formation of
      singlet oxygen as the reactive species. The DNA cleavage activity of the dpq
      complex is found to be significantly more than its dppz and phen analogues.

PMID- 15726143
TI  - The first carborane triflates: synthesis and reactivity of 1
      trifluoromethanesulfonylmethyl- and 1,2-bis(trifluoromethanesulfonylmethyl)-o
      carborane.
AB  - The first carborane triflates, namely, 1-trifluoromethanesulfonylmethyl-o
      carborane (2) and 1,2-bis(trifluoromethanesulfonylmethyl)-o-carborane (7), were
      obtained in high yields in the reactions of 1-hydroxymethyl-o-carborane (1) or
      1,2-bis(hydroxymethyl)-o-carborane (6) with triflic anhydride (Tf2O) in CH2Cl2 in
      the presence of pyridine. When an excess of pyridine is employed, 1-o
      carboranylmethylpyridinium triflate (3), which retains a closo-icosahedral
      structure, or a pyridinium salt (4) with a zwitterionic nido-dicarbaundecaborate
      anion are obtained from 1, while the nido compound 8 is formed from 6. The
      reaction of compound 2 or 7 with excess pyridine also gave 3 or 8, respectively.
      Compound 2 proved to be a convenient carboranylmethylating agent which reacts
      with nucleophiles (e.g., potassium phthalimide, PPh3 or KCN) to give the
      corresponding substitution products N-[(o-carboranyl-1-yl)methyl]phthalimide (9),
      o-carboranylmethylphosphonium salt 10, and 1-cyanomethyl-o-carborane (11). All
      compounds were characterized by 1H and 11B NMR spectroscopy. The structures of
      compounds 4, 7 and 8 were established by X-ray analysis.

PMID- 15726144
TI  - Diphosphacarborane analogues of ferrocene: the synthesis of two isomeric twelve
      vertex closo-[(eta5-C5H5)FeP2CB8H9] complexes.
AB  - The reaction of the Tl+ salt of the [nido-7,8,9-P2CB8H9]- anion (1-) with
      [CpFe(CO)2I](Cp =eta(5)-C5H5) in refluxing mesitylene for 12 h gives mixed
      sandwich [1-Cp-closo-1,2,3,4-FeP2CB8H9] (2) (yield 63%). Reaction of the PPh4+
      salt of the isomeric [nido-7,8,10-P2CB8H9]- anion 3- with [CpFe(CO)2I] in
      refluxing mesitylene gives [1-Cp-closo-1,2,3,5-FeP2CB8H9]4 (yield 56%), isomeric
      with 2. Compound 4 also results (yield 92%) from the sublimation of 2 under argon
      at ca. 350 degrees C. The constitution of all compounds is established by mass
      spectrometry, IR spectroscopy and multinuclear NMR spectroscopy (1H, 11B, 31P,
      and 13C; two-dimensional [11B-11B]-COSY, and 1H- 11B(selective)), further
      confirmed in the case of 4 by a single-crystal X-ray diffraction analysis.

PMID- 15726145
TI  - Bis(arylimino)pyridine derivatives of Group 4 metals: preparation,
      characterization and activity in ethylene polymerization.
AB  - Titanium tetrachloride reacts with 2,6-bis[(1-phenylimino)ethyl]pyridine, 1, and
      2,6-bis[1-(2,6-diisopropylphenylimino)ethyl]pyridine, 2, giving the adducts of
      general formulae [Ti1Cl3]Cl, 3, and [Ti2Cl3]Cl, 6, the latter through the
      intermediacy of the covalently bonded [Ti2Cl4], 4. Heating 6 leads to reduction
      to the titanium(III) derivative [Ti2Cl3], 12, the latter characterized by X-ray
      diffraction methods. The reaction of [Ti1Cl3]Cl with a toluene solution of MAO
      proceeds with methylation at the ortho-position of the pyridine ring to give the
      titanium(iv) derivative [Ti(C22H21N3)Cl3], 8. The reaction of [Ti2Cl3]Cl with MAO
      gives a mixture of products containing [Ti2Cl2(OAlCl3)], 9. Compound 9, which has
      been prepared independently by reacting 6 with AlOCl, is a rare case of a
      compound containing the -OAlCl3 moiety, as shown by a single-crystal X-ray
      diffraction study. From the tetrachlorides of zirconium and hafnium with 1 or 2,
      the corresponding adducts [M(L)Cl4] have been obtained in high yields. These
      derivatives of Group 4 metals act as ethylene polymerization catalytic
      precursors: the substitution of the phenyl ring of the imino fragment strongly
      influences the catalytic activity which is 5,544 kg(PE) mol(Ti)(-1) h(-1) in the
      case of 3 and 267 kg(PE) mol(Ti)(-1) h(-1) with 6. Catalytic activity has been
      observed for zirconium and hafnium too, the activity decreasing from zirconium to
      hafnium, under comparable conditions.

PMID- 15726146
TI  - Dinuclear complexes of a pseudocalixarene macrocycle: structural consequences of
      intramolecular hydrogen bonding.
AB  - A series of dinuclear complexes of a pseudocalixarene macrocycle H6L containing
      two 2,2'-methylenediphenol groups have been synthesised and structurally
      characterised. Using divalent metal ions, complexes containing a common
      hyperbolic paraboloid (saddle) M2(H4L)2+ core are formed. The structure is
      controlled by two strong O-H-O interactions resulting from metal ion-promoted
      monodeprotonation of the methylenediphenol units. The metal ions are located in a
      cleft within which neutral or anionic guests can bind. Use of trivalent metal
      ions leads to complete deprotonation of the phenol groups and loss of the saddle
      conformation.

PMID- 15726147
TI  - Regioselective nucleophilic addition of triphenylphosphine to the
      nitrosylruthenium alkynyl complexes having a hydrotris(pyrazol-1-yl)borate:
      formation of phosphonio-alkenyl, alkynyl, and allenyl species.
AB  - A nitrosylruthenium alkynyl complex of TpRuCl(C[triple bond]CPh)(NO)(1a) was
      reacted with PPh3 in the presence of HBF4.Et2O at room temperature to give a beta
      phosphonio-alkenyl complex (E)-[TpRuCl{CH=C(PPh3)Ph}(NO)]BF4(2.BF4). On the other
      hand, for gamma-hydroxyalkynyl complexes TpRuCl{C[triple bond]CC(R)2OH}(NO)(R =
      Me (1b), Ph (1c), H (1d)), similar treatments with PPh3 were found to give gamma
      phosphonio-alkynyl [TpRuCl{C[triple bond]CC(Me)2PPh3}(NO)]BF4(3.BF4),alpha
      phosphonio-allenyl [TpRuCl{C(PPh3)=C=CPh2}(NO)]BF4(4.BF4), and a novel product of
      gamma-hydroxy-beta-phosphonio-alkenyl (E)
      [TpRuCl{CH=C(PPh3)CH2OH}(NO)]BF4(5.BF4), respectively. Dominant factors for the
      selectivity in affording 3-5 were associated with the steric congestion and
      electronic properties at the gamma-carbons, along with those around the metal
      fragment. From the bis(alkynyl) complex TpRu(C[triple bond]CPh)2(NO)6, a bis(beta
      phosphonio-alkenyl)(E,E)-[TpRu{CH=C(PPh3)Ph}2(NO)](BF4)2{7.(BF4)2} was produced
      at room temperature. However, similar reactions at 0 degrees C gave an alkynyl
      beta-phosphonio-alkenyl complex (E)-[TpRu(C[triple
      bondCPh){CH=C(PPh3)Ph}(NO)]BF4(8.BF4) as a sole product, of which additional
      hydration in the presence of HBF4.Et2O afforded a [small beta]-phosphonio-alkenyl
      ketonyl (E)-[TpRu{CH2C(O)Ph}{CH=C(PPh3)Ph}(NO)]BF(.9BF4). Five complexes, 2-5 and
      7 were crystallographically characterized.

PMID- 15726148
TI  - A pyrimidine thiolate Rh(I) complex: structure, bonding and one-dimensional
      interactions in solid and in solution.
AB  - The reaction of [Rh(micro-Cl)(COD)]2 with 4,6-dimethyl-pyrimidinethiolate (Me2
      pymt) and subsequent substitution of COD by CO yields [Rh(Me2-pymt)(CO)2]. The
      stacking pattern found in this compound is in contradiction with previously
      studied comparable square-planar complexes of type d8-[M(chelate)(monodentate)2]
      in which each ligand has different pi-acidic character. A theoretical study of
      the intermolecular interactions and conformation of the title compound has been
      carried out, combining semi-empirical band calculations on the real chains and ab
      initio(MP2 level) calculations on a model dimer. The combination of electronic
      and steric effects determines the rotation of the successive monomers and the
      deviation from linearity of the one-dimensional stacks. Its behaviour in solution
      is also special, developing a blue colour and forming micelles, when adding water
      to acetone solutions.

PMID- 15726149
TI  - Synthesis of iron(II), manganese(II) cobalt(II) and ruthenium(II) complexes
      containing tridentate nitrogen ligands and their application in the catalytic
      oxidation of alkanes.
AB  - A series of Fe(II), Mn(II), Co(II) and Ru(II) complexes containing
      bis(imino)pyridine or bis(amino)pyridine ligands and weakly coordinating triflate
      (OTf-) or non-coordinating SbF6- anions have been prepared. The complexes have
      been fully characterized including several solid-state structure analyses. Two
      unusual mono-chelate six-coordinate bis(imino)pyridine Fe(II) and Mn(II)
      complexes have been observed. The catalytic properties of the complexes for the
      oxidation of cyclohexane with H2O2 have been evaluated. Only the Fe(II) complexes
      have shown catalytic activity, which is mainly due to Fenton-type free radical
      auto-oxidation.

PMID- 15726151
TI  - Ligand rotation in [Ar(R)N]3M-N2-M'[N(R)Ar]3(M, M' = MoIII, NbIII; R = iPr and
      tBu) dimers.
AB  - Earlier calculations on the model N2-bridged dimer (micro-N2)-{Mo[NH2]3}2
      revealed that ligand rotation away from a trigonal arrangement around the metal
      centres was energetically favourable resulting in a reversal of the singlet and
      triplet energies such that the singlet state was stabilized 13 kJ mol(-1) below
      the D(3d) triplet structure. These calculations, however, ignored the steric bulk
      of the amide ligands N(R)Ar (R =iPr and tBu, Ar = 3,5-C6H3Me2) which may prevent
      or limit the extent of ligand rotation. In order to investigate the consequences
      of steric crowding, density functional calculations using QM/MM techniques have
      been performed on the Mo(III)Mo(III) and Mo(III)Nb(III) intermediate dimer
      complexes (mu-N(2))-{Mo[N(R)Ar]3}2 and [Ar(R)N]3Mo-(mu-N2)-Nb[N(R)Ar]3 formed
      when three-coordinate Mo[N(R)Ar]3 and Nb[N(R)Ar]3 react with dinitrogen. The
      calculations indicate that ligand rotation away from a trigonal arrangement is
      energetically favourable for all of the ligands investigated and that the
      distortion is largely electronic in origin. However, the steric constraints of
      the bulky amide groups do play a role in determining the final orientation of the
      ligands, in particular, whether the ligands are rotated at one or both metal
      centres of the dimer. Analogous to the model system, QM/MM calculations predict a
      singlet ground state for the (mu-N2)-{Mo[N(R)Ar]3}2 dimers, a result which is
      seemingly at odds with the experimental triplet ground state found for the
      related (mu-N2)-{Mo[N(tBu)Ph]3}2 system. However, QM/MM calculations on the (mu
      N2)-{Mo[N(tBu)Ph]3}2 dimer reveal that the singlet-triplet gap is nearly 20 kJ
      mol(-1) smaller and therefore this complex is expected to exhibit very different
      magnetic behaviour to the (mu-N2)-{Mo[N(R)Ar]3}2 system.

PMID- 15726150
TI  - Novel platinum(II) ammine hydroxamate and hydroximate complexes and the platinum
      assisted hydrolysis of hydroxamic acids.
AB  - The 2-pyridinecarboxylate (2-pyca) platinum(IV) complex [2-pycaH2][PtCl4(2
      pyca)].H2O, 1, has been synthesised from K2[PtCl4] following the hydrolysis of 2
      pyridinehydroxamic acid (2-pyhaH) in the presence of H2O2, and directly from
      K2[PtCl6] and picolinic acid. Structural characterisation of 1 reveals octahedral
      geometry about platinum(IV) consisting of a (N,O)-bidentate pyridinecarboxylate
      ligand and four chloride ligands. A mechanism for the hydrolysis of 2
      pyridinehydroxamic acid to 2-pyridinecarboxylic acid is proposed. Two novel
      coordination modes of hydroxamic acids to platinum(II) are also reported. The
      dinuclear platinum ammine hydroximato complex, [{cis-Pt(NH3)2}2(mu-2-pyhaH(
      1))](ClO4)2.H2O, 3, has been synthesised where the two platinum(II) centres are
      bridged via(O,O) and (N,N) coordination. The latter coordination mode is via the
      hydroximate nitrogen and the pyridine nitrogen. The corresponding mononuclear
      platinum(II) pyridinehydroxamate complex, [cis-Pt(NH3)2(2-pyha)]ClO4, 4, has been
      synthesised. Spectroscopic studies indicate that the coordination mode is through
      the pyridine nitrogen and hydroxamate oxygen atoms (N,O).

PMID- 15726152
TI  - Structural measures of element-oxygen bond covalency from the changes to the
      delocalisation of the carboxylate ligand.
AB  - The data set of more than 40,000 crystal structures containing the carboxylate
      group that have been deposited in the CSD has been used to examine the structural
      changes that occur in the carboxylate C-O bond lengths upon binding to different
      elemental centres. We report here quantifiable structural changes that are
      dependent on the elemental centre with which the group is interacting. For the
      main-group elements the trends are entirely periodic and follow those
      traditionally associated with covalency; elements exhibiting electronegativity
      closest to that of oxygen exhibit the largest structural change. In addition, we
      find the measure is extendable to both the transition metals and the lanthanoids
      and actinoids. Amongst the transition metals the trends of Pauling neutrality are
      not only maintained, but are quantifiable. The difference between the two C-O
      bond lengths increases with oxidation state and decreases with an increase in
      coordination number. All of the lanthanoids exhibit covalency within error of
      each other and the bonds to the actinoids are found to be more covalent than
      those to the lanthanoids. From the data analysis we are able to derive a
      correlation between the lengths of the two carboxylate arms that allows us to
      quantify percentage covalent character defined in terms of the resonance
      contributions to the carboxylate group.

PMID- 15726153
TI  - IrII(ethene): metal or carbon radical? Part II: oxygenation via iridium or direct
      oxygenation at ethene?
AB  - Treatment of [(Me3tpa)IrII(ethene)]2+ (Me(3)tpa =N,N,N-tri(6-methyl-2
      pyridylmethyl)amine)(1(2+)) with dioxygen in weakly coordinating solvents results
      in formation of [(Me3tpa)IrIII(ethene)(superoxo)]2+ (4a2+). In the presence of
      DMPO (DMPO = 5,5-dimethyl-2-pyrrolidine-1-oxide) DMPO is substituted for ethene,
      and subsequently oxidized to DMPOX by the superoxo fragment to give
      [(Me3tpa)IrIII(DMPOX)]2+ (7(2+); DMPOX = 5,5-dimethyl-2-pyrrolidone-1-oxide). In
      acetonitrile, in the absence of DMPO, oxygenation of 1(2+) to
      [(Me3tpa)IrIII(formylmethyl)(MeCN)]2+ (2(2+)) is observed. In the presence of
      DMPO the formation of 2(2+) and 7(2+) is competing. Oxygenation of 1(2+) to 2(2+)
      may proceed via 4a(2+), involving an insertion mechanism at the metal. However, a
      mechanism based on olefin ligand non-innocence seems a reasonable alternative.
      This involves formation of acetonitrile adduct [(Me3tpa)Ir(ethene)(MeCN)]2+
      (3(2+)), which has a significant metalla-ethyl radical (IrIII-CH2CH2*) character,
      allowing attack of 3O2 directly at the ethene ligand. Both pathways are discussed
      on the basis of experimental observations and DFT geometry optimizations.

PMID- 15726154
TI  - Linear and cyclic tetranuclear copper(I) complexes containing anions of N,N'
      bis(pyrimidine-2-yl)formamidine.
AB  - The reaction of Kpmf (pmf = anion of N,N[prime or minute]-bis(pyrimidyl-2
      yl)formamidine, Hpmf) with CuSCN afforded the complexes K[Cu4(pmF)3(SCN)2], 1,
      and Cu(4)(pmf)4, 2. Reaction of 1 with [(n-Bu)4N]PF6 in THF gave the complex [(n
      Bu)4N][Cu4(pmf)3(SCN)2], 3. Their structures were characterized by X-ray
      crystallography. Complexes 1 and 3 are the first linear tetranuclear complexes
      containing only Cu(I) atoms, while complex 2 is cyclic. The four Cu(I) atoms of
      complexes 1 and 3 are helically bridged by three tetradentate pmf- ligands. The
      [Cu4(pmf)3(SCN)2]- anions of 1 show weak interactions with adjacent [K(THF)5]+
      cations through the sulfur atoms, forming infinite chains which are subjected to
      a series of intermolecular pi-pi interactions. In complex 2, the pmf- ligands are
      coordinated to the copper atoms in bidentate fashion through the two central
      amine nitrogen atoms, leaving the pyrimidine nitrogen atoms uncoordinated.
      Unexpected fluxional behaviors were observed for complexes 1 and 3 in solution.
      By the DNMR analysis, the free energy of activation (DeltaGc(not equal)) for the
      exchange is 12.8 kcal mol(-1) at 278 K (T(c)), and the rate constant of exchange
      (K(c)) is 470 s(-1) for 1. The DeltaGc(not equal) and Kc are 12.6 kcal mol(-1) at
      273 K and 433 s(-1), respectively, for 3.

PMID- 15726155
TI  - Polystyrene-supported dicyclohexylphenylphosphine adducts of amine- and phosphite
      based palladacycles in the Suzuki coupling of aryl chlorides.
AB  - The polystyrene-immobilised palladacyclic complexes [Pd(TFA)(kappa2-N,C
      C6H4CH2NMe2){P(C6H4-4-PS)Cy2}] and [PdCl(kappa2-P,C-{P(OC6H2-2,4-tBu2)(OC6H3-2,4
      tBu2)2}{P(C6H4-4-PS)Cy2}](PS = polystyrene) and the homogeneous analogues
      [Pd(TFA)(kappa2-N,C-C6H4CH2NMe2)(PPhCy2)] and PdCl(kappa2-P,C-{P(OC6H2-2,4
      tBu2)(OC6H3-2,4-tBu2)2}(PPhCy2)] were synthesised and characterised. The X-ray
      structure of one of the homogeneous analogues, [Pd(TFA)(kappa2-N,C
      C6H4CH2NMe2)(PPhCy2)] was determined. All the complexes have been tested and show
      good activity in the Suzuki coupling of aryl chloride substrates. While the
      polystyrene-immobilised complexes are not recyclable, they are easily extracted
      and show low levels of palladium leaching.

PMID- 15726156
TI  - Synthesis, structures and reactions of lithium complexes of [(o
      RCHC6H4)PPh2=NSiMe3]-(R = H, SiMe3) ligands.
AB  - N-Trimethylsilyl o-methylphenyldiphenylphosphinimine, (o-MeC6H4)PPh2=NSiMe3 (1),
      was prepared by reaction of Ph2P(Br)=NSiMe3 with o-methylphenyllithium. Treatment
      of 1 with LiBun and then Me3SiCl afforded (o-Me3SiCH2C6H4)PPh2=NSiMe3 (2).
      Lithiations of both 1 and 2 with LiBu(n) in the presence of tmen gave crystalline
      lithium complexes [Li{CH(R)C6H4(PPh(2=NSiMe3)-.tmen](3, R = H; 4, R = SiMe3).
      From the mother liquor of 4, traces of the tmen-bridged complex
      [Li{CH(SiMe3)C6H4(PPh2=NSiMe3)-2}]2(mu-tmen) (5) were obtained. Reaction of 2
      with LiBun in Et2O yielded complex [Li{CH(SiMe3)C6H4(PPh2=NSiMe3)-2}.OEt2] (6).
      Reaction of lithiated with Me2SiCl2 in a 2:1 molar ratio afforded dimethylsilyl
      bridged compound Me2Si[CH2C6H4(PPh2=NSiMe3)-2]2 (7). Lithiation of 7 with two
      equivalents of LiBun in Et2O yielded [Li2{(CHC6H4(PPh2=NSiMe3)
      2)2SiMe2}.0.5OEt2](8.0.5OEt2). Treatment of 4 with PhCN formed a lithium enamide
      complex [Li{N(SiMe3)C(Ph)CHC6H4(PPh2=NSiMe3)-2}.tmen] (9). Reaction of two
      equivalents of 5 with 1,4-dicyanobenzene gave a dilithium complex
      [{Li(OEt2)2}2(1,4-{C(N(SiMe3)CHC6H4(PPh2=NSiMe3)-2}2C6H4)] (10). All compounds
      were characterised by NMR spectroscopy and elemental analyses. The structures of
      compounds 2, 3, 5, 6 and 9 have been determined by single crystal X-ray
      diffraction techniques.

PMID- 15726157
TI  - Non-covalent side-chain polymers: design principles, functionalization
      strategies, and perspectives.
AB  - Side-chain functionalized polymers have a profound impact on complex materials
      synthesis with a variety of applications ranging from liquid crystalline and
      electro-optical materials to drug delivery systems. In the last decade, the use
      of self-assembly towards the synthesis of side-chain functionalized polymers has
      been investigated extensively as a result of its modular character and ease of
      synthesis. This tutorial review describes recent advances in the literature and
      establishes basic design principles and synthetic approaches towards the
      fabrication of supramolecular materials that are based on side-chain
      functionalized polymers.

PMID- 15726158
TI  - Highly stable olefin-Cu(I) coordination oligomers and polymers.
AB  - Highly stable Cu(I)-olefin coordination oligomers and polymers have been
      successfully prepared and applied to construct metal-organic frameworks (MOFs)
      with interesting physical and chemical functions in recent years. In this review,
      we present the olefin-Cu(I) coordination oligomers and polymers and their novel
      physical properties. From structure to functions, particular emphasis is placed
      on the coordination and organometallic chemistry of olefin-Cu(I) coordination
      oligomers and polymers, their structures and potential applications as solids
      possessing unusual physical functional properties such as electrochemical, chiral
      separation, fluorescent sensing and ferroelectricity.

PMID- 15726159
TI  - Hierarchical self-assembly of columnar aggregates.
AB  - Biology often uses hierarchical self-assembly to produce complex functional
      structures from smaller components. At each level of this stepwise process, non
      covalent interactions bring together the subunits of a lower level of complexity,
      using the information encoded in their structures. Applying this approach to
      synthetic systems represents a formidable challenge, because it requires a high
      degree of command of non-covalent interactions. In this tutorial review, recent
      developments in the hierarchical self-assembly of discrete columnar aggregates
      are discussed.

PMID- 15726160
TI  - The application of micro reactors for organic synthesis.
AB  - This tutorial review describes how micro reactors are being applied to synthetic
      chemistry covering a wide range of applications, from the preparation of
      nanograms of material for drug discovery and screening to the multi-tonne
      production of fine chemicals. This article explores how miniaturisation may
      revolutionise chemical synthesis and demonstrates that products are generated in
      higher yield and purity compared to the equivalent bulk reactions, in much
      shorter periods of time.

PMID- 15726161
TI  - Computer-aided organic synthesis.
AB  - It is tempting for those in the field of organic synthesis to liken the process
      of retrosynthesis to a game of chess. That the world chess champion was recently
      defeated by a computer leads us to think that perhaps new and powerful computing
      methods could be applied to synthetic problems. Here the analogy between
      synthesis and chess is outlined. Achievements in the 35-year history of computer
      aided synthetic design are described, followed by some more recent developments.

PMID- 15726162
TI  - Post-polymerization functionalization of polyolefins.
AB  - Polyolefins are macromolecular alkanes and include the most familiar and most
      commercially produced plastic, polyethylene. The low cost of these materials
      combined with their diverse and desirable property profiles drive such large
      scale production. One property that renders polyolefins so attractive is their
      resistance to harsh chemical environments. However, this attribute becomes a
      severe limitation when attempting to chemically convert these plastics into value
      added materials. Functionalization of polymers is a useful methodology for the
      generation of new materials with wide ranging applications, and this tutorial
      review describes both new and established methods for the post-polymerization
      modification of polyolefins.

PMID- 15726163
TI  - Stimuli responsive polymers for biomedical applications.
AB  - Polymers that can respond to external stimuli are of great interest in medicine,
      especially as controlled drug release vehicles. In this critical review, we
      consider the types of stimulus response used in therapeutic applications and the
      main classes of responsive materials developed to date. Particular emphasis is
      placed on the wide-ranging possibilities for the biomedical use of these
      polymers, ranging from drug delivery systems and cell adhesion mediators to
      controllers of enzyme function and gene expression (134 references).

PMID- 15726164
TI  - On the role(s) of additives in bioinspired silicification.
AB  - Biological organisms are able to direct the formation of patterned and
      hierarchical biomineral structures. Extractable organic materials have been found
      entrapped in diatom, sponge and plant biosilica, some of which have been isolated
      by selective chemical dissolution methods and their composition and structure
      studied. Information gained from the bioextracts has inspired materials chemists
      to design biomimetic analogues and develop bioinspired synthetic schemes for
      silica formation. The results obtained from bioinspired silicification
      investigations are hypothesised to arise from specific modes of action of the
      organic additives, which are described in this review. Specifically, additives in
      bioinspired silicification act either as catalysts, aggregation promoting agents
      or structure-directing agents or more typically, exhibit a combination of these
      behaviours.

PMID- 15726165
TI  - Metallodithiolato ligands as bridges in multiply bonded dimolybdenum complexes.
AB  - For the first time, a NiN2S2 metallothiolate ligand is used as a bidentate
      bridging ligand for a multiply bonded dimetal unit.

PMID- 15726166
TI  - A family of heterometallic wheels containing potentially fourteen hundred
      siblings.
AB  - The synthesis and structure of new heterometallic wheels are reported, with
      preliminary studies of selected compounds.

PMID- 15726168
TI  - Stoichiometrically-controlled reactivity and supramolecular storage of
      butylmagnesiate anions.
AB  - Toluene is metallated by DABCO-activated disodium tetrabutylmagnesiate, but not
      by DABCO-activated monosodium tributylmagnesiate; this distinction is
      rationalised by DFT calculations on model systems, and the crystal structure of
      the main non-metallated product, which shows interstitial MgBu4(2-) dianions
      within a polycationic network, is reported.

PMID- 15726167
TI  - Fluorometric sensing of the salt-induced B-Z DNA transition by combination of two
      pyrene-labeled nucleobases.
AB  - We have developed a new fluorescent DNA sensor containing two pyrene-labeled
      nucleobases, (Pet)G and (Py)C, and the fluorescence color was altered by the salt
      induced B-Z DNA transition.

PMID- 15726169
TI  - A computational study of the reactions of a beta-diketiminatoaluminium(I) complex
      with the hydrogen atom and the electron.
AB  - A computational study has been performed to examine the reactions of a model beta
      diketiminatoaluminium (I) complex with the hydrogen atom and with the electron.
      It was found that the hydrogen atom adds to the metal centre exothermically
      (DeltaH(rxn)=-202 kJ mol(-1)), and the spin density in the resulting radical
      resides entirely on the beta-diketiminato ligand. The spin density of the
      corresponding radical anion is very similar to the H-adduct.

PMID- 15726170
TI  - Metal induced selectivity in phosphate ion binding in E9 DNase.
AB  - Mass spectrometric and calorimetric data reveal that phosphate ion binding to the
      active site of colicin E9 DNase is delicately regulated by concomitant binding of
      specific transition metal ions.

PMID- 15726171
TI  - One-dimensional void-space arrays constructed from a coordination polymer with
      bowl-like frameworks of cavitands.
AB  - A one-dimensional coordination polymer of [Mn(II)(hfac)2] bridged by new bowl
      like ligands of cavitands was prepared and the crystal structure was determined
      by X-ray crystal analysis. Ethyl acetate molecules are necessarily included as
      guest molecules in each of the void-space cavities of the cavitands, and then are
      held by weak interaction forces.

PMID- 15726172
TI  - A new type of nonsulfide hydrotreating catalyst: nickel phosphide on carbon.
AB  - Nickel phosphide on carbon is successfully synthesized by temperature-programmed
      reduction as verified with X-ray diffraction and extended X-ray absorption fine
      structure measurements; it shows superior activity, selectivity, and stability
      for sulfur removal from the refractory compound 4,6-dimethyldibenzothiophene with
      a steady-state conversion of 99%, which is much higher than that of a commercial
      NiMoS/[gamma]-Al2O3 catalyst of 68%.

PMID- 15726173
TI  - Silica-supported lanthanide silylamides for methyl methacrylate polymerisation:
      controlled grafting induces controlled reactivity.
AB  - Lanthanide silylamides were grafted onto non-porous silica dehydroxylated at
      various temperatures, and the surface species nature and relative distribution
      were correlated with MMA polymerisation activity and selectivity.

PMID- 15726174
TI  - Group transfer polymerisation in hydrophobic ionic liquids.
AB  - For the first time, group transfer polymerisation of methyl methacrylate (MMA)
      has been successfully carried out at ambient temperatures in an ionic liquid to
      produce living polymers of improved polydispersity.

PMID- 15726175
TI  - 1,4-Cyclohexadienes as mechanistic probes for the Jacobsen epoxidation: evidence
      for radical pathways.
AB  - 1,4-Cyclohexadienes allow a direct comparison of epoxidation and C-H oxidation
      within the same molecule and give evidence for radical pathways during the
      Jacobsen epoxidation.

PMID- 15726176
TI  - Synthesis of deuterium labelled L- and D-glutamate semialdehydes and their
      evaluation as substrates for carboxymethylproline synthase (CarB)--implications
      for carbapenem biosynthesis.
AB  - Carboxymethylproline synthase was shown to condense L-glutamate semialdehyde with
      malonyl-coenzyme A to produce (2S,5S)-carboxymethylproline, while incubation of D
      glutamate semialdehyde results only in uncoupled turnover of malonyl-CoA.

PMID- 15726177
TI  - Morphology-controlled large-scale synthesis of ZnO nanocrystals from bulk ZnO.
AB  - Gram-scale, teardrop-like, monodisperse ZnO nanocrystals with a well-resolved
      absorption onset and a strong sharp UV emission were prepared by thermal
      decomposition of ZnO-oleic acid complexes in hexadecylamine.

PMID- 15726178
TI  - Poly(3,6-dimethoxy-thieno[3,2-b]thiophene): a possible alternative to poly(3,4
      ethylenedioxythiophene)(PEDOT).
AB  - Electropolymerization of the title compound leads to a conjugated polymer with
      redox potential, band gap, optical transparency in the doped state and stability
      similar to those of PEDOT.

PMID- 15726179
TI  - PS-IIDQ: an efficient polymer-supported amide coupling reagent.
AB  - Polystyrene-IIDQ is a polymer-supported coupling reagent that couples carboxylic
      acids to amines in good yields and high purity without the requirement of a pre
      activation step. Importantly the order of addition of the amine, acid or coupling
      agent makes no difference to the efficiency of the coupling reaction and the
      reagent can be readily regenerated.

PMID- 15726180
TI  - Photoinduced morphism of gemini surfactant aggregates.
AB  - The photochemical behaviour of an azobenzene chromophore inserted in a gemini
      surfactant imparts photocontrol to the resulting amphiphile assemblies, including
      the collapse, upon irradiation, of the multi lamellar vesicles formed in aqueous
      solution.

PMID- 15726181
TI  - Low-melting sugar-urea-salt mixtures as solvents for Diels-Alder reactions.
AB  - Sweet solutions are obtained upon heating mixtures of simple carbohydrates, urea
      and inorganic salts to moderate temperatures, to give new chiral media for
      organic reactions.

PMID- 15726182
TI  - Highly active and selective palladium catalyst for hydroesterification of styrene
      and vinyl acetate promoted by polymeric sulfonic acids.
AB  - Highly efficient, selective and recyclable palladium catalyst systems for
      hydroesterification of styrene and vinyl acetate were realized by using 1,2
      bis(di-tert-butylphosphinomethyl)benzene as ligand and polymeric sulfonic acids
      of limited SO(3)H loadings as promoter.

PMID- 15726183
TI  - Methoxycarbonylation of vinyl acetate catalysed by palladium complexes of
      bis(ditertiarybutylphosphinomethyl)benzene and related ligands.
AB  - High selectivities to methyl acetoxypropanoate esters (b : l up to 3.6 : 1) are
      obtained from the methoxycarbonylation of vinyl acetate catalysed by palladium
      complexes of bis(ditertiarybutylphosphinomethyl)benzene in the presence of acid,
      provided that the acid concentration does not exceed that of the free phosphine.

PMID- 15726184
TI  - Mupirocin W, a novel pseudomonic acid produced by targeted mutation of the
      mupirocin biosynthetic gene cluster.
AB  - Mutation of the mupW gene in the mupirocin biosynthetic gene cluster in
      Pseudomonas fluorescens results in efficient production of a novel pseudomonic
      acid metabolite, mupirocin W, which lacks the characteristic tetrahydropyran
      ring, and reveals the role of the mupW gene in pseudomonic acid biosynthesis.

PMID- 15726185
TI  - Monitoring the effect of ultrafast deactivation of the electronic excited states
      of DNA bases and polynucleotides following 267 nm laser excitation using
      picosecond time-resolved infrared spectroscopy.
AB  - In this paper we demonstrate the use of picosecond time-resolved infrared
      spectroscopy (ps-TRIR) to monitor the early structural dynamics of DNA bases and
      polydeoxynucleotides following UV excitation in solution.

PMID- 15726187
TI  - Effect of underlying coronene and perylene adlayers for [60]fullerene molecular
      assembly.
AB  - Supramolecularly assembled layers of C60 on coronene- and perylene-modified
      Au(111) surfaces were investigated and the structure of the C60 adlayer was found
      to be strongly influenced by the underlying organic layers, suggesting that the
      latter underlying organic adlayers play an important role in the process of
      formation of the C60 molecular adlayer.

PMID- 15726186
TI  - Ruthenium-catalyzed coupling of aldimines with arylboronates: new synthetic
      method for aromatic ketones.
AB  - Using the chelation strategy, the reaction of aldimines bearing the 3-picolin-2
      yl group with various arylboronates in the presence of a ruthenium catalyst
      furnished the corresponding ketimines in high yields for a short reaction time;
      the resulting ketimines were readily converted to ketones by hydrolysis.

PMID- 15726188
TI  - Polyoxoanions functionalized by diorganotin groups: the tetrameric, chiral
      tungstoarsenate(III), [{Sn(CH3)2(H2O)}2{Sn(CH3)2}As3(alpha-AsW9O33)4]21-.
AB  - The tetrameric, hybrid organic-inorganic tungstoarsenate(III)
      [{Sn(CH3)2(H2O)}2{Sn(CH3)2}As3(alpha-AsW9O33)4]21- is composed of four (B-alpha
      AsW9O33) fragments that are linked by three dimethyltin groups and three As(III)
      atoms resulting in an unprecedented, chiral polyoxoanion assembly with C1
      symmetry.

PMID- 15726189
TI  - Regioselective insertion of 2-vinylpyridine in niobium and tantalum aryloxide
      complexes: an alternate route to pyridylalkyl metallacycles.
AB  - A series of niobium and tantalum aryloxide complexes containing pyridylethyl
      ligation have been synthesized via 2-vinylpyridine insertion to metal hydride
      complexes.

PMID- 15726190
TI  - Structural inversion in 3-D hexagonal organization of coil-rod-coil molecule.
AB  - We report an unusual example of supramolecular structural inversion in coil-rod
      coil molecules, from organized coil perforations in a rod layers to organized
      discrete rod-bundles in a coil matrix, while maintaining a 3-D hexagonal
      superlattice.

PMID- 15726191
TI  - Fabrication of mesoporous polymer using soft template method.
AB  - Mesoporous polymer materials were fabricated from micelle/polymer precursors
      prepared by the micelle template method in reverse microemulsion systems and the
      pore size could be tuned by varying the type and concentration of surfactant.

PMID- 15726192
TI  - Enhanced reactivity in OH/NH/pi polyfunctional systems through coupled
      proton/electron transfer in the excited state: the photocyclisation of 2-allyl-3
      aminophenol.
AB  - The photocyclisation rate of 2-allyl-3-(or 5-)aminophenols (1, 4 and 8) is
      dramatically enhanced, when compared with reference compounds, as a consequence
      of a coupled proton/electron transfer process.

PMID- 15726193
TI  - Highly efficient recycling of a "sandwich" type polyoxometalate oxidation
      catalyst using solvent resistant nanofiltration.
AB  - A "sandwich" type polyoxometalate catalyst ([MeN(n-C8H17)3]12[WZn3(ZnW9O34)2])
      was very efficiently recycled by nanofiltration with almost quantitative
      retention, using an alpha-alumina supported mesoporous gamma-alumina membrane.

PMID- 15726194
TI  - Enantioselective epoxidation of unfunctionalised olefins catalyzed by Mn(salen)
      complexes immobilized in porous materials via phenyl sulfonic group.
AB  - Heterogeneous chiral Mn(salen) catalysts axially immobilized on mesoporous
      materials via phenyl sulfonic groups result in remarkably higher ee values (up to
      95%) for asymmetric epoxidation of unfunctionalised olefins.

PMID- 15726195
TI  - New CO tolerant electro-catalysts exceeding Pt-Ru for the anode of fuel cells.
AB  - Novel types of CO tolerant electro-catalysts from Pt and organic metal complexes
      that are far superior to Pt-Ru and practically usable as anode catalysts in
      reformate gas fuel cells with 100 ppm CO tolerance have been developed.

PMID- 15726196
TI  - Photo-controllable tristability of a dithiolato-bipyridine-Pt(II) complex
      molecule containing two azobenzene moieties.
AB  - A new platinum complex with both an azo-bound dithiolato ligand and an azobenzene
      bound bipyridine ligand exhibits tristability reversibly controllable using
      different energy lights.

PMID- 15726197
TI  - Resonance stabilized bis-thiadiazinyl radicals.
AB  - The resonance stabilized bis-thiadiazinyl framework holds potential as a stable
      and versatile building block for the design of radical-based conductors and
      magnetic materials.

PMID- 15726198
TI  - First successful application of diphosphite ligands in the asymmetric
      hydroformylation of dihydrofurans.
AB  - Good enantioselectivities and excellent regioselectivities are achieved in the Rh
      catalyzed asymmetric hydroformylation of 2,5- and 2,3-dihydrofuran using
      diphosphite ligands; whereby the backbone of the ligand is crucial to suppressing
      isomerization and obtaining high ee's.

PMID- 15726199
TI  - Stepwise pattern modification of neuronal network in photo-thermally-etched
      agarose architecture on multi-electrode array chip for individual-cell-based
      electrophysiological measurement.
AB  - We have developed a procedure for stepwise topographical control of network
      patterns and neurite connection directions between adjacent living neurons using
      an individual-cell-based on-chip multi-electrode array (MEA) cell cultivation
      system with an agarose microchamber (AMC) array. This procedure enables flexible
      and precise control of the cell positions and easy and flexible control of the
      pattern modification of connections between the cells in AMCs through stepwise
      photo-thermal etching in which a portion of the agarose layer on the chip is
      melted with a 1480 nm infrared laser beam even during cultivation. With adequate
      laser power and this stepwise procedure, we can fabricate narrow micrometer-order
      grooves (microchannels) during cultivation in a stepwise manner. Using this
      procedure, we controlled the direction of elongation of axons and dendrites
      selectively and confirmed the direction by immunostaining. We also demonstrated
      electrophysiological one-way transmission of signals among aligned hippocampal
      neurons in which the directions of the neurite connections were controlled using
      this stepwise photo-thermal etching procedure. These results demonstrate the
      potential of full direction control of neurite connections between neurons using
      stepwise photo-thermal etching to form microchannels one by one in an on-chip
      AMC/MEA cell cultivation system. We can thus better understand the meaning of
      neuronal network patterns and connection directions.

PMID- 15726201
TI  - Protein adsorption in static microsystems: effect of the surface to volume ratio.
AB  - A numerical model for the adsorption kinetics of proteins on the walls of a
      microchannel has been developed using the finite element method (FEM) to address
      the coupling with diffusion phenomena in the restricted microchannel volume. Time
      evolutions of the concentration of one species are given, both in solution and on
      the microchannel walls. The model illustrates the adsorption limitation sometimes
      observed when the microdimensions of these systems induce a global depletion of
      the bulk solution. A new non-dimensional parameter is introduced to predict the
      final value of the coverage of any microsystem under static adsorption. A working
      curve and a criteria (h/K[Gamma](max) > 10) are provided in order to choose, for
      given adsorption characteristics, the value of the volume-to-surface ratio (i.e.
      the channel height h) avoiding depletion effects on the coverage (relative
      coverage greater than 90% of the theoretical one). Simulations were compared with
      confocal microscopy measurements of IgG antibody adsorption on the walls of a PET
      microchannel. The fit of the model to the experimental data show that the
      adsorption is under apparent kinetic control.

PMID- 15726200
TI  - Single-step affinity purification of toxic and non-toxic proteins on a fluidics
      platform.
AB  - Single-step fusion-based affinity purification of proteins with pH-controllable
      linkers was carried out in a fluidic device. The linkers were previously derived
      from self-splicing protein elements called inteins. Two different linkers were
      generated to solve two distinct separation problems: one for rapid single-step
      affinity purification of a wide range of proteins, and the other specifically for
      the purification of cytotoxic proteins. Scale-down factors of 185 resulted in
      separations in a 27 microl bed-volume. A rotating CD format was chosen because of
      its simplicity in effecting fluid movement through centrifugal force without the
      complications associated with electro-osmosis and other pumping methods. The
      design and fabrication of the fluidic device and the protein purification process
      are described. This work, which demonstrates the purification of active proteins
      by two distinct fluidic separations, is widely applicable to small-scale
      massively parallel proteomic separations.

PMID- 15726202
TI  - Application of microchip assay system for the measurement of C-reactive protein
      in human saliva.
AB  - In the last decade, saliva has been advocated as a non-invasive alternative to
      blood as a diagnostic fluid. However, use of saliva has been hindered by the
      inadequate sensitivity of current methods to detect the lower salivary
      concentrations of many constituents compared to serum. Furthermore, developments
      in the areas related to lab-on-a-chip systems for saliva-based point of care
      diagnostics are complicated by the high viscosity and heterogeneous properties
      associated with this diagnostic fluid. The biomarker C-reactive protein (CRP) is
      an acute phase reactant and a well-accepted indicator of inflammation. Numerous
      clinical studies have established elevated serum CRP as a strong, independent
      risk factor for the development of cardiovascular disease (CVD). CVD has also
      been associated with oral infections (i.e. periodontal diseases) and there is
      evidence that systemic CRP may be a link between the two. Clinical measurements
      of CRP in serum are currently performed with "high sensitivity" CRP (hsCRP)
      enzyme-linked immunosorbent assay (ELISA) tests that lack the sensitivity for the
      detection of this important biomarker in saliva. Because measurement of salivary
      CRP may represent a novel approach for diagnosing and monitoring chronic
      inflammatory disease, including CVD and periodontal diseases, the objective of
      this study was to apply an ultra-sensitive microchip assay system for the
      measurement of CRP in human saliva. Here, we describe this novel lab-on-a-chip
      system in its first application for the measurement of CRP in saliva and
      demonstrate its advantages over the traditional ELISA method. The increased
      sensitivity of the microchip system (10 pg ml(-1) of CRP with 1000-fold dilution
      of saliva sample) is attributed to its inherent increased signal to noise ratio,
      resulting from the higher bead surface area available for antigen/antibody
      interactions and the high stringency washes associated with this approach.
      Finally, the microchip assay system was utilized in this study to provide direct
      experimental evidence that chronic periodontal disease may be associated with
      higher levels of salivary CRP.

PMID- 15726204
TI  - Measuring reaction kinetics in a lab-on-a-chip by microcoil NMR.
AB  - A microfluidic chip with an integrated planar microcoil was developed for Nuclear
      Magnetic Resonance (NMR) spectroscopy on samples with volumes of less than a
      microliter. Real-time monitoring of imine formation from benzaldehyde and aniline
      in the microreactor chip by NMR was demonstrated. The reaction times in the chip
      can be set from 30 min down to ca. 2 s, the latter being the mixing time in the
      microfluidic chip. Design rules will be described to optimize the microreactor
      and detection coil in order to deal with the inherent sensitivity of NMR and to
      minimize magnetic field inhomogeneities and obtain sufficient spectral
      resolution.

PMID- 15726203
TI  - AC frequency characteristics of coplanar impedance sensors as design parameters.
AB  - Glass-based microchannel chips were fabricated using photolithographic
      technology, and Pt thin-film microelectrodes, as coplanar impedance sensors, were
      integrated on them. Longitudinal design parameters, such as interelectrode
      spacing and electrode width, of coplanar impedance sensors were changed to
      determine AC frequency characteristics as design parameters. Through developing
      total impedance equations and modeling equivalent circuits, the dominant
      components in each frequency region were illustrated for coplanar impedance
      sensors and the measured results were compared with fitted values. As the ionic
      concentration increased, the value of the frequency-independent region decreased
      and cut-off frequencies increased. As the interelectrode spacing increased, cut
      off frequencies decreased and total impedance increased. However, the width of
      each frequency-independent region was similar. As the electrode area increased,
      f(low) decreased but f(high) was fixed. We think that the decrease in R(Sol)
      dominated over the influence of other components, which resulted in heightening
      f(low) and f(high). The interelectrode spacing is a more significant parameter
      than the electrode area in the frequency characteristics of coplanar sensors. The
      deviation of experimentally obtained results from theoretically predicted values
      may result from the fringing effect of coplanar electrode structure and parasitic
      capacitance due to dielectric substrates. We suggest the guidelines of dominant
      components for sensing as design parameters.

PMID- 15726205
TI  - Efficient energy based modeling and experimental validation of liquid filling in
      planar micro-fluidic components and networks.
AB  - This paper presents a model that describes how liquid flow fills micro-fluidic
      components and networks. As an alternative to computational fluid dynamic (CFD)
      simulations, we use a constrained energy minimization approach. This approach is
      based on two assumptions that hold in many micro-fluidic devices: (i) The length
      scales are small, and we consider slow filling rates, hence fluid momentum and
      viscous terms are small compared to surface tension forces, consequently the
      liquid/gas interfaces can be viewed as a succession of quasi-steady equilibrium
      configurations. (ii) Any equilibrium configuration corresponds to a surface
      tension energy minima which is constrained by the device shape and the volume of
      liquid in the device. The model is developed for planar micro-fluidic devices, is
      based on a fundamental physical principle, and shows accurate agreement with
      experimental data. It takes us only a few minutes to evaluate the model for a
      planar component of any shape using the Surface Evolver software, and this is
      significantly less then the computer run time required for CFD simulations.
      Moreover, once a library of component models has been created (which takes less
      than an hour of computer time) it then takes only seconds to simulate different
      network architectures with thousands of components. This fast "reconfigure the
      network and simulate in seconds" capability is essential for the design of truly
      complex networks that will enable the next generation of passive, micro-fluidic,
      lab-on-a-chip systems.

PMID- 15726206
TI  - Thin chip microsprayer system coupled to quadrupole time-of-flight mass
      spectrometer for glycoconjugate analysis.
AB  - A thin chip polymer-based microsprayer has been coupled to a hybrid quadrupole
      time-of-flight mass spectrometer (QTOF MS) and introduced in carbohydrate
      research. The feasibility of the approach is demonstrated for mapping, sequencing
      and structural elucidation of glycoconjugates originating from human body fluids
      and tissues such as a glycopeptide mixture from normal human urine and an
      isolated and purified GT1 ganglioside fraction from normal adult human brain. The
      optimization procedure required by each glycoconjugate category is described and
      the advantages of the system in terms of flexibility and adaptability to QTOF MS,
      stability of the ESI MS signal, carbohydrate ionization and sequencing,
      sensitivity, speed of analysis and sample consumption are discussed.

PMID- 15726207
TI  - Planar chip device for PCR and hybridization with surface acoustic wave pump.
AB  - We have developed a microfluidic device operating at a planar surface instead of
      a closed channel network. The fluid is transported in single droplets using
      surface acoustic waves (SAW) on a piezoelectric LiNbO(3) substrate. The surface
      of the piezo is chemically structured to induce high contact angles of the
      droplets or enclose areas where the liquid can wet the substrate. Combining the
      SAW technique with thin film resistance heaters, a biological analysis chip with
      integrated DNA amplification by PCR and hybridization was designed. To prevent
      evaporation of the PCR reagents at high temperatures the sample is enclosed in
      droplets of mineral oil. On this chip the SAW resolves dried primers, shifts the
      oil capped liquid between the two heaters and mixes during hybridization. The
      chip is able to perform a highly sensitive, fast and specific PCR with a volume
      as low as 200 nl. During the temperature cycles an online monitoring of the DNA
      concentration is feasible with an optical unit, providing a sensitivity of 0.1
      ng. After PCR the product is moved to the second heater for the hybridization on
      a spotted DNA array. With our chip we were able to detect a single nucleotide
      polymorphism (SNP) responsible for the Leiden Factor V syndrome from human blood.

PMID- 15726208
TI  - Microfluidic solid phase suspension transport with an elastomer-based, single
      piezo-actuator, micro throttle pump.
AB  - We report a Micro Throttle Pump (MTP) which has been shown to pump 5 microm
      diameter polystyrene beads at a concentration of 4.5 x 10(7) beads ml(-1). This
      new MTP design is constructed in a straightforward manner and actuated by a
      single piezoelectric (PZT) element. Maximum flow rates at 800 Hz drive frequency
      of 132 microl min(-1) with water and 108 microl min(-1) with a bead suspension
      were obtained. Maximum back-pressures of 6 kPa were observed in both cases. The
      reported MTP employs specific location of distinct internal microfluid structures
      cast in a single compliant elastomeric substrate to exploit the opposing
      directions of flexure of regions of a piezoelectric-glass composite bonded to the
      elastomer. By this novel means, distinct flexural regions, exhibiting compressive
      and tensile stresses respectively, allow both the pump's integrated input and
      output throttles and its pump chamber to be actuated concurrently by a single
      PZT. To support MTP design we also report the characterisation of an individual
      throttle's resistance as a function of actuator deflection and discuss the
      underlying mechanism of the throttling effect.

PMID- 15726209
TI  - Fabrication and characterization of high-temperature microreactors with thin film
      heater and sensor patterns in silicon nitride tubes.
AB  - In this paper the fabrication and electrical characterization of a silicon
      microreactor for high-temperature catalytic gas phase reactions, like Rh
      catalyzed catalytic partial oxidation of methane into synthesis gas, is
      presented. The microreactor, realized with micromachining technologies, contains
      silicon nitride tubes that are suspended in a flow channel. These tubes contain
      metal thin films that heat the gas mixture in the channel and sense its
      temperature. The metal patterns are defined by using the channel geometry as a
      shadow mask. Furthermore, a new method to obtain Pt thin films with good adhesive
      properties, also at elevated temperatures, without adhesion metal is implemented
      in the fabrication process. Based on different experiments, it is concluded that
      the electrical behaviour at high temperatures of Pt thin films without adhesion
      layer is better than that of Pt/Ta films. Furthermore, it is found that the
      temperature coefficient of resistance (TCR) and the resistivity of the thin films
      are stable for up to tens of hours when the temperature-range during operation of
      the microreactor is below the so-called "burn-in" temperature. Experiments showed
      that the presented suspended-tube microreactors with heaters and temperature
      sensors of Pt thin films can be operated safely and in a stable way at
      temperatures up to 700 degrees C for over 20 h. This type of microreactor solves
      the electrical breakdown problem that was previously reported by us in flat
      membrane microreactors that were operated at temperatures above 600 degrees C.

PMID- 15726210
TI  - Single molecule studies of quantum dot conjugates in a submicrometer fluidic
      channel.
AB  - A microfluidic and optical system was created for the detection and analysis of
      single molecules in solution. Fluidic channels with submicrometer dimensions were
      used to isolate, detect and identify individual quantum dots conjugated with
      organic fluorophores. The channels were fabricated in fused silica with a 500 nm
      square cross section. The resulting focal volume of approximately 500 aL reduced
      fluorescent background and increased the signal to noise ratio of single molecule
      detection. The channels also enabled the rapid detection of 99% of quantum dots
      and organic fluorophores traversing the focal volume. Conjugates were driven
      through the channels electrokinetically at 2.3 kV cm(-1), excited with a single
      476 nm wavelength laser and detected with a confocal microscope. Fluorescence
      emission was collected simultaneously from green (500-590 nm) and red (610-680
      nm) regions of the spectrum. Signal rejection was minimized by the narrow and
      symmetric emission spectra of the quantum dots. To demonstrate efficient
      multicolor detection and characterization of single molecule binding, Qdot 655
      Streptavidin Conjugates were bound to Alexa Fluor 488 molecules and individually
      detected. Photon counting histogram analysis was used to quantify coincident
      detection and degree of binding. Fluorescence correlation spectroscopy was used
      to measure the mobility of bound and unbound species. The union of fluidic
      channels with submicrometer dimensions and quantum dots as fluorescent labels
      resulted in efficient and rapid multiplexed single molecule detection and
      analysis.

PMID- 15726211
TI  - Chembio extraction on a chip by nanoliter droplet ejection.
AB  - This paper describes a novel liquid separation technique for chembio extraction
      by an ultrasonic nanoliter-liquid-droplet ejector built on a PZT sheet. This
      technique extracts material from an aqueous two-phase system (ATPS) in a precise
      amount through digital control of the number of nanoliter droplets, without any
      mixing between the two liquids in the ATPS. The ultrasonic droplet ejector uses
      an acoustic streaming effect produced by an acoustic beam focused on the liquid
      surface, and ejects liquid droplets only from the liquid surface without
      disturbing most of the liquid below the surface. This unique characteristic of
      the focused acoustic beam is perfect (1) for separating a top-layer liquid (from
      the bulk of liquid) that contains particles of interest or (2) for recovering a
      top-layer liquid that has different phase from a bottom-layer liquid. Three kinds
      of liquid extraction are demonstrated with the ultrasonic droplet ejector: (1) 16
      microl of top layer in Dextran-polyethylene glycol-water ATPS (aqueous two-phase
      system) is recovered within 20 s; (2) micron sized particles that float on water
      surface are ejected out with water droplets; and (3) oil layer on top of water is
      separated out.

PMID- 15726212
TI  - Microfluidic operations using deformable polymer membranes fabricated by single
      layer soft lithography.
AB  - We show that it is possible to use single layer soft lithography to create
      deformable polymer membranes within microfluidic chips for performing a variety
      of microfluidic operations. Single layer microfluidic chips were designed,
      fabricated, and characterized to demonstrate pumping, sorting, and mixing. Flow
      rates as high as 0.39 microl min(-1) were obtained by peristaltic pumping using
      pneumatically-actuated membrane devices. Sorting was attained via pneumatic
      actuation of membrane units placed alongside the branch channels. An active mixer
      was also demonstrated using single-layer deformable membrane units.

PMID- 15726213
TI  - Role of urinary screening programmes in children in the prevention of chronic
      kidney disease.
AB  - INTRODUCTION: This article reviews published literature on the usefulness of
      population-based urinary screening in the Asian paediatric population. METHODS:
      Articles were found in the Medline database using the key words "paediatrics",
      "urine screening", "proteinuria", "haematuria" and "population". The Asian
      countries which had carried out population-based urinary screening of the
      paediatric population included Taiwan, Japan and Korea. One study was found on
      urinary screening in a select population in Malaysia. Preliminary results of the
      urinary screening of school children in Singapore are presented and compared with
      the results found in the above-mentioned countries. RESULTS: Overall, the
      proportion of children found to have urinary abnormalities ranged from less than
      0.1% of the population screened to almost 50% of a select cohort referred from
      the screening programmes for the evaluation of urinary abnormalities. In the
      pilot Singapore school screening programme, the prevalence of clinically
      significant proteinuria was 1.25 per 1000 children screened. Multivariate
      analysis showed that low body weight was associated with a 1.8-fold greater risk
      for proteinuria. The major cause of haematuria and proteinuria in those studies
      where renal biopsies were performed was glomerulonephritis. The Taiwanese
      experience also showed a reduction in the incidence of end-stage renal failure
      diagnosed in children after the onset of urine screening. CONCLUSION: These
      studies showed that urinary screening programmes in school children allow the
      early detection of disease. The cost-benefit ratio for specific populations
      should be determined before the implementation of such programmes.

PMID- 15726214
TI  - Progression of renal failure -- the role of hypertension.
AB  - High blood pressure plays a key role in the progression of renal failure.
      Hypertension is a common presentation of kidney disease and an almost invariable
      accompaniment of renal failure. Hypertension is also a major contributor to
      cardiovascular disease, the major cause of morbidity and mortality in renal
      failure. Hypertension is both cause and consequence of renal failure, but the
      precise nature and prevalence of hypertensive nephrosclerosis as a cause of renal
      failure remains controversial. There is strong evidence that hypertension
      accelerates the progression of experimental renal disease and that control of
      blood pressure is effective in preventing this progression. Hypertension, both
      accelerated and "benign" (a misnomer), has long been recognised as a poor
      prognostic feature in human renal disease and more recently in renal allograft
      survival. Blood pressure control is very effective in retarding renal disease
      progression. There are compelling indications for angiotensin-converting enzyme
      inhibitors in both non-diabetic and type 1 diabetic nephropathies, and for
      angiotensin receptor blockers in type 2 diabetic nephropathy. Most patients will
      require combination drug therapy to control blood pressure and reduce both
      progression of renal failure and the associated cardiovascular morbidity and
      mortality.

PMID- 15726215
TI  - Retardation of kidney failure -- applying principles to practice.
AB  - Over the next decade, the number of patients with end-stage renal disease (ESRD)
      treated by dialysis may double, and even developed nations will have difficulty
      in coping with this alarming increase. This review will outline the proven and
      unproven strategies that have the potential to retard the progression of chronic
      kidney disease (CKD). Recently, a number of randomised clinical trials have
      demonstrated the efficacy of several strategies to slow the progression of CKD.
      Proven strategies include adequate blood pressure control (with angiotensin
      blockade), and for diabetic nephropathy good glycaemic control. Other potentially
      beneficial strategies include smoking cessation, lipid control and aldosterone
      blockade. The early institution of these strategies has the potential to regress
      established CKD as well as improve the long-term cardiovascular outcomes of these
      patients. Proof of the efficacy in humans of promising experimental approaches,
      such as the administration of growth factors (e.g., recombinant bone
      morphogenetic protein-7), anti-fibrotic agents (e.g., pirfenidone) and novel anti
      proteinuric drugs (e.g., pentosan polysulphate), is awaited. Finally, the primary
      prevention of CKD, at least in part, by the eradication of type 2 diabetes and
      obesity (through improvement of lifestyle factors), and adequate treatment of
      hypertension, have the potential to eliminate up to half of the most common
      causes of CKD (or ESRD) in developed countries.

PMID- 15726216
TI  - Retarding the progression of diabetic nephropathy in type 2 diabetes mellitus:
      focus on hypertension and proteinuria.
AB  - INTRODUCTION: There is a worldwide pandemic of type 2 diabetes mellitus and
      approximately one-third of these individuals will develop diabetic nephropathy.
      Coupled with their increased risk for cardiovascular disease, these individuals
      pose an enormous economic and social burden to all countries. This review will
      discuss therapeutic strategies, aimed at control of blood pressure and
      proteinuria, to prevent or retard the development of diabetic nephropathy.
      METHODS: Studies that involved patients with type 2 diabetes with albuminuria
      (microalbuminuria or proteinuria) and/or hypertension and/or renal impairment
      were included in this review. The PubMed Medline database was used as the source
      of data. RESULTS: Blood pressure control is paramount in reducing cardiovascular
      risk and the development of diabetic nephropathy. The target blood pressure is
      <130/80 mm Hg in all patients with type 2 diabetes. Angiotensin receptor blockers
      (ARBs) are the preferred first-line agents while angiotensin-converting enzyme
      (ACE) inhibitors can be considered in those with microalbuminuria and
      normoalbuminuria. Reduction in proteinuria retards the progression of nephropathy
      and should be considered as a goal on its own. Dual therapy with an ACE inhibitor
      and ARB can be considered in patients with severe proteinuria or uncontrolled
      hypertension. CONCLUSION: Important strategies to prevent or retard the
      progression of diabetic nephropathy in type 2 diabetes include excellent blood
      pressure control with an aggressive approach to reduce microalbuminuria or
      proteinuria. The drugs of choice are the ARB and the ACE inhibitor.

PMID- 15726217
TI  - Hyperlipidaemia in chronic kidney disease.
AB  - Cardiovascular disease is a major cause of mortality and morbidity in patients
      with chronic kidney disease (CKD). The prevalence of hyperlipidaemia or
      dyslipidaemias is much higher compared to the general population. Total or low
      density lipoprotein (LDL) cholesterol is highest in patients with chronic renal
      impairment. The majority of patients with CKD do not develop renal failure;
      indeed, most of them die of cardiovascular causes before the development of renal
      failure. The K/DOQI (Kidney Disease Outcomes Quality Initiative) guidelines on
      dyslipidaemias in CKD suggest that all patients should therefore be evaluated for
      dyslipidaemias. They should have a complete fasting lipid profile with total, LDL
      and high-density lipoprotein cholesterol, and triglycerides measured to identify
      those at risk and those who require treatment. Generally, the treatment approach
      parallels that suggested by the National Cholesterol Education Program Adult
      Treatment Panel III guidelines, in which the main focus of treatment is the level
      of LDL cholesterol. Patients with CKD should be considered a "very high risk"
      category and aggressive therapeutic intervention initiated to reduce the risk of
      cardiovascular events.

PMID- 15726218
TI  - Preventing renal transplant failure.
AB  - INTRODUCTION: Allograft failure due to immunological or non-immunological causes
      or a combination and patient death after transplantation are the 2 major causes
      of renal transplant loss. This paper reviews the various causes of allograft
      failure and explores strategies for its prevention. RESULTS: Immune mechanisms of
      renal allograft failure are those mediated by acute and chronic rejection and are
      initiated by human leukocyte antigen (HLA) disparity between donor and recipient
      and increased recipient immune responsiveness that results in pre-sensitisation
      against HLA antigens. Better HLA matching between donor and recipient in both
      live-donor and cadaveric renal transplant recipients and the use of more potent
      immunosuppressants has reduced the incidence of acute rejection and resulted in
      improved overall graft survivals in recent years. However, as the use of more
      potent immunosuppression increases the risk of infections and malignancy,
      tailoring therapy by administering more potent immunosuppression to those at
      higher immunological risk may result in a better balance between the risks and
      benefits of immunosuppressive therapies. Ischaemia of the donor kidney,
      calcineurin inhibitor (CNI), mediated nephrotoxicity, reduced renal mass,
      hypertension, hyperlipidaemia and infections contribute to allograft failure
      through non-immunological mechanisms. Indeed, any cause of renal injury that
      results in nephron loss, either immunological or non-immunological, leads to
      reduced renal mass and initiates further renal damage due to hyperfiltration.
      Optimising these factors and minimising CNI nephrotoxicity are critical in
      reducing chronic allograft failure. CONCLUSIONS: Optimising each of these time
      dependent and immunosuppressive drug-related factors would allow the maximization
      of renal allograft function and survival.

PMID- 15726219
TI  - Herbal treatment for renal diseases.
AB  - Renal fibrosis is a common consequence of chronic kidney diseases (CKD). Standard
      therapy to prevent progression of CKD in western medicine includes dietary
      protein restriction, blood pressure control, angiotensin-converting enzyme
      inhibition and angiotensin receptor blockade. However, little is known about the
      renoprotective effects of Chinese herbal medicine. Cumulative evidence suggests
      that some Chinese herbal medicines, including Astragalus and a mixture of
      Astragalus plus Angelica, Ligusticum, Triptolide and Rhubarb, have a beneficial
      role in slowing the progression of CKD. This effect is multi-functional and multi
      targeted, and is often associated with a reduction in proteinuria and the
      amelioration of dyslipidaemia, but not with changes in systemic blood pressure.
      These mechanisms include anti-inflammation and inhibition of TGF-b
      overproduction. On the other hand, some Chinese herbal medicines may be hazardous
      to patients with renal diseases. In this review, we discuss recent advances in
      the research of some Chinese herbs for pharmacological intervention of
      progressive renal diseases and kidney-related injuries.

PMID- 15726220
TI  - ATRA therapy restores normal renal function and renal reserve and prevents renal
      failure.
AB  - This article presents clinical data which suggest that the current dosage of
      losartan 50 to 100 mg/day may not be the optimum in many cases, especially if
      used as monotherapy in the treatment of proteinuria and we may have to increase
      to 200 mg/day. However, about 30% of patients cannot take angiotensin-converting
      enzyme inhibitor (ACEI) because of the side effect of cough. To potentiate the
      anti-proteinuric effect of losartan, especially for patients who do not adhere to
      a low salt diet, a 12.5-mg dose of hydro-chlorothiazide may further decrease
      proteinuria. The main message of this article is that we would have to, in many
      instances, increase the dose of losartan to a minimum of 100 mg/day or 100 mg
      twice a day for some patients for optimal therapy. The second message is to
      monitor the creatinine clearance test (CCT) and to start therapy when CCT is
      reduced and not wait for serum creatinine to rise to abnormal levels (renal
      impairment) before starting therapy. The first group involves half a dozen
      patients with hypertension but no proteinuria. Therapy with losartan is shown to
      improve the renal function. This data suggest that losartan, apart from its use
      in reduction of proteinuria, can be used in patients with mild renal impairment
      without proteinuria to reverse the mild renal impairment and preserve renal
      function. The second group deals with 3 patients with low creatinine clearance.
      After a followup period of an average of 3 years, they all developed renal
      impairment. In another 6 patients, the data suggest that we should perhaps treat
      patients with low CCT as soon as possible and with dose ranging from 100 to 200
      mg/day if necessary, to derive maximum beneficial effect. The third group
      highlights 5 patients with high CCT due to glomerular hyperfiltration. With time,
      the high CCT decreases and renal impairment sets in. The data suggest that
      patients with high CCT should be treated early to prevent renal impairment. The
      fourth group illustrates 6 patients where their proteinuria was markedly reduced
      with the increase of losartan from 100 mg/day to 200 mg/day, suggesting that
      losartan 200 mg/day is probably the optimum dose. In conclusion, apart from its
      traditional usage in reduction of proteinuria to retard progression to renal
      failure, the data suggest that losartan is also indicated in patients with renal
      impairment in the absence of proteinuria; patients with low CCT, patients with
      high CCT and patients who do not respond to a dosage of 100 mg/day should have
      the dosage increased to 100 mg twice daily to increase efficacy of losartan. It
      is hoped that with these new and earlier indications as well as increased dosage
      of losartan starting with 100 mg, whenever possible, and increasing to 200
      mg/day, if there is no response, we can prevent more patients from developing
      renal failure. Based on these observations, further randomised controlled trials
      should be designed to address these issues.

PMID- 15726221
TI  - Incidence and predictors of falls in the chinese elderly.
AB  - INTRODUCTION: This is the first prospective longitudinal study carried out in a
      Chinese elderly population with the objective of identifying the incidence and
      predictors of falls. MATERIALS AND METHODS: This is a population-based cohort
      study in Hong Kong with 1517 ambulatory elderly Chinese recruited using a multi
      stage sampling method. Baseline data on demographic, comorbid diseases, drugs,
      Activities of Daily Living (ADL) [Barthel Index and Lawton's Instrumental
      Activities of Daily Living (IADL)], Geriatric Depression Scale (GDS-15),
      cognitive assessment by the Abbreviated Mental Test (AMT), fear of falling, self
      perceived mobility problem, hand grip strength, lower limb power, balance and
      gait tests were performed. Every subject was followed up for 1 year. RESULTS:
      Four hundred and one falls occurred in 294 fallers (19.3%) over 1 year of follow
      up. The prevalence of falls and recurrent falls were 19.3% and 4.75%,
      respectively. The incidences of falls (i.e., the fall events) were 220, 324 and
      270 per 1000 person-years for men, women and both gender, respectively. The
      independent predictors of falls were previous history of falls, advancing age,
      Parkinson's disease, knee extension power and gait speed. The independent
      predictors of recurrent falls were previous history of falls, self-perceived
      mobility problem, the knee extension strength and the Total Mobility Score of the
      Tinetti Balance and Gait Evaluation. CONCLUSIONS: The incidence of falls in the
      Chinese elderly was 270 per 1000 person-years. History of falls, old age,
      Parkinson's disease, decreased lower limb power and impairment in balance and
      gait function were important independent predictors of falls or recurrent falls
      in the Chinese elderly. Effective fall prevention programmes targeted at
      improving these risk factors for falls should be developed for the Chinese
      elderly in Hong Kong and Asia.

PMID- 15726222
TI  - SMN1 deletions among singaporean patients with spinal muscular atrophy.
AB  - INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive
      neuromuscular disorder characterised by degeneration of spinal cord anterior horn
      cells, leading to muscular atrophy. It is the second most frequent autosomal
      recessive disease among Caucasian populations with a prevalence of between 1 in
      6000 and 1 in 10,000 live births, and a carrier frequency of about 1 in 50. The
      International SMA Consortium classification defines several types of SMA
      depending on the age of onset and clinical severity. In the past, the diagnosis
      of SMA was confirmed by muscle biopsy and, sometimes, electromyography. In 1990,
      SMA was linked to the 5q13 region of chromosome 5. In 1995, it was found that
      >95% of patients with SMA have homozygous deletions of exons 7 and 8 of the
      survival motor neurone 1 (SMN1) gene, one of the candidate genes identified
      within 5q13. The purpose of our study was to determine the frequency of SMN1
      deletions in patients with known SMA and the impact of this on the diagnosis of
      SMA. MATERIALS AND METHODS: Molecular analysis was performed on stored DNA and
      case notes were reviewed retrospectively. RESULTS: Twenty-two (91.7%) out of 24
      patients with all types of SMA were homozygously deleted for exons 7 and/or 8 of
      SMN1. We also report our experience with prenatal diagnosis of SMA. CONCLUSIONS:
      Molecular studies can replace conventional investigations for SMA and have made
      the option of prenatal diagnosis possible for couples at risk.

PMID- 15726223
TI  - Uterine artery embolisation for symptomatic fibroids in a tertiary hospital in
      Singapore.
AB  - INTRODUCTION: Transcatheter uterine artery embolisation (UAE) for the treatment
      of symptomatic uterine enlargement due to fibroids has been performed in several
      overseas centres with promising results. We report our experience with UAE in
      Singapore General Hospital. MATERIALS AND METHODS: Twenty women with symptomatic
      uterine fibroids who declined surgery were treated by transcatheter UAE. The
      uterine arteries were selectively catheterised and embolised with polyvinyl
      alcohol particles. Post-procedure analgesia was administered via a patient
      controlled analgesia pump. The patients were followed up at regular intervals
      clinically and with transabdominal ultrasonography. RESULTS: Transcatheter UAE
      was performed on all patients with no major complications. Nineteen patients had
      both uterine arteries embolised while 1 patient had only the right uterine artery
      embolised on account of hypoplasia of the left uterine artery. The mean hospital
      stay was 3.5 days (range, 2 to 9). At a mean follow-up of 56 weeks (range, 6 to
      168), all patients reported improvements in their presenting symptoms. Objective
      improvement in terms of reduction of uterine and fibroid sizes was determined on
      ultrasonography. The median size of the uterine volume decreased from 308 to 187
      mL while the median diameter of the largest fibroid reduced from 6.2 to 4.6 cm.
      The median haemoglobin level increased to 12.7 g/dL from the pre-procedural
      median of 9.9 g/dL. One patient, who initially responded with a decrease in
      uterine and dominant fibroid size, became symptomatic (menorrhagia) at 6 months
      post-embolisation. She underwent a repeat procedure with complete resolution of
      symptoms. A second patient had recurrence of symptoms at 12 months, but was
      subsequently lost to follow-up. CONCLUSION: Mid-term results of UAE for the
      treatment of symptomatic fibroids in our hospital indicate this to be a safe and
      effective therapeutic option.

PMID- 15726224
TI  - Measurable predictive factors for progression to AIDS among HIV-infected patients
      in Singapore.
AB  - INTRODUCTION: This study identifies measurable factors at the time of diagnosis
      that predict the progression to Acquired Immunodeficiency Syndrome (AIDS) among
      Human Immunodeficiency Virus (HIV)-infected patients in Singapore. MATERIALS AND
      METHODS: We carried out a retrospective study of 790 HIV-infected patients from
      16 May 1985 to 31 December 2001. The end-point was the onset of AIDS-defining
      illness listed in the 1987 and 1991 revised Centers for Disease Control and
      Prevention criteria, but excluded CD4 cell counts as a criterion. Using the
      Kaplan-Meier method, AIDS-free survival curves were plotted for age groups at
      diagnosis, baseline CD4 counts and periods for utilisation of antiretroviral
      treatment. A Cox regression model was constructed to determine independent
      predictors of disease progression. RESULTS: Univariate analysis showed that
      patients of older age at diagnosis had a significantly higher risk of progression
      compared to younger patients, and patients with higher baseline CD4 cell counts
      had a lower risk of progression to AIDS. Adjusting for the simultaneous influence
      of several covariates on the rate of HIV progression to AIDS, multivariate
      analysis using the Cox model showed a significantly higher risk of progression
      for older patients at diagnosis, and the progressive lowering of risk with
      increasing baseline CD4 cell counts. CONCLUSIONS: This study found older age at
      diagnosis and baseline CD4 cell counts to be measurable predictors for HIV
      progression to AIDS at time of diagnosis. Identification of these risk factors
      enables physicians to provide counselling and advice, and to start appropriate
      treatment early. This could lower the risk of progression and improve survival.

PMID- 15726225
TI  - Narcolepsy in Singapore: is it an elusive disease?
AB  - INTRODUCTION: The aims of the study were to determine the demographic, clinical,
      and polysomnographic characteristics of narcolepsy, and to address the
      difficulties in diagnosing narcolepsy and cataplexy, which is a cardinal symptom.
      We also ventured to investigate the differences between narcolepsy with and
      without cataplexy. MATERIALS AND METHODS: Data were collected retrospectively
      from patients diagnosed with narcolepsy at the Sleep Disorder Unit of Singapore
      General Hospital over 5 years. Each patient had had a detailed clinical
      evaluation and overnight polysomnography (PSG) followed by a multiple sleep
      latency test (MSLT). RESULTS: A total of 28 cases were studied. Males made up
      85.7% of the total and females, 14.3%. The mean age was 30.9 years. All had
      excessive daytime sleepiness. Other manifestations were cataplexy (48.1%), sleep
      paralysis (51.9%), hypnogogic hallucinations (84%), disturbed night sleep
      (29.2%), automatisms (17.4%) and catnaps (95.8%). The mean duration of symptoms
      was 7.24 years. In the MSLT, the mean values for mean sleep latency and number of
      sleep onset rapid eye movement (REM) periods (SOREMP) were 4.3 minutes and 2.7,
      respectively. Narcolepsy was associated with obstructive sleep apnoea and
      periodic limb movement disorder (35.7%). All the variables were compared between
      those who had narcolepsy with cataplexy and without cataplexy. The duration of
      presenting complaint, REM latency, respiratory disturbance index, number of
      SOREMPs and the presence of sleep paralysis were significantly different in the 2
      groups. CONCLUSIONS: Narcolepsy predominantly affects young males. Concurrence of
      other sleep disorders is not uncommon. Some differences are evident between those
      who have narcolepsy with and without cataplexy.

PMID- 15726226
TI  - A two-stage approach identifies a Q344X mutation in the rhodopsin gene of a
      Chinese Singaporean family with autosomal dominant retinitis pigmentosa.
AB  - INTRODUCTION: Retinitis pigmentosa (RP) is a group of hereditary retinal diseases
      in which photoreceptor cells degenerate. It is both clinically and genetically
      heterogenous. Using a two-stage approach by combining linkage analysis with
      mutation detection, we have rapidly identified the gene locus and the mutation
      site of a Chinese Singaporean family with autosomal dominant RP. MATERIALS AND
      METHODS: Three Chinese Singaporean families were tested. One family showed
      autosomal dominant inheritance pattern, while the other two could be recessive or
      sporadic. Twelve di-nucleotide markers tightly linked to 6 genes known to be
      responsible for either autosomal dominant or recessive RP were selected for
      linkage analysis. Cosegregation of marker and disease inheritance pattern permits
      identification of the target candidate gene. RFLP (restriction fragment length
      polymorphism) markers were added to confirm the linkage result prior to the
      detailed mutation detection study. RESULTS: With this two-stage strategy, the
      autosomal dominant RP family showed the rhodopsin locus segregating concordantly
      with the disease. Mutation screening later identified a nonsense mutation 5261C>T
      in the last exon of rhodopsin gene. It predicted a Q344X changes at the C
      terminus of the gene product, truncating it by 5 amino acids. CONCLUSION: This
      systematic approach facilitates molecular diagnosis of a genetically heterogenous
      disease like RP. This is the first report of an RP mutation in Singapore. This
      5261C>T mutation has been reported in the Caucasian, but not the Chinese
      population. The relatively milder phenotype in this family showed similarity to
      the reported US family, indicating the correlation of mutation site to severity
      of disease regardless of ethnicity.

PMID- 15726227
TI  - Community psychiatry in Singapore: a pilot assertive community treatment (ACT)
      programme.
AB  - Severe mental illnesses cause their sufferers dismal functional impairment. The
      Global Burden of Disease lists schizophrenia among the top 10 contributors to
      health burden and disability around the world. In the Institute of Mental Health
      (IMH) of Singapore, 9 out of 10 Class-C beds are occupied by patients whose
      hospitalisation periods last 300 days on average. Whilst de-institutionalisation
      has not seen its expected level of success overseas, the provision of community
      based psychiatric care has been shown to be more cost-effective than hospital
      based inpatient care. As such, there is a need for increased emphasis on
      community psychiatric services, both to provide and to effectively utilise
      available resources to assist patients with severe mental illnesses in living and
      functioning within the community. In line with several other efforts, a pilot
      Assertive Community Treatment or ACT Programme was launched by IMH in November
      2003. This article details the aims, set-up and services of this pilot project
      funded by the Health Service Development Programme (HSDP) for 3 years, which
      receives referrals from IMH psychiatrists. With the services provided by the ACT
      team including psychosocial rehabilitation, it is hoped that patients will
      continue to receive adequate psychiatric care as well as maintain sufficient
      skills for self-care and independent living within the community despite the well
      documented deteriorating course of psychotic illnesses like schizophrenia.

PMID- 15726228
TI  - Infectious respiratory illnesses and their impact on healthcare workers: a
      review.
AB  - Respiratory illnesses are increasingly recognised as a growing concern for
      healthcare workers (HCWs) and patients. The recent hospital-based outbreak of
      Severe Acute Respiratory Syndrome (SARS) has once again highlighted the
      vulnerability of HCWs. The new epidemic of the 21st century resulted in
      tremendous economic and psychological impact with its high rates of mortality and
      nosocomial transmission. Even as the epidemic was brought under control within
      months, many details about the SARS coronavirus remained a mystery. The threat of
      another potential global outbreak continues to lurk in the background. Many
      valuable lessons have been learned through the SARS epidemic. It is, therefore,
      timely for us to review some of the respiratory pathogens that are well-known to
      cause nosocomial outbreaks. We need to be better armed to deal with future
      potential outbreaks and biohazardous situations. The importance of safeguarding
      the health of our medical staff and the community cannot be over-emphasised. In
      this paper, we review the incidence, transmission and various preventive
      strategies of respiratory illnesses in HCWs, in particular, new diagnostic tools,
      infection control management strategies, personal protective equipments,
      vaccination programmes and post-exposure prophylaxis.

PMID- 15726229
TI  - Periodontal disease -- the emergence of a risk for systemic conditions: pre-term
      low birth weight.
AB  - This paper addresses the problem of adverse pregnancy outcome in relation to
      periodontal disease. There is compelling evidence that a link exists between pre
      term low birth weight (PLBW) and periodontitis. Although 25% to 50% of PLBW
      deliveries occur without any known aetiology, there is increasing evidence that
      infection may play a significant role in pre-term delivery. A model explaining
      the plausible relationship is proposed based upon the concept of infection
      leading to a cascade of inflammatory reactions associated with pre-term labour
      and periodontal disease. Current evidence has pointed to an interest in dental
      intervention studies to control periodontal disease as one of the potential
      strategies to reduce pre-term labour. This paper reviews the potential
      association between periodontal infection and adverse pregnancy outcomes.

PMID- 15726230
TI  - Guidelines of care for cutaneous haemangiomas.
AB  - INTRODUCTION: Haemangiomas are common benign tumours of the vascular endothelium.
      They are extremely heterogenous clinically, with size, location and rate of
      proliferation having a significant effect on the risk of complications. MATERIALS
      AND METHODS: The available evidence in the literature was evaluated using the
      grading system currently employed by the Ministry of Health, Singapore. RESULTS:
      An uncomplicated haemangioma can be observed for spontaneous involution. However,
      some haemangiomas may be life- or function-threatening, or have associated
      structural anomalies. Corticosteroids may be used topically, intralesionally or
      systematically. Interferon alpha, vincristine and cyclophosphamide are
      therapeutic options for complicated haemangiomas which do not respond to
      corticosteroids. Vascular-specific pulse dye laser therapy may be considered for
      superficial haemangiomas, ulcerated haemangiomas or post-involution sequelae like
      telangiectasia. The mainstay of therapy for ulcerated haemangiomas is good local
      wound care, analgesics and treatment of secondary infection. A periorbital
      haemangioma that obstructs the visual axis or exerts pressure on the globe is an
      ocular emergency. Systemic corticosteroids and patching of the unaffected eye
      should be considered. CONCLUSIONS: Medical practitioners should be aware of
      available therapeutic options for life- or function-threatening haemangiomas.
      Treatment must be individualised and referral to the relevant specialist should
      be considered in patients with complicated haemangiomas.

PMID- 15726231
TI  - Clinical usefulness of endoscopic ultrasonography with or without fine needle
      aspiration in the diagnosis and staging of pancreatic carcinoma.
AB  - INTRODUCTION: The aims of this study was to show the accuracy and clinical
      usefulness of endoscopic ultrasonography (EUS) with EUS-guided fine needle
      aspiration (FNA) in the diagnosis and staging of pancreatic cancer not obvious in
      computed tomographic (CT) scan abdomen imaging. MATERIALS AND METHODS: Five male
      patients were evaluated; 4 presented with obstructive jaundice and 1 had
      unexplained loss of weight. The mean age was 66 years (range, 40 to 77). All had
      CT scan abdomen imaging which did not show any obvious pancreatic tumour. EUS
      with FNA was done for all cases when indicated. Surgical findings, if any, were
      obtained and compared to EUS findings. RESULTS: EUS easily detected the
      pancreatic tumour in all 5 cases. The tumour sizes detected ranged from 27 to 40
      mm in diameter. These corresponded fairly accurately with that of surgical
      findings for all 3 who had surgery. EUS reported 3 cases with pathological lymph
      node involvement. All 5 cases were confirmed by FNA or surgery. EUS was also
      accurate in 4 cases, which reported the absence of portal vein or superior
      mesenteric vein invasion. Surgical documentation could not verify the fifth case.
      There were no complications at all from the EUS with/without FNA. CONCLUSION:
      This case series showed that EUS with/without FNA appears to be useful and safe
      in diagnosing and staging pancreatic head tumours not detectable by CT scanning.

PMID- 15726232
TI  - Rapid cystic development in relation with an impacted lower third molar: a case
      report.
AB  - Cystic changes can arise in relation with unerupted lower third molars. This case
      report describes a large odontogenic keratocyst (OKC) which developed rapidly and
      aggressively over a short period of 2 years and presented with acute symptoms.
      The development of a large OKC over the mandible is evidenced by radiographs
      taken 2 years apart. The OKC was enucleated and the residual cavity was treated
      with Carnoy's solution and packed with bismuth iodoform paraffin paste dressing.
      The impacted third molar and second molar associated with the lesion were also
      extracted. This case illustrates how rapidly a cyst can develop in association
      with a previously asymptomatic, unerupted tooth and how quickly a radiographic
      diagnosis can become out of date. As such, the authors recommend the use of
      repeated radiographs for monitoring unerupted teeth at a tighter time frame of 6
      to 12 months.

PMID- 15726233
TI  - Legal issues in the treatment of a violent manic patient in a non-gazetted
      setting: a case report.
AB  - INTRODUCTION: Psychiatrists in non-gazetted treatment settings, like psychiatric
      wards in restructured general hospitals and private hospitals, face a major
      problem when psychiatric patients who require admission are either not competent
      or refuse to consent to admission and treatment, although they are clearly in
      need of such inpatient management. Admission to the state mental hospital is
      often refused by their relatives for a number of reasons, like the stigma
      attached to admission to such a hospital, and the fear that future employment
      prospects might be affected. CLINICAL PICTURE: Mr X, a manic, violent patient,
      had no insight into his disorder and refused admission and treatment for his
      manic episode. He was the head of a large corporation, and his relatives were
      apprehensive he would make decisions that could jeopardize the company.
      TREATMENT: He refused oral medication, could not tolerate parenteral haloperidol
      and had lithium nephrotoxicity. Inpatient electroconvulsive therapy had to be
      administered, after which he responded satisfactorily. CONCLUSION: The legal
      implications in this case, like consent for treatment and admission, and ethical
      issues, are discussed.

PMID- 15726234
TI  - Rapid Identification of pathogenic rapidly growing mycobacteria by PCR
      restriction endonuclease analysis.
AB  - INTRODUCTION: The accuracy and practicality of PCR-restriction endonuclease
      analysis (PRA) for rapid identification of pathogenic rapidly growing
      mycobacteria (RGM) isolates were evaluated. MATERIALS AND METHOD: PRA
      identification using an amplified 439-bp segment (amplicon) of the 65-kDa heat
      shock protein gene was compared to identification by conventional methods, for 39
      clinically significant RGM isolates. RESULTS: The accuracy of PRA in the
      identification of RGM isolates was comparable to that of conventional methods.
      Moreover, PRA was able to identify RGM faster, within 2 to 3 working days
      compared to conventional methods which require 2 to 4 weeks to perform and
      complete different tests. CONCLUSION: PRA methodology could be easily
      incorporated into the clinical laboratory setting. This would be beneficial for
      the management of patients with infections due to pathogenic RGM.

PMID- 15726236
TI  - Hypovitaminosis D, impaired bone turnover and low bone mass are common in
      patients with peripheral arterial disease.
AB  - Hypovitaminosis D is common in patients with peripheral arterial disease (PAD).
      Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain
      and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95
      out of 297 patients with angiographically confirmed PAD stages II (pain in the
      calves and/or thighs only during exercise) or IV (history of, or presence of
      local ulcers) and compared them with 44 matched healthy controls regarding their
      medical history, bone density measurements of the femoral neck and calcaneal bone
      ultrasound. Bone pain, myalgias and mobility restriction as well as routine
      laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid
      hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and
      analysed. 25(OH)D was significantly lower in PAD IV patients (9.6+/-4.6 ng/ml,
      P<0.0001) as compared to PAD II stages and controls (19.0+/-7.6 and 19.1+/-9.1
      ng/ml), paralleled by lower serum calcium [2.24+/-0.02 mmol/l, P=0.0002 versus
      PAD II (2.36+/-0.02) and P<0.0001 versus controls (2.39+/-0.02)] and higher iPTH
      serum levels (66.3+/-3.6 pg/ml, P<0.0001) as compared to PAD II patients (45.3+/
      3.5) and healthy controls (38.5+/-2.4). Alkaline phosphatase and serum crosslaps
      values were significantly higher and age-adjusted bone density and bone
      ultrasound measurements significantly lower in PAD IV patients, who were also
      twice as likely to have bone pain and myalgias as PAD II patients. Bone
      ultrasound measurements correlated significantly with both clinical severity and
      pain as well as serological parameters of bone metabolism. Underlying PAD has a
      significant impact on bone density and metabolism as well as on bone and muscular
      pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and
      should be regularly monitored and treated for their vitamin D deficiencies.

PMID- 15726237
TI  - Predictors of compliance with a home-based exercise program added to usual
      medical care in preventing postmenopausal osteoporosis: an 18-month prospective
      study.
AB  - This prospective 18-month study was designed to assess long-term compliance with
      a program of exercise aimed to prevent osteoporosis after an educational
      intervention and to uncover determinants of compliance. A total of 135
      postmenopausal women were recruited by flyers or instructed by their physicians
      to participate in an educational session added to usual medical care. After a
      baseline visit and dual-energy X-ray absorptiometry, volunteers participated in a
      1-day educational session consisting of a lecture and discussion on guidelines
      for appropriate physical activity and training in a home-based exercise program
      taught by a physical therapist. Scheduled follow-up visits were 1, 6, and 18
      months after the educational session. Compliance with the exercise program was
      defined as an exercise practice rate 50% or greater than the prescribed training.
      The 18-month compliance rate was 17.8% (24/135). The main reason for withdrawal
      from the program was lack of motivation. Two variables predicted compliance:
      contraindication for hormone replacement therapy (odds ratio [OR] = 0.13; 95%
      confidence interval [95% CI], 0.04 to 0.46) and general physical function scores
      from an SF-36 questionnaire (OR=1.26; 95% CI, 1.03 to 1.5). To a lesser extent,
      osteoporosis risk, defined as a femoral T-score < or =-2.5, predicted compliance
      (OR=0.34; 95% CI, 0.10 to 1.16). Despite the addition of an educational session
      to usual medical care to inform participants about the benefits of exercise, only
      a minority of postmenopausal women adhered to a home-based exercise program after
      18 months.

PMID- 15726235
TI  - Evidence-based guidelines for the treatment of postmenopausal osteoporosis: a
      consensus document of the Belgian Bone Club.

PMID- 15726238
TI  - Clinical and panoramic predictors of femur bone mineral density.
AB  - Dentists are a potentially valuable resource for initial patient screening for
      signs of osteoporosis, as individuals with osteoporosis have altered architecture
      of the inferior border of the mandible as seen on panoramic radiographs. Our aim
      was to evaluate the efficacy of combining clinical and dental panoramic
      radiographic risk factors for identifying individuals with low femoral bone mass.
      Bone mineral density was measured at the femoral neck and classified as normal,
      osteopenic or osteoporotic using WHO criteria in 227 Japanese postmenopausal
      women (33-84 years). Panoramic radiographs were made of all subjects. Mandibular
      cortical shape and width was determined and trabecular features were measured in
      each ramus. Mean subject age, height, and weight were significantly different in
      the three bone-density groups (P<0.0001). A classification and regression trees
      (CART) analysis using just clinical risk factors identified 136 (87%) of the 157
      individuals with femoral osteopenia or osteoporosis. Mean mandible cortical width
      (P<0.0001), cortical index (P<0.0001) and trabecular features (P=0.02) were also
      significantly different in the three bone density groups. A CART analysis
      considering only radiographic features found 130 (83%) of the 157 individuals
      with femoral osteopenia or osteoporosis, although none of the subjects with
      osteoporosis was correctly identified. A CART analysis using both clinical and
      radiographic features found that the most useful risk factors were thickness of
      inferior border of the mandible and age. This algorithm identified 130 (83%) of
      the 157 individuals with femoral osteopenia or osteoporosis. The results of this
      study suggest that 1) clinical information is as useful as panoramic radiographic
      information for identifying subjects having low bone mass, and 2) dentists have
      sufficient clinical and radiographic information to play a useful role in
      screening for individuals with osteoporosis.

PMID- 15726240
TI  - [Perioperative evaluation of lung function].
AB  - Respiratory diseases contribute significantly to perioperative morbidity and
      mortality. Severe pulmonary complications usually emerge postoperatively. To
      minimise pulmonary risk, the perioperative evaluation of lung function is of
      major significance, allowing the identification of patient and surgery-related
      risk factors. In particular, the significance of the intraoperative assessment of
      lung function has gained in importance over the last few years. The following
      article describes the possibilities and frontiers of the perioperative assessment
      of lung function, and focuses especially on the significance of preoperative
      pulmonary function tests and the intraoperative interpretation of respiratory
      pressure, flow, and volume loops.

PMID- 15726239
TI  - [Hypoglycemia despite hyperglycemia. Is a cerebral glucose deficiency possible
      even with raised blood sugar levels?].
AB  - Hypoglycemia represents the most frequent endocrinologic emergency situation in
      prehospital patient care. As the patients are usually unconscious on arrival of
      emergency medical personnel, often the only way to establish a diagnosis is by
      determination of the blood glucose concentration. However, even normoglycemic or
      hyperglycemic levels cannot definitively exclude the diagnosis of a previous
      hypoglycemia as the cause of the acute cerebral deficiency. Therefore, and
      especially in the case of insulin-dependent diabetes mellitus, a differential
      diagnosis should be considered. We report a case of emergency treatment of a
      hypoglycemic episode in a female patient with prolonged neuroglycopenia together
      with cerebrovascular dementia and Alzheimer's disease.

PMID- 15726242
TI  - [The toxicity of ropivacaine is dose, not concentration dependent].

PMID- 15726241
TI  - [Clinical risk management. Implementation of an anonymous error registration
      system in the anesthesia department of a university hospital].
AB  - BACKGROUND: The main goal of a medical risk management system is reduction of
      treatment errors and the primary focus is patient safety. MATERIALS AND METHODS:
      A task force on risk management in anaesthesia was established in the department
      of Anaesthesiology and Intensive Care at the University Hospital Dresden with the
      aim to implement a critical incident reporting system (CIRS) followed by a
      structured analysis. The theoretical basic principles and tools for the incident
      analysis are presented. RESULTS: The task force developed a machine-readable,
      structured, anonymous questionnaire, which was implemented in clinical practice
      after a primary test period. CONCLUSIONS: Prerequisites for the implementation of
      an effective CIRS are support from the department head, anonymity, independence
      of the task force from the department head and competence of the task force to
      initiate changes and improvements. CIRS is a powerful tool to register and
      analyse critical incidents and may influence the following domains: education and
      training (human factors), medical equipment (technical factors), quality of
      working processes and departmental communication (organisational factors).

PMID- 15726243
TI  - [Pharmacological peculiarities and problems with older patients].
AB  - Because of demographic developments, the fraction of the German population over
      65 years of age in the year 2025 will have risen to 20% and will continue to rise
      so that in 2030 this number will have doubled compared to today's numbers. This
      has a huge impact on the requirements for anaesthesiologic procedures. In
      addition to the frequent multi-morbidity in this age group, physiologic changes
      also occur in the elderly which have to be taken into consideration during the
      entire perioperative management of these patients. Renal, cardiovascular and
      hepatic function are impaired in many elderly patients. A major concern in
      addition to cardiovascular and operative complications is the postoperative
      cognitive dysfunction (POCD), not only because of its implications for the
      patient but also because of economical consequences. Regional anaesthesia has
      some benefits when compared to general anaesthesia as it leads to a reduction in
      thromboembolic and respiratory complications.

PMID- 15726245
TI  - Model for DNA hairpin denaturation.
AB  - We investigate the thermal denaturation of DNA hairpins using molecular dynamics
      simulations of a simple model describing the molecule at a scale of a nucleotide.
      The model allows us to analyze the different interacting features that determine
      how an hairpin opens, such as therole of the loop and the properties intrinsic to
      the stem.

PMID- 15726244
TI  - [Extended hemodynamic monitoring using transpulmonary thermodilution Influence of
      various factors on the accuracy of the estimation of intrathoracic blood volume
      and extravascular lung water in critically ill patients].
AB  - BACKGROUND: The transpulmonary thermal-dye dilution (TDD) is the clinical gold
      standard for measurement of intrathoracic blood volume (ITBV) and extravascular
      lung water (EVLW). Recently, experimental and clinical studies found that ITBV
      and EVLW can be derived reliably by single transpulmonary thermodilution (TD),
      however, dependency from various factors of lung function has been discussed.
      PATIENTS AND METHODS: We retrospectively analyzed data from 174 critically ill
      patients who had undergone hemodynamic monitoring by TDD. We calculated the
      differences of simultaneous TD and TDD determined by ITBV or EVLW measurements.
      Bias and standard deviations (SD) were calculated and extended Bland-Altman
      regression analyses were performed. Association of the differences and the
      potential confounders gender, age, PEEP, p(a)O(2)/F(I)O(2) ratio and the
      corresponding TDD measurement were analyzed by multiple linear regression and
      LOWESS regression. RESULTS: Overall results (bias+/-SD) were 1+/-58 ml/m(2) for
      ITBV and 0.0+/-1.4 ml/kg bw for EVLW, but TD overestimated TDD results in
      patients with higher ITBV and underestimated those for lower ITBV values. The
      deviations were small, and the dependence of ITBV could be explained completely
      by dependence on PEEP and age. However, low values of EVLW are overestimated by
      TD. CONCLUSION: Single transpulmonary thermodilution for estimation of ITBV or
      EVLW is reliable in patients with severe lung injury for normal and higher
      values.

PMID- 15726246
TI  - Global symmetry breaking in the nonconserved order parameter system during phase
      ordering.
AB  - We study global symmetry breaking in the 2D system of scalar nonconserved order
      parameter following a quench to zero temperature. We show that the instant of
      time when the symmetry is broken and the final morphology is chosen corresponds
      to the saturation of the order parameter inside the domains. There are three
      possible final morphologies: the positive and negative order parameter final
      morphology, and the state of the coexisting positive and negative order parameter
      subsystems with a flat interface between them. We find also that each type of the
      final morphology constitutes about 1/3 of all cases, what agrees with the results
      obtained recently by Spirin et al. [Phys. Rev. E 65, 016119 (2001)]. Our results
      are pertinent for the two dimensional systems, but we suspect that there is also
      a way to apply similar arguments for the three dimensional ones.

PMID- 15726247
TI  - No evidence of increased oxidative degradation of urate to allantoin in the CSF
      and serum of patients with multiple sclerosis.

PMID- 15726248
TI  - Beware of neuro-syphilis.

PMID- 15726249
TI  - Volume cerebral blood flow reduction in pre-clinical stage of Alzheimer disease:
      evidence from an ultrasonographic study.
AB  - The association of decreased cerebral blood flow with the development of
      Alzheimer's disease (AD) has been a recent target of interest. By using
      neuroimaging techniques, growing attention has been devoted to the identification
      of preclinical AD. In this study, color duplex sonography of cervical arteries
      was used to measure mean cerebral blood flow (CBF) on 55 amnestic Mild Cognitive
      Impairment (MCI) patients. Two years after enrollment, excluding patients who
      progressed to dementia other than AD, two subgroups were identified, patients who
      developed AD (MCI converters) and patients with preserved cognitive and
      functional level (MCI non-converters). Examining the mean difference of CBF
      measured at baseline in the two subgroups obtained, a significant difference was
      noticed (MCI converters 539.3 +/- 114.3 vs MCI non converters 636.0 +/- 143.9, p
      < 0.05). MCI patients with CBF higher than median value (558 ml/min) had lower
      risk of developing AD (specificity 72.2%, sensitivity 68.4%) within a two year
      follow-up. Ultrasonography of the cervical arteries is a simple, non invasive and
      widespread technique useful in detecting CBF decline during the MCI stage, thus
      identifying patients who later will convert to AD.

PMID- 15726250
TI  - A genome wide linkage disequilibrium screen in Parkinson's disease.
AB  - Whole genome screening is increasingly used to identify genetic risk factors for
      complex diseases. In this study, a genome wide linkage disequilibrium (LD) screen
      was performed in a cohort of Parkinson's disease (PD) patients from the UK (n =
      195) using pooled DNA to facilitate efficient genotyping of 5546 microsatellite
      markers. Allele frequencies were compared with those found in 2 previously typed
      disease free control populations, and the most interesting markers were selected
      for multiple repeat testing among the 3 pools. Markers were then individually
      genotyped in our original PD cohort and one of the original control groups, and
      independently in a second cohort of UK PD patients (n = 179), and additional
      controls. Using this 2-stage approach, we have been unable to find evidence for
      consistent association of any markers with sporadic PD. Subgroup analysis of the
      most promising marker shows some evidence that microsatellite marker D1S2886 is
      associated with familial forms of the disease.

PMID- 15726251
TI  - Working memory and FDG-PET dissociate early and late onset Alzheimer disease
      patients.
AB  - The aims of this study were to determine the influence of the onset of
      Alzheimer's disease (AD) on 1) memory and cerebral glucose metabolism, 2) the
      relationships between cognitive performance and cerebral glucose metabolism.
      Brain metabolism was measured by 18FDG-PET in 12 early onset AD patients (age <
      65 years) and 26 late onset ones (> 65), with comparable mean MMSE scores.
      Working memory, semantic memory and episodic memory were assessed. Cognitivo
      metabolic correlations (CMC) and complementary interregional correlations were
      performed in order to identify specific neurocognitive processes within each
      group. Both AD groups performed poorly on all tasks, except digit span in the
      late onset group. The early onset group performed more poorly than the late onset
      one on both the digit span and Brown-Peterson Paradigm (BPP) tasks. Temporo
      parietal hypometabolism was found in both groups, the left hemisphere being more
      affected than the right, especially in the early onset patients, who also showed
      specific left frontal hypometabolism. For the BPP task, the CMC principally
      involved left frontal areas in the early onset group, and the cerebellum in the
      late onset one. For the digit span task, they involved cerebellar and occipital
      regions in the latter. Regarding the digit span, the occipital and cerebellar
      involvement may have reflected an effective compensatory mechanism in the late
      onset patients, while high left supramarginal gyrus hypometabolism in the early
      onset patients may have explained their failure in this task. In the BPP task,
      the lower performance of the early onset group may have been due to a frontal
      lobe dysfunction, as suggested by 1) the hypometabolism of this region, 2) the
      CMC results, 3) the interregional correlations, which indicated greater
      disruption of the antero- posterior loop.

PMID- 15726252
TI  - Diagnostic value of muscle MRI in differentiating LGMD2I from other LGMDs.
AB  - Mutations in the fukutin-related protein (FKRP) have recently been demonstrated
      to cause limb girdle muscular dystrophy type 2I (LGMD2I), one of the most common
      forms of the autosomal recessive LGMDs in Europe. We performed a systematic
      clinical and muscle MRI assessment in 6 LGMD2I patients and compared these
      findings with those of 14 patients with genetically confirmed diagnosis of other
      forms of autosomal recessive LGMDs or dystrophinopathies. All LGMD2I patients had
      a characteristic clinical phenotype with predominant weakness of hip flexion and
      adduction, knee flexion and ankle dorsiflexion. These findings were also mirrored
      on MRI of the lower extremities which demonstrated marked signal changes in the
      adductor muscles, the posterior thigh and posterior calf muscles. This
      characteristic clinical and MRI phenotype was also seen in LGMD2A. However, in
      LGMD2A there was a selective involvement of the medial gastrocnemius and soleus
      muscle in the lower legs which was not seen in LGMD2I. The pattern in LGMD2A and
      LGMD2I were clearly different from the one seen in alpha-sarcoglycanopathy and
      dystrophinopathy type Becker which showed marked signal abnormalities in the
      anterior thigh muscles. Our results indicate that muscular MRI is a powerful tool
      for differentiating LGMD2I from other forms of autosomal recessive LGMDs and
      dystrophinopathies.

PMID- 15726254
TI  - Intracranial granulocytic sarcoma (chloroma) may mimic a subdural hematoma.

PMID- 15726253
TI  - High specificity of myositis specific autoantibodies for myositis compared with
      other neuromuscular disorders.
AB  - Myositis specific autoantibodies (MSAs) are proven to be specific for myositis
      compared with other inflammatory connective tissue diseases. Their specificity
      compared, however, with other neuromuscular disorders, which are included in the
      differential diagnosis of patients in whom the diagnosis myositis is under
      consideration, is unknown. We prospectively screened sera from 107 patients with
      various neuromuscular disorders for the most common MSAs and compared the results
      with the findings in a group of 97 myositis patients, published previously.
      Special attention was paid to patients with facioscapulohumeral muscular
      dystrophy (FSHD), an autosomal dominant muscle disease with marked inflammation
      in skeletal muscle tissue. Only one patient in the neuromuscular disorders group
      tested positive for an MSA, compared with 41 in the myositis group, resulting in
      a specificity of 99%. None of the FSHD patients tested positive. We conclude that
      the tested MSAs are highly specific for myositis and that they are not merely
      associated with muscle inflammation.

PMID- 15726255
TI  - Sensorimotor integration in patients with parkinsonian type multisystem atrophy.
AB  - Sensorimotor integration is an essential feature of the central nervous system
      that contributes to the accurate performance of motor tasks. Some patients with
      multiple system atrophy with parkinsonian features (MSAp) exhibit clinical signs
      compatible with an abnormal central nervous system excitability to somatosensory
      inputs, such as action myoclonus or enhanced cutaneo-muscular reflexes. To
      investigate further the site where such dysfunction in sensorimotor integration
      takes place, we examined the inhibitory effects of a cutaneous afferent volley at
      two different levels of the motor system in 10 MSAp patients and in 10 age
      matched healthy volunteers. Electrical digital nerve stimuli were given as the
      conditioning stimulus for the motor evoked potentials (MEP) elicited by
      transcranial magnetic stimulation in hand muscles, and for the blink reflex
      responses obtained in the orbicularis oculi muscles by supraorbital nerve
      stimulation. Intervals for the conditioning were 20 to 50 ms for the MEP and 90
      to 110 ms for the blink reflex. The MEP was significantly inhibited in test
      trials in healthy volunteers, reaching a mean of 32% of the baseline values at
      the ISI of 35 ms. Significant inhibition occurred also in the blink reflex, in
      which the R2 response was a mean of 12% of baseline values at the ISI of 100 ms.
      The inhibitory effects were abnormally reduced in 8 patients on the MEP, and in 7
      patients on the blink reflex. There were significant group differences between
      patients and control subjects in the size of the conditioned MEP and blink
      reflex. These results suggest that sensorimotor integration is abnormal in
      patients with MSAp in at least two central nervous system sites: the sensorimotor
      cortex, and the brainstem reticular formation.

PMID- 15726256
TI  - Retrospective analysis of variables favouring good surgical outcome in posterior
      epilepsies.
AB  - AIM: to determine variables favouring good surgical outcome in posterior
      epilepsies. METHODS: Fourteen patients submitted to epilepsy surgery were
      included in the study. The epileptogenic zone was located in temporo-parieto
      occipital areas as assessed by both invasive and non-invasive pre-surgical
      evaluation. Several variables (age at first seizure; age at surgery; disease
      duration; type, frequency and clinical semiology of seizures; presence of lesion;
      scalp ictal and interictal EEG; localization and extension of epileptogenic zone;
      completeness of surgical resection) were compared (Fisher's exact test) with
      freedom from seizures to determine whether surgical outcome (Engel's
      classification) could be related to any of them. RESULTS: Seven patients were
      seizure free (Ia) and very satisfying results were obtained for 3 patients (2 Ib,
      1 Ic). New post-surgical visual deficits occurred only in 3 patients. Surgical
      outcome was related significantly to two variables: scalp ictal EEG (focal versus
      non-focal; p: 0.014) and completeness of surgical resection of epileptogenic zone
      (p: 0.0023). A significant trend towards a better outcome for focal interictal
      intracranial activity versus a non-focal one (p: 0.07) was found. CONCLUSIONS:
      The correlation between completeness of epileptogenic zone resection and surgical
      outcome suggests that a presurgical protocol, allowing a precise definition of
      the area of resection, could help in obtaining more satisfying results in
      posterior epilepsies.

PMID- 15726257
TI  - Motor and non motor effects during intraoperative subthalamic stimulation for
      Parkinson's disease.
AB  - Spatial distribution of the clinical effects induced by deep brain stimulation
      during the intraoperative investigation of the subthalamic nucleus (STN) for
      Parkinson's disease (PD) was analysed in 17 patients under local anesthesia. The
      stimulation parameters were 130 hertz, 100 micros, and voltage ranged from 0.05
      to 5 volts. Optimal motor response was assessed as the total and lasting
      disappearance of wrist rigidity on the side opposite to stimulation. Among the
      adverse effects induced by stimulation, special attention was given to frequently
      observed autonomic effects (AE). Full motor response was achieved in 49.2% of the
      301 points evaluated,with a mean voltage (MV) of 0.94 volts; paresthesiae
      occurred in 6.6% (MV: 2 volts), dystonia in 10.6% (MV: 3.4 volts), autonomic
      effects in 19.6% (MV: 3.1 volts) and oculomotor effects in 31.6% (MV: 3 volts).
      The motor target was located in the posterodorsal part of the nucleus and the
      optimal point for motor response was close to the superior limit of the nucleus.
      Whereas other adverse effects occurred relatively far from the motor target, AE
      occurred with statistic significance near this point. Their neural substrates,
      such as limbic system and their relationship with postoperative behavioral
      disorders, are discussed.

PMID- 15726258
TI  - Improvement of cardiovascular autonomic dysfunction following anti-copper therapy
      in Wilson's disease.

PMID- 15726259
TI  - Symptomatic focal mononeuropathies in diabetic patients: increased or not?
AB  - The aim of this study was to investigate whether symptomatic mononeuropathies are
      more frequent in diabetic patients without symptoms of acute or subacute
      polyneuropathy than in the general population.For this purpose, six hundred and
      forty two consecutive outpatients with various acute symptomatic mononeuropathies
      (radial, ulnar or peroneal neuropathy, Bell's palsy or carpal tunnel syndrome)
      without symptoms of acute or subacute polyneuropathy were studied. The results
      showed that in 522 patients with symptomatic carpal tunnel syndrome (CTS) and in
      38 patients with Bell's palsy, the rate of diabetes was 7.7% and 10.5%,
      respectively. These rates do not differ significantly from the anticipated
      frequency of diabetes in the general population. On the other hand, in 18
      patients with radial neuropathy at (or distally to) the spiral groove, in 41
      patients with ulnar neuropathy and in 23 patients with peroneal neuropathy at the
      fibular head, the respective rates were 27.8%, 12.2 % and 30.4%. These rates are
      significantly higher than those anticipated according to the frequency of
      diabetes in the general population. The findings of the present study indicate
      that only focal limb neuropathies due to acute external compression are more
      frequent in diabetic patients.

PMID- 15726260
TI  - Morphometry demonstrates loss of cortical thickness in cerebral microangiopathy.
AB  - OBJECTIVE: To evaluate the role of MR morphometry in the characterization of
      cerebral microangiopathy (CMA) in relation to clinical and neuropsychological
      impairment. SUBJECTS AND METHODS: 3D MR images of 27 patients and 27 age-matched
      controls were morphometrically analysed for regional thickness. The normalized
      values were related to the patients' clinical and neuropsychological scores. The
      patients were categorised according to the amount of structural MR signal
      changes. A ventricle index reflecting internal atrophy was related to MR
      morphology and cortical thickness as an indicator for external atrophy. RESULTS:
      Cortical thickness was significantly reduced in the patients group (3.03 mm +/-
      0.26 vs. 3.22 mm +/-0.13 in controls, p=0.001). The severest loss of cortical
      thickness occurred in severe CMA. Internal and external atrophy evolved in
      parallel and both showed a significant relationship with structural MR
      abnormalities (p<0.05; r=-0.7; r=0.67; r=-0.74, respectively). Neuropsychological
      performance correlated strongly with the loss of cortical thickness. CONCLUSIONS:
      Cortical thickness was identified as the most sensitive parameter to characterize
      CMA. A strong correlation was found of morphometric parameters to the severity of
      CMA based on a score derived from T2-weighted MRI. The degree of cortical atrophy
      was directly related to the degree of neuropsychological impairment. Our findings
      suggest that the cortical thickness is a valid marker in the structural and
      clinical characterization of CMA.

PMID- 15726261
TI  - The prevalence of multiple sclerosis in the north-west Italian province of Genoa.
AB  - The objective of this study was to assess the prevalence of multiple sclerosis
      (MS), calculated as point prevalence on 31 December 1997, in the province of
      Genoa, North-western Italy. METHODS: The province of Genoa is located in North
      western Italy, an area of 1,835 km(2). On the point prevalence day the population
      consisted of 913,218 inhabitants. MS cases were identified by analysing archives
      of the hospitals with neurological or rehabilitation wards, neurologists serving
      the community, files of local chapters of the Italian MS society, all requests
      for oligoclonal bands analysis on CSF in the studied area. Patients included in
      the study were MS cases diagnosed before 31 December 1997 according to the Poser
      criteria resident in the province under study. RESULTS: A total of 857 subjects
      were alive and residing in the province of Genoa on the prevalence day. The
      overall crude prevalence rate was 94 per 100,000 (95% CI 88-100); 291 were males
      (34%) with a crude prevalence of 67 per 100,000 (95 % CI 60-76) and 566 were
      females (66%) with a prevalence of 118 per 100,000 (95% CI 108-128). The
      female/male ratio was 1.9. When age and sex were adjusted to the Italian standard
      population of 1991 prevalence was 85 per 100,000. Five hundred and thirty two out
      of the 857 patients agreed to be interviewed. The interviewed sample was
      representative of the prevalence sample: sex and gender distributions were
      identical in the two samples. The overall mean age was 48 (+/-13) years (48 +/-12
      years in males; 48+/-14 years in females). Mean disease duration was 15 (+/-10)
      years for males and 16 (+/-11) years for females. Two hundred and ninety one (55
      %) subjects had a relapsing remitting (RR) clinical course, 150 (28%) were
      secondary progressive (SP) and 91 (17%) were primary progressive (PP). Mean EDSS
      score was 5 (+/- 2; median 5). The mean age at time of onset was 33 (+/-10) years
      for males and 32 (+/- 11) years for females. The disease onset was
      monosymptomatic in 76% (n=407) patients and polysymptomatic in 24% (n=125). The
      mean length of time between clinical onset and diagnosis was 5 (+/- 6) years.
      CONCLUSION: We confirmed that the province of Genoa is a very high risk area for
      MS. We found a high rate of patients with a PP course; also the proportion of
      patients with high disability scores is greater compared to previous studies.

PMID- 15726262
TI  - Corticonuclear innervation to facial muscles in normal controls and in patients
      with central facial paresis.
AB  - Recently it has been proposed that corticobulbar innervation of the lower facial
      muscles is bilateral, that is from both right and left sides of the motor cortex.
      The objectives of this study were, i) to evaluate the corticonuclear descending
      fibers to the perioral muscles and, ii) to determine how central facial palsy
      (CFP) occurs and often recovers rapidly following a stroke. Eighteen healthy
      volunteers and 28 patients with a previous history of a stroke and CFP (mean
      ages: 51 and 61 years) were investigated by TMS (transcranial magnetic
      stimulation) with a figure of eight coil. Intracranial facial nerve and cortical
      motor evoked potentials (MEPs) were recorded from the perioral muscles. The
      periorbital MEPs were also studied. The absence of MEPs in both perioral muscles
      with TMS of the affected hemisphere was the most obvious abnormality. Also,
      central conduction time was significantly prolonged in the remaining patients.
      The mean amplitude of the affected hemisphere MEPs was diminished. The amplitudes
      of the unaffected hemisphere MEPs recorded from the intact side were enhanced
      especially in the first week following the stroke. During TMS, only the blink
      reflexes were elicited from the periorbital muscles due to stimulus spreading to
      trigeminal afferent nerve fibers. It is concluded that perioral muscles are
      innervated by the corticobulbar tract bilaterally. CFP caused by a stroke is
      generally incomplete and mild because of the ipsilateral cortical and multiple
      innervations out of the infarction area, and recovers fast through cortical
      reorganisation.

PMID- 15726263
TI  - Soluble Telencephalin in the serum of children after febrile seizures.

PMID- 15726265
TI  - Atypical reversible eclamptic encephalopathy: utility of diffusion weighted MRI
      and ADC values.

PMID- 15726264
TI  - Genetic analysis of BDNF and TrkB gene polymorphisms in Alzheimer's disease.
AB  - According to previous biochemical and genetic findings, brain-derived
      neurotrophic factor (BDNF), via activation of its tyrosine kinase receptor B
      (TrkB), is considered as a plausible candidate for contributing to Alzheimer's
      disease (AD). To examine the genetic association of BDNF and TrkB genes with AD,
      we genotyped multiple single nucleotide polymorphisms (SNPs) within these genes
      among 375 Finnish AD patients and 460 control subjects. Single locus and multi
      loci haplotype association analyses of BDNF and TrkB gene SNPs did not reveal
      significant differences between unstratified AD and control groups. In the case
      of BDNF SNPs, different allele and haplotype frequencies were observed when 160
      sporadic AD cases were compared with 460 control subjects. However, these
      differences did not remain statistically significant after multiple corrections.
      We conclude that BDNF and TrkB genes are not contributing significant risk effect
      among Finnish AD patients.

PMID- 15726266
TI  - Ischemic stroke in patients with glioblastoma multiforme.

PMID- 15726268
TI  - Surgical treatment of nonbacterial thrombotic endocarditis presenting with
      stroke.
AB  - BACKGROUND: Necropsy studies have shown that nonbacterial thrombotic endocarditis
      (NBTE) may be associated with cerebral infarctions and antemortem diagnosis is
      now possible. However, the best treatment for patients with NBTE presenting with
      stroke is not known. We describe three patients presenting with an acute embolic
      stroke secondary to large,mobile vegetations detected by transthoracic (one case)
      or transesophageal echocardiography (two cases). All patients underwent surgery
      for removal of the vegetations to prevent recurrent embolic events; valve
      replacement was necessary in two cases. The sterile nature of the vegetations was
      confirmed by pathological examination and negative stains and cultures of the
      surgical samples. A previously unrecognized hypercoagulable condition was
      diagnosed in all patients (antiphospholipid antibody syndrome in two cases and
      disseminated adenocarcinoma in one case). CONCLUSION: NBTE should be considered
      among the possible causes of embolic stroke even in the absence of history of
      cancer, hypercoagulability, or previous embolic manifestations. If NBTE is
      diagnosed, the possibility of underlying thrombophilia should be thoroughly
      investigated. Valvular surgery represents a valuable therapeutic alternative in
      patients with large mobile vegetations, valvular dysfunction or recurrent embolic
      events despite anticoagulation.

PMID- 15726270
TI  - Congenital afibrinogenemia complicated by spontaneous cerebral hemorrhage and
      unusually quick resorption.

PMID- 15726269
TI  - Follow-up of advanced diabetic neuropathy: useful variables and possible
      pitfalls.
AB  - BACKGROUND: The course of advanced diabetic neuropathy (DN) is largely unknown.
      AIM: To find variables allowing the follow-up of late stages of DN. METHODS:
      Thirty diabetic patients with DN were observed. Patients were examined at
      intervals of 6 months over a period of 2 years. The compound muscle action
      potentials (CMAPs) were recorded in extensor digitorum brevis (EDB) and flexor
      hallucis brevis (FHB) muscles. Clinical severity of DN, nerve conduction studies
      (NCS), quantitative sensory testing (QST) and heart rate variability (HRV) were
      evaluated. The data were compared with age- and sex-matched controls. RESULTS:
      All measures were sensitive to the detection of DN. Significant deterioration
      during follow-up was exclusively found in CMAP analysis of the EDB (p<0.05) and
      FHB muscles (p<0.03). NCS, QST and HRV remained unchanged within the 2 years of
      observation. Coincidental changes might occur, if only two time points are chosen
      for followup. CONCLUSION: Our results indicate that ongoing axonopathy
      predominates in advanced DN. Repeated testing helps to minimize the impact of
      coincidental or chance changes in DN follow-up studies.

PMID- 15726267
TI  - Genes and outcome after aneurysmal subarachnoid haemorrhage.
AB  - OBJECTIVES: Initial and secondary ischaemia are important determinants of outcome
      after subarachnoid haemorrhage (SAH). Cerebral ischaemia is a potent stimulus for
      expression of genes that may influence recovery.We investigated whether
      functional polymorphisms in the apolipoprotein E (APOE), insulin-like growth
      factor-1 (IGF-1), tumor necrosis factor-A (TNF-A), interleukin-1A (IL-1A),
      interleukin-1B (IL-1B), and interleukin-6 (IL-6) genes are related with outcome
      after aneurysmal SAH. METHODS: Genotyping of the polymorphisms was performed in a
      consecutive series of 167 patients with aneurysmal SAH. The risk of a poor
      outcome was analysed with logistic regression with adjustment for prognostic
      factors for outcome after SAH, using the homozygotes for the wild type alleles as
      a reference. RESULTS: Patients carrying any IGF-1 non-wild type allele had a
      lower risk of a poor outcome (OR 0.4, 95% CI 0.2-1.0), while carriers of the TNF
      A non-wild type allele had a higher risk (OR 2.3, 95% CI 1.0-5.4). We could not
      demonstrate an association with outcome for APOE (APOE epsilon4 OR 0.4, 95% CI
      0.1-1.2; APOE epsilon2 OR 0.7, 95% CI 0.2-2.4), IL-1A (OR 1.8, 95% CI 0.8-4.0),
      IL-1B (OR 0.7, 95% CI 0.3-1.5) and IL-6 (OR 0.7, 95% CI 0.3-1.8) polymorphisms.
      CONCLUSIONS: Variation in some genes that are expressed after cerebral ischaemia
      may partly explain the large differences in outcome between patients with
      aneurysmal SAH. SAH patients homozygote for the IGF-1 wild type allele or
      carriers of the TNF-A non-wild type allele have a higher risk of poor outcome.
      Additional studies in other populations are needed to assess the generalisability
      of our results.

PMID- 15726271
TI  - Interhemispheric subdural haematoma from ruptured aneurysm: a case report.

PMID- 15726272
TI  - Repetitive magnetic stimulation: a novel therapeutic approach for myofascial pain
      syndrome.
AB  - The aim of this study was to evaluate the short, medium and long-term effects of
      peripheral repetitive magnetic stimulation (rMS) on myofascial pain compared with
      transcutaneous electrical nerve stimulation (TENS).Fifty-three subjects with
      myofascial trigger points (TPs) at the level of the superior trapezius muscle
      were allocated randomly to three groups. The first group (n=17) was treated with
      rMS, the second (n=18) with TENS and the third (n=18) received a placebo
      treatment. Each treatment consisted of ten daily 20-minute sessions. Patients
      were evaluated before and immediately following treatment, and at one and three
      months after the end of treatment. Outcome measures were: the "neck pain and
      disability visual analogue scale" (NPDVAS), an algometric evaluation of pain, an
      evaluation of the TP characteristics, and the range of cervical bending and
      rotation contralateral to the affected trapezius muscle. At the end of treatment,
      the rMS group showed a significant improvement in the NPDVAS, algometry, TP
      characteristics, and cervical contralateral rotation. This improvement also
      persisted at one and three months post-therapy. After treatment, the TENS group
      showed significant improvement in the same outcome measures except for algometry.
      At the one month follow-up visit, this improvement had returned to non
      significant levels in all outcome measures with the exception of NPDVAS. No
      significant effect of TENS was seen at the three-month follow-up visit. The
      placebo group showed no significant improvement in any measure. Our results
      strongly suggest that at medium and longer term intervals peripheral rMS may be
      more effective than TENS for the treatment of myofascial pain.

PMID- 15726273
TI  - Clinical characteristics of elderly patients with a cautious gait of unknown
      origin.
AB  - OBJECTIVE: To evaluate and systematically characterize a group of older adults
      with disturbed gait of unknown origin. DESIGN: Cross-sectional study. SETTING:
      Outpatient clinic in a movement disorders unit. PARTICIPANTS: Twenty-five
      patients (mean age 78.4 years) with a disturbed gait of unknown origin were
      compared with twenty-eight age matched "healthy" controls (mean age 78.2).
      MEASUREMENT: Detailed medical history, geriatric and neurological assessments.
      RESULTS: Patients walked more slowly (P<0.0001) and with shorter strides
      (P<0.0001) compared with controls. Muscle strength was lower, and static and
      dynamic balance and gait performance were worse among the patients (P<0.0001).
      The patients also tended to be more depressed (P<0.0001),more anxious (P<0.002),
      had a greater fear of falling (P<0.0001) and had lower scores on the Mini-Mental
      State Examination (P<0.005). There was no difference in the frequency of
      cerebellar or pyramidal signs in the two groups. However, neurological testing
      revealed that extrapyramidal (P<0.0001) and frontal release signs (P<0.0001) were
      more common among the patients. Neuroradiological findings were rare among the
      patients and they did not explain the changes in gait speed or fear of falling.
      CONCLUSIONS: Older adults with a disturbed gait of unknown origin appear to share
      common characteristics. They walk more slowly than "healthy" controls with
      increased unsteadiness and with excessive fear of falling. The extrapyramidal,
      frontal lobe, and limbic systems apparently play an important role, to different
      degrees, in what can be viewed as a multisystem neurodegenerative syndrome
      clearly different from "aging."

PMID- 15726274
TI  - Treatment of restless legs syndrome with subcutaneous apomorphine in a patient
      with short bowel syndrome.

PMID- 15726275
TI  - Recurrent headache and sixth nerve palsy associated with lumbar ependymoma.

PMID- 15726276
TI  - HIV-induced chorea: evidence for basal ganglia dysregulation by SPECT.

PMID- 15726278
TI  - Subcranial approach in the surgical treatment of anterior skull base trauma.
AB  - Fractures of the anterior skull base, because of the region's anatomical
      relationships, are readily complicated by neurological damage to the brain or
      cranial nerves. This review highlights the use of a subcranial approach in the
      operative treatment of injuries of the anterior skull base and compares it to the
      more traditional neurosurgical transcranial approach. The extended anterior
      subcranial approach takes advantage of the specific features of injuries in this
      region and allows direct access to the central anterior cranial base in order to
      repair fractures, close CSF fistulae and relieve of optic nerve compression. It
      avoids extensive frontal lobe manipulation. The success of the approach in
      achieving the aims of surgery with low morbidity is reviewed.

PMID- 15726277
TI  - ERP correlates of impaired error monitoring in children with ADHD.
AB  - OBJECTIVE: The purpose of the current study was to elaborate on error monitoring
      in children with Attention Deficit Hyperactivity Disorder (ADHD) using the ERP
      methodology. METHOD: Children with ADHD executed a visual Go/No-Go task with 25
      percent No-Go trials; and a two stimulus reaction time task wherein a neutral
      warning signal (S1) was presented to inform the child to prepare for an
      imperative stimulus (S2). RESULTS: In both tasks, children with ADHD responded as
      fast as controls but made twice as many errors. In addition, they failed to
      adjust their speed of responding after making an error. Exploring the error
      related potentials revealed that the error-related negativity (ERN) was the same
      for the two groups, but that children with ADHD showed a diminished error
      positivity (Pe). CONCLUSIONS: Based on these findings, we conclude that children
      with ADHD are normal in early error monitoring processes related to error
      detection, but show abnormal response strategy adjustments and are deviant in
      later error monitoring processes associated with the subjective/emotional,
      conscious evaluation of the error.

PMID- 15726279
TI  - Huge epidural hematoma after surgery for spinal cord stimulation.
AB  - OBJECTIVE AND IMPORTANCE: Spinal epidural haematoma (SEH) following implantation
      of an epidural spinal cord electrode is a very rare complication but one that
      must not be overlooked. This case is unusual because of the almost "holocord"
      extension of the haematoma and the excellent recovery obtained by prompt surgical
      treatment. CLINICAL PRESENTATION: A 69 years old man with normal serum
      coagulation parameters was submitted to spinal cord stimulation (SCS) for chronic
      pain syndrome. After a minimal L1 laminotomy the patient developed paraplegia due
      to a large haematoma at D4-L2. INTERVENTION: Surgical removal of the entire clot
      by a D4-L2 laminectomy was performed immediately. CONCLUSION: Large epidural
      haematoma can result from SCS and this complication may be cured by appropriate
      and prompt surgery.

PMID- 15726280
TI  - Acute posttraumatic paraplegia associated with asymptomatic thoracic meningioma.
AB  - A case of a patient with acute paraparesis after compression fracture of the
      twelfth vertebra with progressive neurological deterioration is reported. The
      occurrence of clinical asymptomatic thoracic meningioma and coincidence with
      posttraumatic compression fracture of the vertebra at the same level resulting in
      acute paraparesis is extremely rare.

PMID- 15726281
TI  - Land-use systems and resilience of tropical rain forests in the Tehuantepec
      Isthmus, Mexico.
AB  - Land-cover types were analyzed for 1970, 1990 and 2000 as the bases for
      determining land-use systems and their influence on the resilience of tropical
      rain forests in the Tehuantepec Isthmus, Mexico. Deforestation (DR) and mean
      annual transformation rates were calculated from land-cover change data; thus,
      the classification of land-use change processes was determined according to their
      impact on resilience: a) Modification, including land-cover conservation and
      intensification, and b) Conversion, including disturbance and regeneration
      processes. Regeneration processes, from secondary vegetation under extensive use,
      cultivated vegetation under intensive use, and cultivated or induced vegetation
      under extensive use to mature or secondary vegetation, have high resilience
      capacity. In contrast, cattle-raising is characterized by rapid expansion, long
      lasting change, and intense damages; thus, recent disturbance processes, which
      include the conversion to cattle-raising, provoke the downfall of the traditional
      agricultural system, and nullify the capacity of resilience of tropical rain
      forest. The land-use cover change processes reveal a) the existence of four land
      use systems (forestry, extensive agriculture, extensive cattle-raising, and
      intensive uses) and b) a trend towards the replacement of agricultural and
      forestry systems by extensive cattle-raising, which was consolidated during 1990
      2000 (DR of evergreen tropical rain forest = 4.6%). Only the forestry system,
      which is not subject to deforestation, but is affected by factors such as
      selective timber, extraction, firewood collection, grazing, or human-induced
      fire, is considered to have high resilience (2 years), compared to agriculture (2
      10 years) or cattle-raising (nonresilient). It is concluded that the analysis of
      land-use systems is essential for understanding the implications of land-use
      cover dynamics on forest recovery and land degradation in tropical rain forests.

PMID- 15726282
TI  - Effects of management on understory diversity in the forest ecosystems of
      northern Spain.
AB  - Pine plantations are an alternative to marginal agriculture in many countries,
      and are often presented as an option that improves biodiversity. However, these
      plantations can have adverse environmental effects if improperly managed. To
      evaluate the effect of forest management practices on biodiversity, the
      diversity, species richness, dominance and frequency of understory woody plant
      species in different forests of the Basque Country (northern Spain) were
      compared. Plantations of exotic conifers (Pinus radiata [D.] Don) of different
      ages were compared with deciduous forests of Quercus robur L. and Fagus sylvatica
      L. The effects of different types and intensities of management were taken into
      account. The differences observed were mainly conditioned by the intensity of
      forestry management, although the response varied according to forest type and
      age. In unmanaged pine plantations, the diversity and species richness of the
      understory increased rapidly after planting (while dominance decreased), remained
      stable in the intermediate age range, and reached a maximum in plantations more
      than 25 years of age. Management practices resulted in decreased understory
      diversity and species richness, as well as greater dominance. This was more
      pronounced in younger than in older stands. Moderate management, however, favored
      a greater diversity of the understory in deciduous forests. The species
      composition of the plantations and deciduous forests were different, the latter
      having a wider range of characteristic species. Knowledge of how forestry
      practices influence biodiversity (in terms of diversity, richness, dominance, and
      species composition) may allow predictions to be made about the diversity
      achievable with different management systems.

PMID- 15726283
TI  - Predicting the thermal effects of dam removal on the Klamath River.
AB  - The Klamath River once supported large runs of anadromous salmonids. Water
      temperature associated with multiple mainstem hydropower facilities might be one
      of many factors responsible for depressing Klamath salmon stocks. We combined a
      water quantity model and a water quality model to predict how removing the series
      of dams below Upper Klamath Lake might affect water temperatures, and ultimately
      fish survival, in the spawning and rearing portions of the mainstem Klamath. We
      calibrated the water quantity and quality models and applied them for the
      hydrometeorological conditions during a 40-year postdam period. Then, we
      hypothetically removed the dams and their impoundments from the models and
      reestimated the river's water temperatures. The principal thermal effect of dam
      and reservoir removal would be to restore the timing (phase) of the river's
      seasonal thermal signature by shifting it approximately 18 days earlier in the
      year, resulting in river temperatures that more rapidly track ambient air
      temperatures. Such a shift would likely cool thermal habitat conditions for adult
      fall chinook (Oncorhynchus tshawytscha) during upstream migration and benefit
      mainstem spawning. By contrast, spring and early summer temperatures could be
      warmer without dams, potentially harming chinook rearing and outmigration in the
      mainstem. Dam removal might affect the river's thermal regime during certain
      conditions for over 200 km of the mainstem.

PMID- 15726285
TI  - Estimating and comparing the diversity of marine actinobacteria.
AB  - This paper reviews the application of species richness estimators to microbial
      diversity data and describes phylogenetic approaches to comparing microbial
      communities. The techniques are demonstrated using a community of marine
      actinobacteria. Results demonstrate that marine environments harbour massive
      actinobacterial diversity. Furthermore, these predictions are likely to be severe
      underestimates due to the use of arbitrary OTU definitions.

PMID- 15726286
TI  - Diversity of cultivable actinobacteria in geographically widespread marine
      sediments.
AB  - Reports describing actinobacteria isolated from marine environments have been
      dominated by Micromonospora, Rhodococcus and Streptomyces species. Recent culture
      independent studies have shown that marine environments contain a high diversity
      of actinobacterial species that are rarely, if at all, recovered by cultivation
      based methods. In this study, it is shown that cultivation-independent methods
      can be used to guide the application of selective isolation methods. The
      detection of marine-derived actinobacterial species that have previously only
      been reported from terrestrial habitats is highlighted. This study provides good
      evidence that the previously described low diversity of actinobacterial species
      isolated from marine environments does not reflect an actual low species
      diversity, and that the use of informed selective isolation procedures can aid in
      the isolation of members of novel taxa.

PMID- 15726287
TI  - Actinophages as indicators of actinomycete taxa in marine environments.
AB  - It is necessary to continue to screen for new metabolites and evaluate the
      potential of less known and new bacterial taxa so that new and improved compounds
      for future use against drug-resistant bacteria or for chemical modification may
      be developed. There has been considerable interest in the detection and
      identification of marine microorganisms since they have been reported to produce
      bioactive compounds ranging from antitumour to antibacterial and antiviral
      agents. In this study, an improved technique that involves the exploitation of
      marine actinophages as indicators of the marine actinomycete taxa and uses marine
      bacteriophages as tools to reduce the numbers of common marine bacteria, which
      impedes the growth of rare actinomycetes on isolation plates, has been applied.
      This technique reduced the numbers of colony forming units of unwanted bacteria
      on isolation plates and hence increased the chances of detecting novel marine
      actinomycete genera for isolation and subsequent screening for antiviral
      activity.

PMID- 15726288
TI  - Novel actinobacteria from marine sponges.
AB  - Actinobacteria exclusively within the sub-class Acidimicrobidae were shown by 16S
      rDNA community analysis to be major components of the bacterial community
      associated with two sponge species in the genus Xestospongia. Four groups of
      Actinobacteria were identified in Xestospongia spp., with three of these four
      groups being found in both Xestospongia muta from Key Largo, Florida and
      Xestospongia testudinaria from Manado, Indonesia. This suggests that these groups
      are true symbionts in these sponges and may play a common role in both the
      Pacific and Atlantic sponge species. The fourth group was found only in X.
      testudinaria and was a novel assemblage distantly related to any previously
      sequenced actinobacterial clones. The only actinobacteria that were obtained in
      initial culturing attempts were Gordonia, Micrococcus and Brachybacterium spp.,
      none of which were represented in the clone libraries. The closest cultured
      actinobacteria to all the Acidimicrobidae clones from Xestospongia spp. are
      'Microthrix parvicella' and Acidimicrobium spp. Xestospongia spp. can now be
      targeted as source material from which to culture novel Acidimicrobidae to
      investigate their potential as producers of bioactive compounds. Isolation of
      sponge-associated Acidimicrobidae will also make it possible to elucidate their
      role as sponge symbionts.

PMID- 15726289
TI  - Marine actinomycetes as a source of novel secondary metabolites.
AB  - A set of 600 actinomycetes strains which were isolated from marine sediments from
      various sites in the Pacific and Atlantic Oceans were screened for the production
      of bioactive secondary metabolites. Marine streptomycete strains were found to be
      producers of well known chemically diverse antibiotics isolated from terrestrial
      streptomycetes, as in the case of marine Micromonospora strains. New marine
      members of the rare genus Verrucosispora seem to be a promising source for novel
      bioactive secondary metabolites as shown in the case of the abyssomicin producing
      strain AB-18-032.

PMID- 15726290
TI  - Marine actinomycete diversity and natural product discovery.
AB  - Microbial natural products remain an important resource for drug discovery yet
      the microorganisms inhabiting the world's oceans have largely been overlooked in
      this regard. The recent discovery of novel secondary metabolites from
      taxonomically unique populations of marine actinomycetes suggests that these
      bacteria add an important new dimension to microbial natural product research.
      Continued efforts to characterize marine actinomycete diversity and how
      adaptations to the marine environment affect secondary metabolite production will
      create a better understanding of the potential utility of these bacteria as a
      source of useful products for biotechnology.

PMID- 15726291
TI  - Exploiting marine actinomycete biosynthetic pathways for drug discovery.
AB  - Drug discovery relies on the generation of large numbers of structurally diverse
      compounds from which a potential candidate can be identified. To this end,
      actinomycetes have often been exploited because of their ability to biosynthesize
      an impressive array of novel metabolites particularly polyketides. The genetic
      organization of polyketide synthases (PKSs) makes them readily amenable to
      manipulation, and thus re-engineering artificial or hybrid PKSs to produce
      unnatural natural products is a reality. This review highlights two approaches we
      have used to generate novel polyketides by manipulating genes responsible for
      starter unit biosynthesis in the 'Streptomyces maritimus' enterocin type II PKS.
      Our preliminary investigation into the biosynthesis of neomarinone, a rare marine
      actinomycete-derived meroterpenoid, is also presented.

PMID- 15726292
TI  - Enzyme inhibitors and other bioactive compounds from marine actinomycetes.
AB  - Several enzyme-inhibitor-producing actinomycetes were isolated from various
      samples collected from the marine environment and characterized. Most of them
      produced novel compounds that are useful in medicine and agriculture.
      Actinomycete strain no. 18, which produces antibiotics against Gram-positive
      bacteria only in the presence of seawater, was isolated from sediment sampled
      from neritic sea water and characterized. The production of antibiotics was
      observed at seawater concentrations ranging from 60 to 110% (v/v). Thus, the
      production was seawater-dependent. The production of tetrodotoxin (TTX), known
      otherwise as puffer fish toxin, was investigated in various actinomycetes
      collected from the marine environment. Of 10 isolates from various sea areas, 9
      produced TTX as judged by their retention times on high-performance liquid
      chromatography (HPLC). To our knowledge, this is the first report of
      actinomycetes from the marine environment that produce TTX.

PMID- 15726293
TI  - Marine actinobacteria: perspectives, challenges, future directions.
AB  - In this paper we evaluate the current state of research on the biology and
      biotechnology of marine actinobacteria. The topics covered include the abundance,
      diversity, novelty and biogeographic distribution of marine actinobacteria,
      ecosystem function, bioprospecting, and a new approach to the exploration of
      actinobacterial taxonomic space. An agenda for future marine actinobacterial
      research is suggested based upon consideration of the above issues.

PMID- 15726294
TI  - Reduction in normalized bone elasticity following long-term bisphosphonate
      treatment as measured by ultrasound critical angle reflectometry.
AB  - Using an improved version of ultrasound critical angle reflectometry, the bone
      quality of cortical and trabecular bone was assessed in vivo by measuring elastic
      moduli (normalized for bone density) at both principal axes, referred to as the
      minimum and maximum normalized elasticities. The measurements were made in 30
      normal premenopausal women, 30 normal postmenopausal women, 22 untreated
      postmenopausal women with osteoporosis, 74 postmenopausal women with osteoporosis
      or osteopenia on bisphosphonate treatment, and 32 patients with renal
      transplantation (16 women and 16 men) taking steroids. Cortical elasticity was
      higher than trabecular elasticity; both declined slightly and non-significantly
      with age in normal women. Among untreated postmenopausal women with osteoporosis,
      cortical maximum normalized elasticity (E(cmax)) remained within 95% prediction
      intervals of normal women. Among patients on bisphosphonate, E(cmax) was low in
      the majority of patients. E(cmax) was significantly more depressed among those
      taking the drug > or =3 years than <3 years (22.1% below normal premenopausal
      women versus 17.2%, P =0.001), and among those with incident non-spinal fractures
      than without (75.9 vs. 81.5%, P =0.008). E(cmax) was independent of bone mineral
      density at the calcaneus. Most patients with renal transplantation had low
      E(cmax), with a mean 20.8% below the normal premenopausal mean. Qualitatively
      similar findings were found with cortical minimum elasticity and with trabecular
      minimum and maximum elasticities. Thus, the material bone quality of cortical and
      trabecular bone may be impaired following bisphosphonate treatment, as in renal
      transplantation on steroids.

PMID- 15726295
TI  - Vertebral deformity, back symptoms, and functional limitations among older women:
      the Framingham Study.
AB  - Vertebral deformity is the most common manifestation of osteoporosis. The purpose
      of this study was to determine the relation between incident vertebral deformity
      and back symptoms; and limitations in nine specific functional activities.
      Subjects were participants in the Framingham Study, a longitudinal, population
      based sample involving residents of Framingham, MA, USA. Subjects consisted of
      444 surviving female members of the original cohort who had baseline (1968-1975)
      and follow-up (1992-1993) spine radiographs evaluated for deformity using a
      semiquantitative scale. Ages ranged from 72 to 96 years. At the follow-up
      examination, subjects were asked if they experienced pain, aching, or stiffness
      in their back on most days and if they had difficulty performing nine specific
      functional skills. We found that incident vertebral deformity was associated with
      limitations in several functional activities, most notably, pushing or pulling a
      large object (OR 2.51, 95% confidence interval 1.40, 4.52). For most activities,
      there was no increase in the risk of functional limitations among women with
      vertebral deformity who did not report back symptoms at the end of the follow-up
      compared with those without vertebral deformity or back symptoms. For several
      functional activities, individuals with both vertebral deformity and back
      symptoms had greater limitations than would be expected from the additive
      contribution of both conditions. Back symptoms were associated with limitations
      in most functional activities, even in the absence of vertebral deformity.
      Efforts to prevent and treat back pain, independent of vertebral deformity
      status, might help to reduce functional limitations in older women.

PMID- 15726296
TI  - Generalized low bone mass of girls with adolescent idiopathic scoliosis is
      related to inadequate calcium intake and weight bearing physical activity in
      peripubertal period.
AB  - Generalized low bone mass has been well documented in patients with adolescent
      idiopathic scoliosis (AIS). However, studies linking calcium-intake (CA), weight
      bearing physical-activity (PA) and bone mass of AIS are lacking. We aimed to
      study the relationship between CA, PA and bone mass in AIS girls and compared to
      those of healthy non-AIS controls during the peripubertal period. Newly diagnosed
      AIS girls (n=596) aged 11-16 years with Cobb angle >/=10 degrees were recruited
      to compare with age-matched healthy girls (n=302) in a cross-sectional study.
      Anthropometric parameters, pubertal status, CA and PA were assessed. Areal bone
      mass of lumbar spine and femoral neck, and volumetric bone mass of distal radius
      and tibia were determined by dual-energy X-ray absorptiometry and peripheral
      quantitative computed tomography, respectively. The results showed that weight
      and body mass index (BMI) of AIS were lower than the controls (P<0.05). Corrected
      height and arm span of AIS were longer than those of controls from 13 years
      onwards (P<0.02). Median CA of AIS was <410 mg/day across the ages and did not
      differ from the controls (P=0.063). Median PA of AIS (1.6 h/day) was lower than
      the controls (1.8 h/day) (P=0.025). Bone mass of AIS was on average 6.5% lower
      than controls across the ages (P<0.05). CA and PA were significantly correlated
      with bone mass of AIS (P<0.04). Multivariate analysis showed that AIS in girls
      was associated with lower bone mass, and that both CA and PA were independent
      predictors of bone mass in AIS. In conclusion, AIS girls were found to have lower
      body weight and BMI, longer segmental lengths and generalized low bone mass.
      Inadequate calcium intake and weight-bearing physical activity were significantly
      associated with low bone mass in AIS girls during the peripubertal period. The
      importance of preventing generalized osteopenia in the control of AIS progression
      during the peripubertal period warrants further study.

PMID- 15726297
TI  - Laser-assisted three-dimensional surface modifications of titanium implants:
      preliminary data.
AB  - BACKGROUND: Modern implant systems used in the cervical region do not allow for
      the ingrowth of peri-implant mucosa. The aim of the present study was to use a
      laser to modify titanium implants used in that region in order to promote mucosa
      ingrowth, thereby creating a biological barrier against bacterial infection.
      METHODS: A KrF-excimer laser (lambda=248 nm) was used (tau=30 ns, fmax=50 Hz,
      Emax=1.2 J). Craters were generated, under normal atmospheric conditions or in
      vacuum, in the polished regions of 18 Frialit 2 implants. Surface analysis was
      performed using a scanning electron microscope, an energy dispersive X-ray
      technique, and profile analysis. RESULTS: By adjusting the parameters used, it
      was possible to create canals with widths of up to 100 microm and depths of 450
      microm. Canal morphology was influenced by the laser energy and the surrounding
      atmospheric conditions. Irradiation with 3,000 pulses (650 mJ per pulse) resulted
      in rough surfaces under normal atmospheric conditions, whereas these parameters
      resulted in smooth surfaces in vacuum. The surface chemistry was also influenced
      by the laser parameters used. CONCLUSION: Laser-assisted modification of titanium
      surfaces permits fabrication of 3-D surface modifications. The surface chemistry
      can also be influenced, depending upon the parameters chosen. Further studies are
      necessary to evaluate whether ingrowth of mucosa into the canals can be realized.

PMID- 15726299
TI  - [Rashes in HIV-infected patients undergoing therapy with nevirapine or
      efavirenz].
AB  - Efavirenz and nevirapine are frequently used drugs in antiretroviral therapy.
      Rashes are common side effects of these drugs. In this study, we examined the
      characteristics of efavirenz- and nevirapine-associated rashes. This prospective
      nonrandomized multicenter study included 662 HIV-infected patients (efavirenz:
      325, nevirapine: 337) to determine incidence, duration, cross-reactivity, and
      outcome upon reexposure. Of the treated patients, 4.5% (n=30) developed rashes
      (nevirapine: 2.4% and efavirenz: 6.4%). In four patients treatment was not
      interrupted. Three patients were re-exposed to the initial drug without any side
      effects. Therapy with nevirapine or efavirenz does not have to be interrupted if
      rashes exhibit no blistering, mucosal manifestations, or systemic signs.

PMID- 15726298
TI  - Dynamic holographic endoscopy--ex vivo investigations of malignant tumors in the
      human stomach.
AB  - Laser holographic interferometry is based on the superimposition of the holograms
      of different motional states of an object on a single holographic storing medium.
      Using a combination of holographic interferometry and endoscopic imaging, we
      tried to detect areas of focally disturbed tissue elasticity in gastric cancer
      preparations. By connecting a mobile electronic speckle pattern interferometry
      (ESPI) camera system (light source: double frequency Nd:YAG laser, lambda = 532
      nm) to different types of endoscopes, ex vivo experiments were performed on ten
      formalin fixed human stomachs, nine containing adenocarcinomas and one with a
      gastric lymphoma. Linking the endoscopic ESPI camera complex to a fast image
      processing system, the method of double pulse exposure image subtraction was
      applied at a video frame rate of 12.5 Hz. Speckle correlation patterns and
      corresponding phase difference distributions resulting from gastric wall
      deformation by gentle touch with a guide wire were analyzed. Tumor-free gastric
      areas showed high-contrast concentric fringes around the point of stimulation. In
      contrast, fringe patterns and filtered phase difference distributions
      corresponding to the areas of malignancy in all the cases were characterized by
      largely parallel lines, indicating that stimulation of rigid tumor tissue
      primarily led to tilting. Our ex vivo investigations of malignant gastric tumors
      show that the application of dynamic holographic endoscopy makes it possible to
      distinguish areas of malignancy from surrounding healthy tissue based on the
      differences in tissue elasticity.

PMID- 15726300
TI  - [Aging of hair and nails].
AB  - Human hair and nails, like all other organs, undergo chronological aging. Age
      associated changes in growth, color, and structure of the hair and nails are
      common. In contrast to the aging process of the skin, the gerontobiological
      course of hair and nails has not been investigated comprehensively.
      Investigations on signaling pathways important for melanogenesis of the hair
      follicle improve our understanding of processes involved in hair greying.
      Differences in the structure and quality of the nails at an advanced age are
      determined mainly by age-dependent variations in lipid content of the nail
      plates. However, it is important to recognize age-dependent processes in hair
      shafts and nails and to distinguish between chronological aging and pathological
      changes. The possibilities to improve these aging processes have, primarily, to
      be seen in the field of external cosmetic procedures. Since the effect of
      preexisting hormonal substitution treatment has not yet been adequately
      investigated, it can be regarded as critical to evaluate the confirmed benefits
      and possible risks of such treatment either for hair or for nail quality
      improvement.

PMID- 15726301
TI  - [Anti-aging medicine in dermatologic practice].
AB  - In the future, the increasing number of older individuals will play an even
      greater social and medicopolitical role. One challenge for dermatology is to
      incorporate preventive or anti-aging measures into daily practice. Solid
      understanding of the mechanisms of aging is required. An organized approach to
      such patients with emphasis on history, physical examination, imaging and skin
      physiology studies, and laboratory diagnosis is presented. Topical and systemic
      interventions should be based on the results of this complete evaluation.

PMID- 15726302
TI  - [What is anti-aging medicine?].
AB  - The apparent demographic changes in our society with a substantial increase of
      elderly people threatened by restrictions due to diseases, invalidity, and
      disability call for new forms of "active prevention," namely anti-aging medicine.
      This kind of medical intervention is not intended to stop or reverse the aging
      process, but to recognize and decrease the risks of developing chronic diseases
      provoked by genetic disposition, lifestyle, and biochemical changes and to
      initiate preventive strategies. These medical interventions are based on
      knowledge about biological organ functions during the course of a lifetime that
      proceed according to a general time frame: increase of function from birth to the
      age 15-28, followed by a continuous decrease until the "disability threshold" is
      reached, with decompensation of organic function, leading to disease and possibly
      to death. In light of this background, a modular system of prevention was
      generated for practical medicine, including risk calculators for detection of the
      individual health risk and diagnosis of premature loss of organic function using
      specific vitality tests. Finally, a concept of preventive methods was elaborated
      based on scientific and clinical evidence.

PMID- 15726303
TI  - [A rare low-grade malignant scalp tumor. Atypical fibroxanthoma].
AB  - A 79-year-old patient presented with an asymptomatic scalp tumor which had grown
      over the past 9 months. Based on clinical, histological and immunohistochemical
      staining, we made the diagnosis of an atypical fibroxanthoma (AFX). AFX is a rare
      tumor, but important in the differential diagnosis of other scalp tumors. The
      routine histological staining allows one to identify a malignant fibrous
      histiocytoma, while a spindle-cell malignant melanoma can be excluded with
      immunohistochemical staining. An anaplastic squamous cell carcinoma cannot always
      be separated with completed certainty from atypical fibroxanthoma. AFX is a low
      grade malignant tumor and most cases behave in a benign fashion. After complete
      excision, we recommend follow-up for a number of years because of the possibility
      of local recurrence.

PMID- 15726304
TI  - [Antitumour vaccination in patients with ENT tumours. Successful track record].

PMID- 15726305
TI  - [Limitations of anesthesia. Risks and older patients in daily practice].
AB  - The demographic development and ongoing improvement of surgical techniques result
      in an increasing number of high risk elderly patients undergoing surgery. The
      anesthesiologist has an important role within the management of these patients,
      because apart from the present illness resulting in a surgical intervention the
      anesthesiologist has to assess and treat the pre-existing medical disorders in
      the perioperative period. In many cases the pre-existing medical disorders and
      the medications needed for their treatment are more important within the
      anesthesiological management than the operation to be performed. Apart from the
      preoperative assessment of the patients risk in combination with a possible
      optimization of the therapy of the comorbidities, the intra- and postoperative
      management of these high risk patients has an important influence on the
      postoperative rehabilitation of these patients. The adequate perioperative
      anesthesiological management can result in the avoidance of intensive care
      treatment. A very often underestimated topic is the sufficient perioperative pain
      treatment of these high risk elderly patients.

PMID- 15726306
TI  - Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis
      in a Chinese family.
AB  - Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disorder which
      is characterized by periodic attacks of muscle weakness associated with a
      decrease in the serum potassium level. The skeletal muscle calcium channel alpha
      subunit gene CACNA1S is a major disease-causing gene for HypoPP, however, only
      three specific HypoPP-causing mutations, Arg528His, Arg1,239His and Arg1,239Gly,
      have been identified in CACNA1S to date. In this study, we studied a four
      generation Chinese family with HypoPP with 43 living members and 19 affected
      individuals. Linkage analysis showed that the causative mutation in the family is
      linked to the CACNA1S gene with a LOD score of 6.7. DNA sequence analysis
      revealed a heterozygous C to G transition at nucleotide 1,582, resulting in a
      novel 1,582C-->G (Arg528Gly) mutation. The Arg528Gly mutation co-segregated with
      all affected individuals in the family, and was not present in 200 matched normal
      controls. The penetrance of the Arg528Gly mutation was complete in male mutation
      carriers, however, a reduced penetrance of 83% (10/12) was observed in female
      carriers. No differences were detected for age-at-onset and severity of the
      disease (frequency of symptomatic attacks per year) between male and female
      patients. Oral intake of KCl is effective in blocking the symptomatic attacks.
      This study identifies a novel Arg528Gly mutation in the CACNA1S gene that causes
      HypoPP in a Chinese family, expands the spectrum of mutations causing HypoPP, and
      demonstrates a gender difference in the penetrance of the disease.

PMID- 15726307
TI  - Abrupt hypokalemia with paralysis from a clinician's perspective.

PMID- 15726308
TI  - [Predictors for patients' starting psychotherapy].
AB  - BACKGROUND: The aim of this study was to discover prognostic criteria for
      outpatients' making use of psychotherapy. Data from patients and therapists were
      collected. SUBJECTS AND METHODS: After initial psychoanalytic interviews, 92
      patients at a university psychotherapy outpatient department were asked to
      complete narrative forms and standardized questionnaires (FMP) regarding their
      motivation to seek psychotherapy. In addition, the therapists contributed a
      Global Assessment of Functioning (GAF) and estimate of the initial therapeutic
      working alliance (iTAB) for each patient. In the follow-up, we investigated
      patients' actual use of psychotherapy. RESULTS: Sociodemographic variables,
      personality variables, and diagnoses had only minor prognostic relevance, whereas
      therapists' assessments of patient resources for therapeutic relationship and
      work proved to be of high predictive value. CONCLUSION: Positive assessment of a
      patient's ability for therapeutic working alliance in the initial diagnostic
      interview is shown to be an important prognostic factor of a patient's entering
      psychotherapy.

PMID- 15726310
TI  - [Urogenital cancer studies in view of new legislation].
AB  - Harmonization of European GCP-V-related decrees crushed German urogenital cancer
      study activities and has led to complete discontinuation of investigator
      initiated studies since August 2004. For renal cell carcinoma, the two major
      branches of the German cancer society (Deutsche Krebsgesellschaft e.V.), the
      Association for Urogenital Oncology (AUO) and the Association for (Internal)
      Medical Oncology (AIO), founded a Renal Cancer Task Force Group composed of the
      active members of the former "Intergroup Competence Network Renal Carcinoma" (IKN
      N) in the spring of 2004. The resulting intergroup consortium represents an
      overall community of more than 100 German clinical departments that are highly
      experienced in oncological studies and ready to go for future trials. The basic
      ideas of the concept were transparency, multilateral consultations within the
      Task Force, and early involvement of national and international representatives
      of pharmaceutical companies and medical care insurance providers in the process
      of future study developments. Therefore, two pharmaceutical hearings took place
      at the University of Frankfurt.

PMID- 15726309
TI  - [Clip marker placement following MR-guided vacuum biopsy of the breast].
AB  - PURPOSE: The purpose of our study was to determine the placement accuracy,
      usefulness as a guide for wire localization, and long-term stability of tissue
      marker clips following MR-guided vacuum-assisted biopsy (VB) of breast lesions.
      METHODS: During a 2-year period, MR-guided VB with an 11-gauge device was
      performed in 79 lesions. In 26 lesions a marker clip was placed at the biopsy
      site. RESULTS: In 18 cases, the clip was shown to be closely adjacent to the
      lesion on post-interventional MR images. In seven cases in which minor bleeding
      occurred, the clip dislocated (< or =15 mm) in the direction of the needle
      pathway. In one case dislocation in the dorsal direction (< or =5 mm) was
      observed. In eight cases with a malignant or borderline histology according to
      the VB, the marker clips served as targets for mammographically guided wire
      localization. In all of those patients, histology results derived from open
      surgery confirmed those of VB. Eighteen patients with benign findings according
      to the VB were followed up 6 months later. Among these cases we found a
      significant displacement of the marker clip in one case (3 cm). The clip
      generally caused a round artifact (diameter of 9+/-2 mm). In two cases it was not
      possible to determine whether the lesion had been removed completely or was just
      behind the artifact caused by the clip. CONCLUSION: Based on our results, clip
      marker placement following MR-guided vacuum biopsy should be called into question
      due to the possibility of masking the lesion by a metallic artifact and because
      of possible dislocation.

PMID- 15726311
TI  - [Erectile function after nerve-sparing radical prostatectomy. Nocturnal early
      erection as a parameter of postoperative organic erectile integrity].
AB  - The time lapse before recovery of erectile function after nerve-sparing radical
      prostatectomy is still under debate. Several pathophysiologies are postulated for
      postoperative erectile function rehabilitation. In prospective studies we
      measured nocturnal penile tumescence (NPTR) in the acute phase during the first
      night after catheter removal subsequent to nerve-sparing radical prostatectomy to
      assess the neuronal organic erectile integrity. Eighteen sexually active patients
      suffering from local prostate cancer underwent bilateral and unilateral nerve
      sparing retropubic radical prostatectomy. All patients completed an IIEF-5
      questionnaire concerning erectile function preoperatively. The transurethral
      catheter was removed 14 days after surgery, and nocturnal penile tumescence was
      measured with an erectometer (Rigi-Scan) in each patient during the following
      night. None of these patients received any comedication interacting with erectile
      function. The preoperative IIEF score was >18 in all patients. After catheter
      removal, 17 of 18 patients (95%) had nocturnal penile radial rigidity >70% that
      persisted for >10 min during one night. In a control of four patients without a
      nerve-sparing procedure, no nocturnal erections were recorded. The measurement of
      NPTR in the acute phase after nerve-sparing radical prostatectomy showed retained
      erectile function even during the "first" night after catheter removal. Our
      findings are important for an appropriate choice of pharmacotherapy for optimal
      recovery of erectile function. In cases of early penile erections, the cavernous
      nerve had been well preserved during surgery providing good neuronal integrity,
      and PDE-5 inhibitors can support organic rehabilitation of the corpus cavernosum.
      In the absence of early penile erections, the neuronal integrity of the cavernous
      nerve is presumed to be impaired. In this case, additional injection therapy
      should be chosen to support recovery of spontaneous erectile function.

PMID- 15726312
TI  - [Is the prostate cancer screening behaviour of men with familial predisposition
      predictable?].
AB  - Little is known about the motives of German men to attend or refuse preventive
      checkups for prostate cancer. The aims of this study were to investigate if in
      men with familial predisposition screening behaviours are influenced by
      epidemiological or clinical parameters of prostate cancer of their affected
      relatives. 476 probands with one and 312 probands with at least two affected
      relatives were advised in writing to have a PSA-test and DRE done at their local
      urologists. We evaluated if the response rate was correlated to the proband's
      age, to the number and the age of onset of their affected relatives and also to
      the clinical course of their disease. Our data implicate that in men with
      familial predisposition the acceptance of prostate cancer screening is influenced
      only by individual characteristics and personal attitude and not by factors
      within the family. To which extent the awareness of disease risk is modified by
      familial predisposition remains to be evaluated.

PMID- 15726313
TI  - [Phytotherapy for BPS. Which products can still be prescribed?].
AB  - For decades, plant extracts have been amongst to the most popular drugs for lower
      urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH)/benign
      prostatic enlargement (BPE). Only a few of the many published studies meet the
      criteria of the WHO-BPH consensus conference. The few placebo-controlled, long
      term (>/=6 months) studies suggest a positive effect of some extracts (saw
      palmetto, beta-sitosterol, urtica, rye-grass, saw palmetto/urtica combination) on
      LUTS; an effect on uroflow, post-void residual volume, prostate volume and PSA
      was not consistently demonstrable. Randomised trials against an active comparator
      (alpha1-blocker, 5alpha-reductase inhibitors) are difficult to interpret. Due to
      the lack of prospective studies, several meta-analyses have been published that
      can not, however, replace prospective studies. None of the BPH-guidelines
      currently recommend plant extracts, yet universally conclude that this is an
      interesting approach. Further prospective studies using WHO standards are
      required to reliably determine the role of such extracts in the management of
      elderly men with LUTS due to BPH/BPE.

PMID- 15726315
TI  - [Pathophysiology of urge, stress, and mixed incontinence].
AB  - According to the new ICS classification, urinary incontinence is subdivided by
      symptomatic, clinical, and urodynamic criteria. Understanding the
      pathophysiological interactions is important to find the correct diagnosis.
      Disturbances in bladder storage include urge incontinence due to neurogenic or
      non-neurogenic (idiopathic) detrusor hyperactivity as well as stress urinary
      incontinence caused by an insufficient urethral closure mechanism due to reduced
      pressure transmission (active-passive), hypotonic urethra, hyporeactivity of
      sphincter musculature, or involuntary relaxation of the urethra. Stress and urge
      incontinence can occur in combination and then be defined as mixed incontinence.

PMID- 15726314
TI  - [Mesonephric carcinoma of the urethra. A case report].
AB  - Mesonephric carcinoma is a tumor entity that rarely develops in the neck of the
      uterus and vaginal wall and is extremely unusual in the urinary bladder or
      paraurethral tissue. The tumors arise in the remnants of the wolffian or
      mesonephric duct. The malignant potential is considered to be lower than in
      tumors of the urethra with different histologic findings. Anterior pelvic
      exenteration is recommended in the literature as the treatment of choice. In the
      case described here, the tumor presented as a space-occupying lesion in a
      urethral diverticulum exhibiting striking clinical features of macrohematuria and
      urinary retention with subvesical obstruction of the urethra. In accordance with
      reports in the literature, cystectomy was performed and a Kock pouch constructed
      for urinary diversion. Tumors occurring in a diverticulum-and in this case
      manifesting as the rare tumor form of mesonephric carcinoma-should always be
      included in the differential diagnosis of macrohematuria in women.

PMID- 15726317
TI  - Resistance gene analogue markers are mapped to homeologous chromosomes in
      cultivated tetraploid cotton.
AB  - Degenerate primers designed from conserved motifs of known plant resistance gene
      products were used to amplify genomic DNA sequences from the root-knot nematode
      (Meloidogyne incognita) resistance genetic source, Upland cotton (Gossypium
      hirsutum) cultivar Auburn 634 RNR. A total of 165 clones were isolated, and
      sequence analysis revealed 57 of the clones to be novel nucleotide sequences,
      many containing the resistance (R)-protein nucleotide-binding site motif. A
      cluster analysis was performed with resistance gene analogue (RGA) nucleotide
      sequences isolated in this study, in addition to 99 cotton RGA nucleotide
      sequences already deposited in GenBank, to generate a phylogenetic tree of cotton
      R genes. The cotton RGA nucleotide sequences were arranged into 11 groups and 56
      sub-groups, based on genetic distances. Multiple sequence alignments were
      performed on the RGA sequences of each sub-group, and either the consensus
      sequences or individual RGA sequences were used to design 61 RGA-sequence-tagged
      site primers. A recombinant inbred line (RIL) population of cultivated tetraploid
      cotton was genotyped using RGA-specific primers that amplified polymorphic
      fragments between the two RIL parents. Nine RGA markers were mapped to
      homeologous chromosomes 12 and 26, based on linkage to existing markers that are
      located on these chromosomes.

PMID- 15726316
TI  - Identification of functional apple scab resistance gene promoters.
AB  - Apple scab (Venturia inaequalis) is one of the most damaging diseases affecting
      commercial apple production. Some wild Malus species possess resistance against
      apple scab. One gene, HcrVf2, from a cluster of three genes derived from the wild
      apple Malus floribunda clone 821, has recently been shown to confer resistance to
      apple scab when transferred into a scab-susceptible apple variety. For this proof
      of-function experiment, the use of the 35S promoter from Cauliflower mosaic virus
      was reliable and appropriate. However, in order to reduce the amount of non-plant
      DNA in genetically modified apple to a minimum, with the aim of increasing
      genetically modified organism acceptability, these genes would ideally be
      regulated by their own promoters. In this study, sequences from the promoter
      region of the three members of the HcrVf gene family were compared. Promoter
      constructs containing progressive 5' deletions were prepared and used for
      functional analyses. Qualitative assessment confirmed promoter activity in apple.
      Quantitative promoter comparison was carried out in tobacco (Nicotiana glutinosa)
      and led to the identification of several promoter regions with different
      strengths from a basal level to half the strength of the 35S promoter from
      Cauliflower mosaic virus.

PMID- 15726318
TI  - [Five-year results following autogenous osteochondral transplantation to the
      femoral head].
AB  - The rationale for autogenous osteochondral grafting into necrotic areas of the
      femoral head is to provide hyaline cartilage for areas of main articular contact
      pressure. The aim of this study was to present our results of autogenous
      osteochondral grafting to the femoral head in the treatment of avascular
      necrosis. The mean follow-up of the five patients was 57 months following
      autogenous osteochondral grafting to the femoral head using DBCS (diamond bone
      cutting system). The number of transplanted cylinders varied between one and
      three, and the diameter of the cylindrical transplants between 9 and 13 mm.
      Results were unsatisfactory in four of five hips and these underwent total hip
      replacement a mean of 49 months following DBCS of the hip. In our hands,
      osteochondral grafting to the femoral head using DBCS had proven technically
      possible in restoring the articular surface of the femoral head; however, this
      operation was associated with unsatisfactory results in four of five cases.

PMID- 15726319
TI  - [Shoulder dislocation in the newborn. Report of 12 cases and review of the
      literature].
AB  - Shoulder dislocation in the newborn is a rare entity. Therefore, a therapeutic
      regimen does not exist. This retrospective clinical study (1967-2003) includes 9
      newborns with 12 dislocations of the shoulder. The data focus in particular on
      the therapeutic strategy and its success. The position of the joint and its
      functionality were monitored with a questionnaire. Publications from 1904 to 2003
      were reviewed and served for comparison. Results of calculations showed that
      0.018-0.07% of newborns suffer from shoulder dislocations. The diagnosis was made
      on average at the age of 22 days. Our data include four cases each of congenital
      and paralytic and two cases each of spastic and traumatic shoulder dislocations.
      All of them were initially treated conservatively, but because of inadequate
      results one patient finally had to be operated. In the follow-up of 19.4 years,
      none of them developed a redislocation and all shoulder functions were suitable
      for daily life. We propose that patients primarily be treated conservatively;
      however, if therapy fails, surgery has to be performed.

PMID- 15726321
TI  - [Intramuscular angioma in the hand. A case report].
AB  - Intramuscular angiomas are rare vascular tumors with locally aggressive growth
      between the fibers of muscle. A malignant aspect poses a danger for the function
      of the hand. We report the case of a 32-year-old woman with a painless tumor in
      the thenar. Physical examination showed a 2 x 3 x 5 cm fixed and engorged
      swelling. Perfusion and sensibility were intact. The flexion and opposition of
      the thumb were reduced. CAT showed a tumor of the thenar with a solid structure
      with signal enhancement after administration of contrast medium. Histologic
      examination after local resection showed an intramuscular angioma. Intramuscular
      angiomas have a malignant aspect because of the rapid and infiltrative growth
      followed by functional impairment, pain, and deformity. A high rate of recurrence
      is described. Thus, radical excision is indicated.

PMID- 15726320
TI  - [Periprosthetic bone loss after total hip endoprosthesis. Dependence on the type
      of prosthesis and preoperative bone configuration].
AB  - The changes of the periprosthetic bone density were examined with DEXA in 81
      patients over a period of 1 year after implantation of cementless total hip
      endoprosthesis. Four types of endoprostheses (Vision 2000/Duraloc, ALPHA
      Fit/ALPHA-Lock Plus, CLS/Allofit, Mayo/Trilogy) were implanted. Information on
      the changes of the periprosthetic bone density depending on the type of the
      prosthesis and the bony situation at the femur before operation was expected from
      these measurements. In all types of stems the strongest reduction of the bone
      density was found in the region of the calcar femoris, and the smallest changes
      were found distally and medially of the tip of the prostheses. In the prosthesis
      with shorter stem the change of the bone density was altogether clearly lower
      than in prostheses with longer stem. With increasing size of the prosthesis with
      proximally porous coating made from cobalt-chrome alloy, proximal atrophy was
      observed more frequently, whilst in the prosthesis made from titanium alloy with
      completely rough-blasted surface the distal hypertrophy increased. A low
      preoperative corticalis-bone marrow index strengthened the proximal atrophy in
      proximally porously coated prosthesis made from cobalt-chrome alloy and led in
      the prosthesis with completely rough-blasted surface more often to distal
      hypertrophy of the bone.

PMID- 15726322
TI  - [Improving microbiological diagnostics in septic orthopaedic surgery. Comparative
      study of patients receiving systemic antibiotic therapy].
AB  - MATERIAL AND METHODS: This prospective study included 63 patients with confirmed
      infections of soft tissue, joints, bones or implants. During 110 surgical
      interventions, 124 swab and deep tissue sample pairs were taken and analysed
      microbiologically using standard procedures. RESULTS: In 40 patients who had not
      received prior antibiotic treatment, 57 sample pairs (swabs/tissue) were taken.
      In 70%, growth of microorganisms could be observed in both swabs and tissue
      samples. Growth in tissue sample only was observed in 14% and in 14% no growth
      could be detected. In 67 sample pairs taken from 23 patients who had received
      systemic antimicrobial treatment prior to surgery, microbial growth in both
      specimens was detected in 40%. Growth in tissue sample only was observed in 22%
      and 34% of the samples remained without detectable growth. The overall
      sensitivity of the tissue samples (70%) was significantly higher than in swab
      samples (44%) for the pretreated group. CONCLUSION: The use of intraoperative
      tissue samples for microbiological diagnostics in septic orthopaedic surgery must
      be considered a "gold standard". The higher sensitivity of intraoperative tissue
      samples is particularly important in patients receiving systemic antibiotic
      therapy prior to surgical interventions.

PMID- 15726323
TI  - [Fixed posterior subluxation with lateral rotation of the knee joint caused by
      congenital dislocation of the patella in combination with aplasia of the
      posterior cruciate ligament. Case report and review of the literature].
AB  - Congenital dislocation of the patella is very rare. In this anomaly, the patella
      is dislocated to the side of the lateral femoral condylus and cannot be
      repositioned manually. Diagnosis is often made by clinical examination and
      observation of an abnormal gait. We describe the long-term course of treatment in
      a young girl with fixed posterior subluxation with lateral rotation of the knee
      joint caused by congenital dislocation of the patella in combination with aplasia
      of the posterior cruciate ligament. These anomalies of the knee joint were
      corrected incrementally. First, recentralization of the patella was performed by
      open surgery. Subsequently, distraction of the shortened ischiocrural muscles and
      the posterior capsules and ligaments was conducted. This is the first case to be
      described, to the best of our knowledge, of a patient with congenital dislocation
      of the patella in combination with aplasia of the posterior cruciate ligament. We
      describe the successful treatment of such a fixed posterior subluxation and
      lateral rotation of the knee joint.

PMID- 15726325
TI  - End-of-life decisions in ICU and cultural specificities.

PMID- 15726326
TI  - Primary synovial chondromatosis of the shoulder: clinical, arthroscopic and
      histopathological aspects.
AB  - Primary synovial chondromatosis is an uncommon condition, and involvement of the
      glenohumeral joint is rare. Currently, the recommended treatment is arthroscope
      assisted synovectomy and removal of the loose bodies. We report a case with the
      clinical findings, radiographic features, arthroscopic technique for treatment of
      this disease and the main histological appearance of the removed loose bodies. We
      believe this is an easy and safe method for management of this disorder and that
      the support of an experienced pathologist is necessary to avoid differential
      diagnostic problems with the uncommon malignant transformation.

PMID- 15726327
TI  - Symptomatic calcification of the medial collateral ligament of the knee joint: a
      report about five cases.
AB  - Symptomatic calcifications of the rotator cuff tendons is well-known pathologic
      condition. However, pathologic calcifications may involve other structures of the
      locomotor system as well. We report about five patients (age 52-66 years) with a
      painful calcification at the proximal part of the medial collateral ligament of
      the knee joint. All five patients presented with load-dependent pain pretending
      meniscus symptoms, but manual valgus stress provoked severe pain at the medial
      side of the knee. Conventional X-ray examination showed a dense rounded deposit
      at the proximal part of the medial collateral ligament. Initially all patients
      were treated conservatively by needling and infiltration with a local
      anaesthetic. Open resection of the deposit was performed in four patients after
      unsuccessful conservative treatment. Postoperatively all patients were
      immediately free of pain. After a mean follow-up of 6 years (patient 1-4)
      (range=2.5-9.5 years), all patients were still free of pain. Histological
      evaluation of biopsies obtained during surgery showed nodular deposition of
      calcium at the collagen fibres, vascular proliferations and inflammative changes.
      Soft tissue calcifications have to be considered as a rare differential diagnosis
      in patients presenting with medial knee joint pain. Open resection reduces
      symptoms immediately. The histological changes seen were comparable to that
      reported about pathological tendon calcifications of the shoulder. Therefore,
      both conditions might be of the same aetiology.

PMID- 15726328
TI  - Operative treatment of deep chondral defects of the patella: results after
      abrasive arthroplasty and periosteal arthroplasty.
AB  - This prospective, non-randomized study was aimed to evaluate the effects of
      abrasive arthroplasty and periosteal arthroplasty in the treatment of deep
      chondral defects of the patella. A total of 30 patients in group A (13 male, 17
      female, age: 28.7+/-6.9 years) underwent arthroscopic abrasive arthroplasty. The
      other patients in group B (n=17, 11 male, 8 female, age 26.8+/-7.0 years)
      underwent periosteal arthroplasty by an autologous periosteal flap. The maximal
      diameter of the defects was 31.1+/-6.7 (range 20-45 mm). The Lysholm score and
      the intensity of pain were evaluated preoperatively and at the time of follow-up
      (3.1+/-1.1, range 2-5 years). The Tegner activity score was evaluated before
      onset of the symptoms and at the time of follow-up. The Lysholm score increased
      significantly in both groups (in group a from 36.1+/-7.1 to 42.5+/-6.6 points and
      in group B from 42.7+/-2.4 to 67.6+/-7.8 points). The result in group B was
      significantly better than in group A. In group A the intensity of pain was
      unchanged, whereas patients from group B reported a significant reduction of
      pain. The level of physical activity (Tegner score) was 5.5+/-2.1 in group A and
      5.5+/-2.1 in group B before onset of the complaints. In follow-up, patients from
      group B (4.9+/-1.2) had a reduced Tegner score in tendency. The patients in group
      A had a significantly reduced level of physical activity (2.7+/-0.6). A total of
      12 patients from group B had a range of motion lesser than 80 degrees in flexion.
      These patients underwent joint mobilization and control arthroscopy. During
      control arthroscopy there was always found a stable periosteal flap. Short-term
      clinical results with periosteal arthroplasty produced a significant reduction in
      pain and improved Lysholm score in comparison to abrasive arthroplasty.

PMID- 15726330
TI  - Large reallocations of carbon, nitrogen, and photosynthetic reductant among
      phycobilisomes, photosystems, and Rubisco during light acclimation in
      Synechococcus elongatus strain PCC7942 are constrained in cells under low
      environmental inorganic carbon.
AB  - Synechococcus elongatus strain PCC7942 cells were grown in high or low
      environmental concentrations of inorganic C (high-C(i), low-C(i)) and subjected
      to a light shift from 50 micromol m(-2) s(-1) to 500 micromol m(-2) s(-1). We
      quantified photosynthetic reductant (O(2) evolution) and molar cellular contents
      of phycobilisomes, PSII, PSI, and ribulose-1,5-bisphosphate carboxylase oxygenase
      (Rubisco) through the light shift. Upon the increase in light, small initial
      relative decreases in phycobilisomes per cell resulted from near cessation of
      phycobilisome synthesis and their dilution into daughter cells. Thus, allocation
      of reductant to phycobilisome synthesis dropped fivefold from pre- to post-light
      shift. The decrease in phycobilisome synthesis liberated enough material and
      reductant to allow a doubling of Rubisco and up to a sixfold increase in PSII
      complexes per cell. Low-C(i) cells had smaller initial phycobilisome pools and
      upon increased light; their reallocation of reductant from phycobilisome
      synthesis may have limited the rate and extent of light acclimation, compared to
      high-C(i) cells. Acclimation to increased light involved large reallocations of
      C, N, and reductant among different components of the photosynthetic apparatus,
      but total allocation to the apparatus was fairly stable at ca. 50% of cellular N,
      and drew 25-50% of reductant from photosynthesis.

PMID- 15726329
TI  - Patellar polyethylene peg fracture: a case report and review of the literature.
AB  - The patellar component of a total knee replacement (TKR) is the most frequent
      source of non-septic complications after total knee arthroplasty. Fracture of
      patellar pegs in all polyethylene patellar components is a very rare occurrence.
      We report such a case of a patellar polyethylene fracture in a 72-year-old female
      patient 10 years after TKR. Due to patellar malalignment and high level of
      activity, the patellar components failed in this patient. This was treated
      arthroscopically by removing the components that failed and leaving the patella
      unresurfaced. We followed up the patient postoperatively and her symptoms were
      substantially resolved.

PMID- 15726331
TI  - Functional magnetic resonance imaging reveals similar brain activity changes in
      two different animal models of schizophrenia.
AB  - RATIONALE AND OBJECTIVES: In schizophrenia research, most of the functional
      imaging studies have been performed in psychotic patients, but little is known
      about brain areas involved in the expression of psychotic-like symptoms in animal
      models. The objective of this study was to visualize and compare brain activity
      abnormalities in a neurodevelopmental and a pharmacological animal model of
      schizophrenia. METHODS: Blood perfusion of specific brain areas, taken as
      indirect measure of brain activity, was investigated in adult rats following
      either neonatal ventral hippocampal lesion or acute administration of
      phencyclidine. Quantitative perfusion magnetic resonance imaging was performed on
      five frontal brain slices using the continuous arterial spin labeling technique.
      The mean perfusion was calculated in several brain structures, which were
      identified on anatomical images. RESULTS: Lesioned animals exhibiting deficits in
      prepulse inhibition of the startle reflex showed a significant blood perfusion
      increase in the nucleus accumbens, basolateral amygdala, ventral pallidum,
      entorhinal-piriform cortex, orbital prefrontal cortex, and in the bed nucleus of
      the stria terminalis, and a decrease of perfusion in the temporal cortex. Similar
      effects were seen following acute phencyclidine administration in naive animals.
      CONCLUSION: Our data point out specific cortical and subcortical brain areas
      involved in the development of psychotic-like symptoms in two different animal
      models of schizophrenia. The observed brain activity abnormalities are
      reminiscent of classical neuroimaging findings described in schizophrenic
      patients.

PMID- 15726332
TI  - Functional interaction between mGlu 5 and NMDA receptors in a rat model of
      Parkinson's disease.
AB  - RATIONALE: Electrophysiological evidence suggests a synergistic relationship
      between metabotropic (mGlu) and ionotropic (iGlu) glutamate receptors. The
      functional consequences of these interactions have not been investigated in
      neurodegenerative diseases such as in Parkinson's disease. OBJECTIVE: The goals
      of this study are as follows: (1) to investigate the effects of 2-methyl-6
      (phenylethynyl)-pyridine (MPEP) and dizocilpine (MK-801), antagonists at
      metabotropic glutamate 5 (mGlu5) and NMDA receptors, respectively, on the
      akinetic syndrome observed in bilateral 6-OHDA-lesioned rats; (2) to investigate
      if the effects of MPEP were potentiated by co-treatment with a behaviorally
      inactive dose of MK-801; and (3) to investigate the effects of L-DOPA alone and
      in combination with MPEP on the akinetic syndrome observed in 6-OHDA-lesioned
      rats. METHODS: The effects of the different treatments (single and co-treatment)
      administered for 3 weeks were measured in 6-OHDA-lesioned rats trained to release
      a lever rapidly after a visual stimulus onset in a simple reaction time task.
      RESULTS: MPEP 0.75 mg/kg reversed the akinetic deficits produced by striatal
      dopamine depletion, while MPEP 0.375 mg/kg had no effect. Co-administration with
      MK-801 0.02 mg/kg, ineffective alone, failed to speed the recovery process of
      MPEP 0.75 mg/kg but revealed the anti-akinetic action of MPEP 0.375 mg/kg. L-DOPA
      3 mg/kg alone had a potent anti-akinetic effect in 6-OHDA lesioned rats, and this
      effect was not potentiated by a subthreshold MPEP treatment. CONCLUSION: These
      results support a critical role for mGlu5 receptor blockade in improving
      parkinsonian symptomatology either as a single treatment or in combination with
      low concentrations of L-DOPA and demonstrate an interaction between NMDA and
      mGluR5 in regulating these effects.

PMID- 15726333
TI  - A paradigm to investigate the self-regulation of cocaine administration in
      humans.
AB  - INTRODUCTION: Current laboratory paradigms of human cocaine administration
      generally dictate the timing of drug access in ways that may limit assessing
      aspects of cocaine-taking behavior. Patient-controlled analgesia (PCA) methods,
      which allow individuals less restricted access to narcotic (i.e., opiate)
      analgesics, have proven safe and clinically effective for self-regulated
      treatment of pain. The current study assessed the feasibility, safety, and
      validity of a model of ad libitum cocaine self-administration, in which
      participants self-selected the timing of cocaine infusions, using PCA techniques.
      METHODS: Eight nontreatment seeking, otherwise medically healthy, experienced
      cocaine users participated in a double-blind, placebo-controlled, escalating-dose
      regimen of intravenous cocaine (0, 8, 16, and 32 mg per 70 kg) on 4 test days,
      during which time participants had 2 h of access to cocaine via manual presses of
      a corded PCA pump button under a fixed ratio 1: time-out 5-min schedule. RESULTS:
      Procedures were well-tolerated by participants, and no significant adverse events
      were noted. Measures of cocaine self-administration (e.g., number of responses
      and interinfusion intervals) indicated a significant main effect of cocaine dose,
      consistent with predicted dose-response relationships (i.e., decreasing responses
      and increasing interinfusion intervals with increasing injection dose).
      Participants appeared to regulate their cocaine intake in a carefully controlled
      manner, using considerably less cocaine (about half) that permitted by pump
      loading, PCA parameters, and session duration. CONCLUSIONS: Data from this study
      support the validity of our PCA paradigm. Moreover, results suggest the apparent
      feasibility and safety of allowing experienced users to self-select the timing of
      cocaine infusions to intervals as short as 5 min. Such procedures may enhance our
      ability to identify effective pharmacological treatments for cocaine addiction.

PMID- 15726334
TI  - Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial
      stress model for depression.
AB  - RATIONALE: Substance P antagonists have been proposed as candidates for a new
      class of antidepressant compounds. OBJECTIVES: We examined the effects of SLV
      323, a novel neurokinin 1 receptor (NK1R) antagonist, in the chronic psychosocial
      stress paradigm of adult male tree shrews. METHODS: Animals were subjected to a 7
      day period of psychosocial stress before being treated daily with SLV-323 (20 mg
      kg(-1) day(-1)). The psychosocial stress continued throughout the treatment
      period of 28 days. Brain metabolite concentrations were determined in vivo by
      proton magnetic resonance spectroscopy. Norepinephrine excretion was monitored
      from daily urine samples, and serum testosterone concentrations were measured at
      the end of the experiment. All animals were videotaped daily to analyze scent
      marking behavior and locomotor activity. Cell proliferation in the dentate gyrus
      and hippocampal volume were measured postmortem. RESULTS: Stress significantly
      decreased cerebral concentrations of N-acetyl-aspartate, total creatine, and
      choline-containing compounds in vivo and resulted in an increase of urinary
      norepinephrine and decrease of serum testosterone concentrations. Moreover,
      stressed animals displayed decreased scent-marking behavior and locomotor
      activity. The proliferation rate of the granule precursor cells in the dentate
      gyrus was reduced, and hippocampal volume was mildly decreased. The stress
      induced alterations in the central nervous system were partially prevented by
      concomitant administration of SLV-323, while drug treatment had only a minor
      effect on the stress-induced behavioral changes. CONCLUSIONS: The novel NK1R
      antagonist SLV-323 has certain antidepressant-like effects in a valid animal
      model of depression.

PMID- 15726336
TI  - Recent advances in the application of capillary electrophoresis to neuroscience.
AB  - With fast separation times (seconds to minutes), minimal sample requirements
      (nanoliters to femtoliters), and excellent mass detection limits (femtomole to
      zeptomole), capillary electrophoresis (CE) is ideally suited for in vitro and in
      vivo sampling of neurological samples with a high degree of spatial resolution.
      Advances in extracellular fluid analysis employing improved microdialysis and
      push-pull perfusion sampling methodologies has enabled the resolution of
      neurotransmitters present in limited amounts using CE. Great progress has been
      made to resolve complex neuropeptides, amino acids, and biogenic amines in tissue
      and cell cultures. Finally, owing largely to the small volume sampling abilities
      of CE, investigations of single nerve cells, both invertebrate and mammalian,
      have been accomplished. These applications of CE to the advancement of
      neuroscience are presented.

PMID- 15726337
TI  - Peak parking technique for the simultaneous determination of anions and cations.
AB  - An ion chromatography method is described for the simultaneous determination of
      anions (Cl-, NO3-, and SO4(2-)) and cations (Na+, NH4+, K+, Mg2+, and Ca2+) using
      a single pump, a single eluent and a single detector. An anion-exchange column
      modified with chondroitin sulfate C facilitated the elution of the above three
      anions using 5 mM tartaric acid as the eluent in isocratic mode, whereas the same
      eluent facilitated the separation of the above five cations on a commercially
      available cation-exchange column. The separation columns were connected in series
      via two six-port switching valves, so the required cation-exchange or anion
      exchange separation could be carried out by selecting the appropriate positions
      for the switching valves. The separations were completed in 30 min.

PMID- 15726335
TI  - Serotonin transport kinetics correlated between human platelets and brain
      synaptosomes.
AB  - RATIONALE: Blood platelets have been used extensively as a model system for
      investigating the role of the serotonin transporter (SERT) in various psychiatric
      disorders, especially depression. However, to date, it is not known whether
      platelet serotonin (5-HT) transport would be related to that in brain.
      OBJECTIVES: We examined 5-HT transport kinetics simultaneously in human blood
      platelets and human cortical brain synaptosomes to determine whether they were
      correlated. METHODS: Blood platelets and synaptosomes were obtained from 25
      patients undergoing epileptic surgery. Synaptosomes were obtained from normal
      margins of surgical neuropathology specimens of anterotemporal cortex. RESULTS:
      Platelet SERT V(max) was significantly correlated with brain SERT V(max) on
      linear regression (r=0.58, p<0.005), after controlling for the confounding
      effects of gender (t=-2.4, p=0.025) and time of day (t=2.1, p<0.05). Consistent
      with previous observations, there was a negative correlation between the maximum
      velocity (V(max)) of platelet 5-HT transport and pO2 (r=-0.52, p<0.01). Females
      had a significantly higher pO2 than males (F=4.9, p<0.05). After accounting for
      gender differences, addition of pO2 did not add further strength to the
      regression, given the aforementioned gender differences in pO2. The correlation
      between unadjusted values for platelet vs brain SERT V(max) was r=0.3, p=0.06.
      CONCLUSIONS: These results suggest that a relationship may exist between 5-HT
      transport in platelets and cortical synaptosomes, when appropriate controls for
      confounding factors are employed.

PMID- 15726338
TI  - Calibration of NO sensors for in-vivo voltammetry: laboratory synthesis of NO and
      the use of UV-visible spectroscopy for determining stock concentrations.
AB  - The increasing scientific interest in nitric oxide (NO) necessitates the
      development of novel and simple methods of synthesising NO on a laboratory scale.
      In this study we have refined and developed a method of NO synthesis, using the
      neutral Griess reagent, which is inexpensive, simple to perform, and provides a
      reliable method of generating NO gas for in-vivo sensor calibration. The
      concentration of the generated NO stock solution was determined using UV-visible
      spectroscopy to be 0.28+/-0.01 mmol L(-1). The level of NO(2) (-) contaminant,
      also determined using spectroscopy, was found to be 0.67+/-0.21 mmol L(-1).
      However, this is not sufficient to cause any considerable increase in oxidation
      current when the NO stock solution is used for electrochemical sensor calibration
      over physiologically relevant concentrations; the NO sensitivity of bare Pt-disk
      electrodes operating at +900 mV (vs. SCE) was 1.08 nA micromol(-1) L, while that
      for NO(2) (-) was 5.9 x 10(-3) nA micromol(-1) L. The stability of the NO stock
      solution was also monitored for up to 2 h after synthesis and 30 min was found to
      be the time limit within which calibrations should be performed.

PMID- 15726339
TI  - Multianalyte bioanalytical devices: scientific potential and business
      requirements.

PMID- 15726340
TI  - Influence of gap and overlap paradigms on saccade latencies and vergence eye
      movements in seven-year-old children.
AB  - The latency of eye movements is influenced by the fixation task; when the
      fixation stimulus is switched off before the target presentation (gap paradigm)
      the latency becomes short and express movements occur. In contrast, when the
      fixation stimulus remains on when the target appears (overlap paradigm), eye
      movement latency is longer. Several previous studies have shown increased rates
      of express saccades in children; however the presence of an express type of
      latency for vergence and combined movements in children has never been explored.
      The present study examines the effects of the gap and the overlap paradigms on
      horizontal saccades at far (150 cm) and at close (20 cm) viewing distances, on
      vergence along the median plane, and on saccades combined with convergence or
      divergence in 15 normal seven-year-old children. The results show that the gap
      paradigm produced shorter latency for all eye movements than the overlap
      paradigm, but the difference was only significant for saccades at close viewing
      distances, for divergence (pure and combined), and for saccades combined with
      vergence. The gap paradigm produced significantly higher rates of express
      latencies for saccades at close viewing distances, for divergence, and for
      saccades combined with divergence; in contrast, the frequencies of express
      latencies for saccades at far viewing distances and for convergence (pure or
      combined) were similar in the gap and the overlap paradigms. Interestingly, the
      rate of anticipatory latencies (<80 ms) was particularly high for divergence in
      the gap paradigm. Our collective findings suggest that the initiation of saccades
      at close viewing distances and of divergence is more reflexive, particularly in
      the gap paradigm. The finding of frequent anticipatory divergence that occurs at
      similar rates for seven-year-old children (this study) and for adults (Coubard et
      al., 2004, Exp Brain Res 154:368-381) indicates that predictive initiation of
      divergence is dominant.

PMID- 15726341
TI  - Spatial auditory attention is modulated by tactile priming.
AB  - Previous studies have shown that cross-modal processing affects perception at a
      variety of neuronal levels. In this study, event-related brain responses were
      recorded via whole-head magnetoencephalography (MEG). Spatial auditory attention
      was directed via tactile pre-cues (primes) to one of four locations in the
      peripersonal space (left and right hand versus face). Auditory stimuli were white
      noise bursts, convoluted with head-related transfer functions, which ensured
      spatial perception of the four locations. Tactile primes (200-300 ms prior to
      acoustic onset) were applied randomly to one of these locations. Attentional load
      was controlled by three different visual distraction tasks. The auditory P50m
      (about 50 ms after stimulus onset) showed a significant "proximity" effect
      (larger responses to face stimulation as well as a "contralaterality" effect
      between side of stimulation and hemisphere). The tactile primes essentially
      reduced both the P50m and N100m components. However, facial tactile pre
      stimulation yielded an enhanced ipsilateral N100m. These results show that
      earlier responses are mainly governed by exogenous stimulus properties whereas
      cross-sensory interaction is spatially selective at a later (endogenous)
      processing stage.

PMID- 15726343
TI  - Reproductive results associated with misoprostol and other substances utilized
      for interruption of pregnancy.

PMID- 15726342
TI  - Control of finger force direction in the flexion-extension plane.
AB  - We have examined the interaction among individual finger forces in tasks that
      required the production of the total force by a subset of fingers in a particular
      direction in the flexion-extension plane. Nine subjects produced fingertip forces
      in a prescribed direction with a maximum voluntary contraction (MVC) effort and
      held the peak force for two seconds. Six finger combinations were tested, four
      single-finger tasks--Index (I), Middle (M), Ring (R) and Little (L)--one two
      digit task (IM), and one four-digit task (IMRL). The subjects were asked to
      generate the finger forces in two directions, 0 degrees (perpendicular to the
      surface of the transducer) and 15 degrees toward the palm. In all task
      conditions, there were two experimental sessions, with and without visual
      feedback on the task force vector. The main findings were: 1. The target
      direction significantly affected the constant error (CE) but not the variable
      error (VE) while removal of the feedback resulted in an increase in VE. 2. The
      direction of the forces produced by fingers that were not explicitly required to
      produce force (enslaved fingers) depended on the target direction. 3. In multi
      finger tasks, the individual fingers produced force in directions that could
      differ significantly from the target direction, while the resultant force pointed
      in the target direction. There was a negative co-variation among the deviations
      of the directions of the individual finger forces from the target direction. If a
      finger force vector deviated from the target, another finger force vector was
      likely to deviate in the opposite direction. We conclude that a multi-finger
      synergy is involved in the control of the finger force direction.

PMID- 15726344
TI  - Incidence of drug-induced liver injury in medical inpatients.
AB  - OBJECTIVES: Drug-induced liver injury (DILI) is a common concern. However, data
      on DILI epidemiology in inpatients are sparse. METHODS: To investigate the
      incidence of DILI, we screened all patients in the pharmacoepidemiological
      inpatient database according to the CIOMS (Council for International Organisation
      of Medical Science) criteria, which consist of the evaluation of some clinical
      chemistry laboratory liver parameters (CIOMS laboratory criteria) and the
      exclusion of any disease-related causes for the liver injury. Thus, only cases
      with probable or certain causality according to the World Health Organization
      criteria were included. RESULTS: Among a total of 6383 patients, liver parameters
      were determined in 4610, and 489 among them fulfilled the CIOMS laboratory
      criteria. However, 401 patients had to be excluded because of disease-related
      liver injury and, thus, the study cohort consisted of 4209 patients at risk for
      DILI. Among a total of 88 DILI cases, 31 had no documented normal baseline liver
      parameters and, thus, represented prevalent cases. The remaining 57 represented
      incident DILI cases. Thus, the incidence of DILI was 1.4% (95% CI 1.0, 1.7). The
      drug classes most frequently causing DILI were heparins, antibacterials,
      tuberculostatics and antineoplastic agents. Among those, antineoplastic agents
      and tuberculostatics showed the highest incidence. Liver injury was not mentioned
      among the diagnoses or in the physician's discharge letter in about 52-68% of all
      cases. CONCLUSION: Approximately 1 in 100 patients develops DILI during
      hospitalisation in a department of medicine. Incidences of DILI were highest for
      antineoplastic agents and tuberculostatics. DILI is frequently missed and,
      therefore, DILI detection by diagnoses will result in misleadingly low incidence
      rates.

PMID- 15726345
TI  - Neonates do not need to be handled for radiographs.
AB  - BACKGROUND: The handling of sick neonates may have detrimental effects such as
      hypoxia or bradycardia. Such handling is inevitable due to the frequent need for
      practical procedures; however, minimising handling reduces these adverse events
      and may improve outcome. Radiography is one of the commonest procedures performed
      on neonates. Usually the infant is lifted and placed onto the radiographic
      cassette; however, modern incubators often incorporate a tray beneath the
      mattress in which the radiographic cassette can be placed without the need to
      disturb the infant. OBJECTIVE: To compare the quality of chest radiographs taken
      using the standard direct contact method, with those taken using the under-tray
      technique. MATERIALS AND METHODS: A series of chest radiographs taken over a 21
      month period were analysed independently by two consultant paediatric
      radiologists unaware of the radiographic details. The position of the radiograph,
      i.e. direct contact or under-tray, was determined by the radiographer.
      Radiographic quality was scored on the following features: exposure, blurring,
      rotation, cut-off or coning, and side markers. A subjective score was also
      included. The results from each radiologist were analysed separately. RESULTS:
      Seventy chest radiographs were analysed-25 standard method, 45 under-tray. A
      statistically significant advantage for the under-tray method was seen on two
      analyses-radiologist 1 for exposure, and radiologist 2 for cut-off. No other
      significant differences were noted. There were no differences in the infants'
      weights or radiation exposure. CONCLUSIONS: The under-tray method for taking
      radiographs may produce films of at least equivalent quality to the standard
      method. Since the standard method involves handling with potential desaturation
      and bradycardia, this technique should cease.

PMID- 15726346
TI  - Acute hypoxia differentially regulates K(+) channels. Implications with respect
      to cardiac arrhythmia.
AB  - The first ion channels demonstrated to be sensitive to changes in oxygen tension
      were K(+) channels in glomus cells of the carotid body. Since then a number of
      hypoxia-sensitive ion channels have been identified. However, not all K(+)
      channels respond to hypoxia alike. This has raised some debate about how cells
      detect changes in oxygen tension. Because ion channels respond rapidly to hypoxia
      it has been proposed that the channel is itself an oxygen sensor. However,
      channel function can also be modified by thiol reducing and oxidizing agents,
      implicating reactive oxygen species as signals in hypoxic events. Cardiac ion
      channels can also be modified by hypoxia and redox agents. The rapid and slow
      components of the delayed rectifier K(+) channel are differentially regulated by
      hypoxia and beta-adrenergic receptor stimulation. Mutations in the genes that
      encode the subunits for the channel are associated with Long QT syndrome and
      sudden cardiac death. The implications with respect to effects of hypoxia on the
      channel and triggering of cardiac arrhythmia will be discussed.

PMID- 15726347
TI  - Patterns of variability at the major histocompatibility class II alpha locus in
      Atlantic salmon contrast with those at the class I locus.
AB  - In order to investigate the mechanisms creating and maintaining variability at
      the major histocompatibility (MH) class II alpha (DAA) locus we examined patterns
      of polymorphism in two isolated Atlantic salmon populations which share a common
      post-glacial origin. As expected from their common origin, but contrary to the
      observation at the MH class I locus, these populations shared the majority of DAA
      alleles: out of 17 sequences observed, 11 were common to both populations.
      Recombination seems to play a more important role in the origin of new alleles at
      the class II alpha locus than at the class I locus. A greater than expected
      proportion of sites inferred to be positively selected (potentially peptide
      binding residues, PBRs) were found to be involved in recombination events,
      suggesting a mechanism for increasing MH variability through an interaction
      between recombination and natural selection. Thus it appears that although
      selection and recombination are important mechanisms for the evolution of both
      class II alpha and class I loci in the Atlantic salmon, the pattern of
      variability differs markedly between these classes of MH loci.

PMID- 15726348
TI  - A novel nicotinoprotein aldehyde dehydrogenase involved in polyethylene glycol
      degradation.
AB  - A gene (pegC) encoding aldehyde dehydrogenase (ALDH) was located 3.4 kb upstream
      of a gene encoding polyethylene glycol (PEG) dehydrogenase (pegA) in Sphingomonas
      macrogoltabidus strain 103. ALDH was expressed in Escherichia coli and purified
      on a Ni-nitrilotriacetic acid agarose column. The recombinant enzyme was a
      homotetramer consisting of four 46.1-kDa subunits. The alignment of the putative
      amino acid sequence of the cloned enzyme showed high similarity with a group of
      NAD(P)-dependent ALDHs (identity 36-52%); NAD-binding domains (Rossmann fold and
      four glycine residues) and catalytic residues (Glu225 and Cys259) were well
      conserved. The cofactor, which was extracted from the purified enzyme, was
      tightly bound to the enzyme and identified as NADP. The enzyme contained 0.94 mol
      NADP per subunit. The enzyme was activated by Ca(2+), but by no other metals; no
      metal (Zn, Fe, Mg, or Mn) was detected in the purified recombinant enzyme.
      Activity was inhibited by p-chloromercuric benzoate, and heavy metals such as Hg,
      Cu, Pb and Cd, indicating that a cysteine residue is involved in the activity.
      Enzyme activity was independent of N,N-dimethyl-p-nitrosoaniline as an electron
      acceptor. Trans-4-(N,N-dimethylamino)-cinnamaldehyde was not oxidized as a
      substrate, but the compound worked as an inhibitor for the enzyme, as did
      pyrazole. The enzyme acted on n-aldehydes C(2)-C(14)) and PEG-aldehydes. Thus the
      enzyme was concluded to be a novel Ca(2+)-activating nicotinoprotein (NADP
      containing) PEG-aldehyde dehydrogenase involved in the degradation of PEG in S.
      macrogoltabidus strain 103.

PMID- 15726349
TI  - Recombinant production of serine hydroxymethyl transferase from Streptococcus
      thermophilus and its preliminary evaluation as a biocatalyst.
AB  - The glyA gene encoding a serine hydroxymethyl transferase (SHMT) with threonine
      aldolase activity was isolated from Streptococcus thermophilus YKA-184
      chromosomal DNA. This aldolase is a pyridoxal 5'-phosphate-dependent enzyme that
      stereospecifically catalyzes the interconversion of L-threonine to glycine and
      acetaldehyde. The enzyme was overexpressed in Escherichia coli M15 as a
      recombinant protein of 45 kDa with a His6-tag at its N-terminus. The recombinant
      enzyme was purified to homogeneity by a single chromatographic step using Ni
      nitrilotriacetic acid affinity, obtaining a high activity-recovery yield (83%).
      Lyophilized and precipitated enzymes were stable at least for 10 weeks when
      stored at -20 degrees C and 4 degrees C. It was observed that the Km for L-allo
      threonine was 38-fold higher than that for L-threonine, suggesting this enzyme
      can be classified as a specific L-allo-threonine aldolase. The optimum pH range
      of threonine aldolase activity for the recombinant SHMT was pH 6-7. When tested
      for aldol addition reactions with non-natural aldehydes, such as
      benzyloxyacetaldehyde and (R)-N-Cbz-alaninal, two possible beta-hydroxy-alpha
      amino acid diastereoisomers were produced, but with moderate stereospecificity.
      The enzyme showed potential as a biocatalyst for the stereoselective synthesis of
      beta-hydroxy-alpha-amino acids.

PMID- 15726351
TI  - Is whole-body FDG-PET valuable for health screening? Against.

PMID- 15726350
TI  - Medicinal mushroom modulators of molecular targets as cancer therapeutics.
AB  - Empirical approaches to discover anticancer drugs and cancer treatments have made
      limited progress in the past several decades in finding a cure for cancer. The
      expanded knowledge of the molecular basis of tumorigenesis and metastasis,
      together with the inherently vast structural diversity of natural compounds found
      in mushrooms, provided unique opportunities for discovering new drugs that
      rationally target the abnormal molecular and biochemical signals leading to
      cancer. This review focuses on mushroom low-molecular-weight secondary
      metabolites targeting processes such as apoptosis, angiogenesis, metastasis, cell
      cycle regulation, and signal transduction cascades. Also discussed in this review
      are high-molecular-weight polysaccharides or polysaccharide-protein complexes
      from mushrooms that appear to enhance innate and cell-mediated immune responses,
      exhibit antitumor activities in animals and humans, and demonstrate the
      anticancer properties of selenium compounds accumulated in mushrooms.

PMID- 15726352
TI  - Is whole-body FDG-PET valuable for health screening? For.

PMID- 15726354
TI  - Differences and similarities between coronary atherosclerosis and ischaemic heart
      disease: implications for cardiac imaging.

PMID- 15726353
TI  - Positron tomographic assessment of androgen receptors in prostatic carcinoma.
AB  - PURPOSE: The purpose of this study was to evaluate the feasibility of androgen
      receptor (AR) imaging with 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT)
      by positron emission tomography (PET) and to assess the binding selectivity of
      FDHT to AR in patients with prostate cancer. METHODS: Twenty men (age range 56-87
      years) with advanced prostate cancer were studied. All except one had metastatic
      disease confirmed by biopsy and/or radiological studies. One patient who had
      radiological findings suggesting a single hepatic metastasis was found to have
      focal fatty infiltration on biopsy obtained after FDHT-PET and was excluded from
      further data analysis. FDHT uptake was assessed semiquantitatively by
      determination of the standardized uptake value (SUV) and tumor-to-muscle ratio
      (T/M). Additionally, to assess the AR binding selectivity of FDHT, patients with
      one or more foci of abnormally increased FDHT accumulation were studied after
      administration of an AR antagonist (flutamide). RESULTS: Conventional imaging
      demonstrated innumerable lesions in two patients and 43 lesions in the remaining
      17 patients with advanced prostate cancer. FDHT-PET was positive in 12 of 19
      patients (sensitivity of 63%), including the two patients with innumerable
      lesions. FDHT-PET detected 24 of 28 known lesions (86%) in the remaining ten
      patients. In addition, FDHT-PET detected 17 unsuspected lesions in five of these
      ten patients. All 12 patients with positive FDHT-PET underwent a repeat PET study
      after receiving flutamide for 1 day (250 mg t.i.d.). In all of these patients,
      there was a decrease in tumor FDHT uptake after flutamide; the mean (+/- standard
      deviation) SUV and T/M decreased from 7.0+/-4.7 and 6.9+/-3.9, respectively, to
      3.0+/-1.5 and 3.0+/-1.6, respectively (p=0.002). The mean PSA in patients with
      positive FDHT-PET was significantly higher than that in patients with negative
      FDHT-PET (p=0.006). CONCLUSION: Our results document the feasibility of PET
      imaging of prostate cancer with FDHT and suggest that tumor uptake of FDHT is a
      receptor-mediated process. Positive PET studies were associated with higher PSA
      levels and thus, presumably, with greater tumor burden.

PMID- 15726355
TI  - Role of ultrasound in the detection of apoptosis.

PMID- 15726356
TI  - Role of 18F-FDG PET-CT imaging for the detection of an unknown primary tumour:
      preliminary results in 21 patients.
AB  - PURPOSE: Metastatic cancer of unknown primary origin is a syndrome characterised
      by a poor prognosis, with a typical survival rate from diagnosis of no longer
      than 1 year. Only 20-27% of primary tumours are identified by conventional
      radiological imaging. By contrast, it has been reported that 18F
      fluorodeoxyglucose positron emission tomography (FDG PET) allows the
      identification of 24-40% of otherwise unrecognised primary tumours. To our
      knowledge, the studies on this topic have been conducted using 18F-FDG PET
      imaging alone. The aim of this study was to evaluate the potential additional
      diagnostic role of fused 18F-FDG PET-CT imaging for the detection of metastatic
      occult primary tumours. METHODS: The study population consisted of 21 consecutive
      patients with biopsy-proven metastatic disease and negative conventional
      diagnostic procedures. Each patient underwent a PET scan, carried out according
      to a standard procedure (6 h of fasting, i.v. injection of 370 MBq of 18F-FDG and
      image acquisition with a dedicated PET-CT scanner for 4 min per bed position).
      RESULTS: 18F-FDG PET-CT detected the occult primary tumour in 12 patients (57% of
      cases), providing a detection rate higher than that reported with any other
      imaging modality, including conventional 18F-FDG PET. CONCLUSION: The favourable
      results of this study need to be confirmed in larger patient populations with
      long-term follow-up.

PMID- 15726357
TI  - Occult lung infarction may induce false interpretation of 18F-FDG PET in primary
      staging of pulmonary malignancies.
AB  - PURPOSE: The aim of the present report is to describe abnormal (18)F
      fluorodeoxyglucose (FDG) accumulation patterns in the pleura and lung parenchyma
      in a group of lung cancer patients in whom lung infarction was present at the
      time of positron emission tomography (PET). METHODS: Between November 2002 and
      December 2003, a total of 145 patients (102 males, 43 females; age range 38-85
      years) were subjected to whole-body FDG PET for initial staging (n=117) or
      restaging (n=11) of lung cancer or for evaluation of solitary pulmonary nodules
      (n=17). Of these patients, 24 displayed abnormal FDG accumulation in the lung
      parenchyma that was not consistent with the primary lesion under investigation
      (ipsilateral n=12, contralateral n=9 or bilateral n=3). Without correlative
      imaging, this additional FDG uptake would have been considered indeterminate in
      differential diagnosis. RESULTS: Of the 24 patients who were identified as having
      such lesions, six harboured secondary tumour nodules diagnosed as metastases,
      while in three the diagnosis of a synchronous second primary lung tumour was
      established. Additionally, nine patients were identified as having post-stenotic
      pneumonia and/or atelectasis (n=6) or granulomatous lung disease (n=3). In the
      remaining six (4% of all patients), a diagnosis of recent pulmonary embolism that
      topographically matched the additional FDG accumulation (SUV(max) range 1.4-8.6,
      mean 3.9) was made. Four of these six patients were known to have pulmonary
      embolism, and hence false positive interpretation was avoided by correlating the
      PET findings with those of the pre-existing diagnostic work-up. The remaining two
      patients were harbouring small occult infarctions that mimicked satellite nodules
      in the lung periphery. Based on histopathological results, the abnormal FDG
      accumulation in these two patients was attributed to the inflammatory reaction
      and tissue repair associated with the pathological cascade of pulmonary embolism.
      CONCLUSION: In patients with pulmonary malignancies, synchronous lung infarction
      may induce pathological FDG accumulation that can mimic active tumour
      manifestations. Identifying this potential pitfall may allow avoidance of false
      positive FDG PET interpretation.

PMID- 15726358
TI  - Role of tumor-derived transforming growth factor-beta1 (TGF-beta1) in site
      dependent tumorigenicity of murine ascitic lymphosarcoma.
AB  - An ascitic lymphosarcoma (LS-A) of Swiss mice that regressed spontaneously on
      subcutaneous (s.c.) transplantation was investigated for the mechanism of its
      progressive growth and host mortality on intraperitoneal (i.p.) transplantation.
      In vitro studies indicated significant inhibition of LS-A proliferation seeded at
      higher cell density (>10(4)/ml). Culture supernatants of LS-A caused bi-modal
      growth effects, the early supernatants (24 h) caused stimulation and the late (72
      h) supernatants inhibited LS-A proliferation. The 72-h supernatants also
      suppressed T and B cell response to mitogens in a dose-dependent manner. Pan anti
      transforming growth factor-beta antibody abrogated the inhibitory effects of
      supernatants. The supernatants contained both latent as well as bio-active form
      of transforming growth factor-beta1 (TGF-beta1) as determined by ELISA. Mice
      bearing i.p. ascites tumor had elevated serum TGF-beta1, hemoglobulinemia,
      splenic lymphopenia, impaired response of the T cells to mitogen and reduced
      expression of transferrin receptor (CD71) on the bone marrow cells. However, mice
      which rejected s.c. transplants, did not show significant changes in these
      parameters. Our studies indicated profound influence of site of tumor growth on
      tumor progression and host immune system mediated by tumor-derived TGF-beta1. It
      is possible that human tumors which secrete TGF-beta1 may exhibit similar patho
      physiological effects in the host depending on the anatomical site of the tumor.

PMID- 15726359
TI  - Immuno-gene therapy of melanoma by tumor antigen epitope modified IFN-gamma.
AB  - Cytokine-based vaccines play a major part in tumor immuno-gene therapy. However,
      down-regulated antigen expression on tumor cells may diminish the immuno
      potentiating aspects of cellular vaccines. In this study, we coexpressed a tumor
      antigen epitope with IFN-gamma in the same gene by replacing the IFN-gamma signal
      peptide with an antigen epitope-expressing signal peptide. We then investigated
      the effect of the antigen epitope-incorporated IFN-gamma on the immunotherapy of
      murine melanoma B16 tumors. Results showed that TRP-2 epitope-expressing IFN
      gamma decreased B16 tumorigenicity and enhanced its immunogenicity after gene
      transfer. Protective immunity against wild type B16 tumors was induced by
      vaccination with IFN-gamma transiently gene-modified tumor cells. These data
      suggest that cellular vaccines engineered to express an antigen epitope within an
      immunostimulatory cytokine could potentiate the immunization effect.

PMID- 15726360
TI  - Identification of a potential human telomerase reverse transcriptase-derived, HLA
      A1-restricted cytotoxic T-lymphocyte epitope.
AB  - The catalytic subunit of human telomerase reverse transcriptase (hTERT) is
      expressed in the majority of tumor cells of different histological origins as
      opposed to most normal somatic cells. This implicates hTERT as a widely expressed
      tumor-associated antigen and an attractive candidate for antigen-specific tumor
      immunotherapy. T lymphocytes specific for hTERT-derived epitopes have been
      isolated and shown reactive with hTERT-expressing tumor cells. To further
      increase the applicability of hTERT as a target antigen for immunotherapy, we set
      out to identify potential hTERT-derived, HLA-A1-restricted cytotoxic T-lymphocyte
      (CTL) epitopes. The "reverse immunology" approach, involving computer-assisted
      epitope prediction, in vitro CTL induction, and tetramer-guided CTL isolation,
      resulted in specific CTLs against hTERT-derived, HLA-A1-binding peptides.
      Intermediate- to low-avidity CTLs were induced against the hTERT325-333 peptide
      and recognized endogenously processed hTERT. Recognition of endogenous hTERT
      depended on an increase of hTERT expression above normal levels in tumor cells
      through hTERT transduction, most probably as a result of limited CTL avidity. The
      altered peptide ligand hTERT699T-707 was designed to increase HLA-A1-binding
      affinity of the hTERT699-707 peptide and was used to induce CTLs. However, these
      CTLs poorly cross-recognized native hTERT699-707 and failed to recognize
      endogenously processed hTERT. In conclusion, our study has identified the
      hTERT325-333 peptide as a potential hTERT-derived epitope that may prove useful
      for induction and monitoring of hTERT-specific, HLA-A1-restricted CTL responses.

PMID- 15726362
TI  - Long-term results of autologous stem cell transplantation for Hodgkin's disease
      (HD) and low-/intermediate-grade B non-Hodgkin's lymphoma (NHL): a report from
      the Austrian Stem Cell Transplantation Registry (ASCTR).
AB  - Between 1990 and 2001, 68 patients with advanced Hodgkin's disease (HD) and 86
      patients classified as low-/intermediate-grade B non-Hodgkin's lymphoma (NHL)
      were reported to the Austrian Stem Cell Transplantation Registry (ASCTR).
      Following autologous stem cell transplantation (SCT) for HD, overall survival was
      56% [95% confidence interval (CI): 40-72%] with a disease-/progression-free
      survival of 49%, reaching a plateau at 5 years. Using multivariate Cox regression
      analysis BEAM conditioning (carmustine, cytarabine, etoposide and melphalan) was
      predictive for favourable outcome, better disease-/progression-free survival and
      a significantly lower risk for relapse. The cumulative incidence of relapse was
      30%, even for patients in complete remission at time of SCT. The cumulative risk
      for developing a secondary malignancy increased continuously over time, achieving
      20% at 7 years and 46% at 10 years with previous radiotherapy as the only risk
      factor in the multivariate analysis. Overall survival for NHL patients was 45%
      (95% CI: 26-64%) with a disease-/progression-free survival of 26% at 7 years. In
      the multivariate Cox regression analysis stage of disease at time of SCT was the
      most powerful parameter for overall survival, disease-/progression-free survival
      and relapse. Mantle cell lymphoma, greater than or equal to three lines of
      previous therapy, and a conditioning regimen other than BEAM were also predictive
      for death. The main reason for treatment failure was relapse (cumulative
      incidence 54-75%). Because of the high risk of relapse/progression in both
      disease categories and the additional high rate of second malignancies in HD
      patients, allogeneic stem cells should be considered a valuable alternative for
      selected patients. The efficacy of allotransplantation following reduced
      intensity conditioning should be tested in randomised trials.

PMID- 15726361
TI  - Thomsen-Friedenreich (TF) antigen as a target for prostate cancer vaccine:
      clinical trial results with TF cluster (c)-KLH plus QS21 conjugate vaccine in
      patients with biochemically relapsed prostate cancer.
AB  - The differential overexpression of self-antigens on tumor cells is a prime
      feature of malignant transformation. Thomsen-Friedenreich (TF), a core
      disaccharide of O-glycosylated complex glycoproteins, is one of many "self"
      antigens expressed on malignantly transformed cells that has served as a target
      for immune recognition and attack. Previously, we conducted clinical trials with
      a series of synthetic glycolipid, peptide and carbohydrate antigens conjugated to
      the immunological carrier keyhole limpet hemocyanin (KLH) mixed with the
      immunological saponin adjuvant, QS21. These trials resulted in the generation of
      high-titer IgM and IgG antibody responses specific for the individual antigens,
      and, in several cases, the capacity of those antibodies to mediate complement
      lysis. Four groups of five patients who had evidence of a biochemical relapse
      defined as rising prostate-specific antigens (PSAs) following primary therapy for
      prostate cancer with either prostatectomy or radiation were treated with
      escalating doses of 1, 3, 10 and 30 microg of synthetic TF in a clustered
      formation (c) which was conjugated to KLH and given with 100 microg of QS21.
      Patients received a total of five subcutaneous vaccines over 6 months and were
      monitored expectantly with scans every 3-4 months. Serum samples were obtained at
      weeks 1, 2, 3, 7, 9, 13, 19, 26, 50 and every 3 months. Antibody titers were
      monitored by ELISA and antibody binding to the cell surface of prostate cell
      lines was performed by flow cytometry. Complement-dependent cytotoxicity was
      performed on selected patients. Twenty evaluable patients were accrued to the
      study, of whom only one did not receive all six vaccinations. All patients
      developed maximum IgM and IgG antibody titers by week 9. The median IgM antibody
      titer by week 7 was 1/1,280 at 10 microg, 1/320 at 30 microg, 1/1,280 at 3 microg
      and 1/1,280 at 1 microg dose groups. The IgM titers from all groups remained
      greater than 1/320 by week 32 and beyond through week 50. We report here the
      results of a dose-escalating trial of a TF(c)-KLH conjugate vaccine in patients
      in the clinical state of a rising PSA in the absence of radiographic disease. For
      the first time, a synthetically made TF trimer or cluster (c) was made with three
      TF disaccharides attached to three sequential threonines on a peptide backbone.
      TF(c) doses of 1, 3, 10 and 30 microg were conjugated to KLH and administered
      with QS21. All doses induced high-titer IgM and IgG antibodies against TF. Unlike
      our findings in previous dose-escalating phase I trials, there did not appear to
      be increased antibody production with increasing doses of vaccine; higher titers
      of IgM and IgG antibodies developed at the lowest dose level (1 microg). An anti
      tumor effect in the form of a change in post-treatment versus pretreatment logPSA
      slopes was also observed. The results justify the inclusion of TF(c) at a dose of
      1 microg as a relevant antigenic target in a multivalent phase II vaccine trial
      in patients in the high-risk minimal disease state.

PMID- 15726363
TI  - Reduced-intensity conditioning followed by allografting of CD34-selected stem
      cells and < or =10(6)/kg T cells may have an adverse effect on transplant-related
      mortality.
AB  - In patients undergoing allogeneic peripheral blood stem cell (PBSC)
      transplantation after reduced-intensity conditioning (RIC), graft-versus-host
      disease (GVHD) represents a major cause of morbidity and mortality. T-cell
      depletion (TCD) prevents GVHD but carries potential risks of graft failure,
      opportunistic infections, and disease relapse. We explored ex vivo TCD of stem
      cell allografts that were administered after RIC treatment. Thirteen high-risk
      patients with hematological malignancies were treated with a
      fludarabine/melphalan-based RIC regimen followed by transplantation of
      immunomagnetically selected CD34(+) PBSC from HLA-identical sibling or matched
      unrelated donors. Patients were sequentially enrolled in two cohorts: group A
      (n=6) received antithymocyte globulin (ATG) during conditioning and 10(5) donor T
      cells/kg at transplantation, while group B (n=7) received 10(6) donor T cells/kg
      without ATG pretreatment. Primary graft failure occurred in two patients of group
      A and in one patient of group B. Complete donor chimerism persisting more than 1
      year was achieved in two cases per cohort. Acute grade II to IV or chronic
      extensive GVHD were observed in a total of six patients (group A, 2; group B, 4).
      Procedure-related deaths were mainly due to severe pneumonia occurring in two
      patients of group A and in five patients of group B. These results suggest that
      CD34 selection of reduced-intensity PBSC allografts may cause adverse effects
      upon specific antimicrobial immunity which can lead to fatal infections,
      particularly in high-risk patients. In our study, simultaneous add-back of < or
      =10(6)/kg donor T cells was unable to compensate for this deficiency.

PMID- 15726364
TI  - Inhibition by doxycycline of angiogenesis in the chicken chorioallantoic membrane
      (CAM).
AB  - Doxycycline, a tetracycline derivative, has many properties in addition to its
      antibiotic activity, including inhibition of matrix metalloproteinases (MMPs) and
      the ability to chelate divalent cations including Ca(2+). It has been shown to
      inhibit endothelial cell growth in vitro, and reduce the development of
      experimental tumours, especially bone metastasis in a model of breast cancer. We
      examined the effects of doxycycline on angiogenesis in the chicken
      chorioallantoic membrane (CAM) model, and showed that doxycycline will cause loss
      of the chorionic plexus in CAMs when applied at day 8 of incubation, and the
      duration of this inhibition was dose-dependent. Repeated doses prolonged the
      inhibition, but following removal of the doxycycline there was rapid recovery of
      the chorionic plexus. The effects of doxycycline are in part mimicked by the MMP
      inhibitor 1,10-phenanthroline, and more closely by the Ca(2+)-chelating agent
      EGTA. Doxycycline was equally effective in causing loss of the chorionic plexus
      by day 11 in CAMs, a time at which the blood vessels are established. Doxycycline
      has important potential as an antiangiogenic treatment. It is capable of
      inhibiting angiogenesis in an in vivo model, including the removal of
      comparatively mature endothelial cells. The response is sensitive to the dosing
      regimen and the effect is rapidly reversible.

PMID- 15726366
TI  - Pancratistatin causes early activation of caspase-3 and the flipping of
      phosphatidyl serine followed by rapid apoptosis specifically in human lymphoma
      cells.
AB  - Recently a major research effort has been focused on the development of
      anticancer drugs by targeting the components of a biochemical pathway to induce
      apoptosis in cancerous cells. Some of the natural products (e.g. paclitaxel) have
      been proven to be useful in inducing apoptosis in cancer cells with limited
      specificity. Pancratistatin, a natural product isolated and characterized over a
      decade ago, has been shown to be cytostatic and antineoplastic. We investigated
      the specificity and biochemical mechanism of action of pancratistatin.
      Pancratistatin seemed to show more specificity than VP-16 or paclitaxel as an
      efficient inducer of apoptosis in human lymphoma (Jurkat) cells, with minimal
      effect on normal nucleated blood cells. Caspase-3 activation and exposure of
      phosphatidyl serine on the outer leaflet of the plasma membrane were earlier
      events than the generation of ROS and DNA fragmentation observed following
      pancratistatin treatment. This indicates a possible involvement of caspase-3 and
      plasma membrane proteins in the induction phase of apoptosis. Our results
      indicate that pancratistatin does not cause DNA double-strand breaks or DNA
      damage prior to the execution phase of apoptosis in cancer cells. Parallel
      experimentation with VP-16, a currently used medication for cancer treatment,
      indicated that VP-16 causes substantial DNA damage in normal non-cancerous blood
      cells, while pancratistatin does not cause any DNA double-strand breaks or DNA
      damage in non-cancerous cells. Taken together, our finding that pancratistatin
      induces apoptosis in cancer cells using non-genomic targets, and more importantly
      does not seem to have any affect non-cancerous cells, presents a significant
      platform to develop non-toxic anticancer therapies.

PMID- 15726365
TI  - Therapeutic effect of tamoxifen and energy-modulating vitamins on carbohydrate
      metabolizing enzymes in breast cancer.
AB  - BACKGROUND: Cancer cells have an abnormal energetic metabolism. One of the
      earliest discovered hallmarks of cancer had its roots in bioenergetics, as many
      tumours were found in the 1920s to exhibit a high glycolytic phenotype. An animal
      with cancer shows significant and progressive energy loss from the host (i.e.
      noncancerous) tissues, which could occur by the establishment of a systemic
      energy-depriving cycle involving the interaction of tumour glycolysis and host
      gluconeogenesis. Tamoxifen (TAM) is a nonsteroidal antioestrogen that is widely
      used in adjuvant therapy for all stages of breast carcinoma. To improve the
      therapeutic efficacy of TAM and to expand its usage in the treatment of breast
      cancer, it is necessary to establish an energy-enhancing programme. In order to
      provide sufficient energy and to prevent cancer cachexia, TAM can be supplemented
      with energy-modulating vitamins (EMV). In this investigation the augmentation of
      the efficacy of TAM by the effects of EMV supplementation on carbohydrate
      metabolizing enzymes, the mitochondrial Krebs cycle and respiratory enzymes was
      evaluated in the mammary gland of carcinoma-bearing rats. METHODS: Female albino
      Sprague-Dawley rats were selected for the investigation. The experimental set-up
      included one control and four experimental groups. Mammary carcinoma was induced
      with 7,12- dimethyl benz(a)anthracene (25 mg), and TAM was administered orally
      (10 mg/kg body weight per day) along with EMV which comprised riboflavin (45
      mg/kg per day), niacin (100 mg/kg per day) and coenzyme Q(10) (40 mg/kg per day).
      RESULTS: Measurements were made on tumour tissue and surrounding normal tissue in
      all experimental groups. Tumour tissue showed significant (P<0.05) increases in
      the glycolytic enzymes hexokinase, phosphoglucoisomerase and aldolase, and
      significant decreases in the gluconeogenic enzymes glucose-6-phosphatase and
      fructose-1,6-biphosphatase. In contrast, the surrounding tissue showed
      significant decreases in glycolytic enzymes and significant increases in
      gluconeogenic enzymes. The activities of the mitochondrial Krebs cycle enzymes
      isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate
      dehydrogenase and malate dehydrogenase, and respiratory chain enzymes NADH
      dehydrogenase and cytochrome c oxidase were significantly reduced in both tumour
      and surrounding tissue of the mammary carcinoma-bearing rats. These biochemical
      disturbances were effectively counteracted by supplementation with EMV, which
      restored the activities of all these enzyme to their respective control levels.
      CONCLUSION: Combination therapy of TAM with EMV not only alters carbohydrate
      metabolism but can also prevent body weight loss by enhancing the host energy
      metabolism.

PMID- 15726367
TI  - Investigation of the role of Bax, p21/Waf1 and p53 as determinants of cellular
      responses in HCT116 colorectal cancer cells exposed to the novel cytotoxic
      ruthenium(II) organometallic agent, RM175.
AB  - Ruthenium(II) organometallic complexes form monofunctional adducts with guanine
      in DNA in vitro and have a cytotoxic anticancer activity spectrum in preclinical
      models suggesting lack of cross-resistance with cisplatin. The primary cytotoxic
      lesion remains to be identified but the downstream mechanism of action is
      nevertheless of interest. Using isogenic derivatives of the HCT116 colorectal
      cancer cell line, we investigated the role of p53, p21/WAF1 and Bax in the
      cellular response to the novel ruthenium(II) organometallic complex RM175,
      [(eta(6)-C(6)H(5)C(6)H(5))RuCl (H(2)NCH(2)CH(2)NH(2)-N,N')](+) PF(6)(-). Western
      blotting demonstrated dose-dependent accumulation of p53, Bax and p21/WAF1 within
      48 h of the start of RM175 treatment in wild-type HCT116 cells. HCT116 wild-type
      and Bax-null cells arrested in the G(1) and G(2) phases of the cell cycle. This
      pattern of cell cycle arrest was not observed in p53-null or in p21/WAF1-null
      cells. Following RM175 treatment, HCT116 wild-type and p21/WAF1 null cells
      underwent a dose-dependent induction of apoptosis (Annexin-V and sub-G(1)
      apoptosis assays). This apoptotic response was not observed in p53-null or Bax
      null cells. In short-term sulphorhodamine B assays, the IC(50) for RM175 was 16
      microM for p53-null HCT116, and 8 microM for wild-type cells (P<0.05). However,
      the sensitivity to RM175 in clonogenic assays at 16 days was independent of p53
      status. These results identify determinants of the short-term in vitro response
      to RM175 demonstrating a role for p53 and p21/WAF1 in the growth arrest and for
      p53 and Bax in the apoptotic response. The mechanism of p53-independent
      suppression of long-term clonogenicity remains to be determined.

PMID- 15726369
TI  - Effects of docetaxel on antigen presentation-related functions of human monocyte
      derived dendritic cells.
AB  - PURPOSE: Docetaxel (TXT) is a unique chemotherapeutic agent that has been
      approved for treating various types of malignancies. TXT stabilizes microtubule
      assembly in cells and causes various dysfunctions of microtubule-dependent
      cellular events. Patients with advanced malignancies are beginning to receive TXT
      in combination with immunotherapy; however, the influence of TXT at clinically
      achievable serum concentrations (less than 10(-6) M) on antigen presentation
      related functions of human monocyte-derived dendritic cells (Mo-DCs) remains
      unclear. METHODS: Immature Mo-DCs (imMo-DCs) were generated from peripheral blood
      monocytes with interleukin-4 and granulocyte-macrophage colony-stimulating factor
      in vitro. Mature Mo-DCs (mMo-DCs) were induced from imMo-DCs with tumor necrosis
      factor-alpha and prostaglandin E(2). RESULTS: TXT at concentrations lower than
      10(-7) M did not significantly affect cellular viability, phagocytosis, or
      expression of antigen presentation-related molecules of Mo-DCs. In contrast, TXT
      at concentrations lower than 10(-9) M significantly suppressed directional
      motility of imMo-DCs toward MIP-1alpha and of mMo-DCs toward MIP-3beta. However,
      TXT had no effect on either CCR1 expression by imMo-DCs or CCR7 expression by mMo
      DCs. No gross changes in the microtubule skeleton were evident by
      immunofluorescence microscopy after treatment with TXT at less than 10(-8) M.
      However, reduced numbers of imMo-DCs with podosomes localized primarily in one
      cell region were observed. CONCLUSIONS: The present results indicate that
      different concentrations of TXT influence antigen presentation-related functions
      differently. In particular, TXT at relatively low therapeutic doses disrupts
      chemotactic motility of Mo-DCs.

PMID- 15726368
TI  - Improvement of paclitaxel therapeutic index by derivatization and association to
      a cholesterol-rich microemulsion: in vitro and in vivo studies.
AB  - A cholesterol-rich microemulsion or nanoparticle termed LDE concentrates in
      cancer tissues after injection into the bloodstream. Here the cytotoxicity,
      pharmacokinetics, toxicity to animals and therapeutic action of a paclitaxel
      lipophilic derivative associated to LDE is compared with those of the commercial
      paclitaxel. Results show that LDE-paclitaxel oleate is stable. The cytostatic
      activity of the drug in the complex is diminished compared with the commercial
      paclitaxel due to the cytotoxicity of the vehicle Cremophor EL used in the
      commercial formulation. Competition experiments in neoplastic cultured cells show
      that paclitaxel oleate and LDE are internalized together by the LDL receptor
      pathway. LDE-paclitaxel oleate arrests the G(2)/M phase of cell cycle, similarly
      to commercial paclitaxel. Tolerability to mice is remarkable, such that the
      lethal dose (LD(50)) was ninefold greater than that of the commercial formulation
      (LD(50) = 326 microM and 37 microM, respectively). LDE concentrates paclitaxel
      oleate in the tumor roughly fourfold relative to the normal adjacent tissues. At
      equimolar doses, the association of paclitaxel oleate with LDE results in
      remarkable changes in the drug pharmacokinetic parameters when compared to
      commercial paclitaxel (t(1/2)=218 min and 184 min, AUC=1,334 microg h/ml and 707
      microg h/ml and CL=0.125 ml/min and 0.236 ml/min, respectively). Finally, the
      therapeutic efficacy of the complex is pronouncedly greater than that of the
      commercial paclitaxel, as indicated by the reduction in tumor growth, increase in
      survival rates and % cure of treated mice. In conclusion, LDE-paclitaxel oleate
      is a stable complex and compared with paclitaxel toxicity is considerably reduced
      and activity is enhanced, which may lead to improved therapeutic index in
      clinical use.

PMID- 15726370
TI  - A pharmacological study of celecoxib and gemcitabine in patients with advanced
      pancreatic cancer.
AB  - PURPOSE: To evaluate whether celecoxib alters the conversion of gemcitabine into
      its active metabolite, difluorodeoxycytidine triphosphate (dFdCTP), in peripheral
      blood mononuclear cells (PBMCs). METHODS: Patients with advanced pancreatic
      cancer who had not received chemotherapy and had acceptable organ function were
      eligible for the study. The initial dose of gemcitabine was 750 mg/m(2)
      administered intravenously at a rate of 10 mg/m(2)/min on days 1, 8, and 15 every
      4 weeks. Celecoxib was administered orally at 400 mg twice a day starting 2 days
      after the first dose of gemcitabine. Serial blood samples were taken during the
      first and second gemcitabine infusions and the cellular dFdCTP levels from PBMCs
      were analyzed. RESULTS: Five patients received gemcitabine at 750 mg/m(2) and six
      patients received it at 650 mg/m(2). Severe adverse events included neutropenia,
      thrombocytopenia, enteritis, and gastric perforation. Two patient died early
      during treatment. Cellular pharmacology studies showed that the conversion of
      gemcitabine into dFdCTP was not affected by celecoxib. CONCLUSION: Despite the
      increased clinical toxicities encountered with the combination, celecoxib did not
      alter the conversion of gemcitabine into its active metabolites in PBMCs.
      Gemcitabine 650 mg/m(2) infusion over 65 min on days 1, 8, and 15 every 4 weeks
      in combination with celecoxib at 400 mg twice a day was the dose recommended for
      further study.

PMID- 15726371
TI  - Pharmacokinetics of low-dose doxorubicin and metabolites in patients with AIDS
      related Kaposi sarcoma.
AB  - PURPOSE: Systemic chemotherapy is the treatment of choice for AIDS-related
      advanced Kaposi sarcoma. One principal schedule combines adriamycin
      (doxorubicin), bleomycin, and vincristine (ABV). We analysed the plasma
      concentrations of low-dose doxorubicin (Dx) and its metabolites doxorubicinol, 7
      deoxydoxorubicinone, doxorubicinone, doxorubicinolone, and 7
      deoxydoxorubicinolone in AIDS-patients to define patient-group and dose-specific
      pharmacokinetic parameters. MATERIALS AND METHODS: A previously described high
      performance liquid chromatographic (HPLC) method and a population approach with
      non-linear mixed effects modelling (NONMEM) were used for analysis and subsequent
      modelling of the time-concentration data of low-dose Dx and metabolites in seven
      patients with AIDS-related advanced Kaposi sarcoma. Patients received Dx 20 mg m(
      2), bleomycin 15 U m(-2) and vincristine 2 mg as a 30-min intravenous infusion
      each. Blood samples were collected up to 72 h after the start of Dx treatment.
      WinNonlin software version 4.1 was used for non-compartmental analysis and NONMEM
      software version V for compartmental analysis. Covariate analysis was performed
      for various clinical and laboratory parameters. RESULTS: Non-compartmental
      analysis yielded an area under the plasma concentration-time curve (AUC) for Dx
      of 566 mug h L(-1), a maximum plasma concentration (c(max)) of 599 mug L(-1) and
      an elimination half-life (t(1/2)) of 30.8 h. Compartmental analysis resulted in a
      two-compartment model with first-order elimination, which best fitted the
      concentration-time data. Model estimate for Dx clearance was 61.8 L h(-1), for
      intercompartmental clearance (Q) 112 L h(-1), for the volume of the central
      compartment (V(1)) 23.3 L, and for the volume of the peripheral compartment
      (V(2)) 1,130 L. Metabolite data could adequately be estimated by NONMEM using
      single-compartment models. Graphical plots of residuals versus time for all
      metabolites yielded no evidence of non-linear pharmacokinetic behaviour.
      Laboratory parameters of liver and renal function were all in the normal range
      and their inclusion in the pharmacokinetic model did not improve data fit. A
      final jack-knife analysis was performed. CONCLUSIONS: Concentration-time data for
      low-dose Dx and metabolites in the ABV-regimen are best described by a two
      compartment model with first-order elimination. The results confirm that the
      aglycones doxorubicinone, 7-deoxydoxorubicinone, and doxorubicinolone can be
      reliably detected in the studied patient group and implemented into a common
      metabolic model. Model estimates suggest that pharmacokinetic parameters are
      similar for low-dose Dx and higher-dosed Dx. As the role of the aglycones is
      still poorly understood, despite their potential clinical relevance, their
      analysis should be implemented in future pharmacokinetic and pharmacodynamic
      studies of Dx.

PMID- 15726372
TI  - First report of supraventricular tachycardia after intravenous pulse
      methylprednisolone therapy, with a brief review of the literature.
AB  - The occurrence of supraventricular tachycardia after high-dose intravenous
      methylprednisolone pulse therapy (HIVMPT) in a patient with active rheumatoid
      arthritis is described for the first time. This case report further expands the
      range of arrhythmias that can occur with HIVMPT. Other arrhythmias previously
      reported to occur after HIVMPT include atrial fibrillation, atrial flutter,
      junctional rhythm, and ventricular tachycardia. To the best of our knowledge,
      supraventricular tachycardia has not been reported previously, although severe
      bradycardia, hypotension, asystole, cardiovascular collapse, and sudden death
      have been documented. A review of the literature indicates that these case
      reports not withstanding, HIVMPT is generally safe, and cardiovascular toxicity
      is rare. However, close supervision with repeated measurements of blood pressure,
      electrocardiogram, and blood electrolytes is mandatory during and immediately
      after HIVMPT, especially for patients with pre-existing cardiovascular disease,
      and the lowest effective dose of methylprednisolone should be infused at a slow
      rate.

PMID- 15726374
TI  - Assessment of aortic stiffness and ventricular diastolic functions in patients
      with Behcet's disease.
AB  - BACKGROUND: Behcet's disease is a systemic vasculitis in which studies have given
      conflicting results about ventricular diastolic functions. However, tissue
      Doppler echocardiography has never been used in any of these studies. Aortic
      stiffness, a cardiovascular risk factor, may also precede ventricular
      dysfunction. OBJECTIVES: The aim of this study was to assess aortic stiffness and
      biventricular diastolic functions in patients with Behcet's disease. METHODS: A
      total of 26 patients with Behcet's disease (mean age; 33+/-10 years) and 20 age-
      and sex-matched controls (mean age; 33+/-7 years) were included. Aortic stiffness
      was evaluated by aortic strain and distensibility. Ventricular diastolic
      functions were evaluated with both conventional and tissue Doppler
      echocardiography. Mitral E and A wave, E/A ratio of E wave, deceleration time,
      and isovolumic relaxation time were calculated. RESULTS: There was no significant
      difference in diastolic Doppler parameters between patients and controls.
      Similarly, there was no significant difference in mitral annular E and A
      velocities between these two groups. Aortic strain in patients with Behcet's
      disease was found to be significantly less than in the controls (8.3+/-4.9% and
      15.7+/-2.7% respectively, p<0.001). Aortic distensibility was also significantly
      low in patients with Behcet's disease when compared to controls (0.45+/-0.28 and
      0.78+/-0.13 respectively, p<0.001). Beta index values were significantly high in
      Behcet's patients (7.23+/-5.93 and 2.69+/-0.55 respectively, p<0.001).
      CONCLUSION: No significant diastolic dysfunction was found in left and right
      ventricles in patients with Behcet's disease by using both conventional and
      tissue Doppler echocardiography. However, an increase in aortic stiffness was
      found, suggesting an inflammatory involvement of proximal aorta.

PMID- 15726373
TI  - Antibodies against cyclic citrullinated peptides in patients affected by
      rheumatoid arthritis before and after infliximab treatment.
AB  - To evaluate antibodies against cyclic citrullinated peptides (anti-CCP) together
      with rheumatoid factor (RF), antinuclear antibodies (ANA) and C-reactive protein
      (CRP), in patients affected by rheumatoid arthritis (RA), before and after
      infliximab treatment. Twenty-seven patients (five men and 22 women, mean age of
      51.9 years, mean duration of disease 12.6 years) affected by RA, refractory to
      conventional DMARDs, were treated with infliximab, at the conventional dosage.
      Before starting infliximab and after 22 weeks, on the occasion of the fifth
      infusion, anti-CCP antibodies were tested by ELISA method. At the same time IgM
      RF, ANA and CRP level were measured. Before infliximab therapy, anti-CCP
      antibodies resulted positive in 23 patients (85.1%); the serum level did not
      change after infliximab treatment; only one case negative at baseline became
      slightly positive after treatment. Before and after therapy RF resulted positive
      in 22 cases (81.4%) and 21 cases (77.7%) respectively; comparing values at
      baseline with those after 22 weeks of treatment with infliximab, RF levels
      significantly decreased, as well as CRP values. In contrast to both anti-CCP
      antibodies, which remained stable, and to RF, which fell after infliximab, ANA
      were positive > or = 1: 160 in four cases at baseline and in 12 after treatment.
      The titre of anti-CCP antibodies did not significantly change after anti-TNFalpha
      blocker administration; instead the positivity of RF significantly decreased. As
      opposed to antinuclear and anti-dsDNA antibodies, which may appear or increase in
      titre during infliximab treatment, the typical autoantibodies detectable in RA
      show a different trend; in fact, anti-CCP antibodies remained stable and RF
      decreased.

PMID- 15726375
TI  - Validation of a cotton-specific gene, Sad1, used as an endogenous reference gene
      in qualitative and real-time quantitative PCR detection of transgenic cottons.
AB  - Genetically modified (GM) cotton lines have been approved for commercialization
      and widely cultivated in many countries, especially in China. As a step towards
      the development of reliable qualitative and quantitative PCR methods for
      detecting GM cottons, we report here the validation of the cotton (Gossypium
      hirsutum) endogenous reference control gene, Sad1, using conventional and real
      time (RT)-PCR methods. Both methods were tested on 15 different G. hirsutum
      cultivars, and identical amplicons were obtained with all of them. No amplicons
      were observed when DNA samples from three species of genus Gossypium, Arabidopsis
      thaliana, maize, and soybean and others were used as amplified templates,
      demonstrating that these two systems are specific for the identification and
      quantification of G. hirsutum. The results of Southern blot analysis also showed
      that the Sad1 gene was two copies in these 15 different G. hirsutum cultivars.
      Furthermore, one multiplex RT-quantitative PCR employing this gene as an
      endogenous reference gene was designed to quantify the Cry1A(c) gene modified
      from Bacillus thuringiensis (Bt) in the insect-resistant cottons, such as Mon531
      and GK19. The quantification detection limit of the Cry1A(c) and Sad1 genes was
      as low as 10 pg of genomic DNA. These results indicate that the Sad1 gene can be
      used as an endogenous reference gene for both qualitative and quantitative PCR
      detection of GM cottons.

PMID- 15726376
TI  - Primitive mesenteric gastrointestinal stromal tumor with autonomic
      nerve/ganglionic differentiation presenting as a huge mass with small synchronous
      nodules.
AB  - We present a case of a primary mesenteric ectopic gastrointestinal stromal tumor.
      The pathologic characteristics of this neoplasm, autonomic nerve/ganglionic
      differentiation and presentation as a huge mass with small synchronous nodules,
      have not been previously described in the literature.

PMID- 15726378
TI  - Fetal cerebral biometry: normal parenchymal findings and ventricular size.
AB  - Assessing fetal cerebral biometry is one means of ascertaining that the
      development of the fetal central nervous system is normal. Norms have been
      established on large cohorts of fetuses by sonographic and neurofetopathological
      studies. Biometric standards have been established in MR in much smaller cohorts.
      The purpose of this paper is to analyse methods of measuring a few parameters in
      MR [biparietal diameter (BPD), fronto-occipital diameter (FOD), length of the
      corpus callosum (LCC), atrial diameter, transverse cerebellar diameter, height,
      anteroposterior diameter and surface of the vermis] and to compare US and MR in
      the assessment of fetal cerebral biometry.

PMID- 15726377
TI  - Radiological error: analysis, standard setting, targeted instruction and
      teamworking.
AB  - Diagnostic radiology does not have objective benchmarks for acceptable levels of
      missed diagnoses. Until now, data collection of radiological discrepancies has
      been very time consuming. The culture within the specialty did not encourage it.
      However, public concern about patient safety is increasing. There have been
      recent innovations in compiling radiological interpretive discrepancy rates which
      may facilitate radiological standard setting. However standard setting alone will
      not optimise radiologists' performance or patient safety. We must use these new
      techniques in radiological discrepancy detection to stimulate greater knowledge
      sharing, targeted instruction and teamworking among radiologists. Not all
      radiological discrepancies are errors. Radiological discrepancy programmes must
      not be abused as an instrument for discrediting individual radiologists.
      Discrepancy rates must not be distorted as a weapon in turf battles. Radiological
      errors may be due to many causes and are often multifactorial. A systems approach
      to radiological error is required. Meaningful analysis of radiological
      discrepancies and errors is challenging. Valid standard setting will take time.
      Meanwhile, we need to develop top-up training, mentoring and rehabilitation
      programmes.

PMID- 15726379
TI  - Evaluation of tumoral enhancement by superparamagnetic iron oxide particles:
      comparative studies with ferumoxtran and anionic iron oxide nanoparticles.
AB  - This study was designed to compare tumor enhancement by superparamagnetic iron
      oxide particles, using anionic iron oxide nanoparticles (AP) and ferumoxtran. In
      vitro, relaxometry and media with increasing complexity were used to assess the
      changes in r2 relaxivity due to cellular internalization. In vivo, 26 mice with
      subcutaneously implanted tumors were imaged for 24 h after injection of particles
      to describe kinetics of enhancement using T1 spin echo, T2 spin echo, and T2 fast
      spin echo sequences. In vitro, the r2 relaxivity decreased over time (0-4 h) when
      AP were uptaken by cells. The loss of r2 relaxivity was less pronounced with long
      (Hahn Echo) than short (Carr-Purcell-Meiboom-Gill) echo time sequences. In vivo,
      our results with ferumoxtran showed an early T2 peak (1 h), suggesting
      intravascular particles and a second peak in T1 (12 h), suggesting
      intrainterstitial accumulation of particles. With AP, the late peak (24 h)
      suggested an intracellular accumulation of particles. In vitro, anionic iron
      oxide nanoparticles are suitable for cellular labeling due to a high cellular
      uptake. Conversely, in vivo, ferumoxtran is suitable for passive targeting of
      tumors due to a favorable biodistribution.

PMID- 15726380
TI  - Right ventricular function late after total repair of tetralogy of Fallot.
AB  - Over the past decades, life expectancy in patients with congenital heart disease
      has increased dramatically. However, serious complications may develop late after
      total repair in infancy. These complications are usually the result of
      longstanding pulmonary regurgitation, which leads to dilatation of the right
      ventricle and an increased risk for severe arrhythmias. Therefore lifelong follow
      up in these patients is required. Cardiac magnetic resonance imaging is the
      current imaging tool of choice because it offers superior imaging quality and
      enables accurate quantification of functional parameters such as flow volumes and
      systolic and diastolic performance.

PMID- 15726381
TI  - Incidence of retro-aortic left renal vein and its relationship with varicocele.
AB  - The retro-aortic left renal vein (RLRV) is a malformation characterized by the
      presence of a vessel that drains the left renal blood up to the inferior vena
      cava crossing behind the aortic artery. Varicocele is defined as venous dilation
      of the pampiniform plexus, and the left side is the most commonly affected.
      Several theories concerning the possible aetiology of varicocele are reviewed in
      the literature, but RLRV was not mentioned as an aetiologic factor of varicocele.
      in this study we investigated the percentage of RLRVs and their relation with
      varicocele. A total of 1,125 contrast-enhanced abdominal CT scans was examined to
      identify RLRVs. RLRVs were found in nine women (1.6%) and ten men (1.7%). We
      performed scrotal Doppler ultrasonography (US) for all affected men except one.
      Varicocele of varying degrees was found in seven of the nine male patients with
      RLRV (77%). RLRV could be one of the aetiological factors in the development of
      varicocele, and the cases with RLRV should be examined by scrotal Doppler US for
      the presence of varicocele.

PMID- 15726382
TI  - Chemotherapy in metastatic renal cell cancer.
AB  - Currently, there is no standard treatment for patients with advanced renal cell
      carcinoma (RCC) who do not respond to or progress after transient remission to
      first-line immunotherapy. At the end of the 1990s, no single chemotherapeutic
      drug, alone or in combination with interleukin-2 (IL-2) or interferon-alfa (IFN),
      had shown activity beyond the one expected by immunotherapy alone. New drugs on
      the market such as the pyrimidine analog gemcitabine or taxane-based
      chemotherapeutics may show promising tumor activity in combination with targeted
      therapy, but this has to be substantiated in upcoming trials. There is a great
      need to develop effective systemic therapy for advanced MRCC and to evaluate the
      efficacy of new drugs in clinical trials.

PMID- 15726383
TI  - [Cyclosporine monitoring in patients with chronic uveitis].
AB  - BACKGROUND: Cyclosporine (CsA) is a widely used drug in the treatment of
      posterior uveitis. Whereas treatment with CsA has considerably improved the
      visual prognosis of uveitis patients, the therapeutic benefits of CsA are
      partially outweighed by its adverse effects, most notably nephrotoxicity and
      hypertension. Recently, monitoring the CsA 2-h postdose level (C(2)) has been
      recommended as the most sensitive assay and predictor of clinical outcome in
      transplantation. PATIENTS AND METHODS: This prospective clinical trial included
      15 patients with posterior uveitis who received oral CsA (5 mg/kg BW b.i.d.). The
      relationship of C(2) to C0 blood levels was analyzed and correlated with clinical
      safety and efficacy. RESULTS: A high intrapatient and interpatient variability
      was observed regarding the C0 values depending on several factors including
      comedication and intestinal resorption. C(2) values corresponded to control
      measurements of intraocular inflammation. CONCLUSIONS: C(2) monitoring offers a
      simple and accurate alternative for clinical monitoring of CsA. It allows the
      dose of CsA to be individualized effectively for each patient.

PMID- 15726384
TI  - The role of nitric oxide in the regulation of the systemic and pulmonary
      vasculature of the rattlesnake, Crotalus durissus terrificus.
AB  - The functional role of nitric oxide (NO) was investigated in the systemic and
      pulmonary circulations of the South American rattlesnake, Crotalus durissus
      terrificus. Bolus, intra-arterial injections of the NO donor, sodium
      nitroprusside (SNP) caused a significant systemic vasodilatation resulting in a
      reduction in systemic resistance (Rsys). This response was accompanied by a
      significant decrease in systemic pressure and a rise in systemic blood flow.
      Pulmonary resistance (Rpul) remained constant while pulmonary pressure (Ppul) and
      pulmonary blood flow (Qpul) decreased. Injection of L-Arginine (L-Arg) produced a
      similar response to SNP in the systemic circulation, inducing an immediate
      systemic vasodilatation, while Rpul was unaffected. Blockade of NO synthesis via
      the nitric oxide synthase inhibitor, L-NAME, did not affect haemodynamic
      variables in the systemic circulation, indicating a small contribution of NO to
      the basal regulation of systemic vascular resistance. Similarly, Rpul and Qpul
      remained unchanged, although there was a significant rise in Ppul. Via injection
      of SNP, this study clearly demonstrates that NO causes a systemic vasodilatation
      in the rattlesnake, indicating that NO may contribute in the regulation of
      systemic vascular resistance. In contrast, the pulmonary vasculature seems far
      less responsive to NO.

PMID- 15726386
TI  - Sodium pump molecular activity and membrane lipid composition in two disparate
      ectotherms, and comparison with endotherms.
AB  - Previous research has shown that the lower sodium pump molecular activity
      observed in tissues of ectotherms compared to endotherms, is largely related to
      the lower levels of polyunsaturates and higher levels of monounsaturates found in
      the cell membranes of ectotherms. Marine-based ectotherms, however, have very
      polyunsaturated membranes, and in the current study, we measured molecular
      activity and membrane lipid composition in tissues of two disparate ectothermic
      species, the octopus (Octopus vulgaris) and the bearded dragon lizard (Pogona
      vitticeps), to determine whether the high level of membrane polyunsaturation
      generally observed in marine-based ectotherms is associated with an increased
      sodium pump molecular activity relative to other ectotherms. Phospholipids from
      all tissues of the octopus were highly polyunsaturated and contained high
      concentrations of the omega-3 polyunsaturate, docosahexaenoic acid (22:6 (n-3)).
      In contrast, phospholipids from bearded dragon tissues contained higher
      proportions of monounsaturates and lower proportions of polyunsaturates. Sodium
      pump molecular activity was only moderately elevated in tissues of the octopus
      compared to the bearded dragon, despite the much greater level of
      polyunsaturation in octopus membranes. When the current data were combined with
      data for the ectothermic cane toad, a significant (P = 0.003) correlation was
      observed between sodium pump molecular activity and the content of 22:6 (n-3) in
      the surrounding membrane. These results are discussed in relation to recent work
      which shows a similar relationship in endotherms.

PMID- 15726385
TI  - Seasonal variations in circadian rhythms coincide with a phase of sensitivity to
      short photoperiods in the European hamster.
AB  - European hamsters (Cricetus cricetus) show pronounced seasonal changes in their
      physiology and behavior. The present study provides a detailed analysis of the
      temporal relationship between seasonal cycles of reproduction and body mass and
      seasonal changes of two circadian parameters, i.e., locomotor activity and 6
      sulphatoxymelatonin (aMT6s) excretion, in individual animals kept under natural
      light conditions. Our results demonstrate a characteristic pattern of locomotor
      activity and aMT6s excretion observed around the summer solstice, i.e., from mid
      May to mid-July. During this time, locomotor activity was characterized by a high
      level of activity and an early activity onset, while the nightly elevation of
      melatonin was reduced to baseline levels. These seasonal changes in aMT6s
      excretion and locomotor activity were only loosely related to changes in the
      reproductive status of the animals, but correlated well with a period of the
      annual cycle during which the animals were sensitive to short days. They may
      therefore reflect a specific state of the circadian pacemaker system within the
      SCN and can thus be a valuable tool to further characterize molecular and
      physiological mechanisms of photoperiodic time measurements in European hamsters.

PMID- 15726387
TI  - Age-related changes in lateral ventricle morphology in craniosynostotic rabbits
      using magnetic resonance imaging.
AB  - BACKGROUND AND AIMS: Craniosynostosis occurs in 300-500 per 1,000,000 live births
      and results in secondary craniofacial, ocular, and intracranial anomalies.
      Neurologic problems associated with craniosynostosis include changes in
      intracranial morphology such as dilation of the cerebral ventricles, however,
      clinical studies are confounded by small sample sizes, heterogenous samples, and
      lack of age-matched controls. The present study was designed to assess age
      related changes in the lateral ventricle volume of the brain in normal rabbits
      and rabbits with naturally-occurring coronal suture synostosis using serial
      magnetic resonance imaging. METHODS: Eighteen rabbits (6 wild-type controls, 6
      with early-onset [ approximately 21 days gestation], and 6 with delayed-onset
      [approximately 25 days post-gestation] coronal suture synostosis) had magnetic
      resonance imaging (MRI) at 10, 25, and 42 days of age. RESULTS: The results
      demonstrate that rabbits with early-onset synostosis had significantly (p<0.001)
      dilated and larger lateral ventricles (by 77% at 10 days of age) than wild-type
      and delayed-onset synostosis rabbits, which progressively worsened by day 42.
      CONCLUSION: This finding suggests that uncorrected coronal suture synostosis may
      have early effects on lateral ventricle volume hypertrophy, possibly through
      obstructed cerebrospinal fluid and/or venous drainage and circulation.

PMID- 15726389
TI  - Pitfalls in the management of newborn cloacas.
AB  - Clinicians caring for newborns with persistent cloaca face significant challenges
      in the newborn period. Avoiding key pitfalls during this time can have dramatic
      implications. We reviewed the medical records of 361 patients with cloaca
      operated on at our institution and analyzed sequelae that resulted from incorrect
      management in the newborn period. Of 361 patients, 282 underwent primary
      operations at our institution, and 79 patients were referred to us after a failed
      repair at other institutions. Pitfalls in management during the newborn period
      included the following: (1) Failure to recognize and manage hydrocolpos, which
      occurred in 46 patients. Of these, three patients developed pyocolpos (two
      progressed to vaginal perforation), and 43 suffered from persistent bilateral
      hydronephrosis, megaureters, recurrent urinary tract infections, persistent
      acidosis, or failure to thrive due to undrained hydrocolpos. They underwent
      unnecessary urinary drainage procedures (nephrostomy, ureterostomy, cystostomy,
      or vesicostomy) in the newborn period. When the vagina was finally decompressed,
      all of these symptoms disappeared. (2) Colostomy or vesicostomy problems, which
      occurred in 50 patients. These included incorrect placement of the colostomy (too
      distal, which interfered with the pull-through) in 24 and colostomy prolapse in
      23. Incompletely diverting loop colostomies led to urinary tract infections in 49
      patients. Vesicostomy prolapse occurred in three patients. (3) Clinical
      misdiagnosis, which occurred in 42 patients. Six were incorrectly diagnosed as
      "intersex" and 36 as "rectovaginal fistula." In this group only the rectum was
      repaired, and the patients were left with a urogenital sinus that required
      reoperation. Proper management of a newborn with cloaca includes drainage of a
      hydrocolpos, which avoids unnecessary urinary diversions and pyocolpos. Our
      preferred colostomy is one with separated stomas, adequate distal bowel for the
      pull-through, and use of a proper technique to avoid prolapse. Correct clinical
      diagnosis of cloaca avoids problems during the definitive repair.

PMID- 15726388
TI  - Germ cell development in the descended and cryptorchid testis and the effects of
      hormonal manipulation.
AB  - Germ cell development is an active process in normal testes during the first 4
      years after birth, with transformation of the neonatal gonocytes into adult dark
      spermatogonia and then primary spermatocytes. The hormonal regulation of these
      changes is not fully understood, with evidence both for and against a role for
      gonadotrophins and androgens. Early surgical intervention in infancy aims to
      prevent or reverse germ cell maldevelopment. Although hormonal treatment for
      maldescent has been shown to be ineffective, there is still controversy over
      whether it may be useful as an adjunct to surgery to stimulate germ cells.
      Current evidence suggests that hormonal therapy may not stimulate transformation
      of neonatal gonocytes but may trigger prepubertal mitosis of primary
      spermatocytes. Further studies are required to determine the role of hormone
      treatment on germ cell development.

PMID- 15726390
TI  - Mesalazine-induced myopericarditis in a patient with ulcerative colitis.

PMID- 15726391
TI  - Protective effects of (-)-epicatechin-3-gallate on UVA-induced damage in HaCaT
      keratinocytes.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been
      extensively studied and shown to be a powerful antioxidant protecting skin cells
      against photodamage. In this study, however, we demonstrated that another
      gallated catechin, (-)-epicatechin-3-gallate (ECG), was also able to protect
      human keratinocytes against damage induced by ultraviolet A (UVA) light. We found
      that ECG dose-dependently inhibited UVA-induced keratinocyte death as determined
      by cell viability assay. Moreover, ECG had similar potency to EGCG in inhibiting
      UVA-induced cell death. Therefore, the mechanism of action of ECG was further
      investigated. As assayed by flow cytometry, UVA-induced hydrogen peroxide (H2O2)
      production in keratinocytes was inhibited by ECG in a concentration-dependent
      manner, suggesting that ECG can act as a free radical scavenger while
      keratinocytes were photodamaged. The scavenging effect of ECG was confirmed by
      the fact that ECG treatment attenuated cell damage induced by H2O2 and
      hypoxanthine-xanthine oxidase. In a parallel experiment, UVA-induced activation
      of extracellular signal-regulated kinase in keratinocytes was blocked by ECG. We
      provided here the first evidence that ECG is a potent protectant that protects
      keratinocytes from photodamage. Because ECG is abundant in green tea, we believe
      that this compound is beneficial for skin care.

PMID- 15726392
TI  - Effects of working permanent night shifts and two shifts on cognitive and
      psychomotor performance.
AB  - OBJECTIVES: The study aimed to clarify whether cognitive and psychomotor
      performance, which are important for occupational and traffic safety, are
      impaired by working permanent night shifts (NSs) compared with early-late two
      shifts (TSs) and whether age and chronobiological type influences the
      relationship between shift and performance. METHODS: The study included 44 male
      automobile workers, 20 working TSs and 24 working NSs. Chronobiological type was
      determined by questionnaire (D-MEQ). Each subject was tested at the beginning and
      end of the shift for alertness [by a visual analogue scale (VAS)]; feeling of
      well-being (Basler); concentration and accuracy (d2); reaction speed, orientation
      and reaction to stress (Vienna System). RESULTS: TS workers were more frequently
      morning types whereas the NS workers were more frequently evening types. In the
      performance tests, the TS and NS workers did not differ at shift start or shift
      end. Over the course of the shift, concentration and accuracy improved in both
      groups, as did reaction to stress. Chronobiological type alone or in combination
      with shift type had no effect on performance. CONCLUSIONS: The results of this
      study indicate that-if chosen voluntarily-working NSs has no immediate negative
      effects on cognitive and psychomotor performance when compared with working TSs.
      There was no indication of an increased risk of accidents after working NSs. The
      unequal distribution of the circadian types in the shift groups may indicate
      selection.

PMID- 15726394
TI  - Overcommitment to work is associated with vital exhaustion.
AB  - OBJECTIVES: Vital exhaustion has been shown to predict the progression and
      manifestation of cardiovascular disease. Little is known about the relationship
      between vital exhaustion and overcommitment, the inability to withdraw from
      obligations at work. The aim of this study was to explore the relationship
      between vital exhaustion and overcommitment at work, as measured by the intrinsic
      effort scale of the effort-reward model after consideration of other potentially
      salutogenetic and pathogenetic working conditions. METHODS: This cross-sectional
      study is based on a stratified random sample of 634 employees (mean age 39.9
      years, standard deviation 10.7 years) from a manufacturing and assembly plant for
      aeroplane parts. Participants completed a questionnaire, which included the nine
      item shortened Maastricht exhaustion questionnaire to score the dependent
      variable exhaustion, and the six-item short form of the intrinsic-effort scale
      ("immersion") of the effort-reward-imbalance model as the primary independent
      variable. Perceived work stress was assessed by Siegrist's effort-reward
      imbalance questionnaire and the 52-item, 13 subscale salutogenetic subjective
      work assessment (SALSA) questionnaire, which focuses on indicators of perceived
      work stress in terms of pathogenetic and salutogenetic descriptors of decision
      latitude, psychological job demands, and social support. Additional candidate
      covariates included depression, anxiety and type-D personality. RESULTS: In
      regression analysis, overcommitment (r=0.516; P<0.0001) was independently
      associated with vital exhaustion. Multivariable linear regression analysis showed
      that overcommitment explained 27% of the variance of vital exhaustion.
      CONCLUSIONS: Overcommitment, indicating an exhaustive work-related coping style,
      is independently associated with vital exhaustion. It appears to be an important
      personality trait that may contribute to feelings of exhaustion at times of
      increased job strain.

PMID- 15726393
TI  - Airways symptoms, immunological response and exposure in powder painting.
AB  - OBJECTIVES: Powder painting is an alternative to solvent-based spray painting.
      Powder paints may contain organic acid anhydrides (OAAs), which are irritants to
      the airways and may cause sensitisation. The aim of this study was to determine
      the prevalence of respiratory symptoms and immunological response among powder
      painters and to describe the exposure to OAAs. METHODS: In all, 205 subjects in
      32 enterprises participated: 93 exposed and 26 formerly exposed workers in 25
      powder paint shops and 86 unexposed workers. They completed a questionnaire about
      working conditions and symptoms and took part in a medical examination, which
      included a lung function test. Urine samples, for determination of two OAAs, and
      blood samples, for analysis of specific antibodies against the OAAs, were taken.
      In addition, 33 paint samples were analysed for nine OAAs. RESULTS: The powder
      painters reported more work-related respiratory symptoms than unexposed subjects
      did. The prevalence of three or more symptoms was 24% in subjects with low
      exposure, 44% in highly exposed individuals, 46% in formerly exposed subjects and
      19% in unexposed workers. Asthma symptoms were frequent, 7%, 40%, 15% and 2%,
      respectively. Regression analyses of the lung volumes did not show any influence
      of exposure. IgG, but not IgE, against the OAAs and metabolites of OAAs was found
      in some subjects, but no associations with the exposure could be observed. OAAs
      were found in only small amounts in the paint samples. CONCLUSIONS: The exposure
      to organic acid anhydrides was estimated to be low, and yet, IgG antibodies to
      OAA were observed in some subjects. The prevalence of work-related symptoms from
      the eyes and the airways was relatively high among the powder painters, and these
      symptoms, but not the lung volumes, were clearly related to exposure. The
      symptoms were probably caused by irritative properties of the powder paint dust.

PMID- 15726395
TI  - Traffic air pollution and hospital admission for asthma: a case-control approach
      in a Turin (Italy) population.
AB  - OBJECTIVES: This study investigated the relationship between traffic air
      pollution and asthma, using a case-control design applied to routinely collected
      data. METHODS: Subjects resident in Turin during the period 1997-1999 and
      admitted for asthma were defined as cases; patients admitted for causes other
      than respiratory diseases or heart diseases were defined as controls. Nitrogen
      dioxide and total suspended particulate were considered as indicators of traffic
      air pollution. Statistical analysis were performed, separately for young (0-14
      years), adult (15-64 years) and elderly (>64 years) patients, with a logistic
      regression model; results are expressed as percentage of risk modification for a
      10 g/m(3) increase in exposure to pollutants. RESULTS: The risk of emergency
      admissions for asthma rose significantly with increased exposure to nitrogen
      dioxide [2.4%, 95% Confidence Interval: 0.5%; 4.3%], and total suspended
      particulate [2.3%, 95% Confidence Interval: 1.1%-3.6%]. The significant
      association was evident, in particular, among young and elderly patients for both
      pollutants. CONCLUSION: Using a case-control design both easy to use and manage,
      the study confirms the significant association between hospital emergency
      admissions for asthma and exposure to nitrogen dioxide and total suspended
      particulate pollutants.

PMID- 15726397
TI  - 145 years of Langenbeck's Archives: the oldest journal worldwide in scientific
      surgery.

PMID- 15726396
TI  - Genotoxic risk assessment in white blood cells of occupationally exposed workers
      before and after alteration of the polycyclic aromatic hydrocarbon (PAH) profile
      in the production material: comparison with PAH air and urinary metabolite
      levels.
AB  - OBJECTIVE: Workers in various industries can be exposed to polycyclic aromatic
      hydrocarbons (PAHs). The relationship between biomarkers of genotoxic risk, PAH
      compounds in air (ambient monitoring) and PAH metabolites in urine (internal
      exposure) were studied in 17 workers exposed to PAHs in a fireproof-material
      producing plant before and 3 months after the PAH profile was altered in the
      binding pitch. METHODS: Two biomarkers of exposure, specific DNA adducts of (+/-)
      r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) and
      non-specific DNA adduct of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were
      determined in white blood cells (WBCs). In addition, DNA strand breaks were
      analysed in lymphocytes by single-cell gel electrophoresis in a genotoxic risk
      assessment. Sixteen PAH compounds in air were determined by personal air
      sampling, and hydroxylated metabolites of phenanthrene, pyrene and naphthalene
      were determined in urine. RESULTS: After substitution of the binding pitch the
      concentrations of benzo[a]pyrene in air decreased (P<0.01). No changes could be
      observed for pyrene, while levels of phenanthrene (P=0.0013) and naphthalene
      (P=0.0346) in air increased. Consequently, median DNA adduct rates of anti-BPDE
      decreased after alteration of the production material (from 0.9 to <0.5
      adducts/10(8) nucleotides). No changes in the excretion of 1-hydroxypyrene in
      urine could be determined, whereas increased levels of 1-, 2+9-, 3- and 4
      hydroxyphenanthrene (P<0.0001) and 1-naphthol and 2-naphthol (P=0.0072) were
      found in urine. In addition, a statistically significant increase in DNA strand
      break frequencies (P<0.01) and elevated 8-oxodGuo adduct levels (P=0.7819, not
      statistically significant) were found in the WBCs of exposed workers 3 months
      after the PAH profile in the binding pitch had been altered. CONCLUSION: The
      results presented here show that the increased concentration of naphthalene
      and/or phenanthrene in the air at the work place could induce the formation of
      DNA strand breaks and alkali-labile sites in WBCs of exposed workers.

PMID- 15726398
TI  - The Study Centre of the German Surgical Society--rationale and current status.
AB  - BACKGROUND: The concept of evidence-based medicine was introduced into surgery in
      the mid-1990s, initially focussing on the integration of best research evidence,
      surgeons' expertise and patients' value. The lack of relevant external evidence
      [randomised controlled trials (RCTs), systematic reviews] in favour of surgical
      procedures has led to the need for a new approach in clinical research. DESIGN:
      Development and implementation of the Study Centre of the German Surgical Society
      (SDGC) in order to design, perform and analyse multicentre randomised controlled
      trials in surgery. RESULTS: The German Surgical Society has recently initiated
      four surgical RCTs within the SDGC in order to improve the national
      infrastructure for clinical research and its international scientific standing.
      All surgical trials focus on procedures in various fields (thyroid and
      parathyroid diseases, pancreatic surgery, abdominal wall closure) and are
      designed to fit the specific needs of each study (blinding of patients and
      assessors, ranking of endpoints, patients' perspective). Additionally, in a
      nationwide survey of 1,274 surgical departments in Germany, 307 replied, of which
      237 (19%) were willing to participate in multicentre projects. CONCLUSION:
      Evidence-based medicine has changed surgical practice, leading to an increase in
      demand for RCTs and requiring a new infrastructure in surgical departments and
      scientific societies.

PMID- 15726399
TI  - Predictive value of intact parathyroid hormone measurement during surgery for
      renal hyperparathyroidism.
AB  - BACKGROUND AND AIMS: In contrast to that in patients with primary
      hyperparathyroidism, the value of intraoperative intact parathyroid hormone
      (iPTH) measurement is still unclear in patients with renal hyperparathyroidism
      and was, therefore, evaluated in a large cohort of patients. PATIENTS:
      Intraoperative iPTH measurement was performed in 153 patients with renal
      hyperparathyroidism (129 with terminal renal failure and 24 with functioning
      kidney graft). Subtotal and total parathyroidectomy were performed in 123 and 13
      patients, respectively, during initial surgery. In patients with recurrent
      disease (17), the respective hyperfunctioning tissue was removed. Intraoperative
      blood samples were obtained by puncture of the internal jugular vein before
      preparation of the parathyroids (PTH0) and 15 min after parathyroidectomy
      (PTH15). iPTH was measured with the Elecsys 2010 system. Postoperative iPTH
      levels (PTH(post)) were determined at postoperative days 1 to 3 and at week 2.
      Patients were arbitrarily divided in four groups according to the postoperative
      iPTH values: 0-25 pg/ml (group 1), 26-65 pg/ml (group 2), 66-150 pg/ml (group 3)
      and more than 150 pg/ml (group 4). RESULTS: The mean PTH0 value was 869+/-57
      pg/ml, which decreased to 167+/-15 pg/ml at PTH15. The mean relative PTH15 value
      was 21.6+/-1.7%. Postoperatively, iPTH decreased to 42+/-9 pg/ml. The
      postoperative iPTH value of the 129 patients with terminal renal failure was 25
      pg/ml or less in 99 patients, 26-65 pg/ml in 11 patients, 66-150 pg/ml in eight
      patients and higher than 150 pg/ml in 11 patients. Two successive criteria of
      iPTH decrease were used: first, a PTH15 of < or =150 pg/ml or, second, a relative
      PTH15 of < or =30% less was used. Fifteen patients did not fulfil both criteria.
      In 13 of them (86.7%) iPTH(post) was higher than 65 pg (true failure to decline).
      Of 114 patients who fulfilled the criteria, 108 (94.7%) had normal postoperative
      iPTH values (true decline). Absolute PTH15 values of less than 150 pg/ml
      predicted normal postoperative iPTH levels in 77 of 78 patients. CONCLUSION: A
      PTH15 value of 150 pg/ml or less predicts operative success in patients with
      renal failure in 98.7% of cases, independently of the relative decay. In
      contrast, if the relative PTH15 is higher than 30%, high postoperative PTH values
      are predicted with a probability of 86.7%. Although there remain some borderline
      cases, intraoperative iPTH measurement is accurate and also can be useful in
      patients with renal hyperparathyroidism.

PMID- 15726400
TI  - Apoptosis by gemcitabine in non-small cell lung cancer cell line KNS62 is induced
      downstream of caspase 8 and is profoundly blocked by Bcl-xL over-expression.
AB  - BACKGROUND: This study assesses the chemotherapeutic drug gemcitabine in the
      human non-small cell lung cancer (NSCLC) cell line KNS62 in relation to the CD95
      induced apoptotic pathway, and the role of the anti-apoptotic protein Bcl-xL in
      vitro and in vivo. MATERIALS AND METHODS: Apoptosis was determined by JAM assay
      and DAPI staining analysis. Activation of key apoptotic proteins, including
      caspases 3, 8 and 9 and BID, as well as cytochrome c release and mitochondrial
      transmembrane potential (MTP), were measured. The impact of the caspase inhibitor
      zVAD on gemcitabine-induced apoptosis was quantified. The in vitro results were
      verified in vivo in an orthotopic murine xenotransplantation model. RESULTS:
      Gemcitabine treatment, as well as stimulation of CD95, resulted in cleavage of
      effector caspase 3 as well as its substrate PARP and caspase 9, followed by DNA
      fragmentation. Cleavage of caspase 8 was demonstrated after CD95 activation but
      not after the application of gemcitabine. In KNS62-Bcl-xL clones, release of
      cytochrome c and loss of mitochondrial transmembrane potential were suppressed.
      Consequently, apoptosis after gemcitabine therapy, as well as CD95-induced
      apoptosis, were significantly inhibited. Caspase inhibitor zVAD only partly
      reversed gemcitabine-induced DNA fragmentation. In vivo, there was a significant
      reduction in tumour volume under gemcitabine therapy. Bcl-xL over-expressing
      tumours were completely resistant to gemcitabine therapy. CONCLUSIONS: In NSCLC
      cell line KNS62 gemcitabine activated the mitochondrial apoptotic pathway
      downstream of mitochondria without activation of initiator caspases. Bcl-xL over
      expression induced significant resistance to gemcitabine. In vivo, the anti
      apoptotic effect of Bcl-xL was more pronounced than in vitro. Gemcitabine also
      induced caspase-independent DNA fragmentation in KNS62 cells.

PMID- 15726401
TI  - BiP and zein binding domains within the delta zein protein.
AB  - Zeins are alcohol soluble seed storage proteins synthesized within the endosperm
      of maize and subsequently deposited into endoplasmic reticulum (ER) derived
      protein bodies. The genes encoding the beta and delta zeins were previously
      introduced into tobacco with the expectation of improving the nutritional quality
      of plants (Bagga et al. in Plant Physiol 107:13, 1997). Novel protein bodies are
      produced in the leaves of transgenic plants accumulating the beta or delta zein
      proteins. The mechanism of protein body formation within leaves is unknown. It is
      also unknown how zeins are retained in the ER since they do not contain known ER
      retention motifs. Retention may be due to an interaction of zeins with an ER
      chaperone such as binding luminal protein (BiP). We have demonstrated protein
      protein interactions with the delta zeins, beta zeins, and BiP proteins using an
      E. coli two-hybrid system. In this study, four putative BiP binding motifs were
      identified within the delta zein protein using a BiP scoring program (Blond
      Elguindi et al. in Cell 75:717, 1993). These putative binding motifs were mutated
      and their effects on protein interactions were analyzed in both a prokaryotic two
      hybrid system and in plants. These mutations resulted in reduced BiP-zein protein
      interaction and also altered zein-zein interactions. Our results indicate that
      specific motifs are necessary for BiP-delta zein protein interactions and that
      there are specific motifs which are necessary for zein-zein interactions.
      Furthermore, our data demonstrates that zein proteins must be able to interact
      with BiP and zeins for their stability and ability to form protein bodies.

PMID- 15726402
TI  - Simultaneous tumour-like, atypical basal cell hyperplasia and acinar
      adenocarcinoma of the prostate: a comparative morphological and genetic approach.
AB  - Basal cell tumours of the prostatic gland are rare, and the classification is
      difficult. In the present case report, a large, tumour-like proliferation of
      atypical basaloid cells was found incidentally in a prostatectomy specimen that
      otherwise contained a conventional acinar adenocarcinoma. The basaloid cells
      displayed a solid or adenoid-cystic growth pattern and strongly expressed high
      molecular-weight cytokeratins and bcl-2. A high Ki-67 index was recorded within
      the atypical basaloid cells, by far exceeding the one counted in the conventional
      adenocarcinoma. However, there were no definite criteria for a malignant
      behaviour of the basal cell tumour. Comparative genomic hybridisation from
      microdissected tumour cells yielded losses at the short arms of chromosomes 8 and
      12 in the conventional adenocarcinoma and a normal karyotype in the basal cell
      tumour. The pathological findings favoured the diagnosis of an atypical basal
      cell hyperplasia.

PMID- 15726403
TI  - Rhabdomyomatous mesenchymal hamartoma of oral cavity: an unusual location for
      such a rare lesion.

PMID- 15726404
TI  - Basaloid carcinoma of the pancreas.
AB  - A case of basaloid carcinoma of the pancreas in a 26-year-old woman is reported.
      The tumour was constituted by solid nests of relatively uniform neoplastic cells
      with hyperchromatic nuclei and scant cytoplasm, showing distinct peripheral
      palisading. There were necrotic areas and deposition of hyaline material,
      suggesting a basement membrane-like substance. Small foci of clear-cut squamous
      differentiation were present. Tumour cells were positive for cytokeratin 14 and
      P63 and negative for neuroendocrine and acinic cell markers. Ultrastructurally,
      the tumour was constituted by polygonal cells with round nuclei containing
      clumped chromatin. Occasional tight junctions and keratin filaments were present.
      Basaloid carcinomas may arise in several sites of the body, the most frequent
      being the anus and oesophagus, and have poor clinical outcome. The present case
      appears to be, to the best of our knowledge, the first documented example in the
      literature of basaloid carcinoma of the pancreas.

PMID- 15726405
TI  - Pleomorphic variant of invasive lobular carcinoma of the male breast.

PMID- 15726406
TI  - A case of idiopathic sclerosing mediastinitis in a 7-year-old Japanese boy.
AB  - Sclerosing mediastinitis is a very rare benign disorder characterised by the
      development of dense fibrous tissue within the mediastinum. Affected patients are
      typically young adults with infant cases being uncommon especially in areas
      without endemic histoplasmosis. We report a Japanese boy with markedly elevated
      serum inflammatory markers for more than 1 year in the absence of any clinical
      manifestations. 67Ga-scintigraphy demonstrated an accumulation in the mediastinal
      region and an open biopsy revealed a hard fibrous mass in the anteriosuperior
      mediastinum. Thus, a diagnosis of idiopathic sclerosing mediastinitis was made.
      CONCLUSION: To the best of our knowledge, this case is the youngest patient
      reported with this disorder. In patients with mediastinal mass lesions the
      diagnosis of sclerosing mediastinitis should be considered as well as infectious,
      autoimmune or neoplastic disease even in children.

PMID- 15726409
TI  - What the paediatricians need--the launch of paediatric research in Europe.
AB  - Most parents and many paediatricians are not aware that medicines for children
      are often not tested, labelled, or approved for their prescribed use. In 1997,
      the Food and Drug Administration developed incentives for pharmaceutical
      companies to perform paediatric research in medications. The European Commission
      brought out its proposal for paediatric incentives after in-depth internal
      reflection. Now it should be adapted quickly to boost pharmaceutical paediatric
      research in the EU as soon as possible. CONCLUSION: The proposal must be balanced
      and aware that both incentives and requirements are mandatory in order to
      maintain and stimulate paediatric research on medicines in Europe.

PMID- 15726408
TI  - Tight skin and limited joint movements as early presentation of Hutchinson
      Gilford progeria in a 7-week-old infant.
AB  - We present a 7-week-old male infant with pseudoscleroderma as a primary
      manifestation of the Hutchinson-Gilford syndrome of premature aging. He had
      suffered intra-uterine growth retardation; micrognathism and a cleft palate were
      evident at birth. He presented with feeding difficulties and severe, diffuse
      scleroderma-like lesions, a faint peri-oral cyanosis and prominent scalp veins.
      With time, special facial features became more and more apparent: frontal
      bossing, prominent eyes, thin and fine nose and lips, microstomia, low-set ears
      and occipito-parietal alopecia. Histopathology of the skin showed an increased
      density and thickness of collagen in the dermis and hypodermis. Within the 1st
      year of life, typical skeletal characteristics were observed. The diagnosis of
      Hutchinson-Gilford syndrome was confirmed by analysis of the lamin A gene,
      revealing a heterozygous c.1824C > T (G608G) mutation. CONCLUSION: Hutchinson
      Gilford syndrome is an extremely rare disorder of which the full clinical
      spectrum becomes evident with time. Sclerodermatous changes in the infant can be
      the first manifestation.

PMID- 15726407
TI  - Severe mucitis after sublingual administration of tetrahydrobiopterin in a
      patient with tetrahydrobiopterin-responsive phenylketonuria.

PMID- 15726410
TI  - Surfactant lavage for extracorporeal membrane oxygenation-requiring meconium
      aspiration syndrome--a cheap alternative.

PMID- 15726411
TI  - Familial West syndrome and dystonia caused by an Aristaless related homeobox gene
      mutation.

PMID- 15726412
TI  - Colorectal cancer in two pre-teenage siblings with familial adenomatous
      polyposis.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant disorder that
      characteristically presents with colon cancer in early adult life. We describe a
      Pakistani FAP family in which two sons had an unusually early manifestation of
      colorectal cancer. The index patient presented at 11 years of age with abdominal
      pain, rectal bleeding and iron deficiency anaemia. Colonoscopy showed that the
      colon was carpeted with a myriad of polyps. Oesophago-gastric and duodenal
      endoscopy revealed that polyps had also developed in the duodenum. Multiple
      biopsies indicated neoplastic lesions. The patient underwent a proctocolectomy
      and endoscopic duodenal mucosectomy. The diagnosis of an adenocarcinoma of the
      colon and further adenomatous polyps with low-grade and high-grade dysplasia was
      confirmed by histology. Family screening including a blood test for anaemia and
      bowel examination revealed that his 12-year-old brother was also affected.
      CONCLUSION: Children with familial adenomatous polyposis are at risk for colon
      cancer and emphasise the need for early tumour recognition. Gastrointestinal
      symptoms in children should be thoroughly evaluated and standard screening for
      colonic polyposis should be performed in all individuals with a positive family
      history and/or known mutations in cancer-associated genes, particularly in
      children who are under 10 years of age.

PMID- 15726414
TI  - Homeodomain revisited: a lesson from disease-causing mutations.
AB  - The homeodomain is a highly conserved DNA-binding motif that is found in numerous
      transcription factors throughout a large variety of species from yeast to humans.
      These gene-specific transcription factors play critical roles in development and
      adult homeostasis, and therefore, any germline mutations associated with these
      proteins can lead to a number of congenital abnormalities. Although much has been
      revealed concerning the molecular architecture and the mechanism of homeodomain
      DNA interactions, the study of disease-causing mutations can further provide us
      with instructive information as to the role of particular residues in a conserved
      mode of action. In this paper, I have compiled the homeodomain missense mutations
      found in various human diseases and re-examined the functional role of the
      mutational "hot spot" residues in light of the structures obtained from
      crystallography. These findings should be useful in understanding the essential
      components of the homeodomain and in attempts to design agonist or antagonists to
      modulate their activity and to reverse the effects caused by the mutations.

PMID- 15726413
TI  - Genes and human elite athletic performance.
AB  - Physical fitness is a complex phenotype influenced by a myriad of environmental
      and genetic factors, and variation in human physical performance and athletic
      ability has long been recognised as having a strong heritable component.
      Recently, the development of technology for rapid DNA sequencing and genotyping
      has allowed the identification of some of the individual genetic variations that
      contribute to athletic performance. This review will examine the evidence that
      has accumulated over the last three decades for a strong genetic influence on
      human physical performance, with an emphasis on two sets of physical traits, viz.
      cardiorespiratory and skeletal muscle function, which are particularly important
      for performance in a variety of sports. We will then review recent studies that
      have identified individual genetic variants associated with variation in these
      traits and the polymorphisms that have been directly associated with elite
      athlete status. Finally, we explore the scientific implications of our rapidly
      growing understanding of the genetic basis of variation in performance.

PMID- 15726415
TI  - The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is
      associated with darker skin color in African Americans.
AB  - Skin color, a predictor of social interactions and risk factor for several types
      of cancer, is due to two contrasting forms of melanin, the darker eumelanin and
      lighter phaeomelanin. The lighter pigment phaeomelanin is the product of the
      antagonistic function of the agouti signaling protein (ASIP) on the alpha
      melanocyte stimulating hormone receptor (MC1R). Studies have shown that a single
      nucleotide polymorphism (SNP) in the 3'UTR of the ASIP gene is associated with
      dark hair and eyes; however, little is known about its role in inter-individual
      variation in skin color. Here we examine the relationship between the ASIP
      g.8818A>G SNP and skin color (M index) as assessed by reflectometry in 234
      African Americans. Analyses of variance (ANOVA) were performed to evaluate the
      effects of ASIP genotypes, age, individual ancestry, and sex on skin color
      variation. Significant effects on M index variation were observed for ASIP
      genotypes (F(2,236)=4.37, P=0.01), ancestry (F(1,243)=37.2, P<0.001), and sex
      (F(1,244)=4.08, P=0.05). Subsequent analyses revealed a strong effect on M index
      from ASIP genotypes in African American females (P<0.001). Our study suggests
      that the ASIP G>A polymorphism exhibits a dominant effect leading to lighter skin
      color and that variation in the ASIP gene may have been one of several factors
      contributing to reductions in pigmentation in some populations. Further study is
      needed to reveal how interactions between ASIP and several other genes, such as
      MC1R and P, predict human pigmentation.

PMID- 15726416
TI  - TLR2 Arg677Trp polymorphism in leprosy: revisited.
AB  - We investigated the Toll-like receptor 2 (TLR2) Arg677Trp polymorphism,
      associated with lepromatous leprosy in the Korean population and shown to
      abrogate TLR2-mediated signalling in response to mycobacterial ligands, in 286
      Indian leprosy patients and 183 ethnically matched controls. The case-control
      comparison also involved investigation of possible variation(s) in the promoter
      region of the TLR2 gene. Genotyping results after direct PCR sequencing showed
      that the TLR2 Arg677Trp polymorphism associated with lepromatous leprosy in the
      Korean population is not a true polymorphism of the TLR2 gene and has resulted
      from the variation present in the 93% homologous duplicated region of TLR2 exon 3
      present approximately 23 kb upstream.

PMID- 15726417
TI  - Array CGH detection of a cryptic deletion in a complex chromosome rearrangement.
AB  - Balanced complex chromosome rearrangements (CCR) are extremely rare in humans.
      They are usually ascertained either by abnormal phenotype or reproductive failure
      in carriers. These abnormalities are attributed to disruption of genes at the
      breakpoints, position effect or cryptic imbalances in the genome. However, little
      is known about possible imbalances at the junction points. We report here a
      patient with a CCR involving three chromosomes (2;10;11) and eight breakpoints.
      The patient presented with behavioural problems as the sole phenotypic
      abnormality. The rearrangement, which is apparently balanced in G-banding and
      multicolour FISH, was shown by genomic array analysis to include a deletion of
      0.15-1.5 Mb associated with one of the breakpoints. To explain the formation of
      this rearrangement through the smallest possible number of breakage-and-reunion
      events, one has to assume that the breaks have not occurred simultaneously, but
      in a temporal order within the span of a single cell division. We demonstrate
      that array comparative genomic hybridisation (CGH) is a useful complementary tool
      to cytogenetic analysis for detecting and mapping cryptic imbalances associated
      with chromosome rearrangement.

PMID- 15726418
TI  - BRCA1 variants in a family study of African-American and Latina women.
AB  - We sequenced the entire coding region of BRCA1 to improve our understanding of
      the frequency and nature of BRCA1 variants in African-American and Latina women
      identified from a multiethnic cohort in Los Angeles, California. The study
      included 109 African-American and 140 Latina sibships from families with two or
      more cases of breast or ovarian cancer among first-degree relatives. BRCA1 was
      sequenced in 278 breast or ovarian cancer cases and 229 unaffected sisters. The
      proportion of cases with known disease-causing mutations was low (0.72, 95%
      confidence interval: 0-1.7%). In total, 33 sequence variants were identified,
      including two protein truncation mutations, one deletion, and six silent and 24
      missense variants. Two novel rare variants were identified that appeared to act
      as benign polymorphisms. Four rare variants may be unique to women of African
      descent based on existing literature, and three have been described exclusively
      in Latina women. The frequency of common variants was similar for cases and
      controls, but the frequency of common variants for African-American women
      significantly differed from those previously described for Caucasian women. We
      believe this to be the largest study of high-risk African-American and Latina
      women sequenced for variants in the BRCA1 gene to date.

PMID- 15726419
TI  - A large interstitial deletion encompassing the amelogenin gene on the short arm
      of the Y chromosome.
AB  - Sex tests based on amelogenin are part of various PCR multiplex reaction kits
      widely used for human gender identification and have important applications in
      forensic casework, prenatal diagnosis, DNA databasing and blood sample storage.
      The two most common sex tests based on amelogenin are represented by primer sets
      that delimit a 6-bp deletion on the X chromosome to produce X/Y fragments of
      106/112 or 212/218 bp, respectively. Few cases of AMELY deletion, usually
      considered as polymorphisms, have been reported so far and a detailed
      characterization of the molecular alteration is still lacking. In this study, we
      describe a large interstitial deletion of the Y short arm encompassing the AMELY
      locus in two unrelated individuals. The first case was identified in an
      oligozoospermic, otherwise phenotypically normal, 32-year-old man during the
      screening for Y microdeletions performed on a sample of infertile males. The
      second one was found among amniotic liquid samples tested by quantitative
      fluorescence-polymerase chain reaction and cytogenetic analysis for prenatal
      diagnosis. The extent of the deletion, spanning approximately 2.5 Mb, was better
      characterised by pulsed-field gel electrophoresis, followed by fluorescence in
      situ hybridization and STS marker analysis.

PMID- 15726420
TI  - Storage and secretion of Ag-Aper14, a novel peritrophic matrix protein, and Ag
      Muc1 from the mosquito Anopheles gambiae.
AB  - The gene Ag-Aper14 encodes a novel peritrophic matrix (or peritrophic membrane;
      PM) protein in the mosquito Anopheles gambiae. The Ag-Aper14 protein is merely 89
      amino acids long and has a single putative chitin-binding domain. Prior to blood
      feeding, the Ag-Aper14 protein is stored in secretory vesicles next to the
      epithelial cell lumenal surface. Immunoelectron microscopy has revealed that Ag
      Aper14 co-localizes to the same secretory vesicles as another PM protein, Ag
      Aper1, indicating a common mode of regulated secretion. Conversely, Ag-Muc1, an
      epithelial cell-surface protein, does not co-localize to these secretory vesicles
      and is detected only on the cell surface. After blood feeding, Ag-Aper14 is
      secreted and incorporated into the PM that surrounds the ingested blood.

PMID- 15726421
TI  - Development of A-type allatostatin immunoreactivity in antennal lobe neurons of
      the sphinx moth Manduca sexta.
AB  - The antennal lobe (AL) of the sphinx moth Manduca sexta is a well-established
      model system for studying mechanisms of neuronal development. To understand
      whether neuropeptides are suited to playing a role during AL development, we have
      studied the cellular localization and temporal expression pattern of
      neuropeptides of the A-type allatostatin family. Based on morphology and
      developmental appearance, we distinguished four types of AST-A-immunoreactive
      cell types. The majority of the cells were local interneurons of the AL (type Ia)
      which acquired AST-A immunostaining in a complex pattern consisting of three
      rising (RI-RIII) and two declining phases (DI, DII). Type Ib neurons consisted of
      two local neurons with large cell bodies not appearing before 7/8 days after
      pupal ecdysis (P7/P8). Types II and III neurons accounted for single centrifugal
      neurons, with type II neurons present in the larva and disappearing in the early
      pupa. The type III neuron did not appear before P7/P8. RI and RII coincided with
      the rises of the ecdysteroid hemolymph titer. Artificially shifting the pupal 20
      hydroxyecdysone (20E) peak to an earlier developmental time point resulted in the
      precocious appearance of AST-A immunostaining in types Ia, Ib, and III neurons.
      This result supports the hypothesis that the pupal rise in 20E plays a role in
      AST-A expression during AL development. Because of their early appearance in
      newly forming glomeruli, AST-A-immunoreactive fibers could be involved in
      glomerulus formation. Diffuse AST-A labeling during early AL development is
      discussed as a possible signal providing information for ingrowing olfactory
      receptor neurons.

PMID- 15726423
TI  - Rat enamel contains RP59: a new context for a protein from osteogenic and
      haematopoietic precursor cells.
AB  - We have recently identified a protein, RP59, in bone marrow cells and young
      osteoblasts, in cells involved in bone repair and in young erythroblasts and
      megakaryocytes. Here, we report immunohistochemical data at the light- and
      electron-microscope level indicating that RP59 is also present in newly secreted
      tooth enamel of the rat and in ameloblasts, the formative cells. In enamel
      matrix, RP59 was located proximal to secretory ameloblasts only, i.e. in newly
      secreted material. Distal enamel and enamel in association with maturation stage
      ameloblasts were unlabelled. Secretory ameloblasts contained RP59 in the matrix
      proximal region including Tomes' processes, post-secretory ameloblasts in the
      cell-matrix interface. Western blotting of proteins from tooth germs identified
      RP59 as a band at 90 kD, co-migrating with RP59 from bone marrow and spleen.
      Antisera versus a chemically synthesised RP59 peptide and versus a bacteria
      synthesised protein fragment reacted in the same manner. In situ hybridisation of
      tooth tissue revealed RP59 RNA specifically in ameloblasts. The reverse
      transcription/polymerase chain reaction method identified tooth RNA coding for
      RP59. Sequence analysis indicated that RP59 RNA from tooth and marrow had the
      same sequence. An internal sequence motif was found in rat RP59 resembling a
      signal implicated in secretion of the chicken "engrailed" gene product. The
      findings indicate that RP59 is a genuine product of ameloblasts and that it is
      secreted in the course of enamel formation together with other matrix components.

PMID- 15726422
TI  - Immunocytochemical localization and ontogenic development of alpha-melanocyte
      stimulating hormone (alpha-MSH) in the brain of a pleuronectiform fish, barfin
      flounder.
AB  - Alpha-melanocyte-stimulating hormone (alpha-MSH) is a pituitary hormone derived
      by post-translational processing from proopiomelanocortin and is involved in
      background adaptation in teleost fish. It has also been reported to suppress food
      intake in mammals. Here, we examined the immunocytochemical localization of alpha
      MSH in the brain and pituitary of a pleuronectiform fish, the barfin flounder
      (Verasper moseri), as a first step in unraveling the possible function of alpha
      MSH in the brain. The ontogenic development of the alpha-MSH system was also
      studied. In the pituitary, alpha-MSH-immunoreactive (ir) cells were
      preferentially detected in the pars intermedia. In the brain, alpha-MSH-ir
      neuronal somata were located in the nucleus tuberis lateralis of the basal
      hypothalamus, and alpha-MSH-ir fibers were located mainly in the telencephalon,
      hypothalamus, and midbrain. Alpha-MSH-ir neuronal somata did not project their
      axons to the pituitary. The alpha-MSH-ir neurons differed from those
      immunoreactive to melanin-concentrating hormone. Alpha-MSH cells in the pituitary
      and alpha-MSH-ir neuronal somata in the brain were first detected 1 day and 5
      days after hatching, respectively. The distribution of alpha-MSH-ir cells,
      neuronal somata, and fibers showed a pattern similar to that in adult fish 30
      days after hatching. These results indicate that the functions of alpha-MSH in
      the brain and pituitary are different and that alpha-MSH plays physiological
      roles in the early development of the barfin flounder.

PMID- 15726424
TI  - Bombesin receptor subtype-3 is expressed by the enteric nervous system and by
      interstitial cells of Cajal in the rat gastrointestinal tract.
AB  - Bombesin receptor subtype-3 (BRS-3), a G-protein-coupled orphan receptor, shares
      47% and 55% homology with other known mammalian bombesin receptors. Despite the
      molecular characterization of BRS-3, its function remains unclear as a
      consequence of its low affinity for bombesin and the absence of an identified
      natural ligand. Although the other mammalian bombesin receptors are widely
      distributed in the gut and central nervous system, expression of BRS-3 in the
      gastrointestinal tract has not been previously described. We report the
      expression of BRS-3 mRNA and protein in the tunica muscularis of the rat
      gastrointestinal tract. The mRNA expression pattern was studied by reverse
      transcription followed by quantitative polymerase chain reaction. To identify the
      cellular sites of expression of BRS-3, we performed immunocytochemistry by using
      a N-terminus-specific affinity-purified antiserum. BRS-3 was found to be widely
      expressed in the rat gastrointestinal tract at both the mRNA and protein levels.
      BRS-3-like immunoreactivity (BRS-3-LI) was localized in neurons of the myenteric
      and submucosal ganglia, being primarily concentrated near the neuronal plasma
      membrane, and in fibers distributed in the longitudinal and circular muscle
      layers. In addition, BRS-3-LI was observed in the cell bodies and processes of c
      kit+ interstitial cells of Cajal. These data have functional applications for the
      effects mediated by the activation of BRS-3 on gut motility through distinct
      neuronal and non-neuronal pathways.

PMID- 15726425
TI  - Lack of TrkB and TrkC signaling alters the synaptogenesis and maturation of mossy
      fiber terminals in the hippocampus.
AB  - We have studied the role of endogenous neurotrophins in the formation and
      maturation of intrinsic hippocampal connections in vivo and analyzed the dentate
      granule cell projections in both trkB-/- and trkC-/- mice. Immunohistochemistry
      against calbindin did not show major alterations in the distribution of granule
      cell axons, which were located exclusively in the hilus and the stratum lucidum.
      However, the thickness of the stratum lucidum (mossy fiber termination zone) and
      the density of mossy fiber terminals were reduced in the absence of TrkB
      signaling. Electron-microscopic analyses showed that the fine structure of mossy
      terminals was altered in both trkB-/- and trkC-/- mice. Mutant granule cell
      terminals were smaller than those in wild-type animals and showed a reduction in
      both the number of synaptic contacts and synaptic vesicles. Immunofluorescence
      assays demonstrated that the expression levels of most synaptic-associated
      proteins (v-SNAREs and t-SNAREs) were altered in the mossy fibers of trkB- and
      trkC-deficient mice. Our results therefore reveal that TrkB and TrkC signaling is
      required for the maturation of granule cell axons.

PMID- 15726426
TI  - Phosphorylation of PTEN and Akt in astrocytes of the rat hippocampus following
      transient forebrain ischemia.
AB  - To ascertain whether the PTEN (phosphatase and tensin homolog deleted on
      chromosome 10)/Akt signaling pathway is activated during ischemic brain injury,
      we investigated the expression and phosphorylation of PTEN and Akt by
      immunohistochemistry in the rat hippocampus after transient forebrain ischemia.
      Weak immunoreactivity for PTEN and its phosphorylated form (p-PTEN) was
      constitutively expressed in hippocampal neurons and astrocytes of the control
      rats, but their upregulation was detected mainly in reactive astrocytes in the
      ischemic hippocampus. Increased immunoreactivity for PTEN and p-PTEN occurred
      specifically in astrocytes by day 1 and was sustained for more than 2 weeks. The
      spatiotemporal activation of Akt in the ischemic hippocampus mirrored that of p
      PTEN expression. Post-ischemic activation of Akt, revealed by phosphorylated Akt
      (p-Akt) immunoreactivity, was first detected at day 1 and was maintained for at
      least 2 weeks. Double-labeling experiments revealed that the cells expressing
      PTEN, p-PTEN, or p-Akt were reactive astrocytes expressing glial fibrillary
      acidic protein. These results demonstrate the increased phosphorylation of PTEN
      and Akt in reactive astrocytes of the post-ischemic hippocampus, suggesting that
      the PTEN/Akt pathway is involved in the astroglial reaction in the rat
      hippocampus after transient forebrain ischemia.

PMID- 15726427
TI  - A rare fraction of human hematopoietic stem cells with large telomeres.
AB  - The lack of specific markers for stem cells makes the physical identification of
      this compartment difficult. Hematopoietic stem cells differ in their repopulating
      and self-renewal potential. Our study shows that multiple classes of human
      hematopoietic CD34+ greatly differ in telomere length. Flow-cytometry-based
      fluorescent in situ hybridization and confocal microscopy of CD34+ cells has
      revealed remarkable telomere length heterogeneity, with a hybridization pattern
      consistent with different classes of human hematopoietic progenitor cells. These
      results also point to the existence of a significant clonal heterogeneity among
      primitive hematopoietic cells and provide the first evidence of a rare fraction
      of CD34+ cells with large telomeres in humans.

PMID- 15726429
TI  - Global application of stable hydrogen and oxygen isotopes to wildlife forensics.
AB  - Stable isotopes are being increasingly used in wildlife forensics as means of
      determining the origin and movement of animals. The heavy isotope content of
      precipitated water and snow (deltaD(p), delta(18)O(p)) varies widely and
      systematically across the globe, providing a label that is incorporated through
      diet into animal tissue. As a result, these isotopes are potentially ideal
      tracers of geographic origin. The hydrogen and oxygen isotope tracer method has
      excellent potential where (1) spatial variation of precipitation isotopes exist,
      and (2) strong, mechanistic relationships link precipitation and isotope ratios
      in biological tissue. Here, we present a method for interpolation of
      precipitation isotope values and use it to create global basemaps of growing
      season (GS) and mean annual (MA) deltaD(p) and delta(18)O(p). The use of these
      maps for forensic application is demonstrated using previously published isotope
      data for bird feathers (deltaD(f)) in North America and Europe. The precipitation
      maps show that the greatest potential for applying hydrogen and oxygen isotope
      forensics exists in mid- to high-latitude continental regions, where strong
      spatial isotope gradients exist. We demonstrate that deltaD(f)/deltaD(p)
      relationships have significant predictive power both in North America and Europe,
      and show how zones of confidence for the assignment of origin can be described
      using these predictive relationships. Our analysis focuses on wildlife forensics,
      but the maps and approaches presented here will be equally applicable to criminal
      forensic studies involving biological materials. These maps are available in GIS
      format at http://www.waterisotopes.org.

PMID- 15726428
TI  - Expression of tropism-related genes in regenerating skeletal muscle of rats
      treated with cyclosporin-A.
AB  - This work was undertaken to provide further insights into the expression of
      tropism-related genes in regenerating skeletal muscle of adult rats treated with
      cyclosporin-A (CsA), a calcineurin inhibitor. Rats were treated with CsA for 5
      days and, on the 6th day, were submitted to cryolesion of the soleus muscles. CsA
      treatment continued for 1, 10, and 21 days after cryolesion. Muscles were
      removed, frozen, and stored in liquid nitrogen. Body and muscle weights,
      histological sections stained with toluidine blue, and gene expression of the
      regeneration molecular markers, viz., desmin and neonatal myosin heavy chain,
      were assessed to confirm that cryolesion and CsA treatment were effective during
      the allowed regeneration time. Quantitative reverse transcription/polymerase
      chain reaction demonstrated that myostatin gene expression was not altered by
      either cryolesion or CsA treatment combined with cryolesion. Calpain-3 gene
      expression decreased at 1 day after cryolesion and also following CsA treatment
      combined with cryolesion. However, calpain-3 gene expression was strongly up
      regulated (approximately five-fold) 10 days after cryolesion and returned to
      control levels at day 21. CsA treatment blocked calpain-3 gene expression rise
      induced by 10 days of cryolesion. Atrogin-1 gene expression was decreased at 1
      day after cryolesion and following cryolesion combined with CsA treatment,
      returning to control levels at day 10. These results suggest that (1) calpain-3
      has a differential role in the early and late stages of regeneration in a
      calcineurin-dependent manner, and (2) atrogin-1 is involved in the early stages
      of regeneration independently of calcineurin.

PMID- 15726430
TI  - Sheep grazing and rodent populations: evidence of negative interactions from a
      landscape scale experiment.
AB  - Inter-specific competition, facilitation and predation influence herbivore
      assemblages, but no study has experimentally explored the interactions between
      large ungulates and small rodents. In a fully replicated, landscape scale
      experiment, we manipulated densities of domestic sheep in mountain pastures in
      Norway. We then determined population growth and densities of rodents by live
      trapping in each of the areas with different sheep densities. We found that the
      (summer) population growth rate and autumn density of the field vole (Microtus
      agrestis) was lower at high sheep density. This provides the first experimental
      evidence of negative interactions between an ungulate and small rodent species.
      There was no effect on the bank vole (Clethrionomys glareolus), whose diet
      differs from sheep. Sheep density, therefore, potentially alters the pattern of
      inter-specific population synchrony amongst voles. Our study shows that negative
      interactions between large ungulates and small rodents may be species-specific
      and negative population consequences for the rodent population appear above
      threshold ungulate densities.

PMID- 15726431
TI  - Factors that influence physicians in providing palliative care in rural
      communities in Taiwan.
AB  - GOALS OF WORK: To identify the willingness, influencing factors, and educational
      needs of community physicians in providing palliative care in the rural areas of
      Taiwan. METHODS: A questionnaire was sent to all medical directors of the 140
      government health stations assigned to the rural areas of Taiwan. RESULTS: The
      overall response rate was 62.8% with 85 valid questionnaires retrieved. The
      majority of respondents (84.7%) expressed a willingness to provide palliative
      care if they encountered an advanced cancer patient. However, they would limit
      their services to consultation and referral (93.0% and 87.5%, respectively), and
      were less likely to provide home visits (40.3%) or bereavement support of the
      family (29.2%). With respect to knowledge, the accurate answers to the
      philosophy/principles and clinical practice of palliative care were 93.4% and
      57.3%, respectively. Regarding attitudes, the highest score item in perceiving
      the threat about providing palliative care was "uncomfortable to meet and take
      care of the advanced cancer patient." The highest score item in perceiving
      barriers was "providing palliative care may shorten patient's life, just like
      euthanasia." The results of stepwise logistic regression analysis for the
      willingness to provide home visits showed that only the subjective norms remained
      in the model (OR = 1.87, 95% CI = 1.17-3.01). Educational needs expressed by the
      respondents were ranked as follows: emotional support to, communication skills
      with, and bereavement support for the advanced cancer patients and their
      relatives. CONCLUSIONS: Effective training courses that emphasize the practical
      knowledge of palliative care for community physicians, incorporating palliative
      care into medical education particularly in terms of communication skills and
      ethical roles, and active health policy administration including insurance
      payments, are important for the enhancement of community palliative care in
      Taiwan.

PMID- 15726432
TI  - The Supportive Care Task Force at the University of L'Aquila: 2-years experience.
AB  - The Supportive Care Task Force (SCTF) was established within the Medical Oncology
      Department at the University of L'Aquila in May 2002. The missions of the SCTF
      were to allow systematic evaluation and treatment of symptoms, to warrant
      continuity of care in all phases of disease and to provide medical oncology
      residents with training in the treatment of symptoms. A medical oncologist, two
      senior residents in medical oncology and a registered nurse comprised the SCTF. A
      psychiatrist, two neurologists, a dietician, and two physiotherapists served as
      consultants or on a part-time basis. Four beds in two-bedded rooms inside the
      Medical Oncology Department were reserved to SCTF. A close integration with the
      physicians of the Medical Oncology Department was realised. The only criterion to
      admission was the presence of uncontrolled symptoms. Patients were evaluated and
      monitored with the visual analogue scale for pain and with the Edmonton Symptom
      Assessment Scale (ESAS). The Palliative Prognostic Score (PaP Score) was employed
      to assess the prognosis. Non-clinical needs were evaluated with the Need
      Evaluation Questionnaire (NEQ). Protocols for the treatment of common symptoms
      were available in written form for consultation by physicians, residents and
      nurses. From 1 May 2002 to 31 May 2004, we observed 208 patients: 111 women and
      97 men. The median age was 64.7 (range 28-90) years. Fifty-four patients (25.9%)
      were admitted more than once, for a total of 285 admissions. One hundred ninety
      nine admissions (69.5%) were for supportive care while 86 admissions (30.5%) were
      for supportive care and active treatment. The most frequent symptoms were
      asthenia and anorexia. We registered excellent results regarding the treatment of
      pain, nausea and dyspnea while psychological symptoms, anorexia and asthenia
      proved more difficult to treat. Two hundred twenty patients were discharged: 142
      (49.8%) home; 76 (26.7%) to the Home Care Service and two (0.7%) to others units
      of the hospital. Sixty-five (22.8%) died in our unit.

PMID- 15726433
TI  - Nutrient amounts of ectomycorrhizae analysed by EDX using ESEM and ICP.
AB  - Energy-dispersive X-ray (EDX) analysis coupled with an environmental scanning
      electron microscope (ESEM) was tested as an alternative to the inductively
      coupled argon plasma (ICP) spectrometer method for nutrient analyses of
      ectomycorrhizae. The results of EDX-ESEM and ICP were compared for 12
      ectomycorrhizal morphotypes collected in beech and Scots pine forests in northern
      Brandenburg. The amounts of Al, Ca, Mg and S analysed in the outer hyphal layers
      of the sheath with the EDX-ESEM technique correlated well with the amounts of
      these elements in the whole mycorrhiza as assessed by ICP. For the elements P and
      K, no such correlation existed, indicating an uneven distribution of these
      elements in the ectomycorrhiza. It is concluded that the EDX-ESEM technique could
      be a useful and reliable tool for the analysis of nutrient elements in
      ectomycorrhizae, especially for studies focussing on small-scale soil
      heterogeneity or on infrequent morphotypes.

PMID- 15726434
TI  - Ectomycorrhizas associated with a relict population of Dryas octopetala in the
      Burren, western Ireland II. Composition, structure and temporal variation in the
      ectomycorrhizal community.
AB  - The composition, structure and temporal variation of ectomycorrhizal (EM)
      communities associated with mountain avens (Dryas octopetala) in grass heaths of
      the Burren, western Ireland were assessed by using soil core sampling in two
      permanent plots and 30 other sites (196 cores in total). Of the 34 different EM
      types observed, 11 were common and constituted over 80% of the EM biomass. Four
      EM types, Craterellus lutescens, Tomentella sp., Dryadirhiza fulgens and
      Cenococcum geophilum were the most abundant as measured by EM length and
      frequency of occurrence in cores. The species profile and relative abundances
      were very similar in cores from the permanent plots and different sites in the
      Burren, indicating that they were all representative of the same EM community.
      The below-ground EM community in both plots was compared with production of
      basidiomes, and the latter was found to be an unreliable indicator of EM
      community structure. Temporal variation in the EM community was assessed by
      repeated core sampling of the two permanent plots over a 14-month period (between
      March 1998 and May 1999). No statistically significant shifts in EM abundance
      were found between sampling dates, probably as a consequence of the large
      variation in EM abundance between core samples over the sampling period. No
      significant relationship was found between rainfall, soil moisture or soil
      temperature and fluctuations in EM abundance. Patterns of total EM abundance and
      fluctuations in EM diversity were strongly correlated between the two permanent
      plots over the sampling period. Temporal fluctuations in the dominant EM type,
      Craterellus lutescens, were similar in both plots with respect to mycorrhizal
      length, biomass and relative abundance, and the patterns between both plots were
      positively correlated. EM diversity was negatively correlated with biomass of
      ectomycorrhizas of Craterellus lutescens in both plots, but it was significant
      only in plot 1.

PMID- 15726435
TI  - Ectomycorrhizas associated with a relict population of Dryas octopetala in the
      Burren, western Ireland. I. Distribution of ectomycorrhizas in relation to
      vegetation and soil characteristics.
AB  - The distribution of ectomycorrhizas on Dryas octopetala L in grass heaths of the
      450 km2 karst region known as the Burren in Western Ireland was examined in
      relation to soil factors and vegetation type. Ectomycorrhizas were identified or
      characterised from 56 soil cores from 30 sites, and the occurrence of each
      ectomycorrhizal (EM) type was quantified by estimating the total length of
      mycorrhizal tips of each type. Soil organic matter, total nitrogen, extractable
      phosphorus, pH and depth were the soil factors determined. In total, 24 EM types
      were recorded. The EM community of Dryas roots was significantly more species
      rich in one vegetation type--Hyperico-Dryadetum--than in others (Arctostaphylo
      Dryadetum or Asperulo-Seslerietum). Multiple linear regression analyses indicated
      that soil organic matter and soil depth explained a significant portion of the
      variation in EM abundance, while soil organic matter and extractable phosphorus
      explained a significant portion of the variation in EM diversity. Canonical
      correspondence analysis showed that some individual EM types (e.g. Craterellus
      lutescens, Cenococcum geophilum, Tomentella sp., Boletus sp.) exhibited distinct
      soil preferences, most markedly in relation to soil organic matter, which, in
      this analysis, was the main significant soil variable distinguishing the three
      vegetation types.

PMID- 15726436
TI  - [Oral manifestation of miliary tuberculosis].
AB  - CASE REPORT: We report on the clinical course of a 40-year-old patient with an
      oral manifestation of miliary tuberculosis. In addition to oral mucosa and lung,
      the colon and ileum were also infested. The oral lesions may resemble malignant
      tumors and are difficult to diagnose, especially because tuberculosis has become
      a rare disease in industrialized countries. DISCUSSION: Oral lesions and
      concomitant pulmonary complaints can be a sign for existing tuberculosis.
      Patients with these problems should undergo a chest X-ray and a biopsy from the
      oral mucosa. In addition, tests should be conducted to determine if mycobacteria
      are present in the sputum, gastric fluid, and urine and cultures grown. In cases
      with negative results PCR may detect DNA of Mycobacterium tuberculosis.

PMID- 15726439
TI  - Linac radiosurgery as a tool in neurosurgery.
AB  - Stereotactic radiosurgery is a radiation technique that uses a high radiation
      dose focused on a stereotactic defined intracranial target in single fraction
      with high precision. In the 1980s, linear accelerators were introduced as a tool
      for radiosurgery beneath the already accepted gamma unit. Technique and
      mechanical precision of LINACs have become equal to the gamma unit and LINAC
      radiosurgery became more and more used recently. From January 1996 to August 2003
      we have treated 237 patients with LINAC radiosurgery. A combination of the
      University of Florida system and the X Knife System, developed by Radionics, was
      used in all patients. A number of 110 patients had 161 brain metastases treated,
      whereas the local tumor control rate was 89.4%. The 1-year survival rate was
      54.9% with a median survival of 54 weeks. In 55 patients we have treated 57
      meningiomas, mostly located at the skull base (37 out of 55 patients). Local
      tumor control rate in our patients with skull base meningiomas at 5-year follow
      up was 97.2%. In this time period, we have also treated acoustic schwannoma,
      glioma, pituitary adenoma, arteriovenous malformations and patients with
      trigeminal neuralgia. LINAC radiosurgery has become a daily tool in neurosurgery
      and changed treatment strategies especially in the treatment of brain metastases
      and skull base meningiomas towards a less aggressive and multimodality approach.
      It is not only an alternative to open surgery, but also a very effective adjuvant
      treatment modality in many neuro-oncological patients, which helps us to enhance
      tumor control rate, minimize morbidity and increase postoperative quality of
      life.

PMID- 15726441
TI  - Growth of Bacillus methanolicus in seawater-based media.
AB  - Bacillus methanolicus has been proposed as a biocatalyst for the low cost
      production of commodity chemicals. The organism can use methanol as sole carbon
      and energy source, and it grows aerobically at elevated temperatures. Methanol
      can be made available from off-shore conversion of natural gas to methanol,
      through gas-to-liquid technology. Growth of the organism in seawater-based medium
      would further reduce the costs of chemical production performed near an off-shore
      natural gas source. The growth of strain PB1 (ATCC 51375) in shake flask
      experiments with trypticase soy broth medium showed minimal salt-inhibition at
      the concentration of NaCl in seawater. The ability of B. methanolicus PB1 to grow
      in Pacific Ocean water using methanol as a carbon and energy source was also
      tested. Following a simple adaptation procedure, PB1 was able to grow on methanol
      in semi-defined medium with 100% seawater with good growth yields and similar
      growth rates compared with those achieved on media prepared in deionized water.

PMID- 15726440
TI  - Poly(hydroxyalkanoate) synthase genotype and PHA production of Pseudomonas
      corrugata and P. mediterranea.
AB  - A collection of Pseudomonas corrugata and P. mediterranea strains, two closely
      related species, was evaluated for the presence and variability of pha loci.
      Using PCR methods that specifically amplify segments of medium-chain-length
      poly(hydroxyalkanoate) (mcl-PHA) synthase genes, we demonstrated the presence of
      phaC1 and phaC2 in all P. mediterranea strains tested and in six out of 56
      strains of P. corrugata screened. The remaining 50 strains of P. corrugata
      yielded only the phaC2 subgene fragment on detection by a combined PCR
      restriction endonuclease analysis method or a semi-nested PCR-amplification
      approach. A Southern hybridization study on a representative strain from this
      group, however, indicated the presence of the phaC1 gene. Nucleic acid sequences
      of the subgene phaC fragments of the representative strains from the three groups
      showed an overall similarity ranging from 95% to 100%. The major repeat-unit
      monomers of the mcl-PHAs isolated from these selected strains are beta
      hydroxyoctanoate (33-47 mol%) and beta-hydroxydecanoate (26-36 mol%). These
      results differentiate for the first time the strains of P. corrugata into two pha
      distinguishable groups. This study also documents for the first time the
      production of mcl-PHA in P. mediterranea.

PMID- 15726442
TI  - Production of a novel indole ester from 2-aminobenzoate by Rhodobacter
      sphaeroides OU5.
AB  - Culture supernatants of Rhodobacter sphaeroides OU5 grown in the presence of 2
      aminobenzoate gave an orange-red color-reaction with Salper's reagent, suggesting
      the presence of an indole derivative. This production was light-dependent and
      inducible only with 2-aminobenzoate. Replacement of 2-aminobenzoate with other 2
      substituted benzoates did not result in the formation of indole. Fumarate
      appeared to be the conjugating molecule with 2-aminobenzoate, resulting in the
      formation of an indole derivative. The purified indole derivative was orange
      brown in color, with a yields 0.34 mM from 1 mM 2-aminobenzoate. Infrared
      analysis suggested an indole ester and (1)H NMR analysis indicated an indole
      carboxylate, esterified with a terpenoid alcohol. The indole ester has a mass of
      441 with the molecular formula C(27)H(39)NO(4). The IUPAC name of the compound is
      (3 E,5 E)-14-hydroxy-3,7,11-trimethyl-3,5-tetradecadienyl 2-(hydroxymethyl)-1 H
      indole-3-carboxylate; and the common name given to this compound is sphestrin.

PMID- 15726443
TI  - A cable model for coupled neurons with somatic gap junctions.
AB  - A cable model is presented for a pair of electrotonically coupled neurons to
      investigate the spatial effects of soma-somatic gap junctions. The model extends
      that of Poznanski et al.(1995) in which each neuron is represented by a tapered
      equivalent cable attached to an isopotential soma with the two somas being
      electrically coupled. The model is posed generally, so that both active and
      passive properties can be considered. In the active case a system of nonlinear
      integral equations is derived for the voltage, whilst in the passive case these
      have an exact solution that also holds for inputs modelled as synaptic reversal
      potentials. Analytical and numerical methods are used to examine the sensitivity
      of the soma potentials (in particular) to the coupling resistance.

PMID- 15726444
TI  - Expression of the human FUSED protein in Drosophila.
AB  - The Drosophila segment polarity gene fused, which encodes a serine threonine
      kinase, is required to transmit the Hedgehog (Hh) signal in imaginal discs. To
      explore the functional homology between the human protein FUSED (hFU) and the
      Drosophila protein fused (dFu), we have subjected hFU to a precise and well
      defined Hh signalling assay of Drosophila wing development. In the wildtype, hFU
      affects the expression of Hh target genes leading thus to defects in adult wings.
      In fu mutants, overexpression of hFU cannot rescue the fu phenotype. These
      results suggest that hFU in Drosophila interferes with endogenous Hh signalling
      probably by competing with endogenous dFu when binding its partners but cannot
      perform the normal Fu function.

PMID- 15726445
TI  - Fluoride uptake and resistance to further demineralisation of demineralised
      enamel after application of differently concentrated acidulated sodium fluoride
      gels.
AB  - The objective of this study was to analyse fluoride uptake and microhardness
      alteration of carious-like demineralised enamel after application of differently
      concentrated acidulated sodium fluoride gels and to determine the effect of
      fluoridation on enamel resistance against subsequent demineralisation. Artificial
      caries-like lesions of bovine enamel specimens were treated with sodium fluoride
      gels of different concentration (group A: 1.25%, group B: 0.62%, group C: 0.31%,
      group D: 0.15%; n=20 each group) for 5 min and stored in artificial saliva for 24
      h. This cycle was carried out three times. Subsequently, KOH-soluble and
      structurally bound fluoride (determined at depths of 30, 60, and 90 microm) were
      analysed. In the second part of the study, for each 12 enamel specimens surface
      microhardness was determined before and after demineralisation, after
      fluoridation with the differently concentrated gels A-D, and after a second
      demineralisation. With all groups uptake of KOH-soluble and structurally bound
      fluoride resulted in higher levels than baseline content. Statistical analysis
      revealed significant differences between fluoride uptake among the groups, with
      highest uptake for the 1.25% gel and lowest for the 0.15% gel. Moreover, with all
      gels highest uptake was observed in the outermost enamel layer (P<0.05).
      Microhardness values after second demineralisation increased with increased
      concentration of the applied sodium fluoride gel. Increasing concentration of the
      applied gel implies better protection of the enamel specimens against subsequent
      demineralisation (P<0.05). It is concluded that differently concentrated
      acidulated sodium fluoride gels resulted in concentration-related significant
      uptake of fluoride in carious-like demineralised enamel, leading to a better
      demineralisation protection with increasing fluoride concentration in the gel.

PMID- 15726446
TI  - Panic anxiety, under the weather?
AB  - The relationship between weather conditions and psychiatric disorders has been a
      continuous subject of speculation due to contradictory findings. This study
      attempts to further clarify this relationship by focussing on specific conditions
      such as panic attacks and non-panic anxiety in relation to specific
      meteorological variables. All psychiatric emergencies attended at a general
      hospital in Barcelona (Spain) during 2002 with anxiety as main complaint were
      classified as panic or non-panic anxiety according to strict independent and
      retrospective criteria. Both groups were assessed and compared with
      meteorological data (wind speed and direction, daily rainfall, temperature,
      humidity and solar radiation). Seasons and weekend days were also included as
      independent variables. Non-parametric statistics were used throughout since most
      variables do not follow a normal distribution. Logistic regression models were
      applied to predict days with and without the clinical condition. Episodes of
      panic were three times more common with the poniente wind (hot wind), twice less
      often with rainfall, and one and a half times more common in autumn than in other
      seasons. These three trends (hot wind, rainfall and autumn) were accumulative for
      panic episodes in a logistic regression formula. Significant reduction of
      episodes on weekends was found only for non-panic episodes. Panic attacks, unlike
      other anxiety episodes, in a psychiatric emergency department in Barcelona seem
      to show significant meteorotropism. Assessing specific disorders instead of
      overall emergencies or other variables of a more general quality could shed new
      light on the relationship between weather conditions and behaviour.

PMID- 15726447
TI  - The effect of urban ground cover on microclimate, growth and leaf gas exchange of
      oleander in Phoenix, Arizona.
AB  - We assessed how small patches of contrasting urban ground cover [mesiscape
      (turf), xeriscape (gravel), concrete, and asphalt] altered the microclimate and
      performance of adjacent oleander (Nerium oleander L.) plants in Phoenix, Arizona
      during fall/winter (September-February) and spring/summer (March-September).
      Ground-cover and oleander canopy surface temperatures, canopy air temperatures
      and pot soil temperatures tended to be lowest in the mesiscape and highest in the
      asphalt and concrete. Canopy air vapor pressure deficits were lowest in the
      mesiscape and highest in the asphalt plot. Rates of net photosynthesis of all
      oleander plants were highest in October and May, and declined through mid-summer
      (June-July), when rates tended to be highest in the cooler mesiscape,
      particularly when water was limiting. During fall/winter, oleanders in the
      mesiscape produced 20% less biomass, 13% less leaf area, and had 12% lower
      relative growth rates (R(G)) than those in the other ground covers. Lower
      nighttime temperatures in the mesiscape in December led to oleander frost damage.
      During spring/summer, oleanders in the mesiscape produced 11% more biomass, 16%
      more leaf area, and had 3% higher R(G) than those in the other cover types. The
      effects of urban ground cover on oleander performance were season-specific; while
      oleander growth was greatest in the mesiscape during spring/summer, it was lowest
      during fall/winter and these plants experienced frost damage. Because all
      oleander plants produced >10 times as much biomass during the spring/summer, on
      an annual basis oleanders in the mesiscape produced 5-11% more biomass than
      plants in the warmer ground covers.

PMID- 15726448
TI  - Sudden death in epileptic rats exposed to nocturnal magnetic fields that simulate
      the shape and the intensity of sudden changes in geomagnetic activity: an
      experiment in response to Schnabel, Beblo and May.
AB  - To test the hypothesis that sudden unexplained death (SUD) in some epileptic
      patients is related to geomagnetic activity we exposed rats in which limbic
      epilepsy had been induced to experimentally produced magnetic fields designed to
      simulate sudden storm commencements (SSCs). Prior studies with rats had shown
      that sudden death in groups of rats in which epilepsy had been induced months
      earlier was associated with the occurrence of SSCs and increased geomagnetic
      activity during the previous night. Schnabel et al. [(2000) Neurology 54:903-908]
      found no relationship between SUD in human patients and geomagnetic activity. A
      total of 96 rats were exposed to either 500, 50, 10-40 nT or sham (less than 10
      nT) magnetic fields for 6 min every hour between midnight and 0800 hours (local
      time) for three successive nights. The shape of the complex, amplitude-modulated
      magnetic fields simulated the shape and structure of an average SSC. The rats
      were then seized with lithium and pilocarpine and the mortality was monitored.
      Whereas 10% of the rats that had been exposed to the sham field died within 24 h,
      60% of the rats that had been exposed to the experimental magnetic fields
      simulating natural geomagnetic activity died (P<.001) during this period. These
      results suggest that correlational analyses between SUD in epileptic patients and
      increased geomagnetic activity can be simulated experimentally in epileptic rats
      and that potential mechanisms might be testable directly.

PMID- 15726451
TI  - Effects of morphine and endomorphins on the polysynaptic reflex in the isolated
      rat spinal cord.
AB  - At the spinal level, mu-opioids exert their actions on nociceptive primary
      afferent neurons both pre- and postsynaptically. In the present study, we used an
      in vitro isolated neonatal rat (11-15 days old) spinal cord preparation to
      examine the effects of morphine and the endogenous mu-opioid ligands endomorphin
      1 (EM-1) and endomorphin-2 (EM-2) on the polysynaptic reflex (PSR) of dorsal root
      ventral root (DR-VR) reflex. The actions of mu-opioids on spinal nociception were
      investigated by quantification of the firing frequency and the mean amplitude of
      the PSR evoked by stimuli with 20 x threshold intensity. EM-1 decreased the mean
      amplitude of PSR, whereas EM-2 and morphine decreased the firing frequency. The
      pattern of the effects elicited by morphine was the same as that for EM-2, except
      at high concentration. Naloxonazine, a selective mu(1) opioid receptor
      antagonist, had no significant effect on PSR by itself, but blocked the
      inhibition of PSR firing frequency or amplitude induced by EM-1, -2 and morphine.
      This may suggest that EM-1, EM-2 and morphine modulate spinal nociception
      differently and act mainly at the mu(1)-opioid receptors. Although they all act
      via mu(1)-opioid receptors, their different effects on the PSR may suggest the
      existence of different subtypes of the mu(1)-opioid receptor. The present data is
      also consistent with a further hypothesis, namely, that morphine and EM-2
      activate a subtype of mu(1)-opioid receptor presynaptically, while EM-1 acts
      mainly through another subtype postsynaptically. However, since other reports
      indicate that EM-2, but not EM-1, could stimulate the release of enkephalins or
      dynorphin, presynaptic delta and kappa receptors may be also involved indirectly
      in the different regulation by mu-opioids at the spinal level.

PMID- 15726454
TI  - [Harmonisation of regulatory requirements for clinical trials on medicinal
      products for human use in the Directive 2001/20/EC and complementary guidance.
      Implementation of the 12th Law Amending the German Drug Law].
AB  - Directive 2001/20/EC of the European Parliament and the Council of 4 April 2001
      aims to harmonise national regulations governing clinical trials of medicinal
      products for human use in the European Union. This aim is to be achieved by
      harmonising the legal regulations and administrative provisions in force in the
      Member States, especially with respect to the requirements for starting and
      conducting clinical trials, taking into account international ethical and
      scientific standards (Good Clinical Practice). The goal is to further improve the
      protection of participants in clinical trials and to promote clinical research
      within the European Union. In Germany, the necessary transposition into the
      national Drug Law has taken place in the form of the 12th Law Amending the Drug
      Law of 30 July 2004 as well as complementary implementation provisions. The
      amendments to the German Drug Law affect in particular the official authorisation
      procedure, the involvement of ethics committees as well as the conduct of
      clinical trials on minors. The Directive's requirements have been transposed into
      German law while maintaining the high level of protection for the participants in
      clinical trials which had already existed in German legislation.

PMID- 15726452
TI  - Evidence for 5-HT2B and 5-HT7 receptor-mediated relaxation in pulmonary arteries
      of weaned pigs.
AB  - This study characterizes the relaxant response to 5-hydroxytryptamine (5-HT) in
      prostaglandin F(2alpha) (PGF(2alpha))-precontracted pulmonary arteries of weaned
      pigs. In arterial rings with intact endothelium, the relaxation to 5-HT was
      biphasic. The high affinity component of relaxation to 5-HT (0.1-10 nM) was
      abolished by mechanical removal of the endothelium or after the addition of L: 
      NAME (200 microM), and was inhibited by the 5-HT(2B/2C) receptor antagonist SB
      206553 (1 microM), but not the 5-HT(2C) receptor antagonist SB 242084 (0.1
      microM). Endothelium-intact arteries were also relaxed by the selective 5-HT(2B)
      receptor agonist BW 723C86 (pD(2) 7.7). The relaxant response to BW 723C86 was
      inhibited by 1 microM SB 206553 (pK(B) 6.8). The low affinity component of
      relaxation to 5-HT (>/=30 nM) remained unaffected after mechanical removal of the
      endothelium or the addition of L: -NAME. In endothelium-denuded arterial rings, 5
      HT, 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT), and
      frovatriptan produced monophasic relaxations with pD(2) values of 6.5, 7.5, 5.9,
      and 4.7 respectively. Relaxant responses to the agonists were antagonized by the
      selective 5-HT(7) receptor antagonist SB 269970 (pK(B) 8.2-8.9). The relaxant
      response to the potent 5-HT(7) receptor agonist 5-CT was also antagonized by
      methiothepin (pK(B) 9.6), pimozide (pK(B) 8.2), mesulergine (pK(B) 7.7),
      methysergide (pK(B) 7.4), clozapine (pK(B) 7.6), and spiperone (pK(B) 7.4). The
      estimated pK(B) values argue in favor of an involvement of 5-HT(7) receptors in
      the direct vasorelaxant action of 5-HT in the pulmonary arteries of weaned pigs.
      The relaxant response to 5-CT was associated with an increase in cAMP that was
      surmountably antagonized by SB 269970 (pK(B) 8.6). The present in vitro bioassay
      can be used to characterize new drugs with potential agonist or antagonist
      properties at functional 5-HT(7) receptors.

PMID- 15726455
TI  - [Decree on the implementation of good clinical practice in the conduct of
      clinical trials on medicinal products for human use].
AB  - In Germany, Directive 2001/20/EC is implemented by articles 40 to 42a of the
      Federal Drug Act and by the Decree on Good Clinical Practice. Pivotal provisions
      have been included into the Federal Drug Act, such as those aiming at the
      clinical trial subject's protection and defining responsibilities for the
      evaluation of applications as well as for pharmacovigilance and surveillance. The
      Decree comprises: relevant definitions; requirements for manufacturing,
      importation and labelling of investigational medicinal products; the procedures
      to obtain the ethics committee's opinion and the authorization from the competent
      authority on the trial application and on amendments thereof; documentation and
      information tasks of the investigator, sponsor and competent authority; rules for
      inspection to verify compliance with good clinical and manufacturing practice.
      Finally, the decree lists infringements within the meaning of article 97,
      paragraph 2, no. 31 of the Federal Drug Act, and lays down the necessary
      provisions for a transitional period and the entering into force of the new
      provisions.

PMID- 15726456
TI  - [Reorganization of the procedures and the tasks of the responsible ethics
      committees after the 12th AMG amendment. Concepts of the permanent working group
      of the medical ethics committees in Germany].
AB  - Since 12(th) of August 2004 the EU Directive 2001/20/EG has been implemented into
      the national law. The 12th AMG amendment of 30 July 2004 and the good clinical
      practice decree on the conduct of clinical trials on drugs for human use of 9
      August 2004 have been authorized and must be considered for new clinical trials
      with investigational medical products (drugs). The scope of the changes are to
      increase the quality of clinical trials and to continue the process of
      harmonization within the European Community. Based on the new law the sponsor has
      to apply for approval by the competent authority and for a favourable opinion by
      the responsible ethics committee. Both procedures are independent; a favourable
      opinion of the responsible ethics committee is a necessary condition before
      starting the trial. Thus, the role of the ethics committees has been changed; the
      committees are considered as an institution comparable to an authority to protect
      the rights and safety of human subjects involved in clinical trials. The
      permanent working group of the medical ethics committees in Germany has
      established a procedure to meet these requirements, particularly in the case of
      multicentre clinical trials, where only a single opinion shall be given for each
      member state. This article describes this procedure (application, process of
      ethical consideration among the leading and local ethics committees in
      multicentre trials, responsibilities during the trial).

PMID- 15726457
TI  - [Approval of clinical trials of immunobiological medicinal products at the Paul
      Ehrlich Institute].
AB  - The GCP Directive 2001/20/EG has been implemented in Germany by the 12th Law
      Amending the Drug Law of 6 August 2004, thereby introducing new regulations for
      the performance of clinical trials. The amount of the required documentation has
      increased, but the assessment and the approval of clinical trials as well as
      scientific advice procedures (national or by the EMEA) allow the early discussion
      of many details of the development and the non-clinical and clinical testing of
      the medicinal product with the experts of the Paul Ehrlich Institute (PEI). This
      might shorten the times required for later marketing authorisation procedures. To
      facilitate these new tasks, the PEI has created a new central section "Approval
      of Clinical Trials", which is responsible for the assessment of the clinical
      trial applications and will coordinate the procedures within the institute. The
      main topics of clinical trial applications and the particularities of
      biological/biotechnological medicinal products such as allergens, blood products,
      vaccines, sera/mAb and products for cell and gene therapy as well as the
      differences from chemically defined products are discussed.

PMID- 15726458
TI  - [Recording and reporting adverse reactions in clinical trials. New legal
      provisions according to the 12th Law Amending the German Drug Law (AMG) and the
      Ordinance on GCP (GCP-V)].
AB  - With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV),
      new legal provisions for clinical trials came into force in August 2004. These
      include specific definitions and differentiated reporting obligations affecting
      investigators, sponsors, authorities and ethics committees concerning
      pharmacovigilance in clinical trials. The definitions according to section sign3
      (6-8) GCP-V make clear that these provisions focus on those adverse events and
      adverse drug reactions, which are related to investigational medicinal products.
      In the GCP-V for the first time legally binding provisions for investigators are
      laid down defining obligations to report all serious adverse events to the
      sponsor. The sponsor of clinical trials plays a decisive role concerning the
      evaluation, documentation and reporting to the competent higher authorities,
      ethics committees and investigators involved in the clinical trial. In the GCP-V
      different time limits concerning the reporting for sponsors are laid down. The
      requirements concerning expedited reporting focus on suspected unexpected serious
      adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not
      described in the information on the investigational medicinal product. The time
      limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days,
      while for other SUSARs the time limit is 15 days. Besides the responsibilities on
      expedited reporting the sponsor has to submit a line listing of all serious
      adverse reactions which occurred during the clinical trial and a report on the
      safety of the trial subjects on an annual basis or on request. On the European
      level the harmonisation concerning the provisions on pharmacovigilance in
      clinical trials according to the Directive 2001/20/EC and the Eudravigilance
      database should contribute to reach a faster and more effective exchange of
      safety information related to clinical trials between the different competent
      authorities of the EU member states.

PMID- 15726459
TI  - [GCP inspections of clinical trials].
AB  - The new regulations on clinical trials with medicinal products for human use
      include rules for Good Clinical Practice (GCP) inspections. These rules pertain
      to such inspections as part of the surveillance program of the relevant state
      authorities, in preparation for a decision on the authorization of clinical
      trials by the federal authorities, and pre and post approval GCP-inspections as
      one tool of Good Regulatory Practice (GRP). The overall aim of such inspections
      is to verify compliance with the provisions on GCP and, thus, to ensure the
      protection of trial subjects, the credibility and reliability of clinical trial
      results, and the pro-active protection of patients. Since inspection results have
      to be acknowledged by other member states, there is an increasing importance for
      quality assurance and harmonization of inspection procedures. As in most cases a
      considerable number of sites are involved in the conduct of clinical trials in
      different member states, there is a need for coordination of GCP inspections
      between these states.

PMID- 15726460
TI  - [Quality requirements for investigational medicinal products. The state
      authorities' point of view].
AB  - The relevant authorities must assess the quality of investigational medicinal
      products based mainly on the parameters "safety of the persons subject to a
      clinical study", "adequate reproduction of the drug model defined in the clinical
      trial authorization", and "reliability of documentation". Of these, the safety of
      the people subject to a clinical study is of predominant importance. As a
      consequence, this is the main focus of the authorities. Reliability and integrity
      of the documentation on investigational medicinal products are important for the
      assessment of a manufacturing license application. Therefore, this is also
      subject to the relevant authorities.

PMID- 15726461
TI  - [Quality requirements governing non-commercial clinical trials within the
      framework of clinical drug development in humans in the EU. Challenges,
      opportunities, and questions experienced by treatment centres].
AB  - Therapeutic evidence of a given drug treatment develops via "approval studies"
      and clinical "therapy optimisation studies". Legislation has been faced with the
      challenge of providing common legal guidelines regarding the requirements
      governing such a broad spectrum of studies, and to realize their application.
      Numerous definitions and regulations today provide specifics in a previously
      insufficiently regulated grey area. The European frame-it is hoped-facilitates
      international co-operation. Possibly, clearly phrased legal requirements might
      also improve the co-operation between the pharmaceutical industry and treatment
      centres to work in the interest of patients incapable of giving consent and of
      minors. Requirements regarding the responsibilities of the sponsor, insurance for
      trial subjects, double approval procedures, handling of medicinal products to be
      tested and others are not easily fulfilled under the existing, real-life
      conditions of clinical trials. It is obvious that the cost of clinical trials
      will soar and trial sites and sponsor institutions will have to make investments
      for structural adaptation. In fulfilling those requirements trials might gain in
      procedural quality and probably outcome quality as well. Not every study
      discontinued due to lack in funding will be a true loss. We are, however, faced
      with the real threat of losing established structures of quality control and of
      entering a phase of stagnation in clinical research on rare diseases and "small"
      questions. At present, the challenge lies in co-operating with the authorities to
      explore the scope of those regulations to apply them effectively and in a useful
      manner, so that there will be better quality and increased evidence rather than
      less progress.

PMID- 15726462
TI  - [Risk-benefit evaluation of medicinal products. An element of Health Technology
      Assessment].
AB  - This paper aims to further develop and specify the method and the process of risk
      benefit evaluation for determining the safety of medicinal products in national
      and European pharmaceutical law. The term "safety" (Unbedenklichkeit=the
      relationship between efficacy and harmfulness) is one of the central categories
      of national and European pharmaceutical law. The guaranteeing of the safety of
      pharmaceuticals is not a static but a dynamic and process oriented objective. It
      aims to preserve what has been approved on the one hand, and to increase the
      standard of safety by innovation on the other. A medicinal product is only found
      to be safe if the result of the risk-benefit evaluation is a positive risk
      benefit balance. Safety must be guaranteed permanently through the entire
      lifecycle of the medicinal product. One must differentiate between absolute
      safety, which is related to the individual product, and relative safety, which is
      related to already available medicinal products of the same indication. The
      process of risk-benefit evaluation is determined by the indication of the
      medicinal product. The different types of medicinal products or their different
      mechanisms of action require different risk-benefit evaluations. The established,
      estimated and evaluated benefit has to be compared with the established,
      estimated and evaluated risks of the medicinal product. The comparative risk
      benefit evaluation requires a procedural optimisation of benefits as well as
      minimisation of risks and a reciprocal optimisation of both requirements. If the
      comparison of the benefits and risks of the product results in a negative risk
      benefit balance, the product is rated absolutely unsafe. The product is
      relatively unsafe if its standard of safety is lower than that of already
      available pharmaceuticals of the same indication and the existing safety gap
      (increased benefit or lesser risks) is deemed considerable. Differences in
      benefit and/or differences in risk between the medicinal products compared in the
      risk/benefit evaluation render the assessment more difficult and require
      differentiation. Such differentiation, based on indication, has to be appropriate
      from the doctor's perspective and desirable from the perspective of the patient.
      Both perspectives have to be considered in the risk/benefit evaluation under the
      aspect of risk acceptance ("justifiable").

PMID- 15726463
TI  - [Clinical guidelines. What do doctors and patients get from them].
AB  - Now more than ever physicians need effective management of the constantly
      increasing flood of medical information. The authors discuss possibilities for
      developing clinical guidelines as a core element of this information management
      and the requirements of these possibilities. The development of clinical
      guidelines is a process also suitable for involving patient and consumer
      expertise in health care. Models of involving patients are described and how
      these processes can build an important base for shared decision making of
      physicians and patients.

PMID- 15726464
TI  - World Health Organization, Department of essential drugs and medicines policy.
      WHO Workshop on containment of antimicrobial resistance in Europe, 26-27 February
      2004 in Wernigerode, Germany.

PMID- 15726465
TI  - [15th International AIDS Conference in Bangkok--AIDS in Asia has a thousand
      faces. 1: Access for all? Access to what?].

PMID- 15726470
TI  - Steroids in the Guillain-Barre syndrome: is there a therapeutic window?

PMID- 15726471
TI  - [Conceptual decline in Alzheimer's disease].
AB  - INTRODUCTION: In Alzheimer's disease a gradual and progressive loss of semantic
      information takes place. A question of great importance on both the theoretical
      and practical levels is which concepts are the first to be lost and which are the
      most resistant to deterioration. Some theories maintain that the beginning of the
      disease stimuli belonging to certain conceptual categories are most affected by
      loss. METHOD: A group of twenty-two patients with mild to moderate Alzheimer's
      disease was compared with a group of healthy people of similar age, gender, and
      educational level, in naming pictures of objects from eight semantic categories:
      four in the domain of living things and four in the domain of inanimate objects.
      In each group 16 were women and 6 men. The mean age was 74 in both groups.
      STATISTICAL ANALYSIS: In order to know if differences between Alzheimer patients
      and control subjects are determined by the semantic categories, ANOVAS were
      performed taking the group (patients vs control) and the type of stimulus as
      factors. RESULTS: The scores of the Alzheimer patients are statistically lower
      than those of the control subjects, but differences are determined by the
      features of each stimulus (familiarity, frequency, age of acquisition) more than,
      belonging to a specific category. DISCUSSION: The results indicate that the
      specific characteristics of each stimulus contribute more to concept loss than
      does belonging to a certain category, especially the frequency of use and the age
      of acquisition.

PMID- 15726472
TI  - [Comparison of mixed latency of ulnar and median nerve between wrist and elbow as
      diagnostic test of ulnar neuropathy in elbow].
AB  - INTRODUCTION: Conventional electrodiagnosis of ulnar neuropathy at the elbow is
      based on abnormalities in motor conduction across the elbow. However, sensory
      symptoms are predominant, and an accurate determination of the length of the
      nerve in this segment is difficult to obtain. OBJECTIVE: We present an
      electrodiagnostic technique which helps to avoid these difficulties. MATERIAL AND
      METHODS: We compared the mixed latency of ulnar and median nerve between wrist
      and above the elbow in 172 symptomatic and 407 asymptomatic ulnar nerves.
      RESULTS: We determined that a difference of the mixed latency of ulnar and median
      nerve between wrist and above the elbow equal or higher than 1 ms had a
      sensitivity of 87% to an specificity of 91% for the diagnosis of ulnar neuropathy
      at the elbow. Moreover, a difference between both arms equal to or higher than
      0.3 ms had a sensitivity of 80% and specificity of 91 %. If both conditions are
      present, the test is very specific (98%). CONCLUSIONS: The measurement of the
      difference in mixed latency between ulnar and median nerves from wrist to above
      the elbow is a valuable tool for evaluating patients with suspected ulnar
      neuropathy at the elbow without motor involvement.

PMID- 15726473
TI  - [Classic antiepileptic and new generation antiepileptic drugs: gender differences
      in effectiveness and adverse drug reactions].
AB  - INTRODUCTION: Women are more likely to suffer adverse drug reactions. Moreover
      adverse drug reactions differ depending on gender. The main objective of new
      generation antiepileptic drugs (AED) is to reduce adverse drug reactions while
      maintaining the same effectiveness as the classic ones. OBJECTIVES: a) To
      identify sociodemographic and clinical variables associated with being treated
      with new generation AEDs, and b) to compare effectiveness, averse drug reactions
      and quality of life among patients treated with monotherapy, either with classic
      or with new generation AEDs, examining the potential gender differences. PATIENTS
      AND METHODS: A survey among 990 patients aged 16-64 with epilepsy was carried out
      in 32 Spanish hospitals (response rate: 96 %). For the purposes of this study
      patients treated with monotherapy (n = 496) were selected. The outcome variables
      were: effectiveness in seizure control, adverse drug reactions and three
      dimensions of the SF-36 questionnaire (vitality, mental health and self-perceived
      health status). RESULTS: 21 % of women and 8% of men were treated with new AEDs.
      Women were more likely to be treated with new generation AEDs. Moreover, age of
      epilepsy onset was also positively related to new AEDs and a gradient was found.
      Whereas no differences in effectiveness, adverse drug reactions or quality of
      life were observed among men, among women, those treated with new generation AEDs
      had less adverse drug reactions but, on the other hand, effectiveness for
      controlling seizures was lower. CONCLUSIONS: Women are more likely to be treated
      with new AEDs. Although these new treatments seem to have less adverse drug
      reactions among females, their effectiveness in controlling seizures are lower
      than that of classic AEDs.

PMID- 15726474
TI  - [Importance and factors related to chronic fatigue in multiple sclerosis].
AB  - INTRODUCTION: The importance of fatigue in multiple sclerosis (MS) is determined
      by its high frequency and it is an important cause of disability. OBJECTIVE: To
      determine factors that are related to the presence of chronic fatigue in patients
      with MS. PATIENTS AND METHODS: The series comprises patients with MS,
      consecutively attended in the demyelinizating diseases unit, who met the
      following criteria: clinically definite MS (RR or SP), MS duration of more than
      two years, and no relapses during the previous month. Analyzed variables were as
      follows: chronic fatigue, demographic data, functional systems, EDSS, ISS, ESS,
      disease activity, Hamilton, depression scale GHQ-28, PSQI, and interferon.
      Statistical study: bivariate and multivariate analysis by logistic regression.
      RESULTS: A hundred patients were included, 72 female and 28 male. Mean age was
      39.27 years. Of the 100 patients 88 had RR disease and 12 SP disease. MS mean
      duration was 11.2 years. Mean EDSS 2.54. Chronic fatigue was 53 %. The presence
      of depression increased the probability of chronic fatigue 3.6 fold, and every
      point in PSQI-7 increases it 3.5 fold. CONCLUSION: Depression and the PSQI-7
      subscale (day sleep dysfunction) are the only variables independently related to
      chronic fatigue in patients with MS.

PMID- 15726475
TI  - [Hypoxic-ischemic encephalopathy after ultraviolet radiation session].

PMID- 15726476
TI  - [Bruns' syndrome: description of a case of neurocysticercosis with pathological
      study].
AB  - Bruns' syndrome is characterized by sudden and strong headache, accompanied by
      vomiting, acuphenos and vertigo, triggered by abrupt movement of the head and can
      produce deep coma and death. This can be due to neurocysticercosis by cyst in the
      fourth ventricle, which contains the larval stage of Taenia solium. In the last
      years, new cases of this parasitosis are being seen in Spain because of the
      immigration from endemic areas, but the clinical forms of this infestation are
      not varied. We present a 44 year old man Ecuadorian who has clinical symptoms
      consistent with Bruns' syndrome secondary to cyst in the fourth ventricle that
      progressed badly despite undergoing surgery with ventriculoperitoneal shunt and
      treatment with albendazol. Finally, he was operated with the excision of the
      lesion by means of suboccipital craniectomy. We conclude that this syndrome must
      rule out a cystic or non-cystic, intraventricular lesion and that the appropriate
      manipulation of the cysticerotic ventricular cysts carries a more favourable
      prognosis.

PMID- 15726477
TI  - [L-2 hydroxyglutaric aciduria in a patient with Klinefelter syndrome].
AB  - We present a of 22 years old patient who has a severe cerebellar disease that
      started during the first years of life, borderline mental level, epilepsy and
      Klinefelter syndrome. Brain magnetic resonance (MR) imaging revealed swollen
      white matter with a loss of signal on T1-weighted slices and an increase in
      signal intensity on T2-weighted images in both cerebral hemispheres and in both
      cerebellar dentate nuclei. MRI alterations did not change during the studies
      performed from 4 to 21 years. Blood and urine were analyzed and showed great
      elevation of L-2-hydroxyglutaric acid (L-2-HGA) and more discrete elevation of
      its metabolites and lysine. The parents of the patient are first cousins.

PMID- 15726478
TI  - [Neuropathy of common sciatic nerve secondary to compartment syndrome as a
      complication after bariatric surgery].
AB  - INTRODUCTION: With regards to the use of bariatric surgery on very obese patients
      and prolonged interventions, isolated cases of a compartment syndrome by
      compression and secondary rhabdomyolysis have been described. We describe a case
      which presented with a compartment syndrome, rhabdomyolysis and neuropathy of the
      common sciatic nerve. CLINICAL CASE: A 39 year old male with morbid obesity and
      high blood pressure, who after being subjected to 5 hours long bariatric surgical
      intervention, presented with intense pain, muscle binding and paresis in the
      musculature dependent on left common sciatic nerve. A creatinkinase (CK) level of
      78,000 IU and volume increase of the left gluteal compartment were noted. On
      serial computarized tomography scans this increased leading to gluteal atrophy
      and ischiotibials. Evolution was negative without functional recovery and poor
      pain control. The patient presented with a compartment syndrome and secondary
      rhabdomyolysis triggered by the pressure on the gluteal zone on the operating
      table. The prolonged duration of the surgery, obesity and microvascular
      affectation due to hypertension, could be factors implicated in the development
      of the syndrome. The affectation of the sciatic nerve, not described as a
      complication of this type of surgery, is explained by pressure exercised on the
      compartment block on the sciatic nerve, with secondary ischaemia. CONCLUSIONS:
      Early determination of CK, carrying out postural changes during surgery and early
      post-operative neuromuscular examination, looking for signs of compartment
      syndrome, should be systematically carried out after bariatric surgery. The early
      carrying out of a decompressive fasciotomy considering a compartment syndrome
      could reduce or avoid the neurological complications.

PMID- 15726479
TI  - [Pilot study of the neuropsychological test: render therefore unto Caesar the
      things which are Caesar's].

PMID- 15726480
TI  - [Psychogenic disorders].

PMID- 15726481
TI  - [Saint Orosia's convulsionaries].
AB  - Annual outbreaks of mass motor hysteria have been observed in the past during
      some religious celebrations. In Jaca, a Northern Spanish town close to the
      Pyrenees, the convulsionaries have been well known since the eleventh century,
      though little attention has been paid to this phenomenon in the medical
      literature. Pilgrims from remote parts of the valleys gathered in procession on
      June 25th in front of Saint Orosia sarcophagus. Epileptics, psychotics, the
      paralyzed and hysterics joined the procession looking for healing together with
      in exorcist rituals. Reig and Gasco, a military physician, described in 1881 the
      atmosphere of fervour, ignorance and vestigial paganism accompanying these
      unusual behaviours. Saint Orosia's convulsionaries ended in 1947 following
      prohibition by local Catholic Authorities, probably the recurrent outbreak of
      mass motor hysteria lasting to most recent years in Europe.

PMID- 15726482
TI  - The sweating response of elite professional soccer players to training in the
      heat.
AB  - Sweat rate and sweat composition vary extensively between individuals, and
      quantification of these losses has a role to play in the individualisation of a
      hydration strategy to optimise training and competitive performance. Data were
      collected from 26 male professional football (soccer) players during one 90 min
      pre-season training session. This was the 2nd training session of the day,
      carried out between 19.30 and 21.00 h when the mean +/- SD environment was 32 +/-
      3 degrees C, 20 +/- 5 %rh and WBGT 22 +/- 2 degrees C. Training consisted of
      interval running and 6-a-side games during which the average heart rate was 136
      +/- 7 bpm with a maximum rate of 178 +/- 7 bpm (n = 19). Before and after
      training all players were weighed nude. During training all players had free
      access to sports drinks (Gatorade) and mineral water (Solan de Cabras). All drink
      bottles were weighed before and after training. Players were instructed to drink
      only from their own bottles and not to spit out any drink. No player urinated
      during the training session. Sweat was collected by patches from the chest, arm,
      back, and thigh of a subgroup of 7 players. These remained in place for the first
      15 - 30 min of the training session, and sweat was analysed for sodium (Na (+))
      and potassium (K (+)) concentration. Body mass loss was 1.23 +/- 0.50 kg (ranging
      from 0.50 to 2.55 kg), equivalent to dehydration of 1.59 +/- 0.61 % of pre
      training body mass. The sweat volume lost was 2193 +/- 365 ml (1672 to 3138 ml),
      but only 972 +/- 335 ml (239 to 1724 ml) of fluid was consumed. 45 +/- 16 % of
      the sweat volume loss was replaced, but this ranged from 9 % to 73 %. The Na (+)
      concentration of the subgroup's sweat was 30.2 +/- 18.8 mmol/l (15.5 to 66.3
      mmol/l) and Na (+) losses averaged 67 +/- 37 mmol (26 to 129 mmol). The K (+)
      concentration of the sweat was 3.58 +/- 0.56 mmol/l (2.96 to 4.50 mmol/l) and K
      (+) losses averaged 8 +/- 2 mmol (5 to 12 mmol). The drinking employed by these
      players meant that only 23 +/- 21 % of the sweat Na (+) losses were replaced:
      This ranged from replacing virtually none (when water was the only drink) to
      replacing 62 % when the sports drink was consumed. These elite soccer players did
      not drink sufficient volume to replace their sweat loss. This, however, is in
      accord with data in the literature from other levels of soccer players and
      athletes in other events. These measurements allow for an individualisation of
      the club's hydration strategy.

PMID- 15726483
TI  - The chemoreflex in young boys and girls.
AB  - In order to determine the influence of the chemoreflex on the cardiovascular
      system of young children, 35 boys and 35 girls (all 7 - 9 years old) performed
      three minutes of 30 % maximal voluntary contraction (MVC) static handgrip (SHG)
      exercise followed by four minutes of blood flow occlusion in the previously
      exercised arm, and then six minutes of passive recovery. Heart rate (HR) and
      blood pressure (BP) were measured each minute. Twenty girls performed a second
      occlusion trial to determine reliability. Reliability coefficients for HR (R =
      0.51 - 0.78), diastolic (R = 0.46 - 0.81) and systolic (R = 0.57 - 0.78) BP
      throughout the occlusion trial were moderately high. There was a similar increase
      in HR (19 +/- 8 vs. 16 +/- 10 %), diastolic (34 +/- 12 vs. 34 +/- 16 %) and
      systolic (18 +/- 9 vs. 15 +/- 7 %) BP in boys and girls, respectively, during
      three minutes 30 % MVC exercise. During the occlusion period, diastolic (43 +/-
      31 vs. 47 +/- 26 %) and systolic (51 +/- 25 vs. 54 +/- 32 %) BP dropped similarly
      during minute one but remained elevated significantly above baseline in both boys
      and girls the entire four-minute period. During the recovery period, minute one
      SBP and DBP dropped similarly in boys (23 +/- 37, 20 +/- 37 %) and girls (20 +/-
      38, 12 +/- 38 %), respectively. In boys and girls DBP remained significantly
      above baseline the entire recovery period. HR in boys and girls returned to
      baseline immediately following SHG exercise and remained there through recovery.
      In conclusion, as reported in adults, the drop in HR to baseline during post
      exercise ischemia with a concomitant maintenance of BP significantly above
      baseline indicates that at least two separate mechanisms, with varying influence,
      are responsible for HR and BP control in young children. Further, the chemoreflex
      operates similarly in young boys and girls.

PMID- 15726484
TI  - Acute and chronic exposition of mice to severe hypoxia: the role of
      acclimatization against skeletal muscle oxidative stress.
AB  - The role of acclimatization and the effect of persistent severe hypoxia (7000 m)
      were analyzed in mice soleus muscle with respect to oxidative stress (glutathione
      redox status) and damage markers (TBARS and SH protein groups), NAG and SOD
      activities and HSP70 expression. Forty mice were divided into one normobaric
      normoxic control group and four hypobaric-hypoxic experimental groups (n = 8).
      One experimental group (1 D) was acutely exposed to a simulated altitude of 7000
      m in a hypobaric chamber for 1 day. Another experimental group (ACCL + 1 D) was
      exposed to a 3 days acclimatization period plus 1 day of hypoxia exposure at 7000
      m. The third experimental group (ACCL + 8 D) was exposed to the same
      acclimatization protocol, remaining 8 subsequent days at 7000 m. The fourth
      experimental group (8 D) was chronically exposed without acclimatization. ACCL +
      1 D showed a significant decrease (p < 0.05) in oxidative stress and damage
      compared to the 1 D group. Concerning chronic severe hypoxia, acclimatization was
      truly vital, since 8 D animals died after 5 days of exposure. Oxidative stress
      and damage markers in ACCL + 8 D tended to gradually increase throughout the 8
      days of the hypoxic period. Total SOD activity did not change in 1 D compared to
      control; however, it increased significantly (p < 0.05) in ACCL + 1 D and ACCL +
      8 D. HSP70 expression followed the observed oxidative stress and damage pattern,
      suggesting a protective role against hypoxia-induced oxidative stress. The
      present study supports the hypothesis that acclimatization attenuates oxidative
      stress and damage induced by acute hypoxia, although a trend to a gradually
      increased oxidative deleterious effect in skeletal muscle seems to occur during
      persistent severe hypoxia even after a previous acclimatization period.

PMID- 15726485
TI  - Thicker radial cortex in physically active prepubertal girls compared to
      controls.
AB  - This study was carried out to investigate the effects of physical activity on
      cortical bone of the radius in a population of prepubertal girls. Forty-nine
      healthy girls, 17 actives (10.62 +/- 1.56 years) and 32 controls (9.84 +/- 1.23
      years) participated in this study. The active group was involved in gymnastics,
      judo, and dance on average 7.76 +/- 3.94 h/week. Bone mineral content (BMC) and
      density (BMD) were performed at the distal third of the non-dominant radius using
      DXA. The lean mass of the non-dominant forearm was derived from the total body
      analysis performed with DXA. In order to obtain bone cortical thickness, standard
      radiographs of the non-dominant radius were scanned and computed using a software
      program based on radiogrammetry. BMD and BMC values were higher in actives than
      in controls. Cortical thickness at the ulnar side correlated significantly with
      all the anthropometric and densitometric values as well as the duration of
      training. In addition, cortical thickness at the ulnar side was significantly
      higher in the actives compared to the controls. After adjustment for the duration
      of training per week, cortical thickness of the ulnar side did not differ any
      more between actives and controls. The same observation was obtained after
      adjustment for the forearm lean mass. In our active population, physical practice
      seemed to have induced greater BMC and higher cortical thickness than those
      observed in the sedentary.

PMID- 15726486
TI  - Avulsion fracture of inferior pole of patella and tibial spine--a case report of
      rare combination of knee injury.
AB  - A rare sport injury having patellar fracture and anterior cruciate ligament
      avulsion fracture is being reported. This case was noteworthy as it involved rare
      combination of two separate injuries often seen in sportsmen. Our experience with
      operative intervention and postoperative rehabilitation with a supervised
      physiotherapy regimen has yielded good results.

PMID- 15726487
TI  - Relationships between left ventricular morphology, diastolic function and oxygen
      carrying capacity and maximal oxygen uptake in children.
AB  - Little attention has been paid to children with respect to factors controlling
      maximal oxygen uptake (V.O (2max)). This study was therefore specifically
      designed to examine the potential relationships between cardiac size, diastolic
      function and O (2) carrying capacity with maximal aerobic capacity. Specifically,
      body size indices (body surface area, lean body mass), resting left ventricular
      dimensions and filling characteristics, blood haemoglobin concentration as well
      as V.O (2max) established during a maximal cycle exercise test were assessed in a
      large cohort (n = 142) of healthy 10 - 11 year old boys and girls. Results were
      compared between groups of low (< 50, L), moderate (50 - 60, M) and high (> 60,
      H) V.O (2max) (ml . min (-1) . kg (-1) of lean body mass). Moreover, potential
      contributors to V.O (2max) variance were investigated using univariate and
      multivariate regression analyses over the overall population. The major results
      show no differences between the 3 groups for all diastolic and systolic function
      indices as well as blood haemoglobin and systemic vascular resistances (used as
      an index of afterload). None of these variables emerged from regression analyses
      as potential predictors of V.O (2max.) After accounting for body size variation,
      heart dimensions, and especially left ventricular internal dimensions, differed
      between H and M and L and were associated with higher cardiac filling and
      subsequently stroke volume. Strong relationships between V.O (2max) and heart
      dimensions were noticed, due primarily but not exclusively to the influence of
      body size. After adjusting for lean body mass, end-diastolic diameter contributed
      modestly (8 %) but significantly to V.O (2max) variance, which is biologically
      meaningful.

PMID- 15726488
TI  - Aerobic and functional capacities in a selected active population of European
      octogenarians.
AB  - Master athletes are often considered to represent the ideal rate of decline of
      aerobic function; however, most of the studies interested in active elderly
      people are often limited to people younger than 75. We aimed to determine the
      physiological adaptations and aerobic fitness in a selected European population
      of active octogenarians during maximal and submaximal exercise tests. Aerobic
      capacity was measured during maximal incremental tests on treadmill (TR) and
      cycle-ergometer (CE) and functional capacity during a 6-minute walk test (6-MWT)
      in 17 subjects aged 81.2 +/- 0.8 years. Pulmonary gas exchange and heart rate
      (HR) were continuously measured during the different exercise tests. Maximal
      oxygen consumption (V.O (2max)) on TR and CE was significantly higher than
      predicted values (TR: 28.7 +/- 1.2 vs. 17 +/- 0.5 ml . kg (-1) . min (-1); CE: 23
      +/- 1.2 vs. 16 +/- 0.6 ml . kg (-1) . min (-1) for measured and predicted values
      respectively). V.O (2max) and HR (max), as well as V.O (2) and HR at the
      ventilatory threshold (V.O (2)T (V.E) and HR T (V.E)) were significantly higher
      on TR than on CE (HR (max): 144 +/- 4 vs. 138 +/- 4 bpm; V.O (2)T (V.E): 22.5 +/-
      0.8 vs. 17.7 +/- 0.9 ml . kg (-1) . min (-1) for TR and CE respectively). V.O
      (2)T (V.E) and HR T (V.E) on TR were equivalent to V.O (2) and HR measured during
      the 6-MWT. HR T (V.E) on TR and mean HR during the 6-MWT were strongly correlated
      (R = 0.82, p < 0.01). Maintenance of regular physical activity provides high
      aerobic fitness, in octogenarians, as was shown by the higher values of our
      subjects in comparison to predicted values. Moreover, the close relation between
      the intensity developed at T (V.E) on TR and 6-MWT could support the idea that a
      walk test is a submaximal test performed at high intensity that could provide a
      basis for exercise prescription in an individualized manner in active elderly
      people.

PMID- 15726489
TI  - Spatiotemporal consistency of trajectories in gymnastics: a three-dimensional
      analysis of flic-flac.
AB  - Sport performance during the execution of closed skills combines specific body
      and limb movements into codified patterns where stability and consistency may be
      more important than variability. Repeated sport movements can be investigated to
      assess the consistency of body trajectories. More consistent trajectories will
      result in more repeatable movements. The present study quantified the short-term
      consistency of body trajectories during the performance of the backward flic
      flac, a technique of floor gymnastics. Nine experienced gymnasts (six men, three
      women), all of national level, performed 10 repetitions of backward flic-flac. An
      optoelectronic instrument was used for the detection of the three-dimensional
      movement of 13 body landmarks. The spatiotemporal consistency of repeated
      landmark trajectories was measured by the standard deviation between standardized
      trajectories. The results showed smaller standard deviation (larger consistency
      between landmark trajectories) in female than in male gymnasts. The analysis of
      the consistency of landmark trajectories could help gymnasts indicating which
      parts of the body do not repeat a selected movement with sufficient accuracy.

PMID- 15726490
TI  - Somatic and physical traits affecting sprint swimming performance in young
      swimmers.
AB  - The aim of this study was to examine the relationship between anthropometry,
      physical capacity, and sprint swimming performance in swimmers of both genders
      aged 12 - 14 years old. Anthropometric characteristics (body height and mass,
      total upper extremity, hand and foot lengths, chest circumference, certain body
      breadths, and skinfolds), as well as leg explosiveness (horizontal jump) and arm
      strength (handgrip strength test) were evaluated in 263 competitive swimmers (178
      boys and 85 girls) aged 12 - 14 years. Skeletal age was assessed with the Tanner
      Whitehouse method. All variables, except for the ankle and shoulder flexibility
      as well as the skeletal age, correlated with 100 m freestyle performance in boys
      (r = - 0.46 to - 0.73, p < 0.01). Using a split-sample approach, upper extremity
      length, horizontal jump, and grip strength were detected as significant
      predictors of 100 m freestyle performance in boys (R (2) = 0.59, p < 0.01). In
      girls, body height, upper extremity and hand length, shoulder flexibility, and
      horizontal jump were all significantly related to 100 m freestyle time (r = -
      0.22 to - 0.31, p < 0.05) but the degree of association was markedly lower than
      in boys. In addition, only 17 % of the variance in performance was explained by a
      combination of body height, hand length, and horizontal jump in girls. These
      results suggest that 100 m freestyle performance can be partially explained by
      anthropometry and physical capacity tests in young swimmers. The contribution of
      these factors to sprint swimming performance is different in boys and girls and
      this requires further research. These findings could be used for male young
      swimmers' selection.

PMID- 15726491
TI  - EMG activity does not change during a time trial in competitive cyclists.
AB  - The purpose of the present study was to measure the electromyographic (EMG)
      activity of four lower limb muscles and the propulsive torque during a cycling
      time-trial (TT). Nine competitive cyclists (V.O (2max): 73.8 +/- 5.3 ml . min (
      1) . kg (-1)) performed two tests separated over a one-week period on a friction
      load cycle ergometer equipped with a SRM crankset scientific system: 1) a
      continuous incremental test for the determination of the peak power output (PPO);
      and 2) a 30-min TT test at a self-selected work intensity. The EMG activity of
      the vastus medialis (VM), the rectus femoris (RF), the biceps femoris (BF), and
      the gastrocnemius medialis (GAS), and the propulsive torque were recorded every 5
      min for 10 s. There was no time effect on the power output, the pedalling
      cadence, and the mean propulsive torque. The EMG activity of the VM and the RF
      muscles was unchanged during the TT (p > 0.05). The EMG activity of the two knee
      flexor muscles (BF and GAS) tended to increase with time but it was not
      significant (p > 0.05). The EMG/torque of the VM and the RF muscles tended to
      decrease with time but it was not significant (p > 0.05). The lack of increase in
      the EMG activity of the four investigated muscles seems to indicate that the
      subjects performed the TT test at a muscular work steady-state.

PMID- 15726492
TI  - Boxing and "commotio cordis": ECG and humoral study.
AB  - The objective of the study was to analyze the presence of myocardial damage in
      relation to official boxing matches. Low-energy chest wall impact could be
      responsible for sudden cardiac death, i.e. commotio cordis. As boxing is a
      traumatic sport in which thoracic hits usually occur, it seems interesting to
      know if there are any significant cardiac changes during official bouts. Fifteen
      amateur boxers, participating in the semifinals of the Italian Championship were
      investigated. A standard ECG before, immediately after, 1 hour and 12 hours after
      the match were obtained from each athlete to analyze atrio-ventricular
      conduction, QRS axis and duration, and ventricular repolarization. A blood sample
      was also obtained before and 12 hours after the match for analysis of total
      creatin-phosphokinase, myoglobin, and T-troponin. After the fight, the following
      significant changes were encountered: higher QRS voltages, lowering of J-point
      and ST segment in lateral leads, higher ST-slope, lower T-wave amplitude, shorter
      T-wave peak time, and shorter QT interval. When the last 2 parameters were
      corrected for heart rate, no differences were observed for QTc, while T-wave peak
      time significantly increased. All these changes persisted until one hour after
      the match. Moreover, 3/15 boxers (20 %) showed marked ventricular repolarization
      anomalies in lateral leads after the contest, persisting for 12 hours in one
      case. However, no athlete had clinical and humoral signs of myocardial damage
      following the match. It was concluded that no clinical and humoral signs of
      myocardial damage were found after amateur boxing matches, although ventricular
      repolarization abnormalities can be found on ECG in 20 % of boxers, probably due
      to sympathetic hyper-activity related to the agonistic event.

PMID- 15726493
TI  - Social cognitive theory variables associated with physical activity among high
      school students.
AB  - The purpose of this study was to describe the relationships between Social
      Cognitive Theory (SCT) variables and frequency of moderate-vigorous physical
      activity in a sample of high school students. Days of moderate and vigorous
      physical activity were assessed using a previously validated one-day recall
      instrument administered on seven consecutive days. The SCT variables tested were:
      self-regulation, social situation, social outcome expectations, physical
      appearance outcome expectations, general health outcome expectations, negative
      outcome expectations, self-efficacy for ability, and self-efficacy for barriers.
      The SCT variables studied are potentially modifiable via educational
      interventions. Results revealed that 15 % of the subjects reported 3 or more days
      of physical activity. Four of the SCT were retained in the regression model
      accounting for 31 % of the variance in days or moderate-vigorous physical
      activity. SCT is useful for understanding frequency of moderate-vigorous physical
      activity among adolescents.

PMID- 15726494
TI  - The growth factor myostatin, a key regulator in skeletal muscle growth and
      homeostasis.
AB  - Skeletal muscle possesses the ability to both respond and adapt to changing
      environmental stimuli, leading to a set of metabolic and morphological
      adaptations, which allow it to better meet the energy demands of sustained
      physical activity. Great progress has been achieved over the past years by means
      of innovative molecular techniques, which has led to the discovery of new growth
      factors and the identification of molecular mechanisms involved in the regulation
      of muscle development. These findings provide new starting points to understand
      the molecular mechanisms involved in the adaptation of skeletal muscle to
      exercise training. One of these new identified growth factors is myostatin, a
      member of the transforming growth factor-beta family of proteins that has been
      demonstrated to play a fundamental role in the regulation of skeletal muscle
      growth during embryogenesis. Blocking of the myostatin signalling transduction
      pathway by specific inhibitors and genetic manipulations has been shown to result
      in a dramatic increase of skeletal muscle mass. This review focuses on the
      importance of myostatin in mediating skeletal muscle homeostasis in response to
      training as well as during the progress of myogenic disease, like atrophy or
      dystrophy. Manipulations of myostatin signalling may be useful for agriculture
      applications, treatment of muscle diseases, inhibition of muscle atrophy and last
      but not least as life style drugs in antiaging therapies or manipulations of the
      muscle to fat ratio. Drugs with the ability to modulate myostatin signalling may
      have the potential to enhance physical performance in athletes and therefore they
      probably represent a new class of doping substances.

PMID- 15726495
TI  - Effects of the removal of vision on body sway during different postures in elite
      gymnasts.
AB  - The aim of this study was to analyse the effects of the removal of vision on
      postural performance and postural control in function of the difficulty and
      specificity of the posture. Twelve elite gymnasts were instructed to be as stable
      as possible with eyes open and eyes closed in three postures: bipedal, unipedal,
      and handstand ranked from the less difficult and less specific to the more
      difficult and more specific. The ratios eyes closed on eyes open, computed on CP
      surface and CP mean velocity, which respectively represents postural performance
      and postural control, were similar in the bipedal and handstand postures. They
      were highly increased in the unipedal one. The effect of the removal of vision
      and so the role of vision on body sway was not directly linked to the difficulty
      or specificity of the posture; other tasks' characteristics like the segments
      configuration also played a role.

PMID- 15726496
TI  - Identification of a novel LRRK2 mutation linked to autosomal dominant
      parkinsonism: evidence of a common founder across European populations.
AB  - Autosomal dominant parkinsonism has been attributed to pathogenic amino acid
      substitutions in leucine-rich repeat kinase 2 (LRRK2). By sequencing multiplex
      families consistent with a PARK8 assignment, we identified a novel heterozygous
      LRRK2 mutation. A referral sample of 248 affected probands from families with
      autosomal dominant parkinsonism was subsequently assessed; 7 (2.8%) were found to
      carry a heterozygous LRRK2 6055G-->A transition (G2019S). These seven patients
      originate from the United States, Norway, Ireland, and Poland. In samples of
      patients with idiopathic Parkinson disease (PD) from the same populations,
      further screening identified six more patients with LRRK2 G2019S; no mutations
      were found in matched control individuals. Subsequently, 42 family members of the
      13 probands were examined; 22 have an LRRK2 G2019S substitution, 7 with a
      diagnosis of PD. Of note, all patients share an ancestral haplotype indicative of
      a common founder, and, within families, LRRK2 G2019S segregates with disease
      (multipoint LOD score 2.41). Penetrance is age dependent, increasing from 17% at
      age 50 years to 85% at age 70 years. In summary, our study demonstrates that
      LRRK2 G2019S accounts for parkinsonism in several families within Europe and
      North America. Our work highlights the fact that a proportion of clinically
      typical, late-onset PD cases have a genetic basis.

PMID- 15726497
TI  - Gene-environment interaction effects on the development of immune responses in
      the 1st year of life.
AB  - Asthma is a common disease that results from both genetic and environmental risk
      factors. Children attending day care in the 1st year of life have lower risks for
      developing asthma, although the mechanism for this "day care" effect is largely
      unknown. We investigated the interactions between day care exposure in the 1st 6
      mo of life and genotypes for 72 polymorphisms at 45 candidate loci and their
      effects on cytokine response profiles and on the development of atopic phenotypes
      in the 1st year of life in the Childhood Onset of Asthma (COAST) cohort of
      children. Six interactions (at four polymorphisms in three loci) with "day care"
      that had an effect on early-life immune phenotypes were significant at P<.001.
      The estimated false-discovery rate was 33%, indicating that an estimated four P
      values correspond to true associations. Moreover, the "day care" effect at some
      loci was accounted for by the increased number of viral infections among COAST
      children attending day care, whereas interactions at other loci were independent
      of the number of viral infections, indicating the presence of additional risk
      factors associated with day care environment. This study identified significant
      gene-environment interactions influencing the early patterning of the immune
      system and the subsequent development of asthma and highlights the importance of
      considering environmental risk factors in genetic analyses.

PMID- 15726499
TI  - Use of non-degenerate human osteochondral tissue and confocal laser scanning
      microscopy for the study of chondrocyte death at cartilage surgery.
AB  - Although autologous osteochondral grafting has been widely applied in humans,
      most in vitro work has been on animal models. The aims of this study were to: (i)
      elaborate a full thickness human femoral condylar model using discard material
      from knee arthroplasty resections, and (ii) use this model to assess chondrocyte
      viability in response to surgical trauma. Homogeneous regions of human lateral
      femoral condyle bone-cartilage were procured from knee arthroplasty resections.
      These were graded prospectively, firstly by visual inspection, and then by
      confocal laser scanning microscopy (CLSM). Samples were subjected to tests of
      tissue hydration, including analysis of water content and swelling after excision
      from underlying bone. Surgical cuts were made in explants that were
      macroscopically and microscopically normal (i.e. Grade 0). Associated margins of
      death were assessed from both transverse and surface perspectives. Thirty-nine
      samples were obtained from anterior and distal femoral cuts (16 knees from 13
      patients) for (1) macroscopic grading, (2) microscopic analysis, (3) analyses of
      water content as cut and on re-equilibration after excision from bone. Thirteen
      were Grade 0 on macroscopic viewing--however one showed fibrillation on
      microscopy and was therefore reassigned Grade 1. Grade 0 tissue had a water
      content of 73.8+/-0.38%, in agreement with control values from the literature.
      Tissues of Grades 2 and 3 were significantly (P=0.03, and P=0.004) more hydrated
      (76.0+/-0.59%, 76.7+/-0.99%) than Grade 0 tissue. Grade 0 tissue from the
      anterior cut did not swell significantly following excision from subchondral
      bone. However Grade 0 tissue from the distal cut showed a small but statistically
      significant (P=0.019) increase in water content (1.68+/-0.39%) following
      excision. With increasing grade there was increased tendency to swell off the
      bone (P<0.0001). Transverse imaging showed that the Acufex MP surgical harvester
      caused a greater margin of cell death (211+/-18.3 microm) in the superficial zone
      (SZ) than the mid-zone (50.5+/-13.6 microm; P=0.022), or SZ death from a scalpel
      cut (33.0+/-8.5 microm; P=0.0009). Similarly, in unfixed samples viewed from the
      surface perspective, the margin of death for the surgical harvester (277+/-7.2
      microm) was significantly (P<0.0001) greater than that for the scalpel (38.8+/
      7.2 microm). If macroscopically and microscopically non-degenerate, then human
      lateral femoral condylar cartilage from the anterior cut of knee resections has
      normal biophysical parameters (water content and lack of swelling on excision).
      The surgical harvester (Acufex), used in human osteochondral grafting, caused a
      substantial margin of cell death at the periphery of the graft, and the SZ
      appeared to be especially vulnerable. This effect may be important in terms of
      limiting the reparative capacity of the SZ. The harmful effect on viability is
      likely to impede lateral repair which is fundamental to subsequent structural and
      functional integrity.

PMID- 15726498
TI  - Position effects due to chromosome breakpoints that map approximately 900 Kb
      upstream and approximately 1.3 Mb downstream of SOX9 in two patients with
      campomelic dysplasia.
AB  - Campomelic dysplasia (CD) is a semilethal skeletal malformation syndrome with or
      without XY sex reversal. In addition to the multiple mutations found within the
      sex-determining region Y-related high-mobility group box gene (SOX9) on 17q24.3,
      several chromosome anomalies (translocations, inversions, and deletions) with
      breakpoints scattered over 1 Mb upstream of SOX9 have been described. Here, we
      present a balanced translocation, t(4;17)(q28.3;q24.3), segregating in a family
      with a mild acampomelic CD with Robin sequence. Both chromosome breakpoints have
      been identified by fluorescence in situ hybridization and have been sequenced
      using a somatic cell hybrid. The 17q24.3 breakpoint maps approximately 900 kb
      upstream of SOX9, which is within the same bacterial artificial chromosome clone
      as the breakpoints of two other reported patients with mild CD. We also report a
      prenatal identification of acampomelic CD with male-to-female sex reversal in a
      fetus with a de novo balanced complex karyotype, 46,XY,t(4;7;8;17)(4qter-
      >4p15.1::17q25.1-->17qter;7qter-->7p15.3::4p15.1-->4pter;8pter-->8q12.1::7p15.3-
      >7pter;17pter-->17q25.1::8q12.1-->8qter). Surprisingly, the 17q breakpoint maps
      approximately 1.3 Mb downstream of SOX9, making this the longest-range position
      effect found in the field of human genetics and the first report of a patient
      with CD with the chromosome breakpoint mapping 3' of SOX9. By using the
      Regulatory Potential score in conjunction with analysis of the rearrangement
      breakpoints, we identified a candidate upstream cis-regulatory element, SOX9cre1.
      We provide evidence that this 1.1-kb evolutionarily conserved element and the
      downstream breakpoint region colocalize with SOX9 in the interphase nucleus,
      despite being located 1.1 Mb upstream and 1.3 Mb downstream of it, respectively.
      The potential molecular mechanism responsible for the position effect is
      discussed.

PMID- 15726500
TI  - Colorectal cancer: looking forward.

PMID- 15726501
TI  - Screening for colorectal cancer--now and the near future.
AB  - When used appropriately, screening for colorectal cancer (CRC) can reduce disease
      related morbidity and mortality. Current methods include fecal occult blood
      testing (FOBT), flexible sigmoidoscopy [FS], barium enema, and colonoscopy; all
      are cost-effective techniques. Unfortunately, offering an array of options has
      not increased screening utilization, which continues to lag behind that of other
      common cancers. Newer techniques, particularly virtual colonoscopy (VC) and stool
      DNA testing, may offer attractive alternatives for healthcare provider
      recommendation and patient use.

PMID- 15726502
TI  - Genetics of hereditary colorectal cancer.
AB  - Genetic factors can dramatically influence the risk of colorectal cancer, and the
      molecular bases of many hereditary colorectal cancer syndromes, including
      familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and hereditary
      nonpolyposis colorectal cancer (HNPCC) have been elucidated. Additional syndromes
      continue to be defined as new genes, including MYH , are linked to the
      development of colonic polyps and cancer. The risks of colorectal cancer are
      variable and depend on the specific germline alterations. Some mutations are
      associated with a 100% lifetime risk of developing cancer, while others are
      associated with only a mild increase in risk. Although there are overlapping
      clinical features in many of these syndromes, they can be distinguished by the
      age at cancer diagnosis, inheritance pattern, number and distribution of polyps,
      specific histologic features of the cancers, and the presence of distinctive
      extracolonic features. The introduction and refinement of genetic testing has
      provided a new and invaluable tool for the diagnosis and assessment of cancer
      risk for suspected cases of hereditary colon cancer.

PMID- 15726503
TI  - Colorectal cancer prevention: is an ounce of prevention worth a pound of cure?
AB  - Colorectal cancer (CRC) is among the most common human malignancies and remains a
      leading cause of cancer-related morbidity and mortality. Colorectal
      carcinogenesis is a multistep process characterized by molecular and cellular
      alterations that result in an identifiable precursor lesion, ie, the adenomatous
      polyp. The transition from normal mucosa to adenoma and its subsequent
      progression to carcinoma are protracted events that offer opportunities for
      preventive interventions. Suppression or reversal of the carcinogenic process in
      the colorectum with nonpharmacologic or pharmacologic agents, ie,
      chemoprevention, is an area of considerable research interest and activity.
      Interest in this field derives from multiple epidemiologic studies showing that
      regular and continued use of nonsteroidal anti-inflammatory drugs (NSAIDs),
      predominantly aspirin, is associated with significant reductions in both
      colorectal adenoma and carcinoma incidence. NSAIDs were first shown to be
      effective in patients with familial adenomatous polyposis (FAP). Subsequent
      randomized trials in FAP demonstrated that sulindac and the selective
      cyclooxygenase-2 (COX-2) inhibitor, celecoxib, can significantly regress existing
      adenomas, and resulted in Food and Drug Administration (FDA) approval of
      celecoxib for adjunctive management of these patients. Based on the
      aforementioned data, aspirin and coxibs have been or are currently being
      evaluated for the prevention of sporadic adenoma recurrence in high-risk patient
      populations. Evidence indicates that aspirin can reduce adenoma recurrence rates
      in patients with prior colorectal neoplasia; however, questions remain, including
      the optimal dosage, timing of initiation and duration of treatment, and clinical
      benefit versus potential harm to patients. These same issues apply to the
      nonpharmacologic agents such as calcium, folic acid, and selenium given as
      dietary supplements. Apart from aspirin, calcium carbonate is the only other
      agent that has been shown to modestly reduce sporadic adenoma recurrence rates in
      a randomized trial. Folate and selenium are being actively studied based on
      provocative preclinical data. In addition to demonstrating efficacy,
      chemopreventive agents must also be safe for long-term use, be well accepted by
      patients, and be cost-effective. In this review, the current status of CRC
      chemoprevention will be discussed, including the available evidence for selected
      pharmacologic and nonpharmacologic agents, particularly among high-risk
      populations.

PMID- 15726504
TI  - Chemotherapy for advanced colorectal cancer: let's not forget how we got here
      (until we really can).
AB  - Physicians and patients alike have been heartened by the recent advances in the
      treatment of colorectal cancer. The emergence of novel agents that are active in
      the treatment of this devastating disease, such as cetuximab and bevacizumab, has
      been particularly notable. However, even before these recent events, a
      substantial change in prognosis for patients with metastatic colorectal cancer
      had occurred as a result of advances in traditional chemotherapeutic agents.
      Refinements in dose, schedule, and sequence continue to be made that could lead
      to further improvements in outcomes. Additionally, new chemotherapeutic agents
      with promise for activity in colorectal cancer are being studied. Chemotherapy is
      likely to remain a central element of the treatment strategy. Our understanding
      of its current role is discussed in this article.

PMID- 15726505
TI  - Oral capecitabine: bridging the Atlantic divide in colon cancer treatment.
AB  - 5-Fluorouracil (5-FU) plus leucovorin (LV) has been the mainstay of treatment for
      colorectal cancer (CRC), with infused schedules more widely adopted in Europe and
      bolus schedules preferred in North America. However, the effective, oral
      fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV
      on both sides of the Atlantic. Capecitabine generates 5-FU preferentially in
      tumor and is a well-established, first-line treatment for metastatic CRC. In this
      setting, capecitabine achieves a superior response rate, at least equivalent time
      to disease progression (TTP) and overall survival, and favorable safety compared
      with bolus 5-FU/LV. The benefits of capecitabine have been transfered into the
      adjuvant setting. Recent data from a large, international, randomized trial
      (Xeloda Adjuvant Chemotherapy Trial [X-ACT]) confirm that capecitabine (Xeloda,
      Roche Laboratories, Nutley, NJ) achieves favorable safety versus 5-FU/LV (Mayo
      Clinic regimen) and is at least as effective as IV 5-FU/LV in the adjuvant
      treatment of patients with resected stage III colon cancer. Capecitabine is also
      an effective and well-tolerated combination partner for oxaliplatin (XELOX) and
      irinotecan (XELIRI), achieving high efficacy with a good safety profile. An
      extensive phase III clinical trial program is further establishing the potential
      of the simplified capecitabine combinations to improve outcomes and unify
      treatment practices in the metastatic and adjuvant settings. New combinations
      with novel agents such as capecitabine/oxaliplatin plus erlotinib or bevacizumab
      are currently under investigation. Capecitabine has also shown promising activity
      and good tolerability in combination with radiotherapy in rectal cancer.

PMID- 15726506
TI  - The epidermal growth factor receptor as a target for colorectal cancer therapy.
AB  - The epidermal growth factor receptor (EGFR) is the prototypical member of the
      erbB receptor family. The EGFR axis is activated by a variety of ligands that are
      crucial in the formation and propagation of many tumors, including colorectal
      cancer, through their effects on cell signaling pathways, cellular proliferation,
      control of apoptosis, and angiogenesis. The importance of the EGFR axis in
      tumorigenesis and tumor progression makes it an attractive target for the
      development of anticancer therapies. A variety of targeting strategies to exploit
      the role of EGFR in tumors have been employed. The most highly developed of these
      anti-EGFR approaches are the monoclonal antibodies and the tyrosine kinase
      inhibitors (TKIs). Clinical evaluations of these compounds have yielded some
      promising results. The role of the EGFR axis in colorectal cancer formation and
      progression is reviewed and the clinical development of these anticancer EGFR
      targeted drugs is reviewed and updated.

PMID- 15726507
TI  - Targeting vascular endothelial growth factor and angiogenesis for the treatment
      of colorectal cancer.
AB  - Angiogenesis, the development and proliferation of new blood vessels, is critical
      for the growth of tumors. The process of new blood vessel formation is under
      complex control from a variety of pro- and anti-angiogenesis factors. By
      identifying and understanding these factors, new therapies have been developed to
      inhibit tumor growth and survival by blocking tumor-related angiogenesis. Recent
      success with the monoclonal antibody against vascular endothelial growth factor
      (VEGF; bevacizumab) in a large, randomized, phase III study has provided a
      critical proof of principle for this therapeutic area. This review will outline
      the biology of angiogenesis in colorectal cancer and discuss the current status
      of angiogenesis inhibition in its treatment.

PMID- 15726508
TI  - Cyclooxygenase-2 inhibition in colorectal cancer: boom or bust?
AB  - Currently, combination chemotherapy represents the standard of care treatment for
      patients with metastatic colorectal cancer in the United States. Despite recent
      improvements with the addition of biologic agents, novel treatment approaches are
      needed to further benefit patients. Cyclooxygenase (COX)-2 inhibition represents
      one such possibility. COX-2 is highly expressed in colorectal tumor
      neovasculature and nodal and liver metastases, and expression of COX-2 correlates
      with tumor stage and patient survival in selected series. COX-2 may be related to
      colorectal cancer development and propagation through multiple mechanisms,
      including stimulation of growth, migration, and invasiveness, resistance to
      apoptosis, and enhancement of angiogenesis. Epidemiologic data suggest
      nonsteroidal anti-inflammatory drugs (NSAIDs) might prevent development of
      colorectal cancers, and preclinical data suggest selective COX-2 inhibitors might
      be additive or synergistic with specific chemotherapeutic agents used in the
      treatment of colorectal cancer. Despite the lack of published phase I data and
      the limited, preliminary results of phase II studies, combinations of celecoxib
      and standard colorectal cancer chemotherapy have entered randomized trials. It is
      too early to definitively state whether COX-2 inhibition represents a major
      breakthrough in the treatment of colorectal cancer. Pending the results of
      ongoing and planned phase III studies, use of COX-2 inhibitors as single agents
      or incorporation of COX-2 inhibition into combined modality therapy of colorectal
      cancer should be limited to the setting of clinical trials.

PMID- 15726509
TI  - Colorectal cancer vaccines: what we know and what we don't yet know.
AB  - Humans have a sophisticated immune system that functions to clear invading
      organisms and abnormal cells. However, cancers are able to arise despite this
      immune system. Vaccines have the potential of benefiting cancer patients by
      stimulating an immune response against tumor-associated antigens (TAA). Our
      enhanced understanding of how the immune system processes and presents antigens
      has allowed an array of vaccine modalities to be developed and tested. The TAA
      with the greatest number of vaccine platforms tested in colorectal cancer is
      carcinoembyronic antigen (CEA). Trials to date have demonstrated safety and
      evidence for the induction of an immune response against CEA. This article will
      review trials conducted with a variety of CEA vaccines. Most studies conducted
      are phase I or II in the metastatic disease setting, limiting our understanding
      of the role of the immune response in controlling colon cancers. Phase III trials
      conducted to date have conflicting data with respect to improvements in disease
      free and overall survival. It is our challenge to determine if and which vaccines
      have sufficient benefit to warrant large-scale trials in the adjuvant and
      prevention settings.

PMID- 15726510
TI  - Liver-directed therapies in colorectal cancer.
AB  - The liver is the most common site of metastatic colorectal cancer (CRC) and the
      status of this organ is an important determinant of overall survival in patients
      with advanced disease. Complete resection of hepatic CRC metastases can provide a
      long-term cure for some patients, but the majority of liver metastases are not
      amenable to such surgery. Furthermore, most patients after curative resection
      ultimately suffer from recurrence, and the majority of such failures occur in the
      liver. Various ablative techniques can achieve local control of tumor after
      incomplete resection or for palliation. Tumor ablation currently has a secondary
      therapeutic role, as there is no evidence that it can achieve long-term survival
      comparable to surgical resection. Regional chemotherapy delivers tumoricidal
      agents in a selective fashion, minimizing systemic toxicity and damage to normal
      liver cells. Chemotherapy agents delivered through the hepatic artery can extend
      time to liver recurrence after curative resection and may prolong survival both
      in the adjuvant setting and when given to patients with unresectable disease.
      Molecular-based therapies, such as gene delivery and oncolytic viruses, provide
      promise for curative outcomes in patients with advanced disease.

PMID- 15726511
TI  - Adjuvant therapy of colon cancer.
AB  - Although surgical resection is still the only curative maneuver in the treatment
      of colon cancer, efforts of the past decades have proved that systemic
      chemotherapy in the adjuvant setting definitely improves the curative rate for
      those patients with localized colon cancer. The combination of the 5-fluorouracil
      (5-FU) and leucovorin (LV) remains the reference treatment. However, the
      advantage of infusional 5-FU/LV with oxaliplatin (FOLFOX) as adjuvant treatment
      may change the paradigm soon. Capecitabine may be considered as an alternative to
      5-FU/LV in the adjuvant therapy of stage III colon cancer. The clinical benefit
      of adjuvant chemotherapy for localized node negative (stage II) disease is
      definite but small, even though there is yet no universal consensus. Novel
      molecular and biologic-oriented agents are being studied. Further analysis and
      definition of prognostic and predictive markers may allow future adjuvant therapy
      to be individualized.

PMID- 15726512
TI  - Combined modality treatment for rectal cancer.
AB  - Significant gains have been achieved in the integration of radiation therapy (RT)
      and chemotherapy with surgery in the management of patients with localized rectal
      cancer. Treatment combinations of RT and chemotherapy with surgery have evolved
      to neoadjuvant approaches of these modalities to enhance sphincter preservation,
      tumor control, and reduction of acute and late treatment-related morbidity.
      Although 5-fluorouracil (5-FU)-based chemotherapy in combination with RT remains
      the standard adjuvant therapy for rectal cancer, the integration of novel
      chemotherapeutic agents and biologic modulators is being actively investigated.

PMID- 15726513
TI  - Pharmacogenetic influences on treatment response and toxicity in colorectal
      cancer.
AB  - Current use of chemotherapeutic and targeted agents for advanced colorectal
      cancer (CRC) results in high tumor response rates and relatively long overall
      patient survival. Fluoropyrimidines, irinotecan, and oxaliplatin are highly
      active in first-line and salvage therapy of colorectal cancer. Targeted
      therapies, including anti-angiogenesis agents and anti-epidermal growth factor
      receptor antibodies, have been incorporated with traditional chemotherapy and
      offer additional options for patients with CRC. However, there is marked
      variability in response to therapy, as well as frequency and severity of
      toxicities. Molecular markers and pharmacogenomic profiling may improve
      prediction of patients who will experience significant benefit or toxicity from
      currently available agents. Validation of these predictive factors in prospective
      clinical trials is now necessary to allow for a rational and systematic
      individualization of cancer therapy.

PMID- 15726514
TI  - Intratumoral molecular or genetic markers as predictors of clinical outcome with
      chemotherapy in colorectal cancer.
AB  - Identification of molecular markers at either the intragenic, chromosomal, mRNA,
      or protein level that might predict whether colorectal cancer patients are likely
      to benefit from adjuvant or palliative therapy is a high priority. The majority
      of clinical studies addressing this issue, particularly those done in the
      adjuvant setting, analyzed tumor samples from patients treated in the era when 5
      fluorouracil (5-FU) alone or combined with leucovorin or levamisole were the
      mainstay of therapy. This review highlights some of the intratumoral molecular
      markers that may have importance as predictors of benefit with 5-FU-based
      therapy. Although the goal of these investigations is to one day permit selection
      of therapy for an individual patient based on the tumor phenotype, prospective
      studies have yet to be conducted that test whether selection of therapy based on
      molecular markers results in an improved outcome.

PMID- 15726515
TI  - The evaluation of amifostine for mucosal protection in patients with advanced
      loco-regional squamous cell carcinomas of the head and neck (SCCHN) treated with
      concurrent weekly carboplatin, paclitaxel, and daily radiotherapy (RT).
AB  - Concurrent chemotherapy and radiation has improved the outcome for patients
      presenting with locally advanced squamous cell carcinomas of the head and neck
      (SCCHN). These improvements have come at a cost of increased treatment-related
      toxicities. We previously reported the results of a phase II trial examining the
      role of concurrent carboplatin, paclitaxel, and daily radiotherapy (RT) in SCCHN.
      In an attempt to decrease these side effects, we conducted a prospective phase II
      trial evaluating the role of amifostine (Ethyol, MedImmune Oncology, Inc,
      Gaithersburg, MD) in patients treated with this concurrent chemoRT scheme. From
      April 2002 to September 2004, 19 patients with stage III-IV SCCHN were enrolled
      on a prospective phase II trial. Treatment consisted of daily RT delivered to
      70.2 Gy (1.8 Gy/fx) with amifostine 500 mg IV (<1 hour before RT), and concurrent
      weekly carboplatin (100 mg/m2) and paclitaxel (40 mg/m2). Median age was 58.5
      years (range, 48 to 70 years); male to female ratio was, 83%:17%; Caucasian
      versus other was, 61%/39%. Tumor characteristics based on histology were: primary
      cancers of the oropharynx (55.6%); supraglottic larynx (16.7%); hypopharynx
      (16.7%); oral cavity (5.6%); and unknown primaries (5.6%). All patients presented
      with locally advanced, unresectable disease T4 (50%), T3 (27.8%), and advanced
      nodal disease (N2b-N3) (78%). Toxicities were measured weekly during treatment
      and at each follow-up visit. Disease response to therapy was determined 2 months
      after completion of therapy. Seventeen patients are evaluable for response and
      survival at 2 months following completion of RT. Eighty-four percent completed
      the prescribed radiation treatment, and 84% of patients received more than six
      cycles of chemotherapy. The median number of missed chemotherapy cycles was 1.5
      (range, 0 to 5 cycles). Fifty-six percent of patients received more than 90% of
      prescribed amifostine doses, with chemoRT-related toxicity being the most common
      reason for withholding the dose (77%). Median doses of missed amifostine were
      three (range, 0 to 30 doses). Grade 3 toxicities associated with therapy were:
      mucositis and dysphagia (40% of patients each), dehydration (27%), xerostomia
      (20%), and dermatitis (20%); 53% of patients experienced grade 3 leukopenia,
      while grade 3/4 neutropenia developed in 20%/13%. No grade 4/5 nonhematologic
      toxicities were encountered. Forty percent of patients completed RT without
      unscheduled treatment breaks secondary to treatment-related toxicity. Median
      treatment-break time was 5 days (range, 0 to 20 days). Clinical complete response
      at both the primary site of disease and neck was achieved in 75% of patients 2
      months following completion of RT. Weekly carboplatin and paclitaxel administered
      concurrently with definitive RT and daily amifostine is well tolerated, with over
      85% of patients completing therapy with acceptable toxicity. The addition of
      amifostine appears to decrease treatment-related toxicity without impacting
      efficacy.

PMID- 15726516
TI  - Toxicity and compliance of subcutaneous amifostine in patients undergoing
      postoperative intensity-modulated radiation therapy for head and neck cancer.
AB  - Standard conventional radiation therapy for advanced head and neck tumors
      typically involves administering high radiation dose to the major salivary glands
      bilaterally. In most cases, this causes a marked reduction in oral saliva output.
      Xerostomia is one of the most prevalent late side effects of radiation for head
      and neck malignancies, and patients cite it as the major cause of decreased
      quality of life. The degree of xerostomia has been reported to depend on the
      radiation dose and volume of salivary gland irradiated. Several studies show dose
      volume-response relationships in the salivary glands, suggesting the possibility
      of significant improvement in saliva production postradiation, as well as quality
      of life, if radiation techniques can spare the salivary glands. A growing body of
      literature supports the premise that intensity-modulated radiation therapy (IMRT)
      allows irradiation of tumor targets in the head and neck while sparing
      substantial portions of salivary glands. Early clinical experience has shown
      substantial sparing of salivary flow following IMRT, and suggests at least equal
      tumor control but improved xerostomia compared with patients receiving standard
      radiation techniques. We hypothesize that the addition of a radiation protector,
      such as amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) may further improve
      salivary function over that obtained with IMRT alone. To test this hypothesis, we
      have initiated a pilot clinical trial to compare unstimulated and stimulated
      salivary flow rates 6 months and 1 year after IMRT + amifostine with historic
      controls treated with IMRT alone. Twenty-seven patients have been accrued onto
      this trial, and the toxicity and compliance data are reported herein.

PMID- 15726518
TI  - A randomized phase II trial of amifostine for head and neck irradiation in
      lymphoma.
AB  - Acute and long-term oral complications occur in patients receiving mantle
      radiation therapy or irradiation to the head and neck region for Hodgkin's
      disease or non-Hodgkin's lymphoma. While considerable data are available on the
      effect of radiation therapy on the oral function and quality of life of patients
      with squamous cell carcinoma of the head and neck, such information is lacking
      for similarly irradiated lymphoma patients. In this article we discuss the
      rationale and study design of an ongoing, randomized phase II study evaluating
      the role of amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) as a radiation
      protectant in patients receiving head and neck irradiation for lymphoma. Further
      investigation in this lymphoma population is needed to improve our understanding
      of the extent of the problem and its impact on patients' daily living and
      functioning. Importantly, fine-tuning the treatment and management approaches to
      minimize morbidity while maximizing the survival and quality of life of patients
      are crucial next steps.

PMID- 15726517
TI  - Selective dose escalation of chemoradiotherapy for esophageal cancer: role of
      treatment intensification.
AB  - This ongoing phase II study is designed to assess the outcomes (survival and
      failure patterns) of therapy for localized esophageal cancer with conventional
      dose radiation (50.4 Gy) with concurrent continuous infusion 5-fluorouracil (5
      FU) and weekly carboplatin/paclitaxel. Patients with less than complete response
      or partial response received dose escalation of radiation to 59.4 Gy with the
      same chemotherapy. This report details the results of the first 18 patients
      treated. From July 2000 to June 2003, we prospectively enrolled 18 patients with
      T1-4, N0-1, M0-1a esophageal carcinoma to receive paclitaxel 45 mg/m 2
      intravenously over 1 hour and carboplatin AUC 2 intravenously over 30 minutes on
      days 1, 8, 15, 22, 29, and 36. 5-Fluorouracil 225 mg/m2 was delivered as a
      continuous infusion on days 1 through 38. Radiation therapy was given 1.8 Gy x 5
      days/week x 5.5 weeks (50.4 Gy in 28 fractions). After 6 to 8 weeks, patients
      underwent repeat staging with computed tomography scan, endoscopic ultrasound,
      and biopsy. Patients with a positive biopsy, or less than partial response by
      computed tomography and endoscopic ultrasound, received a boost of 9 Gy with the
      same concurrent chemotherapy. Patients were followed every 4 months with computed
      tomography/endoscopic ultrasound the first year and every 6 months thereafter.
      Median follow-up was 19 months. Eleven of 18 patients (61.1%) attained a complete
      response/partial response; six of 18 (33.3%) received a boost. Overall survival
      was 30% at 3 years, with a median of 25 months. Patients with less than 10%
      pretreatment weight loss had an overall survival of 36% with a median of 26
      months. In patients with more than 10% pretreatment weight loss, median survival
      was 14 months with 0% surviving at 2 years. Local/regional control was 67% (no
      boost patients [78%]; boost patients [40%]). Progression-free survival was 31% at
      3 years, with a median of 14 months. Distant metastasis-free survival was 40% at
      3 years, with a median of 27 months. Seventy-nine percent of patients required at
      least one dose reduction in chemotherapy because of toxicities. Radiation delays
      ranged from 0 to 62 days, with a median of 7 days. Grade 2/3 acute esophagitis
      was experienced by 89% and 39% of patients, respectively; 28% of patients
      developed esophageal strictures requiring dilatations. The combination of
      continuous-infusion 5-FU and weekly carboplatin/paclitaxel with selective
      radiation dose escalation yields promising results without surgery and adjuvant
      chemotherapy. The toxicities of therapy, while manageable, were significant.

PMID- 15726519
TI  - A phase II study to assess the efficacy of amifostine for
      submandibular/sublingual salivary sparing during the treatment of head and neck
      cancer with intensity modulated radiation therapy for parotid salivary sparing.
AB  - Intensity modulated radiation therapy (IMRT) allows for relative parotid salivary
      gland sparing for patients undergoing treatment for head and neck squamous cell
      cancer, but is less reliable for sparing the submandibular glands. Cytoprotection
      with amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) has been shown to
      decrease rates of acute and late xerostomia in patients undergoing radiation
      therapy for head and neck squamous cell cancer. The addition of amifostine to
      IMRT may augment parotid salivary sparing, and add submandibular/sublingual, and
      minor salivary gland sparing resulting in greater salivary flow rates and a more
      physiologic saliva. Eligible patients include those slated to receive definitive
      IMRT for early oropharynx cancer or postoperative RT, both without chemotherapy,
      for more advanced cancers. These include T1, T2 and favorable T3 (favorable,
      exophytic), N0-2b (small volume) M0 oropharynx cancers who are to receive
      bilateral neck RT. Postoperative patients with nodal metastases, T3 and T4
      primaries, perineural invasion, and lymphovascular invasion will be eligible.
      Patients will receive 30 to 33 fractions. Clinical target volume (CTV) 1 will
      receive 60 to 66 Gy, CTV2 will receive 60 Gy, and CTV3 will receive 54 to 57 Gy.
      The mean dose goal for the parotid gland is 25 Gy. Patients will receive fixed
      dose amifostine 500 mg subcutaneously 30 to 60 minutes before each radiation
      fraction. Subjective xerostomia questionnaires will be administered. Whole mouth
      and individual major salivary gland stimulated and unstimulated saliva will be
      collected before and after therapy at 6 weeks, 6 and 12 months. Xerostomia
      outcomes will be correlated with salivary dose volume histogram data. Accrual has
      not yet begun. The results of this study will give an indication of the objective
      and subjective benefit of combined IMRT physical parotid salivary sparing and
      amifostine chemical cytoprotection for combined salivary gland sparing and
      reduction in the rate of xerostomia in patients undergoing IMRT for head and neck
      squamous cell cancer.

PMID- 15726520
TI  - Radiotherapy-induced salivary dysfunction.
AB  - Dry mouth (xerostomia) is one of the most common complaints following radiation
      therapy (RT) for head and neck cancers. Notably, RT causes irreparable damage to
      salivary glands that increases the risk for severe and long-term oral and
      pharyngeal disorders. Several strategies in the treatment of head and neck
      cancers have been developed to prevent RT-induced salivary dysfunction while
      providing definitive oncologic therapy. These include salivary-sparing RT;
      cytoprotectants (such as amifostine); combination therapy of high-dose-rate
      intraoperative RT, external beam RT, plus a cytoprotectant; salivary gland
      surgical transfer; and gene therapy. Future research that incorporates biologic,
      pharmacologic, and technologic advancements that optimize therapeutic ratios and
      minimizes adverse oral sequelae is warranted.

PMID- 15726521
TI  - The role of amifostine in the treatment of carcinoma of the uterine cervix: an
      update of RTOG-0116 and review of future directions.
AB  - Approximately 10,520 women will be diagnosed with carcinoma of the uterine cervix
      in 2004, resulting in significant mortality. While definitive or adjuvant
      radiation therapy remains a critical component of treatment, both local and
      distant recurrences may occur. The recent addition of chemotherapy has helped
      reduce these recurrences and improve survival, albeit at a cost of increased
      toxicity, especially in patients requiring extended-field treatment. New agents,
      such as amifostine (Ethyol, MedImmune Inc, Gaithersburg, MD), that possess
      cytoprotective and radioprotective properties may help ameliorate toxicity. This
      report reviews and updates the rationale and current experience with amifostine
      in the treatment of carcinoma of the uterine cervix. Data suggest a benefit in
      patients with pelvic malignancies receiving amifostine before either chemotherapy
      or radiation, and that subcutaneous administration may be as efficacious and less
      toxic than the intravenous route. Ongoing trials will likely provide more data to
      the role of amifostine in the treatment of carcinoma of the uterine cervix, and
      especially whether the administration of subcutaneous amifostine before both
      chemotherapy/radiation therapy will translate into a reduction in acute and late
      toxicity.

PMID- 15726522
TI  - Open label multicenter trial of subcutaneous amifostine (Ethyol) in the
      prevention of radiation induced esophagitis and pneumonitis in patients with
      measurable, unresectable non-small cell lung cancer.
AB  - While concurrent delivery of chemotherapy and radiotherapy (RT) has a synergistic
      effect on tumor control and improves the median and overall survival in patients
      with locally advanced non-small cell lung cancer, appreciable acute and late
      morbidity occur to the esophagus and the lung during treatment (ie, acute
      radiation esophagitis, pulmonary toxicity). Emerging evidence suggests that the
      volume of normal lung exposed to certain threshold doses of RT might predict for
      the incidence of pneumonitis. Clinical data also indicate that amifostine
      (Ethyol; Medimmune Inc, Gaithersburg, MD), an organic thiophosphate, acts as a
      selective cytoprotective agent for normal tissues against the toxicities of
      chemotherapy and RT. Moreover, preclinical and clinical data suggest that
      subcutaneous administration of amifostine may be better tolerated with similar
      efficacy to that of the intravenous route. We are conducting an open-label trial
      that is accruing patients with locally advanced non-small cell lung cancer, who
      will receive concurrent chemoradiotherapy (cisplatin/etoposide or
      carboplatin/paclitaxel plus RT delivered using 3-dimensional conformal
      radiotherapy treatment planning) and amifostine 500 mg before RT. Incidence and
      severity of acute radiation esophagitis, acute radiation pneumonitis, chronic
      radiation pneumonitis, and changes in pulmonary function will be recorded, as
      will elements of the RT treatment planning (eg, dose volume histogram data for
      the lung and esophagus). Pre- and post-therapy pulmonary function is a primary
      endpoint, and others include general safety assessments of subcutaneous
      amifostine administration.

PMID- 15726523
TI  - Randomized phase II study of amifostine mucosal protection by either subcutaneous
      injection or rapid IV bolus for patients with inoperable stage II-IIIA/B or stage
      IV non-small cell lung cancer with oligometastases receiving concurrent
      radiochemotherapy with carboplatin and paclitaxel followed by optional
      consolidative chemotherapy: a follow-up study after RTOG 98-01.
AB  - While concurrent chemoradiotherapy is a standard treatment for good-performance
      patients with non-small cell lung cancer, acute esophagitis is a frequent
      toxicity. The incidence of severe acute esophagitis > or = grade 3 in patients
      treated with standard (once-daily) radiation therapy alone is 1.3%, increasing to
      14% to 25% with the addition of concurrent chemotherapy, and 24% to 34% for the
      combination of hyperfractionated (twice-daily) radiation therapy plus concomitant
      chemotherapy. Although esophagitis is almost never a cause of mortality, it
      results in significant morbidity and may force treatment breaks, which are
      associated with inferior outcome in non-small cell lung cancer. Substantial
      investigative efforts to prevent or ameliorate esophagitis have been conducted.
      We describe herein the rationale/study design for a multi-institutional, phase II
      randomized study to evaluate either daily subcutaneous or intravenous bolus
      infusions of amifostine in patients with non-small cell lung cancer who receive
      standard fractionated thoracic radiation therapy concurrently with weekly
      paclitaxel and carboplatin chemotherapy.

PMID- 15726524
TI  - Can the use of amifostine improve cure rates for patients with advanced non-small
      cell lung cancer?
AB  - Concurrent chemoradiation, probably plus systemic chemotherapy, currently offers
      the best treatment strategy in stage IIIA/IIIB non-small cell lung cancer.
      However, such approaches do not control local disease well, perhaps because of
      inadequate radiation dose. While few studies have explored higher than standard
      radiation doses (ie, 60 Gy), the major fear is that higher doses increase patient
      morbidity without improving cure rates. A University of North Carolina (Chapel
      Hill, NC) phase I/II trial suggests that at least 74 Gy can be given safely to
      patients with cytotoxic drugs, with a suggestion of improved survival. Moreover,
      other trial data have suggested that the cytoprotective and radioprotective agent
      amifostine can be used to reduce esophagitis and possibly pneumonitis in patients
      treated with conventional radiation doses. We describe herein a proposed clinical
      trial designed to test: (1) the hypothesis that higher radiation doses can lead
      to a survival advantage in patients with non-small cell lung cancer, and (2) the
      value of amifostine as a cytoprotective agent in the high-radiation dose range.

PMID- 15726525
TI  - Phase I study for poor-prognosis lymphoma: augmentation of the "BEAM" regimen
      with escalating dose melphalan using amifostine cytoprotection and autologous
      hematopoietic stem cell transplantation--a preliminary report.
AB  - We and others have previously shown that the use of amifostine (Ethyol; MedImmune
      Inc, Gaithersburg, MD) can ameliorate certain regimen-related toxicities of high
      dose melphalan (HD-MEL) in the autologous hematopoietic stem cell transplant
      setting. Our recent experience indicated that the maximum tolerated dose of HD
      MEL plus autologous hematopoietic stem cell transplant could be increased from
      approximately 200 mg/m2 to at least 280 mg/m2 with amifostine. Although a dose
      limiting toxicity was not clearly identified, atrial fibrillation was noted in
      several patients. Phase II trials using this regimen have been reported in
      lymphoma and myeloma. Nonetheless, it is unlikely that single agent therapy,
      regardless of dose, will be highly curative in advanced hematologic malignancy.
      Thus, we used amifostine to permit dose escalation of HD-MEL within the BEAM
      (BCNU/etoposide/arabinosylcytosine/HD-MEL) combination chemotherapy regimen
      before autologous hematopoietic stem cell transplant in selected patients with
      lymphoma. Patient entry at the starting dose (ie, HD-MEL 140 mg/m2) has been
      completed without the development of severe regimen-related toxicities. This
      trial is ongoing.

PMID- 15726526
TI  - Randomized trials of amifostine and radiotherapy: effect on survival?
AB  - Amifostine (Ethyol; MedImmune Inc, Gaithersburg, MD) is a cytoprotective and
      radioprotective agent for normal tissues against the deleterious effects of
      chemotherapeutic agents and/or ionizing radiation. We have compiled a unique
      database for meta-analysis that aims to address the controversial concept of the
      tumor protection. The proposed meta-analysis on survival outcome, which is based
      on individual patient data, will be more useful than literature-based meta
      analyses because of the superiority of reliable, longer follow-up patient data.
      It will be also possible to study the effect(s) of amifostine in different tumor
      types.

PMID- 15726527
TI  - Cytoprotection in acute myelogenous leukemia (AML) therapy.
AB  - Planning therapy for acute myelogenous leukemia (AML) is difficult because of the
      heterogeneous nature of the disease and varying patient age at presentation.
      Cytogenetics and patient age at the time of diagnosis are two major factors
      determining treatment outcome in AML. Patients with poor-risk cytogenetics have
      much lower complete remission rates than other groups. In addition, AML in
      patients greater than 55 to 60 years of age often exhibits a resistant phenotype,
      more akin to secondary AML or AML arising from myelodysplastic syndromes. This
      group is also characterized by lower complete remission rates, and often requires
      the delivery of intensive therapy to a patient population that is the least
      likely to tolerate it. At the Jefferson Health System (Philadelphia, PA), we
      wished to develop a regimen that was maximally intensive to treat stubborn
      disease, but gentle enough to be given to all patients regardless of age. Toward
      this end, 33 patients received a maximal dose of the cytoprotective agent,
      amifostine, before each infusion of idarubicin in the "7 + 3" regimen, escalating
      the dose of idarubicin in a phase I fashion to a maximum dose of 24 mg/m2 . The
      data indicate that the addition of amifostine to "7 + 3" AML induction therapy
      enables a substantial escalation of the idarubicin dose through the 21-mg/m2 dose
      level, without a concomitant increase in side effects, thus providing a regimen
      that is both intensive and applicable to patients of all ages. Currently, phase
      II studies are ongoing on a national basis to evaluate the efficacy of this
      regimen.

PMID- 15726528
TI  - Preclinical perspectives on the use of platinum compounds in cancer chemotherapy.
AB  - Although platinum compounds have long been used in cancer chemotherapy,
      understanding the biochemistry and specific activity of these agents remains a
      focus of ongoing research, particularly with regard to next-generation platinum
      agents. This review will examine current knowledge and recent studies of the
      molecular mechanisms of platinum DNA damage and repair, including novel platinum
      DNA targets. Gene expression associated with platinum DNA damage will also be
      explored, as well as mechanisms of platinum-drug delivery, drug resistance, and
      future directions in the development of novel platinum agents.

PMID- 15726529
TI  - Recent updates in the clinical use of platinum compounds for the treatment of
      gastrointestinal cancers.
AB  - Since the late 1970s, clinical researchers have investigated the use of platinum
      compounds administered as single agents or in combination with other drugs for
      the treatment of a variety of cancers, including gastrointestinal cancers. After
      extensive clinical development, oxaliplatin has become an important option in the
      treatment of colorectal cancer, and its role in the treatment of other
      gastrointestinal cancers (and other cancers) remains a focus of intense
      investigation. Historically, platinum compounds have shown limited single-agent
      activity in pancreatic cancer, although more recent studies have explored
      potential synergies using platinum-based combinations. In addition, platinum
      agents have long been used in the treatment of advanced gastroesophageal tumors
      (typically 5-fluorouracil and cisplatin combinations), although poor outcomes in
      this disease clearly indicate a need for the development of more active agents.
      This review will examine recent clinical data on the use of platinum-based
      chemotherapies for the treatment of these gastrointestinal cancers.

PMID- 15726530
TI  - Recent updates in the clinical use of platinum compounds for the treatment of
      gynecologic cancers.
AB  - Platinum compounds have long played a role in the treatment of gynecologic
      cancers. Single-agent cisplatin and carboplatin have shown activity in
      endometrial cancer, and more recent studies have begun to investigate a variety
      of new platinum-based combinations. In cervical cancer, chemotherapy is used
      primarily to treat advanced or recurrent disease. Agents with proven single-agent
      activity in this setting include cisplatin, ifosfamide, and doxorubicin, and a
      number of cisplatin-based combination therapies are under clinical investigation.
      A variety of cisplatin-based combinations have also been used in ovarian cancer
      chemotherapy, with more recent studies investigating the substitution of
      carboplatin or oxaliplatin for cisplatin and the addition of paclitaxel. This
      review will examine recent clinical data on the use of platinum-based
      chemotherapies for the treatment of these gynecologic cancers.

PMID- 15726531
TI  - Recent updates in the clinical use of platinum compounds for the treatment of
      lung, breast, and genitourinary tumors and myeloma.
AB  - Platinum compounds have shown activity in a broad spectrum of human tumors in
      vitro and in vivo. The clinical utility of platinum agents in gynecologic and
      gastrointestinal cancers (particularly oxaliplatin in colorectal cancer) has been
      well documented and platinum agents continue to be evaluated in a variety of
      other cancers. Given preclinical evidence of synergy among some platinum
      compounds and new anticancer agents, clinical trials exploring platinum-based
      combination therapies may yield improved treatment for a variety of malignancies.
      Recent clinical data on new chemotherapeutic strategies for the treatment of
      lung, breast, and genitourinary cancers and myeloma will be presented in this
      review.

PMID- 15726532
TI  - Dose and schedule as determinants of outcomes in chemotherapy for breast cancer.
AB  - Many cytotoxic agents for the adjuvant treatment of breast cancer are available,
      but they have produced only modest results, even when the tumor burden is low.
      This relative lack of efficacy may be attributed, in part, to the nonspecificity
      of the current regimens. Additionally, there is evidence that the chemotherapy
      doses used in clinical practice are not optimal, which potentially compromises
      the outcomes when the thresholds of dose intensity are not reached. Variations in
      treatment underscore the need to return to the basics of chemotherapy
      administration: dose, schedule, concentration threshold, and therapeutic index.
      In patients with metastatic breast cancer a clear dose-response curve has been
      shown with some agents, including anthracyclines. The E-max model, which in its
      simplest form assumes a direct relation between the dose of a drug and its
      effect, may be used to improve dosing in the adjuvant treatment of breast cancer.
      Consistent with this model, threshold effects have been observed in treatment
      with both anthracyclines and paclitaxel for breast cancer. There is also evidence
      that using dose-dense schedules may produce better outcomes with some regimens.
      Maintaining chemotherapy agents at full dose on schedule is crucial to treatment
      success, especially in adjuvant therapy. Consequently, treatment practices should
      use both dose intensity and dose compression to increase the likelihood of
      positive outcomes in patients with breast cancer.

PMID- 15726533
TI  - New treatment strategies for aggressive lymphoma.
AB  - For the past three decades chemotherapy with CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone) has been the standard
      treatment for aggressive non-Hodgkin's lymphoma (NHL), with only minor changes
      having been made to the regimen to increase its efficacy. Recently, however,
      clinical trials have shown significant improvements in outcome in aggressive NHL
      by showing the benefit of using dose-dense or accelerated schedules as well as by
      adding rituximab to the standard CHOP regimen. Maintaining the relative dose
      intensity (that is, delivering the full dose of the chemotherapy on schedule) is
      an important principle in achieving optimal outcomes in the treatment of NHL.
      Clinical studies have shown that dose reductions and delays result in poorer
      outcomes in patients with NHL, and in many cases greater dose intensity appears
      to result in greater overall and progression-free survival. In particular,
      compressing the delivery of the standard 21-day CHOP doses into a dose-dense 14
      day schedule has been shown to increase event-free survival, overall survival, or
      both in patients with diffuse large B-cell lymphoma. Consequently, the CHOP-14
      regimen (in which the dose intensity is 50% greater than that of the standard
      regimen) has been adopted by many oncologists for the treatment of aggressive
      NHL.

PMID- 15726535
TI  - Relevance of chemotherapy dose and schedule to outcomes in ovarian cancer.
AB  - The current standard of care in ovarian cancer is complete surgical cytoreduction
      followed by adjuvant (postoperative) platinum-based chemotherapy. Taxanes are
      frequently combined with platinum compounds in the adjuvant chemotherapy setting
      and, whether they are given in combination or sequentially, they produce greater
      progression-free and overall survival than historical combination regimens.
      Because the treatment of ovarian cancer relies on chemotherapy, this article
      reviews the evidence for a correlation between chemotherapy delivered at full
      dose on schedule (FDOS) and patient outcomes. Meta-analyses have suggested that
      the dose intensities of cisplatin and carboplatin correlate with survival.
      However, the findings in these hypothesis-generating analyses have not been
      confirmed in prospective trials. In addition, increasing the dose of cisplatin
      above a certain threshold is not recommended in ovarian cancer because of the
      greater toxicity with higher doses of platinum compounds. The delivered dose
      intensities of taxanes used as single agents have not been shown to correlate
      with patient outcomes, but adding a taxane to platinum compounds appears both to
      attenuate the toxicity of the platinum compounds and to facilitate the delivery
      of FDOS chemotherapy. In the literature on ovarian cancer there is no clear
      consensus on the benefit of maintaining FDOS chemotherapy. Clinical studies,
      especially a proposed trial of a dose-dense carboplatin and paclitaxel
      combination, may provide stronger evidence for the effect of FDOS chemotherapy in
      ovarian cancer.

PMID- 15726534
TI  - Perspectives in the treatment of colorectal cancer.
AB  - The availability of new chemotherapy agents in the last several years has had a
      significant impact on the treatment of colorectal cancer (CRC), but questions
      about how best to use these agents remain. In this article we review the evidence
      for maintaining full dose on schedule (FDOS) chemotherapy in CRC. To date,
      clinical studies have focused on determining which agents or combinations are
      optimal in advanced disease or the adjuvant setting. Combinations of irinotecan
      or oxaliplatin with 5-fluorouracil and leucovorin are currently being evaluated
      in the adjuvant treatment of CRC, and the addition of targeted biologic agents to
      standard chemotherapy regimens is being evaluated in the treatment of advanced
      disease. Few studies have investigated dose intensity in the adjuvant setting,
      and consequently, there is little evidence for a link between FDOS chemotherapy
      and outcomes. Nonetheless, the benefits of maintaining FDOS chemotherapy, as
      shown in trials in breast cancer and non-Hodgkin's lymphoma, may also hold true
      in CRC. Furthermore, several studies in metastatic CRC have found that greater
      survival can be achieved with dose-intensified chemotherapy. If FDOS chemotherapy
      is to become accepted in the treatment of CRC, end points other than overall
      survival may have to be assessed in metastatic disease and the concept will have
      to be investigated in the adjuvant setting. For now, the role of FDOS
      chemotherapy in CRC has not been adequately evaluated.

PMID- 15726536
TI  - The importance of chemotherapy dose intensity in lung cancer.
AB  - The evidence for the importance of maintaining full dose on schedule chemotherapy
      for lung cancer varies considerably by histologic type. Several studies have
      evaluated chemotherapy dose and dose intensity in small cell lung cancer; fewer
      studies have evaluated the importance of chemotherapy in non-small cell lung
      cancer. The current guidelines of the National Comprehensive Cancer Network
      recommend adjuvant chemotherapy in most patients with resectable disease, and
      there is increasing evidence that chemotherapy benefits elderly patients as much
      as younger patients. Clinical trials in the setting of palliative treatment of
      advanced non-small cell lung cancer have focused on testing new regimens rather
      than evaluating the impact of maintaining the dose and schedule of standard
      chemotherapy regimens. However, in light of the potential curative role of
      chemotherapy in the adjuvant setting, the optimal doses and schedules of these
      regimens may have an important impact on outcomes. In addition, data suggest that
      responses in the neoadjuvant setting correlate with survival, and this may also
      be an appropriate setting in which to test the effect of the chemotherapy dose
      and schedule. Survival is the primary measure of treatment efficacy, but other
      end points, such as quality of life and disease stability, should also be
      considered in advanced disease. Because new regimens will shape the choice of
      treatment in the adjuvant and neoadjuvant settings, it is important to determine
      the significance of maintaining full dose on schedule with conventional
      chemotherapy regimens to ensure optimal outcomes in the treatment of lung cancer.

PMID- 15726537
TI  - Corticobasal syndrome with novel argyrophilic glial inclusions.
AB  - A 42-year-old, left-handed woman first noted impaired dexterity of the dominant
      hand, soon followed by dysarthria and cognitive decline. Over a 4-year period,
      she developed severe left-sided apraxia with eventual neglect of the left arm and
      progressive extrapyramidal signs. Cognitive testing showed progressive executive,
      visuospatial, fluency, and naming impairment with relative preservation of
      memory. Single-photon emission computed tomography demonstrated asymmetric right
      posterior frontal and superior parietal hypoperfusion. The clinical impression
      was corticobasal degeneration. At autopsy, severe atrophy was seen in the
      perirolandic and frontal regions. There was marked neuronal loss and gliosis in
      the posterior frontal and precentral regions and less severe pathology in
      prefrontal, temporal, and parietal areas. Mild to moderate gliosis and neuronal
      loss were also seen in the putamen, globus pallidus, subthalamic, and dentate
      nuclei. Gallyas silver stain revealed numerous inclusions adjacent to
      oligodendrocyte nuclei in white and gray matter of affected cortical and
      subcortical regions. The gracile inclusions were wavy, slender, and stained
      positively with antibodies to ubiquitin and alphaB-crystallin but not to
      microtubule-associated proteins (tau, MAP1B, MAP2), tubulin, neurofilaments,
      glial fibrillary acidic protein, or alpha-synuclein. The argyrophilic inclusions
      identified in this case are distinct from those previously described in
      neurodegenerative diseases.

PMID- 15726538
TI  - More on the need for boosters 15 years after neonatal vaccination.

PMID- 15726539
TI  - Driving in Parkinson's disease: mobility, accidents, and sudden onset of sleep at
      the wheel.
AB  - Only few studies have addressed driving ability in Parkinson's disease (PD) to
      date. However, studies investigating accident proneness of PD patients are
      urgently needed in the light of motor disability in PD and--particularly--the
      report of "sleep attacks" at the wheel. We sent a questionnaire about sudden
      onset of sleep (SOS) and driving behavior to 12,000 PD patients. Subsequently, of
      6,620 complete data sets, 361 patients were interviewed by phone. A total of 82%
      of those 6,620 patients held a driving license, and 60% of them still
      participated in traffic. Of the patients holding a driving license, 15% had been
      involved in and 11% had caused at least one accident during the past 5 years. The
      risk of causing accidents was significantly increased for patients who felt
      moderately impaired by PD, had an increased Epworth Sleepiness Scale (ESS) score,
      and had experienced SOS while driving. Sleep attacks at the wheel usually
      occurred in easy driving situations and resulted in typical fatigue-related
      accidents. Those having retired from driving had a more advanced (subjective)
      disease severity, higher age, more frequently female gender, an increased ESS
      score, and a longer disease duration. The study revealed SOS and daytime
      sleepiness as critical factors for traffic safety in addition to motor
      disabilities of PD patients. The results suggest that real sleep attacks without
      any prior sleepiness are rare. However, our data underline the importance of
      mobility for patients and the need for further studies addressing the ability to
      drive in PD.

PMID- 15726540
TI  - Long-term efficacy and safety of pramipexole in advanced Parkinson's disease:
      results from a European multicenter trial.
AB  - A double-blind, placebo-controlled study with a subsequent open-label phase was
      conducted in 354 patients with Parkinson's disease (PD) and motor fluctuations
      under individually adjusted therapy with levodopa. During the double-blind phase
      174 patients received pramipexole and 180 placebo. In agreement with previous
      studies, pramipexole treatment improved UPDRS sum scores of parts II and III by
      30% and off times by approximately 2.5 hours per day. Differences between the
      treatment groups became significant at a daily dose of 0.75 mg of pramipexole
      dihydrochloride. We, furthermore, performed post hoc analyses with respect to
      resting tremor and depression. Patients with pronounced resting tremor derived a
      clear benefit from pramipexole treatment compared with placebo. In addition,
      pramipexole significantly improved the subitems motivation/initiative and
      depression in a subpopulation with increased Unified Parkinson's Disease Rating
      Scale I scores at the time of inclusion. There were 262 patients who were
      subsequently enrolled into the open-label study featuring a maximum duration of
      up to 57 months. Statistical analysis revealed good long-term efficacy and
      tolerability of pramipexole. Overall, only a low prevalence of somnolence was
      found. In summary, this study provides additional level I evidence of the
      usefulness of pramipexole, suggests a particular tremorlytic and a possible
      antidepressant action of this compound, and addresses for the first time its
      efficacy and safety during long-term administration in advanced PD.

PMID- 15726542
TI  - Phase II study of hepatic intraarterial epirubicin and cisplatin, with systemic 5
      fluorouracil in patients with unresectable biliary tract tumors.
AB  - BACKGROUND: Patients with unresectable biliary tract carcinomas have a very poor
      prognosis. To improve the efficacy and tolerance of the ECF regimen (epirubicin
      at a dose of 50 mg/m2, cisplatin at a dose of 60 mg/m2, and 5-fluorouracil [5-FU]
      at a dose of 200 mg/m2 per day by continuous infusion), the authors designed a
      novel approach that combined locoregional and systemic chemotherapy with the same
      agents at the same dosages. METHODS: Thirty consecutive patients with advanced or
      metastatic biliary tumors were treated with epirubicin at a dose of 50 mg/m2 and
      cisplatin at a dose of 60 mg/m2 administered as a bolus in the hepatic artery on
      Day 1, combined with systemic continuous infusion of 5-FU at a dose of 200 mg/m2
      per day, from Day 1 to Day 14, every 3 weeks. RESULTS: Tumor sites were the
      intrahepatic bile ducts in 25 patients and the gallbladder in 5 patients. The
      overall response rate was 40% (12 of 30 patients), including 1 complete response
      and 11 partial responses. Stable disease was observed in 12 of 30 patients (40%)
      and progressive disease in 6 of 30 patients (20%). The median progression-free
      and overall survival periods were 7.1 and 13.2 months, respectively, and the 1
      year and 2-year survival rates were 54% and 20%, respectively. Performance status
      improved in 9 of 30 patients (30%) and a weight gain of > 7% was observed in 4 of
      30 patients (13%). The treatment was well tolerated with minimal hematologic
      toxicity. The major clinical problem was the deep venous thrombosis related to
      the central venous catheter, which occurred in 5 patients (17%). CONCLUSIONS:
      This novel combined locoregional and systemic chemotherapeutic regimen was found
      to be active and safe for patients with advanced biliary tract carcinoma.

PMID- 15726541
TI  - Acute phase HBV-specific T cell responses associated with HBV persistence after
      HBV/HCV coinfection.
AB  - To characterize acute-phase hepatitis B virus (HBV)-specific T cell responses
      associated with self-limited and persistent HBV infections, we compared a patient
      with acute HBV/HCV coinfection, who was able to control HCV but developed chronic
      hepatitis B, with patients who resolved acute HBV infection spontaneously. Acute
      phase CD4 responses were efficient in self-limited infections but undetectable in
      the coinfected patient with HBV persistence. CD8 responses were multispecific
      irrespective of the outcome of infection, but the CD8 repertoire associated with
      HBV persistence lacked the most dominant specificities detectable in self-limited
      infections. In conclusion, insufficient CD4 help and defective CD8 repertoire may
      play a role at the early stages of infection in influencing HBV persistence.

PMID- 15726543
TI  - Clinicopathologic and protein expression differences between cardia carcinoma and
      noncardia carcinoma of the stomach.
AB  - BACKGROUND: Although the incidence of adenocarcinoma of the stomach has decreased
      over the past several decades, gastric cardia carcinoma has increased over the
      same period. METHODS: The clinicopathologic characteristics and
      immunohistochemical staining results of 21 proteins were investigated in 165
      patients with cardia carcinoma, including 74 patients with true cardia carcinoma
      and 91 patients with subcardia carcinoma, and the results were compared with the
      results from 564 patients with noncardia carcinoma. RESULTS: In the
      clinicopathologic analysis, patients who had cardia carcinoma tended to have
      tumors with poorly differentiated histology according to the World Health
      Organization classification system (P = 0.012), diffuse type according to the
      Lauren classification system (P = 0.049), and advanced pathologic TNM stage (P <
      0.001). On immunohistochemical staining, loss of the p16 (P = 0.038) and smad4 (P
      < 0.001) tumor suppressor genes was more frequent in cardia carcinoma than in
      noncardia carcinoma. Carcinoembryonic antigen and CD44 overexpression were more
      frequent in patients with cardia carcinoma (P < 0.05). Conversely, patients who
      had cardia carcinoma exhibited less frequent expression of MUC1 (P = 0.008) and
      MUC5AC (P = 0.006) compared with patients who had noncardia carcinoma. Epstein
      Barr virus infection was more common in patients with cardia carcinoma (P <
      0.001). In the survival analysis, the patients with cardia carcinoma had a poorer
      prognosis. In the multivariate analysis, tumor location in the cardia was
      confirmed as an independent, poor prognostic factor in patients with gastric
      carcinoma. CONCLUSION: Cardia carcinoma and noncardia carcinoma differed in their
      clinicopathologic characteristics and in their alterations of gene expression, as
      evaluated by immunohistochemistry. The current results support the hypothesis
      that cardia carcinoma forms a specific category of gastric carcinoma that is
      distinct from noncardia carcinoma.

PMID- 15726544
TI  - Screening for psychologic distress in ambulatory cancer patients.
AB  - BACKGROUND: Based on evidence that psychologic distress often goes unrecognized
      although it is common among cancer patients, clinical practice guidelines
      recommend routine screening for distress. For this study, the authors sought to
      determine whether the single-item Distress Thermometer (DT) compared favorably
      with longer measures currently used to screen for distress. METHODS: Patients (n
      = 380) who were recruited from 5 sites completed the DT and identified the
      presence or absence of 34 problems using a standardized list. Participants also
      completed the 14-item Hospital Anxiety and Depression Scale (HADS) and an 18-item
      version of the Brief Symptom Inventory (BSI-18), both of which have established
      cutoff scores for identifying clinically significant distress. RESULTS: Receiver
      operating characteristic (ROC) curve analyses of DT scores yielded area under the
      curve estimates relative to the HADS cutoff score (0.80) and the BSI-18 cutoff
      scores (0.78) indicative of good overall accuracy. ROC analyses also showed that
      a DT cutoff score of 4 had optimal sensitivity and specificity relative to both
      the HADS and BSI-18 cutoff scores. Additional analyses indicated that, compared
      with patients who had DT scores < 4, patients who had DT scores > or = 4 were
      more likely to be women, have a poorer performance status, and report practical,
      family, emotional, and physical problems (P < or = 0.05). CONCLUSIONS: Findings
      confirm that the single-item DT compares favorably with longer measures used to
      screen for distress. A DT cutoff score of 4 yielded optimal sensitivity and
      specificity in a general cancer population relative to established cutoff scores
      on longer measures. The use of this cutoff score identified patients with a range
      of problems that were likely to reflect psychologic distress.

PMID- 15726545
TI  - Racial differences in exposure and glucuronidation of the tobacco-specific
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
AB  - BACKGROUND: In the United States, Blacks who smoke cigarettes have a higher mean
      blood concentration of the nicotine metabolite cotinine than White smokers. It
      has not been determined whether there are racial differences in the exposure to
      the cigarette smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) and in the detoxification of NNK metabolites. METHODS: A community-based
      cross-sectional survey of 69 Black and 93 White smokers was conducted in lower
      Westchester County, New York. Information on smoking and lifestyle habits was
      collected and urinary concentrations of several tobacco smoke biomarkers were
      compared, including the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL) and its glucuronide (NNAL-Gluc). A frequency histogram and probit
      plot of NNAL-Gluc:NNAL ratios were constructed to determine slow and rapid
      glucuronidation phenotypes. RESULTS: The mean concentrations of total NNAL,
      urinary cotinine, plasma cotinine, and thiocyanate were significantly higher in
      Black men than in White men for each cigarette smoked. In women, the only
      biomarker that was significantly elevated in Blacks was plasma cotinine. A higher
      proportion of White versus Black women was categorized as "rapid" glucuronidators
      (two-tailed exact test, P = 0.03). In men, there were no significant differences
      in NNAL-Gluc:NNAL phenotypes. CONCLUSIONS: The higher rates of lung carcinoma in
      black men may be due in part to a higher level of exposure to tobacco smoke
      carcinogens.

PMID- 15726546
TI  - Interobserver agreement in the interpretation of anal intraepithelial neoplasia.
AB  - BACKGROUND: Anal carcinoma incidence is increasing, and is highest among men with
      human immunodeficiency virus (HIV) infection who have sex with men. Anal
      carcinoma and anal intraepithelial neoplasia (AIN) are ascertained on tissue
      histology, but requires invasive procedures. Screening for AIN using anal
      cytology was suggested. The authors evaluated agreement on cytologic and biopsy
      specimens from HIV-positive men undergoing anal carcinoma screening. METHODS: One
      hundred twenty-nine HIV-positive men with a history of anal-receptive intercourse
      underwent anal cytology, anoscopy, and biopsy. Four pathologists independently
      assessed cytology and biopsy specimens and reached consensus for discordant
      cases. RESULTS: Each pathologist evaluated 120 cytology and 155 biopsy specimens.
      The weighted kappa value for overall agreement was 0.54 (95% confidence interval
      [CI], 0.49-0.59) for cytology specimens and 0.59 (95%CI, 0.55-0.63) for biopsy
      specimens. The median kappa values for pairwise agreement among pathologists and
      for agreement with consensus were, respectively, 0.69 and 0.77 for cytology and
      0.66 and 0.75 for biopsy. At least 3 pathologists were in agreement for 92
      (76.7%) cytology and 134 (86.5%) biopsy specimens. Reliability for the Bethesda
      classification system was at least moderate, except for the cytologic category of
      atypical squamous cells of undetermined significance (kappa = 0.12). Fourteen of
      29 (48.3%) cytology specimens and 36 of 47 (76.6%) biopsy specimens with
      consensus interpretation of high-grade squamous intraepithelial lesions (HSIL)
      were interpreted originally as HSIL by > or = 3 pathologists. The kappa value for
      agreement with consensus distinguishing HSIL from non-HSIL ranged from 0.55 to
      0.88 for cytology specimens and from 0.76 to 0.94 for biopsy specimens.
      CONCLUSIONS: Agreement for cytologic and biopsy interpretations was generally at
      least moderate. Nevertheless, these results supported the need for disease
      indicators with greater reliability.

PMID- 15726548
TI  - The clinical significance of malignant pleural effusions in patients with
      optimally debulked ovarian carcinoma.
AB  - BACKGROUND: The objective of this study was to determine the impact of malignant
      pleural effusions on survival in patients with optimally debulked, advanced
      epithelial ovarian carcinoma. METHODS: The authors conducted a retrospective
      review of all patients with advanced epithelial ovarian carcinoma who underwent
      optimal primary cytoreduction at their institution between January 1987 and
      August 2000. Survival rates were compared between patients with optimally
      debulked Stage IIIC epithelial ovarian carcinoma and patients with optimally
      debulked Stage IV epithelial ovarian carcinoma (according to the International
      Federation of Gynecology and Obstetrics [FIGO] staging system) based on cytology
      proven malignant pleural effusions. RESULTS: Ninety-nine patients were
      identified, and 97 of those patients were evaluable. The group with Stage IIIC
      disease included 76 patients, and the group with Stage IV disease included 21
      patients. The median age at diagnosis was 55 years (range, 26-88 years). The
      majority of patients received platinum-based chemotherapy after undergoing
      optimal primary cytoreduction. Age, tumor grade and histology, and the percentage
      of patients with ascites were similar in the two groups. The median survival rate
      was 58 months for patients who had Stage IIIC disease and 30 months for patients
      who had Stage IV disease (P = 0.016). CONCLUSIONS: Although both groups underwent
      optimal cytoreduction in the abdomen/pelvis and were treated in a similar
      fashion, the median survival rate of patients with malignant pleural effusions
      was significantly shorter than the survival of patients without effusions. Many
      factors that led to or were manifested by pleural effusions, such as undetected
      bulky residual intrathoracic disease, may have been the cause for this survival
      difference. In the patients with effusions, one or more of these contributing
      factors may have led to the observed decreased survival rate, warranting further
      investigation.

PMID- 15726547
TI  - Lower and central tumor location correlates with lymphoscintigraphy drainage to
      the internal mammary lymph nodes in breast carcinoma.
AB  - BACKGROUND: Radiation to the internal mammary chain (IMC) may be indicated for
      breast carcinoma patients with positive axillary sentinel lymph nodes (SLNs) and
      lymphoscintigraphic evidence of drainage to the IMC. The purpose of this study
      was to identify predictors of IMC drainage in patients with positive axillary
      SLNs. METHODS: The records of 297 breast carcinoma patients with positive
      axillary SLNs and preoperative lymphoscintigraphy were reviewed between 1995 and
      2002. Radiolabeled colloid was injected peritumorally with lymphoscintigraphy
      performed 30-60 minutes later. Drainage to the regional nodes of 279 patients was
      seen on lymphoscintigraphy. Associations among patient and tumor-related factors
      and drainage to the IMC were examined. RESULTS: Drainage to the IMC on
      lymphoscintigraphy was seen in 63 patients (21%). IMC drainage only occurred in 4
      patients, and 59 patients had both axillary and IMC drainage. The only variable
      that correlated with IMC drainage was tumor location (P = 0.017). Rates of
      drainage to the IMC were 14.1% for upper outer quadrant (n = 128), 16.7% for
      upper inner quadrant (n = 30), 31.6% for lower outer quadrant (n = 19), 42.9% for
      lower inner quadrant (n = 14), and 28.4% for central tumors (n = 88). IMC
      drainage rates differed significantly between upper and lower tumors (lower 36.4%
      vs. central 28.4% vs. upper 14.6%, P = 0.003) but not between medial and lateral
      tumors (medial 25.0% vs. central 28.4% vs. lateral 16.3%, P = 0.077).
      CONCLUSIONS: Patients with tumors in the lower or central breast and positive
      axillary SLNs have increased incidence of drainage to the IMC. Preoperative
      lymphoscintigraphy can help to define the nodal basins at risk for harboring
      disease.

PMID- 15726549
TI  - Mass spectrometric detection of biotinylated peptides captured by avidin
      functional affinity electrophoresis.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was
      used to detect biotinylated peptides captured by avidin functional affinity
      electrophoresis (AFAEP). Peptide samples loaded onto AFAEP were heated with
      sodium dodecyl sulfate to ensure that the peptides are negatively charged, and
      thus migrate electrophoretically toward the cathode through the embedded avidin
      zone in the middle of the gel. To detect the biotinylated peptides, the band
      containing the avidin-biotinylated peptide complexes was excised from a 7.5% w/v
      native polyacrylamide gel, and biotinylated peptides were extracted with aqueous
      95% v/v formamide (pH 8.2), aqueous 6 M guanidine HCl (pH 1.5), or water, at
      temperatures from 4 to 95 degrees C for periods from 5 min to 24 h. It was
      observed that all three solvents are capable of extracting biotinylated peptides
      and avidin from the gel, but the best results were obtained with aqueous 95% v/v
      formamide (pH 8.2) at 65 degrees C for 20 min. However, some AFAEP-captured
      biotinylated peptides are not stable and are extensively modified by formamide
      during extraction at too high a temperature or too long an extraction time.

PMID- 15726550
TI  - A large simple clinical trial prototype for assessment of OTC drug effects using
      patient-reported data.
AB  - PURPOSE: Innovative methods are needed to assess risks related to treatment for
      common medical conditions, where therapy is usually patient-directed or over-the
      counter (OTC), and where tolerability, i.e. patient experienced events, may
      affect patterns of use. A large-scale, blinded, randomised trial was conducted to
      compare the tolerability of paracetamol (acetaminophen), aspirin and ibuprofen at
      OTC doses, with patient-reported adverse event (AE) data as the primary outcome.
      METHODS: Patients with mild to moderate pain were randomised to either:
      paracetamol up to 3 g/d, aspirin up to 3 g/d or ibuprofen up to 1200 mg/d for 7
      days. Patients recorded AE and severity in a diary as the primary data source.
      After inclusion, contact with patients by general practitioner (GP) investigators
      was by telephone after 24 hours and 7-9 days, and unscheduled visits, when GPs
      recorded AE. The study outcome was the frequency of significant adverse event
      (SGAE) (serious, severe, moderate or undefined intensity, or resulting in
      withdrawal or an investigator visit). RESULTS: Of 8677 patients included, 44
      patients were non-evaluable, leaving 8633 evaluable patients; 1347 patients
      reported SGAE (paracetamol: 14.5%, aspirin: 18.7%, ibuprofen: 13.7%). Completed
      diaries were returned by 98.5% of patients, and only 49 cases were lost to follow
      up (0.6%). Almost all patients were contacted by telephone, 99.3% at the first
      call, and 98.5% at the second. Most SGAE were reported by patients; only 27
      patients (2%) had a SGAE reported only by the GP. The tolerability rankings by
      treatment were consistent for all categories of SGAE: aspirin had the highest
      incidence of SGAE, and ibuprofen and paracetamol, lower, comparable incidences.
      CONCLUSIONS: A large, simple, randomised trial with patient-generated data can
      provide a sensitive source of information on AE, particularly in comparative
      safety assessments of OTC medications and other short-term therapies. This
      suggests reconsideration of the view that investigators are the most valid source
      for identifying and reporting AE.

PMID- 15726551
TI  - Water-induced rearrangement of a platinacyclic carbene produces a platinacyclic
      carbaphosphazene with an intraannular Pt--C bond in a Pt--N--P--N--P--C ring.

PMID- 15726552
TI  - Corundum, diamond, and PtS metal-organic frameworks with a difference: self
      assembly of a unique pair of 3-connecting D2d-symmetric 3,3',5,5'-tetrakis(4
      pyridyl)bimesityl.

PMID- 15726553
TI  - Stereoselective transformations of trihalomethylcarbinols induced by chromous
      chloride.

PMID- 15726554
TI  - Adsorption and self-assembly of peptides on mica substrates.

PMID- 15726555
TI  - Acid-initiated stereospecific polymerization of isocyanopeptides.

PMID- 15726556
TI  - Conformational control of photochromic reactivity in a diarylethene single
      crystal.

PMID- 15726557
TI  - Electrochromism of titanate-based nanotubes.

PMID- 15726558
TI  - Photoswitching of stereoselectivity in catalysis using a copper dithienylethene
      complex.

PMID- 15726559
TI  - Synthesis, reactivity, and structural characterization of a 14-vertex carborane.

PMID- 15726560
TI  - Highly porous, homochiral metal-organic frameworks: solvent-exchange-induced
      single-crystal to single-crystal transformations.

PMID- 15726561
TI  - Relay ring-closing metathesis-a strategy for achieving reactivity and selectivity
      in metathesis chemistry.

PMID- 15726562
TI  - Floating single hydrogen molecule in an open-cage fullerene.

PMID- 15726563
TI  - Molecular apple peels.

PMID- 15726564
TI  - Palladium-(N-heterocyclic carbene) hydrogenation catalysts.

PMID- 15726565
TI  - Influence of grain type on the insecticidal efficacy of two diatomaceous earth
      formulations against Rhyzopertha dominica (F) (Coleoptera: Bostrychidae).
AB  - Laboratory bioassays were carried out in order to evaluate the effectiveness of
      two diatomaceous earth (DE) formulations, Insecto and SilicoSec, against adults
      of Rhyzopertha dominica (F) in eight different grain commodities. The adherence
      of the two DEs to each grain was also measured. The eight grains tested were
      wheat, whole barley, peeled barley, oats, rye, triticale, rice and maize. These
      commodities were treated with the DEs at three rates, 0.75, 1.0 and 1.5 g DE kg(
      1) grain. The mortality of R dominica adults was measured after 24 h, 48 h, 7
      days and 14 days of exposure in the treated grains at 26 degrees C and 55% RH.
      After the 14-day mortality count, all adults were removed and the treated grains
      retained under the same conditions for a further 60 days. The treated grains were
      subsequently examined for F1 progeny. Significant differences were recorded among
      the eight grain types as well as between the DE formulations tested. After 14
      days of exposure, even at the lowest DE rate for both formulations, adult
      mortality was high (>90%) in wheat and triticale. In contrast, adult mortality
      was significantly lower in peeled barley. Increasing the rate improved the
      efficacy of the DEs significantly in only some of the grains tested. Reproductive
      capacity in all the treated grains was significantly suppressed when compared
      with untreated grains. Generally, more F1 individuals of R dominica were noted in
      the treated peeled barley than in the other commodities. Significant differences
      in the percentage of DE retention were noted among the eight grains. The highest
      retention level was noted in rice (>87%) and the lowest in maize (<6%). However,
      the degree of DE adherence to a given grain was not always indicative of the
      effectiveness of DE against R dominica.

PMID- 15726566
TI  - Techniques and parameters used in compatibility tests between Beauveria bassiana
      (Bals) Vuill and in vitro phytosanitary products.
AB  - The objective of this work was to test and compare different techniques used in
      tests for compatibility between the entomopathogenic fungus Beauveria bassiana
      (Balsamo) Vuill and phytosanitary products, in order to develop a protocol for in
      vitro tests. Four modes of contact were studied between B bassiana (CG432) and
      the fungicides iprodione (Rovral) 500 g litre(-1) SC) and azoxystrobin (Amistar)
      500 g kg(-1) WG), and the insecticide endosulfan (Thiodan) 350 g litre(-1) EC),
      at three rates. The techniques consisted in incorporating the products into the
      culture medium (IM), combining the conidia into the products mix (MP) and
      spraying the products before (SB) and after (SA) inoculation of the fungus on
      Petri dishes. The fungitoxic effect of the products was studied on the basis of
      parameters such as germination, colony-forming units (CFUs), vegetative growth
      and sporulation. The effect of azoxystrobin on conidial germination was
      significantly higher in the IM technique than in the other techniques. With
      regard to CFUs, the IM and SB techniques showed the greatest differences relative
      to the control. Vegetative growth and sporulation were more affected when
      azoxystrobin was sprayed before the fungus was applied. At the commercial rate,
      iprodione had a greater effect on the CFU parameter in the IM and MP techniques,
      and on vegetative growth in the IM technique, than the other techniques used;
      however, there was no significant difference occurred between the techniques at
      the commercial rate with respect to germination and sporulation. Endosulfan was
      more toxic to germination in techniques SB and SA, and to the CFUs parameter in
      techniques IM and MP. As to vegetative growth and sporulation, regardless of
      rate, a more pronounced effect was observed in IM than in the other techniques.
      It can be inferred that there are differences between techniques and that a
      standardization of the compatibility tests is necessary. Another inference is
      that these techniques should reflect realistic exposure of the fungus to chemical
      formulations under field conditions.

PMID- 15726567
TI  - The carboxyterminal processing protease of D1 protein: expression, purification
      and enzymology of the recombinant and native spinach proteins.
AB  - The carboxyterminal processing protease of D1 protein (CtpA) is predicted to be
      an excellent target for a general broad-spectrum herbicide. The gene for spinach
      CtpA has been expressed in Escherichia coli. The expressed protein that was found
      mainly in inclusion bodies has been purified and refolded on a nickel-chelate
      column. Active recombinant CtpA was recovered. Two assays for CtpA activity were
      developed, a medium-throughput HPLC assay using a fluorescent substrate and a
      high-throughput assay based on fluorescence polarization capable of application
      in a high-throughput 96-well plate format. This high-throughput assay was
      developed to screen chemistry for CtpA inhibitors. Native spinach CtpA was
      partially purified and the native and recombinant enzymes were compared
      kinetically for their K(m) and V(max) values using different peptide substrates.
      Native CtpA partially purified from spinach was shown to have similar kinetic
      properties to recombinant CtpA. Antibodies developed against the recombinant
      protein were used to estimate the in planta abundance of the native enzyme in
      spinach. Since only a small proportion of the recombinant protein is refolded
      during isolation and it appears that only a small proportion of this enzyme is
      active, size-exclusion chromatography and light scattering experiments were
      performed on rCtpA in order to gain insight into its structure and the reasons
      why most of the protein is not active. The use of rCtpA to screen for herbicidal
      compounds and the more general question of how good a herbicide target the enzyme
      is are discussed.

PMID- 15726568
TI  - The behavior of transition metal nitrido bonds towards protonation rationalized
      by means of localized bonding schemes and their weights.
AB  - A new computational scheme is applied to rationalize the different protonation
      behaviors of the nitrido complexes [L'Mn(V)(N)(acac)](+), [LCr(V)(N)(acac)](+),
      and [LV(V)(N)(acac)](+). L and L' represent the macrocycles 1,4,7
      triazacyclononane and its N-methylated derivative, respectively, and acac is the
      bidentate monoanion pentane-2,4-dionate. The bonds of the complexes are
      partitioned into bonds to be investigated and bonds of lesser interest. The
      investigated bonds are the transition metal nitrido bonds M(V)[triple chemical
      bond]N| (M = Mn, Cr, and V) and the bonds of lesser interest are located in the
      ligands. The ligand bonds are described by means of the strongly occupied natural
      bond orbitals. The electrons in the M(V)[triple chemical bond]N| nitrido bonds,
      however, are treated more accurately. A full configuration interaction procedure
      is applied in the space spanned by the strongly occupied natural bond orbitals
      and their corresponding antibonding orbitals. Localized bonding schemes and their
      weights are obtained for the d(pi)-p(pi) bonds of interest. This is achieved by
      representing the two-center natural bond orbitals for a d(pi)-p(pi) bond by the
      one-center natural hybrid orbitals localized at the bond atoms. The obtained
      bonding schemes are close to orthogonal valence bond structures. Their weights
      indicate that the nitrido nitrogen in [LV(V)(N)(acac)](+) is more easily
      protonated than the nitrido nitrogens in [L'Mn(V)(N)(acac)](+) and
      [LCr(V)(N)(acac)](+). This result is in good accord with experiment.

PMID- 15726570
TI  - Electronic structure study of the initiation routes of the dimethyl sulfide
      oxidation by OH.
AB  - In the present work the potential energy surface (PES) corresponding to the
      different initiation routes of the oxidation mechanism of DMS by hydroxyl radical
      in the absence of O(2) has been studied, and connections among the different
      stationary points have been established. Single-point high level electronic
      structure calculations at lower level optimized geometries have been shown to be
      necessary to assure convergence of energy barriers and reaction energies. Our
      results demonstrate that the oxidation of DMS by OH turns out to be initiated via
      three channels: a hydrogen abstraction channel that through a saddle point
      structure finally leads to CH(3)SCH(2) + H(2)O, an addition-elimination channel
      that firstly leads to an adduct complex (AD) and then via an elimination saddle
      point structure finally gives CH(3)SOH and CH(3) products, and a third channel
      that through a concerted pathway leads to CH(3)OH and CH(3)S. The H-abstraction
      and the addition-elimination channels initiate by a common pathway that goes
      through the same reactant complex (RC). Our theoretical results agree quite well
      with the branching ratios experimentally assigned to the formation of the
      different products. Finally, the calculated equilibrium constants of the
      formation of the complex AD and the hexadeuterated complex AD from the
      corresponding reactants, as a function of the temperature, are in good accordance
      with the experimental values.

PMID- 15726569
TI  - Computational methods for the study of enzymic reaction mechanisms III: a
      perturbation plus QM/MM approach for calculating relative free energies of
      protonation.
AB  - We describe a coupling parameter, that is, perturbation, approach to effectively
      create and annihilate atoms in the quantum mechanical Hamiltonian within the
      closed shell restricted Hartree-Fock formalism. This perturbed quantum mechanical
      atom (PQA) method is combined with molecular mechanics (MM) methods (PQA/MM)
      within a molecular dynamics simulation, to model the protein environment (MM
      region) effects that also make a contribution to the overall free energy change.
      Using the semiempirical PM3 method to model the QM region, the application of
      this PQA/MM method is illustrated by calculation of the relative protonation free
      energy of the conserved OD2 (Asp27) and the N5 (dihydrofolate) proton acceptor
      sites in the active site of Escherichia coli dihydrofolate reductase (DHFR) with
      the bound nicotinamide adenine dinucleotide phosphate (NADPH) cofactor. For a
      number of choices for the QM region, the relative protonation free energy was
      calculated as the sum of contributions from the QM region and the interaction
      between the QM and MM regions via the thermodynamic integration (TI) method. The
      results demonstrate the importance of including the whole substrate molecule in
      the QM region, and the overall protein (MM) environment in determining the
      relative stabilities of protonation sites in the enzyme active site. The PQA/MM
      free energies obtained by TI were also compared with those estimated by a less
      computationally demanding nonperturbative method based on the linear response
      approximation (LRA). For some choices of QM region, the total free energies
      calculated using the LRA method were in very close agreement with the PQA/MM
      values. However, the QM and QM/MM component free energies were found to differ
      significantly between the two methods.

PMID- 15726571
TI  - Fitting complex potential energy surfaces to simple model potentials: application
      of the simplex-annealing method.
AB  - A stochastic method of optimization, which combines simulated annealing with
      simplex, is implemented to fit the parameters of a simple model potential. The
      main characteristic of the method is that it explores the whole space of the
      parameters of the model potential, and therefore it is very efficient in locating
      the global minimum of the cost function, in addition to being independent of the
      initial guess of the parameters. The method is employed to fit the complex
      intermolecular potential energy surface of the dimer of water, using as a
      reference the spectroscopic quality anisotropic site-site potential of Feller et
      al. The simple model potential chosen for its reparameterization is the MCY model
      potential of Clementi et al. The quality of the fit is assessed by comparing the
      geometry of the minimum, the harmonic frequencies, and the second virial
      coefficients of the parameterized potential with the reference one. Finally, to
      prove more rigorously the robustness of this method, it is compared with standard
      nonstochastic methods of optimization.

PMID- 15726572
TI  - Double proton transfer and one-electron oxidation behavior in double H-bonded
      glycinamide-glycine complex in the gas phase.
AB  - The behaviors of double proton transfer (DPT) occurring in a representative
      glycinamide-glycine complex have been investigated employing the B3LYP/6-311++G**
      level of theory. Thermodynamic and especially kinetic parameters, such as
      tautomerization energy, equilibrium constant, and barrier heights have been
      discussed, respectively. The relevant quantities involved in the DPT process
      including geometrical changes, interaction energies, and deformation energies
      have also been studied. Analogous to that of tautomeric process assisted with a
      formic acid molecule, the participation of a glycine molecule favors the
      proceeding of the proton transfer (PT) for glycinamide compared with that without
      mediator-assisted case. The DPT process proceeds with a concerted mechanism
      rather than a stepwise one because no zwitterionic complexes have been located
      during the DPT process. The barrier heights are 12.14 and 0.83 kcal/mol for the
      forward and reverse directions, respectively. However, both of them have been
      reduced by 3.10 and 2.66 kcal/mol to 9.04 and -1.83 kcal/mol with further
      inclusion of zero-point vibrational energy (ZPVE) corrections, where the
      disappearance of the reverse barrier height implies that the reverse reaction
      should proceed with barrierless spontaneously, analogous to those of DPTs
      occurring between glycinamide and formic acid (or formamide). Additionally, the
      oxidation process for the double H-bonded glycinamide-glycine complex has also
      been investigated. The oxidated product is characterized by a distonic radical
      cation due to the fact that one-electron oxidation takes place on glycine
      fragment and a proton has been transferred from glycine to glycinamide fragment
      spontaneously. As a result, the vertical and adiabatic ionization potentials for
      the neutral complex have been determined to be about 8.71 and 7.85 eV,
      respectively, where both of them have been reduced by about 0.54 (1.11) and 0.75
      (1.13) eV relative to those of isolated glycinamide (glycine) due to the
      formation of the intermolecular H-bond.

PMID- 15726573
TI  - Cinosulfuron: chemical and biological degradability, adsorption and dissipation
      in flooded paddy field sediment.
AB  - Cinosulfuron is a sulfonylurea herbicide largely used in the extensive cultures
      of flooded rice in North Italy. The degradation of cinosulfuron has been
      investigated in sterile aqueous solutions at 30 degrees C at different pH values.
      It was rapidly degraded at acidic pH (half-lives 3, 9 and 43 days at pH 4, 5 and
      6, respectively) while the half-life was > 1 year at pH 7 and 9. Two degradation
      products formed by cleavage of the sulfonylurea bridge were identified by LC-MS.
      Degradation by selected mixed microbial cultures tested in aerobic and anaerobic
      conditions was very slow and attributable to chemical hydrolysis due to the
      acidic pH of the cultural broths. Degradation took place in freshly collected
      rice field water treated for two years with cinosulfuron but, in this case also,
      chemical hydrolysis prevailed over microbial degradation. In contrast, in flooded
      sediment simulating the paddy field environment, the dissipation rate of
      cinosulfuron was higher than expected from chemical hydrolysis according to the
      pH of the system, indicating the involvement of soil microflora. Although the
      herbicide exhibited a reduced affinity for the sediment surfaces demonstrated by
      the low value of the K(f) Freundlich coefficient (0.87 on a micromolar basis),
      the rapid dissipation observed in the simulated paddy field should prevent its
      leaching to ground water.

PMID- 15726574
TI  - Adult-onset neuronal ceroid lipofuscinosis type B in an African-American.
AB  - We describe a rare case of adult-onset neuronal ceroid lipofuscinosis (NCL) type
      B with probable autosomal dominant inheritance, exhibiting behavioral and
      cognitive abnormalities and extrapyramidal findings. Ultrastructural examination
      revealed abundant fingerprint profiles in several cell types. To our knowledge,
      this is the first reported case of an African-American with adult-onset NCL.

PMID- 15726576
TI  - Contributing geography.

PMID- 15726575
TI  - Nerve stimulation boosts botulinum toxin action in spasticity.
AB  - Spasticity leads to functional and structural changes in nerves and muscles,
      which alter skeletal muscle function. To evaluate whether short-term electrical
      nerve stimulation (NS) improves the effect of botulinum toxin in spastic skeletal
      muscle, we studied changes in the amplitude of the compound muscle action
      potential (CMAP) recorded from the extensor digitorum brevis (EDB) muscle in
      response to peroneal nerve stimulation at the ankle after injection of botulinum
      toxin type A (BTXA) alone or combined with short-term NS. In paraparetic
      patients, both EDB muscles were injected with BTXA; and NS was applied to one EDB
      muscle alone. All patients received a 30-minute session of electrical NS once a
      day for 5 consecutive days after BTXA injection. We used two different
      stimulation frequencies (low-frequency, 4 Hz; and high-frequency, 25 Hz). EDB
      CMAP amplitudes were evaluated before BTXA injection (day 0) and changes in CMAP
      amplitude, expressed as a percentage (CMAP%), were measured at various time
      points over a 30-day period after BTXA injection. We compared changes in the
      CMAP% amplitude on the stimulated and contralateral nonstimulated sides. We also
      studied the electromyographic activity recorded from EDB muscles over a 30-day
      period. CMAP% amplitudes measured at all time points after BTXA injections were
      significantly reduced in both EDB muscles. On days 4, 10, and 15, the CMAP%
      amplitude reduction was significantly greater for the low-frequency stimulated
      EDB than for the contralateral nonstimulated EDB. No significant differences in
      CMAP% were observed for the high-frequency stimulated and nonstimulated EDB.
      After BTXA injection, spontaneous activity appeared in both EDB muscles; but it
      appeared earlier and involved larger areas in the stimulated than in the
      nonstimulated EDB. In conclusion, short-term NS accelerates the effectiveness of
      intramuscular BTXA injections on the neuromuscular blockade in patients with
      spastic paraparesis and could induce a rapid and persistent improvement in
      spasticity. Its action probably arises mainly from low-frequency NS.

PMID- 15726577
TI  - Position-dependent levitation of the dominant arm after left parietal stroke: an
      unreported feature of posterior alien limb syndrome?
AB  - We describe a patient with an unreported feature of posterior alien limb
      phenomenon characterized by position-dependent levitation of the dominant arm
      exacerbated by tactile stimulation and associated with low-amplitude tremor of
      the fingers of the right hand in addition to a sensation of strangeness in the
      arm, secondary to a left parietal stroke.

PMID- 15726578
TI  - Quantifying maintenance requirements from the steady-state operation of a two
      phase partitioning bioscrubber.
AB  - An innovative method for directly and explicitly quantifying the maintenance
      energy requirements of pure cultures growing on volatile organic compound (VOC)
      substrates in a two-phase partitioning bioscrubber is described. Direct evidence
      of maintenance energy requirements of Achromobacter xylosoxidans Y234 is provided
      both through observed reductions in the macroscopic biomass-to-substrate yield
      with decreasing specific growth rates, but more remarkably through achievement of
      steady-state operation. The data conclusively show that maintenance activities do
      occur in the two-phase partitioning bioscrubber and clearly illustrate the
      importance of this phenomenon to the operation of this process, and similar
      bioreactor systems. While benzene was selected as the principal, sole substrate
      of interest in this study, ethylbenzene degradation experiments were also
      subsequently performed to illustrate and confirm the general applicability of the
      proposed technique, as well as the potential capabilities of the two-phase
      partitioning bioscrubber for the continuous treatment of waste gases containing
      various VOCs. The proposed method has been shown to generate maintenance energy
      estimates that are consistent with those obtained while employing more widely
      recognized estimation strategies, further validating its capabilities. The
      proposed steady-state mode also offers key operational advantages in terms of
      decreased disposal requirements in two-phase partitioning bioscrubbers. (c) 2005
      Wiley Periodicals, Inc.

PMID- 15726579
TI  - End-of-dose akinesia after a single intravenous infusion of the dopaminergic
      agonist piribedil in Parkinson's disease patients: a
      pharmacokinetic/pharmacodynamic, randomized, double-blind study.
AB  - This randomized, double-blind trial was designed to define the possible
      relationship between piribedil plasma concentrations and the decrease of the
      Unified Parkinson's Disease Rating Scale (UPDRS) motor score or the switch from
      off to on state after single intravenous infusion. Ten fluctuating patients with
      idiopathic Parkinson's disease (PD) received escalating doses of piribedil (2-16
      mg) and placebo. Starting from 2 mg, piribedil was effective in reducing the
      motor deficit (UPDRS, motor score) including akinesia at the first evaluation
      time point of 15 minutes, and in reversing off state of 7 of 10 patients. The
      doses were equally effective, although the effect was more sustained with the
      highest dose of 16 mg. Piribedil was well tolerated up to a 16-mg dose and
      pharmacokinetics were linear up to the 16-mg dose. Plasma levels of piribedil
      were not correlated to the motor score improvement or switch from off-->on. In
      conclusion, a short single infusion of piribedil at 2 to 16 mg was safe and
      effective in improving motor symptoms, including akinesia, of fluctuating PD
      patients.

PMID- 15726580
TI  - Parkinsonism in the course of HTLV-I-associated myelopathy.
AB  - Parkinsonian syndromes may represent a complication of viral infection. Human T
      cell lymphotropic virus I (HTLV-I) is a cause of a chronic myelopathy in which
      encephalic involvement has been also found. We report on the case of a 60-year
      old man with HTLV-I-associated myelopathy, complicated with bradykinesia, resting
      tremor, and cogwheel rigidity. These findings suggest that parkinsonian features
      may represent a neurological disorder associated with HTLV-I infection.

PMID- 15726581
TI  - Clinical and genetic evaluation in a French population presenting with primary
      focal dystonia.
AB  - Primary focal dystonia (PFD) is known to be a clinically and genetically
      heterogeneous group of movement disorders. To evaluate the frequency of familial
      focal dystonia in a French population presenting with PFD, we screened 197
      patients (150 index cases and 47 affected family members) presenting focal
      primary dystonia for the GAG deletion in the DYT1 gene and analyzed linkage to
      the DYT6, DYT7, and DYT13 loci in those who presented a family history. Fourteen
      families could be recruited and, among them 47 new symptomatic individuals could
      be identified by clinical examination. A group of 104 patients were without
      family history and 46 patients (30.7%) were found to have at least one first
      degree relative with dystonia. Mean age at onset was significantly later (55.4 +/
      14.0 years) in the blepharospasm group and earlier in patients with writer's
      cramp (35.8 +/- 14.0 years). The group of patients with family history showed a
      mean age at onset significantly earlier (39.2 +/- 18.0) than in patients without
      family history (47.4 +/- 14.4 years). Fourteen families demonstrated an autosomal
      mode of transmission and five families were studied further for genetic linkage
      analysis, but no significant linkage to one of the three loci could be observed.
      Our results illustrate the importance of genetic factors and the clinical
      heterogeneity of PFD. They indicate the existence of one or several as yet
      unmapped genes responsible for these diseases.

PMID- 15726582
TI  - Dopaminergic innervation of the human striatum in Parkinson's disease.
AB  - In Parkinson's disease (PD), dopaminergic input to the caudate nucleus and a band
      of putaminal tissue abutting the external globus pallidus seems well preserved on
      immunohistochemical staining for the dopamine transporter. Counting of
      dopaminergic terminals showed that terminal density in these regions in PD was
      the same as that in controls, which indicates that input is truly preserved and
      not a consequence of a compensatory upregulation of metabolism in a reduced pool
      of surviving terminals. When the branching pattern of dopaminergic axons coursing
      through the globus pallidus was examined, we found no evidence for increased
      axonal sprouting in PD that might have contributed to preservation of
      dopaminergic input to the putamen or caudate nucleus. Although terminal counting
      indicated that anatomic input was preserved to parts of the striatum, dopamine
      uptake site density in these regions was reduced significantly. This suggests
      that the impact of disease in these areas is more profound than was thought
      previously.

PMID- 15726584
TI  - Evolutionary-based grouping of haplotypes in association analysis.
AB  - Haplotypes incorporate more information about the underlying polymorphisms than
      do genotypes for individual SNPs, and are considered as a more informative format
      of data in association analysis. To model haplotypes requires high degrees of
      freedom, which could decrease power and limit a model's capacity to incorporate
      other complex effects, such as gene-gene interactions. Even within haplotype
      blocks, high degrees of freedom are still a concern unless one chooses to discard
      rare haplotypes. To increase the efficiency and power of haplotype analysis, we
      adapt the evolutionary concepts of cladistic analyses and propose a grouping
      algorithm to cluster rare haplotypes to the corresponding ancestral haplotypes.
      The algorithm determines the cluster bases by preserving common haplotypes using
      a criterion built on the Shannon information content. Each haplotype is then
      assigned to its appropriate clusters probabilistically according to the cladistic
      relationship. Through this algorithm, we perform association analysis based on
      groups of haplotypes. Simulation results indicate power increases for performing
      tests on the haplotype clusters when compared to tests using original haplotypes
      or the truncated haplotype distribution.

PMID- 15726585
TI  - Evolution and similarity evaluation of protein structures in contact map space.
AB  - Prediction of fold from amino acid sequence of a protein has been an active area
      of research in the past few years, but the limited accuracy of existing
      techniques emphasizes the need to develop newer approaches to tackle this task.
      In this study, we use contact map prediction as an intermediate step in fold
      prediction from sequence. Contact map is a reduced graph-theoretic representation
      of proteins that models the local and global inter-residue contacts in the
      structure. We start with a population of random contact maps for the protein
      sequence and "evolve" the population to a "high-feasibility" configuration using
      a genetic algorithm. A neural network is employed to assess the feasibility of
      contact maps based on their 4 physically relevant properties. We also introduce 5
      parameters, based on algebraic graph theory and physical considerations, that can
      be used to judge the structural similarity between proteins through contact maps.
      To predict the fold of a given amino acid sequence, we predict a contact map that
      will sufficiently approximate the structure of the corresponding protein. Then we
      assess the similarity of this contact map with the representative contact map of
      each fold; the fold that corresponds to the closest match is our predicted fold
      for the input sequence. We have found that our feasibility measure is able to
      differentiate between feasible and infeasible contact maps. Further, this novel
      approach is able to predict the folds from sequences significantly better than a
      random predictor.

PMID- 15726583
TI  - Colour remediation of pulp mill effluent using purified fungal cellobiose
      dehydrogenase: reaction optimisation and mechanism of degradation.
AB  - Cellobiose dehydrogenase purified from two different fungal sources was assessed
      for its ability to remove and/or reduce colour from pulp mill bleach plant
      effluent. Cellobiose dehydrogenase purified from Phanerochaete chrysosporium was
      shown to prefer acidic conditions and was consequently used to treat the acid
      effluent stream discharged from a pulp mill bleach plant, while an analogous
      enzyme originating from Humicola insolens preferred alkaline conditions, and was
      applied to the effluent discharged from the caustic sewer of the bleach plant.
      Both enzyme preparations were able to remove colour from their respective
      effluent sources to a comparable extent. Up to 50% of the effluent colour was
      removed within 4 days when treated under optimised conditions. Furthermore, it
      was also shown that this enzymatic approach was effective at removing colour
      generated by both softwood and hardwood resources. Mechanistically, it was shown
      that colour was removed from all molecular weight fractions, and the higher
      molecular weight material (>300 kDa) was concurrently preferentially degraded.
      Cellobiose dehydrogenase treatment of effluent did not target phenolic, stilbene,
      or alpha-carbonyl structures, but did affect the quinone content. Further
      investigations using model compounds confirmed these results, and subsequently
      showed that only the para-quinones with low substitution were reduced with
      cellobiose dehydrogenase.

PMID- 15726586
TI  - A pharmacophore-based evolutionary approach for screening selective estrogen
      receptor modulators.
AB  - We developed a pharmacophore-based evolutionary approach for virtual screening.
      This tool, termed the Generic Evolutionary Method for molecular DOCKing
      (GEMDOCK), combines an evolutionary approach with a new pharmacophore-based
      scoring function. The former integrates discrete and continuous global search
      strategies with local search strategies to expedite convergence. The latter,
      integrating an empirical-based energy function and pharmacological preferences
      (binding-site pharmacological interactions and ligand preferences),
      simultaneously serves as the scoring function for both molecular docking and
      postdocking analyses to improve screening accuracy. We apply pharmacological
      interaction preferences to select the ligands that form pharmacological
      interactions with target proteins, and use the ligand preferences to eliminate
      the ligands that violate the electrostatic or hydrophilic constraints. We
      assessed the accuracy of our approach using human estrogen receptor (ER) and a
      ligand database from the comparative studies of Bissantz et al. (J Med Chem
      2000;43:4759-4767). Using GEMDOCK, the average goodness-of-hit (GH) score was
      0.83 and the average false-positive rate was 0.13% for ER antagonists, and the
      average GH score was 0.48 and the average false-positive rate was 0.75% for ER
      agonists. The performance of GEMDOCK was superior to competing methods such as
      GOLD and DOCK. We found that our pharmacophore-based scoring function indeed was
      able to reduce the number of false positives; moreover, the resulting
      pharmacological interactions at the binding site, as well as ligand preferences,
      were important to the screening accuracy of our experiments. These results
      suggest that GEMDOCK constitutes a robust tool for virtual database screening.

PMID- 15726587
TI  - Definitive radiotherapy with interstitial implant boost for squamous cell
      carcinoma of the tongue base.
AB  - BACKGROUND: The purpose of this study was to examine the long-term outcome of a
      cohort of patients with unresected base of tongue carcinoma who received
      interstitial brachytherapy after comprehensive external beam radiation therapy.
      METHODS: Between 1983 and 2000, 122 patients with primary or recurrent squamous
      cell carcinoma of the oropharynx or oral cavity received interstitial
      brachytherapy as part of their overall management. Forty patients had primary,
      unresected carcinoma of the base of tongue and are the subjects of this analysis.
      The median age was 54 years. Fifty-four percent had T3 or T4 disease, and 70% had
      clinical or radiographic lymphadenopathy. Twenty-four (60%) received two to three
      cycles of neoadjuvant chemotherapy. The oropharynx, bilateral neck, and
      supraclavicular fossae were comprehensively irradiated, and the tongue base
      received a median external beam dose of 61.2 Gy (50-72 Gy). The primary site was
      then boosted with an interstitial 192Iridium implant by use of a gold-button
      single-strand technique and three-dimensional treatment planning. The dose rate
      was prescribed at 0.4 to 0.5 Gy/hr. The median implant dose was 17.4 Gy (9.6-24
      Gy) and adjusted to reach a total dose to the primary tumor of 80 Gy. N2 to 3
      disease was managed by a planned neck dissection performed at the time of the
      implant. RESULTS: The median follow-up for all patients was 56 months, and the
      overall survival rates were 62% at 5 years and 27% at 10 years. The actuarial
      primary site control was 78% at 5 years and 70% at 10 years. The overall survival
      and primary site control were independent of T classification, N status, or
      overall stage. Systemic therapy was associated with an improvement in overall
      survival (p = .04) and a trend toward increased primary site control with greater
      clinical response. There were seven documented late effects, the most frequent
      being grade 3 osteonecrosis (n = 2), grade 2 swallowing dysfunction (n = 2),
      trismus (n = 2), and chronic throat pain (n = 1). CONCLUSIONS: In an era of
      greatly improved dose distributions made possible by three-dimensional treatment
      planning and intensity-modulated radiation therapy, brachytherapy allows a highly
      conformal dose to be delivered in sites such as the oropharynx. If done properly,
      the procedure is safe and delivers a dose that is higher than what can be
      achieved by external beam radiation alone with the expected biologic advantages.
      The long-term data presented here support an approach of treating advanced tongue
      base lesions that includes interstitial brachytherapy as part of the overall
      management plan. This approach has led to a 78% rate of organ preservation at 5
      years, with a 5% incidence of significant late morbidity (osteonecrosis) that has
      required medical management.

PMID- 15726588
TI  - Analysis of GTPases carrying hydrophobic amino acid substitutions in lieu of the
      catalytic glutamine: implications for GTP hydrolysis.
AB  - Ras superfamily GTP-binding proteins regulate important signaling events in the
      cell. Ras, which often serves as a prototype, efficiently hydrolyzes GTP in
      conjunction with its regulator GAP. A conserved glutamine plays a vital role in
      GTP hydrolysis in most GTP-binding proteins. Mutating this glutamine in Ras has
      oncogenic effects, since it disrupts GTP hydrolysis. The analysis presented here
      is of GTP-binding proteins that are a paradox to oncogenic Ras, since they have
      the catalytic glutamine (Glncat) substituted by a hydrophobic amino acid, yet can
      hydrolyze GTP efficiently. We term these proteins HAS-GTPases. Analysis of the
      amino acid sequences of HAS-GTPases reveals prominent presence of insertions
      around the GTP-binding pocket. Homology modeling studies suggest an interesting
      means to achieve catalysis despite the drastic hydrophobic substitution replacing
      the key Glncat of Ras-like GTPases. The substituted hydrophobic residue adopts a
      "retracted conformation," where it is positioned away from the GTP, as its role
      in catalysis would be unproductive. This conformation is further stabilized by
      interactions with hydrophobic residues in its vicinity. These interacting
      residues are strongly conserved and hydrophobic in all HAS-GTPases, and
      correspond to residues Asp92 and Tyr96 of Ras. An experimental support for the
      "retracted conformation" of Switch II arises from the crystal structures of Ylqf
      and hGBP1. This conformation allows us to hypothesize that, unlike in classical
      GTPases, catalytic residues could be supplied by regions other than the Switch II
      (i.e., either the insertions or a neighboring domain).

PMID- 15726590
TI  - Effects of hydroxyurea in a population of Brazilian patients with sickle cell
      anemia.
AB  - Fetal hemoglobin (HbF) inhibits the polymerization of sickle hemoglobin,
      modulating the clinical features of sickle cell anemia (SCA). Hydroxyurea (HU)
      therapy can increase the HbF level, although its production can be influenced by
      genetic determinants. Twenty-two Brazilian SCA patients were evaluated over 5
      years before and after HU use. We analyzed (1) betaS haplotype; (2) patient
      characteristics; and (3) toxicity. No differences between age, sex, and HU
      response were observed. We found 40.9% of homozygous for Bantu haplotype, and, in
      contrasting to other trials, we observed HbF level increase in this group (3.84
      9.08 g/dL, P=0.003). Adverse effects were rare. Labyrinthitis was observed in 2
      (9.10%) patients after HU use, although this complication had not been described
      before.

PMID- 15726589
TI  - Survival outcome of patients with nasopharyngeal carcinoma with first local
      failure: a study by the Hong Kong Nasopharyngeal Carcinoma Study Group.
AB  - BACKGROUND: The purpose of this article is to report the overall survival (OS)
      outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who
      received salvage treatment and to identify prognostic factors for OS. METHODS:
      Between January 1996 and December 2000, 2915 patients received primary
      radiotherapy (RT) with or without chemotherapy for nonmetastatic NPC. At a median
      follow-up of 3.1 years, 319 patients had developed local failure as the first
      failure, with or without synchronous regional/distant failure. OS was calculated
      from the start of primary RT. Univariate and multivariate analyses were performed
      to identify prognostic factors for OS in patients with isolated local failure.
      RESULTS: The T classification distribution of the local failure (rT
      classification) was as follows: 68 (21%) rT1 to T2a, 92 (29%) rT2b, 82 (26%) rT3,
      and 77 (24%) rT4. The rT classification was the same as the initial T
      classification in 82% of patients. Two hundred seventy-five patients (86%) had
      isolated local failure, and 232 (84%) of them did not have any distant metastasis
      or regional failure develop during follow-up. Salvage treatment was given to 200
      patients (73%) with isolated local failure. One hundred fifty-nine patients (80%)
      received reirradiation (108 external beam RT [EBRT], 44 brachytherapy, and seven
      EBRT plus brachytherapy), 22 patients (11%) underwent nasopharyngectomy with or
      without postoperative RT, and 19 patients (9%) were treated with chemotherapy
      alone. Four patients died of RT complications, and one died of chemotherapy
      toxicity in the absence of active NPC. The 3-year actuarial OS for patients with
      isolated local failure was 74%. On multivariate analysis, advanced initial T
      classification (hazard ratio [HR], 1.44; p = .0006) and the use of salvage
      treatment (HR, 0.54; p = .0038) were independent prognostic factors. For the
      subgroups of patients who had the same recurrent and initial T classification,
      salvage treatment was associated with improved OS only in the subgroup with T1 to
      T2 local failure (n = 127; p = 0.0446), but not in the subgroups with T3 (n = 48)
      or T4 (n = 54) disease. CONCLUSIONS: Most patients with first local failure have
      localized disease. Salvage treatment is feasible in most of the patients with
      clinically isolated local failure. Patients who had early initial T
      classification have a more favorable prognosis. Subgroup analysis suggests that
      salvage treatment only prolongs survival in patients with T1 to T2 recurrent
      disease.

PMID- 15726591
TI  - Hb Q India: is it always benign?

PMID- 15726592
TI  - Intravascular T-cell lymphoma with bowel involvement: case report and literature
      review.
AB  - Intravascular lymphoma (IVL) is a rare form of non-Hodgkin lymphoma characterized
      by massive proliferation of large, neoplastic cells in small- and medium-sized
      blood vessels. Most cases of IVL are of B-cell immunophenotype; fewer than 15
      cases of T-cell IVL have been reported. A 23-year-old male presented with acute
      abdominal pain, fever, and tender lower abdomen. Pathology at laparotomy revealed
      infiltration of colonic vessels with large lymphoid cells compatible with IVL. We
      reviewed all cases of IVL diagnosed at the Queen Elizabeth II Health Sciences
      Centre in Halifax, Nova Scotia, from August 1992 to August 2002. A literature
      review was also performed. Five additional cases of IVL were identified at this
      institution during a 10-year period. Three patients presented with neurological
      symptoms, and two with abdominal pain. In 4 of 5 cases, patients died of lymphoma
      within 3 months of presentation; one patient experienced a 10-month remission.
      While visceral involvement with IVL is common at autopsy, IVL presenting as an
      acute abdomen in an immunocompetent patient has not previously been described.
      Among the 15 cases of T-cell IVL reported in the literature, only two occurred in
      people under age 30. Given the rarity of T-cell IVL, it is remarkable that three
      cases of T-cell IVL have been diagnosed at our institution during a 10-year
      period.

PMID- 15726593
TI  - CD5+ Epstein-Barr virus-positive intravascular large B-cell lymphoma in the
      uterus co-existing with huge myoma.
AB  - A 42-year-old female underwent hysterectomy because of a huge uterine mass.
      Histologically, she was diagnosed as having intravascular lymphoma co-existing
      with myoma uteri. Lymphoma cells were large in size and were positive for CD5,
      CD20, CD45, CD79a, lambda light chain, and EBV but were negative for CD3 and
      cyclin D1. No other organs except for the adjoining bilateral ovaries seemed to
      be affected by the lymphoma cells. She received the combination chemotherapy
      (cyclophosphamide, doxorubicin, vincristine, and prednisolone) together with
      rituximab and has been well without definite disease progression. So far, this is
      the first case of CD5+ EBV+ intravascular large B-cell lymphoma (CD5+ EBV+ IVLBL)
      in the uterus of a patient who was incidentally diagnosed and successfully
      treated.

PMID- 15726594
TI  - Immune heparin-induced thrombocytopenia can occur in patients receiving
      clopidogrel and aspirin.
AB  - Platelet adenosine diphosphate (ADP) receptors may play a role in potentiating
      platelet activation induced by IgG from patients with immune heparin-induced
      thrombocytopenia (HIT), as shown by previous studies using the ADP receptor
      antagonists AR-C66096 and ticlopidine. Consistent with these observations, we
      found that platelet activation by HIT sera is also significantly reduced in
      patients receiving clopidogrel, an ADP receptor antagonist prodrug now in wide
      clinical use. Despite these in vitro and ex vivo findings, we observed two
      patients develop acute HIT while receiving both clopidogrel and aspirin: both
      patients' sera tested strongly positive in a heparin-dependent washed platelet
      activation assay (100% serotonin release) and PF4/heparin-enzyme-immunoassay
      (2.594 and 2.190 absorbance units). Both patients also developed HIT-associated
      clinical sequelae (acute systemic reaction postintravenous heparin bolus;
      thrombotic stroke) in association with their episode of HIT. We conclude that
      combined therapy with aspirin and clopidogrel does not necessarily protect
      against clinical HIT, at least in patients with HIT antibodies that have strong
      platelet-activating characteristics.

PMID- 15726595
TI  - Prospective evaluation of a new platelet glycoprotein (GP)-specific assay
      (PakAuto) in the diagnosis of autoimmune thrombocytopenia (AITP).
AB  - Assays measuring platelet-associated immunoglobulin G (PAIgG), while highly
      sensitive, lack specificity in diagnosing autoimmune thrombocytopenia (AITP). We
      prospectively evaluated a new commercially available glycoprotein (GP)-specific
      assay, the PakAuto (GTI, Brookfield, WI), for its clinical usefulness in
      distinguishing immune from nonimmune thrombocytopenia (TP), in 216 patients with
      autoimmune TP (both primary "idiopathic" and "secondary") and 46 patients with TP
      due to other causes. This assay is designed to detect both platelet-associated
      (direct assay) and plasma (indirect assay) antiplatelet antibodies specific for
      GPs IIb/IIIa, Ib/IX, and Ia/IIa. The mean platelet counts of the immune (79 +/- 7
      x 10(9)/L) and nonimmune groups (78 +/- 7 x 10(9)/L), were similar (P=0.95). The
      direct assay was positive in 114/216 patients with AITP (53%), and 13/46 with
      nonimmune TP (28%). Among the AITP group, the majority (61%) of patients with
      positive test results had autoantibodies reactive against all three GP targets.
      The sensitivity, specificity, positive, and negative predictive values for the
      direct PakAuto were 53%, 72%, 90%, and 24%, respectively, comparable to
      previously published experience of GP-specific assays. However, in some cases of
      TP due to nonimmune cause, the PakAuto was highly specific. Only 3 of 22 patients
      with gestational and 1 of 8 with familial/congenital TP had a positive direct
      assay, indicating that the test may be particularly useful for excluding an
      immune etiology for TP in certain patient subgroups.

PMID- 15726596
TI  - Sickle cell vaso-occlusive crisis induces the release of circulating serum heat
      shock protein-70.
AB  - Inflammation may play an important role in the pathophysiology of sickle cell
      disease (SCD), and recent studies have identified the 70-kDa heat shock protein
      (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a
      significant increase in circulating serum Hsp70 level in SCD during vaso
      occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05)
      and a significant increase in Hsp70 levels in SCD at baseline compared with
      normal controls (P <0.05). Taken together, these results indicate that
      circulating serum Hsp70 might be a marker for VOC in SCD.

PMID- 15726597
TI  - Cutaneous reactions to imatinib mesylate treated by topical steroid.

PMID- 15726598
TI  - Barriers and motivators to blood and cord blood donations in young African
      American women.
AB  - The primary aim of this study was to assess potential barriers and motivators to
      blood and cord blood donation among African-American women. A telephone survey of
      African-American women, ages 18-30 years, in the St. Louis metropolitan area was
      performed. The survey was administered by trained telemarketing personnel using a
      Computer-Assisted Direct Interview (CADI) system. One hundred sixty-two women
      were surveyed. Common barriers to blood donation were inconvenience of donor
      sites (19%), fear of needles (16%), and too much time required to donate (15%).
      Potential motivators were increasing awareness of need for blood (43%),
      increasing the number of convenient donor locations (19%), and encouragement by
      spiritual leaders to have blood drives at their church (17%). Lack of awareness
      was the only identified barrier to cord blood donation. Most women surveyed (88%)
      indicated that they definitely or probably would donate cord blood. Strategies to
      increase the proportion of African-American blood and cord blood donations may
      include educating potential donors about the process and benefits of donation to
      particular patient populations and engaging church leadership in supporting blood
      and cord blood donations.

PMID- 15726599
TI  - Iron deficiency: a concise review.
AB  - Iron deficiency is a major worldwide health problem. There is recent evidence
      that the anemia is only the last manifestation of the syndrome and that symptoms
      occur before the anemia is manifest. Advances in outlining the physiology of iron
      deficiency have been made, gaps remain in the current understanding. While oral
      iron supplement remains the mainstay, some indications for the intravenous
      administration have developed. This review will highlight the epidemiology,
      physiology, clinical presentation, and treatment options.

PMID- 15726600
TI  - Venous thromboembolism prophylaxis in medically ill patients and the development
      of strategies to improve prophylaxis rates.
AB  - Venous thromboembolism (VTE) is common but often unrecognized in medically ill
      patients. Over the past 5 years, three large-scale placebo-controlled trials
      enrolling a total of 5500 medically ill patients have highlighted the risk of VTE
      in this group. These trials have helped to define a specific at-risk patient
      profile, including those admitted to the hospital with severe congestive heart
      failure, respiratory illness, acute infection, and inflammatory bowel disease. We
      performed a retrospective review of patients admitted to the medical service at
      our tertiary care center to define how common the at-risk medical patient is and
      to evaluate and improve prophylaxis rates in this patient group. The study was
      conducted in two phases. Based on admission characteristics, patients were
      stratified into high-risk or low-risk groups for the development of VTE. During
      the pre-intervention phase, 75% of patients admitted to the medical service were
      characterized as increased risk for VTE, yet only 43% of these high-risk patients
      received prophylaxis of any sort. After interventions designed to increase
      awareness of VTE, we conducted a second review period. In this post-intervention
      phase, where 79% of patients were at risk for VTE, prophylaxis rates improved to
      72%. Based on these results, we conclude that the majority of patients admitted
      to the medical service at our tertiary care center constitute a high-risk
      population that warrants consideration for VTE prophylaxis. Implementation of
      strategies to improve prophylaxis rates, including educational sessions and risk
      stratification guidelines, can be successful and improve identification and
      prophylaxis of this population.

PMID- 15726601
TI  - Expression of IAP-family proteins in adult acute mixed lineage leukemia (AMLL).
AB  - Inhibitor of apoptosis protein (IAP)-family proteins suppress apoptotic signaling
      in normal/neoplastic cells in various settings. To determine the apoptosis
      resistant mechanism in adult acute mixed lineage leukemia (AMLL) with
      biphenotypic blasts responsible for resistance against chemotherapy, the
      expression levels of IAP-family proteins in AMLL bone marrow cells were analyzed
      by quantitative RT-PCR. The overall expression levels of IAPs were higher than
      those in control, AML, and ALL cells. A significant difference for the expression
      of survivin was observed between AMLL and AML (P <0.05), and differences between
      AMLL and ALL were significant for the expression of survivin (P <0.05), NAIP (P
      <0.05), and XIAP (P <0.05). These findings suggest that higher expression of
      various IAPs is associated with the chemotherapy-resistant nature of this
      specific type of leukemia.

PMID- 15726602
TI  - Current views in HTLV-I-associated adult T-cell leukemia/lymphoma.
AB  - Epidemiological studies have demonstrated that the relative percentage of
      malignant lymphoid proliferations varies widely according to geographical
      location and ethnic populations. HTLV-I is the etiological agent of adult T-cell
      leukemia/lymphoma (ATLL) and is also associated with cutaneous T-cell lymphoma
      (CTCL). However, a definite role of HTLV-I in mycosis fungoides (MF) and/or
      Sezary syndrome (SS) remains controversial. While most HTLV-I-infected
      individuals remain asymptomatic carriers, 1-5% will develop ATLL, an invariably
      fatal expansion of virus-infected CD4+ T cells. This low incidence and the long
      latency period preceding occurrence of the disease suggest that additional
      factors are involved in development of ATLL. In this review, diagnosis, clinical
      features, and molecular pathogenesis of HTLV-I are discussed.

PMID- 15726603
TI  - Hemophagocytosis evolving into acute lymphoblastic leukemia.

PMID- 15726604
TI  - Coinheritance of BRCA1 and BRCA2 mutations with Fanconi anemia and Bloom syndrome
      mutations in Ashkenazi Jewish population: possible role in risk modification for
      cancer development.
AB  - Fanconi anemia (FA) and Bloom syndrome (BS) are rare autosomal recessive genetic
      disorders manifesting in childhood, with a predisposition to cancer development
      in adolescence and adulthood. Both syndromes are relatively prevalent among the
      Ashkenazi Jewish population, and, in both syndromes, mutations specific to this
      population have been identified. Similarly, unique Ashkenazi mutations were found
      in the genes BRCA1 and BRCA2. These two genes, when mutated, play important roles
      in familial breast and ovarian carcinogenesis. The genes involved in the
      pathogenesis of the FA and BS belong to the general class of instability genes.
      Heterozygosity for the FA gene has no known promalignant potential, while the BS
      mutation carrier state was associated with an increased frequency of colorectal
      cancer. The especially frequent carrier state among the Ashkenazi Jewish
      population coupled with the high prevalence of BRCA1 and BRCA2 in the same
      population has led us to search for coinheritance affecting the potential for
      cancer development. One hundred Ashkenazi women with known BRCA1 and BRCA2
      mutations were screened for the FA mutation IVS4+4 A-->T and the BS mutation
      blm(Ash). Our results indicate that there is an increased prevalence of both FA
      and BS mutation carriers among the population studied compared with the general
      Ashkenazi population (prevalence of FA mutation 4/100 women [4%] as compared to
      35/3104 previously published controls [1.1%], P=0.031, and for BS mutation 3/100
      [3.2%] as compared to 36/4001 [0.9%], P=0.058). There was no statistically
      significant effect of the coinheritance on cancer prevalence, type of cancer, or
      age of cancer onset. Coinheritance of FA and/or BS mutations seems to be more
      prevalent among BRCA mutation carriers, but a larger study encompassing more
      women may help in clarifying this issue.

PMID- 15726605
TI  - Remission of natural-killer cell lymphoma of the liver with anti-hepatitis C
      therapy.
AB  - Non-Hodgkin lymphomas (NHL) consist of a diverse group of lymphoproliferative
      neoplasms with unique patterns of biology, behavior, and differing responses to
      therapy. A rare subtype of malignancy arising from cells of putative natural
      killer (NK) origin is being recognized as a distinct clinicopathological entity.
      Viruses including hepatitis C have been reported in association with various
      types of NHL but not the NK-cell subtype. We hereby report a unique case of a
      patient with hepatitis C who developed hepatic NK-cell lymphoma and chronic NK
      cell leukemia. Interestingly, we observed clinical and radiologic remission of
      the neoplasm following treatment with anti-hepatitis C therapy.

PMID- 15726606
TI  - Strokes after intravenous gamma globulin: thrombotic phenomenon in patients with
      risk factors or just coincidence?
AB  - We report the case of an 82-year-old woman with a diagnosis of chronic
      inflammatory demyelinating polyneuropathy (CIDP) for more than 10 years, who
      developed an ischemic stroke during infusion of immunoglobulin (IVIG). She had
      received IVIG intermittently for several years, and the previous 86 doses were
      well tolerated. Thromboembolism was suspected based on magnetic resonance
      angiogram and on further extension of the deficit after 4 days of evolution.
      Strokes were associated with the use of IVIG in different clinical circumstances.
      Pre-existing thrombogenic risk factors should be carefully considered for
      patients undergoing treatment with IVIG. Clinical evaluation, with attention to
      history, a focused vascular work-up, and looking for markers of dehydration, can
      identify the high-risk patient for whom a careful analysis of the risk/benefit
      ratio is warranted.

PMID- 15726607
TI  - Treatment, outcome, and cost of care in children with idiopathic thrombocytopenic
      purpura.
AB  - Data were reviewed on treatment patterns, outcome, and hospital charges for
      children with idiopathic thrombocytopenic purpura (ITP). Records of 186 children
      with ITP, seen between January 1997 and April 2001, were reviewed. Hospital
      charges for initial management and first re-treatment were calculated by
      combining physician, hospital, and pathology charges. Anti-D immune globulin
      [anti-D IG] was used in 32.3%, intravenous immune globulin [IVIG] in 22.6%,
      steroids in 22.6%, combination therapies in 8%, and 14.5% were observed. Two
      patients had CNS bleeding, one with intraventricular hemorrhage at diagnosis, and
      the other with a parietal bleed 1 year from diagnosis. There was no significant
      differences in time to reach platelet counts of 20, 50, or 150 (x 10(9)/L) across
      different treatment groups. There was no significant difference in median charges
      for the IVIG and anti-D IG groups for the initial treatment of ITP. However, the
      IVIG was significantly more expensive than steroids or observation. Charges for
      the anti-D IG group were higher than the observation group but not the steroid
      group. After drug charges were excluded, patients in the IVIG group had
      statistically higher charges compared to patients in anti-D IG group. Almost half
      the patients were re-treated. There was no significant difference between anti-D
      IG, IVIG, and steroid groups when initial and re-treatment charges were combined.
      The observation group remained least expensive. Outcome for children with ITP is
      similar regardless of initial management. There is not a statistically
      significant difference in hospital charges between patients treated with anti-D
      IG and IVIG. The IVIG-treated group tends to be more costly, but this is not due
      to drug charges. Re-treatment is common and decreases the difference in patient
      charges among initial therapies.

PMID- 15726608
TI  - Disseminated colon cancer with severe peripheral blood eosinophilia and elevated
      serum levels of interleukine-2, interleukine-3, interleukine-5, and GM-CSF.

PMID- 15726609
TI  - Hydrophobic tendency of polar group hydration as a major force in type I
      antifreeze protein recognition.
AB  - The random network model of water quantitatively describes the different
      hydration heat capacities of polar and apolar solutes in terms of distortions of
      the water-water hydrogen bonding angle in the first hydration shell (Gallagher
      and Sharp, JACS 2003;125:9853). The distribution of this angle in pure water is
      bimodal, with a low-angle population and high-angle population. Polar solutes
      increase the high-angle population while apolar solutes increase the low-angle
      population. The ratio of the two populations quantifies the hydrophobicity of the
      solute and provides a sensitive measure of water structural distortions. This
      method of analysis is applied to study hydration of type I thermal hysteresis
      protein (THP) from winter flounder and three quadruple mutants of four threonine
      residues at positions 2, 13, 24, and 35. Wild-type and two mutants (VVVV and
      AAAA) have antifreeze (thermal hysteresis) activity, while the other mutant
      (SSSS) has no activity. The analysis reveals significant differences in the
      hydration structure of the ice-binding site. For the SSSS mutant, polar groups
      have a typical polar-like hydration, that is, more high-angle H-bonds than bulk
      water. For the wild-type and active mutants, polar groups have unusual, very
      apolar-like hydration, that is, more low-angle H-bonds than bulk water. This
      pattern of hydration was seen previously in the structurally distinct type III
      THPs (Yang & Sharp Biophys Chem 2004;109:137), suggesting for the first time a
      general mechanism for different THP classes. The specific shape, residue size,
      and clustering of both polar and apoler groups are essential for an active ice
      binding surface.

PMID- 15726610
TI  - Pre-operative chemoradiotherapy with oral tegafur-uracil and leucovorin for
      rectal cancer.
AB  - BACKGROUND: To evaluate the efficacy and toxicity of pre-operative radiotherapy
      (RT) combined with oral tegafur-uracil (UFUR) plus leucovorin (LV) in rectal
      cancer. PATIENTS: Sixty-five patients with rectal adenocarcinoma (clinical staged
      T2-4N0-2M0) received pelvic RT of 45 Gy in 20 fractions over 28 days. Concurrent
      chemotherapy consisted of UFUR (200 mg/m(2)/day) and LV (45 mg/day) on day 1-28.
      UFUR (250 mg/m(2)/day) and LV were continued on day 36-63. Surgery was performed
      on day 70. RESULTS: Sixty-three patients completed the concurrent
      chemoradiotherapy (CCRT) and 56 received curative or palliative surgery. Among
      the 52 patients receiving curative resection, downstaging (DS) occurred in 39
      (75%), pathological complete response in 13 (25%), and sphincter preservation was
      achieved in 16 of 29 (55%) with lower-seated tumors. With a median follow-up time
      of 33 months, local failure developed in 4 (8%) and distant metastases occurred
      in 7 (14%). The 3-year overall survival was 92% and disease-free survival 76%.
      For all 65 patients, grade 3-4 diarrhea developed in 6 (9%) and grade 3-4
      leucopenia observed in 2 (3%). CONCLUSIONS: Oral UFUR + LV administered with pre
      operative RT are effective in tumor DS, pathological complete response, and
      sphincter preservation with tolerable toxicity in rectal cancer.

PMID- 15726611
TI  - Intra-arterial bolus octreotide administration during Whipple procedure in
      patients with fragile pancreas: a novel technique for safer
      pancreaticojejunostomy.
AB  - BACKGROUND AND OBJECTIVES: Leakage from the pancreaticojujenostomy is the most
      serious complication of Whipple. Pancreatic fistula rate is higher in cases of
      fragile pancreas often seen in duodenal carcinomas and carcinomas of the ampulla
      of Vater. Octreotide administration has been used for the prevention of fistula
      formation through the subcutaneous route. Due to its physiologic effects to the
      pancreatic parenchyma the intra-arterial administration of octreotide could
      provide tissue hardening that allows for a technically easier anastomosis while
      maintaining its protective role for fistula formation. METHODS: Octreotide was
      injected directly into the distal part of the gastroduodenal artery (GDA) in four
      patients undergoing Whipple for histologically proven periampullary cancer.
      RESULTS: Tissue hardening after octreotide administration was evident not only in
      surgeons' hands but in the intra-operative ultrasound as well. The three patients
      were discharged on day 9, 11, and 13; they had an uneventful postoperative
      course, while one patient had a minor bile leak from the choledojejunal
      anastomosis and was discharged on day 22. CONCLUSIONS: The intra-arterial
      administration of octreotide during Whipple is a safe procedure and provides
      tissue hardening thus making the performance of the anastomosis technically
      easier. The actual benefit in terms of morbidity, mortality, and fistula rate are
      to be further evaluated.

PMID- 15726612
TI  - Correlation between histological effects on the main tumors and nodal status
      after chemoradiotherapy for squamous cell carcinoma of the esophagus.
AB  - BACKGROUND AND OBJECTIVES: Although the histological effectiveness of
      preoperative chemoradiotherapy against the main tumor is reported to be the
      strongest prognostic factor for patients with esophageal cancer, it remains
      unknown whether such chemoradiotherapy is equally effective against metastatic
      lymph nodes. METHODS: We studied 103 consecutive patients with esophageal cancer,
      who were given preoperative chemoradiotherapy followed by surgery. The
      histological effectiveness against the main tumor of the chemoradiotherapy was
      correlated with lymph mode metastasis and other clinico-pathological factors.
      RESULTS: The histological effectiveness against the main tumor was grade 3 in 26
      patients, grade 2 in 49 and grade 1 in 28. The number of pathological node
      negative patients was 21 (80.8%), 19 (38.8%), and 7 (25.0%) in those having grade
      3, 2, and 1 responses of their main tumors, respectively. The average number of
      pathological metastatic lymph nodes was 0.19, 1.4, and 4.4 in patients with grade
      3, 2, and 1 responses, respectively. Endoscopic biopsy after the
      chemoradiotherapy could not accurately diagnose the pathological complete
      response (CR) of the main tumors, with a high false negative rate (60.9%).
      CONCLUSIONS: The effects of chemoradiotherapy against main tumors significantly
      correlated with nodal status. Most patients with main tumors of pathological CR
      are node-negative. Patients with a grade 2 response have at most a few positive
      nodes. Surgery would be most beneficial for such patients.

PMID- 15726615
TI  - Prognostic indicators in locally advanced gastric cancer (LAGC) treated with
      preoperative chemotherapy and D2-gastrectomy.
AB  - BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy is increasingly considered an
      effective treatment option for patients with gastric carcinoma. Aim of the study
      is to evaluate the prognostic significance of the pathological response and of
      known prognostic factors in a group of accurately staged locally advanced gastric
      cancer (LAGC) patients. METHODS: Thirty-three patients with LAGC, staged by
      laparoscopy, underwent D2-gastrectomy after preoperative chemotherapy. Survival
      was calculated by Kaplan-Meier method and differences were assessed by the Log
      rank and Breslow test. Multivariate analysis was performed using the Cox
      proportional hazard model in backward stepwise regression. RESULTS: Curative
      resection (R0) was achieved in 81.8% of patients. A complete or subtotal
      pathological response was documented in 3 and 6%, respectively. Nineteen out of
      thirty-three (57.6%) patients were alive and 16 of them were free of relapse at
      last follow-up. Survival rates were 81, 67, and 59% at 12, 24, and 36 months,
      respectively. At univariate and multivariate analysis, only R0 resection was
      found to be an independent prognostic factor. CONCLUSIONS: In the current study,
      R0 resection is the most important prognostic factor for resectable LAGC;
      according to our results we feel encouraged to consider neoadjuvant chemotherapy
      a promising modality for increasing the R0-percentage of gastric carcinoma
      patients who could benefit from a curative surgery.

PMID- 15726616
TI  - Cervical excision using superior sternum lifting method for large mediastinal
      parathyroid gland.

PMID- 15726617
TI  - Insurgent micrometastases: sleeper cells and harboring the enemy.

PMID- 15726618
TI  - Immunoreactive estrogen receptor in breast tumor and adjacent tissue: association
      with clinicopathological characteristics in Indian population.
AB  - BACKGROUND AND OBJECTIVES: Estrogen receptor (ER) status serves as an important
      prognostic marker in the management of breast cancer. The level of ER in breast
      tumor is different in different racial and ethnic groups. In the present study,
      we have compared the ER levels in breast tumor and adjacent normal tissue in
      Indian sub-population. METHODS: Immunoreactive ER was measured by enzyme
      immunoassay in breast tumors (ERt) and adjacent area (ERa) derived from 45 breast
      cancer patients from North India. Clinical parameters like age, menopausal
      status, tumor stage, recurrence and treatment status were recorded. RESULTS: A
      significant positive correlation was observed between the levels of ERt and ERa
      (r = 0.386, P = 0.009). While the ERt levels increased with advancing age (P =
      0.087), the ERa levels did not change in different age groups. The ERt levels
      negatively correlated with tumor stage and recurrence (r = -0.263, P = 0.110 and
      r = -0.202, P = 0.189). A significant negative correlation was also observed
      between the ERa levels and tumor recurrence (r = -0.337, P = 0.025). Further, the
      ERt positivity was higher than the ERa positivity. The clinical characteristics
      like age, tumor stage, metastasis, recurrence, and treatment status did not
      correlate with ERt and ERa positivity. CONCLUSIONS: The present study shows that
      the levels of ERt and ERa positively correlate and both ERt and ERa show negative
      correlation with tumor recurrence.

PMID- 15726621
TI  - Favorable outcome of Ewing sarcoma family tumors to multiagent intensive
      preoperative chemotherapy: a single institution experience.
AB  - BACKGROUND: Aim of our study was to evaluate the efficacy of multiagent intensive
      preoperative chemotherapy in patients with Ewing sarcoma family tumors (ESFT), in
      order to succeed a better percentage of necrosis before surgical resection.
      PROCEDURE: Eighteen patients with ESFT were treated with the same multiagent
      intensive preoperative protocol. 5/18 patients had bone Ewings sarcoma (EWS) and
      13/18 had peripheral primitive neuroectodermal tumor (PNET). None had metastases
      at diagnosis. Chemotherapy consisted of 5 or 6 cycles with vincristine,
      cisplatin, cyclophosphamide, and Adriamycin, followed by 12 cycles of
      vincristine, cyclophosphamide, and actinomycin-D. Five patients with EWS
      underwent total resection after 5-6 cycles of preoperative chemotherapy and
      prosthetic replacement was performed in two of them. In 3/13 patients with PNET
      the tumor was resected at diagnosis and in 1/13 after 5 cycles of chemotherapy,
      while 9/13 patients received chemotherapy only and/or radiotherapy. RESULTS: In
      patients with EWS, the histologic specimens of the resected tumors showed that
      tissue necrosis was 100% in four patients and 95% in one patient. The good
      histologic response reflects the effectiveness of this regimen in all ESFT. No
      patient had topical recurrence or developed metastatic disease during follow-up
      period (2-13 years, mean time 7.4 years). All patients had the scheduled cycles
      without delays or dose reductions. There were no major side effects of
      chemotherapy. CONCLUSIONS: The intensive chemotherapy schedule, comprising of 5-6
      cycles preoperatively, seems to maximize the percentage of tumor necrosis, thus
      improving outcome. Our study implies that this combined therapy may improve the
      prognosis of ESFT.

PMID- 15726622
TI  - Factors predicting survival in stage IV colorectal carcinoma patients after
      palliative treatment: a multivariate analysis.
AB  - BACKGROUND: The prognostic impact of primary tumor resection in patients
      presenting with unresectable synchronous metastases from colorectal carcinoma
      (CRC) is not well established. In the present study, we analyzed fifteen factors
      to define the value of primary tumor resection with regard to prognosis. PATIENTS
      AND METHODS: We identified 186 consecutive patients with proven stage IV CRC from
      the year 1995 to 2001. Variables were tested for their relationship to survival
      in univariate analyses with the Kaplan-Meier method and the log rank test.
      Factors that showed a significant impact were included in a Cox proportional
      hazards model. The tests were repeated for 107 patients who had no symptoms from
      their primary tumor. RESULTS: Overall there were six independent variables with a
      relationship to survival: performance status, ASA-class, CEA level, metastatic
      load, extent of primary tumor, and chemotherapy. In the asymptomatic patients we
      investigated 13 factors, 3 of which proved to be independent predictors of
      survival: performance status, CEA level, and chemotherapy. Resection of primary
      tumor was only predictive of survival if in-hospital mortality was excluded.
      CONCLUSION: Resection of the tumor, if possible, is doubtless the best option for
      stage IV CRC patients with severe symptoms caused by their primary tumor. In
      asymptomatic patients, chemotherapy is preferable to surgery.

PMID- 15726624
TI  - Flexibility of metal binding sites in proteins on a database scale.
AB  - Protein metal binding sites in the pre-bound (apo) state, and their
      rearrangements upon metal binding were not analyzed previously at a database
      scale. Such a study may provide valuable information for metal binding site
      prediction and design. A high resolution, nonredundant dataset of 210 metal
      binding sites was created, containing all available representatives of apo-holo
      pairs for the most populated metals in the PDB. More than 40% of the sites
      underwent rearrangements upon metal binding. In 30 cases rearrangements involved
      the backbone. The tendency for side-chain rearrangement inversely correlates with
      the number of first-shell residues. Analysis of side-chain reorientations as a
      result of metal binding showed that in 95% of the rigid-backbone binding sites at
      most one side chain moved. Thus, in general, part of the first coordination shell
      is already in place in the pre-bound form. The frequencies of side-chain
      reorientation directly correlated with metal ligand flexibility and solvent
      accessibility in the apo state.

PMID- 15726623
TI  - Survival and intra-hepatic recurrences after laparoscopic radiofrequency of
      hepatocellular carcinoma in patients with liver cirrhosis.
AB  - BACKGROUND: The optimal treatment for hepatocellular carcinoma (HCC) is surgical
      resection. However, only a small percentage of patients are operative candidates.
      Percutaneous radiofrequency interstitial thermal ablation proved to be effective,
      too. Our objective was to assess a novel operative combination of laparoscopic
      ultrasound (LUS) with laparoscopic radiofrequency (LRF) in the treatment of HCC
      not amenable to liver resection. METHODS: One hundred and four patients with HCC
      in liver cirrhosis were submitted to laparoscopic LRF. A LRF was indicated in
      patients not amenable to liver resection that had at least one of the following
      criteria: (a) severe impairment of the coagulation tests; (b) large tumors (but
      <5 cm) or multiple lesions requiring repeated punctures; (c) superficial lesions
      adjacent to visceral structures; (d) deep-sited lesions with a very difficult or
      impossible percutaneous approach; (e) short-term recurrence of HCC following
      percutaneous loco-regional therapies. RESULTS: The LRF procedure was completed in
      102 out of 104 patients (98% feasibility rate). LUS identified 26 new malignant
      lesions (25%) undetected by pre-operative imaging. There was no operative
      mortality. Seventy-six patients had no complication (73%). At 1-month computed
      tomography (CT) evaluation, a complete response with a 100% necrosis was achieved
      in 88 out of 101 patients (87%). During the follow-up (mean follow-up: 22.5 +/-
      15.9 months), 55 patients (54%) developed new malignant nodules (42% of these
      recurrences were localized in the same segment of the HCC treated). CONCLUSIONS:
      LRF of HCC proved to be a safe and effective technique at least in the short and
      mid-term: in fact it permits to treat lesions not treatable with the per
      cutaneous approach, to detect 25% of new HCC nodules and it has a low morbidity
      rate.

PMID- 15726625
TI  - In vitro drug release studies of 2-hydroxyethyl acrylate or 2-hydroxypropyl
      methacrylate-4-{(1E,4E)-5-[4-(acryloyloxy)phenyl]-3-oxopenta-1,4-dienyl}phenyl
      acrylate copolymer beads.
AB  - 4-{(1E,4E)-5-[4-(Acryloyloxy)phenyl]-3-oxopenta-1,4-dienyl}phenyl acrylate (APPA)
      was synthesized by reacting (1E,4E)-1,5-bis(4-hydroxyphenyl)penta-1,4-dien-3-one
      (HPD) and acryloyl chloride using triethylamine as a base. 2',4-Dichloro-5'
      fluoro-1-ene-2-(4-hydroxyphenyl)phenone (EHP) (Arun A, Reddy BSR, Rajkumar M.
      Polymeric drug for antimicrobial activity studies: Synthesis and
      characterization. J Bioact Compat Polym 2003;18:219) was used for the controlled
      release studies. Two types of porous hydrogels were prepared by copolymerizing 2
      hydroxyethyl acrylate (HEA) or 2-hydroxypropyl methacrylate (HPMA) with APPA (as
      a crosslinker) by employing the suspension polymerization technique. The
      morphology of the hydrogels were characterized by the optical microscopy (OM) and
      scanning electron microscopy (SEM). Different variations were employed in the
      preparation of hydrogels to study the effect of crosslinker percentage and drug
      the loading percentage. Totally 18 types of hydrogels were prepared. The drug
      releasing pattern was monitored over a period of 4 weeks using the UV
      spectroscopic technique by measuring the absorptions at 330.5 nm. In vitro
      release experiments were carried out at pH 7.4 and pH 9.2. In total, 36 releasing
      experiments were conducted. The results showed that the controlled release of the
      drug was dependent on the monomer (HEA or HPMA), crosslinker percentage (CLP),
      drug-loading percentage (DLP), and pH. The release rate was higher for HEA-based
      hydrogels when compared with HPMA-based hydrogels in all compositions. The
      release rate was noticeably higher in pH 9.2 than pH 7.4.

PMID- 15726626
TI  - Cloning of two rat PDIP1 related genes and their interactions with proliferating
      cell nuclear antigen.
AB  - Human polymerase delta-interacting protein 1 (PDIP1) is a tumor necrosis factor
      alpha and interleukin 6 inducible protein that interacts directly with
      proliferating cell nuclear antigen (PCNA) and the small subunit (p50) of DNA
      polymerase delta. PDIP1 binds PCNA and p50 simultaneously and stimulates
      polymerase delta activity in vitro in the presence, but not the absence, of PCNA.
      It has been suggested that PDIP1 provides a link between cytokine activation and
      DNA replication in eukaryotes. Here these authors report the cloning of two rat
      genes homologous to human PDIP1, termed rat PDIP1 and rat tumor necrosis factor
      induced protein 1 (TNFAIP1). The rat PDIP1 is mapped to chromosome 1q36 cM
      region, spans approximately 18.7 kb, and is organized into six exons. The rat
      TNFAIP1 gene is mapped to chromosome 10q25 cM, spans approximately 12.9 kb, and
      is composed of seven exons. The deduced proteins of rat PDIP1 and rat TNFAIP1
      share 63.1% sequence identity with each other and are highly conserved in the
      majority of the middle portion of the two proteins, which encode a BTB/POZ domain
      at the N-terminus and a PCNA binding motif (QTKV-EFP) at the C-terminus,
      respectively. The BTB / POZ domain and the PCNA binding motif are highly
      conserved during the evolution. Both rat PDIP1 and rat TNFAIP1 were demonstrated
      to interact with PCNA via BIAcore, GST pull-down, and co-immunoprecipitation
      assays. Like the human PDIP1, both rat PDIP1 and rat TNFAIP1 stimulate polymerase
      delta activity in vitro in a PCNA-dependent way.

PMID- 15726627
TI  - Solution structure of a tobacco lipid transfer protein exhibiting new biophysical
      and biological features.
AB  - Plant lipid transfer proteins are small soluble extracellular proteins that are
      able to bind and transfer a variety of lipids in vitro. Recently, it has been
      proposed that lipid transfer proteins may play a key role in plant defence
      mechanisms, especially during the induction of systemic acquired resistance.
      However, very little is known about the proteins expressed in developing plants
      and tissues, since almost all the biophysical and structural data available to
      date on lipid transfer proteins originate from proteins present in storage
      tissues of monocot cereal seeds. In this paper, we report the structural and
      functional characteristics of a lipid transfer protein (named LTP1_1)
      constitutively expressed in young aerial organs of Nicotiana tabacum (common
      tobacco). The unlabelled and uniformly labelled proteins were produced in the
      yeast Pichia pastoris, and we determined the three-dimensional (3D) structure of
      LTP1_1 using nuclear magnetic resonance (NMR) spectroscopy and molecular modeling
      techniques. The global fold of LTP1_1 is very close to the previously published
      structures of LTP1 extracted from cereal seeds, including an internal cavity.
      However, the chemical shift variations of several NMR signals upon lipid binding
      show that tobacco LTP1_1 is able to bind only one
      LysoMyristoylPhosphatidylCholine (LMPC), while wheat and maize LTPs can bind
      either one or two. Titration experiments using intrinsic tyrosine fluorescence
      confirm this result not only with LMPC but also with two fatty acids. These
      differences can be explained by the presence in tobacco LTP1_1 of a hydrophobic
      cluster closing the second possible access to the protein cavity. This result
      suggests that LTP1 lipid binding properties could be modulated by subtle changes
      in a conserved global structure. The biological significance of this finding is
      discussed in the light of the signalling properties of the tobacco LTP1_1
      jasmonate complex described elsewhere.

PMID- 15726628
TI  - Calcium currents correlate with oocyte maturation during the reproductive cycle
      in Octopus vulgaris.
AB  - Using the whole-cell voltage clamp technique, we have studied the Ca2+ currents
      and the steady-state conductance during different oocyte growth stages and during
      the reproductive cycle of the female of Octopus vulgaris. Evidence is presented
      that L-type Ca2+ currents are high in small pre-vitellogenic oocytes (80-150
      microm diameter) and significantly lower in early vitellogenic oocytes (180-300
      microm diameter). Similarly, a significant decrease of the steady-state
      conductance occurred from the pre to early- vitellogenic oocytes. Octopus oocytes
      showed larger Ca2+ currents in the reproductive rather than non-reproductive
      periods. These data indicates that ion and L-type Ca2+ currents play a role in
      oocyte growth and cytoplasmic maturation, and possibly in preparing the plasma
      membrane to the interaction with the spermatozoon. By using fluorescent
      microscopy, we show that oocytes from 80 to 400 microm diameter have the large
      germinal vesicle characteristic of the immature oocytes. In subsequent stages of
      growth (up to 1000 microm diameter) the nucleus is no more visible and the
      metaphase spindle appears. These data demonstrate that Octopus vulgaris oocytes
      are arrested in the first meiotic prophase up to the early-vitellogenic stage and
      resume meiosis at this stage up to a second block presumably in metaphase I. We
      discuss a possible role for progesterone as the hormonal stimulus for the first
      prophase-metaphase meiotic transition.

PMID- 15726629
TI  - Response of hepatic antioxidant system to exercise training in aging female rat.
AB  - This study was undertaken to investigate the effect of exercise training on aging
      in the hepatic oxidative status and antioxidant defense of female albino rat. Two
      age groups of 3 months and 12 months old Wistar strain female albino rats were
      given chronic exercise training for a period of 12 weeks. The antioxidant enzyme
      assays were carried out by the standard methods. Lower (P<0.01) activities of the
      antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and
      glutathione reductase (GR) by 21%, 44% and 63% respectively was observed in the
      older rats when compared to younger rats. Also, glutathione (GSH) levels were 42%
      lower (P<0.01) in older than younger animals. Exercise training to the 12 months
      aged rats significantly (P<0.01) elevated these antioxidant enzyme activities and
      GSH content, when compared to older control rats. These levels are almost equal
      to the values observed in the younger control rats. The levels of lipid
      peroxidation end product, malondialdehyde (MDA) the major indicator of oxidative
      stress, was found to increase with age (11%) and exercise training caused further
      elevation (28% of control). The present findings imply that the reactive oxygen
      species that are generated due to aging process were detoxified by the exercise
      induced antioxidant system in the liver tissue. These findings are also in
      agreement with similar changes in male animals, which clearly envisage no gender
      difference in the amelioration of the antioxidant enzyme system in older age due
      to exercise. In conclusion, it can be stated that twelve weeks treadmill exercise
      training has beneficial effect in improving antioxidant defense capacity by
      augmenting SOD, CAT and GR activities and GSH levels of older rats, thereby
      preventing oxidative damage to the liver tissue.

PMID- 15726630
TI  - Phagocytic amoebocyte sub populations in the perivisceral coelom of the sea
      urchin Lytechinus variegatus (Lamarck, 1816).
AB  - The echinoderms are deuterostomic animals with a nonspecific immune system
      similar to that of vertebrates. Among coelomocytes, phagocytic amoebocytes have a
      key role in the nonspecific immune response in sea urchin, being responsible for
      microorganisms elimination through phagocytosis and also for humoral secretions
      of a wide spectrum. Sub-populations of phagocytic amoebocytes (PA) have been
      previously described and two distinct sub populations in the oral (OR) and aboral
      (AB) regions of the perivisceral coelom of L.variegatus in the present study were
      found. In the OR there is a higher number of PA with higher phagocytic capacity
      after 30 minutes of incubation with yeast and higher percentage of intranuclear
      iron crystalloids. The germicide capacity under the fluorescence technique did
      not show any difference. SDS-PAGE analysis showed different protein patterns
      between coelomocytes of OR and AB. Gravitational force had no effect in PA
      distribution and no physical barrier was found in the perivisceral coelom. The
      other coelomocyte (vibratile cells, red spherulocytes and white spherulocytes)
      populations were not different in OR compared with AB in their distribution. Some
      aspects of the possible causes of the differences found for PA are discussed in
      the paper.

PMID- 15726631
TI  - Adenohypophysis regulates cell proliferation in the gonads of the developing
      chick embryo.
AB  - The aim of the present study was to evaluate the effect of hypophysectomy on cell
      proliferation in the left ovary and the left testis of 8- to 14-day-old chick
      embryos. Hypophysectomy was performed by the partial decapitation technique. At
      44-46 h of incubation, chick embryo heads were sectioned at the mesencephalic
      level and the prosencephalic region removed. Embryos were further incubated until
      8-14 days of development. Cell division was evaluated by bromodeoxyuridine (BrdU)
      incorporation and by counting the total number of somatic and germ cells in the
      gonads. The ovary displayed an exponential increase in the number of somatic and
      germ cells and a higher rate of BrdU incorporation compared to the testis. BrdU
      incorporation was reduced in the ovary of hypophysectomized embryos at 9-14 days
      of incubation, while in the testis, the reduction was significant at 14 days of
      development. Changes in the total number of somatic and germ cells further
      suggest that the absence of hypophysis affects the growth of the ovary earlier
      than the growth of the testis. Reduction in the number of somatic and germ cells
      after hypophysectomy in the ovary was reversed by a hypophyseal graft on the
      chorioallantoic membrane. The adenohypophysis regulates, probably through
      gonadotropic hormones, proliferation of somatic and germ cells in the gonads
      during chick embryo development.

PMID- 15726632
TI  - Catecholaminergic and cholinergic regulation of swimming motility development in
      free embryos of Cichlasoma Nigrofasciatum.
AB  - The divergence of progeny from the same spawners of Cichlasoma nigrofasciatum
      into two groups by duration of embryogenesis and the level of motor activity was
      studied close to the end of the embryonic period. Free embryos were also studied.
      During the study, eggs were treated with agents, modifying the activity of
      catecholaminergic and cholinergic systems. 3-Hydroxytyramine and L-Tyrosine were
      found to exert a weak influence on embryonic motility. After hatching, these
      substances modify swimming performance of free embryos, approximating movements
      of fish at later stages. 6-Hydroxydopamine and, still more, alpha-Bungarotoxin,
      decrease embryonic motility and postpone the hatching. The influence of these
      substances on the development of embryo motility increases during early
      ontogenesis, as indicated by decreased concentration of the substance, necessary
      for adequate reaction. Neither L-Tyrosine nor 6-Hydroxydopamine influenced the
      divergence of the progeny into two groups. Injection of the perivitelline fluid
      with high concentration of hatching enzyme from pre-hatching embryos into the
      perivitelline space of earlier embryos was found to induce the appearance of
      rotation movements, typical for more advanced embryos. Changes of correlation
      between the miogenic and neurogenic motor activity during early development of
      fish are discussed.

PMID- 15726633
TI  - Time-related interdependence between low-frequency cortical electrical activity
      and respiratory activity in lizard, Gallotia galloti.
AB  - Electroencephalograms of medial cortex and electromyograms of intercostal muscles
      (EMG-icm) were simultaneously recorded in the lizard, Gallotia galloti, during
      two daily time periods (at daytime, DTP: 1200-1600 h; by night, NTP: 0000-0400
      h), to investigate whether a relationship exists between the respiratory and
      cortical electrical activity of reptiles, and, if so, how this relationship
      changes during the night rest period. Testing was carried out by studying
      interdependence between cortical electrical and respiratory activities, by means
      of linear and nonlinear signal analysis techniques. Both physiological activities
      were evaluated through simultaneous power signals, derived from the power of the
      low-frequency band of the electroencephalogram (pEEG-LF), and from the power of
      the EMG-icm (pEMG-icm), respectively. During both DTP and NTP, there was a
      significant coherence between both signals in the main frequency band of pEMG
      icm. During both DTP and NTP, the nonlinear index N measured significant linear
      asymmetric interdependence between pEEG-LF and pEMG-icm. The N value obtained
      between pEEG-LF vs. pEMG-icm was greater than the one between pEMG-icm vs. pEEG
      LF. This means that the system that generates the pEEG-LF is more complex than
      the one that generates the pEMG-icm, and suggests that the temporal variability
      of power in the low-frequency cortical electrical activity is driven by the power
      of the respiratory activity.

PMID- 15726634
TI  - Solution structure of APETx1 from the sea anemone Anthopleura elegantissima: a
      new fold for an HERG toxin.
AB  - APETx1 is a 42-amino acid toxin purified from the venom of the sea anemone
      Anthopleura elegantissima. This cysteine-rich peptide possesses three disulfide
      bridges (C4-C37, C6-C30, and C20-C38). Its pharmacological target is the Ether-a
      gogo potassium channel. We herein determine the solution structure of APETx1 by
      use of conventional two-dimensional 1H-NMR techniques followed by torsion angle
      dynamics and refinement protocols. The calculated structure of APETx1 belongs to
      the disulfide-rich all-beta structural family, in which a three-stranded anti
      parallel beta-sheet is the only secondary structure. APETx1 is the first Ether-a
      gogo effector discovered to fold in this way. We therefore compare the structure
      of APETx1 to those of the two other known effectors of the Ether-a-gogo potassium
      channel, CnErg1 and BeKm-1, and analyze the topological disposition of key
      functional residues proposed by analysis of the electrostatic anisotropy. The
      interacting surface is made of a patch of aromatic residues (Y5, Y32, and F33)
      together with two basic residues (K8 and K18) at the periphery of the surface. We
      pinpoint the absence of the central lysine present in the functional surface of
      the two other Ether-a-gogo effectors.

PMID- 15726635
TI  - Testosterone and estradiol concentrations in serum, velvet skin, and growing
      antler bone of male white-tailed deer.
AB  - The growth and mineralization of antlers correlate with the seasonal variation of
      serum androgens. Whereas seasonal levels of testosterone (T) in plasma are well
      established, steroid concentrations have not yet been determined in the tissues
      of growing antlers. Therefore, RIA was used to determine T and 17beta estradiol
      (E2) in serum, and three areas (tip, middle, and base) of the antler bone and the
      antler skin, called velvet. Blood and antler tissues of white-tailed deer
      (Odocoileus virginianus) were collected from May to August. The difference
      between levels of T and E2 among the sites was calculated using the square root
      transformation followed by a mixed model analysis with individual deer and an
      interaction of individual and year (individual(*)year) as a random factor.
      Concentrations of T in serum (799+/-82 pg/ml) were higher than T values in the
      velvet (589+/-58 pg/ml, P<0.01) and in the antler bone (538+/-58 pg/ml, P<0.001).
      Estradiol concentrations differed among antler tissues and serum (P<0.001) and
      between years (P<0.01). Estradiol concentrations in serum (25+/-25 pg/ml) were
      consistently lower than those in antler bone (208+/-11 pg/ml, P<0.001) and velvet
      (150+/-12 pg/ml, P<0.001). The E2:T ratio in serum was 1:10-60. The same ratio
      for the antler bone was only 1:2-3 and for the velvet 1:3.5. It is concluded that
      higher T and lower E2 concentrations found in plasma, as compared to antler bone
      or antler velvet, may indicate a partial metabolism of systemic androgens into
      estrogens xin the tissues of growing antlers.

PMID- 15726636
TI  - Functional analysis of CYP2D6.31 variant: homology modeling suggests possible
      disruption of redox partner interaction by Arg440His substitution.
AB  - Cytochrome P450 2D6 (CYP2D6) is an important human drug-metabolizing enzyme that
      exhibits a marked genetic polymorphism. Numerous CYP2D6 alleles have been
      characterized at a functional level, although the consequences for expression
      and/or catalytic activity of a substantial number of rare variants remain to be
      investigated. One such allele, CYP2D6*31, is characterized by mutations encoding
      three amino acid substitutions: Arg296Cys, Arg440His and Ser486Thr. The
      identification of this allele in an individual with an apparent in vivo poor
      metabolizer phenotype prompted us to analyze the functional consequence of these
      substitutions on enzyme activity using yeast as a heterologous expression system.
      We demonstrated that the Arg440His substitution, alone or in combination with
      Arg296Cys and/or Ser486Thr, altered the respective kinetic parameters [Km
      (microM) and kcat (min(-1))] of debrisoquine 4-hydroxylation (wild-type, 25;
      0.92; variants, 43-68; 0.05-0.11) and dextromethorphan O-demethylation (wild
      type, 1; 4.72; variants, 12-23; 0.64-1.43), such that their specificity constants
      (kcat/Km) were decreased by more than 95% compared to those observed with the
      wild-type enzyme. The rates of oxidation of rac-metoprolol at single substrate
      concentrations of 40 and 400 microM were also markedly decreased by approximately
      90% with each CYP2D6 variant containing the Arg440His substitution. These in
      vitro data confirm that the CYP2D6*31 allele encodes an enzyme with a severely
      impaired but residual catalytic activity and, furthermore, that the Arg440His
      exchange alone is the inactivating mutation. A homology model of CYP2D6 based on
      the crystal structure of rabbit CYP2C5 locates Arg440 on the proximal surface of
      the protein. Docking the structure of the FMN domain of human cytochrome P450
      reductase to the CYP2D6 model suggests that Arg440 is a key member of a cluster
      of basic amino acid residues important for reductase binding.

PMID- 15726637
TI  - Solution structure of two insect-specific spider toxins and their pharmacological
      interaction with the insect voltage-gated Na+ channel.
AB  - Delta-paluIT1 and delta-paluIT2 are toxins purified from the venom of the spider
      Paracoelotes luctuosus. Similar in sequence to mu-agatoxins from Agelenopsis
      aperta, their pharmacological target is the voltage-gated insect sodium channel,
      of which they alter the inactivation properties in a way similar to alpha
      scorpion toxins, but they bind on site 4 in a way similar to beta-scorpion
      toxins. We determined the solution structure of the two toxins by use of two
      dimensional nuclear magnetic resonance (NMR) techniques followed by distance
      geometry and molecular dynamics. The structures of delta-paluIT1 and delta
      paluIT2 belong to the inhibitory cystine knot structural family, i.e. a compact
      disulfide-bonded core from which four loops emerge. Delta-paluIT1 and delta
      paluIT2 contain respectively two- and three-stranded anti-parallel beta-sheets as
      unique secondary structure. We compare the structure and the electrostatic
      anisotropy of those peptides to other sodium and calcium channel toxins, analyze
      the topological juxtaposition of key functional residues, and conclude that the
      recognition of insect voltage-gated sodium channels by these toxins involves the
      beta-sheet, in addition to loops I and IV. Besides the position of culprit
      residues on the molecular surface, difference in dipolar moment orientation is
      another determinant of receptor binding and biological activity differences. We
      also demonstrate by electrophysiological experiments on the cloned insect voltage
      gated sodium channel, para, heterologuously co-expressed with the tipE subunit in
      Xenopus laevis oocytes, that delta-paluIT1 and delta-paluIT2 procure an increase
      of Na+ current. delta-PaluIT1-OH seems to have less effect when the same
      concentrations are used.

PMID- 15726638
TI  - Cation-pi interactions in protein-protein interfaces.
AB  - Arginine is an abundant residue in protein-protein interfaces. The importance of
      this residue relates to the versatility of its side chain in intermolecular
      interactions. Different classes of protein-protein interfaces were surveyed for
      cation-pi interactions. Approximately half of the protein complexes and one-third
      of the homodimers analyzed were found to contain at least one intermolecular
      cation-pi pair. Interactions between arginine and tyrosine were found to be the
      most abundant. The electrostatic interaction energy was calculated to be
      approximately 3 kcal/mol, on average. A distance-based search of
      guanidinium:aromatic interactions was also performed using the Macromolecular
      Structure Database (MSD). This search revealed that half of the
      guanidinium:aromatic pairs pack in a coplanar manner. Furthermore, it was found
      that the cationic group of the cation-pi pair is frequently involved in
      intermolecular hydrogen bonds. In this manner the arginine side chain can
      participate in multiple interactions, providing a mechanism for inter-protein
      specificity. Thus, the cation-pi interaction is established as an important
      contributor to protein-protein interfaces.

PMID- 15726639
TI  - Inhibition of alcohol dehydrogenase after 2-propanol exposure in different
      geographic races of Drosophila mojavensis: lack of evidence for selection at the
      Adh-2 locus.
AB  - High frequencies of the fast allele of alcohol dehydrogenase-2 (Adh-2F) are found
      in populations of Drosophila mojavensis that inhabit the Baja California
      peninsula (race BII) whereas the slow allele (Adh-2S) predominates at most other
      localities within the species' geographic range. Race BII flies utilize necrotic
      tissue of pitaya agria cactus (Stenocereus gummosus) which contains high levels
      of 2-propanol, whereas flies from most other localities utilize different cactus
      hosts in which 2-propanol levels are low. To test if 2-propanol acts as a
      selective force on Adh-2 genotype, or whether some other yet undetermined genetic
      factor is responsible, mature males of D. mojavensis lines derived from the Grand
      Canyon (race A) and Santa Catalina Island (race C), each with individuals
      homozygous for Adh-2F and Adh-2S, were exposed to 2-propanol for 24 h and ADH-2
      specific activity was then determined on each genotype. Flies from five other
      localities homozygous for either the fast or slow allele also were examined.
      Results for all reported races of D. mojavensis were obtained. 2-propanol
      exposure inhibited ADH-2 specific activity in both genotypes from all localities,
      but inhibition was significantly less in two populations of race BII flies
      homozygous for Adh-2F. When F/F and S/S genotypes in flies from the same locality
      were compared, both genotypes showed high 2-propanol inhibition that was not
      statistically different, indicating that the F/F genotype alone does not provide
      a benefit against the inhibitory effects of 2-propanol. ADH-1 activity in female
      ovaries was inhibited less by 2-propanol than ADH-2. These results do not support
      the hypothesis that 2-propanol acts as a selective factor favoring the Adh-2F
      allele.

PMID- 15726641
TI  - Metalloproteinase inhibitor TIMP-1 affects hepatocyte cell cycle via HGF
      activation in murine liver regeneration.
AB  - Liver regeneration depends on timely restoration of cellular mass while
      orchestrating structural matrix remodeling. Matrix metalloproteinases (MMPs) and
      their endogenous inhibitors (TIMPs) are known to regulate the extracellular
      matrix (ECM) turnover and, more recently, the processing of growth factors and
      cytokines. We have previously demonstrated that TIMP-1 inhibits preneoplastic
      hepatocyte proliferation by attenuating growth factor bioavailability. In the
      present study, we examined the role of TIMP-1 in de novo hepatocyte cell division
      during liver regeneration. Comprehensive real-time reverse-transcriptase
      polymerase chain reaction analyses of regenerating livers revealed significant
      inductions in the messenger RNA of TIMP-1, TIMP-3, TIMP-4, MMP-2, MMP-9, MMP-13,
      MMP-14, and MMP-24, while MMP-15 expression was significantly reduced. Induction
      of TIMP-1 occurred during the peak of hepatocyte DNA synthesis. Studies using
      genetically altered mice revealed that TIMP-1 loss of function accelerated
      hepatocyte cell cycle progression. This finding was demonstrated by earlier
      expression of cyclin D1, proliferating cell nuclear antigen, and phosphorylated
      histone H3, which mark the G(1)-S, S, and M phase, respectively. Conversely, TIMP
      1 gain of function delayed cell cycle progression. MMP activity was increased in
      the absence of Timp-1. Examination of hepatocyte growth factor (HGF), and its
      receptor Met, both of which provide a mitogenic signal for hepatocyte division,
      showed increased HGF activity in Timp-1(-/-)-regenerating livers. HGF is released
      from the ECM and is proteolytically processed to its active form. Active HGF was
      elevated in Timp-1(-/-) mice, leading to increased immunostaining of
      phosphorylated Met as well as activation of a downstream effector, p38. In
      conclusion, TIMP-1 is a novel negative regulator of HGF activity during liver
      regeneration.

PMID- 15726642
TI  - Fatigue of cholestasis and the serotoninergic neurotransmitter system in the rat.
AB  - Fatigue associated with cholestasis may impair health-related quality of life.
      The pathogenesis of this symptom is largely unknown, but it has been suggested
      that central serotoninergic neurotransmission may be implicated and that
      serotonin 1A receptor agonists may yield improvement. The aim of this study was
      to study the central serotoninergic system, specifically the serotonin (5-HT)(1A)
      receptor-mediated pathway of serotoninergic neurotransmission, in a bile duct
      resection rat model of cholestasis. Fatigue was assessed in the forced swim test
      in sham and bile duct-resected rats. The serotonin behavioral syndrome, which
      includes hyperlocomotion, was assessed in both groups of rats after escalating
      doses of the 5-HT(1A) receptor agonist 8-hydroxy(di-n-propylamine)tetralin (8-OH
      DPAT). 5-HT(1A) and 5-HT(2) receptor densities were explored in four brain
      regions using a receptor-binding assay. Extracellular 5-HT and 5
      hydroxyindoleacetic acid were measured via in vivo brain dialysis. Bile duct
      resected rats spent more time floating in the forced swim test, and 8-OH DPAT
      decreased floating time in cholestatic rats (P < .01). Dose-response curves
      created with 8-OH DPAT for the serotonin behavioral syndrome were similar in bile
      duct-resected and sham-operated rats. 5-HT(1A) and 5-HT(2) receptor densities in
      most brain regions and extracellular serotonin levels were similar in both groups
      of rats. In conclusion, 5-HT(1A) receptor agonist-induced amelioration of fatigue
      in cholestatic rats may be nonspecific and not linked to reversal of the
      pathophysiology of fatigue associated with cholestasis; however, these data do
      not exclude a potential role of the central serotoninergic system in the
      evolution of fatigue.

PMID- 15726643
TI  - Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces
      nodular proliferation of hepatocytes.
AB  - Naturally occurring mutants with a deletion in the pre-S2 region of the large
      surface protein (Delta S2-LHBs) are prevalent in serum and livers of patients
      with chronic hepatitis B virus (HBV) infection associated with cirrhosis. The
      Delta S2-LHBs protein is retained in the endoplasmic reticulum (ER) and may
      induce ER stress. One interesting observation is the consistently clustered
      distribution of hepatocytes expressing Delta S2-LHBs. In this study,
      complementary DNA microarray analysis identified cyclin A and several groups of
      genes as being significantly upregulated by Delta S2-LHBs in the HuH-7 cell line.
      This observation was confirmed in liver tissues. The induction of cyclin A
      expression may occur via the specific transactivator function of Delta S2-LHBs
      independent of ER stress. In the presence of Delta S2-LHBs, hepatocytes sustained
      cyclin A expression and cell cycle progression under ER stress and displayed
      increased BrdU incorporation with multinuclear formation. Furthermore, Delta S2
      LHBs could enhance anchorage-independent cell growth in a nontransformed human
      hepatocyte line and induced nodular proliferation of hepatocytes in transgenic
      mice. In conclusion, these in vitro and in vivo data support a role for Delta S2
      LHBs in the hepatocyte hyperplasia and a likely role in the process of HBV
      related tumorigenesis.

PMID- 15726644
TI  - Dual role of orphan nuclear receptor pregnane X receptor in bilirubin
      detoxification in mice.
AB  - The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are
      implicated in xenobiotic and endobiotic detoxification, including the clearance
      of toxic bilirubin. Previous studies have suggested both overlapping and
      preferential regulation of target genes by these receptors, but the mechanism of
      cross-talk remains elusive. Here we reveal a dual role of PXR in bilirubin
      detoxification in that both the loss and activation of PXR led to protection from
      hyperbilirubinemia induced by bilirubin infusion or hemolysis. The increased
      bilirubin clearance in PXR-null mice was associated with selective upregulation
      of detoxifying enzymes and transporters, and the pattern of regulation is
      remarkably similar to that of transgenic mice expressing the activated CAR.
      Interestingly, the increased bilirubin clearance and associated gene regulation
      were absent in the CAR-null or double-knockout mice. In cell cultures, ligand
      free PXR specifically suppressed the ability of CAR to induce the multidrug
      resistance associated protein 2 (MRP2), a bilirubin-detoxifying transporter. This
      suppression was, at least in part, the result of the disruption of ligand
      independent recruitment of coactivator by CAR. In conclusion, PXR plays both
      positive and negative roles in regulating bilirubin homeostasis, and this
      provides a novel mechanism that may govern receptor cross-talk and the hierarchy
      of xenobiotic and endobiotic regulation. PXR is a potential therapeutic target
      for clinical treatment of jaundice. (HEPATOLOGY 2005;41:497-505.).

PMID- 15726645
TI  - Magnetic fluid hyperthermia (MFH)reduces prostate cancer growth in the orthotopic
      Dunning R3327 rat model.
AB  - BACKGROUND: Magnetic fluid hyperthermia (MFH) is a new technique for interstitial
      hyperthermia or thermoablation based on AC magnetic field-induced excitation of
      biocompatible superparamagnetic nanoparticles. Preliminary studies in the Dunning
      tumor model of prostate cancer have demonstrated the feasibility of MFH in vivo.
      To confirm these results and evaluate the potential of MFH as a minimally
      invasive treatment of prostate cancer we carried out a systematic analysis of the
      effects of MFH in the orthotopic Dunning R3327 tumor model of the rat. METHODS:
      Orthotopic tumors were induced by implantation of MatLyLu-cells into the
      prostates of 48 male Copenhagen rats. Animals were randomly allocated to 4 groups
      of 12 rats each, including controls. Treatment animals received two MFH
      treatments following a single intratumoral injection of a magnetic fluid.
      Treatments were carried out on days 10 and 12 after tumor induction using an AC
      magnetic field applicator system operating at a frequency of 100 kHz and a
      variable field strength (0--18 kA/m). On day 20, animals were sacrificed and
      tumor weights in the treatment and control groups were compared. In addition,
      tumor growth curves were generated and histological examinations and iron
      measurements in selected organs were carried out. RESULTS: Maximum intratumoral
      temperatures of over 70 degrees C could be obtained with MFH at an AC magnetic
      field strength of 18 kA/m. At a constant field strength of 12.6 kA/m, mean
      maximal and minimal intratumoral temperatures recorded were 54.8 degrees C
      (centrally) and 41.2 degrees C (peripherally). MFH led to an inhibition of tumor
      growth of 44%-51% over controls. Mean iron content in the prostates of treated
      and untreated (injection of magnetic fluids but no AC magnetic field exposure)
      animals was 82.5%, whereas only 5.3% of the injected dose was found in the liver,
      1.0% in the lung, and 0.5% in the spleen. CONCLUSIONS: MFH led to a significant
      growth inhibition in this orthotopic model of the aggressive MatLyLu tumor
      variant. Intratumoral deposition of magnetic fluids was found to be stable,
      allowing for serial MFH treatments without repeated injection. The optimal
      treatment schedules and temperatures for MFH need to be defined in further
      studies.

PMID- 15726646
TI  - SELDI-TOF MS profiling of serum for detection of the progression of chronic
      hepatitis C to hepatocellular carcinoma.
AB  - Proteomic profiling of serum is an emerging technique to identify new biomarkers
      indicative of disease severity and progression. The objective of our study was to
      assess the use of surface-enhanced laser desorption/ionization time-of-flight
      mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers
      for detection of liver disease progression to hepatocellular carcinoma (HCC). A
      cohort of 170 serum samples obtained from subjects in the United States with no
      liver disease (n = 39), liver diseases not associated with cirrhosis (n = 36),
      cirrhosis (n = 38), or HCC (n = 57) were applied to metal affinity protein chips
      for protein profiling by SELDI-TOF MS. Across the four test groups, 38
      differentially expressed proteins were used to generate multiple decision
      classification trees to distinguish the known disease states. Analysis of a
      subset of samples with only hepatitis C virus (HCV)-related disease was
      emphasized. The serum protein profiles of control patients were readily
      distinguished from each HCV-associated disease state. Two-way comparisons of
      chronic hepatitis C, HCV cirrhosis, or HCV-HCC versus healthy had a
      sensitivity/specificity range of 74% to 95%. For distinguishing chronic HCV from
      HCV-HCC, a sensitivity of 61% and a specificity of 76% were obtained. However,
      when the values of known serum markers alpha fetoprotein, des-gamma
      carboxyprothrombin, and GP73 were combined with the SELDI peak values, the
      sensitivity and specifity improved to 75% and 92%, respectively. In conclusion,
      SELDI-TOF MS serum profiling is able to distinguish HCC from liver disease before
      cirrhosis as well as cirrhosis, especially in patients with HCV infection
      compared with other etiologies.

PMID- 15726647
TI  - Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection.
AB  - Chronic evolution of acute hepatitis C (aHC) occurs in more than 80% of patients
      but can frequently be prevented by early treatment with interferon (IFN)-alpha.
      Plasmacytoid dendritic cells (pDCs) are the major endogenous IFN-alpha producers,
      but their role in aHC is unknown. In this study, frequency, phenotype, and pDC
      function were analyzed in 13 patients with aHC and 32 patients with chronic
      hepatitis C (cHC) compared with 20 healthy controls, 33 sustained responders to
      antiviral treatment, 14 patients with acute hepatitis B (aHB), and 21 patients
      with nonviral inflammatory disease. In aHC, pDCs in the peripheral blood were
      significantly reduced compared with healthy controls (median, 0.1% vs. 0.36%, P <
      .0005) and were inversely correlated to alanine aminotransferase levels (r = 
      0.823; P < .005). Circulating pDCs in aHC were immature, as determined via
      reduced expression of HLA-DR and CCR7, and produced little amounts of IFN-alpha
      (median, 3.5 pg/50,000 peripheral blood mononuclear cells [PBMCs] vs. 498.4
      pg/50,000 PBMCs in healthy controls; P < .0005). Less pronounced changes were
      present in cHC (median, 0.17%, 28.0 pg/50,000 PBMCs IFN-alpha, respectively).
      However, a significantly reduced frequency and IFN-alpha production was also
      found in self-limited aHB (median 0.1%, 8.6 pg/50,000 PBMCs) and in patients with
      nonviral inflammatory disease (median 0.19%, 7.5 pg/50,000 PBMCs). In conclusion,
      in aHC frequency and IFN-alpha-producing capacity of peripheral blood pDCs are
      dramatically reduced and inversely correlated with the degree of liver
      inflammation. In cHC there is incomplete recovery of pDC function, which,
      however, could be solely due to the chronic inflammatory state.

PMID- 15726648
TI  - Aberrant expression of transforming growth factor beta-1 (TGF beta-1) per se does
      not discriminate fibrotic from non-fibrotic chronic myeloproliferative disorders.
AB  - Transforming growth factor beta-1 (TGF beta-1) is a potent inducer of fibrosis
      and has been shown to be essential for the development of bone marrow fibrosis in
      an animal model of idiopathic myelofibrosis (IMF). IMF belongs to the
      Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-)
      CMPD). Megakaryocytes and platelets have been suggested as the major cellular
      source of TGF beta-1 in IMF. The osteoclastogenesis inhibitory factor
      osteoprotegerin (OPG) seems to be regulated by TGF beta-1 and substantial
      involvement of OPG expression in the process of osteosclerosis in IMF has
      recently been suggested. In order to determine TGF beta-1 expression in IMF and
      other Ph(-) CMPD, total bone marrow cells as well as laser-microdissected
      megakaryocytes were quantitatively analysed by real-time RT-PCR. OPG mRNA
      expression in fibrotic IMF was correlated with TGF beta-1 mRNA expression in a
      case-specific manner. Both OPG and TGF beta-1 were detected immunohistochemically
      in order to delineate cellular origin. When total bone marrow cells were
      investigated, TGF beta-1 mRNA expression was increased in some but not all cases
      of IMF (n = 21), with highest values in fibrotic cases. Unexpectedly, increased
      values were also observed in essential thrombocythaemia (ET, n = 11) when
      compared to non-neoplastic haematopoiesis (n = 38). Megakaryocytes isolated by
      laser microdissection displayed elevated TGF beta-1 mRNA levels in most of the
      CMPD samples with no significant differences discernible between fibrotic IMF,
      polycythaemia vera (PV) and ET. TGF beta-1 protein was predominantly expressed by
      the myeloid lineage in Ph(-) CMPD and non-neoplastic haematopoiesis, which,
      however, displayed lower expression. IMF cases with advanced fibrosis
      concomitantly overexpressed TGF beta-1 and OPG. Immunohistochemically, OPG
      expression was found in different stromal cells and a subfraction of
      megakaryocytes. In conclusion, enhanced TGF beta-1 expression occurs in
      megakaryocytes as well as myeloid cells in Ph(-) CMPD. TGF beta-1 may be
      necessary, but is not sufficient, to induce bone marrow fibrosis in IMF because
      non-fibrotic Ph(-) CMPD entities share this feature with IMF and cannot be
      discriminated from each other on the basis of TGF beta-1 expression.

PMID- 15726649
TI  - G to A hypermutation of hepatitis B virus.
AB  - G to A hypermutation of the human immunodeficiency virus type 1 (HIV-1) is
      induced by a deaminase APOBEC3G and is related to host antiviral defense.
      APOBEC3G has also been found to reduce the replication of HIV-1 by an unknown
      mechanism. This enzyme also reduces the production of hepatitis B virus, although
      the mechanism for this action has not been clearly elucidated. The hypermutated
      hepatitis B virus (HBV) is rarely found in usual sequencing analyses. Using
      peptide nucleic acid mediated by polymerase chain reaction clamping, we detected
      the hypermutated HBV DNA in 1 of 8 patients with acute HBV infection and 4 of 10
      with chronic HBV infection. In the latter group, hypermutated genomes were found
      only in eAb-positive patients. As much as 72.5% of G residues were mutated in the
      hypermutated clones. G to A substitutions were predominant in almost all clones
      sequenced compared with other substitutions. G to A mutated viral genomes also
      were found in HepG2-derived cell lines that continuously produced HBV into the
      supernatant. Both alpha and gamma interferon reduced virus production in these
      cell lines, but they did not alter the frequency of the hypermutation.
      Transcripts of APOBEC3G, as well as some other deaminases, were found in these
      cell lines. In conclusion, our results show that part of the minus strand DNA of
      HBV is hypermutated both in vitro (HepG2 cell lines) and in vivo. The role and
      mechanism of hypermutation in reducing HBV replication should be further
      investigated to understand the anti-HBV defense system.

PMID- 15726650
TI  - Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric
      and colon cancer.
AB  - Eight members of the nm23-gene family have been described. The involvement of
      nm23-H1 and nm23-H2 in tumour progression and metastasis, as well as in gene
      regulation and apoptosis, has been shown in numerous studies. Whether nm23-H4, 
      H6, and -H7 play a role in tumours is, however, largely unknown. This study
      describes data on the expression of these three nm23 homologues in human colon
      and gastric cancer by real-time RT-PCR and immunohistochemistry. Increased
      expression of these genes, most strikingly nm23-H4 and -H7, was observed in the
      majority of tumours analysed. No correlation with tumour stage according to the
      TNM classification was found. In contrast, by immunohistochemical analysis, nm23
      H4 and -H6 overexpression correlated with the intestinal tumour type in gastric
      cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins
      was noted in the diffuse type tumour specimens. These findings indicate that nm23
      H6, and particularly nm23-H4 and -H7, may be involved in the development of colon
      and gastric carcinoma, the latter possibly in a type-specific manner. A
      contribution to tumour progression or metastasis could not, however, be proven.
      Elucidation of the specific mechanisms by which the nm23 homologues nm23-H4, -H6,
      and -H7 are involved in tumour development requires further studies.

PMID- 15726651
TI  - Aberrations in the progesterone receptor gene and the risk of recurrent
      endometrial carcinoma.
AB  - A case-control study was performed in order to determine whether expression of
      the progesterone receptor (PR) and/or aberrations of the PR gene contribute to
      the development of recurrent endometrial carcinoma. Primary tumours from 44
      patients with recurrence of stage I endometrial carcinoma (patients) within 3
      years after initial treatment were compared with tumours from 44 matched patients
      who were free of recurrence for a minimum of 3 years (controls). Paraffin wax
      embedded primary tumours (n = 88) and recurrent tumours (n = 32) were analysed
      immunohistochemically for PR expression. A staining index (SI = 0-9) based on the
      staining intensity and the number of stained cells was calculated. DNA extracted
      from paraffin wax-embedded tissues was subjected to PCR-restriction fragment
      length polymorphism analysis (PCR-RFLP) for determination of the PROGINS DNA
      sequence alterations and the +331G/A-promoter polymorphism. Low PR expression (SI
      < 1.0) was observed in 7% of primary tumours derived from controls, 25% of
      primary tumours from patients with recurrence, and 38% of recurrent tumours. The
      expression of PR was significantly lower in primary tumours from patients with
      recurrence (SI = 4.0 +/- 0.5) than in the tumours in the control group (SI = 5.6
      +/- 0.5) (T-test for paired analysis, p < 0.05). The PROGINS and +331G/A-promoter
      polymorphism were not related to age at diagnosis, tumour grade or myometrial
      invasion. The +331G/A-promoter polymorphism was present in 14% of primary tumours
      from patients without recurrence, compared with 17% of patients with recurrence.
      The PROGINS polymorphism was observed in 16% of primary tumours from patients
      without, and in 34% of patients with, recurrence (OR 2.6; 95% CI: 0.9-7.6). Most
      interestingly, patients who carried the PROGINS variant and in whom a PR
      expressing tumour was diagnosed were at significantly enhanced risk of relapse
      (OR 4.7; 95% CI: 1.3-17.1). In conclusion, low PR expression tended to be
      associated with recurrent disease, and PR expression in tumours from patients
      carrying the PROGINS allele was predictive of the risk of recurrence.

PMID- 15726652
TI  - Small ubiquitin-related modifiers: A novel and independent class of autoantigens
      in primary biliary cirrhosis.
AB  - Serum autoantibodies against components of nuclear dots (anti-NDs), namely PML
      and Sp100, are specifically detected in 20% to 30% of patients with primary
      biliary cirrhosis (PBC). Although anti-ND antibodies are nonpathogenic, the
      mechanisms that lead to this unique reactivity are critical to understanding the
      loss of immune tolerance in PBC. Importantly, Sp100 and PML are both covalently
      linked to small ubiquitin-related modifiers (SUMOs). Therefore, we investigated
      whether SUMO proteins are independent autoantigens in PBC and studied 99 PBC sera
      samples for reactivity against NDs, PML, and Sp100, as well as against SUMO-2 and
      SUMO-1 recombinant proteins. Autoantibodies against SUMO-2 and SUMO-1 were found
      in 42% and 15% of anti-ND-positive PBC sera, respectively. Anti-SUMO reactivity
      was not observed in anti-ND-negative sera. Anti-SUMO-2 autoantibodies were found
      in 58% of sera containing autoantibodies against both PML and Sp100 and were
      detected exclusively in sera containing anti-Sp100 autoantibodies. In conclusion,
      SUMO proteins constitute a novel and independent class of autoantigens in PBC.
      Furthermore, we believe our data emphasize the post-translational modification of
      lysine by either lipoylation in the case of AMA or SUMOylation in the case of
      specific anti-ND autoantibodies as the pivotal site for autoantibody generation
      in PBC.

PMID- 15726653
TI  - Risk factors for thrombophilia in extrahepatic portal vein obstruction.
AB  - Scant information exists on the role of thrombophilia in extrahepatic portal vein
      obstruction (EHPVO). We studied 65 patients with EHPVO, 500 with deep vein
      thrombosis (DVT) of the lower limbs, and 700 healthy controls referred for
      thrombophilia screening, including the search for gain-of-function mutations in
      genes encoding coagulation factor V (factor V Leiden) and prothrombin
      (prothrombin G20210A); antithrombin, protein C, and protein S deficiency; and
      hyperhomocysteinemia. At least one abnormality in the thrombophilia screening was
      found in 40% of patients with either EHPVO or lower limb DVT and in 13% of
      controls, for odds ratios of 4.0 (95% CI, 2.3-7.0) and 4.4 (95% CI, 3.3-5.9),
      respectively. Statistically significant associations with EHPVO were observed for
      the prothrombin G20210A mutation (odds ratio, 8.1; 95% CI, 3.8-17.5) and the
      deficiencies of antithrombin, protein C, or protein S taken together (odds ratio,
      4.5; 95% CI, 1.1-18.0). The odds ratio for the prothrombin G20210A was
      approximately twice that for lower limb DVT. Patients with factor V Leiden had an
      odds ratio for EHPVO of 0.8 (95% CI, 0.1-6.4) and for lower limb DVT of 7.5 (95%
      CI, 4.4-13.0). The odds ratio for EHPVO in patients with hyperhomocysteinemia was
      2.0 (95% CI, 0.9-4.9). At variance with lower limb DVT, oral contraceptive use
      was not associated with an increased risk of EHPVO. Myeloproliferative disorders
      were diagnosed in 35% of patients with EHPVO. In conclusion, the risk for EHPVO
      is increased in the presence of thrombophilia resulting from the prothrombin
      G20210A mutation and from the deficiencies of the naturally occurring
      anticoagulant proteins, but not from factor V Leiden.

PMID- 15726654
TI  - Patients with cirrhosis and bare-stent TIPS may have increased risk of
      hepatocellular carcinoma.
AB  - A trend toward a higher incidence of hepatocelullar carcinoma (HCC) in patients
      with cirrhosis treated with bare-stent transjugular intrahepatic portosystemic
      shunt (TIPS) has been observed in previous studies. To assess the influence of
      TIPS as a risk factor for developing HCC, we have compared the incidence of HCC
      in two retrospective cohorts of patients. The TIPS cohort (n = 138) included
      patients with cirrhosis who underwent TIPS placement for the treatment of portal
      hypertension-related complications; the non-TIPS cohort was composed of patients
      admitted at the hospital at the same time of TIPS insertion who were individually
      matched 1:1 according to age, sex, Child-Turcotte-Pugh class, and cause of
      cirrhosis. A stratified Cox model was used to assess risk of HCC development. The
      median time of follow-up was similar in TIPS and non-TIPS cohorts (30.3 [range,
      7.8-119.5] and 31.4 [range, 7.8-110.8] months, respectively). The cumulative
      probability of developing HCC at 1, 3, and 5 years was 3%, 24%, and 34% for the
      TIPS cohort and 1%, 6%, and 25%, for the non-TIPS cohort, respectively (Breslow
      test = 5.23, P = .022). The adjusted hazard ratio was 1.52 (95% confidence
      interval, 1.06-2.19; P = .02). Hepatitis C virus infection and age were
      independent predictors of HCC development in patients without TIPS. In
      conclusion, patients with cirrhosis who are treated with TIPS may have a higher
      incidence of HCC. This observation suggests the need for a strict HCC
      surveillance program for these patients, especially if they are not expected to
      undergo a short- or medium-term liver transplantation.

PMID- 15726655
TI  - The human liver clears both asymmetric and symmetric dimethylarginine.
AB  - Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of
      nitric oxide. The concentration of both dimethylarginines is regulated by urinary
      excretion, although ADMA, but not SDMA, is also subject to degradation by
      dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver
      but also present in the kidney. The exact roles of the human liver and kidney in
      the metabolism of dimethylarginines are currently unknown. Therefore, we aimed to
      investigate renal and hepatic handling of ADMA and SDMA in detail in 24 patients
      undergoing hepatic surgery. To calculate net organ fluxes and fractional
      extraction (FE) rates, blood was collected from an arterial line, the portal
      vein, hepatic vein, and renal vein, and blood flow of the hepatic artery, portal
      vein, and renal vein was determined using Doppler ultrasound techniques. Results
      showed a significant net uptake (median [IQR]) of ADMA in both the liver (9.6
      nmol/min [5.6-13.2]) and the kidney (12.1 nmol/min [1.3-17.1]). SDMA uptake was
      present not only in the kidney (12.7 nmol/min [3.5-25.4]), but also in the liver
      (7.7 nmol/min [2.8-16.4]). FE rates of ADMA for the liver and kidney were 5.0%
      (3.5%-7.4%) and 8.4% (1.3%-13.9%), respectively. For SDMA, hepatic and renal FE
      rates were 3.4% (2.1%-7.5%) and 12.5% (3.6%-16.2%), respectively. In conclusion,
      this study gives a detailed description of the hepatic and renal elimination of
      dimethylarginines and shows that the clearing of SDMA is not only confined to the
      kidney, but the human liver also takes up substantial amounts of SDMA from the
      portal and systemic circulation.

PMID- 15726656
TI  - Associations among clinical, immunological, and viral quasispecies measurements
      in advanced chronic hepatitis C.
AB  - The relationships among host immune and viral factors and the severity of liver
      disease due to hepatitis C virus (HCV) are poorly understood. Previous studies
      have focused on individual components of the immune response to HCV, often in
      relatively small numbers of patients. We measured HCV-specific
      lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and
      neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and
      complexity in a large cohort of subjects with advanced liver fibrosis (Ishak
      stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment
      against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical
      characteristics, including serum alanine aminotransferase (ALT), HCV RNA level,
      HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected
      in 37%, 22%, and 22% of subjects tested, respectively. The only association that
      was statistically significant was higher mean serum ALT values in patients with
      detectable HCV-specific CTL responses (P = .03). In conclusion, immune responses
      to HCV and viral diversity showed little relationship to clinical or histological
      features at a single time point in this selected population of patients with
      advanced chronic hepatitis C for whom prior interferon treatment had failed.

PMID- 15726657
TI  - No relevant effect of ursodeoxycholic acid on cytochrome P450 3A metabolism in
      primary biliary cirrhosis.
AB  - Induction of cytochrome P450 3A (CYP3A) has been suggested as a mechanism of
      action of ursodeoxycholic acid (UDCA) in cholestasis. CYP3A is of key importance
      in human drug metabolism, being involved in presystemic extraction of more than
      50% of all drugs currently available and of various endogenous compounds.
      Therefore, we compared the induction potential of UDCA with that of the
      prototypical inducer rifampicin in a human model study with the CYP3A substrates
      budesonide and cortisol. Twelve patients with early-stage primary biliary
      cirrhosis and eight healthy volunteers were treated with UDCA (15 mg/kg daily)
      for 3 weeks and subsequently with rifampicin (600 mg/d) for 1 week. Extensive
      pharmacokinetic profiling of oral budesonide (3 mg) was performed by
      determination of budesonide and phase I metabolites (6beta-hydroxybudesonide,
      16alpha-hydroxyprednisolone) in plasma and urine at baseline and at the end of
      each treatment. In parallel, urinary 6beta-hydroxycortisol, a validated marker of
      CYP3A induction, was determined. UDCA did not affect biotransformation of
      budesonide and urinary excretion of 6beta-hydroxycortisol either in patients or
      in healthy volunteers. Ratios of areas under plasma concentration-time curves
      (AUC(0-12 h) during UDCA/AUC(0-12 h) before UDCA) of both metabolites were not
      higher than those of budesonide itself. In contrast, administration of rifampicin
      markedly induced CYP3A metabolism, resulting in abolished budesonide plasma
      levels and high urinary excretion of 6beta-hydroxycortisol. Metabolite formation
      was enhanced by rifampicin, but not by UDCA (e.g., AUC(16alpha
      hydroxyprednisolone)/AUC(budesonide) in patients: baseline, 8.6 +/- 3.9; UDCA,
      10.7 +/- 7.1; rifampicin, 527.0 +/- 248.7). In conclusion, UDCA is not a relevant
      inducer of CYP3A enzymes in humans.

PMID- 15726658
TI  - Pantoprazole reduces the size of postbanding ulcers after variceal band ligation:
      a randomized, controlled trial.
AB  - Elective esophageal variceal ligation (EVL) is performed to decrease the risk of
      variceal hemorrhage. Side effects of EVL include hemorrhage, chest pain,
      dysphagia, and odynophagia. Because gastric acid may exacerbate postbanding
      ulcers and delay healing, proton pump inhibition may decrease side effects
      associated with EVL. The aim of this study was to assess the efficacy of
      pantoprazole, a proton pump inhibitor, as an adjunct to elective EVL. We
      performed a double-blinded, randomized, placebo-controlled trial of pantoprazole
      after elective EVL. Subjects in the pantoprazole arm received 40 mg pantoprazole
      intravenously after EVL followed by 40 mg oral pantoprazole for 9 days. Control
      subjects received intravenous and oral placebo. Subjects underwent upper
      endoscopy 10 to 14 days after banding. Primary outcomes included the size and
      number of ulcers and the subjects' reports of dysphagia, chest pain, and
      heartburn. Forty-four subjects were randomized: 42 completed the protocol. At
      follow-up endoscopy, the mean number of ulcers was similar in the two groups.
      However, the ulcers in the pantoprazole group were on average half as large as in
      the placebo group (37 mm(2) vs. 82 mm(2), P < .01). Chest pain, dysphagia, and
      heartburn scores were not significantly different. Four subjects, all in the
      placebo group, had adverse outcomes, including 3 who bled from postbanding ulcers
      and 1 with sepsis. In conclusion, subjects receiving pantoprazole after elective
      EVL had significantly smaller postbanding ulcers on follow-up endoscopy than
      subjects receiving placebo. However, the total ulcer number and patient symptoms
      were not different between the groups.

PMID- 15726659
TI  - Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal
      rebleeding: a multicenter trial.
AB  - beta-Blockers and endoscopic variceal ligation (EVL) have proven to be valuable
      methods in the prevention of variceal rebleeding. The aim of this study was to
      compare the efficacy of EVL combined with nadolol versus EVL alone as secondary
      prophylaxis for variceal bleeding. Patients admitted for acute variceal bleeding
      were treated during emergency endoscopy with EVL or sclerotherapy and received
      somatostatin for 5 days. At that point, patients were randomized to receive EVL
      plus nadolol or EVL alone. EVL sessions were repeated every 10 to 12 days until
      the varices were eradicated. Eighty patients with cirrhosis (alcoholic origin in
      66%) were included (Child-Turcotte-Pugh A, 15%; B, 56%; C, 29%). The median
      follow-up period was 16 months (range, 1-24 months). The variceal bleeding
      recurrence rate was 14% in the EVL plus nadolol group and 38% in the EVL group (P
      = .006). Mortality was similar in both groups: five patients (11.6%) died in the
      combined therapy group and four patients (10.8%) died in the EVL group. There
      were no significant differences in the number of EVL sessions to eradicate
      varices: 3.2 +/- 1.3 in the combined therapy group versus 3.5 +/- 1.3 in the EVL
      alone group. The actuarial probability of variceal recurrence at 1 year was lower
      in the EVL plus nadolol group (54%) than in the EVL group (77%; P = .06). Adverse
      effects resulting from nadolol were observed in 11% of the patients. In
      conclusion, nadolol plus EVL reduces the incidence of variceal rebleeding
      compared with EVL alone. A combined treatment could lower the probability of
      variceal recurrence after eradication.

PMID- 15726660
TI  - Kupffer cells and macrophages are not required for hepatic hepcidin activation
      during iron overload.
AB  - Hepcidin, the iron hormone, is produced by the liver in response to iron and
      inflammation. Its synthesis during inflammation is triggered by cytokines, but
      the details of iron activation are obscure. We tested the role of Kupffer cells
      and macrophages by studying iron-loaded or inflamed mice with selective
      inactivation of Kupffer cells or the in vitro effect of conditioned human
      macrophages on hepcidin expression. Hepcidin messenger RNA (mRNA) expression was
      studied by Northern blot and reverse transcriptase polymerase chain reaction
      analysis in mice that were treated with 40 mg/kg gadolinium (III) chloride
      (GdCl(3)) as a Kupffer cell inactivating agent and subjected to inflammatory
      challenges with either lipopolysaccharide (LPS) and turpentine or iron overload
      by iron-dextran administration. Similar analyses were performed in human hepatoma
      cells (HepG2) cultured with medium from LPS- or iron-conditioned macrophages from
      blood donors or patients with HFE-linked hereditary hemochromatosis (HH). In
      vivo, LPS and particularly turpentine stimulated hepcidin mRNA expression, and
      this effect was prevented by the inactivation of Kupffer cells. Also, iron
      overload markedly upregulated hepatic hepcidin mRNA, but this activity persisted
      in spite of Kupffer cell blockade. In vitro, the medium of LPS-treated normal or
      hemocromatotic macrophages turned on hepcidin expression. On the contrary, medium
      of iron-manipulated macrophages, regardless of their HFE status, did not affect
      hepcidin mRNA steady-state levels. In conclusion, Kupffer cells are required for
      the activation of hepcidin synthesis during inflammation, and HH inflamed
      macrophages are capable of mounting a normal response, eventually leading to
      hepcidin stimulation. However, both Kupffer cells and human macrophages are
      dispensable for the regulatory activity exerted by iron on hepatic hepcidin.

PMID- 15726661
TI  - Evidence of normal thrombin generation in cirrhosis despite abnormal conventional
      coagulation tests.
AB  - The role played by coagulation defects in the occurrence of bleeding in cirrhosis
      is still unclear. This is partly due to the lack of tests that truly reflect the
      balance of procoagulant and anticoagulant factors in vivo. Conventional
      coagulation tests such as prothrombin time and activated partial thromboplastin
      time are inadequate to explore the physiological mechanism regulating thrombin,
      because they do not allow full activation of the main anticoagulant factor,
      protein C, whose levels are considerably reduced in cirrhosis. We used a thrombin
      generation test to investigate the coagulation function in patients with
      cirrhosis. Thrombin generation measured without thrombomodulin was impaired,
      which is consistent with the reduced levels of procoagulant factors typically
      found in cirrhosis. However, when the test was modified by adding thrombomodulin
      (i.e., the protein C activator operating in vivo), patients generated as much
      thrombin as controls. Hence, the reduction of procoagulant factors in patients
      with cirrhosis is compensated by the reduction of anticoagulant factors, thus
      leaving the coagulation balance unaltered. These findings help clarify the
      pathophysiology of hemostasis in cirrhosis, suggesting that bleeding is mainly
      due to the presence of hemodynamic alterations and that conventional coagulation
      tests are unlikely to reflect the coagulation status of these patients. In
      conclusion, generation of thrombin is normal in cirrhosis. For a clinical
      validation of these findings, a prospective clinical trial is warranted where the
      results of thrombin generation in the presence of thrombomodulin are related to
      the occurrence of bleeding.

PMID- 15726662
TI  - Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats.
AB  - We sought to develop an oral treatment for unconjugated hyperbilirubinemia. In
      the Gunn rat model of unconjugated hyperbilirubinemia, dietary supplementation
      with the lipase inhibitor orlistat (Orl) or with calcium phosphate (CaP)
      decreases plasma unconjugated bilirubin (UCB) levels. We determined whether Orl,
      CaP, or their combination is superior to phototherapy, the conventional
      treatment, and whether the effects of Orl and CaP are influenced by dietary fat
      content. Gunn rats were treated with Orl (200 mg/kg chow), CaP (20 g/kg chow),
      Orl + CaP, or continuous phototherapy (19 muW/cm(2)/nm) during a low-fat (LF)
      diet (13 energy%) or high-fat (HF) diet (35 energy%). Plasma UCB and fecal fat
      excretion were measured before, during, and/or at the end of treatment. Orl
      treatment for 2 weeks (HF diet) reduced plasma UCB concentrations similar to
      phototherapy (-34% and -28%, respectively); the combination of both was more
      effective than either treatment alone (-48%; P < .001). After 3 weeks of a HF
      diet, plasma UCB was 46% lower compared with the LF diet (P < .001). Plasma UCB
      concentrations were negatively correlated with fecal fat excretion (r = -0.96; P
      < .001). Irrespective of dietary fat content, 3 weeks of combined treatment (Orl
      + CaP) decreased plasma UCB by approximately 50% (P < .01) and was more effective
      than phototherapy (P < .05) at the intensity provided. In conclusion, plasma UCB
      concentrations in Gunn rats are negatively related to fecal fat excretion and
      dietary fat content. Orlistat is equally effective as phototherapy for the
      treatment of unconjugated hyperbilirubinemia in Gunn rats, and combined oral
      treatment with Orl + CaP is more effective than phototherapy. The present results
      support the feasibility of an efficient oral treatment of unconjugated
      hyperbilirubinemia.

PMID- 15726664
TI  - Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial
      lymphocytes of intrahepatic bile ducts.
AB  - Fractalkine is a chemokine with both chemoattractant and cell-adhesive functions,
      and in the intestine it is involved with its receptor CX3CR1 in the
      chemoattraction and recruitment of intraepithelial lymphocytes. We examined the
      pathophysiological roles of fractalkine and CX3CR1 in normal and diseased bile
      ducts. Expression of fractalkine and CX3CR1 were examined in liver tissues from
      patients with primary biliary cirrhosis (17 cases) and controls (9 cases of
      primary sclerosing cholangitis, 10 cases of extrahepatic biliary obstruction, 20
      cases of chronic viral hepatitis C, and 18 cases of histologically normal
      livers). Expression of fractalkine in biliary epithelial cells (BECs) in response
      to cytokine treatments was examined using a human cholangiocarcinoma cell line
      (HuCC-T1) and human intrahepatic BEC line. The chemotaxis of CX3CR1-expressing
      monocytes (THP-1) toward fractalkine was assayed using chemotaxis chambers.
      Fractalkine messenger RNA/protein were expressed on BECs of normal and diseased
      bile ducts, and their expression was upregulated in injured bile ducts of primary
      biliary cirrhosis. CX3CR1 was expressed on infiltrating mononuclear cells in
      portal tracts and on CD3(+), CD4(+), and CD8(+) intraepithelial lymphocytes of
      injured bile ducts in primary biliary cirrhosis. Fractalkine messenger RNA
      expression was upregulated in two cultured BECs on treatment with
      lipopolysaccharide and Th1-cytokines (interleukin 1beta, interferon gamma, and
      tumor necrosis factor alpha). THP-1 cells showed chemotaxis toward fractalkine
      secreted by cultured cells. In conclusion, Th1-cytokine predominance and
      lipopolysaccharide in the microenvironment of injured bile ducts resulting from
      primary biliary cirrhosis induce the upregulation of fractalkine expression in
      BECs, followed by the chemoattraction of CX3CR1-expressing mononuclear cells,
      including CD4(+) and CD8(+) T cells, and their adhesion to BECs and the
      accumulation of biliary intraepithelial lymphocytes.

PMID- 15726663
TI  - Transdifferentiation of rat hepatocytes into biliary cells after bile duct
      ligation and toxic biliary injury.
AB  - Rats with chimeric livers were generated by using the protocol of injecting
      hepatocytes from dipeptidyl peptidase IV (DPPIV)-positive donors into retrorsine
      treated DPPIV-negative recipients subjected to partial hepatectomy. Rats with
      established chimeric livers were subjected to bile duct ligation, with or without
      pretreatment with the biliary toxin methylene diamiline (DAPM). Ductules bearing
      the donor hepatocyte marker DPPIV were seen at 30 days after bile duct ligation.
      The frequency of the ductules derived from the donor hepatocytes was dramatically
      enhanced (36-fold) by the pretreatment with DAPM. In conclusion, our results show
      that hepatocytes can function as facultative stem cells and rescue the biliary
      epithelium during repair from injury when its proliferative capacity is being
      compromised.

PMID- 15726665
TI  - Keratin mutation primes mouse liver to oxidative injury.
AB  - Mutation of the cytoskeletal intermediate filament proteins keratin 8 and keratin
      18 (K8/K18) is associated with cirrhosis in humans, whereas transgenic mice that
      overexpress K18 Arg89-->Cys (R89C) have significant predisposition to liver
      injury. To study the mechanism of keratin-associated predisposition to liver
      injury, we used mouse microarrays to examine genetic changes associated with
      hepatocyte keratin mutation and assessed the consequences of such changes. Liver
      gene expression was compared in R89C versus nontransgenic or wild-type K18
      overexpressing mice. Microarray-defined genetic changes were confirmed by
      quantitative polymerase chain reaction. Nineteen genes had a more than two-fold
      altered expression (nine downregulated, 10 upregulated). Upregulated genes in
      keratin-mutant hepatocytes included the oxidative metabolism genes cytochrome
      P450, S-adenosylhomocysteine (SAH) hydrolase, cysteine sulfinic acid
      decarboxylase, and oxidation-reduction pathway genes. Downregulated genes
      included fatty acid binding protein 5, cyclin D1, and some signaling molecules.
      Several methionine metabolism-related and glutathione synthetic pathway
      intermediates, including S-adenosylmethionine (SAMe) and SAH, were modulated in
      R89C versus control mice. R89C livers had higher lipid and protein oxidation by
      products as reflected by increased malondialdehyde and oxidized albumin. In
      conclusion, K18 point mutation in transgenic mice modulates several hepatocyte
      oxidative stress-related genes and leads to lipid and protein oxidative by
      products. Mutation-associated decreases in SAH and SAMe could compromise needed
      cysteine availability to generate glutathione during oxidative stress. Hence
      keratin mutations may prime hepatocytes to oxidative injury, which provides a new
      potential mechanism for how keratin mutations may predispose patients to
      cirrhosis.

PMID- 15726666
TI  - Regression models for the analysis of longitudinal Gaussian data from multiple
      sources.
AB  - We present a regression model for the joint analysis of longitudinal multiple
      source Gaussian data. Longitudinal multiple source data arise when repeated
      measurements are taken from two or more sources, and each source provides a
      measure of the same underlying variable and on the same scale. This type of data
      generally produces a relatively large number of observations per subject; thus
      estimation of an unstructured covariance matrix often may not be possible. We
      consider two methods by which parsimonious models for the covariance can be
      obtained for longitudinal multiple source data. The methods are illustrated with
      an example of multiple informant data arising from a longitudinal interventional
      trial in psychiatry.

PMID- 15726667
TI  - Ex vivo expansion of human cytomegalovirus-specific cytotoxic T cells by
      recombinant polyepitope: implications for HCMV immunotherapy.
AB  - Stem cell transplantation (SCT) remains the most effective curative therapy for
      the majority of hematopoietic malignancies. Unfortunately, SCT is limited by its
      toxicity and infectious complications that result from profound
      immunosuppression. In particular, acquisition of exogenous or reactivation of
      endogenous human cytomegalovirus (HCMV) is common after SCT. More recently,
      reconstitution of host immunity through augmentation of anti-HCMV T cell
      responses has been proposed as an exciting candidate therapy to avoid the
      requirement for antiviral drug use. Here we have developed a novel antigen
      presentation system based on a replication-deficient adenovirus that encodes
      multiple HLA class I-restricted epitopes from eight different antigens of HCMV as
      a polyepitope (referred to as AdCMVpoly). Ex vivo stimulation of peripheral blood
      mononuclear cells with AdCMVpoly consistently showed rapid stimulation and
      expansion of multiple epitope-specific T cells that recognized endogenously
      processed epitopes presented on virus-infected cells. Interestingly, the
      AdCMVpoly expression system is capable of expanding antigen-specific T cells even
      in the absence of CD4(+) T cells. These studies show the effectiveness of a
      polyepitope antigen presentation system for reproducible expansion of antigen
      specific T cells from immunocompetent and immunocompromised settings.

PMID- 15726668
TI  - Revitalization of academic medicine: looking into the future.

PMID- 15726669
TI  - The Cri$i$ in academic medicine.
AB  - Many believe that academic medicine is failing to meet all of its
      responsibilities and is in crisis. We interviewed a number of distinguished
      academicians and, while they held different views, found agreement that academic
      medical centers in the USA have gradually changed during the past half century
      from small, cloistered, scholarly institutions to large, complex, corporate-style
      organizations. These changes were fueled by large contributions of funds for
      research and great research accomplishments. However, these institutions seem to
      have insatiable needs for more money, which refocuses institutional culture,
      making them behave more like business corporations. The result is very high
      tuitions, enormous student debt burdens, and pressure on young academicians to
      become self-supporting more quickly. Almost all non-compensated activities,
      especially teaching, suffer. Since clinical care pays an increasing portion of
      school operating revenue, those who teach and do research are under increasing
      pressure to provide more clinical care, to see more patients per unit of time and
      do more procedures, resulting in fatigue, less time for teaching and research,
      and less gratification for doctors and patients. Attention to community needs and
      providing help to academic medicine in less developed nations are very low
      priorities. Academic medicine appears on the surface to be vigorous and healthy
      but is at risk of imploding. The heads of academic centers, working together,
      must be charged to create plans to restore a healthy culture.

PMID- 15726670
TI  - Revitalization of academic medicine in Albania.
AB  - The Faculty of Medicine in Tirana, the only institution providing medical
      training in Albania, has currently developed three separate branches of study,
      General Medicine, Dentistry, and Pharmacy. Since the early 1990s, following the
      collapse of the communist regime, many faculty members have been trained abroad
      in different areas of medical sciences. Yet, little emphasis is placed on
      research work and teaching of evidence-based medicine in both, undergraduate and
      postgraduate studies. Medical students are not exposed to sources of evidence,
      searching techniques, and important medical databases, such as PubMed and
      Cochrane Library. Exposing medical students and young physicians to probabilistic
      thinking, the importance of communication, and levels of evidence in medical
      practice is what the academic medicine in Albania should strive for. To address
      this challenge, the Faculty of Medicine in Tirana needs to strengthen the
      mobility of its students and their training in Western schools. These young and
      well-trained faculty members will provide the critical mass of future
      academicians required to develop a modern medical school in Tirana.

PMID- 15726671
TI  - Transition of the medical curriculum from classical to integrated: problem-based
      approach and Australian way of keeping academia in medicine.
AB  - The world-wide trend of changing medical curricula from the "old," didactic and
      discipline based to the "new," integrated, Problem-based Learning (PBL) approach
      did not bypass Australian shores. It has thoroughly shaken the foundations of
      dogmatic concepts of medical (particularly pre-clinical) education by posing
      challenges initially to the basic sciences departments . The "point of no-return"
      was reached very early when the Faculty Education Unit was established with an
      initial aim to lead and support the transition. Regarding the new curriculum the
      emotions among academics varied from quiet skepticism and mild resistance to open
      confrontation and refusal to participate in the process. Just after we were
      convinced that spending a lot of our academic time on developing new material for
      integrated self-directed learning was the worst part, the transition period with
      double teaching (which stretched our resources to the limits) was even worse. The
      first generation of "reformed" students graduated last year. In this article I
      will present unique and original concepts introduced into the PBL based medical
      course at the University of Melbourne. I will particularly highlight efforts to
      expose medical students to the real research environment and the "academic way of
      thinking" in order to create health professionals with an ongoing interest in
      medical research. I will also (subjectively) reflect on the course and share with
      you some of my impressions and experiences from the point of view of a pre
      clinical academic trying to balance his multi vocational profession.

PMID- 15726672
TI  - Is there any solution to the "brain drain" of health professionals and knowledge
      from Africa?
AB  - African public health care systems suffer from significant "brain drain" of its
      health care professionals and knowledge as health workers migrate to wealthier
      countries such as Australia, Canada, USA, and the United Kingdom. Knowledge
      generated on the continent is not readily accessible to potential users on the
      continent. In this paper, the brain drain is defined as both a loss of health
      workers (hard brain drain) and unavailability of research results to users in
      Africa (soft brain drain). The "pull" factors of "hard brain drain" include
      better remuneration and working conditions, possible job satisfaction, and
      prospects for further education, whereas the "push" factors include a lack of
      better working conditions including promotion opportunities and career
      advancement. There is also a lack of essential equipment and non-availability or
      limited availability of specialist training programs on the continent. The causes
      of "soft brain drain" include lack of visibility of research results in African
      journals, better prospects for promotion in academic medicine when a publication
      has occurred in a northern high impact journal, and probably a cultural
      limitation because many things of foreign origin are considered superior.
      Advocates are increasingly discussing not just the pull factors but also the
      "grab" factors emanating from the developed nations. In order to control or
      manage the outflow of vital human resources from the developing nations to the
      developed ones, various possible solutions have been discussed. The moral regard
      to this issue cannot be under-recognized. However, the dilemma is how to balance
      personal autonomy, right to economic prosperity, right to personal professional
      development, and the expectations of the public in relation to adequate public
      health care services in the developing nations.

PMID- 15726673
TI  - Why does man have a quadratus plantae? A review of its comparative anatomy.
AB  - Quadratus plantae is a muscle in the sole of the foot, typically originating from
      the calcaneus and inserting into the posterolateral surface of the tendons of
      flexor digitorum longus. It is implicated in heel pain, claw toe deformity and
      diabetic polyneuropathy. Phylogenetic considerations suggest that quadratus
      plantae is getting bulkier, implying its significance in human locomotion. Is it
      simply an accessory flexor that brings the line of pull of flexor digitorum
      longus in line with the long axis of the foot, as its name would suggest? We cite
      evidence from electromyographic studies that suggest it actually acts as a
      primary toe flexor in voluntary movements, being preferentially recruited over
      flexor digitorum longus. From comparative anatomical considerations it also seems
      likely that quadratus plantae is an intrinsic evertor of the foot. Eversion is an
      important evolutionary asset, especially in erect bipedalism. Human
      electromyographic experiments have yet to confirm this. However, they do suggest
      that quadratus plantae functions to resist extension of the toes during the
      stance phase of locomotion, which serves to increase the stability of the foot.
      Future electromyographic experiments may provide more information on the role of
      quadratus plantae in human locomotor evolution and in foot eversion in
      particular.

PMID- 15726674
TI  - Maternal ratings of temperamental characteristics of healthy premature infants
      are indistinguishable from those of full-term infants.
AB  - AIM: To investigate whether prematurity itself, if not accompanied with serious
      medical risks, affects early temperamental characteristics, as measured by
      maternal ratings. METHODS: Mothers' reports on temperamental characteristics of
      104 low-risk, healthy premature infants were compared with those from a
      comparable sample of 120 full-term infants. Mothers completed the Infant Behavior
      Questionnaire (IBQ) when their infants were 6 or 12 months old (corrected for
      prematurity for premature infants). RESULTS: Two groups of infants significantly
      differed only in one of six IBQ scales, the Activity Level scale, with premature
      infants being rated by their mothers as more active than full-term infants
      (ANOVA, P=0.026). Most of the interactions of prematurity with age and sex were
      insignificant, as well as the main effects of age and sex. Furthermore, effect
      sizes (Cohen's d) were relatively small, even for statistically significant
      effects. Correlation analyses performed within the premature sample showed that
      premature infants' gestational ages at birth did not significantly correlate with
      IBQ scales, except with Duration of Orienting scale, on which more premature
      infants were rated as having shorter periods of orienting (r=0.21, P=0.036).
      CONCLUSION: Ratings of premature infants' mothers on five out of six temperament
      dimensions measured in the study were indistinguishable from those of full-term
      infants' mothers. As the study had high power of achieving significant effects of
      prematurity if they really existed, it can be concluded that prematurity per se,
      if not accompanied with serious medical problems, did not have profound influence
      on mothers' ratings of infant temperament.

PMID- 15726675
TI  - Sexual problems of urban women in Croatia: prevalence and correlates in a
      community sample.
AB  - AIM: To asses the prevalence and correlates of female sexual problems in a
      community sample in the Croatian capital of Zagreb. METHOD: The study was based
      on a self-administered postal survey of 1,170 women 20-60 years old, living in
      Zagreb. The return rate was 48% (n=547). Participants not sexually active in the
      last month (n=119), and those who self-identified as homosexual or bisexual
      (n=31), were excluded from the analyses. The final sample consisted of 384 women.
      The average age of participants was 38.2 years. Four categories of sexual
      problems were addressed: inhibited sexual desire, inhibited sexual arousal,
      inhibited orgasm, and sexual pain disorders. RESULTS: Of the heterosexual women
      sexually active in the last month, 33.8% experienced sexual problems, with
      inhibited orgasm being the most frequent problem. Comorbidity was recorded among
      10.7% of the participants. Older age was positively related to inhibited desire
      (beta=0.11, P=0.05) and inhibited arousal (beta=0.25, P=0.002), whereas it was
      negatively related to inhibited orgasm and sexual pain disorders (beta=-3.73,
      P=0.001 and beta=-6.98, P=0.01, respectively). Length of relationship was
      positively related to inhibited desire (beta=1.17, P=0.016). Religious morality
      was positively related to inhibited desire, inhibited arousal, and sexual pain
      disorders (beta=0.43, P<0.001, beta=0.52, P=0.001, and beta=0.11, P=0.044,
      respectively). Intimate communication was negatively related to inhibited desire,
      inhibited arousal, and inhibited orgasm (beta=-2.18, P<0.001, beta=-2.67,
      P<0.001, and beta=-0.21, P=0.003, respectively); and body image was negatively
      related to inhibited arousal and sexual pain disorders (beta=-1.17, P=0.026 and
      beta=-0.38, P=0.042, respectively). CONCLUSION: Sexual health disturbances among
      urban Croatian women are frequent. Their prevalence calls for incorporating
      sexual health issues in the national public health agenda. Multifaceted character
      of sexual problems is important for adult sexuality education and counseling.

PMID- 15726676
TI  - Development and validation of questionnaire measuring attitudes towards sexual
      health among university students.
AB  - AIM: To develop a questionnaire on attitudes towards sexual health and validate
      it on a sample of medical and non-medical students and adult women. METHODS: For
      the purpose os constructing a Likert-type scale, four medical studentsgenerated
      130 statements reflecting clearly positive or negative attitudes towards sexual
      health. The scale had five scoring points (1 - strongly disagree, 2 - disagree, 3
      - undecided, 4 - agree, and 5 - strongly agree). We revised the items to ensure
      that all were clearly positive or clearly negative in their form, as well as
      straightforward in their meaning, leaving 100 items in the raw questionnaire,
      which was then applied to the convenience sample (total n=336) of female medical
      students (n=93), male medical students (n=75), female non-medical students (n=93)
      and adult working women with at least high-school education (n=75). After the
      administration of the questionnaire, we performed content examination,
      discriminant validation of the statements, and principal-components analysis.
      RESULTS: After discriminant validation of the statements and principal-components
      analysis limited to three factors, the final scale contained 50 items (20
      positive and 30 negative), distributed in three subscales: "Personal sexual
      health care," "Principles of sexual behavior," and "Safe sex behavior." The
      Cronbach alpha of the whole scale was 0.910, indicating good internal
      consistency. When the scores of the final scale were analyzed for the study
      sample, all participants had positive attitude towards sexual health, with a mean
      score (+/-standard deviation) of 4.1+/-0.4 out of maximum 5. The same was true
      for all threee subscales. Female groups, regardless of their student status or
      age, did not differ in their attitude scores on the whole scale, as well as on
      any of the subscales. Male medical students had lower scores on the whole scale
      and all subscales than the female groups. CONCLUSIONS: It is posible to construct
      a reliable instrument to assess attitudes towards three important aspects of
      sexual health: personal sexual health care, sexual behavior, and safe sex
      behavior. Future studies with this instrument, on different populations and in
      different cultural and socio-economic settings, are needed to make generalized
      conclusions on sexual health attitudes and behavior.

PMID- 15726677
TI  - Factors associated with academic success at Vienna Medical School: prospective
      survey.
AB  - AIM: To identify factors relating to students' success in the study of medicine
      at the Medical University of Vienna. In view of Austria's tradition of open
      access to higher education, which results large number of students, high dropout
      rate, long duration of studies, factors predicting success could be helpful for
      student counseling. METHODS: In a prospective study, 674 freshmen (50.8% of
      students enrolled that year) responded to a questionnaire on their
      sociodemographic data, family background, performance in school, economic
      situation, living conditions, social integration and health, learning capacity,
      motivations related to studies and future profession, attitudes, and the ability
      to cope with stress. We used the results of the compulsory test of knowledge
      after the first year as an outcome measure of their success. RESULTS: By
      comparing two extremes of academic success, very successful students and students
      who twice failed the challenging first-year exam, we were able to identify three
      factors relevant in predicting academic success: male sex, German as mother
      tongue, and good performance in secondary school. Moreover, there is evidence
      that maturity and intrinsic motivational structure are linked to superior
      academic performance. CONCLUSION: The results of this study differ from or even
      contradict the findings of previous retrospective studies in Austria. We suggest
      that a more thorough examination of the effect of gender should be undertaken in
      future studies. We also hope that our work will lead to the improvement in the
      efficiency of the German courses for foreign students. Our findings confirm the
      importance of success in secondary school, but also clearly indicate that it
      should not be the only criterion for university admission.

PMID- 15726678
TI  - Socioeconomic factors and health risk behaviors among university students in
      Turkey: questionnaire study.
AB  - AIM: To explore relations between socioeconomic factors and health risk behaviors
      in university students in Turkey. METHODS: A total of 650 students currently
      enrolled at the university in Ankara were selected for the study by means of a
      circular sampling method. They answered a questionnaire on health risk behaviors.
      We used multivariate analysis to analyze the relations between socioeconomic
      variables and each of the following participants' behaviors in the last year: use
      of cigarettes, alcohol, or drugs; driving under the influence of alcohol;
      unprotected sex; attempted suicide; self-mutilation; physical fighting; carrying
      firearms or edged weapon; not wearing a safety belt in motor vehicles; or riding
      a motorcycle without a helmet. RESULTS: Health risk behaviors in university
      students were in general related to low socioeconomic status, except for alcohol
      use, which was related to high socioeconomic status. Among female students whose
      mothers had completed high school, 81.9% used alcohol, compared with less than
      68% of female students whose mothers had not completed high school or had
      completed university (P<0.001). Also, 4.0% of female students whose mothers had
      completed high school had attempted suicide, compared with less than 1.5% of
      female students whose mothers had not completed high school or had completed
      university (P=0.026). In male students, important variables were parental
      education level and paternal employment status. Among male students who had
      unemployed fathers, 66.7% used cigarettes (P=0.015), 26.7% engaged in substance
      use (P<0.010), and 4.4 % attempted suicide (P<0.050) in comparison with 11.9 and
      0.7%, respectively, of male students whose fathers were employed. Logistic
      regression showed male gender to be associated with an increase in all risk
      behaviors (odds ratio 1.114, 95% confidence interval 1.652-5.622, P<0.001).
      CONCLUSION: This study confirms the findings of similar studies in western
      developed countries, suggesting that relations between socioeconomic variables
      and health risk behaviors in young people reflect a basic phenomenon not greatly
      influenced by culture.

PMID- 15726679
TI  - Content of home pharmacies and self-medication practices in households of
      pharmacy and medical students in Zagreb, Croatia: findings in 2001 with a
      reference to 1977.
AB  - AIM: To evaluate the content of household drug supplies and self-medication
      practice among medical and pharmacy students at Zagreb University in 2001, and to
      relate the findings to a previous survey in 1977. METHODS: A cross-sectional
      anonymous questionnaire-based survey included 287 students who inventoried drug
      supplies in their family households and interviewed the household members on drug
      keeping and self-medication practice. An identical methodology was used in 1977
      (n=225). RESULTS: In 2001, healthcare professionals were present in 37% of the
      surveyed households (33% in 1977). At least one drug was found in every
      household. Drugs were kept at a designated place ("home pharmacy") in 68% of the
      households (65% in 1977). Drugs past expiry dates and/or with purpose unknown to
      the household members were reported in 27% of the households (32% in 1977). The
      most frequently found drugs were non-steroidal anti-inflammatory drugs (NSAIDs)
      that were present in 97% of the households (93% in 1977), and were followed by
      antibiotics found in 46% of the households (40% in 1977). Self-medication of
      NSAIDs was practiced in 88% of the households in which they were found (95% in
      1977), whereas self-medication of antibiotics was practiced in 37% of the
      households in which they were found (41% in 1977). CONCLUSION: Accumulation of
      drugs was common in the surveyed households. Self-medication of over-the-counter
      drugs was a routine practice, and self-medication of prescription drugs was
      practiced in many households. No major difference in this respect was found
      between the 2001 and 1977 surveys.

PMID- 15726680
TI  - Assessment of psychological and social factors in adolescents risk behavior:
      questionnaire study.
AB  - AIM: To investigate the influence of psychological and social factors on health
      risk behaviors, such as smoking, alcohol and psychoactive drug consumption among
      adolescents and to determine the prevalence of consuming various psychoactive
      substances. METHODS: The survey was conducted among adolescents in the Primorsko
      goranska County in Croatia in 2003. The prevalence of smokers, alcohol, and
      psychoactive drugs consumers and abstainers, with general and specific predictors
      for the development of risk behavior of 2,452 adolescents in Primorsko-goranska
      County was determined by means of valid self-reported questionnaires. The
      adolescents were stratified according to gender and type of secondary school.
      RESULTS: Every third student smoked cigarettes every day, and 73% consumed beer,
      wine, and alcoholic beverages occasionally. The percentage of illicit drugs
      consumption (experimental, occasional and regular) ranged from 2,3% for opiates
      to 35.6 for marihuana. Girls consumed more cigarettes, alcoholic beverages, and
      sedatives every day, whereas boys consumed more beer, wine, and marihuana.
      Consumption of all psychoactive substances was more prevalent among senior
      students. A moderate correlation was found between addictive resources
      consumption and negative peer influence and ways of spending free time.
      CONCLUSION: Most adolescents had personal experience with psychoactive substance
      use, mostly tobacco, alcohol, and marihuana. The strongest predictors were
      negative peer influence and ways of spending free time. These findings may be
      useful for formulating strategies for prevention of addiction among adolescents.

PMID- 15726681
TI  - Research involvement, specialty choice, and emigration preferences of final year
      medical students in croatia.
AB  - AIM: To explore involvement in scientific research, choice of specialty, and
      readiness to emigrate among graduating medical students in Croatia. METHODS: A
      total of 312 out of 408 (76%) final year medical students of all Croatian Medical
      Schools (Zagreb, Rijeka, Osijek, and Split) graduating in 2004 answered a
      questionnaire designed for this study, including questions on scientific
      involvement, desired specialty, and emigration preferences. RESULTS: During
      undergraduate study, 71 (23%) students have been involved in scientific projects.
      However, only 27 of them (38%) succeeded in publishing their results. Students
      identified poor project management as the most common reason for publication
      failure. Specialty choice varied among the four medical schools in Croatia but
      internal medicine, pediatrics, and surgery were usually highly preferred in all
      schools. If they failed to get the desired specialty, 104 (33%) students would
      consider emigration. CONCLUSION: There is a clear need for improvement in the
      management of students' research projects in Croatia, enabling enthusiastic
      medical students to publish the results of their work and retain their interest
      in science. The analysis of change of the desired specialties throughout the
      undergraduate study suggests an increased interest in the "controllable
      lifestyle" specialties. Failure to get the desired specialty would result in
      emigration for many students.

PMID- 15726682
TI  - Depressive symptomatology among university students in Denizli, Turkey:
      prevalence and sociodemographic correlates.
AB  - AIM: To determine overall and subgroup prevalence of depressive symptomatology
      among university students in Denizli, Turkey during the 1999-2000 academic year,
      and to investigate whether sociodemographic factors were associated with
      depressive symptoms in university students. METHODS: A stratified probability
      sample of 504 Turkish university students (296 male, 208 female) was used in a
      cross-sectional study. Data were obtained by self-administered questionnaire,
      including questions on sociodemographic characteristics and problem areas. The
      revised Beck Depression Inventory (BDI) was used to determine depressive symptoms
      of the participants. BDI scores 17 or higher were categorized as depressive for
      logistic regression analysis. Student t-test and linear regression were used for
      continuous data analysis. RESULTS: Out of all participants, 26.2% had a BDI score
      17 or higher. The prevalence of depressive symptoms increased to 32.1% among
      older students, 34.7% among students with low socioeconomic status, 31.2% among
      seniors, and 62.9% among students with poor school performance. The odds ratio of
      depressive symptoms was 1.84 (95% confidence interval [CI], 1.03-3.28) in
      students with low socioeconomic status and 7.34 (95% CI, 3.36-16.1) in students
      with poor school performance in the multivariate logistic model. The participants
      identified several problem areas: lack of social activities and shortage of
      facilities on the campus (69.0%), poor quality of the educational system (54.8%),
      economic problems (49.3%), disappointment with the university (43.2%), and
      friendship problems (25.9%). CONCLUSIONS: Considering the high frequency of
      depressive symptoms among Turkish university students, a student counseling
      service offering mental health assistance is necessary. This service should
      especially find the way to reach out to poor students and students with poor
      school performance.

PMID- 15726683
TI  - Nurses' attitudes towards computers: cross sectional questionnaire study.
AB  - AIM: To estimate the attitudes of hospital nurses towards computers and the
      influence of gender, age, education, and computer usage on these attitudes.
      METHODS: The study was conducted in two Croatian hospitals where integrated
      hospital information system is being implemented. There were 1,081 nurses
      surveyed by an anonymous questionnaire consisting of 8 questions about
      demographic data, education, and computer usage, and 30 statements on attitudes
      towards computers. The statements were adapted to a Likert type scale.
      Differences in attitudes towards computers were compared using one-way ANOVA and
      Tukey-b post-hoc test. RESULTS: The total score was 120+/-15 (mean+/-standard
      deviation) out of maximal 150. Nurses younger than 30 years had a higher total
      score than those older than 30 years (124+/-13 vs 119+/-16 for 30-39 age groups
      and 117+/-15 for>39 age groups, P<0.001). Nurses with a bachelor's degree (119+/
      16 vs 122+/-14, P=0.002) and nurses who had attended computer science courses had
      a higher total score compared to the others (124+/-13 vs 118+/-16, P<0.001).
      Nurses using computers more than 5 hours per week had higher total score than
      those who used computers less than 5 hours (127+/-13 vs 124+/-12 for 1-5 h and
      and 119+/-14 for <1 hour per day, P<0.001, post-hoc test). CONCLUSION: Nurses in
      general have positive attitudes towards computers. These results are important
      for the planning and implementing an integrated hospital information system.

PMID- 15726684
TI  - Acculturation and psychological problems of adolescents from Bosnia and
      Herzegovina during exile and repatriation.
AB  - AIM: To estimate the frequency, type, and severity of psychological trauma among
      Bosnian refugee adolescents during the process of repatriation after the 1992
      1995 war in Bosnia and Herzegovina. METHODS: A sample of 239 pupils (120 girls
      and 119 boys), with a mean age (+/-standard deviation) of 15.2+/-2.1 years were
      assessed for war traumatic events, acculturation and repatriation maladjustments,
      school behavioral problems, and presence of post-traumatic stress disorder
      (PTSD). The sample consisted of adolescents who were in the process of
      repatriation after exile in a foreign country (n=120) and internally displaced
      adolescents (n=119). RESULTS: Adolescents who had been exposed to severe
      psychological war trauma still had high level of trauma more than three years
      after the end of war. The level of recalling traumas they experienced (mean+/
      standard deviation=3.9+/-1.2 on a scale from 0 to 5) and frequency of PTSD
      symptoms (1.5+/-1.0 on a scale from 0-5) were significantly lower among
      repatriated than internally displaced adolescents (4.4+/-0.7 and 2.2+/-1.1,
      respectively; P<0.001). The prevalence of PTSD did not differ between repatriated
      (56.7%) and internally displaced adolescents (68.1%). Returnees with more
      acculturation problems reported more functional and relational problems after
      return but less psycho-emotional dysfunctions. Those who adapted to the culture
      in the exile country had difficulties in adapting back to the culture in the home
      country. CONCLUSIONS: PTSD was still very frequent among Bosnian refugee
      adolescents 3.5 years after the end of war. Adolescents who had spent more than
      five years as refugees in foreign countries had significantly lower level of
      experienced trauma recall and frequency of PTSD symptoms, as well as less
      anxious/depressed and withdrawn/depressed behavioral problems, and somatic
      complaints. Returnees who had more acculturation problems in exile reported more
      functional and relational problems but less psycho-emotional problems after
      repatriation. Schools and other institutions involved in the education of
      adolescents should develop programs to address these issues.

PMID- 15726685
TI  - Endemic nephropathy: the case for chronic poisoning by aristolochia.
AB  - AIM: To explore the hypothesis that chronic dietary poisoning by aristolochic
      acid could account for the unique geographical distribution, specific pattern of
      tubulointerstitial fibrosis, occurrence of chronic renal insufficiency, and an
      increased risk of developing upper urothelial cancer, all of which are associated
      with endemic nephropathy. METHODS: This case-controlled epidemiologic study
      consisted of three groups of subjects residing in an endemic region of Croatia:
      (a) patients meeting WHO criteria for endemic nephropathy (n=28), (b) individuals
      who have been treated for renal insufficiency secondary to other forms of renal
      disease (n=30), and (c) apparently healthy residents of the endemic village (n=
      30). A detailed questionnaire, designed to collect information on demographics,
      exposure to potentially toxic substances, diet, agricultural practices, and other
      factors potentially impacting endemic nephropathy was administered to the three
      study groups. The seeds of Aristolochia clematitis, obtained from plants growing
      in the endemic region, were extracted with ethanol and analyzed by high
      performance liquid chromatography for their aristolochic acid content. RESULTS:
      The majority of subjects, including 90% of endemic nephropathy patients, recall
      that the plant Aristolochia clematitis (birthwort, vucja stopa in Croatian) was
      frequently found in local meadows and wheat fields between 20 and 30 years ago.
      At that time, endemic nephropathy patients encountered Aristolochia clematitis
      significantly more frequently than controls (P=0.035). Since then, all three
      study groups reported a significant increase in the use of herbicides (P<0.001)
      and reduction in the prevalence of Aristolochia clematitis (P<0.001). Chemical
      analysis established that the seeds of A. clematitis contain 0.65% aristolochic
      acid. It is likely that the harvesting process used by local farmers permitted
      the seeds of A. clematitis to mingle with the wheat grain. CONCLUSION: Flour used
      to bake bread, a dietary staple in the endemic region of Croatia, is derived from
      wheat grain which, in the past, is likely to have been contaminated with seeds of
      A. clematitis during harvesting. This observation supports the hypothesis that
      aristolochic acid, a major constituent of the seeds, plays a central role in the
      development of endemic nephropathy.

PMID- 15726686
TI  - Prevalence of plagiarism among medical students.
AB  - AIM: To determine the prevalence of plagiarism among medical students in writing
      essays. METHODS: During two academic years, 198 second year medical students
      attending Medical Informatics course wrote an essay on one of four offered
      articles. Two of the source articles were available in an electronic form and two
      in printed form. Two (one electronic and one paper article) were considered less
      complex and the other two more complex. The essays were examined using plagiarism
      detection software "WCopyfind," which counted the number of matching phrases with
      six or more words. Plagiarism rate, expressed as the percentage of the
      plagiarized text, was calculated as a ratio of the absolute number of matching
      words and the total number of words in the essay. RESULTS: Only 17 (9%) of
      students did not plagiarize at all and 68 (34%) plagiarized less than 10% of the
      text. The average plagiarism rate (% of plagiarized text) was 19% (5-95%
      percentile=0-88). Students who were strictly warned not to plagiarize had a
      higher total word count in their essays than students who were not warned
      (P=0.002) but there was no difference between them in the rate of plagiarism.
      Students with higher grades in Medical Informatics exam plagiarized less than
      those with lower grades (P=0.015). Gender, subject source, and complexity had no
      influence on the plagiarism rate. CONCLUSIONS: Plagiarism in writing essays is
      common among medical students. An explicit warning is not enough to deter
      students from plagiarism. Detection software can be used to trace and evaluate
      the rate of plagiarism in written student assays.

PMID- 15726687
TI  - Why choose Lent for a "smoke out day?" Changing smoking behavior in Croatia.
AB  - AIM: To evaluate the impact on smokers' behavior of public health activity
      related to a religious event such as Lent in a predominantly Roman Catholic
      country. METHODS: "Smoke out day" was organized on the first day of Lent, a
      period of self-denial for Roman Catholics, combining cultural and religious
      significance for Croatian people. The day was covered by a massive media
      campaign. Smoking behavior and attitudes to smoking were examined using a cross
      sectional anonymous survey, conducted among 2,143 TV viewers and radio listeners
      aged 15 and older in their households. RESULTS: More than 75% of the interviewed
      persons knew the exact date of the "Smoke out day." Among smokers, 27% had given
      up smoking on that day and 16% declared they would not smoke during Lent.
      Significantly more women (34%) than men (23%) abstained from smoking on the
      "Smoke out day" and more women (24% vs 10.8%) had decided to abstain from smoking
      during Lent. The majority of abstainers were in the 30-44 age group. The lowest
      response to antismoking campaign was from smokers with university education.
      CONCLUSION: Antismoking mass media activity can influence smokers' behavior
      especially if it is connected to cultural and religious aspects. Some groups are
      much more sensitive to this kind of activities and may be, with a good media
      campaign and developed network of professional help and support, supported to
      transform their "Smoke out day" into a lifelong abstinence.

PMID- 15726689
TI  - An epidemic is threatening health care worldwide.

PMID- 15726688
TI  - Identification of population groups at very high risk for frequent perception of
      stress in slovenia.
AB  - AIM: To identify population groups at very high risk for frequent perception of
      stress and thus enable more focused planning of prevention actions in Slovenia.
      METHODS: Data originate from the national survey carried out in 2001 on health
      behavior of 15,379 adults aged 25-64. The overall response rate of the mailed
      questionnaire was 64%, with 9,043 questionnaires eligible for analysis. Binary
      multiple logistic regression was used to determine the impact of gender, age,
      education, employment, self-assessed social class, type of residence community,
      and geographical region on the prevalence of frequent stress perception. RESULTS:
      The highest odds for stress were registered in women (OR(women vs men)=1.39,
      P<0.001), aged 40-49 years (OR(40-49 vs 30-39)=1.18, p=0.017; OR(50-59 vs 40
      49)=0.73, P<0.001), participants with the lowest (OR(primary vs uncompleted
      primary education)=0.72, P=0.008) and the highest education levels (OR(college or
      higher vs secondary education)=1.26, P=0.022), unemployed participants
      (OR(unemployed vs housekeepers/students)=1.80, P=0.001), and
      administrative/intellectual employees (OR(administrative/intellectual employees
      vs housekeepers/students)=1.75, P=0.001), participants self-classified in the
      lowest social class (OR(labor vs lower)=0.50, P<0.001); residents from urban and
      suburban communities (OR(rural vs suburban/urban residence community)=0.86,
      P=0.037), and participants from the Eastern geographical region of Slovenia
      (OR(Eastern vs Western)=1.12, P=0.097). CONCLUSION: In Slovenia, employed women,
      aged 40-49, with at least college education level were identified as the largest
      population sub-group at very high risk for frequent stress perception with at
      least minor difficulties in coping with these feelings, requiring specific public
      health measures to be introduced in this group.

PMID- 15726690
TI  - Ethical pylons of the health bridge to peace.

PMID- 15726691
TI  - Teamwork and the quality of care.

PMID- 15726692
TI  - [Injury to the pelvic ring. Diagnosis and current possibilities for treatment].
AB  - Pelvic fracture, especially in combination with multiple trauma, can still lead
      to ife-threatening situations. Only clear inclusion criteria and decisions can
      ensure survival of the patient, the key task being mechanical stabilization using
      external fixators or pelvic clamps with or without surgical intervention for
      hemostasis. The basis for problem-orientated management is a precise
      classification, which is based on conventional X-rays in emergency situations and
      detailed analysis of computed tomography for the planning of definitive surgical
      interventions. The classification groups postulated are stable pelvic fractures
      (type A), rotational unstable pelvic fractures (type B -- partial stability of
      the posterior ring present), and translational instabilities (type C -- with a
      complete disruption of the anterior and posterior pelvic ring). This
      classification leads to clear indications for pelvic ring stabilization as
      surgical interventions are only exceptionally indicated in type A fractures,
      stabilization of the anterior ring is sufficient for type B fractures, and
      combined posterior and anterior stabilization is necessary for treatment of type
      C fractures. Following these concepts and by using standardized procedures and
      implants, the high rate of enclosed anatomical healing can be achieved even after
      type C injuries. Nevertheless, the role of concomitant soft tissue injuries and
      scar formation is not clear as the origin of the frequently observed long-term
      clinical impairments even after anatomical reconstruction of the osteoligamentous
      structures.

PMID- 15726693
TI  - Insulin resistance is associated with liver fibrosis in non-diabetic chronic
      hepatitis C patients.
AB  - BACKGROUND/AIMS: Liver steatosis is a frequent finding in chronic hepatitis C. An
      association has been suggested between steatosis and fibrosis progression rate,
      but the pathogenetic mechanisms linking fatty infiltration and collagen
      deposition are unknown. METHODS: We measured the levels of insulin resistance (as
      HOMA score) and leptin in 221 non-diabetic chronic hepatitis C patients, to
      assess their impact on liver steatosis and fibrosis, relative to other factors,
      using a multivariable logistic regression. RESULTS: When all 221 patients were
      considered, steatosis was associated with excessive alcohol intake, genotype 3,
      and serum HCV RNA level, whereas fibrosis was associated with HOMA score and age.
      In 152 patients infected with genotype non-3, steatosis was associated with
      alcohol abuse and HCV RNA level, and fibrosis with HOMA score and age. In the 69
      patients with genotype 3, steatosis and fibrosis were associated with each other.
      The association between fibrosis and HOMA score held also when 22 obese patients
      were excluded from the analysis. Levels of insulin resistance were not correlated
      with the presence of steatosis. CONCLUSIONS: Thus, insulin resistance (but not
      leptin) may play a role in fibrogenesis in chronic hepatitis C patients infected
      with genotype non-3.

PMID- 15726694
TI  - Lithuania's labour limits.

PMID- 15726695
TI  - Depression in post-communist Romania.

PMID- 15726696
TI  - Profile: Alfred Sommer: a life in the field and in the data.

PMID- 15726700
TI  - Antibiotic increases risk of sudden death.

PMID- 15726697
TI  - Hydatid cyst of the cervical region in a child. A rare location.

PMID- 15726701
TI  - Insulin sensitizer affects lipids.

PMID- 15726702
TI  - FDA approves artificial spine disc.

PMID- 15726703
TI  - Treating pain after Vioxx. Should you switch to another COX-2, a traditional non
      steroidal anti-inflammatory, or acetaminophen.

PMID- 15726704
TI  - New hips, knees, and now...ankles. Ankle replacement surgery shows promise,
      particularly in the elderly--but the procedure has room to grow.

PMID- 15726705
TI  - Universal causes of heart attacks. What's bad for your heart is bad for
      everyone's heart.

PMID- 15726706
TI  - Clot-busters plus angioplasty: the new paradigm?

PMID- 15726707
TI  - After a heart attack, don't leave the hospital without aspirin.

PMID- 15726708
TI  - Mild Alzheimer's can cause problems behind the wheel. Restricting driving to
      familiar neighborhoods and eliminating distractions in the vehicle could reduce
      driving error.

PMID- 15726709
TI  - Bad mood, good witness.

PMID- 15726710
TI  - Dreaming may not be the key to good health.

PMID- 15726711
TI  - Assessing glaucoma's risk factors. During initial screening, signs of damage to
      the optic nerve could be more reliable indicators of the disease.

PMID- 15726712
TI  - Even mild kidney disease can cause heart trouble.

PMID- 15726713
TI  - Red meat, wine trigger ulcerative colitis relapse.

PMID- 15726714
TI  - Acupuncture: does it work? The science about this ancient practice is still
      inconclusive, but...

PMID- 15726715
TI  - Put fiber high on your grocery list. A diet full of fruits, vegetables, and whole
      grain foods could help you control your blood sugar.

PMID- 15726716
TI  - Intensive diabetes control results in less nerve damage.

PMID- 15726717
TI  - Soft drinks with sugar increase risk of women developing diabetes.

PMID- 15726718
TI  - MRI detects breast cancer. Despite a greater chance for false positives, the
      method could benefit some women with a genetic mutation.

PMID- 15726719
TI  - I am in my 60s and have been taking Fosamax for osteoporosis. I was recently
      diagnosed with osteo arthritis in my knees. Since Fosamax helps bones, could it
      do something for the bones in my knees?

PMID- 15726720
TI  - I get routine medications from a mail-order pharmacy and emergency prescriptions
      from a drugstore. Who keeps tabs on possible drug interactions?

PMID- 15726721
TI  - The visibility of 350 degrees C black-body radiation by the shrimp Rimicaris
      exoculata and man.
AB  - The eye of the 'eyeless' shrimp Rimicaris exoculata is unusual in having no image
      forming optics and a high concentration of rhodopsin. The shrimps swarm around
      350 degrees C hydrothermal 'black smoker' vents in the Mid-Atlantic Ridge. There
      is no other known source of visible light in the shrimp's environment. The
      spectral sensitivity of rhodopsin is well matched to typical spectra of
      bioluminescence of organisms found at lesser depths, but other animals detect
      such emissions without the unusual features of the R. exoculata eye. These two
      features are most easily understood as an adaptation for the detection of
      extremely faint sources of light. Physical calculations presented here indicate
      that the shrimp could see the black-body radiation of the 350 degrees C vents,
      even though these sources are practically invisible to the human eye. This would
      be useful to the shrimp as it feeds on sulphide-loving bacteria very near to the
      vents but must avoid the lethal 350 degrees C vents themselves.

PMID- 15726722
TI  - Immunopathogenesis of attenuated strain of chicken infectious anemia virus in one
      day-old specific-pathogen-free chicks.
AB  - In the present study, the immunopathogenicity of chicken anemia virus (CAV)
      vaccinal strain was studied in one-day-old specific-pathogen-free (SPF) chicks.
      Hematocrit values, histopathological changes in haemopioetic and lymphoid organs,
      ELISA for CAV antibodies and PCR for CAV genome were used as testing assays for
      the study. Vaccinated chicks showed signs of anemia, lower hematocrit values and
      histopathological lesions in liver in the form of hepatocytes swelling to Centro
      lobular necrosis and apoptosis. Histopathology change in spleen (depletion of
      lymphocytes and apoptosis) and thymus (depletion of thymocytes and apoptosis)
      together with variable degrees of seroconversion rate were observed along the 10
      weeks of the experiment indicating 2 waves of immune response in vaccinated
      chicks compared to the control non-vaccinated group. Detection of CAV-DNA in the
      liver of vaccinated chicks indicated the presence of the virus, when the antibody
      levels were decreased in some chicks. There was a consistent correlation between
      the 4 parameters used. It is concluded that the attenuated CAV vaccine strain
      induces anemia and lesions in the lymphoid organs. The histopathology and PCR are
      useful tools for evaluation and quality assurance of CAV vaccines.

PMID- 15726723
TI  - Cobb Institute named after renowned anthropologist to address disparities.

PMID- 15726724
TI  - Restricting the sale of pseudoephedrine to prevent methamphetamine production.

PMID- 15726725
TI  - [IV Congress of the Russian Society of Gastroenterologists. Plenary reports.
      Abstracts].

PMID- 15726726
TI  - Practice brief. Developing a coding compliance policy document.

PMID- 15726727
TI  - [Patient's card. What kind of exercise should be done to strengthen the bones?].

PMID- 15726728
TI  - Current and lifetime psychiatric illness in women with Turner syndrome.
AB  - Abnormalities in quality of life and cognitive measures have been observed in
      women with Turner syndrome (TS), and a relationship between these phenomena and
      chromosomal constitution has been suggested. In contrast, few studies have
      systematically evaluated the presence of mood and behavioral syndromes in these
      women. In this study, 100 TS women were administered the Structured Clinical
      Interview for DSM IV after a two-week period during which their hormone
      replacement had been discontinued. The majority of women who met criteria for a
      psychiatric condition had a mood or anxiety disorder. Overall, 52 (52%) of the TS
      women met criteria for a current or a past depressive or anxiety disorder.
      Eighteen of the women with TS met criteria for a current Axis I psychiatric
      disorder [Depression--major (n = 5), minor (n = 5), dysthymia (n = 1); Anxiety (n
      = 9)]. Forty-six of the women with TS met criteria for a past Axis I psychiatric
      illness [Depression: unipolar (n = 41), bipolar (n = 3); Anxiety (n= 7); eating
      disorder (n =6); substance dependence (n = 3)]. Five women with TS met criteria
      for an Axis II personality disorder. Women with TS reported a higher rate of
      lifetime depression compared with rates observed in community-based studies but
      similar to those obtained from gynecologic clinic samples.

PMID- 15726729
TI  - Promoting road traffic injuries research in South Asia: capacity strengthening in
      health research.
AB  - Ideally, health policies should be based on valid scientific evidence and such
      evidence requires health research. Health research is also an essential tool for
      achieving equity in health and development. Although the need to carry out health
      research is noe well accepted, South Asia countries still lag behind and do not
      make any meaningful contribution to health research and development, This paucity
      in research work is due to a lack of incentives, shortage of skilled manpower,
      poor exposure and insufficient orientation to the methods and materials of
      biomedical research. Research capacity is a tool to help a country deal with it's
      national health problems in as effective and efficient a manner as possible. It
      is, therefore, part of the national health system ans should be integrated in a
      comprehensive national health plan for the promotion of health and the delivery
      of health services to the country. Capacity strengthening is recognized as a
      crucial step in the process of integrating the use od research doe decision
      making in the health system of a country. This is especially true for conditions
      such as road traffic injuries, which present a new challenge for existing health
      systems.

PMID- 15726730
TI  - Impairment in clock-time estimation following right hemisphere ischemic damage.
AB  - In order to assess clock-time estimation (CTE), we asked "what time is it in your
      opinion?" to 48 recent stroke in-patients, 21 with right (RH), 27 with left
      hemispheric (LH) lesions, and to 20 control in-patients without brain lesions
      (C). Errors were measured in terms of the number of minutes by which the
      estimated clock-time was later (advance errors) or earlier (delay errors) than
      the real clock-time. CTE was considered pathological when exceeding the mean
      advance or delay errors observed in control patients plus 2.5 standard
      deviations. The estimation of the duration of a short psychological interview was
      also assessed. CTE, and not duration estimation, was disturbed in patients. RH
      patients made significantly more pathological advance errors than LH patients
      (43% vs. 12%). This study points out the RH dominance for CTE in stroke patients.

PMID- 15726731
TI  - Health insurance oversight: mandated benefits issue brief: prostate cancer
      screening coverage requirements: year end report--2004.

PMID- 15726732
TI  - Health insurance oversight issue brief: mandated benefits: osteoporosis coverage
      requirements: year end report--2004.

PMID- 15726733
TI  - Health insurance oversight issue brief: mandated benefits: off-label drug
      coverage requirements: year end report--2004.

PMID- 15726734
TI  - Health insurance oversight issue brief: mandated benefits: inpatient mastectomy
      length of stay & breast reconstructive surgery coverage requirements: year end
      report--2004.

PMID- 15726735
TI  - Health insurance oversight issue brief: mandated benefits: infertility treatment
      coverage requirements: year end report--2004.

PMID- 15726736
TI  - Health insurance oversight issue brief: mandated benefits: diabetes coverage
      requirements: year end report--2004.

PMID- 15726737
TI  - Health insurance oversight issue brief: mandated benefits: colorectal cancer
      screening coverage requirements: year end report--2004.

PMID- 15726738
TI  - Health insurance oversight issue brief: mandated benefits: clinical trial
      coverage requirements: year end report--2004.

PMID- 15726739
TI  - Health insurance oversight issue brief: mandated benefits: cervical cancer
      screening coverage requirements: year end report--2004.

PMID- 15726740
TI  - Health insurance oversight issue brief: mandated benefits: breast cancer
      screening coverage requirements: year end report--2004.

PMID- 15726741
TI  - The biology and control of ticks infesting dogs and cats.

PMID- 15726742
TI  - Attitudes toward euthanasia in Hong Kong--a comparison between physicians and the
      general public.
AB  - This article reports the findings of a cross-sectional study that compared the
      attitudes of 618 respondents of a general household survey and a random sample of
      1,197 physicians toward different types of euthanasia in Hong Kong. The general
      public was found to agree with active euthanasia and non-voluntary euthanasia and
      was neutral about passive euthanasia. On the other hand, physicians agreed with
      passive euthanasia, were neutral about non-voluntary euthanasia, and disagreed
      with active euthanasia. Factors affecting the respondents' attitudes were also
      explored. The article ends with policy and research implications of the findings.

PMID- 15726743
TI  - The existential effects of traumatic experiences: a survey of young adults.
AB  - This study examined the relation between exposure to trauma and attitudes toward
      existential issues. Participants were 504 undergraduate students (average age =
      19.67) who answered questions on exposure to trauma, fear of death, overall
      distress, and meaning in life. Results indicated that those with a history of
      trauma exposure had higher levels of overall distress, but there were no
      differences in death anxiety or meaning in life. The results suggest that the
      positive outcomes (less fear of death and increased meaning in life) associated
      with exposure to traumatic events may be relatively rare, especially amongst
      younger adults.

PMID- 15726744
TI  - Are some animals more equal than others?

PMID- 15726745
TI  - Condolence houses in Sanliurfa: fading away of a tradition and a creative attempt
      to preserve it.
AB  - This article reports the results of qualitative research conducted to investigate
      the change in the traditional manner of giving and accepting condolences in
      Sanliurfa, a city with a unique sociocultural structure in the southeastern part
      of Turkey. Our methodology was based on direct observation of behavior and
      detailed, open-ended interviews with participants. This article aims to
      investigate the reasons for moving the condolence tradition from family homes to
      specially built condolence houses a decade ago and discusses the functional
      significance of the ceremonial events in giving and accepting condolences.

PMID- 15726746
TI  - Malone D G, Baldwin N G, Tomecek F J, et al: Complications of cervical spine
      manipulation therapy: 5-year retrospective study in a single-group practice.
      Neurosurg Focus 13 (6):Clinical Pearl, 2002.

PMID- 15726749
TI  - [Discovery of mineralocorticoid hormones].
AB  - In 1855, the clinical and anatomical observations of Thomas Addison brought the
      pathology of the adrenal glands to the attention of his fellow physicians. His
      description had such an impact that Trousseau proposed to call this condition by
      Addison's name. On the basis of experimental finding, Brown-Sequard declared that
      the "adrenal glands play an essential role in the preservation of life". Many
      therapeutic trials were made in vain to slow down the fatal course of the
      disease. The discovery of deoxycorticosterone by T. Reichstein in 1939 ensured
      the survival of patients with Addison's disease. Its treatment greatly improved
      when cortisone became available and could be associated with
      desoxycorticosterone. The Nobel prize for physiology and medicine was awarded to
      the authors of these important discoveries: two biochemists (E.C. Kendall and T.
      Reichstein) for their work on the adrenocortical hormones, and a rheumatologist
      (P.S. Henck) for the therapeutic use of cortisone. In 1955, T. Reichstein
      actively participated in the isolation and the synthesis of aldosterone, a
      powerful mineralocorticoid, the last hormone of the adrenal cortex to be
      discovered.

PMID- 15726750
TI  - Was this the demise of the food critic?

PMID- 15726751
TI  - [Skevos Zervos (1875-1966) and the first transplants of monkey testicles to a
      man. ].
AB  - Professor Skevos Zervos (1875-1966) is esteemed as a great doctor, researcher and
      humanist as well as a benefactor of hippocratism and a greek patriot. Through
      this article we try to elucidate his contribution in the field of testicle
      transplantation where his supremacy is incontestable: indeed he performed the
      first successful testicle transplantation from an ape to a man in 1910. This fact
      was officially recognized by Serge Voronoff (1866-1951) .

PMID- 15726752
TI  - [The strength of the shaman in Brazilian colonial medicine of the XVI and XVIII
      centuries].
AB  - The strategy of the colonial conquest of Brazil by the Portuguese, between the
      XVI and XVIII centuries was linked to the complex set of political, economic and
      military forces from the Metropolis and the Church. In the first contacts with
      the Indian populations, on the coast, the colonizing elements, chiefly, the
      religious ones, perceived the extraordinary importance of the Indian shaman in
      the organizational structure of the autochthonous populations. Thus, the physical
      and moral destruction of the Indian shaman and his substitution by healing
      doctors and priests had become a fundamental part of the plans designed by the
      Metropolis and the Church in consolidating the territorial conquest.

PMID- 15726753
TI  - [The ginseng growing district, taxation and trade in ancient Korea].
AB  - The very first record of ginseng in the Korean peninsula dates back to early 6th
      century A.D., with its concentration in Chinese sources. Regardless of the fact
      that the Korean ginseng was introduced to China before th birth of CHrist, there
      is no writing about it for 500 years. This is because the Chinese substituted
      Korean ginseng for the Chinese one, which was cultivated around the Shangdang
      Area. The ginseng, however, is greatly influenced by natural environment and its
      native area bing Manchurian and the Korean peninsula. It is believed that ginseng
      range from the northern mountains of Pyongando and Hamkyongdo provincnes to the
      southern Taebaek and Sobaek mountains in Korea. Especially the area of
      Madasan(Baekdusan?) mountain was well-known for ginseng-growing district. The
      ginseng taxation of the Three Kingdoms period seems to have gone through certain
      changes along the development stages of the ancient state. The first taxation
      stage is estimated to be in the form of a tribute. Afterwards, as the governing
      power of central government was gradually strengthened in the subjugated places,
      there was a major replacement from tributary form to actual goods levy. The
      actual areas of such tributary collection is unknown, but the Sejongshilok
      Chiriji (geographical records of Sejong chronicles) of the early Choson ear
      indicates 113 prefectures and countries as those which submit ginseng to the
      central government. These administrations provide permissible clues to the
      historic background of ginseng-taxed regions of the Three Kingdoms. The ginseng
      trade also is estimated to have flourished in ancient Korea through the Han
      commanderies of China. However, the writings of Korean ginseng trade is non
      existent until 6th century A.D.. Such phenomenon can be attributed to few
      reasons. First, the Chinese took little interest in Korean ginseng as they
      believed they had their own native ginseng in China. Second, same ignorance
      resulted from its inflowing but new feature. Third, active communication became
      impossible as the Goguryo-China relations deteriorated overall after the closing
      of the commanderies. Nevertheless, ginseng eventually was properly introduced
      into China as the relations between regions improved after the 5th century A.D.,
      which led the Chinese to realize the difference between Chinese and Korean
      ginseng. So it is estimated that such causes generated the real beginning of
      ginseng records in the 6th century. Based on the remaining texts, it can be
      inferred that trade in the Three Kingdoms era usually was conducted in each
      kingdom were all different, which was reflected in their respective contact with
      China. Such characteristics must have directly influenced their ginseng trade
      with China as well. For example, Shilla was only able to perform major ginseng
      commerce with China from the 7th century. There are various records of ginseng
      trade in Unified Shilla period, owing mostly to the previous tributary trade.
      Additionally, there is a case in which a certain individual presented Korean
      ginseng to a Chinese, as well as a case of Shilla ginseng trade in Japan.
      Aforementioned examples clearly illustrate that the fundamental structure of
      ginseng trade in East Asia was completed during the Unified Shilla period.

PMID- 15726754
TI  - [King Injo's disease and burnt needle therapy].
AB  - This paper investigates an interrelationship between burnt needle therapy and
      King Injo's disease. From 1633 (Year 11 in King Injo's reign) to May 5, 1649
      (Year 27 in King Injo's reign), right before his death, King Injo was treated
      with burnt needles by Yi Hyeongik, an acupuncturist when the king had health
      problems. This study arises from two questions: why was King Injo often treated
      with burnt needles? and what effect did burnt needles have?Burnt needle therapy
      is a combined form of acupuncture and moxibustion. Yi Hyeongik was famous for
      eradicating pathogenic factors. He was appointed as a doctor in the Royal
      Hospital. The medical definition for pathogenic factors is that they are disease
      causing factors. Understanding the pathogenic factor for King Injo's disease
      could make it possible to find the interrelationship between burnt needles and
      the king's disease. In the Joseon ear, the prevalent belief about diseases was
      that diseases could be caused by homeopathic magic. Some people thought
      homeopathic magic caused King Injo's disease. The actual reasons for King Injo's
      disease were the participation in the excessive rites of Queen Mother Inmok's
      funeral and the constant oppression from the Ching Dynasty after disgraceful
      defeat in the war. When King Injo started to be sick, homeopathic magic cases
      were found in the royal palace. The king's incurable disease was believed to have
      happened as a result of homeopathic magic. King Injo's suspicion toward Princess
      Jeongmyeong derived from her mother, Queen Mother Inmok. Moral justification for
      King Injo's coup was Gwanghaegun or Prince Gwanghae's immoral conduct toward
      Queen Mothe Inmok. After he was installed, King Injo obeyed the Queen Mother and
      showed her every attention. Meanwhile, he treated Princess Jeongmyeong with
      respect, maximized the moral justification for the coup, and solidified the royal
      authority. However, constant rebellions and treasons threatened King Injo. The
      king suspected that Queen Mother Inmok and Princess Jeongmyeong were involved in
      homeopathic magic cases because both figures could affect major rebellions and
      treasons. Homeopathic magic is a kind of ideological belief and psychological
      suspicion. Accordingly, burnt needle therapy could have an actual effect on
      treating the diseases of the body. It could have a psychological effect in
      treating pathogenic factors as well. As burnt needles were often used for the
      king's disease, remarkable development of acupuncture and moxibustion during the
      King Injo's era was a characteristic in the history of medical science in the
      Joseon Dynasty.

PMID- 15726755
TI  - [A study on the medical care of the royal family in the Chosun period in 1898 -
      as recorded in the Taeuiwon Ilgi].
AB  - Taeuiwon was in charge of the medical care of the royal family in the Chosun
      period of 1898. The Taeuiwon Ilgi is the document which was recorded by Taeuiwon
      officials. In this study, the authors studied the contents of Taeuiwon Ilgi of
      1898 in order to understand the medical care of the royal family of the Chosun
      Kingdom. In 1898, Taeuiwon took some careful measures to take good care of the
      royal family. Taeuiwon physicians made regular inquiry about their health through
      the format called Moonan. The Moonan was to check out the health conditions of
      them. When Taeuiwon carried out Moonan, Emperor Kojong was asked to take a
      medical examination called Ipjin by the court physicians of Taeuiwon, even if he
      were in good condition. Taeuiwon physicians also regularly prescribed
      Insamsokmium when the royal family performed the religious service or went into
      mourning. Insamsokmium is a kind of restorative food containing ginseng. From the
      above, we conclude that Taeuiwon provided the preventative care to them. It was
      considered the proper way to such kind of high personage in that period.

PMID- 15726756
TI  - [A history of the research department of the Severance Union Medical College].
AB  - The Research Department of the Severance Union Medical College was founded on
      November 4th, 1914. Drs. R. G. Mills, J. D. VanBuskirk and A. I. Ludlow were the
      co-founders of the department. The department aimed at investigating the medical
      problems of Koreans which originated from the difference of diet, customs and
      habits. The main fields of the research were divided into three: traditional
      medicine, diet of the Koreans, and special diseases in Korea. As to the research
      of the traditional medicine, Mills conducted extensive investigations on the
      drugs mentioned in the pharmacopeia of the traditional medical texts. His work
      included the translation of the medical texts into English, which unfortunately
      was not published, and the collection of thousands traditional drugs and
      botanical specimens. To the second field, VanBuskirk contributed much. His
      research was mainly focused on investigating the characteristics of Korean diet,
      finding out its problems, and recommending more balanced diet. The third field
      was the research of the diseases specific in Korea. The diseases caused by
      various parasites were the main targets of the research. At first, the Research
      Department was a laboratory where research was actually being carried out. But,
      its nature has been changed as each department became the center of research
      activities. The Research Department became a research promoting center which
      provides research funds for each department or individual researchers. The
      founding of the Research Department of the Severance Union Medical College marks
      a turning point in the history of SUMC in the sense that academic activities
      began to become more important in the missionary institute.

PMID- 15726757
TI  - [Dentistry in Korean during the Japanese occupation].
AB  - The Japanese introduction of dentistry into Korea was for treating the Japanese
      residing in Korea Noda-Oji was the first Japanese dentist for Japanese people in
      Korea in 1893, and Narajaki doyoyo, an invited dentist was posted in the Korean
      headquarter of Japanese army in September, 1905. The imperialist Japan licensed
      the dental technicians (yipchisa) without limit and controlled them generously so
      they could practice dentistry freely. This measure was contrary to that in Japan.
      (In Japan no new dental technician was licensed.) Komori, a dental technician
      opened his laboratory at Chungmuro in 1902. The dental technician had outnumbered
      by 1920. In 1907, the first Korean dental technician Sung-Ryong Choi practiced
      dentistry in Jongno. The imperialist Japan made the regulations for dental
      technicians to set a limit to the advertisement and medical practice of dental
      technicians. The first Korean dentists Suk-Tae Ham was register No. 1 in the
      dentist license. The Kyungsung dental school was established by Nagira Dasoni for
      the purpose of educating some Korean people that contributed to Japanese
      colonization. It made progress with the help of Japan, it was was given the
      approval of the establishment of the professional school in January the 25th,
      1929. It was intended to produce Korean dentists in the first place but became
      the school for Japanese students later on. The association of Chosun dentist,
      which had been founded by Narajaki doyoyo, was managed by Japanese dentists in
      favor of the colonial ruling. The Hansung Association of Dentists established in
      1925 was the organization made by the necessity of the association for Koreans
      only. The Japanese forcefully annexed the Association of Hansung Dentists
      (Koreans only) to the Association of Kyungsung Dentists to avoid collective
      actions of Korean dentists in the name of 'Naesunilche' -- 'Japan and Korea and
      one'. Their invading intention was shown in the event of 'decayed tooth
      preventive day'. Japanese controlled the gold for dental treatment by licensing
      and limited the stuff for dental treatment by rationing. The association of
      Chosun dentists was a group organized for the academic purpose by Nagira Dasoni
      and etc. In October of 191, where as the association of Kyungsung dentists was
      constructed on the background of Nagira Dasoni. This establishment of the
      association of Kyungsung dentists represented a backlash against Ikuda singjo
      having a complete control over the association of Chosun dentists. The number of
      Koreans who wrote to the Chosun Dental Science Academy was 27, and they wrote 75
      articles, which amounted to 15% of 486 articles. The number of Koreans who wrote
      to the Kyungsung Dental Science Academy was 16, and they wrote 52 articles, which
      amounted to 11% of 481 articles. These had been a lot of improvement by activity
      backlash of the dental association. However, they experimented Korean people. The
      experiments included the experimental stimulation of dental pain by Nagira
      Dasoni, use of toxic agents on human bodies such as mercury, bismuth and
      carcinogenic benzole, and experimental treatments with a poor prognosis. Worst of
      all, the rapid discrimination was stressed. The different dentition according to
      races was the subject of comparison researches. The dangerous chemicals were
      sometimes used. The non-akaloid medication was investigated to relieve the dental
      pain but, the habitual side effects were not unusual by the overuse of morphine
      or heroin, which was known to be irrelevant due to their habitual side effect.
      The use of new and unproven material was recommended as well. Especially, the
      alloy that substituted gold, attracting attention, was substantiated by
      researches.

PMID- 15726758
TI  - [Paul D. Choy: A life for learning].
AB  - Paul D. Choy was born on February 26th, 1896. He spent his childhood in Japan and
      America, and he returned to Korea when he turned twenty one years old. He
      graduated from Severance Union Medical College in 1921. After graduating the
      college, he went to Peking Union medical College to study parasitology. He came
      back to Korea after one year as the first parasitologist in Korea. On returning,
      he took the charge of the clinical laboratory of Severance Hospital. Before long
      he made another journey for study to Canada. He spent two years in Toronto
      University studying pathology. After studying pathology, he challenged a new
      field of medicine. It was medical jurisprudence. He stayed two years in Japan in
      order to earn his doctorate in medical jurisprudence in Tohoku Imperial College.
      This time he returned as the first specialist in medical jurisprudence in Korea.
      His field of study was not confined to medical field. He had a deep interest in
      current situation in Manchuria and Mongol, and wrote a book on this matter. His
      interest also extended to the history of ancient Korean people. He made extensive
      studies on this subject, which resulted in publishing a huge work on the origin
      of Korean people and it ancient history. He was a true pioneer of medicine in
      Korea and his life was characterized by endless quest for learning.

PMID- 15726759
TI  - [Medical history in Korean history textbooks].

PMID- 15726760
TI  - [Encounters of the Korean body with the traditional and modern medical systems].
AB  - The body has been an intense focus of attention since the 1990s both in academic
      and mundane discourse. In philosophy, literature critique, sociology and
      anthropology the body has been found to have various implications and auras
      around it.I try to explain the body as the subject of medicine rather
      philosophically, in terms of nature, culture and phenomena. And then I look into
      the Korean body of the late 19th century when western biomedicine was first
      introduced. The Korean body was encountering traditional and modern biomedical
      medicines in three different spaces i.e., corporal, social and moral. The
      corporal space was the space into which direct intervention such as surgery was
      performed. The body was also situated in the social space where imperative social
      measures such as sanitation and sterilization was imposed. The body also had the
      moral space, invasion into which evoked great moral upheaval. It was when the
      government ordered the public to cut the long and bound hair, which had long been
      the symbol of their identity. Reflecting upon the philosophical perspectives and
      examining concrete cases of the encounters of the body with the two medical
      systems, I argue that we should have new perspectives that embodies the
      historical and phenomenological experiences of the body.

PMID- 15726761
TI  - [Philosophical background of evidence-based medicine].
AB  - Through the whole history of medicine, there runs a long struggle between two
      principal tendencies - empiricism and rationalism. The empirical trend lays its
      emphasis on "experience" for the cure of the sick. The rationalistic trend lays
      its main emphasis on "mechanism" for the causes of diseases. The term "evidence
      based (EBM)", defined as "the conscious, explicit and judicious use of the best
      current evidence in making decisions about the individual patients", was
      introduced about ten years ago. The proponents has been described EBM as a
      "paradigm shift" that will change medical practice in the years ahead. But there
      has been considerable debate about the value of EBM. The modern medicine,
      following philosophy of modern science such as the 'realism controlled by
      empiricism', has developed biomedical model. But the EBM wrapped with clinical
      epidemiology and statistics, represents response of empiricism to the rationalism
      (realism). The roots of EBM extend back at least as far as the Paris clinical
      school, and the work of Pierre Louis in Paris in the early 19th century.Is EBM a
      paradigm shift? To answer this question, we have to specify the alternative with
      which we are comparing EBM. The alternative to EBM is the basic science approach:
      studying the pathophysiological mechanism of the body. But EBM is so clearly
      intertwined with and complementary to the basic science that it would make little
      sense to see EBM as a paradigm shift away from basic science. In a sense,
      evidence-based medicine shows only methodological contribution aimed at improving
      the gathering and sorting of the best information published by biomedical
      scientists and clinical epidemiologists for use in clinical practice. Although
      EBM and the traditional medicine embody different approaches, this does not mean
      that they are competitors. In fact, the two approach need each; neither can stand
      alone for the development of clinical practice.

PMID- 15726762
TI  - Consent for organ transplantation and autopsies.
AB  - The Human Tissue Act of 1983 had its origin in the first successful heart
      transplant operation performed by Professor Christiaan Barnard and his team in
      December 1967. Under the new constitution, however, the Act needs to be reviewed,
      because different ethical and legal demands. The Act is in some instances very
      controversial. For instance it is stated in the Act that the eyes of the deceased
      may be removed without the consent of the relatives. Although this may be
      allowable by law, it would be considered to be highly unethical and against the
      constitutional right of the individual. Regulations relating to the general
      control human bodies, the use of tissue, blood and gametes of living person and
      other issues currently covered by the Human Tissue Act will be revised and
      addressed in the proposed National Health Bill.

PMID- 15726763
TI  - The Widmark formula for alcohol quantification.
AB  - In 1932 the Swedish scientist Eric P Widmark developed two formulae commonly used
      for the calculation of the amount of alcohol ingested and for assessing the
      concentration of alcohol at some time prior to the sampling. The most important
      statement in the respect to these calculations is to stress the unreliability and
      inaccuracy of attempting back-calculations in either direction. Only gross
      approximations can be achieved and no pretence at accuracy must be offered.

PMID- 15726764
TI  - A strict solution for the optimal superimposition of protein structures.
      Retraction.

PMID- 15726765
TI  - Kagan receives MacArthur Fellow "Genius" Award.

PMID- 15726766
TI  - Soldano receives "Tribute to Nurses" Award.

PMID- 15726767
TI  - Oman honored with AstraZeneca "Visions of Hope" Award.

PMID- 15726768
TI  - Culture of preimplantation embryos: facts and artifacts.
AB  - Mammalian preimplantation embryos normally develop within the protected
      environment of the female reproductive tract, which virtually precludes studies
      on embryogenesis in situ. Information must therefore be derived from experiments
      on cultured embryos. Consequently, studies on the epigenetic regulation of
      embryogenesis have long been interwoven with efforts to formulate culture media
      capable of sustaining normal development. In this review, comparative information
      on epigenetic regulation of embryo development is discussed, including
      information on energy substrate and amino acid preferences of embryos. Advantages
      of simple versus complex culture media, and of substituting serum albumin or
      synthetic macromolecules for serum, are discussed. Some potential pitfalls of co
      culture are described. Culture appears to induce anomalies in embryo metabolism,
      which may derive from disturbed intracellular pH. Rationales for selecting
      endpoints to evaluate the outcome of experiments are considered, including
      incorporation of timing of embryo development into the analysis. Poor
      experimental design and/or data analysis can detract from or even negate the
      value of data obtained from embryo culture; examples are examined to help correct
      this problem. All of these points are discussed with a view to using data on the
      needs of embryos for making improvements in the design of culture media, so that
      higher yields and increased viability of embryos are achieved.

PMID- 15726769
TI  - Adaptive strategies regulating energy balance in human pregnancy.

PMID- 15726770
TI  - Angiogenic growth factor expression in the uterus.

PMID- 15726771
TI  - CA125 and endometriosis.
AB  - This review covers the literature on CA125 and endometriosis; data on CA125 and
      oncology are not discussed. In normal women, plasma concentrations of CA125 are
      increased slightly at ovulation and significantly during menstruation. Marked
      increases are observed during pregnancy and following peritoneal irritation by
      infection or surgery. These data are consistent with the concept that CA125 in
      normal women is mainly derived from the endometrium and the irritated peritoneum.
      Plasma concentrations of CA125 are markedly elevated in women with cystic ovarian
      endometriosis and/or deeply infiltrating endometriosis, but not, or only
      slightly, in the luteal phase of women with minimal or mild endometriosis. This
      is consistent with the recent concept which considers minimal endometriosis as a
      normal condition occurring intermittently in many women, in contrast with deep
      endometriosis and cystic ovarian endometriosis which are called 'endometriotic
      disease'. Serum CA125 is not a good marker for endometriosis but it is a helpful
      additional parameter to diagnose endometriotic disease in patients with chronic
      pelvic pain. Following treatment of endometriosis, elevated plasma concentrations
      of CA125 could be used as an argument that treatment has been incomplete, or that
      the condition has recurred. Assaying CA125 in peritoneal fluid requires high
      sample dilutions or a modified immunoradiometric assay, and until now, its
      clinical value has been questionable.

PMID- 15726773
TI  - American Cancer Society gives "Trish Greene Quality of Life" Award to article on
      cancer pain control.

PMID- 15726772
TI  - Human follicle-stimulating hormone produced by recombinant DNA technology: a
      review for clinicians.
AB  - Human follicle-stimulating hormone (FSH) is now produced in vitro by recombinant
      DNA technology. FSH being a complex heterodimeric protein, a eukaryotic cell line
      has been selected for expression work (Chinese hamster ovary cells). The
      pharmaceutical preparation of recombinant human FSH (r-FSH) differs from that of
      human menopausal gonadotrophin (HMG) and the first generation of urinary human
      FSH (u-FSH) in terms of (i) source of bulk materials, (ii) purity and specific
      activity, (iii) batch to batch consistency, and (iv) complete absence of
      luteinizing hormone (LH) activity. Pharmacokinetic characterization of r-FSH has
      shown an absolute bioavailability of approximately 75% after both s.c. and i.m.
      administration and an apparent terminal half-life of 37 +/- 25 h. These
      characteristics are very similar to those of u-FSH. Clinical efficacy and safety
      are currently demonstrated through several randomized, well controlled studies,
      comparing r-FSH administered s.c. with u-FSH administered i.m. for stimulating
      follicular development prior to assisted reproduction treatment and in World
      Health Organization (WHO) group II anovulation. To date, approximately 1000
      patients have been treated with r-FSH. Moreover, r-FSH has recently been used
      successfully in association with recombinant human LH for inducing ovulation and
      pregnancy in WHO group I anovulatory patients. At this stage of r-FSH preparation
      assessment, it is likely that r-FSH will replace all urinary-derived FSH
      preparations for stimulating ovarian follicular development. For clinicians,
      current experience with r-FSH indicates that it should be used with the regimes
      and doses applied to u-FSH.

PMID- 15726774
TI  - Trends, priorities and policy directions in the control of vector-borne diseases
      in urban environments.
AB  - The habitats available in urban environments tend to be rather lacking in
      diversity compared to those in the countryside, and relatively few species are
      able to exploit them. Those that can, however, often find themselves relatively
      well provided with food and places to live, and relatively free of competitors
      and predators. This applies not only to such well-known species as the house
      sparrow, but also to most of the important mosquito vectors of human disease in
      urban areas. Human city dwellers thus tend to be exposed to a different spectrum
      of disease than their rural counterparts. This review describes how the physical
      and social changes associated with urbanization have altered the transmission of
      vector-borne disease. It concentrates on the important mosquito-borne infections:
      malaria, dengue and filariasis. Dengue virus vectors breed in relatively clean
      water in man-made containers, while urban filariasis vectors breed in highly
      polluted water, and these mosquitoes have now been spread by man's activities to
      almost every tropical city. With important exceptions, anopheline malaria vectors
      have not generally succeeded in adapting to urban life, but malaria can still be
      a problem where there are rural pockets in the middle of town. Each of these
      problems requires control using different technologies and timing. The following
      policy implications are stressed. The areas of responsibility between different
      sectors of the local services (health, water supply, sanitation), and between
      these and the public, need to be clearly defined. Due to the biological
      complexities of vector-borne disease, decentralized primary health care systems
      are generally incapable of ensuring that control efforts are adequately targeted
      in time and space. Community support is essential but specialized technical
      skills are also required.

PMID- 15726775
TI  - Bangladesh pharmaceutical policy and politics.
AB  - An analysis of the politics of Bangladesh pharmaceutical policy in the 1980s
      shows how significant health policy reforms in developing countries depend on
      political conditions both inside and outside the country. Bangladesh's drug
      policy of 1982 illustrates that governments can sometimes change public policy in
      ways unfavourable to multinational corporations, while the failed health policy
      reform of 1990 shows that reforms unfavourable to powerful domestic interest
      groups can be more difficult to achieve, even contributing to a government's
      downfall. The case provides evidence of basic changes in how the international
      agenda for health policy is set, especially the growing role of non-governmental
      organizations in international agencies and national policy debates.
      Understanding the political patterns of policy reform in Bangladesh has important
      implications for strategies to affect health policy in developing countries.

PMID- 15726776
TI  - The socioeconomic impact of malaria in Colombia and Ecuador.
AB  - In-depth studies in three communities of Colombia and Ecuador, over a period of
      two to three months in each, were the basis of the economic analysis presented in
      this paper. In Santa Cruz, located at the rio Naya in Colombia, the average cost
      per case of malaria was US$17.30 (indirect costs US$15.80 and direct costs
      US$1.50); the loss corresponded to 20.1% of a minimum monthly wage (1986) or to a
      value of 5.6 days' work. In Perla de Sade, in the Cant6n Quininde of Ecuador, the
      average cost per case of malaria amounted to US$10.40 (indirect costs US$5.90 and
      direct costs US$4.50); the losses corresponded to 20.8% of a minimum monthly wage
      (1989) and to a value of 5.7 days' work. In Calder6n in the Cant6n of San Lorenzo
      in Ecuador, the average cost per case of malaria was US$4.80 (indirect costs
      US$3.50 and direct costs US$1.30); the losses corresponded to 16.0% of a minimum
      monthly wage (1991) with a value of 4.4 days' work. The results in these three
      communities, and in four additional ones, showed that the major economic impact
      of malaria is in the reduction of the labour force of families (indirect costs),
      and less so in the direct costs of care and cure. This emphasizes the economic
      importance of malaria because the rural familes with economies at subsistence
      level depend for survival particularly upon the maintenance of their labour
      force.

PMID- 15726777
TI  - Monitoring of primary health care services: an example from western Uganda.
AB  - Results from baseline and follow-up surveys of the Basic Health Services Program
      in Kabarole District, Western Uganda carried out in 1989 and 1991 are presented.
      Indicators in relation to management capability, infrastructure, levels of basic
      knowledge and skills of health staff, community involvement and utilization of
      health services were measured. Subjectivity of the data collection was minimized
      through use of a randomized study design, and external supervision. Comparability
      of results between the two surveys was assured by employing the same rapid
      assessment methodology, using a fixed set of indicators. The results suggest a
      marked improvement of the health services in Kabarole district since
      implementation of specific project activities and in direct response to action
      taken following review of information from the original survey work. Overall, it
      is felt that this particular method of project monitoring, and using the specific
      method, Systems' Analysis, generates data particularly useful to national
      governments and other health organizations.

PMID- 15726778
TI  - National health information systems in the Pacific islands: in search of a
      future.
AB  - Health information is essential for proper management and deployment of limited
      resources in the health services of the Pacific Islands. There have been numerous
      efforts to establish and strengthen sustainable information systems but the
      common feature of these attempts has been the very limited achievement.
      Subsequently, the use of information as a management tool has been abandoned in
      favour of 'gut feeling', hearsay and adhocry. In the last decade health planning
      and primary health care activities have necessitated the re-emphasis of
      monitoring and surveillance of health and health service indicators. Therefore a
      revival of interest in health information systems is taking place. A review of
      national health information systems in the Pacific showed that routinely
      collected data remained largely untouched by human thought. The contributing
      factors to the current inertia are examined with suggestions on how to elevate
      health information from its current lowly status to its rightful place as an
      essential tool for management. The special problems of small island states, like
      limited resources, geographical isolation, natural barriers to technology, and
      diverse cultural milieu, will be examined in relation to an appropriate health
      information system for Pacific Island countries in the twenty-first century.

PMID- 15726779
TI  - The role of information in the planning, management and evaluation of community
      nutrition programmes.
AB  - Protein-energy malnutrition has many diverse location-specific causes which make
      if difficult to solve through uniform interventions implemented through vertical
      programmes. This paper investigates the role of information in the planning,
      management and evaluation of several community nutrition programmes judged to be
      successful. The programmes come from Tanzania (Iringa), India (Tamil Nadu),
      Dominican Republic and Colombia. The review finds that the initial
      conceptualization and design of these programmes benefited from the results of
      earlier surveys and experience with similar programmes in the same or other
      countries. Strong capacity for operations research is important to assist with a
      myriad of small but important programme design details and larger mid-term re
      orientations. The impact of this information depends upon the flexibility of the
      programme and receptivity of its management towards a learning-by-doing approach.
      Information for on-going programme management differs widely and conforms to the
      overall character of the individual programme. Thus, Iringa employs a simple
      system based on community growth monitoring, primarily to catalyze intervention
      planning and action at household and community levels. Tamil Nadu's system is far
      more complex and is primarily intended to assist in the delivery of centrally
      planned interventions. Programme evaluation benefited from information generated
      within the programme, but more rigorous impact evaluation requires stronger
      designs and more in-depth analysis than is usually provided. Overall, the review
      suggests that characteristics like community participation, empowerment and
      growth monitoring are less important in the short/medium term than strong
      management, a learning-by-doing approach, and the existence of some method for
      informing programme design and management about community needs and responses to
      the programme. The former characteristics may well be important for the longer
      term sustainability of programmes.

PMID- 15726780
TI  - The elasticity of demand for health care in Burkina Faso: differences across age
      and income groups.
AB  - Like many other developing countries, Burkina Faso has been exploring how
      community resources can be tapped to co-finance health services. Although revenue
      generation is important for the viability of health services, effects on
      utilization and on equity of access to health care must also be considered. The
      authors present a logistic regression model to derive price elasticities of
      demand for health care based on cross-sectional survey data. While demand for
      health care appears inelastic overall (-0.79), subgroup analysis reveals
      differences in elasticity across age and income groups. Elasticities of demand
      for infants and children (-3.6 and -1.7) and for the lowest income quartile (
      1.4) are substantially greater than overall elasticity. The method used is
      unusual in that it allows estimation of elasticities before the introduction of
      user fees. This increases the value of the information to policy makers.

PMID- 15726781
TI  - Community financing of drug supplies in rural Nepal: evaluating a 'fee per item'
      drug scheme.
AB  - A new programme in rural Nepal was evaluated in which users partly fund the
      supply of additional drugs needed at health posts. Patients are charged a fee per
      item prescribed (FPI scheme). The scheme is administered by the District Public
      Health Office (DPHO). This scheme is compared with two established schemes: one
      charges patients a fee per prescription ('fee-per-script' or FPS scheme) and is
      administered by independently paid NGO (non-governmental organization) staff; the
      other uses local shops as a means of supplying drugs. The new scheme was
      associated with a rise in average daily attendance from nine to thirty-two
      patients a day (a 240% increase) when compared to a similar period the previous
      year. Fewer drugs were prescribed in the FPI scheme (average per patient 1.8 vs.
      2.4, Chi square P <0.001). The average cost of a drug from the user's perspective
      was approximately 12% lower in the FPI scheme. These factors combined to make the
      average cost to the patient of a prescription half that of one in the FPS scheme.
      The new scheme was 24% cheaper to run on a 'cost per patient' basis when compared
      with the FPS scheme. However, the overall subsidy needed for the scheme to
      operate was higher because of the big increase in attendance. One-off stocktakes
      of ten essential drugs were used to assess the availability of drugs for patient
      use. The proportion of these drugs that were in low supply or absent was 24% in
      the FPI scheme. This was similar in the other two schemes. The government DPHO
      did not perform all the administrative tasks required. These tasks need to be
      simplified and different methods for involving DPHO staff in drug scheme
      management need to be explored. The rapid turnover of senior staff, however, will
      remain a major impediment. This preliminary evaluation shows that an FPI scheme
      promotes a more rational use of resources, compared to an FPS scheme.
      Administration of the scheme may, however, prove to be more difficult. A simple
      field-based comparative assessment of drug supply schemes can give a valuable
      insight into the strengths and weaknesses of a new programme.

PMID- 15726782
TI  - Access policies and utilization patterns in prenatal and child delivery care in
      Mexico.
AB  - In Mexico, people utilize public, private and traditional health providers
      interchangeably and in contrast to official access policies. Access policies for
      prenatal and child delivery services are evaluated using data from the National
      Health Survey of 1988. The study documents significant coverage gaps on the part
      of public providers with respect to their potential coverage, and especially,
      large cross-utilization of social security, Ministry of Health and private
      providers by beneficiaries. Child deliveries in Mexico are attended by a
      physician in only 66% of cases. The percentages are 85% for social security
      affiliates, 53% for women within reach of IMSS-Solidarity services (a relief
      programme for the rural poor) and only 31% for women with official access to
      private or Ministry of Health care, or beyond the reach of services. Seventy
      eight per cent of medical deliveries by women affiliated to social security occur
      at their pre-paid facilities, while 14% deliver at extra cost with private
      physicians, contributing to 32% of deliveries so offered. Even though only 7% of
      insured women deliver at Ministry of Health facilities, this amounts to 20% of
      the Ministry's relief offer. In all, only 66% of affiliates use social security
      delivery services. On the other hand, 36% of deliveries by non-insured women are
      cared for by Ministry of Health providers, and 39% by the private sector; 22% of
      such deliveries occur in social security institutions, amounting to 18% of these
      institutions' care offer. These results indicate a wide departure between policy
      and fact, and the working of distributive and redistributive forces that impinge
      on the quality and efficiency of health care. Open access to the reproductive
      health services of all public institutions, with coordination among them and
      private providers, is suggested as a possible solution.

PMID- 15726784
TI  - Stepping stones--reflections on careers in health.

PMID- 15726783
TI  - Acute respiratory infections: a study on case management in Basrah health
      centres.
AB  - This paper reports the results of a study carried out in Basrah during 1992 on
      the pattern of case management as a control measure of acute respiratory
      infection among children aged under five years. The study involved a detailed
      observation of cases attending 12 health centres in Basrah city and its suburbs.
      A total of 392 cases were included. The cases were almost equally distributed
      according to sex, a fact which may reflect that acute respiratory infections do
      not discriminate between sexes and that our society pays the same attention for
      males and females when they fall ill. Regarding severity, most of the cases were
      mild or moderate, only 5% were severe. The doctors were generally competent to
      handle cases of acute respiratory infection but they had a tendency to
      overprescribe antibiotics. They were very good in excluding non-severe cases but
      they tended to miss some severe cases. The implications of these findings were
      discussed and it was recommended that further specific studies be carried out.

PMID- 15726785
TI  - The UNFPA: twenty-five years and beyond.

PMID- 15726786
TI  - Immunohistochemical localization of lysosomal cathepsin D in schwannomas.
AB  - The immunohistochemical localization of cathepsin D (CD) was demonstrated for the
      first time in 54 schwannomas (32 intra- and 22 extracranial; 47 benign and 7
      malignant) and 5 normal nerve fibers. Granular or vesicular CD-reactive
      structures were observed in all normal Schwann cells. All tumors contained CD
      reactive tumor cells, although the population of CD-reactive tumor cells, the
      density, intracellular localization, and morphology of CD-reactive structures,
      and the intensity of CD immunoreactivity varied from case to case, portion to
      portion, and cell to cell, differing variously from those in normal Schwann
      cells. The variations were greater in malignant than in benign schwannomas. In
      mildly degenerate tumor cells, CD immunoreactivity was increased, possibly in
      response to the increased intracellular degenerate proteins, suggesting that the
      mechanism of induction of lysosomal proteases preserved in normal cells is not
      affected by the process of neoplastic transformation. In lesions of severe
      degeneration or necrosis, CD immunoreactivity was lost in most tumor cells but
      was strong in macrophages invading the lesions and perivascular regions. CD
      immunoreactivity was observed at various intensities in tumor cells in the Antoni
      type A area but not in most tumor cells in the Antoni type B area, suggesting
      that Antoni type B lesions show degenerative changes. The presence of CD-reactive
      tumor cells in all tumors examined and strong CD immunoreactivity observed at the
      invasion front of tumors in some cases of benign or malignant schwannoma suggests
      the possible role of CD in tumor invasion in some cases.

PMID- 15726787
TI  - Clinical and biological considerations regarding glioma based on the TUNEL method
      and immunohistochemical staining using apoptosis-related antibodies.
AB  - We examined 36 gliomas both by the terminal deoxynucleotidyl transferase-mediated
      dUTP-digoxigenin nick-end-labeling (TUNEL) technique and by immunostaining of
      antibodies against apoptosis-related antigens. The apoptotic index (AI) obtained
      by the TUNEL method was 10.77 +/- 3.78% in astrocytomas, 6.19 +/- 1.81% in
      anaplastic astrocytomas, and 5.21 +/- 1.14% in glioblastomas. The AI of anti-Fas
      antibody and Le(Y) antibody in gliomas also showed a similar tendency as the
      results with the TUNEL method. As a result, statistically significant differences
      were observed in the distribution of survival between the two groups according to
      the AI obtained by the TUNEL method. Therefore, an analysis of the AI is
      considered to be useful for prognosis.

PMID- 15726788
TI  - Cytogenetic abnormalities related to histopathologic grade of astrocytic tumors.
AB  - Cytogenetic analysis was performed on 7 low-grade astrocytomas, 10 anaplastic
      astrocytomas, and 14 glioblastomas. Abnormal chromosome numbers were noted in all
      cases of high-grade astrocytomas but were rarely noted in low-grade astrocytomas
      (28%). The most consistent changes in high-grade astrocytomas were complete loss
      of chromosome 10 (61%), gain of chromosome 7 (56%), and loss of chromosome 17
      (28%). Certain structural abnormalities, such as marker chromosomes and double
      minutes (33%), and the deletion and translocation of chromosomes 1 (33%) and 17
      (17%), were also noted. These results indicate that changes in the number and/or
      structure of chromosomes with related inactivation of tumor suppressor gene or
      oncogene activation might play a critical role in the formation and anaplastic
      progression of astrocytic tumors.

PMID- 15726789
TI  - Epithelial differentiation in intraspinal meningiomas.
AB  - To investigate the epithelial features of intraspinal meningiomas, 25 intraspinal
      meningiomas and 25 intracranial meningiomas were examined for the presence of
      pseudopsammoma bodies with hematoxylin-eosin and periodic acid-Schiff staining.
      In addition, we investigated the expression of keratin and epithelial membrane
      antigen (EMA) by immunohistochemical methods. Pseudopsammoma bodies were found in
      3 of 25 cases of intracranial meningiomas (12%), but no definitive pseudopsammoma
      bodies were observed the intraspinal meningiomas. Three cases (12%) of
      intraspinal meningiomas and 9 cases (36%) of intracranial meningiomas, including
      3 cases with pseudopsammoma bodies, were immunoreactive for keratin. All 25
      (100%) intracranial meningiomas and 20 of 25 (84%) intraspinal meningiomas were
      reactive for EMA. In the intraspinal meningiomas, 4 of 25 cases (16%) showed no
      reactivity for EMA. These findings suggest that the origin of certain cell
      components of meningiomas may be different according to the site of the tumor or
      that the nature of meningioma may be modified by the local environment.

PMID- 15726790
TI  - Messenger RNA fingerprinting analysis using arbitrarily primed PCR (RAP) of genes
      expressed during rat C6 glioma cell differentiation.
AB  - To identify differentially expressed genes involved in rat C6 glioma cell
      differentiation induced by cyclic AMP, we adopted mRNA fingerprinting using
      arbitrarily primed polymerase chain reaction (PCR) (RAP). Four complementary DNA
      (cDNA) fragments differentially expressed during differentiation were isolated,
      and they appeared to contain coding regions of corresponding mRNAs. RAP can be
      used to efficiently identify cDNA fragments by comparing nucleotide and deduced
      amino acid sequences with those in databases, and is thus a useful method to
      search for and identify important genes involved in complex cellular processes
      such as glioma cell differentiation.

PMID- 15726791
TI  - Detection of SV40 T antigen genome in human gliomas.
AB  - The monkey polyomavirus simian virus 40 (SV40) has been reported to be associated
      with tumorigenesis of human neoplasms, mainly brain tumors. However, it remains
      controversial whether the virus really exists in human neoplasms and how the
      virus transforms human cells in vivo. We investigated the presence of SV40 T
      antigen genome in 33 human glioma tissue specimens from Japanese patients with
      different histopathologies by means of the polymerase chain reaction (PCR)
      followed by Southern blotting. The SV40 T antigen genome was amplified in 4 of
      the 13 ependymomas (31%) and 3 of the 20 other histotypes of gliomas (15%),
      whereas in the 22 nontumoral brain tissue specimens, only one case was found to
      be positive. DNA sequencing confirmed the PCR products to be those of SV40 T
      antigen. The findings thus suggest that the SV40 genome appears to exist in a
      certain population of brain tumors from Japanese patients, and that it may also
      play a role in the oncogenicity or maintenance of the transformed state.

PMID- 15726792
TI  - An information system to support collaborative brain-tumor research.
AB  - We have developed and are currently maintaining a Neuro-Oncology Information
      System (NOIS) to support brain-tumor research. The system has been adopted for
      use by a group of researchers at several centers in the U.S.A. who are
      collaborating to input, store, and retrieve information concerning tissue
      specimens, corresponding clinical and diagnostic information, and eventual
      research results. The information system consists of a database and user
      interface components. The database has clinical, diagnostic and tissue-inventory
      subsystems, the user interfaces allow for input and query functions on the
      database.

PMID- 15726793
TI  - Primary leptomeningeal meningiomatosis with widespread whorl formation.
AB  - We report a 10-year-old girl with a primary leptomeningeal tumor. She presented
      with a 5-week history of increased intracranial pressure, progressive cranial
      nerve deficits, and spinal compression signs. She had previously had a granulosa
      cell tumor, a benign estrogen-producing ovarian tumor, which was resected 6
      months before the initial neurological symptoms developed. At autopsy, the brain
      and spinal cord showed diffuse neoplastic involvement of the leptomeninges. The
      tumor was composed of small cells with a high nucleus/cytoplasm ratio, which were
      immunoreactive for vimentin but not for epithelial membrane antigen or
      cytokeratin. In addition, the tumor contained many small cellular whorls with
      desmosome-like junctional complexes between the cells, suggesting that the tumor
      was a meningioma, basically of the meningothelial type. The term "meningeal
      meningiomatosis" has been used synonymously with "primary meningeal
      sarcomatosis." The present tumor was considered to be a rare example of
      "meningeal meningiomatosis" of true meningothelial cell origin.

PMID- 15726795
TI  - Stemming the tide: AAED's new esthetic and restorative update.

PMID- 15726796
TI  - Dentin bonding.

PMID- 15726794
TI  - Cervical cord ependymoma with numerous microrosettes.
AB  - "Microrosette ependymoma," which is ependymoma with numerous microrosettes
      throughout the tumor, has rarely been reported. We describe an autopsy case of
      cervical cord ependymoma with two unusual features: the presence of numerous
      microrosettes and the formation of trabecular architecture. The tumor originated
      in the C2 segment of a man aged 23 years and gradually expanded over the
      following 15 years and 10 months until the entire cervical cord was involved.
      Beside the low grade of malignancy, the tumor cells exhibited a strong tendency
      to form microrosettes and trabecular architecture, which formed many perivascular
      pseudorosettes. The microrosettes mostly consisted of only two or a few more
      cells, in the absence of large rosettes. Thus the constituent cells were those
      forming perivascular pseudorosettes. Electron microscopy and immunohistochemistry
      characterized the ependymal properties of the microrosettes, whose lumina
      frequently contained fibril bundles similar to those of the Reissner's fiber
      fibrils, in addition to cilia and microvilli. The pathogenesis of the occurrence
      of numerous microrosettes is unknown; however, a defect in the mechanism of
      regulation of rosette formation and enlargement is the most likely explanation.

PMID- 15726797
TI  - Use of a modified ovate pontic in areas of ridge defects: a report of two cases.
AB  - A modified design for ovate pontics is proposed to achieve the esthetic,
      functional, and hygienic requirements for fixed partial dentures. This design
      should aid the clinician in preparing the edentulous area, thus resulting in less
      discomfort for the patient because little to no ridge augmentation is required.
      The same emergence profile can be developed as with the classic ovate pontic
      design. CLINICAL SIGNIFICANCE: A modified ovate pontic has the following
      advantages: excellent esthetics because it produces a correct emergence profile;
      fulfilled functional requirements; greater ease of cleaning as compared with the
      ovate pontic; an effective air seal, which eliminates air or saliva leakage; the
      appearance of a free gingival margin and interdental papilla; elimination or
      minimization of the "black triangle" between the teeth; and little or no ridge
      augmentation required prior to the final restoration.

PMID- 15726798
TI  - Effect of bleaching and repolishing procedures on coffee and tea stain removal
      from three anterior composite veneering materials.
AB  - Discolored teeth can be treated with resin veneers, but their color changes when
      confronted with staining solutions. Polishing procedures can provide a remedy for
      highly stained composites, but they tend to remove some materials as well.
      However, bleaching procedures are an effective, nondestructive method for solving
      the problem. The aim of this study was to compare the color change of three
      veneer composites exposed to staining solutions and to evaluate the effectiveness
      of a 15% hydrogen peroxide bleaching agent and three polishing systems to remove
      the stain. Forty-five disks (12 x 2 mm) each of Clearfil ST (Kuraray Co. Ltd.,
      Osaka, Japan), Esthet-X (Dentsply/Caulk, Milford DE, USA), and Filtek A110 (3M
      ESPE, St. Paul, MN, USA) were prepared. The specimens were polished with Sof-Lex
      (3M ESPE), Enhance (Dentsply/Caulk), or PoGo (Dentsply/Caulk). Five specimens for
      each material-polishing system combination were immersed in coffee (Nescafe
      Classic, Nestle SA, Vevey, Switzerland) or tea (Earl Grey, Lipton, Blackfriars
      London, England) for 7 days. The remaining disks were stored in water. Color
      measurements were made with a spectrophotometer (X-Rite Seroice SP78, Loaner,
      Koln, Germany) at baseline; after 1, 3, 5, and 7 days; and after bleaching and
      repolishing. After 1 week, one side of the specimens was bleached with Illumine
      office (Dentsply De Trey GmbH, Konstanz, Germany) for 1 hour, and the other side
      was repolished for 30 seconds. All comparisons of color change for the polishing
      systems, times, and staining solutions were subjected to repeated measurements of
      analysis of variance. Paired t-test was used to examine whether significant color
      differences (deltaE*) occurred during immersion at the specified time intervals
      (p < or = .05). Filtek A110 was the least stained resin composite. Its color
      remained under a deltaE* value of 2 during the study. Clearfil ST exhibited the
      most color change after 1 week. All specimens polished with Enhance showed less
      staining, whereas those polished with the Sof-Lex system demonstrated the most
      color change. Water did not cause a variance in the deltaE*. There was no
      difference in the staining potential of coffee and tea. Bleaching and repolishing
      were effective in removing the stains. The resin composites tested reversed
      nearly to baseline color with the bleaching and to less than values at 1 day of
      staining with repolishing. The coffee and tea brands tested stained the
      composites used in this study equally. In-office bleaching was found to be more
      effective than repolishing in the restitution of the color. CLINICAL
      SIGNIFICANCE: The results of this study suggest that the discoloration of resin
      veneers can be partially removed by in-office bleaching and repolishing
      procedures.

PMID- 15726799
TI  - Wear resistance of packable resin composites after simulated toothbrushing test.
AB  - PURPOSE: The purpose of this study was to determine the wear resistance of five
      different packable composites versus two different composite controls using a
      laboratory toothbrushing simulation test. MATERIALS AND METHODS: Twelve samples
      measuring 5 mm in diameter and 3 mm thick were prepared from the following resin
      composites: Packable resin composites SureFil (Dentsply Ind. Com. Ltda,
      Petropolis, Rio de Janeiro, Brazil), Alert (Jeneric Pentron Incorporated,
      Wallingford, CT, USA), Filtek P60 (3M ESPE Dental Products, St. Paul, MN, USA),
      Prodigy Condensable (sds Kerr, Orange CA, USA), Solitaire (Heraeus Kulzer GmbH,
      Wehrheim, Germany), and control resin composites Z100 Restorative (3M ESPE) and
      Silux Plus (3M ESPE). Finishing and polishing were conducted with Sof-Lex disks
      (3M ESPE), and baseline weight (grams) and surface roughness (measured with
      Hommel Tester T 1000, Hommelwerke, GmbH, Alte Tuttinger Strebe 20. D-7730 VS
      Schwenningen, Germany) were recorded. Specimens were aged for 2 weeks until they
      reached a weight that remained constant for 5 consecutive days, and then were
      subjected to 100,000 cycles of brushing (representative of 4.2 yr) using a
      toothbrushing testing machine. Toothbrush heads with soft bristle tips (Colgate
      Classic, Colgate-Palmolive Co., Osasco, Sao Paulo, Brazil) with dentifrice
      suspension (Colgate MFP, Colgate-Palmolive Co.) in deionized water were used
      under a 200 g load. Changes in weight and surface roughness were determined after
      toothbrushing cycles. RESULTS: Significant differences of weight loss and surface
      roughness were found (paired t-test, p < .05). Weight loss percentage (mean [SD])
      ranged from 0.38 to 1.69% (analysis of variance and Tukey's least significant
      difference, p < .05); the weight loss of the materials ranked from least to most
      as follows: SureFil (0.38 [0.56]), Alert (0.52 [0.18]), Z100 (1.16 [0.27]),
      Filtek P60 (1.31 [0.17]), Solitaire (1.51 [0.45]), Prodigy Condensable (1.55
      [0.471), and Silux Plus (1.69 [0.66]). Regarding surface roughness, Prodigy
      Condensable (0.19 [0.08]), Solitaire (0.28 [0.06]), and Z100 (0.30 [0.07]) became
      less rough after toothbrushing, whereas all the others were rendered rougher:
      Alert (0.49 [0.29]), Filtek P60 (0.28 [0.08]), Silux Plus (0.39 [0.091), and
      SureFil (0.81 [0.32]). CONCLUSION: SureFil and Alert were statistically more
      resistant to wear (less weight loss) than were the other materials. SureFil
      became significantly rougher than did all the others. CLINICAL SIGNIFICANCE:
      Overal, packable resin composites are unlikely to show superior wear resistance
      with regard to weight loss and surface roughness compared with current resin
      composites also indicated for posterior restorations.

PMID- 15726800
TI  - Oxygen-inhibited layer in adhesion dentistry.
AB  - PURPOSE: Characteristics of the oxygen-inhibited layer, including bond strength,
      photoinitiator decomposition, and post-curing degree of conversion, were
      investigated. MATERIALS AND METHODS: To investigate shear bond strength, BisCover
      (Bisco, Inc., Schaumburg, IL, USA) and D/E Resin (Bisco, Inc.) were placed on
      disks of Renew composite (Bisco, Inc.) and cured both with and without an oxygen
      inhibited layer. Light-Bond composite (Reliance Orthodontic, Itasca, IL, USA) was
      placed in a gelatin capsule and light cured over the cured resin. After soaking
      in water for 2 hours at 37 degrees C, specimens were sheared to failure using a
      universal testing machine (Model 4466, Instron Inc., Canton, MA, USA). To
      investigate microtensile bond strength, composite substrates prepared using Renew
      A2 composite were light cured either in air or under nitrogen. Light-Core (Bisco,
      Inc.) was placed on each substrate and light cured. The resulting specimens were
      sectioned into composite beams and stressed to failure using a microtensile
      tester (built by Bisco, Inc.). To determine camphorquinone (CQ) decomposition, an
      experimental CQ resin was placed between two glass plates and irradiated for
      different time intervals. The absorption spectrum was obtained using a Cary 50
      Bio UV-Visible Spectrometer (Varian, Mulgrave, Australia). To explore the degree
      of conversion, polyester film strips (Mylar, DuPont, Wilmington, DE, USA) coated
      with the CQ resin were pre-cured in air for different time periods, and then post
      cured at low intensity for 5 minutes under nitrogen. A Spectrum 1000FTIR
      Spectrometer (Perkin Elmer, Norwalk, CT, USA) was used to measure the degree of
      conversion. RESULTS: Bond strength tests resulted in no significant difference
      between samples with or without an oxygen-inhibited layer. The oxygen-inhibited
      layer contained reduced amounts of photoinitiator. The degree of conversion of
      post-cured oxygen-inhibited layers was lower than that for the control.
      CONCLUSION: An oxygen-inhibited layer is not necessary for bonding with composite
      resin. CLINICAL SIGNIFICANCE: It was believed that an oxygen-inhibited layer was
      required for bonding of composite resin. Studies show that composites bond even
      in the absence of an oxygen-inhibited layer, including recent products that cure
      without an oxygen-inhibited layer. With many simplified adhesives, especially
      self-etching, all-in-one adhesives, the oxygen-inhibited layer is acidic. This
      acidity interferes with self-curing reactions, making these adhesives
      incompatible with self-cured composites.

PMID- 15726801
TI  - Critical appraisal. Resin bond to dental ceramics, Part II: high-strength
      ceramics.

PMID- 15726804
TI  - Periodontal splinting.

PMID- 15726805
TI  - Nonmuscle caldesmon: its distribution and involvement in various cellular
      processes. Review article.
AB  - Smooth muscle caldesmon is a thin-filament constituent which takes part in the
      Ca2+-dependent regulation of actomyosin motor activity which converts chemical
      energy of ATP into force. The molecular anatomy of its counterpart found in a
      variety of nonmuscle cells is similar. Both contain about 20 nm long terminal
      domains responsible for functionally important multisite interactions with
      filamentous actin, tropomyosin, Ca2+/calmodulin, and myosin and differ by a 35 nm
      long central, alpha-helical fragment which is lacking in nonmuscle caldesmon. The
      different structural organisation of nonmuscle cells and thus distinct
      distribution of caldesmon implicates its different physiological functions. Due
      to direct interaction with globular and filamentous actin as well as with
      tropomyosin, nonmuscle caldesmon is involved in the assembly, dynamics, or
      stability of microfilaments, whereas the indirect inhibitory effect on
      interaction of the microfilaments with myosin causes its participation in the
      regulation of cell contraction and intracellular motional processes. These
      functions of nonmuscle caldesmon of vertebrates are controlled by Ca2+/calmodulin
      (or other Ca2+-binding proteins) or caldesmon phosphorylation catalysed by
      various protein kinases. Examples of nonmuscle caldesmon involvement in functions
      of higher and lower eukaryote, animal and plant cells are presented.

PMID- 15726806
TI  - Evolutionarily conserved modules in actin nucleation: lessons from Dictyostelium
      discoideum and plants. Review article.
AB  - The actin cytoskeleton plays a central part in the dynamic organization of
      eukaryotic cell structure. Nucleation of actin filaments is a crucial step in the
      establishment of new cytoskeletal structures or modification of existing ones,
      providing abundant targets for regulatory processes. A substantial part of our
      understanding of actin nucleation derives from studies on yeast and metazoan
      cells. However, recent advances in structural and functional genome analysis in
      less traditional models, such as plants or Dictyostelium discoideum, provide an
      emerging picture of an evolutionarily conserved core of at least two actin
      nucleation mechanisms, one mediated by the Arp2/3 complex and the other one by
      the formin-based module. A considerable degree of conservation is found also in
      the systems controlling the balance between filamentous and globular actin
      (profilin, actin-depolymerizing factor/cofilin) and even in certain regulatory
      aspects, such as the involvement of Rho-related small GTPases. Identification of
      such conserved elements provides a prerequisite for the characterization of
      evolutionarily variable aspects of actin regulation which may be responsible for
      the rich morphological diversity of eukaryotic cells.

PMID- 15726807
TI  - Morphohistological analysis and histochemistry of Feijoa sellowiana somatic
      embryogenesis.
AB  - Morphohistological analysis and histochemical studies were carried out during the
      induction and development of Feijoa sellowiana somatic embryos. Zygotic embryos
      were cultured on LPm medium containing 2,4-dichlorophenoxyacetic acid (20 microM)
      and glutamine (8 mM). Somatic embryogenesis could be induced from embryogenic
      cells that originated in meristematic centers or from clusters of cells. The
      presence of few starch grains and abundant protein bodies was observed in the
      globular and early torpedo stages, while in torpedo and cotyledonary-stage
      somatic embryos an enhanced synthesis of starch grains was associated with the
      accumulation of reserves to be used in the conversion of the embryos to
      plantlets. Proteins were predominantly observed in protoderm cells, as well as in
      the meristematic apical region of torpedo and cotyledonary-stage somatic embryos.

PMID- 15726808
TI  - Nuclear ploidy is contingent on the microtubular cycle responsible for plant
      cytokinesis.
AB  - Division of the plant cell relies on the preprophase band of microtubules (PPB)
      phragmoplast system. Cells of onion (Allium cepa L.) root meristems were rendered
      binucleate by preventing the consolidation of cell plate formation in telophase
      with 5 mM caffeine. These binucleates developed either a single PPB around one of
      their two nuclei or two PPBs, one per nucleus, in the prophase of the ensuing
      mitosis. Prophase cells developing one single PPB were shorter in length (42.3 +/
      4.1 microm) than those developing 2 PPBs (49.8 +/- 4.1 microm), and interphase
      duration was inversely related to cell length. Cells whose length was less than
      or equal to 42 microm, i.e., which had not even reached the mean size of the
      small binucleates in prophase, were followed throughout mitosis. In metaphase,
      they always assembled two mitotic spindles (one per nucleus). However, the cells
      that had assembled a single PPB also developed a single phragmoplast in
      telophase, leading to polyploidization. As these meristematic cells were not wide
      enough to accommodate the midzones of both mitotic spindles in any single plane
      transversal to the cell elongation axis, the spindles tilted until their midzones
      formed a continuum where the single common phragmoplast assembled. Its position
      was thereby uncoupled from that of the preceding PPB. Subsequently, the
      chromosomes from two different half-spindles were included, by a common nuclear
      envelope, in a single tetraploid nucleus. Finally, the cytokinetic plate
      segregated the two tetraploid nuclei formed at each side of the phragmoplast into
      two independent sister cells.

PMID- 15726809
TI  - Devescovinid features, a remarkable surface cytoskeleton, and epibiotic bacteria
      revisited in Mixotricha paradoxa, a parabasalid flagellate.
AB  - This work reports on the flagellate systematics and phylogeny, cytoskeleton,
      prokaryote-eukaryote cell junction organisation, and epibiotic bacteria
      identification. It confirms the pioneer 1964 study on Mixotricha paradoxa and
      supplies new information. Mixotricha paradoxa has a cresta structure specific to
      devescovinid parabasalid flagellates, a slightly modified recurrent flagellum,
      and an axostylar tube containing two lamina-shaped parabasal fibres. However,
      many parabasal profiles are distributed throughout the cell body. There is a
      conspicuous cortical microfibrillar network whose strands are related to cell
      junction structures subjacent to epibiotic bacteria. The supposed actin
      composition of this network could not be demonstrated with anti-actin antibodies
      or phalloidin labelling. Four types of epibiotic bacteria were described.
      Bacillus-shaped bacteria with a Gram-negative organisation are nested in
      alternate rows on most of the surface of the protozoon. They induce a striated
      calyxlike junction structure beneath the adhesion zone linked to the cortical
      microfibrillar network. Slender spirochetes are attached by one differentiated
      end to the plasma membrane of the protozoon, forming knobs on the cell surface.
      Two very similar long rod-shaped bacteria are also attached on the knobs of the
      plasma membrane. A large spirochete attributed to the genus Canaleparolina is
      also attached to the protozoon. Observations on epibiotic bacteria and of their
      attachments are compared with several described epibiotic bacteria of symbiotic
      protozoa and with the results of the molecular identification of the epibiotic
      bacteria of M. paradoxa.

PMID- 15726810
TI  - Comparison between the effects of fusicoccin, Tunicamycin, and Brefeldin A on
      programmed cell death of cultured sycamore (Acer pseudoplatanus L.) cells.
AB  - Programmed cell death occurs in plants during several developmental processes and
      during the expression of resistance to pathogen attack (i.e., the hypersensitive
      response). An unsolved question of plant programmed cell death is whether a
      unique signaling pathway or different, possibly convergent pathways exist. This
      problem was addressed in cultured sycamore (Acer pseudoplatanus L.) cells by
      comparing the effects of fusicoccin, Tunicamycin and Brefeldin A, inducers of
      programmed cell death with well-defined molecular and cellular targets, on some
      of the parameters involved in the regulation of this process. In addition to cell
      death, the inducers are able to stimulate the production of H2O2, the leakage of
      cytochrome c from mitochondria, the accumulation of cytosolic 14-3-3 proteins,
      and changes at the endoplasmic reticulum level, such as accumulation of the
      molecular chaperone binding protein and modifications in the organelle
      architecture. Interestingly, no additive effect on any of these parameters is
      observed when fusicoccin is administered in combination with Tunicamycin or
      Brefeldin A. Thus, these inducers seem to utilize the same or largely coincident
      pathways to induce programmed cell death and involvement of the endoplasmic
      reticulum, in addition to that of mitochondria, appears to be a common step.

PMID- 15726811
TI  - Nectar production and transportation in the nectaries of the female Cucumis
      sativus L. flower during anthesis.
AB  - In an effort to gain a greater understanding of nectar production, we studied the
      dynamic mechanisms of starch accumulation and transformation and nectar
      transportation in the Cucumis sativus L. female flower. Starch, which is the main
      precursor of nectar, accumulates in the epidermis and underlying parenchyma, with
      the most active accumulation occurring in the parenchyma cells within 3 days
      prior to anthesis. Thereafter, the starch was successively hydrolyzed and the
      hydrolyte was transported from the amyloplasts to vacuoles, suggesting that
      amyloplasts and vacuoles are the centers of nectar production. In addition, we
      observed few plasmodesmata and the presence of invaginated plasmalemma and
      electron-dense material in the intercellular spaces, suggesting that the apoplast
      system is involved in nectar transportation in an ATPase-dependent fashion.

PMID- 15726812
TI  - Regulation of nucleocytoplasmic localizatioin of the atDjC6 chaperone protein.
AB  - The sequence of the atDjC6 chaperone protein includes three potential nuclear
      localization signal (NLS) sequences (A-C) and three potential nuclear export
      signal (NES) sequences (X-Z). The subcellular localization of atDjC6 was studied
      by scanning laser confocal microscopy of chimera with the green-fluorescent
      protein (GFP) transiently expressed in tobacco BY-2 cells. The localization of
      the atDjC6::GFP chimera was coincident with that of the nuclear stain propidium
      iodide. Site-directed mutagenesis was used to verify the predicted NLS sequences.
      Each was individually fused to GFP and tested for protein localization. The
      individual NLS sequences were sufficient to direct partial nuclear localization
      of GFP, although the targeting information within NLS-B is apparently
      conformation sensitive. Site-directed mutagenesis of the NES sequences increased
      the amount of each chimera that was nuclearly localized, indicating a decrease in
      nuclear export. When any pair of NLS sequences were appended to GFP, the chimera
      were entirely nuclearly localized. Quantitative two-hybrid analysis was used to
      verify that the decoding of NLS sequence information involves interaction with
      the NLS-receptor protein importin-alpha. Each of the NLS sequences is flanked by
      a site of potential Ser phosphorylation, and recombinant atDjC6 could be
      phosphorylated in vitro. Mutagenesis of Ser residues to the P-Ser mimic Asp
      interfered with nuclear targeting, apparently by preventing recognition or
      binding by importin-alpha. Our results are consistent with a regulated
      nucleocytoplasmic localization of the atDjC6 chaperone protein.

PMID- 15726813
TI  - Root growth inhibition by aluminum is probably caused by cell death due to
      peroxidase-mediated hydrogen peroxide production.
AB  - The effect of aluminum on hydrogen peroxide production and peroxidase-catalyzed
      NADH oxidation was studied in barley roots germinated and grown between two
      layers of moistened filter paper. Guaiacol peroxidase activity significantly
      increased after 48 h and was approximately two times higher after 72 h in Al
      treated roots. The oxidation of NADH was also significantly increased and, like
      guaiacol peroxidase activity, it was two times higher in A1-treated roots than in
      controls. Elevated H2O2 production was observed both 48 and 72 h after the onset
      of imbibition in the presence of A1. Separation on a cation exchange column
      allowed the detection of two peaks with NADH peroxidase and H2O2 production
      activity. However, a difference between control and Al-treated plants was found
      only in one fraction, in which four times higher guaiacol peroxidase activity and
      five times higher NADH peroxidase activity were expressed and about three times
      more H2O2 was produced. One anionic peroxidase and three cationic peroxidases
      were detected in this fraction by native polyacrylamide gel electrophoresis. The
      anionic peroxidase was activated in the Al-treated root tips and also oxidized
      NADH but was detectable only after a long incubation time. Two of the cationic
      peroxidases were capable of oxidizing NADH and producing a significant amount of
      H2O2, but only one of these was activated by A1 stress. The role of these
      peroxidases during A1 stress in barley root tips is discussed.

PMID- 15726814
TI  - Effects of anoxia on root ultrastructure of four neotropical trees.
AB  - The root ultrastructure of seedlings grown in anaerobic conditions was
      investigated in four neotropical species: Sesbania virgata, Erythrina speciosa,
      Sebastiania commersoniana (all present in waterlogged or flooded areas), and
      Schizolobium parahyba (that occupies mainly dry areas). Anaerobiosis induced an
      increase in the size of mitochondria, dilatation of cristae and of the
      endoplasmic reticulum, and fragmentation or concentric arrangement of reticulum
      saccules. The ultrastructural alterations were reversible only for S. virgata and
      E. speciosa. The seedlings of S. parahyba and S. commersoniana were more
      sensitive to oxygen deprivation and presented extensive cell disruption. The
      results are discussed in terms of energy supply.

PMID- 15726815
TI  - Monokaryotic chloroplast mutation has no effect on non-Mendelian transmission of
      chloroplast and mitochondrial DNA in Chlamydomonas species.
AB  - We studied whether the monokaryotic chloroplast (moc) mutation affects the
      transmission of chloroplast and mitochondrial DNA in Chlamydomonas species. We
      used a previously isolated moc mutant from our cell line G33, which had only one
      large chloroplast nucleus. To obtain zygotes, we crossed the mutant cells with
      wild-type cells, and mutant cells with receptive mates (females [mt+] with males
      [mt-]). In these zygotes, we recorded preferential dissolution of mt- parental
      chloroplast nuclei and fusion of the two cell nuclei. Antibiotic-resistance
      markers of chloroplast DNA were maternally transmitted in all crosses. PCR
      analysis of the cytochrome b (cob) gene sequence showed that the mitochondrial
      DNA was paternally transmitted to offspring. These results suggest that the moc
      mutation did not affect the organelle DNA transmission.

PMID- 15726816
TI  - Rho/Rho-dependent kinase affects locomotion and actin-myosin II activity of
      Amoeba proteus.
AB  - The highly motile free-living unicellular organism Amoeba proteus has been widely
      used as a model to study cell motility. However, the molecular mechanisms
      underlying its unique locomotion are still scarcely known. Recently, we have
      shown that blocking the amoebae's endogenous Rac- and Rho-like proteins led to
      distinct and irreversible changes in the appearance of these large migrating
      cells as well as to a significant inhibition of their locomotion. In order to
      elucidate the mechanism of the Rho pathway, we tested the effects of blocking the
      endogenous Rho-dependent kinase (ROCK) by anti-ROCK antibodies and Y-27632, (+)
      (R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride, a
      specific inhibitor of ROCK, on migrating amoebae and the effect of the Rho and
      ROCK inhibition on the actin-activated Mg-ATPase of the cytosolic fraction of the
      amoebae. Amoebae microinjected with anti-ROCK inhibitors remained contracted and
      strongly attached to the glass surface and exhibited an atypical locomotion.
      Despite protruding many pseudopodia that were advancing in various directions,
      the amoebae could not effectively move. Immunofluorescence studies showed that
      ROCK-like protein was dispersed throughout the cytoplasm and was also found in
      the regions of actin-myosin II interaction during both isotonic and isometric
      contraction. The Mg-ATPase activity was about two- to threefold enhanced,
      indicating that blocking the Rho/Rho-dependent kinase activated myosin. It is
      possible then that in contrast to the vertebrate cells, the inactivation of
      Rho/Rho-dependent kinase in amoebae leads to the activation of myosin II and to
      the observed hypercontracted cells which cannot exert effective locomotion.

PMID- 15726817
TI  - Immunolocalisation of arabinogalactan proteins and pectins in Actinidia deliciosa
      pollen. Short communication.
AB  - The cell wall composition of germinating pollen grains of Actinidia deliciosa was
      studied by immunolocalization with monoclonal antibodies against arabinogalactan
      proteins (AGPs) and pectins. In ungerminated pollen, the JIM8 epitope (against a
      subset of AGPs) was located in the intine and in the cytoplasm, while the MAC207
      epitope (against AGPs) was located only in the exine. After germination, the JIM8
      and MAC 207 epitopes were located in the cytoplasm and in the pollen tube wall.
      The Yariv reagent that binds to AGPs was added to the germination medium inducing
      a reduction or inhibition in pollen germination. This indicates that AGPs are
      present in the growing pollen tube and play an important role in pollen
      germination. To identify the nature of the pectins found in pollen grains and
      tubes, four monoclonal antibodies were used. The JIM5 epitope (against
      unesterifled pectins) was located in the intine, more intensely in the pore
      region, and along the pollen tube wall, and the JIM7 epitope (against
      methylesterified pectins) was also observed in the cytoplasm. After germination,
      the JIM5 epitope was located in the pollen tube wall; although, the tube tip was
      not labelled. The JIM7 epitope was located in the entire pollen tube wall. LM5
      (against galactans) showed a labelling pattern similar to that of JIM5 and the
      pattern of LM6 (against arabinans) was similar to that of JIM7. Pectins show
      different distribution patterns when the degree of esterification is considered.
      Pollen tube wall pectins are less esterified than those of the pollen tube tip.
      The association of AGPs with pectins in the cell wall of the pollen grain and the
      pollen tube may play an important role in the maintenance of cell shape during
      pollen growth and development.

PMID- 15726818
TI  - Structure and function of animal fatty acid synthase.
AB  - Fatty acid synthase (FAS; EC 2.3.1.85) of animal tissues is a complex
      multifunctional enzyme consisting of two identical monomers. The FAS monomer
      (approximately 270 kDa) contains six catalytic activities and from the N-terminus
      the order is beta-ketoacyl synthase (KS), acetyl/malonyl transacylase (AT/MT),
      beta-hydroxyacyl dehydratase (DH), enoyl reductase (ER), beta-ketoacyl reductase
      (KR), acyl carrier protein (ACP), and thioesterase (TE). Although the FAS monomer
      contains all the activities needed for palmitate synthesis, only the dimer form
      of the synthase is functional. Both the biochemical analyses and the small-angle
      neutron-scattering analysis determined that in the dimer form of the enzyme the
      monomers are arranged in a head-to-tail manner generating two centers for
      palmitate synthesis. Further, these analyses also suggested that the component
      activities of the monomer are organized in three domains. Domain I contains KS,
      AT/MT, and DH, domain II contains ER, KR, and ACP, and domain III contains TE.
      Approximately one fourth of the monomer protein located between domains I and II
      contains no catalytic activities and is called the interdomain/core region. This
      region plays an important role in the dimer formation. Electron cryomicrographic
      analyses of FAS revealed a quaternary structure at approximately 19 A resolution,
      containing two monomers (180 x 130 x 75 A) that are separated by about 19 A, and
      arranged in an antiparallel fashion, which is consistent with biochemical and
      neutron-scattering data. The monomers are connected at the middle by a hinge
      generating two clefts that may be the two active centers of fatty acid synthesis.
      Normal mode analysis predicted that the intersubunit hinge region and the
      intrasubunit hinge located between domains II and III are highly flexible.
      Analysis of FAS particle images by using a simultaneous multiple model single
      particle refinement method confirmed that FAS structure exists in various
      conformational states. Attempts to get higher resolution of the structure are
      under way.

PMID- 15726819
TI  - The reductase steps of the type II fatty acid synthase as antimicrobial targets.
AB  - The increasing of multidrug resistance of clinically important pathogens calls
      for the development of novel antibiotics with unexploited cellular targets. FA
      biosynthesis in bacteria is catalyzed by a group of highly conserved proteins
      known as the type II FA synthase (FAS II) system. Bacterial FAS II organization
      is distinct from its mammalian counterpart; thus the FAS II pathway offers
      several unique steps for selective inhibition by antibacterial agents. Some known
      antibiotics that target the FAS II system include triclosan, isoniazid, and
      thiolactomycin. Recent years have seen remarkable progress in the understanding
      of the genetics, biochemistry, and regulation of the FAS II system with the
      availability of the complete genome sequence for many bacteria. Crystal
      structures of the FAS II pathway enzymes have been determined for not only the
      Escherichia coli model system but also other gram-negative and gram-positive
      pathogens. The protein structures have greatly facilitated structure-based design
      of novel inhibitors and the improvement of existing antibacterial agents. This
      review discusses new developments in the discovery of inhibitors that
      specifically target the two reductase steps of the FAS II system, beta-ketoacyl
      acyl carrier potein (ACP) reductase and enoyl-ACP reductase.

PMID- 15726821
TI  - Progress toward the production of long-chain polyunsaturated fatty acids in
      transgenic plants.
AB  - Long-chain PUFA such as eicosapentaenoic and docosahexaenoic acids are prevalent
      in fish oils, and these compounds have been demonstrated to play important roles
      in human health and nutrition. In particular, these n-3/omega-3 long-chain PUFA
      provide protection from cardiovascular disease and a collection of symptoms
      (termed metabolic syndrome) associated with progression toward type 2 diabetes
      and obesity. Within Western populations, a large increase in the occurrence of
      these conditions represents a major public health concern. Unfortunately, both
      marine fish stocks and (consequentially) consumption of fish oils are in steep
      decline, limiting the protective role of long-chain PUFA in human health. One
      alternative approach to the provision of these health-beneficial FA is via their
      synthesis in transgenic plants. This review will describe recent advances in the
      production of transgenic plant oils nutritionally enhanced to produce long-chain
      PUFA.

PMID- 15726820
TI  - Regulation of stearoyl-CoA desaturase expression.
AB  - Stearoyl-CoA desaturase (SCD) is a regulatory enzyme in lipogenesis, catalyzing
      the rate-limiting step in the overall de novo synthesis of monounsaturated FA,
      mainly oleate and palmitoleate from stearoyl- and palmitoyl-CoA, respectively.
      Oleate and palmitoleate are the major monounsaturated FA of membrane
      phospholipids, TG, wax esters, cholesterol esters, and alkyldiacylglycerol.
      Several SCD gene isoforms (SCD1, SCD2, SCD3, and SCD4) exist in mice, and two
      have been characterized in humans. SCD1 gene expression in liver cells is
      regulated by numerous stimuli including diet and hormones. We are interested in
      why SCD is such a highly regulated enzyme even though oleate, the major product
      of this enzyme, is one of the most abundant FA in the diet and is therefore
      readily available. Dietary oleate is also well known for its TG-lowering effects
      and, as a major component of olive oil, is expected to have beneficial effects.
      However, high SCD activity has been implicated in diabetes, obesity,
      atherosclerosis, and cancer in several animal models; therefore, the role that de
      novo oleate plays in these disease states has to be carefully evaluated. By using
      SCD1-/- mice, which are deficient in tissue oleate, we begin to learn more about
      the physiological role of SCD gene expression and oleate in normal and disease
      states.

PMID- 15726823
TI  - Molecular characterization of three peroxisome proliferator-activated receptors
      from the sea bass (Dicentrarchus labrax).
AB  - Peroxisome proliferator-activated receptors (PPAR) are nuclear hormone receptors
      that control the expression of genes involved in lipid homeostasis in mammals. We
      searched for PPAR in sea bass, a marine fish of particular interest to
      aquaculture, after hypothesizing that the physiological and molecular processes
      that regulate lipid metabolism in fish are similar to those in mammals. Here, we
      report the identification of complementary DNA and corresponding genomic
      sequences that encode three distinct PPAR from sea bass. The sea bass PPAR are
      the structural homologs of the mammalian PPAR alpha, beta/delta, and gamma
      isotypes. As revealed by RNase protection, the tissue expression profile of the
      fish PPAR appears to be very similar to that of the mammalian PPAR homologs.
      Thus, PPAR alpha is mainly expressed in the liver, PPAR gamma in adipose tissue,
      and PPAR beta in all tissues tested, with its highest levels in the liver, where
      it is also the dominant isotype expressed. Like mammalian PPAR, the sea bass
      isotypes recognize and bind to PPAR response elements of both mammalian and
      piscine origin, as heterodimers with the 9-cis retinoic acid receptor. Through
      the coactivator-dependent receptor ligand assay, we also demonstrated that
      natural FA and synthetic hypolipidemic compounds can act as ligands of the sea
      bass PPAR alpha and beta isotypes. This suggests that the sea bass PPAR act
      through similar mechanisms and perform the same critical lipid metabolism
      functions as mammalian PPAR.

PMID- 15726822
TI  - Mechanisms of regulation of gene expression by fatty acids.
AB  - Fatty acids (FA) regulate the expression of genes involved in lipid and energy
      metabolism. In particular, two transcription factors, sterol regulatory element
      binding protein-1c (SREBP-1c) and peroxisome proliferator activated receptor
      alpha (PPARalpha), have emerged as key mediators of gene regulation by FA. SREBP
      1c induces a set of lipogenic enzymes in liver. Polyunsaturated fatty acids
      (PUFA), but not saturated or monounsaturated FA, suppress the induction of
      lipogenic genes by inhibiting the expression and processing of SREBP-1c. This
      unique effect of PUFA suggests that SREBP-1c may regulate the synthesis of
      unsaturated FA for incorporation into glycerolipids and cholesteryl esters.
      PPARalpha plays an essential role in metabolic adaptation to fasting by inducing
      the genes for mitochondrial and peroxisomal FA oxidation as well as those for
      ketogenesis in mitochondria. FA released from adipose tissue during fasting are
      considered as ligands of PPARalpha. Dietary PUFA, except for 18:2 n-6, are likely
      to induce FA oxidation enzymes via PPARalpha as a "feed-forward " mechanism.
      PPARalpha is also required for regulating the synthesis of highly unsaturated FA,
      indicating pleiotropic functions of PPARalpha in the regulation of lipid
      metabolic pathways. It is yet to be determined whether FA regulate other
      transcription factors such as liver-X receptor, hepatocyte nuclear factor 4, and
      carbohydrate response element binding protein.

PMID- 15726824
TI  - Functions of peroxisome proliferator-activated receptors (PPAR) in skin
      homeostasis.
AB  - The peroxisome proliferator-activated receptors (PPAR) are ligand-activated
      transcription factors that belong to the nuclear hormone receptor family. Three
      isotypes (PPAR alpha, PPAR beta or delta, and PPAR gamma) with distinct tissue
      distributions and cellular functions have been found in vertebrates. All three
      PPAR isotypes are expressed in rodent and human skin. They were initially
      investigated for a possible function in the establishment of the permeability
      barrier in skin because of their known function in lipid metabolism in other cell
      types. In vitro studies using specific PPAR agonists and in vivo gene disruption
      approaches in mice indeed suggest an important contribution of PPAR alpha in the
      formation of the epidermal barrier and in sebocyte differentiation. The PPAR
      gamma isotype plays a role in stimulating sebocyte development and lipogenesis,
      but does not appear to contribute to epidermal tissue differentiation. The third
      isotype, PPAR beta, regulates the late stages of sebaceous cell differentiation,
      and is the most effective isotype in stimulating lipid production in these cells,
      both in rodents and in humans. In addition, PPAR beta activation has pro
      differentiating effects in keratinocytes under normal and inflammatory
      conditions. Finally, preliminary studies also point to a potential role of PPAR
      in hair follicle growth and in melanocyte differentiation. By their diverse
      biological effects on cell proliferation and differentiation in the skin, PPAR
      agonists or antagonists may offer interesting opportunities for the treatment of
      various skin disorders characterized by inflammation, cell hyperproliferation,
      and aberrant differentiation.

PMID- 15726825
TI  - What's so special about cholesterol?
AB  - Cholesterol (or other higher sterols such as ergosterol and phytosterols) is
      universally present in large amounts (20-40 mol%) in eukaryotic plasma membranes,
      whereas it is universally absent in the membranes of prokaryotes. Cholesterol has
      a unique ability to increase lipid order in fluid membranes while maintaining
      fluidity and diffusion rates. Cholesterol imparts low permeability barriers to
      lipid membranes and provides for large mechanical coherence. A short topical
      review is given of these special properties of cholesterol in relation to the
      structure of membranes, with results drawn from a variety of theoretical and
      experimental studies. Particular focus is put on cholesterol's ability to promote
      a special membrane phase, the liquid-ordered phase, which is unique for
      cholesterol (and other higher sterols like ergosterol) and absent in membranes
      containing the cholesterol precursor lanosterol. Cholesterol's role in the
      formation of special membrane domains and so-called rafts is discussed.

PMID- 15726826
TI  - Transient confinement zones: a type of lipid raft?
AB  - Many important signaling events are initiated at the cell membrane. To facilitate
      efficient signal transduction upon stimulation, membrane microdomains, also known
      as lipid rafts, are postulated to serve as platforms to recruit components
      involved in the signaling complex, but few methods exist to study rafts in vivo.
      Single particle tracking provides an approach to study the plasma membrane of
      living cells on the nano-scale. The trajectories of single gold particles bound
      to membrane proteins and lipids are characterized in terms of both random and
      confined diffusion; the latter occurs in "transient confinement zones". Here we
      review transient confinement zones and some of their implications for membrane
      structure and function.

PMID- 15726827
TI  - Environmental light and heredity are associated with adaptive changes in retinal
      DHA levels that affect retinal function.
AB  - Retinas of rats and mice react to environmental and genetic stimuli by altering
      the level of DHA in their rod outer segment membranes. We propose that this
      adaptation is a neuroprotective response to control the number of photons
      captured by rhodopsin and the efficiency of visual transduction, under conditions
      where excessive activation of the transduction cascade could lead to cell death.

PMID- 15726828
TI  - Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators,
      and their endogenous aspirin-triggered epimers.
AB  - The molecular basis for the beneficial impact of essential omega-3 (n-3) FA
      remains of interest. Recently, we identified novel mediators generated from
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that displayed potent
      bioactions identified first in resolving inflammatory exudates and in tissues
      enriched with DHA. The trivial names resolvin (resolution phase interaction
      products) and docosatrienes were introduced for the bioactive compounds from
      these novel series since they possess potent anti-inflammatory and
      immunoregulatory actions. Compounds derived from EPA carrying potent biological
      actions (i.e., 1-10 nM range) are designated E series and denoted resolvins of
      the E series (resolvin E1 or RvE1), and those biosynthesized from the precursor
      DHA are denoted resolvins of the D series (resolvin D1 or RvD1). The number 1
      designates the bioactive compounds in this family (#1-4). Bioactive members from
      DHA-containing conjugated triene structures or docosatrienes (DT) that possess
      immunoregulatory and neuroprotective actions were termed neuroprotectins. Aspirin
      treatment initiates a related epimeric series by triggering endogenous formation
      of the 17R-D series resolvins and docosatrienes. These epimers are denoted as
      aspirin-triggered (AT)-RvD and DT, and possess potent anti-inflammatory actions
      in vivo essentially equivalent to their 17S series pathway products. These
      include five distinct series: (i) 18R resolvins from EPA (i.e., RvE1); (ii) 17R
      series (AT) resolvins from DHA (RvD1 through RvD4); (iii) 17S series resolvins
      from DHA (RvD1 through RvD4), (iv) DT from DHA; and (v) their AT form 17R series
      DT. In this article, we provide an overview of the formation and actions of these
      newly uncovered pathways and products.

PMID- 15726830
TI  - Conjugated linoleic acids (CLA) as precursors of a distinct family of PUFA.
AB  - One of the possibilities for distinct actions of c9,t11- and the t10,c12
      conjugated linoleic acid (CLA) isomers may be at the level of metabolism since
      the conjugated diene structure gives to CLA isomers and their metabolites a
      distinct pattern of incorporation into the lipid fraction and metabolism. In
      fact, CLA appears to undergo similar transformations as linoleic acid but with
      subtle isomer differences, which may account for their activity in lowering
      linoleic acid metabolites in those tissues rich in neutral lipids where CLA is
      preferentially incorporated. Furthermore, c9,t11 and t10,c12 isomers are
      metabolized at a different rate in the peroxisomes, where the shortened
      metabolite from t10,c12 is formed at a much higher proportion than the metabolite
      from c9,t11. This may account for the lower accumulation of t10,c12 isomer into
      cell lipids. CLA isomers may therefore be viewed as a "new" family of
      polyunsaturated fatty acids (PUFA) producing a distinct range of metabolites
      using the same enzymatic system as the other (i.e., n-3, n-6 and n-9) PUFA
      families. It is likely that perturbation of PUFA metabolism by CLA will have an
      impact on eicosanoid formation and metabolism, closely linked to the biological
      activities attributed to CLA.

PMID- 15726831
TI  - Microvessels promote motor nerve survival and regeneration through local VEGF
      release following ectopic reattachment.
AB  - OBJECTIVES: Nerves and blood vessels form a close association during
      embryogenesis. Growth and guidance factors initially attributed to either nerves
      or vessels are now known to affect both tissues; prominent among these is
      vascular endothelial growth factor (VEGF). The authors investigated whether axons
      would associate with blood vessels in a regenerating system and questioned
      whether VEGF is integral to neurotization following axotomy. METHODS: In hamsters
      8-12 weeks of age, the accessory nerve (CN XI) to the retractor muscle of the
      cheek pouch was cut and the proximal stump was reattached ectopically onto the
      muscle. Vascular casting and immunolabeling were used to quantify the extent of
      neurovascular association during regeneration. A role for VEGF was investigated
      using immunolocalization of VEGF and its receptor (sVEGFR2) as well as local
      sequestration of VEGF with soluble receptor (sVEGFR1). RESULTS: Regenerating
      axons aligned with microvessels of the vasa nervorum along a "chaperone" region
      during outgrowth from the reattachment site and while entering the muscle. In
      this approximately 1-mm region, VEGF protein was expressed by growing
      microvessels despite a approximately 50% reduction (p < .05) in total muscle VEGF
      concentration. VEGFR2 was expressed by regenerating axons and growth cones.
      Sequestration of VEGF by sVEGFR1 impaired neurotization by approximately 40% (p <
      .05). The chaperone region ended where regenerating microvessels anastomosed with
      the native microcirculation and their expression of VEGF protein diminished.
      CONCLUSIONS: Regenerating axons and blood vessels align during outgrowth from
      ectopic reattachment. This interaction dissipates as vascular anastomoses form
      with established microvessels and axons target muscle fibers. Local production of
      VEGF by growing microvessels supports motor nerve survival and regeneration.

PMID- 15726829
TI  - Cytochrome c release is required for phosphatidylserine peroxidation during Fas
      triggered apoptosis in lung epithelial A549 cells.
AB  - Oxidation of phosphatidylserine (PtdSer) has been shown to play a pivotal role in
      signaling during cell apoptosis and subsequent recognition of apoptotic cells by
      phagocytes. However, the redox catalytic mechanisms involved in selective PtdSer
      oxidation during apoptosis remain poorly understood. Here we employed anti-Fas
      antibody CH-11-treated A549 cells as a physiologically relevant model to
      investigate the involvement of PtdSer oxidation and its potential mechanism
      during apoptosis. We demonstrated that ligation of CH-11 with its cognate
      receptor initiated execution of apoptotic program in interferon gamma-pretreated
      A549 cells as evidenced by activation of caspase and DNA fragmentation. A
      significant increase of cytochrome c (cyt c) content in the cytosol as early as 2
      h after CH-11 exposure was detected indicating that Fas-induced apoptosis in A549
      cells proceeds via extrinsic type II pathway and includes mitochondrial
      signaling. PtdSer was selectively oxidized 3 h after anti-Fas triggering while
      two more abundant phospholipids--phosphatidylcholine (PtdCho) and
      phosphatidylethanolamine (PtdEtn)--and the major intracellular antioxidant,
      glutathione, remained nonoxidized. A pan-caspase inhibitor, z-VAD, fully blocked
      cyt c release and oxidation of PtdSer in Fas-treated A549 cells. On the other
      hand, z-DQMD, a caspase-3 inhibitor, completely inhibited caspase-3 activity but
      did not fully block caspase-8 activation and release of cyt c. Importantly, z
      DQMD failed to protect PtdSer from oxidation. In addition, in a model system, we
      demonstrated that peroxidase activity of cyt c was greatly enhanced in the
      presence of dioleoylphosphatidylserine containing liposomes by monitoring
      oxidation of 2',7'-dichlorodihydrofluorescein to 2',7'-dichlorofluorescein. We
      further showed that peroxidase activity of cyt c catalyzed oxidation of 1
      palmitoyl-2-arachidonoyl-3-glycero-phosphoserine using a newly developed HPLC
      assay. MS analysis of 1-palmitoyl-2-arachidonoyl-3-glycero-phosphoserine revealed
      that in addition to its mono- and dihydroperoxides, several different PtdSer
      oxidation products can be formed. Overall, we concluded that cyt c acts as a
      catalyst of PtdSer oxidation during Fas-triggered A549 cell apoptosis.

PMID- 15726832
TI  - Inhibition of leukocyte adherence enables venular control of capillary perfusion
      in streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: Vasoactive molecules can diffuse from venules to dilate closely paired
      arterioles and enhance capillary perfusion. Venular control of capillary flow has
      been found to be dependent on nitric oxide (NO), which might be scavenged rapidly
      in diabetic microvasculature due to the presence of activated leukocytes. This
      study attempts to improve venular control of capillary flow using fucoidan, which
      inhibits venular leukocvte adhesion. METHODS: Microvascular red blood cell
      velocity was measured in the mesentery of streptozotocin-induced diabetic rats,
      with and without fucoidan treatment, and in normal rats. Arteriolar pathways
      leading to branching capillaries were videotaped to measure the percent of the
      surrounding area occupied by a venule (% pairing). Microvascular wall NO was
      measured using fluorescent diaminofluorescein-2-diacetate in diabetic rats, with
      and without fucoidan treatment. RESULTS: In normal rats, close pairing of venules
      to arterioles resulted in faster capillary flow. However, after 4-5 weeks of
      diabetes, the correlation between capillary velocity and % pairing was no longer
      significant. Capillary velocity and % pairing decreased approximately 50% in
      comparison to normal rats. Treatment of diabetic rats with fucoidan restored
      venular control of capillary flow and increased NO levels. CONCLUSION: Leukocyte
      derived mediators that scavenge NO may lead to inadequate venular control of
      capillary flow in diabetes.

PMID- 15726833
TI  - Relative contributions of alpha4 and alphaL integrins to IL-4-induced leukocyte
      rolling and adhesion.
AB  - OBJECTIVE: To delineate the relative contributions of alpha4 and alphaL to
      mediate interleukin-4 (IL-4) induced leukocyte rolling, and the subsets of
      leukocytes that use these pathways to adhere. METHODS: Intravital microscopy was
      used to examine leukocytes in venules of cremaster muscles of mice receiving
      intrascrotal injections of IL-4. alpha4 and alphaL monoclonal antibodies (mAbs)
      were administrated either prior to (prophylactic) or 24 h following (therapeutic)
      treatment with IL-4. In addition, fluorescent microspheres coated with mAbs
      directed against CD4, CD8, or Gr-1 were injected into mice and the number of
      subset-specific adherent leukocytes was measured. RESULTS: Prophylactic
      inhibition of alpha4 and alphaL integrins prevented IL-4-induced leukocyte
      rolling flux (p< .05) and increased leukocyte rolling velocity twofold (p < .05),
      respectively, while blocking either integrin eliminated IL-4-induced leukocyte
      adhesion (p < .05). In contrast, therapeutic administration of both anti-alpha4
      and anti-alphaL mAbs was necessary to completely inhibit IL-4-induced leukocyte
      adhesion (p < .05). Furthermore, CD8+ and Gr-1+ leukocytes utilized alpha4 and
      alphaL to adhere to postcapillary venules, whereas CD4+ leukocytes primarily
      utilized alpha4. CONCLUSIONS: Following tissue activation with IL-4, alpha4 and
      alphaL initiate the attachment and deceleration, respectively, of leukocytes
      during rolling, and are responsible for mediating the adhesion CD4+, CD8+, Gr-1+
      leukocytes.

PMID- 15726834
TI  - Arteriolar responses to vasodilator stimuli and elevated P(O2) in renin congenic
      and Dahl salt-sensitive rats.
AB  - OBJECTIVES: Angiotensin II suppression leads to impaired vascular relaxation in
      normotensive animals on a high-salt diet. The goal of this study was to determine
      whether normal vascular reactivity could be restored by transferring the
      chromosomal region carrying the Dahl salt-resistant (R) renin gene into the Dahl
      salt-sensitive (SS) genetic background in a strain of renin congenic rats (RGRR).
      METHODS: Male RGRR and SS rats were fed low-salt (0.4%) and high-salt (4%) diets
      for 4 weeks. The responses of cremaster muscle arterioles to acetylcholine (ACh),
      sodium nitroprusside (SNP), and elevated PO2 were assessed using video
      microscopy. RESULTS: ACh-induced dilation was significantly enhanced in RGRR on a
      high-salt diet compared to SS rats, while dilation to the NO donor SNP was
      similar in both strains. A high-salt diet significantly enhanced arteriolar
      constriction in response to elevated PO2, in both SS and RGRR rats. CONCLUSIONS:
      These data suggest that transfer of the chromosomal region containing the renin
      gene is crucial in the recovery of ACh-induced dilation of arterioles in RGRR
      rats vs. SS rats, and that factors in the SS genetic background contribute to an
      enhanced sensitivity to elevated PO2, independent of genes on chromosome 13.

PMID- 15726836
TI  - Increased expression of vascular endothelial growth factor and capillary density
      in hearts of spontaneously hypertensive rats.
AB  - OBJECTIVE: The role of VEGF in vascular remodeling of target organs exposed to
      chronic hypertension is poorly understood. The authors compared capillary density
      (CD), capillary-to-fiber ratio (C/F), and VEGF mRNA expression in the hearts
      (left ventricle [LV]), and skeletal muscles (soleus and anterior tibialis [AT])
      of 18-week-old male spontaneously hypertensive rats (SHR) and age-matched male
      Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. METHODS: CD or C/F in LV,
      soleus, and AT of SHR, WKY, and SD rats was determined by analysis of randomly
      acquired digital images of cryosections stained with FITC-conjugated GS-I lectin.
      VEGF mRNA expressions in the tissues were determined by Northern blot. RESULTS:
      VEGF mRNA expressions in LV of SHR were 3.84- and 5.05-fold higher, compared to
      SD and WKY rats, respectively (n = 6; p < .01). There were no significant
      differences in VEGF mRNA expression in soleus or AT among SHR, WKY, and SD rats
      (p > .05). CD in LV of SHR (4975 +/- 167) was significantly higher than WKY or SD
      rats, 4151 +/- 169 and 3807 +/- 187 mm(-2), respectively (p < .05). In LV of SHR,
      C/F increased (35%) more significantly than CD (increased 20%), compared to WKY
      rats. CD, or C/F in soleus or AT of SHR was similar to that observed in WKY or 8D
      rats. CONCLUSIONS: VEGF expression, CD, and C/F in the heart (LV) of SHR are
      significantly increased, compared to WKY and SD rats. The data are consistent
      with the possibility that VEGF may contribute to capillary growth as a
      compensatory response to hypertension.

PMID- 15726835
TI  - Pentastarch in a balanced solution reduces hepatic leukocyte recruitment in early
      sepsis.
AB  - OBJECTIVE: To characterize the hepatic leukocyte endothelial cell interactions
      occurring in early sepsis and to determine whether this is influenced by fluid
      treatment. METHODS: Sepsis was induced by cecal ligation and perforation in
      C57Bl/6 mice. One of 6 iv fluid regimes was given immediately postsurgery and at
      6 h. The hepatic microcirculation was examined by intravital microscopy at 6 h.
      RESULTS: All 0.9% saline-based solutions were associated with an increase in
      leukocyte-endothelial cell interactions as demonstrated by an increase in the
      rolling flux in the sham and naive mice. In the septic mice treated with normal
      saline, there was a 20-fold increase in leukocyte adhesion within the
      postsinusoidal venules, compared to sham mice. Treatment with lactated Ringer's
      reduced the sepsis-mediated leukocyte recruitment by 50%. When septic mice
      received 6% pentastarch in a balanced solution or 3% saline, venular leukocyte
      adhesion was reduced by an additional 50%. When the pentastarch was prepared in
      normal saline there was no further reduction in venular leukocyte adhesion
      compared to the lactated Ringer's-treated mice. All hyperosmolar solutions
      improved the sepsis-induced reduction in sinusoidal perfusion but only the
      pentastarch in the balance solution significantly reduced the number of adherent
      leukocytes within the sinusoids. CONCLUSIONS: Hepatic leukocyte recruitment
      occurs early in sepsis. Pentastarch in a balanced solution but not in normal
      saline significantly reduces hepatic leukocyte recruitment, suggesting solution
      composition, as well as osmolarity impact the innate immune response.

PMID- 15726837
TI  - Incorporation of naive bone marrow derived cells into the vascular architecture
      of brain tumor.
AB  - OBJECTIVE: Neovascularization is essential for tumor growth and invasion.
      Mounting evidence suggests that tumor cells recruit circulating endothelial
      progenitor cells to promote vasculogenesis to compliment tumor angiogenesis. This
      study examines the constitutive role of bone marrow-derived cells in this
      process. METHODS: Rat glioma cells were implanted into brains of T-cell-depleted
      knockout mice. At various timepoints after tumor implantation, naive bone marrow
      cells from ubiquitous transgenic mice expressing green fluorescent protein (GFP)
      were infused into these animals. The incorporation of GFP-positive cells into the
      vascular architecture was visualized by fluorescence confocal microscopy in
      conjunction with the transcription profiles of vascular endothelial growth factor
      (VEGF) and angiopoietin-1 and -2 (Ang-1 and Ang-2). RESULTS: Of the cells
      infused, 8 days after tumor implantation, 0.49% were found exclusively
      sequestered in the vicinity of tumor vessels. This coincided with a decline in
      the expression of Ang-1 and a rise in the expression of VEGF and Ang-2. A few of
      these cells (0.66 of the 0.49%) localized onto the vascular wall. They resembled
      endothelial cells and expressed vWF. CONCLUSION: The incorporation of bone marrow
      derived unpurified endothelial cells into the tumor vascular bed is both time
      limited and infrequent. These cells may play a supportive rather than a
      constitutive role in tumor neovascularization.

PMID- 15726839
TI  - Auditory measures in clinically depressed individuals. I. Basic measures and
      transient otoacoustic emissions.
AB  - This is the first paper in a series of two papers addressing possible differences
      in auditory function between individuals with and without clinical depression.
      Clinical depression is a common yet serious medical condition diagnosed based on
      the patient's symptoms. Selective serotonin reuptake inhibitors (SSRIs) are
      widely prescribed if the symptoms are determined to be consistent with low
      serotonin levels. Three groups of individuals were tested: the control group
      consisted of subjects with no depression; the medicated group consisted of
      subjects with depression who were on SSRIs for at least a month: the unmedicated
      group consisted of subjects with depression who were unmedicated for at least a
      month. The results indicated no significant differences between the groups in
      pure-tone threshold, uncomfortable loudness levels, dynamic range of hearing, and
      acoustic reflex thresholds However, the unmedicated group exhibited higher
      amplitudes of transient otoacoustic emissions compared to the control group,
      especially in the right ear.

PMID- 15726838
TI  - Antecedent ethanol ingestion prevents postischemic P-selectin expression in
      murine small intestine.
AB  - OBJECTIVE: Ethanol ingestion 24 h prior to ischemia and reperfusion (I/R)
      prevents postischemic leukocyte rolling and adhesion in postcapillary venules of
      the small bowel. Since I/R-induced leukocyte rolling is critically dependent on
      the expression of P-selectin by endothelial cells lining postcapillary venules,
      the authors hypothesized that antecedent ethanol consumption would attenuate
      postischemic expression of this adhesive ligand. METHODS: To address this
      postulate, P-selectin expression was evaluated using a dual radiolabeled
      monoclonal antibody technique in the jejunum of mice that received either
      distilled water vehicle or ethanol by gavage (dose) on day 1 and then were
      subjected to sham I/R (nonischemic controls) or I/R (20 min ischemia/60 min
      reperfusion) 24 h later. RESULTS: I/R was associated with a 2-fold increase in P
      selectin expression relative to nonischemic controls, an effect that was largely
      abolished by antecedent ethanol ingestion. Exposing the bowel to adenosine
      deaminase or adenosine A2 receptor antagonists (DMPX or ZM241385), an NO synthase
      inhibitor (L-NIO) or an NO scavenger (PTIO), or an antioxidant
      (mercaptoproprionyl glycine) during the period of ethanol exposure on day 1
      prevented the beneficial effect of ethanol to limit I/R-induced P-selectin
      expression, on day 2. CONCLUSIONS: The data indicate that antecedent ethanol
      exposure prevents postischemic P-selectin expression on day 2 by a mechanism that
      is triggered by adenosine A2 receptor activation and the formation of nitric
      oxide (NO) and reactive oxygen species (ROS) during the period of ethanol
      exposure on day 1.

PMID- 15726841
TI  - Is age at implant the only factor that counts? The influence of working memory on
      lexical and grammatical development in children with cochlear implants.
AB  - In this study, we explored the influence of time factors (age at implant, time
      with cochlear implant and age), complex working memory and phonological short
      term memory on lexical and grammatical development in congenitally deaf children
      with cochlear implants. Fifteen children (aged 5 years 4 months to 11 years 5
      months) were examined with the use of several linguistic and cognitive measures
      after a minimum of 18 months of implant use. Phonological short-term memory was
      assessed with non-word repetition, where the percentage of correctly repeated
      consonants and vowels was counted. For the assessment of lexical acquisition. a
      novel word learning task was administered. Receptive and expressive grammar was
      tested. Our results corroborate earlier findings on the influence of phonological
      short-term memory on novel word learning. The percentage of vowels correctly
      produced in non-word repetition was more important in this group than age at
      implant, not only for novel word learning. but also for receptive and expressive
      grammar.

PMID- 15726842
TI  - Auditory neuropathy in hyperbilirubinemia: is there a correlation between serum
      bilirubin, neuron-specific enolase levels and auditory neuropathy?
AB  - This study evaluated whether a correlation exists between increased serum
      bilirubin and neuron-specific enolase (NSE) assays (a biochemical index of
      neuronal damage) and auditory neuropathy. Nineteen term neonates without
      hemolysis whose serum bilirubin levels were above 20 mg/dl and 27 healthy term
      newborns with bilirubin levels <13 mg/dl were included in the study. Auditory
      brainstem responses (ABRs) and transient evoked otoacoustic emissions (TEOAEs) of
      patients with hyperbilirubinemia were obtained before discharge. This preliminary
      study did not show any correlation between the serum NSE and bilirubin values.
      However, infants who had auditory neuropathy had significantly higher NSE levels,
      and thus these patients, being in the high-risk group, need close follow-up.

PMID- 15726840
TI  - Auditory measures in clinically depressed individuals. II. Auditory evoked
      potentials and behavioral speech tests.
AB  - This is the second paper in a series of two papers comparing auditory measures in
      depressed and non-depressed individuals. In this paper, we describe the auditory
      brainstem responses (ABRs), auditory late responses (ALRs) and behavioral speech
      measures obtained from the same set of 36 individuals as in our previous paper.
      No changes were made to the inclusion criteria or subject classification. The
      results indicated a significantly larger amplitude growth with increase in
      intensity for ABR peak V and ALR peak N1P2 in the unmedicated group compared to
      the normal group. The unmedicated group performed less favorably on most
      behavioral speech tests administered compared to the control group, but the
      difference was significant only in the left ear for the Low Predictability
      Sentence List of the R-SPIN (Revised-Speech Perception in Noise) test. The mean
      test scores of the medicated group were closer to the scores of the control
      group.

PMID- 15726843
TI  - Evidence of progression and fluctuation of hearing impairment in branchio-oto
      renal syndrome.
AB  - We retrospectively analysed long-term serial audiometry data from patients with
      branchio-oto-renal (BOR) syndrome to show the features of progression and
      fluctuation in hearing impairment and relate the findings to age and magnetic
      resonance imaging (MRI) findings in the petrosal bones. Thirty-two clinically
      affected BOR patients from six Dutch families (A-F) were included. Audiograms
      were available in 24 cases, covering followup intervals of between 3 and 30
      years, and suitable for individual statistical analysis in 16 cases: 14 cases
      also had MRI findings. Significant progression in hearing impairment was found in
      10 cases, while findings of significant fluctuation were made in seven cases.
      These findings did not clearly correlate with MRI findings. Substantial
      fluctuation occurred only in cases followed at a relatively young age. Patients
      with an enlarged endolymphatic duct and/or sac showed significantly higher
      sensorineural hearing thresholds than those with either normal MRI findings or
      cochlear/labyrinthine hypoplasia with or without enlarged duct or sac. We
      conclude that progressive, fluctuant hearing loss occurred in some BOR patients;
      however, only young patients showed substantial threshold fluctuation. BOR
      patients with an enlarged endolymphatic duct and/or sac on MRI seemed to be
      predisposed to developing more severe hearing impairment.

PMID- 15726844
TI  - Audiological features of Turner's syndrome in adults.
AB  - Abnormalities of the ear and hearing are well recognized in Turner's syndrome
      (TS), which is one of the most common chromosomal abnormalities. Presented here
      are the preliminary data from a UK study of the audiological features of 113
      women over the age of 16 years with TS. Seventeen per cent had normal hearing.
      19% had conductive or mixed loss, and 47% had sensorineural hearing loss
      associated with the TS. The results are discussed with reference to previously
      published studies and to the lack of consensus on comparative definitional terms
      in audiology.

PMID- 15726845
TI  - Effects of exposure of the ear to GSM microwaves: in vivo and in vitro
      experimental studies.
AB  - The effects of mobile phone (GSM) microwaves on the ears of guinea pigs were
      investigated in two in vivo experiments and one in vitro experiment. In the first
      experiment, three groups of eight guinea pigs had their left ear exposed for 1
      h/day, 5 days/week, for 2 months, to GSM microwaves (900 MHz. GSM modulated) at
      specific absorption rates (SARs) of 1, 2 and 4 W/kg respectively, and a fourth
      group was sham-exposed. Distortion-product otoacoustic emissions (DPOAEs) were
      measured for each ear before exposure, at the end of the 2-month exposure period,
      and 2 months later. In the second experiment, the same protocol was applied to
      eight sham-exposed and 16 exposed guinea pigs at 4W/kg, but the auditory
      brainstem response (ABR) thresholds were monitored. Repeated-measures ANOVA
      showed no difference in DPOAE amplitudes or in ABR thresholds between the exposed
      and non-exposed ears and between the sham-exposed and exposed groups In the
      course of the second experiment, acute effects were also investigated by
      measuring once, in all animals, ABR thresholds just before and just after the 1-h
      exposure: no statistically significant difference was observed. In vitro, the two
      organs of Corti (OCs) of newborn rats (n=15) were isolated and placed in culture.
      For each animal, one OC was exposed for 24-48 h to 1 W/kg GSM microwaves, and the
      other was sham-exposed. After 2-3 days of culture, all OCs were observed under
      light microscopy. They all appeared normal to naive observers at this stage of
      development. These results provided no evidence that microwave radiation, at the
      levels produced by mobile phones, caused damage to the inner ear or the auditory
      pathways in our experimental animals.

PMID- 15726846
TI  - Early function of splinted implants in maxillas and posterior mandibles, using
      Branemark System Tiunite implants: an 18-month prospective clinical multicenter
      study.
AB  - BACKGROUND: Immediate or early loading of implants placed in maxillas and
      posterior mandibles has been a concern as bone density is often low in these
      areas, making it difficult to establish good initial implant stability. By
      adapting implant design and insertion protocols, however, high initial implant
      stability may be achieved in these regions. Further, a modified implant surface
      texture has been proved to help in maintaining stability during the initial
      healing period. PURPOSE: The aim of the present study was to investigate the
      clinical performance of oxidized titanium implants (TiUnite, Nobel Biocare AB,
      Gothenburg, Sweden) when used for early function in the maxilla and in the
      posterior mandible, locations where the bone density often is low. A further aim
      was to evaluate the marginal bone level at oxidized implants and compare it with
      that of machined-surface implants used in a previous study. MATERIALS AND
      METHODS: Thirty-one patients were consecutively included in the study, and 37
      edentulous areas in maxillas and posterior mandibles were treated. Bruxism and
      uncontrolled periodontal disease were exclusion criteria. Temporary prostheses
      were generally placed within 9 days but not after 16 days from implant placement.
      A previous study applying the same study design and clinical protocol but using
      machined-surface implants was used for comparisons. RESULTS: Of the 111 implants
      installed, 1 failed, giving an overall survival rate of 99.1% after 18 months.
      The prosthesis survival was 100%. The marginal bone resorption was 0.8 mm
      (standard deviation [SD], 1.0), as opposed to 1.6 mm (SD, 1.3) in the previous
      study with machined-surface implants, but was not statistically significantly
      different (p = .10). CONCLUSION: The present clinical protocol (aiming at high
      primary stability) and the use of oxidized titanium implants for early functional
      loading in the maxilla and the posterior mandible resulted in a high implant
      survival rate and a favorable marginal bone level during a follow-up of 18
      months. The difference in marginal bone resorption between the oxidized implants
      in the present study and the machined implants from a previous investigation with
      the same study design was not statistically significant.

PMID- 15726848
TI  - Provisional implants: a clinical prospective study in 45 patients, from implant
      placement to delivery of the final bridge.
AB  - BACKGROUND: Protocols for submerged healing of dental implants often require the
      patient to have no teeth until suture removal and to wear a removable prosthesis
      during the remaining healing period. This may be inconvenient for the patient,
      and healing may be influenced negatively by the removable prosthesis. PURPOSE:
      The aim of the present prospective clinical study was to evaluate the use of
      provisional implants (PIs) to provide patients with a provisional fixed bridge
      during the healing of permanent implants. MATERIALS AND METHODS: Twenty female
      and 25 male patients were consecutively included in the study. The 45 patients
      were treated for either partial (16 patients) or total (29 patients) edentulism
      in the maxilla. The permanent implants were placed first; as many PIs as possible
      were then installed between the permanent implants. After suturing, impressions
      from which to manufacture provisional bridges (to be cemented to the PIs) were
      taken. The patients were monitored with clinical and radiographic follow-up from
      implant placement to delivery of the final prosthesis. RESULTS: Five (2.2%) of
      the 230 permanent Branemark System implants (Nobel Biocare AB, Gothenburg,
      Sweden) did not integrate. None of the failures could be related to the presence
      of PIs between the permanent implants. Seven PIs failed during the observation
      period. In addition, 17 (9%) of the 192 PIs showed mobility at the second-stage
      surgery although they had supported the provisional bridges without clinical
      symptoms. Forty-four of 45 patients showed stabile PI bridges at the time of
      second-stage surgery. CONCLUSION: Based on our experiences we concluded that
      provisional implants can be successfully used to provide patients with a fixed
      provisional bridge during the healing of permanent implants.

PMID- 15726847
TI  - A three-year follow-up report of a comparative study of ITI Dental Implants and
      Branemark System implants in the treatment of the partially edentulous maxilla.
AB  - BACKGROUND: Many longitudinal studies of different implant systems have been
      published but few controlled randomized investigations have been reported. A 1
      year report of a comparative study of ITI Dental Implant System implants
      (Straumann AG, Waldenburg, Switzerland) and Branemark System implants (Nobel
      Biocare AB, Gothenburg, Sweden) has been published by the present authors. This
      paper is a 3-year follow-up of that randomized study. PURPOSE: The aim of the
      study was to compare the outcome of fixed partial prostheses supported by ITI or
      Branemark implants. The outcome was evaluated primarily in terms of survival
      rates and changes in marginal bone level. MATERIAL AND METHODS: The study group
      comprised 28 patients with anterior residual dentition in the maxilla. The
      patients were provided with two to four implants on each side of the dentition
      and were randomly allocated to Branemark implants or ITI implants; 77 ITI
      implants and 73 Branemark implants were inserted. After 6 months abutment
      connections were made to both ITI and Branemark implants. All patients were
      provided with fixed partial prostheses of gold-ceramic. The patients were
      followed up annually with clinical and radiographic examinations for 3 years
      RESULTS: Two Branemark implants and two ITI implants were lost. The Branemark
      implants were lost before loading whereas the ITI implants were lost because of
      periimplantitis. The survival rate for both groups was 97.3%. The mean marginal
      bone level of the Branemark implants was situated 1.8 mm from the reference point
      at both the baseline and the 3-year examinations. The corresponding values for
      the ITI implants were 1.4 mm at baseline and 1.3 mm after 3 years. There was no
      significant difference between the implant systems with regard to bone level or
      bone level change. A steady state of the marginal bone level was calculated to
      have been reached after 3 years for 95.5% of the Branemark implants and 87.1% of
      the ITI implants. Periimplantitis (infection including pus and bone loss) was
      observed with seven ITI implants but with none of the Branemark implants. This
      difference was statistically significant. CONCLUSIONS: No statistically
      significant differences were found between the implants studied, except for the
      frequency of periimplantitis, which was higher for the ITI implants. The survival
      rates were high, and the marginal bone loss was small for both systems.

PMID- 15726849
TI  - Interimplant distance and crestal bone resorption: a histologic study in the
      canine mandible.
AB  - BACKGROUND: Crestal bone loss has been shown to occur around dental implants.
      This crestal bone resorption may determine a more apical position of the gingival
      margin. A clear trend of increased bone loss with increased interimplant distance
      has been reported. PURPOSE: The aim of the present study was to evaluate, in the
      canine mandible, the crestal bone behavior around dental implants inserted with
      different interimplant distances. MATERIALS AND METHODS: Sandblasted and acid
      etched implants (Bone System, Milano, Italy) were placed in the mandibles of six
      beagle dogs. Each dog received 10 implants in the mandible (five in the right
      side and five in the left side). A total of 60 implants was used in this study.
      The implants were divided in four groups: group I, with a 2 mm interimplant
      distance; group II, with a 3 mm interimplant distance; group III, with a 4 mm
      interimplant distance; and group IV, with a 5 mm interimplant distance. The dogs
      were killed after 12 months. RESULTS: No statistically significant differences
      were found in regard to vertical bone loss whereas on the contrary, statistically
      significant differences were found in regard to lateral bone loss (p = .0001).
      Statistically significant differences also were found in regard to vertical
      crestal bone loss (p = .0001). In fact vertical crestal bone loss decreased, from
      1.98 mm in group I to 0.23 mm in group IV. CONCLUSIONS: The clinical significance
      of these data lies in the fact that the increased crestal bone loss results in an
      increase in the distance between the base of the contact points of the
      neighboring implants and the crest of bone, and this fact could determine whether
      the papilla is present or absent between two implants.

PMID- 15726850
TI  - Abutment screw loosening and bending resistance of external hexagon implant
      system after lateral cyclic loading.
AB  - BACKGROUND: Rigorous efforts to reduce the recurrence of abutment screw loosening
      in single-tooth implant restorations have recently been made. However, the
      behavior of the implant/abutment joint components with respect to critical
      bending force is still unclear. PURPOSE: This study investigated the effect of
      different cyclic loading periods on abutment screw loosening and bending
      resistance of a single-tooth external hexagon implant system. MATERIAL AND
      METHODS: Fifteen Branemark implant assemblies were divided equally into groups A,
      B, and C. Each assembly consisted of a Branemark System Mk IV 4 x 10 mm implant
      (Nobel Biocare AB, Gothenburg, Sweden) mounted in a brass block, a CeraOne 3 mm
      abutment (Nobel Biocare AB), and an experimental cement-retained superstructure.
      For groups A and B a cyclic load of 50 N was applied centrally and perpendicular
      to the long axis of the implant. Targets of 1.0 x 10(6) cycles (40 months of
      simulated function) and 0.5 x 10(6) cycles (20 months of simulated function) were
      defined for groups A and B, respectively. Group C (control) was left unloaded for
      the same loading time period as was group B. Reverse torque was recorded before
      and after loading, and the difference was calculated. After cyclic loading,
      specimens were mounted in a testing machine, and the yielding and bending
      strengths were measured. The data were analyzed with one-way analysis of variance
      and were compared by means of the Tukey test (p < .05). RESULTS: There were
      statistically significant differences (p < .001) in the reverse torque difference
      values of group A ([-5.6 to -3.4] +/- 0.86 Ncm) as compared to those of group B
      ([-2.4 to -1.6] +/- 0.32 Ncm) and group C ([-0.7 to 0.0] +/- 0.26 Ncm). Likewise,
      group B showed a significant difference compared to group C (p = .002). On the
      other hand there was no statistically significant difference in the mean values
      among the test groups in regard to the yielding and bending strengths (p >.050).
      CONCLUSION: Within the limitations of this study, long-term fatigue significantly
      affected the reverse torque values under centric lateral load (p <.001) whereas
      it had no significant effect on the resistance of the implant/abutment joint to
      static bending.

PMID- 15726851
TI  - Bone reformation with sinus membrane elevation: a new surgical technique for
      maxillary sinus floor augmentation.
AB  - BACKGROUND: Various maxillary sinus floor augmentation techniques using bone
      grafts and bone substitutes are frequently used to enable placement of dental
      implants in the posterior maxilla. A previous case report demonstrated the
      possibility of promoting bone formation in the sinus by lifting the membrane
      without using a grafting material. However, the predictability of the technique
      is not known. PURPOSE: The aim of this study was to investigate whether sinus
      membrane elevation and the simultaneous insertion of titanium implants without
      additional grafting material constitute a valid technique for bone augmentation
      of the maxillary sinus floor. MATERIALS AND METHODS: The study group comprised 10
      patients in whom a total of 12 maxillary sinus floor augmentations were
      performed. A replaceable bone window was prepared in the lateral sinus wall with
      a reciprocating saw. The sinus membrane was dissected, elevated superiorly, and
      sutured to the sinus wall to create and maintain a compartment for blood clot
      formation. One to three dental implants were inserted through the residual bone
      and protruded at least 5 mm into the maxillary sinus. The bone window was
      replaced and secured with the overlying mucosa. Bone height was measured directly
      at each implant site at the time of insertion. Resonance frequency analysis (RFA)
      was performed on each implant at the time of initial placement, at abutment
      surgery, and after 12 months of functional loading. Computed tomography (CT) was
      performed in the immediate postoperative period and 6 months later, prior to
      exposure of the implants. RESULTS: A total of 19 implants (Branemark System,
      TiUnite, Nobel Biocare AB, Gothenburg, Sweden) in lengths of 10 to 15 mm were
      placed, with an average residual bone height of 7 mm (range, 4-10 mm). All
      implants remained clinically stable during the study period. Comparisons of pre-
      and postoperative CT radiography clearly demonstrated new bone formation within
      the compartment created by the sinus membrane elevation procedure. RFA
      measurements showed mean implant stability quotient values of 65, 66, and 64 at
      placement, at abutment connection, and after 12 months of loading, respectively.
      CONCLUSIONS: The study showed that there is great potential for healing and bone
      formation in the maxillary sinus without the use of additional bone grafts or
      bone substitutes. The secluded compartment created by the elevated sinus
      membrane, implants, and replaceable bone window allowed bone formation according
      to the principle of guided tissue regeneration. The precise mechanisms are not
      known, and further histologic studies are needed. Sinus membrane elevation
      without the use of additional graft material was found to be a predictable
      technique for bone augmentation of the maxillary sinus floor.

PMID- 15726852
TI  - Clinical performance of a method for the fabrication of implant-supported
      precisely fitting titanium frameworks: a retrospective 5- to 8-year clinical
      follow-up study.
AB  - BACKGROUND: The CrescoTi Precision (CTiP) method (CrescoTi Systems, Lausanne,
      Switzerland) has been introduced as an alternative method for the fabrication of
      precisely fitting titanium frameworks. The method is supposed to be used with all
      major implant systems, without the need for abutments. PURPOSE: The objectives of
      this clinical and radiographic retrospective follow-up study were to report the
      clinical performances of "CTiP-fabricated" frameworks that are screw retained
      directly to Branemark implants as opposed to Branemark implant/abutment
      assemblies (Nobel Biocare AB, Gothenburg, Sweden) and to compare the clinical
      outcomes of these two modalities. MATERIALS AND METHODS: Thirty-six patients were
      provided with 46 fixed prostheses supported by 207 Branemark regular-platform
      implants. Twenty-seven prostheses were placed on implant/abutment assemblies, and
      19 were placed directly at "implant level." The prostheses had been in function
      for 5 to 8 years at the time of the final examinations. RESULTS: Three patients
      did not attend the final examination. All 43 prostheses in the 33 examined
      patients were still in function. No major mechanical framework complications were
      observed during the observation period. One implant was lost after loading. There
      was no difference in bone loss around the abutment-free implants when compared
      with the implants provided with abutments. CONCLUSIONS: This long-term clinical
      test demonstrated that the CTiP technology constitutes a reliable prosthetic
      treatment concept in combination with Branemark implants. The results also
      revealed that the frameworks could be connected directly to the implants without
      any negative consequences.

PMID- 15726853
TI  - How do the Do Not Resuscitate-Comfort Care (DNRCC) and the Do Not Resuscitate
      Comfort Care Arrest (DNRCC-Arrest) protocols differ?

PMID- 15726854
TI  - Sex disparity in the management of dyslipidemia among patients with type 2
      diabetes mellitus in a managed care organization.
AB  - OBJECTIVE: To determine whether there were sex-related differences in the
      management of dyslipidemia among managed care enrollees with diabetes mellitus.
      STUDY DESIGN AND METHODS: Retrospective analyses were conducted using medical and
      pharmacy claims data from a health maintenance organization during 2000 and 2001.
      Patients with type 2 diabetes mellitus were identified through a validated
      algorithm of medication and diagnosis codes. Chi-squared analysis was used to
      determine if women were less likely than men to receive a lipid test or a lipid
      modifying drug. Logistic regression models were constructed to compare sex
      related differences while controlling for age, cardiovascular disease diagnosis,
      and 2 proxies of illness severity (hospitalization in 2000 and the intensity of
      diabetes mellitus drug therapy). RESULTS: During 2000 and 2001, 79.4% of women
      received a lipid test compared with 84.2% of men (chi2 = 6.69, P = .01). Also,
      33.2% of women received a lipid-modifying drug compared with 45.5% of men (chi2 =
      27.31, P < .01). Logistic regression analysis revealed that men were more likely
      than women to receive a lipid test when controlling for age, cardiovascular
      disease diagnosis, and illness severity (odds ratio [OR], 1.45; 95% confidence
      interval, 1.13-1.81). Men were also more likely than women to receive a lipid
      modifying drug when controlling for age, cardiovascular disease diagnosis,
      illness severity, and lipid testing (OR, 1.51; 95% confidence interval, 1.22
      1.86). CONCLUSION: Women with type 2 diabetes mellitus were less likely than men
      with type 2 diabetes mellitus to receive lipid tests or lipid-modifying drugs.

PMID- 15726855
TI  - National trends in the provision of smoking cessation aids within the Veterans
      Health Administration.
AB  - OBJECTIVES: To evaluate the effectiveness of the Veterans Health Administration
      (VHA) in providing treatment for tobacco dependence, accomplished by estimating
      national trends in the number and percent of smokers receiving smoking cessation
      aids (SCAs) within the VHA, trends in SCA utilization and expenditures, and the
      impact of lifting restrictions on patient access to SCAs. STUDY DESIGN AND
      METHODS: All patients receiving an outpatient SCA prescription were identified
      within the Veterans Affairs (VA) Pharmacy Benefits Management database over a 4
      year period- October 1, 1998 (n = 61 968) to September 30, 2002 (n = 76 641).
      Smoking prevalence was based on data from the VA's 1999 Large Health Survey of
      Enrollees. A subsample of sites was classified as having restricted access to
      SCAs if patients were required to attend smoking cessation classes. Changes in
      annual SCA utilization rates and expenditures by SCA type and restriction status
      were measured to assess changes in treatment of tobacco dependence. RESULTS:
      Approximately 7% of smokers received SCA prescriptions, and SCAs accounted for
      less than 1% of the VHA's annual outpatient pharmacy budget in any given year.
      Following downward trends in the cost of 30-day SCA prescriptions, annual SCA
      expenditures per patient decreased over time. Expenditures were lower for
      restricted than unrestricted sites. More than two thirds of smokers who were
      prescribed medications received the nicotine patch, a quarter received bupropion
      sustained-release, and fewer than 10% received nicotine gum. CONCLUSIONS:
      Measures of SCA utilization and cost are low, stable, and less than the
      recommended rates in national smoking cessation guidelines, suggesting that this
      population of smokers is undertreated. Removing SCA restrictions is not
      prohibitively expensive and improves access to cost-effective care.

PMID- 15726856
TI  - A pharmacoepidemiological approach to investigating inappropriate physician
      prescribing in a managed care setting in Israel.
AB  - OBJECTIVE: To identify cases of inappropriate physician prescribing in a managed
      care setting in Israel that may have resulted from misuse of magnetic-stripe
      membership cards. STUDY DESIGN: Retrospective drug utilization analysis of
      electronic patient prescription data. METHODS: In a managed care setting
      involving approximately 1000 physicians who issue approximately 1.4 million
      prescriptions annually, the rate of prescription of sex-specific drugs to
      patients of the opposite sex for which the drugs are indicated was evaluated for
      2003. The categories of drugs included in the analysis were drugs for the
      treatment of benign prostatic hyperplasia or erectile dysfunction that were
      prescribed to women, as well as oral contraceptives, vaginal pessaries, hormone
      therapy, or raloxifene hydrochloride prescribed to men. RESULTS: Throughout the
      study year, 193 different physicians wrote 341 prescriptions that matched the
      drug inclusion criteria for 210 different patients. The most frequently observed
      scenario involved the prescription for women of selective alpha-blockers,
      including alfuzosin hydrochloride, tamsulosin hydrochloride, and terazosin
      hydrochloride, that are indicated exclusively for the treatment of benign
      prostatic hyperplasia. CONCLUSIONS: The electronic patient record system used in
      the health maintenance organization studied was programmed to block the
      prescription of sex-specific drugs for patients of the opposite sex for which
      they are intended unless proper authorization has been obtained. Furthermore,
      periodic investigation into prescription impropriety may be easily accomplished
      through the implementation of pharmacoepidemiological methods commonly used in
      drug utilization studies.

PMID- 15726857
TI  - Using a claims data-based sentinel system to improve compliance with clinical
      guidelines: results of a randomized prospective study.
AB  - OBJECTIVE: To demonstrate the potential effect of deploying a sentinel system
      that scans administrative claims information and clinical data to detect and
      mitigate errors in care and deviations from best medical practices. METHODS:
      Members (n = 39 462; age range, 12-64 years) of a midwestern managed care plan
      were randomly assigned to an intervention or a control group. The sentinel system
      was programmed with more than 1000 decision rules that were capable of generating
      clinical recommendations. Clinical recommendations triggered for subjects in the
      intervention group were relayed to treating physicians, and those for the control
      group were deferred to study end. RESULTS: Nine hundred eight clinical
      recommendations were issued to the intervention group. Among those in both groups
      who triggered recommendations, there were 19% fewer hospital admissions in the
      intervention group compared with the control group (P < .001). Charges among
      those whose recommendations were communicated were dollar 77.91 per member per
      month (pmpm) lower and paid claims were dollar 68.08 pmpm lower than among
      controls compared with the baseline values (P = .003 for both). Paid claims for
      the entire intervention group (with or without recommendations) were dollar 8.07
      pmpm lower than those for the entire control group. In contrast, the intervention
      cost dollar 1.00 pmpm, suggesting an 8-fold return on investment. CONCLUSION:
      Ongoing use of a sentinel system to prompt clinically actionable, patient
      specific alerts generated from administratively derived clinical data was
      associated with a reduction in hospitalization, medical costs, and morbidity.

PMID- 15726858
TI  - Pharmacy benefits management in the Veterans Health Administration: 1995 to 2003.
AB  - The Department of Veterans Affairs (VA) Pharmacy Benefits Management Strategic
      Healthcare Group (VA PBM) oversees the formulary for the entire VA system, which
      serves more than 4 million veterans and provides more than 108 million
      prescriptions per year. Since its establishment in 1995, the VA PBM has managed
      pharmaceuticals and pharmaceutical-related policies, including drug safety and
      efficacy evaluations, pharmacologic management algorithms, and criteria for drug
      use. These evidence-based practices promote, optimize, and assist VA providers
      with the safe and appropriate use of pharmaceuticals while allowing for formulary
      decisions that can result in substantial cost savings. The VA PBM also has
      utilized various contracting techniques to standardize generic agents as well as
      specific drugs and drug classes (eg, antihistamines, angiotensin-converting
      enzyme inhibitors, alpha-blockers, and 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors [statins]). These methods have enabled the VA to save
      approximately dollar 1.5 billion since 1996 even as drug expenditures continued
      to rise from roughly dollar 1 billion in fiscal year (FY) 1996 to more than
      dollar 3 billion in FY 2003. Furthermore, the VA PBM has established an outcomes
      research section to undertake quality-improvement and safety initiatives that
      ultimately monitor and determine the clinical impact of formulary decisions on
      the VA system nationwide. The experiences of this pharmacy benefits program,
      including clinical and contracting processes/procedures and their impact on the
      VA healthcare system, are described.

PMID- 15726860
TI  - Nurses do have an enormous amount to celebrate. Interview by Carolyn Scott.

PMID- 15726859
TI  - A user's guide to the disease management literature: recommendations for
      reporting and assessing program outcomes.
AB  - Recently there has been tremendous growth in the number of lay-press articles and
      peer-reviewed journal articles reporting extraordinary improvements in health
      status and financial outcomes due to disease management (DM) interventions.
      However, closer scrutiny of these reports reveals serious flaws in research
      design and/or analysis, leaving many to question the veracity of the claims. In
      recent years, there have been numerous contributions to the literature on how to
      assess the quality of medical research papers. However, these guidelines focus
      primarily on randomized controlled trials, with little attention given to the
      observational study designs typically used in DM outcome studies. As such,
      general guides to evaluating the medical literature are inadequate in their
      utility to assist authors and readers of DM outcomes research. The purpose of
      this paper is to provide authors with a clear and comprehensive guide to the
      reporting of DM outcomes, as well as to educate readers of the DM literature
      (both lay and peer reviewed) in how to assess the quality of the findings
      presented.

PMID- 15726861
TI  - Start the public health revolution.

PMID- 15726862
TI  - Creating a new vision for primary care.

PMID- 15726863
TI  - Keeping employer and employee happy.
AB  - There is currently significant interest in the management of chronic conditions
      such as diabetes and asthma. Despite levels of control varying according to each
      individual, generally these people manage their condition successfully and live
      normal, productive lives. The CIGNA Health Management Programme is a private
      health-care service for employees that offers benefits both to them and their
      employer. The approach has been shown to have a positive impact on employee
      attendance and productivity.

PMID- 15726864
TI  - Introducing a day-case lung biopsy service.
AB  - The change agent component of the specialist nurse role can be effective in
      service review and management. This was put into effect in one hospital to enable
      the lung biopsy service to become an efficient, high-quality patient-centred
      resource for patients who are suspected of having lung cancer.

PMID- 15726865
TI  - Avoid irritants to reduce breathlessness.

PMID- 15726866
TI  - Conservative and surgical approaches to the treatment of overactive bladder.
AB  - Overactive bladder is a prevalent and often distressing condition that has a
      significant negative effect on the quality of life of those affected. It
      contributes to the huge burden of incontinence on NHS resources. Effective
      treatment is available; however, most patients will never admit their problems,
      seek advice or be identified.

PMID- 15726867
TI  - Keeping hospitals clean: how nurses can reduce health-care-associated infection.
AB  - From modern matrons to student nurses, everyone is responsible for the
      environment in which they work. All nurses should be aware of the cleaning system
      used in their organisation and be able to follow it when necessary. A clean ward
      or clinic will help prevent hospital-acquired infections and promote patient and
      visitor confidence.

PMID- 15726868
TI  - Leg ulcer management: how addressing a patient's pain can improve concordance.
AB  - Failure to carry out a comprehensive assessment of a patient with leg ulcers will
      often delay healing owing to non-concordance with treatment. This article uses a
      case study to encourage health professionals to improve care by focusing on each
      individual patient's perspective of pain and involving patients in planning a
      care regimen.

PMID- 15726869
TI  - Initiatives to improve outcomes for chronic obstructive pulmonary disease.
AB  - Pharmacological and non-pharmacological treatments have been shown to greatly
      improve quality of life for patients with chronic obstructive pulmonary disease.
      This article looks at schemes to help professionals and patients manage this life
      threatening condition by improving symptoms and preventing exacerbations.

PMID- 15726870
TI  - A guide to wash creams.

PMID- 15726871
TI  - Finding an alternative endoscope disinfectant to glutaraldehyde.
AB  - Glutaraldehyde poses an occupational health hazard or risk for staff, with up to
      15% of UK hospitals using it as their first-choice endoscope disinfectant. One
      NHS trust yielded unexpected additional savings by introducing a safer
      alternative in a bid to reduce potential health, safety and environmental risks.

PMID- 15726872
TI  - Leading geographically dispersed teams.

PMID- 15726873
TI  - It only hurts when I laugh.

PMID- 15726874
TI  - Anti-anginal and anti-ischemic effects of the selective beta-blocker talinolol in
      patients with stable angina pectoris.
AB  - OBJECTIVE: To determine the dose dependency of the anti-anginal and antiischemic
      effects of the selective beta-blocker talinolol administered once-daily in a
      randomized, double-blind, placebo-controlled multicenter study in patients with
      stable angina pectoris. METHODS: Standardized bicycle ergometry at baseline and
      after 3 and 6 weeks of treatment was used to assess exercise capacity. The
      primary endpoint was the change in the maximum exercise time (MET) 24 +/- 1 h
      after the last intake of study medication compared to baseline. Secondary
      efficacy parameters were time to onset of angina, time to 1 mm ST segment
      depression, angina attacks, consumption of short-acting nitrates, blood pressure
      and pulse rate. Patients were randomly allocated to treatment with talinolol
      (100, 200 or 300 mg once daily) or placebo for a period of 6 weeks. RESULTS: A
      total of 241 outpatients (204 male and 37 female) aged between 34 and 83 years,
      were randomized in 31 centers in Germany, Poland and the Czech Republic. At the
      end of treatment, the primary endpoint (change in MET compared to baseline)
      showed no significant difference between the talinolol groups and placebo. The
      means of MET prolongation ranged from 27.4 sec under placebo to a maximum of 47.6
      sec in the 200 mg group. However, the time to 1 mm ST segment depression during
      exercise increased markedly with talinolol, the difference to placebo reaching
      statistical significance with the 200 mg/d dose (80.1 +/- 32.7 sec, p = 0.0182)
      and 300 mg/d dose (82.0 +/- 31.6 sec, p = 0.0127). In the case of the other
      secondary variables, the most pronounced effects were recorded for talinolol
      doses of 200 and 300 mg/d. Talinolol significantly inhibited the exercise-induced
      increase in heart rate and blood pressure. The decrease in rate pressure product
      at 100 W workload was statistically significant with all administered talinolol
      doses (delta from baseline to final visit 3090, 4351 and 4291 for 100, 200 and
      300 mg/d, respectively, p < 0.0001). Despite once-daily dosing, talinolol at
      doses up to 300 mg/d was very well tolerated. No unexpected adverse drug
      reactions were observed. CONCLUSION: The results show that talinolol administered
      once daily in a dosage of 200 - 300 mg/d is effective and safe in the management
      of chronic stable angina.

PMID- 15726875
TI  - Benfotiamine in the treatment of diabetic polyneuropathy--a three-week
      randomized, controlled pilot study (BEDIP study).
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy of benfotiamine
      administered over three weeks (allithiamine; a lipid-soluble vitamin B1 prodrug
      with high bioavailability) to patients with diabetic polyneuropathy in a
      randomized, placebo-controlled, double-blind, two-center pilot study. MATERIAL
      AND METHODS: Forty inpatients (23 male, 18 female, age range 18 - 70 years) with
      a history of type 1 or 2 diabetes and polyneuropathy of not longer than two
      years, were included in the study. Twenty Patients received two 50 mg
      benfotiamine tablets four times daily and 20 patients received placebo over the
      three-week study period. Two clinical units were involved with 10 patients
      receiving placebo and 10 patients benfotiamine in each. The neuropathy score
      according to Katzenwadel et al. [1987] was used to evaluate symptoms of
      polyneuropathy, vibration perception threshold and both the physician's and the
      patient's own assessment were documented. RESULTS: A statistically significant (p
      = 0.0287) improvement in the neuropathy score was observed in the group given
      active drug when compared to the placebo-treated controls. There was no
      statistically significant change observed in the tuning fork test. The most
      pronounced effect on complaints was a decrease in pain (p = 0.0414). More
      patients in the benfotiamine-treated group than in the placebo group considered
      their clinical condition to have improved (p = 0.052). No side effects
      attributable to benfotiamine were observed. The differences between the groups
      cannot be attributed to a change in metabolic parameters since there were no
      significant alterations in the HbA1 levels and blood sugar profiles. The body
      mass index of the two groups did not differ. CONCLUSION: This pilot investigation
      (BEDIP Study) has confirmed the results of two earlier randomized controlled
      trials and has provided further evidence for the beneficial effects of
      benfotiamine in patients with diabetic neuropathy.

PMID- 15726876
TI  - Duloxetine pharmacokinetics in cirrhotics compared with healthy subjects.
AB  - OBJECTIVE: To compare the pharmacokinetics of single-dose duloxetine in cirrhotic
      and healthy subjects. METHODS: An open-label inpatient study compared duloxetine
      pharmacokinetics in six subjects with moderate liver cirrhosis (Child-Pugh class
      B) to those in six healthy subjects. Subjects received a single 20 mg capsule of
      duloxetine following overnight fasting. Blood samples were collected up to 120 h
      post dose for determination of plasma concentrations of duloxetine and its major
      metabolites using a validated LC/MS/MS method. Plasma concentration-time data for
      duloxetine and its major metabolites were analyzed by noncompartmental methods.
      Specific pharmacokinetic parameters were assessed statistically using a mixed
      effects model. RESULTS: Duloxetine apparent clearance was significantly lower (24
      vs 160 l/h, p < 0.05) and AUC values were substantially higher (775 vs 268 ng x
      (h/ml) in cirrhotic compared to healthy subjects. The half-life of duloxetine was
      about three times longer (47.8 vs 13.5 h) in cirrhotic than in healthy subjects
      (p < 0.05). In contrast, there was no significant difference in Cmax or apparent
      volume of distribution between the two groups. The metabolites exhibited lower
      levels and longer half-lives in cirrhotic subjects compared to healthy subjects.
      The lower clearance and slower elimination of duloxetine in cirrhotic individuals
      is likely attributable to impaired duloxetine metabolism. CONCLUSIONS: The rate
      of duloxetine elimination is reduced for cirrhotic subjects, making dosage
      adjustments appropriate. Based on simulations, the duloxetine dose for at least
      an initial treatment period may need to be reduced and/or less frequently
      administered for patients with moderate cirrhosis.

PMID- 15726877
TI  - Pharmacokinetics of prednisolone in man during acute and chronic exposure to high
      altitude.
AB  - INTRODUCTION: The exposure to high altitude (H) produces several physiologic
      alterations which may induce changes in the pharmacokinetics of drugs. This
      hypothesis has been confirmed in previous studies which suggest that drugs which
      are highly bound to plasma proteins are most likely to exhibit altered
      pharmacokinetics. OBJECTIVES: To further elucidate the influence of H on
      pharmacokinetics, prednisolone was selected, since it is highly bound to plasma
      proteins, renally excreted and poorly bound to red blood cells. SUBJECTS,
      MATERIALS AND METHODS: Prednisolone (80 mg) was given orally to three groups of
      young healthy volunteers. One group was residing at sea level (L): the same
      volunteers were studied again after 15 hours of exposure to high altitude (3600
      m, HA group), and volunteers living at H for at least six months (group HC).
      RESULTS: There were no statistically significant differences in the
      pharmacokinetic parameters calculated from plasma data in the three situations
      studied. When calculated from whole blood data, however, AUC and Cmax were
      increased and both volume of distribution and clearance diminished after exposure
      to H, either acute or chronically. Binding to proteins increased significantly
      after H exposure from 57% in group L to 75% and 94% in group H and HC,
      respectively. Binding to erythrocytes also increased with H exposure from 43.7%
      in group L to 50.6% and 61.6% in group HA and HC, respectively. The
      prednisolone/prednisone ratio in urine was 11.1 in group L, 7.3 in group HA and
      45.6 in group HC. CONCLUSION: Since prednisone has very little intrinsic
      glucocorticoid activity and has to be converted to prednisolone for therapeutic
      effect, the alteration of the prednisolone/prednisone ratio, as a result of high
      altitude exposure could be clinically relevant. Additional experiments are
      desirable to further evaluate this observation.

PMID- 15726878
TI  - Attenuation of the kaluretic properties of furosemide by triamterene (Dyrenium)
      in healthy volunteers.
AB  - OBJECTIVE: To examine if concomitant administration of furosemide, a loop
      diuretic, with the potassium- and magnesium-sparing diuretic triamterene would
      decrease loss of potassium and magnesium while improving diuresis. METHODS: In
      this open-label, three-way crossover study, healthy subjects were randomized to
      receive treatment with 40 mg furosemide, with 150 mg triamterene, or treatment
      with 40 mg furosemide and 150 mg triamterene. Urine samples were collected 24
      hours before dosing and between 0 - 1, 1 - 2, 2 - 3, 3 - 4, 4 - 6, 6 - 8, 8 - 12,
      and 12 - 24 hours post-dosing. Sodium and potassium levels were measured by an
      ion-selective electrode method. Magnesium was measured colorimetrically using a
      xylidyl blue reaction. RESULTS: Co-administration of furosemide with triamterene
      resulted in enhanced diuresis, particularly in the first 0 - 12 hours post-dose,
      compared with either furosemide or triamterene alone. Compared to individual
      treatments, combination therapy significantly increased urinary sodium excretion
      (p = 0.0001) while significantly decreasing urinary potassium excretion (p =
      0.0001); importantly, the magnesium-sparing characteristic of triamterene was
      retained with furosemide co-administration. CONCLUSION: Triamterene, when used in
      combination with the loop diuretic, furosemide, preserves intracellular potassium
      and magnesium while enhancing the natriuretic effect of furosemide.

PMID- 15726879
TI  - Propranolol increases the complexity of heart rate fluctuations--a mode of
      antiarrhythmic action?
AB  - OBJECTIVE: To study the beta-blocking effect of propranolol on heart rate and
      arterial blood pressure fluctuations in healthy subjects using linear methods and
      a set of nonlinear models. METHODS: In a randomized, double-blind, placebo
      controlled study, healthy young adults received a 40 mg oral dose of propranolol
      (n = 12) or placebo (n = 12). The effects of propranolol and placebo were
      assessed using time series of the RR interval (RRI) and systolic arterial blood
      pressure (SAP) obtained from continuous ECG and blood pressure signal recordings.
      Heart rate and systolic arterial blood pressure fluctuations were analyzed using
      nonlinear and linear methods of time series statistics. RESULTS: Propranolol
      significantly increased the complexity of heart rate fluctuations in terms of
      symbol dynamic (SymDyn) entropy and symbol dynamic percentage of forbidden words.
      Propranolol augmented cross entropy between RRI and SAP and increased fractal
      dimension of RRI. beta-blockade also affected linear measures of RRI fluctuations
      by increasing parasympathetic, respiration-related high-frequency (HF)
      variability and arterial baroreflex-related low-frequency (LF) variability.
      Propranolol administration, however, had no effect on the complexity of SAP
      fluctuations assessed using nonlinear time series statistics. CONCLUSIONS: beta
      blockade by propranolol has a differential effect on RRI and SAP fluctuations in
      healthy subjects. Propranolol increases the complexity of RRI fluctuations. The
      effect is associated with the cardiac vagotonic drug action of propranolol. SAP
      fluctuations are almost unchanged. The increased complexity of RRI fluctuations
      may be a beneficial feature of beta-blockade, since many cardiovascular diseases
      decrease the complexity of RRI time series by dampening cardiovascular reflex
      actions.

PMID- 15726880
TI  - Simultaneous itraconazole bioequivalence assessment and CYP3A phenotyping in
      South American subjects.
AB  - OBJECTIVE: The present study evaluates the acute effect of a single-dose
      itraconazole administration on CYP3A phenotype, as measured by cortisol MR ratio
      in urine. METHODS: Twenty-four healthy Uruguayan subjects recruited according to
      strict inclusion criteria participated in an open-label, randomized, two-period,
      crossover study designed to evaluate the bioequivalence of an itraconazole
      formulation (Traconal 100 mg, Ache Labs, Sao Paulo, Brazil). The study comprised
      two treatment periods separated by a wash-out period of 14 days. In each period a
      series of venous blood samples were drawn over 48 hours. Three urine samples were
      obtained for CYP3A phenotyping: pre-dose, 24 and 48 hours after dosing. Blood and
      urine samples were assayed for itraconazole, beta-hydroxycortisol and cortisol
      using a validated chromatographic method. RESULTS: The ratio of the mean AUC0
      inf. T/AUC0-inf. R was included in the bioequivalence range, however, due to high
      variability, the CI90% was not. It was found that the cortisol metabolic ratio
      (MR) showed inhibition relative to basal activity in a proportion of subjects 24
      hours (68 +/- 6.1%, mean +/- CI95%) and 48 hours (80 +/- 7.3%, mean +/- CI95%)
      after ingestion of itraconazole. A significant correlation was found between
      itraconazole AUC0-inf. and normalized basal CYP3A MR for the reference (r = 0.62,
      t = 3.72, p = 0.001) and the test product (r = 0.74, t = 5.22, p = 0.00003). A
      good correlation existed between basal cortisol MR and the elimination half-life
      of itraconazole. CONCLUSIONS: The findings are in line with the hypothesis that
      the determination of the bioavailability of highly variable CYP3A substrates
      might be improved by simultaneous non-interfering phenotyping. If this is
      confirmed, a new methodological paradigm may need to be developed in order to
      take account of metabolic variability in bioequivalence evaluation of this group
      of drugs.

PMID- 15726881
TI  - Metabolic and pharmacokinetic evaluation of a novel 3-hydroxypyridinone iron
      chelator, CP502, in the rat.
AB  - A recently synthesized 3-hydroxypyridinone derivative with an amido function at
      the 2-position, CP502 (1,6-dimethyl-3-hydroxy-4-(1H)-pyridinone-2-carboxy-(N
      methyl)-amide hydrochloride), exhibited high in vitro iron chelating potency
      (pFe3+ =21.7). It was targeted as a new iron-chelating candidate for further
      development in early pre-clinical testing. To evaluate its pharmacokinetics,
      including oral bioavailability, metabolic and disappearance profiles, studies
      were conducted in Sprague Dawley male rats. A single 150 mg/kg intravenous and
      oral dose was given to male Sprague Dawley rats (N=6, B.Wt. 250g). The rats were
      placed in metabolic cages and fasted overnight before the dosing. Venous blood
      samples (200 microL per withdrawal) were collected at defined time points before
      (blank) and up to 28 h post administration. Urine and feces were collected before
      dosing (blank) and in 24 h intervals up to 72 h post administration. Plasma CP502
      concentration versus time profiles were consistent with two-compartment
      distribution, and the oral bioavailability approached 100%. Total clearance and
      mean residence time (i.v.) were 1.02 L/kg/h and 1.10 h, respectively.
      Simultaneous computer fitting yielded V1 and Vss estimates of 0.96 L/kg and 1.74
      L/kg, respectively. CP502 was mainly excreted unchanged via urine (45.29+/-9.40 %
      of total dose) or as glucuronide (6.46+/-1.22% of total dose). High iron
      chelation potential and favorable pharmacokinetic and metabolic profiles indicate
      that CP502 is a promising candidate for further development.

PMID- 15726882
TI  - Pharmacokinetics and dialysability of naltrexone in patients undergoing
      hemodialysis.
AB  - The disposition of naltrexone (NLT) (REVIA), an opioid antagonist intended for
      patients with impaired renal function and with severe intractable itching
      refractory to regular antipruritic therapy, was characterized. Hemodialysis
      effects on both efficacy and elimination of NLT also were assessed. We developed
      a simple, sensitive and selective reverse-phase high-performance liquid
      chromatographic (HPLC) method for measuring NLT plasma concentration in
      hemodialysis patients treated to relieve pruritus. NLT and the internal standard,
      naloxone (NLX) were extracted from plasma using a solid-phase extraction method
      with sep-pack C18 cartridge. The method was employed to determine both naltrexone
      pharmacokinetics and dialysability parameters during 4-h in dialyzed patients
      with chronic renal impairment. Thus, seven patients (2 men, 5 women) with end
      stage renal disease and pruritus on regular hemodialysis were included. They
      received one tablet of NLT (Revia, 50 mg) orally prior dialysis session. The Cmax
      at the inlet and at the outlet the dialyzer were higher (255+/-117 ng/mL and
      206+/-137 ng/ml respectively) in comparison with healthy subjects (9 - 44 ng/mL).
      The decrease hepatic first-pass metabolism of NLT consecutive to end-stage renal
      disease and the renal impairment could explain the increased levels of the drug
      in plasma. Tmax before and after dialysis plates remain unchanged as healthy
      subjects (approximately 1h). With regard to dialysability, a high dialyzer
      extraction ratio averating 30 % was found with a low dialysis clearance of
      58.70+/-17 mL/min. The amount removed by dialysis is only 1.27 mg. We concluded
      that hemodialysis has little effect on NLT blood levels, and consequently on drug
      pharmacokinetics, when the drug is delivered to dialyzed patients following oral
      route. Thus, dosage adjustement is not required in the presence of advanced
      dialysis-dependant renal failure. In patients with end-stage renal disease,
      hemodialysis does not result in clinically significant alterations in the
      disposition of NLT. Post-dialysis supplementation is not required. These data
      suggest that there is no pharmacokinetic basis for modification of the initial
      dosage, but in view of NLT plasma concentration levels in the patients, a
      clinician could determine whether dosage adjustment are necessary and, if so,
      make the required calculations accurately.

PMID- 15726884
TI  - The normalization of total clearances for intravenous injection drugs.
AB  - There have been reports wherein the total clearance of certain drugs exceeded the
      blood flow rate when blood concentration data following an intravenous injection
      was used. It is theoretically unusual that for drugs carried to the tissue by
      blood, the quantity eliminated is larger than the quantity carried. Nevertheless,
      the problem about total clearance still needs to be solved. The present paper
      proposes an equation to ensure that such unusual values do not arise.

PMID- 15726883
TI  - Light induced changes in quinolone levels in rat serum and tissues.
AB  - Circadian rhythm may induce alterations of the pharmacokinetic properties of
      several drugs in clinical use. The aim of the study was to investigate whether
      lighting conditions alter the quinolone (pefloxacin) levels in serum and tissues
      and to determine any accumulation of the drug in the skin. Thirty male Wistar
      rats were divided into groups A, B, C, (n=10). The animals of group A were housed
      under 12h light/12h dark conditions, group B under 24h UV and group C was kept in
      complete darkness. All animals received 5 doses of 11mg/Kg pefloxacin every 8h
      for 48h.Pefloxacin levels were determined in serum, skin and femur by the
      inhibition zone in E.coli. in vitro. Pefloxacin concentrations in serum were
      increased in 24h darkness living status and decreased in 24h UV conditions as
      compared to group A animals. Additionally, both skin and femur pefloxacin levels
      were decreased under dark and UV conditions. In conclusion total light as well as
      total dark exposure may lead to pefloxacin pharmacokinetic changes which may have
      implications in the effectiveness of the drug in tissues.

PMID- 15726885
TI  - The stability studies and in vitro hepatic microsomal metabolism of some alpha
      phenyl-N-substituted nitrones in rats.
AB  - Nitrones are a very important class of synthetic chemicals as synthetic
      intermediates, antioxidant agents, and metabolic oxidation products of secondary
      amines and imines used drug, food, cosmetic and printing industry. In the present
      study, the stability experiments and in vitro metabolism studies using rat
      microsomal preparations fortified with NADPH were carried out using three
      different alpha-phenyl-N-substituted nitrones ie alpha-phenyl-N-tert-butylnitrone
      (PTBN), alpha-(2,6-dichlorophenyl)-N-phenylnitrone (DCPPN) and alpha-phenyl-N
      adamantanylnitrone (PADN). The separation of these compounds from the potential
      degradation, isomerization and metabolic products were performed using a reverse
      phase HPLC system with a diodearray uv detection. Following stability experiments
      at 37 degrees C using methanolic nitrone solutions, it was observed that PTBN
      produced trace amounts of benzaldehyde and the corresponding amide. DCPPN also
      produced trace amounts of amide. After 12 hours, the amount of the amide
      significantly increased. PADN produced trace amount of benzaldehyde but not any
      amide. The proposed compounds were incubated with rat microsomal preparations
      fortified with NADPH, extracted into dichloromethane (DCM) and finally evaporated
      under nitrogen in the dark conditions. PTBN was metabolized into corresponding
      amide whereas DCPPN and PADN did not. With all of the substrates, the
      corresponding aldehydes are observed with both test and control tubes using
      denaturated microsomes and without co-factors.

PMID- 15726886
TI  - In vitro microsomal [correction of mircosomal] metabolism of N-benzyl and N
      benzoylnornicotine derivates by rat.
AB  - The in vitro hepatic microsomal metabolism of N-1'-benzylnornicotine, N-l'-(p
      chlorobenzyl)nornicotine, N-1'-benzoylnornicotine and N-1'-(p-chlorobenzoyl)
      nornicotine was studied using hepatic washed rat microsomal preparations
      fortified with NADPH. Substrates and their potential metabolites were
      synthesized, characterised by spectral methods, and separated using a reverse
      phase HPLC system consisted of a C18 column and a mobile phase composition of
      acetonitrile: phosphate buffer. Substrates and their potential metabolites were
      extracted from biological systems with dichloromethane. Metabolites detected were
      compared with retention times and uv spectra of authentic standards. Metabolic
      experiments indicated that oxidative dealkylation leading to the formation of
      nornicotine and the corresponding aldehydes was a major route of metabolism for N
      alkylnornicotine substrates. In addition, N-1'-(p-chlorobenzyl)nornicotine
      produced the corresponding lactam and amide metabolites. N-Acylnornicotines were
      hydrolysed to nornicotine.

PMID- 15726887
TI  - Human hepatic metabolism of the anxiolytic agent, RWJ-51521--API-MS/MS
      identification of metabolites.
AB  - The In vitro metabolism of the anxiolytic agent, RWJ-51521 was conducted after
      incubation with human hepatic S9 fraction in the presence of an NADPH-generating
      system. Unchanged RWJ-51521 (30% of the sample) and a total of 11 metabolites
      were profiled, quantified, and tentatively identified on the basis of API
      (ionspray)-MS/MS data. The 4 proposed metabolic pathways for RWJ-51521 are: (1)
      N/O-dealkylation, (2) phenylhydroxylation, (3) pyrido-oxidation, and (4)
      dehydration. Pathway 1 formed 2 major and 3 minor N/O-desalkyl metabolites (M1 &
      M3, 50%) and in conjunction with pathway 4, formed 2 moderate dehydrated
      metabolites (M4 & M5, 14%). Pathways 2 and 3 alone, and in conjunction with
      pathway 4, produced 4 minor metabolites (each < or =2%). RWJ-51521 is extensively
      metabolized in human hepatic S9 fraction.

PMID- 15726888
TI  - Metabolism of the new nonbenzodiazepine anxiolytic agent, RWJ-51204, in mouse,
      rat, dog, monkey and human hepatic S9 fractions, and in rats, dogs and humans.
AB  - The in vitro and in vivo metabolism of the nonbenzodiazepine anxiolytic agent,
      RWJ-51204 was investigated after incubation with mice, rat, dog, monkey, and
      human hepatic S9 fractions in the presence of NADPH-generating system, and a
      single oral dose administration to rats (100 mg/kg), dogs (5 mg/kg), and humans
      (2.5 mg/subject). Plasma and red blood cells (2 h, rat) and urine samples (0-24
      h, rat, dog and human) were obtained postdose. Unchanged RWJ-51204 (39-93% of the
      sample in vitro; < or =5% of the sample in vivo) plus 14 metabolites were
      profiled, quantified and tentatively identified on the basis of API-MS and MS/MS
      data, and by comparison of synthetic samples. The in vitro and in vivo metabolic
      pathways for RWJ-51204 are proposed, and the metabolite formations are via the
      following five pathways: 1. phenyl oxidation, 2. pyrido-oxidation, 3. N
      deethoxymethylation, 4. dehydration, and 5. glucuronidation. Pathway 1 formed 4
      hydroxy-2-fluoro-phenyl-RWJ-51204 (M1, 7-24% in vitro; 5-60% in vivo) in major
      amounts, OH-benzimidazole-RWJ-51204 (M2, 5-8% in vitro and in vivo) and diOH
      phenyl-RWJ-51204 (< or =5-16% in vitro and in vivo); in conjunction with pathway
      5 produced M1 glucuronide (60% in rat & dog; 17% in human), M2 glucuronide (16%
      in human). Pathways 2-4 formed minor/trace oxidized, and dehydrated metabolites.
      RWJ-51204 is extensively metabolized in vitro (except dog) and in vivo in rats,
      dogs and humans.

PMID- 15726889
TI  - Mechanism of the stimulatory effect of native fucoidan, highly sulfated fucoidan
      and heparin on plasminogen activation by tissue plasminogen activator: the role
      of chloride.
AB  - Native Fucoidan and unfractionated heparin enhanced by 6-fold the in vitro
      activation of human glutamic plasminogen (Glu-Plg) by tissue plasminogen
      activator (t-PA) using 0.05M Tris buffer pH 7.4, while sulfated fucoidan
      inhibited the activation under these conditions. Double reciprocal plots of these
      interactions showed that sulfated fucoidan inhibited the activation in a
      noncompetitive manner while the enhancements by heparin or native fucoidan were
      due to an increase of Vmax without affecting Km. To determine whether the
      stimulatory effect of the individual cofactor was due to its interaction with Glu
      Plg or with t-PA, experiments were performed at a fixed level of the cofactor and
      either varying in a serial fashion the concentration of Glu-Plg or of t-PA. The
      ratios of the initial rate of plasmin generation in the presence or absence of
      the cofactors were plotted against the inverse of the volume fraction of Glu-Plg
      or of t-PA. The results showed that heparin interacted with Glu-Plg while native
      fucoidan and sulfated fucoidan interacted with t-PA. Studies were also conducted
      on the effect of the two fucoidans and heparin on the activation of Glu-Plg by t
      PA using 0.05M Tris buffer pH 7.4 containing 0.1 M NaCl. Under these conditions,
      sulfated fucoidan was most effective in enhancing the activation followed by
      native fucoidan and heparin respectively. The results of this study showed that
      in presence of the buffer containing 0.1 M NaCl, heparin was interacting with t
      PA while the two fucoidans were interacting with both t-PA and Glu-Plg. A
      comparison of the double reciprocal plots of the rate of enhancement by the
      cofactors using 0.05M Tris buffer pH 7.4 containing 0.1M NaCl or in presence of
      buffer alone showed that the cofactors were more effective using 0.05M Tris
      buffer pH 7.4 alone and that addition of NaCl to the buffer slowed down the
      reactions by decreasing Vmax without affecting Km. Circular Dichroism (CD)
      studies of Glu-Plg in the far ultraviolet (UV) range showed that addition of NaCl
      destabilized the beta sheet structure which was reversed by addition of 6
      aminohexanoic acid (6-AH) or one of the cofactors, while the near UV CD spectra
      of Glu-Plg in presence of 0.1 M NaCl was enhanced by the cofactors by increasing
      its ellipticity as reported earlier for 6-AH.

PMID- 15726890
TI  - Formaldehyde concentration in the air and in cadavers at the gross anatomy
      laboratory in Hiroshima University.
AB  - The formaldehyde concentration in the air and in various tissues of 35 human
      cadavers were measured during a gross anatomy course held at the Faculty of
      Medicine of Hiroshima University in the 2003 educational year. Atmospheric
      formaldehyde levels were 0.25-0.55 ppm and thus less than the upper limit of the
      guideline for formaldehyde exposure (0.5 ppm) set by the Japan Society for
      Occupational Health (1988) except for one out of 10 measurements. The
      formaldehyde concentrations in tissues were as follows: the lung, 0.12 +/- 0.09%
      (n=29); the liver, 0.12 +/- 0.09% (n=29); and the brachioradialis muscle, 0.11 +/
      0.09% (n=30). Considerable variation was found among the cadavers and these
      values were lower than those of Tsurumi University which provided the only other
      data (average formaldehyde concentrations ranged from 0.27 to 0.32%). At
      Hiroshima University, blood is allowed to drain during embalming, whereas it is
      not at Tsurumi University. Differences in the embalming procedure are thus
      responsible for low and fluctuating formaldehyde concentrations in cadavers at
      Hiroshima University, and it is conceivable that relatively low formaldehyde
      levels in the air result from low formaldehyde concentrations in cadavers and
      good room ventilation (10 room-air changes per hour). However, the Japanese
      Ministry of Health and Welfare recommended lower formaldehyde exposure levels
      (0.08 or 0.25 ppm) in 2002. Thus, it may be necessary to further reduce
      formaldehyde levels in the gross anatomy laboratory by means of such measures as
      neutralizing formaldehyde with ammonium carbonate; using a locally ventilated
      dissection work-table, etc.

PMID- 15726891
TI  - Effects of aged garlic extract (AGE) on colorectal adenomas: a double-blinded
      study.
AB  - Aged garlic extract (AGE) is a material that has the possibility of a cancer
      preventive effect according to epidemiologic and animal studies. In order to
      confirm the effects of AGE on colorectal adenomas, we conducted a double-blinded
      randomized study using high-AGE (AGE 2.4 ml/day) and low-AGE (AGE 0.16 ml/day)
      doses 1 groups. Fifty-one patients who were diagnosed as having colorectal
      adenomas by colonoscopy were randomly assigned to the high-AGE and low-AGE
      groups. The number and size of adenomas before intake (0 month) and 6 and 12
      months after intake were measured using colonoscopy. In 37 patients chosen as
      efficacy evaluated subjects, 47.4% (9/19) in the high-AGE and 66.7% (12/18) in
      the low-AGE group had at least one new adenoma for the first and second interval
      (0 to 12 months after intake), and its relative risk was 0.71. The decrease rate
      of at least one adenoma was 50.0% (7/14) in the high-AGE group for the second
      interval (6 to 12 months after intake), whereas there was no decrease in subjects
      in the low-AGE group (p=0.02). The difference from the base-line for total size
      of adenomas increased in the low-AGE group, whereas an increase in the high-AGE
      group was suppressed for the second interval (p=0.04). The difference from the
      base-line for the total size of adenomas in subjects who had adenomas on the base
      line increased in the low-AGE group and decreased in the high-AGE group for the
      second interval (p=0.03). The results of this study suggest the possibility of
      preventive and therapeutic effects of AGE on colorectal adenomas, though it is
      necessary to investigate these in larger-scale and longer-term trials.

PMID- 15726892
TI  - Chest wall schwannoma associated with neurofibromatosis 2--a case report.
AB  - We report a rare case of neurofibromatosis type-2 (NF-2) associated with a chest
      wall schwannoma that was initially suspected of being a breast tumor. The patient
      was a 28-year-old female who was diagnosed as having NF-2 at 19 years old. At
      that time, she noticed a mass in the upper lateral region of her left breast but
      did not have it examined. The mass grew and became painful, and she was therefore
      referred to our department. Results of the initial examination indicated the
      possibility of a breast tumor, but a diagnosis of extramammary tumor of the major
      pectoralis major muscle was made on the basis of the results of ultrasonography
      and 3-dimensional computed tomography (3D-CT). An endoscope-assisted extirpation
      of the tumor was performed. Histologically, the tumor was an Antoni type A and B
      neurilemoma and was diagnosed as a schwannoma.

PMID- 15726893
TI  - [Value of cardiac nuclear imaging in clinical care of patients with ischemic
      heart disease].
AB  - Coronary revascularization with PTCA or by means of CABG surgery is frequently
      used in the care of patients with ischemic heart disease. Before
      revascularization is performed, stress myocardial perfusion imaging may assist in
      management decisions by demonstrating the presence of myocardial ischemia and
      viability, and delineating the severity and extent of coronary artery disease.
      The presence of myocardial ischemia may provide an indication for
      revascularization, even in asymptomatic persons. The significance of equivocal
      lesions may be determined and the culprit vessel may be successfully defined by
      this radionuclide technique. Recently, the quantitative estimation of myocardial
      flow reserve with N-13 ammonia PET and the precise detection of myocardial
      viability with F-18 FDG PET have been introduced to support the limitations of
      conventional SPECT imaging. After revascularization, these radionuclide
      techniques are useful to demonstrate improvement of myocardial perfusion or flow
      reserve, and are also very important to determine restenosis after PCI and graft
      disease after CABG surgery.

PMID- 15726894
TI  - [Chest radiography based on the interlobar fissures].
AB  - Recognition of which interlobar fissure in the right lung is major or minor is
      important in chest radiography. Based on assessment of the interlobar fissure,
      the location of diseases or the degree of expansion of the lobes is
      comprehensible. As a general rule, the major fissure is not seen in normal cases.
      However, the major fissure is visualized in the presence of volume loss of the
      lower lobe. Although the medial end of the minor fissure is at the intermediate
      artery between the upper and lower lobe bronchi, that of the major fissure is
      continuous to the central portion of the mediastinum. The following cases will be
      presented: post-pleuritis, atelectasis of the superior segment of the lower lobe
      (S6), obstructive pneumonia in the middle and lower lobes due to stenosis of the
      intermediate bronchus, pneumonia of the upper lobe, and superior accessory
      fissure with atelectasis of the upper lobe.

PMID- 15726895
TI  - [Stereotactic vacuum-assisted breast biopsy (Mammotome biopsy) for non-palpable
      microcalcification on mammography].
AB  - PURPOSE: The purpose of this study was to assess the benefits of stereotactic
      vacuum-assisted breast biopsy in patients with non-palpable microcalcification
      detected on mammography. METHODS: Between October 2001 and November 2003,
      stereotactic Mammotome biopsies were performed for 150 microcalcified lesions on
      mammography using the prone-type stereotactic vacuum-assisted breast biopsy
      system (Mammotest and Mammovision, Fischer, Denver, USA) . The mammography
      findings were classified according to the guidelines of The Japan Radiological
      Society/The Japan Association of Radiological Technologists. Ninety-eight cases
      were category 3, 38 were category 4, and 14 were category 5. RESULTS: All cases
      were determined to be cases of microcalcification by specimen radiography or
      histology. Complications were negligible. One hundred twenty of the cases were
      mastopathy, and 30 of them were breast cancer (14 were ductal carcinoma in situ,
      7 were ductal carcinoma in situ with microinvasion, and 9 were invasive ductal
      carcinoma). Twenty-seven breast cancers were diagnosed as category 4 or 5 (51.9%)
      on mammography. The operative stages of 27 cases were as follows: 7 were stage 0,
      17 were stage 1, and 3 were stage 2A. Twenty-four of 27 (88.9%) were early breast
      cancers. CONCLUSION: Mammotome biopsy is a safe and useful modality for the
      histological diagnosis of non-palpable microcalcifications.

PMID- 15726896
TI  - [Effect of saline flush using dual injector on abdominal dynamic contrast
      enhanced computed tomography].
AB  - PURPOSE: To evaluate the efficacy of the saline flush technique for abdominal
      multidetector-row computed tomography (CT). METHODS: As a clinical study, 147
      patients with chronic hepatic disease were divided into two groups: group A,
      given 100 cc of contrast material flushed with 50 cc of saline; and group B,
      given 100 cc of contrast material only. The difference in attenuation values
      between groups A and B, and cirrhotic liver and non-cirrhotic liver were
      evaluated. As an in-vitro experimental study, time vs. peak pressure curve was
      obtained changing injection devices. RESULTS: Group B showed a greater contrast
      enhancement effect in the early arterial equilibrium phase of the aorta and late
      arterial phase of the liver. In cirrhotic liver, the aorta showed greater
      contrast enhancement in the early arterial phase in group A. Attenuation values
      of hypervascular hepatic nodules showed no statistically significant difference
      between groups A and B. Time to reach peak pressure was prolonged when using
      saline flush devices in vitro. Flow of contrast material from the contrast
      material cylinder to the saline cylinder was also discovered. CONCLUSION: Saline
      flush causes peak arterial contrast to be strong for a short duration. Abdominal
      organ attenuation values are not necessarily increased in the saline flush
      method. It is important to know that contrast enhancement is dependent on the
      injection device.

PMID- 15726897
TI  - [Usefulness of diffusion-weighted MRI in differentiating benign from malignant
      musculoskeletal tumors].
AB  - PURPOSE: To evaluate the usefulness of diffusion-weighted MRI in distinguishing
      different components and in differentiating benign from malignant musculoskeletal
      tumors. MATERIALS AND METHODS: Fifty-seven patients with musculoskeletal tumors
      underwent MR at our institution from October 1999 to April 2002. We evaluated 57
      tumors (9 bone tumors and 48 soft tissue tumors). All tumors were classified into
      8 groups (myxomatous, fibrous, cystic, cartilaginous, fatty components,
      hematomas, other benign tumors, and other malignant tumors). MR examinations were
      performed with a 1.5-Tesla system. Diffusion-weighted single-shot EPI images were
      obtained in all patients. Apparent diffusion coefficients (ADCs) were calculated
      by using b factors of 0 and 1,000 sec/mm2. RESULTS: ADC values of myxomatous,
      cystic, and cartilaginous components were significantly higher than those of
      other tumors. In cartilaginous tumors, malignant tumor ADC values (2.33 +/- 0.44)
      were higher than those of benign tumors (2.13 +/- 0.13). However, there was no
      significant difference between benign and malignant tumors. Except for high
      intensity components on T1-weighted imaging and low or homogeneously very high
      intensity components on T2-weighted imaging, there was a significant difference
      in ADC between malignant (1.35 +/- 0.40) and benign (1.97 +/- 0.50) tumors.
      CONCLUSION: Within the limited number of cases, there was a significant
      difference in ADC between malignant and benign tumors.

PMID- 15726898
TI  - [Histological changes in the rabbit kidney induced by transarterial injection of
      a hypertonic sodium chloride solution].
AB  - PURPOSE: To evaluate histological changes in normal renal tissue induced by the
      injection of a hypertonic liquid. MATERIALS AND METHODS: Transarterial injection
      was performed in 17 healthy rabbits at various rates of infusion and amounts of
      isotonic and hypertonic (7%) sodium chloride solutions. In group 1, 10 cc of
      isotonic sodium chloride solution was injected. In groups 2 and 3, 1-10 cc of
      hypertonic solution was injected at rates of 1.0 cc/sec and 0.05 cc/sec,
      respectively. After 20 minutes of hemostasis, renal weight measurements and
      histological examinations were performed. In three rabbits that received 10 cc of
      7% sodium chloride, lung samples were also obtained, and histological changes
      were reviewed. RESULTS: There was no tissue injury in group 1, and in groups 2
      and 3 the histological changes for infusions of 4-10 cc were greater than those
      of 1-3 cc. There was no vascular endothelial cell damage in any case. None of the
      histological changes were dose dependent, and the lungs showed no clear
      histological alterations. CONCLUSION: Higher doses of a hypertonic sodium
      chloride solution cause irreversible histological changes in the rabbit kidney.

PMID- 15726899
TI  - [Teleradiology using uncompressed DICOM format via exclusive fiber-optic system].
AB  - We developed a system for teleradiology using exclusive fiber optics for
      transferring images formatted in uncompressed DICOM. This system was built up
      with commercially available machines and software provided from various
      companies. We are now operating the system with five remote hospitals and have
      had one year of experience. The current system took advantage of the security and
      transfer efficiency of exclusive fiber optics. Uncompressed DICOM images were
      useful for the identification of cases and user-friendly for viewing. The reading
      room is located in our university hospital, and the location is convenient for
      consultation and discussion of cases.

PMID- 15726900
TI  - [History of radiation therapy].

PMID- 15726901
TI  - Changes in gene expression in the lungs of Mg-deficient mice are related to an
      inflammatory process.
AB  - It has been well documented that experimental hypomagnesemia in rodents evokes,
      as an early consequence, an inflammatory response. This also leads to the
      activation of cells producing reactive species of oxygen and, as a result, to the
      oxidative damage of tissues. Several studies have shown that lungs might be a
      specific target of Mg deficiency. Here, we report that 3 weeks of Mg deficiency
      in mice resulted in inflammatory processes in the lungs, including interstitial
      and perivascular pneumonia, manifested by the infiltration of leukocytes,
      plasmocytes and histiocytes, as well as the phenomenon of disseminated
      intravascular coagulation (DIC). These phenomena were accompanied by changes in
      gene expression assessed by cDNA array. In this study we identified 26 genes
      significantly changed by Mg deficiency, mostly involved in the anti-oxidative
      response, regulation of cell cycle and growth, apoptosis as well as cell-cell and
      cell-matrix interactions. We conclude that these changes are related to the
      phenomena of inflammatory and oxidative processes and consecutive remodeling
      occurring in the tissues as a result of Mg deficiency. This may have implications
      for at least several lung pathologies, including allergies, asthma, SIDS (Sudden
      Infant Death Syndrome) or facilitate formation of lung metastases.

PMID- 15726902
TI  - Early-onset increased calcium and decreased magnesium concentrations and an
      increased calcium/magnesium ratio in SHR versus WKY.
AB  - Alterations in the metabolism of calcium and magnesium have been implicated in
      the pathogenesis of primary hypertension. Calcium influx across the external
      cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role
      in the control of cellular excitation contraction and impulse propagation.
      Intracellular calcium and magnesium concentrations are controlled by reversible
      binding to specific calcium binding proteins. The calcium and magnesium flux
      across the external membrane is regulated by a calcium pump (calcium-magnesium
      ATPase), calcium channels and binding to the membrane. In cell membranes and in
      lymphocytes of essential hypertensives, our group showed increased calcium and
      decreased magnesium and an increased calcium/magnesium ratio in hypertensive
      cells. In this context, in aortic smooth muscle cells from 13 spontaneously
      hypertensive rats (SHR) of the Munster strain (systolic blood pressure 188.4+/
      9.8 mmHg) and 13 normotensive rats (NT, systolic blood pressure 118.5+/-7.2 mmHg)
      aged 9 months, the intracellular calcium and magnesium contents were measured
      under nearly in vivo conditions by electron-probe microanalysis. Measurements
      were performed in aortic cryosections 3 microm thick. The calcium content was
      124.7+/-4.5* mmol/kg dry weight in SHR versus 110.3+/-4.1 mmol/kg dry weight in
      NT (Means+/-SD, p < 0.01), the magnesium content was 35.5+/-3.9* in SHR versus
      50.1+/-4.9 mmol/kg dry weight in NT /p < 0.01). The calcium/magnesium ratio was
      significantly increased in SHR versus NT (3.56+/-0.39* versus 2.23+/-0.27, p <
      0.01). In hypertensive one month old animals the increase in the
      calcium/magnesium ratio was not as pronounced as in 9 month old animals. The
      calcium/magnesium ratio was measured 3.3+/-0.42 in SHR (n = 8) as compared to
      2.51+/-0.39 in normotensive animals (n = 8, p < 0.01). Aortic smooth muscle cells
      from SHR are characterized by markedly elevated intracellular calcium and
      decreased intracellular magnesium contents compared with normotensive cells. The
      increased calcium/magnesium ratio in hypertensive cells may be a pathogenetic
      factor for the development of arteriosclerosis and hypertension.

PMID- 15726903
TI  - Effects of diabetes and insulin resistance in pregnant rats on ex vivo vascular
      reaction to magnesium.
AB  - The purpose of this study was to investigate the effects of diabetes and insulin
      resistance during pregnancy on the ex vivo vascular reaction to magnesium. Female
      Sprague-Dawley rats were made diabetic by intravenous injection of alloxan, or
      insulin resistant by fructose feeding. The rats were allowed to mate and
      sacrificed on Day 19 of pregnancy. Aortic rings were isolated and mounted in
      organ baths for measurement of isometric tension. The rings were contracted with
      10(-7) M phenylephrine and cumulative concentration-response curves for magnesium
      (1-12 mM) were determined in the presence and absence of 10(-4) M Nomega-nitro-L
      arginine methyl ester (L-NAME) or 10(-5) M indomethacin. The relaxation response
      to magnesium was significantly decreased in pregnant rats compared with non
      pregnant rats. Pregnant rats with diabetes or insulin resistance had greater
      impairment in the relaxation responses to magnesium compared with normal pregnant
      rats. The effects of diabetes and insulin resistance on magnesium-induced
      relaxation in pregnant rats were not altered in the presence of L-NAME and
      indomethacin. The results suggest that diabetes and insulin resistance aggravate
      the alteration in magnesium-induced vascular relaxation observed in pregnancy,
      and this may be due in part to impairment to mechanisms other than the nitric
      oxide-cyclic guanosine monophosphate and cyclooxygenase pathways.

PMID- 15726904
TI  - Comparative study of the efficacy of potassium magnesium L-, D- and DL-aspartate
      stereoisomers in overcoming digoxin- and furosemide-induced potassium and
      magnesium depletions.
AB  - Potassium and magnesium aspartate (K,Mg aspartate) is used in treating and
      preventing cardiac disruptions caused by electrolytic disturbances, primarily low
      potassium (K) and magnesium (Mg) levels (e.g. in the treatment with cardiac
      glycosides and diuretic drugs). Widely used, K,Mg aspartate is synthesized from
      aspartic acid representing a racemic mix of L- and D-stereoisomers. Differences
      in metabolism and utilisation of D- and L-amino acids probably have an effect on
      the pharmacological properties of K,Mg L- and D-aspartates, and what is more,
      pharmacological doses of magnesium and potassium salts may induce toxicity, which
      differs according to the nature of the anions. Therefore, the purpose of the
      present work was to study the effect of intravenously administered K,Mg L
      aspartate in comparison with its D- and DL-stereoisomers on K and Mg restoration
      rates in plasma, erythrocytes and myocardium and to evaluate the urine excretion
      rate of amine nitrogen and Mg in digoxin and furosemide treated rats. To induce
      Mg depletion, male rats, weighing 180-200 g, were given furosemide and digoxin at
      doses of 30 mg/kg (i.p.) and 0.25 mg/kg (i.p.) daily for 14 days. After 14 days
      K,Mg L-, D- and DL-aspartates were administered with simultaneous furosemide and
      digoxin treating at dose of 100 mg/kg (i.v.), which corresponds to 46.95 mg of Mg
      aspartate (i.e. Mg = 3.96 mg) and 53.05 mg of K aspartate (i.e. K = 12.12 mg) per
      kg bodyweight. Erythrocyte, plasma and urine Mg levels were measured by
      colorimetric assay using the method based on the staining reaction of Mg and
      thiazole yellow. Myocardium Mg and K content and erythrocyte K levels were
      determined by flame atomic absorption spectroscopy. The level of amine nitrogen
      was measured by colorimetric assay using the method based on the staining
      reaction with ninhydrin. It was shown that K,Mg L-aspartate administration leads
      to higher compensation of K and Mg deficiency in rats with furosemide and digoxin
      induced K and Mg depletion, as compared with D- and DL-stereoisomers. According
      to the K and Mg deficiency correction rate, K,Mg aspartates may be ranged in the
      following order: K, Mg L-aspartate > K,Mg DL-aspartate > K,Mg D-aspartate. It was
      shown that after administration of K,Mg L-aspartate, daily urine excretion of
      amine nitrogen and Mg is less than after D- and DL-stereoisomer administration.
      According to the quantity of excreted amine nitrogen and Mg in urine, K,Mg
      aspartates may be ranged in the following order: K,Mg D-aspartate = K, Mg DL
      aspartate > K,Mg L-aspartate. So, K,Mg L-aspartate is more beneficial in the
      treatment of several forms of primary Mg and K deficiency than K,Mg DL-aspartate
      and K, Mg D-aspartate.

PMID- 15726905
TI  - Studies on the development of an insulin resistant rat model by chronic feeding
      of low magnesium high sucrose diet.
AB  - Magnesium deficiency and excess sucrose in the diet have been shown to play an
      important role in the development of insulin resistance. In the present study we
      have looked at the combined effect of a low magnesium high sucrose diet on basal
      glucose and insulin levels, erythrocyte insulin receptors and lipid profile in
      rats. For this purpose rats were divided into four groups and fed control, low
      magnesium, high sucrose and low magnesium high sucrose diets respectively for
      three months. The biochemical analysis showed a significant increase in blood
      glucose and triglyceride levels after one, two and three months of feeding in
      both the high sucrose and the low magnesium high sucrose groups, while rats fed a
      low magnesium diet showed a significant increase in blood glucose and
      triglyceride levels only after the second month. Insulin levels increased
      significantly in low magnesium, high sucrose and low magnesium high sucrose
      groups by the end of the study period. Compared to control rats, the binding of
      insulin to the erythrocyte insulin receptors was reduced significantly in the
      high sucrose and the low magnesium high sucrose groups. Cholesterol levels were
      found to increase significantly in the high sucrose group at the end of one month
      and three months of feeding. HDL-cholesterol decreased significantly in the low
      magnesium high sucrose group by the end of the study. Serum and RBC magnesium
      levels demonstrated a significant decrease in the low magnesium and the low
      magnesium high sucrose groups. The post heparin plasma lipoprotein lipase
      activity was decreased significantly in low magnesium, high sucrose and low
      magnesium high sucrose groups compared to control rats. These findings suggest
      that feeding a diet low in magnesium and high in sucrose causes insulin
      resistance in rats.

PMID- 15726906
TI  - Potentials of magnesium treatment in subarachnoid haemorrhage.
AB  - Subarachnoid hemorrhage from a ruptured aneurysm is a subset of stroke. The young
      age (median 55 years) and poor outcome (50% of patients die; 30% of survivors
      remain dependent) explain why in the population the loss of productive life years
      from aneurysmal subarachnoid hemorrhage (SAH) is as large as that from brain
      infarcts, the most common type of stroke. Ischemia plays an important role in the
      pathophysiological process after SAH. A period of global cerebral ischemia
      firstly occurs in the acute phase, immediately after rupture of the aneurysm, due
      to acute vasoconstriction and elevated intracranial pressure, which leads to a
      drop in perfusion pressure. This is quite distinct from the secondly, delayed
      cerebral ischemia (DCI), which is focal or multi-focal. DCI usually occurs
      between 4 and 10 days after the initial bleeding, has a gradual onset and is
      multi-focal, and is an important cause of death and dependency after SAH. The
      interval between the bleeding and the onset of ischemia provides an opportunity
      for preventive treatment. Magnesium is readily available, inexpensive and has a
      well-established clinical profile in obstetrical and cardiovascular practice. It
      is beneficial in the treatment of eclampsia, a disease with a pathophysiology
      comparable to DCI after subarachnoid hemorrhage. Neuroprotective mechanisms of
      magnesium include inhibition of the release of excitatory amino-acids and
      blockade of the NMDA-glutamate receptor. Magnesium is also a non-competitive
      antagonist of voltage dependent calcium channels, has cerebrovascular dilatory
      activity and is an important co-factor of cellular ATPases, including the Na/K
      ATPase. Magnesium can reverse delayed cerebral vasospasm and reduces the extent
      of acute ischemic cerebral lesions after experimental subarachnoid hemorrhage in
      rats. In this article we discuss the neuroprotective potency of magnesium in SAH
      by describing the pathophysiology of ischaemia after SAH and the many ways
      magnesium may interfere with this.

PMID- 15726907
TI  - Importance of magnesium depletion with hypofunction of the biological clock in
      the pathophysiology of headhaches with photophobia, sudden infant death and some
      clinical forms of multiple sclerosis.
AB  - Mg depletion is a type of Mg deficit due to a dysregulation of the Mg status. It
      cannot be corrected through nutritional supplementation only, but requires the
      most specific correction of the dysregulating mechanism. Among those, Biological
      Clock (BC) dysrhythmias are to be considered. The aim of this study is to analyze
      the clinical forms of Mg depletion with hypofunction of the Biological Clock
      (hBC). hBC may be due to either Primary disorders of BC [Suprachiasmatic Nuclei
      (SCN) and pineal gland (PG)] or Secondary with homeostatic response [reactive
      Photophobia (Pphi] to light neurostimulating effects [Nervous Hyper Excitability
      (NHE)]. The symptomatology is mainly diurnal and observed during fair weather
      (Spring,Summer). The elective marker of hBC is represented by a decrease in
      melatonin and in its metabolites in various fluids. The clinical forms of NHE due
      to Mg depletion with hBC are central and peripheral. The central forms associate
      anxiety, headaches and dyssomnia. The peripheral manifestations are
      neuromuscular: photosensitive epilepsia mainly. Three chronopathological forms of
      Mg depletion with hBC have been highlighted: 1. Headaches with Pphi: mainly
      migraine; 2. Sudden Infant Death Syndrome (SIDS); 3. Multiple Sclerosis (MS).-
      Headaches with Pphi, migraine particularly. These cephalalgias are diurnal with
      Pphi and are aggravated during the fair seasons (particularly during midnight sun
      summer). Migraine is their typical form with its dishabituation to visual stimuli
      and its occipital cortex hyperexcitability. Comorbidity with anxiety is frequent.
      In 2/3 of the cases, it appears first.- SIDS might be linked to an impaired
      maturation of both photoendocrine system and brown adipose tissue. MS may be
      associated with primary disorders of BC Clinical forms of Mg depletion with hBC
      in MS present diurnal exacerbations and relapses during fair seasons. They have
      been underestimated because they disagree with the dogma of the << latitude
      gradient >>, presently questioned. Comorbidities with anxiety and migraine are
      frequent.hBC may be treated by using darkness therapy with a balanced Mg status.
      Absolute light deprivation should only be used only in acute indications and is
      time-limited. Partial substitutive therapy and chromatotherapy have not been
      validated yet and are still uncertain.

PMID- 15726908
TI  - State of the art of new data on the role of magnesium in brain injury: clinical
      interest of measurements of total and ionized magnesium.
AB  - Despite many research studies on traumatic brain injury, few markers have been
      applicable to diagnose trauma at tissue concentration. Today, the importance of
      the magnesium ion in posttraumatic homeostasis of brain is a well-known reality.
      Magnesium concentration affects a number of secondary injury factors including
      neurotransmitter release, ion changes, oxidative stress, protein synthesis, and
      energy metabolism. There are many experimental and clinical studies relating to
      magnesium status in brain injury. It was considered by some authors that only the
      total form of magnesium should be measured in brain injury. However, recent
      studies point out that measurement of the ionized form also aids in the
      intervention of patients with brain trauma. This review aims to explain the role
      of magnesium in brain injury and to assess the real status of magnesium through
      pertinent tests.

PMID- 15726909
TI  - New data on the bioavailability of bread magnesium.
AB  - Whole cereal products are the main source of magnesium in human nutrition. Even
      if wholemeal bread is an important source of Mg, it also contains considerable
      amounts of phytic acid (PA), a natural chelator that lowers the absorption of
      trace elements such as Fe or Zn as well as Ca or Mg in cereal products.
      Significant Mg bioavailability improvement in bread could be supplied by the
      choice of raw materials and the baking processes of cereals. Improvement in the
      Mg content of wheat grain was proved possible by traditional plant selection.
      Bread making using sourdough improves the nutritional properties of bread by
      reducing the amounts of phytic acid and phytate breakdown, which is mainly
      explained by the acidity level in the sourdough process that promotes greater
      efficiency in the wheat phytase activity. A slight acidification due to sourdough
      effectively reduces the phytate content and improves Mg bioavaibility.

PMID- 15726910
TI  - Management of anovulatory infertility associated with polycystic ovary syndrome:
      tamoxifen citrate an effective alternative compound to clomiphene citrate.
AB  - Clomiphene citrate (CC) is widely used as first-line treatment for ovulation
      induction in anovulatory women with polycystic ovary syndrome (PCOS). Tamoxifen
      citrate (TMX), another non-steroidal selective estrogen receptor modulator, may
      also be effective on the resumption of ovulation in these women. The aim of this
      controlled observational study was to compare the efficacy and safety of
      ovulation induction with TMX versus CC in anovulatory infertile women with PCOS.
      A total of 102 consecutive women (mean age+/-SD: 31+/-3.6 years; range: 26-38)
      with PCOS were studied. Following a spontaneous or progesterone-induced
      withdrawal bleed, women received either 50 mg daily of CC (days 2-6) or 20 mg
      daily of TMX (days 2-5). In case ovulation failed to occur, the dose was
      sequentially increased to 100 mg daily of CC and 40 mg daily of TMX,
      respectively. Serum progesterone levels were measured on cycle day 21 to monitor
      the ovulation pattern. The overall ovulation rate was significantly higher in
      women who received TMX compared with those who received CC (61/98, 62.2% vs.
      60/127, 47.2%, p=0.03). Although not statistically significant, the pregnancy
      rate per ovulatory cycle was higher in the TMX group compared to the CC group
      (14/61, 22.9% vs. 11/60, 18.3%, respectively). All pregnancies were single and
      there were no side-effects in either group of treatment. Collectively, these data
      demonstrate that TMX is a safe and effective agent, and a suitable alternative to
      CC for anovulatory infertility in women with PCOS.

PMID- 15726911
TI  - Involvement of a nitric oxide-cyclic guanosine monophosphate pathway in control
      of fallopian tube contractility.
AB  - Fallopian tube smooth muscle contractions are physiologically related to
      transport of the ovum within the oviduct. Nitric oxide (NO) has proved to be a
      mediator of tubal contractility. The main pathway by which NO exerts its relaxing
      effect on tubal contractions has not been fully elucidated. NO-mediated effects
      may be cyclic guanosine monophosphate (cGMP)-dependent or cGMP-independent. The
      objective of the present study was to investigate whether a NO-cGMP pathway is
      present in the Fallopian tube and, if present, to examine whether this pathway is
      involved in tubal contractility. Tubal smooth muscle strips were mounted in organ
      baths for measurement of tissue cGMP and for isometric recording of contractile
      activity. Following administration of the NO donor spermine NONOate a more than
      three-fold increase in tissue levels of cGMP was measured. Pretreatment with
      inhibitors of cGMP production prior to administration of spermine NONOate
      resulted in similar levels of cGMP as found in strips exposed to only plain
      buffer solution. Administration of spermine NONOate to muscle baths resulted in a
      significant inhibition of contractile activity, while pretreatment with
      inhibitors of cGMP production almost eliminated the relaxing effect of the NO
      donor. This study showed that a NO-cGMP pathway is present in the Fallopian tube
      and that the pathway is involved in Fallopian tube contractility.

PMID- 15726912
TI  - Inclusion of standard and low-dose gonadotropin releasing hormone-analog (short
      protocol) in controlled ovarian hyperstimulation regimens in normogonadotropic
      patients aged 40-48 years who are undergoing in vitro fertilization.
AB  - We aimed to compare the efficiency of three controlled ovarian hyperstimulation
      protocols in achieving superovulation in normogonadotropic patients aged 40 years
      or more, who were undergoing in vitro fertilization (IVF) treatment. This was a
      prospective randomized clinical study, carried out in the Infertility and IVF
      Unit of an academic tertiary hospital. A total of 219 normogonadotropic patients
      (serum follicular stimulating hormone level < 15 mIU/ml) aged 40-48 years, with
      regular menstrual cycles, were randomly allocated to one of three short
      follicular protocols: menotropins only (group A), menotropins plus a mini-dose of
      gonadotropin releasing hormone (GnRH)-analog (600 microg/ day) (group B), or
      menotropins plus a standard dose (900 microg/day) of a GnRH-analog (group C).
      Those cycles that reached the stage of oocyte retrieval (67, 70 and 71 cycles,
      respectively) were analyzed. The mean daily dose of menotropins needed for
      ovarian stimulation was higher when GnRH-analog was used (groups B and C) (p <
      0.02; ANOVA), although there was no significant difference in the time of human
      chorionic gonadotropin injection (average: cycle day 11). Peak estradiol levels
      (p < 0.02), number of oocytes retrieved (3.9, 5.4 and 5.5 oocytes/cycle,
      respectively, p < 0.02) and number of embryos transferred (1.6, 1.8 and 2.1
      embryos/cycle, respectively, p < 0.05) were higher when GnRH-analog was included
      in the controlled ovarian hyperstimulation protocol. The IVF treatment resulted
      in 19 pregnancies (9.1% implantation rate), with a similar distribution among all
      three groups (11.9%, 8.6% and 7.0%). However, a higher miscarriage rate was noted
      in the menotropins-only group (67.5% vs. 33.3% and 40.0% of pregnancies). No
      differences were observed in any of the aforementioned variables between the mini
      dose and standard dose GnRH-analog groups (groups B and C). In conclusion,
      controlled ovarian hyperstimulation before IVF treatment in normogonadotropic
      patients aged 40 years or more is more effective when a GnRH-analog (short
      protocol) is included in the treatment regimen. In this selected group of
      patients, reducing the daily dose of GnRH-analog does not improve the treatment
      results.

PMID- 15726913
TI  - Does previous surgery influence the asymmetric distribution of endometriotic
      lesions?
AB  - Our objective was to investigate the role of previous abdominal-pelvic surgery in
      the asymmetric distribution of pelvic endometriosic lesions. This was a
      retrospective study carried out at the Clinic of Obstetrics and Gynecology,
      University of Ancona, Italy, and included 238 patients with histological
      confirmation of endometriosis. The interventions were surgical treatment, at
      laparoscopy or laparotomy, for pelvic pain and endometriosis. The main outcome
      measure(s) were endometriotic lesions and adhesions in the pelvis found during
      surgery and the dinical records of the patients. We found unilateral lesions in
      149 patients (62.6%): the right side of the pelvis affected in 55 patients
      (36.9%) and the left side in 94 patients (63.1%) (p < 0.01). In the group of
      patients who had undergone previous abdominal surgery, we found lesions on the
      right side in 26 cases (32.5%), and on the left in 54 cases (67.5%) (p < 0.01).
      We found that the patients who had undergone previous abdominal surgery had
      significantly more adhesions than those with no previous surgery (80/116 vs.
      73/122, p = 0. 002). As a new finding, we have demonstrated that the left side of
      asymmetric distribution of intrapelvic macroscopic lesions is preserved and more
      evident in patients with previous abdominal surgery, including previous
      appendectomy. These data seem to be in agreement with our previous supposition of
      a possible interaction between previous abdominal surgery and the mechanisms of
      endometriosis development.

PMID- 15726914
TI  - Placental growth by the estrogen-dependent angiogenic factors, vascular
      endothelial growth factor and basic fibroblast growth factor, throughout
      gestation.
AB  - Angiogenesis is essential for the development and growth of the human placenta
      throughout gestation, under the influence of enriched estrogen. This prompted us
      to study the clinical implications of estrogen-dependent angiogenic factors
      derived from the human placenta. Fifty-eight women ranging from 6 to 41 weeks'
      gestational age (25 in the first trimester, 12 in the second trimester and 21 in
      the third trimester) underwent abortion and delivery. The levels of angiogenic
      factors in the placenta were determined by enzyme immunoassay, and the mRNA and
      protein of vascular endothelial growth factor (VEGF) variants were analyzed by
      reverse transcriptase-polymerase chain reaction and Western blotting,
      respectively. The levels of VEGF, especially VEGF165, and bFGF correlated with
      placental weights throughout gestation. Estrogen-dependent VEGF, especially
      VEGF165, and bFGF might work on growth via angiogenesis in the human placenta
      throughout all trimesters of gestation.

PMID- 15726915
TI  - Changes in serum levels of leptin, cytokines and lipoprotein in pre-eclamptic and
      normotensive pregnant women.
AB  - The aim of this study was to investigate the changes in serum levels of leptin,
      cytokines and lipoproteins in women with pre-eclampsia and to evaluate their
      clinical significance in the pathogenesis of pre-eclampsia. We performed a
      prospective study involving 45 women with pre-eclampsia in the third trimester of
      pregnancy and 30 normotensive women in the third trimester of pregnancy. Serum
      level of leptin was measured by enzyme immunoassay using a Cayman chemical kit.
      Serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta,
      soluble IL-2 receptor (slL-2R), IL-6 and IL-8 were measured by using a non
      radioimmunoassay chemiluminescent method. Serum lipid concentrations were
      measured by an Abbott Aeroset (USA) autoanalyzer. Serum levels of apolipoprotein
      (Apo)A-I and ApoB were evaluated by nephelometrics assays. Differences between
      groups were evaluated with Student's unpaired t test and, when a variable was not
      normally distributed, the Mann-Whitney U test was used. The relationship between
      the variable was explored by the Pearson correlation test. Serum levels of
      leptin, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 in the pre-eclamptic women
      were significantly higher than in normotensive women (p < 0.001). In the pre
      eclamptic women serum levels of triglycerides, total cholesterol and low-density
      lipoprotein (LDL)-cholesterol were significantly increased (p < 0.001), while
      high-density lipoprotein (HDL)-cholesterol and Apo-A were significantly decreased
      compared to levels in normotensive pregnant women (p < 0.001). No significant
      differences were noted between the groups in Apo-B (p > 0.05). Serum levels of
      TNF-alpha were significantly correlated with the serum levels of IL-6, IL-8,
      triglycerides, sIL-2R, Apo-A and hematocrit in pre-eclamptic women (r = 0.418, p
      < 0.05; r= 0.389, p < 0.01; r=0.312, p < 0.05; r= -0.318, p < 0.05; r= -0.340, p
      < 0.05 and r=0.41, p < 0.01, respectively). A negative correlation was seen
      between serum level of leptin and both IL-1beta and Apo-A in pre-eclamptic women
      (r=-0.44, p < 0.05; r=-0.39, p < 0.05, respectively). Serum levels of IL-6 were
      also significantly correlated with the serum levels of HDL-cholesterol, LDL
      cholesterol and body mass index (BMI) in pre-eclamptic women (r=0.40, p < 0.01;
      r=-0.568, p < 0.01; r= -0.30, p < 0.05, respectively). In addition, serum level
      of IL-8 were significantly correlated with the serum levels of HDL-cholesterol,
      total cholesterol and BMI in pre-eclamptic women (r= 0.368, p < 0.05; r=0.513, p
      < 0.01 and r= -0.41, p < 0.01, respectively). We found that the pre-eclampsia
      associated with increases in serum levels of leptin, TNF-alpha, cytokines,
      triglycerides, total cholesterol and LDL-cholesterol was associated with a
      significant reduction in serum levels of HDL-cholesterol and Apo-A. These
      association may be due to the abnormal lipid metabolism and immune activation
      involved in the pathogenesis of this disease.

PMID- 15726916
TI  - Transdermal hormone replacement therapy and Doppler findings in normal and
      overweight postmenopausal patients.
AB  - The aim of this study was to evaluate the effects of transdermal hormone
      replacement therapy on some biological cardiovascular risk factors, specifically
      the thromboxane B2 levels, plasma viscosity and the lipid profile. Furthermore,
      we investigated the Doppler flow modifications at the level of the uterine
      artery, the internal carotid, the ophthalmic and the bladder wall arteries, and
      we finally evaluated whether there were significant differences in the examined
      parameters between normal and overweight postmenopausal women. Forty-five
      postmenopausal women (mean age+/-standard deviation, 53.5+/-3.8 years)
      participated in the study and were divided into two groups (27 with a body mass
      index of < 25 kg/m2 and 18 with a body mass index of > 25 kg/m2). Patients were
      treated with a continous estradiol transdermal supplement and a 12-day course of
      medroxyprogesterone acetate every 2 months, and were studied at baseline and
      after 6 months (in the estrogen-only phase of the second cycle). Our results
      showed a beneficial effect of hormone substitution on plasma viscosity,
      thromboxane B2 levels and lipid profile after 6 months of therapy and significant
      improvements of Doppler flow parameters in the examined vessels. Furthermore, we
      observed a lower impact of the treatment in overweight women. In conclusion,
      obesity represents an additional cardiovascular risk condition and it can only
      partially be modified by the administration of hormone replacement therapy.

PMID- 15726917
TI  - Effects of estradiol on myocardial global performance index in hypertensive
      postmenopausal women.
AB  - The objective of this study was to assess the acute and chronic effects of
      estradiol on the myocardial performance index (MPI) in hypertensive
      postmenopausal women. There are conflicting reports on the effects of estrogen on
      left ventricular function in postmenopausal women, and we are unaware of any
      study on the myocardial performance index in the postmenopausal state. We
      undertook a prospective, randomized, double-blind, placebo-controlled study in 34
      women, distributed into an estradiol group or a placebo group. After 90 min and
      at 12 weeks of administration of 1 mg of oral estradiol we evaluated, by Doppler
      echocardiography, its effects on the MPI. The estradiol group showed no
      alteration in the MPI after 90 min of the administration of estradiol. On the
      other hand, after 12 weeks of treatment we observed a statistically significant
      decrease of isovolumic relaxation time, from 127+/-23 ms to 106+/-16 ms (p <
      0.001 and of the MPI from 0.63+/-0.13 to 0.48+/-0.09 (p < 0.01) and an increase
      in ejection time, from 297+/-32 ms to 330+/-31 ms (p < 0.01). In conclusion,
      estrogen replacement therapy over a period of 12 weeks showed a significant
      improvement in the MPI in hypertensive postmenopausal women, whereas the acute
      administration did not have any effect.

PMID- 15726918
TI  - Basic tenets for water management.

PMID- 15726919
TI  - Comment on the "Climate change: why should water professionals care?" editorial
      by Marios Sophocleous (Ground Water 42, no. 5: 637).

PMID- 15726920
TI  - Remediation of DNAPL source zones with granular iron: laboratory and field tests.
AB  - Degradation of dissolved chlorinated solvents using granular iron is an
      established in situ technology. This paper reports on investigations into mixing
      iron and bentonite with contaminated soil for in situ containment and degradation
      of dense nonaqueous phase liquid source zones. In the laboratory, hypovials
      containing soil, water, bentonite, iron, and free-phase trichloroethene (TCE)
      were assembled. Periodic measurement of TCE, chloride, and degradation products
      showed progressive degradation of TCE to nondetectable levels. Subsequently, a
      demonstration was conducted at Canadian Forces Base Borden near Alliston,
      Ontario, Canada, where, in 1991, a portion of the surficial aquifer was isolated
      and free-phase tetrachloroethene (PCE) was introduced. Using a drill rig equipped
      with large-diameter mixing blades, three mixed zones were prepared containing 0%,
      5%, and 10% granular iron by volume. The bentonite was added to serve as a
      lubricant to facilitate injection of the iron and to isolate the contaminated
      zone. Analysis of core samples showed reasonably uniform distributions of iron
      through the mixed zones. Monitoring over a 13-month period following installation
      showed, relative to the control, a decline in PCE concentrations to virtually
      nondetectable values. Reaction rates in the laboratory tests were similar to
      those reported in the literature, while the rate in the field test was
      substantially lower. The lower rate may be a consequence of mass transfer
      limitations under the static conditions of the field test. Results indicate that
      mixing iron and bentonite into source zones may be an effective means of source
      zone remediation, with the particular advantage of being relatively immune to
      effects of geologic heterogeneity.

PMID- 15726921
TI  - Direct-push hydrostratigraphic profiling: coupling electrical logging and slug
      tests.
AB  - Spatial variations in hydraulic conductivity (K) can significantly affect the
      transport of contaminants in ground water. Conventional field methods, however,
      rarely provide a description of these variations at the level of detail necessary
      for reliable transport predictions and effective remediation designs. A direct
      push (DP) method, hydrostratigraphic profiling, has been developed to
      characterize the spatial variability of both electrical conductivity (EC) and
      hydraulic conductivity in unconsolidated formations in a cost-effective manner.
      This method couples a dual-rod approach for performing slug tests in DP equipment
      with high-resolution EC logging. The method was evaluated at an extensively
      studied site in the Kansas River floodplain. A series of profiles was performed
      on a surface grid, resulting in a detailed depiction of the three-dimensional
      distribution of EC and K. Good agreement was found between K estimates obtained
      from this approach and those obtained using other methods. The results of the
      field evaluation indicate that DP hydrostratigraphic profiling is a promising
      method for obtaining detailed information about spatial variations in subsurface
      properties without the need for permanent wells.

PMID- 15726922
TI  - Matrix diffusion-derived plume attenuation in fractured bedrock.
AB  - Matrix diffusion can attenuate the rate of plume migration in fractured bedrock
      relative to the rate of ground water flow for both conservative and
      nonconservative solutes of interest. In a system of parallel, equally spaced
      constant aperture fractures subject to steady-state ground water flow and an
      infinite source width, the degree of plume attenuation increases with time and
      travel distance, eventually reaching an asymptotic level. The asymptotic degree
      of plume attenuation in the absence of degradation can be predicted by a plume
      attenuation factor, beta, which is readily estimated as R' (phi(m)/phi(f)), where
      R' is the retardation factor in the matrix, phi(m) is the matrix porosity, and
      phi(f) is the fracture porosity. This dual-porosity relationship can also be
      thought of as the ratio of primary to secondary porosity. Beta represents the
      rate of ground water flow in fractures relative to the rate of plume advance. For
      the conditions examined in this study, beta increases with greater matrix
      porosity, greater matrix fraction organic carbon, larger fracture spacing, and
      smaller fracture aperture. These concepts are illustrated using a case study
      where dense nonaqueous phase liquid in fractured sandstone produced a dissolved
      phase trichloroethylene (TCE) plume approximately 300 m in length. Transport
      parameters such as matrix porosity, fracture porosity, hydraulic gradient, and
      the matrix retardation factor were characterized at the site through field
      investigations. In the fractured sandstone bedrock examined in this study, the
      asymptotic plume attenuation factors (beta values) for conservative and
      nonconservative solutes (i.e., chloride and TCE) were predicted to be
      approximately 800 and 12,210, respectively. Quantitative analyses demonstrate
      that a porous media (single-porosity) solute transport model is not appropriate
      for simulating contaminant transport in fractured sandstone where matrix
      diffusion occurs. Rather, simulations need to be conducted with either a discrete
      fracture model that explicitly incorporates matrix diffusion, or a dual-continuum
      model that accounts for mass transfer between mobile and immobile zones.
      Simulations also demonstrate that back diffusion from the matrix to fractures
      will likely be the time-limiting factor in reaching ground water cleanup goals in
      some fractured bedrock environments.

PMID- 15726923
TI  - Upscaling of hydraulic conductivity and telescopic mesh refinement.
AB  - Performance assessments of repositories for the underground disposal of nuclear
      fuel and waste include models of ground water flow and transport in the host
      rocks. Estimates of hydraulic conductivity, K, based on field measurements may
      require adjustment (upscaling) for use in numerical models, but the choice of
      upscaling approach can be complicated by the use of nested modeling, large-scale
      fracture zones, and a high degree of heterogeneity. Four approaches to upscaling
      K are examined using a reference case based on exhaustive site data and an
      application of nested modeling to evaluate performance assessment of a waste
      repository. The upscaling approaches are evaluated for their effects on the flow
      balance between nested modeling domains and on simple measures of repository
      performance. Of the upscaling approaches examined in this study, the greatest
      consistency of boundary flows was achieved using the observed scale dependence
      for the rock domains, measured values from the large-scale interference test for
      the conductor domain, and a semivariogram regularization based on the Moye model
      for packer test interpretation. Making the assumption that large fracture zones
      are two-dimensional media results in the greatest changes to the median of travel
      time and improves the flow balance between the nested models. The uncertainty of
      upscaling methods apparently has a small impact on median performance measures,
      but a significant impact on the variances and earliest arrival times.

PMID- 15726924
TI  - Do conservative solutes migrate at average pore-water velocity?
AB  - According to common understanding, the advective velocity of a conservative
      solute equals the average linear pore-water velocity. Yet direct monitoring
      indicates that the two velocities may be different in heterogeneous media. For
      example, at the Camp Dodge, Iowa, site the advective velocity of discrete Cl-
      plumes was less than one tenth of the average pore-water velocity calculated from
      Darcy's law using the measured hydraulic gradient, effective porosity, and
      hydraulic conductivity (K) from large-scale three-dimensional (3D) techniques,
      e.g., pumping tests. Possibly, this difference reflects the influence of
      different pore systems, if the K relevant to transient solute flux is influenced
      more by lower-K heterogeneity than a steady or quasi-steady water flux. To test
      this idea, tracer tests were conducted under controlled laboratory conditions.
      Under one-dimensional flow conditions, the advective velocity of discrete
      conservative solutes equaled the average pore-water velocity determined from
      volumetric flow rates and Darcy's law. In a larger 3D flow system, however, the
      same solutes migrated at approximately 65% of the average pore-water velocity.
      These results, coupled with direct observation of dye tracers and their
      velocities as they migrated through both homogeneous and heterogeneous sections
      of the same model, demonstrate that heterogeneity can slow the advective velocity
      of discrete solute plumes relative to the average pore-water velocity within
      heterogeneous 3D flow sytems.

PMID- 15726925
TI  - Regional estimation of total recharge to ground water in Nebraska.
AB  - Naturally occurring long-term mean annual recharge to ground water in Nebraska
      was estimated by a novel water-balance approach. This approach uses geographic
      information systems (GIS) layers of land cover, elevation of land and ground
      water surfaces, base recharge, and the recharge potential in combination with
      monthly climatic data. Long-term mean recharge > 140 mm per year was estimated in
      eastern Nebraska, having the highest annual precipitation rates within the state,
      along the Elkhorn, Platte, Missouri, and Big Nemaha River valleys where ground
      water is very close to the surface. Similarly high recharge values were obtained
      for the Sand Hills sections of the North and Middle Loup, as well as Cedar River
      and Beaver Creek valleys due to high infiltration rates of the sandy soil in the
      area. The westernmost and southwesternmost parts of the state were estimated to
      typically receive < 30 mm of recharge a year.

PMID- 15726927
TI  - A closed form slug test theory for high permeability aquifers.
AB  - We incorporate a linear estimate of casing friction into the analytical slug test
      theory of Springer and Gelhar (1991) for high permeability aquifers. The modified
      theory elucidates the influence of inertia and casing friction on consistent,
      closed form equations for the free surface, pressure, and velocity fluctuations
      for overdamped and underdamped conditions. A consistent, but small, correction
      for kinetic energy is included as well. A characteristic velocity linearizes the
      turbulent casing shear stress so that an analytical solution for attenuated,
      phase shifted pressure fluctuations fits a single parameter (damping frequency)
      to transducer data from any depth in the casing. Underdamped slug tests of 0.3,
      0.6, and 1 m amplitudes at five transducer depths in a 5.1 cm diameter PVC well
      21 m deep in the Plymouth-Carver Aquifer yield a consistent hydraulic
      conductivity of 1.5 x 10(-3) m/s. The Springer and Gelhar (1991) model
      underestimates the hydraulic conductivity for these tests by as much as 25% by
      improperly ascribing smooth turbulent casing friction to the aquifer. The match
      point normalization of Butler (1998) agrees with our fitted hydraulic
      conductivity, however, when friction is included in the damping frequency.
      Zurbuchen et al. (2002) use a numerical model to establish a similar sensitivity
      of hydraulic conductivity to nonlinear casing friction.

PMID- 15726926
TI  - Mass and flux distributions from DNAPL zones in sandy aquifers.
AB  - At three industrial sites in Ontario, New Hampshire, and Florida,
      tetrachloroethylene (PCE) and trichloroethylene (TCE), released decades ago as
      dense nonaqueous phase liquids (DNAPLs), now form persistent source zones for
      dissolved contaminant plumes. These zones are suspended below the water table and
      above the bottoms of their respective, moderately homogeneous, unconfined sandy
      aquifers. Exceptionally detailed, depth-discrete, ground water sampling was
      performed using a direct-push sampler along cross sections of the dissolved-phase
      plumes, immediately downgradient of these DNAPL source zones. The total plume PCE
      or TCE mass-discharge through each cross section ranged between 15 and 31
      kg/year. Vertical ground water sample spacing as small as 15 cm and lateral
      spacing typically between 1 and 3 m revealed small zones where maximum
      concentrations were between 1% and 61% of solubility. These local maxima are
      surrounded by much lower concentration zones. A spacing no larger than 15 to 30
      cm was needed at some locations to identify high concentration zones, and aqueous
      VOC concentrations varied as much as four orders of magnitude across 30 cm
      vertical intervals. High-resolution sampling at these sites showed that three
      quarters of the mass-discharge occurs within 5% to 10% of the plume cross
      sectional areas. The extreme spatial variability of the mass-discharge occurs
      even though the sand aquifers are nearly hydraulically homogeneous. Depth
      discrete field techniques such as those used in this study are essential for
      finding the small zones producing most of the mass-discharge, which is important
      for assessing natural attenuation and designing remedial options.

PMID- 15726928
TI  - Estimating ground water recharge from topography, hydrogeology, and land cover.
AB  - Proper management of ground water resources requires knowledge of the rates and
      spatial distribution of recharge to aquifers. This information is needed at
      scales ranging from that of individual communities to regional. This paper
      presents a methodology to calculate recharge from readily available ground
      surface information without long-term monitoring. The method is viewed as
      providing a reasonable, but conservative, first approximation of recharge, which
      can then be fine-tuned with other methods as time permits. Stream baseflow was
      measured as a surrogate for recharge in small watersheds in southeastern
      Wisconsin. It is equated to recharge (R) and then normalized to observed annual
      precipitation (P). Regression analysis was constrained by requiring that the
      independent and dependent variables be dimensionally consistent. It shows that
      R/P is controlled by three dimensionless ratios: (1) infiltrating to overland
      water flux, (2) vertical to lateral distance water must travel, and (3)
      percentage of land cover in the natural state. The individual watershed
      properties that comprise these ratios are now commonly available in GIS data
      bases. The empirical relationship for predicting R/P developed for the study
      watersheds is shown to be statistically viable and is then tested outside the
      study area and against other methods of calculating recharge. The method produces
      values that agree with baseflow separation from streamflow hydrographs (to within
      15% to 20%), ground water budget analysis (4%), well hydrograph analysis (12%),
      and a distributed-parameter watershed model calibrated to total streamflow (18%).
      It has also reproduced the temporal variation over 5 yr observed at a well site
      with an average error < 12%.

PMID- 15726929
TI  - Effects of gas generation and precipitates on performance of Fe0 PRBs.
AB  - Long-term reactivity and permeability are critical factors in the performance of
      granular iron permeable reactive barriers (PRBs). Thus it is a topic of great
      practical importance, as well as scientific interest. In this study, four types
      of source solutions (distilled H2O, 10 mg/L TCE, 300 mg/L CaCO3, and 10 mg/L TCE
      + 300 mg/L CaCO3) were supplied to four columns containing a commercial granular
      iron material. In all four columns, gases accumulated to approximately 10% of the
      initial porosity and resulted in declines in permeability of approximately 50% to
      80%. In the columns receiving CaCO3, carbonate precipitates accumulated to
      approximately 7% of the initial porosity, with no apparent decline in
      permeability. The data indicate that precipitates formed initially at the
      influent ends of the columns, reducing the reactivity of the iron in this region.
      As a consequence of the reduced reactivity, calcium and bicarbonate migrated
      further into the column, to precipitate in a region where the reactivity remained
      high. Thus precipitation occurred as a moving front through the columns. The
      results suggest improved methods for PRB design and rehabilitation, and also
      suggest improvements that are needed in the mathematical models developed for
      predicting long-term performance.

PMID- 15726930
TI  - Grid resolution study of ground water flow and transport.
AB  - Three-dimensional grids representing a heterogeneous, ground water system are
      generated at 10 different resolutions in support of a site-scale flow and
      transport modeling effort. These grids represent hydrostratigraphy near Yucca
      Mountain, Nevada, consisting of 18 stratigraphic units with contrasting fluid
      flow and transport properties. The grid generation method allows the stratigraphy
      to be modeled by numerical grids of different resolution so that comparison
      studies can be performed to test for grid quality and determine the resolution
      required to resolve geologic structure and physical processes such as fluid flow
      and solute transport. The process of generating numerical grids with appropriate
      property distributions from geologic conceptual models is automated, thus making
      the entire process easy to implement with fewer user-induced errors. The series
      of grids of various resolutions are used to assess the level at which increasing
      resolution no longer influences the flow and solute transport results. Grid
      resolution is found to be a critical issue for ground water flow and solute
      transport. The resolution required in a particular instance is a function of the
      feature size of the model, the intrinsic properties of materials, the specific
      physics of the problem, and boundary conditions. The asymptotic nature of results
      related to flow and transport indicate that for a hydrologic model of the
      heterogeneous hydrostratigraphy under Yucca Mountain, a horizontal grid spacing
      of 600 m and vertical grid spacing of 40 m resolve the hydrostratigraphic model
      with sufficient precision to accurately model the hypothetical flow and solute
      transport to within 5% of the value that would be obtained with much higher
      resolution.

PMID- 15726932
TI  - Visual Basic programs for spreadsheet analysis.
AB  - A collection of Visual Basic programs, entitled Function.xls, has been written
      for ground water spreadsheet calculations. This collection includes programs for
      calculating mathematical functions and for evaluating analytical solutions in
      ground water hydraulics and contaminant transport. Several spreadsheet examples
      are given to illustrate their use.

PMID- 15726931
TI  - A passive-discrete water sampler for monitoring seepage.
AB  - This paper presents the design of the passive-discrete water sampler (PDWS) which
      has been developed to facilitate investigations of flow partitioning in fractured
      rocks. The PDWS continuously isolates seeping water into discrete samples while
      monitoring the seepage rate. The PDWS was used in a flow and transport experiment
      that investigated fracture-matrix interactions. During the experiment, a mix of
      conservative tracers with significantly different diffusion coefficients (lithium
      bromide [LiBr] and pentafluorobenzoic acid [PFBA]) was introduced along a fault
      located in fractured tuffs, and water seeping through the lower end of the fault
      was collected by the PDWS and analyzed for tracer concentrations. Preliminary
      results from this investigation show that samples of effluent captured by the
      PDWS effectively retained temporal changes in the chemical signature, while
      providing seepage rates.

PMID- 15726933
TI  - The Wisconsin roots of ground water hydrology.

PMID- 15726934
TI  - Intimate partner physical assault before and during pregnancy: how does it relate
      to women's psychological vulnerability?
AB  - Most studies of intimate partner violence tend to be behaviorally focused, with
      scant attention paid to women's perception of vulnerability in their
      relationships. Since past research has linked such feelings and cognitions to
      women's health problems, it is important to examine multiple aspects of
      relationships when studying partner violence. Therefore, this study examines
      women's perceptions of vulnerability as they relate to their experiences of
      physical assault by their partner before and during pregnancy. A sample of 86
      prenatal care patients were interviewed. The women reported their experiences of
      partner physical assault using the Conflict Tactics Scale 2, and they reported
      their perceptions concerning their relationships using the Women's Experiences
      with Battering Scale. Bivariate and multivariate analyses found that experiencing
      intimate partner physical assault was highly predictive of women's perceptions of
      vulnerability and loss of control in their relationships, with women who have
      been in physically violent relationships for longer periods of time being the
      most likely to express such feelings. Given that previous research has found such
      perceptions tied to negative health outcomes, clinicians are urged to evaluate
      their female patients' feelings of vulnerability as well as their experiences of
      intimate partner physical assault.

PMID- 15726935
TI  - Testing three competing hypotheses for explaining lethal violence.
AB  - This study tests three competing hypotheses for explaining lethal violence that
      is conceptualized as the combination of both suicide and homicide. These three
      hypotheses differ on how lethal violence can be expressed as either suicide or
      homicide. Suicide and homicide data, from 1989 to 1991, were obtained from the
      Multiple Cause of Death study conducted by the National Center for Health
      Statistics. A bivariate analysis shows that there is a positive correlation
      between suicide and homicide rates for 458 large counties in the US. A weighted
      least square regression analysis reveals that the attribution hypothesis is
      supported by the results. Counties with a higher degree of others-blame
      worthiness are more likely to express violence as homicide. Neither the
      socialization nor the social disorder hypotheses is supported by the analysis.
      Results of this study suggest that it is fruitful to study both suicide and
      homicide under the same theoretical and empirical framework.

PMID- 15726936
TI  - Criminal history and assault of dating partners: the role of type of prior crime,
      age of onset, and gender.
AB  - Some studies of assaults on intimate partners have found that most of the
      perpetrators are not violent outside the family, which suggests a specialized
      type of crime. However, other studies found domestic violence offenders tend to
      have extensive criminal histories. To further investigate the extent to which
      partner assaults are part of a more general pattern of criminal behavior or a
      specialized type of crime, we studied the dating relationships of 653 university
      students. Thirty-one percent reported assaulting a partner in the previous 12
      months. The rate of assault on partners by females did not differ significantly
      for males (29%) and females (32%). We also found high rates of other self
      reported crime, and much higher rates by males. For example, over one half of the
      male students and almost one third of the female students reported having stolen
      money. The male students reported an average of 3.4 crimes committed, and the
      female students an average of 1.4 crimes. These high crime rates and gender
      differences are consistent with many previous studies. Logistic regression
      analysis revealed that a history of prior criminal acts is associated with an
      increased probability of assaulting a partner. The relationship was greater when
      there was prior violent crime compared to property crime, when there was early
      onset of criminal behavior, and when the offender was female. The implications of
      the findings for understanding partner assaults, criminal careers, and gender
      differences in the etiology of violence against intimate partners are discussed.

PMID- 15726937
TI  - Psychologists' judgments of psychologically aggressive actions when perpetrated
      by a husband versus a wife.
AB  - Research literature suggests that clinical judgments of men's versus women's
      behavior and symptoms typically rate the men as more pathological and dangerous.
      To determine whether this view would extend to assessments of psychologically
      aggressive actions, two separate versions of a survey listing potentially
      psychologically abusive behaviors perpetrated by either a wife toward her husband
      or the identical actions perpetrated by a husband toward his wife were sent to a
      nationwide sampling of practicing psychologists. Results indicated that
      psychologists, irrespective of demographics, rated the husband's behavior as more
      likely to be psychologically abusive and more severe in nature than the wife's
      use of the same actions. Psychologists did not differentially rely on any of the
      three contextual factors (i.e., frequency/duration, intent of the perpetrator,
      and perception of the recipient) to influence their determination that a behavior
      was "psychological abuse" dependent upon whether the initiator of the
      psychological actions was the husband or the wife. Future research could assess
      more directly the rationale for the psychologists' differing views of male versus
      female behavior. In addition, more normative information is needed to inform
      mental health professionals as to the prevalence and severity of psychologically
      aggressive actions in the general population.

PMID- 15726938
TI  - Patterns of mutual and nonmutual spouse abuse in the U.S. Army (1998-2002).
AB  - The pattern and severity of substantiated mutual and nonmutual spouse abuse
      between U.S. Army enlisted personnel and their spouses was determined for 1998 to
      2002. The number of nonmutual and mutual abuse victims was equal in 1998, but by
      2002 there were about twice as many non mutual as mutual victims. The rate per
      thousand of mutual abuse decreased by 58% while that of nonmutual abuse decreased
      by 13%. The rate per thousand of female victims was always greater than male
      victims for non-mutual abuse and the severity of abuse of female victims was
      always more severe than male victims. The active duty female had the highest risk
      of becoming a victim. These patterns of mutual and nonmutual domestic abuse in
      the U.S. Army suggest that prevention and educational approaches could be
      developed that would be useful to prevention specialists and to clinicians as the
      Army pursues avenues to reduce domestic violence.

PMID- 15726939
TI  - Age and vengeance as predictors of mild driver aggression.
AB  - The present study examined the influence of driver age and vengeance on mild
      aggression among drivers with at least 5 years experience. Mild aggression
      decreased with age among low vengeance drivers and changed little across age
      groups among moderately vengeful drivers. However, mild driver aggression
      actually increased with age among highly vengeful drivers. Results are
      interpreted in terms of the aggressive nature of an enduring vengeful attitude.

PMID- 15726940
TI  - Demographic and situational factors affecting injury, resistance, completion, and
      charges brought in sexual assault cases: what is best for arrest?
AB  - This study examines demographic and situational factors in an effort to predict
      whether or not a complainant was injured, used resistance, experienced a
      completed assault, and whether charges were brought against the offender. If the
      accused had consumed alcohol or drugs, he was almost seven times more likely to
      be arrested. The complainant was six times more likely to report rape completion
      if she had consumed alcohol or drugs and if the complainant fell unconscious at
      any time during the attack she was significantly less likely to use a resistance
      strategy. The complainant's use of a compliance strategy at any time during the
      assault positively predicted not using a physical resistance strategy and sexual
      assault completion. The reporting of injury positively predicted use a physical
      resistance strategy and sexual assault completion. If the assault was completed,
      it was less likely that charges were pressed. Implications of these findings are
      discussed, and directions for future research are offered.

PMID- 15726941
TI  - Where to publish family violence research?
AB  - Family violence researchers must weigh numerous factors in deciding where to
      submit their work for publication. The purpose of the present study is to provide
      a useful guide for family violence researchers to make informed decisions about
      publishing their manuscripts. Through an extensive computerized literature
      search, 22 English-language specialty and non-specialty journals that frequently
      publish articles on family violence were identified. Editors or editorial staff
      of these journals were contacted and completed a brief questionnaire about their
      respective journal. Journals varied widely in types of articles accepted for
      publication, target audience, circulation rates, number of issues per year, and
      acceptance rates. Journals generally evidenced high acceptance rates following
      resubmission. Overall, this study identified numerous journals to serve as
      outlets for the theoretical and empirical efforts of family violence researchers.

PMID- 15726942
TI  - Single-wall carbon nanotube coating on a pyroelectric detector.
AB  - Carbon single-wall nanotubes (SWNTs) are studied as the thermal-absorption
      coating on a large area pyroelectric detector. The SWNTs were produced by a laser
      vaporization method and dispersed onto the detector surface by use of a simple
      airbrush technique. The detector was based on a 1-cm-diameter, 60-microm-thick
      lithium tantalate disk having nickel electrodes. We report the spectral
      responsivity of the detector ranging from 600 to 1800 nm, as well as the spatial
      and directional uniformity at 850 nm. Using Drude and Lorentzian dielectric
      functions and an effective medium approximation to obtain the indices of
      refraction of semiconductor and metallic SWNTs, we compared the expected
      theoretical relative responsivity for the two types of tube with the measured
      relative responsivity of the detector. Values of thermal conductivity, specific
      heat, and damage threshold obtained from the literature are compared with
      properties of alternatives for thermal coatings such as gold-black and carbon
      based paint.

PMID- 15726943
TI  - Optical acoustic detector based on a fiber Fabry-Perot interferometer.
AB  - We describe a novel optical acoustic detector based on a bias-controlled fiber
      Fabry-Perot interferometer. The detector has a broad bandwidth from 10 Mhz to a
      few gigahertz and higher sensitivity than conventional systems, which are useful
      for noncontact characterization of microsamples based on laser ultrasound.

PMID- 15726944
TI  - Synthesis of fiber Bragg grating parameters from experimental reflectivity: a
      simplex approach and its application to the determination of temperature
      dependent properties.
AB  - A simple, accurate, and fast method to synthesize the physical parameters of a
      fiber Bragg grating numerically from its reflectivity is proposed and
      demonstrated. Our program uses the transfer matrix method and is based on a
      Nelder-Mead simplex optimization algorithm. It can be applied to both uniform and
      nonuniform (apodized and chirped) fiber Bragg gratings. The method is then used
      to synthesize a uniform Bragg grating from its reflectivity taken at different
      temperatures. It gives a good estimate of the thermal expansion coefficient and
      the thermo-optic coefficient of the fiber.

PMID- 15726945
TI  - Equation-based triangle orientation discrimination sensor performance model based
      on sampling effects.
AB  - An equation-based triangle orientation discrimination (TOD) performance model was
      first developed to focus on staring thermal imagers. Specifically, the spatial
      spectra distribution of a standard triangle pattern is determined. The modulation
      effects of the overall components of the system on a nonperiodic standard
      triangle pattern are analyzed and modeled. The matched filter idea is used to
      characterize quantitatively the spatiotemporal integration of the eye and brain
      to signal, aliasing, and various noise components over a triangle pattern area,
      and the perceived signal-to-noise ratio of the staring thermal imager is derived.
      Further, the TOD performance theoretical model is established. Comparison with
      the experimental results shows that this theoretical model gives a reasonable
      prediction of the TOD performance curve for staring thermal imagers. Although
      more tests and modifications are required, these preliminary results suggest that
      this model can be developed into a model that predicts the TOD for a wide range
      of sensors.

PMID- 15726946
TI  - Design and fabrication of diffractive optical elements by use of gray-scale
      photolithography.
AB  - Diffractive optical elements (DOEs) are key components in the miniaturization of
      optical systems because of their planarity and extreme thinness. We demonstrate
      the fabrication of DOEs by use of gray-scale photolithography with a high-energy
      beam sensitive glass photomask. We obtained DOE lenses with continuous phase
      profiles as small as 800 microm in diameter and 5.9 microm in the outermost
      grating pitch by selecting a suitable optical density for each height level and
      optimizing the process variables. Microlenses patterned with eight levels and
      replicated by UV embossing with the polymer master mold showed a diffraction
      efficiency of 81.5%, which was sufficiently high for the devices to be used as
      optical pickups. The effects of deviations in diffraction efficiency between the
      DOE height and profile design were analyzed.

PMID- 15726947
TI  - Reduction of the distortion of diffractive-gradient-index high-resolution
      objectives.
AB  - The possibility of multiple reductions of the distortion of high-resolution
      monochromats that consist of diffractive and radial gradient-index lenses is
      shown. The desirable effect is achieved by mutual compensation of various order
      members. Design parameters and the field performances of objectives that confirm
      the effectiveness of a method, are presented.

PMID- 15726948
TI  - Multiple surface-plasmon resonance in uniform-waist tapered optical fibers with
      an asymmetric double-layer deposition.
AB  - Novel devices consisting of uniform-waist tapered optical fibers with asymmetric
      double-layer (metal plus dielectric) depositions have been recently proposed as
      refractive-index sensors. We study the properties of light transmission by use of
      this kind of devices, and we specifically perform a detailed study of the
      generation of surface-plasma waves in the structures. We show that multiple
      surface plasmons are excited for specific combinations of the constructive
      parameters of the devices and for specific ranges of the refractive index of the
      surrounding medium. The behavior also depends on the wavelength and the state of
      polarization of the incident light. The use of uniform-waist tapers allows for
      control of constructive parameters and an increase in the interaction length with
      the outer medium. We show how the plasmons are excited in the region of the taper
      waist by a coupling with the cladding modes guided in that area. This
      characterization shows the importance of the presence of a dielectric layer for
      selection of the operating range of the device. The results are useful for the
      design of new sensors.

PMID- 15726949
TI  - Superhydrophobic antireflective silica films: fractal surfaces and laser-induced
      damage thresholds.
AB  - Several superhydrophobic antireflective silica films have been prepared by a
      solgel method that uses hexamethyl-disilizane (HMDS) as a modifier. In a high
      power laser, laser-induced damage thresholds (LIDTs) of 23-30 J/cm2 were obtained
      at 1064-nm wavelength with 1-ns pulse duration. By atomic-force microscopy and
      optical microscopy, the fractal surfaces of films were studied, and multifractal
      spectra (MFSs) were calculated both before and after laser damage. The two-sided
      effect of HMDS on particle growth determined the surface fractal of a particle
      and the multifractal structure of a film's surface. The bigger deltaalpha was,
      both before and after laser damage, the lower the LIDT was. The effect of methyl
      groups should be included in the determination of the MFS of the LIDT.

PMID- 15726950
TI  - Optical properties of reactively sputtered TeOx amorphous films.
AB  - We report on the linear optical properties of TeOx films deposited by radio
      frequency reactive sputtering on fused-silica substrates. The oxygen
      stoichiometry ranges from x = 1.95 to x = 2.75, as experimentally determined by
      Rutherford backscattering. The complex dielectric function of TeOx samples has
      been measured in the range from lambda = 260 nm to lambda = 1700 nm by variable
      angle spectroscopic ellipsometry. All samples are transparent in the visible and
      near infrared. Regarding the refractive index measured at lambda = 1.5 microm,
      delta n variations from 0.5% to 7% were found, with the general trend
      monotonically decreasing with respect to the oxygen content. This opens the
      possibility to easily implement TeOx-based multilayer structures, with a fine
      tuning of the index, which could be of particular interest for applications in
      optical communications.

PMID- 15726951
TI  - Improvement to human-face recognition in a volume holographic correlator by use
      of speckle modulation.
AB  - We show that a speckle-modulation technique can improve the parallelism and the
      recognition accuracy of volume holographic correlators. The object patterns are
      modulated by a speckle pattern generated by a diffuser. These modulated patterns
      are stored as Fourier holograms by use of angular-fractal multiplexing. With the
      speckle modulation the sidelobes are completely suppressed, the cross talk is
      negligible, and the correlation peak becomes a bright sharp spot. Thus higher
      recognition accuracy is achieved. The angular separation between adjacent
      patterns in the multiplexing could be much smaller, resulting in larger capacity
      and higher parallelism of the correlator. Also, this technique can be combined
      with other methods such as wavelet filtering to achieve a large invariant
      tolerance range. Theoretical analysis, numerical evaluation, and experimental
      results are presented to confirm that sidelobes and cross talk are sharply
      suppressed by the speckle modulation.

PMID- 15726952
TI  - Wide-viewing-angle integral three-dimensional imaging system by curving a screen
      and a lens array.
AB  - A wide-viewing-angle integral three-dimensional imaging system made by curving a
      screen and a lens array is described. A flexible screen and a curved lens array
      are incorporated into an integral imaging system in place of a conventional flat
      display panel and a flat lens array. One can effectively eliminate flipped images
      by adopting barriers. As a result, the implemented system permits the limitation
      of viewing angle to be overcome and the viewing angle to be expanded remarkably.
      Using the proposed method, we were able to achieve a viewing angle of 33 degrees
      (one side) for real integral imaging and 40 degrees (one side) for virtual
      integral imaging, which is four times wider than that of the currently used
      conventional techniques. The principle of the implemented system is explained,
      and some experimental results are presented.

PMID- 15726953
TI  - Platform perturbations in above-water radiometry.
AB  - A comparison of above- and in-water spectral measurements in coastal (but
      predominantly Case-1) conditions has shown that the uncertainty in above-water
      determinations of water-leaving radiances made from an offshore tower depends on
      the proximity of the above-water measurement with respect to the side of the
      platform. For purposes of this study the proximity of the sampling platform is
      parameterized as the perpendicular distance (denoted x) from the side of the
      sampling platform to the center of the area on the sea surface observed by the
      sea-viewing sensor, the so-called surface spot, which is set by the field of view
      of the radiometer (or the overlapping fields of view of a multiaperture sensor).
      Two above-water data processing methods were used to create a diagnostic variable
      (formulated for Case-1 waters only but also applicable to Case-2 conditions over
      short time scales) to quantify the presence of superstructure reflections. Based
      on the height of the tower, H, the analyses were partitioned into near- and far
      field data sets (x < H and x > H, respectively). The primary conclusions of the
      radiometric intercomparisons are as follows: (a) the maximum perturbations occur
      very close to the tower ( x/H << 1), and, as x/H increases and approaches 1
      (i.e., as the surface spot becomes as far away as the platform is high), the
      platform perturbations converge toward smaller and smaller values, and (b) within
      the far field (x > H) the platform perturbation is negligible, and a remote
      sensing 5% absolute accuracy objective can be satisfied.

PMID- 15726954
TI  - Effect of external cavity length on self-mixing signals in a multilongitudinal
      mode Fabry-Perot laser diode.
AB  - The effect of external-cavity length on self-mixing signals in a
      multilongitudinal-mode Fabry-Perot laser diode (FP-LD) was investigated
      experimentally. It has been shown that the output waveforms of self-mixing
      signals vary periodically when the length of the external cavity changes. This
      result agrees well with our theoretical calculations for the self-mixing effect
      of two adjacent longitudinal modes in a FP-LD. Moreover, the time-averaged output
      intensities of self-mixing signals has also been measured and compared with
      theoretical analysis.

PMID- 15726955
TI  - Coupled-cavity analysis of the resonant loop mirror: closed-form expressions and
      simulations for enhanced performance lasing.
AB  - A coupled-cavity analysis of the resonant loop mirror with a signal flow graph
      technique is presented. Use of this technique has resulted in simple closed-form
      expressions for reflectance, transmittance, critical coupling, bandwidth,
      finesse, gain threshold, and mode splitting. Application of this device to
      enhance the single longitudinal mode operation of a fiber laser is also proposed.
      Detailed simulation results show a dramatic reduction in bandwidth and a
      threefold enhancement of the free spectral range by use of the vernier effect.
      The formulas and results obtained would also be useful in laser sensors and
      filters.

PMID- 15726956
TI  - Diode-pumped Nd:YAG master oscillator power amplifier with high pulse energy,
      excellent beam quality, and frequency-stabilized master oscillator as a basis for
      a next-generation lidar system.
AB  - A pulsed, diode-laser-pumped Nd:YAG master oscillator power amplifier (MOPA) in
      rod geometry, frequency stabilized with a modified Pound-Drever-Hall scheme is
      presented. The apparatus delivers 33-ns pulses with a maximum pulse energy of 0.5
      J at 1064 nm. The system was set up in two different configurations for
      repetition rates of 100 or 250 Hz. The beam quality was measured to be 1.5 times
      the diffraction limit at a pulse energy of 405 mJ and a repetition rate of 100
      Hz. At 250 Hz with the same pulse energy, the M2 was better than 2.1. The
      radiation is frequency converted with an efficiency of 50% to 532 nm. This MOPA
      system will be the pump laser of transmitters for a variety of high-end, scanning
      lidar systems.

PMID- 15726957
TI  - Optical properties of randomly distributed soot: improved polarimetric and
      intensity scattering functions.
AB  - Reference scattering curves for polarization and intensity produced by aggregates
      and agglomerates of ethylene and kerosene soot are obtained for scattering angles
      in the 10-170 degrees range. The polarization measurements were obtained with the
      Proprietes Optiques des Grains Astronomiques et Atmospheriques instrument for
      particles that levitate in microgravity during parabolic flights and on the
      ground by an air draught technique. The intensity measurements were obtained also
      on the ground with a Laboratoire de Meteorologie Physique nephelometer. The
      maximum polarization is of the order of 80% at a scattering angle of 80 degrees
      at lambda = 632.8 nm and approximately 75% at an angle of 90 degrees at lambda =
      543.5 nm. The polarization increases by approximately 10% when the size of the
      agglomerate increases from 10 microm to a few hundred micrometers. The intensity
      curve exhibits a strong increase at small scattering angles. These reference
      curves will be used in the near future for the detection of stratospheric soot by
      remote-sensing measurement techniques.

PMID- 15726958
TI  - Comparisons of bidirectional reflectance distribution function measurements on
      prepared particulate surfaces and radiative-transfer models.
AB  - To understand the connection between single-particle optics and the optics of a
      closely packed surface, controlled laboratory measurements of bidirectional
      reflectance distribution functions on layers of polymer and glass spheres are
      carried out. The measurements are compared with predictions from five radiative
      transfer models; the Hapke's models, the Lumme-Bowell model, the BRF algorithm of
      Mishchenko et al., and the discrete ordinate radiative transfer. It is found that
      models of strict numerical radiative-transfer equations (RTEs) predict
      measurements well in some regions but have errors in both forward- and backward
      scattering directions. The improved Hapke's model, although it has an anisotropic
      multiple-scattering term, still produces considerable errors compared with the
      strict RTE. The difference can be attributed to the exclusion of a diffraction
      contribution in the Hapke model.

PMID- 15726959
TI  - Quantitative absorption spectroscopy of residual water vapor in high-purity
      gases: pressure broadening of the 1.39253-microm H2O transition by N2, HCl, HBr,
      Cl2, and O2.
AB  - We determined the respective pressure-broadening coefficients of HCl, HBr, Cl2,
      and O2 (expressed relative to that of the reference gas N2) for the
      (v1,v2,v3)J(Ka,Kc) = (0,0,0)3(0,3) --> (1,0,1)2(0,2) rovibrational transition of
      H2 16O that occurs at 1.39253 microm. The experiment used a continuous-wave
      cavity ring-down spectroscopy analyzer to measure the peak absorption losses as a
      function of added moisture concentration. The measured pressure-broadening
      coefficients for HCl, HBr, Cl2, and O2 are, respectively, 2.76, 2.48, 1.39, and
      0.49 times that of the N2 pressure-broadening coefficient, and detection limits
      for water vapor range from 0.22 nmol mol(-1) for O2 matrix gas to 2.3 nmol mol(
      1) for HBr matrix gas. The degradation of the detection limit (relative to the N2
      matrix gas) is ascribed to a pressure-broadening-induced reduction in peak
      absorption cross section and to elevated background loss from the matrix gas.

PMID- 15726960
TI  - Transmission electron microscopy study of enterohemorrhagic Escherichia coli
      O157:H7 in apple tissue.
AB  - We investigated the ability of enterohemorrhagic Escherichia coli O157:H7 to
      spread in wounded apple tissue by transmission electron microscopy. Red Delicious
      apples were wounded with an artist knife (7 mm depth) and either inoculated with
      10 microl per wound of decimally diluted E. coli O157:H7 or submerged into E.
      coli O157:H7 suspended in sterile distilled water and then stored at 37 degrees C
      for 24 h. Transmission electron microscopy showed E. coli O157:H7 formed
      bacterial aggregates near the apple cell walls, and single cells were in close
      proximity to the apple cell wall surfaces and to plasma membranes. E. coli
      O157:H7 presence caused degradation of plasma membranes and release of the
      cytoplasm contents of the apple cortical cells into the central vacuole. Apple
      tissue turgor pressure tests showed that the apple cells infected with E. coli
      O157:H7 isolates were more likely to rupture than the control noninoculated apple
      cells. E. coli O157:H7 cells grown in apple tissue showed the formation of
      granules and vesicles within the bacterial cytoplasma and separation of the
      plasma membranes. Our study shows that E. coli O157:H7 can grow and survive in
      the apple tissue environment by causing degradation of the apple cellular
      components.

PMID- 15726961
TI  - Effect of food matrix and cell growth on PCR-based detection of Escherichia coli
      O157:H7 in ground beef.
AB  - The purpose of this work was (i) to investigate the feasibility of a previously
      reported upstream processing method for PCR template preparation to facilitate
      the detection of Escherichia coli O157:H7 from ground beef and (ii) to assess the
      impact of cell growth (no growth in the matrix versus growth in the matrix) on
      molecular detection limits. Two food matrices (autoclaved and raw ground beef)
      were evaluated in all studies. For no-growth experiments, 10-g meat samples were
      inoculated with 10(2) to 10(7) CFU/g E. coli O157:H7 and then homogenized. The
      homogenates were processed to remove large particulates and inhibitors using a
      two-phase upstream processing method consisting of two sequential centrifugation
      steps, the second of which used titanous hydroxide to facilitate bacterial
      immobilization. After upstream processing, sample concentrates were extracted for
      DNA isolation and amplified by PCR. For growth experiments, 10-g meat samples
      were inoculated at 1 CFU of E. coli O157:H7 per gram, allowed to grow to 10(2) to
      10(7) CFU/g, and then processed for PCR assay. Cell recoveries after upstream
      processing ranged from 15.9 to 77.6% and were not facilitated by the use of
      titanous hydroxide, as compared with a saline control (P > 0.05). Bacterial cell
      recovery and PCR detection limits were similar when comparing autoclaved ground
      beef and raw ground beef, but cell recoveries were highly variable for raw ground
      beef samples in which E. coli O157:H7 cells were allowed to grow before
      processing for detection. Overall, PCR detection limits approximated 10(3) CFU/g
      of ground beef for all treatments. These results indicate that use of model food
      systems may not always provide an accurate replication of real-world conditions
      when evaluating PCR detection limits.

PMID- 15726962
TI  - Detection of Escherichia coli O157 in foods by a novel polymyxin-based enzyme
      linked immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay (ELISA) system was developed using polymyxin
      immobilized in the wells of a microtiter plate as a high-affinity adsorbent for
      Escherichia coli O157 lipopolysaccharide (LPS) antigens. Extracts from cell
      suspensions were reacted with polymyxin-coated microwells followed by
      immunoenzymatic detection of captured LPS antigens using a commercially available
      anti-E. coli O157 antibody-peroxidase conjugate and a 3,3',5,5'
      tetramethylbenzidine substrate. The polymyxin ELISA was highly sensitive and
      specific for E. coli strains bearing the O157 antigen. When this ELISA was
      combined with enrichment, results were in complete agreement with those of
      standard culture techniques for the detection of this pathogen in a variety of
      artificially inoculated and naturally contaminated foods. The polymyxin ELISA is
      a simple and inexpensive assay for E. coli O157 with a 96-well microtiter plate
      format, making this system ideally suited for processing large numbers of
      samples.

PMID- 15726963
TI  - Molecular strategies for the detection, identification, and differentiation
      between enteroinvasive Escherichia coli and Shigella spp.
AB  - A strategy for the detection, identification, and differentiation of
      enteroinvasive Escherichia coli (EIEC) and Shigella spp. has been developed. The
      strategy includes (i) a multiplex PCR for the amplification of two virulence
      genes, i.e., iuc (222 bp) and ipaH (629 bp); (ii) amplification of the ial gene
      (a 1,038-bp amplicon) located within a large plasmid; and (iii) restriction
      fragment length polymorphism (RFLP) of the ial gene amplicon. The multiplex PCR
      provided three patterns. Pattern 1 (iuc-/ ipaH+) was found in 10 (67%) of 15 EIEC
      strains tested, pattern 2 (iuc+/ipaH-) in only 2 (4.4%) of 46 non-EIEC isolates,
      whereas pattern 3 (iuc+/ipaH+) was observed in all Shigella spp. and also in 5
      (33%) of 15 EIEC strains tested. The pattern 3 EIEC strains were all positive for
      the ial gene. The PCR-RFLP of the ial gene amplicon using the endonuclease AclI
      was used to differentiate Shigella spp. from the EIEC strains that belonged to
      pattern 3. The ial gene was present in 21 (38%) of 56 and 6 (40%) of 15 Shigella
      spp. and EIEC strains tested, respectively. The PCR-RFLP of the ial gene amplicon
      divided the strains in two types. Type 1 did not contain the restriction enzyme
      site and was found in 6 (100%) of 6 EIEC strains, 4 (80%) of 5 Shigella boydii,
      and 4 (100%) of 4 Shigella dysenteriae strains tested. Type 2, which gave two
      fragments of 286 and 752 bp, was observed in 5 (83%) of 6 Shigella fiexneri
      strains and 6 (100%) of 6 Shigella sonnei strains. Detection, identification, and
      differentiation of Shigella spp. and EIEC were achieved by analyses of the PCR
      patterns and RFLP types. To our knowledge, this is the first study to demonstrate
      a simple and rapid method for detecting, identifying, and differentiating, at the
      molecular level, Shigella spp. and EIEC strains. This method will have tremendous
      utility as an epidemiological tool and in helping to develop policies, risk
      assessments, and national and international methods for Shigella spp.

PMID- 15726964
TI  - Associations between on-farm and slaughter plant detection of Salmonella in
      market-weight pigs.
AB  - Thirty swine production units in the midwestern United States were studied to
      assess the relationship of herd-level prevalence of Salmonella on the farm prior
      to slaughter versus at slaughter. Fecal samples were collected from 30 pigs on
      each farm within 48 h of slaughter, and 30 ileocecal lymph node samples were
      collected in the same shipment cohort at slaughter. Samples were cultured by
      conventional methods, and Salmonella identity was confirmed by serotyping.
      Overall, 11.7% (n = 105) of the fecal samples and 14.9% (n = 133) of the
      ileocecal lymph node samples were positive for Salmonella. Seventeen of the farms
      (56.7%) had one or more positive fecal samples, and 24 (80.0%) had one or more
      positive ileocecal lymph node samples. Twenty-four recognized serotypes and three
      additional distinct antigenic types were identified. Among all isolates, 56.5%
      had serotypes that were duplicated both on the farm and at slaughter for a
      particular cohort, whereas the remaining samples lacked a duplicate serotype in
      the other sample type. There was a positive correlation in the prevalence of
      Salmonella between fecal samples and ileocecal lymph node samples (Spearman's p =
      0.75; 95% confidence interval [CI], 0.62 to 0.89). Linear regression analysis was
      used to identify two farms that biased the regression estimates. Excluding these
      farms, 62% of the variance in farm slaughter Salmonella prevalence was accounted
      for by on-farm prevalence. The analyses suggest that the prevalence of Salmonella
      spp. at slaughter can be predicted from preslaughter on-farm sampling and vice
      versa.

PMID- 15726965
TI  - Efficacy of acidified sodium chlorite treatments in reducing Escherichia coli
      O157:H7 on Chinese cabbage.
AB  - Efficacy of acidified sodium chlorite for reducing the population of Escherichia
      coli O157:H7 pathogens on Chinese cabbage leaves was evaluated. Washing leaves
      with distilled water could reduce the population of E. coli O157:H7 by
      approximately 1.0 log CFU/g, whereas treating with acidified chlorite solution
      could reduce the population by 3.0 log CFU/g without changing the leaf color. A
      similar level of reduction was achieved by washing with sodium chlorite solution
      containing various organic acids. However, acidified sodium chlorite in
      combination with a mild heat treatment reduced the population by approximately
      4.0 log CFU/g without affecting the color, but it softened the leaves. Moreover,
      the efficacy of the washing treatment was similar at low (4 degrees C) and room
      (25 degrees C) temperatures, indicating that acidified sodium chloride solution
      could be useful as a sanitizer for surface washing of fresh produce.

PMID- 15726966
TI  - Salmonella and raw shell eggs: results of a cross-sectional study of
      contamination rates and egg safety practices in the United Kingdom catering
      sector in 2003.
AB  - This study was prompted by epidemiological investigations of the unusual number
      of Salmonella Enteritidis outbreaks associated with the use of eggs in catering
      premises in England and Wales during 2002. The aims of the study, performed
      between April and May 2003, were to establish the rate of Salmonella
      contamination in raw shell eggs from catering premises, investigate any
      correlation between the origin and type of eggs and the presence of particular
      serotypes or phage types (PTs) of Salmonella, and examine the use of raw shell
      eggs in catering premises in the United Kingdom. A total of 34,116 eggs (5,686
      pooled samples of six eggs) were collected from 2,104 catering premises, most of
      which were eggs produced in the United Kingdom (88%). Salmonella was isolated
      from 17 pools (0.3%) of eggs. Of these, 15 were Salmonella Enteritidis, which
      were further characterized to PTs as follows: PT6 (0.1%), PT4 (0.07%), PT12
      (0.04%), PT1 (0.04%), and PT14b (0.02%). Salmonella Livingstone and Salmonella
      Typhimurium definitive type 7 resistant to ampicillin, streptomycin,
      sulfonamides, and tetracycline were also isolated. The Salmonella contamination
      rate of eggs produced in the United Kingdom appears to have decreased
      significantly since 1995 and 1996. This trend is reflected in the decrease of
      Salmonella Enteritidis and, in particular, Salmonella Enteritidis PT4. The impact
      of the United Kingdom Food Standards Agency's advice on the use of eggs, issued
      in January 2003, is discussed.

PMID- 15726967
TI  - Development and evaluation of an on-line hide decontamination procedure for use
      in a commercial beef processing plantt.
AB  - The hides of cattle are the source of Escherichia coli O157:H7 that contaminates
      beef carcasses during commercial beef processing. Therefore, effective
      interventions that reduce hide contamination should reduce subsequent carcass
      contamination. The first objective of this study was to identify the most
      effective reagents for decontamination of beef hides. Cattle hides draped over
      barrels were used for in vitro experiments to compare the efficacy of washes
      using 1.6% sodium hydroxide, 4% trisodium phosphate, 4% chlorofoam, or 4%
      phosphoric acid, each followed by a rinse step using either water or acidified
      (pH 7.0) chlorine at 200 or 500 ppm. All treatments using a water rinse reduced
      hide coliform counts by 1.5 to 2.5 log CFU/ 100 cm2. Compared with water rinses,
      200 and 500 ppm acidified chlorine rinses increased efficacy by approximately 1.0
      and 2.0 log CFU/100 cm2, respectively. Vacuuming of the treated areas to remove
      excess liquid improved hide cleanliness by an average of an additional 1.0 log
      CFU/100 cm2. The second objective was to evaluate the use of an on-line hide-wash
      cabinet that used a sodium hydroxide wash and a chlorinated (1 ppm) water rinse.
      Hides sampled before entering and after exiting the cabinet had aerobic plate
      counts and Enterobacteriaceae counts that were reduced by 2.1 and 3.4 log CFU/100
      cm2, respectively, and the prevalence of E. coli O157 on hides was reduced from
      44 to 17% when the cabinet was in use. Preevisceration carcass aerobic plate
      counts and Enterobacteriaceae counts were both reduced by 0.8 log CFU/100 cm2,
      and the prevalence of E. coli O157 on preevisceration carcasses was reduced from
      17 to 2% when the cabinet was in use. These results support decontamination of
      hides as an effective means to reduce pathogen contamination of cattle carcasses
      during processing.

PMID- 15726969
TI  - Removal of Pseudomonas putida biofilm and associated extracellular polymeric
      substances from stainless steel by alkali cleaning.
AB  - Alkali (NaOH)-based compounds are commonly used in the food industry to clean
      food contact surfaces. However, little information is available on the ability of
      alkali and alkali-based cleaning compounds to remove extracellular polymeric
      substances (EPS) produced by biofilm bacteria. The objectives of this study were
      to determine the temperature and NaOH concentration necessary to remove biofilm
      EPS from stainless steel under turbulent flow conditions (clean-in-place
      simulation) and to determine the ability of a commercial alkaline cleaner to
      remove biofilm EPS from stainless steel when applied under static conditions
      without heat. Biofilms were produced by growing Pseudomonas putida on stainless
      steel for 72 h at 25 degrees C in a 1:10 dilution of Trypticase soy broth. The
      biofilms were treated using NaOH at concentrations of 1.28 to 6.0% and
      temperatures ranging from 66 to 70 degrees C. Other biofilms were treated with
      commercial alkaline cleaner at 25 or 4 degrees C for 1 to 30 min. Removal of EPS
      was determined by direct microscopic observation of samples stained with
      fluorescent-labeled peanut agglutinin lectin. Treatment with 1.2% NaOH at 66
      degrees C for 3 min was insufficient to remove biofilm EPS. A minimum of 2.5%
      NaOH at 66 degrees C and 2.0% NaOH at 68 degrees C for 3 min were both effective
      for EPS removal. Commercial alkaline cleaner removed over 99% of biofilm EPS
      within 1 min at 4 and 25 degrees C under static conditions. Selection of
      appropriated cleaning agent formulation and use at recommended concentrations and
      temperatures is critical for removal of biofilm EPS from stainless steel.

PMID- 15726968
TI  - An outbreak of Salmonella Munchen in Germany associated with raw pork meat.
AB  - In summer 2001, an outbreak of Salmonella Munchen occurred in Germany. We
      conducted descriptive epidemiology and hypothesis-generating interviews among
      case patients, two retrospective cohort studies, and a case-control study of
      suboutbreaks. We performed pulsed-field gel electrophoresis (PFGE) from selected
      patient isolates and a limited trace-back investigation for analytical purposes.
      Four states were consecutively affected: Saxonia (SX), Brandenburg (BB), Berlin
      (BE), and Baden-Wurttemberg (BW). Although hypothesis-generating interviews
      failed to identify a plausible food item, descriptive data and investigations of
      the suboutbreaks suggested pork meat as a probable source in three states (SX,
      BB, and BE) but not in BW. The PFGE profiles from isolates of case patients in
      the first three states were indistinguishable but differed from PFGE profiles of
      case patients in BW. Trace-back investigation suggested that contamination of
      pork meat occurred early in the rearing-production chain. This outbreak
      demonstrates how contamination early in the production process that can yield
      different end products may complicate multistate outbreaks. Investigation of
      suboutbreaks and use of the trace-back method as investigational tools may be
      useful adjuncts in solving the problem of multistate outbreaks.

PMID- 15726970
TI  - Studies to select appropriate nonpathogenic surrogate Escherichia coli strains
      for potential use in place of Escherichia coli O157:H7 and salmonella in pilot
      plant studiest.
AB  - The response of a potential nonpathogenic surrogate organism to a particular
      treatment should closely mimic the response of the target pathogenic organism. In
      this study, growth characteristics (generation time, lag phase duration, and
      maximum population), pH at stationary phase, and survival characteristics (level
      of attachment and survival on apple surfaces, resistance to hydrogen peroxide
      decontamination treatments, and thermal resistance at 60 degrees C) of 15
      nonpathogenic generic Escherichia coli strains and one nonpathogenic E. coli
      O157:H43 strain were compared with those of two E. coli O157:H7 strains and two
      Salmonella strains. Few differences in growth characteristics or pH at stationary
      phase were evident between nonpathogenic and pathogenic strains tested. However,
      considerably more separation among strains was seen following investigation of
      survival characteristics. E. coli ECRC 97.0152, which does not contain genes
      encoding for known virulence factors associated with E. coli O157:H7, appears to
      be a good surrogate candidate, with growth and survival characteristics similar
      to those of E. coli O157:H7 strains. The less heat-resistant surrogate strains E.
      coli NRRL B-766 and NRRL B-3054 and E. coli ATCC 11775, ATCC 25253, and ATCC
      25922 may be used when attempting to model the heat resistance of Salmonella
      Montevideo G4639 and Salmonella Poona RM 2350, respectively. These surrogate
      strains may be useful for evaluating the efficacy of intervention steps in
      reducing populations of selected strains of E. coli O157:H7 and Salmonella in
      processing environments where these pathogens cannot be introduced.

PMID- 15726971
TI  - Comparison of kinetic models to describe high pressure and gamma irradiation used
      to inactivate Vibrio vulnificus and Vibrio parahaemolyticus prepared in buffer
      solution and in whole oysters.
AB  - Comparisons of different models in inactivation kinetics were conducted on data
      obtained from high-pressure and gamma-irradiation processing. Vibrio vulnificus
      (MO-624) and Vibrio parahaemolyticus (O3:K6 TX-2103) suspended in phosphate
      buffered saline (pH 7.4, 10(7) CFU/ml) were exposed to pressures from 207 to 379
      MPa for 1 to 20 min. Inoculated whole oysters (106 CFU/g) were exposed to
      pressure from 276 to 379 MPa for 1 to 15 min. Pure cultures and inoculated
      oysters (10(6) CFU/g) also were irradiated (gamma irradiation) at doses of less
      than 3 kGy. Four mathematical models, the Bigelow model, Arrhenius equation,
      Fermi equation, and Weibull frequency distributions, were applied to microbial
      survival data, and performances of the different kinetic models were compared.
      Weibull frequency distributions can predict the high-pressure inactivation of
      Vibrio spp. with more accuracy in both pure cultures and inoculated oyster
      samples. The Fermi model provided a better description of gamma-irradiation
      inactivation kinetics compared with the traditional Bigelow model.

PMID- 15726972
TI  - Survival of pathogenic bacteria in pesticide solutions and on treated tomato
      plants.
AB  - The ability of Salmonella, Escherichia coli O157:H7, Listeria monocytogenes, and
      Shigella to survive or grow in pesticide solutions (Ambush 240EC, Benlate T-N-G,
      Bravo 500, Botran 75WP, Captan 80WDG, Parasol, and Vendex 50W) used by the
      horticultural industry was examined. In the laboratory, individual cultures were
      inoculated at 4 log CFU/ml in pesticides diluted with sterile saline to the
      lowest recommended spray concentrations. During 21 degrees C incubation for < or
      =96 h, bacterial survivors in the samples and a control consisting of saline were
      enumerated either by agar surface plating or hydrophobic grid membrane
      filtration. Most formulations tested were somewhat inhibitory to the pathogenic
      bacteria. All inoculated bacteria survived or grew in Bravo 500. Among bacteria
      tested, Salmonella spp. were best able to survive and Listeria spp. were least
      able to survive in pesticide solutions. When the incubation temperature or
      pesticide concentration was increased, survival of Salmonella varied depending on
      the type of formulation. In the field, when a bacterial cocktail containing E.
      coli O157:H7 and Salmonella Enteritidis was added to Bravo 500 at 6 log CFU/ml,
      both organisms were recovered from leaves and fruit skins of sprayed tomato
      plants after the recommended 1 day-to-harvest interval. E. coli and Salmonella
      survived longer on tomato leaves when sprayed in saline (at least 26 and 56 days,
      respectively) than when sprayed in Bravo 500 (>45 h and <15 days, respectively).
      While Salmonella serovars Typhimurium and Heidelberg grew in the fungicide Bravo,
      and Enteritidis grew in the insecticide Vendex within 96 h at 21 degrees C in the
      laboratory, pathogen growth in other pesticide formulations did not occur. Higher
      temperature (< or =30 degrees C) or doubling pesticide concentrations had either
      no or a negative effect on Salmonella Heidelberg survival. Use of unexpired
      pesticide formulations may have contributed to the reduced bacterial survival and
      growth found in the laboratory and during the field trials with Bravo.

PMID- 15726973
TI  - Determination of 5-log pathogen reduction times for heat-processed, acidified
      vegetable brines.
AB  - Recent outbreaks of acid-resistant food pathogens in acid foods, including apple
      cider and orange juice, have raised concerns about the safety of acidified
      vegetable products. We determined pasteurization times and temperatures needed to
      assure a 5-log reduction in the numbers of Escherichia coli O157:H7, Listeria
      monocytogenes, and Salmonella strains in acidified cucumber pickle brines.
      Cocktails of five strains of each pathogen were (separately) used for heat
      inactivation studies between 50 and 60 degrees C in brines that had an
      equilibrated pH value of 4.1. Salmonella strains were found to be less heat
      resistant than E. coli O157:H7 or L. monocytogenes strains. The nonlinear killing
      curves generated during these studies were modeled using a Weibull function. We
      found no significant difference in the heat-killing data for E. coli O157:H7 and
      L. monocytogenes (P = 0.9709). The predicted 5-log reduction times for E. coli
      O157:H7 and L. monocytogenes were found to fit an exponential decay function.
      These data were used to estimate minimum pasteurization times and temperatures
      needed to ensure safe processing of acidified pickle products and show that
      current industry pasteurization practices offer a significant margin of safety.

PMID- 15726974
TI  - Alternative sigma factor sigmaB is not essential for listeria monocytogenes
      surface attachment.
AB  - Listeria monocytogenes is a foodborne pathogen frequently isolated from the food
      processing environment. Multiple lines of evidence suggested a possible role for
      the L. monocytogenes alternative transcription factor sigma B (sigmaB) in surface
      attachment and biofilm formation. Therefore, through plate count and microscopic
      techniques, the L. monocytogenes 10403S strain and an otherwise isogenic
      deltasigB strain were tested for attachment to stainless steel. Analysis of
      microscopic images revealed that after 72 h at 24 degrees C under static
      conditions the tested L. monocytogenes strains attached uniformly to surfaces as
      single cells. Both strains were capable of rapid attachment (i.e., numbers of
      attached cells were essentially the same after either 5 min or 24 h of
      incubation). Numbers of attached deltasigB cells were significantly lower than
      those of the wild-type strain after 48 and 72 h of incubation at 24 degrees C (P
      = 0.001). Similar numbers of the deltasigB strain attached to stainless steel
      regardless of temperature (24 or 37 degrees C); however, deltasigB cells attached
      at higher relative numbers in the presence of 6% NaCl after 48 and 72 h.
      Furthermore, in the presence of Pseudomonas fluorescens, similarly high numbers
      of wild-type and deltasigB cells attached to the surfaces, forming mixed
      biofilms. Our data suggest that sigmaB is not required for initial surface
      attachment of L. monocytogenes.

PMID- 15726975
TI  - Effectiveness of irradiation treatments in inactivating Listeria monocytogenes on
      fresh vegetables at refrigeration temperature.
AB  - Ionizing radiation can be effective in controlling the growth of food spoilage
      and foodborne pathogenic bacteria. This study reports on an investigation of the
      effectiveness of irradiation treatment to eliminate Listeria monocytogenes on
      laboratory-inoculated broccoli, cabbage, tomatoes, and mung bean sprouts.
      Irradiation of broccoli and mung bean sprouts at 1.0 kGy resulted in reductions
      of approximately 4.88 and 4.57 log CFU/g, respectively, of a five-strain cocktail
      of L. monocytogenes. Reductions of approximately 5.25 and 4.14 log CFU/g were
      found with cabbage and tomato, respectively, at a similar dose. The appearance,
      color, texture, taste, and overall acceptability did not undergo significant
      changes after 7 days of postirradiation storage at 4 degrees C, in comparison
      with control samples. Therefore, low-dose ionizing radiation treatment could be
      an effective method for eliminating L. monocytogenes on fresh and fresh-cut
      produce.

PMID- 15726976
TI  - Survival of Listeria monocytogenes in experimental chorizos.
AB  - Chorizos-Mexican-style raw-meat sausages-are a concern in California because
      their production in small ethnic food markets is unregulated. Their formulation
      may cause them to appear cooked to the consumer, who may eat the raw sausage
      without prior proper cooking. Bacterial pathogens in such products may cause
      illness or even death. Survivability of Listeria monocytogenes in chorizos was
      evaluated under different storage conditions selected on the basis of an initial
      survey of uninspected chorizos in California. Sausages were formulated to five
      different initial water activity (aw) levels (0.85, 0.90, 0.93, 0.95, 0.97),
      stored under four conditions (refrigeration, "Ref," 6 to 8 degrees C under
      convective air circulation; room temperature, "RT," 24 to 26 degrees C under
      convective air circulation; hood, "Hd," 24 to 26 degrees C under forced air
      circulation; and incubation, "Inc," 30 to 31 degrees C under convective air
      circulation), and sampled after 1, 2, 4, and 7 days. The initial pH was 4.8 and
      remained near 5.0 from day 1 of the sampling period. An inoculated-pack study
      using a five-strain cocktail of L. monocytogenes was performed twice for each
      initial aw. Results indicated that the three lowest initial aw levels (0.85,
      0.90, 0.93) and the Hd and Inc storage conditions were more effective (P < or =
      0.05) at reducing L. monocytogenes levels in chorizos than the two highest
      initial aw levels (0.95 and 0.97) and the Ref storage condition, irrespective of
      storage time. These results can provide a scientific basis for guidelines given
      to uninspected chorizo producers in California and reduce the risk of foodborne
      illness.

PMID- 15726977
TI  - Levels and enterotoxigenicity of Clostridium perfringens in pozole, tamales, and
      birria.
AB  - A quantitative survey of Clostridium perfringens in typical foods served at local
      restaurants was conducted for 18 months in Guadalajara, Mexico. A total of 151
      samples, including goat's birria (50), pozole (50), and beef tamales (51), were
      collected from small restaurants in Guadalajara. Samples were tested for C.
      perfringens by the most probable number (MPN) method and for mesophilic aerobic
      plate counts (MAPCs) and coliform, yeast, and mold counts by plate count methods.
      Isolates confirmed as C. perfringens were further sporulated and tested for
      cytotoxic or cytotonic effect against Vero cells as an indication of enterotoxin
      production. C. perfringens was detected in 78 (52%) of all samples at
      concentrations that ranged from 2.3 to 5.4 log MPN/g. Average MAPCs were 1.3 to
      2.7 log CFU/g, depending on the type of dish. Coliform counts ranged from less
      than 1.0 to 1.5 CFU/g, and yeast and mold counts were less than 1.0 log CFU/g in
      all cases. A total of 118 isolates of C. perfringens were tested for enterotoxic
      effect on Vero cells; 82 (70%) showed activity against Vero cells. Of them, 31
      isolates induced cell lysis, indicating cytotoxic effect; 41 induced cell
      elongation, indicating cytotonic effect; and 10 produced both cytotoxic and
      cytotonic effect. Dilution of the bacterial filtrates that were still producing
      an effect on Vero cells ranged from 1:80 to 1:5,120. These results underscore the
      importance of determining enterotoxigenicity when testing for C. perfringens in
      foods.

PMID- 15726978
TI  - Development of a model to predict growth of Clostridium perfringens in cooked
      beef during cooling.
AB  - The objective of this work was to develop a new model to predict the growth of
      Clostridium perfringens in cooked meat during cooling. All data were collected
      under changing temperature conditions. Individual growth curves were fit using
      DMFit. Germination outgrowth and lag (GOL) time was modeled versus temperature at
      the end of GOL using conservative assumptions. Each growth curve was used to
      estimate a series of exponential growth rates at a series of temperatures. The
      squareroot model was used to describe the relationship between the square root of
      the average exponential growth rate and effective temperature. Predictions from
      the new model were in close agreement with the data used to create the model.
      When predictions from the model were compared with new observations, fail
      dangerous predictions were made a majority of the time. When GOL time was
      predicted exactly, many fail-dangerous predictions shifted toward the fail-safe
      direction. Two important facts regarding C. perfringens should impact future
      modeling research with this organism and may have broader food safety policy
      implications: (i) the normal variability in the response of the organism from
      replicate to replicate may be quite large (1 log CFU) and may exceed the current
      U.S. Food Safety Inspection Service performance standard, and (ii) the accuracy
      of the GOL time model has a profound influence upon the overall prediction, with
      small differences in GOL time prediction (approximately 1 h) having a very large
      effect on the predicted final concentration of C. perfringens.

PMID- 15726979
TI  - Presence of Bacillus cereus in street foods in Gaborone, Botswana.
AB  - The purpose of this study was to evaluate the microbiological safety and quality
      of street foods sold in Gaborone, Botswana. A total of 148 point-of-sale
      composite street food samples were bought and analyzed between June 2001 and May
      2002. The analysis focused on the level of contamination of various street foods
      with Bacillus cereus. The B. cereus (vegetative and spores), total spore, and
      total viable counts were determined on all the samples. Also B. cereus isolates
      from 444 individual point-of-sale food samples were characterized with respect to
      their biochemical profiles and enterotoxigenic properties. The B. cereus
      contamination rate for point-of-sale foods was 65%. The B. cereus counts ranged
      from not detectable to levels as high as 9.1 log CFU/g. Despite the high rate of
      contamination of some samples, generally, most samples had B. cereus counts of
      less than 4 log CFU/g; hence, they were of acceptable microbiological quality.
      Bacillus diarrheal enterotoxin was detected from 52 isolates from individual
      portions of meals using the B. cereus enterotoxin reversed passive latex
      agglutination kit. Results of the assay revealed that 59.6% of the B. cereus
      isolates were enterotoxigenic. Most of the enterotoxigenic isolates were obtained
      from vegetable samples.

PMID- 15726980
TI  - Antibiotic susceptibility of bacteria isolated from pasteurized milk and
      characterization of macrolide-lincosamide-streptogramin resistance genes.
AB  - The presence of antibiotic-resistant bacteria in pasteurized milk was detected by
      plating 18 milk samples on selective media containing beta-lactams, macrolides,
      or a glycopeptide. Most samples contained gram-positive bacteria that grew on
      agar plates containing oxacillin, erythromycin, and/or spiramycin. The disk
      diffusion method confirmed resistance to erythromycin and/or spiramycin in 86 and
      65% of the coryneform bacteria and Micrococcaceae tested, respectively. PCR and
      sequence analysis revealed the presence of an ermC gene in 2 of the 25
      Micrococcaceae strains investigated for their resistance to erythromycin and/or
      spiramycin. None of the 14 corynebacteria strains resistant to erythromycin
      and/or spiramycin harbored the erm(X) gene. No gene transfer could be
      demonstrated between the two erm(C) staphylococcal isolates and recipient strains
      of Enterococcus faecalis JH2-2 or Staphylococcus aureus 80CR5.

PMID- 15726981
TI  - Combined effects of coating, modified atmosphere packaging, and gamma irradiation
      on quality maintenance of ready-to-use carrots (Daucus carota).
AB  - The objective of this study was to evaluate the effect of an edible coating
      combined with modified atmosphere (MA; 60% O2, 30% CO2, and 10% N2) packaging and
      gamma irradiation on the microbiological stability and physicochemical quality of
      minimally processed carrots. A coating based on calcium caseinate and whey
      protein isolates was used. Coated and uncoated peeled minicarrots were packed
      under the MA or air (78.1% N2, 20.9% O2, and 0.036% CO2), irradiated at 0.5 or 1
      kGy, and stored at 4 +/- 1 degrees C for 21 days. Samples were evaluated
      periodically for aerobic plates counts (APCs) and physicochemical properties
      (firmness, white discoloration, and whiteness index). Gamma irradiation did not
      significantly affect the physicochemical properties of the carrots (P > 0.05).
      Microbiological analysis revealed that for uncoated carrots irradiation at 0.5
      and 1 kGy under air and MA reduced the APCs by 3.5 and 4 log CFU/g and by 4 and
      4.5 log CFU/g, respectively. For coated carrots, irradiation at 0.5 and 1 kGy
      under air and MA reduced the APCs by 4 and 4.5 log CFU/g and by 3 and 4.25 log
      CFU/g, respectively. The coating was able to protect carrots against dehydration
      during storage under air. Coating and irradiation at 1 kGy were also able to
      protect carrot firmness during storage under air. MA packaging retarded whitening
      of uncoated carrots but had a detrimental effect on firmness. The edible coating
      used in this study did not significantly inhibit (P > 0.05) microbial growth on
      carrots.

PMID- 15726982
TI  - A comparison of different processing methods for picked blue crab (Callinectes
      sapidus).
AB  - Five methods for producing picked crab meat from cooked blue crab (Callinectes
      sapidus) were evaluated for internal food temperatures and bacterial numbers at
      various process points. Whole shell-on crabs, crab cores ("backed" crabs with
      carapace removed), and crab meat samples were analyzed for standard plate count,
      total coliforms, fecal coliforms, Escherichia coli, and Staphylococcus aureus.
      For three of the processes, crabs were backed and washed a substantial time
      before picking; one of the processes used an ice slush dip to cool cooked crabs.
      Except for a single crab sample, bacteria were not isolated from crab and core
      samples. Standard plate count, E. coli, and S. aureus in crab meat samples from
      the different processes were statistically the same. Bacterial numbers in fresh
      picked crab meat samples exposed to an ambient temperature of 20 to 21.1 degrees
      C for 1.5 and 3.5 h and stored at 1 degrees C for 3 to 4 days and 7 to 8 days did
      not significantly differ (P < 0.05).

PMID- 15726983
TI  - Computational fluid dynamics analysis for process impact assessment during
      thermal pasteurization of intact eggs.
AB  - Transient temperature and albumen velocity profiles during thermal pasteurization
      of intact eggs were studied using a commercial computational fluid dynamics (CFD)
      package. Simulated temperature profiles were in close agreement with experimental
      data for eggs of different sizes. Convective heat transfer only occurred in the
      egg white fraction, and conductive heat transfer only occurred in the yolk. For
      process assessment, a generally accepted kinetic inactivation model for
      Salmonella Enteritidis was incorporated into the CFD analysis. Minimum process
      times and temperatures needed to provide equivalent pasteurization at 5-log
      reductions of the target microorganism were obtained on a theoretical basis. The
      combination of CFD analysis and inactivation kinetics can be very useful for
      assessing pasteurization of intact eggs and can enable processors to gain a
      better understanding of these processes and to establish process conditions for
      consumer-safe eggs.

PMID- 15726984
TI  - Combined use of two single-component enzymatic time-temperature integrators:
      application to industrial continuous rotary processing of canned ravioli.
AB  - Two original, highly dehydrated, small single-component enzymatic time
      temperature integrator (TTI) systems, TTIL and TTIs, were prepared. Their z
      values were 13.9 and 16.4 degrees C, respectively, and they were based on
      Bacillus licheniformis alpha-amylase and Bacillus subtilis alpha-amylase,
      respectively. The isothermal calibration of these two TTIs revealed that (i) they
      can be used in the temperature range of 100 to 140 degrees C, (ii) results can be
      read within 5 min, and (iii) they can be used individually for the measurements
      of process values 13.9 degrees CF121.1 degrees C and 16.4 degrees CF121.1 degrees
      C up to 98 min and 85 min, respectively. Because these two TTIs have different z
      values above 10 degrees C, they could be used in combination with the
      multicomponent TTI concept to estimate process values 10 degrees CF121.1 degrees
      C inside particles of a solid or liquid food submitted to rotary processing.
      Raviolis in tomato sauce sterilized in an industrial-scale reel and spiral
      continuous retort were examined in this study. Two methods, based on the
      combination of a one-dimensional explicit finite difference heat-transfer model
      with the experimental responses of the TTIs, were used to take into account the
      possible deviations in evaluation of 10 degrees CF121.1 degrees C values. A
      process value 10 degrees CF121.1 degrees C of 23.6 min with a standard deviation
      of 1.5 min was determined inside raviolis using the multicomponent TTI approach,
      and a process value 10 degrees CF121.1 degrees C of 33.6 min with a standard
      deviation of 1.5 min inside the sauce was calculated from the temperature
      recording data.

PMID- 15726985
TI  - Extended study on the influence of z-value(s) of single and multicomponent time
      temperature integrators on the accuracy of quantitative thermal process
      assessment.
AB  - The possibilities and limitations of single- and multicomponent time-temperature
      integrators (TTIs) for evaluating the impact of thermal processes on a target
      food attribute with a Ztarget value different from the zTTI value(s) of the TTI
      is far from sufficiently documented. In this study, several thousand time
      temperature profiles were generated by heat transfer simulations based on a wide
      range of product and process thermal parameters and considering a Ztarget value
      of 10 degrees C and a reference temperature of 121.1 degrees C, both currently
      used to assess the safety of food sterilization processes. These simulations
      included 15 different Ztarget=10 degrees CF121.1 degrees C values in the range 3
      to 60 min. The integration of the time-temperature profiles with ZTTI values of
      5.5 to 20.5 degrees C in steps of 1 degrees C allowed generation of a large
      database containing for each combination of product and process parameters the
      correction factor to apply to the process value FmultiTTI, which was derived from
      a single- or multicomponent TTI, to obtain the target process value 10 degrees
      CF121.1 degrees C. The table and the graph results clearly demonstrated that
      multicomponent TTIs with z-values close to 10 degrees C can be used as an
      extremely efficient approach when a single-component TTI with a z-value of 10
      degrees C is not available. In particular, a two-component TTI with z1 and z2
      values respectively above and below the Ztarget value (10 degrees C in this
      study) would be the best option for the development of a TTI to assess the safety
      of sterilized foods. Whatever process and product parameters are used, such a TTI
      allows proper evaluation of the process value 10 degrees CF121.1 degrees C.

PMID- 15726986
TI  - Inactivation of pathogens inoculated into prepared seafood products for
      manufacturing kimbab, steamed rice rolled in dried seaweed, by gamma irradiation.
AB  - Three prepared seafood products for manufacturing a laver (dried seaweed) roll, a
      traditional and rapidly growing ready-to-eat meal in Korea, were selected and the
      effects of irradiation treatment for eliminating pathogens of public health
      significance were investigated. The pathogens tested were Salmonella Typhimurium,
      Escherichia coli, Staphylococcus aureus, and Listeria ivanovii. The radiation
      sensitivity (D10-values or the dose required to inactivate 90% of a population)
      of these organisms ranged from 0.23 to 0.62 kGy in imitation crab leg, 0.31 to
      0.44 kGy in surimi gel, and 0.27 to 0.44 kGy in dried seaweed. The growth of all
      four test organisms inoculated (10(8) CFU/g) into these foods was inhibited by
      irradiation during 24 h of postirradiation storage regardless of the temperature
      (10, 20, and 30 degrees C). L. ivanovii was not detected after a 3-kGy treatment,
      but the other pathogens were not detected following irradiation at 2 kGy. These
      studies indicated that low-dose irradiation (2 kGy or less) of prepared seafood
      materials can keep them microbiologically safe before manufacturing a ready-to
      eat prepared meal, a laver roll.

PMID- 15726987
TI  - Prevalence and antibiotic resistance profiles of Escherichia coli O157:H7 in beef
      products from retail outlets in Gaborone, Botswana.
AB  - Four hundred meat samples (134 meat cubes, 133 minced meat, 133 fresh sausages)
      were collected from 15 supermarkets and butcheries in Gaborone, Botswana, between
      the summer months of October 2002 and March 2003. Samples were assayed for
      Escherichia coli O157 by selective enrichment in modified E. coli broth
      containing novobiocin, followed by immunomagnetic separation and plating onto
      sorbitol MacConkey agar supplemented with potassium tellurite. The isolates were
      biochemically and serologically confirmed by API 20E and O157 antisera,
      respectively. The prevalence rates for E. coli O157 were 5.22% in meat cube
      samples, 3.76% in minced meat samples, and 2.26% in fresh sausages. The isolates
      showed single, double, and triple antibiotic resistance. Fifty-three percent of
      them were resistant to cephalothin. Resistance was also recorded for sulphatriad
      (33%), colistin sulphate (26%), streptomycin (0.7%), and tetracycline (26%). It
      is recommended that the cause for antibiotic resistance be investigated using a
      larger number of samples from cattle, especially from ranching areas of the
      country.

PMID- 15726988
TI  - Simultaneous detection of listeria monocytogenes in chicken meat enrichments by
      PCR and reverse-transcription PCR without DNA/RNA isolation.
AB  - Environmental and food samples can be analyzed using PCR and reverse
      transcription (RT)-PCR techniques to discriminate between viable and nonviable
      cells of bacterial pathogens. Here, we describe the use of a commercial lysis
      buffer, initially designed for mammalian cells, that permits the rapid extraction
      of bacterial DNA and RNA. The buffer is an RT-PCR-compatible lysis solution in
      which RNA is stable and can be frozen for later use. RT-PCR is carried out
      directly after DNase I treatment of crude bacterial lysates using rTth polymerase
      for RT-PCR in a single tube. Untreated lysate is used for standard PCR. The
      procedure permits the amplification of either mRNA or DNA of Listeria
      monocytogenes at a level similar to that obtained with purified nucleic acids.
      Using lysates obtained with this buffer, nested PCR and RT-PCR assays detected
      low numbers of L. monocytogenes cells from artificially contaminated chicken meat
      samples. The simplicity of this system may foster the development of similar
      buffers specifically designed for bacteria to improve RNA detection methods that
      can be performed in parallel with DNA analysis. The use of a single buffer
      decreases the time needed for analysis, is amenable to automation and real-time
      assays, and might be adaptable to all bacteria and amplification methods.

PMID- 15726989
TI  - Incidence of Listeria monocytogenes in raw seafood products in Japanese retail
      stores.
AB  - The incidence of Listeria monocytogenes in raw fish, shellfish, and fish roe was
      investigated in seafood products collected from randomly selected retail stores
      in and around Tokyo, Japan. Of the 10 samples of 208 examined found positive for
      L. monocytogenes by mini-VIDAS LMO, seven were fish roe (cod, salmon) and three
      were minced tuna. Three serotypes (1/2a, 1/2b, 3b) were detected among the
      isolated strains; serotype 1/2a was predominant (8 of 10).

PMID- 15726990
TI  - Occurrence of mycotoxin in Farro samples from southern Italy.
AB  - The occurrence of nine mycotoxins and of contamination by pre- and postharvest
      fungal pathogens of cereals was investigated in samples of stored Triticum
      monococcum L., Triticum dicoccon Schrank (emmer), and Triticum spelta L. (spelt).
      In Italy, all three species are collectively referred to as farro. The samples
      examined were harvested in summer 2000 from eight different sites in southern
      Italy. Conventional fluorimetric and diode array-based high-performance liquid
      chromatography (HPLC) analyses and HPLC-mass spectrometry analyses were used to
      identify fumonisin B1 in five samples (up to 70.00 microg/ kg), ochratoxin A in
      seven samples (up to 4.07 microg/kg), and beauvericin in three samples (up to
      4.44 mg/kg). Enniatin B was detected in one sample (30.00 microg/kg), but no
      zearalenone or fusaproliferin was found. Deoxynivalenol and aflatoxins were not
      evaluated. The potentially mycotoxigenic fungal species detected were Alternaria
      alternata, Fusarium proliferatum, Fusarium tricinctum, Penicillium verrucosum,
      and Penicillium chrysogenum. This is the first report of the natural occurrence
      of mycotoxins in farro samples.

PMID- 15726992
TI  - Bacteriophages as biocontrol agents in food.
AB  - Bacteriophages possess attributes that appear to be attractive to those searching
      for novel ways to control foodborne pathogens and spoilage organisms. These
      phages have a history of safe use, can be highly host specific, and replicate in
      the presence of a host. Campylobacter, Salmonella, and Listeria monocytogenes and
      various spoilage organisms have responded to phage control on some foods.
      However, the use of phages as biocontrol agents is complicated by factors such as
      an apparent requirement for a threshold level of host before replication can
      proceed and by suboptimal performance, at best, at temperatures beneath the
      optimum for the host. This review is a summary of the information on these issues
      and includes brief descriptions of alternative phage-based strategies for control
      of foodborne pathogens.

PMID- 15726991
TI  - Mitochondrial cytochrome b DNA sequence variations: an approach to fish species
      identification in processed fish products.
AB  - The identification of fish species in food products is problematic because
      morphological features of the fish are partially or completely lost during
      processing. It is important to determine fish origin because of the increasing
      international seafood trade and because European Community Regulation 104/2000
      requires that the products be labeled correctly. Sequence analysis of PCR
      products from a conserved region of the cytochrome b gene was used to identity
      fish species belonging to the families Gadidae and Merluccidae in 18 different
      processed fish products. This method allowed the identification of fish species
      in all samples. Fish in all of the examined products belonged to these two
      families, with the exception of one sample of smoked baccala (salt cod), which
      was not included in the Gadidae cluster.

PMID- 15726993
TI  - The ethics of intellectual property rights in biomedicine and biotechnology: an
      introduction.

PMID- 15726994
TI  - The ethics activities of the World Medical Association.
AB  - Since its formation in 1947, the World Medical Association (WMA) has been a
      leading voice in international medical ethics. The WMA's principal ethics
      activity over the years has been policy development on a wide variety of issues
      in medical research, medical practice and health care delivery. With the
      establishment of a dedicated Ethics Unit in 2003, the WMA's ethics activities
      have intensified in the areas of liaison, outreach and product development.
      Initial priorities for the Ethics Unit have been the review of paragraph 30 of
      the Declaration of Helsinki, the expansion of the Ethics Unit section of the WMA
      website and the development of an ethics manual for medical students everywhere.

PMID- 15726995
TI  - The growing complexity of international policy in intellectual property.
AB  - Intellectual property has historically been a self-contained policy at the
      international level. With the introduction of the TRIPs Agreement in 1994 and
      developments since the conclusion of the TRIPs Agreement, the relationship
      between intellectual property policy and other areas of public policy has become
      much more complex and interactive. This shift reflects the centrality of
      intellectual property in the knowledge economy, the rapid development of enabling
      technologies, notably the Internet and biotechnology, and the advent of the
      networked society. The consequences of this shift are manifold and herald the
      increased sophistication and complexity that may be expected of intellectual
      property regimes in the knowledge economy.

PMID- 15726996
TI  - Patenting humans: clones, chimeras, and biological artifacts.
AB  - The momentum of advances in biology is evident in the history of patents on life
      forms. As we proceed forward with greater understanding and technological control
      of developmental biology there will be many new and challenging dilemmas related
      to patenting of human parts and partial trajectories of human development. These
      dilemmas are already evident in the current conflict over the moral status of the
      early human embryo. In this essay, recent evidence from embryological studies is
      considered and the unbroken continuity of organismal development initiated at
      fertilization is asserted as clear and reasonable grounds for moral standing.
      Within this frame of analysis, it is proposed that through a technique of Altered
      Nuclear Transfer, non-organismal entities might be created from which embryonic
      stem cells could be morally procured. Criteria for patenting of such non
      organismal entities are considered.

PMID- 15726997
TI  - Industry, innovation and social values.
AB  - Remaining important tasks in finding and developing new drugs and vaccines for
      HIV/AIDS, malaria, cancer and other diseases require continued industry research
      and development. Industry's research and development pipeline has produced drugs
      that have saved AIDS victims previously facing certain death, but still no cure
      nor vaccine is yet available. Experience with the process of research and
      development indicates that it requires more than a decade of development to
      produce a new drug with costs in the hundreds of millions of dollars.
      Intellectual property protection is critically important in assuring that drug
      development continues. Partnerships between industry and the public sector have
      increased access to new therapies in developing countries and promise to enhance
      access to both patented and generic medicines in the future.

PMID- 15726998
TI  - Medicine and pharmacy--facts and myths about the development of an innovative
      pharmaceutical industry in Poland.
AB  - Innovation is fundamental to the pharmaceutical industry and a key to
      improvements in healthcare. Its effectiveness depends on huge, constant
      investments in research. This innovative industry directly affects the course of
      studies in healthcare and medicine. Its efforts translate directly into the
      length and quality of our lives. For several years now, the progress underway in
      pharmaceutical industry has produced measurable benefits. Doctors have new
      pharmaceuticals at their disposal, including many types of antibiotics and anti
      viral drugs, vaccines and a wide range of drugs which save lives or make them
      more comfortable. In the near future, ever more efficient cures for neoplastic,
      rheumatic, neurological, psychic, metabolic, circulatory or respiratory diseases
      can be expected. Innovation is necessary. The human population is ageing, and the
      task of an innovative pharmaceutical industry is to keep it in a good condition.
      The use of innovative drugs can translate directly into lowering the costs of
      illness. A continuous reduction in spending on healthcare has been observed. The
      costs of inventing an innovative drug are enormous though (US dollar 800
      million), and studies on a new drug last between 10 and 13 years. An essential
      element in recovering the incurred costs and ensuring funds needed for new
      research is protection by patent. Innovative pharmaceutical companies in Poland
      are committed to increasing the competitiveness and sustaining the development of
      not only the market, but also the entire pharmaceutical sector. It is a group of
      companies of crucial importance to the Polish healthcare system, as it influences
      improvement in the quality of medical services. Through their investments and
      spending on research and development, innovative companies accelerate economic
      growth. In Poland, the innovative pharmaceutical industry is represented by the
      Association of Pharmaceutical Companies Representatives in Poland (SPFFwP).

PMID- 15726999
TI  - Making human research safe: why we cannot afford to fail.
AB  - This paper was given as a keynote address at the International Conference on
      Ethics of Intellectual Property Rights and Patents held in Warsaw, Poland on
      April 23-24, 2004. The address was the introductory presentation to the important
      topic of protecting individuals who participate in research as research subjects.

PMID- 15727000
TI  - Surgical patents and patients--the ethical dilemmas.
AB  - It is obvious that every inventor should be rewarded for the intellectual effort,
      and at the same time be encouraged to successively improve his or her discovery
      and to work on subsequent innovations. Patents also ensure that patent owners are
      officially protected against intellectual piracy, but protection of intellectual
      property may be difficult to accomplish. Nevertheless, it all comes down to this
      basic question: Does a contradiction exist between medical ethics and the
      "Medical and Surgical Procedure Patents" system? It may well turn out that
      medical-procedure patents can have a negative influence on the standard of
      medical care. Medical-method patents may also interfere with the physician
      patient relationship. At present, physicians do not question the usefulness of
      patent protection for medicines, biotechnology, equipment and devices, but they
      strongly oppose it for surgical procedures.

PMID- 15727001
TI  - Patents and ethics: is it possible to be balanced?
AB  - In this presentation, principles of ethics are confronted with the desire of the
      inventor to make a profit. To this end the presentation is focused on patent
      protection. Patents should guarantee the return of an inventor's investment and
      profit and, on the other side, ensure availability--by patent disclosure--of the
      invention for the society when the patent terminates. Recent patent applications
      made by inventors are infringing this principle and societies are paying an
      unexpected price for these practices. Patent claims are too broad and disclosures
      too poor. Extreme examples will be discussed.

PMID- 15727002
TI  - Ethical and legal aspects in teaching students of medicine.
AB  - Due to the rapid advances in medical technology, medical students are now being
      faced with increasingly complex and unparalleled ethical and practical dilemmas
      during their training. The new and future challenges of high-tech medicine demand
      improvements in current medical education, not only by meeting the needs of
      students through humanized training programs, but also by involving them in
      finding solutions to the ethical and legal quandaries they encounter. Today's
      students of medical universities must acquire knowledge and understanding of the
      ethical and legal issues relevant to the practice of medicine, and we have to do
      everything possible to introduce these students to the current discussions on
      more or less controversial ethical and legal topics. Although final answers may
      not be found, the very discussion, argumentation, and awakening of students'
      interest should become an essential part of the core curriculum of every doctor.

PMID- 15727003
TI  - Can drug patents be morally justified?
AB  - This paper offers a few elements of an answer to the question to what extent drug
      patents can be morally justified. Justifications based on natural rights,
      distributive justice and utilitarian arguments are discussed and criticized. The
      author recognizes the potential of the patents to benefit society but argues that
      the system is currently evolving in the wrong direction, particularly in the
      field of drugs. More than a third of the world's population has no access to
      essential drugs. The working of the patent system is an important determinant of
      access to drugs. This paper argues that drug patents are not easily justified and
      that the 'architecture' of the patent system should be rethought in view of its
      mission of benefiting society.

PMID- 15727004
TI  - Some ethical and legal issues in Germany involving informed consent and
      patenting.
AB  - This paper elaborates on discussions in Germany regarding some of the ethical and
      legal issues in the area of the use and patenting of inventions involving human
      tissue. The issues discussed pertain to the benefits and problems regarding
      informed consent and the issue of property rights as they relate to the donation
      of cells and tissue.

PMID- 15727005
TI  - The immoral gene: does it really exist?
AB  - Over the last years several European patents were opposed for protecting
      technology violating the morality requirement under Article 53(a) EPC. Attempts
      have been made by the Appeal Boards of the European Patent Office (EPO), as well
      as by amendments introduced into the Implementing Regulations of the European
      Patent Convention (EPC), to address this sensitive patentability requirement more
      precisely. The most recent hot topic coming up in this context is the
      patentability of stem cells. It is to be expected that this discussion will still
      go on in the field of biotechnological inventions for the next several years.

PMID- 15727006
TI  - Ethics and patentability in biotechnology.
AB  - The systems of patent rights in force in Europe today, both at the level of
      national law and on the regional level, contain general clauses prohibiting the
      patenting of inventions whose publication and exploitation would be contrary to
      "ordre public" or morality. Recent years have brought frequent discussion about
      limiting the possibility of patent protection for biotechnological inventions for
      ethical reasons. This is undoubtedly a result of the dynamic development in this
      field in the last several years. Human genome sequencing, the first successful
      cloning of mammals, and the progress in human stem cell research present humanity
      with many new questions of an ethical nature. Directive 98/44 of the European
      Parliament and of the Council of July 6, 1998, on the Legal Protection of
      Biotechnological Inventions created a new basis for patent protection in this
      field of technology. Based on the European experience to now, however, it must be
      said that patent law is not the right place to legislate the consequences of the
      morality of an invention.

PMID- 15727008
TI  - Property rights and genetic engineering: developing nations at risk.
AB  - Eighty percent of (commercial) genetically engineered seeds (GES) are designed
      only to resist herbicides. Letting farmers use more chemicals, they cut labor
      costs. But developing nations say GES cause food shortages, unemployment,
      resistant weeds, and extinction of native cultivars when "volunteers" drift
      nearby. While GES patents are reasonable, this paper argues many patent policies
      are not. The paper surveys GE technology, outlines John Locke's classic account
      of property rights, and argues that current patent policies must be revised to
      take account of Lockean ethical constraints. After answering a key objection, it
      provides concrete suggestions for implementing its ethical conclusions.

PMID- 15727007
TI  - Ethico-legal issues in biomedicine patenting: a patent professional viewpoint.
AB  - Over the last two decades, the ethical implications of patents for biological
      materials and processes have been the subject of spirited public debate between
      the many individuals and groups on which the patent system impacts. Whereas
      copyright, trade marks, and other species of Intellectual Property Rights (IPR)
      are widely acceptable, the patent system evokes criticism from many quarters,
      especially in relation to the legal protection of inventions in the Life
      Sciences. Some of these criticisms expressed by prestigious public organisations
      are addressed here from the patent professional standpoint.

PMID- 15727009
TI  - Observations on a meeting on the ethics of intellectual property rights and
      patents.

PMID- 15727010
TI  - Meeting of professions.

PMID- 15727012
TI  - Dad's here.

PMID- 15727011
TI  - At the sharp end.

PMID- 15727013
TI  - Faces of the future.

PMID- 15727014
TI  - An educating pioneer.

PMID- 15727015
TI  - Guided by love.

PMID- 15727016
TI  - Responding to international disasters.
AB  - Large-scale disasters attract broad coverage by the media and images of death and
      destruction circulate worldwide in minutes. This prompts the authorities in
      disaster-stricken areas to request external medical teams, and well-intentioned
      countries and aid organisations dispatch them to offer care for the victims
      (World Health Organization/Pan American Health Organization (WHO/PAHO) 2004a).
      This article provides information on disaster management for those with an
      interest in responding to international disasters such as the Indian Ocean
      tsunami in December 2004.

PMID- 15727017
TI  - Supporting people with severe myalgic encephalomyelitis.
AB  - This article aims to raise nurses' awareness of myalgic encephalomyelitis (ME)
      also known as chronic fatigue syndrome (CFS). Key symptoms are presented along
      with possible service responses and treatment options. It emphasises that this
      condition is often misunderstood but that it can be serious and more research is
      needed to promote better understanding of the physical symptoms.

PMID- 15727018
TI  - The rational use of psychoactive substances.
AB  - Health professionals have a responsibility to ensure the rational use of
      prescribed psychoactive medicines. The appropriate use of these drugs has become
      a cause for concern in the U.K. because of increased consumption. This article
      discusses irrational prescribing and the implications for practice.

PMID- 15727019
TI  - Team esteem.

PMID- 15727020
TI  - [Point prevalence of psychoactive substance use and depression in childhood and
      adolescence].
AB  - Increasing use of psychoactive substances and early age of initiation to them
      demand effective methods of prevention and early intervention. In epidemiological
      studies, 12, 15 and 19 years old students responded anonymously to the question
      of BDI and Substance Use Questionnaire. The analysis of 3446 sets of
      questionnaires revealed statistically significant coincidence of depression and
      use of alcohol and "narcotics" in girls and boys in all studied age groups and of
      depression and smoking in 12 y.o. boys. The findings allow for indication of
      depressive children and adolescents as a risk group of substance abuse and
      dependency development.

PMID- 15727021
TI  - [A study on parent-children relations in families with adolescent patients who
      present with different symptomathology].
AB  - The first part of the article deals with the description of the dynamics of
      children-parents relations that influence human development and the process of
      arising mental disturbances. In the second part, the author presents one of the
      research projects on the parents-children relationship in families of adolescent
      patients hospitalised due to various psychiatric diagnoses. The analysis of
      obtained data confirmed research hypothesis about differences in family dynamics
      between groups of families of psychotic adolescent and non-psychotic ones.

PMID- 15727022
TI  - [Psychological characteristics of children and adolescents with primary
      headache].
AB  - THE AIM OF THE WORK: Primary headache involved almost one half of the population
      in developmental age. This ailment still increased. Authors likes to determined
      endogenous and environmental factors of resulting headache in children and
      adolescents. MATERIAL AND METHODS: The group of 78 children and adolescents, 49
      girls and 29 boys, aged 6-17 years, with primary headaches were analysed. 28 of
      them suffered from migraine, 43 from tension headaches and 7 from from of these
      types of headaches. WISC-R and WAIS-R, Bender-Koppitz and Benton tests and
      questionaires "who are you", ISCL-STAI and projections, discussion with children
      and their parents were used. Statistical analysis was done with Fisher,
      variations and a posteriori Scheffe tests. RESULTS: In almost all patients IQ was
      normal. 16-18% of children in D. Wechsler subtests showed disturbances of the
      memory, visual brightness, spatial, visuo-motor organisation. Subtests data were
      higher in children with migraine. In 22-30% of children with primary headaches
      intellectual development was disharmonic. In 13-21% of analysed children
      disturbances were present of the development visuo-motor integretion, visual
      memory, and specific school abilities. Emotional status in children with
      headaches was also disturbed. Migraineurs were rarer repressed, negative emotion
      and were more often self-confident. Majority of children had school problems,
      which was relevant to discrepancy between the level of aspirations and
      achievements. Moreover. children with tension headaches had more often real
      problems with school obligations. Almost one half of the children had family
      problems. CONCLUSION: Tension-type headache were more frequent in children above
      12 years of age. Majority of children and adolescents with primary headache were
      intellectually normal, but IQ and subtest data were higher in the migrainieurs.
      Partial cognitive deficits could be risk factors for headache, particulary
      tension-type headache. Majority of children with primary headache had school
      problems and almost one half of them had family problems.

PMID- 15727023
TI  - [Verbal and drawing expression of primary headaches in developmental age].
AB  - THE AIM OF THE STUDY: Children and adolescents are the subject, which suffers
      from primary headaches. Type and character of the pain is known only by them and
      their relations are necessary to know it. This study was performed to establish
      how children and adolescents express verbally and by paintings their headaches.
      MATERIAL AND METHODS: The group of 52 patients with primary headaches and normal
      IQ was analysed. It was 35 girls and 17 boys, aged 6-17 years. Due to IHS
      International Classification, 20 of them suffered from migraine, and 32 from
      tension headaches. All patients were asked by physician to illustrate their
      headache verbally and by painting. Description should involve details about pain
      character, its localisation, severity, time of duration, frequency and time of
      appearance, and also accompaning symptoms. Instruction was to use 1/2 -1 page and
      to colour paintings. RESULTS: Only 11/52 children illustrated headaches by
      painting. Red colour dominated on these illustrations. 20% of children only
      described pain using verbal expression as normal for their age level. Other
      children used very short elaboration, from laconic to full pain characteristic.
      CONCLUSION: Patients in developmental age more often used verbal than drawing
      expression of their headaches. Migraine and tension headaches drawing was
      significantly different. Also verbal expression of migraine was different in
      localisation and symptoms during pain and accompanied pain. It is necessary to
      investigate headaches in a subjective and quantitative way.

PMID- 15727024
TI  - [Endogenous potentials evoked by acoustic stimulus in children with idiopathic
      headache--preliminary report].
AB  - PURPOSE: Endogenous evoked potentials (P300) are elicited by several stimuli, and
      are electrophysiological consequence of cognitive processing. Abnormalities have
      often been reported in dementive syndromes, demyelinating diseases, metabolic
      disorders, CNS tumors, phacomatoses, neuroinfections, attention deficit
      hyperactivity disorder and epilepsy. The role of this element of
      neurophysiological characteristics is debated in migraine, pato-genetically
      undefined, and other primary headaches. THE AIM: The aim of this research was to
      determine whether the parameters of endogenous responses to the transient
      auditory stimulation in children with migraine differ from parameters obtained
      from children with tension-type headache, and whether the results are different
      in children with primary headaches compared with headache-free controls. SUBJECTS
      AND METHODS: 56 patients, 27 girls and 29 boys aged from 10 to 18 years,
      recruited from the Department of Pediatric Neurology and Headache Outpatient
      Clinic of University Children's Hospital of Cracow were studied between 1.04.2004
      and 31.08.2004. 21 children affected with migraine, 17 with aura, 4 without aura,
      and 15 children with frequent episodic tension-type headache (ETTH) were
      diagnosed according to IHS criteria, and compared with 20 sex- and age-matched
      headache-free controls. Endogenous evoked potentials P300 were performed in all
      children using auditory oddball paradigm, averaging 60 responses to stimuli
      different from the background activity. Responses were recorded using superficial
      electrodes placed on the frontal (Fz), middle (Cz) and parietal (Pz) region,
      while reference electrodes on the ear lobes. The procedure of average out of
      target and non target stimuli was repeated three times in each patient. RESULTS:
      The parameters of latency and amplitude of P300 were not significantly different
      between children with migraine, without aura and ETTH, and healthy controls. On
      the contrary, the amplitude of responses was lower in children with ETTH than in
      controls. However the latency was shortened in children with migraine compared
      with children with other primary headaches and with headache-free controls. There
      was no significant correlation between parameters. CONCLUSION: The findings of
      shortened latency of P300 potentials in children with migraine, esp. migraine
      with aura may contribute to migraine pathogenesis. There were no significant
      differences in the latency and amplitude of P300 potentials in children with
      migraine without aura compared with the frequent ETTH. This finding does not add
      further information to the differentiation of both types of primary headaches.

PMID- 15727025
TI  - [Placebo test in the diagnostics of pseudoepileptic seizures in children and
      adolescents].
AB  - THE AIM OF THE STUDY: The psychogenic pseudoepileptic seizures can be provoked by
      suggestion and by placebo test. This is the possibility that differentiates them
      with epileptic seizures, if there is a chance to record with video EEG. In the
      developmental age the intravenous placebo tests are willingly used, moreover the
      oral placebo has probably the same effectiveness. The Aim of the study was to
      determined the effectiveness of oral placebo in provoking psychogenic paroxysm
      and bioelectrical brain disorders in children with pseudoepileptic seizures. We
      also evaluated the effectiveness of placebo in provoking epileptic seizures in
      children with coexisting epilepsy. MATERIAL: The placebo was given to 30 among 40
      children with pseudoseizures which was diagnosed with video EEG. There were 36
      girls and 4 boys aged 8 to 18 years (average 13 years) hospitalised in the
      Department of Neurology in Krakow between 2002-2004. The most frequent type of
      paroxysm were syncope which needed to be diagnosed, fainting, headache,
      dizziness, paroxysmal abdominal pain and visual disorders. In 15/40 children with
      paroxysmal nonepileptic events the epileptic seizures were coexisting. METHODS:
      Pseudoepileptic seizures were provoked even by the video EEG monitoring,
      suggestion, hyperventilation and placebo probe. For deepening the assessment of
      the EEG pattern beside the hyperventilation reactions test of open and closed eye
      and photostimmulation were used. During the placebo probe video EEG was done with
      voice recording and analyses of the synchrony of clinic and EEG pattern. RESULTS:
      Among 30 children with pseudoepileptic seizures after placebo in 20 paroxysm
      during recording were observed. The character of the paroxysm was similar to the
      previous history. More frequently were observed behavioural and visual disorders
      and rare syncope. No epileptic seizures were developed by placebo. 19/30 children
      with clinically positive and negative placebo test, developed paroxysmal
      bioelectric activity. CONCLUSION: The oral placebo test was clinically effective
      in diagnosis of the pseudoepileptic events in 2/3 children. It developed
      paroxysmal EEG pattern in children with clinically positive and also with
      negative placebo test.

PMID- 15727026
TI  - [Bioelectric activity of the brain in children and adolescents with
      pseudoepileptic seizures].
AB  - THE AIM OF THE STUDY: Pseudo-epileptic seizures are a very crucial clinical
      problem in the developmental age and are coexisting with epileptic seizures in
      children. There is no answer to the question if the appearance of pseudoepileptic
      seizures in this age is connected to bioelectric brain function disorders. In
      adults with pseudoepileptic seizures the temporal area disorders are detected.
      MATERIAL: The video EEG was performed in 36 girls and 4 boys aged 8 to 18 years
      (average 13 years). The most frequent types of pseudo seizure were syncope (30%),
      fainting (15%), abdominal pain (10%) and visual disturbances (10%). In 7.5%
      clonic and tonic-clonic seizures and in 2.5 % paroxysmal sense disorders were
      seen. Confusion of place and time and paroxysmal behavioral disorders in 5%. In 3
      cases hyperventilation was observed. In 15/40 with pseudoseizures epilepsy was
      coexisting. METHODS: In all children 1 hour interictal videoEEG monitoring was
      performed. The pattern was done during waking state and all children was
      activated. In 15, the procedure were repeated after sleep deprivation in
      physiological sleep. We analysed the basic activity, reactivity, symmetry and
      synchrony in the EEG patterns, presence of the epileptic-like grapho-elements and
      paroxysmal discharges. In sleep patterns the bioelectrical features, stages,
      epileptic-like and paroxysmal graphoelements are assessed. RESULTS: In 40%
      children with pseudoepileptic seizures, abnormalities of the interictal EEG were
      seen. Sleep deprivation provoked the abnormalities in another 4/15 children. In
      this pattern 27.5% children had localized paroxysmal discharges, and 22.5%
      generalized. In most of the cases the EEG was sensitive to stimulation.
      CONCLUSION: Pseudoepileptic seizures appear mostly in girls. One half of these
      cases had basic EEG pattern and paroxysmal bioelectric abnormalities, however
      12/20 of them had epileptic seizures as well.

PMID- 15727027
TI  - [Assement of clumsiness in children with partial and generalized epilepsy].
AB  - THE AIM OF THE STUDY: Epilepsy in the developmental age is connected in some
      cases with disorders of gross motor dysfunction, but in the others every day
      motor activity is not disturbed. Although it does not mean that in children with
      epilepsy there are not diagnosed any different motor disorders. Aim of the study
      was to determined the differences between epilepsy with and without gross motor
      function disorders, the appearance of clumsiness in children with partial
      epilepsy and primary generalised. MATERIAL: The study was performed on a group of
      40 children with idiopathic epilepsy, 23 with idiopathic partial seizures and 17
      with generalised. In this group boys predominated (14/23 and 11/17). The average
      age of both groups was not significant different (12.5 and 13.4). The assessment
      of gross motor function and intellectual development was normal. METHODS: The
      assessment of clumsiness was performed by using 10 tests classifying 3 categories
      of movement: co-ordination, integration, balance. To diagnose the type of
      epilepsy the common used clinical, electrophisiological and neuroimaging
      procedures were done. The statistic assessment was performed by using T-test for
      independent probe. RESULTS: There were no differences between groups of children
      in 2 test evaluating balance, which were normal. Children with generalised
      epilepsy had normal results in other 5 test. The lower results were observed in
      children with partial epilepsy in 8 and with generalised in 3 tests, but this
      difference was not statistically significant (VAR2/VAR1 = 0.793 and AR3/VAR1 =
      0.965). Results of children with partial seizures were lower in 8 tests, but it
      was not statistically significant(VAR3/ VAR2 = 0.827). The most expressive
      difference was seen in the test of balance with jumping. CONCLUSION: Children
      with partial epilepsy are a little more clumsy than children with primary
      generalised epilepsy.

PMID- 15727028
TI  - [Endogenous anticonvulsant and neuroprotective agents].
AB  - Elucidation of the biochemical basis of neuronal degeneration following seizures,
      ischemia or hypoglycemia appears to be one of the most urgent problems of
      contemporary science. Close attention has been devoted to endogenous
      anticonvulsant and/or neuroprotective agents which help to maintain a neuronal
      homeostasis under pathological conditions. The list of putative neuroprotectants
      is very long and includes substances with diverse chemical structures, such as,
      e.g., adenosine, amino acids (kinurenic acid, taurine), neuropeptides (opioid
      peptides, thyreoliberine, neuropeptide Y, galanin, VIP/PACAP) and some
      neurosteroids (allopregnanolone, dehydroepiandrosterone). In recent years great
      progress has been made in the studies into not only their biosynthesis,
      metabolism and regulation of release in the nervous tissue, but also molecular
      and functional characteristics of their receptors. Apart from fast ionic effects
      leading to repolarization of the neuronal membrane, these endogenous
      neuroprotective agents may exert long-term effects on intracellular second
      messengers and genomic mechanisms which are crucially involved in the regulation
      of excitotoxic and apoptotic cascades. It is still an open question whether in
      the foreseeable future the presented direction of research will allow us to
      regulate endogenous anticonvulsant and neuroprotective mechanisms in a subtle way
      in order to substitute for or support other forms of treatment.

PMID- 15727029
TI  - [Neuroprotective activity of antiepileptic drugs].
AB  - Clinical and experimental data indicate that epilepsy may lead to neuronal death
      and lesions placed in diverse brain regions. Also, the anticonvulsant activity of
      some antiepileptic drugs can be impaired in case of neurodegeneration in the
      brain. The main aim of this review is making a reader familiar with a
      patomechanism of neurodegeneration as well as the current data concerning the
      neuro-protective potential of antiepileptic drugs. It is noteworthy that a great
      number of papers devoted to this problem concern animal models of
      neurodegeneration produced by either seizure activity or ischemia. Interestingly,
      there are apparent differences in the direct central effects of antiepileptic
      drugs in adult and young animals. Majority of antiepileptics at anticonvulsant
      doses produce massive apoptosis in brains of young rodents, this effect being not
      present in adult animals. Only topiramate required higher than anticonvulsant
      doses to induce apoptotic response. Neuroprotective activity in models of
      ischemia and epilepsy was evident for benzodiazepines (diazepam), lamotrigine,
      tiagabine, topiramate, and vigabatrin. Recently, topiramate has been documented
      to exert potent neuroprotective action in human oligodendrocytes exposed to
      hypoxic-ischemic damage.

PMID- 15727030
TI  - [Attachment and brain development].
AB  - Significant achievements of neuroscience point out a role of stimulation in
      infant brain development. Attachment style is found to reflect in development of
      cortex--limbic system functional structures having this way fundamental influence
      on emotional development of the child and its future mental health. Styles of
      attachment are in this way transmitted from generation to generation. Before
      treatment methods based on these finding will be developed, prevention in a form
      of infant care and psychotherapy should be introduced.

PMID- 15727031
TI  - [Revealing new contexts of violence in therapeutic work with families (from label
      to description)].
AB  - The authors present numerous contexts which create and support the phenomenon of
      violence. They describe family psychotherapy as a tool which reveals a variety of
      factors in the ethology and creation of aggressive behaviors. They also present
      the possibilities and limitations of family therapy as a method of changing
      violent behaviors in and outside family.

PMID- 15727032
TI  - [Hyperkinetic disorder--etiology, diagnosis, therapy, doubts].
AB  - Hyperkinetic Disorder is the most common psychiatric condition diagnosed in
      children. It is also the most controversial one and gives rise to extreme
      differences of opinions. Hipercinetic Disorder is viewed as a stigmatizing and
      harmful label attached to children who are difficult to handle. The opponents
      indicate the source of popularity of the syndrome in the crisis educational
      system and the marketing activity of pharmaceutical companies. According to
      supporters, the lack of diagnosis and treatment of Hyperkinetic Disorder may
      produce serious, life devastating emotional and social dysfunctions in suffering
      from the condition children. Most probably the Hyperactivity subject will became
      more and more popular in our country in the future, especially because two drugs
      prescribed in this condition are now in the process of registration in Poland.
      The article is an attempt to make a critical analysis of the current scientific
      knowledge on prevalence, diagnosis, etiology and therapeutic schemes of
      Hyperkinetic Disorder.

PMID- 15727033
TI  - [Family loyalty problems and anorexia nervosa].
AB  - In this article discuses basic pre-suppositions of the Ivan Boszormenyi-Nagy's
      conception of invisible loyalties and makes general characteristic of anorexia
      nervosa with attention to family and personal (individualistic) etiological
      trouble elements. Based on therapeutic experience during the work with anorexia
      patients and their families, it is becoming an expanded presupposition that one
      of the fundamental reasons of protruding anorexia nervosa is family loyality
      problems, children's loyality conflicts and troubles with the give-and-take
      process.

PMID- 15727034
TI  - [Family factors as risk factors and perpetuating mechanisms in anorexia and
      bulimia nervosa].
AB  - In recent years more and more attention in studies on eating disorders is paid to
      risk factors and perpetuating mechanisms present in the disorders. Perpetuating
      mechanisms, most often of intricate character, influence patients' ambivalent
      attitude to therapy. Recognition of the perpetuating mechanisms, often connected
      with the patients' family way of functioning, makes the therapy much easier.
      Essential risk factors and perpetuating mechanisms are discussed.

PMID- 15727035
TI  - [Characteristic of social phobia in adolescents].
AB  - In this review, issues concerning epidemiology, etiology, diagnostic criteria and
      treatment of social phobia are presented. This disorder is one of the most common
      anxiety disorders in adolescents. The main symptom of the disorder is a fear of
      possible scrutiny by others in the social situation and, as a consequence,
      avoiding such situations. Data from recent studies suggest that lifetime
      prevalence rates of social phobia in adolescent are several and up to anywhere
      from ten to, or even over twenty per cent. There is a high comorbidity of social
      phobia and other psychiatric disorders in youth, it is often seen in adolescents
      who refuse to go to school. Social phobia is often underestimated. In case of
      severity of the disorder that interferes with daily functioning adequate
      psychotherapy is needed. The main aim of treatment of social phobia in youth is
      improvement of their quality of life.

PMID- 15727036
TI  - Species-energy relationships at the macroecological scale: a review of the
      mechanisms.
AB  - Correlations between the amount of energy received by an assemblage and the
      number of species that it contains are very general, and at the macro-scale such
      species-energy relationships typically follow a monotonically increasing curve.
      Whilst the ecological literature contains frequent reports of such relationships,
      debate on their causal mechanisms is limited and typically focuses on the role of
      energy availability in controlling the number of individuals in an assemblage.
      Assemblages from high-energy areas may contain more individuals enabling species
      to maintain larger, more viable populations, whose lower extinction risk elevates
      species richness. Other mechanisms have, however, also been suggested. Here we
      identify and clarify nine principal mechanisms that may generate positive species
      energy relationships at the macro-scale. We critically assess their assumptions
      and applicability over a range of spatial scales, derive predictions for each and
      assess the evidence that supports or refutes them. Our synthesis demonstrates
      that all mechanisms share at least one of their predictions with an alternative
      mechanism. Some previous studies of species-energy relationships appear not to
      have recognised the extent of shared predictions, and this may detract from their
      contribution to the debate on causal mechanisms. The combination of predictions
      and assumptions made by each mechanism is, however, unique, suggesting that, in
      principle, conclusive tests are possible. Sufficient testing of all mechanisms
      has yet to be conducted, and no single mechanism currently has unequivocal
      support. Each may contribute to species-energy relationships in some
      circumstances, but some mechanisms are unlikely to act simultaneously. Moreover,
      a limited number appear particularly likely to contribute frequently to species
      energy relationships at the macro-scale. The increased population size, niche
      position and diversification rate mechanisms are particularly noteworthy in this
      context.

PMID- 15727037
TI  - Revealing metabolic phenotypes in plants: inputs from NMR analysis.
AB  - Assessing the performance of the plant metabolic network, with its varied
      biosynthetic capacity and its characteristic subcellular compartmentation,
      remains a considerable challenge. The complexity of the network is such that it
      is not yet possible to build large-scale predictive models of the fluxes it
      supports, whether on the basis of genomic and gene expression analysis or on the
      basis of more traditional measurements of metabolites and their interconversions.
      This limits the agronomic and biotechnological exploitation of plant metabolism,
      and it undermines the important objective of establishing a rational metabolic
      engineering strategy. Metabolic analysis is central to removing this obstacle and
      currently there is particular interest in harnessing high-throughput and/or large
      scale analyses to the task of defining metabolic phenotypes. Nuclear magnetic
      resonance (NMR) spectroscopy contributes to this objective by providing a
      versatile suite of analytical techniques for the detection of metabolites and the
      fluxes between them. The principles that underpin the analysis of plant
      metabolism by NMR are described, including a discussion of the measurement
      options for the detection of metabolites in vivo and in vitro, and a description
      of the stable isotope labelling experiments that provide the basis for metabolic
      flux analysis. Despite a relatively low sensitivity, NMR is suitable for high
      throughput system-wide analyses of the metabolome, providing methods for both
      metabolite fingerprinting and metabolite profiling, and in these areas NMR can
      contribute to the definition of plant metabolic phenotypes that are based on
      metabolic composition. NMR can also be used to investigate the operation of plant
      metabolic networks. Labelling experiments provide information on the operation of
      specific pathways within the network, and the quantitative analysis of steady
      state labelling experiments leads to the definition of large-scale flux maps for
      heterotrophic carbon metabolism. These maps define multiple unidirectional fluxes
      between branch-points in the metabolic network, highlighting the existence of
      substrate cycles and discriminating in favourable cases between fluxes in the
      cytosol and plastid. Flux maps can be used to define a functionally relevant
      metabolic phenotype and the extensive application of such maps in microbial
      systems suggests that they could have important applications in characterising
      the genotypes produced by plant genetic engineering.

PMID- 15727038
TI  - Biological invasions in the Antarctic: extent, impacts and implications.
AB  - Alien microbes, fungi, plants and animals occur on most of the sub-Antarctic
      islands and some parts of the Antarctic continent. These have arrived over
      approximately the last two centuries, coincident with human activity in the
      region. Introduction routes have varied, but are largely associated with movement
      of people and cargo in connection with industrial, national scientific program
      and tourist operations. The large majority of aliens are European in origin. They
      have both direct and indirect impacts on the functioning of species-poor
      Antarctic ecosystems, in particular including substantial loss of local
      biodiversity and changes to ecosystem processes. With rapid climate change
      occurring in some parts of Antarctica, elevated numbers of introductions and
      enhanced success of colonization by aliens are likely, with consequent increases
      in impacts on ecosystems. Mitigation measures that will substantially reduce the
      risk of introductions to Antarctica and the sub-Antarctic must focus on reducing
      propagule loads on humans, and their food, cargo, and transport vessels.

PMID- 15727039
TI  - Is more choice always desirable? Evidence and arguments from leks, food
      selection, and environmental enrichment.
AB  - Recent studies on humans show that too much choice can make subjects less likely
      to choose any item. I consider general adaptive and non-adaptive explanations of
      why such choice aversion, or its converse, might occur in animals. There are
      three questions: is more choice always preferred, does it ever lead to less
      consumption (or a lower probability of consumption), and may it result in worse
      items being selected ? A preference for choice is one of the main explanations
      for lek formation and I draw attention to previously unrecognised parallels with
      models of human shopping behaviour. There is indeed evidence of female preference
      for larger leks, although much of the observational data are open to other
      interpretations. Unfortunately nobody has looked for choice aversion where it is
      most to be expected, in leks larger than normally occur. Evidence that too much
      choice of males confuses females is strongest in acoustically advertising frogs,
      but the widespread decrease of mating skew in larger leks might also have this
      explanation. A model reanalyses data on skew in black grouse Tetrao tetrix and
      suggests that considering only a random subset of a large lek may increase the
      chances of selecting the better males: larger leks are more likely to include
      better males, but these are less likely to be selected. These opposing effects
      may lead to an optimum lek size, but only with a sufficient decline in choice
      accuracy with size. With food choice, very few studies have avoided confounding
      choice with food quality, by manipulating only flavour. The widespread phenomena
      of stimulus-specific satiety and novelty seeking imply that monotonous diets are
      aversive, but no studies test whether animals choose sites where they know food
      diversity to be greater. Operant experiments that demonstrate mild preferences
      for free choice concern choice about the means to get food rather than the food
      itself. In some insect species even moderate choice of diet can be deleterious,
      and studies on search images and the confusion effect may be evidence of this in
      vertebrates. Environmental enrichment of captive animals often relies on
      increasing the options available, but it need not be the choice itself that is
      beneficial. I consider briefly further areas in biology where choice preference
      or aversion are potentially important.

PMID- 15727040
TI  - Phylogeny and life histories of the 'Insectivora': controversies and
      consequences.
AB  - The evolutionary relationships of the eutherian order Insectivora (Lipotyphla
      sensu stricto) are the subject of considerable debate. The difficulties in
      establishing insectivore phylogeny stem from their lack of many shared derived
      characteristics. The grouping is therefore something of a 'wastebasket' taxon.
      Most of the older estimates of phylogeny, based on morphological evidence,
      assumed insectivore monophyly. More recently, molecular phylogenies argue
      strongly against monophyly, although they differ in the extent of polyphyly
      inferred for the order. I review the history of insectivore phylogenetics and
      systematics, focussing on the relationships between the six extant families
      (Erinaceidae--hedgehogs and moonrats, Talpidae - moles and desmans, Soricidae -
      shrews, Solenodontidae--solenodons, Tenrecidae--tenrecs and otter-shrews and
      Chrysochloridae--golden moles). I then examine how these various phylogenetic
      hypotheses influence the results of comparative analyses and our interpretation
      of insectivore life-history evolution. I assess which particular controversies
      have the greatest effect on results, and discuss the implications for comparative
      analyses where the phylogeny is controversial. I also explore and suggest
      explanations for certain insectivore life-history trends: increased gestation
      length and litter size in tenrecs, increased encephalization in moles, and the
      mixed fast and slow life-history strategies in solenodons. Finally, I consider
      the implications for comparative analyses of the recent strongly supported
      phylogenetic hypothesis of an endemic African clade of mammals that includes the
      insectivore families of tenrecs and golden moles.

PMID- 15727041
TI  - Parasite plastids: approaching the endgame.
AB  - Considerable work still needs to be done to understand more fully the basic
      processes going on inside the non-photosynthetic plastid organelle of Plasmodium
      spp., the causative agent of malaria. Following an explosion of genomic and
      transcriptional information in recent years, research workers are still analysing
      these data looking for new material relevant to the plastid. Several metabolic
      and housekeeping functions based on bacterial biochemistry have been elucidated
      and this has given impetus to finding lead inhibitors based on established anti
      microbials. Structural investigations of plastid-associated enzymes identified as
      potential targets have begun. This review gives a perspective on the research to
      date and hopes to emphasize that a practical outcome for the clinic should be an
      important focus of future efforts. Malaria parasites have become resistant to
      front-line anti-malarials that are widely used and were formerly dependable. This
      has become a worrying problem in many regions where malaria is endemic. The time
      lag between hunting for new inhibitors and their application as pharmaceuticals
      is so long and costly that a steady stream of new ventures has to be undertaken
      to give a reasonable chance of finding affordable and appropriate anti-malarials
      for the future. Attempts to find inhibitors of the plastid organelle of the
      malaria parasite should be intensified in such programmes.

PMID- 15727043
TI  - Occupational science: bridging occupation and health.
AB  - BACKGROUND: The paper is based on a keynote address delivered at the 2004 CAOT
      Conference in Charlottetown, Prince Edward Island Occupational therapists are
      widely associated with a medical model of health care in which recognition of how
      engagement in occupation contributes to health status is poorly understood.
      Occupational science as the study of people as occupational beings has the
      potential to increase such understanding. PURPOSE: This paper considers some
      aspects of the relationship between health and the occupations of older people to
      highlight avenues for change and the research required to support them. METHOD:
      The paper is structured around a simple verse of dialogue between a healthy old
      man and an occupational therapist. Explanation of the dialogue draws upon
      historical and current literature as well as occupational science research to
      provide a rationale for future practice based on broader concepts of occupation
      for health. RESULTS AND PRACTICE SUGGESTIONS: The dialogue promotes the need for
      discussion about health and about the health notion of Active Ageing. It
      highlights professional language as one impediment to change and suggests that
      research concerning occupation as it relates to population health is a primary
      requirement for the future of occupational therapy.

PMID- 15727042
TI  - Dietary fats and membrane function: implications for metabolism and disease.
AB  - Lipids play varied and critical roles in metabolism, with function dramatically
      modulated by the individual fatty acid moities in complex lipid entities. In
      particular, the fatty acid composition of membrane lipids greatly influences
      membrane function. Here we consider the role of dietary fatty acid profile on
      membrane composition and, in turn, its impact on prevalent disease clusters of
      the metabolic syndrome and mental illness. Applying the classical physiological
      conformer-regulator paradigm to quantify the influence of dietary fats on
      membrane lipid composition (i.e. where the membrane variable is plotted against
      the same variable in the environment--in this case dietary fats), membrane lipid
      composition appears as a predominantly regulated parameter. Membranes remain
      relatively constant in their saturated (SFA) and monounsaturated (MUFA) fatty
      acid levels over a wide range of dietary variation for these fatty acids.
      Membrane composition was found to be more responsive to n-6 and n-3
      polyunsaturated fatty acid (PUFA) levels in the diet and most sensitive to n-3
      PUFA and to the n-3/n-6 ratio. These differential responses are probably due to
      the fact that both n-6 and n-3 PUFA classes cannot be synthesised de novo by
      higher animals. Diet-induced modifications in membrane lipid composition are
      associated with changes in the rates of membrane-linked cellular processes that
      are major contributors to energy metabolism. For example, in the intrinsic
      activity of fundamental processes such as the Na+/K+ pump and proton pump-leak
      cycle. Equally, dietary lipid profile impacts substantially on diseases of the
      metabolic syndrome with evidence accruing for changes in metabolic rate and
      neuropeptide regulation (thus influencing both sides of the energy balance
      equation), in second messenger generation and in gene expression influencing a
      range of glucose and lipid handling pathways. Finally, there is a growing
      literature relating changes in dietary fatty acid profile to many aspects of
      mental health. The understanding of dietary lipid profile and its influence on
      membrane function in relation to metabolic dysregulation has exciting potential
      for the prevention and treatment of a range of prevalent disease states.

PMID- 15727044
TI  - Facilitating client-centred practice: insights from clients.
AB  - BACKGROUND: This paper adds to the established importance of client-centred
      practice in mental health programs by reporting on the outcome of client
      interviews in one community setting in England. PURPOSE: The purpose of these
      interviews was to determine the opportunities for, and barriers to, the
      application of a definition of client-centred practice. METHODS: Purposive
      sampling was used to obtain 9 clients who participated in structured interviews.
      A combination of methods, including template analysis and the editing approach,
      were employed to determine themes and sub themes that are presented within the
      context of the clients'reasons for attending these programs. RESULTS: These
      themes included initiating client-centred practice with the sub themes of
      providing information to enable choice, participate in negotiating goals,
      overcoming fear and the severity of illness. Other themes related to the
      therapist's response to the client's illness and the client's knowledge about
      client-centred practice. PRACTICE IMPLICATIONS: It was clear from these
      interviews that client-centred practice was important to this group of clients
      and there were both opportunities and barriers to be considered by therapists.

PMID- 15727045
TI  - The influence of virtual reality play on children's motivation.
AB  - PURPOSE: This study explored the degree of motivation children exhibit during
      virtual reality (VR) play sessions. METHOD: Sixteen children with cerebral palsy
      aged 8 to 12 years participated. They were observed during a variety of VR
      environments that were video recorded. The Pediatric Volitional Questionnaire
      (PVQ) was used to measure children's motivation. The PVQ provides insights into
      children's inner motives as well as how the virtual environment enhances or
      attenuates children's motives. Nine VR environments were randomly selected to
      score with the PVQ. RESULTS: Data were analyzed and descriptive statistics were
      calculated for modes and medians of total volition scores for each VR
      environment. Different environments produced varying levels of volitional
      behaviour. The features of environments that produced higher levels of volition
      included challenge, variability and competition. PRACTICE IMPLICATIONS: The
      overall volitional scores of children with cerebral palsy in the current study
      indicate that VR play is a motivating activity and thus has potential as a
      successful intervention tool.

PMID- 15727046
TI  - [Utilization of the Canadian Occupational Performance Measure (COPM) among
      children and their parents: a Swiss experience].
AB  - BACKGROUND: This descriptive and exploratory study examined the use of the
      Canadian Occupational Performance Measure (COPM) involving 33 children and their
      parents in French speaking Switzerland. The overall aim of the study was to
      determine the utility of the measure in order to objectivize the impact of the
      treatment. METHOD: The COPM was administered twice (initial assessment and
      reassessment) in order to measure the change in occupational performance and
      satisfaction over time. The interviews were conducted by 18 occupational
      therapists, either separately or with both the parents and children together.
      RESULTS: The analyses highlight the statistically significant changes that
      occured between the initial assessment and the reassessment, in both the
      occupational performance and satisfaction. It appears that occupational
      therapists plan to use the COPM more as a guide when interviewing the parents and
      the children, rather than as an evaluation tool. Only 17 % of the occupational
      therapists indicated that they intended to use the point rating scale, but the
      majority said that the COPM would be useful in establishing a better partnership
      between parents and professionals. PRACTICE IMPLICATIONS: The contribution of
      this study lies not only in the results of the research confirming the relevance
      of the COPM in measuring the impact of practice, but also in the influence of its
      use on occupational therapy practice, with a greater focus on the needs of the
      clients and on their independance in daily life.

PMID- 15727047
TI  - Exploring recruitment strategies to hire occupational therapists.
AB  - BACKGROUND: Recruitment issues in occupational therapy have been a long-standing
      concern for the profession. PURPOSE: This descriptive study explored the
      strategies currently being used by employers to recruit occupational therapists
      for employment purposes. METHOD: An 18-item survey was mailed to 251 sites where
      occupational therapists work in Alberta and Saskatchewan. RESULTS: There was a
      64% response rate and data from 130 surveys were analyzed. The results indicate
      that employers continue to rely on a wide variety of strategies for advertising
      and recruiting, the most prevalent being word of mouth, postings at universities,
      and providing student fieldwork placements. In turn, the most effective
      recruitment strategies were listed as word of mouth, advertising in the general
      media, and providing student fieldwork placements. Various examples of financial
      incentives offered by employers were also listed. Many participants identified
      recent changes in recruitment strategies such as making a move towards web site
      job postings. PRACTICE IMPLICATIONS. The results suggest strategies for employers
      to target for recruiting occupational therapists and illustrate to both employers
      and students the importance of fieldwork in recruitment and hiring.

PMID- 15727048
TI  - [Theories of behavior change through preventive and health promotion
      interventions in occupational therapy].
AB  - BACKGROUND: Community occupational therapy practice challenges therapists in
      their health educator role and incites them to implement preventive strategies
      with their clients. Working in the community also provides an interesting context
      for the implementation of strategies targeting health promotion at the community
      level. PURPOSE: This article describes some of the theories that are used in the
      public health and health promotion fields to explain health-related behaviour
      change. It also highlights their potential for community practice in occupational
      therapy. The theories presented in this paper are the health belief model, social
      cognitive theory, theory of reasoned action and theory of planned behavior. They
      are among the most widely used for health-related behaviour analysis and
      intervention. PRACTICE IMPLICATIONS: Since these theories emphasize a set of
      factors that influence health behaviours, reviewing these theories could
      contribute to enhance the effectiveness of educational interventions with regards
      to clients'adherence to their prevention and health promotion recommendations.

PMID- 15727049
TI  - Dispelling the disability stereotype: embracing a universalistic perspective of
      disablement.
AB  - BACKGROUND: The notion of universalism was introduced to me during my first year
      of PhD studies in Rehabilitation Science. During a class discussion, we debated
      the merits of two theoretical perspectives that offered contradicting views as to
      the most effective means to facilitating a shift in societal perceptions of
      disability. As exemplified by the World Health Organization's current model of
      health, the International Classification of Functioning, Disability and Health
      (ICF), there has been a shift from a minority group analysis towards a
      universalistic perspective of disablement. PURPOSE: This paper introduces readers
      to the underlying concepts of both minority group analysis and universalism and,
      in doing so, proposes that universalism is closely aligned with the underlying
      constructs of occupational therapy. Universalism provides a comprehensive
      framework that can be utilized by occupational therapists to encourage the
      development of health and social-related policies that promote inclusiveness, yet
      still the respect the differences that exist among individuals. PRACTICE
      IMPLICATIONS By improving their familiarity with such theories, occupational
      therapists may be better positioned to contribute to policy development within
      their respective treatment and/or community settings.

PMID- 15727051
TI  - Hydroxyl radical formation resulting from the interaction of nickel complexes of
      L-histidine, glutathione or L-cysteine and hydrogen peroxide.
AB  - L-histidine, L-cysteine, reduced glutathione (GSH) and other bioligands, which
      are ubiquitously present in biological systems, are recognized as antioxidants.
      Studies have shown that nickel (II) complexed with these ligands catalyzes the
      disproportionation of H2O2, leading to the generation of hydroxyl radicals (OH
      radical). However, none of the studies could provide information regarding
      effective concentrations at which these ligands act either as pro-oxidant or
      antioxidant. Therefore, the observed paradoxical behaviour of biological
      antioxidants in nickel-induced oxidative response was evaluated. Benzoic acid
      (BA) is hydroxylated by OH radical to form highly fluorescent dihydroxy benzoate
      (OH-BA). We used this model to study the effect of nickel complexes of L
      histidine, GSH or L-cysteine on the hydroxylation of BA. The concentration
      dependent effect of L-histidine, GSH and L-cysteine, or nickel on the
      hydroxylation of BA was studied. The hydroxylation of BA was significantly
      enhanced up to 1:0.5 molar ratio (Ni:hist or GSH). However, beyond 1:0.5 molar
      ratios, histidine/GSH inhibited the hydroxylation and complete inhibition was
      observed at 1:1 molar ratios. Sorbitol and caffeic acid, considered as scavengers
      of hydroxyl radicals, inhibited nickel-induced hydroxylation of BA. The present
      study demonstrates paradoxical behaviour of these bioligands. They act as pro
      oxidant at lower ligand ratios and as antioxidant at higher ligand ratios. The
      redox properties of nickel complexes with histidine, GSH or cysteine reported
      here may be crucial for the toxicity of nickel.

PMID- 15727050
TI  - Recent advances in understanding transforming growth factor beta regulation of
      orofacial development.
AB  - Members of the transforming growth factor (TGF) family have emerged as critical
      contributors to the choreography of cellular and tissue interactions underlying
      morphogenesis of the orofacial region. The TGFs beta, and their downstream
      effector molecules, the Smads, play a pivotal role in normal as well as abnormal
      development of first branchial arch structures. Components of the TGFbeta signal
      transduction machinery are discussed in relation to regulation of transcription,
      cell division and tissue differentiation in developing orofacial tissue, as
      evidence for a functional linkage between the TGFbeta and retinoic acid signal
      transduction pathways during orofacial development.

PMID- 15727052
TI  - Electrophysiological safety of DW-286a, a novel fluoroquinolone antibiotic agent.
AB  - Inhibition of the potassium current I(Kr) and QT prolongation has been known to
      be associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden
      cardiac death. We investigated the cardiac electrophysiological effects of DW
      286a, a new class of fluoroquinolone antibiotics reported to prolong the QT
      interval. To investigate the electrophysiological safety of DW-286a, we used
      conventional microelectrode recording techniques in isolated guinea pig papillary
      muscles, whole-cell patch clamp techniques in human ether-a-go-go related gene
      (hERG)-transient transfected Chinese hamster ovary cells, and in vivo
      electrocardiogram (ECG) measurements in Sprague-Dawley (SD) rats by the use of a
      telemetry system. DW-286a at 300 microM significantly (P<0.01) prolonged action
      potentials at 50% repolarization (APD50) and 90% repolarization (APD90). For
      IHERG, the IC50 value was 89.00+/-37.85 microM with a Hill coefficient (nH) of 
      0.97+/-0.49. However, when DW-286a was orally administered to conscious SD rats
      at a high dose (1000 mg/kg), no significant effect on ECG in vivo was detected.
      From a previous study, we know that concentration at 19.8 microM is the
      antimicrobial end-point of DW-286a. Therefore, our data suggest that in the
      electrophysiological aspect, it can be thought that the effective concentrations
      of DW-286a are between 19.8 and 100 microM (concentration in serum).

PMID- 15727053
TI  - Occupational exposure to aluminium phosphide and phosphine gas? A suspected case
      report and review of the literature.
AB  - The manufacture and application of aluminium phosphide fumigants pose risks of
      inhalation exposure to phosphine gas. This article presents a case report of
      suspected inhalation exposure to phosphine gas in a manufacturing facility for
      aluminium phosphide fumigants, which was associated with acute dyspnoea,
      hypotension, bradycardia and other signs of intoxication. These symptoms resolved
      within several hours after removal from exposure. A review of the data on human
      exposures to phosphide fumigants identifies both pesticide applicators and
      individuals in the vicinity of application to be at risk of accidental exposure
      and injury from phosphine inhalation. More recent reports have identified risks
      of phosphine gas inhalation in association with the clandestine production of
      methamphetamine. Toxicodynamic effects of phosphine result from the inhibition of
      cytochrome c oxidase and subsequent generation of reactive oxygen species. There
      remain unanswered questions relating to the toxicokinetics of phosphine, as well
      as the assessment of human exposure utilizing biomarkers. As initial signs and
      symptoms of intoxication from phosphine gas may be nonspecific and transient,
      there is a need for improved recognition of the potential hazards associated with
      phosphide fumigants and phosphine gas.

PMID- 15727054
TI  - Toxicogenomics: regulatory perspective on current position.
AB  - Published studies on the utility of toxicogenomic approaches (transcriptomics,
      proteomics and metabonomics) in screening for toxicological mechanisms and
      evaluation of dose response effects have been reviewed. The information supports
      the use of transcriptomics to screen for specific toxicological mechanisms for
      which there is an a priori hypothesis, although in some areas such as
      mutagenicity testing, toxicogenomics appear to have limited value for identifying
      mutagens. Data from such screening approaches cannot be used to exclude the
      possibility of toxicity. Targeted transcriptomics might be valuable for screening
      for specific mechanisms of toxicity considered to be irrelevant for assessing
      risk to humans, which would help to reduce the need for detailed testing of some
      chemicals. An integrated approach is suggested where data from more than one
      toxicogenomic approach could be used as an adjunct to conventional toxicology to
      assess dose-response in toxicological tests. An outline preliminary proposal for
      use by regulators is suggested although it is noted that more data are required
      before this could be formally used in a decision-making process.

PMID- 15727055
TI  - The search for magic solutions.

PMID- 15727056
TI  - Appreciating diversity through stories about the lives of deaf people of color.
AB  - One way of enhancing appreciation of cultural diversity within the American Deaf
      community is by collecting and analyzing stories about Deaf people of color. The
      authors examined biographical profiles in national print and visual media
      published since 1988. The materials focused on life stories of individuals
      identified as Deaf persons of color (e.g., Deaf and identified as Black/African
      American, Hispanic/Latino, Asian/Pacific Islander, or American Indian/Alaskan
      Native). Anecdotes were selected that provided a sociocultural rather than
      medical or pathological perspective and reflected the featured individual's
      viewpoint. Four categories of shared experiences emerged: experiences related to
      overcoming obstacles to educational opportunities, stories about individuals who
      influenced the direction the featured individual took in life, childhood and
      family experiences, and experiences relating to stereotypes, cultural conflicts,
      or discrimination. The authors conclude by discussing lessons and messages
      derived from the stories.

PMID- 15727057
TI  - What do we know about deaf clients after thirteen years of ambulatory mental
      health care? An analysis of the PsyDon database, 1987-1999.
AB  - Little is known about demographic, deafness-related, and diagnostic
      characteristics of deaf and partially hearing people with psychosocial or
      psychiatric problems. A study was conducted derived from data from intake
      assessment interviews of people with hearing loss treated at a Dutch ambulatory
      mental health center for the deaf between 1987 and 1999. Both sexes were equally
      represented. People who were postlingually deaf, hard of hearing, below age 22
      years, or above age 65 years were less likely to ask for help than other groups
      in the study. Men presented more psychiatric disorders, and women more
      psychosocial problems, especially partially hearing women. The authors recommend
      stronger emphasis on mental health care for postlingually deaf people, severely
      hard of hearing people, adolescents, and retirement-age people. They also
      recommend development of skills for rational and emotional self-expression in the
      education and rearing of children with hearing loss.

PMID- 15727058
TI  - Effectiveness of multimedia reading materials when used with children who are
      deaf.
AB  - The purpose of the study was to assess the relative effectiveness of print, sign,
      and pictures in the transfer of reading-related information to children who are
      deaf. By means of personal computers, deaf children were presented CD-ROM
      generated stories in four different formats: print only, print plus pictures,
      print plus sign language, and print plus pictures plus sign. A repeated-measure
      design was used to analyze participants' reading comprehension performance.
      Significant differences were found among the four presentation options. One
      observed phenomenon was that participants would switch from American Sign
      Language to Signed English when analyzing text. The study findings suggest that
      presenting stories on CD-ROM with multiple modes of reading cues, such as print,
      pictures, and sign language, may be an enjoyable and interesting supplement to
      standard reading practices.

PMID- 15727059
TI  - Deaf and hearing individuals' beliefs about the capabilities of deaf people.
AB  - The study explored the beliefs of 100 residents of Greece about the capabilities
      of deaf people living in that country. Participants included deaf adults who
      communicated in Greek Sign Language (GSL), deaf adults who communicated orally,
      hearing adults who attended GSL courses, and hearing adults who did not attend
      such courses. Beliefs were explored through the ODP (Opinions About Deaf People)
      scale (Berkay, Gardner, & Smith, 1995) and an open-ended interview. All
      participant groups viewed deaf people's capabilities positively, but Deaf users
      of GSL expressed the most positive beliefs. The findings suggest that less
      positive beliefs reflect diverse ideological views toward GSL and Deaf culture or
      an awareness of the obstacles preventing deaf people from developing their
      potential. The Deaf community's role in empowering deaf people and the role of
      GSL courses in promoting awareness regarding deaf people are also discussed.

PMID- 15727060
TI  - Marital status and birthrate of deaf people in two Swedish counties: the impact
      of social environment in terms of deaf community.
AB  - Deafness affects many social interactions. The impact of deafness depends on
      several factors, e.g., the type of social environment in terms of the particular
      Deaf community a person lives in. The authors recorded the birthrate and the
      proportions of married and divorced people among deaf people in two Swedish
      counties: Narke, which had a strong Deaf community, and Varmland, whose Deaf
      community was weak. In both counties, the authors found that deafness was
      associated with low marriage rates and low birthrates. Further, in Narke, 99% of
      the people in the sample were married to another deaf person; only 10% were in
      Varmland. In Narke, the divorce rate among deaf people was about the same as that
      of the reference population (i.e., the county's marriage-age population). In
      Varmland, deaf people had a relatively low divorce rate. The findings are
      discussed from medical and social perspectives.

PMID- 15727061
TI  - Visual performance of adults with prelingual auditory impairment.
AB  - Reaction times and picture evaluations by 18 adults with hearing loss were
      compared with those of 18 matched controls during two visual priming tasks. In
      Task 1, participants reacted to sexual and plant target pictures (while
      influenced by similar preceding pictures) by pressing "sex" or "plant" buttons.
      In Task 2, they evaluated target Japanese ideographs (while influenced by
      preceding positive or negative facial expressions as prime pictures) by pressing
      "positive" or "negative" buttons. In Task 1, the controls had the faster
      responses. In Task 2, they showed the usual congruent priming effect during very
      short prime presentations. Participants with hearing loss showed this effect only
      during short and long prime presentation times; thus, they were not superior to
      the controls in picture recognition, instead showing (a) impaired processing of
      visual information or (b) impaired perceptual-motor skills regarding quick
      responses to visual information (or both).

PMID- 15727062
TI  - Early elementary curricular alignment and teacher perspectives on standards-based
      reform.
AB  - The author investigated the alignment of reading instruction to Wisconsin Model
      Academic Standards for Reading, grades 1-4 (Wisconsin Department of Public
      Instruction, 1998a). Teachers in 18 hearing-only, 10 mixed (hearing and deaf
      students), and 8 deaf-only classrooms were study participants. Teacher groups
      demonstrated equal alignment to the standards. The study also measured teachers'
      views on standards. Teachers in hearing-only and deaf-only classrooms scored
      higher on a scale measuring receptivity toward standards than teachers in mixed
      classrooms. Teachers in hearing-only classrooms considered the standards good
      guidelines though perhaps too prescriptive. Teachers in deaf-only and mixed
      classrooms viewed standards as tools to ensure equity for students but also
      focused on challenges like the emphasis on phonetics and their need to include
      sign in deaf students' instruction. Limitations include the challenge of
      generalizing standards-based analysis, the small number of participants, and use
      of self-report measures of classroom instruction.

PMID- 15727063
TI  - T-cell depletion and immunity to malaria in HIV-infections.
AB  - Although early reports on HIV and malaria in co-infected subjects indicated
      little apparent interaction between the two infections, more recent
      investigations have found evidence for HIV increasing the risk from malaria.
      Conversely, increased viral load in susceptible cells occurs in malaria-infected
      people. However, the overall pattern of results is still somewhat confusing and
      contradictory. While morbidity from malaria may be greater in HIV-positive
      patients and in several reports the mortality risk is also higher, major
      increases in blood-stage parasitaemias that one might expect are not generally
      observed. The results of surveys are summarized and discussed in the context of
      what is known of malaria and HIV immunology in the light of recent data from
      humans as well as animal models.

PMID- 15727064
TI  - Seasonal variation in Sarcocystis species infections in goats in northern Iraq.
AB  - We investigated the prevalence of sarcocystosis in 826 goats slaughtered in the
      winter season from November to April in northern Iraq. The prevalence of
      macrocysts was on average 34%, with only 20% infected animals in November, but
      46% in February. The infection rate in 1-, 3- and 6-year-old goats was 4%, 48%,
      and 83%, respectively. The highest specificity of infection was in the oesophagus
      (99%) and the lowest in the diaphragm (3%). Grossly, we identified 2 forms of
      macroscopic sarcocysts, fat and thin, with different morphological
      characteristics. The prevalence of microcysts was 97% and no effects of age, sex
      and seasonal variations were observed. Development of microcysts in the small
      intestine of dogs and cats has also been investigated. The pre-patent period in
      experimentally infected dogs was 12-14 days and the patent period lasted 64-66
      days. A dog shed about 155 million sporocysts, but no sporocysts were shed by
      cats that had been fed the same infected tissues, thus identifying the microcysts
      as Sarcocystis capracanis.

PMID- 15727065
TI  - Characterization of SSU and LSU rRNA genes of three Trypanosoma (Herpetosoma)
      grosi isolates maintained in Mongolian jirds.
AB  - Trypanosoma (Herpetosoma) grosi, which naturally parasitizes Apodemus spp., can
      experimentally infect Mongolian jirds (Meriones unguiculatus). Three isolates
      from A. agrarius, A. peninsulae, and A. speciosus (named SESUJI, HANTO, and AKHA
      isolates, respectively) of different geographical origin (AKHA from Japan, and
      the others from Vladivostok), exhibited different durations of parasitaemia in
      laboratory jirds (2 weeks for HANTO, and 3 weeks for the others). To assess the
      genetic background of these T. grosi isolates, their small (SSU) and large
      subunit (LSU) ribosomal RNA genes (rDNA) were sequenced along with those of 2
      other Herpetosoma species from squirrels. The SSU rDNA sequences of these 3
      species along with available sequences of 3 other Herpetosoma trypanosomes (T.
      lewisi, T. musculi and T. microti) seemed to reflect well the phylogenetic
      relationship of their hosts. Three isolates of T. grosi exhibited base changes at
      2-6 positions of 2019-base 18S rDNA, at 5-29 positions of 1817/1818-base 28Salpha
      rDNA, or 1-5 positions of 1557-1559-base 28Sbeta rDNA, and none was separated
      from the other 2 isolates by rDNA nucleotide sequences. Since base changes of
      Herpetosoma trypanosomes at the level of inter- and intra-species might occur
      frequently in specified rDNA regions, the molecular analysis on these regions of
      rodent trypanosomes could help species/strain differentiation and systematic
      revision of Herpetosoma trypanosome species, which must be more abundant than
      presently known.

PMID- 15727066
TI  - Aggregation of Argulus coregoni (Crustacea: Branchiura) on rainbow trout
      (Oncorhynchus mykiss): a consequence of host susceptibility or exposure?
AB  - By sampling individual rainbow trout, Oncorhynchus mykiss, at a fish farm we
      showed that Argulus coregoni were aggregated within their host population. The
      relative significance of susceptibility and exposure generating the observed
      pattern was tested using experimental infections. We examined, whether rainbow
      trout developed protective resistance mechanisms against the louse following a
      challenge infection and if there was variation between individual trout in their
      susceptibility to A. coregoni metanauplii. Fish were exposed to 20 A. coregoni
      for 5, 25, 50, 85 or 120 min and the numbers attaching recorded. Three weeks
      later, developing argulids were removed and the experiment repeated with a
      standardized exposure of 20 metanauplii. Prior exposure of fish with A. coregoni
      did not reduce the total infection intensity compared to naive fish, but fish
      gained infection more rapidly. We suggest that there is no protective acquired
      resistance of pre-exposed rainbow trout to subsequent Argulus exposure. The
      possibility that an immunosuppressive mechanism by argulids was acting enabling
      the higher attachment rate could be refuted since control individuals, not
      previously exposed to lice, gained the infection at a similar rate as the fish
      challenged twice. Our results do not indicate clear differences in susceptibility
      among individual fish but the transmission of metanauplii on fish seemed to be
      opportunistic and non-selective. Our results support the view that variation in
      exposure time, rather than differences in susceptibility of individual hosts,
      might be the key factor in generating the aggregated distribution of Argulus on
      their hosts.

PMID- 15727067
TI  - Chronology of parasite-induced alteration of fish behaviour: effects of parasite
      maturation and host experience.
AB  - We monitored temporal changes in the magnitude of altered host behaviour in
      minnows (Pimephales promelas) experimentally infected with metacercariae of a
      brain-encysting trematode (Ornithodiplostomum ptychocheilus). This parasite
      develops and then encysts in a region of the brain that mediates the optomotor
      response (OMR), an innate behaviour that links visual stimuli with motor
      performance. The OMR of infected and uninfected minnows was evaluated between 0
      and 10 weeks post-infection (p.i.), an interval spanning the development period
      of metacercariae to infectivity in birds. Trials involved monitoring the time an
      individual minnow spent following a spinning drum that had been painted with
      alternating black and white stripes. At 2 and 4 weeks p.i., infected minnows
      followed the drum 40% less often than controls. Differences between controls and
      infected fish declined thereafter, and were undetectable by 10 weeks p.i. Both
      control and infected fish habituated equally rapidly to the spinning drum.
      However, the difference in performance between controls and infected fish was 29%
      for experienced fish and 48% for fish that had never experienced the drum.
      Because maximum parasite-induced reduction in OMR coincided with the period of
      maximum parasite development, the behavioural effects are most likely due to
      unavoidable pathology in the brain associated with developing larvae.

PMID- 15727068
TI  - Long-term investigation of the composition and richness of intestinal helminth
      communities in the stocked population of eel, Anguilla anguilla, in Neusiedler
      See, Austria.
AB  - Data from a long-term study of the intestinal helminth parasite community of
      eels, Anguilla anguilla, stocked into the shallow eutrophic Neusiedler See,
      Austria, were collected over an 8 year period (1994-2001). In total, 720 eels
      from 2 sampling sites were examined. The parasite community showed
      characteristics similar to those in the natural eel populations in rivers of the
      UK and mainland Europe: it was species poor, with only 5 species (Acanthocephalus
      lucii, Acanthocephalus anguillae, Raphidascaris acus, Proteocephalus
      macrocephalus, Bothriocephalus claviceps) comprising the component community and
      a maximum infracommunity richness of 4 species. Over the period, the intestinal
      parasite community of the sampling site in Illmitz, which was originally
      dominated by A. lucii, changed. As levels of A. anguillae increased to a point at
      which it dominated the community, diversity increased whilst dominance of a
      single species decreased. By contrast the community in the southern sampling site
      remained rather constant with a continuous high infection level of A. anguillae
      and low abundance of A. lucii. Both acanthocephalan species exhibited higher
      infection levels in larger eels and in different seasons of the year and the
      infection parameters were significantly different between the years of study. The
      significant differences in the infection levels of the 2 acanthocephalan species
      at the 2 sampling sites were surprising as both acanthocephalan species use the
      same intermediate host, Asellus aquaticus, and the sampling sites were in close
      proximity and were similar in terms of water quality, host size and invertebrate
      abundance. Differences in the fish communities of the 2 sampling sites and eel
      movements rather than interspecific competition are discussed as possible
      explanations for the differences in the parasite communities of the 2 sampling
      sites.

PMID- 15727069
TI  - Effects of host habitat quality on the viability of Cryptocotyle lingua
      (Trematoda: Digenea) cercariae.
AB  - In an earlier study it was shown that Cryptocotyle lingua cercariae, matured in
      Littorina littorea from a polluted marine lagoon, displayed slower horizontal
      swimming rates, and reduced longevity compared to cercariae released by
      periwinkles from a cleaner environment. This work investigated whether the
      pollution-induced reduction in swimming rates was due to an inefficient swimming
      action or the adoption of a less direct swimming path. In addition, cercariae
      from L. littorea that had been transferred from an 'unpolluted' to a 'polluted'
      site for 1 month provided information on the speed with which pollutants affect
      cercariae through their intermediate hosts. Results indicated that, in general,
      horizontal swimming rates were reduced due to slower swimming rather than
      disorientation and longer swimming pathways. Effects of host transplantation to a
      polluted site were clearly evident after 1 month. Evidence suggested that the
      pollutants accumulated by the cercariae via their first intermediate host
      affected the neuromusculature associated with swimming performance rather than
      sensory structures. Bearing in mind the reduced viability of C. lingua cercariae
      in polluted sites it is assumed that high prevalence of this digenean in
      gastropods (at such sites) must be due to their continual introduction by
      infected birds attracted to these habitats from other areas.

PMID- 15727070
TI  - Assessment of the anthelmintic effect of natural plant cysteine proteinases
      against the gastrointestinal nematode, Heligmosomoides polygyrus, in vitro.
AB  - We examined the mechanism of action and compared the anthelmintic efficacy of
      cysteine proteinases from papaya, pineapple, fig, kiwi fruit and Egyptian
      milkweed in vitro using the rodent gastrointestinal nematode Heligmosomoides
      polygyrus. Within a 2 h incubation period, all the cysteine proteinases, with the
      exception of the kiwi fruit extract, caused marked damage to the cuticle of H.
      polygyrus adult male and female worms, reflected in the loss of surface cuticular
      layers. Efficacy was comparable for both sexes of worms, was dependent on the
      presence of cysteine and was completely inhibited by the cysteine proteinase
      inhibitor, E-64. LD50 values indicated that the purified proteinases were more
      efficacious than the proteinases in the crude latex, with purified ficin, papain,
      chymopapain, Egyptian milkweed latex extract and pineapple fruit extract
      containing fruit bromelain, having the most potent effect. The mechanism of
      action of these plant enzymes (i.e. an attack on the protective cuticle of the
      worm) suggests that resistance would be slow to develop in the field. The
      efficacy and mode of action make plant cysteine proteinases potential candidates
      for a novel class of anthelmintics urgently required for the treatment of humans
      and domestic livestock.

PMID- 15727071
TI  - Medium-term temporal stability of the helminth component community structure in
      bank voles (Clethrionomys glareolus) from the Mazury Lake District region of
      Poland.
AB  - The structure of helminth communities in wild rodents is subject to seasonal
      variation, and is dependent on host age within years. Although between-year
      variation has been monitored, seldom has it been assessed rigorously by
      appropriate multifactorial analysis with potentially confounding factors taken
      into account. In this study we tested the null hypothesis that despite seasonal,
      host age and sex effects, helminth communities should show relative stability
      between years. Over a period of 3 years (1998-2000) we sampled bank vole
      (Clethrionomys glareolus) populations (total n = 250) at 2 points in the year: in
      spring, at the start of the breeding season, and in autumn, after the cessation
      of breeding. In spite of seasonal differences and strong age effects, the between
      year effects were surprisingly small. Measures of component community structure
      (Berger-Parker dominance index, the dominant species, S. petrusewiczi) did not
      vary, or varied only slightly from year to year. The majority of measures of
      infracommunity structure [Brillouin's index of diversity, prevalence of all
      helminths combined, prevalence and abundance of H. mixtum (the most prevalent
      helminth), mean species richness] did not differ significantly between years when
      other factors such as age, sex and seasonal variation had been taken into
      account. Some between-year variations were found (at the component community
      level, Simpson's index of diversity; at the infracommunity level, prevalence and
      abundance of S. petrusewiczi and abundance of all helminths combined), but even
      these were modest in comparison to seasonal and age differences, and were
      primarily attributable to S. petrusewiczi. We conclude that despite dynamic
      within-year fluctuations, helminth communities in bank voles in this region of
      Poland show relative stability across years. The sporadic occurrence of
      individual platyhelminths at low prevalence, makes little difference to the
      overall structure, which is largely maintained by the key roles played by the
      dominant intestinal nematodes of bank voles and the rarer species collectively.

PMID- 15727072
TI  - High resolution DNA fingerprinting by AFLP to study the genetic variation among
      Oesophagostomum bifurcum (Nematoda) from human and non-human primates from Ghana.
AB  - An AFLP approach was established to investigate genetic diversity within
      Oesophagostomum bifurcum (order Strongylida) from human and non-human primates.
      Evaluation of different combinations of restriction enzymes (n = 8) and primers
      (n = 29) demonstrated that the use of HindIII/BglII digested templates and
      primers with the selective nucleotides + AG/ +AC, respectively, was the most
      effective for the analysis of O. bifurcum DNA. A total of 63 O. bifurcum adults
      from human, Patas monkey, Mona monkey and Olive baboon hosts from different
      geographical regions in Ghana were subjected to analysis using this method.
      Cluster analysis revealed 4 genetically distinct groups, namely O. bifurcum from
      the Patas monkey (I), from the Mona monkey (II), from humans (III) and from the
      Olive baboon (IV). These findings were concordant with those achieved previously
      using RAPD analysis and supports population genetic substructuring within O.
      bifurcum according to host species. The results demonstrated the effectiveness of
      the present AFLP method for establishing genetic variation within O. bifurcum,
      and indicates its applicability to other parasitic nematodes of human and/or
      veterinary health importance.

PMID- 15727073
TI  - Molecular determination of the origin of acephalic cysticercus.
AB  - Acephalic cysticercus (Ac), a rarely developed multilobulated and nonencysted
      form of larval Taenia, causes hydrocephalus or adhesive arachnoiditis in the
      ventricles and subarachnoidal space that often lead to fatal outcome in affected
      patients. Ac has been proposed to originate from T. solium on the basis of
      morphological features, while no molecular data supporting the presumption have
      been available. In the present study, we investigated the immunological
      properties as well as molecular characteristics of Ac that was obtained
      surgically from 6 patients. Immunoblotting of the cyst fluid from Ac samples
      demonstrated the constitutive expression of a T. solium metacestode (TsM) 10 kDa
      protein. Specific antibodies against the truncated 10 kDa protein, which appears
      to be species specific for TsM cysticercosis, were detected in both serum and
      cerebrospinal fluid samples of Ac patients. Nucleotide sequences of mitochondrial
      cytochrome c oxidase subunit I (COI) and NADH dehydrogenase subunit 1 (ND1) genes
      of Ac were almost identical to those of T. solium but differed substantially from
      those of the other Taenia species. In phylogenetic analysis, Ac clustered with T.
      solium in a well-supported clade. Our results strongly suggest that Ac may have
      originated from T. solium.

PMID- 15727074
TI  - Fifteen years single center experience in the management of progressive familial
      intrahepatic cholestasis of infancy.
AB  - Recent advances in genetics and in physiopathology of bile composition and
      excretion have clarified the understanding of progressive familial intrahepatic
      cholestasis (PFIC). The aim of the present study is to review the experience of
      our center in terms of diagnosis, management and outcome of 49 pediatric PFIC
      patients, belonging to the three classical subtypes described. We analyse the
      clinical, biological, and histological patterns and review the response to the
      medical and surgical treatment and the global outcome. The only clinical
      difference between the different subtypes of PFIC patients was the intensity of
      pruritus. Serum gamma-glutamyltransferase (GGT) and liver histology allowed to
      differentiate PFIC III from PFIC I and II patients. High levels of biliary bile
      acids in 2 low-GGT patients was associated with favourable outcome. Response to
      ursodeoxycholic acid (UDCA) varies from patient to patient and was not associated
      to a particular subtype of PFIC. In five patients of this cohort, external
      biliary diversion was performed without improvement. Transplantation is indicated
      whenever medical treatment fails to restore normal social life, growth and well
      being of the child and it is associated with excellent survival (> 90%).

PMID- 15727075
TI  - Non-endoscopic diagnosis of multifocal atrophic gastritis; efficacy of serum
      gastrin-17, pepsinogens and Helicobacter pylori antibodies.
AB  - BACKGROUND/AIMS: Infection with H. pylori is an important risk factor for the
      development of gastric cancer and glandular atrophy is an intermediate stage in
      gastric carcinogenesis. While screening the patients with atrophic gastritis by
      endoscopy is unrealistic, a concept of "serological gastric biopsy" based on
      measurement of gastric secretory proteins and peptides should be further
      validated. We sought to determine if the laboratory panel composed of serum PGI
      and protein stimulated gastrin-17 might select patients with MAG, and what is
      diagnostic significance of H. pylori serology in population of high prevalence of
      H. pylori infection. MATERIAL AND METHODS: 55 consecutive patients of both sexes
      (M/F 25/30; range of age 55 -81 years) were referred for gastroscopy with antrum
      and corpus mucosal biopsies. Patients with histological signs of glandular
      atrophy at any site of the stomach were considered to have multifocal atrophic
      gastritis. A first blood sample was collected for measurement of basal gastrin
      17, pepsinogens and H. pylori IgG-antibodies, and second was taken 20 minutes
      after use of protein-rich drink to measure stimulated gastrin-17. RESULTS: Signs
      of mucosal atrophy were found in 19 patients, while 29 patients showed non
      atrophic gastritis and seven H. pylori-negative patients had no histological
      pathology. Low serum level of stimulated gastrin-17 (< 5 pmol/l) and/or
      pepsinogen I (< 50 microg/l), were found in 16 of 19 patients (84.2%) with and in
      7 of 36 patients (19.4%) without atrophy in the histological study. Combining of
      H. pylori serology with serum levels of secretory peptides had no significant
      effect on diagnostic sensitivity of the test panel. CONCLUSION: The test panel
      composed of pepsinogen I and protein stimulated gastrin-17 may be used as the
      "serological gastric biopsy" detecting multifocal atrophic gastritis. The
      diagnostic sensitivity of this test panel is not increased by knowledge of H.
      pylori status.

PMID- 15727076
TI  - Role of chronic atrophic gastritis of the body-fundus and achlorhydria in the
      development of epithelial dysplasia and gastric carcinoma.
AB  - BACKGROUND/AIM: Chronic atrophic gastritis of the body-fundus with hypo
      achlorhydria has been long since considered the precursor of gastric cancer (GC).
      A study has been made about the histological pattern of the body-fundic mucosa
      (oxyntic area) in course of preneoplastic lesions (epithelial dysplasia),
      associated or progressed to gastric cancer, in order to evaluate the real
      association with chronic atrophic gastritis and, therefore, with a reduced acid
      secretion. METHODOLOGY: The study of the histological condition of the body
      fundic mucosa and of the acid secretion has been effected in 120 cases of
      epithelial dysplasia (ED) from January 1990 to November 1997. The casuistry is
      composed of 70 cases of low grade dysplasia (LGD) and 50 cases of high grade
      dysplasia (HGD). Gastric biopsy specimens were studied for dyspepsia: for each
      patient, at least 8 specimens were obtained from the lesion area and in
      surrounding areas. Besides, at least 4 biopsies have been performed in the
      opposite gastric region. ED diagnosis was effected according to well defined
      criteria. The histological study of gastric mucosa in gastritis was effected or
      revised in accordance with the updated Sydney system (Houston). Stimulated acid
      secretion was expressed as Maximal Acid Output (MAO), which is the amount of HCl
      produced in one hour, following stimulation with pentagastrin (6 micro-g/kg). The
      clinical outcome subdivision of ED was made using the criteria of Rugge et al.
      (12). RESULTS: HGD significantly associates with GC in comparison with LGD. The
      histological evaluation of the oxyntic area shows severe chronic atrophic
      gastritis (SCAG) in a low percentage of cases (15/120: 12.5%): LGD 9/70: 12.85% ;
      HGD 6/50: 12%. Complete achlorhydria has been noted in 5 cases of LGD and in 1
      case of HGD only. In case of GC (43 subjects) SCAG has been evidenced in 10 cases
      and complete achlorhydria in 5 cases. CONCLUSIONS: From the data of the present
      experience emerges that the presence of SCAG of the oxyntic area in course of ED
      or early GC is limited to a low percentage of cases. Such concepts induce to
      modify some indications related to the endoscopic surveillance and, in accordance
      with the American Society of Gastrointestinal Endoscopy we are stating that there
      are no sufficient data to support subsequent endoscopic surveillance for the
      subjects with atrophic gastritis.

PMID- 15727077
TI  - Oral fluoropyrimidines in colorectal cancer: a door open to the future?
AB  - Since its first use 40 years ago, 5-fluorouracil (5-FU) has become an
      unquestionable component of colorectal cancer treatment. It is also now well
      established that infusional 5-FU administration, in combination with leucovorin,
      is associated with better tolerance and at least equal efficacy than bolus
      administration. However, requiring catheter and infusion pumps, infusional 5-FU
      administration is costly, rather inconvenient for patients and potentially
      associated with morbidity, initiating subsequent oral chemotherapy development.
      To address intravenous 5-FU related issues, oral fluoropyrimidines have been
      developed such as capecitabine, preferentially converted to 5-FU into tumour
      cells, and UFT, able of bypassing intestinal dihydropyrimidine dehydrogenase. We
      discuss in this article current oral fluoropyrimidines achievements in colorectal
      cancer management.

PMID- 15727078
TI  - Medical treatment of portal hypertension.
AB  - Prevention of the first variceal haemorrhage should start when the patients have
      developed medium sized to large varices. Non-selective beta-blockers are the
      first-line treatment; band ligation is roughly equivalent to beta-blockers and is
      the first choice for patients with contraindications or intolerance to beta
      blockers. Treatment of acute bleeding should aim at controlling bleeding and
      preventing early rebleeding and complications, especially infections. Combined
      endoscopic and pharmacological treatment with vasoactive drugs can control
      bleeding in up to 90% of patients. All patients who survive a variceal bleed
      should be treated with beta-blockers or band ligation to prevent rebleeding. All
      patients in whom bleeding cannot be controlled or who continue to rebleed can be
      treated with salvage TIPS or, in selected cases, with surgical shunts. Liver
      transplantation should be considered for patients with severe liver insufficiency
      in which first-line treatments fail.

PMID- 15727079
TI  - Autoimmune pancreatitis with evolution to cholangitis: a case report.
AB  - We report the case of a 47-year-old Caucasian male patient who presented with
      obstructive jaundice and mild epigastric pain. Autoimmune pancreatitis was
      diagnosed based on magnetic resonance imaging, biopsy and clinical evolution, and
      the patient was successfully treated with corticosteroids. However, a few months
      later ERCP showed an image compatible with sclerosing cholangitis. Again,
      treatment with corticosteroids was given, after which the bile ducts became
      normal. A few months later, again there was a relapse and azathioprine was
      started. After decreasing the dose of immunesuppression, we saw relapses of
      cholangitis and pancreatitis, with eventually evolution to chronic calcifying
      pancreatitis. The aim of this report is to describe autoimmune pancreatitis as a
      cause of obstructive jaundice, and to illustrate that evolution to an
      immunesuppression-responsive cholangitis, with evolution to chronic calcifying
      pancreatitis is possible. Also, our patient had a small fluid collection,
      possibly a pseudocyst, an unusual finding in autoimmune pancreatitis, which
      disappeared during treatment.

PMID- 15727080
TI  - Spontaneous rupture of omental varices: an uncommon cause of hypovolemic shock in
      cirrhosis.
AB  - In cirrhotic patients, esophageal and esophagogastric varices are the most common
      sites of bleeding, often responsible for hypovolemic shock. Hepatocellular
      carcinoma, blunt abdominal trauma and postprocedural complications are classical
      causes of hemoperitoneum in hepatic cirrhosis. Rupture of omental varices is
      another and rarely reported cause of shock in cirrhosis. We report a case of
      hypovolemic shock caused by ruptured omental varices. Selective review of
      literature regarding presentation, diagnosis and management of ruptured
      intraabdominal varices is also part of presentation.

PMID- 15727081
TI  - Hepatitis caused by occupational chronic exposure to trichloroethylene.
AB  - Trichloroethylene (TCE) is an organic solvent used in a variety of industries for
      more than 60 years. Several adverse events following acute or chronic exposure to
      trichloroethylene have been reported. However, TCE-induced hepatitis is very
      rare. We present the case of a 55-year old male who was presented with anorexia,
      fatigue and upper abdominal discomfort. Routine laboratory examination revealed
      marked elevation of liver enzyme values. All possible causes of hepatitis were
      ruled out. The patient has been working as a shoemaker, in a small room of a
      basement, with insufficient air-exchange; during the last 5 years he used daily a
      glue containing 1,1,1 trichloroethylene. The diagnosis of hepatitis was confirmed
      by liver biopsy. The offending agent was withdrawn. Three months later, he was
      "feeling well" and liver enzyme values had returned to normal. Six months after
      the initial biopsy, a second liver biopsy was performed and histology was
      markedly improved. Workers exposed to hazardous chemicals, such as
      trichloroethylene, must have periodic follow-up examinations. Good work practices
      are very important when using toxic substances. In patients whose initial
      diagnostic workout is negative for common causes of acute or chronic hepatitis,
      toxic causes should be considered, with emphasis on patient's job and working
      conditions.

PMID- 15727082
TI  - Nodular regenerative hyperplasia of the liver and Hodgkin's disease: a case
      report.
AB  - Nodular regenerative hyperplasia (NRH) of the liver is a rare entity
      characterized by the presence of nodules in the hepatic parenchyma, not
      surrounded by fibrous septa. The pathogenesis and etiology are unknown but an
      association with different diseases including some hematological disorders has
      been described. Its association with Hodgkin's disease is infrequent. We report
      the case of a 63 years old man who presented symptoms and signs of portal
      hypertension, hepatocellular failure with progressive deterioration and death.
      Postmortem examination disclosed Hodgkin's disease with hepatosplenic involvement
      and NRH of the liver. The association of these entities could be explained by the
      presence of portal infiltration contributing to portal venous obliteration and
      leading to portal hypertension and formation of the parenchymal nodules
      characteristic of this entity. Other mechanisms that could cause or influence
      this association can not be ruled out.

PMID- 15727083
TI  - Primary lymphoma of liver: a case report and review of literature.

PMID- 15727084
TI  - [Technetium99 labelled synthetic somatostatin analogue (depreotide) in the
      diagnosis of peripheral solitary pulmonary nodules].
AB  - Lung carcinoma is one of the most common neoplasms, both in men and women. Many
      methods are employed within diagnostics approaches in oncology, among them are
      radiological, endoscopic, cytological and isotopic ones. Synthetic proteins
      labelled with gallium (Ga67), indium (In111) or technetium (Tc99) binding with
      receptors localised on cells surface enable scintigraphic determination of
      intensive uptake sites. The aim of the study was to asses clinical usefulness of
      technetium99 labelled synthetic somatostatin analogue (depreotide) in the
      diagnosis of solitary pulmonary nodules. Thirty one patients (19 men and 12
      women) with isolated peripheral pulmonary lesions in chest X-ray examination were
      included into the study. All patients received intravenous infusion of synthetic
      protein compound, trifluorodepreotide acetate labelled with technetium99, with
      radio activity of 555-740 MBq (mega Becquerel) [Neospect--Nycomed Amersham, UK].
      Radiopharmaceutical uptake was determined by two-head gamma camera according
      SPECT method (single photon emission computed tomography) after 3-4 hours after
      an injection. Intensive radiopharmaceutical uptake by abnormal lesions was found
      in 22 patients (71%), however in 9 (29%) it was not found in the sites of
      radiological changes. Among 22 patients with intensive uptake, in 17 (77%)
      patients a diagnosis of carcinoma was confirmed and in 5 patients benign lesions
      were diagnosed. In the group of 5 patients without marker uptake single case of
      carcinoma was found and in 4 benign lesions. Four patients refused further
      invasive diagnostic procedures. The sensitivity of this method was 94% with a
      specificity of 44%. No serious adverse clinical reactions associated with 99Tc
      depreotide were observed. CONCLUSIONS: 1. Technetium99 labelled synthetic
      somatostatin analogue [(depreotide) (NeoSpect)] is safe in pulmonological and
      oncological clinical diagnostics. 2. The use of this compound is a valuable
      scintigraphic, supplementary method to qualify patients for further invasive
      diagnosis of peripheral pulmonary solitary nodules.

PMID- 15727085
TI  - [Electrocardiography and prediction of myocardial damage in patients with acute
      pulmonary embolism].
AB  - Acute pulmonary embolism (APE) may lead to myocardial necrosis detected by
      elevation of cardiac troponin levels. We tried to assess, if electrocardiographic
      abnormalities may help to define APE patients with myocardial damage and at high
      risk of complicated clinical course. Therefore we analyzed 50 patients (34F) aged
      64.6 +/- 16.9 with confirmed APE. On admission 12-lead standard ECG was recorded
      and cardiac troponin T (cTnT) was determined quantitatively (Roche). Serum cTnT
      levels > 0.01 ng/ml, regarded to indicate myocardial injury, were detected in 29
      (58%) patients. ST segment depression in ECG was found in 24% of all patients and
      was more frequent in cTnT + then in group without myocardial injury (41.4% vs 0%,
      p=0.004). Complicated clinical course and death in acute pulmonary embolism were
      also more frequently observed in group with ST segment depression (47.1% vs
      12.1%, p = 0.03 and 75.0% vs 14.3%, p = 0.02 respectively). Although negative T
      waves were slightly more frequent in patients with elevated serum troponin T
      level (65.5% vs 42.9%) and in patients, who died of pulmonary embolism (62.5% vs
      54.8%), the difference did not reach statistical significance. CONCLUSION: ST
      segment depression detected in standard ECG in patients with APE suggests
      myocardial injury and may indicate unfavourable clinical course.

PMID- 15727086
TI  - [Evaluation of the effectiveness of extensive, ambulatory, non-pharmacological
      obesity treatment program].
AB  - The aim of the study was an attempt to answer following questions: 1. Is
      extensive, non-pharmacological obesity treatment programme effective and is
      reduced body weight likely to be maintained in the long term? 2. What is the
      influence of the programme on some components of metabolic syndrome? 3. What is
      the effect of the programme on levels of leptin and insulin as indexes of weight
      reduction effectiveness? An informed consent to participate in the treatment was
      given by 37 women (GB) aged 19-47 yrs. (mean 36 +/- 7.7); with BMI 36 +/- 4.9
      kg/m2. Control group (GK) was composed of 16 women aged 21-40 yrs. A 3-month
      extensive, ambulatory, non-pharmacological obesity treatment programme was
      offered to study subjects. Anthropometric, biochemical and hormonal assessment
      was performed before treatment (0), after 3 months--at the end of treatment (3),
      and after one year (R). After 3 months a reduction of body weight was observed in
      34 persons (92%) whereas in 1 person (2.7%) body weight was stable and in 2
      (5.4%) body weight increased. Body weight reduction was accompanied by beneficial
      changes in metabolic parameters. After one-year follow-up reduced body weight was
      maintained in 33 persons (89%), however, insulin and leptin levels and HOMA index
      increased significantly when compared to those observed during active treatment
      and were comparable with initial values. In the control group a significant
      increase in BMI, insulin and leptin levels and HOMA index was observed after one
      year follow-up. CONCLUSIONS: 1. The extensive, non-pharmacological obesity
      treatment programme is effective because enables the reduction of body weight by
      10% and patients are likely to maintain reduced body weight for one year. 2. The
      programme brings out metabolic benefits and enables to maintain them after its
      discontinuance. 3. The rebound increase in leptin and insulin levels after 9
      months since active treatment has been discontinued may be an unfavourable
      prognostic factor in terms of maintenance of reduced body weight and indicates
      that the programme should be repeated in some patients groups.

PMID- 15727087
TI  - [Body surface heart potential mapping in the limited lead system].
AB  - A goal of the presented study was to analyze and assess the information collected
      in the assigned electrocardiographic (ECG) arrangement, constituting a
      "transition" between the two systems of which one is a 87-lead cylindrical
      system, and the second one is a 30-lead spherical system. The transient 30
      electrode arrangement has been selected from the 87-lead ECG network with the
      arbitrarily assigned electrodes location, which corresponded to the spherical
      network called "diamentoid". A subject of the visual inspection and analysis were
      isopotential and isointegral maps created in the three following lead systems:
      "total", 87-lead cylindrical system; "transient", 30-lead (limited lead) system,
      and 30-lead spherical system derived from the latter as a result of the
      diamentoid transformation. The performed comparisons were focused on determining
      the similarities and differences between the maps gained from the "full" and
      "limited" lead systems. The maps representing the entire cardiac cycle,
      constructed on the base of the ECG recordings obtained from the 53 patients, were
      assessed. The maps, covering the complex QRS divided in the eight portions, were
      subjected to the detailed analysis. As the result of the comparative analysis of
      the body surface maps generated in the given three lead systems, it could be
      concluded that isopotential and isointegral maps from the both 30-lead systems
      are capable to retain the significant information concerning the features of
      potentials distribution, as compared with the data provided by the 87-lead
      system.

PMID- 15727088
TI  - [Platelet-monocyte aggregate formation in patients with coronary heart disease
      and disorders of carbohydrate metabolism].
AB  - Circulating monocyte-platelet aggregates can release procoagulant, oxidative and
      mitogenic factors, thereby contributing to arterial thrombosis. The aim of our
      study was the estimation of heterophilic leukocyte-platelet aggregates in
      patients referred for coronary angiography, dependent on the degree of coronary
      stenosis and the disturbances of carbohydrate metabolism. Flow-cytometric
      analysis was performed in 50 consecutive patients with positive exercise test
      (age 54.2 +/- 6.4 years): 27 with normal glucose tolerance, 7 with impaired
      glucose tolerance and 16 with type 2 diabetes, and in 16 healthy subjects (age
      44.8 +/- 14.1 years). We found that patients with coronary heart disease had
      increased leukocyte-platelet aggregate formation in comparison to the controls
      (the percentage of monocyte-platelet aggregates 47.5 +/- 23.0 vs 25.7 +/-12.8, p
      = 0.003, mean fluorescence intensity (MIF) 187.6 +/- 117.2 vs 79.3 +/- 42.8, p =
      0.002, the percentage of granulocyte-platelet aggregates 20.7 +/- 10.4 vs 17.0 +/
      3.6, p = 0.009, MIF 64.2 +/- 41.3 vs 40.9 +/- 6.3, p = 0.008). The highest
      percentage of heterophilic aggregates was observed in patients with 1- and 2
      vessel disease and those with "clean" vessels. In diabetic patients the
      percentage and MIF of granulocyte-platelet aggregates were decreased in
      comparison to the subjects with normal glucose tolerance (16.7 +/- 7.2 vs 22.8 +/
      9.8, p = 0.03 and 44.3 +/- 10.8 vs 74.4 +/- 48, p = 0.009, respectively). There
      was no increase in glycoprotein CD14 expression in any of the group studied. We
      found a positive correlation between the percentage of monocyte-platelet
      aggregates and fasting insulin level (r = 0.369, p = 0.04) and a negative
      correlation between MIF of monocyte-platelet aggregates and HDL level (r = 
      0.459, p = 0.012), between MIF CD14 and HDL level (r = -0.435, p = 0.02), and
      between the percentage of granulocyte-platelet aggregates and postprandial
      glycaemia (r = -0.4117, p = 0.03). We concluded that: 1. the patients with
      "clean" vessels represent a group of high atherothrombotic risk. 2. the patients
      with minimal coronary stenosis may benefit from anti-inflammatory and
      antiplatelet treatment.

PMID- 15727089
TI  - [12-month outcomes of diabetic and non-diabetic patients with acute coronary
      syndromes assigned to early invasive treatment strategy].
AB  - INTRODUCTION: Epidemiological studies show that diabetes mellitus is a serious
      medical, economic and public health problem. 21-30% of patients with acute
      coronary syndromes (ACS) have diabetes. We aimed at assessing the in-hospital and
      12-month outcomes of diabetic and non-diabetic patients with ACS without ST
      segment elevation. METHODS: 329 consecutive patients with ACS without ST-segment
      elevation were entered into the study, of whom 63 patients (19.1%) had diabetes
      mellitus. The inclusion criteria were: 1) rest angina within 24 hours prior to
      admission, 2) at least one of the following: ST-segment depression (> or = 0.05
      mV), transient (< 20 min) ST-segment elevation (> or = 0.05 mV), T-wave inversion
      (> or = 0.1 mV) in at least 2 continuous leads, positive serum cardiac markers.
      All patients underwent coronary angiography and percutaneous coronary
      intervention (PCI) within the first 24 hours of admission. RESULTS: Baseline
      profiles were similar in both groups. More non-diabetic patients had initial TIMI
      3 flow (76% vs 65%, p = 0.05), whereas the rate of successful PCI (final TIMI 3
      flow) was similar in both groups (97.7% vs 96.8%, NS). The rate of GP IIb/IIIa
      inhibitors treatment was similar in both groups. Overall mortality in the
      diabetic group and in the non-diabetic group was 7.9% and 3.4% respectively (NS).
      In-hospital mortality rate was 3.2% and 1.1% respectively (NS). After discharge,
      9 patients died, of whom 3 patients were in the diabetic group and 6 patients in
      the non-diabetic group (5.0% vs 2.28% NS). The rate of MI during follow-up was
      similar in both groups. More diabetic patients had episodes of unstable angina
      during follow-up (30% vs 17.9%, p = 0.034). Primary endpoint (death, myocardial
      infarction, repeat revascularization) was more frequent in the diabetic patients
      (28.57% vs 17.67%, p = 0.05), whereas the rate of combined endpoint (death,
      myocardial infarction, repeat revascularization, cardiovascular hospitalization)
      was similar in both groups (40% vs 26.23%, NS). More diabetic patients received
      beta-blockers, diuretics and digoxin during follow-up. CONCLUSIONS: Early
      invasive treatment and intensive medical therapy improves in-hospital prognosis
      for diabetic patients, whereas diabetes mellitus affects long-term outcomes with
      more episodes of unstable angina and a more frequent rate of repeat
      revascularization.

PMID- 15727090
TI  - [Usefulness of TIMI Risk Score in assessing the prognosis in patients with acute
      coronary syndromes without ST elevation assigned to early percutaneous coronary
      intervention. Comparison of the high-risk and the moderate-risk patients].
AB  - Risk stratification in acute coronary syndromes (ACS) without ST segment
      elevation plays an important role in choosing treatment strategy and making
      further prognosis. We aimed at 1) assessing the usefulness of TIMI Risk Score in
      risk stratification and prognosis in unselected patients with ACS without ST
      elevation who underwent early percutaneous revascularization, 2) comparing the
      frequency of adverse events (death, MI, repeat revascularization in high-risk and
      moderate-risk patients during 14 days from revascularization, 3) comparing the
      efficacy of percutaneous revascularization in the high-risk and in the moderate
      risk group. High-risk (TIMI Risk Score > or = 5 points) and moderate-risk (TIMI
      Risk Score 3-4 points) group comprised 324 and 240 patients respectively. High
      risk group comprised older patients, fewer men, more diabetics and hypertensive
      patients. Peripheral vessel disease and prior MI was also more frequent in the
      high-risk group. More high-risk patients had initial TIMI flow < 3 in target
      vessel, as well TIMI 3 flow after revascularization was achieved in fewer high
      risk patients. During 14-day follow-up the frequency of combined end-point
      (death, MI, repeat revascularization) was more frequent in the high-risk group
      (8.95% vs 1.67%). TIMI Risk Score is an easy to use and useful method in risk
      stratification and prediction of adverse events in patients with ACS without ST
      segment elevation assigned to early percutaneous intervention in the early post
      procedure period.

PMID- 15727091
TI  - [Recurrent polychondritis. Presentation of two cases and a review of the
      literature].
AB  - Relapsing polychondritis is a rare, chronic disease that can involve all types of
      cartilage in different sites. The most common symptoms of relapsing
      polychondritis are features of auricular, nasal and tracheal cartilage
      inflammation. The authors presented two cases of relapsing polychondritis and
      related diagnostic and therapeutic difficulties.

PMID- 15727092
TI  - [Late diagnosis of a severe attack of acute intermittent porphyria (AIP)-
      diagnostic dilemmas].
AB  - The article presents diagnostic problems concerning the case of 54-year old woman
      with a delayed diagnosis of a severe attack of acute intermittent porphyria
      (AIP), which on admission manifested mainly as flaccid quadriplegia. The signs of
      neurological deficit were accompanied by changes in electrocardiographic
      recording that suggested acute myocardial ischaemia without apparent chest pain.
      Based upon a detailed history and identification of potential factors that might
      have triggered the attack the suspicion of acute hepatic porphyria was raised.
      The suspicion was confirmed by biochemical testing in the Institute of Hematology
      and Transfusiology in Warsaw. The treatment with glucose was administered, drugs
      contraindicated in porphyria were excluded, and early rehabilitation programme
      was instituted, which led to a marked improvement of general status and
      resolution of quadriplegia after 16 weeks. Parallel to the improvement of
      neurological status and a decrease in urinary excretion of heme precursors the
      normalisation of ECG changes was observed. The authors point out that
      differential diagnosis of abdominal pain with concomitant hyponatraemia should
      include an attack of acute porphyria since early administration of proper
      management prevents the development of life-threatening neurological signs
      accompanying the severe attack. The diagnosis of an attack of acute porphyria in
      the phase of predominant neurological signs, in the absence of abdominal pain,
      may be difficult and always warrants, apart from anamnestic data, the
      confirmation with appropriate biochemical testing.

PMID- 15727093
TI  - [Gaucher disease--one of the possible causes of splenomegaly--case report].
AB  - The aim of this article is to present a case report of Gaucher disease which was
      diagnosed in patient with hepatosplenomegaly. A 43 years old man has complained
      of weakness, stomach pain and yellowish skin color for several years. The
      severity of symptoms has increased during the last 2 years. Laboratory data
      revealed thrombocytopenia (platelet count 108 G/l) and slightly elevated
      bilirubin level (1.68 mg/dl). In ultrasound examination hepatosplenomegaly was
      observed. Computer tomography evaluated the size of the spleen to 20 x 12 cm.
      Gaucher cells were found in bone marrow. The some type of cells was recognized in
      liver biopsy. To confirm diagnosis of Gaucher disease enzyme test was performed.
      Chitotriosidase level in serum was pronouncedly increased (11,540 nmol/mg
      protein/hr) while normal level is under 150 nmol/mg protein/hr.
      Glucocerebrosidase activity in leucocytes was within the limit. Thus the enzyme
      activity was 21.8 nmol/mg protein/hr and was below the normal range which is
      between 111-455 nmol/mg protein/hr. The last assay, measuring
      glucolukocerebrosidase activity in cultured fibroblast confirmed the diagnosis of
      Gaucher disease.

PMID- 15727094
TI  - [Waldenstrom's macroglobulinemia--the experts opinion about new therapeutic
      possibilities and response criteria].

PMID- 15727095
TI  - [Effect of calcium phosphate abnormalities on atherogenesis in patients with
      chronic uremia].

PMID- 15727096
TI  - [Treatment of calcium-phosphate abnormalities decreases atherogenic process in
      patients with chronic uremia].

PMID- 15727097
TI  - [Monogenic forms of mineralocorticoid hypertension].

PMID- 15727098
TI  - [Recent advances in the diagnosis of von Willebrand disease].

PMID- 15727099
TI  - [Hemochromatosis. Indication to liver transplantation and recurrence of disease
      after transplantation].

PMID- 15727100
TI  - [National crisis discussion necessary: 2 million hypertensive patients dropped
      out?].

PMID- 15727101
TI  - [At best every 5th hypertensive patient is adequately managed].

PMID- 15727102
TI  - [Prevention of obesity begins in the uterus. Don't Super Size Us!].

PMID- 15727103
TI  - [Medical interventions and instruments become increasingly smaller. Heart valve
      replacement in the catheter laboratory].

PMID- 15727104
TI  - [Laser treatment supposedly modifies dentin. 1 visit to the dentist--an no caries
      from then on? (interview by Dr. Thomas Meissner)].

PMID- 15727105
TI  - [Honey is better than aciclovir in herpes].

PMID- 15727106
TI  - [Dying in agony with implantable defibrillator]].

PMID- 15727107
TI  - [Vestibular training improves vertigo].

PMID- 15727108
TI  - [Diagnosis of renal artery stenoses: comparison of 3 methods].

PMID- 15727109
TI  - [The family physician knows the whole story. When something affects our
      kidneys.....].

PMID- 15727110
TI  - [Management of patients with chronic renal failure].
AB  - Terminal renal failure has an incidence of approximately 60 persons per million
      population, and is on the increase. Victims suffer from an appreciably
      compromised quality of life and life expectancy. The financial burden on the
      health service imposed by the need for renal replacement therapy (dialysis or
      renal transplantation) is considerable. To achieve a therapeutic impact, the
      underlying kidney disease, as well as the factors driving progression and injury
      need to be identified as early as possible. Of particular importance in this
      connection is the rigorous management of arterial hypertension with the use of
      ACE inhibitors, dietetic measures and normalization of hemoglobin levels.

PMID- 15727111
TI  - [Diagnosis and treatment of disordered acid-base balance].
AB  - Differential diagnosis in disordered acid-base homeostasis is usually possible by
      measuring the pH, pCO2, pO2 and bicarbonate concentration, and enables
      differentiation between respiratory alkalosis and acidosis, and metabolic
      alkalosis and acidosis. Compensatory counter-regulation (respiratory or renal)
      can make correct assessment of the primary disorder problematic. Treatment of the
      underlying disease, in particular the provision of adequate oxygenation in
      respiratory disorders is of the essence. In chronic forms of metabolic acidosis,
      for example in chronic renal insufficiency and elderly patients, bicarbonate
      substitution should be initiated in order to prevent the negative effects on
      various organ systems. Sodium bicarbonate formulations that can be assimilated
      from the small bowel are especially tolerable and suitable.

PMID- 15727112
TI  - [Mild head injury].
AB  - Mild injuries to the head are a common everyday occurrence. Only one out of
      30,000 patients suffering mild traumatization of the brain subsequently goes on
      to develop a complication that requires treatment. Such patients can be
      identified on the basis of the Glasgow Coma Scale and the determination of risk
      factors, and these data also serve as an aid for deciding whether surveillance at
      home or hospitalization is indicated.

PMID- 15727114
TI  - [Many open problems with the electronic health record. Is a soundproof room
      mandatory for every general practice?].

PMID- 15727115
TI  - [Now also cost schedules for medical aids. Prevent patient protests now].

PMID- 15727113
TI  - [Selective serotonin and noradrenaline reuptake inhibitors: a step forward in the
      treatment of depression?].
AB  - With the tricyclics, selective serotonin reuptake inhibitors (SSRIs) and other
      substances, we now have available a range of medications for the treatment of
      depression and other psychological disorders (e.g. anxiety, panic). Nevertheless,
      only some of the patients experience a remission of their depressive symptoms.
      The occurrence of side effects and the only modest level of effectiveness result
      in inadequate compliance on the part of the patient. With venlafaxine and
      duloxetine two representatives of the selective serotonin and noradrenaline
      reuptake inhibitor (SSNRI) class of antidepressants are now available. SSNRIs
      have a dual effect coupled with high selectivity. The present article the extent
      to which this particular action mechanism results in an improved clinical
      efficacy and tolerability profile of the SSNRIs, in particular in comparison with
      SSRIs.

PMID- 15727116
TI  - [Stress echocardiography. Stress for the heart--diagnostic aid for the
      cardiologist].

PMID- 15727117
TI  - [Gardening with sequelae]].

PMID- 15727118
TI  - Message from the president: A new year for caring.

PMID- 15727119
TI  - Inventing science.

PMID- 15727120
TI  - Chemical proteomics applied to target identification and drug discovery.

PMID- 15727121
TI  - Chimerization of multiple antibody classes using splice overlap extension PCR.

PMID- 15727122
TI  - Laboratory-based monitoring of an insect-transmitted plant pathogen system.

PMID- 15727123
TI  - Buccal swabbing and extraction of high quality sunfish (Lepomis) DNA for use in
      PCR analysis.

PMID- 15727124
TI  - Purification of filamentous bacteriophage for phage display using size-exclusion
      chromatography.

PMID- 15727126
TI  - Light emitting diode microscope illumination for green fluorescent protein or
      fluorescein isothiocyanate epifluorescence.

PMID- 15727127
TI  - Functional promoter analysis using an approach based on an in vitro evolution
      strategy.
AB  - In vitro evolution imitates the natural evolution of genes and has been very
      successfully applied to the modification of coding sequences, but it has not yet
      been applied to promoter sequences. We propose an alternative method for
      functional promoter analysis by applying an in vitro evolution scheme consisting
      of rounds of error-prone PCR, followed by DNA shuffling and selection of mutant
      promoter activities. We modified the activity in embryogenic sugarcane cells of
      the promoter region of the "Goldfinger" isolate of banana streak virus and
      obtained mutant promoter sequences that showed an average mutation rate of 2.5%
      after applying one round of error-prone PCR and DNA shuffling. Selection and
      sequencing of promoter sequences with decreased or unaltered activity allowed us
      to rapidly map the position of one cis-acting element that influenced promoter
      activity in embryogenic sugarcane cells and to discover neutral mutations that
      did not affect promoter function. The "selective-shotgun" approach of this
      promoter analysis method immediately after the promoter boundaries have been
      defined by 5' deletion analysis dramatically reduces the labor associated with
      traditional "linker-scanning" deletion analysis to reveal the position of
      functional promoter domains. Furthermore, this method allows the entire promoter
      to be investigated at once, rather than selected domains or nucleotides,
      increasing the prospect of identifying interacting promoter regions.

PMID- 15727125
TI  - Useful tool to generate unidirectional deletion vectors by utilizing the star
      activity of BamHI in an NcoI-BamHI-XhoI cassette.

PMID- 15727128
TI  - High-throughput mouse genotyping using robotics automation.
AB  - The use of mouse models is rapidly expanding in biomedical research. This has
      dictated the need for the rapid genotyping of mutant mouse colonies for more
      efficient utilization of animal holding space. We have established a high
      throughput protocol for mouse genotyping using two robotics workstations: a
      liquid-handling robot to assemble PCR and a microfluidics electrophoresis robot
      for PCR product analysis. This dual-robotics setup incurs lower start-up costs
      than a fully automated system while still minimizing human intervention.
      Essential to this automation scheme is the construction of a database containing
      customized scripts for programming the robotics workstations. Using these scripts
      and the robotics systems, multiple combinations of genotyping reactions can be
      assembled simultaneously, allowing even complex genotyping data to be generated
      rapidly with consistency and accuracy. A detailed protocol, database, scripts,
      and additional background information are available at
      http://dir.nhlbi.nih.gov/labs/ldb-chd/autogene/.

PMID- 15727129
TI  - Mapping transposon insertion sites by touchdown PCR and hybrid degenerate
      primers.
AB  - A novel mapping method based on touchdown PCR was developed for identifying a
      transposon insertion site in genomic DNA using a hybrid consensus-degenerate
      primer in combination with a specific primer that anneals to the transposon. The
      method was tested using Xanthomonas citri transposon mutants. PCR products
      contained adjacent DNA regions that belonged to both X. citri genomic DNA and the
      transposon. Products were directly sequenced from PCRs using only the specific
      primer. Different PCR conditions were tested, and the optimized reaction
      parameters that increased product yields and specificity are described. Best
      results were obtained with the HIB17 hybrid primer, which is a 25-mer
      oligonucleotide having degenerate bases at 6 different positions within the last
      12 bases at the 3' end. An X. citri mutants library was produced by random
      transposition using the EZ::TN <KAN-2> transposon, and we identified the
      insertion sites within the genome of 90 mutants. Insertions were found within
      both the chromosomal and the plasmid DNA in these X. citri mutants. Restriction
      mapping and Southern blot analysis confirmed the insertion sites for eight
      randomly chosen mutants. This method is a very useful tool for large-scale
      characterization of mutants in functional genomics studies.

PMID- 15727130
TI  - Techniques in plant telomere biology.
AB  - The role model systems have played in understanding telomere biology has been
      enormous, and understanding has rapidly transferred to human telomere research.
      Most work using model organisms to study telomerase and nontelomerase-based
      telomere-maintenance systems has centered on yeasts, ciliates, and insects. But
      it is now timely to put considerably more effort into plant models for a number
      of reasons: (i) the rice and Arabidopsis genome sequencing projects make data
      mining possible; (ii) extensive collections of insertion mutants of Arabidopsis
      thaliana enable phenotypic effects of protein gene knockouts to be analyzed,
      including for those genes involved in telomere structure, function (including,
      for example, in meiosis), and maintenance; and (iii) the variability of plant
      telomeres is considerable and ranges from the telomerase-mediated synthesis of
      the Arabidopsis-type (TTTAGGG) and vertebrate-type (TTAGGG) repeats to sequences
      synthesized by telomerase-independent mechanism(s) that are still to be
      discovered. Here we describe how the understanding of telomere biology has been
      advanced by methods used to isolate telomeric sequences and prove that the
      putative sequences isolated are indeed telomeric. We show how assays designed to
      prove the activity of telomerase [e.g., telomeric repeat amplification protocol
      (TRAP)] lead not only to an understanding of telomere structure and function, but
      also to the understanding of cell activity in development and in the cell cycle.
      We review how assays designed to reveal protein/protein and protein/nucleic acid
      interactions promote understanding of the structure and activities of plant
      telomeres. Together, the data are making significant contributions to telomere
      biology in general and could have medical implications.

PMID- 15727131
TI  - Generation of long tracts of disease-associated DNA repeats.
AB  - The generation of long uninterrupted DNA repeats is important for the study of
      repeat instability associated with several human genetic diseases, including
      myotonic dystrophy type 1. However, obtaining defined lengths of long repeats in
      vitro has been problematic. Strand slippage and/or DNA secondary structure
      formation may prevent efficient ligation. For example, a purified
      (CTG)140.(CAG)140 repeat fragment containing 4-bp AGCA/TGCT overhanging ends
      ligated poorly using T4 or Escherichia coli DNA ligase, although limited repeat
      ligation occurred using thermostable DNA ligase. Here we describe a general
      procedure for ligating multimers of DNA repeats. Multimers are efficiently
      ligated when slippage is prevented or when DNA repeats contain a single G/C
      overhang. A cloning vector is designed from which pure repeat fragments
      containing a G/C overhang can be generated for further ligation. (CAG)n.(CTG)n
      DNA molecules longer than 800 bp were generated using this approach. This
      approach also worked for (GAA)n.(TTC)n, (CCTG)n-(CAGG)n, and (ATTCT)n.(AGAAT)n
      tracts associated with Friedreich ataxia, DM2, and spinocerebellar ataxia type
      10, respectively.

PMID- 15727132
TI  - Incorporation of reporter-labeled nucleotides by DNA polymerases.
AB  - The incorporation of fluorescently labeled nucleotides into DNA by DNA
      polymerases has been used extensively for tagging genes and for labeling DNA.
      However, we lack studies comparing polymerase efficiencies for incorporating
      different fluorescently labeled nucleotides. We analyzed the incorporation of
      fluorescent deoxynucleoside triphosphates by 10 different DNA polymerases,
      representing a cross-section of DNA polymerases from families A, B, and reverse
      transcriptase. The substitution of one or more different reporter-labeled
      nucleotides for the cognate nucleotides was initially investigated by using an in
      vitro polymerase extension filter-binding assay with natural DNA as a template.
      Further analysis on longer DNA fragments containing one or more nucleotide
      analogs was performed using a newly developed extension cut assay. The results
      indicate that incorporation of fluorescent nucleotides is dependent on the DNA
      polymerase, fluorophore, linker between the nucleotide and the fluorophore, and
      position for attachment of the linker and the cognate nucleotide. Of the
      polymerases tested, Taq and Vent exo DNA polymerases were most efficient at
      incorporating a variety of fluorescently labeled nucleotides. This study suggests
      that it should be feasible to copy DNA with reactions mixtures that contain all
      four fluorescently labeled nucleotides allowing for high-density labeling of DNA.

PMID- 15727133
TI  - Mini chamber system for long-term maintenance and observation of cultured cells.
AB  - We constructed a mini chamber system that was able to maintain cell culture on a
      microscope for long periods. It is a modified closed system with medium perfusion
      and CO2 circulation. The closed CO2 circulation and ample air inside the chamber
      distinguish it from other closed systems. Using different cell lines, the system
      was shown to be able to support long-term, time-lapse recording. After 229 hours
      of time-lapse recording, A2058 cells (a melanoma cell line) became overconfluent
      but still multiplied. Many CAD cells (a murine neuron-like cell line) still moved
      their cell bodies and kept their neurite-like processes after 28 days of
      recording. The entire healing process of a scratch-wounded 124 (a bladder cancer
      cell line) monolayer can be monitored. Such a modified closed system should find
      many applications in developmental biology, cell biology, and cancer biology
      where long-term, time-lapse recording is required or when the health of cells is
      important.

PMID- 15727134
TI  - MEGO: gene functional module expression based on gene ontology.
AB  - Existing analysis tools to study the collective properties of gene functional
      modules cannot return highly homogeneous modules and do not provide quantitative
      measures of module activity level. By partitioning genes according to multiple
      gene functional categorization principles and summarizing gene expression values
      into module expression values, MEGO (module expression based on gene ontology), a
      standalone microarray data analysis program, is able to extract highly activated
      gene functional modules that are of much interest to microarray experimenters.
      With multiple functional categorization principles simultaneously introduced in
      MEGO, the partition of genes is more delicate, and the collective property of a
      group of genes is sharpened and easier to capture. The quantitative measures of
      module activity levels returned by MEGO give users a quick impression of the
      direction and degree of module regulation. MEGO efficiently determines the
      answers to frequently asked questions, such as which functional classes have been
      induced or repressed under a specific experiment and to which levels these
      functional classes have been affected. MEGO is available free of charge for
      academic use and may be downloaded from http://www.dxy.cn/mego/MEGOInstall.EXE.
      Supplementary information can be found on the authors' web page at
      http://www.dxy.cn/mego/ and at the BioTechniques' web site at http://www.
      BioTechniques.com/February2005/TuSupplementary.html.

PMID- 15727135
TI  - Improved real-time RT-PCR method for high-throughput measurements using second
      derivative calculation and double correction.
AB  - Quantification of mRNA expression levels using real-time reverse transcription
      PCR (RT-PCR) is increasingly used to validate results of DNA microarrays or
      GeneChips. It requires an improved method that is more robust and more suitable
      for high-throughput measurements. In this report, we compare a user non-influent,
      second derivative method with that of a user influent, fit point method that is
      widely used in the literature. We also describe the advantage of using a double
      correction: one correction using the expression levels of a housekeeping gene of
      an experiment as an internal standard and a second using reference expression
      levels of the same housekeeping gene in the tissue or cells. The first correction
      permits one to decrease errors due to sample preparation and handling, while the
      second correction permits one to avoid the variation of the results with the
      variability of housekeeping in each tissue, especially in experiments using
      various treatments. The data indicate that the real-time PCR method is highly
      efficient with an efficiency coefficient close to the theoretical value of two.
      The results also show that the second derivative method is more accurate than the
      fit point method in quantifying low gene expression levels. Using triplicate
      experiments, we show that measurement variations using our method are low with a
      mean of variation coefficients of <1%.

PMID- 15727136
TI  - Overexpression of multi-heme C-type cytochromes.

PMID- 15727137
TI  - Efficient micro-recovery and guanidination of peptides directly from MALDI target
      spots.
AB  - A method is presented for the recovery and subsequent guanidination of tryptic
      peptides from samples previously spotted on a matrix-assisted laser
      desorption/ionization (MALDI) target. The procedure is shown to have
      applicability to both in-solution and in-gel digests, yielding improved
      confidence in protein identification and sequence coverage in all instances.
      Recovery from the plate is essentially quantitative, with no residual analyte
      observed on the target spot. The technique is rapid, simple, and has extended
      applicability to other processing steps, including (but not limited to)
      derivatization for specific peptide studies or enzymatic treatment for subsequent
      profiling of posttranslational modifications. This method circumvents the failure
      of an initial analysis to generate suitable information and is particularly
      relevant for the analysis of precious samples.

PMID- 15727138
TI  - [Tetracyclines: progress of fundamental research].

PMID- 15727140
TI  - [In vitro antiviral activity of fullerene amino acid derivatives in
      cytomegalovirus infection].
AB  - The in vitro effect of 5 water soluble fullerene C60 amino acid derivatives (FAD)
      on the development of cytomegalovirus infection was studied in the schemes of the
      therapeutic, prophylactic and virucidal action. The following compounds as FAD
      were used: fullerene conjugated with Na salt of gamma-aminobutyric acid (C60-ABA
      Na), 2 derivatives based on Na salts of fullerene-gamma-aminobutyric acid and
      fullerene-omega-caproic acid (C60-ABA-OH-Na and C60-ACA-OH-Na respectively) and 2
      derivatives based on methyl ethers of the above mentioned fullerene amino acids
      (C60-ABA-OH-CH3 and C60-ACA-OH-CH3). All the FAD were able to inhibit the
      development of the virus cytopathogenic action in the cell culture. However, the
      compounds had different antiviral properties. C60-ABA-OH-Na, C60-ABA-CH3 and C60
      ACA-CH3 showed marked antiviral activity in the prophylactic scheme. 50-Percent
      inhibition of the virus cytopathogenic action (ID50) was observed when
      concentrations of the compounds were 0.31, 5 and 25 mcg/ml respectively. C60-ACA
      OH-Na inhibited the development of cytomegalovirus infection in the cell culture
      only in the scheme of the therapeutic action (ID50 4 mcg/ml). C60-ABA-Na had the
      highest antiviral effect. In a concentration of 0.22 mcg/ml it inhibited the
      cytomegalovirus plague-forming capacity by 50% in both the prophylactic and the
      virucidal schemes. The chemotherapeutic index of the compound was within the
      limits of 2500 to 5450.

PMID- 15727139
TI  - [Screening of natural compounds with hypolipidemic activity].
AB  - In the screening programme for natural hypolipidemic compounds 702 strains of
      soil microorganisms were tested and 25 of them were selected because of their
      ability to produce compounds inhibiting sterol synthesis in Hep G2 hepatoma
      cells. The compounds were estimated in the microbiological model with
      Tolypocladium inflatum 106 as the test microbe. The 2nd stage of the screening
      resulted in isolation of 13 strains producing compounds with high hypolipidemic
      activity, analogous to or higher than the activity of lovastatin in the
      experimental models.

PMID- 15727141
TI  - [Immunomodulating, antioxidant and hepatoprotective effects of immobilized dosage
      forms of rifampicin and cephalexin].
AB  - The aim of the study was to lower the immunosuppressory, prooxidant and
      hepatotoxic effects of rifampicin and cephalexin by their immobilization in
      erythrocyte vehicles. The experiments were performed on Wistar rats with the use
      of rifampicin, cephalexin and lysozyme (ZAO Ferane) and hemodes (6% aqueous
      saline solution of low molecular polyvinylpyrrolidone, mol. wt. 12600+/-2700).
      Rifampicin- and cephalexin-entrapped erythrocytes were prepared.
      Spectrophotometric procedures for quantitative assay of the immobilized
      antibiotics were developed. The impact of the solution concentration and
      incubation time on the level of the antibiotic entrapping was studied. The
      erythrocyte vehicles were shown to be able to entrap the antibiotics for 9 days
      and to preserve their stability for 24 hours. It was observed that the increase
      of the immunosuppressory, prooxidant and hepatotoxic effects of the antibiotics
      administered without the vehicles to the laboratory animals infected by
      staphylococci was dose-dependent. The use of the antibiotics entrapped in the
      erythrocyte vehicles stimulated the immune reactivity of the animals and
      normalized the indices of lipid peroxidation, the antioxidant system, cytolysis
      and cholestasis.

PMID- 15727143
TI  - [Biological characterization of Bifidobacterium and Lactobacillus preparations
      made with the use of hydrolysate-milk and hydrolysate-soybean media].
AB  - A complex of biological characteristics important for design of the therapeutic
      and prophylactic activities of Bifidobacterium and Lactobacillus preparations
      made with the use of hydrolysate-milk and hydrolysate-soybean media was
      comparatively estimated. The use of the hydrolysate-soybean medium resulted in an
      increase of the antagonistic activity of the preparations against a number of
      opportunistic pathogens that was not connected with changing of their acidity and
      the content of lysozyme, a bacteriolytic enzyme in the culture fluid. The change
      in the cultivation conditions due to substitution of the hydrolysate-milk medium
      for the hydrolysate-soybean medium stimulated the adhesive capacity of the
      production strains used in the study, which was especially evident with respect
      to the representatives of the genus Bifidobacterium.

PMID- 15727142
TI  - [Preparations for serodiagnosis of diseases due to causative agents of ixode tick
      borne Borreliosis (Lyme disease). Communication 2. Comparative study of
      recombinant enzyme immunoassay test-systems (rELISA) for serological diagnosis of
      ixode tick-borne Borreliosis].
AB  - One foreign and two Russian recombinant enzyme immunoassay test-systems were
      comparatively investigated under conditions of an encoded experiment. Sensitivity
      in the experiment with the Russian test-systems Borreliosis-ELISA-IgG and Lyme
      Best was 63.8 and 68.8% respectively. As for the test-system Borrelia IgG
      Recombinant, it was 47.5%. All the test-systems were highly specific (94.4 to
      99.5%). The test-systems Lyme Best and Borrelia IgG Recombinant revealed partial
      cross reactions with sera from patients with systemic lupus erythematosus and
      leptospirosis.

PMID- 15727144
TI  - [Efficacy and safety of azithromycin prophylaxis of respiratory tract infections
      in military community].
AB  - The efficacy and safety of azithromycin prophylaxis of community-acquired
      pneumonia (CAP) in young adults in a military training centre of the Ministry of
      Defence of the Russian Federation located in the Central European Region of
      Russia were studied. Two prophylactic regimens with azithromycin vs. the control
      were evaluated: azithromycin, 500 mg/w for 8 weeks (R1), azithromycin, 1500 mg
      once upon the enrolment (R2) and no drugs (R3). Nasopharyngeal carriage of
      Streptococcuspneumoniae and its susceptibility to antibacterials were estimated
      thrice: before the exposure, after the exposure within the 9th week and after the
      exposure within the 20th week. The MLS(B) phenotype was suspected when the
      isolates were resistant to erythromycin and clindamycin. During the observation
      period of 22 weeks CAP was diagnosed in 20.2% of 678 subjects in group R3, 8.6%
      of 508 subjects in group R1 (Risk Ratio =0.4, 95% Cl = 0.3-0.6) and 10.3% of 507
      subjects in group R2 (Risk Ratio = 0.5, 95% Cl = 0.4-0.7). The S.pneumoniae
      carriage rate at visit 0 was 34-35%, within the 9th week it was 75, 66 and 50%
      (p<0.05) in groups R1, R2 and R3 respectively, and within the 20th week it was
      69, 57 and 36% in the same groups (p<0.05). At visit 0 no macrolide resistance
      was detected in any of the 40 isolates tested. The background level of
      intermediate penicillin resistance was revealed in 0-14% of the isolates.
      Dramatic growth of macrolide resistance was observed within the 9th week in group
      R1 (95.7%, 44 resistant strains, Azithro+Clinda resistance in 37% of them) and in
      group R2 (89.5%, 34 resistant strains, Azithro+Clinda resistance in 11.9% of
      them). By the 20th week the resistance rate decreased up to 40 % (16 resistant
      strains, Azithro+Clinda resistance in 10% of them) in group R1 and up to 22.6% (7
      resistant strains, Azithro+Clinda resistance in 5.4% of them) in group R2. As for
      penicillin resistance, no unfavourable shifts were detected. The study
      demonstrated the effectiveness of the azithromycin prophylaxis of CAP in healthy
      young men at high transient risk of the disease, as well as the possible risk for
      selection of resistant endemic pathogens.

PMID- 15727145
TI  - [Moraxella catarrhalis in chronic and relapsing respiratory tract infections in
      children].
AB  - Examination of 700 children with chronic and relapsing respiratory tract
      infections showed that during the period from 1996 to 2003 Moraxella catarrhalis
      strains were isolated from the sputum of 5.5-9.7% of the patients. The frequency
      of the emergence was the third after Haemophilus influenzae and Streptococcus
      pneumoniae. In healthy children M. catarrhalis was isolated in 2.7% of the cases.
      The most frequent detection of M. catarrhalis was stated in children under 1 year
      (4.5%). The antibiotic susceptibility tests revealed that the majority of the M.
      catarrhalis isolates had beta-lactamase activity, were resistant to
      benzylpenicillin, ampicillin and lincomycin and highly susceptible to
      amoxycillin/clavulanate, macrolides, certain cephalosporins and levofloxacin. The
      isolates were most frequent in the patients of the rather severe contingent
      (congenital lung disease, alveolitis, chronic pneumonia, bronchial asthma). In
      such patients the bronchoobstructive syndrome was more frequent (46.6%). High
      frequency of the affection of the upper respiratory tracts in the examined
      children was stated (62.1%).

PMID- 15727146
TI  - [Imipenem and cefepime in empirical therapy of infectious complications after
      radical surgeries in patients with invasive cancer of the urinary bladder].
AB  - Urinary tract injection (UTI) is one of the main causes of severe complications
      and death in oncologic patients and particularly in patients with invasive cancer
      of the urinary bladder. In our Clinic an up-to-date system for infection control
      recording all cases of UTI in oncologic patients is being exploited since 2001.
      The paper presents the data on our observations during the period from 2001 to
      2003 concerning typical UTI in patients with invasive cancer of the urinary
      bladder, etiological agents of UTI and their susceptibility to a wide range of
      antibacterials, including imipenem and cefepime, a 4th generation cephalosporin,
      used for adequate therapy of UTI in oncourologic patients.

PMID- 15727147
TI  - [Prophylaxis of fungal infection in patients with hematologic neoplasms and
      severe neutropenia after high-dose chemotherapy].
AB  - Infection is one of the main causes of death in patients with hemoblastoses.
      Within the last years there was observed an increase in the ratio of fungal
      infections in the structure of mortality among hematologic patients with
      neutropenia. The present study was aimed at comparative estimation of the
      efficacy of the prophylactic use of various azole antifungal agents in patients
      with hematologic neoplasms and severe neutropenia. The trial enrolled 88 patients
      comparable by the diagnosis and chemotherapy characteristics, in whom severe
      neutropenia developed after intensive therapy. Antifungal drugs were used
      prophylactically when the neutrophil count lowered below 1.0 x 10(9)/l until its
      increasing above 1.0 x 10(9)/l or when the signs of fungal infection were
      evident. Itraconazole was used in cyclodextrin solution in 30 patients in a dose
      of 0.2 g orally twice a day and fluconazole was used in capsules in 24 patients
      in a dose of 0.2 g orally once a day. The results were compared with those of the
      ketoconazole use in a dose of 0.2 g orally twice a day (n = 34). The frequency of
      fungal infection proved by the clinical documentation was 20.5% in the
      ketoconazole group (k) (7 out of 34 patients), 8.3% in the fluconazole group (f)
      (2 out of 24 patients) and 6.6% in the itraconazole group (i) (2 out of 30
      patients), p (k-f) = 0.21, p (k-i) = 0.11 and p (f-i) = 0.74. The frequency of
      fungal infection proved by the microbiological documentation was statistically
      much higher in the ketoconazole group (38.2%) vs. the fluconazole group (8.3%) (p
      = 0.013) and the itraconazole group (6.6%) (p = 0.004). The prophylactic use of
      itraconazole and fluconazole was efficient in preventing development of invasive
      mycoses in the patients with hemoblastoses and severe neutropenia. Their efficacy
      was much higher than that of ketoconazole.

PMID- 15727148
TI  - [Modern fluoroquinolones (ciprofoxacin, levofloxacin) and the treatment of skin
      and soft tissue infections].

PMID- 15727150
TI  - Microbiological degradation of pentane by immobilized cells of Arthrobacter sp.
AB  - The increasing production of several plastics such as expanded polystyrene,
      widely used as packaging and building materials, has caused the release of
      considerable amounts of pentane employed as an expanding agent. Today many
      microorganisms are used to degrade hydrocarbons in order to minimize
      contamination caused by several industrial activities. The aim of our work was to
      identify a suitable microorganism to degrade pentane. We focused our attention on
      a strain of Arthrobacter sp. which in a shake-flask culture produced 95%
      degradation of a 10% mixture of pentane in a minimal medium after 42 days of
      incubation at 20 degrees C. Arthrobacter sp. cells were immobilized on a
      macroporous polystyrene particle matrix that provides a promising novel support
      for cell immobilization. The method involved culturing cells with the expanded
      polystyrene in shake-flasks, followed by in situ growth within the column.
      Scanning electron microscopy analysis showed extensive growth of Arthrobacter sp.
      on the polymeric surface. The immobilized microorganism was able to actively
      degrade a 10% mixture of pentane, allowing us to obtain a bioconversion yield of
      90% after 36 h. Moreover, in repeated-batch operations, immobilized Arthrobacter
      sp. cells were able to maintain 85-95% pentane degradation during a 2 month
      period. Our results suggest that this type of bioreactor could be used in pentane
      environmental decontamination.

PMID- 15727151
TI  - Changes in soil microbial community composition induced by cometabolism of
      toluene and trichloroethylene.
AB  - The effects of trichloroethylene (TCE) on microbial community composition were
      analyzed by reverse sample genome probing. Soil enrichments were incubated in
      dessicators containing an organic phase of either 1 or 10% (w/w) toluene in
      vacuum pump oil, delivering constant equilibrium aqueous concentrations of 16 and
      143 mg/l, respectively. Increasing the equilibrium aqueous concentration of TCE
      from 0 to 10 mg/l led to shifts in community composition at 16, but not at 143
      mg/l of toluene. In closed system co-degradation studies, TCE at an aqueous
      concentration of 1 mg/l was effectively degraded by toluene-degrading soil
      enrichments once the aqueous toluene concentration dropped below 25 mg/l. Little
      TCE degradation was observed at higher toluene concentrations (50-250 mg/l). The
      results indicate that TCE changes microbial community composition under
      conditions where it is being actively metabolized.

PMID- 15727152
TI  - Inhibition of bacterial perchlorate reduction by zero-valent iron.
AB  - Perchlorate was reduced by a mixed bacterial culture over a pH range of 7.0-8.9.
      Similar rates of perchlorate reduction were observed between pH 7.0 and 8.5,
      whereas significantly slower reduction occurred at pH 8.9. Addition of iron
      metal, Fe(0), to the mixed bacterial culture resulted in slower rates of
      perchlorate reduction. Negligible perchlorate reduction was observed under
      abiotic conditions with Fe(0) alone in a reduced anaerobic medium. The inhibition
      of perchlorate reduction observed in the presence of Fe(0) is in contrast to
      previous studies that have shown faster rates of contaminant reduction when
      bacteria and Fe(0) were combined compared to bacteria alone. The addition of
      Fe(0) resulted in a rise in pH, as well as precipitation of Fe minerals that
      appeared to encapsulate the bacterial cells. In experiments where pH was kept
      constant, the addition of Fe(0) still resulted in slower rates of perchlorate
      reduction suggesting that encapsulation of bacteria by Fe precipitates
      contributed to the inhibition of the bacterial activity independent of the effect
      of pH on bacteria. These results provide the first evidence linking accumulation
      of iron precipitates at the cell surface to inhibition of environmental
      contaminant degradation. Fe(0) was not a suitable amendment to stimulate
      perchlorate-degrading bacteria and the bacterial inhibition caused by
      precipitation of reduced Fe species may be important in other combined anaerobic
      bacterial-Fe(0) systems. Furthermore, the inhibition of bacterial activity by
      iron precipitation may have significant implications for the design of in situ
      bioremediation technologies for treatment of perchlorate plumes.

PMID- 15727153
TI  - Conversion of food waste into hydrogen by thermophilic acidogenesis.
AB  - Conversion of food waste into hydrogen by thermophilic acidogenesis was
      investigated as a function of organic loading rate (OLR), hydraulic retention
      time (HRT) and pH in a continuous stirred tank reactor. In order to identify
      hydrogen-producing microorganisms, denaturing gradient gel electrophoresis (DGGE)
      of the polymerase chain reaction (PCR)--amplified V3 region of 16S rDNA analysis
      was conducted at each tested pH. The conversion of food waste into hydrogen was
      strongly influenced by the operational conditions. The hydrogen production was
      increased as OLR increased up to 8 gVSl(-1) d(-1), but drastically decreased at
      10 gVSl(-1) d(-1). The yield of hydrogen was decreased from 2.2 to 1.0 mol-H2/mol
      hexose consumed as HRT decreased from 5 to 2 days. More carbohydrates in the food
      waste were decomposed at longer HRT, 76-90%, at HRT of 2-5 days. The hydrogen
      production peaked at pH 5.5+/-0.1 and significantly decreased at pH 5.0+/-0.1.
      The biogas produced was composed of hydrogen and carbon dioxide, but no methane
      was detected at all tested conditions. The hydrogen contents in the gas produced
      were more than 55% (v/v) and not sensitive to all tested conditions. The optimum
      operational condition for continuous hydrogen production from the food waste was
      obtained at 8 gVSl(-1)d(-1), 5 days HRT and pH 5.5+/-0.1 where the hydrogen
      production rate, content, yield and the efficiency of carbohydrate decomposition
      were 1.01 H2/l-d, 60.5% (v/v), 2.2 mol-H2/mol-hexose consumed and 90%,
      respectively. The hydrogen production was related with the concentration of total
      organic acids (TOA) which was strongly dependent on that of butyrate indicating
      that the reaction was mainly butyrate fermentation. The hydrogen-producing
      microorganism of Thermoanaerobacterium thermosaccharolyticum that involved in
      acetate/butyrate fermentation, was detected with strong intensity at all tested
      pHs by denaturing gradient gel electrophoresis (DGGE) of the polymerase chain
      reaction (PCR)--amplified V3 region of 16S rDNA analysis and sensitive to the
      tested pHs. The experimental results indicated that effective hydrogen production
      from the food waste could be obtained continuously by thermophilic acidogenesis
      at proper operational condition.

PMID- 15727154
TI  - Monitoring of petroleum hydrocarbon degradative potential of indigenous
      microorganisms in ozonated soil.
AB  - This study was performed to investigate the petroleum hydrocarbon (PH)
      degradative potential of indigenous microorganisms in ozonated soil to better
      develop combined pre-ozonation/bioremediation technology. Diesel-contaminated
      soils were ozonated for 0-900 min. PH and microbial concentrations in the soils
      decreased with increased ozonation time. The greatest reduction of total PH (TPH,
      47.6%) and aromatics (11.3%) was observed in 900-min ozonated soil. The number of
      total viable heterotrophic bacteria decreased by three orders of magnitude in the
      soil. Ozonated soils were incubated for 9 weeks for bioremediation. The number of
      microorganisms in the soils increased during the incubation period, as monitored
      by culture- and nonculture-based methods. The soils showed additional PH-removal
      during incubation, supporting the presence of PH-degraders in the soils. The
      highest removal (25.4%) of TPH was observed during the incubation of 180-min
      ozonated soil during the incubation while a negligible removal was shown in 900
      min ozonated soil. This negligible removal could be explained by the existence of
      relatively few or undetected PH-degraders in 900-min ozonated soil. After a 9
      week incubation of the ozonated soils, 180-min ozonated soil showed the lowest
      TPH concentration, suggesting that appropriate ozonation and indigenous
      microorganisms survived ozonation could enhance remediation of PH-contaminated
      soil. Microbial community composition in 9-week incubated soils revealed a slight
      difference between 900-min ozonated and unozonated soils, as analyzed by whole
      cell hybridization. Taken together, this study provided insight into indigenous
      microbial potential to degrade PH in ozonated soils.

PMID- 15727155
TI  - Effect of a commercial alcohol ethoxylate surfactant (C11-15E7) on biodegradation
      of phenanthrene in a saline water medium by Neptunomonas naphthovorans.
AB  - Biodegradation of poorly soluble polycyclic aromatic hydrocarbons (PAHs) has been
      a challenge in bioremediation. In recent years, surfactant-enhanced
      bioremediation of PAH contaminants has attracted great attention in research. In
      this study, biodegradation of phenanthrene as a model PAHs solubilized in saline
      micellar solutions of a biodegradable commercial alcohol ethoxylate nonionic
      surfactant was investigated. The critical micelle concentration (CMC) of the
      surfactant and its solubilization capacity for phenanthrene were examined in an
      artificial saline water medium, and a type of marine bacteria, Neptunomonas
      naphthovorans, was studied for the biodegradation of phenanthrene solubilized in
      the surfactant micellar solutions of the saline medium. It is found that the
      solubility of phenanthrene in the surfactant micellar solutions increased
      linearly with the surfactant concentrations, but, at a fixed phenanthrene
      concentration, the biodegradability of phenanthrene in the micellar solutions
      decreased with the increase of the surfactant concentrations. This was attributed
      to the reduced bioavailability of phenanthrene, due to its increased
      solubilization extent in the micellar phase and possibly lowered mass transfer
      rate from the micellar phase into the aqueous phase or into the bacterial cells.
      In addition, an inhibitory effect of the surfactant on the bacterial growth at
      high surfactant concentrations may also play a role. It is concluded that the
      surfactant largely enhanced the solubilization of phenanthrene in the saline
      water medium, but excess existence of the surfactant in the medium should be
      minimized or avoided for the biodegradation of phenanthrene by Neptunomonas
      naphthovorans.

PMID- 15727156
TI  - Characterization of different decomposition stages of biowaste using FT-IR
      spectroscopy and pyrolysis-field ionization mass spectrometry.
AB  - The decomposition stage and stabilization of organic matter in biowaste (mixture
      of yard waste and kitchen waste), originating from an open windrow process, were
      investigated using Fourier transform infrared (FT-IR) spectroscopy and pyrolysis
      field ionization mass spectrometry (Py-FIMS). These investigations provided
      detailed information about chemical constituents and their behavior during the
      composting process. The chemical compounds were classified by their molecular
      signals in Py-FIMS. Multivariate statistical analysis revealed, that during the
      composting process, the group containing lipids, fatty acids and other chemical
      compounds with aliphatic skeletons changed the most. Corresponding with Py-FIMS
      findings changes were observed in absorbance bands of infrared spectra that
      reflect this group of organic compounds: the aliphatic methylene bands at 2925
      and 2850 cm(-1), the band of C=O vibrations of carboxylates at 1640 cm(-1) , the
      O-H in-plane bend of carboxylic acids, the CO2 stretch of carboxylates and the
      CH2 group of alkanes at around 1430 cm(-1). During decomposition these bands
      decreased up to a steady level that indicated stabilization. The band at 1260
      1240 cm(-1) that can be assigned to the C--O stretch of carboxylic acids or to
      the C-N stretch of amides and the band of aromatic amines at 1320 cm(-1)
      disappeared completely. The nitrate band at 1384 cm(-1) appeared at a later stage
      of the composting process. The relative increase of chemical compounds like
      moieties of lignin, humic acids and tannins in the composted material contributed
      to the aromatic C=C band at around 1640 cm(-1).

PMID- 15727157
TI  - Evaluation of an integrated anaerobic/aerobic SBR system for the treatment of
      wool dyeing effluents. Purification of wool dyeing effluent in a SBR.
AB  - This work examined the performance of a sequencing batch reactor treating dyeing
      effluents from a factory that processes mainly wool and wool/polyester blends.
      Different operational conditions were evaluated, namely the influence of the
      anaerobic and the subsequent aerobic phase on the organic load removal, as well
      as the effect of the length of the aeration period (from 8 to 12 h) on process
      efficiency. A comparison between a fill stage in fast and slow modes was carried
      out. Results indicate that the cycle 2 conditions (fast fill and 12 h aeration
      time) improved the overall efficiency (85+/-6% soluble COD and 95+/-4% BOD5
      removal yields) with a predominant COD uptake occurring in the aerobic stage.
      Slow, linear COD removal was observed in the anaerobic phase, in contrast with an
      exponential COD decrease in the oxic phase. For SS a level under 100 mg/l was
      general achieved in the exit of the reactor. With respect to dye degradation, a
      noticeable decrease of the absorbance measured in the UV-visible range was
      observed. This could be explained by the reduction of the azo bonds of some of
      the present dyes in the anaerobic step, in which ORP values lower than -400 mV
      were attained. Some oxidation of anthraquinone sulphonate dyes and of the
      aromatic amines resulting from azo bond cleavage could also have been taken
      place, as well as bioelimination mechanisms such as dye sorption.

PMID- 15727158
TI  - Metabolic responses of microbiota to diesel fuel addition in vegetated soil.
AB  - The effects of trees and contamination on microbial metabolic activity,
      especially that of hydrocarbon degrading bacteria, were compared during
      phytoremediation to find which conditions increase diesel fuel removal. Diesel
      fuel utilisation, microbial extracellular enzyme activities and utilisation of
      Biolog ECO plate carbon sources by soil bacteria were determined during
      phytoremediation experiments consisting of two separate diesel applications.
      Diesel fuel removal after 28 days of second diesel application was 20-30% more
      than after the first application 1 year earlier. Soil microbiota utilised 26-31
      of the 31 Biolog ECO plate carbon sources. Carbon source utilisation profiles
      indicated minor differences in microbiota in soil vegetated with pine compared to
      microbiota in soil vegetated with poplar. The potential maximum rates of
      aminopeptidase activity were 10-10(2) microM AMC/h/g dry soil prior to and after
      second diesel application, except 14 days after the second diesel addition, where
      the rates were at the scale of 10(3) microM AMC/h/g dry soil. The potential
      maximum rates of esterase activity were 10(3)-10(4) microM MUF/h/g dry soil. The
      presence of plants did not influence the activity of esterases. The utilisation
      of diesel by soil bacteria in Biolog MT2 plate assay was higher in contaminated
      soil, especially when vegetated, than in uncontaminated soil, measured both as
      lag times and maximum specific utilisation rates. MT2 plate assay detected the
      biological response after diesel fuel addition better than general activity
      methods.

PMID- 15727159
TI  - [Mechanism of action of xipamide and its classification as a "low ceiling
      diuretic". Pharmacodynamic-pharmacokinetic studies in healthy volunteers and in
      kidney and liver patients].
AB  - Xipamide (CAS 14293-44-8) shows structural features comparable with the thiazide-
      as well as the class of loop diuretics. According to earlier findings this
      diuretic, in contrast to the thiazides, should not decrease the glomerular
      filtration rate (GFR) and be effective even in patients with advanced renal
      failure. Therefore recently the question, which class of diuretics xipamide
      should be related to, has been increasingly discussed. In order to solve this
      issue, the diuretic effect of xipamide was assessed in healthy volunteers once
      without and once under strict water and salt restriction. Additionally, changes
      in GFR were monitored by means of measurement of the creatinine clearance.
      Kinetic parameters were determined in plasma and urine; further, in patients with
      liver cirrhosis, renal elimination kinetics of the diuretic were correlated with
      the concentration of direct plasma bilirubin, as a marker of cholestasis, at the
      beginning of a treatment with xipamide, 40 mg qd. The investigations proved that
      xipamide, like a typical thiazide diuretic, gives rise to a temporary decrease in
      GFR of about 30 %, provided the renin-angiotensin-aldosterone system of the
      volunteer is activated by previous salt and water restriction. Xipamide leads to
      an increase of K+ and Mg2+ excretion, but to a decrease of Ca2+ excretion in
      urine, a charactaristical feature of the thiazide-like diuretics. The correlation
      between Na+ excretion and drug excreted in urine over time showed a functional
      graph that is characteristic for a "low ceiling" thiazide diuretic. In patients
      with renal failure FE(Na) was increased when related to the GFR-adjusted drug
      excretion rate, whereas it was diminished in conditions with decreased effective
      circulating volume like in liver cirrhosis with ascites. It could be shown that
      the elimination kinetics of xipamide are determined by renal drug clearance,
      which proportionally decreases with GFR. In patients with liver failure, a
      decrease of non-renal drug clearance went along with an increase in urinary drug
      excretion. The amount of drug excreted in urine (Ae) proportionally increased
      with the concentration of the patients' direct plasma bilirubin. Thus, from a
      pharmacological as well as clinical point of view xipamide acts like a thiazide
      diuretic. As could be shown for other thiazides some time ago, xipamide is
      effective not only in patients with cardiovascular diseases, but also in those
      with advanced renal failure.

PMID- 15727160
TI  - Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin
      and the flavonoids quercetin and isorhamnetin following single and multiple oral
      dosing of a hypericum extract containing tablet.
AB  - The objective of these two open phase I clinical trials was the investigation of
      the bioavailability of five constituents from a hypericum extract containing
      tablet, which are discussed as the components contributing to the antidepressant
      action. Each trial included 18 healthy male volunteers who received the test
      preparation, containing 612 mg dry extract of St John's wort (STW-3, Laif 600),
      either as a single oral dose or as a multiple once daily dose over a period of 14
      days. Concentration/time curves were determined for hypericin, pseudohypericin,
      hyperforin, the flavonoid aglycone quercetin, and its methylated form
      isorhamnetin for 48 h after single dosing and for 24 h on day 14 at the end of 2
      weeks of continuous daily dosing. After single dose intake, the key
      pharmacokinetic parameters were determined as follows: hypericin: area under the
      curve (AUC(0-infinity)) = 75.96 h x ng/ml, maximum plasma concentration (Cmax) =
      3.14 ng/ml, time to reach Cmax (t(max)) = 8.1 h, and elimination half-life (t1/2)
      = 23.76 h; pseudohypericin: AUC(0-infinity) = 93.03 h x ng/ml, Cmax = 8.50 ng/ml,
      t(max) = 3.0 h, t1/2 = 25.39 h; hyperforin: AUC(0-max) = 1009.0 h x ng/ml, Cmax =
      83.5 nglml, t(max) = 4.4 h, t1/2 = 19.64 h. Quercetin and isohamnetin showed two
      peaks of maximum plasma concentration separated by about 4 h. Quercetin: AUC(0
      infinity) = 318,7 h x ng/ml, Cmax (1) = 47.7 ng/ml, t(max) (1) = 1.17 h, Cmax (2)
      = 43.8 ng/ml, t(max) (2) = 5.47 h, t1/2 = 4.16 h; isorhamnetin: AUC(0-infinity) =
      98.0 h x ng/ml, Cmax (1) = 7.6 ng/ml, t(max) (1) = 1.53 h, Cmax (2) = 9.0 ng/ml,
      t(max), (2) = 6.42 h, t1/2 = 4.45 h. Under steady state conditions reached during
      multiple dose administration similar results were obtained. Further
      pharmacokinetic characteristics calculated from the obtained data were the mean
      residence time (MRT), the lag-time, the peak-trough fluctuation (PTF), the lowest
      observed plasma concentration (Cmin), and the average plasma concentration (Cav).
      The data obtained for hypericin, pseudohypericin and hyperforin generally
      corresponded well with values previously published, with some deviations observed
      for the extent of absorption of hypericin and the time course of absorption and
      elimination of hyperforin. The kinetic characteristics of the hypericum
      flavonoids are reported here for the first time. The trial preparation was well
      tolerated.

PMID- 15727161
TI  - Treatment of vertigo with a homeopathic complex remedy compared with usual
      treatments: a meta-analysis of clinical trials.
AB  - The increasing interest in alternative medical practices has led to a number of
      controlled studies on herbal and homeopathic agents. This paper presents the
      results of a meta-analysis of four recent clinical trials evaluating the
      homeopathic preparation Vertigoheel (VH) compared with usual therapies
      (betahistine, Ginkgo biloba extract, dimenhydrinate) for vertigo in a total of
      1388 patients. Two trials were observational studies and the other two were
      randomised double-blind controlled trials. The duration of treatment (6-8 weeks)
      and dosage were comparable in all studies. Treatments were evaluated for the
      variables "number of vertigo episodes", "intensity of episodes" and "duration of
      episodes". As the studies differed in the age of patients and in the baseline
      values of vertigo, the individual reductions of number, intensity and duration of
      episodes were adjusted on equal age and baseline values (total means). An
      analysis of variance (with studies as random effects) showed no relevant
      influence of studies on the adjusted reductions and no relevant interaction
      between studies and treatment effects. The meta-analysis of all four trials
      showed equivalent reductions with VH and with control treatment: mean reduction
      of the number of daily episodes 4.0 for VH and 3.9 for control (standard error
      0.11 for both groups); mean reduction of the duration (on a scale 0-4) for VH 1.1
      and for the control 1.0 (standard error 0.03 for both groups); mean reduction of
      the intensity (on a scale 0-4) for VH 1.18 and for the control 1.8 (standard
      error 0.03 for both groups). In the non-inferiority analysis from all trials, VH
      was non-inferior in all variables. The results show the applicability of meta
      analyses on the data from studies with homeopathicdrugs and support the results
      from the individual studies indicating good efficacy and tolerability of VH in
      patients with vertigo.

PMID- 15727162
TI  - Evaluation and standardisation of the antioxidant properties of two Indian
      remedies with biochemical test assays.
AB  - Two drugs composed of several different plant extracts are in use in Ayurvedic
      medicine for the treatment of asthma and arthritis, respectively. There is
      increasing evidence that reactive oxygen species (ROS) arising from several
      enzymatic reactions are mediators of inflammatory events such as the above
      mentioned. Plant extracts have the potential for scavenging such reactive oxygen
      species, dependent on the individual test system. Using biochemical model
      reactions relevant for the formation of ROS in vivo at inflammatory sites,
      inhibition of the indicator reaction for the formation of ROS is thought to
      represent a potential mechanism of the physiological activity of the
      corresponding preparation.

PMID- 15727163
TI  - Safety and efficacy of the long-term adjuvant treatment of primary intermediate-
      to high-risk malignant melanoma (UICC/AJCC stage II and III) with a standardized
      fermented European mistletoe (Viscum album L.) extract. Results from a
      multicenter, comparative, epidemiological cohort study in Germany and
      Switzerland.
AB  - BACKGROUND: Mistletoe therapy is the most frequently used complementary treatment
      in cancer patients in Germany and Switzerland. However, its safety and efficacy
      were controversially discussed, also in case of malignant melanoma (MM).
      OBJECTIVES: The present study should evaluate the therapeutic safety and efficacy
      of a long-term therapy with a standardized fermented European mistletoe (Viscum
      album L.) extract Iscador (FME) during post-surgical aftercare of primary
      intermediate to high-risk MM (UICC/AJCC stage II-III) patients and compare it
      with an untreated parallel control group from the same cohort. METHODS: The study
      was designed as a multicenter, comparative, retrolective, epidemiological cohort
      study with parallel groups, carried out according to the guidelines of Good
      Epidemiological Practice (GEP). All patients suffered from surgically treated and
      histopathologically confirmed primary MM in UICC/AJCC stage II-III without
      distant metastases. In the study group, FME was administered subcutaneously 2-3
      times weekly for at least three months, while the untreated control group was
      merely observed ("watchful waiting"). In both groups some patients also received
      radio-, chemo-, and/or immunotherapy. The patients were followed until the last
      visit or until death. Unselected, chronologically ordered, and standardized
      anonymous data from medical records that satisfied the predefined eligibility
      criteria were included for the "per protocol" analysis. Safety was assessed by
      the number of patients with FME-associated adverse drug reactions (ADRs) and by
      the search for tumor enhancement. The primary endpoint of efficacy was the
      adjusted tumor-related survival. Secondary end-points were the overall-, the
      disease-free- and the brain metastasis-free survival. The survival results were
      analyzed after adjustment for baseline imbalances, treatment regimens and other
      potential confounders by the Cox proportional hazard regression method. RESULTS:
      686 eligible patients (329 FME vs. 357 controls) from 35 centers were observed
      for a median aftercare of 81 vs. 52 months. The median FME therapy duration was
      30 months. At baseline, both groups were comparable concerning demography, tumor
      history and risk factors for progression. Additional adjuvant chemotherapy was
      more frequent in the study group, while immunotherapy was more frequent in the
      control group. Eleven patients (3.3 %) developed systemic ADRs attributed to the
      FME-treatment, and 42 patients (12.8 %) developed local ADRs, with mild to
      intermediate (WHO/CTC grade 1-2) ADR severity and spontaneous resolution in most
      cases. In six patients the ADRs resulted in therapy termination. Life-threatening
      ADRs, ADR-related mortality or tumor enhancement were not observed. On the
      contrary, the incidence rate of lung metastases and the adjusted hazard ratio for
      brain metastases were significantly lower in the FME group. In the course of the
      study and during aftercare a total of 212 (30.9 %) patients relapsed or
      progressed, and 107 (15.6 %) died. A significantly longer tumor-related survival
      was found in the FME group when compared with the untreated controls (unadjusted
      tumor-related mortality rate 8.9 % vs. 10.7 %, Kaplan-Meier estimate, Log-rank
      test, p = 0.017), which was confirmed after adjusting for potential confounders
      by the tumor-related mortality hazard ratio estimate HR (95 % confidence
      intervals) = 0.41 (0.23-0.71), p = 0.002. The adjusted HR results of the overall
      survival, disease-free survival, and the brain metastases-free survival were also
      significantly superior in the FME group. CONCLUSION: The long-term FME treatment
      in patients with primary intermediate to high-risk MM appears safe. Tumor
      enhancement was not observed. When compared with an untreated parallel control
      group from the same cohort, the results of the FME treatment suggested a
      significant survival benefit in primary stage II-III MM patients. These results
      on survival warrant reconfirmation in a prospective randomized clinical trial
      with optimized study design and treatment conditions.

PMID- 15727164
TI  - Antileukemic activity and cellular metabolism of the aryl phosphate derivative of
      bromo-methoxy zidovudine (compound WHI-07).
AB  - The novel aryl phosphate derivative of bromo-methoxy zidovudine (ZDV/AZT)
      (compound WHI-07, CAS 213982-96-8) was found to be a potent antileukemic agent
      against human leukemia, lymphoma, and multiple myeloma cell lines in MTT and
      clonogenic assays with low micromolar IC50 values. In addition, WHI-07 was
      antimitotic, leading to cell fusion and developmental arrest in the Zebrafish
      model of rapid cell proliferation. WHI-07 was cytotoxic to drug-sensitive (NALM
      6, MOLT-3, HL-60, P388) and multi-drug resistant (MDR) leukemia cell lines (HL
      60/VCR, HL-60/ADR, P388/ ADR). Treatment of leukemia cells with WHI-07 showed
      rapid and dramatic depletion of all cellular nucleoside diphosphate and
      triphosphate (NDP/NTP) pools, which would contribute to the overall reduction of
      nucleic acid synthesis and cell death. WHI-07 was rapidly metabolized to alaninyl
      ZDV monophosphate (Ala-ZDV-MP), the levels of which inversely correlated with
      cytotoxic IC50 values of WHI-07. Glutathione was found to mediate the in vitro
      and in vivo detoxification pathway of WHI-07 to 3'-azidothymidine-5'-p
      bromophenylmethoxyalaninyl phosphate and Ala-ZDV-MP, respectively. The proposed
      intracellular metabolic pathway for WHI-07 involves a thiol-mediated
      dehalogenation step followed by the paraoxon-sensitive carboxylesterase-mediated
      reaction leading to the formation of Ala-ZDV-MP as the major intracellular
      metabolite.

PMID- 15727165
TI  - Evaluation of anti-herpetic and antioxidant activities, and cytotoxic and
      genotoxic effects of synthetic alkyl-esters of gallic acid.
AB  - The n-alkyl esters of gallic acid (CAS 13857-8) have a diverse range of uses as
      antioxidants in food, cosmetics and pharmaceutical industries. Pharmaceutical
      studies performed with these compounds have found that they have many therapeutic
      potentialities including anti-cancer, antiviral and antimicrobial properties.
      However, more interest has been devoted to their antioxidant activity due to the
      ability to scavenge and reduce reactive oxygen species (ROS) formation. In this
      study, gallic acid and 14 different alkyl gallates were tested. The cytotoxicity
      and anti-herpetic (HSV-1, KOS and 29-R strains) activity were studied by using
      the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)
      colorimetric assay and the cell viability by using the Trypan blue dye exclusion
      method. The genotoxicity was studied by the Comet assay and the antioxidant
      activity by using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging and
      microsomal lipid peroxidation-inhibiting activities. The results showed that all
      the tested compounds have anti-herpetic activity at non cytotoxic concentrations
      with selectivity indices (SI = CC50/EC50) varying from 0.89 to 18.34, depending
      on the used HSV-1 strain. It was observed that all tested alkyl gallates showed
      some degree of genotoxicity, at the tested concentrations, except cetyl gallate,
      at 256.60 micromol/L (p <0.05, t-Student test), probably induced by ROS released
      by infected cells and/or by the alkyl gallates that were not antioxidants, at the
      tested concentrations, in which they demonstrated anti-herpetic activity. The
      hydroxyl groups can induce DNA damage due interactions with some metal ions,
      which are naturally present in the culture medium supplemented with fetal bovine
      serum, probably explaining the genotoxicity detected. However, the obtained
      results showed considerable antioxidant activity at smaller concentrations, when
      compared to quercetin which is considered as a reference drug due to its already
      described antioxidant potential: DPPH radical scavenging activity with IC50
      values varying from 17 to 31 micromol/L; and microsomal lipid peroxidation
      inhibiting activity with IC50 values varying from 21 to 59 micromol/L. It was
      observed that the presence of hydroxyl groups in these molecules is important for
      their pharmacological profile, but the length of the lateral carbonic chain does
      not have considerable influence.

PMID- 15727166
TI  - [Therapeutic effects of rhEPO, rhG-CSF on sulfur mustard induced toxicity in
      dogs].
AB  - OBJECTIVE: To evaluate the therapeutic effects of recombinant human
      erythropoietin (rhEPO) and recombinant human granulocyte colony stimulating
      factor (rhG-CSF) on sulfur mustard (SM) induced toxicity in dogs. METHODS: Ten
      dogs were used as the animal model. Control group had four dogs while treatment
      group had six. Half an hour after subcutaneously injected with 12 mg/kg (body
      weight) of SM, the dogs of the treatment group were treated by rhEPO, rhG-CSF and
      other medicines. General examinations of blood were measured before injecting SM
      and were continually watched for a week after poisoning. RESULTS: Three dogs in
      control group died in three days after poisoning, dogs in treatment group all
      survived. WBC of the control group decreased significantly 3 days after
      poisoning. RBC of the control group had a slight increase at first, then came
      down. While WBC and RBC of treatment group remained constant. LYM of both groups
      descended notably right after poisoning, especially in control group. Two days
      after poisoning, RC in treatment group began to rise and remained at high level
      for about a week. No obvious changes of RC in control group were found.
      CONCLUSION: The use of rhEPO and rhG-CSF after SM exposure can stimulate the
      growth of the erythrocyte, reticulocyte and leucocyte in dogs. Therefore, rhEPO
      and rhG-CSF may be significant assistant drugs in future experiment of SM.

PMID- 15727167
TI  - [Gene expression differences between the anti-BPDE-transformed and normal cells
      by suppression subtractive hybridization].
AB  - OBJECTIVE: To screen the gene expression differences between the BPDE-transformed
      and normal cells. METHODS: Suppression subtractive hybridization was performed to
      profile differentially expressed genes between BPDE and normal 16HBE cells. The
      BPDE-transformed cells was used as tester, and the normal cells as driver. The
      nested PCR products were inserted into TA vector after two subtractive
      hybridization and two PCR. The clones were picked up randomly and analyzed with
      PCR. Dot blot was used to test the same source with the tester. The overexpressed
      cDNA fragments in BPDE cells were sequenced and compared with known genes in
      Genbank. RESULTS: Seven genes were identified being overexpressed in BPDE
      transformed cells: translation elongation factor 1 alpha 1, mitochondrion gene,
      solute carrier family 25, EphA2, tyrosine 3-monooxygenase/tryptophan 5
      monooxygenase activation protein, lactate dehydrogenase A (LDHA), tripartite
      motif-containing 28 (TRIM28), etc. One fragment could not be found in the known
      genes, it could be found in the EST database. CONCLUSION: These over-expressed
      genes may be related to the carcinogenesis of BPDE, in addition, one unknown gene
      may be responsible for the malignant transforming effect of BPDE.

PMID- 15727168
TI  - [Protein changes in human embryonic lung fibroblasts after hydroquinone
      stimulation using proteomic technique].
AB  - OBJECTIVE: To explore the molecular mechanism of cell response induced by
      hydroquinone, we investigated the protein profile after treatment with
      hydroquinone in human embryonic lung fibroblasts. METHODS: After HQ treatment,
      cells were lysed in lysis solution, then the supernatant were collected and
      precipitated with acetone prior to protein concentration determination. The total
      cellular proteins were separated using two-dimensional gel electrophoresis and
      visualized by colloidal coomassie blue staining. Digital images were analyzed
      using Imagemaster 2.0 software. The differentially expressed protein spots were
      picked and digestion in gel then identified by peptide mass fingerprinting using
      MALDI-TOF. RESULTS: There were 15 protein spots changed after HQ stimulation.
      Among them 8 protein spots were identified by PMF including some oxidative stress
      and cytoskeleton related proteins. CONCLUSION: Protein profile was altered after
      HQ stimulation.

PMID- 15727169
TI  - [Study on genetic polymorphism of NQO1 and susceptibility to benzene poisoning].
AB  - OBJECTIVE: To explore the relationship between genetic polymorphism of NQO1 and
      susceptibility to benzene poisoning (BP). METHODS: The genetic polymorphism of
      NQO1 for 100 patients with benzene poisoning and 90 workers exposed to benzene
      who were engaged in the same working time and job title as patients with benzene
      poisoning were detected by PCR-RFLP. RESULTS: There was a 2.82-fold (95% CI: 1.42
      5.58 ) increased risk of BP in the subjects with NQO1 C609T mutation genotype
      (T/T) compared with those carrying heterozygous (C/T) and wild type (C/C), and
      there was a 2.94-fold (95% CI: 1.25-6.90) increased risk of BP in the subjects
      with NQO1 C609T mutation genotype (T/T) compared with those carrying wild type
      (C/C) . There was a trend that the risk of BP in subjects with NQO1 C609T
      mutation genotype (T/T) was higher than those carrying heterozygous (C/T) and
      even higher than those carrying wild type (C/C) (chi2(trend) = 6.01, P = 0.014).
      CONCLUSION: The subjects with NQO1 C609T mutation genotype (T/T) were more
      susceptive to benzene and NQO1 is as a biomarker to assessment the risk of
      benzene poisoning for individual.

PMID- 15727170
TI  - [Effects on the survival rates and damage on DNA of benzo[a]pyrene or lead alone
      or in combination in rat neurons in vivo].
AB  - OBJECTIVE: To study the effects on the survival rates and DNA damage of
      benzo[a]pyrene or lead alone or in combination in rat neurons in vivo. METHODS:
      Primary cultures of rat cerebellar neurons were prepared from 8-day-old pups, 10
      groups cultures in each experiments were used, (1) control group, (2) vehicle
      group (Equal volume of DMSO + S9-mix), (3) low dose lead group (PbAc 5
      micromol/L), (4) high dose lead group (PbAc 50 micromol/L), (5) low dose BaP
      group (BaP 5 micromol/L+ S9-mix), (6) high dose BaP group (BaP 50 micromol/L + S9
      mix), (7) low dose lead + low dose BaP group, (8) low dose lead + high dose BaP
      group, (9) high dose lead + low dose BaP group, (10) high dose lead + high dose
      BaP group. After 90 min administration, the neurons were collected by the method
      of trypsin digestion, the survival rates were detected by the method of Tapian
      blue dying, Detect cracks on the DNA straps by the method of SCGE. RESULTS: (1)
      The survival rates of all the administrated groups were significantly lower than
      that of control groups (P < 0.05, P < 0.01). (2) In the high-dose BaP group
      (group 6), groups combine administrated with BaP and lead, one or two of them at
      high dose (groups 8, 9, 10), the DNA damage were more serious than that of
      control groups (P < 0.01). CONCLUSION: (1) Both BaP and lead with some vivo
      neurotoxicity, the effects of two toxicants can do concord. (2) Neuron DNA damage
      may be one of the mechanisms by which BaP result in toxicity on the cultured
      neurons.

PMID- 15727171
TI  - [Apoptosis induced by cadmium and the expression of bcl-2 and p53 genes in LLC
      PK1 cells].
AB  - OBJECTIVE: To study the effect of cadmium on the apoptosis of porcine renal
      proximal tubule epithelial cells (LLC-PK1) and the relationships between the
      apoptosis and gene expression of the bcl-2 and mutant p53 (mtp53) protein.
      METHODS: Apoptotic bodies were examined by electron microscopy, the rates of
      apoptosis were measured by flow cytometry (FCM) and DNA ladder was detected by
      DNA gel electrophoresis. The expressions of bcl-2 and mtp53 were measured
      respectively by FCM. RESULTS: The apoptotic bodies of LLC-PK1 cells treated with
      CdCl2 at dose of 40 micromol/L for 12 h were observed by electron microscopy and
      the apoptosis rates of LLC-PK1 cells were 32.61%, which were higher than those of
      the control group (P < 0.01). Apparent DNA ladder was showed by DNA gel
      electrophoresis. LLC-PK1 cells were incubated with CdCl2 at doses of 0, 10, 20,
      40 micromol/L for 4 h or 8 h, it was found that expressions of bcl-2 and mtp53
      were decreased and where a significant dose-response was found (r = -0.910 for
      bcl-2 8 h, r = -0.716, -0.972 for mtp53 4 h, 8 h, respectively). CONCLUSION: The
      results were suggested that the apoptosis of LLC-PK1 cells induced by cadmium
      might be associated with the inhibitions of the expression of bcl-2 and p53.

PMID- 15727172
TI  - [Toxicity of manganese exposure on the postnatal development of dopaminergic
      neurons of nigra substance in rat brain].
AB  - OBJECTIVE: To study the poisonous effect of manganese on the postnatal
      development of dopaminergic neurons of nigra substance in rat brain. METHODS:
      Morris Water Maze was carried out to examine the muscle motor ability of the rat.
      Fluorometry was used to determine the dopamine levels of caudate nucleus.
      Immunochemistry combined with digital imagine analysis was carried out to observe
      the TH reactivity and its average densities of the TH-positive products in nigra
      substance and caudate nucleus respectively. RESULTS: (1) The latency to reach the
      platform above water in Morris Water Maze was longer and longer with the
      increasing of Mn-dose exposured. (2) The DA levels of the caudate nucleus, and
      the TH-immunochemical reactivity as well as the average densities of TH-positive
      products in nigra substance and caudate was significantly declined respectively
      with increasing of Mn-dose exposure. CONCLUSION: The postnatal development of
      dopaminergic neurons in nigra substance of the rat brain was damaged by manganese
      exposure, and the positive relationship existed between the damage effects and
      the Mn-dose exposure.

PMID- 15727173
TI  - [Effects of p,p'-DDE on intracellular MAPK pathway of rat Sertoli cells in
      vitro].
AB  - OBJECTIVE: To study effects of p,p'-DDE on intracellular p-ERK of rat Sertoli
      cells in vitro. METHODS: We cultured Sertoli cells separated from testicular
      tissue of rats and examined the changes of intracellular p-ERK, using
      immunohistochemical SABC method. RESULTS: It was showed that intracellular p-ERK
      increased with the dose of p,p'-DDE and had a dose-dependent trend. CONCLUSION:
      The results suggested that p,p'-DDE could result in the phosphorylation of ERK
      and induce the activation of the downstream road and the transcription and
      expression of genes.

PMID- 15727174
TI  - [Neuroprotection of lithium and the antagonism of lithium to toxic effects of
      lead on primary culturing cerebrocortical neurons in vitro].
AB  - OBJECTIVE: To investigate the toxic effects of lead on nervous system and the
      neuroprotection of lithium, we observed the impact of different dose of lead on
      the growth and survival of primary cultured cerebrocortical neurons, and the
      antagonism of lithium to lead. METHODS: We established the technique of primary
      culturing cerebrocortical neurons of newborn rats with serum-free medium. We
      observed the growth and survival of neurons treated with different dose of lead
      and 5 mmol/L lithium chloride through microscope, and measured the length of
      neuritis, we also compared the cell viabilities by MTT reduction assay. RESULTS:
      Lead could limit the growth of neurons, shorten the neuritis, and decrease the
      neurons viability (P < 0.01). Lithium chloride (5 mmol/L) had significant
      protective action on the neurons treated with lead. The length of neuritis were
      longer than that of the groups treated only with lead (10(-6) mol/L and 10(-5)
      mmol/L) (P < 0.01), and the neurons viability was also higher than that of groups
      treated with lead (10(-8)-10(-5) mol/L) (P < 0.01). CONCLUSION: Lead had the
      toxic effects on neurons, and lithium could protect the neurons against the
      toxicity of lead.

PMID- 15727175
TI  - [Arrested proliferation and molecular mechanism of MAPKs' activations in
      manganese-treated PC12 cell line].
AB  - OBJECTIVE: We employed a model in vitro that used PC12 cell line to test the
      concentration and time dependent relationship of Mn-treatment as well as the
      characteristics of MAPKs pathway under the same conditions, to explore the
      Neurotoxicity mechanisms of manganese. METHODS: PC12 cells in logarithm period
      incubated in culture media of 200, 400, 600, 800 micromol/L manganese (MnCl2) for
      1 day, 2 days, 3 days, 4 days respectively. The neurotoxic concentration of
      manganese (MnCl2) on PC12 cells was screened by MTT and Plate clone forming
      tests. Cell growth curve was made in Typan-blue dying experiment. Western-blot
      was used to test p-Erk1/2 and p-p38. RESULTS: MTT and plate clone tests showed
      that 200, 400, 600, 800 micromol/L MnCl2 could suppress the proliferation of PC12
      cells in dose and time-dependent trend during 1 d, 2 d, 3 d, 4 d respectively.
      The cell inhibited ratio on the fourth day in 600 micromol/L MnCl2 culture medium
      approached 50% or more. Western-blot tests showed that p-Erk2 of PC12 cells
      incubated in 600 micromol/L MnCl2 culture medium was decreasing gradually on the
      1st, 2nd, 3rd and 4th day and on the 2nd day less than control group by 75% (n =
      3, P < 0.05). With cells treated by 200, 400, 600 micromol/L MnCl2 for 4 days, p
      Erk2 lost by degrees. On the 4th day, p-Erk2 of 400 micromol/L MnCl2-treated
      group was less 78% than that of control group (n = 3, P < 0.05). P-p38 of PC12
      cells incubated in 600 micromol/L MnCl2 culture medium was increasing gradually
      on the 1st, 2nd, 3rd and 4th day and on the 3rd day 6.6 times higher than that of
      control group (n = 3, P < 0.05). P-p38 of PC12 cells enhanced by degrees in 200,
      400, 600 micromol/L MnCl2 treated for 4 days and in 400 micromol/L MnCl2 treated
      group on the 4th day was 4.7 times higher than that of control group (n = 3, P <
      0.05). CONCLUSION: The decreased p-Erk2 and the increased p-p38 maybe co-worked
      to induce proliferation arrest and apoptosis in PC12 cells.

PMID- 15727176
TI  - [Effect of selenium on liver type I deiodinase in iodine-excess mice].
AB  - OBJECTIVE: To investigate the effect of selenium on the activities of liver type
      I deiodinase (IDI) in iodine-excess mice. METHODS: Forty female weanling Balb/c
      mice of 18-22 body weight were randomly divided into 5 groups: normal control
      group (N, deionized water), iodine-excess group I (IE I, 3 mg/L Iodine water), IE
      I + Se group (+ 1 mg/L Se water), iodine-excess group II (IE II, 5 mg/L Iodine
      water) and IE II + Se group (+ 1 mg/L Se water), and they were fed with standard
      diets and different level of iodine and selenium water for 12 weeks. RESULTS:
      Iodine-excess groups show diffused colloid goiter; Serum TT4 of two iodine-excess
      groups were significantly higher than Normal control, and TT3 of IE II decreased
      significantly; The selenium level and IDI activity of mice liver was decreased
      significantly in iodine-excess group, but no difference between IE I and IE II.
      CONCLUSION: Iodine-excess intake can decrease the selenium level and IDI activity
      of mice liver, which maybe is the reason to increase the serum TT4 level and lead
      to goiter, and selenium can alleviate that.

PMID- 15727177
TI  - [Bioavailabilities of manganese sources based on heart manganese-containing
      superoxide dismutase gene expression for broilers].
AB  - OBJECTIVE: Two experiments were conducted to determine whether heart manganese
      containing superoxide dismutase (MnSOD) gene expression could detect the
      differences in bioavailabilities of Mn sources more quickly, sensitively and
      constantly than other indices. METHODS: In experiment 1, a total of 546 day-old
      commercial male Arbor Acres (AA) broilers were randomly assign to each of
      thirteen treatments with six cage replicates according to a completely randomized
      design involving a 4 x 4 factorial arrangement. Each group of birds was fed Mn
      unsupplemented corn-soybean meal basal diets (Control) or basal diets
      supplemented with 60, 120 or 180 mg/kg Mn as either Mn sulfate, Mn-Met E, Mn-AA B
      or Mn-AA C for 21 days. At 21 days of age, three birds from each cage were
      selected according to average bodyweight of the cage and killed. Heart and left
      leg were excised immediately. Mn concentrations in tissues, MnSOD activity and
      gene expression of MnSOD in heart were analyzed. In experiment 2, two hundred and
      seventy day-old AA commercial male broilers were randomly allotted to one of five
      treatments with six cage replicates in a completely randomized design, and fed a
      Mn-unsupplemented corn-soybean meal basal diet (Control) or the basal diet
      supplemented with 120 mg/kg Mn as each of the four Mn sources in experiment 1 for
      21 days. The methods in experiment 1 were used to select and slaughter birds from
      each cage on the 7th, 14th or 21st day. The tissues were collected and analyzed
      as well. RESULTS: (1) In experiment 1, ash Mn content, heart Mn content, and
      MnSOD activity in heart mitochondria on the 21st day were affected (P = 0.0001)
      by dietary added Mn level. Based on slope ratios from multiple linear regressions
      of these three indices on dietary added Mn intake, the relative bioavailabilities
      of organic Mn sources did not differ from that of MnSO4 (P > 0.14). Heart MoSOD
      mRNA level on the 21st day was affected by both Mn source (P < 0.10) and Mn level
      (P = 0.0001). Based on slope ratios from the multiple linear regression of heart
      MnSOD mRNA level on dietary added Mn intake, if 100% was set for Mn sulfate, the
      relative bioavailabilities of organic Mn sources with weak, moderate, and strong
      chelation strengths were 99.0%, 132.3% and 112.7%, respectively. The organic Mn
      source with the moderate chelation strength was more available (P < 0.05) than Mn
      sulfate and organic Mn sources with the weak or strong chelation strengths; (2)
      In experiment 2, the seven day-old chicks fed on the diet supplemented with the
      organic Mn source with the moderate chelation strength showed a higher (P < 0.02)
      MnSOD mRNA level than those fed on the diets supplemented with Mn sulfate and the
      organic Mn source with the weak chelation strength, and the same tendency was
      observed on the 14th day or 21st day (P < 0.05). Ash Mn content and heart MnSOD
      activity were less sensitive in detecting the differences among Mn sources in
      bioavailability than MnSOD mRNA level. CONCLUSION: The results indicate that
      dietary Mn significantly affected heart MnSOD gene expression pretranslationally,
      and heart MnSOD mRNA level as early as on the 7th day could detect differences in
      bioavailabilities of Mn sources more quickly, sensitively and constantly than all
      other indices. There was a close correlativity between chelation strengths of
      these organic Mn sources and their relative bioavailabilities for broilers, in
      which the organic Mn source with the moderate chelation strength was the most
      available. The estimation of relative bioavailabilities of Mn sources based on
      heart MnSOD mRNA level could request a shorter time of experimental period and
      smaller number of animals, and thus could be a new method for a quick and
      effective assessment in bioassays of Mn sources for broilers.

PMID- 15727178
TI  - [Putative mechanism of experimental immunological liver injury and influence of
      iron low-load on the injury in rat].
AB  - OBJECTIVE: To investigate the effects of superoxide dismutase (SOD) and reducing
      iron load on experimental immunological liver injury in rat. METHODS: 48 male
      Wistar rats were divided into six groups randomly. The animal model of iron low
      load was created by intravasation of deferoxamine (DFO) or phlebotomy
      respectively. Immunological liver damage model was reproduced by injection of
      lipopolysaccharide (LPS) and BCG (Bacilli Calmette Guerin). The following
      parameters were determined such as serum iron (SI), transferrin (TRF)
      concentration, total proteins (TP) volume, the serum activities of aspartate
      aminotransferase (AST), and malondialdehyde (MDA) content, the activities of
      superoxide dismutase and iron deposition (HIC) in liver tissue extracts. RESULTS:
      In comparison with blank control group, the SI levels lowered (P < 0.05) in pure
      DFO group, pure phlebotomy group and liver injury group. Compared with each own
      control groups, the serum activities of AST in all injury groups augmented and
      the levels of TP in them reduced significantly. The increased magnitude of the
      activities of AST and the decreased magnitude of TP levels in DFO injury group
      and phlebotomy injury group were less than those of pure injury group (P < 0.05).
      In comparison with the control group, the MDA levels in pure DFO and phlebotomy
      groups declined significantly and the activities of SOD in them had no
      significant difference. Compared with each own control groups, the MDA levels
      augmented and the activities of SOD reduced significantly in all injury groups.
      CONCLUSION: SOD activity reduces in immunological liver injury in rat. Iron low
      load can mitigate the severity of liver injury.

PMID- 15727179
TI  - [Molecular mechanism of cleft palate induced by retinoic acid].
AB  - OBJECTIVE: To explore the molecular mechanism of cleft palate induced by
      chemicals. METHODS: Retinoic acid was used as a known teratogen to induce cleft
      palate in ICR mice and a suppression subtractive hybridization (SSH) technique
      was applied to identify differentially expressed genes that related to cleft
      palate of ICR mice. RESULTS: 14 reverse differently and 9 forward differentially
      expressed clones were obtained. Some clones were selected to be sequenced and
      aligned to GenBank. CONCLUSION: In this study, suppressed Gpc3 and Insulin
      Induced protein 1 could affect growth of palate shelves and resulted in cleft
      palate by reducing the size of the palate shelves. Down-regulation of Ptprs
      interfered with a cell signal pathway and down-regulation of Tn C inhibited the
      cell de-adhesion and expression of Egfr, then suppressed Egfr prevented the
      normal expression of MMPs that influenced the medial edge epithelium disruption
      and caused cleft palate. Tn C could bind to Ptprs and Gpcs, and HSPGs were
      ligands for Ptrps. Up-regulate of Rps25 might play a role in cleft palate by
      excessively apoptosis.

PMID- 15727180
TI  - [Trend of seasonal change on intake of nutrients in a year of the residents in
      both northern and southern China].
AB  - OBJECTIVE: To study the change of intake of nutrients in a year, and determine
      whether there is any change of intake of nutrition according to different seasons
      of the people in both northern and southern China. METHODS: The method of 24-hour
      diet history recall was used to study about 300 healthy adults in three areas, a
      rural area in the northern and rural plus urban areas in the southern. The study
      was carried out once per two month, and each time last 3 days. Based on the
      amount of food intake, the amount of both nutrition and energy per person and per
      day was calculated. RESULTS: The amount of energy, protein, carbohydrate, fat
      intake of the residents in three areas was adequate. There was almost no
      significant difference of intake of energy and three major nutrients (protein,
      fat and carbohydrate) both in the southern and northern part of China among
      different seasons, as well as the seasonal intake of thiamin, riboflavin, vitamin
      E, niacin, and zinc. While the difference of intake of retinol (microg RE),
      ascorbic acid, potassium and calcium were significant among different seasons.
      CONCLUSION: This study showed that, in rural areas, any dietary survey should
      avoid January and July, which is either slack or busy season for farmers. In
      urban areas, any time of a year should not influence the results of a dietary
      survey.

PMID- 15727181
TI  - [Preparation and component analysis of tea pigments].
AB  - OBJECTIVE: To prepare tea pigments. METHODS: Tea pigments are prepared by solvent
      extraction from Sri lanka black tea. RESULTS: Tea pigments contains the
      components as follows: caffeine 1.77%, epigallocatechin 1.37%, catechin 1.20%,
      epicatechin 9.55%, epigallocatechin gallate 10.52%, epicatechin gallate 9.94%,
      theaflavin 10.34%, theaflavin monogallate 9.57%, theaflavin digallate 4.81%,
      thearubigin about 40.93%. CONCLUSION: The best proportions of the compound that
      are obtained with HPLC analysis.

PMID- 15727182
TI  - [Studies on comparing the toxicity between sodium selenite and selenomethionine
      in rats].
AB  - OBJECTIVE: To compare the toxicity between sodium selenite and selenomethionine
      (SeM) and to investigate the indicators of selenium toxicity. METHODS: Weanling
      Wistar rats of both sexes were randomly divided into seven groups, 14 rats each
      group. One group was fed basal diet and the others were fed basal diets
      containing 3, 6, 10 mg greater than that of SeM and female rats were more
      sensitive to excessive selenium than male rats. Se/kg added as sodium selenite or
      SeM for 12 weeks. RESULTS: Histopathological changes of the liver were observed
      in rats on Se 3 mg/kg diets while the decreasing of body weight occurred in rats
      on 6 Se mg/kg diet. Among the rats fed Se 6, 10 mg/kg diet, the body weight of
      rats in selenite-treated groups was lower than that of rats in SeM-treated
      groups. At the 3 or 6 mg/kg Se level, the rats fed SeM suffered slighter hepatic
      damage than those fed sodium selenite and in male rats slighter than female rats.
      The abnormal change of ratio of liver weight to body weight was found to be more
      obvious both in female rats and in selenite-treated rats. GPX activity in liver
      of female rats reduced with the increase of Se level in diets. However, GPX
      activity in RBC, plasma, kidneys and liver showed an ascending tendency with the
      increasing level of dietary Se. CONCLUSION: The minimum dose of intoxication of
      Se in diet may be around 3 mg/kg. The toxicity of selenite is greater than that
      of SeM and female rats were more sensitive to excessive selenium than male rats.

PMID- 15727183
TI  - [Established prolonged selenium deficiency of the SD rat animal model breed third
      generation in series].
AB  - OBJECTIVE: To establish selenium deficiency of the breed third generation SD rats
      animal model in series. METHODS: A Se-deficient diet mainly based on Se-deficient
      yeast. Groups of six female and six male SD rats original generation (F0) were
      fed on one of the five diets: (1) selenium- and iodine-adequate control group
      (Se+I+ group. Selenium: 0.1-0.3 microg/g, iodine > or = 0.2 microg/g), (2)
      selenium-deficient iodine-adequate group 1 (Se-I+ group. Selenium: 0.02 microg/g,
      iodine > or = 0.2 microg/g), (3) selenium-deficient iodine-adequate group 2 (Se
      I+ group2. Selenium: 0.005 microg/g, iodine > or = 0.2 microg/g), (4) selenium
      adequate iodine-deficient group (Se+I- group. Selenium: 0.1-0.3 microg/g, iodine:
      0.04 microg/g), (5) selenium- and iodine-deficient group (Se-I- group. Selenium:
      0.01 microg/g, iodine: 0.04 microg/g). Selenium-deficient iodine-adequate group2
      had been deled since generation 1 (F1). Serum Se and thyroid hormone
      concentrations, whole blood glutathione peroxidase (GSH-Px) activities, the
      weight, childbearing and livability were examined. RESULTS: There were durative
      lower Se concentrations in serum and lower GSH-Px activities in blood, and the
      weight, childbearing and livability reduced in Se- group and Se-I- group from F0
      to F3. CONCLUSION: We have established prolonged selenium deficiency of the SD
      rat animal model breed third generation in series successfully.

PMID- 15727184
TI  - [Study on the teratogenicity effects of genetically modified rice with Xa21 on
      rats].
AB  - OBJECTIVE: To observe the effects of genetically modified rice with Xa21 on the
      development of rat embryos. METHODS: According to sex, weanling rats were divided
      into four groups: transgenic rice group, non-transgenic rice group, AIN93G
      negative control group and MATDA positive control group. The rats were fed with
      corresponding food for 90 days and mated. The development of maternal rats and
      embryos were observed. RESULTS: The body weight gain of pregnant rats and the
      body weight, body length and tail length of fetal rats in transgenic rice group
      were significant increased than those in positive control group. The number of
      death embryos and adsorption embryos, the malformation rate (appearance, viscera,
      skeleton) in transgenic rice group were lower than those in positive control
      group. There were no significant difference of all indicators among transgenic
      rice group, non-transgenic rice group and AIN93G negative control group.
      CONCLUSION: Compared with the non-transgenic rice, transgenic rice modified with
      Xa21 gene showed no significant differences in rat pregnant rate and embryo
      development.

PMID- 15727186
TI  - [Multiplex PCR assay against E. coli O157 in foodstuffs].
AB  - A multiplex PCR assay for detection of Escherichia coli O157:H7 was developed
      with 4 pairs primers which focus on its specific fliC, rfbE, SLT I and SLT II
      genes. The target genes fragments of the PCR assay were 560 bp, 678 bp, 210 bp
      and 484 bp. The multiplex PCR had very high specificity to match all the 71
      tested strains including 58 E. coli strains and other 18 strains. The strain of
      E. coli O157:H7 was identified in one step, and the type of SLT was also
      identified as well. With the enrichment procedure, the strain of E. coli O157:H7
      were recovered at the detection limit of 0.1 cfu/ml from artificial inoculated
      pasteurized milk.

PMID- 15727185
TI  - [Determination of anti-nutrients in genetically modified crops].
AB  - OBJECTIVE: In order to assess the safety of genetically modified crops, the anti
      nutrients were determined in these novel crops and compared with their parental
      lines. METHODS: Five kinds of crops (rice, maize, soybean, cottonseed and
      rapeseed) from domestic and foreign companies were collected and the contents of
      anti-nutrients for each kind were analyzed. These anti-nutrients include phytate
      and protease-inhibitors (in rice, maize and soybean), gossypol (in cottonseed),
      glucosinolates and erucic acids (in rapeseed). RESULTS AND CONCLUSION: The
      contents of anti-nutrients in one type of maize, three types of rapeseeds and two
      types of cottonseeds didn't meet the requirement of "equivalence" in this study,
      but the finally conclusion should be made after many experimental data in the
      future.

PMID- 15727187
TI  - [Comparison of effect between multiplex and simplex nutritional intervention on
      hyperlipemia, hypertension or diabetes].
AB  - OBJECTIVE: To explore the effect of simplex and multiplex nutritional
      intervention on hyperlipemia, hypertension or diabetes. METHODS: 260 persons who
      have hyperlipemia were randomized to 3 groups: (1) "the multiplex nutritional
      intervention group", is given 100 g coarse food grain everyday and nutrition
      education, (2) "the simplex nutritional intervention group", is only given
      nutrition education, (3) "the control group". RESULTS: After three months, the
      degressive value of blood pressure, blood sugar and blood lipid respectively in
      the multiplex nutritional intervention group were larger than in the simplex
      nutritional intervention. CONCLUSION: There are better effect on hyperlipemia,
      hypertension and diabetes by nutrition education plus passive dietary
      intervention than by nutrition education.

PMID- 15727188
TI  - [Analysis on pneumoconiosis characteristic and its prediction in one coal mine].
AB  - OBJECTIVE: We aimed to investigate the characteristic of pneumoconiosis on coal
      miners and provide scientific evidences for its prevention. METHODS: To analyze
      the data of pneumoconiosis from one coal mine with the historical study and to
      predict its development tendency by the grey model of GM (1,1). RESULTS: (1) The
      year of work experience of pneumoconiosis (stage I) was 19.9 years and the age of
      its diagnosis (stage I) was 51.4 years. There was an obvious tendency that they
      became longer with years' back-shift. (2) During near forty years, the
      progression rates of pneumoconiosis from stage I to II and II to III were 13.6%
      and 11.2%, and the mean time was 8.3 and 8.1 years, respectively. It was obvious
      that the progression rate decreased gradually and the span prolonged with years'
      back-shift. (3) The complication rate of pneumoconiosis with lung tuberculosis
      was 12.5% and it increased with the progression of pneumoconiosis. The rate in
      dead cases was significantly higher than that in live cases (P < 0.01). (4) The
      sequence of death causes was pneumoconiosis (20.0%), lung tuberculosis (18.3%),
      chronic cor pulmonale (17.9%), and pulmonary carcinoma (9.0%), et al. (5) It was
      predicted that there would be 28 new cases every year during 2001-2020 years and
      the accumulated numbers of pneumoconiosis would be 2854 cases in 2020, but with a
      downward trends in the prevalence of -1.7%. CONCLUSION: It was suggested that the
      prevalence of pneumoconiosis should decrease obviously. However, it still remains
      a challenge about the task of effectively preventing and curing it or its
      complication.

PMID- 15727189
TI  - [Foodborne disease outbreaks in China from 1992 to 2001 national foodborne
      disease surveillance system].
AB  - OBJECTIVE: To study the foodborne disease outbreaks in the areas covered by
      National Foodborne Disease Surveillance System. METHODS: Total 13 provinces were
      included in the surveillance system, and the foodborne disease outbreaks data
      during 1992 to 2001 were collected. RESULTS: During 1992-2001, a total of 5770
      outbreaks of foodborne disease were reported. These outbreaks caused a reported
      162,995 persons to become ill. Among outbreaks for which the etiology was
      determined, bacterial pathogens caused the largest percentage of outbreaks
      (38.5%) and the largest percentage of cases (50.9%). Vibrio parahaemolyticus
      (31.1%) accounted for the largest number of outbreaks and cases. Chemical agents
      caused 37.5% of outbreaks and 28.6% of cases. CONCLUSION: More work needs to be
      done to improve the foodborne disease surveillance system.

PMID- 15727190
TI  - [Effects of high level Zn intake on metabolism in man].
AB  - OBJECTIVE: To observe the effects of high level Zn intake on zinc (Zn) copper
      (Cu), lipids metabolism and antioxidation function in man so as to provide
      scientific basis for Zn supplementation. METHODS: 40 rural healthy men were
      chosen and tablets of 50 mg Zn (as 0.2 g of zinc glucose) per day was taken by
      them for eight weeks. All subjects were checked up for five times: at week 0, 2,
      4, 8 during the period of Zn supplementation and at week 12 and their serum, RBC,
      hair, and 24h-urine were collected for assays at the same time. RESULTS: (1) Zn
      contents in serum, RBC and hair increased significantly after 2 to 4 weeks
      supplementation and decreased at 4 weeks after stopping supplementation, but they
      were still higher than those before supplementation. Zn contents in 24h-urine
      increased significantly after supplementation and decreased at 4 weeks after
      stopping supplementation to the same level as before supplementation. (2) Cu
      contents in serum, RBC and hair increased significantly after 4 weeks
      supplementation and decreased at 4 weeks after stopping supplementation. Cu
      contents in 24h-urine did not change significantly during experiment. (3) RBC
      superoxide dismutase (SOD) activities were decreased persistently after 2 weeks
      supplementation and were not recovered at 4 weeks after stopping supplementation.
      RBC glutathione peroxidase (GPX) activities increased significantly after 4 weeks
      supplementation. The content of lipid peroxide (LPO) increased significantly
      after 2 weeks supplementation. (4) Total cholesterol (TC), triglyceride (TG), Low
      density lipoprotein cholesterol (LDL-C) and apolipoprotein B100 (ApoB100)
      increased significantly, high density lipoprotein cholesterol (HLD-C) and
      apolipoprotein A1 (ApoA1) decreased after supplementation. CONCLUSION: When
      healthy men received 50 mg Zn supplement per day, it might interfere Zn, Cu and
      lipids metabolism and inhibit antioxidation process.

PMID- 15727191
TI  - [Intake of soy isoflavones and its correlation with prevalence of chronic
      diseases among rural women in Weichang County and Lanzhou City in China].
AB  - To evaluate the average intake of soy isoflavones and the correlation between
      this intake and prevalence of chronic diseases among Chinese rural women, soy
      food consumption and medical history of 1188 recruited rural adult women from
      Weichang County (Hebei Province) and Lanzhou City (Gansu Province) were collected
      using food frequency questionnaire. The results showed that the intake of soy
      isoflavones by Weichang and Lanzhou women was (15.3 +/- 18.9) mg/d (M = 8.8) and
      (19.5 +/- 32.9) mg/d (M = 10.1), respectively. There had statistically
      significant difference (P < 0.05). The distribution of soy isoflavones intake was
      skewed to the right. The reported disease prevalence in Weichang was 25.6% and
      higher than that in Lanzhou (18.8%). The average intake of soy isoflavones by
      healthy women was (17.8 +/- 22.8) mg/d (M = 9.5), which was higher than that by
      women who reported to have one of chronic diseases [(15.7 +/- 22.5) mg/d (M =
      8.3)] and significantly higher than that by women who reported to have
      cardiovascular diseases or chronic digestive system diseases (P < 0.05). These
      findings indicated an inverse correlation between soy isoflavones intakes and the
      prevalence of chronic diseases, suggesting that soy isoflavones may play a
      potential role in the prevention for chronic diseases.

PMID- 15727192
TI  - [Evaluating dietary quality of type 2 diabetics in Macao by Healthy Eating
      Index].
AB  - OBJECTIVE: To Evaluate dietary quality of type 2 diabetics in Macao with Healthy
      Eating Index and try to know whether the result from quantitative food frequency
      survey reflect the result from 24 hour recall dietary survey. METHODS: We
      randomly drew samples from file of registered type 2 diabetics on a Health Center
      of Macao. The diabetics have been investigated with both 24 hour dietary recall
      and quantitative food frequency dietary survey methods. According to the
      calculational method of healthy eating index, the result of dietary survey was
      transferred to Healthy Eating Index and evaluate the diet quality with it.
      RESULTS: There was a significant correlation between both results, including
      Healthy Eating Index, total energy and the percentages of energy from the three
      major nutrients, were obtained with 24 hour recall and quantitative food
      frequency. The Healthy Eating Index was 66.0. The minimum score of HEI components
      was milk. Total Energy of the diabetics was 5407.9 kJ (1287.6 kcal). And the
      percentages of energy from carbohydrate, total fat and protein were 59.4%, 25.8%
      and 16.1%, respectively. The intake of dietary fiber and calcium were 9.9 g and
      340 mg respectively. CONCLUSION: For this population, the results of both dietary
      survey methods can reflect each other well. According to the criteria of Healthy
      Eating Index, diet quality of 80% patients were among "need improvement". The
      situation of milk consumption was the worst. The consumption of fruits, grains
      and vegetable were too low and the consumption of sodium was too high. The
      percentages of energy from the three major nutrients were within the recommended
      range but the intake of total energy was too low. The intake of thiamin and
      riboflavin were not enough. Intake of dietary fiber and calcium were severely
      low.

PMID- 15727193
TI  - [Comparative study on different overweight reference applied on analyzing growth
      of Chinese children and adolescents].
AB  - The paper is studied based on anthropometry data collected in 1991 and 2000 in
      the China Health and Nutrition Survey, which is collaboration with the University
      of North Carolina at Chapel Hill. The sample are 7-18 years old children and
      adolescents. The primary purpose of this paper is to study the trends and
      prevalence of overweight and obesity among Chinese children and adolescents with
      different references and to compare the results and to further discuss their
      strengths and limits. The results from all the references indicate that
      overweight among Chinese children and adolescents are increasing sharply and
      becoming a problem that can't be overlooked. These references are not quite
      suitable for Chinese children and adolescents. Native age-sex-BMI references of
      overweight and obesity among Chinese children and adolescents should be
      established.

PMID- 15727194
TI  - [Study of preparation methods of polyclonal antibody of chymopapain].
AB  - OBJECTIVE: To study the preparation methods of polyclonal antibody of chymopapain
      with higher titre. METHODS: Three types of antigens-native chymopapain,
      chymopapain inactivated by H2O2 and inactivated by iodoacetic acid were injected
      into different male rabbits by hypodermic injections and by intravenous
      injection. The blood samples were obtained from veins in ear to test antisera
      after the 3rd injection, the used methods were Western blotting and ELISA. The
      data was analyzed by the SAS system. RESULTS: The antisera titre of two
      inactivated antigens were obviously higher than that of nature antigen (P <
      0.05), while there was no significant difference between the two inactivated
      antigens. Intravenous injection can obviously increase the ability of
      immunoresponse and raise antisera titre rapidly. CONCLUSION: The inactivated
      antigens have better immunogenicity than native chymopapain. As compared with
      iodoacetic acid, using H2O2 was an economical and effective method. The
      combination method of hypodermic injections and intravenous injection can raise
      antisera titre effectively and shorten the period of antibody preparation.

PMID- 15727195
TI  - [Determination of germanium in aloe vera by spectrophotometric method].
AB  - OBJECTIVE: To analyze the organic germanium in aloe vera from different
      localities. METHODS: The method was based on germanium forms a stable complex
      with phenylfluorone in the acidified solution and CTMAB as solubilization agent.
      The contents of the organic germanium in Aloe vera from different localities were
      determined by spectrophotometric methods. RESULTS: The linear range of
      determination is 0-0.7 microg/ml. The recovery is 98.1%-99.0% and the coefficient
      of variation is 1.8%.

PMID- 15727196
TI  - [Caco-2 cell monolayers and it's application in toxicological research].
AB  - Caco-2 cells derived from a human colon adenocarcinoma, spontaneously
      differentiate after reaching confluence in culture, exhibiting several
      morphological and functional characteristics of mature enterocytes. Caco-2 cell
      monolayers represents a well-established model for the study of intestinal
      transport of nutrients and xenobiotics, and is wildly used in pharmacology and
      toxicology. In this review the cell culture conditions, characteristics and
      functional parameters of model were introduced. The application of Caco-2 cell
      monolayers in studying mechanism, uptake, transport and gastrointestinal toxicity
      of xenobiotics were also explained.

PMID- 15727197
TI  - [Recent advances for research on effect of estrogen on immune system].
AB  - Estrogens exert indispensable effects on female reproductive organs but also on
      other target tissues including immune system. Studies showed that estrogens could
      regulate humoral and cellular immune. The change of levels and functions of
      estrogens may induce some autoimmune diseases. Further and deeper investigations
      are needed to study the relationships between estrogens and regulations of immune
      system, mechanisms and autoimmune diseases. It will benefit us to know the
      mechanisms of some autoimmune diseases related to estrogens and explore some new
      treatment strategies.

PMID- 15727198
TI  - [Progress on monoclonal antibody directed toward metal-chelate complexes and
      immunoassays to assess heavy metal contamination].
AB  - Heavy metals increase pollution on the environment. Recently, immunoassays was
      developed in convenience to practicability. The ELISAs and fluorescence
      polarization immunoassay (FPIA) based on preparation of monoclonal antibody
      (McAb) directed toward various heavy metal-chelate complexes may have great
      potential for application. Progress on McAb selective recognition metal-chelate
      complexes and immunoassays to assess heavy metal contaminations was reviewed in
      this paper.

PMID- 15727200
TI  - [Advanced progress on child nutrition and bone development].
AB  - The development to maturity of human bone has been achieved facing infants,
      childhood, adolescents and young adults, undergoing a long time and finally
      reaching the bone mass to the maximal peak. Recently, most of studies related to
      osteoporosis emphasized on increasing the peak bone mass attained from childhood
      or adolescence to young adult. The present paper reviews the factors influenced
      the peak bone mass, calcium status and bone development, the effect of milk
      consumption on bone mass and body growth and the prospects on the further studies
      in this field.

PMID- 15727199
TI  - [Progress on phage antibody library technology].
AB  - The exterior protein gene and the specific protein gene coded on the surface of
      phage can be fusedly expressed on the surface of phage with the recently
      developed technology-phage display technique. Through the PCR technique, the
      whole light chain genes and heavy chain genes can be amplified. Cloning these
      genes into lambda phage expression vectors and constructing phage antibody
      library through antigen adsorption-elution-proliferation, many targeting clones
      could be selected and the responding mono-clone antibody could be produced.
      Detailed progress in this regard was reviewed in the paper.

PMID- 15727201
TI  - [Tolerable upper intake level on vitamins and minerals].
AB  - According to the safety assessments of all vitamins and minerals intake
      undertaken by the US Institute of Medicine's Food and Nutrition Board (FNB), UK
      MAFF Expert Group on Safety and European Scientific Committee on Food, we are
      reviewing that the rationale of making ULs (the risk of experiencing adverse
      effects, assessment for dosage and reaction and Uncertainty Factors); comparing
      ULs of main vitamins and minerals between Chinese and American, and introducing
      new concepts of ULs on vitamin A, D, Ca, Cu, I, P, Se, Fe and V.

PMID- 15727202
TI  - [Research progress of the status of folate nutrition of different populations].
AB  - Folate is an essential nutrient of the B complex group of vitamins, as a
      cofactor, involving in numerous important intracellular reactions. The role of
      folate in human nutrition has become increasingly important with recent
      researches. While the relation between folate and anemia had been substantiated
      long ago, the difference of the folate nutritional status among populations and
      regions and the application of folate to preventing and curing anemia have not
      been definitely stated. However, scientists have always been active in detecting
      the status of folate nutrition of different populations and exploring practical,
      effective and scientific measures to prevent anemia for half a century. The
      surveillance for folate nutritional status and its application to preventing or
      curing anemia in recent years were summarized. In this article, it is suggested
      that the nutritional status of folate of the people at risk should be carefully
      monitored and effective measures be taken promptly in our country.

PMID- 15727203
TI  - [Knowing, liking and loving].

PMID- 15727204
TI  - [Microscopic mechanism of excitation-contraction coupling in cardiac myocytes].
AB  - Cardiac excitation-contraction coupling (ECC) is, in essence, a communication
      process between sarcolemmal voltage-dependent L-type calcium channels (LCCs) and
      ryanodine receptors (RyRs) of sarcoplasmic reticulum (SR) by the mechanism of
      calcium-induced calcium release (CICR). Recent advances displayed more
      information about the microscopic signaling between LCCs and RyRs. In calcium
      release couplons, the calcium influx through the opening of LCCs by membrane
      depolarization forms calcium sparklets locally which then act on the adjacent SR
      RyRs. Stochastic activation of RyRs discharges calcium sparks from different
      calcium couplons, which summate into global calcium transients. Therefore,
      ignition of calcium sparks by calcium sparklets constitutes the elementary events
      in ECC. This review focuses on the intermolecular signaling between LCCs and
      RyRs, to describe the microscopic view of CICR and ECC.

PMID- 15727205
TI  - [Progress in central interleukin-1 system and its signaling pathway].
AB  - Central interleukin-1 (IL-1 ) system is a relatively independent system which is
      composed of IL-1 and other molecules associated with IL-1 in functions or
      structures. The knowledge of central IL-1 system in the constitution and function
      have been extended with the discovery of new members and its function, the
      extensive and intensive research on intracellular signaling pathways, as well as
      the relationship among those molecules. This paper reviews the recent findings in
      the study of central IL-1 system, which comprises the new members, new signaling
      molecules, new biological functions, and the effects in the processes of
      physiology and pathophysiology.

PMID- 15727206
TI  - [Structure, function and modulation of actin-related protein 2/3 complex].
AB  - Microfilaments, composed of global actins, involve in many important
      physiological activities, such as the maintenance of cell shape and cell
      migration. Actin-related protein 2/3 ( Arp2/3) complex plays a key role in
      microfilament formation. Actin-related protein 2/3 ( Arp2/3 ) complex which is
      composed of seven different subunits is subjected to the modulation of many
      nucleation promoting factors (NPFs) and cooperates with these factors to regulate
      the actin nucleation. The study of the structure, function and modulation of
      Arp2/3 complex is important in understanding the mechanism of the formation of
      microfilament and the interaction between cytoskeleton and signaling molecules.

PMID- 15727207
TI  - [Inhibitory proteins against axon regeneration in the central nervous system].
AB  - Growth inhibition in the central nervous system (CNS) is a majar barrier to axon
      regeneration. To date, three inhibitory proteins of oligodendrocytes/myelin have
      been identified: myelin associated glycoprotein ( MAG) , Nogo-A and
      oligodendrocyte-myelin glycoprotein (OMgp). Recently, findings indicate that
      three distinct myelin components inhibit axon growth by binding a common
      receptor, the Nogo 66 receptor (NgR). These novel findings lead to further
      understanding of the barriers to axon regeneration after injury in the CNS and
      provide new avenues to explore the new theraphy strategy for the CNS injury.

PMID- 15727208
TI  - [The emergent role of p38 MAPKs in the regulation of cell cycle].
AB  - The p38 MAPKs are members of the MAPK family. Its pathway has been traditionally
      associated with the stress and immune response. More recently, it has been
      reported that the p38 MAPKs pathway can also regulate apoptosis and some
      differentiation process. It can regulate cellular growth and cell cycle
      checkpoints in different ways depending on the cell type and the stimulus.

PMID- 15727209
TI  - [Caveolae/caveolins and virus infection].
AB  - Caveolae, whose major structural proteins are Caveolins, are classically defined
      as flask-shaped plasma membrane invaginations with a characteristic diameter of
      50 to 100 nm. Caveolae/Caveolins play important roles in many physiological and
      pathological activities. In recent years, Caveolae/Caveolins were found to
      associate with the absorption, entry, trafficking, replication, assembly and
      budding for many viruses. This route helps break a new pathway to the
      exploitation of new antiviral drugs and the prevention and treatment of tumors.

PMID- 15727210
TI  - [Characteristics of ectopic discharges and their relationship with neuropathic
      pain].

PMID- 15727211
TI  - [The P2X3-containing receptors-mediated role in pain].

PMID- 15727212
TI  - [Expression and significance of estrogen receptors in the hypothalamic
      paraventricular nucleus].

PMID- 15727213
TI  - [Research on the regulation of the apoptosis in trophoblast].

PMID- 15727214
TI  - [In vitro spermatogenesis in mammalian].

PMID- 15727215
TI  - [The role of autophagy in cell death].

PMID- 15727216
TI  - [Advance in the research of anatomy and physiology of the medial geniculate
      body].

PMID- 15727217
TI  - [Recent progress in the studies of ferroportin 1].

PMID- 15727218
TI  - [Progress in the study of anti-oxidant peroxiredoxin family].

PMID- 15727219
TI  - [Receptor activator of NF-kappaB ligand and mammary development].

PMID- 15727220
TI  - [Homer and interacting synaptic proteins involved in glutamate receptor signal
      transduction].

PMID- 15727221
TI  - [Research progress in complexin].

PMID- 15727222
TI  - [Stochastic resonance and the roles of noise in sense neural firing].

PMID- 15727223
TI  - [Study on mice hepatitis virus].

PMID- 15727224
TI  - [The role of microwaves during cryopreservation of the biomaterials].

PMID- 15727225
TI  - Lessons from the neuropathology of atypical forms of multiple sclerosis.
AB  - Multiple sclerosis (MS) is characterized by multiple demyelinated inflammatory
      lesions disseminated in the central nervous system (CNS). Additional features of
      MS pathology include axonal loss and gliosis. Remyelination may take place
      predominantly in the early stages of lesion formation. Pathologically, important
      inter-individual differences have been observed with respect to oligodendrocyte
      preservation. Furthermore, different mechanisms of demyelination, such as T
      cell/macrophage-mediated demyelination, antibody/complement-mediated
      demyelination, and primary damage of the oligodendrocyte have been observed in
      individual MS patients. Atypical MS forms, such as Marburg's acute MS, Devic's
      neuromyelits optica, Balo's concentric sclerosis, and Schilder's diffuse
      sclerosis share key aspects of MS pathology, however, each of them harbors
      characteristic discriminative features. Devic's neuromyelitis optica may
      represent the prototypical disease with antibody/complement-mediated
      demyelination, whereas cases with Balo's concentric sclerosis show
      oligodendrocyte dystrophy. Acute disseminated encephalomyelitis (ADEM) may be
      regarded as a related condition lacking extensive demyelination. Thus, atypical
      MS forms may help to elucidate pathogenic mechanisms in MS.

PMID- 15727226
TI  - Atypical forms of multiple sclerosis or different phases of a same disease?
AB  - Multiple sclerosis (MS) patients complain with the first symptoms of the disease
      in a range period which varies from childhood to adult life. The extent to which
      clinical presentation, disease course and demographic features may differ between
      childhood and adult onset has been the object of investigation. This paper aims
      to demonstrate that the different clinical phenotypes in young and old patients
      might simply reflect different phases of a same pathological process.

PMID- 15727227
TI  - Multiple sclerosis in children under 10 years of age.
AB  - Despite the consistent amount of information accumulated in recent years on
      multiple sclerosis (MS) in childhood, many clinicians still view this condition
      as an exclusively young adult-onset disease and do not consider that it may occur
      and manifest even during infancy and pre-school age, suggesting that the number
      of MS cases in the paediatric age group may have been underestimated. Thus, the
      need to have practical parameters for therapeutic, counselling and educational
      purposes in such settings as caring for patients whose onset of disease is at
      very early ages may increasingly arise for practising clinicians. In addition,
      the clinical and radiographic criteria for the diagnosis of MS have not been
      validated in a paediatric MS population; accordingly, inclusion age at onset
      (such as for research purposes) is generally over 10 years. To highlight the
      peculiarities that characterise MS when it begins at this young age we have
      reviewed the literature and summarised our preliminary results with the national
      registry of the Italian Society of Paediatric Neurology (SINP) Study Group on
      Childhood MS in the group of MS patients with the earliest onset of disease
      (i.e., <10 years of age).

PMID- 15727228
TI  - Clinical characteristics of multiple sclerosis with early onset.
AB  - Clinical characteristics of multiple sclerosis with early onset are described.
      The evolution is frequently relapsing-remitting; compared to the adult form, the
      EDSS levels of 3, 4 and 6 are reached after a longer interval but at a lower age.
      Negative prognostic factors are: a short inter-attack interval, a high relapse
      rate, a relapsing-progressive course or the shift to the secondary progressive
      phase, and early accumulation of disability.

PMID- 15727229
TI  - Neuroradiology of multiple sclerosis in children.
AB  - Neuroimaging features of multiple sclerosis in children can differ from the usual
      adult pattern. Frequently, lesions can be more larger and pseudo-tumoral with a
      variable evolution. The most critical differential diagnosis in childhood is with
      acute disseminated encephalomyelitis that is a relatively frequent acquired
      inflammatory disease of the white matter with a polymorphous appearance. Some
      differences between multiple sclerosis and acute disseminated encephalomyelitis
      in children such as distribution of white matter lesions and frequency of gray
      matter involvement should be pointed out. Neveretheless only follow-up
      examination can make the definitive diagnosis in the majority of the cases.

PMID- 15727230
TI  - Diffusion tensor and magnetization transfer MR imaging of early-onset multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, demyelinating disease of the central
      nervous system (CNS) with the onset of symptoms typically occurring between the
      age of 20 and 40 years. However, in about 3% to 12% of the cases, the onset of
      the disease is before 16 years of age. This review summarizes the main results
      obtained by the application of conventional and non-conventional MRI techniques
      to the assessment of patients with early-onset MS, which showed that the overall
      amount of CNS damage in these subjects is mild, compared to that typically
      detected in the adult-form of the disease. This fits with the notion that an
      early onset of the disease is associated with a more favourable clinical
      evolution.

PMID- 15727231
TI  - Italian studies on early-onset multiple sclerosis: the present and the future.

PMID- 15727232
TI  - Late onset multiple sclerosis: clinical characteristics, prognostic factors and
      differential diagnosis.
AB  - Late onset multiple sclerosis (LOMS), defined as the first presentation of
      clinical symptoms in patients over 50, is not a rare phenomenon as previously
      thought, since the prevalence ranges between 4% and 9.6% in different studies.
      The course of the disease is often primary progressive and pyramidal or
      cerebellar involvement is observed in 60%-70% of the patients at presentation.
      LOMS is usually associated with a faster progression to disability compared to
      young adult multiple sclerosis (MS) patients. Moreover in patients over 50, MS
      variants and atypical forms which present a difficult diagnostic problem, may be
      frequently encountered. The differential diagnosis may be sometimes difficult and
      includes cerebro-spinal vascular syndromes, hypertension-related disorders,
      compressive myelopathies, primary or secondary vasculitis, metabolic diseases,
      degenerative and nutritional syndromes. Clinical characteristics, magnetic
      resonance imaging (MRI) pattern of abnormalities, evoked potential studies and
      cerebrospinal fluid (CSF) oligoclonal band analysis are of high diagnostic yield
      in LOMS patients, but expertise in interpreting their results is strongly
      required.

PMID- 15727233
TI  - Atypical multiple sclerosis: MRI findings and differential diagnosis.
AB  - In the past few years, magnetic resonance imaging (MRI) has become increasingly
      relevant in the diagnosis of multiple sclerosis (MS). Yet, the specificity of MR
      is limited. Atypical forms of MS and other diseases of the central nervous system
      may show similar patterns in MR. We briefly discuss the MR findings of the main
      MS-like diseases. Correct differential diagnosis can be carried out by combining
      the MR findings with clinical and laboratory findings.

PMID- 15727234
TI  - Marburg type and Balo's concentric sclerosis: rare and acute variants of multiple
      sclerosis.
AB  - Marburg type and Balo's concentric sclerosis are considered particular variants
      of multiple sclerosis, clinically characterized by a severe, rapidly evolving
      clinical course, and by unusual neuropathological changes, often large tumor-like
      demyelinating plaques in Marburg type and concentric layers of partial
      demyelination alternating with demyelinating bands in Balo's concentric
      sclerosis. These forms now can be diagnosed in vivo, with complete clinical and
      laboratory examination and MRI follow up. Although in some patients a favourable
      clinical course has been described, the poor prognosis of the majority of these
      cases justifies a treatment with intense immunosuppression.

PMID- 15727235
TI  - Devic's neuromyelitis optica: clinical features and prognostic factors.
AB  - Devic's neuromyelitis optica (NMO) onset is characterized by optic neuritis (ON)
      and transverse myelitis (TM), either simultaneously or in isolation. Thereafter,
      the course of the disease can be monophasic (no other attack) or relapsing
      (sequences of ON and TM, no other neurological system involved). The risk of
      having a relapsing course is related to gender, older age at onset, less severe
      motor impairment after the myelitic onset, interval length between first and
      second attack. The risk of an unfavourable evolution (severe disability or death)
      during a relapsing course is mainly related to high relapse rate during the first
      two years of the disease. In summary, relapsing NMO patients tend to have a poor
      prognosis, requiring more effective immunosuppressive treatments.

PMID- 15727236
TI  - Cerebrospinal fluid findings in Devic's neuromyelitis optica.
AB  - Relapsing Devic's neuromyelitis optica (DNO) may be clinically undistinguishable
      from multiple sclerosis (MS), thus the differential diagnosis relies mainly on
      neuroimaging and cerebrospinal fluid (CSF) findings. We studied CSF samples from
      44 patients with DNO submitted to at least one lumbar puncture. Pleocytosis, IgG
      synthesis and blood brain barrier damage were the most frequent abnormalities,
      pleocytosis being very suggestive of DNO in patients fulfilling clinical and MRI
      diagnostic criteria. Pleocytosis > or =50 cells/mm3 is more frequent in the
      active phases of the disease. Oligoclonal bands (OBs) should be re-considered
      within the diagnostic criteria of DNO for possible variations in time: at
      variance with MS they may also disappear. Thus, more than one CSF examination
      should be done in the presence of suspected DNO, preferably in different disease
      phases. Although uncommon, OBs do not exclude DNO if optic nerve and spinal cord
      are the only sites of white matter damage, provided that cerebral MRI is normal
      at onset and during follow up.

PMID- 15727237
TI  - MR imaging of Devic's neuromyelitis optica.
AB  - Devic's neuromyelitis optica (NMO) is a neurological condition characterized by a
      severe involvement of the optic nerves and spinal cord in a mono- or multi-phasic
      manner. Recent pathologic, cerebrospinal fluid and conventional magnetic
      resonance imaging (MRI) studies have shown abnormalities which might help in
      differentiating patients with NMO from those with multiple sclerosis. This review
      article summarizes the main results obtained using conventional MRI in NMO, which
      has contributed to the definition of internationally-accepted diagnostic
      criteria, and those obtained from the application of modem quantitative MR
      techniques which are significantly changing our views on NMO pathobiology.

PMID- 15727238
TI  - Multiple sclerosis: pseudotumoral forms.
AB  - The pseudotumoral forms of multiple sclerosis often represent a diagnostic
      problem. In this paper, the main clinical, radiological and pathological
      characteristics of these forms are described. A short overview on the main
      treatments used in these cases is also provided.

PMID- 15727239
TI  - Devic's neuromyelitis optica and mitochondrial DNA mutation: a case report.
AB  - Cases are described with Leber's optic atrophy and neurological symptoms and/or
      MRI lesions suggestive of multiple sclerosis. We describe a case of a young woman
      with Devic's neuromyelitis optica and 3460 homoplasmic mitochondrial DNA
      mutation.

PMID- 15727240
TI  - An unusual case with relapsing neuromyelitis optica associated with
      undifferentiated connective tissue disease.
AB  - A case is presented with attacks of optic neuritis followed by severe myelitis 15
      years later, in coincidence with a severe stressful life event. This female
      patient was also affected by undifferentiated connective tissue disease. This
      case presents some unusual and atypical findings such as: the association of a
      relapsing neuromyelitis optica with an undifferentiated connective tissue
      disease, a very long interval between optic neuritis and myelitis, and the
      important role of a stressful event in developing a relapse.

PMID- 15727241
TI  - Monofocal acute large demyelinating lesion mimicking brain glioma.
AB  - We report the case of a 34-year-old woman with clinical, neuroradiological and
      intraoperative histological findings, suggesting a low-grade astrocytic tumour.
      The demyelinating nature of the lesion was established through biopsy only after
      neurosurgery. The lesion size, in fact, greatly exceeded that of the perivenous
      demyelination seen in typical multiple sclerosis (MS) and tended to present as a
      space-occupying mass. This case underlines the importance of considering
      demyelinating isolated lesions in the differential diagnosis of a brain mass.
      Since misdiagnosis can result in unwarranted and aggressive therapy, it is
      critical for the neurologist to be aware of this serious diagnostic pitfall.

PMID- 15727243
TI  - Accuracy of cancer family histories: comparison of two breast cancer syndromes.
AB  - Cancer risk programs rely on accurately reported family history information. This
      study compares the accuracy with which cancer sites and ages at diagnosis are
      reported by Li-Fraumeni syndrome (LFS) and hereditary breast-ovarian cancer
      syndrome (HBOCS) families undergoing genetic testing. We analyzed the accuracy of
      191 cancer diagnoses among first-degree (FDRs) and second-degree (SDRs) relatives
      reported by 32 LFS and 52 HBOCS participants in genetic testing programs. Cancer
      diagnoses of relatives were more accurately reported in the HBOCS cohort (78%)
      than in the LFS cohort (52%). Almost all breast cancer diagnoses were accurately
      reported, whereas 74% of ovarian cancer diagnoses and only 55% of other LFS
      related cancers were accurately reported. Age at diagnosis was accurate within 5
      years for 60% of LFS relatives and 53% of HBOCS relatives. Factors correlating
      with accurate reporting of cancer history included: being member of BRCA1 family,
      higher education level, female historian, degree of closeness to affected
      relative, and having fewer than 5 affected FDRs and SDRs. Relying on verbal
      histories would not have altered eligibility for genetic testing among HBOCS
      historians, but fewer than half of LFS historians provided information that would
      have led to TP53 testing. Our data suggest that it may not be necessary to
      confirm breast cancer diagnoses routinely; however, documentation of other cancer
      types remains important for appropriate risk assessment and follow-up.

PMID- 15727244
TI  - Implications of the age range in a population-based BRCA1 testing program with
      eligibility based on family history of breast and ovarian cancer.
AB  - The current options available to BRCA1 mutation carriers can be classified as
      either cancer risk reduction or increased disease surveillance. Risk reduction
      might be preferable to young women. Increased surveillance might be more
      attractive to women when their cancer risk is highest. The aim of this report is
      to estimate the sensitivity, specificity and ability to detect carriers for a
      population-based BRCA1 testing program with eligibility based on family history
      of cancer, and examine the effect of age on the program's performance. A computer
      model was used to simulate the incidence of breast and ovarian cancer in a
      woman's family, based on her BRCA1 mutation carrier status. Age-specific
      estimates of the sensitivity and specificity for family history as an indicator
      of mutation status were applied to local population figures. Sensitivity of the
      program increased with the age of the proband and the size of her family.
      Sensitivity ranged from 0.33 for 20-year-olds with small families, to 0.98 for 60
      year-olds with large families. Specificity was greater than 0.95, regardless of a
      woman's age or family size. If 0.12% of people carry a BRCA1 mutation, a province
      wide testing program for people aged 20-69 with referrals based only on family
      history would have a sensitivity of 0.55. Only 2% of the genetic test results
      would be positive. The acceptability of a genetic testing program depends on its
      sensitivity and specificity, and on the options available to women who are found
      to carry a mutation. Compared with variation due to family size, the program
      sensitivity and specificity does not differ substantially amongst the various age
      groups.

PMID- 15727245
TI  - Variants of uncertain clinical significance as a result of BRCA1/2 testing:
      impact of an ambiguous breast cancer risk message.
AB  - The identification of an increasing number of variants of uncertain clinical
      significance (VUCS) in genetic testing for hereditary breast cancer poses serious
      problems for genetic counseling, because no data are available about the
      psychosocial impact of discussing such an unclear risk message. The current study
      is the first to present data on how test applicants actually understand and cope
      with such a result if communicated by a geneticist. We compared 10 women who
      received a VUCS result with 34 women who carried the deleterious mutation, 37
      women who did not carry the deleterious mutation or 'true negatives,' and 160
      women who received a so-called inconclusive result before and after test
      disclosure. Women, with whom a VUCS result was discussed, reported quite a high
      level of comprehension of the result. In addition, compared with the pretest
      measures, they did not report a higher level of perceived risk (p = 0.58) and
      even reported a decrease in breast cancer distress (p = 0.03). They were very
      comparable to women who received an inconclusive result on all post-disclosure
      measures. Our results suggest that discussing a VUCS result in genetic counseling
      does not give rise for concern.

PMID- 15727247
TI  - Identification of genomic deletions of the APC gene in familial adenomatous
      polyposis by two independent quantitative techniques.
AB  - Large deletions in the APC (adenomatous polyposis coli) gene, causing familial
      adenomatous polyposis (FAP), cannot easily be detected by conventional mutation
      detection techniques. Therefore, we have developed two independent quantitative
      methods for the detection of large deletions, encompassing one or more exons, of
      APC. Multiplex ligation-dependent probe amplification (MLPA) is performed in one
      reaction for the initial quantification of all APC exon copy numbers.
      Subsequently, quantitative real-time PCR (QRT-PCR) is used to verify the results
      obtained in the MLPA reaction. The identification of a deletion of the whole APC
      gene in a patient with classical FAP is described. The mutation was detected with
      the two quantitative methods and further verified on chromosomal level by the use
      of FISH (fluorescence in situ hybridization) on metaphase spreads. Furthermore, a
      large deletion covering exons 11-13 of the APC gene was detected in two
      apparently unrelated families. This deletion was further verified and
      characterized with long-range PCR. The MLPA test ensures a sensitive high
      throughput screening for large deletions of the APC gene and can easily be
      implemented in the diagnostic testing for FAP.

PMID- 15727246
TI  - Psychological impact of genetic testing for breast cancer susceptibility in women
      of Ashkenazi Jewish background: a prospective study.
AB  - The recognition that the prevalence of three founder mutations in the BRCA1 and
      BRCA2 genes is over 2% in Ashkenazi Jews has resulted in numerous epidemiological
      research studies of this ethno-religious group. To determine the effects of
      incorporating research into clinical practice, a psychological impact study of
      women participating in an epidemiological study was conducted. Sixty women of
      Ashkenazi Jewish background who underwent genetic testing for founder mutations
      were assessed using mailed, self-administered questionnaires with validated
      measures of psychological outcome. Forty-three women elected to learn their
      results and 17 women declined to do so. Women who elected to learn their results
      were also assessed 7-10 days, 4 months, and 12 months after results disclosure.
      Women who chose to learn their results had significantly higher baseline breast
      cancer anxiety, compared to those who elected not to learn their results (z = 
      2.27; p = 0.023). Unaffected women who elected to learn their results showed a
      significant decrease in breast cancer anxiety 4 months (z = -2.37, p = 0.018) and
      12 months (z = -3.06, p = 0.002) post-notification compared to baseline. Genetic
      testing for mutations common in Ashkenazi Jewish women with result disclosure
      does not lead to adverse psychological outcomes.

PMID- 15727248
TI  - Reliable and high-throughput mutation screening for beta-thalassemia by a single
      base extension/fluorescence polarization assay.
AB  - beta-thalassemia is one of the most common inherited diseases with incidence
      varying between 3% and 10% in the high-prevalence regions of South China. The
      molecular defects are mostly due to single-nucleotide substitutions, minor
      insertions, and deletions in the beta-globin gene. Large-scale population genetic
      screening combined with prenatal diagnosis is necessary for the effective
      prevention of this disease. We present a single base extension (SBE) method based
      on homogenous fluorescence polarization (FP) for simultaneous detection of the
      eight most common causative mutations [CDs 41-42 (-TCTT), IVS-2-654 (C-->T), -28
      (A-->G), CD17 (A-->T), CD 71/72 (+A), CD26 (G-->A), -29 (A-->G), and CD43 (G-
      >T)] in the beta-globin gene in a Chinese population. This assay has been
      validated by a blind experiment with 100 clinical samples previously
      characterized by reverse dot-blot and direct sequencing. The results demonstrate
      that this high-throughput method is simple, reliable, and cost effective. We
      expect this approach can be used in large-scale genetic screening for beta
      thalassemia.

PMID- 15727249
TI  - Frequency of HFE H63D, S65C, and C282Y mutations in patients with iron overload
      and controls from Toledo, Spain.
AB  - Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by a
      defective iron absorption. C282Y is the most frequent HFE gene mutation causing
      HH in Northern European populations and their descendants. However, two other
      mutations, H63D and S65C, have been described as pathogenic changes. In this
      study, we have tried to evaluate the frequency of these three mutations in our
      community. Eighty-three patients with clinical and/or biochemical features of
      hemochromatosis and 150 controls were screened for H63D, S65C, and C282Y
      mutations using a PCR-restriction fragment length polymorphism (RFLP)-based
      strategy. In contrast to previous studies, 7% of the patients were homozygous for
      C282Y mutation. The remaining patients were 20% H63D homozygous, 10% H63D/C282Y
      compound heterozygous, 1% H63D/S65C compound heterozygous, 22% H63D heterozygous,
      2% C282Y heterozygous, 2% S65C heterozygous, and 36% of patients lacked any of
      the three mutations studied, despite the fact that they showed
      clinical/biochemical features of hemochromatosis. We observed a high frequency of
      the H63D mutation in both the control group and patients, whereas the main
      genotypes implicated in HH in our series were H63D homozygous and H63D/C282Y
      compound heterozygous. We propose that the H63D mutation be analyzed in HH
      patients from our geographic area. Moreover, further studies are needed to
      elucidate the role of this mutation in the development of HH and the genetic,
      environmental or other factors that affect the genotype-phenotype correlation
      between H63D and hemochromatosis.

PMID- 15727250
TI  - Fanconi anemia: contribution of molecular analyses to the identification of bone
      marrow graft donors and the study of chimerism in grafted patients.
AB  - We report on the effectiveness of molecular studies regarding Fanconi anemia (FA)
      for a better selection of bone marrow graft donors and for post-transplant follow
      up. Ten unrelated FA patients and their families were analyzed by microsatellite
      markers. In 9 cases, the cytogenetic investigation of potential human leukocyte
      antigen (HLA)-identical related donors was normal, and the molecular analyses
      confirmed that they were also either normal or heterozygous carriers. For 1
      patient, cytogenetic analysis of an HLA-identical sibling donor yielded ambiguous
      results with a relatively high number of chromosomal breakages using cross
      linking agents. However, genotyping of this potential donor demonstrated his
      heterozygous state. Nine patients have received allogeneic bone marrow
      transplantation from HLA-matched related donors. Microsatellite analysis showed
      complete chimerism (CC) in all cases. The median follow up was 54 months (range 8
      144 months). One patient out of 9 with CC rejected her graft without prior
      detection of a transitional mixed chimerism. Among these patients, 1 died 25
      months after the transplantation of a chronic graft-versus-host-disease (GVHD).
      We conclude that, when the cytogenetic studies are not conclusive, molecular
      analyses are crucial to distinguish heterozygous carriers from asymptomatic FA
      Tunisian patients. Molecular analyses also allowed the evaluation of
      hematopoietic chimerism after allogeneic bone marrow transplantation and might be
      of value to identify patients with a high risk for graft rejection.

PMID- 15727251
TI  - Spectrum of cystic fibrosis mutations in Serbia and Montenegro and strategy for
      prenatal diagnosis.
AB  - We have screened 175 patients for molecular defects in the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene using nondenaturing
      polyacrylamide gel electrophoresis (PAGE), denaturing gradient gel
      electrophoresis (DGGE), and sequencing. Six different mutations (F508del, G542X,
      621+1G --> T, 2789+5G --> A, R1070Q, and S466X) accounted for 79.71% of CF
      alleles, with the F508del mutation showing a frequency of 72.28%. Another 12
      mutations (R334W, 2184insA, I507del, 1525-1G --> A, E585X, R75X, M1I, 457TAT -->
      G, 574delA, 2723delTT, A120T, and 2907delTT) covered an additional 3.36%. A novel
      mutation (2723delTT) was found in one CF patient (F508del/2723delTT). Thus, a
      total of 18 mutations cover 82.57% of CF alleles. During our study, 72% of
      families at risk for having a CF child were found to be fully informative for
      prenatal diagnosis. Prenatal diagnosis was performed on 56 families; 76 analyses
      resulting in 16 affected, 38 carriers, and 22 healthy fetuses. These results
      imply that the molecular basis of CF in Serbia and Montenegro is highly
      heterogeneous, as is observed in other eastern and southern European populations.
      Because we detected more then 80% of CFTR alleles, results could be used for
      planning future screening and appropriate genetic counseling programs in our
      country.

PMID- 15727252
TI  - Genetic polymorphism of MJD1 alleles and molecular analysis of SCA3 patients from
      Rio de Janeiro, Brazil.
AB  - Spinocerebellar ataxia type 3 is the most common form of autosomal dominant
      cerebellar ataxia. It is a severe progressive neurological disorder caused by an
      expansion of an exonic CAG repeat of the MJD1 gene. The repeated sequence is
      polymorphic among both normal individuals and patients. In general, expanded
      alleles are paternally inherited and the disorder exhibits anticipation. We
      performed a PCR-based study to determine polymorphisms of the number of CAG
      repeats of the MJD1 gene in an anonymous sample of normal Brazilian individuals.
      We also analyzed DNA samples from 9 patients with ataxia. We identified 29
      different allele sizes ranging from 12 to 40 CAG repeats, with heterozygosity of
      79%. The distribution of allele sizes showed two major peaks of 16 (7%) and 26
      (10.1%) CAG repeats. When grouping normal alleles by size, we observed that the
      distribution varies between males and females, and a significant deviation from
      the Hardy-Weinberg equilibrium was observed with an excess of normal large
      alleles among males. We also detected expanded alleles with 68-73 CAG repeats in
      3 out of 9 ataxic patients.

PMID- 15727253
TI  - X-linked Menkes disease: first documented report of germ-line mosaicism.
AB  - This work investigated a three-generation Menkes disease family, where germ-line
      mosaicism was suspected in the maternal grandmother of the index patient. She had
      given birth to 2 boys who died of suspected Menkes disease on the basis of
      clinical and photographic evidence. Biochemical analysis of the index patient
      confirmed the diagnosis of Menkes disease, and DNA analysis established a partial
      gene deletion (EX11_EX23del), involving exons 11-23 and the 3'-untranslated
      region (UTR) of ATP7A. A junction fragment was detectable by Southern blot
      analysis, which enabled carrier analysis. The mother was demonstrated to be a
      carrier, whereas analysis of lymphoblasts and skin fibroblasts from the maternal
      grandmother gave no indication of a partial gene deletion. No materials were
      available from the possibly affected maternal uncles. Further genetic analyses,
      including biochemical testing of the grandmother and haplotype analysis using
      four intragenic markers on DNA from selected members of the family, corroborated
      this finding. The combined results from DNA analyses showed that the grandmother
      had transmitted three different ATP7A haplotypes to her offspring: (1) the at
      risk allele (CA(B))-1 and the deletion; (2) the at-risk allele (CA(B))-1 without
      deletion; and (3) the second allele (CAB)-2 without deletion. In conclusion, our
      study demonstrated segregation of Menkes disease within the family investigated
      that can best be explained by extensive germ-line mosaicism in the maternal
      grandmother. The finding of germ-line mosaicism has obvious implications for
      genetic counseling of Menkes disease families.

PMID- 15727254
TI  - Efficient molecular diagnostic strategy for ABCC6 in pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is a hereditary disorder of connective tissue with
      skin, cardiovascular, and visual involvement. In familial cases, PXE usually
      segregates in an autosomal recessive fashion. The aim of this manuscript is to
      describe an efficient strategy for DNA diagnosis of PXE. The two most frequent
      mutations, R1141X and an ABCC6 del exons 23-29, as well as a core set of
      mutations, were identified by restriction enzyme digestion and size separation on
      agarose gels. Next, in the remaining patient group in which only one or no mutant
      allele was found, the complete coding sequence was analyzed using denaturing high
      performance liquid chromatography (dHPLC). All variations found were confirmed by
      direct DNA sequencing. Finally, Southern blot was used to investigate the
      potential presence of small or large deletions. Twenty different mutations,
      including two novel mutations in the ABCC6 gene, were identified in 80.3% of the
      76 patients, and 58.6% of the 152 ABCC6 alleles analyzed. With this strategy, 70
      (78.7%) out of 89 mutant alleles could be detected within a week. We conclude
      that this strategy leads to both reliable and time-saving screening for mutations
      in the ABCC6 gene in sporadic cases and in families with PXE.

PMID- 15727255
TI  - Five-locus HLA typing of hematopoietic stem cell donor volunteers using PCR
      sequence specific primers.
AB  - We have developed a strategy for five-locus human leukocyte antigen (HLA) typing
      of hematopoeitic stem cell (HSC) donors using the polymerase chain reaction with
      sequence-specific primers (PCR-SSP). The PCR-SSP method is robust, reproducible,
      and accurate. New PCR-SSP mixtures can be added as required and all reactions are
      carried out under the same conditions, which can easily be applied to the typing
      of other loci, e.g., ABO blood groups. Initially, 127 PCR-SSP reactions were used
      to detect simultaneously HLA-A, -B, -C, -DRB1/3/4/5, and DQB1 alleles,
      differentiated generally to the level of the first two digits of the allele name,
      essentially equivalent to the serological split specificity. Approximately 40% of
      subjects were tested against a further 29 HLA-A, -B SSP mixtures to exclude rare
      alleles and unambiguously assign a two-digit HLA allele family. This gave an
      overall typing resolution equivalent to or greater than the split specificity
      level and covered all HLA-A, -B, -C, -DRBland DQB1 alleles listed in the WHO's
      Nomenclature for Factors of the HLA System, 2000. The Welsh Bone Marrow Donor
      Registry has used this strategy to HLA type over 35,000 HSC donors over 9 years.
      Comprehensive and accurate five-locus HLA typing allows confident and rapid
      identification of potential matched HSC donors for patients requiring stem cell
      transplantation generally without the need for typing additional loci. This
      allows resources to be focused directly on allele level typing of DRB1 and other
      loci. This strategy decreases overall donor work-up time, which is a major
      benefit to patients.

PMID- 15727256
TI  - An RT-PCR-based strategy to estimate full-length CYP2D6 mRNA copy number.
AB  - The goal of this study is to develop an analytical tool to assess cytochrome P450
      2D6 (CYP2D6) levels in the form of full-length transcripts. CYP2D6 RNA in test
      samples was evaluated by co-amplification with an internal RNA control in a
      reverse-transcribed polymerase chain reaction (RT-PCR). The internal CYP2D6 RNA
      control was constructed by internally deleting 474 bp of CYP2D6 RNA, allowing
      simultaneous amplification of the test RNA together with the internal control RNA
      in a single RT-PCR reaction. With sequential dilution of test RNA, the CYP2D6
      mRNA transcript levels in test samples were estimated. The full-length RT-PCR
      strategy allowed semiquantitative assessments of CYP2D6 RNA transcripts with a
      sensitivity limit of 500 copies for CYP2D6 RNA transcripts, 2500 copies/microg
      total human liver RNA, and 10% intraday coefficient of variation (CV). In a
      method validation study, the CYP2D6 activity appeared to relate more closely to
      full-length CYP2D6 mRNA concentration than a short-sequence of CYP2D6 RNA
      estimated with a real-time quantitative RT-PCR assay. We have developed an
      efficient semiquantitative assay and demonstrated its suitability for estimating
      full-length CYP2D6 mRNA transcripts in cells and tissues.

PMID- 15727258
TI  - Evidence for duplication of the human defensin gene DEFB4 in chromosomal region
      8p22-23 and implications for the analysis of SNP allele distribution.
AB  - Defensins constitute a primary mechanism in the innate immune system of humans
      and all mammals. Defensins are short, processed peptide molecules that are
      classified by structure into three groups: alpha-defensins, beta-defensins and
      theta-defensins. In humans, four beta-defensins have been described so far,
      corresponding to the products of the genes DEFB1 (hBD1, NM_005218), DEFB4 (hBD2,
      NM_004942.2), DEFB103 (hBD3, NM_018661), and DEFB104 (hBD4, NM_080389),
      respectively. All these genes have been mapped to chromosome 8p22-23. Much
      interest has been shown in genetic variation in the population at defensin loci
      to understand individual differences in disease susceptibility and severity. In
      this study, we have used an electronic search and then fluorescence in situ
      hybridization (FISH) on elongated chromosomes to demonstrate that the region
      containing the DEFB4 gene is duplicated on human chromosome 8p, making difficult
      the discovery of new SNPs in this gene and compromising the assessment of their
      allelic distribution in various ethnic populations for disease association
      studies.

PMID- 15727257
TI  - Evidence for association of endothelial cell nitric oxide synthase gene
      polymorphism with earlier progression to end-stage renal disease in a cohort of
      Hellens from Greece and Cyprus.
AB  - Nitric oxide (NO) is thought to be an important factor in the deterioration of
      renal function. A variable-number tandem 27-bp repeat in intron 4 of the
      endothelial cell nitric oxide synthase (NOS3) gene has been found to be
      associated with the plasma levels of NO metabolites. Two alleles are of varied
      frequencies in different populations (a and b). The shorter allele a has been
      associated in Japanese populations with the progression of renal disease. Here we
      investigated this hypothesis by studying the putative role of this polymorphism
      in a Hellenic population of patients with end-stage renal disease (ESRD). We
      analyzed the genotypes of 361 ESRD patients and 295 healthy Hellens from Greece
      and Cyprus. The frequencies of NOS3-4bb, NOS3-4ab, and NOS3-4aa were 0.69, 0.27,
      and 0.03, respectively, in the control group and 0.71, 0.24, and 0.04 in the
      group of patients. The data in the two populations were analyzed by the chi
      square and Fisher's exact tests. The frequencies of these three genotypes of NOS3
      4 polymorphism in the Hellenic population of Greece and Cyprus are similar to
      those observed in other Caucasian populations. Moreover, our results from three
      patient groups, autosomal dominant polycystic kidney disease (ADPKD), diabetes
      mellitus (DM), and non-DM, showed that the frequencies of aa and ab genotypes in
      the patient populations were not significantly different from those observed in
      the control group. This work indicates that NOS3-4 polymorphism does not show any
      association with the development of ESRD in this studied European population.
      However, examination of the data regarding progression to ESRD within 5 years or
      after more than 5 years following clinical diagnosis of ADPKD provided evidence
      of statistical difference (p = 0.048, before Bonferroni correction), with faster
      progression in the group of ADPKD patients who carried allele a.

PMID- 15727259
TI  - Y chromosome microdeletions in infertile males from Andhra Pradesh, South India.
AB  - Studies on the frequency of Y chromosome microdeletions were carried out in 70
      idiopathic infertile males with normal karyotypes. Genomic DNA was isolated from
      blood and PCR analysis was carried out with AZFa, AZFb, and AZFc STS markers SY
      84, SY 87, SY 127, SY 254, and SY 158 to detect the deletions. In 9/70 (12.8%)
      subjects AZF deletions were observed. In 4/9 (44.4%) subjects were azoospermic,
      4/9 (44.4%) of cases were severe oligozoospermic, and 1/9 (11.1%) cases was
      oligozoospermic.

PMID- 15727260
TI  - Assessment of a decision aid to assist genetic testing research participants in
      the informed consent process.
AB  - Limited attention has been given to applying decision-making theories from
      psychology to the content and process of informed consent in genetic testing
      research. Data are presented from a study that developed and assessed a
      psychological theory-based decision aid as part of the informed consent process.
      This innovative approach assisted at-risk women in assessing the consequences of
      participating in a research project that offered them free hemophilia A genetic
      carrier testing. Results suggest: (1) the decision aid can be incorporated into
      the consent process with few problems; (2) women of varying educational
      backgrounds can complete the decision aid; (3) while women consider many
      consequences of genetic testing, their primary focus is on the implications for
      their family; and (4) this is in marked contrast to the typical benefit-harm
      statements prepared by researchers for genetic testing.

PMID- 15727261
TI  - Disclosure of genetic information obtained through research.
AB  - The rapid expansion of information and knowledge of genetics has implications for
      the question of whether, and under what circumstances, information discovered in
      the course of genetic research should be conveyed to research participants and/or
      their relatives. The aim of this paper is to propose an ethically defensible
      solution to a specific case example illustrating this problem. To do this we
      reviewed the literature to find answers to the following three questions: (1)
      What do current regulations, guidelines, and commentary say about the disclosure
      of genetic risk information obtained through research to research participants?
      (2) What do current regulations, guidelines, and commentary say about the
      disclosure of genetic risk information obtained through research to the relatives
      of research subjects? and (3) What do current regulations, guidelines, and
      commentary say about the disclosure of genetic risk information obtained through
      research about former research participants who are now deceased? Our conclusion
      is that current U.S. federal guidelines governing the use of human subjects in
      research, as well as much of the current literature, do not adequately address
      the familial dimension inherent in genetic research, are virtually silent on the
      issue of sharing information of relevance to family members, and do not protect
      the deceased. It is our belief that this omission needs to be corrected and that
      explicit guidance on this issue needs to be provided to institutional review
      boards and researchers alike.

PMID- 15727262
TI  - Managing familial risk in genetic testing.
AB  - Increasing numbers of people are seeking genetic testing and uncovering
      information that directly concerns their biological relatives as well as
      themselves. This familial quality of genetic information raises ethical
      quandaries for physicians, particularly related to their duty of confidentiality.
      In this article, the American Medical Association's Council on Ethical and
      Judicial Affairs examines the informed consent process in the specific context of
      genetic testing, giving particular consideration to the handling of information
      that has consequences for biological relatives. Furthermore, it addresses the
      question of whether physicians' obligation to warn biological relatives ever
      should override the obligation to protect patient confidentiality.

PMID- 15727263
TI  - 17O magnetic resonance imaging of the human brain.
AB  - Here we show the first example of in vivo oxygen-17 (17O) magnetic resonance
      imaging of the human in natural abundance. Two-dimensional fast multi-planar
      gradient recalled 90 deg echo (FMPGR/90) pulse sequence and three-dimensional
      projection reconstruction pulse sequence methods were used.

PMID- 15727264
TI  - Challenging Alexis Carrel: a study in alternate microvascular techniques.
AB  - INTRODUCTION: Alexis Carrel pioneered the full-thickness triangulated vascular
      repair technique, which led to a Nobel Prize in 1912. However, microvascular
      anastomotic techniques that do not violate the intima, such as the VCS microclip
      repair and partial-thickness suturing, limit trauma to the intima, thus
      minimizing the potential for thrombosis. Our study compares such techniques with
      the standard full thickness-anastomotic repair. METHODS: Thirty-two end-to-end
      anastomotic repairs were performed in rat femoral arteries 1 mm or less in
      diameter. Group I: thirteen full-thickness repairs were completed using 10-0
      nylon on a BV75 microm needle. Nineteen extraluminal repairs were performed using
      either a partial thickness technique with an 11-0 nylon BV50 microm needle (Group
      II, n = 12) or VCS nonpenetrating clip (Group III, n=7). Casted samples, injected
      with methylmethacrylate, were harvested at 1 and 3 weeks for histopathological
      evaluation. The presence of thrombosis, inflammation, endothelialization,
      angiogenesis and intimal hyperplasia were described for each repair. RESULTS:
      Statistical analysis revealed no difference between the intraluminal and
      extraluminal techniques. Patency rates were similar between both groups: 92%
      (12/13) for Group I and 94% (17/18) for the extraluminal Groups II and III
      combined. One-hundred per cent of partial thickness suture repairs were patent.
      Histology revealed localized inflammation to the adventitia and media, as well as
      endothelialization at 1 week for anastomoses in Groups II and III. The intima of
      Group I demonstrated proliferative characteristics in contrast to the
      extraluminal groups, where secretory myofibroblasts were prevalent. The
      anastomotic microcirculation did not originate from the repaired artery in any of
      the groups. CONCLUSION: Patency rates with end-to-end anastomotic repairs using a
      partial thickness technique are comparable to the standard full-thickness
      technique. Repairs that do not include the intima revealed focal inflammatory
      responses to the outer layers and more rapid endothelialization, while
      neighboring vessels perfuse the healing anastomosis.

PMID- 15727265
TI  - Perivascular delivery of neomycin inhibits the activation of NF-kappaB and MAPK
      pathways, and prevents neointimal hyperplasia and stenosis after arterial injury.
AB  - The nuclear transcription factor kappaB (NF-kappaB) is a cytoplasmic dimer that,
      as the family of mitogen-activated protein kinase (MAPK), can directly regulate
      the expression of early genes and genes involved in the stress response,
      following a variety of physiological or pathological stimuli. Both of them
      stimulate the transcription of many proteins, which are considered important
      during inflammation. A crucial role has been assigned to these factors in
      cellular proliferation and in neointimal hyperplasia secondary to the endothelial
      lesion of arterial vessels. On the other hand, it has been described that
      neomycin can have an inhibitory function on tumor cell proliferation, through the
      inhibition of different intracellular pathways of signaling, among them the NF
      kappaB and MAPK pathways. Rat common carotid artery was subjected to balloon
      angioplasty. Neomycin sulfate (18 mg) was applied using pluronic acid gel on the
      adventitial surface of the injured vessel. MAPK and NF-kappaB activation was
      quantified after 24 hours with immunohistochemical staining. Neointimal formation
      was quantified after 14 days with morphometry. Immunohistochemistry results
      demonstrating MAPK and NF-kappaB activation reveal that both transcription
      factors are activated in the media of the control vessel wall. In contrast, the
      immunoreactivity for MAPK and NF-kappaB in the sections obtained from arteries
      treated with neomycin over 24 hours was insufficient or nonexistent. Treatment
      with neomycin on adventitia over 14 days in arteries on which angioplasty was
      performed shows a neointimal index (intimal area/medial area) decrease of 71% in
      comparison with arteries that were not treated. The adventitial neomycin
      treatment over 14 days produces a very significant increase (287.5%; p<0.0001) in
      the arterial luminal circumference in comparison with arteries treated with
      vehicle. These results support the theory that neomycin plays an important role
      against neointimal hyperplasia through the inhibition of MAPK and NF-kappaB
      activation.

PMID- 15727266
TI  - Ischemic neuronal cell death and organellae damage.
AB  - The brain is an organ that consumes much energy. This is partially due to the
      character of neurons; they possess excitable plasma membrane and a large amount
      of ATP is indispensable for maintaining ion gradient. Once neurons experience
      energy failure, calcium accumulates in the intracellular space as a result of
      disturbed ion homeostasis. This, in turn, activates many cellular processes,
      which culminate in cell death. In this cellular catastrophic cascade, many
      organelles play important roles. In addition to the plasma membrane, cytosol is
      the 'organelle' that first becomes exposed to the increased level of calcium.
      Many proteases, kinases and lipases are localized here, and are activated
      directly or indirectly by the ischemic insult. Some enzymes are pro-apoptotic
      ones, while others are anti-apoptotic. It was reported that neurons that would
      die later showed activated pro-apoptotic enzymes, but ones that would survive
      possessed activated anti-apoptotic molecules. Mitochondria is the organelle that
      plays the central role for intrinsic pathways of apoptosis. The release of
      cytochrome c from this organelle is the key step in apoptotic cascade in the
      ischemic neurons. However, the exact molecular mechanism of cytochrome c release
      remains uncertain. In addition, expression of genes essential for mitochondrial
      function changes in neurons after ischemia, which further indicates the crucial
      role of this organelle in cell death. Endoplasmic reticulum (ER) not only
      mediates proteins processing, but also regulates intracellular calcium
      homeostasis and cell death signal activation. Recent reports indicate that
      dysfunction of this organelle occurs at an early stage after ischemia and might
      be the initial step of apoptotic cascades in neurons. Golgi apparatus and
      lysosomes are organelles that are involved in apoptotic cell death in some
      situations. There have been no reports that demonstrated active role of these
      organelles in ischemic neuronal cell death. Further investigation would be
      desired about this issue. Nucleus is the organelle that contains genomic DNA.
      Many studies demonstrated DNA breakage in the neurons that would die later, but
      whether this is the cause or merely the result of the insult remains uncertain.
      If the more precise role of each organelle in neuronal cell death are disclosed,
      we should be able to think about new means of therapy for ischemic stroke.

PMID- 15727267
TI  - Apoptosis in cerebral ischemia: executional and regulatory signaling mechanisms.
AB  - Programmed cell death, often in the form of apoptosis, is an important
      contributing mechanism in the pathogenesis of ischemic brain injury. Depending on
      the severity of the insult and the stage of the injury, the executional pathways
      that are directly responsible for cell death and the signaling mechanisms that
      participate in the regulation of these death pathways may vary. It is likely that
      molecular or pharmacological targeting of the upstream signaling mechanisms that
      control the death executional pathways may offer opportunities for more complete
      and long-term neuroprotection. This review summarizes the recent advancements in
      the understanding of the executional and regulatory signaling mechanisms in
      ischemic brain injury.

PMID- 15727268
TI  - The cerebral vasculature as a therapeutic target for neurological disorders and
      the role of shear stress in vascular homeostatis and pathophysiology.
AB  - It is widely accepted that vascular mechanisms are involved in the genesis of
      many neurological disorders. In particular, blood-brain barrier (BBB) dysfunction
      has been related to the severity of Alzheimer's disease, encephalopathy due to
      meningitis, multiple sclerosis, HIV-associated encephalopathy, epilepsy, gliomas
      and metastatic brain tumors. The BBB may constitute an important therapeutic
      target to protect neurons after CNS diseases. Both in vivo and in vitro, the
      functional phenotype of vascular endothelium is dynamically responsive to
      circulating cytokines, growth factors and puslatile blood flow (shear stress).
      Shear stress can play a critical role in vascular homeostasis and
      pathophysiology; it is a major regulator of remodeling in developed blood vessels
      and in blood vessels affected by atherosclerotic lesions. The physiological fluid
      mechanic stimulus, shear stress, could be considered to be an important
      'differentiative' stimulus capable of modulating endothelial phenotype in vivo.
      Endothelial cells undergo cell cycle arrest after exposure to physiological
      levels of shear stress. As for mature endothelial cells, in which flow mediated
      shear stress may play a role in the induction, progression and/or prevention of
      atherosclerosis by changing their function, stress may play a role in endothelial
      cell differentiation from hemopoietic stem cells and/or from embryonic stem
      cells. Stem cells may be used to repair vascular damage, including loss of EC,
      due to a variety of diseases (e.g. myocardial neovascularization by adult bone
      marrow derived angioblasts). In the brain, it was proposed that neuron-producing
      stem cells may be used to treat Alzheimer's disease, paralysis, etc.
      Surprisingly, very few investigators are exploring the use of endothelial
      precursors to revert or prevent cerebrovascular disease. This review summarizes
      the most recent data related to cerebral vasculature as a therapeutic target for
      neurological disorders and the role of shear stress in blood-brain barrier
      homeostasis and pathophysiology.

PMID- 15727269
TI  - Extracellular proteolytic pathophysiology in the neurovascular unit after stroke.
AB  - The NINDS Stroke Progress Review Group recommended a shift in emphasis from a
      purely neurocentric view of cell death towards a more integrative approach
      whereby responses in all brain cells and matrix are considered. The neurovascular
      unit (fundamentally comprising endothelium, astrocyte, and neuron) provides a
      conceptual framework where cell-cell and cell-matrix signaling underlies the
      overall tissue response to stroke and its treatments. Here, we briefly review
      recent data on extracellular proteolytic dysfunction in the neurovascular unit
      after a stroke. The breakdown of neurovascular matrix initiates blood-brain
      barrier disruption with edema and/or hemorrhage. Endothelial dysfunction
      amplifies inflammatory responses. Perturbation of cell-matrix homeostasis
      triggers multiple cell death pathways. Interactions between the major classes of
      extracellular proteases from the plasminogen and matrix metalloprotease families
      may underlie processes responsible for some of the hemorrhagic complications of
      thrombolytic stroke therapy. Targeting the proteolytic imbalance within the
      neurovascular unit may provide new approaches for improving the safety and
      efficacy of thrombolytic reperfusion therapy for stroke.

PMID- 15727270
TI  - Vascular aspects of neuroprotection.
AB  - It is being increasingly suggested that the microcirculation, which is known to
      be in a large part responsible for maintaining an adequate and constant
      microenvironment for function of the central nervous system, functions as part of
      a neurovascular unit. The neurovascular unit includes neurons, astrocytes and
      elements of capillaries. The cerebral circulation exhibits unique functional
      characteristics and critical elements for the pathogenesis of cerebrovascular
      disease. For example, the blood-brain barrier formed by epithelial-like high
      resistance tight junctions within the endothelium is a key feature of
      microvessels of the central nervous system. Alterations in the microcirculation
      after ischemia/reperfusion include disruption of the blood-brain barrier, edema
      and swelling of perivascular astrocyte foot processes, decrease in arteriole
      endothelium-dependent relaxation and reduced inwardly-rectifying potassium
      channel function, altered expression of proteases and matrix metalloproteinases,
      increased inflammatory mediators and inflammation. Experiments studying the
      microcirculation in ischemia are few compared with those examining
      neuroprotection, although the two overlap because protection of the
      microcirculation might achieve some degree of neuroprotection and both processes
      may be mediated by at least some mechanisms in common.

PMID- 15727271
TI  - The neurovascular unit and its growth factors: coordinated response in the
      vascular and nervous systems.
AB  - The nervous and vascular systems contain many common organizational features and
      develop similarly in terms of anatomical patterning. During embryogenesis and in
      regions of the brain undergoing postnatal neurogenesis, neural stem cells and
      endothelial cells are found in close proximity, or within a so-called vascular
      niche. The similarities in patterning and proximity may reflect coordinated
      development based on responsiveness to similar growth factors such as vascular
      endothelial growth factor, semaphorin, and ephrins/Ephs: molecules involved in
      the development and maintenance of both the nervous and vascular systems. Despite
      the blatant similarities between the vascular and nervous systems, little is
      still known about the co-dependence and/or interactions between the two systems
      during development and following alterations in metabolic demand as seen during
      aging, exercise, and disease processes. The interactions between the two systems
      involving common growth factors suggest these two systems have evolved in an
      interconnected way.

PMID- 15727272
TI  - Post-ischemic inflammation: molecular mechanisms and therapeutic implications.
AB  - Ischemic stroke is characterized by the disruption of cerebral blood flow (CBF).
      This reduction of CBF results in energy failure and secondary biochemical
      disturbances, eliciting a robust in situ inflammatory response. Post-ischemic
      inflammation is a dynamic process involving a complicated set of interactions
      among various inflammatory cells and molecules. The resident inflammatory brain
      cells, microglia, are especially activated in response to ischemic insults, many
      of which are regulated by nuclear transcription factor, kappa B (NF-kappaB). As a
      result, several inflammatory genes are expressed, leading to local generation of
      various cytokines, which in turn promulgate inflammatory signals. Meanwhile,
      endothelial cells lining the local cerebral blood vessels are stimulated to
      produce adhesion molecules, causing the migration of peripheral circulating
      leukocytes into the compromised brain tissue, an event that amplifies
      inflammatory signaling cascades. Post-ischemic inflammation appears to serve
      multiple purposes, depending on its timing and magnitude, as well as the
      topographic distribution of various inflammatory molecules. Data from
      experimental manipulations of some inflammatory molecules are yielding insight
      into therapeutic strategies for ischemic stroke. This review focuses on some
      recent advances regarding the regulation of inflammatory signaling pathways, the
      detrimental effects of post-ischemic inflammation and the potential molecular
      targets for ischemic stroke therapy.

PMID- 15727274
TI  - Nurse anesthetists and the Americans With Disabilities Act.

PMID- 15727273
TI  - High plasma concentration of brain natriuretic peptide in patients with ruptured
      anterior communicating artery aneurysm.
AB  - The purpose of this study is to investigate the mechanism of increased atrial
      natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with
      subarachnoid hemorrhage due to ruptured aneurysms. ANP and BNP plasma
      concentrations were measured by immunoradiometoric assay in 53 patients at the
      day of onset of ruptured aneurysm, the correlation between values of increased
      ANP or BNP, and sex, age, location of ruptured aneurysm, degree of SAH, and
      severity of WFNS were statistically studied. The concentration of BNP in ruptured
      anterior communicating artery aneurysm (A-com) shows a significant elevation
      compared with other site aneurysms (p = 0.0007). The patients classified as WFNS
      Grade V, show a significantly higher concentration of BNP, compared with the
      patients classified as Grade I-IV (p =0.01). It is concluded that the
      hypersecretion of BNP, but not ANP, is caused by direct mechanical damage at the
      anterior hypothalamus by ruptured A-com aneurysm and a higher increase of BNP is
      also observed in cases suffering from severe neurological deficit.

PMID- 15727275
TI  - Just following orders.

PMID- 15727276
TI  - Diagnosis and treatment of negative pressure pulmonary edema in a pediatric
      patient.

PMID- 15727277
TI  - The use of the laryngeal mask airway with mechanical positive pressure
      ventilation.

PMID- 15727278
TI  - The self-evaluation examination: past, present and future.
AB  - The Self-Evaluation Examination (SEE) was first administered in 1991. The purpose
      of the SEE has not changed since its inception. The purposes of the SEE are to
      (1) provide information to the students about their progress in the nurse
      anesthesia program, (2) to prepare students to take the National Certification
      Examination, and (3) to provide information to program directors on how well
      their students are performing. The SEE is administered as a computer adaptive
      examination. The blueprint for the SEE is derived from the Council on
      Accreditation of Nurse Anesthesia Educational Programs (COA) curriculum
      requirements. In 2006, the blueprint of the SEE will be changed to reflect the
      recent changes in the curriculum requirements from the COA. At the same time, the
      scoring of the SEE will also change. Scaled scores will no longer be reported for
      the SEE. The content of this editorial will be presented during the Assembly of
      School Faculty in February 2005. Program faculty will have the opportunity to
      seek clarification on the forthcoming changes in the SEE.

PMID- 15727279
TI  - Impact of the clinical doctorate from an allied health perspective.

PMID- 15727280
TI  - The use of a computer website prior to scheduled surgery (a pilot study): impact
      on patient information, acquisition, anxiety level, and overall satisfaction with
      anesthesia care.
AB  - Scheduled surgery can often be a stressful time for patients. While anesthesia
      providers give a full explanation of care to the patient, research suggests that
      anxiety and time constraints imposed by the system may hinder the amount and
      quality of information provided. Use of technology to augment dissemination of
      information may have an impact. The purpose of this study was to determine the
      impact of a website on: (1) preoperative patient education, (2) patient anxiety,
      and (3) patient satisfaction with anesthesia care. The week prior to surgery, 64
      ASA class I and II subjects at a 350-bed urban university affiliated hospital
      completed a demographic questionnaire, State Trait Anxiety Inventory (STAI) and
      modified Standard Anesthesia Learning Test (mSALT), and the experimental group
      was given website information. On the day of surgery, all subjects completed the
      STAI and mSALT. Before discharge, subjects rated satisfaction. The experimental
      group had a significant increase in posttest mSALT scores (P = .004). Neither the
      experimental nor the control group had a significant change in posttest state
      anxiety (P = .279 and .762) or trait anxiety (P = .823 and.570). The experimental
      group differed significantly from the control group in satisfaction with teaching
      (P = .019).

PMID- 15727281
TI  - Sevoflurane administration in status asthmaticus: a case report.
AB  - This case report describes the use of sevoflurane in a 26-year-old woman who
      presented to a rural critical access hospital emergency department in status
      asthmaticus and subsequently failed conventional therapy. Although the use of
      potent inhalation agents in the treatment of refractory status asthmaticus has
      been documented, there is little written about the use of sevoflurane in this
      situation. Sevoflurane was administered for approximately 2(1/2) hours,
      stabilizing the patient's condition enough to allow fixed-wing air transport to a
      tertiary facility.

PMID- 15727282
TI  - Novel pharmacological approaches for the antagonism of neuromuscular blockade.
AB  - Gamma cyclodextrin and purified plasma cholinesterase are 2 novel pharmacological
      agents being investigated as to their suitability for antagonism of neuromuscular
      blockade. Both of these agents are devoid of cholinergic stimulation and the
      accompanying side effects because their action is independent of
      acetylcholinesterase inhibition. Gamma cyclodextrin antagonizes the steroidal
      neuromuscular blocker rocuronium via the chemical encapsulation of the molecule
      forming a "host-guest" complex through van der Waals and hydrophobic interactions
      in the plasma. Encapsulation decreases plasma drug concentrations, shifting the
      neuromuscular blocking drug molecules from the neuromuscular junction back to the
      plasma compartment resulting in a rapid recovery of the neuromuscular function.
      Org 25969, a modified gamma cyclodextrin, will antagonize profound neuromuscular
      block induced by rocuronium in approximately 2 minutes. A commercial preparation
      of purified human plasma cholinesterase has been shown to be effective in
      reversing succinylcholine or mivacurium-induced block. Administration of
      exogenous plasma cholinesterase also has been shown to be effective in
      antagonizing mivacurium-induced neuromuscular block, cocaine toxicity, and
      organophosphate poisoning.

PMID- 15727283
TI  - Alkaptonuric ochronosis: a case report.
AB  - Alkaptonuric ochronosis is a rare autosomal recessive metabolic disorder
      resulting in a deficiency of homogentisic acid oxidase (alkaptonuria).
      Ultimately, this enzyme deficiency enables homogentisic acid to accumulate,
      become polymerized, and be systemically deposited within various tissues of the
      body (ochronosis). As the disease progresses, tissue deposition of polymerized
      homogentisic acid eventually will lead to the progressive degeneration of all
      affected body systems. There is no definitive cure for alkaptonuric ochronosis,
      and treatment is aimed at controlling and ameliorating symptoms. Multiple
      systemic complications occur as a result of alkaptonuric ochronosis. In the
      skeletal system, cervical, thoracic and lumbosacral degenerative disk disease
      develops, as do widespread arthritic changes in peripheral and weight-bearing
      joints. In the respiratory system, dyspnea can develop owing to limited chest
      excursion as a result of stiffening of cartilage in the chest wall. In the
      cardiovascular system, coronary and valvular calcification frequently occurs. In
      the genitourinary system, calculi formation and urine discoloration are chief
      manifestations. This case report describes a 63-year-old man with alkaptonuric
      ochronosis who sustained a stress fracture of the left femoral neck,
      necessitating surgical repair, which was done without complications. An overview
      of alkaptonuric ochronosis is presented, and anesthetic implications are
      discussed.

PMID- 15727284
TI  - Effects of hypothermia and shivering on standard PACU monitoring of patients.
AB  - Inadvertent postoperative hypothermia is common among patients in the
      postanesthesia care unit (PACU). Shivering traditionally is attributed to
      hypothermia, but it is not always thermoregulatory. The exact impact of
      hypothermia and shivering on standard PACU monitoring parameters of patients has
      not been sufficiently studied. The present study included 170 orthopedic surgical
      patients. On PACU arrival, we recorded the incidence of hypothermia and
      shivering, as well as heart rate, mean arterial blood pressure, and oxygen
      saturation of all subjects. Analysis of covariance was used to investigate the
      effects of hypothermia and shivering on these monitoring parameters. Among
      orthopedic patients, 73.5% of them had hypothermia and 24.7% experienced
      shivering, which was observed primarily in hypothermic patients. Mean arterial
      blood pressure was significantly higher in hypothermic patients, and heart rate
      was significantly higher in shivering patients, whereas oxygen saturation was not
      affected by hypothermia or shivering. Our data confirm that standard PACU
      monitoring parameters are affected partially by hypothermia and shivering. A low
      incidence of shivering in normothermic patients and a high incidence of shivering
      in younger patients are discussed. Limitations of this study are reported.

PMID- 15727285
TI  - Anesthetic management of a patient with a mediastinal foregut duplication cyst: a
      case report.
AB  - Foregut duplication cysts are rare. There is no mention of this type of
      mediastinal mass in searches of the anesthesia literature. A 42-year-old woman
      undergoing preoperative evaluation for elective bilateral breast augmentation was
      found by chest radiograph to have a mediastinal mass. She was referred for
      additional evaluation. After thorough radiographic and physical examination, the
      patient underwent successful resection of a foregut duplication cyst that
      involved esophageal, right lung, pericardial, and subcarinal tissues. The
      location of the foregut duplication cyst, its mass effect, and the anatomical
      structures involved with the cyst may present numerous challenges for anesthesia
      providers. Airway management, arterial cannulation, and central venous access may
      be difficult. In addition, patients with foregut duplication cysts are at risk
      for pneumothorax, pneumomediastinum, profound hemorrhage, esophageal injury or
      rupture, vascular lesions, neurologic injury, gastric aspiration, and
      cardiovascular collapse due to anatomical disturbances caused by the mass.
      Comprehensive evaluation and development of an anesthetic plan based on this
      evaluation will improve patient outcome and help prevent potentially catastrophic
      complications.

PMID- 15727286
TI  - AANA journal course: Update for nurse anesthetists--part 6--The long-term use of
      opiates for pain control: Laputa revisited?
AB  - Research seeking to resolve issues regarding the use of opiate analgesia in
      treating non-cancer-related chronic pain is confusing. In caring for a patient
      experiencing pain, the relief of pain is the primary objective. Yet a number of
      significant concerns arise when evaluating and using opiates on a long-term
      basis. Specifc and measurable outcomes of functionality are available to guide
      use; attention to these may help to significantly improve outcome of long-term
      opiate therapy. This course provides an evidence-based approach to selecting and
      using opiates in the management of chronic, non-cancer-related pain, critiquing
      the appropriateness of the associated intervention(s).

PMID- 15727287
TI  - Medetomidine with ketamine and bupivacaine for epidural analgesia in buffaloes.
AB  - The efficacy of ketamine and bupivacaine in enhancing the epidural analgesia
      induced by medetomidine was evaluated in 10 buffalo calves utilized repeatedly
      after a gap of 10 days so that each drug combination was tested in 4 randomly
      selected animals. In group A, medetomidine (15 microg/kg), in group B ketamine
      (2.0 mg/kg), in group C bupivacaine (0.125 mg/kg), in group D medetomidine and
      ketamine (15 microg/kg and 2.0 mg/kg), and in group E medetomidine and
      bupivacaine (15 microg/kg and 0.125 mg/kg) was administered epidurally. Onset of
      analgesia was significantly earlier in animals of groups B and D compared to the
      animals of groups A, C and E. Medetomidine alone or in combination with
      ketamine/bupivacaine produced complete analgesia of the tail, perineum, inguinal
      region and upper parts of hind limbs. Ketamine produced a very short duration of
      complete analgesia at the tail and perineum. Bupivacaine alone produced only mild
      to moderate analgesia. Both ketamine and bupivacaine prolonged the duration of
      analgesia. Motor incoordination was mild to moderate in animals of all the
      groups, but animals remained standing throughout the period of observation.
      Animals of groups A, D and E showed mild to moderate sedation during the
      observation period. Ruminal movements decreased nonsignificantly in animals of
      groups A and E. Mild salivation was observed in animals of all the groups except
      group C. Significant decrease in heart rate (HR) was recorded after epidural
      administration of medetomidine or bupivacaine; however, ketamine caused short
      duration of tachycardia. The administration of ketamine with medetomidine caused
      lesser decrease in HR compared to medetomidine alone or in combination with
      bupivacaine. Significant fall in respiratory rate (RR) was recorded after
      epidural administration of medetomidine or bupivacaine alone, but an increase in
      RR was recorded after ketamine administration. The fall in RR was less pronounced
      in animals in which medetomidine was used with ketamine compared to the animals
      in which medetomidine was used alone or in combination with bupivacaine. Mean
      arterial pressure (MAP) decreased and central venous pressure (CVP) increased
      significantly after epidural administration of medetomidine in combination with
      ketamine or bupivacaine. The ECG changes included tall T wave, QS pattern, RS
      pattern and ST elevation and heart blocks at different intervals, which were more
      frequent and pronounced in animals given bupivacaine with medetomidine. It can be
      concluded that epidural administration of medetomidine can produce complete
      analgesia of the tail, perineum, inguinal region and upper hind limbs in
      buffaloes. However, significant depression of cardiovascular parameters was
      recorded. Administration of ketamine along with medetomidine resulted in
      significantly early onset and slightly longer duration of analgesia with lesser
      cardiopulmonary side-effects compared to medetomidine alone or medetomidine with
      bupivacaine. Addition of ketamine to medetomidine thus seems to be useful for
      producing epidural analgesia; however, addition of bupivacaine failed to provide
      any advantage over medetomidine alone.

PMID- 15727288
TI  - Changes in activities of enzymes related to energy metabolism in peripheral
      leukocytes of fattening steers.
AB  - Glucose, triglyceride, cholesterol and immunoreactive insulin (IRI)
      concentrations, some enzyme activities in plasma, and activities of enzymes
      related to energy metabolism in peripheral leukocytes were measured in fattening
      Japanese Black Wagyu x Holstein steers fed on different diets at 8, 12, 16, 20
      and 24 months of age. The plasma IRI concentrations at 20 and 24 months of age
      were significantly higher than those at 8 months of age. Activities of hexokinase
      (HK), glucose-6-phosphate dehydrogenase (G6PD), aspartate aminotransferase (AST),
      and malate dehydrogenase (MDH) in cytosolic fractions, and glutamate
      dehydrogenase (GLDH), MDH and AST in mitochondrial fractions in peripheral
      leukocytes of steers at 24 months of age were significantly higher than those at
      8 months. Increasing plasma insulin concentration was considered to induce
      acceleration of glucose utilization in leukocytes of fattening steers. The
      cytosolic ratio of MDH/lactate dehydrogenase (LDH) activity in leukocytes
      increased significantly in the fattening process and was considered to be a
      useful indicator for evaluating changes in energy metabolism in steers.

PMID- 15727289
TI  - Enhanced erythrocytic lipid peroxides and reduced plasma ascorbic acid, and
      alteration in blood trace elements level in dairy cows with mastitis.
AB  - Oxidative stress has been associated in several inflammatory conditions and
      incriminated in the pathogenesis of many diseases. However, little information is
      available on the status of plasma antioxidant levels, essential components of
      important antioxidant enzymes such as copper, zinc and selenium in blood, and the
      end product of oxidative damage to the erythrocytic polyunsaturated fatty acids
      in inflammatory udder conditions. Blood samples were collected from three groups
      of dairy cows, with 21 in each group: animals with healthy udder, clinical
      mastitis, and subclinical mastitis. These animals were randomly selected from a
      herd on the basis of the California mastitis test, somatic cell count and total
      bacterial count. The mean plasma ascorbic acid concentration was significantly
      lower in cows with subclinical (p = 0.004) and clinical mastitis (p = 0.000) and
      the erythrocytic lipid peroxide levels were significantly (p = 0.000) higher in
      clinical mastitis as compared to controls. There was a significant decrease in
      mean blood zinc concentration in subclinical (p = 0.005) and clinical mastitis (p
      = 0.000), but an increase in mean blood copper level in the clinical mastitis
      group. It was concluded that the blood antioxidant status declines in
      inflammatory udder conditions, suggesting that incorporation of antioxidants may
      help in better management of mastitis in dairy cows.

PMID- 15727290
TI  - DNA fragment encoding human IL-1beta 163-171 peptide enhances the immune
      responses elicited in mice by DNA vaccine against foot-and-mouth disease.
AB  - DNA vaccine has been tested for protection against foot-and-mouth disease.
      However, the relatively low efficacy of DNA vaccine in inducing immune responses
      in large animals has restricted its practical use. Interleukin-1 plays an
      essential role in amplifying both the cellular and humoral immune responses to
      foreign antigens, and may therefore represent a good candidate as an adjuvant of
      DNA vaccines. Since the inflammatory activity of IL-I may restrict its
      application in DNA vaccine treatment, we explored the possibilities of augmenting
      immune responses without unwanted inflammatory effects using the IL-1beta
      fragment (amino acids (aa) 163-171), which is essential for IL-1 receptor-1
      binding. The DNA fragment encoding the human IL-1beta fragment (aa 163-171) was
      fused to foot-and-mouth disease virus (FMDV) DNA vaccine, and injected into mice
      to analyse its immune response. Compared with control mice receiving FMDV DNA
      vaccine alone, significant increases in the FMDV-specific antibody response and
      also in T cell proliferation were observed in mice receiving IL-1beta (163-171)
      FMDV. These results suggested that DNA fragment encoding IL-1beta 163-171 peptide
      might represent a good candidate for an adjuvant of FMDV DNA vaccine.

PMID- 15727292
TI  - Disseminated intravascular coagulation in cattle with abomasal displacement.
AB  - The purpose of the study was to evaluate haemostatic function in cattle with
      abomasal displacement (AD) and to reflect the occurrence of disseminated
      intravascular coagulation (DIC). Ten adult cattle with left displacement of
      abomasum (LDA) (group I), 10 adult cattle with right displacement of abomasum
      with volvulus (RDA) (group II) and 10 clinically healthy adult cattle (control
      group) were used as material. Numbers of platelets (PLT) and coagulation tests
      (activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin
      time (TT), serum fibrin/fibrinogen degradation products (FDPs), fibrinogen) were
      measured before the surgical treatment of cattle with LDA and RDA. APTT was
      prolonged only in group II compared with the control and group I (p<0.05).
      However, when the individual values of coagulation profiles of each cow were
      evaluated, two cattle in group I and three cattle in group II had at least three
      abnormal coagulation profiles, which reflect the occurrence of DIC. These cattle
      died after surgical treatment. The two cattle with LDA had abnormal APTT, FDPs
      and PLT values; three cattle with RDA had abnormal APTT, PT, TT, FDPs and PLT
      values. APTT (5 cases), FDPs (5 cases) and thrombocytopenia (5 cases) were the
      three most common abnormal tests on coagulation profile in the cattle with LDA
      and RDA. The results of the study indicate that cattle with AD had a spectrum of
      haemostatic dysfunction and that DIC was a significant risk factor for mortality.

PMID- 15727291
TI  - Comparison of immunosuppression in dry and lactating Awassi ewes due to water
      deprivation stress.
AB  - In seminomadic farming practice, dry and lactating ewes are exposed to different
      degrees of water deprivation, leading to stress followed by various disease
      outbreaks. This study compares quantitatively the immunosuppression to Salmonella
      Enteritidis (SE) fimbriae (14 and 21 kDa) and other major polypeptides (28.9,
      37.7, 42.9, 68.0, 92.6 and 96.8 kDa) in water-deprived dry and lactating ewes.
      Sixteen dry and lactating multiparous Awassi ewes were divided into four
      treatment groups (A, A', B and B'). Ewes in groups A and B were lactating,
      whereas ewes in groups A' and B' were dry. All ewes were administered a killed SE
      vaccine, subcutaneously in the neck, at the initiation of the experiment. The
      water availability for ewes in groups B (lactating) and B' (dry) was ad libitum,
      while that for ewes in groups A (lactating) and A' (dry) was once every 4 days. A
      serum sample was collected from the jugular vein of each ewe at zero time
      (initiation of the experiment, when SE bacterin was delivered) and at 2, 9, 12,
      15 and 18 days post SE vaccination. The percentage reduction in the level of
      humoral antibody response to polypeptides of > or = 21 kDa was more apparent in
      water-deprived lactating ewes of group A between 9 and 18 days post initiation of
      thirst. In this period, immunosuppression to polypeptides > or = 21 kDa was
      present in 14 out of 16 observations in group A (water-deprived lactating), with
      significant immunosuppression in 9 observations in relation to the respective
      control (p<0.05), while it was present in only 4 out of 16 observations in group
      A' (water-deprived dry), with significant immunosuppression in 2 observations (p
      <0.05). In conclusion, immunosuppression to polypeptides of > or =21 kDa is more
      significant in lactating water-deprived ewes in the period 9-18 days post
      initiation of thirst, a result that will influence our future sheep welfare
      awareness programmes targeting an elimination of the practice of water
      deprivation in seminomadic sheep farming.

PMID- 15727293
TI  - Disposition kinetics, bioavailability and renal clearance of cefepime in calves.
AB  - The pharmacokinetics of cefepime were studied following intravenous and
      intramuscular administration of 6.5 mg/kg in four female Friesian calves.
      Following single intravenous administration, the serum concentration-time curves
      of cefepime were best fitted using a two-compartment open model. The elimination
      half-life (t(1/2)beta) was 2.38+/-0.16 h, volume of distribution at steady state
      (Vdss) was 0.21 +/- 0.01 L/kg, and total body clearance (ClB) was 1.1 +/- 0.08
      ml/min per kg. Following intramuscular administration, the drug was rapidly
      absorbed with an absorption half-life (t(1/2)ab) of 0.29+/-0.02 h; maximum serum
      concentration (Cmax) of 21.7 +/- 1.1 microg/ml was attained after (Tmax) 1.1 +/-
      0.08 h; and the drug was eliminated with an elimination half-life (t(1/2)el) of
      3.02 +/- 0.18 h. The systemic bioavailability (F) after intramuscular
      administration of cefepime in calves was 95.7% +/- 7.44%. The in vitro serum
      protein-binding tendency was 10.5-16.7%. Following administration by both routes,
      the drug was excreted in high concentrations in urine for 24 h post
      administration.

PMID- 15727294
TI  - Isolation stress in desert sheep and goats and the influence of pretreatment with
      xylazine or sodium betaine.
AB  - We studied some behavioural, clinical, biochemical and haematological variables
      in Desert (Najdi) sheep and goats subjected to the acute stressful stimulus of
      isolation from the flock, and the influence of pretreatment with xylazine (n = 6)
      or sodium betaine (n = 6). The isolation stress resulted in increased
      vocalization and in variable and statistically nonsignificant increases in heart,
      pulse and respiratory rates. Isolation caused significant increases in the plasma
      concentrations of cortisol (from about 35.2 to about 83.8 mmol/L) and glucose
      (from 3.1 to 4.2 mmol/L), and a decrease in that of magnesium (from 0.82 to 0.65
      mmol/L). The endogenous thiocyanate concentration was unaffected. The isolation
      stress also significantly decreased the haematocrit (PCV), and the number of
      lymphocytes, and increased the concentration of haemoglobin. Pretreatment of
      sheep and goats with xylazine at a dose of 0.01 mg/kg by the intravenous route
      significantly ameliorated the effects induced by the stressful stimulus. The
      effects of pretreatment of the two species with sodium betaine (10 mg/kg)
      produced variable and nonsignificant effects. There were no significant
      differences between sheep and goats in the responses to the isolation stress,
      except in vocalization, which was greater in sheep than in goats.

PMID- 15727295
TI  - Environmental benchmarks vs. ecological benchmarks for assessment and monitoring
      in Canada: is there a difference?
AB  - Environmental benchmarks are widely used in Canadian environmental assessment as
      a standard against which to monitor air or water quality in response to human
      activities in the environment. Recent work in Canada has developed the concept of
      ecological benchmarks as a complement to environmental benchmarks. However,
      implementation of ecological benchmarks may be challenging. This paper presents
      an analogy between ecological benchmarks and the more commonly used environmental
      benchmarks, as an attempt to increase understanding and use of ecological
      benchmarks in resource management, assessment, and monitoring. Ecological
      benchmarks, and their corresponding indicators, will be challenging to identify
      and use. However, through the use of the principles of adaptive management,
      effective ecological indicators and benchmarks can be established. Although it is
      essential that ecological benchmarks are site-specific, the analogy and general
      principles outlined here are applicable to assessment and monitoring in any part
      of the world.

PMID- 15727296
TI  - Trace metals: inputs, sedimentation and accumulation in San Vicente Bay, Chile.
AB  - The present study deals with sediment dynamics affecting sediment-associated
      metal distributions in an embayment system experiencing pollution from coastal
      industries. Sedimentary metal content may originate from diagenetic processes of
      foundation rock on the bottom, allochthonous minerals from natural sources, and
      metals from industrial effluents along the coast. The study presents experimental
      estimations of quantities of metals entering the bay in industrial waste-water,
      measurements of metal content in particulate material captured in sediment traps,
      and metals distribution in surface sediments. Quantitative estimations of metals
      entering the system in industrial effluent showed the relation Pb > or = Zn > Cu
      > Cr > or = Ni > Cd. That of metals associated with particulate material from
      traps was Zn > Cr approximately equal to Cu > or = Pb > Ni > Cd and the abundance
      of metals in sediments was Zn > Cr > Cu > Pb > Ni > Cd. Finally, rates of bottom
      sediment accumulation are estimated in relation to the time of residence of water
      in the bay. The experimental data on sedimentation and sediment abundance were
      consistent with field observations on distribution and accumulation at sites of
      major sedimentation in this bay.

PMID- 15727297
TI  - Prediction of extreme ozone levels in Barcelona, Spain.
AB  - Barcelona is one of the most polluted cities in Western Europe, although our
      levels of air pollution are within the World Health Organisation air quality
      guidelines. However, high concentrations of air pollution have not been studied
      yet. Ground ozone levels is a topic of considerable environmental concern, since
      excessive level of ozone are taken as indicative of high pollution. In terms of
      the air quality guidelines ozone levels higher than 100 microg m(-3) can start to
      be health-hazards for human health. Our objective is to report a detailed
      analysis of ozone data exceeding the thresholds established by the air quality
      guidelines. Data analysed were collected in two measurement stations in
      Barcelona, for the reference period 1991--1996. Applying statistical techniques
      commonly used in the analysis of extreme values, mainly the Peak Over Threshold
      method was used for in this study. The analysis reveal that the ozone threshold
      values for the protection of human health has exceeded many times in both
      stations. The estimated return values for 3, 10, and 40 yr exceed the threshold
      value for information to the public of almost once in both stations, also it
      seems to be unlikely that the threshold value for warning to the public will be
      exceeded in 40 yr.

PMID- 15727298
TI  - Meteorological normalisation and non-parametric smoothing for quality assessment
      and trend analysis of tropospheric ozone data.
AB  - Despite extensive efforts to ensure that sampling and installation and
      maintenance of instruments are as efficient as possible when monitoring air
      pollution data, there is still an indisputable need for statistical post
      processing (quality assessment). We examined data on tropospheric ozone and found
      that meteorological normalisation can reveal (i) errors that have not been
      eliminated by established procedures for quality assurance and control of
      collected data, as well as (ii) inaccuracies that may have a detrimental effect
      on the results of statistical tests for temporal trends. Moreover, we observed
      that the quality assessment of collected data could be further strengthened by
      combining meteorological normalisation with non-parametric smoothing techniques
      for seasonal adjustment and detection of sudden shifts in level. Closer
      examination of apparent trends in tropospheric ozone records from EMEP (European
      Monitoring and Evaluation Programme) sites in Finland showed that, even if
      potential raw data errors were taken into account, there was strong evidence of
      upward trends during winter and early spring.

PMID- 15727299
TI  - Enumeration of Legionella pneumophila in cooling tower water systems.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, is known to
      colonise and frequently grow in cooling tower waters. Disease is acquired by
      inhaling aerosol contaminated by legionellae. Determination of the count of
      Legionella pneumophila in cooling tower waters may, therefore, be useful for risk
      assessment. In our survey, 103 water samples from 50 cooling towers were examined
      over a five-year period to indicate the seasonal distribution and the ecology of
      L. pneumophila, as regards temperature and pH. L. pneumophila serogroup 1 was
      found in 44% of the isolated strains, which is primarily responsible for the
      majority of Legionnaires' disease. The large majority of examined towers had
      levels of L. pneumophila in the high-risk category. These cooling towers have
      been linked to many outbreaks of Legionnaires' disease.

PMID- 15727300
TI  - The prevalence of bacterial resistance in clinical, food, water and some
      environmental samples in Southwest Nigeria.
AB  - The resistance pattern and mechanisms of bacterial isolates obtained from
      clinical origin, soil, industrial effluent, orange juice products and drinking
      water were studied using commonly used antibiotics. The microbial load of the
      water samples, industrial effluent and orange juice products were 1.0 x 10(1)
      2.25 x 10(6), 2.15 x 10(5), and 3.5 x 10(4)-2.15 x 10(5) cfu mL(-1),
      respectively. The faecal coliform test revealed that only two out of twenty
      orange juice products had MPN of 2 and 20, the MPN of water ranged from 1-> or =
      1800, while the effluent had MPN of > or = 1800. The bacterial isolates that were
      isolated include E. coli, S. aureus, P. vulgaris, S. marcescens, S. pyogenes, B.
      cereus, B. subtilis, Micrococcus sp., Klebsiella sp., P. aeruginosa, and
      Enterobacter sp. Also, clinical and soil isolates of P. aeruginosa were used in
      the study. Among the eight antibiotics tested for resistance on five strains of
      each bacterium, seven different resistance patterns were observed among the
      bacterial isolates obtained from water, effluent and orange juice products. Among
      the clinical and soil isolates of P. aeruginosa, four multiple-drug resistance
      patterns were obtained. Thirty strains of E. coli and S. aureus were tested for
      beta-lactamase production and fourteen strains, seven each of E. coli and S.
      aureus that had high Minimum Inhibitory Concentration values (MIC) for both
      Amoxycillin and Cloxacillin were positive.

PMID- 15727301
TI  - Distribution of heavy metals in Penaeus semisulcatus from Persian Gulf and
      possible role of metallothionein in their redistribution during storage.
AB  - The study was conducted between January and December 2002. The main objective of
      this study was evaluation of effects of refrigerated storage duration on
      redistribution of three trace elements (Cd, Cu and Zn) in tissues (exoskeleton,
      abdominal muscle and hepatopancreas) of a shrimp species (Penaeus semisulcatus).
      Moreover, the possible roles of metallothionein (a kind of metalloprotein) in
      redistribution of the elements in tissues of the selected species were assessed.
      The specimens were sampled from northwestern part of the Persian Gulf. The
      concentrations of metals in the tissues were measured using Inductively Coupled
      Plasma-Optical Emission Spectrophotometer (ICP-OES). Metallothionein levels were
      determined by Differential Pulse Polarography (DPP) method. pH of the muscle
      samples was also measured in different stages. Different statistical methods were
      used for interpretation of the results. There were no size-dependent differences
      in metal contents of the species. The results were compared with specimens from
      other areas of the world and existing guidelines and limits. Concentrations of
      the metals in the muscle (0.103, 3.418 and 8.977 microg g(-1) wet weight in the
      case of Cd, Cu and Zn, respectively) samples were below the most guidelines for
      human consumption. The results were in general agreement with those obtained by
      some other researchers. There were highly significant differences between sexes
      in Zn and Cu contents. Levels of Zn in females were significantly higher than
      males. The reverse case observed for Cu. The highest mean Cu and Zn
      concentrations (15.939 and 43.394 microg g(-1) wet weight, respectively) were
      found in hepatopancreas samples, but the highest level of Cd (0.790 microg g(-1)
      wet weight) was observed in exoskeleton. There were significant differences
      between the fresh and refrigerated samples from accumulation of Cd and Zn in
      tissues point of view, which can be attributed to the metal binding properties of
      metallothioneins as well as their degradation during the storage.

PMID- 15727302
TI  - Trace elements accumulation in edible tissues of five sturgeon species from the
      Caspian Sea.
AB  - This study is focused on twenty trace elements (Ag, Ba, Bi, Cd, Co, Cr, Cs, Cu,
      Ga, In, Mn, Mo, Pb, Rb, Sb, Sn, Sr, Ti, V, Zn) accumulation in muscles of five
      sturgeon species (Acipenser guldenstaedti, A. persicus, A. nudiventris, A.
      stellatus and Huso huso) from the southern part of the Caspian Sea. Moreover the
      relationships between some biological characteristics and the levels of the
      selected elements as well as inter-elemental relationships were assessed. The
      samples (10 specimens for each the five species) were collected from two
      important sturgeon fishery zones located in the Iranian part of the Sea in 2002.
      Concentrations of the elements were determined using ICP-MS. Only in the case of
      Cs could significant differences between two selected sampling areas be detected.
      There were significant differences in levels of Co, Ga, Rb, Sn, Ti, Pb and Bi in
      muscles of the species. Only in the case of Cd weight related differences among
      the species were found. The significant length dependent relationships were
      observed for Ga and Ba. Patterns of elements accumulation were assessed by
      statistical methods and compared to the other researches. In all the cases, the
      amounts of toxic trace elements (Cd, Cu, Pb and Zn) were markedly below the
      international guidelines for human consumption.

PMID- 15727303
TI  - Eight nonnative plants in western Oregon forests: associations with environment
      and management.
AB  - Nonnative plants have tremendous ecological and economic impacts on plant
      communities globally, but comprehensive data on the distribution and ecological
      relationships of individual species is often scarce or nonexistent. The objective
      of this study was to assess the influence of vegetation type, climate,
      topography, and management history on the distribution and abundance of eight
      selected nonnative plant taxa in forests in western Oregon. These eight taxa were
      selected as being reliably detected by a multi-resource inventory of 1127
      systematically-placed plots on non-federal forest lands from 1995 to 1997 by the
      USFS Forest Inventory and Analysis (FIA) program. One or more of the eight
      nonnative taxa studied were found on 20% of the sampled subplots in the study
      area, but relatively few stands were dominated by them. Overall abundance of
      nonnative taxa was likely much greater, because few composites and graminoids
      were identified to species in this general-purpose inventory. Distribution of
      most taxa was more closely associated with low density of overstory trees than
      with climate. Nonnative taxa were significantly more abundant in stands that had
      been recently clearcut or thinned than in stands that had not. Frequencies of
      several taxa decreased with elevation, which may reflect proximity to source
      populations and intensive land use rather than any climatic constraints. Although
      the greatest potential for displacement of native forest species appears to be in
      early-successional communities, the potential for spread of some shade-tolerant
      evergreen shrubs also seems high.

PMID- 15727304
TI  - The condition of coral reefs in South Florida (2000) using Coral disease and
      bleaching as indicators.
AB  - The destruction of coral reef habitats has occurred at unprecedented levels
      during the last three decades. Coral disease and bleaching in the Caribbean and
      South Florida have caused extensive coral mortality with limited recovery, often
      coral reefs are being replaced with turf algae. Acroporids were once dominant
      corals and have diminished to the state where they are being considered as
      endangered species. Our survey assessed the condition of reef corals throughout
      South Florida. A probability-based design produced unbiased estimates of the
      spatial extent of ecological condition, measured as the absence or presence and
      frequency or prevalence of coral diseases and bleaching intensity over large
      geographic regions. This approach allowed us to calculate a quantifiable level of
      uncertainty. Coral condition was estimated for 4100 hectares (ha) (or 41.0 km2)
      of coral reefs in South Florida, including reefs in the Florida Keys National
      Marine Sanctuary (FKNMS), New Grounds, Dry Tortugas National Park (DTNP), and
      Biscayne National Park (BNP). The absence or presence of coral disease, 'causal'
      coral bleaching, partial bleaching and coral paling were not good indicators of
      overall coral condition. It was more useful to report the prevalence of anomalies
      that indicated a compromised condition at both the population and community
      levels. For example, 79% of the area in South Florida had less than 6% of the
      coral colonies diseased, whereas only 2.2% (97.15 ha) of the sampled area had a
      maximum prevalence of 13% diseased coral colonies at any single location. The
      usefulness of 'causal bleaching' might be more important when considering the
      prevalence of each of the three different states at a single location. For
      example, paling was observed over the entire area, whereas bleaching and partial
      bleaching occurred at 19 and 41% of the area, respectively. An index for coral
      reef condition might integrate the prevalence and species affected by each
      bleaching state at individual locations. By establishing these baselines, future
      surveys can examine changes and trends in the spatial distribution of coral
      conditions in South Florida and able to score the reefs as to their health
      status.

PMID- 15727305
TI  - The performance evaluation of WinOSPM model for urban street canyons of Nantes in
      France.
AB  - Air quality modelling is primarily the quantative approach. It is more difficult
      as it demands input data accuracy, uncertainties and the efficient methodologies
      to judge the extent of models accuracy. As a result, model validation has to be
      regarded as an integral part of the modelling process. Furthermore, models are
      often validated on a limited number of testcases therefore, appropriate
      evaluation procedure must be implemented to ensure these models will be
      applicable for various conditions. The study presented here was carried out to
      evaluate the WinOSPM (Preliminary version of windows based Operational Street
      Pollution Model) for air pollutants viz. CO, NO, NO2, NOx and C6H6 for three
      street canyons of Nantes (France) and for the three base years 1999, 2000, and
      2001. Each street canyon selected for this study has typical and unidentical
      features. The rue de Strasbourg and Boulevard Victor Hugo have many building
      exceptions whereas rue Crebillon has not any. Application of the model above to
      the three street canyons revealed that WinOSPM could be used in the case when
      measurements are not available. This was justified from the results at rue
      Crebillon. The special interest was in the benzene modelled values as its content
      in fuel has been targeted to reduce to 1% for the years 2000 and onwards (from
      its 5% until the year 1999). The 50 to 70% reduction in the benzene
      concentrations is found for both the years i.e. in 2000 and 2001. This has
      further justified that air quality models are useful and interesting tools in
      optimising emission reduction strategies. Moreover, it is also the new pollutant
      added to the measurement campaign of Air Pays de la Loire (APL) for the city of
      Nantes. For benzene weekly averages are estimated from the hourly-modelled values
      for all the streets and compared with that of measurements. They are found in
      excellent agreement with each other's. For other pollutants annual means and
      percentiles were compared. The statistical analysis was done to evaluate the
      models performance using index of agreement and correlation coefficient. The
      index of agreement (d) and correlation coefficient (r) for all the streets show
      that estimated concentration levels are in good agreement with that of
      measurements. From the index of agreements, it can be inferred that model has
      very less potential for errors. The model's sensitivity to building-exceptions
      was also tested for the rue de Strasbourg. Results did not reflect this feature
      very well. It is perceived that the influence of this feature might have been
      suppressed in averaging the annual hourly values. This influence is apparently
      seen in hourly average time series variations. Finally, WinOSPM model was found a
      simple but very useful model. It could very well represent the detailed flow and
      dispersion conditions in urban streets.

PMID- 15727306
TI  - Nutrient transfer by Runoff from sewage sludge amended soil under simulated
      rainfall.
AB  - Wastewater sludges are used in agriculture as soil amendment and fertilizer, with
      regard to their organic matter and nutrient content. However, availability of
      nitrogen and phosphorus from sludge-amended soils and their transfer in runoff
      may lead to eutrophication of downstream surface water. The aim of this study is
      to establish and compare the effect of two different sludges on these transfers:
      an anaerobically digested and thermically stabilised sludge (Seine-Aval treatment
      plant, sludge no. 1), and a limed sludge (Saint-Quentin treatment plant, sludge
      no. 2). Experiments were performed on 12 sloping micro-plots (1 m x 1 m)
      submitted to sludge spreading and controlled rainfall simulation. Runoff water
      was sampled and analysed for concentrations in nitrogen species and phosphorus.
      Results show that spreading of sludge no. 1 increased both ammonium nitrogen
      (mean of 1.1 mg L(-1) N-NH4 vs. 0.2 mg L(-1) N-NH4 for control micro-plots) and
      particulate phosphorus concentrations (mean of 2 mg L(-1) P vs. 1.1 mg L(-1) P
      for control micro-plots) in runoff water. On the other hand, sludge no. 2 did not
      induce any significant effect on nutrient concentrations in runoff. These results
      are related to chemical composition and physical treatment of sludges. This study
      underlines the existence of a short-term risk of nutrient mobilisation by runoff
      after sludge spreading on soil, and the need to check precisely the impact of
      this practice on water quality.

PMID- 15727307
TI  - Sequential fractionation of phosphorus in lake sediments of Northern Greece.
AB  - The amounts and forms of potentially mobile P in surface sediments from two
      lakes, Volvi and Koronia, located in Northern Greece were evaluated using a
      sequential chemical extraction. Five sedimentary P reservoirs were separately
      quantified: loosely sorbed P (NH4Cl-P); iron associated P (BD-P); calcium bound P
      (HCl-P); metal oxide bound P (NaOH-P) and residual P (organic and refractory P).
      Samples were taken in two seasons and the average concentration of the fractions
      of phosphorus were calculated. The results indicated that the TP content and
      chemically extractable phosphorus in the sediments of Koronia Lake were higher
      than those of Volvi Lake. Sediment TP was also strongly and positively correlated
      with sediment Fe. Fine-sized sediments exhibited significantly higher
      concentrations for both lakes than the sand fraction. The P in the surface
      sediment mainly consisted of HCl-P and Res-P, while NH4Cl-P and BD-P only
      constituted a minor part. The rank order of the different P extracts was the same
      for the two lakes and was Residual-P > HCl-P > NaOH-P > BD-P > NH4Cl-P.

PMID- 15727308
TI  - Air monitoring of persistent organic pollutants in the Great Lakes: IADN vs.
      AEOLOS.
AB  - When designing a monitoring campaign, one has to consider many factors in the
      decision to perform a long-term synoptic monitoring program or a short-term
      intensive study. Each has its own advantages and disadvantages. This paper
      compares and contrasts the information obtained from two studies conducted on the
      Laurentian Great Lakes. One, the Integrated Atmospheric Deposition Network
      (IADN), is a long-term synoptic monitoring study and the other, the Atmospheric
      Exchange Over Lakes and Oceans (AEOLOS), was a short-term intensive study. The
      advantages of long-term synoptic monitoring programs are providing greater
      spatial information, the relative influence of long and short-range transport on
      the regional background, gross loadings representative of the majority of each
      lake and long-term temporal trends. Short-term intensive studies provide more
      information on the processes governing sources, transport and deposition, such as
      the urban/industrial influence on adjacent large water bodies, specific sources
      to an urban/industrial area and short-term fluctuations in concentrations due to
      meteorology, source strength and photochemical reactions. Using information
      provided by both the IADN and AEOLOS studies, areas of urban influence are
      predicted for each of the five Great Lakes.

PMID- 15727310
TI  - Comparison of data from two vegetation monitoring methods in semi-natural
      grasslands.
AB  - Two vegetation-monitoring methods were compared: subplot frequency analysis (SF)
      and visual estimation of percentage cover (VE). Two independent observers
      collected data from two semi-natural, species-rich grasslands on three different
      occasions during the growth-season. During the last data collection period,
      survey times were also recorded. The two different data sets from the two methods
      were compared using partial Redundancy Analyses. The purpose of the comparison
      was to identify the method that explains most of the relevant variation in
      biodiversity-monitoring (inter- and intra-site variation), and the variation
      irrelevant when evaluating data (systematic inter-observer variation and
      variation due to phenological changes). Compared with VE data, more variation in
      SF data could be explained by spatial variables, while less variation depended on
      the observer and time of year surveyed. SF also found more species per plot but
      took on average five times longer to complete than VE. In conclusion, the
      different methods are suitable for different purposes: SF is more suitable for
      purposes demanding high accuracy and high precision, such as long-term
      biodiversity-monitoring when the identification of small changes has high
      priority, while VE might be more suitable for a one-time mapping of a large area.

PMID- 15727309
TI  - Aliphatic and polycyclic aromatic hydrocarbons in sediments of Kaohsiung Harbour
      and Adjacent Coast, Taiwan.
AB  - Surficial sediment samples collected from Kaohsiung Harbour and its nearby coast
      were analyzed for aliphatic hydrocarbons and parent polycyclic aromatic
      hydrocarbons (PAHs). According to our results, the average total concentrations
      of n-alkanes (n-C12 to C35) and aromatics (15 PAHs) were 4.33 microg g(-1) dry
      weight (ranged 0.46-22.60) and 0.59 microg g(-1) dry weight (ranged 0.09-1.75),
      respectively. The highest concentrations of aliphatic and aromatic hydrocarbons
      were recorded in stations near the estuaries of Qianzhen River and Love River,
      respectively. Aliphatic hydrocarbons in the samples indicate that there has been
      significant non-petrogenic, possibly terrestrial, contribution in the sediment of
      the open coast of Kaohsiung Harbour and that there has been dominant contribution
      from petrogenic sources in the sediment of the inner harbour. PAHs, detected in
      the samples, however, indicated a higher pyrolytic contribution in open-coast
      samples and a higher petrogenic contribution in the inner harbour. Overall,
      sediment concentrations of total alkanes in this study were comparable to those
      found in Victoria Harbour, Hong Kong and are higher than those found in Xiamen
      Harbour, China. Concentrations of total PAHs in inner Kaohsiung Harbour sediments
      were relatively lower than those found in Victoria Harbour, Hong Kong and Xiamen
      Harbour, China, but comparable to those found in Hsin-ta Harbour, Taiwan and
      Incheon Harbour, Korea. In comparison with several effect-based sediment quality
      guidelines, most PAH concentrations found in samples taken from inner harbour
      stations exceeded the Threshold Effect Level of Florida indicating a slight
      possibility of adverse effects.

PMID- 15727311
TI  - Evaluation of air pollution phytotoxicity downwind of a phosphate fertilizer
      factory in India.
AB  - The effects of air pollution on plants downwind of a fertilizer factory at
      Udaipur, India, were studied using three woody perennials. Seedlings of these
      species including a shrub (Carissa carandas L.), a leguminous avenue tree (Cassia
      fistula L.) and a fruit tree (Psidium guajava L.) were grown in earthen pots at
      different study sites receiving varying levels of air pollution input. Changes in
      plant growth, morphological characteristics, photosynthetic pigment, ascorbic
      acid, N and S contents and in dry matter allocation were considered in relation
      to the status of ambient air quality. Observations with these parameters have
      indicated that the ambient air around the factory contained pollutants at
      phytotoxic levels. Plant height, basal diameter, conopy area, leaf area and
      chlorophyll, ascorbic acid and foliar-N concentrations decreased with increasing
      pollution load. However, foliar-S increased slightly at polluted sites. Air
      pollution load around the factory have also altered the biomass allocation.
      Root:shoot ratios increased in C. fistula and P. guajava at polluted sites. In
      contrast, for C. carandas the above ground parts, where foliage assumed
      predominance showed precedence over the root growth. This species responded
      characteristically to air pollution stress by allocating more of its
      photosynthate towards leaf production and shoot growth.

PMID- 15727312
TI  - Combined use of Rapid Bioassessment Protocols and Sediment Quality Triad to
      assess stream quality.
AB  - Physical, chemical and biological conditions at five stations on a small
      southeastern stream were evaluated using the Rapid Bioassessment Protocols (RBP)
      and the Sediment Quality Triad (SQT) to assess potential biological impacts of a
      municipal wastewater treatment facility (WWTF) on downstream resources. Physical
      habitat, benthic macroinvertebrates and fish assemblages were impaired at
      Stations 1 and 2 (upstream of the WWTF), suggesting that the degraded physical
      habitat was adversely impacting the fish and benthic populations. The SQT also
      demonstrated that Stations 1 and 2 were degraded, but the factors responsible for
      the impaired conditions were attributed to the elevated concentrations of
      polycylclic aromatic hydrocarbons (PAHs) and metals (Mn, Pb) in the sediments.
      The source of contaminants to the upper reaches of the stream appears to be storm
      water runoff from the city center. Increased discharge and stabilized base flow
      contributed by the WWTF appeared to benefit the physically-altered stream system.
      Although the two assessment procedures demonstrated biological impairment at the
      upstream stations, the environmental factors identified as being responsible for
      the impairment were different: the RBP provided insight into contributions
      associated with the physical habitat and the SQT contributed information on
      contaminants and sediment quality. Both procedures are important in the
      identification of physical and chemical factors responsible for environmental
      impairment and together they provide information critical to the development of
      appropriate management options for mitigation.

PMID- 15727313
TI  - Working together toward common goals.

PMID- 15727314
TI  - Who's at fault?

PMID- 15727315
TI  - Dr. Lau responds to CRANIO's October '04 Concepts Editorial.

PMID- 15727316
TI  - An investigation into the relationship between noncarious cervical lesions and
      premature contacts.
AB  - The aim of the present study was to investigate the relationship between
      noncarious cervical lesions (NCCL) and dental premature contacts (PC). Following
      examination of 1,974 teeth from 77 patients referred to the Department of Oral
      Medicine, Faculty of Dentistry, Mashad University of Medical Science, Iran, a
      total of 167 teeth were identified to have the criteria set for noncarious
      cervical lesions (regarded as NCCL group). Also, 167 teeth exhibiting no such
      lesions were selected randomly from the same population (regarded as control
      group). The results indicated that within the NCCL group, the frequency of
      noncarious cervical lesions differed significantly among the various teeth; the
      first premolar teeth showed the greatest number of cervical lesions, followed by
      the canine teeth, and the second molar teeth had the least number of lesions. A
      similar trend was detected in the total number of premature contacts among the
      seven types of teeth. The results revealed a highly significant and positive
      correlation between the incidence of NCCL and the PC. The NCCL group and the
      control group differed significantly in the number of premature contacts in
      centric relation (CR) and working side, but not in balancing and protrusion.

PMID- 15727317
TI  - Relationship between habitual occlusal position and flat bite plane induced
      occlusal position in volunteers with and without temporomandibular joint sounds.
AB  - The aim of this study was to assess whether temporomandibular joint (TMJ) sounds
      are associated with the difference between the habitual occlusal position (HOP)
      and the bite plane induced occlusal position (BPOP). Fifteen dental technician
      school students who had complete natural dentition, normal occlusion and who
      exhibited TMJ sounds were compared with fifteen healthy control subjects. HOP was
      recorded by voluntary jaw closing while in an upright position, and BPOP was
      recorded after wearing an anterior bite plane for a short period of time. Three
      interocclusal records were obtained in both positions with a vinyl polysiloxane
      material, and the recorded maxillomandibular relations were analyzed three
      dimensionally and compared. Subjects with TMJ sounds had statistically larger
      differences between HOP and BPOP than controls (p<.05). Within this study
      population, an association was found between TMJ sounds and the difference
      between HOP and BPOP.

PMID- 15727319
TI  - A new approach to improve TMJ morphological information from plain film
      radiographs.
AB  - The hard tissues of the temporomandibular joint (TMJ) can be assessed through
      radiographic imaging to provide information to assist in diagnosis and treatment.
      However, the quality of information gathered from such imaging is often less than
      desired due to the small size of the TMJ, the widely varying fossa and condylar
      morphology, and the surrounding dense osseous structures. These make a clear and
      undistorted radiographic image of the hard tissue of the joint technically
      difficult. It is postulated that, if the degree of inaccuracy of a given
      radiograph is known quantitatively and taken into account, the clinician will be
      able to make a better informed qualitative assessment of TMJ morphology. The aim
      of this study is: 1. to improve the qualitative information that can be acquired
      from routine clinical plain film radiographs of the TMJ; 2. to use quantitative
      data to test the novel Neural Network (NN) model; and 3. to statistically show
      the discrepancies between routine radiographic images and the actual joint.
      Linear measurements of excised TMJs and their radiographic images were used to
      train a multilayer perceptron (MP) type NN model to predict joint dimensions more
      accurately. Such a neural network, developed using a statistical software package
      such as SPSS (SPSS, Inc. Chicago, IL), functions as a computer software program
      and predicts joint dimensions with increased accuracy when radiographic
      measurements are entered into the program. The NN model described here predicts
      the actual linear distances of the TMJ more closely than radiographic
      measurements and is more reliable in assessing the TMJ morphology.

PMID- 15727318
TI  - Correlation between disk morphology on MRI and time curves using electronic
      axiography.
AB  - This retrospective series was intended to determine whether morphological disk
      findings in open and closed mouth magnetic resonance imaging (MRI) may be
      correlated with the time curves in axiography. In this series, 45
      temporomandibular joints of 33 patients were subjected to a retrospective
      evaluation. Magnetic resonance images obtained with closed and open mouth and
      joint movements assessed by electronic axiography were analyzed. Disk morphology
      in MRI was classified as normal, partly flattened, partly thickened, or
      completely thickened. For the axiographic tracings, time curves of the free
      movements of the respective joint were developed and evaluated. Data obtained
      were analyzed for any potential correlation using scatter plots and discriminance
      analysis. No correlation between these data was found suggesting that the
      axiographic time curves do not provide for any conclusions with regard to disk
      morphology. Apart from patient history and a thorough clinical evaluation,
      recording of jaw movements, but also using MRI continues to be of particular
      value in the diagnostic assessment of anterior disk displacement.

PMID- 15727321
TI  - The effect of condyle fossa relationships on head posture.
AB  - Although it is commonly accepted that there is an interrelationship between the
      temporomandibular joint (TMJ) and head posture, few, if any, previous studies
      have quantified this effect. The purpose of this study is to quantify the effect
      of a change in the condyle fossa relationship of symptomatic temporomandibular
      joints on head posture. Charts of 51 patients (N=10 men and N=41 women) with
      symptomatic TMJ pathology were reviewed. The condyle fossa relationships were
      measured pre- and posttreatment using sagittal corrected hypocycloidal
      tomography. The amount of slant between the shoulder and external auditory meatus
      (EAM) was measured in pre- and posttreatment photographs as an indicator of
      forward head posture; less slant indicates better posture. Subjects ranged in age
      from 13-74 years (mean=43.1) and had been treated for an average of 5 months.
      Comparisons with pre-treatment measures showed that after treatment, the amount
      of retrodiskal space was significantly increased by an average of 1.67 mm on the
      left side (t=-10.11, p<0.0001) and 1.92 mm on the right (t=-9.62, p<0.0001).
      Comparisons also showed that after treatment, the amount of slant between the
      shoulder and EAM decreased by 4.43 inches on average which was also significant
      (t=13.08, p<0.0001). Improvement in the condyle fossa relationship was related to
      decreased forward head posture. This suggests that optimizing mandibular condyle
      position should be considered in the management of forward head posture (adaptive
      posture).

PMID- 15727320
TI  - The effect of bilateral lingual nerve anesthesia and increased occlusal vertical
      dimension on the onset of swallowing in adult males.
AB  - The present study attempts to determine whether the onset of swallowing is
      affected by bilateral lingual and inferior alveolar nerve anesthesia and by
      raising the occlusal vertical dimension by wearing an occlusal bite plate. Twenty
      young male volunteers were selected and asked to chew and swallow corned beef and
      a corned beef and liquid mixture in their usual manner before and after
      modifications were made. Oral and pharyngeal swallowing was investigated using
      videofluoroscopic examination in the lateral plane. Eight objective indicators,
      including oral containment time, swallowing threshold, and pharynx-to-swallow
      intervals were estimated. Oral containment time, total sequence duration, total
      number of chews, and total number of swallows of the two test foods were
      significantly different before and after the modifications. Individual pharynx-to
      swallow intervals also varied. The results indicate that modification of the
      masticatory condition affects the onset of swallowing and that changes in the
      onset varied among the participants.

PMID- 15727322
TI  - Evaluation of cervical spine posture after functional therapy with FR-2: a
      longitudinal study.
AB  - The authors compared postural changes produced in 20 Caucasian female children
      treated with the Frankel Functional Regulator appliance (FR-2) (Frankel
      Industries, Morangis Cedex, France) using cephalometric tracings and comparing
      the tracings to 20 untreated Class II controls from the University of Chieti.
      Each patient in the study group was treated for exactly two years by the same
      operator using the FR-2 appliance and a standardized design and clinical
      technique, including prefunctional orthodontics where indicated. The average
      starting age was 8.4 yrs. (SD+/-2.1). At the end of the therapy, the average age
      was 10.3 yrs. (SD+/-2.4). Two teleradiographs were made of each patient: the
      first one at the beginning of treatment and the second one after six months. The
      radiographs were taken with the subjects standing in the ortho-position with no
      ear rods in the cephalostat; mirror position was carried out. In order to detect
      errors due to landmark identification, duplicate measurements were made using ten
      radiographs, and the error variance was calculated using Dahlberg's formula.
      Thirty-seven variables were studied. The cervical lordosis angle (CVT/EVT) was
      significantly higher in the study group as compared to the control group (p<0.05)
      at the end of treatment, probably due to a significant backward inclination of
      the upper segment of the cervical column (OPTNer and CVTNer) in the treated group
      (p<0.001 and p<0.01) from pre- to posttreatment. There was no significant change
      in the lower segment of the cervical column inclination (EVT/Ver). The changes
      resulted in a weak association in the multiple regression model to an increasing
      of maxillary base length and mandibular protrusion (R2=0.272; p<0.05). Other
      variables in the multiple regression were not significant.

PMID- 15727323
TI  - The effects of seasonal changes on temporomandibular disorders.
AB  - The aim of our study was the evaluation of seasonal influences on development and
      evolution of temporomandibular disorders (TMD). In a retrospective study based on
      data from 1997 and 1998, we analyzed the monthly number of patients at the
      Department of Prosthodontics. The total number of first time examinations during
      these two years was 11,747. Nine hundred and sixty-one (961) patients showed
      symptoms frequently found in TMD. These patients were submitted to a special TMD
      diagnosis based on the criteria of a validated craniomandibular index
      questionnaire. In 568 patients (group A1), a TMD was confirmed, in the other 393
      patients (group A2), the disorder could not be confirmed. Dividing up the numbers
      of patients into summer and winter half years, we found statistically significant
      relationships between patient numbers and season in TMD patients (A1) as well as
      in all patients (group B). The distribution of the monthly numbers of TMD
      patients with its maximum in winter, however, was characteristically different
      from that of all patients with the maximum in summer. The number of TMD patients
      per month was significantly correlated to the mean daily sunshine duration per
      month. Parallels could be drawn to seasonal variations of symptoms in Seasonal
      Affective Disorders (SAD). As the mechanisms which influence the emergence of
      psychologically impacted disease in TMD patients might be comparable to SAD, we
      propose that a similar therapy may be applied.

PMID- 15727324
TI  - Maxillofacial and dental manifestations in a patient with mandibulo-acral
      dysplasia.
AB  - Mandibulo-acral dysplasia (MAD) is a rare condition characterized by mandibular
      hypoplasia, acroosteolysis, delayed cranial suture closure, hypoplastic
      clavicles, stiff joints, dental crowding, atrophy of the skin of the hands and
      feet, progeroid facial appearance, alopecia and short stature. This report
      presents a patient with MAD, suffering from difficulty in mastication and speech,
      together with limited lip closure and aesthetic problems related to the clinical
      outcomes of the syndrome. The aim of reporting this case is to detail the first
      widely determined dental and maxillofacial abnormalities of a rare syndrome,
      mandibulo-acral dysplasia, and to contribute to the data regarding the etiology
      of consanguinity.

PMID- 15727325
TI  - Relationship between home literacy environment and reading achievement in
      children with reading disabilities.
AB  - Past research has indicated that a significant relationship exists between young
      children's early home literacy environment and their reading-related skills.
      However, this relationship has rarely been investigated among older children with
      reading disabilities (RD). In the present study, the relationship between parent
      and child home literacy activities and children's academic functioning was
      investigated with a sample of 65 elementary-age children with RD. The results
      indicated that children's home literacy activities were not significantly related
      to any of their academic abilities, whereas parents' home literacy activities
      were significantly related to children's passage comprehension and spelling
      scores. However, relationships between home literacy environment and reading may
      be different for children with and without RD.

PMID- 15727326
TI  - Relationships among rapid digit naming, phonological processing, motor
      automaticity, and speech perception in poor, average, and good readers and
      spellers.
AB  - In this article, we explore the relationship between rapid automatized naming
      (RAN) and other cognitive processes among below-average, average, and above
      average readers and spellers. Nonsense word reading, phonological awareness, RAN,
      automaticity of balance, speech perception, and verbal short-term and working
      memory were measured. Factor analysis revealed a 3-component structure. The first
      component included phonological processing tasks, RAN, and motor balance. The
      second component included verbal short-term and working memory tasks. Speech
      perception loaded strongly as a third component, associated negatively with RAN.
      The phonological processing tests correlated most strongly with reading ability
      and uniquely discriminated average from below- and above-average readers in terms
      of word reading, reading comprehension, and spelling. On word reading,
      comprehension, and spelling, RAN discriminated only the below-average group from
      the average performers. Verbal memory, as assessed by word list recall,
      additionally discriminated the below-average group from the average group on
      spelling performance. Motor balance and speech perception did not discriminate
      average from above- or below-average performers. In regression analyses,
      phonological processing measures predicted word reading and comprehension, and
      both phonological processing and RAN predicted spelling.

PMID- 15727327
TI  - Evaluation of the double-deficit hypothesis in college students referred for
      learning difficulties.
AB  - The present study explored the double-deficit hypothesis (DDH) in a sample of 146
      college students with and without reading disabilities (RD). The results
      indicated that although both phonological awareness (PA) and visual naming speed
      (VNS) contributed to performance on measures of decoding and comprehension, their
      relative contribution was influenced both by the nature of the stimulus (word vs.
      nonword vs. text) and by the conditions of the task (timed vs. untimed). Similar
      results were obtained using an individual differences approach, or when between
      group comparisons were made of individuals with deficits in PA or VNS. The
      relative representation of DDH subgroups in groups of adults with RD varied based
      on the classification criteria used to define RD. These results support the DDH,
      extend its applicability to adults, and have implications for diagnostic decision
      making.

PMID- 15727328
TI  - Social information processing and emotional understanding in children with LD.
AB  - The present study aimed to comprehensively examine social cognition processes in
      children with and without learning disabilities (LD), focusing on social
      information processing (SIP) and complex emotional understanding capabilities
      such as understanding complex, mixed, and hidden emotions. Participants were 50
      children with LD (age range 9.4-12.7; 35 boys, 15 girls) and 50 children without
      LD matched on grade, age, and gender. Children analyzed 4 social vignettes using
      Dodge's SIP model and completed 2 emotional recognition tasks (pictures and
      stories) and 4 emotional knowledge tasks, such as providing definitions and
      examples for 5 emotions (e.g., loneliness, pride, embarrassment). Study results
      demonstrated that children with LD had major difficulties in SIP processes and
      consistent difficulties with the different tasks in the understanding of complex
      emotions and in higher emotional understanding capabilities, such as
      understanding that 2 conflicting emotions (love and hate) can be simultaneously
      experienced. We discuss the implications of such difficulties for the
      understanding of social competence in children with LD as well as their
      implications for social skills intervention.

PMID- 15727329
TI  - Teachers with LD: Ongoing negotiations with discourses of disability.
AB  - The purpose of this study is to examine how 4 teachers with learning disabilities
      (LD) negotiate multiple, complex, and sometimes contradictory discourses of
      disabilities in constructing their own understandings of LD. We chose to study
      teachers with LD because of their unique access to at least 3 different sources
      of knowledge about LD: (a) professional discourses on disability, (b) mainstream
      cultural messages about LD, and (c) insights gained from their own life
      experience. We drew on aspects of critical discourse analysis and narrative
      inquiry for this investigation. Our findings indicate that participants draw on
      these discourses and on their teaching experience in various and complex ways to
      construct meaning about LD. In some instances, participants use the dominant
      discourses; at other times, they work to subvert these meanings. Yet,
      paradoxically, whether speaking with or against these meanings, their voices are
      inescapably engaging with authoritative discourses and cultural scripts
      surrounding disability.

PMID- 15727330
TI  - Use of grade-based norms versus age-based norms in psychoeducational assessment
      for a college population.
AB  - Considerable discussion has occurred about the most appropriate methods for
      diagnosing learning disabilities (LD) in postsecondary students. Two of the many
      areas of controversy that have emerged include the appropriate diagnostic
      criteria to use and the appropriate referent group. A review of previous court
      cases demonstrates that the issue of whether to compare an individual to the
      general population or to a smaller referent population has not been adequately
      clarified. Furthermore, few empirical studies have examined the impact of
      choosing different referent groups on the likelihood that one will be diagnosed
      with LD. Therefore, this correlational study described the levels of agreement
      between three diagnostic models of LD, using both age- and grade-based norms to
      represent two referent groups for each of the three models. The sample included
      155 postsecondary students referred for testing due to academic difficulties. The
      findings indicated that in two of the three models tested, comparing individuals
      to their grade-matched peers (i.e., using grade-based norms) resulted in more LD
      diagnoses than comparing individuals to their age-matched peers (i.e., age-based
      norms).

PMID- 15727331
TI  - ADHD and dyscalculia: Evidence for independent familial transmission.
AB  - The familial relationship between dyscalculia and attention-deficit/hyperactivity
      disorder (ADHD) was assessed. We conducted a familial risk analysis using
      probands with and without ADHD of both genders and their first-degree relatives.
      Participants were assessed with structured diagnostic interviews and a cognitive
      test battery. We found elevated rates of ADHD in relatives of both ADHD proband
      groups, regardless of dyscalculia status, and elevated rates of dyscalculia in
      relatives of probands with dyscalculia, irrespective of ADHD status. There was no
      evidence for cosegregation or assortative mating. Our findings support the
      hypothesis that ADHD and dyscalculia are independently transmitted in families
      and are etiologically distinct. These results reinforce the current nosological
      approach to these disorders and underscore the need for separate identification
      and treatment strategies for children with both conditions.

PMID- 15727332
TI  - [What are the stated pharmacokinetic parameters?].

PMID- 15727333
TI  - [Endocannabinoid and endocannabinoid receptor antagonists].

PMID- 15727334
TI  - [Tuberculosis. An old infectious disease with new problems].

PMID- 15727335
TI  - [Red vine leaf extract (AX 195) for chronic venous insufficiency].

PMID- 15727336
TI  - [Cobalamin--a critical nutritive element in old age].

PMID- 15727337
TI  - I don't believe in the tooth fairy, either.

PMID- 15727338
TI  - Any action on healthcare?

PMID- 15727339
TI  - Step 4: Weighing offers.

PMID- 15727340
TI  - My patient gave me a second chance.

PMID- 15727341
TI  - Expense survey: what to spend, what to cut.

PMID- 15727342
TI  - Pay for performance: a double-edged sword.

PMID- 15727343
TI  - Doctors and EHRs.

PMID- 15727344
TI  - Put a dollar value on employee benefits.

PMID- 15727345
TI  - Disclosing contingency fees.

PMID- 15727346
TI  - Overseas transcription: I say no!

PMID- 15727347
TI  - Being a specialist GP.

PMID- 15727348
TI  - The future of general practice.

PMID- 15727349
TI  - Victorian polio service.

PMID- 15727350
TI  - This summer, start a small social revolution.

PMID- 15727352
TI  - Teen pregnancy--a program for awareness and health education.
AB  - BACKGROUND: Baby Think It Over is a health program that provides Perth
      adolescents in metropolitan schools with a 'virtual' parenting experience using
      an infant simulation program. Baby Think It Over seeks to modify attitudes toward
      teen pregnancy and parenting and to delay pregnancy until the participants have a
      better understanding of the demands and responsibilities of caring for an infant.
      At the same time, this program provides an opportunity to introduce adolescents
      to health services within their community with a particular focus on general
      practice. OBJECTIVE: This article describes the methodology and qualitative
      assessment of the program, examines some outcomes associated with its uptake and
      lessons learnt in its implementation. DISCUSSION: The program demonstrates that
      divisions of general practice can work together with schools to deliver
      innovative programs. The value of projects like this is in the community
      partnerships and social capital that they build across the health and education
      sector.

PMID- 15727351
TI  - Clockwork Young People's Health Service.

PMID- 15727353
TI  - Men's health, GPs, and 'GPs4Men'.
AB  - BACKGROUND: Men have poorer health outcomes than women in many areas,
      particularly cardiovascular health, workplace health and safety, and mental
      health. They tend to present later with health problems, attend general
      practitioners less frequently; and when they do present, have shorter
      consultations and are less likely to attend for preventive health checks.
      OBJECTIVE: This article discusses issues impacting on men's health, the GPs4Men
      network, and future directions for improving men's health. DISCUSSION: GPs4Men,
      the Australian GPs Network for Men's Health, was formed in response to lack of
      policy and funding for men's health. The mission of GPs4Men is to improve the
      health of men, both nationally and individually, via greater community engagement
      by GPs, increased GP participation in population health activities for men,
      increased professional development in men's health, and the promotion of research
      into men's health. Collaboration between key bodies including The Royal
      Australian College of General Practitioners, divisions of general practice, other
      medical and health organisations, and governments is required to address the
      problems in men's health.

PMID- 15727354
TI  - 'Yarning for better health'. Improving the health of an Aboriginal and Torres
      Strait Islander population.
AB  - BACKGROUND: For over 2 years--as part of a broader strategy to address the health
      disadvantages in the Aboriginal and Torres Strait Islander population--Brisbane
      South Division of General Practice (BSDGP) has been involved in providing
      community health education to the local indigenous community. OBJECTIVE: This
      article discusses the 'Yarning for better health' program. DISCUSSION: The
      program aims to improve the local indigenous population's knowledge of health
      issues, particularly preventive health, and increase through community education
      their awareness of the role of the general practitioner. It involves local GPs
      presenting on health topics to different demographics of indigenous peoples in
      their environments; with their input and endorsement. The BSDGP provides cultural
      awareness training for the presenting GPs and facilitates the education with the
      community groups. The program has been successful in uniting two cultures and two
      different approaches to health.

PMID- 15727355
TI  - The Good Life Club project. Telephone coaching for chronic disease self
      management.

PMID- 15727356
TI  - Managing childhood food allergies and anaphylaxis.
AB  - BACKGROUND: Food allergies in children are becoming more common causing concern
      for parents, child carers, teachers and school principals. OBJECTIVE: This
      article aims to provide practical information on childhood food allergies and
      their ongoing management including assessment, prescription of self or carer
      administered adrenaline, emergency action plans, patient education, school based
      strategies, and family support. DISCUSSION: With most schools, preschools and
      child care centres having at least one child with food allergies, general
      practitioners are increasingly likely to be involved in school liaison and
      education, as well as caring for families with food allergic children.

PMID- 15727357
TI  - Cancer in Australia--an update for GPs.
AB  - BACKGROUND: General practitioners have a critical role to play in cancer control
      in Australia. Their work spans the full spectrum of cancer care--prevention,
      detection, treatment and palliation, and includes psychosocial support of
      patients and carers. The general practitioner practises clinical medicine in a
      very different setting and context from those of the hospital specialist.
      Problems are often undifferentiated, and illness is more common than disease.
      OBJECTIVE: This article provides an update on cancer, covering incidence,
      prevalence, mortality, age distribution, survival, costs, trends and screening.
      DISCUSSION: From a primary care perspective, patients with a new diagnosis of
      cancer are infrequent, but providing ongoing care for patients with an
      established diagnosis of cancer, and their carers, poses substantial issues. The
      average practitioner will encounter about four new patients each year who will be
      diagnosed with a potentially fatal cancer, and have about 16 patients at any one
      time with a diagnosed cancer under their care.

PMID- 15727358
TI  - Multiple superficial basal cell carcinomata--topical imiquimod versus curette and
      cryotherapy.
AB  - BACKGROUND: Superficial basal cell carcinoma can be successfully managed by means
      other than surgical excision. Nonexcisional approaches include topical imiquimod,
      and curette and cryotherapy (C&C). OBJECTIVE: This article discusses the
      management of an insulin dependent diabetic man aged 52 years presenting with 17
      torso basal cell carcinomas (BCCs); mostly superficial BCCs (SBCCs). DISCUSSION:
      Half were treated with topical imiquimod. The remaining lesions were treated with
      curette and cryotherapy. All lesions resolved with proven histologic clearance.
      The patient considered C&C caused him less discomfort and disruption. He
      developed a late secondary infection in some sites treated with imiquimod. At 12
      months there was no evidence of recurrence though new nodular BCCs and SBCCs had
      developed elsewhere on his upper torso. He has elected to have future SBCCs
      managed with C&C. While excisional surgery remains the benchmark management for
      nonmelanoma skin cancer, topical imiquimod and C&C are important options for
      treating SBCCs.

PMID- 15727359
TI  - The NSW & ACT Hereditary Cancer Registers.
AB  - BACKGROUND: The NSW & ACT Hereditary Cancer Registers (HCR) offer registration to
      people from families at risk for hereditary cancer. OBJECTIVE: This article
      describes the Hereditary Cancer Registers and provides information to the
      treating health professional to register patients at risk of hereditary cancer to
      the HCR. DISCUSSION: The HCR collaborates with treating doctors and familial
      cancer clinics to play an important role in the management of people at risk of
      hereditary bowel cancer.

PMID- 15727360
TI  - Quality, innovation, and leadership in general practice--what do they have in
      common?

PMID- 15727362
TI  - Why we need to learn standardisation.

PMID- 15727361
TI  - Divisions of general practice, capacity building and health reform.
AB  - The development of the divisions of general practice network has been one of the
      major health innovations of the past decade. Its establishment was an innovative
      plan to build capacity in general practice to respond to health needs in the
      community and develop good quality health services. The network has a secure
      place in the health system and assists general practitioners to become involved
      at all levels of health policy and decision making. This capacity has facilitated
      multiple health reforms including immunisation and information technology,
      leading to improved health outcomes for the Australian community.

PMID- 15727363
TI  - How to use a case manager--a partnership approach.
AB  - There is great scope for general practitioners and case managers to work
      together. An agreement regarding roles and responsibilities negotiated between
      GPs and service providers assists in the resource efficient provision of care and
      can result in positive outcomes for patients. This article describes how a GP can
      effectively use a case manager in a partnership approach.

PMID- 15727364
TI  - Anaphylaxis--a patient perspective.
AB  - In order to help us better understand our patients' experiences, Australian
      Family Physician is pleased to introduce the first in a series of articles
      written by people who are willing to share their stories. Ella was requested to
      write this article by AFP's Editor in Chief. Ella is now a year 11 student at
      Williamstown High School, Victoria.

PMID- 15727365
TI  - Can children and adolescents consent to their own medical treatment?
AB  - This article examines the legal obligations of general practitioners when
      obtaining consent to medical treatment from patients who are under the age of 18
      years.

PMID- 15727366
TI  - Clinical diagnosis and management of suspicious pigmented skin lesions--a survey
      of GPs.
AB  - BACKGROUND: The ability of general practitioners to make important clinical
      decisions about the diagnosis and management of skin lesions is poorly
      understood. METHODS: A questionnaire on the diagnosis and management of eight
      photographed skin lesions was sent to 150 GPs in southeast Queensland. RESULTS:
      The questionnaire was completed by 114 GPs (response rate 77%). General
      practitioners' provisional diagnoses and management of photographed skin lesions
      were mostly or always correct, and there was general high consistency between
      diagnosis and intended management. Pigmented seborrhoeic keratoses were the most
      difficult lesions for GPs to diagnose correctly. Whether a lesion was different
      to usual moles appears to have the strongest association with clinical diagnosis.
      DISCUSSION: The high ability of GPs as measured in this artificial study is
      encouraging. The strong association between identifying moles that appear
      different to usual and correct clinical diagnoses suggest that unless GPs can
      increase the number of skin lesions they see as part of their typical workload,
      their clinical ability may not increase further.

PMID- 15727367
TI  - Improving the learning needs survey by using four approaches.
AB  - BACKGROUND: Learning needs analyses are often undertaken to plan continuing
      education programs. They usually use questionnaires that have shortcomings
      regarding validity, relevance, breadth and detail. We tested a questionnaire
      using four questioning strategies to approximately 1762 general practitioners.
      METHOD: Our questionnaire listing 104 topics asked open ended questions and
      specific information about desired topics. It was distributed by The Royal
      Australian College of General Practitioners and divisions of general practice in
      South Australia and the Northern Territory. RESULTS: The survey yielded 578
      responses (33%). The different survey strategies highlighted different areas of
      learning need. Overall, the highest ranked topics were dermatology, complementary
      medicine, psychiatry, and business and practice management. Participating
      divisions were generally satisfied with the feedback. DISCUSSION: Despite a poor
      response rate, the survey provided interesting information, and a set of broad
      learning topics.

PMID- 15727368
TI  - The use of therapeutic flags to assist GPs prescribing for older persons.
AB  - BACKGROUND: Prescribing for older persons can present challenges for general
      practitioners. METHODS: Forty-one GPs used a series of statements about
      appropriate drug use (therapeutic flags) to review the medications of 727 older
      patients. RESULTS: Following the review, 14.5% of prescribed medications were
      changed including 6% stopped. Another 7% were associated with other activities
      such as monitoring of therapy as recommended by guidelines. General practitioners
      regarded therapeutic flags as informative and suggested they should be integrated
      with prescribing software. DISCUSSION: Therapeutic flags may assist the provision
      of quality medication to older patients.

PMID- 15727369
TI  - After hours care--a qualitative study of GPs' perceptions of risk of violence and
      effect on service provision.
AB  - BACKGROUND: Workplace violence in general practice has been found to be an
      important problem in the United Kingdom. No research has been undertaken in this
      area in Australian urban practice. METHOD: Four focus groups involved 18 urban
      general practitioners and over 9 hours of taped responses were transcribed. The
      transcripts were coded and subjected to thematic analysis. RESULTS: General
      practitioners expressed a wide range of risks relating to the provision of after
      hours care. This makes them apprehensive about participating in it. Those who had
      experienced violence, or perceived its risk, had limited their participation in
      after hours care; sometimes completely. DISCUSSION: Structures may be needed to
      support provision of after hours general practice services.

PMID- 15727370
TI  - People aged to 18 years per metropolitan and rural GP.

PMID- 15727372
TI  - Diabetes epidemic in Malaysia.

PMID- 15727371
TI  - Does legislation reduce harm to doctors who prescribe for themselves?
AB  - OBJECTIVE: To consider the issue of legislation restricting self prescribing by
      doctors. METHOD: Searches of the medical literature in Medline, Australian
      Medical Index and CINAHL using the terms 'medical', 'legislation' and 'physician
      impairment' from 1966-2003 supplemented by checking citations of review papers.
      RESULTS: We found 144 articles, although no trials of legislation. The remaining
      research was inadequate to answer the question of whether restricting self
      prescribing reduces doctor impairment. However, descriptive studies suggest that
      impairment attributed to self prescribing is most often from self administration,
      which is not altered by legislation to restrict self prescribing. DISCUSSION:
      There are important theoretical adverse consequences of legislation that restrict
      self prescribing. Apparently self evident legislation may be counter productive.
      The need for doctors to have an independent general practitioner is reinforced.

PMID- 15727373
TI  - Isolation of Legionella pneumophila from hospital cooling towers in Johor,
      Malaysia.
AB  - Water-based cooling towers and their water supply at two hospitals in Johor were
      surveyed for the presence Legionella pneumophila. L. pneumophila were grown from
      19 (76%) out of 25 collected water samples. One hospital cooling tower was
      contaminated with L. pneumophila serogroup 1.

PMID- 15727374
TI  - Awareness and knowledge of common eye diseases among the academic staff (non
      medical faculties) of University of Malaya.
AB  - A cross sectional study was conducted to assess the level of awareness and
      knowledge of common eye diseases (cataract, glaucoma, diabetic retinopathy and
      refractive errors) among 473 academic staff (non-medical faculties) of University
      Malaya. The awareness of cataract was in 88.2%, diabetic retinopathy in 83.5%,
      refractive errors in 75.3% and glaucoma in 71.5% of the study population. The
      knowledge about all the above common eye diseases was moderate, except presbyopia
      which was poor. Multivariate analysis revealed that females, older people, and
      those having family history of eye diseases were significantly more aware and
      more knowledgeable about the eye diseases. Health education about eye diseases
      would be beneficial to seek early treatment and prevent visual impairment in the
      society.

PMID- 15727375
TI  - Frozen shoulder syndrome: comparison of oral route corticosteroid and intra
      articular corticosteroid injection.
AB  - Twenty-six patients with frozen shoulder syndrome (Stage 2 and 3) were included
      in this study conducted at Dr. Kariadi General Hospital, Semarang, Indonesia and
      randomly allocated into 2 groups: 40 mg triamcinolone intra-articular injection
      and triamcinolone oral tablets. The result showed that triamcinolone intra
      articular injection group "cured" rate was 5.8 times higher at week one compared
      to the triamcinolone tablet group. Sixty-two percent of the cases with
      triamcinolone intra-articular injection achieved their "cured" condition after
      one week of therapy, compared with only 14% of the triamcinolone tablets group.
      We conclude that, intra-articular corticosteroid injection provide faster
      improvement compared to oral route.

PMID- 15727376
TI  - Audit of diabetes mellitus in general practice.
AB  - An audit on diabetic management was done in seven Perak general practice (GP)
      clinics in December 2001. The results showed inadequacies in nine out of eleven
      criteria assessed. Remedial measures were implemented. A second audit in March
      2003, at the completion of the audit cycle, showed improvements in all the
      criteria used. All clinics established a diabetic register compared to 28.6% in
      the first audit and 57.1% of the clinics set up a reminder mechanism compared to
      0% in the first audit. In the process of care, recording of weight, height, blood
      pressure; feet examination, fundoscopy, blood sugar monitoring and urine for
      albumin improved at the end of the audit cycle. In the only outcome criteria, the
      blood sugar control improved from 21.8% to 31.3%.

PMID- 15727377
TI  - Surgical access to parapharyngeal space tumours--the Manipal experience.
AB  - A few series of parapharyngeal space tumours have been reported earlier but
      recently not many series have been published in English literature. It is rare
      for any medical center, let alone an individual surgeon, to develop sufficient
      experience in evaluating these tumours. We present our experience in the
      treatment of 41 cases of parapharyngeal tumours from January 1992 to December
      2001. FNAC, ultrasound and CT scan of the presenting mass was done in most of the
      patients as the main pre-operative work-up. The strategic location and extension
      of the tumour may occasionally alter the surgical approach for tumour excision.

PMID- 15727378
TI  - A clinical appraisal of patients with psoriasis treated in Seremban General
      Hospital, Malaysia.
AB  - A prospective clinical study of 181 patients with psoriasis seen in Seremban
      General Hospital showed the incidence of psoriasis among dermatology outpatients
      was 2.15%. A significantly higher proportion of male patients were affected, with
      a male to female ratio of 1.7:1. Within the racial groups; 63 were Malays, 37
      Chinese, and 81 Indians. There was a significantly higher proportion of Indians
      affected as compared with the races. The mean age of patients in this study was
      43.7 years old but the mean age of onset of psoriasis in these patients was 33.1
      years old. Thirty-one (17.1%) patients gave a positive family history of
      psoriasis and the mean age of onset of psoriasis was lower (29.3 years old) for
      patients with a positive family history. Plaque psoriasis was the commonest type
      of clinical presentation with the scalp being the commonest site affected.
      Psoriatic arthropathy was seen in 35 (19.3%) patients. Ninety-five (52.5%)
      patients gave a positive history of factors exacerbating their pre-existing
      disease and stress was singled out as the most common exacerbating factor.

PMID- 15727379
TI  - Metered-dose inhaler technique in asthmatic patients--a revisit of the Malaysian
      scene.
AB  - Inefficient metered-dose inhaler (MDI) technique results in poor drug delivery,
      suboptimal disease control a possibility of inhaled medication overuse. The MDI
      technique of 134 government hospital and clinic followed-up adult asthmatic
      patients followed-up in a government hospital and a heath clinic was
      pragmatically assessed based on the 3 obligatory steps of adequate lip seal,
      appropriate hand-breath coordination and sufficient breath holding after
      inhalation. The relationship between technique efficiency and frequency of daily
      short-acting beta2-agonist (SABA) use via the MDI and asthma exacerbations over a
      12-month period was also assessed. Fifty-six patients (42%) had inefficient MDI
      technique. All demographic and asthma-related variables between the 'efficient'
      and 'inefficient' technique groups of patients were comparable except for
      significantly longer mean years of MDI use in the 'efficient' technique group
      [mean (SD): 10 (7) vs. 7 (5); p=0.003]. There were no significant differences
      between the two groups in relation to frequency of daily SABA use or asthma
      exacerbations over the past 12 months. Despite having been available in Malaysia
      for a considerable period of time, the MDI device is still poorly handled by a
      large proportion of adult asthmatic patients. Changing to other more user
      friendly devices or use of spacer devices to facilitate delivery should be
      considered for these patients.

PMID- 15727380
TI  - Acute disseminated encephalomyelitis: a report of six cases.
AB  - Six children with Acute Disseminated Encephalomyelitis (ADEM) were seen at the
      Penang Hospital over a two year period (July 1999-June 2001). Diagnosis was based
      upon typical clinical features and characteristic findings on neuroimaging.
      Cerebrospinal fluid examination and other investigations were done, where
      appropriate, to rule out other causes of central nervous system disease. Three
      children had a prodromal illness. The most common presenting symptoms were fever,
      seizures, ataxia, focal neurological deficits and labile mood. Two children
      presented with status epilepticus. All children had an abnormal neurological
      examination. Brain magnetic resonance imaging revealed hyperintense signals on T2
      weighted and FLAIR sequences in the subcortical and deep white matter regions of
      the frontal, parietal, and temporal lobes, as well as in the thalami, cerebellum
      and brainstem. One child had multiphasic disseminated encephalomyelitis (three
      episodes). The child with multiphasic disease had only one treated episode, and
      has suffered mild disability. Three children were treated with either
      methylprednisolone or immunoglobulins, and remain well. One child received both
      treatments but expired as a result of severe gastrointestinal bleeding from the
      use of methylprednisolone. The child who was not treated has severe disability.

PMID- 15727381
TI  - Comparative bioavailability study of a generic sustained release diclofenac
      sodium tablet.
AB  - The bioavailability of a generic diclofenac sodium sustained release tablet
      preparation (Zolterol, SR) was compared with the innovator product, Voltaren, SR.
      Twelve healthy adult male volunteers participated in the study, which was
      conducted according to a randomized, two-way crossover design with a wash out
      period of one week. The bioavailability of diclofenac was compared using the
      parameters area under the plasma concentration-time curve (AUC(0-infinity)), peak
      plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax).
      No statistically significant difference was observed for both logarithmically
      transformed AUC(0-infinity), Cmax values and Tmax value of the two preparations.

PMID- 15727382
TI  - Familial aggregation and determinants of post challenge blood glucose in four
      ethnic populations.
AB  - We determine the familial aggregation and determinants of post challenge blood
      glucose (BG) in four ethnic populations. A national health survey was conducted
      in Malaysia in 1996. 18,372 subjects aged 30 years or older had post challenge BG
      measurements and another 846 subjects were pre-diagnosed to have diabetes on drug
      treatment. We imputed the BG of diagnosed diabetics by randomly selecting a value
      from the BG distribution of undiagnosed diabetics. Covariates of interest include
      ethnicity, gender, age, urban-rural residence, body mass index (BMI), physical
      activity, education, and household income. Ethnic and gender differences in mean
      BG persisted after adjustment for other covariates. Age and BMI were the only two
      factors with strong, positive and consistent effects on mean BG in all ethnic-sex
      groups. Family resemblance for BG as measured by intraclass correlation was small
      and homogenous across all ethnic groups and did not differ from resemblance in BG
      between spouses. In conclusion, BMI was the only consistent modifiable predictor
      of BG in all ethnic-sex groups. Environmental factors are probably more important
      than genetic factors as determinant of BG in the four ethnic populations studied.

PMID- 15727383
TI  - Antibodies in systemic lupus antineutrophil cytoplasmic erythematosus:
      prevalence, disease activity correlations and organ system associations.
AB  - Systemic Lupus Erythematosus (SLE) is a disease with multiorgan involvement and
      multiple autoantibody production including antineutrophil cytoplasmic antibodies
      (ANCA). Despite its reported prevalence in more than one third of SLE patients,
      the role of ANCA in the pathogenesis or otherwise in SLE remains unresolved. 131
      SLE patients had been previously studied for various serologic parameters of
      disease activity. Their cumulative organ involvement in the course of their
      disease had also been determined and the Lupus Activity Index (LAI) calculated.
      Their stored sera were then screened for the presence of ANCA by two methods viz
      Indirect immunofluorescence (IIF) and also enzyme-linked immunosorbent assay
      (ELISA). ANCA was present in 24.8% of these SLE patients. The atypical ANCA
      pattern was predominant and accounted for an overall of 20.6%. Anti-MPO and anti
      PR3 were detected in 1.5% of patients respectively. No association was found
      between ANCA positivity and disease activity. There was also no association of
      ANCA with specific organ involvement. Despite the high prevalence of ANCA
      especially the atypical variant in SLE, they probably represent only one of the
      wide repertoire of autoantibodies found in this disease. Routine testing for ANCA
      in lupus patients is therefore not recommended.

PMID- 15727384
TI  - Trabeculectomy--a review and 2 year follow up.
AB  - This study reviewed the trabeculectomies (TEs) carried out in University Malaya
      Medical Center between 1994 to 1998. One hundred and nine of 132 eyes operated
      were in the primary glaucoma group of which 63 (47.7%) were of the open angle
      type and 46 (34.8%) were of the angle closure type. Twenty-three eyes belong to
      the secondary glaucoma group. Sixty-five eyes had plain or non-augmented
      trabeculectomy (TE) while 20 were augmented with mitomycin C (MMC) and 11 with 5
      flourouracil (5FU). In 31 eyes the plain TEs were combined with extracapsular
      cataract extraction (ECCE) and 4 with phacoemusification. One case had combined
      ECCE and augmented trabeculectomy with mitomycin-C. The patients were followed up
      at 1 month, 6 months, 1 year and 2 years. Ninety-four of 132 (71.2%) eyes had
      successful surgery with intraocular pressure (IOP) of less than 21 mmHg
      (tonometric success) at the end of 2 years. Four of these patients needed topical
      medication for the IOP control. More failures were seen in patients with cystic
      blebs than those with diffuse blebs. Complications include hypotony, shallow
      anterior chamber, cataracts and hyphaema. The majority of cases (53%) had no
      complications.

PMID- 15727385
TI  - Coping styles of mothers with disabled children at rural community rehabilitation
      centres in Muar, Malaysia.
AB  - Chronic disability in children imposes great strains on a family. The
      responsibility of mothering disabled children may be detrimental to the well
      being of mothers. This study aims to assess the different types of coping styles
      of mothers with disabled children and its influencing factors. It is a cross
      sectional study using Coping Inventory Stressful Situation (CISS) scale to
      determine the mothers' coping styles. A sample of 81 mothers with disabled
      children attending two rural Community Rehabilitation Centres, were included in
      the study. Overall, the mothers were using a mixture of coping strategies.
      However, they scored more in the task-oriented (mean T score = 52.88) and emotion
      oriented (mean T score = 50.52) coping styles, while the other subscales of
      coping styles, namely avoidance, distraction and social diversion were below
      average (mean T score < 50). Divorced mothers (p=0.04) and those with low
      educational level (p=0.00) were more inclined to use emotion-oriented coping
      strategies while mothers with younger children (< 5 years old) used more
      avoidance coping strategies (p=0.01). There were no significant difference of
      coping styles in association with the mothers' age, ethnicity, duration of
      marriage, number of siblings, child's birth order or gender. By understanding the
      mothers' coping styles, health care workers would be able to educate the mothers
      with effective coping strategies and consequently reduce their psychological
      distress.

PMID- 15727386
TI  - Effect of pentoxifylline on tumor necrosis factor-alpha and interleukin-6 levels
      in neonatal sepsis.
AB  - Several pharmacological agents have been found to alter systemic concentrations
      and/or the activity of different cytokines via a variety of mechanisms, including
      changes in biosynthesis, secretion, and/or stability. Pentoxifylline (PTX), which
      is a methylxanthine derivative for example, has multiple effects on the immune
      system, but inhibition of pro-inflammatory cytokine release predominates. In this
      study we aimed to evaluate the influence of PTX on plasma levels of tumor
      necrosis factor (TNF) alpha and interleukin (IL)-6 in newborn infants with
      sepsis. The study included 20 infants with neonatal sepsis. In all subjects blood
      samples for serum C-reactive protein, TNF alpha and IL-6 determinations were
      received before giving PTX and at the 12th and 24th hours following PTX. In
      addition, white blood cell was counted before giving PTX and on the 3rd and 7th
      day following PTX. The infants were randomly divided into two groups. Firstly,
      PTX was used in infants who were successively admitted to the clinic and the
      subsequent infants were accepted as a control group. Of 20 infants, 13 infants
      received PTX and seven infants did not. We did not find any difference in the
      leukocyte count, serum C-reactive protein level, TNF alpha and IL-6 levels
      between the two groups of patients (P>0.05). While three infants died in the
      group of receiving PTX, death was not recorded in the group of non-receiving PTX
      (P>0.05). Our findings showed that PTX treatment did not affect leukocyte counts,
      serum CRP levels, TNF alpha and IL-6 levels and death ratio in newborn infants
      with sepsis. The last result may be due to the fact that the number of patients
      in the study was very small. We think that more extensive and controlled studies
      should be performed about this subject.

PMID- 15727387
TI  - Effectiveness of home versus hospital phototherapy for term infants with
      uncomplicated hyperbilirubinemia: a pilot study in Pahang, Malaysia.
AB  - A comparative pilot study was conducted to determine the difference in the
      reduction of total serum bilirubin in a group of infants who had phototherapy at
      home compared to an in-patient group on hospital phototherapy. Eighteen infants
      with unconjugated hyperbilirubinaemia who fitted the selection criteria were put
      under the mobile home unit (Bluelite Portable Light) placed in the home. A
      control group of 18 infants with the same matching characteristics had intense
      phototherapy in the hospital using a unit with top and bottom light sources. The
      infants were matched for race, starting total serum bilirubin level, birth weight
      (up to 250 grams) and age of baby at initiation of phototherapy (up to one-day
      difference). It was observed that the mean daily decrease in serum bilirubin
      concentration was significantly more in the home group as compared to the
      hospital group (t=2.95, df=17, P<0.05). The mean duration of treatment was
      significantly less for the home group as compared to the hospital group (t=2.84,
      df=17, P<0.05). None of the infants who had home phototherapy were re
      hospitalized. Phototherapy related complications were mild and comparable in both
      groups. The result suggests that home phototherapy is safe and effective in
      bringing down the concentration of serum bilirubin for term babies with
      uncomplicated hyperbilirubinaemia.

PMID- 15727388
TI  - Prebiopsy localisation of impalpable breast lesions.
AB  - Prebiopsy localization of impalpable breast lesions (IBL) assures removal of
      suspicious mammographically detected lesions. Specimen radiograph of the excised
      specimen is mandatory to confirm complete excision. The aim of this study was to
      audit our series of percutaneous hookwire localization and to determine the
      positive biopsy rate of the mammographically detected impalpable breast lesion in
      our center. Thirty-eight patients with suspicious IBL underwent excision biopsy
      under mammographic localization in our unit from late February 1998 to May 2003.
      The excised specimen is immobilized and compressed within the Transpec device.
      This device incorporates a reference grid visible in the specimen radiograph.
      Hence, the target lesion marked in the reference grid of the specimen radiograph
      will allow precise examination and exact localization of the suspicious lesion by
      the pathologist. The positive biopsy rate for malignant lesion was 26.3%, the
      majority fall in the range of 40-59 age group. Thirty-two (84.2%) of the patients
      had clustered micro-calcifications, 4 (10.5%) had impalpable mass lesions and in
      2 (5.3%) spiculated lesions were seen on the preoperative mammogram. Mammographic
      feature of clustered micro-calcification accounts for all the malignant lesions
      in our series. Utilization of Transpec device has shown to be practical, reliable
      and cost effective in the management of IBL. Nonetheless, it should be emphasized
      that optimal specimen radiography and pathological correlation requires close
      cooperation between radiologist, surgeon and pathologist.

PMID- 15727389
TI  - Lipoprotein (A) levels in type 2 diabetic patients with diabetic retinopathy.
AB  - To examine a possible association between lipoprotein(a) [Lp(a)] levels and
      diabetic retinopathy in patients with type 2 diabetes mellitus. 100 type 2
      diabetic patients were assessed with the following parameters: age, body mass
      index, duration of diabetes, blood pressure, fasting plasma glucose, total
      cholesterol, HDL-cholesterol, triglycerides, blood urea nitrogen, creatinine,
      Lp(a), and albumin excretion rate (AER). Retinopathy was classified as normal
      retina (NR), non-proliferative diabetic retinopathy (NPDR), and proliferative
      diabetic retinopathy (PDR) by an ophthalmologist. The PDR group had higher
      cholesterol (t=-2.24, p<0.05) and creatinine (z=-2.547, p<0.05) levels than the
      NPDR group. The PDR group had a higher value of AER (z=-2.439, p<0.01) than the
      NR group. The possibility of developing diabetic retinopathy after 10 years of
      diabetes was found to be 6.5 fold high (OR; 6.57, 95% CI 1.74-24.79; p<0.05). The
      Lp(a) levels were similar in the patients with retinopathy and those without
      retinopathy. In the study, there was no evidence for a relationship between the
      serum Lp(a) levels and diabetic retinopathy in type 2 diabetic patients.

PMID- 15727390
TI  - Glycaemic control of diabetic patients in an urban primary health care setting in
      Sarawak: the Tanah Puteh Health Centre experience.
AB  - Achieving glycaemic goals in diabetics has always been a problem, especially in a
      developing country with inadequate facilities such as in Sarawak in Malaysia.
      There are no reported studies on the control of diabetes mellitus in a diabetic
      clinic in the primary health care setting in Sarawak. This paper describes the
      profile of 1031 patients treated in Klinik Kesihatan Tanah Puteh Health Centre.
      The mean age was 59 years, the mean BMI 27 kg/m2. There was a female
      preponderance and mainly type-2 diabetes. Mean HbA1c was 7.4%. Glycaemic control
      was optimal in 28% (HbA1c <6.5%), fair in 34% (HbA1c 6.5-7.5%) and poor in 38%
      (HbA1c >7.5%). Reasonable glycaemic control can be achieved in the primary health
      care setting in Sarawak.

PMID- 15727391
TI  - Methyl methacrylate cranioplasty.
AB  - We conducted a prospective study in order to audit our experience of repairing
      cranial defects using Methyl methacrylate. This included a total of 49 patients
      undergoing cranioplasty using methyl methacrylate, of which 45 were males and 4
      females. The age of patients at the time of surgery ranged from 16 to 40 years
      old, with an average of 24 years. Malays were the majority (67%), followed by
      Chinese (23%) and Indian (10%). Cranial defects were mainly caused by motor
      vehicle accident (94%), while gunshot wounds, industrial accidents and tumours,
      each contribute 2%. Bone flaps were commonly removed during previous surgery
      related to traumatic subdural haemorrhage (33%), contusion (21%) and
      intracerebral haemorrhage (14%). The size of cranial defects ranged from 28 cm2
      to 440 cm2, with an average of 201 cm2. Most had right sided (55%) and lateral
      defects [temporoparietal (52%) followed by temporal (16%), frontal (16%),
      frontotemporal (14%) and occipital (2%)]. Duration of surgery ranged from 70 to
      275 minutes, with an average of 135 minutes. Nine of 12 patients (75%) with
      neurological disability had some improvement while 85% of symptomatic patients
      had symptoms improvement after cranioplasty. The infection rate in this series
      was 4%.

PMID- 15727393
TI  - Intraabdominal haemangiopericytoma associated with uncontrolled diabetes
      mellitus.
AB  - Haemangiopericytoma (HPC) is a rare tumour with a predilection for the central
      nervous system. Though previously thought to originate from the meninges and
      ventricular walls, HPC's are currently accepted as distinct mesenchymal neoplasms
      unrelated to meningiomas. Haemangiopericytomas have been previously reported to
      be associated with the production of insulin like growth factor II (IGF-II) and
      hypoglycaemia. A case of a 61-year-old poorly controlled diabetic lady with a
      rare presentation of an abdominal haemangiopericytoma is discussed. A
      laparoscopic assisted resection of the massive lobulated tumour arising from the
      parietal peritoneum with dense attachment to the diaphragm and the liver was
      performed with an uncomplicated postoperative recovery. Control of the patient's
      diabetes improved dramatically following surgery and the rare association of
      hyperglycaemia and HPC, which has not been previously described, is elaborated
      upon in this report.

PMID- 15727392
TI  - Giant serpentine middle cerebral artery aneurysm.
AB  - A rare case of partially thrombosed giant serpentine right middle cerebral artery
      aneurysm presented. A 26 year old man initially presented with headache and 3
      months later developed neurological deficit. Various stages of clot with patent
      residual lumen seen on neuroimaging, led to the diagnosis. Catheter angiography
      is the investigation of choice for evaluating the location, flow dynamics and
      extent of the serpentine aneurysm. The patient had embolisation done for the
      giant serpentine aneurysm.

PMID- 15727394
TI  - Hashimoto's thyroiditis: a rare cause for rhinosinusitis.
AB  - Rhinosinusitis is a common disorder with various etiological factors. In our
      clinical practice allergy seems to be a predominant cause followed by other less
      common causes like infection, drugs and aspirin hypersensitivity. We present a
      case of chronic rhinosinusitis secondary to hypothyroidism. Although hormonal
      causes like hypothyroidism have been proven to cause nasal congestion and
      rhinosinusitis, this is the first reported case of chronic rhinosinusitis in
      Hashimoto's thyroiditis in our center. This is a diagnosis of exclusion for
      chronic rhinosinusitis not responding to optimal medical therapy.

PMID- 15727395
TI  - Response of undergraduate medical students to SARS.

PMID- 15727396
TI  - Oral health care in the elderly population in Malaysia--a review.
AB  - One of the undeniable facts about living is that everyday we are getting older.
      By 2050, it is projected that one out of every five Malaysians will be 60 or
      older. The economic challenge of this demographic change will affect development
      and the financial implications of sustaining well being of this group are
      formidable and complex. This population group has extensive oral disease, medical
      problems that complicate their oral care, and unique dental treatment challenges.
      The authors discuss the problem of oral healthcare among the aged, its
      impediments and propose some approaches for improvement to better serve the needs
      of this group of vulnerable members of our nation.

PMID- 15727397
TI  - Group A beta-hemolytic streptococcal pharyngitis in children.
AB  - Group A beta-hemolytic streptococcus (GABHS) is the most common bacterial cause
      of acute pharyngitis in children. Because clinical findings can be nonspecific,
      even experienced physicians cannot reliably diagnose GABHS pharyngitis solely on
      the basis of clinical presentation. Suspected cases should be confirmed by a
      throat culture or a rapid antigen detection test before antibiotic therapy is
      initiated. Microbiologic testing is generally not necessary in patients with
      pharyngitis whose clinical and epidemiologic findings are not suggestive of
      GABHS. Clinical score systems have been developed to help physicians decide which
      patients should undergo diagnostic testing and to reduce the unnecessary use of
      antibiotics. Antibiotic therapy should be initiated as soon as the diagnosis is
      confirmed. Penicillin V remains the drug of choice. Alternative therapy, e.g.,
      with cephalosporin or macrolide, is often sought because of penicillin allergy,
      noncompliance, and treatment failure.

PMID- 15727398
TI  - Predicting the risk for gastrointestinal toxicity in patients taking NSAIDs: the
      Gastrointestinal Toxicity Survey.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used
      drugs in the world, but their use is often associated with adverse
      gastrointestinal (GI) events that may be life threatening in some patients.
      Development of simple questionnaires for predicting GI events in individuals
      taking NSAIDs may help to prevent use of these drugs in high-risk patients. The
      present study was undertaken to test a new questionnaire designed to identify
      patients at high risk for NSAID-associated GI events--the Gastrointestinal
      Toxicity Survey (NSAID Induced) (GITS [NI]). In this study, results for GITS (NI)
      were compared with those for an established questionnaire, the Stanford
      Calculator of Risk for Events (SCORE), in a small cohort of 400 patients.
      Feasible generalized least squares (FGLS) and multinomial logistic (MNL)
      regression were used to perform the comparison. The overall correlation between
      results for GITS (NI) responses and the total score for the SCORE questionnaire
      was 0.962 (P < .0001). The agreement between the 2 instruments with respect to
      their ability to predict the same risk for NSAID-induced GI events was similar
      for both FGLS and MNL. For 4 levels of risk, the agreement was approximately 80%
      between the 2 instruments. For 3 levels of risk, the agreement was approximately
      90%. This study showed that results obtained with GITS (NI) are highly correlated
      with those from SCORE and that GITS (NI) may provide physicians with information
      that will help them avoid administering NSAIDs to patients who are at high risk
      for adverse GI reactions.

PMID- 15727399
TI  - Endocrine effects of organophosphate antidotal therapy.
AB  - To determine the endocrine effects of the treatment of organophosphate poisoning,
      this prospective study was conducted in a university-based emergency department
      among patients with a history and clinical findings compatible with those of
      organophosphate poisoning. Thyrotrophin (TSH), free triiodothyronine (FT3), free
      thyroxine (FT4), follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      prolactin (PRL), progesterone (PRG), adrenocorticotropic hormone (ACTH),
      cortisol, and testosterone (TST) levels were analyzed before and after treatment
      with atropine and pralidoxime. The Wilcoxon's sign rank sum (nonparametric) test
      was used to compare dependent variables before and after treatment. A total of 44
      patients (19 male; mean age: 28.5 +/- 12.6 y) were enrolled in the study.
      Patients were hospitalized for 5.4 +/- 1.3 days. Posttreatment ACTH, cortisol,
      PRL, FT3, FSH, and PRG levels were significantly lower than pretreatment levels
      (P < .05). The decrease in TSH, LH, and TST levels did not reach statistical
      significance, while FT4 levels increased following the treatment (P < .05). Six
      patients were diagnosed on admission with sick euthyroid syndrome, and 11
      patients who were euthyroid on admission developed sick euthyroid syndrome
      following treatment. ACTH, cortisol, PRL, FT3, FT4, FSH, and PRG levels are
      affected by acute organophosphate poisoning. The change in hormone levels may
      result from the effects of neurotransmitters, from the direct effect of the toxic
      agent, or from stress associated with events leading to the poisoning incident.

PMID- 15727400
TI  - Comparison of meperidine plus midazolam and fentanyl plus midazolam in procedural
      sedation: a double-blind, randomized controlled trial.
AB  - This double-blind, randomized, prospective study was conducted to compare the
      analgesic and sedative efficacy of fentanyl and meperidine in orthopedic closed
      reduction of fractures and dislocations undertaken in the emergency department.
      Seventy consecutive adult patients with fractures or dislocations suitable for
      reduction were randomized to receive fentanyl (1 mcg/kg; n = 36) or meperidine
      (0.5 mg/kg; n = 34) in combination with midazolam (0.02 mg/kg). Vital signs and
      alertness scale scores of the patients were monitored. The Visual Analog Scale
      (VAS) was used to determine the degree of pain. There was no statistically
      significant difference between the VAS mean scores of the fentanyl and meperidine
      groups (t test, P = .772). The need for additional analgesic drugs was
      significantly more frequent in patients receiving meperidine (P = .018). No
      adverse events, such as hypotension or respiratory depression, were noted.
      Euphoria occurred in one patient in the fentanyl group. Although dose
      requirements differ, fentanyl and meperidine provide effective and reliable
      analgesia in closed reduction of fractures and dislocations.

PMID- 15727401
TI  - Surgical outcome following treatment of isolated subaortic obstruction.
AB  - Surgical and nonsurgical patients with isolated subaortic stenosis (SAS) were
      compared to determine the important factors contributing to the timing of
      surgical intervention. This study reviews 49 consecutive patients (27 surgical
      and 22 nonsurgical) aged 1.8 to 15.9 years with isolated SAS. The preoperative
      peak left ventricular outflow tract (LVOT) gradient in surgical patients was
      significantly higher than the gradient in nonsurgical patients (59.0 +/- 30.4 vs
      22.77 +/- 13.9 mm Hg, P = .0001). The progression in LVOT gradient analyzed by
      echo Doppler was significantly higher in the surgical group compared with the
      nonsurgical group (10.48 +/- 9.7 vs 1.56 +/- 6.5 mm Hg/y, P = .007). Repeat
      surgical intervention was required in 22% of patients in the surgical group for
      recurrence of SAS, and 4% needed a third surgery. The progression in the severity
      of aortic regurgitation (AR) was not significantly different in the surgical and
      nonsurgical groups. There was a significant association between the development
      of AR and patients undergoing surgery (P = .045). AR may not be a reliable
      indication for early operative intervention in isolated SAS as there was no
      significant difference in its progression with surgical and nonsurgical patients.
      Asymptomatic patients with isolated SAS may warrant surgical intervention on the
      basis of progression of LVOT gradient, rather than the development or progression
      of AR.

PMID- 15727402
TI  - Paramedics and triage: effect of one training session on triage in the emergency
      department.
AB  - This 3-stage intervention study enrolled all adult patients referred to a
      university-based emergency department (ED) during randomly assigned 1-week
      preeducation or posteducation periods. Triage decisions recorded by ED paramedics
      (n = 8) both before and after an educational training session were compared to
      decisions made by emergency physicians (EPs). Triage decisions of paramedics and
      EPs in the preeducation phase showed poor consistency (K = 0.317, K = 0.388).
      Triage decisions in the posteducation phase increased slightly but were still
      found to be low. On the other hand, consistency between the triage assessments
      recorded by paramedics and EPs of the general appearance of patients increased
      from low in the preeducation phase to moderate in the posteducation phase (K =
      0.327, K = 0.500, respectively). The training session was associated with a
      slight increase in the consistency of triage decisions recorded by paramedics and
      EPs.

PMID- 15727403
TI  - Avascular necrosis and nonunion after osteosynthesis of femoral neck fractures:
      effect of fracture displacement and time to surgery.
AB  - This study assessed the effect of fracture displacement and elapsed time before
      surgery on the development of avascular necrosis and nonunion after internal
      fixation of femoral neck fractures. Twenty-eight patients with 30 femoral neck
      fractures who underwent internal fixation and completed a minimum of 2 years'
      follow-up were retrospectively analyzed. The rates of avascular necrosis and
      nonunion were 12.5% and 25%, respectively, among patients who underwent surgery
      before 12 hours had elapsed and 14% and 27% among those who underwent surgery
      after that time. The rates of avascular necrosis and nonunion associated with
      fracture displacement were 6% and 18%, respectively, among patients with
      undisplaced (Garden stages 1 and 2) fractures and 23% and 38% among those with
      displaced (Garden stages 3 and 4) fractures. Nonunion and avascular necrosis led
      to the necessity for additional surgery in 11 of 30 (36%) hips. Internal fixation
      of femoral neck fractures is associated with a high initial complication rate,
      but if successful, the procedure ensures an excellent long-term outcome. Internal
      fixation should be considered the treatment of choice in young patients with
      nondisplaced fractures.

PMID- 15727404
TI  - Older adolescents' positive attitudes toward younger adolescents as sexual
      partners.
AB  - The prevalence of older adolescents' positive attitudes toward younger sexual
      partners was investigated through three measures of self-reported hypothetical
      likelihood of having sex with preadolescents and younger adolescents (LSA), using
      a school-based cluster sample of 710 Norwegian 18- to 19-year-olds attending
      nonvocational high schools in Oslo. Some likelihood of having sex with a
      preadolescent (less than 12 years of age) was reported by 5.9% of the males. The
      19.1% of the males who indicated some likelihood of having sex with a 13- to 14
      year old, compared to those who did not, reported more high-frequency drinking,
      more alcohol-related problems, earlier sexual initiation, more conduct problems,
      and poorer psychosocial adjustment. This subgroup also reported more high
      frequency use of pornography, having more friends with an interest in child
      pornography and violent pornography, and greater use of coercion to obtain sexual
      favors.

PMID- 15727405
TI  - Psychosocial correlates of substance use behaviors among African American youth.
AB  - Cross-sectional data were collected on substance use behaviors and potential
      correlates in 1,494 African American students enrolled in grades 5-12 in eight
      schools in a central Alabama school district. Using a risk and asset framework,
      self-reported recent alcohol, cigarette, and marijuana use were analyzed by
      identifying and measuring levels of influence, including individual, family, and
      school. For alcohol and marijuana use, recurrent risk factors were age, being hit
      by a parent, affiliation with gangs, and a tolerant attitude of peers toward drug
      use. For cigarette use, risk factors were peer-oriented: associations with gangs
      or cohorts holding lenient attitudes about substance use. For all substances,
      salient asset factors were academic achievement and parental monitoring. Findings
      suggest that efforts to reduce substance use behaviors should be directed at
      adolescents in terms of academic achievement and grade level as well as their
      social environments. For the latter, peer/family risks and family/school assets
      should be the foci for programs to minimize the short- and long-term consequences
      of these behaviors. Hence, the emphasis should be placed on modeling attitudes,
      preventing gang and family violence, encouraging parental supervision, and
      building positive teacher-student interactions.

PMID- 15727406
TI  - Black, Hispanic, and White American mothers of adolescents: construction of a
      national standard.
AB  - Black, Hispanic, and White American mothers (n = 739) and adolescents (n = 806)
      completed the Parent Success Indicator to rate maternal performance on subscales
      of Communication, Use of Time, Teaching, Frustration, Satisfaction, and
      Information Needs. A weighted method corresponding to ethnic proportions in the
      American population was applied to construct a national standard for comparative
      reference. In general, both generations perceived mother performance as
      favorable. Teaching received the highest rating followed by Satisfaction levels.
      Mothers felt that Information Needs were their greatest limitation while
      adolescents reported that their mothers were prone to frustration. The amount of
      time mothers and adolescents spent together was the most significant independent
      variable influencing parent performance. Other variables such as income and
      marital status had limited impact.

PMID- 15727407
TI  - Acceptance of and engagement in risky driving behaviors by teenagers.
AB  - Data gathered from 1,430 teenage student drivers and 880 teenage traffic
      violators were used to examine the levels of exposure to risky driving behaviors
      and perceptions concerning the level of danger of such behaviors. For student
      drivers, 55% reported exposure to risky driving by being in a car with a driver
      engaging in such activities as drunk driving, drag racing, and reckless driving.
      For the traffic violators, 43% had been engaged in one or more of the risky
      driving behaviors. Teenagers who had been exposed to risky driving practices were
      more accepting of risky driving behaviors.

PMID- 15727408
TI  - Adolescent loneliness assessment.
AB  - The aim of the present work was to develop a loneliness scale for adolescents in
      order to assess their perceptions of the quality of their relationships with
      parents and peers. The scale was administered to 1,233 Argentine secondary school
      students, aged 13-16 years. Factor analyses (principal axes, oblimin solution)
      were conducted. Four factors were obtained, which accounted for 43.13% of the
      variance: Peer Rejection, Family Deficits and Parent Rejection, Personal
      Inadequacy, and Significant Separation. The internal consistency assessed through
      Cronbach's alpha was satisfactory. We believe that this proposal, which aims at
      evaluating the different processes that cause and are caused by a feeling of
      loneliness, allows for an integral approach to the issue.

PMID- 15727409
TI  - Paternal absence and international migration: stressors and compensators
      associated with the mental health of Mexican teenagers of rural origin.
AB  - Mexico-U.S. migration creates situations that may cause psychological distress.
      The purpose of this research project was to study the impact of father's physical
      absence due to international migration (FPAIM) on adolescent offspring of rural
      immigrants from Zacatecas, Mexico. Stressors and compensators were studied from
      the adolescent's perspective and were analyzed using a stress-mediator
      consequences theoretical framework. Qualitative (n = 24) and quantitative (n =
      310) methodologies were used with a nonrandom sample of adolescents. Results show
      that the FPAIM is an ambivalent experience for adolescents that has positive and
      negative elements. Though migrants' children seem to be more vulnerable to
      psychosocial stress than are the offspring of nonmigrants, gender, not father's
      absence, appears to be the most important risk factor for psychological distress.

PMID- 15727410
TI  - Taiwanese adolescents' perceptions and attitudes regarding the internet:
      exploring gender differences.
AB  - The purpose of this study was to explore adolescents' perceptions and attitudes
      regarding the Internet, by gender. Data were collected from 636 high school
      students in Taiwan. It was found that male adolescents perceived the Internet
      more as a "toy," while female adolescents perceived the Internet more as a
      "technology," "tool" or "tour." Results indicated that females held more
      pragmatic views of the Internet, whereas males believed they could obtain more
      enjoyment from the Internet. In addition, males expressed significantly more
      positive attitudes than did females on two aspects of the Internet: usefulness
      and perceived control. However, no significant gender differences were found in
      terms of the affection and behavior aspects of using the Internet. More
      importantly, females tended to show higher Internet self-efficacy than did males.
      It is suggested that gender differences regarding the Internet might be narrowing
      because female adolescents are acquiring more experience with it.

PMID- 15727411
TI  - Experiences of being homeless or at risk of being homeless among Canadian youths.
AB  - A qualitative study was undertaken with four groups--immigrants, youths,
      Aboriginal people, and landlords--in order to explore, compare, and contrast
      diversity issues among the homeless population and those at risk of homelessness
      in a larger Canadian city (Calgary, Alberta) with a smaller city (Lethbridge,
      Alberta), to better understand their and to needs make recommendations for
      improvement in service delivery and policy formation. This paper focuses on the
      findings from our sample of youths who shared information on a range of factors
      that contributed to their being homeless or at risk of being homeless. The youths
      in this study also shared their positive as well as negative experiences with
      educators, peers, family members, and social service providers. Canada's homeless
      include growing numbers of young people, families, women, and members of various
      ethnic communities, including Aboriginal people and immigrants. Today it is no
      longer possible to articulate a single silhouette of the homeless, but rather a
      diversity of profiles is needed. It was in the light of this reality that a
      study, "Diversity Among the Homeless and Those At Risk," was carried out. It was
      undertaken with four groups--immigrants, youths, Aboriginal people, and
      landlords.

PMID- 15727412
TI  - Anger and aggression among Filipino students.
AB  - This paper describes the extent of anger and aggression in a sample of secondary
      school students in the southern Philippines. A total of 650 students in both
      public and private schools completed a self-report survey of levels of anger and
      aggression, and homeroom teachers rated them on aggression. Results indicated
      that their overall levels of aggression and anger were average. Students in
      private schools had higher overall aggression and anger compared to students in
      public schools. Teachers rated males as having a higher level of aggression
      compared to females. Self-reported anger and aggression were significantly higher
      among older students, but teachers rated them as being less aggressive. The
      implications of these findings for intervention and future research are
      discussed.

PMID- 15727413
TI  - Multicultural education: Israeli and German adolescents' knowledge and views
      regarding the Holocaust.
AB  - This study probes a unique case of multicultural education of Israeli and German
      students regarding the Holocaust. Their knowledge level of German history leading
      to the rise of Hitler and the Nazi party to power, knowledge about the Holocaust,
      the relation between their knowledge of attitudes toward the "other"
      (German/Israeli) group, and their reaction to a racist-dictatorial regime are
      explored. The findings were that German adolescents (high school students)
      knowledge regarding the events leading to the rise of the Nazi party was greater
      than that of the Israeli adolescents. However, the knowledge of Israelis was
      greater regarding the Holocaust. A positive correlation was found between the
      knowledge levels and their attitudes toward the other groups (German/Israeli) and
      toward resistance to the possible rise of a dictatorial regime. The findings
      point to the fact that multicultural education, which combines attitudinal,
      cognitive, and instrumental goals, can succeed in promoting nonracist views.

PMID- 15727414
TI  - Perceptions of present, ideal, and future lives among Chinese adolescents
      experiencing economic disadvantage.
AB  - Perceptions of present, ideal, and future lives among 12 Chinese adolescents
      experiencing economic disadvantage were examined via qualitative interviews.
      Results showed that most of the adolescents evaluated their present lives
      positively. In general, they also had positive perceptions of their future lives,
      although there also were some negative feelings. Although money did not play an
      important role in their perceptions of present lives, future lives, life goals,
      and ideal careers, economic sufficiency emerged as a major theme from the
      perspective of their ideal lives. While adolescents with better psychosocial
      adjustment appeared to evaluate their present lives more positively than did
      adolescents with relatively poorer psychosocial adjustment, no differences were
      found between the two groups in terms of their views on ideal and future lives.

PMID- 15727415
TI  - Coping attitudes, sources, and practices among Black and Latino college students.
AB  - We investigated 130 Black and Latino college students regarding their concerns,
      attitudes toward professional counseling, sources of support, and coping
      activities. We found that the Black and Latino cultural emphasis on
      interdependence influenced attitudes toward using professional resources such as
      a counselor. We also found a significant two-way interaction between gender and
      race for attitudes toward professional counseling: Black males had less favorable
      attitudes in comparison to Black females, while Latino males had more favorable
      attitudes than did Latino females. Both Black and Latino college students had
      favorable attitudes toward informal support networks. Differences between Black
      and Latino college students were found for reported concerns and coping sources.
      Implications for counseling theory, practice, and research are discussed.

PMID- 15727416
TI  - Adolescents' psychological health and experiences with unwanted sexual behavior
      at school.
AB  - This paper examines the relationship between experiences with unwanted sexual
      behavior at school and adolescents' health. Adolescent boys and girls (N = 2,808)
      participated in a 1998/1999 survey of secondary school students in two regions of
      The Netherlands. The psychological issues investigated included psychosomatic
      problems and self-esteem. It was hypothesized that adolescents who have
      experienced unwanted sexual behavior at school would report more psychosomatic
      problems and lower self-esteem. Furthermore, it was hypothesized that girls would
      report lower self-esteem and more psychosomatic problems than would boys.
      Regression analysis indicated that experiences with unwanted sexual behavior were
      related to adolescents' psychological health, independently of other variables.

PMID- 15727417
TI  - A work in progress.

PMID- 15727418
TI  - Getting a handle on patient falls.

PMID- 15727419
TI  - Waste away.

PMID- 15727420
TI  - Operating in Iraq.

PMID- 15727421
TI  - Mad no more. Product designed to filter prions.

PMID- 15727422
TI  - Pediatric supratentorial high-grade gliomas.
AB  - The purpose of this review is to highlight some of the pertinent concepts and
      controversies surrounding the diagnosis and treatment of pediatric supratentorial
      high-grade gliomas. Unlike the adult counterparts, pediatric high-grade gliomas
      are likely derived from distinct cytogenetic and molecular alterations. Surgery
      has been shown to play a role in extending patient survival. Some success is
      associated with the provision of chemotherapy. Radiotherapy remains an important
      adjunct in children older than age 3 years. The challenges involved in improving
      the poor prognosis of children in whom these very aggressive tumors have been
      diagnosed will be discussed, as well as some of the novel approaches being
      investigated to improve patient survival and quality of life.

PMID- 15727423
TI  - Convection-enhanced delivery in clinical trials.
AB  - The poor prognosis associated with the current management of malignant gliomas
      has led investigators to develop alternative treatments such as targeted toxin
      therapy. The optimal method for administering these agents is under development
      but appears to be convection-enhanced delivery (CED). The direct intratumoral
      infusion of targeted toxins was first performed in nude mouse flank tumor models
      of human malignant glioma. After the demonstration of in vivo efficacy, these
      potent cytotoxic compounds were tested in Phase I and Phase II clinical trials.
      Using a high-flow microinfusion technique, volumes of up to 180 ml were infused
      by CED through catheters placed directly into brain tumors. Minor systemic
      toxicity was seen in the form of hepatic enzyme elevation. Neural toxicity
      manifested as seizure activity and hemiparesis resulted from peritumoral edema
      that followed the completion of the infusion. Peritumoral toxicity was believed
      to be more related to the concentration of the infused immunotoxin than to the
      infusion volume. In approximately half of patients treated with CED a stable
      disease course, a partial response, or a complete response was demonstrated in
      some clinical trials. Targeted toxin therapy has clinical efficacy in patients
      with malignant gliomas. Convection-enhanced delivery appears to represent an
      effective method for administering these agents in patients with malignant brain
      tumors.

PMID- 15727424
TI  - Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine.
AB  - OBJECT: Therapy of malignant tumors is frequently curtailed by the emergence of
      chemoresistant cell clones. Experimentally, the authors have demonstrated that
      chemotherapy for glioma in rats is markedly improved by the administration of the
      antimutagenic quinacrine. They studied the effects of chloroquine, an
      antimutagenic with an optimal pharmacological profile for human use, as adjuvant
      for the treatment of patients with glioblastoma multiforme (GBM). METHODS: In a
      prospective controlled randomized trial, 18 patients with GBM underwent standard
      treatment with surgery, chemotherapy, and radiotherapy; nine received an
      additional 150-mg dose of chloroquine daily starting 1 day after surgery and
      continued through the observation period. Nine matched patients were included as
      controls. Neuroimaging studies and clinical response were periodically compared.
      The follow-up period ranged from 24 to 50 months. Survival time was defined as
      the main outcome measure. Survival was significantly longer in chloroquine
      treated patients than in controls (33 +/- 5 and 11 +/- 2 months, respectively [p
      < 0.0002]). At the end of the observation period, four patients (46%) treated
      with chloroquine were alive, two had evidence of tumor remission after 2 years;
      in another two, tumor recurrence developed after 2 and 4 years of remission,
      respectively. No control patient survived more than 22 months after surgery.
      CONCLUSIONS: Chronic administration of chloroquine greatly enhanced the response
      of GBM to antineoplastic treatment. Because the cytotoxicity of chloroquine on
      malignant cells is negligible, these favorable results appear mediated by its
      strong antimutagenic effect that precludes the appearance of resistant clones
      during radiotherapy and chemotherapy.

PMID- 15727425
TI  - Okadaic-acid-induced apoptosis in malignant glioma cells.
AB  - OBJECT: Okadaic acid (OA), a potent protein phosphatase inhibitor, has been known
      to induce apoptosis in a variety of cell types. The authors attempted to
      characterize further this model by identifying proteins involved in this form of
      programmed cell death. METHODS: Cellular proliferation was assessed using a
      colorimetric nonradioactive proliferation assay and cell counts. Apoptosis was
      determined by fluorescent microscopy. Activation of the mitogen-activated protein
      kinase (MAPK) pathways was determined by immunoprecipitation of extracellular
      signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38 followed by
      in vitro kinase assays. Western blot analyses were conducted to show inhibitory
      kappaB (IkappaB) phosphorylation and degradation as well as Bax upregulation. The
      binding of nuclear factor-kappaB (NFkappaB) was shown by electrophoretic mobility
      shift assay. Okadaic acid induced cell death in T98G human malignant cell lines
      (50% inhibiting concentration = 20-25 nM). In T98G cells YO-PRO fluorescent
      staining was identified, thus indicating an apoptotic mechanism with a smaller
      percentage of cells undergoing necrotic cell death. Additionally OA induced JNK
      and MAPK activities in a time-dependent manner, increased the expression of Bax,
      and increased IkappaB phosphorylation and NFkappaB activation. There was a
      temporal correlation between these subcellular events and the detection of
      apoptosis morphology in glioma cells. CONCLUSIONS: The authors believe that OA
      acts by blocking dephosphorylation events, thus activating apoptotic pathways
      through ERK and JNK activity. Additionally Bax, IkappaB and NFkappaB may also
      play a role in regulating these pathways.

PMID- 15727426
TI  - Evaluation of factors predicting accurate resection of high-grade gliomas by
      using frameless image-guided stereotactic guidance.
AB  - OBJECT: Frameless image-guided stereotaxy is often used in the resection of high
      grade gliomas. The authors of several studies, however, have suggested that brain
      shift may occur intraoperatively and result in inaccurate resection. To determine
      the usefulness of frameless stereotactic image-guided surgery of high-grade
      gliomas, the authors correlated factors predictive of brain shift, such as tumor
      size, periventricular location, and patient age (as an indicator of brain
      atrophy) with the extent of resection. METHODS: Inclusion criteria included the
      following: 1) stereotactic volumetric craniotomy for resection of tumor; 2)
      histologically proven high-grade glioma; 3) preoperative magnetic resonance (MR)
      imaging demonstration of an enhancing portion of tumor; 4) postoperative MR
      imaging within 48 hours to assess the extent of resection; and 5) preoperative
      intention to perform gross-total resection of the enhancing tumor. Fifty-four
      patients met these criteria between September 1997 and November 2002. Accurate
      resection was considered to be indicated by a lack of nodular enhancement on
      postoperative Gd-enhanced MR images obtained within 48 hours of surgery.
      Frameless stereotactic image-guided surgery resulted in the successful resection
      of 46 (85%) of 54 high-grade gliomas. Accurate resection was significantly more
      likely with tumors less than 30 ml in volume than with those greater than 30 ml
      (93 and 58%, respectively [p < 0.05]). In addition, small periventricular tumors
      were associated with significant less successful resection compared with
      nonperiventricular tumor (77 and 96%, respectively [p = 0.5]). Patient age did
      not affect the likelihood of successful resection. CONCLUSIONS: Frameless image
      guided stereotactic techniques can be reliably used for accurate resection of
      high-grade gliomas when the tumor is less than 30 ml in volume and not adjacent
      to the ventricular system. In cases involving tumors larger in volume or located
      near the ventricles, intraoperative ultrasonography or MR imaging updates should
      be considered.

PMID- 15727427
TI  - Coregistered intraoperative ultrasonography in resection of malignant glioma.
AB  - OBJECT: The authors present their experience with coregistration of preoperative
      imaging data to intraoperative ultrasonography in the resection of high-grade
      gliomas, focusing on methodology and clinical observation. METHODS: Images were
      obtained preoperatively and coregistered to intraoperative hand-held ultrasound
      images by merging the respective imaging coordinate systems. After patient
      registration and imaging calibration, the authors computed the location on the
      magnetic resonance (MR) space of each pixel on an ultrasound image acquired in
      the operating room. The data were retrospectively reviewed in 11 patients with
      high-grade gliomas who underwent ultrasonography-assisted resection at our
      institution between June 2000 and December 2002. Satisfactory coregistration of
      intraoperative ultrasound and preoperative MR images was accomplished in all
      cases. Ultrasound and MR image data were closely congruent. Preoperative setup
      and intraoperative use of the system were unencumbering. CONCLUSIONS: Based on
      these preliminary results, intraoperative ultrasonography is an attractive
      neuronavigational alternative, by which a less expensive and constraining imaging
      technique is used to acquire updated information. Optimal intraoperative guidance
      can be provided by the integration of this with other imaging studies.

PMID- 15727428
TI  - Complications associated with lumbar stenosis surgery in patients older than 75
      years of age.
AB  - OBJECT: An aging population will require that surgeons increasingly consider
      operative intervention in elderly patients. To perform this surgery safely will
      require an understanding of the factors that predict successful outcomes as well
      as complications. METHODS: Records of patients older than the age of 75 years who
      underwent lumbar spinal stenosis surgery were retrospectively reviewed.
      Preexisting medical illnesses were analyzed using the Charlson Weighted
      Comorbidity Index. Ambulatory function was rated on a four-point scale.
      Statistical analysis was performed using a one-tailed t-test with unpaired
      variance. Eighty-eight patients treated between 1994 and 2001 were identified.
      Forty-five percent were women and 52 patients underwent spinal fusion. The follow
      up period averaged 21 months. Back pain was present preoperatively in 89%; after
      surgery 43% experienced complete relief and 33% partial improvement. Leg pain was
      present preoperatively in 98%; after surgery 43% experienced complete relief and
      42% partial improvement. Of the 33 patients with preoperative gait disturbances,
      61% improved at least one point on the ambulatory scale. Wound complications and
      systemic complications were demonstrated in 24 and 16 patients, respectively.
      There were no deaths. Age (p = 0.322), number of fused levels (p = 0.371), and
      the number of laminectomy levels (p = 0.254) were not predictive of
      complications. Length of operative time (p = 0.003) and the Charlson Weighted
      Comorbidity Index score (p = 0.088) were associated with both systemic and wound
      complications. CONCLUSIONS: Surgery in patients older than age 75 years can be
      conducted safely and with similar outcome rates as in younger patients. The
      Charlson Weighted Comorbidity Index score and operative time were predictive of
      the risk of complications.

PMID- 15727429
TI  - Bone grafting.
AB  - In recent years our understanding of spinal fusion biology has improved. This
      includes the continued elucidation of the step-by-step cellular and molecular
      events involved in the prototypic bone induction cascade, as well as the
      identification and characterization of the various critical growth factors
      governing the process of bone formation and bone graft incorporation. Based on
      these fundamental principles, growth factor technology has been exploited in an
      attempt to improve rates of spinal fusion, and promising results have been
      realized in preclinical animal studies and initial clinical human studies. In
      this article the authors review the recent advances in the biology of bone fusion
      and provide a perspective on the future of spinal fusion, a future that will very
      likely include increased graft fusion rates and improved patient outcome as a
      result of the successful translation of fundamental bone fusion principles to the
      bedside.

PMID- 15727430
TI  - Thoracic hemivertebra excision in adults via a posterior-only approach. Report of
      two cases.
AB  - Hemivertebrae are a common cause of congenital scoliosis. Depending on their
      location and the magnitude of the resultant deformity, they may be asymptomatic
      or require treatment. In the past, treatment has focused on prevention of
      deformity progression in growing children. Little has been written about
      congenital scoliosis presenting in adulthood. Because the aging of the spine is a
      kyphosing process and hemivertebrae often present with a local segmental kyphotic
      alignment, this can become symptomatic. Excision of hemivertebrae is well
      established as a safe and effective procedure when treatment is required.
      Initially this was conducted via a combined anterior-posterior approach. Recently
      some authors have indicated that in the lumbar spine hemivertebra resection can
      safely and effectively be achieved via a single posterior transpedicular
      approach. The authors report two adult cases in which they performed posterior
      transpedicular lateral extracavitary excision of a thoracic, fully segmented
      hemivertebrae. Essentially complete correction of the deformity was achieved.
      There were no neurological complications. The patients were spared a thoracotomy
      and no chest tubes were required.

PMID- 15727431
TI  - Atlantooccipital dislocation in children: presentation, diagnosis, and
      management.
AB  - Atlantooccipital dislocation (AOD) injuries are highly unstable, and usually
      result in significant neurological injury and death. Recently the postinjury
      survival period has increased. In a review of the literature the authors found 41
      cases in which survival was greater than 48 hours. This is likely due to improved
      on-scene resuscitation, spinal immobilization, transportation, new diagnostic
      techniques, and a higher index of suspicion. Diagnosis is usually made with plain
      cervical radiographs, but there are shortcomings associated with this modality in
      the pediatric population. Diagnosis is aided by high-resolution computerized
      tomography and magnetic resonance imaging. Infants and toddlers may undergo
      orthotic immobilization alone, whereas older children usually undergo early
      occipital cervical fusion. Those with incomplete AOD may be managed successfully
      with orthotic immobilization.

PMID- 15727432
TI  - Improved nucleic acid triggered probe activation through the use of a 5
      thiomethyluracil peptide nucleic acid building block.
AB  - To improve the efficiency of a nucleic acid triggered probe activation (NATPA)
      system a 5-thiomethyluracil peptide nucleic acid (PNA) building block has been
      synthesized. Attachment of imidazole and a coumarin ester to uracils at the ends
      of two PNAs resulted in a 550 000-fold acceleration of DNA-triggered coumarin
      release relative to imidazole and a 6-fold increase in k(cat) relative to a
      system which had these groups attached to the amino and carboxy ends of PNAs.
      [structure: see text]

PMID- 15727433
TI  - Poly(thiaheterohelicene): a stiff conjugated helical polymer comprised of fused
      benzothiophene rings.
AB  - A novel helical aromatic polymer comprised of fused benzothiophene rings,
      poly(thiaheterohelicene), was synthesized via an intramolecular ring-closing
      reaction with a controlled helicity to one-sided bias. The synthetic helicity
      control involved the induction of the helical conformation and its fixation. The
      ladder polymer showed both an extended pi-conjugation and planarity and a very
      stiff helical structure. [structure: see text]

PMID- 15727434
TI  - Novel lactonization of ethenetricarboxylate derivatives: intermolecular trapping
      of alkenes.
AB  - A novel cyclization of 1,1-diethyl 2-tert-butyl ethenetricarboxylate (1a) in the
      presence of a Lewis acid afforded a 5,5-dimethyl-gamma-lactone derivative 2a. The
      reaction process has been shown to arise from formation by trapping of
      isobutylene generated in situ. Lewis acid-promoted intermolecular reactions of
      1,1-diethyl 2-hydrogen ethenetricarboxylate (5) and various alkenes to afford
      highly functionalized gamma-lactones were also developed. [reaction: see text]

PMID- 15727435
TI  - Synthesis of substituted quinolines by electrophilic cyclization of N-(2
      alkynyl)anilines.
AB  - Quinolines substituted in the 3-position by an iodo or phenylseleno group are
      readily prepared in good to excellent yields by the reaction of propargylic
      anilines with appropriate electrophiles under mild reaction conditions.
      [reaction: see text]

PMID- 15727436
TI  - Aryl annulation of cyclic ketones via a magnesium carbometalation-6-pi-
      electrocyclization protocol.
AB  - A new strategy for the aryl annulation of cyclic ketones is described.
      Palladium(0) coupling of a propargyl alcohol with the enol triflate of a ketone
      and addition of vinylmagnesium chloride generates a triene as a magnesium chelate
      that may be quenched with an electrophile. In some cases, the triene cyclizes
      under the reaction conditions. Aromatization is accomplished by exposure to
      manganese dioxide or dichlorodicyanoquinone (DDQ). [reaction: see text]

PMID- 15727437
TI  - Addition of carbamoylsilanes to electrophilically substituted alkenes.
      Preparation of beta-functionalized tertiary amides.
AB  - The Si-C bond of N,N-dimethylcarbamoylsilanes added regiospecifically to the C=C
      bond of electrophilically functionalized alkenes to afford beta-silyl-beta
      functionalized amides. Carbonyl addition products were formed when hindered
      alkenic esters were used. [reaction: see text]

PMID- 15727438
TI  - Highly regioselective radical cyclizations of allenamides.
AB  - The first radical cyclizations of allenamides are described. These reactions are
      highly regioselective for the central carbon of the allenic moiety, leading to an
      efficient preparation of nitrogen heterocycles such as isoquinolines, and
      carbocycles such as indane and naphthalene derivatives. The exo-cyclization mode
      could also be achieved in some cases, leading to the synthesis of isoindoles. The
      feasibility of a tandem radical cyclization using allenamide is also established.
      [reaction: see text]

PMID- 15727439
TI  - LDA-catalyzed cycloisomerization of 2-(2-propynyloxy)ethyl iodides leading to 3
      (iodomethylene)tetrahydrofurans.
AB  - LDA catalyzes cycloisomerization of 2-(2-propynyloxy)ethyl iodides to give 3
      (iodomethylene)tetrahydrofurans. The reaction is proposed to proceed through a
      mechanism involving exo-cyclization of an alkynyllithium intermediate and
      protonation of the resulting alkylidene carbenoid by the starting iodide.
      [reaction: see text]

PMID- 15727440
TI  - An unexpected two-group migration involving a sulfonynamide to nitrile
      rearrangement. Mechanistic studies of a thermal N --> C tosyl rearrangement.
AB  - We report the discovery of the first double-barreled thermal rearrangement of a
      sulfonynamide and a methoxybenzyl to a nitrile and the first rearrangement of an
      SO(2) group from sulfonamide to ketoimine. The rearrangement occurs under
      surprisingly mild conditions (onset at 100 degrees C in the melt). [reaction: see
      text]

PMID- 15727441
TI  - Hydrocarbon binding inside a hexameric pyrogallol[4]arene capsule.
AB  - Pyrogallol[4]arene forms discrete hexameric capsules in neat normal, branched,
      and cyclic alkanes. These hydrocarbon guests fill the available space and show
      chemical exchange that is slow on the NMR time scale. [reaction: see text]

PMID- 15727442
TI  - Synthesis of thienothiopyranthiones by a new molecular rearrangement.
AB  - On heating with alkynes, the readily prepared 1,3-dithioles 3 undergo a new
      cycloaddition reaction and an unprecedented molecular rearrangement with loss of
      chlorine to give the first 7H-thieno[2,3-c]thiopyran-7-thiones 4 and 4H
      thieno[3,2-c]thiopyran-4-thiones 5 whose structures were confirmed by X-ray
      diffraction. Unexpectedly, the different alkynes used to form 3 and to convert it
      into 4 and 5 were incorporated regiospecifically into the thiophene and thiopyran
      rings, respectively. [reaction: see text]

PMID- 15727443
TI  - A general synthetic route to indenofluorene derivatives as new organic
      semiconductors.
AB  - A series of 2,6-disubstituted indenofluorene derivatives were obtained in high
      purity via a general route involving the Suzuki coupling reaction. The potential
      of these conjugated indenofluorenes as new organic semiconductors was
      demonstrated by the light-emitting diode reaching a high luminance of 1400
      Cd/m(2) below 10 V. [structure: see text]

PMID- 15727444
TI  - Nonracemic homopropargylic alcohols via asymmetric allenylboration with the
      robust and versatile 10-TMS-9-borabicyclo[3.3.2]decanes.
AB  - The asymmetric allenylboration of representative aldehydes with the stable,
      storable 1 is reported. Easily and efficiently prepared in either enantiomeric
      form from the air-stable crystalline 4 through simple Grignard procedures, 1
      gives 6 cleanly. The latter is easily isolated in high yield and ee with
      predictable stereochemistry. The procedure also regenerates 4 for its direct
      conversion back to 1 and facilitates the efficient recovery of the
      pseudoephedrine. The net process is the synthetic equivalent of the asymmetric
      addition of allenylmagnesium bromide to aldehydes. [reaction: see text]

PMID- 15727445
TI  - The origin of cooperativity in double-wheel receptors. Freezing of internal
      rotation or ligand-induced torsional strain?
AB  - A model is proposed for the homotropic cooperative binding of a ditopic ligand to
      a double-wheel receptor with the aim of understanding the origin of
      cooperativity. Application of the model to the case of Ce(IV) bisporphyrinate
      double-decker complexes indicates that cooperativity is mainly due to ligand
      induced torsional strain. [structure: see text]

PMID- 15727446
TI  - Supramolecular control of oligothienylenevinylene-fullerene interactions:
      evidence for a ground-state EDA complex.
AB  - Complementary hydrogen-bonding interactions between a barbituric acid-substituted
      fullerene derivative (1) and corresponding receptor (2) bearing
      thienylenevinylene units are used to assemble a 1:1 supramolecular complex (K =
      5500 M(-1)). Due to the close proximity of the redox-active moieties within the
      assembly, strong ground-state electron-donor-acceptor interactions are observed.
      Photoinduced electron transfer from electron-rich thienylenevinylene subunits to
      the fullerene is very fast (k(et) = 5.5 x 10(12) s(-1)), as determined by fs-time
      resolved transient absorption spectroscopy. [reaction: see text]

PMID- 15727447
TI  - Preparation of sterically congested di(4-pyridyl)diazomethanes and
      characterization of triplet carbenes from them.
AB  - Di(4-pyridyl)diazomethanes having two and four ortho chlorine groups were
      prepared, and the triplet carbenes generated from them were characterized by ESR
      and UV/vis at low temperature and time-resolved UV/vis at room temperature. An
      appreciable increase in the stability of triplet carbenes is achieved by
      introducing ortho chlorine groups. [structure: see text]

PMID- 15727448
TI  - Synthesis of alpha-kainic acid from a 7-azabicyclo[2.2.1]heptadiene by tandem
      radical addition-homoallylic radical rearrangement.
AB  - Reductive radical addition of 2-iodoethanol to N-Boc 2-tosyl-7
      azabicyclo[2.2.1]heptadiene gives N-Boc syn-7-(2-hydroxyethyl)-4-tosyl-2
      azabicyclo[2.2.1]hept-5-ene, which is converted into the neuroexcitants 3
      (carboxymethyl)pyrrolidine-2,4-dicarboxylic acid and alpha-kainic acid.
      [structure: see text]

PMID- 15727449
TI  - Stereoselective synthesis of cyercene A and the placidenes.
AB  - Members of a family of alpha-methoxy-gamma-pyrone-containing polypropionate
      natural products have been stereoselectively synthesized. Two key iodovinyl
      pyrone building blocks were coupled to appropriately selected vinyl stannanes to
      assemble the highly substituted polyene side chains of the natural products.
      [structure: see text]

PMID- 15727450
TI  - DYKAT of vinyl aziridines: total synthesis of (+)-pseudodistomin D.
AB  - A concise total synthesis of (+)-pseudodistomin D was developed. The absolute
      stereochemistry was established through a dynamic kinetic asymmetric
      cycloaddition of an isocyanate to a vinyl aziridine. The piperidine core was
      constructed through a silver(I)-catalyzed hydroamination of an alkyne and
      subsequent diastereo- and regioselective reduction. [reaction: see text]

PMID- 15727451
TI  - Contribution to the study of the mechanism of directed remote-metalation.
      Evidence for the intermediacy of a geminal dimetallo dialkoxide C(OM)2 (M = Li,
      K), first doubly charged director of ortho metalation.
AB  - The mechanism of the metalation of 2-biphenyl carboxylic acid (1) with the
      Lochmann-Schlosser superbase was determined by deuteriolysis. Both ortho (C(3))
      and remote (C(2')) positions are metalated. The C(2')-metalated species 2
      cyclizes instantaneously. Under suitable conditions, the doubly charged geminal
      dimetallo dialkoxide group C(OM)(2) 4 directs metalation in the adjacent position
      (C(1)), affording a stable 1-metallo-9H-fluorene-9,9-dimetallo dialkoxide 5 that
      can be trapped by diverse electrophiles to give 1-substituted 9H-fluoren-9-ones 7
      and 9 after acidic workup. [structure: see text]

PMID- 15727452
TI  - PS-COD and PS-9-BBN: polymer-supported reagents for solution-phase parallel
      synthesis.
AB  - 1,5-Cyclooctadiene was deprotonated under LICKOR conditions and reacted with
      Merrifield resin to afford an immobilized cyclooctadiene in high yield. This
      polymer is effective as a halogen scavenger, while hydroboration leads to a
      supported 9-BBN analogue. The latter exhibits similar regioselectivity to 9-BBN
      in olefin hydroboration. [reaction: see text]

PMID- 15727454
TI  - A new synthesis of gamma-lactams based on the reaction of vinyl sulfilimines with
      dichloroketene.
AB  - The reactions of several aryl-, furanyl-, and vinyl substituted sulfilimines with
      dichloroketene proceeded at 25 degrees C to yield thioalkyl substituted gamma
      lactams which, in turn, were converted to a variety of nitrogen-containing
      substrates. [reaction: see text]

PMID- 15727453
TI  - Synthesis of 14-azacamptothecin, a water-soluble topoisomerase I poison.
AB  - 14-Azacamptothecin, a potent, water-soluble analogue of the antitumor agent
      camptothecin, has been prepared by a convergent synthesis. The key condensation
      of the AB and DE rings with concomitant formation of ring C of 14-aza CPT was
      carried out in two stages, the latter of which involved a radical cyclization
      strategy. [structure: see text]

PMID- 15727455
TI  - Pentafluorophenyl sulfonate ester as a protecting group for the preparation of
      biaryl- and heterobiaryl sulfonate esters.
AB  - The use of the pentafluorophenyl (PFP) group as a sulfonic acid protecting group
      has allowed the synthesis of new biaryl- and heterobiaryl-PFP-sulfonate esters by
      use of the Suzuki-Miyaura reaction. The successful employment of a novel
      inorganic base, anhydrous sodium tetraborate, was crucial to give the products in
      excellent yields. The PFP-sulfonate ester has been previously shown to be an
      excellent alternative to sulfonyl chlorides in the synthesis of sulfonamides.
      [structure: see text]

PMID- 15727456
TI  - Short and efficient synthesis of a vinyl-substituted tricyclic erythromycin
      derivative.
AB  - Tricyclic erythromycin A derivatives are known potent antibacterial agents, but
      the potential of substituted tricyclic erythromycin A derivatives remains largely
      unexplored. To study this lead, the tricyclic ring system was synthesized by an
      efficient three-step synthesis starting from the allylic alcohol utilizing a
      novel azidoisocyanate. These tricyclic analogues can be used as scaffolds to
      probe secondary ribosomal binding sites. [structure: see text]

PMID- 15727457
TI  - Microwave-assisted regioselective addition of P(O)-H bonds to alkenes without
      added solvent or catalyst.
AB  - The addition of P(O)-H bonds to alkenes has been accomplished using microwave
      irradiation in the absence of added solvent and catalyst. In addition to single
      addition reactions, tandem hydrophosphinylation reactions with alkynes afforded
      unsymmetrical species such as phosphine oxide-phosphinates. [reaction: see text]

PMID- 15727458
TI  - NBS-catalyzed hydroamination and hydroalkoxylation of activated styrenes.
AB  - N-Bromosuccinimide efficiently catalyzes the hydroamination and hydroalkoxylation
      of activated styrenes using tosylamides, carbamates, and alcohols as the
      nucleophiles to afford amino and ether derivatives, respectively. Both the
      processes give good to excellent yields of the products with 100%
      regioselectivity (Markovnikov fashion). [structure: see text]

PMID- 15727459
TI  - Simple modification in hexakis-addition for efficient synthesis of c(60)-centered
      dendritic molecules bearing multiple aromatic chromophores.
AB  - In the templated hexakis-addition reaction of malonic esters with C(60) to
      prepare dendritic macromolecules that are terminated symmetrically with 12
      derivatized pyrenes, a simple modification to use a much larger excess of the
      bromination agent resulted in dramatic increases in the product yields.
      [structure: see text]

PMID- 15727460
TI  - Microwave-assisted sequential amide bond formation and intramolecular amidation:
      a rapid entry to functionalized oxindoles.
AB  - A general method has been developed for the synthesis of N-substituted oxindoles.
      The two-step process involves initial microwave-assisted amide bond formation
      between 2-halo-arylacetic acids and various alkylamines and anilines, followed by
      a palladium-catalyzed intramolecular amidation under aqueous conditions. In the
      case of alkylamines, the procedure can be carried out as a one-pot process
      without isolation of the intermediate amide. [structure: see text]

PMID- 15727462
TI  - Lewis acid assisted ring-closing metathesis of chiral diallylamines: an efficient
      approach to enantiopure pyrrolidine derivatives.
AB  - Lewis acid assisted ring-closing olefin metathesis (RCM) of chiral diallylamines,
      using the second generation RCM ruthenium-based catalyst, leads to enantiopure
      pyrrolidine derivatives in 79-93% yields under very mild conditions. The scope of
      the olefin metathesis has been expanded. [structure: see text]

PMID- 15727461
TI  - Total synthesis of LFA-1 antagonist BIRT-377 via organocatalytic asymmetric
      construction of a quaternary stereocenter.
AB  - A catalytic route for enantioselective total synthesis of cell adhesion inhibitor
      BIRT-377 is described. The quaternary stereocenter was constructed through l
      proline-derived, tetrazole-catalyzed direct asymmetric alpha-amination of 3-(4
      bromophenyl)-2-methylpropanal with dibenzyl azodicarboxylate. In the course of
      these studies, a one-pot trifluoro acetylation/selective benzyloxycarbonyl
      deprotection method was developed. [structure: see text]

PMID- 15727463
TI  - Total synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine
      B).
AB  - Starting from L-serine, a stereoselective synthesis of pachastrissamine, a
      structurally novel anhydrosphingosine derivative, is reported in this Letter.
      [structure: see text]

PMID- 15727464
TI  - Rapid microwave-assisted solid-phase glycopeptide synthesis.
AB  - Coupling of glycosylated Fmoc-Thr or Fmoc-Ser with N-terminal amino acids on a
      resin proceeded smoothly under microwave irradiation for 20 min with much higher
      efficiency (98% yield per coupling) than found in more general conditions.
      Compared with a conventional protocol, the present method greatly reduces the
      time required for solid-phase glycopeptide synthesis from 4 days to 7 h, as is
      the case with the synthesis of Muc-1-related 20-residue glycopeptide carrying
      five core-2 trisaccharide chains. [structure: see text]

PMID- 15727465
TI  - Transtaganolides A-D: novel metabolites from Thapsia transtagana.
AB  - Four novel and unusual C-19 compounds from Thapsia transtagana, named
      transtaganolides A-D, have been isolated. Their structures were established by
      physical methods, including X-ray analysis of transtaganolides A and B. This is
      the first time that a 7-methoxy-4,5-dihydro-3H-oxepin-2-one ring has been found
      in a natural product. [structure: see text]

PMID- 15727467
TI  - Ratiometric and selective fluorescent sensor for CuII based on internal charge
      transfer (ICT).
AB  - A Cu(II)-sensing, ratiometric, and selective fluorescent sensor 1, N-butyl-4,5
      di[(pyridin-2-ylmethyl)amino]-1,8-naphthalimide, was designed and synthesized on
      the basis of the mechanism of internal charge transfer (ICT). In aqueous ethanol
      solutions of 1, the presence of Cu(II) induces the formation of a 1:1 metal
      ligand complex, which exhibits a strong, increasing fluorescent emission centered
      at 475 nm at the expense of the fluorescent emission of 1 centered at 525 nm.
      [structure: see text]

PMID- 15727468
TI  - Diastereoselective aldol additions to alpha-amino-beta-silyloxy aldehydes.
      Divergent synthesis of aminodiols.
AB  - A divergent protocol for substrate-controlled diastereoselective synthesis of
      aminodiols has been developed using nucleophilic Mukaiyama aldol additions to
      alpha-amino-beta-silyloxy aldehydes. The merged stereochemical impact on the
      diastereoselectivity of the polar alpha- and beta-substituents is highlighted.
      [reaction: see text]

PMID- 15727466
TI  - A highly efficient synthesis of the FGH ring of micrandilactone A. Application of
      thioureas as ligands in the Co-catalyzed Pauson-Khand reaction and Pd-catalyzed
      carbonylative annulation.
AB  - The functionalized FGH ring system of micrandilactone A was successfully
      constructed in high selectivity and good yields. The key reactions in our
      strategy are the Co-thiourea-catalyzed stereoselective, intramolecular Pauson
      Khand reaction and Pd-thiourea-catalyzed stereoselective, intramolecular
      annulation. [structure: see text]

PMID- 15727469
TI  - Sulfur dioxide-mediated syntheses of polyfunctional alkenes and (E,Z)- and (E,E)
      2,4-dien-1-ones.
AB  - Efficient methods for the stereoselective synthesis of polyfunctional (E)- and
      (Z)-alkenes and conjugated (E,E)- and (E,Z)-dienones are presented. They rely
      upon one-pot, four-component processes that condense 1-oxy-1,3-dienes, silyl enol
      ethers, SO2, and carbon electrophiles. [structure: see text]

PMID- 15727470
TI  - Enantioselective Friedel-Crafts alkylation reactions catalyzed by a chiral
      nonracemic C2-symmetric 2,2'-bipyridyl copper(II) complex.
AB  - Enantioselective Friedel-Crafts alkylation reactions of a series of substituted
      indoles with methyl trifluoropyruvate, catalyzed by a chiral nonracemic C(2)
      symmetric 2,2'-bipyridyl copper(II) triflate complex, are described. The
      corresponding 3,3,3-trifluoro-2-hydroxy-2-indole-3-yl-propionic acid methyl
      esters were formed in good yield and in high enantiomeric excess (up to 90%).
      This is the first report of the use of a chiral nonracemic 2,2'-bipyridyl ligand
      in catalytic and enantioselective Friedel-Crafts alkylation reactions. The
      structural characterization of a copper(II) chloride complex of the chiral 2,2'
      bipyridyl ligand by X-ray crystallography is also presented. [reaction: see text]

PMID- 15727471
TI  - Conversion of alpha,beta-unsaturated aldehydes into saturated esters: an Umpolung
      reaction catalyzed by nucleophilic carbenes.
AB  - N-Heterocyclic carbenes derived from benzimidazolium salts are effective
      catalysts for generating homoenolate species from alpha,beta-unsaturated
      aldehydes. These nucleophilic intermediates can be protonated, and the resulting
      activated carbonyl unit is trapped with an alcohol nucleophile, thereby promoting
      a highly efficient conversion of an alpha,beta-unsaturated aldehyde into a
      saturated ester. A kinetic resolution of secondary alcohols can be achieved using
      chiral imidazoylidene catalysts. [reaction: see text]

PMID- 15727472
TI  - Stereoselective synthesis of multisubstituted alkenes via conformationally labile
      alkenyllithium species.
AB  - Stereoselective synthesis of tri- and tetrasubstituted alkenylsilanes has been
      realized by the selective intramolecular silicon migration in the rapidly
      equilibrating alkenyllithium species. Subsequent copper- and palladium-mediated
      coupling with allyl and aryl halides provides tri- and tetrasubstituted alkenes
      possessing all different carbon-substituents with complete stereoselectivity.
      [structure: see text]

PMID- 15727473
TI  - Stereocontrolled synthesis of angularly substituted 1-azabicyclic rings by
      cationic 2-aza-cope rearrangements.
AB  - A new synthesis of 1-azabicyclic molecules having angular substitution is
      reported. This method can be employed to prepare a range of 1-azabicylic rings,
      including ones containing vicinal quaternary carbon centers and three contiguous
      stereocenters. [structure: see text]

PMID- 15727474
TI  - Sterically stabilized cyclopropenonophanes and an electronically stabilized
      cyclopropenethionophane: syntheses, structural properties, and reactivity.
AB  - The syntheses of sterically stabilized cyclopropenonophanes as well as an
      electronically stabilized cyclopropenethionophane are reported, and their
      molecular structures in the solid state are elucidated. The sulfur of the CS
      moiety in cyclopropenethiones was shown to react as a nucleophile. Temperatures
      of more than 240 degrees C favor the extrusion of CO in the cyclopropenonophane
      to afford an alpha,alpha'-tetramethyl-substituted cyclodiyne. [reaction: see
      text]

PMID- 15727475
TI  - Functionalization of alpha,beta-unsaturated esters and ketones: a facile and
      highly stereoselective one-pot approach to N-protected alpha,beta-dehydroamino
      acid derivatives.
AB  - A new, facile, and highly stereoselective protocol toward alpha,beta-dehydroamino
      acid derivatives has been developed. The one-pot synthesis was very convenient to
      perform by using the aminohalogenation reaction of alpha,beta-unsaturated esters
      and ketones followed by treatment with specific bases. Only two [2.2.2] bicyclic
      organic bases were found to be effective for this transformation. Good yields (58
      68%) and excellent Z-selectivity were obtained for 12 examples. [reaction: see
      text]

PMID- 15727476
TI  - Rapid and efficient synthesis of 1,2,4-oxadiazoles utilizing polymer-supported
      reagents under microwave heating.
AB  - 1,2,4-Oxadiazoles can be rapidly and efficiently synthesized from a variety of
      readily available carboxylic acids and amidoximes using either method A or method
      B. The use of commercially available polymer-supported reagents combined with
      microwave heating resulted in high yields and purities of the product 1,2,4
      oxadiazoles in an expeditious manner. [structure: see text]

PMID- 15727477
TI  - Extending Pummerer reaction chemistry. Synthesis of (+/-)-dibromophakellstatin by
      oxidative cyclization of an imidazole derivative.
AB  - The diastereoselective oxidative cyclization of a dihydrooroidin derivative is
      reported. The thioimidate product formed by application of a new variant of the
      Pummerer reaction serves as a precursor to dibromophakellstatin. [reaction: see
      text]

PMID- 15727478
TI  - Toward an enantioselective total synthesis of sarain A: construction of an
      advanced intermediate and rearrangement of the sarain A core under mild
      conditions.
AB  - A high-yielding N-sulfonyliminium ion-enoxysilane cyclization and a ring-closing
      metathesis are key steps in the enantioselective synthesis of late-stage
      intermediates en route to sarain A. Also revealed is an unprecedented
      rearrangement of the tetracyclic sarain A core under mildly acidic conditions.
      [structure: see text]

PMID- 15727479
TI  - Asymmetric synthesis of (+)-(S,S)-reboxetine via a new (S)-2
      (hydroxymethyl)morpholine preparation.
AB  - (S,S)-Reboxetine was synthesized stereospecifically in 30% overall yield and 99%
      ee in eight steps. Key steps were selective oxidation of an N-protected
      hydroxymethylmorpholine and aryl-chromium-mediated aromatic nucleophilic
      substitution. [structure: see text]

PMID- 15727480
TI  - A concise stereoselective route to the indoline spiroaminal framework of
      neoxaline and oxaline.
AB  - The stereoselective synthesis of tetracyclic intermediate, the indoline
      spiroaminal 3 for neoxaline (1) and oxaline (2), has been accomplished. The key
      step of the stereoselective synthesis of 3 was the Lewis acid mediated
      transcyclization of 4 to the diaminal 18, and the tungstate-catalyzed oxidation
      of 18 to obtain the nitrone 19, which easily cyclizes to the indoline spiroaminal
      framework 3. [structure: see text]

PMID- 15727481
TI  - Suzuki-Miyaura cross-coupling of benzylic carbonates with arylboronic acids.
AB  - The cross-coupling of benzylic carbonates with arylboronic acids gave the
      corresponding diarylmethanes in high yields by use of the palladium catalyst
      generated in situ from [Pd(eta(3)-C(3)H(5))Cl](2) and 1,5
      bis(diphenylphosphino)pentane (DPPPent). The Suzuki-Miyaura reaction using
      DPPPent-palladium catalyst is applicable to syntheses of a broad range of
      functionalized diarylmethanes. [reaction: see text]

PMID- 15727482
TI  - A Cyclopropabenzenylidenethenone (propadienone) via a new route to
      alkylidenecycloproparenes.
AB  - Reaction of 1,1-dichloro-2,5-diphenylcyclopropabenzene 6 with Meldrum's acid 8 in
      the presence of pyridine leads to coupling of the cycloproparenyl cation 7 with
      the stabilized diketo anion 9. Subsequent, spontaneous, base-induced
      dehydrochlorination gives the alkylidenecyclopropabenzene 11 in a one-pot
      reaction. Flash vacuum thermolysis of 11 at 650 degrees C ejects acetone and
      carbon dioxide, giving cyclopropabenzenylidenethenone 12 that is isolated in an
      Ar matrix at 20 K and characterized by a strong ketene band at 2107 cm(-1) in the
      IR spectrum. [reaction: see text]

PMID- 15727483
TI  - Diastereoselective synthesis of pyrrolidines using a nitrone/cyclopropane
      cycloaddition: synthesis of the tetracyclic core of nakadomarin A.
AB  - The synthesis of the tetracyclic core of nakadomarin A is described. The core
      contains all the heterocycles and the required stereocenters found in the natural
      product and provides a promising route to the target itself. The strategy
      utilizes a general, diastereoselective pyrrolidine synthesis that proceeds via a
      homo 3 + 2 dipolar cycloaddition. The scope of this methodology is also
      described. [structure: see text]

PMID- 15727485
TI  - The epidemiologic approach to pharmacogenomics.
AB  - The epidemiologic approach enables the systematic evaluation of potential
      improvements in the safety and efficacy of drug treatment which might result from
      targeting treatment on the basis of genomic information. The main epidemiologic
      designs are the randomized control trial, the cohort study, and the case-control
      study, and derivatives of these proposed for investigating gene-environment
      interactions. However, no one design is ideal for every situation, and
      methodological issues, notably selection bias, information bias, confounding and
      chance, all play a part in determining which study design is best for a given
      situation. There is also a need to employ a range of different designs to
      establish a portfolio of evidence about specific gene-drug interactions. In view
      of the complexity of gene-drug interactions, pooling of data across studies is
      likely to be needed in order to have adequate statistical power to test
      hypotheses. We suggest that there may be opportunities (i) to exploit samples
      from trials already completed to investigate possible gene-drug interactions;
      (ii) to consider the use of the case-only design nested within randomized
      controlled trials as a possible means of reducing genotyping costs when
      dichotomous outcomes are being investigated; and (iii) to make use of population
      based disease registries that can be linked with tissue samples, treatment
      information and death records, to investigate gene-treatment interactions in
      survival.

PMID- 15727486
TI  - Pharmacogenomics of fluorouracil, irinotecan, and oxaliplatin in hepatic
      metastases of colorectal cancer: clinical implications.
AB  - Hepatic metastases occur in about half of patients with colorectal cancer. Since
      hepatic metastases are often not accessible for surgery, chemotherapy of
      metastases is important. The most commonly used chemotherapy drugs for hepatic
      metastases are fluorouracil, irinotecan, and oxaliplatin. Several enzymes are
      known to be involved in the catabolism and anabolism of these drugs, and the
      activity of these enzymes varies greatly between individuals. The causes of this
      variation include genetic polymorphisms, different regulation between normal and
      cancer tissue, and the influence of chemotherapy on enzyme expression. The
      varying enzyme activity may have an important effect on the outcome of
      chemotherapy. Several studies confirm the influence of the activity of
      thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase
      on the outcome of fluorouracil therapy for colorectal cancer, with higher enzyme
      activities predicting lower treatment efficacy. Although fewer studies are
      available regarding therapy of hepatic metastases, the same relationship between
      thymidylate synthase activity and outcome of fluorouracil therapy observed for
      primary colorectal cancer was found. For the other two enzymes, only a few
      studies are available, but the results indicate similarly that higher enzyme
      activity seems to be disadvantageous. The enzymes responsible for the activation,
      metabolism and mechanism of action of irinotecan, namely carboxylesterase 2,
      cytochrome P450 (CYP) 3A4, uridine diphosphate glucuronosyltransferase isoform
      1A1 (UGT1A1), and topoisomerase-I, also exhibit variable interindividual
      activity. Thus, there may be an association between enzyme activity and response
      to therapy. For instance, in patients with colorectal cancer, higher enzyme
      activity of topoisomerase-I seems to be predictive of a better response to
      irinotecan. CYP3A4 and UGT1A1 activity levels might be predictive of irinotecan
      toxicity rather than efficacy. The degradation of oxaliplatin is independent of
      potentially varying enzyme activity, but for this drug, the DNA repair enzyme
      ERCC1 may influence the survival time after chemotherapy. Taken together, the
      available data indicate the importance of the different enzyme activities on the
      outcome of chemotherapy of hepatic metastases in colorectal cancer. More
      information is needed, especially for the newer drugs irinotecan and oxaliplatin.
      However, the existing data are very promising in respect to the potential to
      guide dose and drug selection for more efficient and less toxic chemotherapy of
      hepatic metastases.

PMID- 15727487
TI  - Advances in myeloma genetics and prospects for pharmacogenomic testing in
      multiple myeloma.
AB  - Pharmacogenomic studies in multiple myeloma, a neoplasia of clonally expanded
      malignant bone marrow plasma cells, are helping to set the stage for
      individualized therapy. Although relatively few in numbers, these studies are
      already providing new therapeutic targets and avenues for drug discoveries as
      well as contributing to novel prognostic markers in multiple myeloma. High
      throughput mutation screening of the kinome promises to identify further novel
      targets for therapy. Genetics and gene expression profiling technology have
      improved molecular-based patient stratification and prognostic staging, expanded
      knowledge of the molecular mechanism of chemotherapeutic agents, and provided a
      better understanding of myeloma bone disease. The use of pharmacogenomic
      strategies in myeloma is thus already changing medical practice.

PMID- 15727488
TI  - Monoamine oxidase a and tryptophan hydroxylase gene polymorphisms: are they
      associated with bipolar disorder?
AB  - Most of the candidate gene studies in bipolar disorder have focused on the major
      neurotransmitter systems that are influenced by drugs used in the treatment of
      this disorder. The monoamine oxidase A (MAOA) and the tryptophan hydroxylase
      (TPH1, TPH2) genes are two of the candidates that have been tested in a series of
      association studies using unrelated or family-based controls. This review
      summarizes the existing association studies regarding these genes. Most of these
      studies were based on the unrelated case-control design with samples of 50 to 600
      subjects. Regarding MAOA, three meta-analyses with partially overlapping samples
      supported a modest effect of this gene in bipolar disorder in female Caucasians.
      However, as several studies could not replicate these findings, more work is
      necessary to demonstrate unequivocally the involvement of MAOA in bipolar
      disorder and establish the biological mechanism underlying the genetic
      association. With respect to TPH1 and TPH2, the majority of studies did not
      provide evidence for an association between these genes and bipolar disorder. The
      genes are more likely to be related to suicidal behavior than to bipolar
      disorder.

PMID- 15727489
TI  - Pharmacogenomics and the drug discovery pipeline: when should it be implemented?
AB  - One of the key factors in developing improved medicines lies in understanding the
      molecular basis of the complex diseases we treat. Investigation of genetic
      associations with disease utilizing advances in linkage disequilibrium-based
      whole genome association strategies will provide novel targets for therapy and
      define relevant pathways contributing to disease pathogenesis. Genetic studies in
      conjunction with gene expression, proteomic, and metabonomic analyses provide a
      powerful tool to identify molecular subtypes of disease. Using these molecular
      data, pharmacogenomics has the potential to impact on the drug discovery and
      development process at many stages of the pipeline, contributing to both target
      identification and increased confidence in the therapeutic rationale. This is
      exemplified by the identified association of 5-lipoxygenase-activating protein
      (ALOX5AP/FLAP) with increased risk of myocardial infarction, and of the chemokine
      receptor 5 (CCR5) with HIV infection and therapy. Pharmacogenomics has already
      been used in oncology to demonstrate that molecular data facilitates assessment
      of disease heterogeneity, and thus identification of molecular markers of
      response to drugs such as imatinib mesylate (Gleevec) and trastuzumab
      (Herceptin). Knowledge of genetic variation in a target allows early assessment
      of the clinical significance of polymorphism through the appropriate design of
      preclinical studies and use of relevant animal models. A focussed pharmacogenomic
      strategy at the preclinical phase of drug development will produce data to inform
      the pharmacogenomic plan for exploratory and full development of compounds.
      Opportunities post-approval show the value of large well-characterized data sets
      for a systematic assessment of the contribution of genetic determinants to
      adverse drug reactions and efficacy. The availability of genomic samples in large
      phase IV trials also provides a valuable resource for further understanding the
      molecular basis of disease heterogeneity, providing data that feeds back into the
      drug discovery process in target identification and validation for the next
      generation of improved medicines.

PMID- 15727490
TI  - Bayesian decomposition analysis of bacterial phylogenomic profiles.
AB  - BACKGROUND: The past two decades have seen the appearance of new infectious
      diseases and the reemergence of old diseases previously thought to be under
      control. At the same time, the effectiveness of the existing antibacterials is
      rapidly decreasing due to the spread of multidrug-resistant pathogens. AIM: The
      aim of this study was to the identify candidate molecular targets (e.g. enzymes)
      within essential metabolic pathways specific to a significant subset of bacterial
      pathogens as the first step in the rational design of new antibacterial drugs.
      METHODS: We constructed a dataset of phylogenomic profiles (vectors that encode
      the similarity, measured by BLAST scores, of a gene across many species) for a
      series of 31 pathogenic bacteria of interest with 1073 genes taken from the
      reference organisms Escherichia coli and Mycobacterium tuberculosis. We applied
      Bayesian Decomposition, a matrix decomposition algorithm, to identify functional
      metabolic units comprising overlapping sets of genes in this dataset. RESULTS:
      Although no information on phylogeny was provided to the system, Bayesian
      Decomposition retrieved the known bacteria phylogenic relationships on the basis
      of the proteins necessary for survival. In addition, a set of genes required by
      all bacteria was identified, as well as components and enzymes specific to
      subsets of bacteria. CONCLUSION: The use of phylogenomic profiles and Bayesian
      Decomposition provide important insights for the design of new antibacterial
      therapeutics.

PMID- 15727491
TI  - Understanding academic attitudes and achievement in mexican-origin youths: ethnic
      identity, other-group orientation, and fatalism.
AB  - This study tested the relationships among ethnic identity, other-group
      orientation, fatalism, and 2 dependent variables: attitude toward education and
      school, and grade point average (GPA). Mexican-origin adolescents (N = 222)
      completed the Multigroup Ethnic Identity Measure (J. S. Phinney, 1992), the
      fatalism scale of the Multiphasic Assessment of Cultural Constructs-Short Form
      (I. Cuellar, B. Arnold, & G. Gonzalez, 1995), and the attitude scale of the
      Learning and Study Strategies Inventory-High School (C. E. Weinstein & D. R.
      Palmer, 1990a). Other-group orientation was positively related to attitude and
      GPA, and a negative relationship between fatalism and attitude was demonstrated.
      No relationship emerged between ethnic identity and the dependent variables.

PMID- 15727492
TI  - Age of first onset major depression in Chinese Americans.
AB  - Using data from the Chinese American Epidemiological Study, risk for experiencing
      an initial episode of major depression across the life course was examined. Data
      were collected on 1,747 U.S.-born and foreign-born Chinese Americans (ages 18-65
      years). Results suggest that Chinese American women did not evidence higher risk
      than Chinese American men for experiencing a 1st major depressive episode. Risk
      for experiencing a 1st depressive episode decreased as length of residence in the
      United States increased. Although those who immigrated at younger ages evidenced
      greater overall risk, those who came at later ages were more likely to become
      depressed at or soon after arrival. Competing theories of acculturation-related
      risk are discussed and directions for future research are proposed.

PMID- 15727493
TI  - Examining African self-consciousness and Black racial identity as predictors of
      Black men's psychological well-being.
AB  - This study investigated African self-consciousness and Black racial identity as
      predictors of psychological distress and self-esteem for Black men. One hundred
      thirty Black men from a college and community sample completed the African Self
      Consciousness Scale, the Racial Identity Attitude Scale-B, the Symptom Checklist
      90-Revised, and the Coopersmith Self-Esteem Inventory. Canonical correlation
      analysis found 2 significant roots with the 1st root indicating that Black men
      whose attitudes reflected Preencounter and Immersion racial identity attitudes
      and who do not resist against anti-African/Black forces reported greater
      psychological distress and less esteem. Results from the 2nd root suggested that
      Black men whose attitudes reflect greater Internalization racial identity
      attitudes, greater resistance to anti-African/Black forces, and less
      identification with Blacks reported greater self-esteem.

PMID- 15727494
TI  - A confirmatory model for depression among Japanese American and part-Japanese
      American adolescents.
AB  - A confirmatory model integrating Japanese ethnicity, cultural identity, and
      depression was developed (N = 140). The model incorporated the Center for
      Epidemiologic Studies-Depression Scale (CES-D), Major Life Events Scale, and
      Japanese Cultural Scale. Japanese American adolescents scored higher on the
      Japanese Cultural Scale and reported fewer depressive symptoms on the CES-D total
      and on 2 of the 3 CES-D factors than part-Japanese American adolescents.
      Predictors for depression were being Japanese American vs. part-Japanese
      American, female gender, and culturally intensified events. A significant
      interaction of behavior by self-identification was noted. The model had good
      overall fit and suggested that the formation of cultural identity may contribute
      to depressive symptoms experienced by adolescents, particularly adolescents of
      mixed heritage.

PMID- 15727495
TI  - Effects of perceived parental school support and family communication on
      delinquent behaviors in latinos and white non-latinos.
AB  - The authors examined the roles of perceived parental school support and family
      communication in the context of delinquent behaviors in Mexican American and
      White non-Latino adolescents. Family communication was defined as the degree to
      which adolescents endorsed that they communicated with their parents about a
      variety of topics. The Parental School Support scale was administered to assess
      adolescents' perceptions of parental support for academic pursuits. Data analysis
      included the relationship between these variables and their predictive
      relationship to delinquency, and the relationship to gender and ethnicity.
      Results demonstrated that adolescents' perceptions of family communication and
      parental school support were related to the likelihood of committing delinquent
      acts. There were no significant differences in gender or ethnicity in perceived
      levels of family communication and parental school support.

PMID- 15727496
TI  - Toward a meaningful spirituality for people of color: lessons for the counseling
      practitioner.
AB  - This article attempts to capture a significant aspect of the counseling process
      for people of color: the spiritual dimension. It is argued that spirit and
      spirituality are relevant dimensions that should be integrated in counseling
      because spirituality is a key ingredient in the cultural upbringing and
      socialization of many people of color. Further, religious and spiritual beliefs
      are affected by experiences of racism and oppression, which then affects
      psychological coping. Reflective guidelines are offered to understand the essence
      of spirituality and cultural diversity, and lessons for the practitioner are
      recommended.

PMID- 15727497
TI  - The racial identity and cultural orientation of Lumbee American Indian high
      school students.
AB  - The uncertain and complex lineage of the Lumbee American Indian tribe has made
      the issue of identity of prime concern. The cultural identification, racial
      identification, bicultural competence, and perceived school environment for 103
      Lumbee Indian high school students were examined in this study. Higher self
      ratings on American Indian cultural competence and American Indian cultural
      identification than on White cultural competence and White cultural
      identification were found, and t-test comparisons revealed no gender differences
      on responses to the instruments. Analysis of variance was conducted to assess
      whether differences in perceived school environment could be attributed to
      cultural orientation. Rather than appearing assimilated, this generation of
      Lumbees tends to exhibit J. E. Helms's (1995b) Internalization identity status
      and an American Indian cultural orientation.

PMID- 15727498
TI  - Opioid craving and seeking behavior in physically dependent volunteers: effects
      of acute withdrawal and drug reinforcement opportunity.
AB  - This study examined whether acute opioid withdrawal and drug reinforcement
      opportunity increase opioid craving and seeking behavior. The author used a 3 x 2
      within-subject randomized crossover design to assess craving and operant
      behavioral effects of 3 pretreatments (naloxone 0.1 mg/70 kg, fentanyl 0.75 mg/70
      kg, or saline iv) and drug or money reinforcement opportunity in 8 methadone
      maintained volunteers. Each pretreatment was paired with response-contingent (15
      x fixed-ratio 100) delivery of drug (fentanyl 1.5 mg/70 kg iv) and money (rated
      equivalent of fentanyl) in different sessions. Naloxone significantly increased
      opioid craving, withdrawal signs, and symptoms, but not operant behavior,
      relative to saline and fentanyl pretreatment. However, drug versus money
      reinforcement opportunity did not significantly increase opioid craving or
      seeking behavior.

PMID- 15727499
TI  - Alcohol increases reliance on cues that signal acts of control.
AB  - This study examined the effects of alcohol on the ability to execute and inhibit
      behavior in a context in which preliminary information signaled the likelihood
      that a response should be executed or suppressed. Adults (N = 24) performed a
      cued go/no-go task that required quick responses to go targets and suppression of
      responses to no-go targets. Cue dependency was manipulated by varying the
      predictive validity of the cues, and performance was tested under 3 doses of
      alcohol: 0.00 g/kg, 0.45 g/kg, and 0.65 g/kg. Dose-dependent increases in cue
      dependence were only observed with highly predictive cues. Results suggest that
      alcohol-induced increases in stimulus control over behavior might be most likely
      in situations when stimulus control over behavior has already been established.

PMID- 15727501
TI  - Cognitive performance and autonomic reactivity in abstinent drug abusers and
      nonusers.
AB  - In this study the authors compared the performance of abstinent drug abusers (n =
      21) and nonuser control participants (n = 20) in neurocognitive and emotional
      functions by use of the Rogers Decision Making Task, Gambling Task, Emotional
      Stroop, impulsivity continuous performance task (CPT), and vigilance CPT. Skin
      conductance (SC) and heart rate (HR) monitoring was synchronized with task
      performance. Groups showed similar performance for vigilance, impulsivity, and
      emotional interference; however, drug abusers showed stronger SC responses. Drug
      abusers performed more poorly on the Gambling and Rogers Decision Making Tasks.
      When making risky decisions, drug abusers showed significantly less increase in
      SC activity than controls and exhibited lower HRs throughout performance on all
      tasks. In conclusion, complex tasks involving decision making, sensitivity to
      consequences, and emotional regulation discriminated between drug abusers and
      controls.

PMID- 15727502
TI  - Cash value of voucher reinforcers in pregnant drug-dependent women.
AB  - This study examined the relative reinforcing potency of vouchers and cash in drug
      dependent pregnant women (N = 48) across voucher values (US 10 dollars, US 50
      dollars, and US 100 dollars) by use of a series of choices to understand how
      exchange-delay features of voucher reinforcers influence their reinforcing
      potency compared with cash. The study also examined a no delay vs. 2-day delay of
      the cash alternative. Generally, cash was selected at 80%-90% of voucher face
      values. Vouchers were also discounted less when a 2-day delay was imposed on the
      cash option compared to the immediately available cash. These results suggest
      that voucher discounting does occur among patients in drug treatment. However,
      vouchers retain 80%-90% of their cash value and thus remain relatively potent
      reinforcers.

PMID- 15727503
TI  - Alcohol, intentional control, and inappropriate behavior: regulation by caffeine
      or an incentive.
AB  - This study shows that reduced intentional control under alcohol can be
      counteracted by caffeine or an environmental incentive. Four groups of social
      drinkers (n = 11) received 1 of the following: 0.62 g/kg alcohol (A), alcohol
      with 4.4 mg/kg caffeine (AC), alcohol with a rewarding monetary incentive (AR),
      or a placebo (P). They then performed a word stem completion task that provided
      separate measures of the influence of controlled and automatic processes
      governing responses. Controlled processes were depressed in Group A compared with
      Group P, whereas Groups AR and AC did not differ from Group P. Most inappropriate
      responses were displayed under alcohol alone, fewer with caffeine, and least with
      incentive. No treatment significantly affected automatic processes.

PMID- 15727504
TI  - Discriminative stimulus and self-reported effects of methylphenidate, d
      amphetamine, and triazolam in methylphenidate-trained humans.
AB  - Asymmetrical generalization between drugs on drug-discrimination procedures has
      been demonstrated for sedative and stimulant drugs in animals and to some extent
      with sedative drugs in humans. The aim of this experiment was to examine the
      discriminative-stimulus effects of d-amphetamine in methylphenidate-trained
      humans. A previous study demonstrated that methylphenidate substitutes for d
      amphetamine in d-amphetamine-trained humans. Six healthy human participants first
      learned to discriminate 30 mg oral methylphenidate. Doses of oral
      methylphenidate, d-amphetamine, triazolam, and placebo were then tested to
      determine whether they share discriminative-stimulus and self-reported effects
      with 30 mg methylphenidate. Methylphenidate and d-amphetamine dose-dependently
      increased methylphenidate-appropriate responding and produced prototypical
      stimulant-like effects. Triazolam produced low levels of methylphenidate
      appropriate responding and prototypical sedative-like effects. The results of
      this experiment are concordant with previous studies and suggest that the
      behavioral effects of oral methylphenidate and d-amphetamine overlap extensively
      and that the discriminative-stimulus effects of methylphenidate and d-amphetamine
      are symmetrical.

PMID- 15727505
TI  - Cue patterns and alcohol expectancies: how slight differences in stimuli can
      measurably change cognition.
AB  - Expectancy theory states that environmental cues provide the information
      necessary for organisms to predict what is upcoming in the world. Because this
      information is vast, mechanisms of simplification such as identification of cue
      patterns are thought to be necessary. This study tested the influence of 2
      different cue patterns on alcohol-related cognition. By simply changing the 1st
      word (milk vs. beer) on a study list comprising alcohol expectancy and grocery
      words, content differences in recalled words were demonstrated. Additionally,
      differences were a product of experience with alcohol. Findings were consistent
      with what would be predicted by cognitive concepts such as hybrid cuing and point
      to the need to take context and individual experience into account when studying
      memory processes.

PMID- 15727506
TI  - A comparison of anticonvulsants in the treatment of impulsive aggression.
AB  - This study compared the behavioral effects of 3 anticonvulsants in impulsive
      aggressive men. In a double-blind, placebo-controlled, parallel groups design,
      participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n =
      7), carbamazepine (n = 7), valproate (n = 7), or placebo (n = 8). The efficacy
      measure was the average aggression score, a global severity index from the Overt
      Aggression Scale (J. M. Silver & S. C. Yudofsky, 1991). Analysis showed a
      significant reduction in impulsive aggression during all 3 anticonvulsant
      conditions compared with placebo. However, the treatment effect during
      carbamazepine administration was slightly delayed compared with phenytoin and
      valproate. These findings suggest that increased use of anticonvulsants could
      make a significant impact in the control of impulsive aggression in both mental
      health and criminal justice settings.

PMID- 15727507
TI  - Distinguishing whether dopamine regulates liking, wanting, and/or learning about
      rewards.
AB  - To determine whether dopamine regulates liking, wanting, and/or learning about
      rewards during goal-directed behavior, the authors tested genetically engineered
      dopamine-deficient (DD) mice for acquisition of an appetitive T-maze task with
      and without endogenous dopamine signaling. Experiment 1 established that DD mice
      treated with L-dihydroxyphenylalanine (L-dopa [LD]) perform similarly to controls
      on a T-maze task designed to measure liking, wanting, and learning about rewards.
      Experiment 2, which tested saline-, caffeine-, and LD-treated DD mice on the T
      maze, separated performance factors from cognitive processes and revealed that
      dopamine is not necessary for mice to like or learn about rewards but is
      necessary for mice to seek (want) rewards during goal-directed behavior.

PMID- 15727508
TI  - Two types of aggression are differentially related to serotonergic activity and
      the A779C TPH polymorphism.
AB  - The authors investigated whether different types of aggression relate to the
      A779C tryptophan hydroxylase (TPH) polymorphism and to serotonergic activity in
      volunteers. A factor analysis of the Buss-Durkee Hostility Inventory yielded 2
      factors representing Neurotic Hostility (NH) and Aggressive Hostility (AH). The
      authors used a neuroendocrine challenge with Citalopram in 48 volunteers and
      increased cortisol concentrations only in those with high levels of AH. Finally,
      an association study with 58 volunteers revealed that the A779C TPH polymorphism
      significantly relates to AH, with the highest aggression levels for the genotype
      AA and the lowest aggression levels for the genotype CC, but not to NH. Results
      are discussed with respect to inconsistent findings in the literature, which may
      be explained by this distinction of types of aggression.

PMID- 15727510
TI  - Modulation of nicotine but not ethanol preference by the mouse Chrna4 A529T
      polymorphism.
AB  - Available evidence indicates that common genes influence alcohol and tobacco
      abuse in humans. The studies reported here used mouse models to evaluate the
      hypothesis that genetically determined variability in the alpha4beta2* nicotinic
      receptor modulates genetically determined variability in the intake of both
      nicotine and alcohol. Data obtained with inbred mouse strains suggested an
      association between a polymorphism in the mouse alpha4 nAChR subunit gene,
      Chrna4, and variability in nicotine and ethanol preference. These associations
      were assessed in F2 animals derived by crossing C57BL/6-super(beta2-/-) mice and
      A/J mice. The results obtained by the authors indicate that the polymorphism in
      Chrna4 plays an important role in modulating variability in oral nicotine intake
      but is linked to a gene that regulates alcohol intake.

PMID- 15727511
TI  - Impaired fear memories are correlated with subregion-specific deficits in
      hippocampal and amygdalar LTP.
AB  - Inbred mouse strains have different genetic backgrounds that likely influence
      memory and long-term potentiation (LTP). LTP, a form of synaptic plasticity, is a
      candidate cellular mechanism for some forms of learning and memory. Strains with
      impaired fear memory may have selective LTP deficits in different hippocampal
      subregions or in the amygdala. The authors assessed fear memory in 4 inbred
      strains: C57BL/6NCrlBR (B6), 129S1/SvImJ (129), C3H/HeJ (C3H), and DBA/2J (D2).
      The authors also measured LTP in the hippocampal Schaeffer collateral (SC) and
      medial perforant pathways (MPP) and in the basolateral amygdala. Contextual and
      cued fear memory, and SC and amygdalar LTP, were intact in B6 and 129, but all
      were impaired in C3H and D2. MPP LTP was similar in all 4 strains. Thus, SC, but
      not MPP, LTP correlates with hippocampus-dependent contextual memory expression,
      and amygdalar LTP correlates with amygdala-dependent cued memory expression, in
      these inbred strains.

PMID- 15727512
TI  - Dissociation of temporal dynamics of heart rate and blood pressure responses
      elicited by conditioned fear but not acoustic startle.
AB  - Fear-inducing stimuli were hypothesized to elicit fast heart rate (HR) responses
      but slow mean arterial blood pressure (MAP) responses and thus were studied in
      auditory fear conditioning and acoustic startle at high temporal resolution in
      freely moving mice and rats. Fear-induced instantaneous acceleration of HR
      reaching maximum physiological values and subsequent recovery to baseline were
      observed. The MAP response consisted of an immediate, mild, and transient
      increase followed by a sluggish, profound elevation and slow recovery. HR and MAP
      responses served as reliable indicators of conditioned fear in mice with
      dissociated temporal dynamics. Unconditioned auditory stimuli, including acoustic
      startle stimuli, elicited only fast, mild, and transient MAP and HR elevations in
      mice and rats, reflecting arousal and attention under these experimental
      conditions.

PMID- 15727513
TI  - Differences in prepulse inhibition (PPI) between Wistar and Sprague-Dawley rats
      clarified by a new method of PPI standardization.
AB  - Rat strain differences in the acoustic startle response (ASR) and prepulse
      inhibition (PPI) of that response are of increasing interest, especially as the
      genetics of PPI may provide an approach to studying the genetics of certain
      mental illnesses. However, strain differences in PPI are confounded by
      differences in ASR. To clarify this issue, the authors investigated the ASR and
      PPI across a range of startling stimulus intensities (70 dB-120 dB) in Wistar and
      Sprague-Dawley rats (N=96). Sprague-Dawleys showed more PPI of ASR capacity
      (response limit) than Wistars. In contrast, Wistars exhibited greater PPI than
      Sprague-Dawleys, as measured by an increase in response threshold. This
      dissociation suggests that PPI is more complex than that assessed by single
      startling stimulus intensity.

PMID- 15727515
TI  - Emotional response in patients with frontal brain damage: effects of affective
      valence and information content.
AB  - The authors investigated the role of the frontal lobes in the emotional response
      in 19 patients with brain damage and 23 control subjects. They studied the
      modulation of the startle blink reflex by affective pictures, and other autonomic
      responses. Patients showed a dissociation between the startle reflex and the
      affective valence ratings of the pictures, as a result of a low inhibition of the
      startle reflex by pleasant pictures. Pictures elicited lower skin conductance
      responses (SCRs) in patients than in controls, whereas the groups did not differ
      in the SCRs prompted by less significant acoustic stimuli. The findings point to
      the frontal lobe as a structure involved in the emotional response and in the
      physiological emotional arousal related to the complexity of the stimuli.

PMID- 15727514
TI  - Acquisition of differential delay eyeblink classical conditioning is independent
      of awareness.
AB  - There has been debate about whether differential delay eyeblink conditioning can
      be acquired without awareness of the stimulus contingencies. In 4 experiments,
      the authors reexamined this question. Older participants were tested with a tone
      and white noise (Experiment 1) or with 2 tones (Experiment 2). In addition,
      younger participants were tested with 2 tones (Experiment 3) or with 2 tones plus
      the parameters from an earlier study that had reported a relationship between
      conditioning and awareness (Experiment 4). Participants who were designated aware
      of the stimulus contingencies and participants who were designated unaware
      exhibited equivalent levels of differential eyeblink conditioning. Awareness of
      stimulus contingencies is not required for differential delay eyeblink
      conditioning when simple conditioned stimuli are used.

PMID- 15727516
TI  - Cortisol-induced impairments of working memory require acute sympathetic
      activation.
AB  - The present study assessed whether the effects of cortisol on working memory
      depend on the level of adrenergic activity (as measured by sympathetic
      activation) during memory performance. After exposure to a psychosocial stress
      task, participants were divided into cortisol responders and nonresponders.
      Cortisol responders showed working memory impairments during the psychosocial
      stress phase, when cortisol and adrenergic activity were enhanced, whereas
      nonresponders did not. During recovery, however, when cortisol levels were
      elevated but adrenergic activity was normalized, working memory of responders did
      not differ from that of nonresponders. Among several stress measures, cortisol
      was the only significant predictor for working memory performance during stress.
      These findings suggest that adrenergic activation is essential for the impairing
      effects of stress-induced cortisol on working memory.

PMID- 15727517
TI  - Sex differences and individual differences in cognitive performance and their
      relationship to endogenous gonadal hormones and gonadotropins.
AB  - Sexually dimorphic cognitive performance in men (n=42) and women (n=42) was
      related to testosterone, estradiol, progesterone, luteinizing hormone, follicle
      stimulating hormone, and sex hormone binding globulin, measured in 10-ml blood
      samples collected between 0900 and 1030 and, among women, during the follicular
      phase of the menstrual cycle. Significant sex differences favored men on spatial
      tasks (Mental Rotation and Judgment of Line Orientation) and on an inhibition
      task and favored women on a verbal task (category fluency). However, there were
      no significant relationships between any of the hormones and cognitive
      performance, suggesting that there are few, if any, consistent, substantial
      relationships between endogenous, nonfluctuating levels of gonadal hormones or
      gonadotropins and these cognitive abilities in men or women.

PMID- 15727518
TI  - Sex, age, and training modulate spatial memory in the rhesus monkey (Macaca
      mulatta).
AB  - The authors tested 90 rhesus monkeys (Macaca mulatta) on a task of spatial
      memory, the spatial Delayed Recognition Span Test. The results showed that
      performance declined significantly with age, males had greater scores than
      females, and the rate of apparent decline with age was greater in males than in
      females. Both working and reference memory declined with age, but only working
      memory showed sex differences. The authors compared these data with that of 22
      monkeys who were trained on a simpler version of the task before formal testing.
      Training had no effect on males but dramatically improved working memory in young
      females. The results confirm a male advantage in spatial working memory at a
      young age and confirm a greater decline with age in males than in females. It is
      important to note that prior training completely reverses the deficits of young
      females.

PMID- 15727519
TI  - Aged and adult rats compared in acquisition and extinction of escape from the
      water maze: focus on individual differences.
AB  - Individual differences in water maze and open-field performance of aged and adult
      rats were compared in a cross-sectional study. Three- and 24-month-old rats were
      classified into superior, moderate, and inferior groups on the basis of escape
      latencies during hidden platform acquisition and were compared regarding water
      maze acquisition and extinction, and open-field behavior. Unexpectedly, subgroup
      differences were invariant across age: The inferior and superior maze learners
      differed in (a) thigmotactic swimming during water maze acquisition and
      extinction and (b) open-field rearings. Thus, although aging has a detrimental
      effect on water maze acquisition and extinction, the degree of impairment might
      be partly determined by individual novelty-induced rearing activity and
      thigmotactic swimming at adult ages.

PMID- 15727520
TI  - The role of hippocampal subregions in detecting spatial novelty.
AB  - Previous literature suggests that the hippocampus subserves processes associated
      with the encoding of novel information. To investigate the role of different
      subregions of the hippocampus, the authors made neurotoxic lesions in different
      subregions of the dorsal hippocampus (i.e., CA1, dentate gyrus [DG], or CA3) of
      rats, followed by tests using a spontaneous object exploration paradigm. All
      lesion groups explored normally an object newly introduced in a familiar
      location. However, when some of the familiar objects were moved to novel
      locations, both DG and CA3 lesion groups were severely impaired in reexploring
      the displaced objects, whereas the CA1 lesion group was only mildly impaired in
      reexploration. The results suggest that the DG-CA3 network is essential in
      detecting novelty for spatial, but not for individual object, information.

PMID- 15727521
TI  - The ventral hippocampus supports a memory representation of context and
      contextual fear conditioning: implications for a unitary function of the
      hippocampus.
AB  - The authors report that either inactivating the ventral hippocampus (VH) with
      muscimol prior to context preexposure or injecting anisomycin into the VH after
      preexposure significantly impaired rats' memory for context. Injecting anisomycin
      into the VH prior to contextual fear conditioning also greatly reduced long-term
      memory (48-hr retention test) but had no effect on short-term memory (1-hr
      retention test) for contextual fear. Together with other results, these data
      suggest that the memory for a novel context is distributed throughout the
      longitudinal extent of the hippocampus and that this representation helps to
      support contextual fear conditioning.

PMID- 15727522
TI  - Single neurons in the dentate gyrus and CA1 of the hippocampus exhibit inverse
      patterns of encoding during trace fear conditioning.
AB  - Trace fear conditioning is a hippocampus-dependent learning task that requires
      the association of an auditory conditioned stimulus (CS) and a shock
      unconditioned stimulus (US) that are separated by a 20-s trace interval. Single
      neuron activity was recorded simultaneously from the dentate gyrus (DG) and CA1
      of rats during unpaired pseudoconditioning and subsequent trace fear
      conditioning. Single neurons in DG showed a progressive increase in learning
      related activity to the CS and US across trace fear conditioning. Single neurons
      in CA1 showed an early increase in responding to the CS, which developed into a
      decrease in firing later in trace conditioning. Correlation analyses showed that
      DG and CA1 units exhibit inverse patterns of responding to the CS during trace
      fear conditioning.

PMID- 15727523
TI  - Medial prefrontal lesions and Pavlovian eyeblink and heart rate conditioning:
      effects of partial reinforcement on delay and trace conditioning in rabbits
      (Oryctolagus cuniculus).
AB  - Effects of continuous (100%) versus partial (25%) reinforcement were studied on
      Pavlovian delay and trace eyeblink conditioning in rabbits (Oryctolagus
      cuniculus) with either lesions to the medial prefrontal cortex (mPFC) or sham
      lesions. Concomitant heart rate changes evoked by the conditioned stimulus were
      also assessed. Partial reinforcement retarded eyeblink conditioning in both the
      trace and delay paradigm, but this impairment was greater during trace
      conditioning and in rabbits with mPFC lesions. Accompanying conditioned stimulus
      evoked heart rate slowing was attenuated under all conditions by the mPFC
      lesions, although this result was not always statistically significant.

PMID- 15727524
TI  - Purkinje cell loss by OX7-saporin impairs excitatory and inhibitory eyeblink
      conditioning.
AB  - Cerebellar cortical contributions to eyeblink conditioned excitation have been
      examined extensively. In contrast, very little evidence exists concerning the
      role of the cerebellar cortex in eyeblink conditioned inhibition. In the current
      study, rats were given intraventricular infusions of the immunotoxin OX7-saporin
      to selectively destroy Purkinje cells throughout the cerebellar cortex following
      excitatory conditioning. After a 2-week postinfusion period, the rats were given
      reacquisition training. After reacquiring excitatory conditioning, the rats were
      trained in a feature-negative discrimination procedure to establish conditioned
      inhibition. Rats treated with OX7-saporin showed impaired reacquisition of
      excitatory conditioning and acquisition of conditioned inhibition. The results
      suggest that Purkinje cells play important, but different, roles in conditioned
      excitation and inhibition in rats.

PMID- 15727525
TI  - Amygdala central nucleus function is necessary for learning, but not expression,
      of conditioned auditory orienting.
AB  - In Pavlovian appetitive conditioning, rats often acquire 2 classes of conditioned
      responses: those whose form is determined by the reinforcer, and those whose form
      is determined by characteristics of the conditioned stimulus (CS). Consistent
      with the results of previous lesion studies, reversible inactivation of amygdala
      central nucleus function during pairings of an auditory CS with food prevented
      the acquisition of conditioned orienting responses specific to auditory CSs,
      whereas food-related conditioned behaviors were acquired normally. Neither
      inactivation nor posttraining neurotoxic lesions of the central nucleus affected
      the expression of previously acquired conditioned orienting. Thus, although the
      central nucleus is critical to the acquisition of information required for
      conditioned orienting to auditory cues, it is not needed for maintaining this
      information for later use.

PMID- 15727526
TI  - Ethanol-induced conditioned place preference is expressed through a ventral
      tegmental area dependent mechanism.
AB  - The authors examined the role of the ventral tegmental area (VTA) and nucleus
      accumbens (NAc) in the expression of ethanol-induced conditioned place preference
      (CPP). After cannulas were implanted, male DBA/2J mice underwent an unbiased
      Pavlovian-conditioning procedure for ethanol-induced CPP. Before preference
      testing, the mice were injected intra-VTA (Experiments 1 and 3) or intra-NAc
      (Experiment 2) with the nonselective opioid antagonist methylnaloxonium (0-ng,
      375-ng, or 750-ng total infusion; Experiments 1 and 2) or the gamma aminobutyric
      acid (GABA(B)) agonist baclofen (0-ng, 25-ng, or 50-ng total infusion; Experiment
      3). Intra-VTA methylnaloxonium or baclofen decreased ethanol-induced CPP, whereas
      intra-NAc methylnaloxonium had no effect. These findings indicate that the
      conditioned rewarding effect of ethanol is expressed through a VTA-dependent
      mechanism that involves both opioid and GABA(B) receptors.

PMID- 15727527
TI  - 6-Hydroxydopamine lesions in female hamsters (Mesocricetus auratus) abolish the
      sensitized effects of sexual experience on copulatory interactions with males.
AB  - This study examined the effects of sexual experience in female hamsters
      (Mesocricetus auratus) on copulatory interactions with male hamsters. Female
      sexual experience improved the copulatory efficiency of sexually naive males, an
      effect that persisted for at least 6 weeks without further sexual behavior
      testing. In a 2nd study, dopamine lesions made in the region of the nucleus
      accumbens prior to sexual experience specifically blocked the effects of the
      female's sexual experience on the hit rate of naive males. These results suggest
      that sexual experience in female hamsters increases the efficiency of copulatory
      interactions with males, that these effects persist in the absence of further
      sexual experience, and that dopamine neurotransmission in the basal forebrain
      underlies this effect of sexual experience.

PMID- 15727528
TI  - Social suppression of song is associated with a reduction in volume of a song
      control nucleus in European starlings (Sturnus vulgaris).
AB  - In seasonally breeding songbirds, variations in testosterone and song correlate
      with volume changes in brain nuclei associated with song, including the HVC. The
      authors tested whether singing can lead to activity-dependent increases in HVC
      volume by examining song output in starlings (Sturnus vulgaris). The authors
      manipulated males' environments so that only some were dominant with nestboxes,
      whereas others were not. Some of these males thus sang at higher rates and had
      larger HVC volume than others. The study was conducted over 2 years. In 1 year,
      males selectively occupied nestboxes but did not sing. HVC volume did not differ
      in these starlings, indicating that nestbox possession alone cannot increase HVC.
      The findings suggest that changes in song nuclei volume can be driven by changes
      in singing.

PMID- 15727530
TI  - Cortical responses in rats predict perceptual sensitivities to complex sounds.
AB  - The common assumption that perceptual sensitivities are related to neural
      representations of sensory stimuli has seldom been directly demonstrated. The
      authors analyzed the similarity of spike trains evoked by complex sounds in the
      rat auditory cortex and related cortical responses to performance in an auditory
      task. Rats initially learned to identify 2 highly different periodic, frequency
      modulated sounds and then were tested with increasingly similar sounds. Rats
      correctly classified most novel sounds; their accuracy was negatively correlated
      with acoustic similarity. Rats discriminated novel sounds with slower modulation
      more accurately than sounds with faster modulation. This asymmetry was consistent
      with similarities in cortical representations of the sounds, demonstrating that
      perceptual sensitivities to complex sounds can be predicted from the cortical
      responses they evoke.

PMID- 15727529
TI  - Evidence for opioid involvement in the regulation of song production in male
      European starlings (Sturnus vulgaris).
AB  - Many social animals vocalize at high rates, suggesting that vocal communication
      is highly motivated and rewarding. In songbirds, much is known about the neural
      control of vocal behavior; however, little is known about neurobiological
      mechanisms regulating the motivation to communicate. This study examined a
      possible role for opioid neuropeptides in motivation and reward associated with
      song production in male European starlings (Sturnus vulgaris). Peripheral opioid
      blockade facilitated male song production. Furthermore, methionine-enkephalin
      immunolabeled fiber densities within brain regions in which opioids are known to
      regulate motivation and reward (i.e., the medial preoptic nucleus and ventral
      tegmental area) related positively to male song production. These data suggest
      that song production might be regulated by opioid activity within motivation and
      reward neural systems.

PMID- 15727531
TI  - Psychophysical investigations of cetylpyridinium chloride in rats: its inherent
      taste and modifying effects on salt taste.
AB  - Salts are transduced by at least 2 mechanisms: (a) antagonized by amiloride and
      (b) antagonized by cetylpyridinium chloride (CPC). The authors report on 4
      behavioral experiments in rats that characterize the orosensory properties of CPC
      itself as well as its effect in suppressing the intensity of NaCl and KCl taste.
      Experiments 1 and 2 indicated that CPC has a quinine-like taste quality.
      Experiments 3 and 4 demonstrated that the recognition of KCl, but not NaCl, is
      modestly reduced by mixture with CPC. However, control experiments call into
      question the mechanism of the salt suppression of CPC, because both CPC-salt and
      quinine-salt mixtures had similar effects. The relevance of these studies for
      understanding salt and bitter taste coding is discussed.

PMID- 15727533
TI  - Neonatal infection induces memory impairments following an immune challenge in
      adulthood.
AB  - Exposure to infectious agents during early postnatal life often alters
      glucocorticoid responses to stress and immune outcomes in adulthood. The authors
      examined whether neonatal infection results in memory impairments in adult
      animals. Rats infected with Escherichia coli (E. coli) as neonates displayed
      impaired memory for a recently explored context in adulthood. This impairment,
      however, was only observed in rats that received a peripheral immune challenge
      (lipopolysaccharide; LPS) immediately following context exposure. Adult rats
      treated neonatally with E. coli also had decreased hippocampal astrocytes
      compared with phosphate-buffered saline-treated rats, but displayed increased
      astrocyte reactivity in the hippocampus and decreased brain interleukin-1beta
      following lipopolysaccharide. Infection during development appears to alter glia
      within the hippocampus, which may contribute to altered cytokine responses and
      memory impairment.

PMID- 15727532
TI  - Ferret odor as a processive stress model in rats: neurochemical, behavioral, and
      endocrine evidence.
AB  - Predator odors have been shown to elicit stress responses in rats. The present
      studies assessed the use of domestic ferret odor as a processive stress model.
      Plasma corticosterone and adrenocorticotropin hormone levels were higher after 30
      min of exposure to ferret odor (fur/skin) but not control odors, ferret feces,
      urine, or anal gland secretions. Behavioral differences were also found between
      ferret and the control odors as tested in a defensive withdrawal paradigm. In
      addition, c-fos messenger RNA expression in several brain areas previously
      associated with processive stress was significantly higher in ferret odor-exposed
      rat brains than in control odor-exposed brains. These results suggest that ferret
      odor produces a reliable unconditioned stress response and may be useful as a
      processive stress model.

PMID- 15727534
TI  - Prenatal alcohol exposure causes attention deficits in male rats.
AB  - Children with fetal alcohol spectrum disorder (FASD) are often diagnosed with
      attention-deficit/ hyperactivity disorder (ADHD). These children show increases
      in reaction time (RT) variability and false alarms on choice reaction time (CRT)
      tasks. In this study, adult rats prenatally exposed to ethanol were trained to
      perform a CRT task. An analysis of the distribution of RTs obtained from the CRT
      task found that rats with a history of prenatal ethanol exposure had more
      variable RT distributions, possibly because of lapses of attention. In addition,
      it was found that, similar to children with FASD, the ethanol-exposed rats had
      more false alarms. Thus, rats with prenatal ethanol exposure show attention
      deficits that are similar to those of children with FASD and ADHD.

PMID- 15727535
TI  - A specific sexual orientation-related difference in navigation strategy.
AB  - During spatial navigation, women typically navigate an environment using a
      landmark strategy, whereas men typically use an orientation strategy. To examine
      the as yet unknown effects of sexual orientation on these normative sex
      differences, this study required 80 healthy heterosexual and homosexual adult men
      and women to provide directions from experimental maps for 4 routes. The
      frequency and type of strategy used by each participant were computed. Expected
      sex differences were demonstrated, and a robust cross-sex shift was shown by
      homosexual men in using landmarks. This remained after controlling for
      differences in mental rotation, directional sense, and general intelligence. The
      findings may limit the number of putative neurodevelopmental pathways responsible
      for sex differences in navigation strategy utility.

PMID- 15727537
TI  - The mesocortical dopamine projection to anterior cingulate cortex plays no role
      in guiding effort-related decisions.
AB  - Both mesolimbic dopamine (DA) and the anterior cingulate cortex (ACC) have been
      implicated in enabling animals to expend effort to obtain greater reward. To
      investigate the role of the DA pathway to ACC in working for reward, the authors
      tested rats on a cost-benefit T-maze paradigm in which they could either climb a
      barrier to obtain large reward in 1 arm (high reward [HR]) or select the low
      effort alternative containing less reward (low reward [LR]). Surprisingly, ACC DA
      depletions had no effect on choice performance. Manipulations of barrier and
      reward sizes demonstrated that lesioned rats were as sensitive to the costs and
      benefits of the alternatives as controls. These results imply that the DA
      projection to ACC is not involved in guiding effort-related decisions.

PMID- 15727536
TI  - Orbitofrontal lesions impair use of cue-outcome associations in a devaluation
      task.
AB  - The orbitofrontal cortex (OFC) has been implicated in the use of outcome
      expectancies to guide behavior. The present study used a devaluation task to
      examine this function. Rats first received light-food pairings followed by food
      toxin pairings designed to devalue the food. After either excitotoxic or sham OFC
      lesions, responding to the light was reassessed. Sham-lesioned rats showed
      reduced responding to the light relative to behavioral controls, which had
      received food and toxin unpaired. In contrast, OFC-lesioned rats showed no such
      reductions. Combined with previous data (C. L. Pickens, M. P. Saddoris, B.
      Setlow, M. Gallagher, P. C. Holland, & G. Schoenbaum, 2003), these results
      indicate that the OFC is critical for the maintenance of information about the
      current incentive value of reinforcers or the use of that information to guide
      behavior.

PMID- 15727538
TI  - Olfactory-mediated fear conditioning in mice: simultaneous measurements of fear
      potentiated startle and freezing.
AB  - This study demonstrates that mice display olfactory-cued fear as measured with
      both freezing and fear-potentiated startle. Following a preconditioning test to
      measure any unconditioned responses to odor, mice received 5 pairings of a 10-s
      odor with a 0.25-s, 0.4-mA footshock. The next day, startle and freezing were
      measured in the presence and absence of the odor. Both fear measures increased
      after training with amyl acetate (Experiment 1) and acetophenone (Experiment 2).
      The enhancement of startle did not occur when the same number of odors and shocks
      were presented in an unpaired fashion (Experiment 3). Furthermore, mice were able
      to discriminate between an odor paired with shock and a nonreinforced odor
      (Experiment 4).

PMID- 15727539
TI  - Espresso reward learning, hold the dopamine: theoretical comment on Robinson et
      al. (2005).
AB  - QUESTION: Is dopamine needed for reward learning? ANSWER: No--at least, not in
      the brain of a caffeinated dopamine-deficient (DD) mutant mouse. That is the
      conclusion of an important paper in this issue by S. Robinson, S. M. Sandstrom,
      V. H. Denenberg, and R. D. Palmiter (see record 2005-01705-001). Those authors
      demonstrate that reward learning can proceed normally in the brains of DD mice,
      even though they contain no dopamine at the time of learning, if the mice are
      given caffeine just before learning. Caffeine activates the DD mice by a
      nondopaminergic mechanism, allowing them to learn where to obtain food reward in
      a T-maze runway. Their reward-learning-without-dopamine is revealed on a
      subsequent test day, when dopamine function is restored by L-dopa administration.
      Robinson et al. conclude that dopamine is not needed for normal learning about
      rewards, or for hedonic "liking" of rewards during learning, but rather
      specifically for a motivational "wanting" component of reward, such as incentive
      salience.

PMID- 15727540
TI  - The role of hippocampal regions CA3 and CA1 in matching entorhinal input with
      retrieval of associations between objects and context: theoretical comment on Lee
      et al. (2005).
AB  - Models of hippocampal function have proposed different functions for hippocampal
      regions CA3 and CA1, commonly proposing that CA1 performs a match-mismatch
      comparison of memory retrieval with sensory input. The study by I. Lee, M. R.
      Hunsaker, and R. P. Kesner (2005) tested these models using selective lesions of
      hippocampal subregions (see record 2005-01705-014). Their data suggest that CA3
      and the dentate gyrus play an important role in the process of detecting the
      mismatch when a familiar object is placed in a new spatial location. Lesions of
      the dentate gyrus and CA3 strongly reduce the enhanced exploration associated
      with displaced objects, beyond the reduction caused by CA1 lesions. This supports
      the importance of convergent input to CA3 as well as CA1. Along with recent
      electrophysiological data, this provides a framework for more specifically
      modeling the role of CA3 and CA1 in matching sensory input with context-dependent
      retrieval for memory-guided behavior in different tasks.

PMID- 15727541
TI  - Activity dependent brain plasticity: does singing increase the volume of a song
      system nucleus? Theoretical comment on Sartor and Ball (2005).
AB  - The avian telencephalic song system, including nucleus high vocal center (HVC),
      is an important model for the study of brain plasticity. J. J. Sartor and G. F.
      Ball (2004) asked whether song activity itself could increase HVC volume (see
      record 2005-01705-022). They report that male starlings that sang more, motivated
      by gaining possession of a nest box in competition with another male, had larger
      HVCs than males that sang less. These results are suggestive but correlational. A
      more direct experimental approach will be required to establish that HVC size is
      activity dependent. Their experiment is an important first step, however. The
      song activity hypothesis merits continued investigation because of its potential
      to produce unique insights into naturally occurring brain plasticity.

PMID- 15727542
TI  - Living with schizophrenia: a family perspective.
AB  - The lifetime emotional, social, and financial consequences experienced by
      individuals with schizophrenia have significant effects on their families. Family
      responses to having a family member with schizophrenia include: care burden, fear
      and embarrassment about illness signs and symptoms, uncertainty about course of
      the disease, lack of social support, and stigma. Study findings about families in
      which parents are hostile, critical, or overly involved are equivocal about
      whether this negative environment contributes to patient relapse. This review
      summarizes the studies related to the family responses and emotional environment
      of families who have a member with schizophrenia.

PMID- 15727543
TI  - Securing your PC and protecting your privacy.
AB  - Working in a networked information environment brings new opportunities for
      getting and sharing information. Regrettably, these benefits of the Internet are
      challenged by forces that would interfere to satisfy their own profit or
      malevolent motives. Your networked computer can be infected by viruses, worms, or
      Trojan horses or infiltrated by spyware, adware, or pop-ups. Without being aware
      of the dangers and taking precautionary steps, your PC is susceptible to being
      compromised and your privacy invaded. This column will highlight some of the
      dangers and offer basic steps for securing your computer and protecting your
      privacy.

PMID- 15727544
TI  - Partnerships and collaboration: what skills are needed?

PMID- 15727545
TI  - Ten lessons in collaboration.
AB  - Collaboration is a substantive idea repeatedly discussed in health care circles.
      The benefits are well validated. Yet collaboration is seldom practiced. So what
      is the problem? The lack of a shared definition is one barrier. Additionally, the
      complexity of collaboration and the skills required to facilitate the process are
      formidable. Much of the literature on collaboration describes what it should look
      like as an outcome, but little is written describing how to approach the
      developmental process of collaboration. In an attempt to remedy the all too
      familiar riddle of matching ends with means, this article offers key lessons to
      bridge the discourse on collaboration with the practice of collaboration. These
      lessons can benefit clinical nurse managers and all nurses who operate in an
      organizational setting that requires complex problem solving.

PMID- 15727546
TI  - New horizons for collaborative partnershipss.
AB  - The need for partnerships between health care professionals within geographical
      communities is becoming increasingly important as new health care needs, trends,
      and issues are identified. Frequently, nurses are key stakeholders within these
      alliances or partnerships. This article identifies three essential elements
      associated with successful collaborative partnerships, namely networking,
      leadership, and vision. It shares examples of various collaborative efforts in
      which the authors have engaged, illustrating how networking, leadership, and
      vision have enhanced these collaborative efforts.

PMID- 15727547
TI  - Interprofessional relationships and collaborative working: encouraging reflective
      practice.
AB  - A challenge for those involved in the education and professional development of
      health and social care practitioners is to find ways of encouraging and enabling
      them to critically reflect upon complex collaborative situations and consider how
      they might improve interprofessional relationships. To meet this challenge, we
      piloted and developed a reflective exercise derived from methods used in personal
      construct psychology (Hargreaves,1979; Salmon,1994), which has proved to be
      useful in three overlapping areas; research, professional development, and
      classroom teaching. To illustrate the technique, this paper presents a case study
      of one district nurse who used the method to help her examine complex
      interprofessional relationships when providing long-term community care. The
      reflective technique (which uses arrow-shaped cards displayed on large visual
      layouts) was found to provide a rich description of the individual's
      relationships. By employing the visual displays the district nurse was able to
      explore the meanings of professional identity and roles in terms of professional
      relationships, and to consider her intentions and actions within a complex
      multidisciplinary situation.

PMID- 15727548
TI  - Nurse-physician workplace collaboration.
AB  - Maximizing nurse-physician collaboration holds promise for improving patient care
      and creating satisfying work roles. The purpose of this article is to describe
      strategies that will facilitate effective nurse-physician collaboration. First
      the nature and the benefits of collaborative communication will be reviewed. This
      review will be followed by a discussion of self-development, team-development,
      and communication-development strategies that can enhance nurse-physician
      collaboration.

PMID- 15727549
TI  - Collaboration: leadership in a global technological environment.
AB  - Although collaboration is not a new idea, new opportunities for collaboration
      exist in this 21st century global-knowledge and information-driven economy.
      Technology has reduced time and space while enhancing communication, thereby
      opening the possibilities of exploring new boundaries in the area of
      interdisciplinary collaboration. The goal of this article is to assist leaders in
      changing the language of organizations so that new technologies can enhance
      collaboration. A systematic approach for leaders to use in assisting assist
      persons, groups, and organizations in integrating new technologies into their
      organizations locally and globally is offered, along with a summary of new, and
      several established, collaboration techniques.

PMID- 15727551
TI  - The impact of nanobiotechnology on the development of new drug delivery systems.
AB  - Nanotechnology, or systems/devices manufactured at the molecular level, is a
      multidisciplinary scientific field undergoing explosive development. A part of
      this field is the development of nanoscaled drug delivery devices. Nanoparticles
      have been developed as an important strategy to deliver conventional drugs,
      recombinant proteins, vaccines and more recently nucleotides. Nanoparticles and
      other colloidal drug delivery systems modify the kinetics, body distribution and
      drug release of an associated drug. Other effects are tissue or cell specific
      targeting of drugs and the reduction of unwanted side effects by a controlled
      release. Therefore nanoparticles in the pharmaceutical biotechnology sector
      improve the therapeutic index and provide solutions for future delivery problems
      for new classes of so called biotech drugs including recombinant proteins and
      oligonucleotides. This review discusses nanoparticular drug carrier systems with
      the exception of liposomes used today, and what the potential and limitations of
      nanoparticles in the field of pharmaceutical biotechnology are.

PMID- 15727552
TI  - Intraocular delivery of oligonucleotides.
AB  - Anti-mRNA and particularly antisense oligonucleotides are molecules able to
      inhibit gene expression after intracellular penetration being potentially very
      interesting for the treatment of ocular diseases where growth factors are
      involved such as ocular scarring diseases or for the inhibition of viral
      multiplication. In most cases, the site of action of oligonucleotides has shown
      to be the posterior segment of the eye and these molecules are injected mainly by
      the intravitreal route. However, oligonucleotides are poorly stable in biological
      fluids, have a low intracellular penetration and are quickly eliminated form the
      vitreous. These issues request repeated administration of oligonucleotides which
      are able to induce severe damages to the retina. This is the reason why drug
      delivery systems were developed to improve the stability and intracellular
      penetration of oligonucleotides and, by sustained release, to increase their long
      term activity in the treatment of ocular diseases.

PMID- 15727553
TI  - Nanotechnology on duty in medical applications.
AB  - At the beginning of 21(st) century, fifty years after discovery of
      deoxyribonucleic acid (DNA) double helix structure, scientific world is faced
      with a great progress in many disciplines of biological research, especially in
      the field of molecular biology and operating on nucleid acid molecules. Many
      molecular biology techniques have been implemented successfully in biology,
      biotechnology, medical science, diagnostics, and many more. The introduction of
      polymerase chain reaction (PCR) resulted in improving old and designing new
      laboratory devices for PCR amplification and analysis of amplified DNA fragments.
      In parallel to these efforts, the nature of DNA molecules and their construction
      have attracted many researchers. In addition, some studies concerning mimicking
      living systems, as well as developing and constructing artificial nanodevices,
      such as biomolecular sensors and artificial cells, have been conducted. This
      review is focused on the potential of nanotechnology in health care and medicine,
      including the development of nanoparticles for diagnostic and screening purposes,
      the manufacture of unique drug delivery systems, antisense and gene therapy
      applications and the enablement of tissue engineering, including the future of
      nanorobot construction.

PMID- 15727554
TI  - Smart nanotubes for biotechnology.
AB  - Nanotechnology concerns the science of very small particles and deals with both
      the fundamental aspects of understanding the properties of such nanoparticles and
      with developing technological applications of nanoparticles. Biomedical and
      biotechnological applications of nanoparticles have been of special recent
      research and development interest, with potential applications that include use
      of nanoparticles as drug (or DNA) delivery vehicles, and as components in medical
      diagnostic kits, biosensors and membranes for bioseparations. Spherical
      nanoparticles are typically used for such applications, but this only reflects
      the fact that spheres are easier to make than nanoparticles having other shapes.
      Micro and nanotubes - structures that resemble tiny drinking straws - are
      alternatives and may offer advantages over spherical nanoparticles for some
      applications. This article discusses different approaches for making micro and
      nanotubes and reviews the current status of efforts to develop biomedical and
      biotechnological applications of these tubular structures.

PMID- 15727555
TI  - Recombinant virus like particles as drug delivery system.
AB  - The drug delivery system described here is based on a virus like particle
      consisting of the recombinant expressed major capsid protein of Polyomavirus,
      VP1. Polyoma, a murine virus belonging to the Papovaviridae, forms a non
      enveloped icosahedral capsid. These capsids are organized as a double shell
      composed of three different proteins: VP1,VP2 and VP3. The outer shell of the
      vision is composed of 360 VP1 molecules arranged as 72 pentamers. These capsids
      have a diameter of about 50 nm. The VP1 protein acts as a major ligand for
      certain membrane receptors during virus infection. Furthermore, the N-terminus of
      the VP1 protein contains a DNA-binding domain and a nuclear localization
      sequence. The recombinant production of the VP1 protein offers a save way to
      obtain a highly purified, non pathogenic pharmaceutical excipient. Combining
      these aspects, VP1 proteins provide a targeting as well as a drug binding site
      when used as a save drug carrier for gene therapy. Current applications are also
      including oligonucleotides as well as small molecules as well as vaccines.

PMID- 15727556
TI  - An integrated platform for bio-analysis and drug delivery.
AB  - The advances in the microelectronics fabrication allow the strong appearance of
      micro-electro-mechanical systems known as MEMS. MEMS enable the fabrication of
      smaller devices that are manufactured using standard micro-fabrication techniques
      similar to the ones that are used to create computer silicon chips. Several MEMS
      devices including micro-reservoirs, micro-pumps, cantilevers, rotors, channels,
      valves, sensors, and other structures have been designed, fabricated and tested
      from using materials that have been demonstrated to be biocompatible. This paper
      reviews the status of Micro-electronic and MEMS systems that can be used for
      adaptive drug administration. It presents different components and describes a
      possible implementation. Finally it presents a prototype that is termed ipill
      which stands intelligent pill.

PMID- 15727557
TI  - Effects of erythropoietin on brain function.
AB  - This article is a selective extension of a review on recombinant human
      erythropoietin (rHu-EPO) as an anti-anaemic drug, published in this journal in
      2000. It summarises the recent advances in understanding the molecular mechanisms
      by which the hypoxia-inducible transcription factor 1 (HIF-1) regulates O(2)
      dependent genes, including the EPO gene in brain. With respect to brain
      integrity, EPO exerts positive effects in two different ways. First, rHu-EPO
      raises the blood haemoglobin concentration and, hence, the O(2) capacity of the
      blood in anaemic patients. The restored O(2) supply ameliorates attention
      difficulties and psychomotor slowing, improves memory capacities and normalises
      neuroendocrine functions. Second, EPO can act as a neurotrophic and
      neuroprotective factor directly in brain. EPO and its receptor are expressed in
      the cerebral cortex, cerebellum, hippocampus, pituitary gland and spinal cord. In
      vitro EPO protects against glutamate-induced cell death in a dose-dependent way.
      In animal models it reduces volumes of brain ischaemia, protects the cortex from
      hypoxic damage and leads to survival of neurons and synapses. One can expect that
      in the near future rHu-EPO will be used therapeutically in cerebral ischaemia,
      brain trauma, inflammatory diseases, and neural degenerative disorders. A first
      clinical trial has shown the neuroprotective effectiveness of the drug in
      cerebral ischaemia.

PMID- 15727558
TI  - Application of sterylglucoside-containing particles for drug delivery.
AB  - Recent advances in biotechnology have promoted biomolecular targeting of drugs,
      peptides and genes in the treatment and management of major diseases and
      infections. Therapeutic development of drugs and delivery systems may have
      various objectives: Systemic drugs require optimal delivery and uptake at target
      sites; peptide drugs require alternative routes of administration, such as nasal
      or intestinal absorption; gene medicines need to be delivered efficiently, safely
      and selectively to diseased areas. The propensity of ligand-modified liposomes to
      carry drugs and genes to desirable sites has been extensively examined and
      current reports show considerable progress in this field. Sterylglucoside (SG) is
      a novel absorption-enhancer of peptide drugs across nasal and intestinal mucosae.
      Physico-chemical properties and biodistribution of liposomes incorporating SG
      were studied and compared against the profiles of aglycon and sitosterol
      derivatives of SG. It was shown that SG particles aided colon drug delivery and
      increased bioavailability of peptide drugs after nasal and intestinal
      administration. In addition, they were able to enhance anticancer effects in
      liver cancer chemotherapy. Biological fate and interaction of SG with hepatocytes
      support the novel proposition of liver-targeting SG-liposomes.

PMID- 15727560
TI  - Demonstration and characterization of phosphate transport in mammalian
      peroxisomes.
AB  - It is now well established that the peroxisomal membrane is not freely permeable
      to small molecules in vivo, which implies the existence of metabolite
      transporters in the peroxisomal membrane. A few putative peroxisomal metabolite
      transporters have indeed been identified, but the function of these proteins has
      remained largely unresolved so far. The only peroxisomal transporter
      characterized to a significant extent is the adenine nucleotide transporter,
      which is presumably required to sustain the activity of the intraperoxisomal very
      long-chain-acyl-CoA synthetase. In addition to AMP, this acyl-CoA synthetase also
      produces pyrophosphate, which must be exported from the peroxisome. In the
      present study, we demonstrate that the peroxisomal membrane contains a
      transporter activity that facilitates the passage of phosphate and possibly
      pyrophosphate across the peroxisomal membrane. By reconstitution of peroxisomal
      membrane proteins in proteoliposomes, some kinetic parameters of the transporter
      could be established in vitro. The transporter can be distinguished from the
      mitochondrial phosphate transporter by its different sensitivity to inhibitors.

PMID- 15727563
TI  - Double mutant of Aspergillus oryzae for improved production of L-dopa (3,4
      dihydroxyphenyl-L-alanine) from L-tyrosine.
AB  - Aspergillus oryzae mutant strain UV-7 was further improved for the production of
      L-dopa from L-tyrosine using chemical mutation. Different putative mutant strains
      of the organism were tested for the production of L-dopa in triplicate shake
      flask cultures. Among these putative mutants, the strain designated SI-12 gave a
      maximal production of L-dopa (444+/-14 mg of L-dopa/g of cells). The regulation
      of L-dopa from different carbon source solutions [initial substrate concentration
      (S(0))=30 g/l] by the mutant culture was investigated. At an initial pH (pH(0))
      of 5.0 and a temperature (T) of 30 degrees C, 100% of sugars were utilized for
      product and cell mass formation, corresponding to final L-dopa product yield of
      189+/-8 mg/g of substrate utilized and maximum volumetric and specific
      productivities of 145+/-5 mg/h per litre and 155+/-8 mg/h per g of cells
      respectively. There was up to 3-fold enhancement in product formation rate. This
      enhancement is, to our knowledge, the highest reported in the literature. To
      explain the kinetic mechanism of L-dopa formation and its thermal inactivation,
      the thermodynamic parameters were determined with the application of the
      Arrhenius model. Activation enthalpy and entropy for product formation, in the
      case of the mutant derivative, were 40 kJ/mol and 0.076 kJ.mol(-1).K(-1) for its
      production and 116 kJ/mol and 0.590 kJ.mol(-1).K(-1) for thermal inactivation
      respectively. The respective values for product formation and product de
      activation were lower than the respective values for the parental culture.
      Therefore the mutant strain was thermodynamically more resistant to thermal
      denaturation during the product-formation process.

PMID- 15727561
TI  - Molecular and biochemical characterization of an endo-beta-1,3-glucanase from the
      pinewood nematode Bursaphelenchus xylophilus acquired by horizontal gene transfer
      from bacteria.
AB  - We report the cloning and functional characterization of an endo-beta-1,3
      glucanase from the pinewood nematode Bursaphelenchus xylophilus acquired by
      horizontal gene transfer from bacteria. This is the first gene of this type from
      any nematode species. We show that a similar cDNA is also present in another
      closely related species B. mucronatus, but that similar sequences are not present
      in any other nematode studied to date. The B. xylophilus gene is expressed solely
      in the oesophageal gland cells of the nematode and the protein is present in the
      nematode's secretions. The deduced amino acid sequence of the gene is very
      similar to glycosyl hydrolase family 16 proteins. The recombinant protein,
      expressed in Escherichia coli, preferentially hydrolysed the beta-1,3-glucan
      laminarin, and had very low levels of activity on beta-1,3-1,4-glucan, lichenan
      and barley beta-glucan. Laminarin was degraded in an endoglucanase mode by the
      enzyme. The optimal temperature and pH for activity of the recombinant enzyme
      were 65 degrees C and pH 4.9. The protein is probably important in allowing the
      nematodes to feed on fungi. Sequence comparisons suggest that the gene encoding
      the endo-beta-1,3-glucanase was acquired by horizontal gene transfer from
      bacteria. B. xylophilus therefore contains genes that have been acquired by this
      process from both bacteria and fungi. These findings support the idea that
      multiple independent horizontal gene transfer events have helped in shaping the
      evolution of several different life strategies in nematodes.

PMID- 15727562
TI  - Mitochondrial reactive oxygen species regulate the temporal activation of nuclear
      factor kappaB to modulate tumour necrosis factor-induced apoptosis: evidence from
      mitochondria-targeted antioxidants.
AB  - ROS (reactive oxygen species) from mitochondrial and non-mitochondrial sources
      have been implicated in TNFalpha (tumour necrosis factor alpha)-mediated
      signalling. In the present study, a new class of specific mitochondria-targeted
      antioxidants were used to explore directly the role of mitochondrial ROS in TNF
      induced apoptosis. MitoVit E {[2-(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1
      benzopyran-2-yl)ethyl]triphenylphosphonium bromide} (vitamin E attached to a
      lipophilic cation that facilitates accumulation of the antioxidant in the
      mitochondrial matrix) enhanced TNF-induced apoptosis of U937 cells. In time
      course analyses, cleavage and activation of caspase 8 in response to TNF were not
      affected by MitoVit E, whereas the activation of caspase 3 was significantly
      increased. Furthermore, there was an increased cleavage of the proapoptotic Bcl-2
      family member Bid and an increased release of cytochrome c from mitochondria, in
      cells treated with TNF in the presence of MitoVit E. We considered several
      mechanisms by which MitoVit E might accelerate TNF-induced apoptosis including
      mitochondrial integrity (ATP/ADP levels and permeability transition), alterations
      in calcium homoeostasis and transcription factor activation. Of these, only the
      transcription factor NF-kappaB (nuclear factor kappaB) was implicated. TNF caused
      maximal nuclear translocation of NF-kappaB within 15 min, compared with 1 h in
      cells pretreated with MitoVit E. Thus the accumulation of an antioxidant within
      the mitochondrial matrix enhances TNF-induced apoptosis by decreasing or delaying
      the expression of the protective antiapoptotic proteins. These results
      demonstrate that mitochondrial ROS production is a physiologically relevant
      component of the TNF signal-transduction pathway during apoptosis, and reveal a
      novel functional role for mitochondrial ROS as a temporal regulator of NF-kappaB
      activation and NF-kappaB-dependent antiapoptotic signalling.

PMID- 15727564
TI  - Tumor necrosis factor-alpha in the placenta is not elevated in pre-eclamptic
      patients despite its elevation in peripheral blood.
AB  - PROBLEM: Tumor necrosis factor-alpha (TNF-alpha) is present in human placental
      and uterine cells at the early and late stages of gestation and promotes the
      regulation of trophoblast growth and invasion. We evaluated whether TNF-alpha
      levels in the placenta and blood of pre-eclamptic women differed from those with
      normal pregnancies. METHOD OF STUDY: The subjects were 39 pregnant women carrying
      single fetuses (21 normal-pregnant and 18 pre-eclamptic patients). Their average
      gestational age at entry was 38-39 weeks. Peripheral blood was collected before
      the onset of labor and separated serum was stored at -20 degrees C. A tissue
      segment of the placenta was cut and frozen in liquid nitrogen immediately after
      delivery at -80 degrees C. The frozen placental tissue was added to phosphate
      buffered saline. The tissue was fully homogenized and centrifuged. Separated
      supernatant was stored at -80 degrees C. TNF-alpha levels in separated serum and
      TNF-alpha and total protein (TP) levels in separated supernatant were measured.
      The presence of TNF-alpha in the placenta was evaluated by immunohistochemistry
      in five pre-eclamptic and five normal-pregnant patients. RESULTS: Serum TNF-alpha
      levels were higher in pre-eclampsia than in normal pregnancies. However, TNF
      alpha/TP levels in the placenta did not differ significantly between the two
      groups. As for TNF-alpha immunostaining of trophoblastic cells in the placenta,
      it was weak in three and moderate in two of the normal pregnancies, while it was
      absent in two, weak in one, and moderate in two in the pre-eclampsia group.
      CONCLUSIONS: We demonstrated no significant increase in TNF-alpha/TP levels in
      the placenta in pre-eclampsia despite a significant increase in serum TNF-alpha
      levels. There was no strong immunostaining for TNF-alpha detected by
      immunohistochemistry in the pre-eclampsia group. These findings suggest that TNF
      alpha in the placenta is not a key cytokine to interfere with normal trophoblast
      invasion into the myometrium in pre-eclampsia, and that sources other than the
      placenta may contribute to the elevated levels of TNF-alpha found in the
      circulation of pre-eclamptic patients.

PMID- 15727565
TI  - Increase of activated mast cells in human endometriosis.
AB  - PROBLEM: The proliferation of stromal cells in endometriosis promotes extensive
      adhesion; therefore, the morphological analysis of stromal lesions is important
      in the investigation of the pathogenesis of endometriosis. METHOD OF STUDY: In
      this study, the morphological and numeric comparisons of degranulated mast cells
      were performed between endometriotic lesions and comparative regions (eutopic
      endometrium and normal uterine serosa) of patients with and without
      endometriosis. RESULTS: In cases of endometriosis, diffuse infiltration of
      numerous mast cells was observed throughout the stromal lesions. These mast cells
      exhibited degranulation, and scattered granules were also observed. In the
      eutopic endometrium and normal uterine serosa of both the endometriosis patients
      and the controls, mast cells were rarely detected. CONCLUSIONS: These results
      suggest that an abnormal immune response, specifically a hypersensitivity
      reaction, is strongly related to endometriosis; our findings will be helpful in
      the development of methods for the treatment of endometriosis.

PMID- 15727566
TI  - Preconception peripheral natural killer cell activity as a predictor of pregnancy
      outcome in patients with unexplained infertility.
AB  - PROBLEM: Preconception high peripheral natural killer (NK) cell activity in women
      with recurrent spontaneous abortion can predict subsequent miscarriages. We have
      examined prospectively, for the first time, the pregnancy rate in patients with
      unexplained infertility by measuring the peripheral NK activity. METHOD OF STUDY:
      We tested the peripheral NK activity of 94 infertile women who despite treatment
      were unable to conceive for 6 or more months (mean; 2.4 years). Peripheral NK
      activity was measured by a chromium-51 release cytotoxicity assay. Women were
      followed for 2 years and assessed. RESULTS: In 77 patients who were followed for
      2 years, 28 had conceived but 49 did not. The peripheral NK activity of the group
      that became pregnant (mean +/- S.D.; 34.5 +/- 13.8%) was significantly lower than
      that of non-conception group (42.3 +/- 13.3%, P = 0.017). CONCLUSIONS: Our
      finding suggests that elevated peripheral NK activity in patients with
      unexplained infertility is a risk factor for attaining pregnancy success.

PMID- 15727567
TI  - Polymorphisms within the interleukin-1 gene family and unexplained late
      intrauterine fetal death: a multi-center study.
AB  - PROBLEM: Interleukin-1 (IL-1) mediated inflammatory processes have been proposed
      to be involved in the pathogenesis of late unexplained intrauterine fetal death
      (IUFD). We determined whether common polymorphisms within the IL-1 gene locus can
      serve as candidate genes for this condition. METHOD OF STUDY: In a multi-center
      case-control study, we evaluated the -889 C/T polymorphism of the IL-1alpha gene
      (IL1A), the -511 C/T polymorphism of the IL-1beta promoter (IL1B promoter), the
      +3953 C/T polymorphism of IL-1beta exon 5 (IL1B exon 5), and a 86 base pair
      repeat in intron 2 of the IL-1 receptor antagonist gene (IL1RN) in 94 women with
      IUFD and 94 healthy controls using pyrosequencing. RESULTS: No significant
      associations were found between the presence of polymorphic alleles of IL1A (P =
      0.9), IL1B promoter (P = 0.3), IL1B exon 5 (P = 0.9), and IL1RN intron 2 (P =
      0.7) and the incidence of IUFD. In women with IUFD, polymorphisms were not
      associated with the timing of fetal death and birth weight. CONCLUSIONS:
      Polymorphisms within the IL1 gene family are not associated with the occurrence
      of IUFD overall and do not modulate the clinical characteristics of affected
      pregnancies in a large series of Caucasian women.

PMID- 15727568
TI  - Antiproliferative actions of ovine uterine serpin.
AB  - PROBLEM: Ovine uterine serpin (OvUS) is a member of the serine proteinase
      inhibitor superfamily and is the major protein produced by luminal and glandular
      epithelium of the sheep endometrium during mid to late pregnancy. The protein
      does not have prototypical proteinase inhibitory activity but can inhibit a wide
      variety of lymphocyte functions such as mitogen-induced proliferation and natural
      killer cell cytotoxicity. METHOD OF STUDY: The antiproliferative actions of OvUS
      were studied. RESULTS: It was demonstrated that, in addition to inhibiting
      lymphocyte proliferation, OvUS inhibits growth of two tumor cell lines (D17 and
      PC-3). The protein also interrupts development of pre-implantation embryos.
      Inhibition of cell proliferation is not universal, however, as OvUS did not
      inhibit growth of two non-tumorigenic cell lines (MDBK and BEND). The mechanism
      of action of inhibitory effects of OvUS is not known although experiments with
      inhibitors of protein kinase A indicate that the protein does not inhibit
      lymphocyte proliferation through this pathway. Moreover, the protein does not
      induce apoptosis. CONCLUSIONS: The finding that OvUS has antiproliferative
      activity is demonstrative of the wide range of functions exerted by members of
      the serpin superfamily. The antiproliferative property of OvUS may reflect the
      role of the protein during pregnancy and may be exploitable for design of new
      antiproliferative drugs.

PMID- 15727569
TI  - Role of apoptosis controlled by cytochrome c released from mitochondria for
      luteal function in human granulosa cells.
AB  - PROBLEM: The aim of this study was to investigate the relationship between
      apoptosis by the mitochondrial pathway and luteal function in human granulosa
      cells. METHOD OF STUDY: Granulosa cells were obtained by ultrasound-guided
      follicular aspiration from patients undergoing in vitro fertilization and embryo
      transfer. After the addition of RU486, cells were stained with a mitochondria
      specific fluorescent dye, MitoTracker Red CM x Ros. Using flow cytometry and
      National Institute of Health image, the mitochondrial fluorescent area was
      measured. After staining with Hoechst 33258 dye, the number of apoptotic bodies
      per 1000 cells were counted at random on photomicrographs. Homogenates were used
      for sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot
      analysis using antibodies against cytochrome c or caspase-3. RESULTS: The
      incidence of apoptotic bodies increased and the mitochondrial membrane potential
      decreased time dependently. The opposite effect was observed dose dependently
      with RU486 treatment. Western blot analysis showed increased cytochrome c
      expression, after treatment with 1-2 microg/mL of RU486 which then decreased with
      5-10 microg/mL of RU486. Caspase-3 expression increased dose dependently with
      RU486. CONCLUSIONS: These results suggest that the activation of caspase-3 caused
      by cytochrome c released from mitochondria plays an important role in apoptosis
      related luteal function in human granulosa cells.

PMID- 15727571
TI  - A new series in Allergy: rare immunological respiratory diseases.

PMID- 15727570
TI  - Up-regulation of vascular endothelial growth factor-C by nicotine in cervical
      cancer cell lines.
AB  - PROBLEM: Smoking and infection with human papilloma virus (HPV) are major risk
      factors for cervical cancer. Our earlier work shows that nicotine enhances
      cellular proliferation of cervical cancer cell lines by up-regulating epidermal
      growth factor (EGF) and its receptor EGF-R, which leads to increased insulin-like
      growth factor II in vitro. We found that the vascular endothelial growth factor
      (VEGF)-C, one of the five isoforms of VEGF, may be specifically involved in
      lymphogenic metastasis of cervical cancer. This has prompted us to study if in
      vitro nicotine treatment will up-regulate VEGF-C alongside EGF-R levels, while
      down regulating the anti-proliferative transforming growth factor (TGF)-beta
      levels in HPV positive cervical cancer cell lines. METHOD OF STUDY: Cervical
      cancer cell lines CaSki, HeLa and ME-180, were cultured in serum free DMEM medium
      for 24-hr, and treated with 10 ng/mL nicotine in the medium supplemented with 10%
      fetal bovine serum. A group of untreated cells served as controls. The cells were
      cultured in chamber slides (for immunofluorescent antibody assay) as well as
      microtiter plate wells (for BrdU cell proliferation assay). The cellular levels
      of VEGF-C, TGF-beta, EGF-R and HPV-E6 (early protein 6) were measured by a semi
      quantitative immunofluorescent antibody assay. The cell proliferation and
      immunofluorescent assay data were analyzed by a Student's t-test. RESULTS: Cell
      proliferation was significantly increased after nicotine treatment in all the
      cell lines. The VEGF-C levels were significantly increased, while TGF-beta levels
      were decreased by nicotine in all the cell lines (P < 0.00001). EGF-R levels were
      also significantly increased after nicotine treatment in HeLa and ME-180, while
      HPV-E6 levels remained unchanged in all three. CONCLUSIONS: Nicotine up regulates
      expression of cell proliferative VEGF-C and EGF-R, while down-regulating anti
      proliferative TGF-beta. Our data suggest that nicotine in circulation and in
      cervical squamous epithelial cells may promote not only rapid tumor growth but
      its lympho-angiogenic spread (VEGF-C) as well. It appears that nicotine does not
      promote HPV spread in the cervical cancer cells.

PMID- 15727572
TI  - Idiopathic pulmonary fibrosis.

PMID- 15727573
TI  - The SAFE project: 'plant food allergies: field to table strategies for reducing
      their incidence in Europe' an EC-funded study.
AB  - The true prevalence of food allergy as an IgE mediated reaction is still under
      discussion. Using apple as a model allergen source a multidisciplinary consortium
      worked together at developing various strategies for reducing the incidence of
      fruit allergies in an EC-funded project. Patient allergen profiles were
      established using in vitro and in vivo tests with respect to geographic area and
      mild or severe symptoms. Apple allergens (Mal d 1-Mal d 4) were characterised,
      variants identified, cloned and sequenced. These individual allergens were used
      to increase the sensitivity and specificity of diagnosis. Furthermore, they
      provided better prognosis of disease severity. RT-PCR and ELISA were developed
      for determining the allergen specific mRNA and expressed allergenic protein in a
      large number of apple cultivars. Similarly, changes in allergen characteristics
      from harvest through storage to processing and the impact of agronomic practices
      were investigated. Allergen genes were mapped on a molecular linkage map of
      apple. The biological function of Mal d 1 was studied using the RNA interference
      strategy. Finally, consumer attitudes in Northern, Central and Southern Europe
      were gauged on the acceptability of low allergen cultivars or a GMO and its
      impact on product quality.

PMID- 15727574
TI  - Epidemiology of life-threatening and lethal anaphylaxis: a review.
AB  - Severe anaphylaxis is a systemic reaction affecting two or more organs or systems
      and is due to the release of active mediators from mast cells and basophils. A
      four-grade classification routinely places 'severe' anaphylaxis in grades 3 and 4
      (death could be graded as grade 5). Studies are underway to determine the
      prevalence of severe and lethal anaphylaxis in different populations and the
      relative frequencies of food, drug, latex and Hymenoptera anaphylaxis. These
      studies will also analyse the risk arising from the lack of preventive measures
      applied in schools (personalized management protocols) and from the insufficient
      use of self-injected adrenalin. Allergy-related conditions may account for 0.2-1%
      of emergency consultations. Severe anaphylaxis affects 1-3 per 10 000 people, but
      for the United States and Australia figures are even higher. It is estimated to
      cause death in 0.65-2% of patients, i.e. 1-3 per million people. An increased
      prevalence has been revealed by monitoring hospitalized populations by reference
      to the international classification of disease (ICD) codes. The relative
      frequency of aetiological factors of allergy (food, drugs, insects and latex)
      varies in different studies. Food, drug and Hymenoptera allergies are potentially
      lethal. The risk of food-mediated anaphylaxis can be assessed from the number of
      personalized management protocols in French schools: 0.065%. Another means of
      assessment may be the rate of adrenalin prescriptions. However, an overestimation
      of the anaphylaxis risk may result from this method (0.95% of Canadian children).
      Data from the literature leads to several possibilities. First, a definition of
      severe anaphylaxis should be agreed. Secondly, prospective, multicentre
      enquiries, using ICD codes, should be implemented. Moreover, the high number of
      anaphylaxis cases for which the aetiology is not identified, and the variation in
      aetiology in the published series, indicate that a closer cooperation between
      emergency specialists and allergists is essential.

PMID- 15727575
TI  - Nasal polyposis and its impact on quality of life: comparison between the effects
      of medical and surgical treatments.
AB  - BACKGROUND: Nasal polyposis (NP) is not a life-threatening disorder but may have
      a great impact on the quality of life (QoL). The objective of this study: (i) to
      investigate the health burden incurred by NP compared with the Spanish general
      population using the Short Form-36 Health Survey (SF-36) questionnaire; (ii) to
      compare the QoL outcome after medical or surgical treatment; and (iii) to assess
      and compare the effect of medical and surgical treatment on nasal symptoms.
      METHODS: About 109 patients with nasal polyps were included. Fifty-three patients
      were randomly allocated to receive oral prednisone for 2 weeks and 56 to undergo
      endoscopic sinus surgery. All patients administered intranasal budesonide for 12
      months. Patients were evaluated for nasal symptoms, polyp size, and QoL. RESULTS:
      In comparison with the Spanish general population, patients with NP had worse
      scores on all SF-36 domains except for physical functioning. Nonasthmatic
      patients with NP had better QoL than asthmatic patients with NP on role physical
      functioning, body pain, and vitality (P <0.05). At 6 and 12 months, a significant
      improvement on all of SF-36 domains was observed after both medical and surgical
      treatment reaching the levels of general population (P <0.05). Nasal symptoms and
      polyp size improved after both medical and surgical treatment at 6 and 12 months
      (P <0.05). CONCLUSION: These results suggest that NP has considerable impact on a
      patient's QoL and that both medical and surgical treatment led to similar effects
      in improving QoL.

PMID- 15727576
TI  - Secretoneurin is released into human airways by topical histamine but not
      capsaicin.
AB  - BACKGROUND: The neuropeptide secretoneurin, with potential relevance to leukocyte
      trafficking, is present in nerves of the nasal mucosa in allergic rhinitis and
      may be released in response to allergen and histamine exposure. There is no
      information on the occurrence and mechanisms of release of secretoneurin in
      healthy human airways. METHODS: The presence of secretoneurin in nasal biopsies
      and its release in response to nasal capsaicin and histamine challenges were
      examined. Symptoms and lavage fluid levels of fucose were recorded as markers of
      effects in part produced by neural activity. Bronchial histamine challenges
      followed by sputum induction and analysis of secretoneurin were also carried out.
      RESULTS: Nerves displaying secretoneurin immunoreactivity abounded in the nasal
      mucosa. Nasal capsaicin challenge produced local pain (P <0.05) and increased the
      levels of fucose (P <0.05), but failed to affect the levels of secretoneurin.
      Nasal histamine challenge produced symptoms (P <0.05) and increased the mucosal
      output of secretoneurin (P <0.05) and fucose (P <0.05). Bronchial histamine
      challenge increased the sputum levels of secretoneurin (P <0.05). CONCLUSIONS: We
      conclude that secretoneurin is present in healthy human airways and that
      histamine evokes its release in both nasal and bronchial mucosae. The present
      observations support the possibility that secretoneurin is involved in histamine
      dependent responses of the human airway mucosa.

PMID- 15727578
TI  - Exhaled nitric oxide in a population-based study of asthma and allergy in
      schoolchildren.
AB  - Exhaled nitric oxide (NO) reflects inflammation in the lower airways and is well
      adapted for use in children. The aims of this study were to investigate the
      distribution of the fraction of expired NO (FENO) in school children and to
      compare FENO and spirometry in relation to the International Study of Asthma and
      Allergies in Childhood questionnaire. The study was performed in 959 randomly
      selected 13-14-year-old school children in Uppsala, Sweden. Exhaled NO was
      measured at an inhalation rate of 0.1 l/s (FENO0.1) and a spirometric test was
      performed and data from these measurements were related to questionnaire data.
      Exhaled NO was measured according to American Thoracic Society recommendations,
      except the use of a mouth wash and an exhalation flow rate of 0.1 l/s. The
      distribution of the mean FENO0.1 values was skewed, with a preponderance of very
      low levels and a widespread tail of values ranging up to 102 parts per billion
      (ppb). Boys exhibited significantly higher mean FENO0.1 values than girls, 5.2
      (4.7-5.7) vs 4.4 (4.0-4.8) ppb (geometric mean and 95% CI), P <0.01). Children
      who reported wheezing in the last year had higher FENO0.1 values than children
      that had not, 8.5 (7.1-10.2) vs 4.3 (4.0-4.6) ppb, P <0.001). The same
      association was found to most symptoms indicating hay fever and eczema. In
      contrast to this, only weak or inconsistent associations were found between
      asthma and spirometric indices. Exhaled NO levels were found to be independently
      related to male gender, wheeze and rhinoconjuctivitis but not to current eczema.
      In conclusion, exhaled NO was closely associated with reported asthma and allergy
      symptoms whereas spirometric indices such as percent predicted forced expiratory
      volume in 1 s were not. As most asthma cases in a population are mild, the
      findings suggest that exhaled NO is a sensitive marker of asthma and allergy.

PMID- 15727577
TI  - Determinants of increased exhaled nitric oxide in patients with suspected asthma.
AB  - Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic
      inflammation, but it is unclear whether FENO in clinical use selects patients
      primarily according to their atopic or asthmatic status. The aim of this study
      was to investigate the determinants of increased FENO in patients with suspected
      asthma, by means of multinomial logistic regression analysis. The FENO of 132
      patients referred because of symptoms suggestive of asthma were studied, and the
      explanatory factors tested included atopy according to prick skin tests, clinical
      asthma according to lung function tests, sputum eosinophilia and bronchial
      hyperresponsiveness (BHR). Slightly elevated FE(NO) levels were significantly
      explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P=0.04), but
      for high levels of FE(NO) (> or =3 SD of predicted), clinical asthma (OR: 16.3;
      95% CI: 5.4-49.7; P <0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0;
      P >0.0001) were the characteristics with the highest prediction, followed by
      atopy and BHR. A significant interaction between asthma and atopy was observed
      relating to the effect on high FENO, but further analyses stratified by atopy
      showed significant associations between asthma and high FENO both in atopic and
      nonatopic patients. We conclude that in patients with symptoms suggesting asthma,
      slightly elevated and high levels of FENO are associated with sputum
      eosinophilia, whereas asthma is significantly associated only with high levels of
      FENO, irrespective of atopy. The results suggest that FENO is primarily a marker
      of airway eosinophilia, and that only high values of FENO may be useful to
      identify patients with atopic or nonatopic asthma.

PMID- 15727579
TI  - Acid-base equilibrium in exhaled breath condensate of allergic asthmatic
      children.
AB  - BACKGROUND: The dysregulation of airway pH control may have a role in asthma
      pathophysiology. The measurement of exhaled breath condensate (EBC) pH and
      ammonia levels may be used as a noninvasive method to study acid-base status in
      the airway of asthmatics. METHODS: Exhaled breath condensate from 29 allergic
      stable asthmatic children and 13 healthy controls was collected by cooling
      exhaled air during tidal breathing. Ammonia was measured by high-performance
      liquid chromatography with fluorescence detection. pH was measured after
      deaeration of EBC samples by bubbling with argon. The children also underwent
      FENO measurement. RESULTS: Both pH and ammonia values in EBC were significantly
      lower in the asthmatics than in the control group [pH: ICS-treated (median and
      interquartile range) 7.70 (7.62-7.74), steroid-naive 7.53 (7.41-7.68), controls
      7.85 (7.80-7.90), P <0.01 and P <0.001, respectively; ammonia: ICS-treated 476.17
      microM (282.50-594.80), steroid-naive 253.24 microM (173.43-416.08), controls
      788.30 microM (587.29-1310.39), P < 0.05 and P <0.001, respectively]. Both pH and
      ammonia values were higher in ICS-treated than in steroid-naive asthmatic
      children. There was a significant correlation between EBC pH and ammonia
      concentrations. CONCLUSIONS: These data show that EBC pH values of stable
      asthmatic children are lower compared with those of healthy controls and
      positively correlated with ammonia concentrations, supporting the hypothesis that
      airway acidification may have a role in the pathobiology of allergic asthma.

PMID- 15727580
TI  - A new tool to assess and monitor the burden of chronic cough on quality of life:
      Chronic Cough Impact Questionnaire.
AB  - INTRODUCTION: Chronic cough, one of the most frequent causes for a patient to
      consult a medical practitioner, limits the course of normal activities in
      everyday life of the patient affected (work, physical activities, social
      relations, night sleep). By now, there are few validated questionnaires for the
      evaluation of the impact of this symptom in the patient's quality of life (QoL).
      For this reason, we created a new questionnaire for the assessment of QoL in
      patients affected by chronic cough (Chronic Cough Impact Questionnaire, CCIQ).
      MATERIALS AND METHODS: In the development procedure of CCIQ an initial
      questionnaire of 40 items was compiled and given to a first pool of 170 patients,
      each coming to our attention because of chronic cough; then the 25 most
      significant items were detected and converted into questions evaluating the
      answers on a Likert scale of five steps. Consequently, this final questionnaire
      underwent a validation procedure to assess its construct validity, internal
      consistency, reliability, and responsiveness. 95 patients (44.2% F, 55.8% M) were
      evaluated (age 53.69 +/- 11.7 years). RESULTS: Following a statistical analysis,
      CCIQ showed a four-dimensional structure and good levels of internal consistency
      for the extracted factors: sleep/concentration (79.98), relationship (86.98),
      daily life impact (69.04), and mood (65.41). In stable conditions CCIQ showed a
      good reliability, ranged between 0.67 and 0.88. Responsiveness to clinical
      changes was accomplished. DISCUSSION: These results provide evidence that CCIQ
      has specificity enough for being a valid tool for detecting the relative burden
      of cough on subjective well-being, and for obtaining a global evaluation both of
      chronic cough impact and of treatments for it, taking into account the patient's
      point of view. The CCIQ was easily and quickly filled in by the patients while
      waiting, and it was accepted by the patients.

PMID- 15727581
TI  - Improvement of chronic idiopathic urticaria with L-thyroxine: a new TSH role in
      immune response?
AB  - BACKGROUND: The association between chronic idiopathic urticaria (CIU) and
      autoimmune thyroiditis (AT) is known, as well as major prevalence of antithyroid
      antibodies in the allergical subjects and other autoimmune diseases. We have
      evaluated the effects of l-thyroxine on clinical symptoms of CIU in AT patients
      suggesting the hypothesis of a new thyroid-stimulating hormone (TSH) role in
      immune system. METHODS: In 20 female patients with CIU + AT, both hypothyroid and
      euthyroid, we have investigated the therapeutic effects of l-thyroxine dosed to
      suppress the TSH. Free-T3, Free-T4, TSH, antithyroperoxidase and
      antithyroglobulin antibodies, total immunoglobulin (Ig)E, Rheuma test and eritro
      sedimentation rate were monitored during treatment. RESULTS: In 16 patients a
      strong decrease of urticaria symptoms has happened after 12 weeks. The TPO Ab and
      HTG Ab clearly decreased in 14 patients. Furthermore, in two patients with
      rheumatoid arthritis and in two patients with pollen allergy a strong decrease of
      rheuma test titer and total IgE has happened. CONCLUSION: The reason of AT is
      associated to CIU and others allergical and autoimmune diseases is poorly known.
      The exclusive hormonal therapy reduces the symptoms of CIU and inflammatory
      response in many chronic diseases associated to AT. We suggest a stimulatory
      effect of TSH able to produce considerable changes of the immune response and
      immune tolerance in patients with AT causing target organs damage. The causal
      mechanism involves immune, nervous and endocrine system, sharing a common set of
      hormones, cytokines and receptors, in a unique totally integrated loop (the neuro
      immuno-endocrine axis).

PMID- 15727582
TI  - Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a
      double-blind placebo-controlled trial.
AB  - BACKGROUND: Probiotic bacteria are suggested to reduce symptoms of the atopic
      eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to
      investigate whether probiotic bacteria have any beneficial effect on AEDS.
      METHODS: Follow-up of severity of AEDS by the Severity Scoring of Atopic
      Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA)
      receiving, in a randomized double-blinded manner, concomitant with elimination
      diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic
      strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was
      diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120
      infants. RESULTS: In the whole group, mean SCORAD (at baseline 32.5) decreased by
      65%, but with no differences between treatment groups immediately or 4 weeks
      after the treatment. No treatment differences were observed in infants with CMA
      either. In IgE-sensitized infants, however, the LGG group showed a greater
      reduction in SCORAD than did the placebo group, -26.1 vs-19.8 (P=0.036), from
      baseline to 4 weeks after the treatment. Exclusion of infants who had received
      antibiotics during the study reinforced the findings in the IgE-sensitized
      subgroup. CONCLUSION: Treatment with LGG may alleviate AEDS symptoms in IgE
      sensitized infants but not in non-IgE-sensitized infants.

PMID- 15727583
TI  - Evaluation of food-pollen cross-reactivity by nose-mouth cross-challenge in
      pollinosis with oral allergy syndrome.
AB  - BACKGROUND: Oral allergy syndrome (OAS) is often associated with pollen-induced
      rhinitis, and there are preferential associations between causative substances.
      If OAS and rhinitis are both immunoglobulin (Ig)E-mediated and there are cross
      reacting proteins, it is expected that similar reactions can be elicited in the
      nose and mouth. In order to test this hypothesis we performed a series of 'cross
      challenges' with foods and pollens in both the nose and the mouth. METHODS: Nine
      patients with ascertained OAS due to vegetables and rhinitis due to pollens were
      studied. On the first day a nasal challenge with pollen extracts and an oral
      challenge with fresh food was carried out. After a week, washout nasal challenge
      with food and an oral challenge with pollens were performed. Immediate symptoms,
      mucosal tryptase and soluble eosinophil cationic protein (ECP) were assessed
      after each challenge. RESULTS: The administration of pollen into the nose and
      food into the mouth elicited symptoms as expected, but the cross-challenge had no
      clinical effect. In parallel, tryptase and ECP increased after nasal challenge
      with pollens, whereas foods did not elicit a measurable response. CONCLUSION: The
      cross-reactivity between foods and pollens, when evaluated at the shock organ,
      was not clinically evident. This data can be explained with a low concentration
      of cross-reagent epitopes in pollen extracts and food homogenized because of
      degradation. The different behaviour upon challenge suggests that different
      immunological mechanisms may act in the nose and mouth.

PMID- 15727584
TI  - IgE antibodies to omega-5 gliadin in children with wheat-induced anaphylaxis.
AB  - BACKGROUND: Wheat can cause severe immunoglobulin E (IgE)-mediated systemic
      reactions including anaphylaxis but knowledge on relevant wheat allergens at the
      molecular level is scanty. METHODS: Seven children (aged from 6 months to 13
      years) experiencing from 2 to 10 anaphylactic reactions in a year after eating
      food-containing wheat were examined. Purified omega-5 gliadin was used as an
      allergen in IgE enzyme-linked immunosorbent assay (ELISA) and in skin prick
      testing (SPT). Wheat CAP radioallergosorbent test (RAST) and SPT were also
      examined. RESULTS: All seven anaphylactic children, but none of 15 control
      subjects had IgE antibodies to omega-5 gliadin in ELISA. Five of the six tested
      anaphylactic children showed positive SPT to omega-5 and crude gliadin, and all
      seven had positive wheat CAP RAST and SPT. One child was challenged with wheat,
      which caused anaphylaxis. After adherence to a wheat-free diet four children
      remained symptomless and three experienced one to two anaphylactic reactions.
      CONCLUSION: The present results show that wheat omega-5 gliadin is a major
      sensitizing allergen in children with wheat-induced anaphylaxis. They also
      suggest that omega-5 gliadin IgE ELISA could be used as a diagnostic test for
      this severe allergy.

PMID- 15727585
TI  - Number of offspring and maternal allergy.
AB  - The consistent association seen between family size and childhood allergy has led
      to the 'hygiene hypothesis', namely that a lower frequency of infections in early
      childhood is associated with an increased risk of asthma and hay fever. Maternal
      atopy, however, is a strong predictor of childhood asthma and hay fever. If
      maternal atopy is inversely related to the number of siblings then the role of
      siblings in the development of childhood atopy, the basic tenet of the 'hygiene
      hypothesis', is challenged. We evaluated the association between number of
      pregnancies and number of live births with lifetime occurrence of maternal
      wheeze, asthma, allergic rhinitis, and allergic conjunctivitis in a cross
      sectional study in four areas in Italy. A total of 1755 (35-74 year old)
      nonsmoking women filled a questionnaire on reproductive history as well as on
      lifetime occurrence of symptoms/diseases. The number of live births was inversely
      related to lifetime allergic rhinitis (P-value for trend=0.031) and allergic
      conjunctivitis (P-value for trend=0.011). The odds ratios for those with 4+
      children (in comparison with those having 0-1) were: 0.53 (95% CI: 0.27-1.04) and
      0.42 (95% CI: 0.22-0.81), respectively. A similar trend was seen for number of
      pregnancies, although not statistically significant. No association was found
      between number of pregnancies and number of live births with wheeze or asthma.
      The results may be interpreted as an indication that maternal atopy influences
      pregnancy outcomes or that pregnancy itself has an effect on maternal atopy.

PMID- 15727586
TI  - Evaluation of home allergen sampling devices.
AB  - BACKGROUND: Simple, inexpensive methods of sampling from allergen reservoirs are
      necessary for large-scale studies or low-cost householder-operated allergen
      measurement. METHODS: We tested two commercial devices: the Indoor
      Biotechnologies Mitest Dust Collector and the Drager Bio-Check Allergen Control;
      two devices of our own design: the Electrostatic Cloth Sampler (ECS) and the
      Press Tape Sampler (PTS); and a Vacuum Sampler as used in many allergen studies
      (our Reference Method). Devices were used to collect dust mite allergen samples
      from 16 domestic carpets. Results were examined for correlations between the
      sampling methods. RESULTS: With mite allergen concentration expressed as
      microg/g, the Mitest, the ECS and the PTS correlated with the Reference Method
      but not with each other. When mite allergen concentration was expressed as
      microg/m2 the Mitest and the ECS correlated with the Reference Method but the PTS
      did not. In the high allergen conditions of this study, the Drager Bio-Check did
      not relate to any methods. CONCLUSIONS: The Mitest Dust Collector, the ECS and
      the PTS show performance consistent with the Reference Method. Many techniques
      can be used to collect dust mite allergen samples. More investigation is needed
      to prove any method as superior for estimating allergen exposure.

PMID- 15727587
TI  - IgE-sensitization to predatory mites and respiratory symptoms in Swedish
      greenhouse workers.
AB  - BACKGROUND: Predatory mites are used as biological pesticides worldwide for
      control of spider mites and other pests in greenhouses. The aim of this study was
      to evaluate the impact of occupational exposure to Phytoseiulus persimilis and
      Hypoaspis miles on IgE sensitization among a large group of Swedish greenhouse
      workers and to examine the relationship between exposure and allergic asthma and
      rhinoconjunctivitis. METHODS: A total of 96 greenhouse workers from the southern
      part of Sweden, who were using the predatory mites for control of pests, were
      investigated with a questionnaire and a medical examination including lung
      function test. Blood samples were taken to test for allergen-specific IgE
      antibodies to Phytoseiulus persimilis and Hypoaspis miles as well as to
      Tetranychus urticae, Dermatophagoides pteronyssinus/farinae and Tyrophagus
      putrescentiae. RESULTS: Seventeen of the 96 workers were positive in ImmunoCAP to
      predatory mites: 17 to P. persimilis (17.7%) and 14 to H. miles (14.6%). Subjects
      sensitized to predatory mites were significantly more often atopic (13/17),
      defined as a positive Phadiatop, than those who lacked IgE against these mite
      species (17/79) (P <0.01). IgE antibodies to the red spider mite T. urticae were
      present among 23 subjects. Thirty-five of the investigated subjects displayed a
      positive ImmunoCAP to at least one of the investigated mite species. Furthermore,
      sensitization to any of the mites tested was significantly associated with asthma
      (OR=9.3) and rhinoconjunctivitis (OR=4.3). CONCLUSIONS: IgE sensitization to
      predatory mites, P. persimilis and H. miles, is common among greenhouse workers.
      The findings stress the importance of improved allergen avoidance in greenhouse
      environments.

PMID- 15727588
TI  - Contact allergy from tobramycin eyedrops.
AB  - We report a patient with allergic conjunctivitis and blepharitis as a result of
      tobramycin eyedrops.

PMID- 15727589
TI  - The reduction of rhinitis symptoms by nasal filters during natural exposure to
      ragweed and grass pollen.
AB  - BACKGROUND: Prototype nasal filters were developed to collect inhaled pollen.
      This study evaluated the efficacy of the filters for prevention of rhinitis
      symptoms during acute outdoor pollen exposure. METHODS: A randomized double-blind
      design was used. Subjects (n=46) with a history of autumn exacerbation of
      rhinitis and positive skin test to ragweed, Bermuda and/or Bahia grass wore
      either active or placebo nasal filters for 2 h in autumn in a park containing
      these species. Major and Total Symptoms scores were recorded at 0, 30, 60, 90 and
      120 min. RESULTS: Subjects wearing active nasal filters had significantly reduced
      scores, at all time-points compared with placebo group (all P <0.05). Of 14
      individual symptoms measured, seven were significantly reduced (number of
      sneezes, runny nose, itchy nose, sniffles, itchy throat; itchy eyes and watery
      eyes) and another three showed a trend towards lower severity. The nasal filters
      also enabled the resolution of existing symptoms. Maximal difference in symptoms
      was seen immediately after subjects had spent 20 min sitting beside a large patch
      of ragweed. CONCLUSION: This is the first clinical trial of a nasal filter. The
      results suggest it has potential for enhancing rhinitis management during acute
      allergen exposure.

PMID- 15727590
TI  - Personal risk factors for cypress pollen allergy.

PMID- 15727591
TI  - Resolution of peanut allergy following bone marrow transplantation for primary
      immunodeficiency.
AB  - Peanut allergy is a severe and life-threatening form of food allergy. Treatments
      are being developed but the mainstays of current management remain avoidance of
      peanut and appropriate use of rescue medication. We report the case of a boy with
      peanut allergy who required a bone marrow transplant (BMT) for combined
      immunodeficiency. A food challenge, 2 years after transplant, showed that his
      peanut allergy had resolved. Allergic disorders constitute a form of immune
      deviation and while we do not advocate BMT as a treatment for peanut allergy, we
      believe this case provides an insight into the basic mechanisms involved in food
      allergy.

PMID- 15727592
TI  - Hypothesis: urbanization and the allergy epidemic--a reverse case of
      immunotherapy?

PMID- 15727593
TI  - Common variable immunodeficiency with seasonal variation.

PMID- 15727594
TI  - Educational seminars for adults with atopic dermatitis: preliminary report about
      103 patients.

PMID- 15727595
TI  - Dust and airborne endotoxin exposure in dwellings in the Strasbourg metropolitan
      area (France).

PMID- 15727597
TI  - Isolated urticaria to ondansetron and successful treatment with granisetron.

PMID- 15727596
TI  - Systemic mastocytosis associated with recurrent paroxysmal atrial fibrillation.

PMID- 15727598
TI  - Allergy to pholcodine: first case documented by oral challenge.

PMID- 15727599
TI  - Anaphylaxis after the ingestion of lamb meat.

PMID- 15727602
TI  - Bone scintigraphy appearances of incidentally diagnosed soft tissue disorders in
      musculoskeletal imaging.
AB  - Bone scintigraphy in clinical practice is primarily used for the evaluation of
      bony pathology. Incidental uptake in soft tissue is likely to be overlooked
      because it is generally believed to lack specificity. Although bone scintigraphy
      is not used as a first line investigation for musculoskeletal injuries, abnormal
      soft tissue uptake should prompt clinicians to reassess patient symptoms. The
      onus falls on the radiologist and/or nuclear physician to comment on the
      findings. Several interesting cases are presented here with findings that have
      been confirmed by other imaging modalities.

PMID- 15727603
TI  - Virtual colonoscopy: issues in implementation.
AB  - The following issues and requirements related to the implementation of a CT
      colonography (CTC) service are important: (i) policies are needed regarding the
      indications for CTC. Concomitant with this is the need for education of potential
      referrers and patients. Expectations of the procedure, particularly by general
      practitioners, may be unrealistic and indications for referral may otherwise be
      inappropriate. At present there is not general acceptance of CTC for screening
      asymptomatic persons; (ii) a flexible approach to CT protocols is useful,
      dependent on the indication for and clinical context of referral, the age and
      body habitus of the patient; (iii) attention to the issues related to the special
      skills required by the reporting radiologist. While there is a temptation to
      regard CTC interpretation as an extension of skills used in interpreting other
      cross-sectional images, there is a need to realise that there are skills required
      specific to CTC and there should be adequate provision for training; (iv) matters
      related to reporting, such as reporting format, and lesions that will be
      reported/not reported; and (v) informed consent from the patient. Information
      should be provided with regard to the limitations of CTC, the implications of a
      positive finding and radiation dosage.

PMID- 15727604
TI  - Role of duplex Doppler and power Doppler sonography in transplanted kidneys with
      acute renal parenchymal dysfunction.
AB  - The limited work published on the comparison of power Doppler sonography (PDS)
      and duplex Doppler sonography (DDS) in the assessment of acute renal allograft
      dysfunction has shown contradictory results. We compared the role of DDS and PDS
      in renal transplant recipients developing acute renal parenchymal dysfunction and
      correlated these findings with kidney biopsy, which was taken as the gold
      standard. Thirty post-renal transplant patients with acute graft dysfunction
      underwent Doppler sonography, DDS and PDS using an HDI 5000 ATL machine. Patients
      who developed graft dysfunction as a result of vascular, obstructive or other non
      parenchymal causes were excluded. All patients underwent an allograft biopsy
      within 72 h of the sonography. Based on the biopsy findings, 24 patients were
      categorized as having acute rejection, and six patients as having no rejection.
      The overall sensitivity, specificity and accuracy of DDS for evaluation of graft
      dysfunction were 54.17, 33.33, and 50.00%, respectively, and that for PDS were
      superior with 87.50, 33.30, and 76.67%, respectively. The low specificity can be
      partially attributed to the small number of cases without rejection in our study
      population. We conclude that PDS is superior to DDS in screening patients with
      acute parenchymal renal dysfunction post-transplant. However, a normal PDS
      examination does not exclude the presence of acute rejection. Power Doppler
      sonography is a useful screening test for diagnosing acute rejection but a renal
      allograft biopsy remains the gold standard for diagnosis of this condition.

PMID- 15727605
TI  - Predictors of a positive baseline bone scan in breast cancer.
AB  - The aim of this retrospective study was to determine the predictors of a positive
      bone scan in female patients with breast carcinoma. The participants were 126
      females with newly diagnosed breast carcinoma and a baseline bone scan. Patients
      who had started treatment before their bone scan were excluded. Bone scans were
      assessed as "no metastases" or "definite skeletal metastases" without knowledge
      of the patient's predictor variables. Those with "possible metastases" were
      correlated with other available imaging and clinical information, and
      recategorized as "no metastases" or "definite skeletal metastases". Results were
      compared with predictor variables. Significant predictors were increasing age, a
      higher histopathological grading and positive progesterone receptor status
      following a forward-stepwise logistic regression analysis. Axillary nodal status,
      tumour size and oestrogen receptor status did not correlate with a positive bone
      scan. Not every patient needs a staging bone scan. This study is important
      because it predicts the need for baseline scintigraphy for specific patients in
      whom skeletal metastases are more likely to be present or to develop. The
      findings are particularly valuable in times of worldwide resource scarcity and
      evolving surgical practice.

PMID- 15727606
TI  - Diagnosis and management of simple ovarian cysts: an audit.
AB  - Simple ovarian cysts are common. The aim of clinical management is to optimize
      the treatment of malignant and premalignant cysts while minimizing intervention
      for cysts likely to resolve spontaneously. In this retrospective study, ovarian
      cysts over 30 mm in diameter were detected in 90 women. Of this population, 75
      were premenopausal, 13 postmenopausal, and two had undergone a hysterectomy.
      Thirteen women presented acutely. Family history of breast, ovary or colon cancer
      was not ascertained in any of the women. None had CA125 levels performed. In 22
      cases, the cyst was aspirated; only 10 of these had follow-up ultrasound.
      Laparotomy was performed in 25 premenopausal women, the two perimenopausal women
      and eight postmenopausal women. Average cyst size was 71 mm (range 40-80 mm) in
      the laparoscopy group, and 72 mm (range 36-180 mm) in the laparotomy group. After
      initial diagnosis at ultrasound, a follow-up scan was performed 4-16 weeks later.
      The final diagnosis was ovarian neoplasm in 13 and hydrosalpinx in two. None had
      a malignancy. Documentation at ultrasound was often inadequate, and management of
      the women with an ovarian cyst was haphazard. Guidelines on management of simple
      ovarian cysts are likely to improve clinical practice.

PMID- 15727607
TI  - Diagnosis of pulmonary embolism: ventilation perfusion scintigraphy versus
      helical computed tomography pulmonary angiography.
AB  - The present study compared the accuracy of ventilation perfusion scintigraphy
      (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary
      embolism. This was a prospective observational study of 112 patients with
      suspected pulmonary embolism (PE) who could be studied with both investigations
      within 24 h. Results were compared to final diagnosis at completion of 6-month
      follow up, using receiver operating characteristic (ROC) analysis. Pulmonary
      embolism was diagnosed in 27 referred patients (24%). The sensitivity and
      specificity of VQS and CTPA were similar to that reported from the literature. A
      normal VQ scan had the highest negative predictive value (100%), while a high
      probability VQ scan had the highest positive predictive value (92%). There was no
      overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) =
      0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE.
      Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared
      somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach
      statistical significance. In this instance, CTPA is at least as accurate as VQS
      and may provide an opportunity to make alternative diagnoses.

PMID- 15727608
TI  - Absence of adverse early quality of life outcomes of radiation therapy in breast
      conservation therapy for early breast cancer.
AB  - The New South Wales Breast Radiation Oncology Group has completed a prospective
      multicentre study of the impact of radiation therapy (RT) on acute toxicity and
      quality of life (QoL) in women with early breast cancer treated with breast
      conservation therapy. The patient group received adjuvant breast tangential RT
      after wide local excision of breast cancer. Acute toxicity and cosmesis was
      assessed quantitatively and qualitatively. European Organization of Research and
      Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) and Perceived
      Adjustment to Chronic Illness Scale (PACIS) were the QoL instruments used. Of 175
      women, 34.3% described lethargy leading to a significant disruption to normal
      activity during RT. At week 6, this had reduced to 7.5% reporting significant
      lethargy. No negative effects on QoL were noted over the time period of RT; EORTC
      demonstrated no difference (P = 0.79). PACIS recorded a significant improvement
      in functioning (P < 0.001) from baseline to week 6. Univariate analysis on
      potential predictive patient, tumour and treatment factors demonstrated an
      association of baseline pre-RT breast discomfort with worse lethargy (P = 0.03),
      EORTC (P < 0.01) and PACIS (P < 0.01) measures. This study confirms the minimal
      impact of RT on patient functioning at 6 weeks post-treatment.

PMID- 15727609
TI  - Changes in practice of breast cancer radiotherapy 1998-2002: an Australasian
      survey.
AB  - In order to assess the impact on radiation oncology practice of the publication
      of evidence-based guidelines for technical aspects of therapeutic radiation for
      breast cancer, the Radiation Oncology Expert Advisory Group of the National
      Breast Cancer Centre conducted two postal surveys of radiation oncologists
      practising in Australia and New Zealand. Results from a survey conducted in 1998,
      prior to distribution of the guidelines, have been published previously. This
      article reports on results from a survey undertaken in 2002 and contains data
      from 102 respondents who manage women with breast cancer. The results show
      several important changes in practice since 1998, including increased use of CT
      scanning in breast cancer treatment planning and increased use of immobilization
      devices for patient treatment. There is also evidence of increased attention to
      technical aspects of treatment planning that reduce the potential risk of
      treatment toxicity. The influence of the guidelines, the wider availability of
      modern equipment and results from landmark clinical trials on change in radiation
      therapy practice is discussed.

PMID- 15727610
TI  - Trichoptysis caused by intrapulmonary teratoma: computed tomography and magnetic
      resonance imaging findings.
AB  - We describe a 9-year-old child with a history of trichoptysis caused by
      intrapulmonary teratoma and we present the CT and MRI findings of the teratoma. A
      heterogeneous mass containing cystic and solid elements was detected on both CT
      and MRI scans. Histopathological examination confirmed the diagnosis of teratoma.
      Teratomas arising from lung parenchyma, as in this case, are extremely rare in
      childhood. In the thoracic region, the most common localization of teratomas is
      the anterior mediastinal compartment. We also discuss the CT and MRI findings and
      the differential diagnosis of teratomas.

PMID- 15727611
TI  - Distinctive new form of spondyloepimetaphyseal dysplasia with severe metaphyseal
      changes similar to Jansen metaphyseal chondrodysplasia.
AB  - We report a boy with a unique, "new" form of spondyloepimetaphyseal dysplasia.
      The conspicuous features of the spinal changes were the delay in ossification of
      the cervical spine and posterior elements of the thoraco-lumbar spine. The
      vertebral bodies were of abnormal shape but of normal size and well ossified. The
      hallmark of epiphyseal changes was markedly delayed ossification (bone age). The
      severely disturbed metaphyseal ossification was similar to Jansen metaphyseal
      dysplasia. This pattern of changes has not yet been described in
      spondyloepimetaphyseal dysplasia.

PMID- 15727612
TI  - Osteogenic pulmonary metastases originating from a phyllodes tumour of the breast
      with osteosarcomatous differentiation.
AB  - Malignant phyllodes tumour is an uncommon breast neoplasm which undergoes
      osteosarcomatous differentiation in 1.3% of cases. We document the plain film, CT
      and scintigraphic features of a case of pulmonary metastases from this rare
      primary tumour.

PMID- 15727613
TI  - Magnetic resonance imaging findings of a foregut duplication cyst of the floor of
      the mouth in a fetus.
AB  - The MRI findings are described in a case of foregut duplication cyst arising from
      the floor of the mouth in a fetus.

PMID- 15727614
TI  - Gastrointestinal haemorrhage due to erosion of the duodenal wall by a biliary
      stent.
AB  - Complications from improperly placed biliary stents are not uncommon. Free loose
      wires from the ends of an uncovered stent can irritate and damage adjacent
      mucosal surfaces. Effective management can be achieved via percutaneous placement
      of a second stent to alter the orientation of the original stent.

PMID- 15727615
TI  - Bilateral persistent hyperplastic primary vitreous.
AB  - We report a case of bilateral persistent hyperplastic primary vitreous (PHPV) in
      a 5-month-old infant who presented with bilateral leukokoria. The child was
      referred for ocular ultrasound with a clinical suspicion of retinoblastoma. Grey
      scale evaluation revealed an echogenic band in the posterior segment of the left
      globe extending from the posterior surface of the lens capsule to the optic disc.
      Doppler examination revealed the presence of blood flow in the band. Ultrasound
      assessment of the contralateral globe showed an elevated mass of echogenic tissue
      in the posterior segment, in contact with the optic disc. Most cases of PHPV are
      sporadic and unilateral. Bilateral PHPV is rare. In a study by Pollard of 83
      cases, only two patients (2.4%) had bilateral PHPV. The imaging features in this
      case point toward the diagnosis of bilateral PHPV. We suggest that this entity,
      although rare, should be considered in the differential diagnosis while
      evaluating bilateral leukokoria.

PMID- 15727616
TI  - Incidental heterotopic pregnancy demonstrated on magnetic resonance imaging.
AB  - We report a case of an assisted pregnancy in an asymptomatic woman who was found
      to have an extrauterine mass on ultrasound and MRI. This complex mass had
      equivocal imaging features and was found to be a ruptured ovarian ectopic
      pregnancy at surgery. This case illustrates that vigilance is required regarding
      the possibility of coexisting ectopic and intrauterine pregnancy following
      assisted conception, even in entirely asymptomatic cases.

PMID- 15727617
TI  - Cerebral melioidosis.
AB  - Two cases of cerebral melioidosis are presented to illustrate the clinical
      presentation and progress and to highlight the radiological features.

PMID- 15727618
TI  - Mesenteric panniculitis versus pancreatitis: a computed tomography diagnostic
      dilemma.
AB  - A case of mesenteric panniculitis is described in a patient with CT features
      mimicking pancreatitis. Emphasis is on the important CT features for accurate
      diagnosis.

PMID- 15727619
TI  - RE: Radiology by non-radiologists.

PMID- 15727620
TI  - RE: Intussusception due to pathologic lead points.

PMID- 15727629
TI  - Getting to grips with hand eczema: measuring skin disease severity objectively.

PMID- 15727630
TI  - Atopic dermatitis and the 'hygiene hypothesis': too clean to be true?
AB  - BACKGROUND: The so-called 'hygiene hypothesis' postulates an inverse relationship
      between atopic dermatitis (AD) and an environment that leads to increased
      pathogen exposure. OBJECTIVES: We sought to systematically identify, summarize
      and critically appraise: (i) the epidemiological evidence to suggest that
      environmental exposures that lead to an increase in microbial burden reduce the
      risk of AD; (ii) whether any specific infections have been shown to reduce AD
      risk; (iii) whether there is a link between immunizations, use of antibiotics and
      AD risk; and (iv) to comment on the new therapeutic approaches in AD that have
      evolved out of the 'hygiene hypothesis'. METHODS: We searched Medline from 1966
      until August 2004 to identify relevant studies for inclusion. Differences in
      study design and populations did not allow formal meta-analysis. Studies were
      therefore described qualitatively. RESULTS: We identified 64 studies that were
      relevant to our review, 27 (42%) of which were of prospective design. There was
      prospective evidence to support an inverse relationship between AD and
      endotoxins, early day care and animal exposure. Two well-designed cohort studies
      have found a positive association between infections in early life and AD, and
      measles vaccination and AD. Antibiotic use was consistently associated with an
      increase in AD risk even into the antenatal period, although a few studies did
      not reach conventional statistical significance. A few small randomized
      controlled trials have suggested that probiotics can reduce AD severity and that
      probiotics may also be able to prevent AD to some degree. CONCLUSIONS: Although
      population-based studies have suggested a consistent inverse relationship between
      AD and increasing family size, this does not seem to be explained by a
      straightforward increased exposure to a single environmental pathogen. The effect
      seen with early day care, endotoxin and animal exposure may be due to a
      nonpathogenic microbial stimulus of a chronic or recurrent nature. This would
      also explain the risk increase associated with antibiotic use. Caution should
      prevail in the prescribing of antibiotics early in life, especially in children
      with a family history of AD. Larger well-designed pragmatic trials on probiotics
      and the prevention and treatment of AD are now needed to inform whether such
      interventions should be used in routine clinical practice.

PMID- 15727631
TI  - Glutathione enhances fibroblast collagen contraction and protects keratinocytes
      from apoptosis in hyperglycaemic culture.
AB  - BACKGROUND: Cutaneous wound healing is relatively slow in patients with diabetes.
      OBJECTIVES: To test the hypothesis that this defect in healing of wounds in
      patients with diabetes results from dysfunction of skin fibroblasts and epidermal
      keratinocytes and that this dysfunction is related to disrupted intracellular
      glutathione (GSH) homeostasis. METHODS: We investigated the effects of esterified
      GSH on the contraction of fibroblasts in a fibroblast-populated collagen lattice
      and on keratinocyte apoptosis. RESULTS: High glucose medium (hyperglycaemia)
      reduced the contraction ability of fibroblasts (P < 0.05). The normalization of
      glucose medium concentrations for hyperglycaemic fibroblasts did not restore the
      contraction capacity. The percentage of apoptotic keratinocytes was statistically
      higher in hyperglycaemic cells (P < 0.05). GSH media concentrations ranging from
      0.1 to 100 micromol L(-1) restored the ability of hyperglycaemic fibroblasts to
      contract the gels in a concentration-dependent manner. Primary human
      keratinocytes grown in hyperglycaemic medium were more susceptible to apoptosis,
      and treatment with esterified GSH rescued the keratinocytes from apoptosis.
      CONCLUSIONS: These data suggest that intracellular GSH can normalize skin cell
      functions disrupted by in vitro cell growth under hyperglycaemic conditions.

PMID- 15727632
TI  - Insulin-like growth factor binding protein-3 (IGFBP-3) localizes to and modulates
      proliferative epidermal keratinocytes in vivo.
AB  - BACKGROUND: The colocalization of insulin-like growth factor binding protein-3
      (IGFBP-3) and IGF-I receptor (IGF-IR) in the basal/germinative layer of the
      epidermis suggests a key role in modulating epidermal homeostasis. OBJECTIVES: We
      aimed to clarify both the specific cellular localization and the effect of excess
      epidermal IGFBP-3 on keratinocyte proliferation. METHODS: (i) Total RNA was
      isolated from fluorescence-activated cell sorted basal human keratinocyte
      subtypes [keratinocyte stem cells, transit amplifying keratinocytes (TA),
      postmitotic differentiating keratinocytes (PMD)], and real-time polymerase chain
      reaction analysis was used to determine the abundance of IGFBP-3 and IGF-IR
      mRNAs. (ii) An IGFBP-3 transgenic mouse model was then used to assess the effect
      of excess epidermal IGFBP-3 on keratinocyte proliferation. Excess epidermal IGFBP
      3 mRNA and protein was determined by in situ hybridization and
      immunohistochemistry, respectively. RESULTS: (i) The highest levels of IGFBP-3
      mRNA were detected in TA keratinocytes, in contrast to IGF-IR mRNA levels which
      were highest in PMD keratinocytes. (ii) Elevated human IGFBP-3 mRNA and protein
      was confirmed in the epidermis of skin derived from transgenic mice. Excess IGFBP
      3 reduced the relative percentage of proliferative keratinocytes (Ki67 positive)
      irrespective of skin location (belly, back and tail). Thus, in the epidermis,
      IGFBP-3 mRNA is highly expressed by proliferative keratinocytes (TA) and
      overexpression of IGFBP-3 inhibits keratinocyte proliferation. CONCLUSIONS: We
      conclude that in vivo IGFBP-3 ensures epidermal homeostasis via downregulation of
      keratinocyte proliferation, and thus modulates the early stages of keratinocyte
      differentiation.

PMID- 15727634
TI  - Procollagen type I gene expression and cell proliferation are increased in
      lipodermatosclerosis.
AB  - BACKGROUND: Lipodermatosclerosis (LDS) is characterized by a hardening and
      hyperpigmentation of lower leg skin as a consequence of chronic venous
      insufficiency. The degree of skin hardening or fibrosis associated with LDS is
      proposed to relate directly to skin breakdown and venous ulcer formation as well
      as to a subsequent delay in ulcer healing. OBJECTIVES: To determine whether
      elevated procollagen type I gene expression and increased cell proliferation are
      responsible for the fibrotic changes associated with LDS. METHODS: Skin biopsies
      were obtained from the legs of patients with varying degrees of chronic venous
      disease and were assessed for procollagen gene expression by in-situ
      hybridization and for cell proliferation by immunolocalization of proliferating
      cell nuclear antigen. RESULTS: The number of cells expressing procollagen type I
      mRNA (COL1A1) was significantly higher in the dermis of LDS-affected skin
      compared with samples from the other patient groups. In addition, there was a
      significant increase in the number of dermal fibroblasts undergoing proliferation
      in both LDS samples and skin samples prior to LDS changes compared with control
      samples. However, there was no significant difference in level of inflammation in
      biopsy samples between patient classes. CONCLUSIONS: These results suggest that
      enhanced cell proliferation and procollagen gene expression are both involved in
      LDS development. Furthermore, fibrotic changes may occur in the absence of, or
      subsequent to, any significant inflammatory response, indicating that additional
      profibrotic factors produced in the skin as a consequence of chronic venous
      insufficiency may play a role in LDS formation.

PMID- 15727633
TI  - Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic
      epidermal T cells.
AB  - BACKGROUND: 1alpha,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)], the active
      metabolite of vitamin D, exerts its activities by binding to the vitamin D
      receptor (VDR) with subsequent function as a transcription factor. Targeted
      ablation of the VDR in mice results in rickets and alopecia. OBJECTIVES: To study
      the consequences of VDR deficiency for skin physiology, and to investigate the
      mechanisms of the immunosuppressive effect of 1,25(OH)(2)D(3) on LC. METHODS: We
      studied the structural, phenotypic and functional properties of skin and
      individual skin leucocyte populations in VDR(-/-) mice. RESULTS: The lack of VDR
      induced a wide spectrum of pathologies including dermal deposition of collagen,
      enlargement of sebaceous glands, dilation of the hair follicles, development of
      epidermal cysts, increased numbers of dendritic epidermal T cells (DETC) and
      hyperkeratosis. Ageing aggravated these changes. Intriguingly, Langerhans cells
      (LC) were indistinguishable in distribution, morphology and number compared with
      controls. In vitro, LC underwent a maturation/migration process similar to LC
      from control mice. Pretreatment of epidermal cells or LC-enriched epidermal cell
      suspensions with 1,25(OH)(2)D(3) impaired LC maturation and T-cell stimulatory
      capacity from VDR(+/+) but not VDR(-/-) mice, demonstrating that LC are targets
      of vitamin D(3) and that interaction between vitamin D(3) and LC results in a
      suppression of LC activity. CONCLUSIONS: Our data imply that VDR expression
      controls dermal collagen production, hair development and growth, proliferation
      of sebaceous glands and the homeostasis of DETC. Surprisingly, VDR deficiency
      does not influence LC phenotype and function.

PMID- 15727635
TI  - Cutis laxa in hereditary gelsolin amyloidosis.
AB  - BACKGROUND: Hereditary gelsolin amyloidosis (AGel amyloidosis) is an age
      associated systemic disease with global distribution, caused by a G654A or G654T
      gelsolin gene mutation. Cutis laxa is a principal clinical manifestation of this
      disease. However, only few data on the dermatological involvement are available,
      and the pathogenesis of this amyloidosis-associated form of cutis laxa has
      remained unknown. OBJECTIVES: To elucidate the pathomechanism of this less well
      known genodermatosis. METHODS: We performed systematic clinical, histological,
      immunohistochemical and ultrastructural skin biopsy studies in 12 patients with a
      G654A gelsolin gene mutation. For comparison, skin specimens from 10 control
      subjects were analysed. RESULTS: All patients had clinically characteristic cutis
      laxa, and frequently other signs of symptomatic skin disease such as increased
      fragility and risk for intracutaneous bleeding. All patients showed cutaneous
      deposition of gelsolin amyloid (AGel), mainly attached to basement membranes or
      basal laminae of various cutaneous structures, dermal nerves and blood vessel
      walls, and elastic fibres, particularly in the lower reticular dermis. AGel often
      encircled the elastic fibres, and colocalized with amyloid P component (AP), an
      elastic fibre microfibrillar sheath-associated protein. Fragmentation and loss of
      elastic fibres, epidermal atrophy, and reduction of dermal appendages were also
      common. Antibodies to wild-type gelsolin bound to S-100-positive epidermal
      dendritic cells, a previously unrecognized immunoreaction. Patients had fewer
      gelsolin-positive dendritic cells than controls. CONCLUSIONS: Widespread skin
      involvement with AGel deposition and elastic fibre involvement are essential
      pathological features in AGel amyloidosis, and contribute to the characteristic
      cutis laxa, dramatic in old age. Codistribution of AGel and AP, with demonstrated
      specific binding affinity for amyloid fibrils, suggests that elastic fibre
      associated AP acts as a matrix for cutaneous amyloid deposition in AGel
      amyloidosis.

PMID- 15727636
TI  - Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin
      homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing
      chemokine receptor CCR7.
AB  - BACKGROUND: Adhesion molecules and chemokine receptors are involved in tissue
      specific homing of T cells to the skin and play an important role in the
      pathophysiology of cutaneous lymphoma. It has recently been reported that the
      chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the
      chemokine receptor CCR10. OBJECTIVES: To investigate the expression of CCR4, CCR7
      and CCR10 on skin-homing CLA(+) and CD4(+) T cells in the peripheral blood of
      patients with Sezary syndrome (SS), a rare leukaemic variant of cutaneous T-cell
      lymphoma. METHODS: Lymphocytes from five patients with SS, six patients with
      mycosis fungoides and four healthy volunteers were isolated and analysed using
      flow cytometry. Additionally, the T-cell receptor (TCR)-Vbeta CDR3 regions were
      cloned and sequenced in two patients. RESULTS: We found that CCR4 is expressed on
      almost all CLA(+) and CD4(+) memory T cells. Using monoclonal antibodies specific
      for single TCR-Vbeta chains we identified malignant T cells in four patients with
      SS. Importantly, we found that most but not all malignant Sezary cells expressed
      the skin-homing chemokine receptor CCR10. Additionally, we found that a
      significant proportion of these cells also expressed the lymph node-homing
      chemokine receptor CCR7. CONCLUSIONS: Our results support the concept that
      chemokine receptors play an important role in the pathophysiology of SS and
      suggest that the malignant clone may represent an expansion of skin-homing
      cutaneous 'central' memory T cells in the peripheral blood of these patients.

PMID- 15727637
TI  - The combination of complement deficiency and cigarette smoking as risk factor for
      cutaneous lupus erythematosus in men; a focus on combined C2/C4 deficiency.
AB  - BACKGROUND: Although deficiencies in the early components of the complement
      system were among the first identified genetic risk factors for systemic lupus
      erythematosus (SLE), only a few studies addressed their significance in patients
      with cutaneous LE (CLE). Among environmental factors, it was postulated that
      cigarette smoking might intervene in the pathogenesis of LE. OBJECTIVES: To
      describe the clinical and biological features of patients with CLE and a
      complement deficiency. A secondary objective was to assess cigarette smoking in
      patients with CLE. PATIENTS AND METHODS: A retrospective study including all
      patients diagnosed as having LE between 1995 and 2003 in the Dermatology
      Department of Strasbourg University Hospital. Patient charts were reviewed and
      those patients in whom a C4 and/or C2 deficiency was diagnosed were included. Two
      patients with a combined C2/C4 deficiency were analysed in detail. RESULTS: There
      were 48 females and 37 males (F/M ratio = 1.3), with a mean age of 41 years at
      diagnosis; 73% of the patients had chronic LE and 27% subacute CLE. Among 32
      screened patients, 24 patients with a mean age of 36 years had a complement
      deficiency; 17 had a C4A deficiency, five a C4B deficiency and two a combined
      C4A/C2 deficiency. A high proportion (58%) of these patients was male; 82% of the
      patients were smokers. This was especially true in males: 94% were smokers
      compared with 69% of females. CONCLUSIONS: Partial deficiency of C4, C2 or C4 and
      C2 is a common finding in patients with CLE. Most male patients with CLE are
      smokers. It is thus suggested that the combination of cigarette smoking and
      complement deficiency could be a risk factor for LE in men.

PMID- 15727638
TI  - Dermoscopy of skin lesions in two patients with xeroderma pigmentosum.
AB  - BACKGROUND: Xeroderma pigmentosum (XP) is a rare disorder produced by a genetic
      defect in the repair of DNA damage caused by ultraviolet radiation. The early
      diagnosis of malignant skin tumours is crucial in the survival of patients with
      XP, but this is not easy even for experienced dermatologists due to the presence
      of a high number of actinic lesions. Dermoscopy is a new diagnostic method that
      increases the diagnostic accuracy for skin tumours. OBJECTIVES: To describe the
      clinical and dermoscopic features of different benign and malignant lesions
      [focusing on malignant melanoma, basal cell carcinoma (BCC) and benign
      melanocytic naevi] in two patients with XP. METHODS: Three dermatologists with
      experience in pigmented skin lesions and dermoscopy examined two siblings with XP
      over a period of 54 months. Diagnosis of skin tumours was obtained using clinical
      examination and dermoscopy with 10-fold magnification and digital images. All the
      tumours with criteria of malignancy were excised for further histopathological
      analyses. RESULTS: Multiple skin tumours showing some degree of pigmentation were
      detected in the patients. Clinical and dermoscopic examination allowed the
      discrimination of four melanomas (three of them in situ), 26 BCCs and five
      dysplastic naevi from other pigmented skin lesions. The features and parameters
      previously described for dermoscopy were shown to be appropriate for the
      recognition of tumours in our patients with XP. Generalized actinic lentigos were
      distinguished from BCCs by the presence of a delicate brown pigmented network.
      Fine vessels from poikiloderma were differentiated from the arborizing
      telangiectasia of BCC. CONCLUSIONS: The dermoscopic findings in the tumours were
      similar to those previously described in patients not affected by XP. Diagnosis
      by dermoscopic pattern analyses allowed a correct classification of malignant
      tumours in these cases.

PMID- 15727639
TI  - Topical aminolaevulinic acid-based photodynamic therapy as a treatment option for
      psoriasis? Results of a randomized, observer-blinded study.
AB  - BACKGROUND: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has
      recently been tried in small open studies for several inflammatory dermatoses
      including psoriasis. OBJECTIVES: The purpose of this randomized, within patient
      comparison study was to investigate whether topical ALA-based PDT using a range
      of light doses can induce a satisfactory response in localized psoriasis.
      PATIENTS AND METHODS: Twenty-nine patients with chronic plaque type psoriasis
      were enrolled in the study. After keratolytic pretreatment three psoriatic
      plaques in each patient were randomly allocated to PDT with 1% ALA and a light
      dose of 5 J cm(-2), 10 J cm(-2) or 20 J cm(-2), respectively. Treatment was
      performed twice weekly until complete clearance or for a maximum of 12
      irradiations. As a measure of clinical response the psoriasis severity index
      (PSI) of the three target plaques was assessed separately by an observer blinded
      to the treatment at baseline, before each PDT treatment and 3-4 days after the
      last irradiation. RESULTS: Eight patients withdrew prematurely from the study.
      Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups
      by about 25%. Subsequent PDT with 20 J cm(-2) resulted in a final reduction of
      PSI by 59%, PDT with the lower doses of 10 J cm(-2) and 5 J cm(-2) decreased the
      baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy
      between 20 J cm(-2) and 10 J cm(-2) or 5 J cm(-2) was statistically significant
      (P = 0.003; P = 0.02), whereas no difference was found between 10 J cm(-2) and 5
      J cm(-2) (P = 0.4). All patients reported some degree of PDT-induced stinging or
      burning during irradiation. CONCLUSIONS: The unsatisfactory clinical response and
      frequent occurrence of pain during and after irradiation renders topical ALA
      based PDT an inadequate treatment option for psoriasis.

PMID- 15727640
TI  - Darier's disease in Singapore.
AB  - BACKGROUND: Darier's disease is a rare, dominantly inherited genodermatosis.
      Although it has been well studied in caucasians, very little is known about the
      clinical spectrum of this disorder among Asians. OBJECTIVES: To determine the
      demographic and clinical profile of Asian patients with Darier's disease.
      METHODS: This is a retrospective study of all new cases of Darier's disease seen
      in our centre over a 20-year period (1982-2002). Results Twenty-four nonrelated
      cases of Darier's disease were studied. The incidence rate was 3.1 per million
      per decade. The gender distribution was 19 males and five females, and the ethnic
      origin was 21 Chinese, two Malays and one Nepalese. The peak age of onset was
      between 11 and 20 years. Sun exposure exacerbated the disease in 13 of the
      patients, and three had neuropsychiatric disorders. The disease affected
      predominantly seborrhoeic areas in 19 patients, flexural in three, acral in one
      and was segmental in one patient. Hand involvement was common and included palmar
      pits in nine patients, acrokeratosis verruciformis in four and nail changes in 12
      patients. Haemorrhagic macules were not seen. Rare features included oral mucosal
      lesions (two patients) and guttate leucoderma (three patients). Pathogens
      involved in cutaneous infections included herpes simplex virus, Staphylococcus
      aureus, Streptococcus species and Morganella morgani. All patients treated with
      oral retinoids had improvement of clinical signs. In contrast, the response to
      topical retinoids was poor. CONCLUSIONS: Compared with western studies, our
      results show a similar incidence rate, age of onset, distribution of disease
      patterns and association with neuropsychiatric disorders. Features that differ
      include co-occurrence of guttate leucoderma, rarity of acrokeratosis, absence of
      haemorrhagic macules and poor response to topical retinoids.

PMID- 15727641
TI  - Comparative study of the impact of chronic urticaria, psoriasis and atopic
      dermatitis on the quality of life.
AB  - BACKGROUND: A better management of chronic skin disorders (CSDs) requires a
      knowledge of their impact from the patient's point of view. OBJECTIVES: To
      determine which aspects of the patient's life are mainly impaired in the
      different CSDs, and provide comparative references to estimate better the real
      impact of the different CSDs. PATIENTS AND METHODS: A prospective cross-sectional
      and matched study of 1356 adult outpatients to compare the health-related quality
      of life (HRQL) profile in chronic urticaria (466 CU), psoriasis (464 PSO) and
      atopic dermatitis (426 AD), using the VQ-Dermato, a multidimensional instrument
      in French validated for CSDs. RESULTS: After adjustment for confounders, HRQL
      dimensions were differently affected in the three CSDs. The 'physical discomfort'
      dimension was more degraded in AD and CU than in PSO (P < 0.001), and 'leisure
      activities' more in PSO than in CU (P < 0.001). 'Self-perception' and 'treatment
      induced restrictions' dimensions were much less affected in CU than in PSO and AD
      (P < 0.001). In PSO, the 'daily living activities' dimension was much less
      impaired than in CU and AD (P < 0.001). No aspect of HRQL was really spared in
      AD. CONCLUSIONS: The comparison shows that CU, PSO and AD are characterized by
      completely different qualitative profiles of impact on HRQL, which are influenced
      by their clinical characteristics and usual treatment options. It underlines the
      severe impairment of CU which is often underestimated.

PMID- 15727642
TI  - Construction and validation of a photographic guide for assessing severity of
      chronic hand dermatitis.
AB  - BACKGROUND: A standardized instrument is needed to rate the overall severity of
      chronic hand dermatitis (CHD), in particular during clinical trials. OBJECTIVES:
      To design and validate a photographic guide. METHODS: Initially, five experts
      were asked to grade 50 photographs of CHD, first individually, then as a
      consensus-building group, in order to select the photographs included in the
      guide. Then, a validation session with 11 different dermatologists evaluating 28
      patients was conducted to assess the interrater reliability and test-retest
      reproducibility of the assessment of disease severity, relying on the
      photographic guide, on two consecutive days. Patient order was randomized, and
      only diseased hands were visible to prevent any bias in evaluation. RESULTS: The
      experts reached a consensus for development of a photographic guide composed of
      five severity levels and four photographs per severity level. Results of the
      validation session showed a high level of interrater reliability and test-retest
      reproducibility. CONCLUSIONS: The photographic guide is a reliable tool for
      assessing the morphological severity of hand dermatitis, and can be used as part
      of a comprehensive evaluation of disease in international multicentre clinical
      trials.

PMID- 15727643
TI  - The hand eczema severity index (HECSI): a scoring system for clinical assessment
      of hand eczema. A study of inter- and intraobserver reliability.
AB  - BACKGROUND: There is a need for a standardized clinical grading system for a more
      objective and accurate assessment of the severity of hand eczema (HE).
      OBJECTIVES: To develop and validate a scoring system called the hand eczema
      severity index (HECSI) designed for clinical assessment of HE. METHODS: Twelve
      dermatologists (observers) assessed 15 HE patients twice, with an interval of 30
      min. The study was performed blinded for the observers, and only the hands and
      wrists of the patients were visible to the observers. Agreement between the
      observers was determined by using the intraclass correlation coefficient (ICC),
      which is the correlation between (single) ratings of the same patient. RESULTS:
      ICC for total HECSI score was 0.79 at the first assessment and 0.84 at the second
      assessment. ICC for intraobserver agreement was 0.90. CONCLUSIONS: Overall
      excellent agreement existed for both inter- and intraobserver reliability and the
      scoring system is suggested for use in future clinical studies on HE. Because
      HECSI is an entirely objective assessment of clinical signs, in addition,
      inclusion of patient-rated symptoms should be considered.

PMID- 15727644
TI  - Becker's naevus: a comparative study between erbium: YAG and Q-switched
      neodymium:YAG; clinical and histopathological findings.
AB  - BACKGROUND: Becker's naevus (BN) may represent a distressing cosmetic handicap
      and a challenging issue regarding treatment. OBJECTIVES: To compare clinical and
      histopathological findings of patients with BN treated with two different lasers:
      an erbium:yttrium-aluminium-garnet (Er:YAG) system vs. a neodymium:YAG (Nd:YAG)
      laser. PATIENTS AND METHODS: In this prospective and comparative study we present
      the clinical and histopathological evolution during a 2-year follow-up of 22
      patients with BN treated with only one pass of the Er:YAG laser (n = 11) or three
      treatment sessions with the Q-switched Nd:YAG system (n = 11). RESULTS: Clinical
      evaluation 2 years after treatment with the Er:YAG laser showed complete
      clearance (100%) in 54% of the patients (n = 6) and clearance of > 50% in 100% of
      the subjects. In relation to Nd:YAG laser treatments our results echo those of
      other authors. Numerous sessions are necessary to get an acceptable clinical
      clearance rate. Only one patient showed marked clearance (51-99%) after three
      treatment sessions. Moderate (26-50%) and mild (1-25%) clearance was observed in
      45.5% (n = 5) and 27.3% (n = 3) of the patients. CONCLUSIONS: Both Er:YAG and
      Nd:YAG are safe tools to treat BN. However, in terms of pigment removal, one pass
      with Er:YAG is a superior technique to three treatment sessions with the Nd:YAG.

PMID- 15727645
TI  - Aberrantly differentiated cells in benign pilomatrixoma reflect the normal hair
      follicle: immunohistochemical analysis of Ca-binding S100A2, S100A3 and S100A6
      proteins.
AB  - BACKGROUND: Pilomatrixoma is a common benign cutaneous tumour containing
      differentiated hair matrix cells. This tumour is mainly composed of basophilic,
      transitional, shadow and squamoid cells. Although some S100 proteins are
      expressed in a tissue-specific manner in the hair follicle (e.g. S100A2 in the
      outer root sheath, S100A3 in the cortex and cuticle, and S100A6 in the inner root
      sheath), little information is available concerning their distribution in the
      aberrantly differentiated tissues of pilomatrixoma. OBJECTIVES: To characterize
      the disordered epithelial elements of pilomatrixoma by localizing S100A2, S100A3
      and S100A6 proteins. METHODS: Immunohistochemistry and dual-immunofluorescence
      microscopy were performed on 22 pilomatrixoma specimens using antibodies specific
      to the three proteins. RESULTS: Tissue-specific distribution of the S100 proteins
      investigated was preserved in the morphologically disordered tumour tissues. Anti
      S100A2 antibody stained squamoid cells and putative outer root sheath cells;
      basophilic and potential hair matrix cells were occasionally stained. S100A3
      staining was found in transitional cells and putative cortical cells, and was
      strong in both dispersed cells and hair-like structures surrounding cells which
      were presumably cuticular cells. Anti-S100A6 antibody labelled some S100A3
      negative transitional cell strands, potentially inner root sheath cells.
      CONCLUSIONS: The epithelial elements of pilomatrixoma can be characterized using
      S100 proteins as biochemical markers. Our results show that pilomatrixomas retain
      a certain degree of differentiation indicative of distinct hair-forming cells.

PMID- 15727646
TI  - Skin-infiltrating neutrophils following exposure to solar-simulated radiation
      could play an important role in photoageing of human skin.
AB  - BACKGROUND: The pathophysiology of photoageing of the skin has been studied
      extensively. Matrix metalloproteinases (MMPs) originating from keratinocytes and
      fibroblasts are thought to play a primary role in this process. Although
      neutrophils are potent producers of a wide array of proteolytic substances and
      are present in sunburned skin, their contribution to the pathophysiology of
      photoageing has been described only in murine studies. OBJECTIVES: To determine
      the role of neutrophils in photoageing of human skin. METHODS: Healthy white
      skinned volunteers were recruited and their sun-protected buttock skin was
      exposed to solar-simulated radiation (SSR) in dose-response and time-course
      studies. Punch biopsies were taken and the influx of neutrophils and the
      expression of neutrophil elastase and MMPs was studied using immunohistochemical
      techniques and in situ zymography. RESULTS: Neutrophil elastase and MMPs were
      detected only in skin irradiated with erythemogenic doses (> or = 1 minimal
      erythema doses) of SSR. Immunohistochemical double staining demonstrated
      neutrophils to be the major source of MMP-1, MMP-8 and MMP-9. In situ zymography
      showed elastase, collagenase and gelatinase enzyme activity in those cells.
      CONCLUSIONS: Our study suggests that neutrophils participate in the process of
      photoageing of human skin as they infiltrate the skin and release enzymatically
      active elastase (neutrophil elastase), collagenase (MMP-1) and gelatinase (MMP
      9).

PMID- 15727647
TI  - No compensatory sweating after botulinum toxin treatment of palmar hyperhidrosis.
AB  - BACKGROUND: Primary focal hyperhidrosis is caused by excessive secretion by
      eccrine sweat glands, usually at the palms, soles and axillae. The underlying
      mechanism is unclear. In recent years botulinum toxin A has emerged as a useful
      treatment. Compensatory sweating, which is a major problem in many patients who
      have undergone transthoracic endoscopic sympathectomy for hyperhidrosis, has only
      rarely been reported after botulinum toxin. However, this potential side-effect
      of botulinum toxin treatment has not been systematically examined. OBJECTIVES: To
      investigate if treatment with botulinum toxin A in hyperhidrotic hands may cause
      compensatory sweating at other skin locations. METHODS: In 17 patients with a
      history of palmar hyperhidrosis repeated measurements of evaporation were made
      before and up to 6 months after treatment of the hands with botulinum toxin A.
      Recordings were made at 16 skin areas and compared with subjective estimates of
      sweating. RESULTS: Following treatment, palmar evaporation decreased markedly and
      then returned slowly towards pretreatment values, but was still significantly
      reduced 6 months after treatment. No significant increase of sweating was found
      after treatment in any nontreated skin area. CONCLUSIONS: Successful treatment of
      palmar hyperhidrosis with botulinum toxin does not evoke compensatory
      hyperhidrosis in nontreated skin territories.

PMID- 15727649
TI  - Psychosocial aspects of patients with focal hyperhidrosis. Marked reduction of
      social phobia, anxiety and depression and increased quality of life after
      treatment with botulinum toxin A.
AB  - BACKGROUND: Primary focal hyperhidrosis (PFH) is defined as excessive sweating
      typically localized to specific body areas such as axillae, hands and feet. An
      association between PFH and anxiety as well as depressive syndromes has been
      suggested. OBJECTIVES: To investigate a possible association between PFH and
      anxiety, depression, social phobia and quality of life, and to study the effect
      of treatment with botulinum toxin A on these factors. METHODS: PFH was confirmed
      clinically and by gravimetry. To measure anxiety and depressive syndromes several
      German versions of standardized questionnaires were used: State-Trait Anxiety
      Inventory G Form X2 (STAI), Social Phobia Scale (SPS), Symptom Checklist of
      Derogatis (SCL-90-R), subscales 'Social Insecurity', 'Depression', 'Anxiety' and
      'Phobia', and Hospital Anxiety and Depression Scale (HADS-D). Quality of life was
      assessed using Skindex. Two analyses were performed. The first analysis included
      all patients with PFH, the second analysis only patients with PFH who were
      treated with botulinum toxin A. In the latter group the questionnaires were
      repeated 2-4 weeks after treatment. RESULTS: For the total group at baseline the
      values for STAI, SCL-90-R, HADS-D and SPS were well within the normal range.
      However, in the group of patients treated with botulinum toxin A, the mean +/- SD
      SPS score was 17.6 +/- 15.5, i.e. above the normal range. Quality of life was
      impaired, with a mean +/- SD Skindex score of 24.3 +/- 5.7 at baseline. Treatment
      with botulinum toxin A led to a significant reduction in all investigated
      symptoms. CONCLUSIONS: Despite an impaired quality of life, patients with PFH in
      general do not show increased symptoms of anxiety, depression or social phobia.
      Only in the subgroup of patients treated with botulinum toxin A was the SPS
      increased at baseline. Treatment with botulinum toxin A led to a marked
      improvement in all factors investigated.

PMID- 15727648
TI  - Efficacy and acceptability of a new topical skin lotion of sodium cromoglicate
      (Altoderm) in atopic dermatitis in children aged 2-12 years: a double-blind,
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common inflammatory allergic disease of
      children. The primary anti-inflammatory therapy is topical steroids. An effective
      treatment without the topical and systemic adverse effects of corticosteroids
      would be useful. Topical formulations of sodium cromoglicate have been researched
      in the past, but without consistent results. We report a trial of a new aqueous
      skin lotion of sodium cromoglicate (Altoderm) in children with AD. OBJECTIVES: To
      compare the efficacy, safety and acceptability of Altoderm lotion with a placebo
      control in the treatment of AD in children. METHODS: A double-blind, controlled
      study in which children aged 2-12 years with AD were randomized to 12 weeks of
      treatment with a lotion containing 4% sodium cromoglicate (Altoderm) or the
      lotion base. To be included subjects had to have a SCORAD score of > or = 25 and
      < or = 60 at both of two clinic visits 14 days apart. Subjects continued using
      existing treatment which included emollients and topical steroids. The primary
      outcome was the change in the SCORAD score. The two groups were compared for the
      change in the SCORAD score from the second baseline visit to the visit after 12
      weeks of treatment using an analysis of variance. Secondary outcome measures
      included parents' assessment of symptoms, usage of topical steroids recorded on
      daily diary cards, and final opinions of treatment by parent and clinician.
      Parents were asked about adverse effects at each clinic visit and the responses
      recorded. RESULTS: Fifty-eight children were randomized to Altoderm and 56 to
      placebo and all were included in the intention-to-treat analysis. The mean +/- SD
      SCORAD scores at baseline were 41.0 +/- 9.0 (Altoderm) and 40.4 +/- 8.73
      (placebo). These scores were reduced after 12 weeks by 13.2 (36%) with Altoderm
      and by 7.6 (20%) with placebo. The difference of 5.6 (95% confidence interval 1.0
      10.3) is statistically significant (P = 0.018). Diary card symptoms improved with
      both treatments but the improvement was greater in the Altoderm-treated patients.
      Topical steroid usage was reduced in both groups and was larger in the Altoderm
      treated patients. The differences were statistically significant for the mean of
      all symptoms, the overall skin condition and use of topical steroids. Those for
      itching and sleep loss were not. Treatment-related adverse events were reported
      in 11 subjects (Altoderm seven, placebo four). Most of these referred to
      irritation, redness and burning at the site of application. There were four
      reports of erythema and pruritus (Altoderm three, placebo one), and three reports
      of application site burning (Altoderm two, placebo one). None was reported as
      severe or very severe. CONCLUSIONS: These results show a clinically useful
      benefit of this sodium cromoglicate lotion in children with moderately severe AD.

PMID- 15727650
TI  - CADASIL-an unusual manifestation with prominent cutaneous involvement.
AB  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leucencephalopathy (CADASIL) is a rare vascular disorder affecting mainly the
      central nervous system with transient ischaemic attacks, strokes, psychiatric
      symptoms and dementia. It is a progressive familial disease owing to mutations in
      the Notch3 gene. Clinically apparent skin involvement is usually absent. Electron
      microscopy of seemingly uninvolved skin reveals characteristic granular deposits
      in the basal lamina of vessels and adnexals. We report on a case of CADASIL with
      generalized haemorrhagic macules and patches. Typical neurological symptoms as
      well as classical findings in histopathology and electron microscopy confirmed
      the diagnosis. Immunofluorescence showed an increased number of vessels with
      walls markedly thickened by deposits of fibrin, complement and immunoglobulins.
      This method could serve as an additional method for accurate diagnosis of
      CADASIL.

PMID- 15727651
TI  - Purpuric adult T-cell leukaemia/lymphoma: expansion of unusual CD4/CD8 double
      negative malignant T cells expressing CCR4 but bearing the cytotoxic molecule
      granzyme B.
AB  - A 78-year-old Japanese woman with adult T-cell leukaemia/lymphoma (ATL) presented
      with an unusual purpuric and erythematous eruption on the face and trunk.
      Immunohistochemical and flow cytometric analyses showed that the tumour cells
      were CD4/CD8 double-negative, and expressed CCR4 T-helper (Th) 2 chemokine
      receptors. Despite these features, the cells aberrantly produced granzyme B,
      which is a cytotoxic molecule usually produced by CD8(+) cytotoxic T cells,
      natural killer cells, or occasionally by Th1 cells. In a purpuric lesion,
      extravasation of erythrocytes was associated with an infiltrate of these
      cytotoxic tumour cells. Our case suggests phenotypical and functional
      heterogeneity of tumour cells in ATL, which may be closely related to the
      clinical appearance of the skin eruption.

PMID- 15727652
TI  - A homozygous cathepsin C mutation associated with Haim-Munk syndrome.
AB  - Haim-Munk syndrome (HMS) is a rare autosomal recessive disorder characterized
      clinically by abnormal palmoplantar hyperkeratosis and destruction of the
      periodontium, with hallmarks of onychogryphosis and arachnodactyly. Germline
      mutations in the lysosomal protease cathepsin C gene (CTSC) have been described
      in a single patient with HMS and in several individuals with the clinically
      related disorder Papillon-Lefevre syndrome (PLS). We describe a patient with HMS.
      We have analysed the cathepsin C gene in the proband and her mother. Sequence
      analysis of CTSC in the proband revealed a homozygous mutation at codon 196 (587T
      ->C) within exon 4 that altered the conserved leucine to proline (Leu196Pro),
      whereas the patient's mother was heterozygous for that mutation. The same
      mutation has previously been described in an unrelated Brazilian family with PLS.
      An identical single missense mutation in the cathepsin C gene may underlie both
      PLS and HMS. These findings confirm that HMS and PLS are allelic variants of
      cathepsin C gene mutations and suggest that other factors (environmental or
      genetic) may be important determinants of the clinical phenotype of HMS and PLS.

PMID- 15727653
TI  - Unusual inflammatory and hyperkeratotic halo naevus in children.
AB  - Although the classic halo naevus (HN) is a melanocytic naevus with a surrounding
      rim of depigmentation, these naevi can present unusual features. We describe an
      unusual and previously unreported variety of HN in children. Between March 1999
      and September 2002, 14 children (11 boys and three girls, age range 6-14 years)
      were referred to us for evaluation of one or more 'inflamed' naevi. All the
      affected naevi showed the same clinical development: (i) after an initial
      inflammatory stage their surfaces gradually became thickened and rough, then (ii)
      verrucous and raised, and finally (iii) scaly crusted. A marked halo of
      depigmentation subsequently developed in all lesions, with simultaneous
      disappearance of the hyperkeratotic surface appearance. Lesions were multiple in
      five cases and single in nine, and were mainly located on the back (nine cases).
      Excisional biopsy was performed in eight cases. The biopsies were all taken in
      the 'prehalo phase'. In each case, histopathology revealed a compound melanocytic
      naevus, with additional features that varied depending on the clinical stage of
      the lesion. Immunohistochemical staining of the dense inflammatory infiltrate
      showed a predominance of CD3(+)/CD8(+) T lymphocytes, as usually occurs in HN. On
      the basis of these observations, we believe that the described naevi represent an
      unusual variety of HN in children. Knowledge of this possible clinical evolution
      of HN is important to avoid unnecessary surgical excision in these young
      patients.

PMID- 15727654
TI  - Dermoscopy for early detection of facial lentigo maligna.
AB  - Up until now, only lesions selected on the basis of their clinical atypia or
      which appear equivocal on naked eye examination have been shown to benefit from
      the use of dermoscopy. In our experience, dermoscopic evaluation of lesions
      located on the face may require a different approach, as a histopathological
      diagnosis of malignancy is not uncommon in clinically trivial lesions (i.e.
      lesions lacking the ABCD criteria for clinical suspicion). Moreover, at this site
      dermoscopy reveals specific criteria according to the particular histological
      architecture shown by sun-damaged skin. We report four cases of lentigo maligna
      (LM) of the face whose identification depended on dermoscopic examination which
      was performed routinely on all facial lesions, as the lesions did not show ABCD
      clinical criteria for malignancy. In our experience, the identification of early
      signs of malignancy by dermoscopy may indicate the excision of LM at an early
      phase, before the lesion is associated with the ABCD signs of melanoma.
      Dermatologists should avoid the mistake of immediately excluding a diagnosis of
      malignancy when examining an ABCD-negative pigmented skin lesion of the face.

PMID- 15727655
TI  - An unusual ectodermal dysplasia with unique eye defects.
AB  - We report a 12-year-old boy with dental, auricular, nasolacrimal duct and unique
      eyelid anomalies as well as cribriform scrotal atrophy. We believe this is the
      first description of such a case, although many of the features fit within the
      spectrum of the ankyloblepharon/ectodermal dysplasia/clefting (AEC) syndrome.

PMID- 15727656
TI  - Postinflammatory hyperpigmentation in an Asian patient: a dramatic response to
      oral isotretinoin (13-cis-retinoic acid).

PMID- 15727657
TI  - CD56-negative blastic natural killer-cell lymphoma (agranular CD4(+)/CD56(+)
      haematodermic neoplasm)?

PMID- 15727658
TI  - Erythema multiforme due to progesterone in a low-dose oral contraceptive pill.

PMID- 15727659
TI  - (18)F-fluorodeoxyglucose positron emission tomography detection of eccrine
      porocarcinoma.

PMID- 15727660
TI  - Expression of the cyclin-dependent kinase inhibitor p27(kip-1) in benign naevi
      and correlation with Ki-67 proliferative index.

PMID- 15727661
TI  - Human herpesviruses in bullous pemphigoid lesions.

PMID- 15727662
TI  - Treatment of cutaneous metastatic melanoma with imiquimod 5% cream and the pulsed
      dye laser.

PMID- 15727663
TI  - Pegylated interferon alfa-induced sarcoidosis: two sides of the same coin.

PMID- 15727664
TI  - Apocrine hidrocystoma on the tip of a finger.

PMID- 15727665
TI  - Role of Mycobacterium w vaccine in the management of psoriasis.

PMID- 15727666
TI  - The Self-Administered Psoriasis Area and Severity Index provides an objective
      measure of psoriasis severity.

PMID- 15727668
TI  - In vivo confocal reflectance microscopy for the characterization of melanocytic
      nests and correlation with dermoscopy and histology.

PMID- 15727667
TI  - Topical calcineurin inhibitors in treating Jessner's lymphocytic infiltration of
      the skin: report of a case.

PMID- 15727669
TI  - Successful treatment of a refractory verruca in a child with acute lymphoblastic
      leukaemia with topical cidofovir.

PMID- 15727670
TI  - Fumaric acid esters therapy: a new treatment modality in pityriasis rubra
      pilaris?

PMID- 15727672
TI  - Isolated multiple congenital epithelioid blue naevus.

PMID- 15727671
TI  - Clear reticulated cytoplasm of human eccrine sweat glands: immunohistochemical
      differentiation from pathological degeneration.

PMID- 15727673
TI  - The ubiquitous presence of warts on human skin needs acknowledgement for better
      direction of papillomavirus research.

PMID- 15727674
TI  - Botulinum toxin is helpful in aquagenic palmoplantar keratoderma.

PMID- 15727675
TI  - Digital dermoscopy analysis and internet-based program for discrimination of
      pigmented skin lesion dermoscopic images.

PMID- 15727677
TI  - Progressive linear lichen planus and metastatic carcinoma.

PMID- 15727676
TI  - The use of 1% pimecrolimus cream for the treatment of steroid-induced rosacea.

PMID- 15727678
TI  - A case of idiopathic leuconychia totalis and partialis.

PMID- 15727680
TI  - Can Zipf's law be adapted to normalize microarrays?
AB  - BACKGROUND: Normalization is the process of removing non-biological sources of
      variation between array experiments. Recent investigations of data in gene
      expression databases for varying organisms and tissues have shown that the
      majority of expressed genes exhibit a power-law distribution with an exponent
      close to -1 (i.e. obey Zipf's law). Based on the observation that our single
      channel and two channel microarray data sets also followed a power-law
      distribution, we were motivated to develop a normalization method based on this
      law, and examine how it compares with existing published techniques. A
      computationally simple and intuitively appealing technique based on this
      observation is presented. RESULTS: Using pairwise comparisons using MA plots (log
      ratio vs. log intensity), we compared this novel method to previously published
      normalization techniques, namely global normalization to the mean, the quantile
      method, and a variation on the loess normalization method designed specifically
      for boutique microarrays. Results indicated that, for single channel microarrays,
      the quantile method was superior with regard to eliminating intensity-dependent
      effects (banana curves), but Zipf's law normalization does minimize this effect
      by rotating the data distribution such that the maximal number of data points lie
      on the zero of the log ratio axis. For two channel boutique microarrays, the
      Zipf's law normalizations performed as well as, or better than existing
      techniques. CONCLUSION: Zipf's law normalization is a useful tool where the
      Quantile method cannot be applied, as is the case with microarrays containing
      functionally specific gene sets (boutique arrays).

PMID- 15727681
TI  - Reporting quality of randomized trials in the diet and exercise literature for
      weight loss.
AB  - BACKGROUND: To adequately assess individual studies and synthesize quantitative
      research on weight loss studies, transparent reporting of data is required. The
      authors examined the reporting quality of randomized trials in the weight loss
      literature, focusing exclusively on subject characteristics as they relate to
      enrollment, allocation, and follow-up. METHODS: An extensive literature review,
      which included a computerized search of the MEDLINE database, manual searches of
      bibliographic references, and cross-referencing of 92 review articles was
      conducted. A checklist, based on CONSORT recommendations, was used to collect
      information on whether or not authors reported age, gender, co-morbid disease,
      medication use, race/ethnicity, and postmenopausal status. Also tracked was
      whether or not initial and final sample size was reported and stratified by
      gender. RESULTS: Of 604 possible articles, 231 articles met eligibility criteria.
      Important subject characteristics were not reported as the following breakdown
      indicates: age (11%), gender (4%), race/ethnicity (86%), co-morbid disease states
      (34%), and medication use (92%). Additionally, 21% of articles failed to report
      initial sample size by gender while 69% neglected to report final sample size by
      gender. CONCLUSION: Inadequate reporting can create difficulties with
      interpretation and can lead to biased results receiving false credibility. The
      quality of reporting for weight loss studies needs considerable improvement.

PMID- 15727683
TI  - Individual patient data meta-analysis : Cervical stitch (cerclage) for preventing
      pregnancy loss in women.
AB  - BACKGROUND: Cervical cerclage is a surgical procedure involving suturing the
      cervix with a purse type stitch to keep it closed during pregnancy. This
      procedure has been used widely in the management of pregnancies considered at
      high risk of preterm delivery. Several observational studies into the efficacy of
      cervical cerclage have claimed high rates of successful pregnancy outcome in
      women with a poor obstetric history attributed to cervical incompetence. However,
      a recent aggregate data Cochrane review found no such conclusive evidence from
      seven included randomised studies. Current data suggests that cervical cerclage
      is likely to benefit women considered to be 'at very high risk' of a second
      trimester miscarriage due to a cervical factor, however identifying such women
      remains elusive and many women may be treated unnecessarily. Undertaking an
      individual patient data (IPD) meta-analysis of the studies will allow us to
      investigate whether treatment is more effective in particular subgroups. Such an
      analysis will also provide a more powerful analysis of the predictors of preterm
      delivery and pregnancy loss, including ultrasound measurement of cervical length,
      and will allow a more complete analysis of 'time to event' outcomes.
      METHODS/DESIGN: The analysis will include data from randomised trials comparing
      the intervention of elective cerclage versus no cerclage or bedrest to prevent
      miscarriage or pre-term labour. A specific list of data will be requested for
      each trial, including demographic and obstetric history data. The primary
      outcomes of interest will be neonatal mortality/morbidity. Attention will also be
      given to secondary outcomes such as time from randomisation to delivery, preterm
      delivery before 32 weeks and maternal morbidity. An intention to treat analysis
      will be performed, with attention paid to assessing clinical and statistical
      heterogeneity. Multilevel models with patients and trials as the two levels will
      be explored to investigate treatment effect on various outcomes. Patient-level
      covariates will be incorporated into the models in an attempt to account for
      statistical heterogeneity as well as to investigate interactions with treatment
      effect. DISCUSSION: Predictive models generated from our analysis should lead to
      more effective counselling of women at risk and a more cost effective use of
      cerclage.

PMID- 15727682
TI  - One year soy protein supplementation has positive effects on bone formation
      markers but not bone density in postmenopausal women.
AB  - BACKGROUND: Although soy protein and its isoflavones have been reported to reduce
      the risk of osteoporosis in peri- and post-menopausal women, most of these
      studies are of short duration (i.e. six months). The objective of this study was
      to examine if one year consumption of soy-containing foods (providing 25 g
      protein and 60 mg isoflavones) exerts beneficial effects on bone in
      postmenopausal women. METHODS: Eighty-seven eligible postmenopausal women were
      randomly assigned to consume soy or control foods daily for one year. Bone
      mineral density (BMD) and bone mineral content (BMC) of the whole body, lumbar
      (L1-L4), and total hip were measured using dual energy x-ray absorptiometry at
      baseline and after one year. Blood and urine markers of bone metabolism were also
      assessed. RESULTS AND DISCUSSION: Sixty-two subjects completed the one-year long
      study. Whole body and lumbar BMD and BMC were significantly decreased in both the
      soy and control groups. However, there were no significant changes in total hip
      BMD and BMC irrespective of treatment. Both treatments positively affected
      markers of bone formation as indicated by increased serum bone-specific alkaline
      phosphatase (BSAP) activity, insulin-like growth factor-I (IGF-I), and
      osteocalcin (BSAP: 27.8 and 25.8%, IGF-I: 12.8 and 26.3%, osteocalcin: 95.2 and
      103.4% for control and soy groups, respectively). Neither of the protein
      supplements had any effect on urinary deoxypyridinoline excretion, a marker of
      bone resorption. CONCLUSION: Our findings suggest that although one year
      supplementation of 25 g protein per se positively modulated markers of bone
      formation, this amount of protein was unable to prevent lumbar and whole body
      bone loss in postmenopausal women.

PMID- 15727684
TI  - Synergistic inhibition of human cytomegalovirus replication by interferon
      alpha/beta and interferon-gamma.
AB  - BACKGROUND: Recent studies have shown that gamma interferon (IFN-gamma)
      synergizes with the innate IFNs (IFN-alpha and IFN-beta) to inhibit herpes
      simplex virus type 1 (HSV-1) replication in vitro. To determine whether this
      phenomenon is shared by other herpesviruses, we investigated the effects of IFNs
      on human cytomegalovirus (HCMV) replication. RESULTS: We have found that as with
      HSV-1, IFN-gamma synergizes with the innate IFNs (IFN-alpha/beta) to potently
      inhibit HCMV replication in vitro. While pre-treatment of human foreskin
      fibroblasts (HFFs) with IFN-alpha, IFN-beta or IFN-gamma alone inhibited HCMV
      plaque formation by approximately 30 to 40-fold, treatment with IFN-alpha and IFN
      gamma or IFN-beta and IFN-gamma inhibited HCMV plaque formation by 163- and 662
      fold, respectively. The generation of isobole plots verified that the observed
      inhibition of HCMV plaque formation and replication in HFFs by IFN-alpha/beta and
      IFN-gamma was a synergistic interaction. Additionally, real-time PCR analyses of
      the HCMV immediate early (IE) genes (IE1 and IE2) revealed that IE mRNA
      expression was profoundly decreased in cells stimulated with IFN-alpha/beta and
      IFN-gamma (approximately 5-11-fold) as compared to vehicle-treated cells.
      Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE
      protein expression, as demonstrated by western blotting and immunofluorescence.
      CONCLUSION: These findings suggest that IFN-alpha/beta and IFN-gamma
      synergistically inhibit HCMV replication through a mechanism that may involve the
      regulation of IE gene expression. We hypothesize that IFN-gamma produced by
      activated cells of the adaptive immune response may potentially synergize with
      endogenous type I IFNs to inhibit HCMV dissemination in vivo.

PMID- 15727685
TI  - Mutational study of sapovirus expression in insect cells.
AB  - Human sapovirus (SaV), an agent of human gastroenteritis, cannot be grown in cell
      culture, but expression of the recombinant capsid protein (rVP1) in a baculovirus
      expression system results in the formation of virus-like particles (VLPs). In
      this study we compared the time-course expression of two different SaV rVP1
      constructs. One construct had the native sequence (Wt construct), whereas the
      other had two nucleotide point mutations in which one mutation caused an amino
      acid substitution and one was silent (MEG-1076 construct). While both constructs
      formed VLPs morphologically similar to native SaV, Northern blot analysis
      indicated that the MEG-1076 rVP1 mRNA had increased steady-state levels.
      Furthermore, Western blot analysis and an antigen enzyme-linked immunosorbent
      assay showed that the MEG-1076 construct had increased expression levels of rVP1
      and yields of VLPs. Interestingly, the position of the mutated residue was
      strictly conserved residue among other human SaV strains, suggesting an important
      role for rVP1 expression.

PMID- 15727686
TI  - Abdominal fat and hip fracture risk in the elderly: the Dubbo Osteoporosis
      Epidemiology Study.
AB  - BACKGROUND: Fat mass, which is a major component of body weight, is directly
      related to bone mineral density and reduced fracture risk. It is not known
      whether abdominal fat is associated with hip fracture. The present study was
      designed to examine the association between abdominal fat and hip fracture in
      women and men aged 60+ years. METHODS: This was a nested case-control study with
      one fracture case being matched with two controls of the same age. In women 63
      cases were matched with 126 controls, and in men 26 cases were matched with 52
      controls. Hip fracture was confirmed by X-ray and personal interview. Other
      measurements included weight, height, body mass index (BMI), abdominal fat, and
      femoral neck bone density (FNBMD). Conditional logistic regression model was used
      to analyse data. RESULTS: The odds ratio of hip fracture risk associated with
      each 10% lower abdominal fat was 1.5 (95% CI, 1.1 to 2.1) in women and 1.2 (95%
      CI, 0.7 to 2.0) in men. However after adjusting for FNBMD or body weight, the
      abdominal fat-fracture association was no longer statistically significant.
      Similarly, body weight and BMI was each significantly associated with hip
      fracture risk (in women), but after taking with account the effect of FNBMD, the
      association become statistically non-significant. CONCLUSION: Lower abdominal fat
      was associated with an increased risk of hip fracture in elderly women, but the
      association was not independent of FNBMD or weight. The contribution of abdominal
      fat to hip fracture risk is likely to be modest.

PMID- 15727688
TI  - [Glucotoxicity, lipotoxicity and the nonalcoholic fatty liver disease].

PMID- 15727687
TI  - Monitoring the initial pulmonary absorption of two different beclomethasone
      dipropionate aerosols employing a human lung reperfusion model.
AB  - BACKGROUND: The pulmonary residence time of inhaled glucocorticoids as well as
      their rate and extend of absorption into systemic circulation are important
      facets of their efficacy-safety profile. We evaluated a novel approach to
      elucidate the pulmonary absorption of an inhaled glucocorticoid. Our objective
      was to monitor and compare the combined process of drug particle dissolution, pro
      drug activation and time course of initial distribution from human lung tissue
      into plasma for two different glucocorticoid formulations. METHODS: We chose
      beclomethasone dipropionate (BDP) delivered by two different commercially
      available HFA-propelled metered dose inhalers (Sanasthmax/Becloforte and
      Ventolair/Qvar). Initially we developed a simple dialysis model to assess the
      transfer of BDP and its active metabolite from human lung homogenate into human
      plasma. In a novel experimental setting we then administered the aerosols into
      the bronchus of an extracorporally ventilated and reperfused human lung lobe and
      monitored the concentrations of BDP and its metabolites in the reperfusion fluid.
      RESULTS: Unexpectedly, we observed differences between the two aerosol
      formulations Sanasthmax/Becloforte and Ventolair/Qvar in both the dialysis as
      well as in the human reperfusion model. The HFA-BDP formulated as Ventolair/Qvar
      displayed a more rapid release from lung tissue compared to
      Sanasthmax/Becloforte. We succeeded to explain and illustrate the observed
      differences between the two aerosols with their unique particle topology and
      divergent dissolution behaviour in human bronchial fluid. CONCLUSION: We conclude
      that though the ultrafine particles of Ventolair/Qvar are beneficial for high
      lung deposition, they also yield a less desired more rapid systemic drug
      delivery. While the differences between Sanasthmax/Becloforte and Ventolair/Qvar
      were obvious in both the dialysis and lung perfusion experiments, the latter
      allowed to record time courses of pro-drug activation and distribution that were
      more consistent with results of comparable clinical trials. Thus, the
      extracorporally reperfused and ventilated human lung is a highly valuable
      physiological model to explore the lung pharmacokinetics of inhaled drugs.

PMID- 15727689
TI  - [Epidemiological survey of prevalence of fatty liver and its risk factors in a
      general adult population of Shanghai].
AB  - OBJECTIVE: To investigate the prevalence and major risk factors of fatty liver
      among adult residents in Shanghai. METHODS: A cross-sectional survey with
      multiple-stage stratified cluster and random sampling was performed. All
      residents aged 16 and above were invited to participate in the survey; they came
      from four communities of Yangpu District and Pudong New District. Questionnaire,
      physical examination, serum lipid-profile, and 75 gram oral glucose tolerance
      test and ultrasonographic examination of liver were undertaken. Analysis of data
      was performed through SPSS 11.0 for Windows statistical package. RESULTS: A total
      of 3175 residents took part in the survey, which was 75% of adult residents of
      the investigated communities and 2.26/10 000 of Shanghai municipal residents. Of
      the 3175, 1218 were males and 1957 were females. The mean age of the participants
      was 52.4+/-15.1 years and ranged from 16 to 88 years. Fatty liver was detected
      with ultrasound examination in 661 participants (20.82%), among which 3.48% had
      alcoholic fatty liver, 4.08% had suspected alcoholic fatty liver, and 92.43% had
      nonalcoholic fatty liver. The age-adjusted, sex-adjusted prevalence of fatty
      liver in Shanghai adult residents was 17.29%, the prevalence of alcoholic fatty
      liver, suspicious alcoholic fatty liver, and nonalcoholic fatty liver in Shanghai
      adult residents were 0.79%, 1.15%, and 15.35%, respectively. The prevalence of
      fatty liver was increased with aging in males and in females. Among participants
      younger than 50 years old, the prevalence of fatty liver in males was
      significantly higher than that in females, but in participants older than 50
      years the case was just the opposite, higher in females. The mean age (years),
      body mass index (BMI), waist circumference, blood pressure, fasting and two hour
      serum glucose level, triglyceride (TG), total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), and the presence of obesity, diabetes mellitus,
      hypertension, dyslipidemia, and gallstones in the fatty liver group was
      significantly higher than those in the group without fatty liver, but the high
      density lipoprotein cholesterol (HDL-C) level and the educational level were both
      lower in the fatty liver group. Logistic regression analysis demonstrated that
      the prevalence of fatty liver was only positively correlated to nine risk
      factors, including male sex, educational level, waist circumference, BMI, fasting
      glucose level, HDL-C, TG, hypertension and diabetes mellitus. In heavy drinkers,
      obesity increased the risk for fatty liver by 4.8-fold, but heavy drinking only
      increased the risk for fatty liver 1.5-fold (95% CI 0.9-2.6, P=0.1685).
      CONCLUSION: There is a high prevalence of fatty liver among adult residents in
      Shanghai, and nonalcoholic fatty liver is the major type. Metabolic disorders
      such as obesity and diabetes mellitus, hypertension and hyperlipidemia are more
      closely associated with fatty liver than heavy drinking in Shanghai.

PMID- 15727690
TI  - [Effect of Endotoxin on the expression of peroxisome proliferator-activated
      receptor alpha in the development of nonalcoholic steatohepatitis in rats].
AB  - OBJECTIVE: To study the effect of endotoxin on the expression of peroxisome
      proliferator-activated receptor alpha (PPARa) in the development of nonalcoholic
      steatohepatitis in rats. METHODS: A model of nonalcoholic steatohepatitis (NASH)
      was developed with Wistar rats fed a chow containing 20% maize oil for 14 weeks.
      The endotoxin group rats were intraperitoneally injected with lipopolysaccharide
      (LPS, 1 g/L, 3.0 ml/kg) once 4 hours before the end of the experiment. The
      concentrations of lipids, endotoxin, tumor necrosis factor-a, malondialdehyde,
      free fatty acid in plasma and hepatic tissues were determined and the degree of
      hepatocytic steatosis was studied. The expression of PPARa mRNA in hepatic
      tissues was measured using reverse transcriptase-polymerase chain reaction (RT
      PCR). RESULTS: The expression of PPARa mRNA in the hepatic tissue of the LPS
      group was downregulated markedly in comparison to that of the control group. The
      level of free fatty acid and endotoxin by secreting tumor necrosis factor-a
      increased and triglyceride accumulated in the liver caused malondialdehyde
      content to increase, then lipid peroxidation process enhanced and ALT activity
      increased. Thus, hepatic injury and inflammatory reaction could be accelerated.
      CONCLUSION: Endotoxemia can enhance hepatocellular steatosis and lead to NASH due
      to its downregulating the expression of PPARa mRNA.

PMID- 15727691
TI  - [Diisopropylamine dichloroacetate in the treatment of nonalcoholic fatty liver
      disease: a multicenter random double-blind controlled trial].
AB  - OBJECTIVE: To investigate the efficacy and safety of diisopropylamine
      dichloroacetate in the treatment of nonalcoholic fatty liver diseases (NAFLD).
      METHODS: A randomized, double-blind, dose-paralleled control trial was carried
      out with NAFLD patients. The patients were randomly assigned to 2 groups treated
      with either a high dosage (120 mg/d) or a low dosage (60 mg/d) of
      diisopropylamine dichloroacetate for 8 weeks and the efficacy and safety of the
      drug were examined. RESULTS: 127 cases were recruited for the trial, 63 in the
      high dosage group, and 64 in the low dosage group. No case dropped out in the
      trial but four cases were eliminated (4/127, 3.1%). The final number in this
      trial was 123, with 61 in the high dosage group and 62 in the low dosage group.
      After 8 weeks of treatment, the overall improvement of clinical symptoms in the
      high dosage and in the low dosage group was 87.8% and 79.6%, respectively. ALT
      normalization was found in 55.7% and 69.4% of the cases in the two groups, serum
      lipids were lowered in 67.2% and 67.7% and ultrasound grading of the liver
      alteration severity was lowered in 51.7% and 43.5% in the two groups. The
      differences found between the two groups were of no statistical significance. One
      case from each group was found having an adverse drug reaction of dryness of the
      mouth (1.6%). No severe adverse drug reactions were found. CONCLUSION:
      Diisopropylamine dichloroacetate could be used as a safe and effective drug in
      the treatment of nonalcoholic fatty liver diseases.

PMID- 15727692
TI  - [Comparision of the serotypes and genotypes of hepatitis B virus among HBsAg
      positive hepatitis B patients in a northern city and a southern city of China].

PMID- 15727693
TI  - [Relationship between NF-kappa B binding activity and expression of PPAR gamma
      mRNA in the livers of rats with fatty liver disease].
AB  - OBJECTIVE: To investigate the changes of NF-kappa B binding activity, the
      expression of PPARr and their correlation in the liver of rats with fatty liver
      disease (FLD) induced by different pathogenic factors and to investigate the
      molecular mechanism of the inflammation in FLD. METHODS: 40 Wistar rats were
      randomly divided into 4 groups of ten each: normal group, alcohol group, fat-rich
      diet group, alcohol adding fat-rich diet group. The rats were sacrificed at the
      end of the 16th week from the starting day of the experiment. Serum and liver
      specimens were collected. Histological specimens were stained with HE, SudanIV,
      and Masson and then studied microscopically. The ultrastructural changes were
      also checked under an electron microscope. NF-kappa B binding activity and the
      expression of PPARr mRNA were determined by electrophoretic mobility shift assay
      (EMSA) and RT-PCR respectively. The correlations between NF-kappa B binding
      activity and the expression of PPARr and the biochemical indexes were analyzed.
      RESULTS: Steatosis, inflammation, necrosis and fibrosis were present in livers of
      the rats of all the experimental groups, and were most severe in the alcohol
      adding fat-rich diet group. NF-kappa B binding activity was markedly increased in
      the livers of the alcohol group (142+/-16.32) and of the alcohol adding fat-rich
      diet group (238+/-19.14) in comparison to the livers of the normal (73+/-9.24, F
      = 6.36, 17.93) and those of the fat-rich diet group (84+/-10.38, F = 5.96,
      16.20). Binding activity was higher in the alcohol adding fat-rich diet group
      than that in the simple alcohol group, but there was no difference between those
      of the fat-rich diet and normal groups. The level of PPARr mRNA was lower in the
      livers of the alcohol, fat-rich diet, alcohol adding fat-rich diet groups
      (0.2530+/-0.069, 0.3647+/-0.082, 0.1226+/-0.054) than that of the controls
      (0.8097+/-0.094) (F = 15.43, 7.24, 21.45). NF-kappa B binding activity was
      correlated positively with the level of serum TNF alpha (r = 0.527, 0.639) and
      the content of MDA in the liver homogenates (r = 0.723, 0.537), but negatively
      with the expression of PPARr in the livers of the alcohol and the alcohol adding
      fat-rich diet groups (r = -0.568, -0.891). CONCLUSION: The enhanced nuclear
      factors NF-kappa B binding activity and decreased expression of PPARr play a
      pivotal role in the inflammatory response of FLD induced by alcohol and fat-rich
      diet. It may provide a new idea for treating FLD effectively.

PMID- 15727694
TI  - [Study on therapeutic effects of metformin on rat fatty livers induced by high
      fat feeding].
AB  - OBJECTIVES: To explore the therapeutic effects of metformin on rat fatty livers
      induced by high fat feeding. METHODS: A fatty liver model was established by
      feeding rats with a high caloric laboratory chow for 12 weeks, then the rats were
      randomly divided into three groups, i.e. model control group, metformin group and
      dietary treatment group. A normal control group was organized at the same time.
      The rats of the metformin group were given metformin 156 mg/kg/d while the other
      groups were given distilled water of the same volume by stomach feeding. The
      model control group rats were fed with high caloric laboratory chow while other
      groups were fed a normal diet. After four weeks, all the animals were sacrificed.
      Liver index (liver/body weight ratio), serum activities of liver-associated
      enzymes, blood lipids, liver triglycerides, fasting blood glucose, fasting plasma
      insulin, HOMA insulin resistance index (HOMA-IR), and the liver histology of rats
      of all groups were assayed. RESULTS: The body weight, liver index, serum
      activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total cholesterol
      (TC), triglycerides (TG) and liver triglycerides in the model group increased
      significantly, while HDL-cholesterol concentration decreased significantly.
      Fasting blood glucose, fasting plasma insulin and HOMA-IR showed an increasing
      tendency, but there was no significant difference of those indexes among the
      three groups. The liver histology in the model group showed moderate to severe
      steatosis, mainly as macro vesicle steatosis, lobular inflammatory, cell
      infiltration and necrosis. Compared with the model group, the levels of body
      weight, liver index, serum ALT, ALP, TC, TG and liver triglycerides in the
      metformin group were significantly lower and were similar to those of the normal
      group, while their HDL-cholesterol concentration was significantly higher. The
      liver histology in the metformin group was nearly normal. In the dietary
      treatment group, hyperlipidemia persisted, although liver index and GGT were
      lower and the liver histology changes were somewhat milder. CONCLUSION: It is
      suggestive that metformin might be effective in treating rat fatty liver induced
      by high fat feeding.

PMID- 15727695
TI  - [Establishing a rat insulin-resistant fatty liver model].
AB  - OBJECTIVE: To create a rat insulin resistant fatty liver model. METHODS: 14 male
      Wistar rats were randomly divided into a model and a control group. The model
      rats were fed a high-fat diet (45% of energy from fat) for 8 weeks, and the
      control group a standard diet (19% of energy from fat). Insulin sensitivity was
      measured with glucose infusion rate (GIR) by the euglycermic hyperinsulinemia
      clamp technique. The aminotransferase, triglyceride (TG), free fatty acid (FFA),
      superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by biochemical
      methods, and insulin was measured by radioimmunoassay. The histological and
      ultrastructural changes of all rat livers were scored using light and electron
      microscopy. RESULTS: Rats fed the high-fat diet developed panlobular
      macrovesicular steatosis, lobular inflammatory cell infiltration and abnormal
      mitochondria, whereas those fed the standard diet had normal livers. All model
      group rats had elevated levels of aminotransferase, TG, FFA, insulin and liver
      index, and low GIR. In addition, the high-fat diet increased MDA and decreased
      SOD. CONCLUSION: A fatty liver and insulin resistance model was successfully
      developed in rats fed a high-fat diet for 8 weeks, which provided a useful
      experimental tool for elucidating pathogenesis and treatment of fatty liver.

PMID- 15727696
TI  - [Distribution of hepatitis B virus genotypes in Hubei province and its clinical
      significance].
AB  - OBJECTIVE: To investigate the distribution of hepatitis B virus genotype in Hubei
      province (China) and its clinical significance. METHODS: Serum samples from 190
      HBV DNA positive patients with chronic HBV infection,including 52 asymptomatic
      HBV carriers (ASC), 56 chronic hepatitis (CH), 32 fulminant hepatic failure
      (FHF), 22 liver cirrhosis (LC), and 28 hepatocellular carcinoma (HCC) patients
      were collected and tested for HBV genotypes by type-specific primers. RESULTS: A
      simple and precise genotyping system based on PCR using type-specific primers was
      developed for the determination of genotypes of hepatitis B virus (HBV). Of the
      190 patients, 140 (73.7%) were genotype B and 42 (22.1%) were genotype C.
      Genotype B was more prevalent in the FHF and HCC patients than in the ASC
      patients; the ALT value was significantly higher in genotype B than in genotype C
      patients. The rate of anti-HBe was significantly higher in genotype B than in
      genotype C except in the patients of the ASC group. CONCLUSION: The system we
      used seems to be a useful tool for the molecular diagnosis of HBV infection and
      for large-scale surveys. Genotype B, genotype C and BC combination exist in Hubei
      province, and genotype B is the major genotype in this area especially in FHF and
      HCC patients.

PMID- 15727698
TI  - [Evaluation of the value of ultrasonography in diagnosis of liver fibrosis in
      patients with chronic viral hepatitis].
AB  - OBJECTIVE: It is important to use noninvasive methods to differentiate liver
      fibrosis and liver cirrhosis. A prospective study was conducted to evaluate the
      validity of ultrasonography (US) in evaluating the severity of liver fibrosis in
      patients with chronic viral hepatitis in reference to the pathologic diagnosis of
      their liver biopsy specimens. METHODS: The liver fibrosis status of 324 chronic
      viral hepatitis patients was evaluated by both needle biopsy and US.
      Histologically their liver fibrosis was graded as S0-S4, and the inflammatory
      reaction in the liver was graded as G1-G4. The US examination included
      qualitative description of the liver surface and liver parenchyma, and the
      quantitative parameters were vascular diameters, blood flow volume and spleen
      size. RESULTS: US qualitative description of the liver surface and liver
      parenchyma was correlated to the severity of fibrosis and the degree of the
      inflammation seen in the liver biopsies. An analysis of US quantitative
      parameters showed that a cut-off value of 12.1 cm for the length of spleen had a
      sensitivity of 60.0%, and specificity of 75.3% in detecting early liver fibrosis.
      For other quantitative parameters, the cut-off values were 8mm for the diameter
      of the splenic vein, 30.5 cm/sec for maximal blood flow velocity in the portal
      vein and 12 mm in diameter of the main portal vein. The diagnostic sensitivities
      for these parameters were 60.0%, 78.6% and 76.7%; the diagnostic specificities
      were 78.1%, 66.9% and 44.6% respectively. CONCLUSION: Early cirrhosis can be
      detected by US, and the sonographic results were well paralleled with their
      pathologic diagnoses made by liver biopsies. Individual US parameter has limited
      sensitivity and specificity in diagnosing early cirrhosis. In clinical practice a
      combination of 2-3 parameters could be used to detect or exclude severe liver
      fibrosis.

PMID- 15727697
TI  - [Effects of portaazygous disconnection, portocaval shunt and selective shunts on
      experimental rat liver cirrhosis].
AB  - OBJECTIVE: To evaluate the effects of portaazygous disconnection (PAD),
      portacaval shunt (PCS) and distal splenocaval shunt (DSCS) on the portosytemic
      shunting (PSS), hepatic function (HF), hepatic mitochondrial respiratory function
      (HMRF), oral glucose tolerance test (OGTT) and arterial ketone body ratio (KBR)
      in order to provide a sound basis for selecting suitable operations for patients.
      METHODS: Using a cirrhotic portal hypertensive model induced by CCl4/ethanol in
      Wistar rats, the PSS, HF, HMRF, OGTT and KBR were determined three weeks after
      PCS, DSCS and PAD. RESULTS: It was revealed that: (1) In the cirrhotic portal
      hypertension rats, the PSS increased significantly, HMRF and hepatic reserve
      function (HRF) decreased significantly when compared with the control rats. (2)
      At the time of first postoperative week, the mean blood glucose value in the 120
      minute OGTT in each PAD, PCS and DSCS groups had significant differences compared
      with the cirrhotic control group. But during the second and third postoperative
      weeks, the mean blood glucose values in the 120-minute OGTT in both PAD and DSCS
      groups had no significant differences compared with the cirrhotic control group
      except for the PCS group. The values of KBR in the three operative groups
      decreased significantly compared with the cirrhotic control group during the two
      postoperative weeks. In the third postoperative week, only the values of KBR in
      the PCS group had a significant difference compared with the cirrhotic control
      group. (3) After PCS, the PSS was further increased; HF and HMRF were
      significantly decreased. Little improvement was found in the third postoperative
      week. (4) After DSCS and PAD, the above mentioned indices were less influenced,
      and they were restored more quickly than those in the PCS group. CONCLUSION: We
      found that PAD and DSCS are more desirable than PCS.

PMID- 15727699
TI  - [A report of acute hepatitis E with immunologic hemolysis].

PMID- 15727701
TI  - [Effect of tea polyphenols on alcoholic liver injury].
AB  - OBJECTIVE: To reproduce an experimental model of alcoholic liver disease in rats
      and to investigate the preventive and treatment effects of tea polyphenols on
      alcoholic liver disease. METHODS: 68 male Sprague-Dawley rats were randomly
      divided into 3 groups: alcohol group (gastrically infused with 56% of ethanol
      once a day with a dose of 7 g/kg body weight for 4, 12 and 24 weeks), tea
      polyphenols group (gastric infusion with alcohol same as in the alcohol group and
      with tea polyphenols at 0.25 g/kg bw) and control group (gastric infusion with
      normal saline). At the end of 4, 12 and 24 weeks, blood samples were collected
      and then the rats were sacrificed. Liver samples were obtained for routine
      histological examination and the degree of hepatic steatosis and alcoholic
      hepatitis were examined. Blood specimens were used for evaluation of alanine
      transaminase (ALT) and aspartate aminotransferase (AST). RESULTS: (1) The levels
      of the two transaminases were elevated with the increase of the duration of
      ethanol feeding and the difference is significant. TP significantly mitigated the
      increase of ALT and AST activities induced by the alcohol. (2) Histological
      changes of the liver injury indicated that piecemeal or focal necrosis of
      hepatocytes was present in the centrilobular area. As fibrosis advanced, broader
      septa were formed with central-central and centra-portal bridging necrosis. In
      the TP infusion group, the severity of the pathological changes was significantly
      milder. CONCLUSION: The results of this study revealed that TP mitigated the
      development of alcoholic liver disease, and TP may be a potential drug for
      treatment of alcoholic liver disease.

PMID- 15727700
TI  - [Preparation and identification of hammerhead ribozyme in vitro against caspase
      12 mRNA fragments].
AB  - OBJECTIVE: To design and synthesize ribozymes targeting 138 and 218 sites of the
      mRNA nucleotide of mouse caspase-12, a key intermedium of ER stress mediated
      apoptosis, and to identify their activities through in vitro transcription and
      cleavage. METHODS: The mouse caspase-12 gene fragment was obtained by RT-PCR and
      cloned into the PGEM-T vector under the control of T7 RNA polymerase promoter.
      The transcription product of the target was labeled with a-32P UTP, while
      ribozymes were not labeled. Ribozyme and target RNA were incubated for 90 min at
      37 degree C in a reaction buffer to perform the cleavage reaction. RESULTS: It
      was found that under a condition of 37 degree C, pH 7.5 and with Mg2+ in a
      concentration of 10 mmol/L, Rz138 and Rz218 both cleaved targets at predicted
      sites, and the cleavage efficiency of Rz138 was 100%. CONCLUSION: Rz138 and Rz218
      prepared in vitro possess the perfect specific catalytic cleavage activity. Rz138
      has excellent cleavage efficiency. It may be a promising tool to prevent ER
      stress induced apoptosis through catalytic cleavage of caspase-12 mRNA in vivo.
      It also can be used to verify whether caspase-12 is necessary in ER stress
      induced apoptosis.

PMID- 15727702
TI  - [A discussion of standardization for prothrombin time in patients with advanced
      liver diseases].
AB  - OBJECTIVE: To determine which expression mode of prothrombin time (PT) might
      achieve PT standardization in patients with advanced liver diseases. METHODS: PT
      was measured with six thromboplastins with different ISI values in 16 severe
      chronic hepatitis patients, 50 decompensated liver cirrhosis patients and 30
      patients on oral anticoagulation therapy. The results were expressed in PT
      (second), PTA (%), PTR and INR. RESULTS: In chronic hepatitis patients, the means
      of the six group's PTAs ranged from 24% to 34%, while their upper limits ranged
      from 47% to 61%. The means of the INRs ranged from 2.55 to 5.13, while their
      upper limits ranged from 4.65 to 12.77. Through one-way ANOVA of repeated
      measures, PPTA (0.489) was > PINR (0.120). In patients with liver cirrhosis, the
      means of the PTA in six groups ranged from 50% to 59%, while their upper limits
      ranged from 82% to 90%. The means of the INR ranged from 1.40 to 1.80, while
      their upper limits ranged from 1.97 to 3.69. Through one-way ANOVA of repeated
      measures, PPTA (0.102) was > PINR (0.01). In patients on oral coagulation
      therapy, the means of PTA ranged from 26% to 37%, while their upper limits ranged
      from 39% to 49%. The means of INR ranged from 2.35 to 2.66, while their upper
      limits ranged from 3.16 to 4.26. Through one-way ANOVA of repeated measures, PPTA
      (0.01) was less than PINR (0.102). The correlation between the results detected
      by Neoplastine and by other reagents were analyzed. They correlated well with
      each other when PTA was used as the expression mode of PT in patients with
      advanced liver disease. But in patients on oral anticoagulation therapy, when
      only the INR was used as the expression mode of PT, the correlation was well with
      each other. CONCLUSION: The use of INR provides inadequate standardization. Only
      when the PT is expressed in PTA, then it may provide a standardization mode in
      patients with advanced liver diseases.

PMID- 15727704
TI  - [Current therapeutic strategy of fatty liver diseases].

PMID- 15727703
TI  - [Molecular mechanisms of the protection of SNMC in HepG2 cell apoptosis].
AB  - OBJECTIVE: Apoptosis of the cells of liver cancer cell line HepG2 could be
      induced by TNF alpha and actinomycin D (Act D). In the current study, the
      molecular mechanism of the apoptosis protection of stronger neo-minophagen C
      (SNMC) to HepG2 cells was investigated. METHODS: SNMC was added to the HepG2 cell
      culture medium when the cell concentration reached 0, 2, 20, 100, 200, 800
      microg/ml 30 min before their apoptosis were inducted with TNF alpha and Act D. A
      flow cytometry assay was performed to detect the cell apoptosis rate;
      electromicroscopy was employed to visualize the subcellular structure after
      apoptosis. DNA ladder formation was checked with genomic DNA agarose
      electrophoresis. The expression pattern of apoptosis related protein Caspase-3,
      Bcl-2 and Bax was detected by Western blot. RESULTS: After pretreatment with
      various concentrations of SNMC and 12 hours after treatment with TNF alpha and
      Act D, the HepG2 cell apoptosis rate and DNA ladder formation decreased
      dramatically when the SNMC concentration was higher in the media; the
      intracellular inactive form of Caspase-3 increased while the 17*10(3) active
      Caspase-3 decreased gradually. In addition, the expression of Bcl-2 increased and
      the expression of Bax decreased. Under the electromicroscope, the typical
      nucleolus condensation of HepG2 induced by TNF alpha and Act D was not seen among
      the 100 microg/ml SNMC treated cells. CONCLUSION: SNMC inhibits TNF alpha and Act
      D induced HepG2 cell apoptosis. This protective action may be regulated by
      intracellular apoptosis related factors.

PMID- 15727705
TI  - [Treatment of nonalcoholic fatty liver disease: behavior modification, diet
      therapy and exercise programs].

PMID- 15727706
TI  - [Drug therapy for nonalcoholic fatty liver disease].

PMID- 15727707
TI  - [Abstinence and fatty liver].

PMID- 15727708
TI  - [Evaluation of treatments for nonalcoholic fatty liver disease].

PMID- 15727709
TI  - [The level of serum thrombopoietin in patients with chronic hepatic diseases
      suffering from thrombocytopenia].

PMID- 15727710
TI  - [The application of Bletilla striata in the interventional therapy of
      hepatocellular carcinoma: a comparative study using ACI rats].

PMID- 15727711
TI  - [Pexoxisome proliferator-activated receptor gamma ligands suppress liver
      carcinogenesis induced by diethylnitrosamine in rats].

PMID- 15727712
TI  - [Expression and significance of erb-B receptor family in hepatocellular
      carcinoma].

PMID- 15727713
TI  - [HCV core protein effects on the expression of mutation p53 and Bcl-2 protein in
      HCV hepatitis and cirrhosis].

PMID- 15727714
TI  - [Effect of angiotensin II on NF-kappa B activity and expression of PDGF-BB, TGF
      beta 1 and COX-2 in Kupffer's cells].

PMID- 15727715
TI  - [Expression of subtypes of somatostatin receptors in rat hepatic stellate cells].

PMID- 15727716
TI  - [Effect of hepatocyte cytochrome P450 2E1 gene and its expression in nonalcoholic
      steatosis in rats].

PMID- 15727717
TI  - [Apoptosis of rat hepatic stellate cells induced by Panax notoginseng saponins].

PMID- 15727718
TI  - [Subgenomic replicon model of hepatitis C virus and it's application].

PMID- 15727719
TI  - The cost effectiveness of cardiovascular medicines.

PMID- 15727720
TI  - Intensive versus moderate lipid lowering with statins in acute coronary
      syndromes.

PMID- 15727721
TI  - Reversal of atherosclerosis with aggressive lipid lowering.

PMID- 15727723
TI  - Treatment of the metabolic syndrome: the impact of lifestyle modification.
AB  - Along with the increasing prevalence of obesity comes a constellation of
      metabolic derangements: dyslipidemias, hypertension, insulin resistance, and
      glucose intolerance, as well as increased prothrombotic and inflammatory markers.
      The association of these factors has been termed the "metabolic syndrome" and
      increases the risk of developing cardiovascular disease. Aside from
      pharmaceutical therapy, lifestyle modification is necessary to aggressively treat
      this syndrome in its entirety. This involves a holistic approach of behavioral
      counseling, education, increased physical activity, and dietary modification.
      Even modest weight loss (7% to 10% of body weight) results in decreased fat mass,
      blood pressure, glucose, low-density lipoprotein, and triglyceride levels. These
      benefits can also translate into improved long-term outcome, especially if weight
      loss and lifestyle alterations are maintained. However, the remaining challenge
      is how to promote long-term adherence to a healthier, more active lifestyle and
      avoid reversion to old habits.

PMID- 15727722
TI  - Raising high-density lipoprotein cholesterol: innovative strategies against an
      old adversary.
AB  - The lipid hypothesis, which was proposed over 100 years ago, is based on the
      premise that dyslipidemia is central to the process of atherosclerosis. Low
      density lipoprotein and lipoprotein(a) are clearly atherogenic, whereas the role
      of very low-density lipoprotein as an independent factor is controversial. The
      only lipoprotein that is clearly antiatherogenic is high-density lipoprotein
      (HDL), which is thought to reduce coronary risk by mediating cholesterol efflux
      from the periphery by way of transportation to the liver for excretion.
      Traditionally, fibric acid derivatives and nicotinic acid were the major
      pharmacologic agents used to raise circulating levels of HDL. Recent therapeutic
      advances have been made in the ability to increase HDL. Apolipoprotein A-I Milano
      and cholesterol ester transfer protein represent novel approaches to the
      pharmacologic therapy of individuals with low HDL levels. The mechanisms and
      clinical implications of these interventions are discussed here.

PMID- 15727724
TI  - The lectin-like oxidized low-density lipoprotein receptor and its role in
      atherosclerosis.
AB  - The lectin-like oxidized low-density lipoprotein receptor (LOX-1), a recently
      identified receptor that plays a role in the uptake of oxidized low-density
      lipoproteins into endothelial cells, has a pivotal role in the pathogenesis of
      atherosclerosis. The ways this receptor takes part in atherosclerosis is through
      uptake of oxidized low-density lipoproteins into endothelial cells, smooth muscle
      cells, and macrophages; decreasing nitric oxide production; increasing
      inflammatory cell recruitment; and increasing smooth muscle cell proliferation.
      LOX-1 is inducible and regulated by multiple factors known to underlie
      atherogenesis. Further understanding of this receptor may lead to potential
      molecular targets for prevention and treatment of atherosclerosis.

PMID- 15727725
TI  - Magnetic resonance imaging in the assessment of coronary artery disease.
AB  - Magnetic resonance imaging (MRI) is gaining importance in cardiology as the
      noninvasive test of choice for patients with a multitude of cardiovascular
      problems. Recently, cardiovascular MRI has emerged as an important noninvasive
      diagnostic modality in the assessment of coronary artery disease. Because of its
      superior spatial resolution, integration of qualitative and quantitative
      methodology, and excellent reproducibility, MRI has advantages over conventional
      noninvasive modalities currently used in the evaluation of coronary artery
      disease. This article reviews the rapidly expanding recent literature that has
      now established cardiovascular MRI as an ideal choice in the evaluation of
      myocardial ischemia (including dobutamine cine MRI and vasodilator perfusion MRI
      techniques). We further discuss the role of delayed contrast-enhanced MRI and low
      dose dobutamine cine MRI for evaluation of myocardial viability. Comparisons with
      more established techniques, such as dobutamine stress echocardiography, single
      photon emission computed tomography perfusion imaging, and positron emission
      tomography, are reviewed.

PMID- 15727726
TI  - Thiazolidinediones and cardiovascular disease.
AB  - Thiazolidinediones hold promise for reducing cardiovascular events and human
      atherosclerosis. Similar to statins and angiotensin-converting enzyme inhibitors,
      peroxisome proliferator activated receptor gamma (PPARgamma) exerts anti
      inflammatory and antiatherosclerotic actions in the vessel wall. A number of
      clinical trials in subjects with or without diabetes have shown that
      thiazolidinedione therapy can reduce in-stent restenosis and delay progression of
      atherosclerosis measured by carotid artery ultrasound. PPARgamma directly
      promotes expression of ATP-binding cassette transporter G1, mediating cellular
      cholesterol efflux to high-density lipoproteins from macrophages, which may
      further explain the potential cardiovascular benefit of this class. Whether the
      benefits observed in animal models will translate in clinical practice is being
      evaluated in several large, randomized controlled trials.

PMID- 15727728
TI  - The use of myeloperoxidase as a risk marker for atherosclerosis.
AB  - The mechanisms of atheroma formation and their ensuing complications and methods
      by which these can be detected have been the focus of several in vitro, in vivo,
      and clinical studies. Myeloperoxidase (MPO) is a microbicidal hemoprotein that
      serves as a part of the neutrophils' armory in host defense. However, the
      oxidation products generated by MPO have now been shown to be related to various
      stages of atheroma development. MPO and its oxidant products have been shown to
      be capable of modifying low-density lipoprotein cholesterol and to be enriched in
      human atheromas and rupture-prone plaques. Clinical studies have suggested an
      association between levels of MPO and the presence of coronary artery disease and
      endothelial dysfunction, and have shown a possible additional role to troponin in
      patients with chest pain.

PMID- 15727727
TI  - Vulnerable plaque: definition, detection, treatment, and future implications.
AB  - Atherosclerosis continues to account for significant morbidity and mortality in
      most of the world. The major proportion of atherosclerosis mortality is related
      to atherosclerotic coronary artery disease, yet there still is not an optimal
      method for making the diagnosis of vulnerable plaque in vivo. The search for such
      an undefined method, along with studies on amelioration of currently available
      technology, gains special significance when the association between the
      qualitative definition of lesions in an individual and cardiovascular risks are
      considered. We, therefore, start by defining the critical lesion of coronary
      atherosclerosis and review the advantages and potential for clinical use of
      various methods to detect the vulnerable plaque and comment on possible future
      implications in this field.

PMID- 15727729
TI  - Hypertension and atherosclerosis: clinical implications from the ALLHAT Trial.
AB  - By failing to recognize the heterogeneity of hypertension, the authors of the
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) study used a faulty premise to conduct a poorly designed clinical trial.
      By failing to control blood pressures equally across study drug groups, ALLHAT
      cannot be considered to be a definitive comparative trial. Being neither a
      monotherapy trial nor a trial that initiated therapy for blood pressure control,
      ALLHAT provided no data to recommend first-line therapy for hypertension, making
      the conclusions invalid. Thiazide-type diuretics increase angiotensin II and
      consequently promote atherosclerosis and arteriolarsclerosis. Angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers retard
      atherosclerosis and are nephroprotective. Multiple randomized controlled trials
      show beneficial clinical outcomes, including cardioprotection and
      nephroprotection, with the use of angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers. These agents, and not thiazide-type diuretics,
      should be used as first-line agents to retard the process of atherosclerosis and
      its clinical outcomes in the setting of arterial hypertension.

PMID- 15727731
TI  - Novel serologic markers of cardiovascular risk.
AB  - New serologic markers of cardiovascular risk continue to be amassed. Among the
      new markers, C-reactive protein, fibrinogen, and homocysteine have enjoyed the
      most acceptance, but newer concepts such as inflammatory cytokines, aspirin
      resistance, and antioxidant deficiency continue to emerge. Traditional cardiac
      risk factors are able to predict less than half of cardiovascular events, and the
      new array of markers have added little to clinical practice, with their use and
      significance remaining unclear. This article analyzes the new serologic markers
      of risk in light of the mechanistic, epidemiologic, and clinical data collected
      over the past decade, and in so doing provides a comprehensive understanding of
      their role.

PMID- 15727730
TI  - Remnant lipoproteins and atherosclerosis.
AB  - A recently developed assay for quantification of remnant-like particle
      cholesterol has provided considerable evidence that reinforces the concept that
      elevated levels of plasma remnants are associated with increased cardiovascular
      disease in different populations and distinct patient groups. In this review, we
      provide a brief summary of the most recently published studies, emphasizing the
      clinical relevance of remnant analysis. We discuss recent evidence that sheds
      light on the mechanisms that may underlie the atherogenicity of remnant
      lipoproteins. Taken together, these data provide new insight into the
      significance of remnant lipoproteins in the onset and development of premature
      atherosclerosis.

PMID- 15727732
TI  - Silent myocardial ischemia: recent developments.
AB  - Silent myocardial ischemia is now in its fourth decade of recognition as a
      clinical syndrome within the spectrum of coronary artery disease. Prior decades
      have seen important research into the pathophysiology, detection, prevalence,
      prognosis, and therapy of this syndrome. More recent developments have continued
      to add data to each of these areas, with particular emphasis on the comparative
      value of various diagnostic procedures and the effect of therapy on prognosis.
      While controversy still exists concerning proper screening guidelines for the
      asymptomatic population, there is a growing consensus that some form of stress
      testing in high-risk individuals (ie, those with multiple coronary risk factors)
      is appropriate.

PMID- 15727734
TI  - Sexual Risk Reduction for Patients with Mental Illness: Evidence of Efficacy and
      Reasons for Hope.

PMID- 15727733
TI  - Vasa vasorum imaging: a new window to the clinical detection of vulnerable
      atherosclerotic plaques.
AB  - Complications of vulnerable atherosclerotic plaques (rupture, luminal and mural
      thrombosis, intraplaque hemorrhage, rapid progression to stenosis, spasm, and so
      forth) lead to heart attacks and strokes. It remains difficult to identify what
      plaques are vulnerable to these complications. Despite recent developments such
      as thermography, spectroscopy, and magnetic resonance imaging, none of them is
      approved for clinical use. Intravascular ultrasound (IVUS), a relatively old yet
      widely available clinical tool for guiding intracoronary procedures, is
      increasingly used for characterization of atherosclerotic plaques. However,
      inability of IVUS in measuring plaque activity limits its value in detection of
      vulnerable plaques. In this review, we present new information suggesting that
      microbubble contrast-enhanced IVUS can measure activity and inflammation within
      atherosclerotic plaques by imaging vasa vasorum density. An increasing body of
      evidence indicates that vasa vasorum density may be a strong marker for plaque
      vulnerability. We suggest that a combination of structural assessment (cap
      thickness, lipid core, calcification, etc) and vasa vasorum density imaging by
      IVUS can serve as the most powerful clinically available tool for
      characterization of vulnerable plaques. Due to space limitations, all IVUS images
      and movies are posted on the website of the Ultimate IVUS Collaborative Project:
      http://www.ultimateivus.com.

PMID- 15727736
TI  - Antiretroviral-associated Hepatotoxicity.
AB  - The use of highly active antiretroviral therapy has dramatically reduced HIV
      associated morbidity and mortality. As a result, patients are often being treated
      longer and with more complex medical regimens than ever before, increasing the
      risk for drug interactions and toxicities. In particular, hepatotoxicity caused
      by antiretroviral use has become an increasingly appreciated potential
      complication of drug treatment. All classes of antiretrovirals have been reported
      to induce liver enzyme abnormalities. However, certain antiretrovirals appear
      much more likely to be associated with drug-induced hepatotoxicity. The risk of
      antiretroviral-related hepatotoxicity may be associated with patient-specific
      risk factors, including pre-existing viral hepatitis, baseline elevated liver
      function test results, female gender, and substance abuse. In addition, complex
      drug-drug interactions may potentate the risk of antiretroviral-associated
      hepatotoxicity. Coinfection with hepatitis B or hepatitis C appears to increase
      the risk of antiretroviral-related hepatotoxicity.

PMID- 15727737
TI  - Contemporary Management of Biliary Tract Infections.
AB  - Biliary tract infections are a worldwide problem, with a large financial burden
      on health care. Biliary infections can result from multiple causes, but the most
      common culprit is cholelithiasis. In the past decade, our knowledge of the
      mechanism of disease, microbiology of infections, and management options has
      grown enormously. Although at times perplexing, it is important to understand
      this information to allow for efficient, quality, and cost-effective health care.

PMID- 15727735
TI  - Management of Hepatitis C in HIV-infected Patients.
AB  - As the survival of HIV-infected patients has been lengthening over the past 10
      years as a consequence of effective antiretroviral therapy, hepatitis C virus
      (HCV) coinfection has emerged as a major cause of morbidity and mortality in this
      population. HCV/HIV coinfection is associated with accelerated progression of
      liver disease, untoward effects on the immunologic and virologic response to
      antiretroviral medications, and possibly with a more aggressive course of HIV
      disease. The results of major trials of combination therapy for HCV in coinfected
      patients have clearly established the combination of pegylated interferon-alpha
      with ribavirin as the treatment of choice in this population. However, the
      effectiveness and tolerability of this regimen remains suboptimal, particularly
      in patients with genotype 1 HCV infection. This paper reviews the impact of HCV
      coinfection in HIV-infected patients, outlines current concepts on management and
      antiviral treatment, and discusses some of the newer agents, currently in the
      therapeutic pipeline, that are directed against novel molecular targets.

PMID- 15727739
TI  - Searching for How Best to Accomplish Recommended Rescreening for Genital
      Chlamydia Infection.

PMID- 15727738
TI  - Update on Therapeutic Options for Helicobacter pylori-related Diseases.
AB  - Triple therapy including clarithromycin, amoxicillin, and a proton pump inhibitor
      (PPI) has been recommended as the treatment of choice for Helicobacter pylori
      eradication. This regimen is now challenged by an increasing level of
      clarithromycin resistance that jeopardizes the treatment success. When
      clarithromycin resistance has been detected, or when its rate is known to be high
      in the geographic area, this drug cannot be used. It can be replaced by
      metronidazole, the resistance of which has a limited clinical relevance. Another
      option is to prescribe tetracycline and metronidazole with a PPI or ranitidine
      bismuth citrate. New antibiotics such as levofloxacin or rifabutin can also be
      used in combination with amoxicillin and a PPI. Probiotics can be added to all of
      these regimens to improve compliance by decreasing adverse events. But some
      authors advocate a quadruple therapy as a first-line treatment. Solutions to
      improve the limitations of this last regimen are now being proposed.
      Clarification of the controversial treatment indications such as gastroesophageal
      reflux disease or prevention of nonsteroidal anti-inflammatory drug
      gastroduodenal symptoms has been made. The question of prevention of gastric
      carcinoma by H. pylori eradication remains unanswered.

PMID- 15727740
TI  - A Virus-based Vaccine May Prevent Cervical Cancer.
AB  - High-risk human papillomaviruses (HPVs) are now recognized as the etiologic
      agents of invasive cervical cancer, a major cancer in women. A single HPV type
      (type 16) is responsible for about 50% of the cancers. The major capsid protein
      of papillomaviruses, L1, when expressed by recombinant DNA technology, has the
      intrinsic ability to assemble into virus-like particles (VLPs). In a recent
      study, a vaccine based on HPV 16 VLPs was tested in a placebo-controlled proof-of
      principle trial in young women in the United States. The vaccine was found to
      prevent 100% of incident persistent HPV 16 infections and HPV 16-associated
      cervical intraepithelial neoplasia. These results offer promise that cervical
      cancer will be preventable by an HPV-based vaccine. Studies planned or in
      progress are examining the efficacy of the vaccine in men, in HIV-infected
      individuals, and in other parts of the world. Attempts are being made to prepare
      vaccines that can be administered more easily to large populations.

PMID- 15727741
TI  - Sexually Transmitted Diseases in Travelers.
AB  - International travelers engaging in casual sex are at risk for acquiring sexually
      transmitted diseases (STDs), including HIV. The frequency of international travel
      emphasizes the need for a travel sexual activity history to be included in the
      clinical assessment of any returned traveler. When formulating a differential
      diagnosis, the STD prevalence rates at the travel destination and the risk
      profile of the traveler and the sexual partner need to be considered. Casual sex
      with host country nationals residing in tropical and subtropical areas of the
      developing world increases the traveler's risk for acquiring STDs rarely seen in
      industrialized countries, particularly bacterial genital ulcer diseases.
      Pretravel counseling needs to include education on STD prevention. A post-travel
      STD diagnostic evaluation is indicated when casual sexual activity has occurred
      during travel, regardless of whether symptoms are present.

PMID- 15727745
TI  - [Mental health on the threshold of the XXIst century. Primary care in the
      forefront. Are we up to the challenge?].

PMID- 15727742
TI  - Changes in HIV and AIDS in the United States: Entering the Third Decade.
AB  - The epidemiology of the HIV transmission in the United States has changed
      considerably since the epidemic began. Our increased understanding of the virus
      has fostered development of new treatments to prolong life, and vaccine research
      has increased hope for those at risk in both developed and less developed
      countries. In this review, we provide information about current trends in HIV and
      AIDS among those in the United States most affected by the epidemic.

PMID- 15727744
TI  - The Evolving Role of HIV Counseling and Testing in Resource-limited Settings: HIV
      Prevention and Linkage to Expanding HIV Care Access.
AB  - The role of voluntary counseling and testing (VCT) of HIV in resource-limited
      settings has recently broadened from primarily that of a prevention intervention
      to its identification as the key entry point into expanding access to life-saving
      antiretroviral therapy, additional HIV--specific medical care, and other support
      services. To fulfill this expanded mandate, calls for routine counseling and
      testing in diverse health care settings, in addition to other innovative
      approaches to traditional VCT, are emerging. The efficacy and cost effectiveness
      of traditional facility-based VCT with respect to risk-behavior reduction of HIV
      have been demonstrated rigorously in resource-limited settings. Additional
      research is needed urgently to evaluate the feasibility, acceptability, and
      effectiveness of streamlined counseling and testing interventions that seek to
      reach as many individuals as possible to meet dual prevention and treatment
      goals.

PMID- 15727743
TI  - Primary HIV-1 Infection: Diagnosis, Pathogenesis, and Treatment.
AB  - Primary HIV-1 infection represents the time when the virus is first disseminating
      throughout the body and induces host immune responses. Diagnosing this stage of
      disease requires an understanding of who is at risk, the clinical manifestations
      of primary infection, and how the diagnosis is made. Identifying these
      individuals allows for counseling to prevent further transmission to others and
      the potential benefits associated with early antiretroviral therapy. Moreover,
      studying these individuals provides important insight into the biology of HIV-1
      transmission and immunopathogenesis.

PMID- 15727746
TI  - [The new reference prices: an opportunity for efficient management of
      medication].

PMID- 15727747
TI  - [Five-year follow-up of urinary incontinence in older people in a Spanish rural
      population].
AB  - OBJECTIVE: To determine prevalence, incidence and remission rates and change
      patterns of urinary incontinence (UI) over a 5-year time span. DESIGN:
      Longitudinal study. LOCATION: Basic Health Zone of Cabra (Cordoba). PATIENTS: A
      random age-stratified sample of 827 subjects selected from a total of 5139
      persons > or = 65 years of age and followed up between 1996 and 2001.
      INTERVENTIONS: Home interview. MEASUREMENTS: Questions about detection and level
      of severity of UI, sociodemographic data, and level of functioning. Two logistic
      regression models were created to identify risk factors for the probability to be
      alive and to develop UI, respectively. RESULTS: UI prevalence reached 36% at
      baseline and 46% five years later. Mortality rates were similar in continent and
      incontinent subjects. 54.5% of continent subjects in 1996 remained so in 2001.
      Five-year incidence and remission rates were 29% and 15%, respectively. In both
      sexes, slight and moderate incontinence mainly progressed to moderate and severe
      degrees, whereas severe UI remained unchanged in 40.1%. The main risk factors for
      increased survival and for UI incidence were self-rated health and level of
      functioning. CONCLUSIONS: Prevalence of UI is high, incidence is moderate and
      remission is low. Urinary incontinence is a dynamic problem and does not affect
      mortality. Impaired mobility has a strong influence on UI incidence.

PMID- 15727748
TI  - [Urinary incontinence: another silent epidemic?].

PMID- 15727749
TI  - [Prevalence of tobacco dependency and its prevention in patients with persistent
      asthma].
AB  - OBJECTIVES: To analyse in patients with persistent bronchial asthma the
      prevalence of tobacco dependency and its degree; and to assess measures of
      prevention. DESIGN: Cross-sectional, descriptive study. SETTING: Allergy Service
      of the Lozano Blesa University Hospital, Zaragoza, Spain. PARTICIPANTS: A total
      of 121 patients, from systematic selection of asthmatics attending for
      consultation. MAIN MEASUREMENTS: Questionnaire filled out in the consulting room,
      recording social, demographic and clinical variables. RESULTS: A sample of 121
      patients was obtained, 62.7% women and 37.3% men. They had 5.87 +/- 4.99 years
      mean evolution of asthma. 21.5% were daily smokers, 4.1% occasional smokers,
      27.3% ex-smokers, and 47.1% non-smokers. The ages of starting to smoke were < 10
      years old, 1.7%; 10-15, 30%; 15-20, 56.7%; 20-25, 6.7%, and > 25, 5% (P > .05).
      There were significant differences between gender and tobacco dependency and
      between age and tobacco dependency (P < .01 and P < .014, respectively). 96.8% of
      smokers thought that tobacco was harmful to their health. This figure was 100% in
      daily smokers and 80% in occasional smokers (P < .02). 83.9% of smokers had the
      intention of giving up. Counselling to give up was received from the specialist
      (41.9%), the primary care doctor (12.9%), and both (9.7% of cases). 35.5%
      received no counselling. CONCLUSIONS: The prevalence of tobacco dependency in
      patients with persistent asthma is lower than in the population as a whole; over
      a third receive no counselling about giving up. Interventions must be conducted
      in still healthy smokers and chronically ill patients in both primary and
      specialist care.

PMID- 15727750
TI  - [Characteristics of health care demand in family medicine clinics in a health
      area of the community of Valencia].
AB  - OBJECTIVE: To measure with primary data the kinds of family doctor consultations,
      the reasons for them and the interruptions. DESIGN: Observational, transversal,
      and multi-centred study. SETTING: All the health centres in Area 17 of the
      Community of Valencia. PARTICIPANTS: Representative sample of 2051 patients
      belonging to 20 family medicine lists at the 13 health centres in the Area,
      selected by sampling stratified for health centres and randomised by medical key.
      MAIN MEASUREMENTS: All the activity occurring during the working day was
      monitored by an outside observer in the consulting room, who recorded the types
      of consultation (prior appointment, on-demand, scheduled, urgent, at home, by
      phone or through a family member) and the reasons for them (as a function of
      their clinical content for acute pathology, chronic pathology or preventive
      activities, bureaucratic-administrative reasons or to collect test results). The
      interruptions to the consultation were recorded. The means, percentages and 95%
      confidence limits were calculated. RESULTS: Women occasioned 57.5% (95% CI, 55.4
      59.6) of demand; and the elderly, 35.9% (33.6%-38.2%). Mean attendance time was
      5.38 +/- 4.45 minutes. 23.6% (25.4%-21.8%) attended without prior appointment; in
      14.7% (16.2%-13.2%) a family member attended; 6.6% (7.7%-5.5%) were urgent; and
      0.7% (1.1%-0.3%) were telephone consultations. 65.3% (67.4%-63.2%) of
      consultations were bureaucratic, and preventive measures were taken only in 3.4%
      (4.2%-2.6%). 21.8% (23.6%-20%) of patients consulted for clinical + bureaucratic
      reasons; and 35.5% (37.6%-33.4%), solely for bureaucratic reasons. In 12% (13.4%
      10.6%) there were interruptions, mainly for phone calls (3.9%). CONCLUSION: The
      over-65s caused over a third of all consultations. There was a high attendance
      without a prior appointment. There were few preventive activities. In
      consultations, bureaucratic activity takes up more time than clinical activity
      (care and prevention).

PMID- 15727751
TI  - [Validation of the SCOFF questionnaire for screening the eating behaviour
      disorders of adolescents in school].
AB  - OBJECTIVE: To determine the internal consistency and criteria validity of the
      SCOFF questionnaire for screening adolescent eating behaviour disorders. DESIGN:
      Validation study with stochastic sampling. SETTING: Three schools at Bucaramanga,
      Colombia. PARTICIPANTS: 241 students selected at random from 1595 possible ones.
      MAIN INTERVENTIONS: SCOFF questionnaire and semi-structured CIDI interview,
      administered independently. MAIN MEASUREMENTS: Social and personal details,
      Cronbach's alpha, sensitivity analysis, specificity, forecast values, Cohen mean
      kappa test, and ROC curve. RESULTS: Sensitivity found was 81.9% (95% CI, 70.7
      89.7) and specificity, 78.7% (95% CI, 71.7-84.6). The area under the ROC curve
      was 0.8596 (95% CI, 0.8108-0.9084); the Cronbach's alpha test, 0.436, and the
      Cohen mean kappa, 0.554 (95% CI, 0.425-0.683). CONCLUSIONS: The SCOFF
      questionnaire is an acceptable alternative for screening groups of adolescents
      because of its simplicity and speed of administration.

PMID- 15727752
TI  - [Adventures and misadventures of solitary sailors on the sea of uncertainty].

PMID- 15727754
TI  - [Can digital cameras in a primary care centre be a good teaching tool?].

PMID- 15727753
TI  - [The RECORD project. continuous blood glucose monitoring among high risk subjects
      for developing diabetes in Spanish primary health care].
AB  - OBJECTIVE: To evaluate the accuracy of continuous blood glucose monitoring (CBGM)
      in order to asses diagnostic procedures and predict glycaemic status in type 2
      prediabetes. DESIGN: Observational, multicenter, cross-sectional (phase 1) plus
      longitudinal, cohort follow-up study (phase 2). SETTING: Five primary health-care
      centers. INTERVENTIONS: A total of 84 high-risk subjects will be included after a
      non-diabetic oral glucose tolerance test (OGTT). A first CBGM using a
      subcutaneous microdialysis glucose sensor technique in order to obtain a
      continuous profile will be carried out. Two different cohorts, subjects with
      normal OGTT (n = 42) and individuals with prediabetic hyperglycemia (n = 42) will
      be established. Diagnoses will be revised at 12 and 24 month follow-up by means
      of an OGTT together with a new monitoring. MAIN MEASUREMENT: Demographical,
      clinical (including metabolic syndrome items), basic, and advanced analyses
      (inflammation emergent markers, insulinemia, C-peptide). CBGM computerized
      analysis comparing fasting, preprandial, postprandial, nocturnal period, and area
      under the curve of continuous profile with regular diagnoses, taking into account
      temporary concordance. Relationship of CBGM parameters with normal glucose
      tolerance or diabetes incidence. Evaluation of day-to-day quality of life of CBGM
      users by means of an standardized Likert questionnaire. DISCUSSION: This study
      seeks to demonstrate the effectiveness and feasibility of CBGM, more
      physiological than OGTT and based on an underestimated random blood glucose
      diagnostic criterion. This innovative system may provide interesting scientific
      data in the field of type 2 prediabetes.

PMID- 15727755
TI  - [Burn-out in Spanish general practitioners].

PMID- 15727756
TI  - [Hepatic adenoma related to oral contraceptives use].

PMID- 15727757
TI  - [Gastro-intestinal toxicity of rofecoxib].

PMID- 15727758
TI  - [Analysis of interventions with family members caring for people with dementia: a
      question of method and not of efficacy?].

PMID- 15727759
TI  - [Buscapine for sialorrhoea too].

PMID- 15727761
TI  - Killing a panda.

PMID- 15727762
TI  - Management of portal hypertension.

PMID- 15727760
TI  - [Reconciling public medicine and the private pharmaceutical industry].

PMID- 15727763
TI  - Ogilvie?: I remember that name.

PMID- 15727764
TI  - Advances in parathyroidectomy.

PMID- 15727765
TI  - Anticoagulation: The rest of the story.

PMID- 15727766
TI  - Wound healing: Why hasn't it healed?

PMID- 15727767
TI  - Pediatric musculoskeletal tumors.

PMID- 15727769
TI  - Advanced internet search tips; useful utilities and attractive add-ins.

PMID- 15727768
TI  - Alternative flaps as secondary approaches to breast reconstruction: Part 4 of the
      6-part series on current concepts in breast reconstruction.

PMID- 15727770
TI  - Hepatic abscess: Current concepts in diagnosis and treatment.

PMID- 15727771
TI  - Teaching medical humanities in the tradition of John Dewey.

PMID- 15727772
TI  - A shift of paradigms in defining merit.

PMID- 15727774
TI  - Fighting inequalities in quality health care.

PMID- 15727773
TI  - Does the latex glove fit the invisible hand? Application of market ideology to
      the doctor/patient relationship.

PMID- 15727775
TI  - John's game.

PMID- 15727776
TI  - Mandatory reporting of domestic violence: why it would be a mistake.

PMID- 15727777
TI  - Physicians and cloning?

PMID- 15727778
TI  - The use of incarceration and forced detention as a method of fetal protection for
      substance-abusing pregnant women.

PMID- 15727779
TI  - Withholding or withdrawing life support: When patients and physicians collide.

PMID- 15727780
TI  - Aortic injury in a young go-cart enthusiast.

PMID- 15727782
TI  - Do managed care organizations determine the future of medical technology?

PMID- 15727781
TI  - Growing up.

PMID- 15727783
TI  - Residency reform.

PMID- 15727784
TI  - Biliary drainage update.

PMID- 15727785
TI  - Closing the belly: What is the best way?

PMID- 15727786
TI  - Review of laparoscopic incisional and ventral hernia repairs.

PMID- 15727787
TI  - Anaplastic thyroid carcinoma: An update.

PMID- 15727789
TI  - Minimally invasive parathyroidectomy and parathyroid imaging.

PMID- 15727788
TI  - Laparoscopic adrenalectomy for pheochromocytoma--a new standard?

PMID- 15727790
TI  - Dendritic cells: what do they do?

PMID- 15727791
TI  - Donor bone marrow: improving allograft tolerance with donor bone marrow
      protection.

PMID- 15727792
TI  - Orthotopic liver transplant and hepatic resection: Lessons learned from
      complimentary disciplines.

PMID- 15727793
TI  - Getting the most from your PDA: What else can you do with it?

PMID- 15727794
TI  - Ensuring excellence and competence in surgery: the imperative of mentorship from
      historical and philosophical perspectives.
AB  - PURPOSE: How can the surgical disciplines (1) attract and recruit students of the
      highest capabilities and ideals; (2) ensure professional competency; and (3)
      maximize efficacy and safety of biotechnology translated to patient care?
      METHODS: Critique of the occidental humanistic literature. RESULTS: The
      imperative of mentorship is grounded in the philosophical traditions of
      occidental society dating from antiquity. CONCLUSION: This essay affirms that
      imperative in relationship to the surgical disciplines from an historical
      perspective.

PMID- 15727795
TI  - Back pain and fever.

PMID- 15727796
TI  - Angiosarcoma of the breast: A case report and literature review.
AB  - PURPOSE: Primary angiosarcoma of the breast is a rare occurrence. METHODS: We
      report a case of a 35- year-old woman who presented with a highly vascular mass
      that had nearly replaced her right breast. RESULTS: Initial diagnosis reported
      the tumor as benign. However, permanent sections were sent to the Mayo Clinic,
      where the diagnosis of angiosarcoma of the breast was confirmed. The mass was
      removed via a total mastectomy. Adjuvant chemotherapy was also prescribed. A
      review of the literature suggested that the benefits of adjuvant chemotherapy
      were not well defined, but in the case described, adjuvant chemotherapy appeared
      to offer the best prognosis. CONCLUSIONS: Preoperative radiography is generally
      not indicated for angiosarcoma. Primary angiosarcoma of the breast is difficult
      to diagnose, with no pathognomonic features radiographically. We concluded that
      solid-appearing breast tumors, which are also highly vascular, should be
      considered malignant until proven otherwise. Surgical removal followed by
      adjuvant chemotherapy appears to afford the best prognosis.

PMID- 15727797
TI  - Small-cell undifferentiated carcinoma of neuroendocrine type originating in the
      gallbladder.
AB  - PURPOSE: We report a case of small-cell undifferentiated carcinoma with
      neuroendocrine (SCUCN) of the gallbladder in a 67-year-old man who presented with
      suspected cholelithiasis. Treatment included a cholecystectomy and a 4-cycle
      course of etoposide and carboplatin. CONCLUSIONS: Small-cell undifferentiated
      carcinoma with neuroendocrine features of the gallbladder is a rare disease with
      approximately 30 cases reported in the literature. Clinical characteristics
      include an association with cholelithiasis, an elderly age distribution, a female
      preponderance, and a correlation with cigarette smoking. It is known to behave
      aggressively and carry a grave prognosis, with extensive local invasion and early
      metastasis being characteristic. Medical and surgical therapies exist and have
      demonstrated best results when used in combination.

PMID- 15727798
TI  - Limitations.

PMID- 15727800
TI  - Extrapituitary effects of the growth hormone-releasing hormone.
AB  - Growth hormone-releasing hormone (GHRH) is a neuropeptide secreted by the
      hypothalamus that stimulates the synthesis and release of growth hormone (GH) in
      the pituitary. Accumulating evidence suggests that in addition to GHRH's
      neuroendocrine action, GHRH is present in several extrahypothalamic tissues and
      is involved in a variety of cellular processes. Its function is related to the
      regulation of cell proliferation and differentiation of various nonpituitary cell
      types. In certain cases, ectopic production of GHRH has also been implicated in
      carcinogenesis. The mechanisms by which GHRH affects the peripheral
      extrapituitary tissues remain poorly understood, but it is likely that classic
      neuroendocrine action as well as paracrine and autocrine pathways are involved.
      Some headway has been made in the identification of extrapituitary receptors for
      GHRH and cDNA as splice variants of these GHRH receptors found in various tumors.
      The fact that the nonpituitary GHRH receptors are not fully identified, however,
      remains the major obstacle in studying, at a more mechanistic level, the action
      of local GHRH. This review summarizes the information available regarding the
      role of GHRH in the extrapituitary tissues with emphasis on its potential
      therapeutic and diagnostic applications.

PMID- 15727801
TI  - IRS-1 and vascular complications in diabetes mellitus.
AB  - The expected explosive increase in the number of patients with diabetes mellitus
      will increase the stress on health care. Treatment is focused on preventing
      vascular complications associated with the disorder. In order to develop better
      treatment regimens, the field of research has made a great effort in
      understanding this disorder. This chapter summarizes the current views on the
      insulin signaling pathway with emphasis on intracellular signaling events
      associated with insulin resistance, which lead to the prothrombotic condition in
      the vasculature of patience with diabetes mellitus.

PMID- 15727802
TI  - Structural and functional properties of CCN proteins.
AB  - The CCN family currently comprises six members (CCN1-6) that regulate diverse
      cell functions, including mitogenesis, adhesion, apoptosis, extracellular matrix
      (ECM) production, growth arrest, and migration. These properties can result in a
      multiplicity of effects during development, differentiation, wound healing, and
      disease states, such as tumorigenesis and fibrosis. CCN proteins have emerged as
      major regulators of chondrogenesis, angiogenesis, and fibrogenesis. CCN proteins
      are mosaic in nature and consist of up to four structurally conserved modules, at
      least two of which are involved in binding to cell surfaces via molecules that
      include integrins, heparan sulfate proteoglycans, and low-density lipoprotein
      receptor-related protein. CCN proteins use integrins as signal transducing
      receptors to regulate context-dependent responses in individual cell types. The
      involvement of integrins in mediating CCN signaling allows for considerable
      plasticity in response because some effects are specific for certain integrin
      subtypes and integrin signaling is coordinated with other signaling pathways in
      the cell. In addition to their own biological properties, CCN proteins regulate
      the functions of other bioactive molecules (e.g., growth factors) via direct
      binding interactions. CCN molecules demonstrate complex multifaceted modes of
      action and regulation and have emerged as important matricellular regulators of
      cell function.

PMID- 15727803
TI  - Stanniocalcin: no longer just a fish tale.
AB  - Stanniocalcin was originally described as a hormone with calcitonin-like actions
      in fish. During the last decade, mammalian forms of stanniocalcin have been
      identified, and this discovery has led to important advances in our understanding
      of this enigmatic polypeptide hormone. This review briefly covers some early
      studies on stanniocalcin in fish and then provides a more in-depth look at some
      of the more intriguing, new aspects of its functions in mammals. The roles of
      stanniocalcin in renal function, metabolism, angiogenesis, pregnancy and
      lactation, bone formation, and neural protection are discussed, along with new
      information relating to its receptor-mediated sequestration and accumulation in
      target cell organelles.

PMID- 15727804
TI  - Thyroid hormone transporters.
AB  - Thyroid hormone is essential for the development of the brain and the nervous
      system. Cellular entry is required for conversion of thyroid hormones by the
      intracellular deiodinases and for binding of T(3) to its nuclear receptors.
      Several transporters capable of thyroid hormone transport have been identified.
      Functional expression studies using Xenopus laevis oocytes have so far identified
      two categories of transporters involved in thyroid hormone uptake (i.e., organic
      anion transporters and amino acid transporters). Among the organic anion
      transporters, both Na(+) taurocholate cotransporting polypeptide (NTCP) and
      various members of the organic anion transporting polypeptide (OATP) family
      mediate transport of iodothyronines. Because iodothyronines are a particular
      class of amino acids derived from tyrosine residues, it is no surprise that some
      amino acid transporters have been shown to be involved in thyroid hormone
      transport. We have characterized monocarboxylate transporter 8 (MCT8) as a very
      active and specific thyroid hormone transporter, the gene of which is located on
      the X chromosome. MCT8 is highly expressed in liver and brain but is also widely
      distributed in other tissues. MCT8 shows 50% amino acid identity with a system T
      amino acid transporter 1 (TAT1). TAT1, also called MCT10, has been characterized
      to transport aromatic amino acids but no iodothyronines. We have also found that
      mutations in MCT8 are associated with severe X-linked psychomotor retardation and
      strongly elevated serum T(3) levels in young boys.

PMID- 15727805
TI  - Phytoestrogens and colorectal cancer prevention.
AB  - Because colorectal cancer (CRC) is a leading cause of cancer mortality in the
      Western industrialized world, future chemopreventive strategies will be of high
      socioeconomic importance. Lower CRC incidences in Far Eastern countries in part
      may be attributed to high nutritional intake of soy and its abundance in
      phytoestrogens. Phytoestrogens are plant-derived substances which, due to
      molecular similarities to endogenous estrogens, distinctly interact with estrogen
      receptors ERalpha and ERbeta. Both genomic and nongenomic mechanisms have been
      shown to be responsible for possible anticarcinogenic properties of
      phytoestrogens, such as induction of apoptosis and inhibition of tyrosine kinases
      and DNA topoisomerases. This chapter provides a comprehensive review of a variety
      of studies exploring possible relations between phytoestrogen uptake and CRC
      risk. While in vitro and animal studies in general are somewhat supportive of a
      protective role of phytoestrogens against CRC, epidemiological work so far
      performed does not allow any conclusion on this issue. Studies about mechanisms
      of phytoestrogenic action against CRC development have been evaluated as well.
      Because estrogens, vitamin D, and calcium are frequently suggested to be
      important in CRC prevention, studies concentrating on interactions of
      phytoestrogens with these substances have been performed. Although support in
      evidence for a protective effect of phytoestrogens against CRC has increased over
      the last decade, it is still too early to give a definite recommendation,
      especially in view of enduring inconsistencies about concentrations most likely
      to be effective. Further experimental, and particularly epidemiological, studies
      are required to advance our understanding of the role of phytoestrogens against
      colon carcinogenesis.

PMID- 15727806
TI  - Transcriptional activities of retinoic acid receptors.
AB  - Vitamin A derivatives plays a crucial role in embryonic development, as
      demonstrated by the teratogenic effect of either an excess or a deficiency in
      vitamin A. Retinoid effects extend however beyond embryonic development, and
      tissue homeostasis, lipid metabolism, cellular differentiation and proliferation
      are in part controlled through the retinoid signaling pathway. Retinoids are also
      therapeutically effective in the treatment of skin diseases (acne, psoriasis and
      photoaging) and of some cancers. Most of these effects are the consequences of
      retinoic acid receptors activation, which triggers transcriptional events leading
      either to transcriptional activation or repression of retinoid-controlled genes.
      Synthetic molecules are able to mimic part of the biological effects of the
      natural retinoic acid receptors, all-trans retinoic acid. Therefore, retinoic
      acid receptors are considered as highly valuable therapeutic targets and limiting
      unwanted secondary effects due to retinoid treatment requires a molecular
      knowledge of retinoic acid receptors biology. In this review, we will examine
      experimental evidence which provide a molecular basis for the pleiotropic effects
      of retinoids, and emphasize the crucial roles of coregulators of retinoic acid
      receptors, providing a conceptual framework to identify novel therapeutic
      targets.

PMID- 15727807
TI  - Biochemical and Ionic signaling mechanisms for ACTH-stimulated cortisol
      production.
AB  - Adrenocorticotropic hormone (ACTH)-stimulated cortisol production by adrenal zona
      fasciculata cells requires coordinated biochemical and ionic signaling mechanisms
      that employ adenosine 3', 5'-cyclic monophosphate (cAMP) and Ca(2+) as
      intracellular messengers. As the primary messenger generated in response to ACTH
      receptor activation, cAMP acts at multiple sites to produce the full
      steroidogenic response that includes both rapid and delayed components.
      Biochemically, cAMP activates and induces the expression of multiple proteins
      that function in converting cholesterol to cortisol. These include the steroid
      acute regulatory (StAR) protein as well as steroidogenic enzymes. cAMP also
      inhibits a background K(+) channel (bTREK-1), which sets the resting potential of
      adrenal zona fasciculata (AZF) cells, thereby triggering membrane depolarization
      and Ca(2+) entry through voltage-gated Ca(2+) channels. Ca(2+) also accelerates
      the production of cortisol from cholesterol by activating or inducing the
      synthesis of steroidogenic proteins. In this scheme, background K(+) channels act
      pivotally by transducing a hormonal signal at the cell membrane to an ionic
      signal, leading to depolarization-dependent Ca(2+) entry. In this way, ACTH
      receptor activation increases cAMP and Ca(2+) in the AZF cell, yielding the full
      steroidogenic response. In addition to acutely regulating the activity of AZF
      cell ion channels, ACTH and cAMP also regulate the expression of genes coding for
      these ion channels. The tonic control of the expression of AZF cell ion channels
      through the hypothalamic-pituitary-adrenal axis suggests that prolonged
      stimulation of the AZF cell by ACTH may alter the electrical properties of these
      cells in a manner which matches the organism's requirement for cortisol.

PMID- 15727808
TI  - ATP-dependent chromatin remodeling complexes and their role in nuclear receptor
      dependent transcription in vivo.
AB  - Nuclear receptors (NRs) are ligand-dependent transcription factors that mediate
      transcription of target genes in chromatin. Modulation of chromatin structure
      plays an important part in the NR-mediated transcription process. ATP-dependent
      chromatin remodeling complexes have been shown to be intimately involved in NR
      mediated transcription. In this review, we examine the role of chromatin
      remodeling complexes in facilitating the recruitment of coregulators and basal
      transcription factors. In addition, the role of subunit specificity within the
      chromatin remodeling complexes, the complexes' influence on remodeling activity,
      and complexes' recruitment to the NR-responsive promoters are discussed.

PMID- 15727809
TI  - Novel roles for acylation stimulating protein/C3adesArg: a review of recent in
      vitro and in vivo evidence.
AB  - Recent experimental evidence is shedding more light on the physiological actions
      of acylation-stimulating protein (ASP)/C3adesArg. The role of ASP in regulating
      lipid metabolism has primarily focused on its participation in the stimulation of
      triglyceride synthesis (TGS) and glucose transport. Although there is no doubt
      that ASP, an adipocyte-produced hormone, plays a key physiological role,
      accumulating evidence suggests that the effects of ASP go beyond its acute
      effects on lipid metabolism. In this review, we present novel findings of
      ASP/C3adesArg effects on preadipocyte differentiation. In 3T3-L1 and 3T3-F442A
      cells, ASP can substitute for insulin and enhance differentiation as measured by
      intracellular lipid droplet accumulation, clonal expansion, and increased
      expression of differentiation markers. Specifically, ASP increased basal TGS by
      250% after 9 days differentiation, with similar effects induced by insulin. With
      ASP treatment, expression of C/EBPdelta was up-regulated early in differentiation
      (day 2) and decreased thereafter. Expression of PPARgamma and late markers of
      differentiation, such as adipsin and diacylglycerol acyltransferase-1, were also
      increased. Effects on clonal expansion were indicated by a twofold increase in
      [(3)H] thymidine incorporation in 3T3-L1 cells compared to treatment with IBMX +
      DX alone. Further, the effects of ASP extended beyond adipose tissue to endocrine
      effects on hormone secretion of insulin (pancreatic cells); cytokines TNFalpha,
      IL-1beta, and IL-6 (myeloid cells); prolactin, growth hormone, and
      adrenocorticotropin (pituitary cells). Finally, the potential implication of
      C5L2, the newly discovered ASP receptor, and its expression profile in various
      tissues are discussed relative to ASP function.

PMID- 15727810
TI  - STAT3 and transactivation of steroid hormone receptors.

PMID- 15727811
TI  - Coactivators in gene regulation by STAT5.
AB  - Signal transducer and activator of transcription 5 (STAT5) is a member of the
      STAT family of transcription factors that relay the effect of diverse cytokines,
      hormones, and growth factors by regulating the transcription of distinct target
      genes. This function is emphasized by its crucial role in the development of the
      mammary gland and the hematopoietic system. Cytokine receptor-associated Janus
      kinases (JAKs) induce dimerization, nuclear translocation, and DNA binding
      through tyrosine phosphorylation of STAT5. STAT5 regulates the expression of
      cytokine target genes by binding to gamma interferon-activated sequence (GAS)
      motifs. Transcriptional activation requires the contact of STAT5 to coactivators
      and components of the transcription machinery. Another important point in
      transcriptional activation is the cooperation with other transcription factors
      that bind in close vicinity to the target gene promoters and enhancers. Their
      concerted action can result in an enhanced binding to the promoters or in
      cooperative recruitment of coactivators. In addition, cross-talk with other
      signaling pathways as well as secondary modifications of STAT5 have been
      described to affect transactivation function.

PMID- 15727812
TI  - New insights into the regulation of mammalian sex determination and male sex
      differentiation.
AB  - In mammals, sex development is a genetically and hormonally controlled process
      that begins with the establishment of chromosomal or genetic sex (XY or XX) at
      conception. At approximately 6 to 7 weeks of human gestation or embryonic day
      e11.5 in the mouse, expression of the Y chromosome-linked sex determining gene
      called SRY (described in detail in this chapter) then initiates gonadal
      differentiation, which is the formation of either a testis (male) or an ovary
      (female). Male sex differentiation (development of internal and external
      reproductive organs and acquisition of male secondary sex characteristics) is
      then controlled by three principal hormones produced by the testis: Mullerian
      inhibiting substance (MIS) or anti-Mullerian hormone (AMH), testosterone, and
      insulin-like factor 3 (INSL3). In the absence of these critical testicular
      hormones, female sex differentiation ensues. This sequential, three-step process
      of mammalian sex development is also known as the Jost paradigm. With the advent
      of modern biotechnologies over the past decade, such as transgenics, array-based
      gene profiling, and proteomics, the field of mammalian sex determination has
      witnessed a remarkable boost in the understanding of the genetics and complex
      molecular mechanisms that regulate this fundamental biological event.
      Consequently, a number of excellent reviews have been devoted to this topic. The
      purpose of the present chapter is to provide an overview of selected aspects of
      mammalian sex determination and differentiation with an emphasis on studies that
      have marked this field of study.

PMID- 15727813
TI  - The role of alcohol and steroid hormones in human aggression.
AB  - The association between alcohol and aggressive behavior is well established
      although a direct causal relationship has proven hard to demonstrate. There are,
      however, indications that alcohol facilitates aggression in individuals who
      already have a predisposition to behave aggressively. Aggressive personality
      disorders have in turn been explained by elevated testosterone level. A one-to
      one relation between increased levels of testosterone and aggression has been,
      nevertheless, difficult to reveal. Two metabolites of testosterone, estradiol and
      5alpha-dihydrotestosterone (DHT), have been studied much less in human aggressive
      behavior. Estradiol might reduce androgenic effects and have a counterbalancing
      influence on aggression. DHT, again, has a much higher affinity than testosterone
      to androgen receptors, and there are indications that some of the effects of
      testosterone-mediating aggressive behavior occur after aromatization. Disregard
      of seasonal and circadian fluctuations in male testosterone production might be
      responsible for some of the inconclusive testosterone-aggression results. In
      addition, increasing age decreases both aggressive behavior and testosterone
      production in males. Cortisol has yielded conflicting results as a mediator in
      aggressive behavior. Both higher and lower levels have been reported in
      aggressive and abusive men. Finally, the acute and chronic effects of alcohol
      influence the steroid hormone levels in various ways. The present understanding
      of the etiology of aggression is still vague. It is clear that a multidimensional
      approach, combining both biological and psychosocial factors, will be necessary
      for the development of a more general concept of human aggression in the future.

PMID- 15727814
TI  - Sporadic colorectal cancer--role of the commensal microbiota.
AB  - There are vast numbers of bacteria present within the human colon that are
      essential for the host's well being in terms of nutrition and mucosal immunity.
      While certain members of the colonic microbiota have been shown to promote the
      host's health there are also numerous studies that have implicated other members
      of the colonic microbiota in the development of colorectal cancer, a prominent
      malignancy within the western world. In this review we consider the evidence for
      the role of bacteria in colorectal cancer from molecular and animal model
      studies. We focus on some of the mechanisms by which the colonic microbiota
      drives the progression towards colorectal malignancy including generation of
      reactive metabolites and carcinogens, alterations in host carbohydrate expression
      and induction of chronic mucosal inflammation.

PMID- 15727815
TI  - Reverse genetics of negative-stranded RNA viruses: a global perspective.
AB  - The advent of reverse genetics technology has revolutionized the field of RNA
      viruses. It is now possible to manipulate even negative-stranded RNA viruses at
      will, and evaluate the effects of these changes on the biology and pathogenesis
      of these viruses. The fundamental insights gleaned from the reverse genetics
      based studies over the last several years have provided a new momentum for the
      development of designed therapies for the control and prevention of these viral
      pathogens. The recombinant viruses have been exploited also as vectors for
      devising targeted therapies for non-viral diseases such as malignancies, and in
      gene therapy for inherited disorders. This review provides a brief summary of the
      stumbling blocks and the successes in the development of the technology for the
      negative-stranded RNA viruses. The many and varied applications of the
      recombinant vectors are also outlined.

PMID- 15727816
TI  - Effect of over-expression of phasin gene from Aeromonas hydrophila on
      biosynthesis of copolyesters of 3-hydroxybutyrate and 3-hydroxyhexanoate.
AB  - The gene phaPAh, encoding the protein phasin that is associated with poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) granule of Aeromonas hydrophila
      4AK4, was cloned and characterized. Recombinant strains harboring additional
      copies of the phasin gene (phaPAh) and the polyhydroxyalkanoate (PHA) synthase
      gene (phaCAh) accumulated PHBHHx copolyesters consisting of 21 mol% 3
      hydroxyhexanoate (3HHx) as compared to 14 mol% 3HHx produced by wild type strain.
      The molecular weight of PHBHHx produced by the above recombinants was lower than
      that obtained from the wild type strain grown under similar conditions. Over
      expression of phaPAh led to the production of more PHA granules but with reduced
      sizes. SDS-PAGE showed that PhaPAh was the predominant protein present in the
      PHBHHx granules. The RT-PCR results suggested that phasin PhaPAh, regulated
      phaCAh gene at the transcription level. Gene PhaPWe from Wautersia eutropha
      (formerly Ralstonia eutropha; encoding a 20 kDa protein with low amino acid
      homology to the A. hydrophila 13 kDa protein) cloned into A. hydrophila 4AK4
      exhibited similar effects on PHBHHx production and PHBHHx composition. These data
      suggest that the phasins could represent a protein family possessing similar
      functions but different structures.

PMID- 15727817
TI  - Evolutionary origins and sequence of the Escherichia coli O4 O-antigen gene
      cluster.
AB  - Escherichia coli express many types of O antigen, present in the outer membrane
      of the Gram-negative bacterial cell wall. O-Antigen biosynthesis genes are
      clustered together and differences seen in O-antigen types are due to genetic
      variation within this gene cluster. Sequencing of the E. coli O4 O-antigen gene
      cluster revealed a similar gene order and high levels of similarity to that of E.
      coli O26; indicating a common ancestor. These lateral transfer events observed
      within O-antigen gene clusters may occur as part of the evolution of the
      pathogenic clones.

PMID- 15727818
TI  - Streptococcus suis serotype 2 binding to extracellular matrix proteins.
AB  - Streptococcus suis serotype 2 is a major swine and human pathogen that causes
      septicemia and meningitis. The ability of S. suis serotype 2 to bind to different
      extracellular matrix (ECM) proteins was evaluated by ELISA. All 23 strains tested
      bound to plasma and cellular fibronectin and collagen types I, III, and V, some
      to fibrin, vitronectin, and laminin, and none to the other ECM proteins tested.
      An unencapsulated isogenic mutant bound to ECM proteins better than its parental
      encapsulated strain, suggesting that the polysaccharide capsule interfered with
      binding. Cross-inhibition was observed between soluble plasma fibronectin and
      collagens in the ECM adherence assay, indicating that binding domains for both
      proteins exist on the same or nearby bacterial surface molecules. On the other
      hand, pre-incubation with plasma fibronectin increased binding to collagen IV,
      suggesting that S. suis might use fibronectin as a bridging molecule. The results
      of heat treatment and proteolytic digestion suggest that adhesins for these ECM
      proteins are proteinaceous in nature.

PMID- 15727819
TI  - Development of Aspergillus oryzae thiA promoter as a tool for molecular
      biological studies.
AB  - In filamentous fungi, the repertoire of promoters available for exogenous gene
      expression is limited. Here, we report the development and application of the
      thiamine-regulatable thiA promoter (PthiA) in Aspergillus oryzae as a tool for
      molecular biological studies. When PthiA was used to express the enhanced green
      fluorescent protein (EGFP) reporter, the fluorescence in the mycelia was either
      repressed or induced in the presence or absence of thiamine in the culture media,
      respectively. In addition, the expression level from the thiA promoter can be
      controlled by the concentration of external thiamine. Thiamine content in the
      media did not affect mycelial morphology, making the thiA promoter more useful
      compared with alcA and amyB promoters that depend on carbon source for
      regulation. Moreover, as the A. oryzae thiA promoter was also regulated by
      thiamine in A. nidulans, this promoter can be further applied as an inducible
      promoter in other Aspergilli.

PMID- 15727820
TI  - Ceramide glycosylation and fatty acid hydroxylation influence serological
      reactivity in Trypanosoma cruzi glycosphingolipids.
AB  - Ceramide mono (CMH) or dihexoside (CDH) fractions from Trypanosoma cruzi (Dm28c
      clone) were identified as glucosyl and lactosylceramides containing non
      hydroxylated fatty acids. The di-glycosylated form was much more efficiently
      recognized by sera from T. cruzi-immunized rabbits, indicating that glycosylation
      influences antigenicity. Fatty acid hydroxylation was also a determinant of
      serological reactivity, since an alpha-hydroxylated CMH, only present at the Y
      clone, was recognized by the hyperimmune sera. In summary, these data indicate
      that T. cruzi CMHs with non-hydroxylated fatty acids are unable to induce
      antibody responses in animal hosts, which is reverted by the addition of a sugar
      residue or an alpha-hydroxyl group.

PMID- 15727821
TI  - Properties of the thermostable glutamate dehydrogenase of the mesophilic anaerobe
      Peptostreptoccus asaccharolyticus purified by a novel method after over
      expression in an Escherichia coli host.
AB  - Peptostreptococcus asaccharolyticus glutamate dehydrogenase (L-glutamate: NAD+
      oxidoreductase (deaminating); EC 1.4.1.2) overexpressed in Escherichia coli has
      been purified by two new methods. Enzyme made by the first method showed
      remarkable thermophilicity, with a temperature optimum of 60 degrees C, and also
      thermostability, which suggested the second, simpler method, incorporating a heat
      step. This produced 94 mg of homogeneous protein per litre culture medium. The
      basic kinetic parameters for P. asaccharolyticus glutamate dehydrogenase with all
      substrates are revealed at pH 7.0. The enzyme is highly specific for NAD+, with
      values for kcat/Km 405 times greater than for NADP+. In the reverse direction of
      reaction, the kcat/Km value for NADH is almost 1000-fold greater than for NADPH.

PMID- 15727822
TI  - Diversity of thermophilic and non-thermophilic Crenarchaeota at 80 degrees C.
AB  - A hot spring in the solfataric field of Pisciarelli (Naples-Italy) was analysed
      for Archaeal diversity. Total DNA was extracted from the environment, archaeal
      16S rRNA genes were amplified with Archaea specific primers, and a clone library
      consisting of 201 clones was established. The clones were grouped in 10 different
      groups each representing a specific band pattern using restriction fragment
      length polymorphism (RFLP). Members of all 10 groups were sequenced and
      phylogenetically analyzed. Surprisingly, a high abundance of clones belonging to
      non-thermophilic Crenarchaeal clusters were detected together with the
      thermophilic archaeon Acidianus infernus in this thermophilic environment.
      Neither Sulfolobus species nor other hyperthermophilic Crenarchaeota were
      detected in the clone library. The relative abundance of the sequenced clones was
      confirmed by terminal restriction fragment analyses. Amplification of 16S rRNA
      genes from Archaea transferred from the surrounding environment was considered
      negligible because DNA from non-thermophilic Crenarchaeota incubated under
      conditions similar to the solfatara could not be PCR amplified after 5 min.

PMID- 15727823
TI  - The moderately halophilic bacterium Halomonas maura is a free-living diazotroph.
AB  - Halomonas maura is a moderately halophilic bacterium which lives in saline soils
      and synthesises an exopolysaccharide known as mauran. Strain S-31T grew in a
      nitrogen-free medium under an N2 atmosphere; the acetylene reduction assay proved
      positive under specific conditions. We identified the nifH gene in this strain by
      using degenerate oligonucleotides designed from highly preserved gene sequences
      obtained from the alignment of a large number of nifH sequences from different
      microorganisms. Our results lead us to conclude that H. maura is capable of
      fixing nitrogen under microaerobic conditions.

PMID- 15727824
TI  - A Myxococcus xanthus CbpB containing two cAMP-binding domains is involved in
      temperature and osmotic tolerances.
AB  - Our previous data indicated that a Myxococcus xanthus sensor-type adenylyl
      cyclase (CyaA) functions in signal transduction during osmotic stress. However,
      the cAMP-mediated signal transduction pathway in this bacterium was unknown.
      Here, we isolated a clone from a M. xanthus genomic DNA library using
      oligonucleotide probes designed based on the conserved cAMP-binding domains of
      the cAMP-dependent protein kinase (PKA) regulatory subunits. The clone contained
      two open-reading frames (ORFs), cbpA and cbpB, encoding hydrophilic proteins with
      one and two cAMP-binding domains, respectively. The CbpB exhibited partial
      primary structural similarity to PKA regulatory subunits. cbpA and cbpB mutants,
      generated by gene disruption, showed normal growth, development and spore
      germination. However, the cbpB mutant cultured under high- or low-temperature
      conditions exhibited a marked reduction in growth. cbpB mutant cells were also
      more sensitive to osmotic stress than wild-type cells. The cbpA mutant possessed
      normal resistance to such stress. The phenotype of cbpB mutant was similar to
      those of PKA regulatory subunit mutants of some eukaryotic microorganisms.

PMID- 15727825
TI  - Over-expression of xylulokinase in a xylose-metabolising recombinant strain of
      Zymomonas mobilis.
AB  - The broad host range vector pBBR1MCS-2 has been evaluated as an expression vector
      for Zymomonas mobilis. The transformation efficiency of this vector was 2 x 10(3)
      CFU per mug of DNA in a recombinant strain of Z. mobilis ZM4/AcR containing the
      plasmid pZB5. Stable replication for this expression vector was demonstrated for
      50 generations. This vector was used to study xylose metabolism in acetate
      resistant Z. mobilis ZM4/AcR (pZB5) by over-expression of xylulokinase (XK), as
      previous studies had suggested that XK could be the rate-limiting enzyme for such
      strains. Based on the above vector, a recombinant plasmid pJX1 harboring xylB
      (expressing XK) under control of a native Z. mobilis promotor Ppdc was
      constructed. When this plasmid was introduced into ZM4/AcR (pZB5) a 3-fold higher
      XK expression was found compared to the control strain. However, fermentation
      studies with ZM4/AcR (pZB5, pJX1) on xylose medium did not result in any increase
      in rate of growth or xylose metabolism, suggesting that XK expression was not
      rate-limiting for ZM4/AcR (pZB5) and related strains.

PMID- 15727826
TI  - Removal of estrogenic activity of endocrine-disrupting genistein by ligninolytic
      enzymes from white rot fungi.
AB  - Endocrine-disrupting genistein was treated with the white rot fungus
      Phanerochaete sordida YK-624 under ligninolytic condition with low-nitrogen and
      high-carbon culture medium. Genistein decreased by 93% after 4 days of treatment
      and the activities of ligninolytic enzymes, manganese peroxidase (MnP) and
      laccase, were detected during treatment, thus suggesting that the disappearance
      of genistein is related to ligninolytic enzymes produced extracellularly by white
      rot fungi. Therefore, genistein was treated with MnP, laccase, and the laccase
      mediator system with 1-hydroxybenzotriazole (HBT) as a mediator. HPLC analysis
      demonstrated that genistein disappeared almost completely in the reaction mixture
      after 4 h of treatment with either MnP, laccase, or the laccase-HBT system. Using
      the yeast two-hybrid assay system, it was also confirmed that three enzymatic
      treatments completely removed the estrogenic activity of genistein after 4h.
      These results strongly suggest that ligninolytic enzymes are effective in
      removing the estrogenic activity of genistein.

PMID- 15727827
TI  - Detection and quantification of Bifidobacterium lactis LAFTI B94 in human faecal
      samples from a consumption trial.
AB  - A method was developed to allow detection of the probiotic Bifidobacterium lactis
      LAFTI B94 in human clinical samples. A new probe, Laf94p, was developed to
      accomplish colony hybridization of B. lactis B94. PCR detection of B94 was also
      achieved using the species-specific (B. lactis) primer pair. These tests and
      probes allowed detection and quantification of B94 in the human intestinal flora.
      The sensitivity of the probe was assessed by monitoring faecal levels of B94 in
      humans who were fed the culture. In this trial, five volunteers were fed with the
      probiotic. The presence of B94 was assessed daily. Viable B94 could be detected
      at high levels (as high as 1.8 x 10(9) cfu g(-1) wet weight) during the feeding
      period. Four weeks after the feeding stopped, B94 could still be detected in one
      subject. These results indicate that B94 survives in the human gastrointestinal
      tract.

PMID- 15727828
TI  - Fluorescence based assay of GAL system in yeast Saccharomyces cerevisiae.
AB  - The GAL1 promoter is one of the strongest inducible promoters in the yeast
      Saccharomyces cerevisiae. In order to improve recombinant protein production we
      have developed a fluorescence based method for screening and evaluating the
      contribution of various gene deletions to protein expression from the GAL1
      promoter. The level of protein synthesis was determined in 28 selected mutant
      strains simultaneously, by direct measurement of fluorescence in living cells
      using a microplate reader. The highest, 2.4-fold increase in GFP production was
      observed in a gal1 mutant strain. Deletion of GAL80 caused a 1.3-fold increase in
      fluorescence relative to the isogenic strain. GAL3, GAL4 and MTH1 gene deletion
      completely abrogated GFP synthesis. Growth of gal7, gal10 and gal3 also exhibited
      reduced fitness in galactose medium. Other genetic perturbations affected the GFP
      expression level only moderately. The fluorescence based method proved to be
      useful for screening genes involved in GAL1 promoter regulation and provides
      insight into more efficient manipulation of the GAL system.

PMID- 15727829
TI  - Molecular profiling of bacterial species in the rabbit caecum.
AB  - The diversity of bacteria present in the caecum of the rabbit was investigated.
      Partial bacterial 16S rRNA genes from a digested sample collected from the caecum
      of an adult rabbit were amplified by PCR. Sequence analysis of the amplified
      fragments indicated highest similarity was to bacterial sequences previously
      described from other gut environments. However, only one sequence showed
      significant identity (97% threshold) to any previously described bacterial 16S
      rRNA genes. Furthermore, most of the sequences clustered together in groups
      lacking representatives from sequences already described, suggesting that the
      rabbit caecal flora contains organisms not previously described.

PMID- 15727830
TI  - Cholesteryl-6-O-acyl-alpha-D-glucopyranoside of Helicobacter pylori relate to
      relative lysophospholipid content.
AB  - The presence of cholesteryl glucosides and high levels of lysophospholipids are
      elements making the cell wall of Helicobacter pylori unique. In this study, we
      have investigated the relationship between lysophospholipid content and
      cholesteryl glucoside composition of variants of 6 clinical isolates. The samples
      were characterized by diverse outer membrane phospholipase A activity measured as
      lysophospholipid content of the cell wall. A pldA negative mutant was also
      included in the study. Thin-layer chromatography showed that cholesteryl
      glucosides were present in all samples. However, the distribution of cholesteryl
      6-O-acyl-alpha-D-glucopyranoside, cholesteryl-alpha-D-glucopyranoside and
      cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside varied according to
      lysophospholipid content. Cholesteryl-6-O-acyl-alpha-D-glucopyranoside was
      exclusively observed in the isolates/variants with an intact pldA and where a
      significant amount of lysophospholipids could be demonstrated. High
      lysophospholipid content destabilizes membranes. The balance between cholesteryl
      6-O-acyl-alpha-D-glucopyranoside, cholesteryl-alpha-D-glucopyranoside and
      cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside in H. pylori is probably
      important for the stability of the membrane when the lysophospholipid content
      varies.

PMID- 15727831
TI  - Colonial architecture in mixed species assemblages affects AHL mediated gene
      expression.
AB  - Many bacterial species produce metabolites that accumulate in the extracellular
      environment and induce specific transcriptional responses in producing cells.
      This phenomenon, most often referred to as quorum sensing, is thought to
      constitute a self-cell-density sensing mechanism allowing bacterial populations
      to alter gene expression in response to increases in their own density. Quorum
      sensing systems involving N-acyl-L-homoserine lactone (AHL) production and
      response are the most intensively investigated example. In this study we have
      employed a novel technique, known as dielectrophoresis, to investigate the impact
      of colonial architecture on the induction of AHL mediated gene expression. Using
      dielectrophoresis, we constructed artificial mixed species microcolonies with
      specific architectures. In this way, we were able to show that approximately 1000
      Escherichia coli cells layered over an immobilised cluster of approximately 500
      AHL responsive cells alters the response of this cluster to AHLs supplied either
      exogenously or endogenously. These findings lend credence to the hypothesis that
      the accumulation of extracellular metabolites signifies generic crowding in mixed
      species assemblages.

PMID- 15727832
TI  - Bile salt and acid tolerance of Lactobacillus rhamnosus strains isolated from
      Parmigiano Reggiano cheese.
AB  - This study aimed to compare phenotypic and genetic characteristics of
      Lactobacillus rhamnosus strains isolated at the end of the ripening of Parmigiano
      Reggiano cheese and to investigate an important prerequisite of probiotic
      interest, such as the capability to survive at low pH and in presence of bile
      salts. The use of API 50 CH, RAPD-PCR analysis and species-specific PCR allowed
      to ascertain the identity of 63 L. rhamnosus strains. Three L. rhamnosus strains
      isolated from Parmigiano Reggiano cheese, L. rhamnosus ATCC 7469T and the
      commercial strain L. GG were assayed to estimate the resistance to various stress
      factors reproducing in vitro some conditions of the gastro-intestinal environment
      such as low pH and different amounts of bile salts and acids. The behaviour of
      almost all the tested strains isolated from Parmigiano Reggiano cheese resulted
      analogous to that showed by L. GG.

PMID- 15727833
TI  - Detection of putative peptide synthetase genes in Trichoderma species:
      application of this method to the cloning of a gene from T. harzianum CECT 2413.
AB  - Some of the secondary metabolites produced by Trichoderma, such as the peptaibols
      and other antibiotics, have a peptide structure and in their biosynthesis are
      involved proteins belonging to the Non-Ribosomal Peptide Synthetase family. In
      the present work, a PCR-mediated strategy was used to clone a region
      corresponding to an adenylation domain of a peptide synthetase (PS) gene from 10
      different strains of Trichoderma. In addition, and using the fragment isolated by
      PCR from T. harzianum CECT 2413 as a probe, a fragment of 19.0 kb corresponding
      to a PS-encoding gene named salps1, including a 1.5 kb fragment of the promoter,
      was cloned and sequenced. The cloned region of salps1 contains four complete, and
      a fifth incomplete, modules, in which are found the adenylation, thiolation and
      condensation domains, but also an additional epimerization domain at the C
      terminal end of the first module. The analysis of the Salps1 protein sequence,
      taking into consideration published data, suggests that it is neither a peptaibol
      synthetase nor a protein involved in siderophore biosynthesis. The presence of
      two breaks in the open reading frame and the expression of this gene under
      nitrogen starvation conditions suggest that salps1 could be a pseudogene.

PMID- 15727834
TI  - Xylanases and carboxymethylcellulases of the rumen protozoa Polyplastron
      multivesiculatum, Eudiplodinium maggii and Entodinium sp.
AB  - Endoglucanase and xylanase activities of three rumen protozoa, Polyplastron
      multivesiculatum, Eudiplodinium maggii, and Entodinium sp. were compared
      qualitatively by zymograms and quantitatively by measuring specific activities
      against different polysaccharides. A set of carboxymethylcellulases and xylanases
      was produced by the large ciliates whereas no band of activity was observed for
      Entodinium sp. in zymograms. Specific activity of endoglucanases from P.
      multivesiculatum (1.3 micromol mg prot(-1) min(-1)) was twice that of E. maggii,
      whereas xylanase specific activity (4.5 micromol mg prot(-1) min(-1)) was only
      half. Very weak activities were observed for Entodinium sp. A new xylanase gene,
      xyn11D, from P. multivesiculatum was reported and its gene product compared to 33
      other family 11 xylanases. Phylogenetic analysis showed that xylanase sequences
      from rumen protozoa are closely related to those of bacteria.

PMID- 15727835
TI  - Physical organization of phytobeneficial genes nifH and ipdC in the plant growth
      promoting rhizobacterium Azospirillum lipoferum 4VI.
AB  - The physical organization of phytobeneficial genes was investigated in the plant
      growth-promoting rhizobacterium Azospirillum lipoferum 4VI by hybridization
      screening of a bacterial artificial chromosome (BAC) library. Pulsed-field gel
      electrophoresis gave an estimated 5.7-Mb genome size for strain 4VI and a
      coverage level of 9 for the BAC library. The phytobeneficial genes nifH
      (associative nitrogen fixation) and ipdC (synthesis of the phytohormone
      indoleacetic acid) are chromosomal, but no BAC clone containing both genes was
      found, pointing to the absence of any genetic island containing nifH and ipdC. A
      11.8-kb fragment containing nifH was analyzed. Neighboring genes implicated in
      nitrogen fixation (nifH, draT, draG) or not (arsC, yafJ and acpD) were organized
      as in A. brasilense. In contrast, the region located downstream of acpD contained
      four housekeeping genes (i.e. genes encoding DapF-, MiaB- and FtsY-like proteins,
      as well as gene amn) and differed totally from the one found in A. brasilense.

PMID- 15727836
TI  - Fast protocols for the 5S rDNA and ITS-2 based identification of Oenococcus oeni.
AB  - To identify specific marker sequences for the rapid identification of Oenococcus
      oeni, we sequenced the 23S-5S internal transcribed spacer (ITS-2) region and the
      5S rDNA of five different O. oeni strains and three phylogenetically related
      lactic acid bacteria (LAB). Comparative analysis revealed 100% identity among the
      ITS-2 region of the O. oeni strains and remarkable differences in length and
      sequence compared to related LAB. These results enabled us to develop a primer
      set for a rapid PCR-identification of O. oeni within three hours. Moreover, the
      comparison of the 5S rDNA sequences and the highly conserved secondary structure
      provided the template for the design of three fluorescence-labeled specific
      oligonucleotides for fluorescence in situ hybridization (FISH). These probes are
      partial complementary to each other. This feature promotes the accessibility to
      the target sequence within the ribosome and enhances the fluorescence signal. For
      the rapid identification of Oenococci both the 5S rRNA gene and the ITS-2 region
      are useful targets.

PMID- 15727837
TI  - Transcriptional regulation through RfaH contributes to intestinal colonization by
      Escherichia coli.
AB  - The Escherichia coli regulatory protein RfaH contributes to efficient
      colonization of the mouse gut. Extraintestinal pathogenic (ExPEC) as well as non
      pathogenic probiotic E. coli strains rapidly outcompeted their isogenic rfaH
      mutants following oral mixed infections. LPS-core and O-antigen side-chain as
      well as capsular polysaccharide synthesis are among the E. coli virulence factors
      affected by RfaH. In respect of colonization, deep-rough LPS mutants (waaG) but
      not capsular (kps) mutants were shown to behave similarly to rfaH mutants.
      Furthermore, alteration in the length of O-antigen side-chains did not modify
      colonization ability either indicating that it was the regulatory effect of RfaH
      on LPS-core synthesis, which affected intestinal colonization. Loss of RfaH did
      not significantly influence adhesion of bacteria to cultured colon epithelial
      cells. Increased susceptibility of rfaH mutants to bile salts, on the other hand,
      suggested that impaired in vivo survival could be responsible for the reduced
      colonization capacity.

PMID- 15727838
TI  - Pathogenicity of gacA mutant of Pseudomonas aeruginosa PA01 in the silkworm,
      Bombyx mori.
AB  - To investigate the pathogenicity of Pseudomonas aeruginosa in insects, a gacA
      mutant of P. aeruginosa PA01 was constructed by site-directed mutagenesis. The
      mutant was designated as C1. C1 was less virulent to Bombyx mori than the parent
      strain. To complement the gacA gene, P. aeruginosa C1 was transformed with the
      broad host range plasmid pJB3Km1 carrying a 3.9-kbp gacA fragment. The expression
      of the gacA mRNA in C1 (pgacA) was detected. In addition, the complemented mutant
      restored the level and timing of pyocyanin production, indicating that functional
      GacA is produced in the complemented strain. However, no significant difference
      was observed between C1 and C1 (pgacA) with respect to the killing of B. mori
      larvae.

PMID- 15727839
TI  - Effects of exogenous ubiquitin on cell division cycle mutants of
      Schizosaccharomyces pombe.
AB  - Many important cellular processes like cell cycle are regulated by selective
      degradation of short-lived cellular proteins via the ubiquitin-proteasome
      pathway. Deregulation in degradation of any of these controlling molecules can
      lead to abnormalities like malignancies, neurodegenerative disorders, etc.
      Research on effects of exogenously added Ubiquitin (Ub) on cell cycle has been
      lacking. This report describes the effects of exogenously added Ub on the growth
      of Schizosaccharomyces pombe cells. Addition of Ub was found to cause inhibition
      in growth of cells. In temperature sensitive cell division cycle mutant, which
      exhibits arrest at the G2 phase, the exogenously added Ub affected the cell-cycle
      arrest. Addition of Lactacystin, an inhibitor of the proteasome degradation
      pathway, abolished the effects of externally added Ub. A proposal has been made
      on the mechanism through which externally added Ub may exert its effects on
      cells.

PMID- 15727840
TI  - A fungus-type beta-galactofuranan in the cultivated Trebouxia photobiont of the
      lichen Ramalina gracilis.
AB  - A structural characterization of polysaccharides extracted from the
      aposymbiotically cultured photobiont of the lichen Ramalina gracilis was carried
      out in order to compare them with those previously found in the symbiotic
      thallus. The photobiont was isolated from thallus fragments, following the method
      of Yamamoto, and cultivated in a liquid nutrient medium. Freeze-dried cells were
      defatted, and the polysaccharides extracted successively with water and aq. 10%
      KOH, each at 100 degrees C. After purification, the soluble fractions provided a
      polysaccharide containing a (1-->5)-linked beta-galactofuranosyl backbone,
      substituted in a small proportion at O-6 by beta-Galf units. Amylose was also
      found, as insoluble material obtained on freeze-thawing of the alkaline extract.
      These polysaccharides have not been found in the symbiotic thallus of Ramalina
      gracilis, which contained only water-soluble (isolichenan) and insoluble glucans
      (nigeran and laminaran), and galactomannan. Surprisingly, the galactofuranan has
      similarities with those found in some fungal cell walls.

PMID- 15727841
TI  - Identification of strain specific markers in Bacillus anthracis by random
      amplification of polymorphic DNA.
AB  - Classification and differentiation of Bacillus anthracis isolates by genetic
      markers play an important role in anthrax research. We used a PCR based method-
      Random Amplification of Polymorphic DNA (RAPD)--to identify genetic markers in B.
      anthracis strains. Twenty-five differential genetic markers were identified which
      divided the strains into five different groups. Three selected RAPD-markers were
      cloned and sequenced. The five RAPD-derived genotypes could be defined by
      integration of these three markers. This system offers a simple non-expensive
      method to classify B. anthracis strains in laboratories involved in the research
      of this bacterium.

PMID- 15727842
TI  - Saliva affects the antifungal activity of exogenously added histatin 3 towards
      Candida albicans.
AB  - Antifungal activity of histatin 3 against two Candida albicans clinical isolates
      was determined in assays containing rabbit submandibular gland saliva. Histatin 3
      inhibited the cell growth and germination of both isolates dose-dependently (10
      100 microg ml(-1)) with maximum inhibition occurring after 60 min incubation.
      Adding fresh histatin 3 after 60 min caused further reduction in the viable cell
      count. Higher histatin 3 concentrations (50-100 microg ml(-1)) and prolonged
      exposure to peptide were required to inhibit germination. Histatin 3 was rapidly
      degraded in rabbit submandibular gland saliva and this may explain why fresh
      addition of histatin 3 increases candidacidal activity.

PMID- 15727844
TI  - The gamma-actin encoding gene from the beta-carotene producer Blakeslea trispora.
AB  - We determined the nucleotide sequence of a 4599-bp DNA genomic fragment including
      the gamma-actin encoding gene from Blakeslea trispora, showing an open reading
      frame of 1561 bp interrupted by four introns with fungal consensus splice-site
      junctions. The untranslated regions of the actA gene contain a consensus TATA
      box, a CCAAT motif, a large pyrimidine stretch, and the polyadenylation sequence
      AATAAA. The predicted protein (375 amino acids) revealed high identity to gamma
      actins from fungi (>90%), and gene phylogenies support the grouping of B.
      trispora actin close to those from the majority of the filamentous fungi. actA
      transcript (1.4 kb) level in beta-carotene producing conditions was faintly
      higher than carRA (1.9 kb) and slightly lower than carB (1.8 kb) beta-carotene
      biosynthetic genes. The use of the actA promoter (PactA) for heterologous gene
      expression was ascertained by the transformation of gene fusions with the
      bleomycin resistance gene (bleR) from Streptoalloteichus hindustanus and the
      geneticin resistance marker (aphI) from Tn903, into Escherichia coli and
      Acremonium chrysogenum.

PMID- 15727843
TI  - Antrodia camphorata prevents rat pheochromocytoma cells from serum deprivation
      induced apoptosis.
AB  - Antrodia camphorata (A. camphorata) is a rare medicinal fungus with
      antioxidative, vasorelaxtative, anti-inflammatory and anti-hepatitive effects.
      However, the neuroprotective effect has not been studied. By using serum
      deprivation-induced apoptosis in neuronal-like PC12 cells as a cell stress model,
      we found that A. camphorata is effective in preventing serum-deprived apoptosis.
      Inhibitors of both a serine/threonine kinase and a specific protein kinase A
      (PKA) inhibited the protective effect of A. camphorata, indicating that A.
      camphorata prevents serum-deprived PC12 cell apoptosis through a PKA-dependent
      mechanism. A transcription inhibitor, actinomycin D, and a protein synthesis
      inhibitor, cyclohexamide, both attenuated the protective effect of A. camphorata,
      indicating a requirement for gene expression for protection by A. camphorata. On
      the other hand, A. camphorata also increased phosphorylated CREB, a transcription
      factor, which is H-89-inhibitable in this study, suggesting the possibility that
      A. camphorata prevents serum deprivation-induced PC12 cell apoptosis through a
      PKA/CREB-dependent pathway.

PMID- 15727845
TI  - 2,4,6-Trisubstituted pyrimidine derivatives as pregnancy interceptive agents.
AB  - A series of 2,4,6-trisubstituted pyrimidine derivatives was synthesized and
      evaluated for their in vivo pregnancy interceptive activity in hamsters. Out of
      the 17 compounds synthesized three compounds showed 100% activity at a dose of
      10mg/kg.

PMID- 15727846
TI  - Novel acetylcholinesterase inhibitor as increasing agent on rhythmic bladder
      contractions: SAR of 8-{3-[1-(3-fluorobenzyl)piperidin-4-yl]propanoyl}-1,2,5,6
      tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (TAK-802) and related compounds.
AB  - As part of an on-going investigation to develop an increasing agent on rhythmic
      bladder contractions, 1-aryl-3-(1-benzylpiperidin-4-yl)propanones were
      synthesized and examined as noncarbamate acetylcholinesterase (AChE) inhibitors.
      Among compounds with various aryl groups, 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1
      ij]quinolin-4-one derivative 9c was found to possess a potent AChE inhibition
      activity with an IC(50) value of 1.3nM. The compound 9c increased rhythmic
      bladder contractions in Guinea pigs and rats without affecting the basal
      intravesical pressure, which suggests that 9c may be useful for the treatment of
      voiding dysfunction caused by detrusor underactivity.

PMID- 15727847
TI  - Cooperative lectin recognition of periodical glycoclusters along DNA duplexes:
      alternate hybridization and full hybridization.
AB  - We describe herein the construction of periodically, spatially controlled
      glycoclusters along DNA duplexes and their cooperative lectin recognition. Site
      specifically alpha-mannosylated oligodeoxynucleotide 20-mer (Man-ODN20) was
      synthesized via the phosphoramidite solid-phase synthesis. Alternate
      hybridization of the Man-ODN20 with the half-sliding complementary ODN 20-mer
      (hscODN20) gave an alternately prolonged Man-cluster Man-ODN20/hscODN20. The
      binding of the Man-cluster to FITC-labeled ConA lectin showed sigmoidal
      fluorescence dependency on the concentration of Man-ODN, indicating that some
      mannose residues along the repeating DNA duplex were cooperatively bound to ConA
      (apparent affinity constant: K(af)=2.4 x 10(4)M(-1) and Hill coefficient: n=3.5).
      The duplex of Man-ODN20 with full complementary ODN 20-mer (fcODN20) was little
      bound to ConA. The binding behavior of Man-ODN20/hscODN20 is compared with that
      of the alternately prolonged Gal-cluster Gal-ODN20/hscODN20 previously reported.
      Duplexes 20-mer, 40-mer, and 60-mer presenting one, two, and three periodic
      galactoses were also prepared by full hybridization of 20-mer beta-galactosylated
      oligodeoxynucleotide (Gal-ODN20) with the periodically repeating full
      complementary 20-mer, 40-mer, and 60-mer ODNs. RCA(120) lectin was found to
      little bind the 20-mer and 40-mer duplexes and to bind weakly and non
      cooperatively the 60-mer duplex (K(af)=1.1 x 10(4)M(-1)). The cooperative lectin
      recognition of these glycoclusters in relation with the degree of association
      (DA) of ODN and the numbers of glycosides along the DNA duplex is discussed.

PMID- 15727848
TI  - Design and synthesis of an optimized positional scanning library of peptoids:
      identification of novel multidrug resistance reversal agents.
AB  - Herein is reported the optimized solid-phase synthesis of a library of 5,120
      trimeric N-alkylglycines (peptoids) using the positional scanning format and the
      submonomer strategy. Diversity at the N-terminal position was generated from 20
      commercially available primary amines, whereas 16 primary amines were employed
      for the middle and C-terminal positions of the trimers. Formation of undesirable
      side-products observed in a previous library synthesis (Humet, M. et al. J. Comb.
      Chem. 2003, 5, 597-605) was averted by restricting the use of primary amines
      functionalized with tertiary amino groups to the third amination step. Screening
      of the new library for the identification of chemosensitizers yielded two
      peptoids, compounds 1 and 2, with potent in vitro activity as multidrug
      resistance (MDR) reversal agents. The structures of the lead peptoids are
      consistent with a pharmacophore model generated from the interaction of various
      known inhibitors with the MDR-implicated transmembrane glycoprotein P-gp.

PMID- 15727849
TI  - Design, synthesis, antibacterial and QSAR studies of benzimidazole and imidazole
      chloroaryloxyalkyl derivatives.
AB  - In view of obtaining some potential antibacterial compounds, we have described
      synthesis of some chloroaryloxyalkyl imidazole and benzimidazole derivatives. The
      relevant step in the synthetic sequence was the initial condensation of 4-chloro
      or 2,4-dichlorophenol with 1, n-dibromoalkanes (n=2, 4, 5) to provide compounds
      3a-f in sufficient yields. The subsequent condensation of 3a-f with some
      imidazole derivatives and benzimidazole afforded products 4a-l and 5a-e in good
      yields. Some of compounds 4a-l as well as 5a-e were tested in vitro against
      Salmonella typhi O-901 and Staphylococcus aureus A 15091. Compounds 4a and 4c
      showed considerable bactericidal activities against tested bacteria. Compound 4b
      showed significant activity against S. aureus A 15091 but was inactive against S.
      typhi O-901. Other compounds showed intermediate activities against S. aureus A
      15091 but most of them were inactive against S. typhi O-901. Semiempirical AM1
      calculations showed that negative electrostatic potentials around oxygen of the
      phenoxy and nitrogen of the imidazole moieties have direct effect on the
      antibacterial activity towards S. aureus A 15091. In QSAR analysis, different
      electronic, topologic, functional groups and physicochemical descriptors were
      calculated for each molecule and a three parametric equation was found between
      the logMIC and HOMO energy, hydration energy and number of primary carbon atoms
      of the molecules.

PMID- 15727850
TI  - Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate
      dehydrogenase.
AB  - A series of 2-phenyl quinoline-4-carboxylic acid derivatives related to
      brequinar, an inhibitor of human dihydroorotate dehydrogenase (DHODH), has been
      prepared and evaluated as inhibitors of DHODH from the malaria parasite
      Plasmodium falciparum. Brequinar was essentially inactive against PfDHODH (IC(50)
      880 microM) whereas several members of the series inhibited PfDHODH.
      Unexpectedly, replacement of the carboxylic acid required for brequinar to
      inhibit hDHODH was not essential in the diisopropylamides that inhibited PfDHODH.

PMID- 15727851
TI  - 2,7-Dihydro-3H-pyridazino[5,4,3-kl]acridin-3-one derivatives, novel type of
      cytotoxic agents active on multidrug-resistant cell lines. Synthesis and
      biological evaluation.
AB  - We have earlier postulated that the presence of a pyridazone ring fused with an
      anthracenedione moiety resulted in the analog's ability to overcome multidrug
      resistance of tumor cells [J. Med. Chem.1999, 42, 3494]. High cytotoxic activity
      of obtained anthrapyridazones [Bioorg. Med. Chem.2003, 11, 561] toward the
      resistant cell lines, prompted us to synthesize the similarly modified acridine
      compounds. A series of pyridazinoacridin-3-one derivatives (2b-h) were prepared
      from the reaction of 9-oxo-9,10-dihydroacridine-1-carboxylate with POCl(3),
      followed by addition of the appropriate (alkylamino)alkylhydrazines. In vitro
      cytotoxic activity toward sensitive and resistant leukemia cell lines: L1210,
      K562, K562/DX, HL-60, HL-60/VINC, and HL-60/DX, with various type of multidrug
      resistance (MDR and MRP) was determined. The compounds studied exhibited in
      comparison to the reference cytostatics (DX, MIT) desirable very low resistance
      indexes (RI). Variations have been observed depending upon the substituent and
      the type of drug exporting pump. The cytotoxic activities of examined compounds,
      as well as of model anthrapyridazone derivative PDZ, were lower than those of
      reference drugs (DX, MIT) due to their diminished affinity to DNA.

PMID- 15727852
TI  - Conformational restrictions in ligand binding to the human intestinal di
      /tripeptide transporter: implications for design of hPEPT1 targeted prodrugs.
AB  - The aim of the present study was to develop a computational method aiding the
      design of dipeptidomimetic pro-moieties targeting the human intestinal di
      /tripeptide transporter hPEPT1. First, the conformation in which substrates bind
      to hPEPT1 (the bioactive conformation) was identified by conformational analysis
      and 2D dihedral driving analysis of 15 hPEPT1 substrates, which suggested that
      psi(1) approximately 165 degrees , omega(1) approximately 180 degrees , and
      phi(2) approximately 280 degrees were descriptive of the bioactive conformation.
      Subsequently, the conformational energy required to change the peptide backbone
      conformation (DeltaE(bbone)) from the global energy minimum conformation to the
      identified bioactive conformation was calculated for 20 hPEPT1 targeted model
      prodrugs with known K(i) values. Quantitatively, an inverse linear relationship
      (r(2)=0.81, q(2)=0.80) was obtained between DeltaE(bbone) and log1/K(i), showing
      that DeltaE(bbone) contributes significantly to the experimentally observed
      affinity for hPEPT1 ligands. Qualitatively, the results revealed that compounds
      classified as high affinity ligands (K(i)<0.5 mM) all have a calculated
      DeltaE(bbone)<1 kcal/mol, whereas medium and low-affinity compounds (0.5
      mM<K(i)<15 mM) have DeltaE(bbone) values in the range 1-3 kcal/mol. The findings
      also shed new light on the basis for the experimentally observed
      stereoselectivity of hPEPT1.

PMID- 15727854
TI  - Parallel synthesis and dopamine D3/D2 receptor screening of novel {4-[4-(2
      methoxyphenyl)piperazin-1-yl]butyl}carboxamides.
AB  - We have applied a fast and high-yielding method for the parallel amidation of 4
      [4-(2-methoxyphenyl)piperazin-1-yl]-butylamine yielding analogs of the partial
      dopamine receptor agonist BP 897. Using this amino scaffold prepared in solution
      and polymer-bound carboxylic acid equivalents, we have synthesized a series of
      high affinity dopamine D(3) receptor ligands. The novel compounds were obtained
      in good to excellent yield and purity. Biological evaluation included
      determination of binding affinities at hD(2S) and hD(3) receptor subtypes. From
      the 22 novel structures presented here, compound 4v showed high affinity (K(i)
      (hD(3)) 1.6nM) and a 136-fold preference for the D(3) receptor versus that for
      the D(2) receptor subtype. Our results suggest that this derivatization technique
      is a useful method to speed up structure-activity relationships studies on
      dopamine receptor subtype modulators.

PMID- 15727853
TI  - Inhibition of secretory phospholipase A2. 2-Synthesis and structure-activity
      relationship studies of 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol
      5-one (PMS1062) derivatives specific for group II enzyme.
AB  - We have recently reported the discovery of a series of specific inhibitors of
      human group IIA phospholipase A(2) (hGIIA PLA(2)) to display promising in vitro
      and in vivo properties. Here we describe the influence of different structural
      modifications on the specificity and potency against hGIIA PLA(2) versus porcine
      group IB PLA(2). The SAR results, as well as the logP and pK(a) values of
      oxadiazolone determined in this work, provide important information towards the
      comprehension of the mode of action of this kind of compounds.

PMID- 15727855
TI  - UV-B protective effect of a polyacylated anthocyanin, HBA, in flower petals of
      the blue morning glory, Ipomoea tricolor cv. Heavenly Blue.
AB  - The protective effects of polyacylated anthocyanin, heavenly blue anthocyanin
      (HBA), in blue flower petals of morning glory (Ipomoea tricolor cv. Heavenly
      Blue) against UV-B induced DNA damage were examined. We first clarified the
      concentration of HBA in epidermal vacuoles to be 12mM, and then constructed a UV
      B irradiating apparatus resembling flower petal tissue to assess the screening
      effect of HBA. Monochromatic (280 and 310nm) or broad UV-B induced DNA lesions
      were reduced completely by the HBA filter to the same molecular numbers as those
      in living petal epidermis. However, diluted HBA solution and trisdeacyl HBA did
      not have the same reduction effect. HBA was more tolerant to solar radiation than
      trisdeacyl HBA. These data strongly suggest that polyacylated anthocyanins in
      flower petals can screen harmful UV-B efficiently. This action might be largely
      due to aromatic acyl residues.

PMID- 15727856
TI  - Synthesis and biological activity of fluoroquinolone-pyrrolo[2,1
      c][1,4]benzodiazepine conjugates.
AB  - Fluoroquinolones have been synthesized and linked to DC-81 at C8 position through
      different alkyl chain spacers. These PBD conjugates have exhibited good DNA
      binding affinity, and a representative compound shows promising in vitro
      anticancer activity.

PMID- 15727857
TI  - Synthesis and biological evaluation of new symmetrical derivatives as cytotoxic
      agents and apoptosis inducers.
AB  - Based on the research of less toxic anticancer therapies, we have looked for
      novel compounds with anticancer activity based on a proapoptotic mechanism. The
      described compounds are derivatives of ether, carbamate, urea, amide, or amine.
      Some of the prepared compounds decreased cell viability of various tumor cell
      lines in a time- and dose-dependent manner, and also induced DNA fragmentation,
      which indicated cell apoptosis. The potential antitumoral activity of the
      compounds was evaluated in vitro by examining their cytotoxic effects against
      human mama, colon, and bladder cancer cell lines (MD-MBA-231, HT-29, and T-24).
      Compounds showing cytotoxic activity were subjected to an apoptosis assay. In
      addition, some of the synthesized compounds provoked a rapid and dose-dependent
      increase in the level of caspase-3, an enzyme, which is considered to be one of
      the principal executing caspases in which all of the biochemical routes involved
      in the apoptosis response converge. The most promising compounds, with respect to
      cytotoxicity and apoptosis induction capability, were the 4-nitrophenylcarbamate
      derivative of 2,2'-methylenebis(4-chlorophenyl) 3c, the naphthylurea derivative
      4d, and the n-propylurea derivative 4c, from 4,4'-methylenebisphenyl, all of
      which displayed cytotoxic activity and showed very interesting levels of
      apoptosis. Furthermore, good levels of apoptosis induction were achieved for 3a
      and 4b in the T-24 cell line. Therefore, compounds such as 7b, a pyrido[2,3
      d]pyrimidine derivative, show a significant in vitro cytotoxicity, with IC(50)
      values between 3 and 8 microm in the three cell lines tested. This compound also
      produced a rapid and dose-dependent increase of the caspase-3 level and induced
      apoptosis in HT-29 cells. Other profiles have been found, such as those presented
      by 5c and 7c, which are cytotoxic and apoptotic but do not provoke an increase in
      the level of caspase-3, or those presented by 1c, 1d, and 2a, which are
      cytotoxic, without showing any other activity. The different types of behavior of
      each compound are not necessarily parallel in the three cell lines tested. A
      great number of these compounds of interest show no cytotoxicity in nontumoral
      human cells such as CRL-8799, a nontumoral line of mama. Subsequent modulation of
      these lead structures permits advances in the design of potent cytotoxic and
      proapoptotic anticancer drugs.

PMID- 15727858
TI  - Synthesis, conformational analysis, and biological activity of new analogues of
      thiazole-4-carboxamide adenine dinucleotide (TAD) as IMP dehydrogenase
      inhibitors.
AB  - Thiazole-4-carboxamide adenine dinucleotide (TAD) analogues T-2'-MeAD (1) and T
      3'-MeAD (2) containing, respectively, a methyl group at the ribose 2'-C-, and 3'
      C-position of the adenosine moiety, were prepared as potential selective human
      inosine monophosphate dehydrogenase (IMPDH) type II inhibitors. The synthesis of
      heterodinucleotides was carried out by CDI-catalyzed coupling reaction of
      unprotected 2'-C-methyl- or 3'-C-methyl-adenosine 5'-monophosphate with 2',3'-O
      isopropylidene-tiazofurin 5'-monophosphate, and then deisopropylidenation.
      Biological evaluation of dinucleotides 1 and 2 as inhibitors of recombinant human
      IMPDH type I and type II resulted in a good activity. Inhibition of both
      isoenzymes by T-2'-MeAD and T-3'-MeAD was noncompetitive with respect to NAD
      substrate. Binding of T-3'-MeAD was comparable to that of parent compound TAD,
      while T-2'-MeAD proved to be a weaker inhibitor. However, no significant
      difference was found in inhibition of the IMPDH isoenzymes. T-2'-MeAD and T-3'
      MeAD were found to inhibit the growth of K562 cells (IC(50) 30.7 and 65.0muM,
      respectively).

PMID- 15727859
TI  - Properties and structure-activity studies of cyclic beta-hairpin peptidomimetics
      based on the cationic antimicrobial peptide protegrin I.
AB  - The properties and structure-activity relationships (SAR) of a macrocyclic
      analogue of porcine protegrin I (PG-I) have been investigated. The lead compound,
      having the sequence cyclo-(-Leu-Arg-Leu-Lys-Lys-Arg-Arg-Trp-Lys-Tyr-Arg-Val-d-Pro
      Pro-), shows antimicrobial activity against Gram-positive and -negative bacteria,
      but a much lower haemolytic activity and a much reduced ability to induce dye
      release from phosphatidylcholine/phosphatidylglycerol liposomes, when compared to
      PG-I. The enantiomeric form of the lead peptide shows comparable antimicrobial
      activity, a property shared with other cationic antimicrobial peptides acting on
      cell membranes. SAR studies involving the synthesis and biological profiling of
      over 100 single site substituted analogues, showed that the antimicrobial
      activity was tolerant to a large number of the substitutions tested. Some
      analogues showed slightly improved antimicrobial activities (2-4-fold lowering of
      MICs), whereas other substitutions caused large increases in haemolytic activity
      on human red blood cells.

PMID- 15727860
TI  - 5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones,
      a new series of potent, broad-spectrum non-nucleoside reverse transcriptase
      inhibitors belonging to the DABO family.
AB  - 2-Alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)
      ones (F(2)-NH-DABOs) 4, 5 belonging to the dihydro-alkoxy-benzyl-oxopyrimidine
      (DABO) family and bearing different alkyl- and arylamino side chains at the C(2)
      position of the pyrimidine ring were designed as active against wild type (wt)
      human immunodeficiency virus type 1 (HIV-1) and some relevant HIV-1 mutants.
      Biological evaluation indicated the importance of the further anchor point of
      compounds 4, 5 into the non-nucleoside binding site (NNBS): newly synthesized
      compounds were highly active against both wild type and the Y181C HIV-1 strains.
      In anti-wt HIV-1 assay the potency of amino derivatives did not depend on the
      size or shape of the C(2)-amino side chain, but it associated with the presence
      of one or two methyl groups (one at the pyrimidine C(5)-position and the other at
      the benzylic carbon), being thymine, alpha-methyluracil or alpha-methylthymine
      derivatives almost equally active in reducing wt HIV-1-induced cytopathogenicity
      in MT-4 cells. Against the Y181C mutant strain, 2,6-difluorobenzyl-alpha
      methylthymine derivatives 4d, 5h'-n' showed the highest potency and selectivity
      among tested compounds, both a properly sized C(2)-NH side chain and the presence
      of two methyl groups (at C(5) and benzylic positions) being crucial for high
      antiviral action.

PMID- 15727861
TI  - Synthesis and biological evaluation of 2-aminothiazoles and their amide
      derivatives on human adenosine receptors. Lack of effect of 2-aminothiazoles as
      allosteric enhancers.
AB  - A number of 2-aminothiazoles (2a-e) and their amide derivatives (4-10) were
      prepared. The 2-aminothiazoles themselves were tested as allosteric enhancers of
      agonist binding to human adenosine A(1) receptors. In a variety of experimental
      set-ups the compounds did not show any such effect, in contrast to earlier
      findings by another research group. Subsequently the 2-aminothiazoles were used
      as intermediates in the synthesis of a number of amide derivatives of either
      aromatic (4-6) or aliphatic nature (7-10). Some of the compounds emerged as
      moderately active antagonists on human adenosine A(1) and/or A(2A) receptors with
      lower or negligible potency at adenosine A(3) receptors.

PMID- 15727862
TI  - Fluorosubstitution and 7-alkylation as prospective modifications of biologically
      active 6-aryl derivatives of tricyclic acyclovir and ganciclovir analogues.
AB  - A series of fluorine containing tricyclic analogues of acyclovir (ACV, 1) and
      ganciclovir (GCV, 2) were synthesized and evaluated for their activity against
      herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and cytostatic activity
      against HSV-1 thymidine kinase (TK) gene-transduced human osteosarcoma tumour
      cells. It was found that fluorine substitution reduced the antiviral activity,
      but most of the new compounds were pronounced cytostatic agents with potency and
      selectivity similar to those of parental ACV and GCV. Compounds 12, 13 and 16
      seem to be promising as labeled substrates for (19)F NMR studies of the HSV TK
      ligand interaction and/or monitoring of their metabolites in cells expressing HSV
      TK.

PMID- 15727863
TI  - New naphthylcombretastatins. Modifications on the ethylene bridge.
AB  - Compounds with three aromatic systems, carrying a 2-naphthalene and a 3,4,5
      trimethoxyphenyl moieties bonded to five-membered, six-membered or fused
      heterocycles display potent cytotoxic effect and inhibition of tubulin
      polymerization, in agreement with their structural similarity to combretastatins
      and their heterocyclic analogues.

PMID- 15727864
TI  - A novel method of estimation of lipophilicity using distance-based topological
      indices: dominating role of equalized electronegativity.
AB  - Attempt is made to propose yet another method of estimating lipophilicity of a
      heterogeneous set of 223 compounds. The method is based on the use of equalized
      electronegativity along with topological indices. It was observed that excellent
      results are obtained in multiparametric regression upon introduction of indicator
      parameters. The results are discussed critically on the basis various statistical
      parameters.

PMID- 15727866
TI  - Heterocyclic inhibitors of dihydrodipicolinate synthase are not competitive.
AB  - A series of piperidine- and pyridine-2,6-dicarboxylate derivatives has been
      evaluated as potential inhibitors of dihydrodipicolinate synthase (DHDPS). The
      compounds were designed with oxygen functionality at the C-4 position in order to
      mimic the putative enzyme product HTHDP. Most compounds displayed weak-moderate
      inhibition of DHDPS. Additionally, the most potent inhibitors were shown not to
      be competitive, indicating they do not bind at the active site. Discrepancies
      between the two common assay systems-the imidazole assay and the coupled assay
      were observed which are attributed to inherent problems in the imidazole assay,
      leading to artefactually low K(i) measurements.

PMID- 15727865
TI  - Molecular docking and 3D-QSAR studies on the binding mechanism of statine-based
      peptidomimetics with beta-secretase.
AB  - beta-Secretase is an important protease in the pathogenesis of Alzheimer's
      disease. Some statine-based peptidomimetics show inhibitory activities to the
      beta-secretase. To explore the inhibitory mechanism, molecular docking and three
      dimensional quantitative structure-activity relationship (3D-QSAR) studies on
      these analogues were performed. The Lamarckian Genetic Algorithm (LGA) was
      applied to locate the binding orientations and conformations of the
      peptidomimetics with the beta-secretase. A good correlation between the
      calculated binding free energies and the experimental inhibitory activities
      suggests that the identified binding conformations of these potential inhibitors
      are reliable. Based on the binding conformations, highly predictive 3D-QSAR
      models were developed with q(2) values of 0.582 and 0.622 for CoMFA and CoMSIA,
      respectively. The predictive abilities of these models were validated by some
      compounds that were not included in the training set. Furthermore, the 3D-QSAR
      models were mapped back to the binding site of the beta-secretase, to get a
      better understanding of vital interactions between the statine-based
      peptidomimetics and the protease. Both the CoMFA and the CoMSIA field
      distributions are in well agreement with the structural characteristics of the
      binding groove of the beta-secretase. Therefore, the final 3D-QSAR models and the
      information of the inhibitor-enzyme interaction would be useful in developing new
      drug leads against Alzheimer's disease.

PMID- 15727867
TI  - Development of alpha-keto-based inhibitors of cruzain, a cysteine protease
      implicated in Chagas disease.
AB  - Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas
      disease, a major cause of cardiovascular disease in many Latin American
      countries. There is an urgent need to develop an improved therapy due to the
      toxicity of existing drugs and emerging drug resistance. Cruzain, the primary
      cysteine protease of T. cruzi, is essential for the survival of the parasite in
      host cells and therefore is an important target for the development of inhibitors
      as potential therapeutics. A novel series of alpha-ketoamide-, alpha-ketoacid-,
      alpha-ketoester-, and aldehyde-based inhibitors of cruzain has been developed.
      The inhibitors were identified by screening protease targeted small molecule
      libraries and systematically optimizing the P1, P2, P3, and P1' residues using
      specific structure-guided methods. A total of 20 compounds displayed picomolar
      potency in in vitro assays and three inhibitors representing different alpha-keto
      based inhibitor scaffolds demonstrated anti-trypanosomal activity in cell
      culture. A 2.3A crystallographic structure of cruzain bound with one of the alpha
      ketoester analogs is also reported. The structure and kinetic assay data
      illustrate the covalent binding, reversible inhibition mechanism of the
      inhibitor. Information on the compounds reported here will be useful in the
      development of new lead compounds as potential therapeutic agents for the
      treatment of Chagas disease and as biological probes to study the role that
      cruzain plays in the pathology. This study also demonstrates the validity of
      structure-guided approaches to focused library design and lead compound
      optimization.

PMID- 15727868
TI  - Design and synthesis of new antimalarial agents from 4-aminoquinoline.
AB  - This study describes the synthesis of new 4-aminoquinoline derivatives and
      evaluation of their activity against a chloroquine sensitive strain of P.
      falciparum in vitro and chloroquine resistant N-67 strain of P. yoelii in vivo.
      All the analogues were found to form strong complex with hematin and inhibit the
      beta-hematin formation in vitro. These results suggest that these compounds act
      on heme polymerization target.

PMID- 15727869
TI  - Inhibitory effects of 2-substituted-1-naphthol derivatives on cyclooxygenase I
      and II.
AB  - Naphthol derivatives, 2-(3'-hydroxypropyl)-naphthalen-1-ol (2), 2-(3'-hydroxy-2'
      methylpropyl)-naphthalen-1-ol (3) and 2-(3'-hydroxy-2',2'-dimethylpropyl)
      naphthalen-1-ol (7) were synthesized and already reported by our group. Therefore
      in this paper we described further synthesis of their ether derivatives, 3-(1
      methoxy-naphthalen-2-yl)-propan-1-ol (4), 3-(1-methoxy-naphthalen-2-yl)-2methyl
      propan-1-ol (5), 3-(1-methoxy-naphthalen-2-yl)-2,2-dimethyl-propan-1-ol (8), 2-(3
      methoxy-propyl)-naphthalen-1-ol (10) and 2-(3-methoxy-2,2-dimethyl-propyl)
      naphthalen-1-ol (13). Compounds 4, 5 and 8 were prepared by methylation of
      compounds 2, 3 and 7, respectively while compounds 10 and 13 were prepared in
      good yield from naphthols 2 and 7, respectively. When tested for inhibitory
      activity, five compounds (2, 3, 7, 10 and 13) showed preferential inhibition of
      COX-2 over COX-1, while compounds 4, 5 and 8 lacked inhibitory effect on either
      the COX-1 or COX-2 isozyme. The structure-activity relationships of these
      naphthols analyzed by docking experiments, indicated that the presence of
      hydroxyl group at C-1 position on the naphthalene nucleus enhanced the anti
      inflammatory activity towards COX-2 via hydrogen bonding to the COX-2 Val 523
      side chain. When this hydroxyl group was replaced by methoxy group, there was no
      inhibition. C-2' Dimethyl substituents on the propyl chain also increased the
      inhibitory activity. All active compounds have the C-1 hydroxyl group aligned so
      as to form hydrogen bond with Val 523. The results provide a model for the
      binding of the naphthol derivatives to COX-2 and facilitate the design of more
      potent or selective analogs prior to synthesis.

PMID- 15727870
TI  - Structure-activity study of epi-gallocatechin gallate (EGCG) analogs as
      proteasome inhibitors.
AB  - The structure-activity relationship of a number of synthetic green tea polyphenol
      analogs involving modifications of A ring and B ring of epi-gallocatechin gallate
      (EGCG) as proteasome inhibitors has been examined. It was found that in B ring, a
      decrease in the number of OH groups led to decreased potency. Introduction of a
      hydrophobic benzyl group into the 8 position of A ring did not significantly
      affect the proteasome-inhibitory potency.

PMID- 15727871
TI  - Dipeptide alcohol-based inhibitors of eukaryotic DNA polymerase alpha.
AB  - We reported previously that a novel dipeptide alcohol, l-homoserylaminoethanol
      (Hse-Gly-ol), is a selective inhibitor of eukaryotic DNA polymerase epsilon (pol
      epsilon) [Bioorg. Med. Chem.2004, 12, 957-962]. The discovery suggests that the
      dipeptide structure could be a chemical frame for a DNA polymerase inhibitor.
      Therefore, we chemically synthesized 27 different species of dipeptide alcohols,
      and tested this inhibitory capability. Compound 6 (l-aspartylaminoethanol, Asp
      Gly-ol) was found to be the strongest pol alpha inhibitor. Compound 6 did not
      influence the activities of other replicative DNA polymerases such as delta and
      epsilon, and had no effect on the activities of prokaryotic DNA polymerases, nor
      DNA metabolic enzymes such as human immunodeficiency virus type 1 reverse
      transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. The inhibitory
      effect of compound 6 on pol alpha was dose-dependent, and 50% inhibition was
      observed at a concentration of 33.5 microM. Compound 6-induced inhibition of pol
      alpha activity was non-competitive with both the DNA template-primer and the dNTP
      substrate. This is the first report on a water-soluble pol alpha-specific
      inhibitor, sought for precise biochemical studies of pol alpha. The relationships
      between the structures of dipeptide alcohols and the inhibition of eukaryotic DNA
      polymerases are discussed.

PMID- 15727872
TI  - A physically interpretable quantum-theoretic QSAR for some carbonic anhydrase
      inhibitors with diverse aromatic rings, obtained by a new QSAR procedure.
AB  - A QSAR based almost entirely on quantum theoretically calculated descriptors has
      been developed for a large and heterogeneous group of aromatic and heteroaromatic
      carbonic anhydrase inhibitors, using orbital energies, nodal angles, atomic
      charges, and some other intuitively appealing descriptors. Most calculations have
      been done at the B3LYP/6-31G* level of theory. For the first time we have treated
      five-membered rings by the same means that we have used for benzene rings in the
      past. Our flip regression technique has been expanded to encompass automatic
      variable selection. The statistical quality of the results, while not equal to
      those we have had with benzene derivatives, is very good considering the
      noncongeneric nature of the compounds. The most significant correlation was with
      charge on the atoms of the sulfonamide group, followed by the nodal orientation
      and the solvation energy calculated by COSMO and the charge polarization of the
      molecule calculated as the mean absolute Mulliken charge over all atoms.

PMID- 15727873
TI  - Synthesis and antiamoebic activities of 1-N-substituted cyclised pyrazoline
      analogues of thiosemicarbazones.
AB  - A series of 21 new 1-N-substituted cyclised pyrazoline analogues of
      thiosemicarbazones were synthesised by cyclisation of Mannich bases with
      thiosemicarbazides of variegated nature. The chemical structures of the compounds
      were proved by UV, IR, (1)H NMR, (13)C NMR spectroscopic data and elemental
      analyses. The antiamoebic activities of these compounds were evaluated by
      microdilution method against HM1:1MSS strain of Entamoeba histolytica. It was
      found that 3-chloro and 3-bromo substituents on the phenyl ring at position 3 of
      the pyrazoline ring enhanced the antiamoebic activity as compared to
      unsubstituted phenyl ring. Compounds 15, 17, 18, 20 and 21 showed less IC(50)
      value than metronidazole. Moreover, compound 21 have shown the most promising
      antiamoebic activity (IC(50)=0.6 microM vs IC(50)=1.8 microM of metronidazole).

PMID- 15727874
TI  - Oxathiolene oxide synthesis via chelation-controlled addition of organometallic
      reagents to alkynols followed by addition of sulfur electrophiles and evaluation
      of oxathiolene oxides as anticarcinogenic enzyme inducers.
AB  - A number of alkynols have been prepared by Sonogashira coupling of propargyl
      alcohol to aromatic halides. Chelation-controlled addition of organometallic
      nucleophiles to these alkynols was then effected followed by the addition of the
      sulfur electrophiles, sulfur dioxide or thionyl chloride. This methodology was
      used to prepare a number of oxathiolene oxides, which have been screened as NQO1
      (quinone oxidoreductase) inducers.

PMID- 15727875
TI  - Core-modified porphyrins. Part 4: Steric effects on photophysical and biological
      properties in vitro.
AB  - 21,23-Dithiaporphyrins (2-10) were designed and prepared as analogues of 5,20
      diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin (1) to
      examine the impact of steric bulk at the 5- and 20-meso positions as well as the
      impact of symmetry. Changes at the meso positions had minimal impact on the UV
      vis-near-IR absorption spectra, quantum yields for the generation of singlet
      oxygen, and quantum yields for fluorescence and some impact on values of the
      octanol/water partition coefficient. Of the compounds 1-10, 5-phenyl-20-(2
      thienyl)-10,15-bis-(4-carboxylatomethoxy-phenyl)-21,23-dithiaporphyrin (3) showed
      the greatest phototoxicity toward cultured R3230AC cells, with 68% cell kill at 1
      x 10(-7)M and irradiation with 5J cm(-2) of 350-750 nm light. Results in this
      study suggest that smaller substituents on the meso ring and less symmetrical
      compounds are more effective as photosensitizers than compounds with two bulky
      substituents at adjoining meso sites and a higher symmetry. The mitochondria
      appear to be involved in the process of phototoxicity as determined by the
      inhibition of whole cell cytochrome c oxidase activity in cells treated with 3
      and light. No impact upon mitochondrial cytochrome c oxidase activity was
      observed in cells treated with 3 and no light. Fluorescence microscopy studies
      suggest that the mitochondria are not initial sites of accumulation of 3.

PMID- 15727876
TI  - 1H NMR studies of homo and mixed ligand complexes of Tl+ ion with several
      polyazamacrocycles.
AB  - Proton NMR was used as a probe to study the interaction of the Tl(+) ion with 9
      18-membered macromonocyclic tri-, tetra-, and hexaamines in dimethylformamide
      (DMF) solution. A study of proton chemical shift of ligands as a function of
      Tl(+) ion to ligand mole ratio revealed that the complexation reactions occur in
      a stepwise manner. Formation of a 1:1 complex is followed by the addition of a
      second complexant molecule to form a homo-sandwich complex for triazamacrocycle
      ligands and a mixed ligand complex in the case of hexamethylhexacyclen (HMHCY)
      and 1,4,7-triazacyclononane ([9]aneN(3)). The formation constants of resulting
      1:1 and 1:2 (homo and mixed ligand sandwich) complexes in DMF solution were
      evaluated from computer fitting of the chemical shift-mole ratio data. The mixed
      ligand complexes may be more stable than the parent complex in which both ligands
      are the same. The influence of cavity size and substitution of methyl groups on
      nitrogen atoms of the macrocyclic ring the stability of the resulting complexes
      is discussed. The geometries of the tri- and tetraazamacrocycle ligands and their
      Tl(+) ion complexes were optimized by an ab initio method, and the calculated
      binding energies of resulting complexes were compared. Both the experimental and
      theoretical studies revealed that, in the presence of methyl groups, the
      stability of triazamacrocycle complexes with Tl(+) ion was decreased.

PMID- 15727877
TI  - 3-Aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione for
      circumvention of anticancer drug resistance.
AB  - A series of 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10
      dione was synthesized by Mannich reaction or by the transamination of 3
      dimethylaminomethyl 4,11-dihydroxy- or 4,11-dimethoxynaphtho[2,3-f]indole-5,10
      dione. The potency of novel derivatives was tested on a National Cancer Institute
      panel of 60 human tumor cell lines as well as in cells with genetically defined
      determinants of cytotoxic drug resistance, P-glycoprotein (Pgp) expression, and
      p53 inactivation. Mannich derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10
      dione with an additional amino function in their side chain, demonstrated equal
      cytotoxicity against the parental K562 leukemia cells and their Pgp-positive
      subline, whereas the latter showed approximately 7-fold resistance to adriamycin,
      a Pgp transported drug. 3-(1-Piperazinyl)methyl and 3-(quinuclidin-3
      yl)aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione
      killed HCT116 colon carcinoma cells (carrying wild type p53) and their p53-null
      variant within the similar range of concentrations. We conclude that Mannich
      modification of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione, especially when
      cyclic diamine (e.g., piperazine, quinuclidine) is used, confers an important
      feature to the resulting compounds, namely, the potency for tumor cells otherwise
      resistant to a variety of anticancer drugs.

PMID- 15727878
TI  - 1-Aryl-4-(4-succinimidobutyl)piperazines and their conformationally constrained
      analogues: synthesis, binding to serotonin (5-HT1A, 5-HT2A, 5-HT7), alpha1
      adrenergic, and dopaminergic D2 receptors, and in vivo 5-HT1A functional
      characteristics.
AB  - Starting with the structure of potent 5-HT(1A) ligands, that is, MM77 [1-(2
      methoxyphenyl)-4-(4-succinimidobutyl)piperazine, 4] and its constrained version 5
      (MP349), previously obtained in our laboratory, a series of their direct
      analogues with differently substituted aromatic ring (R=H, m-Cl, m-CF(3), m
      OCH(3), p-OCH(3)) were synthesized. The flexible and the corresponding 1e,4e
      disubstituted cyclohexane derivatives were designed in order to investigate the
      influence of rigidification on 5-HT(1A) affinity, selectivity for 5-HT(2A), 5
      HT(7), D(1), and D(2) binding sites and functional profile at pre- and
      postsynaptic 5-HT(1A) receptors. The new compounds 19-25 were found to be highly
      active 5-HT(1A) receptor ligands (K(i)=4-44 nM) whereas their affinity for other
      receptors was: either significantly decreased after rigidification (5-HT(7)), or
      controlled by substituents in the aromatic ring (alpha(1)), or influenced by both
      those structural modifications (5-HT(2A)), or very low (D(2), K(i)=5.3-31
      microM). Since a distinct disfavor towards rigid compounds was observed for 5
      HT(7) receptors only, it seems that the bioactive conformation of chain
      derivatives at those sites should differ from the extended one. Several in vivo
      models were used to asses functional activity of 19-25 at pre- (hypothermia in
      mice) and postsynaptic 5-HT(1A) receptors (lower lip retraction in rats and
      serotonin syndrome in reserpinized rats). Unlike the parent antagonists 4 and 5,
      all the new derivatives tested were classified as partial agonists with different
      potency, however, similar effects were observed within pairs (flexible and rigid)
      of the analogues. The obtained results indicated that substitution in the
      aromatic ring, but not spacer rigidification, controls the 5-HT(1A) functional
      activity of the investigated compounds. Moreover, an o-methoxy substituent in the
      structure of 5 seems to be necessary for its full antagonistic properties. Of all
      the new compounds studied, trans-4-(4-succinimidocyclohexyl)-1-(3
      trifluoromethylphenyl)piperazine 24 was the most potent 5-HT(1A) receptor ligand
      in vitro (K(i)=4 nM) and in vivo, with at least 100-fold selectivity for the
      other receptors tested.

PMID- 15727879
TI  - Structure-activity relationship for aryl and heteroaryl boronic acid inhibitors
      of hormone-sensitive lipase.
AB  - A range of aryl and heteroaryl boronic acids were tested for their in vitro
      hormone-sensitive lipase inhibitory properties. (2-Benzyloxy-5
      fluorophenyl)boronic acid, (2-benzyloxy-5-chlorophenyl)boronic acid and 5
      bromothiophene-2-boronic acid were found to be the most potent HSL inhibitors
      with IC(50) values of 140, 17 and 350 nM, respectively.

PMID- 15727880
TI  - General synthesis and biological evaluation of alpha-1-C-substituted derivatives
      of fagomine (2-deoxynojirimycin-alpha-C-glycosides).
AB  - A general synthesis of alpha-1-C-substituted derivatives of fagomine (2
      deoxynojirimycin-alpha-C-glycosides) by ring-opening reactions of an aziridine
      with various heteroatomic nucleophiles, including thiol, amine, alcohol,
      carboxylate and phosphate, is described. The nine-step reaction sequence
      proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological
      evaluation of alpha-1-C-substituted derivatives of fagomine, of the 2-deoxy
      analog of alpha-homonojirimycin 19 and its 1,N-anhydro derivative 22 as
      glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found
      to display no inhibitory activity towards glycogen phosphorylase b and
      phosphoglucomutase.

PMID- 15727881
TI  - Antitumor agents 243. Syntheses and cytotoxicity of desmosdumotin C derivatives.
AB  - New analogs of desmosdumotin C (1), in which other aromatic rings replaced the
      terminal phenyl group and the A-ring was modified, were synthesized. Compounds 2
      9, 13, and 16 were evaluated in vitro against human tumor cell replication. The 4
      bromophenyl analog (2) showed potent cytotoxic activity in four different tumor
      cell lines.

PMID- 15727882
TI  - Comparative molecular similarity indices analysis (CoMSIA) studies of 1,2
      naphthoquinone derivatives as PTP1B inhibitors.
AB  - Protein tyrosine phosphatase-1B (PTP1B) has been demonstrated to play a key role
      in the negative signalling pathway of insulin. Potent and orally active PTP1B
      inhibitors are considered to be promising pharmacological agents for the
      treatment of type-2 diabetes and resistance to weight gain. CoMSIA studies have
      been preformed on 1,2-naphthoquinone derivatives that are reported to be
      potential non-peptidic inhibitors of PTP1B. For the selection of dataset to
      develop the model, the reported molecules were subjected to property filters and
      segregated into training and test set. As the crystal structure of PTP1B
      naphthoquinone derivative is not known, the most active molecule was subjected to
      simulated annealing dynamics method and the lowest energy conformer was
      reminimised and considered as the bioactive conformation. Database-inertial
      alignment was followed for aligning the molecules. Different CoMSIA models were
      built to get the best related field.

PMID- 15727883
TI  - Abnormalities identified in the knees of asymptomatic volunteers using peripheral
      magnetic resonance imaging.
AB  - OBJECTIVE: To estimate the prevalence of bone and soft tissue abnormalities in
      asymptomatic knees using peripheral magnetic resonance imaging (pMRI) and to
      examine the relationship between these abnormalities and Kellgren-Lawrence (K-L)
      graded X-rays. METHOD: Volunteers (20-68 years) with no history of knee pain,
      injury or bone or joint disease were recruited. Individuals underwent a single
      MRI scan and radiograph of their non-dominant knee. pMR images were acquired in
      sagittal plane using a 3-D gradient-echo protocol. Two radiologists graded the
      presence and severity of cartilage degeneration, osteophytosis, meniscal and
      ligamentous abnormalities, bone marrow edema and subchondral cysts. X-rays were
      acquired using a fixed-flexion technique and graded using the K-L scale. RESULTS:
      Forty-four individuals, mean age (SD) 41.1 (14.2) years, participated. K-L
      grading of X-rays revealed 29 individuals were grade 0, 12 were grade 1 and 3
      were grade 2. Five individuals showed evidence of cartilage lesions, the femoral
      trochlea, medial femur and patella being those regions most commonly affected.
      Twelve individuals (27.3%) showed evidence of osteophytosis, nine of whom did not
      show evidence on X-ray. Forty-three individuals showed evidence of at least one
      meniscal abnormality while 27 individuals (61.4%) had abnormalities in at least
      three of the four regions of the knee. CONCLUSION: Our results suggest that
      osteophytes may be more prevalent in this population than radiographic data
      suggests due to the limitations of two-dimensional imaging. Meniscal degeneration
      or tears, a risk factor for knee osteoarthritis, are highly prevalent in
      asymptomatic individuals with the medial anterior and posterior horns being the
      most commonly affected regions.

PMID- 15727884
TI  - Reliability of diffraction enhanced imaging for assessment of cartilage lesions,
      ex vivo.
AB  - OBJECTIVE: The assessment of articular cartilage integrity is of value for the
      detection of early degenerative joint disease in both the clinical and the
      research settings. It was the purpose of this study to determine the accuracy and
      reliability of identifying articular cartilage defects through Diffraction
      Enhanced Imaging (DEI), a high contrast radiographic imaging technique. DEI
      provides two new sources of image contrast to radiography: refraction and scatter
      rejection, besides the absorption of conventional radiography. DESIGN: Cadaveric
      tali were DEI imaged in the anterior-posterior position at the National
      Synchrotron Light Source. Two independent observers provided gross score
      evaluations (on a five point scale) of the trochlear surfaces. The DEI image of
      each trochlear surface was then graded (on a five point scale) by two additional
      independent observers who were blinded with regard to the gross evaluation of the
      articular surfaces. Inter-observer agreement for DEI grades was assessed with the
      weighted kappa statistic. Correlation of diffraction enhanced image score to the
      gross score was assessed with Spearman correlation coefficient. RESULTS: The
      defects of articular cartilage of talar trochleae could be visualized through
      DEI. The Spearman correlation of gross grades with DEI grades on the 165 talar
      regions for observers 1 and 2 were 0.91 and 0.91, respectively. The overall
      weighted kappa value for inter-observer agreement was 0.93, thus considered high
      agreement. CONCLUSIONS: DEI is accurate and reliable for detection of articular
      cartilage defects ex vivo. Even early stages of degeneration of cartilage can be
      visualized with this high contrast technique. Future studies will focus on the
      application of DEI to the identification of such lesions in vivo.

PMID- 15727885
TI  - Knee cartilage defects: association with early radiographic osteoarthritis,
      decreased cartilage volume, increased joint surface area and type II collagen
      breakdown.
AB  - OBJECTIVE: To generate hypotheses regarding the associations between knee
      cartilage defects and knee radiographic osteoarthritis (ROA), cartilage volume,
      bone size and type II collagen breakdown in adults. METHODS: A cross-sectional
      convenience sample of 372 male and female subjects (mean age 45 years, range 26
      61) was studied. Knee cartilage defect score (0-4) and prevalence (a defect score
      of > or =2), cartilage volume, and bone surface area were determined using T1
      weighted fat saturation MRI. Urinary levels of C-terminal crosslinking
      telopeptide of type II collagen (U-CTX-II) were measured by enzyme-linked
      immunosorbent assay. Height, weight and ROA were measured by standard protocols.
      RESULTS: In multivariate analysis, the severity and prevalence of knee cartilage
      defects were significantly and independently associated with tibiofemoral
      osteophytes (regression coefficient (beta): +0.86 to +1.31/unit, odds ratio (OR):
      2.97-3.68/unit, all P<0.05 with the exception of OR in lateral tibiofemoral
      compartment) and tibial bone area (beta: +0.11 to +0.25/cm2; OR: 1.33-1.58/cm2,
      all P<0.01). Knee cartilage defects were inconsistently associated with joint
      space narrowing after adjustment for osteophytes but consistently with knee
      cartilage volume (beta: -0.27 to -0.70/ml; OR: 0.16-0.56/ml, all P<0.01 except
      for OR at lateral tibial cartilage site P=0.06). Lastly, knee cartilage defect
      severity was significantly associated with U-CTX-II (Partial r=+0.18, P<0.001 for
      total cartilage defect score). CONCLUSION: Osteophytes and increasing knee bone
      size may be causally related to knee cartilage defects. Furthermore, knee
      cartilage defects may result in increased cartilage breakdown leading to
      decreased cartilage volume and joint space narrowing suggesting an important role
      for knee cartilage defects in early knee OA.

PMID- 15727886
TI  - Celecoxib improves the efficiency of the locomotor mechanism in patients with
      knee osteoarthritis. A randomised, placebo, double-blind and cross-over trial.
AB  - OBJECTIVE: To compare the effect of celecoxib vs placebo treatment on clinical
      and gait variables in knee osteoarthritis (OA) patients; focusing on the
      efficiency of the locomotor mechanism. METHODS:  STUDY DESIGN: A prospective,
      randomised, double-blind placebo-controlled trial. PATIENTS: Eight adult patients
      with painful OA of the knee. OUTCOME MEASURES: Clinical assessment included knee
      pain assessed by the visual analogue scale, range of knee motion assessed by
      goniometer, and locomotor function status assessed by a Knee Score Scale. Gait
      was assessed by means of instrumented analysis including synchronous kinematic,
      dynamic, electromyographic, and energetic recordings. STATISTICAL ANALYSIS: The
      effect of treatment on the primary variable, the efficiency of the locomotor
      mechanism, and on secondary clinical and gait variables was assessed by the Hills
      and Armitage non-parametric approach. RESULTS: Celecoxib treatment improved the
      efficiency of the locomotor mechanism significantly. Among the secondary outcome
      measures assessed, celecoxib treatment improved walking cadence and reduced the
      knee pain significantly. CONCLUSION: This study shows that celecoxib is effective
      in improving locomotor function and pain in patients with knee OA.

PMID- 15727887
TI  - The association of radiographic foot osteoarthritis and radiographic
      osteoarthritis at other sites.
AB  - OBJECTIVE: To quantify the association between radiographic foot osteoarthritis
      (OA) and radiographic OA at four joints: second distal interphalangeal (DIP),
      third proximal interphalangeal (PIP), first carpometacarpal (CMC), and the knee.
      METHODS: Data collected for the Clearwater Osteoarthritis Study (COS) were
      analyzed (N=3436). The study outcome was first metatarso-phalangeal joint (first
      MTP) OA status. The predictor variables were second DIP, third PIP, first CMC,
      and knee OA. The Kellgren and Lawrence scale determined OA status. The strength
      of the association between foot OA and other sites was further explored by
      unilateral and bilateral categories. RESULTS: For both genders, we found a
      significant, positive relationship between grade 2+ foot OA and second DIP, third
      PIP, first CMC, and knee OA. This relationship maintained its significance after
      adjustment for age, body mass index, and occupational history. Adjusted odds
      ratios ranged from 3.2 for the second DIP joint (P<0.0001) to 3.7 for the knee
      joint (P<0.0001). Relative to unilateral joint disease, co-existing bilateral
      disease yielded a significantly elevated risk for foot OA for all joints
      examined. While other studies have not specifically examined co-occurrence with
      foot OA, our findings are consistent with results from related studies.
      CONCLUSIONS: There is a dearth of studies exploring foot OA. Our findings support
      the theory of a systemic etiology involved in the development of OA. Future
      epidemiological studies that further distinguish the relationship between OA at
      differing sites will provide an enhanced ability to describe the respective
      influences of mechanical and systemic factors in the development of this disease.

PMID- 15727888
TI  - Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease
      modifying activity.
AB  - OBJECTIVE: Although available nonsurgical pharmacotherapies for treatment of
      osteoarthritis (OA) are considered to be solely symptom-modifying agents, recent
      advances have been made in the search for agents that may modify disease
      progression. Intra-articular hyaluronan (HA) therapy is one symptom-modifying
      approach that has been found to be safe and effective for reducing pain due to OA
      of the knee. Presented here is a review of the evidence that HAs may also modify
      the rate of OA disease progression in addition to providing symptomatic efficacy.
      DESIGN: A review of the literature based on a MEDLINE search through June 2004,
      using the terms HA, sodium hyaluronate, hyaluronic acid, hylan, hylan G-F 20, OA,
      disease modification, structure modifying and joint structure. RESULTS: Evidence
      for disease-modifying activity of HAs stems from 1) the complex biochemical
      effects of HAs in the synovium and extracellular matrix of the articular
      cartilage, including interactions between exogenously administered HA and
      articular cartilage, subchondral bone, matrix proteoglycans, and collagens; 2)
      the effects of HA administration in animal models of OA, including total or
      partial meniscectomy and anterior cruciate ligament transectomy; 3) results of
      clinical trials using one HA, Hyalgan (sodium hyaluronate, molecular weight 500
      730 kDa) that evaluated structural outcomes, such as joint-space width,
      chondrocyte density and vitality, and arthroscopic evaluation of chondropathy.
      DISCUSSION: Growing preclinical and clinical evidence supports the notion that,
      in addition to relieving the symptoms of OA, HAs also modify the structure of the
      diseased joint and the rate of OA disease progression, at least early in the
      evolution of the disease process.

PMID- 15727889
TI  - Characterizing osteochondrosis in the dog: potential roles for matrix
      metalloproteinases and mechanical load in pathogenesis and disease progression.
AB  - OBJECTIVE: To address possible roles of matrix metalloproteinases (MMPs) and
      mechanical stress in the pathogenesis of osteochondrosis (OC). METHODS: Naturally
      occurring canine OC lesions (n=50) were immunohistochemically analyzed for MMP-1,
      -3, and -13, and normal canine articular cartilage explants (n=6) cultured under
      0-, 2-, or 4-MPa compressive loads (0.1 Hz, 20 min every 8 h up to 12 days) were
      compared to OC samples (n=4) biochemically and molecularly. RESULTS: MMP-1 and -3
      immunoreactivities were readily detected in both OC samples and control tissues
      obtained from age-matched dogs (n=11) whereas MMP-13 was only detectable in OC
      samples. MMP-13 gene expression as determined by real-time reverse transcription
      polymerase chain reaction was elevated in OC samples and cartilage explants
      cultured without mechanical stimuli (0 MPa groups) compared to normal cartilage
      (day 0 controls). Glycosaminoglycan content (per weight) in cartilage explants
      cultured under no load was significantly (P<0.05) lower on day 12 than in the day
      0 controls. Gene expression levels of aggrecan and type II collagen in OC samples
      were lower than those in the day 0 controls. High levels of aggrecan and collagen
      II expression were seen in the 2 MPa groups. CONCLUSIONS: These findings imply
      that impaired biochemical characteristics in OC-affected cartilage may be
      attributable to decreased extracellular matrix production that may stem from
      disruption of normal weight bearing forces.

PMID- 15727890
TI  - Long-term periarticular bone adaptation in a feline knee injury model for post
      traumatic experimental osteoarthritis.
AB  - OBJECTIVES: This study investigates the long-term changes of the periarticular
      bone, including cancellous bone and the subchondral plate, in an anterior
      cruciate ligament (ACL)-transected cat for post-traumatic osteoarthritis (OA).
      These periarticular bone changes are related to the health of all knee tissues
      including articular cartilage degeneration and may be a key component of
      osteoarthritic development. METHODS: Thirteen cats (mean mass 4.9+/-1.9 kg) were
      divided into three experimental groups: (1) normal controls, (2) 16 week, and (3)
      5 year post unilateral ACL-transection (ACLT). Micro-computed tomography was used
      to scan the three-dimensional (3D) bone architecture of the proximal tibia, and
      analysis was performed on the subchondral plate and cancellous bone in the
      epiphyseal and metaphyseal regions of each bone. RESULTS: A decrease in
      cancellous bone mass (BV/TV) and subchondral plate thickness (Ct.Th) was observed
      16 week post-ACLT, and the trend was statistically significant for the long-term
      animals (>5 year post-ACLT: BV/TV decreased 16.8%, P<0.003; Ct.Th decreased
      36.8%, P<0.03). A decrease in bone mass was also observed as a function of animal
      age by comparing the young and aged normal control animals, however ACLT
      intensified those changes, particularly Ct.Th (P<0.009) and anisotropy (P<0.045).
      It was speculated that decreased internal joint loading despite normal kinematics
      may play an important role in the long-term reduction of cancellous bone volume
      and subchondral plate thinning. CONCLUSIONS: The periarticular bone changes
      measured in this study were concurrent with articular cartilage degeneration, and
      suggest that bone may be a contributing factor in the aetiology of post-traumatic
      OA development.

PMID- 15727891
TI  - Immature murine articular chondrocytes in primary culture: a new tool for
      investigating cartilage.
AB  - OBJECTIVE: Many genetically modified animal models are providing new keys for
      unlocking the pathophysiology of cartilage degradation. To produce a tool for
      cellular and molecular studies in genetically engineered murine models, we
      defined the optimal culture conditions for primary cultures of articular
      chondrocytes from newborn mice (C57Bl/6). METHODS: To determine whether the
      cultured cells exhibited the typical articular chondrocyte phenotype, we examined
      several morphological, biochemical, and functional features. RESULTS: The cells
      had the typical chondrocyte morphology, with a rounded or polygonal shape.
      Immunolocalization studies showed high levels of type II collagen and aggrecan
      expression, together with sulfated glycosaminoglycan accumulation. Type II
      collagen and aggrecan expression decreased with passaging. In contrast, type I
      collagen expression was low in primary cultures and high after four passages,
      indicating a fibroblast phenotype. To evaluate the functional integrity of our
      cultured cells, we evaluated their ability to produce prostaglandin E2 (PGE2) and
      nitric oxide (NO) in response to the catabolic cytokine interleukin (IL)-1beta
      (10 ng/ml). Production of both PGE2 and NO increased significantly as compared to
      untreated controls. In addition, IL-1beta induced COX-2 expression by the
      cultured cells, as shown by Western blotting. CONCLUSIONS: Since functional and
      molecular parameters can be measured readily in mice, the immature murine
      articular chondrocyte (iMAC) model described here should prove a powerful tool
      for research, particularly as many transgenic and knockout mouse strains are
      available, even if iMACs are not optimal substitutes for human chondrocytes.

PMID- 15727892
TI  - Inhibition of adenosine kinase attenuates interleukin-1- and lipopolysaccharide
      induced alterations in articular cartilage metabolism.
AB  - OBJECTIVE: To investigate the effect of adenosine kinase inhibition on
      interleukin (IL)-1beta- and lipopolysaccharide (LPS)-induced cartilage damage.
      DESIGN: Articular cartilage was obtained from the metacarpophalangeal joints of
      10 young adult horses. Following a stabilization period, weighed cartilage
      explants were exposed to IL-1beta (10 ng/ml) or LPS (50 microg/ml) to induce
      cartilage degradation. To test the potential protective effects of adenosine,
      these explants were simultaneously exposed to adenosine (100 microM), the
      adenosine kinase inhibitor 5'iodotubercidin (ITU, 1 microM) or to both adenosine
      and ITU. After 72 h in culture, conditioned medium was collected for evaluation
      of glycosaminoglycan (GAG), nitric oxide (NO), prostaglandin E2 (PGE2) and matrix
      metalloproteinase (MMP)-3 release. RESULTS: IL-1beta and LPS stimulated
      significant release of GAG, NO, PGE2 and MMP-3. Incubation with ITU significantly
      inhibited both IL-1beta- and LPS-induced GAG release, but did not alter MMP-3
      production. Exposure to ITU also reduced IL-1beta-induced PGE2 release and LPS
      induced NO production. Direct adenosine supplementation did not attenuate the
      effects of IL-1beta or LPS, and the addition of adenosine or ITU in the absence
      of IL-1beta or LPS did not have any detectable effect on cartilage metabolism in
      this model. CONCLUSIONS: The adenosine kinase inhibitor ITU attenuated
      experimentally induced cartilage damage in an in vitro cartilage explant model.
      Release of adenosine from chondrocytes may play a role in the cellular response
      to tissue damage in arthritic conditions and modulation of these pathways in the
      joint may have potential for treatment of arthropathies.

PMID- 15727894
TI  - Identification of an immunogenic candidate for the elicitation of severe acute
      inflammatory reactions (SAIRs) to hylan G-F 20.

PMID- 15727893
TI  - New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative
      related type II collagen network degradation in patients with osteoarthritis and
      rheumatoid arthritis.
AB  - OBJECTIVE: Protein nitration is a prominent feature of inflammatory processes in
      the joint. We have developed immunoassays specific for a peptide of the alpha
      helical region of type II collagen 108HRGYPGLDG116 (Coll 2-1) and its nitrated
      form 108HRGY(NO2)PGLDG116 (Coll 2-1 NO2) in biological fluids. DESIGN: Coll 2-1
      and Coll 2-1 NO2 peptides were injected into rabbits. Two antisera (D3 and D37)
      were selected for their specificity and affinity and used to develop specific
      immunoassays. Coll 2-1 and Coll 2-1 NO2 were measured in sera of 242 healthy
      subjects (N), 67 patients with primary knee osteoarthritis (OA) and 19 patients
      with rheumatoid arthritis (RA). RESULTS: In healthy subjects, Coll 2-1 and Coll 2
      1 NO2 concentrations were 125.13+/-3.71 nM and 0.16+/-0.08 nM, respectively. In
      OA and RA, Coll 2-1 and Coll 2-1 NO2 serum levels were found to be significantly
      increased compared to controls of the same range of age (Coll 2-1: OA: 200.80+/
      8.98 nM, RA: 172.30+/-19.05 nM, normal: 126.60+/-6.70 nM and Coll 2-1 NO2: OA:
      0.26+/-0.02, RA: 0.38+/-0.05, normal: 0.12+/-0.01 nM). Coll 2-1 NO2 levels were
      significantly more elevated in RA than in OA patients (P<0.05). As a consequence,
      the ratio Coll 2-1 NO2/Coll 2-1 was 1.6 times higher in RA than in OA subjects.
      No relationship was found between the radiological OA severity and the levels of
      Coll 2-1 and Coll 2-1 NO2 in serum. Coll 2-1 NO2, but not Coll 2-1, was
      correlated with C-reactive protein in the sera of OA and RA patients.
      CONCLUSIONS: The determination of both Coll 2-1 and Coll 2-1 NO2 in serum of
      arthritic patients seems to be a promising useful tool for the detection of
      oxidative-related cartilage degradation episode. Further, these markers could be
      helpful for monitoring the effects of anti-inflammatory or antioxidant drugs on
      cartilage degradation.

PMID- 15727895
TI  - Benign hereditary leukopenia-neutropenia does not result from lack of low grade
      inflammation. A new look in the era of microinflammation.
AB  - The purpose of this study was to determine whether benign hereditary leukopenia
      neutropenia in Yemenites may be reflective of an absent or a lesser degree of
      chronic low grade inflammation that has been documented to exist in most
      apparently healthy subjects. The white blood cell count (WBCC), fibrinogen as
      well as high sensitivity C-reactive protein (hs-CRP) concentrations were
      determined in a group of apparently healthy individuals during their routine
      health screening program. These inflammatory biomarkers in a group of 82 Yemenite
      Jews were compared to those measured in a group of 1817 individuals whose parents
      immigrated to Israel from Central and East Europe, from countries surrounding the
      Mediterranean Sea as well as the Middle East. The two study groups were matched
      for possible confounding factors that may have an influence on the intensity of
      the microinflammatory response including age, gender, body mass index, components
      of the metabolic syndrome and the Ten Year Calculated Coronary Heart Disease
      Framingham Risk Score. The expected reduced WBCC was noted in the group of
      Yemenite Jews (6.99 +/- 1.64 versus 5.88 +/- 2.06 x 10(3)/microL cells, P =
      0.001). However, they had significantly enhanced concentrations of hs-CRP, the
      respective values being 2.1 +/- 2 versus 1.4 +/- 2.4 mg/L in men (P = 0.002) and
      2.5 +/- 2.2 versus 1.4 +/- 2.9 in women (P < 0.0005). An increased concentration
      of fibrinogen was found in the Yemenite Jews, although the difference was not
      statistically significant in men. Thus, the leukopenia-neutropenia in Yemenite
      Jews is probably not an expression of an absent or lesser degree of chronic low
      grade inflammation. These findings shed more light on the potential mechanisms
      that are responsible for the low WBCC in this particular ethnic group.

PMID- 15727896
TI  - Reinfusion of aspirated pericardial blood during CPB. Part I. Hypothesis:
      laparotomy sponges are a significant part of the CPB circuit?
AB  - Blood accumulating in the pericardial sac is routinely reinfused during
      cardiopulmonary bypass (CPB) surgery. Such reinfusion has been associated with an
      increased incidence of serious complications such as coagulopathy, systemic
      inflammation, and neurologic sequelae. We hypothesize that some of these
      complications occur because the reinfused blood has been exposed to and activated
      by laparotomy sponges used to elevate the heart during vein graft emplacement.
      Such laparotomy sponges expose accumulating pericardial blood to a large, raw,
      cotton surface with an area approximately five times that of the CPB circuit
      (excluding the biocompatible oxygenator membrane). Because the reinfused blood
      has been exposed to this surface, the sponge becomes, in essence, a significant
      though inapparent-part of the CPB circuit. Steps should be taken to either
      eliminate the sponge or to reduce the area of this foreign surface and make it
      more biocompatible.

PMID- 15727897
TI  - Reinfusion of aspirated pericardial blood during CPB. Part II. Laparotomy sponges
      are hazardous parts of the CPB circuit?
AB  - Usually, cotton laparotomy sponges are discarded when they become blood soaked.
      During bypass surgery, however, they are often wrung out into the pericardial sac
      and the contents of the sac are aspirated into the cardiopulmonary bypass (CPB)
      circuit. After cardiopulmonary bypass, many patients give evidence of mental
      confusion, excessive bleeding, and systemic inflammatory response syndrome
      (SIRS). We believe that a possible cause is reinfusion of blood that has been
      activated by contact with laparotomy sponges and contains fibrin microemboli and
      thrombin. Thrombin production, soluble fibrin (SF) development, and fibrinogen
      disappearance were measured, over time, in model systems composed of increasing
      amounts (0-10-20 microL) of tissue factor (TF) in 4 ml of anticoagulated blood
      distributed through the interstices of a 49-cm(2) laparotomy sponge. Clotting
      occurred in all of the sponges. Clotting was accelerated by the presence of TF.
      Without TF, clotting occurred in an average of 28 min (range 17-39). With 10 and
      20 microl TF, clotting occurred in 20 (range 11-27) and 13 (range 10-16) min,
      respectively. Thrombin at a level of approximately 16 NIHU/ml whole blood was
      present in several donors for 10-20 min after clotting was complete. If 120 ml of
      blood was to be wrung from a full-sized laparotomy sponge at this point in time,
      it could contain as much as 2000 units of thrombin.

PMID- 15727898
TI  - Intestinal over-expression of iron transporters induces iron overload in birds in
      captivity.
AB  - Hereditary hemochromatosis (HH) is a frequent genetic disease of older subjects
      of northern European descent. It is characterized by increased iron absorption
      and severe iron overloading in parenchymal organs. A similar disturbance of iron
      metabolism occurs in specific animal species in captivity. To address the key
      features leading to high absorption and thus to iron overload in these animals,
      we have studied the two iron transport proteins DMT1 and Ireg1 in the best-known
      susceptible species, the mynah bird. Here, we show that these birds have a high
      expression of DMT1 in the duodenum and also a strikingly high expression of Ireg1
      along the whole small intestine. We believe that the iron accumulation in
      susceptible species only occurs in captivity because of a genotypic adaptation to
      their natural environment, where contrary to captivity, dietary iron is hardly
      available. The Caucasian population carrying mutations leading to iron overload
      today may have also benefited from the genetic advantage of up-regulating iron
      transport millennia ago, when dietary iron was scarce.

PMID- 15727899
TI  - Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin
      mutation and unique clinical features.
AB  - Hereditary hemochromatosis is a common disorder of iron metabolism most
      frequently associated with mutations in the HFE gene. Hereditary hemochromatosis
      may be caused by other less common genetic mutations including those in the
      ferroportin gene. Whereas hereditary hemochromatosis associated with HFE
      mutations is an autosomal recessive disorder, essentially all cases of hereditary
      hemochromatosis associated with ferroportin mutations follow an autosomal
      dominant pattern of inheritance, and most cases are notable for the lack of an
      elevated transferrin saturation and presence of iron deposition in Kupffer cells.
      This report describes the clinical and laboratory features of a family with
      hereditary hemochromatosis associated with a previously unrecognized ferroportin
      mutation (Cys326Ser). Three generations of the family are described. The disease
      in this family is notable for young age at onset, elevated transferrin saturation
      values, and hepatocyte iron deposition. The distinct molecular and clinical
      features reflect the heterogeneous nature of this disease.

PMID- 15727900
TI  - Intra-leukocytic hemosiderin inclusions detected as pseudoeosinophils by
      automated depolarization analysis in a patient with beta-thalassaemia major and
      immune hemolysis.
AB  - This report describes a patient with intra-leukocytic hemosiderin inclusions
      associated with iron overload and acute infection. These inclusions resulted in a
      false identification of eosinophils rather than neutrophils using an automated
      analyzer. The analyzer interpreted the aberrant increased depolarization as a
      reflection of eosinophils. No eosinophils were found by examination of the blood
      smear. The implications for the hematology morphologist is that visual inspection
      of a blood smear is nearly always indicated whenever any departure from strict
      normality is noted in the output from an automated blood cell counter.

PMID- 15727901
TI  - Hb Montfermeil [beta 130(H8) Tyr-->Cys]: suggests a key role for the interaction
      between helix A and H in oxygen affinity of the hemoglobin molecule.
AB  - Hb Montfermeil [beta130(H8) Tyr-->Cys] is a high oxygen affinity variant causing
      erythrocytosis. The cysteine replacement is buried in the inside of the beta
      chain where it alters the interactions between helix A and H, with a further
      effect on helix E. This position has already been proposed to contribute to the
      difference in oxygen affinity between human and bovine hemoglobins. Three
      dimensional structural considerations and comparison of the functional behavior
      of other variants suggest that this region is an important determinant of the
      intrinsic oxygen affinity of the hemoglobin molecule.

PMID- 15727902
TI  - Spontaneous switch from Agamma- to beta-globin promoter activity in a stable
      transfected dual reporter vector.
AB  - Here it is analyzed the expression of a mini locus dual reporter construct
      composed by a micro-LCR and by the promoters for (A)gamma- and beta-globin gene,
      each one linked to a different Luciferase, in stably transfected GM979 cells for
      as long as 1-2 years from transfection. The transfected GM979 cells rapidly
      (within 1 month) evolved into a stable population which expresses constant levels
      of reporters for more than a year of continuous bulk culture. No silencing of the
      inserted construct was observed over time. In contrast, after 1 month, the
      reporter activity (both from (A)gamma- and beta-promoter) expressed per cell
      increased over time. The analysis of the Luciferase contained in single cell
      clones indicated that the higher reporter activity was due to increased gene
      expression per cell rather than to clonal selection of the most expressing
      clones. Since the activity driven by the beta-promoter increased 10-fold more
      than that driven by the (A)gamma one, the ratio between (A)gamma-driven/((A)gamma
      driven + beta-driven) reporter activity in the cells decreased after 1 month and
      became similar to the gamma/(gamma + beta) globin mRNA ratio expressed by adult
      erythroid cells. Moreover, although both cells from early and late bulk culture
      responded to incubation with butyric acid, a known inducer of fetal globin gene
      expression, by increasing the reporter activity driven by the (A)gamma-promoter,
      only cells from late bulk culture decreased, as normal primary erythroblasts do,
      the activity of the reporter driven by the beta-promoter. These results suggest
      that the rapid changes in activity driven by the (A)gamma- and beta-globin
      promoters occurring during the first month after transfection may represent a
      novel in vitro model to study epigenetic regulation of the (A)gamma- and beta
      promoter during the fetal to adult hemoglobin switch and confirm GM979 cells
      stably transfected with the dual reporter construct as a reliable assay for
      automated screening of chemical inducers of fetal globin gene activation.

PMID- 15727904
TI  - Pyruvate kinase regulatory element 1 (PKR-RE1) mediates hexokinase gene
      expression in K562 cells.
AB  - We have established the functional importance of PKR-RE1, a necessary
      transcriptional regulatory element in the erythroid-specific promoter of the
      human pyruvate kinase gene (PKLR). Here, we demonstrate by electrophoretic
      mobility shift assay (EMSA) that the DNA-protein interaction at PKR-RE1 involves
      a CTGTC motif. Because the same motif is also present in the erythroid-specific
      promoter of the hexokinase gene (HK1), we confirmed its functional relevance by
      in vitro transfection in K562 cells. Moreover, EMSA demonstrated that the CTGTC
      motif in both the PKLR and HK1 promoters mediates binding of the same protein.
      Therefore, we postulate a more general role of PKR-RE1 in erythroid-specific gene
      expression.

PMID- 15727903
TI  - Imatinib mesylate radiosensitizes human glioblastoma cells through inhibition of
      platelet-derived growth factor receptor.
AB  - Imatinib mesylate is a small molecule inhibitor of the c-Abl, platelet-derived
      growth factor (PDGF) receptor and c-Kit tyrosine kinases that is approved for the
      treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) and
      gastrointestinal stromal tumors. Glioblastoma multiforme is a highly malignant
      primary brain tumor that is usually treated with surgery and/or radiotherapy.
      Previous studies implicate an autocrine loop caused by high expression of PDGF
      and its receptor, PDGFR, in the proliferation of some glioblastomas. Here, we
      demonstrate that pretreatment of a human glioblastoma cell line, RuSi RS1, with
      imatinib significantly enhanced the cytotoxic effect of ionizing radiation. This
      effect was not seen in human breast cancer (BT20) and colon cancer (WiDr) cell
      lines. Whereas c-Abl and c-Kit were expressed about equally in the three cell
      lines, RuSi RS1 cells showed significantly higher expression of PDGFR-beta
      protein in comparison to BT20 and WiDr. Imatinib treatment of RuSi RS1 cells
      decreased overall levels of cellular tyrosine phosphorylation and specifically
      inhibited phosphorylation of PDGFR-beta, while c-Abl was not prominently
      activated in these cells. These results suggest that imatinib may have clinical
      utility as a radiosensitizer in the treatment of human glioblastoma, possibly
      through disruption of an autocrine PDGF/PDGFR loop.

PMID- 15727905
TI  - Molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) variants in
      the south of Thailand and identification of a novel variant (G6PD
      Songklanagarind).
AB  - Two hundred and twenty-five G6PD-deficient subjects in Songklanagarind Hospital
      in the south of Thailand comprising 210 males and 15 females were studied.
      Neonatal jaundice was detected in 85% of these patients. Acute hemolysis related
      to infection was detected in 17.3% of the G6PD-deficient subjects. Drug-induced
      acute hemolysis was detected in 1.8% and favism was observed in 3.6% of G6PD
      deficient patients. The molecular analysis was performed on 134 G6PD-deficient
      individuals by a combination of PCR-RFLP, multiplex polymerase chain reaction by
      multiple tandem forward primers and a common reverse primer assay (MPTP) and DNA
      sequencing to characterize the mutations of the samples with abnormal MPTP bands.
      We found 10 different missense G6PD mutations and the three most common variants
      were G6PD Viangchan 871,G-->A (31.3%), G6PD Kaiping 1388,G-->A (20.1%) and G6PD
      Mahidol 487,G-->A (17.2%) followed by G6PD Canton 1376,G-->T (9.7%), G6PD Union
      1360,C-->T (2.2%), G6PD Gaohe 95,A-->G (1.5%), G6PD Quing Yuan 392,G-->T (0.7%),
      G6PD Mediterranean 563,C-->T (0.7%), G6PD Songklanagarind 196,T-->A (0.7%),
      silent mutation 1311,C-->T (6.7%), and uncharacterized variant (9%). A novel
      missense mutation at codon 196, TTC-->ATC in exon 4 of the G6PD gene predicting a
      single amino acid substitution, Phe66Ile was identified and we designated this
      novel class II variant as G6PD Songklanagarind. The G6PD variants among the Thais
      in the southern part are heterogeneous and G6PD Viangchan, Kaiping, Mahidol, and
      Canton variants account for about 78% of the cases. Our findings provide some
      evidence that G6PD Viangchan and Mahidol are common Southeast Asian variants and
      support the theory of genetic drifts throughout Southeast Asia.

PMID- 15727906
TI  - European veterinary education: what does harmonisation mean?

PMID- 15727907
TI  - Equine dentistry--"the state of the art and the state of the science".

PMID- 15727908
TI  - Foot-and-mouth disease: the vital need for collaboration as an aid to disease
      elimination.

PMID- 15727909
TI  - A review of equine dental disorders.
AB  - Equine dentistry is a very important but until recently rather neglected area of
      equine practice, with many horses suffering from undiagnosed, painful dental
      disorders. A thorough clinical examination using a full mouth speculum is a pre
      requisite to performing any equine dental procedure. Common incisor disorders
      include: prolonged retention of deciduous incisors, supernumerary incisors and
      overjet--the latter usually accompanied by cheek teeth (CT) overgrowths. Overjet
      can be surgically corrected, but perhaps should not be in breeding animals. In
      younger horses, traumatically fractured incisors with pulpar exposure may survive
      by laying down tertiary dentine. Loss or maleruption of incisors can cause uneven
      occlusal wear that can affect mastication. Idiopathic fractures and apical
      infection of incisors are rare. The main disorder of canine teeth is the
      development of calculus of the lower canines, and occasionally, developmental
      displacements and traumatic fractures. The main indications for extraction of
      "wolf teeth" (Triadan 05s) are the presence of displaced or enlarged wolf teeth,
      or their presence in the mandible. Developmental abnormalities of the CT include;
      rostral positioning of the upper CT rows in relation to the lower CT rows--with
      resultant development of focal overgrowths on the upper 06s and the lower 11s.
      Displaced CT develop overgrowths on unopposed aspects of the teeth and also
      develop periodontal disease in the inevitable abnormal spaces (diastemata) that
      are present between displaced and normal teeth. Diastemata of the CT due to
      excessive developmental spacing between the CT or to inadequate compression of
      the CT rows is a common but under diagnosed problem in many horses and causes
      very painful periodontal disease and quidding. Supernumerary CT mainly occur at
      the caudal aspect of the CT rows and periodontal disease commonly occurs around
      these teeth. Eruption disorders of CT include prolonged retention of remnants of
      deciduous CT ("caps") and vertical impaction of erupting CT that may lead to
      large eruption cysts and possibly then to apical infections. Disorders of wear,
      especially enamel overgrowths ("enamel points"), are the main equine dental
      disorder and are believed to be largely due to the dietary alterations associated
      with domestication. If untreated, such disorders will eventually lead to more
      severe CT disorders such as shearmouth and also to widespread periodontal
      disease. More focal dental overgrowths will develop opposite any CT not in full
      opposition to their counterpart, e.g., following maleruption of or loss of a CT.
      Because of the great length of reserve crown in young (hypsodont) CT, apical
      infections usually cause infection of the supporting bones and depending on the
      CT involved, cause facial swellings and fistulae and possibly sinusitis.
      Diagnosis of apical infection requires radiography, and possibly scintigraphy and
      other advanced imaging techniques in some early cases. When possible, oral
      extraction of affected CT is advocated, because it reduces the costs and risks of
      general anaesthesia and has much less post-extraction sequelae than CT repulsion
      or buccotomy.

PMID- 15727910
TI  - Congenital sensorineural deafness in dogs: a molecular genetic approach toward
      unravelling the responsible genes.
AB  - Deafness is often diagnosed in different dog breeds and has been identified as a
      significant problem for breeders, owners and clinicians. The aetiology can be
      inherited or acquired, and a distinction must be made between sensorineural and
      conductive forms of deafness. This paper provides a brief overview of the
      varieties of findings in different dog breeds and in one breed in particular
      including prevalence, phenotypic and gender associations, histology, modes of
      inheritance and the number of contributing genes in congenital sensorineural
      deafness. We have also described molecular genetic approaches to canine hearing
      loss and discuss how comparative genomics could help reduce the prevalence of
      deafness in affected breeds leading to new insights into the molecular mechanisms
      of auditory function in both dogs and humans.

PMID- 15727911
TI  - A review of foot-and-mouth disease with special consideration for the clinical
      and epidemiological factors relevant to predictive modelling of the disease.
AB  - Modelling the epidemiology of foot-and-mouth disease (FMD) has been undertaken
      since the early 1970s. We review here clinical factors and modelling procedures
      that have been used in the past, differentiating between those that have proved
      to be more relevant in controlling FMD epidemics, and those that have showed less
      significance. During the 2001 UK FMD epidemic, many previously developed FMD
      models were available for consideration and use. Accurate epidemiological models
      can become useful tools for determining relevant control policies for different
      scenarios and, conversely, inaccurate models may become an abuse for disease
      control. Inaccuracy presents two opposing difficulties. Firstly, too much control
      (in terms of animal slaughter for 2001) would negatively impact the farming
      community for many subsequent years, whilst too little control would permit an
      epidemic to persist. Accuracy however, presents the optimal permutation of
      control measures that could be implemented for a given set of conditions, and is
      a prerequisite to boosting public confidence in the use of epidemiological models
      for future epidemics.

PMID- 15727912
TI  - European veterinary education: a bridge to quality.
AB  - The aim of this review is to provide an insight into the current state of, and
      future changes in, veterinary education within the European Community, as well as
      the role of the European Association of Establishments for Veterinary Education
      (EAEVE) in evaluating and raising standards of education and training. It also
      describes the role of EAEVE in developing strategies for changes in the future.
      Veterinary schools have traditionally aimed at producing the omnicompetent
      veterinarian at graduation. Many have questioned whether this is possible, and a
      recent European Commission (EC) funded market survey has confirmed that this is
      indeed an impossible task and has identified the requirements of society within
      the European Union (EU) for veterinary services in the future. There is however a
      need to change the current 1978 European Directive. The current mechanisms which
      have been used by EAEVE to evaluate over 100 veterinary schools in Europe and
      their relationship with other systems of appraisal are described. The future of
      veterinary education within the context of higher education in Europe as part of
      the Bologna process and in relation to standards of veterinary education
      worldwide are discussed. Whilst the merits of standardisation of educational
      quality so that there can be mutual recognition of qualifications are supported,
      the need to preserve the strengths associated with the diversity of approaches
      and teaching methods is strongly advocated.

PMID- 15727913
TI  - Differential regulation of the GLUT1 and GLUT3 glucose transporters by growth
      factors and pro-inflammatory cytokines in equine articular chondrocytes.
AB  - Glucose serves as the major energy substrate for articular chondrocytes and as
      the main precursor for the synthesis of extracellular matrix glycosaminoglycans
      in cartilage. Chondrocytes have been shown to express several glucose transporter
      (GLUT) isoforms including GLUT1 and GLUT3. The aim of this investigation was to
      determine the effects of endocrine and cytokine factors on the capacity of equine
      articular chondrocytes for transporting 2-deoxy-d-[2,6-3H] glucose and on the
      expression levels of GLUT1 and GLUT3. Chondrocytes maintained in monolayer
      culture were stimulated for 24 h with TNF-alpha (100 ng mL(-1)), IL-1beta (100 ng
      mL(-1)), IGF-I (20 ng mL(-1)), TGF-beta (20 ng mL(-1)) and insulin (12.5 microg
      mL(-1)) before measuring uptake of non-metabolizable 2-deoxyglucose in the
      presence and absence of the glucose transport inhibitor cytochalasin B.
      Polyclonal antibodies to GLUT1 and GLUT were used to compare GLUT1 and GLUT3
      expression in stimulated and un-stimulated alginate encapsulated chondrocytes by
      Western blotting. Results indicated that 2-deoxyglucose uptake was inhibited by
      up to 95% in the presence of cytochalasin B suggesting that glucose uptake into
      equine chondrocytes is GLUT-mediated. Insulin had no effect on glucose uptake,
      but treatment with IGF-I, TGF-beta, IL-1beta and TNF-alpha resulted in a
      significant increase (>65%) in 2-deoxyglucose uptake compared to control values.
      GLUT1 was found to be increased in chondrocytes stimulated with all the growth
      factors and cytokines but GLUT 3 was only upregulated by IGF-I. The data
      presented support a critical role for glucose in the responses of equine
      articular chondrocytes to pro-inflammatory cytokines and anabolic endocrine
      factors.

PMID- 15727914
TI  - Reliability of cardiorespiratory measurements with a new ergospirometer during
      intense treadmill exercise in Thoroughbred horses.
AB  - This study investigated the reliability of measurements with a new equine
      ergospirometer (Quadflow). Heart rate and blood lactate responses during exercise
      in horses wearing the Quadflow and an open flow mask were also compared. The mean
      percentage error of the oxygen uptake measurements was 8.2% (range 2.1-12.5%).
      Percent error for peak expiratory flow rates ranged from 6.1% to 9.4 %, and for
      minute ventilation from 2.5% to 7.4%. The coefficients of variation of the means
      of four measurements in two horses exercising continuously at 9.0 m/s were <5%
      for variables related to pulmonary ventilation, and was 7.7% for oxygen uptake.
      The Quadflow mask resulted in small increases in blood lactate concentration and
      relative heart rate during submaximal exercise. It was concluded that between-
      and within-test reliability statistics for important measurements in equine
      clinical exercise testing were acceptable for routine use in a veterinary
      practice or research laboratory.

PMID- 15727915
TI  - Bovine digital dermatitis and severe virulent ovine foot rot: a common
      spirochaetal pathogenesis.
AB  - A potential pathological role for spirochaetes in bovine digital dermatitis
      (bovine DD) and severe virulent ovine foot rot (SVOFR) has been considered and a
      treponeme isolate obtained from each disease in the UK. In this work, we have
      investigated the hypothesis that the two diseases may have a shared (common)
      spirochaetal aetiology. Experiments were designed to identify serological
      similarities and differences between the two spirochaetes; an enzyme-linked
      immunosorbent assay (ELISA) was developed to detect anti-treponeme antibodies in
      the sera of cows and sheep against the two-treponeme isolates. Sera were further
      tested for antigen reactivity by Western blotting. Cattle and sheep with bovine
      DD and SVOFR, respectively, had increased seropositivity rates to both treponeme
      isolates, with different patterns of reactivity between farms. In some cattle
      herds, significant correlations were shown between antibodies to bovine DD
      treponemes and SVOFR treponemes (P<0.001). In other herds, there was no apparent
      cross reaction, suggesting the presence of more than one treponeme in bovine DD
      on some farms. There was no significant correlation between the two treponeme
      isolates when ELISA-tested against 58 sheep sera from SVOFR cases (P>0.05); sheep
      showed strong evidence of reactivity to one or the other treponeme antigens, but
      never to both. Western blotting against both treponeme antigens showed that they
      frequently displayed different antigen epitopes, although some minor bands were
      common to both organisms. The data suggest that there are a number of
      spirochaetes in UK farms, which could be involved in the pathogenesis of either
      bovine DD or SVOFR.

PMID- 15727916
TI  - Pattern recognition and feature extraction of canine celiac and cranial
      mesenteric arterial waveforms: normal versus chronic enteropathy--a pilot study.
AB  - In this pilot study, we hypothesize that waveform patterns of the celiac and
      cranial mesenteric arteries differ pre- and post-prandially in normal dogs
      compared to those with chronic enteropathy. We further suggest that it is
      possible to classify these findings according to the type of disease present.
      Eleven dogs with chronic enteropathy and eight normal dogs were examined. Doppler
      examinations were performed at times 0 (fasted), and at 20, 40, 60 and 90 min
      post-prandially. The waveform shapes were described and the following features
      were extracted: resistive and pulsatility index, mean maximum velocity, mean
      diastolic velocity, peak systolic velocity, early diastolic notch ratio and the
      deceleration time interval. Dogs with inflammatory bowel disease had either lower
      or absent flow at fasting in early diastole compared to the other groups.
      Resistive and pulsatility indices decreased during digestion in all groups except
      those with protein losing enteropathy. The increase in mean diastolic flow during
      digestion in affected dogs was either lacking (protein-losing enteropathy) or
      significantly lower (inflammatory bowel disease, P<0.05) compared to normal dogs.
      Dogs with chronic enteropathies had abnormal arterial waveform shapes and
      suboptimal increases in diastolic blood flow during digestion and these findings
      worsened with the severity of the histological lesions present. Doppler
      ultrasound of the celiac and mesenteric arteries has great potential to enhance
      our understanding of intestinal disease in conscious dogs.

PMID- 15727917
TI  - Blood-oxygen binding in healthy Standardbred horses.
AB  - The purpose of this study was to determine the effect of regulating factors on
      the oxygen equilibrium curve (OEC) under standard conditions and then to
      calculate the oxygen extraction between arterial and jugular venous blood in
      healthy Standardbred horses. The results were compared to those previously
      obtained in humans and cattle, using the same experimental method. The partial
      oxygen pressure at 50% saturation of haemoglobin, measured under standard
      conditions (standard P50), was 24.8+/-2.0 (SD of mean) mmHg. This value was
      similar to the cattle standard P50 (25.0+/-1.4 mmHg, SD of mean) but lower than
      the human standard P50 (26.6+/-1.2 mmHg, SD of mean) previously reported using
      the same experimental method. The effects of regulating factors on the standard
      OEC were also determined, and a major effect of pH and temperature was noted. In
      contrast, partial carbon dioxide pressure played only a minor role in horses,
      compared to cattle and humans. No significant correlation was found between
      phosphate and chloride concentrations and standard P50.

PMID- 15727918
TI  - Distribution of new methylene blue injected into the caudal epidural space in
      cattle.
AB  - To investigate the distribution of solutions injected into the first
      intercoccygeal epidural space, 24 adult, standing cattle were randomly assigned
      to 5-, 10- and 20-mL groups and injected with 0.12% new methylene blue (NMB) in
      0.9% saline. Ten heifers received 1 mL NMB solution/100 kg of body weight. There
      was a significant correlation between the injected volume and the number of
      cranially stained spinal segments in three adult cattle groups (correlation
      coefficient R2=0.46; P<0.0001). In three cattle, NMB solution did not distribute
      more than one spinal segment cranially from the injection site due either to
      fibrosis of the epidural tissue or to inadvertent intravenous administration into
      the epidural vein. The study showed that the larger the volume of solution
      injected, the greater the spread with increased individual variation. The results
      could form the basis for determining the volume of injection required and for
      evaluating the pharmacokinetics of anaesthetics used in caudal epidural
      anaesthesia.

PMID- 15727919
TI  - The role of metallothionein and zinc in hepatic copper accumulation in cattle.
AB  - The role of metallothionein (MT) and zinc (Zn) in hepatic copper (Cu)
      accumulation in calves from a region in North-West Spain has been investigated.
      In this region there is intensive pig farming, and animals with liver Cu
      concentrations above normal are not uncommon. Concentrations of hepatic MT were
      not related to Cu accumulation but were strongly dependent on the Zn status of
      the animal. When analysing the metal content bound to MT it was observed that Cu
      MT values, in the same way as Zn-MT, were directly correlated with MT
      concentrations in the liver, indicating that although Cu is a poor inducer of MT
      synthesis, it can compete with Zn for MT binding sites. The ability of Cu to
      displace Zn from MT is highly dependent on the Cu:Zn ratio in the cell, Cu being
      the main metal in MT at the higher levels of Cu exposure in Galician cattle. In
      spite of this, the percentage of the total hepatic Cu bound to MT is very low in
      these animals, indicating that cattle have a very limited capacity to accumulate
      Cu-MT in the liver, and may therefore have a greater susceptibility to Cu
      toxicosis.

PMID- 15727921
TI  - Topical fusidic acid/betamethasone-containing gel compared to systemic therapy in
      the treatment of canine acute moist dermatitis.
AB  - The efficacy of a topical preparation containing 0.5% fusidic acid and 0.1%
      betamethasone-17-valerate was compared to a systemic therapy (comprising a
      combination of parenteral dexamethasone and oral clavulanate-potentiated
      amoxycillin) in the treatment of 104 dogs with acute moist dermatitis.
      Significant improvement was evident after seven days in both treatment groups in
      all clinical parameters assessed and there was no significant difference in the
      overall response between the two treatment groups. Staphylococcus intermedius was
      the most frequently isolated organism from swabs at the first visit (Day 0). No
      resistance to fusidic acid or clavulanate-potentiated amoxycillin was
      encountered. The study demonstrates no difference in the clinical improvement
      achieved in canine acute moist dermatitis following topical or systemic therapy
      and that both treatment regimes represent effective treatment options for the
      condition.

PMID- 15727920
TI  - Evaluation of PCR systems for the identification and differentiation of
      Mycoplasma agalactiae and Mycoplasma bovis: a collaborative trial.
AB  - Diagnostic differentiation between the ruminant pathogens Mycoplasma agalactiae
      and Mycoplasma bovis is known to be problematic when only conventional
      serological and biochemical tests are used. The main reason for this is that both
      agents share a considerable number of related proteins and common epitopes. DNA
      based detection methods offer advantages in terms of specificity and sensitivity.
      However, there is an urgent need to compare currently used PCR assays because
      they target different genomic regions and, therefore, may perform differently. In
      the present work, five laboratories, which use PCR routinely, evaluated the
      specificity of four different PCR systems for M. agalactiae and three systems for
      M. bovis on a total of 41 strains of the two Mycoplasma species including six
      previously unidentified strains. As the vast majority of PCR examinations (97.1%
      of all tests) correctly identified the strains the specificity of all seven
      detection systems appears to be high. In four cases, incorrect identification by
      conventional diagnostic methods was rectified by PCR. Isolates from non-typical
      hosts, i.e. three M. bovis strains from small ruminants and two M. agalactiae
      strains from cattle, were characterised by sequencing the 16S and part of the 23S
      ribosomal RNA genes.

PMID- 15727922
TI  - Measurements of C-reactive protein in serum and lactate dehydrogenase in serum
      and synovial fluid of patients with osteoarthritis.
AB  - Diagnosis of osteoarthritis (OA) is based upon the clinical orthopaedic
      examination and the radiographic assessment, both of which can be non-specific
      and insensitive in early joint disease. The aim of our study was to investigate
      if there is an increase in serum levels of C-reactive protein (CRP) in
      degenerative joint disease (DJD) and if CRP could be used to help diagnose OA. We
      also wished to investigate whether it was possible to distinguish a joint with
      clinically and radiographically confirmed OA from a healthy joint by comparing
      lactate dehydrogenase (LDH) levels within the synovial fluid and the serum. We
      have shown a difference in synovial LDH levels between diseased and healthy
      joints (P<0.0001). There was also a significant difference between LDH in
      arthritic synovial fluid and serum, with no correlation between the values.
      Despite the fact that the values of our clinical patients tended to be higher
      than the values of our control group (P=0.05) all measured values were within the
      normal limits of previous publications. From these data, we conclude that single
      measurements of serum CRP do not permit detection of OA in clinical patients and
      that serum LDH is not a reliable marker for osteoarthritis. LDH levels in the
      synovial fluid could be of diagnostic value for identifying osteoarthritis.

PMID- 15727923
TI  - Oxidative status during late pregnancy and early lactation in dairy cows.
AB  - In the last few years, the detection of free radical damage and the body's
      defences against it have become increasingly important in clinical medicine as a
      complementary tool in the evaluation of metabolic status. The aim of this study
      was to evaluate, under field conditions, the anti-oxidant status of healthy cows
      during late pregnancy and lactation onset using two parameters: (1) plasma levels
      of malondialdehyde (MDA), a degradation product of lipid peroxidation, and (2)
      total antioxidant status (TAS). Results were compared with those obtained in
      another group of cows with lesser metabolic demands. We also investigated
      possible relationships between antioxidant status markers and other relevant
      blood parameters. Our results confirmed the characteristic metabolic changes
      associated with late pregnancy and early lactation. MDA and TAS provided an
      accurate reflection of the internal physiological status of the animal. The data
      indicated increased lipid peroxidation around parturition, but with wide
      individual variations that may be attributable not only to the physiological
      stage but also to unknown factors that will have to be further considered in
      future studies.

PMID- 15727924
TI  - Immunocompetence of fattening pigs fed organic versus conventional diets in
      organic versus conventional housing.
AB  - The effect of organic or conventional feeding on the immune response of pigs was
      determined using organic or conventional housing in a pig fattening unit. The
      experimental design involved four pens of four animals per housing and diet
      combination (organic housing and organic nutrition; organic housing and
      conventional nutrition; conventional housing and organic nutrition and
      conventional housing and conventional nutrition). The IgM, IgA and IgG responses
      against intramuscularly injected bovine thyroglobulin were determined as
      indicators of the antigen-specific immune responsiveness. Some general health and
      welfare related parameters were evaluated by measuring haptoglobin concentrations
      at selected times; blood lactate concentration was measured at slaughter.
      Conventional housing led to a higher IgG response three weeks after the first
      immunisation. Organic housing led to lower haptoglobin and lactate concentrations
      at slaughter, indicating a higher stress resistance in these pigs. No major
      differences between the two feeding types were found. We conclude that the immune
      responses following either a conventional or an organic diet are comparable,
      whereas organic housing can increase stress resistance at slaughter compared to
      conventional housing.

PMID- 15727925
TI  - Escherichia coli O4:NM associated with an outbreak of calf diarrhoea.

PMID- 15727927
TI  - Dermotoxic activity of a collagenolytic cell wall component from Fusobacterium
      necrophorum subsp. necrophorum.

PMID- 15727926
TI  - Flow cytometric evaluation of bound IgG on erythrocytes of anaemic dogs.
AB  - The detection of red blood cell (RBC)-bound immunoglobulins in case of anaemia
      with the direct agglutination test (DAT or Coombs test) has been reported to be
      of low sensitivity. We therefore tested the applicability of flow cytometry for
      the detection of canine IgG on RBC using two different IgG-specific secondary
      reagents: goat-anti-dog IgG (GalphaD-IgG) and rabbit-anti-dog IgG (RalphaD-IgG).
      Membrane staining RBC samples were performed at 4 degrees C. Comparisons of
      agglutination test at 37 degrees C and 4 degrees C showed, that binding of the
      secondary antibodies at 4 degrees C was more sensitive compared to agglutination
      at 37 degrees C and the two antisera differed considerable in their agglutination
      activity. Binding of GalphaD-IgG and RalphaD-IgG to RBC of healthy dogs (n=15)
      was low and mean fluorescence intensities were taken to calculate thresholds
      above which RBC of patients were judged positive. As in agglutination tests, both
      secondary antisera displayed considerable differences (concentration-dependent
      binding and histogram profiles) after flow cytometric analysis. Using flow
      cytometry, with GalphaD-IgG 8 of 17 agglutination-negative patients were positive
      and RalphaD-IgG was positive with 3 of 3 agglutination-negative RBC samples.
      Thus, flow cytometric analysis of proved to be a sensitive technique, detecting
      RBC-bound canine IgG of DAT-negative patients. The results of both techniques,
      however, are significantly influenced by the used IgG-specific polyclonal
      reagents.

PMID- 15727928
TI  - Endoscopic determination of exercise-induced pulmonary haemorrhage in Chilean
      Criollo horses.

PMID- 15727930
TI  - Formation and intracellular trafficking of lipoplexes and polyplexes.
AB  - Cationic lipid/DNA lipoplexes and cationic polymer/DNA polyplexes represent an
      attractive alternative to viral vectors for cell transfection in vitro and in
      vivo but still suffer from a relatively low efficiency. Optimization of their
      transfection efficiency may be attempted by using a trial and error approach
      consisting of synthesizing and testing a large number of derivatives. On the
      other hand, rational design of highly efficient cationic lipids and polymers
      requires a deeper understanding of the interactions between the vector and the
      DNA as well as the cellular pathways and mechanisms involved in DNA entry into
      the cell and ultimately the nucleus. In the present review, the pathways and
      mechanisms involved in lipoplex- and polyplex-mediated transfection are
      comparatively addressed and unresolved questions are highlighted.

PMID- 15727931
TI  - A novel knock-in prostate cancer model demonstrates biology similar to that of
      human prostate cancer and suitable for preclinical studies.
AB  - Preclinical studies of prostate cancer (CaP) have employed a genetically
      engineered mouse model, since there is no naturally occurring CaP in rodents. We
      have previously reported a new knock-in mouse adenocarcinoma prostate (KIMAP)
      model. In this study, we demonstrate that the new model possesses a tumor
      architecture of heterogeneity and multifocality similar to that of human CaP, by
      utilizing a new compound scoring system to compare with the PSP94 (approved gene
      symbol Msmb) gene-directed transgenic mouse CaP model (TGMAP). KIMAP mice showed
      a balanced distribution of tumor extent, which penetrated the prostate gland.
      Comparative studies on cDNA microarrays demonstrated that KIMAP tumors were
      upregulated with higher contents of immunoresponse genes, whereas PSP-TGMAP
      tumors had neuroendocrine (NE) differentiation. The majority of KIMAP mice did
      not progress to NE CaP, which was observed only at a very late stage and a low
      frequency. Several tumor marker genes characteristic of human CaP were uniquely
      identified in KIMAP tumors, including hepsin, maspin, Nkx3.1, CD10 and PSP94
      (similar to PSA), etc. The differences between these two CaP models are
      attributed to the introduction of a single endogenous knock-in mutation. Due to
      the similarities between human CaP tumors and the PSP-KIMAP tumors, this
      preclinical model may supplement the current transgenic models to study CaP more
      accurately.

PMID- 15727932
TI  - Establishing a murine pancreatic cancer CaSm model: up-regulation of CaSm is
      required for the transformed phenotype of murine pancreatic adenocarcinoma.
AB  - We have recently shown that the cancer-associated Sm-like protein (CaSm) is
      overexpressed in human pancreatic adenocarcinoma (PC). However, the role of CaSm
      in the process of neoplastic transformation remains unclear. To define further
      the role of CaSm in PC transformation, we have established a murine model based
      on the murine pancreatic cancer cell lines Panc02 and Panc03. CaSm is
      overexpressed in the aggressive Panc02 cells and expressed at much lower levels
      in the more indolent Panc03 cells. Up-regulation of CaSm in Panc03 cells
      increased in vitro proliferation and anchorage-independent growth and promoted
      subcutaneous tumor establishment and growth in syngeneic mice. Conversely,
      adenoviral down-regulation of CaSm in Panc02 led to significant inhibition of
      cellular proliferation and anchorage-independent growth in vitro and complete
      abolition of tumor growth and metastasis in vivo. Up-regulation of CaSm in NIH3T3
      resulted in loss of contact inhibition and increased soft agar colony formation
      in vitro. The requirement for CaSm overexpression for neoplastic transformation
      confirms the concept that CaSm is a critical oncogene and potential target for
      molecular intervention. Furthermore, establishment of the murine clinically
      relevant model of pancreatic metastases provides a framework for the generation
      of preclinical data to support the development of novel molecular therapies
      targeting CaSm.

PMID- 15727933
TI  - Long-term in vivo inhibition of CNS neurodegeneration by Bcl-XL gene transfer.
AB  - The inherently low regenerative capacity of the CNS demands effective strategies
      to inhibit neurodegeneration in acute lesions but also in slowly progressive
      neurological disorders. Therefore, therapeutic targets that can interact with the
      degeneration cascade to block, not just postpone, neuronal degeneration need to
      be defined. Bcl-X(L), a protein protecting the integrity of the mitochondrial
      membrane potential, was investigated for its neuroprotective properties in a long
      term in vivo model of neuronal cell death. An AAV-2-based vector was used to
      express both Bcl-X(L) and EGFP in retinal ganglion cells (RGCs) of the adult rat
      retina. Transection of the optic nerve results in degeneration of RGCs in control
      retinae, while Bcl-X(L)-overexpressing ganglion cells were protected from
      degeneration. At 2 weeks after axotomy, 94% of the transduced RGCs survived the
      lesion (15% in controls). For the first time, we investigated RGC survival up to
      8 weeks after axotomy and detected that 46% of the Bcl-X(L)-overexpressing RGCs
      still survived, representing significantly increased neuroprotection compared to
      neurotrophin-based approaches. We could also show that the axons of AAV-Bcl-X(L)
      transduced RGCs remained morphologically intact after the lesion, thus providing
      the basis for regeneration-inducing attempts.

PMID- 15727934
TI  - The lymphocytic choriomeningitis virus envelope glycoprotein targets lentiviral
      gene transfer vector to neural progenitors in the murine brain.
AB  - Feline immunodeficiency virus (FIV)-based lentiviral vectors can be targeted to
      restricted cell types by pseudotyping with envelopes from other viruses. An FIV
      vector expressing bacterial beta-galactosidase (beta-gal) and pseudotyped with
      lymphocytic choriomeningitis virus (LCMV) envelope glycoprotein was injected into
      postnatal mouse brain striatum to determine neural cell-type transduction. After
      3 or 7.5 weeks, the beta-gal-expressing cells included astrocytes in the striatum
      and in the subventricular zone (SVZ), neuroblasts along the rostral migratory
      stream, and neurons in the olfactory bulb. This pattern was suggestive of
      transduction of neural stem cells/progenitors that reside in the SVZ and
      continually generate olfactory bulb neurons. To test for transduction of SVZ type
      B astrocyte/stem cells, LCMV-pseudotyped FIV encoding Cre recombinase driven by
      an astrocyte-specific promoter was injected into the striatum of ROSA26 Cre
      reporter mice. beta-Gal expression in these mice depends on Cre recombinase
      mediated DNA recombination. beta-Gal-expressing neuroblasts and neurons were
      detected in the rostral migratory stream and olfactory bulb, respectively,
      indicating that these cells derived from an astrocytic-type stem cell. Thus, LCMV
      (WE54)-pseudotyped FIV provides a novel vector for transducing neural stem
      cells/progenitors in vivo and may prove valuable as a gene transfer vector for
      therapy of neurodegenerative diseases.

PMID- 15727935
TI  - Lentivirus-mediated gene transfer induces long-term transgene expression of BMP-2
      in vitro and new bone formation in vivo.
AB  - We examined the potential of ex vivo gene therapy to enhance bone repair using
      lentiviral vectors encoding either enhanced green fluorescent protein (EGFP) as a
      reporter gene or bone morphogenetic protein-2 (BMP-2) downstream of either the
      cytomegalovirus immediate early (CMV) promoter or the murine leukemia virus long
      terminal repeat (RhMLV) promoter derived from a murine retrovirus adapted to
      replicate in a rhesus macaque. In vitro, rat bone marrow stromal cells (BMSCs)
      transduced with Lenti-CMV-EGFP or Lenti-RhMLV-EGFP demonstrated over 90%
      transduction efficiency at 1 week and continued to demonstrate stable expression
      for 8 weeks. ELISA results demonstrated that lentivirus-mediated gene transfer
      into BMSCs induced stable BMP-2 production in vitro for 8 weeks. Increased EGFP
      and BMP-2 production was noted with the RhMLV promoter. In addition, we implanted
      BMSCs transduced with Lenti-RhMLV-BMP-2 into a muscle pouch in the hind limbs of
      severe combined immune deficient mice. Robust bone formation was noted in animals
      that received Lenti-RhMLV-BMP-2 cells at 3 weeks. These results demonstrate that
      lentiviral vectors expressing BMP-2 can induce long-term gene expression in vitro
      and new bone formation in vivo under the control of the RhMLV promoter. Prolonged
      gene expression may be advantageous when developing tissue engineering strategies
      to repair large bone defects.

PMID- 15727936
TI  - In vivo correction of murine hereditary tyrosinemia type I by phiC31 integrase
      mediated gene delivery.
AB  - Phage phiC31 integrase is a site-specific recombinase that mediates efficient
      integration of circular extrachromosomal DNA into the host genome. Here, the
      integrase system was used to transfer the fumarylacetoacetate hydrolase (FAH)
      gene into the liver of mice affected with hereditary tyrosinemia type 1.
      Approximately 3.6% of transfected hepatocytes experienced an integration event.
      The absolute frequency of integration was 1/1374. A higher proportion of
      integrase-transfected FAH+ hepatocytes displayed abnormal morphology (bizarre
      nuclei, enlarged cells) on day 25 after gene transfer, compared to cells not
      receiving integrase. The increased frequency of these abnormal cells correlated
      with the amount of integrase plasmid administered, suggesting some form of
      integrase toxicity in Fah-/- livers. The abnormal hepatocyte appearance was
      transient and livers analyzed after longer selection (90 days) showed 60%
      repopulation with only normal healthy FAH+ hepatocytes. A total of seven
      different integration sites (accounting for >90% of integration) were identified.
      Serial transplantation of integrase-corrected hepatocytes to Fah-/- recipients
      was successful, suggesting long-term viability of corrected cells and persistent
      gene expression through many rounds of cell division. The stability of transgene
      expression, relatively high integration frequency, and significant site
      specificity that characterize the phiC31 integration system suggest that it may
      have utility in many gene therapy settings.

PMID- 15727937
TI  - Thiocholesterol-based lipids for ordered assembly of bioresponsive gene carriers.
AB  - A series of thiocholesterol-based cationic lipids (TCL) has been designed and
      synthesized by the attachment of thiocholesterol to a cationic amine via a
      disulfide bond. TCL can be incorporated into liposomes and used to package DNA
      into a lipoplex, thereby protecting it from DNase digestion. DNA is rapidly
      released from the complex in the presence of low concentrations of reducing
      agents. The lipoplex mediated efficient transfection activity and had low
      cytotoxicity. To improve the biocompatibility of the cationic lipoplex, TCL were
      used as a component in the assembly of a nanolipoparticle (NLP). The particle
      surface was subsequently modified by disulfide exchange to replace the cationic
      group with a negatively charged (glutathione) or zwitterionic (cysteine) reducing
      agent. A cell-binding ligand (TAT peptide, sequence GRKKRRQRRRGYG) was then
      incorporated onto the particle surface to enhance the particle-cell recognition.
      The sequentially assembled cell-binding NLP with a zwitterionic surface gave a
      larger transfection yield than the cationic NLP at all concentrations tested. At
      low DNA concentrations, the enhancement was 80-fold. The disulfide cationic
      lipids and the sequential assembly strategy enable one to tailor the surface
      charge, hydrophilicity, and recognition elements of a nanosized gene carrier.
      This results in increased gene transfer activity in a biocompatible particle.

PMID- 15727938
TI  - Toward synthetic viruses: endosomal pH-triggered deshielding of targeted
      polyplexes greatly enhances gene transfer in vitro and in vivo.
AB  - Nonviral vectors should undergo "virus-like" changes compatible with the steps of
      gene delivery. Poly(ethylene) glycol (PEG) shielding of DNA/polycation polyplexes
      protects from nonspecific interactions with the extracellular environment. pH
      triggered removal of the shield within the endosome may be advantageous.
      Polycation and PEG were linked via acylhydrazides or pyridylhydrazines. The
      pyridylhydrazone prepared from polylysine and propionaldehyde-PEG showed the
      greatest acid-dependent hydrolysis; at pH 5, 37 degrees C for 10 min, 90%
      hydrolyzed, while at pH 7.4 the half-life was 1.5 h. Particle size and zeta
      potential measurements of the polyplexes showed complete deshielding within 1 h
      at pH 5, while at pH 7.4 the shield remained at 4 h, 37 degrees C. For gene
      transfection a targeting conjugate was also included in the polyplex, transferrin
      as ligand for K562 and Neuro2A cells and epidermal growth factor for HUH-7 and
      Renca-EGFR cells. Marker gene expression showed that the reversibly shielded
      polyplexes exhibited up to 2 log orders of magnitude higher gene expression in
      vitro and 1 log magnitude higher gene expression in an in vivo mouse model,
      compared to the stably shielded control polyplexes. Engineering of polyplexes
      with more dynamic domains is an encouraging new direction in nonviral vector
      design.

PMID- 15727939
TI  - Structure/property studies of polymeric gene delivery using a library of
      poly(beta-amino esters).
AB  - Here we describe the synthesis and characterization of a library of 486 second
      generation poly(beta-amino esters). To understand better the structure/property
      relationships governing polymeric gene delivery, we synthesized polymers with 70
      different primary structures, at 6 to 12 different molecular weights, using
      monomers previously identified as common to effective gene delivery polymers.
      This library was characterized by (1) molecular weight, (2) particle size upon
      complexation with DNA, (3) surface charge upon complexation with DNA, (4) optimal
      polymer/DNA ratio, and (5) transfection efficiency. In this library, polymers
      with 20 of the 70 primary structures possess transfection efficiencies as good as
      or better than one of the best commercially available lipid reagents,
      Lipofectamine 2000. In general, the most effective polymers condense DNA into sub
      150-nm complexes with positive surface charge. Among this group, the 2 most
      effective polymers condensed DNA to the smallest particle sizes (71 and 79 nm).
      Interestingly, the top 9 polymers were all formed from amino alcohols, and the
      structure of the 3 top performing polymers differs by only one carbon. This
      convergence in structure of the top performing polymers suggests a common mode of
      action and provides a framework with which future polymers can be designed.

PMID- 15727940
TI  - Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture
      and in vivo.
AB  - Photoproteins have played a major role in advancing our understanding of
      biological processes. A broader array of biocompatible, nontoxic, and novel
      reporters can serve to expand this potential. Here we describe the properties of
      a luciferase from the copepod marine organism Gaussia princeps. It is a monomeric
      protein composed of 185 aa (19.9 kDa) with a short coding sequence (555 bp)
      making it suitable for viral vectors. The humanized form of Gaussia luciferase
      (hGLuc) was efficiently expressed in mammalian cells following delivery by HSV-1
      amplicon vectors. It was found to be nontoxic and naturally secreted, with flash
      bioluminescence characteristics similar to those of other coelenterazine
      luciferases. hGLuc generated over 1000-fold higher bioluminescent signal
      intensity from live cells together with their immediate environment and over 100
      fold higher intensity from viable cells alone (not including secreted luciferase)
      or cell lysates, compared to humanized forms of firefly (hFLuc) and Renilla
      (hRLuc) luciferases expressed under similar conditions. Furthermore, hGLuc showed
      200-fold higher signal intensity than hRLuc and intensity comparable to that of
      hFLuc in vivo under standard imaging conditions. Gaussia luciferase provides a
      sensitive means of imaging gene delivery and other events in living cells in
      culture and in vivo, with a unique combination of features including high signal
      intensity, secretion, and ATP independence, thus being able to report from the
      cells and their environment in real time.

PMID- 15727941
TI  - Increased fluid secretion after adenoviral-mediated transfer of the human
      aquaporin-1 cDNA to irradiated miniature pig parotid glands.
AB  - The treatment of most head and neck cancer patients includes ionizing radiation
      (IR). Salivary glands in the IR field suffer irreversible damage. Previously, we
      reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1)
      cDNA to rat submandibular glands following IR restored salivary flow to near
      normal levels. It is unclear if this strategy is useful in larger animals.
      Herein, we evaluated AdhAQP1-mediated gene transfer after parotid gland IR (20
      Gy) in the miniature pig. Sixteen weeks following IR, salivation from the
      targeted gland was decreased by >80%. AdhAQP1 administration resulted in a dose
      dependent increase in parotid salivary flow to approximately 80% of pre-IR levels
      on day 3. A control Ad vector was without significant effect. The effective
      AdhAQP1 dose was 2.5 x 10(5) pfu/microl infusate, a dose that leads to comparable
      transgene expression in murine and minipig salivary glands. Three days after Ad
      vector administration little change was observed in clinical chemistry and
      hematology values. These findings demonstrate that localized delivery of AdhAQP1
      to IR-damaged salivary glands increases salivary secretion, without significant
      general adverse events, in a large animal model.

PMID- 15727942
TI  - Gene transfer to repopulating human CD34+ cells using amphotropic-, GALV-, or
      RD114-pseudotyped HIV-1-based vectors from stable producer cells.
AB  - A novel, stable human immunodeficiency virus type 1 vector packaging system,
      STAR, was tested for its ability to transduce human cord blood CD34+ progenitor
      cells assayed both in vitro and after transplantation into NOD/SCID mice. Vectors
      pseudotyped with three different gammaretrovirus envelopes were used: the
      amphotropic MLV envelope (MLV-A), a modified gibbon ape leukemia virus envelope
      (GALV+), and a modified feline endogenous virus RD114 envelope (RDpro). Gene
      transfer to freshly thawed CD34+ cells in the absence of cytokines was very low.
      Addition of cytokines increased gene transfer efficiency significantly and this
      was further augmented if the cells were prestimulated for 24 h. Concentration of
      the vectors (15-fold) by low-speed centrifugation increased gene transfer to
      CD34+ cells in vitro even further. More than 90% of cells were transduced with a
      single exposure to the RDpro vector as determined by GFP expression using flow
      cytometry. The two other pseudotypes transduced approximately 65-70% of the cells
      under the same conditions. Transplantation of CD34+ cells prestimulated for 24 h
      and then transduced with a single exposure to concentrated vector revealed that
      the RDpro vector transduced 55.1% of NOD/SCID repopulating human cells, which was
      significantly higher than the MLV-A (12.6%)- or GALV+ (25.1%)-pseudotyped
      vectors.

PMID- 15727943
TI  - Inclusion of Jaagsiekte sheep retrovirus proviral elements markedly increases
      lentivirus vector pseudotyping efficiency.
AB  - Retroviral pseudotyping for gene transfer applications endeavors to alter vector
      tropism and maintain a suitable titer. We investigated the compatibility of the
      Jaagsiekte sheep retrovirus (JSRV) envelope glycoprotein with the feline
      immunodeficiency virus (FIV) vector. A construct consisting of the minimal JSRV
      env coding region expressed from a standard mammalian expression plasmid
      generated FIV vector titers of approximately 10(4) TU/ml following standard
      triple transfection, collection of supernatants, and concentration by centrifuge.
      Interestingly, retention of the native proviral 5' and 3' flanking regions
      surrounding the JSRV env resulted in exceptional titers of approximately 10(8)
      TU/ml following the same viral preparation. To discern the regions necessary to
      achieve this 10,000-fold increase in titer, additional constructs were designed
      and tested. Our results indicate that the enhanced vector titer correlates with
      an increase in steady-state levels of envelope RNA that results from a
      combination of RNA splicing and stability, leading to increased envelope protein
      production. Expression of four other glycoproteins in an expression plasmid
      retaining the enhancing elements from the JSRV proviral sequence increased FIV
      vector titers from 0- to 100-fold. These novel data demonstrate that optimization
      of the envelope expression construct can profoundly influence titers for
      lentivirus vectors.

PMID- 15727944
TI  - Lentiviral vectors pseudotyped with glycoproteins from Ross River and vesicular
      stomatitis viruses: variable transduction related to cell type and culture
      conditions.
AB  - HIV-1-derived lentiviral vectors have been pseudotyped with various envelope
      glycoproteins to alter their host range. Previously, we found that envelope
      glycoproteins derived from the alphavirus Ross River virus (RRV) can pseudotype
      lentiviral vectors and mediate efficient transduction of a variety of epithelial
      and fibroblast-derived cell lines. In this study, we have investigated
      transduction of hematopoietic cells using RRV-pseudotyped vectors encoding the
      enhanced green fluorescent protein (EGFP). RRV-mediated transduction of human
      CD34+ cord blood cells and progenitors was very inefficient, even at
      multiplicities of infection of 100 (0.4% EGFP-positive progenitor colonies).
      Inefficient transduction was also observed in a variety of hematopoietic cell
      lines. However, two erythroleukemia-derived cell lines and monocytic cells that
      were driven to macrophage-like differentiation were moderately transduced.
      Transduction of hematopoietic cells with a control VSV-G-pseudotyped lentiviral
      vector was generally efficient, but unexpectedly decreased up to threefold upon
      stimulation of lymphocytic cell lines or primary murine bone marrow cells. Also,
      the tested hematopoietic cell lines were essentially nonpermissive for adeno
      associated type 2 (AAV) vectors, and this was not affected by lineage, activity,
      or differentiation. Treatment of permissive 293 cells with proteases revealed
      that transduction with both the RRV- and the VSV-G-pseudotyped vectors in part
      depends on the presence of cell surface proteins. These results show a severely
      restricted ability of RRV glycoproteins to mediate transduction in hematopoietic
      cells that is likely due to specific receptor requirements that differ from those
      of VSV-G and AAV. Conversely, transduction with the VSV glycoprotein is affected
      by cellular activation more than widely believed. Our findings suggest that the
      envelope glycoproteins and culture conditions employed need to be carefully
      evaluated for each application. Furthermore, the uniquely restricted host range
      of RRV-pseudotyped vectors may aid in the design of novel cell-selective
      transduction strategies.

PMID- 15727946
TI  - Progression of vascular and neural dysfunction in sciatic nerves of Zucker
      diabetic fatty and Zucker rats.
AB  - We have examined the progression of vascular and neural deficits in Zucker rats,
      Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8
      to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at
      8 wk of age. The Zucker rats did not become hyperglycemic but were
      hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic
      by 8 wk of age. Through their life span, serum free fatty acids and triglycerides
      levels were significantly higher in Zucker and ZDF diabetic rats compared with
      age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was
      significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction
      velocity was significantly decreased after 12-14 wk of age in ZDF diabetic rats
      and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of
      epineurial arterioles of the sciatic nerve was impaired after 8-10 wk of age in
      ZDF diabetic rats and after approximately 16 wk of age in Zucker rats. In
      contrast, vascular relaxation mediated by calcitonin gene-related peptide was
      impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired
      in Zucker rats up to 40 wk of age. Markers of oxidative stress were
      differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate
      that vascular and neural dysfunction develops in both Zucker and ZDF diabetic
      rats but at different rates, which may be the result of hyperglycemia.

PMID- 15727947
TI  - A new polymorphism in the type II deiodinase gene is associated with circulating
      thyroid hormone parameters.
AB  - Type II deiodinase (D2) is important in the regulation of local thyroid hormone
      bioactivity in certain tissues. D2 in skeletal muscle may also play a role in
      serum triiodothyronine (T(3)) production. In this study, we identified a
      polymorphism in the 5'-UTR of the D2 gene (D2-ORFa-Gly3Asp). We investigated the
      association of D2-ORFa-Gly3Asp, and of the previously identified D2-Thr92Ala
      polymorphism, with serum iodothyronine levels. D2-ORFa-Gly3Asp was identified by
      sequencing the 5'-UTR of 15 randomly selected individuals. Genotypes for D2-ORFa
      Gly3Asp were determined in 156 healthy blood donors (age 46.3 +/- 12.2 yr) and
      349 ambulant elderly men (age 77.7 +/- 3.5 yr) and related to serum iodothyronine
      and TSH levels. D2-ORFa-Asp(3) had an allele frequency of 33.9% in blood bank
      donors and was associated with serum thyroxine (T(4); Gly/Gly vs. Gly/Asp vs.
      Asp/Asp = 7.06 +/- 0.14 vs. 6.74 +/- 0.15 vs. 6.29 +/- 0.27 microg/dl, P = 0.01),
      free T(4) (1.22 +/- 0.02 vs. 1.16 +/- 0.02 vs. 1.06 +/- 0.04 ng/dl, P = 0.001),
      reverse T(3) (P = 0.01), and T(3)/T(4) ratio (P = 0.002) in a dose-dependent
      manner, but not with serum T(3) (P = 0.59). In elderly men, D2-ORFa-Asp(3) had a
      similar frequency but was not associated with serum iodothyronine levels. This
      new polymorphism in the 5'-UTR of D2 is associated with iodothyronine levels in
      blood donors but not in elderly men. We hypothesize that this might be explained
      by the decline in skeletal muscle size during aging, resulting in a relative
      decrease in the contribution of D2 to serum T(3) production.

PMID- 15727948
TI  - Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1
      gene expression in brown adipose tissue.
AB  - A cluster of unique pathologies progressively develops during chronic total- or
      rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily
      observed symptoms are hyperphagia and decline in body weight. For body weight to
      be lost despite a severalfold increase in food consumption suggests that SD
      elevates metabolism as the subject enters a state of negative energy balance. To
      test the hypothesis that mediation of this hypermetabolism involves increased
      gene expression of uncoupling protein-1 (UCP1), which dissipates the
      thermodynamic energy of the mitochondrial proton-motive force as heat instead of
      ATP formation in brown adipose tissue (BAT), we 1) established the time course
      and magnitude of change in metabolism by measuring oxygen consumption, 2)
      estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and
      3) assayed serum leptin because of its role in regulating energy balance and food
      intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the
      platform (flowerpot) method, wherein muscle atonia during REM sleep causes
      contact with surrounding water and awakens it. By day 20, rats more than doubled
      food consumption while losing approximately 11% of body weight; metabolism rose
      to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive
      UCP1 over controls; serum leptin decreased and remained suppressed. The decline
      in leptin is consistent with the hyperphagic response, and we conclude that one
      of the mediators of elevated metabolism during prolonged REM-SD is increased gene
      expression of UCP1 in BAT.

PMID- 15727949
TI  - Growth hormone and testosterone interact positively to enhance protein and energy
      metabolism in hypopituitary men.
AB  - We investigated the impact of growth hormone (GH) alone, testosterone (T) alone,
      and combined GH and T on whole body protein metabolism. Twelve hypopituitary men
      participated in two studies. Study 1 compared the effects of GH alone with GH
      plus T, and study 2 compared the effects of T alone with GH plus T. IGF-I,
      resting energy expenditure (REE), and fat oxidation (F(ox)) and rates of whole
      body leucine appearance (R(a)), oxidation (L(ox)), and nonoxidative leucine
      disposal (NOLD) were measured. In study 1, GH treatment increased mean plasma IGF
      I (P < 0.001). GH did not change leucine R(a) but reduced L(ox) (P < 0.02) and
      increased NOLD (P < 0.02). Addition of T resulted in an additional increase in
      IGF-I (P < 0.05), reduction in Lox (P < 0.002), and increase in NOLD (P < 0.002).
      In study 2, T alone did not alter IGF-I levels. T alone did not change leucine
      R(a) but reduced L(ox) (P < 0.01) and increased NOLD (P < 0.01). Addition of GH
      further reduced L(ox) (P < 0.05) and increased NOLD (P < 0.05). In both studies,
      combined treatments on REE and F(ox) were greater than either alone. In summary,
      GH-induced increase of circulating IGF-I is augmented by T, which does not
      increase IGF-I in the absence of GH. T and GH exerted independent and additive
      effects on protein metabolism, F(ox) and REE. The anabolic effects of T are
      independent of circulating IGF-I.

PMID- 15727951
TI  - Is the renal production of erythropoietin controlled by the brain stem?
AB  - Although the structure and function of erythropoietin (Epo) are well documented,
      the mechanisms of the regulation of the renal synthesis of Epo are still poorly
      understood. Especially, the description of the localization and function of the
      O(2)-sensitive sensor regulating the renal synthesis of Epo is insufficient. A
      body of evidence suggests that extrarenal O(2)-sensitive sensors, localized
      particularly in the brain stem, play an important role in this connection. To
      support this concept, high cerebral pressure with consecutive hypoxia of the
      brain stem was generated by insufflation of synthetic cerebrospinal fluid into
      the catheterized cisterna magna of rats. When the cerebral pressure of the rats
      was above the level of their mean arterial blood pressure or the high cerebral
      pressure persisted for a longer period (>/=10 min), the Epo plasma concentration
      increased significantly. Bilateral nephrectomy or hypophysectomy before
      initiation of high intracranial pressure abolished this effect. Systemic
      parameters (heart rate, blood pressure, Pa(O(2)), Pa(CO(2)), arterial pH, renal
      blood flow, glucose concentration in blood) were not affected. Other stressors,
      like restricting the mobility of the rats, had no effect on Epo production.
      Hence, the effect of high cerebral pressure on renal synthesis of Epo seems to be
      specific. Increasing cerebral hydrostatic pressure leads to increased renal
      synthesis of Epo. Obviously, during hypoxia, cerebral O(2)-sensitive sensors
      release humoral factors, triggering the renal synthesis of Epo. The structure and
      function of these "Epo-releasing-factors" will have to be characterized in future
      experiments.

PMID- 15727950
TI  - Measurement of exogenous carbohydrate oxidation: a comparison of [U-14C]glucose
      and [U-13C]glucose tracers.
AB  - The purpose of this study was to assess the level of agreement between two
      techniques commonly used to measure exogenous carbohydrate oxidation (CHO(EXO)).
      To accomplish this, seven healthy male subjects (24 +/- 3 yr, 74.8 +/- 2.1 kg,
      V(O2(max)) 62 +/- 4 ml x kg(-1) x min(-1)) exercised at 50% of their peak power
      for 120 min on two occasions. During these exercise bouts, subjects ingested a
      solution containing either 144 g glucose (8.7% wt/vol glucose) or water. The
      glucose solution contained trace amounts of both [U-13C]glucose and [U
      14C]glucose to allow CHO(EXO) to be quantified simultaneously. The water trial
      was used to correct for background 13C enrichment. 13C appearance in the expired
      air was measured using isotope ratio mass spectrometry, whereas 14C appearance
      was quantified by trapping expired CO(2) in solution (using hyamine hydroxide)
      and adding a scintillator before counting radioactivity. CHO(EXO) measured with
      [13C]glucose ([13C]CHO(EXO)) was significantly greater than CHO(EXO) measured
      with [14C]glucose ([14C]CHO(EXO)) from 30 to 120 min. There was a 15 +/- 4%
      difference between [13C]CHO(EXO) and [14C]CHO(EXO) such that the absolute
      difference increased with the magnitude of CHO(EXO). Further investigations
      suggest that the difference is not because of losses of CO2 from the trapping
      solution before counting or an underestimation of the "strength" of the trapping
      solution. Previous research suggests that the degree of isotopic fractionation is
      small (S. C. Kalhan, S. M. Savin, and P. A. Adam. J Lab Clin Med89: 285-294,
      1977). Therefore, the explanation for the discrepancy in calculated CHO(EXO)
      remains to be fully understood.

PMID- 15727952
TI  - Impaired fatty acid metabolism in type 2 diabetic skeletal muscle cells is
      reversed by PPARgamma agonists.
AB  - The impact of type 2 diabetes on the ability of muscle to accumulate and dispose
      of fatty acids and triglycerides was evaluated in cultured muscle cells from
      nondiabetic (ND) and type 2 diabetic (T2D) subjects. In the presence of 5 microM
      palmitate, T2D muscle cells accumulated less lipid than ND cells (11.5 +/- 1.2
      vs. 15.1 +/- 1.4 nmol/mg protein, P < 0.05). Chronic treatment (4 days) with the
      peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist troglitazone
      increased palmitate accumulation, normalizing uptake in T2D cells. There were no
      significant differences between groups with regard to the relative incorporation
      of palmitate into neutral lipid species. This distribution was also unaffected by
      troglitazone treatment. beta-Oxidation of both long-chain (palmitate) and medium
      chain (octanoate) fatty acids in T2D muscle cells was reduced by approximately
      40% compared with ND cells. Palmitate oxidation occurred primarily in
      mitochondrial ( approximately 40-50% of total) and peroxisomal (20-30%)
      compartments. The diabetes-related defect in palmitate oxidation was localized to
      the mitochondrial component. Both palmitate and octanoate oxidation were
      stimulated by a series of thiazolidinediones. Oxidation in T2D muscle cells was
      normalized after treatment. Troglitazone increased the mitochondrial component of
      palmitate oxidation. Skeletal muscle cells from T2D subjects express defects in
      free fatty acid metabolism that are retained in vitro, most importantly defects
      in beta-oxidation. These defects can be corrected by treatment with PPARgamma
      agonists. Augmentation of fatty acid disposal in skeletal muscle, potentially
      reducing intramyocellular triglyceride content, may represent one mechanism for
      the lipid-lowering and insulin-sensitizing effects of thiazolidinediones.

PMID- 15727953
TI  - No effects of lifelong creatine supplementation on sarcopenia in senescence
      accelerated mice (SAMP8).
AB  - Oral creatine supplementation can acutely ameliorate skeletal muscle function in
      older humans, but its value in the prevention of sarcopenia remains unknown. We
      evaluated the effects of lifelong creatine supplementation on muscle mass and
      morphology, contractility, and metabolic properties in a mouse model of muscle
      senescence. Male senescence-accelerated mice (SAMP8) were fed control or creatine
      supplemented (2% of food intake) diet from the age of 10 to 60 wk. Soleus and
      extensor digitorum longus muscles were tested for in vitro contractile
      properties, creatine content, and morphology at weeks 25 and 60. Both muscle
      types showed reduced phosphocreatine content at week 60 that could not be
      prevented by creatine. Accordingly, age-associated decline in muscle mass and
      contractility was not influenced by treatment. Aged soleus muscles had fewer and
      smaller fast-twitch glycolytic fibers irrespective of treatment received. It is
      concluded that lifelong creatine supplementation is no effective strategy to
      prevent sarcopenia in senescence-accelerated mice.

PMID- 15727954
TI  - Joint synchrony of reciprocal hormonal signaling in human paradigms of both ACTH
      excess and cortisol depletion.
AB  - The hypothalamo-pituitary-adrenal axis is a stress-adaptive neuroendocrine
      ensemble, in which adrenocorticotropin (ACTH) drives cortisol secretion
      (feedforward) and cortisol restrains ACTH outflow (feedback). Quantifying
      direction- and pathway-specific adjustments within this and other interlinked
      systems by noninvasive means remains difficult. The present study tests the
      hypothesis that forward and reverse cross-approximate entropy (X-ApEn), a lag-,
      scale-, and model-independent measure of two-signal synchrony, would allow
      quantifiable discrimination of feedforward (ACTH --> cortisol) and feedback
      (cortisol --> ACTH) control. To this end, forward X-ApEn was defined by employing
      serial ACTH concentrations as a template to appraise pair-wise synchrony with
      cortisol secretion rates and vice versa for reverse X-ApEn. Coupled hormone
      profiles included normal ACTH-normal cortisol, high ACTH-high cortisol, and high
      ACTH-low cortisol concentrations in 35 healthy subjects, 21 patients with tumoral
      ACTH secretion, and 9 volunteers given placebo and a steroidogenic inhibitor,
      respectively. We used forward and reverse X-ApEn analyses to identify marked and
      equivalent losses of feedforward and feedback linkages (both P < 0.001) in
      patients with tumoral ACTH secretion. An identical analytical strategy revealed
      that ACTH --> cortisol feedforward synchrony decreases (P < 0.001), whereas
      cortisol --> ACTH feedback synchrony increases (P < 0.001), in response to
      hypocortisolemia. The collective outcomes establish precedence for pathway
      specific adaptations in a major neurohormonal system. Thus quantification of
      directionally defined joint synchrony of biologically coupled signals offers a
      noninvasive strategy to dissect feedforward- and feedback-selective adaptations
      in an interactive axis.

PMID- 15727955
TI  - Mother nature as treatment for ADHD: overstating the benefits of green.

PMID- 15727957
TI  - Bioterrorism preparedness: potential threats remain.

PMID- 15727958
TI  - Bioterrorism preparedness funds well used at the local level.

PMID- 15727960
TI  - Editorial independence at the journal.

PMID- 15727961
TI  - Racial identity among Hispanics: implications for health and well-being.

PMID- 15727962
TI  - Promoting health for transgender women: Transgender Resources and Neighborhood
      Space (TRANS) program in San Francisco.
AB  - Transgender women are at high risk for HIV, substance abuse, and mental health
      problems. We describe a health promotion intervention program tailored to
      transgender women in San Francisco. The program creates a safe space for
      providing transgender-sensitive education about HIV risk reduction, substance
      abuse prevention, and general health promotion. Transgender health educators
      conduct workshops and make referrals to appropriate substance abuse treatment
      programs and other services in the community. Evaluation findings indicate that
      this community-tailored intervention may be an effective way to reach transgender
      women and reduce sexual risk behaviors, depression, and perceived barriers to
      substance abuse treatment.

PMID- 15727963
TI  - Health care policy issues as a result of the genetic revolution: implications for
      public health.
AB  - The genetic revolution has spawned 4 distinct issues of universal importance to
      health care policy and society: genetic privacy, regulation and standardization
      of genetic tests, gene patenting, and education. Adequate policy advancements for
      these 4 areas are lacking. Stringent controls must be placed on individual health
      records to prevent their misuse. Genetic testing within the clinical setting
      should undergo thorough evaluation before it is implemented. Regulations are
      needed to prevent the monopolization of DNA sequences. Society and health care
      professionals must be educated about the scope of genetic testing because current
      trends indicate that genetic and molecular assessments are destined to become a
      routine component of health care.

PMID- 15727964
TI  - Biological basis of determinants of health.
AB  - Clinical medicine and health policy planning find common cause as they seek to
      define the determinants of health. There is substantial recent interest in the
      social ecology in which health is embedded. However, biology is where these
      contributing environmental factors are translated. I provide a new conceptual
      framework for the biological determinants of health. The old public health rubric
      of host, agent, and environment as the features that define the root elements of
      health is an impoverished scheme, because it does not represent our new
      appreciation of genetic and aging contributions to phenotypic health. I propose
      genes, external agency, internal agency, and aging as more operationally helpful
      determinants that effectively describe the biological experience of the organism.
      This scheme has the advantage of differentiating those agencies that are
      practically approachable, and therefore deserving of increased attention and
      investment, and those that are currently intractable.

PMID- 15727965
TI  - Human biomonitoring to optimize fish consumption advice: reducing uncertainty
      when evaluating benefits and risks.
AB  - National fish consumption advisories that are based solely on assessment of risk
      of exposure to contaminants without consideration of consumption benefits result
      in overly restrictive advice that discourages eating fish even in areas where
      such advice is unwarranted. In fact, generic fish advisories may have adverse
      public health consequences because of decreased fish consumption and substitution
      of foods that are less healthy. Public health is on the threshold of a new era
      for determining actual exposures to environmental contaminants, owing to
      technological advances in analytical chemistry. It is now possible to target fish
      consumption advice to specific at-risk populations by evaluating individual
      contaminant exposures and health risk factors. Because of the current epidemic of
      nutritionally linked disease, such as obesity, diabetes, and cardiovascular
      disease, general recommendations for limiting fish consumption are ill conceived
      and potentially dangerous.

PMID- 15727966
TI  - Smoke-free airlines and the role of organized labor: a case study.
AB  - Labor unions play an important role in debates about smoke-free worksites. We
      investigated the role of flight attendants and their unions in creating smoke
      free air travel. We used case study methodology to search tobacco industry
      documents and labor union periodicals and to interview key informants (i.e.,
      people identified as having first-hand information and experience in the campaign
      to make airlines smoke free). We then compared findings across these data
      sources. Tobacco industry strategies against the establishment of smoke-free
      worksites failed in the case of airlines, largely because of the efforts of
      flight attendants and their unions. Other factors contributed to the failure but
      likely would have been insufficient to derail industry efforts without strong
      stands by the flight attendants. This case illustrates the potential for
      successful partnerships between unions and tobacco control policy advocates when
      developing smoke-free worksite policies.

PMID- 15727967
TI  - Integrating occupational safety and health information into vocational and
      technical education and other workforce preparation programs.
AB  - The high rates of injury among young workers are a pressing public health issue,
      especially given the demand of the job market for new workers. Young and new
      workers experience the highest rates of occupational injuries of any age group.
      Incorporating occupational safety and health (OSH) information into the more than
      20 000 vocational and other workforce preparation programs in the United States
      might provide a mechanism for reducing work-related injuries and illnesses among
      young and new workers. We assessed the status of including OSH information or
      training in workforce preparation programs and found there is an inconsistent
      emphasis on OSH information.

PMID- 15727968
TI  - A model designed to enhance informed consent: experiences from the HIV prevention
      trials network.
AB  - HIV prevention research in developing countries has resulted in increased
      attention to and discussion of ethical issues, particularly the issue of the
      quality of informed consent. We present a conceptual framework for an enhanced
      informed consent process, drawing on experiences garnered from domestic and
      international studies conducted by the HIV Prevention Trials Network, funded by
      the National Institutes of Health. This framework guides the development of an
      informed consent process designed to help ensure initial and continued
      comprehension of research participation, with an emphasis on HIV prevention
      research. Attention is focused at the individual and community levels and on 3
      study phases: preenrollment, enrollment, and postenrollment.

PMID- 15727969
TI  - Implementation of a smoke-free policy on school premises and tobacco control as a
      priority among municipal health promotion activities: nationwide survey in Japan.
AB  - We conducted a nationwide survey to evaluate the effect of implementing a smoke
      free policy in municipalities that forbid teachers to smoke on school premises.
      Questionnaires were mailed to 3207 municipalities throughout Japan. After we
      adjusted for population size and the standardized mortality ratio for male lung
      cancer, we found that assigning a high priority to tobacco control in municipal
      health promotion activities was significantly associated with implementation of
      school tobacco-control policies (odds ratio = 1.50, 95% confidence interval=1.24,
      1.81).

PMID- 15727970
TI  - Fall-induced deaths among elderly people.
AB  - Falls and fall-induced injuries in older people are a major public health problem
      in modern societies with aging populations. Injury is the fifth leading cause of
      death in older adults, and most of these fatal injuries are related to falls. We
      have assessed the nationwide trends in fall-induced deaths of older people in
      Finland for more than 3 decades (1971-2002), and the results showed that the
      number of fall-induced deaths among elderly Finns is clearly increasing,
      especially among men.

PMID- 15727971
TI  - Evidence of a dose-response relationship between "truth" antismoking ads and
      youth smoking prevalence.
AB  - OBJECTIVES: In early 2000, the American Legacy Foundation launched the national
      "truth" campaign, the first national antismoking campaign to discourage tobacco
      use among youths. We studied the impact of the campaign on national smoking rates
      among US youths (students in grades 8, 10, and 12). METHODS: We used data from
      the Monitoring the Future survey in a pre/post quasi-experimental design to
      relate trends in youth smoking prevalence to varied doses of the "truth" campaign
      in a national sample of approximately 50000 students in grades 8, 10, and 12,
      surveyed each spring from 1997 through 2002. RESULTS: Findings indicate that the
      campaign accounted for a significant portion of the recent decline in youth
      smoking prevalence. We found that smoking prevalence among all students declined
      from 25.3% to 18.0% between 1999 and 2002 and that the campaign accounted for
      approximately 22% of this decline. CONCLUSIONS: This study showed that the
      campaign was associated with substantial declines in youth smoking and has
      accelerated recent declines in youth smoking prevalence.

PMID- 15727972
TI  - Effectiveness of school programs in preventing childhood obesity: a multilevel
      comparison.
AB  - OBJECTIVES: In light of the alarming increase in childhood obesity and lack of
      evidence for the effectiveness of school programs, we studied the effects of
      school programs in regard to preventing excess body weight. METHODS: In 2003, we
      surveyed 5200 grade 5 students along with their parents and school principals. We
      measured height and weight, assessed dietary intake, and collected information on
      physical and sedentary activities. We compared excess body weight, diet, and
      physical activity across schools with and without nutrition programs using
      multilevel regression methods while adjusting for gender and socioeconomic
      characteristics of parents and residential neighborhoods. RESULTS: Students from
      schools participating in a coordinated program that incorporated recommendations
      for school-based healthy eating programs exhibited significantly lower rates of
      overweight and obesity, had healthier diets, and reported more physical
      activities than students from schools without nutrition programs. CONCLUSIONS:
      Our finding that school programs are effective in preventing childhood obesity
      supports the need for broader implementation of successful programs, which will
      reduce childhood obesity and, in the longer term, comorbid conditions and health
      care spending.

PMID- 15727973
TI  - Exemptions to school immunization requirements: the role of school-level
      requirements, policies, and procedures.
AB  - OBJECTIVES: Our goal was to determine whether school-level variability in
      implementation of immunization requirements is associated with the likelihood of
      a child having received an exemption to school immunization requirements.
      METHODS: We surveyed 1000 school immunization personnel in Colorado,
      Massachusetts, Missouri, and Washington. We explored associations between school
      implementation of immunization requirements and the likelihood of a child having
      an exemption using logistic regression models. RESULTS: School policies
      associated with an increased likelihood of children having exemptions included
      lack of provision of written instructions for completing the school immunization
      requirement before enrollment, administrative procedures making it easier to
      claim an exemption, and granting of philosophical exemptions. In the 2 states we
      surveyed where philosophical exemptions are not authorized (Massachusetts and
      Missouri), 17.0% and 18.1% of schools reported permitting philosophical
      exemptions. CONCLUSIONS: Inconsistencies in the interpretation and implementation
      of school immunization laws contribute to variability in rates of exemptions.
      School policies should be reviewed to ensure consistency with the intent of state
      laws.

PMID- 15727975
TI  - Persistence of effects of the Checkpoints program on parental restrictions of
      teen driving privileges.
AB  - OBJECTIVES: We describe intervention effects on parent limits on novice teenage
      driving. METHODS: We recruited parents and their 16-year-old children (n = 469)
      with learner's permits and randomized them from August 2000 to March 2003.
      Intervention families received persuasive newsletters related to high-risk
      teenage driving and a parent-teenager driving agreement; comparison families
      received standard information on driver safety. We conducted interviews when the
      adolescents obtained a learner's permit, upon licensure, and at 3, 6, and 12
      months postlicensure. RESULTS: Intervention parents and teenagers reported
      stricter limits on teen driving compared with the comparison group at 12 months,
      with direct effects through 3 months and indirect effects through 12 months
      postlicensure. CONCLUSIONS: A simple behavioral intervention was efficacious in
      increasing parental restriction of high-risk teen driving conditions among newly
      licensed drivers.

PMID- 15727974
TI  - The state sets the rate: the relationship among state-specific college binge
      drinking, state binge drinking rates, and selected state alcohol control
      policies.
AB  - OBJECTIVES: We assessed the relationship between college binge drinking, binge
      drinking in the general population, and selected alcohol control policies.
      METHODS: We analyzed binge drinking rates from 2 national surveys, the Harvard
      School of Public Health College Alcohol Study and the Centers for Disease Control
      and Prevention's Behavioral Risk Factor Surveillance System. Binge drinking data
      were linked to a summary measure of 7 salient alcohol control policies and a
      rating of resources devoted to law enforcement. RESULTS: State-level college and
      adult binge drinking rates were strongly correlated (Pearson correlation
      coefficient=0.43; P<.01). Attending college in states with the lowest binge
      drinking rates (adjusted odds ratio [OR]=0.63; 95% confidence interval [CI]=0.41,
      0.97) and presence of more stringent alcohol control policies (adjusted OR=0.57;
      95% CI=0.33, 0.97) were independent predictors of student binge drinking, after
      adjusting for state law enforcement and individual-, college-, and state-level
      covariates. CONCLUSIONS: State of residence is a predictor of binge drinking by
      college students. State-level alcohol control policies may help reduce binge
      drinking among college students and in the general population.

PMID- 15727976
TI  - Moderate alcohol use and depression in young adults: findings from a national
      longitudinal study.
AB  - OBJECTIVES: We examined the association between moderate alcohol use and
      depressive mood among young adults before and after adjustment for demographic,
      health, and socioeconomic factors that may act as confounders. METHODS: We
      analyzed 2 waves of interview data collected from 13892 young adults who
      participated in the National Longitudinal Study of Adolescent Health to compare
      frequency of depressive symptoms in moderate drinkers with frequency of symptoms
      in young adults in other alcohol use categories. RESULTS: With adjustment for
      health and socioeconomic factors, frequency of depressive symptoms were similar
      among moderate drinkers, lifetime and long-term abstainers, and heavy/heavier
      moderate drinkers but remained significantly higher among heavy drinkers.
      CONCLUSIONS: Moderate alcohol use may have no effect on depression in young
      adults relative to abstinence from alcohol use.

PMID- 15727977
TI  - Longitudinal patterns and predictors of alcohol consumption in the United States.
AB  - OBJECTIVES: We examined demographic predictors of longitudinal patterns in
      alcohol consumption. METHODS: We used mixed-effects models to describe individual
      alcohol consumption and change in consumption with age, as well as the
      associations between consumption and birth year, national alcohol consumption,
      and demographic factors, among 14 105 adults from the National Health and
      Nutrition Examination Survey I Epidemiologic Follow-Up Study. RESULTS: Alcohol
      consumption declined with increasing age, and individual consumption mirrored
      national consumption. Higher consumption was associated with male gender, being
      White, being married, having a higher educational level, having a higher income,
      being employed, and being a smoker. Faster age-related decline in consumption was
      associated with earlier cohorts, being male, being married, having a lower
      educational level, and being a smoker. CONCLUSIONS: Compared with alcohol
      consumption among earlier cohorts, that among recent cohorts declined more slowly
      with increasing age, suggesting that negative health effects of alcohol could
      increase in the future.

PMID- 15727978
TI  - Relationship between drug abuse and intimate partner violence: a longitudinal
      study among women receiving methadone.
AB  - OBJECTIVES: We examined whether frequent drug use increases the likelihood of
      subsequent sexual or physical intimate partner violence (IPV) and whether IPV
      increases the likelihood of subsequent frequent drug use. METHODS: A random
      sample of 416 women on methadone was assessed at baseline (wave 1) and at 6
      months (wave 2), and 12 months (wave 3) following the initial assessment.
      Propensity score matching and multiple logistic regression were employed.
      RESULTS: Women who reported frequent crack use at wave 2 were more likely than
      non-drug using women to report IPV at wave 3 (odds ratio [OR]=4.4; 95% confidence
      interval [CI]=2.1, 9.1; P<.01), and frequent marijuana users at wave 2 were more
      likely than non-drug users to report IPV at wave 3 (OR=4.5; 95% CI=2.4, 8.4;
      P<.01). In addition, women who reported IPV at wave 2 were more likely than women
      who did not report IPV to indicate frequent heroin use at wave 3 (OR=2.7; 95%
      CI=1.1, 6.5; P=.04). CONCLUSIONS: Our findings suggest that the relationship
      between frequent drug use and IPV is bidirectional and varies by type of drug.

PMID- 15727979
TI  - Homicide: a leading cause of injury deaths among pregnant and postpartum women in
      the United States, 1991-1999.
AB  - OBJECTIVES: We identified risk factors for pregnancy-associated homicide (women
      who died as a result of homicide during or within 1 year of pregnancy) in the
      United States from 1991 to 1999. METHODS: Pregnancy-associated homicides were
      analyzed with data from the Pregnancy Mortality Surveillance System at the
      Centers for Disease Control and Prevention. RESULTS: Six hundred seventeen (8.4%)
      homicide deaths were reported to the Pregnancy Mortality Surveillance System. The
      pregnancy-associated homicide ratio was 1.7 per 100000 live births. Risk factors
      included age younger than 20 years, Black race, and late or no prenatal care.
      Firearms were the leading mechanism for homicide (56.6%). CONCLUSIONS: Homicide
      is a leading cause of pregnancy-associated injury deaths.

PMID- 15727980
TI  - Underreporting of maternal deaths on death certificates and the magnitude of the
      problem of maternal mortality.
AB  - OBJECTIVES: I studied the extent to which maternal deaths are underreported on
      death certificates. METHODS: We collected data on maternal deaths from death
      certificates, linkage of death certificates with birth and fetal death records,
      and review of medical examiner records. RESULTS: Thirty-eight percent of maternal
      deaths were unreported on death certificates. Half or more deaths were unreported
      for women who were undelivered at the time of death, experienced a fetal death or
      therapeutic abortion, died more than a week after delivery, or died as a result
      of a cardiovascular disorder. CONCLUSIONS: The number of maternal deaths is
      substantially underestimated when death certificates alone are used to identify
      deaths, and it is unlikely that the Healthy People 2010 objective of reducing the
      maternal mortality rate to no more than 3.3 deaths per 100000 live births by 2010
      can be achieved. Increasing numbers of births to older women and multiple
      gestation pregnancies are likely to complicate efforts to reduce maternal
      mortality.

PMID- 15727981
TI  - Work-related pain and injury and barriers to workers' compensation among Las
      Vegas hotel room cleaners.
AB  - OBJECTIVES: We examined the prevalence of work-related pain and injury and
      explored barriers to and experiences of reporting among workers. METHODS: We
      surveyed 941 unionized hotel room cleaners about work-related pain, injury,
      disability, and reporting. RESULTS: During the past 12 months, 75% of workers in
      our study experienced work-related pain, and 31% reported it to management; 20%
      filed claims for workers' compensation as a result of work-related injury, and
      35% of their claims were denied. Barriers to reporting injury included "It would
      be too much trouble" (43%), "I was afraid" (26%), and "I didn't know how" (18%).
      An estimated 69% of medical costs were shifted from employers to workers.
      CONCLUSIONS: The reasons for underreporting and the extent of claim denial
      warrant further investigation. Implications for worker health and the precise
      quantification of shifting costs to workers also should be addressed.

PMID- 15727982
TI  - In their own words: lessons learned from those exposed to anthrax.
AB  - OBJECTIVES: We evaluated perceptions of workers at the US Postal Service
      Brentwood Processing and Distribution Center and US Senate employees regarding
      public health responses to the anthrax mailings of October 2001. We generated
      recommendations for improving responses to bioterrorism on the basis of the
      perceptions we recorded. METHODS: Transcripts from focus groups conducted with
      Brentwood and US Senate employees were examined, and qualitative analysis
      identified common domains. RESULTS: Brentwood focus groups consisted of 36
      participants (97% African American and 19% hearing impaired). US Senate focus
      groups consisted of 7 participants (71% White and 0% hearing impaired). The focus
      groups revealed that participants' trust in public health agencies had eroded and
      that this erosion could threaten the effectiveness of communication during future
      public health emergencies. Among Brentwood participants, lack of trust involved
      the perception that unfair treatment on the basis of race/ethnicity and
      socioeconomic status had occurred; among US Senate participants, it derived from
      perceptions of inconsistent and disorganized messages. CONCLUSIONS: Effective
      communication during a public health emergency depends on the provision of clear
      messages and close involvement of the affected community. Diverse populations may
      require individualized approaches to ensure that messages are delivered
      appropriately. Special attention should be given to those who face barriers to
      traditional modes of communication.

PMID- 15727983
TI  - Racial/ethnic discrimination and common mental disorders among workers: findings
      from the EMPIRIC Study of Ethnic Minority Groups in the United Kingdom.
AB  - OBJECTIVES: We measured perceived discrimination and its association with common
      mental disorders among workers in the United Kingdom. METHODS: We conducted a
      secondary analysis of a national sample of 6 ethnic groups (n=2054).
      Discrimination was measured as reports of insults; unfair treatment at work; or
      job denial stemming from race, religion, or language. The outcome assessed was
      presence of common mental disorders. RESULTS: The risk of mental disorders was
      highest among ethnic minority individuals reporting unfair treatment (odds ratio
      [OR]=2.0; 95% confidence interval [CI]=1.2, 3.2) and racial insults (OR=2.3; 95%
      CI=1.4, 3.6). The overall greatest risks were observed among Black Caribbeans
      exposed to unfair treatment at work (OR=2.9; 95% CI=1.2, 7.3) and Indian (OR=3.1;
      95% CI=1.4, 7.2), Bangladeshi (OR=32.9; 95% CI=2.5, 436.0), and Irish (OR=2.9;
      95% CI=1.1, 7.6) individuals reporting insults. CONCLUSIONS: Racial/ethnic
      discrimination shows strong associations with common mental disorders.

PMID- 15727984
TI  - Lack of evidence of sexual transmission of hepatitis C virus in a prospective
      cohort study of men who have sex with men.
AB  - OBJECTIVES: We studied the prevalence and incidence of hepatitis C virus (HCV)
      infection in the ongoing Omega Cohort Study of men who have sex with men (MSM).
      METHODS: From January to September 2001, consenting men (n = 1085) attending a
      follow-up visit to the ongoing Omega Cohort Study were tested for HCV. If the
      test results were positive for HCV, we compared them with test results from
      previous serum samples collected from the time of entry into the original cohort
      study to determine the time of infection. RESULTS: HCV prevalence at entry was
      2.9% and was strongly associated with injection drug use (32.9% vs 0.3%,
      P<.0001). Only 1 seroconversion was identified in 2653 person-years of follow-up
      (incidence rate = 0.038 per 100 person-years). The seroconverter was an active
      injection drug user who reported needle sharing. CONCLUSIONS: Sexual transmission
      of HCV among MSM appears to be rare.

PMID- 15727986
TI  - Inclusion of people with disabilities in telephone health surveillance surveys.
AB  - OBJECTIVES: Telephone survey data are widely used to describe population health,
      but some fear that people with disabilities cannot participate. We tested the
      hypothesis that a telephone survey would underrepresent adults with disabilities,
      and that the adults with disabilities who responded would report lower
      prevalences of sensory, mental, self-care, and multiple limitations than those
      observed in people with disabilities in the general population. METHODS: We
      compared characteristics of adults with disabilities identified by the 2001
      Washington State Behavioral Risk Factor Surveillance Survey (BRFSS) to Washington
      adults with disabilities in the Census 2000 Supplementary Survey (C2SS), to 2
      BRFSS Disability Supplements, and to the Washington State Population Survey. All
      except the C2SS are telephone surveys. RESULTS: Contrary to expectations, post
      hoc analyses of all telephone surveys found significantly higher prevalence of
      disability in the Washington adult population than did the C2SS. The hypothesis
      of more sensory, mental, and self-care limitation in telephone disability samples
      was supported in only 2 of 11 instances in which a disability sample was asked
      about 1 of these limitations. Findings were not explained by differences in
      disability definition or type of informant. CONCLUSIONS: These results suggest
      that population telephone surveys do not underrepresent adults with disabilities.
      The counterintuitive finding of their higher survey participation raises further
      questions.

PMID- 15727985
TI  - The influence of breast self-examination on subsequent mammography participation.
AB  - OBJECTIVES: We evaluated whether breast self-examination (BSE) influences
      subsequent mammography participation. METHODS: We evaluated associations between
      BSE and subsequent mammography participation, adjusting for baseline screening
      behaviors and sociodemographic, health, and lifestyle characteristics, among
      women aged 40 years and older using data from the longitudinal Canadian National
      Population Health Survey. RESULTS: Regular performance of BSE at baseline was not
      associated with receipt of a recent mammogram at follow-up among all women
      (adjusted odds ratio [OR]=1.01; 95% confidence interval [CI]= 0.75, 1.35) or with
      mammography uptake among the subgroup of women reporting never use at baseline
      (adjusted OR=0.78; 95% CI=0.50, 1.22). CONCLUSIONS: The lack of association
      between performance of BSE and subsequent mammography participation suggests that
      not recommending BSE is unlikely to influence mammography participation.

PMID- 15727987
TI  - Natural mentoring relationships and adolescent health: evidence from a national
      study.
AB  - OBJECTIVES: We used nationally representative data to examine the impact of
      natural (or informal) mentoring relationships on health-related outcomes among
      older adolescents and young adults. METHODS: We examined outcomes from Wave III
      of the National Longitudinal Study of Adolescent Health as a function of whether
      or not respondents reported a mentoring relationship. Logistic regression was
      used with control for demographic variables, previous level of functioning, and
      individual and environmental risk. RESULTS: Respondents who reported a mentoring
      relationship were more likely to exhibit favorable outcomes relating to
      education/work (completing high school, college attendance, working >/= 10 hours
      a week), reduced problem behavior (gang membership, hurting others in physical
      fights, risk taking), psychological well-being (heightened self-esteem, life
      satisfaction), and health (physical activity level, birth control use). However,
      effects of exposure to individual and environmental risk factors generally were
      larger in magnitude than protective effects associated with mentoring.
      CONCLUSIONS: These findings suggest a broad and multifaceted impact of mentoring
      relationships on adolescent health. However, mentoring relationships alone are
      not enough to meet the needs of at-risk youths and therefore should be
      incorporated into more comprehensive interventions.

PMID- 15727988
TI  - Quantification of K+ secretion through apical low-conductance K channels in the
      CCD.
AB  - Outward and inward currents through single small-conductance K(+) (SK) channels
      were measured in cell-attached patches of the apical membrane of principal cells
      of the rat cortical collecting duct (CCD). Currents showed mild inward
      rectification with high [K(+)] in the pipette (K(p)(+)), which decreased as
      K(p)(+) was lowered. Inward conductances had a hyperbolic dependence on K(p)(+)
      with half-maximal conductance at approximately 20 mM. Outward conductances,
      measured near the reversal potential, also increased with K(p)(+) from 15 pS
      (K(p)(+) = 0) to 50 pS (K(p)(+) = 134 mM). SK channel density was measured as the
      number of conducting channels per patch in cell-attached patches. As reported
      previously, channel density increased when animals were on a high-K diet for 7
      days. Addition of 8-cpt-cAMP to the bath at least 5 min before making a seal
      increased SK channel density to an even greater extent, although this increase
      was not additive with the effect of a high-K diet. In contrast, increases in Na
      channel activity, assessed as the whole cell amiloride-sensitive current, due to
      K loading and 8-cpt-cAMP treatment were additive. Single-channel conductances and
      channel densities were used as inputs to a simple mathematical model of the CCD
      to predict rates of transepithelial Na(+) and K(+) transport as a function of
      apical Na(+) permeability and K(+) conductance, basolateral pump rates and K(+)
      conductance, and the paracellular conductance. With measured values for these
      parameters, the model predicted transport rates that were in good agreement with
      values measured in isolated, perfused tubules. The number and properties of SK
      channels account for K(+) transport by the CCD under all physiological conditions
      tested.

PMID- 15727989
TI  - Selective permeability barrier to urea in shark rectal gland.
AB  - Elasmobranchs such as the dogfish shark Squalus acanthius achieve osmotic
      homeostasis by maintaining urea concentrations in the 300- to 400-mM range, thus
      offsetting to some degree ambient marine osmolalities of 900-1,000
      mosmol/kgH(2)O. These creatures also maintain salt balance without losing urea by
      secreting a NaCl-rich (500 mM) and urea-poor (18 mM) fluid from the rectal gland
      that is isotonic with the plasma. The composition of the rectal gland fluid
      suggests that its epithelial cells are permeable to water and not to urea.
      Because previous work showed that lipid bilayers that permit water flux do not
      block flux of urea, we reasoned that the plasma membranes of rectal gland
      epithelial cells must either have aquaporin water channels or must have some
      selective barrier to urea flux. We therefore isolated apical and basolateral
      membranes from shark rectal glands and determined their permeabilities to water
      and urea. Apical membrane fractions were markedly enriched for Na-K-2Cl
      cotransporter, whereas basolateral membrane fractions were enriched for Na-K
      ATPase. Basolateral membrane osmotic water permeability (P(f)) averaged 4.3 +/-
      1.3 x 10(-3) cm/s, whereas urea permeability averaged 4.2 +/- 0.8 x 10(-7) cm/s.
      The activation energy for water flow averaged 16.4 kcal/mol. Apical membrane P(f)
      averaged 7.5 +/- 1.6 x 10(-4) cm/s, and urea permeability averaged 2.2 +/- 0.4 x
      10(-7) cm/s, with an average activation energy for water flow of 18.6 kcal/mol.
      The relatively low water permeabilities and high activation energies argue
      strongly against water flux via aquaporins. Comparison of membrane water and urea
      permeabilities with those of artificial liposomes and other isolated biological
      membranes indicates that the basolateral membrane urea permeability is fivefold
      lower than would be anticipated for its water permeability. These results
      indicate that the rectal gland maintains a selective barrier to urea in its
      basolateral membranes.

PMID- 15727990
TI  - Resistance to oxidative stress by chronic infusion of angiotensin II in mouse
      kidney is not mediated by the AT2 receptor.
AB  - Wild-type mice are resistant to ANG II-induced renal injury and hence form an
      attractive model to study renal defense against ANG II. The present study tested
      whether ANG II induces expression of antioxidative genes via the AT2 receptor in
      renal cortex and thereby counteracts prooxidative forces. ANG II was infused in
      female C57BL/6J mice for 28 days and a subgroup received AT2 receptor antagonist
      (PD-123,319) for the last 3 days. ANG II induced hypertension and aortic
      hypertrophy; proteinuria and renal injury were absent. Urinary nitric oxide
      metabolites (NOx) were decreased, and lipid peroxide (TBARS) excretion remained
      unchanged. Expression of NADPH oxidase components was decreased in renal cortex
      but induced in aorta. Heme oxygenase-1 (HO-1) was induced in both renal cortex
      and aorta. In contrast, ANG II suggestively increased AT2 receptor expression in
      kidney but not in aorta. AT2 receptor blockade enhanced hypertension in ANG II
      infused mice, reversed ANG II effects on NOx excretion, but did not affect TBARS.
      Despite its prohypertensive effect, expression of prooxidative genes in the renal
      cortex decreased rather than increased after short-term AT2 receptor blockade and
      renal HO-1 induction after ANG II was normalized. Thus chronic ANG II infusion in
      mice induces hypertension but not oxidative stress. In contrast to the response
      in aorta, gene expression of components of NADPH-oxidase was not enhanced in
      renal cortex. Although ANG II administration induced renal cortical AT2 receptor
      expression, blockade of that receptor did not unveil the AT2 receptor as
      intrarenal dampening factor of prooxidative forces.

PMID- 15727991
TI  - Presence of the nucleic acid channel in renal brush-border membranes: allosteric
      modulation by extracellular calcium.
AB  - We have previously described a cell surface channel complex that is highly
      selective for nucleic acid (6, 7). The channel complex was purified to
      homogeneity by solubilizing renal brush-border membranes (BBM) with CHAPS and
      separation by liquid chromatography. It was characterized by reconstitution in
      planar lipid bilayers. The channel consists of a pore-forming subunit that is
      blocked by heparan sulfate and a regulatory subunit that is blocked by L-malate
      (7). The current studies were performed to compare the characteristics of the
      nucleic acid-conducting channel in native BBM with the characteristics that have
      been determined for the complex reconstituted from purified proteins. BBM were
      purified by differential centrifugation and reconstituted in lipid bilayers.
      Current was not observed until oligodeoxynucleotide (ODN) was added. Conductance
      was 9.1 +/- 0.9 pS; rectification and voltage dependence were not observed.
      Reversal potential (E(rev)) shifted to +14 +/- 0.1 mV by a 10-fold gradient for
      ODN but was not altered when gradients were created for any other ion. Open
      probability increased significantly with an increase in Ca(2+) on the trans
      chamber of the bilayer apparatus. Changes in cis Ca(2+) were without effect.
      Addition of L-malate to the cis chamber or heparan sulfate to the trans chamber
      significantly reduced the open probability of the channel. These data demonstrate
      that the nucleic acid channel in BBM is electrophysiologically and
      pharmacologically identical to that previously reported for purified protein and
      demonstrate that a nucleic acid-conducting channel is a component of renal BBM.

PMID- 15727993
TI  - Phrenic nerve hemangioblastoma in a von Hippel-Lindau patient.

PMID- 15727994
TI  - Radiation-induced fibrosis of the spermatic cord: sonographic and MRI findings.

PMID- 15727995
TI  - Renal cell carcinoma visible only during the corticomedullary phase of
      enhancement.

PMID- 15727996
TI  - Metastatic adenocarcinoma presenting as monoarticular arthritis of the knee.

PMID- 15727997
TI  - Primary squamous cell carcinoma: an incidental toe mass.

PMID- 15727998
TI  - Obturator neuropathy caused by an acetabular labral cyst: MRI findings.

PMID- 15727999
TI  - Preoperative embolization of vascular phyllodes tumor of the breast.

PMID- 15728000
TI  - Transhepatic portal venous power-pulse spray rheolytic thrombectomy for acute
      portal vein thrombosis after CT-guided pancreas biopsy.

PMID- 15728001
TI  - Malignant fibrous histiocytoma of the pharynx.

PMID- 15728002
TI  - Gastric perforation after percutaneous radiofrequency ablation of a colorectal
      liver metastasis in a patient with adhesions in the peritoneal cavity.

PMID- 15728003
TI  - Percutaneous balloon angioplasty of superior mesenteric artery stenosis in an
      adolescent.

PMID- 15728004
TI  - Palliative radiofrequency ablation of a fungating, symptomatic breast lesion.

PMID- 15728005
TI  - Pre- and postoperative MRI of esophageal and gastric leiomyomatosis in a
      pediatric patient.

PMID- 15728006
TI  - Neonatal obstructive jaundice caused by a malpositioned gastrostomy tube.

PMID- 15728007
TI  - Sonography and CT of vasculitis during gemcitabine therapy.

PMID- 15728009
TI  - MDCT of coronary artery aneurysms.

PMID- 15728008
TI  - Detection of an intrathymic parathyroid adenoma using single-photon emission CT
      99mTc sestamibi scintigraphy and CT.

PMID- 15728010
TI  - Bilateral supraorbital masses after prolonged headlock injury: an unusual
      manifestation of orbital subperiosteal hematomas.

PMID- 15728011
TI  - LEOPARD syndrome: cardiac imaging findings.

PMID- 15728012
TI  - MRI of mycotic sinus of valsalva pseudoaneurysm secondary to Aspergillus
      pericarditis.

PMID- 15728013
TI  - Demonstration of complex coronary-pulmonary artery fistula by MDCT and
      correlation with coronary angiography.

PMID- 15728014
TI  - Bronchial anthracofibrosis and tuberculosis: CT features before and after
      treatment.

PMID- 15728015
TI  - Multifocal micronodular pneumocyte hyperplasia in tuberous sclerosis.

PMID- 15728016
TI  - Partially uncrossed pyramidal tracts shown by tractography in horizontal gaze
      palsy and scoliosis.

PMID- 15728017
TI  - Radiographic appearance of a catheter-free wireless esophageal pH probe.

PMID- 15728018
TI  - Clip migration within 15 days of 11-gauge vacuum-assisted stereotactic breast
      biopsy.

PMID- 15728019
TI  - Concentric rings within a breast mass on sonography: lamellated keratin in an
      epidermal inclusion cyst.

PMID- 15728020
TI  - In vivo sonography through an open MRI breast coil to correlate sonographic and
      MRI findings.

PMID- 15728021
TI  - Metastatic choriocarcinoma to the breast: appearance on mammography and Doppler
      sonography.

PMID- 15728022
TI  - Antegrade ileography for evaluating a distal anastomotic stricture after loop
      ileostomy.

PMID- 15728023
TI  - Gastrointestinal stromal tumor with metastases in an adult woman treated with
      imatinib mesylate: MDCT findings.

PMID- 15728024
TI  - Prospective CT diagnosis of stump appendicitis.

PMID- 15728025
TI  - Gastrocolic fistula with migration of feeding tube into transverse colon as a
      complication of percutaneous endoscopic gastrostomy.

PMID- 15728026
TI  - Benign omental hemangiopericytoma presenting with hemoperitoneum: radiologic
      findings.

PMID- 15728027
TI  - Determination and follow-up of striolenticular vasodilatation and hyperemia after
      acute embolic stroke: demonstration on MR angiography.

PMID- 15728028
TI  - Pylephlebitis after CT-guided percutaneous liver biopsy.

PMID- 15728029
TI  - Paraprosthetic extravasation of enteric contrast: a rare and direct sign of
      secondary aortoenteric fistula.

PMID- 15728030
TI  - CT appearance of a retained "fish" in the abdomen.

PMID- 15728031
TI  - Pancreatoblastoma in an adult woman: sonography, CT, and dynamic gadolinium
      enhanced MRI features.

PMID- 15728032
TI  - Fluid-fluid levels in cavernous hemangiomas of the liver: baffled?

PMID- 15728033
TI  - Primary non-Hodgkin's lymphoma of the gallbladder.

PMID- 15728034
TI  - Double gallbladder diagnosed on contrast-enhanced MR cholangiography with
      mangafodipir trisodium.

PMID- 15728035
TI  - Thoracoabdominal muscular enlargement in dermatomyositis: CT visualization.

PMID- 15728036
TI  - CT findings of pelvic lipomatosis of nerve.

PMID- 15728037
TI  - Retroperitoneal fibrosis involving the left kidney in a patient with a remote
      history of Riedel's thyroiditis.

PMID- 15728038
TI  - Delayed traumatic bladder rupture.

PMID- 15728039
TI  - Sevoflurane but not propofol preserves myocardial function during minimally
      invasive direct coronary artery bypass surgery.
AB  - Volatile anesthetics exert cardioprotective properties in experimental and
      clinical studies. We designed this study to investigate the effects of
      sevoflurane on left ventricular (LV) performance during minimally invasive direct
      coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. Fifty
      two patients scheduled for MIDCAB surgery were randomly assigned to a propofol or
      a sevoflurane group. Apart from the anesthetics used, there was no difference in
      surgical and anesthetic management. After determination of cardiac troponin T,
      creatine kinase, and creatine kinase MB, electrocardiographic (ECG) data and
      echocardiography variables (myocardial performance index and early to atrial
      filling velocity ratio) the left anterior descending coronary artery (LAD) was
      clamped until anastomosis with the left internal mammary artery was completed.
      During LAD occlusion and during reperfusion, echocardiography measurements were
      repeated. Blood samples were obtained repeatedly for up to 72 h. After LAD
      occlusion, myocardial performance index and early to atrial filling velocity
      ratio in the propofol group deteriorated significantly from 0.40 +/- 0.12 and
      1.29 +/- 0.35 to 0.49 +/- 0.10 and 1.13 +/- 0.22, respectively, whereas there was
      no change in the sevoflurane group. In the propofol group myocardial performance
      index remained increased (0.47 +/- 0.11) compared with baseline during
      reperfusion. There were no significant differences in ECG and laboratory values
      between groups. In conclusion, during a brief period of ischemia in patients
      undergoing MIDCAB surgery, sevoflurane preserved myocardial function better than
      propofol.

PMID- 15728040
TI  - Hemodynamic effects of portal triad clamping with and without pneumoperitoneum:
      an echocardiographic study.
AB  - The decrease of cardiac index observed during portal triad clamping (PTC) with
      and without pneumoperitoneum has been studied only with right heart
      catheterization. To better understand this decrease of cardiac index, we
      investigated the balance between the adequacy of preload and the ability of the
      heart to pump against an increased afterload, by using transesophageal
      echocardiography. Ten patients with PTC performed during laparoscopy and 10 with
      PTC performed during laparotomy were studied. Five minutes after PTC, the stroke
      volume, the left ventricular (LV) fractional area change (FAC), and the LV end
      systolic wall stress (LVESWS) were measured as the conventional hemodynamic
      variables. Regional wall motion abnormalities (RWMA) were also recorded. In the
      laparotomy group, LV end-diastolic area decreased, and LVESWS did not increase
      significantly. FAC remained stable, and one patient developed RWMA. In the
      laparoscopic group, LV end-diastolic area remained stable, and LVESWS increased.
      FAC decreased significantly, and five patients developed RWMA. A decrease in
      preload was the main important change in the laparotomy group, and in the
      laparoscopic group a decrease in LV function was demonstrated that was likely a
      consequence of decreased LV preload and increased LV afterload. However, these
      did not necessitate stopping the procedure or releasing PTC in these study
      patients without cardiac disease.

PMID- 15728041
TI  - An anatomic landmark to simplify subclavian vein cannulation: the "deltoid
      tuberosity".
AB  - The subclavian vein is frequently used to obtain central venous access. Several
      landmarks exist to determine the puncture site and angle, but they may require
      patient manipulation and anatomic measurements. We studied the feasibility of
      using the deltoid tuberosity, located on the lateral aspect of the clavicle, as
      an anatomic landmark. This would not necessitate these maneuvers and could
      therefore facilitate subclavian vein access. To systematically investigate this
      landmark, we conducted a study in four phases: 1) Two blindfolded examiners
      determined the distance between the tuberosity's medial border and the clavicle's
      lateral end in 100 dried clavicles and then 2) performed subclavian vein
      cannulation in 20 fresh human cadavers using the tuberosity and the suprasternal
      notch as landmarks. 3) Three-dimensional reconstructions of the subclavian artery
      and vein and surrounding structures were derived from computed tomography
      datasets of 10 patients. The length of the path of a virtual subclavian vein
      cannulation with the deltoid tuberosity landmark was measured bilaterally. 4) In
      a prospective, randomized trial, subclavian vein cannulation was performed in 60
      patients with a standard approach or with the deltoid tuberosity as landmark.
      Interobserver difference between measurements in phase 1 was 3 +/- 1 mm (mean +/-
      sd); subclavian vein cannulation was achieved in 19 of 20 cases, whereas the
      subclavian artery was cannulated in one case (phase 2). In phase 3, there was no
      significant difference in skin-vein distance between the left (4.9 +/- 0.5 cm)
      and right (4.7 +/- 0.6 cm) sides. In phase 4, subclavian vein cannulation could
      be performed in all patients; moreover, subclavian vein cannulation was
      significantly (P < 0.01) faster in the deltoid tuberosity group versus the
      standard approach group (23 +/- 16 versus 34 +/- 14 s). We conclude that the
      clavicle's tuberosity may reflect an alternative anatomic landmark to simplify
      subclavian vein cannulation by minimizing patient manipulation and anatomic
      measurements.

PMID- 15728042
TI  - The effects of dexmedetomidine on left ventricular function during hypoxia and
      reoxygenation in isolated rat hearts.
AB  - Hypoxia resulting from apnea in patients with sleep apnea is an important factor
      in heart disease. We designed the present study to determine whether
      dexmedetomidine (DEX) has a direct protective effect against hypoxia
      reoxygenation-induced left ventricular dysfunction without systemic hemodynamic
      and humoral effects. Isolated rat hearts were exposed to 60-min hypoxia followed
      by 30-min reoxygenation with 0, 10, or 100 nM DEX prehypoxia administration (n =
      7 each group). In a second experiment (n = 7), 100 nM DEX was administered
      posthypoxia. In a third experiment (n = 7 each group), an alpha 2 antagonist,
      yohimbine was given with and without 100 nM DEX prehypoxia administration. DEX
      prehypoxia, but not posthypoxia, administration significantly improved the
      recovery of left ventricular developed pressure after reoxygenation (0, 10, 100
      nM DEX prehypoxia or 100 nM DEX posthypoxia values were 53 +/- 6, 64 +/- 9, 78 +/
      13, or 62 +/- 12 mm Hg [mean +/- sd]) and reversed by yohimbine, 58 +/- 8 mm Hg,
      respectively. We conclude that DEX exerts the direct protective effect on the
      left ventricular dysfunction caused by hypoxia-reoxygenation through mainly alpha
      2-adrenergic stimulation before and during the hypoxic period.

PMID- 15728043
TI  - Angiotensin system inhibitors in a general surgical population.
AB  - We studied the relationship between the timing of discontinuing chronic
      angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor
      subtype 1 antagonists (ARA) and hypotension after the induction of general
      anesthesia in a general surgical population. We retrospectively studied 267
      hypertensive patients receiving chronic ACEI/ARA therapy undergoing elective
      noncardiac surgery under general anesthesia. During preoperative visits, patients
      were asked to either take their last ACEI/ARA therapy on the morning of surgery
      or withhold it up to 24 h before surgery. The number of hours from the last
      ACEI/ARA dose to surgery was recorded during the preoperative interview.
      Electronic medical and anesthesia records were reviewed for comorbidities, type
      and dose of anesthetics used, intraoperative hemodynamics, IV fluids,
      perioperative vasopressor administration, and rate of severe postoperative
      complications. Arterial blood pressure (BP) and heart rate were recorded during
      the 60-min postinduction period, and hypotension was classified as moderate
      (systolic BP <or=85 mm Hg) and severe (systolic BP <or=65 mm Hg). We analyzed all
      variables separately for patients who took their last ACEI/ARA therapy <10 h and
      >or=10 h before surgery. During the first 30 min after anesthetic induction,
      moderate hypotension was more frequent in patients whose most recent ACEI/ARA
      therapy was taken <10 h (60%) compared with those who stopped it >or=10 h (46%)
      before induction (P = 0.02). The adjusted odds ratio for moderate hypotension was
      1.74 (95% confidence interval, 1.03-2.93) for those who took their ACEI/ARA
      therapy <10 h before surgery (P = 0.04). There were no differences between groups
      in the incidence of severe hypotension, nor was there a difference in the use of
      vasopressors. During the 31-60 min after induction, the incidence of either
      moderate (P = 0.43) or severe (P = 0.97) hypotension was similar in the two
      groups. No differences in postoperative complications were found between groups.
      In conclusion, discontinuation of ACEI/ARA therapy at least 10 h before
      anesthesia was associated with a reduced risk of immediate postinduction
      hypotension.

PMID- 15728044
TI  - Intraoperative blood salvage: fluid replacement calculations.
AB  - Intraoperative blood salvage (IBS) devices are used as adjuncts to blood
      conservation in spinal surgical procedures of increasing duration, complexity,
      and total blood loss. We applied existing information about the performance and
      efficiency of IBS devices together with existing information regarding the
      distribution of crystalloids and colloids to provide clinicians with guidelines
      for the prediction of the total blood loss implications of a given volume of IBS
      return. We also developed guidelines for estimation of the appropriate
      replacement volumes for the acellular component of blood loss when replacement is
      undertaken with either isotonic-iso-oncotic colloid or isotonic crystalloid
      solutions. When average hematocrit during blood loss is between 25% and 30%,
      total blood loss will be 3.4-4.0 times the volume of the IBS recovery. When
      replacement is undertaken with colloids or crystalloids, the appropriate
      replacement volume will be approximately 2.5 and 8.0 (respectively) times the
      volume of the IBS recovery. These volumes may be larger than have been
      appreciated by some clinicians.

PMID- 15728045
TI  - Goldilocks: the pediatric anesthesiologist's dilemma.

PMID- 15728046
TI  - Awareness during anesthesia in children: a prospective cohort study.
AB  - During routine adult anesthesia, the risk of awareness is 0.1%-0.2%. No recent
      studies have reported the incidence in children. Altered pharmacology and
      differing anesthesia techniques suggest that the incidence may differ in
      children. In this prospective cohort study, we determined the incidence of
      awareness during anesthesia in children. Eight-hundred-sixty-four children aged 5
      12 yr who had undergone general anesthesia at The Royal Children's Hospital were
      interviewed on 3 occasions to determine the incidence of awareness. The awareness
      assessment was nested within a larger study of behavior change after anesthesia.
      Reports of suspected awareness were sent to four independent adjudicators. If
      they all agreed, a case was classified as true awareness. Twenty-eight reports
      were generated. There were 7 cases of true awareness, for an incidence of 0.8%
      (95% confidence interval, 0.3%-1.7%). Only one aware child received neuromuscular
      blockers, compared with 12% in the nonaware group. No aware child reported
      distress, and no substantial difference was detected in behavior disturbance
      between aware (20%) and nonaware (16%) children. The data provide some evidence
      that, like adults, children are also at risk of intraoperative awareness.
      Although the cause remains unclear, anesthesiologists should be alerted to the
      possibility of awareness in children.

PMID- 15728047
TI  - Threshold current of an insulated needle in the intrathecal space in pediatric
      patients.
AB  - A threshold current of <1 mA has been suggested to be sufficient to produce a
      motor response to electrical stimulation in the intrathecal space. We designed
      this study to determine the threshold current needed to elicit motor activity for
      an insulated needle in the intrathecal space. Twenty pediatric patients aged 7.3
      +/- 3.9 yr scheduled for lumbar puncture were recruited. After sedation with
      propofol, patients were turned to the lateral position and an 18-gauge or 20
      gauge introducer needle was placed at the L4-5 level through which an insulated
      24-gauge Pajunck unipolar needle (with a Sprotte tip and stylet) was inserted.
      The needle was advanced into the intrathecal space as suggested by the presence
      of a "pop." At this point, a nerve stimulator was attached to the insulated
      needle and the current was gradually increased until motor activity was evident.
      The needle hub was checked for cerebrospinal fluid. If cerebrospinal fluid was
      not present, the needle was advanced further until cerebrospinal fluid was
      present. The threshold current was retested. The mean current in the intrathecal
      space required to elicit a motor response was 0.6 +/- 0.3 mA (range, 0.1-1 mA).
      In 19 patients, the twitches were observed at the L4-5 myotomes and 1 patient had
      twitches at L2. Twitches were observed unilaterally in 19 children and
      bilaterally in one child. This confirms the hypothesis that the threshold current
      in the intrathecal space is <1 mA and that it differs significantly from the
      threshold currents reported for electrical stimulation in the epidural space.

PMID- 15728048
TI  - Advances in diabetic management: implications for anesthesia.
AB  - The past 20 yr have seen an explosion in advances for the management of Type I
      diabetes mellitus. Not only new delivery systems, such as the continuous
      subcutaneous insulin pump, but also better and more stable types of insulin with
      predictable pharmacokinetics and pharmacodynamics have been developed. An
      artificial pancreas is now on the horizon. This progress has had a significant
      impact on modern perioperative care of the diabetic patient.

PMID- 15728049
TI  - The use of a laryngeal mask airway for emergent airway management in a prone
      child.
AB  - A 5-yr-old girl with Arnold-Chiari Malformation, Type 1, was accidentally
      tracheally extubated while positioned prone in a Mayfield neurosurgical headrest
      during a decompressive craniectomy and cervical laminectomy. While preparations
      were being made to return the patient to the supine position for reintubation, we
      placed a laryngeal mask airway (LMA) without difficulty. The child was kept in
      the prone position with the LMA in place using positive-pressure ventilation for
      the remainder of the operation. This case report emphasizes the practical,
      emergent use of a LMA to secure the airway of a pediatric patient in the prone
      position after accidental extubation.

PMID- 15728050
TI  - Hyperkalemic cardiac arrest after cardiopulmonary bypass in a child with
      unsuspected duchenne muscular dystrophy.
AB  - Adverse reactions to volatile anesthetics and depolarizing muscle relaxants can
      occur in patients with Duchenne muscular dystrophy (DMD) resulting in acute
      rhabdomyolysis and hyperkalemia. We report a case of hyperkalemic cardiac arrest
      after cardiac surgery using cardiopulmonary bypass in a child with unsuspected
      DMD. Early diagnosis and management of hyperkalemia resulted in a successful
      outcome. Genetic testing confirmed the diagnosis of DMD. We recommend a thorough
      preoperative investigation, including creatine kinase estimation, in children
      with a history of unexplained motor delay.

PMID- 15728051
TI  - Preoperative intravenous fluid therapy decreases postoperative nausea and pain in
      high risk patients.
AB  - The potential for preoperative IV rehydration to reduce postoperative nausea and
      vomiting (PONV) and pain in patients undergoing ambulatory surgery remains
      unclear, with conflicting results reported. We sought to determine whether
      preoperative IV rehydration with a balanced salt solution would decrease the
      incidence of PONV in patients at increased risk for these symptoms. Eighty ASA
      grade I-III patients presenting for gynecologic laparoscopy were randomized to
      receive large (2 mL/kg per hour fasting) or small (3 mL/kg) volume infusions of
      compound sodium lactate solution over 20 min preoperatively. A standardized
      balanced anesthetic was used. The incidence and severity of PONV and pain, and
      need for supplemental antiemetic and analgesic therapy, were assessed by a
      blinded investigator at 0.5, 1, and 4 h postoperatively, and on the first and
      third postoperative days. The incidence (control 87% versus large volume 59%) and
      severity of PONV were significantly reduced in the large volume infusion group at
      all time intervals. The large volume infusion group also had decreased
      postoperative pain scores and required less supplemental analgesia. Preoperative
      correction of intravascular volume deficits effectively reduces PONV and
      postoperative pain in high risk patients presenting for ambulatory surgery. We
      recommend the preoperative administration of 2 mL/kg of compound sodium lactate
      for every hour of fasting to patients with an increased PONV risk presenting for
      ambulatory surgery.

PMID- 15728052
TI  - Bacteriostatic saline containing benzyl alcohol decreases the pain associated
      with the injection of propofol.
AB  - Bacteriostatic saline is a physiological saline solution containing the
      bacteriostatic agent benzyl alcohol as a 0.9% solution. It is used mostly for
      diluting and dissolving drugs for IV injection and as a flush for intravascular
      catheters. It also has local anesthetic properties. We studied its efficacy in
      decreasing the pain associated with IV administration of propofol and compared it
      with mixing lidocaine with propofol. One-hundred-twenty patients were randomly
      allocated into three groups. All patients received propofol 50 mg. The benzyl
      alcohol group received bacteriostatic saline as a preinjection, and the lidocaine
      group received propofol containing lidocaine. The placebo group did not receive
      bacteriostatic saline or lidocaine. Fifteen of 39 patients (38%) in the benzyl
      alcohol group complained of pain on injection compared to 33 of 39 (84%) in the
      placebo group and 22 of 42 (52%) in the lidocaine group. Differences were
      significant between the benzyl alcohol and placebo groups (P < 0.01) and the
      lidocaine and placebo groups (P < 0.01). Preinjection with bacteriostatic saline
      decreases the incidence of pain associated with IV administration of propofol and
      is comparable to that of mixing lidocaine with propofol.

PMID- 15728053
TI  - Dexmedetomidine decreases the convulsive potency of bupivacaine and
      levobupivacaine in rats: involvement of alpha2-adrenoceptor for controlling
      convulsions.
AB  - Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is used in
      combination with local anesthetics for sedation and analgesia. We tested the
      hypothesis that dexmedetomidine used for sedation alters the convulsive potency
      of racemic bupivacaine and levobupivacaine in awake, spontaneously breathing
      rats. In the first experiments, male Sprague-Dawley rats were randomly divided
      into six groups: bupivacaine with no dexmedetomidine (bupivacaine control; BC),
      bupivacaine with small-dose dexmedetomidine (BS), bupivacaine with large-dose
      dexmedetomidine (BL), levobupivacaine with no dexmedetomidine (levobupivacaine
      control; LC), levobupivacaine with small-dose dexmedetomidine (LS), and
      levobupivacaine with large-dose dexmedetomidine (LL) (n = 10 for each group).
      Continuous infusion of dexmedetomidine (Groups BC and LC, 0 microg x kg(-1) x h(
      1); Groups BS and LS, 3.6 microg x kg(-1) x h(-1); and Groups BL and LL, 10.8
      microg x kg(-1) x h(-1)) was started after bolus injection (Groups BC and LC, 0
      microg/kg; Groups BS and LS, 0.5 microg/kg; and Groups BL and LL, 1.5 microg/kg).
      Fifteen minutes after the start of the dexmedetomidine infusion, continuous
      infusion of bupivacaine (Groups BC, BS, and BL) or levobupivacaine (Groups LC,
      LS, and LL) at 1 mg x kg(-1) x min(-1) was started and continued until
      tonic/clonic convulsions occurred. Dexmedetomidine achieved significantly
      different sedation levels both in Groups BC, BS, and BL and in Groups LC, LS, and
      LL (P < 0.05). Convulsive doses of bupivacaine and levobupivacaine were
      significantly larger in Groups BL and LL than in Groups BC and LC, respectively
      (P < 0.01 for both). Concentrations of bupivacaine and levobupivacaine in plasma
      and in brain at the onset of convulsions were also larger in Groups BL and LL
      than in Groups BC and LC (P < 0.01 for both). In the second experiment, yohimbine
      (1 mg/kg) administered 10 min before and 5 min after the start of dexmedetomidine
      infusion completely reversed the sedative effect of dexmedetomidine (bolus 1.5
      microg/kg, followed by 10.8 microg x kg(-1) x h(-1)). Convulsive doses and plasma
      and brain concentrations of bupivacaine and levobupivacaine at the onset of
      convulsions in rats receiving yohimbine and dexmedetomidine were significantly
      smaller than in those receiving only dexmedetomidine (P < 0.05 for all) and were
      similar to those without dexmedetomidine or yohimbine. We conclude that
      dexmedetomidine used for sedation decreases the convulsive potency of both
      bupivacaine and levobupivacaine in rats. Alpha(2)-adrenoceptor agonism may be
      involved in this anticonvulsant potency.

PMID- 15728054
TI  - Airway reflexes return more rapidly after desflurane anesthesia than after
      sevoflurane anesthesia.
AB  - Patients given a more soluble inhaled anesthetic usually take longer to awaken
      from anesthesia than do patients given a less soluble anesthetic. In the present
      study, we tested whether such a delay in awakening was also associated with a
      delay in restoration of protective airway reflexes. Patients were randomly
      assigned to receive desflurane (n = 31) or sevoflurane (n = 33) via a laryngeal
      mask airway. Demographics did not differ between groups. The average minimum
      alveolar anesthetic concentration fraction for both groups was 0.62, and the mean
      (+/-sd) minimum alveolar anesthetic concentration hours was 1.00 +/- 0.68 for
      desflurane versus 0.95 +/- 0.57 for sevoflurane, although more patients given
      sevoflurane also received regional anesthesia (17 for sevoflurane and 8 for
      desflurane). The time from stopping anesthetic administration to appropriate
      response to command was longer after sevoflurane (5.5 +/- 3.1 versus 3.4 +/- 1.9
      min; P < 0.01). In addition, the time from first response to command to ability
      to swallow 20 mL of water without coughing or drooling was longer after
      sevoflurane. At 2 min after responding to command, all patients given desflurane
      were able to swallow without coughing or drooling, whereas 55% of patients given
      sevoflurane coughed and/or drooled (P < 0.001). At 6 min after responding to
      command, 18% of patients given sevoflurane still could not swallow without
      coughing or drooling (P < 0.05). We conclude that desflurane allows an earlier
      return of protective airway reflexes.

PMID- 15728055
TI  - Sedation with GPI 15715, a water-soluble prodrug of propofol, using target
      controlled infusion in volunteers.
AB  - GPI 15715 is the first water-soluble propofol prodrug that has been studied in
      humans. Present propofol lipid formulations have well known undesirable
      properties, for example, pain on injection and increased triglyceride
      concentrations. We investigated whether GPI 15715 is suitable to achieve and
      maintain moderate sedation for 2 h. Six male and six female volunteers received a
      target-controlled infusion of GPI 15715, with an initial propofol target
      concentration of 1.8 microg/mL and the possibility to adjust the propofol target
      once after 1 h. Propofol concentrations, the bispectral index, and modified
      Observer's Assessment of Alertness/Sedation Scale (MOAA/S) scores were monitored.
      The median MOAA/S score was 4 during the first hour and was 3 during the second
      hour of infusion. The propofol target had to be changed to 2.4 microg/mL in seven
      volunteers and to 3.0 microg/mL in two volunteers. A propofol concentration of
      1.9 microg/mL had the highest probability to result in an MOAA/S score of 3,
      which corresponds with moderate sedation. We observed no serious side effects. We
      conclude that GPI 15715 produces excellent sedation.

PMID- 15728056
TI  - Enantioselective actions of bupivacaine and ropivacaine on coronary vascular
      resistance at cardiotoxic concentrations.
AB  - The main concern with the use of the long-acting local anesthetics bupivacaine
      and ropivacaine is inadvertent IV injection, which exposes the heart to toxic
      drug concentrations. We tested the hypothesis that these chiral anesthetics exert
      enantioselective actions on coronary vascular tone, the regulation of which does
      not involve voltage-gated Na(+) channels. Coronary perfusion pressure (CPP) was
      continuously measured in isolated hearts perfused via the aorta at a constant
      flow rate. This method provides a sensitive assay of coronary vascular resistance
      in the intact heart. In parallel experiments, we examined the effects of
      bupivacaine and ropivacaine on intracellular [Ca(2+)] in coronary endothelial
      cells. In addition, the effect of bupivacaine on mitochondrial membrane potential
      was assessed using isolated ventricular myocytes. Racemic bupivacaine and R(+)
      bupivacaine produced similar dose-dependent decreases in CPP. However, S(-)
      bupivacaine, S(-)-ropivacaine and R(+)-ropivacaine increased CPP. In contrast to
      adenosine triphosphate, neither racemic bupivacaine nor S(-)-ropivacaine changed
      endothelial intracellular [Ca(2+)], suggesting that these clinically used drugs
      do not modulate endothelial nitric oxide synthase. We also showed that the
      putative uncoupler bupivacaine did not depolarize mitochondria in intact
      ventricular myocytes. In conclusion, the long-acting local anesthetics have
      enantioselective actions on coronary resistance vessels. Racemic bupivacaine and
      R(+)-bupivacaine are coronary vasodilators, whereas S(-)-bupivacaine, S(-)
      ropivacaine and, to a lesser extent, R(+)-ropivacaine all induce coronary
      vasoconstriction.

PMID- 15728057
TI  - A novel molecule (frakefamide) with peripheral opioid properties: the effects on
      resting ventilation compared with morphine and placebo.
AB  - In animal models frakefamide (FF) is a potent analgesic that acts as a peripheral
      active mu-selective receptor agonist. In this double-blind, randomized, double
      dummy four-way crossover study in 12 healthy male subjects, we investigated the
      effects on resting ventilation of FF and 2 dose levels of morphine compared with
      placebo. Each drug was infused for 6 h. The subjects received 1.22 mg/kg FF, 0.43
      mg/kg morphine (M-large), and 0.11 mg/kg morphine (M-small). Sodium chloride 9
      mg/mL was used as placebo. Ventilation was measured by pneumotachography and
      inline capnography. Blood was collected and plasma concentrations of FF and
      morphine and its metabolites were analyzed. Within 15 min after administration of
      FF all subjects complained of a transient myalgia, which disappeared within 30
      min. At target measurement (335 min), there were no differences in tidal volume
      among the groups. Respiratory rates were, however, slower in the two M-groups (P
      < 0.05 in M-small and P < 0.001 in M-large) compared with FF and placebo. Minute
      volume was significantly less in the M-large group compared with the FF (P <
      0.01) and placebo (P < 0.01) groups. This difference was reflected by an elevated
      ETco(2) in the M-large group (P < 0.01). We conclude that, during resting
      ventilation, FF, unlike morphine, did not cause central respiratory depression.
      This suggests that FF has only peripheral mu-opioid agonist activity in humans.

PMID- 15728058
TI  - Dominance of the hand does not change the phonomyographic measurement of
      neuromuscular block at the adductor pollicis muscle.
AB  - Phonomyography (PMG) is a novel method to determine neuromuscular blockade (NMB)
      with high sensitivity and applicability at all muscles. The adductor pollicis
      muscle has long been used in research and clinical practice as reference for
      neuromuscular monitoring. The goal of our study was to compare PMG signals (train
      of-four [TOF] ratios and T(1)/T(0) values) from both hands of the same patient to
      investigate the influence of hand dominance on neuromuscular monitoring. In 14
      patients, PMG was recorded via small piezoelectric microphones taped over the
      thenar mass of both hands. After induction of anesthesia, both ulnar nerves were
      stimulated supramaximally using TOF stimulation every 12 s. Mivacurium 0.2 mg/kg
      was administered within 5 s. Onset, maximum effect, and offset of NMB were
      compared between both adductor pollicis muscles. Twelve patients were right
      handed and two patients were left-handed. No statistical difference was found
      between the signals from the dominant or nondominant hand. Correlation was very
      good (r = 0.95). Agreement was excellent with a bias of -0.57% and limits of
      agreement of -17.9% to 16.7% (dominant - nondominant hand). This study shows
      minimal bias, good correlation and no statistical difference when NMB is
      monitored at both the dominant and nondominant adductor pollicis muscles. Both
      hands could be used interchangeably to assess NMB at the adductor pollicis
      muscle.

PMID- 15728059
TI  - Extravasation injury in the perioperative setting.
AB  - Extravasation is an unintentional injection or leakage of fluid in the
      perivascular or subcutaneous space. Extravasation injury results from a
      combination of factors, including solution cytotoxicity, osmolality,
      vasoconstrictor properties, infusion pressure, regional anatomical peculiarities,
      and other patient factors. We reviewed the hospital files of patients who had
      sustained a significant extravasation injury in the perioperative setting at two
      German hospitals. These cases highlight the risk of devastating consequences from
      extravasation injury. Vasoactive drugs and hyperosmolar and concentrated
      electrolyte solutions are the predominant vesicants in the perioperative setting.
      Prompt and appropriate intervention is important for avoiding or minimizing
      extensive tissue injury.

PMID- 15728060
TI  - Epidural ropivacaine anesthesia decreases the bispectral index during the awake
      phase and sevoflurane general anesthesia.
AB  - The sedative effects of epidural anesthesia without volatile and IV anesthetics
      and quantification of the degree of epidural anesthesia-induced sedation have not
      been investigated. In the current study we evaluated the effects of epidural
      anesthesia on the bispectral index (BIS) during the awake phase and during
      general anesthesia. After placing the epidural catheter, the patients were
      randomly allocated to 2 groups receiving either 5 mL of epidural saline (group S)
      or the same volume of 0.75% ropivacaine (group R). The BIS measurements during
      the awake phase were performed at 7, 12, 13, 14, 22, and 23 min after the
      epidural injection. General anesthesia was then induced with propofol and
      vecuronium and maintained with 0.75% sevoflurane. From approximately 10 min after
      tracheal intubation, the BIS measurements were made at 1-min intervals for 10
      min. The BIS during the awake phase was significantly lower in group R than in
      group S (P < 0.05). The BIS during general anesthesia was significantly lower in
      group R than in group S (P < 0.0001). Epidural anesthesia decreased the BIS
      during the awake phase and during general anesthesia. The decrease of the BIS
      associated with epidural anesthesia was more prominent during general anesthesia
      than during the awake phase.

PMID- 15728061
TI  - The short-acting beta1-adrenoceptor antagonists esmolol and landiolol suppress
      the bispectral index response to tracheal intubation during sevoflurane
      anesthesia.
AB  - In this randomized, double-blind, controlled study, we tested the hypothesis that
      the short-acting beta(1)-adrenoceptor antagonists esmolol and landiolol suppress
      hemodynamic changes and bispectral index (BIS) increases, both of which are
      induced by tracheal intubation under general anesthesia with sevoflurane alone.
      Forty-five patients were randomly assigned to the control, esmolol, and landiolol
      groups (n = 15 each). Anesthesia was induced with sevoflurane in oxygen, with an
      end-tidal concentration maintained at 1 minimum alveolar anesthetic concentration
      (MAC). Infusion of saline (control group), esmolol (bolus of 1 mg/kg and then
      0.25 mg x kg(-1) x min(-1); esmolol group), or landiolol (bolus of 0.125 mg/kg
      and then 0.04 mg x kg(-1) x min(-1); landiolol group) was started 5 min after the
      induction of anesthesia and was continued throughout the study. Tracheal
      intubation was performed 12 min after anesthesia induction. There were no
      differences in overall changes of mean arterial blood pressure among the three
      groups, whereas, at 1-5 min after tracheal intubation, heart rate increased in
      all groups but was significantly slower in the esmolol and landiolol groups than
      in the control group (P < 0.05). BIS was between 96 and 98 for all patients at
      baseline and decreased during the induction of anesthesia. There were no
      differences in BIS among the three groups before laryngoscopy (39 +/- 5, 39 +/-
      5, and 38 +/- 4 in the control, esmolol, and landiolol groups, respectively). BIS
      increased significantly in the control group (54 +/- 10; P < 0.05) 1 min after
      intubation, whereas it remained unchanged in the esmolol and landiolol groups (45
      +/- 10 and 41 +/- 6, respectively). In conclusion, the increase in both heart
      rate and BIS after tracheal intubation under 1 MAC sevoflurane anesthesia was
      suppressed by the concomitant administration of either esmolol or landiolol.

PMID- 15728063
TI  - The effect of venous pulsation on the forehead pulse oximeter wave form as a
      possible source of error in Spo2 calculation.
AB  - Reflective forehead pulse oximeter sensors have recently been introduced into
      clinical practice. They reportedly have the advantage of faster response times
      and immunity to the effects of vasoconstriction. Of concern are reports of signal
      instability and erroneously low Spo(2) values with some of these new sensors.
      During a study of the plethysmographic wave forms from various sites (finger,
      ear, and forehead) it was noted that in some cases the forehead wave form became
      unexpectedly complex in configuration. The plethysmographic signals from 25
      general anesthetic cases were obtained, which revealed the complex forehead wave
      form during 5 cases. We hypothesized that the complex wave form was attributable
      to an underlying venous signal. It was determined that the use of a pressure
      dressing over the sensor resulted in a return of a normal plethysmographic wave
      form. Further examination of the complex forehead wave form reveal a morphology
      consistent with a central venous trace with atrial, cuspidal, and venous waves.
      It is speculated that the presence of the venous signal is the source of the
      problems reported with the forehead sensors. It is believed that the venous wave
      form is a result of the method of attachment rather than the use of reflective
      plethysmographic sensors.

PMID- 15728062
TI  - Cutaneous heat loss with three surgical drapes, one impervious to moisture.
AB  - A new surgical drape that is impervious to moisture presumably reduces
      evaporative heat loss. We compared cutaneous heat loss and skin temperature in
      volunteers covered with this drape to two conventional surgical drapes (Large
      Surgical Drape and Medline Proxima). We calculated cutaneous heat loss and skin
      surface temperatures from 15 area-weighted thermal flux transducers in eight
      volunteers. In random order, each of the drapes was evaluated with dry
      transducers and moistened transducers (simulating wet skin). After a 20-min
      uncovered control period, volunteers were covered from the neck down for 40 min.
      Data were recorded continuously and averaged over 10 min. Results were similar
      for all three drapes for dry or moist conditions. Under dry conditions, baseline
      heat loss was 82 +/- 14 W and decreased 30% with a surgical drape (P < 0.001).
      Under moist conditions, baseline heat loss was 231 +/- 45 W and decreased 29%
      with a drape covering (P < 0.001). Moist skin increased heat loss 282% (P <
      0.001). There were no clinically important differences in skin temperature among
      the covers with dry or moist skin. Moist skin increased heat loss nearly three
      fold, but there were no differences among the drapes. We conclude that loss is
      comparable with impervious and conventional drapes with either moist or dry skin.

PMID- 15728064
TI  - Testing the reliability of a new ultrasonic cardiac output monitor, the USCOM, by
      using aortic flowprobes in anesthetized dogs.
AB  - We have used an animal model to test the reliability of a new portable continuous
      wave Doppler ultrasonic cardiac output monitor, the USCOM. In six anesthetized
      dogs, cardiac output was measured with a high-precision transit time ultrasonic
      flowprobe placed on the ascending aorta. The dogs' cardiac output was increased
      with a dopamine infusion (0-15 microg x kg(-1) x min(-1)). Simultaneous flowprobe
      and USCOM cardiac output measurements were made. Up to 64 pairs of readings were
      collected from each dog. Data were compared by using the Bland and Altman plot
      method and Lin's concordance correlation coefficient. A total of 319 sets of
      paired readings were collected. The mean (+/-sd) cardiac output was 2.62 +/- 1.04
      L/min, and readings ranged from 0.79 to 5.73 L/min. The mean bias between the 2
      sets of readings was -0.0l L/min, with limits of agreement (95% confidence
      intervals) of -0.34 to 0.31 L/min. This represents a +/-13% error. In five of six
      dogs, there was a high degree of concordance, or agreement, between the 2
      methods, with coefficients >0.9. The USCOM provided reliable measurements of
      cardiac output over a wide range of values. Clinical trials are needed to
      validate the device in humans.

PMID- 15728065
TI  - Preemptive analgesia at the crossroad.

PMID- 15728066
TI  - The efficacy of preemptive analgesia for acute postoperative pain management: a
      meta-analysis.
AB  - Whether preemptive analgesic interventions are more effective than conventional
      regimens in managing acute postoperative pain remains controversial. We
      systematically searched for randomized controlled trials that specifically
      compared preoperative analgesic interventions with similar postoperative
      analgesic interventions via the same route. The retrieved reports were stratified
      according to five types of analgesic interventions: epidural analgesia, local
      anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor
      antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic
      opioids. The primary outcome measures analyzed were the pain intensity scores,
      supplemental analgesic consumption, and time to first analgesic consumption.
      Sixty-six studies with data from 3261 patients were analyzed. Data were combined
      by using a fixed-effect model, and the effect size index (ES) used was the
      standardized mean difference. When the data from all three outcome measures were
      combined, the ES was most pronounced for preemptive administration of epidural
      analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic
      wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES,
      0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in
      consistent improvements in all three outcome variables, preemptive local
      anesthetic wound infiltration and NSAID administration improved analgesic
      consumption and time to first rescue analgesic request, but not postoperative
      pain scores. The least proof of efficacy was found in the case of systemic NMDA
      antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26
      to 0.07) administration, and the results remain equivocal.

PMID- 15728067
TI  - Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative
      pain.
AB  - Resiniferatoxin (RTX) is a vanilloid agonist with a unique spectrum of
      activities. Vanilloids bind to the transient receptor potential ion channel
      subtype 1, a nonselective cation ionophore important in the integration of
      different noxious signals. Vanilloid agonists selectively decrease sensitivity to
      noxious stimuli. In this study, we sought to determine whether perineural RTX
      prevents hyperalgesia in a model of incisional pain. In a rat model, RTX was
      administered percutaneously to the sciatic and saphenous nerves before the
      plantar incision. The withdrawal response to von Frey filaments, the struggle
      response to pressure on the paw, and pain scoring based on weight bearing were
      measured before RTX and at various intervals for 8 days after RTX. A percutaneous
      injection of RTX (0.0003%) to the sciatic (0.1 mL) and saphenous (0.05 mL) nerves
      completely prevented incisional hyperalgesia. Two hours after incision, the
      withdrawal threshold was 51 mN without and 456 mN with RTX (P < 0.0001). RTX also
      prevented the incision-induced decrease in struggle threshold and abolished the
      pain behavior associated with weight bearing. We conclude that RTX provides a
      type of neural blockade when postoperative pain is abolished and that nonpainful
      sensations and motor functions are preserved.

PMID- 15728068
TI  - Transdermal buprenorphine for treating nociceptive and neuropathic pain: four
      case studies.
AB  - The use of opioids for treating neuropathic pain is controversial, and some
      studies have indicated that neuropathic pain may be relatively insensitive to
      typical mu-opioid analgesics such as morphine. However, it is becoming clear that
      different opioids produce analgesia by affecting different pain pathways. We
      present two cases of neuropathic pain and two cases of nociceptive pain with a
      significant neuropathic component that were treated with transdermal
      buprenorphine. In each case, sufficient pain relief was obtained and no problems
      were encountered in switching from prior analgesic therapy with larger doses of
      other opioids.

PMID- 15728069
TI  - A retrospective comparison of costs for regional and general anesthesia
      techniques.
AB  - In this retrospective study, we compared the costs for three different regional
      anesthesia techniques with the costs of general anesthesia (GA). A total of 1587
      anesthesia cases which were performed for orthopedic and trauma patients over a 1
      yr period in a tertiary level, university hospital setting were analyzed. The
      anesthesia technique-related costs were determined calculating case-specific
      costs for personnel, supplies, and drugs. The techniques were compared on the
      basis of anesthesia costs and surgical procedure duration. As a result, we found
      that the costs per surgical minute largely depend on the surgical procedure
      duration. Based on the regression function, the cost advantage of spinal
      anesthesia over GA can be estimated to be 13% for a 50-min case, 9% for a 100-min
      case, and 5% for a 200-min case. The cost disadvantage of brachial plexus
      anesthesia over GA can be estimated to be 19% for a 50-min case, 8% in a 100-min
      case, and 1% for a 200-min case. We found no difference in costs between epidural
      and GA. We concluded that cost comparisons of anesthesia techniques largely
      depend on the surgical duration of the cases studied. Even in a teaching hospital
      setting, spinal anesthesia has economic advantages over GA. Especially for short
      cases, brachial plexus block is more expensive in this setting.

PMID- 15728070
TI  - The clinical effect of small oral clonidine doses on perioperative outcomes in
      patients undergoing abdominal hysterectomy.
AB  - We assessed the effect of small clonidine doses on anxiolysis, analgesia, and
      hemodynamic stability in patients undergoing abdominal hysterectomy. A total of
      61 patients, ASA status I-II, were randomly assigned to receive either oral
      clonidine 100 microg (n = 29) or placebo (n = 32) before surgery and 24 h after
      surgery. The use of clonidine resulted in anxiolysis and analgesia throughout the
      72 h after surgery, although the subjects who received clonidine were sleepier
      than the control group for the first 6 h after surgery. The number needed to
      treat was 3 (95% confidence interval [CI], 1.72-9.42) to prevent intense anxiety
      in patients with moderate to intense postoperative pain, compared with 40 (95%
      CI, 18.79-99.68) in the absence of pain or with mild pain. In the treated
      patients, 68% had an average heart rate less than 70 bpm during surgery, compared
      with 21.40% in the placebo group (number needed to treat, 2; 95% CI, 1.29-2.80).
      The clonidine patients required small ropivacaine doses during the surgery but
      not less morphine by patient-controlled analgesia. A clinically relevant
      anxiolytic effect was found in patients who received oral clonidine in the
      perioperative period, and this suggests that clonidine might be a useful
      therapeutic alternative to other preoperative sedatives.

PMID- 15728071
TI  - Using advanced simulation for recognition and correction of gaps in airway and
      breathing management skills in prehospital trauma care.
AB  - In this prospective study, we used two full-scale prehospital trauma scenarios
      (severe chest injury and severe head injury) and checklists of specific actions,
      reflecting essential actions for a safe treatment and successful outcome, were
      used to assess performance of postinternship physician graduates of the Advanced
      Trauma Life Support (ATLS) course. In the first 36 participants, simulated
      training followed basic training in airway and breathing management, whereas in
      the next 36 participants, 45 min of simulative training in airway management
      using the Air-Man simulator (Laerdal, Norway) were added before performing the
      study scenarios. The content of training was based on common mistakes performed
      by participants of the first group. After the change in training, the number of
      participants not performing cricoid pressure or not using medication during
      intubation decreased from 55% (20 of 36) to 8% (3 of 36) and from 42% (15 of 36)
      to 11% (4 of 36), respectively (P < 0.05). The number of participants not holding
      the tube properly before fixation decreased from 28% (10 of 36) to 0% (0 of 36)
      (P < 0.05). In the severe head trauma scenario, performed by 15 of 36
      participants in each group, the incidence of mistakes in the management of
      secondary airway or breathing problems after initial intubation decreased from
      60% (9 of 15) to 0% (0 of 15) (P < 0.05). The present study highlights problems
      in prehospital trauma management, as provided by the ATLS course. It seems that
      graduates may benefit from simulation-based airway and breathing training.
      However, clinical benefits from simulation-based training need to be evaluated.

PMID- 15728072
TI  - Attenuation of acute lung injury with propofol in endotoxemia.
AB  - Endotoxin causes acute lung injury (ALI) through many mediators of inflammatory
      and immune responses. Propofol is an antiinflammatory and immunosuppressive drug.
      We conducted this study to evaluate whether propofol attenuates ALI associated
      with endotoxemia. Thirty-two anesthetized rabbits were randomly divided into four
      groups (n = 8 each). ALI was induced by IV endotoxin 5 mg/kg over 30 min in 3
      groups. In 2 of the ALI groups, IV administration of propofol (2 or 5 mg/kg as a
      bolus followed by continuous infusion at 4 or 15 mg x kg(-1) x h(-1)) was started
      15 min before endotoxin. The other ALI group received soybean-oil emulsion. The
      nonlung injury control group received infusion of both vehicles. The lungs were
      mechanically ventilated with 40% oxygen for 6 h after endotoxin. Hemodynamics did
      not differ among groups. The large dose of propofol attenuated lung
      leukosequestration, pulmonary edema (as assessed by lung wet/dry weight ratio),
      and pulmonary hyperpermeability (as assessed by albumin levels in bronchoalveolar
      lavage fluid) and resulted in better oxygenation, lung mechanics, and
      histological change. The small dose of propofol failed to do so. Our findings
      suggest that a large dose of propofol successfully mitigates physiological,
      biochemical, and histological deterioration in ALI in endotoxemia.

PMID- 15728073
TI  - The influence of trauma and ischemia on carbohydrate metabolites monitored in
      hamster flap tissue.
AB  - To monitor hypoperfusion of the peripheral tissues in critical illness caused by
      injury, we measured the concentrations of glucose, pyruvate, and lactate in
      traumatized and ischemic hamster flap tissue with the use of microdialysis. The
      interruption of the anatomic blood supply led to a drastic decrease in
      microvascular blood flow (laser Doppler flowmetry) and partial tissue oxygen
      tension (dye fluorescence quenching technique) in the ischemic part of the flap
      (both P < 0.01). In the traumatized area, blood flow, oxygen tension, and
      pyruvate were similar to the healthy control tissue throughout the experiments,
      whereas pyruvate was reduced in the ischemic tissue (P < 0.05 versus baseline and
      other tissues). Lactate was increased in both parts of the flap (P < 0.01 versus
      baseline and other groups for ischemic, not significant for traumatized). The
      sensitivity to detect ischemic hypoxia was 62% for lactate and 93% for
      lactate/pyruvate ratio (L/P) (P < 0.01). The specificity to discern ischemia
      related from trauma-related changes was 71% for lactate and 70% for L/P (not
      significant). Our results suggest that L/P is more accurate than lactate for
      monitoring ischemia-related hypoxia after trauma. However, the rate of increased
      values originating from normally perfused but traumatized tissue was high for
      both markers.

PMID- 15728074
TI  - Sepsis stage dependently and differentially attenuates the effects of
      nondepolarizing neuromuscular blockers on the rat diaphragm in vitro.
AB  - We investigated the effects of early and late sepsis on the actions of
      nondepolarizing neuromuscular blockers by using a rat sepsis model induced by
      cecal ligation and puncture. Isometric twitch tensions of nerve-hemidiaphragm
      preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1
      Hz were evaluated. Rocuronium, pancuronium, and d-tubocurarine dose-dependently
      decreased the twitch tensions of the nonseptic, early septic, and late septic
      diaphragms (P < 0.01 each by analysis of variance [ANOVA]). Late sepsis shifted
      the concentration-twitch tension curves rightward from those of nonsepsis to
      larger degrees than did early sepsis, as indicated by increases in 50% inhibitory
      concentration (IC(50)) values (P < 0.01 each by ANOVA and P < 0.01 or 0.05 by the
      Scheffe F test). The standardized rightward shifts in early and late sepsis were
      largest for pancuronium, second largest for rocuronium, and smallest for d
      tubocurarine (5.741, 2.979, and 1.660 times in late sepsis, respectively; P <
      0.01 each by ANOVA and the Scheffe F test). Sepsis-induced increases in IC(50)
      values did not accompany the decreases in slopes. The results indicate that
      sepsis induces hyposensitivities to nondepolarizing neuromuscular blockers, the
      degree of which depends on the stage of sepsis and on the kind of neuromuscular
      blocker.

PMID- 15728076
TI  - The effects of propofol or sevoflurane on the estimated cerebral perfusion
      pressure and zero flow pressure.
AB  - The zero flow pressure (ZFP) is the pressure at which blood flow ceases through a
      vascular bed. Using transcranial Doppler ultrasonography, we investigated the
      effects of propofol or sevoflurane on the estimated cerebral perfusion pressure
      (eCPP) and ZFP in the cerebral circulation. Twenty-three healthy patients
      undergoing nonneurosurgical procedures under general anesthesia were studied.
      After induction of anesthesia using propofol, the anesthesia was maintained with
      either propofol infusion (n = 13) or sevoflurane (n = 10). Middle cerebral artery
      flow velocity, noninvasive arterial blood pressure, and end-tidal carbon dioxide
      partial pressure were recorded awake as a baseline, and during steady-state
      anesthesia at normocapnia (baseline end-tidal carbon dioxide partial pressure)
      and hypocapnia (1 kPa below baseline). The eCPP and ZFP were calculated using an
      established formula. The mean arterial blood pressure decreased in both groups.
      The eCPP decreased significantly in the propofol group (median, from 58 to 41 mm
      Hg) but not in the sevoflurane group (from 60 to 62 mm Hg). Correspondingly, ZFP
      increased significantly in the propofol group (from 25 to 33 mm Hg) and it
      decreased significantly in the sevoflurane group (from 27 to 7 mm Hg). Hypocapnia
      did not change eCPP or ZFP in the propofol group, but it significantly decreased
      eCPP and increased ZFP in the sevoflurane group.

PMID- 15728075
TI  - A single local application of recombinant human basic fibroblast growth factor
      accelerates initial angiogenesis during wound healing in rabbit ear chamber.
AB  - Local angiogenic therapy with recombinant human basic fibroblast growth factor
      (rhbFGF) has been used to promote wound healing. To obtain useful information for
      the development of optimal angiogenic therapy, we chronologically evaluated the
      effects of a single local application of rhbFGF on angiogenesis in a rabbit ear
      chamber model of wound healing by observing the subcutaneous vessel bed
      intravitally. New vessel formation during wound healing was macroscopically and
      microscopically evaluated for 5 wk. Each rabbit ear chamber received a single
      dose of 6 microg rhbFGF (treatment B1: n = 13), 18 microg rhbFGF (treatment B2: n
      = 16), or physiological saline as control (n = 13). At 1 wk the newly
      vascularized area was significantly larger in groups B1 and B2 than in control.
      At 2 wk, the vascularized areas in groups B1, B2, and control were similar. At 5
      wk, the percentage of rabbits with complete vascularization was significantly
      larger in group B1 than in control. Capillary density at 5 wk was similar among
      the three groups. These results suggest that locally applied rhbFGF accelerated
      angiogenesis during early wound healing in rabbits; however, this effect was
      transient and no increase in capillary density occurred at the completion of
      vascularization.

PMID- 15728077
TI  - The role of nitric oxide synthase inhibition in the adverse effects of etomidate
      in the setting of focal cerebral ischemia in rats.
AB  - We evaluated the effect of N(G)-nitro-L-arginine-methyl-ester (l-NAME, a nitric
      oxide synthase [NOS] inhibitor) and L-arginine (nitric oxide substrate) on
      cerebral mitochondrial dysfunction (hereafter referred to as "injury") after
      temporary middle cerebral artery occlusion (MCAo) during halothane or etomidate
      anesthesia in spontaneously hypertensive rats. Sixty minutes before MCAo, rats
      were randomized to 1 of 5 regimens (n = 8 per group): h/control, 1.2 minimum
      alveolar anesthetic concentration of halothane; h/L-NAME, 1.2 minimum alveolar
      anesthetic concentration of halothane and L-NAME (30 mg/kg); etomidate, an
      electroencephalographic (EEG) burst suppression dose of etomidate; e/L-NAME, an
      EEG burst suppression dose of etomidate and L-NAME (30 mg/kg); or e/L-NAME/arg,
      an EEG burst suppression dose of etomidate, L-NAME (30 mg/kg), and L-arginine
      (bolus of 300 mg/kg with an infusion at 35 mg x kg(-1) x min(-1)). After 180 min
      of MCAo and 120 min of reperfusion, volume of injury was determined using 2,3,5
      triphenytetrazolium stain. Injury volume (mm(3), mean +/- sd) was larger in the
      etomidate group (153 +/- 17) than the halothane anesthetized h/control group (93
      +/- 16) (P < 0.05) but did not differ between the e/L-NAME (162 +/- 17) and h/L
      NAME groups (155 +/- 26). Injury volume in the e/L-NAME/arg group (88 +/- 15) was
      not different from the h/control group (93 +/- 16) and was less than that in
      either the etomidate or the e/L-NAME groups (P < 0.05). The data reproduce our
      previous observation that, relative to a halothane-anesthetized control state,
      etomidate has an adverse effect on ischemic injury in the setting of temporary
      focal cerebral ischemia. Prior inhibition of NOS with L-NAME resulted in no
      difference in the volume of injury between groups receiving etomidate or
      halothane (162 +/- 17 versus 155 +/- 26). Administration of a large dose of L
      arginine prevented the adverse effect of etomidate. The data were obtained after
      only 2 h of reperfusion and therefore cannot be construed as representative of
      final neurologic outcome. They nonetheless suggest that etomidate produces an
      adverse effect on mitochondrial function early in the course of focal cerebral
      ischemia, in part, by inhibition of NOS.

PMID- 15728078
TI  - An evaluation of white matter injury after spinal cord ischemia in rats: a
      comparison with gray matter injury.
AB  - We quantitatively assessed both gray and white matter injury after spinal cord
      ischemia in rats, and the relationship between the magnitude of gray and white
      matter injury was determined. Twenty-five male rats were anesthetized with
      isoflurane, and spinal cord ischemia (SCI) was induced by balloon intraaortic
      occlusion combined with hypotension. The animals were randomly allocated to one
      of the following three groups: animals with SCI for 12 min (SCI-12; n = 8), 15
      min (SCI-15; n = 9), or those with sham operation (n = 8). Twenty-four hours
      after reperfusion, hindlimb motor function was assessed using the Basso-Beattie
      Bresnahan scale scoring. Gray matter damage was assessed on the basis of the
      number of normal neurons in the ventral horn. White matter damage was assessed on
      the basis of the extent of vacuolation and amyloid precursor protein
      immunoreactivity in the ventral and ventrolateral white matter. There were
      significantly less normal neurons in the SCI-15 group compared with those in the
      SCI-12 and sham groups (P < 0.05). There was a significant positive correlation
      between the Basso-Beattie-Bresnahan scores and the number of normal neurons. The
      percentages of vacuolation areas in the SCI-15 group were significantly larger
      compared with those in the SCI-12 and sham groups (30% +/- 10% versus 9% +/- 7%,
      0% +/- 0%, P < 0.05). Immunohistochemical analysis revealed increased amyloid
      precursor protein immunoreactivity in the swollen axons, especially in the SCI-15
      group. There was a significant negative correlation between the number of normal
      neurons and percentages of vacuolation areas. These results indicate that both
      gray and white matter were injured after SCI in rats and the degree of white
      mater injury was correlated with the severity of gray matter injury after a
      relatively short recovery period.

PMID- 15728079
TI  - Cardiac arrest during neuraxial anesthesia: frequency and predisposing factors
      associated with survival.
AB  - The frequency and predisposing factors associated with cardiac arrest during
      neuraxial anesthesia remain undefined, and the survival outcome data are
      contradictory. In this retrospective study, we evaluated the frequency of cardiac
      arrest, as well as the association of preexisting medical conditions and
      periarrest events with survival after cardiac arrest during neuraxial anesthesia
      between 1983 and 2002. To assess whether survival after cardiac arrest differs
      for patients who arrest during neuraxial versus general anesthesia, data were
      also obtained for patients who experienced cardiac arrest under general
      anesthesia during similar surgical procedures during the same time interval. Over
      the 20-yr study period at the Mayo Clinic, there were 26 cardiac arrests during
      neuraxial blockade and 29 during general anesthesia. The overall frequency of
      cardiac arrest during neuraxial anesthesia for 1988 to 2002 was 1.8 per 10,000
      patients, with more arrests in patients receiving spinal versus epidural
      anesthesia (2.9 versus 0.9 per 10,000; P = 0.041). In 14 (54%) of the 26 patients
      who arrested during a neuraxial technique, the anesthetic contributed directly to
      the arrest (high sympathectomy or respiratory depression after sedative
      administration), whereas in 12 (46%) patients, the arrest was associated with a
      specific surgical event (cementing of joint components, spermatic cord
      manipulation, reaming of the femur, and rupture of amniotic membranes). Patients
      who arrested during general anesthesia had a higher ASA classification than those
      who arrested during a neuraxial block (P = 0.031). Hospital survival was
      significantly improved for patients who arrested during neuraxial anesthesia
      versus general anesthesia (65% vs 31%; P = 0.013). The association of improved
      survival with neuraxial anesthesia remained statistically significant after
      adjusting for all patient/procedural characteristics, with the exception of ASA
      classification and emergency procedures. We conclude that a cardiac arrest during
      neuraxial anesthesia is associated with an equal or better likelihood of survival
      than a cardiac arrest during general anesthesia.

PMID- 15728080
TI  - Adding clonidine to the induction bolus and postoperative infusion during
      continuous femoral nerve block delays recovery of motor function after total knee
      arthroplasty.
AB  - We evaluated the effects of adding clonidine for continuous peripheral nerve
      infusions. Sixty patients undergoing total knee arthroplasty under combined
      single-injection sciatic block and continuous femoral infusion were randomly
      allocated to three groups: block induction with 0.75% ropivacaine followed by
      0.2% ropivacaine (group control; n = 20); block induction with 0.75% ropivacaine
      and 1 microg/kg clonidine followed by 0.2% ropivacaine (group cloni-bolus; n =
      20), and block induction with 0.75% ropivacaine and 1 microg/kg clonidine
      followed by 0.2% ropivacaine with 1 microg/mL clonidine (group cloni-infusion; n
      = 20). After surgery, continuous femoral infusion was provided with a patient
      controlled infusion pump (basal infusion rate, 6 mL/h; incremental dose, 2 mL;
      lockout time, 15 min). The median (range) onset time of surgical block was 15 min
      (5-30 min) in group control, 10 min (5-35 min) in group cloni-bolus, and 10 min
      (5-30 min) in group cloni-infusion (P = 0.07). No differences were reported among
      groups in the degree of pain measured with the visual analog scale. The total
      consumption of local anesthetic solution after a 24-h infusion was 170 mL (144
      220 mL) in group control, 169 mL (144-260 mL) in group cloni-bolus, and 164 mL
      (144-248 mL) in group cloni-infusion (P = 0.51); after the second day of
      infusion, total consumption was 168 mL (144-200 mL) in group control, 156 mL (144
      288 mL) in group cloni-bolus, and 150 mL (144-210 mL) in group cloni-infusion (P
      = 0.48). Hemodynamic profiles and sedation were similar in the three groups.
      Motor function impairment after 48 h of infusion was observed in 27% of cloni
      infusion patients but in only 6% of both the control and cloni-bolus groups (P =
      0.05). We conclude that adding clonidine 1 microg/mL to local anesthetic for
      continuous femoral nerve block does not improve the quality of pain relief but
      has the potential for delaying recovery of motor function.

PMID- 15728081
TI  - Intravenous but not perineural clonidine prolongs postoperative analgesia after
      psoas compartment block with 0.5% levobupivacaine for hip fracture surgery.
AB  - We evaluated the systemic and local effects of clonidine as an analgesic adjunct
      to psoas compartment block (PCB) with levobupivacaine. In a randomized,
      prospective, double-blind trial, 36 patients requiring hip fracture surgery
      received PCB and general anesthesia. Patients were randomized into three groups.
      Each patient received PCB with 0.4 mL/kg of levobupivacaine 0.5%. The control
      group (group L) received IV saline, the systemic clonidine group (group IC)
      received IV clonidine 1 mug/kg, and the peripheral clonidine group (group C)
      received IV saline and PCB with clonidine 1 microg/kg. The interval from time of
      completion of block injection to first supplementary analgesic administration was
      longer in group IC compared with group L (mean +/- sd, 13.4 +/- 6.1 versus 7.3 +/
      3.6 h; P = 0.03). There was no difference between group C and group L (10.3 +/-
      5.9 versus 7.3 +/- 3.6 h; P > 0.05). The groups were similar in terms of 24 h
      cumulative morphine and acetaminophen consumption. There were no significant
      differences among groups regarding postoperative adverse effects (bradycardia,
      hypotension, sedation, and nausea). We conclude that IV but not perineural
      clonidine (1 microg/kg) prolongs analgesia after PCB without increasing the
      incidence of adverse effects.

PMID- 15728082
TI  - Postdural puncture headache with abdominal pain and diarrhea.
AB  - Dural puncture or a rent in the dura with prolonged cerebrospinal fluid leakage
      may cause noninfectious arachnoiditis and may be associated with urinary and
      fecal incontinence. Visceral dysfunction is common for patients with
      noninfectious arachnoiditis of the lumbosacral nerve roots after dural puncture.
      We report a case of postdural puncture headache associated with abdominal pain
      and diarrhea. An epidural blood patch was performed, and all symptoms resolved
      after 5 days. After exclusion of organic and psychological disorders, this
      treatment might be considered for patients who are experiencing abdominal pain
      and diarrhea after dural puncture.

PMID- 15728083
TI  - Epidural hematoma unrelated to combined spinal-epidural anesthesia in a patient
      with ankylosing spondylitis receiving aspirin after total hip replacement.
AB  - Although rare, major complications after spinal and epidural anesthesia do occur.
      The safety of spinal and epidural anesthesia has been well established. This is a
      report of an epidural hematoma in a patient with ankylosing spondylitis who
      received aspirin for thromboprophylaxis after total hip replacement that was
      unrelated to the combined spinal-epidural anesthetic. Most epidural hematomas are
      spontaneous and idiopathic.

PMID- 15728084
TI  - Capnogram shape in obstructive lung disease.
AB  - Small, preliminary studies have suggested that capnograms of obstructive lung
      disease (OD) exhibit a characteristic shape and that this shape may be correlated
      to changes in forced expiratory volume in 1 s (FEV(1)). We evaluated the
      association between capnograms and spirometry from subjects with OD with normal
      and restrictive lung disease (RD) subjects. The study was conducted in a
      prospective, nonrandomized manner using a convenience sample of 262 subjects
      presenting to a pulmonary function laboratory. Capnograms were recorded before
      pulmonary function testing. Subjects with OD had capnograms that were
      significantly different from normal and RD subjects. These differences were
      progressive, increasing with disease severity. The average take-off angle of the
      ascending phase for severe OD was 7.2 degrees less (95% confidence interval [CI]:
      4.0, 10.4) than for normals. The average alveolar plateau elevation angle was 0.8
      degrees more (95% CI: 0.14, 1.4) for moderate OD than for normals, whereas the
      average elevation angle was 3.6 degrees more (95% CI: 2.9, 4.3) for severe OD
      than for normals. Differences between OD capnograms and normal and RD capnograms,
      correlating to changes in FEV(1), were sufficiently large enough to suggest that
      the capnogram could be used to discriminate between OD and normal.

PMID- 15728085
TI  - Peak airway pressure increase is a late warning sign of partial endotracheal tube
      obstruction whereas change in expiratory flow is an early warning sign.
AB  - If peak inspiratory airway pressure (Ppeak) is used to monitor airway patency,
      progressive obstruction of the endotracheal tube (ETT) resulting from secretions
      can go undetected for a prolonged period. The reason is that any increase in
      Ppeak depends not only on the degree of narrowing but also on the inspiratory
      flow () rate. Although the impact of narrowing on low inspiratory is small, its
      decelerating effect on the high expiratory is pronounced and, hence, easily
      detectable. Dividing the volume-flow curve of a passive expiration into five
      consecutive segments (slices) and calculating the time constants (tau(Epsilon))
      of these slices allows for analyzing whether and how expiratory is impeded by a
      partial obstruction. In nine piglets, during volume-controlled ventilation, three
      grades of ETT obstruction were created with an external clamp. In all animals the
      tau(E) increased with ETT obstruction (mean for the first slice: 550 ms with
      unobstructed ETT; grade 1: 661; grade 2: 877; and grade 3: 1563 ms, respectively)
      and this increase was significant with grade 2 and 3 obstruction. Ppeak, by
      contrast, did not increase significantly (base: 13, grade 1: 14, grade 2: 15 cm
      H(2)O) until the most severe (grade 3: 20 cm H(2)O) obstruction was created. We
      conclude that partial obstruction of the ETT can be reliably monitored with the
      expiratory V signal and has the potential of monitoring ETT narrowing in
      ventilator-dependent patients independent of the inspiratory pattern applied.

PMID- 15728086
TI  - The anesthetic management of a case of tracheal necrosis.
AB  - A 63-yr-old female patient developed a tracheal necrosis after esophageal
      resection with gastric interposition. We report the anesthetic management of this
      patient undergoing tracheal repair focusing on an original airway management and
      ventilation strategy.

PMID- 15728087
TI  - Time to dispose of nondisposable LMAs.

PMID- 15728089
TI  - Exhaled CO after surgery: a consequence of postoperative narcotics?

PMID- 15728090
TI  - Extremely prolonged unilateral block (20 hours) with spinal ropivacaine used for
      cervical cerclage placement.

PMID- 15728092
TI  - An alternative and simple technique of guidewire retrieval in a failed Seldinger
      technique.

PMID- 15728093
TI  - Rhabdomyolysis associated with Crohn's disease, probably mediated by myositis.

PMID- 15728094
TI  - The importance of a laryngoscopy strategy and optimal conditions in emergency
      intubation.

PMID- 15728095
TI  - OT light camera as an intravenous cannulation assist device.

PMID- 15728097
TI  - A new friendly approach to pediatric inhaled induction.

PMID- 15728099
TI  - Impact of volume loading on systolic mitral annular velocity (Sm) by tissue
      Doppler imaging.

PMID- 15728101
TI  - Use of the CobraPLA for percutaneous cricothyroidotomy and tracheostomy.

PMID- 15728102
TI  - Tourniquet palsy or residual block?

PMID- 15728104
TI  - Pain reduction by IV butorphanol prior to propofol.

PMID- 15728105
TI  - Bispectral index and propofol induction: beware of inappropriate conclusions.

PMID- 15728107
TI  - Mortality from lung and kidney disease in a cohort of North American industrial
      sand workers: an update.
AB  - BACKGROUND: A previously published cohort study of some 2670 employees of the
      North American sand industry, followed through 1994, provided strong evidence of
      a causal relationship between quartz exposure and death from both silicosis and
      lung cancer, after allowance for cigarette smoking and in the absence of known
      occupational carcinogens. Unexpectedly, a significant excess mortality from
      chronic non-malignant renal disease [observed 16; expected 7.6; standardized
      mortality ratio (SMR) 212] was also found, whereas deaths from renal cancer at
      this stage were close to expectation (observed 6; expected 5.2). OBJECTIVES: Our
      primary aim was to discover whether death from chronic renal disease was related
      to the estimated intensity of crystalline silica exposure. A further aim was to
      determine whether or not our previous estimates of lung cancer and silicosis risk
      were confirmed by mortality in the cohort 6 years later. METHODS: With help from
      the US National Death Index, surviving members of the cohort, with the exception
      of employees of a small plant in Canada, were traced through 2000. The cause of
      death was determined for all who had died, for comparison against National and
      State mortality rates. Nested case-referent analyses were then undertaken, as
      previously, of deaths from lung cancer and silicosis, plus end-stage renal
      disease and kidney cancer, in relation to quantitative re-estimates of quartz
      exposure. RESULTS: The total number of deaths through 1994 was 990; there were
      231 additional deaths during the period 1995-2000. The SMRs were significantly
      higher in the later than the earlier period, mainly due to a relative increase in
      heart disease and external causes. The updated odds ratios for lung cancer and
      silicosis were almost identical to those published previously, with lung cancer
      risk again related to average silica concentration and cumulative exposure, but
      not to length of employment. In contrast, risks of neither end-stage renal
      disease nor renal cancer were related to cumulative exposure, although now based
      on 19 cases (SMR 239), and 10 cases (SMR 202), respectively, in fact, opposite
      trends were apparent for both diseases. However, because of the small numbers
      there was only limited power to assess the statistical significance of these
      trends or of any separate relationship with the duration or intensity of
      exposure. CONCLUSIONS: Our findings support a causal relationship between lung
      cancer and quartz exposure after allowance for cigarette smoking, in the absence
      of other known carcinogens, but failed to find similar evidence to explain the
      excess mortality from either chronic renal disease or kidney cancer.

PMID- 15728108
TI  - Skin rash and good performance status predict improved survival with gefitinib in
      patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: Gefitinib (Iressa) is active as a single agent in the treatment of
      select patients with recurrent non-small cell lung cancer (NSCLC). The clinical
      characteristics of patients treated with gefitinib on an Expanded Access Program
      (EAP) at our institution identified predictive variables associated with better
      outcome. PATIENTS AND METHODS: Patients (n=199) with advanced NSCLC were treated
      with gefitinib (250 mg) upon progression with chemotherapy. Baseline patient
      characteristics were: median age, 69 years; males, 57%; adenocarcinoma, 56%.
      RESULTS: Partial responses were noted in two patients (1%) and disease
      stabilization in 66 (35%) patients. The median survival (MS) was 5.9 months [95%
      confidence interval (CI) 4.1-7.1] and median time to progression was 3 months
      (95% CI 2.0-3.0). The predictive factors analyzed were gender, skin rash,
      diarrhea, tumor histology and performance status (PS). Patients who developed
      skin rash (any grade) had MS of 10.8 months versus 4.0 months for those without
      rash (P <0.0001, log rank test). Patients with PS 0, 1 and 2 had MS of 8.4, 6.2
      and 2.8 months, respectively (P <0.0002). The other factors did not impact
      survival. CONCLUSIONS: Occurrence of skin rash and baseline PS of 0/1 were
      associated with improved survival with gefitinib for recurrent NSCLC patients at
      our institution.

PMID- 15728109
TI  - mTOR-targeted therapy of cancer with rapamycin derivatives.
AB  - Rapamycin and its derivatives (CCI-779, RAD001 and AP23576) are immunosuppressor
      macrolides that block mTOR (mammalian target of rapamycin) functions and yield
      antiproliferative activity in a variety of malignancies. Molecular
      characterization of upstream and downstream mTOR signaling pathways is thought to
      allow a better selection of rapamycin-sensitive tumours. For instance, a loss of
      PTEN functions results in Akt phosphorylation, cell growth and proliferation;
      circumstances that can be blocked using rapamycin derivatives. From recent
      studies, rapamycin derivatives appear to display a safe toxicity profile with
      skin rashes and mucositis being prominent and dose-limiting. Sporadic activity
      with no evidence of dose-effect relationship has been reported. Evidence suggests
      that rapamycin derivatives could induce G1-S cell cycle delay and eventually
      apoptosis depending on inner cellular characteristics of tumour cells. Surrogate
      molecular markers that could be used to monitor biological effects of rapamycin
      derivatives and narrow down biologically active doses in patients, such as the
      phosphorylation of P70S6K or expression of cyclin D1 and caspase 3, are currently
      evaluated. Since apoptosis induced by rapamycin is blocked by BCL-2, strategies
      aimed at detecting human tumours that express BCL-2 and other anti-apoptotic
      proteins might allow identification of rapamycin-resistant tumours. Finally, we
      discuss current and future placements of rapamycin derivatives and related
      translational research into novel therapeutic strategies against cancer.

PMID- 15728110
TI  - GMAP: a genomic mapping and alignment program for mRNA and EST sequences.
AB  - MOTIVATION: We introduce GMAP, a standalone program for mapping and aligning cDNA
      sequences to a genome. The program maps and aligns a single sequence with minimal
      startup time and memory requirements, and provides fast batch processing of large
      sequence sets. The program generates accurate gene structures, even in the
      presence of substantial polymorphisms and sequence errors, without using
      probabilistic splice site models. Methodology underlying the program includes a
      minimal sampling strategy for genomic mapping, oligomer chaining for approximate
      alignment, sandwich DP for splice site detection, and microexon identification
      with statistical significance testing. RESULTS: On a set of human messenger RNAs
      with random mutations at a 1 and 3% rate, GMAP identified all splice sites
      accurately in over 99.3% of the sequences, which was one-tenth the error rate of
      existing programs. On a large set of human expressed sequence tags, GMAP provided
      higher-quality alignments more often than blat did. On a set of Arabidopsis
      cDNAs, GMAP performed comparably with GeneSeqer. In these experiments, GMAP
      demonstrated a several-fold increase in speed over existing programs.
      AVAILABILITY: Source code for gmap and associated programs is available at
      http://www.gene.com/share/gmap SUPPLEMENTARY INFORMATION:
      http://www.gene.com/share/gmap.

PMID- 15728111
TI  - Mapping genome-genome epistasis: a high-dimensional model.
AB  - MOTIVATION: The proper development of any organ or tissue requires the
      coordinated expression of its underlying genes that can be located on different
      genomes present in an organism. For instance, each step in the development of
      seed for a higher plant is the consequence of gene interactions from the
      maternal, embryo and endosperm genomes. RESULTS: We present a multivariate
      statistical model for mapping quantitative trait loci (QTL) by incorporating two
      important aspects of seed development in plants-QTL interactions derived from
      different genomes, the maternal, embryo and endosperm, and genetic correlations
      among phenotypic traits expressed in different genome-specific tissues. This
      model, which has a high dimensionality, is constructed within the maximum
      likelihood context based on a finite mixture model. The implementation of the
      expectation-maximization algorithm allows for the efficient estimation of QTL
      positions, their action and interaction effects and pleiotropic effects. The
      application of this high-dimensional model to a real rice dataset has validated
      its usefulness. CONCLUSIONS: Our model was derived for self-pollinated plants,
      but it can be extended to cross-pollinated plants and to animals. With the
      burgeoning of genetic and genomic data, this high-dimensional model will have
      many implications for agricultural and evolutionary genetic research.
      AVAILABILITY: A package of software will be provided from the corresponding
      author upon request.

PMID- 15728112
TI  - Background correction for cDNA microarray images using the TV+L1 model.
AB  - MOTIVATION: Background correction is an important preprocess in cDNA microarray
      data analysis. A variety of methods have been used for this purpose. However,
      many kinds of backgrounds, especially inhomogeneous ones, cannot be estimated
      correctly using any of the existing methods. In this paper, we propose the use of
      the TV+L1 model, which minimizes the total variation (TV) of the image subject to
      an L1-fidelity term, to correct background bias. We demonstrate its advantages
      over the existing methods by both analytically discussing its properties and
      numerically comparing it with morphological opening. RESULTS: Experimental
      results on both synthetic data and real microarray images demonstrate that the
      TV+L1 model gives the restored intensity that is closer to the true data than
      morphological opening. As a result, this method can serve an important role in
      the preprocessing of cDNA microarray data.

PMID- 15728113
TI  - An evolution based classifier for prediction of protein interfaces without using
      protein structures.
AB  - MOTIVATION: The number of available protein structures still lags far behind the
      number of known protein sequences. This makes it important to predict which
      residues participate in protein-protein interactions using only sequence
      information. Few studies have tackled this problem until now. RESULTS: We applied
      support vector machines to sequences in order to generate a classification of all
      protein residues into those that are part of a protein interface and those that
      are not. For the first time evolutionary information was used as one of the
      attributes and this inclusion of evolutionary importance rankings improves the
      classification. Leave-one-out cross-validation experiments show that prediction
      accuracy reaches 64%.

PMID- 15728114
TI  - Selective integration of multiple biological data for supervised network
      inference.
AB  - MOTIVATION: Inferring networks of proteins from biological data is a central
      issue of computational biology. Most network inference methods, including
      Bayesian networks, take unsupervised approaches in which the network is totally
      unknown in the beginning, and all the edges have to be predicted. A more
      realistic supervised framework, proposed recently, assumes that a substantial
      part of the network is known. We propose a new kernel-based method for supervised
      graph inference based on multiple types of biological datasets such as gene
      expression, phylogenetic profiles and amino acid sequences. Notably, our method
      assigns a weight to each type of dataset and thereby selects informative ones.
      Data selection is useful for reducing data collection costs. For example, when a
      similar network inference problem must be solved for other organisms, the dataset
      excluded by our algorithm need not be collected. RESULTS: First, we formulate
      supervised network inference as a kernel matrix completion problem, where the
      inference of edges boils down to estimation of missing entries of a kernel
      matrix. Then, an expectation-maximization algorithm is proposed to simultaneously
      infer the missing entries of the kernel matrix and the weights of multiple
      datasets. By introducing the weights, we can integrate multiple datasets
      selectively and thereby exclude irrelevant and noisy datasets. Our approach is
      favorably tested in two biological networks: a metabolic network and a protein
      interaction network. AVAILABILITY: Software is available on request.

PMID- 15728115
TI  - MaSTerClass: a case-based reasoning system for the classification of biomedical
      terms.
AB  - MOTIVATION: The sheer volume of textually described biomedical knowledge exerts
      the need for natural language processing (NLP) applications in order to allow
      flexible and efficient access to relevant information. Specialized semantic
      networks (such as biomedical ontologies, terminologies or semantic lexicons) can
      significantly enhance these applications by supplying the necessary
      terminological information in a machine-readable form. With the explosive growth
      of bio-literature, new terms (representing newly identified concepts or
      variations of the existing terms) may not be explicitly described within the
      network and hence cannot be fully exploited by NLP applications. Linguistic and
      statistical clues can be used to extract many new terms from free text. The
      extracted terms still need to be correctly positioned relative to other terms in
      the network. Classification as a means of semantic typing represents the first
      step in updating a semantic network with new terms. RESULTS: The MaSTerClass
      system implements the case-based reasoning methodology for the classification of
      biomedical terms.

PMID- 15728116
TI  - Real spherical harmonic expansion coefficients as 3D shape descriptors for
      protein binding pocket and ligand comparisons.
AB  - MOTIVATION: An increasing number of protein structures are being determined for
      which no biochemical characterization is available. The analysis of protein
      structure and function assignment is becoming an unexpected challenge and a major
      bottleneck towards the goal of well-annotated genomes. As shape plays a crucial
      role in biomolecular recognition and function, the examination and development of
      shape description and comparison techniques is likely to be of prime importance
      for understanding protein structure-function relationships. RESULTS: A novel
      technique is presented for the comparison of protein binding pockets. The method
      uses the coefficients of a real spherical harmonics expansion to describe the
      shape of a protein's binding pocket. Shape similarity is computed as the L2
      distance in coefficient space. Such comparisons in several thousands per second
      can be carried out on a standard linux PC. Other properties such as the
      electrostatic potential fit seamlessly into the same framework. The method can
      also be used directly for describing the shape of proteins and other molecules.
      AVAILABILITY: A limited version of the software for the real spherical harmonics
      expansion of a set of points in PDB format is freely available upon request from
      the authors. Binding pocket comparisons and ligand prediction will be made
      available through the protein structure annotation pipeline Profunc (written by
      Roman Laskowski) which will be accessible from the EBI website shortly.

PMID- 15728117
TI  - A Gibbs sampler for identification of symmetrically structured, spaced DNA motifs
      with improved estimation of the signal length.
AB  - MOTIVATION: Transcription regulatory protein factors often bind DNA as homo
      dimers or hetero-dimers. Thus they recognize structured DNA motifs that are
      inverted or direct repeats or spaced motif pairs. However, these motifs are often
      difficult to identify owing to their high divergence. The motif structure
      included explicitly into the motif recognition algorithm improves recognition
      efficiency for highly divergent motifs as well as estimation of motif geometric
      parameters. RESULT: We present a modification of the Gibbs sampling motif
      extraction algorithm, SeSiMCMC (Sequence Similarities by Markov Chain Monte
      Carlo), which finds structured motifs of these types, as well as non-structured
      motifs, in a set of unaligned DNA sequences. It employs improved estimators of
      motif and spacer lengths. The probability that a sequence does not contain any
      motif is accounted for in a rigorous Bayesian manner. We have applied the
      algorithm to a set of upstream regions of genes from two Escherichia coli
      regulons involved in respiration. We have demonstrated that accounting for a
      symmetric motif structure allows the algorithm to identify weak motifs more
      accurately. In the examples studied, ArcA binding sites were demonstrated to have
      the structure of a direct spaced repeat, whereas NarP binding sites exhibited the
      palindromic structure. AVAILABILITY: The WWW interface of the program, its
      FreeBSD (4.0) and Windows 32 console executables are available at
      http://bioinform.genetika.ru/SeSiMCMC

PMID- 15728118
TI  - A word-oriented approach to alignment validation.
AB  - MOTIVATION: Multiple sequence alignment at the level of whole proteomes requires
      a high degree of automation, precluding the use of traditional validation methods
      such as manual curation. Since evolutionary models are too general to describe
      the history of each residue in a protein family, there is no single
      algorithm/model combination that can yield a biologically or evolutionarily
      optimal alignment. We propose a 'shotgun' strategy where many different
      algorithms are used to align the same family, and the best of these alignments is
      then chosen with a reliable objective function. We present WOOF, a novel 'word
      oriented' objective function that relies on the identification and scoring of
      conserved amino acid patterns (words) between pairs of sequences. RESULTS: Tests
      on a subset of reference protein alignments from BAliBASE showed that WOOF tended
      to rank the (manually curated) reference alignment highest among 1060 alternative
      (automatically generated) alignments for a majority of protein families. Among
      the automated alignments, there was a strong positive relationship between the
      WOOF score and similarity to the reference alignment. The speed of WOOF and its
      independence from explicit considerations of three-dimensional structure make it
      an excellent tool for analyzing large numbers of protein families. AVAILABILITY:
      On request from the authors.

PMID- 15728119
TI  - AutoMotif server: prediction of single residue post-translational modifications
      in proteins.
AB  - The AutoMotif Server allows for identification of post-translational modification
      (PTM) sites in proteins based only on local sequence information. The local
      sequence preferences of short segments around PTM residues are described here as
      linear functional motifs (LFMs). Sequence models for all types of PTMs are
      trained by support vector machine on short-sequence fragments of proteins in the
      current release of Swiss-Prot database (phosphorylation by various protein
      kinases, sulfation, acetylation, methylation, amidation, etc.). The accuracy of
      the identification is estimated using the standard leave-one-out procedure. The
      sensitivities for all types of short LFMs are in the range of 70%. AVAILABILITY:
      The AutoMotif Server is available free for academic use at
      http://automotif.bioinfo.pl/

PMID- 15728120
TI  - PatGen--a consolidated resource for searching genetic patent sequences.
AB  - Compared to the wealth of online resources covering genomic, proteomic and
      derived data the Bioinformatics community is rather underserved when it comes to
      patent information related to biological sequences. The current online resources
      are either incomplete or rather expensive. This paper describes, PatGen, an
      integrated database containing data from bioinformatic and patent resources. This
      effort addresses the inconsistency of publicly available genetic patent data
      coverage by providing access to a consolidated dataset. AVAILABILITY: PatGen can
      be searched at http://www.patgendb.com CONTACT: rjdrouse@patentinformatics.com.

PMID- 15728122
TI  - From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic
      potential.
AB  - Reclassification of Hodgkin disease as Hodgkin lymphoma (HL) represents a
      milestone in the lymphoma field, awarding recent insights in the molecular
      biology of Hodgkin and Reed-Sternberg (H-RS) cells and their environment. This
      review summarizes antiapoptotic and proproliferative pathways involved in the
      pathogenesis of this disease with the ultimate goal of translating laboratory
      knowledge into clinical decision making. The focus is on potential targets and
      novel drugs, which are discussed in the context of the complex biology of HL.
      Considering that HL patients are more likely to die from acute and late treatment
      related toxicities than from HL itself, the introduction of targeted,
      biologically based therapies for HL patients with palliative and eventually
      curative intention might be justified.

PMID- 15728121
TI  - The hydration state of human red blood cells and their susceptibility to invasion
      by Plasmodium falciparum.
AB  - In most inherited red blood cell (RBC) disorders with high gene frequencies in
      malaria-endemic regions, the distribution of RBC hydration states is much wider
      than normal. The relationship between the hydration state of circulating RBCs and
      protection against severe falciparum malaria remains unexplored. The present
      investigation was prompted by a casual observation suggesting that falciparum
      merozoites were unable to invade isotonically dehydrated normal RBCs. We designed
      an experimental model to induce uniform and stable isotonic volume changes in RBC
      populations from healthy donors by increasing or decreasing their KCl contents
      through a reversible K(+) permeabilization pulse. Swollen and mildly dehydrated
      RBCs were able to sustain Plasmodium falciparum cultures with similar efficiency
      to untreated RBCs. However, parasite invasion and growth were progressively
      reduced in dehydrated RBCs. In a parallel study, P falciparum invasion was
      investigated in density-fractionated RBCs from healthy subjects and from
      individuals with inherited RBC abnormalities affecting primarily hemoglobin (Hb)
      or the RBC membrane (thalassemias, hereditary ovalocytosis, xerocytosis, Hb CC,
      and Hb CS). Invasion was invariably reduced in the dense cell fractions in all
      conditions. These results suggest that the presence of dense RBCs is a protective
      factor, additional to any other protection mechanism prevailing in each of the
      different pathologies.

PMID- 15728123
TI  - A classification system for cross-reactive material-negative factor XI
      deficiency.
AB  - The bleeding disorder associated with factor XI (fXI) deficiency is typically
      inherited as an autosomal recessive trait. However, some fXI mutations may be
      associated with dominant disease transmission. FXI is a homodimer, a feature that
      could allow certain mutations to exert a dominant-negative effect on wild-type
      fXI secretion through heterodimer formation. We describe 2 novel fXI mutations
      (Ser225Phe and Cys398Tyr) that form intracellular dimers, are secreted poorly,
      and exhibit dominant-negative effects on wild-type fXI secretion in
      cotransfection experiments. Available data now suggest that mutations associated
      with crossreactive material-negative fXI deficiency fall into 1 of 3 mechanistic
      categories: (1) mutations that reduce or prevent polypeptide synthesis, (2)
      polypeptides that fail to form intracellular dimers and are retained in cells as
      monomers, and (3) polypeptides that form dimers that are not secreted. The latter
      category likely accounts for many cases of dominant disease transmission.

PMID- 15728124
TI  - A proportion of patients with lymphoma may harbor mutations of the perforin gene.
AB  - Perforin mutations have been demonstrated in a proportion of patients diagnosed
      with the familial form of hemophagocytic lymphohistiocytosis (HLH). In the
      present study, we evaluated whether some patients with lymphoma sharing clinical
      characteristics with HLH might harbor mutations of the perforin gene. We analyzed
      29 patients and found that 4 patients, who developed either Hodgkin or non
      Hodgkin lymphoma, had biallelic mutations of the perforin gene. One of these 4
      patients, a 19-year-old female with T-cell lymphoma, had a brother carrying the
      same mutations who developed HLH. In 2 of the 4 patients with biallelic mutations
      of the perforin gene, we evaluated perforin expression by flow cytometry and
      natural killer (NK) activity and both were found to be absent. Moreover, we
      documented the presence of monoallelic mutations of the perforin gene in 4 more
      patients. One of these 4 latter patients also carried a mutation of the Fas gene.
      These data indicate that perforin deficiency, either alone or in combination with
      other mutations of genes involved in lymphocyte survival or functional activity,
      may be present in patients with lymphoma. These findings suggest that perforin
      also plays a key role in the mechanisms of immune surveillance that prevent tumor
      growth and/or development.

PMID- 15728125
TI  - An inducible caspase 9 safety switch for T-cell therapy.
AB  - The efficacy of adoptive T-cell therapy as treatment for malignancies may be
      enhanced by genetic modification of infused cells. However, oncogenic events due
      to vector/transgene integration, and toxicities due to the infused cells
      themselves, have tempered enthusiasm. A safe and efficient means of removing
      aberrant cells in vivo would ameliorate these concerns. We describe a "safety
      switch" that can be stably and efficiently expressed in human T cells without
      impairing phenotype, function, or antigen specificity. This reagent is based on a
      modified human caspase 9 fused to a human FK506 binding protein (FKBP) to allow
      conditional dimerization using a small molecule pharmaceutical. A single 10-nM
      dose of synthetic dimerizer drug induces apoptosis in 99% of transduced cells
      selected for high transgene expression in vitro and in vivo. This system has
      several advantages over currently available suicide genes. First, it consists of
      human gene products with low potential immunogenicity. Second, administration of
      dimerizer drug has no effects other than the selective elimination of transduced
      T cells. Third, inducible caspase 9 maintains function in T cells overexpressing
      antiapoptotic molecules. These characteristics favor incorporation of inducible
      caspase 9 as a safety feature in human T-cell therapies.

PMID- 15728127
TI  - HIV-1 incorporates ABO histo-blood group antigens that sensitize virions to
      complement-mediated inactivation.
AB  - ABO histo-blood group antigens have been postulated to modify pathogen spread
      through the action of natural antibodies and complement. The antigens are
      generated by a polymorphic glycosyl-transferase encoded by 2 dominant active and
      a recessive inactive allele. In this study we investigated whether ABO sugars are
      incorporated into the envelope of HIV-1 virions. HIV vectors derived from cells
      expressing ABO antigens displayed sensitivity to fresh human serum analogous to
      ABO incompatibility, and ABO histo-blood group sugars were detected on the viral
      envelope protein, glycoprotein 120 (gp120). Moreover, lymphocyte-derived virus
      also displayed serum sensitivity, reflecting the ABO phenotype of the host when
      cultured in autologous serum due to adsorption of antigens to cell surfaces.
      Serum sensitivity required both active complement and specific anti-ABO
      antibodies. Thus, incorporation of ABO antigens by HIV-1 may affect transmission
      of virus between individuals of discordant blood groups by interaction with host
      natural antibody and complement.

PMID- 15728126
TI  - Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with
      paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of
      multiple myeloma cells.
AB  - Despite major advances, multiple myeloma (MM) remains an incurable malignancy.
      Recently we have found that disease stabilization was achieved in 64% of patients
      with advanced MM treated with the farnesyltransferase inhibitor R115777
      (Zarnestra) in a phase 2 clinical trial. In order to enhance R115777 antitumor
      activity in MM, we examined the combination of this novel agent with other
      anticancer drugs in MM cell lines. In this study, R115777 was found to synergize
      with paclitaxel and docetaxel, but not with other chemotherapy agents, including
      doxorubicin, 5-fluorouracil, cisplastin, melphalan, mitoxantrone, and
      dexamethasone. R115777 synergized with paclitaxel to inhibit MM cell
      proliferation and to induce apoptosis. Synergism in the induction of apoptosis
      was accompanied by increase in cytochrome c release and caspase-3 activation.
      Furthermore, flow cytometry analysis also showed that paclitaxel and R115777
      synergized to induce G(2)/M cell-cycle arrest. Importantly, synergism was
      observed in taxane- and R115777-resistant MM cells. In the human severe combined
      immunodeficient (SCID-hu) bone model of myeloma growth, the ability of paclitaxel
      to inhibit tumor growth in vivo was enhanced by R115777. Combination of
      paclitaxel or docetaxel with R115777 in the treatment of MM cells from patients
      with multiple myeloma was more beneficial than treatment with single agents. Our
      results provide the basis for combination therapy clinical trials with paclitaxel
      or docetaxel with R115777 in MM patients.

PMID- 15728128
TI  - The homeobox gene HEX regulates proliferation and differentiation of
      hemangioblasts and endothelial cells during ES cell differentiation.
AB  - In this report we have investigated the role of the homeobox gene Hex in the
      development and differentiation of the blast colony-forming cell (BL-CFC), a
      progenitor with hemangioblast characteristics generated in embryonic stem (ES)
      cell-derived embryoid bodies (EBs). Molecular analysis showed that Hex is
      expressed in mesoderm, in populations that contain BL-CFCs, and in blast cell
      colonies, the progeny of the BL-CFCs. Hex(-/-) EBs displayed a defect in
      macrophage development but generated higher numbers of BL-CFCs than did wild-type
      EBs. In addition to differences in these progenitor populations, we also found
      that endothelial cells from the Hex(-/-) EBs showed enhanced proliferative
      potential compared with those from wild-type EBs. Forced expression of Hex at the
      onset of ES cell differentiation resulted in reduced EB cellularity, fetal liver
      kinase-1 (Flk-1) expression, and BL-CFC development. Taken together, these
      findings demonstrate that Hex functions at multiple stages of development within
      the differentiating EBs and uncover a novel role for this transcription factor as
      a negative regulator of the hemangioblast and the endothelial lineage.

PMID- 15728129
TI  - A subset of natural killer cells achieves self-tolerance without expressing
      inhibitory receptors specific for self-MHC molecules.
AB  - It is widely believed that self-tolerance of natural killer (NK) cells occurs
      because each NK cell expresses at least one inhibitory receptor specific for a
      host major histocompatibility complex (MHC) class I molecule. Here we report that
      some NK cells lack all known self-MHC-specific inhibitory receptors, yet are
      nevertheless self-tolerant. These NK cells exhibit a normal cell surface
      phenotype and some functional activity. However, they respond poorly to class I
      deficient normal cells, tumor cells, or cross-linking of stimulatory receptors,
      suggesting that self-tolerance is established by dampening stimulatory signaling.
      Thus, self-tolerance of NK cells in normal animals can occur independently of MHC
      mediated inhibition, and hyporesponsiveness plays a role in self-tolerance of NK
      cells, as also proposed for B and T cells.

PMID- 15728130
TI  - Sustained signaling through the B-cell receptor induces Mcl-1 and promotes
      survival of chronic lymphocytic leukemia B cells.
AB  - The clinical course of chronic lymphocytic leukemia (CLL) differs significantly
      between patients with mutated (M-CLL) and unmutated (U-CLL) immunoglobulin (Ig)
      variable heavy-chain (V(H)) genes, implying a role for B-cell receptor (BCR)
      signaling in the pathogenesis of this disease. We have now investigated
      activation of downstream BCR signaling pathways in U-CLL and M-CLL B cells using
      soluble anti-IgM (sol-IgM) and immobilized anti-IgM (imm-IgM) antibodies as
      models for antigenic stimulation. Ligation of the BCR with sol-IgM induced
      incomplete responses in both CLL subsets, resembling the pattern described for
      tolerant B cells. This response was characterized by transient phosphorylation of
      extracellular signal-related kinase (ERK) and Akt (protein kinase B [PKB]), lack
      of activation of c-JUN NH2-terminal kinase (JNK) and p38 mitogen-activated
      protein kinase (MAPK), and variable activation of phospholipase Cgamma2
      (PLCgamma2) and nuclear factor-kappaB (NF-kappaB). Stimulation with imm-IgM
      elicited a more complete BCR signal and significantly prolonged phosphorylation
      of ERK and Akt, indicating persistent or repetitive BCR signaling. Moreover, this
      type of stimulation increased the levels of the antiapoptotic protein myeloid
      cell leukemia-1 (Mcl-1) and protected from chemotherapy-induced apoptosis,
      whereas induction of apoptosis and down-regulation of Mcl-1 was observed
      following stimulation with sol-IgM. These data demonstrate that only sustained
      BCR signaling can promote survival of CLL B cells and indicate that the main
      difference between CLL with mutated and unmutated V(H) genes may reside in the
      availability of such stimulation.

PMID- 15728132
TI  - Xenon: elemental anaesthesia in clinical practice.
AB  - The 'noble' gases have been known to have anaesthetic properties for 50 years yet
      only recently has their application become a clinical reality. In this review we
      describe the preclinical and clinical studies that have led to a resurgence of
      interest in the use of the element xenon as an anaesthetic. Furthermore, we
      highlight specific areas where xenon demonstrates advantages over other
      anaesthetics, including safety, beneficial pharmacokinetics, cardiovascular
      stability, analgesia and neuroprotection.

PMID- 15728131
TI  - Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow.
AB  - Plasmacytoid dendritic cells (pDCs) competent to make type I interferon were
      rigorously defined as a Ly-6C(+) and CD11c(Lo) subset of the B220(+)CD19(-)
      CD43(+)CD24(Lo) bone marrow (BM) Fraction A. Otherwise similar Ly6C(-) cells
      expressed the natural killer (NK) markers DX5 and NK1.1. pDCs represented a
      stable, discrete, and long-lived population. Stem cells and early lymphoid
      progenitors (ELPs), but not prolymphocytes, were effective precursors of pDCs,
      and their differentiation was blocked by ligation of Notch receptors.
      Furthermore, pDCs were present in the BM of RAG1(-/-), CD127/IL-7Ra(-/-), and
      Pax5(-/-) mice. pDCs in RAG1/GFP knock-in mice could be subdivided, and
      immunoglobulin D(H)-J(H) rearrangements, as well as transcripts for the B-lineage
      related genes Pax5, mb1/CD79a, ebf, and Bcl11a, were identified only in the green
      fluorescent protein-positive (GFP(+)) pDC1 subset. All pDCs expressed terminal
      deoxynucleotidyl transferase (TdT), the ETS transcription factor Spi-B, the
      nuclear factor-kappaB transcription factor RelB, toll-like receptor 9 (TLR9), and
      interferon consensus sequence binding protein (ICSBP)/interferon regulatory
      factor 8 (IRF-8) transcripts; lacked CD16 and granulocyte colony-stimulating
      factor receptor (G-CSFR); and were uniformly interleukin-7 receptor alpha (IL
      7Ralpha(-)) AA4.1(Lo), CD27(-), Flk-2(Lo), c-Kit(-), DX-5(-), and CD11b(-), while
      CD4 and CD8alpha were variable. GFP(+) pDC1 subset was less potent than GFP(-)
      pDC2s in T allostimulation and production of tumor necrosis factor alpha
      (TNFalpha), interferon alpha (IFNalpha), and interleukin-6 (IL-6), while only
      pDC2s made IFNgamma and IL-12 p70. Thus, 2 functionally specialized subsets of
      pDCs arise in bone marrow from progenitors that diverge from B, T, and NK
      lineages at an early stage.

PMID- 15728133
TI  - Social class, gender and psychosocial predictors for early sexual debut among 16
      year olds in Oslo.
AB  - BACKGROUND: Variations in early sexual debut among 16 year olds were investigated
      by social level variables, parental occupation, gender, ethnicity, family
      structure, family functioning, and individual level variables, future
      aspirations, academic and social self-perception, and depressed moods. METHODS:
      The variations in sexual debut were investigated by examining proportions of 16
      year olds reporting their first intercourse before age 16. The data were
      collected by self-reporting questionnaires administered to in-school-youth, in
      Oslo. Multivariate logistic regression analyses were used to test for
      associations. Gender interactions with all variables were tested. RESULTS:
      Overall, 25% reported early debut. Independent effect of social class on
      differences in proportions in early sexual debut were found. Gender interaction
      with social class, ethnicity and academic self-perception as they associate to
      proportions having had early sexual debut, were found. For girls the pattern of
      social class differences was linear and the highest proportions were found among
      working classes. For boys the pattern was U-shaped and upper managerial and
      manual working class youth had similar, higher proportions of early debutants.
      High scores of parental monitoring, future aspirations and academic self-concept
      and low scores of depressed moods, are protective factors. While high social self
      perception is positively associated with early debut for both genders.
      CONCLUSION: Early sexual debut varies according to social class, following gender
      specific patterns, among 16 year olds in Oslo. The negative association between
      early debut and academic self-perception are for boys less influenced by other
      social and individual level factors, than for girls.

PMID- 15728134
TI  - Homing in on the specific phenotype(s) of central respiratory chemoreceptors.
AB  - To some it may seem that we now know less about respiratory chemoreception than
      we did 20 years ago. Back then, it was widely accepted that the central
      respiratory chemoreceptors (CRCs) were located exclusively on or near the surface
      of the ventrolateral medulla (VLMS). Now, instead, it is generally believed that
      there are widespread sites of chemoreception, and there is little agreement on
      when and how each of these sites is involved in respiratory control. However,
      those in the field know that this actually is progress, primarily because we have
      gone from simply identifying candidate regions, to identifying specific neuronal
      subtypes that may be the sensors. In this invited review, we have been asked to
      discuss some of the current controversies in the field. First, we define the
      minimal requirements for a cell to be a CRC, and what assumptions can not be made
      without more data. Then we review the evidence that two neuronal subtypes,
      serotonergic neurones of the midline raphe and glutamatergic neurones of the
      retrotrapezoid nucleus, are chemoreceptors. There is evidence supporting a role
      in respiratory chemoreception for both types of neurone, as well as the other
      candidates, but there is also information that is missing. Future work will need
      to focus on which of the candidates are indeed chemoreceptors, what percentage of
      the overall response each one contributes, and how this percentage varies under
      different conditions.

PMID- 15728135
TI  - Effect of anti-inflammatory and antioxidant drugs on the long-term repair of
      severely injured mouse skeletal muscle.
AB  - Non-steroidal anti-inflammatory drugs are frequently prescribed after skeletal
      muscle injury. It is not known whether this type of medication can interfere with
      muscle repair, although inflammatory response is thought to play an important
      role in this process. Tibialis anterior muscles of mice were injured by myotoxic
      agent (snake venom) or crushed. Then, animals were treated daily for 10-14 days
      with different types of non-steroidal anti-inflammatory and antioxidant drugs.
      The long-term repair was studied 10-42 days after injury by analysing the
      recovery of in situ muscle force production, size of regenerating muscle cells
      and expression of myosin heavy chain. Our results show that diclofenac,
      diferuloylmethane (curcumin), dimethylthiourea or pyrrolidine dithiocarbamate
      treatment did not significantly affect muscle recovery after myotoxic injury (P >
      0.05). Similarly, diferuloylmethane, dimethyl sulphoxide or indomethacin
      administration did not markedly change muscle repair after crush injury. However,
      we noted that high doses (> 2 mg kg(-1)) of diferuloylmethane or indomethacin
      increased lethality and reduced muscle repair after crush injury. In conclusion,
      non-steroidal anti-inflammatory and antioxidant drugs did not exhibit long-term
      detrimental effects on muscle recovery after injury, except at lethal doses.

PMID- 15728136
TI  - Retrotrapezoid nucleus: a litmus test for the identification of central
      chemoreceptors.
AB  - Central chemoreception is the mechanism by which arterial blood P(CO2) is
      detected by the CNS to regulate breathing. Two main theories have been proposed
      to account for the phenomenon. The distributed chemosensitivity theory argues
      that pH sensitivity is a widespread attribute of brainstem neurones and that
      central chemoreception results from the cumulative effects of pH on countless
      neurones. The specialized chemoreceptor theory envisions the existence of small
      and specialized populations of CNS cells (chemoreceptors) that are unique in
      their ability to detect very small pH fluctuations and, via specific connections,
      regulate a respiratory network that is itself unresponsive to pH. The recently
      identified CO2-sensitive neurones of the retrotrapezoid nucleus (RTN) seem to
      possess most of the attributes that one would expect of such chemoreceptors. In
      this review we also suggest that many fewer medullary neurones are intrinsically
      responsive to CO2 in vivo than might have been anticipated from prior
      experimentation in vitro. The properties of RTN neurones provide renewed support
      for the specialized chemoreceptor theory of central chemoreception, proposed in
      the early 1960s. However, many uncertainties remain, especially as regards the
      molecular mechanisms of chemoreception, the type of cell that actually detects pH
      in vivo (neurone, glia or others) and the number and location of bona fide
      central chemoreceptors.

PMID- 15728137
TI  - Genetic analysis of complex cardiovascular traits in the spontaneously
      hypertensive rat.
AB  - Identification of the genetic determinants of common diseases is a major
      challenge for current biomedical research. Combining linkage analyses of
      essentially monogenic cis-regulated expression phenotypes with oligogenic
      intermediate physiological phenotypes represents a promising approach for
      identification of quantitative trait loci at the molecular level. In the present
      review, a genetic analysis of cardiovascular phenotypes studied at several levels
      of complexity in rat recombinant inbred strains is described.

PMID- 15728138
TI  - Chronic intermittent asphyxia increases platelet reactivity in rats.
AB  - Sleep-disordered breathing is associated with chronic intermittent asphyxia and
      with a variety of cardiovascular abnormalities. Cardiovascular morbidity and
      mortality are linked to altered platelet function, and platelet function is
      affected in sleep-disordered breathing. As there is evidence that chronic
      continuous hypoxia may alter platelet number and function, the aim of the present
      study was to test the hypothesis that chronic intermittent asphyxia affects
      platelet count, activation and aggregation. Rats were treated with a hypercapnic
      hypoxic gas mixture (minimum of 6-8% O2, maximum of 10-14% CO2) for 15 s, twice
      per minute for 8 h per day for 3 weeks. Blood was analysed for platelet count,
      platelet activation (CD62p expression using flow cytometry), response to low dose
      ADP, haematocrit, red cell count and haemoglobin concentration. A platelet
      function analyser measured the closure time of an aperture, dependent on platelet
      aggregation. Compared to controls (n = 16), chronic intermittent asphyxia (n =
      13) reduced body weight and increased right ventricular weight but had no
      significant effect on platelet count (control, 880.4 +/- 20.1; treated: 914.1 +/-
      35.2 x 10(3) microl(-1); mean +/- S.E.M.), on the reduction in platelet count in
      response to ADP (control, reduced to 206.7 +/- 49.0; treated, reduced to 193.8 +/
      35.9 x 10(3) microl(-1)), or on the percentage of platelets positive for CD62p
      (control, 5.2 +/- 0.7; treated, 6.0 +/- 0.8%). Chronic intermittent asphyxia
      significantly (P = 0.037) reduced the closure time (control, 90.9 +/- 7.7;
      treated, 77.7 +/- 3.8 s), indicating greater adhesion and aggregation. There was
      no significant difference in haematocrit, red cell count and haemoglobin
      concentration. In conclusion, chronic intermittent asphyxia has no effect on
      platelet count but does increase platelet aggegation in rats. These data support
      the idea that chronic intermittent asphyxia alters platelet function in sleep
      disordered breathing.

PMID- 15728139
TI  - Functional and biochemical modifications in skeletal muscles from malarial mice.
AB  - Although it is well established that patients suffering from malaria experience
      skeletal muscle problems (contracture, aches, fatigue, weakness), detailed
      studies have not been performed to investigate changes in the contractile
      function and biochemical properties of intact and skinned skeletal muscles of
      mammals infected with malaria. To this end, we investigated such features in the
      extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus
      (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei.
      We first studied maximal tetanic force (T(max)) produced by intact control and
      malaria-infected muscles before, during and after fatigue. Triton-skinned muscle
      fibres were isolated from these muscles and used to determine isometric
      contractile features as well as a basic biochemical profile as analysed by silver
      enhanced SDS-PAGE. We found that the T(max) of intact muscles and the maximal
      Ca2+-activated force (F(max)) of Triton-skinned muscle fibres were reduced by
      approximately 50% in malarial muscles. In addition, the contractile proteins of
      Triton-skinned muscle fibres from malarial muscles were significantly less
      sensitive to Ca2+. Biochemical analysis revealed that there was a significant
      loss of essential contractile proteins (e.g. troponins and myosin) in Triton
      skinned muscle fibres from malarial muscles as compared to controls. The
      biochemical alterations (i.e., reduction of essential contractile proteins) seem
      to explain well the functional modifications resolved in both intact muscles and
      Triton-skinned muscle fibres and may provide a suitable paradigm for the
      aetiology of muscle symptoms associated with malaria.

PMID- 15728140
TI  - The latent HIV-1 reservoir in patients undergoing HAART: an archive of pre-HAART
      drug resistance.
AB  - Recent studies on patients with a history of pre-HAART drug resistance, but
      currently on a successful regimen, provided new insights into the dynamics of the
      latent cellular viral reservoir. Results indicated that the latent reservoir is
      an archive, composed of a mixture of wild-type and drug-resistant strains. The
      studies showed that, even after years of successful HAART, the wild-type viral
      strains that circulated before the initiation of the therapy as well as all the
      different drug-resistant viral strains that evolved over time during eventual
      periods of non-suppressive treatment, remain detectable in the proviral
      reservoir. These findings support the hypothesis that during active viral
      replication, new variants, including drug-resistant ones, continuously enter the
      latent viral reservoir. It can be concluded that, as a consequence of the
      lifelong conservation of this latent reservoir, the potency of drugs for which
      resistance once developed will remain reduced, even after years of withdrawal of
      the drug.

PMID- 15728141
TI  - Improving compliance with hospital antibiotic guidelines: a time-series
      intervention analysis.
AB  - OBJECTIVES: This study investigated the impact of a combined intervention
      strategy to improve antimicrobial prescribing at University Hospital Groningen.
      For the intervention, the antimicrobial treatment guidelines were updated and
      disseminated in paperback and electronic format. The credibility of the
      guidelines was improved by consultation with users. In a second phase, academic
      detailing (AD) was used to improve specific areas of low compliance with the
      guidelines. MATERIALS AND METHODS: Prescribing data were prospectively collected
      for 2869 patients receiving 7471 prescriptions for an antimicrobial for an
      infection covered by the guidelines between July 2001 and September 2003. After
      collection of baseline data, the guidelines were actively disseminated in
      February 2002. Next, after a 5 month interval, a second intervention, i.e. an AD
      approach, addressed suboptimal prescribing of ciprofloxacin and co-amoxiclav.
      Segmented regression analysis was used to analyse the interrupted time-series
      data. RESULTS: At baseline, compliance with the drug choice guidelines was 67%.
      The first intervention showed a significant change in the level of compliance of
      +15.5% (95% CI: 8%; 23%). AD did not lead to statistically significant additional
      changes in already high levels +12.5% (95% CI:-3%; 28%) of compliance. Post
      intervention compliance was stable at 86%. CONCLUSIONS: Updating the guidelines
      in close collaboration with the specialists involved followed by active
      dissemination proved to be an efficient way to improve compliance with guideline
      recommendations. An 86% compliance level was achieved in this study without
      compulsory measures. A ceiling effect may have limited the added value of AD.

PMID- 15728142
TI  - Disc diffusion-based screening tests for extended-spectrum beta-lactamases in
      Haemophilus influenzae.
AB  - OBJECTIVES: To establish a suitable screening test for the detection of extended
      spectrum beta-lactamases (ESBLs) in Haemophilus influenzae. METHODS: Double disc
      diffusion tests using cephalosporin discs adjacent to an amoxicillin/clavulanate
      3 microg disc, prediffusion tests, where an amoxicillin/clavulanate 3 microg disc
      was prediffused before being replaced with a cephalosporin disc, and combination
      cephalosporin/clavulanate discs were used to screen recombinant H. influenzae
      expressing cloned ESBLs. Methods initially determined to be suitable were
      validated by testing a range of clinical strains. RESULTS: Enhanced zones around
      cephalosporin discs due to synergy with an adjacent amoxicillin/clavulanate disc
      were not reliably demonstrated with the recombinant H. influenzae strains
      expressing ESBLs. Cefotaxime 5 microg or 30 microg and cefpodoxime 10 microg
      discs prediffused with an amoxicillin/clavulanate 3 microg disc, and cefotaxime
      30 microg/clavulanate 10 microg and cefpodoxime 10 microg/clavulanate 1 microg
      combination discs all gave zone sizes > or = 5 mm greater than the corresponding
      plain disc for all recombinant ESBL-producing strains. None of the clinical
      strains gave enhanced zones. CONCLUSIONS: Cefotaxime 5 or 30 microg or
      cefpodoxime 10 microg discs prediffused with an amoxicillin/clavulanate 3 microg
      disc, or cefotaxime 30 microg/clavulanate 10 microg and cefpodoxime 10
      microg/clavulanate 1 mug combination discs are all suitable for screening H.
      influenzae isolates for the presence of ESBLs. ESBL-producing strains should show
      an increase in zone diameter of > or = 5 mm compared with the corresponding plain
      cephalosporin disc.

PMID- 15728143
TI  - Post-antibiotic effect induced by an antibiotic combination: influence of altered
      susceptibility to individual components.
AB  - OBJECTIVES: The impact of altered susceptibility of an organism to the components
      of an antibiotic combination on post-antibiotic effect (PAE) was studied.
      METHODS: The baseline PAEs expressed by Pseudomonas aeruginosa ATCC 27853 were
      recorded following 1 h of exposure to piperacillin and gentamicin, alone and in
      combination. Similar PAE assessments were made after resistance to the individual
      antibiotics was induced over 0.5-2x of their respective MIC. RESULTS: Before any
      induction, the PAE produced by piperacillin alone was negligible and that by the
      combination was synergistic. After piperacillin resistance was induced, PAE
      exhibited by the beta-lactam remained negligible, and comparable PAEs were
      observed for gentamicin and the combination, suggesting an additive interaction
      with a dominant effect from gentamicin. When resistance was induced against
      gentamicin, progressively shorter PAE was expressed by the aminoglycoside alone
      and the combination at increasing levels of resistance. In addition, a measurable
      PAE was unexpectedly observed for piperacillin, whereas the interaction also
      became additive. CONCLUSIONS: In summary, the PAE expressed by the test
      combination was highly dependent on the status of gentamicin resistance. The
      resistance profile exhibited by the organism against individual antibiotics of
      the combination showed an impact on the type of interaction expressed.

PMID- 15728144
TI  - Efficacy of micafungin against deep-seated candidiasis in cyclophosphamide
      induced immunosuppressed mice.
AB  - OBJECTIVES: We investigated the effects of fluconazole and micafungin for the
      therapy of deep-seated candidiasis in a cyclophosphamide-induced immunosuppressed
      mouse model. METHODS: We used the experimental model of intraperitoneal fungal
      abscess caused by Candida albicans, as described previously. RESULTS AND
      CONCLUSIONS: Micafungin efficacy was equal to that of fluconazole in one-tenth
      dosage even in peritonitis. We also assessed the short-term (24 h) and long-term
      (8 days) therapeutic effects after the end of therapy. Although the therapeutic
      effect of fluconazole was similar to that of micafungin at 24 h after the end of
      therapy, the effect of micafungin was superior to that of fluconazole at 8 days
      after the end of therapy.

PMID- 15728145
TI  - Distribution of metronidazole in muscle tissue of patients with septic shock and
      its efficacy against Bacteroides fragilis in vitro.
AB  - OBJECTIVES: Studies investigating the target site concentration of antibiotics,
      such as beta-lactams and fluoroquinolones, have demonstrated differences between
      the drug concentrations in healthy volunteers and septic patients. The aims of
      this study were (i) to evaluate the muscle tissue concentration of metronidazole
      in patients with septic shock and (ii) to test the efficacy of metronidazole in
      an in vitro pharmacodynamic model at different single doses. MATERIALS AND
      METHODS: Six patients admitted to the ICU of Tartu University Clinics with a
      diagnosis of septic shock were studied. Patients receiving metronidazole
      treatment within 48 h before the study or with a BMI > 35 were excluded.
      Metronidazole muscle tissue concentration was assessed by a microdialysis
      technique. Based on the microdialysis data, similar kinetics were simulated in in
      vitro experiments using Bacillus fragilis strains with MIC(90)s of 0.125 mg/L
      (BF125) and 1.0 mg/L (BF1). RESULTS: Metronidazole concentrations in plasma
      achieved a mean (s.d.) value of 11.4+/-2.0 mg/L at 30 min after administration of
      a single 500 mg intravenous dose, while in the muscle tissue, maximum
      concentrations of 8.2+/-4.5 mg/L were achieved at 140+/-92.3 min after the dose.
      When this metronidazole time course was simulated in vitro, the time to 99.9%
      kill ranged from 1.0 to 1.4 h for BF125 and from 1.8 to 3.5 h for BF1, while the
      eradication time ranged from 1.7 to 2.5 h and from 3.4 to 6.5 h, respectively. No
      regrowth was detected. CONCLUSION: Pharmacokinetic-pharmacodynamic simulation of
      metronidazole interstitial concentrations shows a high efficacy of the drug in
      septic patients.

PMID- 15728146
TI  - Economic evaluation of voriconazole compared with conventional amphotericin B for
      the primary treatment of aspergillosis in immunocompromised patients.
AB  - OBJECTIVE: The objective of this study was to conduct an economic evaluation of
      voriconazole compared with conventional amphotericin B deoxycholate (CAB) using
      data from a recently reported randomized comparative trial in patients with
      various underlying immunosuppressive conditions. This trial demonstrated the
      superiority of voriconazole in terms of clinical response, survival and safety
      when used as primary therapy for invasive aspergillosis. METHODS: A decision
      analytic model was designed using an expert panel and populated primarily with
      efficacy and resource utilization data collected prospectively during the
      clinical trial. The analysis was carried out from the perspective of the health
      care system and all costs are reported in 2002 US dollars. RESULTS: Average total
      treatment costs per patient were 10% lower in the voriconazole arm ($30 664) than
      in the CAB arm ($34 144), resulting from reduced consumption of hospital
      resources and fewer changes in antifungal therapy. In the base case analysis,
      voriconazole provided an average saving of $3481 per treated patient, resulted in
      a lower cost per survivor ($43 310 versus $58 971) and a lower cost per
      successfully treated patient ($58 100 versus $108 124) compared with CAB.
      Sensitivity analyses demonstrated that the cost savings observed were maintained
      over a wide range of alternative values for both unit costs and resource
      utilization, including length of hospital stay, time spent in intensive care
      units, bed day costs and the cost of lipid formulations of amphotericin B.
      CONCLUSION: Incremental cost-effectiveness analysis indicated the dominance of
      voriconazole because of both lower costs and greater efficacy.

PMID- 15728147
TI  - Pharmacokinetic interaction between chemotherapy for non-Hodgkin's lymphoma and
      protease inhibitors in HIV-1-infected patients.
AB  - OBJECTIVES: We have investigated whether chemotherapy for HIV-related systemic
      non-Hodgkin's lymphoma (NHL) affects the pharmacokinetics of protease inhibitors.
      PATIENTS AND METHODS: This was a prospective, open-label, non-randomized, two-way
      crossover trial in HIV-1-infected patients treated with highly active
      antiretroviral therapy and chemotherapy for NHL. Seven patients received
      indinavir at a dosage of 800 mg three times daily and three patients received
      nelfinavir at a dosage of 750 mg three times daily. Chemotherapy consisted of
      adriamycin, cyclophosphamide, vincristine and prednisolone (CHOP). Each patient
      had blood samples for protease inhibitor pharmacokinetics drawn concomitantly
      with or independently of the CHOP cycle. RESULTS: When indinavir was given
      concomitantly with CHOP, the AUC(0-8) increased by 38% (20.5 +/- 9.0 versus 14.9
      +/- 9.5 mg.h/L; P=0.03), and was comparable to historical controls. By contrast,
      the AUC(0-8) of indinavir administered without CHOP was lower than expected. A
      similar trend was observed with nelfinavir. Likewise, we observed a significant
      number of patients with C(0) and C(8) below the IC(50) for the wild-type virus
      (0.1 mg/L) when the drug was administered without CHOP. CONCLUSIONS: Therapeutic
      drug monitoring of protease inhibitors should be part of the work-up in HIV
      infected patients receiving chemotherapy for NHL.

PMID- 15728148
TI  - Emergence of Neisseria meningitidis with decreased susceptibility to
      ciprofloxacin in Argentina.

PMID- 15728149
TI  - First linezolid- and vancomycin-resistant Enterococcus faecium strain in Taiwan.

PMID- 15728150
TI  - Fluoroquinolone-resistant Pseudomonas aeruginosa: risk factors for acquisition
      and impact on outcomes.
AB  - OBJECTIVES: Resistance among Pseudomonas aeruginosa has risen dramatically and
      parallels the increase in fluoroquinolone (FQ) prescribing in recent years. Risk
      factors for FQ resistance in P. aeruginosa and its impact on outcomes need to be
      well characterized. METHODS: A case-control study was carried out on hospitalized
      adult patients from whom FQ-resistant (case) and FQ-susceptible (control) P.
      aeruginosa were isolated. RESULTS: A total of 177 patients with positive cultures
      (91 cases and 86 controls) and 119 with documented infections (65 cases, 54
      controls) were included in risk factor and outcomes analysis, respectively.
      Independent risk factors for FQ resistance were: FQ exposure (OR 12.6, CI 4.95
      32), nosocomial acquisition (OR 8.6, CI 3.5-20.7), and diabetes mellitus (OR 6.4,
      CI 2.1-19.3). An FQ agent was prescribed in 59% of patients receiving an
      'antipseudomonal' empirical regimen. Compared with controls, FQ-resistant cases
      had a median delay to receiving effective therapy of 3.5 days versus 1 day and
      poorer outcomes: (i) lower complete response rate (45% versus 63%, P=0.04); (ii)
      longer time to achieve clinical stability (8 days versus 3 days, P=0.005); and
      (iii) higher infection-related mortality (21% versus 7%; OR = 2.9, 0.9-9.4).
      Empirical FQ use (OR 4.6, CI 1.5-14.3), FQ resistance (OR 3.6, CI 1.0-13.1), and
      high APACHE II score (OR 1.1, CI 1.0-1.2) were independent risk factors for
      increased mortality. CONCLUSIONS: FQ exposure from widespread prescribing is a
      modifiable risk factor for FQ resistance in P. aeruginosa. FQ empirical therapy
      for Pseudomonas infections may be associated with significant delays in
      administering effective therapy resulting in adverse outcomes.

PMID- 15728151
TI  - The cover. The Dry River.

PMID- 15728152
TI  - Michael E. DeBakey, MD: father of modern cardiovascular surgery.

PMID- 15728153
TI  - Experts charge new US dietary guidelines pose daunting challenge for the public.

PMID- 15728161
TI  - Surveillance of BRCA1 and BRCA2 carriers.

PMID- 15728162
TI  - Cocaine and phenylephrine eye drop test for Parkinson disease.

PMID- 15728163
TI  - Neurodevelopmental impairment and neonatal infections.

PMID- 15728164
TI  - Effects of estrogen with and without progestin on urinary incontinence.
AB  - CONTEXT: Menopausal hormone therapy has long been credited with many benefits
      beyond the indications of relieving hot flashes, night sweats, and vaginal
      dryness, and it is often prescribed to treat urinary incontinence (UI).
      OBJECTIVE: To assess the effects of menopausal hormone therapy on the incidence
      and severity of symptoms of stress, urge, and mixed UI in healthy postmenopausal
      women. DESIGN, SETTING, AND PARTICIPANTS: Women's Health Initiative multicenter
      double-blind, placebo-controlled, randomized clinical trials of menopausal
      hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled
      between 1993 and 1998, for whom UI symptoms were known in 23,296 participants at
      baseline and 1 year. INTERVENTIONS: Women were randomized based on hysterectomy
      status to active treatment or placebo in either the estrogen plus progestin (E +
      P) or estrogen alone trials. The E + P hormones were 0.625 mg/d of conjugated
      equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (CEE + MPA);
      estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen (CEE). There
      were 8506 participants who received CEE + MPA (8102 who received placebo) and
      5310 who received CEE alone (5429 who received placebo). MAIN OUTCOME MEASURES:
      Incident UI at 1 year among women without UI at baseline and severity of UI at 1
      year among women who had UI at baseline. RESULTS: Menopausal hormone therapy
      increased the incidence of all types of UI at 1 year among women who were
      continent at baseline. The risk was highest for stress UI (CEE + MPA: relative
      risk [RR], 1.87 [95% confidence interval {CI}, 1.61-2.18]; CEE alone: RR, 2.15
      [95% CI, 1.77-2.62]), followed by mixed UI (CEE + MPA: RR, 1.49 [95% CI, 1.10
      2.01]; CEE alone: RR, 1.79 [95% CI, 1.26-2.53]). The combination of CEE + MPA had
      no significant effect on developing urge UI (RR, 1.15; 95% CI, 0.99-1.34), but
      CEE alone increased the risk (RR, 1.32; 95% CI, 1.10-1.58). Among women
      experiencing UI at baseline, frequency worsened in both trials (CEE + MPA: RR,
      1.38 [95% CI, 1.28-1.49]; CEE alone: RR, 1.47 [95% CI, 1.35-1.61]). Amount of UI
      worsened at 1 year in both trials (CEE + MPA: RR, 1.20 [95% CI, 1.06-1.36]; CEE
      alone: RR, 1.59 [95% CI, 1.39-1.82]). Women receiving menopausal hormone therapy
      were more likely to report that UI limited their daily activities (CEE + MPA: RR,
      1.18 [95% CI, 1.06-1.32]; CEE alone: RR, 1.29 [95% CI, 1.15-1.45]) and bothered
      or disturbed them (CEE + MPA: RR, 1.22 [95% CI, 1.13-1.32]; CEE alone: RR, 1.50
      [95% CI, 1.37-1.65]) at 1 year. CONCLUSIONS: Conjugated equine estrogen alone and
      CEE + MPA increased the risk of UI among continent women and worsened the
      characteristics of UI among symptomatic women after 1 year. Conjugated equine
      estrogen with or without progestin should not be prescribed for the prevention or
      relief of UI.

PMID- 15728165
TI  - Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated
      cystitis in women: a randomized trial.
AB  - CONTEXT: The high prevalence of resistance to trimethoprim-sulfamethoxazole and
      other antimicrobials among Escherichia coli causing acute cystitis in women has
      led to increased use of alternative antibiotics. One such antibiotic, amoxicillin
      clavulanate, has not been well studied. OBJECTIVE: To compare the efficacy of a 3
      day regimen of amoxicillin-clavulanate to that of a 3-day regimen of
      ciprofloxacin in the treatment of acute cystitis in women. The primary study
      hypothesis was that the amoxicillin-clavulanate and ciprofloxacin treatment
      groups would differ in clinical cure. DESIGN, SETTING, AND PATIENTS: Randomized,
      single-blind treatment trial of 370 women, aged 18 to 45 years, with symptoms of
      acute uncomplicated cystitis and a urine culture with at least 10(2) colony
      forming units of uropathogens per milliliter from a university student health
      center or a health maintenance organization. INTERVENTIONS: Women were randomly
      assigned to receive amoxicillin-clavulanate (500 mg/125 mg twice daily) or
      ciprofloxacin (250 mg twice daily) for 3 days and were followed up for 4 months.
      MAIN OUTCOME MEASURES: The main outcome measure was clinical cure. Secondary
      study outcomes of interest were microbiological cure and vaginal E coli
      colonization at the 2-week follow-up visit. RESULTS: Clinical cure was observed
      in 93 (58%) of 160 women treated with amoxicillin-clavulanate compared with 124
      (77%) of 162 women treated with ciprofloxacin (P<.001). Amoxicillin-clavulanate
      was not as effective as ciprofloxacin even among women infected with strains
      susceptible to amoxicillin-clavulanate (65 [60%] of 109 women in the amoxicillin
      clavulanate group vs 114 [77%] of 149 women in the ciprofloxacin group; P =
      .004). The difference in clinical cure rates occurred almost entirely within the
      first 2 weeks after therapy. Microbiological cure at 2 weeks was observed in 118
      (76%) of 156 women treated with amoxicillin-clavulanate compared with 153 (95%)
      of 161 women treated with ciprofloxacin (P<.001). At this visit, 45% of women in
      the amoxicillin-clavulanate group compared with 10% in the ciprofloxacin group
      had vaginal colonization with E coli (P<.001). CONCLUSIONS: A 3-day regimen of
      amoxicillin-clavulanate is not as effective as ciprofloxacin for the treatment of
      acute uncomplicated cystitis, even in women infected with susceptible strains.
      This difference may be due to the inferior ability of amoxicillin-clavulanate to
      eradicate vaginal E coli, facilitating early reinfection.

PMID- 15728166
TI  - Screening for bipolar disorder in a primary care practice.
AB  - CONTEXT: Bipolar disorder consists of episodes of manic and depressive symptoms.
      Efforts to screen for depression in a primary care setting without assessment of
      past manic symptoms can lead to incorrect diagnosis and treatment of bipolar
      disorder. OBJECTIVES: To screen for bipolar disorder in adult primary care
      patients and to examine its clinical presentation and effect on functioning.
      DESIGN, SETTING, AND PARTICIPANTS: A systematic sample of 1157 patients between
      18 and 70 years of age who were seeking primary care at an urban general medicine
      clinic serving a low-income population. The study was conducted between December
      2001 and January 2003. MAIN OUTCOME MEASURES: Prevalence of bipolar disorder, its
      treatment and patient functioning. Study measures included the Mood Disorder
      Questionnaire, the PRIME-MD Patient Health Questionnaire, the Medical Outcomes
      Study 12-Item Short Form health survey, the Sheehan Disability Scale, data on
      past mental health treatments, and a review of medical records and International
      Classification of Diseases, Ninth Revision codes for each visit dating from 6
      months prior to the screening day. RESULTS: The prevalence of receiving positive
      screening results for lifetime bipolar disorder was 9.8% (n = 112; 95% confidence
      interval, 8.0%-11.5%) and did not differ significantly by age, sex, or
      race/ethnicity. Eighty-one patients (72.3%) who screened positive for bipolar
      disorder sought professional help for their symptoms, but only 9 (8.4%) reported
      receiving a diagnosis of bipolar disorder. Seventy-five patients (68.2%) who
      screened positive for bipolar disorder had a current major depressive episode or
      an anxiety or substance use disorder. Of 112 patients, only 7 (6.5%) reported
      taking a mood-stabilizing agent in the past month. Primary care physicians
      recorded evidence of current depression in 47 patients (49.0%) who screened
      positive for bipolar disorder, but did not record a bipolar disorder diagnosis
      either in administrative billing or the medical record of any of these patients.
      Patients who screened positive for bipolar disorder reported worse health-related
      quality of life as well as increased social and family life impairment compared
      with those who screened negative. CONCLUSIONS: In an urban general medicine
      clinic, a positive screen for bipolar disorder appears to be common, clinically
      significant, and underrecognized. Because of the risks associated with treating
      bipolar disorder with antidepressant monotherapy, efforts are needed to educate
      primary care physicians about the screening, management, and pharmacotherapy of
      bipolar disorders.

PMID- 15728167
TI  - Prevalence of BRCA1 and BRCA2 mutations in women diagnosed with ductal carcinoma
      in situ.
AB  - CONTEXT: The distribution of BRCA1 and BRCA2 mutations in women diagnosed with
      noninvasive breast carcinoma is unknown. OBJECTIVE: To estimate the BRCA1 and
      BRCA2 mutation prevalence in women with ductal carcinoma in situ (DCIS),
      unselected for age, family history, or ethnicity. DESIGN, SETTING, AND
      PARTICIPANTS: The data were 369 DCIS cases diagnosed among female residents aged
      20 to 79 years from the state of Connecticut between September 15, 1994, and
      March 14, 1998. These women were participants in a large population-based case
      control study of breast carcinoma in situ. Telephone interviews were used to
      collect risk factor information and blood or buccal specimens were collected for
      BRCA1 and BRCA2 mutation testing. MAIN OUTCOME MEASURES: Prevalence of disease
      associated mutations of BRCA1 and BRCA2 in women diagnosed with DCIS. RESULTS:
      Three (0.8%) and 9 (2.4%) of 369 DCIS cases had disease-associated mutations in
      BRCA1 or BRCA2, respectively. One woman had a mutation in both genes (BRCA1 W321X
      and BRCA2 3398del5). Carriers were significantly more likely than noncarriers to
      report a first-degree (mother, sister, or daughter) family history of breast
      cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.4), as well as
      a personal history of ovarian cancer. In addition, carriers were more likely than
      noncarriers to be diagnosed at an early age (<50 years) (OR, 3.4; 95% CI, 1.0
      11.7), as well as to report at least 1 first-degree relative diagnosed with
      breast cancer before 50 years (OR, 10.6; 95% CI, 3.0-37.0). CONCLUSIONS: Ductal
      carcinoma in situ is a part of the breast/ovarian cancer syndromes defined by
      BRCA1 and BRCA2, with mutation rates similar to those found for invasive breast
      cancer. These findings suggest that patients with breast cancer with an
      appropriate personal or family history of breast and/or ovarian cancer should be
      screened and followed according to high-risk protocols, regardless of whether
      they are diagnosed with in situ or invasive breast cancer.

PMID- 15728168
TI  - Evaluation of new treatments in radiation oncology: are they better than standard
      treatments?
AB  - CONTEXT: The superiority of innovative over standard treatments is not known. To
      describe accurately the outcomes of innovations that are tested in randomized
      controlled trials (RCTs) 3 factors have to be considered: publication rate,
      quality of trials, and the choice of the adequate comparator intervention.
      OBJECTIVE: To determine the success rate of innovative treatments by assessing
      preferences between experimental and standard treatments according to original
      investigators' conclusions, determining the proportion of RCTs that achieved
      primary outcomes' statistical significance, and performing meta-analysis to
      examine if the summary point estimate favored innovative vs standard treatments.
      DATA SOURCES: Randomized controlled trials conducted by the Radiation Therapy
      Oncology Group (RTOG). STUDY SELECTION: All completed phase 3 trials conducted by
      the RTOG since its creation in 1968 until 2002. For multiple publications of the
      same study, we used the one with the most complete primary outcomes and with the
      longest follow-up information. DATA EXTRACTION: We used the US National Cancer
      Institute definition of completed studies to determine the publication rate. We
      extracted data related to publication status, methodological quality, and
      treatment comparisons. One investigator extracted the data from all studies and 2
      independent investigators extracted randomly about 50% of the data. Disagreements
      were resolved by consensus during a meeting. DATA SYNTHESIS: Data on 12,734
      patients from 57 trials were evaluated. The publication rate was 95%. The quality
      of trials was high. We found no evidence of inappropriateness of the choice of
      comparator. Although the investigators judged that standard treatments were
      preferred in 71% of the comparisons, when data were meta-analyzed innovations
      were as likely as standard treatments to be successful (odds ratio for survival,
      1.01; 99% confidence interval, 0.96-1.07; P = .5). In contrast, treatment-related
      mortality was worse with innovations (odds ratio, 1.76; 99% confidence interval,
      1.01-3.07; P = .008). We found no predictable pattern of treatment successes in
      oncology: sometimes innovative treatments are better than the standard ones and
      vice versa; in most cases there were no substantive differences between
      experimental and conventional treatments. CONCLUSION: The finding that the
      results in individual trials cannot be predicted in advance indicates that the
      system and rationale for RCTs is well preserved and that successful interventions
      can only be identified after an RCT is completed.

PMID- 15728169
TI  - Pharmacological facilitation of primary percutaneous coronary intervention for
      acute myocardial infarction: is the slope of the curve the shape of the future?
AB  - Current options for reperfusion therapy in patients admitted to a community
      hospital without cardiac catheterization facilities include administration of
      fibrinolytic drugs followed by observation, with referral to angiography driven
      by symptoms and signs of ischemia; transfer to a tertiary care center for primary
      percutaneous coronary intervention (PCI); or a strategy of facilitated PCI in
      which administration of fibrinolytics and platelet glycoprotein IIb/IIIa
      inhibitors (alone or in combination) is followed by transfer for immediate
      angiography and PCI if appropriate. We systematically analyzed multiple
      randomized and nonrandomized trials to review the pathophysiology of reperfusion
      therapy in acute myocardial infarction to derive insights about the likelihood of
      success of a strategy of facilitated PCI compared with transfer only or
      fibrinolysis only. The basis for the recommendations made herein is a
      hypothetical curve relating the duration of symptoms before reperfusion to
      reduction in mortality and extent of myocardial salvage. During the first 2 to 3
      hours after symptom onset, a striking benefit of reperfusion is present; within
      this period, time to treatment is critical. Subsequently, a mortality benefit is
      still present but of decreasing magnitude over time. In this situation, the
      priority is to open the artery, and time to treatment is less critical. Results
      of facilitated PCI may depend largely on timing of presentation. If presentation
      is late after symptom onset (ie, on the "flat" part of the curve), there will be
      little mortality benefit from earlier patency and patients will be subject to the
      bleeding risks of fibrinolytic drugs. In contrast, among patients presenting very
      early (60-90 minutes after symptom onset), outcomes with fibrinolytic therapy
      alone are excellent, and it will be difficult for any other strategy to result in
      a significant improvement. But in patients presenting 2 to 3 hours after onset of
      symptoms, a strategy of facilitated PCI may move patients from the plateau to the
      descending limb of the curve, with a substantial improvement in myocardial
      salvage and mortality. Two large ongoing trials may provide definitive answers to
      these issues.

PMID- 15728170
TI  - Does this patient have influenza?
AB  - CONTEXT: Influenza vaccination lowers, but does not eliminate, the risk of
      influenza. Making a reliable, rapid clinical diagnosis is essential to
      appropriate patient management that may be especially important during shortages
      of antiviral agents caused by high demand. OBJECTIVES: To systematically review
      the precision and accuracy of symptoms and signs of influenza. A secondary
      objective was to review the operating characteristics of rapid diagnostic tests
      for influenza (results available in <30 min). DATA SOURCES: Structured search
      strategy using MEDLINE (January 1966-September 2004) and subsequent searches of
      bibliographies of retrieved articles to identify articles describing primary
      studies dealing with the diagnosis of influenza based on clinical signs and
      symptoms. The MEDLINE search used the Medical Subject Headings EXP influenza or
      EXP influenza A virus or EXP influenza A virus human or EXP influenza B virus and
      the Medical Subject Headings or terms EXP sensitivity and specificity or EXP
      medical history taking or EXP physical examination or EXP reproducibility of
      results or EXP observer variation or symptoms.mp or clinical signs.mp or
      sensitivity.mp or specificity.mp. STUDY SELECTION: Of 915 identified articles on
      clinical assessment of influenza-related illness, 17 contained data on the
      operating characteristics of symptoms and signs using an independent criterion
      standard. Of these, 11 were eliminated based on 4 inclusion criteria and
      availability of nonduplicative primary data. DATA EXTRACTION: Two authors
      independently reviewed and abstracted data for estimating the likelihood ratios
      (LRs) of clinical diagnostic findings. Differences were resolved by discussion
      and consensus. DATA SYNTHESIS: No symptom or sign had a summary LR greater than 2
      in studies that enrolled patients without regard to age. For decreasing the
      likelihood of influenza, the absence of fever (LR, 0.40; 95% confidence interval
      [CI], 0.25-0.66), cough (LR, 0.42; 95% CI, 0.31-0.57), or nasal congestion (LR,
      0.49; 95% CI, 0.42-0.59) were the only findings that had summary LRs less than
      0.5. In studies limited to patients aged 60 years or older, the combination of
      fever, cough, and acute onset (LR, 5.4; 95% CI, 3.8-7.7), fever and cough (LR,
      5.0; 95% CI, 3.5-6.9), fever alone (LR, 3.8; 95% CI, 2.8-5.0), malaise (LR, 2.6;
      95% CI, 2.2-3.1), and chills (LR, 2.6; 95% CI, 2.0-3.2) increased the likelihood
      of influenza to the greatest degree. The presence of sneezing among older
      patients made influenza less likely (LR, 0.47; 95% CI, 0.24-0.92). CONCLUSIONS:
      Clinical findings identify patients with influenza-like illness but are not
      particularly useful for confirming or excluding the diagnosis of influenza.
      Clinicians should use timely epidemiologic data to ascertain if influenza is
      circulating in their communities, then either treat patients with influenza-like
      illness empirically or obtain a rapid influenza test to assist with management
      decisions.

PMID- 15728171
TI  - Estrogen treatment for urinary incontinence: never, now, or in the future?

PMID- 15728172
TI  - The case for randomized trials in cancer treatment: new is not always better.

PMID- 15728174
TI  - JAMA patient page. Influenza.

PMID- 15728175
TI  - Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of
      Alzheimer's disease patients.
AB  - Accumulation of Abeta protein in beta-amyloid deposits is a hallmark event in
      Alzheimer's disease (AD). Recent findings suggest anti-Abeta autoantibodies may
      have a role in AD pathology. However, a consensus has yet to emerge as to whether
      endogenous anti-Abeta autoantibodies are elevated, depressed, or unchanged in AD
      patients. Whereas experiments to date have used synthetic unmodified monomeric
      Abeta (Abetamon) to test autoimmunity, up to 40% of the Abeta pool inB AD brain
      consists of low molecular weight oligomeric cross-linked beta-amyloid protein
      species (CAPS). Recent studies also suggest that CAPS may be the primary
      neurotoxic agent in AD. In the present study, AD and nondemented control plasma
      were analyzed for immunoreactivity to CAPS and Abetamon. Plasma of both
      nondemented and AD patients were found to contain autoantibodies specific for
      soluble CAPS. Nondemented control and AD plasmas demonstrated similar
      immunoreactivity to Abetamon. In contrast, anti-CAPS antibodies in AD plasma were
      found to be significantly reduced compared with nondemented controls (p=0.018).
      Furthermore, age at onset for AD correlated significantly (p=0.041) with plasma
      immunoreactivity to CAPS. These data suggest that autoantibodies to CAPS are
      depleted in AD patients and raise the prospect that immunization with anti-CAPS
      antibodies might provide therapeutic benefit for AD.

PMID- 15728176
TI  - Dynamic assembly of the urokinase-type plasminogen activator signaling receptor
      complex determines the mitogenic activity of urokinase-type plasminogen
      activator.
AB  - The urokinase-type plasminogen activator (uPA) receptor (uPAR) functions in
      concert with co-receptors, including integrins, FPR-like receptor-1/lipoxin A4
      receptor, and the epidermal growth factor receptor (EGFR), to initiate cell
      signaling. uPAR co-receptors may be dynamically organized into a multiprotein
      signaling receptor complex. In Chinese hamster ovary-K1 (CHO-K1) cells, uPA
      binding to uPAR activates ERK/MAP kinase, even though these cells do not express
      the EGFR; however, when CHO-K1 cells are transfected to express the EGFR, ERK
      activation becomes EGFR-dependent. In this study, we demonstrate that ERK
      activation in response to uPA follows equivalent biphasic kinetics in EGFR
      expressing and -deficient CHO-K1 cells. In both cell types, the response is
      pertussis toxin-sensitive; however, uPA promotes cell proliferation exclusively
      in the EGFR-expressing cells. uPA-induced mitogenic activity requires activation
      of both STAT5b and ERK. STAT5b was tyrosine-phosphorylated, in response to uPA,
      only in EGFR-expressing cells. uPA-induced cell proliferation was blocked by
      dominant-negative MEK1, dominant-negative STAT5b, and by expression of an EGFR
      that is mutated at Tyr-845, which is essential for STAT5b activation. In two cell
      culture models of uPA-stimulated breast cancer growth, MDA-MB 468 cells treated
      with uPA and MCF-7 cells treated with uPA-plasminogen activator inhibitor-1
      complex, proliferation was completely inhibited when EGFR expression or activity
      was blocked. We conclude that expression and assembly of uPAR co-receptors in a
      specific cell type determines the response to uPA. The EGFR selectively
      cooperates with uPAR to mediate mitogenesis.

PMID- 15728177
TI  - The importance of dynamic effects on the enzyme activity: X-ray structure and
      molecular dynamics of onconase mutants.
AB  - Onconase (ONC), a member of the RNase A superfamily extracted from oocytes of
      Rana pipiens, is an effective cancer killer. It is currently used in treatment of
      various forms of cancer. ONC antitumor properties depend on its ribonucleolytic
      activity that is low in comparison with other members of the superfamily. The
      most damaging side effect from Onconase treatment is renal toxicity, which seems
      to be caused by the unusual stability of the enzyme. Therefore, mutants with
      reduced thermal stability and/or increased catalytic activity may have
      significant implications for human cancer chemotherapy. In this context, we have
      determined the crystal structures of two Onconase mutants (M23L-ONC and
      C87S,des103-104-ONC) and performed molecular dynamic simulations of ONC and
      C87S,des103-104-ONC with the aim of explaining on structural grounds the
      modifications of the activity and thermal stability of the mutants. The results
      also provide the molecular bases to explain the lower catalytic activity of
      Onconase compared with RNase A and the unusually high thermal stability of the
      amphibian enzyme.

PMID- 15728178
TI  - A novel antiestrogenic mechanism in progesterone receptor-transfected breast
      cancer cells.
AB  - The expression of progesterone receptor (PR) is normally estrogen-dependent, and
      progesterone is only active in target cells following estrogen exposure. This
      study revealed that the effect of estrogen was markedly disrupted by estrogen
      independent expression of PR. Transfection of PR in estrogen receptor (ER)
      positive MCF-7 cells abolished the estradiol-17beta growth stimulatory effect
      that was observed in the parental cells and the vector-transfected controls in a
      ligand-independent manner. The antiestrogenic effect was also observed at the
      level of gene transcription. Estradiol-17beta (E2)-induced gene expression of pS2
      and GREB1 was impaired by 50-75% after 24-72 h of E2 treatment in PR-transfected
      cells. Promoter interference assay revealed that PR transfection drastically
      inhibited E2-mediated ER binding to estrogen response elements (ERE). The
      antiestrogenic effects of transfected PR are associated with enhanced metabolism
      of E2. HPLC analysis of [3H]E2 in the samples indicated that the percentage of
      [3H]E2 metabolized by PR-transfected cells in 6 h is similar to that by vector
      transfected control cells in 24 h (77 and 80%, respectively). The increased
      metabolism of E2 may, in turn, be caused by increased cellular uptake of E2, as
      demonstrated by whole cell binding of [3H]E2. The findings open up a new window
      for a hitherto unknown functional relationship between the PR and ER. The
      antiestrogenic effect of transfected PR also provides a potential therapeutic
      strategy for estrogen-dependent breast cancer.

PMID- 15728179
TI  - Functional dissection of an AP-2 beta2 appendage-binding sequence within the
      autosomal recessive hypercholesterolemia protein.
AB  - The autosomal recessive hypercholesterolemia (ARH) protein plays a critical role
      in regulating plasma low density lipoprotein (LDL) levels. Inherited defects in
      ARH lead to a hypercholesterolemia that closely phenocopies that caused by a
      defective LDL receptor. The elevated serum LDL-cholesterol levels typical of ARH
      patients and the pronounced accumulation of the LDL receptor at the cell surface
      of hepatocytes in ARH-null mice argue that ARH operates by promoting the
      internalization of the LDL receptor within clathrin-coated vesicles. ARH contains
      an amino-terminal phosphotyrosine-binding domain that associates physically with
      the LDL receptor internalization sequence and with phosphoinositides. The
      carboxyl-terminal half of ARH contains a clathrin-binding sequence and a separate
      AP-2 adaptor binding region providing a plausible mechanism for how ARH can act
      as an endocytic adaptor or CLASP (clathrin-associated sorting protein) to couple
      LDL receptors with the clathrin machinery. Because the interaction with AP-2 is
      highly selective for the independently folded appendage domain of the beta2
      subunit, we have characterized the ARH beta2 appendage-binding sequence in
      detail. Unlike the known alpha appendage-binding motifs, ARH requires an
      extensive sequence tract to bind the beta appendage with comparably high
      affinity. A minimal 16-residue sequence functions autonomously and depends upon
      ARH residues Asp253, Phe259, Leu262, and Arg266. We suggested that biased beta
      subunit engagement by ARH and the only other beta2 appendage selective adaptor,
      beta-arrestin, promotes efficient incorporation of this mechanistically distinct
      subset of CLASPs into clathrin-coated buds.

PMID- 15728180
TI  - Proteolysis of macrophage inflammatory protein-1alpha isoforms LD78beta and
      LD78alpha by neutrophil-derived serine proteases.
AB  - Macrophage inflammatory protein-1alpha (MIP-1alpha) is a chemokine that leads to
      leukocyte recruitment and activation at sites of infection. Controlling chemokine
      activity at sites of infection is important, since excess accumulation of
      leukocytes may contribute to localized tissue damage. Neutrophil-derived serine
      proteases modulate the bioactivity of chemokine and cytokine networks through
      proteolytic cleavage. Because MIP-1alpha is temporally expressed with neutrophils
      at sites of infection, we examined proteolysis of MIP-1alpha in vitro by the
      neutrophil-derived serine proteases: cathepsin G, elastase, and proteinase 3.
      Recombinant human MIP-1alpha isoforms LD78beta and LD78alpha were expressed and
      purified, and the protease cleavage sites were analyzed by mass spectrometry and
      peptide sequencing. Chemotactic activities of parent and cleavage molecules were
      also compared. Both LD78beta and LD78alpha were cleaved by neutrophil lysates at
      Thr16-Ser17, Phe24-Ile25, Tyr28-Phe29, and Thr31-Ser32. This degradation was
      inhibited by serine protease inhibitors phenylmethylsulfonyl fluoride and 4-(2
      aminoethyl)-benzenesulfonyl fluoride. Incubation of the substrates with
      individual proteases revealed that cathepsin G preferentially cleaved at Phe24
      Ile25 and Tyr28-Phe29, whereas elastase and proteinase 3 cleaved at Thr16-Ser17
      and Thr31-Ser32. Proteolysis of LD78beta resulted in loss of chemotactic
      activity. The role of these proteases in LD78beta and LD78alpha degradation was
      confirmed by incubation with neutrophil lysates from Papillon-Lefevre syndrome
      patients, demonstrating that the cell lysates containing inactivated serine
      proteases could not degrade LD78beta and LD78alpha. These findings suggest that
      severe periodontal tissue destruction in Papillon-Lefevre syndrome may be related
      to excess accumulation of LD78beta and LD78alpha and dysregulation of the
      microbial-induced inflammatory response in the periodontium.

PMID- 15728181
TI  - Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize
      local responses to mechanical loading in vitro and in vivo.
AB  - Dentin matrix protein 1 (DMP1) is highly expressed in osteocytes and is
      mechanically responsive. To study osteocyte-specific and mechanically regulated
      DMP1 gene expression, the transcriptional activity of three cis-regulatory
      regions was first examined in an osteoblast differentiation model in vitro using
      a green fluorescent protein (GFP) reporter. Expression of the -9624 to +1996 bp
      (10 kb) and -7892 to +4439 bp (8 kb) DMP1 cis-regulatory regions dramatically
      increased in areas of mineralized matrix, in dendritic, osteocyte-like cells.
      Mineralizing cultures expressing the 8-kb construct show dramatic GFP increases
      in response to loading in cells with a dendritic morphology. Transgenic mice
      expressing the 8-kb DMP1-GFP and -2433 to +4439 bp (2.5 kb) DMP1-LacZ were
      generated. Osteocyte-specific expression was found with the 8 kb but not with the
      2.5 kb in postnatal animals. However, the 2.5 kb could support expression in
      rapidly forming osteoblasts and pre-osteocytes in the embryo. Primary calvarial
      osteoblast cultures demonstrated that the 2.5 kb supports weak expression in a
      subset of osteoblasts and pre-osteocytes, but not in mature osteocytes. However,
      the 8 kb supports robust expression in primary bone marrow cultures. Therefore
      the region -7892 to -2433 bp, termed a 5.5-kb "Osteocyte Enhancer Module,"
      appears to be required for osteocyte specificity. Ulnae of mice with the 8-kb
      DMP1-GFP were subjected to mechanical loading where GFP expression increased
      selectively and locally in osteocytes, distal to the mid-shaft and near the
      surface of the bone. Thus, the 8-kb region of the DMP1 gene is a target for
      mechanotransduction in osteocytes, and its cis-regulatory activity may be
      correlated to local strain in bone.

PMID- 15728182
TI  - Regulation of L-type Ca2+ channel activity and insulin secretion by the Rem2
      GTPase.
AB  - Voltage-dependent calcium (Ca2+) channels are involved in many specialized
      cellular functions and are controlled by a diversity of intracellular signals.
      Recently, members of the RGK family of small GTPases (Rem, Rem2, Rad, Gem/Kir)
      have been identified as novel contributors to the regulation of L-type calcium
      channel activity. In this study, microarray analysis of the mouse insulinoma MIN6
      cell line revealed that the transcription of Rem2 gene is strongly induced by
      exposure to high glucose, which was confirmed by real-time reverse transcriptase
      PCR and RNase protection analysis. Because elevation of intracellular Ca2+ in
      pancreatic beta-cells is essential for insulin secretion, we tested the
      hypothesis that Rem2 attenuates Ca2+ currents to regulate insulin secretion. Co
      expression of Rem2 with CaV 1.2 or CaV1.3 L-type Ca + channels in a heterologous
      expression system completely inhibits de novo Ca2+ current expression. In
      addition, ectopic overexpression of Rem2 both inhibited L-type Ca2+ channel
      activity and prevented glucose-stimulated insulin secretion in pancreatic beta
      cell lines. Co-immunoprecipitation studies demonstrate that Rem2 associates with
      a variety of CaVbeta subunits. Importantly, surface biotinylation studies
      demonstrate that the membrane distribution of Ca2+ channels was not reduced at a
      time when channel activity was potently inhibited by Rem2 expression, indicating
      that Rem2 modulates channel function without interfering with membrane
      trafficking. Taken together, these data suggest that inhibition of L-type Ca2+
      channels by Rem2 signaling may represent a new and potentially important
      mechanism for regulating Ca2+-triggered exocytosis in hormone-secreting cells,
      including insulin secretion in pancreatic beta-cells.

PMID- 15728183
TI  - A central kinase domain of type I phosphatidylinositol phosphate kinases is
      sufficient to prime exocytosis: isoform specificity and its underlying mechanism.
AB  - Exocytosis, a critical process for neuronal communication and hormonal
      regulation, involves several distinct steps including MgATP-dependent priming
      (which involves the synthesis of phosphatidylinositol 4,5-bisphosphate). Type I
      phosphatidylinositol phosphate kinases (PIPKIs) were purified biochemically as a
      priming factor. PIPKI consists of three domains: the N-terminal region, the
      central kinase domain, and the C-terminal region. Three isoforms (alpha, beta,
      and gamma) of PIPKI have been identified, and each is alternatively spliced at
      the C-terminal region. In the present study, we conducted a structure/function
      analysis of PIPKIs in the priming of exocytosis, and we found that recombinant
      PIPKIalpha and PIPKIgamma had priming activity. However, an unexpected finding of
      these results was that PIPKIbeta did not prime exocytosis. The N- or C-terminal
      region of PIPKIalpha and PIPKIgamma was not required for priming, which indicates
      that the central kinase domain is sufficient for this process. Alternative
      splicing in each isoform did not affect the isoform specificity in priming.
      Priming activity by isoforms is strongly correlated with their
      phosphatidylinositol phosphate kinase activity because PIPKIalpha and PIPKIgamma
      had higher kinase activity than PIPKIbeta. These results suggest that PIPKIalpha
      and PIPKIgamma are the critical priming factors for exocytosis; it also suggests
      that the levels of phosphatidylinositol phosphate kinase activity in producing
      phosphatidylinositol 4,5-bisphosphate specify the function of PIPKI isoforms in
      priming.

PMID- 15728184
TI  - Crystal structure of hemoglobin protease, a heme binding autotransporter protein
      from pathogenic Escherichia coli.
AB  - The acquisition of iron is essential for the survival of pathogenic bacteria,
      which have consequently evolved a wide variety of uptake systems to extract iron
      and heme from host proteins such as hemoglobin. Hemoglobin protease (Hbp) was
      discovered as a factor involved in the symbiosis of pathogenic Escherichia coli
      and Bacteroides fragilis, which cause intra-abdominal abscesses. Released from E.
      coli, this serine protease autotransporter degrades hemoglobin and delivers heme
      to both bacterial species. The crystal structure of the complete passenger domain
      of Hbp (110 kDa) is presented, which is the first structure from this class of
      serine proteases and the largest parallel beta-helical structure yet solved.

PMID- 15728185
TI  - Sphingosine 1-phosphate-induced mobilization of intracellular Ca2+ mediates rac
      activation and adherens junction assembly in endothelial cells.
AB  - Sphingosine 1-phosphate (S1P) ligation of endothelial differentiation gene-1
      receptor coupled to the heterotrimeric G protein, Gi, promotes endothelial
      barrier strengthening via Rac-dependent assembly of adherens junctions (AJs).
      However, the mechanism of Rac activation induced by S1P stimulation remains
      unclear. In live endothelial cells expressing GFP-Rac, we observed that S1P
      induced the translocation of Rac to intercellular junctions, resulting in
      junctional sealing. We investigated the role of intracellular Ca2+ in signaling
      Rac activation and the enhancement of endothelial barrier function. We observed
      that S1P activated the release of Ca2+ from endoplasmic reticulum stores, and
      subsequent Ca2+ entry via lanthanum-sensitive store-operated Ca2+ channels (SOC)
      after store depletion. Inhibition of Gi, phospholipase C, or inositol
      trisphosphate receptor prevented the S1P-activated increase in intracellular Ca2+
      as well as Rac activation, AJ assembly, and enhancement of endothelial barrier.
      Chelation of intracellular Ca2+ with BAPTA blocked S1P-induced Rac activation,
      indicating the requirement for Ca2+ in the response. Inhibition of SOC by
      lanthanum or transient receptor potential channel 1 (TRPC1), a SOC constituent,
      by TRPC1 antibody, failed to prevent S1P-induced Rac translocation to junctions
      and AJ assembly. Thus, our results demonstrate that S1P promotes endothelial
      junctional integrity by activating the release of endoplasmic reticulum-Ca2+,
      which induces Rac activation and promotes AJ annealing.

PMID- 15728186
TI  - Determination of aberrant O-glycosylation in the IgA1 hinge region by electron
      capture dissociation fourier transform-ion cyclotron resonance mass spectrometry.
AB  - In a number of human diseases of chronic inflammatory or autoimmune character,
      immunoglobulin molecules display aberrant glycosylation patterns of N- or O
      linked glycans. In IgA nephropathy, IgA1 molecules with incompletely
      galactosylated O-linked glycans in the hinge region (HR) are present in mesangial
      immunodeposits and in circulating immune complexes. It is not known whether the
      Gal deficiency in IgA1 proteins occurs randomly or preferentially at specific
      sites. To develop experimental approaches to address this question, the synthetic
      IgA1 hinge region and hinge region from a naturally Gal-deficient IgA1 myeloma
      protein have been analyzed by 9.4 tesla Fourier transform-ion cyclotron resonance
      mass spectrometry. Fourier transform-ion cyclotron resonance mass spectrometry
      offers two complementary fragmentation techniques for analysis of protein
      glycosylation by tandem mass spectrometry. Infrared multiphoton dissociation of
      isolated myeloma IgA1 hinge region peptides confirms the amino acid sequence of
      the de-glycosylated peptide and positively identifies a series of fragments
      differing in O-glycosylation. To localize sites of O-glycan attachment, synthetic
      IgA1 HR glycopeptides and HR from a naturally Gal-deficient polymeric IgA1
      myeloma protein were analyzed by electron capture dissociation and activated ion
      electron capture dissociation. Multiple sites of O-glycan attachment (including
      sites of Gal deficiency) in myeloma IgA1 HR glycoforms were identified (in all
      but one case uniquely). These results represent the first direct identification
      of multiple sites of O-glycan attachment in IgA1 hinge region by mass
      spectrometry, thereby enabling future characterization at the molecular level of
      aberrant glycosylation of IgA1 in diseases such as IgA nephropathy.

PMID- 15728187
TI  - p38 MAPK activation elevates serotonin transport activity via a trafficking
      independent, protein phosphatase 2A-dependent process.
AB  - Presynaptic, plasma membrane serotonin (5-hydroxytryptamine; 5-HT) transporters
      (SERTs) clear 5-HT following vesicular release and are regulated through
      trafficking-dependent pathways. Recently, we provided evidence for a trafficking
      independent mode of SERT regulation downstream of adenosine receptor (AR)
      activation that is sensitive to p38 MAPK inhibitors. Here, we probe this pathway
      in greater detail, demonstrating elevation of 5-HT transport by multiple p38 MAPK
      activators (anisomycin, H(2)O(2), and UV radiation), in parallel with p38 MAPK
      phosphorylation, as well as suppression of anisomycin stimulation by p38 MAPK
      siRNA treatments. Studies with transporter-transfected Chinese hamster ovary
      cells reveal that SERT stimulation is shared with the human norepinephrine
      transporter but not the human dopamine transporter. Saturation kinetic analyses
      of anisomycin-SERT activity reveal a selective reduction in 5-HT K(m) supported
      by a commensurate increase in 5-HT potency (K(i)) for displacing surface
      antagonist binding. Anisomycin treatments that stimulate SERT activity do not
      elevate surface SERT surface density whereas stimulation is lost with preexposure
      of cells to the surface-SERT inactivating reagent, 2-(trimethylammonium)ethyl
      methane thiosulfonate. Guanylyl cyclase (1H-(1,2,4)-oxadiazolo[4,3-a]-quinoxalin
      1-one) and protein kinase G inhibitors (H8, DT-2) block AR stimulation of SERT
      yet fail to antagonize SERT stimulation by anisomycin. We thus place p38 MAPK
      activation downstream of protein kinase G in a SERT-catalytic regulatory pathway,
      distinct from events controlling SERT surface density. In contrast, the activity
      of protein phosphatase 2A inhibitors (fostriecin and calyculin A) to attenuate
      anisomycin stimulation of 5-HT transport suggests that protein phosphatase 2A is
      a critical component of the pathway responsible for p38 MAPK up-regulation of
      SERT catalytic activity.

PMID- 15728188
TI  - A phosphorylation state-specific antibody recognizes Hsp27, a novel substrate of
      protein kinase D.
AB  - The use of phosphorylation state-specific antibodies has revolutionized the field
      of cellular signaling by Ser/Thr protein kinases. A more recent application of
      this technology is the development of phospho-specific antibodies that
      specifically recognize the consensus substrate phosphorylated motif of a given
      protein kinase. Here, we describe the development and use of such an antibody
      which is directed against the optimal phosphorylation motif of protein kinase D
      (PKD). A degenerate phosphopeptide library with fixed residues corresponding to
      the consensus LXR(Q/K/E/M)(M/L/K/E/Q/A)S*XXXX was used as an antigen to generate
      an antibody that recognizes this motif. We characterized the antibody by enzyme
      linked immunosorbent assay and with immobilized peptide arrays and also detected
      immunoreactive phosphoproteins in HeLa cells stimulated with agonists known to
      activate PKD. Silencing PKD expression using RNA interference validated the
      specificity of this antibody immunoreactive against putative substrates. The
      antibody also detected the PKD substrates RIN1 and HDAC5. Knowledge of the PKD
      consensus motif also enabled us to identify Ser(82) in the human heat shock
      protein Hsp27 as a novel substrate for PKD. We term this antibody anti-PKD pMOTIF
      and predict that it will enable the discovery of novel PKD substrate proteins in
      cells.

PMID- 15728189
TI  - Crystal structure of CC3 (TIP30): implications for its role as a tumor
      suppressor.
AB  - CC3 (TIP30) is a protein with pro-apoptotic and anti-metastatic properties. The
      tumor suppressor effect of CC3 has been suggested to result from inhibition of
      nuclear transport by binding to importin betas or by regulating transcription
      through interaction in a complex with co-activator independent of AF-2 function
      (CIA) and the c-myc gene. Previous biochemical studies indicated that CC3 has
      protein kinase activity, and a structural similarity to cAMP-dependent protein
      kinase catalytic subunit was proposed. By contrast, bioinformatics studies
      suggested a relationship of CC3 to the short chain dehydrogenase reductase
      family. To clarify details of the CC3 structural family and ligand binding
      properties, we have determined the crystal structure of CC3 at 1.7-A resolution.
      CC3 has a short chain dehydrogenase reductase fold and binding specificity for
      NADPH, yet it is unlikely to be normally enzymatically active because it is
      monomeric. These structural results, in conjunction with data from earlier
      mutagenesis work on the nucleotide binding motif, suggest that NADPH binding is
      important for the biological activity of CC3, including interaction with
      importins and with the CIA/c-myc system. CC3 provides an example of the
      adaptation of a metabolic enzyme fold to include a regulatory role, as also seen
      in the case of the NADH-binding co-repressor CtBP.

PMID- 15728190
TI  - A Sec14p-nodulin domain phosphatidylinositol transfer protein polarizes membrane
      growth of Arabidopsis thaliana root hairs.
AB  - Phosphatidylinositol (PtdIns) transfer proteins (PITPs) regulate signaling
      interfaces between lipid metabolism and membrane trafficking. Herein, we
      demonstrate that AtSfh1p, a member of a large and uncharacterized Arabidopsis
      thaliana Sec14p-nodulin domain family, is a PITP that regulates a specific stage
      in root hair development. AtSfh1p localizes along the root hair plasma membrane
      and is enriched in discrete plasma membrane domains and in the root hair tip
      cytoplasm. This localization pattern recapitulates that visualized for
      PtdIns(4,5)P2 in developing root hairs. Gene ablation experiments show AtSfh1p
      nullizygosity compromises polarized root hair expansion in a manner that
      coincides with loss of tip-directed PtdIns(4,5)P2, dispersal of secretory
      vesicles from the tip cytoplasm, loss of the tip f-actin network, and manifest
      disorganization of the root hair microtubule cytoskeleton. Derangement of tip
      directed Ca2+ gradients is also apparent and results from isotropic influx of
      Ca2+ from the extracellular milieu. We propose AtSfh1p regulates intracellular
      and plasma membrane phosphoinositide polarity landmarks that focus membrane
      trafficking, Ca2+ signaling, and cytoskeleton functions to the growing root hair
      apex. We further suggest that Sec14p-nodulin domain proteins represent a family
      of regulators of polarized membrane growth in plants.

PMID- 15728191
TI  - The LIM protein Ajuba influences p130Cas localization and Rac1 activity during
      cell migration.
AB  - Cell migration requires extension of lamellipodia that are stabilized by
      formation of adhesive complexes at the leading edge. Both processes are regulated
      by signaling proteins recruited to nascent adhesive sites that lead to activation
      of Rho GTPases. The Ajuba/Zyxin family of LIM proteins are components of cellular
      adhesive complexes. We show that cells from Ajuba null mice are inhibited in
      their migration, without associated abnormality in adhesion to extracellular
      matrix proteins, cell spreading, or integrin activation. Lamellipodia production,
      or function, is defective and there is a selective reduction in the level and
      tyrosine phosphorylation of FAK, p130Cas, Crk, and Dock180 at nascent focal
      complexes. In response to migratory cues Rac activation is blunted in Ajuba null
      cells, as detected biochemically and by FRET analysis. Ajuba associates with the
      focal adhesion-targeting domain of p130Cas, and rescue experiments suggest that
      Ajuba acts upstream of p130Cas to localize p130Cas to nascent adhesive sites in
      migrating cells thereby leading to the activation of Rac.

PMID- 15728192
TI  - Role of cytoplasmic dynein in the axonal transport of microtubules and
      neurofilaments.
AB  - Recent studies have shown that the transport of microtubules (MTs) and
      neurofilaments (NFs) within the axon is rapid, infrequent, asynchronous, and
      bidirectional. Here, we used RNA interference to investigate the role of
      cytoplasmic dynein in powering these transport events. To reveal transport of MTs
      and NFs, we expressed EGFP-tagged tubulin or NF proteins in cultured rat
      sympathetic neurons and performed live-cell imaging of the fluorescent
      cytoskeletal elements in photobleached regions of the axon. The occurrence of
      anterograde MT and retrograde NF movements was significantly diminished in
      neurons that had been depleted of dynein heavy chain, whereas the occurrence of
      retrograde MT and anterograde NF movements was unaffected. These results support
      a cargo model for NF transport and a sliding filament model for MT transport.

PMID- 15728194
TI  - Bcl-X(L) specifically activates Bak to induce swelling and restructuring of the
      endoplasmic reticulum.
AB  - Bcl-2 family members Bak and Bax constitute a mitochondrial gateway for multiple
      death pathways. Both proteins are also present in the endoplasmic reticulum where
      they control apoptosis through the regulation of calcium levels. We show here
      that reticular Bak has the additional capacity of modulating the structure of
      this organelle. Coexpression of Bak and Bcl-X(L) provokes extensive swelling and
      vacuolization of reticular cisternae. A Bak version lacking the BH3 domain
      suffices to induce this phenotype, and reticular targeting of this mutant retains
      the activity. Expression of upstream BH3-only activators in similar conditions
      recapitulates ER swelling and vacuolization if ryanodine receptor calcium channel
      activity is inhibited. Experiments with Bak and Bax-deficient mouse embryonic
      fibroblasts show that endogenous Bak mediates the effect, whereas Bax is mainly
      irrelevant. These results reveal a previously unidentified role of Bak in
      regulating reticular conformation. Because this activity is absent in Bax, it
      constitutes one of the first examples of functional divergence between the two
      multidomain homologues.

PMID- 15728193
TI  - Molecular dissection of the photoreceptor ribbon synapse: physical interaction of
      Bassoon and RIBEYE is essential for the assembly of the ribbon complex.
AB  - The ribbon complex of retinal photoreceptor synapses represents a specialization
      of the cytomatrix at the active zone (CAZ) present at conventional synapses. In
      mice deficient for the CAZ protein Bassoon, ribbons are not anchored to the
      presynaptic membrane but float freely in the cytoplasm. Exploiting this
      phenotype, we dissected the molecular structure of the photoreceptor ribbon
      complex. Identifiable CAZ proteins segregate into two compartments at the ribbon:
      a ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and
      the motor protein KIF3A, and an active zone compartment including RIM2, Munc13-1,
      a Ca2+ channel alpha1 subunit, and ERC2/CAST1. A direct interaction between the
      ribbon-specific protein RIBEYE and Bassoon seems to link the two compartments and
      is responsible for the physical integrity of the photoreceptor ribbon complex.
      Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses,
      suggesting a novel role for the CtBP/BARS family in the molecular assembly and
      function of central nervous system synapses.

PMID- 15728196
TI  - Clinical review: Current concepts in the management of unilateral recurrent
      laryngeal nerve paralysis after thyroid surgery.
AB  - OBJECTIVE: This study was designed to provide an update on the pathophysiological
      concepts and patient management in a common complication of thyroid surgery,
      unilateral recurrent laryngeal nerve paralysis (URLNP). METHOD: Recent
      publications in physiology and head and neck surgery were reviewed. RESULTS: Even
      for experienced surgeons, URLNP may occur after thyroid surgery, especially for
      thyroid cancer and in case of reoperation. URLNP is frequently well tolerated but
      may be life threatening by inducing aspiration pneumonia. Permanent URLNP may
      decrease quality of life by decreasing voice quality and increasing vocal effort.
      Spontaneous recovery of vocal function, with or without full recovery of vocal
      fold motion, may occur due to spontaneous axonal regrowth or other neurological
      phenomena. In the last decade, several surgical techniques have been developed to
      treat aspiration and poor voice quality due to URLNP by medialization of the
      paralyzed vocal fold. These techniques are simple, have a low complication rate,
      and are highly efficient in eliminating aspiration and improving voice quality
      and quality of life. CONCLUSIONS: The voice and swallowing handicap caused by
      URLNP may be efficiently treated by safe and simple techniques. The possibility
      to improve the quality of life should be proposed to all patients with
      symptomatic URLNP.

PMID- 15728197
TI  - Genetic and environmental effects on fasting and postchallenge plasma glucose and
      serum insulin values in Finnish twins.
AB  - The aim of this study was to evaluate genetic and environmental effects on plasma
      glucose, insulin secretion, and resistance in Finnish twins. Altogether 151
      randomly selected twin pairs were examined by the oral glucose tolerance test; 66
      twin pairs were monozygotic and 85 like-sexed dizygotic. We estimated the
      intraclass correlation coefficients and variance components of genetic and
      environmental effects on waist circumference, plasma glucose, and serum insulin.
      For fasting insulin, the proportion of total variation accounted for by additive
      genetic effects (A) and nonshared environmental effects (E) were 43 and 57%,
      respectively. As to postchallenge insulin and waist circumference, A effects were
      stronger in female twins (51 and 70%, respectively) than male twins in whom no
      significant evidence for genetic variance was found. Of the variation in fasting
      glucose, A and E effects accounted for 45 and 55%, respectively. Of the variation
      in postchallenge glucose, E effects had a greater role (65%), compared with A
      effects (35%); A effects on pre- and postchallenge insulin levels were highly
      correlated (genetic correlation coefficient = 0.81). In conclusion, additive
      genetic effects are important for the insulin secretion, whereas nonshared
      environmental effects contribute strongly to peripheral insulin resistance.

PMID- 15728195
TI  - Cog3p depletion blocks vesicle-mediated Golgi retrograde trafficking in HeLa
      cells.
AB  - The conserved oligomeric Golgi (COG) complex is an evolutionarily conserved multi
      subunit protein complex that regulates membrane trafficking in eukaryotic cells.
      In this work we used short interfering RNA strategy to achieve an efficient
      knockdown (KD) of Cog3p in HeLa cells. For the first time, we have demonstrated
      that Cog3p depletion is accompanied by reduction in Cog1, 2, and 4 protein levels
      and by accumulation of COG complex-dependent (CCD) vesicles carrying v-SNAREs
      GS15 and GS28 and cis-Golgi glycoprotein GPP130. Some of these CCD vesicles
      appeared to be vesicular coat complex I (COPI) coated. A prolonged block in CCD
      vesicles tethering is accompanied by extensive fragmentation of the Golgi ribbon.
      Fragmented Golgi membranes maintained their juxtanuclear localization, cisternal
      organization and are competent for the anterograde trafficking of vesicular
      stomatitis virus G protein to the plasma membrane. In a contrast, Cog3p KD
      resulted in inhibition of retrograde trafficking of the Shiga toxin. Furthermore,
      the mammalian COG complex physically interacts with GS28 and COPI and
      specifically binds to isolated CCD vesicles.

PMID- 15728198
TI  - A window of opportunity: the diagnosis of gonadotropin deficiency in the male
      infant.
AB  - A common cause of micropenis is congenital hypogonadotropic hypogonadism, whether
      isolated or associated with multiple pituitary hormone deficiencies. The
      postnatal surge in FSH, LH, and testosterone in the male infant as a consequence
      of the continued function of the fetal GnRH pulse generator provides a 6-month
      window of opportunity to establish the diagnosis of hypogonadotropic hypogonadism
      and alert the clinician to the possibility of its association with multiple
      pituitary hormone deficiencies. When ACTH or GH deficiency or both deficiencies
      are present, hypoglycemia and cortisol deficiency can lead to neonatal and
      infantile death or increased morbidity. Establishing the diagnosis of
      hypogonadotropic hypogonadism in infancy preempts the uncertainties and delays in
      distinguishing constitutional delay in puberty from hypogonadotropic
      hypogonadism. Accordingly, hormone replacement therapy can be initiated at the
      normal age of pubertal onset. The ontogenesis of infantile testicular function,
      including the possible significance of the infantile surge in gonadotropins and
      testosterone, is reviewed. The molecular basis for certain developmental
      disorders associated with hypogonadotropic hypogonadism and micropenis is
      considered and the management and treatment of congenital hypopituitarism
      discussed.

PMID- 15728199
TI  - GCMB mutation in familial isolated hypoparathyroidism with residual secretion of
      parathyroid hormone.
AB  - Isolated hypoparathyroidism is an uncommon metabolic disorder characterized by
      hypocalcemia and hyperphosphatemia, with absent or low levels of PTH. It may
      present as an apparently sporadic disorder or may be transmitted in families as a
      genetic trait. Mutations of the calcium-sensing receptor gene and of the
      preproPTH gene have been reported in occasional cases, and a mutation of the
      parathyroid-specific transcription factor GCMB gene has been reported in one
      familial case. We report a second family with isolated hypoparathyroidism and a
      GCMB mutation. The patients were two siblings from asymptomatic, first-cousin
      parents, indicating autosomal recessive inheritance. The mutation consisted of
      the substitution of a glycine residue with a serine at position 63 (G63S) in the
      DNA-binding GCM domain of GCMB. Functional studies in transfected cells showed
      that the mutation caused loss of GCMB function, as it abolished transactivation
      capacity, despite normal subcellular localization, protein stability, and DNA
      binding specificity. Contrary to the previously reported family, our patients
      displayed low but clearly detectable levels of PTH in plasma. This residual
      hormone secretion probably results from a very small residual activity of the
      G63S mutant GCMB.

PMID- 15728200
TI  - Progesterone inhibition of the hypothalamic gonadotropin-releasing hormone pulse
      generator: evidence for varied effects in hyperandrogenemic adolescent girls.
AB  - Compared with normal women, adults with polycystic ovarian syndrome (PCOS)
      require higher progesterone (P) concentrations to inhibit GnRH (LH) pulse
      frequency, which contributes to persistently rapid GnRH pulses and elevated LH
      levels in PCOS. To explore the origin of this abnormality, we assessed
      hypothalamic sensitivity to P feedback in nine normal controls and 11
      hyperandrogenemic (HA) adolescents. Subjects first underwent frequent blood
      sampling for 11 h to assess baseline LH pulse frequency. Thereafter, oral
      estradiol and micronized P were given for 7 d to achieve mean estradiol and P
      levels of 143 +/- 16 pg/ml (524 +/- 60 pmol/liter) and 7.8 +/- 0.7 ng/ml (24.9 +/
      2.3 nmol/liter), respectively. LH pulse frequency was then reassessed. On d 7,
      the slope of the percent reduction of LH pulses per 11 h as a function of the d 7
      P concentration was less in the HA group compared with controls (P = 0.02)
      despite similar P levels. LH pulse frequency was suppressed in all NC (mean, 7.0
      to 3.4 pulses/11 h), but was unchanged in six of the HA girls (mean, 8.3 to 7.5
      pulses/11 h). In contrast, in the other five HA adolescents, P induced similar
      slowing of LH pulses to that seen in NC (mean, 10.0 to 5.0 pulses/11 h). Baseline
      free testosterone levels were similar in both HA groups; the only observed
      difference between these HA groups is that the P-suppressible subjects were all
      of Hispanic descent. These data suggest that hyperandrogenemia during adolescence
      is variably associated with decreased sensitivity to P, which may have a
      partially genetic basis.

PMID- 15728201
TI  - Sexual dimorphism of thyroid function in newborns with congenital hypothyroidism.
AB  - Several characteristics of congenital hypothyroidism (CH) from thyroid dysgenesis
      (ectopy and athyreosis) are sexually dimorphic: girls are more often affected,
      and boys are twice more likely than girls to have absent knee epiphysis at
      diagnosis, an indicator of severity of CH. Whether the biochemical severity of CH
      is sexually dimorphic is unknown. We therefore reviewed the charts of all
      newborns referred to our clinic from 1990 to 2004 because of a TSH greater than
      15 mU/liter on newborn screening. In ectopy (24 boys, 78 girls) at screening,
      median TSH was lower in boys than girls (75 vs. 135 mU/liter, P = 0.017), whereas
      total T4 was higher (123 vs. 68 mmol/liter, P = 0.003); the same differences were
      present at diagnosis: TSH was 90 and 284 mU/liter (P = 0.001) and free T4 10 and
      7 pmol/liter (P = 0.049) in boys and girls, respectively. The log-linear
      relationships between TSH and T4 at screening and diagnosis were similar in both
      sexes. In athyreosis (10 boys, 14 girls) at screening and diagnosis, TSH was
      higher in boys [308 vs. 207 (P = 0.053) and 712 vs. 555 mU/liter (P = 0.0057)].
      In infants with an orthotopic gland (dyshormonogenesis, nine boys, 13 girls),
      there was no sex difference in biochemical severity of CH. In conclusion, sexual
      dimorphism in biochemical severity of CH from thyroid dysgenesis is apparent but
      differs according to etiology. These novel findings suggest that sexual
      dimorphism should be considered as a modulator of the mechanisms underlying the
      fate and function of ectopic thyroid cells.

PMID- 15728202
TI  - Differential regulation of synthetic glucocorticoids on gene expression levels of
      glucocorticoid-induced leucine zipper and interleukin-2.
AB  - Individual glucocorticoid (GC) sensitivity was determined by measuring the
      effects of several clinically used GCs on transactivation of the GC-induced
      leucine zipper (GILZ) gene and on transrepression of the IL-2 gene using
      quantitative real-time PCR. A clear difference in relative potencies for
      transactivation and transrepression of the various GCs was observed, suggesting
      differential effects. To determine whether the in vitro outcomes could predict in
      vivo effects of GCs, 15 individuals underwent a 0.25-mg dexamethasone (DEX)
      suppression test (DST) while determining GILZ and IL-2 mRNA levels in their
      peripheral blood mononuclear cells incubated with hydrocortisone, DEX,
      budesonide, and prednisolone. No correlations were found between the DST and the
      two expression assays. However, significant correlations existed between
      hydrocortisone and DEX (r = 0.52; P = 0.046), hydrocortisone and budesonide (r =
      0.48; P = 0.069), and hydrocortisone and prednisolone (r = 0.86; P = 0.007)
      regarding GILZ mRNA levels, and between hydrocortisone and DEX (r = 0.62; P =
      0.014), hydrocortisone and budesonide (r = 0.71; P = 0.003), and hydrocortisone
      and prednisolone (r = 0.71; P = 0.047) regarding IL-2 mRNA levels. In conclusion,
      intra- and inter-individual variations in GC sensitivity were observed using two
      expression assays representing GC-mediated transactivation and transrepression.
      The two expression assays did not correlate with each other or with the results
      of the DST. This suggests that regulation of the hypothalamic-pituitary-adrenal
      axis is more complex. However, within an individual person, these two tests
      combined might predict what type and dosage of GC will be preferable in
      individual patients for its inhibitory clinical effects, together with relatively
      fewer transactivating effects related to adverse effects.

PMID- 15728203
TI  - Phenotypic variation in hyperandrogenic women influences the findings of abnormal
      metabolic and cardiovascular risk parameters.
AB  - In hyperandrogenic women, several phenotypes may be observed. This includes women
      with classic polycystic ovary syndrome (C-PCOS), those with ovulatory (OV) PCOS,
      and women with idiopathic hyperandrogenism (IHA), which occurs in women with
      normal ovaries. Where other causes have been excluded, we categorized 290
      hyperandrogenic women who were seen consecutively for this complaint between 1993
      and 2004 into these three subgroups. The aim was to compare the prevalence of
      obesity, insulin resistance, and dyslipidemia as well as increases in C-reactive
      protein and homocysteine in these different phenotypes with age-matched ovulatory
      controls of normal weight (n = 85) and others matched for body mass index (BMI)
      with women with C-PCOS (n = 42). Although BMI affected fasting serum insulin and
      the Quantitative Insulin-Sensitivity Check Index, these markers of insulin
      resistance were greatest in C-PCOS (n = 204), followed by OV-PCOS (n = 50) and
      then IHA (n = 33). Androgen levels were similar in OV-PCOS and IHA but were
      higher in C-PCOS, whereas gonadotropins were similar in all groups. Lipid
      abnormalities were highest in C-PCOS and OV-PCOS and were normal in IHA. C
      reactive protein was elevated in C-PCOS and OV-PCOS but not IHA. Homocysteine was
      elevated only in C-PCOS. Overall, the prevalence of obesity (BMI > 30) was 29% in
      C-PCOS, 8% in OV-PCOS, and 15% in IHA and insulin resistance (Quantitative
      Insulin-Sensitivity Check Index < 0.33) was 68% in C-PCOS, 36% in OV-PCOS, and
      26% in IHA. The prevalence of having at least one elevated cardiovascular risk
      marker was 45% in C-PCOS 38% in OV-PCOS and was not increased on IHA (6%). These
      results suggest that among hyperandrogenic women the prevalence of abnormal
      metabolic and cardiovascular risk parameters is greatest in C-PCOS, followed by
      OV-PCOS and then women with IHA. Moreover, in that in OV-PCOS and IHA, ages and
      weights were similar yet the prevalence of metabolic and cardiovascular risk was
      greater in OV-PCOS, the finding of polycystic ovaries may be a significant
      modifying factor.

PMID- 15728204
TI  - The functional Thr130Ile and Val255Met polymorphisms of the hepatocyte nuclear
      factor-4alpha (HNF4A): gene associations with type 2 diabetes or altered beta
      cell function among Danes.
AB  - HNF4A encodes an orphan nuclear receptor that plays crucial roles in regulating
      hepatic gluconeogenesis and insulin secretion. The aim of the present study was
      to examine two rare missense polymorphisms of HNF4A, Thr130Ile and Val255Met, for
      altered function and for association with type 2 diabetes (T2D). We have examined
      these polymorphisms 1) by in vitro transactivation studies and 2) by genotyping
      the variants in 1409 T2D patients and in 4726 glucose-tolerant Danish white
      subjects. When tested in COS7 cells, both the Thr130Ile and the Val255Met
      variants showed a significant decrease in transactivation activity compared with
      wild-type (73% of wild-type, P = 0.02, and 76%, P = 0.04, respectively). The
      Thr130Ile variant had a significantly increased carrier frequency among T2D
      patients compared with glucose-tolerant subjects [odds ratio, 1.26 (1.01-1.57); P
      = 0.04]. The rare Val255Met polymorphism had a similar frequency among T2D
      patients and glucose-tolerant subjects. Heterozygous glucose-tolerant carriers of
      the variant showed, however, decreased levels of fasting serum C-peptide (76%; P
      = 0.03) and decreased fasting serum triglyceride (58%; P = 0.02). In conclusion,
      The Thr130Ile and the Val255Met polymorphisms decrease the transcriptional
      activity of HNF4A, and the Thr130Ile polymorphism associates with T2D, whereas
      the Val255Met variant associates with a decrease in fasting serum C-peptide.

PMID- 15728205
TI  - In vitro coexpression and pharmacological rescue of mutant gonadotropin-releasing
      hormone receptors causing hypogonadotropic hypogonadism in humans expressing
      compound heterozygous alleles.
AB  - We analyzed the function of mutant GnRH receptor (GnRHR) pairs associated with
      compound heterozygous patients showing complete or partial forms of
      hypogonadotropic hypogonadism. We did this to examine potential interactions
      between misfolded mutants that may influence net receptor function and response
      to pharmacological rescue. Nine pairs of GnRHR mutants and an unreported
      combination (L314X((stop))/R262Q) were studied. Coexpression of each pair of
      mutants in COS-7 cells resulted in an active predominant effect (Q106R/L266R,
      A171T/Q106R, T32I/C200Y, and R262Q/A129D mutant GnRHR pairs), an additive effect
      (R262Q/Q106R, N10K/Q106R, and R262Q/Y284C human GnRHR pairs), or a dominant
      negative effect (L314X((stop))/Q106R, Q106R+S217R/R262Q, and L314X((stop))/R262Q
      GnRHRs). For all combinations, addition of the pharmacoperone IN3 increased both
      agonist binding and effector coupling. The IN3 response was unpredictable because
      responses could be either similar, higher, or lower, compared with that exhibited
      by the less affected mutant. The clinical phenotype in patients expressing
      complex heterozygous alleles appears to be dictated by both the contribution from
      each mutant and a dominant-negative effect similar to that reported for mutants
      and wild-type receptor. Depending on the genotype, partial or full restoration of
      receptor function in response to pharmacological chaperones may be achievable
      goals in patients bearing inactivating mutations in the GnRHR gene.

PMID- 15728206
TI  - The dynamics of growth hormone (GH) secretion in adult cancer survivors with
      severe GH deficiency acquired after brain irradiation in childhood for
      nonpituitary brain tumors: evidence for preserved pulsatility and diurnal
      variation with increased secretory disorderliness.
AB  - Dynamics of GH secretion in patients with GH deficiency due to radiation damage
      of the hypothalamic-pituitary (h-p) axis acquired in childhood has rarely been
      studied. Thus, we used a sensitive chemiluminescence GH assay to analyze 24-h GH
      profiles (20-min sampling) from 10 adult cancer survivors with severe GH
      deficiency acquired after brain irradiation in childhood for nonpituitary brain
      tumors. An age- and sex-matched control group of 30 normal healthy volunteers,
      eight of whom were matched for body mass index with the patients, were also
      studied. Cluster analysis with gender-specific comparisons revealed a significant
      reduction (P < 0.05) in all amplitude-related measurements [profile mean GH
      levels or area under curve for GH, absolute (maximum) GH peak height, mean peak
      height, and mean pulse area] in patients. No differences were observed in
      frequency-related measurements (pulse frequency, pulse duration, and interpulse
      interval). Pulsatile secretion was relatively more attenuated than basal
      secretion in patients, and approximate entropy (ApEn) scores were significantly
      (P < 0.05) elevated, suggesting more disordered GH secretion. Radiation inflicts
      quantitative damage to the h-p axis, leading to amplitude-dependent dampening of
      GH secretion with relative preservation of nonpulsatile secretion. Qualitative
      perturbation in hypothalamic control of GH release is evident by the increase in
      ApEn values reflecting more disordered GH secretion. The integrity of the h-p
      axis and GH neuroregulation is fundamentally preserved in irradiated GH-deficient
      patients with a GH secretory pattern similar to that observed in normal subjects
      and those with GH deficiency due to other etiologies.

PMID- 15728207
TI  - Early menarche and the development of cardiovascular disease risk factors in
      adolescent girls: the Fels Longitudinal Study.
AB  - The purpose of this study was to evaluate the influence of menarcheal age on
      changes in insulin, glucose, lipids, and blood pressure during adolescence and to
      assess whether body composition modifies this relationship. We examined 391
      girls, a subset of Fels Longitudinal Study female participants (8-21 yr of age).
      Self-reported menarcheal age was classified based on the National Health and
      Nutrition Examination Survey III distribution, in which early menarche was at the
      25th percentile or less (11.9 yr). Age at menarche was examined in relation to
      measures of body composition [e.g. fat-free mass (FFM) and percent body fat
      (PBF)], insulin resistance, blood pressure, and lipid profile. The effects of
      menarcheal age and body composition on cardiovascular disease risk factor changes
      were analyzed with serial data mixed models. Median menarcheal age was 12.7 yr
      (range, 9.8-17.0 yr), with 91 girls (23%) classified as early menarche. Girls
      with early menarche had more deleterious changes in insulin, glucose, blood
      pressure, FFM, and PBF levels than girls with average or late menarche.
      Menarcheal age adversely affected cardiovascular disease risk factor changes
      independent of age and changes in FFM or PBF. Girls with early menarche exhibited
      elevated blood pressure and glucose intolerance compared with later maturing
      girls, independent of body composition.

PMID- 15728208
TI  - Adipokine dysregulation in turner syndrome: comparison of circulating interleukin
      6 and leptin concentrations with measures of adiposity and C-reactive protein.
AB  - Women with Turner syndrome (TS) have increased risks of atherosclerosis, diabetes
      mellitus, and obesity. We hypothesized that women with TS have adverse metabolic
      or inflammatory markers for cardiovascular disease compared with normal women and
      estrogen-deficient controls. This was a cross-sectional study conducted at
      University College London Hospitals, UK. One hundred seventeen estrogen-treated
      women with TS and normal fasting blood glucose were compared with 30 age-matched
      normal controls and 31 estrogen-treated women with 46,XX premature ovarian
      failure (POF). The main outcome measures were markers of the metabolic syndrome,
      including the adipokines IL-6 and leptin, and C-reactive protein (CRP). TS women
      were more obese than controls (waist circumference, 79.9 +/- 12.4, 73.5 +/- 6.9,
      and 74.7 +/- 8.6 cm in TS, normal subjects, and POF controls, respectively; P =
      0.005; body mass index, 26.8 +/- 5.8, 23.7 +/- 3.2, and 22.9 +/- 3.4 kg/m2; P <
      0.001). This obesity was associated with increased CRP (2.9 +/- 1.5, 0.8 +/- 1.0,
      and 1.2 +/- 0.9 mg/liter; P < 0.001) and IL-6 concentrations (1.5 +/- 0.7, 1.0 +/
      1.5, and 1.2 +/- 0.5 pg/ml; P = 0.014), but lower fasting serum insulin (4.7 +/-
      2.3, 6.3 +/- 3.0, and 6.9 +/- 2.9 mIU/ml; P = 0.004), glucose (83 +/- 11, 90 +/-
      7, and 90 +/- 7 mg/dl; P < 0.001), and leptin (10.2 +/- 6.3, 14.4 +/- 7.6, and
      14.8 +/- 8.1 ng/ml; P = 0.048). Triglyceride concentrations were similar in TS
      and POF women and were greater than in normal controls (97 +/- 53, 97 +/- 53, and
      71 +/- 27 mg/dl; P = 0.024). We conclude that women with TS have various physical
      and biochemical features suggestive of the metabolic/insulin resistance syndrome,
      but there is a discrepancy among CRP, IL-6, and leptin, with leptin and fasting
      insulin concentrations being lower than expected for the degree of obesity.
      Obesity and estrogen therapy do not fully explain these findings. Women with TS
      may have specific metabolic defects contributing to cardiovascular risk.

PMID- 15728209
TI  - Syndecan-1 is involved in osteoprotegerin-induced chemotaxis in human peripheral
      blood monocytes.
AB  - Chronic inflammation is characterized by tissue infiltration with
      monocytes/macrophages, which possess broad proinflammatory, destructive, and
      remodeling capacities. Elevated levels of osteoprotegerin, an important regulator
      of differentiation and activation of osteoclasts that also affects different
      cells of the immune system, were found in the serum of patients with chronic
      inflammatory diseases. The study of whether osteoprotegerin affects monocyte
      locomotion in vitro and the possible mechanisms and pathways involved was
      investigated using Boyden microchemotaxis chambers and Western blot analyses.
      Osteoprotegerin significantly stimulated monocyte chemotaxis, whereas
      preincubation of monocytes with osteoprotegerin inhibited monocyte migration
      toward optimal concentrations of regulated upon activation normal T cell
      expressed and secreted, monocyte chemotactic protein -1, and procalcitonin. The
      effects of osteoprotegerin were abolished by pretreating cells with heparinase I
      and chondroitinase or antibodies against the ectodomain of syndecan-1.
      Osteoprotegerin signaling was shown to involve protein kinase C,
      phosphatidylinositol 3-kinase/Akt, and tyrosine kinase. Data suggest that
      osteoprotegerin affects monocyte mi-gration and protein kinase C and
      phosphatidylinositol 3-kinase/Akt activation via syndecan-1. Osteoprotegerin
      induced deactivation of monocyte chemotaxis toward different chemokines is due to
      interaction of osteoprotegerin with heparan sulfate and chondroitin sulfate.

PMID- 15728211
TI  - Arterial stiffness is related to insulin resistance in nondiabetic hypertensive
      older adults.
AB  - Hypertension, diabetes, obesity, and aging are associated with increased arterial
      stiffness. Both insulin resistance and hyperglycemia may contribute to the
      development of arterial stiffness. Older nondiabetic hypertensive adults were
      recruited to test the following hypotheses: (1) insulin resistance is associated
      with arterial stiffness, and (2) this relationship is independent of glucose
      tolerance status. Aortic pulse wave velocity (PWV), pulse pressure (PP), insulin
      sensitivity index (S(I), measured by insulin-assisted frequently sampled iv
      glucose test), glucose tolerance status, and abdominal fat mass were assessed in
      37 older (23 male, 14 female, mean age 69.4 +/- 5.9 yr), nondiabetic,
      hypertensive adults after a 4-wk antihypertensive medication withdrawal. Both PWV
      and PP were negatively correlated with S(I) (r = -0.49, P = 0.002, and r = -0.38,
      P = 0.02, respectively). The mean PWV and PP in those with normal glucose
      tolerance were not significantly different from those with impaired glucose
      tolerance (9.8 +/- 2.4 vs. 10.0 +/- 3.1 m/sec, P = 0.79 and 71 +/- 17 vs. 72 +/-
      18 mm Hg, P = 0.80, respectively). In multiple regression analysis, PWV and PP
      remained independently correlated with S(I) (P < 0.05) after adjusting for age,
      gender, fasting glucose, glucose tolerance status, body mass index, or abdominal
      fat mass. These results suggest that in hypertensive, nondiabetic, older adults,
      insulin resistance is associated with arterial stiffness independent of glucose
      tolerance status.

PMID- 15728210
TI  - Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal
      women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.
AB  - BACKGROUND: Strontium ranelate, a new oral drug shown to reduce vertebral
      fracture risk in postmenopausal women with osteoporosis, was studied in the
      Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and
      safety in preventing nonvertebral fractures also. METHODS: Strontium ranelate (2
      g/d) or placebo were randomly allocated to 5091 postmenopausal women with
      osteoporosis in a double-blind placebo-controlled 5-yr study with a main
      statistical analysis over 3 yr of treatment. FINDINGS: In the entire sample,
      relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04),
      and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and
      sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in
      comparison with the placebo group. Among women at high risk of hip fracture (age
      > or = 74 yr and femoral neck bone mineral density T score < or = -3,
      corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction
      for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by
      39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the
      subgroup without prevalent vertebral fracture. Strontium ranelate increased bone
      mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2%
      (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was
      similar in both groups. CONCLUSION: This study shows that strontium ranelate
      significantly reduces the risk of all nonvertebral and in a high-risk subgroup,
      hip fractures over a 3-yr period, and is well tolerated. It confirms that
      strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe
      and effective means of reducing the risk of fracture associated with
      osteoporosis.

PMID- 15728212
TI  - Ghrelin suppression in overweight children: a manifestation of insulin
      resistance?
AB  - Ghrelin levels increase before and decrease after meals, potentially playing a
      role in meal initiation and satiety in an inverse pattern to that of insulin. The
      role of ghrelin in childhood obesity, a state associated with hyperinsulinism and
      insulin resistance, is not fully understood. Therefore, the aims of the present
      study were to investigate the dynamics of ghrelin suppression after an oral
      glucose tolerance test (OGTT) in normal weight (NW) vs overweight (OW) children
      and the relationship of ghrelin suppression to insulin sensitivity. Thirty-seven
      NW (15 males and 22 females; 9.4 +/- 0.2 yr old) and 23 OW (13 males and 10
      females; 9.4 +/- 0.3 yr old) prepubertal children underwent a 3-h OGTT with
      measurements of ghrelin, glucose, and insulin. The fasting glucose to insulin
      ratio and the whole body insulin sensitivity index were used to assess the
      relationship of insulin sensitivity to fasting ghrelin and ghrelin response to
      the OGTT, respectively. Fasting ghrelin levels were significantly lower in OW vs
      NW youth and were mainly influenced by insulin sensitivity independent of
      adiposity. OGTT-induced absolute suppression in ghrelin was approximately 50%
      less in OW vs NW children, resulting in a similar percent suppression from
      baseline in the two groups despite a significantly higher insulin response in OW.
      The suppression of ghrelin correlated positively with the whole body insulin
      sensitivity index (r = 0.43; P = 0.001) and negatively with the change in insulin
      at 30 min (r = -0.31; P = 0.02). Fasting ghrelin, the change in insulin, and the
      change in glucose during the OGTT were the significant independent variables
      contributing to the variance in absolute suppression of ghrelin (r2 = 0.42; P <
      0.001). Only the change in glucose contributed significantly to the variance in
      the percent suppression of ghrelin (r2 = 0.14; P = 0.019). Fasting ghrelin and
      ghrelin suppression after OGTT are modulated by insulin sensitivity. Alterations
      in ghrelin suppression in OW children may be yet another manifestation of the
      insulin resistance of obesity. Whether this is responsible for differences in
      satiety in OW individuals merits additional investigation.

PMID- 15728213
TI  - Hip fracture in women without osteoporosis.
AB  - The proportion of fractures that occur in women without osteoporosis has not been
      fully described, and the characteristics of nonosteoporotic women who fracture
      are not well understood. We measured total hip bone mineral density (BMD) and
      baseline characteristics including physical activity, falls, and strength for
      8065 women aged 65 yr or older participating in the Study of Osteoporotic
      Fractures and then followed these women for hip fracture for up to 5 yr after BMD
      measurement. Among all participants, 17% had osteoporosis (total hip BMD T-score
      < or = -2.5). Of the 243 women with incident hip fracture, 54% were not
      osteoporotic at start of follow-up. Nonosteoporotic women who fractured were less
      likely than osteoporotic women with fracture to have baseline characteristics
      associated with frailty. Nevertheless, among nonosteoporotic participants,
      several characteristics increased fracture risk, including advancing age, lack of
      exercise in the last year, reduced visual contrast sensitivity, falls in the last
      year, prevalent vertebral fracture, and lower total hip BMD. These findings call
      attention to the many older women who suffer hip fracture but do not have
      particularly low antecedent BMD measures and help begin to identify risk factors
      associated with higher bone density levels.

PMID- 15728214
TI  - On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep:
      normal HPA axis activity and circadian rhythm, exemplary sleep disorders.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis plays important roles in
      maintaining alertness and modulating sleep. Dysfunction of this axis at any level
      (CRH receptor, glucocorticoid receptor, or mineralocorticoid receptor) can
      disrupt sleep. Herein, we review normal sleep, normal HPA axis physiology and
      circadian rhythm, the effects of the HPA axis on sleep, as well as the effects of
      sleep on the HPA axis. We also discuss the potential role of CRH in circadian
      dependent alerting, aside from its role in the stress response. Two clinically
      relevant sleep disorders with likely HPA axis dysfunction, insomnia and
      obstructive sleep apnea, are discussed. In insomnia, we discuss how HPA axis
      hyperactivity may be partially causal to the clinical syndrome. In obstructive
      sleep apnea, we discuss how HPA axis hyperactivity may be a consequence of the
      disorder and contribute to secondary pathology such as insulin resistance,
      hypertension, depression, and insomnia. Mechanisms by which cortisol can affect
      slow wave sleep are discussed, as is the role the HPA axis plays in secondary
      effects of primary sleep disorders.

PMID- 15728215
TI  - Onset of overweight during childhood and adolescence in relation to race and sex.
AB  - Overweight [body mass index (BMI) percentile > or = 95th] in children has become
      a major public health problem. The age when overweight begins and how it
      progresses are mostly unknown. Such information would be important for the
      optimal timing of prevention. We conducted a survival analysis on time to
      overweight and compared survival curves by race and sex. Data from a cohort of
      924 children recruited from schools in Indianapolis, IN, were analyzed. Blacks
      were at greater risk for becoming overweight than whites. Similar findings were
      obtained when at risk of overweight (BMI percentile > or = 85th and <95th) and
      overweight were considered as a single category. Twenty-five percent of blacks
      were overweight or at risk of overweight at or before age 7 yr, whereas it was
      age 11 yr in white females and age 10 yr in white males when 25% became
      overweight or were at risk of becoming overweight. The overall overweight-free
      survival curve for black females was significantly different from that for white
      females (P < 0.001), and black males were significantly different from white
      males (P = 0.04). There was no sex difference. The time to overweight during
      childhood and adolescence varies by race, indicating the need for race-specific
      timing of interventions.

PMID- 15728216
TI  - Self-limitation of intravenous tocolysis with beta2-adrenergic agonists is
      mediated through receptor G protein uncoupling.
AB  - Tocolysis with a beta-adrenergic receptor agonist is the most common approach to
      premature labor management after the 25th wk of pregnancy. However, prolonged
      treatment is associated with a marked loss of efficacy. The biochemical
      mechanisms involved remain unclear. This study was undertaken to investigate the
      effect of fenoterol on beta-adrenergic receptor signal transduction in human
      myometrium. Myometrial biopsy specimens were obtained from 40 women at cesarean
      section between the 25th and 34th wk of pregnancy. Nineteen patients had received
      no tocolysis (controls, group I) and 21 had been treated with fenoterol (<48 h in
      10, group II; > or = 48 h in 11, group III). As methods we used membrane
      preparation, adenylyl cyclase assay and cAMP RIA. Adenylyl cyclase activity was
      determined by the measurement of cAMP levels to evaluate signal transduction
      after stimulation of beta-adrenergic receptors with isoproterenol, G protein with
      GTP, and adenylyl cyclase with forskolin. The functional activity of GTP-binding
      regulatory proteins (G(s)) and adenylyl cyclase was not altered by fenoterol
      treatment. In the control group, the increase in adenylyl cyclase activity in
      response to GTP plus isoproterenol was greater than in response to GTP alone. The
      increase was reduced by 50% in group II and was insignificant in group III. There
      was no correlation between gestational age and basal adenylyl cyclase activity.
      Intravenous tocolysis with the beta2-adrenergic receptor agonist fenoterol leads
      to complete desensitization of the beta-adrenergic receptor system. In addition
      to the known reduction in receptor number (down-regulation) as underlying
      mechanism, uncoupling of the receptor from the stimulatory G protein G(s) was
      identified.

PMID- 15728217
TI  - Gender modulates sequential suppression and recovery of pulsatile growth hormone
      secretion by physiological feedback signals in young adults.
AB  - The basic mechanisms that drive the renewal of GH pulses in the human are not
      understood. Recent ensemble models predict that pulse regeneration requires
      quenching of an ongoing GH pulse by somatostatin outflow and evocation of a new
      burst by rebound GHRH release. We reasoned that related principles might explain
      why women consistently maintain higher-amplitude GH secretory bursts than men.
      Accordingly, the present study tests the hypothesis that gender modulates the
      successive dynamics of GH feedback and escape in the morning fasting, when GH
      pulses are larger in women. To this end, we infused single iv pulses of
      recombinant human (rh) GH (0, 1, and 3 microg/kg) in eight young men and six
      women on separate randomly ordered mornings fasting and quantitated serial
      inhibition and recovery of GH secretion by frequent sampling,
      immunochemiluminometry, a deconvolution procedure, and regularity analysis.
      Statistical contrasts revealed gender-comparable peak concentrations and kinetics
      of rhGH. However, women differed from men by way of: (1) 3.5- and 4.0-fold less
      feedback suppression of GH secretory-burst mass; (2) more irregular patterns of
      GH release during negative feedback; and (3) 12-and 14-fold greater postnadir
      rebound-like GH secretion after rhGH pulses. Mechanistic analyses based on a
      minimal feedback construct predicted that women generate higher endogenous
      secretagogue stimulation per unit somatostatin outflow than men. In summary,
      negative feedback induced by near-physiological GH pulses unmasks prominent
      gender-related contrasts in hypothalamo-pituitary autoregulation in young adults.
      A frugal but sufficient explanation of the ensemble outcomes is that women
      sustain greater hypothalamo-pituitary agonist input than men.

PMID- 15728218
TI  - ACCO: ASCO core curriculum outline.

PMID- 15728219
TI  - Late referrals to specialized palliative care service in Japan.
AB  - PURPOSE: To clarify the bereaved family's perceptions about the appropriateness
      of timing when physicians first referred patients to palliative care units, and
      to identify the factors contributing to family-perceived late referrals. SUBJECTS
      AND METHODS: A multicenter questionnaire survey was conducted on 630 bereaved
      family members of cancer patents who were admitted to palliative care units in
      Japan. A total of 318 responses were analyzed (effective response rate, 62%).
      RESULTS: Half of the bereaved family members regarded the timing of referrals to
      palliative care units as late or very late, while less than 5% of families
      reported early referrals (very late [19%, n = 59], late [30%, n = 96],
      appropriate [48%, n = 151], early [1.6%, n = 5], and very early [2.2%, n = 7]).
      Multiple regression analyses revealed that the independent determinants of family
      perceived late referrals were: family belief before admission that palliative
      care shortens the patient's life, insufficient in-advance discussion about
      preferred end-of-life care between patients/families and physicians, families'
      insufficient preparation for changes of patient conditions, and hospital
      admission before referrals. CONCLUSION: In Japan, the timing of referrals to
      palliative care units was late or very late from the families' perspectives. The
      independent determinants of family-perceived late referrals were: family
      misconception about palliative care, inadequate communication with physicians,
      and families' insufficient preparation for deterioration of patients' conditions.
      Systematic strategies to overcome these barriers would contribute to providing
      appropriate palliative care at all stages of cancer.

PMID- 15728220
TI  - Platinums in lung cancer: sufficient or necessary?

PMID- 15728221
TI  - High prevalence of complementary and alternative medicine use among cancer
      patients: implications for research and clinical care.

PMID- 15728222
TI  - Rhabdomyosarcoma: many similarities, a few philosophical differences.

PMID- 15728223
TI  - Late referrals to palliative care.

PMID- 15728224
TI  - Phase I study of BMS-214662, a farnesyl transferase inhibitor in patients with
      acute leukemias and high-risk myelodysplastic syndromes.
AB  - PURPOSE: To investigate the dose-limiting toxicity (DLT) and maximum-tolerated
      dose (MTD) of BMS-214662, a farnesyl transferase (FTase) inhibitor, in patients
      with acute leukemias and high-risk myelodysplastic syndromes (MDS). PATIENTS AND
      METHODS: Patients with relapsed or refractory acute leukemias or MDS, or
      previously untreated but poor candidates for chemotherapy, were included in this
      phase I study with a 3 + 3 dose escalation design. BMS-214662 was administered as
      a 1-hour bolus once weekly at doses of 42 to 157 mg/m2. Once the MTD was
      identified, the schedule was changed to a 24-hour continuous infusion once weekly
      (starting dose, 300 mg/m2). RESULTS: Thirty patients were treated at a dose of 42
      (n = 1), 56 (n = 3), 84 (n = 3), 118 (n = 13), 157 (n = 6) or 300 mg/m2 (n = 4).
      DLT occurred in 3 patients at 157 mg/m2, including nausea, vomiting, diarrhea,
      hypokalemia and cardiovascular problems. No DLT occurred with 24-hour continuous
      infusion. MTD with a 1-hour infusion was 118 mg/m2, with no MTD identified with
      the 24-hour infusion. Plasma concentrations of BMS-214662 correlated with the
      dose. Inhibition of FTase activity of approximately 60% occurred after the
      infusion with recovery to near baseline after 24 hours. Five patients had
      evidence of antileukemia activity, including two with complete remission with
      incomplete platelet recovery, one with hematologic improvement, and two with
      morphologic leukemia-free state. CONCLUSION: BMS-214662 is well tolerated at
      doses of up to 118 mg/m2 as a 1-hour infusion. The toxicity profile and efficacy
      may be improved with prolonged exposure. Further investigation of this agent in
      leukemia is warranted.

PMID- 15728225
TI  - Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence: third
      study of the International Society of Paediatric Oncology--SIOP Malignant
      Mesenchymal Tumor 89.
AB  - PURPOSE: To improve outcome for children with nonmetastatic rhabdomyosarcoma and
      to reduce systematic use of local therapy. PATIENTS AND METHODS: Five hundred
      three previously untreated patients aged from birth to 18 years, recruited
      between 1989 and 1995, were allocated to one of six treatment schedules by site
      and stage. RESULTS: Five-year overall survival (OS) and event-free survival (EFS)
      were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype
      were independent factors in predicting OS by multivariate analysis. Differences
      between EFS and OS reflected local treatment strategy and successful re-treatment
      for some patients after relapse. Patients with genitourinary nonbladder prostate
      tumors had the most favorable outcome (5-year OS, 94%): the majority were boys
      with paratesticular tumors treated successfully without alkylating agents.
      Patients with stage III disease treated with a novel six-drug combination showed
      improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84;
      5-year OS, 60% v 42%, respectively). OS was not significantly better than that
      achieved in the previous MMT 84 study, but 49% of survivors were cured without
      significant local therapy. CONCLUSION: Selective avoidance of local therapy is
      justified in some patients, though further work is required to prospectively
      identify those for whom this is most applicable. Exclusion of alkylating agents
      is justified for the most favorable subset of patients. The value of the new six
      drug chemotherapy combination is being evaluated further in a randomized study
      (MMT 95).

PMID- 15728226
TI  - Diffuse large B-cell lymphoma: clinical and biological characterization and
      outcome according to the nodal or extranodal primary origin.
AB  - PURPOSE: To study the main clinicobiologic features, response, and outcome of
      patients with diffuse large B-cell lymphoma (DLBCL) according to the primary
      site, lymph node, or different extranodal organs of the disease. PATIENTS AND
      METHODS: We included 382 patients consecutively diagnosed with DLBCL in a single
      institution during a 13-year period. Morphology, immunophenotyping, proliferation
      index, differentiation profile, bcl-2/JH rearrangement, and clinical
      characteristics were analyzed according to the primary site of the lymphoma.
      RESULTS: Sites of the disease were: lymph node, 222 cases (58%); Waldeyer's ring
      (WR), 42 (11%); and extranodal sites, 118 (31%), including GI tract in 45 cases.
      Primary extranodal cases, particularly GI, showed a bcl-6 expression more
      frequently than nodal cases. Patients with primary WR or GI lymphomas presented
      with early-stage disease, no marrow infiltration, normal serum lactate
      dehydrogenase, and low- to low/intermediate-risk international prognostic index
      (IPI) more frequently than the remainder. Complete response (CR) rate was 63%,
      with WR and GI lymphomas having a higher CR rate (85% and 80%, respectively) than
      the other groups. In the whole series, 5-year overall survival (OS) was 52%.
      Patients with WR or GI lymphomas showed better OS (5-year OS: 77% and 68%,
      respectively) than patients with nodal or other extranodal sites. In the
      multivariate analysis, IPI, bulky disease, and beta2-microglobulin were the main
      variables to predict OS; no nodal or extranodal site maintained their prognostic
      value. CONCLUSION: In the present series, the primary site of disease was
      associated with particular clinicopathologic features and outcome, though the
      latter largely depended on other factors.

PMID- 15728227
TI  - Nationwide survey on complementary and alternative medicine in cancer patients in
      Japan.
AB  - PURPOSE: To determine the prevalence of use of complementary and alternative
      medicine (CAM) by patients with cancer in Japan, and to compare the
      characteristics of CAM users and CAM nonusers. PATIENTS AND METHODS: A
      questionnaire on cancer CAM and the Hospital Anxiety and Depression Scale were
      delivered to 6,607 patients who were treated in 16 cancer centers and 40
      palliative care units. RESULTS: There were 3,461 available replies for a response
      rate of 52.4%. The prevalence of CAM use was 44.6% (1,382 of 3,100) in cancer
      patients and 25.5% (92 of 361) in noncancer patients with benign tumors. Multiple
      logistic regression analysis determined that history of chemotherapy, institute
      (palliative care units), higher education, an altered outlook on life after
      cancer diagnosis, primary cancer site, and younger age were strongly associated
      with CAM use in cancer patients. Most of the CAM users with cancer (96.2%) used
      products such as mushrooms, herbs, and shark cartilage. The motivation for most
      CAM use was recommendation from family members or friends (77.7%) rather than
      personal choice (23.3%). Positive effects were experienced by 24.3% of CAM users
      with cancer, although all of them received conventional cancer therapy
      concurrently. Adverse reactions were reported by 5.3% of cancer patients. CAM
      products were used without sufficient information by 57.3% of users with cancer
      and without a consultation with a doctor by 60.7% of users. CONCLUSION: This
      survey revealed a high prevalence of CAM use among cancer patients, without
      sufficient information or consultation with their physicians. Oncologists should
      not ignore the CAM products used by their patients because of a lack of proven
      efficacy and safety.

PMID- 15728228
TI  - Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non
      small-cell lung cancer: a phase III randomized trial.
AB  - PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG)
      and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell
      lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC
      were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1
      and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1
      and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human
      granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9
      through 15]) every 3 weeks. Results A total of 413 randomly assigned patients
      were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median
      survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the
      corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall
      response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%;
      P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2
      to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P =
      .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and
      vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in
      2% of VC-treated patients. There were five and six treatment-related deaths in
      the DG and VC arms, respectively. Quality of life was improved in DG but not in
      VC patients. CONCLUSION Although the two regimens produced comparable overall
      survival, the DG regimen had a better toxicity profile. Therefore, DG could be
      used in the first-line setting of advanced NSCLC, especially for patients who
      cannot tolerate cisplatin.

PMID- 15728229
TI  - Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell
      lung cancer: a meta-analysis of the published literature.
AB  - PURPOSE: This meta-analysis was performed to compare the activity, efficacy and
      toxicity of platinum-based versus non-platinum-based chemotherapy in patients
      with advanced non-small-cell lung cancer. METHODS: Randomized phase II and III
      clinical trials comparing first-line palliative platinum-based chemotherapy with
      the same regimen without platinum or with platinum replaced by a nonplatinum
      agent were identified by electronic searches of Medline, Embase, and Cancerlit,
      and hand searches of relevant abstract books and reference lists. Response rates,
      1-year survival, and toxicity were analyzed. Subgroups of trials using third
      generation agents were compared. RESULTS: Thirty-seven assessable trials were
      identified including 7,633 patients. A 62% increase in the odds ratio (OR) for
      response was attributable to platinum-based therapy (OR, 1.62; 95% CI, 1.46 to
      1.8; P < .0001). The 1-year survival rate was increased by 5% with platinum-based
      regimens (34% v 29%; OR, 1.21; 95% CI, 1.09 to 1.35; P = .0003). No statistically
      significant increase in 1-year survival was found when platinum therapies were
      compared to third-generation-based combination regimens (OR, 1.11; 95% CI, 0.96
      to 1.28; P = .17). The toxicity of platinum-based regimens was significantly
      higher for hematologic toxicity, nephrotoxicity, and nausea and vomiting, but not
      for neurotoxicity, febrile neutropenia rate, or toxic death rate. CONCLUSION:
      Response is significantly higher with platinum-containing regimens. One-year
      survival was not significantly prolonged when platinum-based therapies were
      compared with third-generation-based combination regimens. Toxicity is generally
      higher for platinum-based regimens.

PMID- 15728230
TI  - Twisting tails exposed: the evidence for TCR conformational change.
AB  - The mechanism by which the ligand occupancy state of the T cell receptor complex
      is converted into intracellular signaling information has been a controversial
      topic. Although the majority of structural studies argue against a conformational
      change, recent studies support the possibility for such a change within the CD3
      components of the TCR complex. In this commentary, the evidence for TCR
      conformational change is reviewed and potential mechanisms for its initiation are
      explored.

PMID- 15728231
TI  - Selecting B cells and plasma cells to memory.
AB  - Humoral immunity appears to be based on immunological memory provided by memory
      plasma cells, which secrete protective antibodies, and memory B cells, which
      react to antigen challenge by differentiating into plasma cells. How these
      differentiation pathways relate to each other, how cells are selected into these
      memory populations, and how these populations are maintained remains enigmatic.

PMID- 15728232
TI  - Movies, measurement, and modeling: the three Ms of mechanistic immunology.
AB  - Immunological phenomena that were once deduced from genetic, biochemical, and in
      situ approaches are now being witnessed in living color, in three dimensions, and
      in real time. The information in time-lapse imaging can provide valuable
      mechanistic insight into a host of processes, from cell migration to signal
      transduction. What we need now are methods to quantitate these new visual data
      and to exploit computational resources and statistical mechanical methods to
      develop mechanistic models.

PMID- 15728233
TI  - On imaging, speed, and the future of lymphocyte signaling.
AB  - During a recent roundtable discussion, we captured some personal perspectives on
      the new insight that advanced imaging techniques promise to bring to the study of
      lymphocyte signaling. The experts present their views on the power of imaging,
      the problems that need to be overcome, and the potential of the technology.

PMID- 15728234
TI  - Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic
      cells to lymphoid organs and inflamed skin.
AB  - Chemerin is a chemotactic agent that was recently identified as the ligand of
      ChemR23, a serpentine receptor expressed by activated macrophages and monocyte
      derived dendritic cells (DCs). This paper shows that blood plasmacytoid and
      myeloid DCs express functional ChemR23. Recombinant chemerin induced the
      transmigration of plasmacytoid and myeloid DCs across an endothelial cell
      monolayer. In secondary lymphoid organs (lymph nodes and tonsils), ChemR23 is
      expressed by CD123(+) plasmacytoid DCs and by CD1a(+) DC-SIGN(+) DCs in the
      interfollicular T cell area. ChemR23(+) DCs were also observed in dermis from
      normal skin, whereas Langerhans cells were negative. Chemerin expression was
      selectively detected on the luminal side of high endothelial venules in secondary
      lymphoid organs and in dermal endothelial vessels of lupus erythematosus skin
      lesions. Chemerin(+) endothelial cells were surrounded by ChemR23(+) plasmacytoid
      DCs. Thus, ChemR23 is expressed and functional in plasmacytoid DCs, a property
      shared only by CXCR4 among chemotactic receptors. This finding, together with the
      selective expression of the cognate ligand on the luminal side of high
      endothelial venules and inflamed endothelium, suggests a key role of the
      ChemR23/chemerin axis in directing plasmacytoid DC trafficking.

PMID- 15728235
TI  - T cell receptor engagement by peptide-MHC ligands induces a conformational change
      in the CD3 complex of thymocytes.
AB  - The T cell receptor (TCR) can recognize a variety of cognate peptide/major
      histocompatibility complex (pMHC) ligands and translate their affinity into
      distinct cellular responses. To achieve this, the nonsignaling alphabeta
      heterodimer communicates ligand recognition to the CD3 signaling subunits by an
      unknown mechanism. In thymocytes, we found that both positive- and negative
      selecting pMHC ligands expose a cryptic epitope in the CD3 complex upon TCR
      engagement. This conformational change is induced in vivo and requires the
      expression of cognate MHC. We conclude that TCR engagement with a cognate pMHC
      ligand induces a conformational change in the CD3 complex of thymocytes and
      propose that this marks an initial event during thymic selection that signals the
      recognition of self-antigen.

PMID- 15728236
TI  - An orderly inactivation of intracellular retention signals controls surface
      expression of the T cell antigen receptor.
AB  - Exit from the endoplasmic reticulum (ER) is an important checkpoint for proper
      assembly of multimeric plasma membrane receptors. The six subunits of the T cell
      receptor (TCR; TCRalpha, TCRbeta, CD3gamma, CD3delta, CD3epsilon, and CD3zeta)
      are each endowed with ER retention/retrieval signals, and regulation of its
      targeting to the plasma membrane is therefore especially intriguing. We have
      studied the importance of the distinct ER retention signals at different stages
      of TCR intracellular assembly. To this end, we have characterized first the
      presence of ER retention signals in CD3gamma. Despite the presence of multiple ER
      retention signals in CD3gamma, epsilongamma dimers reach the cell surface when
      the single CD3epsilon ER retention signal is deleted. Furthermore, inclusion of
      this CD3epsilon mutant promoted plasma membrane expression of incomplete
      alphabetagammaepsilon and alphabetadeltaepsilon complexes without CD3zeta. It
      therefore appears that the CD3epsilon ER retention signal is dominant and that it
      is only overridden upon the incorporation of CD3zeta. We propose that the
      stepwise assembly of the TCR complex guarantees that all assembly intermediates
      have at least one functional ER retention signal and that only a full signaling
      competent TCR complex is expressed on the cell surface.

PMID- 15728237
TI  - Enhanced autoantigen expression in regenerating muscle cells in idiopathic
      inflammatory myopathy.
AB  - Unique autoantibody specificities are strongly associated with distinct clinical
      phenotypes, making autoantibodies useful for diagnosis and prognosis. To
      investigate the mechanisms underlying this striking association, we examined
      autoantigen expression in normal muscle and in muscle from patients with
      autoimmune myositis. Although myositis autoantigens are expressed at very low
      levels in control muscle, they are found at high levels in myositis muscle.
      Furthermore, increased autoantigen expression correlates with differentiation
      state, such that myositis autoantigen expression is increased in cells that have
      features of regenerating muscle cells. Consistent with this, we found that
      cultured myoblasts express high levels of autoantigens, which are strikingly down
      regulated as cells differentiate into myotubes in vitro. These data strongly
      implicate regenerating muscle cells rather than mature myotubes as the source of
      ongoing antigen supply in autoimmune myositis. Myositis autoantigen expression is
      also markedly increased in several cancers known to be associated with autoimmune
      myositis, but not in their related normal tissues, demonstrating that tumor cells
      and undifferentiated myoblasts are antigenically similar. We propose that in
      cancer-associated myositis, an autoimmune response directed against cancer cross
      reacts with regenerating muscle cells, enabling a feed-forward loop of tissue
      damage and antigen selection. Regulating pathways of antigen expression may
      provide unrecognized therapeutic opportunities in autoimmune diseases.

PMID- 15728238
TI  - The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival.
AB  - The pre-T cell receptor (TCR) is expressed early during T cell development and
      imposes a tight selection for differentiating T cell progenitors. Pre-TCR
      expressing cells are selected to survive and differentiate further, whereas pre
      TCR(-) cells are "negatively" selected to die. The mechanisms of pre-TCR-mediated
      survival are poorly understood. Here, we describe the induction of the
      antiapoptotic gene BCL2A1 (A1) as a potential mechanism regulating inhibition of
      pre-T cell death. We characterize in detail the signaling pathway involved in A1
      induction and show that A1 expression can induce pre-T cell survival by
      inhibiting activation of caspase-3. Moreover, we show that in vitro "knockdown"
      of A1 expression can compromise survival even in the presence of a functional pre
      TCR. Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to
      T cell leukemia in both mice and humans.

PMID- 15728239
TI  - Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory
      responses.
AB  - To mount an effective type 1 immune response, type 1 T helper (Th1) cells must
      produce inflammatory cytokines and simultaneously suppress the expression of
      antiinflammatory cytokines. How these two processes are coordinately regulated at
      the molecular level is still unclear. In this paper, we show that the proto
      oncogene E26 transformation-specific-1 (Ets-1) is necessary for T-bet to promote
      interferon-gamma production and that Ets-1 is essential for mounting effective
      Th1 inflammatory responses in vivo. In addition, Ets-1-deficient Th1 cells also
      produce a very high level of interleukin 10. Thus, Ets-1 plays a crucial and
      unique role in the reciprocal regulation of inflammatory and antiinflammatory Th
      responses.

PMID- 15728240
TI  - Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production
      and augment T helper type 2 cell polarization.
AB  - Pollen grains induce allergies in susceptible individuals by release of allergens
      upon contact with mucosal membranes of the upper respiratory tract. We recently
      demonstrated that pollen not only function as allergen carriers but also as rich
      sources of bioactive lipids that attract cells involved in allergic inflammation
      such as neutrophils and eosinophils. Here we demonstrate that soluble factors
      from birch (Betula alba L.) pollen activate human dendritic cells (DCs) as
      documented by phenotypical and functional maturation and altered cytokine
      production. Betula alba L. aqueous pollen extracts (Bet.-APE) selectively
      inhibited interleukin (IL)-12 p70 production of lipopolysaccharide (LPS)- or
      CD40L-activated DC, whereas IL-6, IL-10, and TNFalpha remained unchanged.
      Presence of Bet.-APE during DC activation resulted in DC with increased T helper
      type 2 (Th2) cell and reduced Th1 cell polarizing capacity. Chemical analysis of
      Bet.-APE revealed the presence of phytoprostanes (dinor isoprostanes) with
      prostaglandin E(1)-, F(1)-, A(1)-, or B(1)-ring systems of which only E(1)
      phytoprostanes dose dependently inhibited the LPS-induced IL-12 p70 release and
      augmented the Th2 cell polarizing capacity of DC. These results suggest that
      pollen-derived E(1)-phytoprostanes not only resemble endogenous prostaglandin
      E(2) structurally but also functionally in that they act as regulators that
      modulate human DC function in a fashion that favors Th2 cell polarization.

PMID- 15728241
TI  - Clearance of apoptotic neurons without inflammation by microglial triggering
      receptor expressed on myeloid cells-2.
AB  - Elimination of apoptotic neurons without inflammation is crucial for brain tissue
      homeostasis, but the molecular mechanism has not been firmly established.
      Triggering receptor expressed on myeloid cells-2 (TREM2) is a recently identified
      innate immune receptor. Here, we show expression of TREM2 in microglia. TREM2
      stimulation induced DAP12 phosphorylation, extracellular signal-regulated kinase
      phosphorylation, and cytoskeleton reorganization and increased phagocytosis.
      Knockdown of TREM2 in microglia inhibited phagocytosis of apoptotic neurons and
      increased gene transcription of tumor necrosis factor alpha and nitric oxide
      synthase-2, whereas overexpression of TREM2 increased phagocytosis and decreased
      microglial proinflammatory responses. Thus, TREM2 deficiency results in impaired
      clearance of apoptotic neurons and inflammation that might be responsible for the
      brain degeneration observed in patients with polycystic lipomembranous
      osteodysplasia with sclerosing leukoencephalopathy/Nasu-Hakola disease.

PMID- 15728242
TI  - Differential capability for phagocytosis of apoptotic and necrotic leukemia cells
      by human peripheral blood dendritic cell subsets.
AB  - CD11c+ dendritic cells (DC) and plasmacytoid DC (PDC) are the two major DC
      subsets in human peripheral blood. For the purpose of immunotherapy with DC, it
      is important to investigate the phagocytosis of killed tumor cells by different
      DC subsets. Using immature monocyte-derived DC (iMoDC) as reference, we have
      compared the ability of CD11c+ DC and PDC to phagocytose apoptotic and necrotic
      K562 leukemia cells. Freshly isolated CD11c+ DC phagocytosed apoptotic and
      necrotic K562 cells, whereas PDC did not show any evidence of uptake of dead
      cells. Blocking studies showed that CD36 is importantly involved in uptake of
      apoptotic and necrotic material. CD91 and CD11c were also involved. In addition,
      we found that beta5 integrin was expressed on CD11c+ DC but not in its classical
      association with alphaV. Uptake of apoptotic K562 cells by CD11c+ DC was
      increased following incubation with granulocyte macrophage-colony stimulating
      factor (GM-CSF) and interleukin (IL)-4, alone or in combination with transforming
      growth factor-beta1, to levels comparable with those observed for iMoDC.
      Phagocytosis of dead cellular material by the GM-CSF/IL-4-treated CD11c+ DC was
      largely restricted to a subset expressing low levels of human leukocyte antigen
      DR and CD83. Thus, the relationship between phagocytosis of antigenic material
      and expression of maturation-related cell-surface molecules is similar for CD11c+
      DC and MoDC. We conclude that CD11c+ DC in peripheral blood are precursor cells,
      which under the influence of cytokines, differentiate to cells with DC phenotype
      and function.

PMID- 15728243
TI  - Inflammation-mediated dysfunction and apoptosis in pancreatic islet
      transplantation: implications for intrahepatic grafts.
AB  - Recent advances in clinical protocols have improved the outcomes of pancreatic
      islet transplantation (PIT), yet PIT recipients typically require pancreatic
      islet grafts derived from multiple donors to achieve insulin independence. This
      along with experimental models of syngeneic PIT, showing that up to 60% of
      pancreatic islet tissue undergoes apoptosis within the first several days post
      transplantation, strongly suggest the involvement of nonalloantigen-specific,
      inflammatory events in partial destruction of the graft following PIT.
      Interleukin-1beta appears to be among the most important inflammatory mediators,
      causing pancreatic islet dysfunction and apoptosis through the up-regulation of
      inducible nitric oxide (NO) synthase and cyclooxygenase-2. Kupffer cells secrete
      many molecules, including cytokines, NO, and free radicals, which are known to be
      directly toxic to the pancreatic islets, and depletion or inhibition of Kupffer
      cells improves outcomes following experimental PIT. Immediately after
      transplantation, the pancreatic islets are perfused only by portal vein blood
      until the process of angiogenesis restores arterial blood flow some 7-10 days
      later. This delayed vascularization may have implications for the expression of
      leukocyte adhesion molecules, the effects of free radicals, and the role of
      ischemia-reperfusion injury. Finally, in the immediate post-transplant period,
      hepatocytes may contribute to pancreatic islet injury through the production of
      NO. This paper reviews literature regarding the inflammatory events that follow
      PIT as well as the pathogenesis of diabetes and the pathophysiology of hepatic
      ischemia-reperfusion and their relation to the survival and function of
      intrahepatic pancreatic islet grafts.

PMID- 15728244
TI  - The expression and roles of Toll-like receptors in the biology of the human
      neutrophil.
AB  - Neutrophils are amongst the first immune cells to arrive at sites of infection,
      where they initiate antimicrobial and proinflammatory functions, which serve to
      contain infection. Sensing and defeating microbial infections are daunting tasks
      as a result of their molecular heterogeneity; however, Toll-like receptors (TLRs)
      have emerged as key components of the innate-immune system, activating multiple
      steps in the inflammatory reaction, eliminating invading pathogens, and
      coordinating systemic defenses. Activated neutrophils limit infection via the
      phagocytosis of pathogens and by releasing antimicrobial peptides and
      proinflammatory cytokines and generating reactive oxygen intermediates. Through
      the production of chemokines, they additionally recruit and activate other immune
      cells to aid the clearance of the microbes and infected cells and ultimately,
      mount an adaptive immune response. In acute inflammation, influx of neutrophils
      from the circulation leads to extremely high cell numbers within tissues, which
      is exacerbated by their delayed, constitutive apoptosis caused by local
      inflammatory mediators, potentially including TLR agonists. Neutrophil apoptosis
      and safe removal by phagocytic cells limit tissue damage caused by release of
      neutrophil cytotoxic granule contents. This review addresses what is currently
      known about the function of TLRs in the biology of the human neutrophil,
      including the regulation of TLR expression, their roles in cellular recruitment
      and activation, and their ability to delay apoptotic cell death.

PMID- 15728245
TI  - Regulated recruitment of DC-SIGN to cell-cell contact regions during zymosan
      induced human dendritic cell aggregation.
AB  - Zymosan is a beta-glucan, mannan-rich yeast particle widely used to activate the
      inflammatory response of immune cells. We studied the zymosan-binding potential
      of human dendritic cells (hDCs) by using specific carbohydrate inhibitors and
      blocking monoclonal antibodies. We show that DC-specific intercellular adhesion
      molecule-grabbing nonintegrin (DC-SIGN) is a major nonopsonic recognition
      receptor for zymosan on hDCs. Indeed, blocking of DC-SIGN inhibited the
      inflammatory response of DCs to zymosan. We compared the zymosan-binding capacity
      of hDC-SIGN to that of Dectin-1 and complement receptor 3 (CR3), which are
      receptors involved in the nonopsonic recognition of these yeast-derived
      particles. Dectin-1- and DC-SIGN-K562 cells bound to zymosan particles, whereas
      CR3-K562 cells did not. DC-SIGN and Dectin-1 were also expressed in COS cells to
      compare their ability to trigger particle internalization in a nonphagocytic cell
      line. DC-SIGN transfectants were unable to internalize bound particles,
      indicating that DC-SIGN is primarily involved in recognition but not in particle
      internalization. Zymosan induced a rapid DC aggregation that was accompanied by a
      dramatic change of DC-SIGN distribution in the plasma membrane. Under resting
      conditions, DC-SIGN was diffusely distributed through the cell surface,
      displaying clusters at the free leading edge. Upon zymosan treatment, DC-SIGN was
      markedly redistributed to cell-cell contacts, supporting an adhesion role in DC
      DC interactions. The mechanism(s) supporting DC-SIGN-mediated intercellular
      adhesion were further investigated by using DC-SIGN-K562 aggregation. DC-SIGN was
      highly concentrated at points of cell-cell contact, suggesting a role for
      enhanced avidity during DC-SIGN-mediated intercellular adhesion.

PMID- 15728246
TI  - Up-regulation of the interferon-inducible IFI16 gene by oxidative stress triggers
      p53 transcriptional activity in endothelial cells.
AB  - Reactive oxygen species (ROS), including hydrogen peroxide (H2O2), induces injury
      of endothelium in a variety of pathophysiological conditions, such as
      inflammation, aging, and cancer. In our study, we characterized the signaling
      pathway linking oxidative stress induced by sublethal concentrations of H2O2 to
      p53 in primary human endothelial cells through the interferon (IFN)-inducible
      gene IFI16. Induction of IFI16 by H2O2 was concentration- and time-dependent
      (maximum at 50 microM, 6 h after treatment) and down-regulated by pretreatment
      with N-acetyl-L-cysteine, which acts as an antioxidant. This pathway is a general
      response to ROS and not specific to H2O2 treatment, as two other ROS-generating
      compounds, i.e., S-nitroso-N-acetylpenicillamine and tert-butyl hydroperoxide,
      were equally capable to induce IFI16. Moreover, IFI16 up-regulation is a result
      of protein accumulation, as expression of corresponding mRNA, assessed by real
      time polymerase chain reaction, was not affected. To investigate the mechanism of
      IFI16 accumulation, cells were incubated for 6 h in the presence of H2O2 or IFN
      beta, and then cycloheximide was added to inhibit further protein synthesis. The
      half-life of IFI16 protein was found to be significantly increased in H2O2
      treated cells compared with IFN-beta-treated cells (t1/2 = 120 min vs. > 30 min
      in H2O2- vs. IFN-beta-treated cells, respectively). An increase of IFI16 was
      accompanied by interaction with p53 phosphorylated at its N terminus, as shown by
      immunoprecipitation experiments. Moreover, binding to IFI16 resulted in its
      transcriptional activation as shown by an increase in the activity of a reporter
      gene driven by p53-responsive sequences derived from the p21(WAF1) promoter,
      along with an increase in the p21 mRNA and protein levels. Altogether, these
      results demonstrate a novel role of IFI16 in the signal transduction pathway that
      leads to p53 activation by oxidative stress in endothelial cells.

PMID- 15728247
TI  - Herpesvirus saimiri-transformed CD8+ T cells as a tool to study Chediak-Higashi
      syndrome cytolytic lymphocytes.
AB  - Cytolytic CD8+ T lymphocytes are the main cell type involved in the fatal
      lymphoproliferative-accelerated phase of the Chediak-Higashi syndrome (CHS). To
      generate a cellular tool to study the defects of this T cell subset in vitro, we
      have used Herpesvirus saimiri, a lymphotropic virus that transforms human T
      lymphocytes into extended growth and in addition, endows them with natural killer
      (NK) features. Transformed CHS CD8+ T cells were generated and characterized in
      comparison with healthy controls. The results showed that transformed CHS T cells
      maintained the defects described in primary CHS lymphocytes, such as giant
      secretory lysosomes and impaired NK and T cell receptor/CD3-induced, perforin
      mediated cytolytic activity [which, however, could be restored after extended
      culture in the presence of interleukin-2 (IL-2)]. Upon activation with phorbol
      ester plus calcium ionophore or upon extended culture with IL-2, transformed CHS
      T cells showed normal, perforin-independent plasma membrane CD178/CD95L/FasL
      mediated cytolytic activity but negligible secretion of microvesicle-bound CD95L.
      Transformed (and primary) CHS T cells were otherwise normal for cytolysis
      independent activation functions, such as proliferation, surface expression of
      several activation markers including major histocompatibility complex class II,
      and cytokine or surface activation-marker induction. Therefore, the CHS protein
      [CHS1/LYST (for lysosomal traffic regulator)] can be dispensable for certain NK
      and T cell cytolytic activities of activated CHS CD8+ T lymphocytes, but it seems
      to be required for microvesicle secretion of CD95L. We conclude that transformed
      CHS T cells may be useful as a tool to study in vitro the relative role of
      CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation.

PMID- 15728248
TI  - Accumulation of an intron-retained mRNA for granulocyte macrophage-colony
      stimulating factor receptor common beta chain in neutrophils of myelodysplastic
      syndromes.
AB  - We recently identified a reduction in the neutrophil surface expression of common
      beta chain (beta c) of the receptor for granulocyte macrophage-colony stimulating
      factor (GM-CSF) in the patients with myelodysplastic syndromes (MDS). To
      determine the etiology of the impaired beta c expression, beta c mRNA from
      neutrophilic granulocytes of MDS patients and healthy controls was analyzed by a
      combination of direct reverse transcriptase-polymerase chain reaction-based
      single-strand conformational polymorphism and sequencing. Nine different beta c
      transcripts were detected, but none was specific for MDS. However, one of the
      transcripts (beta c79) containing a 79-base intron insertion between exons V and
      VI was significantly increased in MDS. This 27-kd isoform consisted of the beta c
      N-terminal 182 amino acids followed by a new 84-amino-acid sequence. beta c79 was
      overexpressed in all MDS subtypes. No genomic mutations were detected within the
      intron or at the intron/exon boundaries. The isoform is predominantly located in
      the cytoplasm by Western blot analysis and was unable to generate high-affinity
      binding sites or transduce a signal for proliferation when coexpressed with the
      receptor for human GM-CSF alpha chain. Our study suggests that the accumulation
      of the abnormal beta c transcripts with intron V retention results in the
      reduction in cell-surface expression of beta c observed in MDS.

PMID- 15728249
TI  - Mammalian Bet3 functions as a cytosolic factor participating in transport from
      the ER to the Golgi apparatus.
AB  - The TRAPP complex identified in yeast regulates vesicular transport in the early
      secretory pathway. Although some components of the TRAPP complex are structurally
      conserved in mammalian cells, the function of the mammalian components has not
      been examined. We describe our biochemical and functional analysis of mammalian
      Bet3, the most conserved component of the TRAPP complex. Bet3 mRNA is
      ubiquitously expressed in all tissues. Antibodies raised against recombinant Bet3
      specifically recognize a protein of 22 kDa. In contrast to yeast Bet3p, the
      majority of Bet3 is present in the cytosol. To investigate the possible
      involvement of Bet3 in transport events in mammalian cells, we utilized a semi
      intact cell system that reconstitutes the transport of the envelope glycoprotein
      of vesicular stomatitis virus (VSV-G) from the ER to the Golgi apparatus. In this
      system, antibodies against Bet3 inhibit transport in a dose-dependent manner, and
      cytosol that is immunodepleted of Bet3 is also defective in this transport. This
      defect can be rescued by supplementing the Bet3-depleted cytosol with recombinant
      GST-Bet3. We also show that Bet3 acts after COPII but before Rab1, alpha-SNAP and
      the EGTA-sensitive stage during ER-Golgi transport. Gel filtration analysis
      demonstrates that Bet3 exists in two distinct pools in the cytosol, the high
      molecular-weight pool may represent the TRAPP complex, whereas the other probably
      represents the monomeric Bet3.

PMID- 15728250
TI  - Stress alters the subcellular distribution of hSlu7 and thus modulates
      alternative splicing.
AB  - During pre-mRNA splicing, introns are removed and exons are ligated to form an
      mRNA. Exon choice is determined by different nuclear protein concentrations
      varying among tissues and cell types or by developmental stage. These can be
      altered by different cellular circumstances such as physiological stimuli,
      environmental effects and phosphorylation state. The splicing factor hSlu7 plays
      an important role in 3' splice site selection during the second step of splicing
      in vitro and has been suggested to affect alternative splicing in vivo. Our
      results indicate that an ultraviolet-C (UV-C) stress stimulus triggers changes in
      the alternative splicing patterns of cellular genes by decreasing the nuclear
      concentration of hSlu7 through the modulation of its nucleus-to-cytoplasm
      transport. This shift is mostly dependent on the Jun N-terminal kinase (JNK)
      cascade. Although we found by RNAi knockdown that hSlu7 is not essential for cell
      viability, its nuclear concentration effects exon choice and inclusion:skipping
      ratio of alternative splicing. A possible spatial and temporal regulatory
      mechanism by which hSlu7 protein levels are regulated within the nucleus is
      suggested, thus implying a broad effect of hSlu7 on alternative splicing.

PMID- 15728251
TI  - Identification of a novel tubulin-destabilizing protein related to the chaperone
      cofactor E.
AB  - Factors that regulate the microtubule cytoskeleton are critical in determining
      cell behavior. Here we describe the function of a novel protein that we term E
      like based on its sequence similarity to the tubulin-specific chaperone cofactor
      E. We find that upon overexpression, E-like depolymerizes microtubules by
      committing tubulin to proteosomal degradation. Our data suggest that this
      function is direct and is based on the ability of E-like to disrupt the tubulin
      heterodimer in vitro. Suppression of E-like expression results in an increase in
      the number of stable microtubules and a tight clustering of endocellular
      membranes around the microtubule-organizing center, while the properties of
      dynamic microtubules are unaffected. These observations define E-like as a novel
      regulator of tubulin stability, and provide a link between tubulin turnover and
      vesicle transport.

PMID- 15728252
TI  - Alpha3beta1 integrin regulates MMP-9 mRNA stability in immortalized
      keratinocytes: a novel mechanism of integrin-mediated MMP gene expression.
AB  - Matrix metalloproteinases facilitate cell migration and tumor invasion through
      their ability to proteolyse the extracellular matrix. The laminin-binding
      integrin alpha3beta1 is expressed at high levels in squamous cell carcinomas and
      in normal keratinocytes during cutaneous wound healing. We showed previously that
      alpha3beta1 is required for MMP-9/gelatinase B secretion in immortalized mouse
      keratinocytes (MK cells) and that this regulation was acquired as part of the
      immortalized phenotype, suggesting a possible role for alpha3beta1 during
      malignant conversion. In the current study, we identify a novel mechanism whereby
      alpha3beta1 regulates the induction of MMP-9 expression that occurs in response
      to activation of a MAPK kinase (MEK)/extracellular signal-regulated kinase (ERK)
      pathway. Inhibition of MEK/ERK signaling in wild-type MK cells with a
      pharmacological inhibitor, U0126, showed that ERK activation was necessary for
      high levels of endogenous MMP-9 gene expression and activity of a transfected MMP
      9 promoter. Furthermore, activation of MEK/ERK signaling in these cells with an
      oncogenic mutant of Ras, RasV12, increased both endogenous MMP-9 gene expression
      and MMP-9 promoter activity. Experiments with alpha3beta1-deficient MK cells
      revealed that alpha3beta1 was required for both baseline levels and RasV12
      induced levels of MMP-9 mRNA expression. However, alpha3beta1 was not required
      for RasV12-mediated activation of ERK or for ERK-dependent MMP-9 promoter
      activity. Direct comparison of mRNA turnover in the wild type and alpha3-null MK
      cells identified a requirement for alpha3beta1 in stabilization of MMP-9 mRNA
      transcripts. These results identify a novel function for integrins in promoting
      mRNA stability as a mechanism to potentiate MAPK-mediated gene expression. They
      also suggest a role for alpha3beta1 in maintaining high levels of MMP-9 mRNA
      expression in response to oncogenic activation of MEK/ERK signaling pathways.

PMID- 15728253
TI  - Cdc42 downregulates MMP-1 expression by inhibiting the ERK1/2 pathway.
AB  - The small GTPases of the Rho family are key intermediates in cellular signalling
      triggered by activated cell-adhesion receptors. In this study, we took advantage
      of RNA interference (RNAi) using small interfering RNAs (siRNAs) to define the
      roles of the best-characterized members of the RhoGTPase family, RhoA, Rac1 and
      Cdc42, in the control of MMP-1, MMP-2 and type-I-collagen expression in normal
      human skin fibroblasts (HSFs). A specific and long-lasting repression, up to 7
      days after transfection, of the three GTPases was achieved by transient
      transfection of specific siRNA. The silencing of Cdc42, but not that of RhoA or
      Rac1, induced a 15-fold increase in MMP-1 secretion. This upregulation was
      confirmed at the mRNA level and observed with two different siRNAs targeting
      Cdc42. Such a regulation was also observed in various human cell lines and was
      rescued by re-expressing wild-type Cdc42 encoded by a construct bearing silent
      mutations impeding its recognition by the siRNA. By contrast, MMP-2 and type-I
      collagen expression was not affected by the individual silencing of each Rho
      GTPase. Cytokine protein array, enzyme-linked immunosorbent assays and reverse
      transcription PCR measurements revealed that ablation of Cdc42 induced an
      overexpression of interleukin 8 and MCP-1. Although these cytokines are known to
      induce the expression of MMP-1, we showed that they were not involved in the
      Cdc42-mediated upregulation of MMP-1. Silencing of Cdc42 also induced an
      increased phosphorylation of ERK1/2 and p38 MAP kinase. The use of chemical
      inhibitors on Cdc42-ablated cells revealed that the upregulation of MMP-1 is
      dependent on the ERK1/2 pathways, whereas the p38 MAP kinase pathway displayed an
      inhibitory role. Simultaneous knock-down of two or three Rho GTPases allowed us
      to demonstrate that the RhoA-ROCK pathway was not involved in this regulation but
      that the silencing of Rac1 reduced the effect of Cdc42 suppression. These data
      suggest that, in vivo, when cell/extracellular-matrix interactions via integrins
      induce cytoskeleton organization, MMP-1 expression is maintained at a low level
      by Cdc42 via a repression of the Rac1 and ERK1/2 pathways. Therefore, Cdc42
      contributes to ECM homeostasis and connective tissue integrity.

PMID- 15728254
TI  - PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1
      promoter.
AB  - PITX2, beta-catenin and lymphoid enhancer factor (LEF-1) are required for the
      inductive formation of several epithelial-derived organs, including teeth. Lef-1
      is expressed in the dental epithelium after Pitx2, and both factors have
      overlapping expression patterns in the tooth bud and cap stages. Our analysis of
      Pitx2-/- mutant mice showed reduced Lef-1 expression in facial tissues by RT-PCR
      and quantitative RT-PCR. Consistent with these results we show that the human 2.5
      kb LEF-1 promoter is activated by PITX2. Furthermore, the LEF-1 promoter is
      differentially activated by PITX2 isoforms, which are co-expressed in dental
      epithelium. The 2.5 kb LEF-1 promoter contains two regions that act to inhibit
      its transcription in concert with PITX2. The proximal region contains a Wnt
      responsive element (WRE) that attenuates PITX2 activation. LEF-1 cannot
      autoregulate LEF-1 expression; however co-transfection of PITX2 and LEF-1 result
      in a synergistic activation of the 2.5 kb LEF-1 promoter. LEF-1 specifically
      interacts with the PITX2 C-terminal tail. Deletion of a distal 800 bp segment of
      the LEF-1 promoter resulted in enhanced PITX2 activation, and increased
      synergistic activation in the presence of LEF-1. Furthermore, beta-catenin in
      combination with PITX2 synergistically activates the LEF-1 promoter and this
      activation is independent of the Wnt-responsive element. beta-catenin directly
      interacts with PITX2 to synergistically regulate LEF-1 expression. We show a new
      mechanism where LEF-1 expression is regulated through PITX2, LEF-1 and beta
      catenin direct physical interactions. LEF-1 and beta-catenin interactions with
      PITX2 provide new mechanisms for the regulation of PITX2 transcriptional
      activity.

PMID- 15728255
TI  - Sphingosine 1-phosphate induces cytoskeletal reorganization in C2C12 myoblasts:
      physiological relevance for stress fibres in the modulation of ion current
      through stretch-activated channels.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive lipid that is abundantly present in
      the serum and mediates multiple biological responses. With the aim of extending
      our knowledge on the role played by S1P in the regulation of cytoskeletal
      reorganization, native as well as C2C12 myoblasts stably transfected with green
      fluorescent protein (GFP)-tagged alpha- and beta-actin constructs were stimulated
      with S1P (1 microM) and observed under confocal and multiphoton microscopes. The
      addition of S1P induced the appearance of actin stress fibres and focal adhesions
      through Rho- and phospholipase D (PLD)-mediated pathways. The cytoskeletal
      response was dependent on the extracellular action of S1P through its specific
      surface receptors, since the intracellular delivery of the sphingolipid by
      microinjection was unable to modify the actin cytoskeletal assembly.
      Interestingly, it was revealed by whole-cell patch-clamp that S1P-induced stress
      fibre formation was associated with increased ion currents and conductance
      through stretch-activated channels (SACs), thereby suggesting a possible
      regulatory role for organized actin in channel sensitivity. Experiments aimed at
      stretching the plasma membrane of C2C12 cells, using the cantilever of an atomic
      force microscope, indicated that there was a Ca2+ influx through putative SACs.
      In conclusion, the present data suggest novel mechanisms of S1P signalling
      involving actin cytoskeletal reorganization and Ca2+ elevation through SACs that
      might influence myoblastic functions.

PMID- 15728256
TI  - Cbl-mediated ubiquitination of alpha5 integrin subunit mediates fibronectin
      dependent osteoblast detachment and apoptosis induced by FGFR2 activation.
AB  - Fibroblast growth factor receptor signaling is an important mechanism regulating
      osteoblast function. To gain an insight into the regulatory role of FGF receptor
      2 (FGFR2) signaling in osteoblasts, we investigated integrin-mediated attachment
      and cell survival in human calvarial osteoblasts expressing activated FGFR2.
      FGFR2 activation reduced osteoblast attachment on fibronectin. This was
      associated with reduced expression of the alpha5 integrin subunit normally
      expressed in human calvarial osteoblasts in vivo. Treatment with lactacystin, a
      potent inhibitor of proteasome, restored alpha5 integrin levels in FGFR2 mutant
      osteoblasts. Immunoprecipitation analysis showed that alpha5 integrin interacts
      with both the E3 ubiquitin ligase Cbl and ubiquitin. Immunocytochemistry revealed
      that alpha5 integrin colocalizes with FGFR2 and Cbl at the leading edge in
      membrane ruffle regions. Transfection with the 70Z-Cbl mutant lacking the RING
      domain required for Cbl-ubiquitin interaction, or with the G306E Cbl mutant that
      abolishes the binding ability of Cbl phosphotyrosine-binding domain restored
      alpha5 integrin levels. This suggests that Cbl-mediated ubiquitination plays an
      essential role in alpha5 integrin proteasome degradation induced by FGFR2
      activation. Reduced alpha5 integrin expression was associated with an increased
      Bax/Bcl-2 ratio and increased caspase-9 and -3 activities in FGFR2 mutant
      osteoblasts. Forced expression of alpha5 integrin rescued cell attachment and
      corrected both the Bax/Bcl-2 ratio and caspase-3 and caspase-9 activities in
      FGFR2 mutant osteoblasts. We show that Cbl recruitment induced by FGFR2
      activation triggers alpha5 integrin degradation by the proteasome, which results
      in reduced osteoblast attachment on fibronectin and caspase-dependent apoptosis.
      This identifies a functional role of the alpha5 integrin subunit in the induction
      of apoptosis triggered by FGFR2 activation in osteoblasts, and reveals that a Cbl
      dependent mechanism is involved in the coordinated regulation of cell apoptosis
      induced by alpha5 integrin degradation.

PMID- 15728257
TI  - Golgi polarization in a strong electric field.
AB  - Directional cell migration requires proper cell polarization. The redistribution
      of the Golgi apparatus is an important event in the polarization and migration of
      many types of cells, as a polarized Golgi supplies membrane components for
      leading edge protrusion. Direct current electric fields induce directional cell
      migration in a wide variety of cells. Here we show that electric fields of 300
      mV/mm induce robust Golgi polarization and directional cell migration in CHO
      cells. Asymmetric Src and PI 3-kinase signalling as well as actin polymerization
      are essential for electric field-induced Golgi polarization and directional cell
      migration. The Golgi polarizes at the same time as cells change morphology and
      migrate directionally in response to an electric field. Golgi polarization in
      turn significantly reinforces and maintains optimal electrotaxis. It is not known
      whether electrical signals, when contradicting other directional cues, are still
      able to polarize cells and direct cell migration. Most strikingly, Golgi
      polarization and cell migration simply follow the direction of an applied
      electric field and ignore all other cues generated by wounding a monolayer of CHO
      cells. Thus, an electric field of 300 mV/mm is the predominant cue to polarize
      the Golgi and direct cell migration mediated by PI 3-kinase and Src signalling.

PMID- 15728258
TI  - Sec6 mutations and the Drosophila exocyst complex.
AB  - To allow a detailed analysis of exocyst function in multicellular organisms, we
      have generated sec6 mutants in Drosophila. We have used these mutations to
      compare the phenotypes of sec6 and sec5 in the ovary and nervous system, and we
      find them to be similar. We also find that Sec5 is mislocalized in sec6 mutants.
      Additionally, we have generated an epitope-tagged Sec8 that localized with Sec5
      on oocyte membranes and was mislocalized in sec5 and sec6 germ-line clones. This
      construct further revealed a genetic interaction of sec8 and sec5. These data,
      taken together, provide new information about the organization of the exocyst
      complex and suggest that Sec5, Sec6 and Sec8 act as a complex, each member
      dependent on the others for proper localization and function.

PMID- 15728259
TI  - Assaults on transport workers.

PMID- 15728260
TI  - The post-translational modifications of the nuclear encoded subunits of complex I
      from bovine heart mitochondria.
AB  - Bovine complex I is an assembly of 46 different proteins. Seven of them are
      encoded in mitochondrial DNA, and the rest are nuclear gene products that are
      imported into the organelle. Fourteen of the nuclear encoded subunits have
      modified N termini. Many of these post-translational modifications have been
      deduced previously from intact protein masses. These assignments have been
      verified by mass spectrometric analysis of peptides. Thirteen of them are N-alpha
      acetylated, and a 14th, subunit B18, is N-alpha-myristoylated. Subunit B18 forms
      part of the membrane arm of the complex, and the myristoyl group may attach
      subunit B18 to the membrane. One subunit, B12, has a particularly complex pattern
      of post-translational modification that has not been analyzed before. It is a
      mixture of the N-alpha-acetylated form and the form with a free N terminus. In
      addition, it has one, two, or three methyl groups attached to histidine residues
      at positions 4, 6, and 8 in various combinations. The predominant form is
      methylated on residues 4 and 6. There is no evidence for the methylation of
      histidine 2. Subunit B12 is also part of the membrane arm of complex I, and it
      probably spans the membrane once, but as its orientation is not known, the
      methylation sites could be in either the matrix or the intermembrane space. These
      experiments represent another significant step toward establishing the precise
      chemical composition of mammalian complex I.

PMID- 15728261
TI  - Superagonistic action of 14-epi-analogs of 1,25-dihydroxyvitamin D explained by
      vitamin D receptor-coactivator interaction.
AB  - Two 14-epi-analogs of 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D(3)], 19-nor-14-epi
      23-yne-1,25-(OH)2D3 (TX522) and 19-nor-14,20-bisepi-23-yne-1,25-(OH)2D3 (TX527),
      show enhanced antiproliferative (at least 10-fold) and markedly lower calcemic
      effects both in vitro and in vivo, compared with 1,25-(OH)2D3. This study aimed
      to evaluate their superagonistic effect at the level of interaction between the
      Vitamin D receptor (VDR) and coactivators. Mammalian two-hybrid assays with VP16
      fused VDR and GAL4-DNA-binding-domain-fused steroid receptor coactivator 1 (SRC
      1), transcriptional intermediary factor 2 (Tif2), or DRIP205 showed the 14-epi
      analogs to be more potent inducers of VDR-coactivator interactions than 1,25
      (OH)2D3 (up to 16- and 20-fold stronger induction of VDR-SRC-1 interaction for
      TX522 and TX527 at 10(-10) M). Similar assays in which metabolism of 1,25-(OH)2D3
      was blocked with VID400, a selective inhibitor of the 1,25-(OH)2D3-metabolizing
      enzyme CYP24, showed that the enhanced potency of these analogs in establishing
      VDR-coactivator interactions can only partially be accounted for by their
      increased resistance to metabolic degradation. Crystallization of TX522 complexed
      to the ligand binding domain of the human VDR demonstrated that the epi
      configuration of C14 caused the CD ring of the ligand to shift by 0.5 angstroms,
      thereby bringing the C12 atom into closer contact with Val300. Moreover, C22 of
      TX522 made an additional contact with the CD1 atom of Ile268 because of the
      rigidity of the triple bond-containing side chain. The position and conformation
      of the activation helix H12 of VDR was strictly maintained. In conclusion, this
      study provides deeper insight into the docking of TX522 in the LBP and shows that
      stronger VDR-coactivator interactions underlie the superagonistic activity of the
      two 14-epi-analogs.

PMID- 15728262
TI  - The general anesthetic isoflurane depresses synaptic vesicle exocytosis.
AB  - General anesthetics have marked effects on synaptic transmission, but the
      mechanisms of their presynaptic actions are unclear. We used quantitative laser
      scanning fluorescence microscopy to analyze the effects of the volatile
      anesthetic isoflurane on synaptic vesicle cycling in cultured neonatal rat
      hippocampal neurons monitored using either transfection of a pH-sensitive form of
      green fluorescent protein fused to the luminal domain of VAMP (vesicle-associated
      membrane protein), (synapto-pHluorin) or vesicle loading with the fluorescent dye
      FM 1-43. Isoflurane reversibly inhibited action potential-evoked exocytosis over
      a range of concentrations, with little effect on vesicle pool size. In contrast,
      exocytosis evoked by depolarization in response to an elevated extracellular
      concentration of KCl, which is insensitive to the selective Na+ channel blocker
      tetrodotoxin, was relatively insensitive to isoflurane. Inhibition of exocytosis
      by isoflurane was resistant to bicuculline, indicating that this presynaptic
      effect is not caused by the well known GABA(A) receptor modulation by volatile
      anesthetics. Depression of exocytosis was mimicked by a reduction in stimulus
      frequency, suggesting a reduction in action potential initiation, conduction, or
      coupling to Ca2+ channel activation. There was no evidence for a direct effect on
      endocytosis. The effects of isoflurane on synaptic transmission are thus caused
      primarily by inhibition of action potential-evoked synaptic vesicle exocytosis at
      a site upstream of Ca2+ entry and exocytosis, possibly as a result of Na+ channel
      blockade and/or K+ channel activation, with the possibility of lesser
      contributions from Ca2+ channel blockade and/or soluble N-ethylmaleimide
      sensitive factor attachment protein receptor-mediated vesicle fusion.

PMID- 15728263
TI  - The stimulatory role of human cytochrome b5 in the bioactivation activities of
      human CYP1A2, 2A6 and 2E1: a new cell expression system to study cytochrome P450
      mediated biotransformation.
AB  - Cytochrome b(5) (b(5)) is increasingly recognized to be of importance for
      specific cytochrome P450 (CYP) activities. We developed human b(5)/CYP-competent
      mutagenicity tester bacteria to study the role of b(5) in the bioactivation
      activity of human CYP. These new tester bacteria were derived from the previously
      engineered human CYP-competent Escherichia coli K12 tester strain MTC, containing
      a bi-plasmid system for the co-expression of a specific CYP form (CYP1A2, 2A6 or
      2E1) with human b(5), and human NADPH cytochrome P450 reductase (RED), resulting
      in the strain BTC-b(5)-1A2, BTC-b(5)-2A6 and BTC-b(5)-2E1, respectively. The
      relative content of b(5) with CYP and RED in these three BTC-b(5)-CYP strains
      demonstrated physiologically relevant co-expression levels and typical CYP
      specific activities could be determined with their specific chemical probes.
      These strains were applied in mutagenicity assays along with their corresponding
      b(5)-void strains to determine the effect of b(5) on the CYP1A2-, CYP2A6- and
      CYP2E1-mediated bioactivation of several promutagens. For CYP1A2, of the 5
      compounds tested [2-aminoanthracene (2AA), 1-aminopyrene, 6-aminochrysene, 2
      amino-3-methylimidazo(4,5-f)quinoline and 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK)], only the mutagenicity of 2AA was slightly increased (
      approximately 1.5-fold) in the presence of b(5). The CYP2E1- and CYP2A6-dependent
      mutagenicity of N-nitrosodiethylamine increased approximately 3- and 23-fold,
      respectively when the bacteria contained b(5). The CYP2A6-mediated mutagenicity
      of NNK increased approximately 9-fold when co-expressed with b(5). The
      stimulatory effect of b(5) on the bioactivation of N-nitrosodi-n-propylamine was
      most striking. The mutagenicity of this procarcinogen was completely dependent on
      the co-expression of b(5) with CYP2A6 or CYP2E1. This demonstrates the prominent
      role of b(5) in the bioactivation of this carcinogen.

PMID- 15728264
TI  - Skin nodules and acute renal failure, what is the link?

PMID- 15728265
TI  - Statins and progression of renal failure: is a reconsideration of clinical
      practice guidelines justified?

PMID- 15728266
TI  - Parasympathetic neuropathy and LVH.

PMID- 15728267
TI  - Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with
      long-term outcome of minimal-change disease.
AB  - BACKGROUND: Minimal-change nephrotic syndrome (MCNS) has been associated with
      atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS,
      we postulated that IL-13 genetic polymorphisms could influence either
      susceptibility or clinical course of the disease. METHODS: Seventy-two Singapore
      Chinese children with MCNS and 78 normal controls were screened for single
      nucleotide polymorphisms (SNPs) in the IL-13 gene by direct sequencing. Allele
      and genotype frequencies of these SNPs were determined and their relationship
      with different clinical courses was analysed. RESULTS: Six SNPs were identified
      in the 5' promoter, exon 4 and 3' untranslated region (3'UTR). The three SNPs in
      the 3'UTR--4738 (G/A), 4793 (C/A) and 4926 (C/T)--were in tight linkage
      disequilibrium (Delta > or = 0.99). There was no difference in allele or genotype
      frequencies between MCNS children and normal controls. However, there was a
      significantly lower frequency of allele 4738G in those MCNS children who were
      still relapsing after 5 years of follow-up (G = 0.52), compared with those in
      complete remission (G = 0.72; P<0.05) and normal controls (G = 0.69; P<0.05).
      Haplotype analysis showed a significantly higher frequency of the GCC haplotype
      in controls and MCNS patients in complete remission (chi2 = 6.35; P<0.02), while
      the frequency of AAT haplotype was higher in those MCNS children still relapsing
      after 5 years of follow-up (chi2 = 5.38; P<0.02). Moreover, peripheral blood
      mononuclear cell IL-13 mRNA expression in patients with haplotype AAT was
      significantly higher than in those with haplotype GCC. CONCLUSIONS: These results
      suggest that genetic polymorphisms in the 3'UTR of the IL-13 gene correlate with
      long-term outcome of MCNS, rather than disease susceptibility, in Singapore
      Chinese children.

PMID- 15728268
TI  - Methylation of CpG islands: potential relevance for hypertension and kidney
      diseases.

PMID- 15728269
TI  - Do not be misguided by guidelines: the calcium x phosphate product can be a
      Trojan horse.

PMID- 15728270
TI  - Mineral metabolism and haemoglobin concentration among haemodialysis patients in
      the Dialysis Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: Bone and mineral metabolism is abnormal in most chronic haemodialysis
      patients and is associated with a high mortality risk. Because of possible
      pathogenic links between anaemia and intact parathyroid hormone (iPTH), the
      present study evaluated associations of mineral metabolism indicators with
      haemoglobin (Hb). METHODS: Data were collected from 317 facilities (12 089
      haemodialysis patients) in Australia, Belgium, Canada, France, Germany, Italy,
      Japan, New Zealand, Spain, Sweden, the United Kingdom and the United States by
      the Dialysis Outcomes and Practice Patterns Study (DOPPS). The major outcome
      studied was probability of haemodialysis patients having a target Hb, per
      guidelines, of >/=11 g/dl at baseline. Major predictor variables were patient
      characteristics and laboratory markers of mineral metabolism: albumin-corrected
      serum calcium (calcium(Alb)), serum phosphorus (PO(4)) and iPTH. Analyses were
      adjusted for demographics, 15 comorbidity classes, baseline laboratory values,
      body mass index, years on dialysis, erythropoietin dose, vitamin D and catheter
      use, cause of end-stage renal disease and country. RESULTS: The adjusted odds
      ratio (AOR) of having Hb >/=11 g/dl was significantly higher (P<0.0001) in
      patients with higher calcium(Alb) (AOR = 1.32 per 1 mg/dl), higher PO(4) (AOR =
      1.08 per 1 mg/dl) and lower iPTH (AOR = 0.96 per 100 pg/ml). Furthermore, 4 month
      intrapatient changes in Hb concentration were significantly (P<0.0001) related to
      4 month changes in calcium(Alb) (0.17 g/dl Hb rise per 1 mg/dl higher
      calcium(Alb)) and PO(4) (0.11 g/dl Hb rise per 1 mg/dl higher PO(4)). Mean weekly
      recombinant human erythropoietin (rHuEpo) doses were higher for patients with
      high PO(4) or iPTH levels, but lower for patients with calcium(Alb) >9.5 mg/dl,
      after patient mix and Hb concentration adjustments. CONCLUSIONS: The results of
      this study indicate that higher serum calcium(Alb) and PO(4) levels are each
      independently associated with better anaemia control. This relationship is
      independent of vitamin D use, PTH levels and prescribed rHuEpo dose. Despite this
      benefit of better anaemia control at higher serum calcium(Alb) and PO(4)
      concentrations, lower calcium and PO(4) levels, as recommended by the K/DOQI
      guidelines, should still serve as the long-term goal for HD patients in order to
      minimize tissue calcification and mortality risk.

PMID- 15728271
TI  - Renal tubular injury associated with anagrelide use.

PMID- 15728272
TI  - Reduced cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a
      haemodialysis population; do CRP and MMP markers of inflammation reflect this
      finding?

PMID- 15728273
TI  - Patient page. Recovery from dementia: an interesting case.

PMID- 15728274
TI  - Report from the neurology scientific integrity advisor: year 1.

PMID- 15728275
TI  - Migraine and cognitive function: some reassuring news.

PMID- 15728276
TI  - Familial hemiplegic migraine: more than just a headache.

PMID- 15728277
TI  - Western vs optic-spinal MS: two diseases, one treatment?

PMID- 15728278
TI  - Titinopathies: what happens when a big gene mutates in a big family?

PMID- 15728279
TI  - Long-term effects of migraine on cognitive function: a population-based study of
      Danish twins.
AB  - OBJECTIVE: To investigate the cognitive functioning of migraineurs vs
      nonmigraineurs in a large population-based sample of middle-aged twins where
      headache diagnoses were established by neurologists. METHODS: Twins identified
      through the population-based Danish Twin Registry participated in face-to-face
      structured interviews, which included cognitive tests and two previously
      validated questions screening for migraine. Twins who screened positive for
      migraine and their co-twins were invited to participate in a telephone-based
      interview conducted by neurologists, who established headache diagnoses according
      to the International Headache Society criteria. Cognitive scores on fluency,
      digit span, delayed word recall, and symbol digit substitution test were compared
      between migraineurs and nonmigraineurs. Comparisons within monozygotic and
      dizygotic same sex twin pairs discordant for migraine were also performed.
      RESULTS: Of the 1,789 twins who were eligible for inclusion in the present study,
      1,393 (77.8%) were interviewed. A diagnosis of migraine was established in 536
      twins (migraine without aura n = 347; migraine with aura n = 157). Average scores
      on cognitive tests in twins with migraine or one of the migraine subtypes did not
      differ from those of nonmigraineurs in any of the tests. Comparisons within twin
      pairs discordant for migraine produced highly comparable results. Adjustment for
      possible confounders and stratification by cumulated number of lifetime attacks
      did not influence the results. CONCLUSIONS: A lifetime diagnosis of migraine was
      not associated with cognitive deficits in middle-aged subjects.

PMID- 15728280
TI  - 1H-MRS alterations in the cerebellum of patients with familial hemiplegic
      migraine type 1.
AB  - BACKGROUND: About 20% of patients with familial hemiplegic migraine (FHM) develop
      progressive cerebellar signs. Genetic studies have established an association
      with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar
      involvement are largely unknown. OBJECTIVE: To use proton MR spectroscopy (1H
      MRS) to investigate metabolic alterations in the cerebellum as well as cortical
      regions known to be involved in the propagation of migraine aura. METHODS:
      Fifteen CACNA1A mutation carriers from three FHM families and 17 healthy control
      subjects were studied. Eleven patients had clinical signs of cerebellar
      involvement. LCModel fits were used to estimate absolute concentrations of N
      acetyl aspartate (NAA), myo-inositol (mI), glutamate (Glu), choline-containing
      compounds, total creatine, and lactate in the superior cerebellar vermis (SCV),
      parietal cortex, and occipital cortex. To control for atrophy effects, automated
      image segmentation was performed using SPM99. The brain parenchyma fraction (BPF)
      was determined for all three regions. RESULTS: Compared with controls, the brain
      parenchyma fraction (BPF), NAA, and Glu were significantly reduced and mI was
      significantly elevated in the SCV of patients with FHM. In contrast, no
      metabolite alterations were found in supratentorial regions. BPF and NAA in the
      SCV significantly correlated with cerebellar scores, in particular, gait ataxia.
      CONCLUSIONS: The findings suggest that there is a regionally distinct neuronal
      impairment in the superior cerebellar vermis that exceeds macroscopic tissue
      loss. Correlations with clinical scores emphasize the functional relevance of
      localized atrophy (brain parenchyma fraction) and N-acetyl aspartate levels.
      These measures may be useful to monitor disease progression. The observed
      reduction in glutamate may in part reflect impaired glutamatergic
      neurotransmission.

PMID- 15728281
TI  - Cardiovascular risk factors and migraine: the GEM population-based study.
AB  - BACKGROUND: Migraine, particularly with aura, is a risk factor for early-onset
      ischemic stroke. The underlying mechanisms are unknown, but may in part be due to
      migraineurs having an increased risk profile for cardiovascular disease. In this
      study, the authors compare the cardiovascular risk profile of adult migraineurs
      to that of nonmigraineurs. METHODS: Participants (n = 5,755, 48% men, age 20 to
      65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population
      based study in the Netherlands. A total of 620 current migraineurs were
      identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified.
      Controls were 5,135 individuals without lifetime migraine. Measured
      cardiovascular risk factors included blood pressure (BP), serum total and high
      density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and
      the Framingham risk score for myocardial infarction or coronary heart disease
      (CHD) death. RESULTS: Compared to controls, migraineurs were more likely to smoke
      (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to
      0.7]), and more likely to report a parental history of early myocardial
      infarction. Migraineurs with aura were more likely to have an unfavorable
      cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio
      > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or
      diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early
      onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were
      more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds
      of having an elevated Framingham risk score for CHD were approximately doubled
      for the migraineurs with aura. CONCLUSIONS: Migraineurs, particularly with aura,
      have a higher cardiovascular risk profile than individuals without migraine.

PMID- 15728282
TI  - Interferon beta-1b is effective in Japanese RRMS patients: a randomized,
      multicenter study.
AB  - OBJECTIVE: To assess the efficacy of interferon beta-1b (IFNB-1b) in Japanese
      patients with relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: The
      effects of IFNB in RRMS have been assessed in study populations comprised
      predominantly of white patients. MS in Japanese patients is different from that
      in white patients in that there are two different presentations--classic MS (C
      MS) and optic-spinal MS (OS-MS)--and chronic progressive forms are infrequent.
      METHODS: A total of 205 Japanese patients with RRMS were randomized to receive 50
      microg or 250 microg (1.6 or 8.0 MIU) IFNB-1b administered SC every other day for
      up to 2 years. The primary endpoint was annual relapse rate. Secondary endpoints
      included further relapse-related and MRI outcome measures, as well as changes in
      Expanded Disability Status Scale and Neurologic Rating Scale. Efficacy was
      assessed in 188 patients, and safety was assessed in 192 patients. Supplemental
      ad hoc subgroup analyses were also performed for patients with OS-MS and those
      with C-MS. RESULTS: Annual relapse rates were 0.763 in the 250 microg group and
      1.069 in the 50 microg group, a relative reduction of 28.6% (p = 0.047). Results
      for all secondary endpoints favored 250 microg IFNB-1b. Subgroup analyses
      suggested that the magnitude and direction of treatment effect in patients with
      OS-MS and C-MS was similar, albeit not significant due to small sample size.
      CONCLUSIONS: Interferon beta-1b (IFNB-1b) 250 microg significantly reduced
      relapse rates and change in MRI lesion area in Japanese patients with relapsing
      remitting multiple sclerosis, and seemed to be comparably effective in optic
      spinal multiple sclerosis (MS) and classic MS. The response to treatment with
      IFNB-1b in Japanese patients with MS suggests that a common pathogenesis and
      underlying genetic characteristics are shared with white patients.

PMID- 15728283
TI  - Quantification of cervical cord pathology in primary progressive MS using
      diffusion tensor MRI.
AB  - OBJECTIVE: To investigate the extent and severity of cervical cord damage using
      diffusion tensor MRI (DT-MRI) and histogram analysis in patients with primary
      progressive MS (PPMS). METHODS: Diffusion-weighted sensitivity-encoded (SENSE)
      echoplanar images of the cervical cord and brain dual-echo and diffusion-weighted
      scans were acquired from 24 patients with PPMS and 13 healthy controls. Cord and
      brain mean diffusivity and fractional anisotropy histograms were produced. An
      analysis of variance model, adjusting for cord volume, was used to compare cord
      DT-MRI parameters from controls and patients. RESULTS: Compared to healthy
      controls, PPMS patients had reduced cervical cord cross-sectional area and
      average cord fractional anisotropy (p = 0.007), and increased cord mean
      diffusivity (p = 0.024). No correlations were found between DT-MRI metrics of the
      cord and quantities obtained from conventional and DT-MRI of the brain.
      CONCLUSIONS: DT-MRI of the cervical cord can quantify the extent of diffuse cord
      pathology in patients with PPMS. Such cord diffusivity changes in patients with
      PPMS are likely to reflect irreversible axonal injury and reactive gliosis and
      seem to be independent of brain damage.

PMID- 15728284
TI  - Titinopathies and extension of the M-line mutation phenotype beyond distal
      myopathy and LGMD2J.
AB  - OBJECTIVE: To determine the phenotype variability associated with the specific C
      terminal M-line titin mutation known to cause autosomal dominant distal myopathy,
      tibial muscular dystrophy (TMD; MIM 600334), and limb girdle muscular dystrophy
      2J (LGMD2J). METHODS: Three hundred eighty-six individuals were genotyped for the
      Finnish founder mutation in titin (FINmaj) causing TMD/LGMD2J. RESULTS: Two
      hundred seven patients were heterozygous for the mutation. Among these patients,
      189 (91%) had a more common phenotype compatible with the classic description of
      TMD. However, 18 (9%) had unusual phenotypes such as proximal leg or posterior
      lower leg muscle weakness and atrophy even at onset. Four patients were confirmed
      homozygotes representing the LGMD2J phenotype. These homozygotes were half of the
      eight LGMD patients previously described in the original large consanguineous
      kindred. CONCLUSIONS: Large variability of phenotypic expression caused by just
      one mutation, the Finnish FINmaj, suggests that no certain phenotype of
      myopathy/dystrophy can be excluded from being caused by mutated titin. Yet
      unknown homozygous or compound heterozygous titin mutations without phenotype in
      the heterozygote carriers may be responsible for undetermined recessive MD and
      LGMD.

PMID- 15728285
TI  - Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.
AB  - BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt
      Jakob disease (sCJD) has been established except for pathologic examination.
      OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type
      sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight
      patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western
      blot analyses. RESULTS: The eight cases were pathologically classified into the
      cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms.
      The cortical form was characterized by late-onset, slowly progressive dementia,
      cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and
      elevated levels of CSF 14-3-3 protein. The thalamic form showed various
      neurologic manifestations including dementia, ataxia, and pyramidal and
      extrapyramidal signs with onset at various ages and relatively long disease
      duration. Characteristic EEG and MRI abnormalities were almost absent. However,
      all four patients examined with cerebral blood flow (CBF) study using SPECT
      showed reduction of the CBF in the thalamus as well as the cerebral cortex. The
      combined form had features of both the cortical and the thalamic forms, showing
      cortical hyperintensity signals on DWI and hypometabolism of the thalamus on
      [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of
      MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on
      diffusion-weighted MRI are useful for the cortical form and thalamic
      hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2
      deoxy-d-glucose PET for the thalamic form.

PMID- 15728286
TI  - The neuropathology of hereditary congenital facial palsy vs Mobius syndrome.
AB  - OBJECTIVE: To characterize the neuropathology of hereditary congenital facial
      palsy. METHODS: The authors compared brainstem pathology of three members of one
      family with autosomal dominant congenital facial palsy to that in three age
      matched controls. The neuropathologic findings of the familial patients were
      compared with those of patients with Mobius syndrome. RESULTS: The authors
      observed a marked decrease in the number of neurons in the facial motor nucleus
      with corresponding small facial nerve remnants. In the patients with congenital
      facial palsy the number of facial motoneurons ranged between 280 and 1,680 as
      compared to 5,030 and 8,700 for controls. No signs of neuronal degeneration or
      necrosis with neuronal loss, gliosis, or calcifications were present. There were
      no other abnormalities of the rhombencephalon and its associated structures. The
      corticospinal tracts were fully developed. In contrast, Mobius syndrome is part
      of a more complex congenital anomaly of the posterior fossa with hypoplasia of
      the entire brainstem, including the traversing long tracts, with signs of
      neuronal degeneration and other congenital brain abnormalities. CONCLUSION:
      Neuropathologic findings confirm clinical observations that hereditary congenital
      facial palsy and Mobius syndrome are two different entities with a different
      pathogenesis.

PMID- 15728287
TI  - Prioritizing interventions to improve rates of thrombolysis for ischemic stroke.
AB  - BACKGROUND: Thrombolytic treatment has been shown to be effective in the
      treatment of ischemic stroke when initiated within 3 hours of symptom onset, yet
      few patients receive thrombolytics. OBJECTIVE: To estimate expected increases in
      use of thrombolytics for ischemic stroke given the following interventions:
      educating patients to present earlier, optimizing Emergency Medical Services
      (EMS) response/transport times, optimizing hospital systems, and extending the
      treatment window. METHODS: As part of a Centers for Disease Control-sponsored
      Coverdell Acute Stroke Pilot Registry, the authors prospectively identified all
      patients with an initial diagnosis of ischemic stroke at 11 hospitals in
      California over a 3-month period. Timing of symptom onset, EMS response, hospital
      arrival, treatment, and reasons for nontreatment were evaluated, and hypothetical
      treatment rates for thrombolysis for interventions on the stroke-care continuum
      were derived based on observed rates of eligibility and treatment. RESULTS: Of
      374 patients with ischemic stroke, 88 (23.5%) arrived at the emergency department
      within 3 hours of symptom onset, of whom 16 (4.3%) received thrombolysis. If all
      patients with known onset times had called 911 immediately, the expected overall
      rate of thrombolytic treatment within 3 hours would have increased from 4.3 to
      28.6%. Expected rates of thrombolysis were lower for other interventions:
      instantaneous prehospital response 5.5%, perfect hospital care 11.5%, and
      extension of time window to 6 hours 8.3%. If all patients with known onset had
      arrived within 1 hour and been optimally treated, 57% could have been treated.
      CONCLUSION: Campaigns that educate patients to seek treatment sooner should be
      major components of system-wide interventions to increase rates of thrombolysis
      for acute ischemic stroke.

PMID- 15728288
TI  - Post-varicella arteriopathy of childhood: natural history of vascular stenosis.
AB  - OBJECTIVE: To determine the course of vascular changes in childhood post
      varicella arteriopathy (PVA) and its relationship to recurrent arterial ischemic
      stroke or TIA (AIS/TIA). METHODS: Subjects were children with AIS/TIA occurring
      <1 year after varicella, ischemic localization consistent with unilateral disease
      affecting the supraclinoid internal carotid artery or proximal anterior or middle
      cerebral arteries, and no identified AIS/TIA etiology other than PVA. Charts,
      brain MRI, and sequential cerebral vessel imaging (selective cerebral angiography
      or MR angiography [SCA/MRA]) were retrospectively reviewed. RESULTS: Twenty-three
      children had varicella at age 1.0 to 10.4 years and had single or multiple
      AIS/TIAs 4 to 47 weeks later. Initial SCA/MRA was performed within 1 month of
      presentation, and each child had one to five repeat SCA/MRAs during a 4- to 87
      month period. There was vascular stenosis in 19 children, maximal on initial
      studies in 15 of these. Subsequent stenosis regression occurred in 17 children.
      In 11 of these, one or two additional SCA/MRAs showed further regression as long
      as 48 months after presentation; there was no restenosis. Eight of 23 children
      had recurrent AIS/TIA with antithrombotic therapy within 33 weeks of
      presentation, including 1 of 17 children with documented stenosis regression.
      CONCLUSION: Vascular stenosis of childhood post-varicella arteriopathy takes a
      monophasic course, generally with subsequent stenosis regression and only
      occasional stenosis progression after arterial ischemic stroke/TIA. Arterial
      ischemic stroke/TIA rarely recurs with antithrombotic prophylaxis after stenosis
      regression occurs.

PMID- 15728289
TI  - Physical activity and the risk of Parkinson disease.
AB  - OBJECTIVE: To investigate whether greater physical activity is associated with a
      lower risk of Parkinson disease (PD). METHODS: The authors prospectively followed
      48,574 men and 77,254 women who provided information on physical activity in 1986
      or in early adulthood. During the follow-up, a total of 252 (male) and 135
      (female) incident PD cases were identified. RESULTS: In men, greater baseline
      physical activity was associated with a lower PD risk; compared with the lowest
      quintile, the multivariate relative risk (RR) of PD for the highest quintile was
      0.7 (95% CI 0.5 to 1.1; p value, test for trend = 0.007), and the inverse
      association was still present after excluding the first 10 years of follow-up (RR
      = 0.5; p value, test for trend = 0.02). Further, strenuous exercise in early
      adult life was also inversely related to PD risk in men: compared with men who
      regularly exercised < or =2 months/year, those with > or =10 months of strenuous
      exercise had a 60% lower PD risk (RR = 0.4; p value, test for trend = 0.005). In
      women, physical activity assessed at baseline was not related to PD risk, whereas
      strenuous exercise in early adulthood tended to be inversely related to PD risk
      later in life (highest vs lowest categories, RR = 0.5, 95% CI 0.2 to 1.4; p
      value, test for trend = 0.06). CONCLUSION: This study suggests either that higher
      levels of physical activity may lower the risk of Parkinson disease (PD) in men
      or that men predisposed to PD tend to avoid strenuous physical activity in their
      early adult years.

PMID- 15728290
TI  - "Off" gait freezing and temporal discrimination threshold in patients with
      Parkinson disease.
AB  - OBJECTIVE: To investigate the relationship between temporal discrimination
      threshold (TDT) and "off" period gait freezing (OGF) in patients with fluctuating
      Parkinson disease (PD). METHODS: TDT values were measured at the dorsum of the
      toes in 11 control subjects and 22 patients with PD with a wearing-off phenomenon
      (16 patients with OGF and 6 patients without OGF). RESULTS: During the l-dopa
      "off" period, TDT values increased abnormally in both patient groups but were
      significantly higher in patients with OGF than in those without OGF. A positive
      correlation was found between the severity of OGF and TDT values measured by
      different point stimulation. In patients with OGF, a single dose of l-dopa
      treatment normalized TDT values and ameliorated OGF. CONCLUSIONS: Dopa-responsive
      abnormal discriminative sensory processing may be a possible cause of "off"
      period gait freezing observed in patients with fluctuating Parkinson disease.

PMID- 15728291
TI  - Quantitative MRI measurement of superior cerebellar peduncle in progressive
      supranuclear palsy.
AB  - BACKGROUND: Postmortem studies have shown atrophy of the superior cerebellar
      peduncle (SCP) to distinguish progressive supranuclear palsy (PSP) from other
      neurodegenerative diseases. It is not clear whether MRI-based measurements can
      differentiate this relative atrophy of the SCP during life. METHODS: Volumetric
      MRI was acquired prospectively in 53 subjects: 19 with PSP, 10 with multiple
      system atrophy (MSA), 12 with Parkinson disease (PD), and 12 healthy controls.
      SCP volume was assessed by detailed quantitative volumetric measurement and
      independently by blinded visual rating of SCP atrophy. RESULTS: The mean SCP
      volume, corrected for total intracranial volume, was lower in patients with PSP
      than controls (p < 0.001), patients with MSA (p = 0.001), and patients with PD (p
      = 0.003). There was an overlap between individual SCP volume measurements in the
      PSP subjects and the other groups. Neuroradiologic rating correctly identified
      PSP cases based on the presence of SCP atrophy with a sensitivity of 74% and a
      specificity of 94%. CONCLUSIONS: The authors propose that together with other
      radiologic features of progressive supranuclear palsy (PSP) such as midbrain
      atrophy, a visual assessment of the superior cerebellar peduncle may help
      increase the clinical diagnostic accuracy in PSP.

PMID- 15728292
TI  - Obtaining a driver's license and seizure relapse in patients with childhood-onset
      epilepsy.
AB  - OBJECTIVE: To examine factors influencing obtaining a driver's license and
      subsequent prognosis among people with epilepsy vs control subjects. METHODS:
      Eighty-one patients from a population-based cohort with childhood-onset epilepsy,
      followed prospectively for 45 years, and 96 general population control subjects
      were compared with regard to driving licensing, seizure relapses, and accidents.
      RESULTS: By the end of the follow-up period, all 81 subjects had achieved at
      least one 2-year seizure-free interval in adulthood and were eligible for a
      driver's license. Of these, 64 vs 90% of control subjects had obtained a license
      (p < 0.0001). On multivariable analysis, factors associated with not obtaining a
      driver's license among subjects were female gender (relative risk [RR] 2.4, 95%
      CI 1.0 to 5.5, p = 0.02), nonidiopathic etiology (RR 2.0, 95% CI 1.1 to 3.8, p =
      0.02), and presence of learning disabilities (RR 2.0, 95% CI 1.2 to 3.2, p =
      0.02). Having a driver's license was associated with a higher rate of employment
      (RR 1.9, 95% CI 1.2 to 3.0, p = 0.0002). Relapses of seizures had occurred in 37%
      of the 81 patients theoretically eligible for a license but only in 25% of the 52
      subjects who actually obtained one (p = 0.003). Shortening the eligibility period
      from 2 to 1 year would not significantly alter the relapse rate in this
      population. The accident rate was not increased among patients vs control
      subjects. CONCLUSIONS: During a long-term follow-up, differences in driving
      licensing between patients with uncomplicated epilepsy and healthy control
      subjects persist despite legal eligibility. The lower actual relapse rates among
      those with epilepsy who obtain a license than in those who are eligible suggest
      that those at higher risk of relapse are less likely to obtain a license.

PMID- 15728293
TI  - Independent accumulations of tau and amyloid beta-protein in the human entorhinal
      cortex.
AB  - BACKGROUND: Previous studies have repeatedly described that neurofibrillary
      tangles arise earlier than senile plaques (SPs) in the entorhinal cortex, but one
      study suggested that SPs, if present, enhance the former lesions. All of these
      studies were performed at the histologic or immunocytochemical level, which may
      not accurately reflect the actual levels of amyloid beta-protein (Abeta) and tau.
      OBJECTIVE: To determine whether there is significant interaction between Abeta
      and tau in the human entorhinal cortex with regard to the Braak stage. METHODS:
      Biochemical studies were conducted on 50 brains from elderly people, who were
      mainly at Braak stages I to III. All the cases were examined neuropathologically
      and staged according to Braak and Braak. A small piece of brain tissue for each
      case was dissected from the anterior portion of the right entorhinal cortex. The
      amounts of tau and Abeta in the insoluble fraction of the tissue were quantified
      using western blotting. RESULTS: The levels of tau and possibly Abeta42 in the
      entorhinal cortex appeared to rise steeply at approximately age 75. The levels of
      insoluble tau increased as the Braak stage increased from I to II; however, it
      had a tendency to remain between stages II and III. The levels of Abeta42 showed
      a small increase, whereas those of Abeta40 increased continuously as the Braak
      stage advanced. In contrast, the extent of Abeta42 accumulation increased with
      increasing Braak stage for SPs. There was no significant correlation between the
      levels of insoluble tau and Abeta42 in the entorhinal cortex. Even if Abeta did
      not accumulate to significant extents, substantial accumulation of insoluble tau
      occurred. CONCLUSION: Accumulations of tau and amyloid beta-protein occur
      independently in the human entorhinal cortex.

PMID- 15728294
TI  - Unawareness of cognitive deficit (cognitive anosognosia) in probable AD and
      control subjects.
AB  - OBJECTIVE: To develop a quantitative method of assessing cognitive anosognosia in
      six cognitive and two noncognitive domains. METHODS: Control (n = 32) and
      probable Alzheimer disease (pAD) (n = 14) subjects self-estimated memory,
      attention, generative behavior, naming, visuospatial skill, limb praxis, mood,
      and uncorrected vision, both before and after these abilities were assessed.
      Based on this estimate and their performance the authors calculated an
      anosognosia ratio (AR) by dividing the difference between estimated and actual
      performance by an estimated and actual performance sum. With perfect awareness,
      AR = 0. Overestimating abilities would yield a positive AR (< or =1);
      underestimation would yield a negative AR (> or =-1). RESULTS: Relative to
      controls, pAD subjects demonstrated anosognosia. Pre-testing (off-line), pAD
      subjects overestimated their visuospatial skill; post-testing (on-line), pAD
      subjects overestimated their memory. Control subjects also made self-rating
      errors, underestimating their attention pre-testing and overestimating limb
      praxis and vision post-testing. CONCLUSIONS: This anosognosia assessment method
      may allow more detailed examination of distorted self-awareness. These results
      suggest that screening for anosognosia in probable Alzheimer disease (pAD) should
      include self-estimates of visuospatial function, and that, in pAD, it may be
      useful to assess anosognosia for amnesia both before and after memory testing.

PMID- 15728295
TI  - fMRI reveals two distinct cerebral networks subserving speech motor control.
AB  - BACKGROUND: There are few data on the cerebral organization of motor aspects of
      speech production and the pathomechanisms of dysarthric deficits subsequent to
      brain lesions and diseases. The authors used fMRI to further examine the neural
      basis of speech motor control. METHODS AND RESULTS: In eight healthy volunteers,
      fMRI was performed during syllable repetitions synchronized to click trains (2 to
      6 Hz; vs a passive listening task). Bilateral hemodynamic responses emerged at
      the level of the mesiofrontal and sensorimotor cortex, putamen/pallidum,
      thalamus, and cerebellum (two distinct activation spots at either side). In
      contrast, dorsolateral premotor cortex and anterior insula showed left-sided
      activation. Calculation of rate/response functions revealed a negative linear
      relationship between repetition frequency and blood oxygen level-dependent (BOLD)
      signal change within the striatum, whereas both cerebellar hemispheres exhibited
      a step-wise increase of activation at approximately 3 Hz. Analysis of the
      temporal dynamics of the BOLD effect found the various cortical and subcortical
      brain regions engaged in speech motor control to be organized into two separate
      networks (medial and dorsolateral premotor cortex, anterior insula, and superior
      cerebellum vs sensorimotor cortex, basal ganglia, and inferior cerebellum).
      CONCLUSION: These data provide evidence for two levels of speech motor control
      bound, most presumably, to motor preparation and execution processes. They also
      help to explain clinical observations such as an unimpaired or even accelerated
      speaking rate in Parkinson disease and slowed speech tempo, which does not fall
      below a rate of 3 Hz, in cerebellar disorders.

PMID- 15728296
TI  - Steroid dementia: an overlooked diagnosis?
AB  - The authors studied a 72-year-old man with polymyalgia rheumatica who, after
      taking 100 mg of prednisone for 3 months, developed a psychosis followed by
      dementia. It was initially considered that the dementia was a separate
      neurodegenerative condition, probably of Alzheimer type, but when steroids were
      discontinued, he rapidly returned to his previous level of functioning. Reviewing
      the literature regarding the effects of steroids on cerebral function, the
      authors found that such cases of "reversible dementia" are not uncommon, although
      rarely given the emphasis they deserve. The authors believe, given the extensive
      use of steroids in medical practice, that physicians should be more aware of this
      important cause of reversible dementia.

PMID- 15728297
TI  - L-arginine improves the symptoms of strokelike episodes in MELAS.
AB  - Based on the hypothesis that mitochondrial myopathy, encephalopathy, lactic
      acidosis, and strokelike episodes (MELAS) are caused by impaired vasodilation in
      an intracerebral artery, the authors evaluated the effects of administering l
      arginine, a nitric oxide precursor. Patients were administered L-arginine
      intravenously at the acute phase or orally at the interictal phase. L-arginine
      infusions significantly improved all strokelike symptoms, suggesting that oral
      administration within 30 minutes of a stroke significantly decreased frequency
      and severity of strokelike episodes.

PMID- 15728298
TI  - Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial.
AB  - Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10),
      is effective in migraine prophylaxis. We compared CoQ10 (3 x 100 mg/day) and
      placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled
      trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days
      with-nausea in the third treatment month and well tolerated; 50%-responder-rate
      for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to
      treat: 3). CoQ10 is efficacious and well tolerated.

PMID- 15728299
TI  - A topodiagnostic investigation on body lateropulsion in medullary infarcts.
AB  - Body lateropulsion may occur without signs of vestibular dysfunction and
      vestibular nucleus involvement. The authors examined 10 such patients with three
      dimensional brainstem mapping. Body lateropulsion without limb ataxia reflected
      an impairment of vestibulospinal postural control caused by a lesion of the
      descending lateral vestibulospinal tract, whereas body lateropulsion with limb
      ataxia was probably the consequence of impaired or absent proprioceptive
      information caused by a lesion of the ascending dorsal spino-cerebellar tract.

PMID- 15728300
TI  - Reasons for exclusion from thrombolytic therapy following acute ischemic stroke.
AB  - Despite evidence for the efficacy of thrombolytic therapy in acute ischemic
      stroke, only 1 to 7% of patients receive this therapy. The authors sought to
      determine the reasons for exclusion from tissue plasminogen activator (tPA) in an
      acute setting and found avoidable causes in 18% of patients. Improvements in
      intrahospital coordination would increase the number of patients who might
      benefit from tPA treatment at the authors' center.

PMID- 15728301
TI  - The impact of privacy protections on recruitment in a multicenter stroke genetics
      study.
AB  - The authors reviewed the recruitment of stroke-affected sibling pairs using a
      letter-based, proband-initiated contact strategy. The authors randomly sampled 99
      proband enrollment forms (Phase 1) and randomly sampled 50 sibling reply cards
      (Phase 2). The sibling response rate was 30.6%, for a pedigree response rate of
      58%. Of the siblings who replied, 96% authorized further contact. Median time
      from proband enrollment to pedigree DNA banking, which required 3+ probands, was
      134 days.

PMID- 15728302
TI  - Early mortality following spontaneous intracerebral hemorrhage.
AB  - The authors reviewed the charts of 1,421 patients with cerebral hemorrhage to
      determine the cause of death. Limitation or withdrawal of life-sustaining
      interventions was the most common cause of death (68%) followed by brain death
      (28%). Neurologic reasons were the most common cause of delayed decisions to
      withdraw or limit therapy. Brain death was more common in African Americans,
      whereas life-sustaining interventions were withdrawn or limited early more often
      in whites.

PMID- 15728303
TI  - Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility
      study.
AB  - Ketones may bypass the defect in complex I activity implicated in Parkinson
      disease (PD). Five of seven volunteers with PD were able to prepare a
      "hyperketogenic" diet at home and adhere to it for 28 days. Substituting
      unsaturated for saturated fats appeared to prevent cholesterol increases in four
      volunteers. Unified Parkinson's Disease Rating Scale scores improved in all five
      during hyperketonemia, but a placebo effect was not ruled out.

PMID- 15728304
TI  - Young onset limb spasticity with PSP-like brain and spinal cord NFT-tau
      pathology.
AB  - A 30-year-old white man presented with a sporadic form of gradually progressive
      spastic gait and, later, supranuclear vertical and horizontal gaze palsy, mild
      cognitive impairment, loss of postural reflexes, and falls. DNA analysis revealed
      H1/H1 haplotype without tau gene (exons 9 to 13) mutation. Eight years later,
      postmortem revealed a tauopathy similar to progressive supranuclear palsy.
      Unusual aspects were early age at onset, neurofibrillary tangle, and tau
      involvement of the cord.

PMID- 15728305
TI  - Pattern of glucose hypometabolism in frontotemporal dementia with motor neuron
      disease.
AB  - Frontotemporal dementia (FTD) often coexists with motor neuron disease (MND). To
      characterize glucose hypometabolism in patients with FTD with MND (FTD/MND), the
      authors compared the glucose metabolism of 8 patients with FTD/MND with that of
      29 patients with FTD. All of the patients with FTD/MND showed glucose
      hypometabolism only in the frontal area, whereas most patients with FTD had
      hypometabolism in the frontal and temporal areas. FTD/MND also showed a more
      symmetric pattern of glucose hypometabolism than FTD.

PMID- 15728306
TI  - The epsilon-sarcoglycan gene in myoclonic syndromes.
AB  - Mutations in the epsilon-sarcoglycan gene (SGCE) are associated with familial
      myoclonus dystonia, but the full spectrum of the phenotype may not be fully
      defined. We screened 58 individuals with a range of myoclonic/dystonic syndromes
      for SGCE mutations. We found mutations (three of them novel) in six (21%) of the
      29 patients with essential myoclonus and myoclonic dystonia, but did not find
      mutations in the 29 patients with other phenotypes.

PMID- 15728307
TI  - A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile
      onset.
AB  - Three related patients from Colombia presented with a juvenile-onset neuronal
      ceroid lipofuscinosis. Electron microscopy of one case showed condensed
      fingerprint profiles, and genetic analyses identified a novel missense mutation
      in CLN5. The authors demonstrate the existence of pathogenic CLN5 mutations
      outside northern Europe and that mutations in this gene can lead to an atypical
      late-onset neuronal ceroid lipofuscinosis disease, in addition to the late
      infantile form first described in Finland.

PMID- 15728309
TI  - Surgery for symptomatic infant-onset epileptic encephalopathy with and without
      infantile spasms.
AB  - Children undergoing surgery with infant-onset epilepsy were classified into those
      with medically refractory infantile spasms (IS), successfully treated IS, and no
      IS history, and the groups were compared for pre- and postsurgery clinical and
      Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ). Children
      without an IS history were older at surgery and had longer epilepsy durations
      than those with IS despite similar substrates, surgeries, and seizure
      frequencies. In all groups, better postsurgery VABS-DQ scores were associated
      with early surgical intervention indicating that infant-onset epilepsy patients
      with or without IS are at risk for seizure-induced encephalopathy.

PMID- 15728310
TI  - MRI in biopsy-negative dermatomyositis.

PMID- 15728308
TI  - Autoimmunity to glutamic acid decarboxylase in the neurodegenerative disorder
      Batten disease.
AB  - The pathogenic mechanisms underlying Batten disease are unclear. Patients
      uniformly possess autoantibodies against glutamic acid decarboxylase (GAD) that
      are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct
      from subjects with autoimmune type 1 diabetes or stiff-person syndrome. Batten
      patients did not possess autoantibodies against other type 1 diabetes-associated
      autoantigens and human leukocyte antigen genotypes revealed no specific
      associations with this disease.

PMID- 15728311
TI  - Interlimb coordination deficits during cyclic movements in cerebellar hemiataxia.
AB  - The authors report a 35-year-old man whose unilateral cerebellar lesion resulted
      in marked deficits in coordinating simultaneous cyclic movements of the arm and
      leg on his ipsilesional side. He exhibited no such deficits when making
      simultaneous movements of the contralesional limbs or when moving paired left and
      right limbs. Thus, the cerebellum, which is already known to underlie within-limb
      interjoint coordination, also contributes to coordination between limbs.

PMID- 15728312
TI  - Laryngospasm: an underdiagnosed symptom of X-linked spinobulbar muscular atrophy.
AB  - The authors reviewed the occurrence and concomitant factors of laryngospasm in X
      linked spinobulbar muscular atrophy (Kennedy disease [KD]). Recurrent
      laryngospasm was observed in 47% of 49 patients with KD, but in only 2% of a
      control group of patients with early-stage ALS.

PMID- 15728314
TI  - Ventromedial frontal lobe trauma.

PMID- 15728313
TI  - Cystatin C as a risk factor for Alzheimer disease.
AB  - Cystatin C, a protease inhibitor with widespread distribution, is upregulated in
      response to injury. Levels are elevated in the brains of patients with Alzheimer
      disease (AD). We compared frequencies for the CST 3 exon 1 polymorphism in
      patients with AD and controls. A proportional odds model indicated that the CST 3
      A and APOE4 combination carried a high risk: a 14-fold elevation for men and 16
      fold for women. These risks apply to risk at ages older than 64 years and to a
      shift in onset to ages younger than 65 years.

PMID- 15728315
TI  - Delayed resolution of white matter changes following therapy of B burgdorferi
      encephalitis.

PMID- 15728317
TI  - Left premotor lesion producing selective impairment of habitual finger movement.

PMID- 15728316
TI  - Episodic third nerve palsy with cryptococcal meningitis.

PMID- 15728318
TI  - Spinal cord transient ischemic attacks: a possible role for abciximab.

PMID- 15728319
TI  - Lower stroke-related mortality in counties with stroke centers: North Carolina
      Stroke Facilities Survey.

PMID- 15728321
TI  - Doxycycline and intracranial hypertension.

PMID- 15728320
TI  - Continued use of zonisamide following development of renal calculi.

PMID- 15728322
TI  - MEG localization of language-specific cortex utilizing MR-FOCUSS.

PMID- 15728323
TI  - Does Campylobacter jejuni infection elicit "demyelinating" Guillain-Barre
      syndrome?

PMID- 15728325
TI  - Willisian collateralization.

PMID- 15728324
TI  - Memory impairment, but not cerebrovascular disease, predicts progression of MCI
      to dementia.

PMID- 15728326
TI  - Neuropsychiatric impact of hepatitis C on advanced HIV.

PMID- 15728327
TI  - Antidepressant-induced sweating.
AB  - OBJECTIVE: To report a case of excessive sweating probably caused by paroxetine,
      review the literature on antidepressant-induced sweating, and provide
      recommendations for the management of antidepressant-induced sweating. CASE
      SUMMARY: A 59-year-old white female presented to a pharmacist-staffed
      pharmacotherapy clinic with episodes of excessive sweating. The episodes occurred
      primarily on her head and back of the neck. Other etiologies were ruled out and
      paroxetine was discontinued. Paroxetine had been initiated at least 7 months
      prior to the reporting of symptoms. Sweating symptoms gradually improved until
      resolution 5 weeks following discontinuation of paroxetine. The Naranjo
      probability scale indicated a causal relationship is probable. DISCUSSION:
      Excessive sweating has been associated with antidepressants including tricyclic
      antidepressants, selective serotonin-reuptake inhibitors, and venlafaxine. In
      some patients, these symptoms require therapeutic intervention such as dose
      reduction, antidepressant substitution, antidepressant discontinuation, or
      addition of an agent to control sweating. Agents that have been reported
      successful in controlling the sweating include benztropine and cyproheptadine.
      CONCLUSIONS: We recommend a patient-specific approach for the management of
      antidepressant-induced sweating. First, consider dose reduction or a trial off
      antidepressant medication. In patients in whom this is inappropriate or
      ineffective, substitution of another antidepressant should be considered. If
      episodes of excessive sweating persist, consider treatment of sweating symptoms
      with benztropine or cyproheptadine in the absence of contraindications.

PMID- 15728328
TI  - Anasarca edema with amlodipine treatment.
AB  - OBJECTIVE: To report a case of anasarca edema associated with amlodipine use.
      CASE SUMMARY: A 77-year-old woman with essential hypertension who had not been
      treated with any other drug was prescribed amlodipine 10 mg/day to control her
      blood pressure. She developed anasarca edema soon after amlodipine treatment was
      initiated. Laboratory test results for possible etiologies were negative.
      Discontinuation of amlodipine resulted in dramatic improvement. DISCUSSION: To
      our knowledge, as of February 3, 2005, there have been no other reports of
      amlodipine-related anasarca edema in the English literature, and only one case
      was described in the Japanese literature. Pretibial edema is the most common
      adverse effect of amlodipine. Periocular and perioral edema have occurred less
      frequently, but anasarca edema has not emerged as a problem. An objective
      causality assessment revealed amlodipine to be a probable cause of anasarca
      edema. CONCLUSIONS: In rare instances, amlodipine may cause generalized edema,
      which will resolve upon discontinuation of the drug.

PMID- 15728329
TI  - Glycoprotein IIb/IIIa inhibitors in patients with end-stage renal disease.
AB  - OBJECTIVE: To determine whether glycoprotein IIb/IIIa inhibitors (GPIs) are
      effective and safe as adjunctive therapy for percutaneous coronary intervention
      (PCI) in patients with end-stage renal disease (ESRD). DATA SOURCES: MEDLINE
      (1966-June 2004), EMBASE (1980-June 2004), and International Pharmaceutical
      Abstracts (1970-June 2004) were searched, in addition to a manual bibliographic
      search. DATA SYNTHESIS: Even though GPIs have an established role as adjunctive
      therapy in PCI, little is known about their use in patients with ESRD. We found 3
      reports describing experience with abciximab in this population. Based on the
      limited information from registries and a retrospective chart review, it is
      difficult to draw definitive conclusions about the utility of GPIs in ESRD. The
      decision to use abciximab in this population must be made on an individual case
      basis. CONCLUSIONS: Studies are needed to evaluate the benefit versus risk of GPI
      therapy in ESRD.

PMID- 15728330
TI  - Pharmacists' participation in an inhaled respiratory medication program:
      reimbursement of professional fees.
AB  - BACKGROUND: An intervention (termed Initiative) was initiated to facilitate
      converting beneficiaries of a public drug insurance program in the province of
      Nova Scotia from respiratory nebulization medications to inhalers. Community
      pharmacists provided patient education and billed professional fees for
      conversions or optimizing inhaled respiratory medication technique. OBJECTIVE: To
      determine community pharmacists' self-reported participation rate and identify
      facilitators and barriers to billing for professional fees. METHODS: A survey was
      developed and mailed to Nova Scotia pharmacists. Information on demographics,
      work environment, professional experience, financial aspects, billing
      experiences, and the billing process was collected. Quantitative and qualitative
      data were evaluated using bivariate and multivariate analyses, and a thematic
      process, respectively. RESULTS: Two hundred ninety-seven pharmacists responded.
      Self-reported billing rates for fees were 34% (switching delivery devices), 58%
      (optimizing AeroChamber use), and 37% (follow-up when replacing Aerochambers).
      Awareness of fees and the perception of consistent claim reimbursement were
      associated with billing for each fee (p < 0.05). Predisposing billing factors
      included awareness of fees, identifying situations requiring education,
      owner/manager position, male gender, perception that billing for education for
      optimizing technique is a minimum standard of practice, and prescription volume.
      Themes identified as barriers included inefficient billing process, inadequate
      fees, and lack of Initiative awareness. CONCLUSIONS: Predisposing factors were
      the most important facilitators of community pharmacists' participation in this
      program, while a cumbersome and time-consuming billing process was the primary
      barrier. Further research should determine the impact of the professional fee on
      patient health outcomes.

PMID- 15728331
TI  - Serious psychiatric symptoms after chloroquine treatment following experimental
      malaria infection.
AB  - OBJECTIVE: To report serious psychiatric symptoms after standard chloroquine
      treatment following human malaria infection induced for research. CASE SUMMARY: A
      34-year-old healthy woman volunteered to participate in a study of malaria
      treatment. She was infected on day 0 with a chloroquine-susceptible strain of
      Plasmodium falciparum and was treated with a standard 3-day course of chloroquine
      from day 9 onward, following a positive blood smear (parasitemia 0.001%). On day
      10, the blood smear became negative. On day 11, she developed a psychotic
      disorder not otherwise specified, most probably caused by chloroquine use, with
      symptoms of depersonalization and anxiety. The diagnosis of delirium was
      considered but ruled out because of clear consciousness with lack of diurnal
      fluctuations. She refused to take antipsychotic medication. Three weeks later,
      the woman still encountered serious concentration problems. All complaints
      gradually subsided over the next 4 months, after which she felt completely
      recovered. Plasma chloroquine concentrations were within the therapeutic range.
      DISCUSSION: Chloroquine may achieve high concentrations in the brain and has a
      long half-life. As quinolines, the antimalarials may have the same pathologic
      activity as the fluoroquinolone antibiotics in acting as N-methyl-d-aspartate
      agonists and gamma-aminobutyric acid antagonists. Application of the Naranjo
      probability scale indicated that, in this patient, chloroquine was the probable
      cause of the serious psychiatric symptoms. CONCLUSIONS: Our unique observation
      demonstrates that serious psychiatric symptoms can emerge as a rare occurrence
      during standard chloroquine therapy. This adverse effect may persist for several
      months.

PMID- 15728332
TI  - Tobacco smoke dysregulates endothelial vasoregulatory transcripts in vivo.
AB  - We hypothesized that human smoking and its deleterious effects on endothelial
      function can be modeled by exposure of mice to tobacco smoke, and further that
      these changes would be reflected in gene regulation in vascular endothelium. We
      used for these studies a mouse strain that expresses green fluorescent protein
      under the control of an endothelial-specific promoter, Tie-2. Mice were exposed
      to sidestream smoke from reference cigarettes at 34 mg total suspended
      particulates/m3. After exposure for 5 days/wk for 1 and 6 wk, aortas were pooled
      from treatment and control groups. Endothelial cells were rapidly isolated by
      collagenase treatment followed by fluorescent activated cell sorting to yield
      populations of >95% purity. RNA isolated from >500 endothelial cells was
      amplified and analyzed on deeply representative long oligo microarrays.
      Transcripts dysregulated by >2.5-fold were confirmed by real-time PCR and
      selected proteins by immunofluorescent localization. In the endothelial cells,
      the observed more than threefold upregulation of complement factor H (Cfh),
      calcitonin receptor-like (Calcr1), and soluble epoxide hydrolase (Epxh2) may play
      a role in hypertensive responses of the vasculature to smoking. We have
      identified gene regulation in vivo in vascular endothelium that potentially
      underlies hypertensive responses to tobacco smoke.

PMID- 15728333
TI  - Identification of genes that are differentially expressed in hemocytes of the
      Pacific blue shrimp (Litopenaeus stylirostris) surviving an infection with Vibrio
      penaeicida.
AB  - Considerable progress has been made in the field of invertebrate immunity through
      the characterization of genes involved in the response to infection and/or
      stress. However, the mechanisms by which commercially important marine
      invertebrates can successfully survive an infection remain largely unknown. For
      the first time in an invertebrate model, we have searched to discover genes
      involved in the survival capacity of shrimp using the highly pathogenic bacteria,
      Vibrio penaeicida. In the present study, we applied the technique of suppression
      subtractive hybridization (SSH) to hemocyte cDNAs from infected and uninfected
      shrimp, only using samples from individuals that had survived 96 h postinfection.
      The resulting library contains 260 expressed sequence tagged (EST) cDNA clones
      potentially representing highly expressed genes in surviving shrimp. Sequence
      similarity comparisons were made, and putative identities were assigned to clones
      that were at least 51% identical to known genes. This analysis showed two
      functional categories that were highly represented: those of genes involved in
      immune reactions (10.7% of the ESTs) and those involved in proliferation
      hematopoiesis (10.3%). Expression pattern profile analyses of selected ESTs at
      different times postinfection confirmed the differential expression of the genes
      and efficiency of the SSH method. Differences in gene transcript abundance, for
      select ESTs encoding antimicrobial effectors, were evidenced by real-time PCR
      between shrimp that survived acute Vibrio infection and those individuals that
      did not survive acute Vibrio infection. These results suggest there are basic
      differences at the level of transcript abundance for genes directly involved in
      immune and hematopoietic processes from shrimp that survive and do not survive
      infection.

PMID- 15728334
TI  - Dynamic genetic architecture of metabolic syndrome attributes in the rat.
AB  - The polydactylous rat strain (PD/Cub) is a highly inbred (F > 90) genetic model
      of metabolic syndrome. The aim of this study was to analyze the genetic
      architecture of the metabolic derangements found in the PD/Cub strain and to
      assess its dynamics in time and in response to diet and medication. We derived a
      PD/Cub x BN/Cub (Brown Norway) F2 intercross population of 149 male rats and
      performed metabolic profiling and genotyping and multiple levels of genetic
      linkage and statistical analyses at five different stages of ontogenesis and
      after high-sucrose diet feeding and dexamethasone administration challenges. The
      interval mapping analysis of 83 metabolic and morphometric traits revealed over
      50 regions genomewide with significant or suggestive linkage to one or more of
      the traits in the segregating PD/Cub x BN/Cub population. The multiple interval
      mapping showed that, in addition to "single" quantitative train loci, there are
      more than 30 pairs of loci across the whole genome significantly influencing the
      variation of particular traits in an epistatic fashion. This study represents the
      first whole genome analysis of metabolic syndrome in the PD/Cub model and reveals
      several new loci previously not connected to the genetics of insulin resistance
      and dyslipidemia. In addition, it attempts to present the concept of "dynamic
      genetic architecture" of metabolic syndrome attributes, evidenced by shifts in
      the genetic determination of syndrome features during ontogenesis and during
      adaptation to the dietary and pharmacological influences.

PMID- 15728335
TI  - Microarray analysis reveals pivotal divergent mRNA expression profiles early in
      the development of either compensated ventricular hypertrophy or heart failure.
AB  - Myocardial right ventricular (RV) hypertrophy due to pulmonary hypertension is
      aimed at normalizing ventricular wall stress. Depending on the degree of pressure
      overload, RV hypertrophy may progress to a state of impaired contractile function
      and heart failure, but this cannot be discerned during the early stages of
      ventricular remodeling. We tested whether critical differences in gene expression
      profiles exist between ventricles before the ultimate development of either a
      compensated or decompensated hypertrophic phenotype. Both phenotypes were
      selectively induced in Wistar rats by a single subcutaneous injection of either a
      low or a high dose of the pyrrolizidine alkaloid monocrotaline (MCT). Spotted
      oligonucleotide microarrays were used to investigate pressure-dependent cardiac
      gene expression profiles at 2 wk after the MCT injections, between control rats
      and rats that would ultimately develop either compensated or decompensated
      hypertrophy. Clustering of significantly regulated genes revealed specific
      expression profiles for each group, although the degree of hypertrophy was still
      similar in both. The ventricles destined to progress to failure showed activation
      of pro-apoptotic pathways, particularly related to mitochondria, whereas the
      group developing compensated hypertrophy showed blocked pro-death effector
      signaling via p38-MAPK, through upregulation of MAPK phosphatase-1. In summary,
      we show that, already at an early time point, pivotal differences in gene
      expression exist between ventricles that will ultimately develop either a
      compensated or a decompensated phenotype, depending on the degree of pressure
      overload. These data reveal genes that may provide markers for the early
      prediction of clinical outcome as well as potential targets for early
      intervention.

PMID- 15728336
TI  - Impaired pH homeostasis in Arabidopsis lacking the vacuolar dicarboxylate
      transporter and analysis of carboxylic acid transport across the tonoplast.
AB  - Arabidopsis (Arabidopsis thaliana) mutants lacking the tonoplastic malate
      transporter AttDT (A. thaliana tonoplast dicarboxylate transporter) and wild-type
      plants showed no phenotypic differences when grown under standard conditions. To
      identify putative metabolic changes in AttDT knock-out plants, we provoked a
      metabolic scenario connected to an increased consumption of dicarboxylates.
      Acidification of leaf discs stimulated dicarboxylate consumption and led to
      extremely low levels of dicarboxylates in mutants. To investigate whether reduced
      dicarboxylate concentrations in mutant leaf cells and, hence, reduced capacity to
      produce OH(-) to overcome acidification might affect metabolism, we measured
      photosynthetic oxygen evolution under conditions where the cytosol is acidified.
      AttDT::tDNA protoplasts showed a much stronger inhibition of oxygen evolution at
      low pH values when compared to wild-type protoplasts. Apparently citrate, which
      is present in higher amounts in knock-out plants, is not able to replace
      dicarboxylates to overcome acidification. To raise more information on the
      cellular level, we performed localization studies of carboxylates. Although the
      total pool of carboxylates in mutant vacuoles was nearly unaltered, these
      organelles contained a lower proportion of malate and fumarate and a higher
      proportion of citrate when compared to wild-type vacuoles. These alterations
      concur with the observation that radioactively labeled malate and citrate are
      transported into Arabidopsis vacuoles by different carriers. In addition, wild
      type vacuoles and corresponding organelles from AttDT::tDNA mutants exhibited
      similar malate channel activities. In conclusion, these results show that
      Arabidopsis vacuoles contain at least two transporters and a channel for
      dicarboxylates and citrate and that the activity of AttDT is critical for
      regulation of pH homeostasis.

PMID- 15728337
TI  - Low temperature induction of Arabidopsis CBF1, 2, and 3 is gated by the circadian
      clock.
AB  - Exposing Arabidopsis (Arabidopsis thaliana) plants to low temperature results in
      rapid induction of CBF1, 2, and 3 (CBF1-3; also known as DREB1B, C, and A,
      respectively), which encode transcriptional activators that induce expression of
      a battery of genes that increase plant freezing and chilling tolerance. Recently,
      it has been shown that basal levels of CBF3 transcripts and those of certain CBF
      regulated genes exhibit circadian cycling. Here, we further explored the
      regulation of CBF1-3 by the circadian clock. The results indicated that the
      extent to which CBF1-3 transcripts accumulated in response to low temperature was
      dependent on the time of day that the plants were exposed to low temperature and
      that this was regulated by the circadian clock. The highest and lowest levels of
      cold-induced CBF1-3 transcript accumulation occurred at 4 and 16 h after
      subjective dawn, respectively. An analysis of CBF2 promoter-reporter gene fusions
      indicated that this control included transcriptional regulation. In addition, the
      cold responsiveness of RAV1 and ZAT12, genes that are cold induced in parallel
      with CBF1-3, was also subject to circadian regulation. However, whereas the
      maximum level of cold-induced RAV1 transcript accumulation occurred at the same
      time of day as did CBF1-3 transcripts, that of ZAT12 was in reverse phase, i.e.
      the highest level of cold-induced ZAT12 transcript accumulation occurred 16 h
      after subjective dawn. These results indicate that cold-induced expression of
      CBF1-3, RAV1, and ZAT12 is gated by the circadian clock and suggest that this
      regulation likely occurs through at least two nonidentical (though potentially
      overlapping) signaling pathways.

PMID- 15728339
TI  - Impact of reduced O-acetylserine(thiol)lyase isoform contents on potato plant
      metabolism.
AB  - Plant cysteine (Cys) synthesis can occur in three cellular compartments: the
      chloroplast, cytoplasm, and mitochondrion. Cys formation is catalyzed by the
      enzyme O-acetylserine(thiol)lyase (OASTL) using O-acetylserine (OAS) and sulfide
      as substrates. To unravel the function of different isoforms of OASTL in cellular
      metabolism, a transgenic approach was used to down-regulate specifically the
      plastidial and cytosolic isoforms in potato (Solanum tuberosum). This approach
      resulted in decreased RNA, protein, and enzymatic activity levels. Intriguingly,
      H(2)S-releasing capacity was also reduced in these lines. Unexpectedly, the thiol
      levels in the transgenic lines were, regardless of the selected OASTL isoform,
      significantly elevated. Furthermore, levels of metabolites such as serine, OAS,
      methionine, threonine, isoleucine, and lysine also increased in the investigated
      transgenic lines. This indicates that higher Cys levels might influence
      methionine synthesis and subsequently pathway-related amino acids. The increase
      of serine and OAS points to suboptimal Cys synthesis in transgenic plants. Taking
      these findings together, it can be assumed that excess OASTL activity regulates
      not only Cys de novo synthesis but also its homeostasis. A model for the
      regulation of Cys levels in plants is proposed.

PMID- 15728338
TI  - Topolins and hydroxylated thidiazuron derivatives are substrates of cytokinin O
      glucosyltransferase with position specificity related to receptor recognition.
AB  - Glucosides of trans-zeatin occur widely in plant tissues, formed either by O
      glucosylation of the hydroxylated side chain or N-glucosylation of the purine
      ring structure. O-Glucosylation is stereo-specific: the O-glucosyltransferase
      encoded by the Phaseolus lunatus ZOG1 gene has high affinity for trans-zeatin as
      the substrate, whereas the enzyme encoded by the maize (Zea mays) cisZOG1 gene
      prefers cis-zeatin. Here we show that hydroxylated derivatives of benzyladenine
      (topolins) are also substrates of ZOG1 and cisZOG1. The m-OH and o-OH derivatives
      are the preferred substrate of ZOG1 and cisZOG1, respectively. Among the
      hydroxylated derivatives of thidiazuron tested, the only enzyme/substrate
      combination resulting in conversion was cisZOG1/(o-OH) thidiazuron. The abilities
      of these cytokinins to serve as substrates to the glucosyltransferases were in a
      large part correlated with their biological activities in the P. lunatus callus
      bioassay, indicating that there may be similarities between cytokinin-binding
      sites on the enzymes and cytokinin receptors. Further support for this
      interpretation is provided by cytokinin recognition studies involving the
      Arabidopsis (Arabidopsis thaliana) CRE1/WOL/AHK4 and maize ZmHK1 receptors. The
      AHK4 receptor responded to trans-zeatin and m-topolin, while the ZmHK1 receptor
      responded also to cis-zeatin and o-topolin. Three-dimensional molecular models of
      the substrates were applied to explain the results.

PMID- 15728340
TI  - Salicylic acid-dependent expression of host genes in compatible Arabidopsis-virus
      interactions.
AB  - Plant viruses elicit the expression of common sets of genes in susceptible hosts.
      Studies in Arabidopsis (Arabidopsis thaliana) and tomato (Lycopersicon
      esculentum) indicate that at least one-third of the genes induced in common by
      viruses have been previously associated with plant defense and stress responses.
      The genetic and molecular requirements for the induction of these stress and
      defense-related genes during compatible host-virus interactions were investigated
      with a panel of Arabidopsis mutant and transgenic plants defective in one or more
      defense signaling pathways. pad4, eds5, NahG, npr1, jar1, ein2, sid2, eds1, and
      wild-type Columbia-0 and Wassilewskija-2 plants were infected with two different
      viruses, cucumber mosaic virus and oilseed rape mosaic virus. Gene expression was
      assayed by a high-throughput fiber-optic bead array consisting of 388 genes and
      by RNA gel blots. These analyses demonstrated that, in compatible host-virus
      interactions, the expression of the majority of defense-related genes is induced
      by a salicylic acid-dependent, NPR1-independent signaling pathway with a few
      notable exceptions that did require NPR1. Interestingly, none of the mutant or
      transgenic plants showed enhanced susceptibility to either cucumber mosaic virus
      or oilseed rape mosaic virus based on both symptoms and virus accumulation. This
      observation is in contrast to the enhanced disease susceptibility phenotypes that
      these mutations or transgenes confer to some bacterial and fungal pathogens.
      These experimental results suggest that expression of many defense-related genes
      in compatible host plants might share components of signaling pathways involved
      in incompatible host-pathogen interactions, but their increased expression has no
      negative effect on viral infection.

PMID- 15728342
TI  - Effects of feeding Spodoptera littoralis on lima bean leaves. II. Continuous
      mechanical wounding resembling insect feeding is sufficient to elicit herbivory
      related volatile emission.
AB  - Herbivore feeding elicits defense responses in infested plants, including the
      emission of volatile organic compounds that can serve as indirect defense
      signals. Until now, the contribution of plant tissue wounding during the feeding
      process in the elicitation of defense responses has not been clear. For example,
      in lima bean (Phaseolus lunatus), the composition of the volatiles induced by
      both the insect caterpillar Spodoptera littoralis and the snail Cepaea hortensis
      is very similar. Thus, a mechanical caterpillar, MecWorm, has been designed and
      used in this study, which very closely resembles the herbivore-caused tissue
      damage in terms of similar physical appearance and long-lasting wounding period
      on defined leaf areas. This mode of treatment was sufficient to induce the
      emission of a volatile organic compound blend qualitatively similar to that as
      known from real herbivore feeding, although there were significant quantitative
      differences for a number of compounds. Moreover, both the duration and the area
      that has been mechanically damaged contribute to the induction of the whole
      volatile response. Based on those two parameters, time and area, which can
      replace each other to some extent, a damage level can be defined. That damage
      level exhibits a close linear relationship with the accumulation of fatty acid
      derived volatiles and monoterpenes, while other terpenoid volatiles and methyl
      salicylate respond in a nonlinear manner. The results strongly suggest that the
      impact of mechanical wounding on the induction of defense responses during
      herbivore feeding was until now underestimated. Controlled and reproducible
      mechanical damage that strongly resembles the insect's feeding process represents
      a valuable tool for analyzing the role of the various signals involved in the
      induction of plant defense reactions against herbivory.

PMID- 15728341
TI  - Ozone-induced programmed cell death in the Arabidopsis radical-induced cell
      death1 mutant.
AB  - Short, high-concentration peaks of the atmospheric pollutant ozone (O(3)) cause
      the formation of cell death lesions on the leaves of sensitive plants. Numerous
      similarities between the plant responses to O(3) and pathogens suggest that O(3)
      triggers hypersensitive response-like programmed cell death (PCD). We examined
      O(3) and superoxide-induced cell death in the O(3)-sensitive radical-induced cell
      death1 (rcd1) mutant. Dying cells in O(3)-exposed rcd1 exhibited several of the
      typical morphological characteristics of the hypersensitive response and PCD.
      Double-mutant analyses indicated a requirement for salicylic acid and the
      function of the cyclic nucleotide-gated ion channel AtCNGC2 in cell death.
      Furthermore, a requirement for ATPases, kinases, transcription, Ca(2+) flux,
      caspase-like proteolytic activity, and also one or more phenylmethylsulfonyl
      fluoride-sensitive protease activities was shown for the development of cell
      death lesions in rcd1. Furthermore, mitogen-activated protein kinases showed
      differential activation patterns in rcd1 and Columbia. Taken together, these
      results directly demonstrate the induction of PCD by O(3).

PMID- 15728343
TI  - Ethylene-induced differential growth of petioles in Arabidopsis. Analyzing
      natural variation, response kinetics, and regulation.
AB  - Plants can reorient their organs in response to changes in environmental
      conditions. In some species, ethylene can induce resource-directed growth by
      stimulating a more vertical orientation of the petioles (hyponasty) and enhanced
      elongation. In this study on Arabidopsis (Arabidopsis thaliana), we show
      significant natural variation in ethylene-induced petiole elongation and
      hyponastic growth. This hyponastic growth was rapidly induced and also reversible
      because the petioles returned to normal after ethylene withdrawal. To unravel the
      mechanisms behind the natural variation, two contrasting accessions in ethylene
      induced hyponasty were studied in detail. Columbia-0 showed a strong hyponastic
      response to ethylene, whereas this response was almost absent in Landsberg erecta
      (Ler). To test whether Ler is capable of showing hyponastic growth at all,
      several signals were applied. From all the signals applied, only spectrally
      neutral shade (20 micromol m(-2) s(-1)) could induce a strong hyponastic response
      in Ler. Therefore, Ler has the capacity for hyponastic growth. Furthermore, the
      lack of ethylene-induced hyponastic growth in Ler is not the result of already
      saturating ethylene production rates or insensitivity to ethylene, as an ethylene
      responsive gene was up-regulated upon ethylene treatment in the petioles.
      Therefore, we conclude that Ler is missing an essential component between the
      primary ethylene signal transduction chain and a downstream part of the
      hyponastic growth signal transduction pathway.

PMID- 15728344
TI  - Monoterpene metabolism. Cloning, expression, and characterization of menthone
      reductases from peppermint.
AB  - (-)-Menthone is the predominant monoterpene produced in the essential oil of
      maturing peppermint (Mentha x piperita) leaves during the filling of epidermal
      oil glands. This early biosynthetic process is followed by a second, later oil
      maturation program (approximately coincident with flower initiation) in which the
      C3-carbonyl of menthone is reduced to yield (-)-(3R)-menthol and (+)-(3S)
      neomenthol by two distinct NADPH-dependent ketoreductases. An activity-based in
      situ screen, by expression in Escherichia coli of 23 putative redox enzymes from
      an immature peppermint oil gland expressed sequence tag library, was used to
      isolate a cDNA encoding the latter menthone:(+)-(3S)-neomenthol reductase.
      Reverse transcription-PCR amplification and RACE were used to acquire the former
      menthone:(-)-(3R)-menthol reductase directly from mRNA isolated from the oil
      gland secretory cells of mature leaves. The deduced amino acid sequences of these
      two reductases share 73% identity, provide no apparent subcellular targeting
      information, and predict inclusion in the short-chain dehydrogenase/reductase
      family of enzymes. The menthone:(+)-(3S)-neomenthol reductase cDNA encodes a
      35,722-D protein, and the recombinant enzyme yields 94% (+)-(3S)-neomenthol and
      6% (-)-(3R)-menthol from (-)-menthone as substrate, and 86% (+)-(3S)-isomenthol
      and 14% (+)-(3R)-neoisomenthol from (+)-isomenthone as substrate, has a pH
      optimum of 9.3, and K(m) values of 674 mum, > 1 mm, and 10 mum for menthone,
      isomenthone, and NADPH, respectively, with a k(cat) of 0.06 s(-1). The
      recombinant menthone:(-)-(3R)-menthol reductase has a deduced size of 34,070 D
      and converts (-)-menthone to 95% (-)-(3R)-menthol and 5% (+)-(3S)-neomenthol, and
      (+)-isomenthone to 87% (+)-(3R)-neoisomenthol and 13% (+)-(3S)-isomenthol,
      displays optimum activity at neutral pH, and has K(m) values of 3.0 mum, 41 mum,
      and 0.12 mum for menthone, isomenthone, and NADPH, respectively, with a k(cat) of
      0.6 s(-1). The respective activities of these menthone reductases account for all
      of the menthol isomers found in the essential oil of peppermint. Biotechnological
      exploitation of these genes could lead to improved production yields of (-)
      menthol, the principal and characteristic flavor component of peppermint.

PMID- 15728345
TI  - Water deficits affect caffeate O-methyltransferase, lignification, and related
      enzymes in maize leaves. A proteomic investigation.
AB  - Drought is a major abiotic stress affecting all levels of plant organization and,
      in particular, leaf elongation. Several experiments were designed to study the
      effect of water deficits on maize (Zea mays) leaves at the protein level by
      taking into account the reduction of leaf elongation. Proteomic analyses of
      growing maize leaves allowed us to show that two isoforms of caffeic acid/5
      hydroxyferulic 3-O-methyltransferase (COMT) accumulated mostly at 10 to 20 cm
      from the leaf point of insertion and that drought resulted in a shift of this
      region of maximal accumulation toward basal regions. We showed that this shift
      was due to the combined effect of reductions in growth and in total amounts of
      COMT. Several other enzymes involved in lignin and/or flavonoid synthesis
      (caffeoyl-CoA 3-O-methyltransferase, phenylalanine ammonia lyase,
      methylenetetrahydrofolate reductase, and several isoforms of S-adenosyl-l
      methionine synthase and methionine synthase) were highly correlated with COMT,
      reinforcing the hypothesis that the zone of maximal accumulation corresponds to a
      zone of lignification. According to the accumulation profiles of the enzymes,
      lignification increases in leaves of control plants when their growth decreases
      before reaching their final size. Lignin levels analyzed by thioacidolysis
      confirmed that lignin is synthesized in the region where we observed the maximal
      accumulation of these enzymes. Consistent with the levels of these enzymes, we
      found that the lignin level was lower in leaves of plants subjected to water
      deficit than in those of well-watered plants.

PMID- 15728346
TI  - The independence of language and mathematical reasoning.

PMID- 15728347
TI  - Assembly of the bacteriophage T4 primosome: single-molecule and ensemble studies.
AB  - Within replisomes for DNA replication, the primosome is responsible for unwinding
      double-stranded DNA and synthesizing RNA primers. Assembly of the bacteriophage
      T4 primosome on individual molecules of ssDNA or forked DNA (fDNA) has been
      studied by using FRET microscopy. On either DNA substrate, an ordered process of
      assembly begins with tight 1:1 binding of ssDNA-binding protein (gp32) and
      helicase-loading protein (gp59) to the DNA. Magnesium adenosine 5'-O-(3
      thiotriphosphate) (MgATPgammaS) mediates the weak binding of helicase (gp41) to
      DNA coated with gp32 and gp59, whereas MgATP induces gp32 and gp59 to dissociate,
      leaving gp41 bound to the DNA. Finally, primase (gp61) binds to the gp41.DNA
      complex. Ensemble studies were used to determine protein stoichiometries and
      binding constants. These single-molecule studies provide an unambiguous
      description of the pathway for assembly of the primosome on the lagging strand of
      DNA at a replication fork.

PMID- 15728348
TI  - Uric acid protects against secondary damage after spinal cord injury.
AB  - Peroxynitrite contributes to the pathogenesis of various neurodegenerative
      disorders through multiple mechanisms and is thought to mediate secondary
      neuronal cell death after spinal cord injury (SCI). Here we establish that
      physiologically relevant levels of uric acid (UA), a selective inhibitor of
      certain peroxynitrite-mediated reactions, block the toxic effects of
      peroxynitrite on primary spinal cord neurons in vitro. Furthermore,
      administration of UA at the onset of SCI in a mouse model inhibits several
      pathological changes in the spinal cord including general tissue damage,
      nitrotyrosine formation, lipid peroxidation, activation of poly(ADP-ribose)
      polymerase, and neutrophil invasion. More importantly, UA treatment improves
      functional recovery from the injury. Taken together, our findings support the
      concept that peroxynitrite contributes to the pathophysiology of secondary damage
      after SCI. They also raise the possibility that elevating UA levels may provide a
      therapeutic approach for the treatment of SCI as well as other neurological
      diseases with a peroxynitrite-mediated pathological component.

PMID- 15728349
TI  - Intramembrane aspartic acid in SCAP protein governs cholesterol-induced
      conformational change.
AB  - The polytopic membrane protein SCAP transports sterol regulatory element-binding
      proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi, thereby
      activating cholesterol synthesis. Cholesterol accumulation in the ER membranes
      changes SCAP to an alternate conformation in which it binds ER retention proteins
      called Insigs, thereby terminating cholesterol synthesis. Here, we show that the
      conserved Asp-428 in the sixth transmembrane helix of SCAP is essential for
      SCAP's dissociation from Insigs. In transfected hamster cells, mutant SCAP in
      which Asp-428 is replaced by alanine (D428A) remained in an Insig-binding
      conformation when cells were depleted of sterols. As a result, mutant SCAP failed
      to dissociate from Insigs, and it failed to carry SREBPs to the Golgi. These data
      identify an important functional residue in SCAP, and they provide genetic
      evidence that the conformation of SCAP dictates the rate of cholesterol synthesis
      in animal cells.

PMID- 15728350
TI  - An atomic resolution view of ICAM recognition in a complex between the binding
      domains of ICAM-3 and integrin alphaLbeta2.
AB  - Within the Ig superfamily (IgSF), intercellular adhesion molecules (ICAMs) form a
      subfamily that binds the leukocyte integrin alphaLbeta2. We report a 1.65-A
      resolution crystal structure of the ICAM-3 N-terminal domain (D1) in complex with
      the inserted domain, the ligand-binding domain of alphaLbeta2. This high
      resolution structure and comparisons among ICAM subfamily members establish that
      the binding of ICAM-3 D1 onto the inserted domain represents a common docking
      mode for ICAM subfamily members. The markedly different off-rates of ICAM-1, -2,
      and -3 appear to be determined by the hydrophobicity of residues that surround a
      metal coordination bond in the alphaLbeta2-binding interfaces. Variation in
      composition of glycans on the periphery of the interfaces influences on-rate.

PMID- 15728351
TI  - Fast, long-range, reversible conformational fluctuations in nucleosomes revealed
      by single-pair fluorescence resonance energy transfer.
AB  - The nucleosome core particle, the basic repeated structure in chromatin fibers,
      consists of an octamer of eight core histone molecules, organized as dimers
      (H2A/H2B) and tetramers [(H3/H4)2] around which DNA wraps tightly in almost two
      left-handed turns. The nucleosome has to undergo certain conformational changes
      to allow processes that need access to the DNA template to occur. By single-pair
      fluorescence resonance energy transfer, we demonstrate fast, long-range,
      reversible conformational fluctuations in nucleosomes between two states: fully
      folded (closed), with the DNA wrapped around the histone core, or open, with the
      DNA significantly unraveled from the histone octamer. The brief excursions into
      an extended open state may create windows of opportunity for protein factors
      involved in DNA transactions to bind to or translocate along the DNA.

PMID- 15728352
TI  - Hard superconducting nitrides.
AB  - Detailed study of the equation of state, elasticity, and hardness of selected
      superconducting transition-metal nitrides reveals interesting correlations among
      their physical properties. Both the bulk modulus and Vickers hardness are found
      to decrease with increasing zero-pressure volume in NbN, HfN, and ZrN. The
      computed elastic constants from first principles satisfy c11 > c12 > c44 for NbN,
      but c11 > c44 > c12 for HfN and ZrN, which are in good agreement with the neutron
      scattering data. The cubic delta-NbN superconducting phase possesses a bulk
      modulus of 348 GPa, comparable to that of cubic boron nitride, and a Vickers
      hardness of 20 GPa, which is close to sapphire. Theoretical calculations for NbN
      show that all elastic moduli increase monotonically with increasing pressure.
      These results suggest technological applications of such materials in extreme
      environments.

PMID- 15728353
TI  - Demonstration of toxicity to fish and to mammalian cells by Pfiesteria species:
      comparison of assay methods and strains.
AB  - Toxicity and its detection in the dinoflagellate fish predators Pfiesteria
      piscicida and Pfiesteria shumwayae depend on the strain and the use of reliable
      assays. Two assays, standardized fish bioassays (SFBs) with juvenile fish and
      fish microassays (FMAs) with larval fish, were compared for their utility to
      detect toxic Pfiesteria. The comparison included strains with confirmed toxicity,
      negative controls (noninducible Pfiesteria strains and a related nontoxic
      cryptoperidiniopsoid dinoflagellate), and P. shumwayae strain CCMP2089, which
      previously had been reported as nontoxic. SFBs, standardized by using toxic
      Pfiesteria (coupled with tests confirming Pfiesteria toxin) and conditions
      conducive to toxicity expression, reliably detected actively toxic Pfiesteria,
      but FMAs did not. Pfiesteria toxin was found in fish- and algae-fed clonal
      Pfiesteria cultures, including CCMP2089, but not in controls. In contrast,
      noninducible Pfiesteria and cryptoperidiniopsoids caused no juvenile fish
      mortality in SFBs even at high densities, and low larval fish mortality by
      physical attack in FMAs. Filtrate from toxic strains of Pfiesteria spp. in
      bacteria-free media was cytotoxic. Toxicity was enhanced by bacteria and other
      prey, especially live fish. Purified Pfiesteria toxin extract adversely affected
      mammalian cells as well as fish, and it caused fish death at environmentally
      relevant cell densities. These data show the importance of testing multiple
      strains when assessing the potential for toxicity at the genus or species level,
      using appropriate culturing techniques and assays.

PMID- 15728354
TI  - Enforced Bcl-2 expression overrides serum and feeder cell requirements for mouse
      embryonic stem cell self-renewal.
AB  - Leukemia inhibitory factor (LIF) is required, but not sufficient, for pluripotent
      mouse embryonic stem (ES) cell expansion in vitro in the absence of serum or a
      feeder cell layer, suggesting that additional signals are provided by serum or
      feeders that are necessary to support self-renewal. Here we show that transgenic
      ES cell lines expressing Bcl-2, an antiapoptotic protein, continue to self-renew
      in serum- and feeder-free conditions when supplemented with LIF; even in the
      absence of bone morphogenic proteins. Bcl-2-expressing clones sustain the
      characteristics of undifferentiated, pluripotent ES cells during long-term
      culture, and maintain their potential to differentiate into mature cell types.
      These results suggest that LIF and Bcl-2 overexpression are sufficient to expand
      these mouse pluripotent stem cells in vitro.

PMID- 15728355
TI  - Lasting impressions: motifs in protein-protein maps may provide footprints of
      evolutionary events.

PMID- 15728356
TI  - Biography of Cornelia I. Bargmann.

PMID- 15728357
TI  - Genomic characterization of non-O1, non-O139 Vibrio cholerae reveals genes for a
      type III secretion system.
AB  - Non-O1, non-O139 Vibrio cholerae can cause gastroenteritis and extraintestinal
      infections, but, unlike O1 and O139 strains of V. cholerae, little is known about
      the virulence gene content of non-O1, non-O139 strains and their phylogenetic
      relationship to other pathogenic V. cholerae. Comparative genomic microarray
      analysis of four pathogenic non-O1, non-O139 strains indicates that these strains
      are quite divergent from O1 and O139 strains. Genomic sequence analysis of a non
      O1, non-O139 strain (AM-19226) that appeared particularly pathogenic in
      experimental animals suggests that this strain carries a type III secretion
      system (TTSS) that is related to the TTSS2 gene cluster found in a pandemic clone
      of Vibrio parahaemolyticus. The genes for this V. cholerae TTSS system appear to
      be present in many clinical and environmental non-O1, non-O139 strains, including
      at least one clone that is globally distributed. We hypothesize that the TTSS
      present in some pathogenic strains of non-O1, non-O139 V. cholerae may be
      involved in the virulence and environmental fitness of these strains.

PMID- 15728358
TI  - Crystal structure of DNA sequence specificity subunit of a type I restriction
      modification enzyme and its functional implications.
AB  - Type I restriction-modification enzymes are differentiated from type II and type
      III enzymes by their recognition of two specific dsDNA sequences separated by a
      given spacer and cleaving DNA randomly away from the recognition sites. They are
      oligomeric proteins formed by three subunits: a specificity subunit, a
      methylation subunit, and a restriction subunit. We solved the crystal structure
      of a specificity subunit from Methanococcus jannaschii at 2.4-A resolution. Two
      highly conserved regions (CRs) in the middle and at the C terminus form a coiled
      coil of long antiparallel alpha-helices. Two target recognition domains form
      globular structures with almost identical topologies and two separate DNA binding
      clefts with a modeled DNA helix axis positioned across the CR helices. The
      structure suggests that the coiled-coil CRs act as a molecular ruler for the
      separation between two recognized DNA sequences. Furthermore, the relative
      orientation of the two DNA binding clefts suggests kinking of bound dsDNA and
      exposing of target adenines from the recognized DNA sequences.

PMID- 15728359
TI  - Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5).
AB  - Spinophilin is a protein that binds to protein phosphatase-1 and actin and
      modulates excitatory synaptic transmission and dendritic spine morphology. We
      have identified three sites phosphorylated by ERK2 (Ser-15 and Ser-205) and
      cyclin-dependent PK 5 (Cdk5) (Ser-17), within the actin-binding domain of
      spinophilin. Cdk5 and ERK2 both phosphorylated spinophilin in intact cells.
      However, in vitro, phosphorylation by ERK2, but not by Cdk5, was able to modulate
      the ability of spinophilin to bind to and bundle actin filaments. In neurons and
      HEK293 cells expressing GFP-tagged variants of spinophilin, imaging studies
      demonstrated that introduction of a phospho-site mimic (Ser-15 to glutamate) was
      associated with increased filopodial density. These results support a role for
      spinophilin phosphorylation by ERK2 in the regulation of spine morphogenesis.

PMID- 15728360
TI  - Platelet-derived growth factor C induces liver fibrosis, steatosis, and
      hepatocellular carcinoma.
AB  - Members of the platelet-derived growth factor (PDGF) ligand family are known to
      play important roles in wound healing and fibrotic disease. We show that both
      transient and stable expression of PDGF-C results in the development of liver
      fibrosis consisting of the deposition of collagen in a pericellular and
      perivenular pattern that resembles human alcoholic and nonalcoholic fatty liver
      disease. Fibrosis in PDGF-C transgenic mice, as demonstrated by staining and
      hydroxyproline content, is preceded by activation and proliferation of hepatic
      stellate cells, as shown by collagen, alpha-smooth muscle actin and glial
      fibrillary acidic protein staining and between 8 and 12 months of age is followed
      by the development of liver adenomas and hepatocellular carcinomas. The hepatic
      expression of a number of known profibrotic genes, including type beta1 TGF, PDGF
      receptors alpha and beta, and tissue inhibitors of matrix metalloproteinases-1
      and -2, increased by 4 weeks of age. Increased PDGF receptor alpha and beta
      protein levels were associated with activation of extracellular regulated kinase
      1 and -2 and protein kinase B. At 9 months of age, PDGF-C transgenic mice had
      enlarged livers associated with increased fibrosis, steatosis, cell dysplasia,
      and hepatocellular carcinomas. These studies indicate that hepatic expression of
      PDGF-C induces a number of profibrotic pathways, suggesting that this growth
      factor may act as an initiator of fibrosis. Moreover, PDGF-C transgenic mice
      represent a unique model for the study of hepatic fibrosis progressing to
      tumorigenesis.

PMID- 15728361
TI  - Regulation of osteoblastogenesis and bone mass by Wnt10b.
AB  - Wnts comprise a family of secreted signaling proteins that regulate diverse
      developmental processes. Activation of Wnt signaling by Wnt10b inhibits
      differentiation of preadipocytes and blocks adipose tissue development; however,
      the effect of Wnt10b on other mesenchymal lineages has not been defined. To
      explore the physiological role of Wnt signaling in bone development, we analyzed
      FABP4-Wnt10b mice, which express the Wnt10b transgene in marrow. Femurs from
      FABP4-Wnt10b mice have almost four times as much bone in the distal metaphyses
      and are mechanically stronger. These mice maintain elevated bone mass at least
      through 23 months of age. In addition, FABP4-Wnt10b mice are protected from the
      bone loss characteristic of estrogen deficiency. We used pharmacological and
      genetic approaches to demonstrate that canonical Wnt signaling stimulates
      osteoblastogenesis and inhibits adipogenesis of bipotential mesenchymal
      precursors. Wnt10b shifts cell fate toward the osteoblast lineage by induction of
      the osteoblastogenic transcription factors Runx2, Dlx5, and osterix and
      suppression of the adipogenic transcription factors C/EBPalpha and PPARgamma. One
      mechanism whereby Wnt10b promotes osteoblastogenesis is suppression of PPARgamma
      expression. Finally, Wnt10b-/- mice have decreased trabecular bone and serum
      osteocalcin, confirming that Wnt10b is an endogenous regulator of bone formation.

PMID- 15728362
TI  - Association of tissue-specific differentially methylated regions (TDMs) with
      differential gene expression.
AB  - Early studies proposed that DNA methylation could have a role in regulating gene
      expression during development [Riggs, A.D. (1975) Cytogenet. Cell Genet. 14, 9
      25]. However, some studies of DNA methylation in known tissue-specific genes
      during development do not support a major role for DNA methylation. In the
      results presented here, tissue-specific differentially methylated regions (TDMs)
      were first identified, and then expression of genes associated with these regions
      correlated with methylation status. Restriction landmark genomic scanning (RLGS)
      was used in conjunction with virtual RLGS to identify 150 TDMs [Matsuyama, T.,
      Kimura, M.T., Koike, K., Abe, T., Nakao, T., Asami, T., Ebisuzaki, T., Held,
      W.A., Yoshida, S. & Nagase, H. (2003) Nucleic Acids Res. 31, 4490-4496]. Analysis
      of 14 TDMs by methylation-specific PCR and by bisulfite genomic sequencing
      confirms that the regions identified by RLGS are differentially methylated in a
      tissue-specific manner. The results indicate that 5% or more of the CpG islands
      are TDMs, disputing the general notion that all CpG islands are unmethylated.
      Some of the TDMs are within 5' promoter CpG islands of genes, which exhibit a
      tissue-specific expression pattern that is consistent with methylation status and
      a role in tissue differentiation.

PMID- 15728363
TI  - The eukaryotic P loop NTPase Nbp35: an essential component of the cytosolic and
      nuclear iron-sulfur protein assembly machinery.
AB  - Soluble P loop NTPases represent a large protein family and are involved in
      diverse cellular functions. Here, we functionally characterized the first member
      of the Mrp/Nbp35 subbranch of this family, the essential Nbp35p of Saccharomyces
      cerevisiae. The protein resides in the cytosol and nucleus and carries an Fe/S
      cluster at its N terminus. Assembly of the Fe/S cluster requires the
      mitochondrial Fe/S cluster (ISC)-assembly and -export machineries. Depletion of
      Nbp35p strongly impairs the activity of the cytosolic Fe/S protein,
      isopropylmalate isomerase (Leu1p), whereas mitochondrial Fe/S enzymes are
      unaffected. Moreover, defects in the de novo maturation of various cytosolic and
      nuclear Fe/S proteins were observed in the absence of Nbp35p, demonstrating the
      functional involvement of Nbp35p in the biogenesis of extramitochondrial Fe/S
      proteins. Furthermore, Nbp35p genetically interacts with the closely similar P
      loop NTPase, Cfd1p, and the hydrogenase-like Nar1p, both of which were recently
      shown to perform a crucial function in cytosolic and nuclear Fe/S protein
      biogenesis. Hence, our study suggests that eukaryotic Nbp35 NTPases function in
      Fe/S protein maturation. The findings provide strong evidence for the existence
      of a highly conserved and essential machinery dedicated to assembling cytosolic
      and nuclear Fe/S proteins.

PMID- 15728364
TI  - Genome trimming: a unique strategy for replication control employed by Borna
      disease virus.
AB  - Genome and antigenome synthesis of negative-strand RNA viruses is initiated at
      promoters located in inverted terminal repeats (ITR). The ITR of Borna disease
      virus (BDV), a persisting neurotropic virus with a nuclear replication phase, are
      exceptional in that they appear to be noncomplete. Our analysis showed that the
      vast majority of genomic and antigenomic RNA molecules of BDV lack four 5'
      terminal nucleotides required for perfect complementarity with the 3' ITR. By
      using a previously undescribed reverse genetics system, we investigated whether
      the structure of the ITR would affect virus propagation. BDV rescued from cDNA
      encoding complete ITR (rBDVc) showed wild-type virulence, whereas virus rescued
      from cDNA encoding a viral genome with noncomplete ITR (rBDVnc) was strongly
      attenuated. Both recombinant viruses expressed similar RNA and protein levels in
      persistently infected cells. However, rBDVnc particles were less infectious,
      indicating that complete ITR are required for high viral replicase but not
      transcriptase activity. Interestingly, genomic RNA from purified rBDVc particles
      lacked 5'-terminal nucleotides like authentic BDV, strongly suggesting programmed
      genome truncation. By specifically trimming its genome at the 5' terminus, BDV
      seems to limit viral genome amplification, which may favor noncytolytic viral
      persistence.

PMID- 15728365
TI  - Mechanical feedback as a possible regulator of tissue growth.
AB  - Regulation of cell growth and proliferation has a fundamental role in animal and
      plant development and in the progression of cancer. In the context of
      development, it is important to understand the mechanisms that coordinate growth
      and patterning of tissues. Imaginal discs, which are larval precursors of fly
      limbs and organs, have provided much of what we currently know about these
      processes. Here, we consider the mechanism that is responsible for the observed
      uniformity of growth in wing imaginal discs, which persists in the presence of
      gradients in growth inducing morphogens in spite of the stochastic nature of cell
      division. The phenomenon of "cell competition," which manifests in apoptosis of
      slower-growing cells in the vicinity of faster growing tissue, suggests that
      uniform growth is not a default state but a result of active regulation. How can
      a patch of tissue compare its growth rate with that of its surroundings? A
      possible way is furnished by mechanical interactions. To demonstrate this
      mechanism, we formulate a mathematical model of nonuniform growth in a layer of
      tissue and examine its mechanical implications. We show that a clone growing
      faster or slower than the surrounding tissue is subject to mechanical stress, and
      we propose that dependence of the rate of cell division on local stress could
      provide an "integral-feedback" mechanism stabilizing uniform growth. The proposed
      mechanism of growth control is not specific to imaginal disc growth and could be
      of general relevance. Several experimental tests of the proposed mechanism are
      suggested.

PMID- 15728366
TI  - Rhodopsin C terminus, the site of mutations causing retinal disease, regulates
      trafficking by binding to ADP-ribosylation factor 4 (ARF4).
AB  - The maintenance of photoreceptor cell polarity is compromised by the rhodopsin
      mutations causing the human disease autosomal dominant retinitis pigmentosa. The
      severe form mutations occur in the C-terminal sorting signal of rhodopsin, VXPX
      COOH. Here, we report that this sorting motif binds specifically to the small
      GTPase ARF4, a member of the ARF family of membrane budding and protein sorting
      regulators. The effects of blocking ARF4 action were functionally equivalent to
      the effects of blocking the rhodopsin C-terminal sorting signal. ARF4 was
      essential for the generation of post-Golgi carriers targeted to the rod outer
      segments of retinal photoreceptors. Thus, the severe retinitis pigmentosa alleles
      that affect the rhodopsin sorting signal interfere with interactions between ARF4
      and rhodopsin, leading to aberrant trafficking and initiation of retinal
      degeneration.

PMID- 15728367
TI  - Antagonist of growth hormone-releasing hormone induces apoptosis in LNCaP human
      prostate cancer cells through a Ca2+-dependent pathway.
AB  - Antagonists of growth hormone-releasing hormone (GHRH) exert antiproliferative
      effects directly on cancer cells, which are mediated by the tumoral GHRH
      receptors. However, the signal transduction pathways involved in
      antiproliferative effect of GHRH antagonists have not yet been elucidated. We
      used flow cytometry to investigate whether GHRH antagonist JV-1-38 can induce
      changes in the cytosolic free Ca2+ concentration leading to apoptosis in LNCaP
      human prostate cancer cells. JV-1-38 evoked prompt Ca2+ signal in a dose
      dependent way (1-10 microM) and induced early stage of apoptosis in LNCaP human
      prostate cancer cells at a concentration effective in suppression of cell
      proliferation (10 microM) peaking after 3 h. Unexpectedly, agonist GHRH(1-29)NH2,
      which elevates cytosolic free Ca2+ concentration in pituitary somatotrophs at
      nanomolar concentrations, failed to induce Ca2+ signal or apoptosis even at a 10
      fold higher concentration (100 microM). However, agonist GHRH(1-29)NH2 inhibited
      JV-1-38-induced Ca2+ signals in a dose-dependent way without affecting the
      antagonist-induced apoptosis. Peptides unrelated to GHRH did not induce Ca2+
      signals in LNCaP human prostate cancer cells. EDTA (10 mM) or nifedipine (10
      microM) significantly reduced the Ca2+ signal and early stage of apoptosis
      induced by JV-1-38, supporting the view that the increase in intracellular Ca2+
      in response to JV-1-38 occurs primarily through extracellular Ca2+ entry through
      voltage-operated Ca2+ channels. In conclusion, GHRH antagonists activate tumoral
      GHRH receptors and are able to induce apoptosis in LNCaP human prostate cancer
      cells through a Ca2+-dependent pathway. Treatment with GHRH antagonists may offer
      a new approach to the therapy of prostate and other hormone-sensitive cancers.

PMID- 15728368
TI  - Microcomputed tomography colonography for polyp detection in an in vivo mouse
      tumor model.
AB  - This study was initiated to evaluate the efficacy of negative contrast-enhanced
      microcomputed tomography (microCT) colonography for the noninvasive detection of
      colonic tumors in living mice. After colonic preparation, 20 anesthetized
      congenic mice were scanned with high-resolution microCT. Images were displayed by
      using commercial visualization software and interpreted by two gastrointestinal
      radiologists, who were unaware of tumor prevalence and findings at gross
      pathology. Two-dimensional multiplanar images were assessed by using a five-point
      scale to distinguish colonic tumors (polyps) from fecal pellets (5 = definitely a
      tumor, 4 = probably a tumor, 3 = indeterminate, 2 = probably not a tumor, 1 =
      definitely not a tumor). Gross pathologic evaluation of excised mouse colons
      served as the reference standard. Data analysis included dichotomizing results,
      with 1-2 indicating no tumor and 3-5 indicating tumor and also receiver operator
      characteristic curve analysis with area under the curve for threshold-independent
      assessment. A total of 41 colonic polyps in 18 of the 20 mice were identified at
      gross examination on necropsy, of which 30 measured 2-5 mm and 11 measured <2 mm
      in size. The pooled per-polyp sensitivity for lesions >2 mm was 93.3% (56/60).
      The pooled per-mouse sensitivity for polyps >2 mm was 97.1% (33/34). Pooled
      specificity for distinguishing fecal pellets from tumor was 98.5% (65/66). The
      combined area under the curve from receiver operator characteristic curve
      analysis was 0.810 +/- 0.038 (95% confidence interval, 0.730-0.890). These
      findings indicate that accurate noninvasive longitudinal monitoring of colon
      tumor progression or response to various therapies is now technically feasible in
      live mice by using this microCT colonography method.

PMID- 15728369
TI  - Single-neuron responses and neuronal decisions in a vernier task.
AB  - Vernier acuity is a measure of the smallest horizontal offset between two
      vertical lines that can be behaviorally discriminated. To examine the link
      between the neuronal responses in a retinotopic mosaic and vernier acuity, we
      recorded the responses of single cells in cat lateral geniculate nucleus to a
      vertical bar stimulus that was stepped in small increments through the receptive
      fields of cells. Based on the single-trial responses evoked by stimuli at
      different positions, we calculated the spatial resolution that could be achieved.
      If the stimulus could fall anywhere in their receptive fields, single neurons had
      spatial resolutions two times worse than previously reported vernier thresholds.
      Given the known coverage factor in a cat retina, we developed a two-stage
      decision model to examine how the responses of neurons in a retinotopic mosaic
      could be processed to achieve vernier acuity. In order for psychophysical
      thresholds to be accounted for by the responses of a single cell, the stimulus
      must fall in the quarter of the receptive field that provides the most
      information about stimulus position. Alternatively, both the absolute
      psychophysical threshold for vernier acuity and its dependence on stimulus length
      can be realized by pooling the responses of a few neurons, all located on one
      side of the bar stimulus.

PMID- 15728370
TI  - Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of
      the human C3 transient receptor potential channel.
AB  - AK032317 is the GenBank accession no. of a full-length RIKEN mouse cDNA. It
      encodes a putative variant of the C3-type TRPC (transient receptor potential
      channel) that differs from the previously cloned murine TRPC3 cDNA in that it has
      a 5' extension stemming from inclusion of an additional exon (exon 0). The
      extended cDNA adds 62 aa to the sequence of the murine TRPC3. Here, we report the
      cloning of a cDNA encoding the human homologue of this extended TRPC3 having a
      highly homologous 73-aa N-terminal extension, referred to as hTRPC3a. A query of
      the GenBank genomic database predicts the existence of a similar gene product
      also in rats. Transient expression of the longer TRPC3a in human embryonic kidney
      (HEK) cells showed that it mediates Ca2+ entry in response to stimulation of the
      Gq-phospholipase C beta pathway, which is similar to that mediated by the shorter
      hTRPC3. However, after isolation of HEK cells expressing hTRPC3 in stable form,
      TRPC3a gave rise to Ca2+-entry channels that are not only activated by the Gq
      phospholipase C beta pathway (receptor-activated Ca entry) but also by
      thapsigargin triggered store depletion. In conjunction with findings from our and
      other laboratories that TRPC1, TRPC2, TRPC4, TRPC5, and TRPC7, can each mediate
      store-depletion-activated Ca2+ entry in mammalian cells, our findings with hTRC3a
      support our previous proposal that TRPCs form capacitative Ca-entry channels.

PMID- 15728371
TI  - Immunogenicity in humans of an edible vaccine for hepatitis B.
AB  - A double-blind placebo-controlled clinical trial evaluated the immunogenicity of
      hepatitis B surface antigen (HBsAg) expressed in potatoes and delivered orally to
      previously vaccinated individuals. The potatoes accumulated HBsAg at
      approximately 8.5 microg/g of potato tuber, and doses of 100 g of tuber were
      administered by ingestion. The correlate of protection for hepatitis B virus, a
      nonenteric pathogen, is blood serum antibody titers against HBsAg. After
      volunteers ate uncooked potatoes, serum anti-HBsAg titers increased in 10 of 16
      volunteers (62.5%) who ate three doses of potatoes; in 9 of 17 volunteers (52.9%)
      who ate two doses of transgenic potatoes; and in none of the volunteers who ate
      nontransgenic potatoes. These results were achieved without the coadministration
      of a mucosal adjuvant or the need for buffering stomach pH. We conclude that a
      plant-derived orally delivered vaccine for prevention of hepatitis B virus should
      be considered as a viable component of a global immunization program.

PMID- 15728372
TI  - Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen
      transgenic mouse mammary carcinoma model.
AB  - Mullerian inhibiting substance (MIS) inhibits breast cancer cell growth in vitro.
      To extend the use of MIS to treat breast cancer, it is essential to test the
      responsiveness of mammary tumor growth to MIS in vivo. Mammary tumors arising in
      the C3(1) T antigen mouse model expressed the MIS type II receptor, and MIS in
      vitro inhibited the growth of cells derived from tumors. Administration of MIS to
      mice was associated with a lower number of palpable mammary tumors compared with
      vehicle-treated mice (P=0.048), and the mean mammary tumor weight in the MIS
      treated group was significantly lower compared with the control group (P=0.029).
      Analysis of proliferating cell nuclear antigen (PCNA) expression and caspase-3
      cleavage in tumors revealed that exposure to MIS was associated with decreased
      proliferation and increased apoptosis, respectively, and was not caused by a
      decline in T antigen expression. The effect of MIS on tumor growth was also
      evaluated on xenografted human breast cancer cell line MDA-MB-468, which is
      estrogen receptor- and retinoblastoma-negative and expresses mutant p53, and thus
      complements the C3(1)Tag mouse mammary tumors that do not express estrogen
      receptor and have functional inactivation of retinoblastoma and p53. In agreement
      with results observed in the transgenic mice, MIS decreased the rate of MDA-MB
      468 tumor growth and the gain in mean tumor volume in severe combined
      immunodeficient mice compared with vehicle-treated controls (P=0.004). These
      results suggest that MIS can suppress the growth of mammary tumors in vivo.

PMID- 15728373
TI  - Juvenile hormone, reproduction, and worker behavior in the neotropical social
      wasp Polistes canadensis.
AB  - Previous studies of the division of labor in colonies of eusocial Hymenoptera
      (wasps and bees) have led to two hypotheses regarding the evolution of juvenile
      hormone (JH) involvement. The novel- or single-function hypothesis proposes that
      the role of JH has changed from an exclusively reproductive function in
      primitively eusocial species (those lacking morphologically distinct queen and
      worker castes), to an exclusively behavioral function in highly eusocial
      societies (those containing morphologically distinct castes). In contrast, the
      split-function hypothesis proposes that JH originally functioned in the
      regulation of both reproduction and behavior in ancestral solitary species. Then,
      when reproductive and brood-care tasks came to be divided between queens and
      workers, the effects of JH were divided as well, with JH involved in regulation
      of reproductive maturation of egg-laying queens, and behavioral maturation,
      manifested as age-correlated changes in worker tasks, of workers. We report
      experiments designed to test these hypotheses. After documenting age-correlated
      changes in worker behavior (age polyethism) in the neotropical primitively
      eusocial wasp Polistes canadensis, we demonstrate that experimental application
      of the JH analog methoprene accelerates the onset of guarding behavior, an age
      correlated task, and increases the number of foraging females; and we demonstrate
      that JH titers correlate with both ovarian development of queens and task
      differentiation in workers, as predicted by the split-function hypothesis. These
      findings support a view of social insect evolution that sees the contrasting
      worker and queen phenotypes as derived via decoupling of reproductive and brood
      care components of the ancestral solitary reproductive physiology.

PMID- 15728374
TI  - Inferring network mechanisms: the Drosophila melanogaster protein interaction
      network.
AB  - Naturally occurring networks exhibit quantitative features revealing underlying
      growth mechanisms. Numerous network mechanisms have recently been proposed to
      reproduce specific properties such as degree distributions or clustering
      coefficients. We present a method for inferring the mechanism most accurately
      capturing a given network topology, exploiting discriminative tools from machine
      learning. The Drosophila melanogaster protein network is confidently and robustly
      (to noise and training data subsampling) classified as a duplication-mutation
      complementation network over preferential attachment, small-world, and a
      duplication-mutation mechanism without complementation. Systematic
      classification, rather than statistical study of specific properties, provides a
      discriminative approach to understand the design of complex networks.

PMID- 15728375
TI  - Identification of a nitrogenase FeMo cofactor precursor on NifEN complex.
AB  - The biosynthesis of the FeMo cofactor (FeMoco) of Azotobacter vinelandii
      nitrogenase presumably starts with the production of its Fe/S core by NifB (the
      nifB gene product). This core is subsequently processed on the alpha2beta2
      tetrameric NifEN complex (formed by the nifE and nifN gene products). In this
      article, we identify a NifEN-bound FeMoco precursor form that can be converted to
      fully assembled FeMoco in a so-called FeMoco-maturation assay containing only
      purified components. We also establish that only molybdate, homocitrate, MgATP,
      and Fe protein are essential for FeMoco maturation. The FeMoco-maturation assay
      described here will further address the remaining questions related to the
      assembly mechanism of the ever-intriguing FeMoco.

PMID- 15728376
TI  - Barrier-to-autointegration factor is required to segregate and enclose
      chromosomes within the nuclear envelope and assemble the nuclear lamina.
AB  - Barrier-to-autointegration factor (BAF) binds dsDNA, LEM-domain proteins, and
      lamins. Caenorhabditis elegans BAF requires Ce-lamin and two LEM-domain proteins
      (Ce-emerin and Ce-MAN1) to localize during nuclear assembly. It was unknown
      whether Ce-lamin and LEM proteins, in turn, depend on Ce-BAF (mutually dependent
      structural roles). RNA interference-mediated down-regulation of Ce-BAF caused
      gross defects in chromosome segregation, chromatin decondensation, and mitotic
      progression as early as the two-cell stage, and embryos died at the approximately
      100-cell stage. Nuclear pores reassembled, whereas Ce-lamin, Ce-emerin, and Ce
      MAN1 bound chromatin but remained patchy and disorganized. The nuclear membranes
      formed but failed to enclose anaphase-bridged chromatin. Time-lapse imaging
      showed two phenotypes: anaphase-bridged chromatin that eventually resolved, and
      segregated chromatin that returned to the midzone. Thus, the assembly of BAF,
      lamins, and LEM-domain proteins is mutually dependent, and is required to capture
      segregated chromosomes within the nascent nuclear envelope. Embryos that escaped
      lethality by down-regulation of Ce-BAF grew into sterile adults with misplaced
      distal tip cells and gonads, further suggesting that mild postembryonic
      reductions in BAF disrupt tissue-specific functions.

PMID- 15728377
TI  - Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell
      migration.
AB  - To explore the mechanisms by which NO elicits endothelial cell (EC) migration we
      used murine and bovine aortic ECs in an in vitro wound-healing model. We found
      that exogenous or endogenous NO stimulated EC migration. Moreover, migration was
      significantly delayed in ECs derived from endothelial NO synthase-deficient mice
      compared with WT murine aortic EC. To assess the contribution of matrix
      metalloproteinase (MMP)-13 to NO-mediated EC migration, we used RNA interference
      to silence MMP-13 expression in ECs. Migration was delayed in cells in which MMP
      13 was silenced. In untreated cells MMP-13 was localized to caveolae, forming a
      complex with caveolin-1. Stimulation with NO disrupted this complex and
      significantly increased extracellular MMP-13 abundance, leading to collagen
      breakdown. Our findings show that MMP-13 is an important effector of NO-activated
      endothelial migration.

PMID- 15728378
TI  - Circulating transcriptome reveals markers of atherosclerosis.
AB  - Circulating monocytes mediate inflammation in atherosclerosis and may serve as
      easily accessible reporters of disease. To search for markers of atherosclerosis,
      we compared the in vivo transcriptomes of monocytes purified from patients
      undergoing carotid endarterectomy and normal subjects by using the serial
      analysis of gene expression technique. We selected a subset of differentially
      expressed monocyte-specific genes and confirmed their expression levels. The
      Finkel-Biskis-Jinkins osteosarcoma (FOS) gene was significantly increased in
      patients, and the highest levels of FOS associated with patients who had
      previously undergone coronary revascularization. The correlation between coronary
      revascularization and FOS was higher than that compared with the cardiac risk
      marker high sensitivity C-reactive protein. In vitro inhibition of FOS using
      small interfering RNA and 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor
      simvastatin (statin) affected monocyte activation and suggested an important role
      in pathogenesis. Given the prominent role of FOS in inflammation and
      calcification, its association with atherosclerosis severity has clear
      pathophysiologic bases as well as clinical implications as a marker. Our results
      suggest that analysis of gene expression in circulating cells may provide
      biological and clinical insights into human atherosclerosis, and that this type
      of approach may be applicable for studying other types of diseases.

PMID- 15728379
TI  - Amphetamine induces dopamine efflux through a dopamine transporter channel.
AB  - Drugs of abuse, including cocaine, amphetamine (AMPH), and heroin, elevate
      extracellular dopamine (DA) levels in the brain, thereby altering the
      activity/plasticity of reward circuits and precipitating addiction. The
      physiological release of DA occurs through the calcium-dependent fusion of a
      synaptic vesicle with the plasma membrane. Extracellular DA is cleared by uptake
      through the Na+/Cl- -dependent DA transporter (DAT). In contrast, the substrate
      AMPH induces nonvesicular release of DA mediated by DAT. Extracellular AMPH is
      generally believed to trigger DA efflux through DAT by facilitating exchange for
      cytosolic DA. Here, in outside-out patches from heterologous cells stably
      expressing DAT or from dopaminergic neurons, by using ionic conditions in the
      patch pipette that mimic those produced by AMPH stimulation, we report that AMPH
      causes DAT-mediated DA efflux by two independent mechanisms: (i) a slow process
      consistent with an exchange mechanism and (ii) a process that results in rapid
      (millisecond) bursts of DA efflux through a channel-like mode of DAT. Because
      channel-like release of DA induced by AMPH is rapid and contains a large number
      of DA molecules, with a single burst of DA on par with a quantum of DA from
      exocytotic release of a vesicle, this burst mode of release may play a role in
      the synaptic actions and psychostimulant properties of AMPH and related
      compounds. Unlike AMPH, the endogenous substrate DA, when present on both sides
      of the plasma membrane, inhibits this channel-like activity, thereby suggesting
      that the DAT channel-like mode cannot accumulate DA against a concentration
      gradient.

PMID- 15728380
TI  - Dissection of synaptic excitability phenotypes by using a dominant-negative
      Shaker K+ channel subunit.
AB  - During nervous system development, synapses undergo morphological change as a
      function of electrical activity. In Drosophila, enhanced activity results in the
      expansion of larval neuromuscular junctions. We have examined whether these
      structural changes involve the pre- or postsynaptic partner by selectively
      enhancing electrical excitability with a Shaker dominant-negative (SDN) potassium
      channel subunit. We find that the SDN enhances neurotransmitter release when
      expressed in motoneurons, postsynaptic potential broadening when expressed in
      muscles and neurons, and selectively suppresses fast-inactivating, Shaker
      mediated IA currents in muscles. SDN expression also phenocopies the canonical
      behavioral phenotypes of the Sh mutation. At the neuromuscular junction, we find
      that activity-dependent changes in arbor size occur only when SDN is expressed
      presynaptically. This finding indicates that elevated postsynaptic membrane
      excitability is by itself insufficient to enhance presynaptic arbor growth. Such
      changes must minimally involve increased neuronal excitability.

PMID- 15728381
TI  - Cross-regulation of TNF and IFN-alpha in autoimmune diseases.
AB  - Cytokines, most particularly TNF and type I IFN (IFN-alphabeta), have been long
      considered essential elements in the development of autoimmunity. Identification
      of TNF in the pathogenesis of rheumatoid arthritis and TNF antagonist therapy
      represent successes of immunology. IFN-alphabeta plays a major role in systemic
      lupus erythematosus (SLE), a prototype autoimmune disease characterized by a
      break of tolerance to nuclear components. Here, we show that TNF regulates IFN
      alpha production in vitro at two levels. First, it inhibits the generation of
      plasmacytoid dendritic cells (pDCs), a major producer of IFN-alphabeta, from
      CD34+ hematopoietic progenitors. Second, it inhibits IFN-alpha release by
      immature pDCs exposed to influenza virus. Neutralization of endogenous TNF
      sustains IFN-alpha secretion by pDCs. These findings are clinically relevant, as
      five of five patients with systemic juvenile arthritis treated with TNF
      antagonists display overexpression of IFN-alpha-regulated genes in their blood
      leukocytes. These results, therefore, might provide a mechanistic explanation for
      the development of anti-dsDNA antibodies and lupus-like syndrome in patients
      undergoing anti-TNF therapy.

PMID- 15728382
TI  - Study of the high-potential iron sulfur protein in Halorhodospira halophila
      confirms that it is distinct from cytochrome c as electron carrier.
AB  - The role of high-potential iron sulfur protein (HiPIP) in donating electrons to
      the photosynthetic reaction center in the halophilic gamma-proteobacterium
      Halorhodospira halophila was studied by EPR and time-resolved optical
      spectroscopy. A tight complex between HiPIP and the reaction center was observed.
      The EPR spectrum of HiPIP in this complex was drastically different from that of
      the purified protein and provides an analytical tool for the detection and
      characterization of the complexed form in samples ranging from whole cells to
      partially purified protein. The bound HiPIP was identified as iso-HiPIP II. Its
      Em value at pH 7 in the form bound to the reaction center was approximately 100
      mV higher (+140 +/- 20 mV) than that of the purified protein. EPR on oriented
      samples showed HiPIP II to be bound in a well defined geometry, indicating the
      presence of specific protein-protein interactions at the docking site. At
      moderately reducing conditions, the bound HiPIP II donates electrons to the
      cytochrome subunit bound to the reaction center with a half-time of < or =11
      micros. This donation reaction was analyzed by using Marcus's outer-sphere
      electron-transfer theory and compared with those observed in other HiPIP
      containing purple bacteria. The results indicate substantial differences between
      the HiPIP- and the cytochrome c2-mediated re-reduction of the reaction center.

PMID- 15728383
TI  - Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to
      contribute to kidney tissues.
AB  - The use of stem cells has enabled the successful generation of simple organs.
      However, anatomically complicated organs such as the kidney have proven more
      refractory to stem-cell-based regenerative techniques. Given the limits of
      allogenic organ transplantation, an ultimate therapeutic solution is to establish
      self-organs from autologous stem cells and transplant them as syngrafts back into
      donor patients. To this end, we have striven to establish an in vitro organ
      factory to build up complex organ structures from autologous adult stem cells by
      using the kidney as a target organ. Cultivation of human mesenchymal stem cells
      in growing rodent embryos enables their differentiation within a spatially and
      temporally appropriate developmental milieu, facilitating the first step of
      nephrogenesis. We show that a combination of whole-embryo culture, followed by
      organ culture, encourages exogenous human mesenchymal stem cells to differentiate
      and contribute to functional complex structures of the new kidney.

PMID- 15728384
TI  - Quantitative kinetic analysis of the bacteriophage lambda genetic network.
AB  - The lysis-lysogeny decision of bacteriophage lambda has been a paradigm for a
      developmental genetic network, which is composed of interlocked positive and
      negative feedback loops. This genetic network is capable of responding to
      environmental signals and to the number of infecting phages. An interplay between
      CI and Cro functions suggested a bistable switch model for the lysis-lysogeny
      decision. Here, we present a real-time picture of the execution of lytic and
      lysogenic pathways with unprecedented temporal resolution. We monitor, in vivo,
      both the level and function of the CII and Q gene regulators. These activators
      are cotranscribed yet control opposite developmental pathways. Conditions that
      favor the lysogenic response show severe delay and down-regulation of Q activity,
      in both CII-dependent and CII-independent ways. Whereas CII activity correlates
      with its protein level, Q shows a pronounced threshold before its function is
      observed. Our quantitative analyses suggest that by regulating CII and CIII, Cro
      plays a key role in the ability of the lambda genetic network to sense the
      difference between one and more than one phage particles infecting a cell. Thus,
      our results provide an improved framework to explain the longstanding puzzle of
      the decision process.

PMID- 15728385
TI  - Synthetic analogues of migrastatin that inhibit mammary tumor metastasis in mice.
AB  - Tumor metastasis is the most common cause of death in cancer patients. Here, we
      show that two, fully synthetic migrastatin analogues, core macroketone and core
      macrolactam, are potent inhibitors of metastasis in a murine breast tumor model.
      Administration of these readily accessible compounds nearly completely inhibits
      lung metastasis of highly metastatic mammary carcinoma cells. Treatment of tumor
      cells with core macroketone and core macrolactam blocks Rac activation,
      lamellipodia formation, and cell migration, suggesting that these chemical
      compounds interfere with the invasion step of the metastatic process. These
      compounds also inhibit the migration of human metastatic breast cancer cells,
      prostate cancer cells, and colon cancer cells but not normal mammary-gland
      epithelial cells, fibroblasts, and leukocytes. These data demonstrate that the
      macroketone and macrolactam core structures are specific small-molecule
      inhibitors of tumor metastasis. These compounds or their analogues could
      potentially be used in cancer-therapy strategies.

PMID- 15728386
TI  - Barx2 functions through distinct corepressor classes to regulate hair follicle
      remodeling.
AB  - The hair-growth cycle, a complex biological system requiring coordinate
      alterations in gene expression and cellular behavior, provides a challenging
      model for investigating the interplay of specific transcriptional regulation
      events. Here we report that the Barx2 homeodomain factor serves as a regulator of
      hair follicle remodeling (catagen), and loss of Barx2 in mice causes a defect
      both in the initiation and progression of catagen, resulting in a protracted
      first catagen, and later, causing short hair in adult gene-deleted mice. Barx2
      negatively regulates its own promoter, and our study highlights the role of Barx2
      as a repressor in the skin that can, unexpectedly, functionally interact with two
      WD40-domain factors distantly related to the yeast corepressor Tup1. These two
      corepressors, transducin-like enhancer of split and transducin beta-like 1,
      function through distinct and independent interactions with Barx2 for the
      repression of gene targets, including the Barx2 gene itself, emphasizing the
      roles of complementary repression strategies in engrailed homology-1 motif
      containing homeodomain factors. Together, our data suggest that the hair
      remodeling defect of Barx2 mutant mice could be explained, in part, by failure to
      repress one or more critical target genes.

PMID- 15728387
TI  - DNA coiled coils.
AB  - We report the coiled-coil structure of DNA, which is generated by the
      dodecanucleotide d(ATATATATATAT). The structure has been determined by single
      crystal x-ray crystallography. The molecules form duplexes with single-stranded
      overhangs, which associate with neighbor molecules and give rise to infinite
      double helices in a coiled-coil conformation, with staggered nicks in both
      strands. The coiled coils have six dodecamer duplexes per turn. Despite the
      presence of nicks, the structure is very rigid. Statistical disorder is present,
      which gives rise to continuous scattering along the layer lines. This observation
      can be interpreted by the classical theory of coiled coils developed for
      proteins, which we apply here to a DNA structure. A clear splitting of the
      original layer lines of the DNA double helix is detected. The structure we have
      found adds a previously unrecognized element to the architectures that can be
      built from DNA oligonucleotides. Any duplex with complementary single-strand
      overhangs should be expected to give rise to regular coiled-coil structures.

PMID- 15728388
TI  - Evidence from renal proximal tubules that HCO3- and solute reabsorption are
      acutely regulated not by pH but by basolateral HCO3- and CO2.
AB  - Respiratory acidosis, a decrease in blood pH caused by a rise in [CO(2)], rapidly
      triggers a compensatory response in which the kidney markedly increases its
      secretion of H(+) from blood to urine. However, in this and other acid-base
      disturbances, the equilibrium CO(2) + H(2)O HCO(3)(-) + H(+) makes it impossible
      to determine whether the critical parameter is [CO(2)], [HCO(3)(-)], and/or pH.
      Here, we used out-of-equilibrium CO(2)/HCO(3)(-) solutions to alter basolateral
      (BL) [HCO(3)(-)], [CO(2)], or pH, systematically and one at a time, on isolated
      perfused S2 rabbit proximal tubules. We found that increasing [HCO(3)(-)](BL)
      from 0 to 44 mM, at a fixed [CO(2)](BL) of 5% and a fixed pH(BL) of 7.40, caused
      HCO(3)(-) reabsorption (J(HCO(3))) to fall by half but did not significantly
      affect volume reabsorption (J(V)). Increasing [CO(2)](BL) from 0% to 20%, at a
      fixed [HCO(3)(-)](BL) of 22 mM and pH(BL) of 7.40, caused J(HCO(3)) to rise 2.5
      fold but did not significantly affect J(V). Finally, increasing pH(BL) from 6.80
      to 8.00, at a fixed [HCO(3)(-)](BL) of 22 mM and [CO(2)](BL) of 5%, did not
      affect either J(HCO(3)) or J(V). Analysis of the J(HCO(3)) and J(V) data implies
      that, as the tubule alters J(HCO(3)), it compensates the reabsorption of other
      solutes to keep J(V) approximately constant. Because the cells cannot respond
      acutely to pH changes, we propose that the responses of J(HCO(3)) and the
      reabsorption of other solutes to changes in [HCO(3)(-)](BL) or [CO(2)](BL)
      involve sensors for basolateral HCO(3)(-) and CO(2).

PMID- 15728389
TI  - Expression of an additional cathelicidin antimicrobial peptide protects against
      bacterial skin infection.
AB  - Cathelicidin antimicrobial peptides are effectors of innate immune defense in
      mammals. Humans and mice have only one cathelicidin gene, whereas domesticated
      mammals such as the pig, cow, and horse have multiple cathelicidin genes. We
      hypothesized that the evolution of multiple cathelicidin genes provides these
      animals with enhanced resistance to infection. To test this, we investigated the
      effects of the addition of cathelicidins by combining synthetic cathelicidin
      peptides in vitro, by producing human keratinocytes that overexpress
      cathelicidins in culture, or by producing transgenic mice that constitutively
      overexpress cathelicidins in vivo. The porcine cathelicidin peptide PR-39 acted
      additively with human cathelicidin LL-37 to kill group A Streptococcus (GAS).
      Lentiviral delivery of PR-39 enhanced killing of GAS by human keratinocytes.
      Finally, transgenic mice expressing PR-39 under the influence of a K14 promoter
      showed increased resistance to GAS skin infection (50% smaller necrotic ulcers
      and 60% fewer surviving bacteria). Similarly constructed transgenic mice designed
      to overexpress their native cathelicidin did not show increased resistance. These
      findings demonstrate that targeted gene transfer of a xenobiotic cathelicidin
      confers resistance against infection and suggests the benefit of duplication and
      divergence in the evolution of antimicrobial peptides.

PMID- 15728390
TI  - A remarkably effective copper(II)-dipyridylphosphine catalyst system for the
      asymmetric hydrosilylation of ketones in air.
AB  - The combination of catalytic amounts of optically active dipyridylphosphine and
      CuF(2) along with hydride donor PhSiH(3) generated in situ a remarkably reactive
      catalyst system (substrate-to-ligand molar ratio up to 100,000) for the highly
      enantioselective hydrosilylation of a broad spectrum of aryl alkyl ketones (up to
      97% enantiomeric excess) in normal atmosphere and at mild conditions (ambient
      temperature to -20 degrees C, compatible with traces of moisture) in the absence
      of base additives. Furthermore, a highly effective catalytic asymmetric
      hydrosilylation of unsymmetrical diarylketones using this catalyst system was
      also realized (up to 98% enantiomeric excess). The introduction of the
      dipyridylphosphine ligands in the air-accelerated and inexpensive metal-mediated
      asymmetric hydrosilylation of ketones makes the present system highly attractive
      and thus provides an excellent opportunity for practical applications.

PMID- 15728391
TI  - Microsatellite instability regulates transcription factor binding and gene
      expression.
AB  - Microsatellites are tandemly repeated simple sequence DNA motifs widely prevalent
      in eukaryotic and prokaryotic genomes. In pathogenic bacteria, instability of
      these hypermutable loci through slipped-strand mispairing mediates the high
      frequency reversible switching of phenotype expression, i.e., phase variation.
      Phase-variable expression of NadA, an outer membrane protein and adhesin of the
      pathogen Neisseria meningitidis, is mediated by changes in the number of TAAA
      repeats located upstream of the core promoter of nadA. Here we report that loss
      or gain of TAAA repeats affects the binding of the transcriptional regulatory
      protein IHF to the nadA promoter. Thus, phase-variable transcription of nadA
      potentially incorporates interplay between stochastic (mutational) and
      prescriptive (classical) mechanisms of gene regulation.

PMID- 15728393
TI  - Synergistic proinflammatory responses induced by polymicrobial colonization of
      epithelial surfaces.
AB  - The epithelial surfaces of the upper respiratory tract are continuously exposed
      to a wide variety of commensal microorganisms. In addition to acting as a
      physical barrier, epithelial cells respond to specific microbial products with
      the generation of signals, such as cytokines, that trigger inflammation. Because
      they are common components of the nasopharyngeal flora that share the potential
      to cause disease, we investigated the effects of Haemophilus influenzae and
      Streptococcus pneumoniae, alone and in combination, on human respiratory
      epithelial cells in culture and in a murine model of nasopharyngeal colonization.
      Exposure of A549 or Detroit 562 epithelial cells to both S. pneumoniae and H.
      influenzae led to a synergistic increase in production of IL-8, the major
      neutrophil chemokine in the airway, through an NF-kappaB-dependent mechanism.
      Likewise, nasal cocolonization of mice caused a synergistic rise in local
      production of macrophage inflammatory protein 2 in nasal lavage fluid and
      subsequent recruitment of neutrophils. This synergistic effect depended on
      production of the pore-forming cytolytic toxin, pneumolysin, by S. pneumoniae and
      activation of host p38 mitogen-activated protein kinase. Although both H.
      influenzae and S. pneumoniae have ligands for Toll-like receptors (TLRs) TLR2 and
      TLR4, synergistic activation was TLR2- and TLR4-independent. Thus, epithelial
      surfaces are capable of amplifying proinflammatory responses during concurrent
      stimulation by multiple microbial species. These synergistic responses,
      demonstrated both in vitro and in vivo, may contribute to inflammation of heavily
      colonized mucosal barriers.

PMID- 15728392
TI  - Time-resolved electrometric and optical studies on cytochrome bd suggest a
      mechanism of electron-proton coupling in the di-heme active site.
AB  - Time-resolved electron transfer and electrogenic H(+) translocation have been
      compared in a bd-type quinol oxidase from Escherichia coli and its E445A mutant.
      The high-spin heme b(595) is found to be retained by the enzyme in contrast to
      the original proposal, but it is not reducible even by excess of dithionite. When
      preincubated with the reductants, both the WT (b(558)(2+), b(595)(2+), d(2+)) and
      E445A mutant oxidase (b(558)(2+), b(595)(3+), d(2+)) bind O(2) rapidly, but
      formation of the oxoferryl state in the mutant is approximately 100-fold slower
      than in the WT enzyme. At the same time, the E445A substitution does not affect
      intraprotein electron re-equilibration after the photolysis of CO bound to
      ferrous heme d in the one-electron-reduced enzyme (the so-called "electron
      backflow"). The backflow is coupled to membrane potential generation. Electron
      transfer between hemes d and b(558) is electrogenic. In contrast, electron
      transfer between hemes d and b(595) is not electrogenic, although heme b(595) is
      the major electron acceptor for heme d during the backflow, and therefore is not
      likely to be accompanied by net H(+) uptake or release. The E445A replacement
      does not alter electron distribution between hemes b(595) and d in the one
      electron reduced cytochrome bd [E(m)(d) > E(m)(b(595)), where E(m) is the
      midpoint redox potential]; however, it precludes reduction of heme b(595), given
      heme d has been reduced already by the first electron. Presumably, E445 is one of
      the two redox-linked ionizable groups required for charge compensation of the di
      heme oxygen-reducing site (b(595), d) upon its full reduction by two electrons.

PMID- 15728394
TI  - The power of phylogenetic comparison in revealing protein function.

PMID- 15728395
TI  - Growth and shape stability of a biological membrane adhesion complex in the
      diffusion-mediated regime.
AB  - We examine the process of expansion of a focal adhesion complex by which a
      biological membrane containing mobile binders adheres to a substrate with
      complementary binders. Attention is focused on the situation, common among living
      cells, in which the mean mobile binder density is insufficient to overcome
      generic resistance to close approach of the membrane to its substrate. For the
      membrane to adhere, binders must be recruited from adjacent regions to join an
      adhesion patch of density adequate for adhesion, thereby expanding the size of
      the patch. The specific configuration examined is the expansion of a circular
      adhesion zone for which diffusive binder transport driven by a chemical potential
      gradient is the mechanism of binder recruitment. An aspect of the process of
      particular interest is the stability of the circular shape of the expanding
      front. It is found that the adhesion front radius increases as radical(t), where
      t is the time elapsed since nucleation, and that the circular shape becomes
      unstable under sinusoidal perturbations for radii large compared with the
      nucleation size, as observed in recent experiments.

PMID- 15728396
TI  - Balancing the generation and elimination of reactive oxygen species.

PMID- 15728397
TI  - Co-proxamol and suicide: preventing the continuing toll of overdose deaths.
AB  - Restricting means for suicide is a key element in suicide prevention strategies
      of all countries where these have been introduced. Preventing deaths from
      analgesic overdoses is highlighted in the National Suicide Prevention Strategy
      for England. The problem of self-poisoning with the prescription-only drug co
      proxamol (dextropropoxyphene plus paracetamol) has received attention in several
      countries. We have conducted a review of the international literature related to
      possible strategies to tackle this problem. In England and Wales in 1997-1999,
      18% of drug-related suicides involved co-proxamol; these constituted 5% of all
      suicides. Death usually results from the toxic effects of dextropropoxyphene on
      respiration or cardiac function. Death from co-proxamol overdose may occur
      rapidly, the lethal dose can be relatively low, and the effects are potentiated
      by alcohol and other CNS depressants. The majority of co-proxamol overdose deaths
      occur before hospital treatment can be received. The risk can extend to others in
      the household of the person for whom the drug is prescribed. While there is
      limited evidence that educational strategies have been effective in reducing
      deaths from co-proxamol poisoning, initiatives in Scandinavia, Australia and the
      UK to restrict availability of co-proxamol have produced promising results. Given
      the paucity of evidence for superior therapeutic efficacy of co-proxamol over
      other less toxic analgesics, there are good reasons to question whether it should
      continue to be prescribed.

PMID- 15728398
TI  - Therapeutic modulation of allergic airways disease with leukotriene receptor
      antagonists.
AB  - Although asthma is one of the most common chronic respiratory conditions, it
      often remains unrecognized and undertreated, while patients are often reluctant
      to comply with regular inhaled anti-inflammatory and bronchodilator therapy.
      Allergic rhinitis co-exists with asthma in as many as 40% of patients, and can be
      regarded as a continuum of the same inflammatory disease process. Corticosteroids
      are the 'gold standard' first-line treatment for both conditions, and have a
      significant impact upon underlying inflammation, symptoms and long-term outcome.
      Cysteinyl leukotrienes are potent airway inflammatory mediators, suggesting that
      treatment antagonizing their effects could play a role in disease management. In
      recent years, leukotriene receptor antagonists have provided a further
      therapeutic option in the management of allergic airways disease. These drugs are
      orally active, can be administered once daily, and provide a systemic approach to
      the management of patients with asthma and allergic rhinitis. We review the
      pharmacology of leukotriene receptor antagonists, their potential role in
      clinical practice in patients with allergic airways disease, and likely areas for
      further research.

PMID- 15728399
TI  - Regional differences in the provision of adult renal dialysis services in the UK.
AB  - BACKGROUND: Provision of renal dialysis varies between UK regions. AIM: To
      analyse these differences in provision and investigate their causes. DESIGN:
      Questionnaire-based survey. METHODS: A questionnaire was posted to all renal
      provider units and renal commissioning groups in the UK. Questions covered issues
      such as dialysis modalities and patient choice. Data were collected by telephone
      interview (or post in some cases) and analysed using SPSS. RESULTS: All renal
      provider units in the UK responded. A full range of modalities was provided by
      the majority of units. Clear variations in the level and quality of dialysis
      provision were seen between the UK regions. These included variation in choice of
      dialysis modality, provision of high-cost drugs, vascular access waiting times,
      number of support staff and availability of spare dialysis slots. DISCUSSION: The
      considerable variation between UK regions in the provision of adult renal
      dialysis services cannot be entirely explained by age or ethnic variation, and is
      in part due to limited bed space, dialysis machines and support staff, as well as
      changes in commissioning arrangements. To meet the requirements of the renal
      national service framework in most regions, changes to policy and funding will be
      required, such that the relatively new commissioning groups implement more
      appropriate funding structures in closer dialogue with their provider units.

PMID- 15728400
TI  - A simple score for estimating the long-term risk of fracture in patients using
      oral glucocorticoids.
AB  - BACKGROUND: Previous analyses of risk factors for glucocorticoid (GC)-induced
      osteoporosis have focused on the estimation of relative rather than absolute
      fracture probability. AIM: To estimate risk scores for the individual probability
      of fracture in GC users. DESIGN: Retrospective data analysis. METHODS: We
      evaluated all patients aged 40 years or older with a prescription for oral GCs in
      the General Practice Research Database (GPRD), which comprises the computerized
      medical records of around 7 million UK subjects. Individual risk factors for
      osteoporotic fractures were identified, and combined in a predictive model for 10
      year absolute fracture risk. RESULTS: Of 191 752 oral GC users aged > or =40
      years, 7412 experienced an osteoporotic fracture. Several characteristics
      independently contributed to the fracture risk score (GC therapy, age, gender,
      fall history, fracture history, body mass index, smoking, previous diagnoses, use
      of medication, recent hospitalization and indication for GC treatment). Scores of
      30, 40 and 50 corresponded to absolute 5-year fracture risks of 6.2%, 15.3% and
      35.2%, respectively. A woman aged 65 years with RA, low BMI, and a previous
      history of fracture and falls, who used 15 mg GC daily (total risk score 54)
      would have a 5-year fracture risk of 47% (a man with similar history, 30.1%).
      Short-term use of high-dose GC therapy (> or =30 mg) was associated with only a
      small increased risk of osteoporotic fracture (RR 1.21, 95%CI 1.04-1.42) in
      patients with a history of GC use. DISCUSSION: This risk score helps to predict
      an individual's risk of fracture during GC use. Decisions about bone protection
      treatment could be based on long-term risks of fracture.

PMID- 15728401
TI  - Angiotensin-converting-enzyme inhibitors slow renal decline in IgA nephropathy,
      independent of tubulointerstitial fibrosis at presentation.
AB  - BACKGROUND: Tubulointerstitial fibrosis (TIF) is a marker of progression of
      diabetic and non-diabetic nephropathy, correlating with creatinine clearance
      (CCr), and functional outcome. Angiotensin-converting-enzyme inhibitors (ACEIs)
      slow the rate of decline of renal function in proteinuric patients. AIM: To
      examine whether ACEIs affect TIF, directly or indirectly. DESIGN: Prospective 3
      year follow-up study. METHODS: We enrolled 49 patients with IgA nephropathy
      (IgAN), treating some with ACE inhibitors (n = 26, 1-2 mg/day temocapril or
      trandolapril) and some with calcium-channel blockers (CCB, n = 23, 2.5-5 mg/day
      amlodipine). Blood pressure, serum creatinine, and urinalysis were measured
      monthly, and 24-h endogenous creatinine clearance (CCr) at least once a year.
      RESULTS: In the CCB group, TIF was positively correlated with the rate of decline
      in CCr (dCCr), consistent with previous observations. In the ACEI group, dCCr was
      lower (0.02 +/- 0.02 vs. 0.06 +/- 0.03), and the TIF-dCCr correlation was absent.
      DISCUSSION: In the absence of post-treatment histological data, it is not
      possible to say whether ACEIs have an effect on TIF. However, ACEIs appear to
      slow the progression of renal failure in IgAN, regardless of the degree of TIF at
      presentation.

PMID- 15728402
TI  - Kaposi's sarcoma in kidney transplant recipients: a 23-year experience.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is a relatively common malignancy after kidney
      transplantation, accounting for up to 80% of all malignancies in developing
      countries. AIM: To assess the frequency of KS in renal transplant recipients, and
      determine the impact of demographic factors, immunosuppression and treatment
      options. DESIGN: Retrospective study in a single centre in South Africa. METHODS:
      Charts and pathology reports of 542 recipients of 623 kidney allografts treated
      at our institution between 1976 and 1999 were reviewed. RESULTS: After a mean
      follow-up of 6.4 years, 21 (3.9%) recipients had KS, representing 47.7% of all
      post-transplant malignancies. KS accounted for more post-transplant cancers in
      non-White than White patients (79.1% vs. 11.7%, p < 0.001). KS was equally common
      in males and females, and was not more frequent under cyclosporine. Skin
      involvement was universal; visceral disease occurred in six patients (28.6%).
      Sixteen (94.1%) patients with limited skin disease and two (100%) with
      superficial nodal disease responded to withdrawal or reduction of
      immunosuppression. Renal function was preserved when immunosuppression was
      reduced instead of withdrawn (p = 0.02). Patients with vital organ involvement
      succumbed rapidly to KS. Post-mortem examination revealed more extensive disease
      than was suspected clinically. DISCUSSION: Ethnic differences exist in the
      frequency of KS in patients residing in the same geographical area. Since
      withdrawal results in graft loss, reducing immunosuppression should be first-line
      treatment for patients with disease limited to skin, and possibly for disease of
      the superficial lymph nodes. The malignant behaviour of KS, and extent of
      pathological involvement, cast doubt on the idea that KS is a hyperplasia rather
      than a true malignancy.

PMID- 15728403
TI  - Parkinson's disease: the first common neurological disease due to auto
      intoxication?
AB  - Parkinson's disease may be a disease of autointoxication. N-methylated pyridines
      (e.g. MPP+) are well-established dopaminergic toxins, and the xenobiotic enzyme
      nicotinamide N-methyltransferase (NNMT) can convert pyridines such as 4
      phenylpyridine into MPP+, using S-adenosyl methionine (SAM) as the methyl donor.
      NNMT has recently been shown to be present in the human brain, a necessity for
      neurotoxicity, because charged compounds cannot cross the blood-brain barrier.
      Moreover, it is present in increased concentration in parkinsonian brain. This
      increase may be part genetic predisposition, and part induction, by excessive
      exposure to its substrates (particularly nicotinamide) or stress. Elevated
      enzymic activity would increase MPP+-like compounds such as N-methyl nicotinamide
      at the same time as decreasing intraneuronal nicotinamide, a neuroprotectant at
      several levels, creating multiple hits, because Complex 1 would be poisoned and
      be starved of its major substrate NADH. Developing xenobiotic enzyme inhibitors
      of NNMT for individuals, or dietary modification for the whole population, could
      be an important change in thinking on primary and secondary prevention.

PMID- 15728404
TI  - Why do older patients die in a heatwave?

PMID- 15728405
TI  - Near-fatal pulmonary air embolus from iatrogenic injection of air during contrast
      administration.

PMID- 15728406
TI  - Norethisterone-induced cholestasis.

PMID- 15728407
TI  - Isolated microscopic haematuria.

PMID- 15728408
TI  - Evaluating acid-base disorders.

PMID- 15728409
TI  - The obesity epidemic.

PMID- 15728410
TI  - Let's talk about sex.

PMID- 15728411
TI  - Severe necrotic scrotal ulcers: a relapse note in Behcet's disease.

PMID- 15728412
TI  - Flares of systemic disease in primary Sjogren's syndrome.

PMID- 15728413
TI  - Eosinophilic fasciitis and eosinophilic colitis: a rare association.

PMID- 15728415
TI  - Low grip strength is associated with bone mineral density and vertebral fracture
      in women.
AB  - OBJECTIVES: Grip strength has been reported to be associated with bone mass
      locally at the forearm and also at distant skeletal sites, including the spine
      and hip. Less is known about the association between low grip strength and risk
      of vertebral fracture. The aim of this study was to examine the association
      between low grip strength, bone mineral density at the hip and spine, and
      vertebral fracture in middle-aged and elderly European men and women. METHODS:
      Men and women aged 50 yr and over were recruited for participation in a screening
      survey of vertebral osteoporosis across Europe. Subjects who agreed to take part
      had an interviewer-administered questionnaire and lateral spinal radiographs
      performed. Subjects were assessed also for grip strength using a handgrip
      dynamometer (range 0-300 mmHg). A subsample of those recruited had bone mineral
      density measurements performed at the spine and femoral neck. Subjects had repeat
      lateral spine radiographs performed a mean of 3.8 yr following the baseline
      survey. Linear regression analysis was used to determine the association between
      low grip strength and bone mineral density at the hip and spine. Logistic
      regression was used to determine the association between grip strength and both
      prevalent and incident vertebral fracture. RESULTS: One thousand two hundred and
      sixty-five men and 1380 women with data concerning grip strength and bone mineral
      density were included in the analysis. In women, after age adjustment, compared
      with those with 'normal' grip, those with 'impaired' (231-299 mmHg) and low grip
      (<231 mmHg) had significantly lower bone mass at the spine and femoral neck. In
      men, those with low grip strength had a lower BMD at the spine and hip than those
      in the normal group. However, because of the small numbers with submaximal grip
      strength, the confidence intervals around all estimates included zero. Adjustment
      for body size and levels of physical activity had little effect on the results.
      In addition, among women, after adjustment for age, body mass index and physical
      activity levels, compared with those with normal grip, those with low grip
      strength had an increased risk of developing incident vertebral fracture (odds
      ratio = 2.67; 95% confidence interval 1.13, 6.30). Further adjustment for spine
      bone density had little influence on the association (odds ratio = 2.60).
      CONCLUSIONS: In women, low grip strength is associated with low bone mineral
      density at both the spine and hip and an increased risk of incident vertebral
      fracture. These associations cannot be explained by differences in body size or
      lifestyle.

PMID- 15728416
TI  - A novel device for the measurement of proprioception in the hand.
AB  - BACKGROUND: Together with visual information, awareness of limb position and
      movement is essential for limb coordination. A proprioceptive deficit has been
      demonstrated in a number of rheumatological disorders. There is a lack of a
      portable device for measuring hand proprioception in the field. METHODS: A
      compact portable device for measuring joint position sense in the
      metacarpophalangeal joint of the index finger of either hand was constructed.
      This device was manually operated and required the subject to match the position
      of the hidden finger with a surface-mounted silhouette. Reliability studies were
      performed over three consecutive days in 12 normal volunteers. RESULTS:
      Intrasubject variability [95% confidence interval (CI)] was 0.86 degrees (0.04
      1.76) between days 1 and 2, and 1.23 degrees (1.04-3.50) between days 2 and 3.
      The intraclass correlation coefficient (95% CI) between all 3 days was 0.92 (0.85
      0.96). Average proprioceptive error (95% CI) in the sample population was 5.72
      degrees (1.23-10.2) over the 3 days. This value was 5.94 degrees , 5.79 degrees
      and 5.42 degrees on days 1, 2 and 3, respectively. No difference was found
      between sexes but dominant hands gave smaller errors (mean dominant error 5.11
      degrees , mean non-dominant error 6.35 degrees ; t = -3.4, P = 0.002).
      CONCLUSIONS: This report describes a new portable device for measuring
      proprioception in the hand. Reproducibility was shown to be good on an individual
      and group basis. These results are promising and warrant larger age- and sex
      related studies. The ease and portability of the device make it ideal for use in
      epidemiological studies of rheumatological disorders involving the hands,
      including joint hypermobility.

PMID- 15728417
TI  - Damage of cutaneous peripheral nervous system evolves differently according to
      the disease phase and subset of systemic sclerosis.
AB  - OBJECTIVE: Evidence shows that peripheral nervous system (PNS) is involved in
      systemic sclerosis (SSc), but few morphological studies have assessed the
      ultrastructural pathological modifications. The aim was to study ultrastructural
      modifications of skin PNS fibres in SSc according to subsets [limited SSc (lSSc)
      and diffuse SSc (dSSc)] and phases (early and advanced) of the disease. METHODS:
      Skin biopsies were taken from the forearms of 23 SSc patients (11 lSSc and 12
      dSSc) and 10 controls. Each biopsy was processed for transmission electron
      microscopy (TEM). RESULTS: At TEM, observation in skin from early lSSc, signs of
      inflammation were evident, while PNS fibres were not damaged. The microvascular
      wall showed hypertrophic endothelial cells bulging into the lumen. In advanced
      lSSc, fibrosis prevailed on inflammation and slight ultrastructural alterations
      of PNS fibres were evident in the papillary derma. In early dSSc, ultrastructural
      alterations of PNS fibres, similar to those observed in the advanced phase of
      lSSc, were found together with signs of inflammation and fibrosis. In advanced
      dSSc, in the papillary and reticular dermis PNS fibres were reduced and showed
      relevant ultrastructural alterations. CONCLUSIONS: In SSc, PNS ultrastructure
      damage is linked to the progression and severity of skin involvement. The
      alterations evolve from the early to the advanced phase mainly in the diffuse
      subset. In particular, the severe PNS lesions found in advanced lSSc are already
      present and widely diffuse in early dSSc and the microvascular involvement in
      early lSSc seems to precede the modification of the PNS in the skin. Thus, an
      early therapeutic approach can be useful to reduce the progression of PNS and
      skin damage in SSc patients.

PMID- 15728418
TI  - Joint hypermobility syndrome in childhood. A not so benign multisystem disorder?
AB  - OBJECTIVES: Joint hypermobility (JH) or "ligamentous laxity" is felt to be an
      underlying risk factor for many types of musculoskeletal presentation in
      paediatrics, and joint hypermobility syndrome (JHS) describes such disorders
      where symptoms become chronic, often more generalized and associated with
      functional impairment. Clinical features are felt to have much in common with
      more severe disorders, including Ehlers-Danlos syndrome (EDS), osteogenesis
      imperfecta and Marfan syndrome, although this has not been formally studied in
      children. We defined the clinical characteristics of all patients with joint
      hypermobility-related presentations seen from 1999 to 2002 in a tertiary referral
      paediatric rheumatology unit. METHODS: Patients were identified and recruited
      from paediatric rheumatology clinic and ward, and a dedicated paediatric
      rheumatology hypermobility clinic at Great Ormond Street Hospital. Data were
      collected retrospectively on the patients from the paediatric rheumatology
      clinics (1999-2002) and prospectively on patients seen in the hypermobility
      clinic (2000-2002). Specifically, historical details of developmental milestones,
      musculoskeletal or soft tissue diagnoses and symptoms, and significant past
      medical history were recorded. Examination features sought included measurements
      of joint and soft tissue laxity, and associated conditions such as scoliosis,
      dysmorphic features, cardiac murmurs and eye problems. RESULTS: One hundred and
      twenty-five children (64 females) were included on whom sufficient clinical data
      could be identified and who had clinical problems ascribed to JH present for
      longer than 3 months. Sixty-four were from the paediatric rheumatology clinic and
      61 from the hypermobility clinic. No differences were found in any of the
      measures between the two populations and results are presented in a combined
      fashion. Three-quarters of referrals came from paediatricians and general
      practitioners but in only 10% was hypermobility recognized as a possible cause of
      joint complaint. The average age at onset of symptoms was 6.2 yr and age at
      diagnosis 9.0 yr, indicating a 2- to 3-yr delay in diagnosis. The major
      presenting complaint was arthralgia in 74%, abnormal gait in 10%, apparent joint
      deformity in 10% and back pain in 6%. Mean age at first walking was 15.0 months;
      48% were considered "clumsy" and 36% as having poor coordination in early
      childhood. Twelve per cent had "clicky" hips at birth and 4% actual congenital
      dislocatable hip. Urinary tract infections were present in 13 and 6% of the
      female and male cases, respectively. Thirteen and 14%, respectively, had speech
      and learning difficulties diagnosed. A history of recurrent joint sprains was
      seen in 20% and actual subluxation/dislocation of joints in 10%. Forty per cent
      had experienced problems with handwriting tasks, 48% had major limitations of
      school-based physical education activities, 67% other physical activities and 41%
      had missed significant periods of schooling because of symptoms. Forty-three per
      cent described a history of easy bruising. Examination revealed that 94% scored >
      or =4/9 on the Beighton scale for generalized hypermobility, with knees (92%),
      elbows (87%), wrists (82%), hand metacarpophalangeal joints (79%), and ankles
      (75%) being most frequently involved. CONCLUSIONS: JHS is poorly recognized in
      children with a long delay in the time to diagnosis. Although there is a referral
      bias towards joint symptoms, a surprisingly large proportion is associated with
      significant neuromuscular and motor development problems. Our patients with JHS
      also show many overlap features with genetic disorders such as EDS and Marfan
      syndrome. The delay in diagnosis results in poor control of pain and disruption
      of normal home life, schooling and physical activities. Knowledge of the
      diagnosis and simple interventions are likely to be highly effective in reducing
      the morbidity and cost to the health and social services.

PMID- 15728419
TI  - BSR guidelines on standards of care for persons with rheumatoid arthritis.

PMID- 15728420
TI  - [18F]FDG-PET of giant-cell aortitis.

PMID- 15728421
TI  - Hand use and patterns of joint involvement in osteoarthritis. A comparison of
      female dentists and teachers.
AB  - OBJECTIVES: To investigate the effect of mechanical stress on finger
      osteoarthritis (OA) by comparing women from two occupations with different hand
      load but the same socio-economic grade, and to investigate whether hand load may
      affect the pattern of joint involvement in OA. METHODS: Radiographs of both hands
      of 295 dentists and 248 teachers were examined. Each interphalangeal (distal,
      proximal and thumb interphalangeal) and the metacarpophalangeal joints were
      graded (0 = no OA, 4 = severe OA) separately by using reference images. The co
      involvement of different hand joints was analysed by logistic regression.
      RESULTS: The distal interphalangeal joints were the most frequently involved
      joints. The non-dominant hand was more frequently affected by OA of grade 2 or
      more than the dominant hand. The prevalence of OA of grade 2 or more in any
      finger joint and also in any distal interphalangeal joint was higher among the
      teachers compared with the dentists (59 vs 48%, P = 0.020 and 58 vs 47%, P <
      0.010 respectively). Finger OA showed more clustering in the ring and little
      fingers and more row clustering and symmetry in the teachers than in the dentists
      [age-adjusted odds ratio (OR) = 1.57, 95% confidence interval (CI) 1.10-2.23, OR
      = 1.84, 95% CI 1.28-2.64, and OR = 1.98, 95% CI 1.38-2.86 respectively]. The OR
      of more severe OA (grade 3 or more) in the right-hand thumb and the index and
      middle fingers was significantly elevated among the dentists compared with the
      teachers (OR 2.61, 95% CI 1.03-6.59). CONCLUSION: Our findings indicate that
      finger OA in middle-aged women is highly prevalent and often polyarticular. Hand
      use may have a protective effect on finger joint OA, whereas continuing joint
      overload may lead to joint impairment.

PMID- 15728423
TI  - Preliminary survey of outdoor gamma dose rates in Lesvos Island (Greece).
AB  - This study reports the first attempt to record the radioactive background due to
      gamma radiation in Lesvos Island (Greece). The study reports the results from 335
      outdoor total gamma effective dose rate measurements conducted using GPS
      navigation and a Geiger-Muller detector (Bicron, Micro Sievert) on the whole
      surface of the island together with a digital map produced by appropriate mapping
      GIS programme. The study also reports the measurements of outdoor gamma dose
      rates due to the 238U, 232Th and 40K radionuclides as estimated via in situ gamma
      ray spectrometry measurements performed at 26 sites using a 3 x 3 inch NaI
      (thallium activated) portable detector. The results from the outdoor total gamma
      effective dose rates range between 0.0023 and 0.28 microSv h(-1). The highest
      outdoor total gamma effective dose rates (0.013-0.28 microSv h(-1)) were detected
      in the northeastern part of the island and the intermediate rates (0.066-0.13
      microSv h(-1)) in the central region. The outdoor gamma dose rates due to 238U,
      232Th and 40K radionuclides range between 1.7 +/- 0.8 and 154 +/- 7 nGy h(-1)
      with an average of 86 +/- 6 nGy h(-1). The average contribution of each of the
      examined radionuclides (238U, 232Th and 40K) to the total gamma dose rate was
      found to be equal to 12 +/- 4% for 238U, 58 +/- 6% for 232Th and 29 +/- 7% for
      40K, respectively.

PMID- 15728422
TI  - Moderately intensive exercise in a temperate pool for patients with rheumatoid
      arthritis: a randomized controlled study.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of moderately
      intensive pool exercise therapy on patients with rheumatoid arthritis (RA).
      METHODS: Forty-six patients with chronic RA were randomly assigned to a treatment
      group and a control group. The treatment group (n = 20) exercised in a temperate
      pool twice a week for 12 weeks. The control group (n = 23) continued with their
      previous activities. Aerobic capacity, measured by means of a submaximum bicycle
      test, and the physical component of the SF-36 were chosen as the primary outcome
      measures. Two tests of muscle endurance were chosen as the secondary outcome
      measure. Additional functional tests and instruments were included. RESULTS: No
      significant differences between the groups were found for the primary outcome
      measures. Significant improvements in the following aspects of muscular function
      (P < 0.05) were found in the treatment group when their performance was compared
      with that of the control group: isometric shoulder endurance, grip force, dynamic
      endurance of lower extremities (chair test) and muscle function of lower
      extremities. Significant improvements were also found for vitality (SF-36)
      compared with the control group. The improvements in the training group were
      maintained for 3 months. CONCLUSIONS: Pool exercise therapy of moderate intensity
      significantly improved muscle endurance in the upper and lower extremities in
      patients with RA, while no impact on aerobic capacity was found. However, the
      study population was small and there is a need for further studies with larger
      populations.

PMID- 15728424
TI  - Monte Carlo study of MOSFET dosemeter characteristics: dose dependence on photon
      energy, direction and dosemeter composition.
AB  - MOSFET dosemeters are emerging as a versatile tool in various medical physics and
      health physics dose measurements. It is an important but difficult task to
      understand their energy and directional dependences because of their unique
      features. This paper presents a study to characterise a MOSFET dosemeter using
      Monte Carlo simulation method. Monoenergetic photon beams ranging from 15 to 6
      MeV were simulated to study the energy and angular dependences. The results were
      compared with published experimental data. The Monte Carlo model also provided
      insightful information on optimising the dosemeter design by examining how
      various regions of the dosemeter contributed to the dose. Detailed energy
      deposition processes were further analysed by tracking individual particles
      inside the dosemeter.

PMID- 15728425
TI  - TRAF2: a double-edged sword?
AB  - Ubiquitination is best known for its role in targeting proteins for degradation
      by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is
      also rapidly accumulating. One example of the regulatory, rather than
      proteolytic, function of ubiquitin is provided by study of the tumor necrosis
      factor (TNF) receptor-associated factor (TRAF) proteins, which function as
      ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to
      mediate protein kinase activation through a proteasome-independent mechanism.
      Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a
      positive role in the canonical pathway that activates nuclear factor kappaB (NF
      kappaB) through IkappaB kinase beta (IKKbeta), but a negative role in the
      noncanonical pathway that activates NF-kappaB through IKKalpha. These opposing
      roles of TRAF proteins may be linked to their ability to synthesize distinct
      forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can
      mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is
      targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by
      the NF-kappaB inhibitor A20. Thus, ubiquitin chains are dynamic switches that can
      influence signaling outputs in dramatically different ways.

PMID- 15728426
TI  - The TRP superfamily of cation channels.
AB  - The transient receptor potential (TRP) protein superfamily consists of a diverse
      group of cation channels that bear structural similarities to Drosophila TRP. TRP
      channels play important roles in nonexcitable cells; however, an emerging theme
      is that many TRP-related proteins are expressed predominantly in the nervous
      system and function in sensory physiology. The TRP superfamily is divided into
      seven subfamilies, the first of which is composed of the "classical" TRPs" (TRPC
      subfamily). Some TRPCs may be store-operated channels, whereas others appear to
      be activated by production of diacylglycerol or regulated through an exocytotic
      mechanism. Many members of a second subfamily (TRPV) function in sensory
      physiology and respond to heat, changes in osmolarity, odorants, and mechanical
      stimuli. Two members of the TRPM family function in sensory perception and three
      TRPM proteins are chanzymes, which contain C-terminal enzyme domains. The fourth
      and fifth subfamilies, TRPN and TRPA, include proteins with many ankyrin repeats.
      TRPN proteins function in mechanotransduction, whereas TRPA1 is activated by
      noxious cold and is also required for the auditory response. In addition to these
      five closely related TRP subfamilies, which comprise the Group 1 TRPs, members of
      the two Group 2 TRP subfamilies, TRPP and TRPML, are distantly related to the
      group 1 TRPs. Mutations in the founding members of these latter subfamilies are
      responsible for human diseases. Each of the TRP subfamilies are represented by
      members in worms and flies, providing the potential for using genetic approaches
      to characterize the normal functions and activation mechanisms of these channels.

PMID- 15728427
TI  - Teaching resources. Growth factor and receptor tyrosine kinases.
AB  - This Teaching Resource provides lecture notes and slides for a graduate-level
      class on ligand regulation of signaling by receptor tyrosine kinases and
      receptors involved in the Wnt canonical pathway. It is part of a series of
      lectures that constitute the Cell Signaling Systems course. A description of the
      lecture, along with a set of slides used to present this information, is
      provided.

PMID- 15728428
TI  - Teaching resources. Protein kinases.
AB  - This Teaching Resource provides lecture notes and slides for a class covering the
      structure and function of protein kinases and is part of the course "Cell
      Signaling Systems: A Course for Graduate Students." The lecture begins with a
      discussion of the genomics and evolutionary relationships among kinases and then
      proceeds to describe the structure-function relationships of specific kinases,
      the molecular mechanisms underlying substrate specificity, and selected issues in
      regulation of kinase activity.

PMID- 15728429
TI  - Death by tricyclic: the real antidepressant scandal?

PMID- 15728430
TI  - NICE: The National Institute of Clinical Excellence -- or Eccentricity?
      Reflections on the Z-drugs as hypnotics.

PMID- 15728431
TI  - NICE review: not nice for patients!

PMID- 15728432
TI  - Making decisions in the absence of high quality clinical evidence: we need to
      bring some science into the judgement.

PMID- 15728433
TI  - Short-term treatment with hypnotic drugs for insomnia: going beyond the evidence.

PMID- 15728434
TI  - A NICE missed opportunity?

PMID- 15728435
TI  - Effects of peripheral sympathetic blockade with dapiprazole on the fear-inhibited
      light reflex.
AB  - Fear (e.g. associated with the threat of an electric shock) causes an increase in
      initial pupil diameter (IPD) and a decrease in the amplitude of the light reflex
      response. There is evidence for dissociation between the two responses to threat:
      only the reduction in light reflex response amplitude is sensitive to the
      anxiolytic drug diazepam. We examined the effects of peripheral sympathetic
      blockade with the alpha(1)-adrenoceptor antagonist dapiprazole on both responses
      to threat on the basis of the hypothesis that only the response of the IPD will
      be affected, whereas the response of the light reflex will remain unaffected.
      Twelve healthy volunteers (Experiment 1) and eight healthy volunteers with
      smaller pupils (Experiment 2) participated in one experimental session.
      Dapiprazole 0.5% (two drops of 20 microl, three times) was instilled in the
      subjects' right or left eye while the contralateral eye was treated with placebo
      eye drops (artificial tear, two drops of 20 microl, three times) according to a
      single-blind balanced design. Pupil diameter was monitored by infrared binocular
      television pupillometry. At the point of maximum dapiprazole-evoked miosis, the
      light reflex was elicited three times in each of three Safe blocks (no
      possibility of electric shock), alternating with three Threat blocks (possibility
      of electric shock). At the end of each Safe and Threat block, subjects rated
      their mood and feelings on the Visual Analogue Scales. In Experiment 1,
      dapiprazole caused significant miosis. Threat increased subjectively rated
      anxiety and inhibited the light reflex. The inhibition of the light reflex was
      unaffected by dapiprazole. The threat-induced increase in IPD was also unaffected
      by dapiprazole, probably due to a ceiling effect curtailing the threat-induced
      increase in IPD. In the smaller pupil group in Experiment 2, where the possible
      contribution of a ceiling effect was minimized, dapiprazole suppressed the threat
      induced increase in IPD. The inhibition of the light reflex by threat is likely
      to reflect central parasympathetic inhibition and is unlikely to involve the
      peripheral sympathetic innervation of the iris. The threat-induced increase in
      IPD is likely to reflect mainly central sympathetic excitation. The different
      central autonomic mechanisms underlying the two pupillary responses to threat may
      explain the dissociation between the separate effects of threat on IPD and light
      reflex amplitude.

PMID- 15728436
TI  - Assessment of modafinil on attentional processes in a five-choice serial reaction
      time test in the rat.
AB  - It is well known that modafinil is an effective wake-promoting agent, but there
      is growing evidence to suggest that modafinil may also enhance some aspects of
      cognition. In man, modafinil has been shown to enhance vigilance in sleep
      deprived and/or narcoleptic subjects and also to improve executive-type
      functioning (predominantly inhibitory response control processes) across a
      variety of human patient population groups. Preclinically, a delay-dependent
      improvement has been reported with modafinil in a mouse T-maze test of working
      memory. To investigate further the role of modafinil as a potential cognition
      enhancer, the effects of modafinil on attentional processes were assessed in the
      rat. The aim of the present study was to evaluate the potential of modafinil to
      enhance five-choice serial reaction time test (5-CSRT) performance. Lister Hooded
      rats received 32-128 mg/kg modafinil and 5-CSRT performance was assessed under
      standard and test parametric conditions in which the attentional load was
      increased, and also under conditions of scopolamine pre-treatment. Modafinil
      failed to significantly enhance 5-CSRT performance under standard conditions.
      Similarly, modafinil was unable to reverse the deficits in accuracy and/or
      increased omission errors induced by either parametric or pharmacological
      manipulations. Indeed, at higher doses, modafinil caused an increase in premature
      responding under certain test conditions, suggestive of increased impulsivity.
      The present findings suggest that, although modafinil may enhance vigilance in
      sleep-deprived human subjects, attentional processes in normal awake rats remain
      unaffected. No evidence was found to support a modafinil-induced improvement in
      response control; rather, under conditions of increased attentional load,
      modafinil appeared to facilitate impulsive responding. Finally, the failure of
      modafinil to improve a scopolamine-induced performance deficit suggests that
      modafinil does not act on the cholinergic system directly.

PMID- 15728437
TI  - Effects of phenytoin on memory, cognition and brain structure in post-traumatic
      stress disorder: a pilot study.
AB  - Phenytoin (Dilantin) is an anticonvulsant used in the treatment of epilepsy. It
      is believed to act by modulation of glutamatergic transmission. Because the
      neurobiology of post-traumatic stress disorder (PTSD) has been hypothesized to
      involve alterations in glutamatergic transmission with subsequention
      neurotoxicity, we assessed the effects of phenytoin on cognition and brain
      structure in PTSD patients. Phenytoin was administered in an open label fashion
      for 3 months to nine adult patients with PTSD related to a variety of traumas,
      including early abuse, combat and car accidents. Subjects underwent magnetic
      resonance imaging for measurement of whole brain and hippocampal volume, and
      neuropsychological testing of memory and cognition, before and after treatment.
      Phenytoin treatment resulted in a significant 6% increase in right brain volume
      (p < 0.05). Increased hippocampal volume was correlated with reductions in
      symptom severity as measured by the Clinician Administered PTSD Scale and
      improvements in executive function as measured by the Trails test. However,
      treatment associated improvements in memory and cognition did not achieve
      statistical significance. These findings suggest that phenytoin treatment may be
      associated with changes in brain structure in patients with PTSD.

PMID- 15728438
TI  - Evidence for a combined genetic effect of the 5-HT(1A) receptor and serotonin
      transporter genes in the clinical outcome of major depressive patients treated
      with citalopram.
AB  - In the context of a long-term follow-up study, we analysed the possible
      implication of the 5-HT(1A) receptor gene (HTR1A) -1018C/G polymorphism in the
      clinical outcome of major depressive patients treated with citalopram. We had
      previously reported an association between variation on the SERT gene (SLC6A4)
      and clinical remission after citalopram treatment. In the present 12-week follow
      up study, the combined effect of HTR1A and SLC6A4 genes in clinical outcome and
      response to citalopram was also evaluated. The sample consisted of 130 patients,
      all of Spanish origin, who were diagnosed as having a current major depressive
      episode according to DSM-IV criteria. A 21-item Hamilton Depression Rating Scale
      was used to assess severity of symptoms at the beginning and during the follow-up
      to determine the outcome and remission status at week 12. Patients were genotyped
      for HTR1A gene and, in addition, for two polymorphisms at the CYP2C19 gene, which
      together account for the 87% of the Caucasian poor metabolizer phenotype. Data
      were analysed adjusting for the effect of poor metabolizers in clinical response.
      No independent effect was found for the 5-HT(1A) receptor gene in relation to
      clinical outcome or remission after citalopram treatment. However, a combined
      genetic effect of HTR1A and SLC6A4 genes was found to influence the clinical
      outcome of patients [F(4,102) = 2.89, p= 0.02]. When considering the remission
      status, an increase of patients carrying the risk genotype combination (S/S-G/G)
      was found among those subjects who did not reach remission (Fisher's exact test =
      0.009). Our results suggest that the combined effect of the serotonin transporter
      and the 5-HT(1A) receptor genes could be related to the clinical outcome of
      depressive patients treated with citalopram.

PMID- 15728439
TI  - Limited cognitive benefits in Stage +2 postmenopausal women after 6 weeks of
      treatment with Ginkgo biloba.
AB  - Gingko biloba has cognitive benefits both in populations suffering from dementia
      and after acute treatment in healthy volunteers, with some evidence indicating
      that those with poorer cognitive performance show greater benefit. We have
      previously found that 1 week of treatment with ginkgo improved attention, memory
      and mental flexibility in post-menopausal women, but the evidence for any
      beneficial effects of longer treatment is less well-established. The present
      study aimed to determine whether cognitive benefits, similar to those previously
      found after 1 week of treatment, would persist after 6 weeks of treatment, and
      whether those with poorer cognitive performance would benefit more. In a placebo
      controlled, double-blind study, postmenopausal women (aged 51-67 years) were
      randomly allocated to receive a standardized extract of ginkgo (LI 1370, Lichtwer
      Pharma, Marlow, UK) (one capsule/day of 120 mg, n = 45) or matching placebo (n =
      42) for 6 weeks. According to an established reproductive staging system,
      subjects were divided into those in the early (Stage +1; mean age 55 years) and
      late (Stage +2: mean age 61 years) stages of menopause. At baseline and after 6
      weeks of treatment, subjects completed tests of mental flexibility, planning,
      memory and sustained attention, and ratings of mood, sleepiness, bodily and
      menopausal symptoms. The only significant effects of ginkgo were in the test of
      mental flexibility, in which there were significant menopausal stage-ginkgo
      interactions. This was because subjects in Stage +2 required fewer trials to
      complete the task and made fewer errors after ginkgo treatment, whereas those in
      Stage +1 showed no benefits. Subjects in Stage +2 had poorer performance at
      baseline compared to those in Stage +1 both in this task and the test of planning
      ability. The beneficial effects of ginkgo were limited to the test of mental
      flexibility and to those with poorer performance.

PMID- 15728440
TI  - Undiagnosed impaired fasting glucose and diabetes mellitus amongst inpatients
      receiving antipsychotic drugs.
AB  - The associations between psychosis, antipsychotic drugs and diabetes mellitus
      have not been precisely defined but it has been repeatedly suggested that
      atypical antipsychotics are more likely to give rise to diabetes than are
      conventional drugs. This belief is largely based on healthcare database analyses
      which, in part, rely on the assumption that all cases of diabetes are identified
      in practice. We examined records of 606 hospitalized patients receiving
      antipsychotic treatment and found an apparent prevalence of diabetes and impaired
      fasting glucose of 6.4%. From this sample of patients, we investigated 166
      patients (fasting blood samples) who were not known to have any disorder of
      glucose homeostasis and identified 10 cases of impaired fasting glucose and nine
      cases of diabetes mellitus (11.4% of those tested). Nine of these cases had
      documented evidence of previous testing for diabetes. Apparent prevalence of
      diabetes and impaired fasting glucose was 16.9% in those tested in practice or
      the study. Diagnosis was significantly associated with age [odds ratio (OR) 1.02]
      and treatment duration with current drug (OR 1.01). Adjusted ORs of diagnosis
      were not significantly different for any atypical antipsychotic compared with
      conventional drugs. It is concluded that there was a clinically significant
      prevalence of undiagnosed diabetes and impaired fasting glucose in those
      individuals receiving antipsychotics. Importantly, database analyses may
      underestimate the true prevalence of diabetes in similar populations and
      erroneously ascribe increased risk to certain drug treatments.

PMID- 15728442
TI  - Clozapine-induced type-2 diabetes mellitus: possible mechanisms and implications
      for clinical practice.
AB  - The atypical antipsychotic clozapine has been reported to be associated with
      metabolic adverse effects, including type-2 diabetes mellitus. We present two
      cases of diabetes mellitus associated with clozapine treatment. One case resolved
      entirely upon withdrawal of the drug, whereas the other did not. We discuss the
      molecular basis of the diabetogenic action of clozapine and recommendations for
      monitoring.

PMID- 15728441
TI  - Sudden death in a patient with Tourette syndrome during a clinical trial of
      ziprasidone.

PMID- 15728443
TI  - Risperidone and breast-feeding.
AB  - We present the case of a breast-feeding woman with acute psychotic symptoms after
      delivery, which were treated with the antipsychotic agent risperidone. Serum
      levels of risperidone and 9-hydroxyrisperidone could be detected in both the
      mother and her infant. Drug-levels in breast milk were ten-fold lower compared to
      maternal serum. The patient responded well to antipsychotic treatment. Her infant
      did not display any adverse effects and psychomotor development was normal. In
      this case, risperidone was a safe treatment option for the breast-feeding mother
      and her infant. We also provide a brief overview of the clinically relevant data
      concerning antipsychotics and breast-feeding.

PMID- 15728444
TI  - Successfully switching acetylcholinesterase inhibitor therapy in probable Lewy
      body dementia.
AB  - Lewy body disease is a common cause of dementia. Pharmacological therapies for
      the symptomatic treatment of this disorder are few and largely consist of
      acetylcholinesterase inhibitors. No guidelines exist regarding poor response or
      intolerability with such medications. This report discusses a case of an elderly
      woman with a diagnosis of probable Lewy body dementia who had significant
      improvement with donepezil but discontinued it due to side effects. She was
      switched to rivastigmine which she tolerated and which had a similar clinical
      response. The process of switching is discussed in light of the lack of specific
      guidelines.

PMID- 15728445
TI  - Monoclonal antibodies: producing magic bullets by somatic cell hybridization.

PMID- 15728446
TI  - Continuous cultures of fused cells secreting antibody of predefined specificity.
      1975.

PMID- 15728447
TI  - Variegation of the immune response with dendritic cells and pathogen recognition
      receptors.
AB  - One of the most fundamental questions in biology is: "How do cells differentiate
      in the right place, at the right time, into the right kinds?" Understanding the
      phenomenon of cell differentiation in its spatial and temporal framework is a
      prelude to understanding the development and physiology of all multicellular
      systems, including the immune system. Insights over the past 2300 years, since
      Aristotle, suggest that biological differentiation is guided by the interplay
      between genetic programs and specific environmental signals. This is exemplified
      by the mammalian immune response to pathogens, where qualitatively different
      types can emerge. Although it is appreciated that this type immunity is critical
      for optimal defense against different pathogens, the early "decision-making
      mechanisms" are largely obscure. Recent developments in innate immunity and
      genomics, especially in the biology of dendritic cells (DCs) and pathogen
      recognition receptors, have stimulated intense research in understanding the
      mechanisms guiding the differentiation of Th1, Th2, and T regulatory responses.
      In this study, I summarize recent findings which suggest that activation of DCs
      via distinct pathogen recognition receptors stimulate different gene expression
      programs and signaling networks in DCs that guide the variegation of immune
      responses.

PMID- 15728448
TI  - Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and
      function.
AB  - A major consequence of microbial infection is the tissue injury that results from
      the host inflammatory response. In acne, inflammation is due in part to the
      ability of Propionibacterium acnes to activate TLR2. Because all-trans retinoic
      acid (ATRA) decreases inflammation in acne, we investigated whether it regulates
      TLR2 expression and function. Treatment of primary human monocytes with ATRA led
      to the down-regulation of TLR2 as well as its coreceptor CD14, but not TLR1 or
      TLR4. The ability of a TLR2/1 ligand to trigger monocyte cytokine release was
      inhibited by pre- and cotreatment with ATRA; however, TLR4 activation was
      affected by cotreatment only. ATRA also down-regulated monocyte cytokine
      induction by P. acnes. These data indicate that ATRA exerts an anti-inflammatory
      effect on monocytes via two pathways, one specifically affecting TLR2/1 and CD14
      expression and one independent of TLR expression. Agents that target TLR
      expression and function represent a novel strategy to treat inflammation in
      humans.

PMID- 15728449
TI  - Cutting edge: microbial products elicit formation of dendritic cell aggresome
      like induced structures in macrophages.
AB  - In response to a maturation stimulus, dendritic cells undergo the formation of
      ubiquitinated protein aggregates known as dendritic cell aggresome-like induced
      structures (DALIS). DALIS are thought to act as Ag storage structures, allowing
      for the prioritized degradation of proteins during infection. In this study, we
      demonstrate that murine macrophages can also form ubiquitinated protein
      aggregates that are indistinguishable from DALIS. These were formed in a dose-
      and time-dependent manner, and in response to a variety of microbial products.
      Surprisingly, the proteasome did not accumulate on these ubiquitinated protein
      structures, further underlining the difference between DALIS and aggresomes. Our
      studies suggest that DALIS formation is important for the function of Ag
      presenting immune cells during infection.

PMID- 15728450
TI  - Cutting edge: priming of CTL by transcutaneous peptide immunization with
      imiquimod.
AB  - CTL are important in combating cancer and viruses. Therefore, triggering the
      complete potential of CTL effector functions by new vaccination strategies will
      not only improve prophylaxis of tumor or virus-related diseases, but also open
      opportunities for effective therapeutic immunizations. Using transcutaneous
      immunization, we show that epicutaneous (e.c.)(4) application of an ointment
      containing a CTL epitope and the TLR7 ligand imiquimod is highly effective in
      activating T cells in mice using TCR-transgenic CTL or in wild-type mice.
      Transcutaneous immunization-activated CTL mount a full-blown immune response
      against the target epitope characterized by proliferation, cytolytic activity,
      and the production of IFN-gamma that is completely restricted to the epitope used
      for vaccination. Our results obtained by simple e.c. application of an ointment,
      without further skin irritating procedures, provide the basis for the development
      of new, easy to use vaccines against cancer or virus-associated diseases.

PMID- 15728451
TI  - Cutting edge: p27Kip1 deficiency reduces the requirement for CD28-mediated
      costimulation in naive CD8+ but not CD4+ T lymphocytes.
AB  - Cell cycle re-entry of quiescent T cells is dependent upon cyclin-dependent
      kinase 2. Inhibition of cyclin-dependent kinase 2 by p27(Kip1) is believed to be
      the principal constraint on S-phase entry in T cells. We report that deficiency
      for p27(Kip1) has a more pronounced effect on the expansion of murine naive
      CD8(+) T cells and that this disparity is due to a reduced requirement for CD28
      mediated costimulation in CD8(+) but not CD4(+) T cells lacking p27(Kip1). These
      data highlight a previously unappreciated difference in the way CD28 signaling is
      coupled to the core cell cycle machinery in these two T cell subsets.

PMID- 15728452
TI  - Cutting edge: regulation of T cell trafficking and primary immune responses by
      sphingosine 1-phosphate receptor 1.
AB  - Signaling by sphingosine 1-phosphate (S1P) through its receptor S1P(1) has
      recently been shown to promote thymocyte egress. In the periphery, S1P(1) is
      expressed on naive T cells but lost upon T cell activation. To determine the
      significance of S1P(1) down-regulation and function of S1P(1) in peripheral T
      cells, we developed transgenic mice that constitutively express S1P(1) in T
      cells. Mature T cells from these mice exhibited enhanced chemotactic response
      toward S1P, and preferentially distributed to the blood rather than secondary
      lymphoid organs. S1P(1)-transgenic mice showed significant delay in the onset of
      experimental autoimmune encephalomyelitis, and had defective contact
      hypersensitivity reaction and local Ag-induced responses. These impairments were
      associated with reduced numbers of Ag-activated T cells in the draining lymph
      nodes. Our studies demonstrate that S1P(1) signaling affects systemic trafficking
      of peripheral T cells and immune responses and highlight that levels of S1P(1)
      expression represent an important mechanism of immune regulation.

PMID- 15728453
TI  - Cutting edge: back to "one-way" germinal centers.
AB  - The present status of germinal center (GC) research is revisited using in silico
      simulations based on recent lymphocyte motility data in mice. The generally
      adopted view of several rounds of somatic hypermutations and positive selection
      is analyzed with special emphasis on the spatial organization of the GC reaction.
      We claim that the development of dark zones is not necessary for successful GC
      reactions to develop. We find that a recirculation of positively selected
      centrocytes to the dark zone is rather unlikely. Instead we propose a scenario
      that combines a multiple-step mutation and selection concept with a "one-way" GC
      in the sense of cell migration.

PMID- 15728455
TI  - IFN-alpha induces early lethal lupus in preautoimmune (New Zealand Black x New
      Zealand White) F1 but not in BALB/c mice.
AB  - Recent studies indicate that IFN-alpha is involved in pathogenesis of systemic
      lupus erythematosus. However, direct proof that IFN-alpha is not only necessary,
      but also sufficient to induce lupus pathogenicity is lacking. In this study, we
      show that in vivo adenovector-mediated delivery of murine IFN-alpha results in
      preautoimmune (New Zealand Black (NZB) x New Zealand White (NZW))F(1), but not in
      normal, mice, in a rapid and severe disease with all characteristics of systemic
      lupus erythematosus. Anti-dsDNA Abs appeared as soon as day 10 after initiation
      of IFN-alpha treatment. Proteinuria and death caused by glomerulonephritis
      occurred in all treated mice within, respectively, approximately 9 and
      approximately 18 wk, at a time when all untreated (NZB x NZW)F(1) did not show
      any sign of disease. IFN-alpha in vivo induced an overexpression of B lymphocyte
      stimulator in circulation at similar levels in both the preautoimmune and the
      normal mouse strains. All effects elicited by IFN-alpha were dose dependent. (NZB
      x NZW)F(1) infused with purified murine IFN-alpha also showed acceleration of
      lupus. Thus, prolonged expression of IFN-alpha in vivo induces early lethal lupus
      in susceptible animals.

PMID- 15728456
TI  - Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining
      the expression of Hes-1, a target of the Notch pathway.
AB  - Polycomb group (PcG) proteins play a role in the maintenance of cellular identity
      throughout many rounds of cell division through the regulation of gene
      expression. In this report we demonstrate that the loss of the PcG gene mel-18
      impairs the expansion of the most immature T progenitor cells at a stage before
      the rearrangement of the TCR beta-chain gene in vivo and in vitro. This
      impairment of these T progenitors appears to be associated with increased
      susceptibility to cell death. We also show that the expression of Hes-1, one of
      the target genes of the Notch signaling pathway, is drastically down-regulated in
      early T progenitors isolated from mel-18(-/-) mice. In addition, mel-18(-/-) T
      precursors could not maintain the Hes-1 expression induced by Delta-like-1 in
      monolayer culture. Collectively, these data indicate that mel-18 contributes to
      the maintenance of the active state of the Hes-1 gene as a cellular memory
      system, thereby supporting the expansion of early T progenitors.

PMID- 15728454
TI  - Cutting edge: IL-4 induces suppressor of cytokine signaling-3 expression in B
      cells by a mechanism dependent on activation of p38 MAPK.
AB  - The signaling cascade initiated by IL-4 is classically divisible into two major
      pathways: one mediated by STAT6, and the other by insulin receptor substrates-1
      and -2 via activation of PI3K. In murine splenic B cells, the suppressor of
      cytokine signaling (SOCS)3 is inducible by IL-4 via a mechanism independent of
      STAT6 and PI3K. SOCS3 expression increases 9-fold within 5 h of IL-4 treatment.
      This induction occurs normally in B cells deficient in STAT6 and is unaffected by
      pretreatment with the PI3K inhibitor wortmannin, or with the ERK pathway
      inhibitor, PD98059. However, the IL-4 induction of SOCS3 is blocked by inhibitors
      of either the JNK or p38 MAPK pathways (SP600125 and SB203580, respectively).
      Direct examination of these pathways reveals rapid, IL-4-directed activation of
      p38 MAPK, uncovering a previously unappreciated pathway mediating IL-4 signal
      transduction.

PMID- 15728457
TI  - Naive, effector, and memory T lymphocytes efficiently scan dendritic cells in
      vivo: contact frequency in T cell zones of secondary lymphoid organs does not
      depend on LFA-1 expression and facilitates survival of effector T cells.
AB  - Contact between T cells and dendritic cells (DCs) is required for their
      subsequent interaction leading to the induction of adaptive immune responses.
      Quantitative data regarding the contact frequencies of T cell subsets in
      different lymphoid organs and species are lacking. Therefore, naive, effector,
      and memory CD4 T cells were injected into rats in absence of the cognate Ag, and
      0.5-96 h later, spleen, lymph nodes, and Peyer's patches were removed.
      Cryosections were analyzed for contact between donor T cells and endogenous DCs
      in the T cell zone, and donor cell proliferation. More than 60% of injected naive
      CD4 T cells were in contact with endogenous DCs at all time points and in all
      organs analyzed. Surprisingly, we were unable to detect any differences between
      naive, effector, and memory CD4 T cells despite different expression levels of
      surface molecules. In addition, contact frequency was similar for T cells in
      lymphoid organs of rats, mice, and humans; it was unaffected by the absence of
      LFA-1 (CD11a/CD18), and sustained effector T cells in an activated state. Thus,
      the architecture of the T cell zone rather than expression patterns of surface
      molecules determines the contact efficiency between T cells and DCs in vivo.

PMID- 15728458
TI  - Thymic anlage is colonized by progenitors restricted to T, NK, and dendritic cell
      lineages.
AB  - It remains controversial whether the thymus-colonizing progenitors are committed
      to the T cell lineage. A major problem that has impeded the characterization of
      thymic immigrants has been that the earliest intrathymic progenitors thus far
      identified do not necessarily represent the genuine thymic immigrants, because
      their developmental potential should have been influenced by contact with the
      thymic microenvironment. In the present study, we examined the developmental
      potential of the ontogenically earliest thymic progenitors of day 11 murine
      fetus. These cells reside in the surrounding mesenchymal region and have not
      encountered thymic epithelial components. Flow cytometric and immunohistochemical
      analyses demonstrated that these cells are exclusively Lin(-)c-kit(+)IL-7R(+).
      Limiting dilution analyses disclosed that the progenitors with T cell potential
      were abundant, while those with B cell potential were virtually absent in the
      region of day 11 thymic anlage. Clonal analyses reveled that they are restricted
      to T, NK, and dendritic cell lineages. Each progenitor was capable of forming a
      large number of precursors that may clonally accommodate highly diverse TCRbeta
      chains. These results provide direct evidence that the progenitors restricted to
      the T/NK/dendritic cell lineage selectively immigrate into the thymus.

PMID- 15728459
TI  - Antiangiogenic drugs synergize with a membrane macrophage colony-stimulating
      factor-based tumor vaccine to therapeutically treat rats with an established
      malignant intracranial glioma.
AB  - Combining a T9/9L glioma vaccine, expressing the membrane form of M-CSF, with a
      systemic antiangiogenic drug-based therapy theoretically targeted toward growth
      factor receptors within the tumor's vasculature successfully treated >90% of the
      rats bearing 7-day-old intracranial T9/9L gliomas. The antiangiogenic drugs
      included (Z)-3-[4-(dimethylamino)benzylidenyl]indolin-2-one (a platelet-derived
      growth factor receptor beta and a fibroblast growth factor receptor 1 kinase
      inhibitor) and oxindole (a vascular endothelial growth factor receptor 2 kinase
      inhibitor). A total of 20-40% of the animals treated with the antiangiogenic
      drugs alone survived, while all nontreated controls and tumor vaccine-treated
      rats died within 40 days. In vitro, these drugs inhibited endothelial cells from
      proliferating in response to the angiogenic factors produced by T9/9L glioma
      cells and prevented endothelial cell tubulogenesis. FITC-labeled tomato lectin
      staining demonstrated fewer and constricted blood vessels within the intracranial
      tumor after drug therapy. Magnetic resonance imaging demonstrated that the
      intracranial T9 glioma grew much slower in the presence of these antiangiogenic
      drugs. These drugs did not affect in vitro glioma cell growth nor T cell
      mitogenesis. Histological analysis revealed that the tumor destruction occurred
      at the margins of the tumor, where there was a heavy lymphocytic infiltrate. Real
      time PCR showed more IL-2-specific mRNA was present within the gliomas in the
      vaccinated rats treated with the drugs. Animals that rejected the established
      T9/9L glioma by the combination therapy proved immune against an intracranial
      rechallenge by T9/9L glioma, but showed no resistance to an unrelated MADB106
      breast cancer.

PMID- 15728460
TI  - Regulated folding of tyrosinase in the endoplasmic reticulum demonstrates that
      misfolded full-length proteins are efficient substrates for class I processing
      and presentation.
AB  - Short-lived protein translation products have been proposed to be the principal
      substrates that enter the class I MHC processing and presentation pathway.
      However, the biochemical nature of these substrates is poorly defined. Whether
      the major processing substrates are misfolded full-length proteins, or
      alternatively, aberrantly initiated or truncated polypeptides still remains to be
      addressed. To examine this, we used melanoma in which one-third of wild-type
      tyrosinase molecules were correctly folded and localized beyond the Golgi, while
      the remainder were present in the endoplasmic reticulum in an unfolded/misfolded
      state. Increasing the efficiency of tyrosinase folding using chemical chaperones
      led to a reduction in the level of substrate available to the proteasome and
      decreased the expression of a tyrosinase-derived epitope. Conversely, in
      transfectants expressing tyrosinase mutants that are completely misfolded, both
      proteasome substrate and epitope presentation were significantly enhanced.
      Proteasome substrate availability was a consequence of misfolding and not simply
      due to retention in the endoplasmic reticulum. Thus, the extent of
      folding/misfolding of a full-length protein is an important determinant of the
      level of epitope presentation.

PMID- 15728461
TI  - Progressive and controlled development of mouse dendritic cells from Flt3+CD11b+
      progenitors in vitro.
AB  - Dendritic cells (DC) represent key regulators of the immune system, yet their
      development from hemopoietic precursors is poorly defined. In this study, we
      describe an in vitro system for amplification of a Flt3(+)CD11b(+) progenitor
      from mouse bone marrow with specific cytokines. Such progenitor cells develop
      into both CD11b(+) and CD11b(-) DC, and CD8alpha(+) and CD8alpha(-) DC in vivo.
      Furthermore, with GM-CSF, these progenitors synchronously differentiated into
      fully functional DC in vitro. This two-step culture system yields homogeneous
      populations of Flt3(+)CD11b(+) progenitor cells in high numbers and allows
      monitoring the consecutive steps of DC development in vitro under well-defined
      conditions. We used phenotypic and functional markers and transcriptional
      profiling by DNA microarrays to study the Flt3(+)CD11b(+) progenitor and
      differentiated DC. We report here on an extensive analysis of the surface Ag
      expression of Flt3(+)CD11b(+) progenitor cells and relate that to surface Ag
      expression of hemopoietic stem cells. Flt3(+)CD11b(+) progenitors studied exhibit
      a broad overlap of surface Ags with stem cells and express several stem cell Ags
      such as Flt3, IL-6R, c-kit/SCF receptor, and CD93/AA4.1, CD133/AC133, and
      CD49f/integrin alpha(6). Thus, Flt3(+)CD11b(+) progenitors express several stem
      cell surface Ags and develop into both CD11b(+) and CD11b(-) DC, and CD8alpha(+)
      and CD8alpha(-) DC in vivo, and thus into both of the main conventional DC
      subtypes.

PMID- 15728462
TI  - The fate of low affinity tumor-specific CD8+ T cells in tumor-bearing mice.
AB  - A major challenge in tumor immunology is how best to activate the relatively low
      avidity self-specific and tumor-specific T cells that are available in the self
      tolerant repertoire. To address this issue, we produced a TCR transgenic mouse
      expressing a class I-restricted hemagglutinin (HA)-specific TCR (clone 1 TCR)
      derived from a mouse that expressed HA as a self-Ag in the insulin-producing beta
      cells of the pancreatic islets (InsHA) mice. Upon transfer of clone 1 TCR CD8(+)
      T cells into InsHA mice, very few cells were activated by cross-presented HA,
      indicating that the cells were retained in InsHA mice because they ignored the
      presence of Ag, and not because they were functionally inactivated by anergy or
      tuning. Upon transfer into recipient mice in which HA is expressed at high
      concentrations as a tumor-associated Ag in spontaneously arising insulinomas (RIP
      Tag2-HA mice), a high proportion of clone 1 cells were activated when they
      encountered cross-presented tumor Ag in the pancreatic lymph nodes. However, the
      activated cells exhibited very weak effector function and were soon tolerized.
      The few activated cells that did migrate to the tumor were unable to delay tumor
      progression. However, when HA-specific CD4 helper cells were cotransferred with
      clone 1 cells into RIP-Tag2-HA recipients and the mice were vaccinated with
      influenza, clone 1 cells were found to exert a significant level of effector
      function and could delay tumor growth. This tumor model should prove of great
      value in identifying protocols that can optimize the function of low avidity
      tumor-specific T cells.

PMID- 15728463
TI  - IFN regulatory factor-4 and -8 govern dendritic cell subset development and their
      functional diversity.
AB  - Dendritic cells (DCs) are bone marrow (BM)-derived APCs central to both innate
      and adaptive immunity. DCs are a heterogeneous cell population composed of
      multiple subsets with diverse functions. The mechanism governing the generation
      of multiple DC subsets is, however, poorly understood. In this study we
      investigated the roles of closely related transcription factors, IFN regulatory
      factor (IRF)-4 and IRF-8, in DC development by analyzing IRF-4(-/-), IRF-8(-/-),
      and IRF-4(-/-)IRF-8(-/-) (double-knockout) mice. We found that IRF-4 is required
      for the generation of CD4(+) DCs, whereas IRF-8 is, as reported previously,
      essential for CD8alpha(+) DCs. Both IRFs support the development of CD4(
      )CD8alpha(-) DCs. IRF-8 and, to a lesser degree, IRF-4 contribute to plasmacytoid
      DC (PDC) development. Thus, the two IRFs together regulate the development of all
      conventional DCs as well as PDCs. Consistent with these findings, IRF-4, but not
      IRF-8, was expressed in CD4(+) DCs, whereas only IRF-8 was expressed in
      CD8alpha(+) DCs. CD4(-)CD8alpha(-) DCs and PDCs expressed both IRFs. We also
      demonstrate in vitro that GM-CSF-mediated DC differentiation depends on IRF-4,
      whereas Fms-like tyrosine kinase 3 ligand-mediated differentiation depends mainly
      on IRF-8. Gene transfer experiments with double-knockout BM cells showed that
      both IRFs have an overlapping activity and stimulate a common process of DC
      development. Nonetheless, each IRF also possesses a distinct activity to
      stimulate subset-specific gene expression, leading to the generation of
      functionally divergent DCs. Together, IRF-4 and IRF-8 serve as a backbone of the
      molecular program regulating DC subset development and their functional
      diversity.

PMID- 15728464
TI  - CXC chemokine ligand 12-induced focal adhesion kinase activation and segregation
      into membrane domains is modulated by regulator of G protein signaling 1 in pro-B
      cells.
AB  - CXCL12-induced chemotaxis and adhesion to VCAM-1 decrease as B cells
      differentiate in the bone marrow. However, the mechanisms that regulate
      CXCL12/CXCR4-mediated signaling are poorly understood. We report that after
      CXCL12 stimulation of progenitor B cells, focal adhesion kinase (FAK) and PI3K
      are inducibly recruited to raft-associated membrane domains. After CXCL12
      stimulation, phosphorylated FAK is also localized in membrane domains. The
      CXCL12/CXCR4-FAK pathway is membrane cholesterol dependent and impaired by
      metabolic inhibitors of G(i), Src family, and the GTPase-activating protein,
      regulator of G protein signaling 1 (RGS1). In the bone marrow, RGS1 mRNA
      expression is low in progenitor B cells and high in mature B cells, implying
      developmental regulation of CXCL12/CXCR4 signaling by RGS1. CXCL12-induced
      chemotaxis and adhesion are impaired when FAK recruitment and phosphorylation are
      inhibited by either membrane cholesterol depletion or overexpression of RGS1 in
      progenitor B cells. We conclude that the recruitment of signaling molecules to
      specific membrane domains plays an important role in CXCL12/CXCR4-induced
      cellular responses.

PMID- 15728465
TI  - CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper
      cells and hindered by naturally occurring T regulatory cells.
AB  - CD4(+) T cells control the effector function, memory, and maintenance of CD8(+) T
      cells. Paradoxically, we found that absence of CD4(+) T cells enhanced adoptive
      immunotherapy of cancer when using CD8(+) T cells directed against a persisting
      tumor/self-Ag. However, adoptive transfer of CD4(+)CD25(-) Th cells (Th cells)
      with tumor/self-reactive CD8(+) T cells and vaccination into CD4(+) T cell
      deficient hosts induced autoimmunity and regression of established melanoma.
      Transfer of CD4(+) T cells that contained a mixture of Th and CD4(+)CD25(+) T
      regulatory cells (T(reg) cells) or T(reg) cells alone prevented effective
      adoptive immunotherapy. Maintenance of CD8(+) T cell numbers and function was
      dependent on Th cells that were capable of IL-2 production because therapy failed
      when Th cells were derived from IL-2(-/-) mice. These findings reveal that Th
      cells can help break tolerance to a persisting self-Ag and treat established
      tumors through an IL-2-dependent mechanism, but requires simultaneous absence of
      naturally occurring T(reg) cells to be effective.

PMID- 15728466
TI  - The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and
      NF-kappa B (RelA) independently of its role in filamentous actin polymerization
      and actin cytoskeletal rearrangement.
AB  - Effector functions mediated by NK cells involve cytotoxicity and transcription
      dependent production and release of cytokines and chemokines. Although the
      JAK/STAT pathway mediates lymphokine-induced transcriptional regulation in NK
      cells, very little is known about transcriptional regulation induced during cell
      cell contact. We demonstrate that the Wiskott-Aldrich syndrome protein (WASp) is
      an important component for integration of signals leading to nuclear
      translocation of NFAT2 and NF-kappaB (RelA) during cell-cell contact and NKp46
      dependent signaling. This WASp function is independent of its known role in F
      actin polymerization and cytoskeletal rearrangement. Absence of WASp results in
      decreased accumulation of calcineurin, WASp-interacting protein, and molecules
      upstream of calcium mobilization, i.e., activated ZAP70 and phospholipase C
      gamma1, in the disorganized NK cell immune synapse. Production of GM-CSF, but not
      IFN-gamma, is decreased, while natural cytotoxicity of Wiskott-Aldrich syndrome
      NK cells is maintained. Our results indicate that WASp independently regulates
      its dual functions, i.e., actin cytoskeletal remodeling and transcription in NK
      cells.

PMID- 15728467
TI  - Natural killer dendritic cells have both antigen presenting and lytic function
      and in response to CpG produce IFN-gamma via autocrine IL-12.
AB  - We have isolated rare cells bearing the NK cell surface marker NK1.1, as well as
      the dendritic cell (DC) marker CD11c, from the spleen, liver, lymph nodes, and
      thymus of normal mice. These cells possess both NK cell and DC function because
      they can lyse tumor cells and subsequently present Ags to naive Ag-specific T
      cells. Interestingly, in response to IL-4 plus either IL-2 or CpG, NKDC produce
      more IFN-gamma than do DC, or even NK cells. We determined that CpG, but not IL
      2, induces NKDC to secrete IFN-gamma via the autocrine effects of IL-12. In vivo,
      CpG dramatically increases the number of NKDC. Furthermore, NKDC induce greater
      Ag-specific T cell activation than do DC after adoptive transfer. Their unique
      ability to lyse tumor cells, present Ags, and secrete inflammatory cytokines
      suggests that NKDC may play a crucial role in linking innate and adaptive
      immunity.

PMID- 15728468
TI  - Activated human B lymphocytes express cyclooxygenase-2 and cyclooxygenase
      inhibitors attenuate antibody production.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment
      of inflammatory diseases and target cyclooxygenases 1 and 2 (Cox-1, Cox-2) that
      are responsible for PG production. Newer Cox-2-selective drugs have been heavily
      prescribed to quench inflammation. Little is known about whether or not these
      drugs influence human B lymphocytes and their ability to produce Ab. We report
      herein that activated human B cells not only highly express Cox-2 and produce
      PGs, but that the NSAID indomethacin and Cox-2-selective drugs profoundly inhibit
      the ability of human B cells to produce IgG and IgM in vitro. Human blood B cells
      highly express Cox-2 mRNA and protein and produce PGs after activation with
      CD40L, pansorbin, or CD40L plus BCR engagement. Cox-2 is also highly expressed by
      human tonsil B cells, as shown by immunohistochemistry. Cox-inhibiting drugs
      modestly affect purified B cell proliferation but profoundly reduce Ab
      production. The ability of whole blood to produce IgM and IgG following
      stimulation is also strongly inhibited. In support that Cox-2 plays a seminal
      role in B lymphocyte Ab production, Cox-2 knockout mice have 64% less IgM and 35%
      less IgG than normal littermate controls. These findings support that NSAIDs and
      the new Cox-2-selective drugs have an unsuspected target, the B cell, and
      attenuate Ab production in humans. Use of NSAIDs may therefore influence
      autoantibody production in autoimmune diseases and may dampen humoral immunity in
      response to antigenic challenge/vaccination.

PMID- 15728469
TI  - Overexpression of the Runx3 transcription factor increases the proportion of
      mature thymocytes of the CD8 single-positive lineage.
AB  - The Runx family of transcription factors is thought to regulate the
      differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+)
      subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is
      de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates
      Runx3 in CD4 silencing, but does not necessarily prove its role in the
      differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created
      transgenic mice that overexpress Runx3 and analyzed the development of thymocytes
      in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells
      was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells
      were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a
      TCR(high)HSA(low) phenotype. These cells were released from the thymus and
      contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-)
      cells in the spleen. Runx3 overexpression also increased the number of mature
      CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in
      mice with a class I-deficient background, both of which are favorable for
      CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(
      )8(+) lineage. This activity is likely to be due to more than a simple silencing
      of CD4 gene expression.

PMID- 15728470
TI  - The human CD1-restricted T cell repertoire is limited to cross-reactive antigens:
      implications for host responses against immunologically related pathogens.
AB  - The repertoires of CD1- and MHC-restricted T cells are complementary, permitting
      the immune recognition of both lipid and peptide Ags, respectively. To compare
      the breadth of the CD1-restricted and MHC-restricted T cell repertoires, we
      evaluated T cell responses against lipid and peptide Ags of mycobacteria in
      leprosy, comparing tuberculoid patients, who are able to restrict the pathogen,
      and lepromatous patients, who have disseminated infection. The striking finding
      was that in lepromatous leprosy, T cells did not efficiently recognize lipid Ags
      from the leprosy pathogen, Mycobacterium leprae, or the related species,
      Mycobacterium tuberculosis, yet were able to efficiently recognize peptide Ags
      from M. tuberculosis, but not M. leprae. To identify a mechanism for T cell
      unresponsiveness against mycobacterial lipid Ags in lepromatous patients, we used
      T cell clones to probe the species specificity of the Ags recognized. We found
      that the majority of M. leprae-reactive CD1-restricted T cell clones (92%) were
      cross-reactive for multiple mycobacterial species, whereas the majority of M.
      leprae-reactive MHC-restricted T cells were species specific (66%), with a
      limited number of T cell clones cross-reactive (34%) with M. tuberculosis. In
      comparison with the MHC class II-restricted T cell repertoire, the CD1-restricted
      T cell repertoire is limited to recognition of cross-reactive Ags, imparting a
      distinct role in the host response to immunologically related pathogens.

PMID- 15728471
TI  - In vivo manipulation of dendritic cells overcomes tolerance to unmodified tumor
      associated self antigens and induces potent antitumor immunity.
AB  - Most tumor-associated Ags are self proteins that fail to elicit a T cell response
      as a consequence of immune tolerance. Dendritic cells (DCs) generated ex vivo
      have been used to break tolerance against such self Ags; however, in vitro
      manipulation of DCs is cumbersome and difficult to control, resulting in vaccines
      of variable potency. To address this problem we developed a method for loading
      and activating DCs, in situ, by first directing sufficient numbers of DCs to
      peripheral tissues using Flt3 ligand and then delivering a tumor-associated Ag
      and oligonucleotide containing unmethylated CG motifs to these tissues. In this
      study, we show in three different tumor models that this method can overcome
      tolerance and induce effective antitumor immunity. Vaccination resulted in the
      generation of CD8(+) T and NK cell effectors that mediated durable tumor
      responses without attacking normal tissues. These findings demonstrate that
      unmodified tumor-associated self Ags can be targeted to DCs in vivo to induce
      potent systemic antitumor immunity.

PMID- 15728472
TI  - Tumor-induced apoptosis of human IL-2-activated NK cells: role of natural
      cytotoxicity receptors.
AB  - We provide evidence that tumor cells can induce apoptosis of NK cells by engaging
      the natural cytotoxicity receptors (NCR) NKp30, NKp44, and NKp46. Indeed, the
      binding between NCR on NK cells and their putative ligands on tumor target cells
      led to NK cell apoptosis, and this event was abolished by blocking NCR/NCR-ligand
      interaction by anti-NCR-specific mAbs. The engagement of NCR induced up
      regulation of Fas ligand (FasL) mRNA, FasL protein synthesis, and release. In
      turn, FasL interacting with Fas at NK cell surface causes NK cell suicide, as
      apoptosis of NK cells was inhibited by blocking FasL/Fas interaction with
      specific mAbs. Interestingly, NK cell apoptosis, but not killing of tumor target
      cells, is inhibited by cyclosporin A, suggesting that apoptosis and cytolysis are
      regulated by different biochemical pathways. These findings indicate that NCR are
      not only triggering molecules essential for antitumor activity, but also surface
      receptors involved in NK cell suicide.

PMID- 15728473
TI  - Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by
      antigen-specific CD4+ regulatory T cells.
AB  - CD4(+) regulatory T (Treg) cells play an important role in the maintenance of
      immunological self-tolerance by suppressing immune responses against autoimmune
      diseases and cancer. Yet very little is known about the natural antigenic ligands
      that preferentially activate CD4(+) Treg cells. Here we report the establishment
      of tumor-specific CD4(+) Treg cell clones from tumor-infiltrating lymphocytes
      (TILs) of cancer patients, and the identification of an Ag recognized by Treg
      cells (ARTC1) gene encoding a peptide ligand recognized by tumor-specific TIL164
      CD4(+) Treg cells. The mutations in a gene encoding an ARTC1 in 164mel tumor
      cells resulted in the translation of a gene product containing the peptide ligand
      recognized by CD4(+) Treg cells. ARTC1 peptide-activated CD4(+) Treg cells
      suppress the physiological function (proliferation and IL-2 secretion) of
      melanoma-reactive T cells. Furthermore, 164mel tumor cells, but not tumor lysates
      pulsed on B cells, were capable of activating TIL164 CD4(+) Treg cells. These
      results suggest that tumor cells may uniquely present an array of peptide ligands
      that preferentially recruit and activate CD4(+) Treg cells in sites where tumor
      specific self-peptide is expressed, leading to the induction of local and tumor
      specific immune suppression.

PMID- 15728474
TI  - Mismatched antigen prepares gamma delta T cells for suppression of airway
      hyperresponsiveness.
AB  - Gammadelta T cells suppress airway hyperresponsiveness (AHR) induced in allergen
      challenged mice but it is not clear whether the suppression is allergen specific.
      The AHR-suppressive cells express TCR-Vgamma4. To test whether the suppressive
      function must be induced, we adoptively transferred purified Vgamma4(+) cells
      into gammadelta T cell-deficient and OVA-sensitized and -challenged recipients
      (B6.TCR-Vgamma4(-/-)/6(-/-)) and measured the effect on AHR. Vgamma4(+)
      gammadelta T cells isolated from naive donors were not AHR-suppressive, but
      Vgamma4(+) cells from OVA-stimulated donors suppressed AHR. Suppressive
      Vgamma4(+) cells could be isolated from lung and spleen. Their induction in the
      spleen required sensitization and challenge. In the lung, their function was
      induced by airway challenge alone. Induction of the suppressors was associated
      with their activation but it did not alter their ability to accumulate in the
      lung. Vgamma4(+) gammadelta T cells preferentially express Vdelta4 and -5 but
      their AHR-suppressive function was not dependent on these Vdeltas. Donor
      sensitization and challenge not only with OVA but also with two unrelated
      allergens (ragweed and BSA) induced Vgamma4(+) cells capable of suppressing AHR
      in the OVA-hyperresponsive recipients, but the process of sensitization and
      challenge alone (adjuvant and saline only) was not sufficient to induce
      suppressor function, and LPS as a component of the allergen was not essential. We
      conclude that AHR-suppressive Vgamma4(+) gammadelta T cells require induction.
      They are induced by allergen stimulation, but AHR suppression by these cells does
      not require their restimulation with the same allergen.

PMID- 15728475
TI  - Platelet factor 4 differentially modulates CD4+CD25+ (regulatory) versus CD4+CD25
      (nonregulatory) T cells.
AB  - Active suppression mediated by CD4(+)CD25(+) T regulatory (Tr) cells plays an
      important role in the down-regulation of T cell responses to both foreign and
      self-Ags. Platelet factor 4 (PF4), a platelet-derived CXC chemokine, has been
      shown to strongly inhibit T cell proliferation as well as IFN-gamma and IL-2
      release by isolated T cells. In this report we show that human PF4 stimulates
      proliferation of the naturally anergic human CD4(+)CD25(+) Tr cells while
      inhibiting proliferation of CD4(+)CD25(-) T cells. In coculture experiments we
      found that CD4(+)CD25(+) Tr cells exposed to PF4 lose the ability to inhibit the
      proliferative response of CD4(+)CD25(-) T cells. Our findings suggest that human
      PF4, by inducing Tr cell proliferation while impairing Tr cell function, may play
      a previously unrecognized role in the regulation of human immune responses.
      Because platelets are the sole source of PF4 in the circulation, these findings
      may be relevant to the pathogenesis of certain immune-mediated disorders
      associated with platelet activation, such as heparin-induced thrombocytopenia and
      autoimmune thrombocytopenic purpura.

PMID- 15728476
TI  - CD38 signaling regulates B lymphocyte activation via a phospholipase C (PLC)
      gamma 2-independent, protein kinase C, phosphatidylcholine-PLC, and phospholipase
      D-dependent signaling cascade.
AB  - The CD38 cell surface receptor is a potent activator for splenic, B lymphocytes.
      The molecular mechanisms regulating this response, however, remain incompletely
      characterized. Activation of the nonreceptor tyrosine kinase, Btk, is essential
      for CD38 downstream signaling function. The major Btk-dependent substrate in B
      cells, phospholipase C-gamma2 (PLC-gamma2), functions to generate the key
      secondary messengers, inositol-1,4,5 trisphosphate and diacylglycerol.
      Surprisingly, CD38 ligation results in no detectable increase in phosphoinositide
      metabolism and only a minimal increase in cytosolic calcium. We hypothesized that
      Btk functioned independently of PLC-gamma2 in the CD38 signaling pathway.
      Accordingly, we demonstrate that CD38 cross-linking does not result in the
      functional phosphorylation of PLC-gamma2 nor an increase in inositol-1,4,5
      trisphosphate production. Furthermore, splenic B cells exhibit a normal CD38
      mediated, proliferative response in the presence of the phosphoinositide-PLC
      inhibitor, U73122. Conversely, protein kinase C (PKC) beta-deficient mice, or PKC
      inhibitors, indicated the requirement for diacylglycerol-dependent PKC isoforms
      in this pathway. Loss of PKC activity blocked CD38-dependent, B cell
      proliferation, NF-kappaB activation, and subsequent expression of cyclin-D2.
      These results suggested that an alternate diacylglycerol-producing phospholipase
      must participate in CD38 signaling. Consistent with this idea, CD38 increased the
      enzymatic activity of the phosphatidylcholine (PC)-metabolizing enzymes, PC-PLC
      and phospholipase D. The PC-PLC inhibitor, D609, completely blocked CD38
      dependent B cell proliferation, IkappaB-alpha degradation, and cyclin-D2
      expression. Analysis of Btk mutant B cells demonstrated a partial requirement for
      Btk in the activation of both enzymes. Taken together, these data demonstrate
      that CD38 initiates a novel signaling cascade leading to Btk-, PC-PLC-, and
      phospholipase D-dependent, PLC-gamma2-independent, B lymphocyte activation.

PMID- 15728477
TI  - Differential effects of IL-21 during initiation and progression of autoimmunity
      against neuroantigen.
AB  - The cytokine IL-21 is closely related to IL-2 and IL-15, a cytokine family that
      uses the common gamma-chain for signaling. IL-21 is expressed by activated CD4(+)
      T cells. We examined the role of IL-21 in the autoimmune disease experimental
      autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis.
      IL-21 administration before induction of EAE with a neuroantigen, myelin
      oligodendrocyte glycoprotein peptide 35-55, and adjuvant enhanced the
      inflammatory influx into the CNS, as well as the severity of EAE. Autoreactive T
      cells purified from IL-21-treated mice transferred more severe EAE than did the
      control encephalitogenic T cells. No such effects were observed when IL-21 was
      administered after EAE progressed. Additional studies demonstrated that IL-21
      given before the induction of EAE boosted NK cell function, including secretion
      of IFN-gamma. Depletion of NK cells abrogated the effect of IL-21. Therefore, IL
      21, by affecting NK cells, has differential effects during the initiation and
      progression of autoimmune responses against neuroantigens.

PMID- 15728478
TI  - Two structurally related rat Ly49 receptors with opposing functions (Ly49
      stimulatory receptor 5 and Ly49 inhibitory receptor 5) recognize nonclassical MHC
      class Ib-encoded target ligands.
AB  - The Ly49 family of lectin-like receptors in rodents includes both stimulatory and
      inhibitory members. Although NK alloreactivity in mice is regulated primarily by
      inhibitory Ly49 receptors, in rats activating Ly49 receptors are equally
      important. Previous studies have suggested that activating rat Ly49 receptors are
      triggered by polymorphic ligands encoded within the nonclassical class Ib region
      of the rat MHC, RT1-CE/N/M, while inhibitory Ly49 receptors bind to widely
      expressed classical class Ia molecules encoded from the RT1-A region. To further
      investigate rat Ly49-mediated regulation of NK alloreactivity, we report in this
      study the identification and characterization of two novel paired Ly49 receptors
      that we have termed Ly49 inhibitory receptor 5 (Ly49i5) and Ly49 stimulatory
      receptor 5 (Ly49s5). Using a new mAb (mAb Fly5), we showed that Ly49i5 is an
      inhibitory receptor that recognizes ligands encoded within the class Ib region of
      the u and l haplotypes, while the structurally related Ly49s5 is an activating
      receptor that recognizes class Ib ligands of the u haplotype. Ly49s5 is
      functionally expressed in the high NK-alloresponder PVG strain, but not in the
      low alloresponder BN strain, in which it is a pseudogene. Ly49s5 is hence not
      responsible for the striking anti-u NK alloresponse previously described in BN
      rats (haplotype n), which results from repeated alloimmunizations with u
      haplotype cells. The present studies support the notion of a complex regulation
      of rat NK alloreactivity by activating and inhibitory Ly49 members, which may be
      highly homologous in the extracellular region and bind similar class Ib-encoded
      target ligands.

PMID- 15728479
TI  - Inhibition of granulocyte-macrophage colony-stimulating factor signaling and
      microglial proliferation by anti-CD45RO: role of Hck tyrosine kinase and
      phosphatidylinositol 3-kinase/Akt.
AB  - Increasing evidence suggests that CD45, a transmembrane protein tyrosine
      phosphatase, is an important modulator of macrophage activation. Microglia,
      resident brain macrophages, express CD45 and proliferate under pathologic
      conditions. In this study, we examined the role of CD45 in modulating GM-CSF
      induced proliferation and signal transduction in primary human microglial
      cultures. Soluble, but not immobilized anti-CD45RO induced tyrosine phosphatase
      activity and inhibited GM-CSF-induced microglial proliferation. Microglial
      proliferation was also inhibited by PP2 (Src inhibitor), LY294002 (PI3K
      inhibitor), and U0126 (MEK inhibitor). GM-CSF induced phosphorylation of Jak2,
      Stat5, Hck (the myeloid-restricted Src kinase), Akt, Stat3, and Erk MAPKs in
      microglia. Of these, anti-CD45RO inhibited phosphorylation of Hck and Akt, and
      PP2 inhibited phosphorylation of Hck and Akt. In a macrophage cell line stably
      overexpressing wild-type or kinase-inactive Hck, GM-CSF increased proliferation
      of the control (empty vector) and wild-type but not kinase-inactive cells, and
      this was inhibited by anti-CD45RO. Together, these results demonstrate that, in
      macrophages, Hck tyrosine kinase is activated by GM-CSF, and that Hck plays a
      pivotal role in cell proliferation and survival by activating the PI3K/Akt
      pathway. Ab-mediated activation of macrophage and microglial CD45 tyrosine
      phosphatase may have therapeutic implications for CNS inflammatory diseases.

PMID- 15728480
TI  - IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4
      T cell activation.
AB  - The transcription factor c-Maf plays a critical and selective role in IL-4 gene
      transcription. Little is known about the mechanism that guides c-Maf regulation
      during early T cell activation. We report that IL-6 but not IL-4 or other
      cytokines, rapidly up-regulates c-Maf transcription, as early as 3 h after TCR
      activation in naive CD4(+) T cells. c-Maf induction requires both IL-6- and TCR
      initiated signals, and is independent of IL-4/Stat6 signals. Cyclosporin A and
      FK506, which target calcineurin and thereby inhibit TCR-mediated Ca(2+) signal
      pathways, block IL-6-mediated c-Maf expression. We show that Stat3 binds the c
      maf promoter in CD4 T cells after IL-6 stimulation, and also transactivates the c
      maf promoter in reporter gene assays. IL-6 induces similar c-Maf expression in
      protein kinase Ctheta-deficient CD4(+) T cells. Furthermore, IL-6 enhances IL-4
      gene expression very early after TCR activation in both wild-type and Stat6
      deficient CD4(+) T cells. Our findings suggest that IL-6 plays a unique role in
      initiating c-Maf expression after TCR engagement, and may subsequently regulate
      early IL-4 production and Th2 commitment.

PMID- 15728481
TI  - In vivo and in absence of a thymus, the enforced expression of the Notch ligands
      delta-1 or delta-4 promotes T cell development with specific unique effects.
AB  - The role of Notch signaling in T cell commitment during lymphoid development is
      well established. However, the identity of the ligand that triggers this critical
      signal in vivo is still unclear. By overexpressing Delta-1 and Delta-4 ligands in
      the hemopoietic cells of athymic nu/nu host mice, we demonstrate that, in vivo
      and in the absence of a thymus, Delta-1 or Delta-4 expression is sufficient to
      promote T cell development from the most immature progenitor stages to complete
      maturation of both CD8(+) and CD4(+) alphabeta T cells. The mature T cells
      developing in a Delta-1- or Delta-4-enriched environment express a diverse TCR
      repertoire, are able to proliferate upon in vitro TCR stimulation, but show
      different profiles of cytokine production after in vitro anti-CD3 stimulation.

PMID- 15728482
TI  - Pro-IL-16 regulation in activated murine CD4+ lymphocytes.
AB  - Prior DNA microarray studies suggested that IL-16 mRNA levels decrease following
      T cell activation, a property unique among cytokines. We examined pro-IL-16 mRNA
      and protein expression in resting and anti-CD3 mAb-activated primary murine
      CD4(+) T cells. Consistent with the microarray reports, pro-IL-16 mRNA levels
      fell within 4 h of activation, and this response is inhibited by cyclosporin A.
      Total cellular pro-IL-16 protein also fell, reaching a nadir at 48 h. Pro-IL-16
      comprises a C-terminal cytokine domain and an N-terminal prodomain that are
      cleaved by caspase-3. Pro-IL-16 expressed in transfected tumor cells was
      previously shown to translocate to the nucleus and to promote G(0)/G(1) arrest by
      stabilizing the cyclin-dependent kinase inhibitor p27(Kip1). In the present
      study, we observed increased S-phase kinase-associated protein 2 mRNA expression
      in IL-16 null mice, but basal expression and activation-dependent regulation of
      p27(Kip1) were no different from wild-type mice. Stimulation with anti-CD3 mAb
      induced transiently greater thymidine incorporation in IL-16-deficient CD4(+) T
      cells than wild-type controls, but there was no difference in cell survival or in
      the CFSE dilution profiles. Analysis of CD4(+) T cell proliferation in vivo using
      BrdU labeling similarly failed to identify a hyperproliferative phenotype in T
      cells lacking IL-16. These data demonstrate that pro-IL-16 mRNA and protein
      expression are dynamically regulated during CD4(+) T cell activation by a
      calcineurin-dependent mechanism, and that pro-IL-16 might influence T cell cycle
      regulation, although not in a dominant manner.

PMID- 15728483
TI  - Different diabetogenic potential of autoaggressive CD8+ clones associated with
      IFN-gamma-inducible protein 10 (CXC chemokine ligand 10) production but not
      cytokine expression, cytolytic activity, or homing characteristics.
AB  - Type 1 diabetes mellitus is an autoimmune disease characterized by T cell
      mediated destruction of the insulin-producing beta cells in the islets of
      Langerhans. From studies in animal models, CD8(+) T cells recognizing
      autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit
      related protein, insulin, or glutamic acid decarboxylase (GAD) are believed to
      play important roles in both the early and late phases of beta cell destruction.
      In this study, we investigated the factors governing the diabetogenic potential
      of autoreactive CD8(+) clones isolated from spleens of NOD mice that had been
      immunized with GAD65(515-524) or insulin B-chain(15-23) peptides. Although these
      two clones were identical in most phenotypic and functional aspects, for example
      cytokine production and killing of autologous beta cells, they differed in the
      expression of IFN-gamma-inducible protein-10, which was only produced at high
      levels by the insulin-specific clone, but not by the GAD65-specific clone, and
      other autoantigen-specific nonpathogenic CD8 T cell clones. Interestingly, upon
      i.p. injection into neonatal mice, only the insulin B-chain(15-23)-reactive
      CD8(+) T clone accelerated diabetes in all recipients after 4 wk, although both
      insulin- and GAD-reactive clones homed to pancreas and pancreatic lymph nodes
      with similar kinetics. Diabetes was associated with increased pancreatic T cell
      infiltration and, in particular, recruitment of macrophages. Thus, secretion of
      IFN-gamma-inducible protein-10 by autoaggressive CD8(+) lymphocytes might
      determine their diabetogenic capacity by affecting recruitment of cells to the
      insulitic lesion.

PMID- 15728484
TI  - Inability of bm14 mice to respond to Theiler's murine encephalomyelitis virus is
      caused by defective antigen presentation, not repertoire selection.
AB  - Natural selection drives diversification of MHC class I proteins, but the
      mechanism by which selection for polymorphism occurs is not known. New variant
      class I alleles differ from parental alleles both in the nature of the CD8 T cell
      repertoire formed and the ability to present pathogen-derived peptides. In the
      current study, we examined whether T cell repertoire differences, Ag presentation
      differences, or both account for differential viral resistance between mice
      bearing variant and parental alleles. We demonstrate that nonresponsive mice have
      inadequate presentation of viral Ag, but have T cell repertoires capable of
      mounting Ag-specific responses. Although previous work suggests a correlation
      between the ability to present an Ag and the ability to generate a repertoire
      responsive to that Ag, we show that the two functions of MHC class I are
      independent.

PMID- 15728485
TI  - The impact of misfolding versus targeted degradation on the efficiency of the MHC
      class I-restricted antigen processing.
AB  - Evidence suggests that most epitopes presented by MHC class I molecules are
      derived from those newly synthesized proteins that are defective due to errors
      during manufacture. We examined epitope production from model cytosolic and
      exocytic proteins modified in various ways. Substrates containing a degradation
      targeting sequence demonstrated very rapid turnover and enhanced epitope
      production, as was the case for substrate retargeted from endoplasmic reticulum
      to cytosol. For less radical alterations, including point mutation and deletion
      and elimination of glycosylation sites, despite detectable changes in folding,
      half-life was only moderately decreased and there were no significant increases
      in epitope production. Puromycin, which causes premature termination of protein
      synthesis, also had no impact upon epitope production. It appears that most
      defective proteins are not rapidly dispensed with and the targeting of most
      nascent proteins for Ag processing is not tied to quality control.

PMID- 15728486
TI  - Constitutively active aryl hydrocarbon receptor expressed specifically in T
      lineage cells causes thymus involution and suppresses the immunization-induced
      increase in splenocytes.
AB  - The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the
      basic helix-loop-helix-PER-ARNT-SIM superfamily. Xenobiotics, such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin, bind the receptor and trigger diverse biological
      reactions. Thymocyte development and T cell-dependent immune reactions are
      sensitive targets of AhR-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity.
      However, the exact role of the AhR in T cells in animals exposed to exogenous
      ligands has not been clarified because indirect effects of activated AhR in other
      cell types cannot be excluded. In this study, we generated transgenic (Tg) mice
      expressing a constitutively active mutant of AhR under the regulation of a T cell
      specific CD2 promoter to examine AhR function in T cells. The mRNAs of the
      constitutively active mutant of AhR and an AhR-induced gene, CYP1A1, were
      expressed in the thymus and spleen of the Tg mice. The transgene expression was
      clearly detected in the thymocytes, CD4, and CD8 T cells, but not in the B cells
      or thymus stromal cells. These Tg mice had a decreased number of thymocytes and
      an increased percentage of CD8 single-positive thymocytes, but their splenocytes
      were much less affected. By contrast, the increase in number of T cells and B
      cells taking place in the spleen after immunization was significantly suppressed
      in the Tg mice. These results clearly show that AhR activation in the T-lineage
      cells is directly involved in thymocyte loss and skewed differentiation. They
      also indicate that AhR activation in T cells and not in B cells suppresses the
      immunization-induced increase in both T cells and B cells.

PMID- 15728487
TI  - Overlapping signaling pathways of sphingosine 1-phosphate and TGF-beta in the
      murine Langerhans cell line XS52.
AB  - TGF-beta has been defined as a key mediator for the induction and maintenance of
      immunological tolerance. Concomitantly, it is essential for homeostasis of
      specialized epithelial dendritic cells, namely, Langerhans cells (LC). Our data
      reveal that TGF-beta induces migration of the immature LC, XS52, a cell line
      expressing the signaling components, TGF-beta type I and II receptors and Smad2,
      3, and 4 mRNA. TGF-beta stimulation induced transient Smad3/4 oligomerization and
      Smad3/DNA binding. Antisense oligonucleotides (ASO) targeting Smad3 abrogated TGF
      beta-induced XS52 chemotaxis, proving the involvement of this Smad protein in the
      TGF-beta-dependent migration. In contrast, the typical CCR6-dependent chemotaxis
      of immature LC induced by CCL20/MIP-3alpha was not affected by Smad3 ASO. Most
      notably, we also identified the lysophospholipid sphingosine 1-phosphate (S1P) as
      a potent chemoattractant for immature LC, which expressed mRNA transcripts of
      lysophospholipid receptors S1P(1-4). Additional experiments with specific ASO
      showed that the Galpha(i)-coupled receptors S1P(1) and S1P(3) were dominantly
      involved in the S1P-induced migration. In contrast, lysophosphatidic acid (LPA),
      also binding to members of the lysophospholipid receptor family, failed to induce
      XS52 migration. Intriguingly, we raised evidence that TGF-beta and S1P signal
      transduction pathways are indeed overlapping, as S1P augmented Smad activation
      and targeted DNA binding with kinetics comparable to TGF-beta. Finally, S1P
      failed to stimulate XS52 chemotaxis when Smad3 protein expression was abrogated.
      Thus, our data indicate a cross-communication between S1P and TGF-beta signaling
      that might be relevant for more than only migratory activities of immature LC.

PMID- 15728488
TI  - Generation of antigen-specific, Foxp3-expressing CD4+ regulatory T cells by
      inhibition of APC proteosome function.
AB  - We tested the hypothesis that immature APC, whose NF-kappaB-signaling pathway and
      thus maturation was blocked by the proteosome inhibitor benzyloxycarbonyl
      isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal (PSI), could be a source of Ag
      specific regulatory T (Treg) cells. DO11.10 CD4(+) T cells that were incubated
      with Ag- and PSI-pulsed APC proliferated poorly, produced less IL-2, IFN-gamma,
      and IL-10 in secondary cultures, and inhibited the response of both naive and
      memory CD4(+) T cells stimulated by Ag-pulsed APC. The generation of PSI-APC Treg
      cells required IL-10 production by APC. PSI-APC Treg cell inhibition required
      cell-cell contact but not IL-10 or TGF-beta. Addition of IL-2 did not reverse,
      but Ab to CTLA-4 did reverse partially the inhibitory effect. Depletion of
      CD25(+) T cells before initial culture with PSI-APC did not affect Treg
      generation. PSI-APC Treg cells expressed high levels of Foxp3, inhibited
      proliferation of naive DO11.10 T cells in vivo, and abrogated colitis driven by a
      memory Th1 response to bacterial-associated Ag. We conclude that NF-kappaB
      blocked, immature APC are able to induce the differentiation of Treg cells that
      can function in vitro and in vivo in an Ag-specific manner.

PMID- 15728489
TI  - Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2
      cytokine expression.
AB  - In the periphery, IL-18 synergistically induces the expression of the Th1
      cytokine IFN-gamma in the presence of IL-12 and the Th2 cytokines IL-5 and IL-13
      in the presence of IL-2. Although the expression of these cytokines has been
      described in the thymus, their role in thymic development and function remains
      uncertain. We report here that freshly isolated thymocytes from C57BL/6 and
      BALB/c mice stimulated in vitro with IL-2-plus-IL-18 or IL-12-plus-IL-18 produce
      large amounts of IFN-gamma and IL-13. Analysis of the thymic subsets, CD4(-)CD8(
      ) (DN), CD4(+)CD8(+), CD4(+)CD8(-), and CD4(-)CD8(+) revealed that IL-18 in
      combination with IL-2 or IL-12 induces IFN-gamma and IL-13 preferentially from DN
      cells. Moreover, DN2 and DN3 thymocytes contained more IFN-gamma(+) cells than
      cells in the later stage of maturation. Additionally, IL-18 in combination with
      IL-2 induces CCR4 (Th2-associated) and CCR5 (Th1-associated) gene expression. In
      contrast, IL-18-plus-IL-12 specifically induced CCR5 expression. The IL-2-plus-IL
      18 or IL-12-plus-IL-18 effect on IFN-gamma and IL-13 expression is dependent on
      Stat4 and NF-kappaB but independent of Stat6, T-bet, or NFAT. Furthermore, IL-12
      plus-IL-18 induces significant thymocyte apoptosis when expressed in vivo or in
      vitro, and this effect is exacerbated in the absence of IFN-gamma. IL-12-plus-IL
      18-stimulated thymocytes can also induce IA-IE expression on cortical and
      medullary thymic epithelial cells in an IFN-gamma-dependent manner. Thus, the
      combination of IL-2, IL-12, and IL-18 can induce phenotypic and functional
      changes in thymocytes that may alter migration, differentiation, and cell death
      of immature T cells inside the thymus and potentially affect the Th1/Th2 bias in
      peripheral immune compartments.

PMID- 15728490
TI  - IgH V-region sequence does not predict the survival fate of human germinal center
      B cells.
AB  - Germinal center (GC) B cell survival fate is governed in part by the outcome of
      successful/failed BCR-mediated interactions with accessory cells. However, the
      extent to which the BCR primary sequence influences such interactions is not
      fully understood. Over 1000 IgV(H)4 family cDNAs were sequenced from living
      (annexin V(-)) and apoptotic (annexin V(+) or from within tingible body
      macrophages) GC B cell fractions from seven tonsils. Results surprisingly
      demonstrate that living and dying GC B cells do not significantly differ in
      IgV(H), D, or J(H) gene segment use; HCDR3 length or positive charge; or mutation
      frequency. Additionally, equivalent IgH cDNA sequences were identified in both
      fractions, suggesting that BCR sequence alone is an unreliable predictor of GC B
      cell survival.

PMID- 15728491
TI  - EBV-induced gene 3 transcription is induced by TLR signaling in primary dendritic
      cells via NF-kappa B activation.
AB  - The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of
      the cytokine IL-27 that controls Th cell development. However, its regulated
      expression in DCs is poorly understood. In the present study we demonstrate that
      EBI3 is expressed in splenic CD8(-), CD8(+), and plasmacytoid DC subsets and is
      induced upon TLR signaling. Cloning and functional analysis of the EBI3 promoter
      using in vivo footprinting and mutagenesis showed that stimulation via TLR2,
      TLR4, and TLR9 transactivated the promoter in primary DCs via NF-kappaB and Ets
      binding sites at -90 and -73 bp upstream of the transcriptional start site,
      respectively. Furthermore, we observed that NF-kappaB p50/p65 and PU.1 were
      sufficient to transactivate the EBI3 promoter in EBI3-deficient 293 cells.
      Finally, induced EBI3 gene expression in DCs was reduced or abrogated in TLR
      2/TLR4, TLR9, and MyD88 knockout mice, whereas both basal and inducible EBI3 mRNA
      levels in DCs were strongly suppressed in NF-kappaB p50-deficient mice. In
      summary, these data suggest that EBI3 expression in DCs is transcriptionally
      regulated by TLR signaling via MyD88 and NF-kappaB. Thus, EBI3 gene transcription
      in DCs is induced rapidly by TLR signaling during innate immune responses
      preceding cytokine driven Th cell development.

PMID- 15728492
TI  - Involvement of TNF and NF-kappa B in the transcriptional control of
      cyclooxygenase-2 expression by IFN-gamma in macrophages.
AB  - IFN-gamma induces cyclooxygenase (COX)-2 expression and PG production in mouse
      macrophage cells. IFN-gamma activates COX-2 promoter-driven transcription.
      Deletion of the IFN sequence regulatory element (ISRE) I -1541/-1522 and ISRE II 
      1215/-1206 sites of the mouse COX-2 promoter minimally decrease this IFN-gamma
      induction. In contrast, deletion of the -965/-150 region from the COX-2 promoter
      abrogated IFN-gamma induction. In this region a NF-kappaB site has been described
      and mutation of this site impairs the induction of the full COX-2 promoter by IFN
      gamma. Moreover, IFN-gamma induction of the COX-2 promoter was also strongly
      reduced by transfection of plasmid encoding the NF-kappaB inhibitor,
      IkappaBalpha. Interestingly, IFN-gamma induction of the COX-2 and PGE(2)
      synthesis was absent in macrophages from TNF(-/-) mice, and neutralizing anti-TNF
      Abs inhibited COX-2 promoter induction by IFN-gamma in RAW 264.7 macrophages.
      Moreover, NF-kappaB activity was induced late after stimulation with IFN-gamma
      correlating with the effect of autocrine TNF, and this NF-kappaB activation was
      absent in macrophages from TNF(-/-) mice. Taken together our results suggest a
      model in which IFN-gamma-induced TNF activates NF-kappaB, which is required for
      full COX-2 expression.

PMID- 15728493
TI  - The Ig kappa 3' enhancer is activated by gradients of chromatin accessibility and
      protein association.
AB  - The Igkappa locus is recombined following initiation of a signaling cascade
      during the early pre-B stage of B cell development. The Ig kappa3' enhancer plays
      an important role in normal B cell development by regulating kappa locus
      activation. Quantitative analyses of kappa3' enhancer chromatin structure by
      restriction endonuclease accessibility and protein association by chromatin
      immunoprecipitation in a developmental series of primary murine B cells and
      murine B cell lines demonstrate that the enhancer is activated progressively
      through multiple steps as cells mature. Moderate kappa3' chromatin accessibility
      and low levels of protein association in pro-B cells are increased substantially
      as the cells progress from pro- to pre-B, then eventually mature B cell stages.
      Chromatin immunoprecipitation assays suggest transcriptional regulators of the
      kappa3' enhancer, specifically PU.1 and IFN regulatory factor-4, exploit enhanced
      accessibility by increasing association as cells mature. Characterization of
      histone acetylation patterns at the kappa3' enhancer and experimental inhibition
      of histone deacetylation suggest changes therein may determine changes in enzyme
      and transcription factor accessibility. This analysis demonstrates kappa
      activation is a multistep process initiated in early B cell precursors before
      Igmu recombination and finalized only after the pre-B cell stage.

PMID- 15728494
TI  - Proteolytic regulation of activated STAT6 by calpains.
AB  - The transcription factor STAT6 plays an important role in cell responses to IL-4.
      Its activation is tightly regulated. STAT6 phosphorylation is associated with
      JAKs, whereas dephosphorylation is associated with specific phosphatases. Several
      studies indicate that proteases can also regulate STAT6. The aim of this study
      was to investigate the nature of these proteases in mouse T cell lines. We found
      that STAT6 was degraded in cell extracts by calcium-dependent proteases. This
      degradation was specifically prevented by calpain inhibitors, suggesting that
      STAT6 was a target for these proteases. This was supported by the cleavage of
      STAT6 by recombinant calpains. The proteolytic regulation of STAT6 was more
      complex in vivo. Calcium signaling was not sufficient to induce STAT6
      degradation. However, treatment of IL-4-stimulated cells with calcium ionophores
      resulted in the absence of phosphorylated STAT6. This effect correlated with the
      loss of STAT6 protein and was prevented by calpain inhibitors. Cytoplasmic
      calpains seemed to be responsible for STAT6 degradation. Calpains can target
      signaling proteins; in this study we found that they can negatively regulate
      activated STAT6.

PMID- 15728495
TI  - Localization of Src homology 2 domain-containing phosphatase 1 (SHP-1) to lipid
      rafts in T lymphocytes: functional implications and a role for the SHP-1 carboxyl
      terminus.
AB  - The protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 1
      (SHP-1) has previously been shown to be a negative regulator of signaling
      mediated via the TCR. A growing body of evidence indicates that the regulated
      localization of proteins within certain membrane subdomains, referred to as lipid
      rafts, is important for the successful transduction of signaling events
      downstream of the TCR. However, considerably less is known about the localization
      of negative regulators during these lipid raft-dependent signaling events. In
      this study we have investigated the subcellular localization of SHP-1 and its
      role in regulation of TCR-mediated signaling. Our studies demonstrate that in a
      murine T cell hybridoma as well as in primary murine thymocytes, a fraction of
      SHP-1 localizes to the lipid rafts, both basally and after TCR stimulation.
      Interestingly, although SHP-1 localized in the nonraft fractions is tyrosine
      phosphorylated, the SHP-1 isolated from the lipid rafts lacks the TCR-induced
      tyrosine phosphorylation, suggesting physical and/or functional differences
      between these two subpopulations. We identify a requirement for the C-terminal
      residues of SHP-1 in optimal localization to the lipid rafts. Although expression
      of SHP-1 that localizes to lipid rafts potently inhibits TCR-mediated early
      signaling events and IL-2 production, the expression of lipid raft-excluded SHP-1
      mutants fails to elicit any of the inhibitory effects. Taken together these
      studies reveal a key role for lipid raft localization of SHP-1 in mediating the
      inhibitory effects on T cell signaling events.

PMID- 15728496
TI  - In situ diversification of the antibody repertoire in chronic Lyme arthritis
      synovium.
AB  - Lyme arthritis is initiated by the tick-borne spirochete, Borrelia burgdorferi.
      In a subset of patients, symptoms do not resolve in response to standard courses
      of antibiotics. Chronic joint inflammation may persist despite spirochetal
      killing, suggesting an autoimmune etiology. The pathogenic mechanisms that
      sustain chronic Lyme arthritis have not been fully elucidated, although T cells
      are believed to play a role. The synovial lesion contains elements of a
      peripheral lymph node, with lymphoid aggregates, plasma cells and follicular
      dendritic cells. An analysis of activated cells at the site of injury could yield
      clues regarding the nature of the response and the identity of potential
      autoantigens. Using laser-capture microdissection, we have isolated plasma cells
      from the joint tissue of chronic Lyme arthritis patients who underwent
      synovectomy. Expressed Ig V regions were amplified by RT-PCR. A majority of
      isolated cells expressed gamma H chains, which is indicative of a class-switched
      response. There were a large number of nucleotide substitutions from germline,
      with a higher fraction of replacement mutations in the CDRs, suggesting a process
      of Ag-driven selection. We have recovered clonal clusters of cells containing
      identical junctions and V(D)J rearrangements. Sequence analysis reveals a
      hierarchy of shared somatic mutations between members of a given clone.
      Intraclonal diversity among plasma cells of close physical proximity points
      toward an ongoing process of diversification and affinity maturation, possibly
      driven by the chronic presence of an autoantigen.

PMID- 15728497
TI  - The two major oligomeric forms of human mannan-binding lectin: chemical
      characterization, carbohydrate-binding properties, and interaction with MBL
      associated serine proteases.
AB  - Mannan-binding lectin (MBL) is an oligomeric C-type lectin assembled from
      homotrimeric structural units that binds to neutral carbohydrates on microbial
      surfaces. It forms individual complexes with MBL-associated serine proteases
      (MASP)-1, -2, -3 and a truncated form of MASP-2 (MAp19) and triggers the lectin
      pathway of complement through MASP-2 activation. To characterize the
      oligomerization state of the two major MBL forms present in human serum, both
      proteins were analyzed by mass spectrometry. Mass values of 228,098 +/- 170 Da
      (MBL-I) and 304,899 +/- 229 Da (MBL-II) were determined for the native proteins,
      whereas reduction of both species yielded a single chain with an average mass of
      25,340 +/- 18 Da. This demonstrates that MBL-I and -II contain 9 and 12 disulfide
      linked chains, respectively, and therefore are trimers and tetramers of the
      structural unit. As shown by surface plasmon resonance spectroscopy, trimeric and
      tetrameric MBL bound to immobilized mannose-BSA and N-acetylglucosamine-BSA with
      comparable K(D) values (2.2 and 0.55 nM and 1.2 and 0.96 nM, respectively).
      However, tetrameric MBL exhibited significantly higher maximal binding capacity
      and lower dissociation rate constants for both carbohydrates. In contrast, no
      significant difference was detected for binding of the recombinant MASPs or MAp19
      to immobilized trimeric or tetrameric MBL. As shown by gel filtration, both MBL
      species formed 1:2 complexes with MASP-3 or MAp19. These results provide the
      first precise analysis of the major human MBL oligomers. The oligomerization
      state of MBL has a direct effect on its carbohydrate-binding properties, but no
      influence on the interaction with the MASPs.

PMID- 15728499
TI  - Hagfish leukocytes express a paired receptor family with a variable domain
      resembling those of antigen receptors.
AB  - Jawed vertebrates are equipped with TCR and BCR with the capacity to rearrange
      their V domains. By contrast, jawless vertebrates, represented by hagfish and
      lampreys, apparently lack such receptors. We describe in this study a family of
      hagfish genes carrying a single V-type domain resembling those of TCR/BCR. This
      multigene family, which we call agnathan paired receptors resembling Ag receptors
      (APAR), is expressed in leukocytes and predicted to encode a group of membrane
      glycoproteins with organizations characteristic of paired Ig-like receptors,
      consisting of activating and inhibitory forms. APAR has a J region in its V-type
      domain, and its V and J regions are encoded in a single exon. Thus, APAR is a
      member of the emerging families of diversified, innate immune-type receptors with
      TCR/BCR-like V-type domains and has many of the features expected for a
      primordial TCR/BCR-like receptor. The extracellular domain of APAR may be
      descended from a V-type domain postulated to have acquired recombination signal
      sequences in a jawed vertebrate lineage.

PMID- 15728498
TI  - Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping
      affinities and thermodynamics.
AB  - The NKG2x/CD94 family of C-type lectin-like immunoreceptors (x = A, B, C, E, and
      H) mediates surveillance of MHC class Ia cell surface expression, often
      dysregulated during infection or tumorigenesis, by recognizing the MHC class Ib
      protein HLA-E that specifically presents peptides derived from class Ia leader
      sequences. In this study, we determine the affinities and interaction
      thermodynamics between three NKG2x/CD94 receptors (NKG2A, NKG2C, and NKG2E) and
      complexes of HLA-E with four representative peptides. Inhibitory NKG2A/CD94 and
      activating NKG2E/CD94 receptors bind HLA-E with indistinguishable affinities, but
      with significantly higher affinities than the activating NKG2C/CD94 receptor.
      Despite minor sequence differences, the peptide presented by HLA-E significantly
      influenced the affinities; HLA-E allelic differences had no effect. These results
      reveal important constraints on the integration of opposing activating and
      inhibitory signals driving NK cell effector functions.

PMID- 15728500
TI  - Intracellular Salmonella inhibit antigen presentation by dendritic cells.
AB  - Dendritic cells (DC) are important APCs linking innate and adaptive immunity.
      During analysis of the intracellular activities of Salmonella enterica in DC, we
      observed that viable bacteria suppress Ag-dependent T cell proliferation. This
      effect was dependent on the induction of inducible NO synthase by DC and on the
      function of virulence genes in Salmonella pathogenicity island 2 (SPI2).
      Intracellular activities of Salmonella did not affect the viability, Ag uptake,
      or maturation of DC, but resulted in reduced presentation of antigenic peptides
      by MHC class II molecules. Increased resistance to reinfection was observed after
      vaccination of mice with SPI2-deficient Salmonella compared with mice vaccinated
      with SPI2-proficient Salmonella, and this correlated with an increased amount of
      CD4(+) as well as CD8(+) T cells. Our study is the first example of interference
      of an intracellular bacterial pathogen with Ag presentation by DC. The subversion
      of DC functions is a novel strategy deployed by this pathogen to escape immune
      defense, colonize host organs, and persist in the infected host.

PMID- 15728501
TI  - Loss of CD127 expression defines an expansion of effector CD8+ T cells in HIV
      infected individuals.
AB  - The immunodeficiency that follows HIV infection is related to the virus-mediated
      killing of infected CD4(+) T cells, the chronic activation of the immune system,
      and the impairment of T cell production. In this study we show that in HIV
      infected individuals the loss of IL-7R (CD127) expression defines the expansion
      of a subset of CD8(+) T cells, specific for HIV as well as other Ags, that show
      phenotypic (i.e., loss of CCR7 and CD62 ligand expression with enrichment in
      activated and/or proliferating cells) as well as functional (i.e., production of
      IFN-gamma, but not IL-2, decreased ex vivo proliferative potential and increased
      susceptibility to apoptosis) features of effector T cells. Importantly, in HIV
      infected individuals the levels of CD8(+)CD127(-) T cells are directly correlated
      with the main markers of disease progression (i.e., plasma viremia and CD4(+) T
      cell depletion) as well as with the indices of overall T cell activation. In all,
      these results identify the expansion of CD8(+)CD127(-) effector-like T cells as a
      novel feature of the HIV-associated immune perturbation. Further studies are thus
      warranted to determine whether measurements of CD127 expression on CD8(+) T cells
      may be useful in the clinical management of HIV-infected individuals.

PMID- 15728502
TI  - A crucial role for tryptophan catabolism at the host/Candida albicans interface.
AB  - By mediating tryptophan catabolism, the enzyme indoleamine 2,3-dioxygenase (IDO)
      has a complex role in immunoregulation in infection, pregnancy, autoimmunity,
      transplantation, and neoplasia. We hypothesized that IDO might affect the outcome
      of the infection in mice infected with Candida albicans by virtue of its potent
      regulatory effects on inflammatory and T cell responses. IDO expression was
      examined in mice challenged with the fungus along with the consequences of its
      blockade by in vivo treatment with an enzyme inhibitor. We found that IDO
      activity was induced at sites of infection as well as in dendritic cells and
      effector neutrophils via IFN-gamma- and CTLA-4-dependent mechanisms. IDO
      inhibition greatly exacerbated infection and associated inflammatory pathology as
      a result of deregulated innate and adaptive/regulatory immune responses. However,
      a role for tryptophan catabolism was also demonstrated in a fungus-autonomous
      fashion; its blockade in vitro promoted yeast-to-hyphal transition. These results
      provide novel mechanistic insights into complex events that, occurring at the
      fungus/pathogen interface, relate to the dynamics of host adaptation to the
      fungus. The production of IFN-gamma may be squarely placed at this interface,
      where IDO activation probably exerts a fine control over fungal morphology as
      well as inflammatory and adaptive antifungal responses.

PMID- 15728503
TI  - Development and migration of protective CD8+ T cells into the nervous system
      following ocular herpes simplex virus-1 infection.
AB  - After infection of epithelial surfaces, HSV-1 elicits a multifaceted antiviral
      response that controls the virus and limits it to latency in sensory ganglia.
      That response encompasses the CD8(+) T cells, whose precise role(s) is still
      being defined; immune surveillance in the ganglia and control of viral spread to
      the brain were proposed as the key roles. We tracked the kinetics of the CD8(+) T
      cell response across lymphoid and extralymphoid tissues after ocular infection.
      HSV-1-specific CD8(+) T cells first appeared in the draining (submandibular)
      lymph node on day 5 and were detectable in both nondraining lymphoid and
      extralymphoid tissues starting on day 6. However, although lymphoid organs
      contained both resting (CD43(low)CFSE(high)) and virus-specific cells at
      different stages of proliferation and activation, extralymphoid sites (eye,
      trigeminal ganglion, and brain) contained only activated cells that underwent
      more than eight proliferations (CD43(high)CFSE(neg)) and promptly secreted IFN
      gamma upon contact with viral Ags. Regardless of the state of activation, these
      cells appeared too late to prevent HSV-1 spread, which was seen in the eye (from
      day 1), trigeminal ganglia (from day 2), and brain (from day 3) well before the
      onset of a detectable CD8(+) T cell response. However, CD8(+) T cells were
      critical in reducing viral replication starting on day 6 and for its abrogation
      between days 8 and 10; CD8-deficient animals failed to control the virus,
      exhibited persisting high viral titers in the brain after day 6, and died of
      viral encephalitis between days 7 and 12. Thus, CD8(+) T cells do not control HSV
      1 spread from primary to tertiary tissues, but, rather, attack the virus in
      infected organs and control its replication in situ.

PMID- 15728504
TI  - The staphylococcal superantigen-like protein 7 binds IgA and complement C5 and
      inhibits IgA-Fc alpha RI binding and serum killing of bacteria.
AB  - The staphylococcal superantigen-like proteins (SSLs) are close relatives of the
      superantigens but are coded for by a separate gene cluster within a 19-kb region
      of the pathogenicity island SaPIn2. rSSL7 (formally known as SET1) bound with
      high affinity (K(D), 1.1 nM) to the monomeric form of human IgA1 and IgA2 plus
      serum IgA from primate, pig, rat, and horse. SSL7 also bound the secretory form
      of IgA found in milk from human, cow, and sheep, and inhibited IgA binding to
      cell surface FcalphaRI (CD89) and to a soluble form of the FcalphaRI protein. In
      addition to IgA, SSL7 bound complement factor C5 from human (K(D), 18 nM),
      primate, sheep, pig, and rabbit serum, and inhibited complement-mediated
      hemolysis and serum killing of a Gram-negative organism Escherichia coli. SSL7 is
      a superantigen-like protein secreted from Staphylococcus aureus that blocks IgA
      FcR interactions and inhibits complement, leading to increased survival of a
      sensitive bacterium in blood.

PMID- 15728505
TI  - Nonhealing infection despite Th1 polarization produced by a strain of Leishmania
      major in C57BL/6 mice.
AB  - Experimental Leishmania major infection in mice has been of immense interest
      because it was among the first models to demonstrate the importance of the
      Th1/Th2 balance to infection outcome in vivo. However, the Th2 polarization that
      promotes the development of nonhealing cutaneous lesions in BALB/c mice has
      failed to adequately explain the mechanisms underlying nonhealing forms of
      leishmaniasis in humans. We have studied a L. major strain from a patient with
      nonhealing lesions that also produces nonhealing lesions with ulcerations and
      high parasite burden in conventionally resistant C57BL/6 mice. Surprisingly,
      these mice develop a strong, polarized, and sustained Th1 response, as evidenced
      by high levels of IFN-gamma produced by Leishmania-specific cells in the draining
      lymph node and in the ear lesion, and an absence of IL-4 or IL-13. The parasites
      fail to be effectively cleared despite high level induction of inducible NO
      synthase in the lesion, and despite their sensitivity to killing by IFN-gamma
      activated macrophages in vitro. Infection of IL-10(-/-) mice, blockade of the IL
      10R, or depletion of CD25(+) cells during the chronic phase promotes parasite
      killing, indicating that IL-10 and regulatory T cells play a role in rendering
      the Th1 responses ineffective at controlling infection in the skin. Mice with
      nonhealing primary lesions are nonetheless resistant to reinfection in the other
      ear. We suggest that nonhealing infections in animal models that are explained
      not by aberrant Th2 development, but by overactivation of homeostatic pathways
      designed to control inflammation, provide better models to understand nonhealing
      or reactivation forms of leishmaniasis in humans.

PMID- 15728506
TI  - Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid
      dendritic cells, which activates gene transcription through MyD88.
AB  - Human TLR10 is an orphan member of the TLR family. Genomic studies indicate that
      TLR10 is in a locus that also contains TLR1 and TLR6, two receptors known to
      function as coreceptors for TLR2. We have shown that TLR10 was not only able to
      homodimerize but also heterodimerized with TLRs 1 and 2. In addition, unlike TLR1
      and TLR6, TLR10 was expressed in a highly restricted fashion as a highly N
      glycosylated protein, which we detected in B cell lines, B cells from peripheral
      blood, and plasmacytoid dendritic cells from tonsil. We were also able to detect
      TLR10 in a CD1a(+) DC subset derived from CD34(+) progenitor cells which resemble
      Langerhans cells in the epidermis. Although we were unable to identify a specific
      ligand for TLR10, by using a recombinant CD4TLR10 molecule we also demonstrated
      that TLR10 directly associates with MyD88, the common Toll IL-1 receptor domain
      adapter. Additionally, we have characterized regions in the Toll IL-1 receptor
      domain of TLR10 that are essential in the activation of promoters from certain
      inflammatory cytokines. Even though TLR10 expression has not been detected in
      mice, we have identified a partial genomic sequence of the TLR10 gene that was
      present but nonfunctional and disrupted by a retroviral insertion in all mouse
      strains tested. However, a complete TLR10 sequence could be detected in the rat
      genome, indicating that a functional copy may be preserved in this species.

PMID- 15728507
TI  - Breast milk-derived antigen-specific CD8+ T cells: an extralymphoid effector
      memory cell population in humans.
AB  - Although mouse studies have demonstrated the presence of an effector memory
      population in nonlymphoid tissues, the phenotype of human CD8(+) T cells present
      in such compartments has not been characterized. Because of the relatively large
      number of CD8(+) T cells present in breast milk, we were able to characterize the
      phenotype of this cell population in HIV-infected and uninfected lactating women.
      CMV, influenza virus, EBV, and HIV-specific CD8(+) T cells as measured by the IFN
      gamma ELISPOT and MHC class I tetramer staining were all present at greater
      frequencies in breast milk as compared with blood. Furthermore, a greater
      percentage of the breast milk CD8(+) T cells expressed the intestinal homing
      receptor, CD103, and the mucosal homing receptor CCR9. Breast milk T cells were
      predominantly CD45RO(+)HLADR(+) and expressed low levels of CD45RA, CD62L, and
      CCR7 consistent with an effector memory population. Conversely, T cells derived
      from blood were mainly characterized as central memory cells (CCR7(+)CD62L(+)).
      These results demonstrate a population of extralymphoid CD8(+) T cells with an
      effector memory phenotype in humans, which could contribute to enhanced local
      virologic control and the relative lack of HIV transmission via this route.

PMID- 15728508
TI  - CD4+CD25+ regulatory T cells control innate immune reactivity after injury.
AB  - Major injury initiates a systemic inflammatory response that can be detrimental
      to the host. We have recently reported that burn injury primes innate immune
      cells for a progressive increase in TLR4 and TLR2 agonist-induced proinflammatory
      cytokine production and that this inflammatory phenotype is exaggerated in
      adaptive immune system-deficient (Rag1(-/-)) mice. The present study uses a
      series of adoptive transfer experiments to determine which adaptive immune cell
      type(s) has the capacity to control innate inflammatory responses after injury.
      We first compared the relative changes in TLR4- and TLR2-induced TNF-alpha, IL
      1beta, and IL-6 production by spleen cell populations prepared from wild-type
      (WT), Rag1(-/-), CD4(-/-), or CD8(-/-) mice 7 days after sham or burn injury. Our
      findings indicated that splenocytes prepared from burn-injured CD8(-/-) mice
      displayed TLR-induced cytokine production levels similar to those in WT mice. In
      contrast, spleen cells from burn-injured CD4(-/-) mice produced cytokines at
      significantly higher levels, equivalent to those in Rag1(-/-) mice. Moreover,
      reconstitution of Rag1(-/-) or CD4(-/-) mice with WT CD4(+) T cells reduced
      postinjury cytokine production to WT levels. Additional separation of CD4(+) T
      cells into CD4(+)CD25(+) and CD4(+)CD25(-) subpopulations before their adoptive
      transfer into Rag1(-/-) mice showed that CD4(+)CD25(+) T cells were capable of
      reducing TLR-stimulated cytokine production levels to WT levels, whereas
      CD4(+)CD25(-) T cells had no regulatory effect. These findings suggest a
      previously unsuspected role for CD4(+)CD25(+) T regulatory cells in controlling
      host inflammatory responses after injury.

PMID- 15728509
TI  - Pseudomonas aeruginosa lipopolysaccharide induction of keratinocyte
      proliferation, NF-kappa B, and cyclin D1 is inhibited by indomethacin.
AB  - NF-kappaB is activated during acute inflammatory states as well as in other
      injury response disease states. Several pathologic states in squamous tissue
      injury response are characterized by increased squamous proliferation. This study
      was performed to investigate the hypothesis that Pseudomonas aeruginosa LPS is
      able to activate a proliferative phenotype in squamous cells via NF-kappaB
      induction and that this NF-kappaB-mediated response may be abrogated with the
      classic anti-inflammatory agent indomethacin. EMSA, luciferase reporter gene
      experiments, Western blots, and cellular proliferation assays were performed in
      normal and transformed human keratinocytes after stimulation with P. aeruginosa
      LPS. EMSA and luciferase reporter gene assays showed a 3- to 5-fold induction of
      active NF-kappaB in human keratinocyte cell lines after stimulation with P.
      aeruginosa LPS. The stimulation correlated with significantly increased cellular
      proliferation. As one potential mechanism for this increase in proliferation, an
      NF-kappaB-specific activation of cyclin D1 was observed. Both the NF-kappaB
      induction and proliferation response were inhibited with indomethacin and in
      dominant negative stable transfection clones. P. aeruginosa LPS activates
      proliferation of human keratinocytes, potentially through the induction of NF
      kappaB and cyclin D1. These findings suggest that bacterial components can
      contribute to proliferative disease states in squamous epithelium through NF
      kappaB activation.

PMID- 15728510
TI  - The production of IL-1 receptor antagonist in IFN-beta-stimulated human monocytes
      depends on the activation of phosphatidylinositol 3-kinase but not of STAT1.
AB  - IFN-beta induces the production of secreted IL-1R antagonist (sIL-1Ra) without
      triggering synthesis of the agonist IL-1beta in human monocytes. This might
      account for its anti-inflammatory properties. Canonically, IFN-beta signals
      through activation of JAK/STAT pathway, although PI3K and MAPK have also been
      involved. In this study, the role of PI3K, MEK1, and STAT1 in IFN-beta-induced
      sIL-1Ra production is investigated in freshly isolated human blood monocytes.
      PI3K, but not MEK1 activation is essential for sIL-1Ra production in monocytes
      treated with IFN-beta, as demonstrated by using the respective inhibitors of PI3K
      and MEK1, Ly294002 and PD98059. The use of cycloheximide and actinomycin D shows
      that sIL-1Ra was an immediate early gene induced by IFN-beta and that PI3K was
      controlling sIL-1Ra gene transcription. Although both inhibitors of PI3K and MEK1
      diminished the Ser(727) phosphorylation of STAT1 induced by IFN-beta, only
      Ly294002 inhibited sIL-1Ra production. Furthermore, the inhibition of STAT1
      Ser(727) phosphorylation by Ly294002 did not affect STAT1 translocation,
      suggesting that STAT1 was not involved in sIL-1Ra gene induction. This was
      confirmed in monocytes that were transfected with small interfering RNA
      specifically targeting STAT1. Indeed, monocytes in which effective STAT1 gene
      knockdown was achieved were fully responsive to IFN-beta in terms of sIL-1Ra
      production. Taken together, the present data demonstrate that the induction of
      sIL-1Ra transcription and production by IFN-beta in human monocytes involved
      PI3K, but not STAT1 activation.

PMID- 15728511
TI  - Lysophosphatidylcholine modulates neutrophil oxidant production through elevation
      of cyclic AMP.
AB  - Lysophosphatidylcholine (LPC) is an oxidized phospholipid present in micromolar
      concentrations in blood and inflamed tissues. The effects of LPC on neutrophil
      functions remain incompletely understood, because conflicting reports exist for
      its stimulatory and inhibitory roles. We report in this study that LPC inhibits
      superoxide generation in fMLP- and PMA-stimulated neutrophils without affecting
      fMLP-induced Ca(2+) mobilization and cell viability. This effect was observed
      with LPC dissolved in ethanol, but not with LPC stock solutions prepared in water
      or in BSA-containing aqueous solution with sonication. Under the same
      experimental conditions, platelet-activating factor primed neutrophils for
      superoxide generation. The inhibitory effect of LPC was observed within 30 s
      after its application and was maximal at LPC concentrations between 0.1 and 1
      muM. Inhibition of superoxide generation was accompanied by a 2.5-fold increase
      in the intracellular cAMP concentration. In addition, LPC reduced fMLP-stimulated
      phosphorylation of ERK and Akt and membrane translocation of p67(phox) and
      p47(phox). The protein kinase A inhibitors H-89 and adenosine 3'5'-cyclic
      monophosphorothioate Rp-isomer (Rp-cAMP) partially restored superoxide production
      in LPC-treated neutrophils, indicating involvement of protein kinase A in LPC
      mediated inhibition. Using an ex vivo mouse lung perfusion model that measures
      lung weight change and capillary filtration coefficient, we found that LPC
      prevented lung vascular injury mediated by fMLP-activated neutrophils. Taken
      together, these results suggest that LPC-induced elevation of intracellular cAMP
      is partially responsible for its inhibition of neutrophil NADPH oxidase
      activation. A similar mechanism of inhibition may be used for the control of
      neutrophil-mediated tissue injury.

PMID- 15728513
TI  - B7RP-1 is not required for the generation of Th2 responses in a model of allergic
      airway inflammation but is essential for the induction of inhalation tolerance.
AB  - The recently described ICOS-B7RP-1 costimulatory pathway has been implicated in
      the generation of effector Th2 responses and, hence, has become an attractive
      therapeutic target for allergic diseases. In the present study, we used B7RP-1
      deficient mice to investigate the role of B7RP-1 in the generation and
      maintenance of Th2 responses in a model of mucosal allergic airway inflammation.
      We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context
      of GM-CSF leads to airway eosinophilic inflammation. This response was long
      lasting because rechallenge of mice with the same Ag recapitulated airway
      eosinophilia. Moreover, significant expression of T1/ST2 on T cells and
      production of Th2-affiliated cytokines (IL-5, IL-4, and IL-13) and Igs (IgE and
      IgG1) conclusively demonstrate the generation of a Th2 response in the absence of
      B7RP-1. In addition, expression of two major Th2-associated costimulatory
      molecules-CD28 and ICOS-indicates T cell activation in the absence of B7RP-1
      signaling. Finally, B7RP-1 knockout mice are resistant to the induction of
      inhalation tolerance as indicated by the sustained eosinophilia in the lung and
      IL-5 production. In summary, our results demonstrate that in a model of mucosal
      allergic sensitization, the ICOS-B7RP-1 pathway is redundant for the generation
      of Th2 responses but essential for the induction of inhalation tolerance.

PMID- 15728512
TI  - IL-10 gene-deficient mice lack TGF-beta/Smad signaling and fail to inhibit
      proinflammatory gene expression in intestinal epithelial cells after the
      colonization with colitogenic Enterococcus faecalis.
AB  - Nonpathogenic enteric bacterial species initiate and perpetuate experimental
      colitis in IL-10 gene-deficient mice (IL-10(-/-)). Bacteria-specific effects on
      the epithelium are difficult to dissect due to the complex nature of the gut
      microflora. We showed that IL-10(-/-) mice compared with wild-type mice fail to
      inhibit proinflammatory gene expression in native intestinal epithelial cells
      (IEC) after the colonization with colitogenic Gram-positive Enterococcus
      faecalis. Interestingly, proinflammatory gene expression was transient after 1 wk
      of E. faecalis monoassociation in IEC from wild-type mice, but persisted after 14
      wk of bacterial colonization in IL-10(-/-) mice. Accordingly, wild-type IEC
      expressed phosphorylated NF-kappaB subunit RelA (p65) and phosphorylated Smad2
      only at day 7 after bacterial colonization, whereas E. faecalis-monoassociated IL
      10(-/-) mice triggered persistent RelA, but no Smad2 phosphorylation in IEC at
      days 3, 7, 14, and 28. Consistent with the induction of TLR2-mediated RelA
      phosphorylation and proinflammatory gene expression in E. faecalis-stimulated
      cell lines, TLR2 protein expression was absent after day 7 from E. faecalis
      monoassociated wild-type mice, but persisted in IL-10(-/-) IEC. Of note, TGF
      beta1-activated Smad signaling was associated with the loss of TLR2 protein
      expression and the inhibition of NF-kappaB-dependent gene expression in IEC
      lines. In conclusion, E. faecalis-monoassociated IL-10(-/-), but not wild-type
      mice lack protective TGF-beta/Smad signaling and fail to inhibit TLR2-mediated
      proinflammatory gene expression in the intestinal epithelium, suggesting a
      critical role for IL-10 and TGF-beta in maintaining normal epithelial cell
      homeostasis in the interplay with commensal enteric bacteria.

PMID- 15728514
TI  - Identification of a peptide derived from vaccinia virus A52R protein that
      inhibits cytokine secretion in response to TLR-dependent signaling and reduces in
      vivo bacterial-induced inflammation.
AB  - TLRs recognize and respond to conserved motifs termed pathogen-associated
      molecular patterns. TLRs are characterized by an extracellular leucine-rich
      repeat motif and an intracellular Toll/IL-1R domain. Triggering of TLRs by
      pathogen-associated molecular patterns initiates a series of intracellular
      signaling events resulting in an inflammatory immune response designed to contain
      and eliminate the pathogen. Vaccinia virus encodes immunoregulatory proteins,
      such as A52R, that can effectively inhibit intracellular Toll/IL-1R signaling,
      resulting in a diminished host immune response and enhancing viral survival. In
      this study, we report the identification and characterization of a peptide
      derived from the A52R protein (sequence DIVKLTVYDCI) that, when linked to the
      nine-arginine cell transduction sequence, effectively inhibits cytokine secretion
      in response to TLR activation. The peptide had no effect on cytokine secretion
      resulting from cell activation that was initiated independent of TLR stimulation.
      Using a mouse model of otitis media with effusion, administration of heat
      inactivated Streptococcus pneumoniae into the middle ears of BALB/c mice resulted
      in a significant inflammatory response that was dramatically reduced with peptide
      treatment. The identification of this peptide that selectively targets TLR
      dependent signaling may have application in the treatment of chronic inflammation
      initiated by bacterial or viral infections.

PMID- 15728515
TI  - Enhanced apoptotic cell clearance capacity and B cell survival factor production
      by IL-10-activated macrophages: implications for Burkitt's lymphoma.
AB  - Burkitt's lymphoma (BL) is typified by frequent tumor cell apoptosis and
      significant macrophage infiltration. Since BL cells have an inherent tendency to
      undergo apoptosis at a high rate, we reasoned that macrophages in BL are
      functionally enhanced in at least two activities that have implications for tumor
      pathogenesis: 1) engulfment of apoptotic cells, an anti-inflammatory process
      known to suppress immune responses, and 2) production of BL cell survival factors
      that limit the extent of tumor cell apoptosis. In this study, we show that the
      microenvironment of BL is rich in the pleiotropic cytokine IL-10, which can be
      produced by both tumor cells and macrophages, and that IL-10-activated human
      macrophages have enhanced capacity to engulf apoptotic cells in vitro. This was
      found to be dependent on the macrophage tethering receptor of apoptotic cells,
      CD14. Furthermore, IL-10-activated macrophages were found to produce markedly
      higher levels of the B cell survival factor, B cell-activating factor of the TNF
      family/B lymphocyte stimulator (BAFF/BLyS) than macrophages matured in the
      absence of IL-10. Coculture of macrophages with BL cells further enhanced BAFF
      secretion. Significantly, we show that enhancement of BL cell survival by IL-10
      activated macrophages is mediated by a BAFF-dependent component and that BAFF is
      produced at high levels by tumor-associated macrophages in situ. These results
      indicate that macrophages, regulated by IL-10, have the potential to promote BL
      pathogenesis, first, through suppression of antitumor immunity following enhanced
      engulfment of apoptotic tumor cells and, second, through increased production of
      tumor cell growth/survival factors.

PMID- 15728516
TI  - Suppressors of cytokine signaling-1 and -3 regulate osteoclastogenesis in the
      presence of inflammatory cytokines.
AB  - Bone metabolism and the immune system have a correlative relationship, and both
      are controlled by various common cytokines, such as IFNs and ILs, produced in the
      bone microenvironments. The suppressor of cytokine signaling-1 (SOCS1) and SOCS3
      are negative regulators of such cytokines. Although SOCSs are shown to be induced
      during osteoclast differentiation, their physiological roles in osteoclast
      differentiation and function have not been clarified. Thus, we examined the roles
      of SOCS1 and SOCS3 in osteoclastogenesis using SOCS1- and SOCS3-deficient mice.
      IFN-gamma-mediated inhibition of osteoclast differentiation from bone marrow
      derived monocytes (BMMs) was strongly enhanced in SOCS1-deficient BMMs, but was
      diminished in SOCS1-overexpressing BMMs. Moreover, LPS-induced osteoclastogenesis
      and bone destruction in vivo were suppressed in SOCS1(+/-) mice compared with
      those in wild-type mice, suggesting that SOCS1 antagonizes the inhibitory effect
      of IFN-gamma on osteoclastogenesis. SOCS3 did not alter the inhibitory effect of
      IFNs in osteoclastogenesis in both gain and loss of functional assays; however,
      the suppressive effect of IL-6 on osteoclast differentiation was greater in SOCS3
      deficient BMMs than in wild-type BMMs in vitro. In addition, IL-6 significantly
      prevented LPS-induced bone destruction in SOCS3-deficient mice, although it
      failed in wild-type mice in vivo. In SOCS3-deficient BMMs, expression levels of
      TNF-receptor-associated factor-6 and IkappaB were drastically reduced and
      receptor activator of the NF-kappaB ligand-induced IkappaB phosphorylation was
      severely impaired in the presence of IL-6. These data suggest that both SOCS1 and
      SOCS3 regulate osteoclastogenesis by blocking the inhibitory effect of
      inflammatory cytokines on receptor activator of the NF-kappaB ligand-mediated
      osteoclast differentiation signals. Selective suppression of SOCS1 and SOCS3 in
      osteoclast precursors may be a possible therapeutic strategy for inflammatory
      bone destruction.

PMID- 15728517
TI  - Tumor cells deactivate human monocytes by up-regulating IL-1 receptor associated
      kinase-M expression via CD44 and TLR4.
AB  - Although blood monocytes possess significant cytotoxic activity against tumor
      cells, tumor-infiltrating monocytes are commonly deactivated in cancer patients.
      Monocytes pre-exposed to tumor cells show significantly decreased expression
      levels of TNF-alpha, IL-12p40, and IL-1R-associated kinase (IRAK)-1. Activation
      of the Ser/Thr kinase IRAK-1 is an important event in several inflammatory
      processes. By contrast, another IRAK family member, IRAK-M, negatively regulates
      this pathway, and is up-regulated in cultures of endotoxin-tolerant monocytes and
      in monocytes from septic patients within the timeframe of tolerance. In this
      study, we show that IRAK-M expression is enhanced at the mRNA and protein level
      in human monocytes cultured in the presence of tumor cells. IRAK-M was induced in
      monocytes upon coculturing with different tumor cells, as well as by fixed tumor
      cells and medium supplemented with the supernatant from tumor cell cultures.
      Moreover, blood monocytes from patients with chronic myeloid leukemia and
      patients with metastasis also overexpressed IRAK-M. Low concentrations of
      hyaluronan, a cell surface glycosaminoglycan released by tumor cells, also up
      regulated IRAK-M. The induction of IRAK-M by hyaluronan and tumor cells was
      abolished by incubation with anti-CD44 or anti-TLR4 blocking Abs. Furthermore,
      down-regulation of IRAK-M expression by small interfering RNAs specific for IRAK
      M reinstates both TNF-alpha mRNA expression and protein production in human
      monocytes re-exposed to a tumor cell line. Altogether, our findings indicate that
      deactivation of human monocytes in the presence of tumor cells involves IRAK-M up
      regulation, and this effect appears to be mediated by hyaluronan through the
      engagement of CD44 and TLR4.

PMID- 15728518
TI  - Macrophages induce the inflammatory response in the pulmonary Arthus reaction
      through G alpha i2 activation that controls C5aR and Fc receptor cooperation.
AB  - Complement and FcgammaR effector pathways are central triggers of immune
      inflammation; however, the exact mechanisms for their cooperation with effector
      cells and their nature remain elusive. In this study we show that in the lung
      Arthus reaction, the initial contact between immune complexes and alveolar
      macrophages (AM) results in plasma complement-independent C5a production that
      causes decreased levels of inhibitory FcgammaRIIB, increased levels of activating
      FcgammaRIII, and highly induced FcgammaR-mediated TNF-alpha and CXCR2 ligand
      production. Blockade of C5aR completely reversed such changes. Strikingly,
      studies of pertussis toxin inhibition show the essential role of G(i)-type G
      protein signaling in C5aR-mediated control of the regulatory FcgammaR system in
      vitro, and analysis of the various C5aR-, FcgammaR-, and G(i)-deficient mice
      verifies the importance of Galpha(i2)-associated C5aR and the FcgammaRIII
      FcgammaRIIB receptor pair in lung inflammation in vivo. Moreover, adoptive
      transfer experiments of C5aR- and FcgammaRIII-positive cells into C5aR- and
      FcgammaRIII-deficient mice establish AM as responsible effector cells. AM lacking
      either C5aR or FcgammaRIII do not possess any such inducibility of immune complex
      disease, whereas reconstitution with FcgammaRIIB-negative AM results in an
      enhanced pathology. These data suggest that AM function as a cellular link of C5a
      production and C5aR activation that uses a Galpha(i2)-dependent signal for
      modulating the two opposing FcgammaR, FcgammaRIIB and FcgammaRIII, in the
      initiation of the inflammatory cascade in the lung Arthus reaction.

PMID- 15728519
TI  - Alloreactive memory T cells are responsible for the persistence of graft-versus
      host disease.
AB  - Graft-vs-host disease (GVHD) is caused by a donor T cell anti-host reaction that
      evolves over several weeks to months, suggesting a requirement for persistent
      alloreactive T cells. Using the C3H.SW anti-C57BL/6 (B6) mouse model of human
      GVHD directed against minor histocompatibility Ags, we found that donor CD8(+) T
      cells secreting high levels of IFN-gamma in GVHD B6 mice receiving C3H.SW naive
      CD8(+) T cells peaked by day 14, declined by day 28 after transplantation, and
      persisted thereafter, corresponding to the kinetics of a memory T cell response.
      Donor CD8(+) T cells recovered on day 42 after allogeneic bone marrow
      transplantation expressed the phenotype of CD44(high)CD122(high)CD25(low), were
      able to homeostatically survive in response to IL-2, IL-7, and IL-15 and rapidly
      proliferated upon restimulation with host dendritic cells. Both allogeneic
      effector memory (CD44(high)CD62L(low)) and central memory (CD44(high)CD62L(high))
      CD8(+) T cells were identified in B6 mice with ongoing GVHD, with effector memory
      CD8(+) T cells as the dominant (>80%) population. Administration of these
      allogeneic memory CD8(+) T cells into secondary B6 recipients caused virulent
      GVHD. A similar allogeneic memory CD4(+) T cell population with the ability to
      mediate persistent GVHD was also identified in BALB/b mice receiving minor
      histocompatibility Ag-mismatched B6 T cell-replete bone marrow transplantation.
      These results indicate that allogeneic memory T cells are generated in vivo
      during GVH reactions and are able to cause GVHD, resulting in persistent host
      tissue injury. Thus, in vivo blockade of both alloreactive effector and memory T
      cell-mediated host tissue injury may prove to be valuable for GVHD prevention and
      treatment.

PMID- 15728520
TI  - Processing of C3b-opsonized immune complexes bound to non-complement receptor 1
      (CR1) sites on red cells: phagocytosis, transfer, and associations with CR1.
AB  - Severe anemia is a lethal complication of Plasmodium falciparum malaria,
      particularly in children. Recent studies in children with severe P. falciparum
      anemia have demonstrated elevated levels of E-bound Abs, reduced E-associated
      complement receptor 1 (CR1) and decay-accelerating factor (DAF), and pronounced
      splenic enlargement, suggesting a mechanism for E loss involving Abs, complement,
      and phagocytosis. Motivated by these reports, we have developed an in vitro model
      in which human E with Abs and complement bound to CR1, DAF, or glycophorin A are
      incubated with model human macrophages (the THP-1 cell line). Previous work has
      demonstrated that immune complex (IC) substrates bound to E CR1, either by an Ab
      or via C3b, are transferred to macrophages with loss of CR1. In this study, we
      report that IC bound to DAF or glycophorin A by an Ab linkage are also
      transferred to macrophages. DAF is lost from the E during the transfer of DAF
      bound IC, but the transfer of CR1-bound IC does not lead to a significant loss of
      DAF. Using glycophorin A-bound IC, we observe competition between transfer of IC
      and phagocytosis of the E: a fraction (</=15%) of the E was phagocytosed, while
      the remaining E were stripped of IC. We also examined the organization of CR1 and
      DAF in the presence of E-bound Ab/complement. We find that CR1, but not DAF,
      colocalizes with IgM mAb-C3b and IC-C3b substrates attached to glycophorin A. We
      observe that the binding of the IgM mAb-C3b to glycophorin A induces a novel
      unclustering of CR1.

PMID- 15728522
TI  - Induction by IL-1 beta of tissue inhibitor of metalloproteinase-1 in human
      orbital fibroblasts: modulation of gene promoter activity by IL-4 and IFN-gamma.
AB  - Thyroid-associated ophthalmopathy (TAO), an autoimmune component of Graves'
      disease, is associated with profound connective tissue remodeling and fibrosis
      that appear to involve the selective activation of orbital fibroblasts.
      Accumulation of extracellular matrix molecules is a hallmark of this process.
      Here we report that orbital fibroblasts treated with IL-1beta express high levels
      of tissue inhibitor of metalloproteinase-1 (TIMP-1), an important modulator of
      matrix metalloproteinase activity. These high levels are associated with
      increased TIMP-1 activity. The induction is mediated at the pretranslational
      level and involves activating the TIMP-1 gene promoter. IL-1beta activates the
      ERK 1/2 pathway in these fibroblasts and interrupting this signaling either with
      PD98059, a chemical inhibitor of MEK, or by transfecting cells with a dominant
      negative ERK 1 plasmid results in the attenuation of TIMP-1 induction.
      Surprisingly, treatment with IL-4 or IFN-gamma could also block the IL-1beta
      induction by attenuating TIMP-1 gene promoter activity. These findings suggest
      that TIMP-1 expression in orbital fibroblasts following activation with IL-1beta
      could represent an important therapeutic target for modifying the proteolytic
      environment. This might alter the natural course of tissue remodeling in TAO.

PMID- 15728521
TI  - Increased blood myeloid dendritic cells and dendritic cell-poietins in Langerhans
      cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a
      reactive proliferative disease of unknown pathogenesis. Current therapies are
      based on nonspecific immunosuppression. Because multiple APCs, including
      Langerhans cells and macrophages, are involved in the lesion formation, we
      surmised that LCH is a disease of myeloid blood precursors. We found that lin(-)
      HLA-DR(+)CD11c-+ precursors of dendritic cells, able to give rise to either
      Langerhans cells or macrophages, are significantly (p = 0.004) increased in the
      blood of LCH patients. The analysis of serum cytokines in 24 patients
      demonstrated significantly elevated levels of hemopoietic cytokines such as fms
      like tyrosine kinase ligand (FLT3-L, a dendritic cell-mobilizing factor,
      approximately 2-fold) and M-CSF ( approximately 4-fold). Higher levels of these
      cytokines correlated with patients having more extensive disease. Serum levels of
      FLT3-L and M-CSF were highest in high risk patients with extensive skin and/or
      multisystem involvement. Finally, patients with bone lesions had relatively
      higher levels of M-CSF and of stem cell factor. Thus, early hemopoietic cytokines
      such as FLT3-L, stem cell factor, and M-CSF maybe relevant in LCH pathogenesis
      and might be considered as novel therapeutic targets.

PMID- 15728524
TI  - Generation of an optimized polyvalent monocyte-derived dendritic cell vaccine by
      transfecting defined RNAs after rather than before maturation.
AB  - Transfection with RNA is an attractive method of Ag delivery to dendritic cells
      (DCs), but has not yet been standardized. We describe in this study the methods
      to efficiently generate an optimized mature monocyte-derived DC vaccine at
      clinical scale based on the electroporation of several RNAs either into immature
      DC followed by maturation or, alternatively, directly into mature DCs, which has
      not been possible so far with such high efficiency. Electroporation of DCs
      resulted in high yield, high transfection efficiency (>90%), and high migration
      capacity. Intracellular staining allowed the study of the expression kinetics of
      Ags encoded by the transfected RNAs (MelanA, MAGE-3, and survivin) and a
      validation of the vaccine (>/=90% transfection efficiency). Expression of all
      three Ags peaked 3-4 h after electroporation in DC transfected either before or
      after maturation, but decreased differently. The DC vaccine can also be
      cryopreserved and nevertheless retains its viability, stimulatory capacity as
      well as migratory activity. In addition, we uncover that DC transfected after
      rather than before maturation appear to be preferable vaccines not only from a
      production point of view but also because they appear to be immunologically
      superior for CTL induction in sharp contrast to common belief. DCs transfected
      after maturation not only more effectively generate and present the Mage-3.A1 and
      MelanA.A2.1 epitopes to T cell clones, but they even are superior in priming to
      the standard proteasome-dependent MelanA.A2.1 wild-type prototype tumor epitope,
      both in terms of T cell expansion and effector function on a per cell basis.

PMID- 15728523
TI  - MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined
      with granulocyte-macrophage colony-stimulating factor and montanide ISA-51
      adjuvant and administered as part of a multipeptide vaccine for melanoma.
AB  - Twelve peptides derived from melanocyte differentiation proteins and cancer
      testis Ags were combined and administered in a single mixture to patients with
      resected stage IIB, III, or IV melanoma. Five of the 12 peptides included in this
      mixture had not previously been evaluated for their immunogenicity in vivo
      following vaccination. We report in this study that at least three of these five
      peptides (MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622)) are immunogenic
      when administered with GM-CSF in Montanide ISA-51 adjuvant. T cells secreting IFN
      gamma in response to peptide-pulsed target cells were detected in peripheral
      blood and in the sentinel immunized node, the node draining a vaccine site, after
      three weekly injections. The magnitude of response typically reached a maximum
      after two vaccines, and though sometimes diminished thereafter, those responses
      typically were still detectable 6 wks after the last vaccines. Most importantly,
      tumor cell lines expressing the appropriate HLA-A restriction element and MAGE
      A1, MAGE-A10, or gp100 proteins were lysed by corresponding CTL. This report
      supports the continued use of the MAGE-A1(96-104), MAGE-A10(254-262), and
      gp100(614-622) epitopes in peptide-based melanoma vaccines and thus expands the
      list of immunogenic peptide Ags available for human use. Cancer-testis Ags are
      expressed in multiple types of cancer; thus the MAGE-A1(96-104) and MAGE-A10(254
      262) peptides may be considered for inclusion in vaccines against cancers of
      other histologic types, in addition to melanoma.

PMID- 15728525
TI  - Effect of human cytomegalovirus on expression of MHC class I-related chains A.
AB  - The MHC-encoded MHC class I-related chains A (MICA) glycoproteins are known to
      enhance the functions of NK and T cells by ligating the stimulating receptor
      NKG2D and appear to play an important role in host defense. Human CMV (HCMV)
      evades the immune response in many different ways, but has not previously been
      found to down-regulate MICA. We have found that a common form of MICA, which has
      a nucleotide insertion in exon 5 corresponding to the transmembrane region and no
      cytoplasmic tail, was increased on the surface of fibroblasts HFS-13 compared
      with the mock-infected sample of the same cells that had been cultured to
      confluence. However, an astrocytoma cell line, U373, which has a full-length
      variant of MICA, showed that the expression of MICA was decreased after HCMV
      infection. Retroviral transduction of different MICA alleles into fibroblasts HFF
      D, which express no MICA of their own, established that full-length MICA was down
      regulated by HCMV, and the truncated form was not. Fibroblasts with decreased
      MICA due to HCMV infection were found to be protected from NK cell killing,
      whereas in the presence of the truncated form of MICA, the virus-infected cells
      were destroyed. Thus, the truncated form of MICA, which is the most common, has a
      mutation that allows it to persist on the surface and hinder efforts of the virus
      to evade the immune response.

PMID- 15728527
TI  - H2A- and H2E-derived CD4+CD25+ regulatory T cells: a potential role in reciprocal
      inhibition by class II genes in autoimmune thyroiditis.
AB  - We recently described a novel H2E class II-transgenic model (A(-)E(+)) of
      experimental autoimmune thyroiditis (EAT) that permits disease induction with
      heterologous thyroglobulin (Tg), but unlike conventional susceptible strains,
      precludes self-reactivity to autologous mouse Tg. In transgenic E(+)B10
      (A(+)E(+)) mice, the presence of endogenous H2A genes is protective against H2E
      mediated thyroiditis, inhibiting EAT development. The suppressive effect of H2A
      genes on H2E-mediated thyroiditis mirrors previous reports of H2E suppression on
      H2A-mediated autoimmune diseases, including EAT. The mechanism of the reciprocal
      suppressive effect between class II genes is unclear, although the involvement of
      regulatory T cells has been proposed. We have recently reported that
      CD4(+)CD25(+) regulatory T cells mediate peripheral tolerance induced with mouse
      Tg in CBA mice. To determine whether these cells play a role in our E(+)
      transgenic model, we first confirmed the existence of CD4(+)CD25(+) T cells
      regulating thyroiditis in E(+)B10.Ab(0) (A(-)E(+)) and B10 (A(+)E(-)) mice by
      i.v. administration of CD25 mAb before EAT induction. The depletion of
      CD4(+)CD25(+) T cells enhanced thyroiditis induction in the context of either H2E
      or H2A. Moreover, reconstitution of CD4(+)CD25(+) T cells from naive B10 mice
      restored resistance to EAT. E(+)B10 (A(+)E(+)) mice were also depleted of
      CD4(+)CD25(+) T cells before the challenge to determine their role in thyroiditis
      in the presence of both H2A and H2E genes. Depletion of CD4(+)CD25(+) regulatory
      T cells offset the suppression of H2E-mediated thyroiditis by H2A. Thus, these
      regulatory T cells may be involved in the reciprocal-suppressive effect between
      class II genes.

PMID- 15728526
TI  - Thyroxine-binding antibodies inhibit T cell recognition of a pathogenic
      thyroglobulin epitope.
AB  - Thyroid hormone-binding (THB) Abs are frequently detected in autoimmune thyroid
      disorders but it is unknown whether they can exert immunoregulatory effects. We
      report that a THB mAb recognizing the 5' iodine atom of the outer phenolic ring
      of thyroxine (T4) can block T cell recognition of the pathogenic thyroglobulin
      (Tg) peptide (2549-2560) that contains T4 at aa position 2553 (T4(2553)).
      Following peptide binding to the MHC groove, the THB mAb inhibited activation of
      the A(k)-restricted, T4(2553)-specific, mouse T cell hybridoma clone 3.47, which
      does not recognize other T4-containing epitopes or noniodinated peptide
      analogues. Addition of the same THB mAb to T4(2553)-pulsed splenocytes largely
      inhibited specific activation of T4(2553)-primed lymph node cells and
      significantly reduced their capacity to adoptively transfer thyroiditis to naive
      CBA/J mice. These data demonstrate that some THB Abs can block recognition of
      iodine-containing Tg epitopes by autoaggressive T cells and support the view that
      such Abs may influence the development or maintenance of thyroid disease.

PMID- 15728528
TI  - ICOS-B7 homologous protein interactions are necessary for mercury-induced
      autoimmunity.
AB  - After exposure to subtoxic doses of heavy metals such as mercury, H-2(s) mice
      develop an autoimmune syndrome consisting of the rapid production of IgG
      autoantibodies that are highly specific for nucleolar autoantigens and a
      polyclonal increase in serum IgG1 and IgE. In this study, we explore the role of
      one of the members of the CD28-B7 costimulation families, ICOS-B7 homologous
      protein (B7h), in the regulation of mercury-induced autoimmunity. The expression
      of ICOS on T cells was more enhanced in susceptible A.SW mice than in non
      responsive C57BL/6 and DBA/2 mice after HgCl(2) treatment. Furthermore, in A.SW
      mice treated with HgCl(2), administration of a blocking anti-ICOS Ab effectively
      inhibited anti-nucleolar autoantibodies and total serum IgE production. Taken
      together, these results indicate that the ICOS-B7h costimulation pathway is
      required for this autoimmune syndrome and suggest that targeting this pathway
      might have therapeutic benefits for human autoimmune diseases.

PMID- 15728530
TI  - Effect of UV-A and UV-B irradiation on the metabolic profile of aqueous humor in
      rabbits analyzed by 1H NMR spectroscopy.
AB  - PURPOSE: This study was conducted to investigate metabolic changes in aqueous
      humor from rabbit eyes exposed to either UV-A or -B radiation, by using (1)H
      nuclear magnetic resonance (NMR) spectroscopy and unsupervised pattern
      recognition METHODS: methods. Both eyes of adult albino rabbits were irradiated
      with UV-A (366 nm, 0.589 J/cm(2)) or UV-B (312 nm, 1.667 J/cm(2)) radiation for 8
      minutes, once a day for 5 days. Three days after the last irradiation, samples of
      aqueous humor were aspirated, and the metabolic profiles analyzed with (1)H NMR
      spectroscopy. The metabolic concentrations in the exposed and control materials
      were statistically analyzed and compared, with multivariate methods and one-way
      ANOVA. RESULTS: UV-B radiation caused statistically significant alterations of
      betaine, glucose, ascorbate, valine, isoleucine, and formate in the rabbit
      aqueous humor. By using principal component analysis, the UV-B-irradiated samples
      were clearly separated from the UV-A-irradiated samples and the control group. No
      significant metabolic changes were detected in UV-A-irradiated samples.
      CONCLUSIONS: This study demonstrates the potential of using unsupervised pattern
      recognition methods to extract valuable metabolic information from complex (1)H
      NMR spectra. UV-B irradiation of rabbit eyes led to significant metabolic changes
      in the aqueous humor detected 3 days after the last exposure.

PMID- 15728529
TI  - Declines in arrestin and rhodopsin in the macula with progression of age-related
      macular degeneration.
AB  - PURPOSE: Biochemical analysis of age-related macular degeneration (AMD) at
      distinct stages of the disease will help further understanding of the molecular
      events associated with disease progression. This study was conducted to determine
      the ability of a new grading system for eye bank eyes, the Minnesota Grading
      System (MGS), to discern distinct stages of AMD so that retinal region-specific
      changes in rod photoreceptor protein expression from donors could be determined.
      METHODS: Donor eyes were assigned to a specific level of AMD by using the MGS.
      Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated
      by Western immunoblot analysis in the macular and peripheral regions of the
      neurosensory retina from donors at different stages of AMD. RESULTS: A
      significant linear decline in both arrestin and rhodopsin content correlated with
      progressive MGS levels in the macula. In contrast, the peripheral region showed
      no significant correlation between MGS level and the content of either protein.
      CONCLUSIONS: The statistically significant relationship between decreasing
      macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates
      the utility of the clinically based MGS to correspond with specific protein
      changes found at known, progressive stages of degeneration. Future biochemical
      analysis of clinically characterized donor eyes will further understanding of the
      pathobiochemistry of AMD.

PMID- 15728531
TI  - Cyclosporin a inhibits calcineurin/nuclear factor of activated T-cells signaling
      and induces apoptosis in retinoblastoma cells.
AB  - PURPOSE: Although the clinical efficacy of cyclosporin A (CSA) in retinoblastoma
      (RB) has been attributed to multidrug resistance reversal activity, the authors
      hypothesized that CSA is also directly toxic to RB cells through inhibition of
      calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling. METHODS:
      Antiproliferative effects of CSA, PSC-833 (a CSA analogue that does not inhibit
      CN), and FK506 (a CN inhibitor structurally unrelated to CSA) were evaluated in
      Y79 and Weri-RB1 cells by WST-1 assay. Apoptosis induction by CSA and PSC-833 was
      measured by detection of caspase 3/7 activity and by flow cytometry, using
      annexin-V and 7-AAD stains. Expression of CN was assayed in RB cells by
      immunocytochemistry. Expression of NFAT, a CN-dependent transcription factor
      family, and FK506 binding protein 12/12.6 (FKBP12/12.6), effectors of CN
      inhibition by FK506, was assayed in RB cells by Western blot analysis. NFAT
      activity was assayed in CSA-treated and -untreated Y79 cells transfected with an
      NFAT-sensitive reporter gene. RESULTS: CSA induced dose-dependent
      antiproliferative and proapoptotic effects at clinically achievable levels in Y79
      and Weri-RB1 cells. PSC-833 induced antiproliferative effects only at
      nonphysiologic concentrations with minimal associated apoptosis. FK506 induced
      minimal antiproliferative effects in RB cell lines, probably due to trace or
      absent FKBP12/12.6 expression. RB cell lines expressed CN-alpha, CN-beta, NFATc1,
      and NFATc3. CSA treatment also potently inhibited NFAT-mediated reporter gene
      transcription. CONCLUSIONS: These results demonstrate functional integrity of the
      CN/NFAT signaling cascade in RB cells and suggest that CSA is cytotoxic to RB
      cells through inhibition of this pathway and consequent apoptosis induction.

PMID- 15728532
TI  - Deleted in polyposis 1-like 1 gene (Dp1l1): a novel gene richly expressed in
      retinal ganglion cells.
AB  - PURPOSE: To characterize a novel gene, deleted in polyposis 1-like 1 (Dp1l1),
      which is expressed in the retina. METHODS: A systematic screening by subtraction
      hybridization of the cDNAs from mouse retina and mouse brain was performed to
      obtain novel genes expressed in the retina. In situ hybridization,
      immunohistochemistry, and intracellular localization analyses were performed to
      investigate the expression patterns of Dp1l1. The chromosomal location of Dp1l1
      was determined by radiation hybrid mapping. Bioinformatics was used for homology
      analysis. RESULTS: A novel gene, Dp1l1, was expressed abundantly in the retina.
      It encodes a 201-amino-acid protein, and the encoded protein is designated mouse
      TB2-like 1. It is highly homologous to the mouse TB2, which is encoded by deleted
      in polyposis 1 (Dp1). In situ hybridization and immunohistochemical analyses
      showed that Dp1l1 mRNA and the TB2-like 1 were localized richly in retinal
      ganglion cells (RGCs). TB2-like 1 was present in the cytoplasm in a punctate
      pattern. Dp1l1 was mapped to mouse chromosome 10 by radiation hybrid mapping.
      CONCLUSIONS: TB2-like 1 is a membrane protein that belongs to the
      YOP1/TB2/DP1/HVA22 family, and it probably plays an important role in
      intracellular membrane trafficking in RGCs, based on the properties of other
      homologous proteins.

PMID- 15728533
TI  - Protection of human conjunctival fibroblasts from NO-induced apoptosis by
      interleukin-4 or interleukin-13.
AB  - PURPOSE: To examine the possible roles of T helper type 2 (Th2) cell-derived
      cytokines in formation of the giant papillae characteristic in individuals with
      vernal keratoconjunctivitis, the effects of these cytokines on the proliferation
      and apoptosis of cultured human conjunctival fibroblasts were investigated.
      METHODS: Apoptosis was induced by the NO donor sodium nitroprusside. Cell
      viability was determined by measurement of mitochondrial metabolic activity, and
      apoptotic cells were identified on the basis either of nuclear morphology after
      staining with 4',6-diamidino-2-phenylindole or of TUNEL staining. The activation
      of antiapoptotic signaling mediated by the protein kinase Akt was assessed by
      immunoblot analysis and by an in vitro kinase assay. Expression of interleukin
      (IL)-4 and IL-13 receptor subunits was examined by reverse transcription and
      polymerase chain reaction analysis and by flow cytometry. RESULTS: IL-4 and IL
      13, but not IL-5, IL-9, or IL-10, induced the proliferation of conjunctival
      fibroblasts as well as protecting these cells from NO-induced apoptosis. Both IL
      4 and IL-13 induced the phosphorylation of Akt and increased the kinase activity
      of this enzyme in a manner that was sensitive to the phosphatidylinositol 3
      kinase inhibitors LY294002 or wortmannin. These inhibitors also blocked the
      antiapoptotic effects of IL-4 and IL-13. Transcripts encoding IL-4 and IL-13
      receptor components were detected in conjunctival fibroblasts, and the proteins
      were expressed at the cell surface. CONCLUSIONS: Among the various Th2 cytokines
      tested, only IL-4 and IL-13 induced the proliferation of human conjunctival
      fibroblasts and protected these cells from apoptosis. These effects may
      contribute to the formation of giant papillae in individuals with vernal
      keratoconjunctivitis.

PMID- 15728534
TI  - Survival of donor epithelial cells after limbal stem cell transplantation.
AB  - PURPOSE: To determine the long-term fate of donor epithelial cells after limbal
      allograft transplantation. METHODS: Corneal buttons and peripheral blood
      leukocytes were obtained at the time of penetrating keratoplasty from three
      patients who had undergone a successful limbal allograft transplantation.
      Microdissection was used to remove the corneal epithelial cells from the button.
      The presence of donor and recipient epithelial cells in each sample was
      determined by using PCR for DNA microsatellites. Phenotypic analysis of the
      epithelium was performed by immunohistochemistry. RESULTS: Various patterns of
      DNA microsatellites were observed. Nonrecipient cells (presumed to be donor) were
      consistently detected in all three corneal buttons. In two of the three cases,
      recipient cells were also detected, whereas in the third case, exclusively donor
      epithelial cells were found at 3.5 years after limbal allograft transplantation.
      Mild T-lymphocytes and macrophages were observed in one of the corneal buttons.
      CONCLUSIONS: This study provides evidence for the persistence of donor epithelial
      cells up to 3.5 years after limbal allograft transplantation and supports the use
      of systemic immunosuppressive therapy.

PMID- 15728535
TI  - Role of matrix metalloproteinase-9 in ex vivo expansion of human limbal
      epithelial cells cultured on human amniotic membrane.
AB  - PURPOSE: To investigate the expression and pivotal role of matrix
      metalloproteinase (MMP)-9 in the ex vivo expansion of human limbal explants with
      or without amniotic membrane (AM). METHODS: Corneoscleral buttons were cultured
      on intact, denuded AM or plastic dishes for 3 weeks. To determine the role of MMP
      9 in cell migration, either the MMP inhibitor GM6001 or an MMP-9 antibody was
      used. Expression of MMP-9 was determined by gelatin zymography, reverse
      transcription-polymerase chain reaction, and immunohistochemical staining.
      RESULTS: The expression of MMP-9 in all culture conditions increased in a time
      dependent manner. However, the active form of MMP-9 emerged only in cultures on
      both intact and denuded AM from the second week. The averaged corrected ratio of
      MMP-9 expression in cultures on intact AM versus those on denuded AM or plastic
      dishes was 2.76 +/- 0.69- or 4.25 +/- 0.30-fold, respectively, when total RNA was
      used as an internal control. MMP-9 transcripts were upregulated in cultures on
      intact AM compared with the other two culture conditions. Immunohistochemical
      staining demonstrated that the MMP-9 protein was located on the limbal epithelial
      cells. Upregulation of MMP-9 associated with cell migration was significantly
      attenuated by both GM6001 and MMP-9 antibody, consistent with the inhibition of
      MMP-9 activity, as determined by gelatin zymography. In contrast, the sizes of
      limbal outgrowth were not different between the control and MMP-9 antibody
      treated plastic dishes. CONCLUSIONS: These results demonstrated that MMP-9 not
      only was upregulated, it was also involved in the outgrowth of limbal epithelial
      cells. These results suggest that cell-cell matrix interaction is involved in the
      expansion of limbal epithelial cells on intact AM, and MMP-9 may be a key
      element.

PMID- 15728536
TI  - Animal compound-free medium and poloxamer for human corneal organ culture and
      deswelling.
AB  - PURPOSE: Eliminating fetal calf serum (FCS) from corneal organ culture (OC) media
      has long been a challenge. This study was an assessment of a new animal compound
      free (ACF) medium for corneal storage and of its combination with poloxamer for
      end-of-storage corneal deswelling. METHODS: A randomized controlled study with
      masked assessment compared the ACF medium to standard commercialized media
      containing 2% FCS and their combination with dextran for deswelling. Paired human
      corneas were randomly allocated at procurement, one to the ACF medium and the
      other to the FCS media, and then assessed at day (D)2 and D30 of OC storage and
      after 48 hours of deswelling. Comparison criteria were endothelial cell density
      (ECD) and morphometry by a corneal analyser, quality of endothelial visualization
      (using saline), EC mortality (trypan blue), corneal thickness, corneal
      transparency, and folding. Fifty-six corneas (28 pairs) with ECD of 2000
      cells/mm(2) or more were enrolled. Data were compared using paired tests with P <
      0.01 deemed significant. RESULTS: Parameters were similar at baseline (D2)
      between groups. Daily EC loss during the 30 days of storage was reduced with the
      ACF compared with standard (-0.31% +/- 0.30% vs. -0.88% +/- 0.38%, P < 0.001).
      With poloxamer 188 (Lutrol F68; BASF, Ludwigshafen, Germany), EC loss was
      substantially reduced (-1.43% +/- 3.60 vs. -15.41% +/- 10.13%, P < 0.001) and
      morphometry better preserved, despite thickness reduction, transparency
      improvement and folding reduction comparable to dextran. After 30 days of storage
      in ACF medium and deswelling in poloxamer 188, ECD was 30% higher (2466 +/- 447
      cells/mm(2) vs. 1729 +/- 281 cells/mm(2), P < 0.001). ACF medium alone and
      combined with poloxamer 188 considerably facilitated EC visualization at D30 and
      after deswelling. CONCLUSIONS: The ACF medium combined with poloxamer 188 for
      deswelling showed superiority over standard FCS medium in its ability to preserve
      EC viability and facilitate endothelial visualization. This innovative use of
      poloxamer for deswelling appears far less toxic than does dextran.

PMID- 15728538
TI  - Sensitizing effect of substance P on corneal epithelial migration induced by IGF
      1, fibronectin, or interleukin-6.
AB  - PURPOSE: Substance P (SP) is present in the sensory nerve fibers of the corneal
      epithelium. Various biological agents, including epidermal growth factor,
      fibronectin, interleukin-6, and the combination of SP and insulin-like growth
      factor (IGF)-1, promote the healing of corneal epithelial wounds. The role of SP
      in corneal epithelial migration was examined. METHODS: The effects of various
      agents on corneal epithelial migration were investigated with the rabbit cornea
      in an organ culture system. RESULTS: An SP-derived tetrapeptide, FGLM-amide,
      shifted the dose-response relations for the induction of corneal epithelial
      migration not only by an IGF-1-derived peptide (C-domain peptide) but also by
      fibronectin or interleukin-6 to lower concentrations. This action of SP was
      prevented by inhibitors of phospholipase C, of the inositol 1,4,5-trisphosphate
      receptor-mediated release of Ca(2+) from intracellular stores, and of Ca(2+)- and
      calmodulin-dependent protein kinase II (CaM-PK II). CONCLUSIONS: These results
      indicate that SP, acting at the neurokinin type 1 receptor, functions as an
      important modulator of corneal epithelial wound healing by activating CaM-PK II
      in epithelial cells and thereby sensitizing them to the induction of migration by
      various biological agents. They also provide important insight into a new
      strategy for the treatment of corneal wounds.

PMID- 15728537
TI  - Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in
      keratoconus corneas: evidence that oxidative stress plays a role in this
      disorder.
AB  - PURPOSE: The mRNA levels of antioxidant enzymes, matrix metalloproteinases,
      cathepsin V/L2, and tissue inhibitor of matrix metalloproteinases (TIMPs) were
      determined in keratoconus and normal corneas. Protein levels or enzyme activities
      were analyzed when RNA levels were different. METHODS: A total of 25 physiologic
      (normal) and 32 keratoconus corneas were studied. mRNAs were analyzed by
      semiquantitative reverse transcription-polymerase chain reaction and Southern
      blot analysis. Proteins were assessed by immunohistochemistry and/or Western blot
      analysis. Catalase activity was measured in corneal extracts. Antioxidant enzymes
      examined were catalase, superoxide dismutase (SOD)-1, SOD3, glutathione
      reductase, glutathione S-transferase and aldehyde dehydrogenase 3A1. Degradative
      enzymes examined were cathepsin V/L2 and matrix metalloproteinase (MMP)-1, -2, 
      7, -9, and -14. Tissue inhibitor of matrix metalloproteinase (TIMP)-1, -2, and -3
      were also examined. RESULTS: Keratoconus corneas exhibited a 2.2-fold increase of
      catalase mRNA level (P < 0.01) and 1.8-fold of enzyme activity (P < 0.03); a 1.5
      fold increase of cathepsin V/L2 mRNA (P < 0.03) and abnormal protein
      distribution; and a 1.8-fold decrease of TIMP-1 mRNA (P < 0.05) and 2.8-fold
      decrease of protein (P < 0.0001) compared with normal (physiologic) corneas. RNA
      levels for other antioxidant and degradative enzymes were similar between normal
      and keratoconus corneas. CONCLUSIONS: Keratoconus corneas have elevated levels of
      cathepsins V/L2, -B, and -G, which can stimulate hydrogen peroxide production,
      which, in turn, can upregulate catalase, an antioxidant enzyme. In addition,
      decreased TIMP-1 and increased cathepsin V/L2 levels may play a role in the
      matrix degradation that is a hallmark of keratoconus corneas. The findings
      support the hypothesis that keratoconus corneas undergo oxidative stress and
      tissue degradation.

PMID- 15728540
TI  - Detection and subcellular localization of two 15S-lipoxygenases in human cornea.
AB  - PURPOSE: There are two human 15-lipoxygenases (LOX), 15-LOX-1 and -2, which
      convert arachidonic acid to 15S-hydroxyeicosatetraenoic acid (15S-HETE). The
      presence of both 15-LOXs in the human cornea prompted this study to delineate
      their roles in the human corneal epithelium. METHODS: Human corneal epithelia
      from donor corneas and a human corneal epithelial (HCE) cell line were used in [1
      (14)C]arachidonic acid incubations, Western blot analysis, and quantitative real
      time RT-PCR. Cell cultures of HCE were treated with 15S-HETE to measure its
      effect on cell growth. HCE cells were transfected with plasmids to express green
      fluorescent (GFP) fusion proteins of 15-LOX-1 and -2, and in vivo laser confocal
      microscopy was performed to determine the subcellular localization of the 15-LOX
      fusion proteins. RESULTS: [1-(14)C]Arachidonic acid incubations yielded 15S-HETE
      as the only LOX product. Treatment with 15S-HETE (5-10 microM) reduced growth
      rate and induced apoptosis in cultured HCE cells in a dose-dependent manner. 15
      LOX-2 but not 15-LOX-1 was detected by Western blot analysis, although we were
      able to detect similar levels of both 15-LOX mRNAs by real-time quantitative RT
      PCR. 15-LOX-1 and -2 proteins showed different subcellular expression patterns.
      15-LOX-2 GFP was expressed in the cytoplasm and nucleus (actively taken up into
      the nucleus). 15-LOX-1 GFP fusion protein expression was restricted to the
      cytoplasm. CONCLUSIONS: These findings indicate that 15-LOX-2 is the predominant
      15-LOX protein in human cornea, and its product, 15S-HETE, plays a role in
      cellular proliferation. Because the two 15-LOXs have different subcellular
      compartmentalization, the authors hypothesize that their products are also
      compartmentalized and therefore exert different molecular effects in the human
      corneal epithelium.

PMID- 15728539
TI  - Doxycycline inhibits TGF-beta1-induced MMP-9 via Smad and MAPK pathways in human
      corneal epithelial cells.
AB  - PURPOSE: To evaluate the effects of TGF-beta1 and doxycycline on production of
      gelatinase MMP-9 and activation of Smad, c-Jun N-terminal kinase (JNK),
      extracellular-regulated kinase (ERK), and p38 mitogen-activated protein kinase
      (MAPK) signaling pathways in human corneal epithelial cells. METHODS: Primary
      human corneal epithelial cells were cultured to confluence. The cells were
      treated with different concentrations of TGF-beta1 (0.1, 1, or 10 ng/mL), with or
      without TGF-beta1-neutralizing mAb (5 microg/mL), SP600125 (30 microM), PD98059
      (40 microM), SB202190 (20 microM), or doxycycline (5-40 microg/mL) for different
      lengths of time. Conditioned media were collected from cultures treated for 24 to
      48 hours to evaluate the MMP-9 production by zymography and activity assay. Total
      RNA was isolated from cells treated for 6 to 24 hours to evaluate MMP-9
      expression by semiquantitative RT-PCR and Northern hybridization. Cells treated
      for 5 to 60 minutes were lysed in RIPA buffer for Western blot with phospho
      specific antibodies against Smad2, JNK1/2, ERK1/2, or p38. RESULTS: TGF-beta1
      increased expression, production, and activity of MMP-9 by human corneal
      epithelial cells in a concentration-dependent fashion. TGF-beta1 also induced
      activation of Smad2, JNK1/2, ERK1/2, and p38 within 5 to 15 minutes, with peak
      activation at 15 to 60 minutes. Doxycycline markedly inhibited the TGF-beta1
      induced production of MMP-9 and activation of the Smad, JNK1/2, ERK1/2, and p38
      signaling pathways. Its inhibitory effects were of a magnitude similar to
      SP600125, PD98059, and SB202190, specific inhibitors of the JNK1/2, ERK1/2, and
      p38 pathways, respectively. CONCLUSIONS: These findings demonstrated that
      doxycycline inhibits TGF-beta1-induced MMP-9 production and activity, perhaps
      through the Smad and MAPK signaling pathways. These inhibitory effects may
      explain the reported efficacy of doxycycline in treating MMP-9-mediated ocular
      surface diseases.

PMID- 15728541
TI  - Upper and lower eyelid saccades describe a harmonic oscillator function.
AB  - PURPOSE: To determine whether experimentally measured upper and lower eyelid
      saccades can be fitted to a mathematical function. METHODS: A charge-coupled
      device video camera connected to a personal computer was used to record upper and
      lower eyelid saccades accompanying 20 degrees and 40 degrees of vertical eye
      rotation in 19 normal adult subjects. Movement analysis was performed with
      software that calculated the center of a blue spot in each frame. The damped
      harmonic oscillator model was used to fit all saccadic functions obtained.
      RESULTS: All downward and upward saccades of both upper and lower eyelids were
      fitted with the underdamped solution of the model with correlation coefficients
      ranging from 0.980 to 0.999 (mean = 0.995). It was possible to measure maximum
      velocity at any time, amplitude, and duration of the saccade movements. For the
      upper eyelid, downward saccades were faster than upward saccades, a difference
      that was not observed for the lower eyelid. For both the upper and lower eyelids,
      the velocity of upward and downward movements reached a peak at approximately
      0.05/0.06 second and then decreased. For both the upper and lower eyelid
      saccades, there was good linear correlation between amplitude and velocity.
      Overshoots were detected in the downward saccades of both lids. CONCLUSIONS:
      Normal upper and lower saccades are described by functions that are extremely
      well fitted by the underdamped solution of the harmonic oscillator model.
      Overshooting is a typical feature of normal downward saccades and can be
      explained by the elastic properties of the tissues.

PMID- 15728542
TI  - SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye.
AB  - PURPOSE: Protein and peptides in tears play an important role in ocular surface
      diseases. In previous studies, changes have been demonstrated in the
      electrophoretic protein profiles of patients with dry eye. The purpose of this
      work was to determine the usefulness of surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip
      Array (Ciphergen Biosystems, Inc., Fremont, CA) technology for the automated
      analysis of proteins and peptides in tear fluid. METHODS: Patients with dry eye
      (DRY, n = 88) and healthy subjects (CTRL, n = 71) were examined. Their tear
      proteins were analyzed using SELDI-TOF-MS ProteinChip Arrays with three different
      chromatographic surfaces (CM10 cation exchange, Q10 anion exchange, and H50
      reversed-phase) prepared by means of a laboratory liquid-handling robotic
      workstation. The data were analyzed by multivariate statistical techniques and
      artificial neural networks, and the most important biomarkers were purified and
      identified by tandem MS. RESULTS: Complex patterns of tear proteins and peptides
      were detected. The different chromatographic surfaces revealed the selective
      enrichment of proteins such as lipocalin and lysozyme. Discriminant analysis
      demonstrated highly significant changes in the protein profiles in patients with
      dry eye (P < 0.001). With a seven-peptide multimarker panel, an artificial neural
      network could differentiate between patients with dry eye and healthy individuals
      with a specificity and sensitivity of 90%. The identification of biomarkers
      revealed an increase of inflammatory markers in patients with dry eye and a
      decrease of some proteins that may have protective functions. CONCLUSIONS: The
      SELDI-TOF-MS technology seems to be ideally suitable for the mass screening of
      peptides and proteins in tears. This highly sensitive approach dramatically
      reduces the analysis time and provides protein profiles with great mass accuracy.
      Thus, it may become a very useful tool in the search for potential biomarkers for
      diagnosis and new therapeutics in ocular diseases such as dry eye.

PMID- 15728543
TI  - Systemic reduction in glutathione levels occurs in patients with primary open
      angle glaucoma.
AB  - PURPOSE: To assess the level of plasma glutathione in patients with untreated
      primary open-angle glaucoma. METHODS: Twenty-one patients with newly diagnosed
      primary open-angle glaucoma and 34 age- and gender-matched control subjects were
      subjected to a blood analysis to detect the level of circulating glutathione in
      its reduced and oxidized forms. The effect of age, gender, and systemic blood
      pressure on circulating glutathione levels was also analyzed. RESULTS: Age had a
      negative effect on the level of both reduced and total glutathione (P = 0.002, r
      = -0.52 and P = 0.002, r = -0.52, respectively) in control subjects but not in
      patients with glaucoma (P > 0.05, r = 0.27, and P > 0.05, r = 0.22,
      respectively). In the control group, men demonstrated higher levels of both
      reduced and total glutathione than did women (P = 0.024 and P = 0.032,
      respectively). After correction for age and gender influences on blood
      glutathione levels, patients with glaucoma exhibited significantly lower levels
      of reduced and total glutathione than did control subjects (P = 0.010, F = 7.24
      and P = 0.006, F = 8.38, respectively). No differences between study groups were
      observed in either oxidized glutathione levels or redox index (P > 0.05, F =
      0.50; and P > 0.05, F = 0.30, respectively). CONCLUSIONS: Patients with glaucoma
      exhibit low levels of circulating glutathione, suggesting a general compromise of
      the antioxidative defense.

PMID- 15728544
TI  - Effect of glatiramer acetate on primary and secondary degeneration of retinal
      ganglion cells in the rat.
AB  - PURPOSE: After crush injury to the optic nerve, elevated intraocular pressure,
      and glutamate toxicity, the immune modulator glatiramer acetate (GA, Cop-1;
      Copaxone; Teva Pharmaceutical Industries, Pitach Tikva, Israel) has been shown to
      reduce the delayed cell death of retinal ganglion cells (RGCs). This study was
      undertaken to confirm the protective effect of GA on secondary degeneration of
      RGCs in the rat, by using a spatial, rather than temporal, model. METHODS: A
      total of 131 Wistar rats divided into 10 groups underwent bilateral stereotactic
      injection of fluorescent tracer (Fluorogold; Fluorochrome, Denver, CO) into the
      superior colliculus to label RGCs. They received a concurrent subcutaneously
      injection of (1) GA mixed with complete Freund's adjuvant (CFA), (2) CFA alone,
      or (3) saline. One week later, the superior one third of the left optic nerve was
      transected in animals in the six partial transection groups. Optic nerves in four
      additional groups underwent full transection. Rats were killed and retinas
      harvested from both eyes 1 or 4 weeks after partial transection and 1 or 2 weeks
      after full transection. RGC densities were calculated from retinal wholemounts,
      and differences between right (control) and left (transected) eyes were compared
      across treatment groups. RESULTS: Among the partial transection groups,
      differences in the mean percentage of RGC loss in the inferior retinas were not
      significant at 1 or 4 weeks (ANOVA; P = 0.20, P = 0.12, respectively). After full
      transection, there was significantly more RGC loss in the GA group than in the
      CFA group when comparing whole retinas at 1 week, but not at 2 weeks (two-tailed
      t-test; P = 0.04, P = 0.36, respectively). CONCLUSIONS: There is no evidence that
      GA has a neuroprotective effect after optic nerve transection, either for
      primarily injured or secondarily involved RGC.

PMID- 15728545
TI  - Analysis of retinal nerve fiber layer and optic nerve head in glaucoma with
      different reference plane offsets, using optical coherence tomography.
AB  - PURPOSE: To evaluate the performance of retinal nerve fiber layer (RNFL)
      thickness and optic nerve head (ONH) parameters analyzed with different offsets
      of reference plane in detecting early glaucomatous changes and in correlation
      with visual function using optical coherence tomography (OCT). METHODS: This was
      a cross-sectional study consisting of 41 normal subjects and 30 with early and 40
      with advanced glaucoma. RNFL thickness and ONH parameters were measured with
      reference planes positioned at 95, 150, and 205 microm above the level of retinal
      pigment epithelium (RPE). Discriminating power for early glaucoma detection and
      correlation with visual field MD for each parameter at different levels of
      reference plane were compared by using the analyses of area under the receiver
      operating characteristic curves (AUCs) and linear regression, respectively.
      RESULTS: All ONH measurements were significantly different between normal and
      glaucoma groups, irrespective of the level of reference plane. In normal eyes,
      changing the reference plane position resulted in significant differences in ONH
      measurements. Among all the parameters examined, integrated rim volume and RNFL
      thickness measured at 150 microm above the RPE showed the largest AUC (0.966) for
      early glaucoma detection, and the strongest correlation with visual function (r =
      0.793), respectively. CONCLUSIONS: OCT analysis of the ONH and RNFL is useful for
      early glaucoma detection. Among the three reference planes examined in this
      study, measurements analyzed at 150 microm above the RPE demonstrated the best
      performance for glaucoma detection and correlation with visual function. Compared
      with ONH measurements, RNFL thickness may be a better indicator, reflecting
      retinal ganglion cell function and monitoring disease progression.

PMID- 15728546
TI  - Immunosuppressive factors secreted by human amniotic epithelial cells.
AB  - PURPOSE: Amniotic membrane has been applied to the ocular surface to restore
      corneal function. The beneficial effect of amniotic membrane transplantation may
      be due to the immunosuppressive effects of amniotic epithelial cells. The purpose
      of this study was to determine whether amniotic epithelial cells (AECs) secrete
      anti-inflammatory and antiproliferative factors that affect the chemotaxis of
      neutrophils and macrophages and suppress both T- and B-cell proliferation in
      vitro. METHODS: Human amniotic cells were isolated from human amniotic membrane
      and cultured in vitro. The supernatants from AEC cultures were collected after 48
      hours of incubation. Neutrophil and macrophage chemotactic activity was tested in
      the presence of AEC supernatant, using 24-well migration assay chambers.
      Lymphocyte proliferation was tested by H(3)-thymidine incorporation. Apoptosis
      was examined by caspase-3 and annexin V assays, and expression of cytokines was
      assessed by RT-PCR. RESULTS: AEC supernatant significantly inhibited the
      chemotactic activity of neutrophils and macrophages toward macrophage
      inflammatory protein (MIP)-2 (P < 0.05). The supernatant significantly reduced
      the proliferation of both T and B cells after mitogenic stimulation (P < 0.05).
      Caspase-3 assays revealed that the supernatant induced apoptosis of T and B
      cells, but not of corneal epithelial cells and liver cells. In contrast to
      lymphocytes, macrophages and neutrophils were resistant to apoptosis induced by
      AEC supernatant. The AECs expressed message for TNFalpha, Fas ligand (FasL),
      TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TGFbeta, and
      macrophage migration-inhibitory factor (MIF). However, AEC induction of apoptosis
      was inhibited (50%) by anti-FasL antibody but not by anti-TRAIL or anti-TNFalpha
      antibodies. Moreover, AEC supernatant inhibited macrophage migration in vitro.
      CONCLUSIONS: AECs secrete soluble factors that inhibit cells in both the innate
      and adaptive immune systems.

PMID- 15728547
TI  - Thrombospondin plays a vital role in the immune privilege of the eye.
AB  - PURPOSE: The role of thrombospondin (TSP)-1 in TGF-beta activation and T-cell
      suppression was studied in the retinal pigment epithelial (RPE) cells, a
      monolayer of pigmented cells that line the subretinal space, an immune-privileged
      site in the eye. METHODS: Posterior eyecups were prepared by excising the
      anterior segment, lens, and retina from enucleated eyes of C57BL/6,
      thrombospondin-1 knockout (TSP-1KO), and TGF-beta2 receptor II double-negative
      (TGF-beta2 RII DN) mice, leaving behind a healthy monolayer of RPE resting on
      choroid and sclera. Serum-free medium was added to these RPE eyecups, and, after
      various time intervals, supernatants (SNs) were removed and tested. RESULTS: SNs
      of an ex vivo culture of RPE cells from C57BL/6 mice were shown to inhibit both
      antigen and anti-CD3 activation of T cells, partially due to constitutive
      production of TGF-beta and to the ability of RPE to activate the latent form of
      TGF-beta. Activation of TGF-beta was entirely dependent on TSP-1, also produced
      by RPE. SNs of RPE from TSP-1KO mice failed to inhibit T-cell activation.
      Ovalbumin (OVA)-specific delayed hypersensitivity (DH) was not impaired when OVA
      was injected either into the subretinal space or into the anterior chamber of TSP
      1KO mice before OVA immunization. Moreover, experimental autoimmune uveoretinitis
      was significantly more intense in eyes of TSP-1KO mice and failed to undergo
      spontaneous resolution unlike wild-type mice. CONCLUSIONS: Production of both TSP
      1 and active TGF-beta by RPE is essential to the creation and maintenance of
      immune privilege in the subretinal space and that the immune privilege limits the
      severity and duration of retinal inflammation due to autoimmunity.

PMID- 15728548
TI  - The effect of cataract surgery on postural control.
AB  - PURPOSE: Falls are a significant cause of morbidity in the elderly. Because
      decreased vision is known to be a significant risk factor for falling in this age
      group, we sought to examine the effect of the removal of cataract, a major cause
      of visual handicap, on postural stability. METHODS: Postural stability was
      measured in 23 patients who underwent cataract surgery, before and 1 to 4 months
      after surgery. Stability indices included Stability Effect, Fourier Spectrum of
      Postural Sway, and Synchronizations, and, based on these measurements, Falling
      Index, which had been shown in earlier studies to predict the risk of falling.
      RESULTS: Visual acuity in the surgical eye significantly improved in all patients
      after surgery (P < 0.01) and did not change in the fellow eye. Stability improved
      in most patients (19/23) and Fourier Spectrum of Postural Sway improved in the
      high-frequency bands (above 0.5 Hz), when viewing with the surgical eye, but not
      when viewing with the nonsurgical eye (P < 0.05). By Falling Index, before
      surgery, 12 of 23 patients were at high risk of falling, and only six were at low
      risk. After surgery, 16 of 23 were at low risk and only three remained at high
      risk (chi(2) test, P < 0.008). CONCLUSIONS: Cataract surgery significantly
      improves postural stability. Considering the high cost of treating fall-related
      injuries in the elderly, the findings may imply that cataract surgery is cost
      effective in this regard.

PMID- 15728549
TI  - Characterization and functional activity of thrombin receptors in the human lens.
AB  - PURPOSE: To investigate the expression of thrombin receptors in the human lens,
      the activation of downstream signaling pathways, and the ability of thrombin to
      regulate lens cell growth. METHODS: Thrombin receptor function in the human lens
      was determined first by measuring changes in intracellular calcium in response to
      thrombin and protease-activated receptor-activating peptides (PAR-APs). In the
      human capsular bag model, cell growth was assessed by phase microscope inspection
      of the cell coverage of the posterior capsular surface. In the human lens cell
      line FHL124, it was assessed by [(3)H]thymidine incorporation. Changes in p42/p44
      ERK phosphorylation (p-ERK) and protein kinase B (PKB/Akt) phosphorylation (p
      Akt) were monitored by Western blot. Reverse transcription-polymerase chain
      reaction (RT-PCR) applied to isolated lens epithelia and ex vivo capsular bag
      preparations as well as FHL124 cells determined expression of mRNA for the PARs.
      RESULTS: Brief exposures to thrombin (10 nM) and PAR1-AP (10 microM) induced an
      increase in cytosolic calcium in both anterior and equatorial lens cells, but
      activating peptides for PAR2, -3, and -4 failed to produce responses. Repeated
      exposure to thrombin produced a significant increase in cell coverage in the
      capsular bag model and increased [(3)H]thymidine incorporation into FHL124 cells.
      In the latter, exposure to thrombin (10 nM) and PAR1-AP (10 microM) induced
      biphasic increases in the phosphorylation of p42/p44 (p-ERK), with peak responses
      at 20 minutes and 12 hours. Thrombin also produced a 20-fold increase in p-Akt at
      12 hours compared with the control, whereas PAR1-AP (10 microM) induced a much
      smaller response. PAR1-AP did not induce a significant increase in
      [(3)H]thymidine incorporation and PAR2-AP, PAR3-AP, and PAR4-AP failed to
      reproduce any of the thrombin-stimulated effects. mPAR1 and -3 were expressed in
      native lens cells, and this expression was conserved in ex vivo capsular bag
      preparations as well as in FHL124 cells. CONCLUSIONS: This study identifies
      thrombin receptors coupled to calcium, ERK, and Akt signaling that modulate
      growth in native lens tissue and cultured cells, and it appears that the PAR1
      subtype is mainly responsible. PAR3 mRNA was also detected, but the receptor
      itself, if present, was not coupled to the above signaling elements.

PMID- 15728550
TI  - The peptides ADNF-9 and NAP increase survival and neurite outgrowth of rat
      retinal ganglion cells in vitro.
AB  - PURPOSE: Recent studies demonstrated that short peptides derived from activity
      dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective
      protein (ADNP) are neuroprotective at femtomolar concentrations. We evaluated
      these findings in cultures of purified rat retinal ganglion cells (RGCs) using
      two such peptides: ADNF-9 and NAP. In a second step, the influence of these
      peptides on neurite outgrowth in retinal explants was investigated. METHODS:
      Retinal ganglion cells (RGCs) were purified from newborn (postnatal day [P]0-P2)
      rat retina by immunopanning with antibodies against Thy1.1 and were cultured in
      serum-free N2 medium for 2 days. RGCs were treated with ADNF-9 and NAP at
      concentrations ranging from 10(-18) to 10(-10) M. Survival was quantified by
      counting viable cells by phase-contrast microscopy. Retinal explants from
      postnatal (P9-P11) rats were cultured in three-dimensional fibrin clots in serum
      free medium for 3 days. Explants were treated with 1 microM NAP or 1 microM ADNF
      9. Neurite outgrowth was visualized by staining with Sudan black and quantified
      by measuring axonal length. RESULTS: Both peptides enhanced survival of RGCs in a
      dose-dependent manner. ADNF-9 showed a maximum effect at 0.1 pM with an increase
      in survival to 177% (95% confidence interval: 149-204) of the control level. The
      EC(50) was 10.9 fM. NAP showed a maximum effect at 5 pM with an increase in
      survival to 167% (146-189) and an EC(50) of 6.1 fM. In the explants, 1 microM
      ADNF-9 enhanced axonal outgrowth to 126% (118-133) and 1 microM NAP to 117% (98
      137) compared with the control. CONCLUSIONS: Both peptides, ADNF-9 and NAP, not
      only increase RGC survival in vitro but also support neurite outgrowth in retinal
      explants. These peptides deserve further attention as potential neuroprotective
      compounds in retinal and optic nerve diseases.

PMID- 15728551
TI  - Spontaneous fluid transport across isolated rabbit and bovine ciliary body
      preparations.
AB  - PURPOSE: To quantify spontaneous fluid transport across the isolated ciliary
      bodies of rabbit and bovine and to determine their osmotic permeabilities.
      METHODS: A complete annulus of ciliary body was mounted in a custom-designed
      chamber appropriate for detecting net fluid movement across the in vitro
      preparation. RESULTS: A net fluid flow in the blood-to-aqueous direction was
      measured. It was generally observed that tissue freshness is a critical parameter
      for detection of such flow. The spontaneous, baseline fluid transport rate
      lasted, on average, approximately 4 hours. This flow solely reflects the
      secretory activity of the isolated ciliary epithelium, since the in vitro
      arrangement precludes contributions from ultrafiltration. Both the isolated
      rabbit and bovine ciliary body epithelia transported fluid in the absence of an
      external osmotic or pressure gradient. After corrections for area and possible
      collapse of the processes, a total flux rate of approximately 23 microL/hour or
      13% of the in vivo flow in rabbit was estimated. This value agrees with
      predictions of ionic fluxes and short-circuit current measurements, which are
      also obtained in vitro. The fluid flow is bicarbonate dependent in rabbit and
      chloride dependent in bovine, consistent with ionic transport mechanisms
      described in these species. Ouabain inhibited the fluid flow across both species,
      indicating dependence on active ionic transport. Irrespective of the spontaneous
      fluid transport, a flow elicited by an osmotic gradient allowed for a calculation
      of the osmotic permeability coefficient (P(f); approximately 10(-3) cm/s) in line
      with reports in other epithelia. In addition, mannitol permeability (5.6 x 10(-6)
      cm/sec) was similar to that measured in "tight" epithelia, as determined by
      measurements of radiolabeled fluxes of the sugar across rabbit ciliary bodies
      mounted in the chambers used for the present fluid transport study. CONCLUSIONS:
      This work demonstrates that isolated ciliary epithelial preparations transport
      fluid in the blood-to-aqueous direction. The present observations suggest that
      mounting arrangements for measuring volumetric fluid flow across the ciliary
      epithelium is suitable for future studies directed toward the pharmacological
      control of secretion.

PMID- 15728552
TI  - Inhibition of swelling-activated Cl- currents by functional anti-ClC-3 antibody
      in native bovine non-pigmented ciliary epithelial cells.
AB  - PURPOSE: To determine the potential role of ClC-3, a PKC-inhibitable Cl(-)
      channel, in mediating the swelling-activated Cl(-) current (I(Cl,swell)) of
      native bovine nonpigmented ciliary epithelial (NPE) cells. METHODS: Native bovine
      NPE cells were freshly harvested by enzymatic digestion. Whole-cell currents were
      recorded by patch-clamp measurements either in the presence or absence of a
      functional anti-ClC-3 antibody. RESULTS: Baseline whole-cell currents were small
      under isotonic conditions. Hypotonic cell swelling stimulated outwardly
      rectifying I(Cl,swell), which was reversibly inhibited by the Cl(-) channel
      blockers, phloretin (300 microM) or 5-nitro-2-(phenylpropylamino)-benzoate (NPPB,
      100 microM). Intracellular dialysis with anti-ClC-3 C(670-687) antibody did not
      affect baseline currents, but significantly delayed and inhibited hypotonic
      stimulation of I(Cl,swell). Preabsorption of the antibody with its antigen
      prevented the inhibition of I(Cl,swell) by antibody. In addition, intracellular
      dialysis with control Ex(133-148) antibody did not affect the I(Cl,swell).
      Moreover, activation of PKC by pretreatment with 100 nM phorbol 12,13-dibutyrate
      (PDBu) significantly inhibited the initial stimulation of I(Cl,swell), but had no
      effects on the steady state currents. CONCLUSIONS: The results suggest that
      endogenous ClC-3 is involved in mediating I(Cl,swell) of native bovine NPE cells.
      The delayed stimulation of I(Cl,swell) by PDBu may reflect upregulation of
      swelling-activated Cl(-) channels of different subtypes, especially when the
      function of ClC-3 is blocked. This information will be useful in understanding
      the mechanisms controlling aqueous humor formation and thereby intraocular
      pressure.

PMID- 15728553
TI  - Light-induced retinal vascular damage by Pd-porphyrin luminescent oxygen probes.
AB  - PURPOSE: The phosphorescence lifetime of certain metalloporphyrins dissolved in a
      physiological medium provides an optical signature for local oxygen concentration
      (pO(2)). This effect is used for measuring physiological pO(2) levels in various
      tissues. However, the phosphorescence quenching of certain metalloporphyrin
      triplet states by oxygen also creates singlet oxygen, which is highly reactive
      and capable of inducing tissue damage. In the current study, the Pd-meso-tetra(4
      carboxyphenyl) porphyrin dye (PdTCPP) was simultaneously used as an oxygen sensor
      and a photosensitizer. Phototoxicity was assessed in the eye fundus and
      correlated with tissue oxygenation, drug-light dose, and severity of tissue
      damage. METHODS: The kinetics of photochemical oxygen depletion during PdTCPP
      excitation was measured in vivo on the optic disc of piglets by phosphorescence
      lifetime imaging. Blood-retinal barrier breakdown and tissue damage were assessed
      by confocal and electron microscopy. RESULTS: For a retinal irradiance of 5
      mW/cm(2) at 532 nm and an injected PdTCPP dose of 20 mg/kg, the mean
      phosphorescence lifetime measured at the optic disc increased from 100 to 600
      micros within 8 minutes of continuous illumination. This corresponds to a
      decrease of pO(2) from 25 to 0 mm Hg, induced by a light dose of only 2.4
      J/cm(2). An exposure time of 6 minutes (1.8 J/cm(2)) generated an increase in
      phosphorescence lifetime from 100 to 400 micros, corresponding to a decrease in
      pO(2) from 25 to 4 mm Hg. This caused edema in all retinal layers, whereas
      irradiation of 2 minutes (0.6 J/cm(2)) damaged blood vessels and induced edema in
      the inner nuclear layer only. Heavy redistribution of occludin occurred after a
      30-minute exposure time (9 J/cm(2)). CONCLUSIONS: PdTCPP is potentially
      phototoxic under certain experimental conditions and can induce damage in
      peripapillary retina and optic nerve head after light exposure. The severity of
      tissue damage correlates with the phosphorescence measurements.

PMID- 15728554
TI  - Cyclic AMP prevents retraction of axon terminals in photoreceptors prepared for
      transplantation: an in vitro study.
AB  - PURPOSE: Cell transplantation has emerged as a possible remedy for degeneration
      and injury in the central nervous system (CNS). In the retina, photoreceptor
      transplantation is a potential treatment for retinal degenerative disease. Graft
      survival has been well documented, but evidence of functional recovery is
      lacking. A major obstacle to recovery of vision is lack of synapse formation
      between grafted photoreceptors and host bipolar and horizontal cells. A prior
      study demonstrated that photoreceptors prepared for transplantation undergo rapid
      morphologic changes, including retraction of axon terminals toward their cell
      bodies, away from potential synaptic partners, a phenomenon that may interfere
      with graft-host synaptic interaction after transplantation. In this study,
      prevention of retraction of photoreceptor axon terminals was possible by
      pharmacological intervention. METHODS: Photoreceptor sheets, prepared by
      vibratome sectioning, and full-thickness retinas, harvested from adult porcine
      eyes, were maintained in culture and treated with either the cyclic adenosine
      monophosphate analogue 8-(4-chlorophenylthio)-cyclic 3',5'-adenosine
      monophosphate (CPT-cAMP), or forskolin, an adenylyl cyclase stimulant, for up to
      48 hours. RESULTS: Both CPT-cAMP and forskolin treatments successfully blocked
      retraction of photoreceptor axon terminals. This effect was not due to cell
      toxicity and was reversed after removal of treatment, indicating its specificity.
      CONCLUSIONS: Pharmacological manipulation of photoreceptor axonal plasticity may
      improve graft-host synaptic interaction after subretinal photoreceptor cell
      transplantation.

PMID- 15728555
TI  - Use of optical coherence tomography to assess variations in macular retinal
      thickness in myopia.
AB  - PURPOSE: To investigate the variation in macular retinal thickness in otherwise
      normal young Asian myopic subjects by using optical coherence tomography (OCT).
      METHODS: One hundred thirty ophthalmically normal men 19 to 24 years of age with
      myopia (spherical equivalent, -0.25 to -14.25 D) underwent examination of one
      randomly selected eye. Visual acuity, refraction, slit lamp examination,
      applanation tonometry, gonioscopy, A-scan ultrasound, fundus examination, visual
      field testing, and optic disc photography were performed. Exclusion criteria were
      visual acuity worse than 20/30, previous intraocular surgery, intraocular
      pressure >21 mm Hg, or other ocular diseases. Three horizontal transfixation and
      three vertical transfixation OCT scans (ver.4.1; Carl Zeiss Meditec, Dublin, CA)
      of 6 mm each were conducted on each eye by a single operator. Neurosensory
      retinal thicknesses at 100 points along each scan were measured, and the overall
      average, maximum, and minimum retinal thicknesses were analyzed by simple linear
      regression and analysis of variance. RESULTS: The average macular retinal
      thickness (overall) was 230.9 +/- 10.5 microm and was not significantly related
      to the degree of myopia. The mean maximum retinal thickness (at the parafovea)
      was 278.4 +/- 13.0 microm, and correlated negatively with axial length (P =
      0.03). The mean minimum retinal thickness (at the foveola) was 141.1 +/- 19.1
      microm, and this was positively correlated with axial length (P = 0.015) and
      spherical equivalent (P = 0.0002). The retina was thicker at the superior and
      nasal parafovea compared to the inferior or temporal parafovea. CONCLUSIONS:
      Average retinal thickness of the macula does not vary with myopia. However, the
      parafovea was thinner and the fovea thicker with myopia.

PMID- 15728556
TI  - Sulforaphane induces thioredoxin through the antioxidant-responsive element and
      attenuates retinal light damage in mice.
AB  - PURPOSE: Thioredoxin (Trx) is a multifunctional endogenous redox regulator that
      protects cells against various types of cellular or tissue stresses. This study
      was conducted to test whether sulforaphane (SF), a naturally occurring
      isothiocyanate that is highly concentrated in broccoli sprouts, induces Trx in
      retinal tissues and whether pretreatment with SF protects against light-induced
      retinal damage in mice. METHODS: Expression of Trx in mouse retina was analyzed
      by Western blot and immunohistochemistry. Retinal damage was induced by exposure
      to white light at 6000 lux for 2 hours. To estimate retinal cell damage, the
      number of cell nuclei and the percentage of TUNEL-positive cells were counted in
      the outer nuclear layer and the retinal pigment epithelial (RPE) layer and the
      electroretinograms recorded. To analyze further the mechanism of Trx induction by
      SF, cultured human K-1034 RPE cells were used. RESULTS: Both intraperitoneal and
      oral SF induced Trx protein in the neural retina and RPE. The maximum induction
      of Trx was observed with intraperitoneal SF 0.5 mg/d for 3 days. After exposure
      to light, mice pretreated with SF had a significantly lower percentage of TUNEL
      positive RPE and photoreceptor cells, a significantly higher number of RPE and
      photoreceptor nuclei, and greater amplitude of ERG a- and b-waves than in the
      saline-treated mice. In K-1034 cells, 1 microM SF induced Trx protein, whereas 10
      microM SF did not damage cells or augment cellular peroxide production, tested by
      a lactate dehydrogenase (LDH) release assay and 2',7'-dichlorofluorescein
      diacetate (DCFH-DA)/flow cytometry, respectively. In the luciferase reporter
      assay, the antioxidant-responsive element (ARE) played a role in SF-induced Trx
      expression. In the electrophoretic mobility shift assay, SF induced binding of
      Nrf2, small Maf, and c-Jun to the ARE of the Trx gene. CONCLUSIONS: SF induced
      Trx in murine retina and effectively reduced retinal light damage. Evidence
      suggests that the ARE is involved in the mechanism of Trx induction by SF in RPE
      cells.

PMID- 15728557
TI  - Laser-induced changes in intraretinal oxygen distribution in pigmented rabbits.
AB  - PURPOSE: To make the first measurements of intraretinal oxygen distribution and
      consumption after laser photocoagulation of the retina and to compare the
      efficiency of micropulsed (MP) and continuous wave (CW) laser delivery in
      achieving an oxygen benefit in the treated area. METHODS: Oxygen-sensitive
      microelectrodes were used to measure oxygen tension as a function of retinal
      depth before and after laser treatment in anesthetized, mechanically ventilated,
      Dutch Belted rabbits (n = 11). Laser lesions were created by using a range of
      power levels from an 810-nm diode laser coupled with an operating microscope
      delivery system. MP duty cycles of 5%, 10%, and 15% were compared with CW
      delivery in each eye. RESULTS: Sufficient power levels of both the CW and MP
      laser reduced outer retinal oxygen consumption and increased oxygen level within
      the retina. At these power levels, which correlated with funduscopically visible
      lesions, there was histologically visible damage to the RPE and photoreceptors.
      Retinal damage was energy dependent but short-duty-cycle MP delivery was more
      selective in terms of retinal cell damage, with a wider safety range in
      comparison with CW delivery. CONCLUSIONS: The relationship between laser power
      level and mode of delivery and the resultant changes in oxygen metabolism and
      oxygen level in the retina was determined. Only partial destruction of RPE and
      photoreceptors is necessary, to produce a measurable oxygen benefit in the
      treated area of retina.

PMID- 15728558
TI  - Basement membrane-dependent survival of retinal ganglion cells.
AB  - PURPOSE: The present study investigates the role of the inner limiting membrane
      (ILM) in the survival of ganglion cells (GCs) in embryonic chick and mouse
      retina. METHODS: In chick embryos, the ILM was enzymatically removed at embryonic
      day (E)5 and E7 in ovo, and GCs were counted over the following 7 days of
      incubation. In mice, the ILM ruptured early in development due to a targeted
      mutation of laminin-gamma1. The number of surviving GCs in late embryonic
      homozygous mutant mice was compared to GC counts in heterozygotic and nonmutant
      siblings. The survival of GCs was also assayed in vitro, using the ILM as a
      substrate. RESULTS: When the ILM was removed in E5 chick embryos, almost all GCs
      underwent apoptosis by E10. GC apoptosis was prevented by reconstituting the ILM
      shortly after its disruption. Apoptosis of retinal GCs also occurred in mouse
      embryos with a fragmented ILM. ILM disruption in both chick and mice not only
      affected GC survival but also led to the retraction of the end-feet processes of
      radial cells from the GC layer. In vitro, GCs thrived better on substrates of
      radial cell end feet than on plain ILM, indicating that the contact with the end
      feet is more important than the presence of the ILM for GC survival. CONCLUSIONS:
      The radial cell end feet are the natural substrate for GCs and are essential for
      their survival. The importance of the ILM lies in its function to anchor the
      radial end feet to the vitreal surface of the retina.

PMID- 15728559
TI  - Retinal disease in mice lacking hypoxia-inducible transcription factor-2alpha.
AB  - PURPOSE: To characterize ocular disease in HIF-2alpha-null mice. METHODS:
      Histologic, electroretinographic (ERG), and molecular studies were performed on
      samples obtained from age- and gender-matched HIF-2alpha-null (HIF-2alpha-KO),
      HIF-2alpha-heterozygous (HIF-2alpha-HET), and wild-type (WT) littermate mice.
      RESULTS: HIF-2alpha-KO mice exhibited marked thinning of the retina and abnormal
      retinal vasculature. The pathologic changes in HIF-2alpha-KO mice were associated
      with a virtual absence of postreceptor function. The expression of a surrogate
      marker for HIF-2alpha mRNA localized to vascular endothelial, amacrine, and
      retinal pigment epithelial (RPE) cells. Several HIF-2alpha target genes involved
      in angiogenesis, retinal protection, and stress responses have altered expression
      patterns in HIF-2alpha-KO retinas. CONCLUSIONS: HIF-2alpha-KO mice exhibit marked
      retinopathy consistent with complete loss of vision by 1 month of age. Impaired
      HIF-2alpha signaling in HIF-2alpha-KO mice likely produces functional deficits in
      cell types in which HIF-2alpha normally is expressed, ultimately resulting in
      retinopathy. Future studies will address whether the molecular abnormalities
      described in this study are directly responsible for the retinal disease in HIF
      2alpha-KO mice.

PMID- 15728560
TI  - Objective signs of photoreceptor displacement by binocular correspondence
      perimetry: a study of epiretinal membranes.
AB  - PURPOSE: To describe a method for quantitative mapping of metamorphopsia and
      abnormalities of oculocentric direction in subjects with epiretinal membranes.
      METHODS: Binocular correspondence perimetry was performed using red and green
      dichoptic stimuli applied in a rectangular grid pattern. The study included 9
      healthy subjects and 10 subjects with a unilateral premacular epiretinal membrane
      and a healthy fellow eye. Interocular visuospatial correspondence was expressed
      in a visuospatial deviation score and the binocular correspondence perimetry
      plots were displayed in proportion to fundus photographs. A reference interval
      was defined as the 95% CI for the average visuospatial deviation score in healthy
      subjects. RESULTS: In 6 out of 10 subjects with epiretinal membranes,
      visuospatial alignment deviated beyond the reference interval found in healthy
      subjects, whereas 4 subjects were within the normal range. The deviation score
      increased with decreasing visual acuity, although indications of heterogeneity of
      the subject population were identified, suggesting that visual acuity reduction
      and metamorphopsia may be dissociated in some types of epiretinal membranes.
      CONCLUSIONS: Binocular correspondence perimetry enables quantitative mapping of
      metamorphopsia and stratification of subjects with epiretinal membranes with
      respect to normative references. Data from healthy subjects appear to describe a
      physiological level of tolerance for changes in oculocentric direction, which may
      apply also to the changes induced by retinal traction.

PMID- 15728561
TI  - Measurement of macular pigment: Raman spectroscopy versus heterochromatic flicker
      photometry.
AB  - PURPOSE: There are several techniques for measuring macular pigment (MP) in vivo,
      of which Raman spectroscopy (RS) is a recently developed objective METHOD: This
      study reports the reproducibility, test-retest variability, and validity of RS MP
      readings, by comparing them with heterochromatic flicker photometry (HFP).
      METHODS: MP was measured with HFP and RS in 120 healthy subjects, and the latter
      technique was also used on two separate occasions in a sample of 20 subjects to
      investigate the intersessional variability of readings. Intrasessional
      reproducibility of RS MP measurements was also calculated. In addition, serum
      concentrations of lutein (L) and zeaxanthin (Z) were measured and correlated with
      both RS and HFP MP readings. RESULTS: Mean (+/-SD) MP in the right eye was 0.279
      +/- 0.145 and 0.319 +/- 0.155 with RS and HFP, respectively. The differences
      between corresponding MP readings taken on RS and HFP lay within the Bland-Altman
      95% limits of agreement for the two instruments in 93.6% and 94.4% of cases in
      the right and left eyes, respectively. Intrasessional reproducibility of RS
      readings, expressed as the coefficient of variation, was 8.42% +/- 7.12%. Ninety
      five percent of MP readings taken with RS on two separate occasions lay within
      the 95% limits of agreement for the two sessions. A positive, but insignificant,
      relationship was observed between RS and HFP MP readings and serum concentrations
      of L and Z (RS, P = 0.356; HFP, P = 0.540). CONCLUSIONS: RS, an objective method
      of measuring MP levels in vivo, exhibits acceptable reproducibility and test
      retest variability. The results demonstrated good correlation between RS and HFP
      measurements of MP, thus authenticating RS against a validated psychophysical
      technique of measuring MP. However, investigators should use only one of these
      instruments for the duration of any given study because of differences in the
      scientific rationale, and the factors that influence RS and HFP measurements of
      MP.

PMID- 15728562
TI  - Reduced foveolar choroidal blood flow in eyes with increasing AMD severity.
AB  - PURPOSE: In an earlier study, the authors reported that foveolar choroidal blood
      flow (ChBFlow) decreases in patients with AMD and drusen. To explore further the
      choroidal circulatory changes in patients with AMD, the relationship between
      ChBFlow and fundus features associated with increased risk of choroidal
      neovascularization (CNV) were investigated. METHODS: The study included 26
      control eyes of 17 normal subjects and 163 eyes with early AMD characteristics of
      123 patients with AMD. The AMD study eyes were divided into three groups
      according to increasing risk for development of CNV: (1) drusen > or =63 microm,
      no RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye;
      (2) drusen > or =63 microm, RPE hyperpigmentary changes in the study eye, and no
      CNV in the fellow eye; and (3) eyes with CNV in the fellow eye. Laser Doppler
      flowmetry was used to assess relative foveolar choroidal blood velocity (ChBVel),
      volume (ChBVol), and flow (ChBFlow). Differences in the mean circulatory
      parameters were assessed by analysis of variance (ANOVA) and test of linear
      trend. RESULTS: Mean ChBVel, ChBVol, and ChBFlow decreased with increased risk
      for CNV (linear trend, P < 0.05). The lowest circulatory parameters were observed
      in the eyes with the highest risk for CNV development. Trends for ChBVel and
      ChBFlow were still significant after adjustment for multiple factors.
      CONCLUSIONS: There is a systematic decrease in choroidal circulatory parameters
      with an increase in the severity of AMD features associated with risk for the
      development of CNV, suggesting a role for ischemia in the development of CNV.

PMID- 15728563
TI  - Mechanisms of apoptosis in human retinal pigment epithelium induced by TNF-alpha
      in conditions of heavy metal ion deficiency.
AB  - PURPOSE: To investigate the mechanism underlying apoptosis in retinal pigment
      epithelium (RPE) induced by TNF-alpha in conditions of heavy metal ion
      deficiency. METHODS: Apoptotic morphology was assessed with Hoechst 33342. FITC
      VAD-fmk or antibody specific to cleaved caspase 3 was used to detect in situ
      activated caspases or cleaved caspase 3, respectively. JC-1 and carboxylated
      dichlorodihydrofluorescein diacetate were used as probes to measure mitochondrial
      membrane potential (Deltapsi(m)) and intracellular reactive oxygen species (rOx).
      RESULTS: The apoptotic response of RPE cells was markedly enhanced when TNF-alpha
      plus actinomycin D (act-D) was coapplied with N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN), a heavy metal ion chelator. The apoptosis
      was caspase dependent, and a blockade with cyclosporin A (CsA), an inhibitor of
      the mitochondrial permeability transition (MPT), but not FK506, a calcineurin
      inhibitor, abolished caspase activation and subsequent apoptosis, suggesting that
      apoptosis requires the MPT, and that caspase activation is downstream to the MPT.
      MPT, observed in situ as Deltapsi(m) loss, was prevented when cells were
      pretreated with either CsA or the pan-caspase inhibitor z-VAD-fmk. This result
      suggests that apoptotic signaling is initiated by the MPT and further amplified
      by downstream caspases, probably through a feedback loop. An increase in rOx was
      observed in cells exposed to TNF-alpha+act-D+TPEN, and rOx production did not
      require MPT or caspase activation. In addition, application of antioxidants
      significantly inhibited rOx production, Deltapsi(m) loss, and apoptosis. These
      data suggest that the rOx may play a role as a proapoptotic signal. CONCLUSIONS:
      The data suggest that intracellular heavy metal ions play a role in determining
      the apoptosis induction threshold of the inflammatory response to TNF-alpha in
      RPE.

PMID- 15728564
TI  - Functional characterization and comparison of the outer blood-retina barrier and
      the blood-brain barrier.
AB  - PURPOSE: To determine efflux systems of the outer blood-retina barrier (oBRB) and
      compare the oBRB with the blood-brain barrier (BBB). METHODS: Porcine oBRB
      structure and transport characteristics of freshly dissected intact tissue sheets
      were investigated with scanning electron microscopy, immunocytochemistry, vital
      dye labeling, and pharmacological agents, using HPLC/mass spectrometry. To
      compare drug permeation across the oBRB and the BBB, three different systems were
      used: (1) oBRB tissue sheets in a two-chamber device in vitro; (2) an in vitro
      BBB model composed of purified astrocytes and brain capillary endothelial cells
      on transfilter membranes; and (3) an in vivo model based on the brain-plasma
      ratio of drugs in mice. RESULTS: Efflux pumps (multidrug resistance protein [P
      gp] and multidrug resistance-associated protein [MRP]) were demonstrated by
      antibody staining. Side-specific application of three P-gp and MRP substrates and
      selective transport inhibition suggested that both membrane proteins were
      preferentially located on the choroidal side of the oBRB. Therefore, the efflux
      was directed toward the blood, as in the BBB. To relate the transport
      characteristics of the oBRB to the BBB, up to nine different test compounds were
      used. The ranking of the permeability coefficients (P(e)) and the brain-plasma
      ratios of test compounds indicated that the oBRB has barrier and carrier features
      similar to those of the BBB in vitro and in vivo. CONCLUSIONS: Despite the fact
      that epithelial oBRB and endothelial BBB have developed as separate entities with
      many site-specific functions, their transport and permeation characteristics
      display surprising similarities, that include the polarized expression of the two
      major efflux pumps P-gp and MRP.

PMID- 15728565
TI  - Oxidant-induced apoptosis in human retinal pigment epithelial cells: dependence
      on extracellular redox state.
AB  - PURPOSE: To test whether variation in extracellular cysteine (Cys) redox
      potential (E(h)) over the physiologic range occurring in human plasma affects
      oxidant-induced apoptosis in cultured human retinal pigment epithelial (hRPE)
      cells. METHODS: The hRPE cells were incubated in culture medium with E(h)
      established over the range of -16 mV (most oxidized) to -158 mV (most reduced) by
      adding different concentrations of Cys and cystine (CySS) with constant total Cys
      equivalents. Apoptosis was induced with tert-butylhydroperoxide (tBH). RESULTS:
      The hRPE cells were sensitized to tBH-induced apoptosis in the more oxidized
      extracellular conditions (E(h) > -55 mV) compared with the reduced conditions
      (E(h) < -89 mV). Loss of mitochondrial membrane potential (Deltapsi(m)), release
      of cytochrome c, and activation of caspase 3 after tBH treatments all increased
      under the more oxidized conditions. However, the extracellular redox state did
      not affect expression of Fas or FasL in hRPE cells. CONCLUSIONS: The hRPE cells
      that are exposed to a more oxidized extracellular redox environment have
      increased susceptibility to oxidant-induced apoptosis through the intrinsic
      mitochondrial pathway, which could contribute to an age-related decline in cell
      populations in the retina and thereby provide a potential mechanism for the
      degenerative changes that are associated with age-related macular degeneration
      (ARMD).

PMID- 15728566
TI  - Vascular endothelial growth factor reduced and connective tissue growth factor
      induced by triamcinolone in ARPE19 cells under oxidative stress.
AB  - PURPOSE: To investigate whether triamcinolone acetonide (TA) affects the
      expression of vascular endothelial growth factor (VEGF) and connective tissue
      growth factor (CTGF) in retinal pigment epithelial (RPE) cells exposed to
      oxidative stress. METHODS: TA (10 nM, 1 microM, or 100 microM) was added to
      ARPE19 cells exposed to oxidative stress induced by hypoxia-reoxygenation and
      paraquat. Cellular expression of VEGF, CTGF, and an inducer of both growth
      factors, transforming growth factor (TGF)-beta was investigated with real-time
      reverse transcription-polymerase chain reaction and Western blot analysis. Tube
      forming assays were conducted with human umbilical vein endothelial cells
      (HUVECs) in conditioned medium from RPE cells exposed to oxidative stress, with
      or without TA treatment. RESULTS: Oxidative stress induced mRNA expression of
      VEGF, CTGF, and TGF-beta by RPE cells. TA reduced upregulation of VEGF and TGF
      beta in a concentration-dependent manner. In contrast, upregulation of CTGF by
      oxidative stress was accelerated by TA concentrations of 10 nM and 1 muM. Tube
      formation by HUVECs was strongly inhibited by exposure to conditioned medium from
      oxidative stress-stimulated ARPE19 cells treated with 1 muM TA compared with
      cells not treated with TA. CONCLUSIONS: TA reduced VEGF expression and induced
      CTGF expression in ARPE19 cells exposed to oxidative stress, and conditioned
      medium from these cells inhibited tube formation by HUVECs. Because VEGF is a
      major cytokine involved in angiogenesis, and CTGF is a main cytokine related to
      fibrosis, these results suggest that changes in their expression may be important
      mechanisms underlying the decreased choroidal neovascularization and fibrosis
      after administration of TA.

PMID- 15728567
TI  - The renin-angiotensin system and the developing retinal vasculature.
AB  - PURPOSE: To determine the location and activity of renin-angiotensin system (RAS)
      components in the developing rat retina and whether the RAS influences retinal
      vascularization. METHODS: Transgenic Ren-2 rats, which overexpress the RAS, and
      Sprague-Dawley (SD) rats were studied at postnatal day (P)1, P7, P14, P21, and
      P90. Immunohistochemistry was performed for angiotensinogen, prorenin,
      angiotensin II (Ang II), and the angiotensin type 1 (AT(1)) and 2 (AT(2))
      receptors. Retinal active renin and prorenin were measured by radioimmunoassay,
      and the density of angiotensin-converting enzyme (ACE) by autoradiography. At P1
      to P7, Ren-2 and SD rats were administered either the ACE inhibitor lisinopril
      (10 mg/kg per day, intraperitoneally [IP]) or the AT(1) receptor antagonist
      losartan (10 mg/kg per day, IP), and vessel length and density were measured.
      RESULTS: At all time points, RAS components were localized to blood vessels and
      cells in the ganglion cell layer. At P1, Ang II and both the AT(1) and AT(2)
      receptors were on hyaloid vessels. ACE binding increased in intensity from P1 to
      P90. Retinal renin was mainly activated and was 5- to 15-fold higher in Ren-2
      than in SD rats. In Ren-2 rats, the growing vasculature extended farther into the
      retinal periphery than in SD rats and was unchanged with either lisinopril or
      losartan. Vascular density was increased in the periphery of Ren-2 rats compared
      with SD rats and was reduced with lisinopril but not with losartan. CONCLUSIONS:
      In the developing rat retina, a complete RAS is mainly found in blood vessels and
      cells in the ganglion cell layer, where it may influence the early stages of
      vascularization.

PMID- 15728568
TI  - Selective suppression of pathologic, but not physiologic, retinal
      neovascularization by blocking the angiotensin II type 1 receptor.
AB  - PURPOSE: To investigate the anti-inflammatory and anti-angiogenic effects of
      telmisartan, an angiotensin II type 1 receptor (AT1-R) antagonist, on ischemia
      induced retinal neovascularization. METHODS: C57BL/6 neonatal mice were reared in
      an 80% concentration of oxygen from postnatal day (P)7 to P12, followed by room
      air breathing until P17, to induce ischemia-initiated retinal neovascularization
      (i.e., a murine model of ischemic retinopathy). Tissue localization of AT1-R was
      examined by immunohistochemistry for murine retinal wholemounts and human
      fibrovascular tissues excised at vitrectomy for proliferative diabetic
      retinopathy. Animals received intraperitoneal injection of telmisartan or
      vehicle. A concanavalin A lectin perfusion-labeling technique was used to
      evaluate the areas of physiological and pathologic retinal new vessels and the
      number of leukocytes adhering to the vasculature. Retinal mRNA and protein levels
      of intercellular adhesion molecule (ICAM)-1, vascular endothelial growth factor
      receptor (VEGFR)-1, and VEGFR-2 were examined by RT-PCR and ELISA. RESULTS:
      Vessels in human fibrovascular tissues and the murine retinas were positive for
      AT1-R. Pathologic (P < 0.01), but not physiologic (P > 0.05), retinal
      neovascularization was significantly suppressed in telmisartan-treated mice
      compared with vehicle-treated animals. The number of adherent leukocytes (P <
      0.01) was also significantly reduced, together with retinal ICAM-1 levels (P <
      0.01) in the telmisartan-treated group compared with the control group. No
      significant difference was detected in retinal VEGFR-2 levels between the two
      groups, whereas retinal VEGFR-1 levels in the telmisartan-treated group were
      significantly (P < 0.05) lower than in the vehicle-treated group. CONCLUSIONS:
      The present findings suggest that the AT1-R signaling blockade leads to the
      selective suppression of pathologic, but not physiological, retinal
      neovascularization through the inhibition of the inflammatory processes related
      to pathologic neovascularization.

PMID- 15728569
TI  - Heat shock protein 27 delays Ca2+-induced cell death in a caspase-dependent and 
      independent manner in rat retinal ganglion cells.
AB  - PURPOSE: Hsp27 is a well-characterized and studied antiapoptotic protein. A
      recent study reported that Hsp27 is upregulated in the retina after retinal
      ischemic preconditioning. The timing of this upregulation of Hsp27 correlates
      with the protective effects of the treatment. It was the goal of the current
      study to determine what role Hsp27 plays in this protection. METHODS: The rat
      homologue of Hsp27 (rHsp27) was overexpressed in a transformed rat retinal
      ganglion cell line and subjected to ischemic stress and calcium overload.
      RESULTS: The overexpression of rHsp27 increased cell survival and inhibited
      caspase-3 activation. However, the inhibition of caspase-3 alone had no effect on
      cell survival. Proteomic analysis after Ca(2+) overload identified four proteins
      that were repeatedly associated with rHsp27. These proteins include actin, Hsp70,
      eEF-1alpha, and SPIN-2. No association with cytochrome c or any caspase enzymes
      was detected. CONCLUSIONS: The results indicate that Hsp27 protects the retinal
      cells by both caspase-dependent and -independent mechanisms.

PMID- 15728570
TI  - Hsp27 upregulation by HIF-1 signaling offers protection against retinal ischemia
      in rats.
AB  - PURPOSE: Previous work from the authors' laboratory has shown that Hsp27 is
      specifically upregulated after retinal ischemic preconditioning (IPC), and this
      upregulation acts as a key cytoprotective factor in preventing retinal ischemic
      damage. The regulatory mechanisms involved in the upregulation of Hsp27 after IPC
      are unknown. The purpose of this study was to explore the transcriptional events
      responsible for the upregulation of Hsp27 after IPC. METHODS: CoCl(2) was used to
      test for Hsp27 expression after hypoxic stimulus. The promoter and first intron
      regions of the human Hsp27 gene were cloned by PCR and characterized by deletion
      analysis by using a reporter assay. In vitro results were then applied to an in
      vivo model of retinal ischemia to determine whether CoCl(2) upregulates rHsp27
      and protects the retina from ischemic injury. RESULTS: CoCl(2) upregulated Hsp27
      in cultured retinal neurons. Promoter-intron reporter assays using various DNA
      deletion constructs indicated that several HIF-1 binding sites were necessary for
      CoCl(2)-induced expression of the Hsp27 gene. Furthermore, CoCl(2) upregulated
      Hsp27 in the rat retina and protected the rat retina from ischemic injury.
      CONCLUSIONS: These data provide evidence that Hsp27 is regulated by hypoxic
      signaling through HIF-1 activation and support the idea that an early event in
      IPC is the activation of HIF-1. These findings are significant, because this is
      the first time HIF-1 activation has been associated with the protective effects
      of IPC and with Hsp27 upregulation.

PMID- 15728571
TI  - Improved contrast of peripapillary hyperpigmentation using polarization analysis.
AB  - PURPOSE: To improve detection and quantification of peripapillary
      hyperpigmentation, associated with aging, open-angle glaucoma, and age-related
      macular degeneration. METHODS: A computational approach was implemented with a
      readily available polarimeter used in glaucoma diagnosis, a nerve fiber analyzer
      (GDx; Laser Diagnostic Technologies, San Diego, CA). Using near-infrared
      illumination at each of 20 input polarizations, a series of image pairs was
      digitized. One image is made from the light returning from the eye that is
      polarized parallel to the input light, and the other image is made from the light
      that is rotated by 90 degrees from the input polarization. Using raw data from
      these 40 images, and a simplified model of ocular polarization properties, images
      were computed based on their polarization content. Regions of hyperpigmentation,
      selected using stereo color fundus photographs, were quantified in three types of
      polarimetry images: (1) a depolarized light image resulting mainly from multiply
      scattered light; (2) an average image that is typical of confocal images; and (3)
      a birefringence image. Measurements on versus off hyperpigmentation were made in
      nine persons with suspected glaucoma or patients with primary open-angle
      glaucoma, selected to have clinically visible hyperpigmentation. RESULTS: In the
      depolarized light images, hyperpigmented regions were significantly brighter than
      comparison areas (P < 0.0425)-that is, had more scattered light and therefore
      more contrast (P < 0.037) than did color or other polarimetric images.
      CONCLUSIONS: With this polarimetry imaging method, subretinal tissues such as
      those with hyperpigmentation can be visualized with increased contrast.

PMID- 15728572
TI  - Critical flicker frequency as a potential vision technique in the presence of
      cataracts.
AB  - PURPOSE: Potential vision testing attempts to predict the visual outcome that
      might be expected as a result of a cataract operation. This report details the
      clinical utility of critical flicker frequency (CFF) as a potential vision test
      (PVT). METHODS: CFF thresholds were determined in 31 subjects with age-related
      idiopathic cataract and no other eye disease, 19 subjects with macular disease
      (MD) and clear ocular media, and 24 age-matched control subjects. In addition,
      the CFF technique was administered before cataract surgery in 52 patients and
      compared with the information provided by presurgical case history and ocular
      examination alone (ophthalmological judgment [OJ]) and results from two commonly
      used PVTs (the retroilluminated pinhole and the potential acuity meter). RESULTS:
      CFF thresholds obtained in the nonsurgical cataract group were unrelated to
      cataract severity and were similar to those in the control group. In contrast,
      CFF scores were significantly related to visual acuity (VA) in the MD group. In
      the pre- and postsurgical studies, OJ predicted postoperative VA very well in
      patients with moderate cataract and normal fundi and better than all the PVTs. OJ
      performed less well in patients with comorbid eye disease and dense cataracts,
      when information from the PVTs would probably have been useful. CFF provided the
      most accurate predictions of postoperative VA in the small sample of patients
      with dense cataracts. CONCLUSIONS: CFF was unaffected by cataract, yet sensitive
      to MD, and provided useful information about the postoperative visual outcome
      beyond that obtained through history and ocular examination in patients with
      dense cataracts.

PMID- 15728573
TI  - Testing the role of gp96 as peptide chaperone in antigen processing.
AB  - gp96 is a 96-kDa glycoprotein of the endoplasmic reticulum that is believed to be
      involved in antigen processing as an intermediate carrier of peptides for
      presentation by major histocompatibility complex (MHC) class I molecules. This
      function implies that gp96 carries a large array of different peptides that
      represent the antigenicity of the cell and can serve all MHC class I molecules.
      So far, the evidence regarding these peptides is largely indirect and based on
      experiments where mice immunized with gp96 from tumor or virus-infected cells
      developed T cellular immune responses with the corresponding specificities. We
      analyzed by mass spectrometry peptides isolated from gp96 and found a number of
      different peptides derived from the proteins of different cellular compartments
      but mostly cytoplasm and nucleus. The sequences of these peptides provide
      information on the specificity of antigen processing and reveal structural
      requirements for binding to gp96 that only partially correspond to those of
      peptides presented by MHC class I molecules. The yield of peptides extracted from
      gp96 was far substoichiometric with an estimated occupancy of this chaperone of
      between 0.1% and 0.4%. These results strongly argue against a regular role for
      gp96 as a peptide chaperone in antigen processing.

PMID- 15728574
TI  - Structural basis for the unique biological function of small GTPase RHEB.
AB  - The small GTPase Rheb displays unique biological and biochemical properties
      different from other small GTPases and functions as an important mediator between
      the tumor suppressor proteins TSC1 and TSC2 and the mammalian target of rapamycin
      to stimulate cell growth. We report here the three-dimensional structures of
      human Rheb in complexes with GDP, GTP, and GppNHp (5'-(beta,gamma
      imide)triphosphate), which reveal novel structural features of Rheb and provide a
      molecular basis for its distinct properties. During GTP/GDP cycling, switch I of
      Rheb undergoes conformational change while switch II maintains a stable,
      unusually extended conformation, which is substantially different from the alpha
      helical conformation seen in other small GTPases. The unique switch II
      conformation results in a displacement of Gln64 (equivalent to the catalytic
      Gln61 of Ras), making it incapable of participating in GTP hydrolysis and thus
      accounting for the low intrinsic GTPase activity of Rheb. This rearrangement also
      creates space to accommodate the side chain of Arg15, avoiding its steric
      hindrance with the catalytic residue and explaining its noninvolvement in GTP
      hydrolysis. Unlike Ras, the phosphate moiety of GTP in Rheb is shielded by the
      conserved Tyr35 of switch I, leading to the closure of the GTP-binding site,
      which appears to prohibit the insertion of a potential arginine finger from its
      GTPase-activating protein. Taking the genetic, biochemical, biological, and
      structural data together, we propose that Rheb forms a new group of the Ras/Rap
      subfamily and uses a novel GTP hydrolysis mechanism that utilizes Asn1643 of the
      tuberous sclerosis complex 2 GTPase-activating protein domain instead of Gln64 of
      Rheb as the catalytic residue.

PMID- 15728575
TI  - Functional relevance of amino acid residues involved in interactions with ordered
      nucleic acid in a spherical virus.
AB  - In the spherical virion of the parvovirus minute virus of mice, several amino
      acid side chains of the capsid were previously found to be involved in
      interactions with the viral single-stranded DNA molecule. We have individually
      truncated by mutation to alanine many (ten) of these side chains and analyzed the
      effects on capsid assembly, stability and conformation, viral DNA encapsidation,
      and virion infectivity. Mutation of residues Tyr-270, Asp-273, or Asp-474 led to
      a drastic reduction in infectivity. Mutant Y270A was defective in capsid
      assembly; mutant D273A formed stable capsids, but it was essentially unable to
      encapsidate the viral DNA or to externalize the N terminus of the capsid protein
      VP2, a connected conformational event. Mutation of residues Asp-58, Trp-60, Asn
      183, Thr-267, or Lys-471 led to a moderate reduction in infectivity. None of
      these mutations had an effect on capsid assembly or stability, or on the DNA
      encapsidation process. However, those five mutant virions were substantially less
      stable than the parental virion in thermal inactivation assays. The results with
      this model spherical virus indicate that several capsid residues that are found
      to be involved in polar interactions or multiple hydrophobic contacts with the
      viral DNA molecule contribute to preserving the active conformation of the
      infectious viral particle. Their effect appears to be mediated by the non
      covalent interactions they establish with the viral DNA. In addition, at least
      one acidic residue at each DNA-binding region is needed for DNA packaging.

PMID- 15728576
TI  - Location and mobility of twin arginine translocase subunits in the Escherichia
      coli plasma membrane.
AB  - The twin arginine translocation (Tat) system transports folded proteins across
      the bacterial plasma membrane. Two primary Tat complexes have been identified,
      comprising TatABC or TatA multimers, which may interact at the point of
      translocation. We have analyzed green/cyan/yellow fluorescent protein (XFP)
      fusions to each of the Tat subunits. We show that the TatB and TatC fusions are
      active and incorporated into purified TatABC complexes. Proteolytic clipping of
      the TatA-XFP fusion precludes a definitive conclusion regarding activity, but we
      do find that the full fusion protein is preferentially incorporated into the
      TatABC complex. A previous study has proposed that TatB and possibly TatC are
      localized at the cell poles, whereas TatA is distributed more uniformly
      throughout the plasma membrane. Here, we likewise show that TatA-XFP is primarily
      distributed around the periphery of the cell. However, whereas much of the TatB
      XFP is found at the poles, quantitative imaging studies show that approximately
      half of the protein is uniformly distributed in the plasma membrane. Moreover, we
      show that the bulk of TatC-XFP is detected as a halo around the cells, in some
      cases as punctate areas that are much smaller than those occupied by TatB-green
      fluorescent protein (GFP), indicating a uniform distribution. No evidence for a
      polar localization of TatC-GFP was obtained. Although TatC-GFP is found correctly
      complexed with TatB, a high proportion of TatB-GFP is not linked to TatC, and we
      propose that this "free" TatB forms unphysiological assemblies, possibly because
      it is synthesized in excess. Since TatC is invariably complexed with TatB in wild
      type complexes, the combined data demonstrate that TatABC complexes are uniformly
      distributed throughout the plasma membrane. The significance of the punctate
      TatA/B/C-GFP is unclear; fluorescence recovery after photobleaching measurements
      show that these pools of proteins are immobile, whereas nonaggregated proteins
      are highly mobile in the plasma membrane.

PMID- 15728577
TI  - Dentin glycoprotein: the protein in the middle of the dentin sialophosphoprotein
      chimera.
AB  - Dentin sialophosphoprotein (DSPP) is a major secretory product of odontoblasts
      and is critical for proper dentin formation. DSPP is believed to be processed
      into only two structural/functional domains: dentin sialoprotein (DSP) and dentin
      phosphoprotein (DPP). Here we report the isolation and characterization of a
      third domain of DSPP, designated dentin glycoprotein (DGP). DGP was isolated from
      a guanidine/EDTA extract of porcine tooth dentin by ion exchange, hydroxyapatite
      affinity, size exclusion, and RP-HPL chromatography. Endoproteinase lysine C
      digestion products of DGP were characterized by Edman sequencing and mass
      spectrometry. The porcine DGP backbone is the 81-amino acid segment of DSPP
      (Ser392 to Gly472) between the DSP and DPP domains. DGP has four phosphorylated
      serine residues (Ser453, Ser455, Ser457, and Ser462) and one glycosylated
      asparagine (Asn397). There are no other post-translational modifications. DGP is
      a stains-all positive protein with an apparent molecular mass on SDS-PAGE of 19
      kDa, which is reduced by glycopeptidase A digestion to 16 kDa. A variety of
      glycans can be linked to Asn397. All are complex biantennary structures with a
      common N-linked pentasaccharide core (mannose3-N-acetylglucosamine2), most with a
      fucosyl residue on the innermost N-acetylglucosamine. The alpha1-3 and alpha1-6
      arms are always galactose beta1-4 N-acetylglucosamine beta1-2 mannose, and either
      or both arms can be unsialidated or monosialidated. The calculated monoisotopic
      molecular masses of the different glycosylated forms of the DGP phosphoprotein
      are: unsialidated 10,523 and 10,670, monosialidated 10,815 and 10,961, and
      disialidated 11,106, and 11,252 Da, with the disialidated forms being the most
      abundant.

PMID- 15728578
TI  - Identification of a DEF-type docking domain for extracellular signal-regulated
      kinases 1/2 that directs phosphorylation and turnover of the BH3-only protein
      BimEL.
AB  - The BH3-only protein, Bim, exists as three splice variants (Bim(S), Bim(L), and
      Bim(EL)) of differing pro-apoptotic potency. Bim(EL), the least effective killer,
      is degraded by the proteasome in response to phosphorylation by extracellular
      signal-regulated kinases 1 and 2 (ERK1/2). ERK1/2-dependent phosphorylation
      correlates with the presence of a domain unique to the Bim(EL) splice variant
      that includes the major ERK1/2 phosphorylation site Ser(65). However, efficient
      phosphorylation by ERK1/2, c-Jun N-terminal kinase, or p38 requires the presence
      in the substrate of a discrete kinase-docking domain as well as the
      phosphoacceptor site. Here we show that the region unique to Bim(EL) (amino acids
      41-97) harbors two potential DEF-type ERK1/2 kinase-docking domains, DEF1 and
      DEF2. Peptide competition assays revealed that the DEF2 peptide could act
      autonomously to bind active ERK1/2, whereas the DEF1 peptide did not. Truncation
      analysis identified a minimal region, residues 80-97, containing the DEF2 motif
      as sufficient for ERK1/2 binding. Mutation of key residues in the DEF2 motif
      abolished the interaction of ERK1/2 and Bim(EL) and also abolished ERK1/2
      dependent phosphorylation of Bim(EL) in vivo, thereby stabilizing the protein and
      enhancing cytotoxicity. Our results identify a new physiologically relevant
      functional motif in Bim(EL) that may account for the distinct biological
      properties of this splice variant.

PMID- 15728579
TI  - Gbetagamma-dependent and Gbetagamma-independent basal activity of G protein
      activated K+ channels.
AB  - Cardiac and neuronal G protein-activated K+ channels (GIRK; Kir3) open following
      the binding of Gbetagamma subunits, released from Gi/o proteins activated by
      neurotransmitters. GIRKs also possess basal activity contributing to the resting
      potential in neurons. It appears to depend largely on free Gbetagamma, but a
      Gbetagamma-independent component has also been envisaged. We investigated
      Gbetagamma dependence of the basal GIRK activity (A(GIRK,basal)) quantitatively,
      by titrated expression of Gbetagamma scavengers, in Xenopus oocytes expressing
      GIRK1/2 channels and muscarinic m2 receptors. The widely used Gbetagamma
      scavenger, myristoylated C terminus of beta-adrenergic kinase (m-cbetaARK),
      reduced A(GIRK,basal) by 70-80% and eliminated the acetylcholine-evoked current
      (I(ACh)). However, we found that m-cbetaARK directly binds to GIRK, complicating
      the interpretation of physiological data. Among several newly constructed
      Gbetagamma scavengers, phosducin with an added myristoylation signal (m
      phosducin) was most efficient in reducing GIRK currents. m-phosducin relocated to
      the membrane fraction and did not bind GIRK. Titrated expression of m-phosducin
      caused a reduction of A(GIRK,basal) by up to 90%. Expression of GIRK was
      accompanied by an increase in the level of Gbetagamma and Galpha in the plasma
      membrane, supporting the existence of preformed complexes of GIRK with G protein
      subunits. Increased expression of Gbetagamma and its constitutive association
      with GIRK may underlie the excessively high A(GIRK,basal) observed at high
      expression levels of GIRK. Only 10-15% of A(GIRK,basal) persisted upon expression
      of both m-phosducin and cbetaARK. These results demonstrate that a major part of
      Ibasal is Gbetagamma-dependent at all levels of channel expression, and only a
      small fraction (<10%) may be Gbetagamma-independent.

PMID- 15728580
TI  - Vanishingly low levels of Ess1 prolyl-isomerase activity are sufficient for
      growth in Saccharomyces cerevisiae.
AB  - Ess1 is an essential peptidylprolyl-cis/trans-isomerase in the yeast
      Saccharomyces cerevisiae. Ess1 and its human homolog, Pin1, bind to phospho-Ser
      Pro sites within proteins, including the carboxyl-terminal domain (CTD) of Rpb1,
      the largest subunit of RNA polymerase II (pol II). Ess1 and Pin1 are thought to
      control mRNA synthesis by catalyzing conformational changes in Rpb1 that affect
      interaction of cofactors with the pol II transcription complex. Here we have
      characterized wild-type and mutant Ess1 proteins in vitro and in vivo. We found
      that Ess1 preferentially binds and isomerizes CTD heptad-repeat (YSPTSPS)
      peptides that are phosphorylated on Ser5. Binding by the mutant proteins in vitro
      was essentially normal, and the proteins were largely stable in vivo. However,
      their catalytic activities were reduced >1,000-fold. These data along with
      results of in vivo titration experiments indicate that Ess1 isomerase activity is
      required for growth, but only at vanishingly low levels. We found that although
      wild-type cells contain about approximately 200,000 molecules of Ess1, a level of
      fewer than 400 molecules per cell is sufficient for growth. In contrast, higher
      levels of Ess1 were required for growth in the presence of certain metabolic
      inhibitors, suggesting that Ess1 is important for tolerance to environmental
      challenge.

PMID- 15728581
TI  - Crystal structure of human cystatin D, a cysteine peptidase inhibitor with
      restricted inhibition profile.
AB  - Cystatins are natural inhibitors of papain-like (family C1) and legumain-related
      (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted
      inhibitor found in human saliva and tear fluid. Compared with its homologues,
      cystatin D presents an unusual inhibition profile with a preferential inhibition
      cathepsin S > cathepsin H > cathepsin L and no inhibition of cathepsin B or pig
      legumain. To elucidate the structural reasons for this specificity, we have
      crystallized recombinant human Arg(26)-cystatin D and solved its structures at
      room temperature and at cryo conditions to 2.5- and 1.8-A resolution,
      respectively. Human cystatin D presents the typical cystatin fold, with a five
      stranded anti-parallel beta-sheet wrapped around a five-turn alpha-helix. The
      structures reveal differences in the peptidase-interacting regions when compared
      with other cystatins, providing plausible explanations for the restricted
      inhibitory specificity of cystatin D for some papain-like peptidases and its lack
      of reactivity toward legumain-related enzymes.

PMID- 15728582
TI  - Lower inhibitor development in hemophilia A mice following administration of
      recombinant factor VIII-O-phospho-L-serine complex.
AB  - Factor VIII is a multidomain protein composed of A1, A2, B, A3, C1, and C2
      domains. Deficiency or dysfunction of factor VIII causes hemophilia A, a bleeding
      disorder. Administration of exogenous recombinant factor VIII as a replacement
      leads to development of inhibitory antibodies against factor VIII in 15-30% of
      hemophilia A patients. Hence, less immunogenic preparations of factor VIII are
      highly desirable. Inhibitory antibodies against factor VIII are mainly directed
      against immunodominant epitopes in C2, A3, and A2 domains. Further, several
      universal epitopes for CD4+ T-cells have been identified within the C2 domain.
      The C2 domain is also known to interact specifically with phosphatidylserine-rich
      lipid vesicles. Here, we have investigated the hypothesis that complexation of O
      phospho-l-serine, the head group of phosphatidylserine, with the C2 domain can
      reduce the overall immunogenicity of factor VIII. The biophysical (circular
      dichroism and fluorescence) and biochemical studies (ELISA and size exclusion
      chromatography) showed that O-phospho-l-serine binds to the phospholipid-binding
      region in the C2 domain, and this interaction causes subtle changes in the
      tertiary structure of the protein. O-Phospho-l-serine also prevented aggregation
      of the protein under thermal stress. The immunogenicity of the factor VIII-O
      phospho-l-serine complex was evaluated in hemophilia A mice. The total and
      inhibitory antibody titers were lower for factor VIII-O-phospho-l-serine complex
      compared with factor VIII alone. Moreover, factor VIII administered as a complex
      with O-phospho-l-serine retained in vivo activity in hemophilia A mice. Our
      results suggest that factor VIII-O-phospho-l-serine complex may be beneficial to
      increase the physical stability and reduce immunogenicity of recombinant factor
      VIII preparations.

PMID- 15728583
TI  - Myocyte enhancer factor-2 and serum response factor binding elements regulate
      fast Myosin heavy chain transcription in vivo.
AB  - Adult fast muscle fibers express distinct myosin heavy chains (MyHC) in differing
      proportions, but the mechanisms underlying their differential expression remain
      undefined. We used a variety of in vitro and in vivo approaches to explore the
      contribution of transcriptional regulation to adult fast MyHC expression. Here we
      show that 800-1000 bp of a sequence upstream of the three mouse adult fast MyHC
      genes (Ia, IIb, and IId/x) are sufficient to drive muscle-specific and fiber
      specific expression in vivo. We show that the upstream promoter region of the
      gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains
      binding activity and transcriptional activation for three positive transcription
      factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas
      the other two genes (IIa and IId/x) have nucleotide substitutions in these sites
      that reduce binding and transcriptional activation. Finally, we demonstrate that
      regions upstream of 300 bp modulate the effects of these elements. Together,
      these data demonstrate that the quantitative differences in MyHC expression in
      mouse skeletal muscle have evolved at least in part through the elimination of
      positive-acting transcription factor binding sites.

PMID- 15728584
TI  - Two distinct head-tail interfaces cooperate to suppress activation of vinculin by
      talin.
AB  - Vinculin is autoinhibited by an intramolecular interaction that masks binding
      sites for talin and F-actin. Although a recent structural model explains
      autoinhibition solely in terms of the interaction between vinculin tail (Vt) and
      residues 1-258 (D1), we find an absolute requirement for an interface involving
      the D4 domain of head (Vh residues 710-836) and Vt. Charge-to-alanine mutations
      in Vt revealed a class of mutants, T12 and T19, distal to the V-(1-258) binding
      site, which showed increases in their Kd values for head binding of 100- and 42
      fold, respectively. Reciprocal mutation of residues in the D4 domain that contact
      Vt yielded a head-tail interaction mutant of comparable magnitude to T19. These
      findings account for the approximately 120-fold difference in Kd values between
      Vt binding to V-(1-258), as opposed to full-length Vh-(1-851). The significance
      of a bipartite autoinhibitory site is evidenced by its effects on talin binding
      to Vh. Whereas Vt fails to compete with the talin rod domain for binding to V-(1
      258), competition occurs readily with full-length Vh, and this requires the D4
      interface. Moreover in intact vinculin, mutations in the D4-Vt interface
      stabilize association of vinculin and talin rod. In cells, these head-tail
      interaction mutants induce hypertrophy and elongation of focal adhesions.
      Definition of a second autoinhibitory site, the D4-Vt interface, supports the
      competing model of vinculin activation that invokes cooperative action of ligands
      at two sites. Together the D1-Vt and D4-Vt interfaces provide the high affinity
      (approximately 10(-9)) autoinhibition observed in full-length vinculin.

PMID- 15728585
TI  - Mutations near amino end of alpha1(I) collagen cause combined osteogenesis
      imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide processing.
AB  - Patients with OI/EDS form a distinct subset of osteogenesis imperfecta (OI)
      patients. In addition to skeletal fragility, they have characteristics of Ehlers
      Danlos syndrome (EDS). We identified 7 children with types III or IV OI, plus
      severe large and small joint laxity and early progressive scoliosis. In each
      child with OI/EDS, we identified a mutation in the first 90 residues of the
      helical region of alpha1(I) collagen. These mutations prevent or delay removal of
      the procollagen N-propeptide by purified N-proteinase (ADAMTS-2) in vitro and in
      pericellular assays. The mutant pN-collagen which results is efficiently
      incorporated into matrix by cultured fibroblasts and osteoblasts and is
      prominently present in newly incorporated and immaturely cross-linked collagen.
      Dermal collagen fibrils have significantly reduced cross-sectional diameters,
      corroborating incorporation of pN-collagen into fibrils in vivo. Differential
      scanning calorimetry revealed that these mutant collagens are less stable than
      the corresponding procollagens, which is not seen with other type I collagen
      helical mutations. These mutations disrupt a distinct folding region of high
      thermal stability in the first 90 residues at the amino end of type I collagen
      and alter the secondary structure of the adjacent N-proteinase cleavage site.
      Thus, these OI/EDS collagen mutations are directly responsible for the bone
      fragility of OI and indirectly responsible for EDS symptoms, by interference with
      N-propeptide removal.

PMID- 15728586
TI  - Nuclear factor-kappaB activation leads to down-regulation of fatty acid oxidation
      during cardiac hypertrophy.
AB  - Little is known about the mechanisms responsible for the fall in fatty acid
      oxidation during the development of cardiac hypertrophy. We focused on the
      effects of nuclear factor (NF)-kappaB activation during cardiac hypertrophy on
      the activity of peroxisome proliferator-activated receptor (PPAR) beta/delta,
      which is the predominant PPAR subtype in cardiac cells and plays a prominent role
      in the regulation of cardiac lipid metabolism. Phenylephrine-induced cardiac
      hypertrophy in neonatal rat cardiomyocytes caused a reduction in the expression
      of pyruvate dehydrogenase kinase 4 (Pdk4), a target gene of PPARbeta/delta
      involved in fatty acid utilization, and a fall in palmitate oxidation that was
      reversed by NF-kappaB inhibitors. Lipopolysaccharide stimulation of NF-kappaB in
      embryonic rat heart-derived H9c2 myotubes, which only express PPARbeta/delta,
      caused both a reduction in Pdk4 expression and DNA binding activity of
      PPARbeta/delta to its response element, effects that were reversed by NF-kappaB
      inhibitors. Coimmunoprecipitation studies demonstrated that lipopolysaccharide
      strongly stimulated the physical interaction between the p65 subunit of NF-kappaB
      and PPARbeta/delta, providing an explanation for the reduced activity of
      PPARbeta/delta. Finally, we assessed whether this mechanism was present in vivo
      in pressure overload-induced cardiac hypertrophy. In hypertrophied hearts of
      banded rats the reduction in the expression of Pdk4 was accompanied by activation
      of NF-kappaB and enhanced interaction between p65 and PPARbeta/delta. These
      results indicate that NF-kappaB activation during cardiac hypertrophy down
      regulates PPARbeta/delta activity, leading to a fall in fatty acid oxidation,
      through a mechanism that involves enhanced protein-protein interaction between
      the p65 subunit of NF-kappaB and PPARbeta/delta.

PMID- 15728588
TI  - Evidence that dystroglycan is associated with dynamin and regulates endocytosis.
AB  - Disruption of the dystroglycan gene in humans and mice leads to muscular
      dystrophies and nervous system defects including malformation of the brain and
      defective synaptic transmission. To identify proteins that interact with
      dystroglycan in the brain we have used immunoaffinity purification followed by
      mass spectrometry (LC/MS-MS) and found that the GTPase dynamin 1 is a novel
      dystroglycan-associated protein. The beta-dystroglycan-dynamin 1 complex also
      included alpha-dystroglycan and Grb2. Overlay assays indicated that dynamin
      interacts directly with dystroglycan, and immunodepletion showed that only a pool
      of dynamin is associated with dystroglycan. Dystroglycan was associated and
      colocalized immunohistochemically with dynamin 1 in the central nervous system in
      the outer plexiform layer of retina where photoreceptor terminals are found.
      Endocytosis in neurons is both constitutive, as in non-neural cells, and
      regulated by neural activity. To assess the function of dystroglycan in the
      former, we have assayed transferrin uptake in fibroblastic cells differentiated
      from embryonic stem cells null for both dystroglycan alleles. In wild-type cells,
      dystroglycan formed a complex with dynamin and codistributed with cortactin at
      membrane ruffles, which are organelles implicated in endocytosis. Dystroglycan
      null cells had a significantly greater transferrin uptake, a process well known
      to require dynamin. Expression of dystroglycan in null cells by infection with an
      adenovirus containing dystroglycan reduced transferrin uptake to levels seen in
      wild-type embryonic stem cells. These data suggest that dystroglycan regulates
      endocytosis possibly as a result of its interaction with dynamin.

PMID- 15728587
TI  - The cytosolic phospholipase A2 pathway, a safeguard of beta2-adrenergic cardiac
      effects in rat.
AB  - We have recently demonstrated that in human heart, beta2-adrenergic receptors
      (beta2-ARs) are biochemically coupled not only to the classical adenylyl cyclase
      (AC) pathway but also to the cytosolic phospholipase A2 (cPLA2) pathway (Pavoine,
      C., Behforouz, N., Gauthier, C., Le Gouvello, S., Roudot-Thoraval, F., Martin, C.
      R., Pawlak, A., Feral, C., Defer, N., Houel, R., Magne, S., Amadou, A., Loisance,
      D., Duvaldestin, P., and Pecker, F. (2003) Mol. Pharmacol. 64, 1117-1125). In
      this study, using Fura-2-loaded cardiomyocytes isolated from adult rats, we
      showed that stimulation of beta2-ARs triggered an increase in the amplitude of
      electrically stimulated [Ca2+]i transients and contractions. This effect was
      abolished with the PKA inhibitor, H89, but greatly enhanced upon addition of the
      selective cPLA2 inhibitor, AACOCF3. The beta2-AR/cPLA2 inhibitory pathway
      involved G(i) and MSK1. Potentiation of beta2-AR/AC/PKA-induced Ca2+ responses by
      AACOCF3 did not rely on the enhancement of AC activity but was associated with
      eNOS phosphorylation (Ser1177) and L-NAME-sensitive NO production. This was
      correlated with PKA-dependent phosphorylation of PLB (Ser16). The constraint
      exerted by the beta2-AR/cPLA2 pathway on the beta2-AR/AC/PKA-induced Ca2+
      responses required integrity of caveolar structures and was impaired by Filipin
      III treatment. Immunoblot analyses demonstrated zinterol-induced translocation of
      cPLA and its cosedimentation with MSK1, eNOS, PLB, and sarcoplasmic reticulum
      Ca2+ pump (SERCA) 2a in a low density caveolin-3-enriched membrane fraction. This
      inferred the gathering of beta2-AR signaling effectors around
      caveolae/sarcoplasmic reticulum (SR) functional platforms. Taken together, these
      data highlight cPLA as a cardiac beta2-AR signaling pathway that limits beta2
      AR/AC/PKA-induced Ca2+ responses in adult rat cardiomyocytes through the
      impairment of eNOS activation and PLB phosphorylation.

PMID- 15728589
TI  - Pattern-based differential diagnosis in pulmonary vasculitis using volumetric CT.

PMID- 15728590
TI  - Chest radiograph scores as potential prognostic indicators in severe acute
      respiratory syndrome (SARS).
AB  - OBJECTIVE: We analyzed serial chest radiographic scores for lung opacification in
      patients with severe acute respiratory syndrome (SARS) for temporal changes and
      differences between fatal and discharged cases. We sought to establish the
      earliest radiographic scores sensitive as potential prognostic indicators of
      fatal outcomes. MATERIALS AND METHODS: Chest radiographs that had been obtained
      from presentation until the death or discharge of 313 patients with SARS were
      scored on the basis of the percentage area and location of lung opacification.
      Profile analysis and univariable logistic regression were performed on these
      radiographic scores. RESULTS: Despite the increased mortality risks of advanced
      age and male sex, no significant difference was seen in the percentage area of
      opacification (AO%) between the sexes in either the group of patients with fatal
      outcomes or the group of patients who were discharged. No difference existed
      between age groups (< 65 years vs >/= 65 years), except for the radiograph
      showing the peak lung opacification in the deceased group in which the lungs of
      older patients had less opacification than those of younger patients. The
      radiographic scores obtained by day 7 were the earliest ones with good
      performance in prognostic prediction. The model showed good discriminatory
      performance, indicated by high C-indexes for receiver operator characteristic
      curves (0.86 for AO% and 0.90 for the number of opacified zones). The predicted
      proportion of patients with fatal outcomes showed high agreement with percentage
      of patients who died (goodness-of-fit statistic p = 0.18 for AO%, 0.73 for the
      number of opacified zones). By day 7, crude odds ratio of death was 1.73 per 5%
      of AO% (p < 0.0001) or 2.93 per lung zone opacified (p < 0.0001). CONCLUSION:
      Chest radiographic scores (percentage of lung or the number of zones opacified)
      by day 7 could be used as fatal prognostic indicators.

PMID- 15728591
TI  - Radiation cost of helical high-resolution chest CT.
AB  - OBJECTIVE: In our department, most high-resolution CT (HRCT) scans of the lungs
      are performed in conjunction with a standard helical examination to assess the
      entire chest. This requires scanning the patient twice. The goal of this study
      was to determine if the radiation dose could be decreased by performing a single
      combination helical scan of the chest from which both 5-mm standard and 1.25-mm
      HRCT images could be obtained. CONCLUSION: Because the total measured radiation
      dose is 32% greater from a single combination helical HRCT scan of the chest
      versus separate standard helical plus axial HRCT scans, helical HRCT is not a
      clinically advisable technique.

PMID- 15728592
TI  - Direct detection of angioinvasive pulmonary aspergillosis in immunosuppressed
      patients: preliminary results with high-resolution 16-MDCT angiography.
AB  - OBJECTIVE: The aim of this study was to optimize detection of angioinvasive
      pulmonary aspergillosis by showing direct vessel involvement at a peripheral
      level with high-resolution MDCT angiography in patients with antibiotic-resistant
      fever of unknown origin under immunosuppression. Twelve CT angiographic
      examinations were prospectively performed in 10 patients with an optimized CT
      angiography protocol with 16-MDCT after IV administration of contrast agent using
      care bolus (Siemens Medical Solutions). Axial images and maximum intensity
      projections were evaluated for vascular occlusion by an experienced radiologist
      blinded to the clinical histories. Results were correlated with histology and
      clinical follow-up data including follow-up CT. Fourteen focal pulmonary lesions
      were detected by CT in eight patients. Eight of 14 lesions were confirmed by
      histology. In the remaining six lesions, diagnosis was made by clinical and CT
      follow-up. In nine of nine lesions in which angioinvasive infection was excluded,
      CT angiography showed patent vessels. In four of five lesions with histologically
      proven fungal angioinvasion, vascular occlusion was detected on CT angiography.
      CONCLUSION: High-resolution MDCT angiography has been shown to be a feasible
      technique to depict directly vessel occlusion in the setting of suspected fungal
      infections, especially for early diagnosis of angioinvasive pulmonary
      aspergillosis in immunosuppressed patients.

PMID- 15728593
TI  - Flat-panel display (LCD) versus high-resolution gray-scale display (CRT) for
      chest radiography: an observer preference study.
AB  - OBJECTIVE: Our objective was to compare cathode ray tube (CRT) display with
      liquid crystal display (LCD) for soft-copy viewing of chest radiographs in a
      clinical setting. MATERIALS AND METHODS: We displayed 80 posteroanterior digital
      chest radiographs side by side on a 5-megapixel CRT display and a 3-megapixel
      LCD. Gradation characteristics of both monitors were adjusted to DICOM display
      standards. Using a 4-point scale, seven radiologists ranked overall image quality
      and visibility of anatomic landmarks. Data analysis included Wilcoxon's rank sum
      test to assess the significance of preference for the different display modes and
      calculation of the percentage of images ranked equally by at least five of the
      seven radiologists. RESULTS: Wilcoxon's rank sum test found significant
      preferences (p < 0.001) for the CRT display for visualization of structures in
      low-attenuation areas of the thorax and for the LCD for visualization of
      structures in high-attenuation areas of the thorax. Overall image quality was
      ranked equal by at least five radiologists in 70% of cases, whereas for the
      remaining images a significant preference was found for the CRT display.
      CONCLUSION: We conclude that, under subdued ambient lighting conditions and
      without use of windowing, for most images the overall quality is equal with high
      resolution CRT display and LCD. In images judged preferentially, we found a
      significant superiority for LCD for delineating mediastinal structures and for
      CRT display for delineating structures in the lung.

PMID- 15728594
TI  - Pulmonary disease in patients with AIDS: high-resolution CT and pathologic
      findings.

PMID- 15728595
TI  - Assessment of left ventricular parameters using 16-MDCT and new software for
      endocardial and epicardial border delineation.
AB  - OBJECTIVE: The purpose of our study was to quantify left ventricular function and
      mass derived from retrospectively ECG-gated 16-MDCT coronary angiography data
      sets using a new analysis software based on automatic contour detection in
      comparison to corresponding standard of reference measurements acquired with MRI.
      SUBJECTS AND METHODS: Multiplanar reformations in the short-axis orientation were
      calculated from axial contrast-enhanced CT images in 18 patients (men, 15; women,
      three; age range, 38-70 years; mean, 57.4 +/- 10.2 [SD] years) who were referred
      for CT coronary angiography. End-diastolic volume (EDV), end-systolic volume
      (ESV), ejection fraction (EF), and left ventricular mass (LVM) were analyzed with
      a recently developed imaging software using an automated contour detection
      algorithm of left ventricular endo- and epicardial contours and by manual
      tracing. The data were compared with similar measurements on MRI as the standard
      of reference. RESULTS: EDV, ESV, EF, and LVM derived from an automated contour
      detection algorithm were not statistically significantly different from manual
      tracing (CT(auto) vs CT(manual): EDV = 137.1 +/- 45.7 mL vs 134.2 +/- 39.9 mL,
      ESV = 58.8 +/- 34.2 mL vs 58.1 +/-30.1 mL, EF = 59.2% +/- 13.7% vs 58.1% +/-
      12.0%, LVM = 130.9 +/- 29.1 g vs 133.7 +/- 33.2 g; p > 0.05). However, EDV (118.7
      +/- 43.6 mL), ESV (50.1 +/- 33.5 mL), and LVM (142.8 +/-38.4 g) as calculated on
      MR data sets were statistically significantly different from those calculated on
      CT (p < 0.05), whereas MRI-based EF (59.9% +/- 14.4%) did not differ
      statistically significantly from those based on both CT algorithms (p > 0.05).
      CONCLUSION: Automatic and manual analysis of data acquired during CT coronary
      angiography using a 16-MDCT scanner allows a reliable assessment of left
      ventricular ejection fraction and a rough estimation of left ventricular volumes
      and mass.

PMID- 15728596
TI  - Four-dimensional imaging of the heart based on near-isotropic MDCT data sets.

PMID- 15728597
TI  - Sonographic findings in ischemic colitis in 58 patients.
AB  - OBJECTIVE: The purpose of this study was to describe the sonographic findings of
      58 patients with proven ischemic colitis and to evaluate whether any of the
      findings are related to the presence or development of transmural necrosis.
      MATERIALS AND METHODS: We reviewed the histories of patients diagnosed with
      ischemic colitis over a period of 5.5 years. Sixty-two patients had undergone
      sonographic examinations. The spectrum of sonographic findings in ischemic
      colitis was based on the original imaging report, with an analysis of the
      presence of colonic abnormalities and their associated alterations. In the second
      part of the study, we divided the patients into two groups according to the
      presence or absence of transmural necrosis, and the sonographic findings of each
      group were compared. Ten patients had sonographic follow-up studies during their
      hospital stay. RESULTS: The prospective sensitivity of sonography for the
      characterization of colonic abnormalities was 93.5% (58/62 patients). Segmental
      involvement was detected in 57 of the 58 patients, with left-sided colitis in 47
      (81%). The mean length of bowel involved was 19 cm, with a mean wall thickness of
      7.6 mm. Colon wall stratification was preserved in 38 patients (66%). Altered
      pericolic fat was observed in 16 patients (28%). Absence of or barely visible
      color Doppler flow in the thickened bowel wall was recorded in 80% of patients.
      Altered pericolic fat was the only sonographic variable significantly associated
      with the presence of transmural necrosis (p = 0.004). Improvement as assessed on
      sonography was observed in all patients with a good clinical course. In patients
      with transmural necrosis, sonography did not show improvement. CONCLUSION:
      Sonography is a valuable technique for the detection of colonic abnormalities
      resulting from ischemic colitis. In this study, altered pericolic fat or the
      absence of improvement in sonographic follow-up studies were factors associated
      with transmural necrosis.

PMID- 15728598
TI  - Consensus on current clinical practice of virtual colonoscopy.
AB  - OBJECTIVE: The purpose of our study was to determine the current opinions
      regarding the performance, interpretation, reporting, and clinical role of
      virtual colonoscopy among a group of selected experts to develop a consensus
      statement. MATERIALS AND METHODS: A questionnaire was sent to 33 selected experts
      in virtual colonoscopy. Responses were tabulated and results were used to develop
      a consensus statement. The results of the questionnaire and consensus statement
      were sent to respondents for comment and approval. RESULTS: Thirty-one (93.9%) of
      33 surveys were returned. Eighty-seven percent (27/31) of respondents believe
      virtual colonoscopy is a credible screening method. Oral sodium phosphate
      solution is the laxative preferred by more than 66% (18/27), whereas 62% (13/21)
      do not believe fecal tagging is necessary. All respondents (25/25) think that
      both prone and supine imaging is required, with most (81%, 21/26) believing IV
      contrast material is not necessary. The routine use of spasmolytics is suggested
      by only 15% (4/26). The largest acceptable slice thickness of 3 mm is agreed on
      by 88% (22/25). All respondents believe screening virtual colonoscopy should be
      performed at a lower dose per slice than conventional CT. Most (80%, 20/25)
      believe the optimum method of interpreting virtual colonoscopy should be primary
      axial review, with 3D used for problem solving. All but one respondent (96%,
      26/27) agree there is a threshold size below which polyps are not clinically
      important. When reporting virtual colonoscopy results, 59% (16/27) believe polyps
      less than 4 mm need not be reported. CONCLUSION: A consensus is developing among
      experts as to the appropriate manner in which virtual colonoscopy should be
      performed, interpreted, and reported.

PMID- 15728599
TI  - Pharyngeal retention cysts: radiographic findings in seven patients.
AB  - OBJECTIVE: The purpose of this study was to better characterize the radiographic
      features of pharyngeal retention cysts on double-contrast pharyngograms.
      CONCLUSION: Pharyngeal retention cysts typically involve the valleculae,
      appearing on double-contrast pharyngograms as small, round or ovoid, well
      circumscribed, smooth-surfaced submucosal masses that are best visualized on
      frontal views of the pharynx. Such features should be highly suggestive of benign
      retention cysts, obviating further diagnostic workup in asymptomatic patients.
      When the cysts are lobulated or completely obliterate the valleculae, however,
      further evaluation by otolaryngologic examination may be required to rule out
      malignant tumor in the pharynx.

PMID- 15728600
TI  - Gastrointestinal schwannomas: CT features with clinicopathologic correlation.
AB  - OBJECTIVE: The objective of this study was to describe the CT features of
      gastrointestinal schwannomas with clinicopathologic correlation. CONCLUSION:
      Gastrointestinal schwannomas are uncommon mesenchymal neoplasms that are uniquely
      different tumors from their soft-tissue and central nervous system counterparts.
      They are homogeneously attenuating, well-defined, mural masses on CT. The lack of
      low-attenuation hemorrhage, necrosis, and degeneration within the tumor may help
      distinguish these tumors from gastrointestinal stromal tumors on CT.

PMID- 15728601
TI  - Gastrointestinal stromal tumors: clinical, radiologic, and pathologic features.

PMID- 15728602
TI  - Biliary complications after liver transplantation: diagnosis with MR
      cholangiopancreatography.
AB  - OBJECTIVE: We sought to evaluate MR cholangiopancreatography (MRCP) as the only
      imaging procedure used in the diagnosis and management of biliary complications
      after orthotopic liver transplantation (OLT). CONCLUSION: MRCP is a useful
      imaging procedure in the assessment of biliary complications after OLT.

PMID- 15728603
TI  - Contrast-enhanced sonography with SonoVue: enhancement patterns of benign focal
      liver lesions and correlation with dynamic gadobenate dimeglumine-enhanced MRI.
AB  - OBJECTIVE: Contrast-enhanced real-time low-mechanical-index sonography is a new
      diagnostic technique for the assessment of macro- and microcirculation. The
      purpose of our article is to describe contrast-enhancement patterns of different
      benign focal liver lesions using the second-generation contrast agent SonoVue and
      to compare these findings with those of gadobenate dimeglumine-enhanced MRI.
      CONCLUSION: SonoVue-enhanced real-time low-mechanical-index sonography provides
      specific contrast-enhancement patterns of different benign focal liver lesions,
      allowing accurate characterization. Findings on SonoVue-enhanced sonography
      correlate well with those obtained on gadobenate dimeglumine-enhanced MRI.

PMID- 15728604
TI  - Successful treatment of hepatocellular adenoma with percutaneous radiofrequency
      ablation.
AB  - OBJECTIVE: The purpose of our study was to report the safe and successful
      treatment of hepatocellular adenoma with percutaneous radiofrequency ablation.
      CONCLUSION: Our limited experience indicates that percutaneous radiofrequency
      ablation is both safe and effective in the treatment of the small hepatocellular
      adenoma in carefully selected patients.

PMID- 15728605
TI  - Expression of vascular endothelial growth factor in hepatocellular carcinoma and
      the surrounding liver and correlation with MRI findings.
AB  - OBJECTIVE: The purpose of our study was to assess the correlation between the
      quantitative and qualitative imaging findings on unenhanced and gadolinium
      enhanced MR images and the intensity of vascular endothelial growth factor (VEGF)
      expression in hepatocellular carcinomas and in the surrounding nontumorous liver.
      MATERIALS AND METHODS: The intensities of VEGF expression in hepatocellular
      carcinoma and in the surrounding liver by Western blot analysis were converted to
      VEGF expression indexes (VEGF(IND)) in 22 surgical specimens ranging in size from
      14 to 126 mm (mean, 47.6 +/- 29.5 mm) that were resected in 22 patients (17 men
      and five women; age range, 41-85 years [mean, 64 years]) between April 2000 and
      October 2002. MR images were retrospectively evaluated to determine contrast-to
      noise ratios (CNRs), signal intensity SD ratios, and phase-shift indexes. Signal
      intensity characteristics of hepatocellular carcinomas were reviewed
      independently by two experienced radiologists who were unaware of the pathologic
      diagnosis or the results of immunoblotting. CNRs, SD ratios, and phase-shift
      indexes were correlated with VEGF(IND) using a simple regression test, and signal
      intensity characteristics were correlated with VEGF(IND) using the Spearman's
      rank correlation test. RESULTS: On opposed-phase T1-weighted spoiled gradient
      recalled echo (GRE) images, CNRs correlated inversely with the VEGF(IND) of
      hepatocellular carcinomas (r = -0.46, p = 0.038). CNRs on T2-weighted fast spin
      echo images correlated directly with the VEGF(IND) of hepatocellular carcinomas
      (r = 0.49, p = 0.025), and on gadolinium-enhanced hepatic arterial phase GRE
      images marginally and inversely correlated with VEGF(IND) (r = -0.39, p = 0.081).
      On T2-weighted fast spin-echo images, SD ratios correlated directly with the
      VEGF(IND) of hepatocellular carcinomas (r = 0.44, p = 0.044). No correlation was
      found between phase-shift indexes and VEGF expression. The qualitatively assessed
      signal intensity heterogeneities of hepatocellular carcinomas correlated directly
      with the VEGF(IND) of hepatocellular carcinomas on opposed-phase T1-weighted GRE,
      T2-weighted fast spin-echo, hepatic arterial phase GRE, and equilibrium phase GRE
      images. CONCLUSION: Our results indicate that the signal intensity and
      heterogeneity of hepatocellular carcinomas on MR images correlate with the degree
      of VEGF expression in hepatocellular carcinomas.

PMID- 15728606
TI  - Utility of breath-hold fast-recovery fast spin-echo t2 versus respiratory
      triggered fast spin-echo T2 in clinical hepatic imaging.
AB  - OBJECTIVE: The objective of our study was to compare a breath-hold fat-suppressed
      fast-recovery fast spin-echo (FSE) T2-weighted sequence with a respiratory
      triggered fat-suppressed FSE T2-weighted sequence to assess the effect on image
      quality and lesion detection and characterization in clinical hepatic imaging.
      MATERIALS AND METHODS: Both the breath-hold fat-suppressed fast-recovery FSE and
      respiratory-triggered fat-suppressed FSE T2-weighted sequences were acquired in
      46 patients. Two radiologists, blinded to clinical data, independently evaluated
      randomized images from both sequences. Qualitatively, images were graded on a 5
      point scale for five different characteristics. The number and location of
      lesions were recorded. The confidence of detection and the confidence of
      characterization (solid vs nonsolid) were graded on a 5-point scale. A consensus
      review using radiology, clinical, and pathology data served as the standard.
      Receiver operating characteristic (ROC) curve analysis (area under the ROC curve
      [A(z)]) was used to compare each reviewer's interpretation against the consensus
      interpretation. Quantitative analysis was performed by calculating the liver
      signal-to-noise ratio (SNR), liver-to-spleen contrast-to-noise ratio (CNR), and
      lesion-to-liver CNR. Both one- and two-tailed Student's t tests were used to
      check for significance. RESULTS: Qualitatively, both reviewers graded the breath
      hold fat-suppressed fast-recovery FSE T2-weighted sequence better than the
      respiratory-triggered fat-suppressed FSE T2-weighted sequence on all five
      characteristics (p < 0.005). Of 78 lesions detected, 29 were characterized as
      solid; 47, nonsolid; and two, indeterminate. On ROC analysis, there were no
      significant differences between the breath-hold fat-suppressed fast-recovery FSE
      and respiratory-triggered fat-suppressed FSE T2-weighted sequences in lesion
      detection (A(z) reviewer 1, 0.77 and 0.83, respectively, [p = 0.12]; A(z)
      reviewer 2, 0.84 and 0.80, respectively [p = 0.12]) or in lesion characterization
      (A(z) reviewer 1, 0.86 and 0.92, respectively [p = 0.33]; A(z) reviewer 2, 0.90
      and 0.91, respectively [p = 0.79]). Quantitatively, liver SNRs, spleen CNRs, and
      lesion CNRs (solid and nonsolid lesions) were significantly better on the breath
      hold fat-suppressed fast-recovery FSE T2-weighted images than on the respiratory
      triggered fat-suppressed FSE T2-weighted images (p < 0.005). CONCLUSION: Breath
      hold fat-suppressed fast-recovery FSE T2-weighted images were of better quality
      than respiratory-triggered fat-suppressed FSE T2-weighted images, and lesion
      detection and characterization were comparable.

PMID- 15728607
TI  - MDCT of abdominal wall hernias: is there a role for valsalva's maneuver?
AB  - OBJECTIVE: Our objective was to evaluate the role of Valsalva's maneuver during
      MDCT for the diagnosis and characterization of abdominal wall hernias. SUBJECTS
      AND METHODS: From September 2002 to May 2003, 100 consecutive patients (37 men
      and 63 women; mean age, 53 years) with suspected anterior abdominal wall hernias
      underwent 4-, 8-, or 16-MDCT with and without Valsalva's maneuver. Patients
      received both oral and IV contrast material. On a workstation, three independent
      reviewers evaluated each scan obtained during rest and during Valsalva's maneuver
      for the following parameters: anteroposterior (AP) diameter of the abdomen;
      presence, location, and contents of the hernia; and transverse diameter of the
      fascial defect. The scans were compared to assess for changes in hernia size and
      contents and to determine whether the hernia would have been overlooked without
      Valsalva's maneuver. Fisher's exact test, the McNemar test, and Cohen's kappa
      coefficient were used to assess for significant differences. RESULTS: The three
      reviewers identified a mean of 72 abdominal wall hernias (72%). The reviewers
      agreed (kappa = 0.723) with respect to the presence of a hernia. AP diameters
      increased an average of 1.33 cm during Valsalva's maneuver (p < 0.001). The
      transverse diameter of the fascial defect increased an average of 0.66 cm and the
      AP diameter of the hernia sac increased an average of 0.79 cm during Valsalva's
      maneuver (p < 0.001). Fifty percent of the hernias became more apparent with
      Valsalva's maneuver. Ten percent of the hernias could be detected only on the
      scan obtained during Valsalva's maneuver. Conversely, in no patients was the
      hernia detected only on the rest scan. CONCLUSION: As opposed to scans obtained
      at rest, scans obtained during Valsalva's maneuver aid in the detection and
      characterization of suspected abdominal wall hernias. A single scan obtained
      during Valsalva's maneuver is sufficient to detect 100% of anterior abdominal
      wall hernias identified on CT.

PMID- 15728608
TI  - 3D pancreatic arteriography with MDCT during intraarterial infusion of contrast
      material in the detection and localization of insulinomas.

PMID- 15728609
TI  - Why we miss the diagnosis of appendicitis on abdominal CT: evaluation of imaging
      features of appendicitis incorrectly diagnosed on CT.
AB  - OBJECTIVE: Our purpose was to retrospectively evaluate the cases of patients with
      surgically proven appendicitis that was misdiagnosed on abdominal CT to determine
      the causes of the missed diagnosis. CONCLUSION: Increased awareness of the
      underlying factors common to most cases of the missed diagnosis of appendicitis
      on CT and increased radiologic vigilance in cases of atypical abdominal pain may
      enable us to further improve our diagnostic accuracy.

PMID- 15728610
TI  - MRI of adrenal and extraadrenal pheochromocytoma.

PMID- 15728611
TI  - Prospective comparison of mammography, sonography, and MRI in patients undergoing
      neoadjuvant chemotherapy for palpable breast cancer.
AB  - OBJECTIVE: The objective of our study was to determine the relative accuracy of
      mammography, sonography, and MRI in predicting residual tumor after neoadjuvant
      chemotherapy for breast cancer as compared with the gold standards of physical
      examination and pathology. SUBJECTS AND METHODS: Forty-one women with stage IIB
      III palpable breast cancer were prospectively enrolled in a study investigating
      the effects of sequential single-agent chemotherapy (doxorubicin followed by
      paclitaxel or vice versa) on tumor imaging. The study cohort consisted of the
      first 31 patients (age range, 31-65 years; mean, 45 years) who completed the
      protocol. All underwent physical examination, mammography, sonography, and MRI
      before and after receiving each neoadjuvant chemotherapeutic drug. Imaging
      studies were reviewed by two radiologists using conventional lexicons for lesion
      analysis, and the findings were compared with clinical response and pathology
      results. RESULTS: Complete, partial, and stable clinical response as defined by
      clinical examination was seen in 15, 14, and two of the 31 patients,
      respectively. Agreement rates about the degree of response were 32%, 48%, and
      55%, respectively, for mammography, sonography, and MRI compared with clinical
      evaluation and did not differ statistically. Agreement about the rate of response
      as measured by clinical examination, mammography, sonography, and MRI compared
      with the gold standard (pathology) was 19%, 26%, 35%, and 71%, respectively. Of
      the four, MRI agreed with the gold standard significantly more often (p < 0.002
      for all three paired comparisons with MRI). When there was disagreement with the
      gold standard, none of the four exhibited a significant tendency to either under-
      or overestimate. CONCLUSION: MRI appears to provide the best correlation with
      pathology-better than physical examination, mammography, and sonography-in
      patients undergoing neoadjuvant chemotherapy. However, MRI may overestimate (6%)
      or underestimate (23%) residual disease in approximately 29% of the patients (95%
      confidence interval, 14-48%).

PMID- 15728612
TI  - Assessment of suspected breast cancer by MRI: a prospective clinical trial using
      a combined kinetic and morphologic analysis.
AB  - OBJECTIVE: The objective of our study was to assess the incremental value of
      contrast-enhanced MRI in the diagnosis and treatment planning using both a three
      time point kinetic and morphologic analysis in addition to mammography and
      sonography in patients thought to have early-stage breast cancer. SUBJECTS AND
      METHODS: Contrast-enhanced bilateral breast MRI was performed prospectively on 65
      patients with highly suspicious imaging findings (BI-RADS category 4 or 5). All
      enrolled patients were believed to be candidates for breast conservation on the
      basis of clinical examination, mammography, and sonography. The primary index
      lesion's characteristics, size, and extent were assessed. Also, additional
      lesions detected by MRI that could represent potential malignancies in both the
      ipsilateral and contralateral breast were evaluated. Morphologic assessment and
      kinetic analysis were performed on each lesion using dedicated postprocessing and
      display software. The patients were reevaluated as to whether they were still
      candidates for breast-conservation therapy after the MRI examination and
      subsequent biopsies. RESULTS: There were 46 patients (71%) whose primary breast
      lesion (detected by mammography, sonography, or both) was found to be malignant
      (39 invasive breast cancers, five intraductal cancers, and two lymphomas). For
      the primary index lesions, the sensitivity for MRI was 100% (44/44) for
      predicting a breast malignancy and the specificity was 73.7% (14/19) for
      predicting benign lesions. MRI detected an additional 37 lesions, of which 23
      were cancerous, beyond those suspected on mammography or sonography. One or more
      additional ipsilateral breast cancers were detected in 32% (14/44) of breast
      cancer patients and contralateral breast cancers in 9% (4/44) of the breast
      cancer patients. MRI also resulted in an incremental recommendation of mastectomy
      in 18% (8/44) of the pathologically confirmed breast cancer patients. MRI
      resulted in additional biopsy of only 14 benign lesions, six of which were shown
      to be atypical ductal hyperplasia. CONCLUSION: When added to the standard
      evaluation of clinical examination, mammography, and sonography in patients
      thought to have early-stage breast cancer, contrast-enhanced MRI using both a
      kinetic and morphologic analysis will often result in changes in recommended
      patient management and better treatment planning and will result in no
      significant increase in biopsies of benign lesions. In addition, there is a
      significant detection rate of occult contralateral breast cancers.

PMID- 15728613
TI  - Computer-aided detection of amorphous calcifications.
AB  - OBJECTIVE: Computer-aided detection (CAD) systems have been used successfully to
      detect malignant calcifications on mammography, with sensitivities ranging from
      86% to 99%. Amorphous calcifications are a subset of small indistinct
      calcifications of intermediate concern that have a 20% likelihood of being
      malignant and that are frequently overlooked on mammography. The purpose of our
      study was to determine the sensitivity of one commercially available CAD system
      for detecting amorphous calcifications. MATERIALS AND METHODS: A commercially
      available CAD system evaluated mammograms of 82 patients with 85 mammographically
      detected and histologically sampled groups of amorphous calcifications (21
      malignant, 14 high risk, and 50 benign). The sensitivity of the system for
      detecting the calcifications on at least one image of the two-view mammographic
      examination (case sensitivity) and on each individual mammographic image (image
      sensitivity) was determined. Findings were correlated with results from large
      core needle biopsy or surgical excision in each case. RESULTS: The CAD system
      detected amorphous calcifications in 43 of 85 cases (case sensitivity, 51%) and
      in 59 of 146 mammographic images (image sensitivity, 40%). The case sensitivities
      by histologic outcome were 57% for malignant calcifications, 29% for high-risk
      calcifications, and 54% for benign calcifications. An average of 2.0 false
      positive marks were displayed per case. CONCLUSION: The CAD sensitivity for
      malignant amorphous calcifications is markedly lower than previously reported for
      all malignant calcifications. Breast imaging radiologists who use CAD systems
      should continue to search diligently for these difficult-to-detect lesions.

PMID- 15728614
TI  - A computer-aided detection system for the evaluation of breast cancer by
      mammographic appearance and lesion size.
AB  - OBJECTIVE: The purpose of our study was to evaluate the performance of a computer
      aided detection (CAD) system in the detection of breast cancer based on
      mammographic appearance and lesion size. CONCLUSION: The CAD system correctly
      marked most biopsy-proven breast cancers, with a greater sensitivity for
      microcalcification than for mass lesions but with no significant difference in
      performance based on cancer size. CAD was highly effective in detecting even the
      smallest lesions, with a sensitivity of 92% for lesions of 5 mm or less. CAD is a
      useful tool for the detection of breast cancer.

PMID- 15728616
TI  - Percutaneous femoral catheter placement for long-term chemotherapy infusions:
      preliminary technical results.
AB  - OBJECTIVE: The purpose of our study was to evaluate the feasibility and
      usefulness of using a port-catheter system equipped with a W-spiral catheter for
      hepatic chemotherapy; this novel catheter does not require fixation by
      pericatheter embolization and can be safely withdrawn when not needed. SUBJECTS
      AND METHODS: Sixty-one patients (40 men and 2l women; mean age, 59 years) with
      advanced liver cancers (primary hepatic or biliary cancer [n = 31] and metastatic
      liver cancer [n = 30]) underwent percutaneous port-catheter placement with the
      tip of W-spiral catheter inserted into the right gastroepiploic artery and the
      side-hole opened at the common hepatic artery after embolization of the right
      gastric artery, pancreaticoduodenal arteries, or aberrant hepatic arteries.
      Pericatheter embolization for preventing catheter dislodgement was not performed.
      The technical success of port-catheter placement, clinical patency of the port
      catheter system, and technical success of port-catheter removal were evaluated.
      RESULTS: Percutaneous port-catheter placement using this method was successfully
      performed in 59 (97%) of 61 patients. Subsequently, chemotherapy was successfully
      performed through the port in 57 (93%) of 61 patients. Complications during and
      after the procedure were observed in two (3%) of 61 patients and 12 (20.7%) of 58
      patients. Hepatic artery thrombosis occurred in two (3.4%) of 58 patients. The
      port-catheter removal and the catheter replacement were performed in eight and
      four patients, respectively, who wanted the procedure. It was completed
      successfully without any complications. CONCLUSION: This method of implantation
      of a port-catheter system appeared to offer clinical advantages of safe catheter
      removal, femoral artery access, and an acceptable complication rate.

PMID- 15728615
TI  - Comparison of renal ablation with monopolar radiofrequency and hypertonic-saline
      augmented bipolar radiofrequency: in vitro and in vivo experimental studies.
AB  - OBJECTIVE: We sought to determine whether hypertonic-saline (HS)-augmented
      bipolar radiofrequency ablation has advantages over monopolar radiofrequency
      ablation for creating larger areas of coagulation necrosis in the kidney.
      MATERIALS AND METHODS: Using a 200-W generator and bipolar perfused-cooled
      electrodes or a monopolar cooled-tip electrode, we performed 14 radiofrequency
      ablations in explanted bovine kidneys. Radiofrequency was applied in standard
      monopolar (n = 7) or bipolar (n = 7) modes at 100 W for 10 min. In the bipolar
      mode, the perfused-cooled electrodes were placed at interelectrode distances of 3
      cm, and a 6% sodium chloride solution was instilled into tissue at a rate of 2
      mL/min through the electrodes. For in vivo experiments, either monopolar (n = 7)
      or HS-augmented bipolar (n = 7) radiofrequency ablation was performed in the
      lower pole of canine kidneys. Three days after the procedure, contrast-enhanced
      CT scans were obtained to evaluate the volumes of the ablation regions, and the
      kidneys were harvested for gross measurements. Technical parameters such as
      changes in impedance and current during radiofrequency ablation and dimensions of
      the thermal ablation zones were compared between the two groups. RESULTS: In ex
      vivo and in vivo experiments, the frequency of the pulsed radiofrequency
      application caused by rises in impedance was higher in the monopolar mode than in
      the bipolar mode during the application of radiofrequency energy. The in vivo
      study showed that the bipolar radiofrequency ablation allowed larger mean current
      flows than the monopolar radiofrequency ablation (i.e., mean +/- SD, 1,654 +/-
      144 mA vs 967 +/- 597 mA) (p < 0.05). Ex vivo studies revealed that the volumes
      of bipolar radiofrequency-induced ablation regions were substantially larger than
      those of monopolar radiofrequency-induced ablation regions (26.1 +/- 10.5 cm(3)
      vs 10.2 +/- 4.2 cm(3)). In vivo studies showed bipolar radiofrequency ablation
      achieved larger coagulation necrosis than monopolar radiofrequency (3.2 +/- 0.3
      cm vs 2.4 +/-0.4 cm) (p < 0.05). This was confirmed by the measured volume of
      nonenhancing area on contrast-enhanced CT (20.4 +/- 6.4 cm(3) vs 13.5 +/- 6.0
      cm(3)). CONCLUSION: HS-augmented bipolar radiofrequency ablation using perfused
      cooled electrodes shows better performance in creating coagulation necrosis than
      monopolar radiofrequency ablation in the kidney of an animal model.

PMID- 15728617
TI  - Gas distribution in intraabdominal and pelvic abscesses on CT is associated with
      drainability.
AB  - OBJECTIVE: Intraabdominal and pelvic abscesses are treated by percutaneous image
      guided drainage, under sedation or general anesthesia. This study attempts to
      determine if the CT features of gas distribution are associated with
      "drainability." Our premise was that gas may be trapped deep in a collection as
      bubbles, if the material is thick. Gas may rise to the surface if the material is
      thin, forming either an air-fluid level or superficial bubbles. MATERIALS AND
      METHODS: Patients with intraabdominal and pelvic abscesses were identified by the
      interventional radiology database, after research ethics board approval. Patients
      without prior CT were excluded. The imaging and clinical records were analyzed
      retrospectively. Intracollection gas distribution was recorded as superficial
      bubbles, deep bubbles, or air-fluid levels. Collections were classified
      accordingly: type 1, air-fluid levels; type 2, superficial or deep bubbles and
      air-fluid levels; type 3, superficial bubbles; type 4, deep bubbles; and type 5,
      no gas. RESULTS: One hundred five abscesses were examined in 61 patients, ranging
      in age from 2-17 years. Eight of 8 of type 1, 16 of 16 of type 2, 19 of 21 of
      type 3, 8 of 13 of type 4, and 43 of 47 of type 5 were drainable. The abscesses
      of all patients with an air-fluid level were drainable. Of abscesses with deep
      bubbles, 61.5% were drainable, versus 90.5% of those with superficial bubbles. Of
      those with superficial gas (superficial bubbles or air-fluid levels), 95.6% were
      drainable. In comparison with superficial gas, abscesses with deep trapped gas
      were associated with a longer duration of drainage, longer hospital stay, lower
      percentage of successful drainage, and higher percentage of residual collections.
      The difference is significant for drainability (p = 0.0048; p = 0.0331 after
      statistical adjustment for multiple testing). CONCLUSION: Distribution of gas in
      an intraabdominal or pelvic abscess is associated with drainability. Abscesses
      with superficial gas (superficial bubbles or air-fluid levels) have a greater
      chance of being drained successfully than do abscesses with deep trapped gas.

PMID- 15728618
TI  - Transjugular intrahepatic portosystemic shunt placement in liver transplant
      recipients: experiences with pediatric and adult patients.
AB  - OBJECTIVE: The purpose of our study was to evaluate the safety and efficacy of
      transjugular intrahepatic portosystemic shunts (TIPS) in pediatric and adult
      liver transplant recipients. A retrospective review of six TIPS placed in six
      liver transplant recipients-a pediatric patient with a split liver transplant, a
      pediatric patient with left lateral segment transplant, and four adult patients
      was performed. CONCLUSION: TIPS placement in both pediatric and adult liver
      transplant recipients is feasible. In liver transplant patients who are
      recipients of a left lateral segment or a split liver transplant, knowledge of
      the liver transplant anatomy is critical in the placement of TIPS. TIPS placement
      is a treatment option and a bridge to retransplantation for patients who have
      undergone liver transplantation and develop sequelae of portal hypertension.

PMID- 15728619
TI  - Percutaneous cryoablation of symptomatic extraabdominal metastatic disease:
      preliminary results.
AB  - OBJECTIVE: The objective of our study was to describe our initial experience
      using percutaneous cryoablation for palliation of symptomatic extraabdominal
      metastases or recurrent soft-tissue tumors. CONCLUSION: Preliminary results
      suggest that percutaneous cryoablation may offer a minimally invasive alternative
      for relief of symptomatic metastatic disease in patients for whom conventional
      therapy failed.

PMID- 15728621
TI  - Diagnostic accuracy of time-resolved 2D projection MR angiography for symptomatic
      infrapopliteal arterial occlusive disease.
AB  - OBJECTIVE: Our objective was to evaluate the diagnostic accuracy of time-resolved
      2D projection MR angiography in detecting calf and pedal artery occlusive
      disease. MATERIALS AND METHODS: Time-resolved MR angiography of calf and pedal
      arteries was performed on 59 symptomatic legs of 52 patients using the head coil
      and bolus injections of 6 mL of gadolinium contrast medium. Selective X-ray
      digital subtraction angiography was performed within 30 days after MR
      angiography. Calf and pedal arteries were divided into 10 segments. X-ray digital
      subtraction angiography and MR angiography images were retrospectively
      interpreted by three expert observers, who graded segments as having no
      significant stenosis, significant stenosis (> 50%), or occlusion. The accuracy of
      MR angiography interpretations was compared with the accuracy of consensus X-ray
      digital subtraction angiography interpretations as the standard of reference.
      Arterial segments with discrepant grading on X-ray digital subtraction
      angiography and MR angiography were reviewed again to determine the reasons for
      disagreement. RESULTS: Arterial phase MR angiography images free of venous
      contamination were obtained in every case. The agreement between MR angiography
      and X-ray digital subtraction angiography in depicting infrapopliteal arterial
      disease was fair to good (kappa = 0.44-0.92). Overall sensitivity and specificity
      were 83% and 87%, respectively, for detecting significant stenosis of calf and
      pedal arteries and 86% and 93%, respectively, for detecting occlusions. Accuracy
      was higher in the larger vessels-for example, calf (84%) compared with foot
      (71%). In 21% (22/105) of the segments graded differently on MR angiography than
      on X-ray digital subtraction angiography, it was believed that MR angiography was
      more likely to be correct than X-ray digital subtraction angiography because of
      visualization of late-filling arteries on MR angiography that did not opacify on
      X-ray digital subtraction angiography. CONCLUSION: Time-resolved 2D projection MR
      angiography accurately evaluates calf and pedal arteries without degradation from
      venous contamination.

PMID- 15728620
TI  - Diagnosis and treatment of renovascular hypertension: a cost-benefit analysis.
AB  - OBJECTIVE: We sought to evaluate and compare the relative cost-benefit of Doppler
      sonography, MR angiography, and captopril-enhanced renal scintigraphy as
      techniques for predicting a patient's clinical response to renal angioplasty.
      MATERIALS AND METHODS: Estimations of positive and negative predictive values of
      baseline and captopril-enhanced renal scintigraphy and Doppler sonography
      examinations for predicting a favorable outcome after renal angioplasty were
      based on a previously published prospective study involving 74 patients who
      underwent this treatment. For gadolinium-enhanced MR angiography, predictive
      values were calculated from a subpopulation of 57 of these 74 subjects. The value
      of different combined strategies with these techniques for predicting clinical
      success after angioplasty was evaluated in this population. The costs of
      investigation and treatment per improved patient were calculated for each imaging
      technique and for combined strategies in a hypothetic 1,000-patient population
      with a 30% prevalence of renal artery stenosis, relying on the diagnostic
      performance reported in the literature for each technique in detecting renal
      artery stenosis. RESULTS: The costs for each improved patient were $12,579 for
      patients selected on the basis of a positive finding on Doppler sonography (false
      negative results = 12/1,000) and $10,149 for patients selected with criteria
      combining a positive finding on Doppler sonography with a bilateral resistive
      index of less than 0.75 (false-negative results = 32/1,000). Patient selection
      based on a positive finding on MR angiography cost $18,119 (false-negative
      results = 0), whereas the cost of patient selection based on a positive finding
      on renal scintigraphy was $12,939 (false-negative results = 29/1,000).
      CONCLUSION: Doppler sonography is more cost-efficient but less sensitive than MR
      angiography for identifying patients with renovascular hypertension. MR
      angiography should be favored in hypertensive patients who are resistant to
      medical therapy to avoid false-negative examinations.

PMID- 15728622
TI  - Cerebral vasoreactivity: a comparison of color velocity imaging quantification
      and stable xenon-enhanced CT.
AB  - OBJECTIVE: Compromised cerebral vasoreactivity increases the risk of stroke. In
      this study, we sought to determine whether extracranial arterial blood flow
      volume measured on color velocity imaging quantification could be predictive of
      cerebral vasoreactivity after the administration of acetazolamide. SUBJECTS AND
      METHODS: Cerebral blood flow and extracranial arterial blood flow volume of 35
      patients with symptomatic carotid occlusive disease were measured before and
      after the administration of acetazolamide on stable xenon CT and color velocity
      imaging quantification, respectively. The changes in unilateral extracranial
      arterial blood flow volume and respective hemispheric cerebral blood flow were
      compared. The mean difference in the percentage of change in flow volume, the 95%
      limit of agreement, and Cohen's kappa coefficient were calculated. RESULTS: A
      total of 64 unilateral extracranial arterial blood flow volume changes were
      successfully compared with the changes in the ipsilateral hemispheric cerebral
      blood flow. The mean difference in percentage of change in flow volume between
      the two techniques was 4.7%, with the 95% limit of agreement ranging from -90.2%
      to 99.7%. Cohen's kappa coefficient was 0.41 (95% confidence interval, 0.13-0.68;
      p = 0.001). CONCLUSION: The performance of color velocity imaging quantification
      for evaluating cerebral vasoreactivity is comparable to that of transcranial
      Doppler sonography. Because color velocity imaging quantification is not as
      limited as transcranial Doppler sonography, it could be an ideal complementary
      tool to transcranial Doppler sonography. More studies are required to define its
      clinical value.

PMID- 15728623
TI  - Midbrain ataxia: an introduction to the mesencephalic locomotor region and the
      pedunculopontine nucleus.
AB  - OBJECTIVE: Although gait ataxia is usually associated with cerebellar lesions, we
      review a less familiar cause. We present three patients with dorsal midbrain
      lesions and correlate these presentations with recent findings in the functional
      anatomy of the midbrain. CONCLUSION: We suggest that these lesions involve a well
      studied but generally unfamiliar area of the dorsal midbrain known as the
      mesencephalic locomotor region. More specifically, we hypothesize that
      involvement of the pedunculopontine nucleus, a major component of the
      mesencephalic locomotor region, may be at least partially responsible for
      producing midbrain ataxia.

PMID- 15728624
TI  - West Nile virus infection.
AB  - OBJECTIVE: Our objective is to present a brief review of the clinical aspects of
      West Nile virus infection with emphasis on the spectrum of MRI findings.
      CONCLUSION: West Nile virus infection has become endemic in the United States and
      radiologists should become aware of the diverse imaging appearances in the
      central nervous system.

PMID- 15728625
TI  - Superficial neurofibroma: a lesion with unique MRI characteristics in patients
      with neurofibromatosis type 1.
AB  - OBJECTIVE: Our aim was to test the hypothesis that in neurofibromatosis type 1
      (NF1), superficial plexiform neurofibromas have different MRI characteristics
      than deep plexiform neurofibromas. SUBJECTS AND METHODS: Sixty-six patients
      (median age, 15 years) with superficial plexiform neurofibromas were compared
      with 56 patients with deep plexiform neurofibromas (median age, 12 years). All
      patients underwent axial STIR and coronal or sagittal STIR images. RESULTS:
      Superficial neurofibromas were more likely to be asymmetric (p = 0.004) and
      extend to the skin surface (p < 0.001). Lesion borders were poorly defined with
      similar frequency in both superficial and deep groups (77% vs 68%, p = 0.31). The
      morphology of superficial neurofibromas was more likely diffuse (64% vs 11%, p <
      0.001), whereas deep neurofibromas were more likely nodular or fascicular. Of
      neurofibromas that were nodular or fascicular in morphology, superficial lesions
      had a smaller maximal fascicle-nodule diameter (mean, 10.3 mm) than deep lesions
      (mean, 13.4 mm) (p = 0.013). Signal characteristics of deep neurofibromas were
      more likely to be targetlike (75%) compared with superficial neurofibromas (21%)
      (p < 0.001). Superficial neurofibromas had a smaller mean volume than deep
      neurofibromas (180 vs 444 cm(3), p = 0.002). CONCLUSION: Unlike the typical
      targetlike lesions along the course of major nerves seen in deep plexiform
      lesions, superficial plexiform neurofibromas in NF1 tend to be asymmetric, have
      nontargetlike signal intensity, lack nodular or fascicular morphology, and are
      likely to involve skin.

PMID- 15728626
TI  - High-resolution sonography of the rib: can fracture and metastasis be
      differentiated?
AB  - OBJECTIVE: Our aim was to evaluate whether high-resolution sonography can provide
      additional information concerning rib lesions compared with radiography or bone
      scintigraphy. MATERIALS AND METHODS: Fifty-eight patients with high-uptake rib
      lesions seen on bone scintigraphy were selected. Radiography and rib high
      resolution sonography were performed on these patients. High-resolution
      sonography was performed using a linear 5-12 MHz transducer. By means of clinical
      history, histopathologic examination, and follow-up observation, these patients
      were classified into rib fracture (n = 37), rib metastasis (n = 18), or unknown
      (n = 3) groups. High-resolution sonography images of the 55 proven cases were
      reviewed for the presence of five representative findings: cortical disruption,
      callus formation, cortical deformity, mass, or bone destruction. The frequencies
      of these findings were compared between the groups with fracture and metastasis.
      RESULTS: Rib lesions were matched by bone scintigraphy and high-resolution
      sonography in 53 (96%) of 55 patients and by bone scintigraphy and plain
      radiography in 23 (42%) of 55 patients. High-resolution sonography revealed 17
      (94%) of 18 patients with metastasis and 36 (97%) of 37 patients with rib
      fractures. Metastatic lesions were seen as mass formation (n = 13) and irregular
      bone destruction (n = 7) on high-resolution sonography. Fracture was seen as
      cortical disruption with or without hematoma (n = 17), callus formation (n = 9),
      or cortical deformity, such as angling or stepping (n = 12). CONCLUSION: High
      resolution sonography of the ribs is a useful method of characterizing rib
      lesions in patients who have hot-uptake lesions on bone scintigraphy.

PMID- 15728627
TI  - Eosinophilic fasciitis: spectrum of MRI findings.
AB  - OBJECTIVE: Our objective was to describe the spectrum of MRI features of
      eosinophilic fasciitis. CONCLUSION: MRI findings in eosinophilic fasciitis are
      characteristic and consist of abnormal fascial signal intensity and enhancement,
      both of which are directly proportional to disease activity. MRI provides a
      useful aid for diagnosis and a marker for disease activity and response to
      treatment.

PMID- 15728628
TI  - MRI of medial malleolar bursa.
AB  - OBJECTIVE: This study was designed to assess the MR appearance of the medial
      perimalleolar fat in an asymptomatic population and describe the MRI appearance
      of the medial malleolar bursa. CONCLUSION: The MRI findings of medial
      perimalleolar fat in asymptomatic individuals and in patients with suspected
      medial malleolar bursa include normal fat, minimal or extensive subcutaneous
      edema, and a fluid-filled sac. The latter pattern is consistent with the MR
      appearance of the medial malleolar bursa.

PMID- 15728629
TI  - Glenoid dysplasia: incidence and association with posterior labral tears as
      evaluated on MRI.
AB  - OBJECTIVE: Glenoid dysplasia is known to predispose affected patients to
      accelerated degenerative joint disease. We have observed that there is often an
      association between glenoid dysplasia and posterior labral tears. Our goal was to
      assess glenoid dysplasia as seen on MRI and to assess its association with
      posterior labral tears. CONCLUSION: In our study population, we found that
      moderate to severe glenoid dysplasia is not a rare entity as seen on MRI, with an
      incidence of 14.3%. Furthermore, we found that there is a statistically
      significant increase in the incidence of posterior labral tears associated with
      shoulders with moderate or severe glenoid dysplasia compared with those shoulders
      with no dysplasia or mild dysplasia as evaluated on MRI. Even when the mild cases
      were included, the incidence of posterior labral tears was significantly
      increased versus healthy subjects, indicating that even mild cases of glenoid
      dysplasia may be clinically relevant.

PMID- 15728630
TI  - Quadrilateral space syndrome: incidence of imaging findings in a population
      referred for MRI of the shoulder.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of MRI
      findings suggesting quadrilateral space syndrome in a population referred for
      shoulder MRI. CONCLUSION: Focal teres minor atrophy or abnormal signal suggesting
      quadrilateral space syndrome is an uncommon, although not rare, finding on MRI of
      the shoulder in our referral population and is rarely an isolated abnormality.

PMID- 15728631
TI  - Supplemental value of MRI in fetal abdominal disease detected on prenatal
      sonography: preliminary experience.
AB  - OBJECTIVE: Our aim was to determine the supplemental value of MRI in fetal
      abdominal disease detected on prenatal sonography. CONCLUSION: Our preliminary
      results suggest the primary supplemental value of MRI relative to sonography in
      fetal abdominal disease lies in improved tissue characterization rather than in
      improved anatomic characterization.

PMID- 15728632
TI  - Borderline tumors of the ovary: CT and MRI features and tumor markers in
      differentiation from stage I disease.
AB  - OBJECTIVE: We sought to describe MDCT and MRI features and tumor marker levels
      that differentiate borderline ovarian tumors from stage I ovarian tumors.
      CONCLUSION: Borderline ovarian tumors are complex masses with imaging features
      similar to stage I tumors. The thickness of septations and the size of solid
      components are significantly larger in stage I tumors, and these features may be
      helpful for predicting likelihood of invasive tumors. However, neither feature
      allows confident differentiation of borderline tumors from stage I disease.

PMID- 15728633
TI  - Characterization of adnexal masses with MRI.

PMID- 15728634
TI  - Prenatal MRI of congenital abdominal and chest wall defects.

PMID- 15728635
TI  - Internet-based radiology order-entry, reporting, and workflow management system
      for coordinating urgent study requests during off-hours.
AB  - OBJECTIVE: Our aim was to develop a simple, low-cost, Internet-based application
      for radiology order-entry, reporting, and workflow management during off-hours.
      CONCLUSION: The system was quickly accepted by users both within and outside the
      radiology department, and it required very modest resources to develop, deploy,
      and support. In a busy on-call setting at a high-volume academic institution, the
      system described was effective in obtaining more thorough patient histories from
      referring physicians, reducing the number of telephone calls required, and
      documenting more rigorously the communication between radiologists and clinical
      services. These benefits allow the generation of more informative and timely
      radiology reports.

PMID- 15728636
TI  - The electronic viewbox.
AB  - OBJECTIVE: We describe an effective, resource-free method for facilitating the
      comparison of film-based and PACS-based radiographic studies. CONCLUSION: Side-by
      side comparison of film-based and PACS-based radiographic studies is often
      inconvenient because of the absence of an ergonomically satisfactory viewbox near
      the workstation. With a simple maneuver, any PACS display monitor can be used as
      a rudimentary viewbox, providing a convenient and ergonomically effective
      alternative.

PMID- 15728637
TI  - Pulmonary fibrosis of the upper lobes after lung transplantation is associated
      with selective CD8+ T lymphocyte expansion.

PMID- 15728638
TI  - Effects of chemical agents on hydatid cyst membranes.

PMID- 15728639
TI  - Use of dextrose 5% in water instead of saline to protect against inadvertent
      radiofrequency injuries.

PMID- 15728641
TI  - Solutions for extracting images from non-DICOM proprietary storage media.

PMID- 15728643
TI  - Pelvic fibromatosis with massive ossification.

PMID- 15728644
TI  - Aneurysm of aberrant right subclavian artery causing Dysphagia lusoria in an
      elderly patient.

PMID- 15728645
TI  - Intense metabolic control by means of insulin in patients with diabetes mellitus
      and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity.
AB  - AIMS: Patients with diabetes have an unfavourable prognosis after an acute
      myocardial infarction. In the first DIGAMI study, an insulin-based glucose
      management improved survival. In DIGAMI 2, three treatment strategies were
      compared: group 1, acute insulin-glucose infusion followed by insulin-based long
      term glucose control; group 2, insulin-glucose infusion followed by standard
      glucose control; and group 3, routine metabolic management according to local
      practice. METHODS AND RESULTS: DIGAMI 2 recruited 1253 patients (mean age 68
      years; 67% males) with type 2 diabetes and suspected acute myocardial infarction
      randomly assigned to groups 1 (n=474), 2 (n=473), and 3 (n=306). The primary
      endpoint was all-cause mortality between groups 1 and 2, and a difference was
      hypothesized as the primary objective. The secondary objective was to compare
      total mortality between groups 2 and 3, whereas morbidity differences served as
      tertiary objectives. The median study duration was 2.1 (interquartile range 1.03
      3.00) years. At randomization, HbA1c was 7.2, 7.3, and 7.3% in groups 1, 2, and
      3, respectively, whereas blood glucose was 12.8, 12.5, and 12.9 mmol/L,
      respectively. Blood glucose was significantly reduced after 24 h in all groups,
      more in groups 1 and 2 (9.1 and 9.1 mmol/L) receiving insulin-glucose infusion
      than in group 3 (10.0 mmol/L). Long-term glucose-lowering treatment differed
      between groups with multidose insulin (> or =3 doses/day) given to 15 and 13% of
      patients in groups 2 and 3, respectively compared with 42% in group 1 at hospital
      discharge. By the end of follow-up, HbA1c did not differ significantly among
      groups 1-3 ( approximately 6.8%). The corresponding values for fasting blood
      glucose were 8.0, 8.3, and 8.6 mmol/L. Hence, the target fasting blood glucose
      for patients in group 1 of 5-7 mmol/L was never reached. The study mortality
      (groups 1-3 combined) was 18.4%. Mortality between groups 1 (23.4%) and 2 (22.6%;
      primary endpoint) did not differ significantly (HR 1.03; 95% CI 0.79-1.34;
      P=0.831), nor did mortality between groups 2 (22.6%) and 3 (19.3%; secondary
      endpoint) (HR 1.23; CI 0.89-1.69; P=0.203). There were no significant differences
      in morbidity expressed as non-fatal reinfarctions and strokes among the three
      groups. CONCLUSION: DIGAMI 2 did not support the fact that an acutely introduced,
      long-term insulin treatment improves survival in type 2 diabetic patients
      following myocardial infarction when compared with a conventional management at
      similar levels of glucose control or that insulin-based treatment lowers the
      number of non-fatal myocardial reinfarctions and strokes. However, an
      epidemiological analysis confirms that the glucose level is a strong, independent
      predictor of long-term mortality in this patient category, underlining that
      glucose control seems to be an important part of their management.

PMID- 15728646
TI  - Skeletal myoblast transplantation through a catheter-based coronary sinus
      approach: an effective means of improving function of infarcted myocardium.
AB  - AIMS: This study was designed to assess the functional effects of a transvenous
      coronary sinus technique of skeletal myoblast delivery in infarcted myocardium.
      METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously
      in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two
      weeks later, sheep were instrumented percutaneously with a dedicated catheter
      incorporating an extendable needle for puncture of the venous wall and, under
      endovascular ultrasound guidance, a microcatheter was advanced through the needle
      into the target scar for cell delivery. Following the baseline echocardiographic
      assessment of left ventricular (LV) function, sheep were randomly allocated to
      receive four-staged in-scar injections of either autologous cells (n=7) or
      culture medium (n=7). Two months later, LV function was reassessed blindly and
      hearts were explanted for subsequent histological and immunohistochemical
      analysis. There were no acute procedural complications. Baseline LV ejection
      fraction (EF) was significantly lower in transplanted sheep than in controls [38%
      (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later,
      LVEF was significantly higher in the transplanted group than in controls [50% (47
      56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were
      identified by histology and immunohistochemistry in three of the seven
      transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the
      transvenous coronary sinus technique as a less invasive means of cell delivery to
      infarcted myocardium.

PMID- 15728647
TI  - Do statins influence the prognostic impact of non-sustained ventricular
      tachycardia after ST-elevation myocardial infarction?
AB  - AIMS: The study evaluates the effect of statin therapy on the prognostic impact
      of non-sustained ventricular tachycardia (NSVT) occurring after acute ST
      elevation myocardial infarction (STEMI). METHODS AND RESULTS: From the German
      Acute Coronary Syndrome Registry (ACOS), 3137 patients with STEMI and in-hospital
      Holter monitoring were analysed. Three hundred and forty-six (11.0%) patients had
      NSVT. When compared with patients with no documented NSVT, patients with NSVT
      were older, more often had myocardial infarction in their history, diabetes
      mellitus, and an ejection fraction <40%. Regarding frequency of drug application,
      medication at discharge did not (beta-blockers, ACE-inhibitors, amiodarone) or
      only slightly (acetylsalicylic acid, statins, and sotalol) differ between both
      groups. Multivariable analysis of 1 year mortality, adjusted for age, gender,
      diabetes, reperfusion therapy, ejection fraction <40%, and beta-blocker therapy
      showed the following results: In patients without statin treatment and no NSVT, 1
      year mortality after STEMI was 9.2%, but increased to 25.0% [odds ratio (OR)
      3.02; 95% confidence interval (CI) 1.47-6.20], if NSVT were present. In patients
      on statin treatment and no NSVT, 1 year mortality was only 3.2%, and in the
      presence of NSVT 1 year mortality was not significantly increased anymore (5.3%;
      OR 1.03; 95% CI 0.55-1.92). CONCLUSION: After STEMI, only in patients not on
      statin treatment, the occurrence of NSVT is associated with a significant and
      marked increase in 1 year mortality.

PMID- 15728648
TI  - Clinical and electrocardiographic predictors of a positive response to cardiac
      resynchronization therapy in advanced heart failure.
AB  - AIMS: Cardiac resynchronization therapy (CRT) is an effective treatment for
      refractory congestive heart failure (CHF). However, up to 30% of patients do not
      respond to CRT. The aim of this study was to identify clinical and
      electrocardiographic (ECG) predictors of a positive response to CRT. METHODS AND
      RESULTS: This retrospective study included 139 consecutive patients successfully
      implanted with a CRT device (mean age, 68+/-9 years, 113 men). At baseline, 69%
      of patients were in New York Heart Association (NYHA) functional class III, and
      31% in class IV, mean left ventricular ejection fraction was 21+/-6%, and mean
      QRS duration was 188+/-28 ms. In each patient, left and right ventricular leads
      were placed to attain the shortest QRS duration during biventricular stimulation.
      Patients were classified at 6 months as responders to CRT (n=100) if they were
      alive, they had not been re-hospitalized for management of CHF, and the NYHA
      class had decreased by 1 point, and/or peak VO(2) or 6 min hall-walk increased by
      >10%. All others were classified as non-responders (n=38; one patient was lost to
      follow-up). Uni- and multivariate logistic regression analyses were performed to
      detect a pre- or intra-operative predictor of a positive response to CRT. Among
      multiple demographic, clinical, and ECG variables, the amount of QRS shortening
      (DeltaQRS) associated with biventricular stimulation was the only independent
      predictor of a positive (37+/-23 ms) vs. negative (11+/-23 ms) response to CRT
      (P<0.001). CONCLUSION: A positive response to CRT was observed in 73% of patients
      at 6 months and predicted only by DeltaQRS.

PMID- 15728649
TI  - The variation of morphological and functional cardiac manifestation in Fabry
      disease: potential implications for the time course of the disease.
AB  - AIMS: The aim of this clinical cross-sectional study was to investigate the
      cardiac interrelation of morphological and functional abnormalities in patients
      with Fabry disease. METHODS AND RESULTS: Fifty-one patients (5-78 years) were
      compared with 25 controls (8-77 years). In all subjects, end-diastolic thickness
      of the left ventricle was measured by echocardiography and ultrasonic peak
      systolic strain rate (SR) was extracted to assess regional myocardial function.
      Magnetic resonance imaging was performed to assess late-enhancement for the
      detection of myocardial fibrosis in Fabry patients (n=39). In patients, women <20
      years of age had no hypertrophy, no late-enhancement, and normal radial and
      longitudinal function (SR longitudinal=-1.7+/-0.5 s(-1); P=n.s. compared with
      controls). Ten women, >20 years of age, had no hypertrophy, no late-enhancement,
      normal radial and longitudinal function in the septal wall, but reduced
      longitudinal function in the lateral wall (SR=-1.4+/-0.5 s(-1)). All male
      patients without hypertrophy and no late-enhancement had normal radial function
      but reduced longitudinal function in both the septal and lateral walls (SR=-1.3+/
      0.3 s(-1)). Patients with hypertrophy but without late-enhancement (n=13) had
      reduced radial and longitudinal function. Twelve patients displaying hypertrophy
      and late-enhancement had severely reduced radial and longitudinal function (SR=
      1.1+/-0.5 s(-1)). Two of them with the worst impairment of regional function (SR=
      0.8+/-0.6 s(-1)) died in the follow-up period. CONCLUSION: These results
      illustrate the variation of morphological changes and its functional consequences
      in Fabry cardiomyopathy.

PMID- 15728650
TI  - Stent thrombosis following bare-metal stent implantation: success of emergency
      percutaneous coronary intervention and predictors of adverse outcome.
AB  - AIMS: To investigate the efficacy and outcome of emergency percutaneous coronary
      interventions (PCI) in patients with stent thrombosis. METHODS AND RESULTS:
      Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of
      which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent
      thrombosis was acute in 10 (11%), subacute in 61 (64%), and late in 24 (25%)
      patients. Procedural and clinical outcomes of emergency PCI for treatment of
      stent thrombosis were investigated. Emergency PCI was successful in 86 (91%),
      complicated by death in 2 (2%), and coronary artery bypass grafting in 2 (2%)
      patients. Myocardial infarction occurred in 77 (81%) patients with a peak
      creatine kinase level of 1466+/-1570 U/L. Left ventricular ejection fraction
      declined from 0.54+/-0.19 prior to 0.48+/-0.16 (P<0.05) at the time of stent
      thrombosis after emergency PCI. A 6 month major adverse clinical events comprised
      death (11%), reinfarction (16%), and recurrent stent thrombosis (12%) after
      emergency PCI. Multivariable logistic regression analysis identified the
      achievement of TIMI 3 flow (OR=0.1, CI 95% 0.01-0.54, P<0.001) and diameter
      stenosis <50% (OR=0.06, CI 95% 0.01-0.32, P<0.001) during emergency PCI to be
      independently associated with a reduced risk of cardiac death. Recurrent stent
      thrombosis was independently predicted by the omission of abciximab (OR=4.3, CI
      95% 1.1-17.5). CONCLUSION: Emergency PCI for treatment of stent thrombosis
      effectively restores vessel patency and flow. Patients presenting with stent
      thrombosis are at risk for recurrent myocardial infarction and recurrent stent
      thrombosis.

PMID- 15728651
TI  - Sign and speech: amodal commonality in left hemisphere dominance for
      comprehension of sentences.
AB  - The neural basis of functional lateralization in language processing is a
      fundamental issue in systems neuroscience. We used functional MRI (fMRI) to
      examine hemispheric dominance during the processing of signed and spoken
      sentences. By using tasks involving comprehension of sentences (Sc) and
      sentential non-word detection (Sn), we compared different groups and stimulus
      conditions. Under the sign condition with sentence stimuli in Japanese Sign
      Language (JSL), we tested two groups of subjects: Deaf signers (Deaf) of JSL, and
      hearing bilinguals (children of Deaf adults, CODA) of JSL and Japanese (JPN).
      Under the speech condition, we tested hearing monolinguals (Mono) of JPN with
      auditory JPN stimuli alone (AUD), or with an audiovisual presentation of JPN and
      JSL stimuli (A&V). We found that the overall bilateral activation patterns under
      the four experimental conditions of Deaf, CODA, AUD and A&V were almost
      identical, despite differences in stimuli (JSL and JPN) and groups (Deaf, CODA
      and Mono). Moreover, consistently left-dominant activations involving frontal and
      temporo-parietal regions were observed across all four conditions. Furthermore,
      irrespective of the modalities of sign and speech, the main effects of task (Sc
      Sn) were found primarily in the left regions: the ventral part of the inferior
      frontal gyrus (F3t/F3O), the precentral sulcus, the superior frontal gyrus, the
      middle temporal gyrus, the angular gyrus and the inferior parietal gyrus. Among
      these regions, only the left F3t/F3O showed no main effects of modality
      condition. These results demonstrate amodal commonality in the functional
      dominance of the left cortical regions for comprehension of sentences, as well as
      the essential and universal role of the left F3t/F3O in processing linguistic
      information from both signed and spoken sentences.

PMID- 15728652
TI  - Vicarious function within the human primary motor cortex? A longitudinal fMRI
      stroke study.
AB  - While experimental studies in the monkey have shown that motor recovery after
      partial destruction of the hand motor cortex was based on adjacent motor
      reorganization, functional MRI (fMRI) studies with isolated primary motor
      cortical stroke have not yet been reported in humans. Based on experimental data,
      we designed a study to test if recovery after stroke within primary motor cortex
      (M1) was associated with reorganization within the surrounding motor cortex, i.e.
      the motor cortex was able to vicariate. Since motor recovery is time-dependent
      and might be inflected according to the tested task, the delay after stroke and
      two motor tasks were included in our design. We examined four patients with one
      ischaemic stroke limited to M1, and four sex- and age-matched healthy controls in
      a temporally balanced prospective longitudinal fMRI study over three sessions:
      <20 days, 4 months and 2 years after stroke. The paradigm included two motor
      tasks, finger tapping (FT) and finger extension (FE). Distinct patterns of motor
      activation were observed with time for FT and FE. At the first session, FT
      related activation was lateralized in the ipsilateral hemisphere while FE-related
      activation was contralateral, involving bilateral cerebellar regions for both
      tasks. From 4 months, skilled motor recovery was associated with contralateral
      dorsal premotor and sensorimotor cortex and ipsilateral cerebellum motor-related
      activations, leading to lateralized motor patterns for both tasks. For the left
      recovered hand, FT and FE-related activations within M1 were more dorsal in
      patients than in controls. This dorsal shift progressively increased over 2
      years, reflecting functional reorganization in the motor cortex adjacent to the
      lesion. In addition, patients showed a reverse representation of FT and FE within
      M1, corresponding to a greater dorsal shift for FT than for FE. This functional
      dissociation might reflect the structural subdivision of M1 with two distinct
      finger motor representations within M1. Recovery of FT, located within the
      lesioned depth of the rolandic sulcus in controls, might be related to the re
      emergence of a new representation in the intact dorsal M1, while FE, located more
      dorsally, underwent minor reorganization. This is the first fMRI study of humans
      presenting with isolated M1 stroke comparable with experimental lesions in
      animals. Despite the small number of patients, our findings showing the re
      emergence of a fingers motor task in the intact dorsal M1 instead of in ventral
      M1 are consistent with 'vicariation' models of stroke recovery.

PMID- 15728653
TI  - Isolation of transcriptomal changes attributable to LHON mutations and the
      cybridization process.
AB  - Leber's hereditary optic neuropathy (LHON) is thought to be the most common
      disease resulting from mitochondrial DNA (mtDNA) point mutations, and
      transmitochondrial cytoplasmic hybrid (cybrid) cell lines are the most frequently
      used model for understanding the pathogenesis of mitochondrial disorders. We have
      used oligonucleotide microarrays and a novel study design based on shared
      transcripts to allocate transcriptomal changes into rho-zero-dependent,
      cybridization-dependent and LHON-dependent categories in these cells. The
      analysis indicates that the rho-zero process has the largest transcriptomal
      impact, followed by the cybridization process, and finally the LHON mutations.
      The transcriptomal impacts of the rho-zero and cybridization processes
      preferentially and significantly affect the mitochondrial compartment, causing
      upregulation of many transcripts involved in oxidative phosphorylation,
      presumably in response to the mtDNA depletion that occurs at the rho-zero step.
      Nine LHON-specific transcriptional alterations were shared among osteosarcoma
      cybrids and lymphoblasts bearing LHON mutations. Notably, the aldose reductase
      transcript was overexpressed in LHON cybrids and lymphoblasts. Aldose reductase
      is also overexpressed in diabetic retinopathy, leading to optic nerve and retinal
      complications. The LHON-specific increase in transcript level was confirmed by
      quantitative reverse transcription-polymerase chain reaction (RT-PCR), and a
      western blot confirmed a higher level of aldose reductase in mutant mitochondria.
      One product of aldose reductase is sorbitol, which has been linked to osmotic
      stress, oxidative stress and optic neuropathy, and sorbitol levels were increased
      in LHON cybrids. If these results are confirmed in patient tissues, aldose
      reductase inhibitors could have some therapeutic value for LHON.

PMID- 15728654
TI  - Cortical triggers in generalized reflex seizures and epilepsies.
AB  - Activation of specific cortical territories by sensory stimuli or of less
      restricted areas of the brain by cognitive stimuli is known to induce apparently
      generalized seizures in predisposed patients; this is clinically and
      electroencephalographically distinct from reflex triggering of partial seizures.
      Photosensitive patients may have seizures when exposed to environmental stimuli
      producing appropriate flickering light or geometric patterns. Some children with
      benign myoclonic epilepsy in infancy have seizures triggered by unexpected touch
      or noise. Seizures induced by thinking have been reported in response to non
      verbal higher mental activity such as mental arithmetic. Praxis-induced seizures
      are triggered by similar mental activities accompanied by the use of the hands.
      Language-induced seizures are usually triggered by verbal higher mental activity.
      Functional imaging and other methods have contributed to understanding how these
      seizures arise. Patients with these generalized reflex seizures appear to have
      regions of cortical hyperexcitability overlapping or coinciding with areas
      physiologically activated during specific sensory stimulations and cognitive or
      motor activities. When these areas receive appropriate afferent volleys and a
      critical mass of cortex is activated, an epileptic activity is produced that
      ultimately involves cortico-reticular or cortico-cortical pathways resulting in a
      generalized or bilateral epileptic event.

PMID- 15728655
TI  - Correlations between granule cell physiology and bioenergetics in human temporal
      lobe epilepsy.
AB  - Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormalities
      including decreased phosphocreatine (PCr) normalized to ATP. The physiological
      consequences of these metabolic alterations have not been established. We
      hypothesized that impaired bioenergetics would correlate with alterations in
      physiological functions under conditions that strongly activate neural
      metabolism. We correlated several physiological variables obtained from epileptic
      human dentate granule cells studied in slices with hippocampal PCr/ATP measured
      using in vivo magnetic resonance spectroscopy. The physiological variables
      included: the ability to fire multiple action potentials in response to single
      stimuli, the inhibitory postsynaptic potential (IPSP) conductance and the
      responses to a 10 Hz, 10 s stimulus train. We noted a significant negative
      correlation between the ability to fire multiple spikes in response to single
      synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between
      the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong
      correlation between PCr/ATP and the recovery of the membrane potential following
      a stimulus train (P < 0.01), with low PCr/ATP being associated with prolonged
      recovery times. These data suggest that the bioenergetic impairment seen in this
      tissue is associated with specific changes in excitatory and inhibitory neuronal
      responses to synchronized synaptic inputs.

PMID- 15728656
TI  - Subdural recordings of the mismatch negativity (MMN) in patients with focal
      epilepsy.
AB  - Mismatch negativity (MMN) is elicited by discernible changes in an otherwise
      regular stream of auditory stimulation and reflects a pre-attentive detection
      mechanism. In the current study, auditory evoked potentials were recorded
      intracranially and electrode contacts sensitive for stimulus deviance were
      selected in order to further elucidate the contribution of different brain areas
      to MMN generation. Data were obtained from patients with frontal and temporal
      lobe epilepsy undergoing a presurgical evaluation by subdural and depth
      electrodes. In 13 of 29 patients under investigation an intracranial MMN could be
      observed, while in four other patients a response recovery of the N100 was
      revealed, mimicking an MMN. Most electrodes with an MMN signal were located in or
      close to the superior temporal lobe. In two patients an MMN was observed at
      electrode contacts over the lateral inferior frontal cortex and in one patient at
      a frontal interhemispheric electrode strip, giving evidence for a participation
      of the frontal gyrus in MMN generation. Current findings have, however, to be
      interpreted with caution owing to the placement and limited extension of the used
      electrode arrays.

PMID- 15728657
TI  - The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study.
AB  - Opioids have been shown to provide symptomatic relief from dysaesthesias and
      motor symptoms in restless legs syndrome (RLS). However, the mechanisms by which
      endogenous opioids contribute to the pathophysiology of RLS remain unknown. We
      have studied opioid receptor availability in 15 patients with primary RLS and 12
      age-matched healthy volunteers using PET and [11C]diprenorphine, a non-selective
      opioid receptor radioligand. Ligand binding was quantified by generating
      parametric images of volume of distribution (V(d)) using a plasma-derived input
      function. Statistical parametric mapping (SPM) was used to localize mean group
      differences between patients and controls and to correlate ligand binding with
      clinical scores of disease severity. There were no mean group differences in
      opioid receptor binding between patients and controls. However, we found regional
      negative correlations between ligand binding and RLS severity (international
      restless legs scale, IRLS) in areas serving the medial pain system (medial
      thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex and
      orbitofrontal cortex). Pain scores (affective component of the McGill Pain
      Questionnaire) correlated inversely with opioid receptor binding in orbitofrontal
      cortex and anterior cingulate gyrus. Our findings suggest that, the more severe
      the RLS, the greater the release of endogenous opioids within the medial pain
      system. We therefore discuss a possible role for opioids in the pathophysiology
      of RLS with respect to sensory and motor symptoms.

PMID- 15728658
TI  - Motor cortex excitability in focal epilepsies not including the primary motor
      area--a TMS study.
AB  - It is unclear whether focal epilepsies chronically influence the processing of
      cortex distant to the epileptogenic zone. Therefore, motor cortex excitability
      was analysed in patients with temporal and extratemporal epilepsies whose
      epileptogenic zones did not include the primary motor area. Single and paired
      pulse transcranial magnetic stimulation (TMS) was applied to the primary motor
      cortex in 20 healthy controls and 23 patients with focal epilepsy (39.4 +/- 13.2
      years; 12 left, 11 right; 14 temporal, nine extratemporal: six frontal, three
      parieto-occipital) ipsi- and contralateral to the epileptogenic zone. In all
      patients, the epileptogenic zone did not include the primary motor cortex. The
      resting motor threshold (RMT), the cortical silent period (CSP), the
      intracortical inhibition [ICI; combined interstimulus intervals (ISI) 2 and 3 ms]
      and the intracortical facilitation (ICF; combined ISI 10 and 15 ms) were
      determined. The measures obtained ipsilateral to the epileptogenic zone were
      compared with those elicited in contralateral hemispheres and, in exploratory
      analyses, with controls using non-parametric tests, including Hodges-Lehmann
      estimates of median differences (HLE) with 95% confidence intervals (CI). In the
      patient group, the CSP elicited in the ipsilateral motor cortex (median 162.3 ms)
      was shortened compared with the contralateral CSP (median 174.6 ms; HLE 15.9 ms;
      CI 6.2, 27.0 ms; P = 0.002). This interhemispheric difference was more pronounced
      in extratemporal epilepsies (HLE 23.4 ms; CI -3.2, 67.6 ms) compared with
      temporal epilepsies (HLE 14.3 ms; CI 4.7, 26.2 ms). Patients with parieto
      occipital epilepsies showed the greatest interhemispheric differences in CSP (HLE
      33.5 ms) and patients with mesial temporal epilepsies the smallest (HLE 9.9 ms).
      No significant differences were found between ipsi- and contralateral RMT, ICI or
      ICF. In analyses of subgroups, the CSP was shorter in epileptic hemispheres of
      patients with extratemporal epilepsies (141.4 ms) than in controls (173.4 ms; HLE
      40.0 ms; CI 3.2, 83.4 ms; P = 0.029). ICF was increased in epileptic hemispheres
      of extratemporal epilepsies (147.6%) compared with temporal epilepsies (114.6%;
      HLE 33.0%; CI 4.1, 68.3%; P = 0.038). The results suggest that focal epilepsies
      influence chronically distant cortex, leading to decreased inhibition and
      increased facilitation in the ipsilateral motor cortex even when the
      epileptogenic zone is apart from it. This alteration may be due to synaptic
      reorganization and appears to be more pronounced in extratemporal and neocortical
      temporal than in mesial temporal epilepsies. This may have diagnostic
      implications.

PMID- 15728660
TI  - Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle
      cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels.
AB  - Increased matrix metalloproteinase-9 (MMP-9) expression is associated with
      intimal hyperplasia in saphenous vein (SV) bypass grafts. Recent evidence
      suggests that HMG-CoA reductase inhibitors (statins) can prevent the progression
      of vein graft failure. Here we investigated whether statins inhibited MMP-9
      secretion from cultured human SV smooth muscle cells (SMC) and examined the
      underlying mechanisms. SV-SMC from different patients were exposed to phorbol
      ester (TPA) or PDGF-BB plus interleukin-1alpha (IL-1). MMP-9 secretion and mRNA
      expression were analyzed using gelatin zymography and RT-PCR, respectively.
      Specific signal transduction pathways were investigated by immunoblotting and
      pharmacological inhibition. Simvastatin reduced TPA- and PDGF/IL-1-induced MMP-9
      secretion and mRNA levels, effects reversed by geranylgeranyl pyrophosphate and
      mimicked by inhibiting Rho geranylgeranylation or Rho-kinase (ROCK). MMP-9
      secretion induced by PDGF/IL-1 was mediated via the ERK, p38 MAPK, and NFkappaB
      pathways, whereas that induced by TPA was mediated specifically via the ERK
      pathway. Simvastatin failed to inhibit activation of these signaling pathways.
      Moreover, simvastatin did not affect MMP-9 mRNA stability. Together these data
      suggest that simvastatin reduces MMP-9 secretion from human SV-SMC by inhibiting
      the RhoA/ROCK pathway and decreasing MMP-9 mRNA levels independently of effects
      on signaling pathways required for MMP-9 gene expression.

PMID- 15728661
TI  - Mitochondrial function is a critical determinant of IL-1-induced ERK activation.
AB  - Interleukin-1 (IL-1) is a potent, proinflammatory cytokine, but local
      environmental factors in inflamed sites or in sepsis may affect cell metabolism
      and energetics, including the amplitude and duration of IL-1-induced signals,
      thereby leading to loss of tissue homeostasis. Currently, the mechanisms by which
      disruption of cell energetics affects inflammatory signaling are incompletely
      understood. Here, we examined the impact of cell energetics and mitochondrial
      function on the regulation of IL-1-induced Ca2+ signals and ERK activation in
      human gingival fibroblasts, cells that are important targets for IL-1-induced
      destruction of extracellular matrix in inflamed connective tissues. In untreated
      cells, IL-1 induced a prolonged increase of free intracellular calcium, which was
      required for ERK activation. Inhibition of cellular energetics by selective
      depolarization of mitochondria blocked Ca2+ uptake and almost completely
      abolished IL-1-induced cytosolic Ca2+ signals and ERK activation. IL-1 caused
      rapid Ca2+ release from the endoplasmic reticulum (ER), concomitant with
      mitochondrial Ca2+ uptake from ER and non-ER stores. Disruption of mitochondrial
      energetics abrogated IL-1 induced Ca2+ release from the ER but left other vital
      cellular functions intact. The negative effect of mitochondrial depolarization on
      ER release was bypassed by BAPTA/AM, indicating that mitochondrial Ca2+ buffering
      is the key mechanism in regulating ER release. Thus, in gingival fibroblasts,
      mitochondrial Ca2+ uptake is essential not only for shaping the kinetics and
      duration, but also the generation of, IL-1-induced Ca2+ signals. Consequently,
      mitochondria regulate key downstream effectors of IL-1, including MAP kinases.

PMID- 15728662
TI  - Skeletal muscle gene expression profiling in mitochondrial disorders.
AB  - Extremely variable clinic and genetic features characterize mitochondrial
      encephalomyopathy (MEM). Pathogenic mitochondrial DNA (mtDNA) defects can be
      divided into large-scale rearrangements and single point mutations. Clinical
      manifestations become evident when a threshold percentage of the total mtDNA is
      mutated. In some MEM, the "mutant load" in an affected tissue is directly related
      to the severity of the phenotype. However, the clinical phenotype is not simply a
      direct consequence of the relative abundance of mutated mtDNA. Other factors,
      such as nuclear background, can contribute to the disease process, resulting in a
      wide range of phenotypes caused by the same mutation. Using Affymetrix
      oligonucleotide cDNA microarrays (HG-U133A), we studied the gene expression
      profile of muscle tissue biopsies obtained from 12 MEM patients [4 common 4977 bp
      deleted mtDNA and 8 A3243G: 4 progressive external ophthalmoplegia (PEO) and 4
      mitochondrial myopathy, encephalopathy, lactic cidosis, and stroke-like episodes
      syndrome (MELAS) phenotypes] compared with age-matched healthy individuals. We
      found several differentially expressed genes: 35 were markedly up-regulated in
      the mtDNA macro-deletion group (vs. the control group) and 4 decreased; 56 genes
      were dysregulated in A3243G-related disorders (53 down-regulated in PEO and 3 up
      regulated in MELAS). Finally, 12 genes were similarly regulated in the majority
      of the MEM patients under study. Amongst these, we identified an increased
      expression of genes related to the metabolism of the amino groups, as well as of
      several genes involved in genetic information processing. Moreover, few genes
      were similarly decreased in MEM patients vs. the control group. Real-time PCR
      demonstrated excellent reproducibility of the microarray-based findings. The
      observed expression changes are likely to represent a molecular signature for
      mitochondrial disorders. Furthermore, the differential expression profile of
      MELAS(A3243G) vs. PEO(A3243G) may support a role of nuclear background in
      contributing to these different clinical phenotypes. MEM microarray data are
      available from GEO database (http://www.ncbi.nlm.nih.gov/geo/) with the accession
      number: GSE1462.

PMID- 15728663
TI  - Adult neural stem cell cycling in vivo requires thyroid hormone and its alpha
      receptor.
AB  - Thyroid hormones (TH) are essential for brain development. However, information
      on if and how this key endocrine factor affects adult neurogenesis is
      fragmentary. We thus investigated the effects of TH on proliferation and
      apoptosis of stem cells in the subventricular zone (SVZ), as well as on migration
      of transgene-tagged neuroblasts out of the stem cell niche. Hypothyroidism
      significantly reduced all three of these processes, inhibiting generation of new
      cells. To determine the mechanisms relaying TH action in the SVZ, we analyzed
      which receptor was implicated and whether the effects were played out directly at
      the level of the stem cell population. The alpha TH receptor (TRalpha), but not
      TRbeta, was found to be expressed in nestin positive progenitor cells of the SVZ.
      Further, use of TRalpha mutant mice showed TRalpha to be required to maintain
      full proliferative activity. Finally, a direct TH transcriptional effect, not
      mediated through other cell populations, was revealed by targeted gene transfer
      to stem cells in vivo. Indeed, TH directly modulated transcription from the c-myc
      promoter reporter construct containing a functional TH response element
      containing TRE but not from a mutated TRE sequence. We conclude that liganded
      TRalpha is critical for neurogenesis in the adult mammalian brain.

PMID- 15728664
TI  - A central role for ceramide in the age-related acceleration of apoptosis in the
      female germline.
AB  - An age-dependent acceleration of apoptosis occurs in female germ cells (oocytes),
      and this requires communication between the oocyte and its surrounding somatic
      (cumulus) cells. Here we show in aged mice that ceramide is translocated from
      cumulus cells into the adjacent oocyte and induces germ cell apoptosis that can
      be prevented by sphingosine-1-phosphate. Trafficking of ceramide requires gap
      junction-dependent communication between the cumulus cells and the oocyte as well
      as intact lipid rafts. Further, the occurrence of the elevated incidence of
      apoptosis in oocytes of aged females is concomitant with an enhanced sensitivity
      of the oocyte to a spike in cytosolic ceramide levels, as well as increased bax
      mRNA and Bax protein levels. Thus, the force driving the age-related increase in
      female germ cell death is multifactorial, but changes in the intercellular
      trafficking of ceramide, along with hypersensitivity of oocytes to ceramide, are
      key factors in this process.

PMID- 15728665
TI  - Pseudocopulatory pollination in lepanthes (orchidaceae: pleurothallidinae) by
      fungus gnats.
AB  - BACKGROUND AND AIMS: Lepanthes is one of the largest angiosperm genera (>800
      species). Their non-rewarding, tiny and colourful flowers are structurally
      complex. Their pollination mechanism has hitherto remained unknown, but has been
      subject of ample speculation; the function of the minuscule labellum appendix is
      especially puzzling. Here, the pollination of L. glicensteinii by sexually
      deceived male fungus gnats is described and illustrated. METHODS: Visitors to
      flowers of L. glicensteinii were photographed and their behaviour documented;
      some were captured for identification. Occasional visits to flowers of L.
      helleri, L. stenorhyncha and L. turialvae were also observed. Structural features
      of flowers and pollinators were studied with SEM. KEY RESULTS: Sexually aroused
      males of the fungus gnat Bradysia floribunda (Diptera: Sciaridae) were the only
      visitors and pollinators of L. glicensteinii. The initial long-distance
      attractant seems to be olfactory. Upon finding a flower, the fly curls his
      abdomen under the labellum and grabs the appendix with his genitalic claspers,
      then dismounts the flower and turns around to face away from it. The pollinarium
      attaches to his abdomen during this pivoting manoeuvre. Pollinia are deposited on
      the stigma during a subsequent flower visit. The flies appear to ejaculate during
      pseudocopulation. The visitors of L. helleri, L. stenorhyncha and L. turialvae
      are different species of fungus gnats that display a similar behaviour.
      CONCLUSIONS: Lepanthes glicensteinii has genitalic pseudocopulatory pollination,
      the first case reported outside of the Australian orchid genus Cryptostylis.
      Since most species of Lepanthes have the same unusual flower structure, it is
      predicted that pollination by sexual deception is prevalent in the genus. Several
      morphological and phenological traits in Lepanthes seem well suited for
      exploiting male fungus gnats as pollinators. Correspondingly, some demographic
      trends common in Lepanthes are consistent with patterns of male sciarid
      behaviour.

PMID- 15728666
TI  - Adaptations to foliar absorption of faeces: a pathway in plant carnivory.
AB  - BACKGROUND AND AIMS: Roridula plants capture insects but have no digestive
      enzymes. It has been hypothesized that Roridula leaves absorb nitrogen from the
      faeces of obligately associated, carnivorous hemipterans. But rapid movement
      across the leaf surfaces of most plant leaves is prevented by the presence of an
      impermeable cuticle. However, in carnivorous plants, cuticular gaps or pores in
      digestive/absorptive cells allow rapid movement across the leaf surface.
      Recently, it was suggested that the hemipteran-plant interaction constituted a
      new pathway for plant carnivory. Here, a further adaptation to this pathway is
      described by demonstrating how Roridula plants probably absorb hemipteran faeces
      rapidly through their leaf cuticles. METHODS: The dye neutral red was used to
      document the rapidity of foliar absorption and TEM to determine the nature of
      cuticular discontinuities in the leaf of Roridula. KEY RESULTS: Aqueous compounds
      diffuse rapidly across the cuticle of Roridula's leaves but not across the
      cuticles of co-occurring, non-carnivorous plant leaves. Furthermore, immature
      Roridula leaves were unable to absorb neutral red whereas mature leaves could.
      Using TEM, cuticular gaps and pores similar to those in other carnivorous plants
      were found in the epidermal cells of mature Roridula leaves. CONCLUSIONS: The
      leaf cuticle of Roridula is very thin (0-120 nm) and cell wall elements project
      close to the leaf surface, possibly enhancing foliar absorption. In addition to
      these, cuticular gaps were frequently seen and probably perform a function
      similar to those found in other carnivorous plants: namely the absorption of
      aqueous compounds. The cuticular gaps of Roridula are probably an adaptation to
      plant carnivory, supporting the newly described pathway.

PMID- 15728667
TI  - Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes.
AB  - The diverse cellular contributions to the skeletal elements of the vertebrate
      shoulder and pelvic girdles during embryonic development complicate the study of
      their patterning. Research in avian embryos has recently clarified part of the
      embryological basis of shoulder formation. Although dermomyotomal cells provide
      the progenitors of the scapular blade, local signals appear to have an essential
      guiding role in this process. These signals differ from those that are known to
      pattern the more distal appendicular skeleton. We have studied the impact of
      Tbx15, Gli3, Alx4 and related genes on formation of the skeletal elements of the
      mouse shoulder and pelvic girdles. We observed severe reduction of the scapula in
      double and triple mutants of these genes. Analyses of a range of complex
      genotypes revealed aspects of their genetic relationship, as well as functions
      that had been previously masked due to functional redundancy. Tbx15 and Gli3
      appear to have synergistic functions in formation of the scapular blade. Scapular
      truncation in triple mutants of Tbx15, Alx4 and Cart1 indicates essential
      functions for Alx4 and Cart1 in the anterior part of the scapula, as opposed to
      Gli3 function being linked to the posterior part. Especially in Alx4/Cart1
      mutants, the expression of markers such as Pax1, Pax3 and Scleraxis is altered
      prior to stages when anatomical aberrations are visible in the shoulder region.
      This suggests a disorganization of the proximal limb bud and adjacent flank
      mesoderm, and is likely to reflect the disruption of a mechanism providing
      positional cues to guide progenitor cells to their destination in the pectoral
      girdle.

PMID- 15728668
TI  - ROXY1, a member of the plant glutaredoxin family, is required for petal
      development in Arabidopsis thaliana.
AB  - We isolated three alleles of an Arabidopsis thaliana gene named ROXY1, which
      initiates a reduced number of petal primordia and exhibits abnormalities during
      further petal development. The defects are restricted to the second whorl of the
      flower and independent of organ identity. ROXY1 belongs to a subgroup of
      glutaredoxins that are specific for higher plants and we present data on the
      first characterization of a mutant from this large Arabidopsis gene family for
      which information is scarce. ROXY1 is predominantly expressed in tissues that
      give rise to new flower primordia, including petal precursor cells and petal
      primordia. Occasionally, filamentous organs with stigmatic structures are formed
      in the second whorl of the roxy1 mutant, indicative for an ectopic function of
      the class C gene AGAMOUS (AG). The function of ROXY1 in the negative regulation
      of AG is corroborated by premature and ectopic AG expression in roxy1-3 ap1-10
      double mutants, as well as by enhanced first whorl carpeloidy in double mutants
      of roxy1 with repressors of AG, such as ap2 or lug. Glutaredoxins are
      oxidoreductases that oxidize or reduce conserved cysteine-containing motifs.
      Mutagenesis of conserved cysteines within the ROXY1 protein demonstrates the
      importance of cysteine 49 for its function. Our data demonstrate that,
      unexpectedly, a plant glutaredoxin is involved in flower development, probably by
      mediating post-translational modifications of target proteins required for normal
      petal organ initiation and morphogenesis.

PMID- 15728669
TI  - pitx3 defines an equivalence domain for lens and anterior pituitary placode.
AB  - Hedgehog signaling is required for formation and patterning of the anterior
      pituitary gland. However, the role of Hedgehog in pituitary precursor cell
      specification and subsequent placode formation is not well understood. We
      analyzed pituitary precursor cell lineages and find that pitx3 and distal-less3b
      (dlx3b) expression domains define lens and pituitary precursor positions. We show
      that pitx3 is required for pituitary pre-placode formation and cell
      specification, whereas dlx3b and dlx4b are required to restrict pituitary placode
      size. In smoothened mutant embryos that cannot transduce Hedgehog signals, median
      pituitary precursors are mis-specified and form an ectopic lens. Moreover,
      overexpression of sonic hedgehog (shh) blocks lens formation, and derivatives of
      lens precursors express genes characteristic of pituitary cells. However,
      overexpression of shh does not increase median pituitary placode size nor does it
      upregulate patched (ptc) expression in pituitary precursors during early
      somitogenesis. Our study suggests that by the end of gastrulation, pitx3
      expressing cells constitute an equivalence domain of cells that can form either
      pituitary or lens, and that a non-Hedgehog signal initially specifies this
      placodal field. During mid-somitogenesis, Hedgehog then acts on the established
      median placode as a necessary and sufficient signal to specify pituitary cell
      types.

PMID- 15728670
TI  - Peak levels of BMP in the Drosophila embryo control target genes by a feed
      forward mechanism.
AB  - Gradients of morphogens determine cell fates by specifying discrete thresholds of
      gene activities. In the Drosophila embryo, a BMP gradient subdivides the dorsal
      ectoderm into amnioserosa and dorsal epidermis, and also inhibits neuroectoderm
      formation. A number of genes are differentially expressed in response to the
      gradient, but how their borders of expression are established is not well
      understood. We present evidence that the BMP gradient, via the Smads, provides a
      two-fold input in regulating the amnioserosa-specific target genes such as Race.
      Peak levels of Smads in the presumptive amnioserosa set the expression domain of
      zen, and then Smads act in combination with Zen to directly activate Race. This
      situation resembles a feed-forward mechanism of transcriptional regulation. In
      addition, we demonstrate that ectopically expressed Zen can activate targets like
      Race in the presence of low level Smads, indicating that the role of the highest
      activity of the BMP gradient is to activate zen.

PMID- 15728671
TI  - Quail-duck chimeras reveal spatiotemporal plasticity in molecular and histogenic
      programs of cranial feather development.
AB  - The avian feather complex represents a vivid example of how a developmental
      module composed of highly integrated molecular and histogenic programs can become
      rapidly elaborated during the course of evolution. Mechanisms that facilitate
      this evolutionary diversification may involve the maintenance of plasticity in
      developmental processes that underlie feather morphogenesis. Feathers arise as
      discrete buds of mesenchyme and epithelium, which are two embryonic tissues that
      respectively form dermis and epidermis of the integument. Epithelial-mesenchymal
      signaling interactions generate feather buds that are neatly arrayed in space and
      time. The dermis provides spatiotemporal patterning information to the epidermis
      but precise cellular and molecular mechanisms for generating species-specific
      differences in feather pattern remain obscure. In the present study, we exploit
      the quail-duck chimeric system to test the extent to which the dermis regulates
      the expression of genes required for feather development. Quail and duck have
      distinct feather patterns and divergent growth rates, and we exchange pre
      migratory neural crest cells destined to form the craniofacial dermis between
      them. We find that donor dermis induces host epidermis to form feather buds
      according to the spatial pattern and timetable of the donor species by altering
      the expression of members and targets of the Bone Morphogenetic Protein, Sonic
      Hedgehog and Delta/Notch pathways. Overall, we demonstrate that there is a great
      deal of spatiotemporal plasticity inherent in the molecular and histogenic
      programs of feather development, a property that may have played a generative and
      regulatory role throughout the evolution of birds.

PMID- 15728672
TI  - The hedgehog-PKA pathway regulates two distinct steps of the differentiation of
      retinal ganglion cells: the cell-cycle exit of retinoblasts and their neuronal
      maturation.
AB  - In the developing zebrafish retina, neurogenesis is initiated in cells adjacent
      to the optic stalk and progresses to the entire neural retina. It has been
      reported that hedgehog (Hh) signalling mediates the progression of the
      differentiation of retinal ganglion cells (RGCs) in zebrafish. However, the
      progression of neurogenesis seems to be only mildly delayed by genetic or
      chemical blockade of the Hh signalling pathway. Here, we show that cAMP-dependent
      protein kinase (PKA) effectively inhibits the progression of retinal neurogenesis
      in zebrafish. Almost all retinal cells continue to proliferate when PKA is
      activated, suggesting that PKA inhibits the cell-cycle exit of retinoblasts. A
      cyclin-dependent kinase (cdk) inhibitor p27 inhibits the PKA-induced
      proliferation, suggesting that PKA functions upstream of cyclins and cdk
      inhibitors. Activation of the Wnt signalling pathway induces the
      hyperproliferation of retinal cells in zebrafish. The blockade of Wnt signalling
      inhibits the PKA-induced proliferation, but the activation of Wnt signalling
      promotes proliferation even in the absence of PKA activity. These observations
      suggest that PKA inhibits exit from the Wnt-mediated cell cycle rather than
      stimulates Wnt-mediated cell-cycle progression. PKA is an inhibitor of Hh
      signalling, and Hh signalling molecule morphants show severe defects in cell
      cycle exit of retinoblasts. Together, these data suggest that Hh acts as a short
      range signal to induce the cell-cycle exit of retinoblasts. The pulse inhibition
      of Hh signalling revealed that Hh signalling regulates at least two distinct
      steps of RGC differentiation: the cell-cycle exit of retinoblasts and RGC
      maturation. This dual requirement of Hh signalling in RGC differentiation implies
      that the regulation of a neurogenic wave is more complex in the zebrafish retina
      than in the Drosophila eye.

PMID- 15728673
TI  - The Drosophila trithorax group protein Kismet facilitates an early step in
      transcriptional elongation by RNA Polymerase II.
AB  - The Drosophila trithorax group gene kismet (kis) was identified in a screen for
      extragenic suppressors of Polycomb (Pc) and subsequently shown to play important
      roles in both segmentation and the determination of body segment identities. One
      of the two major proteins encoded by kis (KIS-L) is related to members of the
      SWI2/SNF2 and CHD families of ATP-dependent chromatin-remodeling factors. To
      clarify the role of KIS-L in gene expression, we examined its distribution on
      larval salivary gland polytene chromosomes. KIS-L is associated with virtually
      all sites of transcriptionally active chromatin in a pattern that largely
      overlaps that of RNA Polymerase II (Pol II). The levels of elongating Pol II and
      the elongation factors SPT6 and CHD1 are dramatically reduced on polytene
      chromosomes from kis mutant larvae. By contrast, the loss of KIS-L function does
      not affect the binding of PC to chromatin or the recruitment of Pol II to
      promoters. These data suggest that KIS-L facilitates an early step in
      transcriptional elongation by Pol II.

PMID- 15728674
TI  - Functional diversification of MYB23 and GL1 genes in trichome morphogenesis and
      initiation.
AB  - The functional diversification of duplicated genes is one of the driving forces
      in evolution. To understand the molecular mechanisms of gene diversification, we
      studied the functional relationship of the two Arabidopsis paralogous MYB-related
      genes GL1 and MYB23. We show that MYB23 controls trichome branching and trichome
      initiation at leaf edges. The latter is controlled redundantly together with GL1.
      We show that the two proteins are functionally equivalent during trichome
      initiation but not during trichome branching. RT-PCR and reporter construct
      analysis revealed spatial, temporal and genetic differences in transcriptional
      regulation of the GL1 and MYB23 genes. Presented data indicate that the
      diversification of GL1 and MYB23 gene functions occurred at the level of cis
      regulatory sequences with respect to trichome initiation, and that, in parallel,
      the diversification with respect to regulation of trichome branching also
      involved changes in respective proteins.

PMID- 15728675
TI  - Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical
      membrane of Drosophila photoreceptors.
AB  - In developing Drosophila photoreceptors, rhodopsin is trafficked to the
      rhabdomere, a specialized domain within the apical membrane surface. Rab11, a
      small GTPase implicated in membrane traffic, immunolocalizes to the trans-Golgi
      network, cytoplasmic vesicles and tubules, and the base of rhabdomeres. One hour
      after release from the endoplasmic reticulum, rhodopsin colocalizes with Rab11 in
      vesicles at the base of the rhabdomere. When Rab11 activity is reduced by three
      different genetic procedures, rhabdomere morphogenesis is inhibited and rhodopsin
      bearing vesicles proliferate within the cytosol. Rab11 activity is also essential
      for development of MVB endosomal compartments; this is probably a secondary
      consequence of impaired rhabdomere development. Furthermore, Rab11 is required
      for transport of TRP, another rhabdomeric protein, and for development of
      specialized membrane structures within Garland cells. These results establish a
      role for Rab11 in the post-Golgi transport of rhodopsin and of other proteins to
      the rhabdomeric membranes of photoreceptors, and in analogous transport processes
      in other cells.

PMID- 15728676
TI  - Inhibition of neurogenesis by SRp38, a neuroD-regulated RNA-binding protein.
AB  - Although serine-arginine rich (SR) proteins have often been implicated in the
      positive regulation of splicing, recent studies have shown that one unusual SR
      protein, SRp38, serves, contrastingly, as a splicing repressor during mitosis and
      stress response. We have identified a novel developmental role for SRp38 in the
      regulation of neural differentiation. SRp38 is expressed in the neural plate
      during embryogenesis and is transcriptionally induced by the neurogenic bHLH
      protein neuroD. Overexpression of SRp38 inhibits primary neuronal differentiation
      at a step between neurogenin and neuroD activity. This repression of neuronal
      differentiation requires activation of the Notch pathway. Conversely, depletion
      of SRp38 activity results in a dysregulation of neurogenesis. Finally, SRp38 can
      interact with the peptidyltransferase center of 28S rRNA, suggesting that SRp38
      activity may act, in part, via regulation of ribosome biogenesis or function.
      Strikingly, recent studies of several cell cycle regulators during primary
      neurogenesis have also revealed a crucial control step between neurogenin and
      neuroD. SRp38 may mediate one component of this control by maintaining splicing
      and translational silencing in undifferentiated neural cells.

PMID- 15728678
TI  - U.S. health spending projections for 2004-2014.
AB  - National health spending growth is anticipated to remain stable at just over 7.0
      percent through 2006, the result of diverging public- and private-sector spending
      trends. The faster public-sector spending growth is exemplified by the
      introduction of the new Medicare drug benefit in 2006. While this benefit is
      anticipated to have only a minor impact on overall health spending, it will
      result in a significant shift in funding from private payers and Medicaid to
      Medicare. By 2014, total health spending is projected to constitute 18.7 percent
      of gross domestic product, from 15.3 percent in 2003.

PMID- 15728677
TI  - Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body
      development.
AB  - Nectins are Ca2+-independent immunoglobulin-like cell-cell-adhesion molecules
      consisting of four members. Nectins homophilically and heterophilically trans
      interact to form a variety of cell-cell junctions, including cadherin-based
      adherens junctions in epithelial cells and fibroblasts in culture, synaptic
      junctions in neurons, and Sertoli cell-spermatid junctions in the testis, in
      cooperation with, or independently of, cadherins. To further explore the function
      of nectins, we generated nectin 1-/- and nectin 3-/-)mice. Both nectin 1-/- and
      nectin 3-/- mice showed a virtually identical ocular phenotype, microphthalmia,
      accompanied by a separation of the apex-apex contact between the pigment and non
      pigment cell layers of the ciliary epithelia. Immunofluorescence and
      immunoelectron microscopy revealed that nectin 1 and nectin 3, but not nectin 2,
      localized at the apex-apex junctions between the pigment and non-pigment cell
      layers of the ciliary epithelia. However, nectin 1-/- and nectin 3-/- mice showed
      no impairment of the apicolateral junctions between the pigment epithelia where
      nectin 1, nectin 2 and nectin 3 localized, or of the apicolateral junctions
      between the non-pigment epithelia where nectin 2 and nectin 3, but not nectin 1,
      localized. These results indicate that the heterophilic trans-interaction between
      nectin 1 and nectin 3 plays a sentinel role in establishing the apex-apex
      adhesion between the pigment and non-pigment cell layers of the ciliary epithelia
      that is essential for the morphogenesis of the ciliary body.

PMID- 15728679
TI  - Proprioceptive neuromuscular facilitation training induced alterations in muscle
      fibre type and cross sectional area.
AB  - OBJECTIVES: To compare the effects of proprioceptive neuromuscular facilitation
      (PNF) and isokinetic training on fibre type distribution and cross sectional area
      of the vastus lateralis muscle. METHODS: Twenty four male university students
      were divided into two equal groups: PNF training and isokinetic training (ISO).
      The training regimen for the PNF group consisted of three sets of 30 repetitions
      against maximal resistance, alternating two patterns of sequential movements of
      the right lower extremity: (a) toe flexion and ankle plantar flexion and
      eversion; (b) knee extension and hip extension, abduction, and internal rotation.
      The ISO group performed three sets of 30 repetitions alternating knee extension
      and flexion of the right leg at angular velocities of 180 and 90 degrees /s in an
      isokinetic dynamometer (Cybex). Both groups trained three times a week for a
      total of eight weeks. Muscle biopsy specimens were obtained from the right vastus
      lateralis muscle before and after training. RESULTS: The mean percentage area of
      type IIB fibre was significantly decreased (p<0.01) after eight weeks of PNF
      training, whereas that of type IIA fibre was significantly (p<0.05) increased.
      The mean percentage area of ISO trained type IIAB fibres exhibited an
      augmentative pattern (p<0.01) with a parallel reduction (p<0.05) in type IIA.
      Percentage fibre type distribution exhibited a similar pattern. CONCLUSIONS: Both
      PNF and ISO training alter fibre type distribution and mean cross sectional area.
      These changes occur in the type II fibre subgroup.

PMID- 15728680
TI  - Physical activity levels during phase IV cardiac rehabilitation in a group of
      male myocardial infarction patients.
AB  - OBJECTIVE: To determine physical activity levels during phase IV cardiac
      rehabilitation in 31 male myocardial infarction patients (median age 62, range 53
      77 years). METHODS: Patients recorded daily physical activity over 16 weeks in a
      diary. Diaries were analysed for total general physical activity (TGPA), leisure
      time physical activity (LTPA), and "active for life" exercise classes (AFL). Pre-
      and post-observation period (OP) subjects underwent a 10 m shuttle walking test
      (SWT) to determine changes in aerobic fitness. Rate of perceived exertion (RPE)
      determined exercise intensity. Estimated gross energy expenditure (EEE) was
      determined by a regression equation between RPE and Vo(2) (l min(-1)) during SWT.
      A total of 97% of subjects were on lipid lowering medication. RESULTS: There were
      no correlations between Vo(2) (l min(-1)) and body mass, therefore kcal min(-1)
      indicated activity intensity. There were no significant changes in physical
      activity patterns or in aerobic fitness. Estimated total LTPA (median 1376, range
      128-3380 kcal week(-1)) was less than that recommended to improve aerobic fitness
      and/or slow progression of coronary artery disease. Sixteen subjects attended a
      median of 29 (range 1-46) AFL during LTPA; one way ANOVA showed these subjects
      worked at greater EEE (AFL, n = 16, 6.6 (standard deviation 1.4) v no-AFL, n =
      15, 5.1 (1.8) EEE kcal min(-1), p = 0.017). CONCLUSION: Physical activity was
      stable, but patients' EEE appeared insufficient to improve aerobic fitness or
      slow progression of coronary artery disease. It was suggested that the promotion
      of LTPA and the availability of AFL classes should be reconsidered.

PMID- 15728681
TI  - Relation between foot arch index and ankle strength in elite gymnasts: a
      preliminary study.
AB  - BACKGROUND: Gymnasts usually start intensive training from early childhood. The
      impact of such strenuous training on the musculoskeletal system is not clear.
      OBJECTIVES: To evaluate the relation between muscle strength of the ankle joint
      and foot structure in gymnasts. METHODS: The study population comprised 20 high
      level male gymnasts and 17 non-athletic healthy male controls. Arch indices were
      measured using a podoscope. Ankle plantar/dorsiflexion and eversion/inversion
      strengths were measured using a Biodex 3 dynamometer within the protocol of
      concentric/concentric five repetitions at 30 degrees /s velocity. RESULTS: The
      mean arch index of the right and left foot of the gymnasts and the controls were
      respectively: 31.4 (29.1), 34.01 (34.65); 60.01 (30.3), 63.75 (32.27). Both the
      arch indices and the ankle dorsiflexion strengths were lower in the gymnasts.
      Although no correlation was found between strength and arch index in the control
      group, a significant correlation was observed between eversion strengths and arch
      indices of the gymnasts (r = 0.41, p = 0.02). CONCLUSIONS: Whether or not the
      findings indicate sport specific adaptation or less training of the ankle
      dorsiflexors, prospective data are required to elucidate the tendency for pes
      cavus in gymnasts, for whom stabilisation of the foot is a priority.

PMID- 15728682
TI  - Long term outcomes of inversion ankle injuries.
AB  - BACKGROUND: Ankle sprains are common sporting injuries generally believed to be
      benign and self limiting. However, some studies report a significant proportion
      of patients with ankle sprains having persistent symptoms for months or even
      years. AIMS: To determine the proportion of patients presenting to an Australian
      sports medicine clinic who had long term symptoms after a sports related
      inversion ankle sprain. METHODS: Consecutive patients referred to the NSW
      Institute of Sports Medicine from August 1999 to August 2002 with inversion ankle
      sprain were included. Exclusion criteria were fracture, ankle surgery, or
      concurrent lower limb problems. A control group, matched for age and sex, was
      recruited from patients attending the clinic for upper limb injuries in the same
      time period. Current ankle symptoms, ankle related disability, and current health
      status were ascertained through a structured telephone interview. RESULTS:
      Nineteen patients and matched controls were recruited and interviewed. The mean
      age in the ankle group was 20 (range 13-28). Twelve patients (63%) were male.
      Average follow up was 29 months. Only five (26%) ankle injured patients had
      recovered fully, with no pain, swelling, giving way, or weakness at follow up.
      None of the control group reported these symptoms (p<0.0001). Assessments of
      quality of life using short form-36 questionnaires (SF36) revealed a difference
      in the general health subscale between the two groups, favouring the control arm
      (p<0.05). There were no significant differences in the other SF36 subscales
      between the two groups. CONCLUSION: Most patients who sustained an inversion
      ankle injury at sport and who were subsequently referred to a sports medicine
      clinic had persistent symptoms for at least two years after their injury. This
      reinforces the importance of prevention and early effective treatment.

PMID- 15728683
TI  - Effect of sporting activity on absenteeism in a working population.
AB  - OBJECTIVES: To determine the effects of sporting activity on absenteeism in a
      working population. METHODS: Data were used from a prospective cohort study in a
      working population with a follow up period of 3 years and were collected with
      yearly questionnaires or collected from company records. Complete data on
      absenteeism, sporting activity, and potential confounders were collected for 1228
      workers. ANOVA was used to test differences in frequency and duration of
      absenteeism, correlations were computed to measure the association between number
      of sporting years (divided by age) and frequency and duration of absenteeism, and
      survival analysis, according to the Cox proportional hazards model, was used to
      test differences in relative risk at absenteeism and recovery. All analyses were
      adjusted for age, gender, smoking, and alcohol consumption, and were stratified
      for employees with sedentary and with more active jobs. RESULTS: ANOVA showed a
      statistically significant higher mean duration of absenteeism among employees not
      practicing sports, of approximately 20 days over a period of 4 years. The
      survival analysis showed an increased relative risk at absenteeism (relative risk
      (RR) 1.09; confidence interval (CI) 1.01 to 1.18) and a decreased relative risk
      at recovery (RR 0.90; CI 0.85 to 0.95) for employees not practicing sports. The
      effect of sporting activity is larger in employees with sedentary work. No
      associations were found between number of sporting years and absenteeism.
      CONCLUSION: Employees practicing sports take sick leave significantly less often
      than their colleagues not practicing sports, while their periods of sick leave
      are shorter, especially when their work is sedentary.

PMID- 15728684
TI  - Multiple osteochondroses and avulsion fracture of anterior superior iliac spine
      in a soccer player.
AB  - Apophysitis describes a chronic traction injury at the insertion site of a
      tendon. There is a gradual onset of pain with no clear history of injury. Without
      adequate preventive methods, an avulsion fracture may result. The case is here
      reported of an apophyseal avulsion fracture of the anterior superior iliac spine
      in an adolescent caused by playing football before the end of treatment for
      apophysitis. An open reduction and internal fixation was performed followed by a
      rehabilitation programme. No complications occurred, and the patient had returned
      to his previous level of sporting activity after six weeks.

PMID- 15728685
TI  - "Tomber dans les pommes" - can head injury cause brain damage?

PMID- 15728686
TI  - The power of placebo.

PMID- 15728687
TI  - Return to play guidelines after anterior cruciate ligament surgery.

PMID- 15728688
TI  - Effectiveness of extracorporeal shock wave therapy for tennis elbow (lateral
      epicondylitis).
AB  - Randomised controlled trials were reviewed to evaluate the evidence of the
      effectiveness of extracorporeal shock wave therapy in the management of tennis
      elbow. Seven relevant trials were found, which had satisfactory methodology but
      conflicting results. Further research with well designed randomised control
      trials is needed to establish the absolute and relative effectiveness of this
      intervention for tennis elbow.

PMID- 15728690
TI  - Biological risk indicators for recurrent non-specific low back pain in
      adolescents.
AB  - OBJECTIVES: A matched case-control study was carried out to evaluate biological
      risk indicators for recurrent non-specific low back pain in adolescents. METHODS:
      Adolescents with recurrent non-specific low back pain (symptomatic; n = 28; mean
      (SD) age 14.9 (0.7) years) and matched controls (asymptomatic; n = 28; age 14.9
      (0.7) years) with no history of non-specific low back pain participated. Measures
      of stature, mass, sitting height, sexual maturity (Tanner self assessment),
      lateral flexion of the spine, lumbar sagittal plane mobility (modified Schober),
      hip range of motion (Leighton flexometer), back and hamstring flexibility (sit
      and reach), and trunk muscle endurance (number of sit ups) were performed using
      standardised procedures with established reliability. Backward stepwise logistic
      regression analysis was performed, with the presence/absence of recurrent low
      back pain as the dependent variable and the biological measures as the
      independent variables. RESULTS: Hip range of motion, trunk muscle endurance,
      lumbar sagittal plane mobility, and lateral flexion of the spine were identified
      as significant risk indicators of recurrent low back pain (p<0.05). Follow up
      analysis indicated that symptomatic subjects had significantly reduced lateral
      flexion of the spine, lumbar sagittal plane mobility, and trunk muscle endurance
      (p<0.05). CONCLUSIONS: Hip range of motion, abdominal muscle endurance, lumbar
      flexibility, and lateral flexion of the spine were risk indicators for recurrent
      non-specific low back pain in a group of adolescents. These risk indicators
      identify the potential for exercise as a primary or secondary prevention method.

PMID- 15728691
TI  - Participation in leanness sports but not training volume is associated with
      menstrual dysfunction: a national survey of 1276 elite athletes and controls.
AB  - OBJECTIVE: To examine the prevalence of menstrual dysfunction in the total
      population of Norwegian elite female athletes and national representative
      controls in the same age group. METHODS: A detailed questionnaire that included
      questions on training and/or physical activity patterns, menstrual, dietary, and
      weight history, oral contraceptive use, and eating disorder inventory subtests
      was administered to all elite female athletes representing the country at the
      junior or senior level (aged 13-39 years, n = 938) and national representative
      controls in the same age group (n = 900). After exclusion, a total of 669
      athletes (88.3%) and 607 controls (70.2%) completed the questionnaire
      satisfactorily. RESULTS: Age at menarche was significantly (p<0.001) later in
      athletes (13.4 (1.4) years) than in controls (13.0 (1.3) years), and differed
      among sport groups. A higher percentage of athletes (7.3%) than controls (2.0%)
      reported a history of primary amenorrhoea (p<0.001). A similar percentage of
      athletes (16.5%) and controls (15.2%) reported present menstrual dysfunction, but
      a higher percentage of athletes competing in leanness sports reported present
      menstrual dysfunction (24.8%) than athletes competing in non-leanness sports
      (13.1%) (p<0.01) and controls (p<0.05). CONCLUSIONS: These novel data include
      virtually all eligible elite athletes, and thus substantially extend previous
      studies. Age at menarche occurred later and the prevalence of primary amenorrhoea
      was higher in elite athletes than in controls. A higher percentage of athletes
      competing in sports that emphasise thinness and/or a specific weight reported
      present menstrual dysfunction than athletes competing in sports focusing less on
      such factors and controls. On the basis of a comparison with a previous study,
      the prevalence of menstrual dysfunction was lower in 2003 than in 1993.

PMID- 15728692
TI  - Individual variation in the erythropoietic response to altitude training in elite
      junior swimmers.
AB  - OBJECTIVES: Inter-individual variations in sea level performance after altitude
      training have been attributed, at least in part, to an inter-individual
      variability in hypoxia induced erythropoiesis. The aim of the present study was
      to examine whether the variability in the increase in total haemoglobin mass
      after training at moderate altitude could be predicted by the erythropoietin
      response after 4 h exposure to normobaric hypoxia at an ambient Po(2)
      corresponding to the training altitude. METHODS: Erythropoietin levels were
      measured in 16 elite junior swimmers before and after 4 h exposure to normobaric
      hypoxia (Fio(2) 0.15, approximately 2500 m) as well as repeatedly during 3 week
      altitude training (2100-2300 m). Before and after the altitude training, total
      haemoglobin mass (CO rebreathing) and performance in a stepwise increasing
      swimming test were determined. RESULTS: The erythropoietin increase (10-185%)
      after 4 h exposure to normobaric hypoxia showed considerable inter-individual
      variation and was significantly (p<0.001) correlated with the acute
      erythropoietin increase during altitude training but not with the change in total
      haemoglobin mass (significant increase of approximately 6% on average). The
      change in sea level performance after altitude training was not related to the
      change in total haemoglobin mass. CONCLUSIONS: The results of the present
      prospective study confirmed the wide inter-individual variability in
      erythropoietic response to altitude training in elite athletes. However, their
      erythropoietin response to acute altitude exposure might not identify those
      athletes who respond to altitude training with an increase in total haemoglobin
      mass.

PMID- 15728693
TI  - High bone mineral density in loaded skeletal regions of former professional
      football (soccer) players: what is the effect of time after active career?
AB  - OBJECTIVES: Physical exercise is an important factor in the acceleration and
      maintenance of bone mineral density (BMD). Football is an impact loading sport
      and some studies demonstrate its site specific, bone mass increasing effect. We
      compared BMD at different skeletal regions in a group of former professional
      football players and in normal control subjects and evaluated the effect of
      demographic factors and time after active career on BMD. METHODS: Twenty four
      former football players <70 years old who had retired from professional football
      at least 10 years previously and 25 non-athletic controls were recruited. The
      demographic characteristics, activity levels, and dietary habits of all subjects
      and the chronological history of the footballers' professional careers were
      noted. BMD was measured by DEXA at the calcaneus and distal tibia and at the
      lumbar spine, proximal femur, and distal and proximal radius, and compared
      between groups. Stepwise multiple linear regression analysis was used to
      determine the probable predictors of BMD in former football players. RESULTS: In
      former players BMD values were found to be significantly higher at the lumbar
      spine, femur neck, femur trochanter, distal tibia, and calcaneus, but not at
      Ward's triangle (femur) or the distal and proximal radius regions compared with
      controls. Time after active career was the only independent predictor of BMD at
      the lumbar spine, proximal femur (neck, trochanter, and Ward's triangle), and
      distal tibia. CONCLUSIONS: Former footballers had higher BMD at weight loaded
      sites and time after active career seemed to be an important factor in
      determining BMD.

PMID- 15728695
TI  - Does changing the configuration of a motor racing circuit make it safer?
AB  - OBJECTIVES: To assess the pattern of injuries presenting to a racing circuit
      medical centre in two three-year periods before and after two chicanes were built
      into the track. METHODS: Medical centre records were used to identify all
      patients assessed during the two time periods. Those referred to hospital were
      categorised by injury severity into three groups. RESULTS: The proportions of
      those attending the medical centre that were referred and admitted to hospital
      were the same in both periods (12-13% and 3% respectively). During the two study
      periods, the risk of a severe injury for a car driver decreased from 0.1% to
      0.03% (p<0.05). For a motorcyclist, similar values were 0% and 0.2% (not
      significant). CONCLUSIONS: Chicanes have improved the safety of the racing
      circuit for car drivers, reducing the risk of injury.

PMID- 15728696
TI  - Diffusely increased bone scintigraphic uptake in patellofemoral pain syndrome.
AB  - OBJECTIVES: Painful disorders of the patellofemoral joint are one of the most
      frequent complaints in orthopaedic and sports medicine. The aims of this study
      were to determine whether bone scintigrams of patients suffering from
      patellofemoral pain syndrome (PFPS) show diffuse uptake and in what bony
      compartment of the knee uptake, if any, was localised. METHODS: Fifty eight
      patients with chronic PFPS were examined. All patients underwent a detailed
      clinical history and a thorough physical examination of the knee. Anterior and
      lateral static images of both knees were made using a gamma camera 3 h after
      injection of 550 MBq of (99m)Tc-HMDP. Two experienced radiologists visually
      evaluated the scans blindly and separately. As 51 patients had bilateral pain,
      109 painful knees are included in the results. RESULTS: Diffuse uptake on bone
      scintigrams was found in 48 knees in 30 of the patients. In 33 knees the uptake
      was localised to only one bone compartment, in 10 knees diffuse uptake was found
      in two of the bones forming the knee joint, and in six knees all three bone
      compartments (the distal femur, the patella, and the proximal tibia) exhibited
      diffuse uptake. CONCLUSIONS: Scintigrams of approximately half of the patients
      with PFPS will show diffuse uptake in one or more of the bony compartments of the
      knee joint and radioactive tracer accumulation will occur as often in the
      proximal tibia as in the patella.

PMID- 15728698
TI  - Enhancing the efficacy of the 20 m multistage shuttle run test.
AB  - OBJECTIVE: Maximal oxygen uptake (Vo(2max)) of 44 ml kg(-1) min(-1) is an
      accepted criterion (Vo(2CR)) below which health and fitness for young male adults
      may be compromised. New algorithms validated for Vo(2CR) screening using the 20 m
      multistage shuttle run test (20mMST) were developed. METHODS: Vo(2max) was
      assessed in 110 males using a stationary gas analyser in a treadmill test (TT)
      and in 40 of these subjects using a portable gas analyser in the 20mMST. Vo(2max)
      predicted from the 20mMST in 70 subjects was used for cross validation. Two
      equations predicting Vo(2max) during 20mMST (EQ(MST)) and TT (EQ(TT)) were
      developed. RESULTS: Significant energy cost variance (EC(V)) was detected between
      TT and 20mMST (p<0.001), correlated significantly with subject height, and was a
      significant predictor of Vo(2max) differences between TT and 20mMST. The r(2) of
      EQ(MST) was 0.92 (p<0.001). Predicted Vo(2max) values from EQ(MST) correlated
      with directly measured 20mMST Vo(2max) at r = 0.96 (p<0.001). ANOVA detected no
      mean difference (p>0.05) between predicted and measured values. Prevalence of low
      fitness based on Vo(2CR) was 0.37. McNemar chi(2) indicated significant
      differences in sensitivity (p<0.001) and specificity (p<0.05) between the
      original 20mMST equation (EQ(LEG)) and EQ(TT), regarding Vo(2CR) screening.
      Cohen's kappa demonstrated higher agreement with TT Vo(2max) for EQ(TT) (p<0.001)
      than EQ(LEG) (p<0.05). TT Vo(2max) correlated with the end result of both EQ(LEG)
      and EQ(TT) at r = 0.75 (p<0.001). Unlike EQ(TT) (p>0.05), mean predicted Vo(2max)
      from EQ(LEG) was significantly higher compared to TT Vo(2max) (p<0.001).
      CONCLUSION: These algorithms increase the efficacy of 20mMST to accurately
      evaluate aspects of health and fitness.

PMID- 15728700
TI  - Quantification of the weakness and fatigue in thoracic outlet syndrome with
      isokinetic measurements.
AB  - OBJECTIVES: Patients with thoracic outlet syndrome (TOS) complain of many
      subjective symptoms that are difficult to measure and quantify. In this study we
      have tried to assess the weakness (muscle strength) and fatigue (endurance) of
      these patients with an objective measurement method, isokinetic muscle testing.
      METHODS: Twenty three TOS patients and 15 age matched healthy controls were
      enrolled in the study. Detailed histories of the patients were taken and the
      patients underwent complete physical examinations. Cervical radiographies,
      Doppler ultrasonography, electromyography, and isokinetic measurements were
      carried out. The isokinetic measurements were carried using the Biodex System 3
      dynamometer during concentric shoulder flexions and extensions at velocities of
      60 degrees /s, 180 degrees /s, and 240 degrees /s. RESULTS: Although the muscle
      strengths of both groups seemed to be similar, the fatigue ratios of TOS patients
      at 60 degrees /s and 180 degrees /s were found to be higher compared with those
      of healthy controls (p = 0.029, p = 0.007). CONCLUSIONS: TOS patients were found
      to have muscular performance similar to controls, but their upper extremities
      developed fatigue more easily than those of healthy individuals.

PMID- 15728701
TI  - Quadriceps assessment in professional soccer players.

PMID- 15728699
TI  - Does prolonged cycling of moderate intensity affect immune cell function?
AB  - BACKGROUND: Prolonged exercise may induce temporary immunosuppression with a
      presumed increased susceptibility for infection. However, there are only few data
      on immune cell function after prolonged cycling at moderate intensities typical
      for road cycling training sessions. METHODS: The present study examined the
      influence on immune cell function of 4 h of cycling at a constant intensity of
      70% of the individual anaerobic threshold. Interleukin-6 (IL-6) and C-reactive
      protein (CRP), leukocyte and lymphocyte populations, activities of natural killer
      (NK), neutrophils, and monocytes were examined before and after exercise, and
      also on a control day without exercise. RESULTS: Cycling for 4 h induced a
      moderate acute phase response with increases in IL-6 from 1.0 (SD 0.5) before to
      9.6 (5.6) pg/ml 1 h after exercise and CRP from 0.5 (SD 0.4) before to 1.8 (1.3)
      mg/l 1 day after exercise. Although absolute numbers of circulating NK cells,
      monocytes, and neutrophils increased during exercise, on a per cell basis NK cell
      activity, neutrophil and monocyte phagocytosis, and monocyte oxidative burst did
      not significantly change after exercise. However, a minor effect over time for
      neutrophil oxidative burst was noted, tending to decrease after exercise.
      CONCLUSIONS: Prolonged cycling at moderate intensities does not seem to seriously
      alter the function of cells of the first line of defence. Therefore, the
      influence of a single typical road cycling training session on the immune system
      is only moderate and appears to be safe from an immunological point of view.

PMID- 15728702
TI  - Prenatal exposure to phthalates and intrauterine inflammation: a unifying
      hypothesis.

PMID- 15728703
TI  - Inhibitory effects of vitamin A on TCDD-induced cytochrome P-450 1A1 enzyme
      activity and expression.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an extremely potent environmental
      contaminant that produces a wide range of adverse biological effects, including
      the induction of cytochrome P450 1A1(CYP1A1) that may enhance the toxic effects
      of TCDD. Several studies indicated that concurrent supplementation of vitamin A
      could reduce the toxicity, and potentially inhibit CYP1A1 activity (measured as
      ethoxyresorufin-O-deethylase [EROD] activity). In the present study, we
      investigated the in vivo effects of vitamin A on EROD activities and the
      expression of CYP1A1 in the liver of TCDD-treated mice. In Experiment I, the mice
      were given a single oral dose of 40 mug TCDD/kg body weight with or without the
      continuous administration of 2500 IU vitamin A/kg body weight/day, and were
      killed on day 1, 3, 7, 14, or 28. In Experiment II, the mice were given daily an
      oral dose of 0.1 mug TCDD/kg body weight with or without supplement of 2000 IU
      vitamin A/kg body weight, and were killed on day 14, 28, or 42. In both
      experiments, TCDD caused liver damage and increase in relative liver weights,
      augmented the EROD activities and CYP1A1 expression, and increased the aryl
      hydrocarbon receptor (AhR) mRNA expression, but did not alter the AhR nuclear
      translocator (ARNT) mRNA expression. CYP1A1 mRNA expression and AhR mRNA
      expression showed a similar time course. The liver damage in TCDD + vitamin A
      treated mice was less severe than that in TCDD-treated mice. EROD activities,
      CYP1A1 expression, and AhR mRNA expression in vitamin A + TCDD-treated mice were
      lower than those in TCDD-treated mice, indicating that supplementation of vitamin
      A might attenuate the liver damage caused by TCDD.

PMID- 15728704
TI  - Apoptosis in stages of mouse hepatocarcinogenesis: failure to counterbalance cell
      proliferation and to account for strain differences in tumor susceptibility.
AB  - C3H/He and B6C3F1 show much higher liver cancer susceptibility than C57BL/6J
      mice. We studied the hypothesis that this difference might result from failure of
      apoptosis. Hepatocarcinogenesis was induced by a single dose of N
      nitrosodiethylamine (NDEA), followed by phenobarbital (PB) for up to 90 weeks. We
      observed (1) earlier appearance of putative preneoplastic foci (PPF),
      hepatocellular adenoma (HCA), and carcinoma (HCC) in C3H/He than in C57Bl/6J mice
      and (2) an increase of hepatocellular DNA synthesis in C3H/He and C57Bl/6J mice,
      compared to normal liver, via PPF and HCA to HCC. PB enhanced DNA synthesis and
      growth of PPF, in the C3H/He strain only, and of HCA and HCC of both strains.
      Apoptoses were rare in unaltered livers as well as in preneoplastic lesions, but
      tended to increase in HCA and HCC of both strains. PB lowered apoptotic activity
      in PPF of C3H/He mice, but enhanced it in HCA and HCC of C57Bl/6J mice at late
      stages. In conclusion, the strain difference in growth rates of PPF and tumors is
      largely determined by higher rates of cell proliferation in C3H/He mice, with and
      without promotion by PB. Moreover, in C57Bl/6J mice the promoting effect of PB
      was restricted to HCA and HCC and was not seen in PPF. Apoptosis was generally
      low and was not a major cause of the strain difference in tumor susceptibility.
      In contrast with rat liver, inhibition of apoptosis appears to be a minor
      determinant of tumor promotion in mice.

PMID- 15728705
TI  - No increase of apoptosis in regressing mouse liver after withdrawal of growth
      stimuli or food restriction.
AB  - In short-term in vivo experiments, liver growth and regression in mice with high
      (C3H/He), intermediate (B6C3F1) or low (C57BL/6J) susceptibility to
      hepatocarcinogenesis was compared. Liver growth was induced by dietary
      administration of phenobarbital (PB; 750 ppm) or nafenopin (NAF; 500 ppm). PB or
      NAF treatment for 7 days produced moderate increases of liver DNA (15% or 25-28%,
      respectively) along with pronounced hypertrophy. Liver growth was strongest in
      C3H/He mice. Cessation of PB or NAF treatment led to a rapid regression of liver
      hypertrophy. However, the enhanced hepatic DNA content persisted for at least 2
      weeks in all mouse strains. Apoptosis was not increased at any time after
      cessation of treatment in all strains. Food restriction to 60% of the ad libitum
      intake did not amplify either regression of liver hyperplasia or the occurrence
      of apoptosis. No strain difference in the occurrence of apoptosis was detected.
      Mouse hepatocytes in liver regressing after mitogen withdrawal do not enter
      apoptosis as readily as rat hepatocytes.

PMID- 15728706
TI  - Precision-cut liver slices as a new model to study toxicity-induced hepatic
      stellate cell activation in a physiologic milieu.
AB  - Hepatic stellate cell (HSC) activation is a key event in the natural process of
      wound healing as well as in fibrosis development in liver. Current in vitro
      models for HSC activation contribute significantly to the understanding of HSC
      biology and fibrogenesis but still fall far short of recapitulating in vivo
      intercellular functional and anatomic relationships. In addition, when cultured
      on uncoated plastic, HSC spontaneously activate, which makes HSC activation
      difficult to regulate or analyze. We have examined whether the use of precision
      cut liver slices might overcome these limitations. Liver slices (8 mm diameter,
      250 microm thickness) were generated from normal rat liver and incubated for 3 or
      16 h with increasing doses of carbon tetrachloride (CCl4). Rat liver slices
      remained viable during incubation, as shown by minimal enzyme leakage. Expression
      of markers for HSC activation and the onset of fibrogenesis in the liver slices
      was studied using real-time PCR and Western blotting. In unstimulated liver
      slices, mRNA and protein levels of desmin, heat shock protein 47, and alpha B
      crystallin remained constant, indicating quiescence of HSC, whereas Kruppel-like
      factor 6 expression was increased. In contrast, incubation with CCl4 led to a
      time- and dose-dependent increase in mRNA expression of all markers and an
      increased alpha B-crystallin protein expression. In conclusion, we have developed
      a technique to induce activation of quiescent HSC in rat liver slices. This model
      permits the study of toxicity-induced HSC activation within a physiological
      milieu, not only in animal but ultimately also in human tissue, and could
      contribute to the reduction of animal experiments.

PMID- 15728707
TI  - Is myosin light-chain phosphorylation a regulatory signal for the osmotic
      activation of the Na+-K+-2Cl- cotransporter?
AB  - Myosin light-chain (MLC) kinase (MLCK)-dependent increase in MLC phosphorylation
      has been proposed to be a key mediator of the hyperosmotic activation of the Na+
      K+-2Cl- cotransporter (NKCC). To address this hypothesis and to assess whether
      MLC phosphorylation plays a signaling or permissive role in NKCC regulation, we
      used pharmacological and genetic means to manipulate MLCK, MLC phosphorylation,
      or myosin ATPase activity and followed the impact of these alterations on the
      hypertonic stimulation of NKCC in porcine kidney tubular LLC-PK1 epithelial
      cells. We found that the MLCK inhibitor ML-7 suppressed NKCC activity
      independently of MLC phosphorylation. Notably, ML-7 reduced both basal and
      hypertonically stimulated NKCC activity without influencing MLC phosphorylation
      under these conditions, and it inhibited NKCC activation by Cl- depletion, a
      treatment that did not increase MLC phosphorylation. Furthermore, prevention of
      the osmotically induced increase in MLC phosphorylation by viral induction of
      cells with a nonphosphorylatable, dominant negative MLC mutant (AA-MLC) did not
      affect the hypertonic activation of NKCC. Conversely, a constitutively active MLC
      mutant (DD-MLC) that mimics the diphosphorylated form neither stimulated isotonic
      nor potentiated hypertonic NKCC activity. Furthermore, a depolarization-induced
      increase in endogenous MLC phosphorylation failed to activate NKCC. However,
      complete abolition of basal MLC phosphorylation by K252a or the inhibition of
      myosin ATPase by blebbistatin significantly reduced the osmotic stimulation of
      NKCC without suppressing its basal or Cl- depletion-triggered activity. These
      results indicate that an increase in MLC phosphorylation is neither a sufficient
      nor a necessary signal to stimulate NKCC in tubular cells. However, basal myosin
      activity plays a permissive role in the optimal osmotic responsiveness of NKCC.

PMID- 15728708
TI  - LPA2 receptor mediates mitogenic signals in human colon cancer cells.
AB  - Lysophosphatidic acid (LPA) is a mediator of multiple cellular responses. LPA
      mediates its effects predominantly through the G protein-coupled receptors LPA1,
      LPA2, and LPA3. In the present work, we studied LPA2-mediated signaling using
      human colon cancer cell lines, which predominantly express LPA2. LPA2 activated
      Akt and Erk1/2 in response to LPA. LPA mediated Akt activation was inhibited by
      pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a
      blocker of phospholipase Cbeta, U-73122. LPA also induced interleukin-8 (IL-8)
      synthesis in the colon cancer cells by primarily activating LPA2 receptor. We
      also found that LPA2 interacts with Na+/H+ exchanger regulatory factor 2
      (NHERF2). Activation of Akt and Erk1/2 was significantly attenuated by silencing
      of NHERF2 expression by RNA interference, suggesting a pivotal role of NHERF2 in
      LPA2-mediated signaling. We found that expression of LPA2 was elevated, whereas
      expression of LPA1 downregulated in several types of cancers, including ovarian
      and colon cancer. We conclude that LPA2 is the major LPA receptor in colon cancer
      cells and cellular signals by LPA2 are largely mediated through its ability to
      interact with NHERF2.

PMID- 15728709
TI  - Matrix metalloproteinases mediate beta-adrenergic receptor-stimulated apoptosis
      in adult rat ventricular myocytes.
AB  - Changes in the synthesis and activity of matrix metalloproteinases (MMPs) and
      their inhibitors (TIMPs) are associated with myocardial remodeling. Here we
      measured the expression and activity of MMPs and TIMPs, and tested the hypothesis
      that increased MMP activity plays a proapoptotic role in beta-adrenergic receptor
      (beta-AR)-stimulated apoptosis of adult rat ventricular myocytes (ARVMs). beta-AR
      stimulation (isoproterenol, 24 h) increased mRNA levels of MMP-2 and TIMP-1 while
      it decreased TIMP-2 mRNA levels as analyzed by real-time PCR. Western blot
      analysis, immunocytochemical analysis, in-gel zymography, and MMP-2 activity
      assay confirmed beta-AR-stimulated increases in MMP-2 protein levels and
      activity. Inhibition of MMPs using GM-6001 (a broad-spectrum inhibitor of MMPs),
      SB3CT (inhibitor of MMP-2), and purified TIMP-2 inhibited beta-AR-stimulated
      apoptosis as determined by TdT-mediated dUTP nick end labeling staining.
      Treatment with active MMP-2 alone increased the number of apoptotic cells. This
      increase in MMP-2-mediated apoptosis was inhibited by GM-6001 and SB3CT
      pretreatment. Coimmunoprecipitation studies indicated increased physical
      association of MMP-2 with beta1-integrins after beta-AR stimulation. Inhibition
      of MMP-2 using SB3CT or stimulation of beta1-integrin signaling using laminin
      inhibited the increased association of MMP-2 with beta1-integrins. beta-AR
      stimulation increased poly-ADP-ribose-polymerase cleavage, which was inhibited by
      inhibition of MMP-2. These data suggest the following: 1) beta-AR stimulation
      increases MMP-2 expression and activity and inhibits TIMP-2 expression; 2)
      inhibition of MMPs, most likely MMP-2, inhibits beta-AR-stimulated apoptosis; and
      3) the apoptotic effects of MMP-2 may be mediated, at least in part, via its
      interaction with beta1 integrins and poly-ADP-ribose-polymerase cleavage.

PMID- 15728710
TI  - Influence of increased mechanical loading by hypergravity on the microtubule
      cytoskeleton and prostaglandin E2 release in primary osteoblasts.
AB  - Cells respond to a wide range of mechanical stimuli such as fluid shear and
      strain, although the contribution of gravity to cell structure and function is
      not understood. We hypothesized that bone-forming osteoblasts are sensitive to
      increased mechanical loading by hypergravity. A centrifuge suitable for cell
      culture was developed and validated, and then primary cultures of fetal rat
      calvarial osteoblasts at various stages of differentiation were mechanically
      loaded using hypergravity. We measured microtubule network morphology as well as
      release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts,
      a stimulus of 10x gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased
      microtubule network height 1.12-fold without affecting cell viability.
      Hypergravity (3 h) caused dose-dependent (5-50 g) increases in PGE2 (5.3-fold at
      50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2
      release depended on duration but not orientation of the hypergravity load. As
      osteoblasts differentiated, sensitivity to hypergravity declined. We conclude
      that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to
      gravitational loading, which appears to be blunted in mature osteoblasts.

PMID- 15728712
TI  - Water and solute permeability of rat lung caveolae: high permeabilities explained
      by acyl chain unsaturation.
AB  - Caveolae are invaginated membrane structures with high levels of cholesterol,
      sphingomyelin, and caveolin protein that are predicted to exist as liquid-ordered
      domains with low water permeability. We isolated a caveolae-enriched membrane
      fraction without detergents from rat lung and characterized its permeability
      properties to nonelectrolytes and protons. Membrane permeability to water was
      2.85 +/- 0.41 x 10(-3) cm/s, a value 5-10 times higher than expected based on
      comparisons with other cholesterol and sphingolipid-enriched membranes.
      Permeabilities to urea, ammonia, and protons were measured and found to be
      moderately high for urea and ammonia at 8.85 +/- 2.40 x 10(-7)and 6.84 +/- 1.03 x
      10(-2) respectively and high for protons at 8.84 +/- 3.06 x 10(-2) cm/s. To
      examine whether caveolin or other integral membrane proteins were responsible for
      high permeabilities, liposomes designed to mimic the lipids of the inner and
      outer leaflets of the caveolar membrane were made. Osmotic water permeability to
      both liposome compositions were determined and a combined inner/outer leaflet
      water permeability was calculated and found to be close to that of native
      caveolae at 1.58 +/- 1.1 x 10(-3) cm/s. In caveolae, activation energy for water
      flux was high (19.4 kcal/mol) and water permeability was not inhibited by HgCl2;
      however, aquaporin 1 was detectable by immunoblotting. Immunostaining of rat lung
      with AQP1 and caveolin antisera revealed very low levels of colocalization. We
      conclude that aquaporin water channels do not contribute significantly to the
      observed water flux and that caveolae have relatively high water and solute
      permeabilities due to the high degree of unsaturation in their fatty acyl chains.

PMID- 15728713
TI  - Mechanism and regulation of human intestinal niacin uptake.
AB  - The mechanism of uptake of dietary niacin (nicotinic acid) by intestinal
      epithelial cells is not well understood, and nothing is known about regulation of
      the uptake process. In this investigation, we used human-derived intestinal
      epithelial Caco-2 cells and purified intestinal brush-border membrane vesicles
      (BBMVs) isolated from human organ donors to assess niacin uptake. Our findings
      show niacin uptake by Caco-2 cells to be 1) temperature and energy dependent; 2)
      Na+ independent, but highly dependent on extracellular acidic pH; 3) saturable as
      a function of concentration, with an apparent K(m) of 0.53 +/- 0.08 microM; 4)
      severely inhibited by the membrane-impermeable sulfhydryl group of reagents; and
      5) highly specific for niacin but not affected by monocarboxylic acids. A marked
      trans stimulation in [3H]niacin efflux from preloaded Caco-2 cells by unlabeled
      niacin in the incubation buffer was also observed. These findings suggest the
      involvement of a specialized, pH-dependent, carrier-mediated mechanism for human
      intestinal niacin uptake. This suggestion was confirmed in studies with native
      human intestinal BBMVs. We also examined possible regulation of niacin uptake by
      Caco-2 cells via specific intracellular regulatory pathways. The results show
      that while the PKA-, PKC-, and Ca2+/calmodulin-mediated regulatory pathways play
      no role in regulating niacin uptake, a role for a protein tyrosine kinase (PTK)
      mediated pathway is apparent. The results of these studies show for the first
      time the existence of a specialized, acidic pH-dependent, carrier-mediated system
      of niacin uptake by human intestinal epithelial cells that operates at the
      micromolar (physiological) range of niacin. The results also suggest the possible
      involvement of a PTK-mediated pathway in the regulation of niacin uptake.

PMID- 15728711
TI  - ATP stimulates GRK-3 phosphorylation and beta-arrestin-2-dependent
      internalization of P2X7 receptor.
AB  - The objective of this study was to understand the mechanisms involved in P2X(7)
      receptor activation. Treatments with ATP or with the P2X(7) receptor-specific
      ligand 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) induced pore
      formation, but the effect was slower in CaSki cells expressing endogenous P2X(7)
      receptor than in human embryonic kidney (HEK)-293 cells expressing exogenous
      P2X(7) receptor (HEK-293-hP2X(7)-R). In both types of cells Western blots
      revealed expression of three forms of the receptor: the functional 85-kDa form
      present mainly in the membrane and 65- and 18-kDa forms expressed in both the
      plasma membrane and the cytosol. Treatments with ATP transiently decreased the 85
      kDa form and increased the 18-kDa form in the membrane, suggesting
      internalization, degradation, and recycling of the receptor. In CaSki cells ATP
      stimulated phosphorylation of the 85-kDa form on tyrosine and serine residues.
      Phosphorylation on threonine residues increased with added ATP, and it increased
      ATP requirements for phosphorylation on tyrosine and serine residues, suggesting
      a dominant-negative effect. In both CaSki and in HEK-293-hP2X(7)-R cells ATP also
      increased binding of the 85-kDa form to G protein-coupled receptor kinase (GRK)
      3, beta-arrestin-2, and dynamin, and it stimulated beta-arrestin-2 redistribution
      into submembranous regions of the cell. These results suggest a novel mechanism
      for P2X(7) receptor action, whereby activation involves a GRK-3-, beta-arrestin-2
      , and dynamin-dependent internalization of the receptor into clathrin domains,
      followed in part by receptor degradation as well as receptor recycling into the
      plasma membrane.

PMID- 15728714
TI  - Pro- and anti-inflammatory substances modulate expression of the leukotriene B4
      receptor, BLT1, in human monocytes.
AB  - The high-affinity leukotriene B(4) (LTB(4)) receptor, BLT1, is a chemotactic
      receptor involved in inflammatory responses. In this study, we have explored the
      regulation of BLT1 expression in human monocytes by pro- and anti-inflammatory
      cytokines, lipopolysaccharide (LPS), and dexamethasone. We found that
      proinflammatory mediators, such as interferon-gamma (IFN-gamma), tumor necrosis
      factor-alpha, and LPS, down-regulated expression, whereas the anti-inflammatory
      cytokine, interleukin-10, and dexamethasone up-regulated BLT1 mRNA expression.
      The effect of IFN-gamma on BLT1 mRNA expression was rapidly detectable (<4 h) and
      concentration-dependent (1-50 ng/ml) and seems to be exerted through a block in
      transcriptional activity. Alterations in mRNA expression were accompanied by
      changes in BLT1 surface expression, and receptor down-modulation following IFN
      gamma stimulation resulted in a diminished chemotactic response to LTB(4). The
      regulation of BLT1 mRNA and receptor protein expression was similar to the
      regulation of the monocyte chemoattractant protein-1 chemokine receptor, CC
      chemokine recptor 2 (CCR2). Flow cytometric analysis of fresh peripheral blood
      cells revealed that classical (CD14(++)CD16(-)) monocytes express high levels of
      BLT1 and CCR2 and that both receptors are down-regulated on CD14(+)CD16(+)
      monocytes. Apart from providing insight into the regulation of BLT1 in human
      monocytes, our results reveal a parallel expression and regulation of BLT1 and
      CCR2, which may help to understand monocyte trafficking during pathophysiological
      conditions.

PMID- 15728715
TI  - The nature of the phagosomal membrane: endoplasmic reticulum versus plasmalemma.
AB  - For decades, the vacuole that surrounds particles engulfed by phagocytosis was
      believed to originate from the plasma membrane. Conversion of the nascent
      phagosome into a microbicidal organelle was thought to result from the
      subsequent, orderly fusion of early endosomes, late endosomes, and ultimately,
      lysosomes with the original plasma membrane-derived vacuole. This conventional
      model has been challenged, if not superseded, by a revolutionary model that
      regards phagosome formation as resulting from the particle sliding into the
      endoplasmic reticulum via an opening at the base of the phagocytic cup. The
      merits and implications of these two hypotheses are summarized here and analyzed
      in light of recent results.

PMID- 15728716
TI  - Stimulation of P2X receptors enhances lipooligosaccharide-mediated apoptosis of
      endothelial cells.
AB  - Exposure of endothelial cells to lipid A-containing molecules, such as
      lipopolysaccharide (LPS) or lipooligosaccharide (LOS), causes the release of
      purinergic compounds [e.g., adenosine 5'-triphosphate (ATP)] and can lead to
      apoptosis. The P2X family of purinergic receptors (e.g., P2X(7)) has been
      reported to modulate LPS signaling events and to participate in apoptosis. We
      investigated the role that P2X receptors play in the apoptosis that follows
      exposure of bovine endothelial cells to Haemophilus somnus LOS. Addition of P2X
      inhibitors, such as periodate-oxidized ATP (oATP) or pyridoxal-phosphate-6
      azophenyl-2',4'-disulfonic acid tetrasodium, significantly reduced LOS-induced
      apoptosis. Incubation of endothelial cells with apyrase, which degrades ATP,
      diminished LOS-induced apoptosis of endothelial cells. Concomitant addition of
      P2X agonists [e.g., 2',3'-(4-benzoyl)-benzoyl ATP or ATP] to LOS-treated
      endothelial cells significantly enhanced caspase-3 activation. The P2X antagonist
      oATP significantly blocked caspase-8 but not caspase-9 activation in LOS-treated
      endothelial cells. Together, these data indicate that stimulation of P2X
      receptors enhances LOS-induced apoptosis of endothelial cells, possibly as a
      result of endogenous release of ATP, which results in caspase-8 activation.

PMID- 15728717
TI  - Inhibition of IL-18 reduces myeloperoxidase activity and prevents edema in
      intestine following alcohol and burn injury.
AB  - Previous studies have shown that alcohol (EtOH) ingestion before burn injury
      impaired intestinal barrier and immune function. This study determined whether
      EtOH and burn injury up-regulate interleukin (IL)-18 and whether IL-18 up
      regulation following EtOH and burn injury is a cause for neutrophil recruitment
      and increased intestinal edema. Rats (250 g) were gavaged with EtOH to achieve a
      blood EtOH level in the range of 100 mg/dL prior to burn or sham injury (25%
      total body surface area). A group of rats was treated with Ac-YVAD-CHO (5 mg/kg),
      an inhibitor of caspase-1 (an enzyme that converts pro-IL-18, an inactive form of
      IL-18, to mature IL-18), at the time of injury. One day after injury, rats were
      killed. IL-18 production was determined in circulation and in the supernatants
      harvested from spleen, mesenteric lymph nodes, and Peyer's patch cell cultures as
      well as in intestinal tissue homogenates. Neutrophil accumulation in intestine
      was determined by measuring myeloperoxidase (MPO) activity. We found a
      significant increase in IL-18 levels in the lymphoid cell supernatants and
      intestinal tissue homogenates obtained from EtOH and burn-injured rats compared
      with the rats receiving burn or sham injury. This was accompanied by an increase
      in intestinal MPO and edema. No demonstrable change in intestinal morphology was
      observed in any group. Treatment of rats with caspase-1 inhibitor significantly
      attenuated the increase in IL-18 levels and intestinal MPO activity in EtOH and
      burn-injured rats. Inhibition of IL-18 also prevented an increase in intestinal
      tissue water content. As MPO is considered an index of neutrophil infiltration,
      results presented in this manuscript collectively suggest that IL-18 up
      regulation is likely to contribute to the increased neutrophil infiltration and
      edema in intestinal tissue observed following EtOH and burn injury.

PMID- 15728718
TI  - Lysophosphatidylcholine-induced surface redistribution regulates signaling of the
      murine G protein-coupled receptor G2A.
AB  - Intracellular trafficking and spatial dynamics of membrane receptors critically
      regulate receptor function. Using microscopic and subcellular fractionation
      analysis, we studied the localization of the murine G protein-coupled receptor
      G2A (muG2A). Evaluating green fluorescent protein-tagged, exogenously expressed
      as well as the endogenous muG2A, we observed that this receptor was spontaneously
      internalized and accumulated in endosomal compartments, whereas its surface
      expression was enhanced and stabilized by lysophosphatidylcholine (LPC)
      treatment. Monensin, a general inhibitor of recycling pathways, blocked LPC
      regulated surface localization of muG2A as well as muG2A-dependent extracellular
      signal-regulated kinase (ERK) activation and cell migration induced by LPC
      treatment. Mutation of the conserved DRY motif (R-->A) enhanced the surface
      expression of muG2A, resulting in its resistance to monensin inhibition of ERK
      activation. Our data suggest that intracellular sequestration and surface
      expression regulated by LPC, rather than direct agonistic activity control the
      signaling responses of murine G2A toward LPC.

PMID- 15728719
TI  - A mutation in dVps28 reveals a link between a subunit of the endosomal sorting
      complex required for transport-I complex and the actin cytoskeleton in
      Drosophila.
AB  - Proteins that constitute the endosomal sorting complex required for transport
      (ESCRT) are necessary for the sorting of proteins into multivesicular bodies
      (MVBs) and the budding of several enveloped viruses, including HIV-1. The first
      of these complexes, ESCRT-I, consists of three proteins: Vps28p, Vps37p, and
      Vps23p or Tsg101 in mammals. Here, we characterize a mutation in the Drosophila
      homolog of vps28. The dVps28 gene is essential: homozygous mutants die at the
      transition from the first to second instar. Removal of maternally contributed
      dVps28 causes early embryonic lethality. In such embryos lacking dVps28, several
      processes that require the actin cytoskeleton are perturbed, including axial
      migration of nuclei, formation of transient furrows during cortical divisions in
      syncytial embryos, and the subsequent cellularization. Defects in actin
      cytoskeleton organization also become apparent during sperm individualization in
      dVps28 mutant testis. Because dVps28 mutant cells contained MVBs, these defects
      are unlikely to be a secondary consequence of disrupted MVB formation and suggest
      an interaction between the actin cytoskeleton and endosomal membranes in
      Drosophila embryos earlier than previously appreciated.

PMID- 15728720
TI  - Dissociation of the Nuf2-Ndc80 complex releases centromeres from the spindle-pole
      body during meiotic prophase in fission yeast.
AB  - In the fission yeast Schizosaccharomyces pombe, centromeres remain clustered at
      the spindle-pole body (SPB) during mitotic interphase. In contrast, during
      meiotic prophase centromeres dissociate from the SPB. Here we examined the
      behavior of centromere proteins in living meiotic cells of S. pombe. We show that
      the Nuf2-Ndc80 complex proteins (Nuf2, Ndc80, Spc24, and Spc25) disappear from
      the centromere in meiotic prophase when the centromeres are separated from the
      SPB. The centromere protein Mis12 also dissociates during meiotic prophase;
      however, Mis6 remains throughout meiosis. When cells are induced to meiosis by
      inactivation of Pat1 kinase (a key negative regulator of meiosis), centromeres
      remain associated with the SPB during meiotic prophase. However, inactivation of
      Nuf2 by a mutation causes the release of centromeres from the SPB in pat1 mutant
      cells, suggesting that the Nuf2-Ndc80 complex connects centromeres to the SPB. We
      further found that removal of the Nuf2-Ndc80 complex from the centromere and
      centromere-SPB dissociation are caused by mating pheromone signaling. Because
      pat1 mutant cells also show aberrant chromosome segregation in the first meiotic
      division and this aberration is compensated by mating pheromone signaling,
      dissociation of the Nuf2-Ndc80 complex may be associated with remodeling of the
      kinetochore for meiotic chromosome segregation.

PMID- 15728721
TI  - Specialization of the HOG pathway and its impact on differentiation and virulence
      of Cryptococcus neoformans.
AB  - The human pathogenic fungus Cryptococcus neoformans has diverged from a common
      ancestor into three biologically distinct varieties or sibling species over the
      past 10-40 million years. During evolution of these divergent forms, serotype A
      C. neoformans var. grubii has emerged as the most virulent and cosmopolitan
      pathogenic clade. Therefore, understanding how serotype A C. neoformans is
      distinguished from less successful pathogenic serotypes will provide insights
      into the evolution of fungal virulence. Here we report that the structurally
      conserved Pbs2-Hog1 MAP kinase cascade has been specifically recruited as a
      global regulator to control morphological differentiation and virulence factors
      in the highly virulent serotype A H99 clinical isolate, but not in the laboratory
      generated and less virulent serotype D strain JEC21. The mechanisms of Hog1
      regulation are strikingly different between the two strains, and the
      phosphorylation kinetics and localization pattern of Hog1 are opposite in H99
      compared with JEC21 and other yeasts. The unique Hog1 regulatory pattern observed
      in the H99 clinical isolate is widespread in serotype A strains and is also
      present in some clinical serotype D isolates. Serotype A hog1delta and pbs2delta
      mutants are attenuated in virulence, further underscoring the role of the Pbs2
      Hog1 MAPK cascade in the pathogenesis of cryptococcosis.

PMID- 15728723
TI  - Actin depolymerization transduces the strength of B-cell receptor stimulation.
AB  - Polymerization of the actin cytoskeleton has been found to be essential for B
      cell activation. We show here, however, that stimulation of BCR induces a rapid
      global actin depolymerization in a BCR signal strength-dependent manner, followed
      by polarized actin repolymerization. Depolymerization of actin enhances and
      blocking actin depolymerization inhibits BCR signaling, leading to altered BCR
      and lipid raft clustering, ERK activation, and transcription factor activation.
      Furthermore actin depolymerization by itself induces altered lipid raft
      clustering and ERK activation, suggesting that F-actin may play a role in
      separating lipid rafts and in setting the threshold for cellular activation.

PMID- 15728722
TI  - Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and
      Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor
      stimulated PC12 cells.
AB  - Neurite outgrowth is an important process in the formation of neuronal networks.
      Rac1 and Cdc42, members of the Rho-family GTPases, positively regulate neurite
      extension through reorganization of the actin cytoskeleton. Here, we examine the
      dynamic linkage between Rac1/Cdc42 and phosphatidylinositol 3-kinase (PI3-kinase)
      during nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells.
      Activity imaging using fluorescence resonance energy transfer probes showed that
      PI3-kinase as well as Rac1/Cdc42 was transiently activated in broad areas of the
      cell periphery immediately after NGF addition. Subsequently, local and repetitive
      activation of PI3-kinase and Rac1/Cdc42 was observed at the protruding sites.
      Depletion of Vav2 and Vav3 by RNA interference significantly inhibited both
      Rac1/Cdc42 activation and the formation of short processes leading to neurite
      outgrowth. At the NGF-induced protrusions, local phosphatidylinositol 3,4,5
      trisphosphate accumulation recruited Vav2 and Vav3 to activate Rac1 and Cdc42,
      and conversely, Vav2 and Vav3 were required for the local activation of PI3
      kinase. These observations demonstrated for the first time that Vav2 and Vav3 are
      essential constituents of the positive feedback loop that is comprised of PI3
      kinase and Rac1/Cdc42 and cycles locally with morphological changes.

PMID- 15728724
TI  - A Dictyostelium homologue of WASP is required for polarized F-actin assembly
      during chemotaxis.
AB  - The actin cytoskeleton controls the overall structure of cells and is highly
      polarized in chemotaxing cells, with F-actin assembled predominantly in the
      anterior leading edge and to a lesser degree in the cell's posterior. Wiskott
      Aldrich syndrome protein (WASP) has emerged as a central player in controlling
      actin polymerization. We have investigated WASP function and its regulation in
      chemotaxing Dictyostelium cells and demonstrated the specific and essential role
      of WASP in organizing polarized F-actin assembly in chemotaxing cells. Cells
      expressing very low levels of WASP show reduced F-actin levels and significant
      defects in polarized F-actin assembly, resulting in an inability to establish
      axial polarity during chemotaxis. GFP-WASP preferentially localizes at the
      leading edge and uropod of chemotaxing cells and the B domain of WASP is required
      for the localization of WASP. We demonstrated that the B domain binds to
      PI(4,5)P2 and PI(3,4,5)P3 with similar affinities. The interaction between the B
      domain and PI(3,4,5)P3 plays an important role for the localization of WASP to
      the leading edge in chemotaxing cells. Our results suggest that the spatial and
      temporal control of WASP localization and activation is essential for the
      regulation of directional motility.

PMID- 15728725
TI  - Identification of functionally interacting SNAREs by using complementary
      substitutions in the conserved '0' layer.
AB  - Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
      complexes form bundles of four parallel alpha-helices. The central '0' layer of
      interacting amino acid side chains is highly conserved and contains one arginine
      and three glutamines, leading to the classification of SNAREs into R, Qa, Qb, and
      Qc-SNAREs. Replacing one of the glutamines with arginine in the yeast exocytotic
      SNARE complex is either lethal or causes a conditional growth defect that is
      compensated by replacing the R-SNARE arginine with glutamine. Using the yeast
      SNARE complex mediating traffic from the endoplasmic reticulum to the Golgi
      apparatus, we now show that functionally interacting SNAREs can be mapped by
      systematically exchanging glutamines and arginines in the '0' layer. The Q-->R
      replacement in the Qb-SNARE Bos1p has the strongest effect and can be alleviated
      by an Q-->R replacement in the R-SNARE Sec22p. Four Q residues in the central
      layer caused growth defects above 30 degrees C that were rescued by Q-->R
      substitutions in the Qa and Qc SNAREs Sed5p and Bet1p, respectively. The
      sec22(Q)/sed5(R) mutant is temperature sensitive and is rescued by a compensating
      R-->Q replacement in the R-SNARE Ykt6p. This rescue is attributed to the
      involvement of Sed5p and Ykt6p in a different SNARE complex that functions in
      intra-Golgi trafficking.

PMID- 15728726
TI  - Identification and characterization of a novel alpha-kinase with a von Willebrand
      factor A-like motif localized to the contractile vacuole and Golgi complex in
      Dictyostelium discoideum.
AB  - We have identified a new protein kinase in Dictyostelium discoideum that carries
      the same conserved class of "alpha-kinase" catalytic domain as reported
      previously in myosin heavy chain kinases (MHCKs) in this amoeba but that has a
      completely novel domain organization. The protein contains an N-terminal von
      Willebrand factor A (vWFA)-like motif and is therefore named VwkA. Manipulation
      of VwkA expression level via high copy number plasmids (VwkA++ cells) or gene
      disruption (vwkA null cells) results in an array of cellular defects, including
      impaired growth and multinucleation in suspension culture, impaired development,
      and alterations in myosin II abundance and assembly. Despite sequence similarity
      to MHCKs, the purified protein failed to phosphorylate myosin II in vitro.
      Autophosphorylation activity, however, was enhanced by calcium/calmodulin, and
      the enzyme can be precipitated from cellular lysates with calmodulin-agarose,
      suggesting that VwkA may directly bind calmodulin. VwkA is cytosolic in
      distribution but enriched on the membranes of the contractile vacuole and Golgi
      like structures in the cell. We propose that VwkA likely acts indirectly to
      influence myosin II abundance and assembly behavior and possibly has broader
      roles than previously characterized alpha kinases in this organism, which all
      seem to be MHCKs.

PMID- 15728727
TI  - Delineation of a unique protein-protein interaction site on the surface of the
      estrogen receptor.
AB  - Recent studies have identified a series of estrogen receptor (ER)-interacting
      peptides that recognize sites that are distinct from the classic coregulator
      recruitment (AF2) region. Here, we report the structural and functional
      characterization of an ERalpha-specific peptide that binds to the liganded
      receptor in an AF2-independent manner. The 2-A crystal structure of the
      ER/peptide complex reveals a binding site that is centered on a shallow
      depression on the beta-hairpin face of the ligand-binding domain. The peptide
      binds in an unusual extended conformation and makes multiple contacts with the
      ligand-binding domain. The location and architecture of the binding site provides
      an insight into the peptide's ER subtype specificity and ligand interaction
      preferences. In vivo, an engineered coactivator containing the peptide motif is
      able to strongly enhance the transcriptional activity of liganded ERalpha,
      particularly in the presence of 4-hydroxytamoxifen. Furthermore, disruption of
      this binding surface alters ER's response to the coregulator TIF2. Together,
      these results indicate that this previously unknown interaction site represents a
      bona fide control surface involved in regulating receptor activity.

PMID- 15728728
TI  - HLA-restricted epitope identification and detection of functional T cell
      responses by using MHC-peptide and costimulatory microarrays.
AB  - Identification of T cell epitopes is a vital but often slow and difficult step in
      studying the immune response to infectious agents and autoantigens. We report a
      spatially addressable technique for screening large numbers of T cell epitopes
      for both specific antigen recognition and functional activity induced. This
      system uses microarrays of immobilized, recombinant MHC-peptide complexes,
      costimulatory molecules, and cytokine-capture antibodies. The array elements act
      as synthetic antigen-presenting cells and specifically elicit T cell responses,
      including adhesion, secretion of cytokines, and modulation of surface markers.
      The method allows facile identification of pertinent T cell epitopes in a large
      number of candidates and simultaneous determination of the functional outcome of
      the interaction. Using this method, we have characterized the activation of human
      CD4(+) and CD8(+) T cells responding to vaccinia, influenza, HIV-1, and Epstein
      Barr viruses.

PMID- 15728729
TI  - A mouse model for study of systemic HIV-1 infection, antiviral immune responses,
      and neuroinvasiveness.
AB  - We created a model of HIV-1 infection of conventional mice for investigation of
      viral replication, control, and pathogenesis. To target HIV-1 to mice, the coding
      region of gp120 in HIV-1/NL4-3 was replaced with that of gp80 from ecotropic
      murine leukemia virus, a retrovirus that infects only rodents. The resulting
      chimeric virus construct, EcoHIV, productively infected murine lymphocytes, but
      not human lymphocytes, in culture. Adult, immunocompetent mice were readily
      susceptible to infection by a single inoculation of EcoHIV as shown by detection
      of virus in splenic lymphocytes, peritoneal macrophages, and the brain. The virus
      produced in animals was infectious, as shown by passage in culture, and
      immunogenic, as shown by induction of antibodies to HIV-1 Gag and Tat. A second
      chimeric virus based on clade D HIV-1/NDK was also highly infectious in mice; it
      was detected in both spleen and brain 3 wk after tail vein inoculation, and it
      induced expression of infection response genes, MCP-1, STAT1, IL-1beta, and
      complement component C3, in brain tissue as determined by quantitative real-time
      PCR. EcoHIV infection of mice forms a useful model of HIV-1 infection of human
      beings for convenient and safe investigation of HIV-1 therapy, vaccines, and
      potentially pathogenesis.

PMID- 15728730
TI  - Effect of centrally administered C75, a fatty acid synthase inhibitor, on ghrelin
      secretion and its downstream effects.
AB  - The central administration of the fatty acid synthase (FAS) inhibitor, C75,
      rapidly suppresses the expression of orexigenic neuropeptides [neuropeptide Y
      (NPY) and agouti-related protein (AgRP)] and activates expression of anorexigenic
      neuropeptides [proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated
      transcript (CART)] in the hypothalamus. The combined actions of these changes
      inhibit food intake and decrease body weight. Intracerebroventricular injection
      of C75 appears to rapidly inhibit the secretion of ghrelin by hypothalamic
      explants ex vivo and by the stomach in vivo. Ghrelin administered
      intracerebroventricularly reverses the anorexic effect of C75, suggesting that
      C75 acts upstream of ghrelin. Because ghrelin-producing neurons are known to form
      synapses onto NPY/AgRP neurons, we suggest that the reversal of C75-induced
      anorexia by ghrelin may be mediated by NPY/AgRP neurons. This hypothesis is
      supported by the finding that ghrelin reverses the C75-induced inactivation
      (assessed by c-Fos expression) of neurons in the arcuate nucleus that express NPY
      (assessed by immunohistochemical costaining). These effects closely correlate
      with appropriate changes downstream in the expression of the hypothalamic
      neuropeptides that regulate feeding behavior, i.e., down-regulation of the
      expression of NPY and AgRP and up-regulation of the expression of
      proopiomelanocortin/alpha-melanocyte-stimulating hormone, provoked by C75 and
      reversed by ghrelin. We propose a model in which ghrelin secretion plays an
      intermediary role between malonyl-CoA, the substrate of fatty acid synthase, and
      the neural circuitry regulating energy homeostasis.

PMID- 15728731
TI  - Weak selection revealed by the whole-genome comparison of the X chromosome and
      autosomes of human and chimpanzee.
AB  - The effect of weak selection driving genome evolution has attracted much
      attention in the last decade, but the task of measuring the strength of such
      selection is particularly difficult. A useful approach is to contrast the
      evolution of X-linked and autosomal genes in two closely related species in a
      whole-genome analysis. If the fitness effect of mutations is recessive, X-linked
      genes should evolve more rapidly than autosomal genes when the mutations are
      advantageous, and they should evolve more slowly than autosomal genes when the
      mutations are deleterious. We found synonymous substitutions on the X chromosome
      of human and chimpanzee to be less frequent than those on the autosomes. When
      calibrated against substitutions in the intergenic regions and pseudogenes to
      filter out the differences in the mutation rate and ancestral population size
      between X chromosomes and autosomes, X-linked synonymous substitutions are still
      10% less frequent. At least 90% of the synonymous substitutions in human and
      chimpanzee are estimated to be deleterious, but the fitness effect is weaker than
      the effect of genetic drift. However, X-linked nonsynonymous substitutions are
      approximately 30% more frequent than autosomal ones, suggesting the fixation of
      advantageous mutations that are recessive.

PMID- 15728732
TI  - Inhibition of NUDEL (nuclear distribution element-like)-oligopeptidase activity
      by disrupted-in-schizophrenia 1.
AB  - Recently, nuclear distribution element-like (NUDEL) has been implicated to play a
      role in lissencephaly and schizophrenia through interactions with the
      lissencephaly gene 1 (Lis1) and disrupted-in-schizophrenia 1 (DISC1) products,
      respectively. Interestingly, NUDEL is the same protein as endooligopeptidase A
      (EOPA), a thiol-activated peptidase involved in conversion and inactivation of a
      number of bioactive peptides. In this study, we have cloned EOPA from the human
      brain and have confirmed that it is equivalent to NUDEL, leading us to suggest a
      single name, NUDEL-oligopeptidase. In the brain, the monomeric form of NUDEL
      oligopeptidase is responsible for the peptidase activity whose catalytic
      mechanism is likely to involve a reactive cysteine, because mutation of Cys-273
      fully abolished NUDEL-oligopeptidase activity without disrupting the protein's
      secondary structure. Cys-273 is very close to the DISC1-binding site on NUDEL
      oligopeptidase. Intriguingly, DISC1 inhibits NUDEL-oligopeptidase activity in a
      competitive fashion. We suggest that the activity of NUDEL-oligopeptidase is
      under tight regulation through protein-protein interactions and that disruption
      of these interactions, as postulated in a Scottish DISC1 translocation
      schizophrenia cohort, may lead to aberrant regulation of NUDEL-oligopeptidase,
      perhaps providing a substrate for the pathology of schizophrenia.

PMID- 15728733
TI  - Intranasal administration of nerve growth factor (NGF) rescues recognition memory
      deficits in AD11 anti-NGF transgenic mice.
AB  - Nerve growth factor (NGF) delivery to the brain of patients appears to be an
      emerging potential therapeutic approach to neurodegenerative disease, such as
      Alzheimer's disease (AD). The intranasal route of administration could provide an
      alternative to intracere-broventricular infusion and gene therapy. We previously
      showed that intranasal administration of NGF determined an amelioration of
      cholinergic deficit and a decrease in the number of phosphotau-positive neurons
      and of beta-amyloid accumulation in AD11 mice, which express transgenic
      antibodies neutralizing NGF action and exhibit a progressive Alzheimer-like
      neurodegeneration. In this study, we report that the Alzheimer-like
      neurodegeneration in AD11 mice is linked to progressive behavioral deficits in
      visual recognition memory and spatial memory starting from 4 months of age. To
      establish whether intranasal administration of NGF, started after the appearance
      of the first memory deficits, could revert the cognitive deficits in AD11 mice,
      we assessed the performance of NGF-treated or control AD11 mice in the object
      recognition test and in a test of memory for place and context. Deficits
      exhibited by untreated AD11 mice could be rescued by the intranasal
      administration of NGF. Thus, this route of administration provides a promising
      way to deliver NGF to the brain in a therapeutic perspective.

PMID- 15728734
TI  - On the role of Cro in lambda prophage induction.
AB  - The lysogenic state of bacteriophage lambda is exceptionally stable yet the
      prophage is readily induced in response to DNA damage. This delicate epigenetic
      switch is believed to be regulated by two proteins; the lysogenic maintenance
      promoting protein CI and the early lytic protein Cro. First, we confirm, in the
      native configuration, the previous observation that the DNA loop mediated by
      oligomerization of CI bound to two distinct operator regions (O(L) and O(R)),
      increases repression of the early lytic promoters and is important for stable
      maintenance of lysogeny. Second, we show that the presence of the cro gene might
      be unimportant for the lysogenic to lytic switch during induction of the lambda
      prophage. We revisit the idea that Cro's primary role in induction is instead to
      mediate weak repression of the early lytic promoters.

PMID- 15728735
TI  - Development without germ cells: the role of the germ line in zebrafish sex
      differentiation.
AB  - The progenitors of the gametes, the primordial germ cells (PGCs) are typically
      specified early in the development in positions, which are distinct from the
      gonad. These cells then migrate toward the gonad where they differentiate into
      sperms and eggs. Here, we study the role of the germ cells in somatic development
      and particularly the role of the germ line in the sex differentiation in
      zebrafish. To this end, we ablated the germ cells using two independent methods
      and followed the development of the experimental fish. First, PGCs were ablated
      by knocking down the function of dead end, a gene important for the survival of
      this lineage. Second, a method to eliminate the PGCs using the toxin-antitoxin
      components of the parD bacterial genetic system was used. Specifically, we
      expressed a bacterial toxin Kid preferentially in the PGCs and at the same time
      protected somatic cells by uniformly expressing the specific antidote Kis. Our
      results demonstrate an unexpected role for the germ line in promoting female
      development because PGC-ablated fish invariably developed as males.

PMID- 15728736
TI  - Expression of N-acetylglucosamine 6-O-sulfotransferases (GlcNAc6STs)-1 and -4 in
      human monocytes: GlcNAc6ST-1 is implicated in the generation of the 6-sulfo N
      acetyllactosamine/Lewis x epitope on CD44 and is induced by TNF-alpha.
AB  - Sulfation at the 6-O position of N-acetylglucosamine (GlcNAc) in the context of
      sialyl 6-sulfo Lewis x occurs constitutively on specific glycoproteins present on
      high-walled endothelial venules (HEV) and is important for L-selectin dependent
      homing of lymphocytes. Here, the proinflammatory cytokine, TNF-alpha, induced the
      expression of 6-sulfo N-acetyllactosamine (LacNAc)/Lewis x on human peripheral
      blood monocytes (PBM). This epitope was detected by monoclonal antibody (mAb)
      AG107 after neuraminidase treatment suggesting a sialylated epitope, which was
      present on the cell adhesion molecule, CD44. Treatment of human PBM with TNF
      alpha up-regulated the expression of N-acetylglucosamine 6-O-sulfotransferase-1
      (GlcNAc6ST-1) and GlcNAc6ST-4, as determined by reverse transcriptase polymerase
      chain reaction (RT-PCR). However, only GlcNAc6ST-1 was induced by TNF-alpha in
      the human SR91 cell line, which also up-regulated the AG107 epitope. In ECV304
      cells, the expression of GlcNAc6ST-4 alone was insufficient to generate the AG107
      epitope. However, the transfection of GlcNAc6ST-1 resulted in significant sulfate
      incorporation into CD44 and generated the 6-sulfo LacNAc/Lewis x epitope on CD44,
      which was present largely on N-linked glycans. This demonstrates the induction of
      GlcNAc6STs in human monocytes in response to TNF-alpha and implicates GlcNAc6ST-1
      in the generation of the 6-sulfo LacNAc/Lewis x epitope on CD44.

PMID- 15728737
TI  - GC composition of the human genome: in search of isochores.
AB  - The isochore theory, proposed nearly three decades ago, depicts the mammalian
      genome as a mosaic of long, fairly homogeneous genomic regions that are
      characterized by their guanine and cytosine (GC) content. The human genome, for
      instance, was claimed to consist of five distinct isochore families: L1, L2, H1,
      H2, and H3, with GC contents of <37%, 37%-42%, 42%-47%, 47%-52%, and >52%,
      respectively. In this paper, we address the question of the validity of the
      isochore theory through a rigorous sequence-based analysis of the human genome.
      Toward this end, we adopt a set of six attributes that are generally claimed to
      characterize isochores and statistically test their veracity against the
      available draft sequence of the complete human genome. By the selection criteria
      used in this study: distinctiveness, homogeneity, and minimal length of 300 kb,
      we identify 1,857 genomic segments that warrant the label "isochore." These
      putative isochores are nonuniformly scattered throughout the genome and cover
      about 41% of the human genome. We found that a four-family model of putative
      isochores is the most parsimonious multi-Gaussian model that can be fitted to the
      empirical data. These families, however, are GC poor, with mean GC contents of
      35%, 38%, 41%, and 48% and do not resemble the five isochore families in the
      literature. Moreover, due to large overlaps among the families, it is impossible
      to classify genomic segments into isochore families reliably, according to
      compositional properties alone. These findings undermine the utility of the
      isochore theory and seem to indicate that the theory may have reached the limits
      of its usefulness as a description of genomic compositional structures.

PMID- 15728738
TI  - Adaptive evolution of the insulin gene in caviomorph rodents.
AB  - Insulin is a conservative molecule among mammals, maintaining both its structure
      and function. Rodents that belong to the Suborder Hystricognathi represent an
      exception, having a very divergent molecule with unusual physiological
      properties. In this work, we analyzed the evolutionary pattern of the insulin
      gene in caviomorph rodents (South American hystricomorph rodents). We found that
      these rodents have higher rates of nonsynonymous:synonymous substitutions
      (d(N)/d(S)) than nonhystricomorph rodents and that values are heterogeneous
      inside the group. We estimated codons under positive selection, specifically the
      second binding site (A13 and B17) and others related with hexamerization (B18,
      B20, and B22). In the monomer structure, all selected sites formed a single patch
      around the second binding site. In the hexamer structure, these amino acids were
      grouped into three major patches. In this structure, contacts between B chains
      involved all selected sites (except B18), and between faces in the center of the
      molecule, all contacts were among selected sites. While there is no clear
      hypothesis regarding the cause of this drastic change, experimental evidence does
      show that this group of rodents has some peculiarities in growth function, and,
      whether coincidental or not, these changes appeared together with important
      changes in life-history traits.

PMID- 15728739
TI  - Prefrontal cortical norepinephrine release is critical for morphine-induced
      reward, reinstatement and dopamine release in the nucleus accumbens.
AB  - Increasing evidence suggests that in addition to the mesoaccumbens dopamine (DA)
      system other neurotransmitter and brain systems are also involved in opiate
      addiction. Recent evidence points to a major involvement of brain norepinephrine
      (NE) in the behavioral and central effects of opiates and, more specifically,
      indicates that NE in the prefrontal cortex may have a critical role in rewarding
      effects of opiates. Moreover, a body of data points to regions within the medial
      prefrontal cortex (mpFC) acting as final common pathway of drug relapse behavior.
      The present experiments were aimed at investigating the possibility of a
      selective involvement of the prefrontal cortical NE in the rewarding and
      reinstating effects of morphine. In a first set of experiments, we found that
      morphine enhances NE and DA release in the mpFC and DA release in the nucleus
      accumbens, as measured by intra-cerebral microdialysis. Selective depletion of
      medial prefrontal cortical noradrenergic afferents abolished the morphine-induced
      increase in DA release in the nucleus accumbens. In a second series of
      experiments, we demonstrated that the same lesion impaired both conditioned place
      preference (CPP) induced by morphine and reinstatement of an extinguished CPP.
      The present results indicate that an intact prefrontal cortical NE transmission
      is necessary for morphine-induced rewarding effects, reinstatement, and
      mesoaccumbens dopamine release.

PMID- 15728740
TI  - Domain-general and domain-sensitive prefrontal mechanisms for recollecting events
      and detecting novelty.
AB  - Recollecting the past and discriminating novel from familiar memoranda depend on
      poorly understood prefrontal cortical (PFC) mechanisms hypothesized to vary
      according to memory task (e.g. recollection versus novelty detection) and domain
      of targeted memories (e.g. perceptual versus conceptual). Using event-related
      fMRI, we demonstrate that recollecting conceptual or perceptual details
      surrounding object encounters similarly recruits left frontopolar and posterior
      PFC compared with detecting novel stimuli, suggesting that a domain-general
      control network is engaged during contextual remembering. In contrast, left
      anterior ventrolateral PFC coactivated with a left middle temporal region
      associated with semantic representation, and right ventrolateral PFC with
      bilateral occipito-temporal cortices associated with representing object form,
      depending on whether recollections were conceptual or perceptual. These
      PFC/posterior cortical dissociations suggest that during recollection,
      lateralized ventrolateral PFC mechanisms bias posterior conceptual or perceptual
      feature representations as a function of memory relevance, potentially improving
      the gain of bottom-up memory signals. Supporting this domain-sensitive biasing
      hypothesis, novelty detection also recruited right ventrolateral PFC and
      bilateral occipito-temporal cortices compared with conceptual recollection,
      suggesting that searching for novel objects heavily relies upon perceptual
      feature processing. Collectively, these data isolate task- from domain-sensitive
      PFC control processes strategically recruited in the service of episodic memory.

PMID- 15728741
TI  - Neural systems underlying observation of humanly impossible movements: an FMRI
      study.
AB  - Previous studies have indicated that largely overlapping parts of a complex,
      mainly fronto-parietal, neural network are activated during both observation and
      execution of an action. If these two processes are inextricably linked, increases
      of neural activity contingent upon action observation should be found only for
      movements that can actually be performed. Using functional magnetic resonance
      imaging, we investigated whether observation of possible and biomechanically
      impossible movements of fingers activated the same neural systems. Thirteen
      healthy subjects were scanned during observation of video-clips showing
      abduction/adduction movements of the right index or the little finger, which were
      defined as biomechanically possible or impossible according to the range of their
      angular displacement at the metacarpo-phalangeal joint. The mere observation of
      possible and impossible hand movements induced a selective activation of left
      precentral and left inferior frontal regions, thus indicating that motor-related
      areas map body actions even when they violate the constraints of human anatomy.
      An increase of the blood oxygen level-dependent signal selectively linked to
      observation of impossible hand movements was found in sensorimotor parietal
      regions. Our results suggest that while premotor areas code human actions
      regardless of whether they are biologically possible or impossible, sensorimotor
      parietal regions may be important for coding the plausibility of actions.

PMID- 15728742
TI  - Selecting among competing alternatives: selection and retrieval in the left
      inferior frontal gyrus.
AB  - It has been widely argued that the left inferior frontal gyrus (LIFG) is involved
      in the control of retrieval of information from long-term memory. Recent claims
      that the LIFG is involved in selecting among semantic alternatives have been
      challenged on the grounds that the manipulation of selection demands may have
      been confounded with controlled retrieval. The current study used an event
      related functional magnetic resonance paradigm to re-examine the possibility that
      LIFG activation is involved in selection processes. In order to minimize
      potential confounding effects of controlled retrieval, we used an automatic
      retrieval task (picture naming) and held retrieval demands constant, while
      varying selection demands by way of competitor priming from earlier semantically
      related trials. We found significant activation in LIFG as a function of
      increased selection demands; activation centred on two peaks, one in anterior
      LIFG and a second more superior and posterior region. These data support the view
      that LIFG plays a role in selection among semantic information, even in the
      absence of controlled retrieval processes.

PMID- 15728745
TI  - The Bangkok Conference: steering countries to build national capacity for health
      promotion.

PMID- 15728744
TI  - Recognition of the spliceosomal branch site RNA helix on the basis of surface and
      electrostatic features.
AB  - We have investigated electrostatic and surface features of an essential region of
      the catalytic core of the spliceosome, the eukaryotic precursor messenger (pre
      m)RNA splicing apparatus. The nucleophile for the first of two splicing reactions
      is the 2'-hydroxyl (OH) of the ribose of a specific adenosine within the intron.
      During assembly of the spliceosome's catalytic core, this adenosine is positioned
      by pairing with a short region of the U2 small nuclear (sn)RNA to form the pre
      mRNA branch site helix. The solution structure of the spliceosomal pre-mRNA
      branch site [Newby,M.I. and Greenbaum,N.L. (2002) Nature Struct. Biol., 9, 958
      965] showed that a phylogenetically conserved pseudouridine (psi) residue in the
      segment of U2 snRNA that pairs with the intron induces a markedly different
      structure compared with that of its unmodified counterpart. In order to achieve a
      more detailed understanding of the factors that contribute to recognition of the
      spliceosome's branch site helix and activation of the nucleophile for the first
      step of pre-mRNA splicing, we have calculated surface areas and electrostatic
      potentials of psi-modified and unmodified branch site duplexes. There was no
      significant difference between the total accessible area or ratio of total
      polar:nonpolar groups between modified and unmodified duplexes. However, there
      was substantially greater exposure of nonpolar area of the adenine base, and less
      exposure of the 2'-OH, in the psi-modified structure. Electrostatic potentials
      computed using a hybrid boundary element and finite difference nonlinear Poisson
      Boltzmann approach [Boschitsch, A.H. and Fenley, M.O. (2004) J. Comput. Chem.,
      25, 935-955] revealed a region of exceptionally negative potential in the major
      groove surrounding the 2'-OH of the branch site adenosine. These surface and
      electrostatic features may contribute to the overall recognition of the pre-mRNA
      branch site region by other components of the splicing reaction.

PMID- 15728743
TI  - Variation in the strength of selected codon usage bias among bacteria.
AB  - Among bacteria, many species have synonymous codon usage patterns that have been
      influenced by natural selection for those codons that are translated more
      accurately and/or efficiently. However, in other species selection appears to
      have been ineffective. Here, we introduce a population genetics-based model for
      quantifying the extent to which selection has been effective. The approach is
      applied to 80 phylogenetically diverse bacterial species for which whole genome
      sequences are available. The strength of selected codon usage bias, S, is found
      to vary substantially among species; in 30% of the genomes examined, there was no
      significant evidence that selection had been effective. Values of S are highly
      positively correlated with both the number of rRNA operons and the number of tRNA
      genes. These results are consistent with the hypothesis that species exposed to
      selection for rapid growth have more rRNA operons, more tRNA genes and more
      strongly selected codon usage bias. For example, Clostridium perfringens, the
      species with the highest value of S, can have a generation time as short as 7
      min.

PMID- 15728747
TI  - Medical comorbidity in geriatric psychiatry.

PMID- 15728748
TI  - Major and subthreshold depression among older adults seeking vision
      rehabilitation services.
AB  - OBJECTIVE: Authors examined the potential risk factors of major and subthreshold
      depression among elderly persons seeking rehabilitation for age-related vision
      impairment. METHODS: Participants (N=584), age 65 and older, with a recent vision
      loss, were new applicants for rehabilitation services. Subthreshold depression
      was defined as a depressive syndrome not meeting criteria for a current major
      depression (i.e., minor depression, major depression in partial remission,
      dysthymia) or significant depressive symptomatology. RESULTS: Seven percent of
      respondents had a current major depression, and 26.9% met the criteria for a
      subthreshold depression. Poorer self-rated health, lower perceived adequacy of
      social support, decreased feelings of self-efficacy, and a past history of
      depression increased the odds of both a subthreshold and major depression, versus
      no depression, but greater functional disability and experiencing a negative life
      event were significant only for a subthreshold depression. Only a history of past
      depression was significant in increasing the odds of having a major versus a
      subthreshold depression. CONCLUSION: Results highlight similarities in
      characteristics of, and risk factors for, subthreshold and major depression.
      Future research is needed to better understand both the trajectory and treatment
      of subthreshold depression, relative to major depressive disorders.

PMID- 15728749
TI  - Body pain and treatment response in late-life depression.
AB  - OBJECTIVE: The authors investigated the influence of body pain on 1) time to
      treatment response and 2) suicidal ideation, in late-life depression. They
      hypothesized that higher levels of body pain would predict a longer time to and
      lower likelihood of response, and increased levels of suicidal ideation. METHODS:
      Subjects (N=187) were older adult outpatients (age > or =69 years), with current
      episodes of major depression, who were openly treated with paroxetine up to 40 mg
      daily and weekly interpersonal psychotherapy. Response was defined as 3
      consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain
      was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment.
      Authors used survival-analysis models on the responder sample to test the effect
      of body pain on response, after controlling for severity of depression. RESULTS:
      Overall response rate was 75.4%. Nonresponders reported more severe pain at
      baseline. After covarying for severity of baseline depression, no effect was
      found for physical pain on time-to-response or degree of suicidality. Bodily pain
      remained stable during acute treatment for responders, independent of depression
      response to combination psychotherapy and antidepressant treatment. CONCLUSIONS:
      Older adult patients with higher levels of physical pain can still respond to
      antidepressant treatment; however, reported bodily pain may be associated with a
      more difficult-to-treat depression.

PMID- 15728750
TI  - Prostate cancer: a significant risk factor for late-life suicide.
AB  - OBJECTIVE: The authors sought to determine the incidence of suicide and its
      relevant correlates among men with prostate cancer. METHODS: This was a
      population-based, retrospective cohort review of men age 65 and older, residing
      in South Florida between 1983 and 1993. Average annual suicide rate was
      calculated for prostate cancer-related suicides and contrasted with age and
      gender-specific rates in the same geographic area. RESULTS: Of 667 completed
      suicides, 20 were prostate cancer-related (3% of the total male suicide sample).
      The average annual incidence of suicide for men was 55.32 per 100,000 persons,
      but for men with prostate cancer, the rate was 274.7 per 100,000. The risk of
      suicide in men with prostate cancer was 4.24 times that of an age- and gender
      specific cohort. The clinical correlates included depression (70%), cancer
      diagnosis within 6 months of suicide (80%), physician visit within 1 month of
      suicide (60%), and being foreign-born (70%). CONCLUSION: The incidence of suicide
      among older men with prostate cancer is higher than previously recognized.
      Depression, recent diagnosis, pain, and being foreign-born are important clinical
      correlates. Screens for depression and suicide in older men with prostate cancer
      should be done after diagnosis and redone during the first 6 months regularly,
      particularly in the primary-care setting. Public education is needed to decrease
      the stigma associated with having a cancer diagnosis.

PMID- 15728751
TI  - How does depression influence diabetes medication adherence in older patients?
AB  - OBJECTIVE: Using various measures (electronic monitoring, patient/provider
      report, pharmacy data), the authors assessed the association between depression
      and diabetes medication adherence among older patients with Type 2 diabetes.
      METHODS: Patients completed a baseline survey on depression (Patient Health
      Questionnaire) and were given electronic monitoring caps (EMCs) to use with their
      oral hypoglycemic medication. At the time of the patient baseline survey,
      providers completed a survey on their patients' overall medication adherence.
      Upon returning the caps after 30 days, patients completed a survey on their
      overall medication adherence. EMC adherence was defined as percent of days out of
      30 with correct number of doses. Using pharmacy refill data from the patient
      baseline through 1 year later, they defined adherence as the percentage of days
      with adequate medication, based on days' supply across refill periods. RESULTS:
      Of 203 patients (mean age: 67 years), 10% (N=19) were depressed. Depressed
      patients were less likely to self-report good adherence and had a lower median
      percentage of days with adequate medication coverage (on the basis of pharmacy
      refill data). After adjustment for alcohol use, cognitive impairment, age, and
      other medication use, depression was still negatively associated with adequate
      adherence, according to patient report and pharmacy data. Depression showed no
      associated with adherence on the basis of provider or EMC data. CONCLUSIONS:
      Depression was independently associated with inadequate medication adherence on
      the basis of patient self-report and pharmacy data.

PMID- 15728752
TI  - A statewide case-control study of spousal homicide-suicide in older persons.
AB  - OBJECTIVE: Homicide-suicides are rare relative to suicides and homicides, but
      these lethal events are an emerging public health concern. They have a mortality
      count similar to meningitis, pulmonary tuberculosis, influenza, and viral
      hepatitis, and the rate may be increasing in the United States, especially among
      older persons. The goal of this case-control study was to identify factors that
      differentiate older married men who commit homicide-suicide from those who commit
      suicide only. METHODS: A total of 20 spousal homicide-suicides involving persons
      age 55 years and older were ascertained in Florida between January 1, 1998 and
      December 31, 1999 from medical examiner records. Two suicide controls were
      matched to each homicide-suicide perpetrator by age, race, marital status, method
      of death, and medical examiner district. Perpetrator groups were compared on
      sociodemographic characteristics, medical variables, and autopsy findings.
      RESULTS: Homicide-suicide perpetrators displayed significantly more domestic
      violence or were caregivers for their wives, in contrast to suicide perpetrators,
      who had health problems and were receiving care from their spouses. Both groups
      of perpetrators had reported depressed mood, and there were no differences in
      sociodemographic factors. CONCLUSIONS: Depression plays a significant role in
      both homicide-suicide and suicide, but the associated factors are different: we
      see caregiving strain in perpetrators of homicide-suicide, and living with
      physical health disorders as a care-recipient in men who commit suicide. Marital
      conflict is a significant factor in some spousal homicide-suicides.

PMID- 15728753
TI  - The Addenbrooke's cognitive examination (ACE) in the differential diagnosis of
      early dementias versus affective disorder.
AB  - OBJECTIVE: The authors describe the profile of performance of patients whose
      cognitive complaint is due to dementia, affective disorder, or combinations
      thereof on the Addenbrooke's Cognitive Examination (ACE) test battery. METHODS:
      Authors tested 90 subjects with dementia (63 Alzheimer disease [AD]; 27 fronto
      temporal dementia [FTD]), 60 subjects with "pure" affective disorder (23 major
      depression [MDD], 37 whose affective symptoms did not meet criteria for major
      depression [Affective]); 22 patients with symptoms of affective disorder and
      organic dementia (Mixed); and 127 healthy volunteers (NC). RESULTS: The total ACE
      scores for the AD, FTD, and Mixed groups were significantly lower than for the NC
      group. Likewise, on total score, the AD and FTD groups scored significantly lower
      than either of the "pure" affective-disorder groups. Within the dementia group,
      the AD group scored significantly lower than the fronto-temporal group.
      CONCLUSIONS: The profile of performance on the ACE of patients with dementia is
      different from that of patients suffering from affective illness. Mild impairment
      in the total ACE score, along with a low score on the memory domain tasks and
      letter fluency (in contrast to normal category fluency), are strongly indicative
      of an affective, as opposed to organic, pathology. A total score of <88 in
      suspected dementia patients with affective symptoms appears strongly predictive
      of an underlying organic disorder.

PMID- 15728754
TI  - Duloxetine for the treatment of major depressive disorder in older patients.
AB  - OBJECTIVE: The efficacy and safety of duloxetine, a dual reuptake inhibitor of
      serotonin (5-HT) and norepinephrine (NE), were evaluated in the treatment of
      major depressive disorder (MDD) and associated pain symptoms in patients age 55
      and older. METHODS: Efficacy data were obtained from patients age > or =55 who
      participated in two identical, multicenter, double-blind studies in which
      patients with MDD were randomized to receive placebo (N=43) or duloxetine (60
      mg/day; N=47) for 9 weeks. The primary efficacy measure was the mean change in
      Ham-D-17 total score. Pain symptoms were assessed with visual-analog scales.
      Safety data for patients age > or =55 were pooled from six randomized, 8- or 9
      week, double-blind studies of duloxetine in which patients with MDD were
      randomized to receive placebo (N=90) or duloxetine (40 mg/day-120 mg/day; N=119).
      RESULTS: The combined results of these two investigations found that duloxetine
      was significantly superior to placebo for mean change in Ham-D-17 total score.
      The estimated probability of remission for duloxetine-treated patients (44.1%)
      was also significantly higher than that for placebo (16.1%). Reductions in
      overall pain, back pain, and pain while awake were also significantly greater for
      duloxetine than placebo. The rate of discontinuation due to adverse events was
      significantly higher for duloxetine-treated patients (21.0%) than placebo (6.7%).
      Abnormal elevations in vital signs at endpoint were not significantly different
      from placebo. CONCLUSIONS: In these two investigations, duloxetine 60 mg/day was
      an efficacious treatment for MDD and also alleviated pain symptoms in depression
      patients age 55 and older.

PMID- 15728755
TI  - Assessing mental health and its association with income and resource utilization
      in old-old Chinese in Hong Kong.
AB  - OBJECTIVES: The authors assessed mental health status and its association with
      income and resource utilization in old-old Chinese citizens in Hong Kong.
      METHODS: Stratified disproportional random sampling in 1991-92 assembled a cohort
      of 1,696 elderly community-dwelling subjects who were age 70 or above, measuring
      the age and education adjusted mean level of cognitive functioning and geriatric
      depression, by income groups and further investigating the association between
      mental health and income by incorporating deficiencies in activities of daily
      living (ADL) and the presence of major chronic conditions in the multivariate
      regressions. The association between mental health and resource utilization,
      including physician visits and use of medication, was examined by multivariate
      regression analyses. RESULTS: Better cognitive functioning was associated with
      higher income across groups. Lower geriatric depression was associated with
      higher income. Cognitive impairment was associated with the ADL deficiencies, and
      geriatric depression was associated with a number of major chronic conditions and
      higher resource utilization, including physician visits and medication use.
      CONCLUSIONS: Income was significantly associated with cognitive functioning and
      geriatric depression in elderly persons in Hong Kong. Mental health, ADL
      deficiency, major chronic conditions, and resource utilization are interrelated.
      The fact that aging in the population is associated with increasing cognitive
      impairment and geriatric depression presents new challenges in financing and
      delivering efficient and equitable health care in the region.

PMID- 15728756
TI  - IADL functions, cognitive deficits, and severity of depression: a preliminary
      study.
AB  - OBJECTIVE: Despite the documented association of cognitive dysfunction with
      impairment in instrumental activities of daily living (IADLs) in geriatric
      depression, the relationship among deficits in distinct IADLs with severity of
      depression and specific cognitive impairments remains to be clarified. The
      authors examined the relationship of depression severity and the cognitive
      domains of attention, initiation/perseveration, construction, conceptualization,
      and memory to nine distinct IADLs. METHODS: The subjects were 105 nondemented
      elderly patients but with impairment in at least one IADL and a history or
      presence of major depression. Impairment in IADLs and severity of depression were
      assessed with the Philadelphia Multilevel Assessment Instrument (MAI) and the 24
      item Hamilton Depression Rating Scale (Ham-D), respectively. Cognitive
      dysfunction was assessed with the Mini-Mental State Exam (MMSE) and the Mattis
      Dementia Rating Scale (DRS). RESULTS: Six IADLs were influenced by impairment in
      at least one of the cognitive domains. Abnormal scores in
      initiation/perseveration, an aspect of executive dysfunction, was the cognitive
      impairment affecting most IADLs; it interfered with the ability to shop for
      groceries, prepare meals, take medicine, and manage money. Impairment in
      initiation/perseveration had a most prominent effect in the presence of
      depressive symptoms and affected shopping for groceries and preparing meals. Lack
      of interest and motivation, part of the depressive syndrome, compounded by
      behavioral abnormalities resulting from executive dysfunction, may account for
      this interaction. CONCLUSIONS: These relationships may provide the background for
      developing interventions targeting functional deficits associated with specific
      cognitive dysfunctions and depression.

PMID- 15728757
TI  - General-medical conditions in older patients with serious mental illness.
AB  - OBJECTIVE: The burden of medical comorbidities was compared between older (> or
      =60 years) and younger patients with serious mental illness. METHODS: Patients
      (N=8,083) diagnosed with schizophrenia, schizoaffective disorder, or bipolar
      disorder in 2001 were identified from VA facilities in the mid-Atlantic region.
      Medical comorbidities were identified by an ICD-9-based clinical classification
      algorithm. RESULTS: Older, versus younger, patients were more likely to be
      diagnosed with cardiovascular or pulmonary conditions, and less likely to be
      diagnosed with substance-use disorders or hepatic conditions. CONCLUSIONS: More
      aggressive detection and management of general-medical comorbidities in older
      patients with serious mental illness is paramount.

PMID- 15728758
TI  - Stability of visual acuity measurement in depression.
AB  - OBJECTIVE: The authors sought to determine whether depression influences the
      measurement of visual acuity (VA) in older persons. METHODS: This was a
      prospective study, in a geriatric psychiatry inpatient unit. Participants were 32
      older patients with major depression. Authors measured VA before and after
      treatment of major depression, as measured by the Center for Epidemiologic
      Studies Depression Scale (CES-D). RESULTS: As depression resolved, there was no
      significant change in VA from admission to discharge. CES-D scores significantly
      declined from admission to discharge. VA was not correlated with depression
      severity (CES-D score) either at baseline or at discharge. CONCLUSION: This study
      found no evidence that depression influenced VA testing in older adults.
      Additional studies in patients with major eye diseases are necessary to evaluate
      the generalizability of this finding.

PMID- 15728759
TI  - Prehension synergies: trial-to-trial variability and principle of superposition
      during static prehension in three dimensions.
AB  - We performed three-dimensional analysis of the conjoint changes of digit forces
      during prehension (prehension synergies) and tested applicability of the
      principle of superposition to three-dimensional tasks. Subjects performed 25
      trials at statically holding a handle instrumented with six-component
      force/moment sensors under seven external torque conditions; -0.70, -0.47, -0.23,
      0.00, 0.23, 0.47, and 0.70 Nm about a horizontal axis in the plane passing
      through the centers of all five digit force sensors (the grasp plane). The total
      weight of the system was always 10.24 N. The trial-to-trial variability of the
      forces produced by the thumb and the virtual finger (an imagined finger producing
      the same mechanical effects as all 4 finger forces and moments combined)
      increased in all three dimensions with the external torque magnitude. The sets of
      force and moment variables associated with the moment production about the
      vertical axis in the grasp plane and the axis orthogonal to the grasp plane
      consisted of two noncorrelated subsets each; one subset of variables was related
      to the control of grasping forces (grasp control) and the other sassociated with
      the control of the orientation of the hand-held object (torque control). The
      variables associated with the moment production about the horizontal axis in the
      grasp plane did not include the grip force (the normal thumb and virtual finger
      forces) and showed more complex noncorrelated subsets. We conclude that the
      principle of superposition is valid for the prehension in three dimensions. The
      observed high correlations among forces and moments associated with the control
      of object orientation could be explained by chain effects, the sequences of cause
      effect relations necessitated by mechanical constraints.

PMID- 15728760
TI  - Effects of GABA receptor antagonists on retinal glycine receptors and on
      homomeric glycine receptor alpha subunits.
AB  - Glycinergic and GABAergic inhibition are juxtaposed at one retinal synaptic layer
      yet likely perform different functions. These functions have usually been
      evaluated using receptor antagonists. In examining retinal glycine receptors, we
      were surprised to find that commonly used concentrations of GABA antagonists
      blocked significant fractions of the glycine current. In retinal amacrine and
      ganglion cells, the competitive GABAA receptor antagonists (bicuculline and
      SR95531) were also competitive GlyR antagonists. Picrotoxinin produced a
      noncompetitive inhibition of retinal GlyRs. [1,2,5,6-tetrahydropyridine-4-yl]
      methylphosphinic acid, the GABACR antagonist, did not inhibit glycine receptors.
      All three GABAA receptor antagonists were competitive inhibitors of homomeric
      alpha1 or alpha2 GlyRs expressed in human embryonic kidney cells (HEK293) cells.
      Interestingly, bicuculline was much more effective at alpha2 GlyRs and might be
      used to separate glycine receptor subtypes. Thus commonly used concentrations of
      GABA antagonists do not unambiguously differentiate GABA and glycine pathways.
      Picrotoxinin inhibition of GABAC receptors requires two amino acids in the second
      transmembrane region (TM2): 2' serine and 6' threonine. Although TM2 regions in
      GABA and glycine receptors are highly homologous, neither 2' serine nor 6'
      threonine is essential for picrotoxinin sensitivity in glycine receptors.

PMID- 15728761
TI  - Distinct roles for lateral and medial anterior prefrontal cortex in contextual
      recollection.
AB  - A key feature of human recollection is the ability to remember details of the
      context in which events were experienced, as well as details of the events
      themselves. Previous studies have implicated a number of regions of prefrontal
      cortex in contextual recollection, but the role of anterior prefrontal cortex has
      so far resisted detailed characterization. We used event-related functional MRI
      (fMRI) to contrast recollection of two forms of contextual information: 1)
      decisions one had previously made about stimuli (task memory) and 2) which of two
      temporally distinct lists those stimuli had been presented in (list memory). In
      addition, a retrieval cue manipulation permitted evaluation of the stage of the
      retrieval process in which the activated regions might be involved. The results
      indicated that anterior prefrontal cortex responded significantly more during
      recollection of task than list context details. Furthermore, activation profiles
      for lateral and medial aspects of anterior prefrontal cortex suggested differing
      roles in recollection. Lateral regions seem to be more involved in the early
      retrieval specification stages of recollection, with medial regions contributing
      to later stages (e.g., monitoring and verification).

PMID- 15728762
TI  - Countermanding eye-head gaze shifts in humans: marching orders are delivered to
      the head first.
AB  - The countermanding task requires subjects to cancel a planned movement on
      appearance of a stop signal, providing insights into response generation and
      suppression. Here, we studied human eye-head gaze shifts in a countermanding task
      with targets located beyond the horizontal oculomotor range. Consistent with head
      restrained saccadic countermanding studies, the proportion of gaze shifts on stop
      trials increased the longer the stop signal was delayed after target
      presentation, and gaze shift stop-signal reaction times (SSRTs: a derived
      statistic measuring how long it takes to cancel a movement) averaged
      approximately 120 ms across seven subjects. We also observed a marked proportion
      of trials (13% of all stop trials) during which gaze remained stable but the head
      moved toward the target. Such head movements were more common at intermediate
      stop signal delays. We never observed the converse sequence wherein gaze moved
      while the head remained stable. SSRTs for head movements averaged approximately
      190 ms or approximately 70-75 ms longer than gaze SSRTs. Although our findings
      are inconsistent with a single race to threshold as proposed for controlling
      saccadic eye movements, movement parameters on stop trials attested to
      interactions consistent with a race model architecture. To explain our data, we
      tested two extensions to the saccadic race model. The first assumed that gaze
      shifts and head movements are controlled by parallel but independent races. The
      second model assumed that gaze shifts and head movements are controlled by a
      single race, preceded by terminal ballistic intervals not under inhibitory
      control, and that the head-movement branch is activated at a lower threshold.
      Although simulations of both models produced acceptable fits to the empirical
      data, we favor the second alternative as it is more parsimonious with recent
      findings in the oculomotor system. Using the second model, estimates for gaze and
      head ballistic intervals were approximately 25 and 90 ms, respectively,
      consistent with the known physiology of the final motor paths. Further, the
      threshold of the head movement branch was estimated to be 85% of that required to
      activate gaze shifts. From these results, we conclude that a commitment to a head
      movement is made in advance of gaze shifts and that the comparative SSRT
      differences result primarily from biomechanical differences inherent to eye and
      head motion.

PMID- 15728763
TI  - Effect of stimulus size on the dynamics of orientation selectivity in Macaque V1.
AB  - Previous research has established that orientation selectivity depends to a great
      extent on suppressive mechanisms in the visual cortex. In this study, we
      investigated the spatial organization and the time-course of these mechanisms.
      Stimuli were presented in circular windows of "optimal" and "large" radii. The
      two stimulus sizes were chosen based on an area-response function measured with
      drifting gratings at high contrast. The "optimal" size was defined as the
      smallest radius that elicited the peak response (average value of 0.45 degrees ),
      whereas "large" was defined as two to five times the optimal size. We found that
      the peak amplitude of tuned enhancement and untuned suppression varied <10% on
      average with stimulus radius, indicating that they are mainly concentrated in the
      classical receptive field. However, tuned suppression--in those cells that showed
      it--was significantly stronger with large stimuli, indicating that this component
      has a contribution from beyond the classical receptive field. These results imply
      that spatial context (in large stimuli) enhances orientation selectivity by
      increasing tuned suppression. We also characterized the time evolution of
      enhancement, of untuned suppression, and of tuned suppression. The time-course of
      tuned suppression was markedly slower in time-to-peak and longer in its
      persistence than untuned suppression. Therefore tuned suppression is likely to be
      generated by long-range recurrent connections or cortico-cortical feedback,
      whereas untuned suppression is mainly generated locally in V1.

PMID- 15728764
TI  - Activation of nucleus basalis facilitates cortical control of a brain stem motor
      program.
AB  - We tested the hypothesis that activation of nucleus basalis magnocellularis
      (NBM), which provides cholinergic input to cortex, facilitates motor control. Our
      measures of facilitation were changes in the direction and time-course of
      vibrissa movements that are elicited by microstimulation of vibrissa motor (M1)
      cortex. In particular, microstimulation led solely to a transient retraction of
      the vibrissae in the sessile animal but to a full motion sequence of protraction
      followed by retraction in the aroused animal. We observed that activation of NBM,
      as assayed by cortical desynchronization, induced a transition from
      microstimulation-evoked retraction to full sweep sequences. This dramatic change
      in the vibrissa response to microstimulation was blocked by systemic delivery of
      atropine and, in anesthetized animals, an analogous change was blocked by the
      topical administration of atropine to M1 cortex. We conclude that NBM
      significantly facilitates the ability of M1 cortex to control movements. Our
      results bear on the importance of cholinergic activation in schemes for
      neuroprosthetic control of movement.

PMID- 15728765
TI  - Contrast and temporal frequency-related adaptation in the pretectal nucleus of
      the optic tract.
AB  - In mammals, many cells in the retino-geniculate-cortical pathway adapt during
      stimulation with high contrast gratings. In the visual cortex, adaptation to high
      contrast images reduces sensitivity at low contrasts while only moderately
      affecting sensitivity at high contrasts, thus generating rightward shifts in the
      contrast response functions (contrast gain control). Similarly, motion adaptation
      at particular temporal frequencies (TFs) alters the temporal tuning properties of
      cortical cells. For the first time in any species, this paper investigates the
      influence of motion adaptation on both the contrast and TF responses of neurons
      in the retino-pretectal pathway by recording from direction-selective neurons in
      the nucleus of the optic tract (NOT) of the marsupial wallaby, Macropus eugenii.
      This species is of interest because its NOT receives almost all input directly
      from the retina, with virtually none from the visual cortex (unlike cats and
      primates). All NOT cells show changes in their contrast response functions after
      adaptation, many revealing contrast gain control. Contrast adaptation is
      direction-dependent, preferred directions producing the largest changes. The lack
      of cortical input suggests that contrast adaptation is generated independently
      from the cortex in the NOT or retina. Motion adaptation also produces direction
      selective effects on the TF tuning of NOT neurons by shifting the location of the
      optimum TF. Cells that show strong adaptation to contrast also tend to show large
      changes in TF tuning, suggesting similar intracellular mechanisms. The data are
      discussed in terms of the generality of contrast adaptation across mammalian
      species and across unconnected brain regions within the same species.

PMID- 15728766
TI  - Furosemide and mannitol suppression of epileptic activity in the human brain.
AB  - Most research on basic mechanisms of epilepsy and the design of new antiepileptic
      drugs has focused on synaptic transmission or action potential generation.
      However, a number of laboratory studies have suggested that nonsynaptic
      mechanisms, such as modulation of electric field interactions via the
      extracellular space (ECS), might also contribute to neuronal hypersynchrony and
      epileptogenicity. To date, a role for nonsynaptic modulation of epileptic
      activity in the human brain has not been investigated. Here we studied the
      effects of molecules that modulate the volume and water content of the ECS on
      epileptic activity in patients suffering from neocortical and mesial temporal
      lobe epilepsy. Electrophysiological and optical imaging data were acquired from
      the exposed cortices of anesthetized patients undergoing surgical treatment for
      intractable epilepsy. Patients were given a single intravenous injection
      containing either 20 mg furosemide (a cation-chloride cotransporter antagonist)
      or 50 g mannitol (an osmolyte). Furosemide and mannitol both significantly
      suppressed spontaneous epileptic spikes and electrical stimulation-evoked
      epileptiform discharges in all subjects, completely blocking all epileptic
      activity in some patients without suppressing normal electroencephalographic
      activity. Optical imaging suggested that the spread of electrical stimulation
      evoked activity over the cortex was significantly reduced by these treatments,
      but the magnitude of neuronal activation near the stimulating electrode was not
      diminished. These results suggest that nonsynaptic mechanisms play a critical
      role in modulating the epileptogenicity of the human brain. Furosemide and other
      drugs that modulate the ECS might possess clinically useful antiepileptic
      properties, while avoiding the side effects associated with the suppression of
      neuronal excitability.

PMID- 15728767
TI  - Vestibular perception and action employ qualitatively different mechanisms. I.
      Frequency response of VOR and perceptual responses during Translation and Tilt.
AB  - To investigate the neural mechanisms that humans use to process the ambiguous
      force measured by the otolith organs, we measured vestibuloocular reflexes (VORs)
      and perceptions of tilt and translation. One primary goal was to determine if the
      same, or different, mechanisms contribute to vestibular perception and action. We
      used motion paradigms that provided identical sinusoidal inter-aural otolith cues
      across a broad frequency range. We accomplished this by sinusoidally tilting (20
      degrees, 0.005-0.7 Hz) subjects in roll about an earth-horizontal, head-centered,
      rotation axis ("Tilt") or sinusoidally accelerating (3.3 m/s2, 0.005-0.7 Hz)
      subjects along their inter-aural axis ("Translation"). While identical inter
      aural otolith cues were provided by these motion paradigms, the canal cues were
      substantially different because roll rotations were present during Tilt but not
      during Translation. We found that perception was dependent on canal cues because
      the reported perceptions of both roll tilt and inter-aural translation were
      substantially different during Translation and Tilt. These findings match
      internal model predictions that rotational cues from the canals influence the
      neural processing of otolith cues. We also found horizontal translational VORs at
      frequencies >0.2 Hz during both Translation and Tilt. These responses were
      dependent on otolith cues and match simple filtering predictions that
      translational VORs include contributions via simple high-pass filtering of
      otolith cues. More generally, these findings demonstrate that internal models
      govern human vestibular "perception" across a broad range of frequencies and that
      simple high-pass filters contribute to human horizontal translational VORs
      ("action") at frequencies above approximately 0.2 Hz.

PMID- 15728768
TI  - Encoding and retrieval in the CA3 region of the hippocampus: a model of theta
      phase separation.
AB  - Past research conducted by Hasselmo et al. in 2002 suggests that some fundamental
      tasks are better accomplished if memories are encoded and recovered during
      different parts of the theta cycle. A model of the CA3 subfield of the
      hippocampus is presented, using biophysical representations of the major cell
      types including pyramidal cells and two types of interneurons. Inputs to the
      network come from the septum and the entorhinal cortex (directly and by the
      dentate gyrus). A mechanism for parsing the theta rhythm into two epochs is
      proposed and simulated: in the first half, the strong, proximal input from the
      dentate to a subset of CA3 pyramidal cells and coincident, direct input from the
      entorhinal cortex to other pyramidal cells creates an environment for
      strengthening synapses between cells, thus encoding information. During the
      second half of theta, cueing signals from the entorhinal cortex, by the dentate,
      activate previously strengthened synapses, retrieving memories. Slow inhibitory
      neurons (O-LM cells) play a role in the disambiguation during retrieval. We
      compare and contrast our computational results with existing experimental data
      and other contemporary models.

PMID- 15728769
TI  - Depressed responses of facilitatory synapses.
AB  - We show that when temporal summation takes place, depression of postsynaptic
      responses may ensue when the underlying synaptic conductance change is constant
      or even facilitatory. We term this phenomenon "apparent depression." Such
      apparent depression is most notable for slow synaptic conductance changes, for
      high frequency, and when the synapse is located at distal dendritic sites. We
      show that, when temporal summation ensues, the erroneous estimation of short-term
      synaptic plasticity arises partially from the conventional measurement of
      synaptic dynamics at postsynaptic potential peak time. This can be corrected when
      measuring overlapping synaptic responses at fixed intervals after stimulus time.
      Somatic voltage clamp also helps to partially correct for the apparent
      depression, but a good model of the neuron can do even better in providing a more
      accurate view of the underlying synaptic conductances.

PMID- 15728770
TI  - Neural processes associated with antisaccade task performance investigated with
      event-related FMRI.
AB  - One of the hallmarks of cognitive control is the suppression of prepotent but
      inappropriate responses. Here we used event-related functional MRI to measure
      functional brain activation during a stimulus-response incompatibility task.
      Subjects were instructed before a stimulus appeared either to look at the
      stimulus (prosaccade) or to look away from the stimulus (antisaccade). Eye
      movements were recorded so that functional brain activation could be grouped into
      prosaccades, correct antisaccades, and errors (saccades toward the stimulus on
      antisaccade trials). Correct antisaccade trials were associated with
      significantly more activation in frontal and parietal cortical areas compared
      with prosaccade trials during the late preparatory period before stimulus
      appearance. Correct antisaccades evoked more activation than errors in the right
      dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and
      presupplementary eye fields during this period. No significant differences were
      found for any comparisons early in the preparatory period. Our data suggest that
      the preparation of an antisaccade activates a large frontal and parietal network
      that may be involved in presetting the oculomotor system for the antisaccade
      task. These findings indicate that a large network of frontal and posterior areas
      is modulated during the latter component of the preparatory period on antisaccade
      compared with prosaccade trials. The results further suggest that the activation
      level of frontal cortical areas before stimulus presentation is associated with
      subjects' performance in the antisaccade task. In contrast, we found no areas
      that were more active for correct antisaccades than prosaccades or for correct
      antisaccades than error antisaccades during the stimulus-response period. In
      fact, a number of posterior cortical areas and a few areas in the superior
      frontal lobe were more active during the stimulus-response period on prosaccade
      trials than on antisaccade trials. Error antisaccades showed a larger activation
      in the ACC during the stimulus-response period compared with correct
      antisaccades.

PMID- 15728772
TI  - Kinematics in newly walking toddlers does not depend upon postural stability.
AB  - When a toddler starts to walk without support, gait kinematics and
      electromyographic (EMG) activity differ from those of older children and the body
      displays considerable oscillations due to poor equilibrium. Postural instability
      clearly affects motor patterns in adults, but does instability explain why
      toddlers walk with a different gait? Here we addressed this question by comparing
      kinematics and EMGs in toddlers performing their first independent steps with or
      without hand or trunk support. Hand support significantly improved postural
      stability and some general gait parameters, reducing percent of falls, step
      width, lateral hip deviations and trunk oscillations. However, the kinematic and
      EMG patterns were unaffected by increased postural stability. In particular, the
      co-variance of the angular motion of the lower limb segments, the pattern of
      bilateral coordination of the vertical movement of the two hip joints, high
      variability of the foot path, the elliptic or single peak trajectory of the foot
      in the swing phase, and characteristic EMG bursts at foot contact remained
      idiosyncratic of toddler locomotion. Instead the toddler pattern shared
      fundamental features with adult stepping in place, suggesting that toddlers
      implement a mixed locomotor strategy, combining forward progression with elements
      of stepping in place. Furthermore, gait kinematics remained basically unchanged
      until the occurrence of the first unsupported steps and rapidly matured
      thereafter. We conclude that idiosyncratic features in newly walking toddlers do
      not simply result from undeveloped balance control but may represent an innate
      kinematic template of stepping.

PMID- 15728771
TI  - Direct evidence for a position input to the smooth pursuit system.
AB  - When objects move in our environment, the orientation of the visual axis in space
      requires the coordination of two types of eye movements: saccades and smooth
      pursuit. The principal input to the saccadic system is position error, whereas it
      is velocity error for the smooth pursuit system. Recently, it has been shown that
      catch-up saccades to moving targets are triggered and programmed by using
      velocity error in addition to position error. Here, we show that, when a visual
      target is flashed during ongoing smooth pursuit, it evokes a smooth eye movement
      toward the flash. The velocity of this evoked smooth movement is proportional to
      the position error of the flash; it is neither influenced by the velocity of the
      ongoing smooth pursuit eye movement nor by the occurrence of a saccade, but the
      effect is absent if the flash is ignored by the subject. Furthermore, the
      response started around 85 ms after the flash presentation and decayed with an
      average time constant of 276 ms. Thus this is the first direct evidence of a
      position input to the smooth pursuit system. This study shows further evidence
      for a coupling between saccadic and smooth pursuit systems. It also suggests that
      there is an interaction between position and velocity error signals in the
      control of more complex movements.

PMID- 15728773
TI  - Transient depression of excitatory synapses on interneurons contributes to
      epileptiform bursts during gamma oscillations in the mouse hippocampal slice.
AB  - Persistent gamma frequency (30-70 Hz) network oscillations occur in hippocampal
      slices under conditions of metabotropic glutamate receptor (mGluR) activation.
      Excessive mGluR activation generated a bistable pattern of network activity
      during which epochs of gamma oscillations of increasing amplitude were terminated
      by synchronized bursts and very fast oscillations (>70 Hz). We provide
      experimental evidence that, during this behavior, pyramidal cell-to-interneuron
      synaptic depression takes place, occurring spontaneously during the gamma rhythm
      and associated with the onset of epileptiform bursts. We further provide evidence
      that excitatory postsynaptic potentials (EPSPs) in pyramidal cells are
      potentiated during the interburst gamma oscillation. When these two types of
      synaptic plasticity are incorporated, phenomenologically, into a network model
      previously shown to account for many features of persistent gamma oscillations,
      we find that epochs of gamma do indeed alternate with epochs of very fast
      oscillations and epileptiform bursts. Thus the same neuronal network can generate
      either gamma oscillations or epileptiform bursts, in a manner depending on the
      degree of network drive and network-induced fluctuations in synaptic efficacies.

PMID- 15728774
TI  - Effect of electrical coupling on ionic current and synaptic potential
      measurements.
AB  - Recent studies have found electrical coupling to be more ubiquitous than
      previously thought, and coupling through gap junctions is known to play a crucial
      role in neuronal function and network output. In particular, current spread
      through gap junctions may affect the activation of voltage-dependent conductances
      as well as chemical synaptic release. Using voltage-clamp recordings of two
      strongly electrically coupled neurons of the lobster stomatogastric ganglion and
      conductance-based models of these neurons, we identified effects of electrical
      coupling on the measurement of leak and voltage-gated outward currents, as well
      as synaptic potentials. Experimental measurements showed that both leak and
      voltage-gated outward currents are recruited by gap junctions from neurons
      coupled to the clamped cell. Nevertheless, in spite of the strong coupling
      between these neurons, the errors made in estimating voltage-gated conductance
      parameters were relatively minor (<10%). Thus in many cases isolation of coupled
      neurons may not be required if a small degree of measurement error of the voltage
      gated currents or the synaptic potentials is acceptable. Modeling results show,
      however, that such errors may be as high as 20% if the gap-junction position is
      near the recording site or as high as 90% when measuring smaller voltage-gated
      ionic currents. Paradoxically, improved space clamp increases the errors arising
      from electrical coupling because voltage control across gap junctions is poor for
      even the highest realistic coupling conductances. Furthermore, the common
      procedure of leak subtraction can add an extra error to the conductance
      measurement, the sign of which depends on the maximal conductance.

PMID- 15728776
TI  - V2 receptor antagonists in cystic kidney diseases: an exciting step towards a
      practical treatment.

PMID- 15728775
TI  - Computational model of electrically coupled, intrinsically distinct pacemaker
      neurons.
AB  - Electrical coupling between neurons with similar properties is often studied.
      Nonetheless, the role of electrical coupling between neurons with widely
      different intrinsic properties also occurs, but is less well understood. Inspired
      by the pacemaker group of the crustacean pyloric network, we developed a
      multicompartment, conductance-based model of a small network of intrinsically
      distinct, electrically coupled neurons. In the pyloric network, a small
      intrinsically bursting neuron, through gap junctions, drives 2 larger, tonically
      spiking neurons to reliably burst in-phase with it. Each model neuron has 2
      compartments, one responsible for spike generation and the other for producing a
      slow, large-amplitude oscillation. We illustrate how these compartments interact
      and determine the dynamics of the model neurons. Our model captures the dynamic
      oscillation range measured from the isolated and coupled biological neurons. At
      the network level, we explore the range of coupling strengths for which
      synchronous bursting oscillations are possible. The spatial segregation of ionic
      currents significantly enhances the ability of the 2 neurons to burst
      synchronously, and the oscillation range of the model pacemaker network depends
      not only on the strength of the electrical synapse but also on the identity of
      the neuron receiving inputs. We also compare the activity of the electrically
      coupled, distinct neurons with that of a network of coupled identical bursting
      neurons. For small to moderate coupling strengths, the network of identical
      elements, when receiving asymmetrical inputs, can have a smaller dynamic range of
      oscillation than that of its constituent neurons in isolation.

PMID- 15728777
TI  - Building the glomerulus: a matricentric view.

PMID- 15728778
TI  - Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on
      polycystic kidney disease development in the PCK rat.
AB  - cAMP plays a major role in cystogenesis. Recent in vitro studies suggested that
      cAMP stimulates B-Raf/ERK activation and proliferation of cyst-derived cells in a
      Ca(2+) inhibitable, Ras-dependent manner. OPC-31260, a vasopressin V2 receptor
      (VPV2) antagonist, was shown to lower renal cAMP and inhibit renal disease
      development and progression in models orthologous to human cystic diseases. Here
      it is shown that OPC-41061, an antagonist chosen for its potency and selectivity
      for human VPV2, is effective in PCK rats. PCK kidneys have increased Ras-GTP and
      phosphorylated ERK levels and 95-kD/68-kD B-Raf ratios, changes that are
      corrected by the administration of OPC-31260 or OPC-41061. These results support
      the importance of cAMP in the pathogenesis of polycystic kidney disease, confirm
      the effectiveness of a VPV2 antagonist to be used in clinical trials for this
      disease, and suggest that OPC-31260 and OPC-41061 inhibit Ras/mitogen-activated
      protein kinase signaling in polycystic kidneys.

PMID- 15728779
TI  - Kinesin family member 12 is a candidate polycystic kidney disease modifier in the
      cpk mouse.
AB  - The cpk mouse is the most extensively characterized model of autosomal recessive
      polycystic kidney disease (ARPKD). The major ARPKD-related renal and biliary
      phenotypes are modulated in F2 mutants by genetic background, suggesting that
      quantitative trait loci (QTL) modulate disease severity. In 461 F2 cpk mice,
      kidney length, weight, and volume were scored as quantitative traits (QT), and a
      semiquantitative method to assess biliary duct number, area (BDA), portal vein
      area, and total area of each portal field, as well as the severity of
      cholangitis, was developed. QTL mapping was performed with Pseudomarker v1.02.
      Candidate genes were identified within the QTL intervals on the basis of
      expression profiling, reverse transcriptase-PCR, haplotypes, and sequence
      analysis. The renal QT were normally distributed in the F2 cohort and strongly
      correlated (P < 0.001). Among the biliary QT, only BDA correlated with the renal
      QT (P < 0.01). Genome-wide scan identified a major effect QTL on chromosome (Chr)
      4 for the renal traits, adjusted BDA, and cholangitis with logarithm of odds
      scores of 18, 8, and 5, respectively. Regression modeling refined the Chr 4 main
      effect into an approximately 50-cM region with three distinct QTL peaks at 16,
      34, and 54 cM. Kif12, a gene encoding a novel kinesin, mapped beneath the 34 cM
      QTL peak and has expression level variants and strain-specific sequences that
      were associated with renal disease severity in affected mice. Therefore, the
      positional candidate gene, Kif12, fulfills the major criteria for QTL gene
      discovery established by the Complex Trait Consortium, and, thus, it is proposed
      that Kif12 is a cpk modifier gene.

PMID- 15728780
TI  - Thrombophilia and the risk for hemodialysis vascular access thrombosis.
AB  - Vascular access thrombosis is the most common and costly complication in
      hemodialysis patients. The role of thrombophilia in access thrombosis is not
      established. A case-control study was conducted of 419 hemodialysis patients to
      determine whether thrombophilia was associated with arteriovenous fistula or
      graft thrombosis. Participants were enrolled from three in-center and five
      satellite dialysis units associated with a Canadian academic health science
      center that provides dialysis services in a catchment area of one million.
      Patients were tested for factor V Leiden, prothrombin gene mutation, factor XIII
      genotype, methylenetetrahydrofolate reductase genotype, lupus anticoagulant,
      anticardiolipin antibody, factor VIII, homocysteine, and lipoprotein (a)
      concentrations. Overall, 59 (55%) patients with access thrombosis had at least
      one thrombophilia compared with 122 (39%) patients without access thrombosis
      (unadjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.23 to 2.98).
      After controlling for important risk factors, the association between any
      thrombophilia and access thrombosis remained (adjusted OR, 2.42; 95% CI, 1.47 to
      3.99). For each additional thrombophilic disorder, the odds of access thrombosis
      increased significantly (adjusted OR, 1.87; 95% CI, 1.34 to 2.61). This study
      suggests that thrombophilia is associated with access thrombosis in dialysis
      patients. Large, multicenter, prospective cohort studies are needed to confirm
      the observations from this case-control study.

PMID- 15728781
TI  - Hemolytic uremic syndrome.

PMID- 15728782
TI  - Protective effect of carbon monoxide-releasing compounds in ischemia-induced
      acute renal failure.
AB  - Heme oxygenase (HO) induction has been demonstrated to be beneficial in limiting
      the extent of cellular damage after ischemia-induced acute renal failure (ARF).
      Because increased HO activity is associated with the production of carbon
      monoxide (CO) as well as the potent antioxidant bilirubin, it is unclear which of
      the two is of greater importance in the protective effects of HO induction. The
      purpose of this study was to determine the protective role of CO alone in
      ischemia-induced ARF. Bilateral clamping of the renal pedicle for 40 min was
      associated with a ninefold increase in the levels of plasma creatinine 24 h after
      reperfusion as compared with normal plasma creatinine levels; however,
      administration of CO donor compounds tricarbonyldichlororuthenium(II) dimer,
      ([Ru(CO)(3)Cl(2)](2), 10 mg/kg) or tricarbonylchloro(glycinato)ruthenium(II)
      ([Ru(CO)(3)Cl(glycinate)], (CORM-3) 1 h before the onset of ischemia
      significantly decreased the levels of plasma creatinine 24 h after reperfusion as
      compared with vehicle-treated mice. Surprising, treatment with the CO donors was
      associated with an increase in HO activity 24 h after ischemia. For determining
      whether the protective effects of the CO donors were due to CO or HO-1 induction,
      experiments were performed in which HO was inhibited before administration of the
      CO donors. Pretreatment with the HO inhibitor had no effect on the level of
      plasma creatinine 24 h after reperfusion after treatment with the CO donor
      compounds. These results suggest that CO itself may be protective and limit renal
      damage in ischemia induced ARF.

PMID- 15728783
TI  - Erythropoietin increases asymmetric dimethylarginine in endothelial cells: role
      of dimethylarginine dimethylaminohydrolase.
AB  - Recombinant human erythropoietin therapy frequently causes hypertension in humans
      and animals with chronic renal failure. Asymmetric dimethylarginine (ADMA) is an
      endogenous inhibitor of nitric oxide (NO) synthase, and its accumulation has been
      associated with reducing NO bioavailability and increasing superoxide generation.
      Whether epoetin beta (EPO) or darbepoetin alpha (NESP) can modify the levels of
      ADMA in endothelial cells was investigated. Endothelial cells from the third
      passage were incubated for 24 h in the presence of various concentrations of EPO
      or NESP (0, 0.1, 1, 10, 50, 100, and 200 U/ml). The levels of ADMA, allantoin,
      nitrate, and nitrite in conditioned media and the activity of dimethylarginine
      dimethylaminohydrolase (DDAH), the content of thiols and reactive oxygen species
      in endothelial cells, were determined. When endothelial cells were exposed to EPO
      or NESP, ADMA concentration in the cell culture medium increased significantly in
      a dose-dependent manner versus control. This effect was associated with a reduced
      activity of DDAH, the enzyme that degrades ADMA. Furthermore, EPO- or NESP
      induced accumulation of ADMA was accompanied by a significant reduction of NO
      synthesis and an increase in oxidative stress. Both allantoin, a marker of oxygen
      free radical generation, and reactive oxygen species increased significantly
      after EPO or NESP treatment compared with control. The antioxidant pyrrolidine
      dithiocarbamate preserved DDAH activity and reduced ADMA accumulation in the same
      way as the co-incubation with anti-EPO neutralizing antibody. EPO and NESP
      posttranslationally impair DDAH activity via increased oxidative stress, causing
      ADMA as an important cardiovascular risk factor to accumulate and inhibit NO
      synthesis.

PMID- 15728784
TI  - Long-term study of mycophenolate mofetil as continuous induction and maintenance
      treatment for diffuse proliferative lupus nephritis.
AB  - Mycophenolate mofetil (MMF) and the sequential use of cyclophosphamide followed
      by azathioprine (CTX-AZA) demonstrate similar short-term efficacy in the
      treatment of diffuse proliferative lupus nephritis (DPLN), but MMF is associated
      with less drug toxicity. Results from an extended long-term study, with median
      follow-up of 63 mo, that investigated the role of MMF as continuous induction
      maintenance treatment for DPLN are presented. Thirty-three patients were
      randomized to receive MMF, and 31 were randomized to the CTX-AZA treatment arm,
      both in combination with prednisolone. More than 90% in each group responded
      favorably (complete or partial remission) to induction treatment. Serum
      creatinine in both groups remained stable and comparable over time. Creatinine
      clearance increased significantly in the MMF group, but the between-group
      difference was insignificant. Improvements in serology and proteinuria were
      comparable between the two groups. A total of 6.3% in the MMF group and 10.0% of
      CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up
      (P = 0.667). Both the relapse-free survival and the hazard ratio for relapse were
      similar between MMF- and CTX-AZA-treated patients (11 and nine patients relapsed,
      respectively) and between those with MMF treatment for 12 or >/=24 mo. MMF
      treatment was associated with fewer infections and infections that required
      hospitalization (P = 0.013 and 0.014, respectively). Four patients in the CTX-AZA
      group but none in the MMF group reached the composite end point of end-stage
      renal failure or death (P = 0.062 by survival analysis). It is concluded that MMF
      and prednisolone constitute an effective continuous induction-maintenance
      treatment for DPLN in Chinese patients.

PMID- 15728785
TI  - Reduced agonist-induced endothelium-dependent vasodilation in uremia is
      attributable to an impairment of vascular nitric oxide.
AB  - Current concepts for the explanation of endothelial dysfunction and accelerated
      atherosclerosis in uremia propose a reduced vascular bioavailability of nitric
      oxide (NO). The aim of the present study was to test the contributions of NO and
      NO/prostacyclin (PGI(2))-independent mechanisms to both baseline vascular tone
      and agonist-induced endothelium-dependent vasodilation in patients on
      hemodialysis (HD). In 10 HD patients and eight matched healthy control subjects,
      forearm blood flow (FBF) was measured at rest and during intrabrachial infusions
      of norepinephrine (NE; endothelium-independent vasoconstrictor, 60, 120, and 240
      pmol/min) and N-monomethyl-L-arginine (blocker of NO synthases, 16 micromol/min).
      After inhibition of cyclo-oxygenase by ibuprofen (1200 mg orally), endothelium
      dependent and -independent vasodilation was assessed by infusion of acetylcholine
      (ACh; 1, 5, 10, 50, 100, and 300 nmol/min) and sodium-nitroprusside (2.5, 5, and
      10 microg/min). NO/PGI(2)-independent vasodilation was tested by equal infusions
      of ACh during NO clamp. N-monomethyl-L-arginine reduced resting FBF to a
      comparable degree in both groups. Vascular responses to ACh were reduced in HD (P
      = 0.003 versus control by ANOVA), whereas those to sodium nitroprusside were
      mainly at control level. Infusion of ACh during NO clamp caused a similar
      increment of FBF in both groups. NO-mediated vasodilation as calculated by the
      difference between ACh-induced responses without and with NO clamp was
      substantially impaired in HD (P < 0.001) compared with control. In HD patients,
      baseline NO-mediated arteriolar tone is at control level. This study provides
      first evidence that endothelial dysfunction of uremic patients as shown by
      reduced agonist-induced endothelium-dependent vasodilation is attributable to
      reduced stimulation of NO, whereas the NO/PGI(2)-resistant portion of ACh
      mediated vasodilation is unaffected.

PMID- 15728786
TI  - Activated injectable vitamin D and hemodialysis survival: a historical cohort
      study.
AB  - Patients with ESRD commonly experience secondary hyperparathyroidism, a condition
      primarily managed with activated injectable vitamin D. The biologic effects of
      vitamin D, however, are widespread, and it is possible that activated injectable
      vitamin D alters survival in ESRD. This hypothesis was tested in a historical
      cohort study of incident hemodialysis patients who lived throughout the United
      States between January 1996 and December 1999. The primary outcome was 2-yr
      survival among those who survived for at least 90 d after initiation of chronic
      hemodialysis. During this period, 51,037 chronic hemodialysis patients survived
      for at least 90 d from the initiation of hemodialysis, and in the ensuing 2 yr,
      37,173 received activated injectable vitamin D and 13,864 did not. At 2 yr,
      mortality rates were 13.8/100 person-years in the group that received injectable
      vitamin D compared with 28.6/100 person-years in the group that did not (P <
      0.001). Cox proportional hazards analyses adjusting for several potential
      confounders and examining injectable vitamin D therapy as a time-dependent
      exposure suggested that compared with patients who did not receive injectable
      vitamin D, the 2-yr survival advantage associated with the group that did receive
      injectable vitamin D was 20% (hazard ratio, 0.80; 95% confidence interval, 0.76
      to 0.83). The incidence of cardiovascular-related mortality was 7.6/100 person
      years in the injectable vitamin D group, compared with 14.6/100 person-years in
      the non-vitamin D group (P < 0.001). The benefit of injectable vitamin D was
      evident in 48 of 49 strata examined, including those with low serum levels of
      intact parathyroid hormone and elevated levels of serum calcium and phosphorus,
      situations in which injectable vitamin D is often withheld. Repeating the entire
      analysis using marginal structural models to adjust for time-dependent
      confounding by indication yielded a survival advantage of 26% (hazard ratio,
      0.74; 95% confidence interval, 0.71 to 0.79) associated with the injectable
      vitamin D group. In this historical cohort study, chronic hemodialysis patients
      in the group that received injectable vitamin D had a significant survival
      advantage over patients who did not. Randomized clinical trials would permit
      definitive conclusions.

PMID- 15728787
TI  - Regression of glomerulosclerosis with high-dose angiotensin inhibition is linked
      to decreased plasminogen activator inhibitor-1.
AB  - The potential and possible mechanisms for regression of existing
      glomerulosclerosis by angiotensin II type 1 receptor antagonist (AT1RA) and/or
      angiotensin I converting enzyme inhibitor (ACEI) were investigated. Adult male
      Sprague Dawley rats underwent 5/6 nephrectomy (Nx). Glomerulosclerosis was
      assessed by renal biopsy 8 wk later, and rats were divided into groups with equal
      biopsy sclerosis and treated for the next 4 wk until they were killed at 12 wk as
      follows: Control with no further treatment (CONT), high-dose AT1RA, high-dose
      ACEI, and varying AT1RA+ACEI combinations. Hypertension and proteinuria induced
      by 5/6 Nx were significantly decreased by all treatments, except high-dose ACEI,
      which showed persistent proteinuria. High-dose AT1RA and ACEI markedly decreased
      progression of sclerosis, with -2.3% average decrease in sclerosis from biopsy to
      autopsy in AT1RA versus 194% increase in CONT (P < 0.0001). Glomerulosclerosis
      regressed, with less severe lesions at the time when the rats were killed than at
      biopsy in 62% of AT1RA-treated and 57% of ACEI-treated rats. In contrast, only 17
      to 33% of rats in combination groups had regression. Alternatively, these data
      might be viewed as reflecting halting of progression, as some groups had higher
      BP and proteinuria. However, this potential confounding effect does not negate
      the effects to achieve regression of sclerosis in these rats. Regression was not
      explained by changes in mRNA of TGF-beta1 and matrix metalloproteinase-2 and -9
      but was linked to decreased tissue inhibitor of metalloproteinase-1 and
      plasminogen activator inhibitor-1. It is concluded that angiotensin inhibition
      mediates regression in part by effects on matrix modulation.

PMID- 15728788
TI  - Role of the renin-angiotensin system on the parathyroid hormone-related protein
      overexpression induced by nephrotoxic acute renal failure in the rat.
AB  - Parathyroid hormone-related protein (PTHrP), a mitogenic factor for renal cells,
      is overexpressed in acute renal failure (ARF). Recent data support an association
      between PTHrP and the renin-angiotensin system in the damaged kidney. The effects
      of angiotensin II (Ang II) inhibitors (quinapril, enalapril, and/or losartan) on
      PTHrP and the PTH1 receptor (PTH1R) expression in rats with either folic acid
      (FA)- or gentamicin-induced ARF were analyzed. The decreased renal function and
      the PTHrP upregulation and PTH1R downregulation induced by the nephrotoxins were
      inhibited by the Ang II blockers. In tubuloepithelial cells NRK-52E, the rapid
      (10 min) increase in PTHrP mRNA by FA, associated with a perinuclear
      relocalization of Ang II/AT1 receptor, was inhibited by losartan but not
      candesartan, which traps Ang II receptors at the cell surface. Maximal PTHrP
      protein overexpression by FA (at 24 to 72 h)-or by exogenous Ang II-was abolished
      by both Ang II antagonists. PTHrP upregulation by FA was preceded by increased
      extracellular signal-regulated kinase (ERK) phosphorylation and inhibited by the
      ERK inhibitor PD098059. FA also activated cAMP response element-binding (CREB)
      protein, and this was prevented by losartan in these cells. Moreover, PTHrP mRNA
      overexpression by either FA or Ang II occurred in NRK 52E that were transfected
      with a CREB construct but not the dominant-negative CREB133 construct. These
      findings demonstrate that the decreased renal function and PTHrP overexpression
      in nephrotoxin-damaged kidney depends on renin-angiotensin system. In this
      setting, intracellular Ang II/AT1 receptor recycling seems to be related to PTHrP
      induction through ERK and CREB activation in tubuloepithelial cells.

PMID- 15728789
TI  - Daily or intermittent calcitriol administration during growth hormone therapy in
      rats with renal failure and advanced secondary hyperparathyroidism.
AB  - Growth hormone (GH) improves growth in children with chronic renal failure. The
      response to GH may be affected by the degree of secondary hyperparathyroidism and
      concurrent treatment with vitamin D. Forty-six rats underwent 5/6 nephrectomy
      (Nx) and were given a high-phosphorus diet (Nx-Phos) to induce advanced secondary
      hyperparathyroidism and divided into the following groups: (1) Nx-Phos (n = 10)
      received saline, (2) GH at 10 IU/kg per d (Nx-Phos+GH; n = 9), (3) GH and daily
      calcitriol (D) at 50 ng/kg per d (Nx-Phos+GH+daily D; n = 8), (4) GH and
      intermittent D (three times weekly) at 350 ng/kg per wk (Nx-Phos+GH+int D; n =
      9), and (5) intact-control (n = 10). Serum parathyroid hormone (PTH) levels were
      elevated in Nx-Phos, but IGF-I levels did not change with growth hormone. Body
      length, tibial length, and growth plate width did not increase with either GH or
      calcitriol. Proliferating cell nuclear antigen staining, PTH/PTHrP receptor, bone
      morphogenetic protein-7, and fibroblast growth factor receptor-3 expression
      increased with GH alone or with intermittent calcitriol but were slightly
      diminished during daily calcitriol administration. GH enhanced IGF-I, IGF binding
      receptor-3, and GH receptor but declined with daily and intermittent calcitriol.
      Overall, there was no improvement in body length, tibial length, and growth plate
      width at the end of GH therapy, but selected markers of chondrocyte proliferation
      and chondrocyte differentiation increased, although these changes were attenuated
      by calcitriol. The combination of GH and calcitriol that is frequently used in
      children with renal failure and secondary hyperparathyroidism require further
      studies to evaluate the optimal dose and frequency of administration to increase
      linear growth and prevent bone disease.

PMID- 15728791
TI  - Steroid hormones regulate gene expression posttranscriptionally by altering the
      stabilities of messenger RNAs.
AB  - Hormones exert powerful effects on reproductive physiology by regulating gene
      expression. Recent discoveries in hormone action emphasize that regulation of
      gene expression is not restricted to their alterations of the rate of gene
      transcription. On the contrary, hormonal effects on the stability of a specific
      mRNA can profoundly alter its steady-state concentration. The mRNAs encoding
      hormone receptors are commonly regulated by their own hormones to create
      autoregulatory feedback loops. Negative and positive autoregulatory feedback
      loops serve to limit or augment hormonal responses, respectively. After
      introducing the topics of mRNA degradation and regulated stability, this review
      focuses on steroid hormone effects on mRNA stabilities. Autoregulation of the
      mRNAs encoding estrogen, progesterone, androgen, and glucocorticoid receptors by
      the steroid hormones in reproductive tissues is discussed. In addition, steroid
      hormone effects on the stabilities of many other mRNAs that are important to
      reproductive biology are reviewed. These include mRNAs that encode gonadotropin
      hormones, integrins, growth factors, and inflammatory response proteins. Through
      these posttranscriptional effects, steroid hormones impact the expression of a
      large population of genes. Studies of the molecular mechanisms of hormonally
      regulated mRNA stabilities continue to identify critical mRNA sequence elements
      and their interactions with proteins. Increased understanding of how hormones
      affect mRNA stability may yield novel approaches to the therapeutic control of
      hormone effects, including those essential to reproductive physiology in animals.

PMID- 15728790
TI  - Cell-cycle inhibitors p27Kip1 and p21Cip1 regulate murine Sertoli cell
      proliferation.
AB  - Thyroid hormone inhibits neonatal Sertoli cell proliferation and recent results
      have shown that thyroid hormone upregulates cyclin-dependent kinase inhibitors
      (CDKIs) p27Kip1 and p21Cip1 (also known as CDKN1B and CDKN1A, respectively) in
      neonatal Sertoli cells. This suggests that these CDKIs, which negatively regulate
      the cell cycle, could be critical in Sertoli cell proliferation. Consistent with
      this hypothesis, mice lacking p27Kip1 develop testicular organomegaly, but
      Sertoli cell numbers have not been determined. Likewise, effects of loss of
      p21Cip1 or both p27 and p21 on Sertoli cell number and testicular development
      were unknown. To determine if p27 and/or p21 regulate Sertoli cell proliferation,
      we measured Sertoli cell proliferation at Postnatal Day 16 and testis weight,
      Sertoli cell number, and daily sperm production (DSP) in 4-mo-old wild-type (WT),
      p21 knockout (p21KO), p27 knockout (p27KO), and p27/p21 double-knockout (DBKO)
      mice. Testis weights were increased 27%, 42%, and 86% in adult p21KO, p27KO, and
      DBKO mice, respectively, compared with WT. Sertoli cell number also was increased
      48%, 126%, and 126% in p21KO, p27KO, and DBKO mice, respectively, versus WT. DSP
      in p21KO, p27KO, and DBKO testes also showed significant increases compared with
      WT mice. Although DSP was increased, there were increased spermatogenic defects
      observed in both p27KO and DBKO mice compared with WT. These data indicate that
      both p27 and p21 play an inhibitory role in regulating adult Sertoli cell number
      such that loss of either CDKI produces primary increases in Sertoli cell number
      and secondary increases in DSP and testis weight. Furthermore, loss of both CDKIs
      causes additive effects on DSP and testis weight, suggesting a central role for
      these CDKIs in testis development.

PMID- 15728792
TI  - Gene expression profiling following in utero exposure to phthalate esters reveals
      new gene targets in the etiology of testicular dysgenesis.
AB  - Male reproductive tract abnormalities associated with testicular dysgenesis in
      humans also occur in male rats exposed gestationally to some phthalate esters. We
      examined global gene expression in the fetal testis of the rat following in utero
      exposure to a panel of phthalate esters. Pregnant Sprague-Dawley rats were
      treated by gavage daily from Gestational Days 12 through 19 with corn oil vehicle
      (1 ml/kg) or diethyl phthalate (DEP), dimethyl phthalate (DMP), dioctyl tere
      phthalate (DOTP), dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP),
      dipentyl phthalate (DPP), or benzyl butyl phthalate (BBP) at 500 mg/kg per day.
      Testes were isolated on Gestational Day 19, and global changes in gene expression
      were determined. Of the approximately 30 000 genes queried, expression of 391
      genes was significantly altered following exposure to the developmentally toxic
      phthalates (DBP, BBP, DPP, and DEHP) relative to the control. The developmentally
      toxic phthalates were indistinguishable in their effects on global gene
      expression. No significant changes in gene expression were detected in the
      nondevelopmentally toxic phthalate group (DMP, DEP, and DOTP). Gene pathways
      disrupted include those previously identified as targets for DBP, including
      cholesterol transport and steroidogenesis, as well as newly identified pathways
      involved in intracellular lipid and cholesterol homeostasis, insulin signaling,
      transcriptional regulation, and oxidative stress. Additional gene targets include
      alpha inhibin, which is essential for normal Sertoli cell development, and genes
      involved with communication between Sertoli cells and gonocytes. The common
      targeting of these genes by a select group of phthalates indicates a role for
      their associated molecular pathways in testicular development and offers new
      insight into the molecular mechanisms of testicular dysgenesis.

PMID- 15728794
TI  - Zebrafish gonadotropins and their receptors: II. Cloning and characterization of
      zebrafish follicle-stimulating hormone and luteinizing hormone subunits--their
      spatial-temporal expression patterns and receptor specificity.
AB  - Gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)
      play critical roles in vertebrate reproduction. In the present study, we cloned
      and characterized zebrafish FSHbeta (fshb), LHbeta (lhb), and GTHalpha (cga)
      subunits. Compared with the molecules of other teleosts, the cysteine residues
      and potential glycosylation sites are fully conserved in zebrafish Lhb and Cga
      but not in Fshb, whose cysteines exhibit unique distribution. Interestingly, in
      addition to the pituitary, fshbeta, lhbeta, and cga were also expressed in some
      extrapituitary tissues, particularly the gonads and brain. In situ hybridization
      showed that zebrafish fshbeta and lhbeta were expressed in two distinct
      populations of gonadotrophs in the pituitary. Real-time reverse transcription
      polymerase chain reaction (RT-PCR) analysis revealed that all the three subunits
      increased expression before ovulation (0100-0400) when the germinal vesicles in
      the full-grown follicles were migrating toward the periphery, but the levels
      dropped at 0700, when ovulation occurred. Recombinant zebrafish FSH (zfFSH) and
      LH (zfLH) were produced in the Chinese hamster ovary (CHO) cells and their
      effects on the cognate receptors (zebrafish Fshr and Lhr) tested. Interestingly,
      zfFSH specifically activated zebrafish Fshr expressed together with a cAMP
      responsive reporter gene in the CHO cells, whereas zfLH could stimulate both Fshr
      and Lhr. In conclusion, the present study systematically investigated
      gonadotropins in the zebrafish in terms of their structure, spatial-temporal
      expression patterns, and receptor specificity. These results, together with the
      availability of recombinant zfFSH and zfLH, provide a solid foundation for
      further studies on the physiological relevance of FSH and LH in the zebrafish,
      one of the top biological models in vertebrates.

PMID- 15728793
TI  - Angiotensin II elevates nitric oxide synthase 3 expression and nitric oxide
      production via a mitogen-activated protein kinase cascade in ovine fetoplacental
      artery endothelial cells.
AB  - Normal pregnancy is associated with high angiotensin II (ANG II) concentrations
      in the maternal and fetal circulation. These high levels of ANG II may promote
      production vasodilators such as nitric oxide (NO). ANG II receptors are expressed
      in ovine fetoplacental artery endothelial (OFPAE) cells and mediate ANG II
      stimulated OFPAE cell proliferation. Herein, we tested whether ANG II stimulated
      NO synthase 3 (NOS3, also known as eNOS) expression and total NO (NO(x))
      production via activation of mitogen-activated protein kinase 3/1 (MAPK3/1, also
      known as ERK1/2) in OFPAE cells. ANG II elevated (P < 0.05) eNOS protein, but not
      mRNA levels with a maximum effect at 10 nM. ANG II also dose dependently
      increased (P < 0.05) NO(x) production with a maximal effect at doses of 1-100 nM.
      Activation of ERK1/2 by ANG II was determined by immunocytochemistry and Western
      blot analysis. ANG II rapidly induced positive staining for phosphorylated
      ERK1/2, appearing in cytosol after 1-5 min of ANG II treatment, accumulating in
      nuclei after 10 min, and disappearing at 15 min. ANG II increased (P < 0.05)
      phosphorylated ERK1/2 protein levels. Activation of ERK1/2 was confirmed by an
      immunocomplex kinase assay using ELK1 as a substrate. PD98059 significantly
      inhibited ANG II-induced ERK1/2 activation, and the ANG II-elevated eNOS protein
      levels but only partially reduced ANG II-increased NO(x) production. Thus, in
      OFPAE cells, the ANG II increased NO(x) production is associated with elevated
      eNOS protein expression, which is mediated at least in part via activation of the
      mitogen-activated protein kinase kinase1 and kinase2 (MAP2K1 and MAP2K2, known
      also as MEK1/2)/ERK1/2 cascade. Together with our previous observation that ANG
      II stimulates OFPAE cell proliferation, these data suggest that ANG II is a key
      regulator for both vasodilation and angiogenesis in the ovine fetoplacenta.

PMID- 15728795
TI  - Zebrafish gonadotropins and their receptors: I. Cloning and characterization of
      zebrafish follicle-stimulating hormone and luteinizing hormone receptors-
      evidence for their distinct functions in follicle development.
AB  - In the present study, we cloned and characterized zebrafish FSH receptor (Fshr)
      and LH receptor (Lhr). Both fshr and lhr were abundantly expressed in the
      zebrafish gonads; however, they could also be detected in the kidney and liver,
      respectively. When overexpressed in mammalian cell lines together with a cAMP
      responsive reporter gene, zebrafish Fshr responded to goldfish pituitary extract
      but not hCG, whereas Lhr could be activated by both. It was further demonstrated
      that Fshr was specific to bFSH, while Lhr could be stimulated by both bovine FSH
      and LH. Low level of fshr expression could be detected in the immature ovary, but
      the level steadily increased during vitellogenesis of the first cohort of
      developing follicles. In contrast, the expression of lhr could barely be detected
      in the immature ovary, but it became detectable at the beginning of
      vitellogenesis and steadily increased afterward with the peak level reached at
      the full-grown stage. At the follicle level, the expression of fshr was very weak
      in the follicles of primary growth stage but significantly increased with the
      follicles entering vitellogenesis. However, after reaching the maximal level in
      the midvitellogenic follicles, the level of fshr expression dropped slightly but
      significantly at the full-grown stage. In comparison, the expression of lhr
      obviously lagged behind that of fshr. Its expression became detectable only when
      the follicles started to accumulate yolk granules, but the level rose steadily
      afterward and reached the peak at the full-grown stage before oocyte maturation.
      These results suggest differential roles for Fshr and Lhr in zebrafish ovarian
      follicle development.

PMID- 15728796
TI  - Spatiotemporal expression of heparanase during human and rodent ovarian
      folliculogenesis.
AB  - Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate
      proteoglycans (HSPGs), major components of the basement membrane (BM) and
      extracellular matrix (ECM). Heparanase activity results in release of HSPG-bound
      molecules, including basic fibroblast growth factor (FGF2). Structural and
      functional development of the corpus luteum (CL) involves tissue remodeling,
      active angiogenesis, and steroid production. Heparanase-induced ECM and BM
      breakdown as well as FGF2-stimulated endothelial proliferation may have an
      important role in the regulation of luteal function. Heparanase mRNA was detected
      by reverse-transcription-polymerase chain reaction in granulosa cells recovered
      from follicular fluid of in vitro fertilization patients. Using sulfate-labeled
      ECM, heparanase enzymatic activity was determined in human luteinized granulosa
      cells. Employing immunohistochemistry, heparanase protein was localized
      predominantly in the theca interna cell layer of the mature antral follicle,
      whereas in human corpora lutea, both luteinized granulosa and theca cells were
      immunostained for heparanase. During luteolysis, heparanase was identified in
      macrophages surrounding the forming corpus albicans. In serially sectioned
      ovaries from unstimulated rats as well as from eCG-treated rats, expression of
      heparanase was noted exclusively in the ovarian steroid-producing interstitial
      tissue. Following an ovulatory dose of hCG, heparanase was immunostained also in
      lutein cells of the forming corpora lutea. Temporal expression of heparanase in
      granulosa cells during the luteal phase and in macrophages during luteal
      regression supports the hypothesis that heparanase plays a role in human ovarian
      ECM remodeling and may potentiate cellular migration and growth factor
      bioavailability.

PMID- 15728798
TI  - A novel and efficient approach to discriminate between pre- and post
      transcription HIV inhibitors.
AB  - Established anti-human immunodeficiency virus (HIV) treatments are not always
      effective or well tolerated, highlighting the need for further refinement of
      antiviral drug design and development. Given the multitude of molecular targets
      with which the anti-HIV agents can interact, studies on the mechanism of action
      of newly discovered HIV inhibitors are quite elaborate. In this article, we
      describe the use of an efficient reporter system allowing rapid discrimination
      between a pre- or post-transcriptional mode of action of anti-HIV compounds based
      on infection by a replication competent HIV-1 molecular clone expressing the
      green fluorescent protein as part of the nef multiply spliced RNA. Using
      fluorescence microscopy and flow cytometry, this system enabled us to
      differentiate between compounds acting at a pre- or post-transciptional level of
      the virus life cycle. Antiviral activities were determined for four reference
      compounds as well as one putative novel HIV inhibitor. The results obtained were
      in agreement with the known characteristics of the reference compounds and
      revealed that the novel compound interfered with a target before or overlapping
      with HIV transcription. We showed that during a single replication cycle,
      compounds inhibiting a molecular target occurring before or coinciding with HIV
      transcription suppressed GFP expression, whereas compounds interfering at a later
      stage (such as protease inhibitors, which act after transcription) did not
      inhibit GFP expression. This GFP-based reporter system is adaptable for high
      throughput screening.

PMID- 15728799
TI  - Stiff competition.

PMID- 15728800
TI  - The two faces of leptin.

PMID- 15728801
TI  - Meeting report: 4th European Congress of Biogerontology.
AB  - The 4th European Congress of Biogerontology took place in Newcastle upon Tyne in
      November 2004. Leading figures in the biology of aging presented their recent
      work, providing new insights into fundamental mechanisms of aging as it occurs in
      organisms ranging from yeast to the human species. Highlights of these
      presentations are presented here.

PMID- 15728802
TI  - A new biogerontology lab in newcastle.
AB  - The Henry Wellcome Laboratory for Biogerontology Research has opened at the
      University of Newcastle upon Tyne. The official opening followed the 4th European
      Congress of Biogerontology and was witnessed by many of its participants as well
      as a few special guests.

PMID- 15728803
TI  - Images in clinical medicine. Malposition of a Sengstaken-Blakemore tube.

PMID- 15728804
TI  - Generic HIV drugs--enlightened policy for global health.

PMID- 15728805
TI  - Geriatrics in the United States--baby boomers' boon?

PMID- 15728806
TI  - Sixth disease and the ubiquity of human herpesviruses.

PMID- 15728807
TI  - Bearing witness--Sontag and the body.

PMID- 15728808
TI  - Effectiveness of mass oral cholera vaccination in Beira, Mozambique.
AB  - BACKGROUND: New-generation, orally administered cholera vaccines offer the
      promise of improved control of cholera in sub-Saharan Africa. However, the high
      prevalence of human immunodeficiency virus (HIV) infection in many cholera
      affected African populations has raised doubts about the level of protection
      possible with vaccination. We evaluated a mass immunization program with
      recombinant cholera-toxin B subunit, killed whole-cell (rBS-WC) oral cholera
      vaccine in Beira, Mozambique, a city where the seroprevalence of HIV is 20 to 30
      percent. METHODS: From December 2003 to January 2004, we undertook mass
      immunization of nonpregnant persons at least two years of age, using a two-dose
      regimen of rBS-WC vaccine in Esturro, Beira (population 21,818). We then assessed
      vaccine protection in a case-control study during an outbreak of El Tor Ogawa
      cholera in Beira between January and May 2004. To estimate the level of vaccine
      protection, antecedent rates of vaccination were compared between persons with
      culture-confirmed cholera severe enough to have prompted them to seek treatment
      and age- and sex-matched neighborhood controls without treated diarrhea. RESULTS:
      We assessed the effectiveness of the vaccine in 43 persons with cholera and 172
      controls. Receipt of one or more doses of rBS-WC vaccine was associated with 78
      percent protection (95 percent confidence interval, 39 to 92 percent; P=0.004).
      The vaccine was equally effective in children younger than five years of age and
      in older persons. A concurrently conducted case-control study designed to detect
      bias compared persons with treated, noncholeraic diarrhea and controls without
      diarrhea in the same population and found no protection associated with receipt
      of the rBS-WC vaccine. CONCLUSIONS: The rBS-WC vaccine was highly effective
      against clinically significant cholera in an urban sub-Saharan African population
      with a high prevalence of HIV infection.

PMID- 15728809
TI  - A population-based study of primary human herpesvirus 6 infection.
AB  - BACKGROUND: Serologic studies indicate that human herpesvirus 6 (HHV-6) infects
      90 percent of children by two years of age. Little is known about the
      acquisition, virologic course, and clinical manifestations of HHV-6 infection.
      METHODS: We prospectively studied a cohort of 277 children from birth through the
      first two years of life to define the pattern of acquisition of HHV-6. The
      children's saliva was tested weekly for HHV-6 DNA with the use of the polymerase
      chain reaction. Parents maintained a daily log of signs and symptoms of illness
      in their children. RESULTS: Primary HHV-6 infection occurred in 130 children,
      with cumulative percentages of 40 percent by the age of 12 months and 77 percent
      by the age of 24 months. The peak age of acquisition was between 9 and 21 months.
      The acquisition of HHV-6 was associated with female sex (adjusted hazard ratio,
      1.7; 95 percent confidence interval, 1.2 to 2.4) and having older siblings
      (adjusted hazard ratio, 2.1; 95 percent confidence interval, 1.4 to 2.9). Among
      81 children with a well-defined time of acquisition of HHV-6, 93 percent had
      symptoms, and 38 percent were seen by a physician. None had seizures. As compared
      with children who had other illnesses, those with primary HHV-6 infection were
      more likely to have fever (P=0.003), fussiness (P=0.02), diarrhea (P=0.03), rash
      (P=0.003), and roseola (P=0.002) and were more likely to visit a physician
      (P=0.003). CONCLUSIONS: The acquisition of HHV-6 in infancy is usually
      symptomatic and often results in medical evaluation. Roseola occurs in a minority
      of patients, and febrile seizures are infrequently associated with primary HHV-6
      infection. Older siblings appear to serve as a source of HHV-6 transmission.

PMID- 15728810
TI  - Recombinant activated factor VII for acute intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is
      associated with high mortality. Among patients who undergo computed tomography
      (CT) within three hours after the onset of intracerebral hemorrhage, one third
      have an increase in the volume of the hematoma related to subsequent bleeding. We
      sought to determine whether recombinant activated factor VII (rFVIIa) can reduce
      hematoma growth after intracerebral hemorrhage. METHODS: We randomly assigned 399
      patients with intracerebral hemorrhage diagnosed by CT within three hours after
      onset to receive placebo (96 patients) or 40 microg of rFVIIa per kilogram of
      body weight (108 patients), 80 microg per kilogram (92 patients), or 160 microg
      per kilogram (103 patients) within one hour after the baseline scan. The primary
      outcome measure was the percent change in the volume of the intracerebral
      hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS:
      Hematoma volume increased more in the placebo group than in the rFVIIa groups.
      The mean increase was 29 percent in the placebo group, as compared with 16
      percent, 14 percent, and 11 percent in the groups given 40 microg, 80 microg, and
      160 microg of rFVIIa per kilogram, respectively (P=0.01 for the comparison of the
      three rFVIIa groups with the placebo group). Growth in the volume of
      intracerebral hemorrhage was reduced by 3.3 ml, 4.5 ml, and 5.8 ml in the three
      treatment groups, as compared with that in the placebo group (P=0.01). Sixty-nine
      percent of placebo-treated patients died or were severely disabled (as defined by
      a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49
      percent, and 54 percent of the patients who were given 40, 80, and 160 microg of
      rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with
      the placebo group). Mortality at 90 days was 29 percent for patients who received
      placebo, as compared with 18 percent in the three rFVIIa groups combined
      (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral
      infarction, occurred in 7 percent of rFVIIa-treated patients, as compared with 2
      percent of those given placebo (P=0.12). CONCLUSIONS: Treatment with rFVIIa
      within four hours after the onset of intracerebral hemorrhage limits the growth
      of the hematoma, reduces mortality, and improves functional outcomes at 90 days,
      despite a small increase in the frequency of thromboembolic adverse events.

PMID- 15728811
TI  - EGFR mutation and resistance of non-small-cell lung cancer to gefitinib.
AB  - Mutations of the epidermal growth factor receptor (EGFR) gene have been
      identified in specimens from patients with non-small-cell lung cancer who have a
      response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to
      such inhibitors, most patients ultimately have a relapse. The mechanism of the
      drug resistance is unknown. Here we report the case of a patient with EGFR
      mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a
      relapse after two years of complete remission during treatment with gefitinib.
      The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse
      revealed the presence of a second point mutation, resulting in threonine-to
      methionine amino acid change at position 790 of EGFR. Structural modeling and
      biochemical studies showed that this second mutation led to gefitinib resistance.

PMID- 15728812
TI  - Clinical practice. Rosacea.

PMID- 15728813
TI  - Chronic lymphocytic leukemia.

PMID- 15728814
TI  - Images in clinical medicine. Corkscrew esophagus.

PMID- 15728815
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 6-2005. A 58-year-old man with esophageal cancer and nausea,
      vomiting, and intractable hiccups.

PMID- 15728816
TI  - Disaster, water, cholera, vaccines, and hope.

PMID- 15728817
TI  - Stopping the bleeding in intracerebral hemorrhage.

PMID- 15728818
TI  - Chasing mutations in the epidermal growth factor in lung cancer.

PMID- 15728819
TI  - Preventing microalbuminuria in type 2 diabetes.

PMID- 15728820
TI  - Telmisartan vs. enalapril in type 2 diabetes.

PMID- 15728821
TI  - Prostanoid DP receptor variants and asthma.

PMID- 15728822
TI  - Medical research and the news media.

PMID- 15728823
TI  - Neonatal brain injury.

PMID- 15728824
TI  - Multiple myeloma.

PMID- 15728825
TI  - Getting the lead out.

PMID- 15728826
TI  - APL during gefitinib treatment for non-small-cell lung cancer.

PMID- 15728827
TI  - Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in
      brain development and homeostasis.
AB  - A new technique based on diffusion tensor imaging and computational neuroanatomy
      was developed to efficiently and quantitatively characterize the three
      dimensional morphology of the developing brains. The technique was used to
      analyze the phenotype of conditional Bcl-x knock-out mice, in which the bcl-x
      gene was deleted specifically in neurons of the cerebral cortex and hippocampus
      beginning at embryonic day 13.5 as cells became postmitotic. Affected brain
      regions and associated axonal tracts showed severe atrophy in adult Bcl-x
      deficient mice. Longitudinal studies revealed that these phenotypes are
      established by regressive processes that occur primarily during the first
      postnatal week, whereas neurogenesis and migration showed no obvious abnormality
      during embryonic stages. Specific families of white matter tracts that once
      formed normally during the embryonic stages underwent dramatic degeneration
      postnatally. Thus, this technique serves as a powerful tool to efficiently
      localize temporal and spatial manifestation of morphological phenotype.

PMID- 15728828
TI  - Identification of a dopamine transporter ligand that blocks the stimulant effects
      of cocaine.
AB  - There is a large unmet medical need for cocaine addiction treatments. Studies
      have indicated that the dopamine transporter (DAT) is the primary biological
      target of cocaine, and most drugs that have DAT affinity have behavioral effects
      like those of cocaine. However, analogs of benztropine have high DAT affinity and
      behavioral effects that show varying degrees of similarity to cocaine. We now
      report the discovery that a benztropine analog, JHW007, with high affinity for
      the DAT does not have cocaine-like behavioral effects and antagonizes the effects
      of cocaine. JHW007 occupied the DAT in vivo more slowly than did cocaine and had
      not reached an apparent plateau up to 270 min after injection. The in vivo
      binding of cocaine to the DAT suggested rate of DAT occupancy as an important
      contributor to its behavioral effects, and the slow association with the DAT may
      provide an explanation for JHW007 being relatively devoid of cocaine-like
      behavioral effects. The antagonism of cocaine suggests that DAT ligands with
      reduced cocaine-like activity can function as cocaine antagonists and suggests
      JHW007 as a lead for discovery of cocaine-abuse pharmacotherapeutics.

PMID- 15728829
TI  - Beta1,3-N-acetylglucosaminyltransferase 1 glycosylation is required for axon
      pathfinding by olfactory sensory neurons.
AB  - During embryonic development, axons from sensory neurons in the olfactory
      epithelium (OE) extend into the olfactory bulb (OB) where they synapse with
      projection neurons and form glomerular structures. To determine whether glycans
      play a role in these processes, we analyzed mice deficient for the
      glycosyltransferase beta1,3-N-acetylglucosaminyltransferase 1 (beta3GnT1), a key
      enzyme in lactosamine glycan synthesis. Terminal lactosamine expression, as shown
      by immunoreactivity with the monoclonal antibody 1B2, is dramatically reduced in
      the neonatal null OE. Postnatal beta3GnT1-/- mice exhibit severely disorganized
      OB innervation and defective glomerular formation. Beginning in embryonic
      development, specific subsets of odorant receptor-expressing neurons are
      progressively lost from the OE of null mice, which exhibit a postnatal smell
      perception deficit. Axon guidance errors and increased neuronal cell death result
      in an absence of P2, I7, and M72 glomeruli, indicating a reduction in the
      repertoire of odorant receptor-specific glomeruli. By approximately 2 weeks of
      age, lactosamine is unexpectedly reexpressed in sensory neurons of null mice
      through a secondary pathway, which is accompanied by the regrowth of axons into
      the OB glomerular layer and the return of smell perception. Thus, both neonatal
      OE degeneration and the postnatal regeneration are lactosamine dependent.
      Lactosamine expression in beta3GnT1-/- mice is also reduced in pheromone
      receptive vomeronasal neurons and dorsal root ganglion cells, suggesting that
      beta3GnT1 may perform a conserved function in multiple sensory systems. These
      results reveal an essential role for lactosamine in sensory axon pathfinding and
      in the formation of OB synaptic connections.

PMID- 15728830
TI  - Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection
      mediated by blockade of microglial activation.
AB  - Alzheimer's disease (AD) is characterized by enhanced beta-amyloid peptide
      (betaA) deposition along with glial activation in senile plaques, selective
      neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents
      against excitotoxicity in vitro and acute brain damage in vivo. This background
      prompted us to study the localization, expression, and function of cannabinoid
      receptors in AD and the possible protective role of cannabinoids after betaA
      treatment, both in vivo and in vitro. Here, we show that senile plaques in AD
      patients express cannabinoid receptors CB1 and CB2, together with markers of
      microglial activation, and that CB1-positive neurons, present in high numbers in
      control cases, are greatly reduced in areas of microglial activation. In
      pharmacological experiments, we found that G-protein coupling and CB1 receptor
      protein expression are markedly decreased in AD brains. Additionally, in AD
      brains, protein nitration is increased, and, more specifically, CB1 and CB2
      proteins show enhanced nitration. Intracerebroventricular administration of the
      synthetic cannabinoid WIN55,212-2 to rats prevent betaA-induced microglial
      activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU
      210, WIN55,212-2, and JWH-133) block betaA-induced activation of cultured
      microglial cells, as judged by mitochondrial activity, cell morphology, and tumor
      necrosis factor-alpha release; these effects are independent of the antioxidant
      action of cannabinoid compounds and are also exerted by a CB2-selective agonist.
      Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after betaA
      addition to rat cortical cocultures. Our results indicate that cannabinoid
      receptors are important in the pathology of AD and that cannabinoids succeed in
      preventing the neurodegenerative process occurring in the disease.

PMID- 15728831
TI  - A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of
      neuronal Ca2+ channels phosphorylated by protein kinase C.
AB  - Phosphorylation and dephosphorylation are primary means for rapid regulation of a
      variety of neuronal functions, such as membrane excitability, neurotransmitter
      release, and gene expression. Voltage-gated Ca2+ channels are targets for
      phosphorylation by a variety of second messengers through activation of different
      types of protein kinases (PKs). Protein phosphatases (PPs), like PKs, are equally
      important in regulating Ca2+ channels in neurons. However, much less is
      understood about whether and how a particular type of PP contributes to
      regulating neuronal Ca2+ channel activities. This is primarily because of the
      lack of specific inhibitors/activators for different types of PPs, particularly
      the PP2c family. The functional roles of PP2c and its substrates in the brain
      remain virtually unknown. During our yeast two-hybrid screening, PP2calpha was
      pulled out by both N- and P/Q-type Ca2+ channel C termini. This raised the
      possibility that PP2calpha might be associated with voltage-gated Ca2+ channels
      for regulation of the Ca(2+) channel activity. Biochemical studies show that
      PP2calpha binds directly to neuronal Ca2+ channels forming a functional protein
      complex in vivo. PP2calpha, unlike PP1, PP2a and PP2b, is more effective in
      dephosphorylation of neuronal Ca2+ channels after their phosphorylation by PKC.
      In hippocampal neurons, disruption of the PP2calpha-Ca2+ channel interaction
      significantly enhances the response of Ca2+ channels to modulation by PKC. Thus,
      the PP2calpha-Ca2+ channel complex is responsible for rapid dephosphorylation of
      Ca2+ channels and may contribute to regulation of synaptic transmission in
      neurons.

PMID- 15728832
TI  - Tonotopic specialization of auditory coincidence detection in nucleus laminaris
      of the chick.
AB  - The interaural time difference (ITD) is a cue for localizing a sound source along
      the horizontal plane and is first determined in the nucleus laminaris (NL) in
      birds. Neurons in NL are tonotopically organized, such that ITDs are processed
      separately at each characteristic frequency (CF). Here, we investigated the
      excitability and coincidence detection of neurons along the tonotopic axis in NL,
      using a chick brainstem slice preparation. Systematic changes with CF were
      observed in morphological and electrophysiological properties of NL neurons.
      These properties included the length of dendrites, the input capacitance, the
      conductance of hyperpolarization-activated current, and the EPSC time course. In
      contrast to these gradients, the conductance of low-threshold K+ current and the
      expression of Kv1.2 channel protein were maximal in the central (middle-CF)
      region of NL. As a result, the middle-CF neuron had the smallest input resistance
      and membrane time constant, and consequently the fastest EPSP, and exhibited the
      most accurate coincidence detection. The specialization of middle-CF neurons as
      coincidence detectors may account for the high resolution of sound-source
      localization in the middle-frequency range observed in avians.

PMID- 15728833
TI  - Memory reconsolidation engages only a subset of immediate-early genes induced
      during consolidation.
AB  - The relationship between memory consolidation and reconsolidation at the
      molecular level is poorly understood. Here, we identify three immediate-early
      genes that are differentially regulated in the mouse hippocampus after contextual
      fear conditioning and reactivation of the context-shock memory: serum- and
      glucocorticoid-induced kinase 1 (SGK1), SGK3, and nerve growth factor-inducible
      gene B (NGFI-B). The upregulation of SGK1 expression was not specific for the
      context-shock association and therefore not suitable for a comparison of
      contextual memory consolidation and reconsolidation. SGK3 expression was
      upregulated during both consolidation and reconsolidation. Analysis of SGK3
      expression showed that expression changes elicited by a context-shock association
      during consolidation can subsequently be recapitulated during reconsolidation and
      that the transcriptional changes induced by retrieval depend on the remoteness of
      the memory. On the other hand, we found that NGFI-B is regulated during
      consolidation but not reconsolidation. This consolidation-specific regulation
      occurs in hippocampal area CA1. Our discovery of a consolidation-specific
      transcription indicates that reconsolidation is only a partial recapitulation of
      consolidation at the transcriptional level. Such partial rather than total
      recapitulation may have evolved as a more economic and reliable mechanism for
      organisms to modify memory.

PMID- 15728834
TI  - Antiepileptic effects of botulinum neurotoxin E.
AB  - Experimental studies suggest that the delivery of antiepileptic agents into the
      seizure focus might be of potential utility for the treatment of focal-onset
      epilepsies. Botulinum neurotoxin E (BoNT/E) causes a prolonged inhibition of
      neurotransmitter release after its specific cleavage of the synaptic protein
      synaptosomal-associated protein of 25 kDa (SNAP-25). Here, we show that BoNT/E
      injected into the rat hippocampus inhibits glutamate release and blocks spike
      activity of pyramidal neurons. BoNT/E effects persist for at least 3 weeks, as
      determined by immunodetection of cleaved SNAP-25 and loss of intact SNAP-25. The
      delivery of BoNT/E to the rat hippocampus dramatically reduces both focal and
      generalized kainic acid-induced seizures as documented by behavioral and
      electrographic analysis. BoNT/E treatment also prevents neuronal loss and long
      term cognitive deficits associated with kainic acid seizures. Moreover, BoNT/E
      injected rats require 50% more electrical stimulations to reach stage 5 of
      kindling, thus indicating a delayed epileptogenesis. We conclude that BoNT/E
      delivery to the hippocampus is both antiictal and antiepileptogenic in
      experimental models of epilepsy.

PMID- 15728835
TI  - The HVC microcircuit: the synaptic basis for interactions between song motor and
      vocal plasticity pathways.
AB  - Synaptic interactions between telencephalic neurons innervating descending motor
      or basal ganglia pathways are essential in the learning, planning, and execution
      of complex movements. Synaptic interactions within the songbird telencephalic
      nucleus HVC are implicated in motor and auditory activity associated with learned
      vocalizations. HVC contains projection neurons (PNs) (HVC(RA)) that innervate
      song premotor areas, other PNs (HVC(X)) that innervate a basal ganglia pathway
      necessary for vocal plasticity, and interneurons (HVC(INT)). During singing,
      HVC(RA) fire in temporally sparse bursts, possibly because of HVC(INT)-HVC(RA)
      interactions, and a corollary discharge can be detected in the basal ganglia
      pathway, likely because of synaptic transmission from HVC(RA) to HVC(X) cells.
      During song playback, local interactions, including inhibition onto HVC(X) cells,
      shape highly selective responses that distinguish HVC from its auditory
      afferents. To better understand the synaptic substrate for the motor and auditory
      properties of HVC, we made intracellular recordings from pairs of HVC neurons in
      adult male zebra finch brain slices and used spike-triggered averages to assess
      synaptic connectivity. A major synaptic interaction between the PNs was a
      disynaptic inhibition from HVC(RA) to HVC(X), which could link song motor signals
      in the two outputs of HVC and account for some of the song playback-evoked
      inhibition in HVC(X) cells. Furthermore, single interneurons made divergent
      connections onto PNs of both types, and either PN type could form reciprocal
      connections with interneurons. In these two regards, the synaptic architecture of
      HVC resembles that described in some pattern-generating networks, underscoring
      features likely to be important to singing and song learning.

PMID- 15728836
TI  - Respiratory rhythm entrainment by somatic afferent stimulation.
AB  - Respiratory and locomotor patterns are coupled during locomotion. The objectives
      of this study were to (1) demonstrate that respiratory rhythms are entrained by
      sensory input from somatic afferents, (2) establish whether the parabrachial
      nucleus mediates entrainment, (3) examine responses of single respiratory neurons
      in the ventral respiratory group (VRG) to somatic afferent stimulation, and (4)
      use a computational model of the pontomedullary respiratory network (Rybak et
      al., 2004a,b) to suggest neuronal mechanisms for entrainment. We used an in situ
      preparation in young rats that retained pontomedullary respiratory circuits and
      spinal pathways transmitting somatosensory input. We demonstrate that rhythmic
      stimulation of somatic afferents entrains respiratory rhythm on a 1:1 basis
      (1:1), increasing breathing frequency up to approximately 1.4-2.2 times greater
      than spontaneous frequency. Stable entrainment occurred only when stimuli were
      delivered during expiration. Reversible blockade of the lateral parabrachial
      nucleus eliminated entrainment. Somatic afferent stimulation produced significant
      increases in the firing rate of augmenting expiratory (E2) neurons but shortened
      the firing duration of postinspiratory (post-I) neurons. A computational model
      reproduced 1:1 entrainment and other experimental findings based on the
      assumption that the somatic afferents initiate early onset of inspiration via
      activation of medullary E2 neurons. The model also predicted that afferent
      stimulation evoked transient hyperpolarization of ramp-inspiratory (ramp-I)
      neurons. This was confirmed experimentally by intracellular recording from ramp-I
      neurons. Our experimental and modeling results demonstrate that an entrainment
      pathway from somatic afferents to the VRG via the lateral parabrachial nucleus
      causes resetting of respiratory rhythm through excitation of E2 and consequent
      inhibition of post-I neurons.

PMID- 15728837
TI  - Persistent phosphorylation by protein kinase Mzeta maintains late-phase long-term
      potentiation.
AB  - Protein kinase Mzeta (PKMzeta), an autonomously active atypical PKC isoform, is
      both necessary and sufficient for enhanced synaptic transmission during long-term
      potentiation (LTP) maintenance. LTP, however, evolves through several temporal
      phases, which may be mediated by distinct molecular mechanisms of potentiation.
      Here, we determined the specific phase of LTP maintained by PKMzeta. Using a
      selective, cell-permeable zeta-pseudosubstrate inhibitor at concentrations that
      block potentiation produced by postsynaptic perfusion of PKMzeta, we inhibited
      PKMzeta activity at various times after tetanization of Schaffer
      collateral/commissural-CA1 synapses. Inhibition of PKMzeta did not affect
      baseline AMPA receptor-mediated synaptic transmission or an early phase of LTP.
      In contrast, the inhibitor reversed established LTP when applied 1, 3, or 5 h
      after tetanic stimulation. Control nontetanized pathways within the hippocampal
      slices were unaffected. An inactive scrambled version of the peptide had no
      effect on LTP. Thus, persistent, increased phosphorylation by PKMzeta
      specifically maintains the late phase of LTP.

PMID- 15728838
TI  - Locus ceruleus activation suppresses feedforward interneurons and reduces beta
      gamma electroencephalogram frequencies while it enhances theta frequencies in rat
      dentate gyrus.
AB  - The locus ceruleus is activated by novel stimuli, and its activation promotes
      learning and memory. Phasic activation of locus ceruleus neurons by glutamate
      enhances the dentate gyrus population spike amplitude and results in long-term
      potentiation of synaptic responses recorded after 24 h. Cholinergic activation of
      locus ceruleus neurons increases hippocampal . At the level of the cellular
      network, it is not clear how the potentiating effects of norepinephrine are
      mediated. Previous studies show that exogenous norepinephrine enhances inhibitory
      interneuron firing in the dentate gyrus. This finding appears at odds with
      evidence for potentiation. In this study, natural release of norepinephrine was
      induced by glutamate activation of locus ceruleus while we recorded EEGs and
      physiologically identified interneurons in the dentate gyrus of urethane
      anesthetized rats. Feedforward neurons were inhibited (approximately 1-2 min) by
      locus ceruleus activation. Feedback interneurons showed both increased and
      decreased activity, whereas granule cells increased firing as predicted by evoked
      potential studies. EEG results replicated an increase in power (4-8 Hz) with
      locus ceruleus activation, but the effect with glutamatergic locus ceruleus
      activation was transient (approximately 1-2 min). Beta-gamma Frequencies were
      also transiently suppressed. Together, the data suggest that locus ceruleus
      activation enhances the throughput of concomitant sensory input by reducing
      feedforward inhibitory interneuron activity, which may reduce "binding" in
      existing cell assemblies, and enhances the conditions for synaptic plasticity
      through disinhibition, promotion of 4-8 Hz , and noradrenergic potentiation to
      facilitate the building of new representations.

PMID- 15728839
TI  - Galantamine activates muscle-type nicotinic acetylcholine receptors without
      binding to the acetylcholine-binding site.
AB  - Galantamine (Reminyl; Janssen Pharmaceutica, Titusville, NJ) belongs to a class
      of acetylcholinesterase inhibitors approved for symptomatic treatment of
      Alzheimer's disease. The drug presumably acts by raising and prolonging the
      profile of acetylcholine (ACh) via an inhibitory effect on the esterase. However,
      there is also evidence demonstrating that galantamine can activate the nicotinic
      ACh receptor or modulate its activation by ACh. In this study, we have examined
      the ability of galantamine to directly activate the muscle-type nicotinic ACh
      receptor or to modulate receptor activation by selected nicotinic agonists.
      Studies of direct activation by galantamine demonstrated that this ligand is a
      low-efficacy agonist of the muscle-type ACh receptor. Point mutations in the M2
      M3 linker (alphaS269I) and the M2 transmembrane domain (epsilonT264P) had similar
      effects on receptor activation by galantamine and nicotinic agonists, suggesting
      that the general features of receptor activation by galantamine are similar to
      that in the presence of ACh. Experiments performed in the simultaneous presence
      of galantamine and various nicotinic ligands showed that channel activation by
      the nicotinic ligands studied (ACh, carbachol, and choline) was not affected by
      the presence of galantamine at concentrations up to 100 microm. In addition,
      galantamine did not reduce the initial rate of binding for 125I-alpha
      bungarotoxin. These results demonstrate that galantamine does not interfere with
      the occupation of the nicotinic agonist binding site by ACh, carbachol, or
      choline. We conclude that galantamine activates the muscle-type ACh receptor by
      interacting with a binding site that is distinct from the site for nicotinic
      agonists.

PMID- 15728840
TI  - Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin
      1: implications for Lewy body formation.
AB  - It is widely accepted that the familial Parkinson's disease (PD)-linked gene
      product, parkin, functions as a ubiquitin ligase involved in protein turnover via
      the ubiquitin-proteasome system. Substrates ubiquitinated by parkin are hence
      thought to be destined for proteasomal degradation. Because we demonstrated
      previously that parkin interacts with and ubiquitinates synphilin-1, we initially
      expected synphilin-1 degradation to be enhanced in the presence of parkin.
      Contrary to our expectation, we found that synphilin-1 is normally ubiquitinated
      by parkin in a nonclassical, proteasomal-independent manner that involves lysine
      63 (K63)-linked polyubiquitin chain formation. Parkin-mediated degradation of
      synphilin-1 occurs appreciably only at an unusually high parkin to synphilin-1
      expression ratio or when primed for lysine 48 (K48)-linked ubiquitination. In
      addition we found that parkin-mediated ubiquitination of proteins within Lewy
      body-like inclusions formed by the coexpression of synphilin-1, alpha-synuclein,
      and parkin occurs predominantly via K63 linkages and that the formation of these
      inclusions is enhanced by K63-linked ubiquitination. Our results suggest that
      parkin is a dual-function ubiquitin ligase and that K63-linked ubiquitination of
      synphilin-1 by parkin may be involved in the formation of Lewy body inclusions
      associated with PD.

PMID- 15728841
TI  - Differential postnatal maturation of GABAA, glycine receptor, and mixed synaptic
      currents in Renshaw cells and ventral spinal interneurons.
AB  - Renshaw cells (RCs) receive excitatory inputs from motoneurons to which then they
      inhibit. The gain of this spinal recurrent inhibitory circuit is modulated by
      inhibitory synapses on RCs. Inhibitory synapses on RCs mature postnatally,
      developing unusually large postsynaptic gephyrin clusters that colocalize glycine
      and GABA(A) receptors. We hypothesized that these features potentiate inhibitory
      currents in RCs. Thus, we analyzed glycinergic and GABAergic "inhibitory"
      miniature postsynaptic currents (mPSCs) in neonatal [postnatal day 1 (P1) to P5]
      and mature (P9-P15) RCs and compared them to other ventral interneurons (non
      RCs). Recorded neurons were Neurobiotin filled and identified as RCs or non-RCs
      using post hoc immunohistochemical criteria. Glycinergic, GABAergic, and mixed
      glycine/GABA mPSCs matured differently in RCs and non-RCs. In RCs, glycinergic
      and GABA(A) mPSC peak amplitudes increased 230 and 45%, respectively, from P1-P5
      to P9-P15, whereas in non-RCs, glycinergic peak amplitudes changed little and
      GABA(A) amplitudes decreased. GABA(A) mPSCs were slower in RCs (P1-P5, tau = 58
      ms; P9-P15, tau = 43 ms) compared with non-RCs (P1-P5, tau = 27 ms; P9-P15, tau =
      14 ms). Thus, fast glycinergic currents dominated "mixed" mPSC peak amplitudes in
      mature RCs, and GABA(A) currents dominated their long decays. In non-RCs,
      GABAergic and mixed events had shorter durations, and their frequencies decreased
      with development. Functional maturation of inhibitory synapses on RCs correlates
      well with increased glycine receptor recruitment to large gephyrin patches,
      colocalization with alpha3/alpha5-containing GABA(A) receptors, and maintenance
      of GABA/glycine corelease. As a result, charge transfer in GABA, glycine, or
      mixed mPSCs was larger in mature RCs than in non-RCs, suggesting RCs receive
      potent inhibitory synapses.

PMID- 15728842
TI  - NMDA receptors increase the size of GABAergic terminals and enhance GABA release.
AB  - In developing cerebellar interneurons, NMDA increases spontaneous GABA release by
      activating presynaptic NMDA receptors. We investigated the role of these
      receptors on differentiating basket/stellate cells in cerebellar cultures grown
      under conditions allowing functional synaptic transmission. Presynaptic GABAergic
      boutons were visualized either by GAD65 immunostaining or by using cells derived
      from GAD65-enhanced green fluorescent protein (eGFP) transgenic mice, in which
      cerebellar basket/stellate cells express eGFP. After the first week in culture,
      whole-cell recordings from granule cells reveal that acute application of NMDA
      increases miniature IPSC (mIPSC) frequency. Interestingly, after 2 weeks, the
      mIPSC frequency increases compared with the first week but is not modulated by
      NMDA. Furthermore, in cultures chronically treated with NMDA for 1 week, the size
      of the GABAergic boutons increases. This growth is paralleled by increased mIPSC
      frequency and the loss of NMDA sensitivity. Direct patch-clamp recording from
      these presynaptic terminals reveals single NMDA-activated channels, showing
      multiple conductance levels, and electronic propagation from the somatodendritic
      compartment. Our results demonstrate that NMDA receptors alter GABAergic synapses
      in developing cerebellar cultures by increasing the size of the terminal and
      spontaneous GABA release. These findings parallel changes in inhibitory synaptic
      efficacy seen in vivo in developing GABAergic interneurons of the molecular layer
      of the cerebellum.

PMID- 15728843
TI  - Medial septal GABAergic neurons express the somatostatin sst2A receptor:
      functional consequences on unit firing and hippocampal theta.
AB  - GABAergic septohippocampal neurons play a major role in the generation of
      hippocampal theta rhythm, but modulatory factors intervening in this function are
      poorly documented. The neuropeptide somatostatin (SST) may be one of these
      factors, because nearly all hippocampal GABAergic neurons projecting to the
      medial septum/diagonal band of Broca (MS-DB) express SST. In this study, we took
      advantage of the high and selective expression of the SST receptor sst2A in MS-DB
      to examine its possible role on theta-related activity. Immunohistochemical
      experiments demonstrated that sst2A receptors were selectively targeted to the
      somatodendritic domain of neurons expressing the GABAergic marker GAD67 but were
      not expressed by cholinergic neurons. In addition, a subpopulation of GABAergic
      septohippocampal projecting neurons expressing parvalbumin (PV) also displayed
      sst2A receptors. Using in vivo juxtacellular recording and labeling with
      neurobiotin, we showed that a number of bursting and nonbursting neurons
      exhibiting high discharge rates and brief spikes were immunoreactive for PV or
      GAD67 and expressed the sst2A receptor. Microiontophoresis applications of SST
      and the sst2A agonist octreotide (OCT) showed that sst2A receptor activation
      decreased the discharge rate of both nonbursting and bursting MS-DB neurons and
      lessened the rhythmic activity of the latter. Finally, intraseptal injections of
      OCT and SST in freely moving rats reduced the power of hippocampal EEG in the
      theta band. Together, these in vivo experiments suggest that SST action on MS-DB
      GABAergic neurons, through sst2A receptors, represents an important modulatory
      mechanism in the control of theta activity.

PMID- 15728844
TI  - Calcium-independent, cGMP-mediated light adaptation in invertebrate ciliary
      photoreceptors.
AB  - Calcium is thought to be essential for adaptation of sensory receptor cells.
      However, the transduction cascade of hyperpolarizing, ciliary photoreceptors of
      the scallop does not use IP3-mediated Ca release, and the light-sensitive
      conductance is not measurably permeable to Ca2+. Therefore, two typical
      mechanisms that couple the light response to [Ca]i changes seem to be lacking in
      these photoreceptors. Using fluorescent indicators, we determined that, unlike in
      their microvillar counterparts, photostimulation of ciliary cells under voltage
      clamp indeed evokes no detectable change in cytosolic Ca. Notwithstanding, these
      cells exhibit all of the hallmarks of light adaptation, including response range
      compression, sensitivity shift, and photoresponse acceleration. A possible
      mediator of Ca-independent sensory adaptation is cGMP, the second messenger that
      regulates the light-sensitive conductance; cGMP and 8-bromo cGMP not only
      activate light-dependent K channels but also reduce the amplitude of the light
      response to an extent greatly in excess of that expected from simple occlusion
      between light and chemical stimulation. In addition, these substances accelerate
      the time course of the photocurrent. Tests with pharmacological antagonists
      suggest that protein kinase G may be a downstream effector that controls, in
      part, the cGMP-triggered changes in photoresponse properties during light
      adaptation. However, additional messengers are likely to be implicated,
      especially in the regulation of response kinetics. These observations suggest a
      novel feedback inhibition pathway for signaling sensory adaptation.

PMID- 15728845
TI  - Role for Runx1 in the proliferation and neuronal differentiation of selected
      progenitor cells in the mammalian nervous system.
AB  - Neurogenesis requires factors that regulate the decision of dividing progenitors
      to leave the cell cycle and activate the neuronal differentiation program. It is
      shown here that the murine runt-related gene Runx1 is expressed in proliferating
      cells on the basal side of the olfactory epithelium. These include both Mash1+
      olfactory receptor neuron (ORN) progenitors and NeuroD+ ORN precursors.
      Disruption of Runx1 function in vivo does not cause a change in Mash1 expression
      but leads to a decrease in the number of NeuroD+ neuronal precursors and an
      increase in differentiated ORNs. These effects result in premature and ectopic
      ORN differentiation. It is shown further that exogenous Runx1 expression in
      cultured olfactory neural progenitors causes an expansion of the mitotic cell
      population. In agreement with these findings, exogenous Runx1 expression also
      promotes cortical neural progenitor cell proliferation without inhibiting
      neuronal differentiation. These effects are phenocopied by a chimeric protein
      containing ETO, the eight twenty one transcriptional repressor, fused to the
      Runx1 DNA-binding domain, which suggests the involvement of transcription
      repression mechanisms. Consistent with this possibility, Runx1 represses
      transcription driven by the promoter of the cell cycle inhibitor p21Cip 1 in
      cortical progenitors. Together, these findings suggest a previously unrecognized
      role for Runx1 in coordinating the proliferation and neuronal differentiation of
      selected populations of neural progenitors.

PMID- 15728846
TI  - Theta stimulation polymerizes actin in dendritic spines of hippocampus.
AB  - It has been proposed that the endurance of long-term potentiation (LTP) depends
      on structural changes entailing reorganization of the spine actin cytoskeleton.
      The present study used a new technique involving intracellular and extracellular
      application of rhodamine-phalloidin to conventional hippocampal slices to test
      whether induction of LTP by naturalistic patterns of afferent activity
      selectively increases actin polymerization in juvenile to young adult spines.
      Rhodamine-phalloidin, which selectively binds to polymerized actin, was detected
      in perikarya and proximal dendrites of CA1 pyramidal cells that received low
      frequency afferent activity but was essentially absent in spines and fine
      dendritic processes. Theta pattern stimulation induced LTP and caused a large
      (threefold), reliable increase in labeled spines and spine-like puncta in the
      proximal dendritic zone containing potentiated synapses. The spines frequently
      occurred in the absence of labeling to other structures but were also found in
      association with fluorescent dendritic processes. These effects were replicated
      (>10-fold increase in labeled spines) using extracellular applications of
      rhodamine-phalloidin. Increases in labeling appeared within 2 min, were
      completely blocked by treatments that prevent LTP induction, and occurred in
      slices prepared from young adult rats. These results indicate that near-threshold
      conditions for inducing stable potentiation cause the rapid polymerization of
      actin in mature spines and suggest that the effect is both sufficiently discrete
      to satisfy the synapse-specificity rule of LTP as well as rapid enough to
      participate in the initial stages of LTP consolidation.

PMID- 15728847
TI  - Acquisition, consolidation, reconsolidation, and extinction of eyelid
      conditioning responses require de novo protein synthesis.
AB  - Memory, as measured by changes in an animal's behavior some time after learning,
      is a reflection of many processes. Here, using a trace paradigm, in mice we show
      that de novo protein synthesis is required for acquisition, consolidation,
      reconsolidation, and extinction of classically conditioned eyelid responses. Two
      critical periods of protein synthesis have been found: the first, during
      training, the blocking of which impaired acquisition; and the second, lasting the
      first 4 h after training, the blocking of which impaired consolidation. The
      process of reconsolidation was sensitive to protein synthesis inhibition if
      anisomycin was injected before or just after the reactivation session.
      Furthermore, extinction was also dependent on protein synthesis, following the
      same temporal course as that followed during acquisition and consolidation. This
      last fact reinforces the idea that extinction is an active learning process
      rather than a passive event of forgetting. Together, these findings demonstrate
      that all of the different stages of memory formation involved in the classical
      conditioning of eyelid responses are dependent on protein synthesis.

PMID- 15728848
TI  - Polysialylated neural cell adhesion molecule is necessary for selective targeting
      of regenerating motor neurons.
AB  - It is well established that peripheral nerves regenerate after injury. Therefore,
      incomplete functional recovery usually results from misguided axons rather than a
      lack of regeneration per se. Despite this knowledge very little is known about
      the molecular mechanisms regulating axon guidance during regeneration. In the
      developing neuromuscular system the neural cell adhesion molecule (NCAM) and its
      polysialic acid (PSA) moiety are essential for proper motor axon guidance. In
      this study we used a well established model of nerve transection and repair to
      examine whether NCAM and/or PSA promotes selective regeneration of femoral motor
      nerves in wild-type and NCAM (-/-) mice. We found that regenerating axons
      innervating the muscle pathway and, to a lesser extent, cutaneous axons in the
      sensory pathway reexpress high levels of PSA during the time when the cut axons
      are crossing the lesion site. Second, we found that motor neurons in wild-type
      mice preferentially reinnervated muscle pathways, whereas motor neurons in NCAM (
      /-) mice reinnervated muscle and cutaneous pathways with equal preference.
      Preferential regeneration was not observed in wild-type mice when PSA was removed
      enzymatically from the regenerating nerve, indicating that this form of selective
      motor axon targeting requires PSA. Finally, transgenic mice were used to show
      that the number of collateral sprouts, their field of arborization, and the
      withdrawal of misprojected axons were all attenuated significantly in mice
      lacking PSA. These results indicate that regenerating motor axons must express
      polysialylated NCAM, which reduces axon-axon adhesion and enables motor neurons
      to reinnervate their appropriate muscle targets selectively.

PMID- 15728849
TI  - Rhythmic bursting in the cortico-subthalamo-pallidal network during spontaneous
      genetically determined spike and wave discharges.
AB  - Absence seizures are characterized by impairment of consciousness associated with
      bilaterally synchronous spike-and-wave discharges (SWDs) in the
      electroencephalogram (EEG), which reflect paroxysmal oscillations in
      thalamocortical networks. Although recent studies suggest that the subthalamic
      nucleus (STN) provides an endogenous control system that influences the
      occurrence of absence seizures, the mechanisms of propagation of cortical
      epileptic discharges in the STN have never been explored. The present study
      provides the first description of the electrophysiological activity in the
      cortico-subthalamo-pallidal network during absence seizures in the genetic
      absence epilepsy rats from Strasbourg, a well established model of absence
      epilepsy. In corticosubthalamic neurons, the SWDs were associated with repetitive
      suprathreshold depolarizations correlated with EEG spikes. These cortical
      paroxysms were reflected in the STN by synchronized, rhythmic, high-frequency
      bursts of action potentials. Intracellular recordings revealed that the
      intraburst pattern in STN neurons was sculpted by an early depolarizing synaptic
      potential, followed by a short hyperpolarization and a rebound of excitation. The
      rhythmic hyperpolarizations in STN neurons during SWDs likely originate from a
      subpopulation of pallidal neurons exhibiting rhythmic bursting temporally
      correlated with the EEG spikes. The repetitive discharges in STN neurons
      accompanying absence seizures might convey powerful excitation to basal ganglia
      output nuclei and, consequently, may participate in the control of
      thalamocortical SWDs.

PMID- 15728850
TI  - Involvement of sensorimotor, limbic, and associative basal ganglia domains in L
      3,4-dihydroxyphenylalanine-induced dyskinesia.
AB  - Dyskinesia represents a debilitating complication of L-3,4-dihydroxyphenylalanine
      (L-dopa) therapy for Parkinson's disease. Such motor manifestations are
      attributed to pathological activity in the motor parts of basal ganglia. However,
      because consistent funneling of information takes place between the sensorimotor,
      limbic, and associative basal ganglia domains, we hypothesized that nonmotor
      domains play a role in these manifestations. Here we report the changes in 2
      deoxyglucose (2-DG) accumulation in the sensorimotor, limbic, and associative
      domains of basal ganglia and thalamic nuclei of four groups of nonhuman primates:
      normal, parkinsonian, parkinsonian chronically treated with L-dopa without
      exhibiting dyskinesia, and parkinsonian chronically treated with L-dopa and
      exhibiting overt dyskinesia. Although nondyskinetic animals display a rather
      normalized metabolic activity, dyskinetic animals are distinguished by
      significant changes in 2-DG accumulation in limbic- and associative-related
      structures and not simply in sensorimotor-related ones, suggesting that
      dyskinesia is linked to a pathological processing of limbic and cognitive
      information. We propose that these metabolic changes reflect the underlying
      neural mechanisms of not simply motor dyskinesias but also affective,
      motivational, and cognitive disorders associated with long-term exposure to L
      dopa.

PMID- 15728851
TI  - Metabotropic P2Y purinoceptor-mediated presynaptic and postsynaptic enhancement
      of cerebellar GABAergic transmission.
AB  - Cerebellar GABAergic inhibitory transmission is under heterosynaptic control
      mediated by diverse chemical messengers. Here, we investigated roles of
      metabotropic P2Y purinoceptors (P2YRs) on GABAergic synapses between cerebellar
      interneurons and Purkinje cells (PCs). Activation of P2Y purinoceptors by two
      selective agonists, ADP and 2-methylthio-ADP (2MeSADP), elicited two distinct
      forms of synaptic plasticity of GABAergic transmission in the cerebellar cortex.
      First, the two agonists induced long-lasting enhancement of stimulation-evoked
      GABAergic IPSCs as well as GABA(A) receptor currents in PCs. This effect was
      completely abolished by intracellular infusion of the Ca2+-chelating agent BAPTA.
      Measurements of intracellular Ca2+ ([Ca2+]i) dynamics showed that puff
      application of 2MeSADP produced an increase in [Ca2+]i of PCs and that this
      increase persisted in an external Ca2+-deficient medium. These results suggest
      that P2Y activation postsynaptically elicits long-term enhancement of GABA(A)
      receptor sensitivity of PCs through a Gq-mediated increase in [Ca2+]i. The other
      action of P2YR agonists on cerebellar GABAergic synapses was that they produced a
      short-term increase in the frequency and the amplitude of spontaneous GABAA
      receptor-mediated IPSCs in PCs in a manner sensitive to a P2Y1R antagonist, N6
      methyl 2'-deoxyadenosine 3',5'-bisphosphate. This action appeared to be
      attributable to an excitability increase in presynaptic GABAergic interneurons,
      because ADP excited all Lugaro cells examined and some of interneurons in the
      molecular layer. These results suggest that activation of cerebellar P2Y
      purinoceptors leads to modulation of GABAergic transmission in different spatial
      and temporal domains, namely short-term and long-term plasticity through
      presynaptic and postsynaptic mechanisms at interneuron-->PC inhibitory synapses
      in the rat cerebellar cortex.

PMID- 15728852
TI  - Retinotopic axis specificity and selective clustering of feedback projections
      from V2 to V1 in the owl monkey.
AB  - Cortical maps and feedback connections are ubiquitous features of the visual
      cerebral cortex. The role of the feedback connections, however, is unclear. This
      study was aimed at revealing possible organizational relationships between the
      feedback projections from area V2 and the functional maps of orientation and
      retinotopy in area V1. Optical imaging of intrinsic signals was combined with
      cytochrome oxidase histochemistry and connectional anatomy in owl monkeys. Tracer
      injections were administered at orientation-selective domains in regions of pale
      and thick cytochrome oxidase stripes adjacent to the border between these
      stripes. The feedback projections from V2 were found to be more diffuse than the
      intrinsic horizontal connections within V1, but they nevertheless demonstrated
      clustering. The clusters of feedback axons projected preferentially to interblob
      cytochrome oxidase regions. The distribution of preferred orientations of the
      recipient domains in V1 was broad but appeared biased toward values similar to
      the preferred orientation of the projecting cells in V2. The global spatial
      distribution of the feedback projections in V1 was anisotropic. The major axis of
      anisotropy was systematically parallel to a retinotopic axis in V1 corresponding
      to the preferred orientation of the cells of origin in V2. We conclude that the
      feedback connections from V2 to V1 might play a role in enhancing the response in
      V1 to collinear contour elements.

PMID- 15728853
TI  - 3,4-dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient aphakia
      mice: behavioral characterization of a novel genetic model of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss
      of dopaminergic neurons in the substantia nigra. There is a need for genetic
      animal models of PD for screening and in vivo testing of novel restorative
      therapeutic agents. Although current genetic models of PD produce behavioral
      impairment and nigrostriatal dysfunction, they do not reproduce the loss of
      midbrain dopaminergic neurons and 3,4-dihydroxyphenylalanine (L-DOPA) reversible
      behavioral deficits. Here, we demonstrate that Pitx3-deficient aphakia (ak) mice,
      which have been shown previously to exhibit a major loss of substantia nigra
      dopaminergic neurons, display motor deficits that are reversed by L-DOPA and
      evidence of "dopaminergic supersensitivity" in the striatum. Thus, ak mice
      represent a novel genetic model exhibiting useful characteristics to test the
      efficacy of symptomatic therapies for PD and to study the functional changes in
      the striatum after dopamine depletion and L-DOPA treatment.

PMID- 15728854
TI  - Impaired synaptic plasticity and learning in mice lacking beta-adducin, an actin
      regulating protein.
AB  - The adducin family of proteins interacts with the actin cytoskeleton and the
      plasma membrane in a calcium- and cAMP-dependent manner. Thus, adducins may be
      involved in changes in cytoskeletal organization resulting from synaptic
      stimulation. beta-Adducin knock-out mice were examined in physiological and
      behavioral paradigms related to synaptic plasticity to elucidate the role the
      adducin family plays in processes underlying learning and memory. In situ
      hybridization for alpha- and beta-adducin demonstrates that these mRNAs are found
      throughout the brain, with high levels of expression in the hippocampus. Schaffer
      collateral-CA1 tetanic long-term potentiation decayed rapidly in acute
      hippocampal slices from beta-adducin knock-out mice, although baseline spine
      morphology and postsynaptic density were normal. Interestingly, the input-output
      relationship was significantly increased in hippocampal slices from beta-adducin
      knock-out mice. Furthermore, beta-adducin knock-out mice were impaired in
      performance of fear conditioning and the water maze paradigm. The current results
      indicate that beta-adducin may play an important role in the cellular mechanisms
      underlying activity-dependent synaptic plasticity associated with learning and
      memory.

PMID- 15728855
TI  - Control of synaptic connection by glutamate receptor delta2 in the adult
      cerebellum.
AB  - Precise topological matching of presynaptic and postsynaptic specializations is
      essential for efficient synaptic transmission. Furthermore, synaptic connections
      are subjected to rearrangements throughout life. Here we examined the role of
      glutamate receptor (GluR) delta2 in the adult brain by inducible and cerebellar
      Purkinje cell (PC)-specific gene targeting under the pure C57BL/6 genetic
      background. Concomitant with the decrease of postsynaptic GluRdelta2 proteins,
      presynaptic active zones shrank progressively and postsynaptic density (PSD)
      expanded, resulting in mismatching between presynaptic and postsynaptic
      specializations at parallel fiber-PC synapses. Furthermore, GluRdelta2 and PSD-93
      proteins were concentrated at the contacted portion of mismatched synapses,
      whereas AMPA receptors were distributed in both the contacted and dissociated
      portions. When GluRdelta2 proteins were diminished, PC spines lost their synaptic
      contacts. We thus identified postsynaptic GluRdelta2 as a key regulator of the
      presynaptic active zone and PSD organization at parallel fiber-PC synapses in the
      adult brain.

PMID- 15728857
TI  - Whither onchocerciasis control in Africa?

PMID- 15728858
TI  - New concepts in the diagnosis and management of neurocysticercosis (Taenia
      solium).
AB  - Human neurocysticercosis, the infection of the nervous system by the larvae of
      Taenia solium, is a major cause of epileptic seizures and other neurologic
      morbidity worldwide. The diagnosis and treatment of neurocysticercosis have been
      considerably improved in recent years. This improvement includes identification
      and sequencing of specific antigens and development of new assays for laboratory
      diagnosis, recognition of the frequency and significance of edema around old,
      calcified cysts (associated to symptomatic episodes), results of a randomized
      blinded control treatment trial on treatment efficacy for intraparenchymal
      disease showing a clinical benefit of decreased seizures, and a much better
      assessment of the frequency and spectrum of cerebrovascular complications. These
      advances now permit a much better integration of clinical, serologic, and imaging
      data for diagnosis and therapeutic purposes.

PMID- 15728856
TI  - D2 dopamine receptors colocalize regulator of G-protein signaling 9-2 (RGS9-2)
      via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated
      with dopamine pathways.
AB  - Regulator of G-protein signaling 9-2 (RGS9-2), a member of the RGS family of G
      GTPase accelerating proteins, is expressed specifically in the striatum, which
      participates in antipsychotic-induced tardive dyskinesia and in levodopa-induced
      dyskinesia. We report that RGS9 knock-out mice develop abnormal involuntary
      movements when inhibition of dopaminergic transmission is followed by activation
      of D2-like dopamine receptors (DRs). These abnormal movements resemble drug
      induced dyskinesia more closely than other rodent models. Recordings from
      striatal neurons of these mice establish that activation of D2-like DRs
      abnormally inhibits glutamate-elicited currents. We show that RGS9-2, via its DEP
      domain (for Disheveled, EGL-10, Pleckstrin homology), colocalizes with D2DRs when
      coexpressed in mammalian cells. Recordings from oocytes coexpressing D2DR or the
      m2 muscarinic receptor and G-protein-gated inward rectifier potassium channels
      show that RGS9-2, via its DEP domain, preferentially accelerates the termination
      of D2DR signals. Thus, alterations in RGS9-2 may be a key factor in the pathway
      leading from D2DRs to the side effects associated with the treatment both of
      psychoses and Parkinson's disease.

PMID- 15728859
TI  - Short report: prospective evaluation of a multi-test strip for the diagnoses of
      scrub and murine typhus, leptospirosis, dengue Fever, and Salmonella typhi
      infection.
AB  - A multi-test strip dotblot immunoassay for the diagnosis of typhoid fever, scrub
      typhus, murine typhus, dengue virus infection and leptospirosis was evaluated in
      Thai adults presenting to hospital with acute, undifferentiated fever. The kit
      gave multiple positive test results in 33 of 36 patients with defined infections
      and was therefore not a useful admission diagnostic tool.

PMID- 15728860
TI  - Experimental leptospirosis in marmoset monkeys (Callithrix jacchus): a new model
      for studies of severe pulmonary leptospirosis.
AB  - Experimental infection of marmoset monkeys (Callithrix jacchus) with Leptospira
      interrogans serovar Copenhageni showed microscopic patterns of tissue reactions
      comparable to those seen in the severe forms of human leptospirosis, including
      intra-alveolar hemorrhage. The most impressive microscopic changes were seen in
      the lung and kidney of animals killed at days 6 and 12 after inoculation. There
      were extensive and irregular areas of hemorrhage predominating around main
      bronchial branches or diffusely spread to the pulmonary parenchyma, as well as
      severe tubulointerstitial nephritis. Antibody response detected by the
      microscopic agglutination test was quantitatively similar to those seen in humans
      and paralleled severity of tissue lesions. The distribution of leptospires or
      antigenic debris in infected tissues was observed by immunofluorescence and
      confocal laser scanning microscopy. Large numbers of typical leptospires were
      seen in the lumen of proximal renal tubules. Positive reactions showing antigenic
      debris were closely associated with sites of tissue damage.

PMID- 15728861
TI  - Do African immigrants living in France have long-term malarial immunity?
AB  - Among populations living in areas endemic for malaria, repeated parasite exposure
      leads to a gradual increase in protective immunity to the disease. In contrast,
      this immunity is assumed to disappear after several years of non-exposure. This
      study was designed to investigate long-term immunity in subjects removed from the
      risk of exposure. Plasmodium falciparum malaria attacks occurring after short
      trips to sub-Saharan Africa were compared between 99 European patients and 252
      African immigrants who had been resident in Europe for at least four years.
      Relative to the European patients, those originating from Africa had lower mean
      +/- SD parasite densities (0.8 +/- 1.5/100 red blood cells versus 1.4 +/- 2.8/100
      red blood cells; P = 0.007), less frequent severe disease (4.4% versus 15.2%; P =
      0.0005), accelerated parasite clearance and defervescence, and higher levels of
      antibodies to P. falciparum. These results suggest the persistence of acquired
      immunity to P. falciparum malaria after several years of non-exposure in African
      immigrants.

PMID- 15728862
TI  - Usefulness of a rapid on-site Plasmodium falciparum diagnosis (Paracheck PF) in
      forest migrants and among the indigenous population at the site of their
      occupational activities in central India.
AB  - Logistic, economic, and technical factors limit rapid access to microscopic
      confirmation of malaria in many tropical countries, including India. The
      occurrence of high-grade fever and three deaths during the hot summer months in
      some forest migrants created an emergency situation in Jabalpur in central India.
      A cheap and rapid malaria test, Paracheck Pf, was tested in this group of
      migrants in parallel with microscopy. The indigenous population at the site of
      occupational activities of these migrants approximately 250 km from Jabalpur was
      also screened by both methods. The results of this field investigation are very
      encouraging. Among migrants, the test had a sensitivity of 100% and a specificity
      of 67%. The positive and negative predictive values were 94% and 100%,
      respectively. Among indigenous population, the corresponding values were 100%,
      97.3%, 98.4%, and 100%, respectively, indicating the usefulness of test as a
      diagnostic tool for providing on-site confirmation of symptomatic diagnosis of
      Plasmodium falciparum malaria.

PMID- 15728863
TI  - Nexus of infection with human immunodeficiency virus, pulmonary tuberculosis and
      visceral leishmaniasis: a case report from Bihar, India.
AB  - A 37-year-old man was diagnosed as being infected with human immunodeficiency
      virus (HIV), tuberculosis (TB), tuberculoma of the brain, and visceral
      leishmaniasis (VL) at the Rajendra Memorial Institute of Medical Sciences in
      Bihar, India. He had taken anti-tuberculosis therapy (ATT) for two and a half
      months and had episodes of convulsions with loss of consciousness, tongue bites,
      and incontinence of urine. The results of a neurologic examination were normal
      except for a left plantar extensor. He was positive for both HIV-I (confirmed by
      Western blot) and VL (confirmed by splenic aspirate). Treatment was initiated
      with amphotericin B lipid complex, a four-drug regimen (rifampicin, isoniazid,
      ethambutol, and pyrazinamide) of ATT, highly active antiretroviral therapy, anti
      convulsants, and other supportive therapies. A repeat computed tomography scan of
      the brain showed the disappearance of the lesion followed by gliosis. After six
      months, he was also cured of VL. The triad of infections (HIV, VL, and TB) is a
      real threat in Bihar as an emerging combination of diseases of public health
      importance. Keeping these facts in mind, efforts to develop simple and cost
      effective diagnostic techniques coupled with affordable therapeutic facilities
      are urgently needed in developing countries.

PMID- 15728864
TI  - Infection with human immunodeficiency virus, herpes simplex virus type 2, and
      human herpes virus 8 in remote villages of southwestern Papua New Guinea.
AB  - To investigate the spread of human immunodeficiency virus (HIV) and other
      sexually transmitted viruses, two serosurveys (the first in 1999 among 56 adults
      and the second in 2001 among 351 adults) were conducted in remote villages of the
      southwestern part of Papua New Guinea. Only one individual was positive for
      antibodies to HIV. In 2001, the seroprevalence of human herpes virus 8 (HHV-8)
      was 32.2%, and the seroprevalence of herpes simplex virus type 2 (HSV-2) was
      27.4%. Both prevalence rates increased with age, and were lower in the villages
      near the Bensbach River. The seropositivity of HSV-2 was independently correlated
      with HHV-8 infection. Our data show that the inhabitants of the southwestern
      region of Papua New Guinea currently experience an extremely low circulation of
      HIV. However, the high prevalence of infectious agents that can be sexually
      transmitted, such as HSV-2 and to a lesser extent HHV-8, indicates the presence
      of behavioral patterns that may facilitate the spread of HIV in this area of
      currently low endemicity.

PMID- 15728865
TI  - Seroprevalence of infection with Toxoplasma gondii in indigenous Brazilian
      populations.
AB  - The prevalence of Toxoplasma gondii in indigenous Brazilian tribes with different
      degrees of acculturation was studied in the Enawene-Nawe, an isolated tribe, in
      the state of Mato Grosso, the Waiapi, with intermittent non-Indian contacts, in
      the state of Amapa, and the Tiriyo, with constant non-Indian contacts, in the
      state of Para. An IgG-enzyme-linked immunosorbent assay (IgG-ELISA) or an IgG/IgM
      indirect immunofluorescence antibody (IFA) assay were performed for the detection
      of antibodies to T. gondii in 2000-2001. Both assays showed that the Tiriyo had
      the lowest crude seroprevalence (55.6%), the Enawene-Nawe the highest crude
      seroprevalence (80.4%), and the Waiapi an intermediate crude seroprevalence
      (59.6%). The age-adjusted prevalence (95% confidence intervals) values for the
      Tiriyo, Enawene-Nawe, and Waiapi were 57.3% (53.4, 61.1%), 78.8% (72.2, 85.7%),
      and 57.7% (52.5, 62.9%), respectively. Contact with non-Indians probably did not
      influence the prevalence of the infection. However, differential contact with
      soil-harboring oocysts from wild felines may be responsible for the various
      seroprevalences in the different tribes.

PMID- 15728866
TI  - Hantavirus pulmonary syndrome in Central Bolivia: relationships between reservoir
      hosts, habitats, and viral genotypes.
AB  - In August 2002, two cases of hantavirus pulmonary syndrome (HPS) were confirmed
      in Mineros and Concepcion, within the Santa Cruz Department of Bolivia. Extensive
      alteration of the native ecosystem, from dense forest to pasture or sugarcane,
      had occurred in both regions. An ecologic assessment of reservoir species
      associated with the human disease identified a single hantavirus antibody
      positive Oligoryzomys microtis from Mineros and three hantavirus antibody
      positive Calomys callosus from Concepcion. In Mineros, the virus from the O.
      microtis was 90% similar to sequences published for Rio Mamore virus. Viral
      nucleotide sequences from two C. callosus were 87-88% similar to the sequence of
      Laguna Negra virus. The viral sequence from the C. callosus was 99% identical to
      viral sequences obtained from the HPS patient in this area, implicating C.
      callosus as the host and Laguna Negra virus as the agent responsible for the HPS
      case near Concepcion.

PMID- 15728867
TI  - Factors associated with hemoglobin concentrations in pre-school children in
      Western Kenya: cross-sectional studies.
AB  - In sub-Saharan Africa, the etiology of anemia in early childhood is complex and
      multifactorial. Three community-based cross-sectional surveys were used to
      determine the prevalence and severity of anemia. Regression methods were used to
      compare mean hemoglobin (Hb) concentrations across covariate levels to identify
      children at risk of low Hb levels in an area with intense malaria transmission.
      In a random sample of 2,774 children < 36 months old, the prevalence of anemia
      (Hb < 11g/dL) was 76.1% and 71%, respectively, in villages without and with
      insecticide-treated bed nets (ITNs); severe-moderate anemia (Hb < 7 g/dL) was
      observed in 11% (non-ITN) and 8.3% (ITN). The prevalence of anemia, high-density
      malaria parasitemia (21.7%), microcytosis (34.9%), underweight (21.9%), and
      diarrhea (54.8%) increased rapidly from age three months onwards and remained
      high until 35 months of age. Multivariate analyses showed that family size,
      history of fever, pale body, general body weakness, diarrhea, soil-eating,
      concurrent fever, stunting, and malaria parasitemia were associated with mean Hb
      levels. Prevention of severe anemia should start early in infancy and include a
      combination of micronutrient supplementation, malaria control, and possibly
      interventions against diarrheal illness.

PMID- 15728868
TI  - Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living
      in Bandung, West Java, Indonesia.
AB  - A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was
      conducted in a cohort of adult volunteers from two textile factories located in
      West Java, Indonesia. Volunteers in the cohort were bled every three months and
      were actively followed for the occurrence of dengue (DEN) disease. The first two
      years of the study showed an incidence of symptomatic DEN disease of 18 cases per
      1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases
      per 1,000 person-years in areas of high disease transmission. In areas where no
      symptomatic cases were detected, the incidence of asymptomatic or mild infection
      was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype
      identified, but all four serotypes were detected among the cohort. Four cases of
      DHF and one case of dengue shock syndrome (DSS) were identified. Three of the
      four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting
      of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1
      virus. To our knowledge, this is the first report of a longitudinal cohort study
      of naturally acquired DF and DHF in adults.

PMID- 15728869
TI  - Elimination of dengue by community programs using Mesocyclops(Copepoda) against
      Aedes aegypti in central Vietnam.
AB  - From September 2000 to June 2003, a community-based program for dengue control
      using local predacious copepods of the genus Mesocyclops was conducted in three
      rural communes in the central Vietnam provinces of Quang Nam, Quang Ngai, and
      Khanh Hoa. Post-project, three subsequent entomologic surveys were conducted
      until March 2004. The number of households and residents in the communes were
      5,913 and 27,167, respectively, and dengue notification rates for these communes
      from 1996 were as high as 2,418.5 per 100,000 persons. Following knowledge,
      attitude, and practice evaluations, surveys of water storage containers indicated
      that Mesocyclops spp. already occurred in 3-17% and that large tanks up to 2,000
      liters, 130-300-liter jars, wells, and some 220-liter metal drums were the most
      productive habitats for Aedes aegypti. With technical support, the programs were
      driven by communal management committees, health collaborators, schoolteachers,
      and pupils. From quantitative estimates of the standing crop of third and fourth
      instars from 100 households, Ae. aegypti were reduced by approximately 90% by
      year 1, 92.3-98.6% by year 2, and Ae. aegypti immature forms had been eliminated
      from two of three communes by June 2003. Similarly, from resting adult
      collections from 100 households, densities were reduced to 0-1 per commune. By
      March 2004, two communes with no larvae had small numbers but the third was
      negative; one adult was collected in each of two communes while one became
      negative. Absolute estimates of third and fourth instars at the three
      intervention communes and one left untreated had significant correlations (P =
      0.009-< 0.001) with numbers of adults aspirated from inside houses on each of 15
      survey periods. By year 1, the incidence of dengue disease in the treated
      communes was reduced by 76.7% compared with non-intervention communes within the
      same districts, and no dengue was evident in 2002 and 2003, compared with 112.8
      and 14.4 cases per 100,000 at district level. Since we had similar success in
      northern Vietnam from 1998 to 2000, this study demonstrates that this control
      model is broadly acceptable and achievable at community level but vigilance is
      required post-project to prevent reinfestation.

PMID- 15728870
TI  - Replication of chimeric yellow fever virus-dengue serotype 1-4 virus vaccine
      strains in dendritic and hepatic cells.
AB  - ChimeriVax-dengue (DEN) viruses are live attenuated vaccine candidates. They are
      constructed by replacing the premembrane (prM) and envelope (E) genes of the
      yellow fever (YF) 17D virus vaccine with the corresponding genes from wild-type
      DEN viruses (serotypes 1-4) isolated from humans. In this study, the growth
      kinetics of ChimeriVax-DEN1-4 and parent viruses (wild-type DEN-1-4 and YF 17D)
      were assessed in human myeloid dendritic cells (DCs) and in three hepatic cell
      lines (HepG2, Huh7, and THLE-3). In DC, ChimeriVax-DEN-1-4 showed similar growth
      kinetics to their parent viruses, wild-type DEN virus (propagated in Vero cells),
      or YF 17D virus (peak titers ~3-4.5 log(10) plaque-forming units (PFU)/mL at 48
      72 hours post-infection). Parent wild-type DEN-1-4 viruses derived from C6/36
      mosquito cells did not show any growth at a multiplicity of infection of 0.1 in
      DCs, except for DEN-2 virus, which grew to a modest titer of 2.5 log(10) PFU/mL
      at 48 hours post-infection. ChimeriVax-DEN1-4 grew to significantly lower titers
      (2-5 log(10) PFU/mL) than YF 17D virus in hepatic cell lines THLE-3 and HepG2,
      but not in Huh7 cells. These experiments suggest that ChimeriVax-DEN1-4 viruses
      replicate similarly to YF-VAX in DCs, but at a lower level than YF 17D virus in
      hepatic cell lines. The lack of growth of chimeric viruses in human hepatic cells
      suggests that these viruses may be less hepatotropic than YF 17D virus vaccine in
      humans.

PMID- 15728871
TI  - Serodiagnosis of human fascioliasis by a cystatin capture enzyme-linked
      immunosorbent assay with recombinant Fasciola gigantica cathepsin L antigen.
AB  - Cathepsin L1, a cysteine protease secreted by the gastrodermis of juvenile and
      adult Fasciola gigantica, was expressed in Escherichia coli as a calmodulin
      binding peptide fusion protein with a molecular mass of approximately 35 kD. The
      recombinant cathepsin L1 (rCTL1) was tested for its antigenic potential in a
      cystatin capture enzyme-linked immunosorbent assay (ELISA) to diagnose human
      fascioliasis. The ELISA plates were sensitized with chicken egg cystatin and
      incubated with bacterial lysates containing the recombinant protein before the
      standard ELISA procedures were performed. Analysis of the sera of 13 patients
      infected with F. gigantica (group 1), 204 patients with other parasitic
      infections (group 2), 32 cholangiocarcinoma patients (group 3), and 42 healthy
      controls (group 4) showed that the sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of this ELISA using rCTL1 were
      100%, 98.92%, 98.97%, 81.25%, and 100%, respectively. These results indicate that
      this assay has high sensitivity and specificity in the diagnosis of human
      fascioliasis. In addition, we have produced sufficient amounts of antigen for use
      in diagnosis.

PMID- 15728872
TI  - Detection and identification of Leishmania species within naturally infected sand
      flies in the andean areas of ecuador by a polymerase chain reaction.
AB  - The surveillance of prevalent Leishmania and sand fly species in endemic areas is
      important for prediction of the risk and expansion of leishmaniasis. In this
      study, we developed a polymerase chain reaction (PCR)-based method for detection
      of Leishmania minicircle DNA within individual sand flies. Using this method, we
      detected minicircle DNA in 6 (3.3%) of 183 sand flies, while 5 (3.5%) of 143 were
      positive for Leishmania promastigotes in the same areas by microscopic
      examination. The species were identified as Leishmania (Leishmania) mexicana by
      nucleotide sequencing of the cytochrome b gene. Additionally, all the Leishmania
      positive sand flies were identified as Lutzomyia ayacuchensis by the restriction
      enzyme digestion of the PCR-amplified 18S ribosomal RNA gene fragments. Since
      this combined method is relatively easy and can process a large number of
      samples, it will be a powerful tool for the rapid identification of prevalent
      sand fly and Leishmania species as well as monitoring the infection rate in sand
      fly populations in endemic areas.

PMID- 15728873
TI  - Inflammatory cell infiltration and high antibody production in BALB/c mice caused
      by natural exposure to Lutzomyia longipalpis bites.
AB  - Sand flies inject saliva into the mammalian host when probing for a blood meal.
      Understanding the initial vertebrate reactions against sand fly saliva is
      important for possible interventions because these insects transmit diseases to
      humans and other animals. Little is known of these reactions to New World sand
      flies. Repeated exposure of BALB/c mice to Lutzomyia longipalpis bites leads to
      local inflammatory cell infiltration comprised of neutrophils, macrophages, and
      eosinophils. Total IgG and IgG1 antibodies react predominantly with three major
      protein bands (45, 44, and 16 kD) of the insect saliva by Western blot. The
      injection of immune serum previously incubated with salivary gland homogenate
      induced an early infiltration with neutrophils and macrophages, suggesting the
      participation of immune complexes in triggering inflammation.

PMID- 15728874
TI  - Variation in virulence of West Nile virus strains for house sparrows (Passer
      domesticus).
AB  - The observation of avian mortality associated with West Nile virus (WNV)
      infection has become a hallmark epidemiologic feature in the recent emergence of
      this pathogen in Israel and North America. To determine if phenotypic differences
      exist among different WNV isolates, we exposed house sparrows (Passer domesticus)
      to low passage, lineage 1 WNV strains from North America (NY99), Kenya (KEN), and
      Australia (KUN; also known as Kunjin virus). House sparrows inoculated with the
      NY99 and KEN strains experienced similar mortality rates and viremia profiles.
      The KUN strain elicited significantly lower-titered viremia when compared with
      the other strains and induced no mortality. This study suggests that natural
      mortality in house sparrows due to Old World strains of WNV may be occurring
      where the KEN strain occurs.

PMID- 15728875
TI  - Prevalence of toxocariasis in northeastern Brazil based on serology using
      recombinant Toxocara canis antigen.
AB  - To evaluate the prevalence of toxocariasis in children in Jaboatao dos
      Guararapes, Pernambuco in northeastern Brazil, 215 serum samples were examined by
      an enzyme-linked immunosorbent assay (ELISA) using a recombinant Toxocara canis
      antigen. In the ELISA, 26 (12.1%) of 215 subjects were positive. In a dot-blot
      assay using 53 of 215 serum samples, the diagnostic results correlated with those
      obtained by the ELISA. Moreover, it has been confirmed that the recombinant T.
      canis antigen was highly specific for toxocariasis by ELISA using serum samples
      positive for antibody to Ascaris lumbricoides. Considering the specificity of the
      recombinant antigen to toxocariasis, the ELISA or dot-blot assay using the
      recombinant T. canis antigen is recommended in tropical and sub-tropical regions
      where various parasitic infections are commonly endemic.

PMID- 15728879
TI  - Evaluation of ceftobiprole in a rabbit model of aortic valve endocarditis due to
      methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.
AB  - Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high
      affinity to PBP 2a, the methicillin-resistance determinant of staphylococci, and
      is active against methicillin- and vancomycin-resistant Staphylococcus aureus.
      Ceftobiprole was compared to vancomycin in a rabbit model of methicillin
      resistant S. aureus aortic valve endocarditis. Ceftobiprole and vancomycin were
      equally effective against endocarditis caused by methicillin-resistant S. aureus
      strain 76, whereas ceftobiprole was more effective than vancomycin against the
      vancomycin-intermediate S. aureus strain HIP5836. The activity of ceftobiprole
      against drug-resistant strains of S. aureus warrants its further clinical
      development.

PMID- 15728880
TI  - In vitro activity of tebipenem, a new oral carbapenem antibiotic, against
      penicillin-nonsusceptible Streptococcus pneumoniae.
AB  - The in vitro activity of tebipenem (TBM), a new oral carbapenem antibiotic,
      against Streptococcus pneumoniae clinical isolates (n = 202) was compared with
      those of 15 reference agents. The isolates were classified into five genotypic
      classes after PCR identification of abnormal pbp1a, pbp2x, and pbp2b genes: (i)
      penicillin-susceptible S. pneumoniae (PSSP) isolates with no abnormal pbp genes
      (n = 34; 16.8%), (ii) genotypic penicillin-intermediate S. pneumoniae (gPISP)
      isolates with only an abnormal pbp2x gene [gPISP (2x)] (n = 48; 23.8%), (iii)
      gPISP isolates with abnormal pbp1a and pbp2x genes (n = 32; 15.8%), (iv) gPISP
      isolates with abnormal pbp2x and pbp2b genes (n = 16; 7.9%), and (v) genotypic
      penicillin-resistant S. pneumoniae (gPRSP) isolates with three abnormal pbp genes
      (n = 72; 35.6%). The majority of the strains tested had mefA (n = 59; 29.2%) or
      ermB (n = 91; 45%) gene-mediating macrolide resistance. For these isolates the
      MIC at which 90% of isolates are inhibited was significantly lower for TBM than
      for the reference oral antibiotics, as follows: 0.002 microg/ml for PSSP, 0.004
      mug/ml for gPISP (2x), 0.016 microg/ml for gPISP (isolates with abnormal pbp1a
      and pbp2x genes and isolates with abnormal pbp2x and pbp2b genes), and 0.063
      microg/ml for gPRSP. In addition, TBM showed excellent bactericidal activity
      against gPRSP isolates, which exhibited a 3-log(10) decrease within 2 h when they
      were incubated with a concentration greater than or equal to the MIC. Inhibition
      of cell wall synthesis toward the long axis and subsequent cell lysis were
      observed by scanning electron microscopy after a short-term exposure to TBM,
      unlike the effects seen with cephalosporins. These data suggest that TBM has
      potent activity against multidrug-resistant S. pneumoniae, the causative pathogen
      of community-acquired respiratory tract infections.

PMID- 15728878
TI  - Human cytomegalovirus resistance to antiviral drugs.

PMID- 15728881
TI  - Bactericidal effects of toluidine blue-mediated photodynamic action on Vibrio
      vulnificus.
AB  - Vibrio vulnificus is a gram-negative, highly invasive bacterium responsible for
      human opportunistic infections. We studied the antibacterial effects of toluidine
      blue O (TBO)-mediated photodynamic therapy (PDT) for V. vulnificus wound
      infections in mice. Fifty-three percent (10 of 19) of mice treated with 100
      microg of TBO per ml and exposed to broad-spectrum red light (150 J/cm(2) at 80
      mW/cm(2)) survived, even though systemic septicemia had been established with a
      bacterial inoculum 100 times the 50% lethal dose. In vitro, the bacteria were
      killed after exposure to a lower light dose (100 J/cm(2) at 80 mW/cm(2)) in the
      presence of low-dose TBO (0.1 microg/ml). PDT severely damaged the cell wall and
      reduced cell motility and virulence. Cell-killing effects were dependent on the
      TBO concentration and light doses and were mediated partly through the reactive
      oxygen species generated during the photodynamic reaction. Our study has
      demonstrated that PDT can cure mice with otherwise fatal V. vulnificus wound
      infections. These promising results suggest the potential of this regimen as a
      possible alternative to antibiotics in future clinical applications.

PMID- 15728882
TI  - Emergence of resistance to rifampin and rifalazil in Chlamydophila pneumoniae and
      Chlamydia trachomatis.
AB  - Although rifamycins have excellent activity against Chlamydophila pneumoniae and
      Chlamydia trachomatis in vitro, concerns about the possible development of
      resistance during therapy have discouraged their use for treatment of chlamydial
      infections. Rifalazil, a new semisynthetic rifamycin with a long half-life, is
      the most active antimicrobial against C. pneumoniae and C. trachomatis in vitro,
      indicating its potential for treatment of acute and chronic C. pneumoniae and C.
      trachomatis infections. We investigated the effect of serial passage of two C.
      pneumoniae isolates and two serotypes of C. trachomatis in subinhibitory
      concentrations of rifalazil and rifampin on the development of phenotypic and
      genotypic resistance. C. trachomatis developed resistance to both antimicrobials
      within six passages, with higher level resistance to rifampin (128 to 256
      microg/ml) and lower level resistance to rifalazil (0.5 to 1 microg/ml). C.
      pneumoniae TW-183 developed only low-level resistance to rifampin (0.25
      microg/ml) and rifalazil (0.016 microg/ml) after 12 passages. C. pneumoniae CWL
      029 failed to develop resistance to either drug. Two unique mutations emerged in
      the rpoB gene of rifampin (L456I) and rifalazil (D461E)-resistant C. pneumoniae
      TW-183. A single mutation (H471Y) was detected in both rifampin- and rifalazil
      resistant C. trachomatis UW-3/Cx/D, and a unique mutation (V136F) was found in
      rifalazil-resistant BU-434/L(2). No mutations were detected in the entire rpoB
      gene of rifampin-resistant BU-434/L(2). This is the first description of
      antibiotic resistance-associated mutations in C. pneumoniae and of rifampin
      resistance in C. trachomatis not associated with mutations in the rpoB gene.

PMID- 15728883
TI  - Comparative bacteriological efficacy of pharmacokinetically enhanced amoxicillin
      clavulanate against Streptococcus pneumoniae with elevated amoxicillin MICs and
      Haemophilus influenzae.
AB  - A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate (2,000
      mg of amoxicillin/125 mg of clavulanate twice a day; ratio 16:1) has been
      designed, with sustained-release technology, to allow coverage of bacterial
      strains with amoxicillin-clavulanic acid MICs of at least 4/2 mug/ml. The
      bacteriological efficacy of amoxicillin-clavulanate, 2,000/125 mg twice a day,
      ratio 16:1, was compared in a rat model of respiratory tract infection versus
      four other amoxicillin-clavulanate formulations: 8:1 three times a day (1,000/125
      mg), 7:1 three times a day (875/125 mg), 7:1 twice a day (875/125 mg), and 4:1
      three times a day (500/125 mg); levofloxacin (500 mg once a day); and
      azithromycin (1,000 mg on day 1 followed thereafter by 500 mg once a day).
      Bacterial strains included Streptococcus pneumoniae, with amoxicillin-clavulanic
      acid MICs of 2/1 (one strain), 4/2, or 8/4 microg/ml (three strains each), and
      Haemophilus influenzae, one beta-lactamase-positive strain and one beta-lactamase
      negative, ampicillin-resistant strain. Animals were infected by intrabronchial
      instillation. Antibacterial treatment commenced 24 h postinfection, with doses
      delivered by computer-controlled intravenous infusion to approximate the
      concentrations achieved in human plasma following oral administration. Plasma
      concentrations in the rat corresponded closely with target human concentrations
      for all antimicrobials tested. Amoxicillin-clavulanate, 2,000/125 mg twice a day,
      ratio 16:1, was effective against all S. pneumoniae strains tested, including
      those with amoxicillin-clavulanic acid MICs of up to 8/4 microg/ml and against
      beta-lactamase-producing and beta-lactamase-negative ampicillin-resistant H.
      influenzae. These results demonstrate the bacteriological efficacy of
      pharmacokinetically enhanced amoxicillin-clavulanate 2,000/125 mg twice a day
      (ratio 16:1) against S. pneumoniae with amoxicillin-clavulanic acid MICs of at
      least 4/2 microg/ml and support clavulanate 125 mg twice a day as sufficient to
      protect against beta-lactamase in this rat model.

PMID- 15728884
TI  - Induction of fibronectin adhesins in quinolone-resistant Staphylococcus aureus by
      subinhibitory levels of ciprofloxacin or by sigma B transcription factor activity
      is mediated by two separate pathways.
AB  - We recently reported on the involvement of a RecA-LexA-dependent pathway in the
      ciprofloxacin-triggered upregulation of fibronectin-binding proteins (FnBPs) by
      fluoroquinolone-resistant Staphylococcus aureus. The potential additional
      contribution of the transcription factor sigma B (SigB) to the ciprofloxacin
      triggered upregulation of FnBPs was studied in isogenic mutants of
      fluoroquinolone-resistant strain RA1 (a topoisomerase IV gyrase double mutant of
      S. aureus NCTC strain 8325), which exhibited widely different levels of SigB
      activity, as assessed by quantitative reverse transcription-PCR of their
      respective sigB and SigB-dependent asp23 transcript levels. These mutants were
      Tn551 insertion sigB strain TE1 and rsbU(+) complemented strain TE2, which
      exhibited a wild-type SigB operon. Levels of FnBP surface display and fibronectin
      mediated adhesion were lower in sigB mutant TE1 or higher in the rsbU(+)-restored
      strain TE2 compared to their sigB(+) but rsbU parent, strain RA1, exhibiting low
      levels of SigB activity. Steady-state fnbA and fnbB transcripts levels were
      similar in strains TE1 and RA1 but increased by 4- and 12-fold, respectively, in
      strain TE2 compared to those in strain RA1. In contrast, fibronectin-mediated
      adhesion of strains TE1, RA1, and TE2 was similarly enhanced by growth in the
      presence of one-eighth the MIC of ciprofloxacin, which led to a significantly
      higher increase in their fnbB transcript levels compared to the increase in their
      fnbA transcript levels. Increased SigB levels led to a significant reduction in
      agr RNAIII; in contrast, it led to a slight increase in sarA transcript levels.
      In conclusion, upregulation of FnBPs by increased SigB levels and ciprofloxacin
      exposure in fluoroquinolone-resistant S. aureus occurs via independent pathways
      whose concerted actions may significantly promote bacterial adhesion and
      colonization.

PMID- 15728885
TI  - Single-dose pharmacokinetics and metabolism of [14C]remofovir in rats and
      cynomolgus monkeys.
AB  - Single-dose pharmacokinetics and metabolism of [(14)C]remofovir was studied in
      rats and monkeys following intravenous (i.v.) and oral administration (30 mg/kg
      of body weight). Oral absorption and bioavailability were 29.7 and 5.42% in rats
      and 65.6 and 19.4% in monkeys, respectively. Following i.v. administration, the
      elimination half-life for remofovir was 0.7 h in both rats and monkeys. Total
      body clearance was 5.85 liters/h/kg in rats and 2.60 liters/h/kg in monkeys;
      apparent volume of distribution was 5.99 liters/kg in rats and 2.70 liters/kg in
      monkeys. Following oral administration, remofovir was extensively converted to 9
      (2-phosphonylmethoxyethyl)adenine (PMEA) and other metabolites in both species.
      In rats, excretion of total radioactivity in urine accounted for 61.8% of the
      i.v. dose and 12.9% of the oral dose, while in monkeys it accounted for 43.3% of
      the i.v. dose and 34.9% of the oral dose. Following i.v. dosing of
      [(14)C]remofovir, fecal excretion of radioactivity accounted for 37.5% of the
      dose in rats and 17.4% of the dose in monkeys, indicating significant biliary
      excretion of the drug in animals. PMEA and metabolite A were the major urinary
      metabolites in both species after i.v. and oral administration of remofovir.

PMID- 15728886
TI  - Global expression of prophage genes in Escherichia coli O157:H7 strain EDL933 in
      response to norfloxacin.
AB  - We investigated the influence of a low concentration of the gyrase inhibitor
      norfloxacin on the transcriptome of enterohemorrhagic Escherichia coli O157:H7
      strain EDL933. For this purpose, we used a commercial DNA microarray containing
      oligonucleotides specific for E. coli O157:H7 strains EDL933 and RIMD0509952 and
      E. coli K-12 strain MG1655. Under the conditions applied, 5,963 spots (94% of all
      spots) could be analyzed. Among these, 118 spots (P < 0.05) indicated
      transcriptional upregulation and 122 spots (P < 0.05) indicated transcriptional
      downregulation of the E. coli genes present on the array. Eighty-five upregulated
      EDL933 genes were phage borne. Fifty-two of them could be ascribed to the Shiga
      toxin-encoding phages (Stx phages) BP-933W and CP-933V; the other 33 genes
      belonged to non-Stx prophage elements in the EDL933 genome. Genes present in the
      BP-933W prophage genome were induced most strongly up to 158-fold in the case of
      stxA(2) upon induction with norfloxacin. Twenty-two additional upregulated genes
      appeared to be E. coli O157:H7 strain RIMD0509952-specific phage elements, and
      the remaining 11 genes were related mainly to recombination and stress functions.
      Downregulation was indicated predominantly for genes responsible for bacterial
      primary metabolism, such as energy production, cell division, and amino acid
      biosynthesis. Interestingly, some genes present in the locus of enterocyte
      effacement appeared to be downregulated. The results of the study have shown that
      a low concentration of norfloxacin has profound effects on the transcriptome of
      E. coli O157:H7.

PMID- 15728887
TI  - In vitro pharmacodynamics of amphotericin B, itraconazole, and voriconazole
      against Aspergillus, Fusarium, and Scedosporium spp.
AB  - We compared the in vitro pharmacodynamics of amphotericin B, itraconazole, and
      voriconazole against Aspergillus, Fusarium, and Scedosporium species with a
      combination of two non-culture-based techniques: the tetrazolium salt 2,3-bis-(2
      methoxy-4-nitro-5-[(sulfenylamino)carbonyl]-2H-tetrazolium-hydroxide) (XTT)
      colorimetric reduction assay, and fluorescent microscopy with the cellular
      morbidity dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC) to
      directly visualize hyphal damage. Amphotericin B exhibited species-specific
      concentration-dependent activity, with 50% effective concentrations (EC(50)s)
      ranging from 0.10 to 0.12 mg/ml for A. fumigatus, 0.36 to 0.53 mg/ml for A.
      terreus, 0.27 to > or = 32 mg/ml for F. solani, 0.41 to 0.55 mg/ml for F.
      oxysporum, and 0.97 and 0.65 mg/ml for S. apiospermum and S. prolificans,
      respectively. Similarly, itraconazole inhibited the growth of A. fumigatus and A.
      terreus isolates with MICs of <1 mg/ml (EC(50) 0.03 to 0.85 mg/ml) and S.
      apiospermum, but was not active against Fusarium species or S. prolificans.
      Voriconazole effectively inhibited the growth of Aspergillus, Fusarium, and S.
      apiospermum (EC(50) 0.10 to 3.3 mg/ml) but had minimal activity against a
      multidrug-resistant isolate of F. solani or S. prolificans. Hyphal damage
      visualized by DiBAC staining was observed more frequently with voriconazole and
      amphotericin B versus itraconazole. These data highlight the species-specific
      differences in antifungal pharmacodynamics between mold-active agents that could
      be relevant for the development of in vitro susceptibility breakpoints and
      antifungal dosing in vivo.

PMID- 15728888
TI  - Phase I evaluation of the safety and pharmacokinetics of murine-derived
      anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis.
AB  - A promising approach to improving outcomes in patients with cryptococcal
      meningitis is to use adjunctive passive immunotherapy with a monoclonal antibody
      (MAb) directed against the capsular polysaccharide of Cryptococcus neoformans.
      This is the first application of MAb therapy for the treatment of a fungal
      disease in humans. We determined the safety and maximum tolerated dose of the
      murine anticryptococcal MAb 18B7 in a phase I dose-escalation study. The subjects
      were human immunodeficiency virus-infected patients who had been successfully
      treated for cryptococcal meningitis. Six dosing cohorts received MAb 18B7 at 0.01
      to 2 mg/kg of body weight as a single infusion. Three patients each received
      0.01, 0.05, 0.2, and 0.5 mg of MAb 18B7 per kg without significant adverse
      events. Four of the subjects who received the 1-mg/kg dose had mild study drug
      associated toxicity, including transient nausea, vomiting, back pain, and
      urticarial rash. Two of the subjects who received 2 mg/kg developed drug
      associated mild to moderate nausea, vomiting, chills, and myalgias. One of the
      subjects who received 2 mg/kg developed intracranial hypertension 10 weeks after
      MAb 18B7 administration. Serum cryptococcal antigen titers in the cohorts
      receiving doses of 1 and 2 mg/kg declined by a median of twofold at 1 week and a
      median of threefold at 2 weeks postinfusion, but the titers subsequently returned
      toward the baseline values by week 12. The half-life of MAb 18B7 in serum was
      approximately 53 h, while the MAb was undetectable in the cerebrospinal fluid of
      all patients. These data support the continued investigation of MAb 18B7 at a
      maximum single dose of 1.0 mg/kg.

PMID- 15728889
TI  - Open-label, dose escalation study of the safety and pharmacokinetic profile of
      tefibazumab in healthy volunteers.
AB  - Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as
      adjunctive therapy for the treatment of Staphylococcus aureus infections. This
      open-label, dose escalation study evaluated the safety and pharmacokinetics of
      tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a
      single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body
      weight infused over 15 min. Plasma samples for pharmacokinetic assessments were
      obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42,
      and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h
      after the end of the infusion, with a mean maximum concentration of drug in serum
      (C(max)) of 59, 127, 252, and 492 microg/ml following doses of 2, 5, 10, and 20
      mg/kg, respectively. The median time to maximum concentration of drug in serum
      (T(max)) was 1.0 h for each dose. The mean elimination half-life (t(1/2)) was
      approximately 22 days. The volume of distribution (V) was 4.7, 6.7, 7.2, and 7.2
      liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was
      6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels
      of tefibazumab were >100 microg/ml for 21 days. On day 56, the mean plasma
      concentrations were 6.3, 10.0, 16.4, and 30.5 microg/ml for the 2, 5, 10, and 20
      mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of
      5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in
      any subject. There were no serious adverse events, and tefibazumab was well
      tolerated over the entire dose range.

PMID- 15728890
TI  - Small-molecule inhibitors of the budded-to-hyphal-form transition in the
      pathogenic yeast Candida albicans.
AB  - The pathogenic yeast Candida albicans can exist in multiple morphological states,
      including budded, pseudohyphal, and true hyphal forms. The ability to convert
      between the budded and hyphal forms, termed the budded-to-hyphal-form transition,
      is important for virulence and is regulated by multiple environmental and
      cellular signals. To identify inhibitors of this morphological transition, a
      microplate-based morphological assay was developed. With this assay, the known
      actin-inhibiting drugs latrunculin-A and jasplakinolide were shown to inhibit the
      transition in a dose-dependent and reversible manner. Five novel small molecules
      that reversibly inhibited the transition and hyphal elongation without affecting
      budded growth were identified. These molecules inhibited hyphal growth induced by
      Spider, Lee's, M199 pH 8, and 10% serum-containing media, with two molecules
      having a synergistic effect. The molecules also differentially affected the
      hyphal form-specific gene expression of HWP1 and endocytosis without disrupting
      the actin cytoskeleton or septin organization. Structural derivatives of one of
      the molecules were more effective inhibiters than the original molecule, while
      other derivatives had decreased efficacies. Several of the small molecules were
      able to reduce C. albicans-dependent damage to endothelial cells by inhibiting
      the budded-to-hyphal-form transition. These studies substantiated the
      effectiveness of the morphological assay and identified several novel molecules
      that, by virtue of their ability to inhibit the budded-to-hyphal-form transition,
      may be exploited as starting points for effective antifungal therapeutics in the
      future.

PMID- 15728891
TI  - Molecular analysis of resistance to streptogramin A compounds conferred by the
      Vga proteins of staphylococci.
AB  - The Vga and Msr resistance determinants, encoded by mobile genetic elements in
      various staphylococcal strains, belong to a family of ATP-binding cassette (ABC)
      proteins whose functions and structures are ill defined. Their amino acid
      sequences are similar to those of proteins involved in the immunity of
      streptomycetes to the macrolide-lincosamide-streptogramin antibiotics that they
      produce. Sequence analysis of the genomes of the gram-positive bacteria with low
      G+C contents revealed that Lmo0919 from Listeria monocytogenes is more closely
      related to Vga variants than to Msr variants. In the present study we compared
      the antibiotic resistance profiles conferred by the Vga-like proteins in two
      staphylococcal hosts. It was shown that Vga(A), the Vga(A) variant [Vga(A)v], and
      Lmo0919 can confer resistance to lincosamides and streptogramin A compounds,
      while only Vga(B) is able to increase the level of resistance to pristinamycin, a
      mixture of streptogramin A and streptogramin B compounds. By using polyclonal
      antibodies, we found that the Vga(A) protein colocalized with the beta subunit of
      the F(1)-F(0) ATPase in the membrane fractions of staphylococcal cells. In order
      to identify functional units in these atypical ABC proteins, such as regions that
      might be involved in substrate specificity and/or membrane targeting, we analyzed
      the resistance phenotypes conferred by various plasmids carrying parts or
      modified versions of the vga(A) gene and we determined the subcellular
      localization of the gene products. Only polypeptides composed of two ABC domains
      were detected in the cell membranes. No region of drug specificity was
      identified. Resistance properties were dependent on the integrities of both
      Walker B motifs.

PMID- 15728892
TI  - Mechanism of action of T-705 against influenza virus.
AB  - T-705, a substituted pyrazine compound, has been found to exhibit potent anti
      influenza virus activity in vitro and in vivo. In a time-of-addition study, it
      was indicated that T-705 targeted an early to middle stage of the viral
      replication cycle but had no effect on the adsorption or release stage. The anti
      influenza virus activity of T-705 was attenuated by addition of purines and
      purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine,
      whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5'
      triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5'-monophosphate (T-705RMP)
      were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza
      virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner.
      Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA
      synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150
      fold weaker than that by ribavirin monophosphate, indicating the specificity of
      the anti-influenza virus activity and lower level of cytotoxicity of T-705. These
      results suggest that T-705RTP, which is generated in infected cells, may function
      as a specific inhibitor of influenza virus RNA polymerase and contributes to the
      selective anti-influenza virus activity of T-705.

PMID- 15728893
TI  - Biological characterization of novel inhibitors of the gram-positive DNA
      polymerase IIIC enzyme.
AB  - Novel N-3-alkylated 6-anilinouracils have been identified as potent and selective
      inhibitors of bacterial DNA polymerase IIIC, the enzyme essential for the
      replication of chromosomal DNA in gram-positive bacteria. A nonradioactive assay
      measuring the enzymatic activity of the DNA polymerase IIIC in gram-positive
      bacteria has been assembled. The 6-anilinouracils described inhibited the
      polymerase IIIC enzyme at concentrations in the nanomolar range in this assay and
      displayed good in vitro activity (according to their MICs) against staphylococci,
      streptococci, and enterococci. The MICs of the most potent derivatives were about
      4 microg/ml for this panel of bacteria. The 50% effective dose of the best
      compound (6-[(3-ethyl-4-methylphenyl)amino]-3-{[1-(isoxazol-5
      ylcarbonyl)piperidin-4-yl]methyl}uracil) was 10 mg/kg of body weight after
      intravenous application in a staphylococcal sepsis model in mice, from which in
      vivo pharmacokinetic data were also acquired.

PMID- 15728894
TI  - Pulmonary damage and bacterial load in assessment of the efficacy of simulated
      human treatment-like amoxicillin (2,000 milligrams) therapy of experimental
      pneumococcal pneumonia caused by strains for which amoxicillin MICs differ.
AB  - An experimental rat pneumonia model using two amoxicillin-susceptible (MICs, < or
      =0.015 and 2 microg/ml) and two non-amoxicillin-susceptible (MIC, 4 microg/ml)
      Streptococcus pneumoniae strains was developed for testing the efficacy of
      amoxicillin administered to simulate human serum kinetics after treatment with
      amoxicillin-clavulanate (2,000 and 125 mg, respectively, twice a day, for 2.5
      days). The end points for efficacy were reductions in bacterial loads in the
      lungs and reductions in levels of pulmonary damage. For the amoxicillin
      susceptible strains (serotypes 23F and 14), a decrease greater than 4.5 log(10)
      CFU/pair of lungs was obtained, and the time for which the serum antibiotic
      concentration (SAC) was higher than the MIC (T(S)(A)(C)(>)(MIC)) was greater than
      60% of the dosing interval. For non-amoxicillin-susceptible strains, the decrease
      in bacterial load was 1.34 to 1.75 log(10) CFU/pair of lungs, with a
      T(S)(A)(C)(>)(MIC) of 46.7% of the dosing interval. An in vitro study showed that
      serotype 9V non-amoxicillin-susceptible strains behaved as tolerant-like to
      concentrations similar to those in the in vivo model. The high and maintained
      SACs (T(S)(A)(C)(>)(MIC), >46% for all strains) significantly diminished lung
      injury (affected area of the lung and lung weight), compared to that in controls,
      by all strains, regardless of the MIC, bactericidal behavior in in vitro killing
      curves, or the serotype of the infecting strain. These results show the
      importance of host therapeutic end points in the evaluation of antibiotic
      efficacy. The antibiotic was more efficacious, for one nonsusceptible strain
      tested, when the treatment was started early (1 h postinoculation [p.i.]) than
      when treatment was delayed (24 h p.i.).

PMID- 15728895
TI  - Modified virulence of antibiotic-induced Burkholderia pseudomallei filaments.
AB  - Melioidosis is a life-threatening bacterial infection caused by Burkholderia
      pseudomallei. Some antibiotics used to treat melioidosis can induce filamentation
      in B. pseudomallei. Despite studies on the mechanism of virulence of the
      bacteria, the properties of B. pseudomallei filaments and their impact on
      virulence have not been investigated before. To understand the characteristics of
      antibiotic-induced filaments, we performed in vitro assays to compare several
      aspects of virulence between normal, nonfilamentous and filamentous B.
      pseudomallei. Normal, nonfilamentous B. pseudomallei could cause the lysis of
      monocytic cells, while filaments induced by sublethal concentrations of
      ceftazidime, ofloxacin, or trimethoprim show decreased lysis of monocytic cells,
      especially after prolonged antibiotic exposure. The motility of the filamentous
      bacteria was reduced compared to that of nonfilamentous bacteria. However, the
      filamentation was reversible when the antibiotics were removed, and the revertant
      bacteria recovered their motility and ability to lyse monocytic cells. Meanwhile,
      antibiotic resistance developed in revertant bacteria exposed to ceftazidime at
      the MIC. Our study highlights the danger of letting antibiotic concentration drop
      to the MIC or sub-MICs during antibiotic treatment of melioidosis. This could
      potentially give rise to a temporary reduction of bacterial virulence, only to
      result in bacteria that are equally virulent but more resistant to antibiotics,
      should the antibiotics be reduced or removed.

PMID- 15728897
TI  - Influence of transcriptional activator RamA on expression of multidrug efflux
      pump AcrAB and tigecycline susceptibility in Klebsiella pneumoniae.
AB  - Tigecycline is an expanded broad-spectrum antibacterial agent that is active
      against many clinically relevant species of bacterial pathogens, including
      Klebsiella pneumoniae. The majority of K. pneumoniae isolates are fully
      susceptible to tigecycline; however, a few strains that have decreased
      susceptibility have been isolated. One isolate, G340 (for which the tigecycline
      MIC is 4 microg/ml and which displays a multidrug resistance [MDR] phenotype),
      was selected for analysis of the mechanism for this decreased susceptibility by
      use of transposon mutagenesis with IS903phikan. A tigecycline-susceptible mutant
      of G340, GC7535, was obtained (tigecycline MIC, 0.25 microg/ml). Analysis of the
      transposon insertion mapped it to ramA, a gene that was previously identified to
      be involved in MDR in K. pneumoniae. For GC7535, the disruption of ramA led to a
      16-fold decrease in the MIC of tigecycline and also a suppression of MDR. Trans
      complementation with plasmid-borne ramA restored the original parental phenotype
      of decreased susceptibility to tigecycline. Northern blot analysis revealed a
      constitutive overexpression of ramA that correlated with an increased expression
      of the AcrAB transporter in G340 compared to that in tigecycline-susceptible
      strains. Laboratory mutants of K. pneumoniae with decreased susceptibility to
      tigecycline could be selected at a frequency of approximately 4 x 10(-8). These
      results suggest that ramA is associated with decreased tigecycline susceptibility
      in K. pneumoniae due to its role in the expression of the AcrAB multidrug efflux
      pump.

PMID- 15728896
TI  - Antiadenovirus activities of several classes of nucleoside and nucleotide
      analogues.
AB  - The absence of any formally licensed antiadenovirus drugs and the increasing
      incidence of life-threatening adenovirus infections in immunosuppressed patients
      warrant the development of effective antiadenovirus compounds. A detailed study
      was performed on the antiadenovirus activities of several classes of nucleoside
      and nucleotide analogues in human embryonic lung fibroblast cells. The
      antiadenovirus activities were evaluated by three methods, viz., evaluating the
      adenoviral cytopathic effect, monitoring cell viability by a colorimetric assay,
      and real-time PCR quantitation of viral DNA as a direct parameter for virus
      replication. The most active and selective compounds were the acyclic nucleoside
      phosphonate analogues cidofovir, its adenine analogue (S)-9-(3-hydroxy-2
      phosphonylmethoxypropyl)adenine [(S)-HPMPA], and the new derivative (S)-2,4
      diamino-6-[3-hydroxy-2-(phosphonomethoxy)propoxy]pyrimidine [(S)-HPMPO-DAPy]; the
      N7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine
      (S-2242); and the 2',3'-dideoxynucleoside analogues zalcitabine and alovudine. No
      antiadenovirus activity was observed for the antiviral drugs ribavirin,
      foscarnet, acyclovir, penciclovir, and brivudin, while ganciclovir displayed
      modest activity. However, in human osteosarcoma cells transfected with herpes
      simplex virus thymidine kinase, ganciclovir demonstrated highly potent
      antiadenovirus activity, suggesting that the efficacy of ganciclovir against
      adenovirus is limited by inefficient phosphorylation in adenovirus-infected
      cells, rather than by insufficient inhibition at the viral DNA polymerase level.
      Collectively, our antiviral data show that the adenovirus DNA polymerase exhibits
      sensitivity to a relatively broad spectrum of inhibitors and should be studied
      further as an antiviral target in antiadenovirus drug development programs.

PMID- 15728898
TI  - Differential bidirectional transfer of indinavir in the isolated perfused human
      placenta.
AB  - The protease inhibitor (PI) indinavir may be used in the management of human
      immunodeficiency virus (HIV) infection during pregnancy. Poor maternal-to-fetal
      transfer of indinavir has been reported previously, but the mechanisms of
      transfer remain unknown. The bidirectional transfer of indinavir was assessed in
      dually perfused, isolated human placentae. Term placentae (n = 5) were obtained
      from non-HIV-infected pregnant women. To investigate transport mechanisms, the
      steady-state transfer of indinavir was compared to those of antipyrine (a marker
      of passive diffusion) and [(3)H]vinblastine (a marker of P-glycoprotein [P-gp]
      transport) in the maternal-to-fetal and fetal-to-maternal directions in each
      placenta. Indinavir and antipyrine perfusate concentrations were determined by
      using reverse-phase, high-performance liquid chromatography; [(3)H]vinblastine
      concentrations were measured by liquid scintillation. The antipyrine transfer
      clearance in each direction did not differ (P = 0.76), a finding consistent with
      passive diffusion. However, the maternal-to-fetal transfer clearance of
      vinblastine, normalized to that of antipyrine (clearance index) (0.31 +/- 0.05),
      was significantly lower than the fetal-to-maternal clearance index of vinblastine
      (0.67 +/- 0.17; P = 0.017), suggesting the involvement of placental P-gp.
      Similarly, the maternal-to-fetal clearance index of indinavir (0.39 +/- 0.09) was
      significantly lower than its fetal-to-maternal clearance index (0.97 +/- 0.12; P
      < 0.001). These results represent the first evidence for differential transfer of
      a xenobiotic in the intact human placenta. The use of transport modulators to
      increase the maternal-to-fetal transfer of PIs as a possible strategy to reduce
      mother-to-child transmission of HIV warrants investigation.

PMID- 15728899
TI  - c-di-GMP (3'-5'-cyclic diguanylic acid) inhibits Staphylococcus aureus cell-cell
      interactions and biofilm formation.
AB  - Staphylococcus aureus is an important pathogen of humans and animals, and
      antibiotic resistance is a public health concern. Biofilm formation is essential
      in virulence and pathogenesis, and the ability to resist antibiotic treatment
      results in difficult-to-treat and persistent infections. As such, novel
      antimicrobial approaches are of great interest to the scientific, medical, and
      agriculture communities. We recently proposed that modulating levels of the
      cyclic dinucleotide signaling molecule, c-di-GMP (cyclic diguanylate [3',5'
      cyclic diguanylic acid], cGpGp), has utility in regulating phenotypes of
      prokaryotes. We report that extracellular c-di-GMP shows activity against human
      clinical and bovine intramammary mastitis isolates of S. aureus, including
      methicillin-resistant S. aureus (MRSA) isolates. We show that chemically
      synthesized c-di-GMP is soluble and stable in water and physiological saline and
      stable following boiling and exposure to acid and alkali. Treatment of S. aureus
      with extracellular c-di-GMP inhibited cell-to-cell (intercellular) adhesive
      interactions in liquid medium and reduced (>50%) biofilm formation in human and
      bovine isolates compared to untreated controls. c-di-GMP inhibited the adherence
      of S. aureus to human epithelial HeLa cells. The cyclic nucleotide analogs cyclic
      GMP and cyclic AMP had a lesser inhibitory effect on biofilms, while 5'-GMP had
      no major effect. We propose that cyclic dinucleotides such as c-di-GMP, used
      either alone or in combination with other antimicrobial agents, represent a novel
      and attractive approach in the development of intervention strategies for the
      prevention of biofilms and the control and treatment of infection.

PMID- 15728900
TI  - In vitro activity and mechanism of action of methylenecyclopropane analogs of
      nucleosides against herpesvirus replication.
AB  - We have reported previously that methylenecyclopropane analogs of nucleosides
      have excellent activity against certain members of the herpesvirus family. A
      second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and
      18 compounds were tested for activity in vitro against herpes simplex virus types
      1 and 2 (HSV-1 and HSV-2), human and murine cytomegalovirus (HCMV and MCMV),
      varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Selected analogs were
      also evaluated against human herpesvirus type 6 (HHV-6) and HHV-8. None of the 18
      compounds had activity against HSV-1 or HSV-2, but four were active against VZV
      by plaque reduction (PR) assay at 50% effective concentration (EC(50)) levels of
      < or =50 microM. Six of the 18 compounds were active against HCMV by cytopathic
      effect or PR assays with EC(50)s of 0.5 to 44 microM, and all were active against
      MCMV by PR (0.3 to 54 microM). Four of the compounds were active against EBV by
      enzyme-linked immunosorbent assay (<0.3 to 4.4 microM). Four compounds with CMV
      activity were also active against HHV-6A and HHV-6B (0.7 to 28 microM), and three
      compounds were active against HHV-8 (5.5 to 16 microM). One of these, ZSM-I-62,
      had particularly good activity against CMV, HHV-6, and HHV-8, with EC(50)s of 0.7
      to 8 microM. Toxicity was evaluated in adherent and nonadherent cells, and
      minimal cytotoxicity was observed. Mechanism of action studies with HCMV
      suggested that these compounds are phosphorylated by the ppUL97
      phosphotransferase and are potent inhibitors of viral DNA synthesis. These
      results indicate that at least one of these compounds may have potential for use
      in treating CMV and other herpesvirus infections in humans.

PMID- 15728901
TI  - Activity of gemifloxacin against quinolone-resistant Streptococcus pneumoniae
      strains in vitro and in a mouse pneumonia model.
AB  - Gemifloxacin is a novel fluoronaphthyridone quinolone with enhanced in vitro
      activity against Streptococcus pneumoniae. We investigated the activities of
      gemifloxacin and trovafloxacin, their abilities to select for resistance in vitro
      and in vivo, and their efficacies in a mouse model of acute pneumonia.
      Immunocompetent Swiss mice were infected with 10(5) CFU of a virulent,
      encapsulated S. pneumoniae strain, P-4241, or its isogenic parC, gyrA, parC gyrA,
      and efflux mutant derivatives (serotype 3); and leukopenic mice were infected
      with 10(7) CFU of two poorly virulent clinical strains (serotype 11A) carrying
      either a parE mutation or a parC, gyrA, and parE triple mutation. The drugs were
      administered six times every 12 h, starting at either 3 or 18 h postinfection. In
      vitro, gemifloxacin was the most potent agent against strains with and without
      acquired resistance to fluoroquinolones. While control mice died within 6 days,
      gemifloxacin at doses of 25 and 50 mg/kg of body weight was highly effective
      (survival rates, 90 to 100%) against the wild-type strain and against mutants
      harboring a single mutation, corresponding to area under the time-versus-serum
      concentration curve at 24 h (AUC(24))/MIC ratios of 56.5 to 113, and provided a
      40% survival rate against a mutant with a double mutation (parC and gyrA). A
      total AUC(24)/MIC ratio of 28.5 was associated with poor efficacy and the
      emergence of resistant mutants. Trovafloxacin was as effective as gemifloxacin
      against mutants with single mutations but did not provide any protection against
      the mutant with double mutations, despite treatment with a high dose of 200
      mg/kg. Gemifloxacin preferentially selected for parC mutants both in vitro and in
      vivo.

PMID- 15728902
TI  - Herpes simplex virus thymidine kinase mutations associated with resistance to
      acyclovir: a site-directed mutagenesis study.
AB  - Mutations in the thymidine kinase (TK) gene of herpes simplex virus (HSV) may
      confer resistance to acyclovir (ACV). Because of the high genetic polymorphism of
      this gene, discriminating between mutations related to resistance and mutations
      related to gene polymorphism can be difficult, especially when no sensitive
      strain has been previously isolated from the same patient. To assess the role of
      the mutations located at codons 51, 77, 83, and 175, previously detected in HSV-1
      clinical isolates (F. Morfin, G. Souillet, K. Bilger, T. Ooka, M. Aymard, and D.
      Thouvenot, J. Infect. Dis. 182:290-293, 2000), in the acquisition of resistance
      to ACV, four mutants with site-directed mutations at these respective codons were
      constructed. The enzymatic activity of the proteins, produced using both a
      reticulocyte lysate system and a bacterial system, was evaluated using
      [(3)H]thymidine as substrate. This site-directed mutagenesis revealed that
      mutations at codons 51, 83, and 175 induce a loss of HSV-1 TK activity and are
      thus clearly involved in the acquisition of resistance to ACV. On the other hand,
      the mutation at codon 77 does not affect enzyme activity.

PMID- 15728903
TI  - Transcriptional analysis of the vanC cluster from Enterococcus gallinarum strains
      with constitutive and inducible vancomycin resistance.
AB  - The vanC glycopeptide resistance gene cluster encodes enzymes required for
      synthesis of peptidoglycan precursors ending in D-Ala-D-Ser. Enterococcus
      gallinarum BM4174 and SC1 are constitutively and inducibly resistant to
      vancomycin, respectively. Analysis of peptidoglycan precursors in both strains
      indicated that UDP-MurNAc-tetrapeptide and UDP-MurNAc-pentapeptide[D-Ser] were
      synthesized in E. gallinarum SC1 only in the presence of vancomycin (4
      microg/ml), whereas the "resistance" precursors accumulated in the cytoplasm of
      BM4174 cells under both inducing and noninducing conditions. Northern
      hybridization and reverse transcription-PCR experiments revealed that all the
      genes from the cluster, vanC-1, vanXY(C), vanT, vanR(C), and vanS(C), were
      transcribed from a single promoter. In the inducible SC1 isolate, transcriptional
      regulation appeared to be responsible for inducible expression of resistance.
      Promoter mapping in E. gallinarum BM4174 revealed that the transcriptional start
      site was located 30 nucleotides upstream from vanC-1 and that the -10 promoter
      consensus sequence had high identity with that of the vanA cluster. Comparison of
      the deduced sequence of the vanS(C) genes from isolates with constitutive and
      inducible resistance revealed several amino acid substitutions located in the X
      box (R200L) and in the region between the F and G2 boxes (D312N, D312A, and
      G320S) of the putative sensor kinase proteins from isolates with constitutive
      resistance.

PMID- 15728904
TI  - CmeR functions as a transcriptional repressor for the multidrug efflux pump
      CmeABC in Campylobacter jejuni.
AB  - CmeABC, a resistance-nodulation-division (RND) type of efflux pump, contributes
      to Campylobacter resistance to a broad spectrum of antimicrobial agents and is
      also essential for Campylobacter colonization of the animal intestinal tract by
      mediation of bile resistance. As one of the main systems for Campylobacter
      adaptation to different environments, CmeABC is likely subject to control by
      regulatory elements. We describe the identification of a transcriptional
      repressor for CmeABC. Insertional mutagenesis of cmeR, an open reading frame
      immediately upstream of the cmeABC operon, resulted in overexpression of cmeABC,
      as determined by transcriptional fusion (P(cmeABC-lacZ)) and immunoblotting with
      CmeABC-specific antibodies. Overexpression of the efflux pump was correlated with
      a moderate increase in the level of resistance of the cmeR mutant to several
      antimicrobials. In vitro, recombinant CmeR bound specifically to the promoter
      region of cmeABC, precisely, to the inverted repeat sequences in the cmeABC
      promoter. A single nucleotide deletion between the two half sites of the inverted
      repeat reduced the level of CmeR binding to the promoter sequence and resulted in
      overexpression of cmeABC. Together, these findings indicate that cmeR encodes a
      transcriptional repressor that directly interacts with the cmeABC promoter and
      modulates the expression of cmeABC. Mutation either in CmeR or in the inverted
      repeat impedes the repression and leads to enhanced production of the MDR efflux
      pump.

PMID- 15728905
TI  - Synthesis and antileishmanial activities of novel 3-substituted quinolines.
AB  - The antileishmanial efficacy of four novel quinoline derivatives was determined
      in vitro against Leishmania chagasi, using extracellular and intracellular
      parasite models. When tested against L. chagasi-infected macrophages, compound 3b
      demonstrated 8.3-fold greater activity than did the standard pentavalent
      antimony. No significant activity was found for compounds 3a, 4a, and 4b. The
      antilesihmanial effect of compound 3b was independent of host cell activation, as
      demonstrated by nitric oxide production. Ultrastructural studies of promastigotes
      treated with compound 3b showed mainly enlarged mitochondria, with matrix
      swelling and reduction in the number of cristae. Synthetic analogues based on the
      quinoline ring structure, already an established template for antiparasitic
      drugs, could provide further useful compounds.

PMID- 15728906
TI  - Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and
      drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides.
AB  - Varicella-zoster virus (VZV) is responsible for primary infections as well as
      reactivations after latency in the dorsal root ganglia. The treatment of such
      infections is mandatory for immunocompromised patients and highly recommended for
      elderly patients with herpes zoster infections (also called zona or shingles).
      The treatment of choice is presently based on four molecules, acyclovir (ACV),
      valaciclovir, famciclovir, and (in Europe) brivudine (BVDU). We present here our
      data on the antiviral activity of a new class of potent and selective anti-VZV
      compounds, bicylic pyrimidine nucleoside analogues (BCNAs), against a broad
      variety of clinical isolates and different drug-resistant virus strains. The
      results show that the BCNAs are far more potent inhibitors than ACV and BVDU
      against clinical VZV isolates as well as the VZV reference strains Oka and YS.
      The BCNAs were not active against ACV- and BVDU-resistant VZV strains bearing
      mutations in the viral thymidine kinase gene but kept their inhibitory potential
      against virus strains with mutations in the VZV DNA polymerase gene. Mutant virus
      strains selected in the presence of the BCNAs were solely cross-resistant to
      drugs, such as ACV and BVDU, that depend for their antiviral action on metabolic
      activation by the viral thymidine kinase.

PMID- 15728907
TI  - Orally active antiviral tripeptide glycyl-prolyl-glycinamide is activated by CD26
      (dipeptidyl peptidase IV) before transport across the intestinal epithelium.
AB  - The tripeptide amide glycyl-prolyl-glycinamide (GPG-amide) is a new
      antiretroviral drug candidate, but its absorption mechanism is unknown. In this
      investigation, the transport and metabolism of GPG-amide were studied in a model
      of the human intestinal epithelium, Caco-2 cell monolayers. The results show that
      when the tripeptide amide came into contact with the apical enterocyte membrane,
      it was degraded by CD26 (dipeptidyl peptidase IV) to glycylproline and the
      antiretrovirally active metabolite glycinamide. Glycinamide retained
      antiretroviral activity in vitro after transport through the Caco-2 cell
      monolayers. The transport of glycinamide across Caco-2 cell monolayers occurred
      via passive diffusion with an apparent permeability coefficient of about 2 x 10(
      6) cm s(-1), which suggests that it is absorbed by the oral route in sufficient
      amounts to be considered for oral administration. In conclusion, the tripeptide
      GPG-amide acts as a prodrug that is activated by CD26 to release the orally
      active antiretroviral compound glycinamide.

PMID- 15728909
TI  - High prevalence of markers for sulfadoxine and pyrimethamine resistance in
      Plasmodium falciparum in the absence of drug pressure in the Ashanti region of
      Ghana.
AB  - Markers of Plasmodium falciparum resistance to chloroquine (CQ) and pyrimethamine
      sulfadoxine (PYR-SDX) are widespread in areas where malaria is endemic. In an
      area where the use PYR-SDX is negligible, the Ashanti Region of Ghana, West
      Africa, adult individuals were enrolled in an analysis of CQ- and PYR-SDX
      associated molecular resistance markers in 2001 (n = 177) and 2003 (n = 180).
      Parasite prevalence, as assessed by PCR assays, were 56.5 and 48.8% in 2001 and
      2003, respectively. A high frequency of CQ, PYR, and SDX resistance markers was
      observed, whereby, as a weak trend, the frequency was higher in 2003. The
      quintuple combination of three pfdhfr mutations and two pfdhps mutations has
      previously been recognized to be the most important determinant of PYR-SDX
      resistance. Approximately 60% of parasite carriers harbored fourfold mutated
      parasites, indicative of a considerable risk for a switch to high-level PYR-SDX
      resistance in an area where the rate of PYR-SDX use is low. Among the factors
      contributing to the high frequency of PYR-SDX resistance-associated mutations are
      background use of PYR-SDX, past use of PYR for malaria prophylaxis, cross
      resistance of trimethoprim with PYR, and the sufficient biological fitness of
      resistant parasites in the absence of drug pressure.

PMID- 15728908
TI  - Simocyclinone D8, an inhibitor of DNA gyrase with a novel mode of action.
AB  - We have characterized the interaction of a new class of antibiotics,
      simocyclinones, with bacterial DNA gyrase. Even though their structures include
      an aminocoumarin moiety, a key feature of novobiocin, coumermycin A(1), and
      clorobiocin, which also target gyrase, simocyclinones behave strikingly
      differently from these compounds. Simocyclinone D8 is a potent inhibitor of
      gyrase supercoiling, with a 50% inhibitory concentration lower than that of
      novobiocin. However, it does not competitively inhibit the DNA-independent ATPase
      reaction of GyrB, which is characteristic of other aminocoumarins. Simocyclinone
      D8 also inhibits DNA relaxation by gyrase but does not stimulate cleavage complex
      formation, unlike quinolones, the other major class of gyrase inhibitors;
      instead, it abrogates both Ca(2+)- and quinolone-induced cleavage complex
      formation. Binding studies suggest that simocyclinone D8 interacts with the N
      terminal domain of GyrA. Taken together, our results demonstrate that
      simocyclinones inhibit an early step of the gyrase catalytic cycle by preventing
      binding of the enzyme to DNA. This is a novel mechanism for a gyrase inhibitor
      and presents new possibilities for antibacterial drug development.

PMID- 15728910
TI  - Pharmacokinetics of gatifloxacin in infants and children.
AB  - Gatifloxacin is an 8-methoxy fluoroquinolone effective against a broad spectrum
      of pathogens common in pediatric infections. The safety and pharmacokinetics of a
      single dose of gatifloxacin were studied in pediatric patients from 6 months to
      16 years of age. Seventy-six pediatric patients (average age, 6.7 +/- 5.0 years)
      were administered a single oral dose of gatifloxacin suspension (5, 10, or 15
      mg/kg of body weight; 600-mg maximum) in a dose-escalating manner. Subjects were
      stratified by age into 4 groups. An additional 12 children, greater than 6 years
      of age, received gatifloxacin as the tablet formulation at a dose of
      approximately 10 mg/kg. Gatifloxacin's apparent clearance and half-life were 5.5
      +/- 2.1 ml/min/kg and 5.1 +/- 1.4 h. The maximum concentration of drug in plasma
      and area under the concentration-time curve (AUC) increased in a manner
      approximately proportional to the dose. At the 10-mg/kg dose, the bioavailability
      was similar between the suspension and tablet formulation. The apparent oral
      clearance of gatifloxacin, normalized for body weight, exhibited a small but
      statistically significant decrease with increasing age. In all subjects receiving
      gatifloxacin at 10 mg/kg, the AUC exceeded 20 microg . h/ml (estimated free
      AUC/MIC ratio of > or =34 for MIC of < or =0.5 microg/ml). These data suggest
      that gatifloxacin at a dose of 10 mg/kg every 24 h will achieve therapeutic
      concentrations in plasma in infants and children.

PMID- 15728911
TI  - Emergence and evolution of enfuvirtide resistance following long-term therapy
      involves heptad repeat 2 mutations within gp41.
AB  - The objective of this study was to track the evolution of sequence changes in
      both the heptad region 1 (HR1) and HR2 domains of gp41 associated with resistance
      to enfuvirtide (ENF) in a patient cohort receiving long-term ENF treatment. We
      studied 17 highly antiretroviral agent-experienced patients receiving long-term
      ENF treatment with virological rebound or a lack of suppression. Sixty-two
      samples obtained after between 5 and 107 weeks of ENF therapy were analyzed.
      Baseline samples from 15 of these 17 patients were available for analysis.
      Viruses from five samples from four patients were also sequenced after the
      cessation of ENF therapy. Drug susceptibilities were assessed by a pseudotype
      virus reporter assay. We identified HR1 and HR2 sequence changes over time in
      relation to the baseline sequences. Mutations in HR1 (amino acids 36 to 45) were
      noted in all cases, including previously unreported changes N42Q/H and N43Q. In
      addition to a range of HR2 sequence changes at polymorphic sites, isolates from 6
      of 17 (35%) patients developed an S138A substitution in the HR2 domain at least 8
      weeks after the start of ENF treatment and also subsequent to the first emergence
      of HR1 mutations. In most, but not all, cases the S138A mutation accompanied HR1
      mutations at position 43. Molecular modeling demonstrates the close proximity of
      S138A with amino acids 40 and 45 in HR1. Of note, isolates in samples available
      from four patients demonstrated the loss of both the HR1 and the S138A HR2
      mutations following the cessation of therapy. We show that the S138A HR2 mutation
      increased the level of resistance by approximately threefold over that conferred
      by the HR1 mutation N43D. Continual evolution of HR1 in the domain from amino
      acids 36 to 45 was observed during long-term ENF therapy. We have identified, for
      the first time, an ENF resistance-associated HR2 mutation, S138A, which appeared
      in isolates from 6 of 17 patients with virological failure and demonstrated its
      potential to contribute to drug resistance. We propose that this represents a
      possible secondary and/or compensatory mutation, particularly when it coexists
      with mutations at position 43 in HR-1.

PMID- 15728912
TI  - Rifampin-resistant RNA polymerase mutants of Chlamydia trachomatis remain
      susceptible to the ansamycin rifalazil.
AB  - Stable, homotypic mutants of Chlamydia trachomatis for which MICs of rifampin and
      rifalazil are elevated were isolated by serial passage at sub-MIC concentrations
      of these compounds. An alternative approach, in which Chlamydia cells were
      incubated and subsequently passaged three times, all in the presence of the
      selective agent at concentrations above the MIC, appeared to be a more effective
      means of selecting for mutants. In every instance where an elevation in the MIC
      occurred, one or more mutations in the rpoB gene, encoding the rifampin binding
      site, were detected. With one exception, all rpoB mutants that contained a single
      mutation conferred lower levels of resistance than mutants containing multiple
      mutations. Some rpoB mutations conferred very high levels of resistance to
      rifampin, up to 512 mug/ml. In all cases, mutants remained susceptible to
      concentrations of rifalazil at or below 0.064 microg/ml. Thus, rifalazil, a
      compound that is extremely potent against Chlamydia wild-type cells (MIC of
      0.00025 microg/ml), may also protect against the selection of mutants at
      physiologically achievable concentrations.

PMID- 15728913
TI  - Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis
      and cell membrane integrity in methicillin-resistant Staphylococcus aureus.
AB  - The emergence and spread of multidrug-resistant gram-positive bacteria represent
      a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic
      that possesses rapid in vitro bactericidal activity against a broad spectrum of
      clinically relevant gram-positive pathogens. Here we demonstrate that
      telavancin's antibacterial activity derives from at least two mechanisms. As
      observed with vancomycin, telavancin inhibited late-stage peptidoglycan
      biosynthesis in a substrate-dependent fashion and bound the cell wall, as it did
      the lipid II surrogate tripeptide N,N'-diacetyl-L-lysinyl-D-alanyl-D-alanine,
      with high affinity. Telavancin also perturbed bacterial cell membrane potential
      and permeability. In methicillin-resistant Staphylococcus aureus, telavancin
      caused rapid, concentration-dependent depolarization of the plasma membrane,
      increases in permeability, and leakage of cellular ATP and K(+). The timing of
      these changes correlated with rapid , concentration-dependent loss of bacterial
      viability, suggesting that the early bactericidal activity of telavancin results
      from dissipation of cell membrane potential and an increase in membrane
      permeability. Binding and cell fractionation studies provided direct evidence for
      an interaction of telavancin with the bacterial cell membrane; stronger binding
      interactions were observed with the bacterial cell wall and cell membrane
      relative to vancomycin. We suggest that this multifunctional mechanism of action
      confers advantageous antibacterial properties.

PMID- 15728914
TI  - Alpha interferon and ribavirin combination therapy of chronic hepatitis D.
AB  - The success of alpha interferon (IFN-alpha) monotherapy for the treatment of
      chronic hepatitis D is very limited. In this study, the efficacy of IFN-alpha and
      ribavirin combination therapy for chronic hepatitis D was investigated. Nineteen
      patients (15 males; mean age +/- standard deviation, 36.8 +/- 12.8 years) with
      chronic hepatitis D who were treated with IFN-alpha2b (10 million U, three
      times/week, subcutaneously) and ribavirin (1,000 to 1,200 mg/day, orally) for 24
      months were studied. All patients had compensated liver disease (15 were
      precirrhotic), elevated transaminase levels, and hepatitis D virus RNA positivity
      at baseline. Genotypic analyses revealed hepatitis D virus genotype I and
      hepatitis B virus genotype D. All patients completed the 24 months of treatment
      and at least 6 months (7 to 19 months) of a follow-up period. Biochemical
      responses were observed in eight patients (42.1%) at the end of treatment and in
      seven patients (36.8%) at the end of follow-up. Eight patients (42.1%) at the end
      of treatment and four patients (21%) at the end of follow-up had virological
      responses. In conclusion, combination treatment of IFN-alpha and ribavirin for
      chronic hepatitis D is not able to induce virological responses at a sufficient
      rate, despite its partial effectiveness in improving biochemical responses, and
      is not superior to IFN-alpha monotherapy.

PMID- 15728915
TI  - In vitro activity of structurally diverse nucleoside analogs against human
      immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase.
AB  - Human immunodeficiency virus type 1 (HIV-1) with a lysine-to-arginine
      substitution at codon 65 (HIV-1(65R)) of reverse transcriptase (RT) can rapidly
      emerge in patients being treated with specific combinations of nucleoside analog
      RT inhibitors (NRTIs). A better understanding of the activity of approved and
      investigational NRTIs against HIV-1(65R) is needed to select optimal therapy for
      patients infected with this mutant and to devise strategies to prevent its
      emergence. Therefore, we tested a broad panel of NRTIs that differed by
      enantiomer, pseudosugar, and base component against HIV-1(65R) to determine how
      NRTI structure affects activity. Drug susceptibilities of recombinant wild-type
      (HIV-1(65K)) or mutant HIV-1(65R) were determined using a single-replication
      cycle susceptibility assay with P4/R5 cells and/or a multiple-replication-cycle
      susceptibility assay with MT-2 cells. All D, L, and acyclic NRTIs were
      significantly less active against HIV-1(65R) than against HIV-1(65K) except for
      analogs containing a 3'-azido moiety. Pseudosugar structure and base component
      but not enantiomer influenced NRTI activity against HIV-1(65R). These findings
      support the inclusion of 3'-azido-3'-deoxythymidine in drug combinations to treat
      patients having HIV-1(65R) and to prevent its emergence.

PMID- 15728916
TI  - Membrane topology of the Escherichia coli AmpG permease required for recycling of
      cell wall anhydromuropeptides and AmpC beta-lactamase induction.
AB  - Escherichia coli, and presumably most other gram-negative bacteria, possesses an
      efficient protein machinery for recycling its peptidoglycan during cell growth.
      The major recycled peptidoglycan product is N-acetylglucosamine-1,6-anhydro-N
      acetylmuramic acid-tetrapeptide. Its uptake from the periplasm into the cytoplasm
      is carried out via the AmpG protein, an intrinsic membrane protein. In gram
      negative bacteria carrying an ampC beta-lactamase-inducible gene on their
      chromosomes, the induction mechanism is directly linked to peptidoglycan
      recycling. After identification of the different putative hydrophobic segments by
      computing, the AmpG topology was experimentally determined by using beta
      lactamase fusion. In the proposed model, AmpG contains 10 transmembrane segments
      and two large cytoplasmic loops.

PMID- 15728918
TI  - In vitro activity of ramoplanin against Clostridium difficile, including strains
      with reduced susceptibility to vancomycin or with resistance to metronidazole.
AB  - We evaluated the in vitro activity of ramoplanin, an antimicrobial compound that
      inhibits cell wall synthesis by acting at the level of lipid intermediate
      formation, against Clostridium difficile. We included strains with reduced
      susceptibilities to vancomycin (vancomycin-intermediate [Van(i)] strains) or with
      resistance to metronidazole (Mtz(r)), in order to assess the potential utility of
      ramoplanin for the treatment of C. difficile-associated diarrhea. We tested the
      activity of ramoplanin against a total of 105 nonduplicate clinical isolates of
      toxigenic C. difficile, including 8 Van(i) isolates and 6 Mtz(r) isolates,
      obtained from our laboratory. Ramoplanin was active against all strains tested at
      concentrations ranging from 0.03 to 0.5 microg/ml (MICs at which 50 and 90% of
      isolates were inhibited, 0.25 microg/ml; geometric mean MIC, 0.22 microg/ml). All
      isolates, independently of their levels of susceptibility to vancomycin or
      metronidazole, were considered susceptible to ramoplanin (MICs, < or =0.5
      microg/ml).

PMID- 15728917
TI  - Extended-spectrum beta-lactamases among Enterobacter isolates obtained in Tel
      Aviv, Israel.
AB  - The extended-spectrum beta-lactamase (ESBL)-producing phenotype is frequent among
      Enterobacter isolates at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
      We examined the clonal relatedness and characterized the ESBLs of a collection of
      these strains. Clonal relatedness was determined by pulsed-field gel
      electrophoresis. Isoelectric focusing (IEF) and transconjugation experiments were
      performed. ESBL gene families were screened by colony hybridization and PCR for
      bla(TEM), bla(SHV), bla(CTX-M), bla(IBC), bla(PER), bla(OXA), bla(VEB), and
      bla(SFO); and the PCR products were sequenced. The 17 Enterobacter isolates
      studied comprised 15 distinct genotypes. All isolates showed at least one IEF
      band (range, one to five bands) whose appearance was suppressed by addition of
      clavulanate; pIs ranged from 5.4 to > or = 8.2. Colony hybridization identified
      at least one family of beta-lactamase genes in 11 isolates: 10 harbored bla(TEM)
      and 9 harbored bla(SHV). PCR screening and sequence analysis of the PCR products
      for bla(TEM), bla(SHV), and bla(CTX-M) identified TEM-1 in 11 isolates, SHV-12 in
      7 isolates, SHV-1 in 1 isolate, a CTX-M-2-like gene in 2 isolates, and CTX-M-26
      in 1 isolate. In transconjugation experiments with four isolates harboring
      bla(TEM-1) and bla(SHV-12), both genes were simultaneously transferred to the
      recipient strain Escherichia coli HB101. Plasmid mapping, PCR, and Southern
      analysis with TEM- and SHV-specific probes demonstrated that a single transferred
      plasmid carried both the TEM-1 and the SHV-12 genes. The widespread presence of
      ESBLs among Enterobacter isolates in Tel Aviv is likely due not to clonal spread
      but, rather, to plasmid-mediated transfer, at times simultaneously, of genes
      encoding several types of enzymes. The dominant ESBL identified was SHV-12.

PMID- 15728919
TI  - Antiamoebic and toxicity studies of a carbamic acid derivative and its
      therapeutic effect in a hamster model of hepatic amoebiasis.
AB  - Amoebiasis is an important public health problem in developing countries.
      Entamoeba histolytica, the causative agent of amoebiasis, may develop resistance
      to nitroimidazoles, a group of drugs considered to be the most effective against
      this parasitic disease. Therefore, research on new drugs for the treatment of
      this common infection still constitutes an important therapeutic demand. In the
      present study we determined the effects of a carbamate derivative, ethyl 4
      chlorophenylcarbamate (C4), on trophozoites of E. histolytica strain HM-1:IMSS.
      C4 was subject to various toxicity tests, including the determination of
      mutagenicity for bacterial DNA and changes in the enzymatic activities of
      eukaryotic cells. Genotoxicity studies were performed by the mutagenicity Ames
      test (plate incorporation and preincubation methods) with Salmonella enterica
      serovar Typhimurium, with or without metabolic activation produced by the S9
      fraction of rat liver. C4 toxicity studies were performed by measuring enzymatic
      activity in eukaryotic cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide-formazan test with Fischer 344 rat hepatocytes. C4
      did not induce either frame-shift mutations in S. enterica serovar Typhimurium
      TA97 or TA98 or base pair substitutions in strains TA100 and TA102. The compound
      was not toxic for cultured rat hepatic cells. Trophozoites treated with 100
      microg of C4 per ml were inhibited 97.88% at 48 h of culture; moreover, damage to
      the amoebae was also confirmed by electron microscopy. The antiamoebic activity
      of C4 was evaluated by using an in vivo model of amoebic liver abscess in
      hamsters. Doses of 75 and 100 mg/100 g of body weight reduced the extent of the
      amoebic liver abscess by 84 and 94%, respectively. These results justify further
      studies to clearly validate whether C4 is a new suitable antiamoebic drug.

PMID- 15728920
TI  - Antimalarial activities and therapeutic properties of febrifugine analogs.
AB  - Febrifugine is the active principal isolated 50 years ago from the Chinese herb
      chang shan (Dichroa febrifuga Lour), which has been used as an antimalarial in
      Chinese traditional medicine for more than 2,000 years. However, intensive study
      of the properties of febrifugine has been hindered for decades due to its side
      effects. We report new findings on the effects of febrifugine analogs compared
      with those of febrifugine extracted from the dry roots of D. febrifuga. The
      properties of the extracted febrifugine were comparable to those obtained from
      the standard febrifugine provided by our collaborators. A febrifugine structure
      based computer search of the Walter Reed Chemical Information System identified
      10 analogs that inhibited parasite growth in vitro, with 50% inhibitory
      concentrations ranging from 0.141 to 290 ng/ml. The host macrophages (J744 cells)
      were 50 to 100 times less sensitive to the febrifugine analogs than the
      parasites. Neuronal (NG108) cells were even more insensitive to these drugs
      (selectivity indices, >1,000), indicating that a feasible therapeutic index for
      humans could be established. The analogs, particularly halofuginone, notably
      reduced parasitemias to undetectable levels and displayed curative effects in
      Plasmodium berghei-infected mice. Recrudescence of the parasites after treatment
      with the febrifugine analogs was the key factor that caused the death of most of
      the mice in groups receiving an effective dose. Subcutaneous treatments with the
      analogs did not cause irritation of the gastrointestinal tract when the animals
      were treated with doses within the antimalarial dose range. In summary, these
      analogs appear to be promising lead antimalarial compounds that require intensive
      study for optimization for further down-selection and development.

PMID- 15728921
TI  - Novel acyclic nucleoside phosphonate analogues with potent anti-hepatitis B virus
      activities.
AB  - Novel acyclic nucleoside phosphonates with a pyrimidine base preferentially
      containing an amino group at C-2 and C-4 and a 2-(phosphonomethoxy)ethoxy or (R)
      2-(phosphonomethoxy)propoxy group at C-6 selectively inhibit the replication of
      wild-type and lamivudine-resistant hepatitis B viruses. The activity of the most
      potent compounds was comparable to that of adefovir.

PMID- 15728922
TI  - Efficacy and toxicity of zinc salts as candidate topical microbicides against
      vaginal herpes simplex virus type 2 infection.
AB  - Zinc salt solutions administered as topical microbicides provided significant
      protection against herpes simplex virus type 2 infection in a mouse vaginal
      challenge model. However, at the therapeutic concentration, the salt solutions
      caused sloughing of sheets of vaginal epithelial cells. These observations limit
      the utility of zinc salts as microbicides and suggest that the application of
      zinc solutions to mucosal surfaces has the potential to cause damage that might
      increase susceptibility to secondary infections at a later time.

PMID- 15728923
TI  - A novel engineered peptide, a narrow-spectrum antibiotic, is effective against
      vancomycin-resistant Enterococcus faecalis.
AB  - A novel antienterococcal peptide was prepared by fusing the enterococcal cCF10
      pheromone to the channel-forming domain of colicin Ia, forming Enterococcus
      faecalis pheromonicin (PMC-EF). This peptide was bactericidal against vancomycin
      resistant Enterococcus faecalis (VRE) organisms. Electron microscopy and vital
      dyes confirmed increased membrane permeability. All mice made bacteremic with VRE
      strains survived when they were treated with PMC-EF, while all controls died.

PMID- 15728924
TI  - In vitro development of resistance to six and four fluoroquinolones in Mycoplasma
      pneumoniae and Mycoplasma hominis, respectively.
AB  - Selection of resistant mutants in sequential subcultures with increasing
      concentrations of six and four different fluoroquinolones was studied for one
      reference strain each of Mycoplasma pneumoniae and Mycoplasma hominis,
      respectively. All fluoroquinolones tested selected for resistance, with
      alterations affecting the quinolone resistance-determining regions of the four
      target topoisomerase genes.

PMID- 15728925
TI  - Integrons and transposons on the Salmonella enterica serovar typhimurium
      virulence plasmid.
AB  - A virulence plasmid was identified in a multidrug-resistant Salmonella enterica
      serotype Typhimurium strain carrying the spvC, rck, and pefA virulence genes and
      two class 1 integrons linked to the Tn21 and Tn1696 transposons. A novel
      trimethoprim resistance gene, designated dfrA23, was also identified within the
      integron region. The association of multidrug resistance and virulence
      determinants represents an interesting example of virulence plasmid evolution.

PMID- 15728926
TI  - International clone of Neisseria meningitidis serogroup A with tetracycline
      resistance due to tet(B).
AB  - Thirteen Neisseria meningitidis clinical isolates from Africa, Asia, and the
      United States for which the tetracycline MICs were elevated (> or =8 microg/ml)
      were examined for 14 recognized resistance genes. Only the drug efflux mechanism
      encoded by tet(B) was detected. All isolates were in serogroup A, belonged to
      complex ST-5, and were closely related by pulsed-field gel electrophoresis
      analysis.

PMID- 15728927
TI  - Activity of cathelicidin peptides against Chlamydia spp.
AB  - The in vitro activity of six cathelicidin peptides against 25 strains of
      Chlamydia was investigated. SMAP-29 proved to be the most active peptide,
      reducing the inclusion numbers of all 10 strains of Chlamydia trachomatis tested
      by > or =50% at 10 microg/ml. This peptide was also active against C. pneumoniae
      and C. felis.

PMID- 15728928
TI  - Antimicrobial susceptibility of Shigella sonnei isolates in Japan and molecular
      analysis of S. sonnei isolates with reduced susceptibility to fluoroquinolones.
AB  - We performed susceptibility testing with Shigella sonnei isolates from imported
      and domestic cases of infection in Japan during 2001 and 2002. Some S. sonnei
      isolates were resistant to nalidixic acid, tetracycline, and trimethoprim
      sulfamethoxazole. Most of the nalidixic acid-resistant strains showed reduced
      susceptibility to fluoroquinolones but did not show fluoroquinolone resistance.

PMID- 15728929
TI  - Deletion of the multiple-drug efflux pump AcrAB in Escherichia coli prolongs the
      postantibiotic effect.
AB  - The mechanism of the postantibiotic effect (PAE) was examined in Escherichia
      coli. Drugs exhibited longer-lasting PAEs in an acrAB mutant, suggesting that
      intracellular drug concentrations influence the duration of the PAE. With
      specific assays for tetracycline and erythromycin, a direct link between
      intracellular persistence of antibiotics and maintenance of the PAE was
      established.

PMID- 15728930
TI  - Inhaled nitric oxide treatment of patients with pulmonary tuberculosis evidenced
      by positive sputum smears.
AB  - Endogenous nitric oxide (NO) has antimycobacterial properties. We tested the
      hypothesis that exogenous (inhaled) NO can be safely delivered and can accelerate
      airway disinfection for pulmonary tuberculosis patients treated with standard
      therapy. Exogenous NO administered at 80 ppm for 72 h can be safely delivered but
      does not accelerate airway disinfection.

PMID- 15728931
TI  - Efg1 involved in drug resistance by regulating the expression of ERG3 in Candida
      albicans.
AB  - The ERG3 gene in Candida albicans was identified as a gene whose mRNA level was
      higher in the cph1/cph1 efg1/efg1 double mutant than in the wild-type cells.
      Further study showed that Efg1, but not Cph1, negatively regulated ERG3.
      Mutations in EFG1 consistently increased the susceptibility of the cells to
      antifungal agents.

PMID- 15728932
TI  - mecA is not involved in the sigmaB-dependent switch of the expression phenotype
      of methicillin resistance in Staphylococcus epidermidis.
AB  - A lack of sigma(B) activity reduces methicillin resistance in heterogeneous
      Staphylococcus epidermidis 1057, whereas inactivation of the anti-sigma factor
      RsbW switched the phenotype to homogeneous expression of resistance. Oxacillin
      induction of mecA transcription is reduced in a sigma(B)-negative strain.
      However, mecA is not involved in the switch of expression phenotype.

PMID- 15728933
TI  - Experimental bacteriophage protection against Staphylococcus aureus abscesses in
      a rabbit model.
AB  - In a rabbit model of wound infection caused by Staphylococcus aureus, 2 x 10(9)
      PFU of staphylococcal phage prevented abscess formation in rabbits when it was
      injected simultaneously with S. aureus (8 x 10(7) CFU) into the same subcutaneous
      site. Phage multiplied in the tissues. Phages might be a valuable prophylaxis
      against staphylococcal infection.

PMID- 15728934
TI  - Potential clindamycin resistance in clindamycin-susceptible, erythromycin
      resistant Staphylococcus aureus: report of a clinical failure.
AB  - The erm gene product confers clindamycin resistance on Staphylococcus aureus. We
      report a clindamycin clinical failure where resistance developed on therapy in a
      D-test-positive strain. D tests of 91 clindamycin-susceptible, erythromycin
      resistant S. aureus isolates showed that 68% of methicillin-susceptible and 12.3%
      of methicillin-resistant S. aureus strains were D-test positive.

PMID- 15728935
TI  - Synergistic killing of Streptococcus pneumoniae with the bacteriophage lytic
      enzyme Cpl-1 and penicillin or gentamicin depends on the level of penicillin
      resistance.
AB  - A combination of Cpl-1, a bacteriophage lytic enzyme, and penicillin, gentamicin,
      levofloxacin, or azithromycin was tested against Streptococcus pneumoniae strains
      with various susceptibilities to penicillin. Activities of Cpl-1 and gentamicin
      were increasingly synergistic with a decreasing penicillin MIC, while Cpl-1 and
      penicillin showed synergy against an extremely penicillin-resistant strain.

PMID- 15728936
TI  - Disequilibrium in distribution of resistance mutations among Mycobacterium
      tuberculosis Beijing and non-Beijing strains isolated from patients in Germany.
AB  - Genotypic analysis of 103 multidrug-resistant Mycobacterium tuberculosis strains
      isolated in Germany in 2001 revealed that mutations in codon 531 (75.7%) of the
      rpoB gene and codon 315 (88.4%) of the katG gene are most frequent. Beijing
      genotype strains (60.2% of all isolates) displayed a different distribution of
      resistance mutations than non-Beijing strains.

PMID- 15728938
TI  - Mutational analysis of metronidazole resistance in Helicobacter pylori.
AB  - Metronidazole is one of a few antibiotics effective in eliminating Helicobacter
      pylori infection of the human stomach. Several chromosomal loci have been
      implicated in resistance to this drug. Saturation transposon mutagenesis of the
      H. pylori genome revealed inactivation of the rdxA gene as uniquely able to
      confer metronidazole resistance.

PMID- 15728937
TI  - Combined activity in vitro of caspofungin, amphotericin B, and azole agents
      against itraconazole-resistant clinical isolates of Aspergillus fumigatus.
AB  - Interactions in vitro between amphotericin B, itraconazole, voriconazole, and
      caspofungin against itraconazole-resistant Aspergillus fumigatus clinical strains
      were determined. Differential results were obtained depending on the criteria
      (MIC or minimal effective concentration) used. Caspofungin and voriconazole
      exhibited the most potent interactions, with synergy against at least 50% of
      isolates, and the average fractional concentration index was 0.38. Antagonism was
      not found for any combination.

PMID- 15728939
TI  - New integron-associated gene cassette encoding a 3-N-aminoglycoside
      acetyltransferase.
AB  - A fifth gene cassette containing an aacC gene, aacCA5, was found in an aacCA5
      aadA7 cassette array in a class 1 integron isolated from a multiply drug
      resistant Salmonella enterica serovar Kentucky strain. The AacC-A5 or AAC(3)-Ie
      acetyltransferase encoded by aacCA5 is related to other AAC(3)-I enzymes and
      confers resistance to gentamicin.

PMID- 15728940
TI  - Experimental prediction of the evolution of ceftazidime resistance in the CTX-M-2
      extended-spectrum beta-lactamase.
AB  - We applied in vitro evolution to an Escherichia coli strain containing bla(CTX-M
      2) and obtained 10 independent mutant bla(CTX-M-2) alleles that confer elevated
      resistance to ceftazidime (MIC > or = 32 microg/ml) but lost the ability to
      confer resistance to cefepime. All alleles had a Pro-to-Ser substitution at
      position 167.

PMID- 15728941
TI  - Susceptibility of Streptococcus mutans and Actinobacillus actinomycetemcomitans
      to bactericidal activity of human beta-defensin 3 in biological fluids.
AB  - Bactericidal activity of human beta-defensin 3 (hBD-3) against Streptococcus
      mutans and Actinobacillus actinomycetemcomitans was inhibited in a dose-dependent
      manner by the presence of saliva and/or serum. Increasing the concentration of
      hBD-3 partially overcame this inhibition. A fast bactericidal effect was observed
      against both bacterial strains, suggesting a potential therapeutic use for hBD-3
      in the local treatment of oral infections.

PMID- 15728942
TI  - In vitro activity of the histatin derivative P-113 against multidrug-resistant
      pathogens responsible for pneumonia in immunocompromised patients.
AB  - The in vitro activity of the histatin derivative P-113, alone or combined with
      eight antibiotics, was investigated against multidrug-resistant strains isolated
      from clinical specimens of immunocompromised patients with pneumonia. The gram
      negative isolates were susceptible to P-113. S. aureus showed less
      susceptibility. Synergy was demonstrated when P-113 was combined with beta
      lactams against gram-negative organisms.

PMID- 15728943
TI  - Inducible metronidazole resistance and nim genes in clinical Bacteroides fragilis
      group isolates.
AB  - Nitroimidazole resistance (nim) genes were detected in 2% of 1,502 clinical
      Bacteroides fragilis group strains isolated from 19 European countries, and a
      novel nim gene was identified. High metronidazole resistance could be induced in
      nim-positive strains, which emphasizes the importance of acknowledging
      metronidazole resistance in the clinical setting.

PMID- 15728944
TI  - Molecular epidemiology and prevalence of macrolide efflux genes mef(A) and mef(E)
      in Streptococcus pneumoniae obtained in Canada from 1997 to 2002.
AB  - One hundred forty M phenotype Streptococcus pneumoniae isolates were evaluated by
      PCR-restriction fragment length polymorphism, serotyping, and pulsed-field gel
      electrophoresis. Molecular genotyping revealed that the predominant macrolide
      resistance mechanism in S. pneumoniae in Canada is mef(E) and resistance
      dissemination is due to both spread of the genetic element MEGA as well as clonal
      dissemination of penicillin- and/or macrolide-resistant strains.

PMID- 15728945
TI  - Monitoring and characterization of extended-spectrum beta-lactamases in
      Escherichia coli strains from healthy and sick animals in Spain in 2003.
AB  - Genes encoding CTX-M-14, CTX-M-9, CTX-M-1, CTX-M-32, SHV-12, TEM-52, or CMY-2
      beta-lactamases were detected in 21 Escherichia coli strains recovered during
      2003 from sick animals (11 of 459 [2.4%] strains) and healthy animals (10 of 158
      [6.3%] strains) in Spain. Twelve of these strains harbored bla(CTX-M) genes and
      showed unrelated pulsed-field gel electrophoresis patterns.

PMID- 15728946
TI  - Hybrid tet genes and tet gene nomenclature: request for opinion.

PMID- 15728947
TI  - Evolution of transposons containing blaTEM genes.

PMID- 15728949
TI  - First, do no harm.

PMID- 15728950
TI  - Methemoglobinemia in critically ill burned patients.

PMID- 15728951
TI  - Methemoglobinemia in critically ill burned patients.

PMID- 15728952
TI  - Adjunctive use of plasmapheresis and intravenous immunoglobulin therapy in
      sepsis: a case report.

PMID- 15728953
TI  - Time out! Is timepiece variability a factor in critical care?
AB  - BACKGROUND: Accurate documentation of time is essential in critical care for
      treatments, interventions, research, and medicolegal and quality improvement
      activities. OBJECTIVES: To assess use of timepieces in critical care and to
      determine practical methods for improving their accuracy. METHODS: Providers were
      surveyed to identify timepieces used during routine and emergency care. Times
      displayed on standard unit and personal timepieces were compared with coordinated
      universal time. Four models of atomic clocks were assessed for drift for 6 weeks
      and for resynchronization for 1 week. Bedside monitors were manually synchronized
      to coordinated universal time and were assessed for drift. RESULTS: Survey
      response was 78% (149/190). Nurses (n = 93), physicians (n = 32), and respiratory
      therapists (n = 24) use wall clocks (50%) and personal timepieces (46%) most
      frequently during emergencies. The difference from coordinated universal time was
      a median of -4 minutes (range, -5 minutes to +2 min) for wall clocks, -2.5
      minutes (-90 minutes to -1 minute) for monitors, and 0 minutes (-22 minutes to
      +12 minutes) for personal timepieces. Kruskal-Wallis testing indicated
      significant variations for all classes of timepieces (P<.001) and for personal
      timepieces grouped by discipline (P=.02). Atomic clocks were accurate to 30
      seconds of coordinated universal time for 6 weeks when manually set but could not
      be synchronized by radiofrequency signal. Drift of bedside monitors was 1 minute.
      CONCLUSIONS: Timepieces used in critical care are highly variable and inaccurate.
      Manually synchronizing timepieces to coordinated universal time improved accuracy
      for several weeks, but the feasibility of synchronizing all timepieces is
      undetermined.

PMID- 15728954
TI  - Outcomes of care managed by an acute care nurse practitioner/attending physician
      team in a subacute medical intensive care unit.
AB  - BACKGROUND: Many academic medical centers employ nurse practitioners as
      substitutes to provide care normally supplied by house staff. OBJECTIVE: To
      compare outcomes in a subacute medical intensive care unit of patients managed by
      a team consisting of either an acute care nurse practitioner and an attending
      physician or an attending physician and critical care/pulmonary fellows. METHODS:
      During a 31-month period, in 7-month blocks of time, 526 consecutive patients
      admitted to the unit for more than 24 hours were managed by one or the other of
      the teams. Patients managed by the 2 teams were compared for a variety of
      outcomes. RESULTS: Patients managed by the 2 teams did not differ significantly
      for any workload, demographic, or medical condition variable. The patients also
      did not differ in readmission to the high acuity unit (P = .25) or subacute unit
      (P = .44) within 72 hours of discharge or in mortality with (P = .25) or without
      (P = .89) treatment limitations. Among patients who had multiple weaning trials,
      patients managed by the 2 teams did not differ in length of stay in the subacute
      unit (P = .42), duration of mechanical ventilation (P = .18), weaning status at
      time of discharge from the unit (P = .80), or disposition (P = .28). Acute
      Physiology Scores were significantly different over time (P = .046). Patients
      managed by the fellows had more reintubations (P=.02). CONCLUSIONS: In a subacute
      intensive care unit, management by the 2 teams produced equivalent outcomes.

PMID- 15728955
TI  - Use of physical restraints in adult critical care: a bicultural study.
AB  - BACKGROUND: Although controversial, physical restraints are commonly used in
      adult critical care units in the United States to prevent treatment interference
      and self-inflicted harm. Use of physical restraints in Norwegian hospitals is
      very limited. In the United States, an experimental design for research on use of
      restraints has not seemed feasible. However, international research provides an
      opportunity to compare and contrast practices. OBJECTIVES: To describe the
      relationship between patients' characteristics, environment, and use of physical
      restraints in the United States and Norway. METHODS: Observations of patients and
      chart data were collected from 2 intensive care units (n = 50 patients) in Norway
      and 3 (n = 50 patients) in the United States. Sedation was measured by using the
      Sedation-Agitation Scale. The Nine Equivalents of Nursing Manpower Use Score was
      used to indicate patients' acuity level. RESULTS: Restraints were in use in 39 of
      100 observations in the United States and not at all in Norway (P = .001).
      Categories of patients were balanced. In the Norwegian sample, the median Nine
      Equivalents of Nursing Manpower Use Score was higher (37 vs 27 points, P < .001),
      patients were more sedated (P < .001), and nurse-to-patient ratios were higher
      (1.05:1 vs 0.65:1, P < .001). Seven incidents of unplanned device removal were
      reported in the US sample. CONCLUSIONS: Critical care units with similar
      technology and characteristics of patients vary between nations in restraint
      practices, levels of sedation, and nurse-to-patient ratios. Restraint-free care
      was, in this sample, safe in terms of treatment interference.

PMID- 15728956
TI  - The lived experience of spouses of patients with a left ventricular assist device
      before heart transplantation.

PMID- 15728957
TI  - The lived experience of spouses of patients with a left ventricular assist device
      before heart transplantation.
AB  - BACKGROUND: No publications describe the life experience of spouses who are
      designated caregivers of patients with a left ventricular assist device before
      transplantation. OBJECTIVE: To explore what life is like for spouses serving as
      caregivers of patients with a left ventricular assist device before
      transplantation and to assess the meaning of such experience to them. METHODS:
      This phenomenological study included 3 women 38 to 52 years old who were
      designated caregivers of patients with a left ventricular assist device while the
      patients were waiting at home for a heart transplant. RESULTS: Three major themes
      emerged-emotional distress, determination, and optimism: a new lease on life. The
      identified themes were elucidated by 8 subthemes: guilt and realization of
      severity of illness, fear and anxiety, recognition that being a caregiver is an
      overwhelming experience and a burden, coping, living with hope, realization of
      loving relationship, adaptation to a new life, and joyful feeling. CONCLUSION:
      The spouses who served as caregivers had strong emotions as they entered each
      stage of this life experience. The stages were characterized by the identified
      themes and subthemes, which otherwise might not have been revealed or might have
      remained private to the study participants. Critical care nurses should recognize
      and anticipate challenges for these stages of life experienced by the spouses as
      caregivers. Heightened awareness of this phenomenon will guide nurses in
      individualizing plans of care, educating patients and patients' families, and
      evaluating outcomes of care.

PMID- 15728958
TI  - Honoring the good behind rights and justice in healthcare when more than justice
      is needed.

PMID- 15728959
TI  - Estrogen plus progestin, benefits and risks: the "Women's Health Initiative"
      trials.

PMID- 15728960
TI  - Nonrespiratory sinus arrhythmia.

PMID- 15728964
TI  - An X-ray nanodiffraction technique for structural characterization of individual
      nanomaterials.
AB  - An X-ray micro/nanodiffraction technique that allows structural characterization
      of individual nanomaterials has been developed at an insertion-device beamline of
      the Advanced Photon Source. Using the extremely high brightness of the third
      generation synchrotron radiation source and advanced high-resolution high-energy
      zone-plate focusing optics, X-rays of energies from 6 to 12 keV have been focused
      into a spot smaller than 200 nm with a photon density gain of more than 50,000 so
      that significant photon flux can be intercepted by a nanoscale material to
      generate a measurable diffraction signal for structural characterization. This
      paper describes the instrumentation of the technique and discusses the
      application of the technique to studies of tin oxide nanobelts.

PMID- 15728965
TI  - Synchrotron and simulations techniques applied to problems in materials science:
      catalysts and Azul Maya pigments.
AB  - Development of synchrotron techniques for the determination of the structure of
      disordered, amorphous and surface materials has exploded over the past 20 years
      owing to the increasing availability of high-flux synchrotron radiation and the
      continuing development of increasingly powerful synchrotron techniques. These
      techniques are available to materials scientists who are not necessarily
      synchrotron scientists through interaction with effective user communities that
      exist at synchrotrons such as the Stanford Synchrotron Radiation Laboratory. In
      this article the application of multiple synchrotron characterization techniques
      to two classes of materials defined as 'surface compounds' is reviewed. One class
      of surface compounds are materials like MoS(2-x)C(x) that are widely used
      petroleum catalysts, used to improve the environmental properties of
      transportation fuels. These compounds may be viewed as 'sulfide-supported
      carbides' in their catalytically active states. The second class of 'surface
      compounds' are the 'Maya blue' pigments that are based on technology created by
      the ancient Maya. These compounds are organic/inorganic 'surface complexes'
      consisting of the dye indigo and palygorskite, common clay. The identification of
      both surface compounds relies on the application of synchrotron techniques as
      described here.

PMID- 15728966
TI  - Synchrotron radiation and high pressure: new light on materials under extreme
      conditions.
AB  - With the steady development of static high-pressure techniques in recent years,
      it is now possible to probe in increasing detail the novel behavior of materials
      subjected to extreme conditions of multimegabar pressures (>300 GPa) and
      temperatures from cryogenic states to thousands of degrees. By and large, the
      growth in this area has been made possible by accelerating developments in
      diamond-anvil cell methods coupled with new synchrotron radiation techniques.
      Significant advances have occurred in high-pressure powder and single-crystal
      diffraction, spectroscopy, inelastic scattering, radiography, and infrared
      spectroscopy. A brief overview of selected highlights in each of these classes of
      experiments is presented that illustrate both the state-of-the-art as well as
      current technical and scientific challenges. The experiments have been made
      possible by the development of a spectrum of new techniques at both third- and
      second-generation high-energy sources together with key advances in high-pressure
      technology. The results have implications for a variety of problems in physics,
      chemistry, materials science, geoscience, planetary science, and biology.

PMID- 15728967
TI  - Polychromatic X-ray microdiffraction studies of mesoscale structure and dynamics.
AB  - Polychromatic X-ray microdiffraction is an emerging tool for studying mesoscale
      structure and dynamics. Crystalline phase, orientation (texture), elastic and
      plastic strain can be nondestructively mapped in three dimensions with good
      spatial and angular resolution. Local crystallographic orientation can be
      determined to approximately 0.01 degree and elastic strain tensor elements can be
      measured with a resolution of approximately 10(-4) or better. Complete strain
      tensor information can be obtained by augmenting polychromatic microdiffraction
      with a monochromatic measurement of one Laue-reflection energy. With differential
      aperture depth profiling, volumes tens to hundreds of micrometers below the
      surface are accessible so that three-dimensional distributions of crystalline
      morphology including grain boundaries, triple points, second phases and
      inclusions can all be mapped. Volume elements below 0.25 microm3 are routinely
      resolved so that the grain boundary structure of most materials can be
      characterized. Here the theory, instrumentation and application of polychromatic
      microdiffraction are described.

PMID- 15728968
TI  - In situ synchrotron X-ray studies of ferroelectric thin films.
AB  - In situ synchrotron X-ray scattering was used to observe both the growth of
      PbTiO3 films by metal-organic chemical vapour deposition and the behaviour of the
      ferroelectric phase transition as a function of film thickness. The dependences
      of growth mode and deposition rate on gas flows and substrate temperature were
      determined by homoepitaxial growth studies on thick films (>50 nm). These studies
      facilitated the growth of thin coherently strained PbTiO3 films on SrTiO3 (001)
      substrates, with thicknesses ranging from 2 to 42 nm. Experiments on the
      ferroelectric phase transition as a function of film thickness were carried out
      in these films under controlled mechanical and electrical boundary conditions.

PMID- 15728969
TI  - Linear and circularly polarized light to study anisotropy and resonant scattering
      in magnetic thin films.
AB  - The remarkable polarization properties of synchrotron light have lead to the
      advent of modern synchrotron-related spectroscopic studies with angular and/or
      magnetic selectivity. Here an overview is given of the prominent aspects of the
      polarization of the light delivered by a bending magnet, and some dichroic
      properties in X-ray absorption spectroscopy (XAS). Two studies developed at the
      Brazilian Synchrotron Light Laboratory are then reported, exemplifying the profit
      gained using linear and circular polarization of X-rays for the study of magnetic
      thin films and multilayers. Angle-resolved XAS was used in strained manganite
      thin films to certify a model of local distortion limited within the MnO6
      polyhedron. A pioneering experience of X-ray magnetic scattering at grazing
      incidence associated with dispersive XAS in a Co/Gd multilayer draws new
      perspectives for magnetic studies in thin films and multilayers under atmospheric
      conditions in the hard X-ray range.

PMID- 15728970
TI  - X-ray synchrotron studies of ultrafast crystalline dynamics.
AB  - Ultrafast X-ray experiments at synchrotron sources hold tremendous promise for
      measuring the atomistic dynamics of materials under a wide variety of transient
      conditions. In particular, the marriage of synchrotron radiation and ultrafast
      laser technology is opening up a new frontier of materials research. Structural
      changes initiated by femtosecond laser pulses can be tracked in real time using
      time-resolved X-ray diffraction on picosecond time scales or shorter. Here,
      research at the Advanced Photon Source is described, illustrating the
      opportunities for ultrafast diffraction with some recent work on the generation
      of impulsive strain, coherent phonon generation and supersonic diffusion of
      electron-hole plasmas. The flexibility of time-resolved Bragg and Laue
      diffraction geometries are both utilized to illuminate the strain generation and
      evolution process. Time-resolved X-ray science will become increasingly important
      with the construction of linac-based ultrafast X-ray sources.

PMID- 15728971
TI  - Local structure fluctuations as a signature of an inhomogeneous ground state in
      high-Tc superconductors.
AB  - In-plane polarized Cu K-edge XAFS on La2CuO4.1 is presented, which indicates a
      radial in-plane Cu-O distribution function that is not a single Gaussian. Fits to
      the isolated Cu-O XAFS signal show the presence of a two-site radial distribution
      function, similar to that found in other La-based cuprate superconductors at
      temperatures below the temperature associated with the pseudogap appearance, T*.
      The appearance of the two-site distribution is interpreted as evidence of a non
      homogeneous ground state, preceding the superconducting transition. Similar
      results found in other copper-oxide superconductors indicate that this non
      homogeneous ground state is a general feature of these materials.

PMID- 15728972
TI  - X-ray vision of fuel sprays.
AB  - With brilliant synchrotron X-ray sources, microsecond time-resolved synchrotron X
      ray radiography and tomography have been used to elucidate the detailed three
      dimensional structure and dynamics of high-pressure high-speed fuel sprays in the
      near-nozzle region. The measurement allows quantitative determination of the fuel
      distribution in the optically impenetrable region owing to the multiple
      scattering of visible light by small atomized fuel droplets surrounding the jet.
      X-radiographs of the jet-induced shock waves prove that the fuel jets become
      supersonic under appropriate injection conditions and that the quantitative
      analysis of the thermodynamic properties of the shock waves can also be derived
      from the most direct measurement. In other situations where extremely axial
      asymmetric sprays are encountered, mass deconvolution and cross-sectional fuel
      distribution models can be computed based on the monochromatic and time-resolved
      X-radiographic images collected from various rotational orientations of the
      sprays. Such quantitative analysis reveals the never-before-reported
      characteristics and most detailed near-nozzle mass distribution of highly
      transient fuel sprays.

PMID- 15728974
TI  - A new cell for temperature-dependent X-ray absorption spectroscopy of liquid
      solutions: application to PbBr2 solutions in diethylene glycol.
AB  - An in situ cell has been constructed for temperature-dependent X-ray absorption
      experiments (EXAFS and XANES) of lead bromine (PbBr2) solutions in diethylene
      glycol in the temperature range from room temperature up to about 433 K. The
      solution is kept in a thermostated container made of carbon-reinforced teflon
      between two thin chemically inert quartz glass windows with a high transmission
      for hard X-rays. The construction of the cell ensures that these X-ray windows
      are thermalized so that any possible precipitation of solid products from the
      solution is inhibited. The cell consists mainly of two hermetically sealed teflon
      containers for the thermostating fluid (silicon oil) that were fitted together in
      such a way that a small and variable volume (approximately 2-4 cm3) for the
      liquid under investigation was achieved. A small thermocouple in a glass
      enclosure was placed in the solution to maintain temperature control and feedback
      to the thermostat. The cell design and its performance for temperature-dependent
      in situ investigations with X-rays are reported. Some preliminary results
      obtained for PbBr2 solutions in diethylene glycol are given.

PMID- 15728975
TI  - Specimen charging in X-ray absorption spectroscopy: correction of total electron
      yield data from stabilized zirconia in the energy range 250-915 eV.
AB  - The effects of specimen charging on X-ray absorption spectroscopy using total
      electron yield have been investigated using powder samples of zirconia stabilized
      by a range of oxides. The stabilized zirconia powder was mixed with graphite to
      minimize the charging but significant modifications of the intensities of
      features in the X-ray absorption near-edge fine structure (XANES) still occurred.
      The time dependence of the charging was measured experimentally using a time
      scan, and an algorithm was developed to use this measured time dependence to
      correct the effects of the charging. The algorithm assumes that the system
      approaches the equilibrium state by an exponential decay. The corrected XANES
      show improved agreement with the electron energy-loss near-edge fine structure
      obtained from the same samples.

PMID- 15728973
TI  - ID22: a multitechnique hard X-ray microprobe beamline at the European Synchrotron
      Radiation Facility.
AB  - The ID22 beamline is dedicated to hard X-ray microanalysis allowing the
      combination of fluorescence, spectroscopy, diffraction and tomography techniques
      in a wide energy range from 6 to 70 keV. The recent installation of an in-vacuum
      undulator, a new sample stage and the adaptation of various focusing optics has
      contributed to a great improvement in the capabilities of the beamline, which is
      now accessed by a wide user community issued from medical, earth and
      environmental science, archaeology and material science. Many applications
      requiring low detection limits for localization/speciation of trace elements
      together with structural analysis have been developed at the beamline on the
      (sub)micrometer scale. The possibility of combining simultaneously different
      analytical probes offers the opportunity of a thorough study of a given sample or
      scientific problem. This paper presents a review of the recent developments of
      the beamline and a detailed description of its capabilities through examples from
      different fields of applications.

PMID- 15728976
TI  - Determination of the metal ordering in meteoritic (Fe,Ni)3P crystals.
AB  - Synchrotron radiation diffraction studies of meteoritic (Fe,Ni)3P crystals have
      been performed to reveal the ordering of the elements Fe and Ni on the three
      metal sites M1, M2 and M3 of the unit cell. The delta synthesis technique, which
      is a two-wavelength method using anomalous dispersion effects, was applied. For
      (Fe,Ni) phosphide crystals with different Fe:Ni ratios extracted from different
      meteorites, it was found that Ni occupies the M3 site and also partially the M2
      site, avoiding the M1 position, whereas the M1 site is preferentially occupied by
      Fe. In connection with earlier results known from the literature, this metal
      distribution seems to be characteristic of this compound, and is independent of
      thermodynamic formation conditions.

PMID- 15728977
TI  - Phase-contrast X-ray imaging combining free space propagation and Bragg
      diffraction.
AB  - The combination of X-ray 'propagation-based' and 'analyzer-based' phase-contrast
      imaging with a perfect crystal-analyzer is investigated. The image pattern
      produced using this 'hybrid' imaging technique presents peculiar features that
      can be interpreted as a mixture of the two independent phase-contrast signals. A
      quantitative analysis has been performed in terms of signal-to-noise ratio for
      the three techniques considered in this paper. Results show that in the 'hybrid
      imaging' technique this parameter has a weaker dependence on the angular
      alignment of the crystal analyser with respect to the 'analyser-based' imaging.
      This pioneering experiment indicates that this hybrid imaging technique might
      permit simultaneous advantage of the specific features of the two imaging methods
      to be taken.

PMID- 15728978
TI  - An internet-based synchrotron experiment for students measuring the X-ray
      magnetic circular dichroism of a PtFe alloy.
AB  - A new internet-based synchrotron experiment for students is presented. A
      polarimeter and computer software have been developed for measuring via the
      internet the X-ray magnetic circular dichroism of PtFe around its Pt L(II) and
      L(III) absorption edges. From the experiment, students can examine the X-ray
      magnetic circular dichroism of a thin PtFe foil utilizing circular-polarized
      synchrotron radiation emitted by the superconducting asymmetric wiggler at the
      synchrotron radiation source DELTA of the University of Dortmund.

PMID- 15728979
TI  - On the imaging of the flux-line lattice of a type-II superconductor by soft X-ray
      absorption microscopy.
AB  - A new method is proposed for the imaging of the flux-line lattice of a type-II
      superconductor by soft X-ray absorption microscopy. It is shown that the method
      is very demanding but probably realisable in the foreseeable future. The new
      method has the potential to image in real space static and dynamical properties
      of the flux-line lattice at arbitrary external fields and with single-flux-line
      resolution.

PMID- 15728981
TI  - Functional analysis of fungal drug efflux transporters by heterologous expression
      in Saccharomyces cerevisiae.
AB  - Clinically important resistance of fungal pathogens to azole antifungal drugs is
      most frequently caused by the over-expression of energy-dependent drug efflux
      pumps. These pumps usually belong to either the ATP-binding cassette (ABC) family
      or the Major Facilitator Superfamily (MFS) class of membrane transporter. Little
      is known about how these pumps work and there is an urgent need to develop pump
      antagonists that circumvent azole resistance. We have developed a protein hyper
      expression system to facilitate functional analysis of efflux pumps based on a
      Saccharomyces cerevisiae host which has been deleted in seven major ABC
      transporters to reduce the background of endogenous efflux activity. Plasmid
      pABC3 was engineered to allow functional hyper-expression of foreign proteins in
      this host. The main advantages of the system include its ease of directional
      cloning and the use of homologous recombination to stably integrate single copy
      constructs into the host genome under the control of a highly active
      transcriptional regulator. The system has been used to clone and functionally
      hyper-express genes encoding drug efflux pumps from several pathogenic fungi.
      Furthermore, the protein hyper-expression system has been used to screen for pump
      inhibitors and study the structure and function of heterologous membrane
      proteins.

PMID- 15728982
TI  - A six-year study on Vibrio cholerae in southeastern Iran.
AB  - Cholera continues to be an important public health problem among many poorer
      communities. In order to determine the epidemiology of Vibrio cholerae in
      southeastern Iran, 3,594 patients with watery diarrhea, who were referred to the
      hospitals from Zabol city and 45 neighboring rural populations of Sistan
      Blouchestan province, were investigated over a period of 6 years (1997 - 2002).
      V. cholerae strains were isolated from 362 samples (10.07%). Isolation of V.
      cholerae in this sample decreased from 22.47% in 1997 to 0% in 2002. Individuals
      of all ages and social and economic strata were affected. Among the patients with
      cholera in the present study, only 24 (6.6%) lived in an urban area; 270 (74.6%)
      of the patients had been referred from rural areas, and the remaining 68 (18.8%)
      were from neighboring Afghanistan. V. cholerae O1 Ogawa and NAG vibrios were
      found in 92.8 and 7.2% of patients, respectively. Among the 362 samples, 244 were
      collected from inpatients and 118 were from outpatients. Twelve of these patients
      died because of the severity of their disease, severe dehydration and
      electrolytes imbalance. The priorities for cholera control remain public health
      interventions through improved water and sanitation, improved surveillance and
      access to health care facilities, and further development of appropriate
      vaccines.

PMID- 15728983
TI  - Significant elevation of serum soluble CD14 levels in patients with brucellosis.
AB  - Activation of macrophages represents one of the initial events in innate immunity
      to intracellular infections. CD14 is expressed principally by cells of
      monocyte/macrophage lineage and plays a pivotal role in innate recognition of
      bacterial cell wall components, particularly lipopolysaccharides. We measured
      serum concentrations of soluble CD14 (sCD14) in serum samples obtained from 37
      patients with brucellosis and 36 healthy controls. Serum levels of sCD14 were
      significantly increased in patients with brucellosis compared with those in
      healthy controls (P < 0.001). Re-analysis of serum samples after treatment in 25
      patients demonstrated that treatment did not result in any significant decline in
      sCD14 levels. Despite a limited study population, these findings may implicate
      CD14 signaling as an important component of the initial anti-brucellar host
      response and suggest that activation of mononuclear phagocytic system is
      sustained even following effective treatment.

PMID- 15728984
TI  - Prevalence of hepatitis B infection in the southeastern region of Turkey:
      comparison of risk factors for HBV infection in rural and urban areas.
AB  - Although hepatitis B has been well studied, there are still aspects of its
      epidemiology that remain to be clarified. There are many regions with high
      seroprevalence, particularly in the developing regions of the world, and these
      regions are known to have different epidemiologic patterns. Nonetheless, there
      are currently no data on the differences in hepatitis B seroprevalence between
      urban and rural areas of Turkey. In the present study, therefore, we used 30
      cluster sampling to determine and compare the prevalence of hepatitis B in the
      urban and rural areas of the least developed region of Turkey, the southeastern
      region. From 2,888 adults living in the region, blood samples were obtained from
      house visits, and screened for HBsAg, anti-HBs, and anti-HBcIgG. Factors
      associated with hepatitis B seroprevalence, particularly living in rural areas,
      were analyzed with multivariate methods. The seroprevalence of HBsAg was 8.2% in
      the rural and 6.2% in the urban areas. There was a statistically significant
      difference between urban and rural regions in terms of HBsAg positivity (crude
      OR: 0.74; 95% CI: 0.55 - 0.98). Exposure to hepatitis B virus (HBV) increased
      with age both in urban and rural areas. Lower education level was also an
      important risk factor for hepatitis B seropositivity in urban areas (adjusted OR:
      1.66; 95% CI: 1.26 - 2.19) but not in rural ones (adjusted OR: 0.77; 95% CI: 0.36
      - 1.69). Familial jaundice history was a statistically significant risk factor
      for HBsAg positivity in rural areas (adjusted OR: 2.15; 95% CI: 1.30 - 3.56) but
      not in urban ones (adjusted OR: 1.48; 95% CI: 0.96 - 2.27). This study shows that
      the prevalence of HBV infection in the southeastern region of Turkey is
      intermediate among the levels reported for the European region of the World
      Health Organization.

PMID- 15728985
TI  - Pneumococcal infections in Trinidad: patterns of antimicrobial susceptibility:
      1994-2002.
AB  - Antimicrobial susceptibilities of 156 Streptococcus pneumoniae strains isolated
      from 1994 through 2002 were studied. Of this total, 38.7, 26.3, 16.7, 8.9, and
      9.6% were recovered from patients with bacteremia, pneumonia, otitis media,
      sinusitis, and meningitis, respectively. All S. pneumoniae strains were fully
      susceptible to amoxicillin-clavulanic acid and ampicillin, with 9.0 and 2.6%
      being resistant to penicillin and ceftriaxone, respectively. The ratios of
      resistant strains to tetracycline, co-trimoxazole, and chloramphenicol were 73.7,
      69.3, and 63.5%, respectively. Approximately 90% of strains remain sensitive to
      erythromycin. A high prevalence of resistance to the penicillins and
      cephalosporins does not exist in Trinidad, although a trend toward such a pattern
      appears to be developing. The most frequent serotype was 14 (38.0%), followed by
      6B (20%), 23F (10.3%), and 4 (6.4%), and all were recovered from children. The
      other serotypes accounted for <6% of the total isolates. All penicillin- and
      ceftriaxone-resistant strains belonged to serotype 14 (MIC > or = 2 microg/ml and
      > or = 4 microg/ml), respectively. Identifiable risk factors for resistant
      isolates included the prevalence of otitis media and sinusitis among children
      treated inadequately with oral cephalosporins; the ease of obtaining antibiotics
      without a prescription at many pharmacies; and the indiscriminate prescribing of
      antibiotics by general practitioners.

PMID- 15728986
TI  - Polymorphisms of the HLA-B and HLA-DRB1 genes in Thai malaria patients.
AB  - The high degree of polymorphism of human leukocyte antigen (HLA) genes has been
      suggested to result from natural selection against susceptibility to a variety of
      infectious pathogens, including malaria. HLA molecules are considered to play a
      crucial role in the defense of the host against malarial infection, and different
      HLA class I and class II alleles have been reported to be associated with reduced
      susceptibility to malaria or the severity of malaria in different populations. To
      test for associations between HLA alleles and the severity of malaria in a Thai
      population, polymorphisms of HLA-B and HLA-DRB1 genes were investigated in 472
      adult patients in northwest Thailand with Plasmodium falciparum malaria. In this
      study, malaria patients were classified into three groups: mild malaria, non
      cerebral severe malaria, and cerebral malaria. Our results revealed that the
      allele frequencies of HLA-B46, -B56, and -DRB1*1001 were statistically different
      between non-cerebral severe malaria and cerebral malaria (P = 0.005), between
      mild malaria and cerebral malaria (P = 0.032), and between mild malaria and non
      cerebral malaria (P = 0.007). However, our results may be showing false positives
      due to multiple testing. Thus, further study with a larger sample size must be
      conducted to obtain conclusive evidence of the association of these HLA-B and
      DRB1 alleles with the severity of malaria in Thailand.

PMID- 15728987
TI  - Salmonella typhi septic arthritis of hip--a case report.
AB  - A case of rarely encountered Salmonella Typhi septic arthritis of the hip in a
      child with no preexisting disease is reported. Salmonella etiology was not
      suspected in this case, and the diagnosis was made only after bacterial
      isolation. Arthrotomy was done as an initial mode of management, followed by
      intravenous ciprofloxacin therapy to which the child responded favorably.

PMID- 15728988
TI  - Interaction of Yersinia enterocolitica biotype 1A strains of diverse origin with
      cultured cells in vitro.
AB  - Yersinia enterocolitica biotype 1A isolates are increasingly being associated
      with diarrhea. However, the mechanism of their pathogenicity is not well
      understood. In the present study interaction of Y. enterocolitica isolates with
      CHO cells, HEp-2 cells and J774 mouse macrophages was studied. Y. enterocolitica
      biotype 1A strains of clinical origin invaded CHO and HEp-2 cells to a
      significantly higher degree than non-clinical isolates. However, among non
      clinical isolates, Y. enterocolitica strains of swine origin showed significantly
      more invasion in CHO and HEp-2 cells than water isolates. Y. enterocolitica
      isolates from clinical samples exhibited a greater level of survival in
      macrophages than isolates from non-clinical sources. It may be construed that Y.
      enterocolitica biotype 1A isolates of clinical and swine origin have higher
      virulence potential than those from other sources.

PMID- 15728989
TI  - Biliary infection and bacteremia caused by beta-lactamase-positive, ampicillin
      resistant Haemophilus influenzae in a diabetic patient.
AB  - We report the case of a 73-year-old female patient with diabetic nephropathy and
      cholelithiasis. She was admitted to our hospital with right upper abdominal pain,
      nausea, and vomiting. The patient had visited an outpatient clinic with the same
      complaints 2 days earlier, and had been prescribed antibiotics empirically (two
      doses ofloxacin orally). Blood cultures taken before the start of antibiotic
      treatment in our hospital were negative. The patient was treated with parenteral
      ampicillin/sulbactam + ciprofloxacin empirically. The empiric antibiotic
      treatment was discontinued after 7 days. Elective cholecystectomy was performed
      after her general condition improved. An aerobic chocolate agar culture of the
      cholecystectomy material yielded Haemophilus influenzae type b. On postoperative
      day 3 the patient developed fever again. The fluids collected after
      cholecystectomy were evaluated microbiologically. H. influenzae type b was
      isolated from the samples and blood cultures. The patient was diagnosed with H.
      influenzae cholecystitis, and recovered after 10-day treatment with
      ampicillin/sulbactam + ciprofloxacin. The findings are discussed together with
      references for differential diagnosis. H. influenzae cholecystitis due to
      cholelithiasis, although rare, should be considered in elderly patients with a
      history of chronic diseases such as diabetes mellitus or nephropathy.

PMID- 15728990
TI  - New rapid screen for the detection of imipenem-resistant Acinetobacter baumanii.
AB  - A rapid screen was developed for the detection of imipenem-resistant
      Acinetobacter baumanii (IRAb) following a recent outbreak in the Surgical
      Intensive Care Unit (SICU) of a hospital in Singapore. Antimicrobial solutions of
      imipenem ranging from 16 mg/L to 64 mg/L were prepared in-house. Each of the
      antimicrobial solutions was then incorporated singularly into MacConkey agar
      plates by two different methods. One of the methods involved preparing MacConkey
      agar plates in-house and then adding the antimicrobial solution before the agar
      solidified (AS method). In the second method, 1 ml of the antimicrobial solution
      was poured onto the surface of the agar plate (LAS method). Fifty hand-nutrient
      broth washes of medical staff working in the SICU, Medical Intensive Care Unit,
      Medical Rehabilitation Ward, and Surgical Rehabilitation Ward were inoculated
      onto the two types of agar media. Two strains of IRAb were isolated from the
      hands. The LAS plates showed faster bacterial growth of resistant pathogens by
      about 24 h, and their detection was easier because susceptible bacteria were
      inhibited by the antimicrobial. The LAS method incorporating imipenem at 32 mg/L
      is recommended for the rapid screening of resistant pathogens in the routine
      clinical laboratory.

PMID- 15728991
TI  - Efficacy of throat gargling for detection of group a beta-hemolytic
      streptococcus.
AB  - The purpose of our study was to investigate the suitability of throat gargling
      with sterile saline as an alternative method to throat swabs for detection of
      group A beta- hemolytic streptococcus (GAS). Throat specimens were obtained from
      601 cases belonging to different age groups. Sterile Dacron swabs and gargle
      residue were first streaked on the side of a 5% sheep blood agar plate to which a
      0.04 U bacitracin disk had been applied, and then 1.25 mg trimethoprim and 23.75
      mg sulphamethoxazole were added to the plate. After incubation, beta-hemolytic
      colonies were classified serologically by latex agglutination. GAS was detected
      in both throat swabs and throat gargle specimens in 49 cases, but GAS was also
      detected in 12 throat swabs from patients with culture-negative gargles and in 8
      gargle specimens from subjects in whom throat swabs were culture negative. The
      strength of agreement was evaluated by calculating the kappa coefficient (K =
      0.82, P = 0.000). The sensitivity, specificity, positive predictive value, and
      negative predictive value of throat gargle specimens were 80.3, 98.5, 85.9, and
      97.8%, respectively. Although the conventional throat swab culture remains the
      gold standard, the throat gargle method is a quick, safe, and easy method for
      detection of GAS that serves as an effective alternative to throat swab culture.

PMID- 15728992
TI  - Chlamydia trachomatis antigen positivity in women in risk groups and its
      relationship with the use of antibiotics.
AB  - The present study examined the use of antibiotics with respect to the rate of
      Chlamydia trachomatis positivity. Our subjects were 282 sexually active Turkish
      females between the ages of 15 and 42. Endocervical samples were investigated in
      60 women with pelvic inflammatory diseases (PIDs), 90 infertile patients (IPs),
      92 registered commercial sex workers (CSWs), and 40 intrauterine device (IUD)
      users. All samples were analyzed using direct immunofluorescence test techniques
      for the presence of C. trachomatis antigen, which was found in 12.7% of our
      subjects, with positive results as high as 26% in patients between 21 and 30
      years of age. C. trachomatis positivity was found to be 16.6% in PID patients,
      and 23.3% in IPs, and 5.4% in CSWs; however, it was not found among IUD users.
      The rate of positivity was highest in IPs; and lowest in registered CSWs (P <
      0.05), who are periodically examined for the presence of sexually transmitted
      diseases, as required by Turkish authorities. Interestingly, the usage of
      therapeutic or prophylactic antibiotics such as tetracycline and ceftriaxon was
      found to be quite high among IUD users (90% use of tetracycline) and CSWs (100%
      use of both antibiotcs). Our results show that C. trachomatis positivity in the
      southeast region of Turkey is not significantly higher than that found in
      previous studies on sex workers of other countries. Additionally, our results
      indicate the use of prophylactic antibiotics decreases the rate of chlamydial
      infections.

PMID- 15728993
TI  - In vitro susceptibility of Candida species isolated from blood culture to some
      antifungal agents.
AB  - Fungal infections are among the major causes of morbidity in cancer patients. In
      order to optimize the treatment of such patients, it is critical to determine the
      type of fungus causing infection as well as its susceptibility to antifungals.
      This study was undertaken to the study resistance of Candida spp. isolated from
      blood cultures of cancer patients to ketoconazole (KET), fluconazole (FLU),
      amphotericin B (AmpB), and flucytosine (FCU). A modified NCCLS M 27-A method was
      used to evaluate the activity of the species. Of the 56 Candida albicans
      isolates, 7 (12.5%) were resistant to FLU (MIC > or = 64 microg/ml), 6 (10.7%)
      were resistant to KET (MIC > or = 64 microg/ml) and 3 (5.3%) were resistant to
      FCU (MIC > or = 32 microg/ml). One (14.3%) of 7 C. parapsilosis isolates was
      resistant to FLU (MIC > or = 64 microg/ml). One (33.3%) of 3 C. tropicalis
      isolates was resistant to KET (MIC > or = 64 microg/ml). None of the C.
      guilliermondii or C. pelliculosa isolates was resistant to KET, FLU, AmpB, or
      FCU. Based on these results, AmpB is an effective antifungal agent that can be
      used against all Candida isolates.

PMID- 15728994
TI  - The resistance to major antituberculous drugs of Mycobacterium tuberculosis
      strains isolated from the respiratory system specimens of tuberculosis patients
      in Duzce, Turkey.
AB  - Through generally curable, tuberculosis (TB) is becoming increasingly resistant
      to commonly used antibiotics. Drug-resistant and multidrug-resistant (MDR)-TB is
      a consequence of monotherapy, insufficient drug therapy and national TB control
      programs. The present study was designed to reveal the resistance to major
      antimicrobial drugs (isoniazid [INH], streptomycin [SM], ethambutol [EMB], and
      rifampicin [RIF]) of Mycobacterium tuberculosis isolated from the respiratory
      specimens of TB patients in Duzce, Turkey. A total of 62 TB patients (46 male, 16
      female; age: 17 - 75 mean: 42 +/- 15.9) were included in the study; 52 (83.8%)
      were new cases and susceptible to all anti-TB drugs, while 10 (16.2%) were
      previously treated cases. Antimicrobial susceptibility tests were performed by
      the proportion method in Lowenstein-Jensen medium. Fifty-two of the 62 (83.8%)
      isolated M. tuberculosis strains were found to be susceptible to all drugs, and 7
      (11.3%), 5 (8%), and 3 (4.8%) were resistant to SM, INH, and RIF, respectively; 3
      (4.8%) were MDR. There were no EMB-resistant strains. The results of this study
      show the presence of drug-resistant and MDR strains of TB at Duzce in the
      northwest part of Turkey.

PMID- 15728995
TI  - Major bacteria of community-acquired respiratory tract infections in Turkey.
AB  - To determine the bacterial etiology of lower respiratory tract infections (LRTIs)
      in Turkey, quantitative cultures of sputum were carried out. The major pathogens
      for LTRIs were found to be Haemophilus influenzae, followed by Streptococcus
      pneumoniae and Moraxella catarrhalis. Only 6.1% of the H. inlfuenzae and all
      strains of M. catarrhalis were beta-lactamase producers. An E-test showed that
      31.2% of the S. pneumoniae strains had an intermediate resistance to penicillin,
      and the remaining strains were susceptible; no fully resistant strains were
      detected.

PMID- 15728996
TI  - Probe typing of noroviruses detected in Osaka City, Japan.

PMID- 15728997
TI  - Outbreak of food poisoning caused by lunch boxes prepared by a company
      contaminated with multidrug resistant Salmonella typhimurium DT104.

PMID- 15728998
TI  - Genotyping of Giardia isolates from humans in Japan using the small subunit
      ribosomal RNA and glutamate dehydrogenase gene sequences.

PMID- 15728999
TI  - Identification of the nonA and nonB loci of Bacillus subtilis Marburg permitting
      the growth of SP10 phage.
AB  - Mutational inactivation of both nonA and nonB genes are required for the
      permissiveness of Bacillus subtilis Marburg cells to infection by phage SP10. By
      transformational analysis of the nonA strain with DNAs from gently lysed
      protoplasts carrying the integrative plasmid pMUTIN (em) insertions in every 20
      kb along the whole chromosome, we have identified the nonA to be the cured state
      of endogenous prophage SPbeta. Direct DNA sequencing, on the other hand, revealed
      one nonsense mutation of nonB in ydiR, which is a component gene of the intrinsic
      restriction system BsuMR of B.subtilis Marburg. Introduction of the wild type
      ydiR into the nonB strain at aprE locus resulted in complementation of nonB.
      Furthermore, as the SP10 genome was found to possess multiple BsuM target sites,
      it is considered that SP10 can infect and multiply in B.subtilis cells, which are
      SPbeta free and possess a defective BsuMR restriction system.

PMID- 15729000
TI  - Construction of unmodified oligonucleotide-based microarrays in the thermophilic
      cyanobacterium Thermosynechococcus elongatus BP-1: screening of the candidates
      for circadianly expressed genes.
AB  - DNA microarrays with unmodified oligonucleotide probes are a cost-effective and
      high-performance alternative to cDNA microarrays. We searched every gene in the
      genome of the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 for
      45-mer oligonucleotide probes with optimal nucleotide sequences, and found such
      probes in 90% of the genes. Using the probes, we constructed a microarray that
      represented 2,397 genes (95% of total genes). We detected only low signals in the
      negative control probes whose nucleotide sequences are not contained in the T.
      elongatus genome, demonstrating that specific hybridization occurred. To evaluate
      the reliability of the measurements obtained by the oligonucleotide microarray,
      we performed microarray experiments using RNA samples from two different time
      points of circadianly synchronized cultures, LL2 (early sub-jective day) and LL14
      (early subjective night). Measurements obtained from the two independent
      microarray hybridizations were highly concordant (correlation coefficient [r] >
      0.8). Northern blot analyses of 20 genes confirmed that expression changes
      detected by the microarrays were correct (r = 0.832). We identified 143 candidate
      clock-controlled genes whose expression levels at LL2 and LL14 were significantly
      different. Expression of 69 of them was enhanced at LL14 while expression of the
      other 74 was enhanced at LL2. The physiological functions of the genes were
      diverse and included metabolism, translation, transcription, membrane transport,
      DNA replication and repair, and cell growth and death.

PMID- 15729001
TI  - Nonconcerted evolution of histone 3 genes in a liverwort, Conocephalum conicum.
AB  - To estimate the extent of genetic variation at the DNA level, the histone 3 (H3)
      genes were sequenced from single individual each from the three cryptic species
      recognized based on allozyme analyses, YFS, J and T types of Conocephalum conicum
      and two closely related species, C. japonicum and Marchantia polymorpha. Although
      the H3 genes are known to be highly conserved, the nucleotide diversities were
      0.128, 0.109, 0.108, 0.049 and 0.034. These values are 30 to 100 times higher
      than that in Drosophila melanogaster (0.001). Besides, there were considerable
      differences in the position, length and number of introns among the loci of H3
      genes. The observed high level of nucleotide diversities was explained by the
      fixation of many random mutations, and non-concerted evolution that resulted from
      low rates of unequal crossing-over and gene conversion probably due to the
      dispersed structure of H3 genes on genome in this species. The non-concerted
      evolutionary pattern was established by the analysis of phylogenetic tree and
      divergence rates. This study confirmed previous results suggesting that natural
      populations of liverwort maintains high extent of variation at DNA level.

PMID- 15729002
TI  - Effect of single alien chromosome from shallot (Allium cepa L. Aggregatum group)
      on carbohydrate production in leaf blade of bunching onion (A. fistulosum L.).
AB  - We used a complete set of Allium fistulosum - shallot (A. cepa Aggregatum group)
      monosomic addition lines (FF+1A - FF+8A) to identify shallot chromosomes
      affecting the production of sugars. In the alien addition lines grown over two
      years in an experimental field at Yamaguchi University (34 degrees N, 131 degrees
      E), shallot chromosomes 2A and 8A altered sugar contents in leaf-bunching onion
      (A. fistulosum). Except for FF+2A, every monosomic addition accumulated non
      reducing sugars in winter leaf blades. FF+8A caused an increase in the amounts of
      non-reducing sugars in the winter. FF+2A hardly produced non-reducing sugar
      throughout the two-year study. These results indicated that genes related to non
      reducing sugar metabolism are located on the 2A and 8A chromosomes. The results
      of regression analyses using 2002 data on A. fistulosum and the monosomic
      addition set revealed a correlation (r = 0.63 +/- 0.07; mean +/- SE., n = 9)
      between reducing sugar and monosaccharide (Glc+Fru) contents but no correlation
      between non-reducing sugar and sucrose contents. This result indicates the
      existence of other polysaccharides (e.g., scorodose) as non-reducing sugars in
      the leaf blade.

PMID- 15729003
TI  - Comparative sequence analysis of a gene-dense region among closely related
      species of Drosophila melanogaster.
AB  - Comparative sequence analysis among closely related species is essential for
      investigating the evolution of non-coding sequences, which evolve more rapidly
      than protein-coding sequences. We sequenced the cytogenetic map 56F10-16, a gene
      dense region of D. simulans and D. sechellia, closely related species to D.
      melanogaster. About 57 kb of the genomic sequences containing 19 genes were
      annotated from each species according to the corresponding region of the D.
      melanogaster genome. The order and orientation of genes were perfectly conserved
      among the three species, and no transposable elements were found. The rate of
      nucleotide substitutions in the non-coding sequences was lower than that at the
      fourfold-degenerate sites, implying functional constraints in the non-coding
      regions. The sequence information from three closely related species, allowed us
      to estimate the insertions and the deletions that may have occurred in the
      lineages of D. simulans and D. sechellia using the D. melanogaster sequence as an
      outgroup. The number of deletions was twice that of insertions for the introns of
      D. simulans. More remarkably, the deletion outnumbered insertions by 7.5 times
      for the intergenic sequences of D. sechellia. These results suggest that the non
      coding sequences have been shortened by deletion biases. However, the deletion
      bias was lower than that previously estimated for pseudogenes, suggesting that
      the non-coding sequences are already rich in functional elements, possibly
      involved in the regulation of gene expression including transcription and pre
      mRNA processing. These features of non-coding sequences may be common to other
      gene-dense regions contributing to the compactness of the Drosophila genome.

PMID- 15729004
TI  - Species-specific accumulation of interspersed sequences in genus Saccharum.
AB  - The genus Saccharum consists of two wild and four cultivated species. Novel
      interspersed sequences were isolated from cultivated sugar cane S. officinarum.
      These sequences were accumulated in all four cultivated species and their wild
      ancestral species S. robustum, but were not detected in the other wild species S.
      spontaneum and the relative Erianthus arundinaceus. The species-specific
      accumulation of interspersed sequences would correlate to the domestication of
      sugar canes.

PMID- 15729005
TI  - "Points to consider" regarding safety assessment of biotechnology-derived
      pharmaceuticals in non-clinical studies (English translation).
AB  - Regulatory and industrial scientists collaborated to publish a "points to
      consider" document regarding the safety assessment of biotechnology-derived
      pharmaceuticals in non-clinical studies in 2002 (Pharmaceutical Non-clinical
      Investigation Group, 2002). The collaboration team intended to clarify the
      interpretation of ICH-S6 guideline and furthermore share recent Japanese
      practices on this matter. However, the document was written in Japanese. Thus, we
      share here an English translation of the document so that non-native Japanese
      correctly understand the contents.

PMID- 15729006
TI  - A further study on the reliability of toxicokinetic parameters for predicting
      hepatotoxicity in rats receiving a 28-day repeated administration of DDT.
AB  - We previously demonstrated a good correlation between the increased relative
      liver weight caused by DDT and the area under the concentration-time curve (AUC)
      of DDT or the total DDT (T-DDT) in plasma and liver of rats in a 7-day repeated
      dose study at 1000 ppm. To confirm the reliability of AUC for predicting toxic
      responses at different dose levels, we conducted a further 28-day repeated dose
      study of p,p'-DDT in male F344 rats at dietary levels of 50, 160, and 500 ppm.
      Concentrations of DDT and its metabolites in plasma, brain, liver, and fat for
      each dose group were measured at various time intervals during the study. The
      concentrations of DDT and T-DDT in plasma and liver were compared with their AUCs
      in relation to hepatotoxic responses including increased relative liver weight,
      microsomal enzyme induction (CYP2B1), and inhibition of gap junctional
      intercellular communication. The coefficient (R(2)) values of each toxic response
      in correlation with AUCs were generally much higher than those with
      concentrations at any dose levels, although the R(2) values vary considerably
      among toxic parameters. These results have confirmed that the AUC of DDT or T-DDT
      in plasma or liver is a reliable marker for predicting hepatotoxicity caused by
      DDT in repeated dose studies.

PMID- 15729007
TI  - Effects of flutamide on sex maturation and behavior of offspring born to female
      rats treated during late pregnancy.
AB  - Flutamide, when administered subcutaneously to female rats at doses of 3, 10, or
      30 mg/kg/day during late pregnancy (gestational days 16-21), significantly and
      dose-dependently decreased anogenital distance (AGD) of the male offspring in
      each dose group compared to controls. Significant delays in preputial separation
      were found in males at a dose of 30 mg/kg, but body weight gain was not
      inhibited. Cryptorchidism and absence of the prostate gland and seminal vesicles
      were found in males at doses > or = 10 mg/kg, and testicular hypoplasia at a dose
      of 30 mg/kg. Hypospadias was noted in all dose groups and vaginal pouches at
      doses of > or =10 mg/kg. The effects on the accessory reproductive organs were
      severe, although the effects on the testes themselves were mild. However, those
      effects appeared to become more pronounced with growth, as evaluated on Days 30
      and 42 and Weeks 16 to 18. Most of these affected animals displayed
      cryptorchidism. Male offspring exposed to flutamide in utero showed impairments
      of sexual behavior as adults in a dose-related manner. Number and frequency of
      mounts with intromissions was markedly decreased in all treated groups as
      compared to controls. At 10 mg/kg, no mounting with ejaculation was observed, and
      at a dose of 30 mg/kg, no mounting with intromission or ejaculation was observed.
      These changes in sexual behavior were closely associated with abnormalities of
      the external genitalia. Animals with hypospadias did not display mounts with
      ejaculation. However, F1 males that copulated at a dose of 3 mg/kg had a normal
      reproductive function. Histological examination of the reproductive organs
      revealed degeneration of the seminiferous tubules, hypospermatogenesis, and
      hypoplasia and inflammation of the seminal vesicles and prostate. Serum levels of
      FSH, LH, and testosterone in these animals were comparable between control and
      all dose groups. Therefore, the male reproductive dysfunction seen in the present
      study could not be attributed to abnormal sex hormone levels during maturation,
      but to possible demasculinization of the brain and progressively delayed
      dysmorphology of the male genitalia caused by fetal exposure to flutamide.

PMID- 15729008
TI  - Revision and establishment of Japanese drinking water quality guidelines for di(2
      ethylhexyl) phthalate, toluene and vinyl chloride -- differences from the latest
      WHO guideline drafts.
AB  - The revision of the Japanese drinking water quality guidelines was established in
      May 2003. The WHO drinking water quality guidelines for the 3(rd) edition were
      also revised and the draft has been open to the public since last year. Most
      guideline values of each chemical in both Japan and WHO were quite similar;
      however, there are different overt values for three chemicals. In this short
      communication, we describe them and discuss the reason for taking the different
      toxicity endpoints and derivation method for these three chemicals, di(2
      ethylhexyl) phthalate, toluene and vinyl chloride.

PMID- 15729010
TI  - Oral single- and repeated-dose toxicity studies on Geranti Bio-Ge Yeast, organic
      germanium fortified yeasts, in dogs.
AB  - Single- and 13-week repeated-dose toxicities of Geranti Bio-Ge Yeast, organic
      germanium fortified yeasts, were investigated in dogs. Both sexes of Beagle dogs
      were orally administered once at a dose of 2,000 mg/kg in single-dose toxicity or
      daily for 13 weeks at doses of 500, 1,000 or 2,000 mg/kg in repeated-dose
      toxicity tests. In single-dose toxicity test, no animal dead, moribund, or
      showing clinical signs or changes in body weight gain was found. In repeated-dose
      toxicity study, there were no considerable changes in ophthalmoscopy and
      urinalysis. Several alterations were observed in electrocardiography, hematology
      and blood biochemistry, including heart rate, R-R interval, QT correcting,
      reticulocytes, activated partial thromboplastin time and albumin/globulin ratio
      in only male dogs, but not in females, administered with Geranti Bio-Ge Yeast in
      a dose-independent manner. In gross findings, several cases of abnormal findings
      were observed in both control and treatment groups, showing diffuse dark brown to
      black discoloration of liver, in a dose-independent manner. In microscopic
      examination, mild lesions, including cholestasis and inflammatory cell foci in
      liver, kidneys and prostate, were found sporadically in both control and
      treatment groups. In spite of some alterations in electrocardiography,
      hematology, blood biochemistry, gross and microscopic findings, such effects were
      not considered to include toxicopathological significance, based on the marginal
      changes within normal ranges and lack of dose-dependency, consistent time-course
      and gender relationship. Taken together, it is suggested that no observed adverse
      effect level (NOAEL) of Geranti Bio-Ge Yeast is considered to be 2,000 mg/kg in
      dogs, and that long-term treatment in clinical trials might not exert adverse
      effects.

PMID- 15729009
TI  - Oral single- and repeated-dose toxicity studies on Geranti Bio-Ge yeast, organic
      germanium fortified yeasts, in rats.
AB  - Single- and 13-week repeated-dose toxicities of Geranti Bio-Ge Yeast, organic
      germanium fortified yeasts, were investigated in rats. Both sexes of Sprague
      Dawley rats were orally administered once at a dose of 2,000 mg/kg in single-dose
      toxicity or daily for 13 weeks at doses of 500, 1,000 or 2,000 mg/kg in repeated
      dose toxicity tests. In single-dose toxicity test to determine dose levels in
      repeated-dose toxicity study, the body weight gain was suppressed at 2,000 mg/kg,
      although no death, clinical signs and pathological findings related to the
      treatment were observed. In repeated-dose toxicity test, there were no clinical
      signs in animals administered up to 2,000 mg/kg, except one rat died due to a
      gavage error. In addition, no significant changes in feed consumption and body
      weight gain were obtained during the treatment period, in spite of week-to-week
      fluctuation of water consumption. There were no considerable changes in
      ophthalmoscopy, urinalysis, hematology and serum biochemistry, except a
      significant decrease in albumin/globulin ratio in males treated with 1,000 mg/kg.
      In contrast, a significant increase in relative heart weight was observed in both
      male and female rats treated with a high dose (2,000 mg/kg) of Geranti Bio-Ge
      Yeast. In microscopic examination, mild lesions were found sporadically in both
      control and treatment groups in a dose-independent manner. In spite of some
      alterations in water consumption, serum biochemistry and organ weights, such
      effects were not considered to include toxicopathological significance, based on
      the lack of dose-dependency, consistent time-course and gender relationship.
      Taken together, it is suggested that no observed adverse effect level (NOAEL) of
      Geranti Bio-Ge Yeast is considered to be over 2,000 mg/kg in rats, and that long
      term oral intake in humans might not exert adverse effects.

PMID- 15729011
TI  - Immigration, HIV infection, and antiretroviral therapy in Italy. An
      epidemiological and clinical survey.
AB  - Epidemiological, clinical, and therapeutic features of 77 consecutive HIV
      infected non-European Union immigrants were compared according to gender.
      Immigrants (from Sub-Saharan Africa in around 60% of cases) represented 7.9% of
      our patient cohort at the end of 2002. Compared with male patients, females were
      more numerous, significantly younger (p.0001), and experienced sexual exposure
      versus drug addiction (p.02), while no difference was observed according to place
      of origin. A negative HIV serology preceding immigration was available for five
      women and four males only, while HIV disease was known before migration in 14 men
      versus 7 women (p.04). The tendency towards a shorter known history of HIV
      infection (p.05) of females versus males may be responsible for a lower incidence
      of AIDS among women (p.02). The use of antiretroviral treatment was matched by
      time and selected regimens, but compliance proved significantly greater in
      females versus males (p.0001), and women had less need of a regimen switch due to
      poor tolerability or refusal (73.2% versus 61.1%); the latter could be
      responsible for a greater mean CD4+ count (p.02), and lower mean plasma viremia
      (p.0001), although no difference was found when considering viral suppression
      rate (70.7% among women, 52.8% among men). Surveillance studies and prospective
      therapeutic trials are strongly warranted, in order to have a reliable assessment
      of HIV-infected immigrated people, to check the efficacy of preventive measures,
      obtain validated data about the clinical, virologic, and immunological evolution
      and outcome of HIV infection undergoing HAART, and to evaluate the frequency and
      role of eventual untoward effects of pharmacologic treatment.

PMID- 15729012
TI  - Stenotrophomonas maltophilia lipopolysaccharide (LPS) and antibiotics: "in vitro"
      effects on inflammatory mediators.
AB  - Stenotrophomonas maltophilia is an emerging pathogen implicated in an increasing
      number of severe pulmonary infections and nosocomial sepsis. We evaluated the
      influence of four different antibiotics on the bacterial count and LPS activity
      found in broth cultures of S. maltophilia. After 4 h ceftazidime (CTZ) decreased
      live bacteria but increased endotoxin activity, whilst isepamicin (ISE),
      tobramycin (TB), and polymyxin B (PB) reduced both of them. We also investigated
      the influence of the above mentioned antibiotics on the ability of S. maltophilia
      culture filtrates and S. maltophilia LPS, extracted in our laboratory, to
      stimulate sepsis mediators such as tumor necrosis factor a (TNF-a), interleukin 8
      (IL-8), interleukin 10 (IL-10), Nitric Oxide (NO) and as
      bactericidal/permeability-increasing protein (BPI) in human whole blood. Our
      results demonstrated that both single polycationic antibiotics and the
      combination of two molecules are able to kill bacteria and neutralize released S.
      maltophilia LPS. Combination between beta-lactams and aminoglycosides is often
      able to reduce the pro-inflammatory effects of S. maltophilia culture filtrates.

PMID- 15729013
TI  - [Campylobacter enteritis in Western Sicily. Remarks on 35 cases].
AB  - INTRODUCTION: Campylobacter spp is the main cause of bacterial gastroenteritis in
      the developed countries, resulting mainly from the contamination of poultry and
      animal products. Pathogenesis remains unclear. Various clinical features ranging
      from watery diarrhoea in apyrexia to dysentery in hyperpyrexia may be the result
      of differences between strains in the expression of different pathogenetic
      factors. There are many difficulties in isolating the bacteria in question.
      METHODS: We processed 540 faecal specimens of children with gastroenteritis. We
      detected enteropathogen bacteria including Campylobacter spp as well as
      Rotavirus, Adenovirus and protozoans. For the isolation of Campylobacter we
      employed the filter membrane technique. The filtrate was plated onto non
      selective agar (blood-agar) in microaerophilic atmosphere. RESULTS: The rank
      order of isolation frequency was: Rotavirus (30.0%), Salmonella (18.5%),
      Adenovirus (12.6%), Campylobacter (6.5%), Shigella (1.1%), Giardia (0.6%). The
      Campylobacter strains belonged to C.jejuni in 31 cases and C. coli in 4 cases.
      The clinical features were: fever (80%), vomitus (31,4%) and diarrhoea in all
      cases (watery diarrhoea (25.7%), stools more compact with mucus and blood (57.1%)
      or with mucus alone (17.1%)). CONCLUSIONS: In Western Sicily Campylobacter spp is
      the second most common agent of bacterial enteritis. We believe that some
      procedural errors, such as the employment of excessively selective media, could
      be the cause of the past failure to isolate Campylobacter.

PMID- 15729014
TI  - [Epidemiology of tuberculosis in immigrant patients hospitalised in Infectious
      Diseases Units in Italy: multicentric study].
AB  - In order to retrospectively evaluate the prevalence of immigrant patients
      affected by active tuberculosis, we analysed the clinical data of 2255 immigrant
      patients hospitalised during 2002 in ordinary admission or in Day Hospital in 48
      Clinics of Infectious Diseases. In all, 303 patients were affected by active
      tuberculosis (13.4% of the total immigrant hospitalised patients); 30 patients
      (9.9%) were also HIV-positive. There was a considerable male gender bias (62.5%);
      the mean age was 29.7 years; 144 patients were from Africa (47.5%), 72 (23.7%)
      from Asia, 47 (15.5%) from eastern Europe and 40 (13.2%) from South America. The
      clinical variants were: pulmonary (57.7%), lymph node (15.8%), meningitis
      (13.8%), intestinal (4.2%), bone (3.3%), pleurical (2.3%), peritoneal (2.3%) and
      renal (0.6%). We conclude that tuberculosis is a very frequent disease among
      immigrants, especially of African origin. The high percentage is due to several
      factors, such as no vaccine prophylaxis and poor, overcrowded living conditions.
      It is fundamental to focus on the need to provide better health support for all
      subjects by setting up screening plans to estimate the real incidence of this
      pathology and ensure medical treatment to prevent the spread of this infection
      among immigrants and the local host population.

PMID- 15729015
TI  - [Streptococcus pneumoniae meningitis in children. Case records 1985 - 2003].
AB  - Acute bacterial meningitis and sepsis are the most severe among invasive diseases
      due to Streptococcus pneumoniae, particularly in pediatric age, and present a
      high risk of mortality and neurologic sequelae. S. pneumoniae is a major
      worldwide pathogen in children. The widespread emergence of penicillin-resistant
      pneumococci, a new pneumococcal conjugate vaccine, and the epidemiological
      prevalence of some serotypes, have recently focused attention on S. pneumoniae
      disease. We reviewed the data on incidence, epidemiology, diagnosis, therapy in
      children hospitalized with acute bacterial meningitis in the Division of
      Infectious Diseases of the Bambino Gesu Children's Hospital, Rome, between 1985-
      2003. S. pneumoniae was isolated in 16.3% of the children, progressively emerging
      as the prevalent pathogen. The highest incidence was found in children younger
      than 2 yrs. The disease still presents a high rate of long-term sequelae,
      especially hearing loss and neurological handicap. Penicillin and ampicillin
      resistant isolates were found in 2.3% of positive cultures; no strain was
      resistant to cephalosporins and vancomycin. Our data support the recommendations
      to consider administration of the 7-valent pneumococcal conjugate vaccine for
      children older than 2 months of age, with special consideration for selected
      groups. We recommend monitoring all invasive pneumococcal infections in children,
      the emergence of antibiotic-resistance and changes in prevalence of pathogen
      serotypes.

PMID- 15729017
TI  - [A case of diphyllobothriasis: description and diagnosis].
AB  - We describe a case of asymptomatic infection caused by Diphyllobothrium latum,
      probably following a meal of "sushi" in a Japanese restaurant in Rome one year
      before. The diagnosis was obtained observing morphology and seizures of
      proglottids and ova. We recall the life cycle of this cestode and report criteria
      for a differential diagnosis with other species of the Diphyllobothrium genus,
      usually rare in humans, and caused by the ingestion of marine fish and not
      freshwater fish.

PMID- 15729016
TI  - [Clinical efficacy and tolerability of short course therapy with cefaclor
      compared with long-term therapy for treatment of acute otitis media in children].
AB  - Clinical efficacy and tolerability of two different regimens of cefaclor were
      studied in 410 paediatric patients affected by non-recurrent acute otitis media
      (AOM). 204 patients were randomly treated with cefaclor given at the dosage of 50
      mg/kg/die in two doses for 5 days; 206 patients with 40 mg/kg/die in two doses
      for 10 days. Diagnosis of acute otitis media was based on the following signs and
      symptoms: otalgia, fever, possible otorrhea, alterations of tympanic membrane
      under otoscopic examination. At the end of the treatment 95.5% of patients were
      cured after short-term therapy and 94.8% after long-term therapy. At the follow
      up (two months after the interruption of treatment) 19 and 17 patients
      respectively had a recurrence. Side effects were observed in 6.9% and 8.7% of
      patients respectively (not statistically significant); they were mild, never
      requiring interruption of the treatment. Cefaclor therapy is very effective for
      treating children aged 2-6 years affected by acute otitis media, with no
      significant difference related to treatment duration. Short-course treatments
      appear better in terms of compliance and tolerability.

PMID- 15729018
TI  - Nosocomial Aspergillus flavus wound infections following cardiac surgery.
AB  - In this report we describe three cases of Aspergillus flavus sternal wound
      infection following cardiac surgery. All three cases occurred in a 3-month period
      coinciding with hospital renovation activities. The patients were successfully
      treated with combined surgical and medical therapy.

PMID- 15729019
TI  - [Hepatitis-associated aplastic anemia: description of a new case].
AB  - Hepatitis-associated aplastic anemia is an only recently recognised syndrome. We
      present a case whereby a month after an episode of fever, a 17-year-old boy was
      recovered with liver enzyme elevation and circulating platelet reduction. All the
      acute viral hepatitis markers were negative. After bone marrow aspiration a
      severe aplastic anemia was diagnosed and all the findings were consistent with
      hepatitis-associated aplastic anemia. The disorder was initially treated with
      glucocorticoids and platelet transfusion, obtaining the normalization of the
      liver enzymes but worsening of the aplastic anemia. An HLA-identical related
      marrow donor was not found. The patient responded to immunosuppressive treatment
      but died of multi-organ failure due to severe sepsis.

PMID- 15729020
TI  - Paranasal sinus mucormycosis in an immunocompetent host: efficacy and safety of
      combination therapy with Liposomal Amphotericin B and adjuvant rHuGM-CSF.
AB  - Invasive mucormycosis is a well-documented disease in the immunocompromised
      patient, but in recent years it has been reported increasingly in immunocompetent
      patients. We report a case of maxillary paranasal sinus mucormycosis in an
      immunologically competent host that was successfully treated with surgery and
      combined liposomal amphotericin B and rHuGM-CSF. We discuss the emerging
      incidence of invasive zygomycosis in immunocompetent patients and the potential
      clinical application of immunotherapy as adjunctive therapy for invasive
      mucormycosis in association with liposomal amphotericin B and surgical
      debridement.

PMID- 15729021
TI  - [Historical insights into tuberculosis. Girolamo Fracastoro's intuition on the
      transmission of tuberculosis and his opponents. History of an idea].
AB  - The author presents the ideas of Girolamo Fracastoro, an Italian scientist from
      Verona, who postulated in 1546 that tuberculosis was caused by "seminaria
      contagionum", which were invisible but somehow living and transmissible, that
      harboured a fondness for those who were constitutionally receptive. This was
      followed by a major discussion, but the official scientific world did not
      understand the real importance of the revolutionary idea. Nevertheless, during
      the 17th and 18th centuries in Italy, but also in France and Spain, the first
      measures to reduce the spread of tubercular disease were adopted. These public
      health measures were extended with some difficulty, but were mostly abandoned at
      the end of 18th century, before the beginning and the development of microbiology
      as a science. The author presents the more successful guidelines against
      tuberculosis proposed at that time.

PMID- 15729022
TI  - Making it safer.

PMID- 15729038
TI  - The state of the science: focus on work environments.

PMID- 15729023
TI  - PTSD in nurses.

PMID- 15729039
TI  - Tsunami report: bigger than oneself.

PMID- 15729041
TI  - Nutrition in older adults.
AB  - Both physiologic and psychosocial changes affect the nutritional status of adults
      over the age of 65. Malnutrition is, in fact, a greater threat to this population
      than obesity. This article reviews the intake requirements of older adults and
      discusses the risk factors that can lead to malnutrition, including diet, limited
      income, isolation, chronic illness, and physiologic changes. Assessment and
      nursing interventions are also addressed.

PMID- 15729043
TI  - Psoriasis in the war zone.

PMID- 15729045
TI  - Enteral tube flushing.

PMID- 15729047
TI  - Body art and MRI.

PMID- 15729049
TI  - Emergency preparedness for the chronically ill.

PMID- 15729053
TI  - Executive summary: the State of the Science on Safe Medication Administration
      symposium.

PMID- 15729054
TI  - A brave new world.

PMID- 15729057
TI  - Return and report.

PMID- 15729060
TI  - An aggressive surgical approach leads to improved survival in patients with
      gallbladder cancer: a 12-year study at a North American Center.
AB  - OBJECTIVE: To determine if an aggressive surgical approach, with an increase in
      R0 resections, has resulted in improved survival for patients with gallbladder
      cancer. SUMMARY BACKGROUND DATA: Many physicians express a relatively nihilistic
      approach to the treatment of gallbladder cancer; consensus among surgeons
      regarding the indications for a radical surgical approach has not been reached.
      METHODS: A retrospective review of all patients with gallbladder cancer admitted
      during the past 12 years was conducted. Ninety-nine patients were identified.
      Cases treated during the 12-year period 1990 to 2002 were divided into 2 time
      period (TP) cohorts, those treated in the first 6 years (TP1, N = 35) and those
      treated in the last 6 years (TP2, N = 64). RESULTS: Disease stratification by
      stage and other demographic features were similar in the 2 time periods. An
      operation with curative intent was performed on 38 patients. Nine (26%) R0
      resections were performed in TP1 and 24 (38%) in TP2. The number of liver
      resections, as well as the frequency of extrahepatic biliary resections, was
      greater in TP2 (P < 0.04). In both time periods, an R0 resection was associated
      with improved survival (P < 0.02 TP1, P < 0.0001 TP2). Overall survival of all
      patients in TP2 was significantly greater than in TP1 (P < 0.03), with a median
      survival of 9 months in TP1 and 17 months in TP2. The median 5-year survival in
      TP1 was 7%, and 35% in TP2. The surgical mortality rate for the entire cohort was
      2%, with a 49% morbidity rate. CONCLUSIONS: A margin-negative, R0 resection leads
      to improved survival in patients with gallbladder cancer.

PMID- 15729061
TI  - Gallbladder cancer: what is an aggressive approach?

PMID- 15729062
TI  - A systematic review of strategies to improve prophylaxis for venous
      thromboembolism in hospitals.
AB  - OBJECTIVE: To assess the effectiveness of different strategies for increasing the
      uptake of prophylaxis for venous thromboembolism (VTE) in hospitalized patients
      through a systematic review of the literature. METHODS: Literature databases and
      the Internet were searched from 1996 to May 2003. Studies of strategies to
      improve VTE prophylaxis practice were included. Studies where no policy or
      guideline was implemented or where the focus of the study was not VTE prevention
      were excluded. RESULTS: Thirty studies were included. The quality of the
      available evidence was average with the majority of studies being uncontrolled
      before and after design and thus limited by the historical nature of much of the
      available data. Adherence to guidelines and the provision of adequate prophylaxis
      were poor in studies which relied on passive dissemination of guidelines. In
      general, the use of multiple strategies was more effective than a single strategy
      used in isolation. The most effective strategies incorporated a system for
      reminding clinicians to assess patients for VTE risk, either electronic decision
      support systems or paper-based reminders, and used audit and feedback to
      facilitate the iterative refinement of the intervention. There were no studies
      adequately powered to demonstrate a reduction in rates of VTE. Insufficient
      evidence was available to make useful comparisons of strategies in terms of costs
      and resource utilization. CONCLUSIONS: Passive dissemination of guidelines is
      unlikely to improve VTE prophylaxis practice. A number of active strategies used
      together, which incorporate some method for reminding clinicians to assess
      patients for DVT risk and assisting the selection of appropriate prophylaxis, are
      likely to result in the achievement of optimal outcomes.

PMID- 15729063
TI  - Functional recovery after open versus laparoscopic colonic resection: a
      randomized, blinded study.
AB  - BACKGROUND: Laparoscopic colonic surgery has been claimed to hasten recovery and
      reduce hospital stay compared with open operation. Recently, enforced multimodal
      rehabilitation (fast-track surgery) has improved recovery and reduced hospital
      stay in both laparoscopic and open colonic surgery. Since no comparative data
      between laparoscopic and open colonic resection with multimodal rehabilitation
      are available, the value of laparoscopy per se is unknown. METHODS: In a
      randomized, observer-and-patient, blinded trial, 60 patients (median age 75
      years) underwent elective laparoscopic or open colonic resection with fast-track
      rehabilitation and planned discharge after 48 hours. Functional recovery was
      assessed in detail during the first postoperative month. RESULTS: Median
      postoperative hospital stay was 2 days in both groups, with early and similar
      recovery to normal activities as assessed by hours of mobilization per day,
      computerized monitoring of motor activity assessed, pulmonary function,
      cardiovascular response to treadmill exercise, pain, sleep quality, fatigue, and
      return to normal gastrointestinal function. There were no significant differences
      in postoperative morbidity, mortality, or readmissions, although 3 patients died
      in the open versus nil in the laparoscopic group. CONCLUSION: Functional recovery
      after colonic resection is rapid with a multimodal rehabilitation regimen and
      without differences between open and laparoscopic operation. Further large-scale
      studies are required on potential differences in serious morbidity and mortality.

PMID- 15729064
TI  - Survival benefit in critically ill burned patients receiving selective
      decontamination of the digestive tract: a randomized, placebo-controlled, double
      blind trial.
AB  - OBJECTIVE: To evaluate whether selective digestive decontamination (SDD) reduces
      mortality from any cause, and the incidence of pneumonia among patients with
      severe burns. SUMMARY BACKGROUND DATA: SDD is a prophylactic strategy to reduce
      infectious morbidity and mortality in critically ill patients. Two meta-analyses
      and a recent randomized controlled trial demonstrated a mortality reduction
      varying between 20% and 40%. But this technique has never been properly evaluated
      in severely burned patients. METHODS: The design of this single-center trial was
      randomized, double blind, placebo controlled. Patients with burns > or =20% of
      total body surface and/or suspected inhalation injury were enrolled and assigned
      to receive SDD or placebo for the total duration of treatment in the burn
      intensive care unit (ICU). RESULTS: One hundred seventeen patients were
      randomized and 107 were analyzed (53 in the SDD group and 54 in the placebo
      group). The ICU mortality was 27.8% in the placebo group and 9.4% in the SDD
      group in the burn ICU. Treatment with SDD was associated with a significant
      reduction in mortality both in the burn ICU (risk ratio 0.25; 95% CI 0.08 to
      0.76) and in the hospital (risk ratio 0.28; 95% CI 0.10 to 0.80), following
      adjustment for predicted mortality. The incidence of pneumonia was significantly
      higher in the placebo group: 30.8 and 17.0 pneumonias per 1000 ventilation days
      (P = 0.03) in placebo and SDD group, respectively. CONCLUSIONS: Treatment with
      SDD reduces mortality and pneumonia incidence in patients with severe burns.

PMID- 15729066
TI  - A prospective randomized study to test the transfer of basic psychomotor skills
      from virtual reality to physical reality in a comparable training setting.
AB  - OBJECTIVE: To test whether basic skills acquired on a virtual endoscopic surgery
      simulator are transferable from virtual reality to physical reality in a
      comparable training setting. SUMMARY BACKGROUND DATA: For surgical training in
      laparoscopic surgery, new training methods have to be developed that allow
      surgeons to first practice in a simulated setting before operating on real
      patients. A virtual endoscopic surgery trainer (VEST) has been developed within
      the framework of a joint project. Because of principal limitations of simulation
      techniques, it is essential to know whether training with this simulator is
      comparable to conventional training. METHODS: Devices used were the VEST system
      and a conventional video trainer (CVT). Two basic training tasks were constructed
      identically (a) as virtual tasks and (b) as mechanical models for the CVT. Test
      persons were divided into 2 groups each consisting of 12 novices and 4 experts.
      Each group carried out a defined training program over the course of 4
      consecutive days on the VEST or the CVT, respectively. To test the transfer of
      skills, the groups switched devices on the 5th day. The main parameter was task
      completion time. RESULTS: The novices in both groups showed similar learning
      curves. The mean task completion times decreased significantly over the 4
      training days of the study. The task completion times for the control task on Day
      5 were significantly lower than on Days 1 and 2. The experts' task completion
      times were much lower than those of the novices. CONCLUSIONS: This study showed
      that training with a computer simulator, just as with the CVT, resulted in a
      reproducible training effect. The control task showed that skills learned in
      virtual reality are transferable to the physical reality of a CVT. The fact that
      the experts showed little improvement demonstrates that the simulation trains
      surgeons in basic laparoscopic skills learned in years of practice.

PMID- 15729065
TI  - Effect of intermittent pneumatic compression of foot and calf on walking
      distance, hemodynamics, and quality of life in patients with arterial
      claudication: a prospective randomized controlled study with 1-year follow-up.
AB  - SUMMARY BACKGROUND DATA: Perioperative mortality, graft failure, and angioplasty
      limitations militate against active intervention for claudication. With the
      exception of exercise programs, conservative treatments yield modest results.
      Intermittent pneumatic compression [IPC] of the foot used daily for 3 months
      enhances the walking ability and pressure indices of claudicants. Although IPC
      applied to the foot and calf together [IPCfoot+calf] is hemodynamically superior
      to IPC of the foot, its clinical effects in claudicants remain undetermined.
      OBJECTIVE: This prospective randomized controlled study evaluates the effects of
      IPCfoot+calf on the walking ability, peripheral hemodynamics, and quality of life
      [QOL] in patients with arterial claudication. METHODS: Forty-one stable
      claudicants, meeting stringent inclusion and exclusion criteria, were randomized
      to receive either IPCfoot+calf and aspirin[75 mg] (Group 1; n = 20), or
      aspirin[75 mg] alone (Group 2; n = 21), with stratification for diabetes and
      smoking. Groups matched for age, sex, initial [ICD] and absolute [ACD]
      claudication distances, pressure indices [ABI], popliteal artery flow, and QOL
      with the short-form 36 Health Survey Questionnaire (SF-36). IPCfoot+calf (120 mm
      Hg, inflation 4 seconds x 3 impulses per minute, calf inflate delay 1 second) was
      used for 5 months, > or =2.5 hours daily. Both groups were advised to exercise
      unsupervised. Evaluation of patients, after randomization, included the ICD and
      ACD, ABI, popliteal artery flow with duplex and QOL* at baseline*, 1/12, 2/12,
      3/12, 4/12, 5/12* and 17/12. Logbooks allowed compliance control. Wilcoxon and
      Mann-Whitney corrected[Bonferroni] tests were used. RESULTS: At 5/12 median ICD,
      ACD, resting and postexercise ABI had increased by 197%, 212%, 17%, and 64%,
      respectively, in Group 1 (P < 0.001), but had changed little (P > 0.1) in Group
      2; Group 1 had better ICD, ACD, and resting and postexercise ABI (P < 0.01) than
      Group 2. Inter- and intragroup popliteal flow differences at 5/12 were small (P >
      0.1). QOL had improved significantly in Group 1 but not in Group 2; QOL in the
      former was better (P < 0.01) than in Group 2. QOL in Group 1 was better (P <
      0.01) than in Group 2 at 5/12. IPC was complication free. IPC compliance (> or
      =2.5 hours/d) was >82% at 1 month and >85% at 3 and 5 months. ABI and walking
      benefits in Group 1 were maintained a year after cessation of IPC treatment.
      CONCLUSIONS: IPCfoot+calf emerged as an effective, high-compliance, complication
      free method for improving the walking ability and pressure indices in stable
      claudication, with a durable outcome. These changes were associated with a
      significant improvement in all aspects of QOL evaluated with the SF-36. Despite
      some limited benefit noted in some individuals, unsupervised exercise had a
      nonsignificant impact overall.

PMID- 15729067
TI  - Evaluating meta-analyses in the general surgical literature: a critical
      appraisal.
AB  - OBJECTIVE: To assess the methodologic quality of meta-analyses of general surgery
      topics published in peer-reviewed journals. SUMMARY BACKGROUND DATA: Systematic
      reviews and meta-analysis are used to seek, summarize, and interpret primary
      studies on a given topic. Accordingly, systematic reviews and meta-analyses of
      high-quality primary studies may be the highest level of evidence for issues of
      prevention and treatment in evidence-based medicine. However, not all published
      meta-analyses are rigorously performed. METHODS: We searched MEDLINE (from
      January 1, 1997, to September 1, 2002) and reference lists and solicited general
      surgery specialists to identify relevant meta-analyses. Inclusion criteria were
      use of meta-analytic methods to pool the results of primary studies in general
      surgery on issues of diagnosis, causation, prognosis, or treatment. Our search
      strategies identified 487 potentially relevant articles. After excluding articles
      based on a priori criteria, 51 meta-analyses fulfilled eligibility criteria. In
      duplicate and independently, 2 reviewers assessed the quality of these meta
      analyses using a 10-item index called the Overview Quality Assessment
      Questionnaire. RESULTS: Overall concordance between 2 independent reviewers was
      good (interobserver agreement 81%, and a kappa of 0.62 (95% CI 0.55-0.69). Of 51
      relevant articles, 38 were published in surgical journals. Most studies had major
      methodologic flaws (median score of 3.3, scale of 1-7). Factors associated with
      low overall scientific quality included the absence of any prior meta-analyses
      publications by authors and meta-analyses produced by surgical department members
      without external collaboration. CONCLUSIONS: This critical appraisal of meta
      analyses published in the general surgery literature demonstrates frequent
      methodologic flaws. The quality of these reports limits the validity of the
      findings and the inferences that can be made about the primary studies reviewed.
      To improve the quality of future meta-analyses, we recommend following guidelines
      for the optimal conduct and reporting of meta-analyses in general surgery.

PMID- 15729068
TI  - Establishment of the world's first telerobotic remote surgical service: for
      provision of advanced laparoscopic surgery in a rural community.
AB  - OBJECTIVE: To establish a telerobotic surgical service between a teaching
      hospital and a rural hospital for provision of telerobotic surgery and assistance
      to aid rural surgeons in providing a variety of advanced laparoscopic surgery to
      their community patients. SUMMARY BACKGROUND DATA: The above service was
      established between St. Joseph's Hospital in Hamilton and North Bay General
      Hospital 400 km north of Hamilton on February 28, 2003. The service uses an IP
      VPN (15 Mbps of bandwidth) commercially available network to connect the robotic
      console in Hamilton with 3 arms of the Zeus-TS surgical system in North Bay.
      RESULTS: To date, 21 telerobotic laparoscopic surgeries have taken place between
      North Bay and Hamilton, including 13 fundoplications, 3 sigmoid resections, 2
      right hemicolectomies, 1 anterior resection, and 2 inguinal hernia repairs. The 2
      surgeons were able to operate together using the same surgical footprint and
      interchange roles seamlessly when desired. There have been no serious
      intraoperative complications and no cases have had to be converted to open
      surgeries. The mean hospital stays were equivalent to mean laparoscopic LOS in
      the tertiary institution. CONCLUSIONS: Telerobotic remote surgery is now in
      routine use, providing high-quality laparoscopic surgical services to patients in
      a rural community and providing a superior degree of collaboration between
      surgeons in teaching hospitals and rural hospitals. Further refinement of the
      robotic and telecommunication technology should ensure its wider application in
      the near future.

PMID- 15729069
TI  - Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal
      rule.
AB  - OBJECTIVE: To assess oncologic outcome of patients treated by conservative
      radical surgery for tumors below 5 cm from the anal verge. SUMMARY BACKGROUND
      DATA: Standard surgical treatment of low rectal cancer below 5 cm from the anal
      verge is abdominoperineal resection. METHODS: From 1990 to 2003, patients with a
      nonfixed rectal carcinoma at 4.5 cm or less from the anal verge and without
      external sphincter infiltration underwent conservative surgery. Surgery included
      total mesorectal excision with intersphincteric resection, that is, removal of
      the internal sphincter, to achieve adequate distal margin. Patients with T3
      disease or internal sphincter infiltration received preoperative radiotherapy.
      RESULTS: Ninety-two patients with a tumor at 3 (range 1.5-4.5) cm from the anal
      verge underwent conservative surgery. There was no mortality and morbidity was
      27%. The rate of complete microscopic resection (R0) was 89%, with 98% negative
      distal margin and 89% negative circumferential margin. In 58 patients with a
      follow-up of more than 24 months, the rate of local recurrence was 2% and the 5
      year overall and disease-free survival were 81% and 70%, respectively.
      CONCLUSIONS: The technique of intersphincteric resection permits us to achieve
      conservative surgery in patients with a tumor close to or in the anal canal
      without compromising local control and survival. Tumor distance from the anal
      verge is no longer a limit for sphincter-saving resection.

PMID- 15729070
TI  - Mild hypothermia provides significant protection against ischemia/reperfusion
      injury in livers of obese and lean rats.
AB  - OBJECTIVE: To evaluate the effect of anesthesia induced mild systemic hypothermia
      on hepatic injury in lean and obese rats during warm ischemia. SUMMARY BACKGROUND
      DATA: Hepatic warm ischemia during surgery remains a significant problem,
      particularly in organs with presumed baseline dysfunction. METHODS: The left and
      median lobes of male lean and obese Zucker rats were exposed to 75 minutes of
      ischemia under either mild hypothermic or normothermic conditions. After 75
      minutes of ischemia, the organs were reperfused and animals were observed for 24
      hours. Surviving animals were killed and blood and tissue was harvested to
      determine liver enzymes and examine the histology. RESULTS: Mild hypothermia
      significantly decreased hepatocellular injury in both lean and obese rats.
      Biochemical markers of hepatic injury were significantly reduced in hypothermic
      groups (P < 0.01). Survival in normo- and hypothermic lean groups were not
      different at 24 hours of reperfusion. However, hypothermia profoundly increased
      survival in obese rats when compared with normothermic obese rats (100% versus
      20%, P < 0.01). Necrosis was more pronounced in both normothermic lean and obese
      animals who experienced more than >75% necrosis when compared with hypothermic
      animals. In contrast, mild hypothermia reduced necrosis in lean rats to less than
      25% and in obese rats to less than 50%. CONCLUSIONS: We demonstrated in a
      clinically relevant model that mild hypothermia significantly reduces hepatic
      injury in a warm ischemia model in lean and obese rats and significantly improved
      24-hour survival in obese rats.

PMID- 15729072
TI  - An appraisal of surgical and percutaneous drainage for pyogenic liver abscesses
      larger than 5 cm.
AB  - OBJECTIVE: To determine whether first-line treatment with percutaneous or
      surgical drainage of liver abscesses larger than 5 cm results in better clinical
      outcome. SUMMARY BACKGROUND DATA: Pyogenic liver abscesses larger than 5 cm are
      currently treated by intravenous antibiotics and either percutaneous (PD) or
      surgical drainage (SD). Percutaneous techniques have been increasingly performed
      in place of open drainage as first-line treatment. This paradigm shift has been
      fueled by the drive for low-risk and less-invasive procedures and the surgical
      option being reserved for percutaneous failures. Yet there is a lack of data to
      support percutaneous drainage over open surgical drainage as first-line
      treatment. METHODS: Over a 3-year period, 80 patients with liver abscesses larger
      than 5 cm amenable to PD and SD were included in the study. This situation was
      possible as 1 team of surgeons favored the use of PD and 1 team favored the use
      of SD as first-line treatment. The treatment outcomes in both groups were
      compared, and clinical end-points included time to defervescence of fever,
      failure of treatment, secondary procedures, hospital stay, morbidity, and
      mortality. RESULTS: PD was performed in 36 patients and SD in 44 patients as
      first-line treatment. Clinical, laboratory, and abscess parameters were
      comparable in both groups. Sixty-four of 80 patients (80%) had multiloculated
      abscess. The time to defervescence of fever was not statistically significant (PD
      versus SD, 4.85 versus 4.38 days; P = 0.09). However, SD had less treatment
      failures (3 versus 10, P = 0.013), less requirement for secondary procedures (5
      versus 13, P = 0.01), and shorter length of hospital stay (8 versus 11 days, P =
      0.03). There was no difference in morbidity or mortality rates. CONCLUSIONS: The
      results of our study show that for large liver abscesses more than 5 cm, SD
      provides better clinical outcomes than PD in terms of treatment success, number
      of secondary procedures, and hospital stay with comparable morbidity and
      mortality rates. SD should be considered as first-line treatment of large liver
      abscesses.

PMID- 15729071
TI  - Ischemic preconditioning impairs liver regeneration in extended reduced-size
      livers.
AB  - OBJECTIVE: To evaluate the effect of ischemic preconditioning (IPC) in an
      experimental setting of extended liver resection with 30 minutes of inflow
      occlusion in rats. SUMMARY BACKGROUND DATA: IPC has been proven an effective
      strategy against hepatic ischemia-reperfusion injury in both animal and human
      studies. However, decreased protective effects in terms of transaminase levels
      were found in patients with larger resection volume, questioning the benefit of
      IPC in case of small liver remnants. METHODS: Rats undergoing 90% hepatectomy
      under strict inflow occlusion for 30 minutes were subjected to either receive or
      not receive an IPC period (5 minutes of ischemia followed by 30 minutes of
      reperfusion). In addition to 10-day survival rate, laser Doppler flowmetry of
      hepatic blood flow and fluorescence microscopic analysis of the hepatic
      microcirculation were performed to assess the effect of IPC on initial
      microvascular reperfusion of liver remnants after 90% resection. Moreover,
      regeneration capacity of livers undergoing IPC and 70% resection was studied over
      7 days by means of histology and immunohistochemistry. RESULTS: Ten-day survival
      of rats which underwent IPC and 90% hepatectomy was 0 out of 10 animals versus 1
      out of 10 animals without IPC. Hemodynamic and microcirculatory analysis revealed
      signs of hyperperfusion during initial reperfusion of preconditioned liver
      remnants in 90% hepatectomized animals. In addition to increased transaminase
      levels, IPC impaired hepatic proliferative response after 70% organ resection, as
      indicated by both a significant reduction in mitotic figures and Ki-67 nuclear
      staining of hepatocytes, as well as a decrease in restitution of liver mass.
      CONCLUSIONS: Though portal hypertension reflecting shear stress has been reported
      to trigger liver regeneration, remnant liver tissue after major hepatectomy may
      not benefit from hyperperfusion-induced trigger for cell cycle entry but is
      rather dominated from hyperperfusion-induced local organ injury. Further studies
      are required to finally judge on the harmfulness of IPC in extended liver
      resection.

PMID- 15729073
TI  - CEACAM6 is a novel biomarker in pancreatic adenocarcinoma and PanIN lesions.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that CEACAM6
      expression is an indicator of adverse pathologic features and clinical outcome in
      pancreatic adenocarcinoma. SUMMARY BACKGROUND DATA: Previously, we have
      demonstrated carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6)
      to be an oncoprotein that plays an important role in the biology of pancreatic
      adenocarcinoma. Suppression of CEACAM6 expression reduces tumorigenesis and
      metastasis in vivo. METHODS: A tissue microarray was constructed using tumor
      specimens obtained from 89 consecutive patients who had undergone pancreatic
      resection for pancreatic adenocarcinoma with curative intent. A second microarray
      containing 54 pancreatic intraepithelial neoplasia (PanIN) lesions was
      constructed using tissues from a separate cohort of 44 patients. Both arrays were
      immunostained using a specific anti-CEACAM6 monoclonal antibody. Tumoral CEACAM6
      expression was dichotomized into negative and positive immunoreactivity groups.
      The log-rank test was used to evaluate univariate associations of CEACAM6
      expression with prognosis. Survival curves were derived using the Kaplan-Meier
      method. RESULTS: Tumoral CEACAM6 expression was detected in 82 (92%) pancreatic
      adenocarcinoma specimens. CEACAM6 expression was more prevalent in high-grade
      than in low-grade PanIN lesions (P = 0.0002). Negative tumoral CEACAM6 expression
      was associated with absence of lymph node metastases (P = 0.012), lower disease
      stage (P = 0.008), and longer postoperative survival (P = 0.047). CONCLUSIONS:
      CEACAM6 is a novel biomarker for pancreatic adenocarcinoma. CEACAM6 warrants
      further evaluation as both a prognostic factor and a therapeutic target in
      pancreatic cancer.

PMID- 15729074
TI  - Prolongation of cardiac allograft survival by systemic administration of immature
      recipient dendritic cells deficient in NF-kappaB activity.
AB  - OBJECTIVE: To develop a more applicable approach that uses recipient-derived
      dendritic cells (DC) for organ transplantation. SUMMARY BACKGROUND DATA: Systemic
      administration of immature donor DC that are deficient in costimulatory molecules
      delays the onset of allograft rejection. However, this approach requires in vitro
      DC propagation and would not be applicable to deceased donor organ
      transplantation. METHODS: DC were propagated from C3H (H2) mouse bone marrow with
      GM-CSF; their maturation was arrested by treatment with oligodeoxyribonucleotides
      (ODN) specifically against nuclear factor (NF)-kappaB. The DC were pulsed with
      B10 (H2) splenocyte lysate. DC phenotype was examined by flow cytometry. Their
      allostimulatory activity was assessed in vitro by MLR and CTL assays and in vivo
      by the influence on B10 cardiac allograft survival. Cytokine profiles were
      analyzed by ELISA and RNase protection assay. NF-kappaB activity in DC nuclear
      protein was detected by gel shifting assay. RESULTS: Compared with mature DC, NF
      kappaB ODN-treated immature DC pulsed with B10 (H2) spleen cell lysate elicited
      markedly lower proliferative responses and correlated with reduced IFN-gamma and
      increased IL-10 production. In contrast to administration of mature C3H DC pulsed
      with B10 antigen that accelerated rejection of B10 cardiac allografts, a single
      injection of NF-kappaB ODN DC pulsed with donor antigens significantly prolonged
      allograft survival in an antigen-specific manner. This was associated with
      induction of T-cell hyporesponsiveness and enhanced T-cell apoptosis.
      CONCLUSIONS: An approach to use recipient DC as a "vaccine" strategy provides a
      more feasible approach for deceased-donor organ transplantation.

PMID- 15729075
TI  - Small-diameter blood vessels engineered with bone marrow-derived cells.
AB  - OBJECTIVE: The objective of this study is to investigate if bone marrow-derived
      cells (BMCs) regenerate vascular tissues and improve patency in tissue-engineered
      small-diameter (internal diameter = 3 mm) vascular grafts. SUMMARY BACKGROUND
      DATA: BMCs have demonstrated the ability to differentiate into endothelial-like
      cells and vascular smooth muscle-like cells and may offer an alternative cell
      source for vascular tissue engineering. Thus, we tissue-engineered small-diameter
      vascular grafts with BMCs and decellularized arteries. METHODS: Canine BMCs were
      differentiated in vitro into smooth muscle alpha-actin/smooth muscle myosin heavy
      chain-positive cells and von Willebrand factor/CD31-positive cells and seeded
      onto decellularized canine carotid arteries (internal diameter = 3 mm). The
      seeded grafts were implanted in cell donor dogs. The vascular-tissue regeneration
      and graft patency were investigated with immunohistochemistry and angiography,
      respectively. RESULTS: The vascular grafts seeded with BMCs remained patent for
      up to 8 weeks in the canine carotid artery interposition model, whereas nonseeded
      grafts occluded within 2 weeks. Within 8 weeks after implantation, the vascular
      grafts showed regeneration of the 3 elements of artery (endothelium, media, and
      adventitia). BMCs labeled with a fluorescent dye prior to implantation were
      detected in the retrieved vascular grafts, indicating that the BMCs participated
      in the vascular tissue regeneration. CONCLUSIONS: Here we show that BMCs have the
      potential to regenerate vascular tissues and improve patency in tissue-engineered
      small-diameter vascular grafts. This is the first report of a small-diameter
      neovessel engineered with BMCs as a cell source.

PMID- 15729076
TI  - Clinical implications for the management of acute thromboembolic occlusion of the
      superior mesenteric artery: autopsy findings in 213 patients.
AB  - OBJECTIVE: To study findings at autopsy in patients with fatal acute
      thromboembolic occlusion of the superior mesenteric artery (SMA). SUMMARY
      BACKGROUND DATA: Acute occlusion of the SMA is difficult to diagnose and
      mortality remains high. In Malmo, Sweden, the autopsy rate between 1970 and 1982
      was 87%, creating possibilities for a population-based study. METHODS: Among
      23,496 clinical autopsies and 7569 forensic autopsies, 213 cases with acute
      thromboembolic occlusion of the SMA and intestinal infarction were identified.
      RESULTS: A clinical suspicion of intestinal infarction was documented in 32% of
      the patients, only 35% being in the care of surgeons. The embolus/thrombus ratio
      was 1.4 to 1. Thrombotic occlusions were located more proximally than embolic
      occlusions (P < 0.001), intestinal infarction was more extensive (P = 0.025) and
      thrombotic occlusions were associated with old brain infarction (P = 0.048),
      aortic wall thrombosis (P = 0.080), and disseminated cancer (P = 0.079). Patients
      with embolic occlusions (n = 122) had a higher frequency of acute myocardial
      infarction (AMI) than patients with thrombotic occlusions (P = 0.049). The
      embolic source was identified in 80%. In 115 (94%), synchronous embolism and/or
      source of embolus were present. There were findings of remaining cardiac thrombi
      in 58 (48%) and synchronous emboli affected 273 other arterial segments in 83
      (68%). CONCLUSIONS: Early recognition and revascularization would have been a
      prerequisite for survival in at least half of the patients, since the jejunum,
      ileum, and colon were affected by infarction. A minority of all patients were
      under surgical care. AMI, cardiac thrombi, and synchronous emboli were common
      findings among patients with embolic occlusions.

PMID- 15729077
TI  - Blue rubber bleb nevus syndrome: surgical eradication of gastrointestinal
      bleeding.
AB  - OBJECTIVE: We report the largest clinical experience to date of surgically
      treated patients with blue rubber bleb nevus syndrome (BRBNS). SUMMARY BACKGROUND
      DATA: BRBNS is a rare congenital disorder presenting with multifocal venous
      malformations of the skin, soft tissues, and gastrointestinal (GI) tract.
      Patients with BRBNS develop anemia from chronic GI bleeding, and require lifelong
      treatment with iron and blood transfusions. An aggressive surgical approach to
      treat the GI venous malformations of BRBNS has been considered unlikely to be
      successful because of the large number of lesions, their position throughout the
      GI tract, and the likelihood of recurrence. Based on our belief that eradicated
      lesions would not recur, we undertook the removal of all GI tract lesions in an
      effort to eliminate bleeding. METHODS: Ten patients with BRBNS were treated from
      1993 to 2002. Lesions were identified using complete GI endoscopy. The multiple
      venous malformations were removed by a combination of wedge resection,
      polypectomy, suture-ligation, segmental bowel resection, and band ligation.
      RESULTS: Patient ages ranged from 2 to 36 years, and patients received an average
      of 53 prior blood transfusions. A mean of 137 focal GI venous malformations per
      patient were resected at operation (range 4-557), with a mean operative duration
      of 14 hours (range 7-23 hours). Only 1 patient who had a less extensive procedure
      developed recurrent GI bleeding. The mean follow-up period was 5.0 years (range
      2.9-10.3 years). CONCLUSIONS: We believe that an aggressive excisional approach
      is indicated for the venous anomalies that cause GI bleeding in BRBNS.

PMID- 15729078
TI  - Meckel diverticulum: the Mayo Clinic experience with 1476 patients (1950-2002).
AB  - OBJECTIVE: Through a comprehensive review of the Mayo Clinic experience with
      patients who had Meckel diverticulum, we sought to determine which diverticula
      should be removed when discovered incidentally during abdominal surgery. SUMMARY
      BACKGROUND DATA: Meckel diverticula occur so infrequently that most articles have
      reported either small series or isolated cases. From these limited series,
      various conclusions have been reported without clearly indicating which
      incidental diverticula should be removed. METHODS: Medical records were reviewed
      of 1476 patients found to have a Meckel diverticulum during surgery from 1950 to
      2002. Preoperative diagnosis; age; sex; date of surgery; and intraoperative,
      macroscopic, and microscopic findings from operative and pathology reports were
      recorded. Logistic regression analysis was used to determine which clinical or
      histologic features were associated with symptomatic Meckel diverticulum. The
      features analyzed were age; sex; length, base width, and ratio of length to base
      width of the diverticulum; and the presence of ectopic tissue or abnormal tissue
      (inflammation or enteroliths). RESULTS: Among the 1476 patients, 16% of the
      Meckel diverticula were symptomatic. The most common clinical presentation in
      adults was bleeding; in children, obstruction. Among patients with a symptomatic
      Meckel diverticulum, the male-female ratio was approximately 3:1. Clinical or
      histologic features most commonly associated with symptomatic Meckel diverticula
      were patient age younger than 50 years (odds ratio [OR], 3.5; 95% confidence
      interval [CI], 2.6-4.8; P < 0.001), male sex (OR, 1.8; 95% CI, 1.3-2.4; P <
      0.001); diverticulum length greater than 2 cm (OR, 2.2; 95% CI, 1.1-4.4; P =
      0.02), and the presence of histologically abnormal tissue (OR, 13.9; 95% CI, 9.9
      19.6; P < 0.001). CONCLUSIONS: After analyzing our data, we neither support nor
      reject the recommendation that all Meckel diverticula found incidentally should
      be removed, although the procedure today has little risk. If a selective approach
      is taken, we recommend removing all incidental Meckel diverticula that have any
      of the 4 features most commonly associated with symptomatic Meckel diverticulum.

PMID- 15729080
TI  - Discontinuation rates for selective serotonin reuptake inhibitors and other
      second-generation antidepressants in outpatients with major depressive disorder:
      a systematic review and meta-analysis.
AB  - The present study aimed to systematically compare overall loss to follow-up,
      discontinuation rates because of adverse events and discontinuation rates because
      of a lack of efficacy in published studies assessing the efficacy and
      tolerability of selective serotonin reuptake inhibitors (SSRIs) compared to other
      second-generation antidepressants in treating outpatients with major depressive
      disorder (MDD). We searched MEDLINE, Embase, The Cochrane Library, PsychLit and
      the International Pharmaceutical Abstracts from 1980 to 2004 (April). Twenty
      double-blinded, randomized controlled trials met our eligibility criteria and
      compared SSRIs to other second-generation antidepressants in adult outpatients
      with MDD. Pooled relative risks of discontinuation rates because of (i) any
      reason (overall loss to follow-up), (ii) adverse events and (iii) a lack of
      efficacy did not differ substantially between SSRIs as a class and other second
      generation antidepressants. Taking the similar efficacy of second-generation
      antidepressant into account, our findings suggest that clinicians can focus on
      other practically or clinically relevant considerations such as costs,
      differences in side-effect profiles, onset of action or aspects of health-related
      quality of life to tailor a treatment to an individual patient's needs.

PMID- 15729079
TI  - Prevention of intraperitoneal adhesions and abscesses by polysaccharides isolated
      from Phellinus spp in a rat peritonitis model.
AB  - OBJECTIVE: To assess whether polysaccharides isolated from fungi, Phellinus spp,
      could reduce the adhesion and abscess formation in a rat peritonitis model.
      SUMMARY BACKGROUND DATA: Although polysaccharides from Phellinus spp is a well
      known material with antiinflammatory properties, little is known regarding its
      ability to prevent intraperitoneal adhesions. We have assessed the adhesion- and
      abscess-reducing effect of polysaccharides from Phellinus gilvus (PG) and
      Phellinus linteus (PL) in a rat peritonitis model. METHODS: In 60 SD rats,
      experimental peritonitis was induced using the cecal ligation and puncture model
      (CLP). Animals were randomly assigned to 5 groups; ringer lactate solution (RL
      group), polysaccharides from PG and PL (PG and PL group), hyaluronic acid (HA
      group), and carboxymethylcellulose (CMC group). Intraperitoneal adhesions and
      abscesses were noted at 7 day after CLP. RT-PCR assay for urokinase-type
      plasminogen activator (uPA), its cellular receptor (uPAR), tissue-type
      plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and
      tumor necrosis factor (TNF)- alpha was performed to assess the cecal tissue.
      RESULTS: Adhesion formation was significantly reduced in PG, PL, CMC, and HA
      groups (P < 0.001) compared with that in RL group. The incidence of abscesses was
      also significantly reduced in PG and PL groups (P < 0.05) compared with that in
      the RL group. The level of uPA, uPAR, tPA, and TNF-alpha was highly expressed in
      PG and PL group, as compared with the RL group. CONCLUSIONS: We concluded that PG
      and PL had significant adhesion- and abscess-reducing effects and may act by
      modulating fibrinolytic capacity of uPA and/or tPA produced from macrophages in a
      rat peritonitis model.

PMID- 15729081
TI  - Prediction of response to risperidone treatment with respect to plasma
      concencentrations of risperidone, catecholamine metabolites, and polymorphism of
      cytochrome P450 2D6.
AB  - In the present study, we examined the relationships between plasma concentrations
      of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of
      cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also
      investigated the relationships between plasma levels of 3-methoxy-4
      hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to
      risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years)
      who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional
      disorder and brief psychotic disorder, and who were being treated with
      risperidone alone, were evaluated regarding their clinical improvement and
      extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS)
      and Simpson and Angus (SAS), respectively, and plasma levels of cotinine,
      caffeine, MHPG and HVA were analysed by high-performance liquid chromatography.
      The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction.
      There was a positive correlation between plasma levels of risperidone plus 9
      hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS.
      Pretreatment HVA levels in responders were higher than those in nonresponders. In
      addition, there was a negative correlation between changes in HVA levels and
      improvement in PANSS scores. There was no association between plasma levels of
      risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no
      differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements
      and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that
      pretreatment HVA levels and plasma concentrations of active moiety might play a
      part in predicting the clinical response and occurrence of extrapyramidal
      symptoms, respectively, when treating patients with risperidone.

PMID- 15729082
TI  - Risperidone for pre-existing severe tardive dyskinesia: a 48-week prospective
      follow-up study.
AB  - Atypical antipsychotics can alleviate the severity of tardive dyskinesia, but few
      studies have monitored their long-term effects. The present study investigated
      the effect of risperidone on pre-existing severe tardive dyskinesia among 40
      patients with chronic schizophrenia over 48 weeks. The total Abnormal Involuntary
      Movement Scale (AIMS) score decreased in 35 patients (87.5%) and increased in
      three patients (7.5%). At the end of the 48-week trial, the mean total AIMS score
      decreased significantly, from 15.7+/-4.7 (baseline) to 10.6+/-4.4 (P<0.001), with
      a mean risperidone dosage of 3.6+/-1.5 mg/day. Twenty-three patients (57.5%) were
      responders with an average total AIMS score decrease of 8.0+/-2.7. Multiple
      logistic regression analysis controlling for age, gender, duration of illness,
      index hospitalization duration, risperidone dose, anticholinergic concomitant use
      and dystonia score change revealed that a change in the parkinsonism score was
      the most significant factor related to responders (odds ratio 3.476, 95%
      confidence interval 1.173-10.298). A significant improvement observed in tardive
      dyskinesia was noted at week 8, and this improvement persisted until week 48. The
      results show that the effect of risperidone on pre-existing tardive dyskinesia
      may be beneficial.

PMID- 15729084
TI  - Negative attitude towards medication is associated with working memory impairment
      in schizophrenia patients.
AB  - A lack of insight into illness and negative attitudes towards medication are
      common among individuals with schizophrenia and impact clinical outcomes. This
      study aimed to examine the relationships between attitudes towards medication and
      cognitive function in schizophrenia patients. Thirty-five male forensic
      inpatients who were suffering from chronic schizophrenia participated in the
      study. A drug attitude inventory was used to evaluate the attitudes of the
      patients towards medication. Neuropsychological function was assessed with a
      comprehensive battery of tests. Patients with positive attitudes towards
      medication performed significantly better than those with negative attitudes on
      tests of verbal working memory (digit span forwards and backwards), inhibition
      and set shifting (Penn Inhibition test), delayed object memory and overall mental
      status (Mini Mental State Examination). There were no differences in age,
      education, hospitalizations or clinical symptoms between the groups. Our findings
      support an association between negative attitudes towards medication and poor
      cognitive performance, particularly of working memory.

PMID- 15729083
TI  - The relationship between early changes in the HAMD-17 anxiety/somatization factor
      items and treatment outcome among depressed outpatients.
AB  - The 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety/Somatization
      factor includes six items: Anxiety (psychic), Anxiety (somatic), Somatic Symptoms
      (gastrointestinal), Somatic Symptoms (general), Hypochondriasis and Insight. This
      study examines the relationship between early changes (defined as those observed
      between baseline and week 1) in these HAMD-17 Anxiety/Somatization Factor items
      and treatment outcome among major depressive disorder (MDD) patients who
      participated in a study comparing the antidepressant efficacy of a standardized
      extract of hypericum with both placebo and fluoxetine. Following a 1-week, single
      blind washout, patients with MDD diagnosed by the Structured Clinical Interview
      for DSM-IV (SCID) were randomized to 12 weeks of double-blind treatment with
      hypericum extract (900 mg/day), fluoxetine (20 mg/day) or placebo. The
      relationship between early changes in HAMD-17 anxiety/somatization factor items
      and treatment outcome was assessed separately for patients who received study
      treatment (hypericum or fluoxetine) versus placebo with a logistic regression
      method. One hundred and thirty-five patients (female 57%, mean age=37.3+/-11.0
      years; mean baseline HAMD-17=19.7+/-3.2 years) were randomized to double-blind
      treatment and were included in the intent-to-treat (ITT) analyses. After
      adjusting for baseline HAMD-17 scores and for multiple comparisons with the
      Bonferroni correction, patients who remitted (HAMD-17 score <8) after study
      treatment had significantly greater early improvement in Somatic Symptoms
      (General) scores than non-remitters. No other significant differences in early
      changes were noted for the remaining items between remitters versus non-remitters
      who received active treatment. For patients treated with placebo, early change
      was not predictive of remission for any of the items after Bonferroni correction.
      In conclusion, the presence of early improvement on the HAMD-17 item concerning
      fatigue and general somatic symptoms is significantly predictive of achieving
      remission at endpoint with active study treatment but not with placebo.

PMID- 15729085
TI  - Effects of N-PEP-12 on memory among older adults.
AB  - N-PEP-12 is a derivative of cerebrolysin, a brain-derived neuropeptide compound
      that has been approved for the treatment of Alzheimer's disease (AD) in more than
      30 countries. N-PEP-12 is much less potent than cerebrolysin but it can be
      administered orally whereas the parent compound must be administered through
      multiple intravenous infusions. This study was undertaken to determine whether N
      PEP-12 is effective in improving memory and other cognitive abilities among
      healthy older adults who have experienced 'normal' age-related memory loss.
      Subjects were 54 males and females, aged 50 years and older, who presented both
      subjective and objective evidence of memory loss since early adulthood. The study
      was a fully randomized, double-blind comparison of N-PEP-12 and placebo.
      Cognitive assessments were performed at baseline and following 30 days of
      treatment. The primary outcome measure was the Alzheimer's Disease Assessment
      Scale-Cognitive (ADAS-cog) Memory score, with the Syndrom Kurz Test (SKT) test,
      digit cancellation, digit span, verbal fluency and clinical ratings as secondary
      outcomes. N-PEP-12 treated subjects performed better than placebo-treated
      subjects on the ADAS-cog Memory score, the SKT, clinical ratings and some, but
      not other tests. N-PEP-12 may be an effective treatment for memory loss in
      healthy older adults.

PMID- 15729086
TI  - The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on
      olanzapine-induced weight gain in first-episode schizophrenia patients.
AB  - Histamine antagonism has been implicated in antipsychotic drug-induced weight
      gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic
      properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in
      three first-episode schizophrenia patients for 6 weeks. Body weight was measured
      at baseline and weekly thereafter. Clinical rating scales were completed at
      baseline and at week 6. All participants gained weight (mean weight gain 3.1+/
      0.9 kg) and a similar pattern of weight gain was observed: an increase during the
      first 2 weeks and no additional weight gain (two patients) or minor weight loss
      (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the
      cut-off for clinically significant weight gain. Betahistine was safe and well
      tolerated and did not interfere with the antipsychotic effect of olanzapine. Our
      findings justify a placebo-controlled evaluation of the putative weight
      attenuating effect of betahistine in olanzapine-induced weight gain.

PMID- 15729087
TI  - Comparison of the metabolic effects observed in patients treated with ziprasidone
      versus olanzapine.
AB  - This study aimed to examine the impact of ziprasidone and olanzapine on QTc
      interval, weight and metabolic parameters in adults with schizophrenia and other
      psychoses. A retrospective cohort chart review was performed of 191 randomly
      selected patients who were being treated with ziprasidone or olanzapine in an
      integrated health care system. Significant differences on QTc interval were not
      observed. A significant weight gain was observed in olanzapine-treated patients
      (P<0.001) but not in the ziprasidone-treated cohort (P>0.05). Furthermore,
      adverse metabolic changes associated with olanzapine administration were
      significant with respect to effects on total cholesterol (P=0.01), triglycerides
      (P=0.05) and haemoglobin A1C (HbA1C) (P<0.05), whereas significant favourable
      metabolic effects were observed in ziprasidone-treated patients with regard to
      total cholesterol (P<0.05), low-density lipoprotein (LDL) (P<0.01), high-density
      lipoprotein (HDL) (P<0.05) and HbA1c (P<0.05). Our results suggest that these two
      atypical antipsychotics are safe and well tolerated from a cardiovascular
      standpoint, with no differences in QTc interval prolongation being observed.
      Olanzapine-treated patients exhibited significant weight increases, whereas
      ziprasidone-treated patients exhibited weight loss. Olanzapine treatment was also
      associated with significant adverse effect on patient's lipid profile and HbA1c.
      These adverse metabolic effects were not observed in ziprasidone-treated patients
      although favourable effects were observed with regard to effect on total
      cholesterol, LDL, HDL and HbA1c.

PMID- 15729088
TI  - D2-blockade and possible ziprasidone-induced galactorrhea.
AB  - This is the second report of possible ziprasidone-induced galactorrhea in an
      adult female. This case illustrates the need to consider dose as well as potency
      when interpreting the response of a patient to a drug, particularly when the
      response appears to be idiosyncratic.

PMID- 15729089
TI  - Lithium toxicity after switch from fosinopril to lisinopril.
AB  - There is a small body of literature on the interactions between lithium and
      angiotensin-converting enzyme inhibitors (ACEIs), but little data documenting the
      differences between these agents in their impact on serum lithium levels. We
      present the case of a 46-year-old male who sustained a five-fold increase in his
      serum lithium level after switching from fosinopril to lisinopril, with a peak
      serum lithium level of 3.4 meq/l. There was also an increase in serum creatinine
      from 1.1 on fosinopril to 1.4 after switching to lisinopril. The patient was
      hospitalized, and intravenously hydrated with 0.5 normal saline, with a reduction
      of the serum lithium level to 0.7 meq/l by 72 h after admission. The hospital
      course was marked by two episodes of bradycardia, but was otherwise uneventful,
      and the patient was discharged without any neurological sequelae. This case
      demonstrates that ACEIs may have differential effects on renal function, and the
      potential for significant alterations in lithium clearance that may not be
      clinically evident for several weeks. Lithium-treated patients who have a change
      in ACEI, especially those who are older or have below average renal function,
      must have diligent monitoring for the first 4-6 weeks after switching to detect
      potentially serious changes in serum lithium levels.

PMID- 15729090
TI  - Quetiapine-induced myoclonus.
AB  - We report a case of myoclonus induced by quetiapine. A 64-year-old man with
      schizophrenia developed myoclonic jerks when given higher doses of quetiapine.
      These movements were dose-related and completely abated on reducing the dose. To
      our knowledge, these movements have not been reported previously as an adverse
      effect of quetiapine.

PMID- 15729091
TI  - Would discussion on patients' needs add value to the rehabilitation process?
AB  - The objective of this study was to examine the effect of therapists' methods of
      addressing patients' problems (based on assessment results and discussions of
      patients' needs compared with assessment results only) on the level of agreement,
      between patients and therapists, over patients' daily living problems. A
      comparative design was adopted to examine the five most important daily living
      problems identified by patients and their occupational therapists. Twelve
      occupational therapists and five stroke patients of each therapist under in
      patient rehabilitation were recruited. Thus, a total of 60 patients were
      recruited. Content analyses of the therapists' methods of analysing their
      patients' problems revealed that eight therapists had discussed their patients'
      needs with their patients (66.7%) and four relied on the assessment results
      (33.3%). The kappa statistics showed that a higher agreement of daily living
      problems was identified for the patients of those therapists who had held
      discussions (kappa=0.76; P<0.001). The results suggested that therapists should
      take their patients' needs into account in the planning of interventions. If
      therapists could help their patients to carry out their future life roles, it
      would lead the patients to better participate in the rehabilitation process.

PMID- 15729092
TI  - Can the back-to-work rate of patients with long-term non-malignant pain be
      predicted?
AB  - The objective of this study was to evaluate the outcome of a structured
      multidisciplinary rehabilitation programme regarding the return-to-work rate.
      Sixty-seven patients were enrolled in an 8-week, structured rehabilitation
      programme. The prediction of the return-to-work rate was evaluated before
      entering the programme. The patients' own perception of returning to work as well
      as their pain intensity were estimated on a visual analogue scale and their
      period of sick leave was also recorded. The multidisciplinary rehabilitation team
      made an impairment and disability evaluation and analysis (IDEA) to assess
      possible work ability. This evaluation was made during the first 3 weeks of the 8
      week programme. The return-to-work rate was also evaluated by means of the
      modified somatic perception questionnaire (MSPQ) and the disability rating index
      (DRI) before entering the programme. The results were compared with the actual
      return-to-work rate 1 year after completing the programme. A comparison group of
      14 patients who were rejected due to lack of space in the programme was used in
      this study. There was a positive, statistically significant correlation (P<0.01)
      between the evaluation of the multidisciplinary rehabilitation team and the
      actual outcome of the return-to-work rate 1 year after completing the programme.
      At the 1-year follow-up, 63% of the patients had returned to work or were in work
      related activities. The results on MSPQ or DRI, the patients' own perception of
      returning to work, the pain intensity, age or the period of time out of work did
      not predict the return-to-work ability. This study has shown that 63% of the
      patients with long-term non-malignant pain were back to work or in work-related
      activities 1 year after completing the rehabilitation programme. The IDEA made by
      the rehabilitation team was crucial in predicting the return-to-work rate in this
      patient group. The MSPQ and DRI questionnaires, the patients' own prediction,
      pain intensity, age and time out of work had a low value for predicting the
      return-to-work rate following a structured multidisciplinary rehabilitation
      programme.

PMID- 15729093
TI  - Exercise training to improve motor performance in chronic stroke: effects of a
      community-based exercise program.
AB  - The purpose of this study was to investigate the feasibility and efficacy of an
      exercise program offered by a community organization on motor performance in
      individuals with chronic stroke. Twenty hemiparetic individuals at least 6 months
      after a stroke and discharged from all rehabilitation services enrolled in the
      study. They took part in an 8-week group program (two times per week) aimed at
      improving balance, mobility, coordination, walking endurance and strength on the
      hemiparetic side through various functional exercises. Pre- and post-exercise
      assessments included the stroke impairment assessment set, the Berg balance
      scale, the step test, the timed-up-and-go and the 6 min walk. Results showed
      significant improvements (P<0.008) in all of the above tests, excluding the 6 min
      walk, after completion of the exercise training. Correlation analyses revealed
      that the individuals' age and time since injury were poorly related to the
      improvement in performance. It is concluded that an exercise program offered by a
      community organization can lead to improvement in motor performance of
      individuals with chronic stroke. To prevent decline in motor performance,
      community-based exercise programs should thus be made available for stroke
      patients discharged from rehabilitation services.

PMID- 15729094
TI  - Analysis of the results of functional electrical stimulation on hemiplegic
      patients' upper extremities using the Minnesota manual dexterity test.
AB  - To study the influence of functional electric stimulation (FES) on grip
      acquisition and on the change of grip processing speed, 38 hemiplegic patients
      took part in the rehabilitation program of the Division of Rehabilitation
      Medicine of the Hospital das Clinicas, School of Medicine, University of Sao
      Paulo. Half of the patients received FES on their wrist and finger extensor
      muscles. The patients in this study were evaluated initially, then after 3 months
      and after 6 months using the Minnesota manual dexterity test. We concluded that
      the time necessary for use of FES to generate a significant improvement in the
      grip speed in hemiplegic patients is 6 months, using twice-weekly administration
      of stimulation.

PMID- 15729096
TI  - Efficacy of leisure intervention groups and their impact on quality of life among
      people with spinal cord injury.
AB  - Leisure is an important component in the lives of persons with disabilities and
      it is often associated with life satisfaction, self-esteem and depression.
      However, leisure specialists have all but ignored the leisure patterns and needs
      of people with disabilities. Thus this study attempts leisure intervention
      through groups by altering the attitude of patients towards leisure and
      subsequently finding out the effect on leisure satisfaction and quality of life.
      This study was a clinical trial conducted for patients with spinal cord injury
      who were evaluated using both the World Health Organization quality of life scale
      and the leisure satisfaction scale prior to intervention and afterwards. The
      experimental group had five 1 h-long group sessions as intervention while the
      control group had none. Twenty-five clients with paraplegia were included in both
      the experimental and the control groups. The mean ages of clients in both the
      groups were 33.40 and 37.24 years respectively. Significant improvements were
      observed in all domains of quality of life and leisure satisfaction in the
      experimental group as compared with the control group. The data show the definite
      impact of leisure satisfaction on quality of life. It is evident from the study
      that leisure intervention groups facilitate both leisure satisfaction and
      improved quality of life. Such an assertion definitely requires further research,
      corroboration and substantiation.

PMID- 15729095
TI  - Disability pension despite vocational rehabilitation? A study from six social
      insurance offices of a county.
AB  - Many long-term sick-listed individuals move from vocational rehabilitation to
      pension, rather than reaching the goal of return to work. There is thus reason to
      consider whether rehabilitation resources are being used optimally. Individuals
      receiving disability pensions are consuming financial and personnel resources at
      the insurance offices and also consume a large amount of health care. The general
      objective of the study was to evaluate the proportion of individuals granted
      vocational rehabilitation but then obtaining temporary or permanent disability
      pensions. All persons receiving any kind of rehabilitation and attending one of
      six local national insurance offices in a county in Sweden in 1998 and 1999 were
      studied. A 2-year follow-up was carried out to assess changes in status among
      those who had received temporary disability pensions. Of all individuals
      receiving rehabilitation, 46.2% ended up with a disability pension allowance. In
      addition, a large portion of the temporary disability pensions was transformed to
      permanent disability pensions within 2 years. For clients with a temporary
      disability pension, the rate of resuming work was close to nil. Among
      rehabilitation measures, investigation showed the lowest figures of work
      resumption while job training showed the best outcome in this respect. The study
      concluded that a large portion of the financial and personnel resources allocated
      by the national insurance offices to rehabilitation resulted in disability
      pensions.

PMID- 15729097
TI  - Reliability and construct validity studies of an obstacle course assessment of
      wheelchair user performance.
AB  - The objective of this study is to evaluate the reliability and construct validity
      of an obstacle course assessment of wheelchair user performance (OCAWUP).
      Seventeen experienced wheelchair users using three different propulsion methods
      (two hands, one hand and one foot or motorized wheelchair) were assessed twice on
      the 10 obstacles of the OCAWUP. To evaluate reliability, time (in seconds) and
      degree of ease (DE) in overcoming obstacles (four-level scale) were assessed by
      three occupational therapists. Construct validity was assessed by verifying
      whether the OCAWUP's global score of ease (GSE) varied with wheelchair propulsion
      methods and the functional independence measure (FIM). Intraclass correlation
      coefficients calculated for reliability of time and GSE were up to 0.74 for test
      retest reliability and up to 0.97 for interrater reliability. Cohen's kappa
      coefficients calculated for DE reliabilities varied from 0.09 to 1.0 with degrees
      of association up to 65%. A significant difference (P<or =0.01) in GSE scores is
      shown between propulsion methods. A high significant correlation (rs=0.84, P< or
      =0.05) was found between GSE and scores of FIM items associated with mobility.
      Reliability of time and GSE is substantial or better. Reliability of DE is not as
      good, with a few items indicating poor reliability. OCAWUP's construct validity
      is good.

PMID- 15729098
TI  - Characteristics of traumatic spinal cord injuries in south-eastern Anatolia,
      Turkey: a comparative approach to 10 years' experience.
AB  - The purpose of this study was to determine the demographic and epidemiological
      characteristics of traumatic spinal cord-injured patients. The hospital records
      of 539 patients (416 men, 123 women) with spinal cord injuries (SCIs) admitted to
      four hospitals that were major referral centers for trauma in the south-eastern
      region of Turkey from 1990 to 1999 were reviewed retrospectively. The patients
      with SCI were investigated for two periods; the first period covered patients
      admitted between 1990 and 1994 during which time an influx of people from rural
      to urban areas occurred and firearm injuries were common. In the second period
      (1995-1999) the influx of people declined and firearm injuries were reduced. The
      most common causes of injuries were road traffic accidents (200, 37.12%),
      followed by falls (172, 31.90%) and bullet wounds (115, 21.34%). In the first
      period, incomplete paraplegia was encountered more often than in the second
      period (P<0.001). In conclusion, in our series, while the leading cause of SCI
      for the two time periods was road traffic accidents, firearm injuries for the
      first period and falls for the second period were second-most frequent causes of
      SCI. In addition, the present study suggests that demographic and epidemiological
      factors may affect the characteristics of SCI in a region-based population even
      in a 10-year period of time.

PMID- 15729099
TI  - Alternative Web Access toolKit for impairEd users.
AB  - Although navigation through the World Wide Web (WWW) may seem pretty
      straightforward to most of us, a large group of individuals exists for whom it is
      not quite as easy. We are referring to people with disabilities. This paper is a
      proposal for an Internet user agent (browser) designed to help people with severe
      physical impairments to navigate the http://WWW. It utilizes a single switch as
      an input device and scanning as a selection method.

PMID- 15729100
TI  - Assessment of activity of elderly people using a home monitoring system.
AB  - A multisensor home monitoring system has been developed within a telecare project
      to help elderly people by observing mobility changes indicative of abnormal
      events. This paper assesses the motor activity and the relationships between
      activity measures using the system. The motor activity data (in bed, getting up,
      getting out, visiting the toilets) are analysed from a statistical perspective to
      assess changes in occurrence, time and duration. Changes in activity data and
      correlations between in-bed restlessness and getting up variables show
      interesting trends in the behavior of elderly people and can be used by the
      system as a predictive tool in abnormal situations. The objective of the telecare
      project is to build an abnormal event diagnosis system to help elderly people
      living alone.

PMID- 15729101
TI  - Preliminary study to evaluate the validity of the mini-mental state examination
      in a normal population in Turkey.
AB  - Although the Mini-Mental State Examination (MMSE) is widely used in clinical
      practice, normative scores for a healthy population have not been documented in
      Turkey. The aim in this study was to validate the MMSE in a healthy population
      and to provide normal scores. Internal construct validity of the Turkish version
      of MMSE among a preliminary sample of 406 normal people was assessed by Rasch
      unidimensional measurement model. Scores of the normal sample varied according to
      age and education but not according to sex. The data derived from this sample
      showed poor fit to the Rasch model (mean item fit, -2.082, SD 3.022). Only four
      of 11 items met model expectations. There was also differential item functioning
      by education and age for most items. Thus the internal construct validity of the
      Turkish MMSE in a normative sample could not be demonstrated by Rasch analysis.
      The scale failed modern psychometric criteria for scalability. We would therefore
      suggest other large normative MMSE data sets to be tested in terms of internal
      construct validity. If these findings are replicated, the validity of MMSE norms
      and their consequent use in clinical practice should be reconsidered.

PMID- 15729102
TI  - Thoracolumbar corsets alter breathing pattern in normal individuals.
AB  - Thoracolumbar corsets are used to manage stable uncomplicated injuries of the
      spine. The effects of these corsets on breathing pattern either in normal
      individuals or in patients with spinal injuries are not known. This study
      determined the effects of wearing a thoracolumbar corset on breathing patterns.
      Eight healthy, young, non-smoking women students participated by fully informed
      voluntary consent. Selected ventilatory parameters were monitored in supine and
      sitting positions immediately before and after wearing the corset, after wearing
      the corset for 1 h and immediately after removal of the corset. Ventilatory
      variables were monitored by connecting the facemask to the Cortex MetaMax
      (Biophysik GmgH) data collection system. Normalized data were subjected to MANOVA
      (P<0.05). Wearing the corset for 1 h significantly decreased tidal volume (Vt) by
      24% and increased breathing frequency (Fb) by 19% in the sitting compared to the
      control condition. Participants who had been wearing the corset for 1 h had
      significantly lower Vt in the supine position compared to the sitting position.
      We conclude that when a corset is worn for at least 1 h, Vt and Fb change to
      maintain the minute ventilation. More research is indicated to determine the
      effects of wearing a corset for longer than 1 h on pulmonary variables in
      patients.

PMID- 15729103
TI  - Perspectives on disability in Afghanistan and their implications for
      rehabilitation services.
AB  - Twenty years of conflict has severely disrupted the infrastructure and economy of
      Afghanistan. Disability levels are high and much of the population has little
      access to health facilities. Re-establishing and strengthening rehabilitation
      services is therefore an important country priority. The aims of this study were
      to explore perceptions of the nature of disability in Afghanistan and to identify
      implications for the development of rehabilitation services. Over a 4-week
      period, interviews and focus groups, supplemented by field observations, were
      held with a range of service users and other stakeholders (including
      physiotherapist service providers and representatives of the Afghan Disability
      Committee) in the districts of Kabul and Herat. Data analysis identified three
      core themes in discussions with respondents: the nature of disability, causes of
      disability and rehabilitation priorities for people with disability (PWD). Afghan
      society distinguishes between traumatic and congenital disability, but disability
      awareness is much greater for persons with traumatic disability. This group
      enjoys much greater representation in disabled people's organizations. There is a
      strong cultural responsibility to care and provide for PWD rather than to
      encourage independence. Healthcare professionals reflect a medical model in their
      attitudes towards PWD. A key priority of PWD is economic. There is a low
      understanding of rehabilitation practice by PWD and medical staff. Training for
      rehabilitation workers and wider health professionals needs to reflect greater
      emphasis on a social model of disability. Public awareness and enablement of
      people with congenital disability needs to be raised.

PMID- 15729104
TI  - The genetic and environmental basis of the relationship between schizotypy and
      personality: a twin study.
AB  - The clinical phenotype commonly referred to as schizotypy is used in two
      different ways in psychiatric practice. One usage emphasizes psychosis-proneness
      where schizotypy is considered part of the schizophrenia spectrum. The other
      emphasizes personality aberrations and is classed as a personality disorder. The
      present study provides evidence that schizotypy is a unitary construct and that
      features like schizophrenia and personality share a common genetic basis. A
      sample of 102 monozygotic and 90 dizygotic general population twin pairs
      completed measures of psychosis-proneness and traits delineating personality
      disorder. Multivariate genetic analyses showed that the observed relationship
      between psychotic and personality features is caused almost entirely by common
      genetic factors. Environmental factors appear to be unique to each measure. On
      the basis of these findings, it is suggested that the environment mediates change
      in personality function to psychosis as proposed by Meehl's original concept of
      schizotaxia.

PMID- 15729105
TI  - Agreeableness and neuroticism as predictors of relapse after first-episode
      psychosis: a prospective follow-up study.
AB  - Cross-sectional investigations, using the five-factor model of personality have
      evinced relationships among neuroticism, agreeableness, and psychotic symptoms.
      The current study examined these relationships via a prospective follow-up study
      with remitted first-episode psychosis patients. Baseline five-factor model
      personality profiles, diagnoses, symptom ratings, and premorbid adjustment
      ratings were followed by nine monthly ratings on Brief Psychiatric Rating Scale
      psychosis items in 60 first-episode patients. Valid baseline personality profiles
      were completed by 40 patients. Patients who had a return of symptoms scored
      higher on baseline neuroticism and agreeableness than those who remained in
      remission. Premorbid adjustment also predicted return of symptoms. After
      premorbid adjustment was controlled for, the agreeableness differences remained
      significant, but the neuroticism scores were no longer significantly different.
      It is concluded that lower agreeableness acts as a mediating variable in relapse.
      Further studies should clarify whether agreeableness is associated with specific
      biases in processing interpersonal information, and interpersonal behaviors.

PMID- 15729106
TI  - Is the cutoff to define remission on the Hamilton Rating Scale for Depression too
      high?
AB  - The Hamilton Rating Scale for Depression (HRSD) is the most frequently used
      measure of outcome in antidepressant efficacy trials. More than a decade ago, a
      consensus panel recommended that remission be defined on the 17-item version of
      the HRSD as a cutoff <or=7. This recommendation was accompanied by a call for
      research to validate this cutoff value; however, little research in this area has
      been performed since then. The goal of the present study was to compare the
      validity of different HRSD cutoffs for defining remission. Three hundred three
      depressed psychiatric outpatients were rated on the 17-item HRSD, the Global
      Assessment of Functioning (GAF) scale, and the Standardized Clinical Outcome
      Rating for Depression, an index of DSM-IV remission status. We examined the
      sensitivity, specificity, and overall classification rate of the HRSD for
      identifying a broad and narrow interpretation of the DSM-IV definition of
      remission, and the association between the breadth of the definition of remission
      on the HRSD and self-report ratings of global psychosocial functioning and
      quality of life. Based on a narrow definition of DSM-IV remission, which requires
      an absence of clinically significant symptoms of depression, the optimal 17-item
      HRSD cutoff was <or=2. Compared with patients scoring 3 through 7 on the HRSD,
      those who scored 0 to 2 reported significantly less psychosocial impairment and
      better quality of life. Our results thus support the use of a lower cutoff on the
      HRSD than has been traditionally used to define remission.

PMID- 15729107
TI  - Clinical utility of the Defensive Functioning Scale in the assessment of
      depression.
AB  - The Defensive Functioning Scale (DFS) and Overall Defensive Functioning score
      (ODF) have been used as reliable and valid measures of defense structure when
      applied to clinical narratives. This study aims to replicate and extend positive
      clinical validity data for the ODF in the assessment of depression and examine
      the relationship between specific defense levels of the DFS and depressive
      symptoms. Sixty-nine outpatients who completed the Symptom Checklist 90-Revised
      and Personality Assessment Inventory were rated on the DFS by trained clinicians.
      Lower (more maladaptive) scores on the ODF were significantly related to the
      presence and severity of patient-reported depression symptoms. Furthermore,
      depression symptoms were significantly related to both the presence of low-level
      action defenses and an absence of higher-range defenses in the mental inhibitions
      obsessional level. Findings from this study provide further support for the
      clinical application and relevance of the DFS system; support the theory of
      defensive processes falling into a hierarchy of adaptive functioning; and,
      because of a naturalistic setting, are highly generalizable to real-world
      practice.

PMID- 15729108
TI  - Long-term stability of parental representations in depressed outpatients
      utilizing the Parental Bonding Instrument.
AB  - This study addressed two questions: (a) What are the 30-month, 60-month, and 90
      month test-retest reliabilities of the Parental Bonding Instrument (PBI); and (b)
      are recollections of parental bonding stable across changes in the level of
      depressed mood? Participants included 97 outpatients with primary early-onset
      dysthymic disorder and 45 outpatients with episodic major depressive disorder.
      Follow-ups were conducted at 30, 60, and 90 months after entry into the study.
      The PBI was scored using both the original two-factor model and a three-factor
      solution. As indexed by intraclass correlations, stability for the original two
      factor model ranged from .64 to .88, with a median of .77. The intraclass
      correlations for the three-factor model ranged from .54 to .87, with a median of
      .73. The intraclass correlations were generally higher between adjacent
      assessments, but the decrease over increasingly longer intervals was quite small.
      Overall, the results indicated that the PBI is highly stable for intervals as
      long as 90 months. In addition, reports of parental bonding were relatively
      stable despite significant changes in the level of depressed mood. Thus, the
      present study provides evidence for the long-term stability of parental
      representations, as measured by the PBI, in depressed outpatients.

PMID- 15729109
TI  - Functional and work disability in major depressive disorder.
AB  - We examined factors related to social and occupational disability, social
      adjustment, and work disability among patients with major depressive disorder
      (MDD), the dominant mental disorder causing functional and work disability. The
      Vantaa Depression Study comprises a cohort of 269 psychiatric inpatients and
      outpatients with MDD in the city of Vantaa, Finland. Axis I and II diagnoses were
      assessed via semistructured WHO Schedules for Clinical Assessment in
      Neuropsychiatry Version 2.0 and Structured Clinical Interview for DSM-III-R
      personality disorders interviews. Global disability, social and work adjustment,
      and being at work or on sick leave were assessed. The most important factors
      associated with level of social, functional, and work disability were severity
      and recurrence of depression, but older age and current Axis I and II comorbidity
      also significantly contributed. Of those employed, almost half (43%) were on sick
      leave. The most pervasive factors explaining level of functional and work
      disability among patients with MDD were severity and recurrence of depression.
      However, older age and comorbidity also contributed.

PMID- 15729111
TI  - The role of war-zone trauma and PTSD in the etiology of antisocial behavior.
AB  - Historically, successful reintegration of war veterans into civilized society has
      been an enduring concern of nations. Data from the National Vietnam Veterans
      Readjustment Study were used to develop and evaluate an etiological model of
      postwar antisocial behavior. Two initial models specified causal paths among five
      sets of variables, ordered according to their historical occurrence: (a)
      premilitary risk factors, (b) military traumas and disciplinary actions, (c) the
      homecoming reception, (d) postmilitary PTSD and substance abuse, and (e)
      postmilitary antisocial behavior. PTSD and substance abuse were omitted in one
      model and included in the other. The initial models were refined and then cross
      validated, leading to the specification of replicated models with highly
      satisfactory fit and parsimony. Comparison of the two models suggested that (1)
      premilitary experiences and behavior exert the largest effects on postmilitary
      antisocial behavior, and that (2) PTSD plays a necessary mediational role for the
      effects of war-zone traumatic exposure on postmilitary antisocial behavior.

PMID- 15729110
TI  - Quality of life and anxiety disorders: a population study.
AB  - The study of quality of life has increased in importance in the area of mental
      disorders during the last decade. The aim of the present study was to investigate
      the effect of specific anxiety disorders on specific quality of life indicators
      in the common population. More than 2000 individuals between 18 and 65 years old
      were studied by means of structured interviews. The results showed that social
      phobia and panic disorder within the past year and lifetime, and generalized
      anxiety disorder within the past year, had an independent effect on quality of
      life when controlling for a number of sociodemographic variables, somatic health,
      and other DSM-III-R Axis I mental disorders. Specific phobias and obsessive
      compulsive disorder had only a small effect, and agoraphobia showed no effect.
      The effect was strongest for self-realization and contact with friends, but
      anxiety disorders also influenced subjective well-being, social support, negative
      life events, contact with family of origin, and neighborhood quality.

PMID- 15729115
TI  - Thymic hyperplasia in thyroid cancer patients.
AB  - OBJECTIVE: Although there is a well-recognized association between thymic
      hyperplasia and benign thyroid disorders, the prevalence of thymic hyperplasia in
      patients with malignant thyroid diseases has not been previously reported. We
      performed this study to determine the prevalence and morphologic features of
      thymic hyperplasia on CT scans of thyroid cancer patients. CONCLUSIONS: Thymic
      hyperplasia is commonly observed on CT scans of thyroid cancer patients and
      almost always demonstrates a characteristic pyramidal configuration. This
      characteristic appearance should not be mistaken for metastatic disease.

PMID- 15729112
TI  - Computerized content analysis of writings of Mahatma Gandhi.
AB  - Three brief excerpts from the autobiographical writings of Mohandas K. Gandhi
      were analyzed for neuropsychobiological content using the PCAD 2000 computer
      program. The computer software produces scores on 13 scales such as anxiety,
      hostility, cognitive impairment, and depression; compares the assigned scores
      with norms derived from 5-minute speech samples taken from normal, medically and
      psychiatrically healthy adults and children; and suggests DSM-IV diagnostic
      categories for consideration. The results demonstrate an objective, repeatable
      method for achieving insight into the mental states and traits of historic
      figures based on their writings.

PMID- 15729116
TI  - Small incidental pulmonary nodules: how useful is short-term interval CT follow
      up?
AB  - PURPOSE: To determine whether short-term (<6 month) follow-up imaging by thoracic
      CT is necessary to evaluate small (< or =4 mm) noncalcified nodules (NCN) in
      patients with no history of malignancy or acute lung disease. MATERIALS AND
      METHODS: We reviewed serial thoracic helical CT scans between 1999-2000 obtained
      for the evaluation or follow-up imaging of small NCNs. CT scans were performed at
      5-mm collimation. Patients were excluded if they had a history of neoplasm,
      infection, pulmonary fibrosis, or immune deficiency; also excluded if nodule(s) >
      or =5 mm at intake, or no follow-up scan within 1 year. NCNs were evaluated for
      number, size, configuration, and change in size over time. Exact 95% Confidence
      Intervals were used to estimate chances of nodule growth in 3-, 6-, and 12- month
      intervals. RESULTS: A total of 1826 patients received a CT for NCNs. Four hundred
      fourteen patients met inclusion criteria (221 women, 193 men; mean age, 65.6
      years). Eighty-five patients had a single NCN, 329 had multiple NCNs. One hundred
      seventy-three patients had additional > or =5 mm nodules. One hundred twenty
      seven patients were lost to follow up within the 1-year period. Eight nodules
      cleared. None of the < or =4 mm NCNs grew on follow-up imaging within 12 months.
      Three patients developed lung cancer in other nodules > or =5 mm (5-10 mm). These
      nodules grew on follow up intervals of 3-13 months. One patient had a 19 mm
      benign hamartoma that grew in 9 months. The calculated chance that a NCN < or =4
      mm will grow within 3, 6, and 12 months (95% CI) is < or =0.89%, 1.01%, and
      1.28%, respectively. CONCLUSION: The chance of growth in < or =4 mm NCNs in a 3-
      to 6-month period in patients with no previous history of malignancy or immune
      disorder is small; therefore, short-term follow-up imaging (<12 month) for
      nodules < or =4 mm is not necessary.

PMID- 15729117
TI  - Functional cardiac CT and MR: effects of heart rate and software applications on
      measurement validity.
AB  - This study sought to validate different software applications for cardiac
      function analysis using ECG-gated CT and MR datasets in correlation with
      underlying heart rate. Ten patients and a set of ventricular phantoms underwent
      concurrent multislice-CT and cine-MR imaging for evaluation of cardiac function.
      Datasets from both imaging modalities were evaluated utilizing 2 volumetric
      analysis tools to determine left ventricular volume and mass. Initially,
      intraobserver measurement variability was assessed. Detected measurement
      variability was correlated with underlying absolute magnitude of cardiac volumes
      and masses. Subsequently, results were statistically evaluated by determining
      significant data variability depending on imaging modality and choice of
      evaluation software. Finally, the data variability was correlated with underlying
      heart rates. This study showed that all analyzed datasets uniformly presented
      intraobserver variations below 2%, and variability was not related to the
      magnitude of measurement. Significant measurement accuracy was proven in all
      calculated parameters obtained from the cardiac phantoms. Acquired patient
      datasets and calculated functional parameters showed significant data
      homogeneity, with measurement variability coefficients ranging from 0.935-0.955.
      CT datasets showed maximal data variability at heart rates below 60 BpM. MR
      datasets showed maximal data variability at heart rates above 90 BpM. In
      conclusion, CT and MR datasets allowed an interchangeable utilization of
      volumetric analysis tools. However, reliable volumetric analysis was limited to
      an optimal range of cardiac rates for each modality, thus emphasizing the
      necessity of reporting volumetric measurement results in combination with heart
      rate to allow for consideration of this possible cause for measurement variation.

PMID- 15729118
TI  - 3D-multidetector CT angiography in the evaluation of potential donors for living
      donor lung transplantation.
AB  - INTRODUCTION: In living donor lung transplant, donor lobectomies from 2 donors
      provide right and left lower lobes for transplantation. In the past, routine
      evaluation of pulmonary anatomy was not performed preoperatively.
      Intraoperatively, surgeons were often forced to sacrifice the lingular artery or
      right middle lobe segmental artery to obtain an adequate arterial cuff for safe
      reimplantation. This study was performed to evaluate the utility of preoperative
      3D-multidetector CT angiography (3D-MDCTA) as a noninvasive method of assessing
      pulmonary arteries to improve donor selection and surgical planning for living
      lung donors. SUBJECTS AND METHODS: Five potential lung donors for 2 recipients
      were included in the study. CT scanning with 4 channel multidetector-row CT was
      performed, using a modified pulmonary embolism protocol. Post-processing was
      performed using volume rendering techniques on a commercially available
      workstation. RESULTS: 3D-MDCT demonstrated that there are a number of variations
      in pulmonary arterial anatomy and that ideal anatomy was seldom encountered.
      Comparison of different donors determined which lower lobes were most favorable
      for transplantation. Surgery confirmed the accuracy of 3D-MDCTA. There were no
      pulmonary arterial complications, and no vessels were sacrificed. CONCLUSION:
      Safely explanting lower lobes from living donors for lung transplantation poses
      challenges not encountered in harvesting cadaveric donors or performing
      lobectomies for malignancy. 3D-MDCTA of pulmonary arteries can noninvasively
      delineate the often-complex pulmonary anatomy, which may assist in donor
      selection as well as reduce donor intraoperative and postoperative vascular
      complications.

PMID- 15729119
TI  - Diagnosis of subsegmental pulmonary emboli: a multi-center study using a porcine
      model.
AB  - We measured sensitivity, positive predictive value, and free-response receiver
      operating characteristic (FROC) of 20 radiologists detecting subsegmental-sized
      pulmonary emboli in a porcine model using either contrast-enhanced computed
      tomography (CT) or digital subtraction (DS) pulmonary angiography. Colored
      methacrylate beads (4.2 and 3.8 mm diameter) were injected into 9 anesthetized
      juvenile pigs. CT and DS pulmonary angiography images were obtained before and
      after a pulmonary infiltrate was introduced into the lower lobes. Following
      imaging, the pigs were euthanized, and the pulmonary arterial tree was cast using
      clear methacrylate allowing direct visualization of emboli. The 20 radiologists
      used a custom-made computer application to display the images on their personal
      computer and record their diagnoses. The results were mailed electronically to
      the coordinating center for comparison with the cast of the pulmonary
      vasculature. Twenty-three emboli were included in the statistical analysis.
      Overall sensitivity for spiral CT and angiography, respectively, was: 60 +/- 18%
      and 72 +/- 11% (P = 0.06). Positive predictive value for spiral CT and
      angiography, respectively, was: 49 +/- 24% and 58 +/- 23% (P = 0.25). There was a
      large variation in both sensitivity and positive predicted values between
      Readers. There was no difference in sensitivity or positive predictive value
      between radiologists from community or academic centers (P > 0.27). FROC analysis
      showed no significant difference between CT or DS (P = 0.27). In conclusion, in
      this porcine model, there is no overall diagnostic advantage to using DS
      pulmonary angiography rather than contrast-enhanced spiral CT for the diagnosis
      of PE when images are interpreted by radiologists located in either academic or
      community hospital settings.

PMID- 15729120
TI  - Imaging of left ventricular assist devices.
AB  - Left ventricular assist devices are used as a bridge to recovery, a bridge to
      transplant, or a permanent alternative to cardiac transplant. This exhibit
      demonstrates the imaging appearance of commonly used left ventricular assist
      devices and their complications.

PMID- 15729121
TI  - Imaging appearance of thoracic amyloidosis.
AB  - Amyloidosis is a disease caused by the deposition of abnormal proteins within
      extracellular soft tissues, and affects the respiratory tract in 50% of cases.
      Pulmonary involvement may be secondary to systemic disease or due to the
      accumulation of locally produced amyloid, and this differentiation has important
      prognostic and therapeutic implications. This pictorial essay, using cases of
      biopsy-proven respiratory tract amyloidosis, aims to depict the spectrum of
      imaging findings, and those of CT in particular, that can be of use in
      distinguishing between the 2 typical patterns of the disease.

PMID- 15729122
TI  - Multiple rheumatoid nodules with rapid thin-walled cavity formation producing
      pneumothorax.
AB  - We report a rare case of multiple rheumatoid nodules that on chest CT
      demonstrated peripheral location with thin-walled cavity formation, rapid
      increase in size within several months, and complicating pneumothorax,
      pneumomediastinum, and subcutaneous emphysema due to bronchopleural fistula
      formation.

PMID- 15729123
TI  - Pericardial rupture after blunt chest trauma.
AB  - Traumatic pericardial rupture is a rare injury with potentially fatal
      consequences, usually occurring in patients who have sustained other severe
      injuries of the chest and abdomen. Diagnosis is difficult and is commonly made at
      the time of surgery. Radiographs and computed tomography of the chest may provide
      clues to the diagnosis. We present one case of left pleuropericardial rupture and
      another of traumatic diaphragmatic pericardial rupture.

PMID- 15729124
TI  - Radiologic findings in primary pulmonary plasmacytoma.
AB  - Plasmacytoma is an uncommon tumor and is rarely encountered as a primary
      pulmonary neoplasm. Herein we describe the conventional radiographic and computed
      tomographic findings in a patient with a primary pulmonary plasmacytoma.

PMID- 15729125
TI  - Behcet disease complicated by diffuse alveolar damage.
AB  - We report an extremely rare case of Behcet disease complicated by diffuse
      alveolar damage, which was fatal in this patient. It manifested as progressive
      diffuse ground-glass attenuation in both lungs on chest radiographs and high
      resolution CT. Ground-glass attenuation was confirmed histopathologically as
      diffuse alveolar damage without identified etiology by open lung biopsy.

PMID- 15729126
TI  - Metastatic meningioma to the lungs.
AB  - Meningioma with extracranial metastases is a rare occurrence. However, the lungs
      are the most common site of extracranial metastases. We describe a case of a
      patient with recurrent intracranial meningioma and intrapulmonary metastases.

PMID- 15729127
TI  - Pulmonary capillary hemangiomatosis: multidetector row CT findings and clinico
      pathologic correlation.
AB  - Pulmonary capillary hemangiomatosis (PCH) is a rare potentially fatal cause of
      post-capillary pulmonary hypertension. We present a case demonstrating the CT
      imaging features of the underlying capillary proliferation and invasion of
      alveoli and vasculature.

PMID- 15729128
TI  - Functional somatotopy in sensorimotor cortex.
AB  - In an effort to understand the highly distributed somatotopy of primary motor
      cortex, this review draws on principles derived from studies of auditory, visual
      and somatosensory cortical areas. In each case, a behaviorally important feature
      or function is overlaid in multiple locations on an underlying topographic map of
      the peripheral sensory surface. Recent studies of hand muscle synergies suggest
      the types of two-dimensional functional axes that might reasonably be mapped to
      the two-dimensional surface of the primary motor cortex. However, other research
      emphasizes that even a functional somatotopy must be extremely flexible.

PMID- 15729129
TI  - Fractional anisotropy-based divisions of midsagittal corpus callosum.
AB  - The authors first divided the midsagittal corpus callosum of 22 healthy
      volunteers using three different subdivision methods: Witelson's geometric
      subdivision, boundary model-based subdivision, and medial model-based
      subdivision. Next, subdivisions of the corpus callosum were clustered on the
      basis of homogeneity of the fractional anisotropy values as produced from
      diffusion tensor images. Nine subregions of corpus callosum, similar in location
      and size, were successfully clustered when medial model-based or boundary model
      based subdivisions were applied. These nine subregions of the corpus callosum
      were different from the seven subregions defined by Witelson's geometric
      subdivision, especially at the anterior and posterior tips of the corpus
      callosum. Our method of corpus callosum division can be potentially utilized to
      assess structural changes in the midsagittal corpus callosum.

PMID- 15729130
TI  - Role of matrix metalloproteinase-9 in a mouse model for amyotrophic lateral
      sclerosis.
AB  - The pathogenesis of amyotrophic lateral sclerosis remains poorly understood, but
      microglial and astroglial activation are thought to contribute to motor neuron
      death. Evidence suggests that matrix metalloproteinase-9 (MMP-9) is a mediator of
      this deleterious effect. In this study, we evaluated the effect of MMP-9 on the
      pathogenesis of amyotrophic lateral sclerosis. Although marked microglial and
      astroglial proliferation was seen in the spinal cord and in-vitro studies proved
      MMP-9 to be produced by these cells, deletion of the MMP-9 gene in SOD1(G93A)
      mice accelerated rather than delayed the motor neuron disease and significantly
      reduced survival. Our results suggest that the effect of MMP-9 on mutant
      superoxide dismutase-1 (SOD1)-induced motor neuron disease is protective rather
      than hazardous. Therefore, the effect of pharmacological inhibition of MMP-9
      activity is unlikely to be of therapeutical benefit in amyotrophic lateral
      sclerosis.

PMID- 15729131
TI  - Candesartan reduces superoxide production after global cerebral ischemia.
AB  - Excessive superoxide production after cerebral ischemia is known to mediate
      neuronal injury. Angiotensin II type 1 receptor activation results in production
      of superoxide, but whether angiotensin II type 1 receptor blockade prevents
      production of superoxide and subsequent neuronal injury after ischemia remains
      unclear. Normotensive rats received the angiotensin II type 1 receptor blocker,
      candesartan or only vehicle before induction of global cerebral ischemia.
      Approximately 30% of the hippocampal CA1 neurons survived in candesartan-treated
      animals, whereas only 2% of neurons survived in vehicle-treated animals.
      Superoxide production was significantly less in these vulnerable neurons in
      candesartan-treated animals than in vehicle-treated animals. Angiotensin II type
      1 receptor may have an essential role in superoxide production and subsequent
      injury in vulnerable neurons after global cerebral ischemia.

PMID- 15729132
TI  - Magnetoencephalography identifies rapid temporal processing deficit in autism and
      language impairment.
AB  - Deficient rapid temporal processing may contribute to impaired language
      development by interfering with the processing of brief acoustic transitions
      crucial for speech perception. Using magnetoencephalography, evoked neural
      activity (M50, M100) to two 40 ms tones passively presented in rapid succession
      was recorded in 10 neurologically normal adults and 40 8-17-year-olds with
      autism, specific language impairment, Asperger syndrome or typical development.
      While 80% of study participants with intact language (Asperger syndrome, typical
      development, adults) showed identifiable responses to the second tone, which
      presented rapid temporal processing demands, 65% of study participants with
      impaired language (autism, specific language impairment) did not, despite having
      shown identifiable responses to the first tone. Rapid temporal processing
      impairments may be fundamentally associated with impairments in language rather
      than autism spectrum disorder.

PMID- 15729133
TI  - CA2: the most vulnerable sector to bicuculline exposure in rat hippocampal slice
      cultures.
AB  - The vulnerability of the CA2 sector to chronic exposure to bicuculline was
      investigated in rat hippocampal slice cultures. Selective neuronal cell death was
      observed only in the CA2 sector after exposure to 6 microM bicuculline for 12 h,
      but the effect of the cell toxicity extended to the CA3 sector after 24 h. The
      effect was increased by adding 20 microM roscovitine but was reduced by adding
      200 nM omega-agatoxin IVA. Bicuculline also induced a calcium influx into
      neuronal cells mainly in the CA2 sector. These results suggest that CA2 is the
      most vulnerable sector to bicuculline exposure in hippocampal slice cultures, and
      that neuronal cell death in the CA2 sector involves the P/Q-type voltage
      dependent calcium channel.

PMID- 15729134
TI  - Could activity in anterior frontal regions predict performance on declarative
      memory tests?
AB  - Few studies have tested the correlation between traditional declarative memory
      scores and functional brain imaging measures of memory. We examined the
      predictable capabilities of magnetoencephalography-derived measures, scanned
      during a high-load encoding-memory task, in the immediate (LM-1) and delayed (LM
      2) recall from the Wechsler memory scale. The number of activity sources on the
      left frontal pole (between 300 and 600 ms) predicted scores in LM-1 and LM-2.
      Collapsing the activity in the left frontal pole and the orbitofrontal cortex
      increased the goodness of the solution for the LM-2 scores. The fact that rostral
      frontal measures achieved significant values highlights the importance of
      executive processes, such as the implementation of memory strategies and top-down
      control mechanisms, in the performance of high-load memory tasks.

PMID- 15729135
TI  - Controlling arterial blood pressure using a computer-brain interface.
AB  - There has been recent interest in the concept of connecting a computer to the
      brain to control brain functions. However, there are challenges that must be
      overcome in developing such a computer-brain interface, including a selection of
      nucleus that is stimulated, and an implantable electrode and electrical
      stimulator. Another important issue is the designing of the controller, that is,
      determining how to encode as an electrical signal the information to be sent to
      the brain. We have applied system identification theory, a method for evaluating
      dynamic characteristics of a system, to the arterial blood pressure control
      system of the brain. Our results show that (1) the stimulation-arterial blood
      pressure response relationship can be described as a mathematical model, which
      gives a good prediction of the arterial blood pressure response, facilitating the
      designing of a computer-brain interface, and (2) the arterial blood pressure can
      be actually controlled using a computer-brain interface.

PMID- 15729136
TI  - Rapid categorization of natural scenes in monkeys: target predictability and
      processing speed.
AB  - Three monkeys performed a categorization task and a recognition task with briefly
      flashed natural images, using in alternation either a large variety of familiar
      target images (animal or food) or a single (totally predictable) target. The
      processing time was 20 ms shorter in the recognition task in which false alarms
      showed that monkeys relied on low-level cues (color, form, orientation, etc.).
      The 20-ms additional delay necessary in monkeys to perform the categorization
      task is compared with the 40-ms delay previously found for humans performing
      similar tasks. With such short additional processing time, it is argued that
      neither monkeys nor humans have time to develop a fully integrated object
      representation in the categorization task and must rely on coarse intermediate
      representations.

PMID- 15729137
TI  - Functional disconnection of the semantic networks in schizophrenia.
AB  - Patients with schizophrenia exhibit deficits in semantic processing, which can
      form the basis of thought disorders. The objective of this study was to explore
      functional connectivity between the activated areas during semantic processing in
      schizophrenia. Twelve patients with schizophrenia and 12 healthy controls were
      studied with [15O]H2O positron-emission tomography during semantic judgment. The
      expected activation in the left inferior occipitotemporal cortex significantly
      correlated with several other regional activations in normal study participants,
      but with no other regional activations in patients with schizophrenia. This
      finding suggests that schizophrenia involves a disconnection of semantic
      networks. The resultant distortion in semantic processing may have an impact on
      thought disorders.

PMID- 15729138
TI  - RT-PCR analysis of Tecta, Coch, Eya4 and Strc in mouse cochlear explants.
AB  - Tecta, Coch, Eya4 and Strc are mouse orthologs of four human deafness-associated
      genes. Their expression is markedly restricted to specific cell types in
      cochleae. Cochleae were dissected on embryonic day 15 and cultured in vitro.
      Relative messenger RNA abundance of each gene was quantified by RT-PCR and
      compared in-vivo cochleae of equivalent embryonic age. After 48 h in culture, in
      vivo and explant Strc expression levels were equivalent, Eya4 level reduced in
      explanted tissues, and expression of Tecta and Coch did not show the expected
      temporal rise. Expression of these genes was detectable even after 96 h. These
      results suggest that it is feasible to test the expression of inner ear specific
      genes in explanted cochleae.

PMID- 15729139
TI  - Viewing touch improves tactile sensory threshold.
AB  - Previous research on multisensory integration has demonstrated that viewing the
      stimulated body part enhances discrimination ability. Participants in this
      experiment watched a video showing a hand being touched by a stick and a second
      video showing the stick touching the space beneath the hand. Sensory thresholds
      of the index fingers were tested with von Frey filaments. We found significant
      enhancements of the sensory threshold after showing the video with the touched
      hand but not after showing the video with no touch of the hand. This enhancement
      was specific for the index finger shown in the video. The results link the
      visuotactile enhancement of this study to the observation of touch rather than to
      the simple depiction of the body part.

PMID- 15729140
TI  - Luminance adaptation increased the contrast sensitivity of retinal ganglion
      cells.
AB  - In the present study, the activity changes of chicken retinal ganglion cells in
      response to light stimuli with defined contrast were investigated, in the
      presence of various levels of sustained background illumination. Following a step
      increase of light illumination, the firing rate of most retinal ganglion cells
      increased abruptly, and then decreased to a steady-state level with a much lower
      firing rate during the sustained application of light. However, when a test flash
      was applied, which superimposed the prolonged background illumination, an
      increased firing rate was observed. Moreover, the neuron firing rate was
      increased to a greater extent when the intensity of the background illumination
      was higher. This may suggest that the neuron sensitivity can be modified by the
      background illumination level, although the neuron firing rate was reduced during
      sustained illumination.

PMID- 15729142
TI  - An electron microscopy study of changes in dense core vesicles of PC12 cells
      following pulse depolarization.
AB  - Depolarization of PC12 cells by brief pulses of high K+ or ATP produces
      electrophysiological responses consistent with the quantal release of ATP.
      Quantitative electron microscopy was used to validate whether the same protocol
      changed dense core vesicles containing endogenous ATP. The total vesicle number
      fell by 54% after high K+ and by 21% after ATP. Perimembrane vesicles were
      significantly depleted by high K+, yet unchanged by ATP, suggesting differential
      contribution by vesicle pools to distinct stimuli during the release process.
      Vesicle changes were consistent with vesicular release mechanisms for the
      liberation of discrete packets of endogenous ATP. These data thus support the use
      of clustered PC12 cells as a model to study the process of ATP release.

PMID- 15729141
TI  - Ethanol induces GAD67 and VGAT in slice cultures of newborn rat cerebral cortex.
AB  - Exposure of the developing brain to ethanol disposes to the fetal alcohol
      syndrome, causing changes in the neurotransmitter systems of glutamate and gamma
      amino butyric acid (GABA). However, expression of genes involved in GABA
      synthesis, vesicular and transmembrane transport has not been investigated so
      far. We exposed organotypic slice cultures of newborn rat cerebral cortex to
      ethanol (100 mM) for 4 days and observed a significant induction of the enzyme
      producing GABA (GAD67, +21%) and the vesicular transporter VGAT (+112%), whereas
      the expression of the transmembrane transporters did not differ from control
      conditions. In summary, ethanol exposure of the developing cortex induces
      GABAergic genes, which might facilitate the excitatory functions of GABA during
      development.

PMID- 15729143
TI  - Suppression of morphine withdrawal syndrome by interleukin-2 and its gene.
AB  - The naloxone-precipitated withdrawal syndrome in mice and rats after intrathecal
      injection of recombinant human interleukin-2 protein (rIL-2) or its gene was
      studied. The results showed that rIL-2 could significantly decrease the number of
      jumps in mice. In rats, rIL-2 significantly suppressed irritating, diarrhea,
      weight loss, abnormal posture and salivation. Tendencies towards reductions in
      teeth chewing and dog-shaking were also observed. Furthermore, pcDNA3-IL-2 (8
      microg DNA) had a similar effect as 1x10 IU rIL-2 protein on inhibition of
      morphine withdrawal syndrome in mice, and the expression of rIL-2 protein in
      spinal cord could be detected for 6 days. These findings provided further
      evidence for the neuroregulatory function of an immunological molecule such as IL
      2.

PMID- 15729144
TI  - Proteolysis of NR2B by calpain in the hippocampus of epileptic rats.
AB  - Overactivation of N-methyl-D-aspartate receptors is known to mediate
      excitotoxicity due to excessive entry of calcium, leading to the activation of
      several calcium-dependent enzymes. Calpains are calcium-activated proteases that
      appear to play a role in excitotoxic neuronal death. Several cellular proteins
      are substrates for these proteases, particularly the N-methyl-D-aspartate
      receptor. Recently, cleavage of NR2B subunits has been implicated in excitotoxic
      neurodegeneration in ischemia. In this work, we investigated the proteolysis by
      calpains of NR2B subunits of the N-methyl-D-aspartate receptor in the hippocampus
      of epileptic rats. Our results show that cleaved forms of NR2B subunits are
      formed after status epilepticus, in the same areas of the hippocampus where
      calpain activation was detected by immunohistochemical staining of calpain
      specific spectrin breakdown products.

PMID- 15729145
TI  - Basal ganglia and language: phonology modulates dopaminergic release.
AB  - Basal ganglia have been implicated in syntactic and phonological processes, but
      direct evidence has been scarce. Here, we used [11C]raclopride and positron
      emission tomography to measure modulations of the dopaminergic system induced by
      phonological or syntactic processing. Two significant effects were found. First,
      the level of accuracy in phonological processing significantly correlated with
      tracer binding potential in the left caudate nucleus. Second, the speed in
      phonological processing significantly correlated with tracer binding potential in
      the left putamen. Thus, a more accurate and fast phonological processing was
      associated with a reduced dopamine requirement in the left striatum. These
      findings show that the striatal dopaminergic system plays an essential role in
      grammatical processes that form the core of human language.

PMID- 15729146
TI  - No association of EGF polymorphism with schizophrenia in a Japanese population.
AB  - Epidermal growth factor (EGF) signal regulates the development of dopaminergic
      neurons and monoamine metabolism. It is suggested that EGF protein levels are
      decreased in the brain and blood of patients with schizophrenia. A recent study
      has reported that a polymorphism in EGF gene (rs4444903) is associated with
      schizophrenia in Finnish men. To confirm this association for another population
      in larger samples, we conducted a case-control association study on a Japanese
      population (337 cases and 421 controls). No significant difference was observed
      in both the allelic and genotype distribution between cases and controls in
      women, men and total samples. Our results suggest that the polymorphism in EGF
      gene might not confer increased susceptibility for schizophrenia in a Japanese
      population.

PMID- 15729147
TI  - Effects of value and reward magnitude on feedback negativity and P300.
AB  - Feedback negativity is a negative component of the event-related brain potential
      observed 250-300 ms after feedback stimuli. The present study investigated the
      effects of value (correct or incorrect) and reward magnitude (no, small or large)
      on feedback negativity and P300. Feedback negativity was larger after incorrect
      feedback than after correct feedback, irrespective of reward magnitude. In
      contrast, P300 amplitude increased with reward magnitude, irrespective of value.
      The amplitude of feedback negativity was correlated with a trait score of
      negative affect and not positive affect, whereas P300 amplitude was correlated
      with positive affect and not negative affect. These results suggest that value
      and reward magnitude are processed separately in the brain.

PMID- 15729148
TI  - Effects of nitric oxide synthase isoform deletion on oxytocin and vasopressin
      messenger RNA in mouse hypothalamus.
AB  - The effects of neuronal, endothelial, or inducible nitric oxide synthase gene
      disruption on the expression of oxytocin and vasopressin gene were examined in
      the hypothalamus (paraventricular, supraoptic, suprachiasmatic, and anterior
      commissural nuclei) and extrahypothalamus (bed nucleus of the stria terminalis).
      The oxytocin messenger RNA levels in the anterior commissural nucleus of neuronal
      nitric oxide synthase knockout mice were significantly higher than in control
      mice, but not in endothelial or inducible nitric oxide synthase knockout mice. In
      contrast, no significant effects of neuronal, endothelial, or inducible nitric
      oxide synthase gene disruption on oxytocin and vasopressin messenger RNA levels
      in the other hypothalamic and extrahypothalamic nuclei were observed. These
      results suggest that neuronal nitric-oxide-synthase-derived nitric oxide may be
      involved in the regulation of oxytocin gene expression in the anterior
      commissural nucleus.

PMID- 15729150
TI  - Misclassification of the stages of syphilis: implications for surveillance.
AB  - SHORT SUMMARY: Syphilis cases were reviewed to see if reported stages met the
      Centers for Disease Control and Prevention case definition. Classification was
      excellent for primary and secondary and good for late latent, but half of early
      latent and unknown duration were misclassified. New surveillance definitions are
      suggested, comments requested. BACKGROUND: Uncertainty when staging latent
      syphilis should lead clinicians to call it late latent (requires more treatment)
      and disease investigators to call it early latent (priority for partner
      investigation). Accurate surveillance requires consistent case definitions.
      OBJECTIVE: Assess validity of reported syphilis stages. METHODS: Record reviews
      in 6 jurisdictions to determine if reported cases met the Centers for Disease
      Control and Prevention case definitions. RESULTS: Nine hundred seventy-three
      records from 6 jurisdictions in 2002 showed excellent agreement for reported
      primary (94.0%) and secondary (95.4%), good agreement for late latent (80.2%),
      and poor agreement for early latent (48.4%) and unknown duration (49.7%). Unknown
      duration (age < or =35 and nontreponemal test titer > or =32) was often
      misinterpreted to mean "not known." Early latent (within the past year,
      documented: seroconversion, fourfold titer increase, symptoms, or contact with an
      independently documented early syphilis case) was often misinterpreted to include
      patients with risky behavior, young age, or high nontreponemal test titers.
      CONCLUSIONS: The unknown duration stage should be dropped. Surveillance of latent
      syphilis would be more consistent if cases were reported as having high or low
      titers on nontreponemal test. Alternative approaches are solicited from readers.

PMID- 15729151
TI  - Sexually transmitted infections in rural Madagascar at an early stage of the HIV
      epidemic: a 6-month community-based follow-up study.
AB  - BACKGROUND AND OBJECTIVES: Sexually transmitted infections (STIs) in Madagascar
      have primarily been monitored in selected groups of patients attending STI
      clinics in major cities as part of the HIV surveillance program in Madagascar.
      GOAL OF THE STUDY: The aim of the study was to provide complementary data related
      to STI prevalence in a general rural population. STUDY DESIGN: STIs were
      investigated in 643 subjects aged 15 to 49 years as part of a cross-sectional
      morbidity study of urogenital schistosomiasis. Infection rates were reassessed 3
      weeks and 6 months after systematic STI treatment at baseline. RESULTS: Neisseria
      gonorrhoeae (Ng), Chlamydia trachomatis (Ct), Mycoplasma genitalium (Mg),
      Trichomonas vaginalis (Tv), and/or antibodies to Treponema pallidum (Tp) were
      diagnosed in 125 (37.5%) of 333 women and in 83 (26.8%) of 310 men. In addition,
      49% of the women and 28% of the men were infected with herpes simplex virus-2.
      Six (0.9%) subjects were found HIV-antibody positive. Between the 3-week and 6
      month follow-up surveys Ng, Ct, and/or Mg prevalence increased most prominently
      in women aged 15 to 24 years. CONCLUSION: Study findings suggest that rural areas
      in Madagascar should be as closely monitored and assisted in STI and HIV control
      as their urban counterparts. Following the current consensus, young adults should
      constitute a priority target group in the control programs.

PMID- 15729152
TI  - Is there an association between alcohol consumption and sexually transmitted
      diseases? A systematic review.
AB  - OBJECTIVE/GOAL: The objective of this study was to conduct a systematic review of
      published literature on the association between problematic alcohol consumption
      and sexually transmitted diseases (STDs). DESIGN: Using a MEDLINE search (1995
      2003) and article references, we identified articles that described measures of
      alcohol consumption and STDs and presented data on their association. For each
      eligible study, we classified the alcohol consumption measure as specific
      (problem drinking) or general, and examined study designs, study populations, STD
      measures, and results. RESULTS: Of 42 eligible studies, 11 included specific
      measures of problem drinking, of which 8 found a significant association between
      alcohol consumption and at least 1 STD. The relationship did not appear to vary
      according to gender or pattern of alcohol consumption assessed. CONCLUSIONS: The
      literature supports an overall association between problematic alcohol
      consumption and STDs, although their causal relationship cannot be determined
      with certainty from these observational studies. The findings have implications
      for prevention planners, clinicians, and individual patients at risk of STDs.

PMID- 15729153
TI  - Prevalence of Chlamydia trachomatis in asymptomatic Brazilian military
      conscripts.
AB  - BACKGROUND: Few data are available on the prevalence and risk factors for
      Chlamydia trachomatis infection among young men in Brazil. OBJECTIVES: To assess
      prevalence and risk factors for C. trachomatis infection in male military
      conscripts. METHODS: In 2000, 627 young men recruited for military service in
      Goiania, Goias, Brazil, were enrolled in this cross-sectional study. Participants
      completed a demographic and sexual risk behavior questionnaire, and urine samples
      were screened for C. trachomatis by polymerase chain reaction. RESULTS: The
      prevalence of chlamydial infection among asymptomatic conscripts was 5.0% (95%
      confidence interval [CI], 3.3-7.3). In multivariate analysis, failure to use
      condoms (odds ratio [OR](adjusted) 5.3; 95% confidence interval [CI], 1.2-23.4; P
      = 0.028) and having more than 2 sexual partners in the last 2 months
      (OR(adjusted) 2.6; 95% CI, 1.1-6.9; P = 0.049) were significantly associated with
      positivity for C. trachomatis. CONCLUSIONS: A substantial number of asymptomatic
      young male military recruits were infected with C. trachomatis, and risk factors
      for this infection were related to sexual behavior. Further research is required
      to determine if routine screening may be considered as a strategy to reduce
      prevalence among this population.

PMID- 15729154
TI  - Incidence of sexually transmitted diseases and HIV infection related to perceived
      HIV/AIDS threat since highly active antiretroviral therapy availability in men
      who have sex with men.
AB  - OBJECTIVE: Concerns have been expressed regarding increase in risky sex because
      of the availability of antiretroviral treatments in Western countries. GOAL: The
      goal of this longitudinal study was to investigate the association between highly
      active antiretroviral therapy (HAART)- and postexposure prophylaxis-related
      beliefs and the incidence of sexually transmitted diseases (STDs) and new HIV
      infections in men who have sex with men (MSM). STUDY: Data on the incidence of
      STDs and new HIV infection, and the level of agreement with different HAART- and
      PEP-related beliefs from 151 HIV-negative MSM were compiled. RESULTS: Of all MSM,
      65.6% tested negative for any STDs and 7 men HIV seroconverted. Perceiving less
      HIV/AIDS threat since HAART availability and younger age were significantly
      associated with a higher incidence of STDs. Perceiving less need for safe sex
      since HAART availability was significantly associated with an increased
      likelihood of HIV seroconversion. CONCLUSIONS: The results support the assumption
      that there is an association between the incidence of STDs and a decreased
      perception of HIV/AIDS threat resulting from HAART availability. Less perceived
      need for safe sex since HAART availability was associated with HIV
      seroconversion.

PMID- 15729155
TI  - Resurgence of risk behaviors among men who have sex with men: the case for HAART
      realism.

PMID- 15729156
TI  - Antimicrobial resistance of Neisseria gonorrhoeae in selected World Health
      Organization Southeast Asia Region countries: an overview.
AB  - BACKGROUND AND OBJECTIVES: A Gonococcal Antimicrobial Susceptibility Program
      (GASP) under the World Health Organization South East Asia Region (WHO SEAR) is
      continuing in India and neighboring countries and is being coordinated by the WHO
      Regional Reference Laboratory (RRL), Vardhman Mahavir Medical College, and
      Safdarjung Hospital, New Delhi. GOAL: The present communication describes the
      current status and trends of antimicrobial resistance patterns of Neisseria
      gonorrhoeae, isolated in different focal-point laboratories under GASP, as
      presented in WHO SEAR intercountry consultative meeting conducted in December
      2001. STUDY: Seven laboratories from India and 1 each from Bangladesh, Sri Lanka,
      and Nepal presented their data for the year 2000/2001. In addition, RRL Delhi,
      Bangladesh, and Sri Lanka presented data for the years 1995 to 2001, 1997 to
      2001, and 1996 to 2000, respectively. Either National Committee for Clinical
      Laboratory Standards or calibrated dichotomous sensitivity technique was used in
      the different laboratories for determining antimicrobial susceptibility. RESULTS:
      It was observed that in the Indian laboratories, penicillin resistance varied
      from 20% to 79%, tetracycline resistance from 0% to 45.6%, and ciprofloxacin from
      10.6% to 100%. Chromosomal, as well as plasmid-mediated resistance, was observed.
      The strains were reported to be less sensitive to ceftriaxone in 5 out of 7
      laboratories, while none reported spectinomycin resistance. The reasons for wide
      variation in the results could be due to geographical strain difference in
      different parts of this vast country. At Sri Lanka, gonococci showed resistance
      towards penicillin (96.8%) and ciprofloxacin (8.2%). Bangladesh reported N.
      gonorrhoeae with ciprofloxacin (76%), penicillin (33%), and tetracycline (50%)
      resistance and decreased susceptibility to ceftriaxone (1.5%). Both the
      laboratories did not report any spectinomycin resistance. The resistance trends
      in these 2 centers and the RRL, New Delhi, showed different patterns. CONCLUSION:
      The report indicates the necessity for continuous surveillance of antimicrobial
      resistance pattern in this region of WHO for establishing antimicrobial policy
      guidelines for management of this common but important sexually transmitted
      infection (STI) pathogen, known to facilitate human immunodeficiency virus (HIV)
      infection. It also highlights the importance of ensuring quality assurance in the
      techniques in order to generate uniform data.

PMID- 15729157
TI  - Endometrial plasma cells: do they indicate subclinical pelvic inflammatory
      disease?
AB  - BACKGROUND: Subclinical pelvic inflammatory disease (PID) is a common condition
      among women with lower genital tract infection and is believed to be responsible
      for a greater proportion of PID-related sequelae than acute PID. Subclinical PID
      is diagnosed histologically after endometrial biopsy. In the literature, many
      different histologic criteria have been used to define subclinical PID. GOAL: To
      determine if endometrial plasma cells are commonly found in women at low
      likelihood of PID. STUDY: A cross-sectional study of 33 women undergoing tubal
      ligation and at low likelihood of PID was performed. At the time of tubal
      ligation, study participants underwent visualization of pelvic organs and an
      endometrial biopsy, which was analyzed for the presence of neutrophils and plasma
      cells. Demographic, clinical, and microbiologic data were compared among women
      with and without endometrial plasma cells. RESULTS: Endometrial plasma cells were
      identified in one third (33%) of the asymptomatic, fertile, healthy women in our
      cohort. The presence of plasma cells was not associated with lower genital tract
      infection, including bacterial vaginosis. Laparoscopic evidence of fallopian tube
      damage was similar in patients with and without endometrial plasma cells (22% in
      each group). CONCLUSION: Plasma cells are commonly found in the endometria of
      healthy women and may not represent upper genital tract inflammation.

PMID- 15729158
TI  - Randomized trial of supplementary interviewing techniques to enhance recall of
      sexual partners in contact interviews.
AB  - BACKGROUND: People with multiple sex partners tend to forget a significant
      proportion when recalling them. METHODS: Randomized trial of supplementary
      interviewing techniques during routine partner notification contact interviews
      for chlamydia, gonorrhea, and syphilis in Colorado Springs, CO. Cases with
      multiple sex partners in the last 3 months (n = 123) participated. Interviewers
      prompted nonspecifically and read back the list of elicited partners after cases
      recalled partners on their own. We then randomly assigned cases to receive 1 of 3
      sets of recall cues: (1) an experimental set of cues consisting of locations
      where people meet partners, role relationships, network ties, and first letters
      of names; (2) another experimental set including common first names; and (3)
      control cues referring to individual characteristics (e.g., physical appearance).
      RESULTS: Nonspecific prompting and reading back the list each increased the
      number of additional partners elicited and located by 3% to 5% on average. On
      average, the combined location/role/letter/network cues elicited more additional
      partners (0.57) than did the first-name (0.29) and individual characteristics
      (0.28) cues. The location and first-name cues were the most effective in
      eliciting located partners. The supplementary techniques increased the number of
      new cases found by 12% and, importantly, identified branches of the sexual
      network that would not otherwise have been discovered. CONCLUSION: Elicitation of
      sex partners can be enhanced in contact interviews with simple interviewing
      techniques, resulting in improved network ascertainment and sexually transmitted
      disease case finding.

PMID- 15729159
TI  - Time to treatment for women with chlamydial or gonococcal infections: a
      comparative evaluation of sexually transmitted disease clinics in 3 US cities.
AB  - BACKGROUND: Many women with positive screening tests for chlamydia or gonorrhea
      are not promptly treated and are at risk for complications and further disease
      transmission. Improved methods for notifying infected patients might increase
      timely treatment in this population. GOAL: Describe notification procedures at
      STD clinics in Washington, DC; Los Angeles; and San Diego and compare timeliness
      of treatment during 2000 to 2002. STUDY: Interviews were conducted to determine
      methods for notifying infected patients. Data were abstracted from 327 medical
      records of women with chlamydia or gonorrhea who had not been treated
      presumptively. The interval between specimen collection and treatment ("time to
      treatment") was calculated. RESULTS: Each clinic had different procedures for
      notifying untreated infected women. Among those treated, the median time to
      treatment was 18 days in Washington, DC, and 8 days in Los Angeles. In San Diego,
      the median time to treatment was initially 14 days, which improved to 7 days
      after patient-notification procedures were changed. CONCLUSION: Simple changes in
      patient notification procedures can decrease time to treatment at STD clinics.
      STD programs should evaluate time to treatment and institute methods for
      efficient patient follow-up.

PMID- 15729160
TI  - Evaluation of opa-based real-time PCR for detection of Neisseria gonorrhoeae.
AB  - OBJECTIVES: Detection of Neisseria gonorrhoeae by commercial and in-house-based
      assays has been hampered by false-positive and false-negative results. The
      current study describes a sensitive and specific real-time 5'-nuclease PCR assay
      targeting a 90-bp region of the multicopy opa gene. GOAL: To evaluate the
      sensitivity and specificity of this assay in detection of gonococcus. STUDY:
      Sensitivity and specificity were determined by testing a panel of 173
      microorganisms. In addition, 135 clinical samples previously evaluated by 4
      nucleic acid amplification methods were also tested. RESULTS: A sensitivity of 1
      copy per reaction was achieved. Positive results were only obtained for N
      gonorrhoeae strains including 20 cppB-negative strains. Overall, 134 of 135
      clinical sample results agreed with the consensus nucleic amplification methods.
      CONCLUSION: This study demonstrates opa-based target can be used as an accurate
      and rapid PCR assay for the detection of N gonorrhoeae in clinical specimens.

PMID- 15729161
TI  - Similar sexual behaviors with casual partners among gay men with and without a
      regular partner.
AB  - OBJECTIVES: We hypothesized that men in a relationship would engage in less risky
      sexual activity with their casual partners compared to men with only casual
      partners. STUDY: Cross-sectional data were collected between 1999 and 2003 in a
      study of young human immunodeficiency virus-seronegative gay men in Vancouver,
      British Columbia. We assessed the substance use and sexual behaviors of 156 men
      and compared those having casual partners in addition to 1 regular partner for
      the duration of the previous year (n = 43) to those reporting only casual
      partners during the previous year (n = 113). RESULTS: Men with just 1 regular
      partner were not significantly different from men without a regular partner with
      regard to sexual behaviors reportedly engaged in with casual partners, self
      reported sexually transmitted infections diagnosed within the previous year, or
      demographic characteristics. Only previous use of poppers and higher frequencies
      of marijuana use were found among men without a regular partner. CONCLUSIONS: In
      our cohort, young gay men in a relationship do not appear less likely to engage
      in risky sex with casual partners than men with casual partners only.

PMID- 15729162
TI  - Clinical and immunologic aspects of cytomegalovirus infection in solid organ
      transplant recipients.
AB  - Primary cytomegalovirus (CMV) infection is a major cause of morbidity and
      mortality in recipients after solid organ transplantation (SOT). Widespread and
      prolonged use of antiviral drugs has changed the natural course of CMV disease by
      delaying its onset and causing drug resistance. CMV induces a strong cellular
      immune response, even in immunosuppressed patients, and has developed strategies
      to evade this immune surveillance. This review summarizes challenges in managing
      CMV infection in transplant recipients and highlights current insights in the
      cellular immune response against CMV.

PMID- 15729163
TI  - Up-regulation of interleukin-8, interleukin-10, monocyte chemotactic protein-1,
      and monocyte chemotactic protein-3 in peripheral blood monocytes in stable lung
      transplant recipients: are immunosuppression regimens working?
AB  - BACKGROUND: Alveolar macrophages are a major source of inflammatory cytokines and
      chemokines involved in the pathogenesis of lung transplant rejection and are
      derived from blood monocytes that migrate to the lung. Levels of monocyte
      cytokines and chemokines that may be relevant in transplant rejection have not
      previously been determined in transplant recipients. We hypothesized that
      production of these inflammatory mediators by blood monocytes may be up-regulated
      despite the use of potent immunosuppression therapy. METHOD: To investigate this,
      whole blood from 9 stable lung transplant recipients and 12 control volunteers
      was stimulated with lipopolysaccharide in vitro, and intracellular chemokine and
      cytokine production were determined with multiparameter flow cytometry. RESULTS:
      Monocyte production of chemokines interleukin (IL)-8, monocyte chemotactic
      protein (MCP)-1, and MCP-3, and anti-inflammatory cytokine IL-10 were
      significantly increased in the lung transplant group, but IL-6, tumor necrosis
      factor-alpha, IL-1alpha, IL-12, macrophage inflammatory protein-1alpha,
      macrophage inflammatory protein-1beta, and transforming growth factor-beta levels
      were unchanged. CONCLUSIONS: Because MCP-3 is a major chemoattractant for
      leukocytes to sites of antigenic challenge and is a natural ligand for MCP-1
      receptor, this novel finding has important implications for the pathogenesis of
      lung transplant rejection. We now provide evidence that current immunosuppression
      protocols have a limited effect on monocyte inflammatory cytokine production and
      do not adequately suppress monocyte IL-8, MCP-1, and MCP-3 chemokine production.
      Drugs that modulate the action of these chemokines may improve current protocols
      for reducing graft rejection. Intracellular chemokine and cytokine analysis with
      flow cytometry may be a more accurate indicator of immunosuppression than drug
      levels in these patients.

PMID- 15729164
TI  - A new animal model to assess angiogenesis and endocrine function of parathyroid
      heterografts in vivo.
AB  - BACKGROUND: It is still a matter of investigation how angiogenesis and
      restoration of gland perfusion determine graft function after free parathyroid
      autotransplantation. We provide a new animal model allowing simultaneous and
      repetitive in vivo assessment of angiogenesis and endocrine function of
      parathyroid transplants. METHODS: Fresh human parathyroid tissue from patients
      with secondary hyperparathyroidism was grafted into dorsal skinfold chamber
      preparations of athymic nude mice (CD1-nu; n=8). Equivalent pieces of the same
      human donor specimens were heat-inactivated and served as control grafts (n=7).
      RESULTS: In all animals receiving parathyroid transplants, intact human
      parathyroid hormone levels were detectable by species-specific enzyme-linked
      immunosorbent assay analysis of plasma samples on day 5 after transplantation and
      increased by 2.5-fold over the observation period (19 days) in contrast with
      controls. Plasma Ca levels revealed no differences between the groups. On day 5
      after transplantation, intravital fluorescence microscopy revealed murine
      angiogenic microvessels sprouting along nonperfused human donor vessels, and 1
      week later functional microvasculature was established in all parathyroid
      transplants. Histologic analysis revealed well-vascularized endocrine tissue. In
      contrast, control grafts were necrotic and partly resorbed; they exhibited no
      angiogenic activity or well-vascularized fat cells indicating fatty degeneration.
      In addition, species-specific Western blot analysis revealed vascular endothelial
      growth factor expression of parathyroid transplants rather than functional vessel
      density as the functional parameter of angiogenesis determining transplant
      function in vivo. CONCLUSION: This model may serve to understand mechanisms
      associated with specific parathyroid transplant angiogenesis and its significance
      for transplant function to optimize clinical success of autotransplantation in
      therapy-resistant patients.

PMID- 15729165
TI  - Methoxyethyl-modified intercellular adhesion molecule-1 antisense
      phosphorothiateoligonucleotides inhibit allograft rejection, ischemic-reperfusion
      injury, and cyclosporine-induced nephrotoxicity.
AB  - BACKGROUND: The addition of phosphorothioate (PS) groups to natural
      phosphodiester (PD) antisense oligodeoxynucleotides (oligo) prevents their in
      vivo hydrolysis by nucleases allowing an RNase-dependent elimination of targeted
      mRNA. To further improve oligo function 2'-methoxyethyl (ME) groups were attached
      to selected nucleotides at the 3'-end because ME groups block RNase activity.
      METHODS/RESULTS: ME modification of PS- or PD/PS-oligo targeting human
      intracellular adhesion molecule (ICAM)-1 mRNA significantly increased the degree
      and duration of the in vitro inhibitory effects without compromising selectivity
      and specificity. A 7-day intravenous or oral therapy with rat ME/PS-modified ICAM
      1 antisense oligo extended the survivals of kidney allografts. In addition, ME/PS
      modified ICAM-1 antisense oligo reduced ischemic-reperfusion injury in kidneys,
      as measured by glomerular filtration rate, creatinine levels, and infiltration
      with leukocytes. Finally, a 14-day treatment with cyclosporine (CsA)-induced
      nephrotoxicity in syngeneic kidney transplants correlated with both increased
      ICAM-1 protein expression and infiltration with leukocytes. Graft perfusion and
      treatment of recipients with ICAM-1 antisense ME/PS-oligo alleviated the
      nephrotoxic effect and decreased ICAM-1 expression and leukocyte infiltration.
      CONCLUSIONS: ME/PS-modified ICAM-1 antisense oligo is very effective in
      inhibiting the ICAM-1-dependent mechanism of graft infiltration and tissue damage
      involved in allograft rejection, ischemic-reperfusion injury, and CsA-induced
      nephrotoxicity.

PMID- 15729166
TI  - Inhibition of cellular immune responses to encapsulated porcine islet xenografts
      by simultaneous blockade of two different costimulatory pathways.
AB  - BACKGROUND: Transplantation of human islets has been successful clinically. Since
      human islets are scarce, we are studying microencapsulated porcine islet
      xenografts in nonobese diabetic (NOD) mice. We have evaluated the cellular immune
      response in NOD mice with and without dual costimulatory blockade. METHODS:
      Alginate-poly-L-lysine-encapsulated adult porcine islets were transplanted i.p.
      in untreated diabetic NODs and NODs treated with CTLA4-Ig to block CD28/B7 and
      with anti-CD154 mAb to inhibit CD40/CD40-ligand interactions. Groups of mice were
      sacrificed on subsequent days; microcapsules were evaluated by histology;
      peritoneal cells were analyzed by FACS; and peritoneal cytokines were quantified
      by ELISA. Controls included immunoincompetent NOD-Scids and diabetic NODs given
      sham surgery or empty microcapsules. RESULTS: Within 20 days, encapsulated
      porcine islets induced accumulation of large numbers of macrophages, eosinophils,
      and significant numbers of CD4 and CD8 T cells at the graft site, and all grafts
      were rejected. During rejection, IFNgamma, IL-12 and IL-5 were significantly
      elevated over sham-operated controls, whereas IL-2, TNFalpha, IL-4, IL-6, IL-10,
      IL-1beta and TGFbeta were unchanged. Treatment with CTLA4-Ig and anti-CD154
      prevented graft destruction in all animals during the 26 days of the experiment,
      dramatically inhibited recruitment of host inflammatory cells, and inhibited
      peritoneal IFNgamma and IL-5 concentrations while delaying IL-12 production.
      CONCLUSIONS: When two different pathways of T cell costimulation were blocked, T
      cell-dependent inflammatory responses were inhibited, and survival of
      encapsulated islet xenografts was significantly prolonged. These findings suggest
      synergy between encapsulation of donor islets and simultaneous blockade of two
      host costimulatory pathways in prolonging xenoislet transplant survival.

PMID- 15729167
TI  - Effect of pirfenidone on apoptosis-regulatory genes in chronic cyclosporine
      nephrotoxicity.
AB  - BACKGROUND: : Apoptosis was shown to play a role in the progression of fibrosis
      in a chronic cyclosporine A (CsA) nephrotoxicity animal model. In addition, the
      antifibrotic molecule pirfenidone (PFD) was shown to ameliorate fibrosis in this
      model. We evaluated the role of PFD on the expression of apoptosis-regulatory
      genes in the kidneys of CsA-treated rats. METHODS: : Rats were administered CsA
      7.5 mg/kg per day, CsA+PFD (250 mg/kg/day), vehicle (VH), or VH+PFD, and
      sacrificed at 28 days. Physiologic and histologic changes were studied, and
      apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP nick
      end labeling stain. The mRNA expression of pro-apoptotic genes p53 and Fas-ligand
      was evaluated by quantitative polymerase chain reaction, and that of Bcl-xL, an
      anti-apoptotic gene, was evaluated by Northern blot analysis. In addition to mRNA
      expression, immunohistochemical studies of caspase 3 were performed. RESULT: :
      PFD administration to CsA-treated rats significantly ameliorated nephrotoxicity.
      Apoptosis-positive cells were increased by CsA but significantly reduced by PFD
      treatment (68+/-19 vs. 3+/-1, P<0.01). In addition, PFD down-regulated the mRNA
      expression of CsA-induced p53 and Fas-ligand (P<0.01) and increased that of Bcl
      xL, previously reduced by CsA (P<0.01). Finally, PFD significantly down-regulated
      caspase 3 expression, present mostly on renal tubular epithelial cells. None of
      these changes were observed in VH-treated rats. CONCLUSION: : Whereas CsA favored
      the expression of pro-apoptotic genes, that effect was ameliorated by PFD.
      Because apoptosis can partly explain the loss of cells associated with fibrosis,
      the influence of PFD on apoptosis-regulatory genes in a manner that reduces
      apoptosis may explain some of its antifibrotic properties.

PMID- 15729168
TI  - Intrahepatic biliary strictures without hepatic artery thrombosis after liver
      transplantation: an analysis of 1,113 liver transplantations at a single center.
AB  - BACKGROUND: Intrahepatic biliary strictures (IHBS) without hepatic artery
      thrombosis (HAT) is a serious complication and known to increase the risk of
      graft failure after liver transplantation. This manuscript describes the
      incidence, risk factors, clinical pictures, management, and outcomes. METHODS:
      Between 1994 and 2002, 1,113 liver transplantations were performed in 974 adult
      patients. Data was retrospectively analyzed in terms of incidence, risk factors,
      clinical pictures (type of strictures), management (radiologic, surgical
      management), and outcomes. RESULTS: Sixteen (1.4%) grafts had IHBS without HAT.
      Specific risk factors were not identified from donors or recipients. However,
      ischemic factors from the donors were suspected from non-heart-beating donors
      (n=1) and cardiac-arrest donors (n=2). Three types of IHBS were identified: (1)
      diffuse type (n=7), (2) bilateral proximal type (n=7), and (3) unilateral type
      (n=2). Overall success rate of radiologic interventions was 31.3% (5/16). Of the
      11 patients who did not improve, 6 died: diffuse type (3/7, 42.9%), bilateral
      type (3/7, 42.9%), and unilateral (0/2, 0%). Three patients had
      retransplantation, and two patients are waiting retransplantation. The majority
      of the IHBS were diffuse or bilateral (14/16, 87.5%), and rate of the graft
      failure was high (10/14, 71.4 %). Overall graft survival of IHBS was lower than
      that without IHBS (P=0.025). CONCLUSIONS: The majority of the IHBS without HAT
      were of a diffuse or bilateral proximal type. Patients with diffuse or bilateral
      proximal type have a low success rate from radiologic intervention and may
      benefit from early retransplantation.

PMID- 15729170
TI  - Posttransplant diabetes mellitus and atherosclerotic events in renal transplant
      recipients: a prospective study.
AB  - BACKGROUND: Posttransplant diabetes mellitus (PTDM) is a frequent complication in
      renal-transplant recipients (RTRs). We conducted a prospective study to assess
      the potential role of PTDM in the development of atherosclerotic events (AE) in
      RTRs. METHODS: Three hundred fifty-seven consecutive RTRs were enrolled in this
      study. The incidence of various AE were assessed with respect to the presence of
      PTDM and a number of cardiovascular (CV) risk factors. RESULTS: The patients were
      followed for a mean duration of 60+/-14 months. Thirty-nine (11%) patients had
      PTDM. Fifty AE occurred in 48 (13.4%) patients. Although AE were more frequent in
      RTRs with PTDM compared with nondiabetic patients (33% vs. 8.8%; P=0.007), PTDM
      was only modestly associated with AE in the multivariate Cox regression analysis
      (relative risk [RR] 1.34; 95% confidence interval [CI], 1.04-2.18), mostly caused
      by significant interactions between PTDM and three confounding variables that
      were independently associated with AE: age, serum C-reactive protein (CRP) level,
      and serum high-density lipoprotein cholesterol concentration. Patients with high
      levels of homocysteine showed a significantly increased risk of AE (RR 4.67; 95%
      CI 1.82-15.87), as did those with high serum levels of CRP (RR 2.57; 95% CI 1.57
      6.23). CONCLUSIONS: Our study shows a significant association between PTDM and
      AE. Nevertheless, a large amount of the excess risk of posttransplant diabetic
      RTR is explained by the coexistence of other CV risk factors. Moreover, high
      serum levels of CRP and hyperhomocystinemia were found to be among the
      nontraditional factors contributing to AE in our patients.

PMID- 15729169
TI  - Successful pancreas preservation by a perfluorocarbon-based one-layer method for
      subsequent pig islet isolation.
AB  - BACKGROUND: The oxygenation of human pancreas by the two-layer method (TLM)
      during cold storage was recently established for clinical islet transplantation.
      Simplification of TLM would facilitate the application of perfluorocarbon (PFC)
      as a regularly used preservation solution for subsequent islet transplantation.
      The present study examined whether PFC can be used in a one-layer method (OLM)
      for long-term pancreas preservation before isolation of adult pig islets.
      METHODS: Resected pancreases were intraductally flushed with cold University of
      Wisconsin solution and immediately processed (n=6) or subjected to 7-hour storage
      by OLM (n=8) or TLM (n=10). Subsequently, pancreases were intraductally distended
      with collagenase NB-8 supplemented with neutral protease. Isolation and
      purification were performed as previously described. RESULTS: Compared with
      unstored pancreases (3,670+/-740 islet equivalents [IEQ]) purified islet yield in
      TLM-stored organs (2,080+/-290 IEQ, P<0.05) was significantly decreased in
      contrast with OLM-preserved pancreases (3,110+/-520 IEQ, NS). No differences were
      observed between groups regarding purity (>90%), trypan-blue exclusion (>95%),
      adenosine triphosphate content, and mitochondrial viability of islets.
      Stimulation index during static glucose incubation (20 vs. 2.8 mm) was decreased
      after storage by TLM (1.81+/-0.20, P<0.05) but not by OLM (2.27+/-0.57) if
      compared with unstored pancreases (2.47+/-0.36). However, transplantation into
      diabetic nude mice resulted in sustained normoglycemia of recipients of either
      group until nephrectomy of graft-bearing kidneys was performed. CONCLUSIONS: This
      study demonstrates that PFC alone can be used in a one-layer procedure for
      successful pig-pancreas preservation. This simplification can facilitate the
      broad application of PFC as pancreas preservation solution without reducing its
      benefits demonstrated by TLM.

PMID- 15729171
TI  - Abundance of interstitial eosinophils in renal allografts is associated with
      vascular rejection.
AB  - BACKGROUND: The authors investigated the possible relevance of significant
      interstitial graft eosinophilic infiltrate (SIGEI) to the pathologic diagnosis of
      renal transplants. METHODS: The authors performed a clinical and pathologic
      review of 29 consecutive patients with renal allograft failure and nephrectomy.
      As a result of their size, such specimens are more conducive than biopsies to the
      investigation of large blood vessels. SIGEI was diagnosed when eosinophils
      represented 10% or more of the interstitial inflammatory infiltrate. Vascular
      rejection was graded according to the Banff criteria. Risk for allergic
      interstitial nephritis and immunosuppression at the time of the nephrectomy-high
      dose, minimal, or none-was determined from the clinical history. RESULTS: SIGEI
      was observed in 13 of the 29 patients and was absent in 16. Vascular (Banff type
      II) rejection was present in 11 of 13 cases with SIGEI and in 9 of 16 cases
      without SIGEI. The relation between SIGEI and Banff type II rejection was
      statistically significant: in 14 patients on high-dose immunosuppression,
      vascular rejection was present in all 5 cases with SIGEI, whereas in the 9 grafts
      without SIGEI, only 3 had vascular rejection (P=0.04). The authors did not find
      an association between SIGEI and risk for iatrogenic interstitial nephritis:
      SIGEI was seen in only 4 of 15 patients with high or moderate iatrogenic risk.
      CONCLUSIONS: In this series of allograft nephrectomies, SIGEI was significantly
      associated with vascular rejection (Banff type II) but not with risk of allergic
      iatrogenic nephritis, suggesting that the presence of SIGEI may be a helpful
      criterion in the pathologic diagnosis of renal allografts.

PMID- 15729173
TI  - The influence of immunomodulatory diets on transplant success and complications.
AB  - BACKGROUND: Animal studies have shown that dietary supplementation with arginine
      and lipids containing the omega-3 and omega-9 fatty acids prolong allograft
      survival in animals receiving a short course of low-dose cyclosporine. They also
      reduce cardiovascular complications and infections in humans. METHODS: Adult
      renal transplant patients receiving standard immunosuppression were stratified
      according to gender, diabetic state, donor source (LD or CD), and first versus
      repeat transplant, and randomized to receive or not receive supplemental arginine
      and canola oil (containing both omega-3 and omega-9 fatty acids) twice daily.
      Patients were followed for a minimum of 3 years. RESULTS: Seventy-six patients
      were randomized to the supplement group (S) and 71 patients to the control group
      (C). Intent-to-treat analysis revealed that S patients had fewer post-30 day
      first rejection episodes (5.4%) when compared with the C group (23.7%) (P=0.01)
      and fewer post-30 day episodes of calcineurin inhibitor (CNI) drug toxicity (9.2%
      vs. 35.3%, P=0.003). S patients developed new onset diabetes mellitus (NODM) less
      frequently by 3 years (2.3% vs. 14.5%, P=0.04), had fewer cardiac events (5.0%
      vs. 17.1%, P=0.05), and fewer episodes of sepsis (6.5% vs. 18.7%, P=0.05).
      CONCLUSIONS: Dietary supplementation with L-arginine and canola oil is a safe,
      inexpensive, and unique treatment, which is associated with decreased rejection
      rates and CNI toxicity after the first month in renal transplant patients. Due to
      reductions in NODM and cardiac events, long-term benefits for patient survival
      may be particularly important.

PMID- 15729172
TI  - Augmentation of type-1 polarizing ability of monocyte-derived dendritic cells
      from chronically immunosuppressed organ-transplant recipients.
AB  - BACKGROUND: Chronic immunosuppressive (IS) therapy impairs normal T-cell immune
      surveillance and may predispose to opportunistic infections and malignancies that
      represent life-threatening complication of solid-organ transplantation (SOTx).
      Our study was designed to ascertain the impact of chronic in vivo administration
      of IS on the ability of monocyte-derived dendritic cells (MoDC) to differentiate,
      mature, and function ex vivo. The potential of these cells to be implemented for
      DC-based adoptive immunotherapy was also considered. METHODS: MoDCs were
      propagated by conventional procedures, their phenotype was analyzed by flow
      cytometry, and their function was assessed by mixed leukocyte reaction, enzyme
      linked immunoadsorbent assay, and ELISPOT assays. Nuclear translocation of
      nuclear factor (NF)-kB was analyzed by electrophoretic mobility shift assay.
      RESULTS: Circulating DC1s in peripheral blood were reduced in SOTx patients.
      MoDCs generated from patients displayed higher endocytic activity versus normal
      DCs, indicating their comparative immaturity. Patients' DCs exposed to pro
      inflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, and
      IL-6) were less able to mature, to stimulate recall antigen (Ag)- or allo-Ag
      induced proliferation responses, or to secrete IL-12p70. These deficiencies were
      associated with a decrease in NF-kB translocation. In contrast, combination of
      pro-inflammatory cytokines and interferon (IFN)-gamma (a Th1-polarizing factor)
      augmented patients' DC1-type function and IL-12p70 production by way of an NF-kB
      independent mechanism. CONCLUSIONS: Chronic IS restrains DC differentiation,
      maturation, and function at a transcriptional level; however, type-1 polarizing
      potential of patients' DC1 can be augmented ex vivo by a two-signal stimulation
      provided by pro-inflammatory cytokines and IFN-gamma. These results may have
      implications for DC-based immunotherapy of malignancies in the transplantation
      setting.

PMID- 15729174
TI  - Mycophenolate mofetil substitution for cyclosporine a in renal transplant
      recipients with chronic progressive allograft dysfunction: the "creeping
      creatinine" study.
AB  - BACKGROUND: This study determined whether cyclosporine A (CsA)-treated renal
      allograft recipients with deteriorating renal function ("creeping creatinine")
      secondary to chronic allograft nephropathy (CAN) benefit from the addition of
      mycophenolate mofetil (MMF) to their immunosuppressive regimen, followed by
      withdrawal of CsA. METHODS: In a controlled, open, multicenter study, CsA-treated
      renal allograft recipients with progressively deteriorating renal function were
      randomized to have their CsA discontinued with the concomitant addition of MMF to
      their regimen (group A) or to continue treatment with CsA (group B). The primary
      endpoint was the response rate over the 6-month period after withdrawal of CsA in
      group A or the equivalent time in group B. Response was defined as a
      stabilization or reduction of serum creatinine (SCr), as evidenced by a
      flattening or positive slope of the 1/SCr plot and no graft loss. Secondary
      endpoints included the incidence of acute rejection, graft and patient survival,
      and changes in selected metabolic parameters. RESULTS: The response rate in the
      primary intent-to-treat population (n=122) was 58% (36/62) in group A versus 32%
      (19/60) in group B (P=0.0060). The corresponding percentages of responders in the
      per-protocol population (n=107) were 60% (36/60) and 26% (12/47), respectively
      (P=0.0008). There were no acute rejections in group A during the study period.
      Patients in this group also experienced a significant decrease in total
      cholesterol. CONCLUSIONS: In patients with progressively deteriorating renal
      function secondary to CAN, addition of MMF followed by withdrawal of CsA results
      in a significant improvement in transplant function without the risk of acute
      rejection.

PMID- 15729175
TI  - Cutaneous adverse events in renal transplant recipients receiving sirolimus-based
      therapy.
AB  - BACKGROUND: Sirolimus is an immunosuppressive drug recently developed for organ
      transplantation. Its mechanism of action, independent of calcineurin, is
      different from that of cyclosporine and tacrolimus, two calcineurin inhibitors
      (CIs). Because the toxicity of CIs is partly the result of calcineurin blockade,
      sirolimus exhibits a different toxicity profile. In this study, we evaluated the
      profile, frequency, and severity of cutaneous adverse events in renal transplant
      recipients receiving sirolimus-based therapy. PATIENTS AND METHODS: A systematic
      and in-depth evaluation of skin, mucous membranes, nails, and hair was performed
      in 80 renal transplant recipients receiving sirolimus-based therapy. The mean
      duration of the graft was 6 years and of sirolimus treatment was 18 months.
      Mycophenolate mofetil and steroids were combined with sirolimus for 74 patients.
      Sirolimus was used as first immunosuppressive therapy for 36 patients, and 44
      patients were switched from CIs to sirolimus. RESULTS: Seventy-nine patients
      (99%) experienced cutaneous adverse events. Twenty patients (25%) demonstrated
      serious adverse events, and six patients (7%) stopped sirolimus during the 3
      months after the study because of cutaneous events. The most frequent of these
      were pilosebaceous apparatus involvement, including acne-like eruptions (46%),
      scalp folliculitis (26%), and hidradenitis suppurativa (12%); edematous
      complaints, including chronic edemas (55%) and angioedema (15%); mucous membrane
      disorders, including aphthous ulceration (60%), epistaxis (60%), chronic
      gingivitis (20%), and chronic fissure of the lips (11%); and last, nail disorders
      including chronic onychopathy (74%) and periungual infections (16%). CONCLUSIONS:
      Skin disorders are frequent in renal transplant recipients receiving sirolimus as
      a long-term therapy. Despite the usually mild nature of skin events, they are
      often the reason for stopping sirolimus.

PMID- 15729176
TI  - Liver transplantation for hepatocellular carcinoma in cirrhosis: is clinical
      tumor classification before transplantation realistic?
AB  - BACKGROUND: The decision of whether to proceed with transplantation in patients
      with hepatocellular carcinoma (HCC) in cirrhosis is based on clinical and imaging
      findings. The purpose of our study was to evaluate the accuracy of the current
      system. MATERIALS AND METHODS: We evaluated data of 70 patients with HCC who
      underwent liver transplantation (LTx) at our center. We specifically analyzed the
      correlation between preoperative imaging studies and postoperative
      anatomopathologic findings. Tumor-node-metastasis, Milan, and University of
      California San Francisco (UCSF) classifications were used. Patients were divided
      in 2 groups: (1) Patients undergoing live-donor LTx (LDLTx, n=35) and (2)
      patients undergoing cadaveric LTx (CLTx, n=35). RESULTS: Only 10 (14.3%) of the
      70 patients considered had tumor diameter that was correctly identified by
      pretransplant radiologic examinations. Twenty-four (34.2%) patients had correct
      identification of the number of tumors present. Fifty (71.4%) patients had
      incorrect measurements of tumor diameter of more than 1 cm. Sensitivity of
      radiologic imaging was especially poor for tumors between 1 and 2 cm and less
      than 1 cm (21% and 0%, respectively). Best accuracy of 60% was found for both the
      Milan and UCSF criteria. No significant difference was found between the two
      patient groups concerning the accuracy of the various systems/criteria of
      classification. CONCLUSIONS: Current imaging techniques have a high incidence of
      false-negative and false-positive results when evaluating HCC in cirrhosis. A
      critical appraisal of patient characteristics together with great caution when
      interpreting imaging studies is recommended to determine candidacy for
      transplantation.

PMID- 15729177
TI  - Augmented induction of CD4+CD25+ Treg using monoclonal antibodies to CD200R.
AB  - BACKGROUND: CD200 is a transmembrane protein delivering immunoregulatory signals
      after engagement of CD200R. A family of CD200Rs exist (CD200R1-4) with different
      tissue expression and functional activity. In the presence of anti-CD200R2/3
      monoclonal antibodies (mAbs), bone-marrow cells cultured in the presence of
      (interleukin [IL]-4+granulocyte-macrophage colony-stimulating factor)
      differentiate into dendritic cells (DCs), which induce CD4CD25Treg. The effect of
      these mAbs on Treg induced in anti-CD3 activated thymocyte cultures is unknown.
      METHODS: BL/6 bone-marrow cells were cultured with GMC-SF and IL-4 in the
      presence/absence of anti-CD200Rs to generate DCs that induced Treg in C3H lymph
      node T cells. Treg were also induced in anti-CD3/CD28-activated C3H thymocytes.
      Treg activity was assayed by (1) suppression of mixed leukocyte culture (MLC) in
      cultures using C3H stimulator spleen cells and BL/6 stimulator cells, and (2) by
      expression of the transcription factor, Foxp3. RESULTS: Addition of anti
      CD200R2/3 mAbs (but not anti-CD200R1) to bone-marrow cultures led to generation
      of DCs that induced a CD4CD25 (Treg) population inhibiting MLCs (C3H cells
      stimulated with C57BL/6 cells) in a cytotoxic T-lymphocyte-associated antigen
      (CTLA)-4 and transforming growth factor (TGF)-beta-dependent manner. Anti
      CD200R2, but not anti-R1/R3, augmented induction of Foxp3-expressing Treg from
      anti-CD3/CD28 activated thymocytes. Suppression in MLCs by anti-CD200R1 mAbs was
      dependent on IL-10 and TGF-beta. CONCLUSIONS: Unlike anti-CD200R1, anti-CD200R2
      both promotes development of DCs with capacity to induce Treg and directly
      augments thymocyte production of Treg.

PMID- 15729178
TI  - Novel mediators of FTY720 in human lymphocytes.
AB  - FTY720 (FTY), a novel immunosuppressive drug, can be distinguished from other
      immunosuppressive drugs by a completely different mechanism of action. FTY
      induces altered lymphocyte trafficking, leading to peripheral blood lymphopenia
      and to increased lymphocyte counts in lymph nodes. FTY mediates its immune
      modulating effects by binding to sphingosine 1-phosphate receptors expressed on
      lymphocytes. In an attempt to identify mediators of the FTY-induced signal
      transduction, we used a proteomic approach. FTY-treated peripheral blood
      lymphocytes (PBLs) were investigated for the expression of 622 proteins. We
      identified 15 differentially expressed proteins in PBLs possibly related to FTY
      action. As indicated by protein function, several identified proteins could be
      linked to the cytoskeleton/cell motility, to cell adhesion, and vesicle
      trafficking. No changes were found concerning the expression of various apoptosis
      regulators as well as the immunophilins FKBP12 and calcineurin. Our data suggest
      that FTY affects cytoskeleton rearrangements, cell adhesion, and vesicle
      trafficking/sorting in human PBLs.

PMID- 15729179
TI  - Replacement kidney lipomatosis after renal transplantation.
AB  - Renal sinus lipomatosis consists of abnormal fatty proliferation of the renal
      sinus, hilus, and perirenal spaces. Its pathogenesis is unknown, although it is
      generally associated with aging, renal atrophy, and long-standing chronic
      inflammation or urinary tract infection. Although this condition is rare, it may
      be important to recognize it in renal transplant recipients. We describe three
      cases of replacement kidney lipomatosis that occurred after cadaveric renal
      transplantation and discuss the possible differential diagnosis of this
      condition.

PMID- 15729180
TI  - Tacrolimus pharmacogenetics: the CYP3A5*1 allele predicts low dose-normalized
      tacrolimus blood concentrations in whites and South Asians.
AB  - Previously, we demonstrated that the dose-normalized tacrolimus blood
      concentration after renal transplantation was associated with a single nucleotide
      polymorphism (SNP) in the CYP3AP1 gene, probably through linkage with an SNP in
      the CYP3A5 gene. Individuals with at least one CYP3A5*1 allele synthesize CYP3A5
      and CYP3A5*3/*3 homozygotes do not. We now present results with direct typing of
      the CYP3A5 genotype for this group of 180 kidney-only transplant recipients from
      a single center. South Asian and white patients with at least one CYP3A5*1 allele
      achieved twofold lower dose-normalized tacrolimus blood concentrations compared
      with CYP3A5*3/*3 homozygotes, confirming our previous findings for the CYP3AP1
      SNP. There was a significant delay in achieving target blood concentrations in
      those with at least one CYP3A5*1 allele. Determination of the CYP3A5*1/*3
      genotype could be used to predict the tacrolimus dose requirement and, given
      incomplete linkage, would be better than determination of the CYP3AP1 genotype.

PMID- 15729181
TI  - Revascularization of the gastroduodenal artery in a pancreas allograft from a
      donor with a replaced right hepatic artery.

PMID- 15729182
TI  - The diffusion parameter in magnetic resonance: physics, techniques, and
      semeiotics.

PMID- 15729183
TI  - Screening of lung cancer with low dose spiral CT: results of a three year pilot
      study and design of the randomised controlled trial ''Italung-CT''.
AB  - PURPOSE: To report the results of a three-year observational pilot study of lung
      cancer screening with low dose computed tomography (CT) and to present the study
      design of a randomised clinical trial named as ''Italung-CT''. MATERIALS AND
      METHODS: Sixty (47 males and 13 females, mean age 64+/-4.5 years) heavy smokers
      (at least 20 packs-year) underwent three low-dose spiral CT screening tests one
      year apart on a single slice or multislice CT scanner. Indeterminate nodules were
      managed according to the recommendations of the Early Lung Cancer Action Project.
      RESULTS: and Indeterminate nodules were observed in 33 (55%) of the subjects (60%
      at the baseline screening test, 24% at the first annual test and 16% at the
      second annual test). The size of the largest indeterminate nodule was <5 mm in
      diameter in 20 subjects, 10 of whom showed the nodule at the baseline test. Forty
      five subjects (75%) completed the first annual test and 42 (70%) the second
      annual test. One (1.6%) prevalent lung cancer (adenosquamous carcinoma) and one
      (2.2%) incident lung cancer (small cell cancer at the first annual examination)
      were observed, as well as a pulmonary localisation of Hodgkin's lymphoma (at the
      second annual test). In addition, one subject underwent lung surgery for a
      chondromatous hamartoma. CONCLUSIONS: The results of the pilot study are
      substantially in line with those of other observational studies of greater sample
      size. This justifies optimism about the reliability of the results in the
      screened arm of the ''Italung CT'' trial which has just begun.

PMID- 15729184
TI  - Early smoking-induced lung lesions in asymptomatic subjects. Correlations between
      high resolution dynamic CT and pulmonary function testing.
AB  - PURPOSE: To evaluate the prevalence and significance of the pathological effects
      of cigarette smoking on the lung and the sensitivity of high-resolution CT (HRCT)
      in the recognition of early smoking-induced lesions in asymptomatic former or
      current smokers. MATERIALS AND METHODS: We performed a prospective and
      consecutive analysis of 36 volunteers (16 males, 20 females), 10 non-smokers (3
      males; 7 females) and 26 smokers (13 males; 13 females / 17 current smokers; 9
      former smokers), all asymptomatic and with normal respiratory flows. These
      subjects underwent lung function testing and HRCT, after providing written
      informed consent for the study. The HRCT scans were obtained at three pre
      selected levels (aortic arch, tracheal carina and venous hilum). The same scans
      were obtained in post-expiration phase. At the level of the apical segmental
      bronchus of the right upper lobe, we measured on the monitor wall thickening, and
      the total and internal diameters using the techniques reported in literature.
      Each study was independently evaluated by two radiologists that were blinded to
      all clinical and functional data; they also evaluated the presence, prevalence
      and type of emphysema, areas of patchy hyperlucency and oligoemia in the
      inspiration phase and areas of expiratory air trapping. The extension was
      evaluated with the visual score method. The data obtained were analysed with the
      Windows SPSS package for statistical analysis. RESULTS: The two groups (non
      smokers and smokers) showed significant differences in some functional tests such
      as FEV1 (p<0.005) and Tiffeneau index (p<0.005), which were lower in current
      smokers or former-smokers, although still within the normal range. The HRCT study
      did not show areas of emphysema or air trapping in non smokers. In the smokers'
      group, air trapping was observed in 30.7% of cases: 33.3% former-smokers and
      29.4% current smokers (mean extension was 21.36% in former smokers and 9.48% in
      current smokers). Mean extension in the smokers' group was 13.94%. Pulmonary
      emphysema was found in 34.6% of cases in the smokers' group: 33.3% former-smokers
      and 35.2% current-smokers. Emphysema was prevalent in the upper lobes (88.8%).
      Mean extension was 8.76% in the former smokers group and 18.81% in current
      smokers, with a total mean extension of 15.47% in the smokers' group.
      Statistically, there was a significant difference between non-smokers and smokers
      as regards emphysema extension and expiratory air trapping (p=0.034 and p=0.050,
      respectively). The smokers' group had a significantly wider diameter of the
      apical segmental bronchus of the right upper lobe than the controls. There was no
      significant statistical correlation between this dilatation and the emphysema
      score (r=0.051; p=0.81). The entity of smoking history did not correlate with
      emphysema extension or air trapping or with the size of the apical segmental
      bronchus of the right upper lobe. CONCLUSIONS: Our study demonstrates that HRCT
      is more sensitive and specific than commonly-used functional tests for the
      evaluation of initial emphysema in asymptomatic smokers. We observed expiratory
      air trapping only in the smokers' group, and only of the lobular type, without
      evidence of disease in inspiratory scans. Among the smokers and former-smokers,
      air trapping was found in 30.7% of subjects, with a mean extension lower than
      10%. Our results therefore suggest that, even in asymptomatic subjects,
      expiratory air trapping is probably pathological and, once bronchial asthma has
      been excluded, it may be related to cigarette smoking and indicate early
      inflammatory bronchiolar damage. HRCT may therefore be regarded as a useful tool
      in the early diagnosis of smoking-related lung disease.

PMID- 15729185
TI  - Evaluation of effectiveness of a computer system (CAD) in the identification of
      lung nodules with low-dose MSCT: scanning technique and preliminary results.
AB  - PURPOSE: Evaluation of the effectiveness of computer-aided diagnosis (CAD) in the
      identification of pulmonary nodules. MATERIALS AND METHODS: Two observers (A1,
      A2) with different levels of experience independently evaluated 20 chest MSCT
      studies with and without the aid of a CAD system (LungCheck, R2 Technology, Inc).
      The study parameters were as follows: 140 kVs, 40 mAs, collimation 4 x 1 mm,
      slice thickness 1.25 mm, reconstruction interval 1.0 mm. The observers analysed
      the images with and without CAD and evaluated: 1) nodule size (longer axis); 2)
      number and location of nodules; 3) reading time for each observer. The gold
      standard was represented by the evaluation of both readers in consensus with the
      aid of the CAD system. RESULTS: Without CAD support the two readers identified 77
      (A1) and 79 (A2) nodules and with CAD 81 (A1) and 82 (A2) nodules. Working in
      consensus the two observers identified 81 nodules without the aid of the CAD and
      84 nodules with the aid of CAD. Total number of nodules identified by CAD was
      104, 25 of which were false positive and 5 false negative. The average reading
      time with the aid of the CAD decreased by as much as 40% for both the observers.
      CONCLUSIONS: The preliminary results of our study suggest that the CAD technique
      is an accurate automatic support tool in the identification of pulmonary nodules.
      It reduces reading time and automatically supplies the size, volume, density and
      number of nodules, thus being useful both in screening programmes and in the
      follow-up of cancer patients, in whom comparison of the images is particularly
      difficult.

PMID- 15729186
TI  - Multidetector CT: a new gold standard in the diagnosis of pulmonary embolism?
      State of the art and diagnostic algorithms.
AB  - PURPOSE: From the early 90s, spiral CT technology has considerably changed the
      diagnostic capability of Pulmonary Embolism (PE), giving a direct vision of
      intravascular thrombi. Further technological progress has strengthened its
      diagnostic impact leading to an essential role in clinical practice. The advent
      of Multi-Detector CT (MDCT) has subsequently increased the reliability of this
      technique to the point of undermining the role of pulmonary angiography as the
      gold standard and occupying a central position in diagnostic algorithms. The aim
      of this paper is to appraise this evolution by means of a meta-analysis of the
      relevant literature from 1995 to 2004. RESULTS: The review of the literature
      showed the sensitivity and specificity of CT to have increased from 37-94% and 81
      100% (single-detector CT) to 87-94% and 94-100% (4-channel multidetector CT),
      especially thanks to the possibility of depicting subsegmental clots, with an
      interobserver agreement of 0.63-0.94 (k). CONCLUSIONS: CT is one of the most
      reliable and effective methods in the diagnosis is PE, with the advantage of
      being extremely fast and providing alternative diagnoses. Recent improvements in
      MDCT technology confers the highest value of diagnostic accuracy with respect to
      other imaging modalities such as scintigraphy, angiography, MRI, D-dimer assay
      and Doppler US.

PMID- 15729187
TI  - Magnetic resonance imaging in the evaluation of the pericardium. A pictorial
      essay.
AB  - Magnetic resonance (MR) is an ideal technique for the evaluation of the
      pericardium since it enables the combination of high resolution anatomical images
      of the pericardial layers with functional information concerning the impact of
      pathology on diastolic heart function and cardiac filling in particular. In
      comparison with echocardiography, which remains the first choice technique for
      the study of the pericardium, MR provides larger fields of view allowing the
      visualisation of the entire chest, higher spatial and contrast resolution and
      greater reproducibility. The technique becomes particularly useful when
      ultrasound imaging does not provide adequate diagnostic information or requires
      further characterisation; ''non-echoic'' patients, loculated pericardial
      effusions, focal thickening of the layers and pericardial masses are usually
      better assessed with MR. The method also provides valuable diagnostic information
      for establishing the diagnosis of constrictive pericarditis and to differentiate
      this condition from restrictive cardiomyopathy. The aim of this paper is to
      present the role of MR imaging in the assessment of a patient with suspected
      pericardial disease, and discuss the MR technique, anatomy and the main
      pathological conditions.

PMID- 15729188
TI  - Non cardiopatic and cardiopatic beta thalassemic patients: quantitative and
      qualitative cardiac iron deposition evaluation with MRI.
AB  - PURPOSE: Cardiomyopathy is one of the major complications of b thalassaemia major
      as a result of transfusional iron overload. The aim of our study is to evaluate
      with MR if there is any difference of iron deposition signal intensity (SI) or
      distribution between non-cardiopathic and cardiopathic thalassaemic patients in
      order to establish if there is a relationship between cardiopathy and iron
      deposition. MATERIALS AND METHODS: We studied 20 patients affected by b
      thalassaemia major, of whom 10 cardiopathic and 10 non-cardiopathic, and 10
      healthy volunteers as control group. Serum ferritin and left ventricular ejection
      fraction were calculated in thalassaemic patients. All patients were examined
      using a 1.5 MR unit with ECG-gated GE cine-MR T2*-weighted, SE T1-weighted and GE
      T2*-weighted sequences. In all cases, using an adequate ROI, the myocardial and
      skeletal muscle signal intensity (SI), the myocardial/skeletal muscle signal
      intensity ratio (SIR) and the SI average of the myocardium and skeletal muscle
      were calculated for every study group. The qualitative evaluation of iron
      deposition distribution was independently performed by three radiologists who
      analyzed the extension, the site and the morphology of iron deposition on the MR
      images and reported their observations on the basis of a four-level rating scale:
      0 (absent), 1 (limited), 2 (partial), 3 (widespread deposition). The result of
      quantitative and qualitative evaluations were analysed with statistical tests.
      RESULTS: Cardiac iron deposition was found in 8/10 non-cardiopathic thalassaemic
      patients and in all cardiopathic thalassaemic patients. We noticed a significant
      SI difference (p>0.05) between the healthy volunteer control group and the
      thalassaemic patients with iron deposition, but no significant SI difference in
      iron deposition between non-cardiopathic and cardiopathic thalassaemic patients
      in the areas evaluated. The qualitative evaluation revealed a different
      distribution of iron deposition between the two thalassaemic groups, with more
      widespread distribution in cardiopathic patients. CONCLUSIONS: We found cardiac
      iron deposition also in non-cardiopathic b thalassaemic patients and a
      qualitative difference in cardiac iron distribution between non-cardiopathic and
      cardiopathic patients. The qualitative evaluation of cardiac iron deposition was
      useful for an easier classification of the disease, bypassing the SI quantitative
      value which is affected by the extremely uneven distribution of iron deposition
      and by the sampling technique used. MR evaluation of non-cardiopathic
      thalassaemic patients may be useful to evaluate early iron deposition and to
      establish the most suitable chelation therapy.

PMID- 15729190
TI  - 3D angiography in the evaluation of intracranial aneurysms before and after
      treatment. Initial experience.
AB  - PURPOSE: The aim of the study is to evaluate the advantages of 3D angiography as
      compared to 2D angiography in assessing intracranial aneurysms before and after
      treatment and, in particular, in selecting and planning the correct treatment.
      MATERIALS AND METHODS: Thirty intracranial aneurysms were retrospectively
      reviewed before and after treatment. The study population consisted of 12 men and
      18 women (age range: 35-77 years; mean age: 58 years). Eighteen aneurysms were
      treated surgically, 10 endovascularly and 2 with combined treatment. The 2D and
      3D findings before and after treatment were compared, and the pre-treatment
      angiographic images were compared with surgical findings. The following
      parameters were assessed and compared: aneurysmal sac and neck size, vascular
      involvement and evaluation of post-treatment residual mass. RESULTS: On the 2D
      DSA images, visualisation of the sac and neck was optimal in 45% and 15% of
      cases, adequate in 10% and 35% of cases and inadequate in 5% and 50% of cases,
      respectively. On the 3D DSA images, visualisation of the sac and neck was optimal
      in 100% of cases. Three-dimensional DSA was able to detect 8 aneurysms with
      vessel involvement in all cases (100%). Of these, four (50%) went undetected on
      2D DSA; in two cases, two-dimensional DSA erroneously detected the presence of
      vascular involvement (false positive). Three-dimensional angiography proved
      superior to 2D angiography in the evaluation of the residual aneurysms treated
      with clipping. Finally, 3D DSA was able to reduce the number of radiographic
      projections, the quantity of contrast medium, the time and associated risks
      necessary for a precise evaluation of the aneurysm. CONCLUSIONS: In our first
      experience, 3D DSA proved useful in reducing the risks and diagnostic time as
      well as in selecting and planning the treatment. Moreover, it improved the
      operating conditions of both surgical and endovascular treatment. Technological
      advances in this field will enable the optimisation of the technique in terms of
      anatomical detail and reconstruction time.

PMID- 15729189
TI  - Diagnostic accuracy of 16-row multislice CT angiography in the evaluation of
      coronary segments.
AB  - PURPOSE: To evaluate the diagnostic accuracy of 16-row multislice spiral computed
      tomography coronary angiography (16-MSCT-CA) for the non-invasive assessment of
      significant coronary artery stenosis. MATERIALS AND METHODS: We enrolled 40
      patients (36 male, aged 59+/-11 yrs) with suspected obstructive coronary artery
      disease and a heart rate <65 bpm during the scan. The 16-MSCT-CA (Sensation 16,
      Siemens, Forchheim, Germany) was performed with electrocardiographically-gated
      technique after the intravenous administration of 100 ml of iodinated contrast
      material followed by a saline bolus chaser. The scan parameters were: collimation
      16 x 0.75 mm, rotation time 0.42 s, feed/rot. 3 mm (pitch 0.25), 120 kVp, 500
      mAs. All coronary segments = or >2 mm in diameter were evaluated by two
      independent observers for the presence of significant coronary artery stenosis (=
      or >50%). Consensus reading was compared to quantitative coronary angiography.
      RESULTS: The average heart rate was 55+/-6 bpm. Of the 428 segments of = or >2.0
      mm diameter 92 were significantly diseased. Without exclusion of any branches
      (428), the sensitivity, specificity, positive, and negative predictive values to
      identify = or >50% obstructed segments were 95.7% (88/92), 95.8% (322/336), 86.3%
      (88/102), and 98.8% (322/326), respectively. No occluded left main, left anterior
      descending, circumflex or right coronary artery segments remained undetected.
      CONCLUSIONS: 16-MSCT-CA in a selected low-heart-rate patient population provides
      high diagnostic accuracy in the evaluation of significant coronary artery
      stenosis.

PMID- 15729191
TI  - Three-dimensional rotational angiography of the carotid arteries with high-flow
      injection from the aortic arch. Preliminary experience.
AB  - PURPOSE: Three-Dimensional Rotational Angiography (3DRA) is a new technique based
      on a rotational angiographic acquisition able to display arterial vessels in a 3D
      rendering mode. The system was mainly developed for neuroradiological evaluations
      but preliminary extracranial experiences have also been reported. The aim of our
      work was to compare the results of three-dimensional angiography of the carotid
      arteries done with high-flow injection of contrast medium from the aortic arch
      with the results of selective angiography. MATERIALS AND METHODS: Twenty patients
      underwent digital angiography of the supra-aortic vessels in order to quantify a
      stenosis of the carotid bifurcations previously detected at Doppler Ultrasound.
      Examinations were performed with the Philips Integris Allura system provided with
      the rotational angiography (RA) tool connected to a workstation for three
      dimensional reconstruction able to display vessels in a 3D fashion (Volume
      Rendering, Gradient Rendering, Shaded Surface Display), automatically remove bone
      structures (cervical spine, calcified plaque, etc.) and perform an automatic
      analysis of the vessel diameter and surface area at the point of major stenosis
      and in the disease-free vessel segments above and below. The carotid evaluation
      was done either with selective catheterization and the two standard AP and LL
      projections and with RA after contrast medium injection from the aortic arch
      followed by 3D reconstruction. RESULTS: The comparison of the selective
      angiography and three-dimensional images was possible in 37 out of 40 carotid
      bifurcations (3 internal carotid arteries were occluded) and a good diagnostic
      quality was obtained in 35 out of 37 cases with an high correlation in the degree
      of stenosis. In 2/37 cases with calcified plaques the degree of stenosis was
      effectively demonstrated only after electronic subtraction of the calcified
      component of the plaque. CONCLUSIONS: The technique we propose proved to be
      feasible in all cases with a good correlation in the quantification of the degree
      of stenosis. The practical advantage of our technique is the almost complete
      exclusion of risks of neurological complications due to selective
      catheterization, and reduced examination time.

PMID- 15729192
TI  - Femoral haemostosis with Vasoseal ES: experience in 150 patients.
AB  - PURPOSE: The aim of this study is to assess the effectiveness and safety of the
      use of Vasoseal ES collagen plug in heavily anticoagulated patients with high
      risk of complications at the vascular access site who had undergone vascular
      radiological intervention. MATERIALS AND METHODS: Between January 2002 and March
      2003 180 consecutive transfemoral arterial accesses in 169 patients subjected to
      vascular radiological procedures were performed (bilateral access was performed
      in 11 patients): 140 percutaneous transluminal angioplasties and 40 transarterial
      chemoembolisations. All the patients who underwent angioplasty were given 3,000
      IU of sodic heparin intravenously during the procedure and later a prolonged
      antiaggregant therapy was undertaken (ticlopidine 500 mg/day and aspirin 150
      mg/day). The sheaths were removed at the end of the surgical manoeuvre and two
      cartridges of collagen were positioned on the external surface of the artery. The
      mean values of platelets and partial thromboplastin time were 42,000/ml and 170
      s, respectively, in cirrhotic patients against 250,000/ml and 200 s in patients
      with peripheral arteriopathy. The next day a colour Doppler examination was
      performed at the puncture site. RESULTS: The technique proved successful in 89.4%
      of cases (161/180). In 19/180 vascular accesses placement of the haemostatic
      cartridges was not possible owing to the inability to compress the common femoral
      artery proximal to the release site (4/19), owing to a pre-existing haematoma
      (5/19) and owing to the limited presence of subcutaneous tissue (10/19). The mean
      time required for the placement of Vasoseal ES was 4 min. The mean time-to
      haemostasis was 6 min. The mean time-to-mobilisation was 4 hr. Only in two
      patients was there an onset of a pseudoaneurysm of the right common femoral
      artery; the lesions were treated with ultrasonography -guided compression. In
      addition, 16 small local haematomas were recorded. In 4 cases early re-puncture
      of the femoral artery was performed (24-48 hr following the use of the device)
      without consequences. CONCLUSIONS: Vasoseal ES is a safe collagen closure device
      characterised by a high success rate. In anticoagulated patients the device can
      reduce the time-to-mobilisation and the incidence of complications.

PMID- 15729193
TI  - Hereditary haemorrhagic telangiectasia: study of hepatic vascular alterations
      with multi-detector row helical CT and reconstruction programs.
AB  - PURPOSE: To evaluate hepatic alterations in patients affected by Hereditary
      Haemorrhagic Telangiectasia (HHT) by using multidetectorrow helical CT (MDCT) and
      new reconstruction programs. MATERIALS AND METHODS: An MDCT multiphasic study of
      the liver was performed in 105 consecutive patients: 89 considered to be affected
      by HHT and 16 with suspicion of disease alone. The scan delay was determined by
      using a test bolus of contrast material. The CT examination was performed with a
      triphasic technique (double arterial phase and portal venous phase). Multiplanar
      and angiographic reconstructions were then obtained, and the images checked for
      the presence of shunts, hepatic perfusion disorders, vascular lesions
      (telangiectases and large confluent vascular masses), indirect signs of portal
      hypertension, and anatomical vascular variants. RESULTS: Hepatic vascular
      alterations were found in 78/105 cases (67/89 patients affected by HHT and 11/16
      patients with clinical suspicion alone). Therefore HHT diagnosis was excluded in
      5 patients. 78/100 (78%) patients with HHT had intrahepatic vascular alterations:
      arterioportal shunts in 40/78 (51.2%), arteriosystemic shunts in 16/78 (20.5%),
      and both shunt types in 22/78 (28.3%). Intraparenchymal perfusion disorders were
      found in 46/78 (58.9%) patients. Telangiectases were recognised in 50/78 (64.1%)
      patients. Large confluent vascular masses (LCVMs) were identified in 20/78
      (25.6%) patients. Indirect signs of portal hypertension were found in 46/78
      (58.9%) cases. Variant hepatic arterial anatomy was present in 38/100 cases
      (38%). CONCLUSIONS: Multiphasic MDCT and the new reconstruction programs enable
      the identification and characterisation of the complex vascular alterations
      typical of HHT.

PMID- 15729195
TI  - Strategies for the diagnosis of gastro-esophageal reflux disease.
AB  - With patients referring symptoms of gastro-esophageal reflux disease (GERD), 2
      initial approaches should be considered: an empiric therapy (treat and test
      strategy) or a strategy based on instrumental investigations (test and treat). In
      most cases a well-taken history is usually sufficient to confirm the diagnosis of
      GERD and initiate treatment. However, some patients may present with ''atypical''
      symptoms, classic symptoms refractory to standard medical therapy or ''alarm''
      symptoms. In these cases, one must rely on diagnostic studies to document the
      presence of mucosal damage related or not to GERD and/or quantify the degree of
      gastro-esophageal reflux. The most relevant test to diagnose esophageal injury
      and complications of GERD is represented by upper gastrointestinal endoscopy,
      while the most diffuse procedure to quantify the degree of acid reflux is pH
      monitoring. Further studies are required to delineate the appropriate use and the
      possible impact of new techniques, such as intraluminal impedance monitoring,
      Bilitec and, wireless ambulatory pH monitoring in the management of GERD.

PMID- 15729194
TI  - Abdominal ultrasonography in inheredited diseases of carbohydrate metabolism.
AB  - PURPOSE: To determine the usefulness of abdominal sonography in inherited
      diseases of carbohydrate metabolism. MATERIALS AND METHODS: Thirty patients (age
      range, 4 months to 27 years) with glycogen storage diseases, galactosemia,
      disorders of fructose metabolism were studied with sonography. Echogenicity of
      the liver, sonographic dimensions of liver, kidneys and spleen were evaluated.
      Plasma blood parameters (ALT, AST, total cholesterol, triglycerides) were
      determined. RESULTS: Liver was enlarged in 21/22 patients (95.4%) with glycogen
      storage diseases, in both subjects with disorders of fructose metabolism, and in
      2/6 patients (33.3%) with galactosemia. Hepatic echogenicity was increased in
      20/22 patients (90.9%) with glycogen storage diseases, and in the subject with
      hereditary fructose intolerance. Patients with galactosemia did not show
      increased liver echogenicity. Both kidneys were enlarged in 8/17 patients (47.0%)
      with glycogen storage disease type I. Subjects with increased hepatic
      echogenicity exhibited higher plasma concentrations of any blood parameter than
      the others with normal echogenicity (p<0.05). CONCLUSIONS: Sonography can be
      useful in identification of inherited diseases of carbohydrate metabolism even if
      further examinations are necessary for an ultimate diagnosis.

PMID- 15729196
TI  - Gastroesophageal reflux and chronic cough.
AB  - Gastroesophageal reflux (GOR) disease is one of the 3 commonest causes of chronic
      cough. It can be difficult to diagnose as the traditionally recognised symptoms
      of GOR, such as heartburn and acid regurgitation, are often absent. More subtle
      indicators of a link between the cough and the oesophagus should therefore be
      sought. These include cough which occurs in relation to eating or phonation,
      cough which settles at night and does not tend to wake the patient from sleep and
      symptoms suggestive of laryngopharyngeal reflux. Investigations such as
      oesophageal manometry and 24 hour pH monitoring can be useful in characterising
      any underlying oesophageal abnormality, but may underestimate the problem since
      non-acid reflux can precipitate cough. Empirical trials of treatment are
      therefore often employed, but should be continued for at least 2 months, as
      symptoms can be slow to improve due to plasticity of the cough reflex.
      Pharmacologic treatment options include proton pump inhibitors, H2 receptor
      antagonists, pro-motility agents and liquid alginate preparations. Surgical
      fundoplication can also be effective when performed in appropriately selected
      individuals.

PMID- 15729197
TI  - Pathophysiology, diagnosis and treatment of non-erosive reflux disease (NERD).
AB  - Up to 70% of patients with typical symptoms of gastroesophageal reflux disease
      (GERD) have neither definite endoscopic oesophageal breaks nor Barrett's
      oesophagus at upper endoscopy. These patients suffer from non-erosive reflux
      disease (NERD), also termed endoscopy-negative reflux disease or symptomatic
      GERD. NERD patients appear as a heterogeneous population with multiple and
      substantially different mechanisms implicated in the genesis of symptoms. In
      fact, patients with NERD may be divided into 3 groups on the basis of 24-hour pH
      monitoring: 1) patients with an abnormal acid exposure time (AET); 2) patients
      who demonstrate a normal AET, but in whom symptoms and reflux events are
      significantly correlated (hypersensitive oesophagus) and 3) patients with typical
      reflux symptoms but in whom all parameters of the pH study are normal. There is
      no gold standard for the diagnosis of NERD but a well-taken history can be,
      usually, sufficient to confirm the diagnosis and begin therapy. Thus, the more
      sensitive tool for the diagnosis of NERD is proton pump-inhibitor (PPI) test. The
      aims of NERD treatment are: symptoms relieve, restore quality of life and
      maintain clinical remission. Proton pump-inhibitors (PPIs) in full doses
      represent the treatment of choice of NERD patients, even if overall, clinical
      trials showed a lower efficacy in symptoms control when compared to patients with
      erosive oesophagitis. Patients with NERD often need long-term therapy for
      symptoms control. ''On demand'' PPI therapy has been considered as the most cost
      effective strategy for the long-term treatment of NERD. In conclusion, many data
      indicate that NERD is a disorder in its own right that shares symptoms with other
      GERD groups. However further studies are needed to better define the natural
      history and improve the treatment of this disorder.

PMID- 15729198
TI  - The pharmacological management of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal
      disorders, and the pharmacological management of GERD is a topic of intense
      interest given the sizeable yearly expenditure for antireflux therapies. GERD is
      primarily a motor disorder of the esophagus, yet pharmacological approaches
      directed at altering esophageal motility have been only partially effective.
      Antisecretory therapy is the mainstay of treatment for GERD. Both H2 receptor
      antagonists (H2RA) and proton pump inhibitors (PPIs) are effective in the
      treatment of GERD, but PPI therapy is clearly superior in the treatment of severe
      disease and in the healing of erosive esophagitis. A treatment schema for GERD
      based on presenting symptoms is outlined, promoting a stepwise approach to the
      appropriate use of antisecretory therapy.

PMID- 15729199
TI  - Endoscopic therapy for gastroesophageal reflux disease: a systematic review.
AB  - Endoscopic therapy has emerged as an alternative for patients with symptomatic
      gastroesophageal reflux disease (GERD) who are seeking a non-pharmacologic, non
      surgical intervention. To date, there are 3 basic categories of these endoscopic
      options: radiofrequency ablation, endoscopic suturing and endoscopic injection.
      Although the pivotal clinical studies to date have consistently demonstrated
      efficacy for defined endpoints of symptom control, GERD health related quality of
      life and discontinuance of acid secretory medications, depending on the therapy,
      there has been less consistent improvement in objective parameters of pH control
      and lower esophageal sphincter pressure. Although the data for these procedures
      has been favorable, extrapolation to justify a more widespread clinical use has
      been limited by the relative lack of controlled sham studies-although these are
      currently underway for all of the available therapies. Appropriate patient
      selection for endoscopic GERD therapy is critical and at present these therapies
      have the best clinical outcome data in patients who are responsive to therapy
      with a proton pump inhibitor. The risk/benefit profile, long term durability and
      cost effectiveness should be considered in all patients being considered when
      evaluating each of the endoscopic therapies for GERD.

PMID- 15729200
TI  - Computer-assisted robotic antireflux surgery.
AB  - Robotic surgical systems are relatively new technical devices designed to address
      several of the limitations inherent to standard laparoscopy. Since the 1(st)
      report of a computer-assisted fundoplication in 1997, numerous authors have
      reported their experiences with these devices in antireflux surgery. While there
      are several advantages to robotic when compared to standard laparoscopic
      antireflux surgery, there are also some distinct drawbacks. Robotic surgical
      systems allow the surgeon to perform more complex maneuvers with increased
      precision and accuracy, and without tremor. The image is high-definition and the
      surgeon operates in a more ergonomic position. These systems are also costly to
      purchase and maintain, they are large and may limit access to the patient during
      surgery, they provide a narrower field of view of the operative site, and they
      provide the surgeon with essentially no tactile feedback. Clinical outcomes of
      robotic fundoplication seem to be very similar to those of standard laparoscopic
      fundoplication, although the operating times in many series are increased when
      using the robot. The role of computer-assisted fundoplication in general
      practice, at least at the current level of robotic technology, remains to be
      defined.

PMID- 15729201
TI  - Gastroesophageal reflux disease. Heart-burn from a psychological view.
AB  - Although gastroesophageal reflux disease (GERD) can be traced back to disorders
      of the gastroesophageal junction, stress and other relevant psychological factors
      can play an important role in the process of GERD. It would seem that, primarily,
      altered symptom perception based on threshold reduction exists in some patients.
      In an effort to describe the sensitisation for reflux symptoms, both central and
      peripheral factors can be discussed. The following is conceivable: that well
      defined personality factors moderate the effect of stress on the gastroesophageal
      junction, just as they can influence the perception and assessment of symptoms.
      Additionally, psychiatric disorders as comorbidities can also accompany GERD. For
      this reason, it is necessary to consider if an extension of hitherto
      psychological interventions could be helpful in patients with a subjective link
      between reflux and stress on an emotional personality related level, or in
      patients with attendant psychiatric disorders. This broadening relates both to
      the conservative use of antireflux medication and to surgical therapy, since a
      postoperative shift in symptoms can occur. The effectiveness of psychological
      interventions in several gastrointestinal patient groups could already be shown
      in the past, whereas evidence for their effectiveness in patients suffering with
      GERD is partly still outstanding and should be investigated in the future
      especially as several individual promising starts have been made.

PMID- 15729202
TI  - Gene expression and prognostic significance in ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological
      malignancies in the United States. Most patients with EOC will respond to
      surgical debulking followed by platinum and paclitaxel based chemotherapy.
      Unfortunately, the relapse rate within 2 years is more than 70%. The molecular
      events leading to the development of EOC and the molecular factors that may
      predict response to treatment are not well established. Such knowledge would not
      only improve the understanding of the biology of EOC, but may help in the
      identification of new tumor markers and the design of molecular therapies for
      EOC. A literature review was conducted using MEDLINE to delineate studies that
      investigated gene expression in ovarian cancer correlated with outcome. A review
      is presented of the expression and role of the BRCA1 and 2 genes, p53,
      amplification of Her2/neu, PIK3CA, AKT2, K-ras, c-myc, BRCA1, p53, p16, and p27
      in ovarian cancer. Additionally, a review of the use of microarray technology is
      presented and its use in determining expression patterns in ovarian cancer. The
      accumulation of data derived from new technologies, as well as that obtained from
      well-established methods, has provided new insights into gene expression profiles
      in EOC. The utilization of novel technologies that allow high throughput analysis
      of thousands of genes may lead to the development of new biomarkers or novel
      therapies that are urgently needed in this deadly disease.

PMID- 15729203
TI  - From gene therapy to virotherapy for ovarian cancer.
AB  - Ovarian cancer has the highest mortality of all cancers of the female
      reproductive system. Although progress in conventional therapies (surgery,
      chemotherapy and irradiation) has been achieved, the 5-year survival rate for
      patients with advanced stage ovarian cancer is still low. On this basis it is
      clear that there is a need for novel therapeutic paradigms. Targeted approaches
      are based on the increasing knowledge of the molecular basics of ovarian cancer.
      In this regard, gene therapy is a novel targeted approach for the treatment of
      ovarian cancer. However, current gene therapy delivery systems (viral and non
      viral vectors) have to address the issues of inefficient transduction of target
      ovarian cancer cells and/or ectopic non-target delivery with attendant toxicity.
      Of note, the limited tumor transduction associated with current gene therapy
      interventions is due, in large part, to the fact that the employed vectors have
      been replication-incompetent. In this regard, human clinical trials have shown
      that the approach of replication-incompetent vectors has yet to succeed in
      ovarian cancer patients. In contrast, replication-competent viruses offer a
      method to achieve efficient tumor cell oncolysis (virotherapy) in ovarian cancer.
      Thus, in this very promising approach of virotherapy the replicating virus itself
      is the anti-cancer agent. This review discusses the concepts of gene therapy and
      virotherapy as novel targeted therapeutic approaches for the treatment of ovarian
      cancer.

PMID- 15729204
TI  - Current approaches in ovarian cancer vaccines.
AB  - Much of the current approaches in the treatment of advanced ovarian cancer are
      directed towards prolongation of duration between primary treatment and
      remission. Immunotherapy is regarded as one attractive option for consolidation
      of initial therapeutic responses. In fact, immune reactivity against ovarian
      carcinoma can be induced by various immunotherapeutical approaches including
      antibodies, peptides or dendritic cell vaccines. This review provides an overview
      of recent clinical trials using various concepts of immunotherapy for the
      treatment of ovarian cancer. Possible reasons for limited clinical success as
      well as further progress to improve efficacy of current immune intervention
      strategies, e.g. by vaccines targeting a broader range of tumor-derived antigenic
      structures or activating diverse host immune functions, will be discussed.

PMID- 15729205
TI  - Intra-peritoneal administration of genetic therapies: promises and pitfalls.
AB  - Rapid advances in our understanding of the molecular basis of cancer development
      and progression over the past 3 decades have led to the design of new potential
      cancer therapies based on the expression of introduced genes into a tumor or its
      host. In an attempt to overcome the limitations of direct intratumoral
      administration of genetic therapies in patients with advanced malignant disease,
      loco-regional routes of delivery have been explored including the intraperitoneal
      route. This review highlights the potential of replication-competent oncolytic
      viruses, virus-mediated gene replacement, and gene-directed enzyme-prodrug
      strategies, as novel cancer therapies. The potential of exploiting the
      selectivity of the telomerase gene within cancer cells to develop gene therapy
      strategies is discussed and the promises and pitfalls in translating these novel
      therapeutics from the laboratory to the clinic are reviewed.

PMID- 15729206
TI  - Chemotherapy for ovarian cancer: an evidence-based approach.
AB  - Although cytoreductive surgery is the most influential factor in treatment for
      ovarian cancer, chemotherapy is needed for almost all patients diagnosed with
      this disease. The mainstay of chemotherapy is platinum. Different platinum
      compounds are used for different histologies, and different combinations are used
      for different histologies also. We will present the data so that each reader can
      understand the knowledge behind chemotherapy decisions.

PMID- 15729207
TI  - Surgical management of epithelial ovarian cancer: a review of the literature.
AB  - Epithelial ovarian cancer affects over 190,000 women worldwide. Over the past 40
      years the median survival rate for women affected with this disease has increased
      from 12 months to 38 months. While advances in chemotherapy have enhanced our
      armamentarium, optimal cytoreductive surgery by well trained specialists offers
      the best opportunity for a long disease free interval.

PMID- 15729208
TI  - Some current controversies in heart failure (2004-2005).
AB  - The disparity between what doctor's believe and the medical facts can be
      frightening at times. This reflects centuries of training on how to manage
      patients in the absence of evidence to guide practice. Increasingly disease is
      becoming susceptible to treatment, requiring a change in the professional
      approach from the educated, hopeful guess to the application of objective data.
      Arrogance and certainty, born of ignorance and clutching in desperation at
      imaginary straws probably still have a place in medicine when conventional
      treatment has failed, but should play a diminishing role within the medical
      profession. Epidemiological association is no longer sufficient evidence to
      conclude that an intervention is effective; with few exceptions, randomised
      controlled trials are required. A more successful and objective era of medical
      practice has arrived. Consequently, a greater degree of scepticism about claims
      of benefit is also appropriate, which should apply equally to treatments new and
      old. Of course, no 2 patients are alike, and the evidence-base remains a guide
      map on how patients should be treated, rather than a set of rigid rules.
      Guidelines are guidelines and not infallible, inviolable decrees. In this
      article, some of the current controversies in the management of heart failure are
      discussed, ranging from diagnosis, diastolic heart failure, and the role of
      natriuretic peptides, to the lack of evidence for a clinically-relevant benefit
      (and therefore possible harm) from aspirin, statins, implantable defibrillators
      or revascularisation.

PMID- 15729209
TI  - Clinical applications of B-type natriuretic peptide levels in the care of
      cardiovascular patients.
AB  - B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as
      prepro BNP and then enzymatically cleaved to the N-terminal-proBNP and BNP upon
      ventricular myocyte stretch. Blood measurements of BNP have been used to identify
      patients with heart failure (HF). The BNP assay is currently used in diagnosis,
      prognosis, screening, and response to treatment for patients with HF. In general,
      a BNP level below 100 pg/mL excludes acutely decompensated HF and levels > 500
      pg/ml indicate decompensation. There are supportive data for using BNP to guide
      both inpatient and outpatient HF diagnosis and treatment. When BNP is elevated in
      acute coronary syndromes, pulmonary embolism, and sepsis, it implies that
      subclinical left ventricular dysfunction is present and a higher mortality rate
      can be expected. Elevated BNP levels before cardiac surgery are associated with
      higher rates of atrial fibrillation and death. After bypass surgery, as left
      ventricular function improves, the BNP level can be expected to fall. Lastly, in
      patients with aortic stenosis, aortic regurgitation, and mitral regurgitation,
      BNP elevates and is associated or may precede the development of symptoms and
      possibly can serve as a trigger for additional evaluation or intervention.

PMID- 15729210
TI  - Heart failure in diabetes mellitus: causal and treatment considerations.
AB  - The metabolic abnormalities associated with diabetes mellitus result in
      macrovascular and microvascular complications in multiple organ systems; it is
      the cardiovascular impact that accounts for the greatest morbidity and mortality
      associated with this disease. Heart failure, both with reduced and preserved
      systolic function, is a major complication, arising from the frequent
      associations with coronary atherosclerosis, hypertension, and a specific heart
      muscle dysfunction (cardiomyopathy) that occurs independently of coronary artery
      disease. Hyperglycemia, insulin resistance, and hypertension, together with
      activation of both circulating and tissue renin-angiotensin-aldosterone systems,
      contribute to structural fibrosis and autonomic neuropathy. Thus it becomes
      imperative to identify cardiac abnormalities early in the course of both type 1
      and type 2 diabetes in order to allow early and aggressive intervention to
      control glucose and blood pressure and to normalize blood lipid profiles.
      Patients with diabetes should be treated to secondary prevention targets,
      including blood pressure less than 130/80 mm Hg and LDL less than 100 mg/dL.
      Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta
      blockers, certain calcium channel blockers, statins, and aspirin have all been
      demonstrated to significantly reduce cardiovascular morbidity and mortality in
      patients with diabetes.

PMID- 15729211
TI  - Modern nuclear cardiac imaging in diagnosis and clinical management of patients
      with left ventricular dysfunction.
AB  - Congestive heart failure (CHF) has become a large social burden in modern Western
      society, with very high morbidity and mortality and extremely large financial
      costs. The largest cause of CHF is coronary heart disease, with ventricular
      dysfunction that may or may not be reversible by revascularization. Thus,
      evaluation of the viable myocardial tissue in patients with ischemic left
      ventricular (LV) dysfunction has important clinical and therapeutic implications.
      Furthermore, since patients with ventricular dysfunction are at higher operative
      risk, cardiologists and cardiac surgeons are commonly faced with issues regarding
      the balance between the potential risk vs benefit of revascularization
      procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and
      positron emission tomography (PET)] provide objective information that augments
      standard clinical and angiographic assessments of patients with ventricular
      dysfunction with respect to diagnosis (etiology), prognosis, and potential
      benefit from intervention. Development of the technology and methodology of gated
      MPS, now the routine method for MPS, allows assessment of the extent and severity
      of inducible ischemia as well as hypoperfused but viable myocardium, and also
      provides measurements of LV ejection fraction, regional wall motion, LV volume
      measurements, diastolic function and LV geometry. With PET, myocardial metabolism
      and blood flow reserve can be added to the measurements provided by nuclear
      cardiology procedures. This paper provides insight into the current evidence
      regarding settings in which nuclear cardiac imaging procedures are helpful in
      assessment of patients in the setting of coronary artery disease with severe LV
      dysfunction. A risk-benefit approach to MPS results is proposed, with principal
      focus on identifying patients at risk for major cardiac events who may benefit
      from myocardial revascularization.

PMID- 15729212
TI  - Heart failure therapy and sudden cardiac death prevention.
AB  - Primary prophylaxis of sudden cardiac death by implantable defibrillators is an
      accepted therapeutic strategy because sudden cardiac death is reduced by their
      use. However, many patients at risk of sudden cardiac death due to left
      ventricular systolic dysfunction also suffer heart failure symptoms. There is
      increasing evidence that the morbidity of heart failure can be alleviated by
      device therapy in which ventricular dysynchrony is improved by biventricular
      pacing. Both therapies in the same device can reduce both morbidity and
      mortality. Device therapy is an important new aspect in the field of heart
      failure management.

PMID- 15729214
TI  - Exercise and heart failure.
AB  - This report will review the abnormalities of the peripheral circulation and
      skeletal muscle which are part of the heart failure syndrome and can limit
      exercise tolerance; introduce trials that have shown benefits of exercise
      training in a variety of heart failure patients; suggest strategies for
      recommending activity training in patients with heart failure. Finally, this
      report will identify areas where data are missing and where trials are currently
      being undertaken.

PMID- 15729215
TI  - The clinical and electrophysiological implications of asymptomatic atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is the commonest arrhythmia encountered in clinical
      practice and is frequently associated with significant symptoms. Asymptomatic AF
      may also increase the risks of heart failure, thromboembolism and cardiomyopathy
      but its prevalence is significantly underestimated by routine surveillance
      methods. The development of long-term external monitors and implantable devices
      has offered a new insight into the true prevalence of asymptomatic AF. Similar
      management strategies should be applied to both symptomatic and asymptomatic
      patient groups and anticoagulation should be continued indefinitely in those with
      a history of AF and risk factors for thromboembolism. Enhanced detection of
      clinically silent AF could improve outcomes but the resource implications will be
      significant.

PMID- 15729213
TI  - Myocardial repair with autologous skeletal myoblasts: a review of the clinical
      studies and problems.
AB  - Stem cell therapy for myocardial repair after myocardial infarction is a new and
      promising treatment modality. Currently, bone marrow derived stem cells are used
      in clinical studies to evaluate its beneficial effect on repair of
      infarcted/hibernating myocardium in the subacute phase after myocardial
      infarction. Whereas skeletal myoblasts are nowadays under investigation in the
      setting of scar repair in chronic congestive heart failure patients. The
      mechanism of bone marrow derived stem cells is probably mainly related to
      induction and stimulation of angiogenesis, whereas skeletal myoblasts are more
      likely to contribute to recovery of left ventricular function by the direct
      engraftment of contractile cells and hypothetically indirect by stimulation of
      native and circulation stem cells to home into the scarred tissue. This review
      will focus on the use of skeletal myoblasts in all clinical studies presented
      sofar and will discuss several issues like: different transplantation methods,
      potential mechanism of effect, potential risks like arrhythmia and future
      concepts. As the target population of skeletal myoblast transplantation is
      chronic post myocardial infarction heart failure patients, ventricular
      arrhythmias are very likely to occur. This review will specially address the
      presence of ventricular arrhythmias observed in some clinical studies and the pre
      clinical data on the electrophysiology of skeletal myotubes and its relationship
      to the surrounding myocardium.

PMID- 15729216
TI  - Legionnaires disease associated with potable water in a hotel--Ocean City,
      Maryland, October 2003-February 2004.
AB  - During October 2003-February 2004, eight cases (seven confirmed cases and one
      possible) of Legionnaires disease (LD) were identified among guests at a hotel in
      Ocean City, Maryland. This report summarizes the subsequent investigation
      conducted by the Worcester County Health Department (WCHD), Maryland Department
      of Health and Mental Hygiene (DHMH), and CDC, which implicated the potable hot
      water system of the hotel as the most likely source of infection. The detection
      of this outbreak underscores the importance of enhanced, state-based surveillance
      for timely detection of travel-associated LD and implementation of control
      measures.

PMID- 15729217
TI  - Fatal bacterial infections associated with platelet transfusions--United States,
      2004.
AB  - Each year, approximately 9 million platelet-unit concentrates are transfused in
      the United States; an estimated one in 1,000-3,000 platelet units are
      contaminated with bacteria, resulting in transfusion-associated sepsis in many
      recipients. To reduce this risk, AABB (formerly the American Association of Blood
      Banks) adopted a new standard on March 1, 2004, that requires member blood banks
      and transfusion services to implement measures to detect and limit bacterial
      contamination in all platelet components. This report summarizes two fatal cases
      of transfusion-associated sepsis in platelet recipients in 2004 and describes
      results of a 2004 survey of infectious-disease consultants regarding their
      knowledge of transfusion-associated bacterial infections and the new AABB
      standard. Health-care providers should be aware of the new standard and the need
      for bacterial testing of platelets to improve transfusion safety. However, health
      care providers also should be able to diagnose transfusion-associated infections,
      because even when testing complies with the new standard, false negatives can
      occur and fatal bacterial sepsis can result.

PMID- 15729218
TI  - Tularemia transmitted by insect bites--Wyoming, 2001-2003.
AB  - Tularemia is a zoonotic disease caused by Francisella tularensis, a fastidious,
      gram-negative coccobacillus that infects vertebrates, especially rabbits and
      rodents. In humans, tularemia is classified into six major syndromes:
      ulceroglandular (the most common form), glandular, typhoidal, oculoglandular,
      oropharyngeal, and pneumonic. The case-fatality rate among humans can reach 30%
      60% in untreated typhoidal cases. Although bites from ticks and handling infected
      animals are considered the most common modes of tularemia transmission in the
      United States, the disease also is spread through ingestion of contaminated food
      or water, inhalation, and insect bites. During 2001-2003, Wyoming experienced an
      increase in reported human cases of tularemia. This report describes the
      subsequent investigation by the Wyoming Department of Health (WDH), which
      indicated that 1) insect bites (particularly from deerflies and other horseflies)
      were the most commonly reported likely mode of transmission, and 2) the increase
      in cases was geographically and temporally associated with an outbreak of
      tularemia among rabbits in southwestern Wyoming. To obtain a timely diagnosis and
      provide information on appropriate preventive measures, health-care providers and
      public health officials should have knowledge of the local epidemiology of
      tularemia, particularly regarding modes of transmission and resultant clinical
      syndromes.

PMID- 15729219
TI  - Hypothermia-related deaths--United States, 2003-2004.
AB  - Hypothermia, a reduction in the body's core temperature to <95.0 degrees F (<35.0
      degrees C), is a preventable medical emergency usually caused by prolonged
      exposure to cold temperatures without adequate protective clothing. Warning signs
      and symptoms of hypothermia include lethargy, weakness and loss of coordination,
      confusion, uncontrollable shivering, and reduced respiratory or heart rate.
      Common risk factors are advanced age, substance abuse, altered mental status, and
      increased contact with substances that promote heat loss, such as water. This
      report describes three hypothermia-related deaths that occurred in the United
      States during 2003-2004, summarizes hypothermia-related mortality during 1979
      2002, describes risk factors for and symptoms of hypothermia, and reviews
      measures to prevent hypothermia-related injury and death. Public health
      strategies tailored to persons at increased risk for exposure to excessive cold
      might help reduce hypothermia-related morbidity and mortality.

PMID- 15729220
TI  - Progress toward elimination of measles and prevention of congenital rubella
      infection--European region, 1990-2004.
AB  - The European Region (EUR) of the World Health Organization (WHO) comprises 52
      member countries, with an estimated population of 876 million. In 1998, the
      Regional Committee for EUR resolved to interrupt indigenous measles transmission
      by 2007 and reduce the incidence of congenital rubella syndrome (CRS) in all
      countries to <1 per 100,000 live births by 2010. In 2002, progress toward these
      measles and rubella targets was further encouraged with development of the
      Strategic Plan for Measles and Congenital Rubella Infection in the WHO European
      Region, which outlines an integrated approach to achieving both disease targets
      by 2010 by implementing six key strategies. This report presents data on measles,
      rubella, and CRS control in EUR during 1990-2004 and summarizes progress halfway
      through the implementation of the strategic plan.

PMID- 15729224
TI  - ASGE guideline: the management of low-molecular-weight heparin and nonaspirin
      antiplatelet agents for endoscopic procedures.
AB  - This is one of a series of statements discussing the utilization of GI endoscopy
      in common clinical situations. The Standards of Practice Committee of the
      American Society for Gastrointestinal Endoscopy prepared this text. In preparing
      this guideline, a MEDLINE literature search was performed, and additional
      references were obtained from the bibliographies of the identified articles and
      from recommendations of expert consultants. When little or no data exist from
      well-designed prospective trials, emphasis is given to results from large series
      and reports from recognized experts. Guidelines for appropriate use of endoscopy
      are based on a critical review of the available data and expert consensus.
      Further controlled clinical studies are needed to clarify aspects of this
      statement, and revision may be necessary as new data appear. Clinical
      consideration may justify a course of action at variance to these
      recommendations.

PMID- 15729225
TI  - Premedication with orally administered midazolam in adults undergoing diagnostic
      upper endoscopy: a double-blind placebo-controlled randomized trial.
AB  - BACKGROUND: A double-blind placebo-controlled randomized trial was conducted to
      investigate the safety and the efficacy of orally administered midazolam as
      premedication for patients undergoing elective EGD. METHODS: A total of 130
      patients were randomized to receive either 7.5 mg of midazolam orally (n = 65) or
      a placebo (n = 65) as premedication. Outcomes measures included the anxiety score
      (visual analog scale) during EGD, overall tolerance, extent of amnesia, overall
      satisfaction, patient willingness to repeat the procedure, recovery time, and
      hemodynamic changes after medication. RESULTS: The median (interquartile range)
      anxiety score during the procedure in the midazolam group was significantly lower
      than that in the control group (2.0 [0-4.9] vs. 3.8 [2.1-7.95], p < 0.001). A
      significantly greater number of patients in the midazolam group graded overall
      tolerance as "excellent or good" (70.8% vs. 49.2%, p = 0.012) and reported a
      partial to complete amnesia response (52.3% vs. 32.3%, p = 0.02) when compared
      with the control group. Patients in the midazolam group were more willing to
      repeat the procedure if necessary (89.2% vs. 69.2%, p = 0.005). The median
      (interquartile range) recovery time was significantly longer in the midazolam
      group than in the control group (5 [5-15] minutes vs. 5 [5-10] minutes, p =
      0.014). There were no statistically significant differences in satisfaction score
      and hemodynamic changes between groups. CONCLUSIONS: Premedication by oral
      administration of midazolam is a safe and an effective method of sedation that
      significantly reduces anxiety and improves overall tolerance for patients
      undergoing EGD.

PMID- 15729226
TI  - From oral midazolam to propofol: a perspective.

PMID- 15729228
TI  - Endoscopic simulation: where we have been and where we are going.

PMID- 15729227
TI  - Training with the compactEASIE biologic endoscopy simulator significantly
      improves hemostatic technical skill of gastroenterology fellows: a randomized
      controlled comparison with clinical endoscopy training alone.
AB  - BACKGROUND: The Erlangen Active Simulator for Interventional Endoscopy (EASIE)
      was introduced in 1997 for interventional endoscopy training. compactEASIE
      developed in 1998 is a modified, light-weight version of the original model.
      Objective evidence of the benefits of training with these models is limited. A
      randomized controlled study, therefore, was conducted to compare the effects of
      intensive 7-month, hands-on training in hemostatic techniques by using the
      compactEASIE model (in addition to clinical endoscopic training) vs. pure
      clinical training in endoscopic hemostatic methods. METHODS: Thirty-seven fellows
      in gastroenterology in New York City area training programs were enrolled.
      Baseline skills were assessed on the simulator for the following techniques:
      manual skills, injection and electrocoagulation, hemoclip application, and
      variceal ligation. Twenty-eight fellows were then randomized into two comparable
      groups. Those randomized to Group A received purely clinical training in
      endoscopic hemostatic techniques at their hospitals. Those in Group B, in
      addition, were trained by experienced tutors in 3 full-day hemostasis workshops
      over 7 months. Both groups underwent a final evaluation on the compactEASIE
      simulator conducted by their tutors and additional evaluators who were blinded to
      the method of training. Initial and final evaluation scores were compared for
      each group and between groups. Outcomes of actual clinical hemostatic procedures
      performed during the study period also were analyzed. RESULTS: Ten of 14 fellows
      randomized to Group A (standard training) and 13 of 14 in Group B (intensive
      training) returned for the final evaluation. For Group B, scores for all
      techniques were significantly improved. In Group A, a significant improvement was
      noted for variceal ligation alone. CONCLUSIONS: compactEASIE simulator training
      (3 sessions over 7 months), together with clinical endoscopic training resulted
      in objective improvement in the performance by fellows of all 4 endoscopic
      hemostatic techniques, whereas significant improvement was noted for variceal
      ligation alone for fellows who had standard clinical training. In clinical
      practice, fellows who had intensive simulator/clinical training had a
      significantly higher success rate and a nonsignificant reduction in the frequency
      of occurrence of complications.

PMID- 15729229
TI  - Local recurrence of squamous-cell carcinoma of the esophagus after EMR.
AB  - BACKGROUND: Multicentric squamous dysplasia is frequent in the esophagus and can
      be visualized by chromoendoscopy (Lugol's solution) as multiple Lugol-voiding
      lesions (LVLs). Although EMR commonly is used to treat superficial esophageal
      cancer, new lesions can arise and incomplete resection can result in residual
      disease. Little is known about the risk factors for local recurrence or the
      appropriate treatment for recurrent lesions. METHODS: A total of 116 consecutive
      patients with a total of 165 esophageal squamous-cell carcinomas were studied
      retrospectively. Follow-up examination by means of chromoendoscopy (Lugol's
      solution) and biopsies was performed every 3 months during the first year after
      EMR and every 6 months thereafter. Lesions were defined as a local recurrence
      when cancer was detected at the site of the EMR scar. Risk factors associated
      with local recurrence were investigated by using logistic analysis. RESULTS: At a
      median follow-up of 35 months (range 12-110 months), local recurrence was
      detected for 33 (20%) of 165 lesions. Of the patient-related factors,
      multivariate logistic analysis showed that multiple LVLs (OR 3.1: 95% CI[1.1,
      8.5]; p = 0.03) was an independent risk factor for local recurrence after EMR.
      The cumulative local recurrence rates at 3 years in patients with multiple LVLs
      and those without multiple LVLs were 39% and 14% (p < 0.01), respectively. All of
      the recurrent lesions except two could be removed by EMR, which was not
      associated with any serious complication. The remaining two patients had
      chemoradiotherapy. Overall cause-specific survival at 3 years was 100%.
      CONCLUSIONS: Patients with multiple LVLs are at risk of local recurrence after
      EMR. Although careful long-term endoscopic follow-up is needed for such patients,
      EMR is potentially curative for recurrent lesions.

PMID- 15729230
TI  - The frequency of Barrett's esophagus in high-risk patients with chronic GERD.
AB  - BACKGROUND: The reported frequency of Barrett's esophagus (BE) in patients with
      reflux symptoms varies from 5% to 15%. The exact frequency of long-segment BE
      (LSBE) (>3 cm) and short-segment BE (SSBE) (<3 cm) in patients with chronic
      symptoms of GERD is uncertain. The aim of this study was to determine the
      frequency of LSBE and SSBE in consecutive patients presenting for a first
      endoscopic evaluation with GERD as the indication. METHODS: Consecutive patients
      presenting to the endoscopy unit of a Veterans Affairs Medical Center for a first
      upper endoscopy with the indication of GERD were prospectively evaluated.
      Demographic information (gender, race, age), data on tobacco use and family
      history of esophageal disease, and body mass index (BMI) were recorded for all
      patients. Before endoscopy, all patients completed a validated GERD
      questionnaire. The diagnosis of BE was based on the presence of columnar
      appearing mucosa in the distal esophagus, with confirmation by demonstration of
      intestinal metaplasia in biopsy specimens. All patients with erosive esophagitis
      on the initial endoscopy underwent a second endoscopy to document healing and to
      rule-out underlying BE. Patients with a history of BE, alarm symptoms (dysphagia,
      weight loss, anemia, evidence of GI bleeding), or prior endoscopy were excluded.
      RESULTS: A total of 378 consecutive patients with GERD (94% men, 86% white;
      median age 56 years, range 27-93 years) were evaluated. A diagnosis of BE was
      made in 50 patients (13.2%). The median length of Barrett's esophagus (BE) was
      1.0 cm (range 0.5-15.0 cm). Of the patients with BE, 64% had short-segment BE
      (SSBE) (overall SSBE frequency 8.5%). The overall frequency of long-segment BE
      (LSBE) was 4.8%. A hiatal hernia was detected in 62% of the patients with BE. Of
      the 50 patients with BE (median age 62 years, range 29-81 years), 47 (94%) were
      men and 98% were white. Eighteen patients (36%) were using tobacco at the time of
      endoscopy; 23 (46%) were former users. The median body mass index (BMI) of
      patients with BE was 27.3 (overweight). There were no significant differences
      between patients with LSBE and SSBE with respect to age, gender, ethnicity, BMI,
      and GERD symptom duration. CONCLUSIONS: The frequency of BE in a high-risk
      patient group (chronic GERD, majority white men, age > 50 years) who sought
      medical attention is 13.2%, with the majority (64%) having SSBE. These data
      suggest that the frequency of BE in patients with GERD has not changed. The true
      prevalence of BE in the general population, including those who do not seek care,
      is undoubtedly lower, currently and historically. The majority of patients with
      BE are overweight and have a hiatal hernia. Demographic data for patients with
      LSBE and SSBE are similar, indicating that these are a continuum of the same
      process.

PMID- 15729231
TI  - Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation
      for ablation of Barrett's esophagus.
AB  - BACKGROUND: Endoscopic ablation of Barrett's esophagus has been described in
      which various thermocoagulation modalities are used in combination with a high
      dose of a proton pump inhibitor. No randomized comparison of ablation strategies
      has been published. METHODS: Referred patients were screened to identify those
      with Barrett's esophagus 2 to 7 cm in length, without high-grade dysplasia or
      cancer. Included patients received pantoprazole (40 mg twice a day), followed by
      randomization to treatment with argon plasma coagulation (APC) or multipolar
      electrocoagulation (MPEC). The primary outcome measure was the number of
      treatment sessions required for endoscopic ablation. RESULTS: Of 235 patients
      screened, 52 were randomized. The mean length of Barrett's esophagus was 3.1 cm
      in the MPEC group vs. 4.0 cm in the APC group (p = 0.03). Otherwise, the
      treatment groups were similar with regard to baseline characteristics. The mean
      number of treatment sessions required for endoscopic ablation was 2.9 for MPEC
      vs. 3.8 for APC (p = 0.04) in an intention-to-treat analysis (p = 0.249, after
      adjustment for the difference in length of Barrett's esophagus). The proportion
      of patients in which ablation was endoscopically achieved proximal to the
      gastroesophageal junction was 88% for the MPEC group vs. 81% for the APC group (p
      = 0.68) and histologically achieved in 81% for MPEC vs. 65% for APC (p = 0.21).
      The mean time required for the first treatment session was 6 minutes with MPEC
      vs. 10 minutes with APC (p = 0.01) in per protocol analysis. There was no serious
      adverse event, but transient moderate to severe upper-GI symptoms occurred after
      MPEC in 8% vs. 13% after APC (p = 0.64). Conclusions Although there were no
      statistically significant differences, ablation of Barrett's esophagus with
      pantoprazole and MPEC required numerically fewer treatment sessions, and
      endoscopic and histologic ablation was achieved in a greater proportion of
      patients compared with treatment with pantoprazole and APC.

PMID- 15729232
TI  - The better burn.

PMID- 15729233
TI  - Does the "Suspected Blood Indicator" improve the detection of bleeding lesions by
      capsule endoscopy?
AB  - BACKGROUND: The "Suspected Blood Indicator" (SBI), a feature included in the
      software for interpretation of capsule endoscopy (CE), is designed to facilitate
      detection of bleeding lesions in the small bowel. This study evaluated the
      sensitivity and the specificity of the SBI in patients who underwent CE for
      obscure GI bleeding (OGIB). METHODS: CE recordings from patients with OGIB
      recruited in 7 centers were read by experts blinded to the red SBI tags. They
      classified lesions of interest as bleeding or as having a potential for bleeding
      that was high (P2), low (P1), or absent (P0). The SBI tags then were marked by a
      another investigator. Concordance was acknowledged when frames selected by the
      expert reader, and those tagged by the SBI had the same time code. RESULTS: A
      total of 156 recordings were evaluated. In 83, there was either no lesion (n =
      71) or a P0 lesion (n = 12); these CE recordings were regarded as normal. Among
      the 73 abnormal recordings, 114 P2 and 92 P1 lesions were identified. A total of
      154 red tags were analyzed. Sensitivity, specificity, and positive and negative
      predictive values of SBI were 37%, 59%, 50%, and 46%, respectively, for detection
      of the presence of a P2 or P1 lesion in front of a red tag. CONCLUSIONS: SBI
      based detection of intestinal lesions with the potential for bleeding is of
      limited clinical value in practice and does not reduce the time required for
      interpretation of CE.

PMID- 15729234
TI  - Electromagnetic interference with implantable cardiac pacemakers by video
      capsule.
AB  - BACKGROUND: Electromagnetic fields, such as those generated by cellular phones
      and metal detectors, may interfere with normal pacemaker function. However, it
      remains unclear whether the wireless capsule endoscope interacts with implanted
      pacemakers. This prospective study evaluated potential interactions between the
      M2A video capsule (Given Imaging, Yoknam, Israel) and implanted pacemakers.
      METHODS: A total of 100 consecutive patients (70 men, 30 women) with an implanted
      pacemaker (95 on bipolar mode) were studied. The testing was performed with a
      functional testing device (Test Cap) for the Given Diagnostic System that
      reproduces the effect of the video capsule by transmitting at exactly the same
      frequency. During continuous electrocardiographic monitoring and recording, 100
      tests were carried out without changing the pacemaker settings. Those with a
      positive result were retested 1 week later. RESULTS: The 100 pacemakers evaluated
      in the study population included the following: 70 dual chamber (11 DDD, 56 DDDR,
      3 VDD) and 30 ventricular inhibited (12 VVI, 18 VVIR). In 4 of the 100 patients,
      pacemaker interference (noise-mode function forcing a synchronous mode) was
      registered during the Test Cap operation. Three patients had a dual-chamber
      pacemaker, and one had a single-chamber pacemaker. The interference was
      reproducible in all cases 1 week later. None of the implanted pacemakers tested
      was affected by oversensing. CONCLUSIONS: Electromagnetic interferences with
      pacemakers from the M2A video capsule can occur, but this is without clinical
      significance. No potentially dangerous pacemaker inhibition was observed.

PMID- 15729236
TI  - Capsule endoscopy and Crohn's disease.

PMID- 15729235
TI  - Capsule endoscopy vs. push enteroscopy and enteroclysis in suspected small-bowel
      Crohn's disease.
AB  - BACKGROUND: The diagnosis of small-bowel Crohn's disease sometimes is difficult
      and may be missed by conventional imaging studies. Capsule endoscopy might
      identify small-bowel disease undetected by other investigations. METHODS:
      Patients with or without known Crohn's disease who were suspected to have small
      bowel Crohn's disease were prospectively evaluated with push enteroscopy,
      enteroclysis, and capsule endoscopy. Each examiner was blinded to results of
      other investigations. Referring doctors were required to complete questionnaires
      before and after the investigations. RESULTS: Twenty-two patients were known to
      have Crohn's disease (Group 1), and 21 were suspected to have small-bowel Crohn's
      disease (Group 2). In Group 1, capsule endoscopy detected more erosions than the
      other two investigations (p < 0.001). In Group 2, a new diagnosis of Crohn's
      disease was made in two patients, but there was no significant difference in
      yield compared with the other two investigations. Referring physicians rated the
      usefulness of capsule endoscopy as 4.4 on a scale of 5. Capsule endoscopy changed
      management for 30 patients (70%). CONCLUSIONS: Capsule endoscopy has a higher
      yield than push enteroscopy and enteroclysis in patients with known Crohn's
      disease when small-bowel mucosal disease is suspected, and this leads to a change
      in management in the majority of these patients.

PMID- 15729237
TI  - Precancerous mucosal changes in the gallbladder of patients with occult
      pancreatobiliary reflux.
AB  - BACKGROUND: Pancreatobiliary reflux can occur even if the pancreaticobiliary
      junction is normal (occult pancreatobiliary reflux), and it may be associated
      with gallbladder carcinoma. The aim of the present study was to examine
      precancerous mucosal changes in the gallbladder from patients with occult
      pancreatobiliary reflux. METHODS: The mucosa of the gallbladder from 13 patients
      who underwent cholecystectomy was examined histopathologically. These patients
      had an anatomically normal pancreatobiliary junction and a biliary amylase
      concentration greater than 10,000 IU/L. The gallbladder of patients without
      carcinoma was further examined by using immunohistochemical techniques to detect
      Ki-67, and the results were compared with those from control patients. RESULTS:
      Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the
      8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia,
      and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling
      index was significantly higher in hyperplastic and dysplastic mucosa than in
      control gallbladder mucosa (p < 0.0004). CONCLUSIONS: Occult pancreatobiliary
      reflux could be associated with precancerous mucosal changes in the gallbladder,
      such as hyperplasia and dysplasia with increased cellular proliferation, and
      could be a possible risk factor for gallbladder carcinoma.

PMID- 15729239
TI  - Postcholecystectomy bile leak: what is the optimal treatment?

PMID- 15729238
TI  - Impact of endoscopic intervention in 100 patients with suspected
      postcholecystectomy bile leak.
AB  - BACKGROUND: Bile leak is a recognized complication of cholecystectomy. Endoscopic
      intervention is widely accepted as a treatment for this complication, but the
      optimal form is not well defined. METHODS: An ERCP database was reviewed
      retrospectively to identify all cases of bile leak related to cholecystectomy.
      Patient records and endoscopy reports were reviewed, and structured telephone
      interviews were conducted to collect data. RESULTS: A total of 100 patients (61
      women, 39 men; mean age, 53 [17] years) with suspected postcholecystectomy bile
      leak were referred for ERCP. Cholecystectomy was commenced laparoscopically in 83
      patients (with an open conversion rate of 30%). The most common symptoms were
      pain (n = 62) and fever (n = 37). Cholangiography was obtained in 96 patients. A
      leak was identified in 80/96 patients, the most common site being the cystic-duct
      stump (48), followed by ducts of Luschka (15), the T-tube site (7), and other
      sites (10). Treatment included stent insertion alone (40), sphincterotomy alone
      (18), combination stent/sphincterotomy (31), none (6), and other (1). Three
      patients with major bile-duct injuries were excluded from the analysis.
      Endoscopic therapy was unsuccessful in 7 patients (6 in the sphincterotomy alone
      group; p = 0.001). Four patients underwent surgery subsequent to ERCP to control
      the leak. All 4 were in the sphincterotomy alone group ( p = 0.001). Post-ERCP
      pancreatitis developed in 4 patients (3 mild, 1 moderate). CONCLUSIONS: The
      optimal endoscopic intervention for postcholecystectomy bile leak should include
      temporary insertion of a biliary stent.

PMID- 15729240
TI  - Proposing a good research question: a simple formula for success.

PMID- 15729242
TI  - Retained endoclip.

PMID- 15729243
TI  - Posttransplantation lymphoproliferative disorder.

PMID- 15729244
TI  - Bronchogastric fistula.

PMID- 15729245
TI  - Gastric submucosal tumor removal.

PMID- 15729246
TI  - Atypical herpes simplex esophagitis.

PMID- 15729247
TI  - Giant appendicolith.

PMID- 15729248
TI  - Isolated ileocecal lymphoma.

PMID- 15729249
TI  - Mantle-cell lymphoma of colon.

PMID- 15729250
TI  - Esophageal perforation by cervical fixation device.

PMID- 15729251
TI  - The effect on porcine bile duct of a metallic stent covered with a paclitaxel
      incorporated membrane.
AB  - BACKGROUND: Biliary metallic stents are covered with a membrane to prevent tumor
      ingrowth and to prolong patency. The only function of these stents is to promote
      biliary drainage; they have no antitumor effect. METHODS: A metallic stent was
      developed that is covered with a paclitaxel-incorporated membrane. The metallic
      stents were coated with one of 3 concentrations of paclitaxel (0, 10, and 20 %
      wt/v) and polyurethane. A stent with each concentration was surgically inserted
      in the bile duct of two pigs. Four weeks after insertion, the segment of bile
      duct containing the stent was examined histologically. To determine the efficacy
      of the drug release, stents were placed in phosphate buffered saline solution for
      6 weeks, and the amount of paclitaxel released was measured by high-performance
      liquid chromatography. RESULTS: The histologic changes in the pig biliary
      epithelium were acceptable with respect to safety and included inflammatory cell
      infiltration and fibrous reactions. The changes corresponded to the amount of
      paclitaxel incorporated within the stent in contact with the bile duct.
      Epithelial denudation, mucin hypersecretion, and epithelial metaplasia were noted
      in the bile ducts that were in contact with stents containing 20 % wt/v
      paclitaxel. Transmural necrosis and perforation were not observed in any animal.
      In the in vitro experiment, the amounts of paclitaxel released over 1 week and
      over 6 weeks were similar, regardless of the concentration of paclitaxel
      incorporated in the stent. The stent with 10% (wt/v) paclitaxel in the covering
      membrane was found to be better than that with 20 % (wt/v) with respect to
      histologic changes and the effectiveness of drug release. CONCLUSIONS: A
      paclitaxel-incorporated metallic stent could serve as a basis for the development
      of a new and safe treatment modality for malignant biliary obstruction. Clinical
      trials of this stent with other adjuvant therapy are warranted.

PMID- 15729252
TI  - Randomized trial of a video headset vs. a conventional video monitor during
      colonoscopy.
AB  - BACKGROUND: Head-mounted video displays recently became available for endoscopy.
      This study compared a video headset with a conventional monitor during
      colonoscopy. METHODS: Five endoscopists were randomized to headset or to monitor
      use during colonoscopy. They completed a questionnaire that assessed image
      quality, procedure characteristics, and comfort. Medication use and length of
      procedure were recorded. RESULTS: A total of 96 colonoscopies were performed.
      Image quality and comfort were rated as poorer during headset use (p < 0.05).
      However, neck strain was significantly reduced with the headset. Medication use
      and total procedure time were similar. There was a trend toward increased time to
      cecum with the headset (9.8 vs. 8.0 minutes, p = 0.055). CONCLUSIONS: In this
      randomized study, comparing a video headset and a conventional monitor for
      colonoscopy, image quality and comfort were inferior with the headset, although
      neck strain was improved. Further improvements in technology are needed before
      headsets can be considered an acceptable alternative to the conventional video
      monitor for GI endoscopy.

PMID- 15729253
TI  - EUS-guided transhepatic cholangiography: report of 6 cases.
AB  - BACKGROUND: This report describes a novel application of EUS-guided
      cholangiography in which a transhepatic approach was used to alleviate perihilar
      and distal biliary obstructions when this could not be accomplished at ERCP.
      METHODS: EUS-guided transhepatic cholangiography was used to alleviate symptoms
      of biliary obstruction in 6 patients. In 4 cases, after transgastric puncture of
      an intrahepatic branch of the obstructed bile duct with a 19- or a 22-gauge EUS
      needle, a guidewire was advanced antegrade across both the biliary stricture and
      the papilla. Subsequently, a rendezvous procedure was performed, allowing ERCP
      and stent placement. OBSERVATIONS: EUS-guided transhepatic cholangiography was
      performed in 6 patients, with successful rendezvous ERCP and stent placement in
      4, and transduodenal stent placement in another patient. Stent placement was
      unsuccessful in one patient, because of the inability to advance a guidewire into
      the common hepatic duct. There was no immediate complication of the procedures.
      CONCLUSIONS: EUS-guided transhepatic cholangiography can be used to access and to
      drain bile ducts that are obstructed by proximal, as well as distal lesions when
      ERCP is unsuccessful.

PMID- 15729254
TI  - EUS features of recurrent transitional cell bladder cancer metastatic to the GI
      tract.
AB  - BACKGROUND: Recurrent transitional cell bladder cancer (TCBC) can metastasize to
      the GI tract albeit uncommonly. This is the first report of the EUS appearance of
      metastatic TCBC to the GI tract. In addition to describing the EUS features of
      recurrent metastatic TCBC, this study determined the number of patients referred
      for evaluation of a primary GI luminal cancer in which EUS instead established
      the diagnosis of metastatic recurrent TCBC. METHODS: Patients referred from July
      2000 through April 2004 for EUS evaluation of a suspected primary GI luminal
      cancer were retrospectively reviewed. For patients with an established diagnosis
      of recurrent metastatic TCBC, EUS images were retrospectively reviewed to
      identify characteristic features. RESULTS: Of 2216 patients undergoing EUS to
      evaluate a suspected primary GI luminal cancer, 3 men (0.14%: 95% confidence
      interval [0.02%, 0.29%]) (mean age 67 years, range 54-74 years) were found
      instead to have recurrent metastatic TCBC involving the duodenum (n = 1) or
      rectum (n = 2). The patients presented a mean of 32 months after diagnosis of the
      primary TCBC with change in bowel habit (n = 1) and symptoms of bowel obstruction
      (n = 2). In each patient, initial endoscopy revealed circumferential luminal
      stenosis and mucosal erythema, but mucosal biopsy specimens revealed normal
      tissue. EUS demonstrated hypoechoic, symmetric, circumferential wall thickening,
      loss of deep wall layers, and pseudopodia-like extensions into the peri
      intestinal tissues. In the two patients with rectal involvement, no evidence of
      direct infiltration from the bladder bed was seen. EUS-guided FNA was diagnostic
      of metastatic TCBC in all patients. CONCLUSIONS: Although most cases of
      hypoechoic bowel-wall thickening and stenosis are from primary GI neoplasia,
      recurrent TCBC should be considered in patients with a history of this tumor.
      Correct diagnosis is important, because this allows selection of appropriate
      therapeutic interventions. Although firm EUS criteria for TCBC cannot be
      established based on findings in 3 patients, certain features may prove useful.
      EUS-guided FNA can confirm the diagnosis.

PMID- 15729255
TI  - Severe chest pain from an indwelling Bravo pH probe.

PMID- 15729256
TI  - Gastric tuberculosis presenting as a submucosal tumor.

PMID- 15729257
TI  - Duodenal and gastric Dieulafoy's lesions in a patient with type 2A von
      Willebrand's disease.

PMID- 15729258
TI  - Intraductal tubular adenocarcinoma of the pancreas diagnosed before surgery by
      transpapillary biopsy: case report and review.

PMID- 15729259
TI  - A case of mucin hypersecreting intraductal papillary carcinomas occurring
      simultaneously in liver and pancreas.

PMID- 15729260
TI  - EMR of a hyperplastic polyp arising in ectopic gastric mucosa in the cervical
      esophagus: case report.

PMID- 15729261
TI  - Pedunculated cap polyps preceding the development of cap polyposis: case report.

PMID- 15729262
TI  - Dissecting intramural hematoma of the esophagus after thrombolysis for myocardial
      infarction.

PMID- 15729263
TI  - Splenic infarction complicated by splenic artery occlusion after N-butyl-2
      cyanoacrylate injection for gastric varices: case report.

PMID- 15729264
TI  - Liver injury during PEG tube placement: report of two cases.

PMID- 15729265
TI  - Endoscopic minor papilla interventions in patients without pancreas divisum.

PMID- 15729266
TI  - Congenital esophageal duplication.

PMID- 15729267
TI  - Use of a transparent hood to facilitate photodynamic therapy of esophageal
      neoplasms.

PMID- 15729268
TI  - Safety and efficacy of ERCP in pregnancy.

PMID- 15729269
TI  - Argon plasma coagulation therapy for refractory ulcerative colitis.

PMID- 15729271
TI  - Pediatric ophthalmology in the Czech Republic.

PMID- 15729272
TI  - Bilateral medial rectus muscle recession for divergence insufficiency pattern
      esotropia.
AB  - PURPOSE: We have identified a group of mostly elderly patients characterized by
      chronic, slowly progressive esotropia with diplopia at distance. This study was
      undertaken to analyze the outcomes after bilateral medial rectus muscle
      recessions in this group of patients with a divergence insufficiency pattern of
      esotropia. MATERIALS AND METHODS: This is a retrospective consecutive case series
      of eight patients treated for divergence insufficiency pattern esotropia with
      bilateral medial rectus muscle recessions. RESULTS: Age at presentation was 44 to
      77 years (mean age, 60) and symptoms of diplopia at distance had been present
      between 3 and 30 years (mean, 12.6). Six patients had been managed with
      progressively larger amounts of base-out (BO) prism in their distance correction
      over an average of 12.5 years. Each patient had a manifest esotropia at distance
      and smaller or no deviation at near. The mean preoperative esodeviation was 20.4
      prism diopters (range, 12 to 35) at distance and 5.4 PD (range, 0 to 18) at near
      with a mean distance-near difference of 15.0 PD. Bilateral medial rectus muscle
      recession of 3.0 to 4.25 mm (mean 3.5) was performed on each patient. The mean
      postoperative esodeviation at distance was 3.4 PD (range 0 to 10) and the mean
      near deviation was 1.8 PD exophoria (range, 8 PD exophoria to 10 PD esotropia)
      with a mean distance-near difference of 5.1 PD. Three patients still required
      some prism in their spectacles for the relief of diplopia postoperatively (2 BO,
      8 BO, 10 BO). The mean follow-up period was 8.5 months (range, 6 weeks to 46
      months). CONCLUSIONS: Bilateral medial rectus muscle recession is an effective
      treatment for slowly progressive divergence insufficiency pattern esotropia in
      elderly patients. The reduction in the difference between the distance and near
      magnitudes of esodeviation afforded by this treatment suggests that a subtle loss
      of medial rectus muscle elasticity is the etiology.

PMID- 15729273
TI  - Lateral rectus resections in divergence palsy: results of long-term follow-up.
AB  - INTRODUCTION: Lateral rectus resections have been previously advocated as
      surgical options to treat patients with divergence palsy who do not respond well
      to prisms. This study was undertaken to review the results and long-term follow
      up of patients with divergence palsy who underwent lateral rectus resections at
      our institution. METHODS: Retrospective review of 29 patients (age 35-83 years)
      with divergence palsy. Five subjects underwent unilateral lateral rectus
      resection between 4.5 and 5.5 mm on adjustable suture and 24 subjects underwent
      bilateral lateral rectus resection between 3 and 7 mm on adjustable sutures.
      RESULTS: Preoperatively, all patients had diplopia at distance and an
      esodeviation, which was greater at distance (mean 14.7 +/- 5.1Delta) than at near
      (mean 4.7 +/- 3.5Delta). Twenty-five subjects had previously been treated with
      prisms. Postoperative follow-up period ranged from 6 to 96 months (mean 38.7 +/-
      27.3 months). The angle of deviation at distance was significantly reduced to 
      0.1 +/- 3.2Delta postoperatively ( P < 0.0001). The angle of deviation at near
      reduced significantly to -2.2 +/- 3.3Delta postoperatively ( P < 0.0001). No
      patient was overcorrected for near. Two patients experienced recurrent
      postoperative diplopia at distance subsequently at 1 and 4 years, which was
      corrected with prism glasses and lateral rectus re-resection. CONCLUSION: Lateral
      rectus resection in patients with divergence palsy is an effective and stable
      procedure in patients with divergence palsy over long-term follow-up periods,
      with minimal risk of overcorrections at near.

PMID- 15729274
TI  - Posttraumatic abducens to oculomotor nerve misdirection.
AB  - INTRODUCTION: Paradoxical patterns of extraocular muscle, eyelid, or pupillary
      movements can occur following injury between divisions of the oculomotor nerve,
      trigeminal and abducens nerves, and trigeminal and oculomotor nerves. We report
      three cases of unusual ocular motility and eyelid movements that are a result of
      aberrant connections between the abducens and oculomotor nerves. METHODS: Three
      patients with unusual eye movement abnormalities after trauma were studied. A
      complete ophthalmic examination plus neuroradiologic evaluation were performed.
      RESULTS: Each patient manifested an aberrant connection between the 6th and 3rd
      cranial nerves resulting in third nerve function during sixth nerve stimulation.
      Two patients demonstrated complete third nerve palsies except for adduction on
      attempted abduction. The third showed improved bilateral ptosis on abduction.
      CONCLUSIONS: The neuroanatomical abnormalities involve intraorbital structures in
      one patient and central nervous system pathways in the others. Explanations such
      as retrograde regeneration, ephaptic transmission, or denervation
      supersensitivity do not appear to explain these unusual eye movements. The most
      likely mechanism involves some form of peripheral neuronal misdirection. These
      rare sixth to third nerve misdirection cases add support to the "neuronal
      misdirection hypothesis" of aberrant eye movements after trauma.

PMID- 15729275
TI  - Case series of angle-closure glaucoma after laser treatment for retinopathy of
      prematurity.
AB  - PURPOSE: Laser photocoagulation is the current treatment standard for severe
      retinopathy of prematurity (ROP). Uncommon, but well recognized complications
      include cataract, and vitreous and retinal hemorrhage. Angle-closure glaucoma
      after laser photocoagulation for ROP is rare. The purpose of this study was to
      identify additional cases of angle-closure glaucoma following laser treatment for
      ROP. METHODS: Five eyes of four patients with angle-closure glaucoma following
      laser treatment for ROP were identified by three ophthalmologists at separate
      institutions between 1997 and 2001. Demographic and clinical data were obtained
      from medical records. Clinical and surgical findings associated with the
      diagnosis and management of angle-closure glaucoma following ROP laser were
      evaluated. RESULTS: The following data were collected (mean (range)): gestational
      age, 26.8 (24 to 29) weeks; birth weight, 833 (570 to 1062) g; age at laser
      treatment for ROP, 35 (33 to 37) weeks; number of laser burns, 1598 (930 to
      2400); and time to diagnosis of angle-closure glaucoma, 3.6 (2 to 5) weeks. Three
      of five eyes had objective data for intraocular pressure (IOP) and corneal
      diameter with mean IOP 41 mm Hg (35 to 44) and mean corneal diameter 11.1 mm
      (10.25 to 11.5). Initial treatment included topical and systemic medications.
      Three eyes required surgical intervention. Angle-closure resolved in all cases
      with normalization of IOP. Follow-up (5 months to 3.6 years) showed that affected
      eyes tended to be more myopic than unaffected fellow eyes (mean spherical
      equivalent -6.5 vs -4.7 diopters). CONCLUSIONS: Angle-closure glaucoma can
      develop following laser treatment for severe ROP. Medical, and frequently
      surgical, intervention provides effective management.

PMID- 15729276
TI  - Referral patterns for common amblyogenic conditions.
AB  - PURPOSE: The early detection and management of common pediatric ophthalmic
      problems is crucial to assure successful visual maturation and best potential for
      development of binocular vision. The referring physician plays a pivotal role in
      this process. This study was designed to investigate the prevailing referral
      patterns for common amblyogenic conditions in a defined geographic region.
      METHODS: We sent a short questionnaire to 300 pediatricians and 1500 family
      practitioners (FPs) in Minnesota, asking them to use a multiple choice system to
      indicate how long after diagnosis they would wait before referring a child to an
      ophthalmologist for exotropia, esotropia, ptosis, nystagmus, and abnormal red
      reflex. RESULTS: The response rate was 46.9% ( n = 117) for pediatricians and
      17.9% ( n = 240) for FPs. Of respondents, 64.6% of pediatricians and 50.2% of FPs
      would refer patients with exotropia within 2 months of diagnosis ( P < 0.001).
      For esotropia, 58.8% of pediatricians would refer within 2 months, while 38.6%
      would wait up to 12 months. In comparison, 48.7% of FPs would refer sooner, while
      47.9% would refer later. These differences in referral patterns for pediatricians
      and FPs were statistically significant ( P = 0.037). There was less variation for
      referral of ptosis, nystagmus, and abnormal red reflex. These referral patterns
      were unaffected by years in practice. CONCLUSIONS: Pediatricians referred
      patients with strabismus significantly more promptly than FPs. The majority of
      primary care providers (PCPs) appropriately timed their referrals for these
      amblyogenic conditions. However, many children continue to be referred late,
      underscoring the need for continued education of PCPs.

PMID- 15729277
TI  - Characteristics and outcomes of strabismus surgery after orbital decompression
      for thyroid eye disease.
AB  - PURPOSE: To compare characteristics and outcomes of strabismus surgery in
      patients who have undergone orbital decompression for thyroid eye disease with
      those who have not. SUBJECTS AND METHODS: A chart review of all patients with
      thyroid eye disease requiring strabismus surgery in one physician's practice.
      RESULTS: There were 36 patients in the decompression group (DG) and 14 patients
      in the no-decompression group (NDG). There was a significantly greater amount of
      preoperative esotropia in the DG ( P = 0.02). There was an increased incidence of
      A-pattern in the DG ( P = 0.09). There was a slightly higher number of operated
      muscles in the DG ( P = 0.005). A good or excellent outcome was achieved in 93%
      of the NDG and in 94% of the DG ( P = 0.83). DISCUSSION: Previous studies suggest
      that patients requiring orbital decompression have a more complex thyroid eye
      disease and a lower success rate after strabismus surgery. Our findings suggest
      that this is not necessarily the case, and the difference in surgical success
      rates between the studies may in part be due to orbital decompression technique
      or indication. CONCLUSION: In this series, using a fixed suture technique,
      outcomes of strabismus surgery in patients with thyroid eye disease who underwent
      orbital decompression are similar to those who did not.

PMID- 15729278
TI  - Measurement of stereoacuity outcomes at ages 1 to 24 months: Randot Stereocards.
AB  - PURPOSE: The aim of the present study was to develop a simple, quick, and
      portable random dot stereoacuity test for measurement of binocular sensory
      outcomes during the first 24 months of life. METHODS: Vertical bar random dot
      vectographs were adapted for presentation in a "Teller Acuity Card" format,
      called the "Randot Stereocards." A forced-choice preferential looking protocol
      was used. Study participants included 386 healthy, term infants and children
      (normative cohort; age range: 1 month to 8 years) and 280 patients with common
      pediatric ophthalmic disorders (patient cohort; age range: 5 months to 9 years).
      RESULTS: Overall, the success rate for test completion in the normative cohort
      was 91.3%. By 4 months of age, normal infants' mean stereoacuity was about 600''
      and, by 6 months, 200''. Mean stereoacuity further improved to about 100'' by 12
      months and 70'' by 18 months. Normative results were similar to published data
      obtained with laboratory-based stereoacuity tests. Randot Stereocard data from
      normal children aged 2 to 6 years were similar to published normative data for
      the Preschool Randot Stereoacuity Test. In the patient cohort, concordance
      between the Randot Stereocards and the Preschool Randot Test was 87%; concordance
      between the Randot Stereocards and the Randot Test was 84%. CONCLUSION: The
      Randot Stereocards provide a simple, reliable, and valid method of obtaining a
      quantitative assessment of binocular vision in children up to 24 months of age
      for use in clinical trials and in clinical management.

PMID- 15729279
TI  - Suppression of metabolic activity caused by infantile strabismus and strabismic
      amblyopia in striate visual cortex of macaque monkeys.
AB  - INTRODUCTION: Suppression is a major sensorial abnormality in humans and monkeys
      with infantile strabismus. We previously reported evidence of metabolic
      suppression in the visual cortex of strabismic macaques, using the mitochondrial
      enzyme cytochrome oxidase as an anatomic label. The purpose of this study was to
      further elucidate alterations in cortical metabolic activity, with or without
      amblyopia. MATERIALS AND METHODS: Six macaque monkeys were used in the
      experiments (four strabismic and two control). Three of the strabismic monkeys
      had naturally occurring, infantile strabismus (two esotropic, one exotropic). The
      fourth strabismic monkey had infantile microesotropia induced by alternating
      monocular occlusion in the first months of life. Ocular motor behaviors and
      visual acuity were tested after infancy in each animal, and development of
      stereopsis was recorded during infancy in one strabismic and one control monkey.
      Ocular dominance columns (ODCs) of the striate visual cortex (area V1) were
      labeled using cytochrome oxidase (CO) histochemistry alone, or CO in conjunction
      with an anterograde tracer ([H 3 ]proline or WGA-HRP) injected into one eye.
      RESULTS: Each of the strabismic monkeys showed inequalities of metabolic activity
      in ODCs of opposite ocularity, visible as rows of lighter CO staining,
      corresponding to ODCs of lower metabolic activity, alternating with rows of
      darker CO staining, corresponding to ODCs of higher metabolic activity. In
      monkeys who had infantile strabismus and unilateral amblyopia, lower metabolic
      activity was found in (suppressed) ODCs driven by the nondominant eye in each
      hemisphere. In monkeys who had infantile esotropia and alternating fixation (no
      amblyopia), metabolic activity was lower in ODCs driven by the ipsilateral eye in
      each hemisphere. The suppression included a monocular core zone at the center of
      ODCs and binocular border zones at the boundaries of ODCs. This suppression was
      not evident in the monocular lamina of the LGN, indicating an intracortical
      rather than subcortical mechanism. CONCLUSION: Suppression of metabolic activity
      in ODCs of V1 differs depending upon whether infantile strabismus is alternating
      or occurs in conjunction with unilateral amblyopia. Our findings reinforce the
      principle that unrepaired strabismus promotes abnormal competition in V1,
      observable as interocular suppression of ODCs.

PMID- 15729280
TI  - Comparison of visual acuity levels in pediatric patients with amblyopia using
      Wright figures, Allen optotypes, and Snellen letters.
AB  - PURPOSE: To compare and correlate the clinical performance of Wright figures in
      visual acuity assessments of pediatric patients with amblyopia to those obtained
      through Allen cards and Snellen letters. SUBJECTS AND METHODS: Best-corrected
      visual acuity of 26 amblyopic children were measured with the Wright figures(c),
      Snellen letters, and isolated Allen optotypes, respectively. Amblyopia was
      defined as two lines of visual acuity difference or a visual acuity level of
      20/30 or lower as determined by Snellen chart. The results were evaluated for
      statistical intergroup differences using the Wilks' Lambda multivariate analysis
      of variance and for correlation using the Pearson correlation coefficient test.
      RESULTS: The mean age of the subjects was 8.27 +/- 2.46 years (range: 5 to 15
      years). The mean logMAR values for the Wright figures(c), Snellen letters, and
      Allen optotypes were 0.40 +/- 0.20, 0.47 +/- 0.23, and 0.29 +/- 0.28,
      respectively. When compared with Snellen letters, the Wright figures correlated
      to a higher degree ( r = 0.46, P < 0.001) than Allen optotypes ( r = 0.67, P <
      0.001). With a visual acuity of 20/40 or worse on Snellen letter testing, the
      sensitivity of Wright figures(c) and Allen cards in diagnosing amblyopic eyes was
      87.0 and 56.5%, respectively ( P = 0.016). CONCLUSIONS: Wright figures, designed
      primarily to evaluate the vision in the preliterate pediatric population,
      correlate more closely to Snellen letters and have a higher rate of correctly
      identifying amblyopia than isolated Allen optotypes in pediatric patients.

PMID- 15729281
TI  - Isolated subconjunctival hemorrhages in nonaccidental trauma.
AB  - PURPOSE: To establish child abuse as part of the differential diagnosis of
      isolated bilateral subconjunctival hemorrhages in infants. METHODS: To review
      three cases of nonaccident trauma initially presenting with isolated bilateral
      subconjunctival hemorrhages as the only significant clinical finding. RESULTS:
      Ophthalmic examination in cases 1 and 2 were entirely normal except for the large
      bilateral subconjunctival hemorrhages. Hematological parameters were normal in
      all three infants. Initial radiological findings were normal in case 1 but
      multiple healing rib fractures were identified when the chest X-ray was repeated
      3 weeks later. Case 2 had skin and skeletal X-ray findings compatible with abuse
      at time of presentation to the ophthalmologist. Case 3 was admitted to hospital
      for multiple unexplained limb fractures but had been seen 2 weeks prior for
      poorly explained bilateral isolated subconjunctival hemorrhages and facial
      petechiae. CONCLUSION: Nonaccidental trauma should be considered in the
      differential diagnosis of bilateral isolated subconjunctival hemorrhages in
      infants especially if associated with facial petechiae. These isolated
      subconjunctival hemorrhages may be part of the traumatic asphyxia syndrome caused
      by severe, prolonged compression of the child's chest and upper abdomen.
      Appropriate assessment includes a complete ophthalmic and pediatric examination
      as well as hematological testing and imaging studies. If the coagulation profile
      and initial imaging studies are normal yet there remains a high suspicion of
      abuse, an immediate nuclear scan or a repeat skeletal survey or chest film 2
      weeks later is indicated.

PMID- 15729282
TI  - A child with multiple absent extraocular muscles.

PMID- 15729283
TI  - Periodic alternating gaze deviation associated with schizencephaly and optic
      nerve hypoplasia.

PMID- 15729284
TI  - Congenital upper eyelid entropion.

PMID- 15729285
TI  - Letter of apology. Cerebral ischemia and reperfusion: the pathophysiologic
      concept as a basis for clinical therapy.

PMID- 15729286
TI  - Fabrication, falsification and plagiarism and clearly involves intention to
      deceive.

PMID- 15729287
TI  - Cerebral oxygenation during postasphyxial seizures in near-term fetal sheep.
AB  - After exposure to asphyxia, infants may develop both prolonged, clinically
      evident seizures and shorter, clinically silent seizures; however, their effect
      on cerebral tissue oxygenation is unclear. We therefore examined the hypothesis
      that the increase in oxygen delivery during postasphyxial seizures might be
      insufficient to meet the needs of increased metabolism, thus causing a fall in
      tissue oxygenation, in unanesthetized near-term fetal sheep in utero (gestational
      age 125+/-1 days). Fetuses were administered an infusion of the specific
      adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, followed by
      10 mins of asphyxia induced by complete umbilical cord occlusion. The fetuses
      then recovered for 3 days. Sixty-one episodes of electrophysiologically defined
      seizures were identified in five fetuses. Tissue PO(2) (tPO(2)) did not change
      significantly during short seizures (<3.5 mins), 5.2+/-0.2 versus baseline 5.6+/
      0.1 mm Hg (NS), but fell to 2.2+/-0.2 mm Hg during seizures lasting more than 3.5
      mins (P<0.001). During prolonged seizures, cortical blood flow did not begin to
      increase until tPO(2) had begun to fall, and then rose more slowly than the
      increase in metabolism, with a widening of the brain to blood temperature
      gradient. In conclusion, in the immature brain, during prolonged, but not short
      seizures, there is a transient mismatch between cerebral blood flow and
      metabolism leading to significant cerebral deoxygenation.

PMID- 15729288
TI  - Tumor necrosis factor-alpha neutralization reduced cerebral edema through
      inhibition of matrix metalloproteinase production after transient focal cerebral
      ischemia.
AB  - After focal cerebral ischemia, tumor necrosis factor-alpha deteriorates cerebral
      edema and survival rate. Therefore, tumor necrosis factor-alpha neutralization
      could reduce cerebral microvascular permeability in acute cerebral ischemia. Left
      middle cerebral artery occlusion for 120 mins followed by reperfusion was
      performed with the thread method under halothane anesthesia in Sprague-Dawley
      rats. Antirat tumor necrosis factor-alpha neutralizing monoclonal antibody with a
      rat IgG Fc portion (15 mg/kg) was infused intravenously right after reperfusion.
      Stroke index score, infarct volume, cerebral specific gravity, and the endogenous
      expression of tumor necrosis factor-alpha, matrix metalloproteinase (MMP)-2, MMP
      9, and membrane type 1-MMP in the brain tissue were quantified in the ischemic
      and matched contralateral nonischemic hemisphere. In the antitumor necrosis
      factor-alpha neutralizing antibody-treated rats, infarct volume was significantly
      reduced (P=0.014, n=7; respectively), and cerebral specific gravity was
      dramatically increased in the cortex and caudate putamen (P<0.001, n=7;
      respectively) in association with a reduction in MMP-9 and membrane type 1-MMP
      upregulation. Tumor necrosis factor-alpha in the brain tissue was significantly
      elevated in the ischemic hemisphere 6 h after reperfusion in the nonspecific IgG
      treated rats (P=0.021, n=7) and was decreased in the antitumor necrosis factor
      alpha neutralizing antibody-treated rats (P=0.001, n=7). Postreperfusion
      treatment with antirat tumor necrosis factor-alpha neutralizing antibody reduced
      brain infarct volume and cerebral edema, which is likely mediated by a reduction
      in MMP upregulation.

PMID- 15729289
TI  - Hypoxic preconditioning and tolerance via hypoxia inducible factor (HIF) 1alpha
      linked induction of P450 2C11 epoxygenase in astrocytes.
AB  - The brain's adaptive response to ischemic preconditioning (IPC) is mediated in
      part via hypoxia inducible factor (HIF)-responsive genes. We previously showed
      that IPC induces cytochrome P450 2C11 expression in the brain, associated with
      protection from stroke. Cytochrome P450 2C11 is an arachidonic acid (AA)
      epoxygenase expressed in astrocytes, which metabolizes AA to epoxyeicosatrienoic
      acids (EETs). We tested the hypotheses that hypoxic preconditioning (HPC) induces
      2C11 expression in astrocytes via HIF-1alpha, and that the P450 epoxygenase
      pathway contributes to enhanced astrocyte tolerance to ischemia-like injury
      induced by oxygen-glucose deprivation (OGD). Primary cultured astrocytes were
      incubated under normoxic or hypoxic conditions for 1, 3, 6, 24, or 48 h, and
      protein levels of P450 2C11 and HIF-1alpha were measured by Western blotting.
      Additionally, 2C11 mRNA was measured by Northern blotting, and binding of HIF
      1alpha to 2C11 promoter was evaluated using electrophoretic mobility shift assay
      (EMSA) with 2C11 promoter DNA containing putative HIF-binding sites. Levels of
      2C11 mRNA and protein were significantly increased starting at 3 and 6 h of
      hypoxia, respectively. The increase in 2C11 expression was preceded by an
      increase in HIF-1alpha protein at 1 h of hypoxia, and EMSA showed a specific and
      direct interaction between 2C11 promoter DNA and HIF-1alpha in nuclear extracts
      from astrocytes. HPC and EETs reduced astrocyte cell death, and P450 epoxygenase
      inhibition prevented protection by HPC. We conclude that HPC induces tolerance in
      astrocytes, at least in part, via HIF-1alpha-linked upregulation of P450 2C11.

PMID- 15729290
TI  - Angiotensin II AT1 receptor blockade abolishes brain microvascular inflammation
      and heat shock protein responses in hypertensive rats.
AB  - Endothelial dysfunction and inflammation enhance vulnerability to hypertensive
      brain damage. To explore the participation of Angiotensin II (Ang II) in the
      mechanism of vulnerability to cerebral ischemia during hypertension, we examined
      the expression of inflammatory factors and the heat shock protein (HSP) response
      in cerebral microvessels from spontaneously hypertensive rats and their
      normotensive controls, Wistar Kyoto rats. We treated animals with vehicle or the
      Ang II AT(1) receptor antagonist candesartan, 0.3 mg/kg/day, via subcutaneously
      implanted osmotic minipumps for 4 weeks. Spontaneously hypertensive rats
      expressed higher Angiotensin II AT(1) receptor protein and mRNA than normotensive
      controls. Candesartan decreased the macrophage infiltration and reversed the
      enhanced tumor necrosis factor-alpha and interleukin-1beta mRNA and nuclear
      factor-kappaB in microvessels in hypertensive rats. The transcription of many HSP
      family genes, including HSP60, HSP70 and HSP90, and heat shock factor-1 was
      higher in hypertensive rats and was downregulated by AT(1) receptor blockade. Our
      results suggest a proinflammatory action of Ang II through AT(1) receptor
      stimulation in cerebral microvessels during hypertension, and very potent
      antiinflammatory effects of the Ang II AT(1) receptor antagonist. These compounds
      might be considered as potential therapeutic agents against ischemic and
      inflammatory diseases of the brain.

PMID- 15729291
TI  - Cerebral endothelial cell apoptosis after ischemia-reperfusion: role of PARP
      activation and AIF translocation.
AB  - Cerebral ischemia-reperfusion leads to vascular dysfunction characterized by
      endothelial cell injury or death. In the present study, we used an in vitro model
      to elucidate mechanisms of human brain microvascular endothelial cell (HBMEC)
      injury after episodic ischemia-reperfusion. Near-confluent HBMEC cultures were
      exposed to intermittent hypoxia-reoxygenation (HX/RO) and, at different recovery
      time points, cell viability was assessed by the MTT assay, apoptotic death by
      fluorescence microscopy of terminal deoxynucleotidyl transferase-mediated 2'
      deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-positive cells, and
      nuclear translocation of apoptosis-inducing factor (AIF) and cleavage of poly(ADP
      ribose) polymerase-1 (PARP-1) by immunoblotting of subcellular fractions.
      Reductions in HBMEC viability were proportional to the number of HX/RO cycles,
      and not the total duration of hypoxia. Using four cycles of 1-h HX with 1 h of
      intervening normoxic RO, cell viability was reduced 30% to 40% between 12 and 48
      h. Treatment with the PARP-1 inhibitors 3-aminobenzamide or 4-amino-1,8
      naphthalimide during the insult improved HBMEC viability at 24 h after insult,
      and resulted in dose-dependent reductions in TUNEL-positivity at 16 h after
      insult, but not if these treatments were delayed by 4 h. HX/RO-induced increases
      in nuclear AIF translocation, as well as PARP-1 cleavage, were also reduced dose
      dependently at 4 h after insult by the inhibitors. The caspase inhibitor z-VAD
      fmk blocked PARP-1 cleavage, but did not affect AIF translocation and was only
      modestly cytoprotective. These findings indicate that PARP-1 activation and a
      PARP-1-dependent, caspase-independent, nuclear translocation of AIF contribute to
      apoptotic cerebral endothelial cell death after ischemia-reperfusion,
      underscoring the potential for ischemic microvascular protection by inhibiting
      PARP activation or preventing AIF translocation.

PMID- 15729292
TI  - PET studies of net blood-brain clearance of FDOPA to human brain: age-dependent
      decline of [18F]fluorodopamine storage capacity.
AB  - Conventional methods for the graphical analysis of 6-[(18)F]fluorodopa
      (FDOPA)/positron emission tomography (PET) recordings (K(in)(app)) may be prone
      to negative bias because of oversubtraction of the precursor pool in the region
      of interest, and because of diffusion of decarboxylated FDOPA metabolites from
      the brain. These effects may reduce the sensitivity of FDOPA/PET for the
      detection of age-related changes in dopamine innervations. To test for these
      biasing effects, we have used a constrained compartmental analysis to calculate
      the brain concentrations of the plasma metabolite 3-O-methyl-FDOPA (OMFD) during
      120 mins of FDOPA circulation in healthy young, healthy elderly, and Parkinson's
      disease subjects. Calculated brain OMFD concentrations were subtracted frame-by
      frame from the dynamic PET recordings, and maps of the FDOPA net influx to brain
      were calculated assuming irreversible trapping (K(app)). Comparison of K(in)(app)
      and K(app) maps revealed a global negative bias in the conventional estimates of
      FDOPA clearance. The present OMFD subtraction method revealed curvature in plots
      of K(app) at early times, making possible the calculation of the corrected net
      influx (K) and also the rate constant for diffusion of decarboxylated metabolites
      from the brain (k(loss)). The effective distribution volume (EDV(2); K/k(loss))
      for FDOPA, an index of dopamine storage capacity in brain, was reduced by 85% in
      putamen of patients with Parkinson's disease, and by 58% in the healthy elderly
      relative to the healthy young control subjects. Results of the present study
      support claims that storage capacity for dopamine in both caudate and putamen is
      more profoundly impaired in patients with Parkinson's disease than is the
      capacity for DOPA utilization, calculated by conventional FDOPA net influx plots.
      The present results furthermore constitute the first demonstration of an
      abnormality in the cerebral utilization of FDOPA in caudate and putamen as a
      function of normal aging, which we attribute to loss of vesicular storage
      capacity.

PMID- 15729294
TI  - Initial oligemia with capillary flow stop followed by hyperemia during K+-induced
      cortical spreading depression in rats.
AB  - Local cerebral blood volume (CBV) and capillary flow changes in regions of
      depolarizing neurons during K(+)-induced cortical spreading depression (CSD) in
      the cerebral cortex of alpha-chloralose-urethane-anesthetized rats were examined
      employing a transillumination (550 nm) video system. Capillary flow was
      calculated as the reciprocal of mean transit times of blood in pixels of 40
      microm x 40 microm, each of which contains a few capillaries. Potassium
      microinjection into the cortex evoked repetitive wave-ring spreads of oligemia at
      a speed of ca. 2.33 +/- 0.48 mm/min. During the spread of CSD, tracer (either
      saline or carbon black) was injected into the internal carotid artery. Colocated
      with the oligemic wave, we detected capillary flow stop as evidenced by
      disappearance of the hemodilution curves. At any location in the region of
      interest within the cerebral cortex, we observed cyclic changes of capillary flow
      stop/hyperperfusion in synchrony with oligemia/hyperemia fluctuations. The
      initial flow stop and oligemia were ascribed to capillary compression by
      astroglial cell swelling, presumably at the pericapillary endfeet, since the
      oligemia occurred before larger vessel changes. We conclude that local
      depolarizing neurons can decrease adjacent capillary flow directly and
      immediately, most likely via astroglial cell swelling, and that the flow stop
      triggers upstream arteriolar dilatation for capillary hyperperfusion.

PMID- 15729293
TI  - A dopamine D4 receptor antagonist attenuates ischemia-induced neuronal cell
      damage via upregulation of neuronal apoptosis inhibitory protein.
AB  - Neuronal apoptosis inhibitory protein (NAIP/BIRC1), the inhibitor of apoptosis
      protein (IAP) family member, suppresses neuronal cell death induced by a variety
      of insults, including cell death from ischemia and stroke. The goal of the
      present study was to develop an efficient method for identification of compounds
      with the ability to upregulate endogenous NAIP and to determine the effects on
      these compounds on the cellular response to ischemia. A novel NAIP-enzyme-linked
      immunosorbent assay (ELISA)-based in vitro drug-screening system is established.
      Use of this system identified an antagonist of dopamine D4 receptor, termed L
      745,870, with a potent NAIP upregulatory effect. L-745,870-mediated NAIP
      upregulation in neuronal and nonneuronal cultured cells resulted in decreased
      vulnerability to oxidative stress-induced apoptosis. Reducing NAIP expression via
      RNA interference techniques resulted in prevention of L-745,870-mediated
      protection from oxidative stress. Further, systemic administration of L-745,870
      attenuated ischemia-induced damage of the hippocampal CA1 neurons and upregulated
      NAIP expression in the rescued hippocampal CA1 neurons in a gerbil model. These
      data suggest that the NAIP upregulating compound, L-745,870, has therapeutic
      potential in acute ischemic disorders and that our NAIP-ELISA-based drug
      screening may facilitate the discovery of novel neuroprotective compounds.

PMID- 15729295
TI  - Role of p53 and apoptosis in cerebral vasospasm after experimental subarachnoid
      hemorrhage.
AB  - Our previous studies indicate that apoptosis in endothelial cells of major
      cerebral arteries contributes to cerebral vasospasm after subarachnoid hemorrhage
      (SAH). This study examined the pathologic roles of tumor suppressor p-53 in
      cerebral vasospasm using an established dog double-hemorrhage model. Twenty
      mongrel dogs were divided into four groups: (1) control, (2) SAH, (3) SAH+DMSO
      (vehicle), and (4) SAH+pifithrin-alpha (PFT) (p53 inhibitor). The p53 inhibitor
      (200 nmol/L) was injected into the cisterna magna daily from Day 0 through Day 3.
      Angiogram was performed on Day 0 and Day 7. Western blot, cell proliferation
      assay, histology, and TUNEL staining were conducted on the basilar arteries
      collected on Day 7 after SAH. The arterial diameter on Day 7 was 42%+/-4%, 40%+/
      5%, and 59%+/-4% for SAH, SAH+DMSO, and SAH+PFT, respectively. In addition,
      positive staining of TUNEL and increased protein expression of p53, Bax, and PCNA
      in the basilar artery were observed on Day 7. PFT suppressed apoptosis in
      endothelial cells and proliferation in smooth muscle cells, and attenuated
      angiographic vasospasm. In conclusion, p53 may be a key factor in endothelial
      apoptosis and smooth muscle proliferation after SAH. Inhibition of p53 may
      potentially reduce or even prevent cerebral vasospasm.

PMID- 15729298
TI  - Making sense of the world.

PMID- 15729296
TI  - CB1 cannabinoid receptors are involved in neuroprotection via NF-kappa B
      inhibition.
AB  - We reported earlier that closed head injury (CHI) in mice causes a sharp
      elevation of brain 2-arachidonoylglycerol (2-AG) levels, and that exogenous 2-AG
      reduces brain edema, infarct volume and hippocampal death and improved clinical
      recovery after CHI. The beneficial effect of 2-AG was attenuated by SR141716A, a
      CB1 cannabinoid receptor antagonist, albeit at relatively high doses. In the
      present study, we further explored the role of CB1 receptors in mediating 2-AG
      neuroprotection. CB1 receptor knockout mice (CB1-/-) showed minor spontaneous
      recovery at 24 h after CHI, in contrast to the significant improvement in
      neurobehavioral function seen in wild-type (WT) mice. Moreover, administration of
      2-AG did not improve neurological performance and edema formation in the CB1-/-
      mice. In addition, 2-AG abolished the three- to four-fold increase of nuclear
      factor kappaB (NF-kappa B) transactivation, at 24 h after CHI in the WT mice,
      while it had no effect on NF-kappaB in the CB1-/- mice, which was as high as in
      the WT vehicle-treated mice. We thus propose that 2-AG exerts its neuroprotection
      after CHI, at least in part, via CB1 receptor-mediated mechanisms that involve
      inhibition of intracellular inflammatory signaling pathways.

PMID- 15729299
TI  - Tests in Tokyo reveal flaws in Vietnam's bird flu surveillance.

PMID- 15729300
TI  - New York draws fire over case of drug-resistant HIV.

PMID- 15729301
TI  - Flu gene discovery prompts calls for tighter monitoring.

PMID- 15729302
TI  - Russian security arrests institute head for spying.

PMID- 15729303
TI  - Global observation project gets green light.

PMID- 15729305
TI  - Speech transcript stokes opposition to Harvard head.

PMID- 15729304
TI  - Vioxx may go back on sale after scraping past FDA panel.

PMID- 15729306
TI  - Nitrogen study fertilizes fears of pollution.

PMID- 15729309
TI  - Around the world in three square meals.

PMID- 15729308
TI  - Dietary advice: flash in the pan?

PMID- 15729310
TI  - Food FAQs.

PMID- 15729311
TI  - Online submission makes authors do all the work.

PMID- 15729312
TI  - Best way to protect rock art is to leave it alone.

PMID- 15729313
TI  - Climate blog could score with newer hockey stick.

PMID- 15729319
TI  - Schrodinger's mousetrap. Part 6.

PMID- 15729314
TI  - Vital resource should be open to all physicists.

PMID- 15729320
TI  - Elephant breakdown.

PMID- 15729321
TI  - Climate change: snow maker for the ice ages.

PMID- 15729322
TI  - Hearing: aid from hair force.

PMID- 15729323
TI  - Photonics: expect more delays.

PMID- 15729324
TI  - Immunology: guide for a cell-fate decision.

PMID- 15729325
TI  - Planetary science: being there.

PMID- 15729327
TI  - Human immunodeficiency virus: refolding the envelope.

PMID- 15729328
TI  - Obituary: Eduard Kellenberger (1920-2004).

PMID- 15729330
TI  - Materials chemistry: a synthetic enamel for rapid tooth repair.
AB  - The conventional treatment of dental caries involves mechanical removal of the
      affected part and filling of the hole with a resin or metal alloy. But this
      method is not ideal for tiny early lesions because a disproportionate amount of
      healthy tooth must be removed to make the alloy or resin stick. Here we describe
      a dental paste of synthetic enamel that rapidly and seamlessly repairs early
      caries lesions by nanocrystalline growth, with minimal wastage of the natural
      enamel.

PMID- 15729331
TI  - Ecology: a niche for cyanobacteria containing chlorophyll d.
AB  - The cyanobacterium known as Acaryochloris marina is a unique phototroph that uses
      chlorophyll d as its principal light-harvesting pigment instead of chlorophyll a,
      the form commonly found in plants, algae and other cyanobacteria; this means that
      it depends on far-red light for photosynthesis. Here we demonstrate
      photosynthetic activity in Acaryochloris-like phototrophs that live underneath
      minute coral-reef invertebrates (didemnid ascidians) in a shaded niche enriched
      in near-infrared light. This discovery clarifies how these cyanobacteria are able
      to thrive as free-living organisms in their natural habitat.

PMID- 15729332
TI  - North Pacific seasonality and the glaciation of North America 2.7 million years
      ago.
AB  - In the context of gradual Cenozoic cooling, the timing of the onset of
      significant Northern Hemisphere glaciation 2.7 million years ago is consistent
      with Milankovitch's orbital theory, which posited that ice sheets grow when polar
      summertime insolation and temperature are low. However, the role of moisture
      supply in the initiation of large Northern Hemisphere ice sheets has remained
      unclear. The subarctic Pacific Ocean represents a significant source of water
      vapour to boreal North America, but it has been largely overlooked in efforts to
      explain Northern Hemisphere glaciation. Here we present alkenone unsaturation
      ratios and diatom oxygen isotope ratios from a sediment core in the western
      subarctic Pacific Ocean, indicating that 2.7 million years ago late-summer sea
      surface temperatures in this ocean region rose in response to an increase in
      stratification. At the same time, winter sea surface temperatures cooled, winter
      floating ice became more abundant and global climate descended into glacial
      conditions. We suggest that the observed summer warming extended into the autumn,
      providing water vapour to northern North America, where it precipitated and
      accumulated as snow, and thus allowed the initiation of Northern Hemisphere
      glaciation.

PMID- 15729333
TI  - The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell
      lineage commitment.
AB  - Development of immature T-cell precursors (thymocytes) to either the CD4 helper
      or CD8 killer T-cell lineages correlates precisely with their T-cell receptor
      specificity for major histocompatibility complex class II or class I molecules,
      respectively, indicating that the process is carefully regulated. Although
      intensively studied owing to its importance in determining the composition of the
      mature T-cell compartment and as a general model of binary lineage decisions, the
      underlying molecular pathways remain obscure. We have previously reported a
      spontaneous mouse mutant (HD (helper deficient) mice) in which lineage commitment
      is specifically perturbed without affecting positive selection. Here we show that
      a point mutation in the zinc finger transcription factor Th-POK (T-helper
      inducing POZ/Kruppel-like factor) is responsible for redirection of class-II
      restricted thymocytes to the CD8 lineage in HD mice. Furthermore, we demonstrate
      that constitutive expression of this factor during thymic development leads to
      redirection of class-I-restricted thymocytes to the CD4 lineage, indicating that
      Th-POK is a master regulator of lineage commitment.

PMID- 15729336
TI  - Raman injection laser.
AB  - Stimulated Raman scattering is a nonlinear optical process that, in a broad
      variety of materials, enables the generation of optical gain at a frequency that
      is shifted from that of the incident radiation by an amount corresponding to the
      frequency of an internal oscillation of the material. This effect is the basis
      for a broad class of tunable sources known as Raman lasers. In general, these
      sources have only small gain (approximately 10(-9) cm W(-1)) and therefore
      require external pumping with powerful lasers, which limits their applications.
      Here we report the realization of a semiconductor injection Raman laser designed
      to circumvent these limitations. The physics underlying our device differs in a
      fundamental way from existing Raman lasers: it is based on triply resonant
      stimulated Raman scattering between quantum-confined states within the active
      region of a quantum cascade laser that serves as an internal optical pump--the
      device is driven electrically and no external laser pump is required. This leads
      to an enhancement of orders of magnitude in the Raman gain, high conversion
      efficiency and low threshold. Our lasers combine the advantages of nonlinear
      optical devices and of semiconductor injection lasers, and could lead to a new
      class of compact and wavelength-agile mid-and far-infrared light sources.

PMID- 15729334
TI  - Structure of an unliganded simian immunodeficiency virus gp120 core.
AB  - Envelope glycoproteins of human and simian immunodeficiency virus (HIV and SIV)
      undergo a series of conformational changes when they interact with receptor (CD4)
      and co-receptor on the surface of a potential host cell, leading ultimately to
      fusion of viral and cellular membranes. Structures of fragments of gp120 and gp41
      from the envelope protein are known, in conformations corresponding to their post
      attachment and postfusion states, respectively. We report the crystal structure,
      at 4 A resolution, of a fully glycosylated SIV gp120 core, in a conformation
      representing its prefusion state, before interaction with CD4. Parts of the
      protein have a markedly different organization than they do in the CD4-bound
      state. Comparison of the unliganded and CD4-bound structures leads to a model for
      events that accompany receptor engagement of an envelope glycoprotein trimer. The
      two conformations of gp120 also present distinct antigenic surfaces. We identify
      the binding site for a compound that inhibits viral entry.

PMID- 15729335
TI  - Enhanced atmospheric loss on protoplanets at the giant impact phase in the
      presence of oceans.
AB  - The atmospheric compositions of Venus and Earth differ significantly, with the
      venusian atmosphere containing about 50 times as much 36Ar as the atmosphere on
      Earth. The different effects of the solar wind on planet-forming materials for
      Earth and Venus have been proposed to account for some of this difference in
      atmospheric composition, but the cause of the compositional difference has not
      yet been fully resolved. Here we propose that the absence or presence of an ocean
      at the surface of a protoplanet during the giant impact phase could have
      determined its subsequent atmospheric amount and composition. Using numerical
      simulations, we demonstrate that the presence of an ocean significantly enhances
      the loss of atmosphere during a giant impact owing to two effects: evaporation of
      the ocean, and lower shock impedance of the ocean compared to the ground.
      Protoplanets near Earth's orbit are expected to have had oceans, whereas those
      near Venus' orbit are not, and we therefore suggest that remnants of the noble
      gas rich proto-atmosphere survived on Venus, but not on Earth. Our proposed
      mechanism explains differences in the atmospheric contents of argon, krypton and
      xenon on Venus and Earth, but most of the neon must have escaped from both
      planets' atmospheres later to yield the observed ratio of neon to argon.

PMID- 15729337
TI  - Quantum chemical calculations show that the uranium molecule U2 has a quintuple
      bond.
AB  - Covalent bonding is commonly described by Lewis's theory, with an electron pair
      shared between two atoms constituting one full bond. Beginning with the valence
      bond description for the hydrogen molecule, quantum chemists have further
      explored the fundamental nature of the chemical bond for atoms throughout the
      periodic table, confirming that most molecules are indeed held together by one
      electron pair for each bond. But more complex binding may occur when large
      numbers of atomic orbitals can participate in bond formation. Such behaviour is
      common with transition metals. When involving heavy actinide elements, metal
      metal bonds might prove particularly complicated. To date, evidence for actinide
      actinide bonds is restricted to the matrix-isolation of uranium hydrides,
      including H2U-UH2, and the gas-phase detection and preliminary theoretical study
      of the uranium molecule, U2. Here we report quantum chemical calculations on U2,
      showing that, although the strength of the U2 bond is comparable to that of other
      multiple bonds between transition metals, the bonding pattern is unique. We find
      that the molecule contains three electron-pair bonds and four one-electron bonds
      (that is, 10 bonding electrons, corresponding to a quintuple bond), and two
      ferromagnetically coupled electrons localized on one U atom each-so all known
      covalent bonding types are contributing.

PMID- 15729338
TI  - Lithospheric structure of the Rio Grande rift.
AB  - A high-resolution, regional passive seismic experiment in the Rio Grande rift
      region of the southwestern United States has produced new images of upper-mantle
      velocity structure and crust-mantle topography. Synthesizing these results with
      geochemical and other geophysical evidence reveals highly symmetric lower-crustal
      and upper-mantle lithosphere extensional deformation, suggesting a pure-shear
      rifting mechanism for the Rio Grande rift. Extension in the lower crust is
      distributed over a region four times the width of the rift's surface expression.
      Here we propose that the laterally distributed, pure shear extension is a
      combined effect of low strain rate and a regionally elevated geotherm, possibly
      abetted by pre-existing lithospheric structures, at the time of rift initiation.
      Distributed extension in the lower crust and mantle has induced less concentrated
      vertical mantle upwelling and less vigorous small-scale convection than would
      have arisen from more localized deformation. This lack of highly focused mantle
      upwelling may explain a deficit of rift-related volcanics in the Rio Grande rift
      compared to other major rift systems such as the Kenya rift.

PMID- 15729339
TI  - Counter-rotating microplates at the Galapagos triple junction.
AB  - An 'incipient' spreading centre east of (and orthogonal to) the East Pacific Rise
      at 2 degrees 40' N has been identified as forming a portion of the northern
      boundary of the Galapagos microplate. This spreading centre was described as a
      slowly diverging, westward propagating rift, tapering towards the East Pacific
      Rise. Here we present evidence that the 'incipient rift' has also rifted towards
      the east and opens anticlockwise about a pivot at its eastern end. The 'incipient
      rift' then bounds a second microplate, north of the clockwise-rotating Galapagos
      microplate. The Galapagos triple junction region, in the eastern equatorial
      Pacific Ocean, thus consists of two counter-rotating microplates partly separated
      by the Hess Deep rift. Our kinematic solution for microplate motion relative to
      the major plates indicates that the two counter-rotating microplates may be
      treated as rigid blocks driven by drag on the microplates' edges3.

PMID- 15729340
TI  - New evidence on deinonychosaurian dinosaurs from the Late Cretaceous of
      Patagonia.
AB  - Most of what is known about the evolution of deinonychosaurs (that is, the group
      of theropods most closely related to birds) is based on discoveries from North
      America and Asia. Except for Unenlagia comahuensis and some fragmentary remains
      from northern Africa, no other evidence was available on deinonychosaurian
      diversity in Gondwana. Here we report a new, Late Cretaceous member of the clade,
      Neuquenraptor argentinus gen. et sp. nov., representing uncontroversial evidence
      of a deinonychosaurian theropod in the Southern Hemisphere. The new discovery
      demonstrates that Cretaceous theropod faunas from the southern continents shared
      greater similarity with those of the northern landmasses than previously thought.
      Available evidence suggests that deinonychosaurians were probably distributed
      worldwide at least by the beginning of the Cretaceous period. The phylogenetic
      position of the new deinonychosaur, as well as other Patagonian coelurosaurian
      theropods, is compatible with a vicariance model of diversification for some
      groups of Gondwanan and Laurasian dinosaurs.

PMID- 15729341
TI  - Prokaryotic cells of the deep sub-seafloor biosphere identified as living
      bacteria.
AB  - Chemical analyses of the pore waters from hundreds of deep ocean sediment cores
      have over decades provided evidence for ongoing processes that require biological
      catalysis by prokaryotes. This sub-seafloor activity of microorganisms may
      influence the surface Earth by changing the chemistry of the ocean and by
      triggering the emission of methane, with consequences for the marine carbon cycle
      and even the global climate. Despite the fact that only about 1% of the total
      marine primary production of organic carbon is available for deep-sea
      microorganisms, sub-seafloor sediments harbour over half of all prokaryotic cells
      on Earth. This estimation has been calculated from numerous microscopic cell
      counts in sediment cores of the Ocean Drilling Program. Because these counts
      cannot differentiate between dead and alive cells, the population size of living
      microorganisms is unknown. Here, using ribosomal RNA as a target for the
      technique known as catalysed reporter deposition-fluorescence in situ
      hybridization (CARD-FISH), we provide direct quantification of live cells as
      defined by the presence of ribosomes. We show that a large fraction of the sub
      seafloor prokaryotes is alive, even in very old (16 million yr) and deep (> 400
      m) sediments. All detectable living cells belong to the Bacteria and have
      turnover times of 0.25-22 yr, comparable to surface sediments.

PMID- 15729342
TI  - The genome of the protist parasite Entamoeba histolytica.
AB  - Entamoeba histolytica is an intestinal parasite and the causative agent of
      amoebiasis, which is a significant source of morbidity and mortality in
      developing countries. Here we present the genome of E. histolytica, which reveals
      a variety of metabolic adaptations shared with two other amitochondrial protist
      pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include
      reduction or elimination of most mitochondrial metabolic pathways and the use of
      oxidative stress enzymes generally associated with anaerobic prokaryotes.
      Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial
      genes into the E. histolytica genome, the effects of which centre on expanding
      aspects of E. histolytica's metabolic repertoire. The presence of these genes and
      the potential for novel metabolic pathways in E. histolytica may allow for the
      development of new chemotherapeutic agents. The genome encodes a large number of
      novel receptor kinases and contains expansions of a variety of gene families,
      including those associated with virulence. Additional genome features include an
      abundance of tandemly repeated transfer-RNA-containing arrays, which may have a
      structural function in the genome. Analysis of the genome provides new insights
      into the workings and genome evolution of a major human pathogen.

PMID- 15729343
TI  - Excitatory cortical neurons form fine-scale functional networks.
AB  - The specificity of cortical neuron connections creates columns of functionally
      similar neurons spanning from the pia to the white matter. Here we investigate
      whether there is an additional, finer level of specificity that creates
      subnetworks of excitatory neurons within functional columns. We tested for fine
      scale specificity of connections to cortical layer 2/3 pyramidal neurons in rat
      visual cortex by using cross-correlation analyses of synaptic currents evoked by
      photostimulation. Recording simultaneously from adjacent layer 2/3 pyramidal
      cells, we find that when they are connected to each other (20% of all recorded
      pairs) they share common input from layer 4 and within layer 2/3. When adjacent
      layer 2/3 neurons are not connected to each other, they share very little (if
      any) common excitatory input from layers 4 and 2/3. In contrast, all layer 2/3
      neurons share common excitatory input from layer 5 and inhibitory input from
      layers 2/3 and 4, regardless of whether they are connected to each other. Thus,
      excitatory connections from layer 4 to layer 2/3 and within layer 2/3 form fine
      scale assemblies of selectively interconnected neurons; inhibitory connections
      and excitatory connections from layer 5 link neurons across these fine-scale
      subnetworks. Relatively independent subnetworks of excitatory neurons are
      therefore embedded within the larger-scale functional architecture; this allows
      neighbouring neurons to convey information more independently than suggested by
      previous descriptions of cortical circuitry.

PMID- 15729344
TI  - Different time courses of learning-related activity in the prefrontal cortex and
      striatum.
AB  - To navigate our complex world, our brains have evolved a sophisticated ability to
      quickly learn arbitrary rules such as 'stop at red'. Studies in monkeys using a
      laboratory test of this capacity--conditional association learning--have revealed
      that frontal lobe structures (including the prefrontal cortex) as well as
      subcortical nuclei of the basal ganglia are involved in such learning. Neural
      correlates of associative learning have been observed in both brain regions, but
      whether or not these regions have unique functions is unclear, as they have
      typically been studied separately using different tasks. Here we show that during
      associative learning in monkeys, neural activity in these areas changes at
      different rates: the striatum (an input structure of the basal ganglia) showed
      rapid, almost bistable, changes compared with a slower trend in the prefrontal
      cortex that was more in accordance with slow improvements in behavioural
      performance. Also, pre-saccadic activity began progressively earlier in the
      striatum but not in the prefrontal cortex as learning took place. These results
      support the hypothesis that rewarded associations are first identified by the
      basal ganglia, the output of which 'trains' slower learning mechanisms in the
      frontal cortex.

PMID- 15729345
TI  - CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding
      domains.
AB  - ABC (ATP-binding cassette) proteins constitute a large family of membrane
      proteins that actively transport a broad range of substrates. Cystic fibrosis
      transmembrane conductance regulator (CFTR), the protein dysfunctional in cystic
      fibrosis, is unique among ABC proteins in that its transmembrane domains comprise
      an ion channel. Opening and closing of the pore have been linked to ATP binding
      and hydrolysis at CFTR's two nucleotide-binding domains, NBD1 and NBD2 (see, for
      example, refs 1, 2). Isolated NBDs of prokaryotic ABC proteins dimerize upon
      binding ATP, and hydrolysis of the ATP causes dimer dissociation. Here, using
      single-channel recording methods on intact CFTR molecules, we directly follow
      opening and closing of the channel gates, and relate these occurrences to ATP
      mediated events in the NBDs. We find that energetic coupling between two CFTR
      residues, expected to lie on opposite sides of its predicted NBD1-NBD2 dimer
      interface, changes in concert with channel gating status. The two monitored side
      chains are independent of each other in closed channels but become coupled as the
      channels open. The results directly link ATP-driven tight dimerization of CFTR's
      cytoplasmic nucleotide-binding domains to opening of the ion channel in the
      transmembrane domains. This establishes a molecular mechanism, involving dynamic
      restructuring of the NBD dimer interface, that is probably common to all members
      of the ABC protein superfamily.

PMID- 15729346
TI  - Pax3 functions at a nodal point in melanocyte stem cell differentiation.
AB  - Most stem cells are not totipotent. Instead, they are partially committed but
      remain undifferentiated. Upon appropriate stimulation they are capable of
      regenerating mature cell types. Little is known about the genetic programmes that
      maintain the undifferentiated phenotype of lineage-restricted stem cells. Here we
      describe the molecular details of a nodal point in adult melanocyte stem cell
      differentiation in which Pax3 simultaneously functions to initiate a melanogenic
      cascade while acting downstream to prevent terminal differentiation. Pax3
      activates expression of Mitf, a transcription factor critical for melanogenesis,
      while at the same time it competes with Mitf for occupancy of an enhancer
      required for expression of dopachrome tautomerase, an enzyme that functions in
      melanin synthesis. Pax3-expressing melanoblasts are thus committed but
      undifferentiated until Pax3-mediated repression is relieved by activated beta
      catenin. Thus, a stem cell transcription factor can both determine cell fate and
      simultaneously maintain an undifferentiated state, leaving a cell poised to
      differentiate in response to external stimuli.

PMID- 15729347
TI  - State transitions and light adaptation require chloroplast thylakoid protein
      kinase STN7.
AB  - Photosynthetic organisms are able to adjust to changing light conditions through
      state transitions, a process that involves the redistribution of light excitation
      energy between photosystem II (PSII) and photosystem I (PSI). Balancing of the
      light absorption capacity of these two photosystems is achieved through the
      reversible association of the major antenna complex (LHCII) between PSII and PSI
      (ref. 3). Excess stimulation of PSII relative to PSI leads to the reduction of
      the plastoquinone pool and the activation of a kinase; the phosphorylation of
      LHCII; and the displacement of LHCII from PSII to PSI (state 2). Oxidation of the
      plastoquinone pool by excess stimulation of PSI reverses this process (state 1).
      The Chlamydomonas thylakoid-associated Ser-Thr kinase Stt7, which is required for
      state transitions, has an orthologue named STN7 in Arabidopsis. Here we show that
      loss of STN7 blocks state transitions and LHCII phosphorylation. In stn7 mutant
      plants the plastoquinone pool is more reduced and growth is impaired under
      changing light conditions, indicating that STN7, and probably state transitions,
      have an important role in response to environmental changes.

PMID- 15729349
TI  - Job movements.

PMID- 15729350
TI  - India in demand.

PMID- 15729348
TI  - Functional cartography of complex metabolic networks.
AB  - High-throughput techniques are leading to an explosive growth in the size of
      biological databases and creating the opportunity to revolutionize our
      understanding of life and disease. Interpretation of these data remains, however,
      a major scientific challenge. Here, we propose a methodology that enables us to
      extract and display information contained in complex networks. Specifically, we
      demonstrate that we can find functional modules in complex networks, and classify
      nodes into universal roles according to their pattern of intra- and inter-module
      connections. The method thus yields a 'cartographic representation' of complex
      networks. Metabolic networks are among the most challenging biological networks
      and, arguably, the ones with most potential for immediate applicability. We use
      our method to analyse the metabolic networks of twelve organisms from three
      different superkingdoms. We find that, typically, 80% of the nodes are only
      connected to other nodes within their respective modules, and that nodes with
      different roles are affected by different evolutionary constraints and pressures.
      Remarkably, we find that metabolites that participate in only a few reactions but
      that connect different modules are more conserved than hubs whose links are
      mostly within a single module.

PMID- 15729352
TI  - Scientists and societies. Horizons in molecular biology.

PMID- 15729355
TI  - Development of a regional flow cytometry center for diagnosis of childhood
      leukemia in Central America.

PMID- 15729356
TI  - Listeria monocytogenes exploits ERM protein functions to efficiently spread from
      cell to cell.
AB  - Cell-to-cell spread is a fundamental step in the infection cycle of Listeria
      monocytogenes that strictly depends on the formation of bacteria-induced
      protrusions. Since Listeria actin tails in the protrusions are tightly associated
      with the plasma membrane, we hypothesised that membrane-cytoskeleton linkers
      would be required for initiating and sustaining their formation and the
      subsequent cell-to-cell spread. We have found that ezrin, a member of the ezrin,
      radixin and moesin (ERM) family that functions as a key membrane-cytoskeleton
      linker, accumulates at Listeria protrusions. The ability of Listeria to induce
      protrusions and effectively spread between adjacent cells depends on the
      interaction of ERM proteins with both a membrane component such as CD44 and actin
      filaments. Interfering with either of these interactions or with ERM proteins
      phosphorylation not only reduces the number of protrusions but also alters their
      morphology, resulting in the formation of short and collapsed protrusions. As a
      consequence, Listeria cell-to-cell spread is severely impaired. Thus, ERM
      proteins are exploited by Listeria to escape the host immune response and to
      succeed in the development of the infection.

PMID- 15729357
TI  - Dectin-1 mediates macrophage recognition of Candida albicans yeast but not
      filaments.
AB  - The ability of Candida albicans to rapidly and reversibly switch between yeast
      and filamentous morphologies is crucial to pathogenicity, and it is thought that
      the filamentous morphology provides some advantage during interaction with the
      mammalian immune system. Dectin-1 is a receptor that binds beta-glucans and is
      important for macrophage phagocytosis of fungi. The receptor also collaborates
      with Toll-like receptors for inflammatory activation of phagocytes by fungi. We
      show that yeast cell wall beta-glucan is largely shielded from Dectin-1 by outer
      wall components. However, the normal mechanisms of yeast budding and cell
      separation create permanent scars which expose sufficient beta-glucan to trigger
      antimicrobial responses through Dectin-1, including phagocytosis and activation
      of reactive oxygen production. During filamentous growth, no cell separation or
      subsequent beta-glucan exposure occurs, and the pathogen fails to activate Dectin
      1. The data demonstrate a mechanism by which C. albicans shape alone directly
      contributes to the method by which phagocytes recognize the fungus.

PMID- 15729359
TI  - The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase.
AB  - Netrin-1 receptors UNC5H (UNC5H1-4) were originally proposed to mediate the
      chemorepulsive activity of netrin-1 during axonal guidance processes. However,
      UNC5H receptors were more recently described as dependence receptors and, as
      such, able to trigger apoptosis in the absence of netrin-1. They were also
      proposed as putative tumor suppressors. Here, we show that UNC5H2 physically
      interacts with the serine/threonine kinase death-associated protein kinase (DAP
      kinase) both in cell culture and in embryonic mouse brains. This interaction
      occurs in part through the respective death domains of UNC5H2 and DAP-kinase.
      Moreover, part of UNC5H2 proapoptotic activity occurs through this interaction
      because UNC5H2-induced cell death is partly impaired in the presence of dominant
      negative mutants of DAP-kinase or in DAP-kinase mutant murine embryonic
      fibroblast cells. In the absence of netrin-1, UNC5H2 reduces DAP-kinase
      autophosphorylation on Ser308 and increases the catalytic activity of the kinase
      while netrin-1 blocks UNC5H2-dependent DAP-kinase activation. Thus, the pair
      netrin-1/UNC5H2 may regulate cell fate by controlling the proapoptotic kinase
      activity of DAP-kinase.

PMID- 15729358
TI  - Targeting fusion protein/corepressor contact restores differentiation response in
      leukemia cells.
AB  - The AML1/ETO and PML/RARalpha leukemia fusion proteins induce acute myeloid
      leukemia by acting as transcriptional repressors. They interact with
      corepressors, such as N-CoR and SMRT, that recruit a multiprotein complex
      containing histone deacetylases on crucial myeloid differentiation genes. This
      leads to gene repression contributing to generate a differentiation block. We
      expressed in leukemia cells containing PML/RARalpha and AML1/ETO N-CoR protein
      fragments derived from fusion protein/corepressor interaction surfaces. This
      blocks N-CoR/SMRT binding by these fusion proteins, and disrupts the repressor
      protein complex. In consequence, the expression of genes repressed by these
      fusion proteins increases and differentiation response to vitamin D3 and retinoic
      acid is restored in previously resistant cells. The alteration of PML/RARalpha-N
      CoR/SMRT connections triggers proteasomal degradation of the fusion protein. The
      N-CoR fragments are biologically effective also when directly transduced by
      virtue of a protein transduction domain. Our data indicate that fusion protein
      activity is permanently required to maintain the leukemia phenotype and show the
      route to developing a novel therapeutic approach for leukemia, based on its
      molecular pathogenesis.

PMID- 15729360
TI  - p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating
      its interaction with GKAP.
AB  - Activation of the p38 MAP kinase pathways is crucial for the adaptation of
      mammalian cells to changes in the osmolarity of the environment. Here we identify
      SAP97/hDlg, the mammalian homologue of the Drosophila tumour suppressor Dlg, as a
      physiological substrate for the p38gamma MAP kinase (SAPK3/p38gamma) isoform.
      SAP97/hDlg is a scaffold protein that forms multiprotein complexes with a variety
      of proteins and is targeted to the cytoskeleton by its association with the
      protein guanylate kinase-associated protein (GKAP). The SAPK3/p38gamma-catalysed
      phosphorylation of SAP97/hDlg triggers its dissociation from GKAP and therefore
      releases it from the cytoskeleton. This is likely to regulate the integrity of
      intercellular-junctional complexes, and cell shape and volume in response to
      osmotic stress.

PMID- 15729361
TI  - Integrase inhibitors to treat HIV/AIDS.
AB  - HIV integrase is a rational target for treating HIV infection and preventing
      AIDS. It took approximately 12 years to develop clinically usable inhibitors of
      integrase, and Phase I clinical trials of integrase inhibitors have just begun.
      This review focuses on the molecular basis and rationale for developing integrase
      inhibitors. The main classes of lead compounds are also described, as well as the
      concept of interfacial inhibitors of protein-nucleic-acid interactions that might
      apply to the clinically used strand-transfer inhibitors.

PMID- 15729362
TI  - The evolving role of natural products in drug discovery.
AB  - Natural products and their derivatives have historically been invaluable as a
      source of therapeutic agents. However, in the past decade, research into natural
      products in the pharmaceutical industry has declined, owing to issues such as the
      lack of compatibility of traditional natural-product extract libraries with high
      throughput screening. However, as discussed in this review, recent technological
      advances that help to address these issues, coupled with unrealized expectations
      from current lead-generation strategies, have led to a renewed interest in
      natural products in drug discovery.

PMID- 15729363
TI  - Haplotype analysis of the preprotachykinin-1 (TAC1) gene in multiple sclerosis.
AB  - The potential relevance of chromosome 7q21-22 in susceptibility to multiple
      sclerosis (MS) has been highlighted in genome-wide linkage screens as well as in
      association studies of 7q-specific polymorphic microsatellites. Especially,
      recent, independently performed studies have provided evidence for significant
      association of the markers D7S554 and D7S3126 with MS in Sardinian, Northern
      Irish and Spanish-American cohorts. The gene most closely located to these
      markers is the neuropeptide preprotachykinin-1 (TAC1) gene. Both its position and
      the array of biological functions exerted by its expression products make it a
      logical primary choice for further scrutiny as the putative chromosome 7q21-22 MS
      susceptibility gene. We report identification of eight polymorphisms in this gene
      by means of a sequencing approach. A Northern Irish case-control was typed for
      six of these polymorphisms. One of these, an intron 1 single-nucleotide
      polymorphism (SNP), showed significant association with MS (P=0.009). Two-marker
      haplotypes composed of allelic combinations of TAC1 promoter-intron 1 SNPs were
      highly significantly associated with MS and more so with the relapsing-remitting
      form of this disease. While independent reproduction of these data in other data
      sets is indicated, our work is suggestive for a role of the TAC1 gene in MS.
      Genes and Immunity (2005) 6, 265-270. doi:10.1038/sj.gene.6364175 Published
      online 24 February 2005.

PMID- 15729364
TI  - Functional variants in SUMO4, TAB2, and NFkappaB and the risk of type 1 diabetes.
AB  - Several functional genetic variants that can potentially modulate the activity of
      NFkappaB have been recently described. As reduced NFkappaB activity has been
      implicated in risk for autoimmune diabetes in the NOD mouse, these variants were
      tested for allelic association with type 1 diabetes (T1D) in a family based
      study. Alleles at markers in the TAB2/SUMO4 locus on chromosome 6q had been
      previously reported to be associated with T1D in two separate studies, but these
      studies disagreed on the identity of the risk allele. The current study failed to
      confirm either of these results. No significant evidence of association with T1D
      was obtained for three SNP markers in the TAB2/SUMO4 region. An additional
      functional variant in the promoter of the NFKB1 gene that has been shown to
      directly affect the expression of NFkappaB was also tested.

PMID- 15729365
TI  - Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated
      with cirrhosis in chronic HCV-1 infection.
AB  - Immune response to viral infection is an important determinant of liver injury in
      chronic hepatitis C (CHC). Experimental and clinical data suggest a protective
      role of interleukin-10 (IL-10) in hepatic fibrogenesis. The significance of two
      SNPs of the interleukin-10 receptor 1 (IL-10R1), S138G (SNP3) and G330R (SNP4)
      was investigated on (i) susceptibility to CHC, (ii) progression of hepatic
      fibrosis and (iii) response to interferon/ribavirin therapy. DNA and liver
      biopsies were obtained from 212 patients with HCV (hepatitis C virus)-genotype-1
      infection. The allele frequencies were 0.17 for SNP3 and 0.33 for SNP4, both of
      which were indifferent from healthy controls (0.17 and 0.32, respectively). Stage
      1 liver fibrosis was found in 22 cases (10.4%), stage 2 in 108 (50.9%), stage 3
      in 27 (12.8%), and stage 4 (cirrhosis) in 55 (25.9%). An association was found
      between the SNP4 allele and the presence of cirrhosis (P=0.01). Homozygous SNP4
      individual variants segregated within the cirrhosis group (P=0.03). We found
      neither an association with SNP3 nor with the necroinflammatory disease activity
      (as measured by ALT levels) nor with the response to antiviral therapy. Our work
      implies that IL-10R1 SNP4 is a recessively inherited risk factor for hepatic
      cirrhosis in HCV genotype-1 infection.

PMID- 15729367
TI  - Gene-directed enzyme prodrug therapy with carboxylesterase enhances the
      anticancer efficacy of the conditionally replicating adenovirus AdDelta24.
AB  - Conditionally replicating adenoviruses (CRAds) selectively replicate in and
      thereby kill cancer cells. The CRAd AdDelta24 with pRb-binding-deficient E1A
      kills cancer cells efficiently. Arming CRAds with genes encoding prodrug
      converting enzymes could allow for enhanced anticancer efficacy by the combined
      effects of oncolytic replication and local prodrug activation. Here, we
      investigated combination treatment of human colon cancer cell lines with
      AdDelta24-type CRAds and gene-directed enzyme prodrug therapy (GDEPT) using two
      different enzyme/prodrug systems, that is, thymidine kinase/ganciclovir (TK/GCV)
      and carboxylesterase (CE)/CPT-11. On all three cell lines tested, GDEPT with
      TK/GCV made CRAd treatment less efficacious. In contrast, expression of a
      secreted form of CE (sCE2) combined with CPT-11 treatment markedly enhanced the
      efficacy of AdDelta24 virotherapy. Based on this observation, we constructed an
      AdDelta24 variant expressing sCE2. In the absence of CPT-11, this new CRAd Ad5
      Delta24.E3-sCE2 was similarly effective as its parent in killing human colon
      cancer cells. Low concentrations of CPT-11 inhibited Ad5-Delta24.E3-sCE2
      propagation. Nevertheless, CPT-11 specifically augmented the cytotoxicity of Ad5
      Delta24.E3-sCE2 against all three-colon cancer cell lines. Hence, the positive
      contribution of sCE2/CPT-11 GDEPT to colon cancer cytotoxicity outweighed its
      negative influence on CRAd propagation. Therefore, CRAd-sCE2/CPT-11 combination
      therapy appears useful for more effective treatment of colon cancer.

PMID- 15729368
TI  - VP22-mediated intercellular transport for suicide gene therapy under oxic and
      hypoxic conditions.
AB  - During herpes simplex virus type 1 (HSV 1) infection, the tegument protein VP22
      is exported from infected cells to the nuclei of surrounding uninfected cells.
      These intercellular transport characteristics have prompted the exploitation of
      VP22 fusion proteins for cancer gene therapy, with the goal of maximizing the
      bystander effect. Since solid tumors contain hypoxic cell populations that are
      often refractive to therapy, for efficient targeting, it would be optimal if VP22
      functioned even at reduced oxygen concentrations. In the present work, VP22
      activity under hypoxic conditions was examined for the first time. Plasmid
      transfected human glioma U87-MG and U373-MG cells expressing VP22 fused to the
      green fluorescent protein (GFP) showed protein export to untransfected cells
      under tumor oxygenation conditions (0-5% O(2)). For suicide gene therapy, VP22
      activity was demonstrated under hypoxia by coupling VP22 to the HSV thymidine
      kinase (HSVtk). In the presence of the prodrug ganciclovir, cell cultures
      expressing VP22-HSVtk showed a significant increase in toxicity compared with
      cells transfected with a construct containing HSVtk only, under all tested
      conditions. To allow effective suicide gene therapy and simultaneous
      visualization of therapeutic enzyme localization, a triple fusion protein GFP
      HSVtk-VP22 was engineered. Functionality of all components was demonstrated under
      oxia and hypoxia.

PMID- 15729370
TI  - Beta defensin-3 engineered epidermis shows highly protective effect for bacterial
      infection.
AB  - Defensins are small cationic proteins that harbor broad-spectrum microbicidal
      activity against bacteria, fungi and viruses. This study examines the effects on
      pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to
      combat bacterial infections. First, we examined the localization of HBD3 in the
      epidermis and observed HBD3 in the intercellular spaces and lamellar bodies of
      the upper epidermal layers. This result showed HBD3 expressed and assembled in
      the outer layers of the epidermis was suspected to counter the invading
      microorganisms. Next, we established a keratinocyte cell line that stably
      expressed HBD3 and found that the culture medium showed antibacterial activity.
      Furthermore, we prepared an epidermal sheet of these cells with the HBD3 gene and
      grafted this onto a dermal wound on a nude rat. The HBD3 engineered epidermis
      demonstrated significant antimicrobial activity. Skin ulcers without epidermis
      are constantly exposed to invading microorganisms. Biopsy samples of re
      epithelizing epidermis from patients with skin ulcers were collected, and HBD3
      mRNA level measured in the epidermis. The epidermal samples from the ulcer skin
      expressed 2.5 times higher levels of HBD3 transcript than those in the control
      skin. These results, taken together, indicate that the therapeutic introduction
      of the HBD3 gene into somatic cells may provide a new gene therapy strategy for
      intractable infectious diseases.

PMID- 15729369
TI  - Exploring RNA interference as a therapeutic strategy for renal disease.
AB  - The short synthetic interfering RNA duplexes (siRNAs) can selectively suppress
      gene expression in somatic mammalian cells without nonselective toxic effects of
      double-stranded RNA (dsRNA). However, a selective in vivo delivery of siRNA
      transfer has not been reported in kidney. Here, we investigated whether injection
      of synthetic siRNAs via renal artery followed by electroporation could be
      effective and therapeutic in silencing specific gene in glomerulus. We
      investigated the effect of siRNA in rat cultured mesangial cells (MCs) and showed
      that siRNA sequence-specific suppression of transgene expression was over a 1000
      fold more potent than that by antisense oligodeoxynucleotide (ASODN).
      Transfection of siRNA targeting luciferase into rat kidneys significantly
      inhibited expression of a cotransfected luciferase expression vector in vivo. The
      delivery of siRNA targeting enhanced green fluorescent protein (EGFP) in the
      transgenic 'green' rat reduced endogenous EGFP expression, mainly in glomerular
      MCs. Furthermore, RNAi targeting against TGF-beta1 significantly suppressed TGF
      beta1 mRNA and protein expression, thereby ameliorated the progression of matrix
      expansion in experimental glomerulonephritis. In addition, vector-based RNAi also
      inhibited TGF-beta1 expression in vitro and in vivo. In conclusion, siRNA
      directed TGF-beta1 silencing may be of therapeutic value in the prevention and
      treatment of fibrotic diseases.

PMID- 15729371
TI  - Enhanced antimetastatic effect of fetal liver kinase 1 extracellular domain and
      interferon-gamma fusion gene-modified dendritic cell vaccination.
AB  - Antiangiogenic immunotherapy benefits from targeting antigens expressed on
      genetically stable endothelial cells and represents a novel modality for cancer
      treatment. Vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2, also
      known as flk1 in mouse) mediated VEGF signaling is the key rate-limiting step in
      angiogenesis. Blockade of the flk1 signaling pathway can significantly inhibit
      tumor cell-induced angiogenesis and lead to inhibition of tumor metastasis.
      Interferon-gamma (IFN-gamma) is a pleiotropic cytokine, which plays an important
      role in cell-mediated immunity. In this study, we tested the hypothesis that
      immunization of mice with soluble flk1 (sflk1) and IFN-gamma fusion gene
      transfected dendritic cells (DC-sflk1-IFN-gamma) would induce a potent CTL
      response to flk1, leading to an inhibition of tumor-induced angiogenesis and
      metastasis. Our data show that immunization of mice with sflk1 gene-modified DC
      (DC-sflk1) could induce a CTL response to flk1, leading to profound inhibition of
      tumor-cell-induced angiogenesis and metastasis. However, more striking
      antimetastatic effects were achieved through induction of enhanced CTL response
      to flk1 and augmented inhibition of angiogenesis when mice were immunized with DC
      sflk1-IFN-gamma. In vivo T-cell subset depletion experiments showed that CD8(+) T
      cells were mainly responsible for this antimetastatic effect. Our data extend the
      notion that DC-based active antiangiogenic immunotherapy is an effective modality
      for cancer treatment, and show that the antitumor efficacy of this strategy can
      be improved by combination with DC-based cytokine immunotherapy.

PMID- 15729373
TI  - Circulating endothelial progenitor cells in subjects with erectile dysfunction.
AB  - Erectile dysfunction (ED) is often the first clinical sign of endothelial
      dysfunction and may precede overt cardiovascular diseases. Bone marrow-derived
      endothelial progenitor cells migrate into the peripheral circulation to promote
      endothelial repair. The number of circulating progenitor cells is reduced in
      patients with cardiovascular risk factor. The objective of our study was to
      determine the number of these cells in patients with ED both with and without
      cardiovascular risk factors. These subjects have lower number of circulating
      progenitor cells, confirming the existence of an endothelial dysfunction and
      supplying the evidence that ED may be the first symptom of an endothelial damage.

PMID- 15729372
TI  - Hydrodynamic liver gene transfer mechanism involves transient sinusoidal blood
      stasis and massive hepatocyte endocytic vesicles.
AB  - The present study contributes to clarify the mechanism underlying the high
      efficacy of hepatocyte gene transfer mediated by hydrodynamic injection. Gene
      transfer experiments were performed employing the hAAT gene, and the efficacy and
      differential identification in mouse plasma of human transgene versus mouse gene
      was assessed by ELISA and proteomic procedures, respectively. By applying
      different experimental strategies such as cumulative dose-response efficacy,
      hemodynamic changes reflected by venous pressures, intravital microscopy, and
      morphological changes established by transmission electron microscopy, we found
      that: (a) cumulative multiple doses of transgene by hydrodynamic injection are
      efficient and well tolerated, resulting in therapeutic plasma levels of hAAT; (b)
      hydrodynamic injection mediates a transient inversion of intrahepatic blood flow,
      with circulatory stasis for a few minutes mainly in pericentral vein sinusoids;
      (c) transmission electron microscopy shows hydrodynamic injection to promote
      massive megafluid endocytic vesicles among hepatocytes around the central vein
      but not in hepatocytes around the periportal vein. We suggest that the mechanism
      of hydrodynamic liver gene transfer involves transient inversion of intrahepatic
      flow, sinusoidal blood stasis, and massive fluid endocytic vesicles in
      pericentral vein hepatocytes.

PMID- 15729374
TI  - Erectile dysfunction in patients with coronary artery disease.
AB  - Recent studies suggest that erectile dysfunction (ED) may be an early marker of
      endothelial dysfunction and coronary artery disease (CAD). Conversely, patients
      with CAD commonly have ED. The phosphodiesterase 5 (PDE5) inhibitors are very
      effective for the treatment of ED in patients with CAD. Numerous studies show
      that this class of drugs is in general safe in patients with stable CAD and these
      agents do not exacerbate ischemia in men with CAD undergoing exercise stress
      testing. Analysis of placebo-controlled trials did not show an increase in
      cardiovascular events among men receiving PDE5 inhibitors, and post-marketing
      surveillance studies with sildenafil did not observe an increase in
      cardiovascular events compared to expected age-matched rates. Organic nitrates
      remain a contraindication for PDE5 inhibitors and alpha blockers have
      precautions/contraindications depending upon specific drugs. The Princeton
      Consensus Guidelines (soon to be updated) suggest a logical approach to the
      patient with CAD seeking therapy for sexual dysfunction.

PMID- 15729376
TI  - Age-related factors that confound peripheral pulse timing characteristics in
      Caucasian children.
AB  - Characteristics obtained from peripheral pulses can be used to assess the status
      of cardiovascular system of subjects. However, nonintrusive techniques are
      preferred when prolonged monitoring is required for their comfort. Pulse transit
      time (PTT) measurement has showed its potentials to monitor timing changes in
      peripheral pulse in cardiovascular and respiratory studies. In children, the
      common peripheries used for these studies are fingers or toes. Presently, there
      is no known study conducted on children to investigate the possible physiologic
      parameters that can confound PTT measure at these sites. In this study, PTT
      values from both peripheral sites were recorded from 55 healthy Caucasian
      children (39 male) with mean age of 8.4+/-2.3 years (range 5-12 years).
      Peripheries' path length, heart rate, systolic blood pressure, diastolic blood
      pressure (DBP) and mean arterial pressure (MAP) were measured to investigate
      their contributions to PTT measurement. The results reveal that PTT is
      significantly related to all parameters (P<0.05), except for DBP and MAP. Age is
      observed to be the dominant factor that affects PTT at both peripheries in a
      child. Regression equations for PTT were derived for measuring from a finger and
      toe, (6.09 age+189.2) ms and (6.70 age+243.0) ms, respectively.

PMID- 15729375
TI  - Regulation of energy balance and blood pressure: are genetic polymorphisms
      pertinent?

PMID- 15729377
TI  - Pulse pressure and peripheral arterial vasoreactivity.

PMID- 15729378
TI  - Brachial-ankle pulse wave velocity: an index of central arterial stiffness?
AB  - Brachial-ankle pulse wave velocity (baPWV) is a promising technique to assess
      arterial stiffness conveniently. However, it is not known whether baPWV is
      associated with well-established indices of central arterial stiffness. We
      determined the relation of baPWV with aortic (carotid-femoral) PWV, leg (femoral
      ankle) PWV, and carotid augmentation index (AI) by using both cross-sectional and
      interventional approaches. First, we studied 409 healthy adults aged 18-76 years.
      baPWV correlated significantly with aortic PWV (r = 0.76), leg PWV (r = 0.76),
      and carotid AI (r = 0.52). A stepwise regression analysis revealed that aortic
      PWV was the primary independent correlate of baPWV, explaining 58% of the total
      variance in baPWV. Additional 23% of the variance was explained by leg PWV.
      Second, 13 sedentary healthy men were studied before and after a 16-week moderate
      aerobic exercise intervention (brisk walking to jogging; 30-45 min/day; 4-5
      days/week). Reductions in aortic PWV observed with the exercise intervention were
      significantly and positively associated with the corresponding changes in baPWV
      (r = 0.74). A stepwise regression analysis revealed that changes in aortic PWV
      were the only independent correlate of changes in baPWV (beta = 0.74), explaining
      55% of the total variance. These results suggest that baPWV may provide
      qualitatively similar information to those derived from central arterial
      stiffness although some portions of baPWV may be determined by peripheral
      arterial stiffness.

PMID- 15729379
TI  - Effects of weight status on the recommendations of and adherence to lifestyle
      modifications among hypertensive adults.
AB  - Overweight and obese hypertensive patients can greatly benefit from high
      adherence rates for lifestyle modifications. The objectives of this paper were to
      investigate how patients' weight status affected physicians' recommendations of
      lifestyle modifications and patients' adherence after they received the
      recommendations. The patients were adults (18+ years of age) with hypertension
      (prehypertension, Stage I and Stage II hypertension). The National Health and
      Nutrition Examination Survey (NHANES) 1999-2000 was used. Weight status was
      categorized as normal/underweight, overweight and obese. Physicians'
      recommendations of and patients' adherence to lifestyle modifications (weight
      control, exercise, sodium intake reduction, alcohol intake reduction) were
      examined using descriptive and multivariate analyses, controlling for weight
      status, hypertension stage, comorbidities and demographic characteristics. About
      57.0% of the US adult population in 1999-2000 had prehypertension, Stages I or II
      hypertension. Among the hypertensive adults, 30.3% were normal/underweight, 32.6%
      were overweight and 37.2% were obese. We found that physicians were more
      aggressive in recommending lifestyle modification for obese patients. In
      contrast, obese hypertensive patients were not found to be more likely than
      normal/underweight patients to adhere to lifestyle modification recommendations.
      In addition, adherence rates for sodium and alcohol consumption reduction were
      higher than that for either exercise or weight control. In conclusion, more
      aggressive approaches should be taken by physicians to educate obese patients
      about the benefits of lifestyle modifications and to improve adherence to enhance
      the effects of antihypertensive medications.

PMID- 15729380
TI  - Parents of Infants and Children with Kernicterus.

PMID- 15729381
TI  - Full donor chimerism by day 30 after allogeneic peripheral blood progenitor cell
      transplantation is associated with a low risk of relapse in pediatric patients
      with hematological malignancies.

PMID- 15729382
TI  - Risk factors for invasive aspergillosis in neutropenic patients with hematologic
      malignancies.
AB  - Risk factors for invasive aspergillosis (IA) are incompletely identified and may
      undergo changes due to differences in medical practice. A cohort of 189
      consecutive, adult patients with neutropenia hospitalized in the hemato-oncology
      ward of the University hospital Berne between 1995 and 1999 were included in a
      retrospective study to assess risk factors for IA. In total, 45 IA cases (nine
      proven, three probable, 33 possible), 11 patients with refractory fever and 133
      controls were analyzed. IA cases had more often acute leukemia or myelodysplastic
      syndrome (MDS) (88 vs 38%, P < 0.001) and a longer duration of neutropenia (mean
      20.6 vs 9.9 days, P < 0.001). They also had fewer neutropenic episodes during the
      preceding 6 months (mean 0.42 vs 1.03, P < 0.001), that is, confirmed (82%) and
      probable (73%) IA occurred most often during the induction cycle. A short time
      interval ( < or = 14 days) between neutropenic episodes increased the risk of IA
      four-fold (P = 0.06). Bacteremia, however, was not related to the number of
      preceding neutropenic episodes. Therefore, neutropenic patients with leukemia or
      MDS have the highest risk of IA. The risk is highest during the first induction
      cycle of treatment and increases with short-time intervals between treatment
      cycles.

PMID- 15729383
TI  - Signal transduction and cellular functions of the TEL/ARG oncoprotein.
AB  - The TEL/ARG oncogene is formed by t(1;12)(q25;p13) reciprocal translocation and
      is associated with human leukemia. We have previously demonstrated that the
      expression of TEL/ARG in Ba/F3 cells results in prolonged viability and hyper
      responsiveness to IL-3. To determine the molecular mechanisms, a series of
      mutants of TEL/ARG were generated, and each cDNA was expressed in Ba/F3 or CHO
      cells. The PNT domain in TEL and K317 in ARG were essential for both signaling
      and biological effects. The SH3 domain in ARG was required for hyper
      responsiveness to IL-3, but not for prolonged viability. The opposite was true
      for the SH2 domain in ARG. Mutation of Y314 in TEL, a putative GRB2-binding site,
      led to reduced viability, and loss of hyper-responsiveness to IL-3. All
      biological functions were profoundly impaired with deletion of the C-terminus in
      ARG, despite maintaining high levels of its kinase activity. When expressed in
      CHO cells, wild-type TEL/ARG induced the formation of fillopodia, in a fashion
      dependent on the C-terminal portion and intact kinase activity. Thus, these
      results suggest several critical domains within TEL/ARG necessary for function,
      and indicate that the signaling pathways necessary for viability, growth factor
      hyper-responsiveness and cytoskeletal reorganization are likely to be separate.

PMID- 15729384
TI  - Role of USF1 in the differential expression of the human deoxycytidine kinase
      gene in acute myeloid leukemia.

PMID- 15729385
TI  - An acquired G-CSF receptor mutation results in increased proliferation of CMML
      cells from a patient with severe congenital neutropenia.
AB  - Severe congenital neutropenia (CN) is characterized by a maturation arrest of
      myelopoiesis at the promyelocyte stage. Treatment with pharmacological doses of
      recombinant human granulocyte colony-stimulating factor (rh-G-CSF) stimulates
      neutrophil production and decreases the risk of major infectious complications.
      However, approximately 15% of CN patients develop myeloid malignancies that have
      been associated with somatic mutations in the G-CSF receptor (G-CSFR) and RAS
      genes as well as with acquired monosomy 7. We report a CN patient with chronic
      myelomonocytic leukemia (CMML) who never received rh-G-CSF. Molecular analysis
      demonstrated a somatic G-CSFR mutation (C2390T), which led to expression of a
      truncated G-CSFR protein in the CMML. Normal G-CSFR expression was unexpectedly
      absent in primary and cultured CMML. In addition, CMML cells showed monosomy 7
      and an oncogenic NRAS mutation. In vitro culture revealed a G-CSF-dependent
      proliferation of CMML cells, which subsequently differentiated along the
      monocytic/macrophage lineage. Our results provide direct evidence for the in vivo
      expression of a truncated G-CSFR in leukemic cells, which emerged in the absence
      of rh-G-CSF treatment and transduces proliferative signals.

PMID- 15729391
TI  - Taxonomic relationships among Arachis sect. Arachis species as revealed by AFLP
      markers.
AB  - Cultivated peanut, Arachis hypogaea L., is a tetraploid (2n = 4x = 40) species
      thought to be of allopolyploid origin. Its closest relatives are the diploid (2n
      = 2x = 20) annual and perennial species included with it in Arachis sect.
      Arachis. Species in section Arachis represent an important source of novel
      alleles for improvement of cultivated peanut. A better understanding of the level
      of speciation and taxonomic relationships between taxa within section Arachis is
      a prerequisite to the effective use of this secondary gene pool in peanut
      breeding programs. The AFLP technique was used to determine intra- and
      interspecific relationships among and within 108 accessions of 26 species of this
      section. A total of 1328 fragments were generated with 8 primer combinations.
      From those, 239 bands ranging in size from 65 to 760 bp were scored as binary
      data. Genetic distances among accessions ranged from 0 to 0.50. Average distances
      among diploid species (0.30) were much higher than that detected between
      tetraploid species (0.05). Cluster analysis using different methods and principal
      component analysis were performed. The resulting grouping of accessions and
      species supports previous taxonomic classifications and genome designations.
      Based on genetic distances and cluster analysis, A-genome accessions KG 30029
      (Arachis helodes) and KSSc 36009 (Arachis simpsonii) and B-genome accession
      KGBSPSc 30076 (A. ipaensis) were the most closely related to both Arachis
      hypogaea and Arachis monticola. This finding suggests their involvement in the
      evolution of the tetraploid peanut species.

PMID- 15729392
TI  - Survey of a cDNA library from the turkey (Meleagris gallopavo).
AB  - Genome characterization and analysis is an imperative step in identifying and
      selectively breeding for improved traits of agriculturally important species.
      Expressed sequence tags (ESTs) represent a transcribed portion of the genome and
      are an effective way to identify genes within a species. Downstream applications
      of EST projects include DNA microarray construction and interspecies comparisons.
      In this study, 694 ESTs were sequenced and analyzed from a library derived from a
      24-day-old turkey embryo. The 437 unique sequences identified were divided into
      76 assembled contigs and 361 singletons. The majority of significant comparative
      matches occurred between the turkey sequences and sequences reported from the
      chicken. Whole genome sequence from the chicken was used to identify potential
      exon-intron boundaries for selected turkey clones and intron-amplifying primers
      were developed for sequence analysis and single nucleotide polymorphism (SNP)
      discovery. Identified SNPs were genotyped for linkage analysis on two turkey
      reference populations. This study significantly increases the number of EST
      sequences available for the turkey.

PMID- 15729393
TI  - Genomic organization and evolution of the 5S ribosomal DNA in the ancient fish
      sturgeon.
AB  - Ribosomal DNA in sturgeon is informative when analyzed at the molecular level
      because it bears unique characteristics that are, to a certain extent, ancestral
      within vertebrates. In this paper, we examine the structure and the molecular
      evolution of the 5S ribosomal DNA (rDNA) region in 13 sturgeon species, comparing
      both the 5S ribosomal RNA (rRNA) genes and the non-transcribed spacer (NTS)
      sequences between the coding regions. We have found that different NTS and 5S
      gene variants are intermixed in the 5S rDNA arrays of the different sturgeon
      species and that all variants are ancestral, having been maintained over many
      millions of years. Using predictive models, we have found similar levels of
      sequence diversity in the coding regions, as well as in the non-coding region,
      but fixed interspecific differences are underrepresented for 5S genes. However,
      contrary to the expectations, we have not found fixed differences between NTS
      sequences when comparing many pairs of species. Specifically, when they belong to
      the same phylogeographic clade of the four into which the sturgeon is divided,
      but fixation of mutations and divergence is found between species belonging to
      different phylogeographic clades. Our results suggest that the evolution of the
      two parts of the 5S rDNA region cannot be explained exclusively as the outcome of
      a balance between mutational, homogenizing (i.e., gene conversion as a
      predominant force in sturgeon), and selective forces. Rather, they suggest that
      other factors (i.e., hybridization) might be superimposed over those forces and
      thus could to some extent be masking their effects.

PMID- 15729394
TI  - Induction of wheat defense and stress-related genes in response to Fusarium
      graminearum.
AB  - Fusarium head blight (FHB), caused by species of the fungus Fusarium, is a
      worldwide disease of wheat (Triticum aestivum L.). The Chinese T. aestivum
      'Ning7840' is one of few wheat cultivars with resistance to FHB. To identify
      differentially expressed genes corresponding to FHB resistance, a cDNA library
      was constructed using pooled mRNA isolated from glumes of 'Ning7840' harvested at
      2, 6, 12, 24, 36, 72, and 96 h after inoculation (hai) with a conidia spore
      suspension of Fusarium graminearum. Suppressive subtractive hybridization (SSH)
      cDNA subtraction was carried out using pooled glume mRNAs from the tester and the
      control. The cDNA library was differentially screened using the forward
      subtracted cDNAs and the reverse subtracted cDNAs as probes. Twenty-four clones
      with significant matches to either plant (16 sequences) or fungal (8 sequences)
      genes were isolated based on their specific hybridization with forward subtracted
      cDNA and not reverse subtracted cDNA. Six putative defense-related genes were
      confirmed by real-time quantitative reverse-transcriptase PCR. Many-fold higher
      induction of three clones (A3F8, B10H1, and B11H3) in the resistant genotypes
      compared with susceptible genotypes indicates a putative role in the resistance
      response to Fusarium graminearum. Transcript accumulations of P450, chitinase
      (Chi1), and one unknown gene (clone B8Q9) in both resistant and susceptible
      genotypes suggest an involvement in a generalized resistance response to F.
      graminearum. Nucleotide sequence analysis showed that cDNA clone A4C6 encodes a
      cytochrome P450 gene (CYP709C3v2), including 14 N-terminal amino acids that have
      a membrane-associated helical motif. Other domains characteristic of eukaryotic
      P450 are also present in CYP709C3v2. The deduced polypeptide of cDNA clone B2H2
      encodes an acidic isoform of class I chitinase containing a 960-bp coding region.
      Southern hybridization using aneuploid lines of T. aestivum 'Chinese Spring'
      indicated that CYP709C3v2 was located on the short arm of chromosomes 2B and 2D.

PMID- 15729395
TI  - Distribution of MWG699 polymorphism in Spanish European barleys.
AB  - The STS marker MWG699/TaqI is closely linked to the vrs1 locus and has been
      proposed as a marker of domestication in barley. This study included 257
      cultivated barleys of both two- and six-rowed varieties, mainly from the western
      Mediterranean region. These included many landraces from the Spanish barley core
      collection, Moroccan landraces, and a set of accessions from other European
      countries. Restriction analysis of amplified DNA revealed three alleles, as
      previously described. Most of the two-rowed entries had the same allele, type K.
      Six-rowed entries showed both types A and D. Indeed, type D was widespread among
      Spanish landraces and commercial varieties from central Europe. It was also found
      in some two-rowed landraces originating from Spain and Morocco. Barleys with the
      D haplotype were predominantly winter types, whereas the A haplotype was evenly
      distributed among spring and winter types. These results support the existence of
      two different genetic sources among six-rowed Spanish landraces.

PMID- 15729396
TI  - Insect mitochondrial genomics: the complete mitochondrial genome sequence of the
      meadow spittlebug Philaenus spumarius (Hemiptera: Auchenorrhyncha: Cercopoidae).
AB  - We present the complete mitochondrial genome sequence of the meadow spittlebug
      Philaenus spumarius (Auchenorrhyncha: Cercopoidae). This contribution represents
      the second mitochondrial genome from the Hemiptera and the second of the three
      hemipteran suborders sampled. The genome is a circular molecule of 16 324 bp with
      a total A+T content of 77.0% and 76.7% for coding regions only. The gene content,
      order, and structure are consistent with the Drosophila yakuba genome structure
      (Clary and Wolstenholme 1985) and the hypothesized ancestral arthropod genome
      arrangement (Crease 1999). Nucleotide composition and codon usage are near the
      means observed in other insect mitochondria sequenced to date but have a higher
      A+T richness compared with the other hemipteran example, the kissing bug Triatoma
      dimidiata (Dotson and Beard. 2001. Insect Mol. Biol. 10: 205-215). The major
      noncoding region (the A+T rich region or putative control region) between the
      small ribosomal subunit and the tRNAIle gene includes two extensive repeat
      regions. The first repeat region includes 19 tandem repeats of a 46-bp sequence,
      whereas the second contains a longer sequence (146 bp) tandemly repeated four
      times.

PMID- 15729397
TI  - Genetic diversity of the Andean tetraploid cultivated potato (Solanum tuberosum
      L. subsp. andigena Hawkes) evaluated by chloroplast and nuclear DNA markers.
AB  - Andigena potatoes (Solanum tuberosum L. subsp. andigena Hawkes) (2n = 4x = 48)
      are native farmer-selected important cultivars that form a primary gene pool of
      the common potato (Solanum tuberosum L. subsp. tuberosum). The genetic diversity
      of 185 Andigena accessions and 6 Chilean native potatoes (S. tuberosum subsp.
      tuberosum) was studied using chloroplast DNA (ctDNA) microsatellites and nuclear
      DNA (nDNA) restriction fragment length polymorphism (RFLP) markers. Andigena
      potatoes had 14 ctDNA haplotypes and showed higher variability in the central
      Andes, particularly in Bolivia, whereas those in the northern regions of the
      distribution area were remarkably uniform with A1 ctDNA and Chilean subsp.
      tuberosum with T ctDNA. Most of 123 clearly scored RFLP bands using 30 single
      copy probes were randomly distributed throughout the distribution area and proved
      the same gene pool shared among these widely collected accessions. Nevertheless,
      the geographic trend of the nDNA differentiation from north to south along the
      Andes and the correlated differentiation between nDNA and ctDNA (r = 0.120) could
      also be revealed by canonical variates analysis. These results suggest that the
      genetic diversity in Andigena was brought about primarily from cultivated diploid
      species but considerably modified through sexual polyploidization and
      intervarietal and (or) introgressive hybridization and long-distance dispersal of
      seed tubers by humans.

PMID- 15729398
TI  - A new intervarietal linkage map and its application for quantitative trait locus
      analysis of "gigas" features in bread wheat.
AB  - A doubled-haploid (DH) population from an intervarietal cross between the
      Japanese cultivar 'Fukuho-komugi' and the Israeli wheat line 'Oligoculm' was
      produced by means of wheat x maize crosses. One hundred seven DH lines were
      genotyped to construct a simple sequence repeat (SSR) based linkage map with
      RFLP, RAPD, and inter-simple sequence repeat markers. Out of 570 loci genotyped,
      330 were chosen based on their positions on the linkage map to create a
      "framework" map for quantitative trait locus (QTL) analysis. Among the 28 linkage
      groups identified, 25 were assigned to the 21 chromosomes of wheat. The total map
      length was 3948 cM, including the three unassigned linkage groups (88 cM), and
      the mean interval between loci was 12.0 cM. Loci with segregation distortion were
      clustered on chromosomes 1A, 4B, 4D, 5A, 6A, 6B, and 6D. After vernalization, the
      DH lines were evaluated for spike number per plant (SN) and spike length (SL) in
      a greenhouse under 24-h daylength to assess the "gigas" features (extremely large
      spikes and leaves) of 'Oligoculm'. The DH lines were also autumn-sown in the
      field in two seasons (1990-1991 and 1997-1998) for SN and SL evaluation. QTL
      analysis was performed by composite interval mapping (CIM) with the framework map
      to detect QTLs for SN and SL. A major QTL on 1AS, which was stable in both
      greenhouse and field conditions, was found to control SN. This QTL was close to
      the glume pubescence locus (Hg) and explained up to 62.9% of the total phenotypic
      variation. The 'Oligoculm' allele restricted spike number. The SSR locus Xpsp2999
      was the closest locus to this QTL and is considered to be a possible marker for
      restricted tillering derived from 'Oligoculm'. Eight QTLs were detected for SL.
      The largest QTL detected on 2DS was common to the greenhouse and field
      environments. It explained up to 33.3% of the total phenotypic variation. The
      second largest QTL on 1AS was common to the greenhouse and the 1997-1998 season.
      The position of this QTL was close to that for the SN detected on 1AS. The
      association between SN and SL is discussed.

PMID- 15729399
TI  - Genome relationships in polyploid Poa pratensis and other Poa species inferred
      from phylogenetic analysis of nuclear and chloroplast DNA sequences.
AB  - The genus Poa comprises approximately 500 species that occur throughout the
      world, including the widely grown Kentucky bluegrass (P. pratensis L.).
      Hybridization and polyploidization have played a prominent role in the evolution
      of this complex genus, but limited information is available regarding genome
      relationships in Poa. Thus, we amplified, cloned, and compared the DNA sequences
      of 2 nuclear genes (CDO504 and thioredoxin-like protein) and 2 chloroplast genome
      loci (ndhF and trnT-trnF) from 22 Poa species. Four distinct classes of sequences
      corresponding to 4 putative homoeologous loci from each nuclear gene were found
      within polyploid P. pratensis. Nuclear sequences from 15 other Poa species were
      found to group with at least 1 P. pratensis homoeolog, whereas 6 species
      displayed sequences not present in P. pratensis. The nuclear genome phylogenies
      presented here show the first evidence of diverse and related genomes in the
      genus Poa.

PMID- 15729400
TI  - Mapping of genes expressed in Fusarium graminearum-infected heads of wheat
      cultivar 'Frontana'.
AB  - The isolation, physical, and genetic mapping of a group of wheat genes expressed
      in infected heads of Triticum aestivum 'Frontana' resistant to Fusarium head
      blight is reported. A cDNA library was built from heads of 'Frontana' through
      suppressive subtractive hybridization, to enrich for sequences induced by the
      pathogen Fusarium graminearum during infection. A group of 1794 clones was
      screened by dot blot hybridization for differential gene expression following
      infection. Twenty of these clones showed a strong difference in intensity of
      hybridization between infected and mock-inoculated wheat head samples, suggesting
      that they corresponded to genes induced during infection. The 20 clones were
      sequenced and used for mapping analysis. We determined a precise chromosomal
      location for 14 selected clones by using series of chromosome deletion stocks. It
      was shown that the 14 clones detected 90 fragments with the use of the
      restriction enzyme EcoRI; 52 bands were assigned to chromosome bins, whereas 38
      fragments could not be assigned. The selected clones were also screened for
      polymorphisms on a 'Wuhan' x 'Maringa' wheat doubled haploid mapping population.
      One clone, Ta01_02b03, was related to a quantitative trait locus for type II
      resistance located on chromosome 2AL, as determined with simple sequence repeat
      markers on another mapping population, but did not map in the same location on
      our population. Another clone, Ta01_06f04, was identified by BLAST (basic local
      alignment search tool) search in public databases to code for a novel beta-1,3
      glucanase, homologous to a major pathogenesis-related protein. This clone mapped
      to chromosomal regions on chromosome 3, including 3BL and 3DL, where B glucanase
      gene clusters are known to exist. Seven other clones, including 1 coding for an
      ethylene-response element binding protein and 3 for ribosomal proteins, and 4
      clones corresponding to proteins with unknown function, were also mapped.

PMID- 15729401
TI  - Inheritance and QTL analysis of durable resistance to stripe and leaf rusts in an
      Australian cultivar, Triticum aestivum 'Cook'.
AB  - An F4-derived F6 recombinant inbred line population (n = 148) of a cross between
      the durable stripe (yellow) rust (caused by Puccinia striiformis) and leaf
      (brown) rust (caused by Puccinia triticina) resistant cultivar, Triticum aestivum
      'Cook', and susceptible genotype Avocet-YrA was phenotyped at several locations
      in Canada and Mexico under artificial epidemics of leaf or stripe rusts and
      genotyped using amplified fragment length polymorphism (AFLP) and microsatellite
      markers. Durable adult plant resistance to stripe and leaf rusts in 'Cook' is
      inherited quantitatively and was based on the additive interaction of linked and
      (or) pleiotropic slow-rusting genes Lr34 and Yr18 and the temperature-sensitive
      stripe rust resistance gene, YrCK, with additional genetic factors. Identified
      QTLs accounted for 18% to 31% of the phenotypic variation in leaf and stripe rust
      reactions, respectively. In accordance with the high phenotypic associations
      between leaf and stripe rust resistance, some of the identified QTLs appeared to
      be linked and (or) pleiotropic for both rusts across tests. Although a QTL was
      identified on chromosome 7D with significant effects on both rusts at some
      testing locations, it was not possible to refine the location of Lr34 or Yr18
      because of the scarcity of markers in this region. The temperature-sensitive
      stripe rust resistance response, conditioned by the YrCK gene, significantly
      contributed to overall resistance to both rusts, indicating that this gene also
      had pleiotropic effects.

PMID- 15729402
TI  - Genetic diversity of loquat germplasm (Eriobotrya japonica (Thunb) Lindl)
      assessed by SSR markers.
AB  - Genetic relationships among 40 loquat (Eriobotrya japonica (Thunb) Lindl)
      accessions that originated from different countries and that are part of the
      germplasm collection of the Instituto Valenciano de Investigaciones Agrarias
      (IVIA) (Valencia, Spain) were evaluated using microsatellites. Thirty primer
      pairs flanking microsatellites previously identified in Malus x domestica
      (Borkh.) were assayed. Thirteen of them amplified polymorphic products and
      unambiguously distinguished 34 genotypes from the 40 accessions analyzed. Six
      accessions showing identical marker patterns were Spanish local varieties thought
      to have been derived from 'Algerie' by a mutational process very common in loquat
      species. A total of 39 alleles were detected in the population studied, with a
      mean value of 2.4 alleles per locus. The expected and observed heterozygosities
      were 0.46 and 51% on average, respectively, leading to a negative value of the
      Wright's fixation index (-0.20). The values of these parameters indicate a
      smaller degree of genetic diversity in the set of loquat accessions analyzed than
      in other members of the Rosaceae family. Unweighted pair-group method (UPGMA)
      cluster analysis, based on Nei's genetic distance, generally grouped genotypes
      according to their geographic origins and pedigrees. The high number of alleles
      and the high expected heterozygosity detected with SSR markers developed in Malus
      x domestica (Borkh.) make them a suitable tool for loquat cultivar
      identification, confirming microsatellite marker transportability among genera in
      the Rosaceae family.

PMID- 15729403
TI  - Molecular cytogenetic identification of nullisomy 5B induced homoeologous
      recombination between wheat chromosome 5D and barley chromosome 5H.
AB  - Chromosome 5H of Hordeum vulgare 'New Golden' (NG) carries a gene(s) that
      accelerates heading in a wheat background. To introduce the early heading gene(s)
      of NG barley into the wheat genome, we attempted to induce homoeologous
      recombination between wheat and NG 5H chromosomes by 5B nullisomy. A nullisomic
      5B, trisomic 5A, monosomic 5H plant (2n = 42) was produced from systematic
      crosses between aneuploid stocks of wheat group 5 chromosomes. A total of 656 F2
      plants produced by self-fertilization were screened for recombinants by a PCR
      assay with 3 5H-specific amplicon markers. Twelve plants (1.8%) were selected as
      putative wheat-barley 5H recombinants. Five of them were inviable or sterile and
      the remaining 7 were fertile and subjected to the progeny test. Cytological
      analyses using fluorescence in situ hybridization and C-banding revealed that 6
      of the 7 progeny lines are true homoeologous recombinants between the long arms
      of chromosomes 5D and 5H, but that the other one was not a recombinant having an
      aberrant barley telosome. The 6 cytologically confirmed recombinant lines
      included only 2 types (3 lines each), which were reciprocal products derived from
      exchanges at the same distal interval defined by two flanking markers. One type
      had a small 5HL segment translocated to the 5DL terminal, and the other type had
      a small terminal 5DL segment translocated to the 5HL terminal. In the latter
      type, the physical length of translocated barley segments slightly differed among
      lines. Homoeologous recombinants obtained in this study should be useful for
      further chromosome manipulation to introgress a small interstitial 5HL chromosome
      segment with the early heading gene(s) to wheat. Preferential occurrence of
      restricted types of recombinants is discussed in relation to homoeologous
      relationships between wheat and barley chromosomes.

PMID- 15729404
TI  - Genomic analysis of a region encompassing QRfs1 and QRfs2: genes that underlie
      soybean resistance to sudden death syndrome.
AB  - Candidate genes were identified for two loci, QRfs2 providing resistance to the
      leaf scorch called soybean (Glycine max (L.) Merr.) sudden death syndrome (SDS)
      and QRfs1 providing resistance to root infection by the causal pathogen Fusarium
      solani f.sp. glycines. The 7.5 +/- 0.5 cM region of chromosome 18 (linkage group
      G) was shown to encompass a cluster of resistance loci using recombination events
      from 4 near-isogenic line populations and 9 DNA markers. The DNA markers anchored
      9 physical map contigs (7 are shown on the soybean Gbrowse, 2 are unpublished),
      45 BAC end sequences (41 in Gbrowse), and contiguous DNA sequences of 315, 127,
      and 110 kbp. Gene density was high at 1 gene per 7 kbp only around the already
      sequenced regions. Three to 4 gene-rich islands were inferred to be distributed
      across the entire 7.5 cM or 3.5 Mbp showing that genes are clustered in the
      soybean genome. Candidate resistance genes were identified and a molecular basis
      for interactions among the disease resistance genes in the cluster inferred.

PMID- 15729405
TI  - Molecular characterization and chromosomal localization of female-specific genes
      from the Mediterranean fruit fly Ceratitis capitata (Diptera: Tephritidae).
AB  - We report here the molecular characterization of the female-specific FST (female
      specific transcript) genes from the Mediterranean fruit fly (medfly) Ceratitis
      capitata. A genomic clone was isolated, containing a sequence coding for FST.
      Nucleotide analysis of the clone showed that the gene contains a putative unique
      intron located in the region encoding the signal peptide. Southern blotting and
      in situ hybridization analysis on polytene chromosomes suggested the presence of
      additional genes similar to FST in the genome of the medfly. A novel cDNA clone
      was isolated from an accessory gland cDNA library, encoding a product that shares
      98% identity with the hypothetical translational product of the previously
      isolated FST cDNA. The novel cDNA was therefore named FST2. The analysis of
      mitotic and polytene chromosomes by in situ hybridization showed that FST genes
      map on the left arm of the 4th chromosome of C. capitata.

PMID- 15729406
TI  - FISH-aimed karyotyping and characterization of Renner complexes in permanent
      heterozygote Rhoeo spathacea.
AB  - Fluorescence in situ hybridization (FISH) using 25S rDNA, 5S rDNA, and telomere
      sequences as probes was carried out in the complex permanent heterozygote Rhoeo
      spathacea. Telomere sites were exclusively terminal. All 10 25S rDNA loci were
      located distally and appeared transcriptionally active after silver staining. Six
      distal and 2 interstitial 5S rDNA sites were detected; 2 of the distal sites
      strictly colocalized with 25S rDNA loci. The 2 intercalary 5S rDNA loci occurred
      in short arms of 2 chromosomes that conjoined at meiosis. Chromosomes differed as
      to the amount of AT-rich centric heterochromatin, suggesting involvement of
      pericentromeric regions in translocations. The possibility of Robertsonian-like
      rearrangements was discussed. Double target FISH with ribosomal probes along with
      DAPI fluorescence gave the basis for full chromosome identification in mitosis.
      The 2 Renner complexes are structurally balanced, both having 5 25S and 4 5S rDNA
      sites. Centromere clustering, telomere association, a high number of NOR sites,
      and a strong tendency for formation of joint nucleoli contribute to the
      preservation of highly polarized Rabl arrangement at interphase. These findings
      were discussed in relation to meiotic catenation in Rhoeo.

PMID- 15729407
TI  - The genomic composition of Tricepiro, a synthetic forage crop.
AB  - Chromosome in situ hybridization (FISH and GISH) is a powerful tool for
      determining the chromosomal location of specific sequences and for analysing
      genome organization and evolution. Tricepiro (2n = 6x = 42) is a synthetic cereal
      obtained by G. Covas in Argentina (1972), which crosses hexaploid triticale (2n =
      6x = 42) and octoploid Trigopiro (2n = 8x = 56). Several years of breeding
      produced a forage crop with valuable characteristics from Secale, Triticum, and
      Thinopyrum. The aim of this work is to analyse the real genomic constitution of
      this important synthetic crop. In situ hybridization using total DNA of Secale,
      Triticum, and Thinopyrum as a probe (GISH) labelled with biotin and (or)
      digoxigenin showed that tricepiro is composed of 14 rye chromosomes and 28 wheat
      chromosomes. Small zones of introgression of Thinopyrum on wheat chromosomes were
      detected. The FISH using the rye repetitive DNA probe pSc 119.2 labelled with
      biotin let us characterize the seven pairs of rye chromosomes. Moreover, several
      wheat chromosomes belonging to A and B genomes were distinguished. Therefore,
      tricepiro is a synthetic hexaploid (2n = 6x = 42) being AABBRR in its genomic
      composition, with zones of introgression of Thinopyrum in the A genome of wheat.

PMID- 15729408
TI  - Phylogenetic roots of Alu-mediated rearrangements leading to cancer.
AB  - There are over a million Alu repetitive elements dispersed throughout the human
      genome, and a high level of Alu-sequence similarity ensures a strong propensity
      for unequal crossover events, some of which have lead to deleterious oncogenic
      rearrangements. Furthermore, Alu insertions introduce consensus 3' splice sites,
      which potentially facilitate alternative splicing. Not surprisingly, Alu-mediated
      defective splicing has also been associated with cancer. To investigate a
      possible correlation between the expansion of Alu repeats associated with primate
      divergence and predisposition to cancer, 4 Alu-mediated rearrangements--known to
      be the basis of cancer--were selected for phylogenetic analysis of the necessary
      genotype. In these 4 cases, it was determined that the different phylogenetic age
      of the oncogenic recombination-prone genotype reflected the evolutionary history
      of Alu repeats spreading to new genomic sites. Our data implies that the
      evolutionary expansion of Alu repeats to new genomic locations establishes new
      predispositions to cancer in various primate species.

PMID- 15729409
TI  - Genomic characterization and physical mapping of two fucosyltransferase genes in
      Medicago truncatula.
AB  - Fucosyltransferases catalyse fucose transfer onto oligosaccharides. Two
      fucosylated structures have been identified in plants: the alpha1,4-fucosylated
      Lewis-a epitope and the alpha1,3-fucosylated core. Here we report the cloning,
      genomic characterization, and physical mapping of two genes encoding proteins
      similar to alpha1,4-fucosyltransferase (EC 2.4.1.65, MtFUT1) and alpha1,3
      fucosyltransferase (EC 2.4.1.214, MtFUT2) in Medicago truncatula. Analysis of the
      genomic organization of the fucosyltransferase genes in M. truncatula, revealed
      the presence of two genomic variants of the MtFUT1 gene coding sequence, one
      containing a single intron and the other intronless, whereas in MtFUT2, the gene
      coding region is interrupted by four introns. Using for the first time
      fluorescence in situ hybridization (FISH) to physically map fucosyltransferase
      genes in plants, this study reveals a high genomic dispersion of these genes in
      Medicago. The MtFUT1 genes are mapped on chromosomes 4, 7, and 8, colocalizing on
      three of the five MtFUT2 loci. Chromosomes 1 and 5 carry the additional MtFUT2
      loci. Moreover, the intensity of the FISH signals reveals marked differences in
      the number of gene copies per locus for both genes. Simultaneous mapping of rRNA
      genes on chromosome 5 shows that several MTFUT2 gene loci are inserted within the
      rDNA array. Insertions of coding DNA sequences into the rDNA repeats were never
      reported to date.

PMID- 15729412
TI  - The practice gap.

PMID- 15729410
TI  - Endonuclease banding reveals that atrazine-induced aneuploidy resembles
      spontaneous chromosome loss in Crassostrea gigas.
AB  - Aneuploidy has previously been observed in the Pacific oyster, Crassostrea gigas,
      and shown to be negatively correlated with growth. Moreover, a significant impact
      of atrazine exposure has been described in C. gigas, and persistence of that
      effect has been observed between generations. Evidence of differential chromosome
      loss has been demonstrated in aneuploid karyotypes of C. gigas using the G
      banding technique. Pairs 1, 5, 9, and 10 are characterized by the loss of 1
      chromosome. As restriction enzyme (RE) digestion chromosome banding allows a
      better identification of chromosome pairs, we used this technique to identify
      which chromosomes are affected when aneuploidy is increased by exposure to
      atrazine. The progeny of oysters contaminated by atrazine were analysed using the
      restriction enzyme HaeIII. The study of 26 RE-banded aneuploid karyotypes showed
      that the same chromosome pairs (1, 5, 9, and 10) were affected by the loss of 1
      chromosome (61%, 15%, 42%, and 42%, respectively). Further investigation is
      required to enable a better understanding of aneuploidy in oysters, especially
      with respect to why some chromosomes are more easily lost than others, and why
      cells tolerate the loss of these chromosomes.

PMID- 15729413
TI  - Acute treatment of myocardial infarction in Canada 1999-2002.
AB  - BACKGROUND: Therapy for management of acute myocardial infarction (AMI) varies
      according to patient, prescriber and geographical characteristics. OBJECTIVES: To
      describe the in-hospital use of reperfusion therapy for ST elevation MI (STEMI)
      and discharge use of acetylsalicylic acid, beta-blockers, angiotensin-converting
      enzyme inhibitors (ACEIs) and statins in patients presenting with either STEMI or
      non-STEMI in Canada from 1999 to 2002. METHODS: Four Canadian registries (FASTRAK
      II, Canadian Acute Coronary Syndromes, Enhanced Feedback for Effective Cardiac
      Treatment and Improving Cardiovascular Outcomes in Nova Scotia) were used to
      identify patients with AMI in Canada and to measure in-hospital reperfusion and
      medication use. Use rates were compared by age, sex, time period and geographical
      area, according to available data. RESULTS: Use rates for reperfusion in STEMI
      patients ranged from 60% to 70%, primarily representing fibrinolytic therapy. A
      delay in presentation to hospital after symptom onset represented an impediment
      to timely therapy, which was particularly pronounced for women and elderly
      patients. Overall, less than 50% of patients met the door-to-needle target of
      less than 30 min. Medication use rates at discharge increased from 1999/2000 to
      2000/2001 across the different data sources: acetylsalicylic acid, 83% to 88%;
      beta-blockers, 74% to 89%; ACEIs, 54% to 67%; statins, 41% to 53%; and calcium
      antagonists, 21% to 32%. CONCLUSIONS: Canadian and provincial rates of use of
      evidence-based medications for the treatment of AMI have increased over time,
      although there remains room for improvement. A single, comprehensive data source
      would supply better insights into the management of AMI in Canada.

PMID- 15729414
TI  - ST segment resolution predicts clinical outcome and response to dobutamine
      testing after primary percutaneous transluminal coronary angioplasty.
AB  - AIM: To assess clinical outcome and improvement in left ventricular (LV)
      contractility during a six-month follow-up after successful primary percutaneous
      transluminal coronary angioplasty (PTCA), according to rapid ST segment
      resolution. The usefulness of early dobutamine echocardiography (DE) in the
      prediction of LV functional recovery in patients treated with primary PTCA was
      tested. PATIENTS AND METHODS: One hundred ten consecutive patients with first
      acute myocardial infarction after successful primary PTCA (Thrombolysis in
      Myocardial Infarction (TIMI) 3 flow and stenosis of less than 30%) were divided
      into two groups according to whether ST segment resolution occurred 1 h after the
      procedure. The patients underwent clinical assessment and echocardiography
      (ejection fraction [EF] and wall motion index [WMI]) after primary PTCA, during
      DE on the fourth day of hospitalization, and again after three and six months.
      RESULTS: In patients with ST segment resolution (n=76 [69.1%]), LVEF increased
      significantly during the six-month follow-up (P=0.0001). Changes found in the
      group without ST segment resolution were insignificant (P=0.4). Early DE in
      patients with rapid ST segment resolution revealed significant improvements in LV
      contractility measured by EF and WMI. Patients without ST segment resolution had
      a higher incidence of death (three of 34 [8.8%] versus zero of 76 [0%],
      P=0.0086), reinfarction (five of 34 [14.7%] versus two of 76 [2.6%], P=0.28) and
      revascularization (four of 34 [11.8%] versus three of 76 [3.9%], P=0.12). The
      combined end point (death, reinfarction and revascularization) was significantly
      lower in patients with ST segment resolution (P=0.03). CONCLUSIONS: Rapid ST
      segment resolution is associated with LV contractility recovery, and a better
      clinical outcome and prognosis after successful primary PTCA. Early DE after
      primary PTCA predicts LV functional recovery. Patients with ST segment resolution
      are likely to respond to early dobutamine testing.

PMID- 15729415
TI  - Declining need for permanent pacemaker insertion with the bicaval technique of
      orthotopic heart transplantation.
AB  - BACKGROUND: The bicaval technique of orthotopic heart transplantation, in
      contrast to the standard biatrial technique, may better preserve right atrial
      anatomy and, thus, may be associated with less sinus node dysfunction and less
      atrioventricular valve dysfunction. OBJECTIVES: To compare the requirement for
      permanent pacemaker insertion and the incidence of atrioventricular valve
      dysfunction following heart transplantation with either the standard or the
      bicaval technique. PATIENTS AND METHODS: A retrospective analysis was conducted
      of a consecutive cohort of 105 patients, older than 18 years of age, undergoing
      heart transplantation with either the standard (n=48) or the bicaval (n=57)
      technique from December 1998 to December 2001. RESULTS: Cross-clamp (100 min
      versus 112 min; P=0.012) and donor ischemic (222 min versus 276 min; P=0.005)
      times were significantly prolonged in the bicaval group. Perioperative morbidity
      and mortality were statistically similar between the groups. Bicaval
      transplantation resulted in a significant decrease in the requirement for
      permanent pacemaker insertion at 30 days (13% versus 0%; P=0.008) and 90 days
      (17% versus 1.8%; P=0.01) after transplantation. There was a nonsignificant trend
      toward a decreased degree of tricuspid valve regurgitation (mean 1.81 versus
      1.36; P=0.141) and mitral valve regurgitation (mean 1.04 versus 0.79; P=0.348)
      with the bicaval technique. CONCLUSIONS: Although associated with longer cross
      clamp and donor ischemic times, the data demonstrated a significant reduction in
      the need for permanent pacemaker insertion at 30 and 90 days post-transplantation
      with the bicaval technique. There was no statistically significant difference in
      the degree of mitral and tricuspid valve regurgitation between the two groups.

PMID- 15729416
TI  - The interaction among sex, hemoglobin and outcomes in a specialty heart failure
      clinic.
AB  - PURPOSE: Although anemia has recently been demonstrated to be a marker for poor
      outcomes in patients with congestive heart failure (CHF), the impact of sex on
      the prevalence and prognostic impact of anemia has not been adequately explored.
      Accordingly, the relationship among sex, anemia and outcomes in CHF was analyzed.
      SUBJECTS: Patients seen at a specialty CHF clinic from 1989 to 2001. METHODS: A
      retrospective analysis of prospectively collected data was performed using chi2
      and Student's t tests to determine the association between anemia and mortality.
      Multivariate Cox proportional hazards models were used to measure the independent
      association of anemia with mortality in men and women. The World Health
      Organization definition of anemia (less than 130 g/L for men; less than 120 g/L
      for women) and the Centers for Disease Control and Prevention definition of
      anemia (less than 135 g/L for men, less than 120 g/L for women) were used, and
      hemoglobin was assessed as a continuous variable. RESULTS: There were 791
      patients with CHF seen over a 12-year period (median age 69 years, median
      hemoglobin of 131 g/L [interquartile range 119 to 144 g/L]) and 34% were women.
      The demographics and treatments were similar for men and women, except that women
      were older (69 years versus 65 years, P<0.001), more likely to have a nonischemic
      etiology of CHF (P<0.001) or diastolic dysfunction (P<0.001), and lower
      creatinine clearances (P<0.001). Forty per cent of men and 35% of women were
      anemic using the World Health Organization definition. Anemia was associated with
      a one-year and five-year excess mortality in men (adjusted OR 1.7 [1.1 to 2.5]
      and 1.76 [1.2 to 2.7], respectively), but this was not observed in women
      (adjusted OR 1.2 [0.7 to 2.2] and 1.2 [0.7 to 2.1], respectively). CONCLUSIONS:
      Anemia is prevalent in heart failure and predicts mortality in men but not in
      women. Given this result, the authors recommend that randomized trials evaluating
      novel therapies for the correction of anemia in patients with heart failure
      should stratify their randomization by sex.

PMID- 15729418
TI  - Thoracic endovascular stent grafts.

PMID- 15729417
TI  - Changing trends in management of thoracic aortic disease: where do we stand with
      thoracic endovascular stent grafts?
AB  - BACKGROUND: Descending thoracic aortic surgery is linked to a high morbidity and
      mortality. Thoracic endovascular stent grafts were designed to decrease
      perioperative risks, especially in patients with severe comorbidities. However,
      procedure-related complications and clinical outcomes remain ill-defined.
      PATIENTS AND METHODS: The authors' experience in 24 patients (mean age 63.3+/
      25.4 years) from May 2001 to February 2004 is reported. The diagnosis was
      thoracic aneurysm in 10 patients, complicated penetrating aortic ulcer in six
      patients, blunt traumatic aortic rupture in four patients, complicated type B
      dissection in two patients, and aortoesophageal fistula and postoperative
      pseudoaneurysm in one patient each, respectively. Symptoms were present in 15 of
      24 patients (62.5%). The decision to implant a thoracic endovascular stent graft
      was based on significant coinjuries in three patients, severe comorbidities in 16
      patients and patient decision in five patients. RESULTS: The mean operative time
      was 2.3+/-1.7 h and the mean number of stents per patient was 1.8+/-0.7. Six
      patients required coverage of the left subclavian artery without complications. A
      carotid-carotid bypass was required in two patients. In one patient, a thoracic
      endovascular stent graft was introduced through a 10 mm graft anastomosed to the
      distal descending aorta accessed through a video-assisted minithoracotomy.
      Perioperative complications were an arterial access problem in one patient and
      pneumonia in four patients. The primary success rate was 100%. An 82-year-old
      patient with a ruptured thoracoabdominal aneurysm died of multi-organ failure
      (4.1% hospital mortality). All 23 surviving patients were alive at 13.4+/-3.5
      months. One patient required an additional procedure for recurrent hematemesis.
      CONCLUSIONS: Thoracic endovascular stent grafts show excellent early results in
      well-selected cases. Extra-anatomical bypass or novel vascular access procedures
      increase the applicability of thoracic endovascular stent grafts. Meticulous
      follow-up is essential to identify and treat stent graft-related complications.
      Data on long-term outcomes are required before applying thoracic endovascular
      stent grafts to patients with a lower operative risk.

PMID- 15729419
TI  - Reversible left ventricular dysfunction (takotsubo cardiomyopathy) with deep
      negative T waves due to possible cardiac sympathetic denervation.
AB  - A case of characteristic left ventricular contraction disorder representing
      takotsubo cardiomyopathy after exercise is reported. A 58-year-old Japanese woman
      with no history of cardiac disease was admitted for chest oppression after
      exercise. A diagnosis of myocardial infarction was suspected because of her
      symptom, and the electrocardiographic and echocardiographic findings. Coronary
      angiography revealed normal arteries, while left ventriculography demonstrated
      asynergy with apical akinesis and basal hyperkinesis. Deep negative T waves were
      observed on the electrocardiogram on the second hospital day and sustained for
      over a month. Repeated measurements of heart rate viability and 123I
      metaiodobenzylguanidine scintigraphy showed transient dysfunction of the cardiac
      autonomic nervous system. From these findings, it was concluded that cardiac
      autonomic denervation plays a pivotal role in the etiology of takotsubo
      cardiomyopathy.

PMID- 15729420
TI  - A case of primary malignant pericardial mesothelioma.
AB  - Primary malignant pericardial mesothelioma (PMPM) is an exceedingly rare tumour.
      One of the largest necropsy series gave an incidence of primary pericardial
      tumours of 0.0022%, of which mesothelioma is the most common type. In a Canadian
      epidemiological survey, the annual incidence of PMPM was reported to be one in 40
      million. A male predominance of the disease has been described, and the majority
      of cases occur in the fourth to seventh decades of life. There has been no
      definite association between asbestos exposure and pericardial disease. Due to
      its generally late presentation and poor response to therapy, the prognosis is
      very poor. The present report discusses the case of a 43-year-old man who
      presented with cardiac tamponade and was subsequently diagnosed with PMPM.
      Cardiac tamponade is a known complication of the malignancy, but it is rarely the
      first manifestation of cancer. The patient's clinical course was a result of the
      aggressive nature of PMPM. Effusive constrictive pericarditis and restrictive
      cardiomyopathy were likely contributors to this patient's disease burden. These
      processes should be considered and managed appropriately in patients who do not
      respond to pericardiocentesis or pericardial window as treatment for pericardial
      tamponade.

PMID- 15729421
TI  - Should all patients with peripheral arterial disease be treated with an
      angiotensin-converting enzyme inhibitor?
AB  - Peripheral arterial disease (PAD) is a marker of advanced atherosclerosis with an
      elevated risk of cardiovascular mortality and morbidity. The modification of risk
      factors to improve the outcomes of patients with coronary artery atherosclerosis
      is proven and has become an accepted standard of care that is widely followed.
      Recent evidence from randomized controlled clinical trials has demonstrated the
      effectiveness of angiotensin-converting enzyme inhibitors as an important risk
      reduction therapy for patients with PAD. This therapy has yet to become well
      recognized and implemented in the PAD population. This article reviews the
      evidence that supports the use of angiotensin-converting enzyme inhibitors in
      patients with PAD to reduce the burden of the associated cardiovascular morbidity
      and mortality in this high-risk population.

PMID- 15729422
TI  - Painful legs, aching heart: Reducing cardiovascular risk in patients with
      peripheral arterial disease with angiotensin-converting enzyme inhibition.

PMID- 15729423
TI  - Genetic aspects of diabetes and its cardiovascular complications: contribution of
      genetics to risk assessment and clinical management.
AB  - Diabetes mellitus is a source of great concern in contemporary cardiology. It is
      a heterogeneous disease and patients are often characterized by features of the
      insulin resistance syndrome, also referred to as the metabolic syndrome. The
      objectives of the present review were to discuss some genes that potentially
      modulate the risk of coronary artery disease in diabetes mellitus; to address how
      the genes' respective contributions could possibly influence the global risk
      assessment of coronary artery disease among diabetic patients; and to present
      simple clinical markers, such as plasma glycerol concentration and the
      'hypertriglyceridemic waist' phenotype, that could help to identify high-risk
      individuals.

PMID- 15729425
TI  - Beyond the scope of conflict of interest.

PMID- 15729426
TI  - Passing scopes: A right or a privilege?

PMID- 15729427
TI  - Estimating the cost of illness in colorectal cancer patients who were
      hospitalized for severe chemotherapy-induced diarrhea.
AB  - BACKGROUND: Previous studies have suggested that grade III/IV diarrhea is a
      common complication in colorectal cancer, occurring in 20% to 30% of patients
      receiving chemotherapy. In some of these patients, hospitalization for supportive
      care is often required. However, the impact that these hospitalized patients have
      on overall use of health care resources has not been quantified. In the present
      study, a cost of illness analysis was conducted to estimate the overall cost of
      patients with colorectal cancer who were hospitalized for supportive care
      secondary to severe diarrhea. METHODS: This was a retrospective cohort study
      consisting of patients with colorectal cancer that had received
      fluoropyrimidines, irinotecan or oxaliplatin (or a combination thereof) and had
      developed grade III or IV diarrhea that resulted in hospital admission for
      supportive care. Data collection included patient demographics, disease-related
      information and use of health care resources to manage the grade III/IV diarrhea
      event. RESULTS: Patients had a mean age of 64.2 years, and 32 of 63 (50.8%) were
      receiving adjuvant chemotherapy with a curative intent. The severe diarrhea
      developed after the first cycle of chemotherapy in 58% of the patients and
      contributed to a dose reduction, change or discontinuation of chemotherapy in
      9.5%, 15.9% and 34.2% of patients, respectively. Overall, the median length of
      hospital stay was eight days (range one to 49 days) translating to a mean cost of
      $8,230 per patient (95% CI $6,519 to $9,942). The diarrhea successfully resolved
      in 54 of 63 patients (85.7%). CONCLUSIONS: Severe diarrhea requiring hospital
      admission is a costly and potentially fatal complication of chemotherapy in
      colorectal cancer. The identification of predictive factors and the
      implementation of prophylactic measures could reduce the morbidity and mortality
      associated with diarrhea.

PMID- 15729428
TI  - The increasing prevalence of Crohn's disease in industrialized societies: the
      price of progress?
AB  - Crohn's disease (CD) is an idiopathic inflammatory condition of the
      gastrointestinal system. While inflammation can activate one of a number of
      specific branches of the immune system, CD promotes a T helper cell type 1 (Th1)
      profile. The prospect that CD is a form of Th1-dominant autoimmune disease is
      gaining acceptance, with support from the current use of immunosuppressants.
      Recently, convincing evidence that the various branches of the immune system have
      the ability to keep each other in check has suggested that the Th1 profile of CD
      may stem from a greatly reduced T helper cell type 2 (Th2) immune response. A
      strong Th2 immune response is a characteristic of the once prevalent enteric
      parasitic diseases, now nearly eradicated from industrial society. This has led
      to the acceptance of a hygiene hypothesis, which suggests that the inverse
      relationship between CD and the level of a society's industrialization is, in
      fact, causal - that the lack of parasitic infections causes a weakened systemic
      Th2 cytokine profile, leading to elevated Th1 cytokines and, ultimately, the
      development of spontaneous Th1-mediated diseases such as CD. Supporting this, it
      has been recently demonstrated that an experimentally-induced Th2 response can
      help moderate Th1-dominant events in both animal and human studies. Based on this
      recent and convincing work, the present review focuses on the role of
      immunoregulation in the development of CD, with particular emphasis on the
      potential use of Th2-promoting agents (such as helminths or cytokines) as
      therapeutics in the treatment or prevention of CD.

PMID- 15729429
TI  - Reflections on education--machines or mentors: mentors and mentorship. Education
      Excellence Lecture 2004.

PMID- 15729430
TI  - Gastroduodenal intussusception secondary to a gastric lipoma.
AB  - Gastroduodenal intussusception caused by a gastric lipoma is an uncommon
      condition, and only a few cases have been reported in the medical literature. A
      case of a 72-year-old man who complained of weight loss and intermittent episodes
      of nausea and vomiting is presented. Diagnostic workup demonstrated a mass in the
      second portion of the duodenum. The patient underwent a diagnostic laparoscopy
      followed by an exploratory laparotomy that confirmed the gastroduodenal
      intussusception by a gastric lipoma. In addition, the anatomical and clinical
      presentation, diagnosis and management of this entity are discussed.

PMID- 15729431
TI  - Cytomegalovirus infection in a patient with Crohn's ileocolitis.
AB  - Cytomegaloviral enterocolitis is an uncommon infection that can complicate
      inflammatory bowel disease. A case of a patient with a three-year history of
      Crohn's disease is reported. He had been in a stable condition on mesalamine 4
      g/day and methylprednisolone 10 mg/day for three years until four weeks before
      admission. The patient was admitted with complaints of fever, abdominal pain and
      watery diarrhea. A diagnosis of an exacerbation of Crohn's disease was
      established. The radiological examination revealed narrowing of the terminal
      ileum. Multiple fistulas and abscess-like images were observed. The patient then
      underwent ileocolic resection and ileostomy. The histopathological examination
      revealed Crohn's ileocolitis with superimposed cytomegalovirus infection. In
      patients with rapidly deteriorating inflammatory bowel disease, cytomegalovirus
      infection should be kept in mind as one of the differential diagnoses.

PMID- 15729434
TI  - [Alcohol: from public health to psychiatric comorbidity].

PMID- 15729435
TI  - [Epidemiology of alcohol use in Brazil].
AB  - The authors describe the most recent and significant epidemiological studies on
      alcohol conducted in Brazil in the last years. The aim was to outline the pattern
      of alcohol consumption in the country through the analysis of population surveys
      (household surveys, drug abuse among students, homeless children) and statistical
      indicators (hospital admissions for addictions, data from the Institute of
      Forensic Medicine, related traffic accidents and information on sales of
      alcoholic beverages). The analysis of the data presented in this article suggests
      two basic points: greater emphasis should be laid on epidemiological studies in
      Brazil, through increasing the scope of research, as well as its systematic
      updating. Alcohol certainly has a strong influence in the etiology and
      maintenance of several social, economic and health problems faced in our country.

PMID- 15729436
TI  - [The social and health burden of alcohol abuse].
AB  - Based on the recent report on alcohol-related health and social burdens issued by
      the World Health Organization (WHO), this paper explores and discusses the
      evidence in support of the view that concerns about alcohol consumption extend
      far beyond consideration of personal and family health consequences, but should
      be considered in the context of major socio-political and public health
      priorities. The global findings of the WHO report are first discussed, followed
      by analysis of the specific findings regarding the burden of alcohol problems in
      Brazil. The social burden of alcohol problems is quantified by applying a
      unifying methodology which incorporates outcomes for alcohol-related violence,
      family problems, child abuse, public disorder, lost productivity, and other
      consequences. By analyzing the epidemiological date on alcohol-related morbidity
      and mortality data from each continental region and sub-region, and cross
      tabulating data on average consumed volume and patterns of consumption, the
      burden of disease are estimated for the various regions of the world. The final
      results provide a comparative analysis of risk, basically using a representative
      indicator of number of productive years lost because of illness or premature
      mortality due to alcohol consumption ("DALYs" -- Disability Adjusted Life Years).
      The DALYs global value in 2000 was 4% of world mortality, with this rate
      predicted to increase as global alcohol consumption increases. Variations among
      various regions in the planet are critically analyzed on predictive factors.

PMID- 15729437
TI  - [Alcohol Dependence Syndrome: diagnostic criteria].
AB  - The Alcohol Dependence Syndrome (ADS) is a serious problem of public health. In
      spite of being deeply studied and having well-established diagnostic criteria,
      many times clinicians and even psychiatrists do not notice this disorder. The aim
      of this paper is to make a brief exposition on how men and society have developed
      their relationship with alcohol, emphasizing the development of the concept of
      alcoholism in medicine until the definition of ADS in ICD-10 and DSM-IV. The
      article explains the different ways of alcohol consume and how it influences
      different levels of risk and severity of its consequences, that evolves as a
      continuum. At last, it makes a comparison between ADS and alcohol harmful use,
      very important in the prevention and treatment of such disorders.

PMID- 15729438
TI  - [Alcohol use among adolescents: concepts, epidemiological characteristics and
      etiopatogenic factors].
AB  - Alcohol is the most consumed substance among young people, and the onset of its
      use is starting at an earlier age, raising the risks of future dependence. The
      use of alcohol in adolescence is associated with a series of risk behaviors,
      besides raising the risk of involvement in accidents, sexual violence, and
      participating in gangs. Alcohol use by adolescents is strongly associated with
      violent death, poor academic performance, learning difficulties and damage in the
      development and structuring of cognitive-behavioral and emotional abilities.
      Alcohol consumption causes neurochemical modifications, with damage in memory,
      learning and impulse control. Professionals who deal with adolescents must be
      prepared for a thorough evaluation regarding the possible abusive use or
      dependence of alcohol in this age group. However, it is important to emphasize
      that the criteria utilized by some diagnostic tools for abuse and dependence were
      developed for adults, and must be applied with caution in adolescents. Thus, it
      is fundamental that these professionals be aware of the characteristics and
      peculiarities of adolescence and chemical dependence in this age-group.

PMID- 15729439
TI  - [From one beer with friends to alcohol dependence: a synthesis about our
      knowledge of this path].
AB  - Review paper about prospective studies concerning the natural history of
      alcoholism. Emphasizing Vaillant and the impact of his contribution to the
      evolution of the concepts of harmful use and dependence, as well as its most
      important therapeutic implications. The fact that the abstinence rates, in the
      treatment of a severe dependence, almost remaining the same in the last twenty
      five years is highlighted.

PMID- 15729440
TI  - [Neurocognitive assessment in alcohol abuse and dependence: implications for
      treatment].
AB  - The aim of the Neuropsychology applied to the Alcohol Dependence field is the
      comprehension of the effects of brain dysfunction on cognition and human
      behavior. It investigates neurocognitive impairments and associates them to
      structural and functional neuroimaging findings (CT, MRI, PET and SPECT). Acute
      use of alcohol impairs attention, memory, executive functions and visuospatial
      skills, while chronic abuse causes neurocognitive deficits in memory, learning,
      visuospatial functions, psychomotor speed processing, executive functions and
      decision-making, and may lead to persistent amnesic disorder and alcoholic
      dementia. Executive Dysfunction related to frontal lobe has direct implications
      on treatment, by the choosing of strategies and for prognostic evaluation. It is
      presented an easy tool to screen cognitive impairments, the Frontal Assessment
      Battery--FAB.15. Neuropsychological Assessment is useful for early detection of
      impairments and evaluation of their evolution and Cognitive Rehabilitation has a
      significant role on deficits recovery and psychosocial adjustment of these
      patients.

PMID- 15729441
TI  - [Brief interventions for alcohol related problems].
AB  - This article presents the concepts and basic premises that are necessary for a
      better understanding of the Brief Interventions (BIs), with a literature review
      of its effectiveness and a discussion about BIs in Brazil. The theoretical
      premises are discussed, as well the concepts represented by the acronym FRAMES:
      Feedback; Responsibility; Advice; Menu; Empathic and Self-efficacy. Results of
      systematic reviews and metanalysis about BIs effectiveness are discussed and a
      summary box with the main studies is presented. Finally, the recent developments
      about the introduction of BIs in Brazil are commented. The importance of health
      professionals training and the adoption of BIs within different settings are
      emphasized considering its demonstrated effectiveness and economic feasibility.

PMID- 15729442
TI  - [Cognitive and Cognitive-Behavioral Therapy for substance abuse disorders].
AB  - This article describes the current status of Cognitive and Behavioral Therapy as
      well Relapse Prevention and Coping Skill approaches applied in drug abuse
      treatments. The objective is show a review about theories and technique used by
      Cognitive Therapy and others approaches derived that, specifically Relapse
      Prevention and Coping Skill Treatments. Cognitive and Behavioral Therapy, Coping
      Skill, and Relapse Prevention are a short-time, goal-oriented and structured
      treatments. Thus, they assume a posture directive and active. We pointed out some
      difference between the theories about Cognitive Therapy, Relapse Prevention and
      Coping Skill. The Cognitive Therapy accentuated the focus in patients thought,
      feeling and circumstances that get in a dysfunctional behavioral. Relapse
      Prevention and Coping Skill are based in behavioral theories besides of the
      Cognitive. We, finally, look forward to introduce the lasted scientific finding
      to helpful the general psychiatric to improve the assistance in drug abuse
      treatment.

PMID- 15729443
TI  - [Neuropharmacological aspects of chronic alcohol use and withdrawal syndrome].
AB  - The objective of this paper is to review and describe the main
      neuropharmacological changes caused by the chronic use of alcohol and those
      observed during its withdrawal period. The results show international data
      referring to the involvement of monoamine systems, neurotransmitters and calcium
      channels in both neuroadaptation and tolerance to alcohol effects and withdrawal.
      Relevant studies showing the participation of other systems in those mechanisms,
      as opioids and other substances, are also shown. The article reinforces the
      importance, for both physicians and researchers, of an always growing
      understanding of alcohol central mechanisms of action. This understanding is
      necessary to new pharmacological options to alcohol harm reduction as well as to
      alcohol withdrawal treatment.

PMID- 15729444
TI  - [The pharmacologic treatment of the alcohol dependence].
AB  - The pharmacological intervention can play a crucial role in the reduction of
      craving and drinking and the maintenance of abstinence. This article reviews
      pharmacotherapy for alcohol dependence with an emphasis on the naltrexone,
      dissulfiram and acamprosate. The opioid antagonist naltrexone lowers relapse
      rate, reduces drinking days and prolongs periods of abstinence. Acamprosate
      restores the normal activity of glutamate and GABA systems. Disulfiram has been
      shown to be most effective for patients who believe in its efficacy and remain
      compliant with the treatment. Ondansetron, has shown promise in the early-onset
      alcohol dependence but needs more extensive study. Topiramate (up to 300 mg per
      day) was more efficacious than placebo in the treatment of alcohol dependence.

PMID- 15729445
TI  - [Psychiatric complications of alcoholism: alcohol withdrawal syndrome and other
      psychiatric disorders].
AB  - Alcohol withdrawal syndrome is an acute condition secondary to total or partial
      reduction of alcohol consumption, characterized by self limited signs and
      symptoms and different degrees of severity. It can be complicated by several
      clinical and/or other psychiatric related problems. The objective of this article
      is to review the most important psychiatric complications to alcohol withdrawal
      syndrome as well as other psychiatric disorders associated with alcohol
      dependence as Wernicke Korsakoff and Marchiava Bignami syndromes. We aim to
      promote early diagnosis and treatment of these conditions, minimizing morbidity
      and mortality associated with them.

PMID- 15729446
TI  - [Comorbidity: alcohol use and other psychiatric disorders].
AB  - Alcohol related disorders often coexist with other psychiatric disorders and its
      incidence is increasing in last decades. Studies show that patients with
      comorbidity, specially those with severe psychiatric disorders, have higher rates
      of suicide, relapse, money spent in treatment, homeless and they use more medical
      service. Their evaluation must be meticulous because the differential diagnosis
      become complicated without a long period of alcohol withdrawal. These patients
      have a worse prognostic and their treatment is more difficult. Most of studies in
      this area have indicated that the integration of psychosocial and pharmacological
      techniques is more effective. The long term treatment must focus in the reduction
      of symptoms, improvement of social and familiar functioning, coping skills and
      relapse prevention.

PMID- 15729447
TI  - [The role of genetics in alcohol dependence].
AB  - In this article we examined the heritability of alcohol dependence. A review of
      family, twin and adoption studies, allowed us to support the thesis of an
      important genetic component in this dependence. The transmission of this
      heritability occurs through a biological vulnerability associated to
      environmental factors, in a model called epigenetic. We also discussed the
      relationship between biological vulnerability and high-risk phenotypes for
      alcohol dependence. In the end, we briefly comment on the molecular genetic
      studies associated with this disorder.

PMID- 15729448
TI  - [Services organization for the treatment of alcohol dependence].
AB  - The problems related to the consumption of alcohol vary along a gravity
      continuum. Such a characteristic requests the construction of treatment services
      that assist to the needs in each one of these situations. Besides, the economical
      and cultural context of a given community covers the patient of particularities
      that need to be considered by the service of treatment. This way, the
      organization of services for the treatment of the dependence of the alcohol
      should begin for the determination of the structure interns of the institution
      and its place inside of the net of available attention. The whole construction
      should be based on the needs of the population-objective (obtained by diagnostic
      evaluations) and implemented with evaluations and constant monitoring of the
      wanted impact. Presently, manuals and guidelines available online aid and
      facilitate the execution of these actions.

PMID- 15729449
TI  - [Case management applied to the treatment of alcohol dependence].
AB  - This article aims is to conceptualize and describe the main steps in case
      management applied to the treatment of alcohol dependence. It is important to
      note the case manager functions, the importance of the first appointment, check
      the motivation to the treatment, some goals and activities suggestions for
      adherence reinforcement.

PMID- 15729450
TI  - [Brazilian consensus on public policies on alcohol].
AB  - This is the summary of a meeting where a group of experts, representing several
      health organizations and academic departments from different parts of Brazil,
      created a consensus about the main alcohol policies which should be implemented
      by different levels of the Brazilian government. The World Health Organization
      has been suggesting for 30 years the actions that should be implemented for the
      public good. Two important conclusions were reached: 1) The research establishes
      beyond doubt that public health measures of proven effectiveness are available to
      serve the public good by reducing the widespread costs and pain related to
      alcohol use; 2) To that end, it is appropriate to deploy responses that influence
      both the total amount of alcohol consumed by a population and the high-risk
      contexts and drinking behaviours that are so often associated with alcohol
      related problems. To conceive of these intrinsically complementary approaches as
      contractory alternatives would be a mistake. The objectives of the consensus are:
      1) To make the scientific evidences more available to the Brazilian policy
      makers; 2) To facilitate the evaluation of the available strategies according
      their effectivity, scientific support, cost and cultural adaptability; 3) To make
      the Brazilian health professionals familiar with the priorities of alcohol
      policies.

PMID- 15729451
TI  - [Autoimmunity in obsessive-compulsive disorder and tic disorders].

PMID- 15729452
TI  - [PANDAS--Pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infection: is it a specific clinical disorder?].

PMID- 15729453
TI  - [PANDAS: overview of the hypothesis].

PMID- 15729454
TI  - [PANDAS: to treat or not to treat?].

PMID- 15729456
TI  - [Willingness and alternatives to drunk driving among young people from Sao Paulo
      city, Brazil].
AB  - The new Brazilian Traffic Code considers drinking and driving as a traffic crime.
      A health behavior model suggests that much of the young people's risky behavior
      is not planned and that questions measuring the willingness to drink and drive
      are useful. In face of the importance of drinking and driving as a national
      health problem, the objective of the present study was to analyze the behavior
      willingness among youngsters about to receive their driver's licenses. METHODS:
      The study was carried out at the Sao Paulo Department of Traffic (DETRAN-SP) in
      1998. Data were obtained from a sample of 2,166 youths, 18 to 25 years old, who
      took the written drivers' license examination. Data about, among other things,
      alcohol consumption, willingness and alternatives to drinking and driving in the
      following year was examined. RESULTS: In general, individuals displayed
      willingness to both the risky behavior (drunk driving) and to the safe behavior
      (alternatives as taking a cab or getting a ride). Regression analyzes were done
      by dividing the sample in three groups. Several significant differences were
      found between the groups, suggesting that the attitudes and behaviors went on a
      direction from safer to riskier from groups 1 to 3. CONCLUSION: Findings suggest
      that prevention efforts presenting a spectrum of alternatives to drunk driving
      and the enforcement of drink and driving laws would be two useful addenda to the
      more severe laws created in the 1998 Traffic Code.

PMID- 15729455
TI  - [A comparative study of norms for a 400 picture set between Brazilian and
      American children].
AB  - OBJECTIVE: This study compared Brazilian and North American children regarding
      naming, familiarity and visual complexity of a set of 400 pictures. METHOD:
      Thirty-six Brazilian children (18 boys) aged 5 to 7 were evaluated. Their
      characteristics and the study procedure and measures were the same as those
      employed for the North American population enabling direct comparison of data
      from the two samples through Spearman rho correlations and Student t tests.
      RESULTS: Positive significant correlations between overall results of Brazilian
      and North American children were observed for all measures. Qualitative analysis
      showed that both groups gave modal names that differed from the intended names
      for the same 59 pictures. The Brazilian children named 72 pictures differently
      from the intended names that were correctly named by the North American children,
      who named 26 pictures differently from the intended names that were correctly
      named by the Brazilians. CONCLUSION: The 400 picture set was shown to be an
      adequate tool for use in different cultures. However, it is advisable to avoid
      pictures that produced naming inconsistencies by the Brazilian and North American
      children in studies in other cultures with the same age group until specific
      norms are made available.

PMID- 15729457
TI  - [Body mass index, body weight perception and common mental disorders among
      university employees in Rio de Janeiro].
AB  - OBJECTIVE: We tested the hypothesis that inadequate self-perception of body
      weight with or without obesity would be associated with common mental disorders
      (CMD). METHOD: We analyzed cross-sectional data from 4,030 university employees
      participating in the longitudinal Pro-Saude Study Phase 1 (1999) in Rio de
      Janeiro. Participants (22-59 years of age) were invited to fill out a
      questionnaire that includes an evaluation of common mental disorders by General
      Health Questionnaire (GHQ-12). Body mass index (BMI=kg/m2) was calculated based
      on measured weight and height, and participants self-classified their own current
      body weight as highly above ideal, slightly above ideal, ideal, slightly below
      ideal or highly below ideal. RESULTS: Among woman 58.3% of those with body mass
      index lower than 25.0 kg/m2 considered themselves as being above ideal weight;
      for men, this proportion was 23.5%. Multivariate logistic regression adjusted for
      age, income, leisure-time physical activity, self-reported health problem and
      body mass index, showed that body weight perception highly above ideal had a
      strong association with common mental disorders among women (OR=1.84, 95%CI=1.22
      2.76). For women but not men, body mass index showed a borderline association
      with common mental disorders (p-trend=0.05) that did not persist after adjustment
      for income and self-reported health problem. CONCLUSION: Inadequate body weight
      perception, independent of body mass index, was associated with common mental
      disorders in women, but not men. One possible explanation for this association
      may be the socio-cultural pressure placed on women to conform the thinness ideal.

PMID- 15729458
TI  - [Comorbid eating disorders in a Brazilian attention-deficit/hyperactivity
      disorder adult clinical sample].
AB  - Although comorbidity between attention-deficit/hyperactivity disorder (ADHD) and
      eating disorders (ED) is relevant for clinical treatment, it is seldom
      investigated. METHODS: 86 DSM-IV attention deficity hyperactivity disorder
      patients out of 107 self-referred adults in a specialized center for attention
      deficity hyperactivity disorder were interviewed using SCID-R to evaluate the
      lifetime prevalence of ED and other comorbid conditions. RESULTS: Nine attention
      deficity hyperactivity disorder patients had comorbid eating disorders; binge
      eating disorder (BED) was the most common diagnosis. The group with eating
      disorders presented a higher prevalence of other comorbid disorders (p=0.02). No
      significant differences were found on gender, age at assessment, schooling level
      and type of attention deficity hyperactivity disorder between groups. CONCLUSION:
      Attention deficity hyperactivity disorder clinical samples may have a high
      prevalence of BED comorbidity. Patients with attention deficity hyperactivity
      disorder and eating disorders may have a different comorbid profile.

PMID- 15729459
TI  - [Anxiety and depression symptoms assessment in pre-term neonates' mothers during
      and after hospitalization in neonatal intensive care unit].
AB  - OBJECTIVE: To identify clinical level of anxiety, dysphoria and depression
      symptoms of pre-term infants' mothers between two moments, during and after
      hospitalization in Neonatal Intensive Care Unit (NICU). METHODS: Previously,
      mothers with psychiatric background were excluded of the study. Forty-three pre
      term and very low birthweight infants' mothers were assessed through State-Trait
      Anxiety Inventory and Beck Depression Inventory. The assessments were done during
      and after hospitalization, respectively. RESULTS: In the first assessment, 44%
      mothers showed clinical level in one or more of the emotional symptoms, such as
      anxiety, dysphoria or depression. After infants' discharge, the number of mothers
      with clinical level of emotional symptoms decreased significantly (26%) in
      comparison of the first assessment (p< or =0.008). The anxiety-state level
      decreased significantly from the first to the second assessment (from 35% to 12%;
      p< or =0.006). No difference in depression and dysphoria symptoms between two
      assessments were found. CONCLUSION: The pre-term infants' mothers presented
      situational anxiety and required emotional support to cope with the infants'
      hospitalization.

PMID- 15729460
TI  - [Brazilian-Portuguese version of the Defense Style Questionnaire (DSQ-40) for
      defense mechanisms measure: a preliminary study].
AB  - The aim of this study is to describe the translation and adaptation process of
      the Defense Style Questionnaire (DSQ-40) into Brazilian-Portuguese version. The
      instrument has also contended validation evaluation. METHODS: The first version
      of the scale was presented to five individuals with different schooling for
      language adaptation. Afterwards the instrument was presented to three experts
      that evaluated its content validation. The final version was back-translated and
      accepted by the original author. RESULTS: Vocabulary adjustments were needed in 9
      items and language adaptation in 4 items in order to render the final DSQ-40
      Brazilian-Portuguese version. The mean of experts' correlation to each defense
      was 89%, being 100% to mature, neurotic and immature factors. CONCLUSION: The
      adaptation of DSQ-40 by different individuals and the group of experts enabled
      the necessary adjustment to the Brazilian socio-cultural reality.

PMID- 15729461
TI  - [Brazilian guideline for the treatment of patients with opioids dependence
      syndrome].
AB  - There is a relatively low prevalence of opioid use in Brazil, particularly
      involving the non-medical use of codeine and opiate-containing syrups. However,
      opioid dependence syndrome shows a significant total impact on mortality and
      morbidity. Over the past 20 years, scientific progress has changed our
      understanding of the nature of opioid addiction and its various possible
      treatments. Addiction is a chronic illness treatable if the treatment is well
      delivered and tailored to the needs of the particular patient. There is indeed an
      array of treatments that can effectively reduce drug use, help manage drug
      cravings, prevent relapses and restore people to productive social functioning.
      The treatment of drug addiction will be part of long-term, medical,
      psychological, and social perspectives. This guideline aims at providing guidance
      to psychiatrists and other mental health professionals who care for patients with
      opioid dependence syndrome. It comments on the somatic and psychosocial treatment
      that is used for such patients, and reviews scientific evidences and their
      strength. Also, the essential historical, epidemiological and neurobiological
      aspects of opioid dependence are reviewed.

PMID- 15729462
TI  - [Genetics of autism].
AB  - Autism is a neuropsychiatric disorder with profound family and social
      consequences. An extraordinary number of genetical-clinical, cytogenetics and
      molecular studies were done in recent years. A multiloci epistatic model involved
      in the causation of autism have emerged from these studies.

PMID- 15729463
TI  - [Oppositional defiant disorder: a review of neurobiological and environmental
      correlates, comorbidities, treatment and prognosis].
AB  - Oppositional defiant disorder (ODD) is an independent diagnostic entity but it is
      frequently studied in conjunction with Attention-Deficit Hyperactivity Disorder
      (ADHD) or Conduct Disorder (CD). The purpose of this paper is to review the
      extant evidence, through the PubMed database, on the neurobiological correlates
      of oppositional defiant disorder and also describe the familiar and school
      functioning, comorbidities, prognosis and therapeutic options for oppositional
      defiant disorder. Evidence of hormonal, genetic and neuro-functional findings in
      oppositional defiant disorder, correlation with the family, school relations and
      performance, and the association with mood and anxiety and disruptive disorders
      are described. The risk of an evolution to conduct disorder and of persistence of
      the oppositional defiant disorder symptoms is depicted. A review of the effect of
      Cognitive-Behavioral Therapy and medication is presented. Analysis of the
      available evidence shows that the impact of oppositional defiant disorder should
      not be ignored and it should be properly addressed. The effect of treatment for
      oppositional defiant disorder on the long-term outcome of patients still needs to
      be addressed.

PMID- 15729464
TI  - [Unexplained clinical-neurological symptoms may indicate depressive syndromes].

PMID- 15729465
TI  - [Lack of association between a polymorphism of the norepinephrine transporter
      gene and schizophrenia in a Brazilian sample].

PMID- 15729466
TI  - [Considerations about echolalia in children with Asperger's syndrome: proposing
      an approach for language therapeutics].

PMID- 15729467
TI  - Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children
      failing highly active antiretroviral therapy (HAART).
AB  - The aim of this study was to evaluate the genotypic resistance profiles of HIV-1
      in children failing highly active antiretroviral therapy (HAART). Forty-one
      children (median age = 67 months) receiving HAART were submitted to genotypic
      testing when virological failure was detected. cDNA was extracted from PBMCs and
      amplified by nested PCR for the reverse transcriptase and protease regions of the
      pol gene. Drug resistance genotypes were determined from DNA sequencing.
      According to the genotypic analysis, 12/36 (33.3%) and 6/36 (16.6%) children
      showed resistance and possible resistance, respectively, to ZDV; 5/36 (14%) and
      4/36 (11.1%), respectively, showed resistance and possible resistance to ddI;
      4/36 (11.1%) showed resistance to 3TC and D4T; and 3/36 (8.3%) showed resistance
      to Abacavir. A high percentage (54%) of children exhibited mutations conferring
      resistance to NNRTI class drugs. Respective rates of resistance and possible
      resistance to PIs were: RTV (12.2%, 7.3%); APV (2.4%, 12.1%); SQV(0%, 12.1%); IDV
      (14.6%, 4.9%), NFV (22%, 4.9%), LPV/RTV (2.4%, 12.1%). Overall, 37/41 (90%)
      children exhibited virus with mutations related to drug resistance, while 9%
      exhibited resistance to all three antiretroviral drug classes.

PMID- 15729468
TI  - Persistence of Vectobac WDG and Metoprag S-2G against Aedes aegypti larvae using
      a semi-field bioassay in Rio de Janeiro, Brazil.
AB  - Persistence of Bacillus thuringiensis var. israelensis (Vectobac WDG) and
      methoprene (Metoprag S-2G) was evaluated against Aedes aegypti late third instar
      larvae of the Rockefeller strain in a semi-field bioassay. Tests were performed
      in Rio de Janeiro, using containers made of plastic, iron, concrete and asbestos,
      placed in a shaded area. The formulations used were 0.2 g of Vectobac-WDG and 1 g
      of Metoprag S-2G per 100 liters of water in house storage containers. Vectobac
      WDG was tested twice, in March and in April/May, 2002. In March (temperature
      ranging from 21.5 to 39.3 degrees C), 70-100% mortality was observed by the 7th
      day and declined abruptly thereafter. No significant differences were observed
      among the container types. In April/May (18.6 to 34.8 degrees C) mortality was
      higher than 70% to 30-36 days in all cases, except in the iron container (40%
      mortality on the 12th day). Metoprag S-2G was evaluated in April/May, 2002, and
      induced mortality higher than 70% up to 15 days in the plastic and iron
      containers and only seven days in the concrete container. In the asbestos
      container, maximal mortality was achieved on day one post-treatment (66%). Our
      results point to a low persistence of both formulations in the weather conditions
      of Rio de Janeiro.

PMID- 15729469
TI  - Clinical laboratory assessment of hepatitis C and HIV coinfected patients
      according to the antiretroviral therapy received.
AB  - During the year of 2001, a retrospective, descriptive study in order to determine
      the influence of the antiretroviral therapy received by 111 HIV-HCV coinfected
      patients who had undergone at least one liver biopsy was conducted, 74 of them
      were treated with a protease inhibitor regimen (WPI), and 37 with a non-protease
      inhibitor regimen (NPI). The main characteristics found were: a young patient
      population (mean age 41 years old in both groups), composed in most part of male
      individuals (74.3% WPI and 51.4% NPI) with previous risk factors for both
      infections (WPI 93.2% and NPI 89.2%). The most significant findings included AIDS
      defining disease (WPI 18.9% and NPI 13.5% of the cases), elevated hepatic enzyme
      levels (WPI: SGOT 52.1 and NPI 53.2), absence of liver disease-related symptoms
      (16.2% for both groups), average CD4 count > 350 for both groups (WPI 362.2 and
      NPI 378.1), predominantly low-grade fibrosis in both populations (0-2 in 63.6% of
      WPI patients and in 80% of NPI patients), with necro-inflammatory activity
      ranging from 5-7 in 51.3% and 42.9% of WPI patients and NPI patients,
      respectively. It is suggested a sequential biopsy to better evaluate the
      evolution of the hepatic disease, according to the HAART regimen received.

PMID- 15729470
TI  - Staphylococcus aureus ampicillin-resistant from the odontological clinic
      environment.
AB  - The aim of this research was to evaluate the prevalence of Staphylococcus spp.
      and S. aureus in the odontological clinic environment (air), their production of
      beta-lactamase and antibacterial susceptibility to the major antibiotics utilized
      in medical particle. During 12 months of samples collect were isolated 9775 CFU
      by MSA medium suggesting a high amount of Staphylococcus spp. in the clinic
      environment which can appear through aerosols. A total of 3149 colonies (32.2%)
      were suggestive of pathogenic staphylococci. Gram coloration, catalase test,
      colony-mallow growing on chromogenic medium, and coagulase test confirmed the
      identity of 44 (0.45%) S. aureus isolates. Of these, 35 isolates (79.5%) showed
      production of beta-lactamase by Cefinase discs and resistance to ampicillin,
      erythromycin (7 isolates) and tetracycline (1 isolate) suggesting the existence
      of multiresistant isolates. The evaluation of the oxacillin MIC by Etest assays
      showed susceptibility patterns suggesting the inexistence of the mecA gene in
      chromosomal DNA. These results point out to the need of a larger knowledge on the
      contamination means and propagation of this microorganism into the odontological
      clinic.

PMID- 15729471
TI  - Cutaneous anthrax in Lima, Peru: retrospective analysis of 71 cases, including
      four with a meningoencephalic complication.
AB  - Anthrax is a zoonosis produced by Bacillus anthracis, and as an human infection
      is endemic in several areas in the world, including Peru. More than 95% of the
      reported naturally acquired infections are cutaneous, and approximately 5% of
      them can progress to meningoencephalitis. In this study we review the clinical
      and epidemiological characteristics of the patients with diagnosis of cutaneous
      anthrax evaluated between 1969 and 2002 at the Hospital Nacional Cayetano Heredia
      (HNCH) and the Instituto de Medicina Tropical Alexander von Humboldt in Lima,
      Peru. Seventy one patients were included [49/71 (69%) of them men], with a mean
      age of 37 years. The diagnoses were classified as definitive (44%) or probable
      (56%). The most common occupation of the patients was agriculture (39%). The
      source of infection was found in 63 (88.7%) patients. All the patients had
      ulcerative lesions, with a central necrosis. Most of the patients (65%) had
      several lesions, mainly located in the upper limbs (80%). Four patients (5.6%)
      developed meningoencephalitis, and three of them eventually died. In conclusion,
      considering its clinical and epidemiological characteristics, cutaneous anthrax
      must be included in the differential diagnosis of skin ulcers. A patient with
      clinical suspicion of the disease should receive effective treatment soon, in
      order to avoid neurological complications which carry a high fatality rate.

PMID- 15729472
TI  - Environmental strains of Cryptococcus neoformans variety grubii in the city of
      Santos, SP, Brazil.
AB  - This study involved a total of 116 samples, 79 taken from pigeon droppings and 37
      of atmospheric air taken close to accumulations of excrement. Cryptococcus
      neoformans var. grubii was isolated from 11 (13.9%) of these samples. Other
      species of Cryptococcus were also isolated from these samples, such as C. albidus
      (12.6%) and C. laurentii (8.9%). C. neoformans was not isolated from the air
      samples, though C. albidus (5.4%) was. All the strains of C. neoformans were
      found to belong to the A serotype (C. neoformans var. grubii). In regard to the
      studies with the antifungal agents 5-fluorocytosine, fluconazole, itraconazole,
      amphotericin B and voriconazole, by means of the microdilution method (EUCAST),
      we point out that one sample demonstrated resistance to fluconazole, this being
      especially significant because this is an environmental strain.

PMID- 15729473
TI  - Incidence of respiratory viruses in preterm infants submitted to mechanical
      ventilation.
AB  - The objectives of this study were to determine the incidence of infection by
      respiratory viruses in preterm infants submitted to mechanical ventilation, and
      to evaluate the clinical, laboratory and radiological patterns of viral
      infections among hospitalized infants in the neonatal intensive care unit (NICU)
      with any kind of acute respiratory failure. Seventy-eight preterm infants were
      studied from November 2000 to September 2002. The newborns were classified into
      two groups: with viral infection (Group I) and without viral infection (Group
      II). Respiratory viruses were diagnosed in 23 preterm infants (29.5%); the most
      frequent was respiratory syncytial virus (RSV) (14.1%), followed by influenza A
      virus (10.2%). Rhinorrhea, wheezing, vomiting and diarrhea, pneumonia,
      atelectasis, and interstitial infiltrate were significantly more frequent in
      newborns with nosocomial viral infection. There was a correlation between
      nosocomial viral infection and low values of C-reactive protein. Two patients
      with mixed infection from Group I died during the hospital stay. In conclusion,
      RSV was the most frequent virus in these patients. It was observed that, although
      the majority of viral lower respiratory tract infections had a favorable course,
      some patients presented a serious and prolonged clinical manifestation,
      especially when there was concomitant bacterial or fungal infection.

PMID- 15729474
TI  - On the possibility of autochthonous Chagas disease in Roraima, Amazon region,
      Brazil, 2000-2001.
AB  - Chagas disease has been almost entirely eradicated from the arid zones in Central
      and Northeastern Brazil where rare or no autochthonous cases have been reported.
      However, in the last 10 years the disease has increasingly been registered in the
      Amazon Region. Aiming to investigate the possibility of the occurrence of
      autochthonous cycle of Chagas disease in Roraima, triatomine collections,
      vectorial susceptibility studies (this one to be shown elsewhere),
      parasitological and serological analyses were conducted in three agricultural
      settlement areas (Rorainopolis, Passarao Project and Ilha Community). Blood-donor
      candidates were also investigated. This is the first epidemiological survey on
      Chagas disease conducted in agricultural settlements in Roraima. Triatomine
      species found were Triatoma maculata, Rhodnius pictipes, Rhodnius robustus and
      Panstrongylus geniculatus. Trypanosoma cruzi detection analyses included
      xenodiagnosis, indirect immunofluorescence, indirect hemaglutination, ELISA and
      kinetoplast PCR amplification. Natural triatomine infection was not found in
      intestinal contents. Twenty-five adult settlers (1.4% out of 1821, all > 15 year
      old, 20 migrants) presented anti-T. cruzi antibodies. Two migrant settlers (from
      Minas Gerais and Maranhao) tested positive for more than two serological tests,
      besides either being positive for xenodiagnosis or PCR. Results show that Chagas
      disease is not endemic in the areas studied. However, all elements of the
      transmission cycle are present, demanding for an adequate and continuous
      vigilance.

PMID- 15729475
TI  - Subcutaneoous phaeohyphomycosis by Exophiala jeanselmei in a cardiac transplant
      recipient.
AB  - We report a case of phaeohyphomycosis caused by Exophiala jeanselmei in a cardiac
      transplant recipient maintained on immunosuppressive therapy with mycophenolate
      mofetil tacrolimus and prednisone. The lesion began after trauma on the right leg
      that evolved to multiple lesions with nodules and ulcers. Diagnosis was performed
      by histological examination and culture of pus from skin lesions. Treatment
      consisted of itraconazole (200 mg/day) for three months with no improvement and
      subsequently with amphotericin B (0.5 mg/Kg per day to a total of 3.8 g
      intravenously). After four months of treatment, the lesions showed marked
      improvement with reduction in the swelling and healing of sinuses and residual
      scarring.

PMID- 15729477
TI  - Transvaginal suture placement for bleeding control with the tension-free vaginal
      tape procedure.
AB  - Tension-free vaginal tape (TVT) is a well-established surgical procedure for the
      treatment of female urinary stress incontinence. The operation, described by
      Ulmsten in 1995, is based on a midurethral Prolene tape support. TVT is accepted
      as an easy-to-learn and safe minimally invasive surgical technique.
      Intraoperative bleeding was described as complicating former surgical methods for
      correction of female urinary stress incontinence as well as TVT. The aim of this
      paper was to describe a simple transvaginal hemostatic suture placement to
      control accidental intraoperative hemorrhage. Of 566 patients undergoing TVT and
      followed for up to 68 months, 9 (1.6%) had intraoperative bleeding of 200-800 ml,
      all of which were diagnosed and corrected among the first 466 procedures. The
      last 100 patients had a transvaginal hemostatic suture placed whenever more than
      minimal bleeding occurred and hemostasis was achieved immediately with all. The
      benefit of this minimal, fast, and simple surgical step is assessed and
      discussed.

PMID- 15729476
TI  - Combined urinary and faecal incontinence.
AB  - Combined urinary and faecal (liquid or solid) incontinence (double incontinence)
      is the most severe and debilitating manifestation of pelvic floor dysfunction.
      The community prevalence is 9-19% (urinary) and 5-10% (faecal), increasing with
      age. Pathophysiological factors include childbirth-associated external anal
      sphincter injury and pudendal nerve damage, pelvic floor descent, menopause,
      collagen disorders and multiple sclerosis-like conditions. The presence of
      crossed reflexes between the bladder, urethra, anorectum and pelvic floor in
      animal studies may explain the comorbidity of urinary and faecal urgency.
      Surgical treatment is based on aetiology and combined optimum techniques such as
      colposuspension or suburethral sling with overlapping sphincteroplasty. Other
      methods for improving sphincteric control include sacral nerve neuromodulation,
      bulking agents and artificial sphincters.

PMID- 15729478
TI  - The perspective of the International Osteoporosis Foundation on the official
      positions of the International Society for Clinical Densitometry.

PMID- 15729480
TI  - Molecular basis of group A streptococcal pyrogenic exotoxin B.

PMID- 15729479
TI  - Assessment of risk factors for second hip fractures in Japanese elderly.
AB  - In an attempt to identify a cohort with a high risk of suffering a fracture of
      the contralateral hip (second hip fracture), we assessed patients who had
      suffered hip fracture. A total of 714 patients (130 men and 584 women) were
      prospectively followed to determine those who suffered a second hip fracture.
      Pathologic hip fractures and fractures that emerged from high-energy trauma were
      excluded from the analysis. Age, gender, Singh Index (SI), fracture type,
      cognitive impairment, and comorbid medical conditions were investigated as
      medical predictors. The 714 patients were observed for 1,579.5 person-years
      (mean: 2.4+/-1.4 years per patient). During the observation period, 45 second hip
      fractures were identified (bilateral group), giving an overall incidence of 0.029
      per person-year. The annual incidence rate declined linearly from the occasion of
      the initial fracture. Furthermore, the second hip fracture tended to occur
      increasingly within 8 months after the initial hip fracture. The second hip
      fracture was of the same type (trochanteric or cervical) in 79% of the
      trochanteric and 71% of the cervical fractures. There was no significant
      difference in the incidence of second hip fracture by gender or age. In addition,
      there was no significant difference in the distribution of SI grades of the
      unfractured hip at the initial hip fracture between the 669 patients who had not
      suffered a second hip fracture (unilateral group) and the bilateral group. Cox
      proportional hazard regression analysis revealed that increased risk of a second
      hip fracture was associated with senile dementia and Parkinson's disease. We
      concluded that careful follow-up of hip fracture patients associated with senile
      dementia and Parkinson's disease might effectively prevent the incidence of a
      second hip fracture.

PMID- 15729481
TI  - In vitro activity of beta-lactams and quinolones against AmpC beta-lactamase
      producing Escherichia coli.
AB  - We studied the antimicrobial susceptibility of AmpC beta-lactamase-producing
      Escherichia coli isolates collected at ten medical institutions in the Kinki area
      of Japan during a 6-month period (November 2002 through April 2003). Of 2845 E.
      coli isolates tested, 29 (1.0%) showed a minimum inhibitory concentration (MIC)
      for cefazolin of more than 8 microg/ml and were three-dimensional extract test
      positive. In standard inoculum susceptibility tests against these 29 strains, the
      MIC90s for the four carbapenems tested ranged from 0.06 microg/ml to 0.5
      microg/ml, and these compounds were more active than the other beta-lactams, with
      meropenem being the most active. The MIC90s for beta-lactams, except carbapenems,
      ranged from 4 microg/ml to 32 microg/ml, with cefepime being the most active. In
      high inoculum susceptibility tests against these strains, the MIC90s for the four
      carbapenems and cefepime were 8 microg/ml or less, and these compounds were more
      active than other beta-lactams. The MIC90s for beta-lactams, except carbapenems
      and cefepime, were 32 microg/ml or more. The MIC90s for the five quinolones
      tested ranged from 4 microg/ml to 16 microg/ml, and the order of increasing
      susceptibility was ciprofloxacin > levofloxacin, gatifloxacin and pazufloxacin >
      prulifloxacin.

PMID- 15729482
TI  - The effect of fosfomycin on nedaplatin-induced nephrotoxicity in rats.
AB  - The effect of coadministration of fosfomycin (FOM) on nedaplatin-induced
      nephrotoxicity in rats was investigated for 6 days. FOM decreased nedaplatin
      induced nephrotoxicity, as shown by reduced blood urea nitrogen (BUN), serum
      creatinine levels, and urinary excretion of N-acetyl-beta-D-glucosaminidase
      (NAG). Further, there were fewer histopathological signs of nephrotoxicity in the
      groups treated with the combination of nedaplatin and FOM as compared with the
      nedaplatin-alone group. The concentration of nedaplatin was significantly lower
      in the renal cortex of rats treated with the combination of nedaplatin and FOM as
      compared with those treated with nedaplatin alone (p < 0.05). In conclusion, the
      concomitant administration of FOM and nedaplatin may help to achieve a
      chemotherapeutic strategy that reduces the nephrotoxic effects of nedaplatin.

PMID- 15729483
TI  - Kinetic analysis of Mycobacterium tuberculosis-specific cytokine production by
      PBMC in adults after BCG vaccination.
AB  - Although bacille Calmette-Guerin (BCG) has been used worldwide as the only
      vaccine for tuberculosis, its protective efficacy in human adults is
      controversial. To investigate human immunological responses to Mycobacterium
      tuberculosis after BCG vaccination, we analyzed IFN-gamma and IL-10 production by
      peripheral blood mononuclear cells (PBMC) from health-care workers five times
      throughout the year after BCG vaccination. Of 449 health-care workers, 36 (8.0%)
      were negative by the tuberculin skin test, and of these, 20 were vaccinated with
      BCG. Because all the subjects had received BCG vaccination as infants, the
      present vaccination was considered to be a revaccination. The cytokine responses
      of the vaccinated and control tuberculin skin-test-positive subjects (n = 6) were
      followed at 0, 2, 4, and 8 weeks and at 12 months. The mean IFN-gamma production
      by PBMC when cultured with purified protein derivative (PPD) gradually increased,
      reached a peak at week 8, and then declined until 12 months, with four exceptions
      who showed no IFN-gamma elevation. The IFN-gamma level of the vaccinated group at
      week 0 was significantly lower than that of the controls. The mean IL-10
      production in response to PPD reached a peak at week 2, and then declined to its
      lowest point at week 8. These results indicate that the BCG vaccine can induce a
      type I cytokine response to M. tuberculosis in most tuberculin skin-test-negative
      adults at week 8, suggesting the immunological efficacy of vaccination.

PMID- 15729484
TI  - Pharmacokinetics of panipenem/betamipron in patients with end-stage renal
      disease.
AB  - Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for
      the treatment of severe and intractable bacterial infections caused by gram
      positive and gram-negative bacteria. Because 30% of panipenem and most of the
      betamipron are excreted in the urine in an unchanged form, renal function is the
      important determinant of the dosage regimen of panipenem/betamipron. In this
      study, the pharmacokinetics of panipenem/betamipron were investigated in patients
      with end-stage renal disease (ESRD) undergoing hemodialysis treatment to
      establish an appropriate dose regimen. We further attempted to predict the in
      vivo clearance in patients undergoing hemodialysis based on the in vitro
      dializability. The pharmacokinetics of panipenem/betamipron were investigated in
      eight patients after a 1-h intravenous infusion of panipenem/betamipron (500
      mg/500 mg). The in vitro extraction ratios of panipenem/betamipron through a high
      flux dialyzer were obtained, and compared with those obtained in vivo. The
      clearances of panipenem in patients were 9.53 +/- 1.26 l/h with hemodialysis, and
      2.92 +/- 0.238 l/h without hemodialysis. In contrast, those of betamipron were
      4.18 +/- 0.643 l/h and 0.615 +/- 0.511 l/h, respectively. The clearance of
      panipenem with hemodialysis were predicted well from in vitro extraction ratios,
      while that of betamipron was overestimated about 1.4-fold, probably due to high
      plasma protein binding and the binding difference between patients and healthy
      subjects. After comparing the pharmacokinetic behavior of panipenem in patients
      with ESRD and that of a surrogate marker of efficacy, we recommend that these
      patients be treated with 500 mg/500 mg of panipenem/betamipron once daily, which
      gives a similar clinical result in a patient with normal renal function.

PMID- 15729485
TI  - Clinical study of the effectiveness of imipenem/cilastatin sodium as the
      antibiotics of first choice in the expectant management of patients with preterm
      premature rupture of membranes.
AB  - We carried out a study to evaluate the effectiveness of imipenem/cilastatin
      sodium (IPM/CS) in the expectant management of patients with preterm premature
      rupture of membranes (PPROM). The study group (100 women) who presented with
      PPROM from 24 to 31 weeks of gestation, between 1997 and 1999, were managed
      expectantly, and received IPM/CS (plus betamethasone) as the antibiotics of first
      choice. The control group, 40 women, in 1995 and 1996, with PPROM at the same
      gestational age, were managed expectantly, but received neither these specific
      antibiotics (IPM/CS) nor betamethasone. The mean time from PPROM to delivery (11
      days) in the study group was longer that that (6 days) in the control group. No
      infant died within 1 year after birth in the study group, and five infants died
      during this period in the control group. We conclude that IPM/CS, combined with
      betamethasone, has potential as the antibiotics of first choice when employed for
      patients with PPROM.

PMID- 15729486
TI  - VapB-positive Rhodococcus equi infection in an HIV-infected patient in Japan.
AB  - Rhodococcus equi, a bacterium present in soil, is a common cause of pneumonia in
      foals. This organism has been recognized as an opportunistic pathogen in humans,
      typically causing infection in immunocompromised hosts such as HIV-infected
      patients and organ transplant recipients. However, human infection with R. equi
      has not been reported in Japan except in a case involving a laboratory worker. We
      report the first human case of VapB-positive R. equi pneumonia, which involved an
      HIV-infected patient living in an urban area in Japan. The patient was treated
      successfully with 450 mg rifampicin and 600 mg tosufloxacin, even though his CD4+
      lymphocyte count at the time of diagnosis was 10/microl. The patient's dogs were
      suspected in the epidemiology of this infection, but unfortunately we could not
      isolate the organism from canine-associated specimens in this case. R. equi
      infections in companion animals have been thought to be very rare, but they may
      be increasing in dogs. Therefore, further epidemiological research may clarify
      the prevalence of R. equi infection and the factors predisposing dogs to this
      infection.

PMID- 15729487
TI  - A side effect of neuraminidase inhibitor in a patient with liver cirrhosis.
AB  - Neuraminidase inhibitors have been widely used in Japan since 2001, and several
      side-effects of their use have been reported. However, erythema toxicum has
      rarely been described as a side-effect of these drugs in patients with liver
      function disorder. Here, we report a case of generalized rash after treatment
      with the neuraminidase inhibitors zanamivir and oseltamivir administered
      prophylactically to prevent influenza infection in two patients with hepatoma
      associated with liver cirrhosis.

PMID- 15729488
TI  - Survey of the susceptibility of urinary isolates to antibacterial agents in 2003.
AB  - In 2003, 826 uropathogenic strains were obtained from the urine of our patients.
      We assessed their activities to antibacterial agents based on the minimal
      inhibitory concentration (MIC) breakpoints recommended by the National Committee
      for Clinical Standards (NCCLS). Methicillin-resistant strains accounted for about
      70% of Staphylococcus aureus and Staphylococcus epidermidis. The most common gram
      positive species was Enterococcus faecalis (15.6%). Enterococcus faecium was the
      most resistant of the enterococcal species, and the rate of susceptibility to
      beta-lactams (BLs), fluoroquinolones (FQs), and tetracyclines (TCs) was 0%, 6%,
      and less than 18%, respectively. Escherichia coli accounted for over 50% of the
      gram-negative bacilli. The proportion of FQ-resistant or intermediate strains was
      over 20%, and four of these strains (1.1%) were suspected of producing extended
      spectrum beta-lactamase (ESBL). All the ESBL-producing strains (ESBLs) possess
      resistance to FQs. Over 95% of Klebsiella pneumoniae was susceptible to all
      agents. The distribution of antimicrobial activity against Pseudomonas aeruginosa
      indicated a decrease in the number of multidrug-resistant strains and an increase
      in strains susceptible to all agents. Some differences existed in the resistance
      to antibacterial agents among Proteus species. No ESBL-producing or multidrug
      resistant strain was isolated from Serratia marcescens. This survey suggests that
      serious clinical problems will result from the increasing number of enterococcal
      species with multidrug resistance in gram-positive cocci, and isolates of ESBL
      producing or FQs-resistant strains in gram-negative bacilli.

PMID- 15729489
TI  - Current status of antimicrobial susceptibility of clinical isolates of
      Streptococcus pyogenes in Japan: report of a countrywide surveillance study.
AB  - The growing number of macrolide-resistant strains of Streptococcus pyogenes is an
      increasing problem worldwide. In this study, we evaluated 62 clinical isolates of
      S. pyogenes obtained from the upper respiratory tract. Susceptibilities to
      penicillins, cephalosporins, fluoroquinolones, macrolides, and carbepenems were
      determined by minimal inhibitory concentrations (MICs). Expressions of macrolide
      resistance genes (mefA, ermB, and ermTR) were also examined, by polymerase chain
      reaction (PCR). All strains were susceptible to beta-lactams. On the other hand,
      of the 62 S. pyogenes isolates, 6.5%, 6.5%, 6.5%, and 3.2% of the strains were
      resistant to azithromycin (AZM), roxithromycin (RXM), clarithromycin (CAM), and
      telithromycin (TEL), respectively. Four (6.5%) strains had a type of macrolide
      resistance gene; there were two strains with ermB and two strains with ermTR, and
      these four strains were resistant to AZM, CAM (one strain was intermediately
      resistant), and RXM. Strains having ermB were resistant to TEL (MIC, > or = 8
      microg/ml), while strains having ermTR were susceptible to TEL. Physicians and
      researchers need to take into consideration the macrolide resistance of some
      strains of S. pyogenes.

PMID- 15729490
TI  - Clinical effect of intravenous ciprofloxacin on hospital-acquired pneumonia.
AB  - The effect of intravenous ciprofloxacin (CPFX) on hospital-acquired pneumonia was
      examined. The subjects were 32 patients with hospital-acquired pneumonia
      classified as being in group I, group II, and group III, based on The Japanese
      Respiratory Society Guidelines for management of hospital-acquired pneumonia.
      None of the patients had received antibiotic treatment for the pneumonia. CPFX
      300 mg was intravenously infused twice daily for 3-14 days, and its clinical
      effect, bacterological effect, and side effects were examined. Intravenous CPEX
      was clinically effective in 21 of the 32 patients, with an efficacy rate of
      65.6%. With regard to bacteriological efficacy, 4 of 5 strains of methicillin
      sensitive Staphylococcus aureus, 2 of 3 strains of Klebsiella pneumoniae, 1 of 2
      strains of Streptococcus pneumoniae, 1 of 2 strains of Streptococcus agalactiae,
      1 of 2 strains of Pseudomonas aeruginosa, 1 of 2 strains of Serratia marcescens,
      and the 1 strain of Klebsiella oxytoca were eradicated, with an eradication rate
      of 42.3% (11 of 26 strains whose fate was confirmed eradicated). Abnormal
      laboratory findings (side effects) were observed in 11 of the 32 patients
      (34.4%), but all side effects were mild. Based on the above data, intravenous
      CPFX may be the drug which should be recommended as the first choice for hospital
      acquired pneumonia.

PMID- 15729492
TI  - Antiepileptic medications in multiple sclerosis: adverse effects in a three-year
      follow-up study.
AB  - Neuropathic pain and paroxysmal symptoms are common in multiple sclerosis (MS)
      patients, although no double-blind clinical trial has been conducted to support
      antiepileptic medications (AED) use in MS. The aim of the study was to evaluate
      the frequency of AED utilisation and reported adverse events, in a cohort of MS
      patients. For a period of 3 years the rationale for prescribing AED, adverse
      effects, treatment duration and reasons for discontinuation were recorded in a
      database. Carbamazepine (CBZ) was prescribed in 36 patients, with adverse effects
      reported in 20 cases, of which 12 mimicked a relapse. Gabapentin (GBP) was
      prescribed in 94 patients, with adverse effects reported in 16 cases and in one
      case mimicked a relapse. Lamotrigine (LMT) was prescribed in 22 patients, with
      adverse effects reported in 4 cases, none mimicking a relapse. The present study
      found a significantly higher incidence of adverse effects in patients treated
      with CBZ, with a high rate of discontinuation at low dosages and episodes of
      evident worsening of neurological functioning compared to GBP or LMT.

PMID- 15729493
TI  - Cerebral venous thrombosis: a retrospective multicentre study of 48 patients.
AB  - The objective was to describe the clinical features and management of cerebral
      venous thrombosis (CVT) in non-selected centres. An observational study in 11
      neurological departments in NW Italy was carried out from 1995 through 1999 on 38
      female and 10 male patients. Mean age: 44.8 years, SD=14.3. Onset: acute in 21
      patients (44%), subacute in 17 (35%) and chronic in 10 (21%). Most frequent
      onset: with focal deficits and/or seizures, followed by impaired consciousness or
      confusion, isolated headache, isolated intracranial hypertension and cavernous
      syndrome. No risk factor was found in 8 patients (17%). The superior sagittal
      sinus was involved in 27 patients (56%) and the transverse sinus in 29 (60%).
      Anticoagulants were used in 45 patients (94%). Rankin Scale score at discharge: 0
      (27 patients), 1 (four), 2 (five), 3 (five), 4 (none), 5 (one) and six were dead.
      Thirteen patients had deep CVT: age, risk factors, neurological signs and outcome
      differed from cortical CVT (35 patients), although not significantly. Clinical
      features, risk factors and outcome of CVT patients from non-selected centres are
      similar to those from specialised centres.

PMID- 15729494
TI  - REM sleep behaviour disorder in Parkinson's disease: a questionnaire-based study.
AB  - The aim of the study was to determine the clinical frequency and features of REM
      sleep behaviour disorder (RBD) in a large population of Parkinson's disease (PD)
      patients using defined diagnostic criteria both for RBD and PD. Six trained
      neurologists used a semistructured questionnaire based on ICSD-R diagnostic
      criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver
      reliability for the diagnosis of RBD was "substantial" (Kappa 0.65). Five
      patients were excluded from the study because of an MMSE lower than 25. The
      demographic and PD clinical features were compared in the clinically defined RBD
      group and in those without RBD (NRBD). Then the RBD features during the last year
      were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R
      criteria for RBD; 62 patients reported RBD during the last year (frequency
      31.8%). RBD features: two or more episodes per week in 35.5%; upper limb
      movements in 87%; lower limb movements in 79%; vocalisations during events in
      85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured
      themselves or their caregivers during sleep. According to multivariate analysis,
      RBD was associated with male gender, age and PD duration. Brief training and the
      use of a semistructured questionnaire may help the neurologist in dealing with
      sleep disturbances in PD patients. The search for RBD symptoms in PD is highly
      recommended, especially in patients with a long disease duration, the risk of
      sleep-related injuries being high.

PMID- 15729495
TI  - Interpretation of a complex picture and its sensitivity to frontal damage: a
      reappraisal.
AB  - A. R. Luria introduced the interpretation of a meaningful picture as a tool for
      assessing pre-frontal impairment. We gave this test to 196 normal adults, who
      were asked to communicate what was happening in the portrayed scene (a boy chases
      a mouse hidden under a cupboard, while three frightened girls assist). The same
      subjects were given two other frontal tests (verbal fluency on phonemic cue and
      Trail Making Test (TMT)) and Raven's Matrices. Twenty-three normal subjects (12%)
      failed to correctly interpret the picture. We also examined 20 patients whose
      brain lesion encroached upon pre-frontal areas, in order to check if this version
      of the test could be easily administered to this type of patient, and if its
      difficulty level was appropriate for avoiding ceiling and floor effects. Twelve
      patients were unable to interpret the picture (60%). A similar failure rate was
      observed with the same subjects on verbal fluency and TMT, while Raven's Matrices
      were less impaired (35%). Some dissociation was found between Picture
      Interpretation and the TMT. The Italian version of the Picture Interpretation
      Test is suitable for the examination of pre-frontal patients.

PMID- 15729496
TI  - Myasthenia gravis self-administered questionnaire: development of regional
      domains.
AB  - The objective was to develop regional domains from the Myasthenia Gravis
      Questionnaire (MGQ) to better assess generalised, bulbar and ocular involvement
      in patients with myasthenia gravis (MG) and to evaluate their responsiveness.
      Some items from the MGQ were aggregated into 3 domains: bulbar, generalised and
      ocular. The study was carried out at the Institute of Neurology, EMG Service,
      Universita Cattolica, Rome, and the Department of Neurology, University Hospital,
      Modena, Italy. Ninety-three MG patients were prospectively enrolled in two
      neurological departments; furthermore, outcome after treatment was studied in 23
      patients to evaluate responsiveness. Disease severity was scored according to a
      modified version of the Osserman classification and MGQ. The questionnaire
      appeared more sensitive than clinical examination and history to assess bulbar
      and ocular involvement. For example, according to the bulbar domain, 67 patients
      experienced bulbar symptoms whereas on clinical examination 51 of 67 were
      completely normal in the bulbar region. The MGQ domains appeared reliable and
      sensitive. Results of global MG score (GMG) and of domains appeared reliable.
      Domains were able to better assess the functional involvement of anatomical
      regions than main GMG, clinical examination and history.

PMID- 15729497
TI  - Magnesium as a treatment for paediatric tension-type headache: a clinical
      replication series.
AB  - The objective was to determine the initial utility of magnesium salt as a
      treatment for paediatric episodic and chronic tension-type headache (TTH). The
      study took the form of a clinical replication series in the Outpatient Headache
      Center at the National Neurological Institute "C. Besta", Milan, Italy. The
      patients were five children/adolescents with episodic and four with chronic TTH
      reporting consecutively for treatment. Magnesium pidolate (2.25 g) was given
      twice per day for two months, with one year of follow-up. No other treatment was
      provided. Patients with episodic TTH revealed 76.0% symptom reduction, with 80%
      of the sample achieving reductions greater than 50%. The patients with chronic
      TTH revealed 87.5% symptom reduction, with 100% of the sample achieving
      reductions greater than 50%. Analgesic consumption decreased significantly for
      chronic TTH. Only one child took medication in the episodic TTH group. No
      significant changes occurred with respect to depression and anxiety, but these
      measures were not clinically elevated at the start of treatment. Although
      uncontrolled, the initial findings are encouraging and suggest that further,
      better controlled research is warranted.

PMID- 15729498
TI  - Sudden re-opening of collapsed transverse sinuses and longstanding clinical
      remission after a single lumbar puncture in a case of idiopathic intracranial
      hypertension. Pathogenetic implications.
AB  - The aetiopathogenetic role of sinus venous obstructions carried by most
      idiopathic intracranial hypertension (IIH) patients is controversial. We report
      the case of a young woman diagnosed with IIH with papilloedema and narrowing of
      transverse sinuses, in which lowering of intracranial pressure by a single 20 ml
      cerebrospinal fluid (CSF) resulted in a strong dimensional increase of the
      transverse sinuses. Changes were followed by clinical remission and normalisation
      of optical nerve calibre, maintained after a 2-month follow-up. Our findings
      indicate that, although secondary to CSF hypertension, venous sinuses compression
      may have an important role in hypertensive status maintenance. Pathogenetic
      implications of venous sinus compression by hypertensive CSF in IIH are
      discussed.

PMID- 15729499
TI  - Meningeal carcinomatosis causing isolated bilateral symmetric progressive hearing
      loss.
AB  - A 53-year-old man presented with isolated bilateral progressive hearing loss from
      about 5 months. Fourteen months after onset of this isolated symptom a diagnosis
      of meningeal carcinomatosis (MC) was made. Isolated bilateral deafness is a rare
      first manifestation of MC.

PMID- 15729500
TI  - Chronic subdural haematoma complicating spinal anaesthesia.
AB  - Cranial subdural haematoma formation following spinal anaesthesia is
      exceptionally rare. A 38-year-old male developed headache two days after
      testicular surgery under spinal anaesthesia. The headache progressed in spite of
      analgesics, and three weeks later cranial CT showed a large chronic subdural
      haematoma in the left fronto-parietal region. The patient improved after surgical
      decompression. The pathogenesis of subdural haematoma formation after dural
      puncture is discussed and the literature briefly reviewed. Prolonged and severe
      post-dural puncture headache should be viewed with suspicion and investigated
      promptly to rule out any intracranial complication.

PMID- 15729501
TI  - The limits of scientific research.

PMID- 15729503
TI  - Thermodynamics of membrane elasticity--a molecular level approach to one- and two
      component fluid amphiphilic membranes, part I: theory.
AB  - The present publication provides a detailed theoretical approach to the elastic
      properties of one- and two-component amphiphilic membranes. It is formulated in
      terms of the molecular free energy aiming at an application to molecular models.
      The work focuses on the bending elastic moduli and the difference between the
      condition of constant surface tension and constant chemical potentials. It is
      found that the bending modulus of mean curvature becomes negative for two
      component membranes approaching the limit of phase separation at constant
      chemical potentials. The treatment of bilayer membranes explicitly integrates
      monolayer-monolayer coupling. This is beneficial for the assessment of coupling
      effects for specific molecular models. The article is completed by a
      comprehensive continuum mechanical description of one-component monolayers. Based
      on the generalized Laplace equation it is suggested that a simultaneous excess of
      oil and water is likely to preclude the existence of non-cylindrical bicontinuous
      phases.

PMID- 15729505
TI  - Structure of polymer micelles close to the solid interface. A grazing incidence
      small angle neutron scattering study.
AB  - Block copolymers are widely used in industry. For scientific interests their
      aqueous solutions offer a model system for the investigation of crystallisation
      as the macromolecules agglomerate for elevated concentrations into micelles,
      which crystallise when a critical volume fraction is reached. We report on
      grazing incidence small angle neutron scattering (GISANS) or near surface small
      angle neutron scattering (NS-SANS) as an experimental tool to investigate the
      micelle crystallisation close to interfaces with different chemical termination.
      We find that in general crystallization is suppressed at a repulsive surface and
      favoured at an attractive one. Furthermore we show that the crystallization close
      the interface can be controlled by the micelle stability, resulting from the
      different composition and length of the monomers. The effect of the interface is
      found more important for a high micelle stability, whereas for a low stability it
      is shadowed by adsorbed monomers.

PMID- 15729504
TI  - Thermodynamics of membrane elasticity--a molecular level approach to one- and two
      component fluid amphiphilic membranes, part II: applications.
AB  - The theoretical framework developed in the accompanying publication is applied to
      a number of experimentally relevant amphiphilic systems. These include the
      influence of thermodynamic conditions and non-ideal mixing on bending elasticity,
      ellipsoidal modes of microemulsions and vesicles, hydrocarbon chain coupling in
      bilayers and the effect of osmotic and hydrostatic pressure on inverse hexagonal
      (H(II)) phases. It is found that the bending moduli at constant surface tension
      and constant chemical potentials are markedly different only for two-component
      membranes and non-ideal mixing with a tendency towards phase separation. The
      results indicate that non-ideal mixing is the main reason behind the
      experimentally observed strong compositional dependence of membrane elasticity.
      It is generally recommended to prefer the bending elastic moduli at constant
      chemical potentials to those at constant surface tension. A comparison between
      the area-difference-elasticity (ADE) model and explicit free energy calculations
      using a molecular model shows a good qualitative agreement for the sphere-to
      ellipsoid transition of vesicles. Results for different free energy models of the
      hydrocarbon chains of amphiphilic molecules suggest that monolayer-monolayer
      chain coupling is responsible for the relatively higher bending stiffness of
      bilayers compared to single monolayers. For H(II)-phases an instability at
      negative pressure differences is predicted.

PMID- 15729506
TI  - Viscoelasticity of a protein monolayer from anisotropic surface pressure
      measurements.
AB  - We present a method to completely characterize the viscoelasticity of Langmuir
      monolayers. In contrast to existing techniques, both the compression and shear
      moduli are determined at the same time, in a single experiment and with a
      standard apparatus. This approach relies on the measurement of anisotropy in the
      surface pressure: the tension is measured in orientations perpendicular and
      parallel to the compression direction. We apply this technique to the study of
      beta-lactoglobulin spread monolayers, a system that has been shown to develop a
      shear modulus at high concentration. Beta-lactoglobulin monolayers are
      interesting both because of their importance in food science and because they
      exhibit universally slow dynamical behavior that is not fully understood. Our
      results confirm that the compressional modulus dominates the total viscoelastic
      response and also provide a complex shear modulus, emerging above a critical
      concentration. We are able to describe how each of the dynamical response moduli
      is related to the surface concentration and to the equilibrium osmotic pressure.

PMID- 15729507
TI  - Anchoring and structural transitions as a function of molecular length in
      confined liquid crystals.
AB  - Using deuteron nuclear magnetic resonance to study liquid crystals confined to
      cylindrical pores, an anchoring transition has been found. The transition
      exhibits an unexpected sharp dependence of the anchoring strength on
      cyanobiphenyl liquid crystal molecular length. A structural transition from a
      parallel axial to a planar radial configuration occurs due to an anchoring
      transition from planar to weakly homeotropic orientation at the walls. The
      anchoring strength is at a minimum near the decylcyanobiphenyl (10CB) liquid
      crystal length. Long chain liquid crystal configurations depend on thermal
      cycling and on the equilibrium atmosphere leading to a bistable SmA structure.
      Orientational order wetting in the isotropic phase also depends on molecular
      length.

PMID- 15729508
TI  - Molecular multivalent electrolytes: microstructure and screening lengths.
AB  - We study small rod-like molecular electrolytes solutions with their corresponding
      atomic counterions. The asymptotic length scales (decay length and wavelength) of
      the structural correlations are analyzed using the formalism of the dressed
      interaction site theory (DIST). The correlation functions are determined using
      the reference interaction site model equation complemented with a mixed approach
      in which the hypernetted-chain closure is used for the repulsive interactions,
      and the mean spherical approximation is used for the attractive interactions. The
      results from this scheme are in good agreement with the Monte Carlo computer
      simulations reported here. The asymptotic properties of the correlation functions
      of this molecular system are compared against those corresponding to two related
      simple (atomic) electrolyte models. The main conclusion is that the molecular
      structure of the ions lowers by two orders of magnitude the concentration at
      which the transition from monotonic to oscillatory decay occurs.

PMID- 15729509
TI  - Selective imaging of 3D director fields and study of defects in biaxial smectic A
      liquid crystals.
AB  - We report on the selective imaging of different director fields in a biaxial
      smectic A (SmAb) liquid crystal using Fluorescence Confocal Polarizing Microscopy
      (FCPM) and Polarizing Microscopy (PM). The patterns of two directors, namely the
      director n(a) perpendicular to the lamellae and the director n(b) in their planes
      are visualized by doping the liquid crystal with two fluorescent dyes with
      different orientation of the transition dipoles with respect to the lamellar
      matrix. The properties of defects such as disclinations and focal conic domains
      (FCDs) are consistent with the non-polar D2h-symmetry of the SmA(b) mesophase in
      the studied mixture of bent-core and rod-like molecules: (1) majority of defects
      in the director n(b) are half-integer "+/-1/2" disclinations; (2) the integer
      strength "+/-1" defects tend to split into the "+/-1/2" disclinations. We compare
      the vertical cross-sections of the "+/-1" disclinations in the field in SmA(b)
      and uniaxial nematic samples. In SmA(b), the "+/-1" disclinations do not escape
      into the third dimension, while in the nematic samples with Schlieren textures
      they do despite the surface anchoring at the plates; the experimentally
      determined director field around the escaped disclination capped by a pair of
      surface point defects--boojums matches the one predicted recently [C. Chiccoli et
      al., Phys. Rev. E 66, 030701 (2002)]. The FCD structure in SmA(b) is similar to
      that in SmA and SmC in terms of the normal to the layers but differs
      significantly in terms of the director n(b) field parallel to the smectic layers.
      The FCDs in SmA(b) can be associated with topologically non-trivial
      configurations of n(b) in the surrounding matrix that are equivalent to the
      disclination lines.

PMID- 15729510
TI  - Behavior of the layer compression elastic modulus near, above, and below a
      smectic C-hexatic I critical point in binary mixtures.
AB  - We present the first study of the layer compression modulus B carried out near,
      above and below the Smectic C-Hexatic I critical point in racemic mixtures of
      methylbutyl phenyl octylbiphenyl-carboxylate (8SI) and the octyloxy biphenyl
      analog (8OSI), at frequencies ranging from 0.2 Hz to 2 x 10(3) Hz. The behavior
      of B as a function of temperature shows a progressive evolution from a first
      order transition in 8SI to a continuous supercritical behavior in 8OSI. The
      latter is characterized by an increase in B, which appears above the transition,
      and which is followed by a leveling off when the temperature is decreased towards
      the transition. It is proposed that this behavior stems from the relaxation of
      the hexatic domains which are frozen in the frequency range studied. For the
      supercritical and near-critical compounds, B exhibits a small dip near the
      transition temperature, which is visible in the low frequency range only,
      indicating that the dynamics associated with the critical point is very slow. We
      also report measurements in the Crystal-J phase of the pure compounds, and show
      that 8SI behaves mechanically as a hexatic phase and 8OSI as a soft crystal
      phase.

PMID- 15729511
TI  - Predicting the mechanical properties of spider silk as a model nanostructured
      polymer.
AB  - Spider silk is attractive because it is strong and tough. Moreover, an enormous
      range of mechanical properties can be achieved with only small changes in
      chemical structure. Our research shows that the full range of thermo-mechanical
      properties of silk fibres can be predicted from mean field theory for polymers in
      terms of chemical composition and the degree of order in the polymer structure.
      Thus, we can demonstrate an inherent simplicity at a macromolecular level in the
      design principles of natural materials. This surprising observation allows in
      depth comparison of natural with man-made materials.

PMID- 15729512
TI  - Crystallization of a poly(ethylene-co-octene): I. A precursor structure and two
      competing mechanisms.
AB  - Observations of a sample of poly(ethylene-co-octene)in a polarizing optical
      microscope reveal peculiarities in its crystallization behavior. When cooled from
      the melt to a fixed crystallization temperature, at first a structure of diffuse
      appearance with variations on the length scale of micrometers forms rapidly. The
      transformation into the final semi-crystalline state then proceeds in two ways,
      by a continuous change of the inner structure of microm-sized objects and by the
      growth of spherulites. Time dependent small angle and wide angle X-ray scattering
      experiments corroborate the occurrence of the two crystallization mechanisms.
      Atomic force microscopy indicates that the change of the inner structure of the
      preformed objects is due to an in-filling of crystallites.

PMID- 15729513
TI  - Crystallization of poly(ethylene-co-octene): II. Melt memory effects on first
      order kinetics.
AB  - Dilatometric and X-ray scattering experiments of the crystallization kinetics of
      a sample of poly(ethylene-co-octene) show pronounced melt memory effects, i.e.,
      the shapes of isotherms and characteristic times vary systematically with the
      temperature of the melt prior to cooling to the crystallization temperature. The
      temperature range of the effect is limited; crystallization kinetics remains
      constant below a melt temperature T(m)l and above a melt temperature T(m)h and
      varies only in-between. Analysis shows that the melt memory effect is caused by a
      variation of the characteristic time of a first order crystallization process.
      The process can be assigned to the in-filling of crystallites into objects of a
      previously generated precursor structure.

PMID- 15729514
TI  - Depletion interactions between two spherocylinders.
AB  - The depletion interactions between two spherocylinders as functions of their
      separation and their relative orientation, induced by a small hard-sphere fluid,
      are calculated by Monte Carlo simulations using the acceptance ratio method
      (ARM). The torque on the spherocylinders is determined from the resulting
      potential. The calculation shows that the ARM is an effective way to obtain
      depletion interactions of spherocylinders. The depletion interaction under the
      Asakura-Oosawa (also excluded-volume) approximation is also calculated
      numerically.

PMID- 15729515
TI  - Medical therapy of epilepsy: when to initiate treatment and when to combine?
AB  - Most patients reporting more than one well-documented or witnessed seizure
      require prophylactic antiepileptic (AED) therapy. Those with an underlying brain
      disorder and/or an abnormal electroencephalogram should probably be treated after
      their first event. The goal should be maintenance of a normal lifestyle by
      complete seizure control with no or minimal side-effects. Failure of the first
      AED due to lack of efficacy implies refractoriness. A policy of consecutive
      substitutions is unlikely to be an effective strategy. Thus, if the first or
      second monotherapy improves control but does not produce seizure freedom, an AED
      with different and perhaps multiple mechanisms of action should be added.
      Strategies for combining drugs should involve individual assessment of patient
      related factors, including seizure type and epilepsy syndrome classifications
      coupled with an understanding of the pharmacology, side-effects and interaction
      profile of the AEDs. Reducing the dose of one or more AEDs may help accommodate
      the introduction of a second or third drug. An orderly approach to the
      pharmacological management and, when appropriate, surgical investigations for
      each epilepsy syndrome will optimise the chance of perfect seizure control and
      help more people achieve safer and more fulfilled lives.

PMID- 15729516
TI  - Complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) may develop after limb trauma and is
      characterized by pain, sensory-motor and autonomic symptoms. Most important for
      the understanding of the pathophysiology of CRPS are recent results of
      neurophysiological research. Major mechanism for CRPS symptoms, which might be
      present subsequently or in parallel during the course of CRPS, are trauma-related
      cytokine release, exaggerated neurogenic inflammation, sympathetically maintained
      pain and cortical reorganisation in response to chronic pain (neuroplasticity).
      The recognition of these mechanisms in individual CRPS patients is the
      prerequisite for a mechanism-oriented treatment.

PMID- 15729517
TI  - Parkinsonism with excessive daytime sleepiness--a narcolepsy-like disorder?
AB  - BACKGROUND: Parkinsonian patients with excessive daytime sleepiness (EDS),
      hallucinations, REM sleep behavior disorder (RBD), short mean sleep latencies,
      and sleep-onset REM periods (SOREMP) on multiple sleep latency tests (MSLT) have
      been reported. In these patients a narcolepsy-like pathophysiology of sleep-wake
      disturbances has been suggested. PATIENTS AND METHODS: We studied 14 consecutive
      patients with Parkinsonism and EDS. Standard studies included assessment of
      duration and severity of Parkinsonism (Hoehn & Yahr score), Epworth sleepiness
      score (ESS), history of "REM-symptoms" (RBD/hallucinations/sleep
      paralysis/cataplexy-like episodes), polysomnography (PSG), MSLT, and measurement
      of cerebrospinal fluid (CSF) levels of hypocretin-1 (orexin A). RESULTS: There
      were 12 men and 2 women (mean age 69 years; range 54-82). The mean duration and
      the Hoehn&Yahr score were 6.3 years and 2.2, respectively. Diagnoses included
      idiopathic Parkinson's disease (IPD, n = 10), dementia with diffuse Lewy bodies
      (n = 3), and multisystem atrophy (n = 1). The ESS was > or = 10 in all patients
      (mean 12; range 10-18). "REM-symptoms" were reported by all but two patients
      (hallucinations: n = 9; RBD: n = 9). None of the patients reported cataplexy-like
      symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n =
      7), periodic limb movements during sleep (PLMS-index > 10/h, n = 6), and features
      of RBD (n = 5) were found. On MSLT mean sleep latency was < 5 minutes in 10
      patients, and SOREMP were found in two patients. When compared with controls (n =
      20, mean 497 pg/ml; range 350-603), CSF hypocretin-1 levels were normal in 8
      patients and low in 2 patients (221 and 307 pg/ml, respectively). CONCLUSION:
      These findings do not support the hypothesis of a "final common pathway" in the
      pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep apnea and PLMS may
      play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian
      patients.

PMID- 15729518
TI  - Intrathecal sICAM-1 production in multiple sclerosis--correlation with triple
      dose Gd-DTPA MRI enhancement and IgG index.
AB  - In this study the aim was to evaluate the intrathecal sICAM-1 production in
      multiple sclerosis (MS) patients during relapse and remission. In addition to
      this, we assessed whether there is a correlation between intrathecal sICAM-1
      production and other disease activity markers such as IgG index and gadolinium
      enhancement in magnetic resonance imaging (MRI). Twenty four relapsing-remitting
      MS patients were included in the study. Serum and cerebrospinal fluid (CSF)
      samples were obtained both during relapse and remission. The soluble form of ICAM
      (sICAM) was measured by the ELISA method in serum and CSF. Cranial MRI with
      triple dose gadolinium injection was performed for each patient both during
      relapse and remission. Serum levels of sICAM-1 (245.23 +/- 92.88 ng/ml) were
      higher during relapse than those in remission (219.90 +/- 110.94 ng/ml), but the
      difference was not statistically significant. In relapse periods CSF levels of
      sICAM-1 (1.304 +/- 0.92 ng/ml) were higher than those in remission (1.06 +/- 0.86
      ng/ml), but this was not significant. However, during relapse periods patients
      had significantly higher sICAM-1 index values (1.76 +/- 0.60) than those found
      during remission periods (1.01 +/- 0.44) (p < 0.05). The IgG index values were
      higher in relapse periods than in remission (0.88 +/- 0.37 vs. 0.67 +/- 0.28) (p
      < 0.005). On T1 weighted images following triple dose Gd injection, at least two
      or more enhancing lesions were present in 22/24 of the patients (91%) in relapse
      and 4/24 of the patients (19%) in remission. There was strong correlation both
      between the sICAM-1 index and Gd enhancement (r =0 .72 p < 0.05) and sICAM-1
      index and IgG index in relapse (r = 0.69 p < 0.05). In conclusion, there is
      association between high sICAM-1 and IgG indices, as well as between high sICAM-1
      index and Gd enhancing MRI lesions in relapsing MS patients.

PMID- 15729519
TI  - Median nerve motor conduction velocity is concordant with myelin protein zero
      gene mutation.
AB  - BACKGROUND: Myelin protein zero gene (MPZ) mutations may account for a small
      proportion of cases of Charcot-Marie-Tooth disease (CMT). Different MPZ mutations
      may be associated with different clinical and electrophysiological phenotypes.
      OBJECTIVES: To expand our understanding of the characteristics of nerve
      conduction velocity (NCV) in patients with different MPZ mutations, the authors
      collected and analysed the NCV values from patients with MPZ mutations. MATERIALS
      AND METHODS: The NCVs of fourteen patients from six families carrying MPZ
      mutations of Val58Asp, Ser63Phe, Thr65Ile,Arg98Cys, Arg98His, and Ser233fs were
      collected retrospectively. Five of them had received nerve conduction studies
      (NCS) twice. The mutations were verified by polymerase chain reaction (PCR)
      amplifications and nucleotide sequencing. Scatterplot analyses of median motor
      NCV (MNCV) versus specific MPZ mutation were performed. RESULTS: The median MNCV
      varied widely, with a mean of 16.3 m/s (SD = 7.7 m/s) and a range of 5.1-32.9
      m/s. Median MNCVs of patients with particular MPZ mutations were similar.
      Moreover, Median MNCV did not change significantly over time. CONCLUSIONS: There
      was concordance between median MNCV and specific MPZ mutations. However, median
      MNCV is not an ideal measure with which to distinguish CMT1B patients with MPZ
      mutations from CMT1A patients with PMP22 mutations.

PMID- 15729520
TI  - Clinical study of 99 patients with pure sensory stroke.
AB  - OBJECTIVE: We report a clinical description of pure sensory stroke based on data
      collected from a prospective acute stroke registry. METHODS: From 2500 acute
      stroke patients included in a hospital-based prospective stroke registry over a
      12-year period, 99 were identified as having pure sensory stroke. RESULTS: Pure
      sensory stroke accounted for 4.7% of all acute stroke patients, 5.4% of acute
      ischemic stroke, and 17.4% of lacunar syndromes. Complete hemisensory syndrome
      was present in 80 patients and incomplete hemisensory syndrome in 19 (cheiro-oral
      syndrome 12, cheiro-oral-pedal 6, isolated oral syndrome 1). The lacunar
      hypothesis was fulfilled in 88% of patients. Atherothrombotic infarction occurred
      in 8 patients, intracerebral hemorrhage in 3, and stroke of undetermined cause in
      1. Hemorrhagic pure sensory stroke was diagnosed in 1% of all cases of
      hemorrhagic stroke (n = 270) in the database. Outcome was good (in-hospital
      mortality 0%, symptom-free at discharge 41.5%). After multivariate analysis,
      absence of disability at discharge, hypertension, diabetes, hyperlipidemia, and
      thalamic (56.5%) and corona radiata (4%) locations were clinical and topographic
      variables significantly associated with pure sensory stroke. CONCLUSIONS: Pure
      sensory stroke is an infrequent cerebrovascular syndrome, in which the lacunar
      hypothesis is supported. Most patients had thalamic lacunar infarction.
      Incomplete hemisensory syndromes were also caused by a lacunar infarct in 84% of
      patients. Hemorrhagic pure sensory stroke accounted only for 3% of the cases. The
      prognosis is good with striking similarity to other lacunar strokes. There are
      important differences between pure sensory stroke and nonlacunar strokes.

PMID- 15729521
TI  - Cerebrovascular reactivity and dynamic autoregulation in nondemented patients
      with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy).
AB  - Reduced cerebrovascular reactivity has been reported in patients with cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL), and the measurement has been suggested as a useful surrogate marker of
      disease progression. Previous studies have not determined whether cerebral
      autoregulation is also impaired. We measured dynamic cerebral autoregulation and
      carbon dioxide reactivity in 24 nondemented CADASIL patients and 20 controls,
      using transcranial Doppler ultrasound (TCD). No impairment in either measure was
      found in the CADASIL group. We conclude that either cerebrovascular reactivity
      and autoregulation are not impaired in early disease, or that TCD may not be a
      sufficiently sensitive tool to detect haemodynamic changes in early disease. TCD
      is unlikely to be useful for disease monitoring in patients without advanced
      disease.

PMID- 15729522
TI  - Self-awareness after acquired brain injury--predictors and rehabilitation.
AB  - OBJECTIVE: To investigate the factors contributing to deficit in self-awareness
      following acquired brain injury and to study change in self-awareness during a
      group support program. METHODS: Sixty-two patients (mean age: 35.4 +/- 15.3
      years) attending our Service (295 +/- 525 days after injury) were included in the
      study (41 of them had sustained a head injury). Thirty-six patients were admitted
      to a multidisciplinary rehabilitation program including a group support program
      designed to improve self-awareness deficits. All patients were assessed with the
      Patient Competency Rating Scale as a measure of self-awareness and with a broad
      range of neuropsychological tests, checklists of psychopathological symptoms, and
      several functional scales. RESULTS: Thirty patients showed high levels of self
      awareness while 32 showed impaired self-awareness. Patients with appropriate
      perception of their deficits showed less psychopathological symptoms, better
      neuropsychological function and higher functional independence than those with
      impaired SA (Student's t test, p < 0.05). Both groups improved, but with
      different patterns, after rehabilitation (MANOVA, p < 0.05). Multiple regression
      analysis revealed that cognitive status was predictive of level of self
      awareness. CONCLUSION: The level of self-awareness after acquired brain injury is
      a useful prognostic index of the neuropsychological, psychopathological and
      functional status of the patient. We recommend the evaluation of this symptom
      after acquired brain injury due to its clinical relevance.

PMID- 15729523
TI  - Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD--a
      comparison of neuropsychological effects.
AB  - OBJECTIVE: To compare the cognitive and behavioural effects of unilateral
      pallidotomy and bilateral subthalamic nucleus (STN) stimulation. METHODS: After
      baseline examination 34 patients were randomly assigned to unilateral pallidotomy
      (4 left-sided, 10 right-sided) or bilateral STN stimulation (n = 20). At baseline
      and six and twelve months after surgery we administered neuropsychological tests
      of language, memory, visuospatial function, mental speed and executive functions.
      Also a depression rating scale, and self and proxy ratings of memory and
      dysexecutive symptoms were administered. RESULTS: Six months after surgery, the
      STN group and the pallidotomy group differed significantly in change from
      baseline in number of errors on two tests of executive functioning. After 12
      months the STN group reported less positive affect compared with baseline than
      the pallidotomy group. One patient in the STN group showed an overall cognitive
      deterioration due to complications. CONCLUSIONS: Although we need larger groups
      to draw firm conclusions, our results suggest that bilateral STN stimulation has
      slightly more negative effects on executive functioning than unilateral
      pallidotomy.

PMID- 15729524
TI  - Cognitive deficits and changes in neurometabolites after a lacunar infarct.
AB  - In contrast to earlier observations, recent studies have demonstrated that
      supratentorial lacunar infarcts in the white matter may cause mild
      neuropsychological impairments. The origin of these cognitive disturbances is yet
      unknown. In the current study proton magnetic resonance spectroscopy (1H MRS) was
      used to elucidate the hypothesized relation between a lacunar infarct, metabolic
      alterations, and neuropsychological function. Patients with a single
      supratentorial lacunar infarct (n = 26) were compared with patients with a mild
      myocardial infarct (n = 12) and healthy controls (n = 12) on a comprehensive
      neuropsychological examination, and on the N-acetyl-aspartate/creatine,
      choline/creatine and lactate/creatine ratios. The volume of interest of the
      MRI/MRS examination was located in normal-appearing white matter of the centrum
      semiovale at a distance from the infarct, in both the ipsilateral and
      contralateral hemisphere. On neuropsychological examination patients with a
      lacunar infarct performed worse than both patients with a myocardial infarct and
      healthy controls. The N-acetyl-aspartate/creatine ratio was decreased in patients
      with a lacunar infarct compared with the other two groups. More important, this
      decrease in neurometabolites was significantly correlated to the level of
      cognitive functioning for the ipsilateral hemisphere and, although to a lesser
      extent, for the contralateral hemisphere. We conclude that a single symptomatic
      lacunar infarct in the white matter is associated with (distant) disturbances in
      neurometabolites and that this decrease is related to a reduced cognitive
      capacity.

PMID- 15729527
TI  - Cognitive evaluation in adult patients with Mobius syndrome.
AB  - OBJECTIVE: To establish the occurrence of mental retardation in a group of
      patients with Mobius syndrome and subsequently, if mental retardation is absent,
      to screen major aspects of memory and attention, in order to assess possible
      pervasive dysfunction in these cognitive domains which might be responsible for
      the current view that mental retardation occurs frequently in Mobius syndrome.
      METHODS: In a group of 12 Dutch Mobius patients, intellectual performance, memory
      function and attention were assessed using a number of standardized
      neuropsychological tests. RESULTS: The mean general intellectual performance did
      not differ significantly from that of the Dutch population. Screening of
      selective attention and memory did not provide indications of pervasive
      dysfunctions in these domains. CONCLUSION: The rate of occurrence of mental
      retardation in our group of Mobius patients did not differ from that in the
      normal Dutch population. Furthermore, there was no evidence of attention and
      memory dysfunction in our group of Mobius patients.

PMID- 15729526
TI  - Strategies in detection of the primary tumour in anti-Yo associated
      paraneoplastic cerebellar degeneration.
AB  - In patients with anti-Yo associated paraneoplastic cerebellar degeneration (PCD)
      neurological symptoms precede the diagnosis of the underlying cancer in about
      60%. Ovarian carcinoma, breast cancer and other gynaecological malignancies are
      most frequently found as causative malignancies. Antitumour treatment should be
      applied in an early stage of disease. The identification of the tumour is a
      diagnostic challenge in many of these patients. In the first of two patients
      reported here a pelvic tumour was suggested after detection of a pathological
      lymph node and elevated tumour markers. The intraoperative findings appeared
      macroscopically normal during ovariectomy with adnexectomy. Not until microscopic
      examination of the resected tissue was performed was a tubal adenocarcinoma
      found. If intrapelvic gynaecological tumours are suspected a deliberate surgical
      exploration seems to be justified, but only after an intensive diagnostic
      investigation. To search for the underlying cancer in patients with
      paraneoplastic neurological disorders successive CT and [18F]-FDG-PET are widely
      recommended. Instead of this in the second reported patient whole-body dual
      modality PET/CT was performed revealing enhanced uptake in three regions of the
      left thorax. By combining function and anatomy PET/CT was able to localise the
      lesions and characterise them as lymph node metastases of breast cancer.
      Diagnosis could be confirmed by subsequently executed needle biopsy. PET/CT seems
      to be highly applicable in the investigation of paraneoplastic disorders with
      unknown primary cancer. It may help in guidance of needle biopsy or to optimise
      the results of deliberate surgery and it provides whole-body tumour staging in a
      single session with higher diagnostic accuracy than PET alone.

PMID- 15729525
TI  - Angiotensin I converting enzyme polymorphism effects in patients with normal
      pressure hydrocephalus syndrome before and after surgery.
AB  - Previous reports have suggested an association between the insertion/deletion
      (I/D) polymorphism of the angiotensin-converting enzyme (ACE), cardiovascular
      disease, and cognitive performance. Normal pressure hydrocephalus (NPH) is
      considered to be an example of reversible dementia although the clinical
      improvement after shunting varies from subject to subject. An association has
      been suggested between vascular risk factors and the development of NPH. The ACE
      plays a major role in vascular pathology and physiology. In the present study we
      investigated the distribution of an ACE gene insertion/deletion polymorphism in
      112 patients diagnosed with NPH and in 124 controls. We also evaluated the role
      of this genetic polymorphism in cognitive functioning before and following
      surgery in a subgroup of 72 patients. No differences in genetic or allele
      distributions were found between patients and healthy subjects, but among
      patients, carriers of D/D or D/I genotypes obtained less cognitive benefit
      following shunt surgery, especially on measures of memory and frontal function.
      Our data support previous findings in other conditions indicating that possession
      of at least one D allele is associated with poorer cognitive performance.

PMID- 15729528
TI  - High frequency stimulation of the subthalamic nucleus is efficacious in Parkin
      disease.
AB  - High frequency stimulation (HFS) of the subthalamic nucleus (STN) is an
      efficacious symptomatic treatment for Parkinson's disease. We have analysed the
      genetic status of a series of consecutive parkinsonian patients implanted for STN
      HFS and compared the outcome of five carrying mutations in the parkin gene with
      that of the non-parkin group. All patients obtained sustained control of PD
      symptoms and achieved functional improvement; in the parkin group the UPDRS motor
      score improved by 56.4%, the levodopa equivalent daily dosage was reduced by
      75.5%. Postoperative medications were reduced more in parkin than in non-parkin
      patients. We confirm that the current inclusion criteria for STN HFS do not
      exclude patients carrying mutations in the parkin gene; their clinical outcome is
      comparable to that of the non-parkin group.

PMID- 15729529
TI  - Aetiopathogenesis and long-term outcome of isolated pontine infarcts.
AB  - BACKGROUND AND PURPOSE: Isolated pontine strokes cause characteristic
      neurological syndromes and have a good short-term prognosis. The aim of this
      study was to examine the long-term survival, cumulative recurrence rate and
      clinical handicap of patients with isolated pontine infarcts of different
      aetiology. METHODS: One hundred consecutive patients with an isolated pontine
      infarction were identified by imaging studies and evaluated prospectively. After
      extensive study, cases were classified according to the aetiopathogenetic
      mechanisms: stroke due to basilar artery branch disease (BABD), small-artery
      disease (SAD) and large-artery-occlusive disease (LAOD). During a mean follow-up
      period of 46 months, stroke presentation and initial course, early and long-term
      mortality, disability and recurrence were evaluated. RESULTS: BABD was the most
      frequent cause of isolated pontine ischaemia (43%), followed by SAD (34%) and
      LAOD (21%). Hypertension was the most prominent risk factor, especially among
      patients with SAD (94.1%). Neurological impairment on admission was more severe
      in the LAOD group, followed by BABD. After 1 month patients with LAOD had the
      highest cumulative mortality (14.3%, p = 0.026) and more severe disability
      (61.1%, p = 0.001). Five-year mortality rate was 20.6%, 14% and 23.8% in the SAD
      , BABD- and in LAOD-group respectively (p = 0.776). Cumulative 5-year recurrence
      rate was 2.3 % for BABD, 14.3 % for LAOD, and 29.4 % for SAD (p = 0.011).
      CONCLUSIONS: Overall long-term survival of patients with isolated pontine
      infarcts is good. Initial differences regarding short-term outcome in infarctions
      of different aetiology resolve with time. Effective secondary prevention among
      SAD patients may limit stroke recurrence and positively influence long-term
      prognosis.

PMID- 15729530
TI  - Deep brain stimulation in late stage Parkinson's disease: a retrospective cost
      analysis in Germany.
AB  - During the last few years, deep brain stimulation (DBS) of the subthalamic
      nucleus (STN) has emerged as a promising therapy, alleviating major motor
      symptoms of Parkinson's disease (PD). However, in times of growing budgetary
      limitations, medical decisions are no longer merely based on clinical efficacy,
      but also on cost-effectiveness. Here we assess treatment costs (i. e. costs for
      conservative pharmacological treatment and all in-patient admissions) of 46 PD
      patients for one year before and two years after STN-DBS. The present data show
      that total treatment costs were increased by 32% for the first year and decreased
      by 54% for the second year of STN-DBS in comparison with preoperative values
      while the Unified Parkinson's Disease Rating Scale (UPDRS III) was significantly
      improved. The increase for the first year after surgery was mainly due to the
      implantation of the STN electrodes and the stimulation device. Taken together,
      STNDBS pays off from the second year of stimulation while motor symptoms are
      significantly improved. The present study provides first data of an important
      number of patients on clinical effectiveness and expenses in relation to STNDBS.

PMID- 15729531
TI  - Magnetic resonance imaging in patients with abduction deficit found after head
      trauma.

PMID- 15729533
TI  - Recurrent reversible posterior leukoencephalopathy in a patient with systemic
      lupus erythematosus.

PMID- 15729532
TI  - Ocular neuromyotonia with both tonic and paroxysmal components due to vascular
      compression.

PMID- 15729534
TI  - Diffuse cortical atrophy in a patient with Turner syndrome and Leber hereditary
      optic neuropathy.

PMID- 15729535
TI  - Ventriculitis and hydrocephalus as the primary manifestation of cerebral
      toxoplasmosis associated with AIDS.

PMID- 15729536
TI  - Posture-related cough headache and orthostatic drop in lumbar CSF pressure.

PMID- 15729538
TI  - Rene Descartes (1596-1650).

PMID- 15729537
TI  - Marked hypertrophy of the cauda equina in a patient with chronic inflammatory
      demyelinating polyradiculoneuropathy presenting as lumbar stenosis.

PMID- 15729542
TI  - Detection of diabetic retinopathy: a comparison between red-free digital images
      and colour transparencies.
AB  - BACKGROUND: The aim of this study was to compare how diabetic retinopathy was
      detected from red-free digital images and colour transparencies. METHODS: Two
      ophthalmologists graded two-field, nonstereoscopic, 60 degrees red-free digital
      images and colour transparencies utilizing an ETDRS-based grading scale, from 107
      mainly type 2 diabetic patients. The discordantly scored eyes were graded by the
      graders together to obtain a consensus level of retinopathy for each method. The
      eyes with discordant consensus grading results were further graded using all
      available photographic material to reach a final consensus level of diabetic
      retinopathy. Intermethod variations were presented as percentages and using kappa
      (k) and weighted kappa (wk) statistics. The errors of the two consensus gradings
      with respect to the final consensus grading were compared using McNemar's test.
      RESULTS: For the colour transparencies there was an agreement between the
      individual and the consensus grading results in 93% (k=0.90, wk=0.97) and 86%
      (k=0.79, wk 0.88) for grader 1 and grader 2. Corresponding figures for red-free
      digital images were 88% (k=0.83, wk=0.96) and 84% (k=0.78, wk 0.91). Agreement
      between methods was obtained in 76/107 eyes (71%; k=0.58 and wk=0.79). In the 31
      discordantly graded eyes the level of retinopathy was underestimated in 20/31
      (64%) vs 7/31 eyes (23%) and overestimated in 1/31 (3%) vs 3/31 eyes (10%) from
      colour transparencies and red-free digital images, respectively. The error
      tendencies were significantly lower when using red-free digital images (p<0.008).
      CONCLUSIONS: Red-free digital images are comparable with two-field colour
      transparencies in the identification of mild to moderate nonproliferative
      diabetic retinopathy.

PMID- 15729543
TI  - Spectroscopy challenge 9.

PMID- 15729544
TI  - New trends in biosensors for health care.

PMID- 15729545
TI  - On-line FT-Raman and dispersive Raman spectra database of artists' materials (e
      VISART database).
AB  - Raman spectroscopy has been widely applied in the analysis of different types of
      artwork. This technique is sensitive, reliable, non-destructive and can be used
      in situ. However, there are few references in the literature regarding specific
      Raman spectra libraries for the field of artwork analysis. In this paper, the
      development of two on-line databases with Fourier transform Raman (FT-Raman; 1064
      nm) and dispersive Raman (785 nm) spectra of materials used in fine art is
      presented; both are implemented in the e-vibrational spectroscopic databases of
      artists' materials database (e-VISART). The database provides not only spectra,
      but also information about each pigment. It must be highlighted that for each
      pigment or material several spectra are available from different dealers. Some of
      the FT-Raman spectra available in the e-VISART database have not been published
      until now. Some examples in which the e-VISART database has been successfully
      used are presented.

PMID- 15729546
TI  - Simultaneous determination of DTPA, EDTA, and NTA by capillary electrophoresis
      after complexation with copper.
AB  - We present a method for simultaneous determination of the aminopolycarboxylic
      acids DTPA, EDTA and NTA in dishwashing detergents, paper mill waters, and
      natural waters by capillary electrophoresis (CE). The complexing agents were
      examined as their copper(II) complexes and separated by conventional CE with
      reversed polarity of the applied voltage. The optimum separation conditions were
      established by varying the pH and phosphate and tetradecyltrimethylammonium
      bromide (TTAB) concentrations in the run buffer. The separations were carried out
      in a fused-silica capillary (61 cmx75 microm i.d.) filled with phosphate buffer
      (80 mmol L(-1), TTAB concentration 0.5 mmol L(-1), pH 7.1, voltage -20 kV) using
      direct UV detection at 191 and 254 nm. With this CE method all the peaks in the
      electropherograms were properly separated, the calibration plots gave good
      correlation coefficients and all three complexing agents could be detected in
      less than 4 min. Linear calibration plots were obtained for CuDTPA, CuEDTA and
      CuNTA; limits of detection were 0.03 mmol L(-1) for all complexing agents and
      recoveries for all tested samples were within the range 104+/-7%. Results
      obtained from dishwashing detergent samples were found to be reliable and
      comparable with those from HPLC (R2=0.989) and UV-Vis (R(2)=0.985) methods.

PMID- 15729547
TI  - Determination of lead in bone tissues by axially viewed inductively coupled
      plasma multichannel-based emission spectrometry.
AB  - A new procedure for determining low levels of lead in bone tissues has been
      developed. After wet acid digestion in a pressurized microwave-heated system, the
      solution was analyzed by inductively coupled plasma multichannel-based emission
      spectrometry. Internal standardization using the Co 228.615 nm reference line was
      chosen as the optimal method to compensate for the matrix effects from the
      presence of calcium and nitric acid at high concentration levels. The detection
      limit of the procedure was 0.11 microg Pb g(-1) dry mass. Instrumental precision
      at the analytical concentration of approximately 10 microg l(-1) ranged from 6.1
      to 9.4%. Precision of the sample preparation step was 5.4%. The concentration of
      lead in SRM 1486 (1.32+/-0.04 microg g(-1)) found using the new procedure was in
      excellent agreement with the certified level (1.335+/-0.014 microg g(-1)).
      Finally, the method was applied to determine the lead in various fish bone
      tissues, and the analytical results were found to be in good agreement with those
      obtained through differential pulse anodic stripping voltammetry. The method is
      therefore suitable for the reliable determination of lead at concentration levels
      of below 1 microg g(-1) in bone samples. Moreover, the multi-element capability
      of the technique allows us to simultaneously determine other major or trace
      elements in order to investigate inter-element correlation and to compute
      enrichment factors, making the proposed procedure particularly useful for
      investigating lead occurrence and pathways in fish bone tissues in order to find
      suitable biomarkers for the Antarctic marine environment.

PMID- 15729548
TI  - Use of near-infrared reflectance spectroscopy in predicting nitrogen, phosphorus
      and calcium contents in heterogeneous woody plant species.
AB  - Near-infrared reflectance spectroscopy was applied to determine nitrogen (N),
      phosphorus (P) and calcium (Ca) content in leaf samples of 18 woody species. A
      total of 183 samples from mountain, riparian and dry areas from the Central
      Western Iberian Peninsula were collected for this purpose. The wide intervals of
      variation observed in nutrient concentrations (6.6-45.0 g kg(-1) for N, 0.24-2.97
      g kg(-1) for P, and 1.00-20.06 g kg(-1) for Ca) were due to the great
      heterogeneity of the samples. To develop calibration equations, multiple linear
      regression, and partial least-squares regression (PLSR) were used. In both cases,
      three mathematical transformations of the data were applied: log1/R and first and
      second derivatives. The best calibration statistics were obtained using PLSR and
      derivative transformations (second derivative for N and first derivative for P
      and Ca). The following coefficients of multiple determination (R2) and standard
      errors of cross validation were obtained: 0.99 and 0.93 for N, 0.94 and 0.15 for
      P, and 0.95 and 0.88 for Ca. In the external validation the standard errors of
      prediction obtained were 0.76 (N), 0.11 (P) and 0.60 (Ca).

PMID- 15729549
TI  - A rare case of nasal glioma in the sphenoid sinus of an adult presenting with
      meningoencephalitis.
AB  - Nasal gliomas are rare embryologic development defects that commonly present
      shortly after birth. Very few cases have ever been reported in adults. Of those
      presenting in adult life, most were casual findings in patients with no symptoms.
      Rare localizations have been described in the nasopharynx, soft palate, orbital
      cave and scalp. We present an unusual case of a 56-year-old man who initially
      presented with meningoencephalitis and was found to have nasal glioma in the
      sphenoid sinus. Having discussed their embryology and histology, we conclude that
      MRI scanning is the preferred method of investigation. However, radiological
      evaluation preoperatively should not lead to any sense of security if no bony
      defect (and thus, the possibility of intracranial extension) is demonstrated.
      Extirpation via a functional surgical approach is the treatment of choice to
      prevent deformities in the facial bones. This can range from direct incision over
      the gliomata to removal transnasally by endoscopy or using a lateral rhinotomy
      approach depending on the location, size and involvement of the glioma.

PMID- 15729550
TI  - Sex- and menstrual cycle-related differences in sweating and cutaneous blood flow
      in response to passive heat exposure.
AB  - To examine sex- and menstrual cycle-related differences in thermoregulatory
      responses to heat exposure, ten young women and six young men were heated
      passively by immersing their legs in water heated to 42 degrees C for 60 min (in
      ambient conditions of 30 degrees C and 45% relative humidity). The women
      underwent heat exposure during the mid-follicular (F) and mid-luteal (L) phases
      of the menstrual cycle, which were confirmed by assaying plasma female
      reproductive hormones. The rectal and mean body (T(b)) temperatures of women in
      the L phase were significantly greater than those of women in the F phase and of
      men during a pre-heating equilibration period (28 degrees C) and during heat
      exposure. During heat exposure, the local sweat rates (m(sw)) on the forehead,
      chest, back, and forearm of women in either phase were significantly lower than
      those of men, but the thigh (m(sw)) was similar to that of men. The m(sw) did not
      change at any site during the different phases of the menstrual cycle. The
      cutaneous blood flow (%LDF) was significantly greater on the thigh for women in
      either phase compared with men, but no difference was found at any other site
      (forehead, chest, back, and forearm). The %LDF on the back was significantly
      greater for women in the L phase than in the F phase, but those at other sites
      were similar in both phases. We conclude that, compared with men, heat loss from
      women depends more on cutaneous vasodilation (especially on the thigh) than on
      sweating, irrespective of the phase of the menstrual cycle. This phenomenon was
      due to peripheral mechanisms, as reflected in the greater slope of the
      relationship between %LDF and T(b) lower slope of the relationship between m(sw))
      and frequency of sweat expulsion, and lower sweat output per gland. The menstrual
      cycle modified the T(b) threshold for vasodilation and sweat onset in women.
      Therefore, the sex difference in the T(b) threshold was more marked for women
      during the L phase than during the F phase. Moreover, the menstrual cycle
      modified the slope of the relationship between %LDF on the back and T(b).

PMID- 15729551
TI  - Strain and elongation of the vastus lateralis aponeurosis and tendon in vivo
      during maximal isometric contraction.
AB  - The strain and elongation of the vastus lateralis (VL) tendon, tendon plus
      aponeurosis, and aponeurosis were examined during maximal voluntary contractions
      on a Biodex-dynamometer (knee angle 115 degrees , hip angle 140 degrees ) in 12
      sprinters. Following a warm-up phase, the subjects were instructed to perform a
      gradual maximal knee extension and hold it for about 3 s. The kinematics of the
      leg were recorded using a Vicon 512 system with eight cameras operating at 120
      Hz. Ultrasonography images were taken simultaneously from the VL myotendinous
      junction and the mid lateral part of the VL muscle belly. During the maximal
      isometric knee extensions, the knee joint rotated (13.6+/-5.9 degrees ), leading
      to an overestimation of the elongation of the tendinous tissues. After correcting
      for this, the maximal elongation of the VL tendon examined at the myotendinous
      junction was lower (P<0.05) than the maximal elongation of the VL tendon plus
      aponeurosis examined at the muscle belly (15 vs. 27 mm, respectively). The
      maximal estimated strains of the tendon, tendon plus aponeurosis, and aponeurosis
      showed no statistical differences (8+/-2%, 8+/-1%, and 7+/-2%, respectively,
      P>0.05). It is concluded that the strains of the human VL tendon, VL tendon plus
      aponeurosis, and VL aponeurosis, as estimated in vivo by two dimensional
      ultrasound during maximal isometric contractions, do not differ from each other.
      The displacement measured at a cross point in the VL muscle belly is
      significantly greater than that measured at the VL myotendinous junction.

PMID- 15729552
TI  - Patient satisfaction and quality of life in cancer outpatients: results of the
      PASQOC study.
AB  - BACKGROUND: Satisfaction with care and quality of life (QoL) are indicative of
      the quality of care of cancer patients. The purpose of this study was to lay a
      cornerstone for patient-centred quality management by assessing the current
      status of satisfaction with care and QoL among oncological outpatients in
      Germany, and by identifying the key factors that determine a patient's
      willingness to recommend a medical facility. PATIENTS AND METHODS: A self
      constructed and validated patient satisfaction questionnaire plus the SF-36 were
      distributed to a random sample of 3384 cancer patients who presented at 24
      investigators' offices nationwide within a defined recruiting period and who met
      the inclusion criteria. The return rate was 81.9% (n=2772). A total of 2659
      (78.6%) questionnaires were evaluable. The most common cancer types were breast
      (22.9%) and intestine (19.8%). RESULTS: Overall satisfaction was high, but
      specific reporting questions revealed many areas for improvement such as shared
      decision making, doctor-patient communication and organization of care. QoL was
      significantly impaired in many domains. Patient-provider relationship, facility
      setting and information on diagnosis and treatment options are major determinants
      of a patient's willingness to recommend a facility to a friend or relative if
      needed. CONCLUSIONS: This multicentre study focusing on patient perspectives
      highlights that, although the overall degree of satisfaction was quite high,
      there are numerous areas for improvement.

PMID- 15729554
TI  - Utrophin is lacking at the neuromuscular junctions in the extraocular muscles of
      normal cat: artefact or true?
AB  - Extraocular muscles (EOM) are typically spared in Duchenne muscular dystrophy. We
      hypothesized that this might be due to different patterns of utrophin expression.
      The expression of utrophin was examined in EOM of normal cats using
      immunohistochemical methods and Western blot. For detecting acetylcholine
      receptors (AChR), we used alpha-bungarotoxin. Surprisingly, alpha-bungarotoxin
      failed to stain the AChR and no expression of utrophin could be detected at the
      neuromuscular junctions. Our study could indicate that the expression of utrophin
      is dependent on the structure of the AChR.

PMID- 15729555
TI  - Creation of Rhizopus oryzae lipase having a unique oxyanion hole by combinatorial
      mutagenesis in the lid domain.
AB  - Combinatorial libraries of the lid domain of Rhizopus oryzae lipase (ROL;
      Phe88Xaa, Ala91Xaa, Ile92Xaa) were displayed on the yeast cell surface using
      yeast cell-surface engineering. Among the 40,000 transformants in which ROL
      mutants were displayed on the yeast cell surface, ten clones showed clear halos
      on soybean oil-containing plates. Among these, some clones exhibited high
      activities toward fatty acid esters of fluorescein and contained non-polar amino
      acid residues in the mutated positions. Computer modeling of the mutants revealed
      that hydrophobic interactions between the substrates and amino acid residues in
      the open form of the lid might be critical for ROL activity. Based on these
      results, Thr93 and Asp94 were further combinatorially mutated. Among 6,000
      transformants, the Thr93Thr, Asp94Ser and Thr93Ser, Asp94Ser transformants
      exhibited a significant shift in substrate specificity toward a short-chain
      substrate. Computer modeling of these mutants suggested that a unique oxyanion
      hole, which is composed of Thr85 Ogamma and Ser94 Ogamma, was formed and thus the
      substrate specificity was changed. Therefore, coupling combinatorial mutagenesis
      with the cell surface display of ROL could lead to the production of a unique ROL
      mutant.

PMID- 15729556
TI  - Fed-batch bioreactor production of mannosylerythritol lipids secreted by
      Pseudozyma aphidis.
AB  - Two strains of Pseudozyma aphidis, DSM 70725 and DSM 14930, were used for the
      bioreactor production of mannosylerythritol lipids (MELs). Foam formation
      interfered substantially with the cultivation process. Soybean oil was
      simultaneously employed as both carbon source and anti-foam agent. Primary MEL
      formation occurred after nitrate limitation. After a first short time-period of
      nitrate limitation and further nitrate addition, MELs were secreted in spite of
      nitrate excess. The sedimentation of MEL-enriched beads indicated enhanced
      product formation. Maximum yield, productivity and yield coefficient of 165 g l(
      1), 13.9 g l(-1) day(-1) and 0.92 g g(-1) were achieved using strain DSM 14930
      with additional substrate-feeding (glucose, sodium nitrate, yeast extract) and a
      foam-controlled soybean oil supply.

PMID- 15729557
TI  - Degradation of anthracene and pyrene supplied by microcrystals and non-aqueous
      phase liquids.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are worldwide environmental pollutants.
      Their bioavailability is limited by a low aqueous solubility, which causes
      specific adaptations in degrading bacteria. To compare bacterial degrading
      behavior, a study was conducted on the mineralization, metabolization and
      formation of biomass from (14)C-anthracene by Sphingomonas sp. BA2 compared with
      those from (14)C-pyrene by Gordonia-like strain BP9 and Mycobacterium gilvum VF1.
      Different conditions of PAH supply were used in the medium: crystals <0.5 mm,
      microcrystals <<0.1 mm formed by sonication, or PAH solubilized in 2,2,4,4,6,8,8
      heptamethylnonane (HMN) or silicone oil. Anthracene supply by crystals and
      silicone oil led to similar maximum mineralization rates 33 ng ml(-1) h(-1) and
      the same amount of mineralization (24%) after 168 h. Microcrystals increased the
      rates and amounts only slightly. HMN decreased the values to less than one-third.
      In comparison with crystals, microcrystals increased overall pyrene
      mineralization by strain BP9 from 53% to 58%, with maximum mineralization rates
      of 160 ng ml(-1) h(-1) and 166 ng ml(-1) h(-1). Silicone oil heavily increased
      the rate to 292 ng ml(-1) h(-1) and the amount mineralized to 71%, whereas HMN
      inhibited the degradation by one order of magnitude. A similar degradation
      behavior showing lower mineralization rates and extent was observed with strain
      VF1. However, inhibition by HMN was less pronounced. Sonication, leading to
      decreased PAH crystal size, increased the mass transfer and mineralization rates.
      PAH supply by silicone oil led to a much higher mass transfer, which may be due
      to emulsification of the oil, whereas such effects were not observed with HMN.

PMID- 15729553
TI  - Enteric co-innervation of motor endplates in the esophagus: state of the art ten
      years after.
AB  - The existence of a distinct ganglionated myenteric plexus between the two layers
      of the striated tunica muscularis of the mammalian esophagus represented an
      enigma for quite a while. Although an enteric co-innervation of vagally
      innervated motor endplates in the esophagus has been repeatedly suggested, it was
      not possible until recently to demonstrate this dual innervation. Ten years ago,
      we were able to demonstrate that motor endplates in the rat esophagus receive a
      dual innervation from both vagal nerve fibers originating in the brain stem and
      from varicose enteric nerve fibers originating in the myenteric plexus. Since
      then, a considerable amount of data could be raised on enteric co-innervation and
      its occurrence in a variety of species, including humans, its neurochemistry,
      spatial relationships on motor endplates, ontogeny, and possible roles during
      esophageal peristalsis. These data underline the significance of this newly
      discovered innervation component, although its function is still largely unknown.
      The aim of this review is to summarize current knowledge about enteric co
      innervation of esophageal striated muscle and to provide some hints as to its
      functional significance.

PMID- 15729558
TI  - Impact of tumor size on the long-term survival of patients with early stage renal
      cell cancer.
AB  - As the biological behaviour of even early stage renal cell cancer (RCC) strongly
      correlates with tumor size, it has been argued that the inclusion of RCC up to a
      maximum diameter of 7 cm into a common subgroup classified as T1 according to the
      5th edition of the TNM system would not adequately represent the different
      biological aggressiveness of these malignancies. Taking this into account, the
      TNM classification, which now categorizes T1 RCC as T1a and T1b according to a
      cutoff size of 4 cm, was recently modified. However, only a few larger
      investigations, mainly based on univariate statistical analyses, that support the
      suitability of this cutoff are at present available from the literature.
      Therefore, it was the aim of the present investigation to determine the tumor
      size that best separates patients with low responses from those with high risk
      for tumor progression by univariate (log rank test) and multivariate (Cox
      regression model) statistical analyses. Between 1981 and 2000, 652 patients (443
      males and 209 females) underwent tumor nephrectomy in our clinic for the
      diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local
      growth not extending beyond the renal capsula at the time of surgery. For the
      different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm)
      that were selected to subdivide the patients into groups according to the maximum
      tumor diameter, the correlation between tumor size and overall survival was
      determined by univariate and multivariate statistical analyses. It became evident
      that although during univariate analysis the prognostic value of a cutoff size of
      4 cm was confirmed, multivariate analysis identified the highest relative risk
      for cause-specific death (2.93) for patients having tumors larger than 5 cm in
      maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical
      prognosis of patients undergoing tumor nephrectomy for early stage RCC. The
      present study demonstrates the need for multivariate statistical approaches when
      the latest modification of the TNM classification system is critically evaluated.

PMID- 15729559
TI  - Severe combined immunodeficiency caused by a splicing abnormality of the CD3delta
      gene.
AB  - CD3delta deficiency is a recently identified rare form of severe combined
      immunodeficiency. We analysed the CD3delta gene in a Japanese family with severe
      combined immunodeficiency. The patients lacked T-cells with normal numbers of B
      cells and natural killer cells in peripheral blood. We found a novel homozygous
      mutation in the splicing acceptor site of intron 2 (IVS2-2A --> G) in these
      patients. Analysis of patients' mononuclear cells revealed the CD3delta splicing
      abnormality. Chest X-ray films and computed tomography revealed small sized
      thymuses in these patients. CONCLUSION: The CD3delta gene should be analysed in
      patients with severe combined immunodeficiency lacking T-cells with normal B- and
      natural killer cells irrespective of the thymus size.

PMID- 15729560
TI  - Severe metformin intoxication with lactic acidosis in an adolescent.
AB  - A 15-year-old healthy girl ingested 38.25 g (0.55 g/kg body weight) of metformin
      in a suicide attempt. Subsequently she developed lactic acidosis and moderate
      renal failure. An initial session of haemodialysis was able to treat the acidosis
      and reduce the toxic level of metformin. Nevertheless, a further increase in
      serum lactate was observed during and after the first dialysis treatment. A
      second session of haemodialysis was started 5 h after the end of the first
      session and resulted in a lowering of the lactate level and an almost total
      elimination of metformin. During the further clinical course, reversible acute
      renal failure with a maximum creatinine of 2.4 mg/dl was observed. CONCLUSION:
      Despite sufficient haemodialysis, the production of lactate can be greater than
      the elimination in the case of severe metformin intoxication. Therefore
      haemodialysis should be continued even in the situation of rising lactate levels
      during the treatment.

PMID- 15729561
TI  - Is urorectal septum malformation sequence a variant of the vertebral defects,
      anal atresia, tracheo-oesophageal fistula, renal defects and radial dysplasia
      association? Report of a case and a review of the literature.
AB  - The urorectal septum malformation sequence (URSMS) consists of multiple systems
      anomalies including ambiguous genitalia, the absence of a perineal opening, an
      imperforate anus, and urogenital, colonic and lumbosacral anomalies. We describe
      a 3-day-old female infant with characteristic URSMS and review its clinical
      manifestations, outcomes and putative pathogenesis. We also compare its
      characteristics with those of the vertebral defects, anal atresia, tracheo
      oesophageal fistula, renal defects and radial dysplasia (VATER) association.
      CONCLUSION: Although defects of the urorectal septum malformation sequence and
      the vertebral defects, anal atresia, tracheo-oesophageal fistula, renal defects
      and radial dysplasia association overlap, we believe that they are separate
      entities. Differentiating the urorectal septum malformation sequence from
      vertebral defects, anal atresia, tracheo-oesophageal fistula, renal defects and
      radial dysplasia association is helpful to develop appropriate clinical
      investigations and search for the aetiology and pathogenesis of these diseases.

PMID- 15729562
TI  - MR imaging of the metacarpophalangeal joints of the fingers: evaluation of 38
      patients with chronic joint disability.
AB  - OBJECTIVE: To report the MR imaging findings of painful injured
      metacarpophalangeal (MCP) joints of the fingers. DESIGN AND PATIENTS: MR imaging
      of 39 injured MCP joints in 38 patients was performed after a mean delay of 8.8
      months. The MR images were obtained with the fingers in extended and flexed
      positions using T2-weighted and T1-weighted sequences before and after
      intravenous injection of a gadolinium compound. Ten patients were treated
      surgically. Mean clinical follow-up was 1.8 years. RESULTS: Tears of the
      collateral ligaments were the most common lesion (30/39), most being radial in
      location. Contrast-enhanced axial T1-weighted images with the MCP joint in a
      flexed position showed these lesions optimally. Ten tears were partial and 20
      were complete. In 13 patients, MR images showed 17 associated lesions including
      injuries of the extensor hood (10/17), interosseous tendon (3/17), palmar plate
      (3/17), and an osteochondral lesion (1/17). Sagittal MR images were essential to
      highlight palmar plate tears. CONCLUSION: Partial or complete tears of the
      collateral ligaments are prevalent MR imaging findings in patients with chronic
      disability resulting from injuries to the MCP joints. Although conservative
      treatment generally is sufficient for isolated injuries of the collateral
      ligaments, surgical repair is often required in cases of more extensive injuries.
      MR imaging may clearly delineate associated lesions of and about the MCP joints.

PMID- 15729563
TI  - Coronary artery calcification score by multislice computed tomography predicts
      the outcome of dobutamine cardiovascular magnetic resonance imaging.
AB  - The aim of this study was to determine whether a coronary artery calcium (CAC)
      score of less than 11 can reliably rule out myocardial ischemia detected by
      dobutamine cardiovascular magnetic resonance imaging (CMR) in patients suspected
      of having myocardial ischemia. In 114 of 136 consecutive patients clinically
      suspected of myocardial ischemia with an inconclusive diagnosis of myocardial
      ischemia, dobutamine CMR was performed and the CAC score was determined. The CAC
      score was obtained by 16-row multidetector compued tomography (MDCT) and was
      calculated according to the method of Agatston. The CAC score and the results of
      the dobutamine CMR were correlated and the positive predictive value (PPV) and
      the negative predictive value (NPV) of the CAC score for dobutamine CMR were
      calculated. A total of 114 (87%) of the patients were eligible for this study.
      There was a significant correlation between the CAC score and dobutamine CMR
      (p<0.001). Patients with a CAC score of less than 11 showed no signs of inducible
      ischemia during dobutamine CMR. For a CAC score of less than 101, the NPV and the
      PPV of the CAC score for the outcome of dobutamine CMR were, respectively, 0.96
      and 0.29. In patients with an inconclusive diagnosis of myocardial ischemia a
      MDCT CAC score of less than 11 reliably rules out myocardial ischemia detected by
      dobutamine CMR.

PMID- 15729564
TI  - Uterine restoration after repeated sloughing of fibroids or vaginal expulsion
      following uterine artery embolization.
AB  - The aim of our study is to present our experience with uterine restoration after
      repeated sloughing of uterine fibroids or transvaginal expulsion following
      uterine artery embolization (UAE) and to determine its safety and outcome. One
      hundred and twenty-four women (mean age, 40.3 years; age range, 29-52 years) with
      symptomatic uterine fibroids were included in this retrospective study. We
      performed arterial embolization with poly(vinyl alcohol) particles (250-710
      microm). Clinical symptoms and follow-up information for each patient were
      obtained through medical records. At an average of 3.5 months (range, 1-8 months)
      after embolization, magnetic resonance imaging examinations with T1- and T2
      weighted and gadolinium-enhanced T1-weighted images were obtained for all
      patients. The mean follow-up duration was 120 days (90-240 days). Eight (6.5%)
      patients experienced uterine restoration after repeated sloughing of uterine
      fibroids or spontaneous transvaginal expulsion. The locations of the leiomyomas
      were submucosal (n=5), intramural (n=2) and transmural (n=1). The maximum
      diameter of the fibroids ranged from 3.5 to 18.0 cm, with a mean of 8.4 cm. The
      time interval from embolization to the uterine restoration was 7-150 days (mean
      70.5 days). The clinical symptoms before and during vaginal sloughing or
      expulsion were lower abdominal pain (n=4), vaginal discharges (n=3), infection of
      necrotic myomas (n=2) and cramping abdominal pain (n=1). Gentle abdominal
      compression (n=1) and hysteroscopic assistance (n=1) were required to remove the
      whole fibroid. No other clinical sequelae, either early or delayed, were
      documented. Magnetic resonance images revealed the disappearance of leiomyomas,
      intracavitary rupture resulting in transformation of intramural or transmural
      myomas into submucosal myomas and localized uterine wall defects. Although the
      small size of this study precludes a strict conclusion, there appear to be few
      serious complications directly related to vaginal expulsion. Vaginal expulsion or
      fibroid sloughing is a possible course following UAE that is manageable, and the
      patients should be informed about this possibility.

PMID- 15729565
TI  - Monitoring of liver metastases after stereotactic radiotherapy using low-MI
      contrast-enhanced ultrasound--initial results.
AB  - The purpose of this study was to monitor liver metastases after radiotherapy
      using contrast-enhanced ultrasound (CEUS). In 15 patients, follow-up examinations
      after stereotactic, single-dose radiotherapy were performed using CEUS (low
      mechanical index (MI), 2.4-ml SonoVue) and computed tomography (CT). Besides
      tumor size, the enhancement of the liver and the metastases was assessed at the
      arterial, portal venous, and delayed phases. The sizes of the tumor and of a
      perifocal liver reaction after radiotherapy measured with CEUS significantly
      correlated with those measured at CT (r=0.93, p<0.001). CEUS found a significant
      reduction of the arterial vascularization in treated tumors (p<0.05). In the
      arterial phase, the perifocal liver tissue was hypervascularized compared to the
      treated tumor (p<0.001); in the late phase, it was less enhanced than the liver
      (p<0.001) and more than the tumor (p<0.01). The perifocal liver reaction was also
      seen in CT, but with a variable enhancement at the arterial (50% hyperdense
      compared to normal liver tissue), venous, or delayed phase (each with 70%
      hyperdense reactions). CEUS allows for the assessment of tumor and liver
      perfusion, in addition to morphological tumor examination, which was comparable
      with CT. Thus, changes of tumor perfusion, which may indicate tumor response, as
      well as the perifocal liver reaction after radiotherapy, which must be
      differentiated from perifocal tumor growth, can be sensitively visualized using
      CEUS.

PMID- 15729568
TI  - Induction of some defense-related genes and oxidative burst is required for the
      establishment of systemic acquired resistance in Capsicum annuum.
AB  - The inoculation of primary pepper leaves with an avirulent strain of Xanthomonas
      campestris pv. vesicatoria induced systemic acquired resistance (SAR) in the non
      inoculated, secondary leaves. This SAR response was accompanied by the systemic
      expression of the defense-related genes, a systemic microoxidative burst
      generating H2O2, and the systemic induction of both ion-leakage and callose
      deposition in the non-inoculated, secondary leaves. Some defense-related genes
      including those encoding PR-1, chitinase, osmotin, peroxidase, PR10, thionin, and
      SAR8.2 were markedly induced in the systemic leaves. The conspicuous systemic
      accumulation of H2O2 and the strong increase in peroxidase activity in the pepper
      leaves was suggested to play a role in the cell death process in the systemic
      micro-hypersensitive responses (HR), leading to the induction of the SAR.
      Treatment of the primary leaves with diphenylene iodinium (DPI), an inhibitor of
      oxidative burst, substantially reduced the induction of some of the defense
      related genes, and lowered the activation of the oxidative bursts in the systemic
      leaves distant from the site of the avirulent pathogen inoculation and
      subsequently SAR. Overall, these results suggest that the induction of some
      defense-related genes as well as a rapid increase in oxidative burst is essential
      for establishing SAR in pepper plants.

PMID- 15729569
TI  - Expectations about numerical events in four lemur species (Eulemur fulvus,
      Eulemur mongoz, Lemur catta and Varecia rubra).
AB  - Although much is known about how some primates--in particular, monkeys and apes-
      represent and enumerate different numbers of objects, very little is known about
      the numerical abilities of prosimian primates. Here, we explore how four lemur
      species (Eulemur fulvus, E. mongoz, Lemur catta, and Varecia rubra) represent
      small numbers of objects. Specifically, we presented lemurs with three expectancy
      violation looking time experiments aimed at exploring their expectations about a
      simple 1+1 addition event. In these experiments, we presented subjects with
      displays in which two lemons were sequentially added behind an occluder and then
      measured subjects' duration of looking to expected and unexpected outcomes. In
      experiment 1, subjects looked reliably longer at an unexpected outcome of only
      one object than at an expected outcome of two objects. Similarly, subjects in
      experiment 2 looked reliably longer at an unexpected outcome of three objects
      than at an expected outcome of two objects. In experiment 3, subjects looked
      reliably longer at an unexpected outcome of one object twice the size of the
      original than at an expected outcome of two objects of the original size. These
      results suggest that some prosimian primates understand the outcome of simple
      arithmetic operations. These results are discussed in light of similar findings
      in human infants and other adult primates.

PMID- 15729567
TI  - The role of natural killer cells in tumor control--effectors and regulators of
      adaptive immunity.
AB  - Natural killer (NK) cells are the primary effector cells of the innate immune
      system and have a well-established role in tumor rejection in a variety of
      spontaneous and induced cancer models. NK cell function is regulated by a complex
      balance of inhibitory and activating signals that allow them to selectively
      target and kill cells that display an abnormal pattern of cell surface molecules,
      while leaving normal healthy cells unharmed. In this review we discuss NK cell
      function, the role of NK cells in cancer therapies, the emerging concept of bi
      directional cross-talk between NK cells and dendritic cells, and the implications
      of these interactions for tumor immunotherapy.

PMID- 15729570
TI  - Islet autoantibodies in clinically diagnosed type 2 diabetes: prevalence and
      relationship with metabolic control (UKPDS 70).
AB  - AIMS/HYPOTHESIS: We examined the prevalence of islet autoantibodies and their
      relationship to glycaemic control over 10 years in patients diagnosed clinically
      with new-onset type 2 diabetes. METHODS: Patient clinical characteristics and
      autoantibody status were determined at entry to the UK Prospective Diabetes Study
      (UKPDS) before randomisation to different glucose control policies. Patients were
      followed for 10 years. RESULTS: Data available on 4,545 of the 5,102 UKPDS
      patients showed that 11.6% had antibodies to at least one of three antigens:
      islet cell cytoplasm, glutamic acid decarboxylase and islet autoantibody 2A (IA
      2A). Autoantibody-positive patients were younger, more often Caucasian and
      leaner, with lower beta cell function and higher insulin sensitivity than
      autoantibody-negative patients. They also had higher HbA1c, and HDL-cholesterol
      levels, and lower blood pressure, total cholesterol and plasma triglyceride
      levels. Despite relative hyperglycaemia, autoantibody-positive patients were less
      likely to have the metabolic syndrome (as defined by the National Cholesterol
      Education Program Adult Treatment Program III), reflecting a more beneficial
      overall risk factor profile. Of 3,867 patients with post-dietary run-in fasting
      plasma glucose (FPG) values between 6.0 and 14.9 mmol/l and no hyperglycaemic
      symptoms, 9.4% were autoantibody-positive, compared with 25.1% of 678 patients
      with FPG values of 15.0 mmol/l or higher, or hyperglycaemic symptoms. In both
      groups, no differences were seen between those with and without autoantibodies in
      changes to HbA1c over time, but autoantibody-positive patients required insulin
      treatment earlier, irrespective of the allocated therapy (p<0.0001).
      CONCLUSIONS/INTERPRETATION: Autoantibody-positive patients can be treated
      initially with sulphonylurea, but are likely to require insulin earlier than
      autoantibody-negative patients.

PMID- 15729572
TI  - The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: This study aimed to identify genes that are expressed in
      skeletal muscle, encode proteins with functional significance in mitochondria,
      and are associated with type 2 diabetes. METHODS: We screened for differentially
      expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and
      prioritised these on the basis of genomic localisation and bioinformatics
      analysis for proteins with likely mitochondrial functions. RESULTS: We identified
      a mitochondrial intramembrane protease, known as presenilins-associated rhomboid
      like protein (PSARL) that is associated with insulin resistance and type 2
      diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic
      Psammomys obesus, and restored after exercise training to successfully treat the
      diabetes. PSARL gene expression in human skeletal muscle was correlated with
      insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic
      euglycaemic clamp. In 1,031 human subjects, an amino acid substitution
      (Leu262Val) in PSARL was associated with increased plasma insulin concentration,
      a key risk factor for diabetes. Furthermore, this variant interacted strongly
      with age to affect insulin levels, accounting for 5% of the variation in plasma
      insulin in elderly subjects. CONCLUSIONS/INTERPRETATION: Variation in PSARL
      sequence and/or expression may be an important new risk factor for type 2
      diabetes and other components of the metabolic syndrome.

PMID- 15729571
TI  - A genetic and physiological study of impaired glucose homeostasis control in
      C57BL/6J mice.
AB  - AIMS/HYPOTHESIS: C57BL/6J mice exhibit impaired glucose tolerance. The aims of
      this study were to map the genetic loci underlying this phenotype, to further
      characterise the physiological defects and to identify candidate genes. METHODS:
      Glucose tolerance was measured in an intraperitoneal glucose tolerance test and
      genetic determinants mapped in an F2 intercross. Insulin sensitivity was measured
      by injecting insulin and following glucose disposal from the plasma. To measure
      beta cell function, insulin secretion and electrophysiological studies were
      carried out on isolated islets. Candidate genes were investigated by sequencing
      and quantitative RNA analysis. RESULTS: C57BL/6J mice showed normal insulin
      sensitivity and impaired insulin secretion. In beta cells, glucose did not
      stimulate a rise in intracellular calcium and its ability to close KATP channels
      was impaired. We identified three genetic loci responsible for the impaired
      glucose tolerance. Nicotinamide nucleotide transhydrogenase (Nnt) lies within one
      locus and is a nuclear-encoded mitochondrial proton pump. Expression of Nnt is
      more than sevenfold and fivefold lower respectively in C57BL/6J liver and islets.
      There is a missense mutation in exon 1 and a multi-exon deletion in the C57BL/6J
      gene. Glucokinase lies within the Gluchos2 locus and shows reduced enzyme
      activity in liver. CONCLUSIONS/INTERPRETATION: The C57BL/6J mouse strain exhibits
      plasma glucose intolerance reminiscent of human type 2 diabetes. Our data suggest
      a defect in beta cell glucose metabolism that results in reduced electrical
      activity and insulin secretion. We have identified three loci that are
      responsible for the inherited impaired plasma glucose tolerance and identified a
      novel candidate gene for contribution to glucose intolerance through reduced beta
      cell activity.

PMID- 15729573
TI  - Reduced insulin-stimulated GLUT4 bioavailability in stroke-prone spontaneously
      hypertensive rats.
AB  - AIMS/HYPOTHESIS: Insulin-stimulated glucose transport is impaired in a genetic
      model of hypertension, the stroke-prone spontaneously hypertensive rat (SHRSP),
      yet the molecular mechanisms that underlie this defect in the animals remain
      unclear. METHODS: We examined the effects of insulin on the trafficking of the
      insulin-responsive glucose transporter GLUT4 to the plasma membrane in isolated
      adipocytes from SHRSP and normotensive control Wistar-Kyoto (WKY) rats. RESULTS:
      Treatment of isolated adipocytes with insulin resulted in trafficking of GLUT4 to
      the plasma membrane. There was no significant difference in the magnitude of
      insulin-stimulated GLUT4 trafficking from intracellular membranes to the plasma
      membrane between strains. In contrast, we demonstrated that there is a
      significant reduction in GLUT4 accessible to the glucose photolabel Bio-LC-ATB
      BGPA at the plasma membrane of SHRSP adipocytes compared with control rats.
      CONCLUSIONS/INTERPRETATION: We propose that a large proportion of GLUT4
      translocated to the plasma membrane in response to insulin is not able to bind
      substrate and catalyse transport in the SHRSP. Therefore, there is a reduction in
      bioavailable GLUT4 in SHRSP animals that is likely to account, at least in part,
      for the reduced insulin-stimulated glucose uptake.

PMID- 15729574
TI  - Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell
      toxicity.
AB  - AIMS/HYPOTHESIS: Beta cell inflammation and cytokine-induced toxicity are central
      to autoimmune diabetes development. Lipid mediators generated upon lipoxygenase
      (LO) activation can participate in inflammatory pathways. 12LO-deficient mice are
      resistant to streptozotocin-induced diabetes. This study sought to characterise
      the cellular processes involving 12LO-activation lipid inflammatory mediator
      production in cytokine-treated pancreatic beta cells. METHODS: Islets and beta
      cell lines were treated with a combination of IL-1beta, IFN-gamma and TNF-alpha,
      or the 12LO product 12(S)-hydroxyeicosatetraenoic acid (HETE). Insulin secretion
      was measured using an enzyme immunoassay, and cell viability was evaluated using
      an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling
      assay. 12LO activity was evaluated and 12LO protein levels were determined using
      immunoblotting with a selective leucocyte type 12LO antibody. Cellular
      localisation of 12LO was evaluated using immunocytochemistry. RESULTS: Basal
      expression of leucocyte type 12LO protein was found in human and mouse islets and
      in several rodent beta cell lines. In mouse beta-TC3 cells, and in human islets,
      cytokines induced release of 12-HETE within 30 min. Cytokine addition also
      induced a rapid translocation of 12LO protein from the cytosol to the nucleus of
      beta-TC3 cells as shown by subcellular fractionation and immunostaining. Cytokine
      induced cell death and inhibition of insulin secretion were partially reversed by
      baicalein, a 12LO inhibitor. 12(S)-HETE inhibited beta-TC3 cell insulin release
      in a time- and concentration-dependent manner. Incubating beta-TC3 cells with 100
      nmol/l of 12(S)-HETE resulted in a 57% reduction in basal insulin release (6 h),
      and a 17% increase in cell death (18 h) as compared with untreated cells. 12(S)
      HETE activated the stress-activated protein kinase c-Jun N-terminal kinase and
      p38 within 15 min, as judged by increased kinase protein phosphorylation.
      CONCLUSIONS/INTERPRETATION: The data suggest that inflammatory cytokines rapidly
      activate 12LO and show for the first time that cytokines induce 12LO
      translocation. The effects of 12-HETE on insulin secretion, cytotoxicity and
      kinase activation were similar to the effects seen with cytokines. The results
      provide mechanistic information of cytokine-induced toxic effects on pancreatic
      beta cells and support the hypothesis that blocking 12LO activation could provide
      a new therapeutic way to protect pancreatic beta cells from autoimmune injury.

PMID- 15729575
TI  - Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells
      by a PPARgamma-independent mechanism.
AB  - AIMS/HYPOTHESIS: This study evaluated the hypothesis that peroxisome proliferator
      activated receptor-gamma (PPARgamma) agonists, including thiazolidinediones
      (TZDs) and the rexinoid LG100268 (LG), directly affect human vascular cell
      function (proliferation, cell cycle, protein expression, lactate release)
      independently of (1) their PPARgamma-activating potential and (2) the cells'
      vascular origin. METHODS: Human umbilical vein endothelial cells (HUVECs), human
      adult vein endothelial cells (HAVECs), human retinal endothelial cells (HRECs)
      and human retinal pericytes (HRPYCs) were incubated (48 h) with 2-50 micromol/l
      rosiglitazone (RSG), RWJ241947 (RWJ), pioglitazone (PIO), troglitazone (TRO), 15
      deoxy-Delta(12,14)-prostaglandin J2 (PGJ2) and LG. Proliferation, cell cycle
      distribution, protein expression, peroxisome proliferator-activated receptor
      responsive element (PPRE) transcriptional activity and mitochondrial effects were
      determined by [3H]thymidine incorporation, FACS analyses, western blots, reporter
      assays and lactate release respectively. RESULTS: In HUVECs, RSG, RWJ, PIO, TRO,
      PGJ2 and LG reduced (p<0.01) proliferation (due to a G0/G1 cell cycle arrest) by
      up to 23%, 36%, 38%, 86%, 99% and 93% respectively. The antiproliferative
      response was similar in HRPYCs and HAVECs, but was attenuated in HRECs. Whereas
      p21WAF-1/Cip1 and p27Kip were differently affected in HUVECs, all agents reduced
      (p<0.05) expression of cyclins (D3, A, E, B), cyclin-dependent kinase-2 and
      hyperphosphorylated retinoblastoma protein. The rank order of the
      antiproliferative effects of TZDs in HUVECs (RSG approximately PIO approximately
      RWJ<TRO) contrasted their PPRE transcriptional activities (TRO<PIO<RSG<RWJ), but
      correlated with cellular lactate release. Proliferation inhibition and lactate
      release were mimicked by rotenone (mitochondrial complex I inhibitor).
      CONCLUSIONS/INTERPRETATION: In conclusion, this study suggests that the
      antiproliferative action of the TZDs in vascular cells is independent of their
      PPARgamma-activating and associated insulin-sensitising potential, but could
      relate to mitochondrial mechanisms.

PMID- 15729576
TI  - Comparison of the effects on glucose and lipid metabolism of equipotent doses of
      insulin detemir and NPH insulin with a 16-h euglycaemic clamp.
AB  - AIMS/HYPOTHESIS: The association of insulin detemir with non-esterified fatty
      acid binding sites on albumin may limit its transfer from the circulation into
      the extravascular extracellular space in adipose tissue and muscle, due to the
      capillary endothelial cell barrier. In the liver, the open sinusoids may expose
      hepatocytes to insulin detemir, enabling it to have a greater effect in the liver
      than in peripheral tissues. METHODS: We investigated the effects of equipotent
      doses of insulin detemir and NPH insulin on hepatic glucose rate of appearance
      (Ra), peripheral glucose rate of disposal (Rd) and glycerol Ra (a measure of
      lipolysis) using stable isotope techniques. We also investigated the effects of
      these insulins on NEFA concentrations in seven healthy volunteers during a 16-h
      euglycaemic clamp. A higher dose of insulin detemir was also studied. RESULTS:
      There was no difference in the glucose infusion profile between insulin detemir
      and NPH. Insulin detemir had a greater effect on mean suppression of glucose Ra
      (mean difference 0.24 mg kg(-1) min(-1); CI 0.09-0.39; p<0.01), and minimum
      glucose Ra, with minimum low dose detemir -0.10+/-0.15 mg.kg(-1).min(-1) and
      minimum NPH 0.17+/-0.10 mg.kg(-1).min(-1) (p<0.02). However, it had a lesser
      effect on mean suppression of NEFA concentrations (mean difference -0.10 mmol/l;
      CI -0.03 to -0.17; ANOVA, p<0.02) than NPH. The effect of insulin detemir on
      glucose Rd and glycerol Ra was not different from NPH. Following high-dose
      detemir, total glucose infused and maximum glucose Rd were higher (p<0.02,
      p<0.03) and plasma NEFA concentrations lower (p<0.01) than with low-dose
      determir. CONCLUSIONS/INTERPRETATION: This study suggests that insulin detemir,
      when compared to NPH insulin, has a greater effect on the liver than on
      peripheral tissues and thus has the potential to restore the physiological
      insulin gradient.

PMID- 15729577
TI  - Low birthweight is associated with specific changes in muscle insulin-signalling
      protein expression.
AB  - AIMS/HYPOTHESIS: People with low birthweight have an increased risk of developing
      type 2 diabetes mellitus in adulthood. The mechanistic basis of this phenomenon
      is not known. Here we investigate the effect of early growth restriction on the
      expression of insulin-signalling proteins in skeletal muscle in a human cohort
      and a rat model. METHODS: We recruited 20 young men with low birthweight (mean
      birthweight 2702+/-202 g) and 20 age-matched control subjects (mean birthweight
      3801+/-99 g). Biopsies were obtained from the vastus lateralis muscle and protein
      expression of selected insulin-signalling proteins was determined. Rats used for
      this study were male offspring born to dams fed a standard (20%) protein diet or
      a low (8%) protein diet during pregnancy and lactation. Protein expression was
      determined in soleus muscle from adult offspring. RESULTS: Low-birthweight
      subjects showed reduced muscle expression of protein kinase C (PKC)zeta,
      p85alpha, p110beta and GLUT4. PKCzeta, GLUT4 and p85 were also reduced in the
      muscle of rats fed a low-protein diet. Other proteins studied were unchanged in
      low-birthweight humans and in rats fed a low-protein diet when compared with
      control groups. CONCLUSIONS/INTERPRETATION: We found decreased expression of
      specific insulin-signalling proteins in low-birthweight subjects compared to
      controls. These changes precede the onset of impaired glucose tolerance. The
      similarity of protein expression profile in the men with low birthweight compared
      to that of the offspring of rats fed a low-protein diet suggests that the rodent
      model is an accurate representation of the human situation. It also provides a
      potential mechanistic explanation as to why the fetal environment plays an
      important role in determining risk of developing type 2 diabetes.

PMID- 15729578
TI  - Ethnicity and sex are strong determinants of diabetes in an urban Western
      society: implications for prevention.
AB  - AIMS/HYPOTHESIS: This study was conducted to investigate the prevalence of
      diabetes and its association with ethnicity and sex, to identify subgroups at
      special risk. METHODS: We performed a population-based cross-sectional survey of
      30- to 67-year-olds in an area of Oslo with low socio-economic status, and
      collected data using questionnaires, physical examinations and serum analyses for
      the 2,513 participants (attendance rate 49.3%). RESULTS: In the age group 30-59
      years, mean BMI was 28.5 (95% CI: 27.5-29.6) for South Asian women, 26.1 (25.9
      26.4) for Western women, 26.7 (26.1-27.4) for South Asian men and 27.2 (26.9
      27.5) for Western men. The diabetes prevalence rates were 27.5% (18.1-36.9) for
      South Asian women, 2.9% (1.9-3.4) for Western women, 14.3% (8.0-20.7) for South
      Asian men and 5.9% (4.2-7.5) for Western men. The age-adjusted odds ratio (OR)
      for diabetes for women vs men was 1.9 (0.9-4.1) for South Asians, and 0.4 (0.3
      0.6) for the Western population (p<0.001). The age-adjusted OR for diabetes for
      South Asians vs Westerners was 11.0 (5.8-21.1) for women and 3.0 (1.6-5.4) for
      men, and after adjustment for WHR the ORs were 7.7 (3.9-15.3) for women and 2.6
      (1.4-4.9) for men. After additional adjustments for physical activity, education,
      body height and fertility for women, the OR was 6.0 (2.3-15.4) for women and 1.9
      (0.9-4.0) for men. CONCLUSIONS/INTERPRETATION: The alarmingly high prevalence of
      diabetes among South Asian women in Norway needs further investigation, as it has
      considerable public health implications. Ethnic differences in OR for diabetes
      persisted after adjustment for age, adiposity, physical activity and education.
      These differences were still present for women after additional adjustment for
      body height and fertility.

PMID- 15729580
TI  - Glucose-induced changes of multiple mouse islet proteins analysed by two
      dimensional gel electrophoresis and mass spectrometry.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate molecular mechanisms of
      glucose-induced changes in islets of Langerhans by analysing global changes in
      protein patterns of islets exposed to elevated glucose concentrations. METHODS:
      Islets were isolated from C57BL/6J mice and used either directly or after
      exposure to 11 mmol/l glucose for 24 h. Islet protein profiles were obtained by
      two-dimensional gel electrophoresis, and protein spots were identified by peptide
      mass fingerprinting using mass spectrometry. RESULTS: Two-dimensional gels of
      freshly isolated islets and islets exposed to 11 mmol/l glucose contained 1,074
      and 1,254 spots, respectively. The number of differentially expressed spots was
      379, with 20 spots appearing as new proteins in islets exposed to 11 mmol/l
      glucose. We identified 124 spots corresponding to 77 protein entries and
      generated a reference map from freshly isolated islets. Actin, alpha enolase,
      cytokeratin 8, endoplasmin, glucose-regulated proteins, heat shock proteins,
      peroxiredoxins, prohormone convertase 2, protein disulphide isomerase, superoxide
      dismutase, tubulin, and V-type H+ -ATPase (V1 subunit A) were upregulated in
      islets exposed to 11 mmol/l glucose. In contrast, exocrine proteins and
      secretagogin were downregulated in these islets compared with in freshly isolated
      islets. CONCLUSIONS/INTERPRETATION: The islet proteome approach revealed
      simultaneous changes in protein patterns of islets exposed to elevated glucose
      concentrations, indicating enhanced insulin synthesis, granular mobilisation and
      maturation, and increased stress response. The changes may be of relevance for
      the understanding of altered islet function in the hyperglycaemic state. It is
      expected that the islet reference map will become an important tool for
      dissecting multifactorial islet processes.

PMID- 15729579
TI  - Sural nerve pathology in diabetic patients with minimal but progressive
      neuropathy.
AB  - AIMS/HYPOTHESIS: The early pathological features of human diabetic neuropathy are
      not clearly defined. Therefore we quantified nerve fibre and microvascular
      pathology in sural nerve biopsies from diabetic patients with minimal neuropathy.
      METHODS: Twelve diabetic patients underwent detailed assessment of neuropathy and
      fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy
      8.7+/-0.6 years later. RESULTS: At baseline, neuropathic symptoms, neurological
      deficits, quantitative sensory testing, cardiac autonomic function and peripheral
      nerve electrophysiology showed minimal abnormality, which deteriorated at follow
      up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but
      teased fibre studies showed paranodal abnormalities (p<0.001), segmental
      demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration.
      Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density
      (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial
      capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell
      hyperplasia (p<0.004) and a reduction in luminal area (p<0.007).
      CONCLUSIONS/INTERPRETATION: The early pathological features of human diabetic
      neuropathy include an abnormality of the myelinated fibre Schwann cell and
      unmyelinated fibre degeneration with regeneration. These changes are accompanied
      by a significant endoneurial microangiopathy.

PMID- 15729581
TI  - The common T60N polymorphism of the lymphotoxin-alpha gene is associated with
      type 2 diabetes and other phenotypes of the metabolic syndrome.
AB  - AIMS/HYPOTHESIS: Associations between variations in the lymphotoxin-alpha gene
      (LTA) and myocardial infarction, cerebral infarction and type 1 diabetes have
      previously been reported. We hypothesised that, in its homozygous form, the
      functional T60N variant of LTA is associated with type 2 diabetes and other
      features of the metabolic syndrome among Danish Caucasian individuals. METHODS:
      The T60N polymorphism of LTA was genotyped in the population-based Inter99 study
      cohort (6,514 Caucasian subjects) and in a group of type 2 diabetic patients by
      analysis of PCR-generated primer extension products using high-throughput chip
      based matrix-assisted laser desorption/ionisation time-of-flight mass
      spectronomy. RESULTS: Comparison of 1,401 diabetic patients with 1,470 matched
      glucose-tolerant control subjects from the Inter99 cohort revealed that the
      frequency of the mutant at codon 60 in its homozygous form (N/N genotype) was
      higher among the diabetic patients than among the control subjects (14.6% [95% CI
      12.8-16.5] vs 12.0% [95% CI 10.3-13.7], p=0.048; odds ratio=1.24). This
      association was even stronger among the 131 patients with early-onset (diagnosis
      at 40 years or younger) diabetes (21.4% [95% CI 14.4-28.4] vs 12.0% [95% CI 10.3
      13.7], p=0.004; odds ratio=1.99). Additionally, studies of the metabolic syndrome
      (as defined by the 1999 World Health Organization criteria) in the Inter99 study
      cohort revealed that the frequency of the N/N LTA genotype was higher among
      subjects presenting one or more features of the metabolic syndrome (n=4,425) than
      among subjects with no characteristics of this syndrome (n=1,752) (p=0.026).
      CONCLUSIONS/INTERPRETATION: The T60N LTA polymorphism is associated with type 2
      diabetes and other features of the metabolic syndrome among Caucasian
      individuals.

PMID- 15729582
TI  - Defective antioxidative activity of small dense HDL3 particles in type 2
      diabetes: relationship to elevated oxidative stress and hyperglycaemia.
AB  - AIMS/HYPOTHESIS: Elevated oxidative stress, hyperglycaemia, and dyslipidaemia
      involving low levels of HDL particles are key proatherogenic factors in type 2
      diabetes mellitus. We examined the relationship of oxidative stress, and the
      degree of glycaemia and triglyceridaemia, to antioxidative function of HDL
      particle subspecies in type 2 diabetes. SUBJECTS AND METHODS: Five HDL
      subfractions (2b, 2a, 3a, 3b, 3c) were isolated by density gradient
      ultracentrifugation from well-controlled type 2 diabetic subjects (n=20) and
      normolipidaemic, non-diabetic controls (n=10). Specific antioxidative activity
      (capacity to protect LDL from oxidation on a unit particle mass or on a particle
      number basis), chemical composition and enzymatic activities were measured in
      each subfraction. Systemic oxidative stress was assessed as plasma levels of 8
      isoprostanes. RESULTS: Specific antioxidative activity of small dense HDL3b and
      3c particles in diabetic patients was significantly diminished (up to -47%, on a
      particle mass or particle number basis) as compared with controls. Plasma 8
      isoprostanes were markedly elevated (2.9-fold) in diabetic patients, were
      negatively correlated with both specific antioxidative activity of HDL3
      subfractions and plasma HDL cholesterol (HDL-C) levels, and were positively
      correlated with glycaemia and triglyceridaemia. Paraoxonase 1 activity was
      consistently lower in diabetic HDL subfractions and was positively correlated
      with HDL3 antioxidative activity. The altered chemical composition of diabetic
      HDL3 subfractions (core cholesteryl ester depletion, triglyceride enrichment) was
      equally correlated with diminished antioxidative activity.
      CONCLUSIONS/INTERPRETATION: Antioxidative activity of small dense HDL is
      deficient in type 2 diabetes, is intimately linked to oxidative stress, glycaemia
      and hypertriglyceridaemia and primarily reflects abnormal intrinsic
      physicochemical properties of HDL particles.

PMID- 15729583
TI  - Serum amyloid A: production by human white adipocyte and regulation by obesity
      and nutrition.
AB  - AIMS/HYPOTHESIS: The acute-phase proteins, serum amyloid As (SAA), are precursors
      of amyloid A, involved in the pathogenesis of AA amyloidosis. This work started
      with the characterisation of systemic AA amyloidosis concurrent with SAA
      overexpression in the subcutaneous white adipose tissue (sWAT) of an obese
      patient with a leptin receptor deficiency. In the present study a series of
      histopathological, cellular and gene expression studies was performed to assess
      the importance of SAA in common obesity and its possible production by mature
      adipocytes. MATERIALS AND METHODS: Gene expression profiling was performed in the
      sWAT of two extremely obese patients with a leptin receptor deficiency. Levels of
      the mRNAs of the different SAA isoforms were quantified in sWAT cellular
      fractions from lean subjects and from obese subjects before and after a very-low
      calorie diet. These values were subsequently compared with serum levels of SAA in
      these individuals. In addition, histopathological analyses of sWAT were performed
      in lean and obese subjects. RESULTS: In sWAT, the expression of SAA is more than
      20-fold higher in mature adipocytes than in the cells of the stroma vascular
      fraction (p<0.01). Levels of SAA mRNA expression and circulating levels of the
      protein are sixfold (p<0.001) and 3.5-fold (p<0.01) higher in obese subjects than
      in lean subjects, respectively. In lean subjects, 5% of adipocytes are
      immunoreactive for SAA, whereas the corresponding value is greater than 20% in
      obese subjects. Caloric restriction results in decreases of 45-75% in levels of
      the transcripts for the SAA isoforms and in circulating levels of the protein.
      CONCLUSIONS/INTERPRETATION: The results of the present study indicate that SAA is
      expressed by sWAT, and its production at this site is regulated by nutritional
      status. If amyloidosis is seen in the context of obesity, it is possible that
      production of SAA by adipocytes could be a contributory factor.

PMID- 15729584
TI  - 5-(Phenylthio)acyclouridine: a powerful enhancer of oral uridine bioavailability:
      relevance to chemotherapy with 5-fluorouracil and other uridine rescue regimens.
AB  - PURPOSE: The purpose of this investigation was to evaluate the effectiveness of
      oral 5-(phenylthio)acyclouridine (PTAU) in improving the pharmacokinetics and
      bioavailability of oral uridine. PTAU is a potent and specific inhibitor of
      uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine
      catabolism. This compound was designed as a lipophilic inhibitor in order to
      facilitate its access to the liver and intestine, the main organs involved in
      uridine catabolism. PTAU is fully absorbed after oral administration with 100%
      oral bioavailability. METHODS: Uridine (330, 660 or 1320 mg/kg) and/or PTAU (30,
      45, 60, 120, 240 or 480 mg/kg) were orally administered to mice. The plasma
      levels of uridine, its catabolite uracil, and PTAU were measured using HPLC, and
      pharmacokinetic analysis was performed. RESULTS: Oral PTAU up to 480 mg/kg per
      day is not toxic to mice. Oral PTAU at 30, 45, 60, 120 and 240 mg/kg has a
      prolonged plasma half-life of 2-3 h, and peak plasma PTAU concentrations (C(max))
      of 41, 51, 74, 126 and 161 microM with AUCs of 70, 99, 122, 173 and 225 micromol
      h/l, respectively. Coadministration of uridine with PTAU did not have a
      significant effect on the pharmacokinetic parameters of plasma PTAU at any of the
      doses tested. Coadministration of PTAU (30, 45, 60 and 120 or 240 mg/kg) with
      uridine (330, 660 or 1320 mg/kg) elevated the concentration of plasma uridine
      over that following the same dose of uridine alone, a result of reduced metabolic
      clearance of uridine as evidenced by decreased plasma exposure (C(max) and AUC)
      to uracil. Plasma uridine was elevated with the increase of uridine dose at each
      PTAU dose tested and no plateau was reached. Coadministration of PTAU at 30, 45,
      60, 120 and 240 mg/kg improved the low oral bioavailability (7.7%) of uridine
      administered at 1320 mg/kg by 4.3-, 5.9-, 9.9-, 11.7- and 12.5-fold,
      respectively, and reduced the AUC of plasma uracil (1227.8 micromol h/l) by 5.7-,
      6.8-, 8.2-, 6.3-, and 6.9-fold, respectively. Similar results were observed when
      PTAU was coadministered with lower doses of uridine. Oral PTAU at 30, 45, 60, 120
      and 240 mg/kg improved the oral bioavailability of 330 mg/kg uridine by 1.7-, 2.4
      , 2.6-, 5.2- and 4.3- fold, and that of 660 mg/kg uridine by 2.3-, 2.7-, 3.3-,
      4.6- and 6.7-fold, respectively. CONCLUSION: The excellent pharmacokinetic
      properties of PTAU, and its extraordinary effectiveness in improving the oral
      bioavailability of uridine, could be useful to rescue or protect from host
      toxicities of 5-fluorouracil and various chemotherapeutic pyrimidine analogues
      used in the treatment of cancer and AIDS, as well as in the management of medical
      disorders that are remedied by the administration of uridine including CNS
      disorders (e.g. Huntington's disease, bipolar disorder), liver diseases, diabetic
      neuropathy, cardiac damage, various autoimmune diseases, and transplant
      rejection.

PMID- 15729585
TI  - Mitochondrial electroporation and in organello RNA editing of chimeric atp6
      transcripts.
AB  - The Sorghum bicolor atp6-1 gene and chimeric atp6 genes with additional maize
      sequences were introduced into isolated maize mitochondria via electroporation.
      Transcripts isolated after in vitro incubation of the transformed organelles were
      then analysed for RNA editing. Transcripts of the S. bicolor atp6-1 gene, and the
      RNAs obtained from most of chimeric sorghum-maize atp6 gene constructs tested,
      were not edited. However, the transcript of one engineered chimeric gene
      comprising the 5'untranslated sequence and a segment of the N-terminal ORF of the
      maize atp6 combined with the sorghum atp6 core ORF and 3'untranslated sequence
      was found to be partially edited. We were able to exclude low RNA stability or
      insufficient editing capacity as the reason for failure to edit in the other
      instances. Instead, the data indicate that the maize sequence in the edited
      fusion transcript provides a structural motif or binding site for a transcript
      specific editing factor.

PMID- 15729586
TI  - Assessment of skeletal age at the wrist in children with a new ultrasound device.
AB  - BACKGROUND: Determination of skeletal development in children is important. The
      most common method of evaluation uses the standards of Greulich and Pyle (G and
      P) to assess the left hand radiograph. Numerous assessments may be made during
      follow-up. OBJECTIVE: The aim of our study was to compare the accuracy of a new
      sonographic method with the standard radiographic method. MATERIALS AND METHODS:
      Seventy consecutive patients (age 6-17 years; 34 girls, 36 boys) underwent
      radiography of the left hand, followed by sonographic examination of the same
      hand using the BonAge system (Sunlight Medical Ltd., Israel). This system
      evaluates the relationship between the velocity of sound passing thorough the
      distal radial and ulna epiphysis and growth, using gender- and ethnicity-based
      algorithms. One experienced paediatric radiologist analysed the radiograph and
      assigned bone age scores based on the G and P atlas for the whole left hand and
      for the distal radius alone. The radiologist was blinded to the chronological age
      (CA), height of the patient and the BonAge result. Correlation between BonAge and
      G and P was undertaken. RESULTS: In 65 patients, BonAge measurement could be
      performed successfully. In five patients, the scanning process was impossible
      using the ultrasound device. The r(2) (r is the Pearson correlation coefficient)
      of the BonAge ultrasound measurement and the G and P method was 0.82. The
      averaged accuracy (i.e. absolute difference in years between G and P reading and
      BonAge ultrasonic results) was calculated. Results were similar for boys and
      girls: 1.0+/-0.8 years for the whole left hand and 0.8+/-0.7 year for the distal
      radius. On average, the difference between BonAge and CA is the same as the
      difference between G and P and CA, i.e. 1.4 years. CONCLUSIONS: The BonAge device
      demonstrates the ability of ultrasound to produce an accurate assessment of bone
      age. The results are highly correlated with skeletal age evaluated conventionally
      using the G and P method. Obvious advantages of the ultrasound device are
      objectivity, lack of ionizing radiation, and easy accessibility.

PMID- 15729588
TI  - [Purtscher's syndrome. An example of a rare occurrence of ocular complication
      after thoracic compression trauma].
AB  - Purtscher's retinopathy is a traumatic angiopathy, most commonly caused by head
      and chest trauma. Retinal signs include white ischemic infarcts (cotton-wool
      spots or Purtscher flecken) and hemorrhages (dot and blot, preretinal, or flame).
      The prognosis for patients with decreased vision is unpredictable. We report one
      case of this disease developing 3 days after a motorcycle accident.

PMID- 15729587
TI  - [Value of early somatosensory evoked potentials in intubated and mechanically
      ventilated patients with craniocerebral trauma].
AB  - The objective of this study was to evaluate the prognostic value of early
      somatosensory evoked potentials (SEP) in patients with brain injury. A total of
      85 patients who had been intubated and mechanically ventilated were investigated
      retrospectively. The results were compared to the Glasgow Coma Scale (GCS). The
      Glasgow Coma Scale as determined by the emergency doctor at the accident site, an
      SEP score, and the outcome of the patient were compared. There was no correlation
      of the Glasgow Coma Scale with the outcome. Probably the reason for this finding
      is the short interval of time between accident and evaluation of the GCS so that
      an awakening of the patient a short time after the accident is not reflected by
      the GCS. On the other hand, there was a significant correlation of the SEP score
      in the first examination after the accident with the outcome (p<0.001). SEP gave
      no false pessimistic prognoses. All patients without cortical responses either in
      one hemisphere or both hemispheres remained in coma vigile or died because of
      their brain injury. If cortical responses over both hemispheres remained normal,
      it was highly probable that the patients were later not severely handicapped. A
      reliable prognosis based on SEP is possible at a time when the clinical
      examination of the patient is limited due to sedating drugs. Repetitive
      examinations can monitor the course of recovery and correct false optimistic
      prognoses. The method may be applied at bedside and requires minimal time and
      little financial effort.

PMID- 15729589
TI  - Entamoeba histolytica: focal adhesion kinase and Erk phosphorylation are altered
      in the cytoskeleton mutant BG-3.
AB  - The Entamoeba histolytica mutant BG-3 has several altered cytoskeletal
      properties, including the distribution of actin and certain surface
      characteristics such as osmolarity and electrophoretic mobility. By Western blot
      analysis and assays for cell adhesion to collagen, we demonstrate that mutant BG
      3 shows an increase in the phosphorylation levels of protein kinases that
      participate in proliferation, adhesion and migration, such as focal adhesion
      kinase and MAP kinase (Erk2), and that it has also altered its capacity of
      binding to collagen type I. These results indicate that E. histolytica
      cytoskeleton integrity plays an important role in adhesion and thus invasion of
      the host.

PMID- 15729590
TI  - Identification of proteins interacting with Toxoplasma SRCAP by yeast two-hybrid
      screening.
AB  - Toxoplasma gondii is an opportunistic protozoan parasite that differentiates into
      latent cysts (bradyzoite) that can be reactivated during immunosuppression.
      TgSRCAP (Toxoplasma gondii Snf2-related CBP activator protein) is a SWI2/SNF2
      family chromatin remodeler whose expression increases during cyst development.
      Identifying the proteins associating with TgSRCAP during the pre-cyst stage
      (tachyzoite) will increase our understanding of how parasite differentiation is
      initiated. We employed the yeast two-hybrid system to identify proteins that may
      interact directly with TgSRCAP. A stretch of 1,060 amino acids between ATPase
      subdomains IV and V of TgSRCAP was chosen as "bait" since the corresponding
      region in human SRCAP interacts with other proteins, including CREB binding
      protein. We have identified several novel parasite-specific transcription factors
      predicted to be in the T. gondii genome. Metabolic enzymes that may participate
      in cyst development were also identified as interacting with TgSRCAP.

PMID- 15729592
TI  - Significance of hypoxia in cervical cancer.

PMID- 15729593
TI  - Cancer pharmacogenomics: progress and obstacles toward the goal.

PMID- 15729594
TI  - Cancer pharmacogenomics: international trends.
AB  - It is well known that inter-individual variability exists in the responses to
      many drugs. Many nongenetic factors, such as age, sex, diet, and organ function,
      are known to affect the therapeutic effects of drugs. However, recent advances in
      pharmacogenomics have revealed that genetic polymorphisms also significantly
      influence both the efficacy and the toxicity of drugs. Mutations in the genes
      encoding drug-metabolizing enzymes, transporters, and target molecules may alter
      their expression, activity, or affinity to drugs, thereby influencing the drugs'
      pharmacokinetics and pharmacodynamics. Numerous studies have reported on the
      correlations between therapeutic outcomes and polymorphisms in drug-metabolizing
      enzymes, transporters, target molecules, and DNA repair enzymes. These
      pharmacogenomic discoveries are expected to be useful for the individualization
      and optimization of cancer chemotherapy.

PMID- 15729595
TI  - Cancer pharmacogenomics: achievements in basic research.
AB  - Pharmacogenomics is the study of how genetic inheritance influences the responses
      to drugs. Genetic polymorphisms in drug-metabolizing enzymes result in altered
      pharmacokinetics in therapeutic drugs. In recent years, there has been great
      progress in our knowledge of the effects of cytochrome P450 (CYP) polymorphisms
      on the pharmacokinetics of therapeutic drugs. CYP enzymes catalyze the activation
      or detoxification of several anticancer drugs. Anticancer drugs generally have a
      narrow therapeutic margin. Therefore, the interindividual variability in their
      efficacy and toxicity is a major problem in clinical practice. In this review,
      genetic polymorphisms of CYP enzymes and their clinical relevance in cancer
      chemotherapy are discussed.

PMID- 15729596
TI  - Squamous cell carcinoma of the bilharzial and non-bilharzial urinary bladder: a
      review of etiological features, natural history, and management.
AB  - Squamous cell carcinoma of the urinary bladder, though uncommon in Europe and the
      United States, is the most common variety of bladder tumor in countries where
      urinary bilharziasis prevails. A great controversy still exists regarding its
      natural history and management. Here, we review the literature of bilharzial and
      nonbilharzial squamous cell carcinoma of the urinary bladder, focusing on large
      series. Our aim was to gather most of the published data about this disease
      entity, report it in a systematic comparative review, and attempt to identify the
      adverse features and variables behind its dismal outcome. The conclusions are
      that squamous cell carcinoma, whether bilharzial or nonbilharzial, has
      distinctive clinicopathological features, different from those of the
      transitional cell variety. These tumors usually present in advanced (muscle
      invasive) stages. Pelvic nodal metastases are not common, and the incidence of
      distant metastases is less than that reported with transitional cell carcinoma.
      Local treatment, including cystectomy and adjunctive radiotherapy, is the most
      acceptable way of treating such tumors.

PMID- 15729597
TI  - Construction of a remote radiotherapy planning system.
AB  - BACKGROUND: We constructed a remote radiotherapy planning system, and we examined
      the usefulness of and faults in our system in this study. METHODS: Two identical
      radiotherapy planning systems, one installed at our institution and the other
      installed at an affiliated hospital, were used for radiotherapy planning. The two
      systems were connected by a wide area network (WAN), using a leased line. Beam
      data for the linear accelerator at the affiliated hospital were installed in the
      two systems. During the period from December 2001 to December 2002, 43 remote
      radiotherapy plans were made using this system. RESULTS: Data were transmitted
      using a file transfer protocol (FTP) software program. The 43 radiotherapy plans
      examined in this study consisted of 13 ordinary radiotherapy plans, 28
      radiotherapy plans sent to provide assistance for medical residents, and 2
      radiotherapy plans for emergency cases. There were ten minor planning changes
      made in radiotherapy plans sent to provide assistance for medical residents.
      CONCLUSION: Our remote radiotherapy planning system based on WAN using a leased
      line is useful for remote radiotherapy, with advantages for both radiation
      oncologists and medical residents.

PMID- 15729598
TI  - Clinicopathological features of prostate cancer in Japanese men diagnosed on
      repeat transrectal ultrasound-guided biopsy.
AB  - BACKGROUND: The objective of this study was to analyze the clinicopathological
      features of prostate cancer detected on repeat transrectal ultrasound-guided
      random biopsy in comparison with those detected on initial biopsy. METHODS:
      Between January 1999 and March 2004, 132 Japanese men underwent radical
      retropubic prostatectomy without neoadjuvant therapy at our institution. In 109
      patients (group A) prostate cancer was detected on initial biopsy, while in the
      remaining 23 (group B), it was diagnosed on repeat biopsy. We retrospectively
      characterized differences in clinicopathological features between these two
      groups. RESULTS: There were no significant differences in age, serum prostate
      specific antigen (PSA) value, or biopsy Gleason score between groups A and B.
      However, prostate volume in group A was significantly smaller than that in group
      B, while PSA density, the percentage of positive biopsy cores, and the percentage
      of cancers in the biopsy set in group A were significantly higher than those in
      group B. Pathological examination of the radical prostatectomy specimens showed
      that there were no significant differences in the distribution of pathological T
      stage or in the Gleason score; or in the incidences of lymphatic invasion,
      vascular invasion, and perineural invasion between groups A and B. Despite there
      being a significantly larger tumor volume in the radical prostatectomy specimens
      in group A compared to that in group B, there was no significant difference in
      the incidence of insignificant disease between these two groups. CONCLUSION:
      These findings suggest that missing the cancer on the initial needle biopsy may
      be due to a small cancer focus in a large prostate; however, there were no
      significant differences in the final pathological features of prostate cancers
      detected on the initial and repeat biopsies, suggesting similar biological
      behaviors. Thus performance of a repeat biopsy in cases negative for malignancy
      on the initial biopsy is advocated. Missing prostate cancer on the initial biopsy
      may be due to a small cancer focus in a large prostate; however prostate cancers
      detected on initial and repeat biopsies may have similar biological behavior.

PMID- 15729599
TI  - Hypoxia correlates with angiogenesis in cervical cancers.
AB  - BACKGROUND: Tissue hypoxia stimulates the induction of the angiogenic substances
      vascular endothelial growth factor and erythropoietin in the locus of the tissue.
      We have previously demonstrated that erythropoietin promotes angiogenesis by
      binding to its receptor in the endothelial cells of uterine and ovarian
      malignancies. In the present study, we examined whether malignant uterine cervix
      tissue showed hypoxia and whether hypoxia correlated with high vascular density
      through vascular endothelial growth factor. METHODS: To detect tissue hypoxia, we
      estimated the content of ATP in squamous cell carcinoma of the uterine cervix and
      in the normal cervix, using liquid chromatography columns. Surgically resected
      samples were fixed in Zamboni solution and processed for immunohistochemical
      microscopy to identify the endothelial cells and the location of vascular
      endothelial growth factor, with the use of anti-factor VIII and anti-vascular
      endothelial growth factor165 antibody, respectively. The microvessels in a
      definite area were counted in sections of each specimen. RESULTS: Significantly
      lower ATP levels and significantly higher vascular density were seen in squamous
      cell carcinoma than in the controls (P<0.05). The microvessel number in relation
      to ATP content was significantly higher in squamous cell carcinoma than in the
      controls (P<0.001). Moreover vascular endothelial growth factor, the hyperplastic
      epithelium of the squamous cell carcinoma contained the immunoreactivity, with
      characteristic histopathological features suggesting retention of tissue fluid.
      CONCLUSION: Squamous cell carcinoma of the uterine cervix showed hypoxia which
      correlated with abundant vascularity. Vascular endothelial growth factor
      expressed in the hyperplastic epithelium appears to promote angiogenesis in
      squamous cell carcinoma of the uterine cervix.

PMID- 15729600
TI  - A phase I/II study of S-1 plus cisplatin in patients with advanced gastric
      cancer: 2-week S-1 administration regimen.
AB  - BACKGROUND: The combination of a new oral dihydropyrimidine dehydrogenase
      inhibitory fluoropyrimidine (S-1) and cisplatin (CDDP) is one of the most active
      chemotherapy regimens for gastric cancer. However, the optimum schedule for this
      combination has not yet been determined. This study was conducted to establish
      the maximum tolerated dose (MTD) and the recommended dose of CDDP when combined
      with 2-week S-1 administration, and to observe the safety and efficacy of the
      regimen as treatment for patients with advanced gastric cancer. METHODS: S-1 was
      administered orally at a dose of 80 mg/m2 per day for 2 weeks, followed by a 2
      week rest. CDDP was administered intravenously on day 8 of each course; the
      initial dose of CDDP was 60 mg/m2 and it was increased in 10-mg/m2 increments.
      Treatment was repeated every 4 weeks unless disease progression was observed.
      RESULTS: Eleven patients were enrolled. The main toxicities were leucopenia,
      neutropenia, nausea, and anorexia. These toxicities were not severe, and were
      reversible and manageable. The MTD for CDDP was established as 80 mg/m2, as 2 of
      5 (40%) patients developed dose-limiting toxicity (DLT) at this level. Therefore,
      the recommended dose of CDDP was determined to be 70 mg/m2. All 11 patients were
      evaluable for a response: 8 achieved a partial response and 1 had stable disease.
      The overall response rate was 73%. CONCLUSION: This regimen is considered to be
      generally well-tolerated and has substantial antitumor activity.

PMID- 15729601
TI  - Health-related quality of life and treatment outcomes for men with prostate
      cancer treated by combined external-beam radiotherapy and hormone therapy.
AB  - BACKGROUND: Health-related quality of life (HR-QOL) is important when considering
      the treatment options for prostate cancer. METHODS: From 1992 to 1998, 57
      patients were treated by radiotherapy plus hormone therapy (median age, 79 years;
      median prostate-specific antigen concentration, 15.0 ng/ml; median radiotherapy
      dosage, 60 Gy). General HR-QOL was measured by the European Organization for
      Research and Treatment of Cancer Prostate Cancer QOL Questionnaire, and a newly
      developed disease-specific QOL survey was used to assess urinary and bowel
      functions. QOL was also measured in a control group of patients admitted for
      prostate biopsy. RESULTS: The general HR-QOL scores in the radiation group ranged
      from 70.0 to 91.3, with sexual problems showing the lowest (i.e., worst) score
      (38.5). Compared with the control group, the scores in the radiation group were
      worse for physical function and sexual problems. For disease-specific QOL, the
      radiation group had worse urinary function than controls, but were more satisfied
      with their urinary function. There was no difference between the radiation group
      and controls in satisfaction with bowel function. When the control group was
      subdivided at into two groups: age 75 years or less, and age over 75 years, the
      QOL score in the radiation group was the same as that in the subgroup aged over
      75 years. In subgroups of the radiation patients, according to survey period,
      there was no difference between the first and last surveys in longitudinal HR-QOL
      evaluations. The 5- and 10-year overall survival rates were 67.6% and 41.6%,
      respectively, and the 5- and 10-year cause-specific survival rates were 97.9% and
      94.7%. CONCLUSION: The combination of radiotherapy and hormone therapy has a good
      outcome and patients do not experience poor HR-QOL, except for sexual problems.
      Moreover, the disease-specific QOL is good, especially for urinary bother.

PMID- 15729602
TI  - A Japanese phase I study of continuous oral capecitabine in patients with
      malignant solid tumors.
AB  - BACKGROUND: This study aimed to evaluate the tolerability and pharmacokinetics of
      capecitabine, given twice daily for 6 weeks without interruption, and to identify
      the maximum tolerated dose (MTD) and the suggested phase II schedule. METHODS:
      The initial dose of capecitabine was 251 mg/m2 twice daily, without interruption,
      and a dose escalation schedule was planned according to a modified Fibonacci
      scheme. Patients received oral capecitabine twice daily for at least 6 weeks
      unless grade 3 or 4 toxicity was observed. Blood and urine samples were collected
      for pharmocokinetic analysis on days 1 and 15. RESULTS: Sixteen patients with
      malignant solid tumors (seven breast, seven colorectal, and two gastric) were
      enrolled, all of whom were evaluable. Among 4 patients treated with capecitabine
      1255 mg/m2 twice daily, one experienced grade 4 hemorrhagic gastric ulcer and one
      experienced grade 3 skin toxicity. Consequently, this dose was defined as the
      MTD, and gastrointestinal and cutaneous effects were identified as dose-limiting
      toxicities. There was no grade 3/4 diarrhea at any dose level. There was also no
      grade 4 hematologic toxicity at doses below the MTD, and there were no treatment
      related deaths. Two patients with breast cancer had partial responses, at
      capecitabine doses of 502 mg/m2 and 1255 mg/m2, twice daily. Pharmacokinetic data
      show that high concentrations of doxifluridine (5'-DFUR) occur in tumor cells
      within 2 h after administration of capecitabine. CONCLUSION: The MTD of
      continuous oral capecitabine over 6 weeks was 1255 mg/m2 twice daily. Because of
      the higher occurrence of skin disorders reported in this study with a continuous
      treatment regimen, an intermittent treatment regimen of 828 mg/m2, administered
      twice daily for 3 weeks, followed by a 1-week rest period, was recommended for
      phase II studies. This regimen is being evaluated in phase II studies in Japanese
      patients with gastric, colorectal, and breast cancers.

PMID- 15729603
TI  - Granulocyte colony-stimulating factor-producing malignant pleural mesothelioma
      with the expression of other cytokines.
AB  - We report a 65-year-old man with malignant pleural mesothelioma that produced
      granulocyte colony-stimulating factor (G-CSF) and other cytokines. At the first
      presentation, the WBC count was 8600 cells/microl and C-reactive protein (CRP)
      was 0.6 mg/dl. Seventeen months later, the WBC count had increased to 53,600
      cells/microl (93% neutrophils) and CRP to 27.1 mg/dl. The serum concentration of
      G-CSF had increased to 36.0 pg/dl (normal range, <5.0 pg/dl), interleukin 1beta
      (IL-1beta) to 46.0 pg/dl (normal range, <10 pg/dl), and IL-6 to 197 pg/dl (normal
      range, <4.0 pg/dl). The patient died 19 months after the first presentation, and
      6 weeks after sudden leukocytosis. At autopsy, a diagnosis of malignant pleural
      mesothelioma was made. The tumor cells were positive for anti-human G-CSF,
      granulocyte-macrophage colony-stimulating factor, IL-1beta, and IL-6 antibodies.
      Malignant mesothelioma may produce G-CSF and other cytokines. Mesothelial cells
      may have the potential to produce G-CSF and other cytokines in the progress of
      malignant formation, and this may be a factor influencing the poor prognosis.

PMID- 15729604
TI  - Long-term survival following concurrent chemoradiotherapy in patients with non
      small-cell lung cancer with concomitant brain metastases only.
AB  - We report two patients with non-small-cell lung cancer (NSCLC) with concomitant
      metastases to the brain only who received chemotherapy with concurrent
      radiotherapy for the thoracic disease and brain disease, resulting in long-term
      survival. One patient was a 56-year-old woman who was diagnosed as having
      adenocarcinoma and showed T2N1 thoracic disease; the other patient was a 57-year
      old man diagnosed with squamous cell carcinoma who had T1N3 thoracic disease.
      Both patients demonstrated multiple metastases to the brain only. Chemotherapy,
      consisting of cisplatin (40 mg/m2) and docetaxel (40 mg/m2), was administered on
      days 1 and 8, with the drugs being given separately, and the chemotherapy was
      repeated every 4 weeks for up to three cycles. Whole-brain irradiation (2 Gy/day;
      total, 36 Gy) and thoracic irradiation (2 Gy/day; total, 60 Gy) were started on
      days 1 and 29, respectively. Toxicities encountered were manageable by
      conventional therapy. The concurrent chemoradiation therapy resulted in complete
      regression of the brain disease in both patients. Brain disease relapsed in the
      female patient, but it is being controlled by the administration of gefitinib.
      She has survived for 53 months since the start of treatment, without new
      metastatic lesions or relapse of the thoracic lesions. The male patient has
      survived for 37 months without new metastatic lesions or relapses. Concurrent
      chemoradiotherapy in which radiotherapy is applied to both the brain and thoracic
      lesions may be effective for patients with NSCLC with metastases to the brain
      only.

PMID- 15729605
TI  - The benefit of chemotherapy in a patient with multiple brain metastases and
      meningitis carcinomatosa from ovarian cancer.
AB  - We report on a 45-year-old patient with stage IIIc ovarian cancer, multiple brain
      metastases, and meningitis carcinomatosa. After three courses of initial
      chemotherapy, consisting of docetaxel and carboplatin, the patient underwent
      interval cytoreductive surgery, consisting of hyster-ectomy, bilateral salpingo
      oophorectomy, omentectomy, appendectomy, and retroperitoneal lymphadenectomy.
      Then five courses of the same chemotherapy were given as adjuvant treatment. At
      the completion of the primary therapy, she achieved a complete remission. Ten
      months after the completion of the initial treatment, multiple brain metastases
      with meningitis carcinomatosa were detected. After four courses of the same
      chemotherapy, she again had a complete response, confirmed by cranial enhanced
      magnetic resonance imaging (MRI), and she felt well, with relief from the
      debilitating neurologic symptoms for 4 months. After this 4 months, her disease
      recurred, with meningitis carcinomatosa, and she requested supportive care only.
      She died 4 months after this recurrence. Chemotherapy can help to prolong life
      for some patients with multiple brain metastases and meningitis carcinomatosa
      from ovarian cancer.

PMID- 15729606
TI  - Biochemical markers in the management of pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a severe disease usually diagnosed by
      echocardiography and further confirmed by right heart catheterisation. Follow-up
      under treatment consists in assessment of clinical signs, various types of
      exercise testing and repeated echocardiograms. Several molecules which can be
      measured in the blood or sometimes in other biological fluids are known to be
      elevated in PAH. The most extensively studied are members of the family of
      natriuretic peptides, uric acid, and products generated by nitric oxide activity.
      Due to the low prevalence of PAH and their suboptimal specificity, these
      potential markers are generally of modest positive predictive value which
      precludes their use as screening tools. However, some of them correlate
      significantly with prognosis, and thus, in conjunction with classical clinical
      and paraclinical parameters, they may be a further aid to clinical decision
      making for the specialist dealing with PAH patients.

PMID- 15729608
TI  - Value of a standard urinary dipstick test for detecting microalbuminuria in
      patients with newly diagnosed hypertension.
AB  - PRINCIPLES: Microalbuminuria may indicate target organ damage in hypertensive
      patients. However, testing for microalbuminuria is not yet consistently used in
      general practice. This may be partly due to a lack of data regarding the
      diagnostic value of practice-based dipstick testing in newly diagnosed
      hypertension. Objectives were to assess the diagnostic value of a standard
      dipstick test for urinary protein excretion. METHOD: 186 patients who had been
      newly diagnosed with hypertension were screened for microalbuminuria. A spot
      urine sample from each of the subjects was evaluated by using a standard dipstick
      test (Combur 10, Roche Diagnostics GmbH, Mannheim, Germany) in a primary care
      setting. The albumin/creatinine ratio was used as the "gold standard". RESULTS:
      Dipstick testing for protein was positive in 31 urine samples (16.7% of the test
      samples). The albumin/creatinine ratio was elevated in 33 samples (17.7% of the
      test samples). The sensitivity of detecting microalbuminuria was 26%, specificity
      89%, positive predictive value 45%, and the negative predictive was 88%. Repeated
      dipstick testing 48 hours after the initial testing in 40 randomly selected
      patients showed a good reproducibility (98%). CONCLUSIONS: In a primary care
      setting a positive standard dipstick test of a random spot urine in patients with
      newly diagnosed hypertension may indicate the presence of microalbuminuria with
      high specificity. However, because of its low sensitivity, the standard urinary
      dipstick test can not be recommended as the sole method of screening for renal
      target organ damage. In addition standard dipstick testing is important to
      exclude confounding factors that can falsify the measurement of urinary protein
      excretion.

PMID- 15729607
TI  - Homelessness among people with severe mental illness in Switzerland.
AB  - QUESTIONS UNDER STUDY: This study addresses socio-demographic and clinical
      characteristics among homeless people in Switzerland admitted to inpatient care,
      the use of and pathways to inpatient care by this group and, the extent to which
      psychiatric disorders contribute to the risk of homelessness. METHODS: Based on
      data of a psychiatric case register we analysed 16247 people consecutively
      referred to psychiatric hospitals of a catchment area in Switzerland between 1998
      and 2001. RESULTS: 1.6% of all admitted patients (N = 257) were homeless (mean
      age: 34.4 years; women: 30.0%). The homeless as compared to other psychiatric
      inpatients had higher rates of substance use disorders, equal rates of psychotic
      and personality disorders, but lower rates of organic and affective disorders.
      Homeless people were more often compulsorily or as an emergency admitted. General
      practitioners (GPs) were less involved in the admission. The homeless had a
      shorter inpatient stay and their health status did not equally improve like in
      other patients. Risk factors of being homeless at psychiatric admission were:
      young age, male gender, single, low education level, urban residence, abuse of
      illicit drugs, especially multiple substance use, and having a dual diagnosis.
      CONCLUSIONS: Social factors and psychopathology are independently contributing to
      the risk of homelessness. Health care inequalities were found with regard to
      pathways to inpatient care (high rate of compulsory and emergency admissions, low
      involvement of GPs) and hospital stay (shorter stay, less improvement). Compared
      to other countries, disproportionate use of inpatient resources by homeless
      people could not be confirmed.

PMID- 15729609
TI  - Echocardiographic quantification of atherosclerosis leads to cost-effective
      treatment with statins.
AB  - OBJECTIVE: Use of statins in prevention of atherosclerosis is effective but
      expensive. Patient selection gains wider public attention as medication costs in
      the US and Europe augment by 8% to 10% per year. We examined different clinical
      risk stratification strategies, particularly focusing on echocardiographic
      atherosclerosis quantification, for their impact on event reduction and cost
      effectiveness in statin treatment. METHODS AND RESULTS: In a prospective,
      consecutive cohort of 336 patients referred to non-invasive cardiac examination,
      risk stratification was done by various combinations of risk factors and
      noninvasive atherosclerosis quantification. Atherosclerotic burden was determined
      through measuring "aortic elastance" by transthoracic echocardiogram, a validated
      non-invasive method. Cardiovascular events were recorded at a mean follow-up of
      one year. Echocardiographically determined atherosclerosis severity and event
      history, especially in combination, yielded the best selection strategies for
      statin treatment over a broad range of predetermined funding or required event
      reductions, surpassing conventional cardiovascular risk factors. From 26.8 statin
      preventable events/1000 patients/year (assuming all patients treated), the best
      selection strategies could avoid: 24 with 66% of the cost for statin treatment
      (atherosclerosis and age criteria), 20.1 with <50% of the budget, 12.2 with <30%
      of the budget or 9.6 with <15% of the budget (using combinations of
      atherosclerosis and prior events), while conventional strategies without echo
      quantification of atherosclerosis were inferior. CONCLUSION: Non-invasive
      echocardiographic quantification of atherosclerosis improves efficiency and cost
      effectiveness in statin treatment.

PMID- 15729610
TI  - Pulmonary rehabilitation in Switzerland.
AB  - Pulmonary rehabilitation is a form of therapy for patients with chronic lung
      disease that is evidence based, which ameliorates performance and endurance of
      the patient and improves quality of life significantly. Pulmonary rehabilitation
      also diminishes the amount of hospitalisations and the duration of stay in
      hospitals. It can improve capacity of work and diminishes the absenteeism.
      Motivated patients who have stopped or intend to stop smoking are the best
      candidates for a pulmonary rehabilitation programme.

PMID- 15729611
TI  - Co-morbidity and physician use in fibromyalgia.
AB  - OBJECTIVE: To describe comorbidity in women with FM, and to examine the effects
      of different types of comorbidity on physician use. METHODS: Women (n = 180) with
      primary FM were evaluated at baseline and 6 months later for self-reported health
      resource use and covariates. Reported comorbidity was classified into 4
      categories: medical, psychiatric, "functional", and unknown. The category for
      "functional" conditions included disorders that have been classified by previous
      authors as medically unexplained symptoms such as the irritable bowel and chronic
      fatigue syndromes. Logistic regression models were developed to examine
      associations between types of comorbidity and physician use. RESULTS: Comorbid
      conditions were reported by over 90% of the sample. Total number of comorbid
      complaints was associated with high number of physician visits. In logistic
      regression models (controlling for age, ethnicity, education, disability, pain,
      and psychological vulnerability) medical comorbidity was a much stronger
      determinant of high number of physician visits than was "functional" comorbidity.
      CONCLUSIONS: Comorbidity with other disorders, both functional and medical, was
      high in this sample. Medical and psychiatric comorbidity were stronger
      determinants of high physician use than "functional" comorbidity.

PMID- 15729612
TI  - How do patients define "good" and "bad" doctors?
AB  - QUESTIONS UNDER STUDY: Knowledge of hospital patients' perceptions of doctors'
      qualities is limited. The purpose of this study was to explore hospital patients'
      definitions of "good" and "bad" doctors. METHODS: Semi-structured interviews
      conducted with 68 consecutive hospital patients. The questions explored the
      characteristics of good/bad doctors. Responses were subjected to content
      analysis. RESULTS: The patients' mean age was 72.7 (+/- 15) years; 61% were
      female. Content analysis produced 9 categories connoted positively/negatively;
      the mean number of categories/patient response was 2.4 (+/- 1.3), ranging from 1
      6. Sensitivity/insensitivity to feelings were in the forefront, together with the
      importance of the relational dimension and the need to provide treatment tailored
      to the patient's needs. Patients' responses emphasised "bad" doctors' use of
      medicine as self-serving and not serving the patient. CONCLUSION: This
      qualitative enquiry made it possible to gather information on the patients'
      expectations or beliefs outside physicians' or health researchers' pre
      established categories. It emphasised that acknowledging possible areas of
      uncertainty may be less threatening for the doctor's image than exhibiting
      scientific proficiency unadapted to the patient's expectations and needs.

PMID- 15729613
TI  - Intussusception as a cause of bowel obstruction in adults.
AB  - BACKGROUND: Due to its unspecific presentation, intussusception is often
      diagnosed with delay in adults. METHODS: From 1986 to 2002, ten patients
      (men/women: 8/2, median age: 53.6 years) were managed for intussusception.
      Clinical, radiological and surgical management data were retrospectively
      analyzed. RESULTS: All patients presented with abdominal symptoms (pain: 10/10,
      nausea and vomiting: 3/10, diarrhoea: 2/10, "red-currant jelly stool": 2/10)
      during a median time of 8.3 months (2 days - 6 years) and with a trend for longer
      duration of symptoms for benign compared to malignant underlying disease (2 years
      vs 1 month). Two cases had developed acute bowel obstruction at the time of
      surgery. CT-scan was always performed, with correct diagnosis in seven cases.
      Ultrasonography (4/10), contrast enema (5/10) or coloscopy (4/10) either missed
      the intussusception or served merely to confirm the CT diagnosis. At surgery, an
      underlying lesion (six malignant and four benign tumours) was identified and
      removed in all cases (four small bowel, three right colon, two ileocaecal and one
      left colon resections). Eight were undiagnosed previously. CONCLUSIONS:
      Intussusception is rare in adults, but should be considered in cases of chronic
      or acute bowel obstructions. Early surgical management allows detection and
      potential cure of underlying tumours.

PMID- 15729614
TI  - Work-hours regulations in the European Union and their impact on the physician
      workforce.

PMID- 15729615
TI  - Anal lesions and suspected sexual abuse in a 17-year-old girl.

PMID- 15729616
TI  - Implication of cyclic nucleotide phosphodiesterase inhibition in the vasorelaxant
      activity of the citrus-fruits flavonoid (+/-)-naringenin.
AB  - The potential vasorelaxant, antioxidant and cyclic nucleotide phosphodiesterase
      (PDE) inhibitory effects of the citrus-fruit flavonoids naringin and (+/-)
      naringenin were comparatively studied for the first time in this work. (+/-)
      Naringenin (1 microM - 0.3 mM) did not affect the contractile response induced by
      okadaic acid (OA, 1 microM). However, (+/-)-naringenin relaxed, in a
      concentration-dependent manner, the contractions elicited by phenylephrine (PHE,
      1 microM) or by a high extracellular KCl concentration (60 mM) in intact rat
      aortic rings. Mechanical removal of endothelium and/or pretreatment of aorta
      rings with glibenclamide (GB, 10 microM) or tetraethylammonium (TEA, 2 mM) did
      not significantly modify the vasorelaxant effects of this flavanone. (+/-)
      Naringenin (10 microM - 0.1 mM) did not alter the basal uptake of 4) Ca2+ but
      decreased the influx of 45Ca2+ induced by PHE and KCl in endothelium-containing
      and endothelium-denuded rat aorta. (+/-)-Naringenin (10 microM - 0.1 mM) was
      ineffective to scavenge superoxide radicals (O*2-) generated by the hypoxanthine
      (HX)-xanthine oxidase (XO) system and/or to inhibit XO activity. (+/-)-Naringenin
      (0.1 mM) significantly increased the production of cGMP and cAMP decreased by PHE
      (1 microM) and high KCl (60 mM) in cultured rat aortic myocytes. (+/-)-Naringenin
      preferentially inhibited calmodulin (CaM)-activated PDE1, PDE4 and PDE5 isolated
      from bovine aorta with IC50 values of about 45 microM, 60 microM and 68 microM,
      respectively. In contrast, the 7-rhamnoglucoside of (+/-)-naringenin, naringin (1
      microM - 0.3 mM), was totally inactive in all experiments. These results indicate
      that the vasorelaxant effects of (+/-)-naringenin seem to be basically related to
      the inhibition of PDE1, PDE4 and PDE5 activities.

PMID- 15729617
TI  - Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia
      rebaudiana.
AB  - We have studied the effects of stevioside on the glucose and insulin metabolism
      in 2 models of diabetes in rats, STZ-induced diabetic rats and NIDDM diabetic
      rats induced by feeding with fructose. Stevioside (0.5 mg/kg), lowered the blood
      glucose levels in STZ-induced diabetic rats, peaking at 90 min. Stevioside
      administered twice daily also demonstrated dose-dependent effects in lowering the
      glucose levels in both diabetic rat models. Stevioside reduced the rise in
      glucose during glucose tolerance testing in normal rats. Stevioside dose
      dependently decreased protein levels of phosphoenol pyruvate carboxykinase
      (PEPCK) and PEPCK mRNA after 15 days of treatment. Stevioside also reduced
      insulin resistance in the diabetic animals as shown by the glucose lowering
      effects of tolbutamide. In conclusion, stevioside was able to regulate blood
      glucose levels by enhancing not only insulin secretion, but also insulin
      utilization in insulin-deficient rats; the latter was due to decreased PEPCK gene
      expression in rat liver by stevioside's action of slowing down gluconeogenesis.
      Further studies of this agent for the treatment of diabetes appear warranted.

PMID- 15729618
TI  - New estrogenic prenylflavone from Epimedium brevicornum inhibits the growth of
      breast cancer cells.
AB  - Estrogens maintain female sexual health. The hormone also drives the growth of
      estrogen receptor (ER) positive breast tumors, and ER modulators, like tamoxifen,
      are used to reduce tumor recurrence. To identify phytoestrogens with possible
      health benefits, we screened several Traditional Chinese Medicines and
      encountered an extract from the leaves of Epimedium brevicornum (EB), with strong
      (EC50: 1.3 microg/mL) and specific ER-stimulatory activity. It increased estrogen
      responsive human breast cancer cell proliferation at low doses, but paradoxically
      caused profound inhibition of growth at higher doses. Using bioassay-guided
      fractionation, we isolated and characterized a new prenylflavone, breviflavone B,
      which exerted biphasic stimulatory and inhibitory effects on breast cancer cell
      proliferation, mimicking the effects of EB. In contrast to estradiol and
      genistein, high doses (> 2 microM) of breviflavone B almost eliminated ERalpha
      protein; a process that may be mediated through increased proteasome degradation.
      Pre-clinical studies are needed to explore whether these prenylflavones are of
      value in estrogen-deficiency states and for prophylaxis of breast cancer.

PMID- 15729619
TI  - Further studies on a mixture of fatty acids from sugar cane (Saccharum
      officinarum) wax oil in animal models of hypersensitivity.
AB  - A mixture of fatty acids obtained from sugar cane wax oil, the main components of
      which are palmitic, oleic, linoleic and linolenic acids, was evaluated topically
      in two experimental models of hypersensitivity: the ear swelling response to
      ovalbumin in sensitized mice (ED50 edema: 0.63 +/- 0.06 mg/ear, ED50
      myeloperoxidase: 0.56 +/- 0.04 mg/ear, ED50 degranulated cells: 0.70 +/- 0,08
      mg/ear) and oxazolone-induced contact hypersensitivity in mice (ED50 edema: 1.63
      +/- 0.26 mg/ear, ED50 myeloperoxidase: 1.50 +/- 0.28 mg/ear, ED50 degranulated
      cells: 1.69 +/- 0.08 mg/ear). Also, the effect of this mixture was studied on the
      chemotaxis induced by fmlp (ED50: 25 +/- 3 microg/mL). The mixture showed anti
      inflammatory activity in both in vivo models of allergy and in the chemotaxis
      test. Therefore, these results provide evidence about the potential usefulness of
      the mixture of fatty acids from sugar cane wax oil in cutaneous inflammatory and
      allergic disorders.

PMID- 15729620
TI  - Isoliquiritigenin inhibits cell proliferation and induces apoptosis in human
      hepatoma cells.
AB  - Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is a natural pigment with a
      simple chalcone structure. In this study, we report the ISL-induced inhibition on
      the growth of human hepatoma cells (Hep G2) for the first time. The cell growth
      inhibition achieved by ISL treatment resulted in programmed cell death in a
      caspase activation-dependent manner, with an IC50 of 10.51 microg/mL. Outcomes of
      ISL treatment included the up-regulation of IkappaBalpha expression in the
      cytoplasm, and the decrease of NF-kappaB level as well as its activity in the
      nucleus. In addition, ISL also suppressed the expression of Bcl-XL and c-IAP1/2
      protein, the downstream target molecule of NF-kappaB. These results demonstrated
      that ISL treatment inhibited the NF-kappaB cell survival-signaling pathway and
      induced apoptotic cell death in Hep G2 cells.

PMID- 15729621
TI  - Inhibitory activity of a green tea extract and some of its constituents on
      multidrug resistance-associated protein 2 functionality.
AB  - Green tea extracts (GTE) might modulate ABC transporter gene expression or
      function. This may be relevant in the treatment of cancer or in influencing
      intestinal drug permeability. To gain more insight on the influence of a GTE on
      secretory transport proteins we investigated the influence of GTE and several
      green tea components on the mRNA expression level of P-glycoprotein (P-gp) and
      multidrug resistance-associated protein 2 (MRP2) in human gastrointestinal
      epithelial LS-180 cells. Furthermore, the functional activity of MRP2, using
      glutathione methylfluorescein (GS-MF) or [3H]methotrexate (MTX) as substrate, was
      investigated in canine kidney cells stably overexpressing human MRP2 (MDCK-MRP2).
      GTE, at a concentration of 0.01 mg/mL, did not increase mRNA expression of P-gp
      or MRP2 in LS-180 cells. Functional assays in MDCK-MRP2 cells using GS-MF did not
      show any effect of 0.01 mg/mL GTE on MRP2 activity. In the same cell line the
      cellular accumulation of MTX (a specific substrate of MRP2) was significantly
      increased with the MRP-specific inhibitor MK-571 or with 1 mg/mL GTE, but not
      with 0.1 mg/mL. The green tea components (-)-epigallocatechin gallate, (-)
      epigallocatechin, theanine, or caffeine, each in corresponding concentrations to
      the respective concentration of GTE, did not show any effect on MRP2 function.
      These data demonstrate that the mRNA expression patterns of P-gp and MRP2 in LS
      180 cells are not altered by 0.01 mg/mL of GTE. However, MRP2 function was
      inhibited by 1 mg/mL GTE, whereas none of the green tea components tested were
      responsible for this effect.

PMID- 15729622
TI  - Synthesis, in vitro, reactivity, and identification of 6-phenyl-3-hexen-2-one in
      human urine after kava-kava (Piper methysticum) ingestion.
AB  - This study describes the synthesis of 6 -phenyl-3-hexen-2-one, a proposed
      metabolite of kava-kava (kava, 'Awa, Yaqona, Piper methysticum Forst.), its
      reactivity with glutathione in vitro, and its isolation and identification, as
      its mercapturic acid adduct using LC/MS/MS, in the urine of two human subjects
      following their ingestion of kava. A possible metabolic pathway for the formation
      of this metabolite and its possible role in hepatotoxicity are also discussed.

PMID- 15729623
TI  - Urinary excretion of arbutin metabolites after oral administration of bearberry
      leaf extracts.
AB  - An HPLC assay with fluorimetric detection of the arbutin metabolites hydroquinone
      glucuronide (2) and hydroquinone sulphate (6) in urine was developed and
      validated. Methylarbutin (4) and 6 were synthesised as reference substances.
      Compound 2 was prepared enzymatically from hydroquinone and uridine 5'
      diphosphoglucuronic acid using the glucosyltransferase system of rat liver
      microsomes and enriched by two liquid-liquid and an additional solid phase
      extraction. Compound 2 as the main component of this purified product was
      identified by UV and fluorescence spectroscopy, by HPLC-MS, and by enzymatic
      hydrolysis to hydroquinone (5). The assay yields precise and accurate urine
      levels of 2, 5 and 6 in the concentration range expected after oral
      administration of recommended therapeutic doses of bearberry leaf extract. In a
      preliminary pharmacokinetic study on 3 volunteers the time-dependent renal
      excretion of arbutin metabolites 2, 5 and 6 was investigated after ingestion of
      an aqueous bearberry leaf extract containing an arbutin dose recommended by the
      German Kommission E. More than half of the administered dose of arbutin was
      excreted within 4 hours mainly in form of the metabolites 2 and 6 and more than
      75 % of the total applied arbutin was excreted within 24 h. The elimination of 5
      was negligible in 2 out of 3 volunteers. The excretion of this metabolite in the
      third test person reached 5.6 % of the total administered arbutin dose. The
      preliminary pharmacokinetic results confirm that renal elimination of
      toxicologically critical concentrations of the metabolite 5 will not be expected.

PMID- 15729624
TI  - Digoniodiol, deoxygoniopypyrone A, and goniofupyrone A: three new styryllactones
      from Goniothalamus amuyon.
AB  - Three new styrylpyrone analogues, digoniodiol (2), deoxygoniopypyrone A (3), and
      goniofupyrone A (4), along with ten known styryllactones, were isolated from the
      aerial parts of Goniothalamus amuyon. Among these compounds, 2 is the first
      example of a bis-styrylpyrone. Compound 4 represents a new skeleton for
      styryllactones. All structures were established on the basis of spectroscopic
      data. The stereochemistry of 2 and 4 was determined by X-ray crystallographic
      analysis. The absolute configuration of 3 and 4 was further confirmed by Mosher
      ester derivatives. All styryllactones were subjected to cytotoxicity assays.
      Among them, goniothalamin, goniothalamin epoxide, and 8-chlorogoniodiol showed
      significant cytotoxicity against the HepG2 cancer cell line with IC50 in the
      range of 0.19 - 0.64 microg/mL, and moderate activity toward Hep3B, MDA-MB-231,
      and MCF-7 cancer cell lines.

PMID- 15729625
TI  - New aromatic compounds from the marine mangrove Bruguiera gymnorrhiza.
AB  - The phytochemical investigation of the stem of Bruguiera gymnorrhiza yielded five
      new aromatic compounds (1-5), of which the bruguierols A - C (1-3) represent a
      new structural skeleton in natural product chemistry. All structures have been
      determined by NMR spectroscopic studies. Among them, 3 showed moderate activity
      against Gram-positive and Gram-negative bacteria including mycobacteria and
      resistant strains (MICs 12.5 microg/mL).

PMID- 15729626
TI  - Antibacterial caged-tetraprenylated xanthones from the stem bark of Garcinia
      scortechinii.
AB  - Five new caged-tetraprenylated xanthones, scortechinones L - P (1-5), together
      with six known scortechinones (A, B, D, F, I and J) and one known xanthone, 4
      '',5 ''-dihydro-1,5-dihydroxy-6 ',6 '-dimethylpyrano(2 ',3 ':6,7)-4 '',4 '',5 ''
      trimethylfurano(2 '',3 '':3,4)- xanthone, were isolated from the crude methanol
      extract of the stem bark of Garcinia scortechinii. The structures were elucidated
      by analysis of spectroscopic data and comparison of the NMR data with those
      reported previously. The antibacterial activity of all caged-polyprenylated
      xanthones, isolated from the latex and stem bark of G. scortechinii, was
      evaluated. Scortechinone B (6) exhibited significant antibacterial activity
      against a methicillin-resistant Staphylococcus aureus strain with an MIC value of
      2 microg/mL. From the MIC values, some structure-antibacterial activity
      relationships were established.

PMID- 15729627
TI  - Antitubercular constituents from the roots of Engelhardia roxburghiana.
AB  - Three new compounds, engelhardione, (-)-5-hydroxy-4-methoxy-1-tetralone, and 3
      methoxycarbonyl-1,5-dihydroxyanthraquinone, together with twelve known compounds
      have been isolated from the roots of Engelhardia roxburghiana. The structures of
      these new compounds were determined through spectral analyses. Engelhardione, 3
      methoxyjuglone, and (-)-4-hydroxy-1-tetralone showed antitubercular activities
      with MIC values=3.125, 3.125, and 6.25 microg/mL against Mycobacterium
      tuberculosis 90-221,387, respectively, and with MIC values=0.2, 0.2, and 4.0
      microg/mL against M. tuberculosis H37Rv, individually.

PMID- 15729628
TI  - Miniaturization of the structure elucidation of novel natural products--two trace
      antibacterial acylated caprylic alcohol glycosides from Arctostaphylos pumila.
AB  - High-throughput isolation, purification and analysis methods applied to natural
      products libraries from plants gave rise to the discovery of two novel acylated
      caprylic alcohol glycosides (1, 2) produced by Arctostaphylos pumila. The NMR
      spectra were acquired using the CapNMR probe and performed on mass-limited
      samples, which enabled us to elucidate the structures of 2,6-diacetyl-3,4
      diisobutyl-1- O-octylglucopyranoside (1, 200 microg) and 2,6-diacetyl-3,4
      dimethylbutyl-1- O-octylglucopyranosid (2, 70 microg). Compounds 1 and 2
      exhibited antibacterial activity against Gram-positive methicillin-resistant
      Staphylococcus aureus with an MIC of 128 microg/mL and 64 microg/mL,
      respectively.

PMID- 15729629
TI  - Cytotoxic constituents from Cratoxylum arborescens.
AB  - A new natural xanthone, 1,3-dihydroxy-6,7-dimethoxy-2,8-diprenylxanthone,
      together with four known compounds, fuscaxanthone C, 1,7-dihydroxyxanthone, 3
      geranyloxy-6-methyl-1,8-dihydroxyanthraquinone and 2-geranylemodin were isolated
      from the stem bark of Cratoxylum arborescens (Vahl) Blume. The structure
      elucidations were achieved through spectroscopic analyses. Compounds 1 and 5
      showed moderate activity against the human small cell lung cancer NCI-H187 cell
      line with the IC50 values of 3.69 +/- 1.27 microg/mL and 3.08 +/- 0.73 microg/mL,
      respectively.

PMID- 15729630
TI  - Hypouricemic action of scopoletin arising from xanthine oxidase inhibition and
      uricosuric activity.
AB  - Scopoletin exhibited an immediate and dose-dependent hypouricemic effect after
      intraperitoneal administration (50, 100, 200 mg/kg) in hyperuricemic mice induced
      by potassium oxonate; however, it did not affect the serum uric acid level in
      normal mice at the tested doses. For exploring the involved mechanisms of action
      of scopoletin, potential inhibitory effects on xanthine oxidase and possible
      uricosuric effects were investigated. Scopoletin (50, 100, 200 mg/kg)
      significantly inhibited the activity of xanthine oxidase in liver homogenates of
      hyperuricemic mice although it only showed a relatively weak, albeit competitive
      type, inhibition of xanthine oxidase in a commercial assay. Furthermore, a potent
      uricosuric effect of scopoletin (100, 200 mg/kg) was ascertained. These results
      demonstrated for the first time that scopoletin exhibits, hypouricemic activities
      through decreasing uric acid production and as well as a uricosuric mechanism.

PMID- 15729631
TI  - Chemical composition and antimicrobial activity of the essential oils of
      Artemisia scoparia and A. capillaris.
AB  - The chemical composition of the essential oils obtained from Artemisia scoparia
      Waldst. et Kitamura and Artemisia capillaris Thunb. was analyzed by GC/MS. The
      essential oil of A. scoparia was rich in camphor (11.0 %), 1,8-cineole (21.5 %),
      and beta-caryophyllene (6.8 %) as the major compounds, whereas A. capillaris oil
      was rich in beta-pinene (9.4 %), beta-caryophyllene (11.1 %), and capillene (32.7
      %). The essential oils and some of their major compounds were tested for their
      antimicrobial activity against 15 different genera of oral bacteria. The
      essential oils of A. scoparia and A. capillaris exhibited considerable inhibitory
      effects against all oral bacteria tested, while their major components
      demonstrated various degrees of growth inhibition.

PMID- 15729632
TI  - Combretastatins D-3 and D-4, new macrocyclic lactones from Getonia floribunda.
AB  - Chemical investigation of biologically active compounds of Getonia floribunda led
      to the isolation of two new macrocyclic lactones, combretastatins D-3 (1) and D-4
      (2). The structures of these compounds were confirmed by spectroscopic analyses.
      Combretastatin D-3 (1) exhibited cytotoxicity towards the small-cell lung cancer
      cell line (NCI-H187, IC50=13.0 +/- 0.2 microg/mL) but was inactive against KB, BC
      1, and Vero cell lines. Combretastatin D-3 (1) showed weak antitubercular
      activity with a minimum inhibitory concentration (MIC) of 100.0 microg/mL, and
      was inactive towards the malarial parasite. Combretastatin D-4 (2) was inactive
      in all antitubercular, antiplasmodial, and cytotoxic assays.

PMID- 15729633
TI  - Glaucopines A and B, new cyathane diterpenes from the fruiting bodies of Sarcodon
      glaucopus.
AB  - Glaucopine A (1) and B (2), two new cyathane diterpenes, have been isolated from
      the mushroom Sarcodon glaucopus: their structures have been determined on the
      basis of spectral data. Their topical anti-inflammatory activity was evaluated
      using the Croton oil ear test in mice: compounds 1 and 2 (1 micromol/cm2)
      provoked edema reduction (62 % and 55 %, respectively) similar to that induced by
      the reference non-steroidal anti-inflammatory drug, indomethacin (0.3
      micromol/cm2, 61 % edema reduction).

PMID- 15729634
TI  - Self-organization and vegetation collapse in salt marsh ecosystems.
AB  - Complexity theory predicts that local feedback processes may strongly affect the
      organization of ecosystems on larger spatial scales. Whether complexity leads to
      increased resilience and stability or to increased vulnerability and criticality
      remains one of the dominant questions in ecology. We present a combined
      theoretical and empirical study of complex dynamics in mineralogenic salt marsh
      ecosystems that emerge from a positive feedback between clay accumulation and
      plant growth. Positive feedback induces self-organizing within the ecosystem,
      which buffers for the strong physical gradient that characterizes the marine
      terrestrial boundary, and improves plant growth along the gradient. However, as a
      consequence of these self-organizing properties, salt marshes approach a critical
      state as the edge of the salt marsh and the adjacent intertidal flat becomes
      increasingly steep and vulnerable to wave attack. Disturbance caused, for
      instance, by a storm may induce a cascade of vegetation collapse and severe
      erosion on the cliff edge, leading to salt marsh destruction. Our study shows
      that on short timescales, self-organization improves the functioning of salt
      marsh ecosystems. On long timescales, however, self-organization may lead to
      destruction of salt marsh vegetation.

PMID- 15729635
TI  - A parametric model for estimation of dispersal patterns applied to five passerine
      spatially structured populations.
AB  - Natal dispersal capture-recapture data from five fragmented populations of house
      sparrows, great tits, and blue tits were analyzed using maximum likelihood
      methods. A new two-parametric distribution was constructed that includes four
      distributions previously used as special cases in the literature. Dispersal
      standard deviations were estimated at 22.9 km for the house sparrows and ranged
      from 0.66 to 4.4 km for the tits. Female great tits and blue tits dispersed
      consistently further than males. Estimates of the shape parameter of the
      dispersal distribution ranged from 0.66 to 2.27, indicating strong to moderately
      leptokurtic dispersal displacements. There were significant effects of density on
      local immigration rates and a consistent tendency for immigration rates to depend
      underproportionally on local densities. Potential implications of the shape of
      the dispersal distribution for the spread of invading organisms were investigated
      and compared with previous results. It is shown that the wave speed, for a given
      dispersal standard deviation, depends only to some extent on leptokurtosis,
      provided that the intrinsic growth rate of the population is moderate or small.
      In estimating the dispersal standard deviation, however, incorrect assumptions
      about the degree of leptokurtosis can lead to a large bias in estimation and
      predictions.

PMID- 15729636
TI  - Metabolic stoichiometry and the fate of excess carbon and nutrients in consumers.
AB  - Animals encountering nutritionally imbalanced foods should release elements in
      excess of requirements in order to maintain overall homeostasis. Quantifying
      these excesses and predicting their fate is, however, problematic. A new model of
      the stoichiometry of consumers is formulated that incorporates the separate terms
      in the metabolic budget, namely, assimilation of ingested substrates and
      associated costs, protein turnover, other basal costs, such as osmoregulation,
      and the use of remaining substrates for production. The model indicates that
      release of excess C and nonlimiting nutrients may often be a significant fraction
      of the total metabolic budget of animals consuming the nutrient-deficient forages
      that are common in terrestrial and aquatic systems. The cost of maintenance, in
      terms of not just C but also N and P, is considerable, such that food quality is
      important even when intake is low. Many generalist consumers experience short
      term and unpredictable fluctuations in their diets. Comparison of model output
      with data for one such consumer, Daphnia, indicates that mechanisms operating
      postabsorption in the gut are likely the primary means of regulating excess C, N,
      and P in these organisms, notably respiration decoupled from biochemical or
      mechanical work and excretion of carbon and nutrients. This stoichiometrically
      regulated release may often be in organic rather than inorganic form, with
      important consequences for the balance of autotrophic and heterotrophic processes
      in ecosystems.

PMID- 15729637
TI  - Should models of disease dynamics in herbivorous insects include the effects of
      variability in host-plant foliage quality?
AB  - Interactions between insects and their baculovirus pathogens are often described
      using simple disease models. Baculoviruses, however, are transmitted when insects
      consume virus-contaminated foliage, and foliage variability, whether within or
      between host-plant species, can affect viral infectiousness. Insect-baculovirus
      interactions may thus be embedded in a tritrophic interaction with the insect's
      host plant, but disease models include only the host and the pathogen. We tested
      these models by measuring the transmission of a baculovirus of gypsy moths
      (Lymantria dispar) on red oak (Quercus rubra) and white oak (Quercus alba) in the
      field in six experiments over four years. In all experiments, there were only
      weak effects of host-tree species, and in only one did the best-fitting model
      include tree species effects. These weak effects of foliage variability on
      transmission were not due to a lack of foliage variability on viral
      infectiousness, because when larvae were force-fed virus-contaminated foliage,
      infection rates were higher on white oak. Our results suggest that feeding
      behavior plays an important role in baculovirus transmission and that models can
      usefully describe baculovirus dynamics even without including foliage
      variability. Our work provides a clear example of how two-species models are
      sometimes sufficient to describe what appear to be tritrophic interactions.

PMID- 15729638
TI  - Phenotypic divergence along lines of genetic variance.
AB  - Natural populations inhabiting the same environment often independently evolve
      the same phenotype. Is this replicated evolution a result of genetic constraints
      imposed by patterns of genetic covariation? We looked for associations between
      directions of morphological divergence and the orientation of the genetic
      variance-covariance matrix (G) by using an experimental system of morphological
      evolution in two allopatric nonsister species of rainbow fish. Replicate
      populations of both Melanotaenia eachamensis and Melanotaenia duboulayi have
      independently adapted to lake versus stream hydrodynamic environments. The major
      axis of divergence (z) among all eight study populations was closely associated
      with the direction of greatest genetic variance (gmax), suggesting directional
      genetic constraint on evolution. However, the direction of hydrodynamic
      adaptation was strongly associated with vectors of G describing relatively small
      proportions of the total genetic variance, and was only weakly associated with
      gmax. In contrast, divergence between replicate populations within each habitat
      was approximately proportional to the level of genetic variance, a result
      consistent with theoretical predictions for neutral phenotypic divergence.
      Divergence between the two species was also primarily along major eigenvectors of
      G. Our results therefore suggest that hydrodynamic adaptation in rainbow fish was
      not directionally constrained by the dominant eigenvector of G. Without
      partitioning divergence as a consequence of the adaptation of interest (here,
      hydrodynamic adaptation) from divergence due to other processes, empirical
      studies are likely to overestimate the potential for the major eigenvectors of G
      to directionally constrain adaptive evolution.

PMID- 15729639
TI  - Intrinsic scaling complexity in animal dispersion and abundance.
AB  - Ecological theory related to animal distribution and abundance is at present
      incomplete and to some extent naive. We suggest that this may partly be due to a
      long tradition in the field of model development for choosing mathematical and
      statistical tools for convenience rather than applicability. Real population
      dynamics are influenced by nonlinear interactions, nonequilibrium conditions, and
      scaling complexity from system openness. Thus, a coherent theory for individual-,
      population-, and community-level processes should rest on mathematical and
      statistical methods that explicitly confront these issues in a manner that
      satisfies principles from statistical mechanics for complex systems. Instead,
      ecological theory is traditionally based on premises from simpler statistical
      mechanical theory for memory-free, scale-specific, random-walk, and diffusion
      processes, while animals from many taxa generally express strategic homing, site
      fidelity, and conspecific attraction in direct violation of primary model
      assumptions. Thus, the main challenge is to generalize the theory for memory-free
      physical, many-body systems to include a more realistic memory-influenced
      framework that better satisfies ecological realism. We describe, simulate, and
      discuss three testable aspects of a model for multiscaled habitat use at the
      individual level: (1) scale-free distribution of movement steps under influence
      of self-reinforcing site fidelity, (2) fractal spatial dispersion of intra-home
      range relocations, and (3) nonasymptotic expansion of observed intra-home range
      patch use with increasing set of relocations. Examples of literature data
      apparently supporting the conjecture that multiscaled, strategic space use is
      widespread among many animal taxa are also described. We suggest that the present
      approach, which provides a protocol to test for influence from scale-free, memory
      dependent habitat use at the individual level, may also point toward a guideline
      for development of a generalized theoretical framework for complex population
      kinetics and spatiotemporal population dynamics.

PMID- 15729640
TI  - Evolution of dietary specialization and chemical defense in poison frogs
      (Dendrobatidae): a comparative analysis.
AB  - Defensive mechanisms, including noxious or toxic substances, are favored by
      predation-driven natural selection. The acquisition of noxious/toxic substances
      can be either endogenous, in which the substances are produced by the organism,
      or exogenous, in which the substances are produced by another organism and are
      sequestered. Evidence indicates that the defensive skin alkaloids of Neotropical
      poison frogs (Dendrobatidae) have an exogenous source: a diet of ants and other
      small alkaloid-containing arthropods, which we term the diet-toxicity hypothesis.
      A critical prediction of the diet-toxicity hypothesis is that independent origins
      of dietary specialization will be found to be correlated with independent origins
      of skin alkaloids. We tested this prediction in an integrated framework using
      comparative methods with new and published data on feeding ecology and chemical
      defense for 15 species of dendrobatids in five genera. We found a significant
      correlation between alkaloid profiles and degree of dietary specialization. This
      reveals a recurring association of dietary specialization and alkaloid
      sequestration in dendrobatids, which suggests parallel evolutionary trends in the
      origins of defensive mechanisms.

PMID- 15729641
TI  - Habitat size, recruitment, and longevity as factors limiting population size in
      stage-structured species.
AB  - Surprisingly little research has evaluated how habitat size may limit the
      population size of species that use different habitats at different stages of
      their lives. Here we develop simple discrete-time models to describe the
      population dynamics of species that use separate juvenile and adult habitats.
      Analytic solutions, model simulations, and elasticity and sensitivity analyses
      show that adult abundance is only limited by the size of the juvenile habitat
      when both adult habitat size and recruitment are much larger than juvenile
      habitat size. Juvenile habitat plays a marginally greater role in limiting
      population size for species with closed populations, where recruitment is
      proportional to adult abundance, versus open populations. Because adult
      populations often accumulate pulses of juveniles, adult habitat size can strongly
      limit population size over a broad range of parameter values, an effect that
      increases as the longevity of a species increases. Limited empirical research
      from a range of taxa supports these model predictions, although few studies were
      designed to actually test the limiting role of juvenile versus adult habitat.
      Future research must carefully evaluate whether and how processes at the juvenile
      stage affect adult abundance, and conservation efforts may be able to use this
      model to evaluate the cost-effectiveness, vis-a-vis increasing adult abundance,
      of time and money allocated to protecting juvenile habitats.

PMID- 15729642
TI  - Male "mixed" reproductive strategies in biparental species: Trivers was probably
      right, but why?
AB  - Trivers proposed that, if parental care by both sexes is advantageous, males
      should practice a "mixed" strategy of seeking extrapair copulations, while
      restricting their parental investment to offspring of social mates. We explore
      circumstances under which males should limit their parental care in the predicted
      manner. We find that Trivers's "mixed" strategy will generally be evolutionarily
      stable so long as either socially monogamous or polygynous males usually sire
      more offspring per brood from a social mate than they typically sire in broods of
      extrapair mates. Polygynous males should spread investment across their home
      nests unless the expected number of chicks sired in them differs widely. Whether
      polygynous males should restrict paternal care to social mates' offspring hinges
      additionally on resident male investment in broods containing extrapair young: if
      resident males contribute minimally, some investment by a polygynous extrapair
      male becomes more advantageous. Recently reviewed data on extrapair fertilization
      distributions within monogamous and polygynous passerines suggest that extrapair
      offspring often predominate numerically within their broods, consistent with
      sperm expenditure theory. Nevertheless, most species conform to the model's
      criterion regarding relative parentage levels in broods of social versus
      extrapair mates. Patterns of extrapair parentage thus appear sufficient to
      stabilize biparental care systems.

PMID- 15729643
TI  - Demographic theory of coral reef fish populations with stochastic recruitment:
      comparing sources of population regulation.
AB  - The effects of three forms of density-dependent regulation were explored in model
      coral reef fish populations: top-down (predation), bottom-up (competition for
      food), and pelagic (non-reef-based mechanisms) control. We describe the
      demographic responses of both biomass and numbers of adult fish, predicting the
      mean and the variance of temporal fluctuations resulting from stochastic
      recruitment of juveniles. We find that top-down control acts by suppressing
      variability of numbers of fish, which in turn suppresses the variability of
      biomass. Bottom-up control has no effect on fluctuations of numbers of fish,
      though it strongly reduces fluctuations of biomass. Because fecundity of fish is
      directly linked to body mass, the regulation of biomass tightly regulates
      reproductive output independently of the number of individuals in the population.
      Finally, populations under pelagic control experience bounded fluctuations of
      biomass and numbers directly proportional to the bounded fluctuations of
      recruitment. The demographic signatures predicted from both bottom-up and pelagic
      control are consistent with current evidence supporting the recruitment
      limitation hypothesis in reef fish ecology. We propose tests to discriminate the
      dominant mode of density-dependent regulation using qualitative trends in time
      series demographic data across environmental clines.

PMID- 15729644
TI  - Dispersal, eviction, and conflict in meerkats (Suricata suricatta): an
      evolutionarily stable strategy model.
AB  - Decisions regarding immigration and emigration are crucial to understanding group
      dynamics in social animals, but dispersal is rarely treated in models of optimal
      behavior. We developed a model of evolutionarily stable dispersal and eviction
      strategies for a cooperative mammal, the meerkat Suricata suricatta. Using rank
      and group size as state variables, we determined state-specific probabilities
      that subordinate females would disperse and contrasted these with probabilities
      of eviction by the dominant female, based on the long-term fitness consequences
      of these behaviors but incorporating the potential for error. We examined whether
      long-term fitness considerations explain group size regulation in meerkats;
      whether long-term fitness considerations can lead to conflict between dominant
      and subordinate female group members; and under what circumstances those
      conflicts were likely to lead to stability, dispersal, or eviction. Our results
      indicated that long-term fitness considerations can explain group size regulation
      in meerkats. Group size distributions expected from predicted dispersal and
      eviction strategies matched empirical distributions most closely when emigrant
      survival was approximately that determined from the field study. Long-term
      fitness considerations may lead to conflicts between dominant and subordinate
      female meerkats, and eviction is the most likely result of these conflicts. Our
      model is computationally intensive but provides a general framework for
      incorporating future changes in the size of multimember cooperative breeding
      groups.

PMID- 15729645
TI  - Alternative life-history pathways and the elasticity of stochastic matrix models.
AB  - Loop analysis is a powerful tool for analyzing matrix population models. This
      note shows that the results of loop analysis, which have been proved for constant
      matrices only, apply to stochastic matrices as well if elasticity is defined as
      the effect of a proportional perturbation of both mean and variance. Using the
      ideas of loop analysis, it is shown that the structure of the stochastic matrix
      in terms of alternative life-history pathways has important consequences for the
      effect of stochasticity on elasticities. If the life cycle contains
      nonoverlapping, alternative life-history pathways, the ranking in terms of
      elasticity of the most critical vital rates may be reversed in stochastic and the
      corresponding average environments. This has obvious and important consequences
      for population management because focusing on a deterministic model would lead to
      an ineffective or counterproductive management strategy.

PMID- 15729646
TI  - Assessing concordance of fossil calibration points in molecular clock studies: an
      example using turtles.
AB  - Although still controversial, estimation of divergence times using molecular data
      has emerged as a powerful tool to examine the tempo and mode of evolutionary
      change. Two primary obstacles in improving the accuracy of molecular dating are
      heterogeneity in DNA substitution rates and accuracy of the fossil record as
      calibration points. Recent methodological advances have provided powerful methods
      that estimate relative divergence times in the face of heterogeneity of
      nucleotide substitution rates among lineages. However, relatively little
      attention has focused on the accuracy of fossil calibration points that allow one
      to translate relative divergence times into absolute time. We present a new cross
      validation method that identifies inconsistent fossils when multiple fossil
      calibrations are available for a clade and apply our method to a molecular
      phylogeny of living turtles with fossil calibration times for 17 of the 22
      internal nodes in the tree. Our cross-validation procedure identified seven
      inconsistent fossils. Using the consistent fossils as calibration points, we
      found that despite their overall antiquity as a lineage, the most species-rich
      clades of turtles diversified well within the Cenozoic. Many of the truly ancient
      lineages of turtles are currently represented by a few, often endangered species
      that deserve high priority as conservation targets.

PMID- 15729647
TI  - The opportunity for canalization and the evolution of genetic networks.
AB  - There has been a recent revival of interest in how genetic interactions evolve,
      spurred on by an increase in our knowledge of genetic interactions at the
      molecular level. Empirical work on genetic networks has revealed a surprising
      amount of robustness to perturbations, suggesting that robustness is an evolved
      feature of genetic networks. Here, we derive a general model for the evolution of
      canalization that can incorporate any form of perturbation. We establish an upper
      bound to the strength of selection on canalization that is approximately equal to
      the fitness load in the system. This method makes it possible to compare
      different forms of perturbation, including genetic, developmental, and
      environmental effects. In general, load that arises from mutational processes is
      low because the mutation rate is itself low. Mutation load can create selection
      for canalization in a small network that can be achieved through dominance
      evolution or gene duplication, and in each case selection for canalization is
      weak at best. In larger genetic networks, selection on genetic canalization can
      be reasonably strong because larger networks have higher mutational load. Because
      load induced through migration, segregation, developmental noise, and
      environmental variance is not mutation limited, each can cause strong selection
      for canalization.

PMID- 15729648
TI  - A source-sink hypothesis for abyssal biodiversity.
AB  - Bathymetric gradients of biodiversity in the deep-sea benthos constitute a major
      class of large-scale biogeographic phenomena. They are typically portrayed and
      interpreted as variation in alpha diversity (the number of species recovered in
      individual samples) along depth transects. Here, we examine the depth ranges of
      deep-sea gastropods and bivalves in the eastern and western North Atlantic. This
      approach shows that the abyssal molluscan fauna largely represents deeper range
      extensions for a subset of bathyal species. Most abyssal species have larval
      dispersal, and adults live at densities that appear to be too low for successful
      reproduction. These patterns suggest a new explanation for abyssal biodiversity.
      For many species, bathyal and abyssal populations may form a source-sink system
      in which abyssal populations are regulated by a balance between chronic
      extinction arising from vulnerabilities to Allee effects and immigration from
      bathyal sources. An increased significance of source-sink dynamics with depth may
      be driven by the exponential decrease in organic carbon flux to the benthos with
      increasing depth and distance from productive coastal systems. The abyss, which
      is the largest marine benthic environment, may afford more limited ecological and
      evolutionary opportunity than the bathyal zone.

PMID- 15729650
TI  - Coexistence of cycling and dispersing consumer species: Armstrong and McGehee in
      space.
AB  - Two competing consumer species may coexist using a single homogeneous resource
      when the more efficient consumer--the one having the lowest equilibrium resource
      density--has a more nonlinear functional response that generates consumer
      resource cycles. We extend this model of nonequilibrium coexistence, as proposed
      by Armstrong and McGehee, by putting the interaction into a spatial context using
      two frameworks: a spatially explicit individual-based model and a spatially
      implicit metapopulation model. We find that Armstrong and McGehee's mechanism of
      coexistence can operate in a spatial context. However, individual-based
      simulations suggest that decreased dispersal restricts coexistence in most cases,
      whereas differential equation models of metapopulations suggest that a low rate
      of dispersal between subpopulations often increases the coexistence region. This
      difference arises in part because of two potentially opposing effects on
      coexistence due to the asynchrony in the temporal dynamics at different
      locations. Asynchrony implies that the less efficient species is more likely to
      be favored in some spatial locations at any given time, which broadens the
      conditions for coexistence. On the other hand, asynchrony and dispersal can also
      reduce the amplitude of local population cycles, which restricts coexistence. The
      relative influence of these two effects depends on details of the population
      dynamics and the representation of space. Our results also demonstrate that
      coexistence via the Armstrong-McGehee mechanism can occur even when there is
      little variation in the global densities of either the consumers or the resource,
      suggesting that empirical studies of the mechanisms should measure densities on
      several spatial scales.

PMID- 15729649
TI  - Determinants of species richness in the Park Grass Experiment.
AB  - The Park Grass Experiment at Rothamsted in southeast England was started in 1856,
      making it the longest-running experiment in plant ecology anywhere in the world.
      Experimental inputs include a range of fertilizers (nitrogen, phosphorus,
      potassium, and organic manures) applied annually, with lime applied occasionally,
      and these have led to an increase in biomass and, where nitrogen was applied in
      the form of ammonium sulfate, to substantial decreases in soil pH. The number of
      species per plot varies from three to 44 per 200 m(2), affording a unique
      opportunity to study the determinants of plant species richness and to estimate
      the effect sizes attributable to different factors. The response of species
      richness to biomass depends on the amount and type of nitrogen applied; richness
      declined monotonically with increasing biomass on plots receiving no nitrogen or
      receiving nitrogen in the form of sodium nitrate, but there was no relationship
      between species richness and biomass on plots acidified by ammonium sulfate
      application. The response to lime also depended on the type of nitrogen applied;
      there was no relationship between lime treatment and species richness, except in
      plots receiving nitrogen in the form of ammonium sulfate, where species richness
      increased sharply with increasing soil pH. The addition of phosphorus reduced
      species richness, and application of potassium along with phosphorus reduced
      species richness further, but the biggest negative effects were when nitrogen and
      phosphorus were applied together. The analysis demonstrates how multiple factors
      contribute to the observed diversity patterns and how environmental regulation of
      species pools can operate at the same spatial and temporal scale as biomass
      effects.

PMID- 15729651
TI  - Adaptive evolution of social traits: origin, trajectories, and correlations of
      altruism and mobility.
AB  - Social behavior involves "staying and helping," two individual attributes that
      vary considerably among organisms. Investigating the ultimate causes of such
      variation, this study integrates previously separate lines of research by
      analyzing the joint evolution of altruism and mobility. We unfold the network of
      selective pressures and derive how these depend on physiological costs, eco
      evolutionary feedbacks, and a complex interaction between the evolving traits.
      Our analysis highlights habitat saturation, both around individuals (local
      aggregation) and around unoccupied space (local contention), as the key mediator
      of altruism and mobility evolution. Once altruism and mobility are allowed to
      evolve jointly, three general insights emerge. First, the cost of mobility
      affects the origin of altruism, determining whether and how quickly selfishness
      is overcome. Second, the cost of altruism determines which of two qualitatively
      different routes to sociality are taken: an evolutionary reduction of mobility,
      resulting in higher habitat saturation, is either preceded or followed by the
      adaptive rise of altruism. Third, contrary to conventional expectations, a
      positive correlation between evolutionarily stable levels of altruism and
      mobility can arise; this is expected when comparing populations that evolved
      under different constraints on mobility or that differ in other life-history
      traits.

PMID- 15729652
TI  - Flower color microevolution in wild radish: evolutionary response to pollinator
      mediated selection.
AB  - Evolutionary ecologists are fundamentally interested in how species interactions
      affect evolutionary change. We tested the degree to which plant-pollinator
      interactions affect the frequency of flower color morphs of Raphanus sativus.
      Petal color in R. sativus is determined by two independently assorting loci,
      producing four petal colors (yellow, white, pink, and bronze). We assessed the
      impact of pollinator discrimination on changes in flower color variation by
      comparing the frequency of colors produced in the presence (open pollination)
      versus absence (null pollination) of pollinator discrimination. We also assessed
      the impact of postpollination and developmental effects on progeny colors using
      equal pollinations with all four color morphs. Our results from open pollinations
      found an overrepresentation of yellow progeny in the next generation, when
      compared with both null pollinations and cumulative ratios based on Hardy
      Weinberg and linkage equilibria assumptions. When these results were combined
      with those from equal pollinations, the overrepresentation of yellow could be
      attributed to selection from pollinators. Yet, surveys in the field the following
      year found no flower color frequency changes in the next generation. These
      results illustrate that flower color microevolution can be driven by both
      pollinator discrimination and other nonpollinator selective forces acting during
      the seed-to-adult transition, countering selection imposed by pollinators.

PMID- 15729653
TI  - Optimal growth pattern of defensive organs: the diversity of shell growth among
      mollusks.
AB  - Mollusks show a diversity of shell growth patterns. We develop a model for the
      dynamic resource allocation to defense organs and analyze it with the Pontryagin
      maximum principle. A typical optimal growth schedule is composed of the initial
      phase of soft-body growth without shell followed by a simultaneous growth of
      shell and soft body and finally the reproductive phase without growth
      (simultaneous shell growth). If the defensible predation risk is low or if the
      cost of defense is high, the optimal strategy is to have no shell (shell-less
      growth). If defensible predation pressure or general mortality differs before and
      after maturation, an additional three strategies, characteristic of the exclusive
      growth of shell or soft body, can be optimal (sequential shell growth, additional
      body-expansion growth, and additional callus-building growth). These optimal
      strategies are in accord with the patterns observed for mollusks. In particular,
      the growth strategies with exclusive growth phase of external shells are
      preferred when durophagous predation pressure after maturation is higher than
      that before maturation. This result explains the observation that many tropical
      gastropods with thickened shell lips spend their vulnerable juvenile phase in
      sheltered habitats.

PMID- 15729654
TI  - Theory for designing nature reserves for single species.
AB  - We examine the question of the optimal number of reserves that should be
      established to maximize the persistence of a species. We assume that the mean
      time to extinction of a single population increases as a power of the habitat
      area, that there is a certain amount of habitat to be reserved, and that the aim
      is to determine how this habitat is most efficiently divided. The optimal
      configuration depends on whether the management objective is to maximize the mean
      time to extinction or minimize the risk of extinction. When maximizing the mean
      time to extinction, the optimal number of independent reserves does not depend on
      the amount of available habitat for the reserve system. In contrast, the risk of
      extinction is minimized when individual reserves are equal to the optimal patch
      size, making the optimal number of reserves linearly proportional to the amount
      of available habitat. A model that includes dispersal and correlation in the
      incidence of extinction demonstrates the importance of considering the relative
      rate at which these two factors decrease with distance between reserves. A small
      number of reserves is optimal when the mean time to extinction increases rapidly
      with habitat area or when risks of extinction are high.

PMID- 15729655
TI  - Temperature-related genetic changes in laboratory populations of Drosophila
      subobscura: evidence against simple climatic-based explanations for latitudinal
      clines.
AB  - Parallel latitudinal clines to the long-standing ones in the original Palearctic
      populations have independently evolved at different rates for chromosomal
      polymorphism and body size in South and North American populations of Drosophila
      subobscura since colonization around 25 years ago. This strongly suggests that
      (micro) evolutionary changes are largely predictable, but the underlying
      mechanisms are unknown. The putative role of temperature per se was investigated
      by using three sets of populations at each of three temperatures (13 degrees , 18
      degrees , and 22 degrees C) spanning much of the tolerable range for this
      species. We found a lower chromosomal diversity at the warmest temperature; a
      quick and consistent shift in gene arrangement frequencies in response to
      temperature; an evolutionary decrease in wing size, mediated by both cell area
      and cell number, at 18 degrees C; no relationship between wing size and those
      inversions involved in latitudinal clines; and a shortening of the basal length
      of longitudinal vein IV relative to its total length with increasing standard
      dose. The trends for chromosomal polymorphism and body size were generally
      inconsistent from simple climatic-based explanations of worldwide latitudinal
      patterns. The findings are discussed in the light of available information on D.
      subobscura and results from earlier thermal selection experiments with various
      Drosophila species.

PMID- 15729656
TI  - Invertebrate eggs can fly: evidence of waterfowl-mediated gene flow in aquatic
      invertebrates.
AB  - Waterfowl often have been assumed to disperse freshwater aquatic organisms
      between isolated wetlands, but no one has analyzed the impact of this transport
      on the population structure of aquatic organisms. For three cladocerans (Daphnia
      ambigua, Daphnia laevis, and Sida crystallina) and one bryozoan (Cristatella
      mucedo), we estimated the genetic distances between populations across North
      America using sequences of several mitochondrial DNA genes and genotypic
      frequencies at allozyme and microsatellite loci. Waterfowl movements across North
      America (estimated from band recovery data) explained a significant proportion of
      the gene flow occurring between populations across the continent for three of the
      four species, even after controlling for geographic distances between localities.
      The fourth species, S. crystallina, has propagules less likely to survive
      desiccation or ingestion by birds. Differences in the capacity to exploit bird
      mediated transport are likely to have important consequences for the ecology of
      aquatic communities and the spread of invasive species.

PMID- 15729657
TI  - Contrasting mutual sexual selection on homologous signal traits in Drosophila
      serrata.
AB  - The nature of male mating preferences, and how they differ from female mating
      preferences in species with conventional sex roles, has received little attention
      in sexual selection studies. We estimated the form and strength of sexual
      selection as a consequence of male and female mating preferences in a laboratory
      based population of Drosophila serrata. The differences between sexual selection
      on male and female signal traits (cuticular hydrocarbons [CHCs]) were evaluated
      within a formal framework of linear and nonlinear selection gradients. Females
      tended to exert linear sexual selection on male CHCs, whereas males preferred
      intermediate female CHC phenotypes leading to convex (stabilizing) selection
      gradients. Possible mechanisms determining the nonlinear nature of sexual
      selection on female CHCs are proposed.

PMID- 15729658
TI  - How far do animals go? Determinants of day range in mammals.
AB  - Day range (daily distance traveled) is an important measure for understanding
      relationships between animal distributions and food resources. However, our
      understanding of variation in day range across species is limited. Here we
      present a day range model and compare predictions against a comprehensive
      analysis of mammalian day range. As found in previous studies, day range scales
      near the 1/4 power of body mass. Also, consistent with model predictions,
      taxonomic groups differ in the way day range scales with mass, associated with
      the most common diet types and foraging habitats. Faunivores have the longest day
      ranges and steepest body mass scaling. Frugivores and herbivores show
      intermediate and low scaling exponents, respectively. Day range in primates did
      not scale with mass, which may be consistent with the prediction that three
      dimensional foraging habitats lead to lower exponents. Day ranges increase with
      group size in carnivores but not in other taxonomic groups.

PMID- 15729659
TI  - Explosive radiation of Malpighiales supports a mid-cretaceous origin of modern
      tropical rain forests.
AB  - Fossil data have been interpreted as indicating that Late Cretaceous tropical
      forests were open and dry adapted and that modern closed-canopy rain forest did
      not originate until after the Cretaceous-Tertiary (K/T) boundary. However, some
      mid-Cretaceous leaf floras have been interpreted as rain forest. Molecular
      divergence-time estimates within the clade Malpighiales, which constitute a large
      percentage of species in the shaded, shrub, and small tree layer in tropical rain
      forests worldwide, provide new tests of these hypotheses. We estimate that all 28
      major lineages (i.e., traditionally recognized families) within this clade
      originated in tropical rain forest well before the Tertiary, mostly during the
      Albian and Cenomanian (112-94 Ma). Their rapid rise in the mid-Cretaceous may
      have resulted from the origin of adaptations to survive and reproduce under a
      closed forest canopy. This pattern may also be paralleled by other similarly
      diverse lineages and supports fossil indications that closed-canopy tropical rain
      forests existed well before the K/T boundary. This case illustrates that dated
      phylogenies can provide an important new source of evidence bearing on the timing
      of major environmental changes, which may be especially useful when fossil
      evidence is limited or controversial.

PMID- 15729660
TI  - Scale-dependent feedback and regular spatial patterns in young mussel beds.
AB  - In the past decade, theoretical ecologists have emphasized that local
      interactions between predators and prey may invoke emergent spatial patterning at
      larger spatial scales. However, empirical evidence for the occurrence of emergent
      spatial patterning is scarce, which questions the relevance of the proposed
      mechanisms to ecological theory. We report on regular spatial patterns in young
      mussel beds on soft sediments in the Wadden Sea. We propose that scale-dependent
      feedback, resulting from short-range facilitation by mutual protection from waves
      and currents and long-range competition for algae, induces spatial self
      organization, thereby providing a possible explanation for the observed
      patterning. The emergent self-organization affects the functioning of mussel bed
      ecosystems by enhancing productivity and resilience against disturbance.
      Moreover, self-organization allows mussels to persist at algal concentrations
      that would not permit survival of mussels in a homogeneous bed. Our results
      emphasize the importance of self-organization in affecting the emergent
      properties of natural systems at larger spatial scales.

PMID- 15729661
TI  - Fitness correlates of song repertoire size in free-living song sparrows
      (Melospiza melodia).
AB  - Models of sexual selection propose that exaggerated secondary sexual ornaments
      indicate a male's own fitness and the fitness of his offspring. These hypotheses
      have rarely been thoroughly tested in free-living individuals because overall
      fitness, as opposed to fitness components, is difficult to measure. We used 20
      years of data from song sparrows (Melospiza melodia) inhabiting Mandarte Island,
      British Columbia, Canada, to test whether a male's song repertoire size, a
      secondary sexual trait, predicted overall measures of male or offspring fitness.
      Males with larger song repertoires contributed more independent and recruited
      offspring, and independent and recruited grandoffspring, to Mandarte's
      population. This was because these males lived longer and reared a greater
      proportion of hatched chicks to independence from parental care, not because
      females mated to males with larger repertoires laid or hatched more eggs.
      Furthermore, independent offspring of males with larger repertoires were more
      likely to recruit and then to leave more grandoffspring than were offspring of
      males with small repertoires. Although we cannot distinguish whether observed
      fitness variation reflected genetic or environmental effects on males or their
      offspring, these data suggest that female song sparrows would gain immediate and
      intergenerational fitness benefits by pairing with males with large song
      repertoires.

PMID- 15729662
TI  - The evolution of intergenerational discounting in offspring quality.
AB  - Intergenerational effects occur when an individual's actions affect not only its
      own survivorship and reproduction but also those of its offspring and possibly
      later descendants. In the presence of intergenerational effects, short-term and
      long-term measures of success (such as the expected numbers of surviving
      offspring and of farther descendants, respectively) may be in conflict. When such
      conflicts occur, life-history theory normally takes long-term measures to predict
      the outcome of selection. This ignores the fact that, because traits change in
      time--through mutation, sex, and recombination--long-term relations disintegrate.
      We study this issue with numerical simulations and analytical models combining
      intergenerational effects and evolutionary change. In the models, the parental
      investment per offspring, as well as the total reproductive effort, stand for
      investments in future generations. The models show that the rate of evolutionary
      change determines the level of those investments. Higher rates of mutation and of
      sexual as opposed to parthenogenetic reproduction favor lower parental investment
      per offspring and lower total reproductive effort. It follows that the level of
      investment of ancestors in descendants responds to the genetic relatedness
      between the generations of the lineage, in a manner unaccounted for by
      preexisting theory.

PMID- 15729663
TI  - Transient dynamics limit the effectiveness of keystone predation in bringing
      about coexistence.
AB  - We analyze the transient dynamics of simple models of keystone predation, in
      which a predator preferentially consumes the dominant of two (or more) competing
      prey species. We show that coexistence is unlikely in many systems characterized
      both by successful invasion of either prey species into the food web that lacks
      it and by a stable equilibrium with high densities of all species. Invasion of
      the predator-resistant consumer species often causes the resident, more
      vulnerable prey to crash to such low densities that extinction would occur for
      many realistic population sizes. Subsequent transient cycles may entail very low
      densities of the predator or of the initially successful invader, which may also
      preclude coexistence of finite populations. Factors causing particularly low
      minimum densities during the transient cycles include biotic limiting resources
      for the prey, limited resource partitioning between the prey, a highly efficient
      predator with relatively slow dynamics, and a vulnerable prey whose population
      dynamics are rapid relative to the less vulnerable prey. Under these conditions,
      coexistence of competing prey via keystone predation often requires that the
      prey's competitive or antipredator characteristics fall within very narrow
      ranges. Similar transient crashes are likely to occur in other food webs and food
      web models.

PMID- 15729664
TI  - Seed dispersal in heterogeneous environments: bridging the gap between
      mechanistic dispersal and forest dynamics models.
AB  - Seed dispersal is an important determinant of vegetation composition. We present
      a mechanistic model of seed dispersal by wind that incorporates heterogeneous
      vegetation structure. Vegetation affects wind speeds, a primary determinant of
      dispersal distance. Existing models combine wind speed and fall velocity of
      seeds. We expand on them by allowing vegetation, and thus wind profiles, to vary
      along seed trajectories, making the model applicable to any wind-dispersed plant
      in any community. Using seed trap data on seeds dispersing from forests into
      adjacent sites of two distinct vegetation structures, we show that our model was
      unbiased and accurate, even though dispersal patterns differed greatly between
      the two structures. Our spatially heterogeneous model performed better than
      models that assumed homogeneous vegetation for the same system. Its sensitivity
      to vegetation structure and ability to predict seed arrival when vegetation
      structure was incorporated demonstrates the model's utility for providing
      realistic estimates of seed arrival in realistic landscapes. Thus, we begin to
      bridge mechanistic seed dispersal and forest dynamics models. We discuss the
      merits of our model for incorporation into forest simulators, applications where
      such incorporation has been or is likely to be especially fruitful, and future
      model refinements to increase understanding of seed dispersal by wind.

PMID- 15729665
TI  - Predator diet breadth influences the relative importance of bottom-up and top
      down control of prey biomass and diversity.
AB  - We investigated the effects of predator diet breadth on the relative importance
      of bottom-up and top-down control of prey assemblages, using microbial food webs
      containing bacteria, bacterivorous protists and rotifers, and two different top
      predators. The experiment used a factorial design that independently manipulated
      productivity and the presence or absence of two top predators with different diet
      breadths. Predators included a "specialist" predatory ciliate Euplotes
      aediculatus, which was restricted to feeding on small prey, and a "generalist"
      predatory ciliate Stentor coeruleus, which could feed on the entire range of prey
      sizes. Both total prey biomass and prey diversity increased with productivity in
      the predator-free control and specialist predator treatments, a pattern
      consistent with bottom-up control, but both remained unchanged by productivity in
      the generalist predator treatment, a pattern consistent with top-down control.
      Linear food chain models adequately described responses in the generalist
      predator treatment, whereas food web models incorporating edible and inedible
      prey (which can coexist in the absence of predators) adequately described
      responses in the specialist predator treatment. These results suggest that
      predator diet breadth can play an important role in modulating the relative
      strength of bottom-up and top-down forces in ecological communities.

PMID- 15729666
TI  - Optimal replication of poliovirus within cells.
AB  - We construct a mathematical model of the within-cell replication of poliovirus, a
      prototypic RNA virus, and use realistic parameter estimates to describe the
      increase of copy number of the viral genome. Our initial model is essentially an
      exponential growth model; we also consider modifications of this model to account
      for resource utilization. The saturation of viral replication dynamics observed
      in experimental systems can be explained in terms of heavy resource use by the
      virus. We then use our models to consider the conditions under which the growth
      of poliovirus is optimized. Intriguingly, if poliovirus has optimized its
      replication within cells, the predicted ratio of positive to negative strands is
      close to what is actually observed. We interpret our findings in terms of the
      evolution of life-history traits.

PMID- 15729667
TI  - Metapopulation persistence in heterogeneous landscapes: lessons about the effect
      of stochasticity.
AB  - This article addresses an important aspect of the analysis of metapopulation
      persistence. It highlights some consequences of ignoring and including
      stochasticity in the sequence of extinction and colonization events. The results
      are based on a comparative analysis of the outcomes of two (one deterministic,
      one stochastic) spatially realistic metapopulation models and a search for common
      effects and differences. One key result of the article is that, under certain
      conditions, there are extra effects of the landscape structure (number and
      configuration of patches, patch size distribution) on metapopulation persistence
      if stochasticity is included. In these cases, ignoring or including stochasticity
      can change conclusions about the persistence status but also ranking orders,
      relative results, and qualitative trends. A list of conditions is provided under
      which including stochasticity is vital to prevent counterproductive conclusions
      about metapopulation persistence. The results of the overall study are condensed
      in five lessons about the effect of stochasticity. A number of implications for
      ecological theory and conservation management are discussed. The study
      demonstrates the potential of three recently published approximation formulas
      (metapopulation capacity lambdaM, mean lifetime Tm, and effective number of
      patches N) to serve as tools for ecological analysis and thinking.

PMID- 15729668
TI  - Matters of scale: positive allometry and the evolution of male dimorphisms.
AB  - The developmental independence of alternative phenotypes is key to evolutionary
      theories of phenotypic plasticity and the origins of diversity. Male dimorphisms
      associated with alternative reproductive tactics are widely cited examples of
      such facultative expression of divergent fitness optima. Current models for the
      evolution of male dimorphisms invoke a size-dependent threshold at which the
      phenotype is reprogrammed. We use predictions derived from allometric modeling to
      test for the existence of reprogramming thresholds in two species of beetle,
      Onthophagus taurus and Onthophagus binodis, and the European earwig Forficula
      auricularia. We also compare the allometry of a number of morphological traits to
      determine whether minor males suppress their secondary sexual traits. The
      intercept of the horn allometry was suppressed, but there was no evidence of
      reprogramming of horn growth in either beetle species. There was reprogramming in
      the earwig. In the beetles, the horn length in all males can be explained largely
      in terms of exponential horn growth following an extraordinarily steep power
      function. The asymptote in O. taurus can be explained by exponential growth
      meeting the constraint of resource exhaustion. These findings question the
      currently held view that beetle horn dimorphisms showcase the importance of
      developmental independence in the evolution of diversity.

PMID- 15729669
TI  - Mate-choice copying as Bayesian decision making.
AB  - Mate-choice copying by females has been reported in fishes (e.g., guppies) and
      lekking birds. Presumably, females assess males' quality using both information
      from direct observation of males and information acquired by observing other
      females' choices. Here, we study mathematically the conditions under which mate
      choice copying is advantageous on the basis of Bayesian decision theory. A female
      may observe the mate choice of another female, called the model female, who has
      performed an optimal choice based on her own judgment. The conditions required
      for the focal female to choose the same mate as that chosen by the model female
      should depend on the male's appearance to her, the reliability of her own
      judgment of male quality, and the reliability of the model females. When three or
      more females are involved, the optimal mate choice critically depends on whether
      multiple model females make decisions independently or they themselves copy the
      choices of others. If two equally reliable females choose different males, the
      choice of the second female, made knowing the choice of the first, should have a
      stronger effect on the choice of the third (focal) female. This "last-choice
      precedence" should be tested experimentally.

PMID- 15729671
TI  - Reinnervation of the rat levator ani muscle after neonatal denervation.
AB  - After axonal injury on postnatal day 14 (P14), but not P21, motoneurons in the
      spinal nucleus of the bulbocavernosus (SNB) do not display their normal response
      to circulating testosterone levels. This could result from a permanent disruption
      of communication between motoneurons and their testosterone-sensitive target
      muscles. We assessed the extent of reinnervation of one of these target muscles,
      the levator ani (LA) muscle, 5 months after the pudendal nerve was cut either on
      P14 or P21. The number of motoneurons innervating the LA in control and nerve cut
      animals was determined using retrograde labeling procedures. Functional recovery
      of the LA muscle was determined via the testing of its in situ contractile
      properties. Compared to control muscles, reinnervated LA muscles were smaller,
      had fewer muscle fibers, generated a lower maximum tetanic tension, and were more
      fatigable. In spite of the fact that fewer motoneurons reinnervated the LA muscle
      after nerve cut on P14 than on P21, there were no differences in the weight or
      contractile properties of the LA muscle between these two groups. These data
      suggest that motoneurons that survived injury on P14 innervated more muscle
      fibers than normal and exhibited a similar ability to functionally reinnervate
      the target muscle as those motoneurons that survived injury on P21.

PMID- 15729670
TI  - Effects of updating linkage evidence across subsets of data: reanalysis of the
      autism genetic resource exchange data set.
AB  - Results of autism linkage studies have been difficult to interpret across
      research groups, prompting the use of ever-increasing sample sizes to increase
      power. However, increasing sample size by pooling disparate collections for a
      single analysis may, in fact, not increase power in the face of genetic
      heterogeneity. Here, we applied the posterior probability of linkage (PPL), a
      method designed specifically to analyze multiple heterogeneous data sets, to the
      Autism Genetic Resource Exchange collection of families by analyzing six
      clinically defined subsets of the data and updating the PPL sequentially over the
      subsets. Our results indicate a substantial probability of linkage to chromosome
      1, which had been previously overlooked; our findings also provide a further
      characterization of the possible parent-of-origin effects at the 17q11 locus that
      were previously described in this sample. This analysis illustrates that the way
      in which heterogeneity is addressed in linkage analysis can dramatically affect
      the overall conclusions of a linkage study.

PMID- 15729673
TI  - Aspects of glycosidic bond formation in aqueous solution: chemical bonding and
      the role of water.
AB  - A model of the specific acid-catalyzed glycosidic bond formation in liquid water
      at ambient conditions is studied based on constrained Car-Parrinello ab initio
      molecular dynamics. Specifically the reaction of alpha-D-glucopyranose and
      methanol is found to proceed by a D(N)A(N) mechanism. The D(N) step consists of a
      concerted protonation of the O(1) hydroxyl leaving group; this process results in
      the breaking of the C(1)-O(1) bond, and oxocarbenium ion formation involving
      C(1)=O(5). The second step, A(N), is the formation of the C(1)-O(m) glycosidic
      bond, deprotonation of the methanol hydroxyl group O(m)H(m), and re-formation of
      the C(1)-O(5) single bond. A focus of this study is the analysis of the
      electronic structure during this condensed phase reaction relying on both
      Boys/Wannier localized orbitals and the electron localization function ELF. This
      analysis allows the clear elucidation of the chemical bonding features of the
      intermediate bracketed by the D(N) and A(N) steps, which is a non-solvent
      equilibrated oxocarbenium cation. Most interestingly, it is found that the oxygen
      in the pyranose ring becomes "desolvated" upon double bond/oxocarbenium
      formation, whereas it is engaged in the hydrogen-bonded water network before and
      after this period. This demonstrates that hydrogen bonding and thus the aqueous
      solvent play an active role in this reaction implying that microsolvation studies
      in the gas phase, both theoretical and experimental, might lead to qualitatively
      different reaction mechanisms compared to solution.

PMID- 15729672
TI  - Cactus stems (Opuntia spp.): a review on their chemistry, technology, and uses.
AB  - Although traditionally used as a valuable health supporting nutrient, the
      vegetative parts of Opuntia spp. plants are scarcely used in modern nutrition and
      medicine. While all kinds of different Opuntia spp. have been studied, a
      systematic approach regarding the inter-relationships between the composition and
      the pre- and postharvest conditions is still missing. Therefore, the present
      review compiles and discusses literature on the chemical composition of cactus
      stems, the knowledge on uses in food, medicine, and cosmetics. It is concluded
      that much research is needed to get an insight into the multitude of
      bioactivities reported in the traditional literature but also to take advantage
      of the respective constituents for food and pharmaceutical applications.

PMID- 15729674
TI  - Assembly of a series of malarial glycosylphosphatidylinositol anchor
      oligosaccharides.
AB  - We report an efficient and convergent synthesis of a series of oligosaccharides
      comprised of the malaria GPI glycan (2a), a promising anti-malaria vaccine
      candidate currently in preclinical trials and several related oligosaccharide
      sequences (3-8) that are possible biosynthetic precursors of the malarial GPI. A
      flexible synthetic strategy is disclosed that relies on a late-stage coupling
      between oligomannosides of varying length and pseudo-disaccharide glycosyl
      acceptor 11 to readily access various malarial GPI structures. Phosphorylation
      was accomplished by mild and efficient H-phosphonate chemistry before the final
      deprotection was carried out by using sodium in ammonia. The direct connection of
      a thiol group via a phosphate diester linkage to the inositol moiety provides a
      handle for easy conjugation of the GPI glycan to carrier proteins, immobilization
      on carbohydrate microarrays and photo-affinity labels identification. These
      synthetic oligosaccharides will serve as molecular probes.

PMID- 15729675
TI  - An Os(II)--bisbipyridine--4-picolinic acid complex mediates the biocatalytic
      growth of au nanoparticles: optical detection of glucose and acetylcholine
      esterase inhibition.
AB  - The complex Os(II)-bisbipyridine-4-picolinic acid, [Os(bpy)(2)PyCO(2)H](2+) (1),
      mediates the biocatalyzed growth of Au nanoparticles, Au NPs, and enables the
      spectroscopic assay of biocatalyzed transformations and enzyme inhibition by
      following the Au NP plasmon absorbance. In one system, [Os(bpy)(2)PyCO(2)H](2+)
      mediates the biocatalyzed oxidation of glucose and the growth of Au NPs in the
      presence of glucose oxidase, GOx, AuCl(4) (-), citrate and Au NP seeds. The
      mechanism of the Au NPs growth involves the oxidation of the
      [Os(bpy)(2)PyCO(2)H](2+) complex by AuCl(4) (-) to form [Os(bpy)(2)PyCO(2)H](3+)
      and Au(I). The [Os(bpy)(2)PyCO(2)H](3+) complex mediates the GOx biocatalyzed
      oxidation of glucose and the regeneration of the mediator 1. Citrate reduces
      Au(I) and enlarges the Au seeds by the catalytic deposition of gold on the Au NP
      seeds. In the second system, the enzyme acetylcholine esterase, AChE, is assayed
      by the catalytic growth of the Au NPs. The hydrolysis of acetylcholine (2) by
      AChE to choline is followed by the [Os(bpy)(2)PyCO(2)H](3+) mediated oxidation of
      choline to betaine and the concomitant growth of the Au NPs. The mediated growth
      of the Au NPs is inhibited by 1,5-bis(4-allyldimethylammonium-phenyl)pentane-3
      one dibromide (3). A competitive inhibition process was demonstrated (K(M)=0.13
      mM, K(I)=2.6 microM) by following the growth of the Au NPs.

PMID- 15729676
TI  - Synthesis of functionalized rab GTPases by a combination of solution- or solid
      phase lipopeptide synthesis with expressed protein ligation.
AB  - Prenylated proteins with non-native functionalities are generally very difficult
      to obtain by recombinant or enzymatic means. The semisynthesis of preparative
      amounts of prenylated Rab guanosine triphosphatases (GTPases) from recombinant
      proteins and synthetic prenylated peptides depends largely on the availability of
      functionalised prenylated peptides corresponding to the proteins' native
      structure or modifications thereof. Here, we describe and compare solution-phase
      and solid-phase strategies for the generation of peptides corresponding to the
      prenylated C terminus of Rab7 GTPase. The solid-phase with utilisation of a
      hydrazide linker emerges as the more favourable approach. It allows a fast and
      practical synthesis of pure peptides and gives a high degree of flexibility in
      their modification. To facilitate the analysis of semisynthetic proteins, the
      synthesised peptides were equipped with a fluorescent group. Using the described
      approach, we introduced fluorophores at several different positions of the Rab7 C
      terminus. The position of the incorporated fluorescent groups in the peptides did
      not influence the protein-ligation reaction, as the generated peptides could be
      ligated onto thioester-tagged Rab7. However, it was found that the positioning of
      the fluorescent group had an influence on the functionality of the Rab7 proteins;
      analysis of the interaction of the semisynthetic Rab7 proteins with REP (Rab
      escort protein) and GDI (guanosine diphosphate dissociation inhibitor) molecules
      revealed that modification of the peptide side chains or of the C-terminal
      isoprenoid did not significantly interfere with complex formation. However,
      functionalisation of the C terminus was found to have an adverse effect on
      complex formation and stability, possibly reflecting low structural flexibility
      of the Rab GDI/REP molecules in the vicinity of the lipid-binding site.

PMID- 15729677
TI  - Total synthesis of mauritines A, B, C, and F: cyclopeptide alkaloids with a 14
      membered paracyclophane unit.
AB  - A unified strategy for the synthesis of mauritines A (5), B (6), C (7), and F
      (10) has been developed based on a key intramolecular nucleophilic aromatic
      substitution reaction (S(N)Ar) for the formation of the strained 14-membered
      paracyclophane. It was demonstrated that the outcome of the cycloetherification
      is independent of the stereochemistry of the peptide backbone and that both (1R)
      16 and (1S)-16 cyclized smoothly to provide the corresponding macrocycle. On the
      other hand, dehydration of the secondary benzylic alcohol, via the phenylselenide
      intermediate, is configuration dependent. (1R)-25 underwent the two-step syn
      elimination much more easily than (1S)-22. A modified reductive deamination
      procedure via the diazonium intermediate was developed. A complete assignment of
      proton and carbon NMR spectroscopy signals for these natural products is reported
      for the first time.

PMID- 15729678
TI  - Water-insoluble Ag-U-organic assemblies with photocatalytic activity.
AB  - Two metal-organic coordination polymers [Ag(bipy)(UO(2))(bdc)(1.5)] (bipy=2,2'
      bipyridyl, bdc=1,4-benzenedicarboxylate) and [Ag(2)(phen)(2)UO(2)(btec)]
      (phen=1,10-phenanthroline, btec=1,2,4,5-benzenetetracarboxylate) were obtained by
      hydrothermal assembly of the d(10) metal silver and the 5f metal uranium with
      mixed ligands. Both compounds form two-dimensional networks with pi-pi overlap
      interactions between the aromatic fragments in the neighboring layers. In aqueous
      suspension the two water-insoluble materials show photocatalytic degradation
      performance superior to that of commercial TiO(2) (Degussa P-25) when tested on
      nonbiodegradable rhodamine B (RhB) as model pollutant. The relationship between
      the structure of the photocatalysts and the photocatalytic activity was also
      elucidated. On the basis of the monitored intermediate species and the final
      mineralized products, it is proposed that the possible reaction mechanism for the
      photodegradation (oxidation) of RhB in aqueous solution catalyzed by the two
      assembly compounds involves photoexcitation of uranyl centers and molecular
      oxygen.

PMID- 15729679
TI  - Regioselective intramolecular Pauson-Khand reactions of C60: an electrochemical
      study and theoretical underpinning.
AB  - Suitably functionalized fulleropyrrolidines endowed with one or two propargyl
      groups at the C-2 position of the pyrrolidine ring (1,6-enynes) react efficiently
      and regioselectively with [Co2(CO)8] to afford the respective Pauson-Khand
      products with an unprecedented three (5 a-d, 7, and 24) or five (25) pentagonal
      rings, respectively, fused onto the fullerene sphere. Fulleropyrrolidines with
      1,7-, 1,9-, 1,10-, or 1,11-enyne moieties do not undergo the PK reaction and,
      instead, the intermediate dicobalt complexes formed with the alkynyl group are
      isolated in quantitative yields. These differences in reactivity have been
      studied by DFT calculations with a generalized gradient approximation (GGA)
      functional and several important energy and structural differences were found for
      the intermediates formed by the interaction between the coordinatively
      unsaturated Co atom and the pi system of C60 in 1,6- and 1,7-enynes. The
      different lengths of the alkyne chains are responsible for the observed
      reactivities. Cyclic voltammetry reveals that the presence of the
      cyclopentenone's carbonyl group connected directly to the C60 core results in PK
      compounds with remarkable electron-accepting ability.

PMID- 15729680
TI  - Allylic stereocontrol of the intramolecular Diels-Alder reaction.
AB  - The stereochemical outcome of the intramolecular Diels-Alder reaction of ester
      linked 1,3,8-nonatrienes can be controlled by substituents about a stereogenic
      center attached to C1. The scope and limitations of this approach have been
      investigated, with variation in substrate structure about the allylic
      stereocenter and the dienophile. The stereochemical outcomes of these reactions
      are explained by reference to B3 LYP/6-31G(d) transition structures. New insights
      into the conformational preferences of allylic alcohol derivatives are reported,
      results which allow an explanation of the differing levels of pi-diastereofacial
      selectivity and cis/trans (i.e. endo/exo) selectivity from the reaction.

PMID- 15729681
TI  - Generation of quaternary stereocenters by asymmetric Michael reactions: enamine
      regiochemistry as configuration switch.
AB  - Regioselective enamine formation from cyclic beta-diketones 1 is obtained by the
      appropriate choice of activating agent: Bronsted acid catalyzed condensation
      gives endocyclic enamines 3 as the thermodynamically favored products. Activation
      with Lewis acid BF(3).OEt(2) affords betaines 8 as intermediate products, which
      can be reacted with L-valine diethylamide (2) to preferentially furnish exocyclic
      enamines 4 as kinetic products. Derivatives with quaternary stereocenters were
      accessible from both isomeric enamines by using asymmetric, copper(II)-catalyzed
      Michael reactions at ambient temperature. Both regioisomers afford the triketones
      7 with the same constitution but bearing the opposite absolute configuration at
      the quaternary stereocenter. Thus, both enantiomers of the product are prepared
      by using the same chiral auxiliary derived from L-valine.

PMID- 15729682
TI  - Mixed-valence, mixed-spin-state, and heterometallic [2x2] grid-type arrays based
      on heteroditopic hydrazone ligands: synthesis and electrochemical features.
AB  - An extended family of heterometallic [(M1)2(M2)2(L-)4](n+) [2x2] grid-type arrays
      1-9 has been prepared. The three-tiered synthetic route encompasses
      regioselective, redox and enantioselective features and is based on the stepwise
      construction of heteroditopic hydrazone ligands A-C. These ligands contain
      ionisable NH and nonionisable NMe hydrazone units, which allows the metal redox
      properties to be controlled according to the charge on the ligand binding pocket.
      The 2-pyrimidine (R) and 6-pyridine (R') substituents have a significant effect
      on complex geometry and influence both the electrochemical and magnetic behaviour
      of the system. 1H NMR spectroscopic studies show that the Fe(II) ions in the grid
      can be low spin, high spin or spin crossover depending on the steric effect of
      substituents R and R'. This steric effect has been manipulated to construct an
      unusual array possessing two low-spin and two spin-crossover Fe(II) centres (grid
      8). Electrochemical studies were performed for the grid-type arrays 1-9 and their
      respective mononuclear precursor complexes 10-13. The grids function as electron
      reservoirs and display up to eight monoelectronic, reversible reduction steps.
      These processes generally occur in pairs and are assigned to ligand-based
      reductions and to the Co(III)/Co(II) redox couple. Individual metal ions in the
      heterometallic grid motif can be selectively addressed electrochemically (e.g.,
      either the Co(III) or Fe(II) ions can be targeted in grids 2 and 5). The Fe(II)
      oxidation potential is governed by the charge on the ligand binding unit, rather
      than the spin state, thus permitting facile electrochemical discrimination
      between the two types of Fe(II) centre in 7 or in 8. Such multistable
      heterometallic [2x2] gridlike arrays are of great interest for future
      supramolecular devices incorporating multilevel redox activity.

PMID- 15729683
TI  - Zirconium bis(indenyl) sandwich complexes with an unprecedented indenyl
      coordination mode and their role in the reactivity of the parent bent
      metallocenes: a detailed DFT mechanistic study.
AB  - The mechanisms of three closely related reactions were studied in detail by means
      of DFT/B3 LYP calculations with a VDZP basis set. Those reactions correspond to
      1) the reductive elimination of methane from [Zr(eta5-Ind)2(CH3)(H)] (Ind=C9H7-,
      indenyl), 2) the formation of the THF adduct, [Zr(eta5-Ind)(eta6-Ind)(thf)] and
      3) the interconversion between the two indenyl ligands in the Zr sandwich
      complex, [Zr(eta5-Ind)(eta9-Ind)], which forms the link between the two former
      reactions. An analysis of the electronic structure of this species indicates a
      saturated 18-electron complex. A full understanding of the indenyl interchange
      process required the characterisation of several isomers of the Zr-bis(indenyl)
      species, corresponding to different spin states (S=0 and S=1), different
      coordination modes of the two indenyl ligands (eta5/eta9, eta5/eta5 and
      eta6/eta9), and three conformations for each isomer (syn, anti, and gauche). The
      fluxionality observed was found to occur in a mechanism involving bis(eta5-Ind)
      intermediates, and the calculated activation energy (11-14 kcal mol(-1)) compares
      very well with the experimental values. Two alternative mechanisms were explored
      for the reductive elimination of methane from the methyl/hydride complex. In the
      more favourable one, the initial complex, [Zr(eta5-Ind)2(CH3)(H)], yields
      [Zr(eta5-Ind)2] and methane in one crucial step, followed by a smooth transition
      of the Zr intermediate to the more stable eta5/eta9-species. The overall
      activation energy calculated (Ea=29 kcal mol(-1)) compares well with experimental
      values for related species. The formation of the THF adduct follows a one step
      mechanism from the appropriate conformer of the [Zr(eta5-Ind)(eta9-Ind)] complex,
      producing easily (Ea=6.5 kcal mol(-1)) the known product, [Zr(eta5-Ind)(eta6
      Ind)(thf)], a species previously characterised by X-ray crystallography. This
      complex was found to be trapped in a potential well that prevents it from
      evolving to the 3.4 kcal mol(-1) more stable isomer, [Zr(eta5-Ind)2(thf)], with
      both indenyl ligands in a eta5-coordination mode and a spin-triplet state (S=1).

PMID- 15729684
TI  - Influence of the biogenic amine tyramine on ethanol-induced behaviors in
      Drosophila.
AB  - The biogenic amine tyramine has been implicated in drug-induced behavior. The
      Drosophila inactive mutant is characterized by reduced tyramine and octopamine
      levels and is defective in cocaine sensitization. To test whether there is an
      overlap in the use of the amine neurotransmitter system in ethanol- and cocaine
      induced behaviors, mutant analyses were extended to the phenotypic
      characterization of inactive and other mutants effecting the tyramine and
      octopamine neurotransmitter system. The inactive mutant displays increased
      ethanol sensitivity and is impaired in the initial startle response upon ethanol
      application. Furthermore, this mutant fails to regulate its alcohol-induced
      hyperactivity properly. In contrast to the defects seen after cocaine
      application, inactive mutants develop normal ethanol tolerance and sensitize to
      the locomotor activating effect of ethanol. The tyramine-beta-hydroxylase mutant
      (TbetaH) with increased tyramine and depleted octopamine levels displays normal
      ethanol sensitivity, a startle repression, and hyperactivates more in response to
      ethanol. In addition, TbetaH mutants fail to develop a tolerance to the
      hyperactivating effect of ethanol. Ethanol-induced sensitization does not seem to
      be impaired in either mutant, suggesting that tyramine is not required for this
      process. The comparative analysis of the phenotypes associated with inactive and
      TbetaH mutants suggests that the fine tuning of ethanol-induced hyperactivity can
      be correlated with different tyramine levels. Defects in other aspects of ethanol
      induced behaviors might be due to different molecules or mechanisms.

PMID- 15729685
TI  - Neurogenesis, migration, and apoptosis in the vomeronasal epithelium of adult
      mice.
AB  - The location of neurogenesis and the direction of migration of neurons in the
      adult mouse vomeronasal organ is controversial. Cell division occurs at the
      center, and particularly, at the edges of the epithelium. Newly generated cells
      at the center of the epithelium participate in neurogenesis, however, it is
      unknown to what extent dividing cells at the edges participate in growth, become
      apoptotic or mature into neurons. Premitotic cells were labeled with
      bromodeoxyuridine (BrdU) in adult mice and animals allowed to survive for
      different postinjection periods. The terminal deoxynucleotidyl transferase
      mediated biotinylated dUTP nick end-labeling (TUNEL) method was used to show the
      distribution of apoptotic cells. The vertical and horizontal position of BrdU
      labeled cells was analyzed as a function of postinjection survival time. Vertical
      and horizontal migration of BrdU-labeled cells were detected. Cells in the
      central portions of the epithelium migrated vertically to become neurons as
      demonstrated by co-expression of olfactory marker protein. Cells at the edges
      migrated horizontally very slowly (less than 10% of the distance from the edge to
      the center of the epithelium per month), thus indicating that these cells
      participate in cell renewal exclusively in marginal regions. Neural turnover in
      the mouse vomeronasal epithelium, therefore appears to occur through a process of
      vertical migration. Data on the distribution of apoptotic cells indicate that a
      number of dividing cells throughout the epithelium, but particularly at the
      edges, die before becoming functional neurons. Accordingly, most dividing cells
      at the edges probably constitute a reservoir of stem cells dying before
      differentiation.

PMID- 15729686
TI  - Synergistic activity of Sef and Sprouty proteins in regulating the expression of
      Gbx2 in the mid-hindbrain region.
AB  - Sef and Sprouty proteins function as feedback antagonists of fibroblast growth
      factor (Fgf) signaling in zebrafish embryos. To study the role of Sef in mice, we
      generated Sef homozygous mutant animals. These animals are viable and show normal
      expression of mid-hindbrain genes at embryonic days 8.5 and 9.5. To investigate
      the possibility of functional synergism between Sef and Sprouty proteins, we
      electroporated Sprouty2(Y55A), which functions in a dominant-negative manner in
      tissue culture cells into the mid-hindbrain region of wildtype and Sef mutant
      embryos. The expression pattern of Gbx2, a downstream target of Fgf signaling,
      was expanded or shifted in electroporated embryos, and this effect was
      significantly enhanced in the Sef mutant background. Altogether, our results
      demonstrate that Sef and Sproutys function synergistically to regulate Gbx2
      expression in the anterior hindbrain.

PMID- 15729687
TI  - Ligand-activated Flpe for temporally regulated gene modifications.
AB  - The selectivity by which site-specific recombinase-mediated genetic changes can
      be targeted to specific cells in the mouse has been limited by the fact that many
      genes used as recombinase "drivers" are expressed either in cell populations that
      change over time or constitutively in a given cell population for an extended
      time period, for example, in a germinal zone that gives rise successively to
      different lineages. These scenarios limit the selective dimension of conditional
      gene modification experiments as they preclude studying the later-generated
      lineages either because of earlier phenotypes (in the case of conditional
      mutagenesis experiments) or because the early and permanent activation of a
      reporter in a germinal zone results in all descendant lineages being marked (in
      the case of fate-mapping experiments). To circumvent this limitation, inducible
      forms of Cre recombinase have been developed, enabling the induction of genetic
      changes in late embryonic or adult cells accessible only through late aspects of
      a dynamic driver gene expression profile. To increase the number of tools
      available for engineering genetic changes in selective cell populations, we have
      generated a ligand-regulated form of Flpe using the recombinase-steroid receptor
      fusion approach. In two prototypical scenarios, we show that the fused gene
      product, FlpeER(T2), is competent to mediate DNA recombination in vivo and
      responds specifically to the inducer tamoxifen in a dose-dependent manner without
      detectable background activity.

PMID- 15729688
TI  - The partial retro-inverso modification: a road traveled together.
AB  - In the mid-1970s, Dr. Murray Goodman was interested in a reversed peptide bond as
      a surrogate to understand the functional role of the amide bond in aspartame, a
      dipeptide sweetener. Very soon, realizing the breath and potential of this
      modification, Murray expanded this activity into a full program and I was
      fortunate to be part of it. Together we formulated new concepts such as the
      partially modified retro-inverso and end-group modified retro-inverso
      transformations, tested hypotheses, generated novel nomenclature, developed
      synthetic routes, characterized the preferred conformations of the unique
      building blocks employed in this modification, the gem-diaminoalkyl and the C2
      substituted malonyl residues, and studied the biological activity of retro
      inverso isomers of bioactive peptides. In the early 1980s several laboratories
      initiated extensive research targeted at the retro-inverso modification. The
      revival of this field led to new applications, new methods of synthesis, and new
      insights on the conformational and topological properties of the retro-inverso
      modification. Among the fields that embraced the retro-inverso concept were
      immunology as pertains to subjects such as synthetic vaccines, immunomodulators,
      and diagnostic tools, and drug delivery field as pertains to targeted and
      nontargeted cell permeation vectors loaded with bioactive cargo. Doctor Murray
      Goodman's sudden death leaves behind not only family, friends, and colleagues,
      but also an impressive record of scientific achievements among which is the
      revival of the modern era of the retro-inverso transformation. Murray's numerous
      contributions, excellent leadership, enthusiastic promotion, and outstanding
      teachings in this field will carry and illuminate his memory far into the future.

PMID- 15729689
TI  - MyoD-cre transgenic mice: a model for conditional mutagenesis and lineage tracing
      of skeletal muscle.
AB  - The Cre-loxP recombination system has been used to great advantage in vivo for
      conditional gene targeting, lineage tracing, and other applications. To express
      cre in skeletal myoblasts and muscle fibers, we utilized the well-characterized
      transcriptional regulatory regions of the muscle determination gene, MyoD.
      Transgenic mouse lines were produced (F3/-2.5cre) in which the cre gene is driven
      by the MyoD promoter and core enhancer, which directs the early activation of
      MyoD. Specificity of cre expression and efficiency of recombination was
      determined by monitoring reporter gene expression after crossing to the Cre
      dependent reporter lines, R26R and Z/AP. Efficient labeling of embryonic and
      fetal myoblasts and muscle fibers was observed, with timing that was similar
      (branchial arches and limb buds) or slightly delayed (myotomes) relative to the
      endogenous MyoD gene. In satellite cell cultures, a strict concordance between
      MyoD protein and reporter gene expression was observed, demonstrating the muscle
      specificity and efficiency of Cre-mediated recombination. Nascent muscle fibers
      were labeled following injury of adult muscle, indicating recombination in
      satellite cells or their daughters in vivo.

PMID- 15729690
TI  - Nasopharyngeal carcinoma-susceptibility locus is localized to a 132 kb segment
      containing HLA-A using high-resolution microsatellite mapping.
AB  - Nasopharyngeal carcinoma (NPC) is an epithelial tumor uniquely prevalent in
      southern Chinese. HLA-A2 is associated with NPC. In a previous study, we showed
      that the genes associated with susceptibility to NPC are primarily located within
      the HLA-A locus in Taiwanese NPC patients. However, the pathogenic genes causing
      NPC susceptibility remain unknown. Here, 8 polymorphic microsatellite markers
      distributed over a 1 megabase region surrounding the HLA-A locus were subjected
      to genetic analysis for the NPC-susceptibility locus. Statistical studies of
      associated alleles detected on each microsatellite locus showed that the NPC-
      susceptibility genes are most likely located between the D6S510 and D6S211
      markers within a 132 kb segment containing the HLA-A locus. These results
      undoubtedly would facilitate the further positional cloning of the NPC
      susceptibility locus, which has been elusive for the past 30 years.

PMID- 15729691
TI  - Expression of cell cycle markers and human papillomavirus infection in oral
      squamous cell carcinoma: use of fuzzy neural networks.
AB  - Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship
      between some cell cycle markers and HPV infection, conditionally to age, gender
      and certain habits of patients, and to assess the ability of fuzzy neural
      networks (FNNs) in building up an adequate predictive model based on logic
      inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for
      MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in
      exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV
      genotype was determined by direct DNA sequencing. Data were analyzed by
      traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %)
      without any significant higher risk of HPV infection with respect to the
      sociodemographic variables considered (p > 0.2), apart from tobacco smoking,
      reported in 44.4% of OSCC HPV-positive vs. 100% HPV-negative subjects (p =
      0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was
      expressed significantly more in HPV-negative than in HPV-positive OSCC [root mean
      square error (RMSE) = 5.89 x 10(-6), % predicted 100.0]; furthermore, smoking
      played a protective role for survivin expression in HPV-positive cases (OR =
      0.019, 95%CI 0.001-0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a
      small sample size, allowed us to confirm data by TS and to hypothesize a
      different cell cycle pattern for HPV-positive vs. HPV-negative OSCC. In the
      latter cases, the relevance of apoptotic vs. proliferative markers suggested that
      they may be related to the different supposed outcome of HPV-negative OSCC and
      that HPV may have a protective role in the expression level of survivin,
      especially in tobacco smokers.

PMID- 15729692
TI  - Soluble branched (1,4)-beta-D-glucans from Acetobacter species enhance antitumor
      activities against MHC class I-negative and -positive malignant melanoma through
      augmented NK activity and cytotoxic T-cell response.
AB  - We previously found that an extracellular polysaccharide, AC-1, produced by
      Acetobacter polysaccharogenes composed of (1,4)-beta-D-glucan with branches of
      glucosyl residues showed a strong activity to induce production of interleukin
      (IL)-12 p40 and tumor necrosis factor-alpha by macrophage cell lines in vitro via
      Toll-like receptor-4 signaling. In the present study, we examined the effects of
      oral administration of AC-1 on protection against 2 types of murine B16 melanoma
      lines, major histocompatibility complex (MHC) class I-negative B16L and MHC class
      I gene-transfected B16K(b) cells. Mice were inoculated subcutaneously with B16L
      or B16K(b) cells on day 0 and administrated intragastrically with AC-1 or PBS
      once every 5 days from 1 day before tumor inoculation. The tumor growth was
      severely retarded in AC-1-treated mice after subcutaneous inoculation with B16L
      or B16K(b) cells. The AC-1-treated mice showed augmented natural killer (NK) cell
      activity against B16L cells, and in vivo depletion of NK cells by antiasialoGM1
      antibody (Ab) treatment abrogated the antitumor activity in AC-1-treated mice. On
      the other hand, AC-1-treated mice inoculated with B16K(b) cells developed a
      significantly higher level of cytotoxic T-lymphocyte response against B16K(b)
      cells, and in vivo depletion of CD8(+) T cells by anti-CD8 mAb treatment
      abrogated the antitumor activity. Thus, AC-1 augmented antitumor activity against
      different tumors via augmentation of different antitumor mechanisms. These
      results suggest a possible prophylactic application of AC-1 for human neoplasms
      irrespective of expression levels of their MHC class I molecules.

PMID- 15729693
TI  - Ly6 family member C4.4A binds laminins 1 and 5, associates with galectin-3 and
      supports cell migration.
AB  - C4.4A is a member of the Ly6 family, with low homology to uPAR. It has been
      detected mainly on metastasizing carcinoma cells and proposed to be involved in
      wound healing. So far, C4.4A has been observed as an orphan receptor, and its
      functional activity has not been explored. Using recombinant rat C4.4A (rrC4.4A)
      made in a eukaryotic expression system, we demonstrate by immunohistology that
      C4.4A ligands are strongly expressed in tissues adjacent to squamous epithelia
      of, e.g., tongue and esophagus, the expression pattern partly overlapping with
      laminin (LN) and complementing the C4.4A expression that is found predominantly
      on the basal layers of squamous epithelium. ELISA screening of several components
      of the extracellular matrix revealed selective binding of rrC4.4A to LN1 and LN5
      and that transfection of the BSp73AS tumor line with C4.4A cDNA (BSp73AS-1B1)
      promoted LN1 and LN5 binding. Binding of BSp73AS-1B1 to LN5 and, less markedly,
      LN1 induced spreading, lamellipodia formation and migration. C4.4A also
      associates with galectin-3 in nontransformed tissues and tumor lines. There is
      evidence that the association of C4.4A with galectin-3 influences LN adhesion.
      C4.4A was described originally as a metastasis-associated molecule. Our findings
      that LN1 and LN5 are C4.4A ligands, that galectin-3 associates with C4.4A and
      that C4.4A ligand binding confers a migratory phenotype are well in line with the
      supposed metastasis association.

PMID- 15729694
TI  - Pilot screening programme for small molecule activators of p53.
AB  - Activation of the p53 tumour suppressor is predicted to have therapeutically
      beneficial effects. Many current anti-cancer therapies activate the p53 response
      via DNA damage. Non-genotoxic activation of the p53 pathway would open the way to
      long-term and possibly prophylactic treatments. We have established a simple
      protocol to screen small compound libraries for activators of p53-dependent
      transcription, and to select and characterise the most interesting hits, which
      include non-genotoxic activators. These compounds or their derivatives are of
      potential clinical interest. This approach may also lead to the identification of
      novel p53-activating compound families and possibly to the description of novel
      molecular pathways regulating p53 activity.

PMID- 15729695
TI  - Real-time RT-PCR detection of CK19, CK7 and MUC1 mRNA for diagnosis of lymph node
      micrometastases in non small cell lung carcinoma.
AB  - Metastatic lymph nodes (LNs) are the major prognostic factor in resected non
      small cell lung carcinoma (NSCLC). However, almost 50% of pN0 patients relapse,
      suggesting metastatic cells undetected by current staging procedures. A
      combination of markers [cytokeratins 19 and 7 (CK19, CK7) and mucin type 1 (MUC1)
      mRNAs] was therefore evaluated by real-time RT-PCR in order to detect occult
      cancer cells. Forty-three NSCLC tumor samples, 4 micrometastatic, 6 metastatic
      and 84 histologically negative mediastinal LNs from 19 patients with NSCLC were
      evaluated as well as blood mononuclear cells from 29 healthy volunteers and 17
      benign LNs. When tested on cell lines, RT-PCR was particularly efficient for
      evaluation of CK19, CK7 and MUC1 mRNA expression. All tumor samples were positive
      for at least 1 marker and 74% of samples were positive for all 3 markers. CK7 and
      CK19 mRNA were not detected in benign LN and blood cells from healthy donors in
      contrast with MUC1 mRNA. Only CK7 and CK19 mRNA were therefore used for
      evaluation of mediastinal LNs: the 6 histologically metastatic and the 4
      micrometastatic LNs were positive for at least one marker. Among the 84
      histologically negative LNs, 6 (7%) were positive for at least one marker,
      potentially changing the stage of 2 out of 19 patients. In conclusion, in our
      feasibility study, parallel molecular detection of CK19 and CK7 mRNA can be
      considered a specific diagnostic tool for the assessment of microscopic lymphatic
      spread. Its prognostic impact remains to be evaluated in a prospective study.

PMID- 15729696
TI  - Responses of human T cells to peptides flanking the tandem repeat and overlapping
      the signal sequence of MUC1.
AB  - The epithelial mucin MUC1 is one of the few tumour-associated antigens identified
      for breast cancer. Several MUC1-derived peptides binding HLA-A*0201 molecules
      have been identified that correspond to sequences outside the tandem repeat.
      Immunisation with some of these peptides induces protective antitumour immunity
      in mice. Another HLA-A*0201-binding peptide has been identified in a human
      system. We have evaluated the CD8(+) T-cell responses to all these peptides using
      peripheral blood lymphocytes from breast cancer patients and normal donors.
      Specific CD8(+) T-cell responses could be generated in vitro against some of
      these peptides but only after several rounds of in vitro restimulation, and they
      did not recognise human cells endogenously expressing the antigen. Nevertheless,
      T cells recognised by HLA-A*0201 tetramers carrying a peptide from the signal
      sequence (LLLLTVLTV) could be detected in the peripheral blood of some HLA
      A*0201(+) breast cancer patients but not in healthy adults. This peptide is the
      only one of those tested which was identified in the human system, and the
      results emphasize the potential problems involved in translation of data from
      laboratory animal models to the human system.

PMID- 15729697
TI  - Family history of cancer and risk of second malignancies in young cancer patients
      in Trieste, Italy.
AB  - We carried out a cohort study in the Italian province of Trieste (2001
      population, 242,000) to ascertain whether the risk of a subsequent primary cancer
      among 265 individuals diagnosed with a first malignancy at ages up to 25 years
      between 1971 and 1993 differed from that in the general population and to
      evaluate the effect of cancer family history, quantified by the family risk index
      (FRI), on the occurrence of second primaries. During the follow-up (median
      duration = 10 years; 25th-75th percentile = 2-16), 15 cohort members developed a
      second cancer vs. 1.60 expected for a standardized incidence ratio (SIR) of 9.4
      (p < 0.0001). The overall SIR fell to 4.7 (p = 0.004) after excluding the 8
      patients with well-known cancer-predisposing conditions (SIR = 300.0; p < 0.0001)
      and the 50 with a positive family history (FRI >/= 1.0) of malignant tumors (SIR
      = 20.0; p < 0.0001). Among 114 patients treated with radiotherapy and
      chemotherapy for their first neoplasms and not affected by predisposing
      disorders, 23 with a positive family history of cancer showed a 6.4-fold excess
      risk of second primaries (p = 0.008) compared with 91 with a negative history
      (FRI < 1.0). It is imperative that clinicians carefully and regularly evaluate
      cancer family history of young patients with malignancies. This would enable them
      to identify possible individual and familial features in patients at higher risk
      of multiple primaries and to adopt more suitable preventive and therapeutic
      measures.

PMID- 15729698
TI  - XPC polymorphisms and lung cancer risk.
AB  - Polymorphisms in DNA repair genes may be associated with differences in the
      capacity to repair DNA damage and thereby influence an individual's
      susceptibility to smoking-related cancer. To test this hypothesis, we
      investigated the potential association of 7 XPC polymorphisms (-449G-->C, -371G-
      >A, -27G-->C, Val499Arg, PAT-/+, IVS11-5C-->A and Lys939Gln) and their haplotypes
      with lung cancer risk in a Korean population. XPC genotypes were determined in
      432 lung cancer patients and 432 healthy controls frequency-matched for age and
      sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase
      program. The combined -27CG+CC genotype was associated with a significantly
      increased risk for overall lung cancer compared to the -27GG genotype (adjusted
      OR = 1.97, 95% CI 1.22-3.17, p = 0.005). The other 6 polymorphisms were not
      significantly associated with overall risk of lung cancer. When lung cancer cases
      were categorized by tumor histology, the -371AA genotype was associated with a
      significantly increased risk of squamous cell carcinoma compared to the combined 
      371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09-4.00, p = 0.03). The PAT
      /+, IVS11-5C-->A and Lys939Gln polymorphisms were associated with a significantly
      decreased risk of small cell carcinoma (SM) under a dominant model for the
      polymorphic allele (adjusted OR = 0.49, 95% CI 0.29-0.82, p = 0.006; adjusted OR
      = 0.60, 95% CI 0.36-1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35-0.97, p =
      0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222)
      containing the PAT+/IVS11-5A/939Gln alleles was associated with a significantly
      decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37-0.85, p = 0.007 and
      Bonferroni-corrected p = 0.049), whereas haplotype 5 (1122111) containing the 
      27C allele was associated with a significantly increased risk of SM (adjusted OR
      = 2.88, 95% CI 1.41-5.87, p = 0.004 and Bonferroni-corrected p = 0.028). These
      results suggest that XPC polymorphisms/haplotypes may contribute to genetic
      susceptibility for lung cancer.

PMID- 15729699
TI  - Enzymatic detection of precursor cell populations of preneoplastic foci positive
      for gamma-glutamyltranspeptidase in rat liver.
AB  - An improved staining method for gamma-glutamyltranspeptidase (GGT) was developed
      using Vibratome-prepared microslices. Microscopic precursor cell populations of
      preneoplastic foci positive for the marker enzyme were detectable sequentially in
      rat liver by tracing back from 5 to 1 week after carcinogen injection in a
      hepatocarcinogenesis model. Mirror-image comparisons of serial sections stained
      for GGT activity and immunocytochemically stained for GST-P (glutathione S
      transferase P-form) revealed that GGT expression was confined within GST-P(+)
      cell populations (GST-P(+) minifoci), which are induced in the periportal area
      (zone 1) of the liver. GGT expression level differed from one minifocus to
      another, and the larger the GST-P(+) focus, the stronger was the GGT expression
      in it, indicating that GST-P(+)/GGT(-) phenotypes are convertible into
      proliferating GST-P(+)/GGT(+) ones. Our results suggest that there are at least 2
      closely related precursors, GST-P(+)/GGT(-) and GST-P(+)/GGT(+) phenotypes, of
      preneoplastic foci in rat chemical hepatocarcinogenesis.

PMID- 15729700
TI  - A substantial proportion of microsatellite-unstable colon tumors carry TP53
      mutations while not showing chromosomal instability.
AB  - Chromosomal instability in colon tumors implies the presence of numerical and
      structural chromosome aberrations and is further characterized by the absence of
      microsatellite instability and the occurrence of KRAS and/or TP53 mutations. In a
      previous screening of 194 colon tumors for both microsatellite instability and
      TP53 mutation, we found 25 microsatellite-unstable tumors, in 9 (36%) of which,
      presumed to be chromosomally stable, there were TP53 mutations. This prompted us
      to investigate whether a TP53 mutation in these microsatellite-unstable tumors
      would be an indicator of chromosomal instability, that is, whether this would be
      a category of tumors showing both microsatellite and chromosomal instability. For
      chromosomal instability assessment, we performed array-comparative genomic
      hybridization analysis of tumor and control DNA extracted from formalin-fixed,
      paraffin-embedded stage III colon tumor specimens. The array consisted of 435
      subtelomere-specific BACs. We compared all but one (whose DNA was of bad quality)
      of the microsatellite-unstable TP53 mutation-containing tumors (8) with a
      similarly sized group of microsatellite-unstable tumors without TP53 mutation
      (11). Microsatellite-unstable tumors with a TP53 mutation showed on average 0.9
      aberrations (range 0-3) when assessed with this array system. Those without a
      TP53 mutation showed on average 0.7 aberrations (range 0-2). Thus, microsatellite
      unstable tumors showed few chromosomal abnormalities regardless of TP53 mutation
      status. Because, in our study, the microsatellite-stable tumors had on average
      3.4chromosomal abnormalities (range 0-7), a clear difference exists between
      microsatellite-unstable and -stable tumors. Because a substantial proportion of
      microsatellite-unstable colon tumors carry a TP53 mutation while showing
      relativelyfewchromosomal aberrations, a TP53 mutation in these tumors cannot be
      considered to be an indicator of chromosomal instability.

PMID- 15729701
TI  - Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated
      TORC1-MAML2 gene fusion.
AB  - Recent studies have shown that the t(11;19)(q21;p13) translocation in
      mucoepidermoid carcinomas and benign Warthin's tumors results in a fusion of the
      N-terminal CREB-binding domain of the cAMP coactivator TORC1 (a.k.a. MECT1 and
      WAMTP1) to the Notch coactivator MAML2. Here we show that a third tumor type,
      clear cell hidradenoma of the skin, also expresses this gene fusion. RT-PCR
      analysis of a clear cell hidradenoma with a t(11;19)(q21;p13) translocation
      revealed expression of a TORC1-MAML2 fusion transcript consisting of exon 1 of
      TORC1 fused to exons 2-5 of MAML2. Because the fusion was only detected in a
      single case, the frequency of this aberration in clear cell hidradenomas remains
      unknown. These results demonstrate that the t(11;19) in mucoepidermoid carcinoma,
      Warthin's tumor, and clear cell hidradenoma targets the same genes and results in
      identical gene fusions, indicating that at least subgroups of these glandular
      tumors evolve through activation of the same molecular pathways.

PMID- 15729702
TI  - EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12).
AB  - POU5F1(OCT3/4) is a sequence-specific transcription factor that is essential for
      keeping germ cells and embryonic stem cells in an immature and pluripotent
      status. In this article, we report that POU5F1 was fused to EWSR1 in a case of
      undifferentiated sarcoma derived from pelvic bone with chromosomal translocation
      t(6;22)(p21;q12). The EWSR1-POU5F1 chimera consists of exons 1-6 of EWSR1 and
      exons 2-5 and a part of exon 1 of POU5F1. The predicted amino acid sequence
      indicates that the chimera is composed of the N-terminal QSY domain of EWS that
      functions as a transcriptional activation domain and the C-terminal POU DNA
      binding domains derived from POU5F1. The t(6;22) tumor does not belong to any
      known categories of bone and soft-tissue tumors (BSTs). It is suggested that EWS
      POU5F1 may act as an oncogenic transcription factor and that its expression may
      contribute to undifferentiated and immature phenotypes of BST.

PMID- 15729703
TI  - Novel method for studying photolability of topical formulations: a case study of
      titanium dioxide stabilization of ketoprofen.
AB  - Sunlight may decompose active substances and excipients in pharmaceuticals. This
      may cause formulation problems as well as induce adverse skin reactions. The
      photodecomposition of topical preparations may occur on the skin surface, but
      also deeper in the skin after penetration of light into the viable tissues. The
      aim of the present study was to investigate whether microparticles of titanium
      dioxide could protect against photodecomposition using ketoprofen as a
      photolabile model substance. The results showed quality differences between
      titanium dioxide, where surface-coated particles were superior to pharmaceutical
      grades in reducing the degradation in vitro. The protective effect was also
      studied in humans. The skin was treated for 3 h with the gels and then exposed to
      ultraviolet (UV) light (11.7 J/cm2 UVA and 5.4 mJ/cm2 UVB). Layers of the stratum
      corneum were then removed by consecutive tape strippings and assayed for content
      of ketoprofen. The remaining amount was higher in the different stratum corneum
      compartments after treatment with a gel containing 4% coated titanium dioxide
      compared with a transparent gel. Thus, surface-coated microparticles of titanium
      dioxide may well be of clinical benefit in protecting photolabile drug substances
      against sunlight.

PMID- 15729704
TI  - Semaphorin/neuropilin signaling influences the positioning of migratory neural
      crest cells within the hindbrain region of the chick.
AB  - Within the hindbrain region, neural crest cell migration is organized into three
      streams that follow the segmentation of the neuroepithelium into distinct
      rhombomeric compartments. Although the streaming of neural crest cells is known
      to involve signals derived from the neuroepithelium, the molecular properties
      underlying this process are poorly understood. Here, we have mapped the
      expression of the signaling component of two secreted class III Semaphorins,
      Semaphorin (Sema) 3A and Sema 3F, at time points that correspond to neural crest
      cell migration within the hindbrain region of the chick. Both Semaphorins are
      expressed within rhombomeres at levels adjacent to crest-free mesenchyme and
      expression of the receptor components essential for Semaphorin activity by neural
      crest cells suggests a function in restricting neural crest cell migration. By
      using bead implantation and electroporation in ovo, we define a role for both
      Semaphorins in the maintenance of neural crest cell streams in proximity to the
      neural tube. Attenuation of Semaphorin signaling by expression of soluble
      Neuropilin-Fc resulted in neural crest cells invading adjacent mesenchymal
      territories that are normally crest-free. The loss or misguidance of specific
      neural crest cell populations after changes in Semaphorin signaling also affects
      the integration of the cranial sensory ganglia. Thus, Sema 3A and 3F, expressed
      and secreted by the hindbrain neuroepithelium contributes to the appropriate
      positioning of neural crest cells in proximity to the neural tube, a process
      crucial for the subsequent establishment of neuronal connectivity within the
      hindbrain region.

PMID- 15729705
TI  - Partially crystalline systems in lyophilization: II. Withstanding collapse at
      high primary drying temperatures and impact on protein activity recovery.
AB  - In an accompanying article we have described the construction of the water-rich
      sections of raffinose-glycine-water and trehalose-glycine-water state diagrams.
      In this study, we use the information obtained from the state diagrams to
      identify the minimum weight fraction of the crystalline component in glycine
      carbohydrate systems necessary to withstand collapse at high primary drying
      temperatures. We also determine the impact of primary drying, substantially above
      T'g, on the recovery of lactate dehydrogenase (LDH) activity. Ambient and
      variable temperature X-ray powder diffractometry and differential scanning
      calorimetry were used to characterize the frozen and freeze-dried systems.
      Aqueous solutions with glycine to carbohydrate (raffinose pentahydrate or
      trehalose dihydrate) weight ratios ranging from 0.2 to 2.0 were freeze dried. The
      protein formulations contained 20 mM citrate buffer (pH 6.0) and LDH (20
      microg/mL). A glycine to anhydrous raffinose weight ratio >or=1.18 and a glycine
      to anhydrous trehalose weight ratio >or=1.56 were necessary to withstand
      macroscopic collapse in the system, when the primary drying was carried out at a
      product temperature at least 10 degrees C above the T'g. The recovery of LDH
      activity was almost complete in the reconstituted lyophile whether the primary
      drying was carried out above T'g (-10 degrees C) or below T'g (-32 degrees C).
      Thus, by judiciously combining crystalline and amorphous components, it was
      possible to primary dry at temperatures substantially above the T'g.

PMID- 15729706
TI  - Partially crystalline systems in lyophilization: I. Use of ternary state diagrams
      to determine extent of crystallization of bulking agent.
AB  - Two model ternary systems: water-glycine-raffinose and water-glycine-trehalose
      were investigated to determine the extent of glycine crystallization in frozen
      solutions. The use of such partially crystalline systems allows primary drying to
      be carried out substantially above the collapse temperature. Differential
      scanning calorimetry (DSC) and variable temperature X-ray diffractometry (XRD)
      were used to monitor phase transitions in frozen systems as well as to determine
      the T'g. Aqueous solutions containing different glycine to carbohydrate weight
      ratios were first cooled to -60 degrees C and then warmed to room temperature. In
      both raffinose and trehalose systems, when the initial glycine to sugar
      (raffinose pentahydrate or trehalose dihydrate) ratio was <1, glycine
      crystallization was not detected. When the ratio was >or=1, partial glycine
      crystallization was observed during warming. The presence of amorphous glycine
      caused the T'g to be substantially lower than that of the solution containing
      only the carbohydrate. To determine the extent of glycine crystallization, the
      solutions were annealed for 5 h just above the temperature of glycine
      crystallization. The T'g observed in the second warming curve was very close to
      that of the carbohydrate solution alone, indicating almost complete glycine
      crystallization. These studies enabled the construction of the water-rich
      sections of the raffinose-glycine-water and trehalose-glycine-water state
      diagrams. These diagrams consist of a kinetically stable freeze-concentrated
      solution and a doubly unstable glassy region, which readily crystallizes during
      cooling or subsequent warming. In addition, there is an intermediate region,
      where during the experimental timescale, there appears to be hindered glycine
      nucleation but unhindered crystal growth. To obtain substantially crystalline
      glycine in the frozen solutions, the glycine to carbohydrate ratios should be
      >or=1.

PMID- 15729707
TI  - Fluconazole distribution in rat dermis following intravenous and topical
      application: a microdialysis study.
AB  - The objective of this study was to investigate the skin distribution of
      fluconazole, a water-soluble antifungal agent, following intravenous (i.v.) and
      topical administration in the awake freely moving rat. Following i.v. bolus
      injection of fluconazole (10 mg/kg), a dual-site microdialysis sampling was
      performed in jugular vein and dermis in five rats. In addition, cutaneous
      absorption was studied by dermal microdialysis sampling following topical
      application of Diflucan Gel 0.5% to 12 rats. Fluconazole microdialysate
      concentrations were measured by on-line HPLC. To calibrate in vivo the probes, a
      fluorinated analog (UK-54737) of fluconazole was used as retrodialysis marker
      after demonstrating that recoveries were no different. Following i.v. bolus
      injection, fluconazole rapidly penetrates into the dermis. Cutaneous
      microdialysis sampling provided dermal concentrations of fluconazole, which were
      very similar to the unbound plasma concentrations determined by vascular
      microdialysis. The distribution equilibrium was rapidly achieved with a dermis-to
      plasma partition coefficient of 1.02+/-0.04 (n=5). Following topical application
      of 0.5 g of Diflucan Gel containing 0.5% of fluconazole, active unbound
      concentrations in dermis were measured by cutaneous microdialysis for 11 h after
      application. The area under the curve (AUC) of fluconazole in dermal dialysate
      was relatively constant to an implantation depth of approximately 350 microm.
      Below this depth, the AUC progressively decreased with increasing implantation
      depth of the probe. Finally, this study shows that cutaneous microdialysis is an
      effective and minimally invasive tool to evaluate the dermal pharmacokinetics of
      fluconazole following intravenous or topical administration.

PMID- 15729708
TI  - Mass spectral analyses of labile DOTA-NHS and heterogeneity determination of DOTA
      or DM1 conjugated anti-PSMA antibody for prostate cancer therapy.
AB  - Prostate specific membrane antigen (PSMA) is a well-characterized glycoprotein
      overexpressed on the surface of prostate cancer cells. The novel
      radiopharmaceutical 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid
      (DOTA) radiolabeled with Yttrium (90Y) or Indium (111In) conjugated with anti
      PSMA genetically engineered humanized monoclonal antibody (huJ591) has been
      investigated to target prostate cancer cells. The immunoconjugate of huJ591 with
      the analog of the cytotoxic drug maytansine, DM1 (N2'-deacetyl-N2'-(3-mercapto-1
      oxopropyl)-maytansine) has also been developed at Millennium Pharmaceuticals.
      Activation of the DOTA molecule, resulting in 1,4,7,10-tetraazacyclododecane
      N,N',N'',N'''-tetraacetic acid mono-(N-hydroxysuccinimidyl) ester (DOTA-NHS),
      allows conjugation with the anti-PSMA antibody through lysine residues in the
      antibody. The objectives of the study were to characterize the unstable chemical
      properties of DOTA-NHS before bioconjugation with huJ591, evaluate the binding
      profiles of DOTA to huJ591, and calculate trace metal elements (which may disturb
      90Y or 111In labeling efficacy to the DOTA-huJ591 conjugate). A novel LC/MS/MS
      (Liquid Chromatography/Mass Spectrometry/Mass Spectrometry) quantitation method
      was developed to monitor the stability of DOTA-NHS in solid form and its
      bioconjugation chemistry reactions. Meanwhile, metal analysis was quantified by
      Inductively Coupled Plasma Mass Spectrometry (ICP/MS) to estimate the amounts of
      trace metals in DOTA-NHS and ensure radiolabeling efficiency of the conjugate at
      the radiopharmacy. MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization Time
      of-Flight Mass Spectrometry) was used to identify levels of DOTA or
      DM1conjugation in DOTA-huJ591 and DM1-huJ591 conjugates, respectively.

PMID- 15729709
TI  - A functional glutathione S-transferase P1 gene polymorphism is associated with
      methamphetamine-induced psychosis in Japanese population.
AB  - Several lines of evidence suggest that oxidative stress plays a role in the
      mechanisms of action of methamphetamine (MAP) in the human brain. Given the role
      of glutathione S-transferases (GSTs) in the protection against oxidative stress,
      genes encoding the GSTs have been considered as candidates for association
      studies of MAP abuse. This study was undertaken to investigate the role of the
      functional polymorphism of GSTP1 gene exon 5 (Ile105Val) in the pathogenesis of
      MAP abuse. Genotyping for GSTP1 gene polymorphism exon 5 (Ile105Val) in 189 MAP
      abusers and 199 normal controls was performed by polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP). Association between GSTP1 gene
      polymorphism and clinical features (prognosis of psychosis (transient-type and
      prolonged-type), spontaneous relapse (positive and negative), and poly-substance
      abuse) of MAP abusers was evaluated. Significant differences in the frequency of
      both alleles (P = 0.026, odds ratio: 1.70, 95% confidence intervals (CI) 1.06
      2.72) and genotypes (P = 0.029) between MAP abusers and controls were detected.
      In particular, a significant difference in both genotype frequency (P = 0.013)
      and allele frequency (P = 0.014, odds ratio: 1.84, 95% CI 1.13-2.97) between MAP
      abusers with psychosis (transient-type and prolonged-type) and controls was
      detected. Our findings suggest that the polymorphism (Ile105Val) on exon 5 of the
      GSTP1 gene may contribute to a vulnerability to psychosis associated with MAP
      abuse in Japanese population.

PMID- 15729710
TI  - SNP genotyping using microsphere-linked PNA and flow cytometric detection.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) represent the most frequent
      form of genetic variations. Some of the most sensitive methods for SNP genotyping
      employ synthetic oligonucleotides, such as the peptide nucleic acid (PNA). We
      introduce a new method combining allele-specific hybridization, PNA technology,
      and flow cytometric detection. We tested the design by genotyping a Danish basal
      cell carcinoma cohort of 80 individuals for an A/C SNP in exon 6 of the XPD gene.
      METHODS: Genomic DNA was amplified by a two-step polymerase chain reaction (PCR)
      in the presence of fluorescein-dyed primers and fluorescein-12-dUTP. The allele
      specific PNA molecules were covalently coupled to carboxylated microspheres with
      and without rhodamine. Allele-specific hybridization between PCR products and
      immobilized PNA was carried out at 60 degrees C followed by flow cytometric
      detection. RESULTS: We present a fully functional two-bead genotyping system
      based on PNA capture and flow cytometric detection used for the correct and fast
      regenotyping of a Danish basal cell carcinoma cohort. CONCLUSIONS: This new assay
      presents a simple, rapid, and robust method for SNP genotyping for laboratories
      equipped with a standard flow cytometer. Moreover, this system offers potential
      for multiplexing and will be operational for middle-scale genotyping.

PMID- 15729711
TI  - Further analysis of microsatellite marker in the BDNF gene.

PMID- 15729712
TI  - Identification of B and T cells in human spleen sections by infrared
      microspectroscopic imaging.
AB  - BACKGROUND: Infrared spectroscopy probes the chemical composition and molecular
      structure of complex systems such as tissue and cells. Infrared spectroscopic
      imaging combines this spectral information with lateral resolution near the
      single-cell level. We analyzed whether this method is competitive with classic
      immunohistochemical methods for immunologic tissue and cells. METHODS: We
      recorded infrared microspectroscopic mapping datasets with a 90- x 90-microm2
      aperture from a 3- x 3-mm2 unstained tissue area of human spleen. A secondary
      follicle containing a germinal center and a T zone were studied in more detail by
      infrared microspectroscopic imaging with lateral resolution near 5 mum. The
      results were compared with consecutive sections stained by immunoglobulin D
      antibodies. T and B lymphocytes were extracted from human blood and served as
      independent test samples. RESULTS: Cluster analysis of infrared datasets produced
      images that distinguished anatomical features such as primary and secondary
      follicles, T zones, arteries, and spleen red pulp. The assignments could be
      confirmed in consecutive sections by immunohistochemical staining. Main spectral
      variances between T and B lymphocytes in high-resolution measurements were
      attributed to specific spectral contributions of DNA and cytosol. CONCLUSIONS:
      Sensitivity and specificity of the infrared based methods are comparable to those
      of standard staining procedures for identification of B and T cells. However,
      infrared spectroscopic imaging can offer advantages in velocity, data throughput,
      and standardization because of minimal sample preparation. The results emphasize
      the potential of infrared spectroscopy as an innovative tool for the distinction
      of cell types, in particular in immunologic tissue.

PMID- 15729713
TI  - Development of a stereological method to measure levels of fluoropyrimidine
      metabolizing enzymes in tumor sections using laser scanning cytometry.
AB  - BACKGROUND: The enzymes thymidine phosphorylase (TP) and dihydropyrimidine
      dehydrogenase (DPD) influence the activities of fluoropyrimidine anticancer
      drugs. The sensitivity of cancer cells to capecitabine, which is an oral, tumor
      selective pre-prodrug of 5-fluorouracil may correlate better to the TP/DPD ratio
      than to levels of either enzyme alone. Our goal was to develop a quantitative
      immunofluorescent method for estimating the levels of TP, DPD, and their ratio in
      archival tumor sections. METHODS: Mouse anti-TP and rat anti-DPD monoclonal
      antibodies were used for parallel indirect immunofluorescent staining. The
      fluorescence was measured using a laser scanning cytometer (LSC; CompuCyte,
      Cambridge, MA) in single cells and in sections prepared from cell lines and a
      human tumor. The phantom contouring feature of the LSC provided a stereologic
      approach for collecting the fluorescence intensity data from sections. RESULTS:
      The relative fluorescence intensities measured in single cells or in sections of
      the cell lines, using single or double labeling, were similar, supporting the
      suitability of phantom contouring and two-color staining. Sections of the T-24
      and ZR-75-1 cell lines placed on the same slide as the tumor section were used as
      internal standards for fluorescence measurements. The TP/DPD ratios measured in
      three cell lines correlated well with the cytotoxicity of 5'-deoxy-5
      fluorouridine measured in vitro, indicating that the measurements are related to
      the biological activity of the drug. CONCLUSIONS: Plotting the data as contour
      maps of the topologic distribution of fluorescence intensities in tumor sections
      allows subsequent histopathologic examination, which may reveal features of the
      tumors leading to high or low ratios of these enzymes. In addition, this method
      can be used for any drug target/metabolic system where the key components are
      known and suitable antibodies are available.

PMID- 15729714
TI  - Na+/H+ exchanger activity is increased in doxorubicin-resistant human colon
      cancer cells and its modulation modifies the sensitivity of the cells to
      doxorubicin.
AB  - Multidrug resistant (MDR) tumor cells exhibit an altered pH gradient across
      different cell compartments, which favors a reduced intracellular accumulation of
      antineoplastic drugs and a decreased therapeutic effect. In our study, we have
      observed that the activity and expression of Na+/H+ exchanger (NHE), which is
      involved in the homeostasis of intracellular pH (pHi), are increased in
      doxorubicin-resistant (HT29-dx) human colon carcinoma cells in comparison with
      doxorubicin-sensitive HT29 cells. The pH(i) was significantly higher in HT29-dx
      cells, which accumulated less doxorubicin than HT29 cells. The NHE inhibitor 5-(N
      ethyl-N-isopropyl)amiloride (EIPA) significantly reduced the pHi value and
      increased the intracellular accumulation of doxorubicin in both cell populations:
      in the presence of EIPA HT29-dx cells accumulated as much drug as control HT29
      cells. On the other hand, monensin, a Na+/H+ ionophore mimicking NHE activation,
      and phorbol 12-myristate 13-acetate (PMA), which stimulates NHE, significantly
      increased the pHi and decreased the drug accumulation in HT29 cells to values
      similar to those observed in control HT29-dx cells. EIPA potentiated the
      cytotoxic effect of doxorubicin in HT29 cells, and made HT29-dx cells as
      sensitive to the cytotoxic effect of the drug as control HT29 cells. Instead, PMA
      and monensin made HT29 cells as insensitive to doxorubicin as HT29-dx cells.
      These results suggest that in MDR cells the higher cytosolic pH is likely to
      decrease drug accumulation, and that such resistance can be reverted by
      inhibiting the NHE activity. This result opens the possibility to revert MDR with
      the clinical use of NHE inhibitors.

PMID- 15729716
TI  - Metalloproteinases and their inhibitors in tumor angiogenesis.
AB  - Angiogenesis is the process by which new blood vessels are formed from
      preexisting vasculature. It is an essential feature of the female reproductive
      cycle, embryonic development and wound repair. Angiogenesis has also been
      identified as a causal or contributing factor in several pathologies, including
      cancer, where it is a rate-limiting step during tumor progression. Matrix
      metalloproteinases (MMPs) are a family of soluble and membrane-anchored
      proteolytic enzymes that can degrade components of the extracellular matrix (ECM)
      as well as a growing number of modulators of cell function. Several of the MMPs,
      in particular the gelatinases and membrane-type 1 MMP (MT1-MMP), have been linked
      to angiogenesis. Potential roles for these proteases during the angiogenic
      process include degradation of the basement membrane and perivascular ECM
      components, unmasking of cryptic biologically relevant sites in ECM components,
      modulation of angiogenic factors and production of endogenous angiogenic
      inhibitors. This review brings together what is currently known about the
      functions of the MMPs and the closely related ADAM (a disintegrin and
      metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase with
      thrombospondin motifs) families in angiogenesis and considers how this
      information might be useful in manipulation of the angiogenic process, with a
      view to constraining tumor progression.

PMID- 15729715
TI  - Transcriptional activation of survivin through the NF-kappaB pathway by human T
      cell leukemia virus type I tax.
AB  - Survivin, a unique member of the inhibitor of apoptosis protein family, is
      overexpressed in many cancers and considered to play an important role in
      oncogenesis. We previously reported the survivin expression profile in ATL, a CD4
      positive T-cell malignancy caused by HTLV-I. HTLV-I Tax is thought to play an
      important role in immortalization of T cells. We have shown also that the
      expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis
      induced by deprivation of IL-2 and converted its growth from being IL-2 dependent
      to being IL-2 independent through the NF-kappaB pathway. In our study, we
      demonstrate that constitutive expression of survivin was associated with
      resistance to apoptosis after IL-2 deprivation in Tax-expressing CTLL-2 cells.
      Transient transfection assays showed that survivin promoter was transactivated by
      Tax, via the activation of NF-kappaB. Pharmacological NF-kappaB inhibition
      resulted in suppression of survivin expression and caused apoptosis of Tax
      expressing CTLL-2 cells. Our findings suggest that activated NF-kappaB signaling
      contributes directly to malignant progression of ATL by preventing apoptosis,
      acting through the prosurvival protein survivin.

PMID- 15729717
TI  - Retinoid-related molecule AGN193198 potently induces G2M arrest and apoptosis in
      bladder cancer cells.
AB  - The novel synthetic retinoid-related molecule 4-[3-(1-heptyl-4,4-dimethyl-2-oxo
      1,2,3,4-tetrahydroquinolin-6-yl)-3-oxo-propenyl]benzoic acid (AGN193198) neither
      binds effectively to retinoic acid receptors (RARs) and retinoid X receptors
      (RXRs) nor transactivates in RAR- and RXR-mediated reporter assays. Even so,
      AGN193198 is potent in inducing apoptosis in human prostate and breast carcinoma
      cells (Keedwell et al., Cancer Res 2004;64:3302-12). Here, we extend these
      findings to show that AGN193198 potently and rapidly induces apoptosis in bladder
      carcinoma cell lines. One micromolar of AGN193198 completely abolished the growth
      of the transitional cell carcinoma lines UM-UC-3 and J82, and the squamous cell
      carcinoma line SCaBER; the transitional cell papilloma line RT-4 was slightly
      less sensitive to the growth inhibitory effect of AGN193198. Treated cells
      accumulated in the G2M phase of the cell cycle. This was accompanied by
      apoptosis, as revealed by staining cells for exposure of phosphatidylserine at
      their surface (binding of Annexin V) and FACS analysis of propidium iodide
      labeled cells. As reported for prostate cancer cells, AGN193198 provoked rapid
      activation of caspases-3 (by 6 hr), -8 (by 16 hr) and -9 (by 6 hr) in bladder
      cancer cells. These findings suggest that AGN193198 and related compounds, whose
      mechanism of action does not appear to involve RARs and RXRs, may be useful in
      the treatment of bladder cancer.

PMID- 15729718
TI  - BRAF mutation associated with dysregulation of apoptosis in human colorectal
      neoplasms.
AB  - To understand the role of BRAF dysfunction in the carcinogenesis and
      progression/development of colorectal tumors, the authors investigated genetic
      alterations in the BRAF gene in human colorectal neoplasms as well as the effects
      of an RAS inhibitor in BRAF-mutant cells. Seven colon cancer cell lines and 116
      colorectal tumors (34 adenomas and 82 adenocarcinomas) were analyzed. Genetic
      alterations in the BRAF and K-ras genes were examined using polymerase chain
      reaction-single strand conformation polymorphism and direct sequencing analyses.
      The growth-inhibitory and apoptosis-inducing effects of the FTI-277 RAS inhibitor
      in colon cancer cell lines were analyzed as well. An immunohistochemical study
      was also performed to investigate the correlations between the clinicopathologic
      parameters involved in the Ki-67 labeling index and the number of apoptotic
      bodies in tumor cells. FTI-277 did not suppress the proliferation of BRAF-mutant
      cells (WiDr and TCO), but remarkably inhibited the growth of K-ras mutant cells
      (LoVo). Interestingly, LoVo cells underwent apoptosis by FTI-277 in a dose
      dependent manner, whereas WiDr cells were resistant to this agent. In tumor
      samples, BRAF mutations were found in 1 (3.0%) of 33 adenomas and 6 (7.2%) of 83
      adenocarcinomas. No tumor exhibited mutations in both the BRAF and K-ras genes.
      Neither BRAF nor K-ras mutations correlated with the Ki-67 labeling index
      immunohistochemically. However, the number of apoptotic bodies was significantly
      decreased in the BRAF-mutant tumors. Mutation in the BRAF gene may contribute to
      colorectal carcinogenesis by upregulating the antiapoptotic role of the
      RAS/RAF/MEK/ERK pathway.

PMID- 15729719
TI  - Biosynthesis of polyhydroxyalkanoate (PHA) copolymer from fructose using wild
      type and laboratory-evolved PHA synthases.
AB  - Eleven laboratory-evolved polyhydroxyalkanoate (PHA) synthases which originated
      from Pseudomonas sp. 61-3 enzyme (PhaC1(Ps)), together with the wild-type enzyme,
      were applied for PHA synthesis from fructose using Ralstonia eutropha PHB(-)4 as
      a host strain. The evolved PhaC1(Ps) mutants had amino acid substitution(s) at
      position 325 and/or position 481. In these mutants, serine-325 (S325) was
      replaced by cysteine (C) or threonine (T), while glutamine-481 (Q481) was
      replaced by lysine (K), methionine (M) or arginine (R). All recombinant strains
      harboring the genes of the evolved PhaC1(Ps) mutants produced a significantly
      increased amount of PHA (55-68 wt.-%) compared with the one harboring the wild
      type gene (49 wt.-%). Particularly, those evolved PhaC1(Ps) mutants having
      multiple amino acid substitutions showed higher activities for PHA synthesis.
      Characterization of the PHA by NMR spectroscopy revealed that they were
      copolymers consisting of (R)-3-hydroxybutyrate (98-99 mol-%) and medium-chain
      length comonomers (1-2 mol-%). This study also confirmed that amino acid
      substitution at position 481 in PhaC1(Ps) led to an increasing molecular weight
      of PHA. The number-average molecular weight (Mn) of PHA (Mn = 240,000)
      synthesized by the evolved PhaC1(Ps) (Q481K) mutant was 4.6-fold greater than
      that (Mn = 52,000) synthesized by the wild-type enzyme.

PMID- 15729720
TI  - Improved anti-inflammatory and pharmacokinetic properties for superoxide
      dismutase by chemical glycosidation with carboxymethylchitin.
AB  - O-carboxymethylchitin (molecular weight = 1.07 x 10(5), degree of
      carboxymethylation = 80%, degree of N-acetylation = 91%) was chemically attached
      to superoxide dismutase by the formation of amide linkages through a carbodiimide
      catalyzed reaction. The glycosidated enzyme contained about 1.8 mole of
      polysaccharide per mole of protein and retained 57% of the initial catalytic
      activity. The anti-inflammatory activity of the enzyme was 2.4 times increased
      after conjugation with the polysaccharide. The modified superoxide dismutase
      preparation was remarkably more resistant to inactivation with H(2)O(2) and its
      plasma half-life time was prolonged from 4.8 min to 69 h.

PMID- 15729721
TI  - Alkaline and enzymatic degradation of L-lactide copolymers, 1. Amorphous-made
      films of L-lactide copolymers with D-lactide, glycolide, and epsilon
      caprolactone.
AB  - Films of poly(L-lactide) [i.e., poly(L-lactic acid) (PLLA)] and L-lactide
      copolymers with glycolide [P(LLA-GA)(81/19)], epsilon-caprolactone [P(LLA
      CL)(82/18)], D-lactide [P(LLA-DLA)(95/5), (77/23), and (50/50)] were prepared and
      a comparative study on the effects of comonomer type and content on alkaline and
      proteinase K-catalyzed hydrolyses of the films was carried out. The hydrolyzed
      films were investigated using gravimetry (weight loss and water absorption),
      differential scanning calorimetry (DSC), polarimetry, and gel permeation
      chromatography (GPC). To exclude the effects of molecular weight and
      crystallinity on the hydrolysis, the films were prepared from polymers having
      similar molecular weights and made amorphous by melt-quenching. It was found that
      incorporation of hydrophilic glycolide units in L-lactide chains raises the
      alkaline and enzymatic hydrolyzabilities, whereas incorporation of hydrophobic
      epsilon-caprolactone units in L-lactide chains reduces the alkaline and enzymatic
      hydrolyzabilities. On the other hand, incorporation of D-lactide units with the
      same hydrophilicity of L-lactide units increases the alkaline hydrolyzability but
      decreases the enzymatic hydrolyzability. The alkaline hydrolyzability of the
      films of L-lactide copolymers with different kinds of comonomers and P(LLA-DLA)
      with different D-lactide unit contents can be closely related to their
      hydrophilicity. On the other hand, the enzymatic hydrolyzability of L-lactide
      copolymer films with different kinds of comonomers is mainly determined by
      hydrophilicity, while that of P(LLA-DLA) films is determined by the averaged L
      lactyl and D-lactyl unit sequence lengths. The catalytic effect of proteinase K
      relative to that of alkali on the hydrolysis of P(LLA-DLA)(77/23) and P(LLA
      GA)(81/19) films normalized by that of PLLA was lower than unity, whereas the
      normalized relative catalytic effect of proteinase K on the hydrolysis of P(LLA
      CL)(82/18) film was higher than unity, meaning that despite low absolute alkaline
      and enzymatic hydrolyzability of the P(LLA-CL)(82/18) film, the catalytic effect
      of proteinase K may be maintained for this copolymer film, probably because of
      its blocky structure.

PMID- 15729722
TI  - Novel biomimetic surfactant: synthesis and micellar characteristics.
AB  - Novel biomimetic surfactants based on cholesterol as the hydrophobic segment and
      poly[2-(methacryloyloxy)ethyl phosphorylcholine] (pMPC) as the hydrophilic
      segment were synthesized in the present study by atom transfer radical
      polymerization (ATRP) of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) using a
      cholesterol-based macroinitiator. The association behavior of cholesterol-block
      poly[2-(methacryloyloxy)ethyl phosphorylcholine] (Chol-pMPCs) in aqueous solution
      was studied by (1)H NMR spectroscopy, fluorescence probe technique, and atomic
      force microscopy (AFM). The (1)H NMR spectrum of the polymer in CD(3)OD showed
      both the cholesterol group and the phosphorylcholine group while the cholesterol
      group did not appeared in the (1)H NMR spectrum of the polymer in D(2)O, which
      implied the formation of a micelle structure. Fluorescence excitation spectra of
      a pyrene probe solubilized in the aggregates of Chol-pMPCs suggested the presence
      of a critical micelle concentration (cmc) in water. The critical micelle
      concentrations of the polymers CMPC10, CMPC20 and CMPC40 were determined to be
      7.27 x 10(-3), 13.47 x 10(-3), and 20.77 x 10(-3) mg . mL(-1), respectively. AFM
      images of the aggregates on mica suggested that the pMPC block formed the
      biocompatible micelle coronas and the cholesterol block formed the hydrophobic
      micelle cores. These new biomimetic diblock copolymers were evaluated as
      "stealthy" nanocapsules for the delivery of hydrophobic drugs. The anti-cancer
      drug adriamycin (ADR) was chosen as a hydrophobic drug to be incorporated into
      the inner core of the micelles and the morphology of the drug-loaded micelles
      were observed by AFM.

PMID- 15729723
TI  - Fabrication of metal-semiconductor nanowire heterojunctions.

PMID- 15729724
TI  - Palladium-catalyzed asymmetric iodination of unactivated C-H bonds under mild
      conditions.

PMID- 15729725
TI  - Development of the vasculature in "pushing-type" liver metastases of an
      experimental colorectal cancer.
AB  - A mechanism for stroma formation (development of vasculature and supportive
      connective tissue) is suggested in an experimental "pushing-type" colorectal
      carcinoma liver metastasis model. The key element is the appearance of smooth
      muscle actin (SMA)-positive cells and the sinusoidal lakes at the border of the
      metastases. These lakes are the consequence of the disappearance ('stepping back'
      of hepatocytes from the border zone, resulting in the fusion of partially
      capillarized sinusoids. The growing tumor incorporates SMA-expressing cells and
      sinusoidal lakes. SMA-positive cells produce collagenous matrix, whereas the
      lakes become the central vessels within the connective tissue columns. Formation
      of these columns within the tumor is a consequence of the compression atrophy of
      the base of the incorporated liver tissue, leading to partial separation of the
      innermost part of the invagination containing functional vessel(s) from the
      surrounding liver.

PMID- 15729726
TI  - Effect of differences in cancer cells and tumor growth sites on recruiting bone
      marrow-derived endothelial cells and myofibroblasts in cancer-induced stroma.
AB  - Cancer-stromal interaction is well known to play important roles during cancer
      progression. Recently we have demonstrated that bone marrow-derived vascular
      endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the
      human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of
      the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10
      kinds of human cancer cell line were implanted into the subcutaneous tissue of
      the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG
      1-/- beta-gal Tg or RAG-1-/- GFP Tg). The recruitment frequency of BMD-VE (%BMD
      VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV),
      microvessel density (MVD) and stromal proportion (%St)] were measured. The
      correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0
      to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both
      parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD
      VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the
      effect of tumor growth sites on the recruitment of the cells of interest, a human
      pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites:
      subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the
      subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%,
      19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively)
      and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction
      without recruitment of BMD-VE or -MF was observed in the tumors at of the liver,
      spleen and lung (%St = 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis
      identified the 29 genes that expression was especially up- or down-regulated in
      the cell line that induced an abundant stromal reaction. However they did not
      encoded the molecules that were directly involved in stromal cell recruitment
      (chemokines), differentiation (cytokines) or proliferation (growth factors).
      These results indicate that the recruitment of BMD-VE and -MF is required for
      stromal formation during cancer progression and that the cancer microenvironment
      is important in stromal reaction and the recruitment of BMD-VE and -MF.

PMID- 15729727
TI  - NTP-CERHR expert panel report on the reproductive and developmental toxicity of
      acrylamide.

PMID- 15729729
TI  - Comment on developmental toxicity evaluation of butylparaben in Sprague-Dawley
      rats.

PMID- 15729730
TI  - National Toxicology Program Center for the Evaluation of Risks to Human
      Reproduction: guidelines for CERHR expert panel members.

PMID- 15729731
TI  - Reduced risk of prostate cancer in men who are childless as compared to those who
      have fathered a child: a population based case-control study.
AB  - Androgens are believed to play a major role in the etiology of prostate cancer,
      but studies of sex-hormone exposure in relation to risk for prostate cancer have
      been inconclusive. Male fertility may be an indicator of long-term androgen
      status. To study the role of testicular function in prostate cancer development,
      we have assessed number of biological children in relation to risk for this
      malignancy. We carried out a population-based case-control study with
      retrospective ascertainment of cases occurring in Sweden between 1958-98. In
      total, 48,850 cases of prostate cancer were identified through the nation-wide
      Cancer Registry. For each case, one control, matched by year of birth, was
      randomly selected from the Swedish population. Information on offspring was
      obtained from the Swedish Multi-Generation Registry. We estimated odds ratios
      (OR) and 95% confidence intervals (CI) for the association between number of
      offspring and risk for subsequent prostate cancer. Being childless or having
      fathered one child only were associated with reduced risks for prostate cancer
      compared to having fathered 2 or more children (OR = 0.83; 95% CI = 0.81-0.86 and
      OR = 0.93; 95% CI = 0.90-0.96, respectively). There was no further change in risk
      associated with fathering of more than 2 children. The risk for prostate cancer
      is reduced among childless men. A dysfunctioning reproductive apparatus fueling
      to a lesser extent prostatic growth, could be a plausible mechanism of this
      association.

PMID- 15729732
TI  - Center for the evaluation of risks to human reproduction--the first five years.
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (NTP-CERHR) was established by the NTP and the National Institute of
      Environmental Health Sciences (NIEHS) in 1998 to address the impact of chemical
      exposures on human reproductive and developmental health and to serve as an
      environmental and reproductive health resource for government agencies and the
      general public. The purpose of this report is to provide an overview of the
      Center activities and a summary of NTP conclusions on chemicals evaluated during
      this time period. CERHR evaluations involve the critical review of reproductive,
      developmental, and other relevant toxicity data by independent panels of
      scientists. The products of these evaluations are expert panel reports. The
      public has opportunities to provide oral comments at the panel meeting and
      written comments on draft and final expert panel reports. The NTP evaluates these
      comments, the conclusions of the expert panel, and any new data not available at
      the time of the panel meeting, and prepares an NTP brief that describes in plain
      language the NTP's conclusions on the reproductive and developmental hazard from
      specified chemical exposures. The NTP brief, expert panel report, and public
      comments comprise the NTP monograph on the chemical. Monographs are sent to
      federal regulatory agencies, the NTP Executive Committee, and the NTP Board of
      Scientific Counselors, and are publicly available. Over the last five years,
      CERHR conducted expert panel evaluations on 14 chemicals. At this time, 13 panel
      reports have been published and 12 NTP-CERHR monographs have been issued.
      Additionally, CERHR conducted a 2-day workshop on the role of thyroid hormones in
      reproductive and developmental health.

PMID- 15729733
TI  - Klinefelter's syndrome (XXY) as a genetic model for psychotic disorders.
AB  - Males with an extra-X chromosome (Klinefelter's syndrome) frequently, although
      not always, have an increased prevalence of psychiatric disturbances that range
      from attention deficit disorder in childhood to schizophrenia or severe affective
      disorders during adulthood. In addition, they frequently have characteristic
      verbal deficits. Thus, examining brain magnetic resonance imaging (MRI) scans of
      these individuals may yield clues to the influence of X chromosome genes on brain
      structural variation corresponding to psychiatric and cognitive disorders. Eleven
      adult XXY and 11 age matched XY male controls were examined with a structured
      psychiatric interview, battery of cognitive tests, and an MRI scan. Ten of eleven
      of the XXY men had some form of psychiatric disturbance, four of whom had
      auditory hallucinations compared with none of the XY controls. Significantly
      smaller frontal lobe, temporal lobe, and superior temporal gyrus (STG) cortical
      volumes were observed bilaterally in the XXY men. In addition, diffusion tensor
      imaging (DTI) of white matter integrity resulted in four regions of reduced
      fractional anisotropy (FA) in XXY men compared with controls, three in the left
      hemisphere, and one on the right. These correspond to the left posterior limb of
      the internal capsule, bilateral anterior cingulate, and left arcuate bundle.
      Specific cognitive deficits in executive functioning attributable to frontal lobe
      integrity and verbal comprehension were noted. Thus, excess expression of one or
      more X chromosome genes influences both gray and white matter development in
      frontal and temporal lobes, as well as white matter tracts leading to them, and
      may in this way contribute to the executive and language deficits observed in
      these adults. Future prospective studies are needed to determine which gene or
      genes are involved and whether their expression could be modified with
      appropriate treatments early in life. Brain expressed genes that are known to
      escape inactivation on extra-X chromosomes would be prime candidates.

PMID- 15729735
TI  - Multiple acute effects on the membrane potential of PC12 cells produced by nerve
      growth factor (NGF).
AB  - We studied whether nerve growth factor (NGF) can affect the membrane potential
      and conductance of PC12 cells. We demonstrate that NGF depolarizes the membrane
      of PC12 cells within a minute and by using transfected NIH 3T3-Trk and -p75 cells
      we show that both the high affinity NGF receptor p140(trk) and the low affinity
      NGF receptor or p75(NGF) may be involved in the depolarization. Tyrosine kinase
      inhibitor, K252a, partially inhibited the depolarization, but two agents
      affecting intracellular calcium movements, Xestospongin C (XeC) and thapsigargin,
      did not. The early depolarization was eliminated in Na+ free solutions and under
      this condition, a 'prolonged' (> 2 min) hyperpolarization was observed in PC12
      cells in response to NGF. This hyperpolarization was also induced in PC12 cells
      by epidermal growth factor (EGF). Voltage clamp experiments showed that NGF
      produced a late (> 2 min) increase in membrane conductance. The Ca2+-dependent BK
      type channel blocker, iberiotoxin, and the general Ca2+-dependent K+ channel
      blocker, TEA, attenuated or eliminated the hyperpolarization produced by NGF in
      sodium free media. Under pretreatment with the non-selective cation channel
      blockers La3+ and Gd3+, NGF hyperpolarized the membrane of PC12 cells. These
      results suggest that three different currents are implicated in rapid NGF-induced
      membrane voltage changes, namely an acutely activated Na+ current, Ca2+-dependent
      potassium currents and non-selective cation currents.

PMID- 15729734
TI  - Genome screen for loci influencing age at onset and rate of decline in late onset
      Alzheimer's disease.
AB  - We performed an affected sib-pair (ASP) linkage analysis to test for the effects
      of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE)
      genotype on linkage to late-onset Alzheimer's disease (AD) in a sample comprising
      428 sib-pairs. We observed linkage of mean AAO to chromosome 21 in the whole
      sample (max LOD = 2.57). This came entirely from the NIMH sample (max LOD =
      3.62), and was strongest in pairs with high mean AAO (>80). A similar effect was
      observed on chromosome 2q in the NIMH sample (max LOD = 2.73); this region was
      not typed in the IADC/UK sample. Suggestive evidence was observed in the combined
      sample of linkage of AAO difference to chromosome 19q (max LOD = 2.33) in the
      vicinity of APOE and 12p (max LOD = 2.22), with linkage strongest in sib-pairs
      with similar AAO. Mean ROD showed suggestive evidence of linkage to chromosome 9q
      in the whole sample (max LOD = 2.29), with the effect strongest in the NIMH
      sample (max LOD = 3.58), and in pairs with high mean ROD. Additional suggestive
      evidence was also observed in the NIMH sample with AAO difference on chromosome
      6p (max LOD = 2.44) and 15p (max LOD = 1.87), with linkage strongest in pairs
      with similar AAO, and in the UK sample with mean ROD on chromosome 1p (max LOD =
      2.73, linkage strongest in pairs with high mean ROD). We also observed suggestive
      evidence of increased identical by descent (IBD) in APOE epsilon4 homozygotes on
      chromosome 1 (max LOD = 3.08) and chromosome 9 (max LOD = 3.34). The previously
      reported genome-wide linkage of AD to chromosome 10 was not influenced by any of
      the covariates studied.

PMID- 15729736
TI  - Normalization of multicolor fluorescence in situ hybridization (M-FISH) images
      for improving color karyotyping.
AB  - BACKGROUND: Multiplex or multicolor fluorescence in situ hybridization (M-FISH)
      is a recently developed cytogenetic technique for cancer diagnosis and research
      on genetic disorders. By simultaneously viewing the multiply labeled specimens in
      different color channels, M-FISH facilitates the detection of subtle chromosomal
      aberrations. The success of this technique largely depends on the accuracy of
      pixel classification (color karyotyping). Improvements in classifier performance
      would allow the elucidation of more complex and more subtle chromosomal
      rearrangements. Normalization of M-FISH images has a significant effect on the
      accuracy of classification. In particular, misalignment or misregistration across
      multiple channels seriously affects classification accuracy. Image normalization,
      including automated registration, must be done before pixel classification.
      METHODS AND RESULTS: We studied several image normalization approaches that
      affect image classification. In particular, we developed an automated
      registration technique to correct misalignment across the different fluor images
      (caused by chromatic aberration and other factors). This new registration
      algorithm is based on wavelets and spline approximations that have computational
      advantages and improved accuracy. To evaluate the performance improvement brought
      about by these data normalization approaches, we used the downstream pixel
      classification accuracy as a measurement. A Bayesian classifier assumed that each
      of 24 chromosome classes had a normal probability distribution. The effects that
      this registration and other normalization steps have on subsequent classification
      accuracy were evaluated on a comprehensive M-FISH database established by
      Advanced Digital Imaging Research
      (http://www.adires.com/05/Project/MFISH_DB/MFISH_DB.shtml). CONCLUSIONS: Pixel
      misclassification errors result from different factors. These include uneven
      hybridization, spectral overlap among fluors, and image misregistration.
      Effective preprocessing of M-FISH images can decrease the effects of those
      factors and thereby increase pixel classification accuracy. The data
      normalization steps described in this report, such as image registration and
      background flattening, can significantly improve subsequent classification
      accuracy. An improved classifier in turn would allow subtle DNA rearrangements to
      be identified in genetic diagnosis and cancer research.

PMID- 15729737
TI  - Neuropathology of the cerebral cortex observed in a range of animal models of
      prenatal cocaine exposure may reflect alterations in genes involved in the Wnt
      and cadherin systems.
AB  - Several recent reports show that the cerebral cortex in humans and animals with
      altered expressions of Wnt/cadherin network-associate molecules display
      cytoarchitectural abnormalities reminiscent of cortical dysplasias seen in some
      (mouse-, rat-, and monkey-based) animal models of prenatal cocaine exposure.
      Therefore, we employed oligo microarrays followed by real-time RT-PCR to compare
      expressions of genes involved in Wnt and cadherin systems in the cerebral wall of
      18-day-old (E18) fetuses from cocaine-treated (20 mg/kg cocaine, s.c., b.i.d., E8
      18) and drug-naive (saline, s.c.) mice. The pregnant mice chronically treated
      with cocaine in the above-described manner represent one of the animal models
      producing offspring with widespread cortical dysplasias. Out of more than 150
      relevant genes in the arrays, 32 were upregulated and 9 were downregulated in
      cocaine-exposed fetuses. The majority of these genes (30 out of 41) were
      similarly affected in the frontal and occipital regions of the cerebral wall. We
      also used Western immunoblotting to examine the ability of cocaine to regulate
      the protein levels of beta-catenin, the key functional component of both Wnt and
      cadherin systems. While the total cell levels of beta-catenin were increased
      throughout the cerebral wall of cocaine-exposed fetuses, its nuclear (gene
      transcription driving) levels remained unaltered. This suggests a transcription
      unrelated role for cocaine-induced upregulation of this protein. Overall, our
      findings point to an intriguing possibility that that cerebral cortical
      dysplasias observed in several animal models of prenatal cocaine exposure may be
      at least in part related to alterations in the Wnt/cadherin molecular network.

PMID- 15729738
TI  - Cortical GABAergic regulation of dopaminergic responses to psychological stress
      in the rat dorsolateral striatum.
AB  - The present study was undertaken to examine the possible involvement of cortical
      gamma-aminobutyric acid (GABA) neuronal mechanisms in the regional differences of
      dopamine (DA) response to psychological stress: contextual fear conditioning
      (CFC) in the rat prefrontal cortex (PFC) and dorsolateral striatum (DLS). Rats
      that received five footshocks (shock intensity, 0.5 mA; shock duration, 2 sec)
      were subjected to CFC and dynamic changes in DA and GABA in both PFC and DLS were
      examined using dual-probe microdialysis. Extracellular levels of DA in the PFC
      were enhanced during exposure to CFC, whereas the levels in the DLS were not
      affected by this stimulus. Extracellular levels of GABA in the PFC, but not in
      the DLS, were markedly enhanced by CFC. Freezing behavior observed during
      exposure to CFC was attenuated by the GABA(A) receptor antagonist bicuculline
      (10(-3) M), which was perfused into the PFC. Intracortical application of
      bicuculline (10(-3) M) furthermore caused sustained increases in DA levels in the
      DLS by CFC. These data suggest that cortical GABA(A) receptors contribute to
      modulation of DA release in the DLS in response to CFC. Thus, the GABAergic
      neuronal system in the PFC appears to play a key role in the regional differences
      of the DAergic response to psychological stress.

PMID- 15729739
TI  - Noradrenergic and dopaminergic effects of (+)-amphetamine-like stimulants in the
      baboon Papio anubis.
AB  - (+)-Amphetamine, (+/-)-ephedrine, and phentermine are commonly used appetite
      suppressants that release monoamines from nerve cells by acting as substrates for
      biogenic amine transporters. One key difference among the three drugs is their
      selectivity for norepinephrine (NE) release vs. dopamine (DA) release. The NE/DA
      selectivity ratios for these drugs as determined in vitro [(EC50 NE(-1))/(EC50
      DA(-1))] are (+/-)-ephedrine (18.6) > phentermine (6.7) > (+)-amphetamine (3.5).
      The in vitro data suggest that when administered in vivo, these stimulants might
      differ in their ability to release DA from nerve terminals in the brain. To test
      this hypothesis, noradrenergic effects (i.e., plasma NE) and dopaminergic effects
      (i.e., central DA release) were assessed when each drug was administered
      intravenously (1.5 mg/kg) to anesthetized baboons. Central DA release was
      determined via positron emission tomography using the method of [11C]raclopride
      displacement. In the present investigation, high doses of these stimulants
      increased plasma NE and DA in parallel, but only (+)-amphetamine released central
      DA from neurons and decreased plasma prolactin. None of the drugs altered plasma
      amine metabolite levels, indicating no inhibition of monoamine oxidase activity
      at the administered doses. Plasma drug levels measured in baboons were higher
      than those measured in human patients taking prescribed doses of the drugs.
      Viewed collectively, the present data indicate that typical clinical doses of
      phentermine and (+/-)-ephedrine may not release central DA in humans, a
      hypothesis that should ultimately be tested in controlled clinical studies.

PMID- 15729740
TI  - Specific in vitro binding of (S,S)-[3H]MeNER to norepinephrine transporters.
AB  - The aim of this study was to determine the selectivity of (S,S)-2-(alpha-(2
      methoxyphenoxy)benzyl)morpholine (MeNER) binding to norepinephrine transporters
      (NET). Quantitative autoradiography studies of NET binding were performed in
      brains of wildtype mice and those of mutant mice lacking one or two alleles of
      the NET gene. [3H]MeNER binding in the wildtype mouse brains was consistent with
      previously reported distributions of NET. Highest levels were found in the locus
      coeruleus, thalamus, hypothalamus, and bed nucleus of stria terminalis. Specific
      binding in these regions was approximately 50% in the heterozygous NET mice and
      negligible in the NET knockout mice. Binding in the wildtype mouse brains was
      displaced by the NET ligand, nisoxetine, but not by the serotonin or dopamine
      transporter blockers, citalopram or GBR 12935. [3H]MeNER displayed much higher
      affinity for NET than for SERT or DAT in homogenate binding studies. Each of
      these features supports the binding specificity of this candidate in vivo NET
      ligand.

PMID- 15729741
TI  - Access to health care resources in the UK: the case of care for arthritis.
AB  - The paper uses new and detailed data from a population sample of individuals with
      arthritis to examine the impact of objective measures of need for treatment and
      individual measures of socio-economic position on the distribution of public and
      private health care. The quality of the data and the range of explanatory factors
      are more detailed than previously used to study of the allocation of NHS care.
      The results indicate that broadly the NHS appears to meet its equity goal of
      equal care for equal medical need, though there is evidence that education
      increases the amount of resources received. The results also show the importance
      of the interaction between the public and private sectors in the UK.

PMID- 15729742
TI  - Prefrontal cortical cell firing during maintenance, extinction, and reinstatement
      of goal-directed behavior for natural reward.
AB  - The prefrontal cortex (PFC) is important for higher cognitive functioning and the
      processing of reward-related information. Here, electrophysiological recording
      procedures were used to examine cell firing in the PFC in rats (n = 12) during
      water reinforcement sessions consisting of three phases. In phase one
      (maintenance), animals pressed a lever (fixed ratio 1) for water reinforcement
      (0.05 ml/press) paired with an auditory stimulus. Of 62 neurons recorded during
      maintenance, 39 (63%) exhibited one of three types of patterned discharges
      relative to the reinforced response for water. Specifically, PFC neurons
      exhibited increases in firing rate within seconds preceding the response (type
      PR; n = 9 cells) or increases (type RFe; n = 16 cells) or decreases (type RFi; n
      = 14 cells) in firing rate immediately following response completion. The
      remaining neurons did not alter their firing profiles relative to the reinforced
      response (type nonphasic cells; n = 23 cells). In phase two (extinction), lever
      press responses had no programmed consequences (i.e., water reinforcement and the
      auditory stimulus were not presented). After 30 min of no responding, phase three
      (reinstatement) began, during which each lever press response was again
      associated with water reinforcement paired with the stimulus. Results indicate
      differential effects of extinction/reinstatement on cell firing rates and
      patterns dependent on cell type. These findings are discussed with respect to the
      adaptive nature of PFC activity during goal-directed behaviors for "natural"
      rewards, and are considered relative to prior studies that examined nucleus
      accumbens cell firing during a similar behavioral task.

PMID- 15729743
TI  - The analysis of incomplete cost data due to dropout.
AB  - Incomplete data due to premature withdrawal (dropout) constitute a serious
      problem in prospective economic evaluations that has received only little
      attention to date. The aim of this simulation study was to investigate how
      standard methods for dealing with incomplete data perform when applied to cost
      data with various distributions and various types of dropout. Selected methods
      included the product-limit estimator of Lin et al. the expectation maximisation
      (EM-) algorithm, several types of multiple imputation (MI) and various simple
      methods like complete case analysis and mean imputation. Almost all methods were
      unbiased in the case of dropout completely at random (DCAR), but only the product
      limit estimator, the EM-algorithm and the MI approaches provided adequate
      estimates of the standard error (SE). The best estimates of the mean and SE for
      dropout at random (DAR) were provided by the bootstrap EM-algorithm, MI
      regression and MI Monte Carlo Markov chain. These methods were able to deal with
      skewed cost data in combination with DAR and only became biased when costs also
      included the costs of expensive events. None of the methods were able to deal
      adequately with informative dropout. In conclusion, the EM-algorithm with
      bootstrap, MI regression and MI MCMC are robust to the multivariate normal
      assumption and are the preferred methods for the analysis of incomplete cost data
      when the assumption of DCAR is not justified.

PMID- 15729744
TI  - A meta-analysis of the MTHFR C677T polymorphism and schizophrenia risk.
AB  - Epigenetic mechanisms such as methylation of DNA, could lead to abnormal
      neurodevelopment and may be important in the etiology of schizophrenia. Maternal
      dietary folate intake may play a role in determining methylation levels. The
      MTHFR gene C677T polymorphism influences folate metabolism and intracellular
      availability of folate metabolites for methylation. We carried out a meta
      analysis of MTHFR C677T genotype and schizophrenia risk, and found that TT
      homozygotes had a significantly increased risk, OR 1.48 (1.18-1.86). This
      supports the hypothesis that folate status is a determinant of schizophrenia
      risk. Larger studies of this issue are required, together with studies of
      maternal genotype which could identify whether maternal folate status during
      pregnancy is important.

PMID- 15729745
TI  - Association analysis of monoamine genes with measures of depression and anxiety
      in a selected community sample of siblings.
AB  - Evidence indicates the genetic susceptibility to depression and anxiety is both
      overlapping and dimensional. In the current study, a quantitative phenotype had
      been created from several depression and anxiety-related measures in order to
      index this common genetic susceptibility (G). This has been studied in 119
      sibships comprising 312 individuals, selected for extreme scores on G, from a
      community-based sample of 34,371 individuals. In a pathway based candidate gene
      study, we examined five microsatellite markers located within or nearby to five
      serotonin system genes (5HT2C, 5HT1D, 5HT1B, TPH1, and MAOB). Statistical
      analysis, carried out using QTDT, gave a significant association with a
      microsatellite downstream of TPH1. Further analysis included a life-events
      composite as a co-variable, this lead to a stronger association of TPH1. To our
      knowledge, this is the first study to report an association of the 3' end of TPH1
      with continuous measures of depression and anxiety.

PMID- 15729746
TI  - Association between the serotonin transporter gene and alcohol consumption in
      social drinkers.
AB  - Relatively few studies have investigated the role of the 5HTT gene in
      intermediate phenotypes such as alcohol consumption in non-alcohol dependent
      populations. A recent study reported an association with alcohol consumption in a
      student population. We attempted to replicate these findings and extend on this
      work in a representative, ethnically homogenous, non-alcohol dependent sample of
      social drinkers in the United Kingdom. The short allele of the 5HTT gene was
      significantly associated with increased alcohol consumption (P = 0.03). There was
      suggestive evidence of a genotype-sex interaction (P = 0.04). Post-hoc tests
      indicated higher alcohol consumption in men with one or more copies of the short
      allele, while in women consumption was highest among heterozygotes compared to
      both homozygote groups. Age at time of data collection and cigarette consumption
      were entered as covariates. These results replicate recent previous findings and
      suggest a possibility that this association may differ in men and women.

PMID- 15729747
TI  - Reduction in tibial shaft fracture healing time with essential nutrient
      supplementation containing ascorbic acid, lysine, and proline.

PMID- 15729748
TI  - Homeopathy from the perspective of a surface chemist.

PMID- 15729749
TI  - Asian-American physicians distinguish between licensed acupuncturists and
      physicians who incorporate acupuncture into their practices.

PMID- 15729750
TI  - Controlled sedation for refractory suffering: part II.

PMID- 15729751
TI  - Disappointment in slow-down for biomedical funding.

PMID- 15729752
TI  - Inguinal hernia--laparoscopic or open repair? The case for open repair.

PMID- 15729753
TI  - Penetrating cardiac injury.

PMID- 15729754
TI  - Helping hands--a simple technique to ensure a secure sternal closure following
      open cardiac surgery.

PMID- 15729755
TI  - The lifting of substernal goitres using a Fogarty catheter.

PMID- 15729756
TI  - The use of pulsed-lavage in severe peritonitis.

PMID- 15729757
TI  - An effective abdominal washout system.

PMID- 15729758
TI  - Parastomal hernia repair: a new technique.

PMID- 15729759
TI  - Catheterisation in a large inguinoscrotal hernia.

PMID- 15729760
TI  - Oviposition strategies of conifer seed chalcids in relation to host phenology.
AB  - Insects are considered the most important predators of seed cones, the female
      reproductive structures of conifers, prior to seed dispersal. Slightly more than
      100 genera of insects are known to parasitize conifer seed cones. The most
      diverse (i.e., number of species) of these genera is Megastigmus (Hymenoptera:
      Torymidae), which comprises many important seed pests of native and exotic
      conifers. Seed chalcids, Megastigmus spp., lay eggs inside the developing ovules
      of host conifers and, until recently, oviposition was believed to occur only in
      fertilized ovules. Ovule development begins just after pollination, but stops if
      cells are not fertilized. The morphological stage of cone development at the time
      of oviposition by seed chalcids has been established for many species; however,
      knowledge of ovule development at that time has been documented for only one
      species, M. spermotrophus. Megastigmus spermotrophus oviposits in Douglas-fir
      ovules after pollination but before fertilization. Unlike the unfertilized
      ovules, those containing a M. spermotrophus larva continue to develop, whether
      fertilized or not, stressing the need to broaden our understanding of the insect
      plant interactions for this entire genus. To achieve this task, we reviewed the
      scientific literature and assembled information pertaining to the timing of
      oviposition and to the pollination and fertilization periods of their respective
      host(s). More specifically, we were searching for circumstantial evidence that
      other species of Megastigmus associated with conifers could behave (i.e.,
      oviposit before ovule fertilization) and impact on female gametophyte (i.e.,
      prevent abortion) like M. spermotrophus. The evidence from our compilation
      suggests that seed chalcids infesting Pinaceae may also oviposit before ovule
      fertilization, just like M. spermotrophus, whereas those infesting Cupressaceae
      seemingly oviposit after ovule fertilization. Based on this evidence, we
      hypothesize that all species of Megastigmus associated with Pinaceae can oviposit
      in unfertilized ovules, whereas those exploiting Cupressaceae cannot, and thus
      oviposit only in already fully developed fertilized seeds. Furthermore, we
      predict that the presence of a larva in unfertilized ovules of all Pinaceae will
      influence the development of the female gametophyte by preventing its abortion.
      This influence on the Pinaceae can be interpreted as an ability to parasitize any
      of the potential seeds present in a seed cone, and as such represents a much more
      efficient oviposition strategy than searching and locating only fertilized seeds.
      Concomitantly, this ability has likely led to an overestimation of the impact of
      the species of seed chalcid infesting Pinaceae on seed production.

PMID- 15729761
TI  - Spectacular Batesian mimicry in ants.
AB  - The mechanism by which palatable species take advantage of their similarity in
      appearance to those that are unpalatable, in order to avoid predation, is called
      Batesian mimicry. Several arthropods are thought to be Batesian mimics of social
      insects; however, social insects that are Batesian mimics among themselves are
      rare. In Malaysia we found a possible Batesian mimic in an arboreal ant species,
      Camponotus sp., which was exclusively observed on foraging trails of the
      myrmicine ant Crematogaster inflata. The bright yellow and black colouring
      pattern, as well as the walking behaviour, were very similar in both species. We
      observed general interactions between the two species, and tested their
      palatability and the significance of the remarkably similar visual colour
      patterns for predator avoidance. Prey offered to C. inflata was also eaten by
      Camponotus workers in spite of their being attacked by C. inflata, indicating
      that Camponotus sp. is a commensal of C. inflata. An experiment with chicks as
      potential predators suggests that Camponotus sp. is palatable whereas C. inflata
      is unpalatable. After tasting C. inflata, the chicks no longer attacked
      Camponotus sp., indicating that Camponotus sp. is a Batesian mimic of
      Crematogaster inflata.

PMID- 15729763
TI  - Bonitasaura salgadoi gen. et sp. nov.: a beaked sauropod from the Late Cretaceous
      of Patagonia.
AB  - Ornithischian and theropod dinosaurs were morphologically diverse during the
      Cretaceous. In contrast, sauropods were relatively more conservative. The anatomy
      of Bonitasaura salgadoi, a new 9-m titanosaurian sauropod from Upper Cretaceous
      beds of Patagonia, suggests that sauropod anatomical diversity would have
      included unexpected items. Its unusual, rectangular lower jaw possesses narrow,
      anteriorly restricted teeth and shows evidence of a sharp keratinous sheath over
      the nondentigerous region that probably worked to guillotine plant material. This
      discovery definitely demonstrates that titanosaurs acquired a mandibular
      configuration similar to that of some basal diplodocoids, as had already been
      suggested by the lower jaw of the controversial genus Antarctosaurus. This oral
      configuration, plus the beak-like structure and the skull shape, resemble some
      traits more commonly seen in Laurasian ornithischians, mostly unexpressed in
      southern continents. A high sauropod morphological diversity seems to be in
      agreement with the poorly represented ornithischian clades of the southern
      hemisphere.

PMID- 15729762
TI  - Tail loss and thermoregulation in the common lizard Zootoca vivipara.
AB  - Tail autotomy in lizards is an adaptive strategy that has evolved to reduce the
      risk of predation. Since tail loss reduces body mass and moving ability-which in
      turn are expected to influence thermal balance-there is potential for a trade-off
      between tail autotomy and thermoregulation. To test this hypothesis, we studied a
      common lizard (Zootoca vivipara) population at high latitude, inhabiting a high
      cost thermal environment. Z. vivipara is a small, non-territorial lizard known as
      a very accurate thermoregulator. We made two predictions: (1) the reduced body
      weight due to tail loss results in faster heating rate (a benefit), and (2) the
      reduction in locomotor ability after tail loss induces a shift to the use of
      thermally poorer microhabitats (a cost), thus decreasing the field body
      temperatures of active lizards. We did not find any effect of tail loss on
      heating rate in laboratory experiments conducted under different thermal
      conditions. Likewise, no significant relationship between tail condition and
      field body temperatures, or between tail condition and thermal microhabitat use,
      were detected. Thus, our results suggest that tail autotomy does not influence
      the accuracy of thermoregulation in small-bodied lizards.

PMID- 15729764
TI  - [Spigelian hernia].

PMID- 15729766
TI  - Temporary crowns: repositioning key as a new technical approach in the clinical
      relining phase.
AB  - To accomplish prosthetic rehabilitation, a series of important procedures must be
      followed to achieve the correct final prosthetic outcome. The protocol presented
      in this article proposes a different approach that involves relining the
      temporary crowns during the provisional phase by means of a repositioning key.
      This approach is especially useful for therapeutic provisional restoration in
      patients with temporomandibular joint disorders. CLINICAL SIGNIFICANCE: The
      methodology presented allows the exclusion of arbitrary repositioning in the
      three-dimensional space of the provisional restoration, considering it as a fixed
      starting point. Our results tend to emphasize this technique not only for the
      ease of use, but also for the shorter time required for the occlusal fitting
      procedures in the final finishing phases.

PMID- 15729767
TI  - Opinion on Directive 98/44/EC on the legal protection of biotechnical inventions,
      and its implementation in Sweden.
AB  - The following statement is the formal opinion by the Swedish National Council on
      Medical Ethics concerning the implementation of Directive 98/44/EC of the
      European Parliament concerning legal protection of biotechnical inventions, and
      the implications and implementation of this Directive in Sweden.

PMID- 15729768
TI  - The treatment of adolescents in Australian general practice.

PMID- 15729769
TI  - Patient education. How to use an EpiPen. A single use, preloaded adrenaline
      device.

PMID- 15729770
TI  - Established and emerging roles of liposomal anthracyclines in oncology.
      Introduction.

PMID- 15729771
TI  - 2-Mercaptoimidazoles, a new class of potent CCR2 antagonists.
AB  - We describe the synthesis and SAR of a new class of CCR2 antagonists based on 2
      mercaptoimidazole scaffold. The initial lead 1a was optimized to the 3,4
      disubstituted analogues 1p-(S) and 1q-(S), which have IC(50) values in the MCP-1
      induced Ca-flux below 0.01 microM.

PMID- 15729772
TI  - The ionic hydrogen bond.

PMID- 15729774
TI  - NMR and QSAR studies on the transacylation reactivity of model 1beta-O-acyl
      glucuronides. I: design, synthesis and degradation rate measurement.
AB  - 1. The products arising from intramolecular acyl migration reactions of drug
      ester glucuronides are reactive towards cellular proteins and can potentially
      cause toxic side-effects. The relationship between molecular structure and the
      degradation rates (kd) of 1beta-O-acyl glucuronides were investigated
      systematically using a series of model compounds based on 4-substituted benzoic
      acids. 2. A rational method for selecting suitable compounds for inclusion was
      used and 10 glucuronide esters, predicted to produce a wide range of
      transacylation rates, were synthesized via a simple "one-pot" method using an
      imidazolide intermediate. The 10 substituents, where X = NO2, CN, I, Br, F, H,
      nPr, Et, OMe, O-nPr, had degradation rate half-lives (t1/2 = loge(2)/kd) ranging
      from 0.9 to 106.6 h. The reactions resulted in mixtures, which predominantly
      consisted of the desired 1beta-O-acyl glucuronides. 3. It was demonstrated that
      further purification was unnecessary for determination of kd of the synthetic
      1beta-O-acyl glucuronides. Degradation rates (kd) were calculated by following
      the disappearance of the 1H-NMR signal from the 1beta-anomeric proton of the
      glucuronic acid moiety as the reaction progressed in pH 7.4 buffer inside an
      nuclear magnetic resonance tube. Each measured degradation rate represents a
      pseudo-first-order rate constant, which is a combination of the transacylation
      rate (1beta to 2beta isomer) and the hydrolysis rate. 4. Degradation rates show a
      clear relationship with substituent properties, with half-life increasing as the
      substituent becomes more electron-donating, e.g. 4-nitro t1/2 = 0.9 h and 4
      propoxy t1/2 = 106.6 h.

PMID- 15729773
TI  - Use of the race concept in anthropometry.

PMID- 15729775
TI  - Half a billion and counting: the NHS's black hole revealed.

PMID- 15729776
TI  - On dealing with complaints.

PMID- 15729777
TI  - Food choice of tactile defensive children.
AB  - OBJECTIVE: We explored whether tactile defensive children have picky eating
      habits because fussy or picky eaters are a general problem to parents and
      different health professionals. METHODS: Children (n = 62) of both sexes, ages 3
      to 10 y, were assigned to an experimental tactile defensive (TD) group (n = 29)
      or a control non-TD group (n = 33). A questionnaire on eating habits was compiled
      and given to parents for completion during personal interviews (children were
      screened with a checklist and evaluated for tactile defensiveness with the Winnie
      Dunn Caregiver profile questionnaire). RESULTS: This research confirmed that the
      eating habits and food choices of TD and non-TD children differ significantly. TD
      children had a fair to poor appetite. They hesitated to eat unfamiliar foods, did
      not eat other people's houses, and refused certain foods because of the smell and
      temperature. They also had a problem eating vegetables. They often gagged and/or
      bit their inner lips and cheeks. The results showed a definite difference in the
      limited selection of foods that TD children chose and a pronounced aversion
      toward textures or consistencies, smells, and temperatures of food as compared
      with integrated children. CONCLUSIONS: Fussy or picky eaters should evaluated
      more widely than to treat only the feeding problem. Tactile or oral defensiveness
      can be treated. This report underlines the team approach of health professionals.

PMID- 15729778
TI  - Data briefing. Economic growth and NHS spending.

PMID- 15729779
TI  - On US public health.

PMID- 15729781
TI  - Working lives. Organisational development: a modest claim for change.

PMID- 15729780
TI  - An extramedullary foramen magnum cavernous malformation presenting with acute
      subarachnoid hemorrhage: case report and literature review.
AB  - OBJECTIVE AND IMPORTANCE: This case summarizes our experience with the first
      described intradural extramedullary cavernous malformation at the foramen magnum
      and reminds the neurosurgical community to consider cavernous malformations in
      the differential diagnosis for subarachnoid hemorrhage. CLINICAL PRESENTATION: A
      21-year-old man presented with an occipital headache, photophobia, nausea, neck
      stiffness, and fever of 10 days' duration. A lumbar puncture yielded a clear pink
      fluid with 300 leukocytes/mm3 (30% neutrophils and 65% lymphocytes) and 42,200
      erythrocytes/mm3, a protein count of 243 mg/dl, and a glucose count of 56 mg/dl.
      Computed tomography revealed a 1.5-cm right-sided dural-based mass of high
      attenuation that spanned the foramen magnum and a segment of the upper spinal
      canal. Magnetic resonance imaging showed a loculated, heterogeneously enhancing
      mass with a cystic component that slightly displaced the medulla to the left. An
      angiogram was negative for aneurysms and vascular malformations but did show an
      area of early filling and slow washout of the epidural venous plexus at the
      posterior canal margin of C1 and C2. INTERVENTION: A suboccipital craniectomy and
      C1 laminectomy were performed. Upon opening of the dura, an encapsulated mass was
      visualized. The lesion was located on the right lateral surface of the
      cervicomedullary junction and was entirely extraparenchymal. The mass was
      microsurgically dissected, and its associated venous malformation was left
      intact. The patient's postoperative course was uneventful, with a return to
      baseline function. Pathological examination confirmed the diagnosis of cavernous
      malformation. CONCLUSION: Our report not only presents a unique combination of
      pathological lesion, location, and presentation but also demonstrates that such
      lesions may be treated surgically with excellent results.

PMID- 15729782
TI  - Angioleiomyoma of the cavernous sinus: case report.
AB  - OBJECTIVE AND IMPORTANCE: Angioleiomyomas (ALMs) are relatively rare, benign,
      vascular soft tissue tumors that occur most frequently in the extremities of
      middle-aged individuals. To date, only two cases of intracranial ALMs have been
      described, both with little emphasis on the clinical, surgical, and radiological
      aspects. Neither of these reported cases of ALM involved the cavernous sinus.
      Furthermore, there is no previous intracranial ALM magnetic resonance imaging
      scan described in the literature. This report presents the first case of
      cavernous sinus ALM, emphasizing the clinical, radiological, and surgical
      aspects. CLINICAL PRESENTATION: A 52-year-old man had a 2-year history of
      horizontal diplopia and frontal headache. Facial numbness and impaired visual
      acuity in the previous 6 months were also reported. Physical examination revealed
      paralysis of right Cranial Nerves III, IV, and VI. A decrease in optical acuity
      was also noted. Computed tomographic and magnetic resonance imaging scans
      demonstrated a mass lesion located in the right cavernous sinus, which enhanced
      homogeneously with administration of intravenous contrast medium. INTERVENTION: A
      total resection was performed via a right frontotemporal craniotomy and a
      pretemporal approach with peeling of the middle fossa. The postoperative course
      was uneventful. Histological examination identified the ALM, with no recurrence
      noted during follow-up. CONCLUSION: It is unknown why intracranial ALMs have not
      been reported more frequently in the literature. Although ALMs are a rare
      occurrence, misinterpretation of this lesion may also have contributed to the
      lack of reported cases. Before surgery, ALMs can be distinguished from
      meningiomas and schwannomas but not from hemangiomas. The prognosis of
      intracranial ALM is good, as suggested in this case as well as the two previously
      reported cases.

PMID- 15729783
TI  - In memoriam: Harold M. Frost, M.D., Dr.Sc. Hon., orthopedist.

PMID- 15729784
TI  - Remembrance: G. Jeanette Thorbecke.

PMID- 15729785
TI  - Pictures of Episcopal hospital, Philadelphia, PA: part I (1851-1926).
AB  - The merit of images, often posed, often retouched, as historical documents has
      been debated by numerous scholars. Nonetheless, portraits, illustrations, and
      photographs form one of the more delightful avenues for recapturing elements of
      medical care as it was practiced in the past. Part one of this two-part photo
      essay records the first cycles of growth and contraction that characterized the
      history of one of Philadelphia's foremost medical institutions: The Hospital of
      the Protestant Episcopal Church of Philadelphia.

PMID- 15729786
TI  - Victor Satinsky (1912-1997) and the success of his partially occluding vascular
      clamp.

PMID- 15729787
TI  - Historical aspects of contemporary complementary medicine.

PMID- 15729788
TI  - Lithotripsy in America: transfer of the technique from Europe, 1824-1840.

PMID- 15729789
TI  - Memoir: W. Robert Penman, M.D., 1920-2000.

PMID- 15729790
TI  - The Samuel X Radbill collections.

PMID- 15729793
TI  - 'We are just kids': children within health care relationships.

PMID- 15729794
TI  - 'Sometimes they run away, that's how scared they feel': the peadiatric
      hospitalisation experiences of Indigenous families from remote areas of
      Australia.
AB  - Hospitalisation can be a traumatic experience for any child and family but the
      experience can be significantly more so for Indigenous parents and children from
      remote areas of Australia. Despite the importance of this issue for child and
      family health and for Indigenous health, the hospitalisation experiences of
      Indigenous families and children have received almost no research attention. This
      paper describes selected findings from a recently completed Honours research
      study which used the participatory and collaborative Indigenous research approach
      of Dadirri to explore this question. Following a brief description of the
      methodology of Dadirri, the paper presents the participating families' depictions
      of their experiences of 'Coming Down' and 'Being in Hospital', where they
      revealed the extent and effects of marked culture shock. The significant cultural
      differences between staff and Indigenous families contributed to the parents'
      sense of fear, powerlessness and isolation from their child, home community and
      culture. For these families this isolation was not merely geographic but
      intricately linked to their health and wellbeing.

PMID- 15729795
TI  - 'I know my body, I've lived in it all my life': therapy experiences of young
      people with disabilities.
AB  - Remedial surgery and other treatments are a common feature of disabled
      childhoods. These treatments are founded on notions of a normal:abnormal divide
      in which the task of health professionals is to bring such young people as close
      to societal concepts of normal as possible. Working with new paradigm disability
      and childhood research young people who are growing up with a disability have
      been able to contribute to our understanding from their perspectives. The young
      people identify the physical, social and emotional implications of remediation
      and identify a personal cost:benefit ratio. Questions of outcomes, definitions of
      success, and 'how much remediation is enough?' further complicate this. What may
      be perceived as a successful outcome by the health professional may not result in
      any functional gain for the young person. In discourses heavily influenced by
      health professional and parent perceptions the inclusion of the young people
      themselves contributes an additional dimension to our understanding.

PMID- 15729796
TI  - Fathers struggling for relevance in the care of their terminally ill child.
AB  - Children with terminal illness receive substantial amounts of care from their
      parents within their home, a palliative care facility or general hospital. Whilst
      there is a long history of research exploring child and family experiences and
      coping styles within these settings, the focus has not been on fathers'
      participation in care-giving. This phenomenon can be explained by traditional sex
      role socialisations whereby men are ostensibly conditioned as breadwinners and
      mothers remain embedded as the primary carers for children, particularly when
      illness arises. Nevertheless, nurses report that men do provide direct care
      giving or seek to be more involved in caring for their child. This literature
      review offers opportunities for health professionals to reflect on the
      significance of gender in parenting the terminally ill child and to develop
      empathy for men experiencing difficulties in their role as care-givers. As there
      is little literature available on this topic, this paper portrays men's
      experiences and importantly the barriers they encounter in meeting their desire
      to care. The approach provides a suitable basis for developing a research agenda
      to promote competencies and relevance for fathers in their role as care-giver.

PMID- 15729797
TI  - Development and evaluation of an intensive intervention program for children with
      a chronic health condition: a pilot study.
AB  - A range of developmental risk factors threatens the psychosocial well-being of
      children with a chronic health condition (CCHC). Early intervention and
      prevention programs are emerging as an effective response to improving individual
      and family coping mechanisms. In particular, efforts to address individual and
      family coping throughout the important pre-teen transitional ages for CCHC have
      gained popularity although their effectiveness has not been adequately
      demonstrated. We conducted a pre-post intervention study to evaluate an intensive
      intervention program for CCHC aged 10-14 years that aimed to enhance well-being.
      Twelve CCHC participated in a pilot 8-week intensive intervention program. At
      three month follow-up there was a significant increase in children's self esteem
      (t = 3.39, p < .01). There was a decrease in mean scores for anxiety and
      depression symptoms. Parental perceptions of the impact of the condition on the
      child reduced significantly (t = 2.37, p < .05). It was beyond the scope of the
      present study to conclusively evaluate the effectiveness of the intensive
      intervention program, however results show that it was a promising strategy to
      improve a range of outcomes for CCHC. Further research using a larger sample is
      needed to determine the ways in which this program influences psychosocial well
      being of CCHC and their families.

PMID- 15729798
TI  - Children of the 21st century: slipping through the net.
AB  - This article briefly explores the literature focusing on early childhood
      development, parenting and the provision of health services to young families. It
      highlights a number of reasons why some children with subtle developmental
      difficulties are not identified until school age. Relevant to child health nurses
      are: a changing focus on early childhood health issues; low repeat attendance at
      child health clinics, and the reluctance of parents to seek assistance; the
      impact of socio-economic status, cultural and ideological influences; the
      challenges presented in using complex screening tools; the difficulty in
      detecting subtle developmental problems; the lack of involvement of parents in
      decision-making; and, the reluctance of both professionals and parents to 'label'
      children. Drawing attention to these issues is essential for child health nurses
      who have the opportunity to provide effective and timely assistance to families
      and young children.

PMID- 15729799
TI  - Addressing the needs of children of parents with a mental illness: current
      approaches.
AB  - Children of parents with a mental illness have been identified as vulnerable to
      experiencing a variety of psychosocial effects arising from the impact of
      parental mental illness. Many children do not however, experience difficulties as
      a result of their parent's mental illness and are able to thrive despite what may
      be an adverse situation. Until recently there has been a lack of adequate service
      provision in Australia for these children and their families. Recent government
      initiatives have led to greater awareness and recognition of the needs of
      children whose parents have a mental illness, and key principles and actions have
      been developed to assist health services to adequately care for them. The aim of
      this paper is to overview the risk and protective factors that may impact on the
      psychosocial health children of parents with a mental illness, and provide me
      strategies that nurses in a range of health settings may use to assist families
      where parents have a mental illness.

PMID- 15729800
TI  - 'A last resort?' Impacts of Australian government refugee policy breaching the
      United Nations Convention on the Rights of the Child (1989).

PMID- 15729801
TI  - Family violence: walking the tight rope between maternal alienation and child
      safety.
AB  - Mothers are often alienated from their children when child abuse is suspected or
      confirmed, whether she is the primary abuser of the child or not. An abusive or
      violent partner often initiates the process of maternal alienation from children
      as a control mechanism. When the co-occurrence of maternal and child abuse is not
      recognised, nurses and health professionals risk further alienating a mother from
      her child/ren, which can have detrimental effects in both the short and long
      term. Evidence shows that when mothers are supported and have the necessary
      resources there is a reduction in the violence and abuse she and her children
      experience; this occurs even in situations where the mother is the primary abuser
      of her children. The family-centred care philosophy, which is widely accepted as
      the best approach to nursing care for children and their families, creates
      tension for nurses caring for children who are the victims of abuse as this care
      generally occurs away from the context of the family. This fragmented approach to
      caring for abused children can inadvertently undermine the mother-child
      relationship and further contribute to maternal alienation. This paper discusses
      the complexity of family violence for nurses negotiating the 'tight rope' between
      the prime concern for the safety of children and further contributing to maternal
      alienation, within a New Zealand context. The premise that restoration of the
      mother-child relationship is paramount for the long-term wellbeing of both the
      child/ren and the mother provides the basis for discussing implications for
      nursing practice.

PMID- 15729802
TI  - Raising families: urban women's experiences of requiring support.
AB  - Rapid social changes and the pressures of contemporary living have put families
      under increasing stress. Nurses have the potential to offer support for families
      experiencing stress. Therefore, it behoves nurses to develop a greater
      understanding of the stressors affecting families in contemporary Australia. This
      paper reports an exploratory descriptive study of urban women's experiences of
      dealing with difficult and demanding situations in their lives as mothers and
      family carers in contemporary Australian society, and explores women's
      experiences of seeking support for family issues. Participants' insights about
      the nature and availability of support for themselves and their families when in
      these stressful situations are revealed. Participants sought support from various
      personal networks, community and self help groups, and professional helpers.
      However, adequate support was not always available. Nurses have the potential to
      further develop their role in relation to providing support to women raising
      families.

PMID- 15729803
TI  - Managing family life while studying: single mothers' lived experience of being
      students in a nursing program.
AB  - Evidence suggests that single parent families are more likely to be affected by
      social problems associated with poor health and poverty. Single parent families
      are growing in number and are overwhelmingly headed by women. Despite their
      increasing number and their level of vulnerability, the lived experiences of
      single mothers have attracted little attention in the literature. Still little is
      known about many aspects of life as experienced by single mothers. Nursing is a
      profession that is dominated by women, and every year a number of single mothers
      enroll in undergraduate nurse education programs. Currently, there is little
      information about the experiences of women who are single mothers, undertaking a
      nursing degree in a university. This paper reports a study that explored the
      lived experiences of five single mother undergraduate nursing students. van
      Manen's phenomenological method informed the design and conduct of the study.
      Findings were grouped into the following themes: being exhausted all the time;
      being overwhelmed with worries; and being hopeful of the future. Findings of this
      study revealed that the single mothers' major health concerns were chronic
      tiredness and overwhelming worries. However, their being in the university was
      perceived as being health promoting and restoring to their self-esteem.
      Implications for educators, health providers and women's health services are
      drawn from the findings.

PMID- 15729805
TI  - Maternal and child health nurses: a vital link to the community for primiparae
      over the age of 35.
AB  - Australia, like other developed countries, is exhibiting a trend towards later
      childbearing and this trend has been particularly evident in the last three
      decades. Social trends of declining birth rates and small nuclear families mean
      that the contemporary adult has far less exposure to children than adults of
      former generations. Increasing female trends of employment and participation in
      higher education have also contributed to a postponement of childbearing, and
      more women than ever before are having a first baby over the age of 35 years.
      Mothering experiences for this group of women often occur in a situation of
      limited family or social support, geographical distancefrom family and with few
      links to the community. Together these factors make new mothering an isolating
      experience for some women. This paper reports on findings from a longitudinal
      qualitative study, outlining the importance of maternal & child health nurses in
      providing support and in facilitating links to the community for primiparae over
      the age of 35 years.

PMID- 15729804
TI  - Eating disorders: a qualitative analysis of the parents' journey.
AB  - Eating disorders are a major concern in Western society. The journey that parents
      undertake when their child has suffered from an eating disorder has been rarely
      reported. The aim of this research was to explore the parents' journey using in
      depth interviews. Twenty-two parents from New South Wales, Australia, volunteered
      to be interviewed as a result of advertisements placed in parent support
      organisation newsletters and by using a snowballing technique. Four aspects of
      the journey that the parents took when their child was ill are reported in this
      paper. The research findings are taken directly from the accounts provided by
      parents. These parents' stories will be of interest to health professionals
      working with families in the area of eating disorders.

PMID- 15729806
TI  - Child and family health nursing and early intervention.

PMID- 15729807
TI  - Obesity in pre-school chldren: issuse and challenges for community based child
      health nurses.
AB  - Childhood obesity is becoming a topical issue in both the health literature and
      the popular media and increasingly child health nurses are observing preschool
      children who appear to be disproportionately heavy for their height when plotted
      on standardized growth charts. In this paper literature related to childhood
      obesity in New Zealand and internationally is explored to identify current
      issues, and the implications of these issues for nurses in community based child
      health practice are discussed. Themes that emerged from the literature relate to
      the measurement of obesity, links between childhood and adult obesity and issues
      for families. A theme in the literature around maternal perception was of
      particular interest. Studies that investigated maternal perceptions of childhood
      obesity found that mothers identified their child as being overweight or obese
      only when it imposed limitations on physical activity or when the children were
      teased rather than by referring to individual growth graphs. The implications for
      nursing in the area of child health practice is discussed as nurses working in
      this area need an understanding of the complex and often emotive issues
      surrounding childhood obesity and an awareness of the reality of people's lives
      when devising health promotion strategies.

PMID- 15729808
TI  - Emergency contraception: a qualitative study of young women's experiences.
AB  - Emergency contraception has the potential to greatly reduce the number of
      unintended pregnancies. Experiences in the use of emergency contraception have
      rarely been reported in the literature. Thirteen young women (a subset of a
      larger study cohort), were individually interviewed in a variety of settings
      about their personal experiences in relation to the use of emergency
      contraception. A thematic analysis of the transcribed data was undertaken.
      Barriers and facilitators to its use are explicated using excerpts from
      individual interviews with participants. Some young women had positive
      experiences, however many experiences were negative and reflected difficulties
      with access and availability of emergency contraception, as well as poor provider
      attitudes. Positive experiences generally occurred where services were responsive
      to the needs of young people or when a provider was well known to the young
      woman. Their experiences underscore the need to understand the situational stress
      and sometimes difficult arrangements needed to obtain this method of
      contraception. To optimise young women's experiences of emergency contraceptive
      use, a number of strategies need to be implemented. These include improvement of
      information about emergency contraception for young women and their partners; for
      health professionals; and for the broader community. Of critical importance is
      the need to include strategies to improve access to emergency contraception. A
      number of recommendations to achieve this within current health care delivery
      sectors in Australia, as well as suggestion forfuture access are provided.

PMID- 15729809
TI  - Demonstrating outcomes in a nurse-led clinic: how primary health care nurses make
      a difference to children and their families.
AB  - The provision of primary health care to children and families is complex. The
      study outlined here explored outcomes from the provision of primary health care
      to children aged 5-13 years in a nurse-led clinic based in a primary school in
      Auckland, New Zealand. This multi-faceted study collected both qualitative and
      quantitative data, however it is the results of the quantitative arm of the study
      that are presented here. Data were collected from a variety of sources concerning
      conditions seen, age and ethnicity of users, types of services provided and
      impact on hospital usage. Findings demonstrate that the provision of
      comprehensive primary health care by the nurse at the clinic impacts positively
      on hospital visitation by children from the area where the clinic is located.

PMID- 15729810
TI  - Development of the School Entrant Health Questionnaire for assessing primary
      school children aged 5-7.
AB  - This article describes the development and pilot testing of the School Entrant
      Health Questionnaire (SEHQ) for the School Nursing Program in Victoria, Australia
      to provide a health profile of primary school children. Items likely to
      discriminate between healthy children and children having health concerns were
      generated. Domains included were: general health, medications, immunizations,
      dental health, speech/language, hearing, vision, disabilities, general
      development, behavior and emotional wellbeing, and family stress. Testing to
      determine reliability, validity and discriminability was conducted in four
      phases. The SEHQ was found to have sound reliability and good discriminability
      between students who had problems and those who did not. Analysis of the SEHQ
      data leads directly to clinical nursing actions for children identfied as having
      problems in any of the 11 domains. SEHQ is used to reach almost an Australian
      state population of 5-7year olds annually, generating a significant data base on
      this age group.

PMID- 15729811
TI  - Volunteerism: 'community mothers' in action.
AB  - Volunteers represent a growing, but often undervalued, section of service
      delivery in many areas in the community, particularly in health care. This paper
      is centred on volunteers' perceptions and experiences of home visiting gained
      through the implementation of the Community Mothers (CM) program in Western
      Australia (WA). Further, the paper aims to inform debate about the issue of
      professional versus non-professional home visitors and offers a perspective on
      the issue that may provide direction for policy makers and practitioners. This
      qualitative study involved individual telephone interviews with a volunteer
      sample of 12 participants, purposefully selected. Transcription data from each
      interview were examined and coded utilising an adapted method of content analysis
      described by Burnard (1991). Three main themes emerged in the findings as to why
      volunteers became involved in the Community Mothers Program: (1) Empathetic
      concern; (2) Contribution to community life; and (3) Lifecourse issues and
      personal development. With experiences of volunteers in home visiting, four main
      themes reflected the participants' views: (1) Facilitating client empowerment;
      (2) Facilitating personal empowerment; (3) Promoting social connectedness; and
      (4) Enabling goal setting. Although programs such as the Community Mothers
      Program aim to benefit and support mothers in the parenting role it is clear that
      there are benefits that emerge also for the individual volunteer, such as
      increased self-esteem, self-efficacy and satisfaction. Hence, measuring the
      overall outcomes that result from such program remains a major challenge.

PMID- 15729812
TI  - Current state of knowledge on child-to-mother violence: a literature review.
AB  - Child-to-mother violence is a common aspect of family violence, and presents
      nurses and health workers with continuing challenges. Though noted in the
      literature as early as the 1950's, this phenomenon remains poorly understood. A
      number of reasons for the lack of research scrutiny are proposed, the most
      compelling being that child-to-mother violence has been framed within the
      discourse of juvenile delinquency rather than family violence. Thus, unlike other
      forms of family violence, it has escaped close examination by health and welfare
      workers. A literature review was conducted to examine current knowledge of child
      to-mother violence. Study of the literature reveals only partial understandings
      of this neglected aspect of family pathology. Directions for research to address
      these gaps in knowledge are drawn from the findings of this literature review.

PMID- 15729813
TI  - Using a strengths approach to understand resilience and build health capacity in
      families.

PMID- 15729814
TI  - Determination of organotin compounds in-water by headspace solid phase
      microextraction with gas chromatography-mass spectrometry.
AB  - This investigation evaluates headspace solid-phase microextraction (HS-SPME)
      coupled with gas chromatography-mass spectrometry (GC-MS) to determine trace
      levels of organotins in water. The organotins were derivatized in situ with
      sodium tetraethylborate and adsorbed on a poly(dimethysiloxane) (PDMS)-coated
      fused silica fiber. The SPME experimental procedures to extract organotins in
      water were at pH 5, with extraction and derivatization simultaneously at 45
      degrees C for 30 min in a 2% sodium tetraethylborate solution and a sample
      solution volume in the ratio of 1:1, and desorption in the splitless injection
      port of the GC at 260 degrees C for 2 min. Detection limits are determined to be
      in the low ng/L range. According to the analysis, the linearity range is from 10
      to 10,000 ng/L with R.S.D. values below 12% except triphenyltin (24%). The
      proposed method was tested by analyzing surface seawater from the harbors on the
      Taiwanese coast for organotins residues. Some organotins studied were detected in
      the analyzed samples. Results of this study demonstrate the adequacy of the
      headspace SPME-GC-MS method for analyzing organotins in sea water samples.

PMID- 15729816
TI  - Application of a high-pressure electro-osmotic pump using nanometer silica in
      capillary liquid chromatography.
AB  - A novel designed electro-osmotic pump (EOP) with simple structure was assembled
      using three 20 cm x 530 microm i.d. fused-silica capillaries packed with 20 +/- 5
      nm silica grains for capillary liquid chromatography. It was found that the pump
      could generate pressures over 20 MPa and several microL/min flow rate for most of
      the liquids being delivered with the applied voltage less than 10 kV. By
      increasing the pressure, decreasing the applied voltage and the electrical
      current, the thermodynamic efficiency was about 1-4%. A practical application of
      the EOP in a 20cm x 150 microm i.d. 3 microm C18 fused-silica analytical
      capillary column demonstrated the applicability of the pump.

PMID- 15729815
TI  - Reversed-phase high-performance liquid chromatography behavior of chaotropic
      counteranions.
AB  - The retention behavior of inorganic liophilic anions in reversed-phase HPLC
      columns was studied. Usually, the addition of these ions to the mobile phase
      influences the retention of protonated basic analytes similar to the effect of
      amphiphilic ions (ion-pairing agents). The nature of this influence is the
      subject of this paper. HPLC retention of perchlorate (ClO4-), tetrafluoroborate
      (BF4-), and hexafluorophosphate (PF6-) ions was studied on six columns with
      different bonded phases including alkyl, phenyl and perfluorophenyl phases. The
      effect of the mobile phase ionic strength on the retention of liophilic ions was
      investigated. The influence of the type of organic modifier, acetonitrile and
      methanol, on the retention of inorganic ions was also studied and interpreted on
      the basis of adsorption from solutions. Semi-empirical expression is suggested
      for the description of the retention profile of studied liophilic ions versus the
      eluent composition. Significant retention of these ions is observed in
      acetonitrile-water eluents. Multilayer-type adsorption of the acetonitrile on the
      reversed-phase surface and its strong dispersive (or pi-pi) interactions with
      liophilic ions are responsible for significant retention of these ions. This
      accumulation of liophilic ions in the adsorbed layer on the surface of reversed
      phase material introduces an electrostatic component in the retention of
      protonated basic analytes.

PMID- 15729817
TI  - New hybrid polymeric liquid chromatography chiral stationary phase prepared by
      surface-initiated polymerization.
AB  - A new hybrid organic/inorganic HPLC chiral stationary phase (CSP1) has been
      synthesized by the grafting from (g-from) radical polymerization of an
      enantiopure diacryloyl derivative of trans-1,2-diaminocyclohexane in the presence
      of mesoporous, azo-activated silica particles. The new chiral stationary phase
      has been fully characterized by elemental analysis, differential scanning
      calorimetry, diffuse reflectance infrared spectroscopy, scanning electron
      microscopy, inverse size exclusion chromatography and Van Deemter analysis. CSP1
      shows improved chromatographic performances compared to its analog CSP2
      synthesized by the alternative grafting to (g-to) approach in which the azo
      initiator is kept in solution. CSP1 can successfully resolve several chemically
      diverse chiral compounds, using both organic and water-based eluents (normal
      phase, polar organic, etc.).

PMID- 15729818
TI  - Analysis of flame retardant additives in polymer fractions of waste of electric
      and electronic equipment (WEEE) by means of HPLC-UV/MS and GPC-HPLC-UV.
AB  - An HPLC-UV/MS method has been developed to identify and quantify flame retardants
      in post-consumer plastics from waste of electric and electronic equipment (WEEE).
      Atmospheric pressure chemical ionisation spectra of 15 brominated and phosphate
      based flame retardants were recorded and interpreted. The method was applied to
      detect flame retardant additives in polymer extracts obtained from pressurised
      liquid extraction of solid polymers. In addition, a screening method was
      developed for soluble styrene polymers to isolate a flame retardant fraction
      through the application of gel permeation chromatography (GPC). This fraction was
      transferred to an online-coupled HPLC column and detected by UV spectroscopy,
      which allowed a reliable qualitative and quantitative analysis of brominated
      flame retardants in the polymer solutions.

PMID- 15729819
TI  - Preparative isolation and purification of three flavonoids from the Chinese
      medicinal plant Epimedium koreamum Nakai by high-speed counter-current
      chromatography.
AB  - A preparative high-speed counter-current chromatography (HSCCC) method for
      isolation and purification of flavonoids from the Chinese medicinal plant
      Epimedium koreamum Nakai was successfully established by using chloroform
      methanol-water (4:3.5:2, v/v) as the two-phase solvent system. The method yielded
      11.4 mg of epimedokoreanoside I, 46.5 mg of icariin and 17.7 mg of icariside II
      from 200 mg of the crude sample in one-step separation with the purity of 98.2%,
      99.7% and 98.5%, respectively, as determined by high-performance liquid
      chromatography (HPLC). The structures of the flavonoids were identified by 1H NMR
      and 13C NMR.

PMID- 15729820
TI  - Screening of inhibitors for influenza A virus using high-performance affinity
      chromatography and combinatorial peptide libraries.
AB  - The affinity inhibitor of fusion peptide of influenza A virus has been studied
      using a combination of high-performance affinity chromatography (HPAC) and
      combinatorial peptide libraries. Fusion peptide (FP) (1-11) of influenza A virus
      was used as the affinity ligand and immobilized onto the poly(glycidyl
      methacrylate) (PGMA) beads. Positional scanning peptide libraries based on
      antisense peptide strategy and extended peptide libraries were designed and
      synthesized. The screening was carried out at acidic pH (5.5) in order to imitate
      the environment of virus fusion. A hendecapeptide FHRKKGRGKHK was identified to
      have a strong affinity to the FP (1-11). The dissociation constant of the complex
      of the hendecapeptide and the FP (1-11) is 3.10 x 10(-6) mol l(-1) in a
      physiological buffer condition. The polypeptide has a fairly inhibitory effect on
      three different strains of influenza A virus H1N1 subtype.

PMID- 15729821
TI  - Gradient ion-pair chromatographic method for the determination of iron N,N'
      ethylenediamine-di-(2-hydroxy-5-sulfophenylacetate) by high performance liquid
      chromatography-atmospheric pressure ionization electrospray mass spectrometry.
AB  - The most effective remedy for iron deficiency is the use of synthetic iron
      chelates, specifically chelates derived from polyaminecarboxylic acids as EDDHSA
      (N,N'-ethylenediamine-di-(2-hidroxy-5-sulfophenylacetic) acid). A gradient ion
      pair chromatographic method was developed to quantify the total amount of
      chelated iron in EDDHSA/Fe3+ fertilizers. Two mobile phases were used containing,
      respectively, 35 and 75% acetonitrile in a 0.005 M tetrabutylammonium hydroxide
      aqueous solution at pH 6.0. The stationary phase was a reverse phase C-18 column
      (150mm x 3.9mm i.d., dp = 5 microm). Two chromatographic peaks appeared and were
      identified by Electrospray Mass Spectrometry. The first peak corresponds to the
      monomer of EDDHSA/Fe3+ and the second peak has been assigned to condensation
      molecules. Quality parameters indicate that the method is suitable for the
      quantification of iron chelate by EDDHSA fertilizers.

PMID- 15729822
TI  - Immobilised artificial membrane chromatography coupled with molecular probing.
      Mimetic system for studying lipid-calcium interactions in nutritional mixtures.
AB  - Immobilised artificial membrane (IAM) chromatography was utilised to study the
      interactions of usual membrane probes with grafted phosphatidylcholine silica
      support, in relation to the presence of calcium ions introduced in the mobile
      phase as they are present in nutritional mixtures. IAM acts as a mimetic membrane
      of lipid emulsion globules, a major component of nutritional mixtures. The tested
      probes were 1,6-diphenyl-1,3,5-hexatriene (DPH), 9-diethylamino-5H
      benzo[alpha]phenoxazine-5-one or nile red (NR) and 2-(p-toluidinyl)naphtalene-6
      sulfonate (TNS). For each probe, partition coefficients and thermodynamic
      parameters of transfer from the mobile phase to the IAM stationary phase have
      been measured. Our results suggested that the interactions of neutral probes
      (i.e. DPH and NR) with phosphatidylcholine are driven by hydrophobic forces.
      Addition of calcium chloride to the mobile phase slightly decreased the retention
      of these neutral probes and dramatically increased that of anionic TNS. Moreover,
      an enthalpy-entropy compensation study revealed that the mechanism of interaction
      between TNS and IAM is independent of the calcium concentration. Results argued
      for the existence of electrostatic repulsion forces exerted by IAM phase towards
      anionic TNS. Addition of calcium ions into the mobile phase led to the
      establishment of an ionic double layer at the zwitterionic stationary phase
      surface weakening the electrostatic barrier and increasing TNS retention.
      Consequently, it was demonstrated that IAM appears as a suitable model to get a
      better insight on the lipid-calcium interactions taking place in nutritional
      mixtures.

PMID- 15729823
TI  - Normal phase high performance liquid chromatography for determination of
      paclitaxel incorporated in a lipophilic polymer matrix.
AB  - A normal phase (NP) high performance liquid chromatography (HPLC) method was
      developed for analysis of paclitaxel incorporated in poly(sebacic-co-ricinoleic
      acid), a lipophilic polymer matrix utilized for preparation of an injectable
      formulation for the localized delivery of paclitaxel. Thin layer chromatography
      experiments revealed that separation of paclitaxel from the polymer is dependent
      on the eluting strength (solvent strength) of the mobile phase. The HPLC system
      consists of a Purospher STRAR Si analytical HPLC column (5 microm, 250mm x 4mm,
      Merck), and 1-2.5% (v/v) methanol in dichloromethane as the mobile phase.
      Detection was by UV absorbance at 240 and 254 nm. The effect of the mobile phase
      composition on paclitaxel retention, peak shape and column efficiency, and the
      influence of the sample loading on the shape of the paclitaxel peak were studied.
      The mobile phases used for the chromatography consisted of 1.5% (v/v) methanol in
      dichloromethane. Paclitaxel was determined in the formulation and in the samples
      from degradation studies using UV detection at a wavelength of 254 nm. UV
      detection at 240 nm has advantages for following polymer matrix degradation
      products due to higher detector response at this wavelength. The utility of the
      proposed NP HPLC approach was demonstrated by assessment of intra- and inter
      batch content uniformity, and by the determination of paclitaxel content after 7
      and 60 days exposure of the paclitaxel-loaded polymer matrix to in vitro and in
      vivo degradation.

PMID- 15729824
TI  - Determination of odorous mixed chloro-bromoanisoles in water by solid-phase micro
      extraction and gas chromatography-mass detection.
AB  - A headspace-solid-phase micro-extraction (HS-SPME) and gas chromatography-mass
      spectrometry (GC-MS) method has been proposed for the simultaneous determination
      of odorous trihalogenated anisoles in water. Parameters affecting efficiency of
      HS-SPME procedure, such as the selection of the SPME coating, extraction time,
      temperature and ionic strength were optimized. The commercially available
      polydimethylsiloxane (PDMS 100 microm) fiber appears to be the most suitable for
      the simultaneous determination of these compounds. Run-to-run precision with
      relative standard deviations (R.S.D.s) between 5 and 15% were obtained for most
      of the compounds except for 2,5-dicloro-6-bromo-anisole, 2,3-dibromo-6
      chloroanisole, pentachloro- and pentabromoanisole (>20%). The method was linear
      over two orders of magnitude, and detection limits were compound dependent and
      ranged from 0.03 ng/L for 2,4,6-trichloroanisole to 0.25 ng/L for 2,3-dibromo-6
      chloroanisole. The HS-SPME-GC-MS procedure was tested using real samples and
      relatively good standard deviations were obtained when using p-iodoanisole as
      internal standard for quantification. This is the first time that the individual
      identification of odorous trihalogenated chloro-bromoanisoles has been reported,
      being HS-SPME-GC-MS a suitable method for simultaneous determination of these
      compounds in water at concentration levels below their odor limit of detection.

PMID- 15729825
TI  - Automated analysis of individual particles using a commercial capillary
      electrophoresis system.
AB  - Capillary electrophoretic analysis of individual submicrometer size particles has
      been previously done using custom-built instruments. Despite that these
      instruments provide an excellent signal-to-noise ratio for individual particle
      detection, they are not capable of performing automated analyses of particles.
      Here we report the use of a commercial Beckman P/ACE MDQ capillary
      electrophoresis (CE) instrument with on-column laser-induced fluorescence (LIF)
      detection for the automated analysis of individual particles. The CE instrument
      was modified with an external I/O board that allowed for faster data acquisition
      rates (e.g. 100 Hz) than those available with the standard instrument settings
      (e.g. 4 Hz). A series of eight hydrodynamic injections expected to contain 32 +/-
      6 particles, each followed by an electrophoretic separation at -300 V cm(-1) with
      data acquired at 100 Hz, showed 28 +/- 5 peaks corresponding to 31.9 particles as
      predicted by the statistical overlap theory. In contrast, a similar series of
      hydrodynamic injections followed by data acquisition at 4 Hz revealed only 8 +/-
      3 peaks suggesting that the modified system is needed for individual particle
      analysis. Comparison of electropherograms obtained at both data acquisition rates
      also indicate: (i) similar migration time ranges; (ii) lower variation in the
      fluorescence intensity of individual peaks for 100 Hz; and (iii) a better signal
      to-noise ratio for 4 Hz raw data. S/N improved for 100 Hz when data were smoothed
      with a binomial filter but did not reach the S/N values previously reported for
      post-column LIF detection. The proof-of-principle of automated analysis of
      individual particles using a commercially available CE system described here
      opens exciting possibilities for those interested in the study and analyses of
      organelles, liposomes, and nanoparticles.

PMID- 15729826
TI  - Determination of low-molecular-mass organic acids in any type of beer samples by
      coelectroosmotic capillary electrophoresis.
AB  - A separation and determination of a mixture of 19 low-molecular-mass organic
      acids usually present in beer samples was developed using coelectroosmotic
      capillary zone electrophoresis. A polycation (hexadimetrine bromide, HDB) has
      been added to the electrolyte, which dynamically coats the inner surface of the
      capillary and causes a fast anodic electroosmotic flow. The main factors
      affecting reversal of the EOF such as type of modifier and concentration and
      influence of organic solvents were studied. Three types of modifiers, two
      alkylammonium salts (cethyltrimethylammonium bromide and
      tetradecyltrimethylammonium bromide) and a polycation (HDB) were investigated.
      The composition of the running buffer results on a 25% 2-propanol, 0.001% HDB and
      50 mM sodium phosphate. The different instrumental parameters affecting the
      capillary electrophoretic separation were also optimized resulting on a -15 kV
      voltage with a hydrodynamic injection for 7 s with a UV detection at 210 nm. The
      applicability of the present method has been demonstrated for the determination
      of organic acids in different beer samples.

PMID- 15729827
TI  - On-channel base stacking in microchip capillary gel electrophoresis for high
      sensitivity DNA fragment analysis.
AB  - We evaluated a novel strategy for high-sensitivity DNA fragment analysis in a
      conventional glass double-T microfluidic chip. The microchip allows for a DNA on
      channel concentration based on base stacking (BS) with a microchip capillary gel
      electrophoretic (MCGE) separation step in a poly(vinylpyrrolidone) (PVP) sieving
      matrix. Depending if low conductivity caused a neutralization reaction between
      the hydroxide ions and the run buffer component Tris+, the stacking of DNA
      fragments were processed in the microchip. Compared to a conventional MCGE
      separation with a normal electrokinetic injection, the peak heights of 50-2650
      base pair (bp) DNA fragments on the MCGE-BS separation were increased 3.9-8.0
      fold. When we applied the MCGE-BS method to the analysis of a clinical sample of
      bovine theileria after PCR reaction, the peak height intensity of the amplified
      816-bp DNA fragment from the 18S rRNA of T. buffeli was enhanced 7.0-fold
      compared to that of the normal injection method.

PMID- 15729828
TI  - Towards gas chromatography-mass spectrometry coupling protocols for both
      identifying and quantification essential oils of Thymus capitatus Hoff et Link.
AB  - Essential oil of Thymus capitatus Hoff et Link is analysed by using four
      techniques: GC/pyrolyse/MS, GC/FID, electronic impact GC/MS (quadripole), and
      GC/MS (ion trap). Both major and trace components are analysed. The
      GC/pyrolyse/MS coupling provides reference to the exact mass compositions without
      any need of the previously purified references, neither for major or trace
      components. The comparison between this reference analysis and GC/FID shows that
      the FID response coefficients may vary by a mean 7% from one component to
      another. As it was expected, quadripole or ion trap response coefficients vary to
      a much greater extent (a mean 25%), although the two MS techniques response
      coefficients are first order consistent. We conclude that GC/MS coupling could be
      used not only as it is usual for reliable identifications, but also for a
      complete quantitative routine analysis of essential oils. Expected precision
      could be very similar to GC/FID precision provided correcting species by species
      the MS analysis by a mean value of the response coefficient measured for the MS
      70 eV electronic impact ionisation technologies. The GC/pyrolyse/MS coupling is
      proposed as a relevant tool for analysing reference samples containing trace
      natural species that could not be purified.

PMID- 15729829
TI  - 20 years after the winter smog episode 1985--the particle problem then and today.

PMID- 15729830
TI  - Health concerns regarding consumption of irradiated food.
AB  - Food irradiation is being promoted as a simple process that can be used to
      effectively and significantly reduce food-borne illnesses around the world.
      However, a thorough review of the literature reveals a paucity of adequate
      research conducted to specifically address health concerns that may directly
      result from the consumption of irradiated food. Consequently, there is
      considerable debate on the issue of health concerns from irradiated food among
      international agencies and between different nations. This report presents a
      critical review of scientific data and recommendations from different agencies
      and consumer groups. The objective of this review is to provide the scientific
      community and the general public with a balanced discussion on irradiated food
      from the viewpoint of an environmental or public health professional. As a result
      of this review, the authors conclude that current evidence does not exist to
      substantiate the support or unconditional endorsement of irradiation of food for
      consumption. In addition, consumers are entitled to their right of choice in the
      consumption of irradiated versus un-irradiated food. Different countries should
      further evaluate their local and global risks and benefits prior to developing
      and recommending national and international food irradiation policies.

PMID- 15729831
TI  - What can we learn today from the Central European smog episode of 1985 (and
      earlier episodes)?
AB  - In January 1985 an extended smog episode occurred in Central Europe. The Rhine
      Ruhr area (Western Germany) was affected for 5 days with maximum concentrations
      of 0.8 mg/m3 SO2 and 0.6 mg/m3 TSP (24h averages). Health effects were
      investigated during the smog period and a control period before and after the
      smog. Daily mortality increased by 8%, hospital admissions (for respiratory and
      cardiovascular causes, RC) by 15%, outpatients (RC) by 12% and ambulance
      transports (RC) by 28%. Patients with chronic bronchitis from the Ruhr area
      cities showed more exacerbations during the episode, and in school children from
      the Netherlands lung function was reduced. In Augsburg (Southern Germany) the
      smog episode was less severe (maximum concentrations 0.2 mg/m3 SO2 and 0.1 mg/m3
      TSP, 24 h averages). Here--by chance--the prospective MONICA study was ongoing.
      During the episode a significant increase of plasma viscosity, C-reactive protein
      and heart rate was observed in the participants. The highest ambient
      concentrations (maximum 24h average of 3.6 mg/m3 SO2) were measured in Erfurt
      (Eastern Germany). Surprisingly, no measurable increase of mortality occurred.
      This was explained by premature deaths during the period before the smog, were
      the concentrations had already been clearly above 1 mg/m3 SO2. An earlier episode
      took place in December 1962 in the Rhine-Ruhr area for 5 days with maximum
      concentrations of 5.0 mg/m3 SO2 and 2.4 mg/m3 TSP (24 h average). Daily mortality
      on average increased by 19%. In 1962 and 1985 the effects were stronger in cities
      with pollution mainly from traffic than in areas with pollution from industrial
      sources. In total, between 1962 and 1987 two major and several smaller smog
      episodes occurred in Central Europe. Patients with cardiovascular diseases were
      more severely affected than patients with respiratory diseases. Health effects
      were more strongly correlated with TSP than with SO2.

PMID- 15729832
TI  - Working memory deficiencies in adults associated with low-level lead exposure:
      implications of neuropsychological test results.
AB  - BACKGROUND: Although lead exposure has steadily decreased in the last few years,
      some lead is still used in the metal processing industry, mostly for wall paints
      and plumbing. Recent studies on children showed neurobehavioral effects of low
      level exposure, but little is known about the neurocognitive effects of lead
      concentrations in the upper reference range on adults. METHODS: The
      neuropsychological effects of lead exposure were examined in 39 adult outpatients
      at the Unit of Environmental Medicine (UEM), University Hospital, Aachen,
      Germany. All patients underwent a comprehensive medical examination, including
      psychiatric. Venous blood and urine samples were collected and tested for heavy
      metals and selenium. Since the neuropsychological examination was not expected to
      reveal any severe abnormalities, only specific attentiveness functions were
      analyzed (alertness, working memory, flexibility, intermodal comparison) since
      these areas were the likeliest to show objectifiable effects. The tests were
      conducted using a standardized computerized battery. RESULTS: Lead blood levels
      ranged from 1 to 65.6 microg/l (mean 27.4 +/- 16.2 microg/l). Although the
      neuropsychological test results of all patients were within the normal range,
      there were significant correlations between blood lead levels and the speed of
      information processing for working memory. CONCLUSIONS: The results indicate
      working memory dysfunctions in adults, the severity of which correlates directly
      with blood lead levels, supporting the hypothesis that increased blood lead
      levels can also be associated with measurable neurocognitive abnormalities.

PMID- 15729833
TI  - Determination of haemoglobin adducts of acrylamide and glycidamide in smoking and
      non-smoking persons of the general population.
AB  - Acrylamide (AA) is a food-borne toxicant suspected to be carcinogenic to humans.
      It is formed in the heating process of starch-containing food. Currently, there
      is a great discussion about the possible human health risks connected with the
      dietary uptake of acrylamide. Haemoglobin adducts of acrylamide and its oxidative
      metabolite glycidamide are both markers of biochemical effect. However, because
      glycidamide has a higher carcinogenic potency than acrylamide itself, the
      glycidamide adduct might mirror the genotoxicity better than acrylamide adducts.
      In order to gain more information about the human metabolism of acrylamide, we
      investigated a small group of persons for the effective internal doses of
      acrylamide and glycidamide using haemoglobin adducts as parameters of biochemical
      effect. The collective was subdivided into non-smokers (n=13) and smokers (n=16)
      by determining the smoking-specific acrylonitrile haemoglobin adduct (N
      cyanoethylvaline, CEV). The mean values for the adducts of acrylamide (N-2
      carbamoylethylvaline, AAVal) and glycidamide (N-(R,S)-2-hydroxy-2
      carbamoylethylvaline, GAVal) in nonsmokers was 19 pmol/g globin AAVal (range 7-31
      pmol/g globin) and 17 pmol/g globin GAVal (range 9-23 pmol/g globin). For smokers
      mean levels of AAVal were 80 pmol/g globin (range: 25-199 pmol/g globin) and
      those of GAVal were 53 pmol/g globin (range: 22-119 pmol/g globin). Metabolism to
      glycidamide turned out to be significantly more effective in non-smokers than in
      the higher exposed smokers. Compared with studies in rats, the metabolic
      conversion of acrylamide to glycidamide as measured by haemoglobin adducts seems
      to occur to a similar extent in humans as in rats. Risk estimations on acrylamide
      based on experimental data obtained in rats obviously did not overestimate the
      cancer risk for the general population. Furthermore, our results might indicate
      that the dose-response curve for acrylamide is not linear. This would be in line
      with the results of animal experiments on rodents.

PMID- 15729834
TI  - The Aral Sea disaster--human biomonitoring of Hg, As, HCB, DDE, and PCBs in
      children living in Aralsk-and Akchi, Kazakhstan.
AB  - Mercury and arsenic have been measured in urine samples and HCB, DDE and PCBs in
      blood samples of children from Aralsk and Akchi, Kazakhstan. Due to the special
      situation of Aralsk in the desert left by the drying out Aral Sea, environmental
      pollution with heavy metals and organic contaminants is believed to be higher
      than elsewhere in Kazakhstan. Aralsk was formerly located at the shore of the
      Aral Sea and is now far away from it. Akchi is a similar village and was included
      in this study as a Kazakh reference site. Urine concentrations of arsenic were
      higher in Akchi (9.4 microg/l) than in Aralsk (5.5 microg/l) and compared to
      children from Mannheim, Germany (4.25 microg/l; Median values). Regarding Hg,
      differences between children of Aralsk and Akchi were not significant and
      concentrations were lower than reference values from Germany. DDE contamination
      of children from Aralsk (2.48 microg/l) was significantly higher compared to
      Akchi (1.35 microg/l). DDE concentrations in blood samples from children in both
      cities were also significantly higher than the German reference value (0.7
      microg/l). HCB and PCBs levels differed significantly between both Kazakh groups.
      However, concentrations of these compounds were lower than German reference
      values and there was no significant difference to samples from Mannheim children.

PMID- 15729835
TI  - Erythropoietic changes in rats after 2.45 GJz nonthermal irradiation.
AB  - The purpose of this study was to observe the erythropoietic changes in rats
      subchronically exposed to radiofrequency microwave (RF/MW) irradiation at
      nonthermal level. Adult male Wistar rats (N=40) were exposed to 2.45 GHz
      continuous RF/MW fields for 2 hours daily, 7 days a week, at 5-10 mW/cm2. Exposed
      animals were divided into four subgroups (n=10 animals in each subgroup) in order
      to be irradiated for 2, 8, 15 and 30 days. Animals were sacrified on the final
      irradiation day of each treated subgroup. Unexposed rats were used as control
      (N=24). Six animals were included into the each control subgroup. Bone marrow
      smears were examined to determine absolute counts of anuclear cells and
      erythropoietic precursor cells. The absolute erythrocyte count, haemoglobin and
      haematocrit values were observed in the peripheral blood by an automatic cell
      counter. The bone marrow cytogenetic analysis was accomplished by micronucleus
      (MN) tests. In the exposed animals erythrocyte count, haemoglobin and haematocrit
      were increased in peripheral blood on irradiation days 8 and 15. Concurrently,
      anuclear cells and erythropoietic precursor cells were significantly decreased (p
      < 0.05) in the bone marrow on day 15, but micronucleated cells' frequency was
      increased. In the applied experimental condition, RF/MW radiation might cause
      disturbance in red cell maturation and proliferation, and induce micronucleus
      formation in erythropoietic cells.

PMID- 15729836
TI  - Spatial analysis of childhood leukemia in a case/control study.
AB  - A simple and direct analysis of the spatial distribution of childhood leukemia
      was performed using geographic data from a large case/control study. The data
      consist of cases of childhood leukemia and their corresponding birth cohort
      controls located in seven San Francisco Bay Area counties. Both parametric and
      randomization analyses show no evidence of a non-random spatial pattern of
      childhood leukemia among six of these counties. The data from San Francisco
      County, however, produce a moderately small significance probability (0.08)
      arising from a distance analysis and a significant p-value (0.01) arising from a
      frequency analysis of concordant case pairs. Although these p-values accurately
      reflect the probability of the observed spatial pattern occurring by chance
      alone, these results are based on only four cases of leukemia.

PMID- 15729837
TI  - Communication problems with environment-related health disorders as illustrated
      by a multiple chemical sensitivity (MCS) chatroom.
AB  - The problem of communication in treating multiple chemical sensitivity (MCS) was
      analysed and evaluated using the documentation of an MCS chatroom which was set
      up in April 2001 following the TV programme Gesundheitsmagazin Praxis (Health
      Magazine: Practice). Approaches were developed for solving communication problems
      in the chatroom. A total of 490 cases were evaluated, most of which (355) were
      directly or indirectly affected, 76 came from self-help groups and 10 were from 4
      guest experts invited by ZDF (Zweites Deutsches Fernsehen, Second German TV
      channel). Of these 4 experts, 2 were environmental medicine specialists, 1
      psychosomatics expert and 1 psychiatrist. Fourty-nine of the cases included a
      petition for chatroom participants to join a class-action law. Aside from
      exchanging basic information on MCS, frequent topics of discussion on the air
      were the assessment of physicians, clinics, self-help groups and experts. The
      participants also expressed their views on problems with society, politics, the
      economy, science and social security. Another common topic was communication in
      the chatroom itself, which for the most part consisted of sarcasm and insults,
      which were cause for conflicts in the chatroom. These communication problems led
      to the conclusion that a chatroom is not the best medium for discussing MCS. If a
      chatroom is to be used profitably to this end, it is imperative to have a well
      defined organisational framework which allows the exchange of current,
      scientifically accurate information while keeping discussions from escalating and
      degenerating into arguments.

PMID- 15729838
TI  - Pathways of trihalomethane uptake in swimming pools.
AB  - Chlorination of pool water leads to the formation of numerous disinfection by
      products (DBPs), chloroform usually being most abundant. Bathers and pool
      guardians take up various amounts of DBPs by different pathways. Identification
      of different uptake paths is important in order to develop a technical strategy
      for swimming pool water treatment and to develop focussed technical solutions to
      minimize THM uptake. Basically, trihalomethanes (THMs) can be taken up by
      inhalation, by dermal absorption, or orally (swallowing of water). In our
      experimental study involving up to 17 participants we quantified the body burden
      resulting from exposure to three different concentrations of chloroform in water
      and air of an indoor swimming pool, during a 60 min exercising period. Chloroform
      concentration of the water was 20.7, 7.1, and 24.8 microg/l and was not
      influenced artificially. Corresponding air CHCl3 concentrations were measured at
      two different levels (20 cm and 150 cm) and ranged from to 85 to 235 microg/m3.
      To dissociate the dermal exposure route from that of inhalation, THM
      concentrations were measured in the blood of subjects practicing in an indoor
      pool with and without scuba tanks, as well as in the blood of subjects walking
      around the pool without swimming. Chloroform concentrations were measured in
      blood samples before and after each exercise period. Blood chloroform
      concentration of participants with scuba tanks was 0.32 +/- 0.26 microg/l,
      without scuba tanks 0.99 +/- 0.47 micro/l, and for persons walking around the
      pool 0.31 +/- 0.25 microg/l. Our results indicate that THMs are mainly taken up
      over the respiratory pathway. Only about one third of the total burden is taken
      up over the skin. We examined the relationship between blood concentration and
      environmental chloroform concentrations by using linear regression models. Blood
      concentrations are correlated to air chloroform concentrations; correlation to
      water concentrations is less obvious.

PMID- 15729839
TI  - Isolation of Escherichia coli O157 from human and bovine faeces in the Urbino
      area, Italy.
AB  - We examined 476 faecal samples from subjects aged from 0 to >60 years, 283 with
      diarrhoea and 193 with illnesses involving other sites or clinically healthy, and
      154 samples of faeces of healthy cattle, in order to define the diffusion of E.
      coli O157 in the Urbino area. The samples were seeded by both direct streaking
      onto cefixime tellurite sorbitol Mac Conkey agar (CT-SMAC) and previous
      enrichment in cefixime tellurite tryptone soya broth for human specimens and in
      cefixime vancomicin tryptone soya broth for bovine samples. The strains of E.
      coli O157 were characterized by verocytotoxin and adhesin eae genes detection. We
      isolated one strain of E. coli O157 (0.2%) from a man 68 year old who had bloody
      diarrhoea, and one strain (0.64%) from a weaned calf. Both isolates carried the
      adhesin eae gene, but only the bovine strain was VT2+. The study shows a low
      diffusion of E. coli O157 in the Urbino area, confirming the epidemiological data
      on the national territory.

PMID- 15729840
TI  - Prevalence of Pseudomonas aeruginosa in households of patients with cystic
      fibrosis.
AB  - Colonization of airways with Pseudomonas aeruginosa (PA) is known to be a risk
      factor for infection and adverse clinical outcome in patients with cystic
      fibrosis (CF). Whereas infections with PA have been linked to contaminated
      medical devices in hospitals, sources of colonization and infection with PA in
      households of patients with CF remain to be identified. Using a standardized
      sampling protocol, we prospectively examined the presence of PA in 102 households
      of patients with CF in Germany. PA was detected in 73 (71.6%) of 102 households.
      PA was detected most frequently in drains of showers (39.6%), drainpipes of hand
      basins in kitchens (35.0%) and bathrooms (34.7%), and drainpipes of toilets
      (26.5%). Toilet seats and dish-clothes did not show PA in any household. The
      frequency and intensity of cleaning measures did not impact the detection rate of
      PA. Results of the present study for the first time determinate the rate of
      contamination with PA in households of patients with CF. Future studies will
      determine the risk of transmission of PA from households locations to patients
      with CF.

PMID- 15729841
TI  - Comparison of commercially available media for the recovery of Legionella
      species.
AB  - A lack of standardization of environmental monitoring techniques for Legionella
      spp. complicates the interpretation and comparison of results from different
      institutions. Since the quality of the culture media has enormous effect on the
      recovery of Legionella spp. a comparative assessment of commercially available
      media from four manufactures (Becton Dickenson, BioMerieux, Heipha, and Oxoid)
      was performed. For this, samples containing infected Acanthamoeba castellanii
      cells, samples from the External Quality Assurance Scheme (EQA) run by the Health
      Protection Agency in London and water samples from a hospital in Dresden,
      Germany, were investigated. The glycine-containing media (GVPC) from four
      manufactures were equally effective in growing legionellae. However, this medium
      formulation inhibited some of the non-pneumophila strains tested which was not
      observed with the selective BMPA and non-selective BCYE-agar.

PMID- 15729842
TI  - Student health policy of a German medical school--results of a cross sectional
      study concerning students' immunity to vaccine-preventable diseases.
AB  - Medical students come into contact with infectious materials early in their
      medical education. Aim of this study was to assess medical students' immunity to
      vaccine-preventable diseases and to ensure immunity against hepatitis B. An
      occupational health medical was offered to all medical students with special
      emphasis on preclinical students. The examination included a check of the
      certificates of vaccination and serological tests concerning hepatitis B virus,
      hepatitis C virus and, on request, HIV. A lecture on occupational risks and
      general precautions was given to the students. In 7 of 804 tested students
      serological markers of a previous hepatitis B infection were discovered,
      fortunately none of the students was infectious. No case of infection with the
      hepatitis C virus (n=804) or HIV (n=700 tested voluntary) was identified. For 52
      percent of the students vaccination against hepatitis B was necessary to
      guarantee protective immunity. Documented protection against other vaccine
      preventable diseases as tetanus (71%), diphtheria (67%), poliomyelitis (56%),
      pertussis (2%), measles (32%), mumps (24%) and rubella (25%) was also
      insufficient. As a result a vaccination against hepatitis B in childhood without
      documented response doesn't guarantee a sufficient protection. An occupational
      health medical at the beginning of preclinical training seems to be an adequate
      method of making medical students aware of occupational risks, immunization
      policies and the importance of occupational medicine.

PMID- 15729843
TI  - Analysis of microcystins in freshwater samples using high performance liquid
      chromatography and an enzyme-linked immunosorbent assay.
AB  - Blooms of non-toxin producing and toxin producing cyanobacteria are often
      observed in lakes, reservoirs and slowly flowing eutrophic freshwater.
      Microcystin congeners are the most important group of cyanobacterial toxins and
      determination of the microcystin concentration is necessary in order to assess
      the health risk when such waters are used for recreational purposes. The most
      widely used standard method for analysis of microcystins is high-performance
      liquid chromatography (HPLC). But this technique is time-consuming and needs a
      special expensive equipement. Therefore a commercially available microcystin
      enzyme-linked immunosorbent assay (ELISA) could be an alternative. However, when
      performed as recommended by the manufacturer, the ELISA is not suitable for a
      valid quantitative analysis. We have therefore modified the microcystin
      extraction method and the ELISA protocol and have been able to use the ELISA for
      a quantitative analysis comparable to that of the widely recommended HPLC method.
      The modified ELISA provides a relatively simple and highly sensitive approach for
      the quantitative analysis of microcystins in freshwater. Results can be obtained
      within two to three days after sampling.

PMID- 15729844
TI  - Turning up the heat on infection control--APIC's 31st Annual Educational
      Conference and International Meeting 2004.
AB  - Infection prevention and control is facing new challenges worldwide: emerging and
      reemerging infectious diseases, increasing resistance of bacterial pathogens,
      virtually unlimited possibilities of germ transmission due to travel activities,
      and the necessity to improve emergency and bioterrorism response capabilities. In
      a way it is designative that the Association of Professionals in Infection
      Control (APIC) met in Phoenix, the name of which is symbolic of rebirth.
      Accordingly the conference covered a wide spectrum of infection control-related
      topics and new aspects thereof. Recognized speakers provided an insight into
      basic principles and latest updates on several infectious diseases, detection and
      prevention strategies, patient safety as well as professional development, to
      name just a few. Networking was the magic word of the event, and all participants
      were successfully encouraged to start right away with it.

PMID- 15729845
TI  - An automated PLS search for biologically relevant QSAR descriptors.
AB  - An automated PLS engine, WB-PLS, was applied to 1632 QSAR series with at least 25
      compounds per series extracted from WOMBAT (WOrld of Molecular BioAcTivity). WB
      PLS extracts a single Y variable per series, as well as pre-computed X variables
      from a table. The table contained 2D descriptors, the drug-like MDL 320 keys as
      implemented in the Mesa A&C Fingerprint module, and in-house generated
      topological-pharmacophore SMARTS counts and fingerprints. Each descriptor type
      was treated as a block, with or without scaling. Cross-validation, variable
      importance on projections (VIP) above 0.8 and q2 > or = 0.3 were applied for
      model significance. Among cross-validation methods, leave-one-in-seven-out (CV7)
      is a better measure of model significance, compared to leave-one-out (measuring
      redundancy) and leave-half-out (too restrictive). SMARTS counts overlap with 2D
      descriptors (having a more quantitative nature), whereas MDL keys overlap with in
      house fingerprints (both are more qualitative). The SMARTS counts is the most
      effective descriptor system, when compared to the other three. At the individual
      level, size-related descriptors and topological indices (in the 2D property
      space), and branched SMARTS, aromatic and ring atom types and halogens are found
      to be most relevant according to the VIP criterion.

PMID- 15729846
TI  - Variable selection and model validation of 2D and 3D molecular descriptors.
AB  - We have found that molecular shape and electrostatics, in conjunction with 2D
      structural fingerprints, are important variables in discriminating classes of
      active and inactive compounds. The subject of this paper is how to explore the
      selection of these variables and identify their relative importance in
      quantitative structure-activity relationships (QSAR) analysis. We show the use of
      these variables in a form of similarity searching with respect to a crystal
      structure of a known bound ligand. This analysis is then validated through k-fold
      cross-validation of enrichments via several common classifiers. Additionally, we
      show an effective methodology using the variables in hypothesis generation;
      namely, when the crystal structure of a bound ligand is not known.

PMID- 15729847
TI  - Locally linear embedding for dimensionality reduction in QSAR.
AB  - Current practice in Quantitative Structure Activity Relationship (QSAR) methods
      usually involves generating a great number of chemical descriptors and then
      cutting them back with variable selection techniques. Variable selection is an
      effective method to reduce the dimensionality but may discard some valuable
      information. This paper introduces Locally Linear Embedding (LLE), a local non
      linear dimensionality reduction technique, that can statistically discover a low
      dimensional representation of the chemical data. LLE is shown to create more
      stable representations than other non-linear dimensionality reduction algorithms,
      and to be capable of capturing non-linearity in chemical data.

PMID- 15729848
TI  - Genetic algorithms and self-organizing maps: a powerful combination for modeling
      complex QSAR and QSPR problems.
AB  - Modeling non-linear descriptor-target activity/property relationships with many
      dependent descriptors has been a long-standing challenge in the design of
      biologically active molecules. In an effort to address this problem, we couple
      the supervised self-organizing map with the genetic algorithm. Although self
      organizing maps are non-linear and topology-preserving techniques that hold great
      potential for modeling and decoding relationships, the large number of
      descriptors in typical quantitative structure-activity relationship or
      quantitative structure-property relationship analysis may lead to spurious
      correlation(s) and/or difficulty in the interpretation of resulting models. To
      reduce the number of descriptors to a manageable size, we chose the genetic
      algorithm for descriptor selection because of its flexibility and efficiency in
      solving complex problems. Feasibility studies were conducted using six different
      datasets, of moderate-to-large size and moderate-to-great diversity; each with a
      different biological endpoint. Since favorable training set statistics do not
      necessarily indicate a highly predictive model, the quality of all models was
      confirmed by withholding a portion of each dataset for external validation. We
      also address the variability introduced onto modeling through dataset
      partitioning and through the stochastic nature of the combined genetic algorithm
      supervised self-organizing map method using the z-score and other tests.
      Experiments show that the combined method provides comparable accuracy to the
      supervised self-organizing map alone, but using significantly fewer descriptors
      in the models generated. We observed consistently better results than partial
      least squares models. We conclude that the combination of genetic algorithms with
      the supervised self-organizing map shows great potential as a quantitative
      structure-activity/property relationship modeling tool.

PMID- 15729850
TI  - Comparison of commercially available genetic algorithms: gas as variable
      selection tool.
AB  - Many commercially available software programs claim similar efficiency and
      accuracy as variable selection tools. Genetic algorithms are commonly used
      variable selection methods where most relevant variables can be differentiated
      from 'less important' variables using evolutionary computing techniques. However,
      different vendors offer several algorithms, and the puzzling question is: which
      one is the appropriate method of choice? In this study, several genetic algorithm
      tools (e.g. GFA from Cerius2, QuaSAR-Evolution from MOE and Partek's genetic
      algorithm) were compared. Stepwise multiple linear regression models were
      generated using the most relevant variables identified by the above genetic
      algorithms. This procedure led to the successful generation of Quantitative
      Structure activity Relationship (QSAR) models for (a) proprietary datasets and
      (b) the Selwood dataset.

PMID- 15729849
TI  - Variable selection and specification of robust QSAR models from multicollinear
      data: arylpiperazinyl derivatives with affinity and selectivity for alpha2
      adrenoceptors.
AB  - Two QSAR models have been identified that predict the affinity and selectivity of
      arylpiperazinyl derivatives for alpha1 and alpha2 adrenoceptors (ARs). The models
      have been specified and validated using 108 compounds whose structures and
      inhibition constants (Ki) are available in the literature [Barbaro et al., J.
      Med. Chem., 44 (2001) 2118; Betti et al., J. Med. Chem., 45 (2002) 3603; Barbaro
      et al., Bioorg. Med. Chem., 10 (2002) 361; Betti et al., J. Med. Chem., 46 (2003)
      3555]. One hundred and forty-seven predictors have been calculated using the
      Cerius 2 software available from Accelrys. This set of variables exhibited
      redundancy and severe multicollinearity, which had to be identified and removed
      as appropriate in order to obtain robust regression models free of inflated
      errors for the beta estimates - so-called bouncing betas. Those predictors that
      contained information relevant to the alpha2 response were identified on the
      basis of their pairwise linear correlations with affinity (-log Ki) for alpha2
      adrenoceptors; the remaining variables were discarded. Subsequent variable
      selection made use of Factor Analysis (FA) and Unsupervised Variable Selection
      (UzFS). The data was divided into test and training sets using cluster analysis.
      These two sets were characterised by similar and consistent distributions of
      compounds in a high dimensional, but relevant predictor space. Multiple
      regression was then used to determine a subset of predictors from which to
      determine QSAR models for affinity to alpha2-ARs. Two multivariate procedures,
      Continuum Regression (the Portsmouth formulation) and Canonical Correlation
      Analysis (CCA), have been used to specify models for affinity and selectivity,
      respectively. Reasonable predictions were obtained using these in silico
      screening tools.

PMID- 15729851
TI  - Descriptors you can count on? Normalized and filtered pharmacophore descriptors
      for virtual screening.
AB  - The three-dimensional (3D) binary pharmacophore fingerprints find wide
      application as descriptors in applications ranging from virtual screening through
      library design. While the 3D content they capture is an intuitively attractive
      feature of such measures, maximizing their signal to noise ratio has proven to be
      a tricky balancing act. This issue surfaces primarily due to the potential of
      such fingerprints to create an explosion of pharmacophores as molecular
      complexity and flexibility increases. In this article, we describe a modification
      to the fingerprint generation process that normalizes pharmacophore occurrence
      frequency by the conformational ensemble size used to derive the descriptor. By
      including pharmacophore frequency and conformational count, the importance of a
      given pharmacophore is weighted by the probability of its existence within a
      given conformational ensemble, rather than treating each pharmacophore equally.
      In addition, a number of filters have been added to permit the removal of
      unwanted pharmacophores from the descriptor set. These filters are based on
      pharmacophore composition (e.g. permutations made up primarily of lipophilic
      and/or aromatic centers), and size (pharmacophore perimeter length relative to
      the largest perimeter length found in the molecule). The highly uneven nature of
      pharmacophore distributions across the conformational ensemble used to generate
      them is highlighted, as are enrichment comparisons with their binary fingerprint
      peers. In addition, the limitations in descriptor comparison validation are high
      lighted as an illustration of the need for more extensive validation experiments.

PMID- 15729852
TI  - Measuring CAMD technique performance: a virtual screening case study in the
      design of validation experiments.
AB  - The dynamic nature and comparatively young age of computational chemistry is such
      that novel algorithms continue to be developed at a rapid pace. Such efforts are
      often wrought at the expense of extensive experimental validations of said
      techniques, preventing a deeper understanding of their potential utility and
      limitations. Here we address this issue for ligand-based virtual screening
      descriptors through design of validation experiments that better reflect the aims
      of real world application. Applying the newly defined chemotype enrichment
      approach, a variety of two- and three-dimensional (2D/3D) similarity descriptors
      have been compared extensively across data sets from four diverse target types.
      The inhibitors within said data sets contain molecules exhibiting a wide array of
      substructure functionality, size and flexibility, permitting descriptor
      comparison in myriad settings. Relative descriptor performance under these
      conditions is examined, including results obtained using more typical virtual
      screening validation experiments. Guidelines for optimal application of said
      descriptors are also discussed in the context of the results obtained, as is the
      potential utility of fingerprint filtering.

PMID- 15729853
TI  - QSAR modeling based on the bias/variance compromise: a harmonious and
      parsimonious approach.
AB  - Modeling quantitative structure-activity relationships (QSAR) is considered with
      an emphasis on prediction. An abundance of methods are available to develop such
      models. Using a harmonious approach that balances the bias and variance of
      predictions, the best calibration models are identified relative to the bias and
      variance criteria used. Criteria utilized to determine the adequacy of models are
      the root mean square error of calibration (RMSEC) and validation (RMSEV),
      respective R2 values, and the norm of the regression vector. QSAR data from the
      literature are used to demonstrate concepts. For these data sets and criteria
      used, it is suggested that models obtained by ridge regression (RR) are more
      harmonious and parsimonious than models obtained by partial least squares (PLS)
      and principal component regression (PCR) when the data is mean-centered. The most
      harmonious RR models have the best bias/variance tradeoff, reflected by the
      smallest RMSEC, RMSEV, and regression vector norms and the largest calibration
      and validation R2 values. The most parsimonious RR models have the smallest
      effective rank.

PMID- 15729854
TI  - Validation tools for variable subset regression.
AB  - Variable selection is applied frequently in QSAR research. Since the selection
      process influences the characteristics of the finally chosen model, thorough
      validation of the selection technique is very important. Here, a validation
      protocol is presented briefly and two of the tools which are part of this
      protocol are introduced in more detail. The first tool, which is based on
      permutation testing, allows to assess the inflation of internal figures of merit
      (such as the cross-validated prediction error). The other tool, based on noise
      addition, can be used to determine the complexity and with it the stability of
      models generated by variable selection. The obtained statistical information is
      important in deciding whether or not to trust the predictive abilities of a
      specific model. The graphical output of the validation tools is easily accessible
      and provides a reliable impression of model performance. Among others, the tools
      were employed to study the influence of leave-one-out and leave-multiple-out
      cross-validation on model characteristics. Here, it was confirmed that leave
      multiple-out cross-validation yields more stable models. To study the performance
      of the entire validation protocol, it was applied to eight different QSAR data
      sets with default settings. In all cases internal and external model performance
      was good, indicating that the protocol serves its purpose quite well.

PMID- 15729855
TI  - Statistical variation in progressive scrambling.
AB  - The two methods most often used to evaluate the robustness and predictivity of
      partial least squares (PLS) models are cross-validation and response
      randomization. Both methods may be overly optimistic for data sets that contain
      redundant observations, however. The kinds of perturbation analysis widely used
      for evaluating model stability in the context of ordinary least squares
      regression are only applicable when the descriptors are independent of each other
      and errors are independent and normally distributed; neither assumption holds for
      QSAR in general and for PLS in particular. Progressive scrambling is a novel,
      nonparametric approach to perturbing models in the response space in a way that
      does not disturb the underlying covariance structure of the data. Here, we
      introduce adjustments for two of the characteristic values produced by a
      progressive scrambling analysis - the deprecated predictivity (Q*2s) and standard
      error of prediction (SDEPs*) - that correct for the effect of introduced
      perturbation. We also explore the statistical behavior of the adjusted values
      (Q*2(0) and SDEP0*) and the sensitivity to perturbation (dq2/dryy'2). It is shown
      that the three statistics are all robust for stable PLS models, in terms of the
      stochastic component of their determination and of their variation due to
      sampling effects involved in training set selection.

PMID- 15729856
TI  - Classification of a large anticancer data set by adaptive fuzzy partition.
AB  - An Adaptive Fuzzy Partition (AFP) algorithm, derived from Fuzzy Logic concepts,
      was used to classify an anticancer data set, including about 1300 compounds
      subdivided into eight mechanisms of action. AFP classification builds
      relationships between molecular descriptors and bio-activities by dynamically
      dividing the descriptor hyperspace into a set of fuzzy subspaces. These subspaces
      are described by simple linguistic rules, from which scores ranging between 0 and
      1 can be derived. The latter values define, for each compound, the degrees of
      membership of the different mechanisms analyzed. A particular attention was
      devoted to develop structure-activity relations that have a real utility. Then,
      well-defined and widely accepted protocols were used to validate the models by
      defining their robustness and prediction ability. More particularly, after
      selecting the most relevant descriptors with help of a genetic algorithm, a
      training set of 640 compounds was isolated by a rational procedure based on Self
      Organizing Maps. The related AFP model was then validated with help of a
      validation set and, above all, of cross-validation and Y-randomization
      procedures. Good validation scores of about 80% were obtained, underlining the
      robustness of the model. Moreover, the prediction ability was evaluated with 374
      test compounds that had not been used to establish the model and 77% of them were
      predicted correctly.

PMID- 15729857
TI  - 3D-QSAR illusions.
AB  - 3D-QSAR is typically used to construct models (1) to predict activities, (2) to
      illustrate significant regions, and (3) to provide insight into possible
      interactions. To the contrary, examples are described herein which make it clear
      that the predictivity of such models remains elusive, that so-called significant
      regions are subject to the vagaries of alignment, and that the nature of possible
      interactions heavily depends on the eye of the beholder. Although great strides
      have been made in the imaginative use of 3D-descriptors, 3D-QSAR remains largely
      a retrospective analytical tool. The arbitrary nature of both the alignment
      paradigm and atom description lends itself to capricious models, which in turn
      can lead to distorted conclusions. Despite these illusionary pitfalls,
      predictions can be enhanced when the test set is bounded by the descriptor space
      represented in the training set. Interpretation of significant interaction
      regions becomes more meaningful when alignment is constrained by a binding site.
      Correlations obtained with a variety of atom descriptors suggest choosing useful
      ones, in particular, in guiding synthetic effort.

PMID- 15729859
TI  - Oxidative stress-mediated skin damage in an experimental mobile phone model can
      be prevented by melatonin.
AB  - Most mobile phones emit 900 MHz of radiation that is mainly absorbed by the
      external organs. The effects of 900 MHz of radiation on fibrosis, lipid
      peroxidation, and anti-oxidant enzymes and the ameliorating effects of melatonin
      (Mel) were evaluated in rat skin. Thirty Wistar-Albino rats were used in the
      study. The experimental groups were the control group, the irradiated group (IR),
      and the irradiated+Mel treated group (IR+Mel). A dose of 900 MHz, 2 W radiation
      was applied to the IR group every day for 10 days (30 min/day). The IR+Mel group
      received 10 mg/kg/day melatonin in tap water for 10 days before the irradiation.
      At the end of the 10th day, a skin specimen was excised from the thoracoabdominal
      area. The levels of malondialdehyde (MDA) and hydroxypyroline and the activities
      of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase
      (CAT) were studied in the skin samples. MDA and hydroxyproline levels and
      activities of CAT and GSH-Px were increased significantly in the IR group
      compared to the control group (p<0.05) and decreased significantly in the IR+Mel
      group (p<0.05). SOD activity was decreased significantly in the IR group and this
      decrease was not prevented by the Mel treatment. These results suggest that rats
      irradiated with 900 MHz suffer from increased fibrosis and lipid peroxidation
      (LPO). Mel treatment can reduce the fibrosis and LPO caused by radiation.

PMID- 15729858
TI  - Using DNA damage responses to prevent and treat skin cancers.

PMID- 15729860
TI  - A comparison of dermoscopic features among lentigo senilis/initial seborrheic
      keratosis, seborrheic keratosis, lentigo maligna and lentigo maligna melanoma on
      the face.
AB  - Clinical differentiation of facial lentigo senilis/initial seborrheic keratosis
      (LS/ISK), seborrheic keratosis (SK), lentigo maligna (LM), and lentigo maligna
      melanoma (LMM) can be difficult. Dermoscopy improves the diagnoses in pigmented
      skin lesions (PSLs), but it is not helpful for the sun-exposed face because of
      the flat rete ridges without network-derived features. Therefore, development of
      new diagnostic criteria for this particular localization is a current issue of
      dermatology. In this retrospective study, dermoscopic slides of facial pigmented
      skin lesions of 66 patients referred to two clinics in Turkey were evaluated. Our
      aim was to determine the reliability of dermoscopy in the differentiation of
      these entities. The facial PSLs of 66 patients (34 males and 32 females) (median
      age: 58.2) were photographed with a Dermaphot (Heine, Hersching, Germany) over a
      five year period from November of 1995 to May of 2000. All of the dermoscopic
      slides were analysed according to 27 dermoscopic criteria developed by Schiffner
      et al. This data set contained 22 histologically proven malignant (14 LM, 8 early
      LMM) and 44 benign (18 SK, 26 LS/ISK) PSLs. In general, asymmetric pigmented
      follicular openings, dark streaks, slate-gray streaks, dark globules, slate-gray
      globules, dark dots, dark rhomboidal structures, light brown rhomboidal
      structures, dark homogeneous areas and dark pseudonetworks were statistically
      significant for malignant growth. On the other hand, milia-like cysts,
      pseudofollicular openings, cerebriform structures, light brown globules, light
      brown dots, light brown homogeneous areas, yellow opaque homogeneous areas, and
      light brown pseudonetworks were statistically significant for benign growth. This
      research emphasizes that dermoscopic features on the face differ from criteria
      used in other locations of the body. Analysis of the data suggests that
      dermoscopy can be used in the differentiation of LS/ISK, SK, LM and LMM from each
      other.

PMID- 15729861
TI  - Taste disorders in healthy "carriers" and "non-carriers" of Candida albicans and
      in patients with candidosis of the tongue.
AB  - Impairments in taste perception may be caused by a number of factors, including
      the presence of Candida albicans in the oral cavity. We attempted to establish
      whether the presence of Candida albicans on the tongue is a cause of taste
      disorders by studying taste disorders in patients with candidosis of the tongue
      and in healthy "carriers" and "non-carriers" of C. albicans. Taste disorders and
      their severity were objectively assessed by the filter-paper disk method in 18
      patients with candidosis of the tongue and in 33 healthy "carriers" and 167
      healthy "non-carriers" of C. albicans. The gustatory function was re-tested in 7
      patients and 8 "carriers" after treatment with topical anti-mycotic medication to
      detect any improvement. Patients with candidosis of the tongue and "carriers" of
      C. albicans demonstrated significantly higher incidences (p<0.001) of taste
      disorders than did "non-carriers". The mean taste threshold of each of the four
      individual taste qualities was significantly higher in patients with candidosis
      than in "non-carriers". The average taste threshold was significantly higher in
      "carriers" than in "non-carriers". Post-treatment improvement or recovery from
      taste disorders was obtained in 5 out of 7 patients (71.4%) with candidosis and
      in 7 out of 8 "carriers" (87.5%) of C. albicans. This study clearly demonstrates
      that not only overt candidosis of the tongue but also commensal harboring of C.
      albicans is a cause of taste disorders.

PMID- 15729862
TI  - A study of leprosy reactions in a tertiary hospital in Delhi.
AB  - A retrospective study of 531 leprosy patients was undertaken to study the profile
      of reactions in the post Multi-Drug-Therapy period in a tertiary hospital in
      Delhi. BT was the most common group. The prevalence of reactions was found to be
      8.09% for the Type 1 and 4.70% for the Type 2 reactions for a male:female ratio
      of 2.2. The Type 1 reaction was most frequently observed in the BB group followed
      by BL, BT and LL groups respectively. More than half of the patients had
      reactions at the time of presentation. In only 39.8% of the patients did reaction
      follow Multi-Drug-Therapy. In 4.5% of the patients with Type 1 reactions (T1R),
      concomitant infections were noted. The most common presentation of T1R was
      cutaneous lesions (74.41%) followed by cutaneous lesions and neuritis (53.6%),
      neuritis alone (12.1%), and only edema of hands and feet (7.31%) respectively.
      The Type 2 reactions (T2R) presented chiefly as papulo-nodular (92%) lesions
      followed by pustulonecrotic (8%) lesions. Associated neuritis was found in 40%
      and periosteitis and iritis in 8% and 4%, respectively. In 8.6% of the patients
      with T2R, precipitating factors could be observed. The prevalence of deformities
      in patients with reaction was 25%, and was more common in females. Deformities
      were observed in 23.25% of the T1R patients and 28% of the T2R patients.

PMID- 15729863
TI  - Fungal melanonychia.
AB  - Melanonychia is characterized by tan, brown, or black pigmentation within the
      nail plate. Fungal melanonychia is rare and may simulate longitudinal
      melanonychia caused by melanocytic lesions. We report six cases of fungal
      melanonychia which were confirmed histopathologically or mycologically. On
      culture, Candida and/or Aspergillus species were isolated in four patients. The
      nail pigmentation improved after treatment with antifungal agents in all cases,
      but one patient experienced a new lesion on another nail after cessation of
      treatment. Fungal infection should be considered as a cause of melanonychia, and
      fungal melanonychia should be differentiated from the melanonychia caused by
      melanocytic lesions, particularly by subungual melanoma.

PMID- 15729865
TI  - Acquired reactive perforating collagenosis in a patient with lung fibrosis.
AB  - Reactive perforating collagenosis (RPC) is a rare disorder characterized by the
      transepidermal elimination of altered collagen. The inherited form of RPC begins
      in early childhood, but acquired reactive perforating collagenosis (ARPC) begins
      in adult life. ARPC is associated with diabetes mellitus, renal disease, and
      malignancy. ARPC with lung fibrosis has not previously been reported in the
      literature, and the relationship between ARPC and lung fibrosis has not been
      studied. The etiological relationship between the two disorders appears to be
      uncertain. Although their association in this case could be due to chance, it may
      be due to the transforming growth factor beta abnormalities seen in both
      diseases. In this report, we describe a case of ARPC with lung fibrosis and
      propose an etiological association between the two diseases.

PMID- 15729864
TI  - A case of rheumatoid nodulosis successfully treated with surgery.
AB  - We report the case of a 76 year-old male with multiple subcutaneous nodules, but
      without joint symptoms or deformities, who was diagnosed histopathologically with
      rheumatoid nodulosis after resection of the nodules. Rheumatoid nodulosis is a
      disease characterized by multiple subcutaneous nodules that are
      histopathologically similar to rheumatoid nodules, a high titer of rheumatoid
      factor, and radiologically detectable cystic bone lesions, but with none or few
      of the systemic manifestations orjoint activity of rheumatoid arthritis (RA). It
      is considered to be a benign variant of RA. This rare disease must be considered
      when a case of multiple subcutaneous nodules is encountered, even in aged males
      withoutjoint symptoms or deformities.

PMID- 15729866
TI  - Odontogenic sinus tract to the neck skin: a case report.
AB  - We describe a 22-year-old woman with neck skin sinus tract that developed as a
      consequence of dental infection. The patient was treated twice in an
      inappropriate way with recurrence of the sinus tract. We opted for an extraction
      of the tooth. This case illustrates the need for cooperative diagnostic referrals
      between physicians and dentists.

PMID- 15729867
TI  - Asymmetrical nonscalp aplasia cutis congenita: a case report.
AB  - Aplasia cutis congenita or congenital absence of the skin is a rare and serious
      congenital disease; its etiopathogenesis remains unclear. In this condition,
      localized or widespread areas of skin are absent at birth. A newborn suffering
      from an unusual aplasia cutis congenita located asymmetrically on the nonscalp,
      without blistering, was presented. This patient was completely healed with
      conservative treatment.

PMID- 15729869
TI  - Beta-mannosidosis with angiokeratoma corporis diffusum.
AB  - Beta-mannosidosis is a lysosomal disorder which is caused by a deficiency of beta
      mannosidase. This disorder was first described in goats. Twelve human cases have
      already been reported. We present the first case in Japan in whom the diagnosis
      was reached from angiokeratoma corporis diffusum. Futhermore, mental retardation,
      hearing loss, and renal failure were also detected. Pseudoxanthoma elasticum was
      also present, but whether it is a complication of beta-mannosidosis or not
      remains unknown. The activity level of beta-mannosidase in the patient's plasma
      was only 2% of the normal range, while that in the patient's mother was 40%. We
      suggest that beta-mannosidosis should be one of the differential diagnoses when
      lysosomal enzyme disorders are suspected in cases of angiokeratoma corporis
      diffusum.

PMID- 15729868
TI  - Human papillomavirus associated with Bowen's disease of the finger.
AB  - We report here a case of Bowen's disease that developed in the periungual area of
      the left ring finger of a 55-year-old Japanese male. Because the histology of the
      lesion mimicked in part the features of a common wart, a PCR-based analysis of
      human papillomavirus (HPV) DNA and sequencing of viral DNA of PCR-amplified
      fragments were performed. The lesion contained HPV11 and 16 DNA, and HPV was
      suspected to play a role in the development of the lesion.

PMID- 15729870
TI  - Malassezia folliculitis on the scalp of a 12-year-old healthy child.
AB  - Malassezia folliculitis is a condition chracterized by itchy follicular papules
      and pustules with erythema. Malassezia yeasts are the pathogens in this
      condition. It is mainly located on the back, shoulders, and chest. Presented here
      is a 12-year-old boy with malassezia folliculitis on the scalp. The case was
      found to be worthy of presentation because it rarely occurs in childhood and is
      rarely located on the scalp.

PMID- 15729871
TI  - Syringocystadenoma papilliferum: report of the first case on the lower leg.
AB  - Syringocystadenoma Papilliferum (SCAP) is a benign adnexal tumor which most
      frequently arises from an organoid nevus on the head and neck. Although they are
      rarely found on the trunk and limbs, we treated a case of this disorder on the
      lower leg. A 26-year-old man had an asymptomatic tumor on his lower leg.
      Histopathological examination showed it to be a typical SCAP on organoid nevus.
      This is the first report of SCAP on the lower leg.

PMID- 15729872
TI  - Angiokeratoma Fordyce of the glans penis: combined treatment with erbium: YAG and
      532 nm KTP (frequency doubled neodynium: YAG) laser.
AB  - A rare case of angiokeratoma Fordyce localized on the margin of the glans penis
      in a 52-year-old Caucasian patient is reported. Combined treatment with Erbium:
      YAG and 532 nm KTP (frequency doubled Neodynium: YAG) laser led to excellent
      cosmetic results.

PMID- 15729873
TI  - Subcorneal pustular dermatosis associated with palmo-plantar pustular psoriasis:
      response to colchicine therapy.

PMID- 15729874
TI  - A case of otomycosis caused by Aspergillus sclerotiorum.

PMID- 15729875
TI  - Topotecan induced nail pigmentation.

PMID- 15729876
TI  - [An outbreak of encephalopathy after eating autumn mushroom (Sugihiratake;
      Pleurocybella porrigens) in patients with renal failure: a clinical analysis of
      ten cases in Yamagata, Japan].
AB  - In September and October, 2004, an outbreak of encephalopathy of unknown etiology
      occurred in certain areas of Japan including Yamagata, Akita, and Niigata
      prefectures. These patients had a history of chronic renal failure, most of them
      had undergone hemodialysis, and also had a history of eating Sugihiratake
      (Pleurocybella porrigens), an autumn mushroom without known toxicity. Since
      clinical details of this type of encephalopathy remain unknown, we analyzed the
      clinical, radiological and electroencephalographic (EEG) features of ten cases of
      this encephalopathy in Yamagata prefecture. The summary of the present study is
      as follows: 1. Ten patients had chronic renal failure, and seven underwent
      hemodialysis. 2. Each patient had a history of eating Sugihiratake within 2-3
      weeks of the onset of neurological symptoms. 3. The onset was subacute; the
      initial symptoms were tremor, dysarthria, and/or weakness of the extremities,
      which lasted an average of 4.5 days (ranging from 2 to 11 days), followed by
      severe consciousness disturbance and intractable seizures, resulting in status
      epilepticus in 5 patients. Myoclonus was also seen in 4 patients and Babinski
      reflex in 3. 4. Brain CT and MRI examinations were unremarkable in the early
      stages of the disease. Three to eight days after onset, however, conspicuous
      lesions appeared in the areas of the insula and basal ganglia in 6 patients. On
      MRI, these brain lesions were hyperintense on T2-weighted and FLAIR images, and
      hypointense on T1-weighted images. 5. EEG examination was performed in 6
      patients, all of whom showed abnormal EEG findings. Periodic synchronous
      discharge (PSD) was seen in 2 patients, spike and wave complex in one patient,
      and non-specific slow waves in 3. 6. Prognosis was different from case to case.
      Three patients died at 13, 14, and 29 days after onset. Two patients still showed
      persistent disturbance of consciousness one month after onset. One patient showed
      parkinsonism after recovering from consciousness disturbance. Four patients
      recovered nearly completely around one month after onset In 3 of the 4 recovered
      patients, renal failure was not severe and they did not need to undergo
      hemodialysis. This suggests that the degree of renal failure is a key for the
      prognosis of this type of encephalopathy. The present study suggests that this
      endemic disease is a newly recognized clinical entity of encephalopathy.

PMID- 15729877
TI  - [Prenatal diagnosis for neuromuscular diseases].

PMID- 15729878
TI  - [Thyrotoxic encephalopathy showing reversible diffusion-weighted imaging
      abnormalities].
AB  - A 31-year-old man was transferred to our emergency room (ER) with acute onset of
      high-grade fever and consciousness disturbance. His consciousness at ER was
      severely disturbed with restlessness. No apparent focal neurological signs were
      seen. MRI with diffusion-weighted images (DWI) showed high signal intensities at
      the corpus callosum, left cerebellar hemisphere, left deep white matter and right
      middle cerebellar peduncle. These lesions were low signals in apparent diffusion
      coefficient(ADC) map, indicating cytotoxic edema. EEG showed enhanced fast waves
      seen in predominantly frontal regions. CSF examination was normal except elevated
      initial pressure of 210 mmH2O. He was treated with high dose dexamethasone and
      acyclovir. His consciousness and high-grade fever with systemic inflammatory
      responses were dramatically improved after these treatments. Subsequent data
      showed hyperthyroidism with anti-thyroid stimulating hormone receptor antibodies.
      This case was thought to be a thyrotoxic encephalopathy with beneficial response
      to corticosteroid therapy. Abnormalities seen in DWI and EEG were normalized ten
      days later.

PMID- 15729879
TI  - [A case of Creutzfeldt-Jakob disease with a point mutation of prion protein at
      codon 180].
AB  - A 67-year-old woman was admitted to our hospital with progressive aphasia. There
      was no family history of similar diseases or any history of dura transplantation.
      Cranial magnetic resonance imaging (MRI) showed high signal areas in the temporal
      and parietal cortex predominantly on the left side on both T2-weighted images and
      on diffusion-weighted images. There were no periodic synchronous discharges
      observed on the electroencephalogram. As prion protein gene codon 180 point
      mutation (Val/Ile) was detected, we diagnosed her as having Creutzfeldt-Jakob
      disease (CJD). The characteristics of CJD of this type differ from those of
      sporadic CJD. To date, few papers on CJD with point mutation of codon 180 have
      been reported from Japan.

PMID- 15729880
TI  - [A case of subacute myelitis associated with primary Sjogren syndrome showing no
      MRI abnormality and diagnosed by somatosensory evoked potentials].
AB  - We describe a case of Sjogren syndrome presenting with subacute transverse
      myelopathy that improved in response to steroid therapy. A 55-year-old woman with
      a history of NIDDM developed progressive sensory disturbance and weakness of the
      both legs, and micturition disturbance during a 6-month period, resulting in
      walking difficulty. On admission, neurological examination revealed paraplegia
      with extensor plantar reflex and sensory disturbance below Th 6 level. Lumbar
      puncture disclosed a normal cell count and a mild elevation of protein in the
      CSF. As subacute myelitis at the level of Th 6 was suspected, spinal plain and
      enhanced MRI was performed, which revealed no abnormalities. In contrast, tibial
      somatosensory evoked potential (SEP) could not be evoked while median SEP was
      almost normal, indicating thoracic cord involvement. She was diagnosed with
      primary Sjogren syndrome based on xerostomia, apple-tree appearance in parotid
      sialography, mononuclear cell infiltration in the salivary gland biopsied, and
      elevated anti-SS-A and SS-B antibody titers. We considered that her myelopathy
      was associated with Sjogren syndrome, and started steroid pulse therapy. After
      three courses of steroid pulse therapy followed by oral prednisolone, she showed
      clinical and SEP improvements. It is conceivable that the present case may
      represent Sjogren syndrome complicated with myelopathy that shows no MRI
      abnormality and well responds to steroid therapy. SEP can be a valuable tool for
      assessing the presence and severity of spinal cord involvement, and the efficacy
      of treatments.

PMID- 15729881
TI  - [Reversible posterior leukoencephalopathy syndrome: experience in 3 cases].
AB  - We report 3 cases with reversible posterior leukoencephalopathy syndrome (RPLS)
      accompanied by eclampsia or hypertensive encephalopathy. RPLS may develop in
      patients who have eclampsia or hypertensive encephalopathy or who are
      immunosuppressed. The findings on neuroimaging are characteristic of subcortical
      edema without infarction. A 27-year-old primigravida developed eclampsia at 37
      weeks of gestation. MRI was performed 4 hours after the onset. The FLAIR sequence
      delineated extensive hyperintense lesions in the temporal and occipital lobe
      bilaterally. MR angiography(MRA) performed 6 days after the onset of symptoms
      clearly demonstrated intracranial vasospasm. Follow up MRI and MRA were performed
      3 weeks after the onset. The MRI showed slight residual hyperintensity in the
      occipital lobe. The MRA showed the disappearance of the vasospasm. A 39-year-old
      woman on the 8th postpartum day presented with thunderclap headache, which led to
      a search for SAH. She visited our hospital, whose high arterial blood pressure
      (220/110 mmHg) was observed. Both CT and MRA were normal. MRI revealed
      abnormalities in the parieto-occipital regions bilaterally. Treatment of
      hypertension led to resolution of the posterior leukoencephalopathy. A 38-year
      old woman on the 11th postpartum day suddenly developed vertigo, visual
      disturbance and generalized convulsion. MRI was performed 7 days after the onset.
      The FLAIR sequence delineated extensive hyperintense lesions in the occipital
      lobe bilaterally. MRA clearly demonstrated diffuse intracranial vasospasm. MRA
      performed 3 weeks after the onset showed the disappearance of the vasospasm. In
      conclusion, our experience suggests that the MRI and MRA noninvasively provide
      valuable findings which are complementary in the diagnosis and follow-up
      examination of a brain edema and vasospasm in RPLS.

PMID- 15729882
TI  - [A rare case of aqueductal stenosis due to venous angioma].
AB  - Aqueductal stenosis is induced by widely various causes. These causes include
      congenital stenosis, tumor or inflammation. Among them vascular malformation is a
      very rare cause. In this paper we present a rare case of aqueductal stenosis
      caused by venous angioma. The patient was a 28-year-old female, who suffered from
      headache and double vision. On admission, CT and MRI showed lateral and third
      ventricular dilatation not but fourth ventricle, suggested aqueductal stenosis.
      Gd-DTPA enhanced T1-weighted MR image showed an abnormal draining vein passing
      through the orifice of the aqueduct. Angiography demonstrated the umbrella sign
      which was specific sign of the venous angioma. We performed endoscopic third
      ventriculostomy. Postoperative neuroradiological examination showed shrinkage of
      the ventricles and the symptom of the patient improved markedly. In the past
      literatures, five cases of aqueductal stenosis due to venous angioma have been
      reported. Although venous angioma is congenital, all five cases had been
      symptomatic at adult stage. Detailed evaluation of pre-and post-operative MRIs
      suggest that aqueductal stenosis induced enlargement of the lateral and third
      ventricles, which led narrowing of the suprachiasmatic cistern and the peri
      mesencephalic cistern, and downward displacement of medulla and tonsil into the
      foramen magnum. As a result, hydrocephalus is aggravated gradually.

PMID- 15729883
TI  - [Diagnosis of adult type of Niemann-Pick disease (type C) in two brothers by
      filipin staining of bone marrow smears].
AB  - Niemann-Pick disease, type C (NPC) is a neurometabolic genetic disorder that is
      distinguished from other types of Niemann-Pick disease by its later onset, more
      insidious progression, variable visceromegaly, and abnormalities of intracellular
      cholesterol metabolism. We report cases in 18-year-old and 20-year-old brothers
      who presented with disinhibition and involuntary movement of their hands. Both
      brothers presented various signs such as dementia, vertical supranuclear
      ophthalmoplegia (VSO), dysarthria, axial and limb dystonia, hyperreflexia,
      pathologic reflex, cerebellar ataxia, as reported. They also presented startle
      response. Brain MRI showed diffuse cerebral atrophy and abdominal CT reveals
      hepato-splenomegaly in both patients. These cases were suspected to be NPC based
      on dementia, VSO, cerebellar ataxia, hepato-splenomegaly and foam cells in the
      bone marrow. Generally, the diagnosis of NPC is based on deficient cholesterol
      esterification and excessive lysosomal filipin staining in cultured skin
      fibroblasts. However, culture of fibroblasts obtained from a biopsied skin
      samples is slow. We have rapidly made the diagnosis of NPC in our patients by
      filipin staining of foam cells from bone marrow. This diagnostic process using a
      bone marrow smear is more convenient and rapid than previous methods using
      cultured skin fibroblasts.

PMID- 15729884
TI  - [Dorsolaterally organized sequestration of cervical disc herniation].

PMID- 15729885
TI  - [An autopsy case of dementia with Lewy bodies which was clinically suspected to
      be Parkinson's disease complicated with Alzheimer-type dementia].

PMID- 15729886
TI  - [A study on inoculum density and reproducibility of drug susceptibility testing
      by BACTEC MGIT 960].
AB  - OBJECTIVE: The BACTEC MGIT 960 drug susceptibility system (MGIT AST) has been
      recently introduced in Japan. The issue of discordant MGIT results compared with
      the conventionally used Ogawa method has been raised. It has been speculated that
      discordant results might be due to MGIT inoculum density since there is no
      standardization step other than dilution of growth for tubes beyond 2 days after
      MGIT turns out to be positive. In this study, we examined the reproducibility of
      the MGIT AST system. MATERIALS AND METHODS: Nineteen sputum specimens from drug
      resistant and susceptible pulmonary tuberculosis patients were processed with CCE
      pretreatment reagent (Japan BCG), inoculated into 3 MGIT tubes, and loaded into
      the MGIT 960. Inocula for MGIT AST were prepared 1, 3, and 5 days after MGIT
      tubes became positive. Cultures on day 3 and 5 were diluted 1: 5 with saline. Ten
      fold dilutions from each positive culture were plated on Middlebrook 7H11 agar
      plates for CFU determination. MGIT AST results were compared with those of the
      conventional proportion method on Ogawa egg and Vite-spectrum (Kyokuto), or
      Pyrazinamidase (Pzase) assay and Kyokuto PZA test. RESULTS AND CONCLUSION: A
      total of 15 specimens were culture positive in all 3 tubes. Four of 19 cases were
      removed from the analysis because of negative cultures in one or more tubes.
      Three of 4 culture negative cases were MDR-TB. Colony counting showed the mean
      CFU/ml of inocula prepared from tubes 1, 3, and 5 days after MGIT tube became
      positive were 3.6 x 10(6), 1.6 x 10(6), 3.1 x 10(6), respectively. There was no
      significant difference although the CFU range was wide (8 x 10(4)-2 x 10(7)).
      MGIT AST results were consistent among 3 inocula. Moreover, overall concordance
      rates between MGIT AST and the conventional methods were over 90% for 5 first
      line antituberculosis drugs. These results indicate that the BACTEC MGIT 960
      system is very useful for rapid diagnosis of drug resistant tuberculosis.

PMID- 15729887
TI  - [Are tuberculosis advisory committees well-functioning?].
AB  - PURPOSE: To evaluate the function status of TB advisory committee to assess
      treatments of tuberculosis. OBJECT AND METHOD: Estimate by questionnaire sheets
      to public health nurses attending to seminars on tuberculosis at Research
      Institute of Tuberculosis. RESULT: 137 answers are available for analysis. Of
      these, 57 (41.6%) TB advisory committees are estimated not to assess treatments
      of tuberculosis at all and/or to assess treatments without necessary informations
      on drug sensitivity in more than around half of the cases. In 13 (16.3%)
      committees of the other 80, many cases are in fact self-assessed. Number of
      committees that are estimated to functioning well is only 44 (32.1%). CONCLUSION:
      Many TB advisory committees are estimated to be malfunctioning from the stand
      point of assessments of treatment. As TB advisory committee is one of key agency
      to control drug-resistant tuberculosis, its reform and revitalization are
      urgently needed.

PMID- 15729889
TI  - [Diagnostic key-point of the pulmonary tuberculosis].
AB  - I have been engaged in the diagnosis and treatment of pulmonary tuberculosis for
      about 25 years. I have presented many interesting tuberculosis cases such as
      cavity, nodule, infiltration, miliary pattern, and bronchial tuberculosis. I
      summarized that the key point of the diagnosis for pulmonary tuberculosis is, 1)
      X-ray diagnosis shows no specific findings, so it is important to remind
      pulmonary tuberculosis as not unusual disease. I will make a proposal to insert
      pulmonary tuberculosis in the guideline for the diagnosis of pneumonia by the
      Japanese Respiratory Society. 2) Sputum PCR examination is very rapid and useful
      diagnostic method. The diagnostic evaluation of PCR is equal or over that of AFB
      culture. 3) CT diagnosis is useful for the detection of minimal pulmonary shadow
      or cavity lesion. 4) Brocho-fiberscopic examination is useful for the detection
      of the Mycobacterium in the bronchial brushing smear or washing samples. We
      should suspect bronchial tuberculosis in the cases with strongly positive sputum
      smear without cavity shadow. 5) The rate of complication with diabetes mellitus
      is significantly higher than that of 10 years ago in adult male tuberculosis
      patients. Recently 1 of 4 patients complicated with diabetes mellitus in adult
      male patients.

PMID- 15729888
TI  - [Usefulness of a novel diagnostic method of tuberculosis infection, QuantiFERON
      TB-2G, in an outbreak of tuberculosis].
AB  - OBJECTIVE: The purpose of this study was to evaluate QuantiFERON TB-2G (QFT), a
      novel method of detecting tuberculosis infection among contacts of a tuberculosis
      patient by determining the whole-blood interferongamma response to the specific
      antigens. SUBJECTS AND METHODS: A teacher of a college who had been coughing for
      the preceding two months was diagnosed with smear-positive tuberculosis. About
      270 students of the college were considered to have been exposed to tuberculosis
      infection, of whom 73 were in closer contact with the index case because they
      participated in a one-week group excursion attended by the teacher. Two of the
      contact students developed active tuberculosis shortly thereafter. Tuberculin
      tests were conducted to almost all students, and QFT was performed for only those
      with tuberculin reactions having erythema diameters of 30 mm or larger. RESULTS:
      Tuberculin tests of students, all of whom had been vaccinated with BCG at least
      once, revealed that the distribution of the close contact group was slightly
      shifted to right (larger side) than those with less close contacts. The QFT
      positive rate for close contacts was 45.5%, while that for less close contacts
      was only 7.1%, which obviously indicates that QFT is hardly affected by the
      tuberculin allergy due to past BCG vaccination. The distribution of interferon
      gamma measurements (log-transformed) of the close contacts showed typical
      bimodality, one mode representing the infected, another the non-infected. This
      was not clear for the less close contacts. The correlation of interferon-gamma
      measurements (log-transformed) with tuberculin reaction erythema size was weak,
      if not non-significant. CONCLUSION: It was concluded that QFT was a useful method
      for diagnosing tuberculosis infection and was unaffected by the BCG-caused
      tuberculin allergy. In the case of the outbreak mentioned above, QFT greatly
      reduced the indication of chemoprophylaxis, from 28% of all the contacts solely
      based on tuberculin test to only 7%. Although there remains some problems to be
      overcome for QFT to be widely used with high confidence, this technology will
      provide a high possibility for wider and more accurate indication of
      chemoprophylaxis and will be one of the essential tools of tuberculosis control
      of the 21st century in Japan.

PMID- 15729890
TI  - [A cultural history of tuberculosis].
AB  - Tuberculosis (TB) has a long history. Regarding terminology, TB has, roughly
      speaking, three stages. These are, PHTHISIS, CONSUMPTION and TUBERCULOSIS. Each
      stage has its own meanings and characteristics. In the second stage consumption,
      TB was thought to be responsible for the patients' beauty and creativity. This
      kind of romanticization can be seen both in the West and East, not only in
      literature but also in paintings.

PMID- 15729891
TI  - [Molecular pathogenesis in tuberculosis complicated with AIDS].
AB  - HIV-1 infection is a major cause of worldwide epidemic of tuberculosis. There is
      increasing clinical evidence that coinfection with M. tuberculosis accelerates
      progression of AIDS. We found that, in vivo, HIV-1 load and mutation increase in
      involved lung segments in patients with pulmonary tuberculosis. We also reported
      that Mycobacterium tuberculosis stimulates HIV-1 replication by enhancing
      transcription on the 5' LTR in a macrophage cell line, THP-1, in vitro. In
      contrast, HIV-1 replication is suppressed by M. tuberculosis infection of
      monocytes derived macrophages (MDM) or differentiated monocytic THP-1 cells. We
      observed that HIV-1 5' LTR function was repressed in PMA differentiated THP-1
      cells after co-infection with M. tuberculosis. Point mutations in C/EBP beta
      binding domains of the HIV-1 LTR negative regulatory element (NRE) abolished
      promoter repression. Monocyte-derived macrophages and differentiated THP-1 cells
      increased expression of the 16kDa inhibitory form of C/EBP after M. tuberculosis
      co-infection. Bronchoalveolar lavage cells obtained from normal controls and
      alveolar macrophages from uninflamed lung of tuberculosis patients also expressed
      the 16kDa inhibitory form of C/EBP. However, alveolar macrophages from lung
      segments involved with pulmonary tuberculosis had markedly reduced C/EBP
      expression. These data suggest that 16kDa isoform of C/EBP plays an important
      role for the control of HIV-1 replication in macrophages. We propose derepression
      of HIV-1 LTR mediated transcription as one mechanism for enhanced HIV-1
      replication observed in pulmonary tuberculosis. Since the cellular immune
      response in pulmonary tuberculosis requires lymphocyte/macrophage interaction, a
      model system was developed in which lymphocytes were added to AM. Contact between
      lymphocytes and AM reduced inhibitory C/EBP beta, activated NF-kappaB and
      enhanced HIV-1 replication. If contact between lymphocytes and macrophages was
      prevented, inhibitory C/EBP beta expression was maintained and the HIV-1 long
      terminal repeat (LTR) was not maximally stimulated although NF-kappaB was
      activated. Antibodies which cross-linked macrophage expressed B-7, VCAM and CD-40
      were used mimic lymphocyte contact. Cross-linking antibodies abolished inhibitory
      C/EBP beta expression; however, the HIV-1 LTR was not maximally stimulated and NF
      kappaB was not activated. Maximal HIV-1 LTR stimulation required both lymphocyte
      derived soluble factors and cross-linking of macrophage expressed co-stimulatory
      molecules. These results demonstrate that neither contact nor soluble factor(s)
      are sufficient to maximally enhance HIV-1 LTR activity in macrophages. Contact
      between activated lymphocytes and macrophages is necessary to downregulate
      inhibitory C/EBP beta, thereby derepressing the HIV-1 LTR. Lymphocyte derived
      soluble factor(s) activate NF-kappaB, further enhancing the HIV-1 LTR.

PMID- 15729892
TI  - Serum haemolytic complement levels in German Dahlem Red chickens are affected by
      three major genes (naked neck, dwarf, frizzled) of tropical interest.
AB  - German Dahlem Red chickens with three different major genes of tropical interest:
      Nana- (naked neck), Ff- (frizzled) and dw- (dwarf), respectively, were tested for
      serum haemolytic complement, which is essential in innate host defence against
      infectious agents. Eight different combinations of genes for body size and
      feather coverage were evaluated. Significant differences both for both the
      calcium-dependent (classical, CPW) and the calcium-independent (alternative, APW)
      complement titres were found between the phenotypes. Phenotype nanaffDw- showed
      the highest complement status. The frizzled (Ff-) gene had a negative influence
      on APW titres, whereas the dwarf (dw-) gene had a negative influence on CPW
      titres. The naked neck (Nana-) gene had various influences on the haemolytic
      complement status. All tested hens had MHC (B) 21 haplotypes, whereas the gene
      for dwarfism appeared to be linked with the B19 haplotype. It was concluded that
      introducing major genes (Nana-, dw-, Ff-) to conquer environmental stress in hot
      climates can have a negative impact on certain aspects of the innate immunity of
      poultry.

PMID- 15729893
TI  - A serological investigation into contagious caprine pleuropneumonia (CCPP) in
      Ethiopia.
AB  - For a comparison of serological tests for CCPP, sera from 767 goats were
      examined. They were subjected to three tests: complement fixation test (CFT) with
      Mycoplasma capricolum subspecies capripneumoniae antigen; blocking ELISA (B
      ELISA) with Mycoplasma capricolum subspecies capripneumoniae antigen; and CFT
      with Mycoplasma mycoides subspecies mycoides small colony type antigen.
      Antibodies were detected by these three tests in 23%, 2% and 12%, respectively,
      of sera from districts in which CCPP had not been reported, and in 60%, 83% and
      87%, respectively, in sera from areas in which CCPP had been reported. The
      specificity of the tests is discussed. The use of the B-ELISA test for the
      diagnosis and for epidemiological studies of CCPP is strongly recommended.

PMID- 15729894
TI  - Evidence of Mycoplasma hyopneumoniae infection among slaughtered pigs in Sri
      Lanka.

PMID- 15729895
TI  - Immunogenicity of a locally produced Newcastle disease I-2 thermostable vaccine
      in chickens in Uganda.
AB  - A locally-produced Newcastle disease (ND) I-2 thermostable vaccine of embryo
      infective dose (EID50) 10(8.5) per ml was administered to 100 laboratory chickens
      in four test groups, each of 25 birds. It was given by the eye-drop method, in
      drinking water, in drinking water freshly medicated with levamisole, or using
      millet grains as a vaccine carrier. A fifth control group consisting of 25 birds
      received the heat-sensitive La Sota vaccine (EID50 10(9) per ml) by the eye-drop
      method. The immunological responses were monitored by the enzyme-linked
      immunosorbent assay (ELISA) ND antibody technique using serum samples collected
      from 18 birds in each group at 3-week intervals for 3 months. The overall mean ND
      antibody log(10) titres and percentage positivities were 3.1, 88%; 2.9, 70%; 3.0,
      83%; 3.2, 87% and 3.3, 87%, respectively. The use of water alone or medicated
      with levamisole for vaccine administration produced significantly lower ND
      antibody titres only in the first 3 weeks. The immunogenicity shown by the I-2
      vaccine as a potential vaccine is discussed in relation to free-range poultry
      management conditions in Uganda.

PMID- 15729896
TI  - Impact assessment of a community-based animal health project in Dollo Ado and
      Dollo Bay districts, southern Ethiopia.
AB  - Participatory methods were used to assess the impact of a community-based animal
      health worker (CAHW) project in two remote pastoralist districts of Ethiopia. The
      CAHW project had been operating for 3 years at the time of the assessment.
      Participatory methods were standardized and repeated with 10 groups of informants
      in the project area. The assessment showed significant reductions in disease
      impact for diseases handled by CAHWs compared with diseases not handled by CAHWs.
      In camels, there was significant reduction (p < 0.001) in the impact of mange,
      trypanosomosis, helminthosis, anthrax and non-specific respiratory disease. In
      cattle there was a signficant reduction (p < 0.001) in the impact of blackleg,
      anthrax and helminthosis. In sheep and goats there was a sign reduction (p <
      0.001) in the impact of mange, helminthosis, contagious caprine pleuropneumonia,
      orf and non-specific diarrhoea. In order of importance, these reductions in
      disease impact were attributed to (1) increased use of modern veterinary services
      provided by CAHWs, (2) vaccination campaigns involving CAHWs, (3) good rainfall
      and availability of grazing and (4) decreased herd mobility. Decreased herd
      mobility was also associated with negative impact of tick infestation. Community
      based animal health workers were considered to be highly accessible, available,
      affordable and trustworthy relative to other service providers. They were also
      perceived to be suppliers of a good quality service. Specific types of positive
      impact attributed to CAHW activities were increases in milk, meat, income and
      draught power.

PMID- 15729897
TI  - Risk factors for lamb mortality in Sahelian sheep on a breeding station in Ghana.
AB  - A retrospective cohort study was designed to examine the effect of sex, season of
      birth, type and year of birth, and birth weight on lamb mortality. The method
      used involved analysis of breeding records for Sahelian sheep kept on a breeding
      station at Pong-Tamale in northern Ghana from 1994 to 2000. The pre-weaning and
      post-weaning mortalities were 10% (n = 505) and 19% (n = 453), respectively,
      while the overall mortality from birth up to 12 months of age was 28% (n = 505).
      Compared to the pre-weaning period, the post-weaning period recorded
      significantly higher proportions of deaths in male, single-born, lambs born in
      the rainy or dry seasons, and in lambs with low (<3 kg) or high (> or =3 kg)
      birth weight. The odds and risks of death for male lambs were about one and a
      half times those for females at post-weaning. Lambs born in the dry season had
      significantly higher mortality than those born in the rainy season. Lambs that
      died by the time of weaning were not significantly different in weight at birth
      from those that survived. The mean birth and weaning weights of single-born lambs
      were significantly higher than those for twins. The mean pre-weaning ADG was
      significantly higher in lambs born as singles compared to that for twins. The
      season of birth had influence on mean birth weight, with those born in the rainy
      season having significantly higher weights than those born in the dry season. The
      year of birth significantly affected birth weight, weaning weight, weight at 12
      months and ADG at all stages of the lambs' life. The study concluded that the
      most significant risk factors for lamb mortality included sex of the lamb, season
      of birth and birth weight. The last two could be manipulated, to some extent, to
      reduce lamb mortality.

PMID- 15729899
TI  - Utilization of ensiled sweet potato (Ipomoea batatas (L.) Lam.) leaves as a
      protein supplement in diets for growing pigs.
AB  - Four diets were formulated with protein from fishmeal (FM), groundnut cake (GC),
      ensiled sweet potato (Ipomoea batatas L. (Lam.)) leaves (SP) or ensiled sweet
      potato leaves with lysine (SPL). In experiment 1, 24 crossbred (Large White x
      Mong Cai) growing pigs were allocated randomly by sex into four groups of six
      pigs and given one of four diets. Experiment 2 was conducted using 16 crossbred
      pigs (Large White x Mong Cai) at four farms. On each farm, pigs were allocated to
      two experimental groups. One group was fed the FM diet and the other group the
      SPL diet. In experiment 1, the daily live weight gains (DLWG) were significantly
      higher (p < 0.05) for the FM and SPL treatments (542 and 536 g/day, respectively)
      than for the GC and SP treatments (464 and 482 g/day, respectively). Feed intake
      was highest (2.0 kg/day) for the SPL and lowest (1.7 kg/day) for the GC treatment
      (p < 0.05) and feed conversion ratio (FCR) was highest (3.8 kg/kg gain) for SP
      and lowest (3.5 kg/kg gain) for FM (p < 0.05). There were no significant
      differences for carcase measurements among diets (p > 0.05). The feed cost per kg
      live weight gain was lowest for the SP and SPL diets compared to the FM and GC
      diets. The results of experiment 2 show that there were no significant
      differences in feed intake, DLWG and FCR between the two diets (p > 0.05). In
      conclusion, sweet potato leaves can replace fishmeal and groundnut cake in
      traditional Vietnamese diets for growing pigs.

PMID- 15729898
TI  - Intake of essential fatty acids by growing-finishing pigs kept on smallholdings
      in central Vietnam.
AB  - The intake of linoleic acid (LA) and alpha-linolenic acid (ALA) in relation to
      average daily weight gain (ADG) was studied in growing-finishing pigs kept on
      smallholdings in Central Vietnam. Groups of three piglets each were assigned
      randomly to 12 farms, where they were fed on local feedstuffs according to the
      farmer's choice but were given a restricted amount of dry matter according to a
      preset feeding regimen. On arrival at the farms, the pigs weighed 10.4 +/- 0.9 kg
      (mean +/- SD, n = 36) and at 130 days of age they weighed 45.4 +/- 9.6 kg.
      Dietary LA concentration ranged from 1.34 to 2.41 g/MJ metabolizable energy (ME)
      and ALA from 0.06 to 0.33 g/MJ ME. On a farm level, dietary LA and ALA
      concentrations were significantly correlated with their concentrations in adipose
      tissue, both correlation coefficients being 0.63. Dietary protein concentration
      and protein:energy ratio were significantly correlated with ADG, the correlation
      coefficients being 0.68 and 0.64. For individual piglets there were significant
      correlations between either LA or ALA in adipose tissue and ADG, the correlation
      coefficients being 0.37 and 0.45. Dietary protein concentration or protein:energy
      ratio was correlated with the dietary contents of LA and ALA. It is uncertain
      whether LA and ALA intake had a causal relationship with ADG. Since dietary LA
      levels were above the LA requirement, LA intake may not have limited growth. It
      is suggested tentatively that, through enhanced disease resistance,
      supplementation with ALA of the diets on the farms studied might have a positive
      influence on ADG.

PMID- 15729900
TI  - Interview with Mary Stefl, Ph.D., Professor and Chair, Department of Health Care
      Administration, Trinity University, San Antonio, Texas.

PMID- 15729901
TI  - The five stages of physician reaction to change.

PMID- 15729902
TI  - Lessons learned: seven keys to a successful replacement hospital project.

PMID- 15729903
TI  - Overview of investment and financing trends in the hospital industry.

PMID- 15729904
TI  - Teams as the key to organizational communication.

PMID- 15729905
TI  - Marketing telehealth to align with strategy.
AB  - Telehealth is a twenty-first century solution to an old problem-how to deliver
      quality health services with shrinking resources. Telehealth enables healthcare
      providers to interact with and monitor patients remotely, thus adding value to
      service delivery models. On occasion, telehealth can substitute for live
      encounters, saving time and resources. Furthermore, as the geriatric population
      increases, telehealth will support independent living by supplementing the
      existing network of care. To be used most effectively, however, telehealth
      services must be carefully planned and executed. This study investigated
      management practices used to promote telehealth services, focusing on strategic
      goals for adopting telehealth. Interviews with senior managers from 19 home
      health agencies identified three strategic goals for adopting telehealth: (1)
      clinical excellence, (2) technological preeminence, and (3) cost containment.
      Organizational documents were analyzed to determine the extent to which the
      telehealth program was featured in marketing materials. Documents included the
      organization's brochure, newspaper ads and articles, and each home health
      agency's web site. Results showed that marketing practices vary widely but are
      correlated with motivations to adopt telehealth. The organizations with the
      highest marketing scores emphasize clinical excellence as a major reason for
      using telehealth, whereas those with the lowest marketing scores tend to focus on
      cost containment. Although this study focused on management practices in home
      health agencies, results are applicable to hospital and outpatient services as
      well as to other community-based programs. Using a strategic management
      framework, the authors offer recommendations to help organizations develop
      effective marketing approaches for telehealth programs.

PMID- 15729906
TI  - Building an understanding of the competencies needed for health administration
      practice.
AB  - Rapid change in the healthcare environment has pressured healthcare
      organizations, health management professional associations, and educational
      institutions to begin examining more carefully what it means to be a fully
      competent healthcare executive. As a result, interest in healthcare management
      core competencies has increased. Most competency development initiatives seek to
      build consensus and typically result in the generation of five or six broad
      competency domains--but consensus around what? Most competency initiatives are
      based on literature reviews and consensus-building efforts. Typically, such
      efforts in healthcare management have involved defining general competency
      domains and attempting to specify representative behavioral exemplars that
      demonstrate mastery of the general competency domain. This study describes an
      approach that used a purposeful sample of ACHE affiliates who represent different
      geographic regions and health industry segments to construct a framework composed
      of critical healthcare issue clusters. A panel of healthcare executives then
      specified five sets of entry-level behavioral competencies that would be required
      to address the clusters of critical issues. Although the behavioral competencies
      identified by the executives in this study are anchored to a framework, their
      empirical association with performance has not been tested. Before implementing
      broad curriculum redesign, the effect of these competencies on performance should
      be established. Additionally, competencies should be examined in the context of
      potential moderating influences such as specific educational program focus,
      educational delivery format, and type and preparation of students entering
      healthcare management education programs. Competency, competencies, competency
      models, and competency-based training are all Humpty Dumpty words meaning only
      what the definer wants them to mean. The problem comes not from malice [or]
      stupidity... but instead from some basic procedural and philosophical differences
      among those racing to define the concept and to set the model for the way the
      rest of us will use competencies (Zemke 1982).

PMID- 15729907
TI  - Predicting the effect of extrinsic and intrinsic job satisfaction factors on
      recruitment and retention of rehabilitation professionals.
AB  - The purpose of this study was to ascertain which extrinsic and intrinsic job
      satisfaction areas are most predictive of rehabilitation professionals' career
      satisfaction and desire to stay on the job. This article discusses the results of
      a survey conducted on practicing occupational therapists, physical therapists,
      and speech-language pathologists regarding factors that contribute to career
      satisfaction and desire to stay on the job. Five hundred surveys were mailed to
      each profession; 463 were returned, of which 328 were able to be analyzed.
      Results from regression analysis showed that intrinsic factors such as
      professional growth and having a work environment in line with personal values
      are more significant in predicting career satisfaction than are extrinsic factors
      such as pay and continuing education. These same intrinsic factors are also
      significant in predicting the rehabilitation professional's desire to stay on the
      job. These findings are significant to healthcare managers desiring to recruit
      and retain qualified occupational therapists, physical therapists, and speech
      language pathologists. In addition to extrinsic benefits such as pay, healthcare
      managers need to focus on provision of intrinsic factors such as opportunities
      for professional growth, recognition of accomplishments, and opportunities for
      departmental input to motivate rehabilitation professionals.

PMID- 15729908
TI  - Achieving statistically significant improvements in patient satisfaction scores
      in a community hospital through the development of a service excellence model.

PMID- 15729909
TI  - Light direction from shad(ow)ed random Gaussian surfaces.
AB  - Three human observers estimated the illumination direction for samples of random
      Gaussian surfaces illuminated by a collimated beam from random directions. These
      stimuli appear as 'texture' due to shading and shadowing (the surface on the
      microscale was Lambertian of uniform albedo; thus texture appears only through
      shading and shadowing). We found that observers were able to estimate the azimuth
      of the source with remarkable accuracy. In the shading regime (no shadows) the
      observers committed 180 degrees azimuth errors with 50% probability, whereas in
      the shadow-dominated regime they were able to avoid this convex/concave confusion
      to a large extent. They evidently relied on second-order statistics in the
      shading regime and used an unidentified first-order cue in the shadow regime. The
      elevations of the source were also estimated with remarkable precision. We
      attribute this to the statistical homogeneity of the sample which can apparently
      be exploited by the observers. Likely cues are the fraction of shadowed surface,
      average intensity and rms contrast. The ability of human observers to estimate
      the illumination direction from surface texture no doubt contributes to the
      ability to estimate the light field in scenes, which is a prerequisite to the
      photometric parsing of scenes (shape from shading, and so forth).

PMID- 15729910
TI  - Is light in pictures presumed to come from the left side?
AB  - For good ecological reasons humans assume that the illumination in pictures comes
      from overhead rather than from below. Recent work has also raised the possibility
      that the preferred angle of illumination is between 20 degrees and 30 degrees to
      the left of vertical, although the ecological basis for that is obscure. We
      describe two studies of this question. In study 1, twenty subjects looked in
      free, unrestricted vision, at a picture of a single 'bubble' which appeared
      either convex if the illumination was from above, or concave if the illumination
      was from below. There was no evidence in study 1 that illumination from the left
      produced a different appearance from illumination from the right, the preferred
      angle of illumination being 0.5 degrees to the right of vertical. In study 2, on
      forty subjects, there was fast presentation (200 ms) of an array of 16 bubbles,
      one of which, the target, was illuminated from the opposite direction to the
      others, and hence 'popped out' from the display, appearing concave if the others
      were convex, or vice-versa. The preferred angle of illumination for detection of
      the target was about 14 degrees to the left of vertical in study 2. The estimates
      from studies 1 and 2 did not differ significantly, and when combined gave a
      preferred angle of 9 degrees to the left of vertical. The reasons for the seeming
      discrepancy between studies 1 and 2, or the smaller overall effect than that
      found in previous studies are not clear since the methodologies seem equivalent.
      In both studies 1 and 2 there was a highly significant association between the
      direction of spontaneous head tilt and preferred direction of illumination, and
      this factor has not previously been taken into account in studies of the
      phenomenon. Contrary to the study of Sun and Perona (1998, Nature Neuroscience 1
      183-184), there was no association with handedness or other measures of
      functional lateralisation.

PMID- 15729911
TI  - Stereokinetic shapes and their shadows.
AB  - The visual space of phenomenal appearances has a complex geometry which cannot be
      reduced strictly to Euclidean or projective geometry. The distinctive nature of
      this space and its objects is evidenced paradigmatically by stereokinetic
      phenomena, which are perceptual objects in actual three-dimensional coming into
      being. Stereokinetic phenomena produce the appearance not only of corporeality
      but also, in certain circumstances, of shadows. By altering certain components of
      his experiments on the three-dimensional appearance of a truncated cone, in fact,
      Musatti discovered that on its white base floats some sort of shadow obscuring
      stretches of the white lines. These shadows are connected to phenomena of amodal
      presentations successively analysed by Kanizsa. The continuity of the unfolding
      in visual space of stereokinetic transformations produces a diversified series of
      percepts coming into being, shadows included, and highlights the role of
      configurational movement as a factor of formal unification, thereby proposing
      once again the hypothesis of assimilative factors as responsible for the field
      organisation of past experience.

PMID- 15729912
TI  - Shape-from-shading depends on visual, gravitational, and body-orientation cues.
AB  - The perception of shading-defined form results from an interaction between
      shading cues and the frames of reference within which those cues are interpreted.
      In the absence of a clear source of illumination, the definition of 'up' becomes
      critical to deducing the perceived shape from a particular pattern of shading. In
      our experiments, twelve subjects adjusted the orientation of a planar disc
      painted with a linear luminance gradient from one side to the other, until the
      disc appeared maximally convex-that is, until the luminance gradient induced the
      maximum perception of a three-dimensional shape. The vision, gravity, and body
      orientation cues were altered relative to each other. Visual cues were
      manipulated by the York Tilted Room facility, and body cues were altered by
      simply lying on one side. The orientation of the disc that appeared maximally
      convex varied in a systematic fashion with these manipulations. We present a
      model in which the direction of perceptual 'up' is determined from the sum of
      three weighted vectors corresponding to the vision, gravity, and body-orientation
      cues. The model predicts the perceived direction of 'up', contributes to our
      understanding of how shape-from-shading is deduced, and also predicts the
      confidence with which the 'up' direction is perceived.

PMID- 15729913
TI  - A biologically inspired algorithm for the recovery of shading and reflectance
      images.
AB  - We present an algorithm for separating the shading and reflectance images of
      photographed natural scenes. The algorithm exploits the constraint that in
      natural scenes chromatic and luminance variations that are co-aligned mainly
      arise from changes in surface reflectance, whereas near-pure luminance variations
      mainly arise from shading and shadows. The novel aspect of the algorithm is the
      initial separation of the image into luminance and chromatic image planes that
      correspond to the luminance, red-green, and blue-yellow channels of the primate
      visual system. The red-green and blue-yellow image planes are analysed to provide
      a map of the changes in surface reflectance, which is then used to separate the
      reflectance from shading changes in both the luminance and chromatic image
      planes. The final reflectance image is obtained by reconstructing the chromatic
      and luminance-reflectance-change maps, while the shading image is obtained by
      subtracting the reconstructed luminance-reflectance image from the original
      luminance image. A number of image examples are included to illustrate the
      successes and limitations of the algorithm.

PMID- 15729914
TI  - Are size illusions in simple line drawings affected by shading?
AB  - In a number of simple line drawings, such as the Muller-Lyer or Judd figures, we
      can experience strong distortions of perceived space-geometric illusions. One way
      of explaining these effects is based on the perspective information that can be
      read from the line drawings. For instance, the 'inappropriate constancy scaling'
      theory advocates that the inferred three-dimensional structure of the pictured
      object is used by the perceptual system to adjust the size of line-drawing
      components. Such a theory would predict that additional depth cues, for instance
      shading added to line drawings, should affect these illusions because they
      influence the three-dimensional appearance. We present here systematic
      measurements of the magnitude of length misjudgments in horizontal Muller-Lyer
      and Judd figures for three configurations: (i) pure line drawings, and with
      shading attached to (ii) the top, and (iii) the bottom of the figures. The latter
      two configurations are unambiguously interpreted as 'folded' structures with a
      horizontal edge behind the image plane or protruding from it, respectively. While
      we could not find any effect of shading in our experimental data, we did observe
      a length misjudgment in Judd figures that corresponds precisely to the asymmetry
      that can be observed in the Muller-Lyer illusion for inward and outward fins.
      This pattern of results is not consistent with notions of inappropriate constancy
      scaling but is fully coherent with the view that neural filtering mechanisms,
      which are affecting the perceived position of line intersections, are responsible
      for this type of geometrical illusions.

PMID- 15729915
TI  - Visual discrimination of spectral distributions.
AB  - Human observers seem to be able to use different features that classify materials
      with a large degree of accuracy. In this paper, we look at human perception of
      statistical properties of the spectral distribution in a scene. We investigated
      whether human observers can discriminate just as accurately between coloured
      textures that have a spectral distribution due either to shading only or to both
      shading and specular reflectance as between uniform colours. Thresholds for the
      discrimination of coloured textures are about 15 times as high as thresholds for
      the discrimination of uniform colours, provided there is a sharp transition
      between the two colours. However, the coloured texture thresholds are only 1.5
      times higher when we introduce a gradual transition between the two colours.
      There are also distinct qualitative differences in discrimination thresholds for
      different base colours. These differences cannot be predicted from discrimination
      thresholds for uniform colours. Human observers are surprisingly good at
      discriminating between a material edge and a shadow edge in complex scenes.
      Statistical differences in the orientation of the colour distributions in colour
      space might be used to accomplish this. In a second experiment we investigated
      how well observers can discriminate between two linear distributions in colour
      space that have the same base colour but different orientations. When we vary the
      line-length in R, G, B space, thresholds cannot be predicted completely by the
      conservation of the average distance between the two distributions. This means
      that observers use not only the maximum colour difference in the stimulus to do
      the task, but other cues are also involved.

PMID- 15729916
TI  - Perceived contrast explains asymmetries in visual-search tasks with shaded
      stimuli.
AB  - Shaded stimuli have traditionally been used in the context of three-dimensional
      (3-D) shape perception. Many studies have shown a persistent asymmetry in that a
      circle filled with a shaded gradient that is dark at the top and bright at the
      bottom (top-dark circle) is much easier to locate among top-bright circles than
      in the opposite arrangement (a top-bright circle among top-dark circles). The
      immediate 3-D interpretation of top-dark and top-bright circles as hollows and
      protuberances, respectively, and the asymmetry just described have been explained
      in terms of 3-D percepts. The work described here challenges this view: the
      results of the first experiment show that top-dark circles are perceived as
      having 10% higher contrast than top-bright circles of the same physical contrast.
      Experiment 2 replicates classical visual-search experiments but adding a new
      condition where target and distractors were subjectively equated in contrast. For
      five of six subjects, the ubiquitous asymmetry disappears in this condition.

PMID- 15729917
TI  - Budget windfall. National healthcare IT office sees funding restored.

PMID- 15729918
TI  - HHS offers recruitment rules.

PMID- 15729919
TI  - Executive defensive. As the Scrushy case finally goes before an Alabama jury, the
      Sarbanes-Oxley Act and its impact are also on trial.
AB  - With the trial of Richard Scrushy, left, finally under way in Alabama, it isn't
      just the former HealthSouth executive being scrutinized. It's the first courtroom
      test for the Sarbanes-Oxley Act of 2002, which holds CEOs accountable for false
      financial statements. Scrushy's defense attorneys have already begun laying the
      groundwork to blame underlings for the 2.64 billion dollar accounting fraud.

PMID- 15729920
TI  - Guilt by association. Case may tarnish healthcare industry.

PMID- 15729921
TI  - Reimbursements at risk. CBO forecasts growth in Medicare spending.

PMID- 15729922
TI  - Washington's latest. Parties' bills aim to set U.S. healthcare agenda.

PMID- 15729923
TI  - Only a start. HFMA offers billing guidelines for uninsured.

PMID- 15729924
TI  - Offering some help. Employers join forces to help uninsured worker.

PMID- 15729925
TI  - Overseeing oversight. Wellmark CEO resigns Board of Regents position.

PMID- 15729926
TI  - We dare not follow. Bush, Frist, Thomas have healthcare dreams others might call
      nightmares.

PMID- 15729927
TI  - No Toyota yet, but a start. A cadre of providers seeks to transform an
      inefficient industry--before it's too late.

PMID- 15729928
TI  - Experts at integration. Annual IHN 100 ranks top-performing networks.

PMID- 15729929
TI  - Shopping spree. Healthcare organizations are taking retail space to a new level,
      with income from cash registers helping to pad the bottom line.

PMID- 15729930
TI  - Minnesota standoff. Allina calls antitrust charges a misunderstanding.

PMID- 15729931
TI  - Social security. Scandal, poverty, and privatization: tales from Britain.

PMID- 15729933
TI  - How to prevent violence at work.

PMID- 15729934
TI  - Want reform? Talk to Bill.

PMID- 15729932
TI  - Porky pigs.

PMID- 15729935
TI  - Old king Coal comes back.

PMID- 15729936
TI  - Biotech believer.

PMID- 15729937
TI  - Susceptibility of IFN-gamma or IL-12 knock-out and SCID mice to infection with
      two microsporidian species, Encephalitozoon cuniculi and E. intestinalis.
AB  - Susceptibility of three strains of immunodeficient mice to two related
      microsporidian species Encephalitozoon cuniculi Levaditi, Nicolau et Schoen, 1923
      and Encephalitozoon intestinalis (Cali, Kotler et Orenstein, 1993) was compared.
      While both, severe combined immunodeficient (SCID) and interferon-gamma knock-out
      (IFN-gamma KO) mice, succumbed to either intraperitoneal (i.p.) or peroral (p.o.)
      (natural) infection with both parasites, only i.p. infection with E. cuniculi
      killed interleukin-12 knock-out (IL-12 KO) mice. IFN-gamma KO mice died earlier
      than SCID mice. Adoptive transfer of naive splenocytes from IFN-gamma KO mice did
      not protect the SCID mice from a lethal infection with either of the
      Encephalitozoon species. However, reconstituted mice survived significantly
      longer (P<0.05), thus indicating the role of IFN-gamma produced by host NK cells
      in the development of mechanisms of anti-microsporidial protective immunity. Non
      lethal outcome of the infection always correlated with the increase in CD8+ T
      lymphocyte subpopulation. Both E. intestinalis-infected IFN-gamma KO and IL-12 KO
      mice produced comparable levels of specific antibodies, suggesting that
      antibodies did not protect IFN-gamma KO mice from lethal infection.

PMID- 15729938
TI  - Two new species of isospora (Apicomplexa: Eimeriidae) from geckoes of the genus
      Rhacodactylus (Sauria: Gekkonidae) endemic to New Caledonia.
AB  - Coprological examination of New Caledonian geckoes of the genus Rhacodactylus
      Fitzinger, 1843 revealed two new species of coccidia. Isospora leachiani sp. n.
      from R. leachianus (Cuvier, 1829) has oval, colourless oocysts, measuring 21-26 x
      16-18.5 microm. Sporocysts are ellipsoidal, 11-12.5 x 6.5-8 microm, with distinct
      Stieda and substieda bodies. Oocysts of Isospora sykorai sp. n. from R. ciliatus
      (Guichenot, 1866) are elongately oval to cylindrical, 20-23.5 x 11-14 microm;
      sporocysts of this species are ellipsoidal, 10-11.5 x 7-8 microm, with a slightly
      pointed end and Stieda and substieda bodies. Infected geckoes did not exhibit any
      alteration of their health status.

PMID- 15729939
TI  - Fine structure and function of the genital pore of the female of Intoshia
      variabili (Orthonectida).
AB  - The genital pore of the female of Intoshia variabili Aleksandrov et Sljusarev,
      1992 is located on a transverse ring of non-ciliated cells. Before copulation it
      is occupied by 6-7 cells that develop in the epithelium and that for a time are
      beneath the surface. When fully developed, these cells contain many electron
      dense granules and their apical surface is covered with numerous microvilli.
      After copulation the granules disappear and the apical surface becomes smooth.
      The cells still form a plug closing the opening. After one larva pushes the pore
      cells out and escapes, others follow.

PMID- 15729940
TI  - Monogenoids from the gills of spiny eels (Teleostei: Mastacembelidae) in India
      and Iraq, proposal of Mastacembelocleidus gen. n., and status of the Indian
      species of Actinocleidus, Urocleidus and Haplocleidus (Monogenoidea:
      Dactylogyridae).
AB  - Mastacembelocleidus gen. n. (Monogenoidea: Dactylogyridae) is proposed to include
      two species collected and redescribed from spiny eels (Mastacembelidae) in India
      and Iraq: Mastacembelocleidus bam (Tripathi, 1959) comb. n. (syn. Ancyrocephalus
      bam Tripathi, 1959) from the gills of Macrognathus pancalus (new host record) and
      Macrognathus aculeatus (Synbranchiformes: Mastacembelidae) from Lucknow, India;
      and Mastacembelocleidus heteranchorus (Kulkami, 1969) comb. n. (syn. Urocleidus
      heteranchorus Kulkarni, 1969) from the gills of Mastacembelus armatus from
      Lucknow, India, and Mastacembelus mastacembelus (new host record) from the
      environs of Erbil, Iraq (new locality record). Urocleidus rhyncobdelli Jain,
      1959, Haliotrema tandani Agrawal et Singh, 1982 and Urocleidus raipurensis Dubey,
      Gupta et Agarwal, 1992 are considered junior subjective synonyms of M. bam.

PMID- 15729941
TI  - Fish trypanosomes from the Okavango Delta, Botswana.
AB  - During 2001 and 2002, blood smears from 37 of 120 fishes belonging to 10 species
      captured in the Okavango Delta region of Botswana, were found to harbour
      trypanosomes. These trypanosomes displayed differing staining properties, were
      morphometrically variable, and ranged in total length from 29.5 to 80.8 microm.
      Mixed populations of the smaller and larger trypanosomes were found in most fish
      examined. Despite variations in size and appearance, these specimens are
      tentatively identified as Trypanosoma mukasai Hoare, 1932, likely adding another
      9 new hosts to those known for this parasite. It is possible that Trypanosoma
      clariense Pienaar, 1962, described from Clarias gariepinus in South Africa, is
      also a junior synonym of T. mukasai.

PMID- 15729942
TI  - Two new species of Myliocotyle (Monogenea: Monocotylidae) from the gills of
      Aetomylaeus maculatus and A. nichofii (Elasmobranchii: Myliobatidae) from
      Sarawak, Borneo, Malaysia.
AB  - Myliocotyle borneoensis sp. n. and M. multicrista sp. n. (Monocotylidae:
      Heterocotylinae) are described from the gills of the mottled eagle ray,
      Aetomylaeus maculatus (Gray), and the banded eagle ray A. nichofii (Bloch et
      Schneider) (Myliobatidae), respectively, collected from the northern coast of
      Malaysian Borneo. These are the first monogeneans to be described on
      elasmobranchs from Borneo. The formerly monotypic Myliocotyle (for M.
      pteromylaei) was distinguished from other monocotylids by the distribution and
      morphology of the eight sclerotised dorsal haptoral accessory structures and the
      morphology of the male copulatory organ. However, we have determined that M.
      pteromylaei has ten structures on the dorsal surface of the haptor. Myliocotyle
      borneoensis is distinguished from M. pteromylaei by the morphology of the male
      copulatory organ and its accessory piece. Myliocotyle multicrista has 12
      sclerotised dorsal haptoral accessory structures and a male copulatory organ with
      two accessory pieces. Additional sclerotised ridges across the ventral surfaces
      of each loculus (except the posterior-most pair) are also present in M.
      multicrista. The diagnosis for Myliocotyle is revised given our discovery of
      additional dorsal haptoral accessory structures in the type species and to
      accommodate other new characters of the two new species. Anterior secretions of
      Myliocotyle are discussed.

PMID- 15729943
TI  - Functional and phylogenetic components in cercarial nervous systems.
AB  - Studies involving comparisons of taxa that vary in their degree of relatedness
      may allow the distinction of functional and phylogenetic components in cercarial
      sensory systems. In this study, cercariae of allocreadiids Bunodera Railliet,
      1896 and Crepidostomum Braun, 1900, lecithodendriid Allassogonoporus Olivier,
      1938 and opecoelid Allopodocotyle Pritchard, 1966 were compared as regards
      ultrastructure and chaetotaxy of sensory receptors as well as neuromorphology.
      Cercariae were treated with acetylthiocholine iodide and silver nitrate and some
      were processed for scanning and transmission electron microscopy. The types of
      cercarial sensory receptors differed in the presence of a tegumentary sheath, a
      dome-like base and a tegumentary collar, number of cilia (0, 1, 2 or more),
      cilium length (short, moderately long or long) and tegumentary collar length (low
      to moderately low, high or very high). Chaetotaxic patterns were consistent at
      the family level in all taxa studied. Irregular cholinergic nerve networks were
      identified. The present study indicates that the major categories of cercarial
      sensory receptors are nonciliated (including sheathed and subtegumentary types)
      and ciliated (including uncollared and collared types) receptors. It also allows
      the distinction of functional and phylogenetic components in the sensory systems
      of the cercariae studied. Functional components were reflected in the numbers of
      sensory receptors associated with each nerve region and in the ultrastructure and
      site-specificity of receptor types. Phylogenetic components included taxon
      specific chaetotaxic patterns and receptor types.

PMID- 15729944
TI  - The life cycle of Paracardicoloides yamagutii Martin, 1974 (Digenea:
      Sanguinicolidae).
AB  - The sanguinicolids Paracardicoloides yamagutii Martin, 1974 and Plethorchis
      acanthus Martin, 1975 were obtained from their definitive hosts, Anguilla
      reinhardtii Steindachner and Mugil cephalus Linnaeus (respectively) in the
      tributaries of the Brisbane River, Queensland, Australia. Two putative
      sanguinicolid cercariae were collected from a hydrobiid gastropod, Posticobia
      brazieri Smith, in the same waters. The two cercariae differ markedly in size and
      the form of their sporocysts. Both putative cercariae develop in the digestive
      gland of Po. brazieri. The ITS2 rDNA region from these sanguinicolids and a
      Clinostomum species (utilised as an outgroup due to the close morphological
      similarities between the cercarial stages of the Clinostomidae and the
      Sanguinicolidae) were sequenced and aligned. Comparison of the ITS2 sequences
      showed one cercaria to be that of P. yamagutii. This is the first sanguinicolid
      life history determined by a molecular method. P. yamagutii is the fourth
      sanguinicolid known to utilise a freshwater hydrobiid gastropod as its
      intermediate host. ITS2 rDNA is effective in distinguishing sanguinicolids at the
      species level.

PMID- 15729945
TI  - Arlenelepis harpiprioni gen. et sp. n. (Cestoda: Dilepididae) from Harpiprion
      caerulescens (Vieillot) (Aves: Threskiornithidae) in Paraguay.
AB  - Arlenelepis harpiprioni gen. et sp. n. (Cyclophyllidea, Dilepididae) is described
      from the plumbeous ibis Harpiprion caerulescens (Vieillot) (Ciconiiformes,
      Threskiomithidae) in Province Concepcion, Paraguay. This cestode is characterised
      by a very small body (not exceeding 5 mm in length) consisting of about 30
      proglottides, musculo-glandular rostellar apparatus, rostellar hooks arranged in
      two regular rows, few testes (7-10 in number) situated mostly in a post-ovarian
      group but one testis pre-ovarian, a large oval cirrus sac reaching antiporal
      osmoregulatory canals, massive cirrus armed with needle-shaped and thorn-shaped
      spines, long convoluted vagina, and longitudinally elongate sacciform horseshoe
      shaped uterus with deep lobes of the medial uterine wall. The new genus is unique
      among the family Dilepididae in possessing a rhynchus armed with conical spines.

PMID- 15729946
TI  - Ultrastructure of the apical glandular region of the scolex of Proteocephalus
      torulosus (Cestoda: Proteocephalidae).
AB  - In the apical glandular region of the adult Proteocephalus torulosus (Batsch,
      1786), two types of eccrine gland cells are present. The first type of
      unicellular gland produces large electron-dense granules of various sizes. The
      second type contains small electron-dense granules. Most cells form glands with
      large granules; glands with small granules are infrequent. The secretion of both
      types of gland cells is concentrated in the apical parts of the cyton and in the
      ducts opening to the exterior. On the scolex of P. torulosus, there are regional
      structural differences of the microthrix border. The apical glandular region
      bears filamentous microtriches only. On the remaining frontal part, surrounding
      the glandular region, there are blade-like and filamentous microtriches. The
      lateral parts of the scolex and suckers bear blade-like microtriches. Possible
      functions of both types of gland cells and different parts of the scolex
      microthrix border are discussed. The unique structure of the frontal part of the
      scolex of P. torulosus and its differences from Proteocephalus macrocephalus, P.
      longicollis and P. percae correlate well with the putative basal phylogenetic
      position of P. torulosus among European species of Proteocephalus.

PMID- 15729948
TI  - New data on the morphology and systematic status of Spinitectus petrowi and
      Spinitectus gigi (Nematoda: Cystidicolidae) parasitic in catfishes in central
      China.
AB  - Two little-known nematode species of the genus Spinitectus Fourment, 1883, S.
      petrowi Belous, 1965 (prevalence 25%, intensity 1-8) and S. gigi Fujita, 1927
      (prevalence 10%, intensity 2-3), were collected from the gastrointestinal tract
      of the yellow catfish, Pelteobagrus fulvidraco (Richardson), from Liangzihu Lake,
      Hubei Province, central China, in September of 2002. The light and scanning
      electron microscopical examination of this material, supplemented by a few museum
      specimens of S. gigi collected from the catfish Clariasfuscus (Lacepede) in
      southern China, made it possible to study in detail the morphology of these
      parasite species and to redescribe them. The first species, whose correct name is
      S. petrowi Belous, 1965, exhibits some morphological features (e.g., unusually
      short vestibule, shape of pseudolabia and of the left spicule) not found in most
      other congeners; a unique feature is the presence of peculiar pairs of
      transversely oriented peg-like cuticular spines with rounded ends on the ventral
      surface of the female tail. Spinitectus gigi was found to have 28-31 cuticular
      spines in the first ring, relatively long distances between the 2nd-7th rings of
      spines, and anterior rings divided into 2 sectors; the excretory pore is located
      at the level of the 4th ring of cuticular spines; males posses 4 pairs of preanal
      and 6 pairs of postanal caudal papillae and a pair of small phasmids.
      Spinitectus bagri Wang, Wu et Yu, 1993 and S. wulingensis Yu et Wang, 1997 are
      considered junior synonyms of S. petrowi, whereas S. clariasi Ky, 1971, S.
      ophicephali Ky, 1971 and S. yuanjiangensis Wang, Wu et Yu, 1997 are regarded to
      be junior synonyms of S. gigi. Spinitectus petrowi was not previously reported
      from China.

PMID- 15729947
TI  - Redescription of Dracunculus globocephalus Mackin, 1927 (Nematoda:
      Dracunculidae), a parasite of the snapping turtle, Chelydra serpentina.
AB  - Dracunculus globocephalus Mackin, 1927 (Nematoda: Dracunculoidea) is redescribed
      from specimens collected from the mesentery of the snapping turtle, Chelydra
      serpentina (L.), in Louisiana, USA. The use of scanning electron microscopy,
      applied for the first time in this species, made it possible to study details in
      the structure of the cephalic end and the arrangement of male caudal papillae
      that are difficult to observe under the light microscope. This species markedly
      differs from all other species of Dracunculus in having the spicules greatly
      unequal in size and shape, in the absence of a gubernaculum, and in the
      disposition of male caudal papillae. The validity of D. globocephalus is
      confirmed, but the above mentioned morphological differences are not sufficient
      for listing it in a separate genus. This is the first record of D. globocephalus
      in Louisiana.

PMID- 15729949
TI  - Chigger mites of the genus Eutrombicula ewing, 1938 (Acari: Trombiculidae) from
      Cuba, with the description of three new species.
AB  - Three new species of chigger mites, Eutrombicula cubensis sp. n. and E.
      anguliscuta sp. n. from lizards and bats, and E. leiocephali sp. n. from lizards,
      are described. One species, E. lipovskyana (Wolfenbarger, 1953), is recorded for
      the first time in Cuba. Data on distribution of E. alfreddugesi (Oudemans, 1910)
      in Cuba are reported.

PMID- 15729950
TI  - Effect of tick salivary gland extract on the cytokine production by mouse
      epidermal cells.
AB  - Previous studies have demonstrated that both tick saliva and Borrelia burgdorferi
      sensu lato antigens modulate the cytokine response of the host. In this paper,
      the effect of salivary gland extract (SGE) from Ixodes ricinus (L., 1758) ticks
      on cytokine production by primary cultures of mouse epidermal cells stimulated
      with Borrelia afzelii Canica, Nato, du Merle, Mazie, Baranton et Postic, 1993
      spirochetes was analysed. Epidermal cells were derived from C3H/HeN mice,
      susceptible to Lyme disease, and BALB/c mice, which are resistant. In cultures
      from C3H/HeN mice, SGE down regulated production of tumour necrosis factor alpha
      (TNF-alpha) and up regulated Th2 cytokine, interleukin 4 (IL-4). Cultures from
      BALB/c mice produced higher basal levels of monitored cytokines, but their
      production was affected by SGE a different way. While Th2 cytokines IL-6 and IL
      10 were down regulated, the effect on TNF-alpha and IL-4 was ambiguous. These
      results indicate that the effect of tick saliva on the epidermal cells of Lyme
      disease-susceptible C3H/HeN mice mirrors its effect on other cells of the immune
      system.

PMID- 15729951
TI  - Failed attempt of Cryptosporidium andersoni infection in lambs.
AB  - Four lambs 4 months old were inoculated with Cryptosporidium andersoni oocysts
      (bovine isolate) in a dose of 5 x 10(6) per animal followed later by 1 x 10(7)
      oocysts per animal. No animal shed Cryptosporidium oocysts during 56 days post
      infection, no lamb showed clinical symptoms of cryptosporidiosis and no
      macroscopic changes were detected in the abomasum immediately after autopsy.
      Histological examinations did not demonstrate the occurrence of Cryptosporidium
      in the abomasum and other selected organs.

PMID- 15729952
TI  - Economic evaluation of medical technologies.
AB  - Innovation in medical science is progressing at a rapid pace. As a result, new
      medical technologies that offer to improve upon or completely replace existing
      alternatives are continually appearing. These technologies--which include
      pharmaceuticals, devices, equipment, supplies, medical and surgical procedures,
      and administrative and support systems--are changing the way medicine can be
      practiced and delivered, forcing healthcare providers and policymakers to
      consistently evaluate and adapt to new treatment options. Meanwhile, society is
      becoming more demanding of new medical technologies. Emerging medical technology,
      however, has been viewed as a significant factor in increasing the cost of
      healthcare. The abundance of new medical alternatives, combined with scarcity of
      resources, has led to priority setting, rationing and the need for more
      technology management and assessment. Economic evaluation of medical technologies
      is a system of analysis used to formally compare the costs and consequences of
      alternative healthcare interventions. EEMT can be used by many healthcare
      entities, including national policymakers, manufacturers, payers and providers,
      as a tool to aid in resource allocation decisions. This paper discusses the four
      current popular methodologies for EEMT (cost-minimization, cost-benefit, cost
      effectiveness and cost-utility), and describes the industry environment that has
      shaped their development.

PMID- 15729953
TI  - Implications of endometriosis for women who observe Jewish law (halakha).
AB  - Endometriosis is a chronic disease characterized by ectopic deposits of
      endometrial glands and stroma located outside the uterus. Women with symptomatic
      endometriosis may experience premenstrual bleeding or staining, pain and other
      physical sensations, as well as other symptoms dependent upon the stage and
      location of the endometrial implants. We discuss the particular implications of
      these symptoms for women who observe the part of Jewish law known as hilkhot
      niddah. The laws of niddah, also known as taharat hamishpahah (family purity),
      dictate the timing of the physical relationship between a married couple. These
      laws proscribe any physical contact between the couple during the time that the
      wife has the status of niddah. This status is obtained by any uterine bleeding
      that is not caused by injury. Menstruation is the most common cause of the niddah
      status, but niddah and menstruation are not synonymous. Since, to the best of our
      knowledge, there is no written discussion of the specific implications of
      endometriosis for this population, we discuss the relevant halakhic and medical
      literature and hope that such analysis will facilitate efforts to assist the
      observant couple in gaining regular niddah-free segments of time.

PMID- 15729954
TI  - Clinical experience with repaglinide in patients with non-insulin-dependent
      diabetes mellitus.
AB  - BACKGROUND: Repaglinide, a new insulin secretagogue, is purported to be as
      effective as sulphonylurea but is less hypoglycemic-prone. OBJECTIVES: To assess
      the efficacy of repaglinide and its proclivity for hypoglycemia in a post
      marketing study. METHODS: The study group comprised 688 patients, aged 26-95
      years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The
      patients were divided into three groups based on previous therapy: a)
      sulphonylurea-treated (group 1, n = 132); b) metformin with or without
      sulphonylurea where sulphonylurea was replaced with repaglinide (group 2, n =
      302); and c) lifestyle modification alone (drug-naive) (group 3, n = 254). At
      initiation of the study, all patients were transferred from their current
      treatment to repaglinide. Only patients in group 2, with combined sulphonylurea
      plus metformin, continued with metformin plus repaglinide. Fasting blood sugar,
      hemoglobin A1c and weight were measured at study entry and 4-8 weeks following
      repaglinide therapy. A questionnaire documented the number of meals daily and the
      presence of eating from fear of hypoglycemia. RESULTS: The fasting blood sugar
      level of the entire cohort dropped from 191 +/- 2.4 to 155 +/- 2.0 mg/dl (P <
      0.0001); HbA1c from 8.8 +/- 0.1 to 7.7 +/- 0.1% (P < 0.0001). The drop of HbA1c
      in groups 1, 2 and 3 respectively were: 1.04 +/- 0.22% (P < 0.0001), 1.14 +/-
      0.24% (P < 0.0001), and 1.51 +/- 0.31% (P = 0.0137). Weight dropped from 81 +/-
      0.7 to 80.2 +/- 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from
      157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 +/- 0.4 to
      2.4 +/- 0.4 (P < 0.001). No serious adverse reactions occurred during the study.
      CONCLUSIONS: Repaglinide is an effective oral hypoglycemic agent taken either as
      monotherapy or combination therapy. There is less eating to avoid hypoglycemia,
      fewer meals consumed, and weight loss.

PMID- 15729955
TI  - Effect of non-steroidal anti-inflammatory drugs on natural killer cell activity
      in patients with dementia.
AB  - BACKGROUND: Alteration of innate and acquired immunity can play a role in the
      mechanism involved in the development of dementia. Epidemiologic studies indicate
      that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow
      progression of Alzheimer disease. OBJECTIVES: To determine whether the use of
      NSAIDs is associated with natural killer activity alteration in AD and multi
      infarct vascular dementia patients, as compared with non-demented elderly and
      healthy young people. METHODS: In this prospective open study four groups of
      subjects (AD, VD, non-demented elderly, and healthy young people) were treated
      with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7
      days. Natural killer cell cytotoxicity was measured after flow cytometry analysis
      before and after treatment. RESULTS: Of the 49 subjects studied, 15 had a
      diagnosis of AD (3 men, 12 women; mean age 83.5 +/- 8.1 years), 15 had a
      diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 +/- 8.4), 13 were
      non-demented elderly (1 man, 12 women; mean age 80.2 +/- 7.2), and 6 were healthy
      young volunteers (3 men, 3 women; mean age 36.8 +/- 4.4). While all examined
      subjects showed decreased NK cell cytotoxicity after treatment, this decrease was
      most prominent and statistically significant in elderly patients suffering from
      vascular dementia--from an average of 30.5 +/- 11.8% before treatment to 22.5 +/-
      16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only
      moderate and not statistically significant in all other elderly and young
      subjects. Young healthy volunteers exhibited a significantly higher total NK
      cytotoxicity before and after treatment compared to all age groups (P < 0.001).
      CONCLUSION: These findings suggest that NSAIDs decrease NK activity in vascular
      dementia patients. Our findings also suggest that natural killer activity
      alteration cannot explain the ability of anti-inflammatory drugs to delay the
      onset or slow the progression of AD.

PMID- 15729956
TI  - Surgical treatment and long-term outcome of patients with familial adenomatous
      polyposis: 16 years experience at the Tel Aviv Sourasky Medical Center.
AB  - BACKGROUND: Restorative proctocolectomy eliminates the risk of colorectal cancer
      in patients with familial adenomatous polyposis. Complications and extra
      intestinal manifestations are inherent to the procedure. OBJECTIVES: To evaluate
      operative procedures, complications, early and late results and long-term
      functional outcome in FAP patients operated in our department. METHODS: The study
      group included all patients with FAP who were operated between 1988 and 2003.
      Demographic data, length of follow-up, complications, colorectal cancer, pouch
      function and extracolonic manifestations were recorded. RESULTS: Median age at
      surgery was 33 years (range 13-61 years). The final operative breakdown was: 48
      proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock's pouch, 5 permanent
      ileostomies, and 2 colectomies with ileorectal anastomosis. There was no
      perioperative mortality. Early and late complications occurred in 20 and 9
      patients, respectively. Twelve patients required reoperation. Colorectal
      carcinoma was diagnosed in eight patients, three of whom were in an advanced
      stage. The mean follow-up was 74 months (range 3-288 months). Four patients were
      lost to follow-up. Extracolonic manifestations developed in 38 patients,
      including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in
      5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid
      tumor and malignant fibrous histiocytoma. At last follow-up, 37 IPAA patients
      have (median) six bowel movements/24 hours and good fecal control. CONCLUSIONS:
      Restorative proctocolectomy can be performed with low mortality, acceptable
      morbidity, and good functional results. Patients should be closely followed after
      surgery for development of other manifestations of the syndrome. Relatives of the
      affected patients should be referred to a specialist multidisciplinary clinic.

PMID- 15729957
TI  - The effect of the Dead Sea environment on uveitis.
AB  - BACKGROUND: Uveitis is an acute or chronic inflammatory process of the uvea
      caused by a number of etiologies. In many patients the etiology is unknown.
      OBJECTIVE: To investigate the effect of the Dead Sea environment (climatotherapy)
      on the signs, symptoms and clinical course of chronic uveitis. METHODS: Fifty
      five patients with chronic uveitis were examined at the beginning and end of a 3
      4 week stay at the Dead Sea region and on repeat visits to the region. Study data
      included demographic information, medical history, etiology, diagnosis,
      medication, and a complete ophthalmic examination. RESULTS: Statistically
      significant improvements were seen between the two examinations within each visit
      in four parameters (negative values indicate improvement): a) visual acuity for
      near and far: Jaeger (-0.98 +/- 0.18, P < or = 0.001) and best corrected visual
      acuity (-0.22 +/- 0.04, P < or = 0.0001); b) anterior chamber flare (-0.18 +/-
      0.06, P < or = 0.01); c) anterior chamber cells (-0.12 +/- 0.03, P < or =
      0.0001); and d) vitreous cells (-0.17 +/- 0.05, P < or = 0.001). There was a
      significant mean improvement during visits to the Dead Sea area and a slight
      dissipation of the effect during the intervals between visits. Sixty-four percent
      of the patients reported that they required less medication and had fewer and
      milder attacks of uveitis following the visits. CONCLUSIONS: The results of this
      study provide evidence of short- and possibly long-term improvement in the signs
      and symptoms of uveitis following exposure to the Dead Sea environment.

PMID- 15729958
TI  - Salmonellosis: an epidemiologic study.
AB  - BACKGROUND: Salmonella species commonly produce acute gastroenteritis. The
      clinical course may be affected by factors such as age, immunosuppression, and
      underlying disorders. OBJECTIVES: To investigate clinical and laboratory
      differences in the infected population and the risk of complications according to
      the different age groups. METHODS: The records of 295 patients with positive
      cultures for Salmonella were divided into six age groups and reviewed
      retrospectively for the years 1994-1997. Demographic, clinical and laboratory
      data, extraintestinal manifestations, underlying disorders, organism source, and
      susceptibilty to antibiotics were analyzed. RESULTS: We found that 88.5% were
      only stool positive, 9.2% had positive blood cultures, and 2.4% were positive in
      both blood and stool; 3.6% were found to have underlying disorders. Anemia,
      disturbed liver function tests and hypoalbuminemia were the most common
      pathologic laboratory findings. Salmonella serogroups B and D were isolated most
      frequently. The rate of positive blood cultures increased significantly during
      the years, as did resistance to ampicillin and trimethoprimsulfamethoxazole.
      Salmonella infection has two peaks of incidence: at ages 1-5 and 15-65 years.
      Bacteremia was prominent in the extreme ages. CONCLUSIONS: Salmonella infection
      has a different clinical presentation in different age groups. The significant
      increase in the rate of bacteremia in the extreme age groups necessitates a
      different attitude and management for these heterogeneous patient populations.

PMID- 15729959
TI  - Pregnancies and outcome in women with cystic fibrosis.
AB  - BACKGROUND: Along with the increased life expectancy in cystic fibrosis and the
      remarkable progress in its management and therapy, issues of female fertility and
      pregnancy are frequently raised. These include infertility, severity of lung
      disease, pancreatic insufficiency, poor nutritional status, glucose intolerance
      and diabetes, drug safety, and long-term maternal and neonatal outcome.
      OBJECTIVE: To describe the experience of our CF center in the management of CF
      pregnant woman from 1977 to 2004. METHODS: We analyzed 27 years of records (1977
      2004) of the national CF registry of all CF women who wished to conceive and
      became pregnant. RESULTS: Eight CF women (mean age 24 +/- 4.5 years) who wished
      to conceive had 11 pregnancies and delivered 12 neonates. The pregestational
      results of forced expiratory volume per 1 second varied significantly among
      patients (59 +/- 23%), yet most (10/11) stayed stable throughout the pregnancy
      course. Maternal deterioration in CF condition occurred in only one mother,
      necessitating cesarean section. In 9 of the 11 pregnancies the women were
      pancreatic-insufficient. Of the 11 pregnancies, 2 CF women had diabetes mellitus
      and 3 developed gestational diabetes. One pregnancy occurred in a mother with a
      transplanted lung. Of the 12 neonates, 3 were preterm and one was born with
      esophageal atresia. No miscarriages, terminations or neonatal mortalities
      occurred. Although most of the CF mothers had FEV1 below 55% before pregnancy,
      the maternal and neonatal outcome was favorable and lung function tests generally
      remained stable. CONCLUSIONS: We conclude that pregnancy in CF is feasible with a
      positive maternal and neonatal outcome. Early participation of the CF physician
      in the wish of the CF woman to reproduce is required. The integration of an
      intensive multidisciplinary approach during pregnancy, which includes close
      follow-up of maternal and fetal condition by the various specialists, should
      ensure an optimal outcome.

PMID- 15729960
TI  - Advanced maternal age and prenatal diagnosis: it's time for individual assessment
      of genetic risks.

PMID- 15729961
TI  - Retropubic radical prostatectomy: associated blood loss and transfusion
      requirements--a two-decade perspective review.
AB  - Bleeding during retropubic radical prostatectomy arises from venous structures in
      the majority of cases. Since its introduction two decades ago, the nerve-sparing
      procedure with surgical control of the dorsal venous complex has led to a
      reduction in blood loss and blood transfusion rate. The reducton in blood loss is
      a result of better understanding of the prostatic blood vessel anatomy, extensive
      surgical experience over time, and reduction in transfusion triggers with an
      acceptance of lower postoperative hemoglobin values. Increased blood loss during
      RRP is associated with poorer outcomes most probably due to surgical
      difficulties. But as for now, there are no decisive risk factors for clinically
      significant bleeding during RRP although newer technologies for hemostasis of the
      dorsal vein complex are being utilized.

PMID- 15729962
TI  - Endometriosis: halakhic aspects as indications for treatment.

PMID- 15729963
TI  - Seeing better at the Dead Sea.

PMID- 15729964
TI  - Advanced maternal age is no longer so advanced.

PMID- 15729965
TI  - Efficacy of intravenous albumin administration in hypoalbuminemic patients: why
      and when.

PMID- 15729966
TI  - The use of albumin in patients with decompensated cirrhosis: the case in favor.
AB  - In conclusion, in the course of patients with advanced liver disease there are
      several indications for institution of intravenous albumin. These include: a)
      enhancement of diuretic effect on mobilization of ascites fluid, b) prevention of
      post-paracentesis circulatory dysfunction after total/large volume paracentesis,
      c) prevention of hepatorenal syndrome in patients affected with SBP, and d)
      administration of albumin in combination with vasoconstrictor drugs as the only
      effective therapy for hepatorenal syndrome. Albumin is relatively inexpensive and
      can be given in an outpatient setting.

PMID- 15729967
TI  - The use of albumin in all patients with decompensated cirrhosis is not justified.

PMID- 15729968
TI  - Retroareolar leiomyoma of the male breast.

PMID- 15729970
TI  - Cervico-facial emphysema and pneumomediastinum complicating a high-speed drill
      dental procedure.

PMID- 15729969
TI  - Persistent plastic bronchitis in a child after cardiac surgery.

PMID- 15729971
TI  - Hyponatremia as a presenting sign of a pituitary intrasellar cyst.

PMID- 15729972
TI  - Leave the old pacemaker in?

PMID- 15729973
TI  - Hyperglycemia and acute ischemic stroke.

PMID- 15729974
TI  - Procedural sedation.

PMID- 15729975
TI  - Fibromyalgia: ten hot questions and comments.

PMID- 15729976
TI  - Systemic scleroderma and Addison's disease.

PMID- 15729977
TI  - [Trends in mortality from ischemic heart disease and acute myocardial infarction
      in Costa Rica, 1970-2001].
AB  - OBJECTIVE: To describe epidemiologic trends in mortality from cardiovascular
      diseases (CVD), ischemic heart disease (IHD), and acute myocardial infarction
      (AMI) in Costa Rica, by sex and geographic region, between 1970 and 2001.
      METHODS: We performed a descriptive study of mortality from CVD, IHD, and AMI in
      Costa Rica between 1970 and 2001. Information was obtained from the Central
      American Population Center's database. Mortality data for IHD and AMI between
      1970 and 2001 were analyzed in accordance with the latest revision of the
      International Classification of Diseases (ICD). Costa Rica's territory was
      divided into the following regions: the metropolitan area (8 cantons), the semi
      urban area of Valle Central (18 cantons), the rural area of Valle Central (17
      cantons), the semi-urban lowlands (12 cantons), and the rural lowlands (26
      cantons). Mortality trends by quinquennia (between 1970 and 1999) and for the
      2000-2001 biennium were examined in the form of crude mortality rates per 100 000
      inhabitants for each cause or group of causes, by age, sex, and year of death.
      All rates were adjusted for sex, age, year of death, and geographic region
      through the direct method of standardization, using the population of Latin
      America in 1960 as the standard population. RESULTS: Mortality from CVD dropped
      by an average of 33% (46.6% among women and 20.2% among men), while mortality
      from IHD rose by an average of 18.4% (6.1% among women and 28.4% among men). The
      adjusted mortality rate for AMI among men rose by 12.8% over the study period and
      dropped slightly by 4.4% among women. Mortality from CVD, IHD, and AMI was
      greater in men than in women during the entire study period. Mortality rates for
      IHD and AMI rose in semi-urban and urban areas, especially in the rural lowlands,
      where they increased with respect to the 1995-1999 rates by 123.9% and 76.9%,
      respectively. CONCLUSIONS: A reduction in mortality from CVD was noted. The
      largest rates were seen among men and in persons 75 years of age or older. The
      largest increases in mortality rates from IHD and AMI were seen in semi-urban and
      rural areas, among men, and in persons 75 years of age or older. Special
      attention should be paid to risk factors for CVD, such as smoking, arterial
      hypertension, overweight and obesity, sedentary habits, and an unhealthy diet.

PMID- 15729978
TI  - CD4 cell counts in adults with newly diagnosed HIV infection in Barbados.
AB  - OBJECTIVE: To evaluate the absolute CD4 cell counts of all the newly diagnosed
      HIV-infected persons who presented at the Ladymeade Reference Unit (LRU), which
      serves as the national HIV/AIDS referral and treatment center for the country of
      Barbados. DESIGN AND METHODS: The study group was comprised of HIV-infected
      adults who had been diagnosed with HIV infection and referred to the LRU between
      January and December 2002. All the patients referred to the LRU had a CD4 cell
      count done at their first visit to the unit, as part of the routine workup to
      assess their disease status and need for antiretroviral therapy. RESULTS: Of the
      106 newly diagnosed adults, 62 of them (58.5%) were males, who had a median age
      at presentation of 40 years; the other 44 of them (41.5%) were females, and their
      median age at presentation was 36 years. Nearly one-fifth (18.2%) of the females
      were aged 16-25 years, whereas only 8.1% of the males were in this age group. The
      majority (57.6%) of the study group were diagnosed because they presented with an
      HIV/AIDS-related illness. Overall, the median CD4 cell count at the time of
      diagnosis was 183/microL; 52 of 103 adults (50.5%) with a newly diagnosed HIV
      infection had a CD4 cell count that was < 200. Among males, the median CD4 cell
      count was 161/microL, and 32 (53.3%) of 60 males had CD4 cell counts < 200. In
      contrast, among females, the median CD4 cell count was 223, and 20 (46.5%) of 43
      females had a CD4 cell count that was < 200/microL. However, this difference in
      the proportion of males and females with a CD4 cell count less than 200/microL
      was not statistically significant (P = 0.63). CONCLUSIONS: At the time of HIV
      diagnosis, over one-half of the adults had an initial CD4 cell count that was
      consistent with relatively advanced disease. Proportionally more women than men
      presented at a younger age, and proportionally more women than men presented in
      the early stages of the disease. These patterns indicate a clear need for
      enhanced educational efforts regarding the importance of HIV testing for at-risk
      individuals across Barbados. This testing could improve efforts to reduce
      transmission as well as the prognosis for patients who receive antiretroviral
      therapy.

PMID- 15729979
TI  - [Epidemiology of overweight and obesity and its determinants in Belo Horizonte
      (MG), Brazil: a cross-sectional population-based study].
AB  - OBJECTIVE: To determine the prevalence of overweight and obesity and to study
      potential risk factors for these conditions in persons over 18 years of age in
      the metropolitan area of Belo Horizonte, Brazil. METHODS: Data were obtained from
      a population-based study conducted in 1996 and 1997 by the Brazilian Institute of
      Geography and Statistics (Instituto Brasileiro de Geografia e Estatistica, IBGE)
      with a random sample of 1 105 individuals. Height and weight were measured by
      trained personnel. Overweight (body mass index [BMI] > or = 25.0 kg/m2) and
      obesity (BMI > or = 30.0 kg/m2) were the dependent variables. Bivariate analysis
      and multivariate logistic regression were used to identify potential risk factors
      for overweight and obesity. RESULTS: The prevalence of overweight and obesity was
      31.1% (95% confidence interval 195% CI]: 27.3 to 35.2) and 5.7% (95% CI: 4.0 to
      8.1), respectively, in men, and 25.9% (95% CI: 22.4 to 29.8) and 14.7% (95% CI:
      11.9 to 17.9), respectively, in women. Multivariate analysis revealed that age
      and marital status were independent risk factors for overweight, whereas age,
      sex, and education were independent risk factors for obesity. Being female and
      well-educated showed a protective effect against overweight (odds ratio [OR] =
      0.52; 95% CI: 0.33 to 0.83), but not against obesity (OR = 3.01; IC 95%: 1.14 to
      7.94). Women with low education had a significantly greater risk (OR = 5.95;
      95%CI: 2.51 to 14.12) of developing obesity than men having a high educational
      level. CONCLUSIONS: These results suggest that overweight and obesity may be
      serious public health problems in the metropolitan area of Belo Horizonte,
      Brazil. It is important to carry out further studies in order to explore the
      potential relationship between overweight and obesity on the one hand, and
      behavioral variables, such as smoking and alcohol consumption, on the other.

PMID- 15729980
TI  - [Azlocillin plus amikacin: an alternative therapy for sepsis caused by resistant
      staphylococci?].
AB  - OBJECTIVE: To assess the effectiveness of combined therapy with azlocillin and
      amikacin in a group of neonates with sepsis caused by multiresistant
      staphylococci who were hospitalized in the neonatal intensive care unit of
      Hospital Ginecobstetrico "America Arias" in Havana, Cuba, from 1998 to 2000.
      METHODS: A retrospective study was carried out of the clinical and laboratory
      results obtained in 15 patients with sepsis caused by multiresistant
      staphylococci who received combined therapy with azlocillin and amikacin,
      according to hospital guidelines on the use of antibiotics. We used a broth
      microdilution method to study the patterns of resistance shown by isolated
      strains to 10 of the antibiotics in use. In vitro synergy tests, specifically the
      checkerboard technique with microtitration plates, were used to observe the
      effects of treatment in 8 patients. RESULTS: Twelve coagulase-negative
      staphylococci and three Staphylococcus aureus isolates showed five different
      patterns of resistance on the basis of their sensitivity to oxacillin, three
      aminoglycosides, and vancomycin. Six of the synergy tests showed a considerable
      synergistic effect, with an average three-fold reduction in the minimum
      inhibitory concentrations (MIC) of the two antibiotics used to treat the
      patients. No antagonistic effects were noted, and the combined antibiotics showed
      an overall clinical effectiveness of 91.7%. CONCLUSIONS: The test showed that the
      therapeutic combination used was effective, but further studies are needed before
      conclusive results are obtained.

PMID- 15729981
TI  - A nationwide population screening program for diabetes in Brazil.
AB  - OBJECTIVES: In 2001, persons throughout Brazil who were 40 years old or older
      were invited to participate in community screening for diabetes as part of the
      Brazilian Ministry of Health's Plan for the Reorganization of Care for Arterial
      Hypertension and Diabetes Mellitus. This report describes the overall
      participation rate and positivity rate of the screening campaign, as well as
      factors associated with the level of participation among the municipalities in
      Brazil. METHODS: Screening test positivity was defined as a fasting glucose of >
      or = 100 mg/dL or a casual glucose of > or = 140 mg/dL. Screening data were
      obtained from the Ministry of Health and were analyzed for each municipality.
      RESULTS: Out of the 5 561 municipalities in Brazil, 5 301 of them (95.3%)
      participated and reported results. Of the 30.2 million persons in the target
      population, 22.1 million of them (73.0%) were tested, and 3.5 million of the
      persons tested (15.7%) were positive. Higher odds of a high population
      participation rate (> or = 80%) were seen in municipalities that were of small
      size (risk ratio (RR) = 5.0, comparing extremes), were located in the North
      region of the country (RR = 1.8), were located outside of a metropolitan region
      (RR = 1.4), and had a higher proportion of their population who had completed
      elementary school (RR = 1.2) (P < 0.05). There was a parallel increase in glucose
      testing nationwide during and immediately after the campaign, presumably in part
      for diagnostic confirmation of cases identified during screening. CONCLUSIONS:
      The massive response to the campaign attests to the potential that this type of
      program has to raise diabetes awareness and to set the stage for capacity
      building at the primary care level.

PMID- 15729982
TI  - Cancer among indigenous people in the Amazon Basin of Ecuador, 1985-2000.
AB  - OBJECTIVE: To provide some of the first data on cancer incidence among indigenous
      people in the Amazon basin of Ecuador, and to compare that incidence with the
      level found among nonindigenous persons living in that same area. METHODS: From
      the study area 1 207 cancer cases were reported to the National Cancer Registry
      over the 1985-2000 period. Frequency and relative risks were calculated for the
      indigenous residents and for the nonindigenous residents of the area. RESULTS:
      Cancer of the testes and leukemia were the most common cancer types among
      indigenous men, and cancer of the cervix uteri was the most common among
      indigenous women. Indigenous men were at significantly lower risk for cancer of
      the stomach, skin, prostate, and lymph nodes and for leukemia than were
      nonindigenous men. Indigenous women were at significantly lower risk for cancer
      of the stomach, skin, breast, cervix uteri, and lymph nodes than were
      nonindigenous women. CONCLUSION: Our data from the Ecuadorian Amazon indicate the
      need to develop appropriate mechanisms to register the indigenous population in
      the national census as well as in the National Cancer Registry. Also needed are
      cancer early detection programs, more health education efforts, and stronger
      health services that are adapted to the local conditions. Future research should
      focus on factors that may help to explain the different cancer patterns found
      among indigenous persons and nonindigenous persons.

PMID- 15729983
TI  - [Dental caries in schoolchildren from rural communities in Itauna (MG), Brazil].
AB  - OBJECTIVE: To study the prevalence of dental caries and its association with
      socioeconomic variables among schoolchildren living in rural communities in
      Itauna, state of Minas Gerais, Brasil, in 2002. METHODS: An epidemiological
      survey was carried out among 476 schoolchildren between 4 and 15 years of age.
      The children underwent a dental examination that was performed by a single
      researcher following the methodology recommended by the World Health
      Organization. Socioeconomic data (family income, parents' education and
      occupation, household source of drinking water, and the child's sex and age) were
      gathered through an interview with the parents. RESULTS: Over three fourths of
      the parents earned no more than 360 reais (R$) (approximately US$ 153) a month
      and reported having 4 years of schooling at most. Considering both the deciduous
      and permanent dentitions, 17.86% of the children were free of caries. The mean
      number of permanent teeth that were decayed, missing or filled, and of primary
      teeth that were filled or decayed and needed extraction, was 0.94 (+/- 1.55) and
      4.00 (+/- 3,46), respectively. Multivariate analysis showed that among seven- and
      eight-year-old children whose monthly family income was above R$ 280, the risk of
      having caries in the primary (deciduous) dentition and in both dentitions was
      2.602 (95% CI: 1.004 to 6.745) and 2.854 (95% CI: 1.044 and 7.799) times greater,
      respectively, than among children from lower-income families. Seven- and eight
      year-old children whose mothers had completed at least 3 years of elementary
      school showed more than twice the risk [2.813 (95%CI: 1.221 to 6.480)] of having
      caries in the permanent dentition than children whose mothers had less schooling.
      CONCLUSIONS: In view of these results, particularly those pertaining to the
      primary dentition, there is an urgent need to implement community dental health
      strategies targeting young children in Brasil. The results suggest that in
      underprivileged populations, such as the inhabitants of rural communities in
      Itauna, families with somewhat higher incomes and better schooling are more
      likely to adopt behaviors that lead to dental caries.

PMID- 15729984
TI  - [Morphologic identification of Ehrlichia sp. in the platelets of patients
      infected with the human immunodeficiency virus in Venezuela].
AB  - OBJECTIVE: To determine the frequency of infection by bacteria of the genus
      Ehrlichia in a population of patients infected with the human immunodeficiency
      virus (HIV). As is widely recognized, HIV infection is usually followed by the
      acquired immunodeficiency syndrome (AIDS) after a variable period during which
      the individual can develop different types of opportunistic infections whose
      severity depends on his/her immune status. Human ehrlichiosis is a newly
      recognized tick-borne infectious disease caused by Ehrlichia spp., which are
      obligate intracellular, Gram-negative bacteria showing tropism for blood cells
      (leukocytes and platelets). In Venezuela, the disease was first recognized in
      humans in 1994, when intra-cytoplasmic microcolonies (morula) were found in human
      platelets. METHODS: We collected peripheral blood samples from 87 HIV-positive
      persons that were received at the Immunology Laboratory of the Oncology and
      Hematology Institute in Caracas, Venezuela, one of the country's referral centers
      for cases of HIV infection. Slides prepared from buffy coat that had been stained
      with Wright's solution and sealed with resin for preservation were examined
      retrospectively under the light microscope. RESULTS: Ehrlichia spp. were found in
      the platelets of 12 of the 87 (13.8%) patients whose slides were examined.
      CONCLUSION: The presence of Ehrlichia sp. in the platelets of HIV-positive
      patients suggests that ehrlichiosis should be among the differential diagnoses of
      opportunistic infection in this group of patients.

PMID- 15729985
TI  - Dialysis in Barbados: the cost of hemodialysis provision at the Queen Elizabeth
      Hospital.
AB  - OBJECTIVE: The purpose of this study was to assess the health service cost of
      hemodialysis delivered at the Queen Elizabeth Hospital in St. Michael, Barbados.
      METHODS: A cost analysis was performed from the viewpoint of the tertiary
      hospital studied here, using treatment protocols based on current practice for
      establishing vascular access sites (surgical set-up) and dialysis maintenance.
      Cost and patient data were collected for the period from 1 April 1998 to 31 March
      1999. Sixty-four patients were studied and a total of 7 488 hemodialysis sessions
      were performed in the study period. The costs analyzed were personnel, drug
      expenditure, supplies (dialysis and nondialysis), inpatient costs, laboratory and
      other ancillary services, and indirect or overhead costs such as engineering,
      housekeeping, laundry and administration. RESULTS: The cost per hemodialysis
      treatment was calculated as US$ 156.64 in the first year and US$ 145.55 in
      subsequent years. The total cost per patient per year was US$ 18 327.22 in the
      first year of dialysis including surgical set-up, and US$ 17 029.54 thereafter.
      Direct costs (determined by patients' utilization of resources and labor costs
      for physicians and nurses) contributed to 80.7% of the total cost. The main
      expenditures were dialysis-related supplies, labor and overheads. CONCLUSION:
      These findings are important in the light of limited economic resources available
      to health services in Caribbean countries coupled with the spiraling prevalence
      of kidney failure in these countries. Further analyses are recommended to review
      the provision of renal replacement therapy services in Barbados and to develop
      plans to expand and optimize services.

PMID- 15729986
TI  - Current strategy for leprosy control in Brazil: time to pursue alternative
      preventive strategies?

PMID- 15729987
TI  - [Rubella and congenital rubella syndrome in the Americas].

PMID- 15729988
TI  - The art and science of peace and quiet.

PMID- 15729989
TI  - Tilting at the windmill.

PMID- 15729990
TI  - PLICO.

PMID- 15729991
TI  - Essentials of hospice: what every Oklahoma physician needs to know, Part II.
AB  - Every physician, regardless of specialty, must advocate and facilitate patient
      access to comprehensive palliative and hospice care as their patients enter the
      last phase of life due to advanced disease or a terminal condition. Accordingly,
      physicians must become familiar with both the general and the disease-specific
      eligibility guidelines for hospice, the different levels of hospice care,
      physician re-imbursement for hospice patient care, and become knowledgeable in
      advance health care planning. The latter includes an understanding of Oklahoma's
      DNR law and the Advance Directive for Health Care (Living Will) law. Physician
      proficiency in the palliation of pain and non-pain symptoms that occur in
      patients at end-of-life is critical to alleviate patient suffering and to ensure
      the patient's peaceful dying.

PMID- 15729992
TI  - The ethics and economics of consuming Canadian drugs.
AB  - Many U.S. citizens are unable to afford prescription medication in their own
      country, so they purchase them from Canadian pharmacies. This paper examines the
      ethics of importing drugs from Canada, including economic implications and how
      physicians should respond to this dilemma. The four basic principles of ethics
      are balanced by examining financial incentives, current Canadian and U.S. law,
      safety issues, the burden of research and development, the impact on Canadian
      physicians, and issues of liability. The paper concludes that the principle of
      autonomy permits individuals to cross the border and purchase drugs for personal
      use; however, nonmaleficence prohibits the purchase of these drugs through third
      parties. In addition, the U.S. government has special obligations to justice and
      beneficence and may not ethically sponsor the importation of Canadian drugs.
      Finally, the paper shows that U.S. doctors must not recommend importation on the
      basis of beneficence and autonomy.

PMID- 15729993
TI  - New coding and billing opportunities for 2005--Part I.
AB  - Part I of this series will highlight several changes in coding and billing for
      2005. Medicare has established new preventive medicine services and screening
      tests for beneficiaries, but they have certain qualifications and documentation
      rules that must be followed. New codes have been established for using the
      Internet or similar electronic communications in response to a patient's request.
      There are additional revisions for pediatricians, orthopedists, endoscopists and
      surgeons performing transplants and bariatric surgery. All new CPT codes must be
      activated and deleted codes must be discontinued effective January 1, 2005. From
      that date forward, the patient's date of service must reflect current diagnosis
      (ICD-9) and procedure/services (CPT and HCPCS) codes. The Health Insurance
      Portability and Accountability Act (HIPAA) mandated a January 1, 2005, date
      compliance for all new and deleted diagnosis (ICD-9-CM) and physician service
      codes (CPT and HCPCS). Physicians no longer are allowed the 90-day grace period
      to update their coding systems to reflect the changes. The new 2005 CPT book
      contains many revisions within the codes themselves along with revisions found in
      the specific "guidelines" at the beginning of many sections. The CPT codes for
      2005 contain 26 deleted codes and 130 new codes, thus providing a challenge to
      update all coding systems by the January 1, 2005, compliance date for CPT codes.

PMID- 15729994
TI  - Advanced diagnostic centre developed.
AB  - This article describes a highly specialised diagnostic centre built on a major
      acute hospital site, the Christie Cancer Hospital, Greater Manchester. Advanced
      diagnostics, radio pharmaceuticals manufacturing and associated research and
      patient areas are in a new innovative building, developed on a hospital site that
      has been practising medicine and particularly the treatment of, and research
      into, cancer for over 100 years.

PMID- 15729995
TI  - Reliability-centred approach evaluated.
AB  - Reliability-centred maintenance is the process used to determine the most
      effective maintenance approach. RCM takes a system approach when evaluating the
      consequences of failure. Run-to-fail is sometimes an acceptable maintenance
      approach. Condition monitoring is often the most effective maintenance approach.

PMID- 15729996
TI  - Management map for tomorrow.
AB  - The way forward for hospital services and facilities management is examined by
      Francisco Castella, Doctor of Engineering and a member of the International
      Federation of Hospital Engineering Council. In this article, which is based on a
      paper presented at the 18th IFHE Congress, he draws on his experience as facility
      manager and director of general services in the Teaching Hospital of Badalona,
      Spain, and on knowledge gained through attending IFHE Congresses - representing
      the Spanish Hospital Engineering Association.

PMID- 15729997
TI  - Engineering expertise sought.
AB  - RedR-IHE (the merged RedR and International Health Exchange) is responding to
      requests from humanitarian agencies for skilled aid and development professionals
      to be deployed to South Asia following the earthquake and tsunami disaster. As
      assistance programmes gain momentum, and reconstruction activities commence, the
      expertise of healthcare sector engineers is likely to be in considerable demand.

PMID- 15729998
TI  - Implementing best construction practice.
AB  - In this article, based on a speech given at last November's Healthcare Estates
      Conference, Minister for Construction Nigel Griffiths sets out the challenges
      facing healthcare estates in the context of NHS reform and modernisation in the
      21st Century.

PMID- 15729999
TI  - Trust management of information vital.
AB  - The Freedom of Information (FOI) Act, which came into force on 1 January this
      year, requires all NHS bodies to disclose, when requested, any information they
      hold. Jason Rayfield reports on the work done by legal firm Morgan Cole to
      prepare NHS Trusts to deal with their responsibilities under the new legislation.

PMID- 15730000
TI  - Ongoing training importance stressed.
AB  - Paul Jenkins, senior training consultant, Eastwood Park, reflects on the forces
      which are creating an unprecedented demand for highly specialised ongoing
      training in the area of decontaminating reusable surgical instruments.

PMID- 15730002
TI  - Real-time simulation value proved.
AB  - A clear visual display medium allowing the viewer to comprehensively "explore" a
      proposed environment has tremendous merit, Arup stresses.

PMID- 15730001
TI  - Medical device uptake challenged.
AB  - Hailed as the most important initiative to date between Government and the
      medical devices industry, the recently published Healthcare Industries Task Force
      report sets out a programme of action aimed at benefiting patients through the
      introduction of leading-edge medical technology. Jason Rayfield reports.

PMID- 15730003
TI  - Drainage systems must not pose risk.

PMID- 15730004
TI  - [Interferons alpha in the treatment of chronic HCV infections].
AB  - Interferons play the main role in the treatment of chronic hepatitis C. In the
      clinical practice recombined forms of these cytokines dominate. Most recent
      obligatory standard of the treatment is combined therapy with pegylated
      interferon and ribavirin during 24 or 48 weeks dependent of HCV genotype. In some
      clinical cases, in which contraindications to these forms of drugs or adverse
      events appear, administration of natural interferon (alphaferon) is possible.
      Treatment with this form of interferon in these cases is safe and efficient.

PMID- 15730005
TI  - [Molecular epidemiology of chronic hepatitis C (HCV) virus].
AB  - Hepatitis C virus (HCV) is a major etiologic causative agent of chronic
      hepatitis, cirrhosis with its attendant risks of hepatocellular carcinoma.
      Efforts to isolate the virus by standard immunologic and virologic techniques
      were unsuccessful and HCV was finally identified by direct cloning and sequencing
      of its genome. Although the virus was identified 15 years ago, its pathogenesis
      and replication are not fully understood. Progress in the molecular biology of
      HCV was achieved by expressing viral recombinant proteins in culture cells and
      utilizing recombination DNA techniques. An important feature of HCV is that the
      viral genomes display extensive genetic heterogeneity at the local as well as the
      global level. Within a host, the HCV genome population circulates as a 'quasi
      species' of closely related sequences. Worldwide, a high degree of genetic
      variation exists resulting in at least six major genotypes of more distantly
      related subtypes. It has been reported, that the prevalence of each subtype
      varies in different geographical areas and that virus pathogenicity and
      sensitivity to interferon treatment, appear to vary with different subtypes.

PMID- 15730006
TI  - [Chronic hepatitis C infection--mechanisms of virus "immune escape"].
AB  - The characteristic feature of HCV infection is the presence of both humoral and
      cellular immune response. In spite of the immune activation the host is unable to
      eradicate the virus. Spontaneous resolution of chronic infection is exceedingly
      rare--it is estimated at 0.6% per year. The currently available combination
      therapies with alpha interferon and ribavirin are effective in limited groups of
      patients. Factors involved in the mechanism(s) whereby HCV establishes and
      maintains its persistence are not well understood. The high genetic variability
      of HCV allows the virus to passively evade the immune system. Data obtained from
      experiments with cell culture expressing HCV proteins suggest that viral
      persistency is a multifactorial mechanism. Several viral genes impair cellular
      functions involved in immune responses.

PMID- 15730007
TI  - [Incidence of hepatitis C in the Silesian voivodeship in the years 1997-2002].
AB  - The aim of the study was to examine the incidence of viral hepatitis type C (HCV)
      in the general population of Silesian voivodeship (Poland), in the years 1997
      2002. Since 1997 HCV is a notifiable disease in Poland, reported by diagnosing
      physicians to local sanitary-epidemiological centers. Analysis included the total
      of 875 records collected in 1997-2002 by all sanitary-epidemiological centers in
      the Voivodeship. In that period the voivodeship annual incidence varied between
      2.2/100000 and 2.9/100000. Most of the incidence cases were urban dwellers
      (82.5%), compared to rural dwellers (17.5%), and the age-structure was dominated
      by people above 65 years (13.%) as well as young persons aged 20-24 years (9.8%).
      The results revealed a large county-to-county variation in incidence. This
      finding could be hardly explained on the ground of available data--there are no
      major between-county differences in terms of health care quality, provision and
      availability of health care services, demographic or socio-economic factors in
      Silesian voivodeship. The likely explanation points to unequal or even
      questionable functioning of the HCV reporting scheme that--on a voivodeship level
      -could result in an underestimation of incidence of the disease. This hampers a
      possibility of specific analyses based on the existing, secondary data and
      justifies a need for improvement of the register. The necessary action should
      involve subject-oriented training of all participants of the reporting system, as
      well as health professionals engaged in diagnosing and treatment of infectious
      diseases.

PMID- 15730008
TI  - [Clinical course of Lyme borreliosis with respect to the initial disease
      manifestation in Bialowieza residents].
AB  - The aim of the study was to evaluate relationship between initial manifestation
      of Lyme borreliosis and further course of the disease. Files and questionnaires
      regarding present and past course of the disease were evaluated in 138 residents
      of Bialowieza village, suffering previously from Lyme borreliosis. Present
      arthralgia was the most frequently reported by persons who initially were
      diagnosed as suffering from Lyme arthritis. Ischialgia and brachialgia were the
      most prevalent in patients with previous neuroboreliosis. Psychiatric evaluation
      demonstrated significantly more frequent prevalence of sleep and cognitive
      disturbances in persons with previously diagnosed neuroboreliosis. Persons with
      initial joint manifestations of Lyme borreliosis more frequently report
      arthralgia in further follow-up. Primary manifestation of the disease as
      neuroboreliosis increase risk of subsequent disturbances of sleep and cognition.

PMID- 15730010
TI  - [Risk of alveococcosis for humans in Poland].
AB  - The paper presents data on occurrence, diagnosis and treatment of alveolar
      echinococcosis in humans as well as possible methods of its prevention. Studies
      done in 2001-2003 in Poland have shown the high prevalence of the tapeworm in red
      foxes in the north-east (34.5%) and south-east (39.3%) of Poland with foci of
      infection in some counties (up to 70% foxes infected). It makes the high
      potential risk for human infection in these areas.

PMID- 15730009
TI  - [Activity of lysosomal exoglycosidases in serum of patients with chronic borrelia
      arthritis].
AB  - To estimate activities of lisosomal exoglycosidases in serum of patients with
      chronic borrelia arthritis. Study group consisted of 18 patients aged 18-72 years
      (x=46) hospitalized in Department of Infectious Diseases and Neuroinfections of
      Medical Academy in Bialystok with diagnosis of chronic arthritis in course of
      borreliosis. Control consisted of 20 healthy volunteers (health services
      employees) aged 25-65 years (x=45), with no detectable anti-Borrelia burgdorferi
      antibodies in serum. In all borreliosis patients serum activity of: N-acetyl-beta
      D-glucosaminidase (HEX), beta-galactosidase and alpha-mannosidase was measured
      before and after 4 weeks of doxycycline treatment. Results were analyzed with
      Statistica 6.0 software. P < 0.05 was considered statistically significant. HEX
      activity was significantly increased in serum of Lyme arthritis patients before
      treatment compared to controls. It decreased after 4-week treatment, remaining
      insignificantly higher than in controls. b-galactosidase and a-mannosidase
      activities in serum of Lyme arthritis patients were insignificantly higher than
      in controls and fell after treatment to the levels observed in control group. N
      acetyl-beta-D-glucosaminidase (HEX) is sensitive enzymatic marker of Lyme
      arthritis. It may be used to monitor course of the disease and its efficiency of
      treatment.

PMID- 15730011
TI  - [Nosocomial rotavirus infections].
AB  - Rotaviral infections in children are the important problem occurring worldwide.
      Little children under 5 years of age with rotaviral diarrhea usually need stay in
      the hospital because of severe course: fever over 38 C, vomiting, diarrhea
      leading to dehydration and disturbances in electrolyte and acido-alkalic balance.
      These children are the source of the nosocomial rotaviral infection in the other
      children hospitalizing because of the other cause then diarrhea. Rotaviral
      nosocomial infections have 23.8%-43% of participation in the world and 4.5%-45.4%
      in Poland in all hospitalizing rotaviral infections. Transmission of infection
      inside the hospital ward happens by not-washing hands of the staff, mothers
      remaining with their children, disregarding hospital regime. Lack of the
      isolation of patients with diarrhea and prolonged stay in the hospital are also
      agents predestinating to nosocomial rotaviral infections. Elimination of these
      agents, implementation of supplementary diet with antibodies or Lactobacillus GG
      may limit account of nosocomial rotaviral infections but will not stop them. The
      only way of prevention of the rotaviral infections and nosocomial rotaviral
      infections is implementation of effective and save rotaviral vaccine, which will
      be suitable for infants and toddlers worldwide.

PMID- 15730012
TI  - [Prospective study of rotaviral infections in children hospitalized at the Clinic
      of Pediatric Infectious Diseases in Bialystok in 2003].
AB  - Rotavirus is the most common gastrointestinal pathogen in infants and young
      children. The aim of this study was to determine the role of rotavirus in acute
      diarrhea in children hospitalized in Pediatric Infectious Diseases Clinic in
      Bialystok. 658 children aged 0-7 years admitted to the ward: 466 children with
      gastroenteritis and another 192 without any diarrheic symptoms were tested for
      rotavirus infection by latex agglutination. Rotavirus was detected in 16.1% stool
      specimens collected from children with acute diarrhea. None of patients without
      diarrhea was positive for rotavirus on admission--2% of this patients acquired
      symptomatic rotavirus infection during hospitalization. This study delivers
      epidemiological data on rotavirus infection and shows the need of further study
      on etiology of viral gastroenteritis in children in our district.

PMID- 15730013
TI  - [Implementation of the Active Nosocomial Infections Surveillance System in Polish
      hospitals].
AB  - Characteristics the organisation of infection control in hospitals participating
      in the Active Nosocomial Infections Surveillance System in Poland. Analysis of
      the data obtained from a questionnaire on organization of nosocomial infections
      surveillance in hospitals participating in the Active Nosocomial Infections
      Surveillance System coordinated by the Polish Society of Hospital Infections.
      Analyzed data were obtained from 32 hospitals of different size number of
      hospital beds) and type of reference. Most questions focused on the structures of
      infection control, postdischarge surveillance and role of microbiological
      laboratory. NIs surveillance system is based on the work of infection control
      team consisting of epidemiological nurse and physician representing different
      specializations, but there is no specialist or doctor specializing in medical
      microbiology. Additionally, the Infection Control Committee exists in 25
      hospitals. Only in 37.5% of those hospitals the postdischarge surveillance is
      performed, but related only to surgical site infections. There is no
      microbiological surveillance in 25% of the hospitals, which means that neither
      registration nor collecting of drug-resistant strains are performed.
      Implementation of the Active Nis Surveillance System is based on the common
      organizational structure, programme and definitions of infections. The
      postdischarge surveillance and microbiological surveillance are the main
      activities which still need improvement.

PMID- 15730014
TI  - [Incidence of tuberculosis in the population of Kalisz in the years 1991-2000].
AB  - The aim of the paper was to study the incidence of tuberculosis in the population
      of Kalisz in the years 1991-2000. This incidence was analysed in respect to age
      and sex. Tuberculosis epidemiological status in Kalisz was compared to that
      observed nationwide. The material were the cases of tuberculosis reported in
      Kalisz in the years 1991-2000. Descriptive methods of epidemiology were applied
      for the assessment of data. 378 cases of tuberculosis were registered in Kalisz
      in the years 1991-2000. Incidence rates in individual years varied from 43.1 in
      1996 to 27.8 in 2000. After 1996 a marked fall in the incidence was noted. New
      cases (78.6% of all) were found in 92 females and 205 males, and relapses (21.4%
      of all cases) in 21 females and 60 males. The majority of cases were reported in
      20-44 year old group (42.3%), and the highest incidence rate was observed in the
      group of 65 year old patients and older (107.6). The incidence in males was 1.6
      to 4.5 times greater than in females.

PMID- 15730015
TI  - [Assessment of the sterilization of medical devices--an important challenge to
      health care in Poland].
AB  - The aim of the study was the evaluation of sterilization of medical devices in
      Polish hospitals. The system that we use to establish which sterilization
      procedures should be employed to reduce the risk of hospital infections
      associated with medical devices. Based on inquiries, the conditions for the
      sterilization of medical devices in 21 Warsaw hospitals were assessed. The
      following issues were taken into consideration: preparation of medical supplies
      for sterilization, methods of sterilization and the monitoring system. In order
      to evaluate hygienic conditions due to sterilization points system was applied.
      10% of the hospitals had Central Sterilization Service Department with 3 zones
      where automatic washing and disinfection, sorting, packaging, sterilization and
      storage of medical devices had been performed. The other 20% had CSSD without
      zones. In more than 65% there were common services for sterilization only.
      Instruments were delivered already prepared for sterilization. In remaining
      hospitals all steps, including sterilization were performed in words. According
      preparation of medical devices for sterilization it was established that mainly
      chemical disinfection just after use and than manual cleaning was used; the
      automatic cleaning in washer-disinfectors is used mainly in CSSD. Steam was the
      preferred method of sterilization, but also low temperature methods were used for
      heat sensitive devices. The monitoring of sterilization processes was
      satisfactory. There were first trials of the validation of the sterilization
      processes. There is still a need for improvement in the sterilization of medical
      devices, especially including: the organisation of CSSD in all Polish hospitals;
      replacement of manual cleaning processes by automatic cleaning; organisation of
      advanced training courses for the heads and staff of the CSSD.

PMID- 15730016
TI  - [Prediction of 29-years mortality rate from initial and emerging risk factors
      during follow-up in a Warsaw population].
AB  - Searching for clues through cohort studies requires introducing initial values of
      predictors likely to forecast future morbid events. This may put the end points
      on unequal footing, due to different timing of preceding exposures. A long follow
      up mortality study of an urban population with repeated measurements in the midst
      of the observation enabled splitting predictors of death into time-related
      components making comparisons more alike with regards to time. A random sample of
      1898 Warsaw adult population was interviewed in 1970 on a variety of demographic,
      social, behavioural and morbid circumstances as well as the use of health
      services. The 29-year-long search for death events was instituted with 751
      (39.5%) deaths ascertained till the end of 1999 and 166 persons not traced
      (8.7%). In 1979 the inquiry was repeated in 1366 respondents alive and ready to
      take part, with the same set of questions asked. Beyond base-line values of
      traits in question, the estimates of change (possible predictors both times;
      appearance or vanishing of a trait; no trait whatsoever; no answer) were arranged
      as dummy variables tested for creating an excess risk against double absence of
      exposure. Cox multiple regression models were used for assessing relative odds of
      death. The base-line '70 predictions limited the risk of death for women mainly
      to non-structured evidence of disease whereas among men they included social
      circumstances, smoking & bronchitis, and possession of a personal doctor. With
      the '79 base-line recent hospital discharge was added to the prediction of
      remaining ('80-'99) mortality experience of both sexes, and disability appeared
      as a risk factor in men. Using time-related variables disclosed the mortality
      boosting influence of twice-confirmed smoking in both sexes, as well as the
      excess death following the so far absent protracted illness among men and women.
      The appearance of the excess risk of death due to addition of hitherto neutral
      exposures was more frequent among men than women. The same pattern of the new
      exposures emerged for recent hospital discharge vs. no hospitalization. It seems
      that arranging exposure in the time-related fashion discloses a newly evolving
      excess risk of death which may pave the way towards death in more vulnerable
      fraction of a population in largely non-specific fashion.

PMID- 15730018
TI  - [Use of prenatal health care and risk of infants born small-for-gestational-age.
      Preliminary results of a case-control study in the Lodz voivodeship].
AB  - It is well documented that small-for-gestational age (SGA) infants are at an
      increased risk of perinatal mortality and morbidity. In order to identify the
      major modifiable risk factors of SGA birth, a case-control study was launched in
      the area of Lodz voivodeship, Poland. The project was focused on the evaluation
      of the role of perinatal health services and avoidance of exposure to tobacco
      smoke in the prevention of SGA births. The study population consisted of mothers
      of 153 SGA infants (cases) and 93 mothers of control infants. SGA infants were
      identified as infants with body weight below 10th percentile for gestational age,
      using Ballarda scale. The controls were non-SGA infants delivered after 37 week
      of gestation. The infants from both groups were delivered in 26 maternity wards
      in the Lodz voivodeship within the period of June 1-November 1, 2003. One month
      after delivery, each mother of SGA and control infants was visited by an
      interviewer who collected information about her profile of use of perinatal
      health care and on active and passive exposure to tobacco smoke in pregnancy.
      Odds ratios and 95% confidence units (CU) were calculated using EpiInfo software
      developed by CDC, Atlanta, Georgia, US. Late booking for perinatal care (after 12
      week of gestation) and less than 5 visits during pregnancy was found to be
      related to an increased risk of SGA, however, the OR values included unity. About
      1/3 of mothers of SGA infants and "of the controls were served mainly by the
      private health sector. The use of private care was related to a lower risk of
      SGA: OR= 0.55 95% CI (0.31-0.96). This protective pattern was observed in the
      population of women aged 19-25 living in rural areas years and with only primary
      education. The preconception visits to obstetricians and contacts with health
      educators during pregnancy were also found to have some protective effect,
      however, the ORs were not statistically significant. The adverse effect of
      smoking during pregnancy was clearly confirmed in the study population, OR= 2.69
      95%CI (1.37-5.33), while the role of passive smoking was difficult to assess due
      to the small number of nonsmoking women exposed to ETS. There are some
      indications that the poor use of perinatal health services may account for the
      elevated risk of SGA births in the Lodz voivodeship. The use of the private
      health sector is growing and seems to be related to a lower risk of SGA births.
      More effective tools to prevent maternal smoking have to be developed and
      implemented in routine perinatal care.

PMID- 15730017
TI  - [Survival of cervical cancer patients in selected regions of Poland in 1990-1996,
      in relation to some prognostic factors].
AB  - To evaluate whether cervical cancer patients in selected regions of Poland show
      similar 5-year survival rates and if they are different from European average
      and, also, to evaluate the effect of selected prognostic factors. The analysis
      based on a cohort of 1386 cervical cancer cases identified by population-based
      Cancer Registries collecting data from Kieleckie and Opolskie voivodships and
      from the City of Warsaw in 1990-96. These data become complete by adding
      information from medical records. The 5-year relative survival rates were
      calculated using the life tables method, and, a multivariant regression analysis
      was applied for evaluation of prognostic factors. The regions differed
      significantly in stage distribution (p<0.001), however, they were similar in age
      groups and histological diagnosis. The age-standardized relative 5-year overall
      survival rate was 52.2%, and was among lowest rates in Europe. The rate in
      Kieleckie was 60.7%; in Opolskie--43.3%, and in Warsaw--51.9%. The rates for
      Stage I in those regions were comparable at over 80%, but were different for
      Stage II and higher stages. The multivariant analysis showed a significant risk
      increase related to stage advancement (p<0.0001) as well as to the place of
      living in Opolskie (p=0.02) and to the adenocarcinoma diagnosis (p=0.05).
      However, the analysis did not confirm the effect of age of diagnosis as a
      prognostic factor. The overall, age-standardised 5-year relative survival rates
      of cervical cancer patients are one of the lowest in Europe, though diversified
      in the regions. They are almost satisfactory and close to European average in
      Kieleckie where prevention was effective, but poor in the other regions. The low
      survivals overall are basically due to the unsatisfactory proportion of the early
      stage of disease. The uneven survivals of patients with Stage II and higher
      stages of cancer in the selected regions of Poland suggest different standards of
      treatment.

PMID- 15730019
TI  - [Frequency, diagnostic criteria and consequences of bacterial vaginosis in
      pregnant women].
AB  - Vaginal discharge based on changes in a vaginal ecosystem (decreasing number of
      Lactobacillus and increasing number of Mobiluncus spp., Gardnerella vaginalis,
      Prevotella spp., Mycoplasma hominis, Peptostreptococcus spp) appears to be a
      major cause of bacterial vaginosis. Bacterial vaginosis is associated with:
      preterm delivery, premature rupture of membranes, chorioamnionitis, amniotic
      fluid infection, endometritis, low-weight neonates. The role of natural
      microflora of vagina, the most important diagnostic criteria, epidemiology and
      immunological changes in pregnant women with bacterial vaginosis are discussed in
      the light of the recent publications.

PMID- 15730020
TI  - [The advertising of medicinal products to the public in Poland--legislative,
      ethical, health and social concerns].
AB  - Regulations regarding the advertising of medicinal products to the public in
      Poland, EC directive and WHO ethical criteria for medicinal drug promotion were
      compared. Current Polish regulations varied considerably with Community's and WHO
      point of view. The article covers the potential health and social effects of the
      recent situation in the area of medicines advertising in Poland.

PMID- 15730021
TI  - Enhanced anaerobic biodegradation of BTEX-ethanol mixtures in aquifer columns
      amended with sulfate, chelated ferric iron or nitrate.
AB  - Flow-through aquifer columns were used to investigate the feasibility of adding
      sulfate, EDTA-Fe(III) or nitrate to enhance the biodegradation of BTEX and
      ethanol mixtures. The rapid biodegradation of ethanol near the inlet depleted the
      influent dissolved oxygen (8 mg l(-1)), stimulated methanogenesis, and decreased
      BTEX biodegradation efficiencies from > 99% in the absence of ethanol to an
      average of 32% for benzene, 49% for toluene, 77% for ethylbenzene, and about 30%
      for xylenes. The addition of sulfate, EDTA-Fe(III) or nitrate suppressed
      methanogenesis and significantly increased BTEX biodegradation efficiencies.
      Nevertheless, occasional clogging was experienced by the column augmented with
      EDTA-Fe(III) due to iron precipitation. Enhanced benzene biodegradation (> 70% in
      all biostimulated columns) is noteworthy because benzene is often recalcitrant
      under anaerobic conditions. Influent dissolved oxygen apparently played a
      critical role because no significant benzene biotransformation was observed after
      oxygen was purged out of the influent media. The addition of anaerobic electron
      acceptors could enhance BTEX biodegradation not only by facilitating their
      anaerobic biodegradation but also by accelerating the mineralization of ethanol
      or other substrates that are labile under anaerobic conditions. This would
      alleviate the biochemical oxygen demand (BOD) and increase the likelihood that
      entraining oxygen would be used for the biotransformation of residual BTEX.

PMID- 15730022
TI  - Potential of preliminary test methods to predict biodegradation performance of
      petroleum hydrocarbons in soil.
AB  - Preliminary tests at different scales such as degradation experiments
      (laboratory) in shaking flasks, soil columns and lysimeters as well as in situ
      respiration tests (field) were performed with soil from two hydrocarbon
      contaminated sites. Tests have been evaluated in terms of their potential to
      provide information on feasibility, degradation rates and residual concentration
      of bioremediation in the vadose zone. Sample size, costs and duration increased
      with experimental scale in the order shaking flasks - soil columns - lysimeter -
      in situ respiration tests, only time demand of respiration tests was relatively
      low. First-order rate constants observed in degradation experiments exhibited
      significant differences between both, different experimental sizes and different
      soils. Rates were in line with type and history of contamination at the sites,
      but somewhat overestimated field rates particularly in small scale experiments.
      All laboratory experiments allowed an estimation of residual concentrations after
      remediation. In situ respiration tests were found to be an appropriate pre
      testing and monitoring tool for bioventing although residual concentrations
      cannot be predicted from in situ respiration tests. Moreover, this method does
      not account for potential limitations that might hamper biodegradation in the
      longer term but only reflects the actual degradation potential when the test is
      performed.

PMID- 15730023
TI  - Monitoring of accelerated naphthalene-biodegradation in a bioaugmented soil
      slurry.
AB  - The effect of microbial inoculation on the mineralization of naphthalene in a
      bioslurry treatment was evaluated in soil slurry microcosms. Inoculation by
      Pseudomonas putida G7 carrying the naphthalene dioxygenase (nahA) gene resulted
      in rapid mineralization of naphthalene, whereas indigenous microorganisms in the
      PAH-contaminated soil required a 28 h adaptation period before significant
      mineralization occurred. The number of nahA-like gene copies increased in both
      the inoculated and non-inoculated soil as mineralization proceeded, indicating
      selection towards naphthalene dioxygenase producing bacteria in the microbial
      community. In addition, 16S rRNA analysis by denaturing gradient gel
      electrophoresis (DGGE) analysis showed that significant selection occurred in the
      microbial community as a result of biodegradation. However, the indigenous soil
      bacteria were not able to compete with the P. putida G7 inoculum adapted to
      naphthalene biodegradation, even though the soil microbial community slightly
      suppressed naphthalene mineralization by P. putida G7.

PMID- 15730024
TI  - Decolorization kinetics of the azo dye reactive red 2 under methanogenic
      conditions: effect of long-term culture acclimation.
AB  - The biological decolorization of the textile azo dye Reactive Red 2 was
      investigated using a mixed, mesophilic methanogenic culture, which was developed
      with mixed liquor obtained from a mesophilic, municipal anaerobic digester and
      enriched by feeding a mixture of dextrin/peptone as well as media containing
      salts, trace metals and vitamins. Batch decolorization assays were conducted with
      the unacclimated methanogenic culture and dye decolorization kinetics were
      determined as a function of initial dye, biomass, and carbon source
      concentrations. Dye decolorization was inhibited at initial dye concentrations
      higher than 100 mg l(-1) and decolorization kinetics were described based on the
      Haldane model. The effect of long-term culture exposure to the reactive dye on
      decolorization kinetics, culture acclimation, as well as possible dye
      mineralization was tested using two reactors fed weekly for two years with an
      initial dye concentration of 300 mg l(-1) and a mixture of dextrin/peptone. The
      maximum dye decolorization rate after a 2-year acclimation at an initial dye
      concentration of 300 mg l(-1) was more than 10-fold higher as compared to that
      obtained with the unacclimated culture. Aniline and the o-aminohydroxynaphthalene
      derivative resulting from the reductive azo bond cleavage of the dye were
      detected, but further transformation(s) leading to dye mineralization were not
      observed. Reactive Red 2 did not serve as the carbon and energy source for the
      mixed culture, and dye decolorization was sustained by the continuous addition of
      dextrin and peptone. Thus, biological decolorization of reactive azo dyes is
      feasible under conditions of low redox potential created and maintained in
      overall methanogenic systems, but supply of a biodegradable carbon source is
      necessary.

PMID- 15730025
TI  - Aerobic cometabolism of chloroform by butane-grown microorganisms: long-term
      monitoring of depletion rates and isolation of a high-performing strain.
AB  - The focus of this microcosm study was to monitor the performances of 17 butane
      utilizing microcosms during a long-term (100-250 days) aerobic cometabolic
      depletion of chloroform (CF). The depletion of the contaminant began after a lag
      time variable between 0 and 23 days. All microcosms quickly reached a pseudo
      steady-state condition, in terms of biomass concentration (with an average of 9.3
      x 106 CFU ml(-1)), chloroform depletion rate (5 micromol l(-1) d(-1)) and butane
      utilization rate (730 micromol l(-1) d(-1)). After about 100 days of CF
      depletion, a sudden 5- to 7-fold increase of the chloroform rate was observed in
      two microcosms, where the highest amount of contaminant had been depleted. In one
      of these high-performing microcosms, an experiment of chloroform depletion in the
      absence of butane resulted in the depletion of a surprisingly high amount of
      contaminant (765 micromolCF kg(-1) dry soil in 2 months) and in a marked
      selection of a single bacterial strain. Bioaugmentation assays conducted with the
      biomass selected in this microcosm and with a pure culture of the selected strain
      immediately resulted in very high chloroform depletion rates. Preliminary results
      of a study conducted with resting cells of the selected strain indicated that it
      can degrade chloroform concentrations up to 119 microM (14.2 mg l(-1)) without
      any sign of substrate toxicity, and that it is able to transform vinyl chloride
      and 1,1,2-trichloroethane.

PMID- 15730026
TI  - Enhanced biodegradation of transformer oil in soils with cyclodextrin--from the
      laboratory to the field.
AB  - The use cyclodextrins for the intensification of bioremediation by improving the
      mobility and bioavailability of contaminants has recently been studied. In this
      work, the role of randomly methylated beta-cyclodextrin in the bioremediation of
      soils contaminated with transformer oil was studied both in bench scale
      bioreactors and through field experiments. The aims of this research were to (a)
      establish the scientific background of a cyclodextrin-based soil bioremediation
      technology, (b) demonstrate its feasibility and effectiveness in the field, and
      (c) develop an integrated methodology, consisting of a combination of physical,
      chemical, biological and ecotoxicological analytical methods, for efficiently
      monitoring the technology performances. The stepwise increasing scale of the
      experiments and the application of the integrated analytical methodology
      supported the development of a scientifically established new technology and the
      identification of the advantages and the limitations of its application in the
      field. At each phase of the study, randomly methylated beta-cyclodextrin was
      found to significantly enhance the bioremediation and detoxification of the
      transformer oil-contaminated soils employed by increasing the bioavailability of
      the pollutants and the activity of indigenous microorganisms.

PMID- 15730027
TI  - Bacterial community dynamics during in-situ bioremediation of petroleum waste
      sludge in landfarming sites.
AB  - In-situ bioremediation of petroleum waste sludge in landfarming sites of Motor
      Oil Hellas (petroleum refinery) was studied by monitoring the changes of the
      petroleum composition of the waste sludge, as well as the changes in the
      structure of the microbial community, for a time period of 14 months. The
      analyses indicated an enhanced degradation of the petroleum hydrocarbons in the
      landfarming areas. A depletion of n-alkanes of approximately 75-100% was
      obtained. Marked changes of the microbial communities of the landfarms occurred
      concomitantly with the degradation of the petroleum hydrocarbons. The results
      obtained from terminal restriction fragment length polymorphism (T-RFLP) analysis
      of polymerase chain reaction (PCR) amplified 16S rRNA genes demonstrated that
      bacteria originating from the refinery waste sludge and newly selected bacteria
      dominated the soil bacterial community during the period of the highest
      degradation activity. However, the diversity of the microbial community was
      decreased with increased degradation of the petroleum hydrocarbons contained in
      the landfarms. T-RFLP fingerprints of bacteria of the genera Enterobacter and
      Ochrobactrum were detected in the landfarmed soil over the entire treatment
      period of 14 months. In contrast, the genus Alcaligenes appeared in significant
      numbers only within the 10 month old landfarmed soil. Genes encoding catechol 2,3
      dioxygenase (subfamily I.2.A) were detected only in DNA of the untreated refinery
      waste sludge. However, none of the genes known to encode the enzymes alkane
      hydroxylase AlkB, catechol 2,3-dioxygenase (subfamily I.2.A) and naphthalene
      dioxygenase nahAc could be detected in DNA of the landfarmed soils.

PMID- 15730028
TI  - Detection and characterisation of catechol 2,3-dioxygenase in an indigenous soil
      pseudomonad by MALDI-TOF MS using a column separation.
AB  - The key enzyme catalyzing the second step in the phenol degradation meta-cleavage
      pathway (C230) has been purified to homogeneity from a new bacterial strain,
      which belongs to genus Pseudomonas. The species was growing on phenol as carbon
      source. The C230 was detected and identified by absorption spectroscopy. The
      protein was isolated using sucrose density centrifugation and anion exchange
      chromatography. The purified protein showed a molecular mass of 32 kDa to sodium
      dodecyl sulfate polyacrylamid gel electrophoresis and an isoelectric point of 5
      estimated by analytical isoelectrical focusing. Matrix-assisted laser desorption
      ionization-time of flight mass spectrometry and peptide mapping was attempted for
      the identification of the isolated protein and proteins involved in the metabolic
      pathway.

PMID- 15730029
TI  - Evaluation of heavy metal availability prior to an in situ soil phytoremediation
      program.
AB  - Metal mobility and the fractionation of elements and thus the biological uptake
      of Zn, Pb and Cd by plants were investigated using a simplified analytical
      procedure for soluble and bioavailable metals using a four-step sequential
      extraction procedure. Results showed that there was a low proportion of
      immediately soluble metals, as well as a high proportion of metals that could be
      released and would so be available for plant uptake. In the sequential extraction
      procedure, considering the total partition, there was a large proportion of Pb,
      Cd and Zn extracted in a readily mobile form. In acidic soils the content of
      metals in ready mobile form (exchangeable-bound to carbonates as well as to Fe
      and Mn oxides) and bound to organic matter constitutes an important source of
      potentially available elements. The same pattern was observed in alkaline soils,
      where almost 80% of the metals could be remobilized and be potentially available
      to plants. Knowing the metal partitioning and mobility of heavy metals it is very
      important for evaluating the phytoremediation efficiency.

PMID- 15730030
TI  - [Lithium, a potentially dangerous drug].
AB  - Two patients with a bipolar disorder, a woman aged 56 and a woman aged 68, who
      had used lithium for more than 30 years, were seen with side effects from this
      medication. Both patients were treated by their general practitioner and had not
      visited a psychiatrist for many years. The first patient had a chronic lithium
      intoxication with cerebellar signs and eventually coma, diabetes insipidus,
      hyperthyroidism, hyperparathyroidism and psoriasis. After 6 weeks of treatment in
      the intensive-care unit she made a good recovery. The second patient had several
      lithium side effects. She was diagnosed with diabetes insipidus,
      hyperparathyroidism due to a parathyroid adenoma, hypothyroidism and a sick-sinus
      syndrome. A pacemaker was implanted 4 years earlier. The adenoma was surgically
      removed. After other medication was tried, the patient was once again given
      lithium, on which she was able to function well. The first patient had lithium
      concentrations above the therapeutic value for several years and both patients
      experienced a delay before their signs and symptoms were attributed to lithium.
      Lithium treatment should be monitored by an experienced psychiatrist.

PMID- 15730031
TI  - [Organ Donation Act: against an objection system].
AB  - The Organ Donation Act (1998) has not resulted in an increase in donated organs.
      However, it should not be changed from a system registering consent to post
      mortem donation to one in which objection is registered. The consent system is
      more suitable to ensuring the freedom to donate or not, and a system registering
      objection may not increase the number of donated organs. More serious
      implementation of the current system could however achieve this.

PMID- 15730032
TI  - [The practice guideline 'Miscarriage' (second revision) from the Dutch College of
      General Practitioners; a response from the perspective of general practice].
AB  - The practice guideline 'Miscarriage' has been reviewed for the second time in
      fifteen years. It provides the practitioner with distinct diagnostic tools for
      vaginal bleeding in the first sixteen weeks of pregnancy and a clear management
      algorithm. The management of miscarriage is based on a joint decision between the
      general practitioner and the woman concerned. A more reserved attitude towards
      the surgical termination of pregnancy is advised. The guideline sufficiently
      addresses the issue of informing the woman as to the expected amount of bleeding
      during a miscarriage and the relationship with fertility. However, the risk
      factors for heavy blood loss are not mentioned in the guideline. The
      psychological impact of early miscarriage on women is given adequate attention
      and is part of the counselling during the follow-up period. Finally, the medical
      treatment of threatened miscarriage seems to result in an earlier miscarriage
      with less loss of blood compared to expectant management. The guideline pays also
      attention to medical treatment. Future research will clarify whether medical
      treatment is feasible in general practice.

PMID- 15730033
TI  - [The practice guideline 'Miscarriage' (second revision) from the Dutch College of
      General Practitioners; a response from the perspective of gynaecology].
AB  - In March 2004, the Dutch College of General Practitioners issued its revised
      guideline on the management of miscarriage. The older version of the guideline
      advised expectant management of all patients with first-trimester vaginal
      bleeding without ultrasonographic evaluation. In contrast, the new version has
      accepted the importance of ultrasonographic assessment, which offers insight into
      the patient's prognosis. This enables GPs to discuss the further management
      options with women in whom a non-vital pregnancy has been diagnosed: expectant
      management or referral to a unit for removal of the products of conception by
      means of vacuum curettage. Since the patient's management preferences have now
      also been acknowledged, the new guideline is better for all parties involved in
      this common clinical problem.

PMID- 15730034
TI  - [Indications for bone marrow biopsy in adults].
AB  - Bone marrow biopsies are more and more often part of the work-up of patients with
      haematological disorders. The most important reason for this is the fact that a
      biopsy supplies important additional information compared to an aspirate alone.
      Biopsies are superior for the assessment of the bone marrow architecture, the
      vascularisation, the cellularity, the localisation and the extent of infiltrates
      and the degree of fibrosis. In addition, biopsy is a good way to evaluate the
      effects of therapy in the course of the disease. As is the case with aspirates,
      examination of a biopsy alone is usually sufficient for a correct diagnosis.
      However, a combination of both techniques makes possible an optimal assessment of
      the nature and extent of the disease process in the often very serious
      haematological conditions that we are dealing with here.

PMID- 15730035
TI  - [Nonalcoholic steatohepatitis: diagnosis, pathogenesis, treatment and prognosis].
AB  - Nonalcoholic steatohepatitis and chronic viral hepatitis C are the two dominant
      liver diseases in the Netherlands. Hepatic steatosis is usually innocuous but in
      twenty percent of patients it develops into steatohepatitis. One-fifth of these
      patients develop liver cirrhosis and hepatocellular carcinoma can also be a
      consequence of the disease. Nonalcoholic steatohepatitis is characterized by
      macrovesicular steatosis, necroinflammation, loss ofhepatocytes and fibrosis.
      Nonalcoholic steatohepatitis often is associated with type 2 diabetes mellitus,
      hypertension, dyslipoproteinemia and obesity. Insulin resistance plays a major
      role in the pathogenesis of this disease. Drugs against insulin resistance can
      ameliorate nonalcoholic steatohepatitis. Gradual weight loss, a diet including
      polyunsaturated fatty acids and exercise are other important treatment components
      of this condition.

PMID- 15730036
TI  - [Summary of the practice guideline 'Miscarriage' (second revision) from the Dutch
      College of General Practitioners (NHG)].
AB  - The NHG practice guideline 'Miscarriage' provides guidelines for the diagnosis
      and management of pregnant women with vaginal bleeding during the period up to
      and including the 16th week after the first day of the last menstruation. The
      guideline has been revised on the basis of the developments over the last few
      years. The most important modifications are: In case of an imminent miscarriage,
      more consideration than before is given to the patient's preference with regard
      to ultrasonography, expectant management and curettage. The GP should therefore
      discuss the advantages and disadvantages of these options with the patient. A
      midwife was involved in the formulation of the new guideline. Referral from a GP
      to a midwife for transvaginal ultrasonography is offered as one of the
      possibilities. The paragraph on 'information' has been expanded on the basis of
      the results of a patient focus group.

PMID- 15730037
TI  - [Diagnostic image (226). A man with a painful upper arm].
AB  - A 55-year-old man suffered a distal avulsion of the brachial biceps tendon.

PMID- 15730038
TI  - [From gene to disease; from CLN1, CLN2 and CLN3 to neuronal ceroid
      lipofuscinosis].
AB  - The neuronal ceroid lipofuscinoses (NCL) are worldwide the most common lysosomal
      storage disorders of childhood. Clinical features often include progressive
      visual impairment, seizures, psychomotor deterioration, dementia, and premature
      death. Most NCL cases are caused by mutations in the CLN1, CLN2 and CLN3 genes,
      which play an essential role in lysosomal protein degradation. Laboratory
      diagnostics for a patient suspected of NCL should start with enzyme analysis in
      the case of INCL and LINCL and investigation of lymphocyte vacuolisation for
      JNCL. Diagnosis at the protein level is not available for JNCL, but CLN3 mutation
      analysis is possible. The carrier status of healthy relatives in families with
      known mutations in either CLN1, CLN2, CLN3 or CLN6 can be determined with
      certainty by mutation analysis.

PMID- 15730039
TI  - [More and faster notification of infectious disease if notification is carried
      out by the laboratories instead of the diagnosing physician].
AB  - OBJECTIVE: To investigate if notification by the laboratories of a number of
      Group B diseases (meningococcal disease, whooping cough and hepatitis A) which
      according to the Communicable Disease Law of 999 must be reported to the local
      public health authority, would increase the number of reports and the speed at
      which the reports were made. DESIGN: Comparative study. METHOD: In the
      participating regions (Den Bosch and north-east Brabant) it was decided that the
      laboratories would notify the authorities of cases ofmeningococcal disease,
      whooping cough and hepatitis A. The notifications were compared with those from
      the middle-Brabant region which was used as a control. This took place in
      1997/'98, prior to the start of the notification project and in 2000/'02 when it
      was running. The number of positive cases of infectious disease confirmed by the
      laboratories that were reported to the local health authorities and to the
      Inspectorate of Public Health Services was examined - this is known as the degree
      of notification. The number of days from diagnosis to notification of the local
      health authorities was also examined - this is known as the speed of
      notification. RESULTS: The degree of notification for these three diseases
      improved from 6I-89% to 87-95% if the authorities were notified by the
      laboratories. In the control region the degree of notification improved from 29
      4I% to 54-60%. The speed of notification increased significantly if notification
      was done by the laboratories. CONCLUSION: Based on these results it is
      recommended that the Communicable Disease Law be adapted to allow the
      laboratories to notify the authorities of cases of infectious disease.

PMID- 15730040
TI  - [A Dutchman from Mali with a perianal ulcer caused by cutaneous amoebiasis].
AB  - A 66-year-old Dutchman, living in Mali, presented with an extensive progressive
      perianal ulcer despite local and antibiotic treatment. Microscopic examination of
      the stool revealed Entamoeba histolytica/dispar cysts and phagocytosing
      trophozoites were seen in fresh scrapings of the ulcer, a diagnostic feature of
      infection with E. histolytica. The diagnosis was cutaneous amoebiasis and the
      patient was effectively treated with metronidazole and local debridements.
      Primary cutaneous amoebiasis is a rare disease. Diagnosis and treatment are
      relatively simple but lack of familiarity with the disease may lead to
      misdiagnosis or diagnosis at a late stage ofthe infection.

PMID- 15730041
TI  - [A swelling in the knee cavity, not caused by a Baker's cyst but by a nerve
      sheath tumour].
AB  - In a woman, aged 30 years, who presented with a right popliteal mass, a Baker's
      cyst (popliteal cyst) was diagnosed. Five years later she developed symptoms that
      were attributed to compression of the peroneal nerve by the mass. Because of the
      troublesome nature of these symptoms, it was decided to excise the mass.
      Immediately after the operation, a complete loss offunction ofthe common peroneal
      nerve was apparent. Histopathologic examination revealed an ancient schwannoma
      (nerve sheath tumour). The most important reason for not having diagnosed the
      schwannoma was that it was not considered in the differential diagnosis of the
      popliteal mass. Although Baker's cysts are the most common popliteal masses,
      nerve sheath tumours should also be considered in the differential diagnosis.

PMID- 15730042
TI  - [Trial therapy with proton pump inhibitors is not a suitable test for
      gastroesophageal reflux disease; a meta-analysis of the diagnostic test
      characteristics].

PMID- 15730043
TI  - [The increase in pneumonia-related morbidity and mortality among adults in the
      Netherlands and possible explanations for it].

PMID- 15730044
TI  - [Radiography of the medial ends of the clavicles by the method of the Dutch
      Immigration and Naturalisation Service is unsuitable for determining adulthood].

PMID- 15730045
TI  - [Pregnant, addicted prostitutes: compulsory admission is sometimes necessary in
      the interests of the child].

PMID- 15730046
TI  - Association of C-509T and T869C polymorphisms of transforming growth factor-beta1
      gene with susceptibility to and progression of IgA nephropathy.
AB  - AIMS: Transforming growth factor (TGF)-beta1 is a cytokine with both beneficial
      anti-inflammatory effects and detrimental profibrotic activity in the
      pathophysiology and progression of glomerulonephritides. The transcriptional
      activity of the gene for TGF-beta1 and the plasma levels of TGF-beta1 protein are
      associated with C-509T polymorphism at the promoter region, and with T869C (Leu
      10Pro) polymorphism at codon 10, of the TGF-beta1 gene. METHODS: Using PCR-RFLP
      and the amplification refractory mutation system PCR, we investigated the C-509T
      and T869C polymorphisms, respectively, to elucidate whether allele frequency
      differences exist between IgA nephropathy (IgAN) patients who were followed up
      for at least 3 years (n = 108) and a normal population (n = 55). We also
      determined the correlations between the TGF-beta1 polymorphisms and the
      progression of IgAN. RESULTS: In C-509T polymorphism, there were significant
      differences in genotype frequency between IgAN patients and normal controls (CC:
      CT: TT, 20:29:33 vs. 11:31:13, chi2 = 6.299, p = 0.043). In Kaplan-Meier survival
      analysis, the patients with TT genotype showed a poorer renal survival than those
      with CC + CT genotypes (p = 0.042). In T869C polymorphism, there were also
      significant differences in genotype frequency between IgAN patients and normal
      controls (TT : TC : CC, 4 : 79 : 25 vs. 0 : 52 : 2, chi2 = 12.552, p = 0.002).
      The initial serum creatinine (Scr) level was higher in the patients with CC
      genotype than in those with TT + TC genotypes. In Kaplan-Meier survival analysis,
      the patients with CC genotype showed a poorer renal survival than those with TT +
      TC genotypes, but not to a statistically significant extent (p = 0.076). In the
      combined survival analyses, the high TGF-beta1 producer group showed a poor renal
      survival rate (p = 0.014). CONCLUSION: Compared to normal population, the
      frequencies of genotypes producing high TGF-beta1 protein were higher in IgAN
      patients. Moreover, patients with genotypes producing high TGF-beta1 plasma
      levels showed a poor renal survival rate.

PMID- 15730047
TI  - Initial functional status predicts infections during steroid therapy for renal
      diseases.
AB  - BACKGROUND AND AIM: Corticosteroid therapy is an effective way of treatment for
      many renal diseases, however, it is sometimes associated with infections. Our aim
      is to identify useful predictive markers of infection during steroid therapy.
      METHODS: We examined 121 patients (M/F = 71/50, mean age 43.8, range 15 - 82
      years) who were treated with corticosteroids (IgA nephropathy in 51, minimal
      change disease in 17, membranous nephropathy in 16 rapidly progressive
      glomerulonephritis (RPGN) in 13, lupus nephritis in 12 and other disorders in
      12). Karnofsky's performance score (KPS) was employed to assess the physical
      functional status at the time of diagnosis. Infections were defined as conditions
      that required more than 1-week care, and those that caused the patient's death.
      RESULTS: Nineteen patients (15.7%) had infections during treatment. A logistic
      multivariate analysis showed significant correlations between infection and the
      use of immunosuppressive agents (relative risk RR = 7.7, p = 0.0265), ages of
      52.9 years or more (RR = 13.5, p = 0.0026), initial number of lymphocytes (Lym)
      less than 1.250/microl (RR = 14.2, p = 0.0011), and KPS less than 77.4 (RR =
      12.1, p = 0.0020). All correlations with infection were independent of all the
      other variables listed above. CONCLUSION: KPS, along with age, Lym and the use of
      immunosuppressive agents, are useful for the prediction of infectious
      complications during steroid therapy.

PMID- 15730048
TI  - No effect of fluvastatin on the bone mineral density of children with minimal
      change glomerulonephritis and some focal mesangial cell proliferation, other than
      an ameliorating effect on their proteinuria.
AB  - AIM: There are conflicting data regarding the clinical benefit of the effect of
      HMG-CoA reductase inhibitors (statins) in osteoporosis. We have reported that
      fluvastatin (a statin) is effective in improving proteinuria and renal function
      in childhood IgA nephropathy with mild histological findings and moderate
      proteinuria. The aim of the present study was to clarify the effect of
      fluvastatin on the bone mineral density, bone metabolic markers, proteinuria, and
      renal function of children with minimal change glomerulonephritis with some focal
      mesangial cell proliferation whose glomeruli did not stain positive for IgA and
      on moderate proteinuria. PATIENTS AND METHODS: We conducted a prospective
      controlled study of 36 children who had recently been diagnosed with
      normocholesterolemic minimal change glomerulonephritis with some focal mesangial
      cell proliferation and moderate proteinuria, and in whom strenuous exercise was
      restricted. The 36 patients were randomly assigned to receive 20 mg of
      fluvastatin (group 1) or 5 mg/kg of dipyridamole (group 2) for two years.
      RESULTS: By the end of the trial, there was no difference in BMD between the
      groups, and there were no changes in the four bone metabolic parameters. However,
      the urinary protein, hematuria and BUN levels had significantly decreased in
      group 1 compared to baseline, and the serum total protein and albumin levels and
      creatinine clearance had significantly increased in group 1 compared to baseline
      and group 2. CONCLUSIONS: The results of this study suggest that fluvastatin
      therapy has an antiproteinuric effect and improves renal function in moderately
      proteinuric patients with mild histological glomerulonephritis, but does not
      increase BMD.

PMID- 15730049
TI  - Assessment of glomerular and tubular functions in renal transplant patients
      receiving cyclosporine A in combination with either sirolimus or everolimus.
AB  - AIMS: The aim of this study was to examine the glomerular filtration rate (GFR)
      and tubular function at three months after renal transplantation in two groups of
      patients receiving cyclosporine A associated with either sirolimus (SRL) (n = 18)
      or everolimus (RAD) (n = 12), two structurally similar immunosuppressant drugs.
      RESULTS: Donors' and recipients' characteristics and mean cyclosporine A trough
      levels were similar in the two groups. The mean sirolimus trough level was 12.01
      +/- 1.6 ng/ml whereas the mean everolimus trough level was 4.23 +/- 0.36 ng/ml.
      GFR, equated by the clearance of inulin, was higher in RAD patients (64 +/- 4 ml.
      min- 1.1.73 m(-2)) than in SRL patients (49 +/- 4 ml.min(-1) .1.73 m(-2)) (p <
      0.05). The significant difference in GFR between the groups was not affected by
      differences in mean arterial blood pressures, or by differences in daily
      prednisone dosages, cyclosporine trough levels, or SRL and RAD trough levels.
      Phosphatemia, renal phosphate threshold (TmPO4/ GFR ratio) and uric acid
      clearance were significantly lower in the SRL than in the RAD group, despite
      similar levels of parathyroid hormone. Finally, urinary acid excretion was
      significantly lower in the RAD group. CONCLUSION: In conclusion, regarding
      nephrotoxicity, our preliminary data suggest that it seems to be preferable to
      combine cyclosporine with RAD rather than with sirolimus in renal transplant
      patients. However, long-term renal effects of this combination are still to be
      determined in a larger cohort.

PMID- 15730050
TI  - Recombinant human erythropoietin independence in chronic hemodialysis patients:
      clinical features, iron homeostasis and erythropoiesis.
AB  - AIMS: Recombinant human erythropoietin (r-HuEPO) is widely used to correct renal
      anemia in uremic patients. Interestingly, some chronic hemodialysis (HD) patients
      can maintain high hemoglobin level without the need of r-HuEPO. The aim of this
      study is to investigate clinical features, iron metabolism and erythropoiesis of
      these r-HuEPO-independent HD patients. METHODS: r-HuEPO independence was defined
      in dialysis patients as hemoglobin greater than 12 g/dl and no use of r-HuEPO for
      at least 6 months. An age- and sex-matched group was selected for comparison.
      Their underlying diseases, duration of hemodialysis therapy, efficacy of dialysis
      (Kt/V), normalized protein catabolic rate (nPCR) and body mass index (BMI) were
      recorded. Laboratory data including: hemoglobin, albumin, high sensitivity C
      reactive protein, serum iron, total iron binding capacity, transferrin
      saturation, ferritin, intact parathyroid hormone, soluble transferrin receptor
      (sTfR), serum EPO, cortisol, testosterone, aluminum and leptin levels were
      measured. Renal sonography was also performed in each patient to evaluate renal
      cyst formation. RESULTS: About 2.3% of all HD patients (21/888; M : F = 18 : 3)
      were r-HuEPO-independent. These patients had significantly longer HD duration and
      higher serum EPO and sTfR levels, and lower transferrin saturation rate than
      dependent groups. Correlation analysis revealed that hemoglobin level strongly
      correlated with HD duration, serum sTfR and EPO levels. Levels of sTfR were
      positively related with serum EPO levels and BMI. Multivariate regression
      analysis showed that level of sTfR was the only independent factor related to r
      HuEPO independence. CONCLUSION: R-HuEPO independence is rare among chronic
      hemodialysis patients. Factors contributing to this dependence are complex and
      multiple. Level of serum sTfR parallels erythropoiesis and is the most
      significant factor associated with r-HuEPO independence in chronic HD patients.

PMID- 15730051
TI  - Peripheral vascular disease and serum phosphorus in hemodialysis: a nested case
      control study.
AB  - BACKGROUND: Serum phosphorus (P) and the product of serum calcium x serum P (Ca x
      P), are frequently elevated in end-stage renal disease patients on maintenance
      hemodialysis (HD). Elevated P and Ca x P have been associated with vascular
      calcification in dialysis patients. OBJECTIVE: [corrected] To examine the role of
      P and Ca x P as risk factors for incident peripheral vascular disease (PVD) in HD
      patients with pre-existing CVD. METHODS: This nested case-control study is drawn
      from the 11 incident PVD events reported in the cohort of the Secondary
      prevention with antioxidants of cardiovascular disease in end-stage renal disease
      (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and
      confirmed ultrasonographically. Each individual with a PVD event was matched for
      SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and
      gender with two individuals who had no CVD end point during the follow-up period.
      RESULTS: Serum P and Ca x P levels were significantly higher in PVD patients than
      in controls. In univariate logistic regression analysis, only serum P predicted
      PVD in this population (OR 2.02, 95% CI 1.07 - 3.81, p = 0.03). In multivariate
      analysis, adjustment was made for variables dissimilar by PVD status including
      underlying renal disease, diabetes, smoking, history of angina pectoris,
      prescription for vitamin D3, erythropoietin, calcium channel blockers and
      aspirin. In this model, serum P remained the only significant predictor of
      incident PVD (OR 2.4, 95% CI 1.01 - 5.74, p = 0.04). CONCLUSIONS: Findings of the
      present study are consistent with a role for serum P and Ca x P in the
      pathogenesis of PVD in HD patients.

PMID- 15730052
TI  - Hemodiafiltration with post-dilution reinfusion of the regenerated ultrafiltrate:
      a new on-line technique.
AB  - AIMS: All convective hemodiafiltration techniques require a replacement fluid,
      which must have an adequate electrolytic composition and must be sterile and
      pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be
      "regenerated" and used as a replacement fluid (hemo-filtrate reinfusion; HFR).
      The aim of this study was to evaluate whether the HFR technique as suggested in
      its original configuration could be improved by inverting the purification
      sequence (post-dilution HFR; PDHFR) in order to increase the purification
      efficiency of the whole system. METHODS: We performed standard HFR in 6 uremic
      patients during 6 months and, subsequently, during further 6 months, PDHFR. The
      dialytic efficacy of the two techniques and the filter blood loss were evaluated.
      Moreover, we studied how both techniques affected cytokine levels. RESULTS: We
      observed a significant increase of urea extraction and of Kt/V values in PDHFR.
      An equally significant improvement was observed in regard to the extraction of
      beta2-m and the blood loss. Furthermore, IL6 and TNFalpha decreased significantly
      after PDHFR treatment. CONCLUSIONS: HFR has proven to be an easy-to-perform
      hemodiafiltration technique, capable of resolving the typical problem of the
      other hemodiafiltration technique, the availability and production of a sterile
      and ultrapure reinfusion solution. The inversion of its configuration has allowed
      us to improve three aspects that have characterized, in our experience, the
      treatments performed in the original geometry: the removal of both urea and beta2
      m, and the filter. Finally, it's notable that the decrease in cytokines levels
      achieved with PDHFR might attenuate the uremic micro-inflammatory state.

PMID- 15730053
TI  - Anxiety and depression in chronic hemodialysis: some somatopsychic determinants.
AB  - AIMS: Depression and anxiety are so common in hemodialysis (HD) patients that we
      found it useful to study the respective contributions of the subjective somatic
      sensations and of the objective medical comorbidity to psychological distress. We
      also hypothesized that denial has a protective effect against anxiety and
      depression, and that alexithymia is, on the contrary, a risk factor. MATERIAL AND
      METHODS: In a cross-sectional design, we investigated relationships between
      psychological distress and somatic complaints, Charlson comorbidity index, denial
      and alexithymia, in a group of 54 patients on incenter HD. They filled
      psychometric self-rated questionnaires in (State Anxiety Inventory, Hospital
      Anxiety and Depression Scale, 13-item Short Beck Depression Inventory, Kidney
      Disease Quality of Life Short Form, 20-item Toronto Alexithymia Scale). A
      principal component analysis allowed us to focus on HADS-total score, which was
      confirmed to be representative of anxio-depression. Then, correlational analyses
      and a stepwise regression analysis were performed. RESULTS: HADS-total score is
      inversely associated with the use of denial as a psychological defence mechanism
      (p < 0.001), and positively correlated with difficulties in identifying emotions
      (p < 0.001), with difficulties in expressing feelings (p < 0.05), and with the
      intensity of subjective somatic complaints (p < 0.001). On the contrary, it is
      not related to the somatic comorbidity. In the stepwise regression, the somatic
      complaints, the denial and the difficulties in recognizing emotions emerge as the
      three main variables related to the HADS-total score (p < 0.001). CONCLUSIONS:
      Subjective physical complaints are here associated with psychological distress in
      chronic HD patients, while objective organic comorbidity does not seem to
      influence their mood and anxiety status. Denial is an efficient coping style
      against negative emotions, but it can diminish compliance. So, the subjective
      perception of the disease seems to have an important impact on the anxiety and
      mood levels, which can also be influenced by the emotional regulation abilities.

PMID- 15730054
TI  - Cellular and molecular mechanisms of secondary hyperparathyroidism.
AB  - The objective of this review is to share important basic research insights into
      the mechanisms of secondary hyperparathyroidism. An understanding of these
      mechanisms is essential to more effectively treating the disease. Central
      underlying abnormalities are increased parathyroid hormone (PTH) gene expression
      and secretion, and parathyroid cell proliferation. Significant progress has been
      made in understanding these abnormalities at the cellular and molecular level,
      particularly their regulation. Studies point to a prominent role of calcium,
      phosphate and vitamin D as regulators of PTH and parathyroid cell proliferation.
      1,25[OH]2 vitamin D3 decreases PTH synthesis and secretion. Small decreases in
      serum calcium and prolonged increases in serum phosphate as may occur in patients
      with chronic failure, increase PTH secretion, PTH gene expression, and
      parathyroid cell proliferation. Regulation at the level ofPTH gene expression is
      particularly significant given the limited amount of preformed mature PTH. It is
      now known that calcium and phosphate regulate PTH gene expression through changes
      in protective parathyroid cytosolic proteins that bind to an instability element
      in the PTH mRNA 3'-untranslated region and influence transcript stability. These
      findings may help guide the development of novel therapies for secondary
      hyperparathyroidism.

PMID- 15730055
TI  - Assessment of effects of lanthanum carbonate with and without phosphate
      supplementation on bone mineralization in uremic rats.
AB  - AIMS: Previous studies have indicated that impaired bone mineralization in 5/6 th
      nephrectomized rats given high doses of lanthanum carbonate is due to phosphorus
      depletion caused by excessive binding to, and reduced absorption of, dietary
      phosphate. This study aimed to test this hypothesis by: 1) directly comparing the
      effects of a supratherapeutic dose of lanthanum carbonate or dietary phosphorus
      restriction on bone mineralization in a rodent model of chronic renal failure
      (CRF); and 2) investigating whether phosphorus supplementation would prevent the
      bone mineralization defect associated with lanthanum carbonate treatment. METHODS
      AND MATERIALS: Male Sprague-Dawley rats were subjected to sham surgery or a two
      step 5/6th nephrectomy to induce CRF and randomized across five treatment groups:
      sham, CRF, CRF + dietary phosphorus deficiency, CRF + lanthanum carbonate (1000
      mg/kg/ day), and CRF + lanthanum carbonate + parenteral phosphorus repletion.
      RESULTS: Rats with 5/6th nephrectomy had elevated serum creatinine, blood urea
      concentration, and urine volume and protein, consistent with impaired renal
      function, and increased urinary phosphorus and serum parathyroid hormone,
      consistent with hyperparathyroidism. Lanthanum carbonate and dietary phosphate
      insufficiency induced parallel changes in serum and urine markers of phosphate
      homeostasis and increased osteoid formation. These changes induced by lanthanum
      carbonate were normalized by systemic phosphate supplementation. CONCLUSIONS:
      These findings provide further support for the concept that supratherapeutic
      doses of lanthanum carbonate induce effects on bone mineralization in uremic rats
      via an indirect pharmacological mechanism (phosphate depletion) and not via
      direct bone toxicity.

PMID- 15730056
TI  - Utilization of bone histomorphometry in renal osteodystrophy: demonstration of a
      new approach using data from a prospective study of lanthanum carbonate.
AB  - AIM: The aim of this study was to develop a novel approach to the analysis of
      bone histomorphometric data and outcomes presentation that would simplify the
      characterization of renal osteodystrophy and facilitate clinical decision-making.
      METHODS AND MATERIALS: Data were derived from a randomized trial of dialysis
      patients treated for one year with a dose of lanthanum carbonate or calcium
      carbonate (up to 3750 mg/day and 9000 mg/day, respectively). Histomorphometric
      analyses of baseline and end-of-study bicortical transiliac bone biopsies were
      performed. Activation frequency, bone formation rate/bone surface, osteoclast
      surface/ bone surface, osteoblast surface/bone surface, mineralization lag time,
      and osteoid thickness were determined to provide a measure of overall bone cell
      activity (bone formation, bone resorption, bone turnover) and risk of developing
      osteopenia (bone balance). A novel approach of qualitatively grouping these
      numerical data as "improved", "unchanged", or "worsened" based on deviation from
      normal was used to facilitate interpretation of clinical relevance. RESULTS:
      Using our method, lanthanum carbonate was shown to improve histomorphometric
      parameters measured. These improvements were superior to those produced by
      calcium carbonate. These data add valuable clinical relevance to the previously
      published qualitative data from the same cohort [D'Haese et al. 2003]. Lanthanum
      carbonate moderated extreme forms of renal osteodystrophy, whereas calcium
      carbonate treatment increased the incidence of adynamic and predominant
      hyperparathyroid bone disease. CONCLUSIONS: This study provides an approach to
      the prospective evaluation of bone disease progression with therapy, and its
      application supports the safety and greater efficacy of one-year lanthanum
      carbonate versus calcium carbonate therapy as a means to normalize bone turnover
      in dialysis patients.

PMID- 15730057
TI  - Mechanisms of vascular calcification in renal disease.
AB  - Vascular calcification is commonplace in patients with end-stage renal disease
      where it develops rapidly and predicts a variety of adverse outcomes. The
      processes responsible for vascular calcification have been the focus of much
      research, aided in recent decades by molecular genetic techniques and in vitro
      models. Converging evidence now suggests that vascular calcification is an
      active, regulated process, with abundant similarities to the process of skeletal
      mineralization. Using an in vitro model of calcifying vascular smooth muscle
      cells (VSMCs), we have shown that a mineral imbalance induces VSMC apoptosis, and
      that VSMC apoptotic bodies and vesicles can nucleate basic calcium phosphate in
      the form of hydroxyapatite, the same mineral found in bone. Gene expression
      studies suggest that the normal vessel wall expresses proteins such as matrix Gla
      protein that inhibit calcification. In addition, circulating proteins such as
      fetuin-A are produced at remote sites and act to inhibit soft tissue
      calcification systemically. However, down-regulation or perturbation of these
      proteins may lead to a phenotypic transformation of VSMCs to osteo/chondrocytic
      like cells while the calcified environment may stimulate macrophages to adopt
      osteoclastic properties. Both clinical and basic research findings indicate an
      inverse relationship between bone mineralization and vascular calcification. The
      mechanisms linking these two processes are a topic for further investigation,
      with current theories proposing a role for lipids, common regulatory molecules,
      and calcium and bone turnover. We have synthesized these findings into a
      theoretical model offering a putative pathway for the development of severe
      vascular calcification in end-stage renal disease.

PMID- 15730058
TI  - Contrasting mammalian PTH promoters: identification of transcription factors
      controlling PTH gene expression.
AB  - Parathyroid hormone (PTH) is a key component in the maintenance of calcium and
      phosphate homeostasis. The steady-state expression of the PTH gene can be modeled
      as a balance between transcriptional activators and repressors. During renal
      failure, the gradual loss of kidney function is often accompanied by increased
      circulating concentrations of PTH and decreased synthesis of 1,25-di
      hydroxyvitamin D3 (1,25(OH)2D3). The latter finding results in impaired calcium
      absorption and the removal of a known repressor of PTH gene transcription.
      Current regimens for treating secondary hyperparathyroidism associated with renal
      insufficiency are focused on boosting activities that repress PTH gene
      transcription or secretion of the hormone, and involve the use of vitamin D and
      its analogues or calcimimetic agents. However, in recent years, concerns have
      arisen over the use of the steroid hormone and alternative treatments are being
      sought. Here, we present new information regarding transcription factors
      controlling PTH gene expression, which include the specificity proteins (Sp) and
      the nuclear factor Y (NF-Y) complex. A highly conserved DNA response element for
      the Sp proteins has been identified in mammalian promoters, while an NF-Y binding
      site is uniquely positioned in the human promoter. Both of these factors are
      expressed in the parathyroid gland and their DNA elements appear to be
      functioning as activators of PTH gene expression. Further elucidation of such
      pathways may offer novel approaches for treating hyperparathyroidism associated
      with renal failure via suppression of transcriptional activators. That work is
      currently in progress.

PMID- 15730059
TI  - Spontaneous rupture of a left gastroepiploic artery aneurysm in a patient with
      autosomal-dominant polycystic kidney disease.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) has been known to be
      associated with a variety of vascular diseases. We present a hemodialysis patient
      with ADPKD who died of a massive intraperitoneal hemorrhage caused by the
      spontaneous rupture of a left gastroepiploic artery aneurysm. A 64-year-old male
      was admitted to our hospital with acute upper abdominal pain and hemorrhagic
      shock. An abdominal angiography showed three aneurysms and the source of
      hemorrhage was assumed to be the left gastroepiploic artery aneurysm. The patient
      died of severe metabolic acidosis and disseminated intravascular coagulation
      (DIC) on the second hospital day. At autopsy, there was massive bleeding into the
      abdominal cavity, and pathological examination of the left gastroepiploic artery
      aneurysm revealed a dissecting aneurysm. This is the first case describing a
      rupture of a gastroepiploic aneurysm in a patient with ADPKD.

PMID- 15730060
TI  - Hypercreatininemia and hyperglycemia: diabetic nephropathy or "inverted
      peritoneal auto-dialysis"?
AB  - We describe a case of 51-year-old male with fever, abdominal pain and inguino
      scrotal hernia. Laboratory examination revealed hypercreatininemia and
      hyperglycemia, firstly interpreted as diabetic nephropathy. US and CT scan showed
      a hernia of the bladder into the scrotum. Surgery revealed multiple bladder
      perforations with peritoneal diffusion of urine. So, hypercreatininemia was
      caused by peritoneal reabsorption of urea and creatinine, a condition that may be
      described as "inverted peritoneal auto-dialysis". Surgical reposition and
      repairment of the bladder led to rapid normalization of serum urea and
      creatinine. Discharged diagnosis was intraperitoneal rupture of inguino-scrotal
      hernia of the bladder in patient with recent onset of diabetes mellitus.

PMID- 15730061
TI  - Spontaneous remission in frequently relapsing minimal-change disease.

PMID- 15730062
TI  - Nephrotic syndrome associated with hidradenitis suppurativa.

PMID- 15730063
TI  - Psychological consequences of the 1999 earthquake in Turkey.
AB  - We explored the prevalence of posttraumatic stress disorder (PTSD) and its
      relation to demographic characteristics and other risk factors for developing
      PTSD in a large sample (N = 910) of earthquake survivors living in tent city.
      Twenty-five percent of the sample met DSM-IV criteria for PTSD assessed with the
      Posttraumatic Stress Disorder Self Test (PTSD-S). Peritraumatic factors explained
      the most variance when the risk factors were grouped as demographics,
      pretraumatic, peritraumatic, and posttraumatic. The study emphasized that PTSD
      among the earthquake victims was as prevalent in Turkey as after disasters in
      other developing countries but higher than usually found after disasters in
      developed countries, and there was a relation between some factors-mostly
      peritraumatic-and PTSD.

PMID- 15730064
TI  - Imagery vividness and perceived anxious arousal in prolonged exposure treatment
      for PTSD.
AB  - The present paper examines imagery vividness and anxiety during Prolonged
      Exposure (PE) for chronic PTSD among 69 female survivors of sexual or nonsexual
      assault. All participants received between 9 and 12 individual sessions of either
      PE alone or in combination with cognitive restructuring. As hypothesized,
      vividness and anxiety ratings from early imaginal exposure sessions were
      moderately to highly correlated, but these correlations decreased in later
      sessions. Both subjective distress and vividness decreased significantly with
      exposure. Greater reductions in subjective distress between the first and last
      exposure session were related to better outcome. However, contrary to hypothesis,
      vividness was not related to outcome. Theoretical implications of the results are
      discussed.

PMID- 15730065
TI  - Are avoidance and numbing distinct PTSD symptom clusters?
AB  - We present the conceptual basis and empirical evidence for considering avoidance
      and numbing as distinct posttraumatic stress disorder (PTSD) symptom clusters.
      The majority of data from factor analytic studies supports the position that
      avoidance and numbing are distinct symptom clusters. As well, the available data
      suggest that (a) different treatment modalities have differential effects on
      reducing avoidance but not numbing, (b) patients with more severe pretreatment
      numbing have poorer treatment outcomes, (c) avoidance and numbing have different
      patterns of correlation with depression, and (d) they have different correlations
      with physiological indices of attention. We conclude that avoidance and numbing
      are distinct PTSD symptom clusters. This distinction has implications for
      revising current diagnostic criteria. The recognition of this distinction may
      lead to advances in understanding and treating PTSD.

PMID- 15730066
TI  - Clinical correlates of poor sleep quality in posttraumatic stress disorder.
AB  - Sleep disturbances (SD) are a core clinical feature of PTSD. The goal of the
      study was to determine the influence of patient-related characteristics, disorder
      related characteristics, and psychiatric comorbidity on the severity of SD in
      PTSD outpatients (n = 367) who were not recruited for a sleep study. Increased
      severity of SD paralleled increasing overall PTSD severity. The severity of SD
      did not differ according to gender, age groups, types of trauma, PTSD chronicity,
      or psychiatric comorbidity. Results suggest that age, gender, and psychiatric
      comorbidity have minimal impact on sleep quality in this PTSD sample. The
      inclusion of PTSD patients who were not specifically seeking treatment for SD
      reinforces the study findings.

PMID- 15730067
TI  - Integration of psychological and biological approaches to trauma memory:
      implications for pharmacological prevention of PTSD.
AB  - Although memory processes play a central role in both psychological and
      neurobiological accounts of the development of posttraumatic stress disorder
      (PTSD), there has been little integration of the two literatures. This paper aims
      to consider the implications of an integrated account of trauma memory for
      pharmacological treatments that have been proposed for the prevention of PTSD.
      The idea of reprocessing trauma memories to bring about recovery, central to the
      psychological account of PTSD, is translated into terms more familiar in the
      biological literature using the concept of reconsolidation of active memories. It
      is suggested that physiological arousal enhances the reprocessing of trauma
      memories. Drugs that influence arousal may have effects after trauma which depend
      on the psychosocial context, helping to prevent the development of PTSD in some
      trauma victims, but impeding recovery in others who would do well without
      treatment.

PMID- 15730068
TI  - Comparison of the posttraumatic stress disorder scale versus the clinician
      administered posttraumatic stress disorder scale in domestic violence survivors.
AB  - The posttraumatic diagnostic scale (PDS) is a self-report instrument for PTSD
      that is simple to administer and has demonstrated good psychometric properties.
      We compared the PDS with the gold standard clinician administered PTSD scale
      (CAPS) diagnostic interview for PTSD. We assessed 138 women who were victims of
      domestic violence using both the PDS and the CAPS. Findings confirmed that PTSD
      develops at a high base rate in this sample. The PDS generally performed well in
      relation to the CAPS although with a tendency to overdiagnose PTSD. The findings
      lend further support to the use of the PDS as a diagnostic tool for PTSD but
      indicate that it is better at identifying survivors with PTSD than those without
      the disorder.

PMID- 15730069
TI  - Development and psychometric validation of a Domestic Violence Coping Self
      efficacy Measure (DV-CSE).
AB  - Psychometric properties of a Domestic Violence Coping Self-Efficacy Measure were
      examined. Two-hundred eighty three women assaulted within the past 6 months were
      recruited. Internal reliability of the measure was very good (alpha = .97).
      Principle components factor analysis indicated one primary factor accounting for
      56% of the variance. The measure was positively associated with optimism,
      adaptive coping, and healthy psychological functioning, and negatively associated
      with trauma-related distress, negative mood, and maladaptive coping. A small
      positive association with social desirability was found. This measure may have
      significant clinical utility in helping survivors by indicating areas where
      individuals feel especially vulnerable or empowered.

PMID- 15730070
TI  - Posttraumatic stress disorder among deliberate self-poisoning patients.
AB  - This study explored posttraumatic stress disorder (PTSD) among suicide
      attempters. Participants were 330 hospital-treated deliberate self-poisoning
      (DSP) patients. Twelve-month prevalence of PTSD and comorbid psychiatric
      disorders was determined using the Composite International Diagnostic Interview
      (CIDI-A). Standard disability measures and demographic information were also
      obtained. PTSD prevalence was 32% among women and 15% among men. The PTSD group
      had significantly higher levels of affective disorder, anxiety disorders other
      than PTSD, psychiatric disability, and service utilization than DSP patients
      without PTSD. Logistic regression modeling showed that PTSD was associated with
      the type of traumatic event, number of events, affective disorder, and anxiety
      disorder other than PTSD.

PMID- 15730071
TI  - Effects of violence exposure and daily stressors on psychological outcomes in
      urban adolescents.
AB  - Relations between adolescent violence exposure, daily stress, and psychological
      outcome were examined. Parent/adolescent dyads (N = 80) completed questionnaires,
      which included parent ratings of adolescent externalizing and internalizing
      problems and adolescent self-ratings of emotional adjustment. Severity of daily
      stress moderated the relation between levels of violence exposure and extent of
      adolescent externalizing and internalizing problems. The relation was significant
      at higher levels of daily stress, but nonsignificant at lower levels of stress.
      In contrast, daily stress did not emerge as a moderator in the relation between
      violence exposure and adolescent emotional adjustment. Results suggest that
      adolescents experiencing high levels of violence exposure and daily stress should
      be considered at great risk for poor psychological outcome.

PMID- 15730072
TI  - Is it an accident? Recurrent traumatic life events in level I trauma center
      patients compared to the general population.
AB  - The trauma history screen developed for the National Comorbidity Survey (NCS) was
      used to assess prior trauma in a representative sample of injured acute care
      inpatients (n = 251). Adjusted logistic regressions compared the trauma histories
      of intentionally (n = 66) and unintentionally (n = 185) injured patients with NCS
      participants (n = 5873). Whereas only 11% of NCS respondents reported 4 or more
      lifetime traumas, 61% of intentionally injured patients (Adjusted OR = 7.97, 95%
      CI = 4.33, 14.68) and 40% of unintentionally injured patients (Adjusted OR =
      4.26, 95% CI = 2.94, 6.16) reported 4 or more lifetime traumas. In adjusted
      analyses, inpatients were at increased risk for reporting all types of trauma
      except combat. Screening and intervention procedures that address the unique
      characteristics of this high-risk patient population are needed in the acute care
      setting.

PMID- 15730073
TI  - Preliminary evaluation of a video-based intervention for older adult victims of
      violence.
AB  - The present study evaluated a brief, video-based intervention for older adults
      designed to: provide psychological education regarding common reactions to crime;
      offer information about healthy coping strategies to manage crime-related
      symptomatology; and increase awareness of effective safety planning strategies.
      Following reporting to police, 116 older adult crime victims were randomly
      assigned to receive either standard advocate-based services plus the video-based
      intervention or standard advocate services alone. Results indicated that older
      adult victims assigned to the video condition and assessed later that day
      exhibited greater awareness of crime-related symptoms, healthy coping strategies,
      and safety planning strategies than did the older adult victims assigned to
      standard practice of care. However, despite knowledge gains, and in contrast to
      our predictions, no differences on measures of anxiety or depression were evident
      between the treatment conditions at 6-week follow up.

PMID- 15730074
TI  - A new development in PTSD and the law: the case of Fairfax County v. Mottram.
AB  - The decision of the Virginia Supreme Court in Fairfax County Fire & Rescue
      Department v. Mottram (2002) has important implications for Workers' Compensation
      claims for posttraumatic stress disorder, particularly those involving emergency
      services personnel. A firefighter/paramedic who developed chronic, disabling PTSD
      after responding to a fatal fire was denied benefits because he had previously
      reported symptoms of the disorder, whereas the statute recognized a single
      traumatic incident only. The court held that PTSD resulting from multiple
      traumatic stressors may be considered a compensable occupational disease
      analogous to dermatitis developed by a flower shop employee with chronic exposure
      to irritating stimuli. The decision, which constitutes legal recognition of work
      related cumulative PTSD in rescue workers, provides benefits for treatment and
      encourages earlier treatment of traumatic stress in this group.

PMID- 15730075
TI  - [Meta-analysis of the Italian studies on short-term effects of air pollution-
      MISA 1996-2002].
AB  - INTRODUCTION: the Italian Meta-analysis of short-term effects of air pollution
      for the period 1996-2002 (MISA-2) is a planned study on 15 Italian cities, among
      the larger country towns summing up 9 millions and one hundred thousand
      inhabitants at 2001 census. HEALTH OUTCOMES DATA: mortality for all natural
      causes (362254 deaths), for respiratory causes (22317) and cardiovascular causes
      (146830), and hospital admissions for acute conditions, respiratory (278028
      admissions), cardiac (455540) and cerebrovascular (60960), have been considered.
      Mortality data came from Regional or Local Health Unit Registries, while hospital
      admissions data have been selected from Regional or Hospital Archives (exclusion
      percentages range for all admissions between 45% and 82%). For each participating
      city daily series averaged about 4.3 years, with a minimum of three consecutive
      years. AIR POLLUTANTS DATA: daily pollutants concentration series (SO2, NO2, CO,
      PM10, O3) came from air quality monitoring networks of Regional Environmental
      Protection Agencies, of Environmental Offices of Provinces or Municipalities.
      Monitors' selection has been done by a working group composed by representatives
      of monitoring network Agencies. The selection criteria are the representativeness
      of general population exposure for each specific pollutant, avoiding as possible
      monitors close to high traffic roads; and the number, quality and location of
      monitors, selecting around 3-4 monitors with continuous data flow in the period
      (at least 75% of valid hourly data). The final series has been created averaging
      over monitors and imputing missing values under proportionality assumptions.
      Median of Pearson correlation coefficients between pairs of monitors of the each
      city was 0.62, interquartile range 0.42-0.77. STATISTICAL METHODS: A generalized
      linear model on daily counts of health events has been fitted for each city.
      Linear pollutant effect has been specified and bi-pollutant models have been
      fitted for PM10+NO2 and PMO+O3. Temperature has been modelled parametrically
      using a change point at 21 degrees C and lagged effects. Humidity, day of the
      week, national holidays and influenza epidemics (using data from the National
      Surveillance Programs from 1999) are the other considered confounders. An age
      specific natural cubic spline on season has been specified with 5 degree of
      freedom (on average) per year for mortality and 7 degree of freedom per year for
      hospital admission data. The base model is age-stratified (0-64, 65-74, 75+
      years). Gender, age, season specific models have been fitted, too. Five
      sensitivity analyses have been done, varying the degree of freedom for the
      seasonality spline and specifying non parametric functions on temperature.
      Constrained distributed lag models have been fitted on mortality data to study
      potential harvesting effects. City-specific results have been meta-analyzed by
      random effects hierarchical Bayesian model. Four different models have been
      fitted in the sensitivity analyses, assuming different priors on heterogeneity
      variance and outlier-resistant prior on city-specific effects. Bayesian meta
      regressions have been fitted on base model, bi-pollutant and season-specific city
      specific results. Attributable deaths have been estimated by Monte Carlo methods
      using effect, pollutant, baseline rate distributions. Fourteen different
      scenarios have been considered for PM10 and ten for NO2 and CO, using meta
      analitic and posterior city-specific effect estimates RESULTS: Pollutants effects
      are reported as percent increase on mortality or hospital admissions for an
      increase of 10 microg/m3 of SO2, NO2 and PM10, and 1 mg/m3 of CO. We found an
      increase on mortality for all natural causes associated to increase of air
      pollutants concentration (for NO2 0.6% 95%CrI 0.3,0.9; CO 1.2% 0.6,1.7; PM10
      0.31% -0.2,0.7). Similar findings were found for cardiorespiratory mortality and
      hospital admissions for respiratory and cardiac diseases. We found no difference
      by gender. There was a weak evidence of greater effect size in extreme age groups
      (0-24 months and over 85 years where we found a percent increase in mortality for
      all natural causes for PM10 of 0.39% CrI95% 0.0,0.8). There was a strong evidence
      for each pollutant of greater effects in the warm season (1st May-30th September)
      on mortality and hospital admissions (we found a percent increase in mortality
      for all natural causes for PM10 in the warm season of 1.95% CrI95% 0.6,3.3). The
      associations between pollutants concentration and health events were present at
      different time lags, depending on outcome and exposure. For mortality, the excess
      risk peaked within few days from the exposure increase (two days for PM10, up to
      four days for NO2 and CO). Mortality displacement was minor and ended within two
      weeks. Cumulative effects at fifteen days showed higher risks for respiratory
      diseases (PM10 1.65% CI95% 0.3,3.0). The results of meta-regressions showed
      associations between PM10 effects on mortality and hospital admissions, and
      mortality for all causes (SMR) and PM10/NO2 ratio. The effect modification of
      temperature was very consistent, and also using bi-pollutant models. Such effect
      modification was greater during the cold season. We found and overall impact on
      mortality for all natural causes in the period 1996-2002 between 1.4% and 4.1% of
      all deaths for gaseous pollutants (NO2 and CO). The estimates were more imprecise
      for PM10, due to the variability among cities of the effect estimates (0.1%;
      3.3%). The limits stated in the European Union directives for 2010 would have
      been saved about 900 deaths (1.4%) for PM10 or 1400 deaths for NO2 (1.7%) among
      all the MISA cities, applying posterior city-specific effect estimates.

PMID- 15730076
TI  - Stem cell research, politics, and bioethics.

PMID- 15730077
TI  - Horses, zebras, and CPCs.

PMID- 15730078
TI  - Stem cell research: the fallacy in Bush's position.

PMID- 15730079
TI  - Deinstitutionalization of the mentally ill. Policy triumph or tragedy?

PMID- 15730080
TI  - A twenty-eight-year-old female with right shoulder pain.

PMID- 15730081
TI  - Opinion: quality makes good business sense.

PMID- 15730082
TI  - Isotretinoin therapy: any need for laboratory assessment?
AB  - BACKGROUND: Recently studies showed the no need for laboratory follow up of
      patients on isotretinoin therapy. The aim of this study is to assess this issue.
      PATIENTS AND METHODS: A retrospective study on-400 patients was performed to
      analyze the laboratory data before and after isotretinoin therapy of acne
      vulgaris patients. All patients received isotretinoin at a dose of 1mg/kg for 20
      weeks. RESULTS: AST was elevated in 25/400(6.25 %), ALT was elevated in
      10/400(2.5 %). Cholesterol was elevated in 55/400(13.75%). Triglycerides were
      elevated in 20/400(5 %). CONCLUSION: This study supports the previous evidence
      for the no need for performing laboratory investigations for patients on
      isotretinoin therapy.

PMID- 15730083
TI  - Antityphoid agglutinins in African school aged children with malaria.
AB  - BACKGROUND: Salmonella antibodies are known to cross-react with other antigens
      including those from Escherichia coli. Malaria antigens may also have similar
      characteristics. OBJECTIVES: To establish antibody levels in malaria patients and
      controls and to decipher (if any), relationship(s) between significant agglutinin
      responses to the various antigens as outcome factor and malaria parasitaemia as
      exposure factor. STUDY SETTING: University of Benin Teaching Hospital and Egor
      Local Government Area of Edo state, Nigeria, between July and August, 1999. STUDY
      DESIGN: Prospective and a case control study. PATIENTS AND METHODS: Agglutinins
      against H and O antigens of Salmonella typhi, Salmonella paratyphi A, B and C
      were determined using the Widal test in 189 school aged children(5-16 years) with
      malaria (males, 54.0%; females, 46.0%) and 175 apparently healthy children,(52.0%
      males, and 48.0 %) of comparable age and gender distributions. Agglutination
      reaction at >1.80 were significantly more in malaria patients (52/189 or 27.5%)
      than in controls (28/175 or 16.0%) (x2 = 7.07; p<0.05). Agglutination reaction to
      various antigens were significantly higher in controls with malaria parasitaemia
      (10/36 or 27.8%) than those without parasitaemia (18/139 or 12.9%) (x2 = 4.57;
      p<0.02) (OR=2.59). Significant titres were also more in subjects and controls
      with malaria parasitaemia (62/235 or 26.38%) than in those without (18/139 or
      12.94%) (x2=9.32; p< 0.05) (OR=2.41). At dilution of > or =1.80 children aged 9 
      14 years (as compared to those < or =8 years of age) and more males (subjects and
      controls) had demonstrable agglutinins. At most serum dilutions, antibodies to H
      antigens were more commonly found in subjects and controls than agglutinins
      against O antigen of Salmonella typhi. Fifty percent of subjects and controls had
      demonstrable agglutination at approximate dilutions of 1:60 and 1:40
      respectively. The number of subjects and controls that showed demonstrable
      agglutinins against Salmonella paratyphi antigens were less than 10.0%
      CONCLUSION: Enhanced agglutinin to DO and DH may be a phenomenon associated with
      childhood malaria.

PMID- 15730084
TI  - Pattern of head and neck malignant tumours in a Nigerian teaching hospital--a ten
      year review.
AB  - BACKGROUND: In Nigeria record of incidence and pattern of Head and Neck
      malignancies is scanty. In our Hospital, there had been no prior published report
      on this subject. OBJECTIVE: To study the pattern of occurrence of Head and Neck
      malignancies treated in Obafemi Awolowo university Hospitals Complex, Ile Ife,
      Nigeria. METHODS: medical records of patients with histopathologically confirmed
      head and neck malignancies over a 10 year period (1989--1998) were analyzed. MAIN
      RESULTS: Three hundred and thirteen (313) cases, made up of 184 (59%) males and
      129 (41%) females were found. The most common sites for head and neck
      malignancies were found to be in the oral cavity (36.8%), the neck (26.8 %), the
      thyroid (13.7 %), and the esophagus (5.1%). The paranasal sinuses and the ear
      were the least affected anatomical sites with one (0.3 %) of cases each. The
      histopathological tumour types found in this work were lymphoma (40.26%),
      squamous cell carcinoma (25.23%), sarcoma (2.6%), while many other minor
      histopathological variants accounted for 31.9%. Lymphoma was the most common in
      children, while carcinoma was found in, and forms the most common
      histopathological variant of head and neck malignancies in the older age group.
      PRINCIPAL CONCLUSIONS: There is a high incidence of childhood head and neck
      malignancies found in this study in contrast to the Western literature where the
      highest incidence is found in the older age group and the elderly. Jaw
      malignancies constituted the most common malignancies of the oral cavity.
      Lymphoma and thyroid malignancies are relatively common in our center.

PMID- 15730086
TI  - Plasma and semen ascorbic levels in spermatogenesis.
AB  - BACKGROUND: Conflicting reports on the mechanism of action of ascorbic acid level
      in male reproductive system exist and very little is known about the ascorbic
      acid status in Nigerian males with weak fertility. METHOD: Ascorbate that
      accumulates preferentially in the testis, the lipid and lipoprotein levels were
      determined in the plasma of Nigerian males. Twenty-seven (27) male with
      inadequate spermatogenesis (36+/-1.0) years, with mean value of 15.6+/-6.90
      million/cm3 sperm count and fourteen (14) controls (34+/-0.6) years, with mean
      value of 108.0+/-25.42 million/cm3 sperm count were selected for this study. The
      anthropometric indices were also determined. RESULTS: There were highly
      significant decreases in sperm cell count, percentage motility and percentage
      vitality (p<0.001) in each case, while percentage morphologically abnormal sperm
      cells was significantly elevated (p<0.001) compared with the control values.
      There were significant decreases in the seminal and plasma ascorbic acid
      concentrations (p<0.001) in the males who had inadequate spermatogenesis compared
      with the control values. The plasma total cholesterol (TC) and body mass index
      (BMI) were not significantly different from the corresponding control values, but
      the plasma low density lipoprotein (LDLC) (p<0.001) and triglyceride (TG)(p<0.01)
      concentrations were significantly increased in all the patients. While the plasma
      high density lipoprotein cholesterol (HDLC)(p<0.001) was significantly decreased
      compared with the controls. The plasma lipid and lipoprotein levels did not
      demonstrate any definite pattern with the sperm characteristics. CONCLUSION: The
      decreased semen ascorbate level may play a significant role in the reduced sperm
      characteristics in these patients.

PMID- 15730085
TI  - Computerised tomographic detection of intracranial complications of paranasal
      sinus infections.
AB  - Ninety-four patients were referred for CT examination of the paranasal sinuses
      within a five year period. Only 11 (11.7%) of them had intracranial
      complications. These include cerebral, subdural and epidural abscesses, frontal
      bone osteomyelitis. The maxillary and ethmoidal sinuses were mostly involved and
      can be implicated as the sinogenic causes of intracranial infections. Sphenoidal
      sinus was not involved in any of the patients.

PMID- 15730087
TI  - The pattern of paediatric burn injuries in Southwestern, Saudi Arabia.
AB  - BACKGROUND: Burn injuries constitute a major concern in the paediatric age group
      with respect to morbidity and mortality particularly among children in developing
      countries. Burn injuries represent an extremely stressful experience for both the
      burn victims as well as their families. OBJECTIVES: To identify the pattern and
      demographic aspects of paediatric burn injuries (BI) at the Aseer Central
      Hospital, Abha, Kingdom of Saudi Arabia and to analyze morbidity and mortality as
      such information has not been reported from our locality. PATIENTS AND METHODS:
      All the 380 patients children aged <1 to 12 with BI admitted to the Burns Unit
      over six year period (January 1997--December 2002) of the Aseer Central Hospital
      Saudi Arabia. A special proforma was designed and the information entered
      included age, sex, residence, level of education, place and time of BI, brief
      description of the event, agent, and site(s) affected, total surface area burnt
      (TSAB), degree, depth, severity, date of admission and discharge. RESULTS: Out of
      380 patients in this study, 191 (50.3%) were boys and 189 (49.7%) were girls (M:F
      = 1.01:1). There was no statistical difference in the gender distribution
      (p=0.4). Saudi and non-Saudi patients constituted 362 (95.3%) and 18 (4.7%).
      Ninety (24%) were aged one year or below, 204 (54 %) included children older than
      one year but not older five years of age and 86 (22 %) were above five years of
      age but not older than 12 years. Whereas 64% of BI are due to scald, 27.6% were
      due to flame, 5 % were due to electrical while 1.8 % were due to chemical injury.
      CONCLUSION: The majority of BI occur in children aged five years and below and
      most of these injuries occurred at home. Scald injuries predominated and length
      of hospital stay correlated well to the extent of burned body surface area.

PMID- 15730088
TI  - Clinical spectrum of herpes zoster in HIV-infected versus non-HIV infected
      patients in Benin City, Nigeria.
AB  - BACKGROUND: Herpes zoster is due to reactivation of the varicella-zoster virus
      (VZV) at the sensory nerve ganglia. Some reports indicate that there might be
      differences in the pattern of presentation of herpes zoster in HIV infected
      patients. The objective of this study therefore, is to compare the clinical
      spectrum of herpes zoster in HIV-infected versus non-HIV infected patients. STUDY
      DESIGN: In this prospective study all patients presenting with clinical features
      of Herpes zoster had serological test (ELISA) for Human immunodeficiency viral
      (HIV) antibodies done and confirmed by the Double/Triple test algorithm. They
      were examined clinically to determine the dermatome(s) involved, the severity of
      the disease and the presence of any complication. The patients were categorized
      according to their HIV-status for the purpose of statistical analysis. RESULTS:
      Fifty-two out of the seventy-three patients seen during the study period were
      evaluated: 22 male (42.3 %) and 30 female (57.7 %) patients. Thirty-six (69.2 %)
      patients were HIV-positive while 16 (30.8%) were HIV-negative. The age
      distribution of the patients was bimodal; the mean age of patients in the HIV
      positive group was 36.1+/-16.14 years while that of the HIV-negative group was
      56.3+/-17.51 years. Multidermatomal involvement, affectation of the Trigeminal
      nerve dermatome and the presence of systemic symptoms such as fever and weakness
      correlated significantly with the presence of HIV infection. Mean times to
      cessation of new vesicle formation, crusting, and resolution of zoster-associated
      pain were also significantly longer in the HIV-positive patients. There were no
      statistically significant differences in the incidence of post-herpetic
      neuralgia, keloids, and bacterial super-infection in both groups. CONCLUSION:
      Herpes zoster was generally more severe in the presence of HIV infection.

PMID- 15730089
TI  - Primary head and neck cancers in North Eastern Nigeria.
AB  - BACKGROUND: To document the pattern of primary head and neck cancers in North
      Eastern Nigeria. STUDY DESIGN: A record-based study of primary head and neck
      cancers histologically diagnosed at the University of Maiduguri Teaching Hospital
      (UMTH), Maiduguri, North Eastern Nigeria between 1987 and 2002. RESULTS: A total
      of 317 cases (20 cases per year) were diagnosed. The most common cancer sites
      were the oral cavity (15.1%) and nasopharynx (11.7%). Carcinomas (68.4 %) were
      the most common cancers reported, mostly affecting the oral cavity (20.3%).
      Carcinomas were associated with farmers, kola nut chewers and tobacco users in
      this region, while kaposi sarcoma was the only cancer associated with HIV
      positive patients. The overall mean duration of symptoms for cancers was 29.1+/
      62.2 months. The mean duration for carcinomas was longer than for sarcomas
      (p>0.05) and lymphomas (p= 0.05). 81 % of the staged cancers reported in the
      stage IV; while treated cancers required primary radiotherapy (51 %) or an
      adjuvant radical surgery and chemotherapy (9.4%). CONCLUSION: Intra-oral
      carcinomas were the most common histological types of cancers in the head and
      neck. The delay before and the cancer stage at presentation may be due to the
      lack of cancer management facilities and manpower in most of the hospitals in the
      region.

PMID- 15730090
TI  - Childhood intestinal obstruction in Northwestern Nigeria.
AB  - BACKGROUND: Intestinal obstruction is a common cause of childhood surgical
      emergency in the tropics. The aim of this paper was to assess the pattern and the
      outcome of mangement of intestinal obstruction in Nigerian children. STUDY
      DESIGN: The clinical reccords of all the cases of childhood intestinal
      obstructions managed at a teaching hospital in northwestern Nigeria between 1999
      and 2003 were retrospectively reviewed. RESULTS: There were 54 children, 44(81.5
      %) were boys and 10 (8.5 %) were girls (m:f=4.4:1). Fifteen (27.8%) and 22
      (46.2%) were neonates and infants, respectively. The causes of the intestinal
      obstruction were intussusception 16(29.6 %), Hirschprung's disease 14(25.9%),
      anorectal anomaly 12 (22.2%), external hernias 6(11.1%), atresia 5(9.3%) and
      congenital bands 1(1.9 %). The clinical features were consistent with those
      reported from other parts of the world, except that many patients with
      intussusception presented late with gangrenous intestines. The overall mortality
      was 6(11.1 %); the mortality in the neonates was 5(33.3 %). CONCLUSION: Apart
      from the obvious absence of worm infestation, the aetiological pattern and the
      clinical presentation of childhood intestinal obstruction in this study agrees
      with those reported from other parts of the country. Their management is
      associated with high mortality in our environment, especially when there are
      associated anomalies or the presentation is late.

PMID- 15730091
TI  - Cancer of the cervix in Ilorin, Nigeria.
AB  - OBJECTIVE: The purpose of this study is to review our experience with carcinoma
      of the cervix in Ilorin, Nigeria. METHOD: From 1st January 1990 to 31st December
      1999, a total of 169 cases of invasive cervical cancer wereseen at the Department
      of Obstetrics and Gynaecology of the University of Ilorin Teaching Hospital,
      Ilorin, Nigeria. RESULTS: Carcinoma of the cervix accounted for 63.1 % of
      histologically confirmed gynaecological cancers. Most of the patients were
      married 147 (98.7 %) and of low socio-economic status 132 (88.6%). One hundred
      and three (89.1 %) patients were in the age bracket 40-69 years with highest
      frequency in 40-49 years age group. The disease is associated with high parity
      with grandmultiparous patients constituting 119 (79.9 %) of the cases. Irregular
      vaginal bleeding 109 (73.2 %), vaginal discharge 58 (38.9%) and postcoital
      bleeding 31(20.5%) were the common symptoms. Nineteen (12.8%) patients reported
      at the hospital within one month of onset of symptoms. About three quarter ofthe
      patients had advanced disease and stage III disease was the most common stage 75
      (50.4 %). CONCLUSION: This study has shown a high incidence of carcinoma ofcervix
      at the University of Ilorin Teaching Hospital.

PMID- 15730092
TI  - Histomorphometric studies on the effect of cyanide consumption of the developing
      cerebellum of wistar rat (Rattus Novergicus).
AB  - OBJECTIVE: To investigate the microscopic effect of maternal cyanide consumption
      on the developing cerebellum of Wistar rats. MATERIALS AND METHODS: Twenty
      pregnant female rats weighing between 160 g and 180 g were used in this study.
      The rats were separated into two groups comprising ten control and ten
      experimental animals. The control animals were fed a standard diet of mice cubes,
      while the experimental animals were fed 500 ppm potassium cyanide, mixed with the
      standard diet. The diets were fed to the animals and their litters in separate
      cages and water provided ad libitum during pre and postnatal life. After birth,
      the offspring (five per group) of days 1,9,14,21,28 and 50 were weighed and
      killed by cervical dislocation. The cerebellar tissues were processed and
      microscopic parameters studied. RESULTS: A thicker external granular layer (EGL)
      was seen in the control group on day 1(39+/-9.2microm) compared with the
      experimental group (29+/-5.8microm) and on day 9(83+/-7.1microm) compared with
      the experimental group (78+/-13microm). However, these were not significantly
      different statistically. A thicker and persistent EGL was observed in the
      experimental group on days 14 and 21. A significant (P<0.05) reduction in the
      thickness of molecular layer (ML) was observed on days 28 and 50 in the
      experimental group. The density and size of the Purkinje cells were the same in
      both the control and experimental groups (P>0.05). CONCLUSION: Maternal
      consumption of 500 ppm cyanide in rats does not significantly affect light
      microscopic prenatal cerebellar development, but causes mild changes in the post
      natal life. Maternal cyanide consumption causes delayed maturation of the
      cerebellum, as evidenced by the thicker EGL, and reduction in the ML in the
      experimental group which become noticeable only at about 28th day of postnatal
      life.

PMID- 15730093
TI  - Vaginal birth after previous cesarean delivery: what are the most common signs of
      uterine rupture?

PMID- 15730094
TI  - Intestinal obstruction from a forgotten artery forceps: a case report.
AB  - A 43-year-old multiparous patient p2+0 all alive who had abdominal hysterectomy
      secondary to ruptured uterus 2 1/2 years prior to presentation, was seen with
      acute (surgical) abdomen. An artery forceps was seen on plain abdominal X-ray and
      subsequent laparotomy revealed gangrenous ileum. The entire length of the ileum
      was involved, including the ileocecal valve and part of the cecum. The patient
      had limited right hemicolectomy and anastomosis of the distal part of the jejunum
      with the proximal section of the transverse colon. The post-operative period was
      uneventful and she was discharged to outpatient clinic 2 weeks post operatively.

PMID- 15730095
TI  - Portal vein thrombosis complicating appendicitis.
AB  - Appendicitis is still the most common acute surgical abdomen all over the world
      and its complications may be grave. We report an adult case of acute appendicitis
      complicated by Portal Vein Thrombosis (PVT) and ascending portomesenteric
      phlebitis treated successfully with antibiotics and anticoagulation with no
      residual morbidity. Review of published works on the subject matter is also
      presented.

PMID- 15730096
TI  - Video-assisted thoracic surgery for spontaneous pneumothorax: outcome of 189
      cases.
AB  - The crucial role of video-assisted thoracic surgery (VATS) in the treatment of
      spontaneous pneumothorax is well acknowledged today. Experiences of such patients
      undergoing VATS were reported to evaluate the feasibility of such surgical
      approach. From January 1, 1996 to January 1, 2002, 189 patients (18.3%) underwent
      VATS treatment for first onset or recurrent primary pneumothorax (n = 134),
      secondary pneumothorax (n = 49), and re-do VATS (n = 6) pneumothorax of 1034 VATS
      procedures performed by one surgeon. The surgical approaches for these patients
      were through scope and working ports, and in six (3.2%) of them, the procedures
      were converted to open thoracotomy because of pleural adhesion or other causes.
      Bullae over apices or other sites of lung were identified in 164 (86.8%)
      patients. Mechanical pleurodesis with gauze abrasion or electrocoagulation was
      performed on all patients, and chemical pleurodesis with minocycline intrapleural
      injection or talc powder poudrage was performed on 144 (76.2%) of them. The
      bullae was excised with endo-GIA (n = 122), endo-loop (n = 23), electroablation
      (n = 9), and suturing through open or endoscopic port (n = 10). The operation
      time ranged from 23 to 355 minutes (42.4 +/- 12.6 minutes). The mean
      postoperative chest tube duration and hospital stay were 2.4 +/- 1.3 (range, 1
      26) and 4.3 +/- 1.2 (range, 1-35) days. Complication occurred in 15 cases (7.9%),
      including 9 patients with persistent air-leakage (> 7 days), 3 patients with
      bleeding, 6 patients with pneumonia or ventilator dependence, and 3 patients with
      wound infection. Recurrence occurred in six (3.2%) patients. Two patients (1.1%)
      died of complications related to underlying disease (severe emphysema)
      postoperatively. VATS treatment is a good choice for the treatment of recurrent
      primary spontaneous pneumothorax. It can also be used for patients with first
      onset spontaneous or traumatic pneumothorax with persistent air leakage or
      secondary pneumothorax. We preferred bullectomy with endo-GIA because it was
      safer, and the specimen could possibly reveal the underlying disease.

PMID- 15730097
TI  - Effect of Surgecel coverage with topical electrocauterization for preventing and
      sealing pulmonary air leakage.
AB  - Pleural tears usually occur after pneumolysis for dense adhesion or after cone
      biopsy of lung parenchyma. Repair of the tears is sometimes very difficult.
      Herein we compared different methods on a pig lung air leak model. Twenty pigs
      with pleural tears by surgical manipulation through sternotomy were not treated
      (n = 5) or treated by simple electroablation (n = 5), pleural coverage (n = 5),
      or Surgecel coverage with surface electroablation (n = 5). We evaluated their
      immediate and delayed treatment effect by measuring the critical leak pressure,
      degree of air leakage, and air leakage period and histological examination. It
      was found that Surgecel coverage with surface electrocauterization had similar
      early and delayed effects in sealing air leakage to pleural coverage and was much
      better than the other two groups (P < 0.05). We conclude that coverage with
      Surgicel with local electroablation can significantly decrease immediate and late
      air leakage from pleural tears.

PMID- 15730098
TI  - Successful late restoration of traumatic distal bronchial separation.
AB  - Traumatic distal bronchial interruption is unusual. A 42-year-old male with
      history of blunt injury to his chest and abdomen 20 years previously presented
      with recurrent pneumonia of the right lung. Patient's middle and lower lobes were
      partially atelectatic and the right intermediate bronchus was found completely
      dehisced at the time of surgical exploration. A direct re-implantation of
      intermediate bronchus was successfully performed. At late follow-up the
      anastomosis had healed well without any stricture and patient remains without
      symptoms.

PMID- 15730099
TI  - Treatment of palmar hyperhidrosis using needlescopic T2 sympathetic block by
      clipping: analysis of 102 cases.
AB  - Endoscopic thoracic sympathicotomy, or sympathectomy by a 2-mm scope, is an
      effective method for treating palmar hyperhidrosis. However, postoperative
      compensatory sweating may be troublesome in some patients. We report needlescopic
      T2 sympathetic block by clipping, which may provide reverse operation for
      patients encountering compensatory sweating. Between January 1998 and January
      2002, a total of 102 patients with palmar hyperhidrosis underwent video-assisted
      thoracoscopic sympathetic blocking of the T2 ganglion. There were 47 males and 55
      females (mean age, 24.1 years; range, 9-50 years). All patients were placed in a
      semi-sitting position under single-lumen intubated anesthesia. We performed T2
      sympathetic block by clipping at the second and third intercostal spaces using a
      2-mm, 0 degrees thoracoscope. Among these 102 patients, all bilateral T2
      sympathetic blockings were achieved. The operation was usually accomplished
      within 30 minutes (range, 16-40 minutes). All patients were discharged within 4
      hours after the operation. There were no surgical complications or surgical
      mortality cases. The mean postoperative follow-up period was 37.1 months (range,
      16-64 months). Improvement of palmar hyperhidrosis can be obtained in all
      patients. Eighty-six patients (84%) have developed compensatory sweating of the
      trunk and lower limbs. Two patients had a reverse operation and had improvement
      of compensatory sweating at 2 and 13 days after removal of endo clips.
      Needlescopic T2 sympathetic block by clipping is a safe and effective method for
      treating palmar hyperhidrosis; compensatory sweating may be improved after
      reverse operation removal of endo clip.

PMID- 15730100
TI  - Protection of trocar sites from gallbladder cancer implantation in a murine model
      by physically covering the sites.
AB  - Laparoscopic surgery for malignant diseases is associated with a risk for port
      site recurrence (PSR), and this problem remains to be resolved. This study was
      performed to evaluate the role that Seprafilm and Interseed (TC7) play in the
      prevention of PSR, using a nude mouse model of PSR. Nude mice with 2-mm port
      sites were created. The resultant peritoneal defects were covered with either
      Seprafilm or Interseed (TC7). The protective effect of Seprafilm and Interseed
      (TC7) on GB-dl (a human gallbladder cancer cell line) implantation at port sites
      was assessed after 7 days. In addition, the effects of Seprafilm and Interseed
      (TC7) on wound healing at the port sites were also observed. The Seprafilm and
      Interseed (TC7) groups showed a significantly lower incidence of PSR than the
      control group. Both Seprafilm and Interseed (TC7) changed into a gel form and
      covered the ruptured muscle layer and injured peritoneum for 3-5 days. When the
      peritoneal defect, produced by trocar insertion, was physically covered with
      either Seprafilm or Interseed (TC7), the incidence of PSR was observed to
      significantly decrease. These materials seem to be promising modalities for the
      prevention of PSR.

PMID- 15730101
TI  - Visual loss after shoulder surgery under general anesthesia diagnosed as caused
      by ocular compression with electroretinography testing: case report and review of
      the literature.
AB  - Ophthalmic complications after nonocular surgery are well documented in the
      ophthalmic, surgical, and anesthesia literature. A case of unilateral visual loss
      after shoulder surgery under general anesthesia is presented in which
      electroretinography (ERG) confirms ocular compression as the etiology of the
      visual loss. Compression is a preventable risk factor for perioperative visual
      loss, and its diagnosis has serious medico-legal implications. The importance of
      performing ERG testing in all unexplained cases of visual loss after nonocular
      surgical procedures is supported by this case to rule out ocular compression
      perioperatively. The abnormal decreased scotopic ERG B-wave amplitude in the
      affected eye compared with the normal eye confirms ocular compression, which can
      be prevented by proper positioning of the head and adequate headrest during
      general anesthesia.

PMID- 15730102
TI  - Spontaneous bilobar subcapsular hematoma of the liver while undergoing
      anticoagulation therapy: our experience and review of the literature.
AB  - We report on a case of bilateral subcapsular hematoma of the liver, occurring
      during treatment with warfarin. A 64-year-old woman was put on long-term warfarin
      therapy. After a bout of severe right hypochondriac pain, computed tomography
      (CT) scan showed subcapsular hematoma of the liver. Subsequent CT scan,
      conservative policy only, showed regression of the hematoma. The patient was
      discharged from the hospital on the 23rd day. We conclude that a nonruptured
      spontaneous liver hematoma should not be surgically removed. A conservative
      management with close observation is the mainstay therapy. A switch from warfarin
      therapy to another anticoagulation therapy is strongly suggested.

PMID- 15730103
TI  - Recording of surgery with two crane-type tripods and video cameras.
AB  - At medical meetings, a video-recorded surgical procedure can be more persuasive
      than an oral or poster presentation. Because operating rooms generally have
      limited space, video setups must be efficient and effective. Patients undergoing
      hepatectomy and rectal resection were recorded using two sectional crane-type
      tripods and video cameras placed in different positions. Both small crane-type
      tripods and video cameras could record surgical procedures from different angles
      and were easily controlled. Surgical procedures by the surgeon and first
      assistant were recorded independently. Videotaping surgical procedures with two
      video cameras can make presentations at medical meetings more effective.

PMID- 15730104
TI  - Pancreaticojejunostomy versus alternative treatment of the pancreatic stump after
      pancreaticoduodenectomy: a comparative analysis of early postoperative outcome.
AB  - The operative management of the pancreatic stump after pancreaticoduodenectomy
      has been shown to be an important factor influencing the postoperative
      development of pancreatic fistula. Thus far, there is no ideal technique for
      reconstruction, and end-to-end pancreaticojejunostomy (PJS) represents the
      preferable method. Comparative analysis of early postoperative outcome was done
      between two groups of patients who underwent either end-to-end PJS or pancreatic
      remnant ligation (PRL) after pancreaticoduodenectomy. Between January 1997 and
      December 2001, 39 consecutive patients underwent pancreaticoduodenectomy at the
      1st Department of Surgery, University of Athens Medical School. All operations
      were performed or supervised by two senior surgeons, and all patients underwent a
      Whipple's procedure. After pancreaticoduodenectomy, 23 patients underwent end-to
      end PJS (PJS group), whereas the remaining 16 patients underwent PRL without
      pancreatic reconstruction (PRL group). We compared the two groups in terms of
      patients' characteristics, clinical presentation, serum laboratory values on
      admission, operative details, and postoperative course. The morbidity and
      mortality rates were 15.4% and 5.1%, respectively, for the whole series. In the
      PJS group, the morbidity rate was 8.7%, the pancreatic fistula formation rate was
      4.3%, and the mortality rate was 4.3%. In the PRL group, the morbidity rate was
      25%, the pancreatic fistula formation rate was 12.5%, and the mortality rate was
      6.25%. These differences were not statistically significant. There were two
      deaths in the whole series (one in each group); however, none of the deaths were
      related to pancreatic fistula formation. Hospital stay was similar in both
      groups. Both PJS and PRL are valid surgical options that correlate with
      acceptable postoperative incidence of pancreatic fistula formation, morbidity,
      and mortality rates. Although PRL avoids the construction of the most risky
      anastomosis, the results of this study show that early postoperative results
      after PRL are not superior to PJS; therefore, the method should not be considered
      as the treatment of choice for the pancreatic stump after a Whipple's procedure.
      Meticulous surgical technique, surgical experience, and close postoperative care
      are essential for a successful outcome after this major abdominal operation.

PMID- 15730105
TI  - Anatomical deformities after laparoscopic antireflux surgery.
AB  - Laparoscopic Nissen, Nissen-Rossetti, cardial calibration with gastropexy, and
      other modifications are the procedures commonly used for surgical treatment of
      gastroesophageal reflux disease. Postoperative failures have been reported
      ranging from 10% to 15% associated with postoperative symptoms or recurrent
      gastroesophageal reflux. In this paper, we present 38 patients submitted to
      different procedures in which different "abnormal" deformities were found during
      the postoperative radiological evaluation with barium swallow. The symptoms
      associated with these deformities were pain (62%), dysphagia (43%), early satiety
      (37%), postprandial discomfort (35%), and recurrent postoperative reflux (30%).
      Dysphagia and pain were frequently observed after the Nissen-Rossetti technique,
      in which a bilobed stomach and stricture (46%) were confirmed. Hiatal hernia was
      observed in two patients, and slipped Nissen in one patient associated to pain
      and early satiety. Patients were submitted to conservative treatment (endoscopic
      dilatation, proton pump inhibitors, and prokinetics), but 10 patients were
      submitted to redo surgery. There were no complications, and good results were
      obtained after redo operations.

PMID- 15730106
TI  - Diaphyseal femoral fractures in children: should we change the present mode of
      treatment?
AB  - Three hundred thirty-nine diaphyseal fractures of the femur in 327 children were
      studied retrospectively. There were 196 boys and 131 girls, with a mean age of
      5.59 years (range, 1 day-14 years). The majority of the children were < 6 years
      of age. In 67.8% of the children, the fracture was caused by a road traffic
      accident. Seventy-seven of the children had associated injuries. The minimum
      hospital stay was 15 days, and the maximum was 42 days (mean, 32.6 days). The
      most common site of fracture was at the middle third (N = 206), and 133 were the
      transverse type. The mode of treatment was balance skin traction in 146, skeletal
      traction in 72, hip spica in 22, internal fixation in 16, and external fixators
      in 5. The average follow up was 7.8 years. Complications were few. Our experience
      indicates that with a conservative mode of treatment, there is no risk of
      overgrowth, and a rotational malalignment of up to 20 degrees corrects during
      growth. We believe that diaphyseal fractures of the femur in children can be
      safely managed nonoperatively and economically, contrary to the present advocacy
      of operative treatment. The operative mode of treatment should be used in
      selected cases.

PMID- 15730107
TI  - Systems Evaluation and pharmacy redesign needed in addressing medication errors.

PMID- 15730108
TI  - Hair follicle testing another option for controlling drug use in sports.

PMID- 15730109
TI  - Making all clinical trials available for review: any impact on clinical
      decisions?

PMID- 15730110
TI  - Several clinical-registry issues should concern practicing pharmacists.

PMID- 15730111
TI  - Clinical trial registry will positively influence pharmacy's future.

PMID- 15730112
TI  - Managing risk.

PMID- 15730113
TI  - Community pharmacy Target Intervention Program to improve aspirin use in persons
      with diabetes.
AB  - OBJECTIVE: To identify the rate of aspirin or antiplatelet/anticoagulant use in
      persons with diabetes presenting to community pharmacies and determine whether a
      student pharmacist-driven Target Intervention Program (TIP) could increase the
      number of eligible persons with diabetes receiving aspirin therapy in accordance
      with American Diabetes Association (ADA) recommendations. DESIGN: Unblinded,
      single intervention. SETTING: Eight Community Pharmacy Advanced Practice
      Experience (CPAPE) sites in New York State. PARTICIPANTS: Persons having
      prescriptions filled for diabetes medications or supplies who were not receiving
      antiplatelet/anticoagulant medications. INTERVENTIONS: Assessment sheets were
      completed by student pharmacists for eligible patients to determine
      appropriateness for aspirin therapy. Recommendations for aspirin therapy were
      faxed to physicians when indicated, and physicians responded via fax for aspirin
      therapy implementation. The student pharmacists contacted patients, informed
      patients of physician decisions, and provided appropriate counseling. MAIN
      OUTCOME MEASURES: Number of persons with diabetes currently receiving aspirin or
      antiplatelet/anticoagulant medications and the number initiated on aspirin as a
      result of the TIP. RESULTS: A total of 436 persons with diabetes were identified.
      Of those contacted, 322 agreed to participate and 31 declined; 228 were taking
      aspirin or other antiplatelet/anticoagulant agents at baseline. Students
      completed assessment sheets, which were forwarded to physicians, for 79 subjects
      potentially eligible to receive aspirin therapy; 65 physician responses were
      received (82% response rate). Aspirin therapy was initiated in 53 patients (67%).
      CONCLUSION: The TIP enabled CPAPE students to increase aspirin use among eligible
      persons with diabetes in accordance with ADA guidelines.

PMID- 15730114
TI  - Pharmacists' and technicians' perceptions and attitudes toward dispensing
      buprenorphine/ naloxone to patients with opioid dependence.
AB  - OBJECTIVE: To assess the perceptions and attitudes of pharmacists and pharmacy
      technicians involved in an office-based opioid dependence treatment program using
      buprenorphine/naloxone. DESIGN: Cross-sectional attitudinal assessment. SETTING:
      Community, outpatient hospital, and clinic pharmacies. PARTICIPANTS: Pharmacists
      and technicians participating in a clinical trial of opioid dependence treatment
      using buprenorphine/naloxone. INTERVENTION: Written and telephone surveys
      followed by interviews with open-ended items. MAIN OUTCOME MEASURES: Attitudes
      and perceptions regarding opioid-dependent patients and use of
      buprenorphine/naloxone for treatment of opioid dependence. RESULTS: Pharmacies in
      seven states (New York, Virginia, Illinois, Florida, Texas, California, and
      Washington) participated in the clinical trial. A total of 40 pharmacists and
      pharmacy technicians responded to the initial written survey, representing 27 of
      the 32 pharmacies (84%). Follow-up interviews were obtained from one individual
      at 30 of those pharmacies (93.8%). Most pharmacy personnel (77.5%) involved with
      this study were not more concerned about theft or break-ins and would be willing
      to participate in opioid dependence treatment as the medication became available
      commercially (70%). The majority of respondents (85%) indicated that patients did
      not cause problems at their pharmacies. Compared with their experiences in
      administering other narcotic medications, most respondents did not express
      increased concern regarding prescription forgery (75%) or diversion (80%) of
      buprenorphine/naloxone. CONCLUSION: The majority of respondents expressed
      positive attitudes and perceptions regarding patients treated for opioid
      dependence with buprenorphine/naloxone.

PMID- 15730115
TI  - Impact on medication use and adherence of Australian pharmacists' diabetes care
      services.
AB  - OBJECTIVE: To assess the effect of a specialized service implemented in community
      pharmacies for patients with type 2 diabetes on medication use and medication
      related problems. DESIGN: Parallel group, multisite, control versus intervention,
      repeated measures design, with three different regions in New South Wales,
      Australia, used as intervention regions, then matched with control regions as
      much as possible. INTERVENTION: After initial training, pharmacists followed a
      clinical protocol for more than 9 months, with patient contact approximately
      monthly. Each patient received an adherence assessment at the beginning and end
      of the study, adherence support, and a medication review as part of the
      intervention. MAIN OUTCOME MEASURES: Risk of nonadherence using Brief Medication
      Questionnaire (BMQ) scores and changes to medication regimen. RESULTS: Compared
      with 82 control patients, 106 intervention patients with similar demographic and
      clinical characteristics had significantly improved self-reported nonadherence as
      reflected in total BMQ scores after 9 months. The mean (+/-SD) number of
      medications prescribed at follow-up in intervention participants decreased
      significantly, from 8.2+/-3.0 to 7.7+/-2.7. No reduction was observed among the
      control patients (7.6+/-2.4 and 7.3+/-2.4). The overall prevalence of changes to
      the regimen was also significantly higher in the intervention group (51%)
      compared with controls (40%). CONCLUSION: Community pharmacists trained in
      medication review and using protocols in collaboration with providers improved
      adherence in patients with type 2 diabetes, reduced problems patients had in
      accessing their medications, and recommended medication regimen changes that
      improved outcomes.

PMID- 15730116
TI  - Community pharmacists' actions when patients use complementary and alternative
      therapies with medications.
AB  - OBJECTIVE: To assess actions of community pharmacists in response to their
      patients' concurrent use of prescription medications and complementary and
      alternative medicine (CAM). DESIGN: Nonexperimental, cross-sectional mail survey.
      SETTING: Texas. PARTICIPANTS: 107 community pharmacists. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Pharmacists' self-reported rate of patient
      inquiry about CAM use and actions taken in response to CAM use. RESULTS: A
      majority (71.0%) of pharmacists had encountered patients who were using CAM,
      which was defined broadly in the survey to include herbal products, vitamins and
      minerals, homeopathic products, massage, meditation, and other types of CAM.
      Pharmacists documented CAM use by patients in 11.0% of cases and reported
      monitoring for drug-related problems in 38.4% of users. Among CAM users,
      pharmacists most often encouraged CAM use if medically appropriate. Pharmacists
      were not comfortable with responding to CAM inquiries but believed they needed
      adequate knowledge about CAM. In general, pharmacists rarely asked patients about
      their CAM use. Pharmacists' rate of inquiry about CAM use increased significantly
      when this information could be documented in patient profiles and when
      pharmacists had additional training in CAM. Also, in pharmacies that stocked
      herbal or homeopathic products, pharmacists were significantly more likely to
      encourage the use of CAM when medically appropriate and to recommend other CAM
      therapies appropriate for patients' conditions. When no references were available
      to research CAM, pharmacists tended to neither encourage nor discourage CAM use
      based on lack of scientific evidence of their effectiveness. CONCLUSION: Most
      community pharmacists had patients who used CAM, but they were not proactive in
      inquiring about or documenting this use. They most often encouraged CAM use if
      deemed medically appropriate. Pharmacists' actions differed on the basis of
      professional and practice setting characteristics. To ensure optimal drug therapy
      outcomes, pharmacists should be more proactive in identifying and documenting CAM
      use by patients.

PMID- 15730117
TI  - Pharmacy-related health disparities experienced by non-english-speaking patients:
      impact of pharmaceutical care.
AB  - OBJECTIVES: To identify the availability of foreign language services in
      pharmacies near a medical clinic serving a large immigrant population and
      determine whether the type of observed drug therapy problems differed between
      English- and non-English-speaking patients at this clinic. SETTING: A community
      health care center in a diverse neighborhood of Minneapolis, Minnesota.
      PARTICIPANTS: 40 pharmacies near the clinic and in the surrounding Minneapolis
      St. Paul area known to provide services to patients in languages in addition to
      English and 91 clinic patients, including 38 for whom English was not their
      primary language, seen for full pharmaceutical care assessments. INTERVENTIONS:
      Comprehensive drug therapy assessments were conducted for English- and non
      English-speaking patients (with assistance from interpreters) in a primary care
      setting secondary to physician referral. Patient-specific data and the results of
      the pharmacist's assessment were recorded in a patient management database. MAIN
      OUTCOME MEASURES: Language services provided by area pharmacies, frequency of
      drug therapy problems in English- and non-English-speaking patients, and the
      status of patient's medication conditions before and after provision of
      pharmaceutical care. RESULTS: Of the six primary languages other than English
      (Vietnamese, Hmong, Laotian, Somali, Spanish, and Cambodian) spoken by clinic
      patients, written or verbal information was available for five languages in one
      or more area pharmacies. The clinic pharmacist completed comprehensive
      assessments for 91 patients via 230 patient encounters, identifying 186 drug
      therapy problems. Problems related to adherence were significantly more prevalent
      in non-English-speaking patients compared with English-speaking patients (31%
      versus 12%). In all 91 patients, the percentage achieving desired drug therapy
      outcomes improved by 24% after a pharmacist joined the team of clinic providers.
      CONCLUSION: Despite the availability of clinic-based interpreters and foreign
      language services in pharmacies, adherence-related problems are significantly
      more common in non-English-speaking patients. Pharmacists committed to providing
      pharmaceutical care must consider the impact of language barriers when working to
      optimize drug therapy outcomes.

PMID- 15730118
TI  - Pharmacy executive leadership issues and associated skills, knowledge, and
      abilities.
AB  - OBJECTIVES: To identify challenges that current and future pharmacy executives
      are facing or will face in the future and to define what skills, knowledge, and
      abilities (SKAs) are required to successfully negotiate these challenges. DESIGN:
      Delphi method for executive decision making. SETTING: Civilian pharmacy
      profession. PARTICIPANTS: 110 pharmacists who graduated from the GlaxoSmithKline
      Executive Management Program for Pharmacy Leaders. INTERVENTIONS: Two iterations
      of the Delphi method for executive decision making separated by an expert panel
      content analysis. MAIN OUTCOME MEASURES: Round 1--participants were asked to
      identify five major issues they believed to be of greatest importance to pharmacy
      leaders in the next 5-10 years and name specific SKAs that might be needed by
      future leaders to successfully deal with those issues. An expert panel reviewed
      the issues, classified issues into specific domains, and titled each domain.
      Round 2-participants rated the SKAs on a 7-point scale according to their
      individual assessment of importance in each domain. RESULTS: For Delphi rounds 1
      and 2, response rates were 21.8% and 18.2%, respectively. More than 100 total
      issue statements were identified. The expert panel sorted the issues into five
      domains: management and development of the pharmacy workforce, pharmacy finance,
      total quality management of work-flow systems, influences on the practice of
      pharmacy, and professional pharmacy leadership. Five of the top 15 SKAs-and all
      four highest ranked items--came from the professional pharmacy leadership domain,
      including ability to see the big picture, ability to demonstrate the value of
      pharmacy services, ability to lead and manage in an ethical manner, and skills
      for influencing an organization's senior leadership. CONCLUSION: Through
      successful integration of communication skills, critical thinking, and problem
      solving techniques, future public-sector pharmacy executives will be better
      equipped to effectively position their organizations and the profession for the
      challenges that lie ahead.

PMID- 15730119
TI  - Recreational use and misuse of phosphodiesterase 5 inhibitors.
AB  - OBJECTIVE: To characterize the rationale for and extent of phosphodiesterase
      (PDE) 5 inhibitor use in recreational settings, describe risks from such misuse,
      and discuss postexposure clinical management strategies. DATA SOURCES: Published
      articles identified by searches through Medline, EMBASE, International
      Pharmaceutical Abstracts, and Toxline, from 1990 to March 2004, using the search
      terms sildenafil, tadalafil, vardenafil, phosphodiesterase inhibitor, abuse,
      overdose, adverse effects, recreational, and street drugs. Additional references
      identified within articles and information from the Internet were included. STUDY
      SELECTION: Clinical trials, epidemiologic reviews, case reports, and news
      releases concerning the misuse of sildenafil. DATA EXTRACTION: By the authors.
      DATA SYNTHESIS: PDE5 inhibitors, indicated for treatment of erectile dysfunction,
      can produce several adverse effects, including potentially fatal cardiovascular
      events. Reports of recreational use and misuse of sildenafil appear in the
      medical literature and the media. The potential for abuse also exists for the two
      more recently approved drugs in this class, vardenafil and tadalafil. Increasing
      access to these drugs via the Internet may facilitate such misuse. Use in social
      settings has gained popularity, both in young, healthy patients, as well as those
      with chronic medical conditions, including human immunodeficiency virus
      infections. In these settings, the PDE5 inhibitors are sometimes used
      concomitantly with "club drugs" such as ketamine and amyl nitrite, leading to
      potentially harmful or fatal drug interactions. CONCLUSION: Pharmacists should be
      cognizant of the potential for PDE5 inhibitors to be misused, particularly in
      patients who are at greater risk of cardiovascular complications, and should
      advise patients and other health care professionals accordingly.

PMID- 15730120
TI  - Implementation of a patient medication assistance program in a community pharmacy
      setting.
AB  - OBJECTIVE: To describe the establishment of a community pharmacy-based patient
      medication assistance program to improve access to medications by indigent
      patients, lessen the burden placed on physicians in obtaining such medications,
      reduce the amount of money spent on such medications by area charitable
      organizations, and improve therapeutic outcomes by improving patient adherence
      with therapy. SETTING: Supermarket-based pharmacy in Ashland, Ohio. PRACTICE
      DESCRIPTION: Community pharmacy. PRACTICE INNOVATION: A partnership was developed
      among Buehler's Pharmacy #3, United Way of Ashland County, and United Way
      Affiliates to establish a community pharmacy-based medication assistance program
      to help indigent patients obtain needed medications through manufacturer
      assistance programs and discount card programs. INTERVENTIONS: Following initial
      screening by a United Way affiliate agency, patients are seen by appointment by a
      Certified Pharmacy Technician at the pharmacy. An electronic application is
      completed, printed, and sent to the patient's physician for signatures and
      medication orders. The paperwork is returned to the pharmacy, where it is
      completed, signed by the patient, and filed. The patient pays the United Way
      agency $10 and the pharmacy $15 for these services. MAIN OUTCOME MEASURES: Number
      of prescriptions dispensed cumulatively from April 1, 2003, to July 31, 2003,
      within the program, patients' cumulative savings, and community response.
      RESULTS: Between April 1, 2003, and July 31, 2003, a total of 123 patients and 47
      physicians were served, and 512 medications valued at $112,139.00 were applied
      for and/or procured. The time lapse between filing of paperwork and receipt of
      medications varies from 1 to 6 weeks. While some manufacturers ship product to
      physicians or directly to patients, the process works better when the product is
      sent to the pharmacy, where it can be added to the patient's profile, screened
      for drug interactions and allergies, and dispensed with proper labels and
      counseling. CONCLUSION: Establishing a community pharmacy-based medication
      assistance program is an innovative spin on the traditional physician office,
      advocacy, or health-system setting and was found to be beneficial to the
      patients, physicians and other health care providers, and the community it
      served.

PMID- 15730121
TI  - Community pharmacists and Colleges of Pharmacy: the Ohio partnership.
AB  - OBJECTIVE: To develop pharmacist practice standards, pharmacy preceptor
      standards, and objectives for students completing advanced practice community
      pharmacy rotations. SETTING: Ohio. PRACTICE DESCRIPTION: Pharmacy schools and
      community pharmacies that serve as advanced practice rotation sites. PRACTICE
      INNOVATION: Developed standards for preceptors and objectives for student
      experiences. INTERVENTIONS: Focus groups that included both community pharmacists
      and pharmacy faculty collaborated on defining key standards for advanced
      community pharmacy rotations. MAIN OUTCOME MEASURE: Not applicable. RESULTS:
      Three main documents were produced in this initiative, and these are provided as
      appendices to this article. Professional and patient care guidelines for
      preceptors define minimum standards for these role models. Expectations of
      pharmacists as preceptors provide insights for managing this student-teacher
      relationship, which is fundamentally different from the more common employer
      employee and coworker relationships found in pharmacies of all types. Objectives
      for student experiences during advanced practice community pharmacy rotations
      present core expectations in clinical, dispensing, patient education, wellness,
      and drug information areas. CONCLUSION: Through this collaboration, Ohio colleges
      of pharmacy developed a partnership with practitioners in community settings that
      should enhance the Ohio experiential educational program for student pharmacists.
      Use of the established guidelines will help educators and practitioners achieve
      their shared vision for advanced practice community pharmacy rotations and
      promote high-quality patient care.

PMID- 15730122
TI  - Utility of electronic device for medication management in patients with
      hypertension: a pilot study.

PMID- 15730123
TI  - Stability of filtered technetium TC-99m sulfur colloid.

PMID- 15730124
TI  - Albert Ethelbert Ebert (1840--1906): Founder of American Pharmacy's oldest award.

PMID- 15730125
TI  - Keeping up with trends and developments in immunizations.

PMID- 15730126
TI  - New drugs: acamprosate calcium and solifenacin succinate.

PMID- 15730127
TI  - OTC product: Loratadine for urticaria.

PMID- 15730128
TI  - The attempt to understand puerperal fever in the eighteenth and early nineteenth
      centuries: the influence of inflammation theory.

PMID- 15730129
TI  - The effects of the 1918-1919 influenza pandemic on infant and child health in
      Derbyshire.

PMID- 15730130
TI  - War syndromes: the impact of culture on medically unexplained symptoms.

PMID- 15730131
TI  - Evidence-based medicine in the eighteenth century: the Ingen Housz-Jenner
      correspondence revisited.

PMID- 15730132
TI  - An inspector calls: perspectives on the history of occupational diseases and
      accident compensation in the United Kingdom.

PMID- 15730133
TI  - Correlation of different biochemical parameters in blood sera of healthy and sick
      cows.
AB  - Metabolic diseases of cows represent the leading internal pathology in Lithuania
      in terms of incidence and economic impact. This paper summarizes the mineral
      metabolic state of milk cows, and details the influence of feeding on serum
      levels of calcium, nonorganic phosphorus, magnesium, potassium, sodium, glucose,
      total protein, and urea quantity, and correlationd among them, in healthy dry or
      post-calving cows as well as in cows with osteomalacia and milk fever after
      calving. There was less pronounced hypocalcaemia and there were only minor
      changes in phosphorus, magnesium, potassium and sodium in the serum of healthy
      dry and post-calving cows that had silage and mineral-vitamin supplements,
      compared to cows that did not have supplements and silage. There was a fall in
      calcium and phosphorus (to 1.89 +/- 0.12 mmol/L and 0.71 +/- 0.06 mmol/L,
      respectively) in the blood of cows sick with milk fever after calving, while
      levels of magnesium and potassium were increased. The correlation between calcium
      and phosphorus was r = 0.6993, p < 0.001 in the serum of sick cows. There was a
      fall in calcium, phosphorus and magnesium (to 1.86 +/- 0.46 mmol/L, 0.75 +/- 0.37
      mmol/L, and 0.60 +/- 0.19 mmol/L, respectively) and an increase in sodium level
      (to 158.90 +/- 19.30 mmol/L) in the blood of cows with osteomalacia in comparison
      with healthy cows.

PMID- 15730134
TI  - Canine haematopoietic chimerism analyses by semiquantitative fluorescence
      detection of variable number of tandem repeat polymorphism.
AB  - Canine models are successfully applied to the study of haematopoietic stem cell
      transplantation (HSCT). Monitoring of haematopoietic donor/recipient chimerism is
      of major significance in detecting and quantifying engraftment or graft rejection
      of the donor-derived haematopoietic cells after transplantation. Radioactive
      analyses of polymorphic microsatellite markers are commonly used for chimerism
      analyses. We describe an improved, non-isotopic method that is based on the
      analysis of microsatellite markers in donor and recipient cells using capillary
      electrophoresis and fluorescence detection. Artificial mixtures of donor and
      recipient DNA that were generated from peripheral blood mononuclear cells from
      dog leukocyte antigen-identical siblings were used to analyse the sensitivity of
      the assay. DNA from dogs that had received HSCT were also analysed in order to
      demonstrate the feasibility of the method in vivo. For chimerism analyses, six
      different microsatellite loci were systematically amplified using fluorescent PCR
      primer. The fluorescent polymerase chain reaction products were separated by
      capillary electrophoresis using POP4 on a 310 ABI Prism Genetic Analyzer. After
      electrophoresis, fluorescence signals were automatically sized and quantified
      using GeneScan software. The method described provides an accurate assessment of
      haematopoietic chimerism in the canine model with significantly reduced hands-on
      time compared to conventional gel electrophoresis.

PMID- 15730135
TI  - Expression of mRNA encoding interleukin (IL)-10, IL-12p35 and IL-12p40 in lungs
      from pigs experimentally infected with Actinobacillus pleuropneumoniae.
AB  - The expression of mRNA encoding interleukin (IL)-10, IL-12p35 and IL-12p40 was
      studied, by reverse transcription-polymerase chain reaction and by in situ
      hybridization with a non-radioactive digoxigenin-labelled cDNA probe, in formalin
      fixed, paraffin-wax-embedded lung tissue from pigs experimentally infected with
      Actinobacillus pleuropneumoniae. Forty-eight 7-week-old colostrum-deprived pigs
      were randomly allocated to infected (n = 24) or control (n = 24) groups. Three
      pigs from each group were euthanized at 3, 6, 9, 12, 24, 36, 48 and 60 h post
      inoculation (hpi). IL-10 mRNA was detected in the lung at 3 hpi, numbers of cells
      positive for IL-10 increasing at 36 hpi. IL-12p35 mRNA was detected in the lung
      at 3 hpi, numbers of cells positive for IL-12p35 increasing at 36 and 48 hpi and
      rapidly decreasing thereafter whereas IL-12p40 mRNA was constitutively expressed
      at low levels during the experiment. Hybridization signals for IL-10, IL-12p35
      and IL-12p40 were always associated with inflammation, in particular with
      macrophages and neutrophils within alveolar spaces. Expression of these cytokines
      was minimal in non-lesional lung of A. pleuropneumoniae-infected pigs and in
      normal lung from control pigs. In situ hybridization of A. pleuropneumoniae and
      these cytokines in serial sections of lung tissues indicated close co
      localization of A. pleuropneumoniae and these cytokines in pleuropneumonia. The
      results suggest that the expression of IL-10 and IL-12 play a role in
      pathogenesis of A. pleuropneumoniae infection.

PMID- 15730137
TI  - Cutaneous melanocytoma in a llama (Lama glama).

PMID- 15730136
TI  - 27 kDa Fasciola gigantica glycoprotein for the diagnosis of prepatent fasciolosis
      in cattle.
AB  - An indirect enzyme-linked immunosorbent assay (ELISA) using 27 kDa glycoprotein
      of Fasciola gigantica has been evaluated for its potential use in the diagnosis
      of bovine fasciolosis. Following experimental infection of rabbits, F. gigantica
      infection-induced antibodies were isolated and later used as ligands in affinity
      chromatography for isolation of infection-induced antibody-specific proteins.
      Among the five infection-specific proteins isolated, a glycoprotein of 27 kDa was
      later isolated by second-step purification using concanavalin A matrix. In
      crossbred cattle receiving different doses of infection (100, 200 and 400
      metacercariae), the anti-27 kDa antibodies were detected as early as the 2nd week
      post infection. No direct correlation between initial dose, antibody response and
      fluke establishment was recorded. No cross-reaction was noted with the sera of
      goats experimentally infected with Paramphistomum epiclitum. ELISA with the 27
      kDa glycoprotein could be a feasible diagnostic tool for the early detection of
      bovine fasciolosis.

PMID- 15730138
TI  - Influence of fluid therapy on gentamicin pharmacokinetics in colic horses.
AB  - The aminoglycoside antibiotic gentamicin is commonly used in equine medicine for
      the prevention and treatment of Gram-negative and staphylococcal bacteria in
      surgically treated colic patients. The pharmacokinetics of gentamicin in these
      patients might be altered by the disease status, and/or under the influence of
      fluid therapy. The purpose of this study was to investigate the effect of
      intravenous fluid treatment on gentamicin kinetics in colic patients. Colic
      patients subjected to laparotomy were given fluid infusions according to clinical
      status. Following gentamicin administration, blood samples were taken for
      gentamicin analysis at different time points, and the main pharmacokinetic
      parameters including Vc, Vss, t(1/2) and MRT were calculated. Horses undergoing
      fluid therapy showed a significantly different t(1/2), clearance and MRT as
      compared to non-infused patients. However, taking into account the clinical
      status of the patients receiving fluid support, the data suggest that
      endotoxaemia, rather than fluid therapy, influence gentamicin pharmacokinetics
      following laparotomy.

PMID- 15730139
TI  - Effects of training on phagocytic and oxidative metabolism of peripheral
      neutrophils in horses exercised in the aerobic-anaerobic transition area.
AB  - Using simple techniques, the neutrophil function, in its phagocytosis and
      oxidative metabolism stages, was evaluated in horses. This was done before and
      after moderate exercise at the aerobic-anaerobic threshold (standardized heart
      rate 150 beats/min and lactate level of 3.07 +/- 0.21 mmol/L). The objective was
      to determine whether regular training and moderate exercise improved the
      neutrophil function. A group of 19 horses was used; 11 of these were untrained
      and the remainder trained for national jumping events. The exercise test
      consisted of a 5 min trot followed by a 3 min gallop on a long lunge. Blood
      samples were taken for analysis before, immediately after and 15 min after
      exercise. The results showed that (a) there is a difference in the
      internalization of particles (PI, PP and PE) by neutrophils from trained and
      untrained horses at a single time point during active recovery, and PP is higher
      in trained horses immediately after exercise; and (b) oxidative metabolism is
      significantly lower in untrained animals before and 1 min after exercise. The
      moderate exercise at the aerobic-anaerobic threshold did not have any influence
      on the peripheral blood neutrophil function of the phagocytosis and oxidative
      metabolism of particles.

PMID- 15730140
TI  - Quantitative and qualitative study of enzyme-linked immunosorbent assay to detect
      IgG against Japanese encephalitis virus in swine sera.
AB  - This study was designed to investigate the application of indirect enzyme-linked
      immunoassay (ELISA) in detecting IgG against Japanese encephalitis virus in swine
      sera and the qualitative nature of this test. The attenuated strain SA14-14-2 of
      Japanese encephalitis virus (JEV) was inoculated into 9-day-old chicken embryos
      and virus was harvested, purified and suspended in 0.9% saline as JEV antigen.
      The control antigen was prepared by the same method as for the antigen. In the
      ELISA, the optimal concentrations of antigen coated and dilution factor were
      selected using chi2 test. Ninety-two swine sera negative to haemagglutination
      inhibition (HI) were tested by this assay and the positive threshold was
      determined. The results of this study indicate that indirect ELISA has high
      specificity, sensitivity and reproducability. Simultaneous testing of 74 serum
      samples from nine pig farms was carried out to compare the existing HI test and
      the indirect ELISA. The coincidence rate of the two assays was 85.1% (63/74) and
      no significant difference was observed between them (p > 0.05). This ELISA test
      can detect 46 swine serum samples qualitatively and the titre of eight swine
      serum samples through endpoint dilution quantitatively within one 96-well plate.

PMID- 15730141
TI  - Haemagglutination inhibition antibodies, rectal temperature and total protein of
      chickens infected with a local Nigerian isolate of velogenic Newcastle disease
      virus.
AB  - Changes in values of haemagglutination inhibition (HI) antibody titre, rectal
      temperature (RT) and total protein (TP) were determined for Shaver Brown chickens
      infected with Newcastle disease virus (NDV) Kudu 113. The infected chickens came
      down with Newcastle disease by day 3 post infection (PI). The major clinical
      signs were depression, greenish diarrhoea, paralysis of legs and wings,
      opisthotonus and torticolis. Mortality and morbidity were 52% and 1000%,
      respectively. There were haemorrhagic lesions in the wall of the intestine,
      proventricular mucosa and caecal tonsils. There were necrosis and mononuclear
      cell infiltration of the liver, kidney and spleen. There was a significant
      increase in daily mean HI antibody titres from days 3 to 9 PI. Similarly,
      significant rise in daily mean RTs were noticed in the infected chickens from
      days 1 to 13 PI. On the other hand, there was a decrease in daily mean TP
      concentrations of infected chickens, beginning from day 3 PI, and the lowest
      concentration of 2.60 +/- 0.15 g/dl was obtained by days 7 and 11 PI. The values
      of HI, RT and TP for the control chickens were relatively constant during the
      experiment. The correlation coefficient (r) between HI and RT was positive and
      highly significant (r = 0.725, p<0.001), while the relationship between HI and TP
      was negative but highly significant (r = -0.712, p<0.001). It was concluded that
      NDV Kudu 113 induced increases in values of HI and RT, which occurred
      concurrently with a decrease in TP concentrations of infected chickens.

PMID- 15730143
TI  - [Schelling and experiential science].
AB  - Schelling's philosophy of nature is shown to be part of the scientific
      discussions of his day, not set apart from it. His terminology describing the
      potentialities and polarities of nature was formed during Schelling's
      collaboration with the physicist Johann Wilhelm Ritter. This scientist adopted
      the schema Schelling had developed for the categorization of natural phenomena to
      describe the peculiar facts that interested him in his area of research. Thus
      Ritter was able to develop a classification of the various phenomena of animal
      galvanism. Thus it can be shown that the idealistic "Naturphilosophie" was part
      of the scientific culture of about 1800. It is to be interpreted as philosophy of
      science and has to be evaluated not only in a philosophically systematic way but
      in particular in its influence on the way scientific categories were ordered at
      the time. Thereby it can be shown that the idealistic vocabulary had close
      correspondence to French morphology and English Natural Theology.

PMID- 15730144
TI  - [Old English plant names from the linguistic and lexicographic viewpoint].
AB  - Roughly 1350 Old English plant names have come down to us; this is a relatively
      large number considering that the attested Old English vocabulary comprises ca.
      24 000 words. The plant names are not only interesting for botanists, historians
      of medicine and many others, but also for philologists and linguists; among other
      aspects they can investigate their etymology, their morphology (including word
      formation) and their meaning and motivation. Practically all Old English texts
      where plant names occur have been edited (including glosses and glossaries), the
      names have been listed in the Old English dictionaries, and some specific studies
      have been devoted to them. Nevertheless no comprehensive systematic analysis of
      their linguistic structure has been made. Ulrike Krischke is preparing such an
      analysis. A proper dictionary of the Old English plant names is also a
      desideratum, especially since the Old English dictionaries available and in
      progress normally do not deal with morphological and semantic aspects, and many
      do not provide etymological information. A plant-name dictionary concentrating on
      this information is being prepared by Hans Sauer and Ulrike Krischke. In our
      article here, we sketch the state of the art (ch. 1), we deal with some problems
      of the analysis of Old English plant names (ch. 2), e.g. the delimitation of the
      word-field plant names, the identification of the plants, errors and problematic
      spellings in the manuscripts. In ch. 3 we sketch the etymological structure
      according to chronological layers (Indo-European, Germanic, West-Germanic, Old
      English) as well as according to the distinction between native words and loan
      words; in the latter category, we also mention loan-formations based on Latin
      models. In ch. 4 we survey the morphological aspects (simplex vs. complex words);
      among the complex nouns, compounds are by far the largest group (and among those,
      the noun + noun compounds), but there are also a few suffix formations. We also
      briefly present some morphological peculiarities, e.g. formations with blocked
      (unique) morphemes, the question of homonyms, cases of obscuration and of popular
      etymology. In ch. 5 we outline semantic structures, and in ch. 6, we introduce
      the structure of the proposed dictionary of the Old English plant names, also
      providing several specimen entries.

PMID- 15730145
TI  - [Good work: "attending to responsibilities" and "greater expections": assessment
      pattern of attendant behavior and introduction of non-restraint].
AB  - According to influential alienists nurses and attendants played a decisive role
      in the non restraint system. When Wilhelm Griesinger tried to implement this mode
      of treatment at the Berlin Charite he harshly criticized the often uneducated
      attendants. In this article judgments of conduct and behaviour of nurses and
      attendants are interpreted. These judgments displayed different cultural patterns
      on the part of the superiors of the attendants. Whereas the ,,Hausvater" Kruger
      saw ,,diligence" as the core attribute of ,,good labour", Carl Westphal, then
      functioning head of the psychiatric ward before Griesingers appointment, rather
      emphasized the fulfillment of official regulations. Griesingers criteria however
      were different from that. Attendants not only had to be diligent, non restraint
      posed ,,higher requirements": Nurses and attendants should be more educated and
      humane. In contradiction to Kruger and Westphal he not only judged the behaviour
      but also the mentality of the personal.

PMID- 15730146
TI  - [Wurzburg medicine in the middle ages. Remarks on a missed chance].
AB  - The University of Wurzburg was Germany's sixth academic institution, and was
      established in 1402, after the universities of Prague, Vienna, Heidelberg,
      Cologne and Erfurt. In 2002 the University of Wurzburg celebrated its 600th
      anniversary, and a great deal of information was made public at that time. Of
      particular interest are the articles that were published under the auspices of
      the University, although, unfortunately, these fail to depict the role of
      medicine in Wurzburg during the 13th and 14th centuries. There is evidence that,
      in those days, not only was academic life of great importance, but that lessons
      in medical science were also given at a high academic level. Our studies tell
      about the unfortunate circumstances that resulted in the failure to provide an
      accurate description of this teaching.

PMID- 15730147
TI  - [Enormous productive capacities of children and adolescents].

PMID- 15730149
TI  - [Drawings and art work in systemic family therapy].
AB  - As in most other forms of psychotherapy, creative media are an essential
      ingredient of systemic therapy with children, adolescents and their families.
      Therapists cannot rely solely on verbal interventions but rather have to utilize
      the natural tendency of children to express themselves through drawings and art.
      The therapeutic functions of creative expression in systemic therapy are being
      discussed. An overview of a variety of techniques with case examples is given
      that illustrates the many forms and uses of creative techniques in systemic
      family therapy.

PMID- 15730148
TI  - [How children show positive and negative relationships on their drawings].
AB  - This study analyses, whether pictures of children showing a positive relationship
      are significantly different from those showing a negative one with respect to
      several criteria. The study involved a random selection of 45 children aged 4;6
      to 11;6 years. The children painted a picture with themselves and a person they
      liked and a picture of themselves with someone they disliked. For the most part,
      the children drew pictures of themselves with peers both with respect to positive
      as well as negative images. In an interview afterwards, the children specified
      the criteria in their drawings by which the quality of the particular
      relationship can be identified. Positive and negative relationship paintings
      differ in the character of activity described. The sun as an element in
      children's paintings is painted not more frequent on positive compared to
      negative pictures. The colour black is used more often in the drawings signifying
      negative relationships. While girls used more colour in negative relationship
      drawings, boys used more colour in the positive ones. There was no significant
      difference in the use of favourite colours and decorative elements between the
      two groups. Only in negative relationship drawings people were looking away from
      each other. Smiling individuals were more common in the positive relationship
      pictures and in pictures painted by the 6 to 8 year olds. A greater distance
      between the individuals emerged on negative relationship drawings of the girls.

PMID- 15730150
TI  - [From Rambo-Jesus to well integrated masculinity].
AB  - The contribution deals with drawings of an eleven year old boy. He is in the
      transitional phase from preadolescence to adolescence. The atmosphere at home is
      very aggressive due to the prolonged divorce of his parents, which has been going
      on for three years. Because of this the typical development in this phase of
      growing up is made much more difficult for him. The youngster finds himself in an
      intensive loyality conflict with his parents. In his opinion any kind of
      aggression is negatively connoted. Therefore he cannot use his aggressions in a
      positive way neither to promote his self-development nor to become independent.
      His ability to symbolize was initially inhibited and could be released in the act
      of drawing during therapy. The boy's way from denial to showing his inner
      conflicts is described in the contribution.

PMID- 15730151
TI  - [Children's drawings: a case study of the psychotherapeutic treatment of a seven
      year old boy].
AB  - The paper explores the meaning of childrens' pictures as a symbol for growing
      autonomy. The psychotherapy of a 7-years old turkish boy, who came to treatment
      with a destroyed identity, will be described. The parents failed to support the
      boy's development by adequate mothering. The aggressive symptomatic as it emerged
      at the beginning of the psychotherapy is shown in a shipwreck. During therapy he
      succeeds to develop age-appropriate autonomy that is shown in a series of
      drawings.

PMID- 15730152
TI  - Emerging technologies: The PARIS project.

PMID- 15730153
TI  - Emerging technologies: All-in-one security.

PMID- 15730154
TI  - Emerging technologies: Genomic messaging.

PMID- 15730155
TI  - Emerging technologies: The nouse.

PMID- 15730156
TI  - Emerging technologies: Ultrasensitive diagnostics.

PMID- 15730157
TI  - Emerging technologies: Cell microprocessors.

PMID- 15730158
TI  - Emerging technologies: Smart sensors.

PMID- 15730159
TI  - Emerging technologies: Wearable computers.

PMID- 15730160
TI  - Emerging technologies: WiWAN.

PMID- 15730161
TI  - Emerging technologies: Home monitoring devices.

PMID- 15730162
TI  - A clearer outlook. Analysis of U.S. health insurers indicates long-term
      stability.

PMID- 15730163
TI  - Exploit your assets. Analyzing and managing the IT you have helps you buy what
      you need.

PMID- 15730164
TI  - Cardiology connections. Some industry experts predict integration within the
      decade.

PMID- 15730165
TI  - Retrospective histopathologic reevaluation of 18 cases of plasma cell vulvitis.
AB  - OBJECTIVE: To determine some common histologic features in a series of plasma
      cell vulvitis (PCV) cases. STUDY DESIGN: In a retrospective study, 18 histologic
      sections, previously obtained by vulvar biopsy in women diagnosed as having PCV,
      were critically reevaluated by the same pathologist. RESULTS: We observed that
      plasma cells in the dermal infiltrate were frequently present in a high
      percentage. Hemosiderin deposition and epithelial atrophy were 2 other histologic
      parameters useful for the diagnosis of PCV. Lozenge-shaped keratinocytes were
      rarely observed. CONCLUSION: In our series of PCV the percentage of plasma cells
      seemed to be the most important parameter when making the diagnosis. In
      particular, when this percentage was > or = 50% it was a sufficient histologic
      parameter for a diagnosis of PCV. When the percentage was 25-50%, hemosiderin
      deposition and epithelial atrophy were additional histologic features helpful in
      diagnosing PCV. Under 25% plasma cells was nonspecific and related to the mucosal
      site of involvement.

PMID- 15730166
TI  - Barriers to health care and protocol-based treatment of ectopic pregnancy.
AB  - OBJECTIVE: To evaluate whether treatment provided for ectopic pregnancies was
      different for patients with identified barriers to health care, including
      ethnicity, lack of insurance, distance from the treating facility that provides
      services and undocumented residency, at an institution that utilizes a protocol
      based algorithm for treatment of ectopic pregnancies. STUDY DESIGN: Charts of 401
      patients who were diagnosed with ectopic pregnancy from January 1, 1993, through
      December 31, 1998, were reviewed to compare the use of medical treatment using
      methotrexate versus surgical treatment. Data were analyzed with respect to
      patient ethnicity, socioeconomic status (including insurance status and
      possession of a social security card [a proxy for legal residency status]),
      residence inside or outside the county of the treating facility, patient
      presentation and treatment outcomes. RESULTS: There was no difference in
      treatment modality or success of primary treatment for ectopic pregnancies
      between groups regardless of ethnicity, health care insurance, residence outside
      the county the treating facility was located in or possession of a social
      security number. CONCLUSION: The treatment of ectopic pregnancies at the
      University of New Mexico Health Sciences Center is consistent across ethnic and
      socioeconomic populations. A well-designed treatment protocol may help provide
      evidenced-based, consistent treatment for patients requiring care who also have
      identified barriers to medical and surgical treatment.

PMID- 15730167
TI  - CIN in pregnancy: antepartum and postpartum cytology and histology.
AB  - OBJECTIVE: To determine the rates of antepartum and postpartum cervical
      intraepithelial neoplasia (CIN) 2 or worse in pregnant women with abnormal
      cervical cytology. STUDY DESIGN: A prospective, cohort study of 283 pregnant
      women referred for colposcopy between 1992 and 1999 for the evaluation of
      abnormal Pap smears. In this analysis, the population was stratified by severity
      of referral cytology (atypical squamous cells of undetermined significance
      [ASCUS] or low grade squamous intraepithelial lesion [LSIL] versus high grade
      squamous intraepithelial lesion [HSIL] and atypical glandular cells of
      undetermined significance [AGUS]). RESULTS: Sixty-seven women (24%) had ASCUS,
      147 (52%) LSIL, 67 (24%) HSIL and 2 (0.7%) AGUS. As compared to women with HSIL
      or AGUS, women with ASCUS or LSIL were less likely to undergo antepartum biopsy
      (relative risk [RR] .34, 95% CI .23-.51) and if biopsied, less likely to have CIN
      2 or worse (OR .49, 95% CI .24-.99). Women with antepartum ASCUS or LSIL were
      less likely to have postpartum HSIL (OR .29, 95% CI, .17-.52) and tended to have
      fewer histologically severe biopsies as compared to women with antepartum HSIL
      (OR .55, 95% CI .31-1.05). CONCLUSION: Among those biopsied, pregnant women with
      mildly abnormal cytology (ASCUS or LSIL), as compared to pregnant women with
      HSIL, were less likely to have either antepartum or postpartum CIN 2 or worse.

PMID- 15730168
TI  - A concise method of calculating fetal weight percentile.
AB  - OBJECTIVE: Assessment of fetal growth used in clinical decision making for
      managing pregnancies is based on percentiles relative to normal values for
      gestational age. Most clinicians utilize visual interpolation of look-up tables
      or graphs, which is neither accurate nor convenient. Calculation of growth
      percentile by numerical integration formulas requires digital computers with
      advanced computational capabilities and/or the storage of large data tables.
      STUDY DESIGN: Using established ultrasound measurement formulas and published
      fetal weight/gestational age tables, mean weights and standard deviations for
      gestational ages from 10 to 44 weeks were determined. From this Z-scores were
      calculated for the gestational ages. Z-scores plotted against 1st through 50th
      percentiles resulted in a curve. A polynomial equation was derived to fit the
      curve resulting in an expression for converting the Z-score to percentile:
      Percentile = 0.0994 * Z score2 - 0.44 * Z score + 0.5026. RESULTS: Comparing
      calculated values from this equation against standard percentiles from a Z-score
      to percentile table, all calculated values varied from the table value by < 1
      percentile for Z-scores ranging from 0 to 2.33. Values > 2.33 are assigned to the
      99th percentile. The equation performed to the goal of calculating percentile to
      an accuracy of < or = 1 percentile. CONCLUSION: A method whereby the estimated
      fetal weight can be used to calculate a percentile using two simple equations and
      only standard math functions allows implementation on a standard personal digital
      assistant device commonly available for clinical use. This implementation gives
      the needed accuracy, ease of interpretation, and portability, making it a useful
      tool in clinical practice.

PMID- 15730169
TI  - Association of spontaneous perineal stretching during delivery with perineal
      lacerations.
AB  - OBJECTIVE: To evaluate the effect of perineal stretching on perineal damage
      during vaginal delivery. STUDY DESIGN: Patients at term in active labor were
      included. Perineal length was measured during the active phase, second stage and
      24 hours postpartum. Perineal damage was assessed before repair and 24 hours
      postpartum. RESULTS: Three hundred women were included. Mean perineal length
      during the active phase was 4.02 +/- 1.07 cm, and mean stretching was 2.25 +/-
      1.2 cm. Of the parturients who had stretched the perineum > 150%, 40.7% required
      perineal repair as compared with 19.5% of parturients with less perineal
      stretching (p < 0.005). Significant risk factors included: age and parity,
      ethnicity, use of epidural, second-stage length, and perineal stretching.
      Stretching of > 150% remained significant in a multivariate mode (OR 2.11, p <
      0.01). CONCLUSION: Second-stage perineal stretching > 150% was predictive of
      perineal damage. In trying to avoid unnecessary episiotomies, this method may
      prove helpful.

PMID- 15730170
TI  - Gynecologic oncologists' perceptions of fellowship training.
AB  - OBJECTIVE: To determine fellowship satisfaction through a survey of practicing
      gynecologic oncologists. STUDY DESIGN: A survey was sent to all candidate members
      of the Society of Gynecologic Oncologists listed in the 2000 directory. Surveys
      were returned anonymously and confidentially. Questions focused on demographics,
      research, clinical opportunity and educational experience, satisfaction with
      fellowship training and career choice. Associations between variables were
      studied using chi2 and two-tailed t tests. RESULTS: Of the surveys sent, 47.1%
      (71/156) were returned. Average time out of fellowship was 3.6 years, 94.6% were
      currently performing research, and 47.3% did not publish their basic science
      research as a fellow, with 20.3% citing lack of mentorship as the main reason.
      Clinically, hands-on experience and faculty involvement were the top areas
      influencing surgical training during fellowship. Surgical, chemotherapy and
      radiation therapy training was adequate according to 90.5%, 94.6%, and 98.6%,
      respectively. Of those surveyed, 86.5% recommended a statistics course, and 81.5%
      recommended didactics specific to fellows; however, only 59.5% had received such
      teaching. Of the respondents, 44.6% and 40.8% had an opportunity to evaluate
      their fellowship and attending staff, respectively, as compared to 70.8%
      receiving routine performance evaluations (p = 0.001 and 0.0003, respectively);
      98.6% and 89.2% were satisfied and recommended their fellowships. The areas of
      greatest satisfaction were surgical training and clinical experience. The areas
      of least satisfaction were didactics, basic science and clinical research. In
      all, 95.9% were satisfied with their career choice. CONCLUSION: Areas in which
      fellowship satisfaction could improve are formal didactics and improved mentoring
      in research. Fellowship and faculty evaluations could provide a forum to continue
      to improve training programs. Respondents thought that they were sufficiently
      trained and were satisfied with their career choice.

PMID- 15730172
TI  - Transvaginal repair of the posthysterectomy vesicovaginal fistula using a
      peritoneal flap: the gold standard.
AB  - OBJECTIVE: To evaluate the transvaginal approach to management of vesicouterine
      fistulas. STUDY DESIGN: Over a 10-year period, 7 cases of simple posthysterectomy
      vesicovaginal fistulas were identified. The surgical technique involved resection
      of the fistulous tract completely, performance of layered closure and placement
      of a peritoneal flap between the bladder and vaginal suture lines. RESULTS: One
      fistula closed spontaneously, and the remaining 6 were repaired transvaginally.
      Primary repair was successful in all cases, with no complications. CONCLUSION:
      The transvaginal repair described is the preferred method of repair, associated
      with an extremely high success rate, low morbidity and cost savings. Its approach
      should be considered the gold standard.

PMID- 15730171
TI  - Dose effects of progesterone in add-back therapy during GnRHa treatment.
AB  - OBJECTIVE: To compare 1 mg norethisterone acetate with 5 mg norethindrone when
      used in conjunction with 2 mg estradiol given as add-back therapy during
      treatment with a gonadotropin-releasing hormone agonist (GnRHa). STUDY DESIGN: A
      prospective, double-blind, randomized study was conducted in a university-based
      teaching hospital. Forty-seven patients with pelvic endometriosis were recruited.
      Subcutaneous GnRHa was administered at 6-week intervals, and add-back therapy was
      commenced with the second dose of GnRHa. Group A patients received 2 mg estradiol
      and 1 mg norethisterone acetate, while group B patients received 2 mg estradiol
      and 5 mg norethindrone daily. Changes in bone mineral density, menopausal
      symptoms, lipid profile and occurrence of breakthrough bleeding were assessed
      before and after treatment. RESULTS: Patients in group A had no significant bone
      loss and satisfactory control of menopausal symptoms. The additional dose of
      progestogen in group B had a deleterious effect on the lipid profile and
      increased the frequency of breakthrough bleeding. CONCLUSION: In this study, the
      benefits of add-back therapy during GnRHa treatment were not enhanced, and a
      deleterious effect upon the lipid profile was seen when using a constant dosage
      of 2 mg estradiol and 5 mg norethindrone as compared to 1 mg norethisterone
      acetate.

PMID- 15730173
TI  - Office hysteroscopy: comparison of 2.7- and 4-mm hysteroscopes for acceptability,
      feasibility and diagnostic accuracy.
AB  - OBJECTIVE: To compare 2.7- and 4-mm rigid optics, with 3- and 5-mm outer sheaths,
      respectively, in office diagnostic hysteroscopy by evaluating pain, patient
      tolerability, optical view and diagnostic accuracy of the procedure. STUDY
      DESIGN: Three hundred seventy-one consecutive patients undergoing hysteroscopy
      were included in a prospective, randomized clinical trial, and the outcomes were
      analyzed. A saline solution was used as the distension medium. The t test for
      unpaired samples, chi2 tables of contingency and ANOVA 2 x 3 were used where
      appropriate. The study took place at Tor Vergata University Hospital of Rome,
      Rome, Italy. The 371 women were referred consecutively for suspected endometrial
      pathologies and were separated into 2 groups. Diagnostic accuracy of the
      hysteroscopic procedure, pain experienced by the 2 groups (as assessed by a
      visual analogue score) and patient acceptability were assessed with a
      questionnaire. RESULTS: Satisfactory hysteroscopy was achieved in 253 of 310
      patients with a 2.7-mm hysteroscope and in 47 of 61 patients with a 4-mm
      hysteroscope. This difference was not significant. Menopausal status was the most
      important factor influencing the practicability of the hysteroscopic procedure (p
      < 0.001). CONCLUSION: The narrower-diameter hysteroscopes tended to lower the
      incidence of pain associated with office hysteroscopy, but this was not
      significant. Parity did not show any influence on hysteroscopic practicability.
      Menopausal status was the most important factor influencing the feasibility of
      the hysteroscopic procedure.

PMID- 15730174
TI  - Childhood nocturnal enuresis in vulvar vestibulitis syndrome.
AB  - OBJECTIVE: To define correlations between vulvar vestibulitis syndrome (VVS) and
      childhood nocturnal enuresis and the effect of biofeedback therapy. STUDY DESIGN:
      Of 104 women diagnosed with VVS, 54 (30 with primary vulvar vestibulitis syndrome
      [PVVS] and 24 with secondary vulvar vestibulitis syndrome [SVVS], mean age 24.5
      years) chose Glazer biofeedback therapy. Information on lower urinary tract
      symptoms was recorded at the initial and final visits. RESULTS: Eight of the 30
      women with PVVS (26.6%) had a history of childhood enuresis as compared to none
      of the women with SVVS (p < 0.01). The 8 women developed lower urinary tract
      symptoms following biofeedback treatment. None of the women with SVVS had urinary
      symptoms before or following biofeedback therapy. The high, unstable baseline
      muscle tone revealed by the Glazer technique to be present in all VVS patients
      underwent substantial reduction and stabilization at the end of biofeedback
      therapy. CONCLUSION: Childhood nocturnal enuresis is apparently common among
      women with PVVS. New urinary symptoms may develop following biofeedback therapy
      for PVVS.

PMID- 15730175
TI  - Ultrasound and MRI appearance and evolution of hydranencephaly in utero: a case
      report.
AB  - BACKGROUND: Hydranencephaly is the total or near-total destruction of the
      cerebral cortex and basal ganglia. The thalami and lower brain centers are
      typically preserved. This condition is usually preceded by occlusion of the
      internal carotid arteries, resulting in massive brain infarction. CASE: An 18
      year-old woman, gravida 1, presented with a 1-day history of heavy vaginal
      bleeding at 23 weeks' gestation. Initial ultrasound revealed oligohydramnios and
      retroplacental lucency consistent with placental abruption. A follow-up level II
      ultrasound revealed abnormal intracerebral architecture. Subsequent ultrasounds
      and magnetic resonance imaging (MRI) revealed an evolving case of
      hydranencephaly. Postdelivery computed tomography verified the prenatal findings.
      CONCLUSION: Ultrasound and MRI are useful radiologic studies to confirm the
      diagnosis of hydranencephaly.

PMID- 15730176
TI  - Arteriovenous malformation in a bicornuate uterus leading to recurrent severe
      uterine bleeding: a case report.
AB  - BACKGROUND: Uterine arteriovenous malformations (AVMs) are rare entities that
      have been documented in a wide age range. Several treatment modalities have been
      highlighted in the literature. Uterine artery embolization appears to be
      effective therapy for select cases. Embolization provides an alternative to
      hysterectomy and the potential for future fertility. To our knowledge, only 1
      other case report describes an AVM existing within a bicornuate uterus. CASE: A
      31-year-old, married, Caucasian woman with a history of infertility presented
      with intermittent uterine hemorrhage resulting in symptomatic anemia. The patient
      was diagnosed with a uterine AVM existing within the left horn of a bicornuate
      uterus. The patient underwent uterine artery embolization, with resolution of the
      vascular mass and resumption of regular menstrual flow. CONCLUSION: AVM in a
      bicornuate uterus is rarely reported. Selective uterine artery embolization
      offers an effective modality of treatment.

PMID- 15730177
TI  - Pruritic urticarial papules and plaques of pregnancy presenting in the postpartum
      period: a case report.
AB  - BACKGROUND: Pruritic urticarial papules and plaques of pregnancy (PUPPP), also
      known as polymorphic eruption of pregnancy, is the most common dermatosis of
      pregnancy. It usually evolves in the third trimester and resolves rapidly
      postpartum. CASE: A 25-year-old woman complained of an intensely pruritic rash
      for 2 days. The rash began 10 days postpartum. It began on her abdomen and spread
      to her buttocks, legs and upper arms. On examination, erythematous papules and
      urticarial plaques were present in the striae of the abdomen and buttocks and
      involved the legs, arms and back. No excoriations, vesicles or pustules were
      present, and there was sparing of the face, palms and soles. The patient was
      treated with fexofenadine, hydroxyzine, oatmeal baths and cool compresses. Follow
      up 2 days later revealed a worsening rash and persistence of severe pruritus. At
      that time the patient was placed on prednisone, which led to relief of her
      symptoms and clearing of the rash. DISCUSSION: PUPPP is reported to develop in
      0.5% of pregnancies. MEDLINE searches of the literature from 1966 to 2003 using
      the keywords pruritic urticarial papules and plaques of pregnancy or polymorphic
      eruption of pregnancy and postpartum revealed only 2 other cases of PUPPP
      developing in the postpartum period. Although the clinical presentation of this
      patient was typical of that of PUPPP, it demonstrates an unusual time course with
      its postpartum presentation. CONCLUSION: Dermatoses of pregnancy should remain in
      the differential diagnosis of rash even weeks after a woman delivers.

PMID- 15730178
TI  - Prenatal corticosteroid therapy for elevated liver enzyme/low platelet count
      syndrome: a case report.
AB  - BACKGROUND: Early preterm onset of elevated liver enzymes/low platelet count
      (ELLP) syndrome poses a significant management problem. CASE: Antepartum
      methylprednisolone, 40 mg/d intravenously was employed to stabilize ELLP
      syndrome, to achieve fetal lung maturity and to postpone delivery at 25 weeks and
      5 days' gestation. Normalization of the liver transaminases and platelet count
      occurred with the use of corticosteroids, but sudden fetal death occurred at 28
      weeks and 2 days' gestation. CONCLUSION: Prenatal corticosteroids may improve the
      biochemical and hematologic parameters of ELLP syndrome but may result in
      intrauterine death.

PMID- 15730179
TI  - Sjogren's syndrome diagnosed in pregnancy: a case report.
AB  - BACKGROUND: As in most other autoimmune diseases, Sjogren's syndrome is seen
      predominantly in women. Since the peak age is around the late reproductive and
      early postmenopausal period, the obstetric aspect has not been well studied.
      CASE: A 28-years-old woman, pregnant for 22 weeks and 5 days, was admitted with
      worsening general status, skin lesions, arthralgias, and oral and ocular symptoms
      typical of Sjogren's syndrome. She underwent hemodialysis for renal
      insufficiency. To prevent autoantibody formation, progression of the disease,
      therapy with methyl prednisolone, 100 mg/d intravenously; cyclophosphamide, 500
      mg/month in a single intravenous application; hemodialysis 3 times a week; and
      plasmapheresis 7 times was instituted. An 1,100-g, male infant at 27 weeks and 5
      days was delivered by cesarean section because of premature preterm rupture of
      membranes and severe late decelerations on cardiotocography. The infant was
      discharged from the neonatal intensive care unit after 30 days, weighing 1,800 g.
      Postnatal echocardiographic examination of the infant revealed neither cardiac
      malformations nor arrhythmias. CONCLUSION: Since the presence of autoantibodies
      against SS-A and SS-B are reported to accompany congenital heart block, the
      primary goal of therapy should be preventing this untoward effect of the disease.
      Close monitoring during pregnancy is mandatory to detect preeclampsia,
      intrauterine growth retardation and preterm labor.

PMID- 15730180
TI  - Prayer and the success of IVF.

PMID- 15730182
TI  - President Kerr's message.

PMID- 15730183
TI  - Behind the scenes, surgical unit treats Fallujah's casualties.

PMID- 15730181
TI  - JPN interviews president of new Nursing Organization.

PMID- 15730184
TI  - Reducing relocation stress syndrome in long-term care facilities.

PMID- 15730185
TI  - Geriatric pharmacology: drugs used in the management of diabetes mellitus.

PMID- 15730186
TI  - Colorimetric analysis of protein sulfhydryl groups in milk: applications and
      processing effects.
AB  - Methods for protein sulfhydryl (SH) group analysis in food systems have been
      largely overlooked. Nevertheless, changes in SH group concentration affect both
      physical and nutritional characteristics of high protein foods and ingredients.
      Food scientists and technologists require improved understanding of protein SH
      chemistry in order to design processes that minimize loss of thiol groups. This
      article surveys colorimetric methods for food protein SH group analysis with
      applications to fluid milk and dried milk powder. Most colorimetric assays
      (chloromeribenzoate, pyridine disulfide, Nitrobenzo-2-oxa-1,3-diazole, papain
      reactivation assay, etc.) were found to be inferior to the Ellman method based on
      the use of 5,5'dithio (bis-2 nitro benzoic acid). Techniques for SH group
      analysis in fluid milk and dried milk powder are described, along with typical
      results, their interpretations, and current research related to processing
      effects and the role of milk SH content on a wider range of technological issues,
      such as development of cooked flavors, fouling and cleaning of plate heat
      exchanges, protein-protein interactions, and the storage stability. Finally, a
      number of areas requiring further research are presented.

PMID- 15730187
TI  - Quality and safety aspects of PEF application in milk and milk products.
AB  - The articles published to date on the possibilities of applying the new PEF
      technology to milk and milk products are summarized in a review that presents
      them in chronological order and grouped on the basis of the factor studied
      (microorganism, enzyme, quality parameter, or shelf-life). An accompanying table
      shows details of the equipment and process corresponding to each article in
      chronological order.

PMID- 15730188
TI  - Coordinate contribution of lipid oxidation and Maillard reaction to the
      nonenzymatic food browning.
AB  - Lipid oxidation and the Maillard reaction are probably the two most important
      reactions in Food Science. Both include a whole network of different reactions in
      which an extraordinary complex mixture of compounds are obtained in very
      different amounts and produce important changes in food flavor, color, texture,
      and nutritional value, with positive and negative consequences. This article
      analyzes the interactions between both reactions, with special emphasis in
      nonenzymatic browning development, by discussing the influence of lipid oxidation
      products in the Maillard pathway and vice versa, as well as the existence of
      common intermediates and polymerization mechanisms in both reactions. The
      existing data suggest that both reactions are so interrelated that they should be
      considered simultaneously to understand the products of the Maillard reaction in
      the presence of lipids and vice versa, and should be included in one general
      pathway that can be initiated by both lipids and carbohydrates.

PMID- 15730189
TI  - Challenges in the addition of probiotic cultures to foods.
AB  - Probiotic cultures are increasingly being added to foods in order to develop
      products with health-promoting properties. Although the literature is abundant on
      the beneficial effects of bifidobacteria and Lactobacillus acidophilus on health,
      little information is available on the challenges industry faces in adding these
      probiotic cultures to food products. The aim of this article is to examine seven
      issues that should be addressed when developing functional foods: 1) type or form
      of probiotic that should be used; 2) addition level required to have a beneficial
      effect; 3) toxicity; 4) effect of the processing steps on viability; 5)
      determination, in the product, of the cell populations added; 6) stability during
      storage; 7) changes in sensory properties of the foods.

PMID- 15730190
TI  - Wrapping up. Closing arguments end in Tenet kickback case.

PMID- 15730191
TI  - States of emergency. As fiscal challenges increasingly overwhelm their budgets,
      states brace for the Bush administration's Medicaid plan.
AB  - With a host of other expensive issues leading President Bush's agenda, officials
      fear Medicaid could suffer some hard blows. States are already carving out
      efficiencies, even as enrollment swells. New HHS Secretary Mike Leavitt, left,
      last week said he saw an opportunity to revamp coverage for some Medicaid
      recipients. "Wouldn't it be better to give Chevys to everyone, rather than
      Cadillacs to a few?" he asked.

PMID- 15730192
TI  - It's a seller's market. Insurers turn to managed care.

PMID- 15730193
TI  - Trusting leadership. Governance education available to trustees.

PMID- 15730194
TI  - Price of leadership. Execs reap financal perks while serving on board.

PMID- 15730195
TI  - Paid to perform. CMS announces first bonus program for doctors.

PMID- 15730196
TI  - On the agenda. State of the Union address stresses malpractice issue.

PMID- 15730197
TI  - Making a leap. Deal puts Extendicare in top five for assisted living.

PMID- 15730198
TI  - Unwelcome advance. Beverly Enterprises rejects unsolicited buyout offer.

PMID- 15730199
TI  - Audit condemns Fairview. Minn. attorney general calls billingpractices illegal.

PMID- 15730200
TI  - L.A.'s loss. Drew/King is stripped of ICAHO accreditation.

PMID- 15730201
TI  - Cynicism or realism? Is true reform behind the president's support of healthcare
      IT?

PMID- 15730202
TI  - Team effort. McLeod uses 'patient rounds,' leadership meetings to boost quality.

PMID- 15730203
TI  - Upon further review. 'External review' of medical claim denials is now the law of
      the land nearly nationwide. But the system has its fans and foes.

PMID- 15730204
TI  - By the numbers. Largest healthcare law firms ranked by total membership in the
      American Health Lawyers Association.

PMID- 15730205
TI  - The Abu Ghraib scandal you don't know.

PMID- 15730206
TI  - Social Security: the 4 percent solution.

PMID- 15730207
TI  - Going private. Lessons from overseas.

PMID- 15730208
TI  - The power of make-believe.

PMID- 15730210
TI  - [Diagnostics and treatment of ventilator-associated bronchopneumonia at a
      coronary unit].
AB  - Ventilator-associated pneumonia represents a severe complication in patients who
      are receiving mechanical ventilation. The incidence is presumed to be 25% of the
      total number of mechanically ventilated patients. The clinical assessment is
      usually based on the presence of a new radiographic infiltrate, fever, blood
      leukocytosis, or leukopenia and purulent tracheal secretions. According to the
      time after tracheal intubation when VAP occurs we can distinguish early and late
      onset VAP, which differs in terms of infectious agent. The early and adequate
      antibiotic therapy together with the basic preventive treatment represents the
      only possibility to avoid the complications. The article reviews the actual
      knowledge of this phenomenon, the adequate diagnostic attitudes and therapeutic
      possibilities.

PMID- 15730209
TI  - [Apolipoprotein AV and triglyceridemia].
AB  - High plasma triglyceride levels have been suggested to be independent risk
      factors of cardiovascular disease development and cardiovascular diseases are the
      most common cause of death in industrial countries around the world. It is known,
      that plasma levels of triglycerides are partially genetically determined. The
      importance of apoAV gene for determination of plasma triglyceride levels has been
      suggested by creations of transgenic and knock-out mice and confirmed on
      population studies. More then ten variants have been described in the human apoAV
      gene. Associations between four of them (T-1131-->C, Serl19-->Trp, Val153-->Met a
      Cys185-->Gly) and plasma triglyceride levels have been intensively analysed in
      different populations. Although with some differences between ethnic groups,
      alleles C-1131, Trp19 a Cys185 (so far detected just in Chinese population) are
      connected with elevated levels of plasma triglycerides. First analysis have
      detected that T-11131-->C a Ser19-->Trp apoAV variants could influence risk of
      myocardial infarction and size of LDL particles. Val153-->Met polymorphism is not
      associated with plasma levels of triglycerides, but females homozygous for Val153
      have elevated levels of plasma HDL cholesterol.

PMID- 15730212
TI  - [Non-alcoholic risks of alcoholic beverages].
AB  - Alcoholic beverages are a potential source of numerous health risks. The general
      risks are well known; first of all they result from the contents of the alcohol
      and their degree is directly proportional to the amount consumed. However,
      alcoholic beverages contain also a wide range of non-alcoholic components, which
      can be a source of health risks as well. Some of these substances work through
      allergic or pseudoallergic mechanisms and such undesired response can appear
      early after the consumption of a small amount of beverage. The article offers a
      basic survey of alcoholic beverages; it mentions important technological
      procedures of their production stating also the most significant resulting
      components of their individual types. A special attention is paid to the non
      alcoholic components, which can be the cause of undesired effects on the human
      health.

PMID- 15730211
TI  - [Significance of mitochondria in the heart muscle].
AB  - Besides their traditional role as the energy factory of the cell, mitochondria
      play an important role in other aspects of cardiac cell functioning under
      physiological and pathological conditions. They are involved in the regulation of
      calcium homeostasis, production of reactive oxygen species as well as in the
      process of cardiac cell death. Recently, the interest in their participation in
      ischemia-reperfusion injury and potential role in cardioprotective mechanisms,
      with particular attention to developmental aspects has markedly increased.

PMID- 15730213
TI  - [Contribution of the evidence-based medicine to the solution of some problems in
      electrocardiography].
AB  - The paper summarizes the author's view on the possibilities to use the principles
      of evidence-based medicine for the re-evaluation of classical hypotheses and
      formulation of new hypotheses in electrocardiology. Electrocardiographic
      diagnostics of the left ventricular hypertrophy based on the voltage criteria,
      which is known to suffer by high number of so-called false negative results and
      low sensitivity, is shown as an example. An alternative approach is presented,
      based on the acceptation of these so-called false negative results as true
      results, reflecting changes in electrical properties of myocardium due to
      electrophysiological remodeling in left ventricular hypertrophy. In this context
      a new parameter is introduced for the quantification of the relative voltage
      deficit--the specific potential of myocardium. Results of experimental and
      clinical studies supporting the new paradigm are presented.

PMID- 15730214
TI  - [Signs of active infection with Chlamydia pneumoniae in patients with coronary
      heart disease].
AB  - BACKGROUND: Possible relationship between Chlamydia pneumoniae (CPN) infection
      and atherosclerosis has been documented in many seroepidemiological, histological
      and biological studies. The objectives of the present study were to find out
      whether serological signs of active CPN infection in patients with coronary heart
      disease (CHD) are associated with the presence of bacterial DNA in peripheral
      blood and to correlate with clinical symptoms and to study the dynamics of the
      markers of CPN infection within a six-month follow-up. METHODS AND RESULTS:
      Seventy-one patients with acute CHD were enrolled in the study. They underwent
      clinical and biochemical tests and were screened for the presence of genus- and
      type-specific IgG, IgA and IgM antibodies against CPN at admission and then in 3-
      and 6-month intervals. CPN DNA was detected in peripheral blood using nested PCR.
      Serological markers of active CPN infection were found in 36 patients (51.4%)
      while bacterial DNA was detected in two patients only. Laboratory signs of active
      CPN infection did not correlate with either clinical symptoms or levels of
      biochemical markers. In most of the patients, titers of anti-CPN antibodies were
      stable throughout the follow-up. Increase in antibody titers was observed in 23%
      of patients and was associated with more frequent signs of unstable angina
      pectoris (p=0.06) but not with higher risk of myocardial infarction within 6
      months after the acute episode of CHD. CONCLUSIONS: In patients with CHD,
      serological markers of active infection persist for a long time. Nevertheless,
      their association with the course of CHD or relapse risk was not proved.
      Bacterial DNA was rarely detected in peripheral blood of the patients. None of
      the currently available laboratory tests proved adequately effective for
      detection of ongoing or chronic CPN infection. This project was sponsored by
      grant IGA MZ CR NI/6811-3 and research plan of Natl. Inst.Publ.Health

PMID- 15730215
TI  - [Resistance of Mycobacterium tuberculosis to antituberculotic drugs in Czech
      Republic in 2003].
AB  - BACKGROUND: The results of Mycobacterium tuberculosis susceptibility testing in
      2003 were analysed in 568 (84%) pulmonary TB definite cases in the Czech
      Republic. METHODS AND RESULTS: The resistance on antituberculotic drugs was
      detected in 4.9% of TB bacilli. Most frequently, resistance on one drug-
      isoniazid (1.8% of pulmonary TB definite cases) has been observed. Multidrug
      resistant TB was found in two cases in 2003. CONCLUSIONS: The resistance of
      Mycobacteria was found significantly more often in foreign-born persons with
      pulmonary TB (25% of strains of TB bacilli were resistant on one or more AT
      drugs). Resistance on AT drugs was more frequent also in previously treated TB
      cases, especially if the relapse occurred after 3,5 years after finishing
      previous treatment.

PMID- 15730216
TI  - [Metabolic syndrome and latent depression in the population sample].
AB  - BACKGROUND: The aim of study was to reveal the relationship between metabolic
      syndrome and depression in a population sample, based on clinical and metabolic
      parameters. METHODS AND RESULTS: We tried to estimate depression (or other
      psychopathologies) prevalence in a randomly chosen population sample of the
      Pilsen city, using special questionnaires. Further, we estimated metabolic
      syndrome of insulin resistance risk factors and we looked for the relationship
      between these two disorders. Mental state of object was classified according to
      the questionnaires results, currently evaluated by the psychiatrist. Metabolic
      syndrome of insulin resistance was diagnosed as a presence of 3 of the 5
      following factors: Triglycerides > or = 1.7 mmol/l, HDL cholesterol < 1.0 mmol/l
      in males or < 1.3 mmol/l in females, blood pressure > or = 130/85 mmHg (and/or
      antihypertensive medication), fasting plasma glucose > or = 6.1 mmol/l, waist
      circumference >102 cm in males or > 88 cm in females. Depressive syndrome
      diagnosed by Zungs scale is present in 31% of the Pilsen population, in 38%
      females and 31% males (n = 340). In the group of depressive objects,
      characteristics of metabolic syndrome of insulin resistance were two times higher
      than in the control group. Differences in resting heart rate, triglycerides level
      and fasting C-peptid were significantly higher in the depressive subjects. After
      the corrections considering age, sex and treatment adjustment, the waist to hip
      ratio was in the depressive subjects statistically higher as well as the 24 hour
      excretion of urine cortisone. In persons with metabolic syndrome of insulin
      resistance the prevalence of depression and anxiety was significantly higher.
      CONCLUSIONS: Our results show a possible relationship between depressive disorder
      and risk factors of the syndrome of insulin resistance. The question remains if
      the depression treatment can correct some of the metabolic syndrome risk factors.

PMID- 15730217
TI  - [Inter-individual variability of gene expression detected by biochips].
AB  - BACKGROUND: For gene expression profiling in leukemia patients we use array
      technologies in our laboratory. The assays are based on the comparison of patient
      and control expression profiles. Expression profile of the control sample should
      be representative but there is a problem of inter-individual variability in
      population, because also healthy persons display differences in gene
      transcription activity. Aim of the study was to characterize expression profiles
      of controls and to determine variability rate. METHODS AND RESULTS: The control
      group comprised 15 "healthy" persons (9 peripheral bloods, 2 bone marrows, 4 cord
      bloods) from various age categories (0 to 56 years). Expression profiles were
      detected using Atlas Human Cancer cDNA Expression Arrays (Clontech) with 588 gene
      probes. Total RNAs were isolated from leukocytes and were reverse transcribed
      into cDNA. Out of 588 tested genes on average 24% were detected. Inter-individual
      variability of gene expression profiles of leukocytes from the same tissue did
      not exceed 25%. Majority of the genes, with significant changes in leukemia
      patients, was expressed at similar level in the control group, with the exception
      of bone marrow and cord blood samples that demonstrated higher expression of
      PCNA, MMP8, MMP9 genes. In bone marrow high PCNA expression could result from
      active cell proliferation in this tissue. Strong expressions of MMP8 and MMP9
      might be associated with the presence of cell precursors because there were not
      detected in peripheral blood leukocytes. Expression of some genes was tissue
      specific or followed "ontogenetic" trend. CONCLUSIONS: The inter-individual
      expression variability has to be taken into account in expression comparative
      analyses. In order to minimize the influence of existing variability we use mixed
      control samples and statistical data processing.

PMID- 15730218
TI  - [Indication for the treatment of Helicobacter pylori infection].
AB  - Helicobacter pylori is a microorganism that is thought to play a role in the
      etiopathogenesis of peptic ulcer disease. Eradication of this microorganism is
      valuable clinical cure of infected patients. Efficacious regimens generally
      include an antisecretory agent combined with two antimicrobials. The main
      determinant of overall cost of treatment is the rate of eradication of the
      microorganism. Resistance can occur to the commonly used antibiotics but can
      usually be overcome with an altered regimen. It is important for care physicians
      to clearly understand indication and how to select appropriate therapy against
      Helicobacter pylori infection.

PMID- 15730219
TI  - [Sexual asphyxias in medical practice].
AB  - The authors deal with so called sexual hanging. From literary historical dates
      concerning this problem they give a case of Czech musician named Kotzwarra. The
      typical autoerotic fatalities and atypical autoerotic fatalities are mentioned.
      The article sums up basic characteristics during the investigation of the scene
      of a sexual hanging.

PMID- 15730220
TI  - [Information explosion in a better light after fifty years].
AB  - The phenomenon of "Information explosion" emerged in the professional and later
      also in the unprofessional community in the middle of the twentieth century. It
      expresses feeling of an unexpected general congestion with increasing number of
      published articles and books, which are not possible to go through, process and
      use in the real time. Unexpected development of the science after the Second
      World War resulted in unusually high production of new data and information.
      Their fast release was enabled by modernization of the publication process
      together with an increase of the number of scientific journals. Despite the
      relative information isolationism during the totalitarian regiment, this
      worldwide process soon emerged also in our region. However, the overload in
      information was not balanced by modernization of methods in the bibliographic and
      librarian systems, which could bring the new information to the scientific
      community. The turning point in the transfer of information was the development
      of worldwide interconnection - the word wide web or the Internet. For the
      processing of new information it was possible to introduce gradually still more
      powerful information technologies based on computers with on-line connection to
      the Internet. To solve the information explosion it was necessary to possess such
      technology and necessary programs and to master the elements of information and
      computer know-how. Contemporary modern technology with various user-friendly
      search engines, catalogues, repositories, and with voluminous bibliographic
      databases enable the use of full-text sources and give a better view on the
      formerly catastrophically looking information explosion. Along with that it is
      necessary to find financial sources to cover the access to the system.
      Information support of the scientific work based on such possibilities represents
      in the brim of modern information society the only possibility of effective
      activity in any field. It is also a good way how to precede the possible next
      information overload.

PMID- 15730221
TI  - [Alcohol-related amnesia ("blackout") in broader perspective].
AB  - Alcohol-related amnesia ("blackout") is a common even in people who are not
      alcohol dependent. The average duration of simple alcohol-induced amnesia in our
      alcohol dependent male patients was almost 8 hours (7.96, SD=23.96). Alcohol
      induced amnesia is considered to be a risk factor for long-term impairment of
      cognitive functions, if alcohol abuse continues. On the other hand cognitive
      functions in alcohol dependent persons who abstain from alcohol often improve
      remarkably because of reorganisation and restoration of neuronal networks. This
      process can be enhanced by vitamin B1, appropriate treatment of withdrawal
      syndrome, memory training, coping with stress and depression (relaxation
      techniques can be used), balanced life-style, and nootropic drugs. Alcohol
      related amnesia often motivates alcohol dependent patients to overcome their
      problem, especially if it is appropriately used in psychotherapy.

PMID- 15730222
TI  - [ABC of smoking cessation. Bupropion and other drugs in non-nicotine therapy].
AB  - Administration of bupropion is the most effective and safe non-nicotine therapy
      of tobacco dependence. It doubles the success rate, similarly as nicotine
      replacement therapy. In heavy dependent smokers combination of both mentioned
      therapies is recommended. From other antidepressant drugs, nortripyline is
      effective, and then clonidine and mecamylamine. But their effect is restricted.

PMID- 15730223
TI  - [Thirty years of the balloon catheter--A. Gruntzig and percutaneous balloon
      angioplasty].
AB  - Percutaneous transluminal coronary angioplasty--PTCA--will forever be linked with
      A. Gruentzig's name. Building on the work of Charles Dotter and Malvin Judkins be
      developped novel technique of revascularisation and established a new speciality 
      interventional cardiology. The aim of this article is to sum up the most
      important data on Gruentzig's revolutionary work. Andreas Roland Gruentzig was
      born on June 25, 1939 in Dresden, Germany. In 1957 he received his B. A. in
      Leipzig (German Democratic Republic). In 1958, Andreas emigrated to the German
      Federal Republic, received another B. A. in Heidelberg, and entered the Medical
      School in Heidelberg where he qualified in 1964. In 1969 he moved to Zurich,
      Switzerland, in the Dept of Angiology of the University Hospital. He soon
      appreciated the potential of recanalising partially occluded lower limb arteries
      using the Dotter-Judkins catheter but also recognised its risks. In 1972-1973 he
      developped his balloon catheter and performed the first femoral angioplasty in
      February 12, 1974, and in January 23, 1975 the first one using his new double
      lumen catheter. The first experimental coronaroplasty in a dog followed in
      September 24, 1975. He presented his results with balloon catheters in November
      15, 1976 in Miami. After a further period of arduous experimental research--stil
      manufacturing the catheters with his small crew in the kitchen--he dilated a
      stenosed coronary artery in a 37-year-old man on September 16, 1977 in Zurich,
      with immediate relief of symptoms. The results of PTCA in five first patients
      were published in the February 14, 1978 issue of Lancet; the coronarography in
      the first patient, on April 10, 2000, revealed normal patency of the site that
      had been dilated (Prof. B. Meier, Bern). However, the news in Zurich 1978 was
      received with a certain incredulity and Gruentzig was unable--in spite of
      Professor A. Senning's support--to obtain facilities to expand his research
      program and clinical activities. In September 1980 he accepted the Chair of
      Medicine (Cardiology) and Radiology with the additional title of Director of the
      Dept of Interventional Cardiology at Emory University in Atlanta, Georgia. Prof.
      Hurst gave him half of his office suite at Emory and later even further
      facilities to expand his program. Here, at Emory, Gruentzig gave 10 angioplasty
      courses and performed with Dr. S. King and Dr. J. Douglas 5000 PTCAs till 1985.
      Before reaching the peak of his scientific carrier, he died in a flying accident,
      with his second wife Margareth Ann, near Forsythe, Monroe County, Georgia, on
      October 27, 1985. His work was appreciated in tributes from the U.S.A., U.K.,
      Switzerland and Germany, by many international awards and honors; numerous
      interventional laboratories in the world carry A. R. Gruentzig's name.

PMID- 15730224
TI  - [Health and money].

PMID- 15730225
TI  - [Remarks to the discussion of prof. MUDr. Stepan Svacina, DrSc., "Medical
      faculties and general/practical medicine in the Czech Republic"].

PMID- 15730227
TI  - [QT interval and its obliqueness].

PMID- 15730229
TI  - Blood pressure regulation and vegetarian diets.
AB  - Hypertension affects approximately 50 million individuals in the United States
      and approximately 1 billion worldwide. Although heredity plays a role in blood
      pressure variability, diet and lifestyle exert considerable influence in blood
      pressure regulation. This report reviews the evidence of the relationship between
      a vegetarian diet and blood pressure regulation and presents data as to the
      putative mechanisms of action.

PMID- 15730230
TI  - Obesity, lutein metabolism, and age-related macular degeneration: a web of
      connections.
AB  - Age-related macular degeneration (AMD) is a major cause of visual impairment in
      the United States. Currently there is no effective cure for this disease. Risk
      factors include decreased lutein and zeaxanthin status and obesity. Obesity is
      also an increasing public health concern. The alarming increase in the prevalence
      of obesity further exacerbates the public health concern of AMD. The mechanism by
      which obesity increases the risk of AMD may be related to the physiologic changes
      that occur with this condition. These include increased oxidative stress, changes
      in the lipoprotein profile, and increased inflammation. These changes would also
      result in an increased destruction and a decreased circulatory delivery of lutein
      and zeaxanthin to the macula of the eye. Therefore, the mechanism by which
      obesity is related to AMD risk may be through indirect effects on changes in
      lutein and zeaxanthin status and metabolism.

PMID- 15730231
TI  - Lunasin: a cancer-preventive soy peptide.
AB  - Lunasin is a novel, cancer-preventive peptide whose efficacy against chemical
      carcinogens and oncogenes has been demonstrated in mammalian cells and in a skin
      cancer mouse model. Isolated and characterized in soy, lunasin peptide is also
      documented in barley. Lunasin is found in all of the genotypes analyzed from the
      US soy germ plasm collection and in commercially available soy proteins. Pilot
      studies show that lunasin is bioavailable in mice and rats when orally ingested,
      opening the way for dietary administration in cancer prevention studies. Lunasin
      internalizes into mammalian cells within minutes of exogenous application, and
      localizes in the nucleus after 18 hours. It inhibits acetylation of core histones
      in mammalian cells. In spite of its cancer-preventive properties, lunasin does
      not affect the growth rate of normal and established cancer cell lines. An
      epigenetic mechanism of action is proposed whereby lunasin selectively kills
      cells being transformed or newly transformed by binding to deacetylated core
      histones exposed by the transformation event, disrupting the dynamics of histone
      acetylation-deacetylation and leading to cell death.

PMID- 15730232
TI  - The effect of weight loss on a stable biomarker of inflammation, C-reactive
      protein.
AB  - Inflammation is pivotal in all phases of atherosclerosis. Increasing body weight
      is positively associated with inflammation. Weight loss studies have shown that
      decreasing body weight significantly decreases C-reactive protein, the prototypic
      biomarker for inflammation. Reducing inflammation through weight loss could
      therefore be associated with reduced risk for cardiovascular disease and other
      obesity-associated chronic diseases.

PMID- 15730233
TI  - Homocysteine and osteoporotic fracture risk: a potential role for B vitamins.
AB  - Hyperhomocysteinemia (elevated plasma homocysteine levels) has been linked to
      increased risk of neural tube defects, cardiovascular disease, Alzheimer's
      dementia, pregnancy complications, and inflammatory bowel disease. Evidence for a
      role of hyperhomocysteinemia in the etiology of osteoporosis has recently been
      strengthened by the findings of two separate studies, which both reported that
      high homocysteine levels significantly increased risk of osteoporotic fracture.
      While the etiology of hyperhomocysteinemia is considered to be multifactorial
      (including genetic, nutritional, and lifestyle factors), a deficiency of one or
      more B vitamins certainly has a role. These vitamins are involved in the
      metabolism and clearance of homocysteine, and thus may have a protective effect
      against osteoporotic fracture risk.

PMID- 15730234
TI  - Dietary diversity in the Japanese national dietary guidelines.

PMID- 15730235
TI  - Synthesis and characterization of the 7-(4-aminomethyl-1H-1,2,3-triazol-1-yl)
      analogue of kabiramide C.
AB  - The 7-(4-aminomethyl-1H-1,2,3-triazol-1-yl) analogue of kabiramide C (5) was
      synthesized by using the Mitsunobu reaction and 1,3-dipolar cycloaddition. This
      compound and the intermediate compounds 2 and 4 were shown to bind tightly to G
      actin in a 1:1 complex and exhibited the same degree of cytotoxicity as 1.
      Compound 5 serves as a key intermediate for the synthesis of actin-directed
      optical probes and drugs.

PMID- 15730236
TI  - Comparative analysis of a neurotoxin from Calliostoma canaliculatum by on-line
      capillary isotachophoresis/1H NMR and diffusion 1H NMR.
AB  - NMR spectroscopy has been coupled on-line to capillary isotachophoresis (cITP) to
      enhance structural analyses of dilute charged species through separation and
      sample concentration. Microcoils, the most mass-sensitive NMR probes available,
      provide optimal detection for cITP/NMR. To evaluate the utility of cITP/NMR for
      natural product analysis, a homogenate of the hypobranchial gland from the marine
      snail Calliostoma canaliculatum containing a cationic neurotoxin (1, a disulfide
      bonded dimer of 6-bromo-2-mercaptotryptamine) was studied. For comparison,
      hypobranchial gland homogenate was also examined by diffusion-NMR, an alternative
      approach for NMR mixture analysis. cITP/NMR concentrated the neurotoxin by almost
      20-fold and isolated it from some of the other components present in the matrix.
      However, a minor component, likely a precursor or degradant, co-migrated with
      compound 1. Diffusion-NMR also did not resolve the two, indicating that the
      compounds possessed similar diffusion coefficients and electrophoretic
      mobilities. The strengths and limitations of the two approaches for NMR mixture
      analysis are discussed.

PMID- 15730237
TI  - Identification of radical scavenging compounds in Rhaponticum carthamoides by
      means of LC-DAD-SPE-NMR.
AB  - A hyphenated LC-DAD-SPE-NMR setup in combination with on-line radical scavenging
      detection has been applied for the identification of radical scavenging compounds
      in extracts of Rhaponticumcarthamoides. After NMR measurements, the pure
      compounds were infused into a mass spectrometer. The technique enabled selective
      detection and identification of individual radical scavenging compounds without
      any prior off-line chromatographic steps. Seven compounds, namely, quercetagetin
      7-beta-glucopyranoside (1), quercetagetin-7-(6"-acetyl-beta-glucopyranoside) (3),
      6-hydroxykaempferol-7-beta-glucopyranoside (2), 6-methoxykaempferol-3-beta
      glucopyranoside (4), 6-hydroxykaempferol-7-(6"-acetyl-beta-glucopyranoside) (5),
      chlorogenic acid (6), and beta-ecdysone (7), were identified in ethanol or
      aqueous extracts. Compound 5 is a new natural compound. Its radical scavenging
      activity was tested against DPPH radical and was found to be weaker than that of
      the reference antioxidants rosmarinic acid and Trolox.

PMID- 15730238
TI  - New colchicinoids from a native Jordanian meadow saffron, colchicum
      brachyphyllum: isolation of the first naturally occurring dextrorotatory
      colchicinoid.
AB  - As part of our continuing investigation of Jordanian Colchicum species, the
      biologically active components of Colchicum brachyphyllum were pursued. Using
      bioactivity-directed fractionation, nine colchicinoids were isolated and
      characterized. One of these has a novel ring system, to which we have ascribed
      the trivial name (+)-demecolcinone (9), and it represents the first naturally
      occurring dextrorotatory colchicinoid. Another isolated compound was a new
      colchicinoid analogue, (-)-2,3-didemethyldemecolcine (8), while the remaining
      seven known colchicinoids were new to the species: (-)-colchicine (1), (-)-3
      demethylcolchicine (2), (-)-cornigerine (3), beta-lumicolchicine (4), (-)
      androbiphenyline (5), (-)-demecolcine (6), and (-)-3-demethyldemecolcine (7). The
      brine shrimp lethality test was used to direct the isolation of these
      colchicinoids. Moreover, all pure compounds were evaluated for cytotoxicity
      against a human cancer cell panel, for antimicrobial activity in an array of
      bacteria and fungi (including yeast), and for their potential to be allosteric
      modulators of the gamma-aminobutyric acid type A receptor.

PMID- 15730239
TI  - (-)-Echinobetaine A: isolation, structure elucidation, synthesis, and SAR studies
      on a new nematocide from a southern Australian marine sponge, Echinodictyum sp.
AB  - A nematocidal agent present in a southern Australian marine sponge of the genus
      Echinodictyum has been isolated and identified by detailed spectroscopic analysis
      and total synthesis as the novel betaine (-)-echinobetaine A (6). Preliminary SAR
      investigations have been undertaken.

PMID- 15730240
TI  - New bioactive clerodane diterpenoids from the bark of Casearia grewiifolia.
AB  - Bioactivity-guided fractionation of hexane and dichloromethane extracts of the
      bark of Casearia grewiifolia afforded four new clerodane diterpenes,
      caseargrewiins A-D (1-4), and two known clerodane diterpenes, rel
      (2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2
      methylbutanoyloxy)cleroda-3,13(16),14-triene (5) and rel
      (2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-hydroxy-2-(2
      methylbutanoyloxy)cleroda-3,13(16),14-triene (6). The structures of 1-4 were
      established on the basis of the interpretation of their 1D and 2D NMR spectral
      data. The absolute configuration of 4 was determined by the modified Mosher's
      method. All compounds exhibited promising antimalarial and antimycobacterial
      activities but also cytotoxicity against three cancer cell lines.

PMID- 15730241
TI  - Bioactive constituents from Boswellia papyrifera.
AB  - Phytochemical investigation of the stem bark extract of Boswellia papyrifera
      afforded two new stilbene glycosides, trans-4',5-dihydroxy-3-methoxystilbene-5-O
      {alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D
      glucopyranoside (1), trans-4',5-dihydroxy-3-methoxystilbene-5-O-[alpha-L
      rhamnopyranosyl-(1-->6)]-beta-D-glucopyranoside (2), and a new triterpene, 3alpha
      acetoxy-27-hydroxylup-20(29)-en-24-oic acid (3), along with five known compounds,
      11-keto-beta-boswellic acid (4), beta-elemonic acid (7), 3alpha-acetoxy-11-keto
      beta-boswellic acid (8), beta-boswellic acid (9), and beta-sitosterol (10). The
      stilbene glycosides exhibited significant inhibition of phosphodiesterase I and
      xanthine oxidase. The triterpenes (3-9) exhibited prolyl endopeptidase inhibitory
      activities.

PMID- 15730242
TI  - Asimitrin and 4-hydroxytrilobin, new bioactive annonaceous acetogenins from the
      seeds of Asimina triloba possessing a bis-tetrahydrofuran ring.
AB  - Bioactivity-directed fractionation of the seeds of Asimina triloba resulted in
      the isolation of asimitrin (1) and 4-hydroxytrilobin (2). Compound 1 represents
      an adjacent ring-hydroxylated bis-tetrahydrofuran (THF) acetogenin. Compound 2
      has an adjacent bis-THF ring with two flanking hydroxyl groups and a alpha,beta
      unsaturated gamma-lactone with a 4-hydroxyl group. Compounds 1 and 2 showed
      cytotoxic selectivity, with 100-10 000 times the potency of adriamycin against
      prostate adenocarcinoma (PC-3) and colon adenocarcinoma (HT-29) cell lines.

PMID- 15730244
TI  - Antineoplastic agents. 527. Synthesis of 7-deoxynarcistatin, 7-deoxy-trans
      dihydronarcistatin, and trans-dihydronarcistatin 1(1).
AB  - The synthesis of sodium narcistatin (8) was improved (88% overall yield) and the
      modified reaction sequence was utilized to synthesize three new 3,4-cyclic
      phosphate prodrugs, sodium 7-deoxynarcistatin (5), sodium 7-deoxy-trans
      dihydronarcistatin (6), and sodium trans-dihydronarcistatin (7). The human cancer
      cell line inhibitory isocarbostyril precursors were isolated from the bulbs of
      Hymenocallis littoralis obtained by horticultural production or reduction of
      narciclasine (1a --> 4) from the same source.

PMID- 15730243
TI  - Three new triterpenes from Nerium oleander and biological activity of the
      isolated compounds.
AB  - New ursane-type triterpene 1, oleanane-type triterpene 2, and dammarane-type
      triterpene 15 were isolated from the leaves of Nerium oleander together with 12
      known triterpenes, 3beta-hydroxy-12-ursen-28-oic acid (ursolic acid, 3), 3beta,27
      dihydroxy-12-ursen-28-oic acid (4), 3beta,13beta-dihydroxyurs-11-en-28-oic acid
      (5), 3beta-hydroxyurs-12-en-28-aldehyde (6), 28-norurs-12-en-3beta-ol (7), urs-12
      en-3beta-ol (8), urs-12-ene-3beta,28-diol (9), 3beta-hydroxy-12-oleanen-28-oic
      acid (oleanolic acid, 10), 3beta,27-dihydroxy-12-oleanen-28-oic acid (11), 3beta
      hydroxy-20(29)-lupen-28-oic acid (betulinic acid, 12), 20(29)-lupene-3beta,28
      diol (betulin, 13), and (20S,24R)-epoxydammarane-3beta,25-diol (14). On the basis
      of their spectroscopic data, the structures of the new compounds 1, 2, and 15
      were established as 3beta,20alpha-dihydroxyurs-21-en-28-oic acid, 3beta,12alpha
      dihydroxyoleanan-28,13beta-olide, and (20S,24S)-epoxydammarane-3beta,25-diol,
      respectively. The anti-inflammatory activity of the seven isolated compounds and
      methyl esters of ursolic acid and oleanoic acid in vitro was examined on the
      basis of inhibitory activity against the induction of the intercellular adhesion
      molecule-1 (ICAM-1). The anticancer activity of the 14 isolated compounds,
      including 1, 2, 15, and methyl esters of ursolic acid and oleanolic acid in vitro
      was examined on the basis of the cell growth inhibitory activities toward three
      kinds of human cell lines.

PMID- 15730245
TI  - Malettinins B-D: new polyketide metabolites from an unidentified fungal colonist
      of Hypoxylon Stromata (NRRL 29110).
AB  - Malettinins B-D (2-4), three new antimicrobial polyketide-derived metabolites
      related to the previously reported malettinin A (1), have been obtained from
      nonsporulating cultures of an isolate of Mycelia sterilia MYC-155 (= NRRL 29110)
      collected from colonies of Hypoxylon stromata. Malettinins B (2) and C (3) are
      partially reduced analogues of malettinin A and were identified by analysis of
      NMR and MS data. Malettinin D (4) is biogenetically similar, but possesses a new
      ring system, and the structure of 4 was established by single-crystal X-ray
      diffraction analysis.

PMID- 15730246
TI  - Resveratrol derivatives from the roots of Vitis thunbergii.
AB  - Investigating the constituents of the roots of Vitis thunbergii led to the
      isolation of four new resveratrol derivatives, vitisinols A-D (1-4), together
      with (+)-epsilon-viniferin, (-)-viniferal, ampelopsin C, miyabenol A, (+)-vitisin
      A, and (+)-vitisin C. The structures of these 10 compounds were established by
      spectroscopic (NMR and MS) analyses. All of the isolated compounds, except 1,
      were tested for their antiplatelet and antioxidative activities.

PMID- 15730247
TI  - Lignans and their degraded derivatives from Sarcostemma acidum.
AB  - Four lignans, sacidumlignans A-D (1-4), and two degraded lignan derivatives,
      sacidumols A (5) and B (6), along with four known compounds, (+)-pinoresinol,
      9alpha-hydroxypinoresinol, perforatic acid, and peucenine-7-O-methyl ether, were
      isolated from the ethanolic extract of the whole plant of Sarcostemma acidum. The
      structures and relative configuration of these new compounds were elucidated on
      the basis of spectroscopic and chemical data, especially 2D NMR techniques.
      Sacidumlignan D (4) was assigned as a rearranged tetrahydrofuran lignan with an
      unprecedented skeleton. Sacidumlignan A (1) showed moderate antimicrobial
      activities against two Gram-positive bacteria in vitro.

PMID- 15730248
TI  - Characterization of lipophilic pentasaccharides from beach morning glory (Ipomoea
      pes-caprae).
AB  - The hexane-soluble extract from the aerial parts of the herbal drug Ipomoea pes
      caprae (beach morning-glory), through preparative-scale recycling HPLC, yielded
      six lipophilic glycosides, namely, five new pentasaccharides of jalapinolic acid,
      pescaproside A (1) and pescapreins I-IV (2-5), as well as the known stoloniferin
      III (6). Saponification of the crude resin glycoside mixture yielded simonic acid
      B (7) as the glycosidic acid component, whereas the esterifying residues of the
      natural oligosaccharides comprised five fatty acids: 2-methylpropanoic, (2S)
      methylbutyric, n-hexanoic, n-decanoic, and n-dodecanoic acids. Pescaproside A
      (1), an acylated glycosidic acid methyl ester, is related structurally to the
      product obtained from the macrolactone hydrolysis of pescapreins I-IV (2-5). All
      the isolated compounds (1-6), characterized through high-field NMR spectroscopy,
      were found to be weakly cytotoxic to a small panel of cancer cell lines.

PMID- 15730249
TI  - Cytotoxic flavonol glycosides from Triplaris cumingiana.
AB  - Three new compounds, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl
      4,6-bis-O-beta-D-(3,4,5-trihydroxybenzoyl)glucopyranoside (1), 5,7-dihydroxy-2-(4
      hydroxyphenyl)-4-oxo-4H-chromen-3-yl-5-O-alpha-L-(3,4,5
      trihydroxybenzoyl)arabinofuranoside (2), and 2-hydroxy-4-O-alpha-L-(3,5,7
      trihydroxy-4-oxo-4H-chromen-2-yl)phenylarabinofuranoside (3), were isolated from
      the young leaves of Triplaris cumingiana, together with two known compounds,
      quercetin 3-O-alpha-L-(5"-O-galloyl)arabinofuranoside (4) and quercetin 3-O-beta
      D-(6"-O-galloyl)glucopyranoside (5). The structures of 1-3 were established by
      spectroscopic methods. Compounds 1-5 were evaluated for their cytotoxic
      activities against the MCF-7, H-460, and SF-268 human cancer cell lines.

PMID- 15730250
TI  - Glucosinolates in the subantarctic crucifer Kerguelen cabbage (Pringlea
      antiscorbutica).
AB  - Glucosinolates in the subantarctic Kerguelen cabbage (Pringlea antiscorbutica)
      were determined by HPLC. Glucoerucin (6) was present only in the seeds, whereas
      sinigrin (2), gluconapin (3), n-butyl glucosinolate (4), glucoraphanin (1), and
      glucotropaeolin (5) were present in both the seeds and leaves. High
      concentrations of glucosinolates, precursors of bioactive isothiocyanates, were
      found in the leaves of Kerguelen cabbage. In particular, the lack of unhealthy
      beta-hydroxylated aliphatic side-chain glucosinolates is supportive of this
      vegetable being a possible dietary source with a high nutritional value.

PMID- 15730251
TI  - Brevicompanine C, cyclo-(D-Ile-L-Trp), and cyclo-(D-Leu-L-Trp), plant growth
      regulators from Penicillium brevi-compactum.
AB  - New plant growth regulators, named brevicompanine C (1), cyclo-(D-Ile-L-Trp) (2),
      and cyclo-(D-Leu-L-Trp) (3), have been isolated from Penicillium brevi-compactum
      Dierckx, and their structures have been established by spectroscopic methods
      including 2D NMR and chiral TLC analysis. Plant growth activities of 1, 2, and 3
      have been examined using lettuce seedling bioassay methods. All compounds
      accelerated the root growth of the seedlings in proportion to their concentration
      from 1 to 100 mg/L.

PMID- 15730253
TI  - Insect antifeedants from Croton jatrophoides: structures of zumketol, zumsenin,
      and zumsenol.
AB  - Three new A-seco limonoids, zumketol (1), zumsenin (2), and zumsenol (3), were
      isolated from a methanol extract of Croton jatrophoides by bioassay-guided
      fractionation, and their structures were determined by NMR analysis. The alpha
      ketol 1 may be biosynthesized via the intramolecular acyloin condensation of a
      dicarboxylate intermediate.

PMID- 15730252
TI  - Lajollamycin, a nitro-tetraene spiro-beta-lactone-gamma-lactam antibiotic from
      the marine actinomycete Streptomyces nodosus.
AB  - A strain of Streptomyces nodosus (NPS007994) isolated from a marine sediment
      collected in Scripps Canyon, La Jolla, California, was found to produce
      lajollamycin (1), a nitro-tetraene spiro-beta-lactone-gamma-lactam antibiotic.
      The structure was established by complete analysis of spectroscopic data and
      comparison with known antibiotics oxazolomycin (2), 16-methyloxazolomycin (3),
      and triedimycin B (4). Lajollamycin (1) showed antimicrobial activity against
      both drug-sensitive and -resistant Gram-positive bacteria and inhibited the
      growth of B16-F10 tumor cells in vitro.

PMID- 15730254
TI  - Two new cytotoxic linderazulenes from a deep-sea gorgonian of the genus
      Paramuricea.
AB  - The known compound linderazulene (1) and two new linderazulenes (2, 3) were
      isolated from a deep-sea gorgonian Paramuricea sp. The structures of 2 and 3 were
      determined through spectroscopic methods. Compounds 1-3 show moderate in vitro
      cytotoxicity against the P388 murine leukemia cell line with IC(50)'s of 18.8,
      2.7, and 15.6 microg/mL, respectively. Compound 2 showed moderate activity
      against the PANC-1 pancreatic cell line with an IC(50) of 18.7 microg/mL.

PMID- 15730255
TI  - Bisnortriterpenes from Salacia madagascariensis.
AB  - A new bisnortriterpene quinone methide, 20-epi-isoiguesterinol (2), and a new 6
      oxophenolic triterpene, 6-oxoisoiguesterin (5), as well as two known compounds,
      isoiguesterin (1) and isoiguesterinol (4), were isolated from the petroleum ether
      extract of the roots of Salacia madagascariensis. Isoiguesterin (1) and 20-epi
      isoiguesterinol (2) showed potent activity against Leishmania.

PMID- 15730256
TI  - Rhizochalin A, a novel two-headed sphingolipid from the sponge Rhizochalina
      incrustata.
AB  - Rhizochalin A (4), the fourth representative of two-headed glycosphingolipids,
      was isolated as its peracetate from the sponge Rhizochalina incrustata. Its
      structure has been established as the 2-ethyl carbamoate of rhizochalin on the
      basis of spectroscopic data and chemical transformations.

PMID- 15730257
TI  - Communesins G and H, new alkaloids from the psychrotolerant fungus Penicillium
      rivulum.
AB  - Communesins G (1) and H (2), two new alkaloids, have been isolated from the
      psychrotolerant, new species Penicillium rivulum Frisvad. The compounds were
      isolated by high-speed countercurrent chromatography and preparative HPLC using
      UV-guided fractionation. The structures were determined from 1D and 2D NMR
      techniques and HRESIMS. In contrast to all other known communesins, 1 and 2 were
      found inactive in antimicrobial, antiviral, and anticancer assays.

PMID- 15730258
TI  - Poipuol, a new metabolite from a Hawaiian sponge of the genus Hyrtios.
AB  - A new metabolite, poipuol (1), was isolated from an undescribed marine sponge
      Hyrtios sp. collected in Kauai Island, Hawaii. The structure was determined from
      spectroscopic data.

PMID- 15730259
TI  - Steroidal alkaloids from the bulbs of Fritillaria puqiensis.
AB  - Four new steroidal alkaloids, puqienine A (1), puqienine B (2), N
      demethylpuqietinone (3), and puqietinonoside (4), along with a known steroidal
      alkaloid, puqietinone, were isolated from the bulbs of Fritillaria puqiensis. The
      structures of these compounds were elucidated on the basis of spectroscopic
      analysis. The compounds exhibited significant antitussive activity on ammonia
      liquor-induced cough in mice. Furthermore, the compounds were evaluated for
      activities against A549 human lung carcinoma cell line, BGC-823 human stomach
      adenocarcinoma cell line, SMMC-7721 human hepatocarcinoma cell line, and HL-60
      human promyelocytic leukemia cell line.

PMID- 15730260
TI  - Triterpenoid saponins from the roots of Pulsatilla koreana.
AB  - Six new saponins, five lupanes (1-5) and one oleanane (6), along with 11 known
      saponins, were isolated from the roots of Pulsatilla koreana. The structures of
      the new saponins were found to be 23-hydroxy-3beta-[(O-alpha-L-rhamnopyranosyl-(1
      ->2)-O-[O-beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl)oxy]lup-20(29)
      en-28-oic acid (1), 23-hydroxy-3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L
      rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid
      (2), 3beta-[(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-
      >4)]-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (3), 3beta-[(O-beta-D
      glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (4), 23-hydroxy-3beta-[(O-beta-D
      glucopyranosyl-(1-->4)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid
      (5), and hederagenin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-
      >3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (6). Their
      structures were determined on the basis of 1D and 2D NMR ((13)C NMR, (1)H NMR,
      (1)H-(1)H COSY, HMQC, and HMBC) methods, FABMS, and hydrolysis. All isolated
      compounds were evaluated for their cytotoxic activity against A-549 human lung
      carcinoma cells.

PMID- 15730261
TI  - Scalusamides A-C, new pyrrolidine alkaloids from the marine-derived fungus
      Penicillium citrinum.
AB  - Three new pyrrolidine alkaloids, scalusamides A-C (1-3), were isolated from the
      cultured broth of the fungus Penicillium citrinum, which was separated from the
      gastrointestine of a marine fish, and the structures were elucidated by
      spectroscopic data. The absolute stereochemistry of C-2 in the pyrrolidine unit
      was determined by HPLC analysis of a Marfey's derivative of the hydrolysate of 1,
      while that of 2 and 3 was assigned by comparison of spectroscopic data of 3 and
      reductive products of 1 and 2. On the other hand, each of 1-3 was found to be a
      mixture of epimers at C-7. Scalusamide A (1) exhibited antifungal and
      antibacterial activities.

PMID- 15730262
TI  - Additional pyrrolomycins from cultures of Streptomyces fumanus.
AB  - Along with dioxapyrrolomycin (1), four new pyrrolomycin antibiotics, namely,
      pyrrolomycin G (3), pyrrolomycin H (4), pyrrolomycin I (5), and pyrrolomycin J
      (6), were produced in cultures of Streptomyces fumanus. Apart from
      dioxapyrrolomycin, pyrrolomycin G and pyrrolomycin H are the only other chiral
      members of the pyrrolomycin family of antibiotics, and their absolute
      stereochemistry was deduced to be 13S. Here, we report the isolation, structure
      elucidation, and antimicrobial activity of these new pyrrolomycins.

PMID- 15730263
TI  - Mycgranol, a new diterpene from the marine sponge Mycale aff. graveleyi.
AB  - Mycgranol, a new isocopalane diterpene (methyl 1beta-hydroxy-2-oxoisocopalanoate)
      was isolated from the Kenyan sponge Mycale (Aegogropila) aff. graveleyi. The
      structure of the compound was elucidated by interpretation of MS, COSY, HMQC,
      HMBC, and ROESY data. The absolute configuration of mycgranol was determined to
      be the same as that of the nudibranch isocopalane diterpenes rather than that of
      the ent-compounds known from sponges of the genus Spongia.

PMID- 15730264
TI  - Physaloside A, an acylated sucrose ester from Physalis viscosa.
AB  - Chemical investigations of the crude MeOH extract of Physalis viscosa led to the
      identification of the novel acylated sucrose ester physaloside A (1). The
      structure of 1 was determined by 2D NMR analysis, and the absolute configuration
      was determined by chemical degradation and comparison with authentic standards.

PMID- 15730265
TI  - Antioxidative constituents of Etlingera elatior.
AB  - Phytochemical studies on the rhizomes of Etlingera elatior have resulted in the
      isolation of 1,7-bis(4-hydroxyphenyl)-2,4,6-heptatrienone (1), demethoxycurcumin
      (2), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (3), 16-hydroxylabda
      8(17),11,13-trien-15,16-olide (4), stigmast-4-en-3-one, stigmast-4-ene-3,6-dione,
      stigmast-4-en-6beta-ol-3-one, and 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta
      ol. Compounds 1 and 4 are new, and their structures were elucidated by analysis
      of spectroscopic data. Diarylheptanoids 1-3 were found to inhibit lipid
      peroxidation in a more potent manner than alpha-tocopherol.

PMID- 15730266
TI  - Flavonolignans from Avena sativa.
AB  - Three flavonolignans derived from the flavone tricin were isolated from Avena
      sativa herb. This is the first report of the presence of flavonolignans in A.
      sativa. In the known compounds 1a and 1b, a coniferyl alcohol moiety is linked to
      the flavone by an ether bond; in the new natural product 2, it is linked by C-C
      bonds. Structure elucidation of compound 2 was performed by 1D and 2D NMR
      experiments, and the absolute configuration was determined from circular dichroic
      data.

PMID- 15730267
TI  - Biological chemistry of naturally occurring thiols of microbial and marine
      origin.
AB  - The presence of thiols in living systems is critical for the maintenance of
      cellular redox potentials and protein thiol-disulfide ratios, as well as for the
      protection of cells from reactive oxygen species. In addition to the well-studied
      tripeptide glutathione (gamma-Glu-Cys-Gly), a number of compounds have been
      identified that contribute to these essential cellular roles. This review
      provides a survey of the chemistry and biochemistry of several critically
      important and naturally occurring intracellular thiols such as coenzyme M,
      trypanothione, mycothiol, ergothioneine, and the ovothiols. Coenzyme M is a key
      thiol required for methane production in methogenic bacteria. Trypanothione and
      mycothiol are very important to the biochemistry of a number of human pathogens,
      and the enzymes utilizing these thiols have been recognized as important novel
      drug targets. Ergothioneine, although synthesized by fungi and the
      Actinomycetales bacteria, is present at significant physiological levels in
      humans and may contribute to single electron redox reactions in cells. The
      ovothiols appear to function as important modulators of reactive oxygen toxicity
      and appear to serve as small molecule mimics of glutathione peroxidase, a key
      enzyme in the detoxification of reactive oxygen species.

PMID- 15730268
TI  - Anion-binding behavior of hybrid calixpyrroles.
AB  - Hybrid calixpyrrole systems are calixpyrrole-like macrocycles that are based on
      more than one type of small molecule building block. Structurally, these "mixed
      breed" macrocycles differ from calixpyrroles in that some pyrrolic units in the
      latter are replaced by other hetereocyclic units such as furan, thiophene,
      bipyrrole, and bithiophene. Although several such systems have been reported in
      recent years, only a few have been studied as possible anion receptors. In this
      paper, the results of detailed anion binding studies involving several prototypic
      systems are reported. Taken in concert, these results highlight the fact that
      some hybrid systems, including compounds 2-5, display anion affinities that are
      considerably weaker than those of the parent system 1. On the other hand, they
      also show that compounds 6-8 are good receptors for "Y-shaped" anions, such as
      carboxylates, and that they bind these species with high affinity. These findings
      are strongly supported by solid-state structural studies, which reveal an
      interesting "cross binding mode" for the binding of carboxylate anions by the bis
      thiophene, bis-pyrrole system 7.

PMID- 15730269
TI  - Oligomeric ligands incorporating multiple 5,5'-diethynyl-2,2'-bipyridine moieties
      bridged and end-capped by 3,4-dibutylthiophene units.
AB  - In this work, we detail the synthesis and photophysical properties of a series of
      soluble polybipyridine ligands comprising one to five bipyridine units sandwiched
      between rigid carbon-carbon triple bonds substituted by 3,4-dibutylthiophene
      repeating units. The dual Sonogashira coupling reaction of 5,5'-dibromo-2,2'
      bipyridine with TMS- and (CH3)2C(OH)-protected acetylene allows the synthesis of
      a dissymmetrically functionalized building block which was selectively
      deprotected at either the TMS or 2-hydroxyprop-2-yl site. Various combinations
      allow the interconnection of the terminal alkyne to 3,4-dibutyl-2,5
      diiodothiophene or 3,4-dibutyl-2-iodothiophene leading to bipyridine frameworks
      bearing two acetylene-protected groups or one acetylenethiophene/one acetylene
      protected function. It is possible therefore to construct dimeric to pentameric
      bipyridine ligands where the chelating subunit is bridged by a 3,4-dibutyl-2,5
      diethynylthiophene spacer and end-capped by a 3,4-dibutyl-2-ethynylthiophene
      stopper. All cross-coupling reactions are promoted with palladium(0)
      tetrakistriphenylphosphine under mild conditions. Spectroscopic data for the new
      oligomers are discussed in terms of the extent of pi-electron conjugation. Upon
      increasing the number of pi-electrons from 24 to 104, there is a progressive
      lowering in the energy of absorption and fluorescence transitions, while the
      emission quantum yields remain essentially constant. The LUMO levels of these
      large molecules, estimated by cyclic voltammetry, lie in the range -3.06 to -3.18
      eV.

PMID- 15730270
TI  - Experimental and computational studies of ring inversion of 1,4-benzodiazepin-2
      ones: implications for memory of chirality transformations.
AB  - We recently reported the enantioselective syntheses of quaternary 1,4
      benzodiazepin-2-ones via memory of chirality. The success of this method depends
      on formation of conformationally chiral enolates that racemize very slowly under
      the reaction conditions. As a prelude to undertaking experimental and
      computational studies on the racemization of these enolates, we have studied the
      ring-inversion process of the parent 1,4-benzodiazepin-2-ones. In this paper, we
      use dynamic and 2D-EXSY NMR to characterize inversion barriers. Using DFT
      calculations, we reproduce the experimental results with high accuracy (within 1
      2 kcal/mol). Structural parameters obtained from DFT calculations provide
      valuable insights into the important effect of the N1 substituent on the ring
      inversion barrier and shed light on the mechanism of the memory of chirality
      method. These measurements and calculations provide a foundation for future
      studies of benzodiazepine enolates and will be valuable in the design of new
      memory of chirality reactions.

PMID- 15730271
TI  - 8-endo versus 7-exo cyclization of alpha-carbamoyl radicals. A combination of
      experimental and theoretical studies.
AB  - Atom transfer radical cyclization reactions of N-(4-pentenyl)iodoacetamides were
      investigated. The reactions were efficiently promoted by BF3.OEt2. For N-alkenyl
      substituted iodoamides, excellent regioselectivity in favor of 8-endo cyclization
      was observed, while both 7-exo and 8-endo cyclization products were formed with
      the 8-endo cyclization preferred in the cases of N-(2-allylphenyl)-substituted
      iodoamides. Density functional theory calculations at the B3LYP/6-31G level
      revealed that both the s-trans and the s-cis conformational transition structures
      were feasible for the 8-endo cyclization of N-alkenyl-substituted alpha-carbamoyl
      radicals while 7-exo transition structures were much less stable. For the
      cyclization of N-(2-allylphenyl)-substituted alpha-carbamoyl radicals, the
      transition structures for 8-endo and 7-exo cyclizations were of comparable
      energy. These results were in excellent agreement with the experimental
      observations.

PMID- 15730272
TI  - Conformation analyses, dynamic behavior and amide bond distortions of medium
      sized heterocycles. 1. Partially and fully reduced 1-benzazepines.
AB  - Five 1-benzazepine heterocycles were synthesized by utilizing transition-metal
      catalyzed processes in key bond-forming steps. exo-Methylene and methyl
      substituents were introduced at position 5, as well as a unit of unsaturation
      between positions 3 and 4, with benzoyl or benzyl N-substituents. Solution- and
      solid-state structures were examined, using dynamic NMR spectroscopy and X-ray
      crystallography, corroborated by molecular mechanics calculations. Greater amide
      distortion is associated with a more stable ground-state structure, which is in
      turn more reluctant to undergo conformational changes.

PMID- 15730274
TI  - Noncovalent encapsulation of cobaltocenium inside resorcinarene molecular
      capsules.
AB  - The encapsulation of cobaltocenium (Cob+) inside hexameric molecular capsules of
      two different resorcinarenes was investigated in dichloromethane solution. Both
      1H NMR spectroscopic and voltammetric experiments clearly reveal that Cob+
      experiences encapsulation. Diffusion coefficient measurements obtained from PGSE
      NMR experiments indicate that the molecular capsules exist in dichloromethane
      solution in the absence of any cations. Bound and free Cob+ ions undergo slow
      exchange on the NMR time scale, but the bound Cob+ ions rotate and/or tumble
      freely inside the molecular capsules. Under experimental conditions suitable for
      voltammetry the encapsulation of Cob+ depends on the nature of the supporting
      electrolyte. Tetraalkylammonium hexafluorophosphate, tetrafluoroborate, and
      perchlorate supporting electrolytes prevent the encapsulation of Cob+, while
      tetraalkylammonium chloride and bromide salts allow it. The nature of the
      tetraalkylammonium cation plays a smaller role in the encapsulation. Finally, the
      structure of the resorcinarene also factors into the overall stability of the
      molecular assembly.

PMID- 15730273
TI  - Conformation analyses, dynamic behavior, and amide bond distortions of medium
      sized heterocycles. 2. Partially and fully reduced 1-benzazocines, benzazonines,
      and benzazecines.
AB  - Partially and fully reduced forms of benzo-fused eight- to ten-membered nitrogen
      heterocycles (1-benzazecines, 1-benzazonines and 1-benzazecines) have been
      prepared. Conformational features, transannular distances and dynamic behavior
      were studied using X-ray crystallography and VT NMR spectroscopy. The amide
      moiety in the nine-membered benzazonine ring 5b favors N-pyramidization, whereas
      the ten-membered benzazecine 5c adopts an amide twist. Molecular mechanics
      calculations reveals a correlation between the amide twist (tau) and ring
      stability. The dynamic behavior of the heterocycles in solution were also found
      to be dependent on the extent and nature of the amide distortion. We thus
      conclude that ring strain of these medium-sized heterocyclic rings is relieved
      through amide distortion, which leads to a more stable structure.

PMID- 15730275
TI  - Theoretical study of the addition patterns of C60 fluorination: C60Fn (n = 1-60).
AB  - A systematic study is presented of addition patterns occurring upon fluorination
      of C60. We use the program SACHA, which increments the number of fluorine
      addends, tests all available addition sites within a given cutoff radius, and
      selects the most energetically stable structure for further addition on the basis
      of full AM1 optimizations for every isomer. The lowest energy structures are
      optimized at HF/3-21G level of theory. A number of distinct addition routes are
      predicted, based on octahedral, 'S', and 'T' addition patterns, leading both to
      experimentally observed C60F(n) isomers and to isomers not previously described
      in the literature. Furthermore the main addition routes were analyzed for C60F2n
      isomers, using ab initio global and local aromaticity calculations. For this,
      magnetizability and NICS calculations have been carried out at HF/3-21G level of
      theory. We show the possibility of using NICS to predict the next preferential
      addition site, matching the above-described addition routes.

PMID- 15730276
TI  - Stereoselective synthesis of conformationally constrained 2'-deoxy-4'-thia beta
      anomeric spirocyclic nucleosides featuring either hydroxyl configuration at C5'.
AB  - An enantioselective approach to 2'-deoxy-4'-thia spirocyclic nucleosides
      featuring an alpha- or beta-hydroxyl substituent at C-5' of the carbocyclic ring
      is detailed. The starting point is the mandelate acetal 8. The overall strategy
      involves the stereocontrolled dihydroxylation of this dihydrothiophene,
      subsequent generation of the keto acetonide 12 followed by its Meerwein-Ponndorf
      Verley reduction and beta-elimination, protection of the resulting dihydroxy
      thiaglycal, electrophilic glycosidation according to the Haraguchi protocol,
      reductive removal of the phenylseleno group, and end-game global deprotection.
      Acquisition of the alpha- and beta-5'-isomers is equally facile. Various 1D and
      2D NMR techniques are used for assigning configuration.

PMID- 15730277
TI  - Practical synthesis of enantiopure spiro[4.4]nonane C-(2'-deoxy)ribonucleosides.
AB  - The levorotatory diol 7 has been sequentially monosilylated, dehydrated, and
      oxidized at the allylic methylene group to provide (+)-12. The enantiomeric
      dextrorotatory diol 7 has been directed down a different sequence of steps
      involving monosilylation, dehydration, hydroboration, Swern oxidation, and
      regioselective introduction of a conjugated double bond to generate (-)-33. The
      novel feature of these transformations is that two key deoxycarbospironucleoside
      intermediates of the proper absolute configuration have been made available from
      enantiomerically related precursors. Also reported is a highly practical and
      reliable means for the formation of novel 2'-deoxyribonucleosides of novel
      structural type from these spirocyclic cyclopentenones.

PMID- 15730278
TI  - Regio- and stereoselective ring opening of 2,3-diaryl oxiranes by LiBr/Amberlyst
      15: a new stereocontrolled access to 1,2-diaryl-2-bromo alcohols.
AB  - Both symmetrical and nonsymmetrical trans-2,3-diaryloxiranes are regio- and
      stereoselectively opened by the LiBr/Amberlyst 15 system. In the case of
      symmetrical trans-stilbene oxide, the syn- versus anti-bromohydrins ratio ranged
      between 88/12 and 30/70, by varying the reaction temperature from 20 to -30
      degrees C. In the case of nonsymmetrical para-substituted trans-2,3
      diaryloxiranes, the regioselectivity is determined by electronic effects. If one
      phenyl bears a strong electron-withdrawing group (as NO2 or CF3), the
      nucleophilic attack is totally on the beta-carbon with respect to the substituted
      phenyl ring. With one phenyl bearing a strong electron-releasing group (OCH3),
      the regioselectivity is reversed. Ab initio calculation at the DFT/B3LYP/6-31G
      level, run on protonated epoxide structures, supports the formation of a cationic
      acyclic intermediate. Application of the method on ortho-methoxy and ortho-nitro
      2,3-diaryloxiranes afforded the syn-bromohydrins in excellent yield, via regio-
      and stereoselective opening at either alpha- or beta-carbon, respectively.

PMID- 15730279
TI  - "Molecular chameleons". Design and synthesis of a second series of flexible
      nucleosides.
AB  - The second series of flexible shape-modified nucleosides is introduced. The
      "fleximers" feature the purine ring systems split into their individual imidazole
      and pyrimidine components. This structural modification serves to introduce
      flexibility to the nucleoside while still retaining the elements essential for
      recognition. As a consequence, these structurally innovative nucleosides can more
      readily adapt to their environment and should find use as bioprobes for
      investigating enzyme-coenzyme binding sites as well as nucleic acid and protein
      interactions. Their design and synthesis is described.

PMID- 15730280
TI  - Constrained nucleic acids (CNA). Part 2. Synthesis of conformationally restricted
      dinucleotide units featuring noncanonical alpha/beta/gamma or delta/epsilon/zeta
      torsion angle combinations.
AB  - Four dinucleotide building units of nucleic acids in which three out of six
      backbone torsion angles are included in a dioxaphosphorinane ring structure (D
      CNA family) have been synthesized: two diastereoisomeric alpha,beta,gamma-D-CNA
      {cis and trans} and two diastereoisomeric delta,epsilon,zeta-D-CNA {(S(C4'),R(P))
      and (S(C4'),S(P))}. The structural analysis of these conformationally restricted
      dinucleotides, using NMR spectroscopy and X-ray crystallography, shows that these
      D-CNA structural elements allow the stabilization of torsion angle combinations,
      alpha/beta/gamma and delta/epsilon/zeta, that are significantly different from
      those typically observed in canonical A- or B-form duplexes.

PMID- 15730281
TI  - Dichlorocarbene addition to cyclopropenes: a computational study.
AB  - Reaction paths for addition of dichlorocarbene to 1,2-disubstituted cyclopropenes
      were calculated using hybrid density functional theory (B3LYP/6-31G) in the gas
      phase and in the presence of a continuum solvation model corresponding to
      acetonitrile. In both the gas phase and acetonitrile, :CCl2-cyclopropene addition
      follows an asymmetric, non-least-motion approach. Barriers to addition range from
      0 to 2 kcal/mol. The reactions proceed in concerted fashion in both the gas phase
      and solution to yield 1,3-dienes or bicyclobutanes. The reaction pathway on this
      complex potential energy surface of this reaction appears to bifurcate, and the
      product distribution is believed to be controlled by reaction dynamics. At the
      present level of theory, there appears to be no minimum on the potential energy
      surface corresponding to a dipolar intermediate.

PMID- 15730282
TI  - Synthesis, reaction, and recycle of light fluorous Grubbs-Hoveyda catalysts for
      alkene metathesis.
AB  - Light fluorous versions of first- and second-generation Grubbs-Hoveyda metathesis
      catalysts are introduced. These exhibit the expected reactivity profile, are
      readily recovered from reaction mixtures by fluorous solid-phase extraction, and
      can be routinely reused five or more times. The catalysts can be used in a stand
      alone fashion, or supported on fluorous silica gel.

PMID- 15730283
TI  - Kinetics and mechanism of hydration of o-thioquinone methide in aqueous solution.
      Rate-determining protonation of sulfur.
AB  - o-Thioquinone methide, 2, was generated in aqueous solution by flash photolysis
      of benzothiete, 1, and rates of hydration of this quinone methide to o
      mercaptobenzyl alcohol, 3, were measured in perchloric acid solutions, using H2O
      and D2O as the solvent, and also in acetic acid and
      tris(hydroxymethyl)methylammonium ion buffers, using H2O as the solvent. The rate
      profiles constructed from these data show hydronium-ion-catalyzed and uncatalyzed
      hydration reaction regions, just like the rate profiles based on literature data
      for hydration of the oxygen analogue, o-quinone methide, of the presently
      examined substrate. Solvent isotope effects on hydronium-ion catalysis of
      hydration for the two substrates, however, are quite different: k(H)/k(D) = 0.42
      for the oxygen quinone methide, whereas k(H)/k(D) = 1.66 for the sulfur
      substrate. The inverse nature (k(H)/k(D) < 1) of the isotope effect in the oxygen
      system indicates that this reaction occurs by a preequilibrium proton-transfer
      reaction mechanism, with protonation of the substrate on its oxygen atom being
      fast and reversible and capture of the benzyl-type carbocationic intermediate so
      formed being rate-determining. The normal direction (k(H)/k(D) > 1) of the
      isotope effect in the sulfur system, on the other hand, suggests that protonation
      of the substrate on its sulfur atom is in this case rate-determining, with
      carbocation capture a fast following step. A semiquantitative argument supporting
      this hypothesis is presented.

PMID- 15730285
TI  - Total synthesis of sordaricin.
AB  - An enantioconvergent total synthesis of sordaricin (3), the diterpene aglycon of
      an important class of antifungal compounds, is described. Two approaches were
      explored, the first of which utilized a possible biogenetic intramolecular [4 +
      2] cycloaddition to form the complete carbon skeleton of the target molecule as a
      single regioisomer 30. A second approach employed a tandem
      cycloreversion/intramolecular [4 + 2] cycloaddition process to afford not only
      the desired product 30 but also significant quantities of the undesired
      regioisomer iso-30. An investigation into the reasons for the difference in
      regioselectivity between these two reactions revealed the intervention of a
      cycloreversion/cycloaddition pathway at elevated temperatures leading to the
      formation of iso-30. Experimental evidence supports the hypothesis that iso-30 is
      the more thermodynamically stable of the two regioisomers.

PMID- 15730284
TI  - Solvent polarity and organic reactivity in mixed solvents: evidence using a
      reactive molecular probe to assess the role of preferential solvation in aqueous
      alcohols.
AB  - Product selectivities [S = ([ester product]/[acid product]) x ([water]/[alcohol
      solvent])] are reported for solvolyses of p-methoxybenzoyl chloride (2) in
      aqueous methanol, ethanol, 2,2,2-trifluoroethanol, n-propyl alcohol, isopropyl
      alcohol, and tert-butyl alcohol at 25, 35, and 45 degrees C. S values are small
      and depend significantly on the alcohol cosolvent, varying from 1.3 in methanol
      to 0.1 in tert-butyl alcohol, but S depends only slightly on the solvent
      composition, and on the temperature. As S adjusts the product ratios for changes
      in bulk solvent compositions, it is suggested that preferential solvation by
      either alcohol or water at the reaction site is not a major factor influencing
      rates or products. Logarithms of rates of solvolyses of 2 correlate well with
      Kosower Z values (based on solvatochromism). In contrast, another solvatochromic
      polarity index, E(T)(30), shows "dispersion" in correlations with the solvent
      ionizing power parameter, Y(OTs), probably due to aromatic ring and other
      solvation effects.

PMID- 15730286
TI  - Structures and stabilities of diacetylene-expanded polyhedranes by quantum
      mechanics and molecular mechanics.
AB  - The structures, heats of formation, and strain energies of diacetylene (buta-1,3
      diynediyl) expanded molecules have been computed with ab initio and molecular
      mechanics calculations. Expanded cubane, prismane, tetrahedrane, and expanded
      monocyclics and bicyclics were optimized at the HF/6-31G(d) and B3LYP/6-31G(d)
      levels. The heats of formation of these systems were obtained from isodesmic
      equations at the HF/6-31G(d) level. Heats of formation were also calculated from
      Benson group equivalents. The strain energies of these expanded molecules were
      estimated by several independent methods. An adapted MM3 molecular mechanics
      force field, specifically parametrized to treat conjugated acetylene units, was
      employed for one measure of strain energy and as an additional method for
      structural analysis. Expanded dodecahedrane and icosahedrane were calculated by
      this method. Expanded molecules were considered structurally in the context of
      their potential material applications.

PMID- 15730287
TI  - Synthesis and highly enantioselective hydrogenation of exocyclic enamides: (Z)-3
      arylidene-4-acetyl-3,4-dihydro-2H- 1,4-benzoxazines.
AB  - Highly enantioselective hydrogenation of exocyclic enamides, (Z)-3-arylidene-4
      acyl-3,4-dihydro-2H-benzoxazines, was achieved in up to 98.6% ee by using
      Rh/(R,R)-Me-Duphos complex as the catalytic system. The absolute configuration of
      the product was assigned as R by chemical interrelations.

PMID- 15730288
TI  - 5-Exo versus 6-endo cyclization of nucleoside 2-sila-5-hexenyl radicals: reaction
      of 6-(bromomethyl)dimethylsilyl 1',2'-unsaturated uridines.
AB  - The mode of cyclization of 2-sila-5-hexen-1-yl radicals generated from 6
      (bromomethyl)dimethylsilyl-1',2'-unsaturated uridines was investigated. In
      contrast to the case of the 2'-unsubstituted 6-silicon-tethered substrate (4),
      which undergoes exclusive 6-endo-cyclization, reactions of the 2'-substituted
      (Me, CO2Me, OBz, and Cl) derivatives (14, 20, 22, and 24) uniformly proceeded in
      preferential or exclusive 5-exo-mode. The Tamao oxidation of the resulting
      cyclized products was also carried out to synthesize the corresponding 1'-C
      hydroxymethyl derivatives.

PMID- 15730289
TI  - Synthesis of proteophosphoglycans of Leishmania major and Leishmania mexicana.
AB  - A novel approach for the synthesis of various fragments of proteophosphoglycans
      from Leishmania major and Leishmania mexicana proteophosphoglycans has been
      developed. These compounds have been obtained by coupling alpha-mannosyl and
      alpha-N-acetyl-glucosamine phosphoramidite derivatives with the serine hydroxyl
      of various amino acids and peptides to give, after oxidation with tert-BuOOH,
      phosphotriesters exclusively as alpha-anomers in good yield. The resulting
      compounds could be deblocked using conventional methods. Glycophosphorylation of
      preassembled and properly protected peptides was found to be more efficient for
      the preparation of proteophosphoglycan fragments than a building block approach
      strategy using a phosphoglycosylserine derivative.

PMID- 15730290
TI  - Synthesis and complexing properties of [2.n](2,6)pyridinocrownophanes.
AB  - [2.n](2,6)Pyridinocrownophanes (3a-e) were efficiently prepared by intramolecular
      [2 + 2] photocycloaddition of vinylpyridine derivatives under irradiation using a
      400-W high-pressure mercury lamp through a Pyrex filter. They were of cis
      configuration with respect to the cyclobutane ring, which was proven by the
      specific methine proton NMR resonances at delta 3.98-4.08. From ESI-MS analysis
      3a-e were found to form 1:1 complexes with Ag+ cation. In a liquid-liquid
      extraction, 3 showed the highest affinity toward Ag+ cation among several heavy
      metal nitrates. In this series, 3c possessing four ethereal oxygen atoms was
      found to show the highest Ag+ affinity, according to the liquid-liquid extraction
      and determination of stability constant with the cation. The photoreactivity of
      precursor vinylpyridines is discussed by the predictor gamma(r(c)) proposed by
      Caldwell.

PMID- 15730291
TI  - Oxime-based salen-type tetradentate ligands with high stability against imine
      metathesis reaction.
AB  - Although salen and its analogues are versatile chelate ligands in inorganic and
      organometallic chemistry, synthesis of unsymmetrical salen derivatives consisting
      of two different salicylideneimine moieties is difficult because of the C=N bond
      recombination. To develop stable analogues of salen-type ligands, we synthesized
      a series of new ligands salamo (=1,2-bis(salicylideneaminooxy)ethane) on the
      basis of O-alkyl oxime instead of the imine moiety. Eight salamo ligands 1a-h
      were prepared in 64-88% yields as colorless crystals from the corresponding
      salicylaldehydes 2a-h. The crystal structure of 1a-c suggests that the oxime-OH
      form is more predominant than the keto-NH form. The reaction of 2a-e with excess
      1,2-bis(aminooxy)ethane gave monooximes 3a-e in 59-86%, which further reacted
      with a different salicylaldehyde to afford unsymmetrical salamo ligands 4-8 as
      stable crystals in 51-70%. No reaction took place when a mixture of salamo
      derivatives 1a and 1b was treated at 40 degrees C in H2O/MeCN (5:95). However,
      the metathesis reaction of salen derivatives 9a and 9b completed in 2 h to give a
      statistical mixture. Monooxime 3b was much more stable than monoimine 11 which is
      difficult to be isolated. These results indicate the extremely high stability of
      the salamo derivatives 1 and precursors 3.

PMID- 15730292
TI  - Palladium-catalyzed tandem cyclization/Suzuki coupling of 1,6-enynes: reaction
      scope and mechanism.
AB  - A palldium(0)-catalyzed tandem cyclization/Suzuki coupling reaction of various
      1,6-enyne substrates was developed. This Pd-catalyzed enyne cyclization reaction
      represents a new process for the synthesis of stereodefined alpha-arylmethylene
      gamma-butyrolactones, lactams, multifunctional tetrahydrofurans, pyrrolidines,
      and cyclopentanes. The mechanism of the reaction was studied by the employment of
      different enyne isomers and boronic acids; a pi-allyl palladium intermediate was
      suggested to explain the formation of the cyclic products. The stereochemistry of
      this reaction can be well explained by a chairlike transition state.

PMID- 15730293
TI  - A fast radical chain mechanism in the polyfluoroalkoxylation of aromatics through
      NO2 group displacement. Mechanistic and theoretical studies.
AB  - Introduction of polyfluoroalkoxy and polyfluoroalkylthio substituents in aromatic
      rings can be achieved with mild conditions and short times thorough reaction of
      concentrated solutions of dinitrobenzenes in DMF with polyfluoro alcohols and
      polyfluoro thiols in moderate excess, in the presence of excess
      tetrabutylammonium fluoride as a base. Mechanistic studies suggest that under
      these conditions a fast radical chain mechanism operates. This mechanism is
      elicited by oxidation of a Meisenheimer complex and proceeds through a radical
      aromatic substitution with the polyfluoroalkoxy or the polyfluoroalkylthio
      radicals as key intermediates. At low concentrations, entrainment can be achieved
      with superoxide anion. A rationale for this effect is discussed. Answers to
      particular questions about the proposed mechanism are achieved through a
      theoretical study at the B3LYP/6-31+G(d,p) level. Specifically, the competition
      between the radical mechanism and the corresponding polar one (classical S(N)Ar
      reaction) is studied in that way, with the conclusion that the key steps of the
      radical mechanism in our reaction conditions (polar aprotic solvent) are at least
      as efficient as the ones of the polar one, thus justifying the observed kinetic
      advantage for the chain reaction in the conditions where an efficient initiation
      occurs.

PMID- 15730294
TI  - Enantioreversal in the sharpless asymmetric epoxidation reaction controlled by
      the molecular weight of a covalently appended achiral polymer.
AB  - Polymers such as poly(ethylene glycol) (PEG) have proven use in a variety of
      applications including organic synthesis. We now disclose our investigations into
      the recently disputed report that PEG tartrate esters can reverse the
      enantioselectivity of the Sharpless asymmetric epoxidation reaction. The results
      presented herein have clarified that the enantioselectivity of this reaction can
      be reproducibly reversed solely as a function of the molecular weight of the
      appended PEG. By preparing a range of tartrate ligands with varying PEG chains
      lengths, the reversal was found to occur within a molecular weight change of only
      800. As the PEG chain did not affect the inherent chirality of the ligand, the
      enantioreversal was proposed to occur as a result of two Ti-ligand complexes
      which differ in their molecularity of ligand, one monomeric in ligand and the
      other dimeric. Support for this hypothesis was given through equilibrium
      measurements which revealed that the predominant species in Ti/PEG tartrate ester
      mixtures is a distinct 2:1 Ti-ligand complex, as opposed to the 2:2 Ti-ligand
      complex of traditional Sharpless asymmetric epoxidations. In total, these data
      represent an unrecognized property of PEG-supported catalysts that could open up
      new venues in the control of asymmetric reactions by means of achiral appended
      polymers.

PMID- 15730295
TI  - Urea host monomers for stoichiometric molecular imprinting of oxyanions.
AB  - A series of urea-based vinyl monomers was synthesized and investigated for their
      ability to function as polymerizable hosts for the molecular imprinting of N-Z-D-
      or L-glutamic acid in polar media (DMSO or DMF). The monomers were synthesized in
      one step from a polymerizable isocyanate and a nonpolymerizable amine or vice
      versa, with yields typically over 70%. Prior to polymerization their solution
      binding properties vis-a-vis tetrabutylammonium benzoate in DMSO were
      investigated by 1H NMR, UV-vis and fluorescence monitored titrations. The
      affinities of the urea monomers for benzoate depended upon the substitution
      pattern of the urea, with all diaryl ureas exhibiting high affinity. EDMA-based
      imprinted polymers prepared in DMF or DMSO against Z-D-(or L)-glutamic acid using
      2 equiv of the urea monomer and 2 equiv of base were able to recognize the
      imprinted dianion as well as larger molecules containing the glutamic acid
      substructure. The affinity, reflected in liquid chromatography retention data,
      correlated with the solution binding properties of the corresponding monomers.

PMID- 15730296
TI  - Multiple isotope effect study of the acid-catalyzed hydrolysis of methyl formate.
AB  - Multiple isotope effects have been measured for the acid-catalyzed hydrolysis of
      methyl formate in 0.5 M HCl at 20 degrees C. The isotope effects in the present
      investigation include the carbonyl carbon (13k = 1.028 +/- 0.001), the carbonyl
      oxygen (18k = 0.9945 +/- 0.0009), the nucleophile oxygen (18k = 0.995 +/- 0.001),
      and the formyl hydrogen ((D)k = 0.81 +/- 0.02). Determination of the carbonyl
      carbon, carbonyl oxygen, and formyl hydrogen isotope effects was performed via
      isotopic analysis of residual substrate. However, determination of the oxygen
      nucleophile isotope effect required analysis of the oxygen atoms of the product
      (formic acid), which exchange with the solvent (water) under acid conditions.
      This necessitated measurement of the rate of exchange of these oxygen atoms under
      the conditions for hydrolysis (k(ex) = 0.0723 min(-1)) and correction of the raw
      isotope ratios measured during the nucleophile-O isotope effect experiment. These
      results, along with the previously reported isotope effect for the leaving oxygen
      (18k = 1.0009) and the ratio of the rate of hydrolysis to that of exchange of the
      carbonyl oxygen with water (k(h)/k(ex) = 11.3), give a detailed picture of the
      transition-state structure for the reaction.

PMID- 15730297
TI  - Heterocyclic alpha-alkylidene cyclopentenones obtained via a Pauson-Khand
      reaction of amino acid derived allenynes. A scope and limitation study directed
      toward the preparation of a tricyclic pyrrole library.
AB  - The synthesis of a novel class of tricyclic pyrroles has been accomplished by
      using a Pauson-Khand/Stetter/Paal-Knorr reaction sequence. Full details of the
      Pauson-Khand reaction of amino acid tethered allenynes 4a-e and 9a-d are
      disclosed. The study of this reaction led to the discovery of an unprecedented
      substituent effect on the diastereoselectivity of the Mo(CO)6 mediated allenic
      Pauson-Khand reaction. It was found that amino acid tethered allenynes with
      aromatic side chains afford alpha-alkylidene cyclopentenones with the opposite
      diastereoselectivity compared to those with aliphatic side chains. This effect
      has been attributed to complexation of the metal mediator to the aromatic ring in
      the substrate. Furthermore, an isomerization of one of the diastereomers of the
      alpha-alkylidene cyclopentenones was encountered, leading to eventual
      decomposition. The stable diastereomers were found to react well in the Stetter
      reaction leading to 1,4-diketones that were converted to pyrroles. The
      observation that the first generation of 2-alkyl-substituted pyrroles was
      unstable led to a second generation of 2-carboxamide pyrroles with sufficient
      stability for biological tests which are in progress.

PMID- 15730298
TI  - Relationships between the electrophilicity index and experimental rate
      coefficients for the aminolysis of thiolcarbonates and dithiocarbonates.
AB  - Quantitative relationships are reported between the global electrophilicity index
      and the experimental rate coefficients for the reactions of thiolcarbonates and
      dithiocarbonates with piperidine. The validated scale of electrophilicity is then
      used to rationalize the reaction mechanisms of these systems. This scale also
      makes it possible to predict both rate coefficients and Hammett substituent
      constants for a series of systems that have not been experimentally evaluated to
      date.

PMID- 15730299
TI  - Synthesis of 2,3-dihydro-3-hydroxy-2-hydroxylalkylbenzofurans from epoxy
      aldehydes. One-step syntheses of brosimacutin G, vaginidiol, vaginol, smyrindiol,
      xanthoarnol, and Avicenol A. Biomimetic syntheses of angelicin and psoralen.
AB  - We have developed two practical one-step syntheses of 2,3-dihydro-3-hydroxy-2
      hydroxyalkylbenzofurans from readily available optically pure alpha,beta-epoxy
      aldehydes. Electron-deficient resorcinols react with epoxy aldehydes using either
      Cs2CO3 in DMF or KOH/CaCl2 in MeOH to give adducts 13, 16, 18, 20, 21, and
      brosimacutin G (6t). Grignard reagents prepared by low-temperature halogen-metal
      exchange of acetoxy iodocoumarins 35d and 40 and acetoxy bromonaphthalene 41 add
      to epoxy aldehyde (S)-26 to complete the first syntheses of vaginidiol (7c),
      vaginol (7t), smyrindiol (8c), xanthoarnol (8t), and avicenol A (9t). Acid
      catalyzed fragmentation of vaginidiol or vaginol provides angelicin, while that
      of smyrindiol or xanthoarnol affords psoralen. In both cases, the trans isomers
      fragment only twice as fast as the cis isomers, possibly through the intermediacy
      of a common benzylic cation. This may have implications for the biosynthesis of
      angelicin and psoralen.

PMID- 15730300
TI  - Practical asymmetric synthesis of a non-peptidic alphavbeta3 antagonist.
AB  - The development of a practical and highly convergent synthesis of an
      alpha(v)beta3 antagonist is described. The two key fragments present in this
      compound, a tetrahydropyrido[2,3-b]azepine ring system and a chiral 3-aryl-5
      oxopentanoic acid, were constructed independently and then coupled at a late
      stage using a Wittig reaction. The pyridoazepine moiety was prepared from N-Boc 6
      chloro-2-aminopyridine via directed ortho-metalation/alkylation followed by in
      situ cyclization. A Suzuki reaction was then used to attach the propionaldehyde
      side-chain required for Wittig coupling. The coupling partner was prepared from
      asymmetric methanolysis of a 3-substituted glutaric anhydride followed by
      elaboration of the acid moiety to the requisite beta-keto phosphorane. Using this
      route, kilogram quantities of the desired drug candidate were prepared.

PMID- 15730301
TI  - A novel and highly regioselective approach to 5-methoxy-6-substituted-3-sulfonyl
      delta-enlactams from 5-methoxy-3-sulfonyl glutarimide: synthesis of cis-2
      substituted-3-piperidinols.
AB  - A convenient method for the preparation of 5-methoxy-6-substituted-3-sulfonyl
      delta-enlactams via regioselective nucleophilic addition to 5-methoxy-3-sulfonyl
      glutarimide is described. Formal syntheses of L-733,060, CP-99,994, and cassine
      are also reported.

PMID- 15730302
TI  - Microwave-promoted Heck coupling using ultralow metal catalyst concentrations.
AB  - We show that Heck couplings can be performed in water using microwave heating and
      Pd catalyst concentrations as low as 500 ppb. The methodology is simple; all that
      is required as the catalyst is a stock solution of palladium.

PMID- 15730303
TI  - Novel approach to 5-substituted proline derivatives using a silver-catalyzed
      cyclization as the key step.
AB  - A novel synthetic approach to the synthesis of enantiomerically pure 2,5
      disubstituted pyrrolines is described. The methodology involves a Ag-catalyzed 5
      endo-dig cyclization of enantiopure aryl-substituted acetylene-containing amino
      acids. It has also been shown that the obtained pyrrolines can be efficiently
      transformed into the corresponding saturated 5-aryl-substituted proline
      derivatives.

PMID- 15730304
TI  - Remote stereocontrol by sulfinyl groups: reduction of delta-ketosulfoxides.
AB  - The reduction of delta-ketosulfoxides constitutes the first evidence of the
      efficiency of the sulfinyl group to control the stereoselectivity of 1,5
      asymmetric induction processes. The use of DIBAL/Yb(OTf)3 or L-Selectride as the
      reducing agents provides delta-hydroxysulfoxides with the opposite configuration
      at the hydroxylic carbon in a highly stereoselective way.

PMID- 15730305
TI  - Highly stereoselective palladium-catalyzed dithiocarbonylation of propargylic
      mesylates with thiols and carbon monoxide.
AB  - Highly stereoselective dithiocarbonylation of propargylic mesylates with thiols
      and carbon monoxide has been developed by the use of
      tetrakis(triphenylphosphine)palladium(0) as the catalyst at 90 degrees C in THF.
      The reaction affords the corresponding dithioesters in good to excellent yields.
      For some secondary and tertiary propargylic alcohols with a terminal or internal
      triple bond, the reaction stereoselectively produces E-dithioesters as products.
      The dithiocarbonylation is believed to proceed via allenylpalladium and allenyl
      ester intermediates, and the high stereoselectivity might be rationalized by a
      mechanism where nucleophilic attack of a Pd(0)L(n) species on the allenyl sp
      carbon occurs from the less hindered side of an alkyl substituent.

PMID- 15730306
TI  - Novel cuticular hydrocarbons from the cane beetle Antitrogus parvulus-
      4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes-unprecedented anti-anti
      anti-stereochemistry in the 4,6,8,10-methyltetrad.
AB  - The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus
      are 4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes, 1 and 2,
      respectively. Stereoisomers of 2,4,6,8-tetramethylundecanal of established
      relative stereochemistry were derived from 2,4,6-trimethylphenol and were then
      coupled with appropriate methyl-substituted phosphoranes 62 and 25 to furnish
      alkenes, which on reduction provided diastereomers of 1 and 2, respectively.
      Capillary gas chromatography, mass spectrometry, and high resolution 13C NMR
      spectroscopy confirmed 1 as either 84a or 84b and 2 as either 15a or 15b. The
      novelty of these structures and their relative stereochemistry is briefly related
      to polyketide assembly.

PMID- 15730307
TI  - Concise syntheses of the cruciferous phytoalexins brassilexin, sinalexin,
      wasalexins, and analogues: expanding the scope of the vilsmeier formylation.
AB  - Efficient syntheses of the phytoalexins brassilexin, sinalexin, and analogues are
      demonstrated through the application of the Vilsmeier formylation to indoline-2
      thiones followed by a new aqueous ammonia workup procedure. Similarly, a very
      concise two-pot synthesis of the phytoalexins wasalexins using sequential
      formylation-amination of indolin-2-ones is described. Remarkably, this novel
      aqueous ammonia workup allows the sequential one-pot formylation-amination,
      expanding substantially the scope of the Vilsmeier formylation of both indoline-2
      thiones and indolin-2-ones. The examination of the formylation-amination reaction
      and optimization of conditions, as well as the syntheses and antifungal
      activities of several brassilexin analogues, are reported.

PMID- 15730308
TI  - Cholesterol-armed cyclens for helical metal complexes offering chiral self
      aggregation and sensing of amino acid anions in aqueous solutions.
AB  - Cholesterol-armed cyclens worked as octadentate receptors for Na+, Ca2+, and Y3+
      complexes in which four chiral cholesterol-functionalized sidearms were bundled
      and asymmetrically twisted above cyclen-metal complex platforms. Since the
      resulting helical metal complexes included chiral, hydrophobic cholesterol
      residues and charged, hydrophilic metal sites as well as asymmetric coordination
      geometries, they exhibited unique amphiphilic properties and provided chiral self
      aggregates in aqueous solutions. Light scattering, fluorescence, and TEM
      characterizations demonstrated that Na+ complex with cholesterol-armed cyclen
      gave a particularly stable self-aggregate in aqueous solution and offered
      supramolecular environments effective for sensing and detection of amino acid
      anions. Various dansylamino acid derivatives (dansyl = 5-(dimethylamino)-1
      naphthalenesulfonyl) were nicely accommodated in the helicate aggregates to give
      highly enhanced fluorescence signals, which could be detected by the naked eye at
      10(-7) mol/L level. Their inclusion behaviors were analyzed by a Langmuir-type
      equation, indicating that enantiomer-selective inclusion occurred. MM/MD
      calculations and circular dichroism (CD) studies further suggested that
      cholesterol-armed cyclen helicates have chiral and hydrophobic cavities upon self
      aggregation, in which the dansylamino acid anions were specifically accommodated.
      Since these helicates exhibited nonselective binding abilities in solvent
      extraction experiments of dansylamino acid anions, uncommon chiral recognition
      and sensing functions were generated by supramolecular alignments of the chiral
      metal helicates in the aqueous solutions.

PMID- 15730309
TI  - Synthesis and fluorescence of a series of multichromophoric acenaphthenyl
      compounds.
AB  - A novel free radical trapping reaction based on a stepwise radical reversible
      addition-fragmentation mechanism has been utilized to synthesize a series of
      acenaphthenyl dimers and trimers. The synthetic procedure involves the reaction
      of acenaphthylene with dithiobenzoate compounds (S=C(Ph)-SR) in the presence of a
      free radical initiator followed by reduction of the dithiobenzoyl end group with
      tributyltin hydride. Stereoisomers of the compounds have been isolated and their
      structures determined by proton NMR and X-ray crystallography. The solution
      fluorescence of the compounds has been characterized to reveal the requirements
      for intramolecular excimer (excited-state dimer) formation. Only in compounds
      containing identical stereochemical arrangements of adjacent acenaphthenyl groups
      is excimer fluorescence observed following photoexcitation.

PMID- 15730310
TI  - Generation and characterization of highly strained dibenzotetrakisdehydro[12]-
      and dibenzopentakisdehydro[14]annulenes.
AB  - To generate dibenzotetrakisdehydro[12]- and dibenzopentakisdehydro[14]annulenes
      ([12]- and [14]DBAs) having a highly deformed triyne moiety,
      [4.3.2]propellatriene-anneleted dehydro[12]- and dehydro[14]annulenes were
      prepared as their precursors. UV irradiation of the precursors resulted in the
      photochemical [2 + 2] cycloreversion to generate the strained [12]- and [14]DBAs,
      respectively. The [12]DBA was not detected by 1H NMR spectroscopy, but it was
      intercepted as Diels-Alder adducts in solution, suggesting its intermediacy. Its
      spectroscopic characterization was successfully carried out by UV-vis
      spectroscopy in a 2-methyltetrahydrofuran (MTHF) glass matrix at 77 K and by FT
      IR spectroscopy in an argon matrix at 20 K. On the other hand, the [14]DBA was
      stable enough for observation by 1H and 13C NMR spectra in solution, though it
      was not isolated because of the low efficiency of the cycloreversion. The [14]DBA
      was also characterized by interception as Diels-Alder adducts in solution and by
      UV-vis spectroscopy in a MTHF glass matrix at 77 K. The kinetic stabilities of
      the DBAs are compared with the related dehydrobenzoannulenes with respect to the
      topology of the pi-systems. In addition, the tropicity of the [14]DBA is
      discussed based on its experimental and theoretical 1H NMR chemical shifts.

PMID- 15730311
TI  - @-Tide-stabilized beta-hairpins.
AB  - As minimalist versions of beta-structure, two-stranded beta-hairpins are commonly
      employed as platforms for assessing the interactions that stabilize beta-sheets
      in proteins. We have found that the presence of a 1,6-dihydro-3(2H)-pyridinone
      moiety (the "@-unit") as an amino acid replacement at the i - 1 or i + 4
      positions relative to a beta-turn strongly stabilizes the hairpin conformation.
      Hybrids of this type bridge the gap between natural beta-hairpins and unnatural
      beta-sheets because the @-unit only replaces one residue in a peptide while
      stabilizing the hairpin conformation to a greater extent than a normal amino
      acid. In this report, we describe the synthesis of a variety of @-tide-templated
      hairpins and the NMR and CD characterization of their conformations in both polar
      and nonpolar solvents.

PMID- 15730312
TI  - Synthesis and application of phosphinoferrocenylaminophosphine ligands for
      asymmetric catalysis.
AB  - A new class of bidentate ligands utilizing a phosphine-aminophosphine structure
      has been prepared on a ferrocenylethyl backbone in a straightforward and scalable
      fashion from acetylferrocene. The unique property of the alpha-ferrocenyl
      carbonium ion that allows the replacement of a variety of "leaving groups" with
      retention of configuration greatly facilitates the synthesis, and a number of
      ligands have been prepared by varying the nitrogen and phosphorus substituents on
      the aminophosphine. These readily prepared phosphinoferrocenylaminophosphines,
      known as BoPhoz ligands, show surprising hydrolytic and air stability, with no
      degradation after 3 years open to the air. The rhodium complexes of these ligands
      show exceedingly high enantioselectivities (generally >95% ee) and activities
      often in excess of 50,000 catalyst turnovers per hour for the asymmetric
      hydrogenation of a wide variety of dehydro-alpha-amino acid and itaconic acid
      derivatives. They also show high activity and good to excellent
      enantioselectivity for the hydrogenation of a number of alpha-ketoesters.

PMID- 15730313
TI  - 1,4-Addition of benzene to a dihydrocyclopent[a]indene diradical: synthesis and
      DFT study.
AB  - Photochemical cyclization of compound 1, a homoenediyne (-CCC=CCH2CC-) bearing
      two ethynylanthracene chromophores, yields two isomeric dihydrocyclopent[a]indene
      ring systems, spiro-fused to the 9-position of a 9,10-dihydroanthracene moiety.
      Evidence of a photochemically initiated diradical cyclization pathway is proposed
      on the basis of (i) hydrogen abstraction from reaction with 1,4-cyclohexadiene
      (1,4-CHD) and (ii) the observation of 1,4-addition of benzene (solvent). The
      reaction was further analyzed by a complete density functional theory (DFT)
      study, using an unrestricted approach (UBLYP) with a 6-31G* basis set for the
      open-shell triplet states of the reactants, products, and diradical intermediates
      to model the photochemical nature of observed transformation. A mechanism
      detailing the observed cyclization/addition reaction is proposed.

PMID- 15730314
TI  - Aerobic catalytic photooxidation of olefins by an electron-deficient Pacman
      bisiron(III) mu-oxo porphyrin.
AB  - The synthesis and oxygen atom transfer (OAT) photoreactivity of a diiron(III) mu
      oxo meso-tripentafluorophenyl bisporphyrin appended to a dibenzofuran spacer are
      presented. Reaction of 4,6-diformyldibenzofuran under standard Lindsey conditions
      furnishes the parent cofacial porphyrin architecture in a single step. These
      cofacial porphyrins photocatalyze the oxidation of sulfides and olefins using
      visible light and molecular oxygen as the terminal oxidant. High turnover numbers
      reflect the enhanced stability of the electron-deficient diiron(III) mu-oxo
      bisporphyrin core appended to a dibenzofuran spacer under aerobic conditions.

PMID- 15730315
TI  - Grandisine A and B, novel indolizidine alkaloids with human delta-opioid receptor
      binding affinity from the leaves of the Australian rainforest tree Elaeocarpus
      grandis.
AB  - Two novel indolizidine alkaloids, grandisine A (1) and B (2), and the known
      alkaloid (-) isoelaeocarpiline (3) were isolated from the leaves of Elaeocarpus
      grandis and their structures determined by 1D and 2D NMR spectroscopy. The
      compounds showed affinity for the human delta-opioid receptor. Grandisine A
      contains a unique tetracyclic skeleton, while grandisine B possesses the unique
      combination of isoquinuclidinone and indolizidine groups in one molecule.

PMID- 15730316
TI  - Novel bromotyrosine derivatives that inhibit growth of the fish pathogenic
      bacterium Aeromonas hydrophila, from a marine sponge Hexadella sp.
AB  - Three new bromotyrosine derivatives, 11-N-methylmoloka'iamine (1), 11-N-cyano-11
      N-methylmoloka'iamine (2), and kuchinoenamine (3), were isolated as antibacterial
      constituents from a marine sponge Hexadella sp. Their structures were elucidated
      on the basis of spectral and chemical methods. They exhibited moderate
      antibacterial activity against the fish pathogenic bacterium Aeromonas
      hydrophila.

PMID- 15730317
TI  - Nonracemic Betti base as a new chiral auxiliary: application to total syntheses
      of enantiopure (2S,6R)-dihydropinidine and (2S,6R)-isosolenopsins.
AB  - Total syntheses of enantiopure alkaloidal natural products (2S,6R)
      dihydropinidine (as hydrochloride) and (2S,6R)-isosolenopsins (as hydrochlorides)
      were achieved in four steps and in 80-82% total yields by using a synthetic
      strategy of the formation-cleavage of 1,3-oxazinane. (S)-Betti base was proved to
      be an excellent chiral auxiliary and a novel Pd/C catalyzed N-debenzylation
      straightforward to amine hydrochloride was developed in the presence of CH2Cl2.

PMID- 15730318
TI  - Diastereoselective amidoalkylation of (3S,7aR)-6-benzyl-7-hydroxy-3-phenyltetra-
      hydro-5H-imidazo[1,5-c][1,3]thiazol-5-one: a short and highly efficient synthesis
      of (+)-biotin.
AB  - A short and highly efficient synthesis of (+)-biotin in 10 steps with 20% overall
      yield has been achieved from L-cysteine involving amidoalkylation of hydroxy
      imidazothiazolone 4 via an acyliminium ion intermediate to furnish C-7
      substituted imidazothiazolones 5b as the key step.

PMID- 15730319
TI  - Highly enantioselective phase-transfer catalytic alkylation in the preparation of
      non-natural alpha-amino acids via solid phase synthesis using aldimine linker.
AB  - A new Merrifield-resin-derived glycinimine tert-butyl ester (9) was prepared and
      applied to the enantioselective synthesis of non-natural alpha-amino acids. High
      enantioselectivities (86 to >99% ee) were accomplished by employing the aldimine
      linker under phase-transfer alkylation conditions, using 50% aqueous CsOH in
      toluene/chloroform (7:3) at 0 degrees C in the presence of N-(9
      anthracenylmethyl)-O(9)-allylcinchonidium bromide (10 mol %).

PMID- 15730320
TI  - Functionalization of the 6,14-bridge of the orvinols. 2. Preparation of 18- and
      19-hydroxyl-substituted thevinols and their treatment with benzyl bromide.
AB  - The etheno bridge of a thevinone was treated with BH3 and H2O2 to give both the
      18- and 19-hydroxyl- substituted thevinols. Selective benzylation of the primary
      20-hydroxyl over the 19-hydroxyl was successful; however, benzylation of the 18
      hydroxylated product led to a reaction at the more hindered alcohol. Thus, the
      6,14-bridge of the Diels-Alder products of thebaine can be hydroxylated, which
      opens up these positions for further chemical manipulation.

PMID- 15730321
TI  - A novel diastereoselective synthesis of (Z)-fluoroalkenes via a Nozaki-Hiyama
      Kishi-type reaction.
AB  - A highly diastereoselective and straightforward synthesis for (Z)-2-fluoroallylic
      alcohols via a Nozaki-Hiyama-Kishi-type reaction with the corresponding
      bromofluoroolefins was developed, providing an easy access to highly interesting
      fluorinated synthons.

PMID- 15730322
TI  - The 2-position of imidazolium ionic liquids: substitution and exchange.
AB  - The 2-position of imidazolium cations is known to be relatively acidic, leading
      to the useful Arduengo-type carbenes. At the same time, the acidity of this site
      can lead to undesired side reactions when using imidazolium-based ionic liquids
      as solvents. In this note, we describe the surprisingly facile deuterium exchange
      at this position and also the synthesis and exchange under modestly basic
      conditions (triethylamine) of a series of 2-methyl-substituted compounds.

PMID- 15730323
TI  - Strategies for the chemoenzymatic synthesis of deoxysugar nucleotides: substrate
      binding versus catalysis.
AB  - Sugar nucleotidyltransferases, also known as sugar pyrophosphorylases, catalyze
      the formation of a phosphate linkage to produce sugars activated for use by
      Leloir pathway glycosyltransferases and are subjects of protein engineering for
      chemoenzymatic synthesis strategies. Herein we present evidence that differences
      in substrate binding affinity do not primarily account for substantial contrasts
      in deoxysugar nucleotide product yields with this class of enzymes. Prokaryotic
      and eukaryotic glucose-1-phosphate uridylyltransferases (EC 2.7.7.9) can exercise
      kinetic discrimination in choosing carbohydrates of comparable binding affinity
      for catalytic turnover. These findings have implications for the in vivo and in
      vitro function and use of these enzymes.

PMID- 15730324
TI  - 7-endo selective aryl radical cyclization onto enamides leading to 3
      benzazepines: concise construction of a cephalotaxine skeleton.
AB  - Bu3SnH-mediated radical cyclizations of 2-(2-bromophenyl)-N-ethenylacetamide gave
      6-exo cyclization product 15 as the major product, whereas N-[2-(2
      bromophenyl)ethyl]-N-ethenylamides gave almost exclusively 7-endo cyclization
      products. These results indicated that the position of the carbonyl group on
      enamide played an important role in deciding the course of the cyclization. The 7
      endo selective cyclization was applied to concise construction of a cephalotaxine
      skeleton.

PMID- 15730325
TI  - Facile and highly selective conversion of nitriles to amides via indirect acid
      catalyzed hydration using TFA or AcOH-H2SO4.
AB  - Both aliphatic and aromatic nitriles are conveniently and selectively converted
      in a single step, via an indirect acid-catalyzed hydration, into the
      corresponding amides in 1-8 h using a TFA-H2SO4 mixture as a reagent system.
      Although the same reagent did not work for the sterically hindered nitriles such
      as mesitonitrile, the transformation could be accomplished by changing TFA to
      AcOH at higher temperatures (>90 degrees C).

PMID- 15730327
TI  - Surfactant/I2/water: an efficient system for deprotection of oximes and imines to
      carbonyls under neutral conditions in water.
AB  - I2/surfactant/water system deprotecting oximes and imines to the corresponding
      carbonyl compounds under neutral conditions in water at 25-40 degrees C with very
      high to excellent yields.

PMID- 15730326
TI  - Synthesis of 1-tert-butyl-4-chloropiperidine: generation of an N-tert-butyl group
      by the reaction of a dimethyliminium salt with methylmagnesium chloride.
AB  - Two efficient routes to 1-tert-butyl-4-chloropiperidine are described. In the
      first route, the key thionyl chloride mediated chlorination reaction features the
      use of tetrabutylammonium chloride as an additive that effectively suppresses the
      formation of an elimination-derived side product. In the second route, a novel
      alternative synthesis of 1-tert-butyl-4-chloropiperidine was developed in which
      the tertiary butyl group on the nitrogen is efficiently generated through the
      addition of methylmagnesium chloride to a dimethyliminium salt in 71% overall
      yield.

PMID- 15730328
TI  - Amination of N-aryl prolinol via ring expansion and contraction: application to
      the chiral ligand for the catalytic asymmetric reaction.
AB  - Chiral diaminophosphines 4 were prepared from (S)-prolinol-derived aminophosphine
      oxide 5 by bromination with ring expansion followed by amination with ring
      contraction and reduction, using trichlorosilane. In the presence of 4 as a
      ligand, palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2
      propenyl acetate (11) with a dialkyl malonate-BSA-LiOAc system was successfully
      carried out with good enantioselectivities (up to 98% ee).

PMID- 15730329
TI  - Efficient preparation of 2-indolyl-1-nitroalkane derivatives employing
      nitroalkenes as versatile Michael acceptors: new practical linear approach to
      alkyl 9h-beta-carboline-4-carboxylate.
AB  - The combination of cerium(III) chloride heptahydrate and sodium iodide supported
      on silica gel is known to promote Michael-type additions. Continuing our work on
      solvent-free conditions, the CeCl3.7H2O-NaI-SiO2 system catalyzes the addition of
      a variety of indoles and nitroalkenes, giving 2-indolyl-1-nitroalkane derivatives
      in good yields. Development of this method has resulted in a new protocol for the
      synthesis of 4-substituted beta-carbolines.

PMID- 15730330
TI  - Generation and reactions of two new functionalized tricyclo[3.3.0.0 3,7]oct-1(5)
      ene derivatives.
AB  - The generation of the new functionalized and highly pyramidalized alkenes, 3,7
      (2,2'-biphenylene)tricyclo[3.3.0.0(3,7)]oct-1(5)-ene (20) and 3,7
      sulfonyldioxytricyclo[3.3.0.0(3,7)]oct-1(5)-ene (39), and their trapping with 1,3
      diphenylisobenzofuran and 11,12-dimethylene-9,10-dihydro-9,10-ethanoanthracene
      are described. While both alkenes 20 and 39 failed to give the expected
      cyclobutane or diene dimers, 20 was reacted with 3,7
      dimethyltricyclo[3.3.0.0(3,7)]oct-1(5)-ene (1b) to give the cross-coupled product
      4,5-(2,2')-biphenylene-10,11
      dimethylpentacyclo[8.2.1.1(2,5).1(4,7).1(8,11)]hexadeca-1,7-diene (33). DFT
      calculations [B3LYP/6-31G(d)] on compound 20 gave important parameters of this
      pyramidalized alkene, such as the pyramidalization angle (61.7 degrees), the
      strain energy (72.9 kcal/mol), and the HOMO/LUMO gap (3.79 eV).

PMID- 15730331
TI  - Synthesis of a beta-amino acid pharmacophore via a beta-lactam intermediate.
AB  - A stereoselective synthesis of (R)-beta-amino acid 1 via a beta-lactam
      intermediate is discussed.

PMID- 15730332
TI  - Stille cross-coupling of activated alkyltin reagents under "ligandless"
      conditions.
AB  - Monoalkyltins activated by a fluoride source are shown to be as reactive as their
      vinyl or aryl homologues in the Stille coupling reaction, thus providing an easy
      entry into the pallado-catalyzed formation of Csp3-Csp2 bonds. In addition to
      this uncommon reactivity, this methodology holds several advantages such as (i) a
      quantitative preparation of stable and easy to handle alkyltin reagents 2, (ii) a
      simplified coupling procedure without any phosphine added ligand under neutral
      conditions, and (iii) a facile purification step of the organic products from the
      inorganic nontoxic tin byproducts.

PMID- 15730333
TI  - Efficient conversion of Biginelli 3,4-dihydropyrimidin-2(1H)-one to pyrimidines
      via PyBroP-mediated coupling.
AB  - An efficient two-step procedure is described to convert the Biginelli 3,4
      dihydropyrimidin-2(1H)-one to various multifunctionalized pyrimidines via the
      Kappe dehydrogenation and a new mild PyBroP-mediated coupling with C, N, O, and S
      nucleophiles, which provides a readily accessible multifunctionalized pyrimidine
      template for diversity-oriented synthesis.

PMID- 15730334
TI  - The chemistry of 4-azido-2-pyrimidinone nucleosides revisited.
AB  - Treatment of 4-azido-2-pyrimidinone nucleoside 1 with MeOH/K2CO3 or ammonium
      hydroxide led to derivatives 2 and 3, respectively. Both compounds derived from a
      nucleophilic addition at the modified base 2-position. These results contrast
      with the previously reported sensitivity of the 4-azido-2-pyrimidinone nucleoside
      6-position to nucleophiles.

PMID- 15730335
TI  - Pulmonary oedema of immersion.
AB  - Acute pulmonary oedema has been described in individuals participating in three
      aquatic activities: (i) scuba diving; (ii) breath-hold diving; and (iii)
      endurance swimming. In this review, 60 published cases have been compiled for
      comparison. Variables considered included: age; past medical history; activity;
      water depth, type (salt or fresh) and temperature; clinical presentation;
      investigations; management; and outcome. From these data, we conclude that a
      similar phenomenon is occurring among scuba, breath-hold divers and swimmers. The
      pathophysiology is likely a pulmonary overperfusion mechanism. High pulmonary
      capillary pressures lead to extravasation of fluid into the interstitium. This
      overperfusion is caused by the increase in ambient pressure, peripheral
      vasoconstriction from ambient cold, and increased pulmonary blood flow resulting
      from exercise. Affected individuals are typically healthy males and females.
      Older individuals may be at higher risk. The most common symptoms are cough and
      dyspnoea, with haemoptysis also a frequent occurrence. Chest pain has never been
      reported. Radiography is the investigation of choice, demonstrating typical
      findings for pulmonary oedema. Management is supportive, with oxygen the mainstay
      of treatment. Cases usually resolve within 24 hours. In some cases, diuretics
      have been used, but there are no data as to their efficacy. Nifedipine has been
      used to prevent recurrence, but there is only anecdotal evidence to support its
      use.

PMID- 15730336
TI  - Does neuromuscular electrical stimulation strengthen the quadriceps femoris? A
      systematic review of randomised controlled trials.
AB  - Devices for neuromuscular electrical stimulation (NMES) are increasingly used by
      individuals without specific injuries and are standard equipment in most physical
      therapy practices. The most often stimulated muscle group is the quadriceps
      femoris. We designed a systematic review and meta-analysis of randomised
      controlled trials to determine whether NMES is an effective modality for strength
      augmentation of the quadriceps femoris. A full content search for randomised
      controlled trials was performed in Medline, Embase, Cinahl, the Cochrane
      Controlled Trials Register and the Physical Therapy Evidence Database. Maximum
      volitional isometric or isokinetic muscle torque in Nm was used as main outcome
      measure.Thirty-five trials were included and evaluated. A fundamental distinction
      was made between the trials using subjects with unimpaired quadriceps femoris
      muscles and the trials using post-injury or post-operative subjects. In the
      unimpaired quadriceps subgroup, meta-analyses were performed for the comparisons
      'NMES versus no exercises' and 'NMES versus volitional exercises'. All other
      comparisons were evaluated descriptively. The included trials were generally of
      poor quality and meta-analytic data indicate that publication bias may be
      present. The evaluated data suggest that, both for the unimpaired and impaired
      quadriceps, NMES makes sense compared with doing no exercises but volitional
      exercises appear to be more effective in most situations.Based on the available
      evidence, NMES may only be preferred over volitional training for within-cast
      muscle training and perhaps in specific situations where volitional training does
      not receive sufficient patient compliance. Further research should be directed
      toward identifying the clinical impact at activity and participation levels and
      the optimal stimulation parameters of this modality.

PMID- 15730337
TI  - Challenges in understanding the influence of maximal power training on improving
      athletic performance.
AB  - The ability to optimise muscular power output is considered fundamental to
      successful performance of many athletic and sporting activities. Consequently, a
      great deal of research has investigated methods to improve power output and its
      transference to athletic performance. One issue that makes comparisons between
      studies difficult is the different modes of dynamometry (isometric, isokinetic
      and isoinertial) used to measure strength and power. However, it is recognised
      that isokinetic and isometric assessment bear little resemblance to the
      accelerative/decelerative motion implicit in limb movement during resistance
      training and sporting performance. Furthermore, most people who train to increase
      power would have limited or no access to isometric and/or isokinetic dynamometry.
      It is for these reasons and for the sake of brevity that the findings of
      isoinertial (constant gravitational load) research will provide the focus of much
      of the discussion in this review. One variable that is considered important in
      increasing power and performance in explosive tasks such as running and jumping
      is the training load that maximises the mechanical power output (Pmax) of muscle.
      However, there are discrepancies in the research as to which load maximises power
      output during various resistance exercises and whether training at Pmax improves
      functional performance is debatable. There is also some evidence suggesting that
      Pmax is affected by the training status of the individuals; however, other
      strength variables could quite possibly be of greater importance for improving
      functional performance. If Pmax is found to be important in improving athletic
      performance, then each individual's Pmax needs to be determined and they then
      train at this load. The predilection of research to train all subjects at one
      load (e.g. 30% one repetition maximum [1RM]) is fundamentally flawed due to inter
      individual Pmax differences, which may be ascribed to factors such as training
      status (strength level) and the exercise (muscle groups) used. Pmax needs to be
      constantly monitored and adjusted as research suggests that it is transient. In
      terms of training studies, experienced subjects should be used, volume equated
      and the outcome measures clearly defined and measured (i.e. mean power and/or
      peak power). Sport scientists are urged to formulate research designs that result
      in meaningful and practical information that assists coaches and strength and
      conditioning practitioners in the development of their athletes.

PMID- 15730338
TI  - The mechanisms of massage and effects on performance, muscle recovery and injury
      prevention.
AB  - Many coaches, athletes and sports medicine personnel hold the belief, based on
      observations and experiences, that massage can provide several benefits to the
      body such as increased blood flow, reduced muscle tension and neurological
      excitability, and an increased sense of well-being. Massage can produce
      mechanical pressure, which is expected to increase muscle compliance resulting in
      increased range of joint motion, decreased passive stiffness and decreased active
      stiffness (biomechanical mechanisms). Mechanical pressure might help to increase
      blood flow by increasing the arteriolar pressure, as well as increasing muscle
      temperature from rubbing. Depending on the massage technique, mechanical pressure
      on the muscle is expected to increase or decrease neural excitability as measured
      by the Hoffman reflex (neurological mechanisms). Changes in parasympathetic
      activity (as measured by heart rate, blood pressure and heart rate variability)
      and hormonal levels (as measured by cortisol levels) following massage result in
      a relaxation response (physiological mechanisms). A reduction in anxiety and an
      improvement in mood state also cause relaxation (psychological mechanisms) after
      massage. Therefore, these benefits of massage are expected to help athletes by
      enhancing performance and reducing injury risk. However, limited research has
      investigated the effects of pre-exercise massage on performance and injury
      prevention. Massage between events is widely investigated because it is believed
      that massage might help to enhance recovery and prepare athletes for the next
      event. Unfortunately, very little scientific data has supported this claim. The
      majority of research on psychological effects of massage has concluded that
      massage produces positive effects on recovery (psychological mechanisms). Post
      exercise massage has been shown to reduce the severity of muscle soreness but
      massage has no effects on muscle functional loss. Notwithstanding the belief that
      massage has benefits for athletes, the effects of different types of massage
      (e.g. petrissage, effleurage, friction) or the appropriate timing of massage (pre
      exercise vs post-exercise) on performance, recovery from injury, or as an injury
      prevention method are not clear. Explanations are lacking, as the mechanisms of
      each massage technique have not been widely investigated. Therefore, this article
      discusses the possible mechanisms of massage and provides a discussion of the
      limited evidence of massage on performance, recovery and muscle injury
      prevention. The limitations of previous research are described and further
      research is recommended.

PMID- 15730344
TI  - Dynamics of the Ins(1,4,5)P3 receptor during polarization of MDCK cells.
AB  - BACKGROUND INFORMATION: The uneven distribution of the Ins(1,4,5)P3R
      [Ins(1,4,5)P3 receptor] within the ER (endoplasmic reticulum) membrane generates
      spatially complex Ca2+ signals. The ER is a dynamic network, which allows the
      rapid diffusion of membrane proteins from one part of the cell to another.
      However, little is known about the localization and the dynamics of the
      Ins(1,4,5)P3R in the ER of living cells. We have used a MDCK (Madin-Darby canine
      kidney) clone stably expressing the Ins(1,4,5)P3R1-GFP (where GFP stands for
      green fluorescent protein) to investigate the effect of cell polarity on the
      lateral mobility of the Ins(1,4,5)P3R. RESULTS: In non-confluent MDCK cells, the
      chimaera is homogeneously distributed throughout the ER and the nuclear envelope.
      FRAP (fluorescence recovery after photobleaching) experiments showed that the
      receptor can move freely in the ER with a diffusion constant (D=0.01 microm2/s)
      approx. ten times lower than other ER membrane proteins. In confluent polarized
      cells, two populations of receptor can be defined: one population is distributed
      in the cytoplasm and is mobile but with a slower diffusion constant (D=0.004
      microm2/s) compared with non-confluent cells, whereas the other population is
      concentrated at the periphery of the cells and is apparently immobile.
      CONCLUSIONS: The observed differences in the mobility of the Ins(1,4,5)P3R are
      most probably due to its interactions with stable protein complexes that form at
      the periphery of the polarized cells.

PMID- 15730339
TI  - Interaction between alcohol and exercise: physiological and haematological
      implications.
AB  - Alcohol use, particularly excessive alcohol consumption is one of the most
      serious health risks in the world. A relationship between sport, exercise and
      alcohol consumption is clear and long-standing. Alcohol continues to be the most
      frequently consumed drug among athletes and habitual exercisers and alcohol
      related problems appear to be more common in these individuals. Alcohol use is
      directly linked to the rate of injury sustained in sport events and appears to
      evoke detrimental effects on exercise performance capacity. The model of alcohol
      consumption in human experimental studies has either been acute (single dose) or
      chronic (repeated doses over a period). These studies suggested that alcohol
      consumption decreases the use of glucose and amino acids by skeletal muscles,
      adversely affects energy supply and impairs the metabolic process during
      exercise. In addition, chronic alcohol use is associated with increased citrate
      synthase activity and decreased cross-sectional area of type I, IIa and IIb
      fibres. There is evidence to suggest that exercise may attenuate the ethanol
      induced decline in hepatic mitochondria and accelerates ethanol metabolism by the
      liver. Exercise training seems to reduce the extent of the oxidative damage
      caused by ethanol. Evidence generated from in vitro experiments and animal
      studies have also suggested that ethanol administration decreased skeletal muscle
      capillarity and increased pyruvate kinase and lactate dehydrogenase activities.
      Substantial epidemiological evidence has been accrued showing that moderate
      ingestion of alcohol may reduce the incidence of cardiovascular diseases.
      Although the existing evidence is often confusing and disparate, one of the
      mechanisms by which alcohol may reduce the incidence of mortality of
      cardiovascular diseases is through raising levels of high-density lipoprotein
      cholesterol. Available evidence suggests that exercise and moderate alcohol
      consumption may have favourable effects on blood coagulation and fibrinolysis;
      however, compelling experimental evidence is lacking to endorse this notion.
      Occasional and chronic alcohol consumption is usually linked with unfavourable
      alterations in platelet aggregation and function and may be associated with
      platelet-related thrombus formation. Although the effects of alcohol consumption
      on the rheological properties of the blood are not known, recent experimental
      evidence suggests that alcohol use following exercise is associated with
      unfavourable changes in the main determinants of blood viscosity. It is well
      documented that alcohol use modulates the immune system and impairs host defence.
      Compelling evidence is also mounting to suggest that chronic alcohol use is
      linked with adverse effects on the body systems and organs including the brain,
      the cardiovascular system and the liver.

PMID- 15730345
TI  - Training and aging modulate the loss-of-balance phenotype observed in a new ENU
      induced allele of Otopetrin1.
AB  - BACKGROUND INFORMATION: The sensing of head movement in mammals depends upon the
      vestibular endorgan of the inner ear, a complex structure made up of the
      semicircular canals and otoliths. Due to the similarity between the human and
      mouse vestibular apparatus, the analysis of mutant mouse is a valuable strategy
      aiming to identify genes involved in the control of balance and movement.
      RESULTS: In the course of a genome-wide chemical-mutagenesis programme, we
      isolated a recessive mutation, named ied (inner ear defect), which induced a
      severe loss-of-balance. A detailed phenotypic analysis of the mutant mice
      demonstrates that the balance impairment does not affect the motor activity and
      can be rescued, in part, by training, despite a complete agenesis of otoconia in
      the utricule and the saccule of the inner ear. Molecular characterization of the
      ied mutation revealed a transversion that affects the splicing of the second exon
      of the Otopetrin1 gene located on mouse chromosome 5. The consequence of such a
      mutation leads to a disruption of the transcription of the gene. CONCLUSIONS: The
      identification of the ied knock-down allele strengthens the role of the
      Otopetrin1 in the sensing of balance. Moreover, the rescue of the ied mutant
      phenotype in specific behavioural tasks confirmed that other sensory inputs or
      neural plasticity can compensate, to some extent, for the loss-of-balance. In the
      future, the ied mutant mice might be helpful to study the genetic control of the
      compensation strategies developed by organisms to counteract balance defects.

PMID- 15730347
TI  - Nefazodone treatment of cocaine dependence with comorbid depressive symptoms.
AB  - AIMS: In the current study, nefazodone, an antidepressant with dual action on
      serotonin and norepinephrine reuptake as well as 5-HT(2A) receptor antagonist
      effects, was studied in subjects with cocaine dependence and depressive symptoms,
      to determine its efficacy in reducing cocaine use. DESIGN: An 8-week, double
      blind, placebo-controlled design was used. SETTING: The study was conducted at
      the Medication Development Research Unit (MDRU) at the VA Boston Healthcare
      System and the Manhattan Department of Veterans Affairs (DVA) Medical Center.
      PARTICIPANTS: Subjects (n = 69) met Diagnostic and Statistical Manual version IV
      (DSM-IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12
      or higher. INTERVENTION: Subjects were assigned randomly to receive nefazodone
      200 mg twice daily (n = 34) or matching placebo (n = 35). All subjects received
      individual counseling. MEASUREMENTS: Urinary measurements of benzoylecgonine (BE,
      three times per week) and self-reports of cocaine use were the primary outcome
      measures. Secondary outcome measures included assessments of psychiatric
      functioning, cocaine craving and social functioning. FINDINGS: Median weekly BE
      declined more rapidly in the nefazodone than in the placebo group. Median urine
      BE at baseline was, however, significantly greater in nefazodone than in the
      placebo group. Scores for strength of cocaine craving also decreased more rapidly
      in the nefazodone group compared to the placebo group. Both groups had equivalent
      improvement in mood, psychosocial functioning and self-reported cocaine use.
      CONCLUSIONS: These results suggest that nefazodone administration can reduce
      cocaine craving after it has been administered for several weeks. Although the
      nefazodone group had a greater rate of decrease in BE levels than the placebo
      group, the interpretation of this finding is obscured by significant group
      differences in baseline BE levels.

PMID- 15730346
TI  - Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole
      and venlafaxine in cocaine dependence.
AB  - AIMS: The two studies presented here were conducted to assess the efficacy of
      paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications
      for the treatment of cocaine dependence. DESIGN: A multi-arm, modified blinded,
      placebo-controlled design was used. SETTING: The studies were conducted at the
      Boston VA Healthcare System and the Boston University School of Medicine
      Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met
      criteria for cocaine dependence during a 2-week screening period. INTERVENTION:
      Following random assignment to one of the treatment groups, subjects received
      active medication or placebo for 8 weeks in combination with cognitive behavioral
      counseling. In the first study the efficacy of the antidepressant paroxetine (20
      mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the
      glutamate release inhibitor riluzole (100 mg daily) was assessed. The
      antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole
      (1.5 mg daily) were evaluated in the second study. MEASUREMENTS: Urine
      benzoylecgonine (BE) concentrations, self-report of cocaine use and global
      impression scores served as primary outcome measures. Secondary measures included
      assessments of cocaine craving and psychiatric functioning. Adverse events were
      monitored during the treatment period. FINDINGS: None of the active medications
      produced greater reductions in urine BE concentrations over the treatment period
      than did placebo. There were trends for BE levels to become reduced in the
      pentoxifylline group during the first 4 weeks of treatment and for Addiction
      Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline
      group at end-point compared to the placebo group. Significant within-group
      reductions in reported cocaine use and craving were found for all treatment
      groups, but none of the active medications were superior to placebo on these
      measures. The accuracy of self-reported cocaine use declined over the study
      period. Overall, the active medications were well tolerated. CONCLUSIONS: This
      study does not support the use of paroxetine, pentoxifylline, riluzole,
      venlafaxine or pramipexole for the treatment of cocaine dependence. However,
      these results need to be interpreted with caution because of the small size and
      lack of homogeneity of the experimental groups.

PMID- 15730348
TI  - A placebo-controlled screening trial of celecoxib for the treatment of cocaine
      dependence.
AB  - AIMS: To conduct a medication screening trial study on the efficacy of celecoxib
      versus placebo for the treatment of cocaine dependence. DESIGN: A modified
      blinded, parallel group study in an outpatient setting using the Cocaine Rapid
      Efficacy and Safety Trials (CREST) study design. SETTING: The study was performed
      at the New York Medications Development Research Unit (MDRU). PARTICIPANTS: All
      participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria
      for cocaine dependence and provided at least two urine samples positive for
      benzoylecgonine (BE) during the 2-week screening period. Twenty-three
      participants were enrolled in the treatment phase of the study. INTERVENTION:
      After a 2-week screening period, subjects were assigned randomly to receive
      either celebrex (200 mg/day) or placebo for an 8-week treatment period. All
      subjects also received individual cognitive behavioral counseling during
      treatment. MEASUREMENTS: Primary outcome measures included quantitative urine
      benzoylecgonine (BE) levels, self-report of drug use and global impression
      scores. Secondary outcomes included cocaine craving, study retention and related
      psychosocial measures. Safety measures included adverse event monitoring, vital
      signs and extrapyramidal side-effects tests. RESULTS: Study retention was similar
      across both treatment groups and safety measures indicated that celecoxib was
      moderately tolerated. Cocaine use, as measured by self-report and urine BE levels
      at end of treatment, indicated weaker improvement in the celecoxib group.
      Reductions in the intensity of cocaine craving were also weaker in the celecoxib
      group. Cocaine abstinence rates, global impression scores and all other related
      psychometric measures did not differ significantly between treatment groups.
      CONCLUSION: This study does not support the effectiveness of celecoxib for the
      treatment of cocaine dependence.

PMID- 15730349
TI  - A placebo-controlled screening trial of olanzapine, valproate, and coenzyme Q10/L
      carnitine for the treatment of cocaine dependence.
AB  - AIMS: To conduct a medication screening trial on the efficacy of olanzapine,
      valproate or coenzyme Q10/L-carnitine combination versus placebo for the
      treatment of cocaine dependence. DESIGN: A four-arm, modified blinded, parallel
      group study in an out-patient setting using the Cocaine Rapid Efficacy and Safety
      Trials (CREST) study design. SETTING: The study was performed at the New York
      Medications Development Research Unit (MDRU). PARTICIPANTS: All participants met
      Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine
      dependence and provided at least two urine samples positive for benzoylecgonine
      (BE) during the 2-week screening period. Sixty-eight participants were enrolled
      with 39 completing the study. INTERVENTION: After a 2-week screening period, 68
      subjects were assigned randomly to receive either olanzapine (10 mg/day),
      valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L-carnitine (500 mg/day)
      combination or placebo for an 8-week treatment period. All subjects also received
      individual cognitive behavioral counseling during treatment. MEASUREMENTS:
      Primary outcome measures included quantitative urine benzoylecgonine (BE) levels,
      self-report of drug use, and global impression scores. Secondary outcomes
      included cocaine craving, study retention and related psychosocial measures.
      Safety measures included adverse event monitoring, vital signs, and
      extrapyramidal side-effects tests. RESULTS: Study retention was similar across
      all treatment groups, and all groups showed improvement across most measures of
      treatment efficacy over the duration of the study. None of the study medications,
      however, were superior to placebo on any of the primary or secondary outcome
      measures. Cocaine use, as measured by urine BE levels and self-report, was not
      significantly lower than placebo in any of the drug treatment groups. All study
      medications were equally well tolerated, and few medication side effects were
      observed. CONCLUSION: This pilot study does not support the effectiveness of
      olanzapine, valproate or coenzyme Q10/L-carnitine combination for the treatment
      of cocaine dependence.

PMID- 15730350
TI  - A medication screening trial evaluation of reserpine, gabapentin and lamotrigine
      pharmacotherapy of cocaine dependence.
AB  - AIMS: To conduct a preliminary evaluation of the safety and efficacy of
      reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a
      treatment for cocaine dependence. DESIGN: A 10-week out-patient study using the
      Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: The study
      was conducted at the Cincinnati Medication Development Research Unit (MDRU).
      PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM
      IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50
      participants completing the final study measures. INTERVENTION: The targeted
      daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and
      lamotrigine 150 mg. All participants received 1 hour of manualized individual
      cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome
      measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical
      Global Impression scale--observer and self-report of cocaine use. Safety measures
      included adverse events, electrocardiograms (ECGs), vital signs and laboratory
      tests. FINDINGS: Subjective measures of cocaine dependence indicated significant
      improvement for all study groups. Urine BE results indicated a significant
      improvement for the reserpine group (P < 0.05) and non-significant changes for
      the other study groups. No pattern of physical or laboratory abnormalities
      attributable to treatment with any of the medications was identified. There were
      three serious adverse events reported, none of which were related to study
      procedures. The medications appeared to be tolerated well. CONCLUSIONS: The
      present findings suggest that reserpine may be worthy of further study as a
      cocaine dependence treatment.

PMID- 15730351
TI  - A placebo-controlled screening trial of tiagabine, sertraline and donepezil as
      cocaine dependence treatments.
AB  - AIMS: To conduct a preliminary evaluation of the safety and efficacy of
      tiagabine, sertraline or donepezil versus an unmatched placebo control as a
      treatment for cocaine dependence. DESIGN: A 10-week out-patient study was
      conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.
      SETTING: This study was conducted at the Cincinnati Medication Development
      Research Unit (MDRU) and at an affiliated site in Dayton, Ohio. PARTICIPANTS:
      Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria
      for cocaine dependence. Sixty-seven participants were enrolled with 55 completing
      final study measures. INTERVENTION: The targeted daily doses of medication were
      tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received
      1 hour of manualized individual cognitive behavioral therapy on a weekly basis.
      MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine
      (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of
      cocaine use. Safety measures included adverse events, ECGs, vital signs and
      laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated
      significant improvement for all study groups. Generalized estimating equations
      analysis indicated that the tiagabine group showed a trend toward a significant
      decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non
      significant changes for the other study groups. No pattern of physical or
      laboratory abnormalities attributable to treatment with any of the medications
      was identified. There were three serious adverse events reported, none of which
      were related to study procedures. CONCLUSIONS: The present findings suggest that
      tiagabine may be worthy of further study as a cocaine dependence treatment.

PMID- 15730352
TI  - Randomized controlled pilot trial of cabergoline, hydergine and
      levodopa/carbidopa: Los Angeles Cocaine Rapid Efficacy Screening Trial (CREST).
AB  - AIM: This study tested three dopaminergic medications against a common unmatched
      placebo condition: hydergine 1 mg three times daily (n = 15); levodopa/carbidopa
      25/100 mg three times daily (n = 15); cabergoline 0.5 mg per week (n = 15); and
      placebo three times daily (n = 15) as potential pharmacotherapies for cocaine
      dependence. DESIGN: The four-parallel group, Cocaine Rapid Efficacy Screening
      Trial (CREST) design featured a 2-week baseline period followed by randomization
      to an 8-week medication condition that included 1 hour per week of cognitive
      behavioral drug counseling. A safety evaluation was conducted 4 weeks after
      termination. MEASURES: Outcomes included cocaine metabolites measured in urine,
      retention and self-reports for drug use, cocaine craving, clinical improvement,
      mood and HIV risk behaviors. RESULTS: Participants assigned to receive
      cabergoline provided more urine samples negative for cocaine metabolites (42.4%)
      than those assigned to receive placebo (25.0%), a statistically significant
      difference after controlling for baseline differences in self-reported cocaine
      use (F = 2.95, df = 3; P = 0.05). Cabergoline-treated participants demonstrated a
      significant improvement over placebo from baseline to week 8 when measured using
      the Addiction Severity Index (ASI) employment subscale (overall change = - 0.09,
      SD = 0.10, t = 2.36, P < 0.05). Safety and adverse event measures showed similar
      rates and types of complaints by treatment condition. CONCLUSIONS: These results,
      combined with the apparent safety of cabergoline when used with this population,
      provide empirical support for conducting a larger study of the medication.

PMID- 15730353
TI  - Retrospective analyses of pooled data from CREST I and CREST II trials for
      treatment of cocaine dependence.
AB  - AIM: To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial
      (CREST). Pooling data from these small pilot trials into four major drug classes
      permitted data exploration for treatment and covariate effects with increased
      sample size. DESIGN: Small pilot trials were conducted to screen fifteen
      medications as prospective treatments for cocaine dependence. Studies included a
      flexible 2-week to 4-week screening/baseline period followed by an 8-week
      randomized treatment condition. Participants were randomized equally to one of up
      to three active medications or placebo. SETTING: Five Medications Development
      Research Units at the five academic centers of University of Cincinnati, New York
      University, University of Pennsylvania, University of California Los Angeles and
      Boston University. PARTICIPANTS: The pooled data set consisted of 357 total
      subjects. Standardized inclusion and exclusion criteria were employed in subject
      selection to enhance consistency of cocaine-dependent study participants across
      all sites (see reports on individual trials in this supplement for details). All
      participants provided at least two urine samples that were positive for cocaine
      metabolite during a two-week period prior to being randomized. INTERVENTION: All
      subjects in these trials, those randomized to placebo and active medications,
      received active treatment in the form of evidence-based cognitive behavioral
      therapy. MEASURES: Quantitative urine benzoylecgonine (BE), self-report of
      cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared
      between each class of medication and its matched-placebo group. FINDINGS:
      Regression analysis of pooled data did not identify any statistically significant
      differences between treatment and matched-placebo for any of the four classes.
      Exploration of the effects of baseline covariates indicated that gender and
      African American status were associated significantly with outcome. Female gender
      was consistently associated with poorer outcomes for medication and placebo
      groups, while the direction of association between African American status and
      outcome differed by treatment groups. Retention was also examined: dropout rates
      may have been somewhat higher for placebo than treatment groups during the early
      active-treatment period. Classification trees were used to identify
      characteristics of subjects who were abstinent for at least two weeks during the
      eight-week trial; only 4.0% of females while 17.9% of males achieved this
      criterion. CONCLUSIONS: Results presented here may prove useful for planning
      future clinical trials for therapies targeting cocaine dependence.

PMID- 15730354
TI  - Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned.
AB  - AIMS: The Cocaine Rapid Efficacy Screening Trials (CREST) were designed by the
      National Institute on Drug Abuse Division of Treatment Research and Development
      (NIDA, DT R&D) to rapidly screen a number of medications potentially useful for
      the treatment of cocaine dependence. DESIGN: Each CREST trial was designed to
      compare several medications in a single trial against an unmatched placebo. The
      placebo group was included in each trial to avoid the nearly universal positive
      response to medications seen in open-label trials. In addition, a common set of
      procedures and outcome measures were employed throughout to increase
      comparability of results obtained from different trials and from different times.
      PARTICIPANTS: In all, 18 medications were screened in seven different trials,
      conducted in four different sites throughout the United States involving 398
      cocaine-dependent patients. FINDINGS: Three medications were found to be
      promising enough to include in subsequent larger trials. Common statistical
      procedures for evaluating medications were developed to facilitate comparisons
      across sites and across time. A portion of the data were pooled and analyzed,
      which yielded some useful insights into cocaine dependence and its treatment.
      Finally, a review of individual trials together with the pooled analysis revealed
      several potential improvements for future screening trials. CONCLUSIONS: Overall,
      the CREST trials proved to be useful for rapidly screening medications for
      treatment of cocaine dependence, but several modifications in design should be
      made before this framework is applied further.

PMID- 15730355
TI  - Editorial comment.

PMID- 15730356
TI  - Coat of arms of The Royal Australian and New Zealand College of Obstetricians and
      Gynaecologists (RANZCOG).

PMID- 15730357
TI  - Pelvic floor trauma in childbirth - myth or reality?
AB  - The issue of traumatic damage to the pelvic floor in childbirth is attracting
      more and more attention amongst obstetric caregivers and laypersons alike. This
      is partly due to the fact that elective Caesarean section, as a potentially
      preventative intervention, is increasingly available and perceived as safe. As
      there are a multitude of emotive issues involved, including health economics and
      the relative roles of healthcare providers, the discussion surrounding pelvic
      floor trauma in childbirth has not always been completely rational. However,
      after 25 years of urogynaecological research in this field it should be possible
      to determine whether pelvic floor trauma in childbirth is myth or reality. On
      reviewing the available evidence, it appears that there are sufficient grounds to
      assume that vaginal delivery (or even the attempt at vaginal delivery) can cause
      damage to the pudendal nerve, the caudal aspects of the levator ani muscle,
      fascial pelvic organ supports and the external and internal anal sphincter. Risk
      factors for such damage have been defined and variously include operative vaginal
      delivery, a long second stage, and macrosomia. It is much less clear, however,
      whether such trauma is clinically relevant, and how important it is in the
      aetiology of pelvic floor morbidity later in life.

PMID- 15730358
TI  - Pregnancy outcomes in women of very advanced maternal age.
AB  - OBJECTIVE: To assess outcomes for pregnancies progressing beyond 20 weeks'
      gestation in women of very advanced maternal age. DESIGN: Retrospective cohort
      study. SETTING: Two tertiary level obstetric hospitals. POPULATION: Women aged 45
      years or more at the time of delivery over a 10-year period from 1 January 1992
      to 31 December 2001. METHODS: Information regarding maternal, pregnancy and
      neonatal outcomes was obtained from the medical records. For comparison,
      routinely collected data from the obstetric database was obtained for women aged
      20-29 years. RESULTS: Seventy-seven pregnancies in 76 women aged 45 years and
      over were registered in the 10-year period. There were 74 liveborn singletons,
      two sets of liveborn twins and one set of twins stillborn at 20 weeks' gestation.
      Sixteen women were primiparous. Eighty-four percent of pregnancies were conceived
      naturally and 53% underwent prenatal chromosomal determination; 53% of women had
      no pre-existing medical problems, 13% had hypertensive disorders of pregnancy and
      8% of women developed gestational diabetes. There were 10 preterm and six post
      dates deliveries. The Caesarean section rate was 49%, compared to 23% in the 20
      29 years age group (P < 0.001). Ten percent of neonates were small for
      gestational age, and 8% were large for gestational age. Seventeen percent
      required admission to the special care nursery and 6% had congenital
      abnormalities. CONCLUSIONS: Maternal and neonatal outcomes in this series were
      generally good. There was a significantly increased rate of Caesarean section.
      Overall, this study is reassuring for women aged 45 and over who have good
      general health and a chromosomally normal fetus.

PMID- 15730359
TI  - Incidence of polycystic ovaries and polycystic ovary syndrome amongst women in
      Melbourne, Australia.
AB  - BACKGROUND: The incidence of polycystic ovaries (PCO) in the Australian
      population is unknown. AIMS: To determine the incidence of PCO in a random
      population of Melbourne women. METHODS: A retrospective survey of the
      transvaginal ultrasound of female partners of sterile males was undertaken.
      RESULTS: Twenty-three percent of subjects had polycystic ovaries on ultrasound
      criteria, 17% bilateral and 6% unilateral. CONCLUSIONS: The incidence of PCO in
      Australian women is similar to that of other Caucasian populations.

PMID- 15730360
TI  - Anti-mullerian hormone as a marker of ovarian reserve.
AB  - OBJECTIVE: To analyse the usefulness of plasma anti-mullerian hormone (AMH)
      measurement as a tool for assessing ovarian reserve in a general infertility
      population. MATERIALS AND METHODS: Plasma AMH levels were analysed in 238 women
      aged 18-46 years during day 3-5 of their menstrual cycle. All 238 patients had
      follicle stimulating hormone (FSH) levels less than 10 i.u./L, suggesting normal
      ovarian reserve on traditional FSH criteria. Eighty-seven patients gave their
      consent to correlate their AMH levels with IVF oocyte retrieval outcome. Patients
      producing > or = 8 oocytes were classified as having normal ovarian reserve,
      while those producing < or = 4 oocytes were classified as having poor ovarian
      reserve. RESULTS: Plasma AMH levels remained relatively static (20-25 pmol/L)
      from 18 to 29 years of age. By 30 years of age, plasma AMH levels start to drop
      rapidly, reaching only 10 pmol/L by 37 years. Despite this 50% fall in AMH levels
      between 29 and 37 years of age, minimal changes in FSH levels were observed.
      Using a cut off value of 8.1 pmol/L, plasma AMH assessment could predict poor
      ovarian reserve on a subsequent IVF cycle with a sensitivity of 80% and a
      specificity of 85%. CONCLUSIONS: Plasma AMH assessments are superior to FSH in
      identifying women with reduced ovarian reserve. Anti-mullerian hormone assessment
      should be considered as a useful adjunct to FSH/oestradiol levels and antral
      follicle count when estimating ovarian reserve.

PMID- 15730361
TI  - Misoprostol for second and third trimester termination of pregnancy: a review of
      practice at the Women's and Children's Hospital, Adelaide, Australia.
AB  - AIMS: To assess clinical outcomes for women undergoing induction of labour either
      for fetal anomaly or following intrauterine fetal death using intravaginal
      misoprostol. METHODS: Between January 1999 and December 2002, clinical outcomes
      for women who were admitted to the delivery suite of the Women's and Children's
      Hospital, South Australia, were prospectively collected and entered onto a
      database by the attending midwife. The effect of cumulative dose of misoprostol,
      indication for induction of labour, parity and gestational age were assessed.
      RESULTS: One hundred and ninety nine women were admitted during the study period.
      Women who required in excess of 800 microg of misoprostol were more likely to
      have side-effects (57/78 women dose > 800 microg misoprostol versus 71/121 women
      dose < or = 800 microg, RR 0.80 95% CI 0.66-0.98), in particular diarrhoea (12/78
      women dose > 800 microg misoprostol versus 5/121 women dose < or = 800 microg, RR
      0.27 95% CI 0.10-0.73) and elevated temperature (46/78 women dose > 800 microg
      misoprostol versus 36/121 women dose < or = 800 microg, RR 0.50 95% CI 0.36
      0.70). Women with an intrauterine fetal death (IUFD) were less likely to require
      in excess of 800 microg of misoprostol to effect the termination (10/56 women
      IUFD versus 70/143 women fetal anomaly, RR 0.36 95% CI 0.20-0.66), had a shorter
      induction to birth interval (mean 13.2 h +/- 7.5 h, women IUFD versus 21.2 +/-
      17.5 h, women fetal anomaly, WMD -8.02 95% CI -11.49 to -4.55) and were more
      likely to give birth within 24 h of the induction process commencing (48/56 women
      IUFD versus 106/143 women fetal anomaly, RR 1.16 95% CI 1.00-1.34). CONCLUSIONS:
      Side-effects increase with increasing dose of misoprostol. Induction following
      intrauterine fetal death is associated with a need for lower doses of misoprostol
      and a shorter induction to birth interval.

PMID- 15730362
TI  - Comparison of transvaginal sonography, saline infusion sonography and
      hysteroscopy in the evaluation of uterine cavity pathologies.
AB  - AIMS: To determine whether performing transvaginal sonography (TVS) and saline
      infusion sonography (SIS) before hysteroscopy could reduce the number of
      diagnostic hysteroscopies performed for the evaluation of uterine cavity
      abnormalities. METHODS: Two hundred and twenty three women with suspected uterine
      cavity abnormalities were prospectively evaluated by TVS, SIS and hysteroscopy,
      and had histological evaluation of the endometrium with hysteroscopic biopsy or
      dilatation and curettage (D&C). One hundred and sixty five patients (74%) were
      premenopausal and 58 patients (26%) were postmenopausal. RESULTS: The positive
      predictive value (PPV) for endometrial polyps was 69% for TVS, 78% for SIS and
      81% for hysteroscopy in premenopausal patients. In the postmenopausal group, TVS
      and SIS could detect only 24% of endometrial polyps, whereas 70% were diagnosed
      by hysteroscopy. The PPV for submucous fibroids was 47% for TVS, 81% for SIS and
      77% for hysteroscopy in the premenopausal group. CONCLUSIONS: In premenopausal
      patients, SIS and hysteroscopy are equally accurate in the diagnosis of
      endometrial polyps and submucous fibroids. Hysteroscopy is the most accurate test
      for polypoid lesions in the postmenopausal group. Performing TVS, SIS and D&C
      could reduce the number of diagnostic hysteroscopies performed for the evaluation
      of uterine cavity abnormalities by 71.5% in premenopausal patients. However, this
      rate decreases to 40% in the postmenopausal group.

PMID- 15730363
TI  - How useful are hospital morbidity data for monitoring conditions occurring in the
      perinatal period?
AB  - BACKGROUND: There is currently no published information on the full range of
      morbid conditions affecting mothers and newborns in Australia. Hospital morbidity
      data collections are a possible source of this information, but have not been
      widely utilised due to concerns about data quality. AIMS: To assess the accuracy
      and reliability of perinatal morbidity reporting to the New South Wales Inpatient
      Statistics Collection (NSW ISC). METHODS: A sample of 1000 records relating to
      500 mothers and 500 newborns were randomly selected from the NSW ISC for the
      financial year 1999-2000 and compared with information obtained from medical
      records. Sensitivities and specificities were calculated for conditions of
      clinical relevance. RESULTS: There was a wide range of sensitivities among the 41
      conditions selected, indicating a variable level of under-enumeration. Only 17
      (41%) had a sensitivity of 80% or more. Sensitivities were more than 95% for
      gestational diabetes, prolonged pregnancy, perineal laceration, single live
      birth, low birth weight, and intracranial haemorrhage. However, numbers are small
      and confidence intervals wide for some of these conditions. Specificities were
      generally high. Neonatal conditions tended to be more accurately reported than
      maternal conditions. The pattern of results was similar to that reported for
      state perinatal data collections. CONCLUSIONS: While hospital administrative data
      are readily available, data quality is a valid concern. However, if the data are
      viewed critically and information on accuracy is available, they can be a useful
      resource for monitoring the health of mothers and babies.

PMID- 15730364
TI  - Alterations in levator ani morphology in elite nulliparous athletes: a pilot
      study.
AB  - BACKGROUND: A difficult vaginal birth is known to be one of the causes of damage
      to the pelvic floor muscles. Prolonged second stage of labour is thought to be
      one of the implicating factors in this damage. If the muscles of the pelvic floor
      were hypertrophied in response to repetitive high impact training, then the
      'suspected phenomenon' of a more difficult childbirth for very athletic women
      might be related to these muscles reducing pelvic floor compliance. AIM: To
      document the muscle morphology of the pelvic floor using magnetic resonance
      imaging (MRI) in a group of nulliparous female athletes and to compare this to
      the findings in a similar group of age-matched nulliparous nonathletic women.
      METHODS: Static Magnetic Resonance (MR) imaging of the pelvic floor was performed
      with particular reference to the muscle morphology of levator ani and
      puborectalis. The cross-sectional area of the urogenital hiatus and the diameter
      of the bony pelvic outlet were also assessed. RESULTS: Significant differences in
      the cross-sectional area and width of the pelvic floor muscles, measured in the
      line of the anal canal, were found between the athletic group and the controls.
      There were no differences found between the two groups in the cross-sectional
      area of the urogenital hiatus, and the adequacy of the pelvic outlet was
      established with reference to normative data. CONCLUSIONS: The differences shown
      in the pelvic floor muscles in the athletes and nonathletes provide a focus for
      further research into this area. This change might influence the function of the
      pelvic floor muscles in this subgroup of women.

PMID- 15730365
TI  - Demographic variables routinely collected at colposcopic examination do not
      predict who will default from conservative management of cervical intraepithelial
      neoplasia I.
AB  - OBJECTIVE: As a result of the low incidence of progression from low grade
      epithelial abnormalities to cervical intraepithelial neoplasia (CIN) 3 or
      cervical cancer, a conservative approach to management is supported, especially
      in young women. Loss to follow-up is a recognised problem with a conservative
      approach however, with women defaulting known to experience higher rates of
      cancer. AIM: To determine if any routinely collected demographic variables could
      predict which Australian women would subsequently default from care having
      initially elected to have conservative management of CIN 1 lesions. METHODS:
      Prospectively collected data was audited on 279 women with a colposcopically
      directed biopsy diagnosis of CIN 1, confirmed on external review, who were
      enroled by their own choice into a conservative management program and monitored
      until a definitive lesion outcome was determined. Women who defaulted from follow
      up and were lost to care providers despite follow-up appointments and reminder
      letters were compared to women who completed follow-up with either lesion
      resolution or progression requiring treatment, to establish if there were any
      demographic variables to predict default from care. RESULTS: Fifty-two (18.5%)
      women subsequently defaulted from follow-up. There were no significant
      differences in age, parity, proportion of women who were pregnant at diagnosis,
      smoking status, immunosuppressed or had a 'human papillomavirus (HPV) effect'
      reported on Pap-smear or colposcopic examination. CONCLUSION: We cannot easily
      identify a subgroup of women who are more likely to default from follow-up of CIN
      1 using routinely collected demographic data. Default from follow-up is a major
      risk with conservative approaches and further research to reduce default rates
      are required.

PMID- 15730366
TI  - Suburethral slingplasty evaluation study in North Queensland, Australia: the
      SUSPEND trial.
AB  - OBJECTIVE: To compare the safety and efficacy of three types of suburethral
      slings for the treatment of urodynamic stress incontinence. METHODS: Following
      ethics approval, 195 (3 x 65) patients with urodynamic stress incontinence were
      randomly assigned to undergo suburethral slingplasty with the Tension-free
      Vaginal Tape (TVT; Gynecare, Ethicon, Somerville, NJ, USA), Intravaginal Sling
      (IVS; Tyco Healthcare, Mansfield, MA, USA), or Suprapubic Arc Sling (SPARC;
      American Medical Systems, Minnetonka, MN, USA). The patients were blinded to the
      type of sling implanted. MAIN OUTCOME MEASURES WERE: (1) operative and short-term
      complications; (2) pre- and postoperative symptomatology; and (3) pre- and
      postoperative urodynamic findings. RESULTS: There was a statistically significant
      increased rate of sling protrusion (13.1% vs. 3.3% and 1.7%; P = 0.04) in the
      SPARC group when compared to TVT and IVS. Otherwise, there were no significant
      differences between the groups with respect to the incidences of other operative
      complications, patients' main subjective outcomes, satisfaction rates, or
      postoperative urodynamic findings. The overall objective stress incontinence cure
      rates were 87.9%, 81.5% and 72.4% for the TVT, IVS, SPARC groups respectively (P
      = 0.11). CONCLUSIONS: All three slings appear quite successful for the treatment
      of stress incontinence. The SPARC tapes showed more sling protrusion
      complications and a trend towards lower objective cure rates; probably as a
      result of the insertion method used in this study which favoured a loose SPARC
      sling placement. The authors recommend that the SPARC slings be left tighter than
      TVT, or for the cough test to be carried out.

PMID- 15730368
TI  - Total versus subtotal hysterectomy: an observational study with one-year follow
      up.
AB  - The aim of this study was to compare total and subtotal abdominal hysterectomy
      for benign indications, with regard to urinary incontinence, postoperative
      complications, quality of life (SF-36), constipation, prolapse, satisfaction with
      sexual life, and pelvic pain at 1-year postoperative. Eighty women chose total
      and 105 women chose subtotal abdominal hysterectomy. No significant differences
      were found between the 2 operation methods in any of the outcome measures at 12
      months. Fourteen women (15%) from the subtotal abdominal hysterectomy group
      experienced vaginal bleeding and three women had their cervix removed.

PMID- 15730367
TI  - Coexistence of verrucous and squamous carcinoma of the vulva.
AB  - AIM: To evaluate the coexistence of verrucous and squamous carcinoma of the vulva
      and to assess the clinical course, survival and rate of recurrent disease of
      these patients. METHODS: The records of 17 patients who were diagnosed with
      verrucous carcinoma of the vulva over a 12-year period were studied
      retrospectively. Presence of genuine verrucous carcinoma or coexistence of
      verrucous and squamous carcinoma of the vulva on vulvar biopsies, results of
      histopathological assessment of final vulva and inguino-femoral node specimens
      and histological evaluation of recurrent disease specimens were the main outcome
      measures. RESULTS: Five of the 17 patients (29.5%) initially underwent radical
      vulvectomy and inguino-femoral lymphadenectomy. Histology of the specimens
      verified the coexistence of verrucous and squamous carcinomas in four of the five
      cases. Twelve women (70.5%) underwent simple vulvectomy for genuine verrucous
      carcinoma; in the final histology, 10 of these women (58.8%) were confirmed as
      having genuine verrucous carcinomas while two (11.7%) were found to have both
      verrucous and squamous carcinomas and were further managed by lymphadenectomy.
      None of our patients died of the disease. Three women (17.5%) presented with
      local relapse of the tumour, and were managed by wide local excision of the
      tumour. CONCLUSIONS: In the present study, 35% of patients with verrucous
      carcinomas of the vulva had coexistent squamous carcinoma. Separation of the
      cases of genuine verrucous carcinoma from coexistent verrucous and squamous
      tumours is based on the establishment of correct diagnosis by a large and deep
      vulvar biopsy as well as the meticulous assessment of the specimen by the
      pathologist. This will result in the decrease of the rate of over- and under
      treatment of these patients.

PMID- 15730369
TI  - Obstetric outcomes among rural Aboriginal Victorians.
AB  - Twenty-eight Aboriginal women and 112 age-matched controls were identified from a
      retrospective chart review of deliveries over a 1-year period in northern
      Victoria. Significantly more Aboriginal women were screened for gestational
      diabetes and met criteria for the diagnosis of gestational diabetes. Overall mode
      of delivery was similar amongst the two groups. Babies born to Aboriginal mothers
      were significantly smaller and less likely to be breast fed than those from the
      non-Aboriginal group.

PMID- 15730370
TI  - Effects of tibolone on the quality of life, anxiety-depression levels and
      cognitive functions in natural menopause: an observational follow-up study.
AB  - The effects of tibolone on the quality of life (QoL), depression-anxiety levels
      and cognitive functions were investigated. Seventeen women received tibolone and
      25 women did not receive any medication. At the end of the 6-month follow-up
      period, the QoL was better in the tibolone group in the area of mental health.
      Disability, anxiety symptoms, menopausal symptoms were significantly reduced in
      this group.

PMID- 15730371
TI  - Suprapubic catheterisation: a retrospective comparison of two insertion systems.
AB  - Abstract This study compares two suprapubic catheter insertion systems available
      for postoperative bladder drainage. We performed retrospective analysis of
      patients who underwent laparoscopic colposuspension and postoperative suprapubic
      catheterisation with either the Bonanno (Becton, Franklin Lakes, NJ, USA) or the
      Lawrence Add-a-Cath (Femcare, Nottingham, UK) mini-Foley catheters (Bard,
      Covington, GA, USA). There were no statistically significant postoperative
      outcome differences between the two catheter groups. We prefer the Add-a-Cath
      mini-Foley suprapubic catheter for its ease of insertion and fixation.

PMID- 15730372
TI  - Role of internal anal sphincter damage in the causation of idiopathic faecal
      incontinence: a prospective study.
AB  - This prospective study aimed to examine the relationship between internal anal
      sphincter (IAS) damage and 'idiopathic' faecal incontinence (FI) in 50
      consecutive patients, using endoanal ultrasound examination. The external anal
      sphincter (EAS) was intact on direct and ultrasonic assessment in all patients.
      IAS damage was defined as complete rupture or attenuation, less than 2 mm
      thickness in some part of the sphincter. Complete rupture was found in one
      patient and damage in a further 17 (total 36%). All three nulliparous patients
      had normal IAS and EAS. IAS damage was only minimally associated with
      'idiopathic' FI, suggesting IAS per se is unlikely to be a direct cause of FI in
      the 'idiopathic' group of FI patients. Its role might be analogous to the
      periurethral striated horse-shoe shape muscle in the urethra, which is thought to
      act as a mucosal sealant.

PMID- 15730373
TI  - Gynaecology meets neurology: paraneoplastic cerebellar degeneration.

PMID- 15730374
TI  - Non-puerperal uterine inversion caused by uterine sarcoma.

PMID- 15730375
TI  - Giant neurofibroma of the vulva.

PMID- 15730376
TI  - Chorangioma with atypical trophoblastic proliferation.

PMID- 15730378
TI  - Uretero-uterine fistula following dilatation and curettage.

PMID- 15730377
TI  - Primary uterine lymphoma: case report and literature review.

PMID- 15730379
TI  - Diabetes mellitus as the only manifestation of occult phaeochromocytoma prior to
      acute haemorrhage in pregnancy.

PMID- 15730380
TI  - B-Lynch uterine compression suture for postpartum haemorrhage due to placenta
      praevia accreta.

PMID- 15730381
TI  - Vaginal leiomyoma developing after hysterectomy - case report and literature
      review.

PMID- 15730383
TI  - Targeting the dendritic cell: the key to immunotherapy in cancer?

PMID- 15730382
TI  - C1 inhibitor deficiency: consensus document.
AB  - We present a consensus document on the diagnosis and management of C1 inhibitor
      deficiency, a syndrome characterized clinically by recurrent episodes of angio
      oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1
      inhibitor function is reduced due to impaired transcription or production of non
      functional protein. The diagnosis is confirmed by the presence of a low serum C4
      and absent or greatly reduced C1 inhibitor level or function. The condition can
      cause fatal laryngeal oedema and features indistinguishable from gastrointestinal
      tract obstruction. Attacks can be precipitated by trauma, infection and other
      stimulants. Treatment is graded according to response and the clinical site of
      swelling. Acute treatment for severe attack is by infusion of C1 inhibitor
      concentrate and for minor attack attenuated androgens and/or tranexamic acid.
      Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There
      are a number of new products in trial, including genetically engineered C1
      esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist.
      Individual sections provide special advice with respect to diagnosis, management
      (prophylaxis and emergency care), special situations (childhood, pregnancy,
      contraception, travel and dental care) and service specification.

PMID- 15730384
TI  - Low dose chronic Schistosoma mansoni infection increases susceptibility to
      Mycobacterium bovis BCG infection in mice.
AB  - The incidence of mycobacterial diseases is high and the efficacy of Bacillus
      Calmette Guerin (BCG) is low in most areas of the world where chronic worm
      infections are common. However, if and how concurrent worm infections could
      affect immunity to mycobacterial infections has not been elucidated. In this
      study we investigated whether infection of mice with Schistosoma mansoni could
      affect the ability of the animals to control Mycobacterium bovis BCG infection
      and the immune response to mycobacterial antigens. BALB/c mice subclinically
      infected with S. mansoni were challenged with M. bovis BCG via the intravenous
      route. The ability of the animals to contain the replication of M. bovis BCG in
      their organs, lung pathology as well as the in vitro mycobacterial and worm
      antigen induced immune responses were evaluated. The results showed that S.
      mansoni coinfected mice had significantly higher levels of BCG bacilli in their
      organs and sustained greater lung pathology compared to Schistosoma uninfected
      controls. Moreover, Schistosoma infected mice show depressed mycobacterial
      antigen specific Th1 type responses. This is an indication that chronic worm
      infection could affect resistance/susceptibility to mycobacterial infections by
      impairing mycobacteria antigen specific Th1 type responses. This finding is
      potentially important in the control of TB in helminth endemic parts of the
      world.

PMID- 15730385
TI  - TNF-alpha mediates the development of anaemia in a murine Trypanosoma brucei
      rhodesiense infection, but not the anaemia associated with a murine Trypanosoma
      congolense infection.
AB  - Development of anaemia in inflammatory diseases is cytokine-mediated.
      Specifically, the levels of tumour necrosis factor-alpha (TNF-alpha), produced by
      activated macrophages, are correlated with severity of disease and anaemia in
      infections and chronic disease. In African trypanosomiasis, anaemia develops very
      early in infection around the time when parasites become detectable in the blood.
      Since the anaemia persists after the first waves of parasitaemia when low numbers
      of trypanosomes are circulating in the blood, it is generally assumed that
      anaemia is not directly induced by a parasite factor, but might be cytokine
      mediated, as in other cases of anaemia accompanying inflammation. To clarify the
      role of TNF-alpha in the development of anaemia, blood parameters of wild type
      (TNF-alpha+/+), TNF-alpha-null (TNF-alpha-/-) and TNF-alpha-hemizygous (TNF-alpha
      /+) trypanotolerant mice were compared during infections with the cattle parasite
      Trypanosoma congolense. No differences in PCV, erythrocyte numbers or haemoglobin
      were observed between TNF-alpha-deficient and wild type mice, suggesting that the
      decrease in erythrocytes was not mediated by TNF-alpha. Erythropoetin (EPO)
      levels increased during infection and no significant differences in EPO levels
      were observed between the three mouse strains. In contrast, during an infection
      with the human pathogen Trypanosoma brucei rhodesiense, the number of red blood
      cells in TNF-alpha-deficient mice remained significantly higher than in the wild
      type mice. These data suggest that more than one mechanism promotes the
      development of anaemia associated with trypanosomiasis.

PMID- 15730386
TI  - Vasoactive intestinal peptide impairs leucocyte migration but fails to modify
      experimental murine colitis.
AB  - Inflammatory bowel diseases are chronic inflammatory disorders of the
      gastrointestinal tract. Vasoactive intestinal peptide (VIP) is a neuropeptide
      with known anti-inflammatory activity. We have demonstrated previously that
      administration of VIP inhibits leucocyte migration in a murine model of delayed
      type hypersensitivity, and anti-inflammatory efficacy is supported by other
      studies. The aim of this study was to investigate the VIP effects in a murine
      model of intestinal inflammation. Colitis was induced in BALB/c mice by a 2.5 mg
      enema of 2,4,6-trinitrobenzenesulphonic acid (TNBS) and the mice were killed on
      day 7. Mice were administered either a 3-day (therapeutic) or 7-day
      (prophylactic) constant infusion of VIP by subcutaneously implanted mini-osmotic
      pumps, or intraperitoneal (i.p.) injection of VIP on alternate days over 7 days.
      Clinical disease scores, weight changes, histopathology of colon tissues, plasma
      VIP levels, cytokine levels and chemotaxis of peripheral blood mononuclear cells
      were evaluated. After administration of TNBS, mice quickly developed severe
      colitis accompanied by dramatic body weight loss (20% by day 6) and high
      mortality (30%). Prophylactic treatment using high-dose VIP abrogated leucocyte
      chemotaxis; however, it failed to ameliorate the weight loss and mortality.
      Moreover, VIP delivered either by constant infusion or i.p. failed to modify the
      clinical, histological or cytokine markers of disease. Our studies show that,
      despite an ability to inhibit chemokine-induced chemotaxis of mononuclear cells,
      VIP was unable to modulate TNBS-induced colitis. This contrasts with the efficacy
      of VIP in models of mild inflammatory disease and suggests that VIP is unlikely
      to provide a useful model for novel anti-IBD therapy.

PMID- 15730387
TI  - Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1
      and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis.
AB  - Although enhanced lymphocyte trafficking is associated with colitis formation,
      little information about its regulation is available. The aim of this study was
      to examine how the murine liver and activation-regulated chemokine (mLARC/CCL20)
      contributes to lymphocyte recruitment in concert with vascular adhesion molecules
      in murine chronic experimental colitis. T and B lymphocytes isolated from the
      spleen were fluorescence-labelled and administered to recipient mice. Lymphocyte
      adhesion to microvessels of the colonic mucosa and submucosa was observed with an
      intravital microscope. To induce colitis, the mice received two cycles of
      treatment with 2% dextran sodium sulphate (DSS). In some of the experiments
      antibodies against the adhesion molecules or anti-mLARC/CCL20 were administered,
      or CC chemokine receptor 6 (CCR6) of the lymphocytes was desensitized with excess
      amounts of mLARC/CCL20. Significant increases in T and B cell adhesion to the
      microvessels of the DSS-treated mucosa and submucosa were observed. In chronic
      colitis, the accumulation of lymphocytes was significantly inhibited by anti
      mucosal addressin cell adhesion molecule (MAdCAM)-1 mAb, but not by anti-vascular
      cell adhesion molecule-1. In DSS-treated colonic tissue, the expression of
      mLARC/CCL20 was significantly increased, the blocking of mLARC/CCL20 by
      monoclonal antibody or the desensitization of CCR6 with mLARC/CCL20 significantly
      attenuated the DSS-induced T and B cell accumulation. However, the combination of
      blocking CCR6 with MAdCAM-1 did not further inhibit these accumulations. These
      results suggest that in chronic DSS-induced colitis, both MAdCAM-1 and
      mLARC/CCL20 may play important roles in T and B lymphocyte adhesion in the
      inflamed colon under flow conditions.

PMID- 15730388
TI  - Plasminogen activator inhibitor-1 is elevated, but not essential, in the
      development of bleomycin-induced murine scleroderma.
AB  - Accumulative data have demonstrated that plasminogen activator inhibitor-1 (PAI
      1) plays an important role in the extracellular matrix metabolism; however, the
      involvement of PAI-1 in scleroderma has not been fully elucidated. In this study,
      we investigated the role of PAI-1 in bleomycin-induced murine scleroderma. 100
      microg of bleomycin was injected subcutaneously to the back skin of C3H/HeJ mice
      on alternate day for 4 weeks. Histopathological findings revealed that PAI-1 was
      positive in macrophage-like cells and fibroblastic cells in the dermis, in
      parallel with the induction of dermal sclerosis. PAI-1 mRNA expression in the
      whole skin was up-regulated at 1 and 4 weeks. The production of active PAI-1
      protein in the lesional skin was significantly increased 3 and 4 weeks after
      bleomycin treatment. Next, we examined whether dermal sclerosis is induced by
      bleomycin in PAI-1-deficient (PAI-1-/-) mice. 10 microg of bleomycin was
      subcutaneously injected to PAI-1-/- and wild type (WT) mice 5 days per week for 4
      weeks. Histological examination revealed that dermal sclerosis was similarly
      induced even in PAI-1-/- as well as WT mice. Dermal thickness and collagen
      contents in the skin were significantly increased by bleomycin injection in both
      PAI-1-/- and WT mice, and the rate of increase was similar. These data suggest
      that PAI-1 plays an important role, possibly via TGF-beta pathway activation.
      However, the fact that PAI-1 deficiency did not ameliorate skin sclerosis suggest
      that PAI-1 is not the essential factor in the development of bleomycin-induced
      scleroderma, and more complex biochemical effects other than PA/plasmin system
      are greatly suspected.

PMID- 15730389
TI  - Rituxan (anti-CD20 antibody)-induced translocation of CD20 into lipid rafts is
      crucial for calcium influx and apoptosis.
AB  - Rituxan, a chimeric anti-CD20 antibody, is the first antibody approved for
      immunotherapy in non-Hodgkin's B-cell lymphoma and other B-cell
      lymphoproliferative disorders. Additionally, efficacy of Rituxan treatment has
      been reported in nonmalignant autoimmune diseases such as rheumatoid arthritis.
      Crosslinking of CD20 molecules by Rituxan induces therapeutic B-cell depletion.
      CD20 is a B-lymphocyte specific integral membrane protein, proposed to function
      as a store-operated calcium channel, which is activated upon receptor-stimulated
      calcium depletion of intracellular stores. Crosslinking of CD20 by antibodies has
      been reported to induce a redistribution of CD20 molecules to specialized
      microdomains at the plasma membrane known as lipid rafts. Here, we report that in
      the absence of Rituxan, CD20 exhibits a low affinity to lipid rafts. However,
      binding of Rituxan significantly increases the affinity of CD20 for lipid rafts
      resulting in its redistribution to a fraction resistant to Triton X-100
      solubilization. Furthermore, we demonstrate that disturbing the raft integrity by
      cholesterol extraction results in dissociation of CD20 from a Triton X-100
      resistant fraction followed by complete inhibition of Rituxan-induced calcium
      entry and apoptosis. The integrity of lipid rafts seems to play a crucial role
      for CD20-induced caspase activation. These data show, for the first time, that
      Rituxan-induced translocation of CD20 to lipid rafts is important for increased
      intracellular Ca(2+) levels and downstream apoptotic signalling.

PMID- 15730390
TI  - Immunostimulating activities of the novel peptidomimetic L-glutamyl-histamine.
AB  - An original representative of histamine-containing peptidomimetics L-glutamyl
      histamine (L-Glu-Hist) was synthesized and characterized as a cytokine mimic
      leading to cellular responses of improved specificity. The energy-minimized 3-D
      conformations of L-Glu-Hist derived from its chemical structure resulted in
      stabilization for Fe(2+) chelating complexes. L-Glu-Hist accelerated the decrease
      of ferrous iron in the ferrous sulphate solution in a concentration-dependent
      mode and showed the ferroxidase-like activity at concentrations less than 3 mm in
      the phenanthroline assay, whereas in the concentration range 3-20 mm L-Glu-Hist
      restricted the availability of Fe(2+) to phenanthroline due to binding of ferrous
      ions in chelating complexes. L-Glu-Hist showed a stimulatory effect on
      phosphatidylcholine liposomal peroxidation (LPO) catalysed by the superoxide
      anion radical (O(2) (*))-generating system (Fe(2+)+ ascorbate) at low (less or
      about 1 mm) L-Glu-Hist concentrations and both revealed the inhibitory effect on
      LPO in this system of high ( approximately 10 mm) L-Glu-Hist concentration. L-Glu
      Hist released O(2) (*) in concentrations which stimulated [(3)H]-thymidine
      incorporation into DNA and proliferation of mouse spleen lymphocytes and
      mononuclear cells from human blood. The structural peptide-like analogues of L
      Glu-Hist such as L-Glu-Trp, carcinine (beta-alanylhistamine), but not L-Pro-Glu
      Trp were active in stimulating thymidine incorporation and in inducing
      proliferation of mononuclear cells compared to mitogen concanavalin A at doses
      2.5-25.0 microg/ml. Our data provide evidence that L-Glu-Hist may act as a very
      fast and sensitive trigger for lymphocyte proliferation and immunoregulation.

PMID- 15730391
TI  - Ex vivo induction of viral antigen-specific CD8 T cell responses using mRNA
      electroporated CD40-activated B cells.
AB  - Cell-based immunotherapy, in which antigen-loaded antigen-presenting cells (APC)
      are used to elicit T cell responses, has become part of the search for
      alternative cancer and infectious disease treatments. Here, we report on the
      feasibility of using mRNA-electroporated CD40-activated B cells (CD40-B cells) as
      alternative APC for the ex vivo induction of antigen-specific CD8(+) T cell
      responses. The potential of CD40-B cells as APC is reflected in their phenotypic
      analysis, showing a polyclonal, strongly activated B cell population with high
      expression of MHC and co-stimulatory molecules. Flow cytometric analysis of EGFP
      expression 24 h after EGFP mRNA-electroporation showed that CD40-B cells can be
      RNA transfected with high gene transfer efficiency. No difference in transfection
      efficiency or postelectroporation viability was observed between CD40-B cells and
      monocyte-derived dendritic cells (DC). Our first series of experiments show
      clearly that peptide-pulsed CD40-B cells are able to (re)activate both CD8+ and
      CD4(+) T cells against influenza and cytomegalovirus (CMV) antigens. To
      demonstrate the ability of viral antigen mRNA-electroporated CD40-B cells to
      induce virus-specific CD8+ T cell responses, these antigen-loaded cells were co
      cultured in vitro with autologous peripheral blood mononuclear cells (PBMC) for 7
      days followed by analysis of T cell antigen-specificity. These experiments show
      that CD40-B cells electroporated with influenza M1 mRNA or with CMV pp65 mRNA are
      able to activate antigen-specific interferon (IFN)-gamma-producing CD8(+) T
      cells. These findings demonstrate that mRNA-electroporated CD40-B cells can be
      used as alternative APC for the induction of antigen-specific (memory) CD8(+) T
      cell responses, which might overcome some of the drawbacks inherent to DC
      immunotherapy protocols.

PMID- 15730392
TI  - Mature dendritic cells differentiated in the presence of interferon-beta and
      interleukin-3 prime functional antigen-specific CD8 T cells.
AB  - Dendritic cell (DC)-based immunization represents a promising approach for the
      immunotherapy of cancer. The optimal conditions required to prepare DCs remain to
      be defined. Monocytes incubated in the presence of interferon (IFN)-beta and
      interleukin (IL)-3 give rise to a distinct type of DCs (IFN-beta/IL-3 DCs) that
      are particularly efficient at eliciting IFN-gamma and IL-5 production by
      allogeneic helper T cells. We assessed the capacity of this new type of DCs to
      prime antigen-specific naive CD8(+) T cells and compared them to the conventional
      DCs differentiated in the presence of granulocyte-macrophage colony stimulating
      factor (GM-CSF) and IL-4 (GM-CSF/IL-4 DCs). We demonstrate that IFN-beta/IL-3 DCs
      matured by TLR3 or CD40 ligation efficiently prime Melan-A(26-35)-specific CD8(+)
      T cells in vitro, at a similar level as GM-CSF/IL-4 DCs. Activated antigen
      specific CD8(+) T cells produced IFN-gamma and displayed potent cytotoxic
      activity against peptide-pulsed target cells. Expansion of CD8(+) T cell numbers
      was generally higher following priming with CD40-L than with polyinosinic
      polycytidylic acid (poly I:C) matured DCs. Cytolytic activity was induced by both
      maturing agents. These data indicate that IFN-beta/IL-3 DCs represent a promising
      cell population for the immunotherapy of cancer.

PMID- 15730393
TI  - Engagement of human monocyte-derived dendritic cells into interleukin (IL)-12
      producers by IL-1beta + interferon (IFN)-gamma.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells and can induce tumour-
      or pathogen-specific T cell responses. For adoptive immunotherapy purposes,
      immature DCs can be generated from adherent monocytes using granulocyte
      macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4, and further
      maturation is usually achieved by incubation with tumour necrosis factor (TNF)
      alpha. However, TNF-alpha-stimulated DCs produce low levels of IL-12. In this
      study, we compared the effects of TNF-alpha, interferon (IFN)-gamma, IL-1beta or
      IFN-gamma + IL-1beta on the phenotypic and functional maturation of DCs. Our
      results show that IFN-gamma, but not IL-1beta, augmented the surface expression
      of CD80, CD83 and CD86 molecules without inducing IL-12 production from DCs.
      However, IL-1beta, but not IFN-gamma, induced IL-12 p40 production by DCs without
      enhancing phenotypic maturation. When combined, IFN-gamma + IL-1beta treatment
      profoundly up-regulated the expression of CD80, CD83, CD86 and major
      histocompatibility complex (MHC) class II antigens. Furthermore, IFN-gamma + IL
      1beta-treated DCs produced larger amounts of IL-12 and induced stronger T cell
      proliferation and IFN-gamma secretion in primary allogeneic mixed lymphocyte
      reaction (MLR) than did TNF-alpha-treated DCs. Our results show that IFN-gamma +
      IL-1beta induced human monocyte-derived DCs to differentiate into Th1-prone
      mature DCs.

PMID- 15730394
TI  - Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative
      responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in
      Guinea-Bissau.
AB  - Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative
      responses were determined in cultures of peripheral blood mononuclear cells from
      HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative
      controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative
      responses were detected in both groups compared to HIV-negative controls (healthy
      HIV-uninfected individuals without known exposure to an HIV-infected person);
      five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2
      infected individuals had stimulation indexes >2, compared to one out of 49 of the
      HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed
      uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to
      amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people
      reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high
      degree of HIV-2-specific T helper cell activity, as measured by lymphocyte
      proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2
      infected subjects. These immune responses could be important for resistance to
      the infection and for the control of established infection and, thus, play a role
      in the lower transmission and progression of HIV-2 compared to HIV-1.

PMID- 15730395
TI  - Clinical investigation: increased serum stromal derived factor 1 alpha levels in
      pulmonary tuberculosis.
AB  - Pulmonary tuberculosis, a granulomatous disease, has few serological markers for
      its activity. Recently, an increased plasma level of stromal derived factor 1
      alpha (SDF-1alpha), which can induce strong chemotaxis of cells through its
      receptor CXCR4, was detected in patients with tuberculosis. In this study we
      investigated serum SDF-1alpha levels and CXCR4 expression on peripheral blood
      mononuclear cells (PBMCs). Fifty-five active tuberculosis patients, 30 resolved
      tuberculosis patients, 27 acute bronchitis patients and 8 healthy volunteers were
      examined. Histological expression of SDF-1alpha in the tuberculosis lesion and
      CXCR4 expression of PBMCs were also analysed. Serum SDF-1alpha levels in active
      tuberculosis patients were significantly higher than other groups. The
      sensitivity and specificity for the diagnosis of active tuberculosis was 88.5%
      and 85.3% (cutoff value = 650 pg/ml), respectively. CXCR4 expression levels on
      PBMCs showed a significant negative correlation with serum SDF-1alpha levels.
      Inflammatory cells including multinuclear giant cells in the lesion expressed SDF
      1alpha. Measurement of serum SDF-1alpha could be a useful screening marker for
      the identification of active pulmonary tuberuculosis. We propose that interaction
      of SDF-1alpha and CXCR4 might be involved in the pathogenesis of pulmonary
      tuberculosis.

PMID- 15730396
TI  - Mononuclear cells from patients recovered from cutaneous leishmaniasis respond to
      Leishmania major amastigote class I nuclease with a predominant Th1-like
      response.
AB  - The Leishmania major amastigote class I nuclease (LmaCIN) is a developmentally
      regulated protein that is highly expressed in the amastigote stage of L. major.
      This protein is homologous to the P4 nuclease of L. pifanoi, which has been shown
      to induce protective immune response in a murine model. To evaluate LmaCIN as a
      potential human vaccine candidate, cellular immune responses to recombinant
      LmaCIN were examined in individuals recovered from Old World cutaneous
      leishmaniasis. Peripheral blood mononuclear cells (PBMC) from patients recovered
      from L. major infection were cultured either with recombinant LmaCIN or
      autoclaved L. major (ALM) as control. rLmaCIN induced significant proliferation
      of PBMC from 90% of recovered patients. Phenotypic analysis of proliferating
      cells showed that CD8(+) cells were the predominant cell type proliferating in
      response to rLmaC1N. Screening of culture supernatants for cytokines showed that
      rLmaCIN induced high levels of interferon (IFN)-gamma (mean +/- s.e.m.: 1398 +/-
      179 pg/ml) associated with little interleukin (IL)-10 and little or no IL-5
      production. These findings show that LmaCIN is immunogenic in humans during L.
      major infection and that it can elicit immunological responses relevant to
      immunoprophylaxis of leishmaniasis.

PMID- 15730397
TI  - Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, in periodontal
      diseased tissue.
AB  - The regulatory role of chemokines and chemokine receptors on specific leucocyte
      recruitment into periodontal diseased tissue is poorly characterized. We observed
      that leucocytes infiltrating inflamed gingival tissue expressed marked levels of
      CX3CR1. In periodontal diseased tissue, the expression of fractalkine and CX3CR1
      mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) and
      further, fractalkine was distributed mainly on endothelial cells, as shown by
      immunohistochemistry. Moreover, we can detect CX3CR1-expressing cells infiltrated
      in periodontal diseased tissue by immunohistochemical staining. Furthermore,
      fractalkine production by human umbilical vein endothelial cells (HUVEC) was up
      regulated by pathogen-associated molecular patterns (PAMPs), including
      Porphyromonas gingivalis lipopolysaccharide (LPS). Thus, these findings suggested
      that CX3CR1 and the corresponding chemokine, fractalkine may have an important
      regulatory role on specific leucocyte migration into inflamed periodontal tissue.

PMID- 15730398
TI  - Characterization of human peritoneal dendritic cell precursors and their
      involvement in peritonitis.
AB  - Scattered evidence suggests that the human peritoneal cavity contains cells of
      the dendritic cell (DC) lineage but their characterization is missing. Here, we
      report that the peritoneal cavity of normal subjects and of stable patients on
      peritoneal dialysis (PD) contains a population of CD14(+) cells that can
      differentiate into DCs or macrophages. Within this pool, we characterized a
      CD14(+)CD4(+) cell subset (2.2% of the peritoneal cells) fulfilling the
      definition of myeloid DC precursors or pre-DC1 cells. These cells expressed high
      levels of HLA-DR, CD13, CD33, and CD86, and low levels of CD40, CD80, CD83,
      CD123, CD209, TLR-2 and TLR-4. These cells retained CD14 expression until late
      stages of differentiation, despite concomitant up-regulation of DC-SIGN (CD209),
      CD1a, CD80 and CD40. Peritoneal pre-DC1 cells had endocytic capacity that was
      down-regulated upon LPS/IFN-gamma stimulation, were more potent allo-stimulators
      than peritoneal CD14(+)CD4(-/lo) cells and monocyte-derived macrophages, and
      induced Th1 cytokine responses. More importantly, the number of peritoneal pre
      DC1 cells increased during PD-associated peritonitis, with a different profile
      for Gram positive and Gram negative peritonitis, suggesting that these cells
      participate in the induction of peritoneal adaptive immune responses, and may be
      responsible for the bias towards Th1 responses during peritonitis.

PMID- 15730399
TI  - Altered expression of type I insulin-like growth factor receptor in Crohn's
      disease.
AB  - The fibrotic and antiapoptotic effects of insulin-like growth factors (IGF) are
      mediated by type I IGF receptor (IGF-1R). IGFs could play a role in intestinal
      stricturing and in the maintenance of inflammation in Crohn's disease (CD). We
      aimed to describe IGF-1R expression in CD intestinal lesions, to compare it to
      other intestinal inflammatory diseases and to correlate it with fibrosis and
      apoptosis. IGF-1R expression and apoptosis (active caspase-3) were studied by
      immunohistochemistry. Surgical intestinal specimens [17 CD, nine controls, six
      diverticulitis and four ulcerative colitis (UC)] were used. IGF-1R was expressed
      transmurally mainly by inflammatory cells (IC) and smooth muscle cells, both in
      diseased intestine and controls. IGF-1R positive IC were increased in the mucosa
      and the submucosa of CD (P < 0.007), and in involved areas compared to uninvolved
      areas (P = 0.03). In UC, the number of IGF-1R positive IC was only increased in
      the mucosa, and was not different from controls in the submucosa. In
      diverticulitis, the number of IGF-1R positive IC did not differ from controls. In
      CD submucosa, IGF-1R expression in IC was inversely correlated with apoptosis in
      uninvolved areas (P = 0.01). Expression of IGF-1R in submucosal fibroblast-like
      cells, subserosal adipocytes and hypertrophic nervous plexi was specific for CD.
      We have shown a transmural altered expression of IGF-1R in CD. This may suggest a
      role for IGF-1R in the maintenance of chronic inflammation and stricture
      formation in CD.

PMID- 15730401
TI  - IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to
      citrullinated fibrin.
AB  - In the rheumatoid synovium, deiminated ('citrullinated') forms of fibrin are the
      major targets of IgG autoantibodies to citrullinated proteins (ACPA), the most
      specific serological markers of rheumatoid arthritis (RA). To further the
      characterization of ACPA, we determined their subclass distribution. From a
      previously validated highly sensitive and specific enzyme-linked immunosorbent
      assay (ELISA) onto in vitro deiminated human fibrinogen - antihuman fibrin(ogen)
      autoantibodies (AhFibA)-ELISA - we derived and calibrated four ELISAs, using
      monoclonal antibodies to each of the four IgG subclasses, to determine the
      proportions of AhFibA subclasses in the sera. A series of 186 serum samples from
      RA patients was analysed. All AhFibA-positive sera contained IgG1-AhFibA, which
      reached the highest titres and accounted for more than 80% of AhFibA in three
      quarters of the sera. One or two other subclasses were associated with IgG1 in
      39% of the sera, IgG4-AhFibA being observed much more frequently and at higher
      titres than IgG3- or IgG2-AhFibA. IgG1 alone or IgG(1 + 4)-AhFibA were the AhFibA
      subclass profiles found in more than 80% of patients. AhFibA are mainly IgG1 and,
      to a lesser extent, IgG4. Such IgG subclass profiles may influence the effector
      phases of the immunological conflict between ACPA and deiminated fibrin that
      takes place specifically in the rheumatoid synovium and therefore may play a
      critical role in the self-maintenance of rheumatoid inflammation.

PMID- 15730400
TI  - Altered CD46-mediated T cell co-stimulation in haemodialysis patients.
AB  - While most of our understanding of immune dysfunction in dialysis patients
      involves alterations in CD28-CD80/86 signalling, nothing is known of CD46
      mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to
      CD46 and complement activation occurs during haemodialysis (HD), we addressed
      whether CD46-mediated T cell activation is altered in HD (n = 9), peritoneal
      dialysis (PD) (n = 10) and predialysis patients (n = 8) compared to healthy
      controls (HC) (n = 8). T cell surface markers, T cell proliferation and
      interleukin (IL)-10 production were studied in CD4(+)T cells. In addition, CD46
      splice-variants and IL-10 promoter gene polymorphisms were studied by reverse
      transcription (RT) or amplification refractory mutation system-polymerase chain
      reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the
      stage of renal insufficiency or dialysis modality, a significant increase in the
      percentage of CD25 positivity in naive CD4(+)T cells was found (64% +/- 21%versus
      23% +/- 18%, P < 0.001). Lymphocytes of HD patients proliferated in greater
      numbers and produced more IL-10 after co-stimulation with anti-CD46 than after co
      stimulation with anti-CD28. This was also found in CD4(+)T cells of PD patients,
      albeit to a lesser extent. In contrast, with T cells of predialysis patients and
      of HC, co-stimulation via CD28 was more efficient. The observed alterations in T
      cell proliferation and IL-10 production were associated neither with CD46 splice
      variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients
      show an increased response on CD46 co-stimulation. These data suggest that
      ongoing complement activation in HD patients may lead to alterations in acquired
      immunity.

PMID- 15730402
TI  - Alpha4beta1 and alpha4beta7 CD4 T cell numbers increase and CLA CD4 T cell
      numbers decrease in systemic sclerosis.
AB  - We studied the expression of adhesion molecules affecting recirculation and
      homing on peripheral blood CD4(+) T cells of patients with systemic sclerosis
      (SSc), in order to evaluate whether the distribution of tissue targeted subsets
      could reflect the participation of internal organs or the extent of cutaneous
      involvement [i.e. limited cutaneous (lc) and diffuse cutaneous (dc)]. Peripheral
      blood mononuclear cells (PBMC) from 51 patients with SSc and 19 sex- and age
      matched controls were investigated by cytofluorimetric analysis for lymphocyte
      subpopulations carrying the following surface molecules: CD3, CD4, CLA,
      alpha4beta7 and alpha4beta1. Standard routine biochemistry and clinical
      examinations were also performed in all patients. We found that both
      alpha4beta1(+) and alpha4beta7(+) cells within the CD4(+) T cell population were
      significantly increased, while CLA(+) CD4(+) T cells were significantly reduced
      in SSc, compared to healthy donors. Significantly lower absolute numbers of
      alpha4beta7(+) cells were found in lc- compared to dc-SSc. Patients with
      oesophageal involvement had high numbers of alpha4beta7(+) cells, while those
      with nephritis also showed low levels of CLA(+) cells. Lung involvement was
      related directly to alpha4beta1(+) cell numbers and inversely to alpha4beta7(+)
      CD4 cell numbers. Taken together, our findings demonstrate that distinct CD4(+) T
      cell populations with selective homing properties show changes from normal
      distribution in SSc, and such changes are related to clinical expression and
      organ involvement in the course of the disease.

PMID- 15730403
TI  - Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of
      Epstein-Barr virus nuclear antigen-2 in sera from patients with systemic
      connective tissue diseases and from a subgroup of Sjogren's syndrome patients
      with pulmonary involvements.
AB  - Associations of Epstein-Barr virus (EBV) and autoimmune diseases have been
      hypothesized. We have analysed IgG antibodies to EBV nuclear antigen (EBNA)-2 in
      sera from Japanese patients with autoimmune systemic connective tissue diseases
      (CTD), exemplified by systemic lupus erythematosus (SLE), primary Sjogren's
      syndrome (SS), rheumatoid arthritis (RA), systemic sclerosis (SSc) and secondary
      SS (classical CTDs complicated with SS). An enzyme-linked immunosorbent assay
      (ELISA) which uses glutathione-S-transferase polypeptides fused to EBV nuclear
      antigen (EBNA)-2 and EBNA-1 was developed. Ratios of IgG antibody reactivity to
      whole IgG concentrations of sera were calculated to normalize EBNA-2 and EBNA-1
      antibody levels to the hypergammaglobulinaemia that occurs in CTD. The ELISA
      optical density OD(450) readings of IgG antibodies to both the amino-terminal aa
      1-116 of EBNA-2 and carboxyl-terminal aa 451-641 of EBNA-1 were elevated
      significantly in patients with SLE, primary SS, RA, SSc and secondary SS when
      compared to EBNA-1. The OD readings were divided by serum IgG concentrations to
      normalize for the hypergammaglobulinaemia. The specific levels of IgG antibodies
      to the amino-terminal region of EBNA-2 were elevated in patients with SLE,
      primary SS or RA, as well as those with secondary SS complicated with SLE or RA.
      The EBNA-2 amino-terminal region contains a polyproline tract and a proline-rich
      sequence and has considerable amino acid sequence homology with many cellular
      proline-rich proteins. High ratios of EBNA-2 aa 1-116 to EBNA-1 aa 451-641 IgG
      antibody levels which probably suggest reactivation of EBV latent infection were
      associated significantly with pulmonary involvement in SS patients. These results
      are consistent with the hypothesis that the sequence similarity between the amino
      terminal region of EBNA-2 and proline-rich cellular proteins is associated with
      pathogenesis in a subpopulation of CTD patients, possibly by the molecular
      mimicry-epitope shift mechanism.

PMID- 15730404
TI  - Anti-endothelial cell antibodies (AECA) in patients with propylthiouracil (PTU)
      induced ANCA positive vasculitis are associated with disease activity.
AB  - Increasing evidence has demonstrated that propylthiouracil (PTU) could induce
      ANCA positive vasculitis. However, our previous work has suggested that only one
      fifth of the PTU-induced ANCA positive patients had clinical vasculitis and so
      the mechanism is not clear. Anti-endothelial cell antibodies (AECA) have been
      implicated in the pathogenesis of various vasculitides, including primary ANCA
      positive systemic vasculitis. The purpose of this study is to investigate the
      prevalence of AECA and their possible role in the pathogenesis of patients with
      PTU-induced ANCA positive vasculitis. Sera from 11 patients with PTU-induced ANCA
      positive vasculitis at both active and quiescent phases, and sera from 10
      patients with PTU-induced ANCA but without clinical vasculitis, were studied.
      Sera from 30 healthy blood donors were collected as normal controls. Soluble
      proteins from 1% Triton-100 extracted in vitro cultured human umbilical vein
      endothelial cells were used as antigens and an immunoblotting technique was
      performed to determine the presence of AECA, and their specific target antigens
      were identified. In patients with PTU-induced ANCA positive vasculitis, 10 of the
      11 patients in an active phase of disease were serum IgG-AECA positive and six
      protein bands of endothelial antigens could be blotted (61 kD, 69 kD, 77 kD, 85
      kD, 91 kD and 97 kD). However, in the quiescent phase, seven of the 10 positive
      sera turned negative. None of the ANCA positive but vasculitis negative patients
      or normal controls were AECA positive. In conclusion, AECA could be found in sera
      from patients with PTU-induced ANCA positive vasculitis and were associated more
      closely with vasculitic disease activity.

PMID- 15730405
TI  - Imbalance in the production between vascular endothelial growth factor and
      endostatin in Kawasaki disease.
AB  - To investigate whether an imbalance exists in the production between angiogenic
      and antiangiogenic growth factors in patients with Kawasaki disease (KD), we
      measured the serum levels of vascular endothelial growth factor (VEGF) and
      endostatin (ES) in 35 patients with KD, 15 patients with acute febrile diseases
      (disease controls) and 15 healthy children. KD patients had significantly higher
      VEGF levels and lower ES levels (P < 0.01) in the acute and subacute phases than
      the disease control and healthy children. KD patients with coronary artery
      lesions (CAL, n = 10) had significantly higher VEGF levels and lower ES levels (P
      < 0.05) in the subacute and convalescent phases than those without CAL (n = 25).
      The ratios of VEGF/ES in sera of KD patients with CAL were significantly higher
      (P < 0.05) in the acute and convalescent phases compared to those without CAL.
      Furthermore, the occurrence of CAL significantly correlated with the VEGF/ES
      ratio above 10 x 10(-3) in the subacute phase of KD (Odds ratio 17.25, P =
      0.005). The findings in the present study indicate that an imbalance exists in
      the production between VEGF and ES in patients with KD while also suggesting that
      KD patients with a high VEGF/ES ratio have a significantly greater risk of CAL
      involvement.

PMID- 15730406
TI  - Male testosterone: what is normal?

PMID- 15730407
TI  - Vitamin D and the elderly.
AB  - This review summarizes current knowledge on vitamin D status in the elderly with
      special attention to definition and prevalence of vitamin D insufficiency and
      deficiency, relationships between vitamin D status and various diseases common in
      the elderly, and the effects of intervention with vitamin D or vitamin D and
      calcium. Individual vitamin D status is usually estimated by measuring plasma 25
      hydroxyvitamin D (25OHD) levels. However, reference values from normal
      populations are not applicable for the definition of vitamin D insufficiency or
      deficiency. Instead vitamin D insufficiency is defined as the lowest threshold
      value for plasma 25OHD (around 50 nmol/l) that prevents secondary
      hyperparathyroidism, increased bone turnover, bone mineral loss, or seasonal
      variations in plasma PTH. Vitamin D deficiency is defined as values below 25
      nmol/l. Using these definitions vitamin D deficiency is common among community
      dwelling elderly in the developed countries at higher latitudes and very common
      among institutionalized elderly, geriatric patients and patients with hip
      fractures. Vitamin D deficiency is an established risk factor for osteoporosis,
      falls and fractures. Clinical trials have demonstrated that 800 IU (20 microg)
      per day of vitamin D in combination with 1200 mg calcium effectively reduces the
      risk of falls and fractures in institutionalized patients. Furthermore, 400 IU
      (10 microg) per day in combination with 1000 mg calcium or 100 000 IU orally
      every fourth month without calcium reduces fracture risk in individuals over 65
      years of age living at home. Yearly injections of vitamin D seem to have no
      effect on fracture risk probably because of reduced bioavailability. Simulation
      studies suggest that fortification of food cannot provide sufficient vitamin D to
      the elderly without exceeding present conventional safety levels for children. A
      combination of fortification and individual supplementation is proposed. It is
      argued that all official programmes should be evaluated scientifically.
      Epidemiological studies suggest that vitamin D insufficiency is related to a
      number of other disorders frequently observed among the elderly, such as breast,
      prostate and colon cancers, type 2 diabetes, and cardiovascular disorders
      including hypertension. However, apart from hypertension, causality has not been
      established through randomized intervention studies. It seems that 800 IU (20
      microg) vitamin D per day in combination with calcium reduces systolic blood
      pressure in elderly women.

PMID- 15730409
TI  - Polycystic ovarian syndrome: marked differences between endocrinologists and
      gynaecologists in diagnosis and management.
AB  - BACKGROUND: Women with polycystic ovarian syndrome (PCOS) commonly consult
      endocrinologists or gynaecologists and it is not known whether these specialty
      groups differ in their approach to management. OBJECTIVE: To compare the
      investigation, diagnosis and treatment practices of endocrinologists and
      gynaecologists who treat PCOS. DESIGN AND SETTING: A mailed questionnaire
      containing a hypothetical patient's case history with varying presentations-
      oligomenorrhoea, hirsutism, infertility and obesity--was sent to Australian
      clinical endocrinologists and gynaecologists in teaching hospitals and private
      practice. RESULTS: Evaluable responses were obtained from 138 endocrinologists
      and 172 gynaecologists. The two specialty groups differed in their choice of
      essential diagnostic criteria and investigations. Endocrinologists regarded
      androgenization (81%) and menstrual irregularity (70%) as essential diagnostic
      criteria, whereas gynaecologists required polycystic ovaries (61%),
      androgenization (59%), menstrual irregularity (47%) and an elevated LH/FSH ratio
      (47%) (all P-values < 0.001). In investigation, gynaecologists were more likely
      to request ovarian ultrasound (91%vs. 44%, P < 0.001) and endocrinologists more
      likely to measure adrenal androgens (80%vs. 58%, P < 0.001) and lipids (67%vs.
      34%, P < 0.001). Gynaecologists were less likely to assess glucose homeostasis
      but more likely to use a glucose tolerance test to do so. Diet and exercise were
      chosen by most respondents as first-line treatment for all presentations.
      However, endocrinologists were more likely to use insulin sensitizers,
      particularly metformin, for these indications. In particular, for infertility,
      endocrinologists favoured metformin treatment whereas gynaecologists recommended
      clomiphene. CONCLUSIONS: There is a lack of consensus between endocrinologists
      and gynaecologists in the definition, diagnosis and treatment of PCOS. As a
      consequence, women may receive a different diagnosis or treatment depending on
      the type of specialist consulted.

PMID- 15730408
TI  - The value of an acute octreotide suppression test in predicting long-term
      responses to depot somatostatin analogues in patients with active acromegaly.
AB  - BACKGROUND: The long-acting depot somatostatin analogues [octreotide LAR (LAR)
      and lanreotide (LAN)] are among the most effective available medical therapies
      for acromegaly. However, published data on a biochemical test suitable for
      predicting the responsiveness to these depot agents are lacking. AIM: To
      investigate the value of an acute octreotide suppression test (OST) in predicting
      the responses to treatment with long-acting somatostatin analogues in patients
      with active acromegaly. PATIENTS AND METHODS: Thirty patients with active
      acromegaly [mean GH in GH day curve (GHDC) > 5 mU/l] were subjected to an OST
      [hourly GH measurements for 6 h following 100 microg subcutaneous (s.c.)
      octreotide]. Subsequently, 14 patients were treated with LAR, 10 with LAN and 6
      received both drugs at different times. The final response to treatment was
      evaluated when the subjects had achieved 'safe' GH levels (mean GH < 5 mU/l) or
      after receiving the maximal dose of each drug (maximum duration of treatment 6
      months). RESULTS: The nadir GH values during the OST were 2.6 +/- 2.5 mU/l (mean
      +/- SD, range 0.2-8.7) with a percentage fall of 84.8 +/- 15.7% (mean +/- SD,
      range 26-99%) from the baseline levels (26.2 +/- 31.5 mU/l, mean +/- SD). All the
      patients except one showed a decrease of greater than 50%. The mean time to
      achieve the nadir GH value was 3.8 +/- 1.6 h (mean +/- SD, range 1-6). The nadir
      GH levels showed a positive correlation with both pre-treatment (i.e. before
      commencing LAN or LAR) GH values during the GHDC (r = 0.63, P < 0.01) and IGF-I
      levels (r = 0.56, P < 0.05). The nadir GH values during the OST showed a positive
      correlation with the achieved mean GH levels in patients treated with LAR (r =
      0.66, P < 0.01) but not in the ones treated with LAN. The criterion of GH < 5.25
      mU/l during the OST had sensitivity 100%, specificity 80%, positive predictive
      value (PPV) 94% and negative predictive value (NPV) 100% in predicting
      achievement of 'safe' GH levels in patients treated with LAR. A less optimal
      prognostic profile was obtained for subjects treated with LAN with the criterion
      of GH < 6.05 mU/l during the OST providing sensitivity 92%, specificity 67%, PPV
      92% and NPV 67%. The above cut-off GH levels had a PPV of only 77% and 60% in
      predicting normalization of IGF-I on treatment with LAR or LAN, respectively.
      CONCLUSIONS: The OST is a reliable tool for the selection of patients with active
      acromegaly who will achieve 'safe' GH levels on therapy with LAR. Its prognostic
      profile is less optimal for patients treated with LAN. If GH values during the
      test fall < 5.25 mU/l (in case of LAR treatment) or < 6.05 mU/l (in case of LAN
      treatment), there is a 92-94% chance of subsequently achieving 'safe' GH levels
      after up to 6 months treatment with either of these agents.

PMID- 15730410
TI  - Comparison of the relationship of age and beta cell function in three ethnic
      groups.
AB  - DESIGN: Prevalence of type 2 diabetes and glucose intolerance increase with age.
      It has been demonstrated that beta cell function declines at about 1% per year in
      glucose tolerant Caucasians. However, this relationship is not known to exist in
      other ethnic groups. SUBJECTS AND MEASUREMENTS: We investigated the relationship
      of age to beta cell function (%B) and insulin sensitivity (%S), estimated by the
      homeostasis model assessment, in a nationally representative sample of healthy US
      adults who participated in a cross-sectional study, the third National Health and
      Nutrition Examination Survey. Only those subjects who had never been told to have
      diabetes by a physician, with HbA1C < 6% and fasting plasma glucose concentration
      < 5.56 mmol/l with proper fasting glucose and insulin concentration were included
      in this analysis (560 non-Hispanic whites, 231 non-Hispanic blacks and 298
      Hispanics). RESULTS: Age was positively correlated to HbA1C and fasting glucose
      concentration, but it was negatively correlated to %B in all three ethnic groups.
      In contrast, ageing had no influence on %S in all three ethnic groups. Pair-wise
      comparison showed age had a similar influence among three ethnic groups on
      fasting glucose concentration, HbA1C and %B, respectively. Multivariate analysis
      confirmed an independent influence of age on fasting glucose concentration, HbA1C
      and %B among three ethnic groups. CONCLUSIONS: We observed %B declines at about
      1% per year among all three ethnic groups. The age-related rising fasting plasma
      glucose concentration and HbA1C is most likely a consequence of age-related
      decline in beta cell function.

PMID- 15730411
TI  - Prospective screening for coeliac disease in patients with Graves'
      hyperthyroidism using anti-gliadin and tissue transglutaminase antibodies.
AB  - INTRODUCTION: Coeliac disease (CD) is associated with autoimmune thyroid disease
      (AITD) although its prevalence among those with Graves' hyperthyroidism in the UK
      is unknown. We determined the prevalence and evaluated the role of screening for
      CD prospectively in a consecutive cohort of patients with Graves' hyperthyroidism
      using IgA class antibodies to gliadin (AGA) and tissue transglutaminase (anti
      tTG). METHODS: All patients with Graves' hyperthyroidism attending the thyroid
      clinic over a 9-month period were offered screening for CD using AGA (normal < 3
      mg/l) and anti-tTG (normal < 15 micro/ml). Comparison was made with an age- and
      sex-matched healthy control group from the local population whose sera were
      tested for anti-tTG. In patients with borderline or raised anti-tTG (> 7
      micro/ml) endomysial antibody (EmA) was measured. Serum IgA was also measured to
      exclude IgA deficiency. Patients with raised AGA, raised or borderline anti-tTG,
      positive EmA, IgA deficiency or haematinic deficiencies were offered endoscopic
      duodenal biopsy. RESULTS: A total of 115 patients (97 female and 18 male) with
      Graves' hyperthyroidism were offered screening tests and 111 accepted. AGA was
      raised in 15 patients, anti-tTG was raised in two (both positive for EmA) and
      equivocal in six (one positive for EmA). IgA deficiency was present in three.
      Four patients were known to have haematinic deficiencies. Twenty-five patients
      were invited and 19 agreed to have endoscopic duodenal biopsy. Three new patients
      were found to have CD while two patients were already known to have CD, thus five
      of 111 patients with Graves' hyperthyroidism had CD. One of 115 healthy controls
      had a strong positive anti-tTG (> 200 micro/ml) and EmA indicating probable CD.
      CONCLUSIONS: Screening 111 consecutive patients with Graves' hyperthyroidism
      revealed AGA in 14%, anti-tTG in 2% and IgA deficiency in 3%. Two patients were
      known to have CD. Screening detected three new cases. The prevalence of CD in
      patients with Graves' hyperthyroidism was 4.5% as compared with 0.9% in matched
      healthy controls. Routine screening for CD should be considered.

PMID- 15730412
TI  - An update on the biochemical diagnosis of congenital ACTH insufficiency.
AB  - OBJECTIVE: Congenital ACTH insufficiency due to disorders of the hypothalamo
      pituitary axis is life threatening. However, the optimal method for establishing
      the diagnosis remains controversial. The standard Synacthen test (SST) is safe
      and easy to perform in infancy, but its performance has not been well evaluated
      in infants and children with ACTH insufficiency. DESIGN, PATIENTS AND
      MEASUREMENTS: We aimed to determine the value of the SST by comparing the 30-min
      SST cortisol concentration with physiological (spontaneous) cortisol secretion (2
      hourly measurements for 24 h) in 28 patients (13 male; age range 0-5.1 years)
      with one or a combination of optic nerve (25) midline forebrain (17) and other
      pituitary hormone (17) abnormalities. Spontaneous cortisol secretion (mean < 145
      nmol/l) was arbitrarily used as the 'gold-standard' in the diagnosis of ACTH
      insufficiency as it offered a reflection of endogenous cortisol mileu. A normal
      SST was defined as a 30-min serum cortisol > 540 nmol/l. RESULTS: The SST basal,
      30-min and 60-min serum cortisol concentrations were significantly (P < 0.001)
      lower in patients with ACTH insufficiency (mean spontaneous cortisol < 145
      nmol/l). 3/13 patients without and 12/15 patients with ACTH insufficiency failed
      the SST (specificity 76.9%; sensitivity 80%). Two out of three patients with ACTH
      insufficiency who passed the test were symptomatic with fatigue, poor growth and
      hypoglycaemia that resolved with hydrocortisone treatment. An 08:00 h serum
      cortisol cut-off of 175 nmol/l provided a sensitivity of 93.3% and a specificity
      of 92.3% as compared with spontaneous cortisol secretion. The 30-min increment
      and the 60-min SST cortisol concentrations although highly specific (100%) had
      reduced sensitivity (40% and 60%, respectively). CONCLUSIONS: A normal SST does
      not rule out ACTH insufficiency and measurement of physiological cortisol
      secretion may be required to confirm the diagnosis. A combination of 08:00 h
      serum cortisol > 175 nmol/l and a 30-min SST serum cortisol > 540 nmol/l to
      exclude ACTH insufficiency (sensitivity 69%, specificity 100%) would ensure that
      no child with ACTH insufficiency would be missed and hence would prevent serious
      consequences, although it may lead to over-diagnosis in some cases.

PMID- 15730413
TI  - Gender differences in growth hormone response to exercise before and after rhGH
      administration and the effect of rhGH on the hormone profile of fit normal
      adults.
AB  - OBJECTIVES: Exercise is a potent physiological stimulus of GH secretion. We
      hypothesized that exogenous recombinant human growth hormone (rhGH)
      administration through an increase in GH and IGF-I levels would blunt the GH
      response to exercise. The aim of the study was to examine and compare the impact
      of rhGH on the exercise-induced GH response in healthy normal men and women.
      DESIGN AND MEASUREMENTS: Sixty-nine subjects (36 men, 33 women) were randomized
      to receive low-dose rhGH (0.1 U/kg/day), high dose rhGH (0.2 U/kg/day), or
      placebo. Subjects were matched for age (24 +/- 3.1), and body mass index (BMI).
      rhGH was given as a single subcutaneous (s.c.) injection for the first 28 days.
      All subjects exercised to exhaustion (maximal oxygen consumption--VO2max) before
      rhGH treatment (Test 1), and on day 28 (Test 2). GH was measured before exercise
      (time 0), immediately after exercise (time 0') and at 15, 30, 60, 90 and 120 min
      postexercise. Baseline IGF-I levels were measured before exercise on days 0 and
      28. RESULTS: Baseline IGF-I levels showed no gender differences (42.3 women vs.
      38.8 nmol/l men) but basal GH values were higher in women (9.9 vs. 1.8 mU/l, P <
      0.001). The areas under the GH response curve, for Test 1 were similar in men and
      women. Peak GH values were higher in women than men (37.9 vs. 23.5 mU/l, but this
      did not quite reach statistical significance (P = 0.055). In men, administration
      of rhGH resulted in a significant increase in IGF-I levels over the basal state
      in both the LD and HD groups (P < 0.0001). In women, the increase in lGF-I levels
      reached significance only in the HD group (P < 0.0001). On day 28, GH secretion
      in response to exercise was calculated from the areas under the GH response curve
      correcting for an exogenous rhGH component (delta AUC). In men, the delta AUC,
      for Test 2 were similar in all three groups. In women, the delta AUC was higher
      in the placebo group, than in the HD group (P < 0.02). Free T4 levels decreased
      significantly in men, and free T3 increased in both men and women, in HD group
      after the rhGH administration. TSH levels were suppressed only in women. No
      changes in sex hormones were found in men or women in any of the treatment
      groups. Conclusions In terms of IGF-I, men are more responsive to rhGH treatment
      than women. In addition, as men, but not women, were able to overcome the
      negative feedback control of the elevated IGF-I levels, it seems that exercise
      may be a more robust stimulus to GH release in men compared to women.

PMID- 15730414
TI  - Determination of large bowel length and loop complexity in patients with
      acromegaly undergoing screening colonoscopy.
AB  - BACKGROUND: Patients with acromegaly are at moderately increased risk of
      developing colorectal cancer and may be considered for screening colonoscopy. In
      turn, large bowel dimensions may be increased in these patients, factors that
      predict for increased risk of serious complications such as perforation.
      OBJECTIVE: To evaluate this risk potential, we measured large bowel length and
      loop complexity using magnetic endoscopic imaging (MEI). DESIGN: Case-control
      study in 25 unselected patients with acromegaly (mean age 56 years) vs. 41
      nonacromegalic controls (mean age 60 years) undergoing screening colonoscopy.
      MEASUREMENTS: MEI parameters were determined and age- and sex-adjusted mean
      differences calculated. The dependency of total large bowel length on various
      demographic and disease-related factors (e.g. GH exposure, IGF-I and IGFBP-3
      concentrations) was assessed using regression techniques. RESULTS: Total large
      bowel length was increased by 20%[95% confidence interval (CI) 9-31%] in patients
      with acromegaly compared with controls (unadjusted and adjusted; P-values <
      0.001). Acromegaly was also associated with increased time taken to reach the
      caecum (P = 0.01) and increased pelvic loop complexities (5/25 vs. 1/41, Fisher's
      exact test: P = 0.03). Total large bowel length was predicted by age at
      colonoscopy (P = 0.003) and patient height (P = 0.03), but not by surrogate
      biochemical markers of disease activity. CONCLUSIONS: Acromegaly is associated
      with increased large bowel length and loop complexity making colonoscopy
      technically challenging, and theoretically increasing the risk of serious
      complications. Patients need to be counselled accordingly, and appropriate
      resources with experienced staff allocated.

PMID- 15730415
TI  - Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20
      years' retrospective study.
AB  - OBJECTIVE: To investigate the risk of hypothyroidism after radioiodine (131I)
      treatment for hyperfunctioning thyroid nodules. DESIGN: Retrospective analysis of
      patients treated with 131I for hyperfunctioning thyroid nodules and followed up
      for a maximum of 20 years. PATIENTS: A total of 346 patients treated with 131I in
      the years 1975-95, for a single hyperfunctioning nodule. MEASUREMENTS:
      Hypothyroidism was defined as TSH levels > 3.7 mU/l. Kaplan-Meier survival
      analysis was used to analyse permanence of euthyroidism after 131I. A stepwise
      Cox proportional hazard model was used to identify factors influencing the
      progression to hypothyroidism. RESULTS: The cumulative incidence of
      hypothyroidism was 7.6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20
      years. Age (P < 0.01), 24-th 131I uptake (P < 0.05) and previous treatment with
      methimazole (MMI, P < 0.1) were associated with a faster progression towards
      hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and
      degree of extranodular thyroid parenchymal suppression had no influence. In
      hyperthyroid patients with partial parenchymal suppression, however, previous MMI
      treatment was the most important prognostic factor (P < 0.01). CONCLUSIONS: After
      20 years of follow-up, 60% of patients treated with 131I for a single
      hyperfunctioning nodule are hypothyroid. Factors increasing the risk of
      hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of
      this last factor, however, depends on the degree of suppression of the
      extranodular thyroid parenchyma at the scan.

PMID- 15730416
TI  - Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1.
AB  - OBJECTIVE: To identify MEN1 gene mutations and characterize clinical
      manifestations in Chinese kindred with multiple endocrine neoplasia type 1 (MEN1)
      in Taiwan. PATIENTS AND METHODS: Eight unrelated subjects (one male and seven
      females, age range 26-70 years) with clinical manifestations of MEN1 were
      analysed. In addition, 45 relatives that included 10 affected (three males and
      seven females, age range 32-53 years) and 35 unaffected (17 males and 18 females,
      age range 15-80 years) subjects were evaluated. Genomic DNA extraction,
      polymerase chain reaction (PCR) and DNA sequence analysis were performed
      according to standard procedures. RESULTS: We identified heterozygous MEN1 gene
      mutations in all eight probands and 10 affected subjects as well as in 13
      clinically asymptomatic relatives. Novel mutations included a missense mutation
      in a heterozygous mutation in exon 9 (GAC --> CAC) resulting in a substitution of
      aspartic acid by histidine at codon 418 (family 1); a nonsense mutation at codon
      556 of exon 10 (GAG --> TAG) resulting in a stop codon and termination (family
      2); a missense mutation in exon 2 (GGG --> GAG) causing the substitution of
      glycine by glutamic acid at codon 110 (family 3); and a deletion/insertion
      mutation in nucleotide 1200 of exon 8 resulting in frameshift and early
      termination (family 4). Affected subjects in families 5-7 shared the same C
      insertion at nucleotide 1650 of exon 10, similar to that previously described as
      a hotspot for mutation, and proband 8 had a previously described mutation in
      intron 4 of the MEN1 gene (IVS4-9 G --> A). We also found that 18 (58%) of our 31
      MEN1 mutant carriers had clinical symptoms, whereas four (13%) had biochemical
      abnormalities without clinical symptoms, and nine (29%) were unaffected both
      clinically and biochemically. CONCLUSIONS: We have identified four novel
      mutations in the MEN1 gene in patients with MEN1 in Taiwan.

PMID- 15730417
TI  - Normal opioid tone and hypothalamic-pituitary-adrenal axis function in chronic
      fatigue syndrome despite marked functional impairment.
AB  - OBJECTIVE: To determine whether the functional impairment seen in chronic fatigue
      syndrome (CFS) is associated with reduced levels of central opioids and/or
      deficiency of the hypothalamic-pituitary-adrenal (HPA) axis. DESIGN: Single
      blinded case-control study measuring functional and psychological status, basal
      hormonal parameters and ACTH/cortisol response to naloxone and ovine
      corticotrophin-releasing hormone (oCRH) vs. placebo in people with CFS and
      healthy controls. PATIENTS: Twelve people with CFS and 11 age-matched controls.
      MEASUREMENTS: Hormonal parameters: basal levels of 09:00 h plasma cortisol,
      dehydroepiandrosterone sulfate (DHEAS) and IGF-1. 24-h urinary free cortisol.
      Plasma ACTH and cortisol response to naloxone 125 microg/kg, oCRH 1 microg/kg and
      placebo (normal saline). Psychological parameters: SF-36, Hamilton Depression
      Score, Hospital Anxiety and Depression Scale and Fatigue Scale. RESULTS: There
      were highly significant differences between the CFS subjects and the controls
      with respect to the measures of fatigue and physical functioning. However, there
      were no differences in basal levels of 09:00 h cortisol (367 +/- 37 vs. 331 +/-
      39 nmol/l, P = 0.51), DHEAS (4.2 +/- 0.6 vs. 4.0 +/- 0.5 micromol/l, P = 0.81),
      24-h urinary free cortisol (182 +/- 27 vs. 178 +/- 21 nmol/24 h, P = 0.91) or IGF
      1 (145 +/- 19 vs. 130 +/- 11 microg/l, P = 0.52) between the CFS group and
      controls, respectively. There was also no difference between the groups with
      respect to the ACTH and cortisol response to either oCRH or naloxone.
      CONCLUSIONS: Our data do not support an aetiological role for deficiency in
      central opioids or the HPA axis in the symptoms of CFS.

PMID- 15730418
TI  - The changes in circulating osteoprotegerin after hormone therapy in
      postmenopausal women and their relationship with oestrogen responsiveness on
      bone.
AB  - OBJECTIVE: Oestrogen replacement reduces the increased rate of bone remodelling
      after the menopause. Osteoprotegerin (OPG) is a negative regulator of osteoclast
      mediated bone resorption. In vitro studies have shown that oestrogen stimulates
      OPG production. However, the role of OPG in physiological bone remodelling and
      its regulation by oestrogen in vivo remain controversial. In this study, we
      analysed the association between changes in serum OPG levels and bone turnover
      status before and after hormone therapy (HT) in healthy postmenopausal women.
      PATIENTS AND MEASUREMENTS: Ninety-nine healthy postmenopausal women of Korean
      ethnicity, aged 42-64 years (52.3 +/- 4.9 years, mean +/- SD) were enrolled in
      our study. Serum OPG levels were assessed by a highly sensitive sandwich-type
      enzyme immunoassay. Serum concentrations of osteocalcin (OC) and carboxyterminal
      telopeptides (CTx) were determined by electrochemiluminescence immunoassays. Bone
      mineral density (BMD) at the lumbar spine and femoral neck was measured by dual
      energy X-ray absorptiometry (DEXA). RESULTS: Baseline levels of OPG correlated
      neither a the bone formation marker, serum OC, nor with a bone resorption marker,
      serum CTx. No significant association of baseline OPG was found with baseline BMD
      measured at the lumbar spine and femoral neck. Serum OPG levels measured after 3
      months and 1 year of HT decreased significantly compared to baseline (P < 0.001
      in both). The changes in circulating OPG at 3 months of HT correlated with the
      changes in both serum OC (r = 0.226, P = 0.029) and serum CTx (r = 0.214, P =
      0.038) at 3 months after HT. However, there was no significant association
      between the changes in circulating OPG after 3 months of HT and BMD values of the
      lumbar spine or femoral neck after 1 year of HT. CONCLUSIONS: Our results suggest
      that baseline OPG levels do not reflect bone turnover status and that serial
      measurements of serum OPG after HT are not a useful predictor of the long-term
      effects of oestrogen on bone density. The decrease in serum concentrations of OPG
      after HT may occur to compensate for the action of oestrogen in suppressing bone
      resorption.

PMID- 15730419
TI  - Beta-cell dysfunction and low insulin clearance in insulin-resistant human
      immunodeficiency virus (HIV)-infected patients with lipodystrophy.
AB  - OBJECTIVE: To obtain a better understanding of the physiological aspects of
      glucose homeostasis in human immunodeficiency virus (HIV)-infected patients with
      lipodystrophy, we evaluated separately beta-cell function and insulin sensitivity
      after an oral glucose load. DESIGN: Beta-cell function was investigated during an
      oral glucose tolerance test (OGTT) (75 g, 180 min) in 16 lipodystrophic HIV
      infected patients and in 15 age- and weight-matched nonlipodystrophic HIV
      infected patients. All participants were sedentary Caucasian males, who were on
      highly active antiretroviral therapy with no history of diabetes mellitus or
      impaired glucose tolerance. Prehepatic insulin secretion rates were estimated by
      deconvolution of C-peptide concentrations. A composite measure of insulin
      sensitivity was derived from the OGTT. RESULTS: Beta-cell secretory capacity
      (i.e. the rate of change in insulin secretion per unit change in glucose
      concentration) was similar in lipodystrophic and nonlipodystrophic patients (6.2
      +/- 1.0 mU kg(-1) min(-1) mg(-1) dl vs. 5.4 +/- 0.4, P > 0.4), but insulin
      sensitivity was reduced by 61% in lipodystrophic patients (P < 0.004). The
      disposition index (insulin capacity multiplied with insulin sensitivity) and
      insulin clearance rate were reduced in lipodystrophic patients (-55%, P < 0.003
      and -31%, P < 0.004). Insulin clearance rate correlated strongly with insulin
      sensitivity (r = 0.82, P < 0.001). More lipodystrophic than nonlipodystrophic
      patients exhibited impaired glucose tolerance and diabetes mellitus (63%vs. 20%,
      P < 0.05). CONCLUSIONS: Our data support the concept that impaired glucose
      tolerance in lipodystrophic HIV-infected patients relates to a failure of the
      beta-cells to fully compensate for decrements in insulin sensitivity despite
      simultaneous reduction in insulin clearance.

PMID- 15730420
TI  - No association of the codon 55 methionine to valine polymorphism in the SUMO4
      gene with Graves' disease.
AB  - OBJECTIVE: A functional polymorphism at codon 55 of the small ubiquitin-like
      modifier-4 (SUMO4) gene (methionine to valine; M55V) has recently been associated
      with type 1 diabetes mellitus (T1D). We aimed to establish whether this locus
      also contributes towards the genetic susceptibility to Graves' disease (GD) and
      autoimmune Addison's disease. DESIGN: A case-control analysis was performed using
      genomic DNA samples from 595 unrelated white GD subjects, 104 white autoimmune
      Addison's disease subjects and 467 healthy white control subjects. The SUMO4 M55V
      single nucleotide polymorphism (SNP) was genotyped using polymerase chain
      reaction (PCR) amplification followed by digestion with the restriction enzyme
      MseI. RESULTS: There was no association of the SUMO4 M55V alleles with either GD,
      thyroid-associated orbitopathy or autoimmune Addison's disease when compared to
      controls; P = 0.28, 0.46 and 0.91, respectively, by chi2 testing. CONCLUSION: We
      cannot confirm a generalized role for SUMO4 in autoimmune endocrinopathy. The
      SUMO4 codon 55 methionine to valine polymorphism may be exclusively associated
      with susceptibility to T1D, or the effect of the locus in GD and Addison's
      disease may be much less than that found in T1D patients.

PMID- 15730421
TI  - Neonatal leptin levels are strongly associated with female gender, birth length,
      IGF-I levels and formula feeding.
AB  - OBJECTIVE: To investigate predictors of circulating leptin in healthy full-term
      newborns and to explore the relationship with anthropometric variables, serum
      levels of adiponectin and the major components of the IGF system at birth. To
      explore whether leptin levels are regulated by breastfeeding vs. formula feeding.
      DESIGN: Observational cross-sectional study. PATIENTS: Three hundred and nineteen
      healthy full-term newborns delivered during 1999 in Athens, Greece. MEASUREMENTS:
      Anthropometric measurements, formula feeding information and blood samples were
      obtained. Leptin and adiponectin determinations were performed using a
      radioimmunoassay (RIA). RESULTS: Multivariate regression analyses showed that
      leptin levels were positively associated with female gender, newborn length,
      ponderal index and IGF-I levels, but not with adiponectin levels. Newborns who
      were fed exclusively with milk formulas had more than twice the leptin levels of
      those who were exclusively breastfed. CONCLUSIONS: Leptin levels are positively
      related to female gender and anthropometric characteristics of neonates but,
      contrary to studies in adults, are not correlated with adiponectin levels. We
      also found evidence that formula feeding imparts a considerable increase in
      leptin levels in newborns.

PMID- 15730422
TI  - Growth hormone deficiency and coeliac disease: an unusual association?
AB  - OBJECTIVE: To assess the occurrence of growth hormone deficiency (GHD) in
      patients with coeliac disease (CD). STUDY DESIGN: A total of 1066 children
      diagnosed elsewhere with short stature were referred to our centre for second
      line evaluation in a 6-year period. All patients were screened for CD by
      antiendomysial antibodies (EMA) and those with positive sera underwent intestinal
      biopsy. RESULTS: Among the 1066 short children, 210 (19.7%) had GHD and 12
      (1.12%; chronological age from 3.6 to 12.3 years, bone age from 1.5 to 10.5
      years, SDS height from -3.05 to -0.48), having positive EMA, showed
      histologically confirmed CD. Nine of these latter 12 CD children had a beneficial
      effect on growth rate after the first year of gluten-free diet, while the
      remaining three showed no catch-up growth. A careful endocrinological
      investigation in these three CD boys showed an isolated GHD in two cases and a
      multiple GHD in one case. The congenital origin of GHD is supported by the
      congenital abnormalities documented by magnetic resonance imaging. GH therapy
      associated with gluten-free diet led to an increased growth rate. CONCLUSION: GH
      secretion should be evaluated in coeliac patients showing no catch-up growth
      after a period on a gluten-free diet in spite of reversion to seronegativity for
      EMA. In the case of GHD and CD, replacement GH therapy should be started during a
      gluten-free diet.

PMID- 15730423
TI  - Neck recurrence from thyroid carcinoma: serum thyroglobulin and high-dose total
      body scan are not reliable criteria for cure after radioiodine treatment.
AB  - BACKGROUND: Local and regional recurrences occur in up to 20% of patients with
      papillary and follicular thyroid carcinoma. Diagnostic work-up and treatment
      modalities are still controversial, because nodal control is difficult to
      ascertain. We assessed the value of serum thyroglobulin (Tg) determination and of
      high-dose 131I total body scan (TBS) for ascertaining the absence of disease in
      patients who had already been treated with radioiodine and who subsequently
      underwent surgery. METHODS: Between 1990 and 2000, 105 patients who had been
      treated with radioiodine for lymph node recurrence with initial 131I uptake were
      included in a standardized protocol performed after withdrawal of thyroid hormone
      treatment: on day 1, serum Tg determination and administration of 3.7 GBq 131I;
      on day 4, 131I TBS; on day 5, surgery; on day 8, 131I TBS. RESULTS: In 25
      patients the serum Tg obtained following thyroid hormone withdrawal was
      undetectable: for these patients, the 131I TBS showed uptake foci in 21 and
      pathology disclosed neoplastic foci in 19. In 32 patients the serum Tg ranged
      from 1 to 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 26 and
      pathology disclosed neoplastic foci in 28. In 48 patients the serum Tg level was
      above 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 38 and
      pathology disclosed neoplastic foci in 46. Thus, no uptake was found
      preoperatively in 20 patients, among whom pathology disclosed lymph node
      metastases in 16. However, both tests were negative in only two of the 93
      patients in whom pathology disclosed neoplastic foci. CONCLUSION: Serum Tg levels
      and 131I TBS cannot be considered as reliable indicators for the absence of
      disease in patients already treated with 131I. However, when both tests are
      negative, the risk of persistent disease is minimal.

PMID- 15730424
TI  - The relative importance of genetic and environmental factors in the aetiology of
      thyroid nodularity: a study of healthy Danish twins.
AB  - BACKGROUND: A large proportion of healthy, euthyroid, nongoitrous individuals
      have thyroid nodules. The aetiology of these ultrasonographically detected
      morphological abnormalities is largely unknown. Factors such as age, gender,
      iodine intake, smoking and parity are associated with nodularity of the thyroid.
      Whether there is a genetic susceptibility is unclear. AIM: To gain insight into
      the aetiology of thyroid nodularity by investigating a large cohort of healthy
      euthyroid monozygotic and dizygotic twins. DESIGN: A cross-sectional twin study.
      PARTICIPANTS: A representative sample of self-reported healthy twin pairs was
      identified through the Danish Twin Registry. A total of 520 individuals divided
      into 104 monozygotic (MZ), 107 dizygotic same sex (DZ) and 49 opposite sex (OS)
      twin pairs were investigated. MEASUREMENTS: Probandwise concordance and
      tetrachoric correlations. Quantitative genetic modelling was used to elucidate
      the relative importance of genetic and environmental effects for the variation in
      the liability of nodularity. RESULTS: A higher concordance rate for thyroid
      nodularity was found in MZ twins [0.57 (95% CI 0.36-0.76)] than in DZ twins [0.36
      (95% CI 0.17-0.56, P = 0.074)]. The same was true for tetrachoric correlations:
      0.67 (95% CI 0.34-0.87) in MZ twins and 0.17 (CI - 0.28-0.56, P = 0.053) in DZ
      twins. The difference, although not significant, was more pronounced for multiple
      nodules than for solitary nodules. Controlling for covariates (age, gender and
      smoking habits), it was calculated that genetic factors accounted for 67% (95% CI
      35-87%) and environmental factors for 33% (95% CI 13-65%) of the individual
      differences in the liability to thyroid nodularity. CONCLUSIONS: This study
      suggests that genetic factors are of aetiological importance for thyroid
      nodularity in clinically healthy and euthyroid individuals, and indicates a
      difference in the aetiology of solitary and multiple thyroid nodules.

PMID- 15730426
TI  - A channel in a transporter.
AB  - 1. Glutamate transporters (or excitatory amino acid transporters (EAAT)) are
      responsible for removing synaptically released glutamate from the extracellular
      space. The failure of EAAT to carry out this role will lead to excessive
      stimulation of glutamatergic receptors, causing excitotoxicity and cell death. 2.
      Glutamate is cotransported into the cell with three Na+ and one H+, followed by
      the counter-transport of one K+. In addition, glutamate and Na+ binding activates
      an uncoupled chloride conductance. Thus, glutamate transporters can function as
      both a transporter and an ion channel. At present, there is no clear
      understanding of the structural basis for the dual functions of glutamate
      transporters and, in the present review, we shall discuss some recent studies
      that have started to address this question. 3. It is possible to modulate one
      function of glutamate transporters without affecting the other, which suggests
      that the two functions have separate molecular determinants, and a number of
      models have been suggested to account for the dual functions of the EAAT that
      predict both single and dual pores for transporter function. 4. It appears that
      the two functions of glutamate transporters arise from separate transmembrane
      domains. The C-terminal region of the transporters forms the glutamate
      translocation domain, whereas the second transmembrane domain in the N-terminal
      half of the protein plays a crucial role in chloride channel function. Although
      the two functions arise from separate molecular determinants, the two functional
      domains are likely to be in close proximity. The significance of these
      observations will be discussed in terms of likely functional models for the
      transport and channel processes.

PMID- 15730427
TI  - Neurotoxic effects of venoms from seven species of Australasian black snakes
      (Pseudechis): efficacy of black and tiger snake antivenoms.
AB  - 1. Pseudechis species (black snakes) are among the most widespread venomous
      snakes in Australia. Despite this, very little is known about the potency of
      their venoms or the efficacy of the antivenoms used to treat systemic
      envenomation by these snakes. The present study investigated the in vitro
      neurotoxicity of venoms from seven Australasian Pseudechis species and determined
      the efficacy of black and tiger snake antivenoms against this activity. 2. All
      venoms (10 microg/mL) significantly inhibited indirect twitches of the chick
      biventer cervicis nerve-muscle preparation and responses to exogenous
      acetylcholine (ACh; 1 mmol/L), but not to KCl (40 mmol/L), indicating activity at
      post-synaptic nicotinic receptors on the skeletal muscle. 3. Prior administration
      of either black or tiger snake antivenom (5 U/mL) prevented the inhibitory
      effects of all Pseudechis venoms. 4. Black snake antivenom (5 U/mL) added at t90
      (i.e. the time-point at which the original twitch height was reduced by 90%)
      significantly reversed the effects of P. butleri (28+/-5%), P. guttatus (25+/-8%)
      and P. porphyriacus (28+/-10%) venoms. Tiger snake antivenom (5 U/mL) added at
      the t90 time-point significantly reversed the neurotoxic effects of P. guttatus
      (51+/-4%), P. papuanus (47+/-5%) and P. porphyriacus (20+/-7%) venoms. 5. We
      show, for the first time, the presence of neurotoxins in the venom of these
      related snake species and that this activity is differentially affected by either
      black snake or tiger snake antivenoms.

PMID- 15730428
TI  - Pharmacokinetics of high doses of cyanocobalamin administered by intravenous
      injection for 26 weeks in rats.
AB  - 1. High doses of vitamin B12 (cyanocobalamin) may be therapeutically effective to
      treat neurological alterations secondary to a wide range of disease states. The
      aim of the present study was to evaluate the effect of dose and repeated
      administration on the pharmacokinetics of cyanocobalamin in rats. 2. Forty-eight
      rats were randomly assigned to receive 1, 5, 25 or 100 mg/kg cyanocobalamin for
      182 days (26 weeks). Cyanocobalamin plasma levels were quantified by HPLC on days
      1, 85 and 182 of treatment and were analysed by means of non-compartment
      pharmacokinetic (PK) analysis. In addition, population PK analysis was used to
      fit cyanocobalamin plasma concentrations to time by means of a two-compartment
      model for intravascular administration. 3. The half-life of cyanocobalamin ranged
      from approximately 20 to 50 min, clearance ranged from 4.5 to 9 mL/min and the
      volume of distribution at steady state ranged from 140 to 470 mL. A statistically
      significant negative relationship existed between the dose of cyanocobalamin and
      the normalized area under the plasma concentration-time curve (AUC). This non
      linearity was not exhibited in population PK analysis. No evidence of toxicity
      was observed. 4. At very high and prolonged doses (up to 100 mg/kg for 26 weeks),
      intravascular administration of cyanocobalamin in rats follows a two-compartment
      kinetic model and cyanocobalamin undergoes extensive extravascular distribution.
      The negative relationship between dose and normalized AUC is compatible with
      possible saturation of tubular reabsorption, thus increasing renal clearance at
      higher doses.

PMID- 15730429
TI  - Hypotensive and lipid regulatory actions of 4-hydroxyderricin, a chalcone from
      Angelica keiskei, in stroke-prone spontaneously hypertensive rats.
AB  - 1. Previously, we found that Angelica keiskei extract (ethyl acetate extract from
      the yellow liquid of stems) elevated serum high-density lipoprotein (HDL) levels
      and reduced liver triglyceride content in stroke-prone spontaneously hypertensive
      rats (SHRSP). To identify the active substance in A. keiskei extract, we examined
      the effect of 4-hydroxyderricin, a characteristic chalcone isolated from the
      yellow liquid of stems, on blood pressure and lipid metabolism in SHRSP. 2. Six
      week-old male SHRSP were fed diets containing 0.07% 4-hydroxyderricin for 7 weeks
      with free access to the diet and water. Elevation of systolic blood pressure was
      significantly suppressed after 7 weeks treatment. Serum very low-density
      lipoprotein (VLDL) levels were significantly reduced, without any effect on HDL
      levels, and were associated with a significant decrease in the serum
      concentration of free fatty acids. 3. In the liver, significant decreases in
      relative liver weight and triglyceride content were found after treatment with 4
      hydroxyderricin for 7 weeks. 4. An investigation of hepatic mRNA expression of
      proteins involved in lipid metabolism indicated that a significant decrease in
      microsomal triglyceride transferprotein may be responsible for the decrease in
      serum VLDL levels and that significant decreases in adipocyte determination and
      differentiation factor 1 and fatty acid synthase may be responsible for the
      decrease in hepatic triglyceride content. 5. In conclusion, dietary 4
      hydroxyderricin produces suppression of the elevation of systolic blood pressure,
      reduction of serum VLDL levels and a decrease in hepatic triglyceride content in
      SHRSP.

PMID- 15730430
TI  - Effects of post-treatment with low-dose propofol on inflammatory responses to
      lipopolysaccharide-induced shock in conscious rats.
AB  - 1. In the present study, we used a low dose of propofol (5 mg/kg per h) to
      investigate its effects on the pro-inflammatory cytokines (tumour necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta and IL-10) and changes in nitric oxide (NO)
      following lipopolysaccharide (LPS) for a period of 12 h in conscious rats. 2.
      Experiments were designed to induce endotoxin shock by intravenous injection of
      Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Arterial pressure (AP)
      and heart rate (HR) were monitored continuously for 12 h after LPS
      administration. Tumour necrosis factor-alpha, IL-1beta, IL-10 and plasma
      nitrates/nitrites were determined before and 0.5, 1, 3, 6, 9 and 12 h after LPS
      administration. A low dose of intravenous propofol (5 mg/kg per h) was
      administered to investigate the effects on cytokine responses and changes in NO
      in endotoxin shock. 3. Lipopolysaccharide significantly increased TNF-alpha, IL
      1beta, IL-10, nitrites/nitrates and HR, whereas mean AP was decreased. Post
      treatment with propofol suppressed the release of TNF-alpha, IL-1beta, IL-10 and
      NO production after endotoxin shock. 4. Lipopolysaccharide also caused a decrease
      in the white blood cell count and haematocrit. 5. Post-treatment with propofol
      slightly, but not significantly, affected the LPS-induced systemic hypotension,
      tachycardia, leukocytopenia and anaemia. 6. These findings suggest that low-dose
      propofol may be beneficial to the inflammatory change in sepsis.

PMID- 15730431
TI  - Anterior hypothalamic beta-adrenoceptors in chronic aortic-coarctated
      hypertensive rats: an interaction with central angiotensin II receptors.
AB  - 1. The aim of the present study was to investigate the activity of anterior
      hypothalamic beta-adrenoceptors and angiotensin (Ang) II receptors on blood
      pressure in normotensive rats and aortic-coarctated (ACo) animals at a chronic
      stage of hypertension. A possible interaction between beta-adrenoceptors and
      AngII pressor activity was also investigated. 2. Injection of isoproterenol (0.1
      10 nmol) in the anterior hypothalamic area induced a dose-dependent decrease in
      mean arterial pressure (MAP) in sham-operated (SO), but not in ACo, animals.
      Isoproterenol (1 nmol) reduced blood pressure in SO rats (DeltaMAP -10.1+/-1.4
      mmHg; n=10) but not in ACo animals (DeltaMAP -0.9+/-1.6 mmHg; n=10; P<0.05 vs SO
      rats). Whereas previous administration of atenolol (40 nmol) enhanced the
      cardiovascular effect of isoproterenol (1 nmol) in ACo rats but not in SO
      animals, propranolol (40 nmol) prevented the hypotensive action of isoproterenol
      in both experimental groups. Intrahypothalamic administration of clenbuterol
      decreased MAP in a dose-dependent manner; however, the depressor response to
      clenbuterol (10 nmol) was greater in ACo rats than in SO rats (DeltaMAP -26.8+/
      3.2 vs -14.4+/-2.4 mmHg, respectively; n=5 for both; P<0.05). When AngII (50 ng)
      was injected into the anterior hypothalamic area, a greater pressor response was
      observed in ACo rats than in SO rats (DeltaMAP 19.6+/-1.1 vs 11.3+/-0.6 mmHg,
      respectively; n=5 for both; P<0.05). Atenolol (40 nmol) pretreatment partially
      and significantly prevented the pressor response to AngII in ACo rats, but not in
      SO rats. 3. In conclusion, these results provide pharmacological evidence for the
      existence of a beta1-adrenoceptor-mediated pressor mechanism in the anterior
      hypothalamic area of ACo rats that is absent in SO rats. The enhanced depressor
      beta2-adrenoceptor activity observed in chronic ACo rats could be a compensatory
      adjustment to pressor beta1-adrenoceptor activity. Conversely, pressor
      overactivity of AngII was observed in the anterior hypothalamic area of ACo rats
      at a chronic hypertensive stage; this enhancement could be explained, at least in
      part, by the pressor beta1-adrenoceptor activity.

PMID- 15730432
TI  - Gender differences in blood pressure and heart rate in spontaneously hypertensive
      and Wistar-Kyoto rats.
AB  - 1. In general, premenopausal women are known to have lower blood pressure than
      men and animal models have shown a similar sexual dimorphism. However, many
      studies in animals have been performed using anaesthetized or restrained models.
      Current experiments were conducted to investigate the relationships among resting
      heart rate, blood pressure and gender in conscious, unrestrained normotensive
      Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2.
      Biotelemetry transmitters were implanted in 6-month-old animals. Values for heart
      rate, diastolic blood pressure, systolic blood pressure and pulse pressure were
      recorded continuously at 10 min intervals after all animals recovered completely
      from surgery. 3. Normal circadian rhythms in heart rate were found in all rats,
      with no significant differences among the four groups; the circadian variation in
      blood pressure was evident in all groups, although much smaller. Heart rate was
      found to be higher in WKY female rats than in the other three groups. Male WKY
      rats, male SHR and female SHR had similar heart rates. Male SHR had significantly
      higher systolic and diastolic blood pressures than female SHR. Male and female
      WKY rats had similar diastolic blood pressure, but males had slightly higher
      systolic pressure than females. No significant difference in pulse pressure was
      found in WKY male and female rats. Male SHR showed significantly higher pulse
      pressure than female SHR at most times during the day. 4. In conclusion, these
      results indicate that hypertension is exacerbated in male SHR compared with
      females under conscious resting conditions and demonstrate that the higher heart
      rate observed in WKY female rats is not present in the SHR model.

PMID- 15730433
TI  - Possible anti-atherogenic effect of kolaviron (a Garcinia kola seed extract) in
      hypercholesterolaemic rats.
AB  - 1. The hypolipidaemic effect of kolaviron, a mixture of Garcinia biflavonoid 1
      (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of
      various ailments in southern Nigeria, was investigated in rats. The ability of
      Questran (Bristol-Myers Squibb, Hounslow, UK), a hypolipidaemic therapeutic drug,
      to attenuate hypercholesterolaemia in rats was also examined. 2. In order to
      assess the hypolipidaemic effect of this extract in experimental animals,
      thiobarbituric acid-reactive substances (TBARS), cholesterol, phospholipid, low
      density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and
      triglyceride levels were determined in the plasma and liver. 3. Cholesterol
      administered orally to rats at a dose of 30 mg/0.3 mL five times a week for 8
      consecutive weeks resulted in a significant increase (P<0.001) in the relative
      weight of the heart of hypercholesterolaemic animals compared with control.
      However, cotreatment with kolaviron and Questran ameliorated the cholesterol
      induced enlargement of the heart. Kolaviron (100 and 200 mg/kg) elicited 88.5 and
      87.4% reductions, respectively, in plasma cholesterol levels of pretreated
      animals compared with the cholesterol-fed group. In addition, kolaviron produced
      a significant decrease (P<0.05) in post-mitochondrial fraction (PMF) cholesterol
      levels in treated animals compared with untreated hypercholesterolaemic animals.
      Similarly, Questran significantly decreased (P<0.05) the cholesterol-induced
      increase in plasma cholesterol levels compared with untreated
      hypercholesterolaemic animals. In addition, (100 and 200 mg/kg) significantly
      (P<0.05) decreased plasma LDL-C levels by over 70% in treated animals compared
      with untreated hypercholesterolaemic animals. Similarly, kolaviron significantly
      decreased (P<0.05) PMF LDL-C levels by over 60% in treated animals compared with
      untreated hypercholesterolaemic animals. 4. The significantly (P<0.05) higher
      values of plasma and PMF triglycerides obtained in cholesterol-fed animals
      compared with control animals were unaltered following cotreatment with kolaviron
      and Questran. In the present study, there was a significant decrease (P<0.05) in
      plasma formation of malondialdehyde in kolaviron- and Questran-treated animals
      compared with untreated hypercholesterolaemic animals. 5. The results of the
      present study demonstrate that kolaviron exerts a hypocholesterolaemic effect and
      reduces the relative weight of the heart in cholesterol-fed animals. This
      reduction and the favourable lipid profile indicate a possible anti-atherogenic
      property of the extract.

PMID- 15730434
TI  - Caffeine-herbal ephedra combination increases resting energy expenditure, heart
      rate and blood pressure.
AB  - 1. The purpose of the present study was to determine whether the consumption of
      an acute dose of caffeine and Ma Huang increases resting energy expenditure
      (REE), heart rate (HR) and blood pressure (BP) over a 3 h period. 2. A
      randomized, double-blind cross-over study was performed evaluating the acute
      effects of caffeine (150 mg)/herbal ephedra (Ma Huang; 20 mg ephedra alkaloids)
      versus a placebo. A total of eight healthy subjects (four males and four females)
      with a mean (+/-SD) age of 23.4+/-0.8 years (mean ages for males and females:
      25.3+/-0.7 and 22.0+/-0.7 years, respectively) and 22.5+/-3.1% body fat (15.7+/
      1.2 and 27.6+/-3.5% body fat for males and females, respectively) were recruited
      to the study. Participants were moderate caffeine users (approximately 150-300
      mg/day). 3. Subjects reported to the laboratory following a 12 h fast and 48 h of
      a caffeine-free diet. Resting energy expenditure was measured prior to
      supplementation and for 15 min every 30 min for 3 h following supplementation.
      Heart rate and BP were obtained every 15 min. Blood samples were obtained every
      30 min following the measurement of REE and analysed for caffeine, ephedrine,
      free fatty acids and glucose. 4. By 3 h, HR was 22.7+/-5.5% higher (P<0.05) than
      baseline for the caffeine/ephedra trial compared with 8.9+/-2.2% higher for the
      placebo group. At 3 h, systolic BP was 9.1+/-2.2% higher (P<0.05) than baseline
      for the caffeine/ephedra trial compared with only 1.9+/-2.9% different from
      baseline for the placebo trial. There was no effect of the caffeine/ephedra
      combination on diastolic BP. Resting energy expenditure during the last 30 min
      was 4.5+/-2.5% higher in the placebo trial and 10.7+/-2.5% higher (P<0.05) in the
      caffeine/ephedra trial; REE was 8.5 +/- 2.0% higher (P<0.05) in the
      caffeine/ephedra trial compared with the placebo trial. Free fatty acids
      increased over time in the placebo and caffeine/ephedra trials (from 0.5+/-0.05
      to 0.63+/-0.05 mEq/L and from 0.48+/-0.06L to 0.8+/-0.05 mEq/L, respectively). 5.
      Caffeine and herbal ephedra, at doses of 150 mg and 20 mg (ephedrine),
      respectively, result in a significant elevation in REE, HR and BP. Although
      significant, the increase in energy expenditure is negligible in terms of weight
      loss.

PMID- 15730435
TI  - Does permanent carotid artery occlusion produce a 'preconditioning-like' effect
      towards more severe hypotension in energy metabolites? Role of cerebral
      adenosine.
AB  - 1. The aim of the present study was to investigate the potential energy
      preserving effect of permanent bilateral common carotid artery occlusion (BCCAO)
      towards additional systemic hypotension of severe duration (30 min). In addition,
      the role of adenosine A1 receptors in cerebral ischaemic preconditioning was
      investigated in male Wistar rats. Thus, oligaemic rats were assigned randomly to
      continuous treatment with the adenosine A1 receptor agonist 2-chloro-N6
      cyclopentyladenosine (CCPA) or the adenosine A1 receptor antagonist 8-cyclopentyl
      1,3-dimethylxanthine (CPT), receiving daily intraperitoneal infusions of 0.1
      mg/kg bodyweight CCPA or CPT or placebo (200 microL aqueous 2-hydropropyl-beta
      cyclodextrin) at a delivery rate of 0.5 microL/h over 14 days. 2. Haemodynamic
      parameters and arterial blood gases were monitored. Rat cortical energy
      metabolites ATP, ADP, AMP, phosphocreatine and adenosine were measured using HPLC
      techniques. Adenosine A1 receptor expression was determined by
      immunhistochemistry and quantified by western blotting. 3. Two weeks of permanent
      BCCAO induced an 'energy saving' effect in rat cortical ATP concentrations. Under
      subchronic conditions, significant increases were detected in ADP and AMP
      concentrations after CCPA compared with placebo. Because similar changes were
      also seen after CPT, this adenosine A1 receptor-mediated effect does not seems to
      be specific. Furthermore, no differences in adenosine A1 receptor expression
      could be detected. 4. Adenosine was not specifically involved in the
      'preconditioning-like' effect via the modulation of the adenosine A1 receptor in
      the present oligaemia model. Obviously, adenosine A1 receptor-specific effects
      after delayed cerebral ischaemic preconditioning do not seem to play an essential
      role if BCCAO is followed by a prolonged additional severe ischaemic event.

PMID- 15730436
TI  - Block of NA+ and K+ currents in rat ventricular myocytes by quinacainol and
      quinidine.
AB  - 1. The electrophysiological actions of quinacainol were investigated on sodium
      (I(Na)), transient outward (i(to)) and sustained-outward plateau (iKsus)
      potassium currents in rat isolated cardiac myocytes using the whole-cell patch
      clamp technique and compared with quinidine. 2. Quinacainol blocked sodium
      currents in a concentration-dependent manner and with a potency similar to that
      of quinidine (mean (+/-SEM) EC50 50+/-12 vs 95+/-25 micromol/L for quinidine and
      quinacainol, respectively). However, quinacainol had a considerably prolonged
      onset and recovery from block compared with quinidine. 3. Neither quinacainol nor
      quinidine significantly changed the steady state voltage dependence of activation
      of sodium currents. Quinidine produced a hyperpolarizing shift in the voltage
      dependence for sodium current inactivation, but no such shift was observed with
      quinacainol at doses that produced a substantial current block. 4. Although
      quinacainol did not effectively block voltage-dependent potassium currents, even
      at concentrations as high as 1.5 mmol/L, quinidine, at a half-maximal sodium
      channel-blocking concentration, reduced peak i(to) current amplitude, increased
      the rate of inactivation of i(to) and blocked iKsus. 5. These results indicate
      that quinacainol, a quinidine analogue, blocks sodium currents in cardiac
      myocytes with little effect on i(to) or iKsus potassium currents, which suggests
      that quinacainol may be exerting class 1c anti-arrhythmic actions.

PMID- 15730437
TI  - Prolongation of the QT interval in primary aldosteronism.
AB  - 1. Only limited information is available concerning the changes in the
      electrocardiogram in primary aldosteronism. The aim of the present study was to
      determine factors influencing the QTc interval in patients with primary
      aldosteronism. 2. Nineteen patients with primary aldosteronism caused by a Conn's
      adenoma and 69 patients with essential hypertension, in whom all possible causes
      of secondary hypertension had been excluded, were included in the present study.
      Before and 10-20 days after adrenalectomy, blood and electrocardiographic
      examinations were conducted. 3. Systolic and diastolic blood pressures in primary
      aldosteronism were found to be comparable to those in essential hypertension.
      However, the QTc interval was significantly prolonged and serum potassium
      concentrations were significantly decreased in patients with primary
      aldosteronism compared with patients with essential hypertension (492.7+/-20.3 vs
      428.5+/-3.1 msec for QTc interval, respectively (P<0.01); 3.07+/-0.12 vs 4.07+/
      0.05 mEq/L for serum potassium concentrations, respectively (P<0.01)). The QTc
      interval was significantly correlated with serum potassium concentrations in
      primary aldosteronism (P=0.0011; r=-0.6902), but not in patients with essential
      hypertension. 4. Blood pressure significantly decreased after adrenalectomy.
      Furthermore, serum potassium concentrations increased significantly and did not
      correlate with the QTc interval after adrenalectomy (P=0.54; r=-0.1500). 5. Our
      results indicate that the QTc interval is prolonged in patients with primary
      aldosteronism, probably owing to hypokalaemia.

PMID- 15730438
TI  - Protective role of tea catechins against oxidation-induced damage of type 2
      diabetic erythrocytes.
AB  - 1. Oxidative stress is recognized as a major contributing factor for the
      development of late complications of diabetes. 2. Tea contains polyphenolic
      compounds (catechins), which have many important biological properties, including
      strong anti-oxidant activity. 3. The present study was undertaken to evaluate the
      effect of tea catechins (epigallocatechin gallate (EGCG), epigallocatechin (EGC),
      epicatechin gallate (ECG) and epicatechin (EC)) on markers of oxidative stress
      (malondialdehyde (MDA), reduced glutathione (GSH) and membrane -SH group) in
      erythrocytes from type 2 diabetics. 4. Oxidative stress was induced in normal and
      type 2 diabetic erythrocytes by incubating with tert-butyl hydroperoxide (t-BHP).
      5. Diabetic erythrocytes have higher MDA and decreased GSH and membrane -SH
      groups compared with normal erythrocytes. 6. Our results show that tea catechins
      protect erythrocytes from t-BHP-induced oxidative stress, the effect being more
      pronounced in diabetic erythrocytes. The relative effectiveness of individual
      catechins are in the order of EGCG>ECG>EGC>EC. 7. We hypothesise that a higher
      intake of catechin-rich food by diabetic patients may provide some protection
      against the development of long-term complications of diabetes.

PMID- 15730439
TI  - Effect of simvastatin given alone and in combination with valsartan or enalapril
      on blood pressure and the structure of mesenteric resistance arteries and the
      basilar artery in the genetically hypertensive rat model.
AB  - 1. The aims of the present study were to investigate, in the New Zealand
      genetically hypertensive (GH) rat model, the effects of treatment with
      simvastatin, alone or in combination with valsartan or enalapril, on blood
      pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA)
      and of the basilar artery, an artery that plays a major role in the regulation of
      cerebral resistance. 2. Genetically hypertensive rats were treated with
      simvastatin at two dose levels (5 and 10 mg/kg per day) and simvastatin in
      combination with valsartan or enalapril (also 5 and 10 mg/kg per day) from the
      age of 7 to 12 weeks. Systolic BP and bodyweight were measured weekly. 3. At the
      end of the experiment, following fixation by perfusion, MRA and the basilar
      artery were excised and embedded in Technovit (a glycol methacrylate medium;
      Heraeus Kulzer, Werheim, Germany). Serial sections were cut and stereological
      techniques used to determine tunica media width and cross-sectional area (CSA),
      lumen diameter and the ratio of media width/lumen diameter. 4. Simvastatin
      monotherapy did not lower BP at either dose. In the high- and low-dose groups,
      the combination of simvastatin + enalapril lowered BP more than with enalapril
      alone; this was also true for the simvastatin + valsartan combination in the
      lower-dose group. 5. The MRA were hypotrophically remodelled by the 10 mg/kg per
      day dose of simvastatin; the 5 mg/kg per day dose caused hypotrophic remodelling
      with decreased media/lumen ratio. Valsartan and enalapril caused hypotrophic
      remodelling together with outward remodelling of the lumen in the 10 mg/kg per
      day valsartan group and, in all groups, a reduction in the media/lumen ratio,
      with the greatest effect observed in the high-dose groups. 6. The combination
      treatments of simvastatin + valsartan and simvastatin + enalapril did not have
      any consistent extra effect on MRA remodelling. 7. In the basilar artery, high
      dose simvastatin had a hypotrophic effect on the media and both doses reduced the
      media/lumen ratio independently of any change in BP. 8. Simvastatin given in
      combination with valsartan produced a slight further reduction in medial CSA,
      media width and ratio. In combination with enalapril, there was little consistent
      additional effect. 9. Simvastatin monotherapy hypotrophically remodelled the
      media of the basilar artery in the GH rat model, even in the absence of changes
      in BP. A similar structural effect may explain, in part, the reduction in stroke
      seen in patients treated with statins.

PMID- 15730440
TI  - Reperfusion injury in the human forearm is mild and not attenuated by short-term
      ischaemic preconditioning.
AB  - 1. Ischaemia-reperfusion (IR) injury is an important contributor to tissue damage
      and has been shown to be attenuated by preconditioning (PC) in some animal
      models. A recent report has suggested that the forearm can be used for the study
      of this phenomenon in humans. We aimed to reproduce and further characterize this
      model. 2. Healthy young adult volunteers (mean (+/-SEM) age 32+/-6 years) were
      studied on two occasions. During one visit, IR alone was induced by 10 min of
      upper arm cuff occlusion, whereas on another occasion a PC stimulus (three 3 min
      cuff inflations) preceded IR. Endothelial function in the ischaemic arm was
      assessed by measuring arterial flow-mediated dilatation (FMD) and by calculation
      of forearm blood flow at baseline and 15 and 60 min after IR. Systemic venous
      blood was sampled from the non-ischaemic arm at baseline, after PC and at 2, 15
      and 30 min after IR to assess neutrophil/leucocyte (CD11b) and platelet (bound
      glycoprotein IIb/IIIa and fibrinogen) activation, as well as numbers of platelet
      leucocyte complexes, which were determined by flow cytometry. Because of a lack
      of measurable effects, the IR experiment was repeated with 20 min ischaemia in
      six subjects. 3. Five females and eight males completed the study. Flow-mediated
      dilatation was significantly impaired 30 min after IR (4.1 vs 6.2% at baseline;
      P<0.05);however, this was not significantly attenuated by ischaemic PC (FMD
      reduction at 30 min compared with baseline was 2.1+/-0.5% with IR alone and 2.6+/
      1.4% with IR after PC; NS). No significant effect was seen on the number of
      platelet-leucocyte aggregates or on white cell or platelet activation after IR
      alone or after IR with PC (P>0.6 for all comparisons). Similar results were
      obtained in six subjects studied subjected to 20 min ischaemia. 4. In conclusion,
      in healthy young adults, brief periods of skeletal muscle ischaemia lead to
      arterial endothelial dysfunction, but no significant platelet or white cell
      activation. Preconditioning does not attenuate this effect on the endothelium.
      Further experiments with longer ischaemia times and varying PC stimuli may be
      necessary to produce measurable effects; however, this may prove difficult in
      conscious human subjects.

PMID- 15730441
TI  - Effect of ultrasonic stimulation on mRNA abundance of uncoupling protein (UCP) 2
      and UCP 3 in gastrocnemius muscle of rats.
AB  - 1. The hypothesis that ultrasonic stimulation upregulates uncoupling protein
      (UCP) 2 and UCP3 in gastrocnemius muscle by a different mechanism of exercise was
      investigated in Wister rats. 2. The ultrasnonic-stimulated group was given
      ultrasonic stimulation to the leg (1 MHz frequency, 1 W/cm2 intensity, 10 min
      continuously). 3. The exercise group was given exercise training by swimming for
      10 min in plastic barrels filled with warm water. 4. After 3 h, rats were killed
      and the gastrocnemius muscle was removed rapidly, weighed and frozen in liquid
      nitrogen for real-time quantitative reverse transcription-polymerase chain
      reaction analysis. 5. In gastrocnenius muscles of ultrasonic-stimulated rats,
      UCP3 mRNA abundance was significantly increased 3.6-fold and UCP2 mRNA abundance
      was significantly increased 2.2-fold compared with control rats. 6. In
      gastrocnenius muscles of exercised rats, UCP3 mRNA abundance was significantly
      increased 3.5-fold compared with control rats, but no change in UCP2 mRNA
      abundance was observed. 7. Plasma free fatty acid (FFA) levels were also
      significantly increased in the ultrasonic stimulation group, as well as the
      exercise group, compared with the control group. 8. These findings show that
      ultrasonic stimulation lipolyses subcutaneous fat into FFA and glycerol and
      upregulates UCP2 and UCP3 mRNA by a mechanism different to that of exercise.

PMID- 15730442
TI  - Introduction: from osseointegration to osseoperception. The functional
      translation.

PMID- 15730443
TI  - Mechanosensory perception: are there contributions from bone-associated
      receptors?
AB  - 1. The identity of the receptors and afferent nerve fibres that mediate the sense
      of touch varies somewhat with body location. Those that have been most
      intensively characterized are associated with the distal glabrous skin of the
      limbs and, in primates, mediate the sense of touch in the fingertips and palms.
      In this glabrous skin region, there appear to be three or four principal classes
      of tactile sensory nerves that fall into two broad groups. One group, the so
      called slowly adapting (SA) receptors and afferent fibres, is responsive to
      static mechanical displacement of skin tissues and is made up of two classes, the
      type I (SAI) fibres that innervate Merkel receptors and the type II (SAII) fibres
      that innervate Ruffini endings. The second broad group displays a pure dynamic
      sensitivity to tactile stimuli and also falls into two principal classes, the
      rapidly adapting (RA) tactile fibres that are associated with Meissner corpuscle
      receptors and the Pacinian corpuscle (PC)-associated class of tactile afferent
      fibres. 2. In other regions of the skin, such as the hairy skin of the arms, legs
      and trunk, there are similar functional classes of tactile sensory nerves,
      although the receptor endings differ somewhat from those of the glabrous skin. 3.
      Receptors in close association with the long bones of the limbs include groups of
      Pacinian corpuscles distributed along the interosseous membranes. These are
      highly sensitive to dynamic forms of mechanical stimuli, in particular
      vibrotactile disturbances. However, despite their close association with bone,
      these receptors probably cannot be legitimately considered 'osseoreceptors'. 4.
      Both the periosteum and the bone marrow are richly supplied by nerve fibres.
      However, much evidence indicates that these are largely or entirely in the fine
      diameter category of nerve fibres, whose roles may be confined to either
      nociception or to the efferent autonomic regulation of bone-associated blood
      vessels. 5. In conclusion, it remains uncertain whether any aspects of our
      innocuous touch or kinaesthetic senses, in either the limbs or in orofacial
      regions, can be ascribed to 'osseoreceptors' located in the periosteum or within
      the bone marrow itself.

PMID- 15730444
TI  - Properties and plasticity of the primate somatosensory and motor cortex related
      to orofacial sensorimotor function.
AB  - 1. The lateral pericentral region of the cerebral cortex has been well documented
      in primates to be important in sensorimotor integration and control and in the
      learning of new motor skills. 2. The present article provides, first, an overview
      of limb sensorimotor cortical mechanisms and, second, outlines recent evidence
      pointing to an important role for the face sensorimotor cortex in semi-automatic,
      as well as trained, orofacial motor behaviour and to its propensity for
      neuroplastic changes in association with orofacial motor skill acquisition or an
      altered oral environment.

PMID- 15730445
TI  - Degree of adaptability of the somatosensory cortex to change: prospects for
      integration of bone-mounted dental prostheses.
AB  - 1. The topographic representation of the body surface in the somatosensory cortex
      provides an important model system for the in vivo study of neuronal plasticity,
      induced changes in somatotopy providing a direct measure of plasticity not
      available in most parts of the central nervous system. 2. Over the past two
      decades, animal experimentation in a number of laboratories has shown a
      remarkable degree of adaptability of the cortical representation following
      peripheral lesions and has had a widespread influence by challenging the once
      accepted dogma that the brain is a structurally fixed organ. 3. Although some
      aspects of original stimulation will be missing, it is likely that receptors
      stimulated through bone conduction and compression by bone-mounted dental
      prostheses preserve some of the geometric and temporal relationships of original
      stimulation. By analogy with data obtained from the forearm representations, it
      would be expected that many features of the original cortical representations
      will be recreated. 4. There are also examples in the literature of perceptual
      learning without gross changes to the cortical representation (some being within
      a class of adaptability known as gain control) and it is likely that perceptual
      integration of many dental prostheses occurs within the limits of these neural
      adaptation mechanisms.

PMID- 15730447
TI  - Oral implant restoration for enhanced oral function.
AB  - 1. The present paper reviews the clinical applications of implant-anchored
      restorations replacing teeth and defects of the craniofacial skeleton resultant
      from congenital, traumatic and surgical tissue loss. 2. Different categories of
      tooth and tissue loss were treated in controlled multicentre prospective clinical
      trials. More recent developments have been the subject of limited pilot studies.
      3. Long-term results and meta-analysis reviews have shown that osseointegrated
      implant-supported restorations were at least equal to, and in some applications
      superior to, traditional treatment methods. 4. Based on the outcome of a 30 year
      research and development programme and validation in numerous clinical trials,
      osseointegrated implant dental rehabilitation has become a viable treatment
      alternative for missing teeth and, for some applications, is considered to be a
      standard of care.

PMID- 15730446
TI  - Sensory and motor function of teeth and dental implants: a basis for
      osseoperception.
AB  - 1. When dental implants are loaded mechanically, a sensation, often referred to
      as osseoperception, is evoked. The sensory signals underlying this phenomenon are
      qualitatively different from the signals evoked when loading a natural tooth. In
      contrast with osseointegrated dental implants, natural teeth are equipped with
      periodontal mechanoreceptors that signal information about tooth loads. In the
      present review, the functional properties of human periodontal mechanoreceptors
      will be presented, along with a discussion about their likely functional role in
      the control of human jaw actions. 2. Microneurographic experiments reveal that
      human periodontal mechanoreceptors adapt slowly to maintained tooth loads.
      Populations of periodontal receptors encode information about both which teeth
      are loaded and the direction of forces applied to individual teeth. 3. Most
      receptors exhibit a markedly curved relationship between discharge rate and force
      amplitude, featuring the highest sensitivity to changes in tooth load at
      surprisingly low forces (below 1 N for anterior teeth and 4 N for posterior
      teeth). Accordingly, periodontal receptors efficiently encode tooth load when
      subjects first contact, hold and gently manipulate food by the teeth. In
      contrast, only a minority of receptors encodes the rapid and strong increase in
      force generated when biting through food. 4. It is concluded that humans use
      periodontal afferent signals to control jaw actions associated with intra-oral
      manipulation of food rather than exertion of jaw power actions. Consequently,
      patients who lack information from periodontal receptors show an impaired fine
      motor control of the mandible.

PMID- 15730448
TI  - Reorganization of the human motor cortex by sensory signals: a selective review.
AB  - 1. The normal human motor cortex can be made to reorganize by repeated
      stimulation of proprioceptive inputs, with or without concurrent stimulation of
      the motor cortex by transcranial magnetic nerve stimulation. Appropriate
      stimulation induces a focal increase in the excitability of corticospinal
      projections to specific muscles and, possibly, an increase in the area of the
      cortex projecting to those muscles. 2. We have shown that repeated stimulation on
      several successive days causes this 'plastic' reorganization to persist for at
      least several days. We have also used this approach to determine whether
      increases in the excitability of the motor cortex can be induced in stroke
      patients (in whom cortical excitability is usually depressed) and whether this is
      accompanied by functional changes. 3. The results of these studies were mixed
      but, in patients in whom plastic changes were induced, there were improvements
      and sometimes marked improvements in both motor function and some
      electrophysiological parameters. The reasons for the inconsistent results are not
      clear, but do not appear to relate to the site, size or nature of the lesion.

PMID- 15730449
TI  - Phantom limb sensation.
AB  - 1. Phantom limb pain and sensations are common in amputees. The present paper
      defines phantom limb pain, stump pain and phantom limb sensation and then gives
      an overview of the incidence and characteristics of the phenomena. 2. Theories of
      phantoms are presented, including peripheral, central and supraspinal theories,
      with particular attention given to Melzack's neuromatrix. 3. Evidence of cortical
      reorganization following amputation is given and the extent to which cortical
      reorganization contributes to phantom limb pain is discussed.

PMID- 15730450
TI  - Physiological characteristics of low-threshold mechanoreceptors in joints, muscle
      and skin in human subjects.
AB  - 1. The development of microneurography, in which an insulated tungsten
      microelectrode is inserted into an accessible peripheral or cranial nerve in
      awake human subjects, has allowed detailed analyses of the signalling capacities
      of single mechanoreceptive afferents from the skin, muscles and joints. For
      example, we know much about how the two classes of rapidly adapting (Meissner and
      Pacinian) and two classes of slowly adapting (Merkel and Ruffini) cutaneous
      mechanoreceptors encode forces applied normal or tangential to the skin of the
      hand and the similarities and differences in glabrous versus non-glabrous skin
      (and receptors associated with hairs). We also know about stretch- and force
      sensitive endings in muscle (the muscle spindle and Golgi tendon organ,
      respectively) and how they behave during passive or active movements or during
      isometric contractions. In addition, we have characterized the firing properties
      of mechanoreceptors in the joint capsules of the fingers. However, we know little
      about sensory nerves in the periosteum, other than that nociceptors and Pacinian
      corpuscles exist. 2. In addition to studies on the physiology of sensory endings
      in human subjects, microstimulation through the recording microelectrode has
      revealed how the brain deals with the sensory information conveyed by a single
      afferent. From this work, we know that there is specificity in the sensory
      channels: electrical stimulation of a single Meissner or Pacinian corpuscle
      generates frequency dependent illusions of 'flutter' or 'vibration', whereas
      microstimulation of a single Merkel afferent can produce a percept of 'pressure'
      and stimulation of a single joint afferent can evoke a sensation of 'joint
      rotation'. Interestingly, the input from a single Ruffini ending in the skin
      cannot be perceived and the same is true of muscle spindle afferents. So, where
      does this leave us with osseoperception from the mouth? Given that the
      periodontal receptors in the vicinity have been lost, which mechanoreceptive
      endings could encode forces applied to a bone-implanted prosthesis? 3. Meissner
      and Merkel endings have very small receptive fields and respond only to local
      forces. Pacinian corpuscles have an exquisite sensitivity to brisk mechanical
      events and could respond to such stimuli transmitted through the bone to a remote
      receptor, but would not be able to encode sustained forces. Ruffini endings also
      respond to forces applied remote to the receptive field and, unlike the Pacinian
      corpuscles, respond in a sustained fashion, but would their signals be perceived?
      Like muscle spindles, it is possible that the coactivation of many Ruffini
      endings could provide meaningful information. Finally, as we have seen, the input
      from a single joint receptor can be perceived, but they mostly respond at the
      limits of joint rotation, so it is unlikely that any associated with the
      temporomandibular joint could contribute to osseoperception.

PMID- 15730451
TI  - A consensus statement on osseoperception.

PMID- 15730452
TI  - Gene expression profiling of breast cancer in ethnic populations: an aid to gene
      discovery for the benefit of all.

PMID- 15730453
TI  - Influence of lactation history on breast nipple aspirate fluid yields and fluid
      composition.
AB  - Analysis of nipple aspirate fluid (NAF) can be useful for understanding the
      impact that various lifestyle factors have on the biology of the breast. In this
      study, breast NAF was obtained at baseline from premenopausal women who
      volunteered for a dietary intervention trial. The influence of lactation history
      on both fluid yields and fluid composition was explored. We examined the levels
      of fat-soluble micronutrients (tocopherols, carotenoids, retinol), one lipid
      oxidation product (8-isoprostane), cholesterol, and protein in NAF. Roughly half
      of the women in the trial had never lactated, but this did not affect fluid
      yields appreciably. Carotenoid and tocopherol levels were significantly higher in
      NAF from women who lactated 6 months or more versus women who had lactated for
      shorter periods of time or never, but 8-isoprostane, protein, and cholesterol
      levels were not affected appreciably by lifetime lactation history. Longer times
      after weaning were associated with higher cholesterol levels, and there also was
      a suggestion the fat-soluble micronutrients declined with time after weaning.
      This is of interest since high cholesterol levels in breast fluid have been
      associated with an increased breast cancer risk, while carotenoids and
      tocopherols are thought to be protective. The results of this study provide
      further evidence of the potential benefits of prolonged lactation via its
      influence on NAF composition.

PMID- 15730454
TI  - Total mastectomy under local anesthesia: the tumescent technique.
AB  - The management of breast cancer in elderly women is controversial. Breast cancer
      in this age group tends to be biologically less aggressive and is highly
      responsive to hormonal intervention. The risk of dying of other causes often
      exceeds the risk of cancer recurrence. For these reasons, older patients tend to
      be treated less aggressively. One large study of elderly women with breast cancer
      found that half of the patients were undertreated. Four patients (mean age 72
      years, range 61-95 years) underwent a unilateral total mastectomy for cancer
      under local anesthesia using the tumescent technique of infiltrating dilute
      lidocaine with epinephrine (25 ml of 1% lidocaine [250 mg] and 1 ml of 1:1000
      epinephrine [1 mg] to 1 L of Ringers lactate) via an infusion pump. Three of the
      patients had estrogen receptor (ER)-negative tumors and one patient had tumor
      progression despite switching from tamoxifen to anastrozole. All four patients
      were class IV as defined by the American Society of Anesthesiology (ASA). There
      was no morbidity related to the surgery in the form of hematoma, wound infection,
      or skin flap necrosis. The patients were discharged 1-4 days after surgery. The
      anesthesia was adequate in all four cases and there was no deviation from the
      described technique. The mean operative time was 35 minutes (range 24-46
      minutes). The tumescent technique is a safe, effective method for performing a
      total mastectomy in patients who would not be considered candidates for general
      anesthesia.

PMID- 15730455
TI  - Implementation of sentinel lymph node biopsy with blue dye outside a specialized
      center: can we improve quality assurance?
AB  - Implementation of sentinel lymph node biopsy (SLNB) outside a specialized center
      requires adequate quality control and quality assurance for optimal patient care.
      We examine the model of a supervising breast cancer unit in improving quality
      assurance in the treatment of breast cancer patients. A total of 76 SLNBs
      followed by level I/II axillary dissection were performed in the general hospital
      by using patent blue V alone. Patient selection, technical information,
      documentation, pathologic examination of the sentinel lymph node (SLN), and
      surgical training were provided by the supervising breast cancer unit. In 73 of
      76 SLNBs, identification of the sentinel node was successful. The false-negative
      rate was 2.7% and the accuracy was 98.6%. The results of the procedure in the
      general hospital were comparable with the results of the supervising breast
      cancer unit. The model of a supervising breast cancer unit seems to accelerate
      surgeons' learning curve and may provide support for appropriate application of
      the SLNB in a wider number of nonspecialized centers.

PMID- 15730456
TI  - Feasibility of surgical management in patients with granulomatous mastitis.
AB  - Granulomatous mastitis (GM) is a rare inflammatory breast disease of unknown
      etiology. Although it usually presents with sinus formation and abscesses, it may
      mimic the clinical characteristics of breast cancer. The aim of this study was to
      identify the clinical, radiologic, and pathologic characteristics of patients
      with GM and to show the results of surgical treatment in these patients. A chart
      review was performed for patients that were treated with a diagnosis of GM at the
      Breast Unit, Department of Surgery, Istanbul Medical Faculty, University of
      Istanbul, between September 1998 and January 2003. Eighteen patients were
      eligible for this study. The median age was 41.5 years (range 16-80 years).
      Seventeen patients were evaluated by both ultrasonography and mammography;
      whereas one young patient only had ultrasonography. Three patients were further
      examined with color Doppler ultrasonography and magnetic resonance imaging (MRI).
      Fourteen patients (78%) presented with a mass as the chief symptom, with a median
      size of 3.9 cm (range 1-8 cm), whereas four patients presented with fistula in
      their breasts. None of the radiologic techniques distinguished benign disease
      from cancer in any of the 14 patients that presented with a mass except one
      patient with normal mammography findings. Ultrasonography was only helpful to
      localize the abscess associated with a fistula tract in one patient. Therefore
      fine-needle aspiration biopsy (FNAB) was performed in six patients, followed by
      surgical excisional biopsy. The remaining eight patients with a clinical
      suspicion of malignancy underwent wide surgical excision with frozen section
      analysis under general anesthesia. All of the FNAB and frozen section evaluations
      revealed benign findings. All of the 18 patients underwent a wide excisional
      biopsy and had a definitive histopathologic diagnosis of GM. The median follow-up
      was 36 months (range 6-60 months). Only one patient had a recurrent disease,
      which was diagnosed at 12 months. GM is a rare breast disease that mimics cancer
      in terms of clinical findings. Preoperative radiologic diagnosis might be
      difficult. Complete surgical excision is the treatment of choice.

PMID- 15730457
TI  - Risk of angiosarcoma following breast conservation: a clinical alert.
AB  - Approximately 100 cases of angiosarcoma following breast-conserving therapy have
      been reported. The prevalence of angiosarcoma following breast conservation has
      not been accurately established and optimal treatment has not been defined. The
      goal of this article is to clarify both issues. The Fisher's exact test was used
      to compare the prevalence of postirradiation angiosarcoma seen in our private
      practice to the prevalence reported from the two largest national database
      studies. A literature review was performed to determine optimal treatment
      guidelines. The results of the comparison indicated that the prevalence of
      postirradiation angiosarcoma seen in our practice was significantly higher than
      that reported in the two national database studies at p-values of 0.0124 and
      0.0080. Also, results from the literature review suggest that early detection and
      aggressive treatment lead to improved outcomes. The data are insufficient to draw
      firm conclusions, but suggest that the current literature underestimates the
      prevalence of angiosarcoma following breast-conserving therapy. Since elderly
      women derive less benefit from radiation and may be more prone to develop
      postirradiation angiosarcoma, confirmation of our findings could lead to a
      reappraisal of the management of elderly patients with early stage breast cancer.

PMID- 15730458
TI  - Race is a fundamental prognostic indicator for 2325 northeastern Ohio women with
      infiltrating breast cancer.
AB  - The goal of this research was to determine if race, independent of socioeconomic
      status, is a prognostic indicator for women diagnosed with infiltrating breast
      cancer. We hypothesized that black patients would present with breast cancers
      having less favorable prognostic indicators relative to white patients,
      regardless of socioeconomic status. Using data collected prospectively in our
      institutional review board approved breast center patient registry and 2000
      Census Tract data for northeastern Ohio, we compared tumor size, node status,
      hormone receptor status, clinical outcomes, and socioeconomic status for patients
      who were self-described as either black or white and who had been diagnosed with
      infiltrating breast cancer. The chi-square test, t-test, log-rank test, and Cox
      proportional hazards analysis were used to analyze the data. Kaplan-Meier outcome
      curves were generated. Data were available for 2325 women, including 313 who were
      black and 2012 who were white. Compared to white patients, black patients were
      more likely to have positive axillary nodes and to have hormone receptor-negative
      tumors. Black patients were also more likely to have positive axillary nodes
      associated with smaller tumors. Independent of socioeconomic status, black
      patients were more likely to have poorer overall survival and disease-free
      survival rates for breast cancer relative to white patients. The prognostic
      significance of race was not dependent on a concomitant relationship with
      socioeconomic status.

PMID- 15730459
TI  - Excision only for tubular carcinoma of the breast.
AB  - The purpose of this study was to assess the rationale of excision only (without
      breast irradiation) in patients with small (< or =3 cm) tubular/well
      differentiated breast cancers. A total of 44 patients with pure tubular invasive
      breast cancer who have undergone complete excision only and have had a minimum 1
      year follow-up were identified from the Colorado Cancer Registry and assessed for
      recurrence rates as well as median local disease-free and overall survival.
      Treatment dates were October 1972 to April 2001. The median age was 67 years
      (range 40-96 years). The median tumor size was 6.5 mm (range 2-30 mm). All
      patients had a complete excision with negative margins. Staging was as follows:
      T1N0 (11), T1Nx (27), T2N0 (1), T1N1 (3); 2 were unable to be staged accurately.
      After a median follow-up of 5.4 years (range 1.1-26.3 years) there were only two
      local recurrences in the ipsilateral breast (at 7.6 and 8.8 years), for a crude
      local control rate of 96% (2/44). Both patients were salvaged, are alive, and
      currently have no evidence of disease (NED) at last follow-up of 9 and 13.3
      years. Actuarial 5- and 10-year local control rates were 100% and 87%. Actuarial
      5- and 10-year overall and disease-free survivals were 80% and 52%, and 100% and
      91%. Twenty-five patients had more than 5 years of follow-up. The median follow
      up for this group was 9.1 years (range 5.1-26.3 years) and both recurrences were
      in this group. Although the number of cases in this report is small, it
      represents the largest total and longest follow-up for tubular breast cancer
      cases after excision alone. This report suggests that breast irradiation could be
      omitted after conservative surgery in older patients with smaller (< or =3 cm)
      tubular/well-differentiated breast cancers. However, due to the retrospective
      nature of our report, we cannot categorically make this recommendation.

PMID- 15730460
TI  - Breast cancer pseudometastasis in a sentinel lymph node with cytokeratin-positive
      debris.
AB  - We report extensive pseudometastasis detected by immunohistochemical (IHC)
      staining within a sentinel lymph node. An 83-year-old woman underwent simple
      mastectomy and sentinel lymph node biopsy (SLNB) for infiltrating ductal
      carcinoma. Intraoperative frozen section of the SLNB specimen appeared
      histologically negative for metastasis. IHC staining for cytokeratin in permanent
      sections, however, showed what was reported as micrometastasis in the subcapsular
      sinus. Since these cells did not resemble the primary tumor cells
      morphologically, and had actually been called histiocytes in the frozen section,
      further IHC staining was done. The subcapsular cells were negative for epithelial
      membrane antigen (EMA) staining, but they were positive for CD68, a macrophage
      marker. Thus the cytokeratin-positive cells were not metastatic breast tumor
      cells, but rather were histiocytes with phagocytized cytokeratin debris. This
      case report illustrates that IHC staining for cytokeratin in SLNB specimens for
      breast cancer must be supported by morphologic assessment and further appropriate
      staining before it can become the basis for treatment decisions.

PMID- 15730461
TI  - Triad of columnar cell alteration, lobular carcinoma in situ, and tubular
      carcinoma of the breast.
AB  - Columnar cell alteration in the breast encompasses a spectrum of pathologic
      changes ranging from simple columnar cell change to more complex columnar cell
      hyperplasia with and without atypia to in situ carcinoma, often with a
      micropapillary architecture. For reasons that remain unclear, the columnar cell
      lesions are associated with tubular carcinomas and lobular carcinoma in situ.
      Therefore it is important to be familiar with the spectrum of changes and the
      associated lesions, especially in breast core biopsies for further management.

PMID- 15730462
TI  - Metastatic breast cancer to the bladder.

PMID- 15730463
TI  - Phyllodes tumor of the breast: magnetic resonance imaging findings and surgical
      treatment.

PMID- 15730464
TI  - Malignant cystosarcoma phyllodes of the breast treated with oncoplastic
      conservative surgery.

PMID- 15730465
TI  - Chondrosarcoma of the breast.

PMID- 15730466
TI  - Basal cell carcinoma of the skin presenting as microcalcifications on screening
      mammography.

PMID- 15730468
TI  - Abandoned advanced breast cancer in an old patient: a difficult challenge.

PMID- 15730467
TI  - Microcalcifications of pectoral muscle in trichinosis.

PMID- 15730469
TI  - Synchronous bilateral breast cancer in an elderly man.

PMID- 15730470
TI  - Sentinel lymph node biopsy in ductal carcinoma in situ of the male breast.

PMID- 15730471
TI  - Accessory breasts: when to excise?

PMID- 15730472
TI  - Management of metastatic melanoma to the breast with high-dose interleukin-2 and
      surgical resection.

PMID- 15730473
TI  - A tail of two axillae.

PMID- 15730474
TI  - A report of a breast cancer cluster among employees of an elementary school.

PMID- 15730476
TI  - The salmon vertebral body develops through mineralization of two preformed
      tissues that are encompassed by two layers of bone.
AB  - The teleost backbone consists of amphicoelous vertebrae and intervertebral
      ligaments, both of which include notochord-derived structures. On the basis of a
      sequential developmental study of the vertebral column of Atlantic salmon (Salmo
      salar L.) from the egg stage up to early fry stage (300-2500 day-degrees) we show
      that the vertebral body consists of four layers or compartments, two of which are
      formed through mineralization of preformed collagenous tissue (the notochordal
      sheath and the intervertebral ligament) and two of which are formed through
      ossification. The three inner layers have ordered lamellar collagen matrixes,
      which alternate perpendicularly from layer to layer, whereas the outer layer
      consists of cancellous bone with a woven matrix. The bone layers also differ in
      osteocyte content. In this study we describe the structural details of the
      layers, and their modes of formation. The results are compared with previous
      descriptions, and possible phylogenetic implications are discussed.

PMID- 15730477
TI  - Regional variation of intracortical porosity in the midshaft of the human femur:
      age and sex differences.
AB  - This study investigated age and sex differences in patterns of porosity
      distribution in the midshaft of the human femur. Cross-sections were obtained
      from 168 individuals from a modern Australian population. The sample comprised 73
      females and 95 males, aged between 20 and 97 years. Microradiographs were made of
      100-microm sections and pore and bone areas were determined using image
      processing software. Initially the sample was divided by age: young (20-44
      years), middle (45-64 years) and old (65+ years), but it was found that analysis
      on the basis of the ratio of medullary area to total subperiosteal area gave
      clearer results. The cortex was divided into three rings radially and into
      octants circumferentially and the porosity of each segment was calculated.
      Results showed that a pattern with raised porosity in the posterior and
      anterolateral regions, and with greater porosity in the inner parts of the
      cortex, becomes more pronounced with age. In males this pattern develops
      steadily; in females there are much greater differences between the middle and
      older groups than earlier in life. The patterns observed are consistent with
      progressive bone loss occurring along a neutral axis of the cortex where bending
      stress is lowest and the mechanical advantage of the bone is least.

PMID- 15730478
TI  - Relationships among microstructural properties of bone at the human midshaft
      femur.
AB  - Mineralization density and collagen fibre orientation are two aspects of a bone's
      microstructural organization that influence its mechanical properties. Previous
      studies by our group have demonstrated a distinctly non-random, though highly
      variable, spatial distribution of these two variables in the human femoral
      cortex. In this study of 37 specimens, these variables are examined relative to
      one another in order to determine whether regions of bone demonstrating higher or
      lower mineralization density also demonstrate a prevalence of either transversely
      or longitudinally oriented collagen fibres. An analysis of rank-transformed
      collagen fibre orientation (as determined by circularly polarized light) and
      mineralization density (as determined by backscattered electron microscopy) data
      sets demonstrated that areas of low mineralization density (predominantly in the
      anterior-lateral cortex) tended to correspond to regions of higher proportions of
      longitudinally oriented collagen fibres. Conversely, areas of higher
      mineralization density (postero-medially) tended to correspond to regions of
      higher proportions of transversely oriented collagen fibres. High variability in
      the sample led to generally low correlations between the two data sets, however.
      A second analysis focused only on the orientation of collagen fibres within
      poorly mineralized bone (representing bone that was newly formed). This analysis
      demonstrated a lower proportion of transverse collagen fibres in newly formed
      bone with age, along with some significant regional differences in the prevalence
      of collagen fibres of either orientation. Again high variability characterized
      the sample. These results are discussed relative to the hypothesized forces
      experienced at the midshaft femur.

PMID- 15730479
TI  - Sexually dimorphic proportions of the harbour porpoise (Phocoena phocoena)
      skeleton.
AB  - Sexual differences in growth, allometric growth patterns and skeletal proportions
      were investigated by linear measurements of skeletal parts on 225 harbour
      porpoises (Phocoena phocoena) from the inner Danish and adjacent waters. Females
      show larger asymptotic sizes and extended period of growth compared with males.
      Measurements of the skull and flipper bones show negative allometry, whereas
      those of the bones of the body generally show positive allometry. There are no
      statistically significant intersexual differences in allometry except for the
      pelvic bones, where the males show stronger positive allometry. Throughout the
      range of individual sizes, females have significantly larger skulls and shorter
      vertebral columns than males for similarly sized individuals. In fully grown
      specimens, the condylobasal length of females makes up a smaller proportion of
      total length, and the vertebrae make up a larger proportion as compared with
      males. As these characters show negative and positive allometry, respectively, it
      is suggested that males finish their development at an earlier stage than
      females, retaining more paedomorphic proportions of the skeleton. Paedomorphosis
      in fully grown males relative to females is also found in the vertebral epiphyses
      that mature later in males than females, although the males finish growth at a
      younger age.

PMID- 15730480
TI  - Morphogenesis of the juxtaoral organ in humans.
AB  - The juxtaoral organ was studied using light microscopy in 55 human embryos and 90
      fetuses at different stages of development. The juxtaoral organ arises from the
      epithelium at the bottom of the transverse opening of the primitive mouth during
      O'Rahilly stage 16 and becomes detached from the epithelium after O'Rahilly stage
      18. The juxtaoral organ is innervated by the buccal nerve from O'Rahilly stage 20
      onward, and its connective tissue capsule is clearly visible after week 11 of
      development. This study enabled us to describe three main periods of juxtaoral
      organ development: (1) the period of epithelial condensation and invagination, at
      O'Rahilly stages 16-17; (2) the period during which the juxtaoral organ becomes
      detached from the oral epithelium and is innervated, at O'Rahilly stages 18-23;
      and (3) the period during which the connective tissue capsule is formed, after
      week 11 of development. We also analysed the juxtaoral organ of five additional
      fetuses by immunohistochemistry with anti-NF-200 to verify their innervation. The
      results show that the juxtaoral organ may have a function in the mechanical
      activity of the region.

PMID- 15730481
TI  - beta-Catenin expression during vascular development and degeneration of avian
      mesonephros.
AB  - beta-Catenin is a structural component of adherens junctions, a regulator of the
      Wnt signalling pathway and a transcriptional co-activator with a key role in
      vascular patterning. The avian mesonephros is a transitory embryonic kidney that
      is used in the study of vascular development and degeneration. Here we examine
      beta-catenin expression in this model during vascular development and
      degeneration. Quail embryos with developing or degenerating mesonephros were
      studied, on day 6 (30HH) or day 11 of incubation (40HH), respectively. QH1 whole
      mounts of developing mesonephros revealed numerous angioblast-like cells situated
      in the paramesonephric duct that seem to invade the mesonephros. Although these
      cells did not express beta-catenin, the surrounding periductal mesenchymal cells
      translocated high levels of beta-catenin into the nucleus. In contrast,
      degenerating mesonephros were devoid of angioblast-like cells and beta-catenin
      was lower than in the developing mesonephros. beta-Catenin was significantly
      reduced in the glomerular capillary tuffs, indicating that it was particularly
      down-regulated in the vascular system. No sex-related differences in beta-catenin
      expression were observed in degenerating mesonephros. Furthermore, two special
      populations of glomerular and peritubular endothelial cells were observed in
      degenerating mesonephros: one translocating beta-catenin into the nucleus and the
      other in apoptosis that did not translocate it. In conclusion, our results
      indicate that the paramesonephric duct is a potential new vasculogenetic pathway,
      and suggest that beta-catenin plays a role in the fate of mesonephric endothelial
      cells.

PMID- 15730482
TI  - Effects of glial cell line-derived neurotrophic factor on isolated developing
      mouse Sertoli cells in vitro.
AB  - Cell proliferation is a key factor in sex determination where a size increase
      relative to the XX gonad is one of the first signs of testis differentiation.
      Moreover, proliferation of Sertoli cells during development is important in
      building up the stock of supporting cells necessary for subsequent successful
      fertility. Because proliferation is such an essential part of testis development,
      the hypothesis under long-term investigation is that it is under fail-safe
      control by multiple alternative growth factors. This study was undertaken to
      investigate the role of glial cell-derived neurotrophic factor (GDNF) on
      developing mouse Sertoli cells in vitro. Sertoli cells, isolated from mouse
      embryos at three stages of testis development, were maintained for 2-7 days in
      vitro (div) in the presence or absence of GDNF at 1, 10 and 100 ng mL(-1).
      Overall the presence of extracellular matrix gel had little effect on
      proliferative activity, but encouraged expression of the epithelial phenotype. A
      statistically significant difference in proliferation, assessed by
      immunocytochemical staining for proliferating cell nuclear antigen, was seen with
      GDNF at embryonic day (E)12.5 after 2 div (at both 10 and 100 ng mL(-1), P <
      0.001) and 7 div (at both 10 and 100 ng mL(-1), P < 0.05); at E13.5 after 3 div
      (at both 10 and 100 ng mL(-1), P < 0.05) and at E14.5 after 7 div (100 ng mL(-1),
      P < 0.01), compared with controls cultured without growth factor. In conclusion,
      GDNF stimulates mitosis throughout this critical developmental window. The in
      vitro approach used here is a useful adjunct to the knockout mouse model and has
      been applied to show that GDNF exerts a proliferative effect on developing mouse
      Sertoli cells.

PMID- 15730483
TI  - Correlation between volume fraction and volume-weighted mean volume, and between
      total number and total mass of islets in post-weaning and young Wistar rats.
AB  - The aim of this study was to estimate the number and volume distribution of
      islets of Langerhans in post-weaning young Wistar rat pancreas and their
      variation with age. Four groups of six normal Wistar Kyoto rats, at 3, 6, 9 and
      12 weeks of age, were used. The whole pancreas was weighed (W), fixed in buffered
      formaldehyde and embedded in JB4 resin, and 1.5-microm serial sections were
      obtained. A fraction of whole tissue was obtained in accordance with the
      multistage fractionator principle and used to estimate total number of islets
      (N(is)). Volume fraction (V(f)) of islets and volume-weighted mean volume (Vv) of
      islets were estimated using point-counting and point-sampled intercept methods,
      respectively. The numbers of islets increased steadily with age (P < 0.001),
      whereas the volume-weighted mean volume of individual islets was not
      significantly different among all age groups of rats (P > 0.05). There was a
      strong positive correlation between total islet number and islet mass (r = 0.96,
      P = 0.001), and between volume fraction and islet mass (r = 0.969, P = 0.001).
      However, there was a weak positive correlation between volume fraction and volume
      weighted mean islet volume (r = 0.6, P = 0.002) in the age window investigated.
      These findings indicate that there was an increase in the number and volume
      fraction of islets with age in post-weaning young rats but that individual islet
      volume did not change significantly. It appears the mechanism of alteration in
      islet morphology in the rat is mainly by the formation of new islets while
      keeping their individual volume distribution unchanged.

PMID- 15730485
TI  - Clinical application of sirolimus in renal transplantation: an update.
AB  - In addition to an analysis of the final results of phase I/II and phase III
      clinical trials of sirolimus (SRL), this review focuses on the recent results of
      several studies in renal transplantation, which include diverse combinations of
      SRL with other immunosuppressive agents. While SRL was initially introduced as an
      adjunctive agent to calcineurin inhibitors, it is now serving as the base for
      therapies that spare or avoid these nephrotoxic drugs. However, to optimize the
      use of SRL as base therapy, further work is necessary to determine target
      concentrations, requirement for concomitant steroids and/or nucleoside synthesis
      blockers, and countermeasure therapy to overcome the drug's adverse effects.

PMID- 15730484
TI  - The role of the extrinsic thoracic limb muscles in equine locomotion.
AB  - Muscles have two major roles in locomotion: to generate force and to
      absorb/generate power (do work). Economical force generation is achieved by short
      fibred pennate muscle while the maximum power output of a muscle is architecture
      independent. In this study we tested the hypothesis that there is an anatomical
      and structural separation between the force-generating anti-gravity muscles and
      the propulsive (limb/trunk moving) muscles of the equine forelimb. Muscle mass
      and fascicle length measurements were made on the thoracic limb extrinsic muscles
      of six fresh horse cadavers. Physiological cross-sectional area and maximum
      isometric force were then estimated. Maximum power was estimated from muscle
      volume and published contraction velocity data. The majority of extrinsic
      forelimb muscles were large with long fascicles arranged in parallel to the long
      axis of the muscle. Muscles arranged in this way are optimised for doing work.
      The architecture of serratus ventralis thoracis (SVT) was unique. It had short
      (48 +/- 17 mm) fascicles, arranged at about 45 degrees to the long axis of the
      muscle, which would suggest a force-generating, anti-gravity role. The muscle
      belly of SVT was sandwiched between two broad, thick sheets of aponeurosis.
      Hence, SVT could make a significant contribution to the overall elastic
      properties of the thoracic limb.

PMID- 15730486
TI  - Liver transplantation in hepatocellular carcinoma.
AB  - Liver transplantation is one option of surgical treatment for cirrhotic patients
      with hepatocellular carcinoma, it not only treats the malignancy but also the
      underlying disease. After an initial period of disappointing results, mainly due
      to lack of adequate selection, survival nowadays is similar to that obtained by
      cirrhotic patients without tumor. Currently the scarcity of donors is the main
      limitation in the treatment of this type of patients. Increased time on the
      waiting list does compromise the results if they are analyzed in an intention-to
      treat basis. Adjuvant therapy on the waiting list (ethanol injection,
      chemoembolization, surgery, etc.) or the use of marginal grafts in order to
      increase the donor pool may be some alternatives to overcome this deficit. The
      development of adult living donor liver transplantation has proved to be a good
      alternative in this type of patients even if they do not fulfill the conventional
      criteria.

PMID- 15730487
TI  - Low incidence of malignancy after transplantation in Chinese heart allograft
      recipients.
AB  - This study sought to assess the incidence of neoplastic disease after
      transplantation in Chinese heart allograft recipients. A total of 156 patients
      (130 male and 26 female; mean age, 45.8 +/- 15.7 years), surviving more than 30
      days after transplantation, were enrolled in this study. The mean follow up
      duration was 51.2 +/- 33.0 months. Six patients (3.8%) developed neoplastic
      diseases after transplantation: post-transplant lymphoproliferative diseases in
      four and solid tumors in two patients. There was no skin cancer or Kaposi's
      sarcoma. Solid tumors affected the prostate, liver and urinary bladder in two
      patients. The cumulative incidence of neoplastic disease was 2.1% at 1 year, 3.6%
      at 5 years, and 10.1% at 10 years after transplantation. The incidence of post
      transplant neoplastic disease was low in Chinese heart allograft recipients. It
      resulted from a relative paucity of Kaposi's sarcoma and skin cancers in Chinese
      population.

PMID- 15730488
TI  - Cyclosporin and tacrolimus increase plasma levels of adenosine in kidney
      transplanted patients.
AB  - The immunosuppressive agents, cyclosporin (CsA) and tacrolimus (FK506), display
      cardioprotective activities. The mechanism would consist on the inhibition of the
      enzyme, adenosine kinase (AK), leading to an increase in adenosine (ADO) levels.
      ADO, inosine (INO) and nucleotide plasma levels were measured in kidney
      transplant recipients before and 1, 2, 4, 6 and 8 h after the administration of
      CsA or FK506. After CsA and FK506 administration, ADO plasma levels significantly
      increased, reaching a peak level after 2 h (483 +/- 124 and 429 +/- 96 nm,
      respectively), and then progressively declined. Calculated peak values (t(max))
      of ADO were slightly delayed with respect to those of CsA and FK506. Treatment
      with rapamycin did not influence the phenomenon. The dynamic profile of plasma
      changes of ADO, nucleotides and INO were consistent with the inhibition of the
      enzyme, AK. ADO increase may be clinically relevant in terms of anti-ischaemic,
      tissue protecting, and immunosuppressive activities as well as in terms of
      nephrotoxicity.

PMID- 15730489
TI  - Gastrointestinal bleeding from enterically drained transplanted pancreas.
AB  - Gastrointestinal bleeding has been described as related complication of pancreas
      transplantation. Of 166 simultaneous pancreas kidney transplantations, 61 were
      enteric-drained pancreas transplants (eight done with and 53 without Roux-en-Y
      loop). The patients were divided into two groups according to Roux (group I, n =
      8) or no Roux (group II, n = 53) technique. Seven patients experienced
      anastomotic hemorrhage between the jejunum and duodenal stump (11%), five cases
      in group I and two in group II (P < 0.001). No relationships between
      gastrointestinal bleeding duodenal stump and recipient jejunum blood flow, mean
      pancreatic cold ischemia time, platelet count, and prothrombin time were
      observed. Donor age over 40 years and abnormal activated partial thromboplastin
      time constituted risk factors for hemorrhage from the duodenojejunal anastomosis.
      There were no significant differences in pancreas graft and patient survival
      rates between the two groups. Anastomotic hemorrhage did not influence patient
      and graft survival.

PMID- 15730490
TI  - Abnormal total ejection isovolume index as early noninvasive marker of chronic
      rejection in heart transplantation.
AB  - Abnormally high myocardial performance index (MPI) is a Doppler-derived marker of
      combined systolic and diastolic left ventricular (LV) dysfunction. To identify
      early stage allograft dysfunction by MPI, we studied 154 long-term heart
      transplantation (HT) recipients (131 male, aged 51 +/- 13 years at HT, mean
      follow up 8.4 +/- 3.5 years), with normal left ventricular ejection fraction
      (LVEF) and free from acute rejection (AR), and 25 normals (13 male, aged 39 +/-
      16 years). Rejection score (RS) on endomyocardial biopsy was calculated in the
      first year. MPI was prolonged (0.45 +/- 0.18 vs. 0.28 +/- 0.10, P = 0.0001) in
      patients and directly related with mean time from HT (P = 0.001), higher
      cumulative dosages of cyclosporine at 3 months (P = 0.01), 6 months (P = 0.03), 1
      year (P = 0.02), 3 years (P = 0.04) and with cumulative dosage of
      methylprednisolone at 1 year (P = 0.002). The index was inversely related with
      mean age at HT (P = 0.002) and tended to be directly related with RS at 1 year (P
      = 0.05). Thus, MPI is abnormal in long-term HT recipients with normal LVEF. Its
      direct relation with time from HT as well as immunosuppressive load suggests an
      early stage of graft dysfunction because of chronic rejection. Extended
      prospective studies are warranted to clarify its potential role as a negative
      prognostic marker in HT.

PMID- 15730491
TI  - Post-transplant diabetes mellitus: a case-control analysis of the risk factors.
AB  - Aim of the present study was to assess, in a pair-matched analysis design, risk
      factors for post-transplant diabetes mellitus (PTDM) in renal transplant
      recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx in
      relation to their baseline immunosuppression. PTDM was defined according to the
      2003 American Diabetes Association and World Health Organization experts
      committee definition. As risk factors for PTDM development were considered: age,
      family history of diabetes, body mass index (BMI), baseline immunosuppression,
      doses and blood levels of the immunosuppressive agents used. Baseline
      immunosuppression consisted of CSA, TAC and SRL + CNI. Thirty-two pair-matched
      controls were identified among the 538 KTx and included in the risk analysis.
      Significant risk factors for the development of PTDM were identified in the
      family history of diabetes (P < 0.02) and BMI (P < 0.05). Higher BMI and positive
      family history for diabetes mellitus were significant risk factors for the
      development of PTDM, regardless of the immunosuppressive agent used.

PMID- 15730492
TI  - Capillary deposition of the complement fragment C4d in cardiac allograft biopsies
      is associated with allograft vasculopathy.
AB  - Cardiac allograft vasculopathy (CAV) is a long-term threat in heart transplant
      recipients and its exact pathogenesis remains to be established. As complement
      activation contributes to early and late allograft dysfunction, we hypothesized
      that deposition of the complement fragment, C4d, in capillaries of cardiac
      allograft biopsies may be associated with CAV. A polyclonal anti-C4d antibody was
      used for immunohistochemistry on endomyocardial biopsies obtained from heart
      transplant recipients during the first year post-transplantation. CAV was
      assessed by intracoronary ultrasound performed at 1-year post-transplantation. We
      were able to show that CAV is highly associated with C4d deposition in
      capillaries of cardiac allografts and that serial C4d studies may predict
      development of CAV at 1-year post-transplantation.

PMID- 15730493
TI  - Venous outflow reconstructions with the piggyback technique in liver
      transplantation: a single-center experience of 431 cases.
AB  - The ideal method of venous outflow reconstruction with the piggyback technique
      (PB) in orthotopic liver transplantation (OLT) is not well-established. The
      complications related to PB in 431 primary OLTs were analyzed comparing the
      orifices used for the anastomosis (cuff of the recipient left and middle hepatic
      veins [LM], LM with a >1 cm cavoplasty [LM+], or also including the right hepatic
      vein [LMR]). Treatment strategies and outcome were also evaluated. Twenty
      patients (4.6%) experienced complications: 13 of 120 (10.8%) with LM, four of 225
      (1.8%) with LM+, and three of 86 (3.5%) with LMR (LM versus LM+: P < 0.0001; LM
      versus LMR: P = NS; LM+ versus LMR = NS). Balloon dilation was successful in 10
      of 13 cases in which it was attempted (77%). Eight patients required
      retransplantation (40%). Three patients (0.7%) died from causes linked to
      stenosis. Five-year survival of patients with and without complications was 75%
      and 79%, respectively (P =NS); 5-year graft survival was 50% and 76%,
      respectively (P = 0.001). The stump formed by the recipient left and middle
      hepatic veins with a transversal incision >1 cm of the caval wall constantly
      provides an adequate width for the caval anastomosis with the PB.

PMID- 15730494
TI  - Severe right heart failure after heart transplantation. A single-center
      experience.
AB  - We reviewed our heart transplantation recipient population, using hard criteria
      defining severe right heart failure (RHF), and analyzed possible risk factors for
      outcome after RHF. Between 1983 and 1998 621 cardiac transplantations were
      performed at our institution. RHF was defined by the necessity to implant an
      assist device or echocardiographically confirmed right ventricular ballooning
      with concomitant end organ failure. RHF patients were compared with a matched
      control group. Thirty-five patients (5.9%) with severe RHF after transplantation
      fulfilled inclusion criteria. Of these, 32 patients died, while none of the
      control patients died (P < 0.001). Increased preoperative pulmonary capillary
      wedge (P = 0.005) and mean pulmonary artery pressure (P = 0.006) were identified
      as significant risk factors for severe RHF. Severe RHF as defined in our study is
      irreversible in almost every case without differences among therapeutical
      concepts. Hence, improvement of postoperative outcome necessitates avoidance or
      aggressive therapy of possible risk factors.

PMID- 15730495
TI  - Expression of adhesion molecules and RANTES in kidney transplant from nonheart
      beating donors.
AB  - The main difference between cadaveric kidneys from donors with a heartbeat (HBD)
      and kidneys from nonheart-beating donors (NHBD) is related to warm
      ischemia/reperfusion time which constitutes an acute inflammatory process. On the
      contrary, brain death induces in HBD expression of pro-inflammatory adhesion
      molecules, making it important to evaluate this kind of molecules in both types
      of donors. Human renal biopsies from NHBD, HBD and normal kidneys (ischemia time
      = 0) were taken and frozen just before transplant. A semi-quantitative RT-PCR
      method was used to determine intracellular adhesion molecule 1 (ICAM-1), vascular
      cell adhesion molecule 1 (VCAM-1), lymphocyte function associated antigen (LFA
      1), LFA-3, CD40, CD40 ligand (CD40L) and RANTES (regulated upon activation,
      normal T-cell expressed and secreted) gene expression. We have detected an
      elevated relative gene expression of ICAM-1, VCAM-1 and RANTES in NHBD biopsies
      compared with normal kidneys. In the case of RANTES, the gene expression from
      NHBD biopsies was higher than observed in HBD biopsies. The rest of genes were
      not augmented in any group. Preliminary data about early outcome of transplants
      indicates a correlation between pretransplant RANTES high gene expression levels
      and early post-transplant acute rejection. The gene expression of pro
      inflammatory molecules like adhesion molecules and RANTES is augmented in kidneys
      from cadaveric NBD just before transplant. The expression is higher probably
      because of the prolonged warm ischemia period. A larger clinical study is
      necessary to clarify the effects of these variable expressions on the transplant
      outcome.

PMID- 15730496
TI  - Peritransplant treatment with cobalt protoporphyrin attenuates chronic renal
      allograft rejection.
AB  - Allogen-independent injury contributes to chronic rejection in renal allografts
      and heme oxygenase-1 (HO-1) has been shown to be protective in a number of
      settings. This study evaluated the effect of renal allograft recipient HO-1 up
      regulation on chronic rejection in a rat model. Rat (F344 to Lewis) renal
      transplantation recipients were grouped: (i) cyclosporine (CsA) alone (0.75 mg/kg
      s.c. x 10 day; n = 5); (ii) CsA + low dose cobalt protoporphyrin (CoPP) an HO-1
      inducer (0.5 mg/kg i.p. on days -5,0,5; n = 13) and (iii) CsA + high dose CoPP
      (5.0 mg/kg i.p. on days -5,0,5; n = 8). Renal function was assessed by serum
      creatinine levels on day 140. Histopathologic changes in allografts were graded.
      Morphometric analyses performed to objectively quantify the vascular changes and
      glomerulosclerosis. HO-1 expression quantified by Western blot and both HO-1 and
      endothelin (ET-1) localized using immunohistochemistry. Recipients treated with
      CsA + high dose CoPP had significantly decreased cortical scarring, vascular
      hyalinization and intimal thickness. They also had a significant, dose-dependent,
      reduction in luminal obliteration and glomerulosclerosis by morphometric
      analyses. This freedom from chronic rejection in recipients treated with CoPP
      translated into quiescent grafts at postoperative day 140 with immunostaining and
      Western blot demonstrating decreased level of HO-1 versus controls (P = 0.012).
      In summary, the peritransplant up-regulation of HO-1 in renal allograft
      recipients significantly attenuates chronic rejection in rat renal allografts by
      inhibiting transplant vasculopathy.

PMID- 15730497
TI  - Gastroduodenal artery steal syndrome during liver transplantation: intraoperative
      diagnosis with Doppler ultrasound and management.
AB  - Arterial steal syndrome (ASS) after liver transplantation has been reported. ASS
      causes arterial hypo-perfusion of the graft liver and devastating consequences.
      However, the diagnosis tends to be delayed. We present the recognized case of a
      gastroduodenal artery (GDA) steal syndrome that was diagnosed with intraoperative
      Doppler ultrasound and treated with GDA ligation during the liver
      transplantation. The patient had variation of hepatic artery anatomy (low
      bifurcation of the hepatic artery). Graft liver had the common hepatic artery and
      aberrant left hepatic artery. Doppler ultrasound of the liver was performed after
      the arterial reconstruction between the donor common hepatic artery and recipient
      right hepatic artery. It showed low hepatic arterial flow. There is no backflow
      bleeding from the donor aberrant left hepatic artery stump. After ligating big
      GDA, hepatic arterial waveform inside the liver drastically improved and strong
      backflow bleeding was recognized from the donor left aberrant hepatic artery
      stump. The current case should show the efficacy of intraoperative Doppler
      ultrasound of the liver on ASS and alert clinician to ligate GDA to prevent ASS
      if hepatic arterial flows are suboptimal.

PMID- 15730498
TI  - Sirolimus quantification by high-performance liquid chromatography with
      ultraviolet detection.
AB  - The need to adapt optimal conditions of sirolimus blood level monitoring in
      laboratories led us to optimize an high-performance liquid chromatography
      ultraviolet method and compare the elution performances using the mobile phase A,
      68% MeOH/2% acetonitrile (ACN)/30% H(2)O and mobile phase B, 30% MeOH/42% ACN/28%
      H(2)O. Samples were assayed with 1-chlorobutane, redissolved in MeOH/water and
      injected onto a C-18 column at 50 degrees C. The assay achieved sensitivity of
      2.5-150 ng/ml (CV = 10.6%) and recovery of 92-103.6%. The intra- and interassay
      precisions ranged from 3.3% to 13% and from 5.9% to 15% for quality controls of
      7.5, 60 and 120 ng/ml. The mobile phase A was unable to elute and recover
      sirolimus and internal standard in the expected retention time and concentration.
      Under our working conditions, the assay was precise, accurate and sensible,
      stressing the importance of establishing for the best working conditions
      according to the staff and demands of the laboratory.

PMID- 15730499
TI  - Skin disorders in patients transplanted in childhood.
AB  - Only few data are available on skin disorders in pediatric organ transplant
      recipients. In order to describe the whole range of dermatological diseases in a
      population of pediatric organ transplant recipients, we studied a group of 217
      consecutive organ transplant recipients (168 kidney, 29 heart, 19 liver, one
      lung) aged <18 years at transplantation followed at a single center. A total of
      193 patients showed at least one skin disorder; 149 had more than one skin
      disease. The most common skin infections were warts (24.4%), pityriasis
      versicolor (20.7%), folliculitis (12.9%), intertrigo (6.5%); the most common drug
      side effects were hypertrichosis (69.6%), steroid acne (39.6%), gingival
      hyperplasia (29%) and severe xerosis (20.7%). Two patients (0.9%) developed
      nonmelanoma skin cancer. Our study summarizes the main skin complications in
      patients transplanted in childhood and underlines the necessity of regular
      dermatologic surveillance of these patients.

PMID- 15730500
TI  - Efficacy of rapamycin in patient with juvenile rheumatoid arthritis.
AB  - Juvenile rheumatoid arthritis (JRA) is an immune-mediated disease characterized
      by articular inflammation and subsequent tissue damage that may result in severe
      disability. Several combinations of drugs, including immunosuppressive agents
      have been used to control disease progression. Although there is no information
      available on rapamycin efficacy in JRA, it has demonstrated a potential to
      inhibit inflammatory processes observed in adult rheumatoid arthritis (RA). We
      present a 21 years old renal transplant recipient with JRA, primarily treated
      with tacrolimus and steroids, who achieved a long-term disease remission after
      introduction of rapamycin. As long as pathogenesis of JRA and RA is similar, we
      conclude that rapamycin could be promising immunosuppressant for patients after
      renal transplantation suffering from both JRA and RA.

PMID- 15730502
TI  - Editorial: north-south research collaborations: a move towards a true
      partnership?

PMID- 15730503
TI  - Assessing the health status of young AIDS and other orphans in Kampala, Uganda.
AB  - The huge number of human immunodeficiency virus (HIV)/acquired immunodeficiency
      syndrome (AIDS) orphans is an important feature of the epidemic in sub-Saharan
      Africa. There are few and conflicting data on the effects of being orphaned on
      health and nutrition in the highly affected HIV endemic areas of Africa. This
      study reports findings from a cross-sectional survey on associations between
      orphan status and health and nutrition parameters in young children of urban
      Uganda. A high prevalence of orphans was reported from a central Kampala
      community, with 41% being attributed to HIV/AIDS. Although there was a higher
      prevalence of self-reported morbidity in orphans than non-orphans, there were no
      differences in reported treatment seeking behaviour and measured anthropometric
      parameters. Hence it seems that the extended family system still manages to care
      for young orphans. Paying school fees for older children should be the primary
      target for HIV/AIDS impact mitigation programs in urban Uganda.

PMID- 15730504
TI  - Histoplasmine and paracoccidiodine epidemiological study in Upata, Bolivar state,
      Venezuela.
AB  - OBJECTIVE: To determine the prevalence of histoplasmosis and paracoccidiomycosis
      in Upata, a city in Bolivar state, Venezuela. METHODS: Cutaneous tests on 397
      volunteers, 204 with histoplasmine and 193 with paracoccidioidine.
      Epidemiological data were collected in a protocol sheet. Readings were performed
      at 24 and 48 h post-injection, by the same observer, and a positive reaction was
      defined as hardened papule of 5 mm or more. RESULTS: Histoplasmine tests were
      positive in 19.6% and 34.0% at 24 and 48 h after antigens injection with a
      significant increase of reactivity (P=0.0019). Paracoccidiodine tests were
      positive in 11.3% and 19.7% at 24 and 48 h respectively and this difference was
      also significant (P=0.004). Risk factors which could explain these levels of
      reactivity could not be clearly identified. Cultures and animal inoculation from
      soil samples for fungus isolation were negative. CONCLUSIONS:
      Paracoccidioidomycoses and histoplasmosis are endemic in Upata.

PMID- 15730505
TI  - Earth-eating and reinfection with intestinal helminths among pregnant and
      lactating women in western Kenya.
AB  - We conducted a longitudinal study among 827 pregnant women in Nyanza Province,
      western Kenya, to determine the effect of earth-eating on geohelminth reinfection
      after treatment. The women were recruited at a gestational age of 14-24 weeks
      (median: 17) and followed up to 6 months postpartum. The median age was 23
      (range: 14-47) years, the median parity 2 (range: 0-11). After deworming with
      mebendazole (500 mg, single dose) of those found infected at 32 weeks gestation,
      700 women were uninfected with Ascaris lumbricoides, 670 with Trichuris trichiura
      and 479 with hookworm. At delivery, 11.2%, 4.6% and 3.8% of these women were
      reinfected with hookworm, T. trichiura and A. lumbricoides respectively. The
      reinfection rate for hookworm was 14.8%, for T. trichiura 6.65, and for A.
      lumbricoides 5.2% at 3 months postpartum, and 16.0, 5.9 and 9.4% at 6 months
      postpartum. There was a significant difference in hookworm intensity at delivery
      between geophagous and non-geophagous women (P=0.03). Women who ate termite mound
      earth were more often and more intensely infected with hookworm at delivery than
      those eating other types of earth (P=0.07 and P=0.02 respectively). There were
      significant differences in the prevalence of A. lumbricoides between geophagous
      and non-geophagous women at 3 (P=0.001) and at 6 months postpartum (P=0.001).
      Women who ate termite mound earth had a higher prevalence of A. lumbricoides,
      compared with those eating other kinds of earth, at delivery (P=0.02), 3 months
      postpartum (P=0.001) and at 6 months postpartum (P=0.001). The intensity of
      infections with T. trichiura at 6 months postpartum was significantly different
      between geophagous and non-geophagous women (P=0.005). Our study shows that
      geophagy is associated with A. lumbricoides reinfection among pregnant and
      lactating women and that intensities built up more rapidly among geophagous
      women. Geophagy might be associated with reinfection with hookworm and T.
      trichiura, although these results were less unequivocal. These findings call for
      increased emphasis, in antenatal care, on the potential risks of earth-eating,
      and for deworming of women after delivery.

PMID- 15730506
TI  - Development and evaluation of an antigen detection dipstick assay for the
      diagnosis of human onchocerciasis.
AB  - To improve on the diagnosis of onchocerciasis, especially light infections, we
      developed and evaluated an oncho-dipstick test based on the detection of
      Onchocerca volvulus specific antigens in urine and tears. The test was able to
      detect as little as 25 ng/ml of parasite specific antigens in samples and took as
      little as 3 h. Evaluation of the assay on 456 residents of an onchocerciasis
      hyperendermic area in Cameroon resulted in 408 (89.5%) positives in urine and 374
      (82%) positives in tears. The prevalence of onchocerciasis in the study area, as
      determined by Rapid Epidemiological Mapping of Onchocerciasis (REMO) and skin
      snip methods, was 52 and 36.8%, respectively. The sensitivity of the oncho
      dipstick assay was 100% in urine and 92% in tears; its specificity was 100% in
      both. Concordance between urine and tear test results from the same individuals
      was 87%. The test strips were sufficiently reactive when left at room temperature
      for up to 8 months. The test would be useful for laboratory diagnosis of
      onchocerciasis in low transmission zones and to ascertain successful treatment of
      patients in experimental drug studies.

PMID- 15730507
TI  - High nasopharyngeal carriage of drug resistant Streptococcus pneumoniae and
      Haemophilus influenzae in North Indian schoolchildren.
AB  - OBJECTIVES: To determine the carriage rate of Streptococcus pneumoniae and
      Haemophilus influenzae in healthy Indian schoolchildren. The prevalence of
      antibiotic resistant strains in the community may be used to assess the trends of
      antibiotic resistance in invasive strains. Prevalence of resistance to various
      antimicrobial drugs among S. pneumoniae and H. influenzae was estimated. METHODS:
      Two thousand four hundred subjects, aged 5-10 years, were enrolled from 45 rural
      and 45 urban schools. A nasopharyngeal swab was collected from each child, after
      taking informed written consent. Swabs were processed to isolate S. pneumoniae
      and H. influenzae. All isolates were tested for resistance to chloramphenicol,
      erythromycin and co-trimoxazole. Streptococcus pneumoniae isolates were also
      tested against tetracycline and oxacillin while H. influenzae isolates were
      tested against ampicillin. RESULTS: Nasopharyngeal carriage of S. pneumoniae and
      H. influenzae was high in healthy schoolchildren. Stratified analysis showed that
      nasal carriage of pneumococci in urban children was significantly lower than in
      rural children [46.8% vs. 53.2%, P<0.001]. Carriage rates of H. influenzae in
      male and female populations were significantly different (47.8% vs. 52.3%,
      P<0.04). Penicillin resistance in S. pneumoniae was found low (3.3%), but 22.9%
      of H. influenzae isolates were ampicillin resistant. Resistance to co-trimoxazole
      was very high in both S. pneumoniae (81.8%) and H. influenzae (67.3%).
      CONCLUSION: There is high nasopharyngeal carriage of drug resistant S. pneumoniae
      and H. influenzae in schoolchildren of north India. Currently, in India, co
      trimoxazole for 5 days is recommended for treatment of non-severe pneumonia and
      third generation cephalosporins are drug of choice for management of severe
      pneumococcal/H. influenzae diseases. We found high co-trimoxazole resistance and
      low penicillin resistance in pneumococcal isolates. This justifies empirical use
      of penicillin in management of invasive pneumococcal infections in India.

PMID- 15730508
TI  - Determinants of health care seeking for childhood illnesses in Nairobi slums.
AB  - The practice of appropriate health seeking has a great potential to reduce the
      occurrence of severe and life-threatening child illnesses. We assessed the
      influence of socio-demographic, economic and disease-related factors in health
      care seeking for child illnesses among slum dwellers of Nairobi, Kenya. A survey
      round of the Nairobi Urban Demographic Surveillance System (NUDSS) generated
      information on 2-week child morbidity, illness symptoms, perceived illness
      severity and use of modern health services. During this round of data collection,
      interviewers visited a total of 15,174 households, where 3015 children younger
      than 5 years lived. Of the 999 (33.1%) children who were reported to have been
      sick, medical care of some sort was sought for 604 (60.5%). Lack of finances
      (49.6%) and a perception that the illness was not serious (28.1%) were the main
      reasons given for failure to seek health care outside the home. Health care
      seeking was most common for sick children in the youngest age group (0-11
      months). Caretakers sought medical care more frequently for diarrhoea symptoms
      than for coughing and even more so when the diarrhoea was associated with fever.
      Perception of illness severity was strongly associated with health care seeking.
      Household income was significantly associated with health care seeking up to
      certain threshold levels, above which its effects stabilized. Improving caretaker
      skills to recognize danger signs in child illnesses may enhance health-seeking
      behaviour. Integrated Management of Child Illnesses (IMCI) programmes must be
      accessible free of charge to the urban poor in order to increase health care
      seeking and bring about improvements in child survival.

PMID- 15730509
TI  - Collaboration between private pharmacies and national tuberculosis programme: an
      intervention in Bolivia.
AB  - BACKGROUND: Public-private partnerships are felt to be necessary for tuberculosis
      (TB) control in some developing countries. OBJECTIVES: To evaluate the potential
      of a collaboration between the National TB Programme (NTP) and private pharmacies
      in Bolivia, the country with the highest TB incidence in Latin America. METHODS:
      We contacted the local Pharmacists' Association in the city of Cochabamba, and
      designed a two phase intervention. The objectives of the first phase were to
      decrease the availability of TB drugs in private pharmacies on a voluntary basis,
      and to improve referral of clients seeking TB drugs to the NTP. A survey of all
      pharmacies allowed for a before-after comparison with a baseline survey. The
      objectives of the second phase were to obtain referral of pharmacy clients with
      chronic cough for TB screening in the NTP. This phase was started in 70
      pharmacies and evaluated after 2 months using the referral slips issued by the
      pharmacists. RESULTS: The proportion of pharmacies selling TB drugs decreased
      (rifampicin: 23-11.5%; isoniazid: 16-3.1%; P<0.001) and the proportion of
      pharmacies referring to the NTP clients seeking TB drugs increased (22-58%;
      P<0.0001). In the second phase, 26 of 70 pharmacies (38%) referred a total of 41
      clients for screening in the NTP (i.e. an average of 0.29 clients per pharmacy
      and per month); 11 of 41 (27%) were screened and three of 11 (27%) diagnosed with
      smear-positive TB. CONCLUSION: The first phase of the intervention proved
      effective in reducing the availability of the main TB drugs in pharmacies, and in
      improving referral of clients seeking TB drugs. Key factors in this success were
      not specific to Bolivia, and collaboration between private pharmacies and public
      services appears possible in that respect. However, collaboration with pharmacies
      does not seem an efficient way to increase the number of patients screened for
      TB, and to shorten delays to TB diagnosis and treatment.

PMID- 15730510
TI  - Behavioural heterogeneity of Anopheles species in ecologically different
      localities in Southeast Asia: a challenge for vector control.
AB  - In Southeast Asia the biodiversity of Anopheles species in the domestic
      environment is very high. Only few species are considered major vectors
      throughout the region, whereas the vector status of other species varies from
      area to area. Often it is difficult to identify an Anopheles species as a malaria
      vector in areas with low malaria incidence. The behaviour of Anopheles species
      largely determines their vector status, and insights into their behaviour are
      essential to evaluate the appropriateness of vector control measures. This study
      was conducted in six ecologically different localities in Southeast Asia to rank
      the different Anopheles species in terms of anthropophily and endophagy in order
      to estimate their current epidemiological importance. Concurrently, the biting
      and resting behaviour of the vectors was analysed to evaluate the appropriateness
      of insecticide-impregnated bed nets and residual house spraying in vector
      control. Anopheles dirus A was highly anthropophilic at all sites where it
      occurred. By contrast, the degree of anthropophily exhibited by An. minimus A
      depended on availability of cattle. Anopheles campestris, An. nimpe, An.
      sinensis, An. maculatus, An. aconitus showed a high degree of anthropophily in
      certain villages, indicating their potential of participating in malaria
      transmission, although the actual incidence of malaria in the study villages can
      be fully explained by transmission of the major vectors (An. dirus A, An. minimus
      A and An. sundaicus). Late biting of An. minimus A and biting activity throughout
      the night of An. sundaicus favour bed nets as a control method for these species,
      whilst exophilic and outdoor biting in combination with early feeding behaviour
      of An. dirus A will make both insecticide-impregnated bed nets and indoor
      residual spraying less suitable for controlling this species. Spatial variation
      in biting and resting behaviour was observed within almost all Anopheles species.
      These heterogeneities may result in the differences in epidemiological importance
      and in response to vector control of Anopheles species in different areas.
      Moreover, environmental changes and changes in human practice are expected to
      influence the behaviour, hence the role of the different species in malaria
      transmission. The effect of environmental changes on vector behaviour should be
      followed up carefully.

PMID- 15730511
TI  - A multi-group model of Schistosoma japonicum transmission dynamics and control:
      model calibration and control prediction.
AB  - Previously we formulated a quantitative model to characterize site-specific
      schistosomiasis transmission. In this paper, we present a procedure to calibrate
      the model to data collected in endemic villages of south-western Sichuan, China,
      with the objective of reducing parametric uncertainty to allow the model to
      describe local transmission with relative confidence. A Bayesian approach using
      local epidemiological data and expert opinion is employed to calibrate the model.
      Results indicate that, after calibration, the output uncertainty is reduced
      substantially. The calibrated model is then used for prediction of the effects of
      different intervention options. Simulations reflect a bimodal transmission in
      both human (early summer and early fall) and snail (late summer and late fall)
      infections in this area, for which there is some field evidence. Also shown in
      the simulations are relatively high reinfection rates following chemotherapy in
      these endemic villages. These results suggest that a sustainable control strategy
      is essential in reducing transmission, and that transmission can be reduced by
      chemotherapy, focal snail (e.g. snail clusters) control, and egg control. Our
      work demonstrates the feasibility of characterizing site-specific schistosomiasis
      transmission using a mathematical model and a calibration approach that
      integrates diverse field data, and the use of the calibrated model to design
      control strategies.

PMID- 15730512
TI  - A randomized comparative study of chloroquine, amodiaquine and sulphadoxine
      pyrimethamine for the treatment of uncomplicated malaria in Ghana.
AB  - The study examined the efficacy of chloroquine (CQ), amodiaquine (AQ) and
      sulphadoxine-pyrimethamine (SP) for the treatment of uncomplicated Plasmodium
      falciparum malaria in Ghana. A total of 351 children were randomized to receive
      either of the three study drugs. Patients were evaluated using the WHO 14-day in
      vivo antimalarial testing guidelines. The 14-day adequate clinical and
      parasitological response analysis revealed that CQ, 46.7% (95% CI 37.5, 56.0) has
      the least efficacy compared with AQ, 86.1% (95% CI 78.3, 91.8) and SP, 77.6% (95%
      CI 68.9, 84.8). Late parasite failures were also lower and similar in the AQ and
      SP (9.6% and 10.3%) than in the CQ (32.5%) group. However, CQ and AQ groups
      showed better fever clearance compared with SP throughout except for day 7 and
      after when possibly due to its significant late clinical failures, clearance by
      CQ was lower. Our findings suggest that CQ is no longer useful in Ghana and
      should be replaced as a first-line treatment of malaria. Replacement of CQ
      preferably with AQ combination treatment will be an effective and an affordable
      alternative for the treatment of uncomplicated malaria.

PMID- 15730513
TI  - Review Article: blood-brain barrier in falciparum malaria.
AB  - Plasmodium falciparum malaria is the most important parasitic disease infecting
      the central nervous system of humans worldwide. The pathogenesis of the
      neurological complications of falciparum malaria remains unclear. In particular,
      how do asexual parasites confined to the vascular space of the brain cause
      neuronal impairment? The evidence for a breakdown in the blood-brain barrier
      (BBB) is conflicting. In some animal models of malaria, there is evidence of
      breakdown of the BBB, but the data from humans suggests the BBB is mildly
      impaired only, with few morphological changes. Whether these changes in the BBB
      are sufficient to account for the neurological complications remains to be
      determined.

PMID- 15730514
TI  - Denaturing gradient gel electrophoresis and its use in the detection of major
      histocompatibility complex polymorphism.
AB  - The major histocompatibility complex (MHC) has been studied extensively in humans
      and in mice and many methods are available for MHC typing of these well
      characterized species. Studies of MHC variation in other species are ever
      increasing and researchers can choose one of a number of approaches for MHC
      typing of their species of interest. DNA sequencing is regarded as the 'gold
      standard' and it is frequently used for MHC typing. However, DNA sequencing is
      impractical when many individuals must be typed. Denaturing gradient gel
      electrophoresis (DGGE) offers a flexible and sensitive method for identifying and
      characterizing MHC alleles in any vertebrate species. This article reviews the
      theory and the practice of DGGE and examines the use of DGGE for MHC
      identification in various species. DGGE is compared to other similar techniques
      for MHC typing, such as single-stranded conformational polymorphism and reference
      strand-mediated conformational analysis. The advantages, problems, pitfalls and
      limitations of DGGE are considered and future perspectives on the use of DGGE for
      MHC typing are discussed.

PMID- 15730516
TI  - Development and characterization of rat monoclonal antibodies to denatured mouse
      angiotensin-converting enzyme.
AB  - Four new rat monoclonal antibodies, generated to denatured mouse somatic
      angiotensin-converting enzyme (ACE, CD143), detect mouse ACE with high
      sensitivity in Western blotting. Epitope mapping for the monoclonal antibodies-
      B12, 4G6 and 5C4--was also performed. Two monoclonal antibodies--B12 and 5C4--are
      directed to various epitopes on the N-domain--i.e., they recognized only the
      somatic isoform of mouse ACE. The monoclonal antibody H7 recognized an epitope on
      the C-domain of mouse ACE. The monoclonal antibody 4G6 was directed to a sequence
      on the N-domain of mouse ACE, which is homologous to a region of the C-domain
      and, as a result, also recognizes mouse testicular ACE (tACE) by means of Western
      blotting. In paraffin-embedded mouse tissues, all monoclonal antibodies detected
      all known expression sites of somatic ACE (sACE), e.g., the epithelial cells of
      the kidney proximal tubules, intestine and epididymis, and heterogeneously in
      endothelial cells. The monoclonal antibodies 4G6 and H7 additionally stained
      mouse tACE in spermatozoa and in mature spermatids. The monoclonal antibody 4G6
      also demonstrated cross-reactivity with sACE from a broad spectrum of animal
      species, including human, rat, rabbit and bovine. However, this monoclonal
      antibody did not recognize the testicular isoform of ACE of these species. This
      set of monoclonal antibodies is useful for identifying even subtle changes in
      mouse ACE conformation because of denaturation. These monoclonal antibodies are
      also sensitive tools for the detection of mouse ACE in biological fluids and
      tissues by using proteomics approaches. Their high reactivity in paraffin
      embedded tissues opens up opportunities to study possible changes in the pattern
      of ACE expression in knockout mouse models and may prove useful for correlating
      ACE expression in these models with human diseases.

PMID- 15730515
TI  - Epitope recognition of antibodies that define the sialomucin, endolyn (CD164), a
      negative regulator of haematopoiesis.
AB  - Endolyn (CD164) is a sialomucin that functions as an adhesion molecule and a
      negative regulator of CD34+ CD38- human haematopoietic precursor cell
      proliferation. The 105A5 and 103B2/9E10 CD164 monoclonal antibodies (mAbs), which
      act as surrogate ligands, recognize distinct glycosylation-dependent classes I
      and II epitopes located on domain I of the native and recombinant CD164 proteins.
      Here, we document five new CD164 mAbs, the 96 series, that rely on conformational
      integrity, but not glycosylation, of exons 2- and 3-encoded CD164 domains,
      thereby resembling the class III mAbs, N6B6 and 67D2. Although all the 96 series
      class III mAbs labelled both the 105A5+ and 103B2/9E10+ cells, cross-competition
      and immunoblotting studies allow them to be categorized into two distinct class
      III subgroups, i.e. the N6B6-like subgroup that only recognizes 80-100 kDa
      proteins and the 67D2-like subgroup that also recognizes a higher molecular
      weight (>220 kDa) form. To more closely define the reactivity patterns of mAbs to
      the classes I and II epitopes, the global glycosylation patterns of the soluble
      human (h) CD164 proteins were determined using lectin binding, high-performance
      liquid chromatography (HPLC) and mass spectrometry. hCD164 recombinant proteins
      bound to the lectins, Galanthus nivalis agglutinin, Datura stramonium agglutinin,
      Sambucus nigra agglutinin, Maackia amurensis agglutinin and peanut agglutinin,
      indicating the presence of high mannose and complex N-glycans, in addition to
      core 1 O-glycans (the Tn antigen) and alpha2-3 and alpha2-6 sialic acid moieties.
      Our HPLC and mass spectrometry results revealed both high mannose and complex N
      glycosylation with various numbers of branches increasing the complexity of the
      glycosylation pattern. Most O-glycans were small, core 1 or 2 based. High levels
      of sialylation in alpha2-3 and alpha2-6 linkages, without sialyl-Lewis X,
      indicate that the majority of these hCD164 recombinant proteins are unable to
      bind to selectins in our assay system, but may interact with Siglec molecules.

PMID- 15730517
TI  - A population-based cohort study of KIR genes and genotypes in relation to
      cervical intraepithelial neoplasia.
AB  - Natural killer (NK) cells are involved both in control of virus infections and in
      elimination of tumor cells. Killer immunoglobulin-like receptors (KIRs) either
      activate or inhibit NK cell-mediated cytolysis, protecting healthy cells from
      destruction while enabling killing of abnormal cells. To investigate whether KIR
      genes or genotypes are associated with cervical carcinogenesis, a nested case
      control study of 65 case women with cervical intraepithelial neoplasia (CIN)
      diagnosed during a 6-year follow-up of 15,234 women and 150 control women from
      the same cohort that remained healthy was performed. More than 70 different
      genotypes were observed, and 33 of which had not been described previously. An A
      genotype including KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, KIR3DL3,
      and KIR2DS4 was associated with increased risk of CIN (OR 6.7; 95% CI 1.7-26.3),
      and KIR2DL5B*002 appeared to have an inverse association with disease (OR 0.5;
      95% CI 0.5-2.9). There was no association of CIN with the number of activating
      KIR genes. There was also no association between KIR genes and type of human
      papilloma virus or with other CIN-related immune response genes. It was concluded
      that certain KIR genes and genotypes may associate with cervical neoplasia.

PMID- 15730518
TI  - Association of HYPA haplotype in the mannose-binding lectin gene-2 with Behcet's
      disease.
AB  - Behcet's disease (BD) is a multisystemic, recurrent inflammatory disease caused
      by the combinations of multiple genetic and environmental factors. Moreover, the
      MBL2 gene single-nucleotide polymorphisms and haplotypes are known to increase
      the susceptibility to inflammatory disease and to alter the serum levels of
      mannose-binding lectin (MBL. We postulated that the haplotypes of the MBL2 gene
      influence therapeutic response in BD, thus affecting the clinical symptoms in 282
      BD patients. The promoter region, MBL2-550*C/*C (L/L) homozygote was found to
      have a lower frequency in BD patients than that in controls. No difference was
      observed in the allele frequencies of G-221C (Y/X), C+4T (P/Q) or Gly54Asp (A/B)
      of the MBL2 gene in BD patients and in controls. The HYPA haplotype contributed
      to BD occurrence, whereas the LYPA haplotype was negatively associated with BD.
      BD patients with several symptoms and with an earlier disease-onset age had a
      higher HYPA haplotype frequency. BD patients showing poor response (S) to therapy
      had a higher HYPA frequency than those showing good response (M). It seems that
      possessing HYPA increases the risk of BD and that the MBL2 HYPA haplotype plays a
      role in MBL levels and increases the susceptibility to BD.

PMID- 15730519
TI  - Association study of Toll-like receptor 9 gene polymorphism in Korean patients
      with systemic lupus erythematosus.
AB  - Mammalian Toll-like receptors (TLR) play an important role in both adaptive
      immunity and innate immunity. Genetic variations within TLR genes are known to be
      associated with a variety of inflammatory and infectious diseases. TLR9 is
      potentially associated with autoimmune diseases, because it participates in the
      production of pro-inflammatory cytokines and the maturation of dendritic cells.
      We investigated the association of four TLR9 gene polymorphisms (-1486 T>C, -1237
      C>T, +1174 A>G and +2848 G>A) with the susceptibility to systemic lupus
      erythematosus (SLE) and related phenotypes in 680 Korean people (350 SLE patients
      and 330 controls). TLR9 gene polymorphisms were not significantly associated with
      the susceptibility to SLE and related phenotypes.

PMID- 15730520
TI  - Haplotype analysis of the CD11 gene cluster in patients with chronic Helicobacter
      pylori infection and gastric ulcer disease.
AB  - Helicobacter pylori infection leads to a broad spectrum of disease manifestations
      such as gastritis, ulcer disease, and even gastric carcinoma. The genetically
      determined immune response and subsequent inflammation influence the degree of
      mucosal damage. Adhesion molecules of the CD11 cluster play an important role in
      adherence of neutrophils to endothelial cells in inflammation. We conducted a
      haplotype-based analysis of the CD11 cluster in a sample of 315 patients with H.
      pylori infection and investigated associations with gastric erosions and ulcer
      disease. Twelve single nucleotide polymorphisms (SNPs) covering the genes CD11a,
      CD11b, and CD11c were genotyped by Taqman technology. Linkage disequilibrium (LD)
      was assessed within the CD11 cluster and haplotype case-control analysis was
      conducted. Sliding window haplotype analysis identified a haplotype consisting of
      the markers CD11c exon 15 and intron 31 associated with gastric ulcer disease.
      Patients carrying the haplotype GA bear a 2.4-fold increased risk. No significant
      associations of single markers with disease outcome were found. High-density LD
      mapping and mutation detection of CD11c in larger samples will be necessary to
      confirm our findings and identify the causative variant. Thus, we conclude that
      genetic variants in the CD11 cluster may play a role in the development of
      gastric ulcer in chronic H. pylori infection presumably by influencing leukocyte
      adhesion. The biological effect of genetic variants of CD11c in gastric
      inflammation needs further clarification.

PMID- 15730522
TI  - Identification of a new HLA-B*56 variant, B*5614.
AB  - In this report, the novel allele B*5614 is presented. The allele was identified
      in a Chinese individual by sequence-based typing. HLA-B*5614 differs from B*5608
      by a single nucleotide at position 277G-->C in exon 2. This results in an amino
      acid change from Gly to Arg at codon 93.

PMID- 15730521
TI  - A novel HLA-B*420502 allele identified by PCR-SSO/SSP routine typing and
      confirmed by Sequencing-based typing.
AB  - A novel human leukocyte antigen-B (HLA-B) allele, B*420502, was identified in a
      patient with leukemia (Caucasoid, Czech ancestry) and his mother during
      intrafamily search for the hematopoietic stem cell donor. The novel allele was
      initially detected by HLA typing at low resolution using both sequence specific
      primers and sequence specific oligonucleotides techniques that resulted in unique
      reaction patterns. The alleles of the HLA-B locus were separated by the haplotype
      specific extraction technique. Sequencing of those alleles revealed a novel
      allele, B*420502, that is identical with B*420501 except a T-->G exchange
      (synonymous mutation) at position 618.

PMID- 15730523
TI  - Identification of HLA-B*5136 in the Chinese population.
AB  - We report here a new HLA-B*5136 allele identified by sequence-based typing in the
      Chinese population. The new B*5136 allele showed four nucleotides difference with
      B*5108 at exon 3, which are two point mutations at nucleotide positions 527 T-->A
      and 583 C-->T, and two substitutions at adjacent nucleotide positions 559 C-->A
      and 560 T-->C. This results in three amino acid changes from Val to Glu at codon
      177, Leu to Thr at codon 187, and His to Tyr at codon 195.

PMID- 15730524
TI  - Conservation of MHC class II DOA sequences among carnivores.
AB  - We obtained the nucleotide sequence for most of the major histocompatibility
      complex (MHC) class II DOA locus for Weddell, leopard, northern elephant, and
      southern elephant seals and from the coyote and compared them to all known DOA
      data available to date. We found generally low levels of interspecific
      polymorphisms, providing further support for stabilizing selection acting on the
      DOA locus. This suggests that DO gene products play a substantial functional role
      in the regulation of antigen presentation. A seven-amino-acid motif of VWRLPEF
      was found to be conserved across all DOA sequences and may be a DO-specific
      recognition element.

PMID- 15730525
TI  - Identification of a novel HLA-DOB-allele, DOB*010103, by sequence-based typing in
      the Korean population.
AB  - A new DOB allele, DOB*010103, was identified in the Korean population during
      sequence-based HLA-DOB typing. DOB*010103 differed from DOB*01010101 only at
      codon 6 (GAT-->GAC), corresponding to synonymous amino acid change (Asp-->Asp).

PMID- 15730526
TI  - HLA-DPB1 allelic frequency of the Lisu ethnic group in the Southwest China and
      evolutionary relationship of Lisu with other populations.
AB  - A sequencing-based typing of human leukocyte antigen-DPB1 (HLA-DPB1) gene was
      carried out in 37 unrelated healthy individuals from the Yunnan Lisu ethnic
      minority. A total of 12 DPB1 alleles, in which DPB1*1301 (33.3%), DPB1*0402
      (16.6%), DPB1*040101 (13.8%), and DPB1*0501 (11.1%) were highly predominant, were
      found, and allele DPB1*200102 was found for the first time in a Chinese
      population. A dendrogram constructed by neighbor-joining method showed that the
      Lisu ethnic group belongs to East Asian cluster.

PMID- 15730527
TI  - A novel HLA-DRB1*09 allele, HLA-DRB1*090103*, isolated from the Han population of
      Guangdong, China.
AB  - A novel HLA-DRB1*09 allele, HLA-DRB1*090103, has been identified in a Guangdong
      Han person. Its sequence was confirmed by sequencing polymerase chain reaction
      products and clones. This allele differed by one nucleotide from HLA-DRB1*090102
      at position 50(G-->C), which represents a silent mutation.

PMID- 15730528
TI  - HPA polymorphism in sub-Saharan African populations: Beninese, Cameroonians,
      Congolese, and Pygmies.
AB  - The frequency of human platelet antigen-1 (HPA-1) to HPA-11w (excluding HPA-8w)
      and HPA-15 systems was studied in four sub-Saharan populations: Beninese,
      Congolese (Democratic Republic of Congo Kinshasa), Cameroonians, and Aka pygmies
      (Central African Republic). No report of HPA prevalence has previously been
      published concerning these populations which are characterized by the highest HPA
      2b gene frequencies of any reported to date (Aka 0.393, Benin 0.292, Cameroon
      0.237, and Congo 0.224) and at lesser degree HPA-5b (Aka 0.405, Congo 0.268,
      Cameroon 0.254, and Benin 0.182). This study is of great importance (i)
      particularly in the context of the diversity caused by the population migrations,
      we may observe today in our hospitals (ii) to confirm that the Pygmy population
      with distinctive frequencies (absence of the HPA-1b, HPA-2b, and HPA-5b highest
      frequencies) is an isolated population.

PMID- 15730529
TI  - Nomenclature for factors of the HLA system, update December 2004.

PMID- 15730530
TI  - Proteomic identification of the involvement of the mitochondrial rieske protein
      in epilepsy.
AB  - PURPOSE: Kindled seizures are widely used to model epileptogenesis, but the
      molecular mechanisms underlying the attainment of kindling status are largely
      unknown. Recently we showed that achievement of kindling status in the Sprague
      Dawley rat is associated with a critical developmental interval of 25 +/- 1 days;
      the identification of this long, well-defined developmental interval for inducing
      kindling status makes possible a dissection of the cellular and genetic events
      underlying this phenomenon and its relation to normal and pathologic brain
      function. METHODS: By using proteomics on cerebral tissue from our new rat
      kindling model, we undertook a global analysis of protein expression in kindled
      animals. Some of the identified proteins were further investigated by using
      immunohistochemistry. RESULTS: We report the identification of a modified variant
      of the Rieske iron-sulfur protein, a component of the mitochondrial cytochrome
      bc1 complex, whose isoelectric point is shifted toward more alkaline values in
      the hippocampus of kindled rats. By immunohistochemistry, the Rieske protein is
      well expressed in the hippocampus, except in the CA1 subfield, an area of
      selective vulnerability to seizures in humans and animal models. We also noted an
      asymmetric, selective expression of the Rieske protein in the subgranular neurons
      of the dorsal dentate gyrus, a region implicated in neurogenesis. CONCLUSIONS:
      These results indicate that the Rieske protein may play a role in the response of
      neurons to seizure activity and could give important new insights into the
      molecular pathogenesis of epilepsy.

PMID- 15730531
TI  - Pharmacodynamic and pharmacokinetic interaction studies of loreclezole with
      felbamate, lamotrigine, topiramate, and oxcarbazepine in the mouse maximal
      electroshock seizure model.
AB  - PURPOSE: The study investigated the types of interactions between loreclezole
      (LCZ) and a variety of newly licensed antiepileptic drugs (AEDs) with different
      mechanisms of actions [felbamate (FBM), lamotrigine (LTG), topiramate (TPM), and
      oxcarbazepine (OXC)] by isobolographic analysis. METHODS: Anticonvulsant and
      adverse-effect profiles of combinations of LCZ with other AEDs at fixed ratios of
      1:3, 1:1, and 3:1 were investigated in the maximal electroshock (MES)-induced
      seizures and the chimney test (as a measure of motor impairment) in mice so as to
      identify optimal combinations. Protective indices (PIs) and benefit indices (BIs)
      were calculated so that a ranking in relation to advantageous combinations could
      be established. RESULTS: With isobolography, it was observed that the combination
      of LCZ and TPM, at the fixed ratios of 1:1 and 3:1, was supraadditive
      (synergistic; p < 0.05), whereas LCZ with TPM at the fixed ratio of 1:3 and LCZ
      combined with LTG, FBM, or OXC at the fixed ratios of 1:3, 1:1, and 3:1 were
      associated with additive interactions. Moreover, the isobolographic analysis in
      the chimney test revealed that only one combination tested (LCZ and TPM at the
      fixed ratio of 1:1) was subadditive (antagonistic; p < 0.05), whereas the
      remaining combinations of LCZ with LTG, FBM, or OXC (at the fixed ratios of 1:3,
      1:1, and 3:1) barely displayed additivity. However, these combinations were
      associated with significant pharmacokinetic interactions, in that LCZ increased
      brain TPM (94%), OXC (21%), FBM (46%), and LTG (8%) concentrations. In addition,
      brain LCZ concentrations were decreased by TPM (26%), OXC (37%), LTG (42%), and
      FBM (19%). None of the examined combinations between LCZ and TPM, OXC, LTG, and
      FBM altered long-term memory in the step-through passive-avoidance task.
      CONCLUSIONS: LCZ plus TPM appears to be a particularly favorable combination,
      based on the MES test and the chimney test. LCZ and OXC also is a favorable
      combination. However, these conclusions are confounded by the fact that LCZ is
      associated with significant pharmacokinetic interactions.

PMID- 15730532
TI  - Increased seizure susceptibility of the hippocampus compared with the neocortex
      of the immature mouse brain in vitro.
AB  - PURPOSE: The temporal lobe seems particularly susceptible to seizure activity.
      Mesial temporal lobe structures, including the hippocampus, have the lowest
      seizure thresholds in the brain. Conversely, thresholds in the frontal neocortex
      are significantly higher. The development of intact, isolated preparations of
      hippocampus and neocortex in vitro allows for study into mechanisms governing
      seizure threshold. METHODS: Epileptiform discharges in isolated mouse neocortical
      blocks were compared with the contralateral intact hippocampus, isolated from the
      same brain, by using the low-Mg2+, 4 aminopyridine (4-AP), and low-Ca2+ in vitro
      seizure models. The pharmacology of low Mg(2+)-induced ictal-like events (ILEs)
      generated in the hippocampus and neocortex was then compared by using
      glutamatergic antagonists DL-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7
      nitro-quinoxaline-2,3-dione (CNQX), and the Ca2+ channel antagonist, nifedipine.
      RESULTS: Neocortical blocks generated both recurrent, spontaneous ILEs and
      interictal-like events under low-Mg2+ artificial CSF (aCSF) perfusion, distinct
      from those generated in the hippocampus. ILEs from the hippocampus displayed
      lower thresholds and longer durations as compared with isolated neocortical
      blocks. Similar results were obtained during 4-AP perfusion. Perfusion with low
      Ca2+ ACSF did not produce stereotypical ILEs in the neocortical block, producing
      instead recurrent, slow depolarizations. Both ILEs and recurrent, slow
      depolarizations were produced in the hippocampus. Application of APV and
      nifedipine exacerbated low Mg(2+)-induced ILEs in the hippocampus but not the
      neocortex, indicating a distinct pharmacology for partial seizures of different
      brain regions. CONCLUSIONS: The developing mouse hippocampus demonstrates
      increased ictogenesis compared with the developing neocortex in vitro, consistent
      with clinical observations and in vivo experimental models.

PMID- 15730533
TI  - Changes in baroreflex responses of kindled rats.
AB  - PURPOSE: This study was planned to investigate the baroreflex responses (BRs) in
      kindled rats during seizure-free period to put forward new data on cardiac
      autonomic changes in epilepsy. METHODS: Male Wistar rats were randomized into
      sham-operated (SO) and kindled groups where stimulation and recording electrodes
      were implanted stereotaxically into the basolateral amygdala and the cortex,
      respectively. For kindling process, rats were stimulated twice daily at their
      afterdischarge threshold current and accepted as being kindled after 10 grade 5
      seizures. Six to 8 weeks after the establishment of the kindled state, mean
      arterial pressure (MAP) and heart rate (HR) were evaluated. BR was defined as the
      ratio of HR response to changes in MAP induced by i.v. nitroprusside (10, 25
      microg/kg) or i.v. phenylephrine (10, 25 microg/kg). The sympathetic or
      parasympathetic component of the BR was evaluated in rats pretreated with
      atropine or atenolol where phenylephrine or nitroprusside was administered at 25
      microg/kg. RESULTS: Basal MAP and HR values were found to be similar in SO and
      kindled rats. Phenylephrine increased MAP more in the kindled group (p < 0.05),
      but the HR decreased similarly in both groups. Nitroprusside decreased MAP at
      similar rates, but the increase in HR was higher in the kindled rats (p < 0.05).
      BRs to phenylephrine and nitroprusside were abolished after pretreatment with
      atenolol and atropine, whereas phenylephrine- and nitroprusside-induced changes
      in MAP remained unchanged in both groups. CONCLUSIONS: These results may indicate
      that amygdaloid kindling affects BRs in long-term seizure-free periods.

PMID- 15730534
TI  - Phenobarbital pharmacokinetics in old age: a case-matched evaluation based on
      therapeutic drug monitoring data.
AB  - PURPOSE: To assess the influence of aging on the pharmacokinetics of
      phenobarbital (PB) at steady state in patients receiving long-term therapy.
      METHODS: Serum PB concentrations from the database of the therapeutic drug
      monitoring service of a large neurological hospital were used to calculate
      apparent clearance values (CL/F) in 224 patients aged 65 years and older (mean,
      73 +/- 6.1 years). CL/F values in these patients were compared with those
      determined in an equal number of controls aged 20 to 50 years (mean, 35.7 +/- 7.9
      years) and matched for gender, body weight, and type of anticonvulsant
      comedication. Correlations of CL/F with age, body weight, gender, and
      comedication also were explored within each age group. RESULTS: PB CL/F values
      were significantly lower in elderly patients than in controls (3.2 +/- 0.8 vs.
      4.1 +/- 1.2 ml/h/kg; p < 0.0001). Age was identified as a statistically
      significant predictor of CL/F at multiple regression analysis, but it accounted
      for only a modest component of the interindividual pharmacokinetic variation.
      Comedication with carbamazepine (CBZ) and phenytoin (PHT) was associated with a
      moderate decrease in PB CL/F, which reached statistical significance in the
      elderly group (p < 0.01 for CBZ comedication; p < 0.001 for PHT comedication).
      CONCLUSIONS: Aging is associated with a significant decrease in PB clearance,
      which might be related to a reduction in glomerular filtration rate or diminished
      drug-metabolizing capacity in the liver or both. Because of this, older patients
      will require lower dosages to achieve serum PB concentrations comparable with
      those found in nonelderly adults.

PMID- 15730535
TI  - Pharmacokinetic and metabolic investigation of topiramate disposition in healthy
      subjects in the absence and in the presence of enzyme induction by carbamazepine.
AB  - PURPOSE: To characterize the metabolic profile of topiramate (TPM) in humans and
      to assess the influence of enzyme induction by carbamazepine (CBZ) on the
      pharmacokinetics and metabolic profile of TPM. METHODS: Twelve healthy subjects
      received a single oral dose of TPM (200 mg) on two randomized occasions. On one
      occasion, TPM was administered alone, and on the other, it was given on day 18 of
      a 24-day treatment with CBZ (maintenance dosage, 600 mg/day). Blood and urine
      samples were collected for > or = 72 h after dosing. TPM and its metabolites were
      assayed in plasma and urine by a specific liquid chromatography-mass spectroscopy
      (LC-MS) method. RESULTS: Mean TPM oral clearance (CL/F) increased from 1.2 L/h
      (control) to 2.2 L/h after CBZ treatment. Mean TPM half-life decreased from 29 h
      to 19 h. TPM was excreted extensively in urine both under noninduced (56%) and
      CBZ-induced conditions (40%). 2,3-O-Des-isopropylidene-TPM (2,3-diol-TPM) was
      identified as the most prominent urinary metabolite, with a recovery accounting
      for 3.2% and 7.9% of the TPM dose under noninduced and induced conditions,
      respectively. Corresponding recovery values for 10-hydroxy-TPM (10-OH-TPM) were
      1.2% and 1.8%, respectively. The control AUC(metabolite)/AUC(drug) ratio for 2,3
      diol-TPM and 10-OH-TPM were 1.5% and 0.6%, and they increased by threefold and
      twofold, respectively, after CBZ treatment. CONCLUSIONS: TPM remains appreciably
      excreted unchanged in urine (41%) under CBZ-induced conditions, even though TPM
      CL/F increased by twofold. Although 2,3-diol-TPM and 10-OH-TPM were measured in
      unconjugated form, the significant increases in their AUC and urinary excretion
      are consistent with the twofold increase in TPM clearance.

PMID- 15730536
TI  - Seizure anticipation: do mathematical measures correlate with video-EEG
      evaluation?
AB  - PURPOSE: Analysis of the EEG signal has recently shown evidence of dynamic
      changes preceding ictal onset in seizures selected from patients with clear
      epileptogenic foci. Most of the studies were conducted in highly selected EEG
      epochs and patients. In addition, these studies relied mostly on mathematical
      approaches and neglected clinical and visual EEG parameters. We therefore
      performed a systematic comparison of a nonlinear method (the similarity measure)
      with classic visual inspection of the EEG and the patient's clinical state.
      METHODS: We analyzed the dynamics of long epochs of intracranial EEG containing
      129 electroclinical and 45 electrographic seizures in 13 successive unselected
      patients undergoing presurgical evaluation. RESULTS: (a) The similarity measure
      detected preictal dynamical changes of the EEG signal in two thirds of the
      seizures whether or not a clear focus was identified, and whether seizures were
      electroclinical or purely electrographic. The mean duration of preictal changes
      was 12 min. (b) The preictal changes were correlated with various visually
      detectable EEG changes in 78.9% of electroclinical seizures. (c) 81.5% of the
      preictal dynamic changes were correlated with changes of vigilance or behavior.
      (d) Fluctuations of the dynamics were not necessarily followed by seizures.
      CONCLUSIONS: Our results indicate that EEG dynamics frequently change before
      seizures. These preictal changes are most often associated with the EEG changes
      accompanying transitions between states of vigilance. The preictal dynamic
      changes may represent physiologic changes acting as facilitating factors or
      pathologic changes reflecting a network dysfunction.

PMID- 15730537
TI  - Dipole modeling of epileptic spikes can be accurate or misleading.
AB  - PURPOSE: We investigated the accuracy and potential for serious error when
      representing cortical generators of epileptic spikes with the common single
      dipole model. Spike generators were realistically simulated with cortical areas
      of different extents. METHODS: The source was simulated by using a patch that
      comprised small triangles on the cortical surface, each triangle having an
      elementary dipole generator with a moment corresponding to real intracerebral
      fields of spikes. The source-patch covered various clinically important parts of
      the temporal and frontal lobes, with an area ranging from 6 to 120 cm2. The scalp
      field was computed for each source-patch by using a realistic head model and was
      fitted by the single-dipole model to determine the best-fit dipole and the
      intracerebral distribution of residual variance (RV). Dipole modeling also was
      performed for the simulated scalp field with additional real EEG background.
      RESULTS: The RV after fitting a dipole to the scalp field without noise was at
      most 1.34%. Scalp spikes arising from sources of 6 cm2 were of small amplitude,
      and the dipoles estimated for these spikes were inconsistent. Extension of the
      source area was associated with increase of scalp potential amplitude, only very
      small increase of RV, and increased consistency of the estimated dipoles. When
      the source was very large, the dipoles clustered at very misleading locations.
      CONCLUSIONS: Pitfalls in dipole source localization are caused by the procedure
      of fitting the simplistic dipole model to real cortical sources with spatial
      extent and complex configuration.

PMID- 15730538
TI  - Removing eye-movement artifacts from the EEG during the intracarotid amobarbital
      procedure.
AB  - PURPOSE: The EEG is often recorded during the intracarotid amobarbital procedure
      (IAP) to help in the assessment of the spatial extent and the duration of the
      effect of the drug. In scalp recordings, the EEG is always heavily contaminated
      with eye movement artifacts as the patient actively performs visual tasks.
      METHODS: Independent component analysis (ICA) is a new technique for blind source
      separation. In this study, we separated the EEG data recorded during the IAP into
      independent components using ICA. The EEG signal was reconstructed by excluding
      the components related to eye movement and eye blinks. RESULTS: EEGs from 10 IAP
      tests were analyzed. The experimental results indicate that ICA is very efficient
      at subtracting eye-movement artifacts, while retaining the EEG slow waves and
      making their interpretation easier. CONCLUSIONS: ICA appears to be a generally
      applicable and effective method for removing ocular artifacts from EEG recordings
      during IAP, although slow waves and ocular artifacts share similar frequency
      distributions.

PMID- 15730539
TI  - Consistent localization of interictal epileptiform activity on EEGs of patients
      with tuberous sclerosis complex.
AB  - PURPOSE: We addressed consistent localization of focal interictal epileptiform
      activity on EEGs of patients with tuberous sclerosis complex (TSC) and epilepsy.
      METHODS: Twenty-one patients with TSC with a 10-year history of epilepsy and
      interictal epileptiform activity in three or more EEG recordings were included.
      None of the patients had undergone epilepsy surgery. Local maxima of interictal
      epileptiform activity were measured from 76 EEG traces and 33 EEG reports.
      Information about the patients' clinical course was extracted from their medical
      records. Magnetic resonance imaging (MRI) and neuropsychological examinations
      were performed. Statistical analysis was performed with the Mann-Whitney U test.
      RESULTS: In eight patients, interictal epileptiform activity was consistently
      detected in one or two regions (group 1), and in 13 patients, epileptiform
      activity was detected in three or more regions (group 2). The number of foci
      increased throughout the disease course in both groups. Age at seizure onset and
      IQ were significantly higher in group 1. Complex partial seizures occurred more
      often in the patients of group 1. In 19 of the 21 patients, the most consistent
      epileptiform activity was localized in the frontotemporal region. CONCLUSIONS:
      Ninety percent of patients with TSC showed at least one region of consistent
      interictal epileptiform activity. Patients with one or two regions of
      epileptiform activity were older at seizure onset, often experienced complex
      partial seizures, and had mild or no mental deficits. These patients may be
      candidates for epilepsy surgery.

PMID- 15730540
TI  - Ipsilateral and contralateral MRI volumetric abnormalities in chronic unilateral
      temporal lobe epilepsy and their clinical correlates.
AB  - PURPOSE: To assess the presence, extent, and clinical correlates of quantitative
      MR volumetric abnormalities in ipsilateral and contralateral hippocampus, and
      temporal and extratemporal lobe regions in unilateral temporal lobe epilepsy
      (TLE). METHODS: In total, 34 subjects with unilateral left (n = 15) or right (n =
      19) TLE were compared with 65 healthy controls. Regions of interest included the
      ipsilateral and contralateral hippocampus as well as temporal, frontal, parietal,
      and occipital lobe gray and white matter. Clinical markers of neurodevelopmental
      insult (initial precipitating insult, early age of recurrent seizures) and
      chronicity of epilepsy (epilepsy duration, estimated number of lifetime
      generalized seizures) were related to magnetic resonance (MR) volume
      abnormalities. RESULTS: Quantitative MR abnormalities extend beyond the
      ipsilateral hippocampus and temporal lobe with extratemporal (frontal and
      parietal lobe) reductions in cerebral white matter, especially ipsilateral but
      also contralateral to the side of seizure onset. Volumetric abnormalities in
      ipsilateral hippocampus and bilateral cerebral white matter are associated with
      factors related to both the onset and the chronicity of the patients' epilepsy.
      CONCLUSIONS: These cross-sectional findings support the view that volumetric
      abnormalities in chronic TLE are associated with a combination of
      neurodevelopmental and progressive effects, characterized by a prominent
      disruption in ipsilateral hippocampus and neural connectivity (i.e., white matter
      volume loss) that extends beyond the temporal lobe, affecting both ipsilateral
      and contralateral hemispheres.

PMID- 15730541
TI  - The effects on cognitive performance of tailored resection in surgery for
      nonlesional mesiotemporal lobe epilepsy.
AB  - PURPOSE: Mesiotemporal lobe epilepsy (MTLE) can be treated with different
      surgical approaches. In tailored resections, neocortex is removed beyond
      "standard" margins when spikes are present in the electrocorticogram. We
      hypothesized that these larger resections are justified because spiking neocortex
      is dysfunctional. This would imply that in patients with spikes (a) postoperative
      cognitive performance is not affected, and (b) preoperative performance is worse
      than without spikes. METHODS: We studied 80 operated-on MTLE patients with
      pathologically confirmed nonlesional hippocampal sclerosis. All patients were
      left-sided language dominant and underwent cognitive tests 6 months pre- and
      postoperatively. A repeated measures analysis of variance (ANOVA) was performed,
      looking for within- and between-subjects interactions with presence of
      intraoperative neocortical spikes. RESULTS: Intraoperatively, neocortical spikes
      were present in 61% of patients. Improved postoperative cognitive outcome was
      seen only in left-sided patients with spikes. Their performance IQ (PIQ)
      increased by 8.1 points (95% confidence interval, 3.8-12.3; p = 0.02), and visual
      naming latency by 12.8 s (95% CI, 2.1-23.5; p = 0.07). Conversely, in left-sided
      patients without spikes, naming latency declined by 7.5 s (95% CI, -2.3-17.2; p =
      0.07). Preoperative scores were comparable except for a 15.3-point (95% CI, 0.1
      30.5; p = 0.02) lower VIQ in left-sided patients without spikes. CONCLUSIONS:
      Tailoring does not harm cognitive performance and is, in left-sided MTLE,
      associated with postoperative improvement. Left-sided MTLE without neocortical
      spikes has lower verbal scores, which tend to decline after standard resection
      and may represent a special pathophysiologic entity.

PMID- 15730542
TI  - Extended-release divalproex in child and adolescent outpatients with epilepsy.
AB  - PURPOSE: To determine whether valproic acid [divalproex (DVP)] extended-release,
      administered at a higher proportionate once-daily dosage, can be safely
      substituted for delayed-release or sprinkle in pediatric patients with epilepsy.
      METHODS: Patients between ages 6 and 17 years with stable epilepsy taking DVP
      were randomized to 7 days of either DVP delayed-release/sprinkle (at the usual
      daily dose taken before study entry) or extended-release DVP (daily dose, 8% to
      25% higher than their usual dose), and then (crossed over to) 7 days of the
      comparator formulation. Patient's clinical status was evaluated at a screening
      visit and on days 8 and 15, and with telephone follow-up 1 month after study
      completion. RESULTS: No statistically significant difference in mean plasma VPA
      levels measured at the end of treatment was observed: 99, 92, and 103 mug/ml with
      the delayed-release tablets (n = 4), the sprinkle formulation (n = 11), and the
      extended-release tablets (n = 16), respectively. Seizure-control rates were
      stable during patients' use of the extended-release formulation. None of the
      study patients experienced a treatment-related adverse event. CONCLUSIONS: The
      total daily dose for patients taking the delayed-formulation may need to be
      increased by < or = 20% when they are switched to the extended-release
      formulation. When switching from sprinkles to the extended-release formulation,
      individual variability must be considered. In patients who have VPA levels near
      the very high end of the therapeutic range (>100 microg/ml), it may be more
      prudent to make only minor modifications to the total daily dose during
      conversion and then to individualize the DVP extended-release dose based on
      plasma levels.

PMID- 15730543
TI  - Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and
      3beta-hydroxysteroid dehydrogenase type 2.
AB  - PURPOSE: Women with epilepsy apparently have a higher incidence of polycystic
      ovary syndrome (PCOS) than do women without epilepsy. Whether the underlying
      disease or the antiepileptic drug (AED) treatment is responsible for this
      increased risk is unknown, although clinical reports implicate valproic acid
      (VPA) as a potential cause. The steroidogenic enzymes 3beta HSDII (3beta
      hydroxysteroid dehydrogenase) and P450c17 (17alpha-hydroxylase/17,20 lyase) are
      essential for C19 steroid biosynthesis, which is enhanced during adrenarche and
      in PCOS. METHODS: To determine whether the AEDs VPA, carbamazepine (CBZ),
      topiramate (TPM), or lamotrigine (LYG) directly affect the activities of human
      3beta HSDII and P450c17, we added them to yeast expressing human P450c17 or 3beta
      HSDII and assayed enzymatic activities in the microsomal fraction. RESULTS:
      Concentrations of VPA < or = 10 mM had no effect on activities of P450c17;
      however, VPA inhibited 3beta HSDII activity starting at 0.3 mM (reference serum
      unbound concentration, 0.035-0.1 mM) with an IC50 of 10.1 mM. CBZ, TPM, and LTG
      did not influence 3beta HSDII or P450c17 activities at typical reference serum
      unbound concentrations, but did inhibit 3beta HSDII and P450c17 at concentrations
      >10-fold higher. CONCLUSIONS: None of the tested AEDs influenced 3beta HSDII or
      P450c17 activities at concentrations normally used in AED therapy. However, VPA
      started to inhibit 3beta HSDII activity at concentrations 3 times above the
      typical reference serum unbound concentration. Because inhibition of 3beta HSDII
      activity will shift steroidogenesis toward C19 steroid production when P450c17
      activities are unchanged, very high doses of VPA may promote C19 steroid
      biosynthesis, thus resembling PCOS. CBZ, TPM, and LTG influenced 3beta HSDII and
      P450c17 only at toxic concentrations.

PMID- 15730544
TI  - Ictal smile lateralizes to the right hemisphere in childhood epilepsy.
AB  - PURPOSE: To analyze the localizing and lateralizing value of ictal smile (IS) in
      childhood epilepsy. METHODS: Incidence of IS in 309 videotaped seizures of 114
      consecutive patients younger than 12 years with refractory frontal, temporal, or
      posterior cortex epilepsy were assessed. RESULTS: Among patients with right-sided
      epileptogenic zone, 12 (21%) of 57 had IS, whereas in patients with left-sided
      epilepsy, IS occurred only in one patient (1.8%; p < 0.01, chi(2) test). The
      incidence of IS was 11%, 3%, and 26% in the frontal, temporal, and posterior
      cortex subgroups, respectively. Logistic regression revealed that the
      localization of the epileptogenic region in the posterior cortex (p < 0.01),
      focal cortical dysplasia etiology (p = 0.012), and right-sided lateralization (p
      = 0.025) were independently associated with the presence of IS. CONCLUSIONS:
      Childhood IS lateralizes to the right hemisphere and localizes more frequently in
      the posterior cortex epilepsy.

PMID- 15730545
TI  - Epilepsy's role in the historical differentiation of religion, magic, and
      science.
AB  - A distinction between religion, magic, and science has not always been
      recognized. Ancient Greek physicians, in their writings about epilepsy, were
      likely among the first to record the historically important differentiation
      between religion, magic, and science.

PMID- 15730546
TI  - Aura continua.

PMID- 15730547
TI  - It's time to eliminate the term seizure disorder from our lexicon.

PMID- 15730549
TI  - Gamma knife surgery in mesial temporal lobe epilepsy.

PMID- 15730553
TI  - Comparing strategies for United States veterans' mortality ascertainment.
AB  - BACKGROUND: We aimed to determine optimal strategies for complete mortality
      ascertainment comparing death certificates and United States (US) Veterans
      Administration (VA) records. METHODS: We constructed a cohort of California
      veterans who died in fiscal year (FY) 2000 and used VA services the year before
      death. We determined decedent status using California death certificates linked
      to VA utilization data and the VA Beneficiary Identification and Records Locator
      System (BIRLS) death file. We compared the characteristics of decedents who would
      not have been identified by either single source (e.g., VA BIRLS alone or
      California death certificates alone) with the rest of the cohort. RESULTS: A
      total of 8,813 veteran decedents were identified from both VA decedent files and
      death certificates. Of all decedents, 5,698 / 8,813 (65%) veterans were
      identified in both source files, but 2,426 / 8,813 (28%) decedents were not
      identified in VA BIRLS, and 689 / 8,813 (8%) were not identified in death
      certificates. Compared to the rest of the cohort, decedents whose mortality
      status was ascertained through either single source differed by race / ethnicity,
      marital status, and California residence. Clinically, veterans identified from
      either single source had less comorbidity and were less likely to have been users
      of VA inpatient or long term care, but equally or more likely to have been users
      of VA outpatient services. CONCLUSION: As single sources, VA decedent files and
      death certificates each provided an incomplete record, and death ascertainment
      was improved by using both source files. Potential bias may vary depending on
      analytic interest.

PMID- 15730555
TI  - The health workforce crisis in TB control: a report from high-burden countries.
AB  - BACKGROUND: Human resources (HR) constraints have been reported as one of the
      main barriers to achieving the 2005 global tuberculosis (TB) control targets in
      18 of the 22 TB high-burden countries (HBCs); consequently we try to assess the
      current HR available for TB control in HBCs. METHODS: A standard questionnaire
      designed to collect information on staff numbers, skills, training activities and
      current staff shortages at different health service levels was sent to national
      TB control programme managers in all HBCs. RESULTS: Nineteen HBCs (86%) replied,
      and 17 (77%) followed the questionnaire format to provide data. Complete
      information on staff numbers at all service levels was available from nine
      countries and data on skill levels and training were complete in six countries.
      Data showed considerable variations in staff numbers, proportions of trained
      staff, length of courses and quality of training activities. Eleven HBCs had
      developed training materials, many used implementation guidelines for training
      and only three used participatory educational methods. Two countries reported
      shortages of staff at district health facility level, whereas 14 reported
      shortages at central level. There was no apparent association between reported
      staff numbers (and skills) and the country's TB burden or current case detection
      rates (CDR). CONCLUSION: There were few readily available data on HR for TB
      control in HBCs, particularly in the larger ones. The great variations in staff
      numbers and the poor association between information on workforce, proportion of
      trained staff, and length and quality of courses suggested a lack of valid
      information and/or poor data reliability. There is urgent need to support HBCs to
      develop a comprehensive HR strategy involving short-term and long-term HR
      development plans and strengthening their HR planning and management
      capabilities.

PMID- 15730554
TI  - Permissive nicotine regulation as a complement to traditional tobacco control.
AB  - BACKGROUND: Cigarette smoking takes a staggering toll on human health and
      attracts considerable public health attention, yet real solutions seem distant.
      The 2004 Family Smoking Prevention and Tobacco Control Act (US Senate bill S2461)
      would have given the US Food and Drug Administration limited authority to
      regulate cigarettes to "protect the public health." However, such legislation is
      unlikely to substantially reduce smoking or related deaths. DISCUSSION: The past
      500 years of tobacco control efforts demonstrate that nicotine prohibition is a
      practical impossibility for numerous reasons, state revenue being one of the most
      ominous. The FDA already has regulatory authority over pharmaceutical grade
      nicotine products, and requires pharmacists to dispense the most addictive of
      these only with prescriptions. Meanwhile, every corner store can sell far more
      addictive and dangerous cigarettes to any adult. The FDA could immediately
      increase competition between cigarettes and clean nicotine products by approving
      available nicotine products for over-the-counter sales to adults. Similarly
      permissive regulation of cigarettes and addictive nicotine products will reduce
      tobacco use and improve smokers' health, but increase nicotine use in the
      population. Fortunately, restricted youth access and accurate labeling of
      nicotine's absolute risks will dissuade many non-smokers from experimenting with
      it, while accurate depiction of its risks relative to cigarette smoking will
      encourage many smokers to switch. The FDA could take a series of small steps that
      might ultimately replace a large proportion of cigarette smoking with equally
      addictive nicotine products, without risking serious public health setbacks.
      Vaccine, methadone, and injury prevention policies establish relevant public
      health precedents. SUMMARY: Cigarettes, or an equally addictive alternative, will
      be a permanent and common product in most societies. Regulations restricting only
      the safest addictive nicotine products are hard to justify. Addictive nicotine
      compliments other tobacco control strategies. Modern tobacco control policies are
      applicable to addictive nicotine. Controlled trials and test market studies are
      urgently needed to evaluate addictive nicotine as an alternative to smoking.
      Meanwhile, legislators should preserve the Food and Drug Administration's option
      to permit non-prescription sales of addictive nicotine.

PMID- 15730557
TI  - Efficacy of two artemisinin combination therapies for uncomplicated falciparum
      malaria in children under 5 years, Malakal, Upper Nile, Sudan.
AB  - BACKGROUND: The treatment for Plasmodium falciparum malaria in Sudan has been in
      process of change since 2003. Preceding the change, this study aimed to determine
      which artemisinin-based combination therapies is more effective to treat
      uncomplicated malaria in Malakal, Upper Nile, Sudan. METHODS: Clinical trial to
      assess the efficacy of 2 antimalarial therapies to treat P. falciparum infections
      in children aged 6-59 months, in a period of 42 days after treatment. RESULTS: A
      total of 269 children were followed up to 42 days. Artesunate plus
      Sulfadoxine/Pyrimethamine (AS+SP) and Artesunate plus Amodiaquine (AS+AQ) were
      both found to be efficacious in curing malaria infections by rapid elimination of
      parasites and clearance of fever, in preventing recrudescence and suppressing
      gametocytaemia. The combination of AS+SP appeared slightly more efficacious than
      AS+AQ, with 4.4% (4/116) versus 15% (17/113) of patients returning with malaria
      during the 6-week period after treatment (RR = 0.9, 95% CI 0.81-0.96). PCR
      analysis identified only one recrudescence which, together with one other early
      treatment failure, gave efficacy rates of 99.0% for AS+AQ (96/97) and 99.1% for
      AS+SP (112/113). However, PCR results were incomplete and assuming part of the
      indeterminate samples were recrudescent infections leads to an estimated efficacy
      ranging 97-98% for AS+SP and 88-95% for AS+AQ. CONCLUSION: These results lead to
      the recommendation of ACT, and specifically AS+SP, for the treatment of
      uncomplicated falciparum malaria in this area of Sudan. When implemented, ACT
      efficacy should be monitored in sentinel sites representing different areas of
      the country.

PMID- 15730556
TI  - Maternal plasma viral load and neutralizing/enhancing antibodies in vertical
      transmission of HIV: a non-randomized prospective study.
AB  - BACKGROUND: We examined the association and interaction between maternal viral
      load and antibodies in vertical transmission of HIV in a non-randomized
      prospective study of 43 HIV-1 infected pregnant women who attended the San Juan
      City Hospital, Puerto Rico, and their 45 newborn infants. The women and infants
      received antiretroviral therapy. METHODS: A nested PCR assay of the HIV-1
      envelope V3 region and infant PBMC culture were performed to determine HIV status
      of the infants. Maternal and infant plasma were tested for HIV neutralization or
      enhancement in monocyte-derived macrophages. RESULTS: Twelve (26.7%) infants were
      positive by the HIV V3 PCR assay and 3 of the 12 were also positive by culture.
      There was a trend of agreement between high maternal viral load and HIV
      transmission by multivariate analysis (OR = 2.5, CI = 0.92, p = 0.0681). Both
      maternal and infant plasma significantly (p = 0.001 for both) reduced HIV
      replication at 10(-1) dilution compared with HIV negative plasma. Infant plasma
      neutralized HIV (p = 0.001) at 10(-2) dilution but maternal plasma lost
      neutralizing effect at this dilution. At 10(-3) dilution both maternal and infant
      plasma increased virus replication above that obtained with HIV negative plasma
      but only the increase by maternal plasma was statistically significant (p =
      0.005). There were good agreements in enhancing activity in plasma between mother
      infant pairs, but there was no significant association between HIV enhancement by
      maternal plasma and vertical transmission. CONCLUSION: Although not statistically
      significant, the trend of association between maternal viral load and maternal
      infant transmission of HIV supports the finding that viral load is a predictor of
      maternal-infant transmission. Both maternal and infant plasma neutralized HIV at
      low dilution and enhanced virus replication at high dilution. The antiretroviral
      treatments that the women received and the small sample size may have contributed
      to the lack of association between HIV enhancement by maternal plasma and
      vertical transmission.

PMID- 15730560
TI  - Obituary: Yukio Mano (1943-2004).
AB  - Yukio Mano, MD, PhD (1943-2004)Associate Editor, Journal of NeuroEngineering and
      Rehabilitation.

PMID- 15730558
TI  - Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical
      artery resistance in vitro.
AB  - BACKGROUND: The non-thrombotic effects of thrombin in cardiovascular tissues, as
      mediated via the protease activated receptors (PARs), and particularly PAR-1,
      have been the focus of much recent research. The aims of this study were to
      evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP),
      and a PAR-1 antagonist on human umbilical artery tone in vitro. METHODS: Human
      umbilical artery samples were obtained from 17 women at term. Arterial rings were
      suspended under physiologic conditions for isometric recording. The in vitro
      effects of thrombin (0.5 units/mL to 3 units/mL), PAR1-AP TFLLR-NH2 [10(-9) to
      10(-6) M], and PAR-1 antagonist (N-trans cinnamoyl- p-fluoroPhe-p-guanidinoPhe
      Leu-Arg-Orn-NH2) [10(-9) M to 10(-5) M] on umbilical artery tone were measured.
      RESULTS: Both thrombin and TFLLR-NH2 exerted a potent cumulative vasodilatory
      effect on human umbilical artery resistance (P < 0.001). The mean net maximal
      inhibition (MMI) for thrombin was 53.05% (n = 6; SEM = 1.43) at tissue bath
      concentration of 3 units/mL. The MMI with TFLLR-NH2 was 61.50 % (n = 6; SEM =
      1.43) at bath concentration of 10(-6) M. In comparison to vehicle control, the
      PAR-1 antagonist did not show a significant relaxant or contractile effect (P >
      0.05). CONCLUSION: These findings highlight a potential role for thrombin and PAR
      1 receptors in vascular regulation of feto-placental blood flow in normal
      pregnancy, and in association with the vascular lesions associated with IUGR and
      pre-eclampsia.

PMID- 15730559
TI  - Colorectal cancer metastasis: in the surgeon's hands?
AB  - BACKGROUND: Lymphovascular ligation before tumour manipulation during colorectal
      cancer resection is termed the 'no-touch isolation' technique. It aims to reduce
      the intra-operative dissemination of colorectal cancer cells. Recently, the
      detection of circulating tumour cells has been enhanced by molecular biology
      techniques. This paper reviews the evidence for the no-touch isolation technique
      in light of the recent developments in circulating tumour cell detection.
      METHODS: Studies investigating the effect of colorectal cancer surgery on
      circulating tumour cells were identified by a Medline search using the subject
      headings colorectal neoplasms and neoplasm circulating cells together with the
      map term 'no-touch isolation technique'. Further references were obtained from
      key articles. RESULTS: Molecular biological techniques have improved the
      detection of circulating colorectal cancer cells. There is a trend towards
      reduced tumour cell dissemination with the no-touch technique compared with the
      conventional method. However the benefit in terms of improved patient survival
      remains unproven. CONCLUSION: The no-touch isolation technique reduces
      circulating tumour cell dissemination but further work is needed to determine the
      significance of this with regards to patient survival.

PMID- 15730561
TI  - Involvement of beta-chemokines in the development of inflammatory demyelination.
AB  - The importance of beta-chemokines (or CC chemokine ligands - CCL) in the
      development of inflammatory lesions in the central nervous system of patients
      with multiple sclerosis and rodents with experimental allergic encephalomyelitis
      is strongly supported by descriptive studies and experimental models. Our recent
      genetic scans in families identified haplotypes in the genes of CCL2, CCL3 and
      CCL11-CCL8-CCL13 which showed association with multiple sclerosis. Complementing
      the genetic associations, we also detected a distinct regional expression
      regulation for CCL2, CCL7 and CCL8 in correlation with chronic inflammation in
      multiple sclerosis brains. These observations are in consensus with previous
      studies, and add new data to support the involvement of CCL2, CCL7, CCL8 and CCL3
      in the development of inflammatory demyelination. Along with our own data, here
      we review the literature implicating CCLs and their receptors (CCRs) in multiple
      sclerosis and experimental allergic encephalomyelitis. The survey reflects that
      the field is in a rapid expansion, and highlights some of the pathways which
      might be suitable to pharmaceutical interventions.

PMID- 15730562
TI  - Plant viral intergenic DNA sequence repeats with transcription enhancing
      activity.
AB  - BACKGROUND: The geminivirus and nanovirus families of DNA plant viruses have
      proved to be a fertile source of viral genomic sequences, clearly demonstrated by
      the large number of sequence entries within public DNA sequence databases. Due to
      considerable conservation in genome organization, these viruses contain easily
      identifiable intergenic regions that have been found to contain multiple DNA
      sequence elements important to viral replication and gene regulation. As a first
      step in a broad screen of geminivirus and nanovirus intergenic sequences for DNA
      segments important in controlling viral gene expression, we have 'mined' a large
      set of viral intergenic regions for transcriptional enhancers. Viral sequences
      that are found to act as enhancers of transcription in plants are likely to
      contribute to viral gene activity during infection. RESULTS: DNA sequences from
      the intergenic regions of 29 geminiviruses or nanoviruses were scanned for
      repeated sequence elements to be tested for transcription enhancing activity. 105
      elements were identified and placed immediately upstream from a minimal plant
      functional promoter fused to an intron-containing luciferase reporter gene.
      Transient luciferase activity was measured within Agrobacteria-infused Nicotiana
      tobacum leaf tissue. Of the 105 elements tested, 14 were found to reproducibly
      elevate reporter gene activity (>25% increase over that from the minimal promoter
      reporter construct, p < 0.05), while 91 elements failed to increase luciferase
      activity. A previously described "conserved late element" (CLE) was identified
      within tested repeats from 5 different viral species was found to have intrinsic
      enhancer activity in the absence of viral gene products. The remaining 9 active
      elements have not been previously demonstrated to act as functional promoter
      components. CONCLUSION: Biological significance for the active DNA elements
      identified is supported by repeated isolation of a previously defined viral
      element (CLE), and the finding that two of three viral enhancer elements examined
      were markedly enriched within both geminivirus sequences and within Arabidopsis
      promoter regions. These data provide a useful starting point for virologists
      interested in undertaking more detailed analysis of geminiviral promoter
      function.

PMID- 15730563
TI  - A giant subcutaneous leiomyosarcoma arising in the inguinal region.
AB  - BACKGROUND: Subcutaneous leiomyosarcoma is a rare condition that accounts for 1%
      to 2% of all superficial soft tissue malignancies. Approximately 10% of cases
      arise in the trunk, although the extremities are the most commonly affected. CASE
      PRESENTATION: We report herein the case of a 31-year-old man with a subcutaneous
      leiomyosarcoma, measuring 124 x 105 mm, arising in the left inguinal region. A
      wide local excision (with a resection margin >/= 20 mm) was performed.
      Histological examination of the resected specimen revealed a leiomyosarcoma with
      high cellularity and two mitoses per 10 high-power fields. The patient remains
      well with no evidence of disease 5 years and 8 months after the operation.
      CONCLUSION: This is the first reported case of subcutaneous leiomyosarcoma
      arising in the inguinal region and also one of the largest tumors reported. The
      experience of this case and a review of the English-language literature (PubMed,
      National Library of Medicine, Bethesda, MD, USA) suggest that a resection margin
      of >/= 10 mm is recommended when excising this rare tumor.

PMID- 15730565
TI  - A theory of mind investigation into the appreciation of visual jokes in
      schizophrenia.
AB  - BACKGROUND: There is evidence that groups of people with schizophrenia have
      deficits in Theory of Mind (ToM) capabilities. Previous studies have found these
      to be linked to psychotic symptoms (or psychotic symptom severity) particularly
      the presence of delusions and hallucinations. METHODS: A visual joke ToM paradigm
      was employed where subjects were asked to describe two types of cartoon images,
      those of a purely Physical nature and those requiring inferences of mental states
      for interpretation, and to grade them for humour and difficulty. Twenty
      individuals with a DSM-lV diagnosis of schizophrenia and 20 healthy matched
      controls were studied. Severity of current psychopathology was measured using the
      Krawiecka standardized scale of psychotic symptoms. IQ was estimated using the
      Ammons and Ammons quick test. RESULTS: Individuals with schizophrenia performed
      significantly worse than controls in both conditions, this difference being most
      marked in the ToM condition. No relationship was found for poor ToM performance
      and psychotic positive symptomatology, specifically delusions and hallucinations.
      CONCLUSION: There was evidence for a compromised ToM capability in the
      schizophrenia group on this visual joke task. In this instance this could not be
      linked to particular symptomatology.

PMID- 15730564
TI  - Glutamate-induced apoptosis in primary cortical neurons is inhibited by equine
      estrogens via down-regulation of caspase-3 and prevention of mitochondrial
      cytochrome c release.
AB  - BACKGROUND: Apoptosis plays a key role in cell death observed in
      neurodegenerative diseases marked by a progressive loss of neurons as seen in
      Alzheimer's disease. Although the exact cause of apoptosis is not known, a number
      of factors such as free radicals, insufficient levels of nerve growth factors and
      excessive levels of glutamate have been implicated. We and others, have
      previously reported that in a stable HT22 neuronal cell line, glutamate induces
      apoptosis as indicated by DNA fragmentation and up- and down-regulation of Bax
      (pro-apoptotic), and Bcl-2 (anti-apoptotic) genes respectively. Furthermore,
      these changes were reversed/inhibited by estrogens. Several lines of evidence
      also indicate that a family of cysteine proteases (caspases) appear to play a
      critical role in neuronal apoptosis. The purpose of the present study is to
      determine in primary cultures of cortical cells, if glutamate-induced neuronal
      apoptosis and its inhibition by estrogens involve changes in caspase-3 protease
      and whether this process is mediated by Fas receptor and/or mitochondrial signal
      transduction pathways involving release of cytochrome c. RESULTS: In primary
      cultures of rat cortical cells, glutamate induced apoptosis that was associated
      with enhanced DNA fragmentation, morphological changes, and up-regulation of pro
      caspase-3. Exposure of cortical cells to glutamate resulted in a time-dependent
      cell death and an increase in caspase-3 protein levels. Although the increase in
      caspase-3 levels was evident after 3 h, cell death was only significantly
      increased after 6 h. Treatment of cells for 6 h with 1 to 20 mM glutamate
      resulted in a 35 to 45% cell death that was associated with a 45 to 65% increase
      in the expression of caspase-3 protein. Pretreatment with caspase-3-protease
      inhibitor z-DEVD or pan-caspase inhibitor z-VAD significantly decreased glutamate
      induced cell death of cortical cells. Exposure of cells to glutamate for 6 h in
      the presence or absence of 17beta-estradiol or Delta8, 17beta-estradiol (10 nM-10
      microM) resulted in the prevention of cell death and was associated with a
      significant dose-dependent decrease in caspase-3 protein levels, with Delta8,
      17beta-E2 being more potent than 17beta-E2. Protein levels of Fas receptor
      remained unchanged in the presence of glutamate. In contrast, treatment with
      glutamate induced, in a time-dependent manner, the release of cytochrome c into
      the cytosol. Cytosolic cytochrome c increased as early as 1.5 h after glutamate
      treatment and these levels were 5 fold higher after 6 h, compared to levels in
      the untreated cells. Concomitant with these changes, the levels of cytochrome c
      in mitochondria decreased significantly. Both 17beta-E2 and Delta8, 17beta-E2
      reduced the release of cytochrome c from mitochondria into the cytosol and this
      decrease in cytosolic cytochrome c was associated with inhibition of glutamate
      induced cell death. CONCLUSION: In the primary cortical cells, glutamate-induced
      apoptosis is accompanied by up-regulation of caspase-3 and its activity is
      blocked by caspase protease inhibitors. These effects of glutamate on caspase-3
      appear to be independent of changes in Fas receptor, but are associated with the
      rapid release of mitochondrial cytochrome c, which precedes changes in caspase-3
      protein levels leading to apoptotic cell death. This process was differentially
      inhibited by estrogens with the novel equine estrogen Delta8, 17beta-E2 being
      more potent than 17beta-E2. To our knowledge, this is the first study to
      demonstrate that equine estrogens can prevent glutamate-induced translocation of
      cytochrome c from mitochondria to cytosol in rat primary cortical cells.

PMID- 15730566
TI  - Human neuroglobin protein in cerebrospinal fluid.
AB  - BACKGROUND: Neuroglobin is a hexacoordinated member of the globin family of
      proteins. It is predominantly localized to various brain regions and retina where
      it may play a role in protection against ischemia and nitric oxide-induced neural
      injury. Cerebrospinal fluid was collected from 12 chronic regional or systemic
      pain and 5 control subjects. Proteins were precipitated by addition of 50% 0.2 N
      acetic acid, 50% ethanol, 0.02% sodium bisulfite. The pellet was extensively
      digested with trypsin. Peptides were separated by capillary liquid chromatography
      using a gradient from 95% water to 95% acetonitrile in 0.2% formic acid, and
      eluted through a nanoelectrospray ionization interface into a quadrapole - time
      of-flight dual mass spectrometer (QToF2, Waters, Milford, MA). Peptides were
      sequenced (PepSeq, MassLynx v3.5) and proteins identified using MASCOT (R).
      RESULTS: Six different neuroglobin peptides were identified in various
      combinations in 3 of 9 female pain subjects, but none in male pain, or female or
      male control subjects. CONCLUSION: This is the first description of neuroglobin
      in cerebrospinal fluid. The mechanism(s) leading to its release in chronic pain
      states remain to be defined.

PMID- 15730567
TI  - In touch with robotics: neurosurgery for the future.
AB  - The introduction of multiple front-end technologies during the past quarter
      century has generated an emerging futurism for the discipline of neurological
      surgery. Driven primarily by synergistic developments in science and engineering,
      neurosurgery has always managed to harness the potential of the latest technical
      developments. Robotics represents one such technology. Progress in development of
      this technology has resulted in new uses for robotic devices in our discipline,
      which are accompanied by new potential dangers and inherent risks. The recent
      surge in robot-assisted interventions in other disciplines suggests that this
      technology may be considered one of a spectrum of frontier technologies poised to
      fuel the development of neurosurgery and consolidate the era of minimalism. On a
      more practical level, if the introduction of robotics in neurosurgery proves
      beneficial, neurosurgeons will need to become facile with this technology and
      learn to harness its potential so that the best surgical results may be achieved
      in the least invasive manner. This article reviews the role of robotic technology
      in the context of neurosurgery.

PMID- 15730568
TI  - Robotic long-distance telementoring in neurosurgery.
AB  - OBJECTIVE: To test the feasibility of long-distance telementoring in neurosurgery
      by providing subspecialized expertise in real time to another neurosurgeon
      performing a surgical procedure in a remote location. METHODS: A robotic
      telecollaboration system (Socrates; Computer Motion, Inc., Santa Barbara, CA)
      capable of controlling the movements of a robotic arm, of handling two-way video,
      and of audio communication as well as transmission of neuronavigational data from
      the remote operating room was used for the telementoring procedures. Four
      integrated services digital network lines with a total speed of transmission of
      512 kilobytes per second provided telecommunications between a large academic
      center (Halifax, Nova Scotia) and a community-based center (Saint John, New
      Brunswick) located 400 km away. RESULTS: Long-distance telementoring was used in
      three craniotomies for brain tumors, a craniotomy for an arteriovenous
      malformation, a carotid endarterectomy, and a lumbar laminectomy. There were no
      surgical complications during the procedures, and all patients had uneventful
      outcomes. The neurosurgeons in the remote location believed that the input from
      the mentors was useful in all of the cases and was crucial in the removal of a
      mesial temporal lobe glioma and resection of an occipital arteriovenous
      malformation. CONCLUSION: Our initial experience with long-distance robotic
      assisted telementoring in six cases indicates that telementoring is feasible,
      reliable, and safe. Although still in its infancy, telementoring has the
      potential to improve surgical care, to enhance neurosurgical training, and to
      have a major impact on the delivery of neurosurgical services throughout the
      world.

PMID- 15730569
TI  - Thrombotic intracranial aneurysms: classification scheme and management
      strategies in 68 patients.
AB  - OBJECTIVE: Thrombotic aneurysms are a diverse collection of complex aneurysms
      characterized by organized intraluminal thrombus and solid mass. Consequently,
      their treatment often requires techniques other than conventional clipping, such
      as thrombectomy with clip reconstruction or bypass with parent artery occlusion.
      A single-surgeon experience with thrombotic aneurysms was analyzed to determine
      optimal treatment strategies. A classification scheme was devised on the basis of
      aneurysm, thrombus, and lumen morphology to relate these anatomic features to
      surgical therapy. METHODS: Sixty-eight patients with thrombotic aneurysms were
      managed during a period of 6.25 years. Thrombotic aneurysms were classified into
      six types: concentric (n = 17, 25%), eccentric (n = 14, 21%), lobulated (n = 2,
      3%), complete (n = 2, 3%), canalized (n = 17, 25%), and coiled (n = 16, 24%).
      RESULTS: Aneurysm management consisted of direct clipping (n = 22, 32%),
      thrombectomy-clip reconstruction (n = 18, 26%), bypass-occlusion (n = 20, 29%),
      other (n = 6, 9%), or observation (n = 2, 3%). Complete angiographic obliteration
      was achieved in 97% of patients, and 47% of aneurysms were thrombectomized. The
      surgical mortality rate was 6%, and the permanent neurological morbidity rate was
      7%. Overall, 87% of patients were improved or unchanged at follow-up, with 79%
      reaching a Glasgow Outcome Scale score of 5 or 4. Management strategy was
      influenced by thrombotic aneurysm type, but patient outcome was not. The best
      results were observed in patients treated with direct clipping and bypass
      occlusion. CONCLUSION: Despite their solid mass, one-third of thrombotic
      aneurysms can be treated surgically with conventional clipping. Direct clipping
      is associated with the best surgical results, and the proposed classification
      scheme identifies thrombotic aneurysms that may be clippable. Patients with
      unclippable thrombotic aneurysms had more favorable results when treated with
      bypass and aneurysm occlusion than with thrombectomy and clip reconstruction. The
      classification scheme may provide conceptual clarity and therapeutic guidance
      with preoperative and intraoperative decision making.

PMID- 15730570
TI  - Analysis of intraoperative rupture in the surgical treatment of 1694 saccular
      aneurysms.
AB  - OBJECTIVE: Intraoperative rupture (IOR) of an aneurysm is a known risk in the
      surgical management of intracranial aneurysms. The purpose of this study was to
      determine the incidence of IOR in a modern surgical series and to assess which
      factors bear upon it. METHODS: This study retrospectively examined 1269 patients
      with saccular aneurysms treated surgically between 1986 and 1998. Three vascular
      neurosurgeons performed 1435 operations on 1694 aneurysms. Multiple factors,
      including the magnitude and time of occurrence of IOR, aneurysm location,
      subarachnoid hemorrhage, timing of surgery, and use of temporary occlusion, were
      analyzed. RESULTS: There were 113 instances of IOR (7.9% per surgery; 6.7% per
      aneurysm; 8.9% per patient). If the 59 "minor leaks" are excluded (as in
      previously published reports), the incidence becomes 3.8% per surgery, 3.2% per
      aneurysm, and 4.3% per patient. Posteroinferior cerebellar artery and anterior
      and posterior communicating artery aneurysms were more liable to rupture
      intraoperatively. The IOR rate was greater in ruptured than unruptured aneurysms
      (10.7 versus 1.2%, P < 0.0001). There was a lower rate of IOR in operations using
      temporary arterial occlusion (3.1 versus 8.6%, P < 0.0001). The occurrence of IOR
      for early surgery was not significantly higher than for surgery performed more
      than 3 days after subarachnoid hemorrhage (11.1 versus 10.0%, P = 0.6234).
      CONCLUSION: The rate of significant IOR can be kept low. Aneurysm location,
      subarachnoid hemorrhage, and temporary arterial occlusion seem to be important
      factors affecting the incidence of IOR.

PMID- 15730571
TI  - Surgical treatment for aneurysmal subarachnoid hemorrhage in the 8th and 9th
      decades of life.
AB  - OBJECTIVE: Industrialized countries are facing a rapid increase of their senior
      populations. Consequently, the number of elderly patients with aneurysmal
      subarachnoid hemorrhage is increasing. The purpose of this study was to assess
      the results of surgical repair for ruptured aneurysm in elderly patients.
      METHODS: We retrospectively investigated elderly patients (ages 70-89 yr) who
      were undergoing surgical treatment for ruptured aneurysm during the 15-year
      period 1988 to 2002 and compared patients in the 8th and 9th decades of life.
      Generally, patients were treated surgically within 72 hours after ictus. RESULTS:
      Of the total of 2835 patients, there were 509 patients (18.0% of total patients)
      in the 8th decade and 99 patients (3.5%) in the 9th decade of life. Because data
      were incomplete and patients who received ventricular drainage or
      ventriculoperitoneal shunt without aneurysmal repair were excluded, 449 and 89
      patients in the 8th and 9th decades of life, respectively, were analyzed. No
      differences in sex, preoperative grade, preoperative computed tomographic
      findings, location of aneurysm, and aneurysm size were observed between the two
      decades. Preoperative grade and computed tomographic findings were predictors of
      favorable outcomes in the 8th and 9th decades. Patient age was a significant
      predictor of outcome in the 8th but not in the 9th decade. CONCLUSION: To the
      best of our knowledge, this study is the largest series of its kind to date.
      Advanced age alone does not exclude adequate surgical repair in patients with
      aneurysmal rupture in the 9th decade of life.

PMID- 15730572
TI  - Effect of prior statin use on functional outcome and delayed vasospasm after
      acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study.
AB  - OBJECTIVE: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which
      exhibit beneficial cerebrovascular effects by modulating inflammation and nitric
      oxide production, have not been evaluated in acute aneurysmal subarachnoid
      hemorrhage (SAH) patients. The effect of prior statin use on 14-day functional
      outcome and on prevention of vasospasm-induced delayed cerebral ischemia (DCI) or
      stroke during hospitalization was analyzed. METHODS: We conducted a 1:2 matched
      (age, admission Hunt and Hess grade, vascular disease/risk history) cohort study
      of 20 SAH patients on statins and 40 SAH controls. The primary outcome was
      functional outcome at 14 days (Modified Lawton Physical Self-Maintenance Scale
      and Barthel Index scale scores). Secondary outcomes were 14-day mortality,
      Modified Rankin Scale score, DCI, DCI supported by angiography/transcranial
      Doppler [TCD], cerebral infarctions of any type, and TCD highest mean velocity
      elevation. RESULTS: Statin users demonstrated a significant protective effect on
      14-day Barthel Index scale and Modified Lawton Physical Self-Maintenance Scale
      scores (77 +/- 10 versus 39 +/- 8, P = 0.003; 12 +/- 7 versus 19 +/- 9, P = 0.03,
      respectively). Moreover, statin users demonstrated a significantly lower
      incidence of DCI and DCI supported by angiography/TCD (10% versus 43%, P = 0.02;
      5% versus 35%, P = 0.01, respectively), cerebral infarctions of any type (25%
      versus 63%, P = 0.01), and baseline-to-final TCD highest mean velocity change of
      50 cm/s or greater (18% versus 51%, P = 0.03). CONCLUSION: SAH statin users
      demonstrated significant improvement in 14-day functional outcome, a
      significantly lower incidence of DCI and cerebral infarctions of any type, as
      well as prevention of TCD highest mean velocity elevation. However, we did not
      find a significant statin impact on mortality or global outcome (Modified Rankin
      Scale) in this small sample. This study provides clinical evidence for the
      potential therapeutic benefit of statins after acute SAH.

PMID- 15730573
TI  - Effect of presenting hemorrhage on outcome after microsurgical resection of brain
      arteriovenous malformations.
AB  - OBJECTIVE: We hypothesized that patients with unruptured arteriovenous
      malformations (AVMs) at presentation have an increased risk of deterioration
      compared with patients with ruptured AVMs. METHODS: A consecutive series of 224
      patients treated microsurgically by a single neurosurgeon during a period of 6.4
      years was analyzed. Initial hemorrhagic presentation was the primary predictor
      variable. Neurological outcomes were assessed by use of the Modified Rankin Scale
      (MRS) and Glasgow Outcome Scale (GOS), and logistic regression identified
      predictors of deterioration at follow-up (mean duration, 1.3 yr) relative to
      baseline before any intervention. RESULTS: Overall, 120 patients (54%) presented
      with hemorrhage, and all 224 patients underwent microsurgical resection. Complete
      resection was achieved in 220 patients (98%). According to GOS score, 13 patients
      (5.8%) deteriorated; according to MRS score, 45 patients (20.1%) deteriorated.
      Fifteen patients (6.7%) died. Hemorrhagic presentation was associated with
      improved outcomes, with a mean change in MRS score of +0.89 in patients with
      ruptured AVMs and -0.38 in patients with unruptured AVMs (P < 0.001). The final
      mean MRS scores in patients with unruptured AVMs were better than those in
      patients with ruptured AVMs (1.44 versus 1.90; P = 0.048). Presentation with an
      unruptured AVM was a predictor of worsening MRS score (odds ratio, 2.33; 95%
      confidence interval, 1.3-4.3; P = 0.006) but not of worsening GOS score.
      CONCLUSION: Presentation with AVM hemorrhage is an underappreciated predictor of
      outcome after therapy that includes microsurgical resection. Patients with
      ruptured AVMs tended to have deficits at presentation and generally improved
      after surgery, whereas patients with unruptured AVMs tended to have normal or
      nearly normal neurological function at presentation and were susceptible to
      worsening, albeit slight, as measured by MRS scores. Sensitive outcome measures
      such as MRS detect subtle symptoms and impairments missed by coarser measures
      such as GOS. Patients should be counseled that the risks associated with elective
      resection of unruptured AVMs may be higher than recognized previously.
      Hemorrhagic brain injury and its secondary effects may mask this surgical
      morbidity.

PMID- 15730574
TI  - Angiographic changes in venous drainage of cavernous sinus dural arteriovenous
      fistulae after palliative transarterial embolization or observational management:
      a proposed stage classification.
AB  - OBJECTIVE: We assessed whether angiographic changes in venous drainage patterns
      occur over time in cavernous sinus dural arteriovenous fistulae (dAVFs) without a
      complete cure. METHODS: We classified 65 cavernous sinus dAVFs into three types
      on the basis of initial angiographic findings. In Type 1, both anterior and
      posterior drainage routes were open; in Type 2, the posterior drainage route was
      closed, whereas the anterior drainage route was open; and in Type 3, both the
      posterior and anterior drainage routes were closed. RESULTS: Of the 65 dAVFs, 40
      were of Type 1, 21 of Type 2, and 4 of Type 3. During the follow-up period, 17 of
      the dAVFs that were treated palliatively with transarterial embolization (n = 11)
      or monitored without therapy (n = 6) demonstrated angiographic changes. In these
      11 patients, there was a change in the venous drainage pattern from Type 1 to
      Type 2 (n = 5), from Type 2 to Type 3 (n = 3), and from Type 1 to Type 3 (n = 3).
      One of 11 had a conversion into a lesion with cortical venous drainage. The
      remaining 6 dAVFs (4 with observational management, 2 with transarterial
      embolization) demonstrated closure of the fistula; in 5 of these, the affected
      cavernous sinus was not depicted on follow-up angiograms. CONCLUSION: In some
      cavernous sinus dAVFs with palliative transarterial embolization or observational
      management, there was a change in the venous drainage patterns, consisting of a
      decrease in the number of venous drainage routes. There was a trend for the
      posterior route to close before the anterior drainage or cortical drainage route.
      This suggests the occurrence of a staged progression in a regular direction in
      cavernous sinus dAVFs. Without treatment aiming at a complete cure, most
      cavernous sinus dAVFs can behave benignly, with a low possibility of development
      of cortical venous reflux during follow-up.

PMID- 15730575
TI  - Characterization of hemangioblastomas of spinal nerves.
AB  - OBJECTIVE: Hemangioblastoma is classified as a benign tumor of the central
      nervous system. Peripheral nervous system hemangioblastomas to date have been
      described only in a few case reports. Experience in treating patients with these
      rare lesions, which harbor diagnostic and therapeutic pitfalls, is limited.
      METHODS: To characterize these lesions better, we reviewed our hemangioblastoma
      database for patients who underwent surgery for extradural hemangioblastoma of
      the spinal nerve. RESULTS: Between 1983 and 2003, six patients underwent surgery
      for spinal nerve hemangioblastomas at our institution. These tumors occurred in
      2% of all patients with hemangioblastomas of the central nervous system, or 6% of
      all patients with spinal hemangioblastomas. The occurrence did not differ in von
      Hippel-Lindau disease cases versus sporadic cases. Radiographically, the tumors
      easily could be mistaken for schwannomas or metastases; however, they did have
      some typical features. If a hemangioblastoma was not suspected primarily, profuse
      bleeding could complicate surgery. Most of the tumors arose from the dorsal
      sensory fascicles. The vascular supply was from extradural circulation. In
      general, the surgical outcome of these lesions was good, and permanent
      neurological deficit was rare. However, local recurrence was observed in three of
      six patients. CONCLUSION: These tumors harbor diagnostic and therapeutic
      pitfalls. In general, the tumors are surgically more challenging, and clinically
      significant bleeding as well as local tumor recurrence is more common than in
      intradural hemangioblastomas, mostly because of the frequency of incorrect
      initial radiographic diagnosis. We suggest that because of the surgical
      consequences, hemangioblastoma should always be considered to be an important
      radiological differential diagnosis for nerve sheath tumors. Angiography can
      bring clarification to ambiguous cases.

PMID- 15730576
TI  - Clinical characteristics of spinal nerve sheath tumors: analysis of 149 cases.
AB  - OBJECTIVE: Spinal nerve sheath tumors arise from the spinal nerve root and grow
      along it. There are two sites at which the growth of a tumor is restricted: the
      dural aperture for the spinal nerve root and the intervertebral foramen. This
      article describes the growth pattern of a spinal nerve sheath tumor along the
      spinal nerve root at various spinal levels. METHODS: We retrospectively reviewed
      the records for 149 patients with spinal nerve sheath tumors who were treated
      between 1980 and 2001. Of these, 176 resected tumors were classified into five
      groups according to the relationship to the dura mater and/or the intervertebral
      foramen. RESULTS: Strictly intradural tumors compose 8% of nerve sheath tumors of
      the first two cervical nerve roots. The percentage of these tumors increased
      gradually from the high cervical region to the thoracolumbar region, where it was
      more than 80%. In contrast, the percentage of strictly extradural tumors
      gradually decreased from the rostral portion to the caudal portion. Similarly, a
      percentage of tumors extending outside the spinal canal decreased from the
      rostral portion to the caudal portion. These changes of the growth pattern may be
      explained by the anatomic features of the spinal nerve roots, which have a longer
      intradural component at the more caudal portion of the spinal axis. CONCLUSION:
      The anatomic relationship of a nerve sheath tumor with the dura mater and the
      intervertebral foramen varies depending on the level of the tumor. This knowledge
      may help us to create a strategy for total resection of a nerve sheath tumor.

PMID- 15730577
TI  - Nonoperative management of vertical C2 body fractures.
AB  - OBJECTIVE: To estimate the incidence and to describe the clinical results of the
      nonoperative management of vertical C2 body fractures. METHODS: An 8-year
      retrospective review of upper cervical spine injuries from the registry of a
      level I trauma center identified 21 patients with a vertical C2 body fracture.
      RESULTS: Sixteen coronally oriented Type 1 vertical C2 body fractures and 5
      sagittally oriented Type 2 vertical C2 body fractures were identified. These
      fractures account for approximately 10% of the upper cervical spine fractures
      identified over this period of time. One elderly patient with a Type 1 fracture
      died as a result of pneumonia, and two patients with Type 2 fractures died from
      severe closed-head injuries. One patient had evidence of spinal cord injury. This
      was not related to the C2 body fracture but rather to a subaxial cervical spine
      injury. Of the surviving 18 patients, all were managed nonoperatively (with
      external orthoses) and showed evidence of fusion (union of fracture fragments) at
      the time of the last follow-up. CONCLUSION: Vertical C2 body fractures are not
      rare injuries and can account for up to 10% of upper cervical spine injuries. In
      general, vertical C2 body fractures are amenable to nonoperative treatment with
      external orthoses.

PMID- 15730578
TI  - Prospective randomized controlled study comparing simple decompression versus
      anterior subcutaneous transposition for idiopathic neuropathy of the ulnar nerve
      at the elbow: Part 1.
AB  - OBJECTIVE: The main objective of this study was to compare the clinical outcome
      of participants treated by simple decompression (SD) of the ulnar nerve versus
      anterior subcutaneous transposition (AST). METHODS: A prospective randomized
      controlled study was performed. Three hundred forty participants were referred to
      our institution between March 1999 and July 2002. One hundred fifty-two patients
      met the inclusion criteria and were randomized into two surgical groups: 75 were
      assigned to SD, and 77 were assigned to AST. Participants were followed for 1
      year after surgery. The main outcome measure was clinical outcome 1 year after
      surgery. RESULTS: An excellent or good result was obtained in 49 of 75
      participants who underwent SD and in 54 of 77 participants undergoing AST. The
      difference was not statistically significant. However, the complication rate was
      statistically lower in the SD group (9.6%) compared with the AST group (31.1%)
      (risk ratio, 0.32; 95% confidence interval, 0.14-0.69). Duration of symptoms,
      (sub)luxation of the ulnar nerve, and severity of the complaints did not
      influence outcome. CONCLUSION: Surgery for ulnar neuropathy at the elbow is
      effective. The outcomes of SD and AST are equivalent, except for the complication
      rate. Because the intervention is simpler and associated with fewer
      complications, SD is advised, even in the presence of (sub)luxation.

PMID- 15730579
TI  - Simple decompression or anterior subcutaneous transposition for ulnar neuropathy
      at the elbow: a cost-minimization analysis--Part 2.
AB  - OBJECTIVE: A randomized controlled trial was reported recently, in which simple
      decompression and anterior subcutaneous transposition were compared for treatment
      of ulnaropathy at the elbow. Clinically, both surgical options seem to be equally
      effective. The objective of this study is to compare the costs, from a societal
      standpoint, of simple decompression versus anterior subcutaneous transposition in
      Euros. METHODS: Published and unpublished data from a randomized controlled trial
      that compared simple decompression and anterior subcutaneous transposition were
      used. The investigators tabulated the actual costs incurred for professional
      fees, use of the operating room, duration of sick leave, reintervention, and
      treatment of complications directly related to the surgical treatment. RESULTS:
      The total costs per group and per patient were statistically significantly less
      for those treated with simple decompression. The total median costs per patient
      were 1124 Euros for simple decompression and 2730 Euros for anterior subcutaneous
      transposition. The main difference was in the costs related to sick leave, which
      is significantly shorter for simple decompression. There also was a statistically
      significant difference in operation time in favor of simple decompression. A
      remarkable finding was that paid workers in both treatment groups returned to
      work much later than unpaid workers. CONCLUSION: Although clinically equally
      effective, simple decompression was associated with lower cost than anterior
      subcutaneous transposition for the treatment of ulnar neuropathy at the elbow.
      Compared with anterior subcutaneous transposition, we recommend simple
      decompression for the treatment of idiopathic ulnar neuropathy at the elbow.

PMID- 15730580
TI  - Percutaneous retrogasserian glycerol rhizotomy in the treatment of tic douloureux
      associated with multiple sclerosis.
AB  - OBJECTIVE: Patients with multiple sclerosis (MS) have a relatively high incidence
      of tic douloureux (TD) and often do not tolerate medical therapy well. The
      minimally invasive nature of percutaneous retrogasserian glycerol rhizotomy
      (PRGR) renders it ideal for first-line surgical treatment of TD. We sought to
      ascertain the benefits of PRGR in patients with MS and to determine whether
      hypalgesia after PRGR correlates with efficacy. METHODS: We assessed 97 glycerol
      procedures performed in 53 patients followed prospectively for treatment of TD
      associated with MS. Factors assessed included degree of pain relief,
      postoperative hypalgesia, procedural morbidity, medication use, time to pain
      recurrence, and number and type of subsequent procedures. RESULTS: Complete pain
      relief was obtained in 78% of patients after the initial glycerol injection, and
      partial relief was obtained in 13% of patients. Long-term follow-up (mean, 81 mo)
      demonstrated a recurrence rate of 59%, with a mean time to recurrence of 17
      months. Actuarial recurrence rates were 50% at 12 months and 60% at 24 months.
      Twenty-four patients underwent a second or subsequent PRGR for recurrent pain and
      achieved similar rates of pain relief and time to recurrence. Facial sensory loss
      was associated with a higher likelihood of pain relief (P < 0.05), with longer
      time to pain recurrence (P < 0.05), and with decreased use of medication after
      surgery (P < 0.01.) CONCLUSION: PRGR is an effective, low-morbidity surgical
      procedure in the management of TD complicating MS. The presence of facial sensory
      loss after PRGR is associated with prolonged efficacy.

PMID- 15730581
TI  - Surgical management of petroclival meningiomas: defining resection goals based on
      risk of neurological morbidity and tumor recurrence rates in 137 patients.
AB  - OBJECTIVE: Meningiomas arising from the petroclival region remain a challenging
      surgical problem. Because of the substantial risk of neurological morbidity,
      uniformly pursuing a gross total resection (GTR) to minimize tumor recurrence
      rates may not be justified. We sought to define optimal resection goals based on
      risk factors for postoperative neurological morbidity and tumor recurrence rates.
      METHODS: This series represents our experience with 137 meningiomas arising from
      the petroclival region resected between June 1993 and October 2002. There were 38
      male and 99 female patients with a mean age of 53 years. RESULTS: GTR was
      achieved in 40% of patients, and near total resection (NTR) was achieved in 40%
      of patients. One operative death occurred. Twenty-six percent of patients
      experienced new postoperative cranial nerve deficits, paresis, or ataxia when
      assessed at a mean follow-up of 8.3 months. The risk of cranial nerve deficits
      increased with prior resection (P < 0.001), preoperative cranial nerve deficit (P
      = 0.005), tumor adherence to neurovascular structures (P = 0.046), and fibrous
      tumor consistency (P = 0.005). The risk of paresis or ataxia increased with prior
      resection (P = 0.001) and tumor adherence (P = 0.045). Selective NTR rather than
      GTR in patients with adherent or fibrous tumors significantly reduced the rate of
      neurological deficits. Radiographic recurrence or progression occurred in 17.6%
      of patients at a mean follow-up of 29.8 months. Tumor recurrence rates after GTR
      and NTR did not differ significantly (P = 0.111). CONCLUSION: Intraoperatively
      defined tumor characteristics played a critical role in identifying the subset of
      patients with an increased risk of postoperative deficits. By selectively
      pursuing an NTR rather than a GTR, neurological morbidity was reduced
      significantly without significantly increasing the rate of tumor recurrence.

PMID- 15730582
TI  - Suboccipital retrosigmoid approach for removal of vestibular schwannomas: facial
      nerve function and hearing preservation.
AB  - In this report, we discuss the pertinent bony, arachnoid, and neurovascular
      anatomy of vestibular schwannomas that has an impact on the surgical technique
      for removal of these tumors, with the goal of facial nerve and hearing
      preservation. The surgical technique is described in detail starting with
      anesthesia, positioning, and neurophysiological monitoring and continuing with
      the exposure, technical nuances of tumor removal, hemostasis, and closure.
      Positive prognostic factors for hearing preservation are also highlighted.

PMID- 15730583
TI  - Postischemic reperfusion: ultrastructural blood-brain barrier and hemodynamic
      correlative changes in an awake model of transient forebrain ischemia.
AB  - OBJECTIVE: In nonrecovery models of cerebral ischemia, blood-brain barrier (BBB)
      and cerebral blood flow (CBF) changes are known to occur during reperfusion. It
      is unknown, however, whether those CBF and BBB alterations occur after brief,
      transient ischemia with neurological recovery. The purpose of this study was to
      characterize the time course of CBF and BBB ultrastructural changes during
      reperfusion in an awake, recovery model of transient global forebrain ischemia
      (GFI). METHODS: Forty-five adult Sprague-Dawley rats were subjected, while awake,
      to 10 minutes of GFI by the nine-vessel occlusion method. Thirty-five age-matched
      animals composed a sham-operated group. Normal control (n = 5), sham-operated (n
      = 5), and nine-vessel occlusion/reperfusion (n = 15) rats were selected for
      ultrastructural analysis. Electroencephalography was performed, and CBF, mean
      arterial blood pressure, and intracranial pressure were measured during ischemia
      and reperfusion up to 24 hours. Quantitative morphological analysis of cortical
      BBB capillaries was performed by transmission electron microscopy at the same
      time points at which specific CBF changes occurred during reperfusion. RESULTS:
      CBF decreased to 6% of preocclusion values during GFI. This correlated with coma
      and decerebrate rigidity. During reperfusion, short-lived hyperemia (225 +/- 18%,
      P < 0.001) was characterized by increased intracranial pressure (28.3 +/- 2.6 mm
      Hg, P < 0.001) and isoelectric electroencephalogram. This was followed by
      hypoperfusion, which reached a nadir of 59.7% (59.7 +/- 8.8%, P < 0.01) from
      baseline by 90 minutes. At this time point, the electroencephalogram recovered,
      and intracranial pressure and mean arterial blood pressure showed no
      abnormalities. By 8.5 hours, CBF returned to normal, and this coincided with
      complete recovery of the animal. Ultrastructural BBB analysis revealed astrocyte
      end-foot process edema and patent capillaries during hyperemia. Severe
      interstitial BBB edema and capillary lumen collapse was observed during
      hypoperfusion. Detachment and migration of pericytes was observed during
      hypoperfusion and beyond. CONCLUSION: A biphasic CBF response is elicited during
      reperfusion after brief nonlethal GFI under awake conditions.

PMID- 15730584
TI  - Cerebral oxidative stress and depression of energy metabolism correlate with
      severity of diffuse brain injury in rats.
AB  - OBJECTIVE: The combined effect of traumatic brain injury (TBI) and secondary
      insult on biochemical changes of cerebral tissue is not well known. For this
      purpose, we studied the time-course changes of parameters reflecting ROS-mediated
      oxidative stress and modifications of cell energy metabolism determined in rats
      subjected to cerebral insult of increasing severity. METHODS: Rats were divided
      into four groups: 1) sham-operated, 2) subjected to 10 minutes of hypoxia and
      hypotension (HH), 3) subjected to severe diffuse TBI, and 4) subjected to severe
      diffuse TBI + HH. Rats were killed at different times after injury, and analyses
      of malondialdehyde, ascorbate, high-energy phosphates, nicotinic coenzymes,
      oxypurines, nucleosides, and N-acetylaspartate (NAA) were made by high
      performance liquid chromatography on whole-brain tissue extracts. RESULTS: Data
      indicated a close relationship between degree of oxidative stress and severity of
      brain insult, as evidenced by the highest malondialdehyde values and lowest
      ascorbate levels in rats subjected to TBI + HH. Similarly, modifications of
      parameters related to cell energy metabolism were modulated by increasing
      severity of brain injury, as demonstrated by the lowest values of energy charge
      potential, nicotinic coenzymes, and NAA and the highest levels of oxypurines and
      nucleosides recorded in TBI + HH rats. Both the intensity of oxidative stress
      mediated cerebral damage and perturbation of energy metabolism were minimally
      affected in rats subjected to HH only. CONCLUSION: These results showed that the
      severity of brain insult can be graded by measuring biochemical modifications,
      specifically, reactive oxygen species-mediated damage, energy metabolism
      depression, and NAA, thereby validating the rodent model of closed-head diffuse
      TBI coupled with HH and proposing NAA as a marker with diagnostic relevance to
      monitor the metabolic state of postinjured brain.

PMID- 15730586
TI  - From trephination to tailored resection: neurosurgery in Germany before World War
      II.
AB  - Evidence exists that trephination was performed in Germany as early as the Stone
      Age. Late medieval barber surgeons further developed instruments and techniques
      for this procedure. Various surgeons performed individual cranial operations
      before the 1870s, and neurosurgery evolved as a distinct discipline in Germany
      around 1934. Before the 20th century, most cranial operations in Germany, as in
      other European countries, were performed for trauma. Since approximately 1870, a
      few individuals with a devoted interest in surgery of the nervous system have
      developed operative techniques for the brain and spinal cord. Wilhelm Wagner,
      Fedor Krause, Ernst von Bergmann, and Otfrid Foerster were among these pioneers.
      Through independent research based on careful clinical observation, these
      physicians contributed significantly to an understanding of the pathophysiology
      of nervous system disorders that could be treated surgically. They designed
      techniques, such as those used for intracranial pressure regulation, and
      developed operative procedures, such as the osteoplastic flap of Wagner, and
      cortical stimulation, which was performed by Krause and Foerster.

PMID- 15730587
TI  - Reflections: a historical vignette.
AB  - vignette is a diminutive of vigne (vine) and at first was used in the form of a
      vine branch, e.g., to begin or end a chapter in a book or to frame a medieval
      miniature. By extension, it has taken on the meaning of image. This stereotactic
      vignette is by no means a historical account of functional stereotactic
      neurosurgery in the 1960s, but it is through a description of the evolution of my
      relationships with close colleagues in those early years that I attempt to
      recreate the atmosphere and medical dreams of this group of doctors, who were
      somewhat outside the mainstream of neurosurgery at that time.

PMID- 15730588
TI  - Cervical spine meningioma presenting as otalgia: case report.
AB  - OBJECTIVE AND IMPORTANCE: Cervical spine meningiomas have not been reported to
      present as otalgia. It is important to include otalgia in the differential
      diagnosis and workup, especially when more common causes of ear pain have been
      excluded. CLINICAL PRESENTATION: A 66-year-old woman presented to her primary
      care physician with severe ear pain. She underwent routine diagnostic testing and
      eventually was referred to a neurologist. After conservative management failed,
      the patient underwent cervical spine magnetic resonance imaging, which revealed a
      large meningioma encompassing C2-C3. INTERVENTION: The patient underwent a
      cervical laminectomy with complete resection of the tumor. She experienced
      immediate postoperative resolution of her symptoms. CONCLUSION: This case
      illustrates the importance of aggressive evaluation of otalgia when routine
      diagnostic studies are inconclusive. Cervical meningiomas are associated with
      significant potential morbidity and should be excluded early in the diagnostic
      process.

PMID- 15730585
TI  - Cyclooxygenase-2-specific inhibitor improves functional outcomes, provides
      neuroprotection, and reduces inflammation in a rat model of traumatic brain
      injury.
AB  - OBJECTIVE: Increases in brain cyclooxygenase-2 (COX2) are associated with the
      central inflammatory response and with delayed neuronal death, events that cause
      secondary insults after traumatic brain injury. A growing literature supports the
      benefit of COX2-specific inhibitors in treating brain injuries. METHODS: DFU [5,5
      dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5)H)-furanone] is a third
      generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg
      intraperitoneally, twice daily for 3 d) were initiated either before or after
      traumatic brain injury in a lateral cortical contusion rat model. RESULTS: DFU
      treatments initiated 10 minutes before injury or up to 6 hours after injury
      enhanced functional recovery at 3 days compared with vehicle-treated controls.
      Significant improvements in neurological reflexes and memory were observed. DFU
      initiated 10 minutes before injury improved histopathology and altered eicosanoid
      profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the
      brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2
      immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This
      treatment also decreased the total number of activated caspase-3-immunoreactive
      cells in the injured cortex and hippocampus, significantly reducing the number of
      activated caspase-3-immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg
      amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more
      than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2
      arachidonoyl glycerol, a neuroprotective endocannabinoid, in the injured brain.
      CONCLUSION: These improvements, particularly when treatment began up to 6 hours
      after injury, suggest exciting neuroprotective potential for COX2 inhibitors in
      the treatment of traumatic brain injury and support the consideration of Phase
      I/II clinical trials.

PMID- 15730589
TI  - Ossification of the ligamentum flavum as a result of fluorosis causing
      myelopathy: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Ossification of the ligamentum flavum (OLF) is
      increasingly being recognized as a cause of myeloradiculopathy. However, the
      cause of such OLF has been identified only occasionally. The purpose of this case
      report is to highlight one more cause of OLF causing myelopathy. CLINICAL
      PRESENTATION: Two middle-aged men residing in an area endemic for fluorosis
      presented with the insidious onset of myelopathy. Clinical examination revealed
      evidence of thoracic cord compression in both patients. Plain x-rays revealed
      markedly increased bone density characteristic of fluorosis. Magnetic resonance
      imaging revealed OLF in the lower thoracic region causing cord compression (at
      one level in the first patient and at three consecutive levels in the second
      patient). Plain x-rays of the forearm revealed ossification of the interosseous
      membrane, which is characteristic of fluorosis. INTERVENTION: Both patients
      underwent decompressive laminectomy with removal of the OLF. The laminae and
      ossified yellow ligaments formed one mass of bone, which was removed with
      rongeurs and drills. After surgery, the first patient demonstrated improvement in
      motor power, whereas the second patient did not demonstrate any change in
      neurological status. CONCLUSION: Fluorosis should be entertained in the
      differential diagnosis of OLF, especially in patients from endemic areas. The
      magnetic resonance imaging appearance of the spine in such cases is
      characteristic. In properly selected cases of fluorotic myelopathy, surgery is
      indicated. However, the prognosis is guarded, and long-term follow-up of these
      patients is necessary given the nature of the underlying disease.

PMID- 15730590
TI  - Cavernous malformation of the trigeminal nerve manifesting with trigeminal
      neuralgia: case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe a patient with a cavernous malformation
      within the trigeminal nerve at the nerve root entry zone who presented with
      trigeminal neuralgia. CLINICAL PRESENTATION: A 52-year-old woman sought treatment
      after experiencing dizziness and lancinating left facial pain for almost a year.
      Neurological examination revealed diminished sensation in the distribution of the
      trigeminal nerve on the left. Magnetic resonance imaging demonstrated a minimally
      enhancing lesion affecting the trigeminal nerve. INTERVENTION: The patient
      underwent a retrosigmoid craniotomy. At the nerve root entry zone, the trigeminal
      nerve was edematous with hemosiderin staining. The lesion, which was resected
      with microsurgical technique, had the appearance of a cavernous malformation on
      gross and histological examination. The patient's pain improved significantly
      after resection. CONCLUSION: Cavernous malformations can afflict the trigeminal
      nerve and cause trigeminal neuralgia. Microsurgical excision can be performed
      safely and is associated with improvement in symptoms.

PMID- 15730591
TI  - An unusual cause of overdose after baclofen pump implantation: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intrathecal baclofen delivery for the treatment of
      spasticity has been used for almost 20 years with a great deal of success. A wide
      variety of complications and pitfalls have been described. This report details a
      novel complication involving inadvertent and initially unrecognized canalization
      of the subdural space with the spinal catheter, which ultimately resulted in an
      overdose. CLINICAL PRESENTATION: An intrathecal pump system was implanted in a 15
      year-old girl with spasticity. This initially resulted in a lack of therapeutic
      effect. The diagnostic workup ultimately led to contrast administration through
      the pump system, which precipitated a baclofen overdose when sequestered
      medication in the subdural compartment was released into the intrathecal space.
      INTERVENTION: The spinal catheter was subsequently revised, and the patient made
      a full recovery. CONCLUSION: The possibility of a subdural catheter should be
      included in the differential diagnosis in patients who experience a lack of drug
      effect after pump implantation, despite increases in dosage. Close monitoring is
      required because of the risk of spontaneous or induced overdose, which may occur
      when a communication develops between the subdural and intrathecal compartments.

PMID- 15730592
TI  - Cervical dumbbell intra-extradural hemangioblastoma: total removal through the
      lateral approach: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Extradural hemangioblastomas account for 8 to 12% of
      all spinal hemangioblastomas. Among them, intra-extradural forms with a dumbbell
      extension are extremely rare. We report a case of intra-extradural
      hemangioblastoma involving the C6 cervical nerve root. CLINICAL PRESENTATION: The
      patient was a 31-year-old woman presenting with signs of myelopathy and C6
      radiculopathy on the right side. A computed tomographic scan and magnetic
      resonance imaging demonstrated a dumbbell tumor that had developed through the C5
      C6 intervertebral foramen. Angiography revealed a well-circumscribed mass with
      feeders from the vertebral artery and the deep cervical artery. INTERVENTION: The
      tumor was totally removed through the lateral approach, with control of the
      vertebral artery and sacrifice of the C6 cervical nerve root. Limited bone
      drilling to enlarge the foramen permitted us to reach and resect the intradural
      component. Histopathological examination confirmed the diagnosis of
      hemangioblastoma. Follow-up was uneventful. CONCLUSION: This is the sixth
      reported case of a cervical dumbbell hemangioblastoma investigated by computed
      tomographic scanning and MRI but the first one resected via the lateral approach.
      The lateral approach seems appropriate for surgical resection because it provides
      primary control of the vascular feeders and access to the extradural and
      intradural components.

PMID- 15730593
TI  - Neuroendovascular interventions for intracranial posterior circulation disease
      via the transradial approach: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: To describe our experience with the transradial
      approach for posterior circulation neurointerventional procedures. To the best of
      our knowledge, this approach has not been described previously for intracranial
      neuroendovascular procedures. CLINICAL PRESENTATION: The clinical and imaging
      characteristics as well as periprocedural outcomes of patients treated for
      intracranial posterior circulation disease via the transradial approach were
      analyzed retrospectively. INTERVENTION: Between January 1 and October 21, 2003,
      four patients with posterior circulation disease (aneurysm, n = 1, and
      atherosclerotic stenosis, n = 3) were treated via the transradial approach
      because of tortuous brachiocephalic anatomy. Procedural success was 100%, and
      there were no procedural complications. No technical difficulties were
      encountered. CONCLUSION: The transradial approach is an alternative to the
      femoral approach for posterior circulation neuroendovascular intervention. This
      approach has several advantages over other approaches, and the vasculature can be
      less tortuous than that encountered during the femoral approach. These factors
      can result in increased device trackability and procedural ease.

PMID- 15730594
TI  - Repair of intractable cerebrospinal fluid rhinorrhea with mucosal flaps and
      recombinant human basic fibroblast growth factor: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Repair of a cerebrospinal fluid leak is not always
      easy, especially when a large fistula, with concomitant infection and injured
      mucosa, has developed from repeated transsphenoidal operations. We repaired such
      a sellar floor defect with mucosal flaps via the endonasal endoscopic approach
      and finally obliterated the fistula by promoting granulation-like tissue
      formation with recombinant human basic fibroblast growth factor (bFGF). CLINICAL
      PRESENTATION: A 27-year-old woman with intractable cerebrospinal fluid rhinorrhea
      was referred to our department after repeated operations for a relapsing Rathke's
      cleft cyst. Endonasal endoscopic examination revealed a large bone defect on the
      sellar floor through which previously packed fat and fascia were exposed to the
      nasal cavity. INTERVENTION: Mucosal flaps were harvested endoscopically from the
      nasal septum and the superior and middle turbinates. These pedicled flaps were
      transposed to the sellar defect. The flaps survived but did not cover the whole
      area, resulting in gaps between the flaps through which cerebrospinal fluid still
      leaked. Recombinant bFGF was repeatedly applied endoscopically to the mucosal
      flaps. The flaps turned into granulation-like tissue, and complete mucosal
      covering was finally achieved. CONCLUSION: bFGF has a wide range of biological
      effects, including stimulation of fibroblast growth and promotion of
      angiogenesis. It accelerates wound healing and is used clinically to treat dermal
      ulcers. The method presented here to treat an intractable fistula with mucosal
      flap and recombinant bFGF may suggest a new clinical application of bFGF. This
      possibility should be examined in a large number of patients in the future.

PMID- 15730595
TI  - Three-dimensional fast imaging employing steady-state acquisition magnetic
      resonance imaging for stereotactic radiosurgery of trigeminal neuralgia.
AB  - OBJECTIVE: The aim of this study was to demonstrate the use and applications of
      the three-dimensional fast imaging employing steady-state acquisition (3-D
      FIESTA) magnetic resonance imaging sequence in targeting and planning for
      stereotactic radiosurgery of trigeminal neuralgia. METHODS: A 3-D-FIESTA sequence
      for visualization of cranial nerves in the cranial base was added to the routine
      magnetic resonance imaging scan to enhance the treatment planning for trigeminal
      neuralgia. T1-weighted images, 1 mm thick, were directly compared with the FIESTA
      sequence for the exact visualization of the trigeminal entry zone and surrounding
      vasculature. The target accuracy was evaluated by image fusion of computed
      tomographic and magnetic resonance imaging scans. The anatomy visualized with the
      FIESTA sequence was validated by direct inspection of the gross anatomic
      specimens of the trigeminal complex. RESULTS: A total of 15 consecutive patients,
      10 women and 5 men, underwent radiosurgery for essential trigeminal neuralgia
      between April and July, 2003. The mean age of the patients was 65.2 years (range,
      24-83 yr). Nine patients had right-sided symptoms. Four patients had had previous
      surgery (two microvascular decompression, one percutaneous rhizotomy, and one
      radiofrequency thermocoagulation). The 3-D-FIESTA sequence successfully
      demonstrated the trigeminal complex (root entry zone, trigeminal ganglion,
      rootlets, and vasculature) in 14 patients (93.33%). The 3-D-FIESTA sequence also
      allowed visualization of the branches of the trigeminal nerve inside Meckel's
      cavity. This exact visualization correlated precisely with the anatomic
      specimens. In one patient (6.66%), it was not possible to demonstrate the related
      vasculature. However, the other structures were clearly visualized. CONCLUSION:
      The 3-D-FIESTA sequence is used in this study for demonstration of the exact
      anatomy of the trigeminal complex for the purpose of radiosurgical planning and
      treatment of trigeminal neuralgia. With such imaging techniques, radiosurgical
      targeting of specific trigeminal nerve branches may be feasible. It has not been
      possible previously to target individual branches of the trigeminal nerve.

PMID- 15730596
TI  - Oxygen delivery using self-inflating resuscitation bags.
AB  - OBJECTIVE: Oxygen-filled self-inflating resuscitators are used by some as a
      source of oxygen for spontaneously breathing patients. In this application, the
      bag is not compressed and oxygen is assumed to flow freely from the patient
      outlet through a mask positioned loosely over the patient's face. We tested 11
      resuscitators to determine the delivery of oxygen from the patient outlet using
      different inlet flows. DESIGN: Bench test. SETTING: A pediatric intensive care
      unit. INTERVENTIONS: Patient outlet flow was measured at inlet flows of 5, 10,
      and 15 L/min at two different orientations of the reservoir valve assembly
      (upright and inverted). MEASUREMENTS AND MAIN RESULTS: Patient outlet flow varied
      between resuscitators but was always less than the inlet flow and, in some cases,
      was as little as approximately 20% of the inlet flow. As the inlet flow rate was
      increased, the percentage of outlet flow that a patient received decreased,
      particularly in the upright position. At inlet flows of 5, 10, and 15 L/min,
      patient outlet flow ranged from 1.1 to 4.6 L/min, 1.6 to 5.1 L/min, and 2.0 to
      6.5 L/min, respectively. CONCLUSIONS: Self-inflating resuscitators deliver a
      significantly lower flow of oxygen than the provided inlet flow and should not be
      relied on to deliver a precise amount of flow of oxygen to spontaneously
      breathing patients.

PMID- 15730597
TI  - Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin
      precursors for the determination of bacterial sepsis in febrile neutropenic
      children.
AB  - OBJECTIVE: Children with cancer often develop febrile illnesses after cytotoxic
      chemotherapy. Determining which children have serious bacterial infections in
      this vulnerable period would be valuable. We evaluated the ability of a rapid and
      sensitive assay for the concentration of calcitonin precursors (CTpr) as a
      sensitive diagnostic marker for bacterial sepsis in febrile, neutropenic children
      and determined the utility of measuring cytokines to improve the predictive value
      of this approach. DESIGN: Prospective cohort study. SETTING: Academic children's
      hospital. PATIENTS: Fifty-six children (aged 5 months to 17 yrs) with a known
      malignancy who presented with fever and neutropenia. INTERVENTIONS: Serial blood
      samples were obtained (admission, 24 hrs, and 48 hrs), and concentrations of
      CTpr, interleukin-6, and interleukin-8 were determined. Demographic and
      laboratory data from the patients were collected from the medical record.
      MEASUREMENTS AND MAIN RESULTS: Sixteen (29%) of the children met the criteria for
      bacterial sepsis. Plasma levels of CTpr and interleukin-8, but not interleukin-6,
      were increased at all time points in children with sepsis compared with those
      without sepsis. CTpr at 24 and 48 hrs after admission were reliable markers for
      sepsis (area under the curve = 0.92 and 0.908, respectively). Logistic regression
      using CTpr at 24 hrs in addition to interleukin-8 at 48 hrs produced the best-fit
      models associated with sepsis. Using cutoff values of CTpr >500 pg/mL and
      interleukin-8 >20 pg/mL produced a screening test for sepsis with 94% sensitivity
      and 90% specificity. CONCLUSIONS: Our data show the utility of a rapid and
      sensitive assay for CTpr combined with interleukin-8 as a highly sensitive and
      specific diagnostic marker of bacterial sepsis in febrile, neutropenic children.
      The use of these markers as a clinical tool may allow for better prognostication
      for clinicians and may eventually lead to more targeted therapies for this
      heterogeneous population.

PMID- 15730598
TI  - The impact of pediatric intensive care unit volume on mortality: a hierarchical
      instrumental variable analysis.
AB  - OBJECTIVE: To evaluate the relation between annual pediatric intensive care unit
      (PICU) admission volume and mortality. DESIGN: Nonconcurrent cohort design.
      SETTING: Pediatric patients included in the most currently available research
      database from the Pediatric Intensive Care Unit Evaluations (PICUEs). PATIENTS: A
      total of 34,880 consecutive pediatric admissions to a contemporary volunteer
      sample of 15 U.S. PICUs. MEASUREMENTS AND MAIN RESULTS: We conducted an
      instrumental variable analysis and adjusted for similarities between patients
      admitted to different PICUs using mixed-effects, hierarchical techniques. Case
      mix and severity of illness was adjusted for using patient-level data and the
      Pediatric Risk of Mortality, version III (PRISM III). On average, admission to
      higher-volume PICUs was associated with lower severity-adjusted mortality (odds
      ratio = 0.68 per 100 patient increase in volume; 95% confidence interval: 0.52
      0.89) when volume was analyzed as a linear term; however, when PICU volume was
      analyzed as a quadratic term, we found the lowest severity-adjusted mortality
      rates among PICUs with annual admission volumes between 992 and 1,491.
      Furthermore, lower severity-adjusted mortality rates were primarily found among
      patients with less than a 10% PRISM III predicted risk of mortality. CONCLUSIONS:
      Although there is an association between lower severity-adjusted mortality among
      higher volume PICUs, our data suggest that best outcomes are among mid- to large
      sized PICUs. These data support minimum annual admission criteria for PICUs but
      raise the concern that PICUs with very high annual admission volumes may operate
      beyond an ideal capacity.

PMID- 15730599
TI  - Theophylline versus terbutaline in treating critically ill children with status
      asthmaticus: a prospective, randomized, controlled trial.
AB  - OBJECTIVE: To compare the efficacy of theophylline, terbutaline, or theophylline
      combined with terbutaline treatment in critically ill children with status
      asthmaticus who are already receiving continuous nebulized albuterol and
      intravenous corticosteroids. DESIGN: Randomized, prospective, controlled, double
      blind trial. SETTING: Pediatric intensive care unit of a tertiary-care children's
      medical center. PATIENTS: Forty critically ill children between the ages of 3 and
      15 yrs with impending respiratory failure secondary to status asthmaticus.
      INTERVENTIONS: All patients received intravenous methylprednisolone and
      continuous nebulized albuterol. The three study groups received theophylline plus
      placebo (group 1), terbutaline plus placebo (group 2), or theophylline and
      terbutaline together (group 3). MEASUREMENTS AND MAIN RESULTS: Differences in
      baseline characteristics, change in clinical asthma score over time, length of
      pediatric intensive care unit stay, and incidence of adverse events were
      determined. The three study groups were similar in age, gender, race, asthma
      severity, and treatment. There were no differences in clinical asthma score over
      time, length of pediatric intensive care unit stay, or incidence of adverse
      events between the three groups, with the exception of a higher incidence of
      nausea in children in group 3. The median hospital cost of medication and
      theophylline blood levels was significantly lower in group 1 compared with groups
      2 and 3 (280 US dollars vs. 3,908 US dollars vs. 4,045 US dollars, respectively,
      p < .0001). CONCLUSIONS: Theophylline, when added to continuous nebulized
      albuterol therapy and intravenous corticosteroids, is as effective as terbutaline
      in treating critically ill children with status asthmaticus. The addition of
      theophylline to baseline therapy is more cost-effective when compared with
      terbutaline alone or terbutaline and theophylline together. Theophylline should
      be considered for use early in the management of critically ill asthmatic
      children.

PMID- 15730600
TI  - Supplemental inhaled gases alter tidal volume delivery and measurement.
AB  - OBJECTIVE: Supplemental inspired nitrogen (N(2)) or carbon dioxide (CO(2)) is
      commonly used to balance pulmonary blood flow in patients with single-ventricle
      physiology. The objective of this study was to assess if supplemental inspired
      gas alters delivery or measurement of tidal volume (V(T)) by a ventilator.
      DESIGN: Prospective, experimental study. SETTING: Respiratory Care Laboratory,
      Cincinnati Children's Hospital. INTERVENTIONS: Using a test lung, expired V(T)
      measurements from Servo 300 ventilators were compared with actual delivered V(T)
      (true V(T)) at baseline and during supplemental N(2) or CO(2) administration to
      mimic clinical use in single-ventricle patients. At compliance settings
      simulating normal and compromised lung function, true V(T) was determined by the
      test lung and inline Pneumotach. True and measured V(T) were compared by repeated
      measures analysis of variance with significance defined as p < .05. MEASUREMENTS
      AND MAIN RESULTS: With normal lung compliance, supplemental gas administration
      increases both true and measured V(T), and expired V(T) measurements remain
      accurate. With poor lung compliance, supplemental gas flow disproportionately
      affects V(T) measurement. Poor lung compliance reduces true V(T) markedly (p <
      .001), causing a large discrepancy between true and measured V(T). Supplemental
      gas administration amplifies this discrepancy because the additional gas flow in
      the circuit erroneously augments expired V(T) measurements by the ventilator (p <
      .001). The discrepancy is greatest with higher-set V(T) and greater supplemental
      gas flow. CONCLUSIONS: The addition of supplemental inspired gas directly into
      the ventilator circuit can alter tidal volume delivery or measurement by a
      ventilator. The extent and magnitude of the alterations are determined by lung
      compliance. Variable effects of supplemental gas administration may confound
      ventilator management of patients with single-ventricle physiology.

PMID- 15730601
TI  - Thyroid function and ioduria in infants after cardiac surgery: comparison of
      patients with primary and delayed sternal closure.
AB  - OBJECTIVES: Thyroid hormone alterations after cardiac surgery may be aggravated
      by the use of iodine antiseptics. We evaluated thyroid function and ioduria in
      infants with delayed sternal closure (DSC) who are exposed to povidone-iodine for
      sternal wound protection and compared them with findings in infants after primary
      sternal closure. DESIGN: Prospective clinical study. SETTING: Pediatric cardiac
      intensive care unit. PATIENTS: Ninety-three infants after cardiac surgery using
      cardiopulmonary bypass, 60 of them with primary sternal closure and 33 of them
      with delayed sternal closure. MEASUREMENTS AND MAIN RESULTS: Thyroid hormones
      were studied in patients with primary sternal closure immediately after surgery,
      5 days and 19 days after surgery, in patients with DSC immediately after surgery,
      immediately after sternal closure, and 2 wks after sternal closure. Ioduria was
      evaluated on the first, third, and fifth postoperative days after cardiac surgery
      with primary sternal closure and immediately after DSC. In both groups of
      patients, low total triiodothyronine, total thyroxine, thyroxine-binding globulin
      levels, high reverse triiodothyronine levels, and normal free triiodothyronine,
      free thyroxine, and thyroid-stimulating hormone levels were recorded immediately
      after surgery. Concentrations of total triiodothyronine and thyroid-stimulating
      hormone were lower in the patients with DSC. Five days after primary sternal
      closure and 2 wks after DSC, all thyroid hormone levels were normal for age.
      Ioduria after DSC was higher than ioduria after primary sternal closure.
      CONCLUSIONS: Patients with DSC compared with patients with primary sternal
      closure display more profound thyroid suppression in the immediate postoperative
      period. The use of povidone-iodine adhesive drapes with single povidone-iodine
      mediastinal irrigation in patients with DSC is associated with significant iodine
      absorption but no significant thyroid dysfunction.

PMID- 15730603
TI  - Risk factors for extubation failure in mechanically ventilated pediatric
      patients.
AB  - OBJECTIVE: To describe the incidence of extubation failure and its associated
      risk factors among mechanically ventilated children. METHOD: Prospective cohort
      study. Children who were mechanically ventilated for longer than 12 hrs were
      followed up to 48 hrs after extubation. Cases of upper airway obstruction,
      accidental extubation, tracheostomy, or death before extubation were excluded.
      Extubation failure was defined as reintubation within 48 hrs after extubation.
      Student's t -test, Mann-Whitney, and chi-squared tests, odds ratio with 95%
      confidence interval, and multivariate analysis were used for data analysis.
      RESULTS: Extubation failure rate was 10.5% (13 of 124 patients). Variables
      associated with extubation failure were age between 1 and 3 mos (odds ratio [OR]
      = 5.68; 95% confidence interval [CI] = 1.58-20.42), mechanical ventilation >15
      days (OR = 6.36; 95% CI = 1.32-30.61), mean oxygenation index (OI) >5 (OR = 4.08;
      95% CI = 1.25-13.30), mean airway pressure 24 hrs before extubation lower than 5
      cm H(2)O (OR = 6.03; 95% CI = 1.48-24.60), continuous positive airway pressure
      (CPAP) (OR = 4.71; 95% CI = 1.34-16.58), dopamine and dobutamine use (OR = 3.71;
      95% CI = 1.08-12.78), intravenous sedation >10 days (OR = 6.60; 95% CI = 1.62
      26.90), tachypnea and subcostal retractions (relative risk [RR] = 3.68; 95% CI =
      1.14-11.93), and inspired fraction of oxygen (Fio(2)) > 0.4 after extubation (RR
      = 3.63; 95% CI = 1.21-10.88). After multiple logistic regression analysis, age
      between 1 and 3 mos, mean OI > 5, CPAP and mechanical ventilation >15 days
      remained associated with extubation failure. CONCLUSION: Extubation failure was
      more frequent among young infants who received prolonged ventilatory support and
      intravenous sedation, used CPAP, had impaired lung oxygenation, and required
      inotropic therapy.

PMID- 15730602
TI  - Cost-effectiveness of exogenous surfactant therapy in pediatric patients with
      acute hypoxemic respiratory failure.
AB  - OBJECTIVE: To determine whether the use of exogenous surfactant (Infasurf) in
      pediatric acute hypoxemic respiratory failure is cost-effective. DESIGN:
      Deterministic cost-effectiveness analysis based on a Markov model. The model was
      calibrated using outcomes and resource utilization observed in a multiple
      centered, prospective, randomized, controlled unblinded trial of Infasurf in
      pediatric acute hypoxemic respiratory failure. Costs were short-run direct costs
      estimated from the perspective of the hospital as provider. Primary outcomes were
      expected costs, expected survival rates, and incremental cost per life saved.
      SETTING: Patients in the trial were treated in one of eight pediatric intensive
      care units of tertiary medical centers. PATIENTS: Forty-two children with acute
      hypoxemic respiratory failure who were randomized to receive either standard
      therapy or exogenous surfactant in addition to standard therapy. MEASUREMENTS AND
      MAIN RESULTS: Our baseline analysis suggests that for a 10-kg child, the Infasurf
      strategy is both less costly (62,922 US dollars vs. 74,006 US dollars) and more
      effective (survival: 90.3% vs. 85.1%) and therefore dominates standard treatment.
      Cost savings were realized in the model because patients in the surfactant group
      were more likely to leave the pediatric intensive care unit sooner. The Infasurf
      strategy continues to dominate for children up to 60 kg. At 70 kg, the cost to
      save an additional life using the Infasurf strategy is 79,805 US dollars, which
      is still cost-effective if the provider is willing to make this tradeoff.
      CONCLUSIONS: For the majority of pediatric patients with acute hypoxemic
      respiratory failure, exogenous surfactant is cost-effective. If the use of this
      medication becomes standard care, a greater variety of packaging sizes could lead
      to decreased acquisition costs and increase the number of patients for whom this
      treatment is cost-effective.

PMID- 15730604
TI  - Does gender affect neonatal hyperbilirubinemia in low-birth-weight infants?
AB  - BACKGROUND: Neonatal mortality and morbidity are gender-biased in low-birth
      weight (LBW) infants. The male disadvantage theory has been suggested to be
      responsible for these maturational differences. OBJECTIVE: To examine the impact
      of gender on neonatal hyperbilirubinemia. DESIGN/METHODS: A retrospective
      observational study. Data on all LBW infants admitted to George Washington
      University neonatal intensive care unit and surviving for >48 hrs from January
      1992 to March 2003 were analyzed. Males and females were compared for gestational
      age, birth weight, race, Apgar scores at 1 and 5 mins, peak bilirubin levels,
      sepsis, and intraventricular hemorrhage (IVH). Significant differences were
      entered in a regression model to detect the influence of gender on bilirubin
      (Bili). Analysis was repeated after stratification of infants into: group A,
      <1000 g; group B, 1000-1499 g; and group C, 1500-2499 g. RESULTS: A total of 840
      infants were included in this study. When comparing males (n = 407) with females
      (n = 433), significant differences were detected in birth weight (1,539 +/- 541
      vs. 1,428 +/- 549 g; p = .003), IVH (14.2% vs. 9%; p = .025), and Bili (10.1 +/-
      3.0 vs. 9.2 +/- 2.8 mg%; p < .001). No differences were detected in gestational
      age, sepsis, or Apgar 1 and 5. Difference in Bili for the entire group remained
      significant in the regression model (regression coefficient [RC] = 0.79 +/- 0.22;
      p < .001). In subgroup analyses: group A Bili (8.4 +/- 2.3 vs. 8.0 +/- 2.0; p =
      .14) and group B Bili (9.0 +/- 2.1 vs. 9.2 +/- 2.2; p = .51) did not differ in
      bivariate or multivariate analyses. In group C, Bili was (11.3 +/- 3.1 vs. 10.1
      +/- 3.3; p < .001) and remained the only significant difference in the regression
      model (RC = 1.19 +/- 0.37; p = .001). CONCLUSIONS: Bili in LBW infants is
      significantly higher in males when compared with females. After stratification to
      birth weight subgroups, significance is retained in the 1500- to 2499-g group
      after logistic regression analysis. Bili levels in infants <1500 g are influenced
      more significantly by factors other than gender, such as sepsis and IVH.

PMID- 15730605
TI  - Intratracheal pressure: a more accurate reflection of pulmonary airway pressure
      in pediatric patients with respiratory failure.
AB  - OBJECTIVES: Peak inflation pressure (PIP) on many ventilators (P(vent)), measured
      distal to the exhalation limb or Y-piece of the breathing circuit, is assumed as
      the pressure applied to the airways and lungs. However, in vitro studies show
      P(vent) data are spurious. There are no studies evaluating the accuracy of
      P(vent) data for pediatric patients with acute respiratory failure. We
      hypothesized that intratracheal airway pressure (P(T)) is more accurate than
      P(vent) and that by using P(vent), abnormally increased imposed resistive work of
      breathing (WOBi) may go undetected. DESIGN: Prospective and descriptive study.
      SETTING: A pediatric intensive care unit at a university hospital. PATIENTS:
      Twenty-one pediatric patients with respiratory failure requiring mechanical
      ventilation. INTERVENTIONS: All patients were intubated with a commercially
      available endotracheal tube (ETT) with a pressure measuring the lumen opening at
      the distal end used for measuring P(T). Pressure/flow sensors positioned between
      the ETT and Y-piece measured tidal volume (V(T)) and flow rate. P(vent) data were
      recorded as displayed on the ventilator. WOBi was measured by integrating P(T)
      and V(T) data. RESULTS: PIP at P(vent) and P(T) were 26 +/- 8 cm H(2)O and 19 +/-
      7 cm H(2)O, respectively (p < .05). P(T) measurements averaged 27% less than
      P(vent). The relationship between P(vent)-P(T) (pressure drop across the
      breathing circuit and ETT) and flow rate during spontaneous inhalation was highly
      correlated (r = .80, p < .002), indicating the greater the flow rate, the greater
      the pressure drop and WOBi. WOBi, ranging from 0.04-1.5 J/L, was measured in 52%
      of the patients. CONCLUSIONS: P(vent) significantly overestimates PIP. Moreover,
      P(vent) data does not allow for recognition of increased WOBi for many patients.
      Clinicians need to be aware of the limitations of P(vent) data and consider using
      ETTs that allow measurement of P(T), a more accurate reflection of pulmonary
      airway pressure.

PMID- 15730606
TI  - Failure of nasogastric omeprazole suspension in pediatric intensive care
      patients.
AB  - OBJECTIVES: To determine the efficacy of nasogastric administration of omeprazole
      suspension in raising the gastric pH >4 in critically ill pediatric patients and
      to determine the most appropriate dosing regimen for this indication. DESIGN:
      Open-label pharmacodynamic study. SETTING: Twenty-six bed tertiary-care pediatric
      intensive care unit. PATIENTS: Mechanically ventilated children aged 1-18 yrs
      with an additional risk factor for stress ulcer formation. INTERVENTIONS:
      Continuous gastric pH monitoring was performed during administration and dose
      titration of omeprazole suspension to achieve the goal of gastric pH >4 for
      greater than 75% of the dosing interval. MEASUREMENTS AND MAIN RESULTS: Data were
      collected from 18 patients. Subjects were categorized based on the pharmacologic
      response to nasogastric administration of 1 mg/kg omeprazole suspension (maximum
      20 mg) as rapid (n = 9), late (n = 5), and nonresponders (n = 4). Rapid
      responders required 0.72 mg/kg per day omeprazole suspension to achieve adequate
      gastric pH elevation for stress ulcer prophylaxis. Late responders required 1.58
      mg/kg per day. Nonresponders did not achieve adequate elevation of gastric pH for
      stress ulcer prophylaxis. CONCLUSIONS: Nasogastric administration of omeprazole
      suspension has variable efficacy in critically ill pediatric patients. Half of
      the studied subjects either required significant dose titrations to achieve
      gastric acid suppression or did not respond to nasogastric administration of
      omeprazole suspension.

PMID- 15730607
TI  - Hyperoxia-induced changes in human airway epithelial cells: the protective effect
      of perflubron.
AB  - OBJECTIVE: To determine the protective effect of perflubron (PFB), a type of
      perfluorochemical liquid, in hyperoxia-induced cellular injury in the human
      airway epithelial cells. DESIGN: A controlled, in vitro laboratory study.
      SETTING: Tertiary-care children's hospital. SUBJECTS: Human airway epithelial
      cells. INTERVENTIONS: Human airway epithelial cells, Calu-3 cells, grown on
      polycarbonate porous filters at an air-liquid interface culture were exposed to
      normoxic (Fico(2) = 5%, balance air) or hyperoxic (Fio(2) = 95%, balance CO(2))
      conditions. Hyperoxia-induced cellular changes were monitored by measuring
      transepithelial resistance (TER) of monolayers, histology of cells, total
      protein, and interleukin-8 (IL-8) secretion in apical surface fluid (ASF)
      washings. Under hyperoxic conditions, the protective effect of PFB was assessed
      by directly adding PFB liquid to the apical surface of monolayers. MEASUREMENTS
      AND MAIN RESULTS: During hyperoxic gas-liquid interface culture, Calu-3
      monolayers exhibited a loss of cellular integrity morphologically, decreased
      protein concentration, and IL-8 level in ASF washings. During hyperoxic PFB
      liquid interface culture, there was an overall increase in TER value of
      monolayers, improved histology, decreased total protein secretion in ASF
      washings, and unaltered IL-8 secretion. Cytomorphologic observations of PFB
      treated Calu-3 cells indicated the presence of varying numbers of differently
      sized intracellular vacuoles during both normoxic and hyperoxic conditions.
      CONCLUSIONS: We conclude that the air-liquid interface culture of Calu-3 may be
      helpful in understanding mechanisms of lung injuries caused in clinical practice,
      and PFB protects against hyperoxia-induced airway epithelial cell injury by
      promoting cellular integrity as well as cytologic modifications. PFB-liquid
      interface culture of Calu-3 may be a useful in vitro model for studying the
      cytoprotective role of liquid ventilation.

PMID- 15730608
TI  - The effects of milrinone on hemodynamics in an experimental septic shock model.
AB  - OBJECTIVE: To investigate the specific hemodynamic effects of the
      phosphodiesterase inhibitor milrinone in a rabbit model of septic shock in the
      absence of any other treatment. DESIGN: A prospective, controlled, interventional
      study. Animal Model: Fourteen sedated New Zealand rabbits. SETTING: Research
      laboratory of a health sciences university. INTERVENTIONS: Rabbits were
      anesthetized and vascular catheters inserted in femoral artery and jugular vein.
      After a stabilization period and the recording of baseline measurements (H0), all
      animals received a 10-mL infusion of Pseudomonas aeruginosa. Two hours later
      (H2rabbits were randomly assigned to receive 5% dextrose (control group) or
      milrinone (milrinone group). MEASUREMENTS AND MAIN RESULTS: Mean arterial blood
      pressure (MAP) was monitored continuously, and a cardiac index (CI) was
      determined every 30 mins by a transpulmonary thermodilution technique using an
      integrated monitoring device (PICCO). No differences were detected between the
      two groups after stabilization (H0) or before the treatment (H2) for either CI
      (mL/min(-1)/kg(-1)) or MAP (mm Hg). CI decreased progressively in the control
      group during the following 4 hrs, but not in the treated group (at H6: 122 +/- 4
      vs. 207 +/- 16 mL/min(-1)/kg(-1); p < .05). No drop of MAP occurred after
      milrinone infusion. A comparison of the treated and control group reveals that
      milrinone improved tissue perfusion as evidenced by measurements of central
      venous saturation (at H4: 0.59 +/- 0.05 vs. 0.71 +/- 0.03, p = .04), lactacidemia
      (at H6: 10.3 +/- 2.4 vs. 3.9 +/- 0.9 mmol/L, p = .03), creatinemia (at H6: 95 +/-
      11 vs. 60 +/- 5 micromol/L, p = .02) and survival (at H6: 5 vs. 7, not
      significant). CONCLUSION: Milrinone improves cardiac output and tissue perfusion
      in a rabbit model involving severe septic shock.

PMID- 15730609
TI  - Extracorporeal membrane oxygenation after stem cell transplant: clinical decision
      making in the absence of evidence.
AB  - OBJECTIVE: To discuss the ethical dilemmas that arise in considering innovative
      therapies for critically ill children when there is little data to support their
      use. DESIGN: Case report of a 13-yr-old patient after autologous peripheral blood
      stem cell transplant for stage III neuroblastoma with sepsis and hemodynamic
      instability who survived to discharge after a 6-day course of extracorporeal
      membrane oxygenation (ECMO) support. The case serves as a source of discussion of
      the following: the use of available data in deciding to proceed with an unproved
      therapy, the approach to conversations to obtain informed consent, and the need
      for institutional oversight and hypothesis-driven data collection to advance
      pediatric critical care. SETTING: Pediatric intensive care unit at a university
      hospital. PATIENT: One adolescent with stage III neuroblastoma. RESULTS: Despite
      a lack of data to support the use of ECMO in a neutropenic oncology patient after
      autologous peripheral blood stem cell transplant, our patient had clinical
      features that suggested he was a reasonable ECMO candidate. His family gave
      informed consent to use ECMO and he survived. It is ethical to consider and use
      innovative therapies when patient characteristics are suggestive that the therapy
      may be successful even in the absence of evidence. This requires physicians'
      attention to the best interest of the patient and should occur in the setting of
      informed consent and rigorous data collection. CONCLUSIONS: The boundaries among
      standard therapy, innovative therapy, and research can be quite fluid. This case
      illustrates the ethical imperative to consider therapies that may be appropriate
      for a critically ill child even without evidence predictive of success, to have
      entry criteria and treatment protocols for such therapies, and to collect data
      from such experiences to advance the standard of care.

PMID- 15730610
TI  - Heliox administration in the pediatric intensive care unit: an evidence-based
      review.
AB  - OBJECTIVE: To provide a comprehensive, evidence-based review of helium-oxygen gas
      mixtures (heliox) in the management of pediatric respiratory diseases. DATA
      SOURCE: A thorough, computerized bibliographic search of the preclinical and
      clinical literature regarding the properties of helium and its application in
      pediatric respiratory disease states. DATA SYNTHESIS: After an overview of the
      potential benefits and technical aspects of helium-oxygen gas mixtures, the role
      of heliox is addressed for asthma, aerosolized medication delivery, upper airway
      obstruction, postextubation stridor, croup, bronchiolitis, and high-frequency
      ventilation. The available data are objectively classified based on the value of
      the therapy or intervention as determined by the study design from which the data
      are obtained. CONCLUSIONS: Heliox administration is most effective during
      conditions involving density-dependent increases in airway resistance, especially
      when used early in an acute disease process. Any beneficial effect of heliox
      should become evident in a relatively short period of time. The medical
      literature supports the use of heliox to relieve respiratory distress, decrease
      the work of breathing, and improve gas exchange. No adverse effects of heliox
      have been reported. However, heliox must be administered with vigilance and
      continuous monitoring to avoid technical complications.

PMID- 15730611
TI  - Heartbeat assessment in infants: a comparison of four clinical methods.
AB  - OBJECTIVE: To compare the performance of four clinical methods (apex ear
      auscultation; brachial, carotid, and femoral pulse palpation) for detecting and
      counting heart beat in infants. DESIGN: Cross-sectional, repeated-measures study
      design. Prospective data collection. SETTING: A postanesthesia care unit of a
      pediatric teaching hospital in Italy. PATIENTS: Fifty-six normotensive sedated
      infants, aged 1-12 mos, were evaluated by 14 pediatric basic life support (PBLS)
      qualified health professionals. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The proportion of successful heartbeat detections ranged from 60% with
      carotid pulse palpation to 98% with apex auscultation. Among successful
      detections, apex auscultation proved to be the most rapid way to detect heart
      rate (median, 4 secs) and the most accurate with a median discrepancy of 8
      beats/min (vs. 12 with the other methods) from the electrocardiographic results.
      Differences between apex auscultation and pulse palpation were statistically
      significant (p < .0001). In contrast, no significant differences were found among
      the three methods of pulse checking. CONCLUSIONS: Apex listening is the most
      successful, rapid, and accurate method to detect and count the heartbeat by PBLS
      certified professionals in normotensive infants without instruments. Pulse
      checking remains important for assessing the effectiveness of circulation.
      Palpating the brachial, carotid, or femoral pulse is equally effective.

PMID- 15730612
TI  - Heparin-induced thrombocytopenia in the pediatric intensive care unit population.
AB  - OBJECTIVES: To report the occurrence of heparin-induced thrombocytopenia (HIT),
      discuss its pathophysiology, and outline an approach to management in the
      pediatric intensive care unit (ICU) patient. DESIGN: Retrospective case reports.
      SETTING: Pediatric ICU in a tertiary-care center. PATIENTS AND RESULTS: Two
      pediatric ICU patients (2 and 6 mos of age) who developed HIT in the pediatric
      ICU. One was receiving heparin as a flush solution through a central line and the
      other had full heparinization during cardiopulmonary bypass. Both had received
      heparin during their neonatal course and developed thrombocytopenia; however, HIT
      was not considered as a possible diagnosis. HIT was diagnosed using a heparin
      induced platelet aggregation study. The thrombocytopenia resolved with the
      cessation of heparin administration. One of the patients developed a deep vein
      thrombosis around a femoral venous catheter. CONCLUSION: Although well described
      in the adult literature, there have been a limited number of reports of HIT in
      pediatric-aged patients. Given its potential for morbidity, HIT should be
      considered in the differential diagnosis of thrombocytopenia in the pediatric ICU
      patient.

PMID- 15730613
TI  - Hyperosmolar solutions in continuous renal replacement therapy for hyperosmolar
      acute renal failure: a preliminary report.
AB  - OBJECTIVE: To demonstrate the efficacy of hyperosmolar dialysis and prefilter
      replacement fluid solutions for continuous renal replacement therapies in the
      correction of hyperosmolar disorders in acute renal failure. DATA SOURCE: An
      Institutional Review Board-approved pediatric acute renal failure database at the
      University of Michigan C. S. Mott Children's Hospital. STUDY SELECTION: Three
      patients were identified meeting the inclusion criteria. The mean serum sodium
      concentration and plasma osmolality were 158 mmol/L and 357 mOsm/kg,
      respectively, at the time of initiation of renal replacement therapy. The sodium
      and/or dextrose concentrations of the dialysate or replacement fluids initially
      were increased and subsequently decreased to affect the solutions' calculated
      osmolalities in an effort to control the rate of decline of the patients'
      measured plasma osmolalities. DATA EXTRACTION: The case patients' serum sodium
      concentrations and plasma osmolalities were measured. Additionally, the sodium
      and dextrose concentrations of the dialysate or replacement fluid were recorded
      and the solutions' osmolalities calculated. DATA SYNTHESIS: The three patients
      experienced a mean rate of reduction of their serum sodium concentration and
      plasma osmolality of 0.5 mmol/L/hr and 1.6 mOsm/kg/hr, respectively. CONCLUSIONS:
      Hyperosmolar dialysis or prefilter replacement fluid solutions can affect a slow
      decline in both the serum sodium and plasma osmolality in cases of hyperosmolar
      acute renal failure.

PMID- 15730614
TI  - Oxygen delivery during resuscitation with self-inflating bags: do not forget a
      very simple but important recommendation.

PMID- 15730615
TI  - [Evaluation of surgical protocols for gastric cancer].

PMID- 15730616
TI  - [Elevated expression level of wild-type survivin in gastric cancer promotes in
      vitro docetaxel-resistance].
AB  - OBJECTIVE: To study the expression of three survivin splicing variants in gastric
      cancer and to evaluate the significant correlation between survivin variants'
      expression and chemoresistance in gastric cancer. METHODS: Real time quantitative
      RT-PCR was used to analyze the mRNA expression of survivin variants in 39 gastric
      tumor specimens resected during operation. The clinical resistance to anticancer
      agents [CDDP, MMC, 5-Fu, docetaxel (Taxotere TXT), and GEM] was analyzed by
      histoculture drug-response assay (HDRA). RESULTS: Among the 39 tumor samples,
      survivin expression was detected in all tumor samples (39/39); 79.5% (31/39) of
      the samples demonstrated survivin-2B expression and 66.7% (26/39) of the samples
      had survivin-Delta Ex3 expression. HDRA showed that the in vitro efficacy rates
      of CDDP, MMC, 5Fu, TXT, and GEM were 36.8% (14/38), 31.2% (10/32), 23.1% (9/39),
      20.5% (8/39), and 12.5% (4/32) respectively, equivalent to the previous HDRA
      studies and historical clinical studies in gastric cancer patients. The
      expression rate of wild-type survivin was significantly higher in the group of
      chemoresistance to TXT than in the group sensitive to docetaxel (P = 0.021).
      CONCLUSION: Elevated expression level of wild-type survivin promotes docetaxel
      resistance in patients with gastric cancer.

PMID- 15730617
TI  - [Constitutive activation and clinical significance of Stat3 in human gastric
      cancer tissues and cell lines].
AB  - OBJECTIVE: To investigate the activation of signal transducers and activators of
      transcription 3 (Stat3) in different types of gastric cancer cell lines and
      tissues and evaluate the relationship with their clinicopathological parameters.
      METHODS: Western blotting and electrophoretic mobility shift assay (EMSA) were
      used to detected the expression of Stat3 protein and Stat3 DNA-binding activity
      in normal human gastric epithelial cell line 3T3 and five gastric cancer cell
      lines with different differentiation: MKN28, SGC7901, MKN45, AGS and NCI-SNU-1,
      respectively. The localization of phospho-Stat3 was determined by
      immunocytochemistry. The expressive intensity of phospho-Stat3 protein in 50
      cases of gastric cancer tissues and adjacent normal mucosa were measured by
      immunohistochemistry. RESULTS: Compared with normal gastric epithelial cell line
      3T3, elevated activities of Stat3 were found in five different human gastric
      cancer cell lines. The Stat3 DNA-binding activity in moderately and poorly
      differentiated stomach adenocarcinoma cell lines (SGC7901, MKN45 and AGS) was
      higher than that of other cell lines (MKN28 and NCI-SNU-1). Phospho-Stat3 was
      detected primarily in the nuclei of AGS cells. The expressive intensity of
      phospho-Stat3 protein was significantly increased in gastric cancer tissues as
      compared with the adjacent normal gastric mucosa, especially in moderately and
      poorly differentiated cancers (both P < 0.05). The expressive intensity of
      phospho-Stat3 protein in stage II and stage III tumors was higher than that in
      stage I tumors (P < 0.05). No statistic difference of phospho-Stat3 expression
      was found between stage IV and stage I tumors (P > 0.05). The expression of
      phospho-Stat3 was closely correlated with the differentiation of gastric cancer.
      CONCLUSION: Elevated activity of Stat3 can be found in different types of human
      gastric cancer cell lines and gastric cancer. JAK/STAT signal transduction
      pathway may play an important role in the development of human gastric cancer.

PMID- 15730618
TI  - [Effect of injecting activated carbon ultramicroparticles around the gastric
      tumor on staining lymph node].
AB  - OBJECTIVE: To observe the effect of injecting activated carbon
      ultramicroparticles around the gastric tumor before or during operation on
      staining lymph nodes and guiding the lymphadenectomy of gastric cancer. METHODS:
      Forty-three cases of gastric cancer received activated carbon (AC)
      ultramicroparticles around the tumor by submucosal endoscopic injection 1
      approximately 6 days before the operation and/or intraoperative subserosal
      injection (AC group), whereas 82 cases of gastric cancer without the injection
      were used as control group. The number of dissected lymph nodes, number of black
      stained lymph nodes and its relation to the injection time, metastasis of lymph
      nodes, and the side effect of the procedure were analyzed. RESULTS: The average
      numbers of resected lymph nodes were 34 +/- 13 in the AC group, significantly
      higher than that in the control group (16 +/- 9, P < 0.05). The dissected N(2)
      lymph nodes in the AC group was 25 +/- 9, significantly higher than that in the
      control group (8 +/- 4, P < 0.05). The total ratio of black-stained lymph node
      was 60.3% in general, 71.3% for the N1 lymph nodes and 56.3% for the N(2) lymph
      nodes in the AC group. Satisfactory effect of black staining of lymph nodes could
      be seen 2 days after local gastric tissue injection of activated carbon
      ultramicroparticles. The metastasis rate was 67.4% in the AC group, not
      significantly different from that in the control group (63.4%, P > 0.05). In the
      patients of AC group the metastasis rate of black-stained lymph node was 26.8%,
      significantly higher than that of the unstained lymph nodes (3.3%) and higher
      than that of the control group (18.4%). No serious side effect happened after the
      activated carbon ultramicroparticles injection in local gastric tissue.
      CONCLUSION: Local injection of activated carbon ultramicroparticles around the
      tumor is an effective, easy and safe procedure to guide gastric cancer
      lymphadenectomy.

PMID- 15730619
TI  - [Detection of HBcAg-specific cytotoxic lymphocytes and their association with
      clinical status in patients with hepatitis B].
AB  - OBJECTIVE: To investigate the difference of host immune response specific to
      hepatitis B virus (HBV) infections between acute self-limited and chronic
      persistent hepatitis by quantitative analysis of HLA-A * 2402-restricted HBcAg
      specific cytotoxic T lymphocyte cells (CTL) cells. METHODS: The frequency of HBV
      specific CTL cells in the peripheral blood mononuclear cells (PBMCs) from 20
      patients infected with HBV were quantified by ELISPOT assays and flow cytometry
      using one HLA-A * 2402-HBV, 7 with acute HB and 13 with chronic HB, peptide
      tetrameric complex. RESULTS: High frequencies of circulating HBcAg-specific CTL
      cells were detected in most individuals with acute HBV infection while the number
      of these cells was significantly reduced at the convalescent stage. HBcAg
      specific CTL cells were not detected in the PBMC from individuals with chronic
      HBV infection except for one patient with an acute infection exacerbation.
      CONCLUSION: HBcAg-specific CTL cells may play a crucial role in complete
      clearance of HBV from patients with acute HBV hepatitis.

PMID- 15730620
TI  - [Treatment of severe systemic autoimmune diseases with autologous peripheral
      blood stem cell transplantation].
AB  - OBJECTIVE: To investigate the feasibility, efficacy and safety of high dose
      immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell
      transplantation (PBSCT) with CD(34)(+) cell selection in patients with refractory
      and severe autoimmune diseases. METHODS: Twenty-one patients with SLE, RA, pSS,
      SSc or MCTD were enrolled in the study from 1999. Autologous haemopoietic stem
      cells were mobilized with CTX 3 approximately 4 g/m(2) and granulocyte colony
      stimulating factor (G-CSF). CD(34)(+) cells were selected by CliniMACS. After
      conditioning with CTX (200 mg/kg) and pig antithymocyte globulin (ATG, 90 mg/kg)
      or CTX (150 mg/kg) and total body irradiation (TBI, 4 approximately 6 Gy), the
      enriched CD(34)(+) cells were reinfused. RESULTS: All patients completed the
      mobilization and leukapheresis procedures successfully, and proceeded to receive
      conditioning and transplantation. Two patients died of complication related to
      transplantation, one is CMV infection, the other is severe pneumonia during the
      course of granulocyte deficiency. A MCTD patient completed the stem cell
      mobilization and died of severe pulmonary hypertension and heart failure before
      CD(34)(+) cells reinfusing. Two SLE patients relapsed in 26, 37 months
      respectively and a RA patient relapsed in 15 months after transplantation. Other
      patients got improved, with SLE-DAI score decreasing from 17 to 4 score and
      proteinuria decreasing from 6.7 g to 2.3 g in SLE patients; DAS28 score from 7.9
      to 2.1 in RA patient; Symptom improved and lab results recovered in SS.
      CONCLUSION: High dose immunosuppressive therapy followed by autologous peripheral
      blood stem cell transplantation with CD(34)(+) cell selection is feasible and
      relative safe. Patients remain free from disease active and improved
      continuously. Some patients could relapse after transplantation. Long-term effect
      need to be further observed.

PMID- 15730621
TI  - [Clinical characteristics of propylthiouracil (PTU) induced antineutrophil
      cytoplasmic antibodies positive cases; analysis of a case of PTU-induced ANCA
      positive patients with hyperthyroidism].
AB  - OBJECTIVE: To study the clinical characteristics of propylthiouracil (PTU)
      induced antineutrophil cytoplasmic antibodies (ANCA) positive cases and increase
      the awareness of PTU induced ANCA positive vasculitis (APV). METHODS: The
      clinical data of nine cases with positive ANCA induced by PTU in Peking Union
      hospital since 2000 were analyzed and literature review was conducted. RESULTS:
      (1) Nine patients with hyperthyroidism, at a mean age of 33.1 (16 approximately
      51), who were treated with PTU for a mean period of 32.4 months (3 approximately
      84); (2) Sera from nine cases were ANCA positive, and autoantibodies from six
      tested cases could recognize not only MPO, but also PR3, HLE, BPI and LF; (3) Six
      cases with high titer perinuclear ANGA (pANCA) (> or = 1:1280) were diagnosed APV
      and all had renal involvement (five confirmed by renal biopsies), three cases
      with low titer pANCA (< or = 1:320) had little clinical manifestations of
      vasculitis; (4) Eight patients stopped taking PTU when positive ANCA were noted.
      One case with APV got remission after stopping PTU, the other three APV were
      treated with glucocorticosteroid and immunosuppressive agents at meanwhile. Only
      one patient kept taking PTU for eighteen months without an increased titer of
      ANCA. CONCLUSION: PTU could induce production of ANCA. High titer of ANCA might
      suggest existence of APV and the titer would be associated with status of APV.
      Early withdrawal of PTU and administration of glucocorticosteroid and
      immunosuppressive agents based on renal pathology will greatly improve the
      prognosis.

PMID- 15730622
TI  - [Diagnosis and therapy of intracavernosal cavernous hemangioma].
AB  - OBJECTIVE: To study the diagnosis and therapy of intracavernosal cavernous
      hemangioma. METHODS: The clinical data, including pathology, epidemiology,
      medical imaging, operation procedure, and post-operational complication, of 43
      intracavernosal cavernous hemangioma patients undergoing operations in Tiantan
      Hospital 1996 to 2003 were analyzed. Frontotemporal craniotomy, frontal
      craniotomy, and combined fronto-temporal preauricular subtemporal approach were
      used for the 43 patients. RESULTS: The male/female ratio of these cases was
      1:2.58. The average age of onset was 44.28 (11 approximately 67). The initial
      symptoms included headache, diminution of vision, paralysis of occulomotor nerve,
      ambiopia, facial pain or numbness epilepsy, etc. Although showing no specific
      typical feature, MRI still helped in diagnosis. The tumor was totally removed in
      22 cases, subtotally removed in 11 cases, and partially removed in 10 cases. The
      main post-operational complications included oculomotor nerve paralysis (16
      cases), abducent nerve paralysis (10 cases), and facial nerve paralysis (3
      cases). No postoperative death occurred. CONCLUSION: Operation is still the best
      choice for intracavernosal cavernous hemangioma patients.

PMID- 15730626
TI  - [Protective effects of bicyclol on liver fibrosis induced by carbon
      tetrachloride].
AB  - OBJECTIVE: To study the protective effects and related mechanism of bicyclol on
      liver fibrosis induced by carbon tetrachloride (CCl(4)). METHODS: Forty male
      Wistar rats were injected subcutaneously with 25% CCl(4) twice a week for 3
      months. Since the 7th week the rats were divided into 4 groups of 10 rats: normal
      control group, CCl(4) model group, bicyclol 100 mg/kg group (perfused of bicyclol
      into stomach 100 mg/kg qd for 45 days), and bicyclol 200 mg/kg group (perfused of
      bicyclol into stomach 200 mg/kg qd for 45 days). Twenty-four hours after the last
      administration the rats were killed. The serum was isolated to measure the levels
      of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin
      (TB), albumin/globulin (A/G), total protein (TP), hyaluronic acid (HA), and pro
      collagen peptide III (PIIIP). Serum TNF alpha content was examined by ELISA
      assay, and liver TGF beta 1 level was determined by immunohistologic assay. The
      pathology of liver was examined. Twenty-eight mice were divided into 4 groups of
      7 mice: normal control group, subacute group, 100 mg bicyclol group (perfused of
      bicyclol into stomach 50 mg/kg bid), and bicyclol 200 mg/kg group (perfused of
      bicyclol into stomach, 100 mg/kg bid), and 200 mg bicyclol group. Carbon
      tetrachloride was injected subcutaneously to the mice in the latter 3 groups
      every 3 days for 1 month. Twenty-four hours after the last administration the
      mice were killed and the serum was isolated to measure the levels of ALT, AST,
      TP, and albumin. Mitochondria were extracted from the livers of the experimental
      animals to measure the amount of protein. Mitochondrial glutathione (GSH) and
      malondialdehyde (MDA) contents were measured. The MDA and GSH contents in the
      control group were regarded as 100%, and the percentages of MDA and GSH in other
      groups were calculated. The fluidity of mitochondrial membrane and swelling
      degree of mitochondria were measured. Imunohistochemistry was used to detect the
      liver TGF beta 1. Nuclear NF kappa B DNA binding activity was investigated by
      electrophoretic mobility shift assay. RESULTS: Three months after the
      administration of carbon tetrachloride the serum ALT, AST, TB, HA, and PIIIP
      levels of the CCl(4) model group increased by 24, 10, 8, 28, and 4 times and the
      levels of albumin and A/G decreased significantly in comparison with those of the
      normal control group. However, the serum ALT, AST, TB, HA, and PIIIP levels in
      the 2 bicyclol groups were significantly lower than those in the model group. The
      pathological changes in the liver of the 2 bicyclol groups were significantly
      lighter than those in the model group. The serum TNF alpha increased
      significantly in the model group, however, the serum TNF alpha levels in the 2
      bicyclol groups were significantly lower than that of the model group. The liver
      TGF beta 1 level in the model group was 4 times that of the normal control group.
      The liver TGF beta 1 level in the 2 bicyclol groups were significantly lower than
      that of the model group. One month after the administration of carbon
      tetrachloride to mice the serum ALT and AST increased and A/G decreased
      significantly. However, in the 2 bicyclol groups the serum ALT and AST were
      significantly lower and the A/G ratio was significantly higher in comparison with
      the model group. The mitochondrial GSH decreased by 34% and the mitochondrial MDA
      increased by 60% in the model group. The mitochondrial GSH was normal in the 2
      bicyclol groups and the MDA level was significantly lower than that of the model
      group. The fluidity and swelling ability of mitochondrial membrane significantly
      decreased in the model group mice and the fluidity and swelling ability of
      mitochondrial membrane in the 2 bicyclol group mice were relatively normal.
      Twelve and twenty-four hours after the damage by carbon tetrachloride the binding
      activity of nuclear NF kappa B remained very high in the model group mice and was
      significantly lower in the 2 bicyclol group mice in comparison with the model
      mice. CONCLUSION: Bicyclol alleviates CCl(4)-induced liver fibrosis by its anti
      peroxidation and anti-inflammation functions and regulation of NF-kappa B DNA
      binding activity.

PMID- 15730627
TI  - [Ascorbic acid inhibits the formation and function of osteoclasts from RAW264.7
      cells induced by receptor activated nuclear factor kappaB ligand in vitro].
AB  - OBJECTIVE: To observe the influence of ascorbic acid (AA) on osteoclastogenesis
      induced by receptor activated nuclear factor kappaB ligand (RANKL) in RAW264.7
      cells and to study the mechanism of AA in osteoclast differentiation. METHODS:
      Mouse mononuclear cells of the line RAW264.7 were cultured. AA and/or RANKL were
      added. Cellular respiration of RAW264.7 cells was assayed by MTT cell
      proliferation method. RAW264.7 cells were inoculated and RANKL and AA of
      different concentrations were added. TRAP staining was used to observe the
      formation of osteoclasts. RAW264.7 cells were inoculated on OAAS, RANKL and AA
      were added. The number of bone absorption pits was counted. RT-PCR was used to
      measure the expression of RANK, matrix metalloproteinase 9, TRAF6, TRAP, integrin
      alpha v, integrin beta 3, cathepsin K, and carbonic anhydrase II (CA II).
      RESULTS: AA of the concentration of 500 microg/ml significantly inhibited the
      proliferation of RAW264.7 cells (0.13 +/- 0.05 vs 1.11 +/- 0.22, P < 0.05). RANKL
      significantly inhibited the proliferation of RAW264.7 cells as well (1.58 +/-
      0.22 vs 1.26 +/- 0.17). AA showed no synergistic action to RANKL. AA alone could
      not induce the formation of TRAP-positive osteoclasts from RAW264.7 cells and 0
      approximately 100 microg/ml AA inhibited the RANKL-induced formation of
      osteoclast-like multinuclear cells from RAW264.7 cells. AA alone up-regulated the
      mRNA expression of CA II, cathepsin K, and TRAP by 10, 1.5, and 1.5 times
      respectively. RANKL plus AA significantly down-regulated the mRNA expression of
      CAII and RANK by 60% and 20% respectively. No bone absorption pit was seen after
      addition of AA. The number of pits on OAAS after addition of AA + RANKL was
      significantly lower than that after addition of RANKL alone (P < 0.05). Western
      blotting showed that no difference was seen in the protein expression of CA I
      between the RANKL group and the control group, however, the protein expression of
      CA II in the low concentration AA + RANKL group was significantly lower than that
      in the RANKL alone group (P < 0.05). CONCLUSION: AA directly inhibits RANKL
      induced osteoclast formation and its function in vitro.

PMID- 15730628
TI  - [pCKM-mPTH recombinant plasmid therapy for hypoparathyroidism: an in vivo
      experimental research with rats].
AB  - OBJECTIVE: To investigate the effect of gene therapy with pCKM-mPTH recombinant
      plasmid on hypoparathyroidism. METHODS: Thirty male Sprague Dawley rats were
      randomly divided into three groups: group A, undergoing fake operation and then
      injection of normal saline into the quadriceps muscle of the left leg; group B,
      undergoing parathyroidectomy and injection of blank pcDNA3.1(+) plasmid into the
      quadriceps muscle of the left leg; and group C, undergoing parathyroidectomy
      injection of pCKM-mPTH plasmid containing gene of mutated proparat-hormone into
      the quadriceps muscle of the left leg. Peripheral blood was collected from each
      rat before operation and 3, 5, 6, 7, 9, 12, 15, 20 and 30 days after operation.
      Radioimmunoassay was used to detect the level of parathyroid hormone. RESULTS:
      The level of paratheproid hormone (PTH) of the group B was 10.61 ng/dl +/- 0.86
      ng/dl before injection of blank plasmid and gradually decreased after the
      injection, for example, 10.39 ng/dl +/- 0.36 ng/dl 1 day after the injection and
      9.45 ng/dl +/- 2.64 ng/dl 60 days after the injection. The level of PTH of the
      group C was 10.75 ng/dl +/- 0.45 ng/dl before the injection of pCKM-mPTH plasmid
      and gradually increased after the injection, for example, 28.39 +/- 0.22 ng/dL 1
      day after the injection, significantly higher than that before the injection,
      peaked on the 6th day (43.28 ng/dl +/- 2.45 ng/dl), then gradually decreased, and
      reached 15.32 ng/dl +/- 0.26 ng/dl on the 60th day. However, the levels of PTH in
      the group C at any time-point were all significantly higher than those of the
      group B (all P < 0.01). Symptoms of hypoparathyroidism were not observed in the
      rats of the group C. CONCLUSION: pCKM-mPTH recombinant plasmid therapy is
      effective in treatment of hypoparathyroidism.

PMID- 15730629
TI  - [Effect of propofol on the activation of nuclear factor-kappa B and expression of
      inflammatory cytokines in cerebral cortex during transient focal cerebral
      ischemia-reperfusion: experiment with rats].
AB  - OBJECTIVE: To investigate the effect of propofol on the activation of nuclear
      factor-kappa B (NF-kappa B) and the expression of inflammatory cytokines, such as
      interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and intercellular
      adhesion molecule-1 (ICAM-1) in cerebral cortex during transient focal cerebral
      ischemia-reperfusion, and to discuss the probable mechanism of its protective
      effect. METHODS: Ninety male Wistar rats were randomly divided into 3 equal
      groups: sham operation group undergoing sham operation; ischemia/reperfusion
      (I/R) group undergoing thread embolism of the left middle cerebral artery
      occlusion (MCAO) to cause focal ischemia for 2 hours and then undergoing
      reperfusion; and propofol group undergoing peritoneal injection of propofol 2
      hours before the ischemia-reperfusion of MCAO. Then the rats in the 3 groups were
      re-divided into subgroups of 5 rats, totally 18 subgroups, to be decapitated 2,
      3, 6, 12, 24, and 72 hours after reperfusion for the latter 2 groups, and their
      brains were taken out and fixed. Immunohistochemistry was used to detect the
      translocation of NF-kappaB in the neurons and the expression of IL-1, TNF-alpha,
      and ICAM-1 in the brain. Western blotting was used to detect the expression of NF
      kappa B. The opposite non-ischemic cortexes were used as controls. RESULTS: Two
      to 24 hours after the reperfusion NF-kappaB was significantly translocated from
      the cytoplasm into the nucleus; however, NF-kappa B remained in the cytoplasm of
      bilateral cortexes in the sham operation groups, and the nonischemic cortexes in
      the I/R and protofol groups. The translocation of NF-kappa B from cytoplasm into
      nucleus was significantly inhibited in the ischemic cortex of the propofol group.
      The expression values of NF-kappa B in the nuclei of ischemic cortexes in the I/R
      group 2 to 24 hours after reperfusion were significantly higher than those in the
      sham operation group and the nonischemic cortexes of the I/R and propofol groups
      (all P < 0.01). The expression values of NF-kappa B in the ischemic cortex of the
      propofol group 2 to 24 hours after reperfusion was significantly lower than that
      of the I/R group (all P < 0.05). The expression values of IL-1, TNF-alpha, and
      ICAM-1 in the ischemic cortexes were significantly higher than that in the cortex
      of the sham operation group and those in the nonischemic cortexes of the I/R
      group and propofol group (P < 0.01 or P < 0.05) and the expression values of IL
      1, TNF-alpha, and ICAM-1 in the propofol group were all significantly lower than
      those in the I/R group (all P < 0.05). CONCLUSION: Propofol inhibits the
      inflammatory reaction by inhibiting the NF-kappa B activation during focal
      ischemia-reperfusion which may be one of the mechanisms of its neuroprotective
      function.

PMID- 15730638
TI  - [Chemotherapy of advanced stomach cancer].

PMID- 15730636
TI  - [A multicenter study of efficacy and safety of oseltamivir in the treatment of
      suspected influenza patients].
AB  - OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of
      suspected influenza patients. METHODS: A randomized, open, control and multiple
      center trial was conducted among 1176 individuals with suspected influenza. They
      were randomized either to oseltamivir group (oseltamivir 75 mg, twice daily for 5
      days) or control group who were given symptom relief medicine. RESULTS: No
      difference was found between two groups in influenza symptoms of the patients (P
      > 0.05) before the treatment. (1) Oseltamivir treatment significantly reduced the
      duration of fever about 25 hours post treatment. (2) The AUC score of other
      symptoms was decreased by 160.21 (about 30.21%), and the duration was shorten by
      20 hours. (3) The ratio and duration of antibiotic use in oseltamivir group were
      less than that of control group (P < 0.0001 and P < 0.05). (4) The incident rate
      of second generation influenza in oseltamivir group was also less than that of
      control group (P < 0.0001). (5) Secondary complications such as bronchitis,
      sinusitis and pneumonia occurred 3.23% in Oseltamivir group and 4.16% in the
      control group (chi(2) = 1.209, P = 0.272). (6) Digestive symptom such as light
      nausea were occur in patients who took oseltamivir, there was no difference of
      side effects rate between two groups (5.18% and 4.16%, chi(2) = 0.680, P =
      0.410). (7) 75.68% (28) were confirmed with positive result of virus test in 37
      suspected influenza patients. CONCLUSION: Our data suggests that Oseltamivir is
      effective and well tolerated in suspected influenza patients. It can reduces the
      duration and severity of influenza symptom and fever, decrease the incidence of
      suspected influenza in the contacted population, antibiotic using, and with light
      side-effect.

PMID- 15730639
TI  - [Neoplastic multicellular drug resistance modulated by cell adhesion].

PMID- 15730642
TI  - [Advances in the study on the management and molecular mechanism of early
      postburn myocardial injury].

PMID- 15730643
TI  - [To advocate the study on early postburn internal organ injury].

PMID- 15730644
TI  - [Mechanism of p38 mitogen-activated protein kinase in postburn acute pulmonary
      injury in scalded rats].
AB  - OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (MAPK)
      signal transduction pathway in the production of the proinflammatory factors such
      as tumor necrosis factor (TNF-alpha) and interleukin 1beta (IL-1beta) in lungs
      and in the pulmonary endothelial cell injury in severely scalded rats. METHODS:
      Forty eight adult healthy SD rats were randomly divided into three groups with 16
      rats in each group, i.e. sham, burn and burn with SB203580 treatment groups. The
      changes in the TNF-alpha and IL-1beta contents in serum and bronchoalveolar
      lavage fluid (BALF), the von Willebrand factor (vWF) contents in plasma and
      pulmonary microvessels and pulmonary activating protein (AP-1) activity were
      determined at 24 postburn hours (PBH). RESULTS: Compared with those in sham
      group, the TNF-alpha and IL-1beta contents in serum and BALF and the vWF content
      in plasma (194.2% +/- 28.3% vs 93.2% +/- 14.3%) at 24 PBH in burn group increased
      significantly (P < 0.01), whereas vWF content in pulmonary microvessel decreased
      obviously (1.1 +/- 0.3 vs 3.3 +/- 0.4, P < 0.01). In addition, the pulmonary AP-1
      activity also increased at 24 PBH. Nevertheless, all the above indices improved
      obviously in burn with SB203580 (inhibitor of p38 MAPK signal transduction
      pathway) treatment group when compared with those in burn group. CONCLUSION: AP-1
      might mediate the production of proinflammatory factors, such as TNF-alpha and IL
      1beta in lungs leading to pulmonary vascular endothelial injury, after being
      activated by activated p38 MAPK.

PMID- 15730645
TI  - [Effect of burn serum on the nuclear translocation of monocytic NF-kappaB
      p50/p65].
AB  - OBJECTIVE: To investigate the effects of burn serum on nuclear translocation of
      monocytic NF-kappaB heterodimers p50/p65 and the degradation of inhibiting kappaB
      (IkappaBalpha), so as to further explore the role of burn serum on the activation
      of monocytes. METHODS: Peripheral blood monocytes (PBMCs) isolated from healthy
      volunteers were employed as the target cells. The cells were stimulated by the
      serum from healthy volunteers and burn patients, and by burn serum together with
      pyrrolidine dithiocarbamate (PDTC). Sera from normal healthy volunteers were
      taken as control. The nuclear translocation of monocytic p50 and p65 at 30th,
      60th, 120th and 480th post stimulation minutes (PSM) was observed with laser
      confocal microscopy. The degradation of monocytic IkappaBalpha protein at 30th,
      60th, 90th and 120th PSM was determined by Western blot. RESULTS: Compared to
      that in control group, the nuclear translocation of monocytic p50 and p65 took
      place 30 min after the PBMCs were stimulated by burn serum, peaking at 30 to 60
      min, but it gradually recovered to pre-stimulation state at 2 hrs with decreased
      intra-nuclear collection. Meanwhile, the IkappaBalpha degradation occurred within
      30 min after PBMCs being stimulated by burn serum, and it peaked at 60 mins.
      However, IkappaBalpha gradually reappeared in the cytoplasm after 2 hrs of
      stimulation. PDTC (an antioxidants) could effectively inhibit monocytic
      IkappaBalpha degradation and nuclear translocation of NF-kappaB induced by burn
      serum. CONCLUSION: Burn serum could induce nuclear translocation of p50 and p65
      components of NF-kappaB in monocytes into the nucleus and degradation of
      IkappaBalpha, leading ultimately to the secretion of cytokines from the PBMCs.

PMID- 15730646
TI  - [Changes in uncoupling protein-2, 3 mRNA expression in the scalded rats after
      escharectomy at different post scalding stages].
AB  - OBJECTIVE: To investigate the expression of uncoupling protein (UCP)-2, 3 mRNA in
      skeletal muscle of the scalded rats after escharectomy at different post scalding
      stages. METHODS: One hundred and twenty Wistar rats were employed in the study,
      in which 8 served as normal control (C) and 112 were subjected to 30% TBSA 3rd
      degree scalding and then again, divided into 4 groups. The rats in A group were
      sacrificed on 8th, 24th, 96th, 120th and 168th post scalding hours (PSHs) without
      escharectomy. The rats in B group underwent escharectomy at 8 PSH, and those in C
      group underwent escharectomy at 24 PSH. All the rats in both groups were
      sacrificed on 96, 120 and 168 PSHs after escharectomy, Escharectomy was performed
      at 96 PSH in rats of D group, and they were sacrificed on 120 and 168 PSHs after
      escharectomy. The serum levels of leptin and TNFalpha, and the expression level
      of UCP2 mRNA were determined at all time points in all groups of rats. RESULTS:
      (1) The serum levels of leptin in A group were obviously lower than that in C
      group (P < 0.01) during 24 approximately 168 PSHs, while those in B, C and D
      groups were much higher than those in A group (P < 0.01) during 24 approximately
      168 PSH. (2) The serum TNFalpha levels in A group at all time points were higher
      than that in control group, while that in B group at all time points were lower
      than that in A group (P < 0.05 or 0.01), and that in C group at 168 PSH was lower
      than that in A group (P < 0.05). (3) The UCP2 mRNA expression in skeletal muscle
      in A group was increased evidently since 8 PSH (P < 0.01), peaking at 24 PSH and
      lowering thereafter, while that in B and C groups at 168PSH was significantly
      lower than that in A group at the same time points (0.32 and 0.35 vs 0.71, P <
      0.05). The trend of the change in UCP3 mRNA expression in skeletal muscle was
      similar to that of UCP2. CONCLUSION: The postburn up-regulation of UCP mRNA
      expression might play important roles in the increase of metabolic rate.
      Escharectomy during shock stage could lower down the expression of UCP2 and UCP3
      mRNA expression, and it could be beneficial by lowering metabolic rate.

PMID- 15730649
TI  - [Experimental study on the induction of endothelial apoptosis by burn serum and
      subeschar tissue fluid].
AB  - OBJECTIVE: To explore the molecular mechanism of apoptosis of the human umbilical
      vein endothelial cells (HUVECs) induced by burn serum and subeschar tissue fluid.
      METHODS: In vitro cultured HUVECs were randomly divided into A (treated by normal
      serum, n = 6), B (treated by burn serum, n = 6) and C (treated by subeschar
      tissue fluid, n = 6) groups. The change in cellular nuclear morphology was
      determined by Hochst 33258 fluorescent staining, and the apoptotic rate was
      calculated at 24th and 36th post treatment hours (PTHs). The DNA ladder strips
      were observed with agarose electrophoresis at 12th and 24th PTH. The activity of
      caspase-3, 8, 9 was assayed by caspase colorimetric assay kit at 12 PTH. RESULTS:
      It was found that nuclei appeared to be condensed and highly fluorescent granular
      in form in B and C groups. The nucleic apoptotic rate in B and C groups was (38.9
      +/- 7.3)% and (49.5 +/- 6.5)%, respectively, which was evidently higher than that
      in A group (P < 0.01). The DNA ladder strips could be found by agarose
      electrophoresis in B and C groups. The activity of caspase-3, 8, 9 in B and C
      groups was significantly higher than that in A group after 12 PTHs (P < 0.01).
      CONCLUSION: Burn serum and subeschar tissue fluid might induce apoptosis of HUVEC
      by means of the activation of death receptor and mitochondrial signal pathways
      simultaneously.

PMID- 15730647
TI  - [An experimental study on large fragment deletion of rat myocardial mitochondrial
      DNA during early postburn stage].
AB  - OBJECTIVE: To investigate the influence of peroxidative injury in rat myocardium
      on the mitochondrial DNA (mtDNA) during early postburn stage. METHODS: Thirty-six
      Sprague-Dawley (SD) rats were employed in the study and were randomly divided
      into sham scald (SS) and scald groups. The rats in scald groups were inflicted
      with 30% TBSA III degree scalding and were further divided into 1, 3, 6, 12 and
      24 post-scald hour (PSH) groups. The mtDNA deletion was determined by semi
      quantitative PCR. The rat myocardial tissue samples were harvested and
      homogenized and the contents of superoxide dismutase (SOD) and malondialdehyde
      (MDA) were determined. RESULTS: There was no mtDNA deletion in the rat myocardium
      in SS group. Partial or complete large fragment (4.8 kb) mtDNA deletion in the
      rat myocardium was identified at 1, 3 and 24 PSHs (P < 0.05 or 0.01). The SOD
      activity in the rat myocardium significantly decreased at 1 PSH, reaching the
      lowest level (76.90 +/- 8.30 U/mg) at 6 PSH, but the MDA content increased
      evidently at 1 PSH, peaking [(3.17 +/- 0.80) nmol/mg] at 6 PSH (P < 0.05).
      CONCLUSION: Peroxidative injury to the rat myocardium during early postburn stage
      might be the principal cause of the 4834 bp deletion of mtDNA in rat myocardium.

PMID- 15730651
TI  - [Inhibition of the expression of cardiomyocytic hypoxic induction factor-1alpha
      during hypoxic state by double chain siRNA].
AB  - OBJECTIVE: To construct hypoxic induction factor-1alpha (HIF-1alpha) siRNA
      expression cassette containing U6 promoter, alpha HIF-1alpha sense or antisense
      target sequence, and to observe its influence on the expression of cardiomyocytic
      HIF-1alpha during hypoxic state. METHODS: Neonatal murine cardiomyocytes cultured
      in the mixed gas were employed as the hypoxic model and were divided into normal
      control (cultured in normal oxygen), RNAi control (invalidated transfection
      interference sequence IV) and RNAi effective inhibition (effective transfection
      interference sequence, which was further divided into I, II and III groups
      according to the difference of downstream primer) groups. Three pairs (I, II and
      III) of PCR downstream primer containing HIF-1alpha encoded gene fragments (sense
      and antisense) and one pair of randomize sequence (IV) PCR downstream primer were
      designed and synthesized. U6 starter expression frame was constructed by PCR
      method. The cardiomyocytes were transfected simultaneously by sense and antisense
      sequence expression frame. Five plates of the cells were set at each time points
      in each group. The expression of HIF-1alpha mRNA was detected by RT-PCR at 6
      hours of hypoxia. The change in the protein expression level at 1 hour of hypoxia
      was determined by Western blot, and the interference effects were monitored by
      immunohistochemistry. RESULTS: The best inhibition fragment screened was group II
      sequence. After the transfection and hypoxic culture, it was found that the
      cardiomyocytic HIF1alpha mRNA and protein levels in RNAi effective inhibition
      group were evidently lower than those in normal control and RNAi control groups
      (P < 0.01). While the protein inhibition rate (60% - 80%) between the former
      group and normal and RNAi control groups was no difference (P > 0.05).
      CONCLUSION: The expression of the HIF1alpha in hypoxic rat cardiomyocytes could
      be effectively inhibited by our constructed HIF1alpha siRNA expression cassette
      group II.

PMID- 15730652
TI  - [Establishment of an animal model with hypertrophic scar].
AB  - OBJECTIVE: To establish an animal model of hypertrophic scar on the rabbit ears
      and to observe the dynamic process of scar formation on the ventral side of the
      rabbit ears. METHODS: Full skin defect (2 cm x 5 cm in diameter) was created on
      the ventral side of 60 ears in 32 New Zealand white rabbits. 1% silver
      sulfadiazine cream was applied to the wounds, and the dressing was changed once a
      week till wound healing. Four ears without operation were taken as control. Wound
      healing under natural condition was observed continuously for 12 months after the
      operation. The scar proliferation on the rabbit ears was observed by light
      microscope and transmission electron microscope, and the scar index was
      determined by computer image analyzing system. RESULTS: The color, thickness and
      texture of the wounds on the rabbit ears after epithelization underwent a process
      of scar overgrowth, maturation and degeneration. The change in scar index was in
      accordance with the wax and wane of scar proliferation. CONCLUSION: The
      hypertrophic scar formed on the ventral side of rabbit ears after natural healing
      of full thickness skin wounds was similar to that in humans. The results
      indicated that this animal model was ideal for the study of the developmental
      mechanism of hypertrophic scars and for the evaluation of the efficacy of the
      prevention and treatment of hypertrophic scars.

PMID- 15730653
TI  - [Clinical study on the changes in plasma sodium level and blood erythrocyte after
      resuscitation with different fluid regimes at early postburn stage].
AB  - OBJECTIVE: To study the changes in plasma sodium level and blood erythrocyte
      after resuscitation with different fluid regimes at early postburn stage.
      METHODS: One hundred and fifty burn patients admitted to our burn ward were
      randomly divided into three groups based on the different regimes of fluid
      resuscitation, i.e. A (n = 50, resuscitation with balanced salt solution for to
      the patients with middle and small burn area, Na(+) = 130 mmol/L); B (n = 50,
      with the same regime as in group A for those with large burn area), and C (n =
      50, with hypertonic saline resuscitation for those with large burn area, Na(+) =
      174 mmol/L) groups. The fluid supplementation, and changes in plasma sodium level
      and blood erythrocyte count, and the mean corpuscular volume (MCV) were observed
      during 1st to 3rd post burn day (PBD). RESULTS: The average volume of fluid
      supplementation in C group was lower than that in A and B groups (P < 0.01),
      though the average sodium supplementation in C group was higher than that in B
      group within 3 PBDs (P < 0.01). The average plasma level of sodium in B group was
      obviously lower than that in C group within 3 PBDs (P < 0.05). Negative
      correlation between the plasma sodium level and burn index (BI) was observed in A
      and B group on 1 PBD (r = -0.84, P < 0.01). The plasma sodium level was in the
      lower margin of normal range (137.4 +/- 3.9) mmol/L in B group, while that in C
      group was in the higher margin of normal range with obvious difference compared
      with B and C groups (P < 0.05 or 0.01). The MCV in group was lower than that in B
      group on the 1st and 2nd PBD, i.e. (92.1 +/- 4.5) fl vs (95.5 +/- 5.5) fl on the
      1st PBD, and (90.9 +/- 5.4) fl vs (93.2 +/- 6.4) fl on the 2nd PBD, P > 0.05).
      CONCLUSION: The plasma sodium level was stable with milder degree of swelling of
      the erythrocytes when hypertonic saline resuscitation was given to patients with
      large burn area during early postburn stage.

PMID- 15730655
TI  - [The role of homeobox B2 gene in vascular endothelial proliferation and the
      protective effects of VEGF on the endothelia against radiation injury].
AB  - OBJECTIVE: To explore the role of HOXB2 gene in the proliferation of primary
      human umbilical vein endothelial cells (HUVECs) and the protective effects of
      VEGF on the endothelia against radiation injury. METHODS: HUVECs were isolated,
      cultured, subcultured and identified. (1) Liposome coated oligodeoxynucleotide
      (odn) and homeoboxB2 antisense oligodeoxyncleotide (HOXB2asodn) were prepared
      prepared in the concentrations of 0.25, 0.5, 1.0 and 2.5 mg/L for the stimulation
      of HUVEC. (3)H-TdR incorporation test and MTT method were employed to determine
      the proliferation activity of HUVECs after activation. The cell cycle analysis of
      HUVECs was determined by flow cytometry. The expression level of HOXB2mRNA within
      HUVECs was detected by RT-PCR (reverse transcription polymerase chain reaction).
      (2) HUVECs were separately treated with the addition of VEGF in concentration of
      50 microg/L, by radiation in the dose of 6 Gy or 12 Gy (60)Co gamma gamma ray, or
      radiation with 12 Gy (60)Co gamma gamma ray followed by the addition of VEGF in
      dose of 50 microg/L. The cellular morphology was observed and the cellular
      proliferation activity was determined by MTT method. RESULTS: (1) The
      proliferation activity of HUVECs could be markedly inhibited by liposome coated
      HOXB2asodn in comparison to liposome-odn (P < 0.05 or 0.001), and the inhibition
      effect was positively correlated with the increase in asodn concentration. The
      cell ratio in S phase and the expression level of the HOXB2mRNA could be lowered
      by asodn in dose of 2.5 mg/L (P < 0.05 or 0.001). (2) Radiation by (60)Co gamma
      ray could lead to the nuclear enlargement, vacuolation in the cytoplasm,
      multiplicity of nucleus and nuclear swelling. The proliferative activity of
      HUVECs was increased from 0.365 +/- 0.047 and 0.487 +/- 0.022 without radiation
      to 0.557 +/- 0.042 and 0.648 +/- 0.021 24 and 48 hours after 6 Gy radiation
      However it was decreased to 0.263 +/- 0.038 and 0.306 +/- 0.024 (P < 0.01) after
      12 Gy (60)Co gamma ray radiation. Nevertheless, the cell morphology was obviously
      improved and the proliferation was enhanced by the addition of VEGF after 12 Gy
      radiation. CONCLUSION: HOXB2 gene played important roles in the biological
      activities of HUVECs. Small dose (6 Gy) gamma-radiation could promote, but large
      dose (12 Gy) could decrease the mRNA expression of HOXB2 gene in HUVECs. In
      addition, VEGF could protect HUVECs against radiation injury.

PMID- 15730657
TI  - [Experimental study on the inhibition of fibroblast contraction by alpha smooth
      muscle actin fusion protein].
AB  - OBJECTIVE: To investigate the influence of alpha smooth muscle actin fusion
      protein (alpha-SMA-FP) on fibroblast contraction, in order to find a new way to
      control scar contracture. METHODS: Three dimensional gel culture model of
      fibroblasts populated collagen lattices (FPCLs) was employed in the study. The
      fibroblasts were cultured in gel for 5 days. The cells in experimental group were
      processed by alpha-SMA-FP in dose of 5, 10, 50, 100 and 250 mg/L, respectively.
      The cells were therefore divided into E(1), E(2), E(3), E(4) and E(5) groups.
      Blank control was set to be C(1) group, and the cells processed by 250 mg/L of
      alpha-SMA-FP be C(2) group. The contraction rate was calculated by measuring the
      diameters of the gel before and after the procession. The change of contraction
      rate in E5 group was observed after the alpha-SMA-FP being rinsed out.
      Immunofluorescent staining of alpha-SMA-FP was carried out in fibroblasts.
      RESULTS: The contraction rate in C1 and C2 groups showed no difference, being
      (58.6 +/- 3.1)% and (56.2 +/- 4.9)% respectively, while that in E1 to E5 groups
      was (45.56 +/- 4.1)%, (42.3 +/- 4.2)%, (41.8 +/- 3.6)%, (37.6 +/- 5.8)% and (26.4
      +/- 4.7)%, respectively. However, the contraction rate in E5 was (53.3 +/- 5.6)%
      after the alpha-SMA-FP had been rinsed out. The difference of the rates among
      control group and experimental groups, especially in E5 after alpha-SMA-FP being
      rinsed out, was significant (P < 0.05 or 0.01). alpha-SMA-FP was located on the
      fibers of the fibroblasts as shown by staining, while the alpha-SMA was not
      stained. Nevertheless, the staining was obvious in control group. CONCLUSION:
      alpha-SMA-FP could inhibit the contraction of fibroblasts specifically with dose
      dependent effect.

PMID- 15730659
TI  - [Effect of sensory neuropeptide substance P on the differentiation of cultured
      epidermal stem cells in vitro].
AB  - OBJECTIVE: To investigate the effect of sensory neuropeptide substance P (SP) on
      the differentiation of cultured epidermal stem cells (ESC) in vitro,with in vitro
      cultured ESC as the platform. METHODS: ESC from newborn Wistar rats were
      isolated, purified by repeated passages in culture. SP was added for stimulation
      when ESC clone grew. Immunohistochemistry staining with K14 antibody, and flow
      cytometry (FCM) was performed at 0, 24th, 48th, 72nd, 96th, 144th, 192nd, 240th,
      288th, 336th, 384th, 432nd post differentiation hours (PDH) to identify the cell
      groups and to detect if there were transient amplifying cells (TAC) among the
      cells. RESULTS: ESC in culture formed large colonies after SP treatment with
      positive staining for K14, indicating that they were TACs. The results of FCM
      indicated that when ESC were stimulated by SP, TAC colony formation occurred and
      the cell number increased in a constant speed. CONCLUSION: ESC could
      differentiate into TAC by neuropeptide SP induction, and the number of ESC kept
      on a certain level during the process.

PMID- 15730673
TI  - [Advances in burn immune research].

PMID- 15730674
TI  - [More knowledge of immunity involved in burn wound repairment].

PMID- 15730675
TI  - [Study on the anti-maturation features of immature dendritic cells induced by low
      dose of granulocyte macrophage colony stimulating factor].
AB  - OBJECTIVE: To investigate the influence of maturative agents, including
      lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha) and interferon
      gamma(IFN-gamma) on the maturation of immature dendritic cells originated from
      murine bone marrow induced by low dose of granulocyte macrophage colony
      stimulating factor (rm GM-CSF). METHODS: Dendritic cells from murine bone marrow
      progenitors were cultured in low and high doses of GM-CSF for 6 days, and then
      the suspending cells were harvested for the experiment. After 3 days of co
      culture of the obtained DC with low dose rmGM-CSF (GM(low)DC) with LPS, TNF-alpha
      and IFN-gamma, the stimulatory capacity of inducing proliferation of non
      sensitized splenocytes of GM(low)DC in mixed lymphocyte reaction (MLR) was
      observed and compared with that of GM(high)DC. RESULTS: GM(low)DC could not
      activate the non-sensitized splenocytes or induce it into proliferation after 3
      days of co-incubation with LPS, TNF-alpha, IFN-gamma, with the stimulation index
      (SI) lower than 2. Whereas GM(high)DC could strongly activate naive splenocytes
      (SI = 4.71). CONCLUSION: GM(low)DC was resistant to maturation and insensitive to
      the stimulation by LPS, TNF-alpha or IFN-gamma.

PMID- 15730676
TI  - [Influence of escharectomy during shock stage on the systemic and intestinal
      immune function in scalded rats].
AB  - OBJECTIVE: To investigate the influence of escharectomy during shock stage on
      systemic and intestinal immune function and its mechanism in scalded rats.
      METHODS: Ninety-six Wistar rats were employed in the study of which 8 were used
      as normal control group. The donor skin from the trunk in twenty-four rats were
      preserved in liquid nitrogen. The other 64 rats were subjected to 30% full
      thickness scalding, and they were randomly divided into A (n = 24, no treatment
      after scalding), B (n = 24) and C (n = 16) groups. Physiological saline was
      intraperitoneally injected (50 ml/kg) on the 24 post-scalding hours to the rats
      in the B and C groups. The rats in B group underwent escharectomy during shock
      stage, and the excision wounds were covered with the cryo-preserved alloskin. The
      rats in C group received the same treatment as in B group but at 72 post-scalding
      hours. The change in the proliferative ability of splenic lymphocytes, the plasma
      and intestinal tissue content of interleukin 2 (IL-2), the contents of sIgA in
      intestinal mucus, and the content of DAO in the intestinal tissue were observed
      on 2, 4 and 8 post burn days (PBD) in A and B groups and also on 4 and 8 PBD in C
      group, respectively. RESULTS: The splenocytic proliferative ability, IL-2 level
      in the plasma and intestinal tissue, and the sIgA content in intestinal mucus in
      the rats in A, B and C groups were lower than that in control group at all time
      points (P < 0.05). The proliferative ability of splenic lymphocytes in B group on
      4 and 8 PBD and in C group on 8 PBD respectively was similar to that in control
      group. Whereas the IL-2 content in plasma and in intestinal tissue was higher in
      B and C groups than that in A group (P < 0.01). The sIgA content in intestinal
      mucus in B group was twice of that in C group respectively [(3.51 +/- 2.14) mg/g
      vs (1.40 +/- 0.64) mg/g, (3.03 +/- 0.95) mg/g vs (1.52 +/- 1.26) mg/g (P < 0.05
      or P < 0.01)] on 4 and 8 PBD. The DAO activity in the intestinal tissue in A
      group was lower than that in control and B group (P < 0.05) on 4 and 8 PBD.
      CONCLUSION: Escharectomy during shock stage might be beneficial to the recovery
      of the systemic and intestinal immune functions in rats with scalding injury.

PMID- 15730677
TI  - [Experimental study on the antibacterial effects of zirconium phosphate gauze
      loaded with silver on the common bacteria on rat burn wound].
AB  - OBJECTIVE: To investigate the antibacterial effects of zirconium phosphate gauze
      loaded with silver on rat burn wounds seeded with commonly seen bacteria.
      METHODS: Wistar rats were employed in the study and were scalded and infected.
      The minimum inhibition concentration (MIC) and minimum bactericidal concentration
      (MBC) of zirconium phosphate loaded with silver were determined by double
      dilution in tubes. The effect on wound healing and the subeschar bacterial count
      of the rat burn wounds were observed after the wounds had been covered by gauze
      loaded with zirconium phosphate and silver, and also with the gauze which has
      been rinsed for 20 times. RESULTS: The MIC of silver loaded zirconium phosphate
      on Staphylococcus aureus, Pseudomonas aeruginosa and E. coli were 8, 8 and 16
      mg/L, respectively, while the MBC were 16, 8 and 32 mg/L, respectively. The
      subeschar bacterial count in the burn wounds with the gauze with silver loaded
      zirconium phosphate was ten times lower than that in those which were treated
      with gauze with SD-Ag and 100 times lower than that with ordinary gauze. But
      there was no difference in the bacterial count between the wounds which were
      treated with fresh gauze with silver loaded zirconium phosphate and that with the
      gauze which has been rinsed for 20 times (P > 0.05). Furthermore, wound healing
      seemed to be better with the gauze with silver loaded zirconium phosphate when
      compared with those by the other two kinds of gauze. CONCLUSION: The silver
      loaded zirconium phosphate was found to be bacteriocidal against bacteria
      commonly seen in the burn wounds.

PMID- 15730680
TI  - [The influence of the application of cytotoxic lymphocyte antigen 4-Ig adenovirus
      on the burn wounds with alloskin grafting on the murine immune function].
AB  - OBJECTIVE: To investigate the influence of local application of cytotoxic
      lymphocyte antigen 4-Ig (CTLA4-Ig) adenovirus on the burn wound with alloskin
      grafting upon the murine immune function. METHODS: Sixty BALB/c mice were
      randomly divided into A (operation control), B (CTLA4-Ig transfection) and C
      (normal control) groups, with 20 mice in each group. Skin wounds (full-thickness
      loss) sized 1.5 cm x 1.5 cm were created on the backs of mice in A and B groups.
      Then the skin grafts of the same size obtained from C57BL mice were grafted into
      the skin wounds. 0.1 g of cross-linking polyacrylic resin (carbomer cream)
      without adenovirus was daubed onto the wounds in A group, and the same amount of
      carbomer cream with adenovirus in titers of 5 x 10(9)/L was daubed onto the
      wounds in B group, while no treatment was given in C group. 1 ml of 10% SRBC
      (sheep red blood cell) was injected intraperitoneally to all the mice of the
      three groups on the 1st post injury day (PID). Splenocytes from BALB/c, C57BL and
      Kunming mice were harvested for mixed lymphocyte culture on 7, 14, 21 and 28
      PIDs. Agglutination assay was used in the same time to detect the SRBC antibody
      titers. RESULTS: The reaction of murine splenocytes in B group to the donor
      (C57BL) splenocytes was suppressed in a specific way (P < 0.05) within 14 PIDs.
      There was no difference in the titers of anti-SRBC antibody among the 3 groups (P
      > 0.05). CONCLUSION: Local application of CTLA4-Ig recombinant adenovirus
      exhibited no influence on the murine humoral immunity, but might induce systemic
      and specific T cell tolerance in immunity system.

PMID- 15730678
TI  - [Experimental study on the role of cytokines and keratinocytes in the survival
      mechanism of auto and allogeneic mixed skin grafting].
AB  - OBJECTIVE: To explore the role of cytokines and keratinocytes in the survival
      mechanism of mixed auto and allogeneic skin grafting. METHODS: Thirty-six SD rats
      were employed in the study. The rat model with mixed auto and allogeneic skin
      grafting and mixed human epithelial and lymphocytic culture (MELC) model were
      established. The change of IL-10 in the serum and the supernatant of the cultured
      tissue sample from the local wound was observed after the mixed skin grafting in
      scalded rats. And the role of epithelium in the induction of immunosuppression in
      vitro was monitored. RESULTS: The serum IL-10 content in the rats with mixed skin
      grafting (25.89 +/- 2.82 ng/L) at 7 postoperative day (POD) was evidently higher
      than that in normal rats (14.20 +/- 2.43 ng/L) (P < 0.05). The IL-10 content in
      the culture supernatant of rat tissue samples exhibited evident different during
      4-14 PODs (P < 0.05-0.01), while which was no difference to that in normal rat on
      21st and 28th POD. The inhibiting effects of autologous epithelia and
      keratinocytes in MELC system were correlated with their dosage. After the adding
      of autologous keratinocytes to MELC system the cytokines secreted from Th1 could
      induce the secretion of cytokines from Th2 by IL-10 mediation. This effect could
      be corrected by the addition of monoclonal antibody of IL-10. CONCLUSION: The
      keratinocytes inlayed in the autoskin during mixed grafting could increase the
      local IL-10 level by activating Th2 cells, which might be one of the important
      reasons of the survival of mixed skin grafting.

PMID- 15730682
TI  - [Clinical study on the relationship among the dermis, fat dome and postburn
      hyperplastic scar formation].
AB  - OBJECTIVE: To explore the influence of dermal defect and fat dome structure
      destruction in burn wounds on the formation of hyperplastic scar. METHODS: Fifty
      two wounds in 24 burn patients with deep partial thickness burn indicating
      tangential excision in the extremities were enrolled in the study, and they were
      divided into three groups according to the extent of exposure of dermal fat
      granules, i.e. A (without fat exposure), B (with little fat exposure) and C (with
      much fat exposure) groups. These three groups were subdivided into A1 (without
      grafting), A2 (grafting with razor thin skin), B1 (without grafting), B2 (with
      razor thin skin grafting), C1 (without grafting) and C2 (with split-thickness
      skin grafting) groups, with 9 wounds in each group. The dermal depth and exposure
      rate of the fat granules in each group were measured and analyzed by KS400
      photography analysis apparatus. The follow-up conditions of the scars 6 months
      after operation were evaluated with Vancouver remark system by Vancouver score
      assessment. RESULTS: There was obvious difference in the dermal depth and
      exposure rate of the fat granules among all the groups (P < 0.05 or 0.01). The
      fat exposure rate was positively correlated with the extent of the dermal defect
      (gamma = 0.554, P < 0.05). The Vancouver score in group A was lower than that in
      B and C groups (P < 0.05), while that in B1 group (3.714 +/- 2.498) was evidently
      higher than that in other groups (P < 0.01). The scar score was lowered when the
      wounds were grafted with the dermis with its thickness similar to the depth of
      the defect, The scar score was increased along with the elevation of fat exposure
      rate (P < 0.05). CONCLUSION: There was a positive correlation between the degree
      of dermal defect and that of hyperplastic scar after burns. The disruption of fat
      dome structure might also be an important factor in the scar development.

PMID- 15730684
TI  - [Experimental study and clinical application of composite skin grafting].
AB  - OBJECTIVE: To explore an ideal skin substitute with its appearance and texture
      similar to normal skin, to repair wounds with full-thickness skin defect.
      METHODS: Composite skin (CS) in question was composed of allo/xenogeneic
      acellular dermal matrix (ADM) and razor thin autoskin. One step skin grafting was
      employed in the experimental study and clinical trial. Razor thin autoskin alone
      was used as the control in the study. Changes in the antigenicity of ADM and the
      reformation of basement membrane (BM) structure at epidermis-dermis junction
      (EDJ) of ADMs were studied at designated time points after the grafting with
      biochemical and immunohistochemical methods. Fifty-three patients with full
      thickness skin defects due to various causes, including scar excision were
      grafted with CS, and survival rate and long-term result were observed. RESULTS:
      The grafted CS survived satisfactory. The reformation of the basement membrane
      structure was clearly observed at the 28th post-graft week. The basement membrane
      cells grew with polarization in an undulating arrangement. There was reformation
      of dermal papillae and ridges. The antigenicity of allo-ADM was obviously lower
      than that of xeno-ADM. Sixty-five out of 70 pieces of CS grafting (92.9%)
      survived totally, two of them survived partially, and three failed due to
      infection. The longest follow-up period was 8 and a half years. The grafted CS
      appeared similar to the normal skin in regard to the texture and color,
      especially allo-ADM, and no evident rejection reaction was seen. CONCLUSION: ADM
      possessed very low antigenicity, thus serving a lasting framework after grafting.
      In addition, it could serve as a "dermal template" for the induction of tissue
      regeneration.

PMID- 15730685
TI  - [The influence of dermal template application on the p53 gene expression and
      apoptosis during wound repairing in burn patients].
AB  - OBJECTIVE: To observe dynamically the influence of the application of dermal
      template on the p53 gene expression and apoptosis during wound repairing in burn
      patients. METHODS: Twenty burn patients were enrolled in the study and were
      divided into experiment (E, n = 11) and control (C, n = 9) groups. The
      escharectomy wounds in patients with 3rd degree burn in E group were covered with
      dermal template overlain with thin split-thickness autograft, while those in C
      group were covered with thin split-thickness autograft only. Specimens were
      harvested from wounds of both groups at 1st, 2nd, 3rd, 4th and 5th post operative
      week (POW). The P53 expression and the apoptosis were assessed respectively by
      immunohistochemistry and by TUNEL kit. The change in cell number was observed
      after HE staining. RESULTS: The P53 expression increased gradually along with the
      wound healing process from 1st to 4th POW, which was significantly higher than
      that in C group at 2nd, 3rd, and 4th POW (P < 0.05), and it reached the peak at
      4th POW. Fibroblasts underwent apoptosis at 1st POW in E group, while apoptosis
      of the endothelial cells occurred mainly at 2nd and 3rd POW. There was obvious
      difference in the rate of apoptosis between the two groups in 3rd and 4th POW (P
      < 0.05). The numbers of fibroblasts and vascular endothelial cells in E group
      were smaller than those in C group. CONCLUSION: Application of dermal template
      overlain with thin split-thickness autograft to wounds could induce P53
      expression and cell apoptosis, thereby reduce scar formation, resulting in
      improvement of the quality of wound healing.

PMID- 15730686
TI  - [Preparation of porcine acellular dermal matrix by low concentration of trypsin
      digestion and repeated freeze-thaw cycles].
AB  - OBJECTIVE: To establish a new method for the preparation of porcine acellular
      dermal matrix. METHODS: The antigenicity of the porcine dermis was weakened by
      removing epidermal and dermal cells from the porcine skin through the digestion
      with low-concentration trypsin and repeated freeze-thaw cycles. Split thickness
      porcine skin was treated with 0.05% trypsin to remove the cells from the
      epidermis and dermis. Repeated freeze-thaw cycles were employed to further weed
      out the residual cells within the dermis. The prepared acellular dermis was then
      examined grossly, as well as histologically, and also by immunohistochemical
      method. RESULTS: No cell could be identified in the prepared porcine acellular
      dermal matrix. The integral basement membrane was preserved on the surface of
      dermal matrix with compact dermal matrix collagen structure. CONCLUSION: Low
      concentration trypsinization and repeated freeze-thaw cycles seemed to be a
      simple and effective method for the preparation of xenogeneic acellular dermal
      matrix.

PMID- 15730687
TI  - [Repairing of soft tissue defects with reverse island skin flap nourished by
      sural nerve vasa vasorum].
AB  - OBJECTIVE: To investigate the clinical outcome of the repairing of soft tissue
      defects of foot with reverse island skin flap nourished by vasa vasorum of the
      sural nerve. METHODS: The skin flap was designed with sural nerve and its vasa
      vasorum as the pedicle, and was harvested from the posterior crural region based
      on the size of the wounds. The defects of the foot in eighteen patients were
      repaired by reverse transplantation of the skin flap. The state of the skin flaps
      was observed post-operatively. RESULTS: All the skin flaps survived. The biggest
      skin flap was 10.5 cm x 16.5 cm in size. The donor sites healed well with
      negligible change in appearance and function. CONCLUSION: Reverse gastrocnemius
      musculocutaneous flap nourished by sural nerve vasa vasorum was easily procured
      with high survival rate, and it could be an ideal flap for the repair of soft
      tissue defect of the foot.

PMID- 15730688
TI  - [Reconstruction of the mentum in the surgical management of cervical scar
      contracture].
AB  - OBJECTIVE: To investigate the effects of the reconstruction of the mentum with
      cervical tissue flaps in the surgical management of postburn cervical scar
      contracture. METHODS: Thirteen postburn patients with severe cervical scar
      contracture and mental deformity were enrolled in the study. The platysma flap (3
      cases), scar tissue flap (6 cases) and cervical deep fascia tissue flap (3
      cases), with the pedicle containing the facial and the superior thyroidal artery,
      were turned upwards to replenish mental soft tissue, and to form new mentum and
      sulcus mentolabialis. The cervical scars were repaired with expanded flap (11
      cases), free flap (1 case) or trapezius muscular flap. RESULTS: The post
      operative cervical configuration was found to be good, and the tissue flaps for
      mental reconstruction healed satisfactorily. Ten patients were followed-up for 6
      to 24 months. All flaps were successful and achieved good results, except that
      scar formation was found in the cervical linear incision in 4 patients.
      CONCLUSION: Transfer of the platysma flaps, scar tissue flaps, or deep cervical
      fascial flaps for the reconstruction of cervical scar were simple and effective.
      The use of cervical scar tissue flaps could not only loose the constructed scar,
      but also beneficial in rectifying the configuration of the chin.

PMID- 15730690
TI  - [The significance of the change of the subfractions in existence of the pulmonary
      surfactant in rabbits with smoke inhalation injury during early postburn stage].
AB  - OBJECTIVE: To investigate the change of the subfractions in existence (big and
      small polymers) of pulmonary surfactant (PS) and their influence on the decrease
      in PS activity during early postburn stage. METHODS: Forty rabbits were employed
      in the study and were randomly divided into pre-burn, 0.5 postburn hour (PBH), 2
      PBH, 6 PBH and 12 PBH groups with 8 in each group. The BALF (bronchial alveolar
      lavage fluid) was harvested from each rabbit. The BALF samples were centrifuged,
      and the supernatant (small polymer) and precipitation (big polymer) were
      harvested for the determination of the contents of the total phospholipids,
      lecithin, total protein, and albumin in both polymers. RESULTS: Compared with
      those in pre-burn group, the above chemical contents of PS in big polymer
      exhibited no change after burn (P > 0.05), but the contents of albumin and total
      protein increased obviously in small polymer (P < 0.01). In addition, all the
      contents in the small polymer increased with the elapse of time. The percentage
      of lecithin in total phospholipids in small polymers decreased along with the
      passage of time. The pre-burn contents of total phospholipids, lecithin, TP,
      albumin, and the percentage of lecithin in total phospholipid in small polymer
      were (2.23 +/- 0.40),(1.54 +/- 0.11), (16.67 +/- 1.34), (3.65 +/- 0.15) mg/ml and
      (77.2 +/- 3.7)%, respectively. The above indices in small polymer were (3.15 +/-
      0.30), (1.77 +/- 0.08), (106.59 +/- 5.50), (11.21 +/- 0.92) mg/ml and (57.2 +/-
      3.5)% respectively at 6PBH. CONCLUSION: The ratio of small to big polymers
      increased obviously, which might be an important factor in inducing the decrease
      in PS activity during early postburn stage leading finally to pulmonary injury.

PMID- 15730709
TI  - [Experimental study of inhibiting CTLL-2 cell apoptosis and enhancing
      cytotoxicity to Yac-1 cell by hammerhead ribozyme].
AB  - OBJECTIVE: To investigate the inhibition role of anti-Fas hammerhead ribozyme on
      Fas expression and Fas-mediated apoptosis in mouse cytotoxic T lymphocyte (CTL)
      cell line--CTLL-2 cells, and explore a novel approach to enhance the ability of T
      cells against leukemia in donor lymphocytes infusion (DLI). METHODS: A hammerhead
      ribozyme targeting the Fas mRNA was synthesized and transfected into CTLL-2 cells
      by electroporation. Fas expression in CTLL-2 cells was detected by using RT-PCR,
      Western blot and flow cytometry, CTLL-2 cells viability was measured by MTT
      assay, caspase-3 proteolytic activity by caspase-3 detection kit, and cell
      apoptosis by flow cytometry. Killing activity of CTLL-2 was detected by LDH
      releasing assay in vitro. RESULTS: Expression of Fas mRNA and protein in CTLL-2
      cells was reduced to 50% after transfection with anti-Fas ribozyme. Being treated
      with anti-Fas antibody (JO(2)), compared with control and mock-transfected cells,
      viability of CTLL-2 cells transfected with anti-Fas ribozyme increased by 1-fold,
      caspase-3 activity and apoptosis rate of ribozyme-transfected cells decreased to
      50% and 37%, respectively, and cell killing activity was enhanced by 2-fold.
      CONCLUSION: Anti-Fas ribozyme can cleave Fas efficiently and inhibit Fas-mediated
      apoptosis of CTLL-2 cells, resulting in improvement of their viability.

PMID- 15730710
TI  - [Effect of soluble anti-CD47 monoclonal antibody on the differentiation and
      function of human dendritic cells].
AB  - OBJECTIVE: To explore the influences of anti-CD47 monoclonal antibody (mAb) B6H12
      on the differentiation and function of cultured dendritic cells (DCs). METHODS:
      Human peripheral monocyte derived DCs were propagated with granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) plus interleukin
      4 (IL-4) in the presence or absence of soluble B6H12. Flow cytometry was used to
      analyze the immunophenotypes of cells, semi-quantitative RT-PCR and ELISA methods
      to analyse the mRNA and protein expression levels of interleukin-12 (IL-12). The
      antigen-presenting function of DCs was determined in one-way mixed leukocyte
      reaction by Brdu-ELISA technique. RESULTS: There was a high expression rate (94%
      approximately 98%) of CD47 molecules in DCs. The cell immunophenotypes in B6H12
      mAb treated and untreated DC groups were as follows: CD80(+) (68.14 +/- 7.41)% vs
      (89.17 +/- 8.59)%; CD86(+) (67.33 +/- 4.71)% vs (87.27 +/- 3.56)%; CD83 (40.08 +/
      14.80)% vs (72.77 +/- 8.68)%; CD1a(+) (66.45 +/- 4.06)% vs (95.93 +/- 3.03)%;
      and HLA-DR (40.67 +/- 13.48) vs (98.97 +/- 1.01)%, respectively. The expression
      levels of mRNA and protein of IL-12 were strongly inhibited in B6H12 mAb treated
      DC (P < 0.01). The quantity of Brdu was also lower in B6H12 mAb treated DC than
      that in untreated DCs (P < 0.01). CONCLUSION: The anti-CD47 McAb exerts a
      negative effect on the maturation and functions of cultured DCs.

PMID- 15730711
TI  - [Effect of natural killer cell on hematopoiesis and immunity recovery in mouse
      allogeneic bone marrow transplantation].
AB  - OBJECTIVE: To study the effect of natural killer (NK)-cell on reconstitution of
      hematopoiesis and immunity in mouse allogeneic bone marrow transplantation (allo
      BMT). METHODS: Lethally irradiated BALB/c (H-2(d)) mice were transplanted with
      C57BL/6 (H-2(b)) bone marrow plus peripheral T cells and/or NK cells. Recipients
      CD34(+) cells and H-2K(b+), CD3(+) and CD19(+) cells were detected by flow
      cytometry, peripheral white blood cell (WBC) by auto-cytometry, and the survival
      rates, engraftment, hematopoietic and immune recovery were observed. RESULTS: In
      the transplantation with NK cell infusion group, the survival rates, the WBC and
      CD34(+) cell counts, and the H-2(b+) and CD19(+) cells were significantly higher
      than that in without NK cell infusion group (P < 0.01). Twenty-eight days after
      transplantation, the CD3(+) cells in the NK cell infusion group [(33.69 +/-
      3.36)%] were lower than that in without [(50.4 +/- 5.06)%] (P < 0.01), and there
      was no longer difference between these groups 60 days after transplantation (P >
      0.05). CONCLUSION: In mouse allo-BMT, alloreactive NK cell enhances engraftment,
      promotes reconstitution of hematopoiesis and immunity and increases survival
      rates.

PMID- 15730712
TI  - [Experimental study of K562 cell apoptosis induced by siRNA].
AB  - OBJECTIVES: To construct a siRNA expression vector pBCR6 that produces siRNA
      against bcr/abl mRNA and detect apoptosis rate of K562 cells after pBCR6
      transfection. METHODS: Template sequence for siRNA was designed, synthesized and
      inserted into an expression vector pSilencer1.0-U6. Restriction analysis and
      sequencing were performed to verify the pBCR6 vector. Then pBCR6 was transfected
      into K562 cells by X-tremeGene Q2. pSilencer1.0-U6 was used as the control. At
      different time point after transfection, apoptosis rate was determined by Tunel
      and Annexin V+ PI with FCM. RESULT: pBCR6 was verified by restriction analysis
      and sequencing. The apoptosis rate of K562 cells markedly increased at 48 and 72
      hour after transfected with pBCR6, and increased in a time-dependent manner [the
      apoptosis rate of transfected K562 cells was (47.80 +/- 1.63)% at 72 hrs, whereas
      the control group was (6.67 +/- 0.37)%, P < 0.0001] No prominent change in
      apoptosis rate was found in the control. CONCLUSION: The siRNA expression vector
      against bcr/abl mRNA was successfully constructed. The pilot study showed that
      pBCR6 could effectively induce K562 cells apoptosis. siRNA may be a new tool for
      molecular target therapy for chronic myelogenous leukemia.

PMID- 15730713
TI  - [In vitro infection of human megakaryocyte precursors by human cytomegalovirus
      (HCMV) and the antiviral effect of HCMV antisense oligonucleotides].
AB  - OBJECTIVE: To explore the suppression effect of human cytomegalovirus (HCMV) on
      megakaryocytes and their precursors and study the antiviral effect of antisense
      phosphorothioate deoxyoligonucleotide (ASON) against HCMV. METHODS: CD34(+) cells
      were induced to proliferate and differentiate committedly to megakaryocytes in a
      semi-solid CFU-MK culture system. Cultured cells and ASON pretreated CD34(+)
      cells were infected by HCMV of AD169 strain. HCMV immediate early protein (IEP)
      DNA and mRNA and UL36 mRNA were detected by PCR and reverse transcription
      polymerase chain reaction (RT-PCR). Cytotoxicity was evaluated by MTT assay.
      RESULTS: HCMV AD169 suppressed the proliferation of megakaryocytes significantly.
      Compared with the mock group, the CFU-MK yields were decreased by 21.6%, 33.8%,
      and 46.3%, respectively, in 3 different titers of virus infected groups (P <
      0.05). The suppression was virus titer dependent. HCMV IEP DNA, HCMV IEP mRNA and
      UL36 mRNA were detected in the colony cells of viral infection group. Compared
      with the infected group by HCMV AD169, UL36Anti treatment at 0.08 micromol/L
      could recover the CFU-MK yields significantly (P < 0.05). In the infected MK,
      which was pretreated with UL36Anti at 0.08 micromol/L, HCMV UL36 mRNA was
      undetectable by RT-PCR. The oligonucleotide MM(1) containing a G-to-C
      substitution in UL36Anti was inactive at 0.08 micromol/L but active at 0.40
      micromol/L. The concentration of UL36Anti necessary to significantly affect cell
      growth was 90.00 micromol/L. CONCLUSIONS: HCMV AD169 infection inhibits the
      proliferation and differentiation of megakaryocytes and their precursors. There
      are early transcriptions of HCMV IE and UL36 protein in infected CFU-MK. The
      specific ASON has a definite anti-HCMV activity.

PMID- 15730714
TI  - [Targeted blockage of STAT5 by a decoy oligodeoxynucleotide inhibits the growth
      and proliferation of K562 cells].
AB  - OBJECTIVES: To investigate targeted blockage of BCR/ABL oncoprotein mediated cell
      transformation by STAT5 decoy oligodeoxynucleotide (ODN), its effect on the
      growth and proliferation inhibition of K562 cells and the related molecular
      mechanisms. METHODS: STAT5 decoy ODN, designed and synthesized in vitro, was
      transfected into K562 cells by cationic lipid. The cell growth curve and colony
      formation assay were used to reflect the growth and proliferation capacity of
      K562 cells, RT-PCR to detect the expression of three genes downstream STAT5.
      RESULTS: Confocal microscopy demonstrated that STAT5 decoy ODN was successfully
      transfected into K562 cells (95.2% positive cells). STAT5 decoy ODN inhibited the
      growth of K562 cells (inhibition rate 77.7%) and their colony formation capacity
      (Decoy ODN treated group 8.3% vs control group 35.7%, P < 0.05) after the
      treatment with STAT5 decoy ODN, the expressions of c-myc, bcl-X(L), cyclin D1
      mRNA were down-regulated by 15.4%, 30.8%, 29.1%, respectively in the K562 cells.
      CONCLUSIONS: STAT5 decoy ODN inhibits the growth and proliferation of K562 cells.
      The mechanisms may be that decoy ODN blocks the transcriptional activation potent
      of STAT5 and down-regulates the expression of these tumor related genes
      downstream STAT5.

PMID- 15730716
TI  - [Detection of WT1 expression in bone marrow of acute leukemia patients with real
      time quantitative RT-PCR].
AB  - OBJECTIVE: To investigate Wilms' tumor gene (WT1) expression levels in bone
      marrow (BM) of acute leukemia patients (ALs). METHODS: A real-time quantitative
      reverse transcriptase polymerase chain reaction (RQ-RT-PCR) method was
      established for detecting WT1 and internal reference GAPDH expression levels in
      BM of 108 ALs and 23 non-leukemia controls by Light Cycler. RESULTS: The median
      expression levels of WT1 in 70 newly diagnosed ALs and 11 relapsed ALs were
      statistically higher than those in 23 ALs in complete remission (CR) and 23 non
      leukemic controls (75.10 and 89.56 vs 2.07 and 1.51 respectively). No statistic
      differences was found between the CR group and control group, nor between the
      newly diagnosed group and relapsed group. Of the 70 newly diagnosed ALs, median
      WT1 expression level of acute granulocytic leukemias was significantly higher
      than that of acute monocytic leukemias (M(5)), but there was no statistic
      differences among the M(1), M(2), M(3) and ALL subtypes. Furthermore the WT1
      levels were not correlated to peripheral WBC counts, BM blast percentage and
      multidrug resistant gene (mdr1) expression at presentation, but correlated to
      chromosome karyotypes. Dynamic analysis of WT1 levels of 2 patients on treatment
      showed that WT1 expression levels predicted relapse. CONCLUSION: WT1 expression
      levels in ALs were strikingly higher than that in non-leukemias. WT1 can be a
      marker for detecting MRD and evaluating therapy efficacy in leukemias.

PMID- 15730717
TI  - [Proliferation inhibition effect of indomethacin on CML cells associated with
      down-regulation of phosphorylated STAT1/STAT5 and inhibition of COX-2
      expression].
AB  - OBJECTIVE: To explore the mechanism of anti-proliferative effect of indomethacin
      (IN) on chronic myelogenous leukemia (CML) cells. METHODS: MTT was applied to
      assay CML cells viability under IN intervention. STAT1, STAT5 proteins were
      analyzed by Western blot, the expressions of phosphorylated STAT1 or STAT5 by
      immunoprecipitation combined with Western blot, the cellular localization of p
      STATs proteins by indirect immunofluorescence technique, and the detection of Bcl
      X(L) and COX-2 protein by Western blot. RESULTS: IN could significantly inhibit
      the viability of CML cells. 0 approximately 400 micromol/L of IN could down
      regulate the expression of p-STAT1 or p-STAT5 in a dose-response manner, p-STATs
      were distributed mainly in the nucleus as scattering spots. The expression of COX
      2 protein could be detected in K562 cells. Both Bcl-X(L) and COX-2 proteins could
      be inhibited by IN in a dose-dependent manner. CONCLUSIONS: IN could
      significantly inhibit the proliferation of CML cells, the mechanism of which
      might be related to the suppression of STATs/Bcl-X(L) signal transduction
      pathway. There exists COX-2 protein expression in K562 cells, the anti-leukemia
      effect of IN was possibly dependent on COX-2 pathway.

PMID- 15730718
TI  - [Differential expression of a homing-related molecule repertoire among umbilical
      cord blood, mobilized peripheral blood and bone marrow-derived hematopoietic
      stem/progenitor cells].
AB  - OBJECTIVE: To compare the expression profiles of a set of homing-related
      molecules (HRM) repertoire expressed on hematopoietic stem/progenitor cells
      (HS/PC) from different sources. METHOD: The expression levels of HRM on HS/PC
      from umbilical cord blood (UCB), mobilized peripheral blood (mPB) and bone marrow
      (BM) were assessed using a highly sensitive 4-color flow cytometric analysis.
      RESULTS: UCB-derived CD34(bright) cells, as well as mPB- and BM-derived
      CD34(bright) cells strongly expressed CD44, CD11a, CD18, CD62L, CD31 and CD49d.
      On the other hand, significantly lower expressions of CD49e, CD49f, CXCR-4 and
      CD54 on UCB-derived CD34(bright) and CD34(bright)CD38(-) cells, compared with
      those on mPB- and BM-derived CD34(bright) and CD34(bright)CD38(-) cells, were
      observed. None of UCB-, mPB- and BM-derived CD34(bright) cells expressed other
      chemokine receptors, including CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, CXCR-2, CXCR-3
      and CXCR-5. Another striking finding was that only mPB-derived CD34(bright) cells
      expressed significant levels of both the matrix metalloproteinases MMP-2 ?[(11.4
      +/- 4.9)%?] and MMP-9 ?[(27.6 +/- 7.8)%?]. CONCLUSION: HS/PC from UCB have some
      defects of expression of HRM repertoire, which might partly explain the cause(s)
      of delayed hematopoietic reconstitution after UCB transplant.

PMID- 15730719
TI  - [The effects of interleukin-11 on high-dose methotrexate (HDMTX) induced
      mucositis in Wistar rats].
AB  - OBJECTIVE: To explore the therapeutic effect of interleukin-11 (IL-11) on high
      dose methotrexate (HDMTX) induced mucositis in Wistar's rats, the proliferative
      effect on CEM leukemia cell line and the antitumor effect on HDMTX. METHODS:
      Ninety-five 5-week old, 120 - 150 grams weight Wistar rats were randomly divided
      into five groups. Group A is normal control (n = 15), group B MTX control (n =
      20), group C IL-11 pretreatment group before MTX injection (n = 20), group D (n =
      20) the high dose IL-11 group (475 microg.kg(-1).d(-1)) after MTX injection,
      group E (n = 20) the low dose IL-11 group (150 microg.kg(-1).d(-1)) after MTX
      injection. All rats in group B approximately E were given 1 ml MTX
      intraperitoneally (100 mg/kg). Rats were killed at day 1, 3, 5, 7 after MTX
      injection. The mortality rates, changes of small intestine tissue morphology and
      ultra structure were observed. The proliferation of small intestine crypt cell
      was assayed by proliferating cell nuclear antigen (PCNA) immunohistochemical
      staining. MTT method was used to detect the proliferation of CEM cell line.
      RESULT: IL-11 treatment resulted in a significant increase of survival of HDMTX
      treated rats, increased of small intestinal villus length and villus/crypt ratio.
      IL-11 administration was associated with enhancement of small intestine mucosa
      recovery after HDMTX therapy. Group C showed a greater effect than group B (P <
      0.01). IL-11 had no effect on CEM cell proliferation. CONCLUSION: IL-11 has a
      significant mitigating effect on high-dose MTX induced intestinal mucositis in
      rat, and significantly increase the survival of the rats. IL-11 could be safely
      used in the HDMTX treatment of childhood acute lymphocyte leukemia.

PMID- 15730728
TI  - [New recognition of a role of dyslipidemia and lipid-lowering treatment in
      pathogenesis of renal disease].

PMID- 15730729
TI  - [How to choose the duration of prone-position ventilation in patients with acute
      respiratory distress syndrome caused by pulmonary or extrapulmonary diseases?].
AB  - OBJECTIVE: To determine the different effect of prone-position ventilation (PPV)
      in patients with acute respiratory distress syndrome (ARDS) resulting from a
      pulmonary cause (ARDSp) and that from an extrapulmonary cause (ARDSexp) on
      oxygenation, respiratory mechanics and hemodynamics. To determine an appropriate
      duration of ventilation in the prone position in the two groups. METHODS: Nine
      ARDSp patients and seven ARDSexp patients within 3 days of onset of ARDS were
      included in this study which were classified as two groups. The patients were
      placed in prone position for 2 h. The effect of different time (pre-PPV, PPV 0.5
      h, PPV 2 h) on oxygenation, respiratory mechanics and hemodynamics were observed.
      Lung computerized tomography (CT) was obtained in both the supine position and 10
      min after prone position. RESULTS: Compared with pre-PPV, in ARDSp, partial
      pressure of oxygen in artery (PaO(2))/inhaled oxygen concentration (FiO(2)) was
      not increased after 0.5 h, and increased only after 2 h in the prone position
      (130.6 +/- 36.2 to 165.1 +/- 72.3, P < 0.05). But in ARDSexp, PaO(2)/FiO(2) was
      significantly increased after 0.5 h and 2 h in the prone position (116.5 +/- 55.0
      to 163.2 +/- 46.4 and 182.7 +/- 87.7, P < 0.05). After 0.5 h in the prone
      position the responding ratio of ARDSexp was higher than ARDSp (7/7 vs 1/9, P =
      0.0007). After 2 h, no significant difference of responding ratio was found
      between the two groups (6/7 vs 6/9, P = 0.392). The changes of the PaO(2) were
      similar to the PaO(2)/FiO(2). The PaCO(2) and the static respiratory system
      compliance (Cstrs) did not differ significantly between the prone position and
      the supine position in the two groups. In ARDSp, the airway resistance was (10.8
      +/- 1.4) cm H2O.s(-1).L(-1) in the supine position, and it was significantly
      decreased after 2 h in the prone position (8.4 +/- 1.8) cm H2O.s(-1).L(-1) (P <
      0.05). Chest CT scans of ARDSp and ARDSexp patients showed marked difference.
      CONCLUSIONS: PPV could be used to improve severe hypoxemia of ARDS. It improved
      the PaO(2)/FiO(2) ratio rapidly in ARDSexp, but in ARDSp the improvement took a
      longer time.

PMID- 15730731
TI  - [Effect of nuclear factor-kappaB on signal transduction of passively sensitized
      human airway smooth muscle cells proliferation].
AB  - OBJECTIVE: To investigate whether nuclear factor-kappaB (NF-kappaB) contributes
      to passively sensitized human airway smooth muscle cell (HASMCs) proliferation,
      and whether it is the downstream factor of activated protein kinase C (PKC).
      METHODS: HASMCs in culture were passively sensitized with 10% serum from
      asthmatic patients, with non-asthmatic human serum treated HASMCs as the control.
      NF-kappaB specific inhibitor pyrrolidine dithiocarbamate (PDTC) and PKC agonist
      phorbol 12-myristate 13-acetate (PMA) were used to intervene HASMCs exposed to
      asthmatic serum and non-asthmatic control serum. The proliferation of HASMCs was
      examined by cell cycle analysis, MTT colorimetric assay and proliferating cell
      nuclear antigen (PCNA) immunofluorescence staining respectively. NF-kappaB
      activity was detected by NF-kappaBp65 immunofluorescence staining and
      electrophoretic mobility shift assay (EMSA) respectively. RESULTS: (1) The
      percentage of S phase, A value, the positive expression rate of PCNA, the
      positive expression rate of NF-kappaBp65 and EMSA value in HASMCs passively
      sensitized with asthmatic serum were (21.78 +/- 2.79)%, 0.466 +/- 0.058, (67.5 +/
      8.5)%, (12.6 +/- 2.2)% and 32 781 +/- 9499 respectively. They were significantly
      increased compared with those of the control serum group (P < 0.05). After
      previously treated with PDTC, the above figures were decreased to (16.37 +/-
      3.05)%, 0.389 +/- 0.035, (53.4 +/- 5.1)%, (4.9 +/- 1.3)% and 3934 +/- 937
      respectively (P < 0.05). (2) After HASMCs were treated with both PMA and
      asthmatic serum, the percentage of S phase, A value, the positive expression rate
      of PCNA, the positive expression rate of NF-kappaBp65 and EMSA value were (25.52
      +/- 3.38)%, 0.572 +/- 0.054, (81.2 +/- 10.2)%, (26.5 +/- 5.0)% and 71 654 +/- 12
      293 respectively. After previously treated with PDTC, the above figures were
      (16.42 +/- 2.72)%, 0.386 +/- 0.031, (54.2 +/- 5.3)%, (5.9 +/- 1.4)% and 4808 +/-
      1084 respectively. The difference was significant (P < 0.05). CONCLUSIONS: NF
      kappaB may contribute to the proliferation of HASMCs passively sensitized with
      human asthmatic serum, which involves the PKC/NF-kappaB signal pathway.

PMID- 15730730
TI  - [The levels and clinical implications of induced sputum interleukin-17 in chronic
      obstructive pulmonary disease and asthma].
AB  - OBJECTIVE: The study aims to investigate the changes of interleukin (IL)-17 in
      induced sputum, and to observe the correlation between concentrations of IL-17
      and the number of inflammatory cells in induced sputum in chronic obstructive
      pulmonary disease (COPD) and in asthma. METHODS: Induced sputum was obtained in
      patients with COPD both during acute exacerbation and stable stage and in asthma
      during acute attack. Healthy nonsmoking volunteers were included as controls. The
      concentrations of IL-17 in induced sputum were measured by enzyme-linked
      immunosorbent assay. RESULTS: The concentrations of IL-17 both in patients with
      COPD during acute exacerbation and with asthma were significantly higher than
      that in the control subjects (P < 0.001). The levels of IL-17 in patients with
      COPD during acute exacerbation positively correlated with that of IL-8 (r =
      0.381, P = 0.038) and with the percentage of neutrophils (r = 0.446, P = 0.010)
      respectively. There was also a positive correlation between the concentrations of
      IL-17 and the numbers of eosinophils in patients with asthma. CONCLUSION: The
      concentrations of IL-17 in patients with acute exacerbation of COPD and in
      patients with asthma were significantly increased. IL-17 may play a role in the
      airway inflammation in both COPD and asthma.

PMID- 15730732
TI  - [Combined gene therapy enhances collateral vascularization in coronary artery
      occlusion swine model].
AB  - OBJECTIVE: To investigate the efficacy of combined gene transfer of vascular
      endothelial growth factor (VEGF) and angiotensin-1 (Ang-1) in swine coronary
      artery occlusion. METHODS: Swine underwent left thoracotomy followed by ligation
      of left anterior descending coronary artery. Constructed PCD(2)/VEGF and/or
      PCD(2)/Ang-1 eukaryotic expression plasmid was directly injected into the swine
      myocardium. RT-PCR, immunohistochemistry, capillary density and arteriole density
      were used to detect gene expression and biological effect. Coronary angiography
      was done to evaluate collateral circulation of the occluded artery. RESULTS: High
      levels of VEGF and Ang-1 mRNA and protein expression were detected. There was a
      significant increase in the number of capillaries and arterioles as compared with
      a control group (P < 0.05). Capillary density and arteriole density of the
      combination therapy group were higher than those of the swing receiving either
      therapy alone. Coronary angiography showed better collateral circulation in the
      combination therapy group. CONCLUSIONS: Direct injection of PCD(2)/VEGF and
      PCD(2)/Ang-1 can transfect the myocardium and express VEGF and Ang-1 protein.
      Combined gene transfer of VEGF and Ang-1 can increase capillary and arteriole
      number and enhance collateral circulation of the occluded coronary artery more
      effectively.

PMID- 15730733
TI  - [Comparison and analysis of the clinical features of different types of
      gastrointestinal cancers].
AB  - OBJECTIVE: To analysis the clinical features of gastrointestinal (GI) carcinoid
      tumor in different pathological types, and to improve the level of its diagnosis
      and treatment. METHODS: Retrospectively analysis 36 cases of GI carcinoid in
      Peking Union Medical College Hospital from 1982 to 2003, according to the
      International Classification of Disease for Oncology (ICD-O). The 36 cases were
      divided into carcinoid group and malignant carcinoid group. Their clinical
      presentation, metastasis, age, its ratio in gastrointestinal endocrine and non
      endocrine tumor were compared. RESULTS: (1) Ratio: the ratio of GI carcinoid in
      digestive system non-endocrine tumor was 0.35%, in endocrine tumor was 10.20%.
      (2) Age: the mean age of the malignant carcinoid group was (55.8 +/- 12.8) years
      old and carcinoid group was (45.1 +/- 12.0). The age of the malignant carcinoid
      group is significantly higher than that of the carcinoid group. (3) Sites: the
      rectum carcinoid (63%) was the most common site of the overall GI carcinoid, the
      gastric (35%) and colonic (25%) carcinoid in the malignant carcinoid group were
      found more than that in carcinoid group. (4) Metastasis: the lymphonode and liver
      (60%) were most common sites of malignant carcinoid tumor. The ratio of
      metastasis from stomach and colon was higher than that from the other
      gastrointestinal sites. (5) DIAGNOSTIC METHODS: most of the GI carcinoid tumors
      were diagnosed by the colonoscopy. The rectal touch should not be neglected. (6)
      Carcinoid syndrome: The incidence of carcinoid syndrome was quite low and often
      occurred in malignant carcinoid tumor. CONCLUSIONS: The overall incidence of GI
      carcinoid tumor makes up 0.35% of gastrointestinal tumor. It is not common
      disease but not rare. The rectum is most common site of carcinoid tumor. Most of
      the gastric and colonic carcinoid tumor was belonging to malignant. The mean age
      of malignant carcinoid tumor was older with the metastasis of lymphonode and
      liver. The carcinoid syndrome often occurred in malignant carcinoid tumor.

PMID- 15730734
TI  - [The impact of decreased Stat3 activation on 5-fluorouracil resistance of human
      gastric cancer cell line].
AB  - OBJECTIVE: To investigate the relationship between different activation of Stat3
      signaling and the drug resistance mechanisms in two human gastric cancer cell
      lines, 5-fluorouracil (5-FU) resistant cell line and its parental cell line.
      METHODS: Electrophoretic mobility shift assay and Western blot were used to
      detected Stat3 DNA-binding activity and the expression of phospho-Stat3 protein
      in 5-FU resistant cell line SGC7901/R and its parental cell line SGC7901,
      respectively. The mRNA expression of Stat3 and vascular endothelial growth factor
      (VEGF) were analysed with semi-quantitative RT-PCR. The expressive intensity of
      VEGF protein was measured by immunocytochemistry. RESULTS: The constitutive
      activation of Stat3 and the expression of phospho-Stat3 protein were different in
      two human gastric cancer cell lines. Compared with the parental cell line
      SGC7901, the Stat3-DNA binding activity and the expressive intensity of phospho
      Stat3 protein were lower in the drug-resistant cell line SGC7901/R. The
      expression level of Stat3 mRNA was also decreased in drug resistant cell line, so
      did VEGF mRNA and its encoded protein. CONCLUSIONS: The decreased Stat3
      activation in 5-FU resistant human gastric cancer cell line SGC7901/R is related
      to the drug resistance mechanisms and may be correlated with the lower VEGF
      expression.

PMID- 15730735
TI  - [Anti-hypertensive effect of rosiglitazone in non-diabetic essential
      hypertension].
AB  - OBJECTIVE: To investigate blood pressure-lowering effect of rosiglitazone in
      overweight/obese non-diabetic patients with hypertension to explore the
      therapeutic role of insulin sensitizers in the management of essential
      hypertension. METHODS: 89 cases of overweight/obese non-diabetics with essential
      hypertension were enrolled in a 4 weeks open label clinical trial. Rosiglitazone
      8 mg/day were started 2 weeks after withdrawing previously used anti-hypertensive
      medications. Blood pressure was measured at the 2nd and 4th week. Plasma glucose
      and insulin levels during oral glucose tolerance test (OGTT) at baseline and at
      4th week were also determined. RESULTS: After 4 weeks treatment with
      rosiglitazone, the mean systolic and diastolic blood pressure reduced by 17 mm Hg
      (1mm Hg = 0.133 kPa) and 11 mm Hg, respectively. Plasma insulin levels at
      fasting, 1 and 2 hour during OGTT decreased by 27%, 35% and 41%, respectively (P
      < 0.001), whereas insulin sensitivity increased by 30% (P < 0.001). The amplitude
      of reduction of blood pressure was related to the baseline level of blood
      pressure and insulin sensitivity, and family history of hypertension.
      CONCLUSIONS: Rosiglitazone significantly reduces blood pressure in overweight
      and/or obese non-diabetic subjects with hypertension. Randomized controlled
      clinical trial is justified to confirm the therapeutic role of rosiglitazone in
      the management of non-diabetic essential hypertension.

PMID- 15730736
TI  - [Human immunodeficiency virus-1 gag specific CD8+ T cell responses in long-term
      nonprogressors and acquired immunodeficiency syndrome patients].
AB  - OBJECTIVE: To investigate the human immunodeficiency virus (HIV)-1 gag specific
      CD(8)(+) T cell responses in long-term nonprogressors (LTNP) and acquired
      immunodeficiency syndrome (AIDS) patients in China. METHODS: 7 LTNP and 9 AIDS
      patients were included in this study. 11 peptide pools derived from 125
      overlapping peptides spanning the full-length of HXB2 gag were used as antigens.
      HIV-1 specific CD(8)(+) T cell responses in these patients were examined by
      interferon gamma ELISPOT assay, and investigated the relationship between HIV-1
      gag specific CD(8)(+) T cell responses and CD(+) T cell counts and the
      relationship between specific CD(8)(+) T cell responses and viral loads. RESULTS:
      HXB2 could induce HIV-1 specific CD(8)(+) T cell responses in Chinese HIV/AIDS
      patients. The strengths of HIV-1 gag specific CD(8)(+) T cell responses in LTNP
      and AIDS groups were (1212 +/- 796) SFC/10(6) PBMC and (182 +/- 203) SFC/10(6)
      PBMC, respectively. The breadths of HIV-1 gag specific CD(8)(+) T cell responses
      of LTNP group and AIDS group were 3.0 +/- 0.8 and 0.8 +/- 0.7, respectively. The
      values of these two parometers in LTNP group were significantly higher than that
      in AIDS group (P < 0.01). There was a positive relationship between the strength
      or the breadth of HIV-1 specific CD(8)(+) T cell responses and CD(4)(+) T cell
      counts, whereas there was a negative relationship between strength or breadth of
      CD(8)(+) T cell responses and viral loads. CONCLUSIONS: There was a cross
      reactivity between dominant HIV strain in Europe and America and those in China.
      HIV-1 gag specific CD(8)(+) T cell responses may play a protection role during
      disease progression.

PMID- 15730737
TI  - [Epitope mapping of myeloperoxidase antibodies in propylthiouracil-induced
      vasculitis and microscopic polyangiitis].
AB  - OBJECTIVE: To compare the epitopes of antibodies for myeloperoxidase (MPO) in the
      serum from patients with propylthiouracil (PTU) induced vasculitis and
      microscopic polyangiitis (MPA). METHODS: Serum samples from patients with PTU
      induced vasculitis (n = 10) and MPA (n = 10) were collected and used to inhibit
      monoclonal antibodies against human MPO 3D8 and 6B9 and then affinity was
      purified, horseradish peroxidase conjugated and human MPO antibodies determined
      (Pab1-HRP, Pab2-HRP) in a competitive inhibition ELISA system using soluble human
      MPO as solid phase ligands. The Pab1-HRP and Pab2-HRP were affinity purified from
      plasma exchanges of a patient with PTU-induced vasculitis and a patient with MPA.
      The inhibition rates were evaluated and compared between PTU group and primary
      MPA group. RESULTS: In PTU group, all the 10 serum samples could inhibit 3D8; the
      average inhibition rate was 44.7%, 9/10 of the serum samples could inhibit 6B9;
      the average inhibition rate was 35.6%; In MPA group, all 10 serum samples could
      inhibit 3D8 and 6B9; the average inhibition rates were 68.4% and 62.2%. Serum in
      both groups could inhibit Pab1-HRP and the inhibition rates were both more than
      80%; the average inhibition rate for Pab2-HRP in MPA group was significantly
      higher than that in PTU group (76.3% vs 58.9%, P < 0.01). CONCLUSIONS: MPO
      antibodies from patients with PTU-induced vasculitis and patients with primary
      MPA could recognize more than one epitopes on native MPO molecule. Although the
      epitopes were overlapping between the two groups, the epitopes of MPO antibodies
      from patients with PTU-induced vasculitis might be more restricted.

PMID- 15730738
TI  - [A clinical and laboratory study of 11 cases of t(6;11)(q27;q23) acute leukemia].
AB  - OBJECTIVE: To analyse the morphologic, immunophenotypic, cytogenetic and clinical
      features of acute leukemia with t(6;11)(q27;q23). METHODS: Cytogenetic
      examination of bone marrow cells was performed with direct method or 24 h culture
      method. R-bands by heating using Giemsa (RHG) banding technique was used for
      karyotype analysis. mixed lineage leukemia (MLL) rearrangement was detected by
      interphase fluorescence in situ hybridization (FISH) using dual-color MLL probe
      in 10 cases. Chromosome painting was performed by using whole chromosome paints 6
      and 11 in 5 cases. RESULTS: t(6;11)(q27;q23) was predominantly found in acute
      myeloid leukemia (AML)-M(5) (8/11 cases). Increased WBC between 10 and 100 x
      10(9)/L was found in 9 cases. Liver, spleen and/or lymph node infiltrations were
      found in 9 cases. t(6;11) as a sole abnormality was detected in 9 cases, However,
      additional aberrations besides t(6;11) were detected in the other two cases. Dual
      color FISH analysis detected the MLL rearrangement in 10 cases. A reciprocal
      translocation between 6 and 11 was proved by chromosome painting technique in 5
      cases. The immunophenotypical analysis of leukemia cells showed co-expressed
      myeloid and lymphocyte antigens in 4 cases. Blast cells were positive for CD(34)
      antigen in 8 patients except case 8. Median survival was 6 months in this series.
      CONCLUSIONS: t(6;11) acute leukemia had unique clinical features and a poor
      prognosis. Chromosome painting technique and dual-color FISH are reliable tools
      for detecting this translocation and MLL rearrangement respectively.

PMID- 15730739
TI  - [A study of subcortical infarcts and leukoencephalopathy (CADASIL) in a family
      with autosomal cerebral dominant arteriopathy].
AB  - OBJECTIVE: To investigate the clinical features, hereditary pattern, neuroimaging
      characteristics and diagnostic method of cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: A
      systematic study on the clinical manifestations, neuroimaging characteristics,
      pathology and molecular genetics was performed. An investigation on the onset and
      hereditary pattern of the family tree of the proband was also done. RESULTS: The
      main clinical features of the proband including history of recurrent ischemic
      stroke, poor memory/cognition or dementia were noted. Fifteen cases pertaining to
      4 generations of the proband with clinical or subclinical onset and confirmed
      classical family history of autosomal dominant hereditary were studied.
      Neuroimaging examination showed subcortical multiinfarct lesions and
      leukoencephalopathy. Electron microscope examination of the skin. Biopsy
      indicated thickening of basement membrane and presence of granular osmiophilic
      material (GOM) in the arterioles. A mutation on the fourth exon of notch 3 gene
      was revealed. Migraine, hypertension, diabetes and risk factors of
      arteriosclerosis were not found. All the features mentioned above in this family
      are in conformity with the diagnostic standard of CADASIL. CONCLUSIONS: It is
      possible to define CADASIL clinically by way of studying the clinical features,
      hereditary pattern, neuroimaging characteristics, skin biopsy and sequencing of
      gene without resorting to brain biopsy.

PMID- 15730758
TI  - [Preliminary exploration on the medical literature in "The 17th volume of great
      canon of Yongle newly discovered overseas"].
AB  - During our exploration on the history of compilation, spread, reprinting of Yong
      le da dian (Great Canon of Yongle) and the analysis made on the materials of
      medicine; history of medicine, and medical literature in the "17th Volume of
      Great Canon of Yongle Newly Discovered Overseas", we found that there are
      materials cited over 10 kinds of literature of the Song, Jin, and Yuan dynasties
      and other fragmentary materials. The academic value of the materials include; for
      the proofreading and collation of available extant medical literature; for the
      supplement of lost medical books or remained medical books; for the exploration
      of new medical historical materials; and for the correction of errors in modern
      tool books in TCM.

PMID- 15730740
TI  - [Human cartilage glycoprotein 39 mRNA expression in peripheral blood and synovium
      mononuclear cells in rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the expression of human cartilage glycoprotein 39 (HC
      gp-39) in peripheral blood mononuclear cells (PBMC) and synovium of rheumatoid
      arthritis (RA) patients. METHODS: Levels of HC gp-39 mRNA were detected by
      reverse transcription-polymerase chain reaction in PBMC of 31 patients with RA, 6
      with osteoarthritis (OA), 10 with spondylarthropathy (SpA), 5 with systemic lupus
      erythematosus (SLE), and of 10 healthy controls. Levels of HC gp-39 mRNA were
      also detected in synovium of 7 patients with RA and 5 with OA. The expression of
      HC gp-39 was semi-quatificated by HC gp-39/tubulin ratio. RESULTS: HC gp-39 mRNA
      expression in PBMC was increased in RA patients (the HC gp-39/tubulin ratio was
      0.8690 +/- 0.5240), compared with OA (P = 0.024), SpA (P = 0.049), SLE (P =
      0.043) and with healthy control subjects (P = 0.033). There were no statistically
      significant differences among OA, SpA, SLE and healthy controls. The level of HC
      gp-39 mRNA expression in RA synovium was also significantly higher than the level
      found in OA (P = 0.04). CONCLUSIONS: HC gp-39 mRNA was obviously overrepresented
      in RA patients PBMC and synovium. These data support a possible pathogenic role
      of HC gp-39, as a candidate autoantigen, in the autoimmune response of RA.

PMID- 15730759
TI  - [Investigation on "gout" and comparison of disorder between Chinese and Western
      medicine in pre-Song-yuan dynasty].
AB  - Before the Song-Yuan dynasties, it was claimed that "gout" is the result of heat
      in the blood plus invasion of wind, cold, or dampness, leading to coagulation of
      turbid dampness in the channel-collaterals, characterized by arthralgia,
      exacerbated in the nighttime. "Gout" was first seen in the Ming yi bie lu (Other
      Records of Famous Physicians) of the Liang dynasty. Before that, it was
      categorized under "bi" syndrome. No detailed description was given to "gout"
      during the period from the first appearance of the title "gout" to the Yuan
      dynasty. In fact, it was vaguely mentioned in "bi", "li jie", and "bai hu (white
      tiger)" disorders. The title of "gout" was named by Zhu Danxi, and appeared
      alternately with gouty arthritis. "li jie" and "bai hu" are titles of two
      different diseases which were jointly called "lijiebaihu" in the Song dynasty,
      both similar to gouty arthritis. The TCM title of gout was based on this
      condition which is specific and very proximate to gouty arthritis.

PMID- 15730760
TI  - [Liu Yuduo, the first medical officer of the Qing dynasty].
AB  - Liu Yuduo was a royal physician with proficient medical techniques and was
      trusted by the royal family. He was praised as the "First medical officer" by
      Yongzheng emperor. With Wu Qian, he was the co-compiling officer of the Yi zong
      jin jian (Golden Mirror of Medicine) during the Qianlong reign and made immortal
      contributions to the development of traditional Chinese medicine (TCM). There
      were scanty materials about Liu in TCM literature and orthodox history in later
      ages. However, much materials about him can be found in archives, memorials to
      the emperors. Emperors' instructions, or even local annals which provide much
      materials to the research of Liu Yuduo.

PMID- 15730761
TI  - [History of "rang", an ancient disease entity].
AB  - The title of "rang" was first appeared in Shi You's Ji jiu pian in which there is
      a sentence saying that "thirst, vomiting, nausea, coughing, panting, and rang".
      It refers to dysentery. Later, many other derivatives, including "rang
      dysentery", "niang dysentery" and "niang du dysentery" etc. appeared. "Rang li"
      refers to chronic dysentery; "niang li" and "niang du li" refer to stagnation
      resulting in mass formation. All these titles are of the same definition, viz.
      referring to the development of "rang", or dysentery. However, careful analysis
      may also reveal different meanings, but without clear demarcation. They can be
      applied for the same disorders.

PMID- 15730762
TI  - [Investigation on the title of bu mei (sleepless)].
AB  - There are various titles applied for "sleepless", including mu bu ming (unclosed
      eyes), bu de mian (unable to sleep), bu de wo (unable to lie down), shi mian
      (insomnia). The implications of the titles vary according to different periods.
      Bu de wo (unable to lie down) was first appeared in Zu bi shi yi mai jiu jing
      (Moxibustion Classic of Foot and Arm Eleven Channels) and Yin yang shi yi mai jiu
      jing (Moxibustion Classic of Yin-Yang Eleven Channels), while bu de wo, mu bu
      ming, and ye bu mei were appeared in Huang di nei jing (Inner Canon of Yellow
      Emperor), bu mei was first seen in Nan jing (Classic of Questioning). When bu de
      mian and bu de wo were applied in Zhang Zhongjing's Shang han lun (Treatise on
      Cold Pathogenic Diseases) and Jin kui yao lue (Synopsis of Golden Chamber), it
      exerted good influence in later generations. The title of bu mei was more popular
      after the Ming and Qing dynasties. This titles is the most appropriate one from
      the standpoint of syndrome itself as viewed from its semantic implication and its
      accuracy.

PMID- 15730763
TI  - [The archaic pronunciation of materia medica from Central Plains in the Han
      dynasty retained in Chinese medicinal business in Taiwan].
AB  - Chinese traditional medicine took its root in Taiwan together with the culture of
      Central Plains since our ancestors traveled to Taiwan during the turn of the Ming
      Qing dynasties. For 400 years, the profession of Chinese medicine continues to
      develop through the transmission from fathers to sons, from tutors to disciples.
      During our contacts with Chinese medicinal businessmen, we found that this
      routinely closed and time-honored profession retained the archaic pronunciation
      of materia medica from Central Plains in the Han dynasty. This is a living
      database for studying ancient Chinese language.

PMID- 15730764
TI  - [On Mackenzie, a missionary of the London Mission].
AB  - Mackenzie, a missionary of the London Mission, came to China in 1875. He first
      did missionary works in Hankou and moved to Tianjin in 1879, during which he
      established the London Mission Hospital and a medical school under the assistance
      of Li Hongzhang. He made certain contributions to the elimination of diseases in
      Chinese people and the spread of western medicine.

PMID- 15730765
TI  - [Sackett [correction of Sacker], a pioneer of clinical epidemiology and evidence
      based medicine].
AB  - Sacker, a world famous clinical epidemiologist and pioneer of evidence-based
      medicine, to which he makes great contributions to its appearance and
      development. He is an outstanding doctor and medical researcher, director of all
      internal medicine, and an even more famous educationist of clinical epidemiology.
      He has his own living philosophy, and is indefatigable and conscientious to his
      profession.

PMID- 15730766
TI  - [Analysis on origin and evolution of mumps].
AB  - There was a preliminary recognition on mumps during the Qin-Han to Sui-Tang
      dynasty, laying a foundation for the scholastic development on this topic in
      later generations. The title of this disease was identified in Song-Jin-Yuan
      dynasty with gradual deepening on its principle-method-formula-medication system,
      a great progress of recognition as compared with the previous ages. In the Ming
      Qing dynasty, the recognition became even more systematic, with certain
      breakthrough in the system of principle-method-formula-medication. In modern age,
      the experiences were inherited and developed to integrate to modern biomedicine,
      so that the theory and clinical practice become even more perfect.

PMID- 15730775
TI  - [The prospect of application research on Mycobacteriophages].

PMID- 15730776
TI  - [Study on the method for rapid detection of Mycobacterium tuberculosis by phage
      amplified biologically assay].
AB  - OBJECTIVE: To set up a method for rapid detection of Mycobacterium tuberculosis
      (MTB) by phage amplified biologically (PhaB) assay and to investigate the optimal
      test condition. METHODS: Various test conditions were compared in order to
      observe the influence on detective results after MTB was infected by
      Mycobacteriophage. The test condition established was used for detection of
      sputum samples, and the results were compared with BIOTEC Lab test. RESULTS: The
      bacterial concentration of MTB in 200 - 500/ml was detected by PhaB assay at 1 x
      10(9) plaque forming unite (PFU)/ml of Mycobacteriophage, 37 degrees C for 60
      min. The optimal concentration of virucidal for inactivation of Mycobacteriophage
      was 100 mmol/ml for 5 min at room temperature. The bacteriolytic plaque was clear
      at the concentration of 1 x 10(8)/ml indicator cells. Bacterium inactivated by
      heat can not be infected by Mycobacteriophage. Positive result was observed for
      control strains of H(37)Rv, H(37)Ra and M. bovis while negative result was
      obtained for 7 strains of non-Mycobacterium and 16 control strains of non
      Tuberculosis Mycobacteria (NTM). The 4 strains of NTM (M. fortuitum, M.
      intrcellulare, M. aurum, M. phlei) showed positive reaction at higher
      concentrations (> 1 x 10(5)/ml). The repetition test showed that the
      differentiation coefficient in batch and inner was all under 15%. There was a
      significantly difference (P < 0.01) in positive rate between two digestion
      decontamination procedure with N-acetyl-cysteine-NaOH liquefacient (94%) and NaOH
      liquefacient (62%). The positive rate of the samples cultured one day (65%) was
      significantly higher than that of the samples without preculture (40%). The
      results for detection of clinical samples by two reagents, ours and BIOTEC Lab,
      were nearly the same. CONCLUSION: Because its rapidity, simplicity, and
      sensitivity, PhaB assay can be used for rapid detection of MTB, but the condition
      of test is very important.

PMID- 15730777
TI  - [A study of standardization to the rapid detection of Mycobacterium tuberculosis
      based on phage amplified biologically assay].
AB  - OBJECTIVE: To evaluate the phage amplified biologically (PhaB) assay in the rapid
      detection of Mycobacteria tuberculosis in samples. METHODS: The conditions of the
      PhaB assay, including various infection times prior to addition of virucide and
      the effect of the inactivation agents which could inactive the extracellular
      phages, were investigated and compared. The sensitivity, specificity and accuracy
      of PhaB assay were tested when it was used in rapid detection of Mycobacterium
      tuberculosis. Some agents of the method, including Mycobacteriophage, virucide
      and help cells (Mycobacterium smegmatis) were investigated at different times
      when they were preserved at 4 degrees C. RESULTS: (1) The optimal infection time
      prior to addition of virucide was between 3 and 4 hours. Four percent FAS
      (ferrous ammonium sulphate) could inactive 1 x 10(9) PFU (plaque-forming unit) in
      five minutes. (2) The samples were positive when 80 - 200 CFU of Mycobacterium
      tuberculosis were present. However, the positive rate of non-Tuberculosis
      Mycobateria (NTM) was varied. All bacteria lived in the respiratory tract were
      negative. (3) The important agents used in this test showed optical effect when
      they were preserved at 4 degrees C. CONCLUSIONS: The method based on
      mycobacteriophage-amplified biologically assay could rapidly detect Mycobacterium
      tuberculosis, and it was effective, accurate, and simple to perform. It was
      appropriate for using in developing countries, compared with a variety of
      molecular techniques.

PMID- 15730778
TI  - [Application of rapid detection for rifampin resistance in clinical isolates of
      Mycobacterium tuberculosis by phage amplified biologically assay].
AB  - OBJECTIVE: To set up a rapid detection method for rifampin susceptibility with
      phage amplified biologically (PhaB) assay and to evaluates its value in the
      detection of rifampin resistance in clinical isolates of Mycobacterium
      tuberculosis. METHODS: The assay was established to detect rifampin resistance in
      524 clinical isolates of Mycobacterium tuberculosis, and the result was compared
      to that of the absolute concentration method. The minimum inhibitory
      concentration (MIC) was detected by BACTEC MGIT 960 method for the discrepant
      isolates. RESULTS: Rifampin susceptibility results were available for 524 strains
      of Mycobacterium tuberculosis. A total of 223 strains were found to be rifampin
      resistant and 301 strains were rifampin susceptible detected by PhaB assay, but
      211 and 313 strains were respectively found to be rifampin resistant and
      susceptible by conventional methods. There were 198 and 288 rifampin resistant
      and susceptible strains both detected by the two methods. The drug susceptibility
      of 35 strains was the same in 38 discrepant isolates by the PhaB assay and
      absolute concentration method. The sensitivity, specificity, positive and
      negative predictive values as well as the overall accuracy for the PhaB assay was
      93.8%, 92.0%, 88.8%, 95.7% and 92.7% respectively if the judgment standard was
      adopted by conventional methods. CONCLUSION: The result of PhaB assay was
      available within 2 days. This method, which is simple and does not need special
      equipment, can be used for rapid screening for rifampin resistance from
      Mycobacterium tuberculosis.

PMID- 15730780
TI  - [Analysis and evaluation of phage amplified biologically assay, DNA sequencing
      analysis and single-strand conformational polymorphism for the drug
      susceptibility testing of Mycobacterium tuberculosis].
AB  - OBJECTIVE: To rapidly identify drug-resistant Mycobacterium tuberculosis using
      phenotypic and genotypic methods and to evaluate the clinical significance of
      rapid phenotypic susceptibility test by phage amplified biologically assay
      (PhaB). METHODS: PhaB, DNA sequencing and polymerase chain reaction-single strand
      conformational polymorphism (PCR-SSCP) were performed on the 91 rifampicin (RFP)
      resistant strains (including 82 multi-drug resistant Mycobacterium tuberculosis
      strains), 42 RFP-susceptible strains, 75 ofloxacin (OFLX)-resistant strains and
      40 OFLX-susceptible strains at the same time. RESULTS: The results obtained using
      PhaB assay, DNA sequencing and PCR-SSCP were compared with the absolute
      concentration method. For RFP susceptibility, the accordance, sensitivity and
      specificity of PhaB were 93%, 92% and 95% respectively; the accordance,
      sensitivity and specificity of DNA sequencing were 93%, 90% and 100%
      respectively; those of PCR-SSCP were 90%, 86% and 100% respectively. For OFLX
      susceptibility, the accordance, sensitivity and specificity of PhaB assay were
      95%, 95% and 95%; those of DNA sequencing were 80%, 71% and 98% respectively;
      those of PCR-SSCP were 75%, 63% and 98% respectively. CONCLUSIONS: PhaB assay is
      a low-cost, rapid, and sensitive method and shows high accordance with absolute
      concentration technology. It can give drug susceptibility test results within 48 
      96 h, and is a promising technology in clinical laboratory.

PMID- 15730781
TI  - [Clinical investigation of the first case of severe acute respiratory syndrome in
      Beijing in 2004].
AB  - OBJECTIVE: To summarize and analyze the clinical manifestation of the first case
      of severe acute respiratory syndrome (SARS) in Beijing in 2004, and therefore
      providing clues of differential diagnosis for physicians to diagnose SARS cases
      in a timely manner and find out its transmission. METHODS: The clinical data of
      an out-hospital-imported SARS case and its clinical features were analyzed.
      RESULTS: (1) The delay in diagnosis of this SARS case was largely associated with
      unclear epidemiologic history; (2) The SARS patient showed characteristics of
      typical pneumonia in the early stage. The numbers of peripheral white blood cells
      and lymphocytes were in the normal range without any specific changes typical of
      SARS. CONCLUSION: It is very important for physicians to be alert to the
      epidemiological data for an early diagnosis of SARS, and therefore early
      isolation and initiation of appropriate treatment.

PMID- 15730782
TI  - [Autoantibody against granulocyte-macrophage colony-stimulating factor and other
      serum markers in pulmonary alveolar proteinosis].
AB  - OBJECTIVE: To evaluate the application of serum markers in the diagnosis,
      monitoring and understanding of the mechanisms of pulmonary alveolar proteinosis
      (PAP), the levels of the autoantibody against granulocyte-macrophage colony
      stimulating factor (anti-GM-CSF antibody), granulocyte-macrophage colony
      stimulating factor (GM-CSF), and other serum markers, lactate dehydrogenase (LDH)
      and carcinoembryonic antigen (CEA), were measured in patients with PAP. METHODS:
      Serum samples were taken from 17 PAP patients (16 idiopathic and 1 congenital
      PAP), 18 patients with other pulmonary diseases disease control) and 40 healthy
      volunteers (healthy control). Anti-GM-CSF antibody was measured with indirect
      enzyme-linked immunosorbent assay (ELISA). GM-CSF and CEA were measured with
      commercial ELISA kits. LDH was measured with a kinetic method. RESULTS: The
      absorbance at 450 nm of serum anti-GM-CSF antibody in the idiopathic PAP (I-PAP),
      disease control and healthy control were 1.263 +/- 0.047, 0.835 +/- 0.018 and
      0.246 +/- 0.009 respectively. The sensitivity and specificity of anti-GM-CSF in
      the diagnosis of I-PAP were 93.8% and 100% respectively, if the cutpoint was set
      as 4 times the average value of the healthy control. GM-CSF was not detectable in
      most PAP and other samples except 3/17 of PAP and 1/19 of disease control. The
      serum level of LDH was increased in I-PAP patients and correlated with CEA (r =
      0.518) and alveolar-artery oxygen gradient (r = 0.769). CEA was increased in I
      PAP patients [(12.85 +/- 3.79) ng/ml] compared with disease control [(2.04 +/-
      0.63) ng/ml] and health control [(1.46 +/- 0.34) ng/ml] and correlated with
      alveolar-artery oxygen gradient (r = 0.552). The LDH levels decreased after
      lavage therapy [(348.38 +/- 38.88), (242.88 +/- 30.71) U/L, P < 0.05].
      CONCLUSIONS: The high sensitivity and specificity of anti-GM-CSF antibody make it
      a potential diagnostic serum marker for I-PAP. LDH and CEA are useful markers in
      evaluation of disease progression of PAP.

PMID- 15730783
TI  - [Application of multi-predictors in the ventilator weaning process].
AB  - OBJECTIVE: To evaluate the effects of rapid shallow breathing index (RSBI),
      airway occlusion pressure (P(0.1)) and traditional weaning predictors in the
      weaning process for patients undergoing prolonged mechanical ventilation.
      METHODS: Having past 60-min spontaneous breathing trial and satisfied at least 8
      of 10 traditional weaning predictors, 80 patients fulfilled the criteria of
      discontinuing ventilation and were included in the study. The coordinate
      capability of breath movement, the quantity of sputum, the quantity of rales in
      the lungs, the efficiency of coughing, respiratory rate, tidal volume, minute
      ventilation, compliance of the respiratory system, pulse oxygen saturation, pH
      value of the arterial blood, RSBI and P(0.1) were determined. According to the
      outcome of weaning from mechanical ventilation, patients were divided into a
      failure group and a success group. T test, chi-square test and Logistic
      regression analysis were used for statistics analysis. RESULTS: Sixteen (20%)
      patients failed weaning. By univariate analysis, the average age, RSBI and P(0.1)
      values were significantly different between the failure and the success groups (P
      < 0.05). Logistic regression analysis with weaning outcome as the dependent
      variable, RSBI [(71 +/- 23) breaths.min(-1).L(-1), (53 +/- 13) breaths.min(-1).L(
      1), OR = 1.03] and P(0.1) [(7.4 +/- 2.1) cm H2O, (3.6 +/- 1.4) cm H2O, OR = 6.87]
      were the only significant variables in the model. Using RSBI </= 105 breaths.min(
      1).L(-1) as the threshold value for predicting successful weaning, the
      sensitivity, specificity and accuracy were 90%, 36% and 78% respectively. Using
      P(0.1) </= 4.5 cm H2O as the threshold value for predicting successful weaning,
      the sensitivity, specificity and accuracy were 87%, 66% and 82% respectively. The
      values of ten traditional predictors, as spirometric and gas exchange, showed no
      significant difference between the two groups. CONCLUSIONS: In the weaning
      process for patients undergoing prolonged mechanical ventilation, RSBI and P(0.1)
      are valuable and accurate predictors. Traditional weaning predictors may be
      useless.

PMID- 15730784
TI  - [Effect of ligustrazine on airway remodeling in asthmatic rats].
AB  - OBJECTIVE: To observe the effect and mechanism of ligustrazine on the airway
      remodeling. METHODS: Thirty-two SD rats were randomly divided into 4 groups: the
      normal group (A), the model group (B), the ligustrazine low-dose group (C, 40
      mg/kg) and the ligustrazine high-dose group (D, 80 mg/kg), with 8 rats in each
      group. The chronic asthmatic model was established by repeated inhalation of
      ovalbumin. The changes of collagen and transforming growth factor-beta(1) (TGF
      beta(1)) contents in the airway wall, the thickness of smooth muscle and basement
      membrane, inner and outer diameter were measured by the computerized image
      analysis system. RESULTS: The thickness of smooth muscle and basement membrane
      were (11.3 +/- 1.3, 11.3 +/- 1.7) microm in D group, (19.7 +/- 1.8, 19.8 +/- 1.6)
      microm in B group, the difference being significant (P < 0.01), as compared with
      A group [(10.6 +/- 1.2) microm, (9.8 +/- 1.6) microm] and C group [(11.6 +/- 0.9)
      microm, (12.3 +/- 1.8) microm], the difference being not significant (all P >
      0.05). The difference in the ratio of inner diameter to outer diameter was
      significant between D group (0.77 +/- 0.06) and B group (0.63 +/- 0.05), P <
      0.01. The contents of collagen type III and TGF-beta(1) were (21 +/- 5, 26 +/- 5)
      in D group, (55 +/- 7, 69 +/- 14) in B group, the difference being significant (P
      < 0.01). The differences were also significant when C group [32 +/- 8, 38 +/- 10]
      was compared with D group (P < 0.05) and B group (P < 0.01). The contents of
      collagen type I showed no difference among the 4 groups (A group: 34 +/- 13, B
      group: 44 +/- 8, C group: 36 +/- 8, D group: 39 +/- 8; all P > 0.05). A close
      correlation between TGF-beta(1) and collagen type III was demonstrated (r = 0.844
      2, P < 0.01). CONCLUSION: Ligustrazine might suppress airway remodeling by
      decreasing the expression of TGF-beta(1) and reducing deposition of collagen.

PMID- 15730785
TI  - [Effects of interleukin-13 on the gob-5 and MUC5AC expression in lungs of a
      murine asthmatic model].
AB  - OBJECTIVE: To study the influence of interleukin-13 (IL-13) on the gob-5, a
      member of Ca(2+)-activated Cl(-) channel and mucin gene MUC5AC expression in
      lungs of a murine asthmatic model, and to investigate their effects on the
      pathogenesis of asthma. METHODS: Forty-five male BALB/c mice were randomly
      divided into a control group, an asthmatic group and an IL-13 group. Expression
      of gob-5 mRNA, MUC5AC mRNA and MUC5AC protein in the lungs were detected by
      reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical
      assay respectively. RESULTS: No gob-5 mRNA expression in the lung was detected in
      the control group, while it was positive in the asthmatic group. The gob-5 mRNA
      in the lung of the IL-13 group and the asthmatic group was 1.246 +/- 0.008 and
      1.136 +/- 0.007 respectively (P < 0.01). In the asthmatic group, both MUC5AC mRNA
      (0.161 +/- 0.011) and protein expression (7 mice positive) increased compared
      with the control group (0.070 +/- 0.004 and 2 mice positive, respectively) (P <
      0.01 and 0.05, respectively). IL-13 increased the expression of MUC5AC mRNA
      (0.250 +/- 0.014) and protein (13 mice positive) in the lung of the asthmatic
      group, and there was a significant difference between the IL-13 group and either
      the control group (0.070 +/- 0.004 and 2 mice positive, respectively) or the
      asthmatic group (0.161 +/- 0.011 and 7 mice positive, respectively, all P <
      0.05). There was a significant association between gob-5 mRNA expression and
      MUC5AC mRNA expression in both the IL-13 group and the asthmatic group (r = 0.986
      and 0.961, respectively, both P < 0.05). CONCLUSION: IL-13 is a critical cytokine
      in the pathogenesis of asthma, and gob-5 may be one of the important genes in
      inducing airway mucus overproduction of asthma.

PMID- 15730787
TI  - [Evaluation of a simplified maintenance of wakefulness test for the diagnosis of
      daytime sleepiness].
AB  - OBJECTIVE: The purpose of this study was to assess a simplified maintenance of
      wakefulness test (Oxford SLEep Resistance test, OSLER test) in evaluating
      excessive daytime sleepiness. METHODS: Seventy-four snorers with or without
      obstructive sleep apnea-hypopnea syndrome (OSAHS) were studied. Two OSLER tests
      were performed in the afternoon with a gap of 30 minutes. Epworth sleepiness
      scale (ESS) was also recorded. An overnight sleep study using a multi-channel
      system was performed to distinguish nonapneic snorers (snorer group, n = 43) from
      OSAHS patients (OSAHS group, n = 31). The OSLER test was repeated in the OSAHS
      group after two month treatment with nasal continuous positive airway pressure
      (CPAP). RESULTS: There was a significant difference in sleep latency measured by
      the OSLER test between the OSAHS group and the snorer group (16.03 +/- 12.27 vs
      25.70 +/- 14.62, P < 0.01). A significant correlation was found between sleep
      latency and ESS (r = -0.45, P < 0.01). Twenty-five of the 31 patients in the
      OSAHS group were treated with CPAP for two months. Sleep latency increased from
      16.20 +/- 12.98 to 36.38 +/- 21.10 after treatment (P < 0.01). CONCLUSION: The
      OSLER test appears useful in assessing excessive daytime sleepiness.

PMID- 15730786
TI  - [Effect of potassium channel on the proliferation, apoptosis and related-gene
      expression in human bronchial smooth muscle cells].
AB  - OBJECTIVE: To investigate the effects of three potassium channels, voltage
      dependent K(+) channel (K(V)), calcium-activated K(+) channel (K(Ca)) and ATP
      sensitive K(+) channel (K(ATP)), on the proliferation, apoptosis and related-gene
      expression in human bronchial smooth muscle cells (HBSMCs). METHODS: Normal human
      bronchial tissues were obtained from 5 patients undergoing lung partial resection
      for carcinomas. The cultured HBSMCs were divided into four groups: (1) control
      group; (2) 4-aminopyridine (4-AP) group: containing 4 mmol/L 4-AP; (3) TEA group:
      containing 1 mmol/L TEA; (4) Glib group: containing 0.1 mmol/L Glib. The cell
      cycles were observed by flow-cytometry; Ca(2+) concentration in HBSMCs were
      investigated by fluorescent quantification using fluorospectrophotometer. The
      proliferation and apoptosis were detected by MTT methods and TUNEL, respectively.
      Immunocytochemical staining was used to detect the effects of three potassium
      channel blockers on the expressions of PCNA and apoptosis related-gene Fas, FasL
      of HBSMCs. RESULTS: (1) The K(V) blocker 4-AP was shown to significantly increase
      the optical density value [the value of A of the 4-AP group was (0.67 +/- 0.14),
      compared to the control group (0.30 +/- 0.08), P< 0.01] and the expression of
      proliferating cell nucleus antigen [the positive percentage of PCNA of the 4-AP
      group was (89 +/- 7)%, compared to the control group (23 +/- 5)]%, P < 0.01). 4
      AP significantly increased the Ca(2+) concentration [(255 +/- 17) nmol/L] in
      cultured HBSMCs, compared to the control group [(98 +/- 7) nmol/L, P < 0.01] and
      the numbers [(28.8 +/- 2.4)%] of S + G(2)M HBSMCs by flow-cytometry in cultured
      HBSMCs, compared to the control group [(12.6 +/- 4.8)%, P < 0.01]. The value of A
      of TEA group and Glib group were all (0.30 +/- 0.07). The positive percentage of
      PCNA of the two groups were (21 +/- 5)%, (20 +/- 4)%, respectively. Ca(2+)
      concentration of the two groups were (97 +/- 7) nmol/L, (99 +/- 6) nmol/L,
      respectively. And the numbers of S + G(2)M HBSMCs were (12.8 +/- 4.4)%, (11.0 +/-
      4.4)%, respectively. But no significant differences were found between the two
      groups and the control group (all P > 0.05). (2) The level of TUNEL and the
      expressions of Fas and FasL of the control were (4.36 +/- 0.66)%, (2.92 +/-
      0.25)%, (4.0 +/- 0.6)%, respectively. 4-AP significantly decrease the apoptosis
      rate and the expressions of Fas, FasL [(0.84 +/- 0.13)%, (0.92 +/- 0.16)]%, (1.4
      +/- 0.6)%, respectively) (compared to control, all P < 0.01). The level of TUNEL
      of TEA group and Glib group were (4.47 +/- 0.93)%, (4.33 +/- 0.77)%,
      respectively. And the expressions of Fas, FasL of the two groups were (2.87 +/-
      0.23)%, (4.2 +/- 0.8)%, (2.91 +/- 0.26)% and (4.2 +/- 0.9)%, respectively. There
      were no significant differences between the two groups and the control group (all
      P > 0.05). CONCLUSION: Inhibition of K(V) activity can increase the proliferation
      and intracellular [Ca(2+)]i, and decrease the apoptosis of HBSMCs, but inhibition
      of K(Ca) and K(ATP) showed no effects.

PMID- 15730798
TI  - [Launching and promoting an aggressive three-stage rehabilitation therapy on
      acute cerebrovascular diseases].

PMID- 15730788
TI  - [Phage amplified biologically assay and its application in rapid detection of
      Mycobacterium tuberculosis].

PMID- 15730799
TI  - [Measurement and treatment of human immunodeficiency virus infection].

PMID- 15730800
TI  - [Study of post-stroke dementia].

PMID- 15730801
TI  - [Prevention and control of serious communicable diseases in China].

PMID- 15730802
TI  - [Effects of three-stage rehabilitation treatment on acute cerebrovascular
      diseases: a prospective, randomized, controlled, multicenter study].
AB  - OBJECTIVE: To evaluate the effect of tertiary rehabilitation treatment on acute
      cerebrovascular diseases. METHODS: Fifteen tertiary rehabilitation networks were
      set up throughout the country. 1078 patients with acute cerebrovascular diseases
      were randomly divided into 2 groups: rehabilitation group and control group, out
      of which 19 patients died, 157 dropped out, and 7 successive evaluations were
      completed in 902 patients that. 439 of the remaining 902 patients in the
      rehabilitation group, 266 males and 173 females, aged 61 +/- 11, 278 cases with
      cerebral infarction and 161 with cerebral hemorrhage, received routine treatment
      and early rehabilitation for 28 days in the ward of neurology, and then went home
      and received community rehabilitation for 6 months or underwent specialized
      reinforcement training for 2 months and after that went home and received
      community rehabilitation for 4 months. The 463 patients in the control group, 281
      males and 182 females, aged 60 +/- 11, 291 of which with cerebral infarction and
      172 with cerebral hemorrhage, received only routine treatment and early
      rehabilitation for 28 days in the ward of neurology, and then went home to
      conduct rehabilitation training by themselves or their family members for 6
      months. Evaluation was conducted 7 times, with National Institutes of Health
      Stroke Scale (NIHSS), Fugl-Meyer motor function scale, Barthel index, SF-36
      scale, Lowenstein occupational therapy cognitive assessment (LOTCA), Westen
      aphasia battery, Hamilton depression scale, and modified Ashworth spasm scale,
      one week after the onset and by the ends of 1, 2, 3, 4, 5, and 6 months after the
      onset respectively. RESULTS: The scores of clinical neurological impairment, Fugl
      Meyer scores, SF-36 scores, incidence of PSD, and modified Ashworth scores (for
      upper and lower limbs) were lower, and LOTCA scores and Barthel indexes were
      higher at different time points in the rehabilitation group than in the control
      group; and the differences were statistically significant since the 2nd month
      after the onset. By the end of the 6th month, the patients of the rehabilitation
      group basically re-achieved the ability of self-care in daily activities with a
      Barthel index of 84 +/- 33. The patients of the control group also recovered to a
      certain degree, however, to a smaller extent in comparison with the
      rehabilitation group. CONCLUSION: Tertiary rehabilitation treatment of
      cerebrovascular diseases is effective in improving motor function, ability of
      daily living activities, and quality of life and reducing the incidence rates of
      secondary complications.

PMID- 15730803
TI  - [Effects of standardized three-stage rehabilitation on recovery of neurological
      function in stroke patients with hemiplegia].
AB  - OBJECTIVE: To explore the effects of standardized three stages' rehabilitation on
      the neurological function in stroke patients with hemiplegia. METHODS: All 52
      patients firstly are brought into two blocks: primary cerebral infarction and
      primary cerebral hemorrhage then are divided into treated group and controlled
      group randomly. Patients in the treated group are given Standardized Three
      Stages' Rehabilitation, while those in the controlled group are only given normal
      internal medicine treatments that are the same as the treated group but without
      Standardized Three Stages' Rehabilitation. All patients would be assessed with
      the scale of Clinical Neurological Function Defects (CNFD) at the entering time,
      the end of 1st month, 3rd month and 6th month respectively after stroke. RESULTS:
      The scores of the treated group are lower than those of the controlled group (P <
      0.001) at every stage, the margins between every stage's scores in the treated
      group are greater than those in the controlled group (P < 0.001). The scores of
      the treated group's patients are about 51%, 34%, 18% and 8% of total scores at
      the entering time, the end of 1st month, 3rd month and 6th month after stroke
      differently, but that of the controlled group are about 58%, 54%, 42% and 37% of
      total scores differently. The margins between the scores of entering time and
      that of the end of 1st month, 3rd month and 6th month in the treated group are
      17%, 33% and 43% of total scores respectively, but that of the controlled group
      are about 5%, 16% and 21% of total scores differently. CONCLUSION: Standardized
      three stages' rehabilitation could promote stroke patients' motor function of
      every stage obviously.

PMID- 15730804
TI  - [Correlation of thrombospondin-1 G1678A polymorphism to stroke: a study in
      Chinese population].
AB  - OBJECTIVE: To assess whether thrombospondin-1 (THBS-1) gene G1678A polymorphism
      is associated with stroke. METHODS: Samples of venous blood were collected from
      1634 patients with stroke, including cerebral thrombosis, lacunar cerebral
      infarction, and cerebral hemorrhage confirmed by CT or MRI, and sex-, and age
      matched 1171 controls without cerebrovascular diseases. Genotypes were determined
      with polymerase chain reaction and allele-specific restriction enzyme analysis.
      RESULTS: The frequency of the THBS-1 gene 1678 AA genotype (0.503 vs. 0.441) was
      significantly higher in the cerebral thrombosis group than in the controls (P =
      0.008). The frequency of the G allele (0.299 vs. 0.339) was significantly lower
      in the cerebral thrombosis group than in the controls (P = 0.009). No significant
      difference was seen in THBS-1 gene 1678 AA polymorphism either between the
      lacunar cerebral infarction group and the control group or between the cerebral
      hemorrhage group and the control group (all P > 0.05). Multiple logistic
      regression analysis showed that the AA genotype of THBS-1 gene G1678A carriers
      had a higher risk of cerebral thrombosis (OR: 1.4; 95% CI 1.083 - 1.693; P =
      0.008) after adjustment for age, sex, SBP, DBP, BMI, smoking, TC, TG, HDL-C, LDL
      C and Glu. CONCLUSION: AA genotypes in THBS-1 gene G1678A polymorphism may be a
      genetic risk factor of cerebral thrombosis in Chinese population.

PMID- 15730805
TI  - [Study on the DNA damage and repair of peripheral mononuclear leukocytes in
      cerebral ischemic stroke].

PMID- 15730806
TI  - [Effects of epidermal growth factor on the movement and differentiation of neural
      stem cells of subventricular zone in cerebral infarction rats].

PMID- 15730807
TI  - [Biological characteristics of HIV-1 isolates circulating in China are linked to
      its env V3 loop sequence variability].
AB  - OBJECTIVE: To investigate the biological characteristics of the HIV-1 isolates
      circulating in China and to define the association of these properties with env
      V3 loop sequence variability. METHODS: Primary viruses were isolated from fresh
      peripheral blood mononuclear cells (PBMCs) using the traditional co-culture
      method and their capacity of inducing syncytium was tested in MT-2 cells;
      meanwhile, their coreceptor usage was determined with GHOST-cell lines which
      stably express CD4 and the chemokine receptor CCR5 or CXCR4. Furthermore, HIV-1
      V3 and its flanking region sequences were amplified by nest-polymerase chain
      reaction (nest-PCR) and sequenced. A GCG software was used to translate the DNA
      sequences into polypeptide sequences. RESULTS: Five primary viral strains were
      isolated from 3 different regions in China. The isolates LTG0213 and LTG0214
      induced syncytia in MT-2 cells and used CXCR4 as coreceptor. The isolates
      XJN0021, XJN0091, and SHXDC0041 did not induce syncytia and used CCR5 as
      coreceptor. There were obvious differences between X4/SI and R5/NSI viruses in
      env V3 loop sequences. A consensus motif at the positions 8, 11, 18, and 25 in V3
      loop was identified as follows: a sequence as "8-TXXS/GXXXXXXR/QXXXXXXE/D-25"
      will predict the usage of CCR5 coreceptor; a sequence replacing these positions
      with basic amino acids (except position 25) will very likely predict the usage of
      CXCR4 coreceptor. CONCLUSION: The biological characteristics of HIV isolates are
      linked to env V3 loop sequence variability: introducing basic amino acids (or
      translating from acidic amino acids into neutral amino acids) at the positions 8,
      11, 18, and 25 in V3 loop will change viral strain's biological phenotype from
      NSI/CCR5 to SI/CXCR4. The biological phenotype of HIV-1 can be predicted with V3
      loop sequence analysis.

PMID- 15730808
TI  - [HIV-1 nef specific cytotoxic T lymphocyte responses in long-term nonprogressors
      and AIDS patients].
AB  - OBJECTIVE: To investigate the HIV-1 nef specific CD8(+) T cell responses in long
      term nonprogressor (LTNP) and AIDS patient in China. METHODS: Peripheral blood
      mononuclear cells were collected from 7 LTNPs and 9 AIDS patients, 12 males and 4
      females, aged 37 (27 approximately 55). A panel of 26 overlapping peptides
      spanning HIV-1 nef constituting 3 peptide pools was used as antigens. The HIV-1
      nef specific CD8(+) T cell responses of the LTNPs and AIDS patients were examined
      by IFN- ELISPOT assay. The amount of CD4(+) T cell and viral load were detected.
      The relationships between HIV-1 nef specific CD8(+) T cell responses and CD4(+) T
      cell counts and viral loads were studied. RESULTS: The strength of HIV-1 nef
      specific CD8(+) T cell responses of LTNP group was 404 +/- 33 SFC/10(6) PBMCs,
      significantly higher than that of the AIDS group (59 +/- 121 SFC/10(6) PBMCs).
      The strength of HIV-1 nef specific CD8(+) T cell responses was positively
      correlated with the CD4(+) T cell count. No relationship between the strength of
      CD8(+) T cell responses and viral load was found. CONCLUSION: HIV-1 nef specific
      CD8(+) T cell responses may play an important role in preventing disease
      progression of HIV infection. There is a cross immune response between the major
      HIV-1 strains in Europe and those in China.

PMID- 15730809
TI  - [Expression of Survivin in transitional cell carcinoma of urinary bladder and its
      clinical significance].
AB  - OBJECTIVE: Survivin is a member of the inhibitors of apoptosis protein (IAP)
      family. Recent researches had shown that survivin plays an important role in
      oncogenesis. This study was designed to investigate the expression of survivin in
      transitional cell carcinoma (TCC) of urinary bladder and its clinical
      significance. METHODS: Immunohistochemical assay was used to detect the
      expression of survivin in 75 cases of tumor tissue and 7 cases of normal bladder
      tissue. RESULTS: The expression rates of survivin were 77.3% (58/75) in TCC of
      urinary bladder, whereas no expression of survivin was detected in the 7 cases of
      normal bladder tissue. CONCLUSIONS: Expression of survivin protein was observed
      in the tumor tissue derived from the patients with bladder TCC, indicating that
      this protein may play an important rule in carcinogenesis of human urinary
      bladder. The expression of survivin was statistically significant associated with
      tumor grade. Our results suggested that the expression of survivin may be
      considered as a prognostic factor for bladder TCC.

PMID- 15730810
TI  - [Expression of NY-ESO-1/LAGE-1 genes in hepatocellular carcinoma and autologous
      humoral responses induced thereby].
AB  - OBJECTIVE: To investigate the potential of utilizing NY-ESO-1/LAGE-1 antigens in
      hepatocellular carcinoma (HCC) vaccines. METHODS: RT-PCR method was used to
      detect the expression of NY-ESO-1/LAGE-1 mRNA in the cancerous tissues and
      adjacent tissues resected from 34 patients with HCC. ELISA assay was adopted to
      analyze the NY-ESO-1 specific antibodies in 37 serum samples of HCC patients, 1
      positive control sample, and 8 samples of normal persons. RESULTS: Nine (26.5%)
      out of the 34 HCC samples were NY-ESO-1 mRNA positive, while 12 (35.3%) were LAGE
      1 positive. Among them, seven HCC samples expressed both genes, and 14 (41.6%)
      expressed at least one of the genes. Among the 37 serum samples tested six
      contained high titer of anti-NY-ESO-1 antibodies. Five of the samples were from
      stage III or later stage HCC patients; one was from a stage II patient.
      CONCLUSION: NY-ESO-1/LAGE-1 mRNA is expressed in a high frequency in HCC tissue
      samples, and induces autologous humoral responses in HCC patients. Both of the
      antigens can be considered as candidates for HCC vaccines.

PMID- 15730811
TI  - [Effects of donor-specific bone marrow cell infusion on chimerism and acute
      rejection in kidney transplantation].
AB  - OBJECTIVE: To evaluate the effect of donor-specific bone marrow cell infusion on
      the production of chimerism and acute rejection in kidney transplantation.
      METHODS: Sixty-one patients, 48 males and 13 females, aged 38.4 (23 - 45),
      underwent transplantation of cadaveric kidneys, 24 of which underwent kidney
      transplantation combined with donor-specific bone marrow cell infusion and 37 of
      which underwent pure transplantation of kidney. During the kidney transplantation
      combined with donor-specific bone marrow cell infusion the donor bone marrow
      cells (DBMC) were isolated from the thoracic vertebrae and iliac bones of the
      donors-cadavers and infused into the recipients of the kidneys of the same
      donors. After operation the peripheral blood was collected from the 61 recipients
      every 2 - 3 months for at least 1 year to undergo PCR to detect the presence of
      chimerism, and the rates of chimerism and acute rejection were compared between
      these 2 groups. RESULTS: During the follow-up the presence rate of chimerism was
      87.5% (21/24) in the marrow recipients, significantly higher than that in the
      control group (40.5%, 15/37, P < 0.001). The prevalence of acute rejection in the
      chimerism positive patients was 19.4% (7/16), significantly lower than that in
      the chimerism negative patients (44%, 11/25, P < 0.05). CONCLUSION: Donor
      specific bone marrow cell infusion in cadaver kidney transplantation induces the
      production of chimerism, and increases the immune tolerance to the donor organs,
      thus finally decreasing the incidence of acute rejection. Chimerism is correlated
      with immune tolerance.

PMID- 15730812
TI  - [Application of dynamic bubble trap in coronary artery bypass with
      cardiopulmonary bypass: an initial study].
AB  - OBJECTIVE: To investigate the effectiveness of dynamic bubble trap (DBT) on air
      microbubble elimination from both the cardiopulmonary bypass (CPB) circuit and
      middle cerebral arteries, and evaluate its possible impact on blood cells and
      coagulatory function. METHODS: Twenty patients undergoing coronary artery bypass
      graft (CABG), 12 males and 8 females, with similar perioperative data were
      assigned randomly to DBT group and control group. Each CABG was finished with
      identical circuit sets except the integration of a DBT between the arterial
      filtrator and the aortic cannula in the DBT group. Air microbubbles were detected
      before and after the integration of DBT with ultrasonographic detector and
      microembolism signals (MES) in middle cerebral arteries were counted by
      transcranial Doppler (TCD). Plasma free hemoglobin (PFH), lactate dehydrogenase
      (LDH), fibrinogen, platelet count, coagulation factor II and anti-thrombin III
      (ATIII) were also assayed respectively before the operation, at the termination
      of CPB, and 6 hours after the operation. RESULTS: In the DBT group the
      microbubbles of different size could be expelled significantly with the clearance
      rates between 68% - 74% (10 - 120 microm bubbles), 79% - 81% (20 - 120 microm
      bubbles), and 88% - 96% (40 - 120 microm bubbles). During the total CPB phase,
      the mean number of MES reached 197 +/- 137 in the control group and 158 +/- 178
      in the DBT group, without a significant difference between these 2 groups. The
      PFH and LDH levels raised while the platelet count, fibrinogen level, and
      coagulation factor II and AT III activities decreased sharply after CPB in these
      2 groups, however without significant differences in these parameters between the
      two groups. CONCLUSION: DBT integration into the CPB circuit enhances neither
      blood cell damage nor coagulation disturbance. DBT effectively eliminates air
      microbubbles in arterial conduit; however, its microembolus elimination function
      is prone to die down during the total period of CPB.

PMID- 15730813
TI  - [Chlamydia pneumoniae infection increases the risk of coronary artery disease in
      the patients with dyslipidemia].
AB  - OBJECTIVE: To investigates the role of chlamydia pneumoniae (CP) infection in the
      development of coronary artery disease (CAD) in the patients with dyslipidemia,
      and to examine the gender related differences in this role. METHODS: 523
      inpatients with dyslipidemia and 1196 inpatients without dyslipidemia tested for
      specific CP IgG by enzyme-linked immunoassay. Multivariate analyses were
      performed in the patients with and without dyslipidemia, and in the subgroups of
      male and female dyslipidemic patients to get the adjusted odds ratio (OR) (95%
      confidence intervals) of CAD for a given risk factor. RESULTS: After adjusting
      for age over 55 years, male sex, smoking, hypertension and diabetes, the OR of
      CAD associated with CP infection was 2.5 (1.4 to 4.6, P = 0.002) in the patients
      with dyslipidemia, and was 0.967 (0.7 - 1.4, P = 0.851) in those without
      dyslipidemia. In comparison with the male patients with dyslipidemia, the
      adjusted OR of CAD was 2.1 (1.1 to 4.1) for CP infection and 3.3 (1.9 - 5.9) for
      smoking; only CP infection was significantly contributed to CAD in female
      dylipidemic patients, with an adjusted OR of 4.4 (1.4 to 14.6). CONCLUSION: CP
      infection increases the risk of CAD only in patients with dyslipidemia, and this
      increase was greater in women than in men.

PMID- 15730815
TI  - [Xuan-xia-qu-du capsule combined with small dose of buprenorphine in the
      treatment of heroine dependence drug withdrawal syndrome ].

PMID- 15730816
TI  - [Influence of mechanical stress on chondrogenesis of in vitro cultured porcine
      bone marrow stem cells: a preliminary study].
AB  - OBJECTIVE: To evaluate the influence of mechanical stress on chondrogenesis of in
      vitro cultured porcine bone marrow stem cells (BMSC). METHODS: Porcine BMSC of
      passage 2 were seeded onto a cylinder-shaped PGA/PLA scaffold, 8mm in diameter
      and 3mm in thickness, at a density of 5 x 10(7)/cm(3). After the cell-scaffold
      constructs were cultured for one week, the primary medium, high-glucose DMEM
      medium with 10% fetal bovine serum (FBS), was replaced by chondrogenically
      inductive medium containing TGFbeta(1) (10 ng/ml), IGF-I (50 ng/ml), and
      dexamethasone (40 ng/ml) in addition to DMEM+10% FBS. The constructs were
      randomly divided into three groups according to the imposed stress: experimental
      group A in which a centrifugal stress was imposed at 100 g, 30 min, 2/d;
      experimental group B in which a rotative stress was imposed at 80 rpm, 8 h/d by a
      shaker; and control group in which the constructs were statically cultured. The
      gross view, histology, histochemistry, immunohistochemistry and glycosaminoglycan
      (GAG) content were evaluated after 4 and 8 weeks respectively. RESULTS: Four
      weeks later, the constructs in both experimental groups maintained their original
      sizes and shapes. Histology showed nodular lacuna-like structures, in company
      with GAG deposition and collagen synthesis. In addition, collagen type II was
      detected by immunohistochemistry. In the control group, however, the constructs
      shrunk to a little smaller size than those in the experimental groups, and
      histological staining showed a little amount of lacuna. Eight weeks later, the
      constructs in both experimental groups still maintained the original sizes and
      shapes with good elasticity. HE staining showed massive lacuna-like structures in
      most areas of the construct and extracellular matrix deposited evenly. Fibrous
      tissues were only observed in some areas. Safranin-O staining showed massive GAG
      formation and Masson staining showed much more collagen formation than those in
      the control group. Immunohistochemical staining of collagen type II showed strong
      positive expression. In the control group the constructs showed massive fibrous
      tissues, with a small amount of lacuna-like structures in the peripheral areas.
      GAG contents in the 2 experimental groups were 5.98 mg/g and 5.62 mg/g
      respectively, both significantly higher than that in the control group (4.73
      mg/g) without a difference between the 2 experimental groups. CONCLUSION:
      Mechanical stress promotes chondrogenesis and cartilage maturation of BMSC in
      vitro.

PMID- 15730818
TI  - [Mechanisms of purified cobra venom factor in preventing hyperacute rejection
      following discordant liver xenotransplantation in rats].
AB  - OBJECTIVE: To investigate the mechanisms of purified cobra venom factor (CVF) in
      preventing hyperacute rejection (HAR) and prolonging recipient survival following
      discordant liver xenotransplantation in rats. METHODS: All animals were divided
      into two groups, group I (n = 20), unmodified recipients as control; group II (n
      = 20), xenograft recipients were treated with 50 microg/kg CVF i.v. on day-1. The
      pathologic changes of liver were observed and TNF-alpha of blood serum was
      detected. RESULTS: Recipient survival after CVF treatment is significantly
      prolonged compared with unmodified recipients (1.8 +/- 0.6 vs.7.4 +/- 2.1 h, P <
      0.01). Histologically, widespread thrombosis, interstitial haemorrhage, C3
      deposits on sinusoids and central veins characterized xenografts of the control
      group. Xenografts of the CVF group showed endothelium swelling and cellular
      infiltrate, no deposit of C3 was detected. CONCLUSION: Purified CVF can prevent
      guinea pig-to-rat liver xenografts from HAR and extend recipient survival.
      Preconditioning with CVF, guinea pig-to-rat combination is a useful life
      supporting model to explore further mechanisms of discordant liver
      xenotransplantation.

PMID- 15730817
TI  - [Preliminary study of immunity and safety of recombinant adenovirus expressing
      rotavirus structural proteins in rhesus monkeys].
AB  - OBJECTIVE: To preliminarily evaluate the immunity and safety of the recombinant
      adenoviruses expressing rotavirus structural proteins VP7 and VP6 in rhesus
      monkeys to lay a foundation for the development of novel genetic engineering
      vaccine against rotavirus. METHODS: Baby monkeys were immunized with the
      recombinant adenoviruses intranasally or orally. Serum IgG against rotavirus was
      measured with ELISA. During the course of the immunization, besides the daily
      monitoring of body temperature, weight and clinical symptoms, the routine blood
      and urine tests and liver and kidney function tests were also conducted. RESULTS:
      Monkeys immunized via intranasal or oral routes could both generate serum IgG
      against rotavirus. During the immunization, the temperature of monkeys was normal
      and body weight raise stably. Both routine blood and urine tests and liver and
      kidney function tests showed no significant alteration compared with the control
      group. CONCLUSION: The immunization with the recombinant adenoviruses expressing
      rotavirus antigens is able to induce rotavirus specific efficient immune
      responses and is safe to baby rhesus monkeys. The preliminary results implied
      that the recombinant adenoviruses could be an ideal vaccine for rotavirus and lay
      a foundation for further studies.

PMID- 15730819
TI  - [Expression of aquaporin-4 water channel in the MRI graphic-ischaemic penumbra].

PMID- 15730820
TI  - [Changes of collagen expression of pulmonary arteries and heart ventricles and
      intervention of fosinopril and losartan in rats with heart failure].

PMID- 15730822
TI  - [Skin pigmentation, hypertension, hypokalemia, sex premature, extremity
      weakness,shortness--a case report ].

PMID- 15730821
TI  - [Development of a rat model for primary liver cancer with modified method].

PMID- 15730823
TI  - [Progress on the study of cerebral hemorrhage].

PMID- 15730824
TI  - [Guideline of clinical uses of antibiotics].

PMID- 15730825
TI  - Re-emphasizing the publication ethics.

PMID- 15730826
TI  - Characteristics and outcome of chest pain in young adults.
AB  - OBJECTIVE: To estimate the frequency of acute coronary syndrome (ACS) at 30 days
      in patients less than 40 years of age reporting with acute chest pain in
      Emergency Department (ED). DESIGN: Prospective cohort study. PLACE AND DURATION
      OF STUDY: Emergency Department (ED) of Aga Khan University Hospital, Karachi
      between July to December 2002. PATIENTS AND METHODS: One hundred young patients
      with chest pain in whom an electrocardiogram (ECG) was performed. A standardized
      data collection form was completed. Physical examination included initial vital
      signs and presence or absence of jugular venous pressure (JVP), rales, or fourth
      heart sound. Outcome variables were seen in the patients admitted or discharged
      within 30 days of reporting to the ED. RESULTS: Out of one hundred young patients
      in the study, 24 had an ACS. Of those, 22 (91.66%) were males and their mean age
      was 35 years. Most of these patients had cardiac risk factors on physical
      findings. The final diagnosis of patients consisted of 47 patients with atypical
      chest pain, 20 with acute myocardial infarction (AMI), 16 with musculoskeletal
      chest pain, 7 with psychogenic chest pain, 4 with angina, 4 with others and 2
      with gastritis. CONCLUSION: Young patients, presenting to ED with chest pain, had
      a greater likelihood of suffering from ACS if they were male and between 30 to 40
      years of age. People of any age group, presenting to ED with chest pain should
      not be disregarded in the presence of cardiac risk factors and positive physical
      findings.

PMID- 15730827
TI  - Ventricular tachycardia: a hospital perspective.
AB  - OBJECTIVE: To describe the etiology and outcome in patients with ventricular
      tachycardia in our patient population. DESIGN: A descriptive study. PLACE AND
      DURATION OF STUDY: The study was conducted at the Aga Khan University Hospital
      from November 2002 to October 2003. SUBJECTS AND METHODS: We enrolled 58 patients
      who presented to the emergency room with clinical and electrocardiographic
      evidence of ventricular tachycardia (VT) and/or who developed it during the
      inpatient stay at the Aga Khan University Hospital. Medical records were
      retrieved through the computerized data retrieval system. Patients above 18 years
      of age were included. Those with a pacemaker or who developed VT during
      electrophysiological testing were excluded. A pre-designed proforma was filled
      for all patients who fulfilled the inclusion criteria. All patients were worked
      up for etiological causes of ventricular tachycardia. Outcomes in the form of
      death or discharge were recorded. RESULTS: There were 58 patients who suffered
      ventricular tachycardias during the study period. These included 70.7 %( 42)
      males and 29.3 %( 16) females. Mean age of the patients was 57.06+/-11.84 years.
      Emergency room admissions accounted for 55.2% and ventricular tachycardia was
      seen in 44.8% during the inpatient stay. Unresponsiveness was the presenting
      symptom in 25.9%, chest pain in 24.1%, palpitations in 13.8% and ghabrahat in
      12.1% patients. Myocardial ischemia was seen in 43.5% of the patients while 23.2%
      had cardiomyopathy, followed by 33.3% miscellaneous. Out of the patients who had
      myocardial ischemia (43.5%), 76.6% had non-ST elevation myocardial infarction, 20
      % patients had ST elevation myocardial infarction and 3.3% had unstable angina.
      Hemodynamic instability was noted in 50%, who subsequently required
      defibrillation. The mortality among these patients with VT was 13.7%. CONCLUSION:
      Myocardial ischemia was most commonly seen in patients with ventricular
      tachycardia in our group of patients. Ventricular tachycardia is associated with
      a significant mortality of 13.7%.

PMID- 15730828
TI  - Fine needle aspiration cytology versus histopathology in the diagnosis of
      cutaneous leishmaniasis in Pakistan.
AB  - OBJECTIVE: To compare FNAC with histopathology as an alternate method of
      diagnosing cutaneous leishmaniasis. DESIGN: Comparative study. PLACE AND DURATION
      OF STUDY: The duration of the study was from August 2003 to April 2004 at CMH,
      Peshawar. MATERIALS AND METHODS: A total of 40 patients were included in this
      study. They were referred from various areas of North-West Frontier Province.
      FNAC and skin biopsy was performed on every patient. Haematoxylin and eosin (H&E)
      stain was used for both procedures. RESULTS: The study group included 39 males
      and one female, their age ranging from 8-60 years with a mean age of 31.97 years.
      Detection of LT bodies was considered as a single criterion of the positive
      result. Histopathological examination was able to diagnose 14 out of 40 patients
      (positive yield of 35%), while FNAC picked up 11 out of 40 patients (positive
      yield of 27.5%). CONCLUSION: FNAC is easier, less painful and more cost-effective
      than the conventional skin biopsy. The high sensitivity and specificity eliminate
      the need for other time-consuming and invasive procedures. However, if LT bodies
      are not detected then any further comment cannot be made regarding the diagnosis
      and it is necessary to perform skin biopsy.

PMID- 15730829
TI  - Comparison of risk factors for diabetes in children of different socioeconomic
      status.
AB  - OBJECTIVE: To compare the risk factors for diabetes in children of two different
      socioeconomic status. DESIGN: A cross-sectional analytical study. PLACE AND
      DURATION OF STUDY: Visits to one government (low income) and two private (middle
      income) schools of Karachi in 1999 and 2000. PATIENTS AND METHODS: A total of 260
      children; 157 children (mean age 12.10 +/- 4 years) from low-income group and 103
      children (mean age 10.6 +/- 0.9 years) from middle-income group were surveyed.
      Data of physical fitness score (PFS) and BMI was calculated. Dietary records were
      taken by 24 hours self-reported diet recall charts of two weekdays. Knowledge
      about health was obtained by a questionnaire given to children and mothers.
      RESULTS: A significant difference was found in the mean age of low-income and
      middle-income groups (p-value < 0.001). Significant association was seen in low
      income group compared to middle-income group on the basis of TV viewing (p-value
      = 0.04). BMI (p-value = 0.011) and positive family history of diabetes (p-value <
      0.001). Forty-seven percent (n=74) of children from low-income group while 51%
      (n=53) of middle-income group had poor knowledge about health. The children in
      both the groups also consumed inadequate amount of calories, the diet being poor
      in fruit, vegetables and milk and high in the fat content. CONCLUSION: Although
      children in both the groups had increased risk factors for diabetes the
      difference between the two socioeconomic groups was significant in terms of
      middle-income children having more risk. Thus, changes in lifestyle and behaviour
      including diet is needed in this high risk group to prevent future generations
      from developing diabetes.

PMID- 15730831
TI  - Transcatheter embolization of acute non-variceal gastrointestinal hemorrhage.
AB  - OBJECTIVE: To determine the efficacy and safety of transcatheter embolization of
      nonvariceal gastrointestinal hemorrhage. DESIGN: Descriptive analytical study.
      PLACE AND DURATION OF STUDY: Radiology Department, The Aga Khan University
      Hospital, Karachi, Pakistan, from October 1999 to August 2004. SUBJECTS AND
      METHODS: The study included 27 patients who underwent angiography for suspected
      gastrointestinal hemorrhage. The presumptive diagnosis was based on the findings
      of endoscopy in 08 patients, scintigraphy in 05 patients and on clinical findings
      only in 14 patients. Nine patients had gastroduodenal hemorrhage, 04 patients had
      hemobilia and 14 patients had lower gastrointestinal bleeding. Five patients had
      comorbidities. One patient had uremia, 2 had hepatitis C, 1 had cirrhosis and 1
      had coagulopathy. Technical success, clinical success, complications and patient
      survival were assessed. RESULTS: Nine patients had upper gastrointestinal
      hemorrhage, 4 patients had hemobilia and 14 patients had lower gastrointestinal
      bleeding. Etiology of bleeding was known in 15 patients and unknown in 12
      patients. Clinical success was achieved in 23 (85.18%) of 27 patients. Two
      patients had early rebleeding. One of these was managed surgically and recovered.
      The other had severe coagulopathy and was unfit for surgery. Two patients had
      bowel infarction, one of these was managed surgically and recovered and the other
      died of complication of procedure. One patient had small splenic infarcts and was
      managed conservatively. Overall 85.18% success was achieved for the embolization
      procedure. Two of 27 patients died. One patient died because of recurrence of
      bleeding and other died because of infarction of right hemi-colon which occurred
      as complication of embolization. CONCLUSION: Transcatheter embolization is
      effective and safe in patients with nonvariceal gastrointestinal hemorrhage.

PMID- 15730832
TI  - The role of amniotic fluid index in the management of postdate pregnancy.
AB  - OBJECTIVE: To evaluate the role of amniotic fluid index as a reliable fetal
      surveillance test in the management of postdate pregnancy. DESIGN: Cross
      sectional analytical study. PLACE AND DURATION OF STUDY: Hamdard University
      Hospital from May 2000 till May 2003. MATERIALS AND METHODS: A total of 210
      patients were studied. The antenatal fetal surveillance in these patients was
      based on ultrasound assessment of AFI twice weekly after 41 weeks. An abnormal
      AFI was defined as 6 cm , between 6 - 8 cm as equivocal and more than or equal to
      8 as normal. Delivery outcome and early neonatal complications were main
      outcomes. RESULTS: Rate of caesarean section (35.8%) in the women with AFI 6 cm
      was found significantly higher than 8.9% rate of caesarean section of the women
      having AFI > 6 cm (p = 0.001). Proportion of early neonatal complications was
      also significantly higher in the women with AFI 6 cm (p = 0.03). Out of a total
      210 fetuses, 38 (18.1%) neonates were found with early complications, of these,
      24 (63.2%) neonates were those whose AFI was 6 cm. Sensitivity of AFI was 63.2%
      while specificity was 83.1% as the power of reliable fetal surveillance.
      CONCLUSION: AFI is a reliable fetal surveillance test. It may allow the
      conservative approach till 42 weeks to reduce the caesarean section rate due to
      failed induction of labour as well as perinatal morbidity and mortality.

PMID- 15730830
TI  - Treatment of chronic hepatitis B with lamivudine.
AB  - OBJECTIVE: To study the efficacy of antiviral drug lamivudine for treatment of
      chronic hepatitis B in Pakistani population. DESIGN: Experimental study. PLACE
      AND DURATION OF STUDY: A tertiary Care Center, from January 2000 to January 2004.
      PATIENTS AND METHODS: Patients who had positive hepatitis B surface antigen
      (HBsAg) and elevated ALT were recruited. Both hepatitis Be antigen (HBeAg)
      positive and HBeAg negative patients were included. Treatment was given with
      lamivudine 100mg once a day for 12 months and they were followed every 2-3 months
      with ALT, HBeAg, and in certain cases with, HBV DNA (PCR). Those patients who
      were HBeAg positive were considered to have achieved end of treatment response
      (ETR) when ALT was normal and HBeAg was negative and this was documented at two
      consecutive occasions, at least one month apart. Those patients who were HBeAg
      negative were considered to have achieved ETR when their ALT was normal and HBV
      DNA was undetectable. Patients were followed for further 6 months to evaluate for
      any relapse. RESULTS: A total of 105 patients were included. Eighty-two (78.1%)
      were males and 23 (21.9%) were females. Mean ALT of all patients was 87.15 +/-
      46.01 u/dl. Seventy-two HBeAg positive and 15 HBeAg negative patients completed
      treatment with 23.6 % and 80.0 % response rate respectively (p <0.001).
      CONCLUSION: The response of lamivudine in chronic hepatitis B in Pakistani
      population is encouraging in HBeAg negative patients but is rather low in those
      who are HBeAg positive.

PMID- 15730833
TI  - Temporal fascia as interpositioning material in cases of temporomandibular
      ankylosis.
AB  - OBJECTIVE: To evaluate the efficacy of temporal fascia as interpositioning
      material after treatment of TMJ ankylosis with gap arthroplasty. DESIGN: An
      interventional study. PLACE AND DURATION OF STUDY: The study was carried out at
      the Department of Oral and Maxillofacial Surgery, Mayo Hospital, Lahore, during
      June 1999 to June 2001. PATIENTS AND METHODS: A total of 51 patients, 23 males
      and 28 females, of temporomandibular ankylosis were treated with gap arthroplasty
      and temporal fascia was used as interpositioning material. RESULTS: Out of 51
      cases, 28 had excellent results, 20 were declared good and 3 presented with
      recurrence. CONCLUSION: Temporal fascia works as excellent interpositioning
      material with minimum morbidity and no complications. Moreover, it is easier to
      raise, comes from same operation field and is dispensable.

PMID- 15730834
TI  - Risk factors associated with development of ventilator associated pneumonia.
AB  - OBJECTIVE: To assess the risk factors associated with development of ventilator
      associated pneumonia (VAP). DESIGN: A case control study. PLACE AND DURATION OF
      STUDY: Intensive Care Unit (ICU) at the Aga Khan University Hospital, Karachi,
      between January 1999 and June 2000. PATIENTS AND METHODS: All patients with
      assisted mechanical ventilation were assessed for the development of VAP. Risk
      factors associated with development of VAP were determined. Adult patients who
      developed pneumonia, 48 hours after ventilation, were called cases while those
      who did not develop pneumonia were called controls. RESULTS: Seventy (28%) out of
      250 mechanically ventilated patients developed VAP (rate of VAP was 26 cases per
      1000 ventilator days). Shock during first 48 hours of ventilation (odds ratio
      (OR), 5.95; 95% confidence interval (CI), 2.83-12.52), transport out of ICU
      during mechanical ventilation (OR, 6.0; 95% CI, 2.92-12.37), re-intubation (OR,
      4.23; 95% CI, 2.53-9.85), prior episode of aspiration of gastric content (OR,
      3.07; 95% CI, 1.35-7.01), and use of antibiotics prior to intubation (OR,2.55;
      95% CI, 1.20-5.41) were found to be independently associated with a higher risk
      of developing VAP. Gram negative organisms and Staphylococcus aureus were
      responsible for over 90% of cases. Patients with VAP had higher crude mortality
      rate (57.1%) compared with controls (32.2%). CONCLUSION: Ventilator associated
      pneumonia is associated with a high mortality. This study has identified risk
      factors associated with VAP.

PMID- 15730835
TI  - Risk factors in high altitude pulmonary oedema.
AB  - OBJECTIVE: To identify the risk factors for high altitude pulmonary oedema.
      DESIGN: A case control study. PLACE AND DURATION OF STUDY: The study was
      conducted in the Department of Medicine, Military Hospital, Rawalpindi during
      October 1998 to October 2000. SUBJECTS AND METHODS: One hundred serving army
      personnel between 20 to 50 years of age were divided in two groups. First group
      comprised of 50 patients who developed high altitude pulmonary oedema at 4000
      meters height and above. Second group consisted of 50 control subjects who
      accompanied the patients. Detailed history was obtained regarding height of
      native dwelling, rate of ascent, amount of exertion and preceding respiratory
      tract infection. The findings of both the groups were compared and statistically
      analyzed by application of Pearson's chi-square test. Difference was considered
      significant when p-value was < 0.05. RESULTS: All the subjects were male. Average
      age of the indexed group was 29.4(+/- 4) years as compared to 27(+/- 5) years in
      the control group. Six patients (12%) were highland dwellers whereas 44 patients
      (88%) were inhabitants of lower heights. Average rate of ascent from 4000 meters
      to 4500 meters of the indexed group was 5(+/- 2) days while in control group it
      was 10(+/- 3) days. Twenty cases (40%) had history of severe exertion whereas
      such history was not present in any of the control group subjects. Only 2
      patients had signs and symptoms of preceding respiratory tract infection.
      CONCLUSION: Rapid rate of ascent, extreme physical exertion, low height of native
      dwelling and preceding respiratory tract infection are important risk factors for
      the development of high altitude pulmonary oedema. Proper acclimatization with
      gradual ascent plays important role in preventing this potentially fatal
      condition.

PMID- 15730837
TI  - Monitoring of HBe antigen and alanine aminotransferase levels in hepatitis B
      virus DNA positive patients.

PMID- 15730836
TI  - Organophosphorus insecticide poisoning: management in surgical intensive care
      unit.
AB  - OBJECTIVE: To evaluate the outcome of patients with organophosphorus poisoning.
      DESIGN: Descriptive (non-interventional) study. PLACE AND DURATION OF STUDY:
      Surgical Intensive Care Unit, Civil Hospital Karachi, from January 1996 to
      December 2002. PATIENTS AND METHODS: Medical records of all the patients with
      organophosphorus poisoning, admitted during the study period, were reviewed.
      Their clinical features, complications, management and survival were noted.
      RESULTS: Out of 52 patients, admitted to surgical intensive care unit during the
      study period, 92.31% survived and were discharged to medical wards. Major cause
      of mortality (7.69 %) was acute respiratory distress syndrome. CONCLUSION: The
      common cause of mortality in organophosphorus poisoning is aspiration pneumonia
      leading to acute respiratory distress syndrome that is preventable by securing
      the airway early in emergency room.

PMID- 15730838
TI  - Role of primary healthcare and innovative strategies in improving knowledge and
      practice of mothers regarding diarrhoeal diseases in a squatter settlement of
      Karachi.

PMID- 15730839
TI  - Familial homocystinuria.
AB  - Two cases of siblings diagnosed as cases of familial homocystinuria are reported.
      Both the cases have classical presentation of familial homocystinuria including
      history of dislocation of lens of the right eye. Brother had history of
      psychomotor retardation while sister had a significant history of deep vein
      thrombosis. Levels of plasma homocysteine were elevated and urinary homocysteine
      was positive in both the cases.

PMID- 15730840
TI  - Spontaneous multivessel coronary artery dissection associated with elevated
      homocysteine levels.
AB  - A case of spontaneous multi-vessel coronary artery dissection in a young man,
      with markedly elevated serum homocysteine levels, is reported. The effects of
      elevated homocysteine levels on arterial endothelial function and possible plaque
      rupture leading to coronary dissection and acute coronary syndrome and / or
      sudden cardiac death are also discussed.

PMID- 15730841
TI  - Acquired hepatocerebral degeneration in hepatitis C infection.
AB  - Patients with chronic liver disease (CLD) often have neurological sequelae, of
      which hepatic encephalopathy is the most frequent and reversible. Rare
      irreversible complications of CLD are acquired (non Wilsonian) hepatocerebral
      degeneration (AHCD) and hepatic myelopathy (HM). To our knowledge, AHCD has
      rarely been reported in patients with hepatitis C virus (HCV) infection. We
      report a patient with HCV infection who developed AHCD and resulted in serious
      complications.

PMID- 15730842
TI  - Cervical vagus nerve schwannoma.
AB  - Schwannomas arising from cervical cranial nerves rarely present as neck swelling.
      Ultrasonography, computerised tomography, magnetic resonance imaging and fine
      needle aspiration cytology are helpful in reaching a diagnosis. Surgical excision
      is the treatment of choice. A case of large cervical vagus nerve schwannoma
      occurring in a young lady is presented with its management.

PMID- 15730843
TI  - Ganglioneuroma of the cervical spine.
AB  - This case report describes a young lady who presented with complaints of neck
      pain and weakness of all four limbs for the last eight months. Magnetic Resonance
      Imaging (MRI) scan of cervical spine revealed dumbbell shaped extramedullary
      lesion at C-3 and C-4 level extending outside through neural foramen of C-3. She
      underwent extended cervical laminectomy from C-3 to C-7 level. Postoperatively
      power was gradually regained in all four limbs. Histopathology confirmed a case
      of ganglioneuroma.

PMID- 15730844
TI  - Posttransplant Guillain Barre Syndrome.
AB  - This case report describes a patient with severe aplastic anaemia, who developed
      Guillain Barre Syndrome (GBS) 10 weeks after allogeneic haematopoietic stem cell
      transplantation (HSCT) from HLA-matched sibling-younger sister. GBS was preceded
      by pneumonia, herpes labialis and oral candidiasis a week earlier. Treatment with
      ventilatory management, intravenous human immunoglobulin (IVIg) and
      antimicrobials resulted in smooth recovery in thirty-one days.

PMID- 15730845
TI  - Persistent mullerian duct syndrome with transverse testicular ectopia.
AB  - A case report of a 3 months old male child is presented, who had right inguinal
      hernia with left impalpable testis. During herniotomy we found both testes on
      right side (transverse testicular ectopia) with presence of mullerian duct
      structures.

PMID- 15730846
TI  - Post-colectomy peristomal pyoderma gangrenosum.
AB  - We report a patient with peristomal pyoderma gangrenosum which mimicked a
      necrotizing bacterial infection. It occurred as an extra-intestinal manifestation
      of chronic mucosal ulcerative colitis (MUC). Initially misdiagnosed as a
      cutaneous infection, it finally responded to intravenous high dose corticosteroid
      therapy.

PMID- 15730847
TI  - Squamous cell carcinoma lower lip - an experience with Karapandzic technique.
AB  - Carcinoma of the lip is a common cancer of head and neck area. It occurs
      frequently on the lower lip of middle-aged and elderly males who have a history
      of chronic sun exposure. Surgical excision and radiotherapy are regarded as
      equally effective treatment options, but preferred method is surgical excision.
      Karapandzic technique provides myoneurovascular pedicled advancement flap for
      reconstruction of the defect after surgical excision. It is a simple and safe
      technique, functionally and esthetically, sacrifices little tissue, heals rapidly
      and is effective for repair of defects covering 1/3 to 4/5 of the lower lip. We
      report a 62 years male who presented with a large, fungating, pus-discharging and
      tender mass of lower lip. Biopsy confirmed squamous cell carcinoma. Tumor was
      excised and defect was reconstructed using Karapandzic technique. Patient
      remained asymptomatic during follow-up visits.

PMID- 15730848
TI  - Meta-analysis of new treatment strategies for metastatic colorectal cancer.

PMID- 15730850
TI  - MIP-1alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and
      increase adhesion of myeloma cells to marrow stromal cells.
AB  - OBJECTIVES: Macrophage inflammatory protein-1alpha (MIP-1alpha), an osteoclast
      (OCL) stimulatory factor produced by primary multiple myeloma (MM) cells,
      increases bone destruction and tumor burden in murine models of MM. Several
      chemokine receptors (CCR1, CCR5, and CCR9) mediate the effects of MIP-1alpha. In
      this study, we determined which of these mediates the effects of MIP-1alpha on
      human OCL formation and myeloma cells. METHODS: We employed RT-PCR analysis,
      neutralizing antibodies to CCR1 and CCR5 as well as a CCR1-specific antagonist
      and OCL formation assays to identify the MIP-1alpha receptors involved in MIP
      1alpha's effects on myeloma cells and OCL formation. RESULTS: RT-PCR analysis
      demonstrated that both CCR1 and CCR5 were expressed by highly purified human OCL
      precursors, myeloma cell lines, and purified marrow plasma cells from MM
      patients. Neutralizing antibodies to CCR1 or CCR5 inhibited MIP-1alpha-induced
      OCL formation. Furthermore, monocyte chemotactic protein-3 (MCP-3), which binds
      CCR1 but not CCR5 and the CCR1-specific antagonist, BX471, markedly inhibited OCL
      formation stimulated with MIP-1alpha. Anti-CCR1, anti-CCR5, or BX471 also
      inhibited the upregulation of beta1 integrin mRNA in myeloma cells induced by MIP
      1alpha, as well as the adherence of myeloma cells to stromal cells and IL-6
      production by stromal cells in response to myeloma cells. CONCLUSION: These data
      demonstrate that MIP-1alpha utilizes either CCR1 or CCR5 for its effects on OCL
      formation and myeloma cells, and that blocking either CCR1 or CCR5 inhibits OCL
      formation and myeloma cell adhesion to stromal cells.

PMID- 15730849
TI  - Control of globin gene expression during development and erythroid
      differentiation.
AB  - Extensive studies during the last 30 years have led to considerable understanding
      of cellular and molecular control of hemoglobin switching. Cell biology studies
      in the 1970s defined the control of globin genes during erythroid differentiation
      and led to development of therapies for sickle cell disease. Molecular
      investigations of the last 20 years have delineated the two basic mechanisms that
      control globin gene activity during development--autonomous silencing and gene
      competition. Studies of hemoglobin switching have provided major insights on the
      control of gene loci by remote regulatory elements. Research in this field has an
      impact on understanding regulatory mechanisms in general and is of particular
      importance for eventual development of molecular cures for sickle cell disease
      and beta thalassemia.

PMID- 15730851
TI  - CD34, CD4, and CD8 cell doses do not influence engraftment, graft-versus-host
      disease, or survival following myeloablative human leukocyte antigen-identical
      peripheral blood allografting for hematologic malignancies.
AB  - OBJECTIVES: Optimal granulocyte colony-stimulating factor-mobilized peripheral
      blood progenitor cell (G-PBMC) graft compositions for myeloablative allogeneic
      hematopoietic cell transplantation (AHCT) have not been identified. G-PBMC cell
      contents were analyzed for influence on outcomes. PATIENTS AND METHODS: Human
      leukocyte antigen(HLA)-identical related donor AHCT was used to treat 101
      patients with hematologic malignancies at a single institution between 1995 and
      2002. CD34+, CD3+, CD4+, and CD8+ cell doses were enumerated by flow cytometry
      and evaluated by univariate analysis. RESULTS: Categorized by the median of cell
      doses infused, no G-PBMC cell dose significantly correlated with neutrophil and
      platelet engraftment. Incidence of grade II to IV acute graft-versus-host disease
      (GVHD) was 24.6% (95% confidence interval [CI]: 15.9-33.3) and was not
      significantly influenced by evaluated G-PBMC cell doses. With a median follow-up
      time of 18 months for surviving patients, estimates for extensive chronic GVHD
      was 43.8% (95% CI: 31.4-56.2), for freedom from progression was 69.5% (95% CI:
      58.1-80.9), and for overall survival was 46.9% (95% CI: 35.5-58.3). CD34+, CD3+,
      CD4+, and CD8+ cell doses were not significantly predictive of extensive chronic
      GVHD, freedom from progression or overall survival. Additionally, comparing
      patients receiving the upper versus lower 33rd percentiles of CD34+ cell dose,
      associations with extensive chronic GVHD remained insignificant (p=0.21; relative
      risk (RR)=1.7; 95% CI: 0.7-3.9). CONCLUSIONS: G-PBMC graft content does not
      influence outcomes after myeloablative AHCT. In particular, no significant
      association between extensive chronic GVHD was identified with any G-PBMC cell
      dose, including CD34.

PMID- 15730852
TI  - Failure to define window of time for autologous tumor vaccination in patients
      with newly diagnosed or relapsed acute lymphoblastic leukemia.
AB  - OBJECTIVES: We and others have shown that B cell precursor acute lymphoblastic
      leukemia cells (ALL) stimulated with CD40 ligand become efficient antigen
      presenting cells (APC) capable of expanding autologous, tumor-specific T cells
      from patients. Translation of these preclinical findings to a novel treatment
      strategy required four separate issues to be determined: (1) if a CD40-ALL
      vaccine could be generated for clinical use; (2) whether clinical translation
      could be achieved; (3) whether the vaccination was safe; and (4) whether a window
      of time could be identified that would optimize the efficacy of vaccination.
      PATIENTS AND METHODS: Nine patients with relapsed/refractory ALL were enrolled in
      a phase I trial of vaccination with autologous CD40-ALL. Immunologic
      reconstitution was measured in a separate cohort of 23 patients with newly
      diagnosed ALL. RESULTS: We successfully prepared autologous vaccines for all nine
      patients in the phase I trial. CD40-ALL were potent APC, capable of stimulating
      allogeneic and peptide-specific T cells in vitro. Two patients were vaccinated
      without adverse events. Five patients died or progressed before vaccination,
      suggesting that rapid disease progression limits vaccination in patients with
      relapse disease, thus limiting clinical translation. We therefore sought to
      identify a window of time for vaccination during which this approach might be
      feasible. To achieve this end, we evaluated immunological reconstitution in newly
      diagnosed patients with ALL patients. Despite recovery of myelopoiesis, most
      patients had profound defects in T, B, and natural killer (NK) cell numbers that
      failed to recover at any point during therapy. CONCLUSION: Autologous tumor
      vaccination at a time of ALL relapse is not feasible. Alternative strategies for
      immunotherapy of ALL may require ex vivo generation of antigen specific T cells
      and adoptive therapy.

PMID- 15730853
TI  - The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear
      neutrophils and hematopoietic progenitor cells into peripheral blood and
      synergizes with granulocyte colony-stimulating factor.
AB  - OBJECTIVE: Mobilization of hematopoietic stem and progenitor cells (HSPC) by
      stromal cell-derived factor-1 (SDF-1) has been described; however, sustained
      adenoviral delivery or N-terminal modification was required for effect and could
      not be demonstrated with native protein. The aim of this study was to further
      investigate the SDF-1alpha/CXCR4 axis in HSPC mobilization using CTCE-0021, a
      cyclized CXCR4 agonist peptide, with comparable bioactivity and improved
      stability relative to SDF-1alpha. METHODS: Peripheral blood cells and
      hematopoietic progenitor cells (HPC) were quantitated in mice administered single
      or multiple doses of CTCE-0021 or SDF-1alpha, or mobilized by granulocyte colony
      stimulating factor (G-CSF) in combination with CTCE-0021. Proteases, cytokines,
      and receptors implicated in HSPC mobilization were evaluated to determine
      mechanism of action. RESULTS: CTCE-0021 dose-dependently elevated blood
      neutrophils polymorphonuclear neutrophil [PMN] within 5 minutes that peaked after
      1 hour and persisted for 24 hours. PMN mobilization could be maintained by daily
      dosing. CTCE-0021 mobilized colony-forming unit granulocyte macrophage (CFU-GM),
      burst-forming unit erythroid (BFU-E), and CFU-granulocyte-erythrocyte-monocyte
      megakaryocyte (CFU-GEMM) that peaked within 1 hour after administration, and
      synergistically enhanced both PMN and HSPC mobilization when combined with G-CSF.
      Mobilization induced by CTCE-0021 was associated with rapid downregulation of
      CXCR4 expression on HPC. No appreciable changes in proteases implicated in HPC
      mobilization were observed. Significantly elevated plasma SDF-1 was detected in
      mobilized mice, which likely represents CTCE-0021. CONCLUSION: These studies
      indicate that CTCE-0021 is an efficient and rapid mobilizer of PMN and HPC when
      used alone and shows synergistic activity when used in combination with G-CSF.
      The mobilizing effect of this peptide appears to be mediated by downregulation of
      the CXCR4 receptor on HPC and altered chemokine gradient.

PMID- 15730855
TI  - In vitro functional defects of bone marrow-derived CD34+ progenitors from newly
      diagnosed mature B-cell malignancies with bone marrow tumor involvement.
AB  - OBJECTIVE: We hypothesized that the presence of tumor cells in bone marrow (BM)
      could alter hematopoietic progenitor cell functions. Therefore, we evaluated
      phenotypic and in vitro functional properties of BM-derived CD34+ progenitors
      issued from untreated and newly diagnosed patients presenting a mature B
      lymphoproliferative disorder (LPD) involving the BM (Inv+). PATIENTS AND METHODS:
      In vitro proliferation and differentiation capacities of primitive and committed
      progenitors were evaluated by cobblestone area-forming cell (CAFC) and colony
      forming cell (CFC) assays, and ex vivo cell expansion. Migratory capacities of
      CD34+ cells were explored by chemotaxis assays using a CXCL12alpha gradient.
      RESULTS: Our results showed that CD34+ cells from Inv+ patients overexpressed
      CD117 and had a significant decrease of week-3 and -6 CAFC, and CFC frequencies,
      compared to cells obtained from healthy volunteers and LPD patients without BM
      involvement (Inv-). In addition, progenitors from Inv+ patients maintained a
      significantly decreased CFC capacity after ex vivo cell expansion, compared to
      healthy volunteers. However, the former cells held their migratory capacity in
      response to CXCL12alpha. CONCLUSION: Functional defects of primitive and
      committed CD34+ progenitors detected among LPD patients with BM tumor involvement
      suggest either that tumor cells may induced bystander effects on progenitors or
      that "unusual" CD34+ cells may exist in the BM that could belong to the
      proliferating tumor tissue.

PMID- 15730856
TI  - Synergistic action of resveratrol, an ingredient of wine, with Ara-C and
      tiazofurin in HL-60 human promyelocytic leukemia cells.
AB  - OBJECTIVE: Resveratrol, a naturally occurring stilbene derivative, is a potent
      free-radical scavenger causing a number of biochemical and antineoplastic
      effects. It was shown to induce differentiation and apoptosis in leukemia cells.
      Resveratrol was also identified as an inhibitor of ribonucleotide reductase (RR),
      a key enzyme of DNA synthesis. We report about the biochemical effects of
      resveratrol on the concentration of deoxyribonucleoside triphosphates (dNTPs),
      the products of RR, and on the incorporation of 14C-labeled cytidine into the DNA
      of HL-60 human promyelocytic leukemia cells. MATERIALS AND METHODS: Incorporation
      of 14C-labeled cytidine into the DNA of resveratrol-treated HL-60 cells was
      measured. Concentration of dNTPs was determined by a HPLC method. Cytotoxic
      effects of resveratrol, Ara-C, and tiazofurin were analyzed using growth
      inhibition and clonogenic assays. Induction of apoptosis was studied using a
      Hoechst/propidium iodide staining method. RESULTS: We found that resveratrol
      effectively inhibited incorporation of 14C-labeled cytidine into DNA.
      Furthermore, incubation of HL-60 cells with resveratrol significantly decreased
      intracellular dCTP, dTTP, dATP, and dGTP concentrations. Based on these results,
      we investigated the combination effects of resveratrol with Ara-C or tiazofurin,
      both antimetabolites, which are known to exhibit synergistic effects in
      combination with other inhibitors of RR. In growth inhibition, apoptosis, and
      clonogenic assays, resveratrol acted synergistically with both Ara-C and
      tiazofurin in HL-60 cells. CONCLUSIONS: We conclude that resveratrol could become
      a viable candidate as one compound in the combination chemotherapy of leukemia
      and therefore deserves further testing.

PMID- 15730854
TI  - Cytokine signals through STAT3 promote expression of granulocyte secondary
      granule proteins in 32D cells.
AB  - OBJECTIVE: In a previous study, we showed that activation of a transfected human
      erythropoietin receptor (EPOR) in the murine myeloid cell line 32D resulted in
      the development of morphologic features of granulocytic differentiation and
      expression of the neutrophil primary granule protein myeloperoxidase. We now
      studied if EPOR signaling could also mediate secondary granule protein gene
      expression and investigated the signal transduction requirements for induction of
      secondary granule gene expression in 32D cells. MATERIALS AND METHODS: Wild-type
      and variant 32D cells expressing normal or chimeric EPORs or receptors for
      granulocyte colony-stimulating factor (G-CSFRs) were stimulated with EPO or G-CSF
      and the expression of granulocyte-specific genes was analyzed by Northern blot
      analysis. To determine the signaling mechanisms required for secondary granule
      protein gene induction, the activation of STAT pathways following growth factor
      stimulation was studied by Western blot analysis. RESULTS: We found that EPO
      treatment of 32D cells engineered to express EPOR did not result in induction of
      the secondary granule protein genes encoding lactoferrin and 24p3 lipocalin, the
      mouse homolog of human N-Gal, or the myeloid transcription factor C/EBPepsilon.
      Replacement of the intracellular domain of EPOR with the intracellular domain of
      G-CSFR in a chimeric receptor was associated with EPO-mediated induction of
      lactoferrin, 24p3 lipocalin, and C/EBPepsilon genes. We found that STAT3
      phosphorylation was mediated by the intracellular domain of G-CSFR, but not EPOR.
      Replacement of one or two of the STAT5 binding sites in the intracytoplasmic
      domain of the EPOR with STAT3 binding sites resulted in EPO-mediated STAT3
      activation and a marked increase in the expression of the 24p3 lipocalin gene.
      Knockdown of STAT3 protein levels with siRNA caused significant decrease in 24p3
      lipocalin gene induction. CONCLUSION: These results indicate that EPOR signaling
      cannot substitute for G-CSFR signaling to stimulate secondary granule protein
      gene expression in 32D cells. In addition, STAT3 is a critical mediator of 24p3
      lipocalin gene expression in these cells.

PMID- 15730857
TI  - Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in
      vivo.
AB  - OBJECTIVE: OX40, a member of the TNF receptor superfamily, and its ligand (OX40L)
      play crucial roles in induction and maintenance of integrated T cell immune
      response. Engagement of OX40L delivers a costimulatory signal to T cells. In this
      study, we investigated whether inoculation of OX40L-transfected EL4, a murine T
      cell lymphoma cell line, could induce anti-lymphoma immunity in mice. MATERIALS
      AND METHODS: Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental
      EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4
      (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen
      cells, and the immunohistochemistry were compared. RESULTS: While both parental
      EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than
      parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8
      mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T
      cells were involved in anti-lymphoma immunity. The immunohistochemical study
      revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro
      CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had
      significant cytotoxic activity against parental EL4. CONCLUSION: The gene
      transfer of OX40L into lymphoma cells is an eligible and efficient modality to
      induce anti-lymphoma immunity.

PMID- 15730858
TI  - Mechanisms of resistance to natural killer cell-mediated cytotoxicity in acute
      lymphoblastic leukemia.
AB  - OBJECTIVE: Natural killer (NK) cell-mediated cytotoxicity contributes to the
      innate immune response against numerous malignancies, including leukemias. Acute
      lymphoblastic leukemias (ALL) often display a high degree of resistance, the
      mechanisms of which have not been elucidated. METHODS: We used the well
      characterized NK cell line NK-92 as a model to investigate whether mechanisms
      commonly implicated in tumor escape from NK cell killing are relevant for ALL.
      RESULTS: We demonstrate selective resistance of B-precursor ALL to NK-92
      cytotoxicity even in the absence of inhibitory killer cell immunoglobulin-like
      receptors (KIR), except for KIR2DL4. We also show that human leukocyte antigen-G,
      a ligand of KIR2DL4, expressed on a subset of ALL, does not mediate resistance of
      NK-cell mediated lysis. Similarly, intracellular adhesion molecule/lymphocyte
      function-associated antigen-1 interaction did not contribute significantly to
      resistance. In contrast the NK-sensitive T-ALL (MOLT-4) expressed moderate
      amounts of MHC class I chain-related gene AB (MICA/B) a ligand for the NK cell
      activating receptor NKG2D, while expression of MICA/B was absent in resistant B
      ALL cell lines. CONCLUSIONS: The NK cell-resistance of B-lineage ALLs does not
      appear to involve inhibitory mechanisms, but suggests deficient NK cell
      activation. Thus, immunostrategies designed to enhance ALL sensitivity toward NK
      cell-mediated cytotoxicity should focus on mechanisms of NK cell activation.

PMID- 15730859
TI  - Increased longevity of hematopoiesis in continuous bone marrow cultures and
      adipocytogenesis in marrow stromal cells derived from Smad3(-/-) mice.
AB  - OBJECTIVE: To determine the role of Smad3 in modulating hematopoiesis, continuous
      bone marrow cultures were established from Smad-/- mice, and the longevity of
      hematopoiesis and extent of adipogenesis in the supportive hematopoietic
      microenvironment were compared to those from cultures of control, Smad3+/+ or
      heterozygous Smad3+/- mice. MATERIALS AND METHODS: Long-term bone marrow cultures
      (LTBMCs) were established from Smad3+/+, Smad3+/-, or Smad3-/- mice. On a weekly
      basis, the number of cobblestone islands, number of nonadherent cells, confluence
      of the adherent cells, or CFU-GEMM colonies was determined. Bone marrow stromal
      cell lines were established and cobblestone island production on these cell lines
      determined in the presence of nonadherent cells from week-42 Smad3-/- or week-4
      C57BL/6J LTBMCs. RESULTS: Initial proliferative capacity of the LTBMCs was
      similar in all groups through week 20, at which time there was an increase in
      cobblestone islands and production of nonadherent cells and CFU-GEMM colonies in
      the Smad3-/- group. By week 28, only the Smad3-/- LTBMCs had significantly
      maintained increased production of these parameters. Maintenance of cobblestone
      islands indicative of the most primitive hematopoietic progenitor cells persisted
      past 45 weeks in Smad3-/- cultures. The Smad3-/- stromal cell line also
      demonstrated increased support of cobblestone island production when incubated
      with nonadherent cells from week-42 Smad3-/- or week-4 C57BL/6J LTBMCs.
      Evaluation of adipocytogenesis in stromal cells showed significantly greater
      accumulation of adipocytes in lines from Smad3-/- than from Smad3+/+ mice.
      CONCLUSIONS: These data provide evidence for a significant effect of deletion of
      the Smad3 signaling pathway in increased hematopoiesis in LTBMCs and support the
      negative regulatory influence of TGFbeta signaling on adipocytogenesis and long
      term hematopoiesis in vitro.

PMID- 15730860
TI  - Role of VLA-4 and VLA-5 in ex vivo maintenance of human and pig hematopoiesis in
      human stroma-supported long-term cultures.
AB  - OBJECTIVE: The advantage of recipient hematopoiesis over that of xenogeneic
      donors poses a fundamental obstacle to the induction of xenograft tolerance
      through mixed hematopoietic chimerism. Here we explore the role of beta1
      integrins in maintenance of human vs porcine hematopoiesis within a human
      hematopoietic environment. METHODS: Porcine and human c-kit+ bone marrow cells
      were purified and cultured on human bone marrow stroma for 6 weeks. The role of
      VLA-4 and VLA-5 in the maintenance of porcine vs human hematopoiesis in this
      human stroma-supported long-term bone marrow culture (LTBMC) system was evaluated
      by using blocking mAbs that bind to both species. RESULTS: Blocking VLA-4 with
      HP2/1 inhibited both human and porcine hematopoiesis, whereas anti-VLA-5 (SAM-1)
      suppressed the function of human, but not porcine, hematopoietic cells. In mixed
      LTBMC of porcine and human cells on a human stroma, porcine hematopoietic cells
      were at a competitive disadvantage, as seen by a rapid decline in cellularity,
      including clonogenic progenitors. This disadvantage was substantially overcome by
      the addition of SAM-1. Furthermore, human, but not porcine, cell adhesion to
      human fibronectin was inhibited by arginine-glycine-aspartic acid (RGD) peptides.
      CONCLUSION: Taken together, these results indicate that VLA-4 plays critical role
      for porcine hematopoiesis in a human hematopoietic environment, and raise the
      possibility that porcine VLA-5 might be unable to bind the respective human
      ligand and/or to initiate adequate post-ligand-binding signaling. Thus, VLA-5 may
      provide a potential target for developing approaches to improve porcine
      hematopoiesis in human recipients.

PMID- 15730861
TI  - Stable multilineage chimerism across full MHC barriers without graft-versus-host
      disease following in utero bone marrow transplantation in pigs.
AB  - Stable engraftment of hematopoietic progenitors and multilineage chimerism
      following in utero bone marrow transplantation could be a promising modality for
      treatment of prenatally diagnosed blood dyscrasias. For treatment of these
      diseases, stable chimerism in the myeloid and erythroid lineages is important
      because it is anticipated that donor-derived cells will compensate for defects in
      these host lineages. In the present study, a preparation of bone marrow that
      includes fresh, unmanipulated marrow mixed with T-cell-depleted marrow to achieve
      1.5% T-cell content, was injected into the intrahepatic portion of the umbilical
      vein of porcine fetuses at mid-gestation. Donor hematopoietic progenitor cell
      engraftment was assessed in fetal liver and recipient bone marrow postnatally by
      donor-specific polymerase chain reaction of colony-forming units. Chimerism was
      assessed in lymphoid tissues and peripheral blood by flow cytometry. Graft-versus
      host disease (GVHD) was assessed by histological analysis of biopsies of skin,
      bone marrow, liver, and intestine. In this report, we demonstrate that stable
      multilineage chimerism across a full major histocompatibility complex disparity
      can be achieved without GVHD through in utero bone marrow transplantation.

PMID- 15730862
TI  - Effect of altering administration order of busulphan and cyclophosphamide on the
      myeloablative and immunosuppressive properties of the conditioning regimen in
      mice.
AB  - OBJECTIVE: The present study was designed to investigate the influence of the
      administration sequence of busulphan (Bu) and cyclophosphamide (Cy) during
      conditioning regimen on myeloablative and immunosuppressive effects and on
      engraftment. METHODS: Female Balb/C mice were treated with either Bu-Cy or Cy-Bu
      (assigned order of administration). Bu was administered as 8.75 mg/kg/day x 4 and
      Cy as 100 mg/kg/day x 2. The control consisted of untreated animals. Bone marrow
      and spleen were harvested during the conditioning regimen and for up to 19 days
      after treatment. Colony-forming unit granulocyte macrophage assay was performed
      on marrow cells. Immunological analyses were performed using spleen cells. Liver
      status was determined using aspartate amino transferase (AST), alanine amino
      transferase (ALT), and bilirubin. Animals assigned for engraftment study were
      conditioned as above and transplanted using sca-1 cells from male Balb/C donors.
      Engraftment was followed using fluorescence in situ hybridization up to 30 days
      posttransplantation. RESULTS: No significant difference in myeloablative effect
      was observed between treatments. Immunosuppressive activity expressed as
      CD3+/CD19+ and CD4+/CD8+ was also similar. Levels of cytokines interleukin 2,
      tumor necrosis factor alpha, and interferon gamma at the end of the conditioning
      regimen were lower in the Cy-Bu group, while liver enzymes were higher after the
      Bu-Cy regimen. Engraftment in bone marrow was reached faster within the first 20
      days after conditioning with Cy-Bu compared to Bu-Cy. However, no difference in
      chimerism was observed at 30 days. CONCLUSION: Cy-Bu treatment resulted in lower
      levels of cytokines, faster bone marrow engraftment, and lower values of liver
      enzymes compared to Bu-Cy regimen, which may benefit stem cell transplantation
      outcomes.

PMID- 15730863
TI  - Opposing roles for GABAA and GABAC receptors in short-term memory formation in
      young chicks.
AB  - The inhibitory neurotransmitter GABA has both inhibitory and enhancing effects on
      short-term memory for a bead discrimination task in the young chick. Low doses of
      GABA (1-3 pmol/hemisphere) injected into the multimodal association area of the
      chick forebrain, inhibit strongly reinforced memory, whereas higher doses (30-100
      pmol/hemisphere) enhance weakly reinforced memory. The effect of both high and
      low doses of GABA is clearly on short-term memory in terms of both the time of
      injection and in the time that the memory loss occurs. We argue on the basis of
      relative sensitivities to GABA and to selective GABA receptor antagonists that
      low doses of GABA act at GABAC receptors (EC50 approximately 1 microM) and the
      higher doses of GABA act via GABAA receptors (EC50 approximately 10 microM). The
      selective GABAA receptor antagonist bicuculline inhibited strongly reinforced
      memory in a dose and time dependent manner, whereas the selective GABAC receptor
      antagonists TPMPA and P4MPA enhanced weakly reinforced in a dose and time
      dependent manner. Confirmation that different levels of GABA affect different
      receptor subtypes was demonstrated by the shift in the GABA dose-response curves
      to the selective antagonists. It is clear that GABA is involved in the control of
      short-term memory formation and its action, enhancing or inhibiting, depends on
      the level of GABA released at the time of learning.

PMID- 15730864
TI  - Peroxisome proliferator-activated receptors (PPARs) and related transcription
      factors in differentiating astrocyte cultures.
AB  - Peroxisome proliferator-activated receptors (PPARs), retinoid X receptors (RXRs),
      CCAAT/enhancer binding proteins (C/EBPs) and beta-catenin are transcription
      factors involved in cell differentiation. The aim of this work was to investigate
      the occurrence and variations of these proteins during astrocyte differentiation.
      Primary cultures of mouse cortical astrocytes were characterized using nestin,
      A2B5 and glial fibrillary acidic protein (GFAP) as differentiation markers,
      during a period of 21 days in vitro (DIV). Glycogen and triglyceride accumulation
      were also studied. At 3 DIV the cultures were mainly constituted by neural
      progenitor cells, as assessed by their immunofluorescent pattern. At this time
      PPARs and beta-catenin were localized to the cytoplasm. Interestingly, some cells
      contained Oil Red O-positive lipid droplets. Between 7 and 21 DIV, nestin
      decreased, while GFAP increased, indicating ongoing astroglial differentiation.
      beta-catenin, predominantly nuclear at 7 DIV, later localized to membranes.
      Redistribution of all three PPAR isotypes from the cytoplasm to the nucleus was
      observed starting from 7 DIV. Between 7 and 14 DIV, C/EBPalpha, PPARalpha,
      RXRalpha and glycogen content increased. Between 14 and 21 DIV, PPARbeta/delta
      decreased, while PPARgamma, C/EBPbeta and delta and lipid droplet-containing
      cells increased. At 21 DIV both A2B5-/GFAP+ and A2B5+/GFAP+ cells were
      predominantly observed, indicating differentiation toward type-1 and type-2
      astrocytes, although the presence of GFAP- cells demonstrates the persistence of
      neural precursors in the culture even at this time point. In conclusion, our
      results, reporting modifications of PPARs, RXRs, C/EBPs and beta-catenin during
      culture time, strongly suggest the involvement of these transcription factors in
      astrocyte differentiation. Specifically, beta-catenin translocation from the
      nucleus to plasma membrane, together with PPARbeta/delta decrease and C/EBPalpha
      increase, could be related to decreased proliferation at confluence, while
      PPARalpha and gamma and all C/EBPs could participate in differentiation
      processes, such as glycogenesis and lipidogenesis.

PMID- 15730865
TI  - Effects of Na+-Ca2+ exchanger activity on the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolone-propionate-induced Ca2+ influx in cerebellar Purkinje neurons.
AB  - Variations in intracellular calcium activity ([Ca2+]i) play crucial roles in
      information processing in Purkinje neurons such as synaptic plasticity. Although
      Na+-Ca2+ exchanger (NCX) has been shown to participate in the regulation of
      homeostasis and secretion in neuronal cells, the physiological role of NCX in
      Purkinje neurons, such as a role in cerebellar synaptic plasticity, is not well
      understood. NCX in acutely dissociated rat Purkinje neurons was identified by
      double staining with anti-calbindin D-28k antibody and anti-NCX antibody. The
      physiological activity of NCX was examined by measuring transient intracellular
      Ca2+ changes resulting from the Ca2+ influx via reverse mode of NCX (with 0 mM
      Na+/2.5 mM Ca2+ solutions) and the efflux via the forward mode of NCX (with 140
      mM Na+/0 mM Ca2+ solutions). This transient increase in Ca2+ concentration was
      not elicited in the cells pretreated with NCX antisense oligodeoxynucleotides.
      And the Ca2+ influx resulting from the reverse mode of NCX was significantly
      reduced by 2-[2-[4-(4-nitrobenyloxy) phenyl] ethyl] isothiourea methanesulfonate,
      while the Ca2+ efflux via forward mode was inhibited by bepridil. The
      physiological role of NCX in synaptic function was studied by measuring Ca2+
      transients induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolone-propionate
      (AMPA) receptor activation. This AMPA-evoked response was decreased with the
      inhibition of NCX forward mode and also, to less degree, with the inhibition of
      reverse mode. In antisense oligodeoxynucleotides pretreated cells, the AMPA
      evoked response was also reduced, as was the case in NCX-inhibitor treated cells.
      The inhibition of NCX activity had depressant effects on Ca2+ transients induced
      by AMPA receptor activation. These results suggest that NCX plays a physiological
      role in modulating the activity of cerebellar Purkinje neurons, such as synaptic
      plasticity, via interaction with AMPA receptors in Purkinje neurons.

PMID- 15730866
TI  - Single cell analysis of activity-dependent cyclic AMP-responsive element-binding
      protein phosphorylation during long-lasting long-term potentiation in area CA1 of
      mature rat hippocampal-organotypic cultures.
AB  - Phosphorylation of the transcription factor cyclic AMP (cAMP)-response element
      binding protein (CREB) has been implicated in long-term synaptic plasticity and
      memory, and its activation has been proposed to be required for the maintenance
      of long-term potentiation (LTP). The previously described temporal dynamics of
      CREB phosphorylation during the maintenance of LTP showed differences between
      experimental models. In the present study the level of CREB phosphorylation was
      evaluated in organotypic hippocampal slices from young adult rats (P25-30) after
      long-lasting LTP was induced. Immunohistochemistry and confocal imaging were used
      to determine the ratio between non-phosphorylated and phosphorylated CREB at a
      single cell resolution, revealing not only the temporal dynamics but also the
      extent of CREB phosphorylation. The activation of CREB after LTP-induction was
      compared with cAMP-activation after bath application of forskolin. An increase in
      cAMP by forskolin resulted in a persistent, uniform increase of the
      phosphorylated CREB (pCREB/CREB immunofluorescence ratio) in all hippocampal
      principal neurons. In contrast, the induction of long-lasting LTP in CA1 was
      accompanied by a local increase in the pCREB/CREB ratio. Both CREB activation and
      LTP induction in mature cultured slices required N-methyl-D-aspartate (NMDA)
      receptor activation. CREB phosphorylation continued to increase for 4 h during
      LTP maintenance. This sustained activation is in contrast to previous
      observations in acutely prepared slices and supports the hypothesis that CREB
      plays an important role during the late phases of LTP.

PMID- 15730867
TI  - Intraglomerular dendritic link connected by gap junctions and chemical synapses
      in the mouse main olfactory bulb: electron microscopic serial section analyses.
AB  - Glomeruli of the main olfactory bulb are considered to serve as functional units
      in processing the olfactory information. Thus the fine tuning of the output level
      from each glomerulus is important to the information processing in the olfactory
      system. The interactions among neuronal elements in glomeruli might be one of
      main mechanisms regulating this output level. In the mouse main olfactory bulb
      neuronal connections via chemical synapses and gap junction in glomeruli were
      analyzed by the serial electron microscopical reconstruction. Gap junctions were
      encountered between diverse types of dendritic processes, between mitral/tufted
      cell dendrites, between mitral/tufted cell dendrites and periglomerular cell
      dendrites and between mitral/tufted cell dendrites and dendrites of some
      interneurons different from periglomerular cells. Then these morphological
      observations indicate that we must consider both direct coupling between
      mitral/tufted cells via gap junctions and indirect coupling between mitral/tufted
      cells via intervening interneuronal processes. One of gap junction-forming
      processes presynaptic in asymmetrical synapses was traced back to the soma of its
      origin located in the glomerular layer, which was thus identified as an external
      tufted cell. However, interestingly, it showed apparently different
      ultrastructural features from other external tufted cells located at the border
      between the glomerular and external plexiform layers; the latter resemble so
      called mitral/tufted cells located in the external plexiform and mitral cell
      layers. Then external tufted cells were assumed to be heterogeneous in their
      ultrastructural features. We occasionally encountered several dendrites connected
      by gap junctions, which furthermore made chemical synapses with each other and
      with other surrounding processes. Thus both chemical synapses and gap junctions
      interconnect complexly various processes in the glomerulus, where the local
      circuit among intermingled olfactory nerves, mitral/tufted cell dendrites and
      interneuron dendrites is far more complex than previously schematized.

PMID- 15730868
TI  - Immunoreactivity for the group III receptor subtype mGluR4a in the visual layers
      of the rat superior colliculus.
AB  - Several studies indicate that metabotropic glutamate receptors (mGluRs)
      participate in the transmission of visual stimuli in optic layers of the superior
      colliculus (SC). We examined the cellular and subcellular distribution of the
      group III mGluR4a in superficial layers of the rat SC by means of a specific
      antiserum and a preembedding immunogold method for electron microscopy. Deposits
      of mGluR4a immunoparticles were mostly observed on presynaptic membranes of large
      synaptic terminals, which made asymmetrical synapses and contained abundant
      spherical, clear synaptic vesicles and numerous electron translucent
      mitochondria. These characteristic ultrastructural features correspond to
      retinocollicular synaptic terminals. Also, chains of synaptic retinal terminals
      along dendrites were labeled for mGluR4a. About 70% of morphologically identified
      retinal terminals were mGluR4a immunopositive. Furthermore, mGluR4a
      immunoreactivity in SC greatly disappeared following retinal ablation. About 28%
      of cortical terminals identified by anterograde tracing showed mGluR4a labeling,
      whereas only 2% of collicular GABAergic profiles were labeled for mGluR4a. These
      results reveal that retinal terminals are the major contributors to the mGluR4a
      immunoreactivity observed in the superior collicular circuitry.

PMID- 15730869
TI  - Alterations in stress-associated behaviors and neurochemical markers in adult
      rats after neonatal short-lasting local inflammatory insult.
AB  - Recently, there has been a growing interest in long-term consequences of neonatal
      pain because modern neonatal intensive care units routinely employ procedures
      that cause considerable pain and may be followed by local inflammation and
      hyperalgesia lasting for several hours or even days. To address this question, we
      developed a rat model of short lasting (<2 days) early local inflammatory insult
      produced by a single injection of 0.25% carrageenan (CAR) into the plantar
      surface of a hindpaw. Previously, we demonstrated that rats receiving this
      treatment within the first week after birth grow into adults with a global
      reduction in responsiveness to acute pain. Here, we report that these animals
      also manifest a low anxiety trait associated with reduced emotional
      responsiveness to stress. This conclusion is based in the following observations:
      (a) rats in our model display reduced anxiety on an elevated plus-maze; (b) in
      the forced swim test, these rats exhibit behavioral characteristics associated
      with stronger ability for stress coping; and (c) these animals have reduced basal
      and stress-induced plasma levels of such stress-related neuroendocrine markers as
      corticotropin-releasing factor, vasopressin, and adrenocorticotrophic hormone. In
      addition, we used DNA microarray and real-time reverse-transcriptase polymerase
      chain reaction to profile long-term changes in gene expression in the midbrain
      periaqueductal gray (PAG; a region involved in both stress and pain modulation)
      in our animal model. Among the affected genes, serotonergic receptors were
      particularly well represented. Specifically, we detected increase in the
      expression of 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT4 receptors. Several of
      these receptors are known to be involved in the anxiolytic and analgesic activity
      of the PAG. Finally, to determine whether neonatal inflammatory insult induces
      elevation in maternal care, which may play a role in generating long-term
      behavioral alterations seen in our model, we examined maternal behavior for 3
      days following CAR injection. Indeed, we observed a substantial increase in
      maternal attention to the pups at the time of inflammation, but this increase was
      not without its cost: a period of significant maternal neglect afterward.

PMID- 15730871
TI  - Deletion of N-terminal rapsyn domains disrupts clustering and has dominant
      negative effects on clustering of full-length rapsyn.
AB  - The peripheral muscle membrane protein rapsyn is essential for the formation and
      maintenance of high density acetylcholine receptor aggregates at the
      neuromuscular synapse. Rapsyn is concentrated at synaptic sites and is
      colocalized with acetylcholine receptors from the earliest stages of
      synaptogenesis. Previous studies have shown that recombinant rapsyn expressed in
      heterologous cells forms clusters, and acetylcholine receptors coexpressed with
      rapsyn are colocalized with rapsyn clusters. However, the molecular interactions
      involved in clustering of rapsyn are not well defined. To analyze the process of
      cluster formation by rapsyn we examined the formation of rapsyn clusters and
      complexes using mutant constructs specifically deleted for individual domains of
      rapsyn in the presence and absence of tagged, full-length rapsyn. Specific
      deletions of the tetratricopeptide repeat (TPR) domains 1 and 3 of rapsyn
      abrogated not only clustering of mutant rapsyns, but also, in a dominant negative
      fashion, the clustering of tagged, full-length rapsyn. We also analyzed rapsyn
      protein complexes isolated from cells transfected with tagged and untagged
      rapsyn. Our results show that both tagged and untagged rapsyn are present in
      immunoprecipitates of rapsyn from cotransfected cells, demonstrating that rapsyn
      molecules interact directly or indirectly to form oligomers. Mutants that were
      dominant negatives were also present in complexes containing tagged, full-length
      rapsyn. Together these results indicate that rapsyn forms clusters at the synapse
      by oligomerization, and suggest models for the mechanistic bases of this
      oligomerization via interactions mediated by TPRs 1 and 3.

PMID- 15730870
TI  - The negative cell cycle regulator, Tob (transducer of ErbB-2), is a
      multifunctional protein involved in hippocampus-dependent learning and memory.
AB  - Tob (transducer of ErbB2) is a negative cell cycle regulator with anti
      proliferative activity in the periphery. Using a behavioral screening paradigm to
      look for novel gene functions in the brain, we identified Tob as a brain
      expressed protein involved in learning and memory. Behavioral training of fear
      conditioning triggered a transient elevation of Tob protein, which preceded the
      formation of long-term memory. Functional perturbation of Tob by intra-CA1
      infusion of antisense oligonucleotides in rats impaired spatial learning and
      memory in the Morris water maze and long-term memory for contextual fear
      conditioning, two behavioral paradigms that require the hippocampus. Furthermore,
      long-term potentiation was suppressed by Tob antisense infusion into the CA1
      region. Together, these results indicate that the negative cell cycle regulator
      Tob is a multifunctional protein involved in hippocampus-dependent learning and
      memory.

PMID- 15730873
TI  - Highly selective localization of leukotriene C4 synthase in hypothalamic and
      extrahypothalamic vasopressin systems of mouse brain.
AB  - While leukotriene C4 (LTC4) was originally identified as a potent
      bronchoconstrictor, the compound has versatile biological activities besides
      inflammatory reactions. Although the high content of LTC4 has been reported in
      the hypothalamus and median eminence, the precise localization of the compound
      remained obscure. To elucidate its possible functions in the neuroendocrine
      systems, we determined immunohistochemical localization of LTC4 synthase, a key
      enzyme to produce LTC4 using mouse brains. Light microscopy and confocal laser
      scanning microscopy showed that LTC4 synthase was selectively localized in the
      vasopressinergic magnocellular neurons of the hypothalamic paraventricular,
      supraoptic and suprachiasmatic nuclei and in the retrochiasmatic area, as well as
      in axons that emanated from these neurons to the pars nervosa of the pituitary
      gland. At subcellular level, however, LTC4 synthase and arginine vasopressin
      appeared to localize differently within individual neurons. LTC4 synthase
      immunoreactivity was also observed in the axons of the extrahypothalamic system
      including the bed nucleus of the stria terminalis, lateral habenular nucleus,
      midbrain central gray, medial amygdaloid nucleus and ventral septal area,
      although this immunoreactivity was relatively minor. The other brain regions did
      not contain LTC4 synthase immunoreactivity. The distribution of LTC4 synthase did
      not overlap with that of either oxytocin or luteinizing hormone releasing
      hormone. Therefore, LTC4 is considered to be involved in neural functions of the
      brain magnocellular vasopressinergic system such as water retention. LTC4 may
      also be involved in extrahypothalamic vasopressinergic neural functions including
      the regulation of learning and memory, social recognition memory, sexual and
      aggressive behavior, etc.

PMID- 15730872
TI  - Localization of immunoreactivity for deleted in colorectal cancer (DCC), the
      receptor for the guidance factor netrin-1, in ventral tier dopamine projection
      pathways in adult rodents.
AB  - DCC (deleted in colorectal cancer)-the receptor of the netrin-1 neuronal guidance
      factor-is expressed and is active in the central nervous system (CNS) during
      development, but is down-regulated during maturation. The substantia nigra
      contains the highest level of netrin-1 mRNA in the adult rodent brain, and
      corresponding mRNA for DCC has also been detected in this region but has not been
      localized to any particular neuron type. In this study, an antibody raised
      against DCC was used to determine if the protein was expressed by adult dopamine
      neurons, and identify their distribution and projections. Significant DCC
      immunoreactivity was detected in midbrain, where it was localized to ventrally
      displaced A9 dopamine neurons in the substantia nigra, and ventromedial A10
      dopamine neurons predominantly situated in and around the interfascicular
      nucleus. Strong immunoreactivity was not detected in dopamine neurons found
      elsewhere, or in non-dopamine-containing neurons in the midbrain. Terminal fields
      selectively labeled with DCC antibody corresponded to known nigrostriatal
      projections to the dorsolateral striatal patches and dorsomedial shell of the
      accumbens, and were also detected in prefrontal cortex, septum, lateral habenular
      and ventral pallidum. The unique distribution of DCC-immunoreactivity in adult
      ventral midbrain dopamine neurons suggests that netrin-1/DCC signaling could
      function in plasticity and remodeling previously identified in dopamine
      projection pathways. In particular, a recent report that DCC is regulated through
      the ubiquitin-proteosome system via Siah/Sina proteins, is consistent with a
      potential involvement in genetic and sporadic forms of Parkinson's disease.

PMID- 15730874
TI  - Histaminergic modulation of excitatory synaptic transmission in the rat
      basolateral amygdala.
AB  - The effects of histamine on excitatory synaptic transmission between the external
      capsule and basolateral amygdala (BLA) were examined using intracellular and
      field potential recordings in rat amygdala slices. Bath application of histamine
      (20 microM) suppressed intracellular excitatory postsynaptic potentials (EPSPs;
      70.3+/-5.1% of control amplitude) in 43 of 64 BLA neurons, and potentiated EPSPs
      (341+/-81% of control amplitude) in 21 neurons, without changing resting membrane
      potential or input resistance. The histamine-induced suppression of EPSPs was
      accompanied by an increase in paired-pulse facilitation of the slopes of EPSPs,
      suggesting a presynaptic locus of the action. The suppressive effect could be
      blocked by the selective H3 antagonist thioperamide, and mimicked by the
      selective H3 agonist R-alpha-methylhistamine, indicating that the suppressive
      effect is mediated by the presynaptic H3 receptor. The potentiating effect of
      histamine on EPSPs was not accompanied by the change of paired-pulse facilitation
      and was not affected by the presence of H1, H2 or H3 receptor antagonists. In
      addition, the effective concentration of agonist to produce 50% of maximal
      response (EC50) of the potentiating action of histamine is 49 nM, much lower than
      the EC50 (470 nM) of the H3 receptor-mediated suppressive effect characterized
      here. These observations suggest a novel, high affinity and postsynaptically
      mediated effect of histamine. In extracellular recordings, histamine, at low
      concentration (200 nM), consistently potentiated field potentials. At high
      concentration (20 microM), histamine suppressed field potentials, but potentiated
      field potentials when H3 receptors were blocked. Taken together, these results
      revealed that histamine, via the presynaptic H3 receptor and a currently unknown
      mechanism, decreases or increases excitatory synaptic transmission in the BLA
      respectively. This specific histaminergic modulation of neuronal activity in the
      amygdala may play an important role in amygdala-mediated physiological and
      pathophysiological processes, such as fear, emotional learning and memory,
      temporal lobe epilepsy, and affective disorders.

PMID- 15730875
TI  - Spinal distribution and metabolism of 2'-O-(2-methoxyethyl)-modified
      oligonucleotides after intrathecal administration in rats.
AB  - Intrathecal (IT) delivery of antisense oligodeoxynucleotides (ASO) has been used
      to study the function of specific gene products in spinal nociception. However, a
      lack of systematic studies on the spinal distribution and kinetics of IT ASO is a
      major hurdle to the utilization of this technique. In the present study, we
      injected rats IT with 2'-O-(2-methoxyethyl) modified phosphorothioate ASO (2'-O
      MOE ASO) and examined anatomical and cellular location of the ASO in the spinal
      cord and dorsal root ganglia (DRG) by immunocytochemistry. At 0.5 h after a
      single IT injection, immunostaining for ISIS 13920 (a 2'-O-MOE ASO targeting h
      ras) localized superficially in the lumbar spinal cord, while at 24 h the
      immunostaining was distributed throughout the spinal cord and was predominantly
      intracellular. Double staining with cell type specific antibodies indicated that
      the ASO was taken up by both glia and neurons. ASO immunoreactivity was also
      observed in DRG after IT ISIS 13920. Capillary gel electrophoresis analysis
      showed that ISIS 22703, a 2'-O-MOE ASO targeting the alpha isozyme of protein
      kinase C (PKC), remained intact in spinal cord tissue and cerebrospinal fluid up
      to 24 h after the injection and no metabolites were detected. In contrast, after
      IT ISIS 11300, an unmodified phosphorothioate ASO with the same sequence as ISIS
      22703, no full-length compound was detectable at 24 h, and metabolites were seen
      as early as 0.5 h. IT treatment with ISIS 22703 at doses that effectively down
      regulated PKCalpha mRNA in spinal cord did not affect the mRNA expression in DRG.
      In summary, 2'-O-MOE ASO displayed high stability in spinal tissue after IT
      delivery, efficiently distributed to spinal cord, and internalized into both
      neuronal and non-neuronal cells. ASO are able to reach DRG after IT delivery;
      however, higher doses may be required to reduce target gene in DRG as compared
      with spinal cord.

PMID- 15730877
TI  - Immunolocalization of retinoic acid receptors in the mammalian olfactory system
      and the effects of olfactory denervation on receptor distribution.
AB  - All-trans retinoic acid (ATRA), a metabolite of vitamin A, binds to retinoic acid
      receptors (RARs) to mediate gene transcription in target cells. We previously
      found that an ATRA supplement enhanced olfactory recovery rate in adult mice
      after olfactory bulb deafferentation. In this study, we examined the cellular
      localization of RARalpha, RARbeta, and RARgamma and the effects of surgery and
      ATRA treatment using immunocytochemistry. Mice received a left olfactory nerve
      transection with the right side serving as internal control. One day after
      surgery, the mice were given either ATRA mixed with sesame oil or just sesame
      oil. In the unoperated olfactory bulb, only RARalpha immunoreactivity (ir) was
      observed. In the unoperated right olfactory epithelium, RARalpha-ir was found in
      flask-shaped cells located in the supporting cell layer, in cell clusters above
      the basal cell layer, in cells in the lamina propria, in some respiratory cells
      and in the olfactory bulb. The flask-shaped cells did not immunostain for either
      neurons or sustentacular cells. RARbeta-ir was localized only in the respiratory
      cells while no RARgamma-ir was observed in the olfactory epithelium. The density
      of RARalpha-ir cells was higher in the operated left olfactory epithelium and
      highest after ATRA treatment. This study demonstrates the presence of RARs in the
      olfactory system, provides additional support that the ATRA-signaling pathway may
      be involved in the recovery of the olfactory epithelium after injury, and
      suggests a role for an unstudied cell type in that process.

PMID- 15730876
TI  - 5-Hydroxytryptamine action in the rat olfactory bulb: in vitro
      electrophysiological patch-clamp recordings of juxtaglomerular and mitral cells.
AB  - The olfactory bulb, first relay of olfactory pathways, is densely innervated by
      serotoninergic centrifugal fibers originating from the raphe nuclei. Although
      serotonin innervation was reported to be involved in olfactory learning in
      mammals, the action of this neurotransmitter on its putative cellular targets has
      been never described through unitary recordings. This lack of data initiated the
      present study where the effects of 5HT on juxtaglomerular and mitral cells are
      analyzed using whole-cell recordings on olfactory bulb slices. Serotonin
      depolarizes 34% of 525 JG cells. A multivariate statistical analysis of
      juxtaglomerular cells characteristics shows that the serotonin responsive cell
      group can be individualized regarding their tonic discharge-mode in response to a
      direct current injection, their lower expression of hyperpolarization-activated
      cation current and their low membrane capacities. The use of ion channel blockers
      and ramp voltage protocol indicate that serotoninergic depolarization of
      juxtaglomerular cells may be due to a nonselective cation current with a reversal
      potential of -44 mV. Pharmacological tests with serotonin receptor antagonists
      and agonists reveal that 5HT action on juxtaglomerular cells would be mainly
      mediated by 5HT2C receptors. In mitral cells, serotonin acts on 49.1% of the 242
      tested cells, inducing two types of responses. A first subset of mitral cells
      (26.8%, n=65) were hyperpolarized by serotonin. This response would be indirect
      and mediated by action of GABA on GABAA receptors since it was antagonized by
      bicuculline. The involved GABAergic neurons are hypothesized to be
      juxtaglomerular and granular cells, on which serotonin would act mainly via 5HT2C
      and via 5HT2A receptors respectively. The second subset of mitral cells (22.3%,
      n=54) were directly depolarized by serotonin acting through 5HT2A receptors. Our
      data on serotonin action on juxtaglomerular cells and mitral cells reveal a part
      of functional mechanisms whereby serotonin can act on olfactory bulb network.
      This is expected to enrich the understanding of its determining role in olfactory
      learning.

PMID- 15730878
TI  - Distinct roles of glycinergic and GABAergic inhibition in coordinating locomotor
      like rhythms in the neonatal mouse spinal cord.
AB  - The primary objective of our study was to examine the role of the inhibitory
      neurotransmitters glycine and GABA in modulating spontaneous activity and
      coordinating neurochemically induced locomotor-like rhythms in the mouse spinal
      cord. Motor outputs were recorded in lumbar ventral roots of 1-4-day old neonatal
      mice, and the function of glycinergic and GABAergic synapses in regulating
      spontaneous and induced activities was examined by suppressing synaptic
      inhibition using selective glycine or GABAA receptor antagonists. Strychnine (0.5
      microM), a glycine receptor antagonist, did not change the pattern of spontaneous
      activity that consisted of random single spikes and discharges of variable
      durations and intervals. In contrast, blocking GABAA receptors with either
      picrotoxin (10 microM) or bicuculline (5 microM) triggered bilaterally
      synchronous, non-rhythmic discharges. These findings suggested that GABAergic
      synapses suppressed excitatory synapses, and their disinhibition synchronized
      spontaneous discharges between the two sides of the spinal cord. Locomotor-like
      rhythms alternating between the two sides of the spinal cord were triggered by
      the neurotransmitter agonists 5-HT, N-methyl-D,L-aspartic acid and dopamine.
      Blocking glycine receptors increased tonic discharges, and in most preparations
      it reduced the phase correlation between the alternating rhythms. Inhibiting
      GABAA receptor-mediated synapses synchronized the onset and prolonged the
      duration of rhythmic discharges. Intraburst alternating peaks were evident and
      those were suppressed by strychnine, suggesting that they were mediated via
      glycinergic synapses. Our findings indicated that GABAergic and glycinergic
      synapses played different roles in modulating neurochemically induced locomotion
      rhythms. GABAergic inhibition regulated the onset and duration of neurochemically
      induced locomotor-like rhythms, and glycinergic inhibition stabilized the pattern
      of the alternating rhythms.

PMID- 15730879
TI  - Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c
      fos expression.
AB  - Rodent seizure models have significantly contributed to our basic understanding
      of epilepsy. However, medically intractable forms of epilepsy persist and the
      fundamental mechanisms underlying this disease remain unclear. Here we show that
      seizures can be elicited in a simple vertebrate system e.g. zebrafish larvae
      (Danio rerio). Exposure to a common convulsant agent (pentylenetetrazole, PTZ)
      induced a stereotyped and concentration-dependent sequence of behavioral changes
      culminating in clonus-like convulsions. Extracellular recordings from fish optic
      tectum revealed ictal and interictal-like electrographic discharges after
      application of PTZ, which could be blocked by tetrodotoxin or glutamate receptor
      antagonists. Epileptiform discharges were suppressed by commonly used
      antiepileptic drugs, valproate and diazepam, in a concentration-dependent manner.
      Up-regulation of c-fos expression was also observed in CNS structures of
      zebrafish exposed to PTZ. Taken together, these results demonstrate that
      chemically-induced seizures in zebrafish exhibit behavioral, electrographic, and
      molecular changes that would be expected from a rodent seizure model. Therefore,
      zebrafish larvae represent a powerful new system to study the underlying basis of
      seizure generation, epilepsy and epileptogenesis.

PMID- 15730880
TI  - Behavioral responses to injections of muscimol into the subthalamic nucleus:
      temporal changes after nigrostriatal lesions.
AB  - Changes in cellular activity in the subthalamic nucleus are a cardinal feature of
      Parkinson's disease and occur in rodents after lesions of the nigrostriatal
      pathway, a model of Parkinson's disease. GABA-ergic neurons from the globus
      pallidus provide a major input to the subthalamic nucleus. Previous
      electrophysiological studies revealed temporal changes in the activity of
      pallidal neurons after nigrostriatal lesions in rats. However, little is known
      about the impact of these changes on GABAergic transmission in the subthalamic
      nucleus. We have examined the behavioral responses to a local administration of
      the GABA A agonist muscimol into the subthalamic nucleus. Muscimol (0.01 and 0.1
      microg) induced orofacial dyskinesia in normal rats; this response was blunted 2
      weeks but enhanced 2 months after a unilateral lesion of the nigrostriatal
      pathway. The early decrease in the behavioral response occurred at a time when
      increased expression of mRNA for glutamic acid decarboxylase, the enzyme of GABA
      synthesis, and burst firing have been reported in the globus pallidus, suggesting
      an adaptive post-synaptic response to increased GABAergic transmission in the
      subthalamic nucleus. In contrast, we now show that glutamic acid decarboxylase
      mRNA is unchanged in the globus pallidus at the later time point, when
      electrophysiological changes also subside in this region. The increased
      behavioral response at this later time point may reflect a decreased activity in
      GABAergic inputs to the subthalamic nucleus. The results show time-dependent
      changes in behavioral responses to GABA A receptor stimulation in the subthalamic
      nucleus which may reflect adaptive changes in postsynaptic inhibitory responses
      after dopaminergic lesions.

PMID- 15730881
TI  - Ionizing radiation-induced damage on developing cerebellar granule cells cultures
      can be prevented by an early amifostine post-treatment.
AB  - Developing central nervous system (CNS) is highly sensitive to ionizing radiation
      due, in part, to reactive oxygen species (ROS) damage. A variety of compounds
      able to protect brain cells essentially by decreasing ROS production have been
      widely used to confirm ROS participation in different mechanisms of brain injury,
      as well as to evaluate them as therapeutic tools. To test if ionizing radiation
      induced damage on immature cerebellar granule cells is mainly mediated by ROS
      accumulation, a free radical scavenger--amifostine (amf)--was used in an in vitro
      model. Moreover, the amf therapeutic effect was investigated. Results show that
      only an early (20-30 min) post-treatment with amf, acting through an antioxidant
      mechanism, has been effective in preventing cerebellar granule cell loss observed
      after ionizing radiation exposure in vitro. These data suggest that immature
      cerebellar granule cells grown in vitro are highly vulnerable to ROS damage and
      that a therapeutic intervention could be effective in a narrow temporal window.
      Moreover, radiation-induced cell death can be partially prevented by a complete
      limitation of ROS generation, suggesting that other mechanisms besides oxidative
      stress would also be responsible for the cellular damage found in this model.

PMID- 15730882
TI  - Glial-derived nexin, a differentially expressed gene during neuronal
      differentiation, transforms HEK cells into neuron-like cells.
AB  - Glial-derived nexin (GDN) is a proteinase inhibitor secreted from glial cells and
      it can enhance neuronal function. However, its expression and function in
      neuronal differentiation are not, as yet, well-known. In the present study, we
      analyzed glial-derived nexin gene expression in dissociated neural
      stem/progenitor cells (NS/PCs) (D0) from the embryonic mouse cerebral cortex,
      expanded NS/PC cultures (D4 and D10 cultures) and cultured neurons (E15) using a
      semi-quantitative RT-PCR assay. Our data suggest that mouse GDN, homologue of
      human GDN, was significantly up-regulated in the expanded NS/PC cultures and
      cultured neurons. To analyze its function in neuronal differentiation, human GDN
      cDNA was cloned into bicistronic plasmids containing green fluorescent protein
      (GFP) and the resulting plasmids were transfected into rodent primary NS/PCs and
      non-neuronal human embryonic kidney (HEK) cells. Our data suggest that the
      ectopic expression of human GDN triggered the expression of the neuronal marker
      TuJ1 in both NS/PCs and HEK cells. We conclude that GDN is up-regulated during
      neuronal differentiation and plays a role in transforming non-neuronal HEK cells
      into neuron-like cells.

PMID- 15730883
TI  - Ultraviolet- and short-wavelength cone contributions alter the early components
      of the ERG of young zebrafish.
AB  - The electroretinogram (ERG) is a commonly used measure to examine retinal
      processing in both basic and clinical research. The purpose of this study was to
      determine the retinal mechanisms responsible for the developmental differences
      found in the zebrafish ERG waveform. The ERG of young zebrafish possesses a
      voltage-negative response to ultraviolet- and short-wavelength stimuli, but not
      to middle- and long-wavelength stimuli; the ERG of adult zebrafish does not
      possess this response component. ERGs were obtained from young zebrafish before
      and after the introduction of either aspartate, or a combination of APB (DL-2
      amino-4-phosphonobutyric acid) and PDA (cis-2,3-piperidinedicarboxylic acid) in
      order to suppress the responses of various types of retinal neurons. Log
      irradiance versus response amplitude functions of the ERG response to 200-ms
      stimuli of various wavelengths at various times following stimulus onset (70 and
      120 ms) was derived as well as spectral sensitivity. Aspartate eliminated all
      voltage-positive responses regardless of stimulus wavelength; irradiance-response
      functions following aspartate were similar to the early responses of young
      control fish to ultraviolet- and short-wavelength stimuli. APB + PDA produced
      similar but not identical results as aspartate, suggesting that the combination
      of these agents does not completely eliminate all post-receptoral contributions
      to the ERG. Spectral sensitivity functions derived from aspartate-exposed
      subjects at various time measurements were dominated by contributions from
      ultraviolet- and short-wavelength-sensitive cone types. These wavelength
      dependent ERG responses are similar to those found in humans with enhanced S-cone
      syndrome. Finally, ERG waveform differences across stimulus wavelength suggest
      that the circuitry of ultraviolet- and short-wavelength cone types is different
      to that of middle- and long-wavelength cone types in young zebrafish.

PMID- 15730884
TI  - Quantitative analysis of the postnatal development of Purkinje neurons in the
      cerebellum of the cat.
AB  - We have studied the postnatal quantitative changes of cortical Purkinje neurons
      in the cerebellum of the cat at the following postnatal groups of age: P0, P42,
      P72 and adults. An unbiased counting method, the optical fractionator was used
      for the estimation of Purkinje cell numbers. A significant increase of Purkinje
      cell number was found between P0 (1.097 x 10(6)) and P42/P72 (1.805 x 10(6) and
      1.895 x 10(6)) declining to 1.429 x 10(6) in the adult, still 30% higher than in
      the newborn. It was also observed that during the first few postnatal weeks large
      "gaps" were present in the Purkinje monolayer as revealed by Nissl staining and
      metabotropic glutamate receptor 1alpha immunocytochemistry. These Purkinje cell
      gaps were observed most frequently in well-definable areas, especially in the
      intermediate zone of the neocerebellum. Simultaneously with the numerical
      increase of Purkinje neurons between the P0 and P72 age groups, these gaps
      disappeared after the third postnatal week resulting in the completion of the
      Purkinje monolayer in the whole cerebellum.

PMID- 15730885
TI  - Hypothyroidism changes adenine nucleotide hydrolysis in synaptosomes from
      hippocampus and cerebral cortex of rats in different phases of development.
AB  - The influence of the thyroid hormones on the normal function of the mammalian
      central nervous system depends on the brain region and on the developmental
      stage. Adenine nucleotides and their products also affect the brain function; ATP
      is an excitatory neurotransmitter, and adenosine has inhibitory effects on
      neurotransmission. Thus, this study aimed to evaluate the effects of
      hypothyroidism on the hydrolysis of ATP to adenosine in hippocampal and cortical
      synaptosomes and blood serum of rats during different phases of development. Rats
      aged 60 and 420 days old were divided into three groups: control, sham-operated
      and hypothyroid. Hypothyroidism was induced in these rats by thyroidectomy and
      methimazole (0.05%) added to their drinking water for 14 days. Neonatal
      hypothyroidism was induced by adding 0.02% methimazole in the drinking water from
      day 9 of gestation, and continually until 14 days old. Hypothyroidism increased
      the AMP hydrolysis in both hippocampus and cerebral cortex synaptosomes of rats
      in all aged tested. In blood serum, thyroid hormones deficiency increased the AMP
      hydrolysis in 14-day-old rats and the hydrolysis of ATP, ADP and AMP in 60-day
      old rats; however, no alteration was observed in 420-day-old rats. Thus, our
      results suggest the involvement of the 5'-nucleotidase in synaptic function
      control in hypothyroidism throughout brain development.

PMID- 15730886
TI  - Developmental profile of NTPDase activity in synaptic plasma membranes isolated
      from rat cerebral cortex.
AB  - In the present study the developmental profile of ATP-hydrolyzing activity
      promoted by NTPDase 1, its kinetic properties and the enzyme protein abundance
      associated with synaptic plasma membrane from rat cerebral cortex were
      characterized. NTPDase 1 activity increased from birth to day 30; afterwards it
      decreased and remained unchanged from adulthood (90 days) to senescence (365
      days). Kinetic analysis revealed that enzyme exhibited the highest specific
      activity at day 30 and highest apparent affinity for ATP at day 365; however,
      V(max)/K(m) values remained unchanged for each age studied. Immunoblot analysis
      demonstrated that relative abundance of NTPDase 1 is highest at day 15 during
      ontogeny. The discrepancy between maximum enzyme activity and maximum enzyme
      protein abundance indicates that NTPDase 1 may have an additional role during
      development.

PMID- 15730887
TI  - PKC isoforms were reduced by lead in the developing rat brain.
AB  - A plethora of protein kinase C (PKC) isoforms play important roles in regulating
      synaptic plasticity and neurotransmitter release. Even though, most PKC isoforms
      are involved in Pb-induced neuronal toxicity, its mechanism is still unclear. The
      current study addresses the effect of Pb on PKC isoforms in different regions of
      the developing rat brain. Sprague-Dawley (SD) pregnant rats were exposed to 0.1%
      Pb as lead acetate dissolved in distilled deionized water (DDW) from gestation
      day 6 through 21 postnatal day (PND). Control rats were allowed to drink DDW.
      Pups were sacrificed on PND 1, 5, 10 and 45. Rat brain was immediately excised
      and separated into the brain stem (BS), the cerebellum (CB), the hippocampus (HC)
      and the frontal cortex (FC). The Pb level in different regions of the brain was
      determined using an analytical graphite tube atomizer (Varian). Typical PKC
      (alpha, beta, gamma), novel PKC (epsilon) and atypical PKC (mu) in the above
      brain regions were enriched by immunoprecipitation and later were assayed by
      Western blotting. The total, calcium-dependent and -independent PKC activities
      were determined by the radioactivity of total gamma-32P transferred to histone.
      The results indicated that on PND 1, Pb reduced the PKC-gamma protein in HC and
      FC, whereas on PND 5 the proteins of PKC isoforms (alpha, beta, gamma, epsilon,
      mu) in HC and FC were significantly reduced. These reductions in PKC proteins
      were higher in membrane fractions than in cytosolic fractions. On PND 10, Pb
      reduced all PKC isoforms. However, on PND 45, Pb had no significant effect on all
      PKC isoforms except epsilon. Pb inhibited the total PKC activity by 70% on PND 1
      and 5, the bulk of these PKC activities were calcium-dependent. The results
      suggest that during early stages of the rat brain development, Pb exposure
      decreased PKC activities and also reduced PKC isoforms including PKC-gamma and
      epsilon which are reported to have roles in the memory formation and long-term
      potentiation (LTP).

PMID- 15730888
TI  - Maturation of cultured hippocampal slices results in increased excitability in
      granule cells.
AB  - The preparation of hippocampal slices results in loss of input neurons to dentate
      granule cells, which leads to the reorganization of their axons, the mossy
      fibers, and alters their functional properties in long-term cultures, but its
      temporal aspects in the immature hippocampus are not known. In this study, we
      have focused on the early phase of this plastic reorganization process by
      analyzing granule cell function with field potential and whole cell recordings
      during the in vitro maturation of hippocampal slices (from 1 to 17 days in vitro,
      prepared from 6 to 7-day-old rats), and their morphology using extracellular
      biocytin labelling technique. Acute slices from postnatal 14-22-day-old rats were
      analyzed to detect any differences in the functional properties of granule cells
      in these two preparations. In field potential recordings, small synaptically
      evoked responses were detected at 2 days in vitro, and their amplitude increased
      during the culture time. Whole cell voltage clamp recordings revealed intensive
      spontaneous excitatory postsynaptic currents, and the susceptibility to stimulus
      evoked bursting increased with culture time. In acutely prepared slices, neither
      synaptically-evoked responses in field potential recordings nor any bursting in
      whole cell recordings were detected. The excitatory activity was under the
      inhibitory control of gamma-aminobutyric acid type A receptor. Extracellularily
      applied biocytin labelled dentate granule cells, and revealed sprouting and
      aberrant targeting of mossy fibers in cultured slices. Our results suggest that
      reorganization of granule cell axons takes place during the early in vitro
      maturation of hippocampal slices, and contributes to their increased excitatory
      activity resembling that in the epileptic hippocampus. Cultured immature
      hippocampal slices could thus serve as an additional in vitro model to elucidate
      mechanisms of synaptic plasticity and cellular reactivity in response to external
      damage in the developing hippocampus.

PMID- 15730889
TI  - Behavioral and cellular consequences of increasing serotonergic activity during
      brain development: a role in autism?
AB  - The hypothesis explored in this review is that the high levels of serotonin in
      the blood seen in some autistic children (the so-called hyperserotonemia of
      autism) may lead to some of the behavioral and cellular changes also observed in
      the disorder. At early stages of development, when the blood-brain Barrier is not
      yet fully formed, the high levels of serotonin in the blood can enter the brain
      of a developing fetus and cause loss of serotonin terminals through a known
      negative feedback function of serotonin during development. The loss of serotonin
      innervation persists throughout subsequent development and the symptoms of autism
      appear. A review of the basic scientific literature on prenatal treatments
      affecting serotonin is given, in support of this hypothesis, with an emphasis on
      studies using the serotonin agonist, 5-methoxytryptamine (5-MT). In work using 5
      MT to mimic hyperserotonemia, Sprague-Dawley rats are treated from gestational
      day 12 until postnatal 20. In published reports, these animals have been found to
      have a significant loss of serotonin terminals, decreased metabolic activity in
      cortex, changes in columnar development in cortex, changes in serotonin
      receptors, and "autistic-like" behaviors. In preliminary cellular findings given
      in this review, the animals have also been found to have cellular changes in two
      relevant brain regions: 1. Central nucleus of the amygdala, a brain region
      involved in fear-responding, where an increase in calcitonin gene related peptide
      (CGRP) was found 2. Paraventricular nucleus of the hypothalamus, a brain region
      involved in social memory and bonding, where a decrease in oxytocin was found.
      Both of these cellular changes could result from loss of serotonin innervation,
      possibly due to loss of terminal outgrowth from the same cells of the raphe
      nuclei. Thus, increased serotonergic activity during development could damage
      neurocircuitry involved in emotional responding to social stressors and may have
      relevance to the symptoms of autism.

PMID- 15730890
TI  - Long-lasting effects of serotonin deficiency on differentiating peptidergic
      neurons in the rat suprachiasmatic nucleus.
AB  - Serotonin (5-HT, 5-hydroxytryptamine) is known to be an inductor of the brain
      development [Whitaker-Azmitia, P.M., Druse, M., Walker, P., Lauder, J.M., 1996.
      Serotonin as a developmental signal. Behav. Brain Res. 73, 19-29; Ugrumov, M.V.,
      1997. Hypothalamic monoaminergic systems in ontogenesis: development and
      functional significance. Int. J. Dev. Biol. 41, 809-816]. This study was aimed to
      test whether it provides long-lasting effects on the differentiating vasoactive
      intestinal polypeptide (VIP) and vasopressin (VP) neurons of the suprachiasmatic
      nucleus (SCN) in rats. To this aim, 5-HT was depleted in fetal brain by daily
      injections of p-chlorophenylalanine (pCPA), an inhibitor of 5-HT synthesis, to
      pregnant rats from the 13th to the 21st day of gestation. Pregnant rats injected
      with saline served as controls. The offsprings (males) of pCPA-treated and
      control pregnant rats were maintained after birth for two months under normal
      laboratory conditions. Then, the SCN was processed for immunocytochemistry of VIP
      and VP and in situ hybridization of appropriate mRNAs. There were no differences
      in concentrations of VIP and VP mRNAs in the SCN in adult offsprings of the 5-HT
      depleted pregnant rats compared to the controls. Moreover, 5-HT deficiency did
      not induce any change in size of VIP-immunoreactive (IR) and VP-IR neurons.
      Conversely, both the numbers of VIP- and VP-immunoreactive neurons and
      concentrations of the peptides in cell bodies increased significantly. It is
      concluded that 5-HT provides long-lasting effects on differentiating VIP and VP
      neurons in the SCN resulting in attenuated release rather than elevated synthesis
      of both peptides in adulthood.

PMID- 15730891
TI  - The effect of neonatal handling on adult feeding behavior is not an anxiety-like
      behavior.
AB  - Brief periods of handling during the neonatal period have been shown to have
      profound and long-lasting physiological consequences. Previous studies performed
      in our laboratory have demonstrated that handling the pups during the neonatal
      period leads to increased sweet food ingestion in adult life. The objective of
      this study is to verify if this effect could be explained by the enhanced anxiety
      levels in these animals. Litters were divided in: (1) intact; (2) handled (10 min
      in an incubator/day) and (3) handled + tactile stimulation (10 min/day).
      Procedures were performed on days 1-10 after birth. When adults, rats were tested
      in the elevated plus maze apparatus, light dark exploration test and open field
      test. They were also tested for sweet food ingestion, being injected with 2 mg/kg
      diazepam or vehicle 60 min before the test. Handling and handling + tactile
      stimulation do not alter performance in the plus maze test, but handled rats
      presented more crossings in the light/dark exploration test and open field (two
      way ANOVA). Females also spent more % time in the open arms in the plus maze and
      more time in the lit compartment in the light/dark test, presenting more
      crossings in both tests. Both treated rats (handled and handled + tactile
      stimulation groups) consumed more sweet food than intact ones (two-way ANOVA).
      When diazepam was injected prior to the measurement of sweet food ingestion,
      there was no effect of the drug. We suggest that handling during the neonatal
      period leads to plastic alterations in the central nervous system of these
      animals, causing an increased ingestion of palatable food in adult life, and this
      alteration does not express an anxiety-like behavior.

PMID- 15730892
TI  - Expression of cell cycle-related proteins in developing and adult mouse
      hippocampus.
AB  - Developmental structuring of brain is the result of a strictly coordinated
      process that involves controlled cell division, neuronal migration and terminal
      differentiation. Neurogenesis occurs generally during embryonic and early
      postnatal stages and will be finished in the mature brain. Once differentiated,
      neurons are incapable of further division but retain the capability of structural
      and functional plasticity. However, there are distinct regions in the adult brain
      of mammals that generate neurons continuously throughout life. Among them, the
      hippocampus, which is known as a region with a high degree of neuroplasticity, is
      of particular interest in the context of adult neurogenesis. In general,
      progression through cell cycle phases is regulated by the sequential expression
      and activation of regulatory proteins like cyclin dependent kinases (cdk),
      cyclins, or cdk inhibitors (cdki). In postmitotic and terminally differentiated
      neurons, cell cycle activity is arrested by enrichment of cdkis. The timing of
      cell cycle exit and neuronal differentiation is likely to be regulated in part by
      cell cycle regulatory proteins. However, the expression of cell cycle markers in
      the postnatal or adult brain is still a matter of controversial debate. In the
      present study, we examined the expression of cdks, cyclins and cdkis within the
      mouse hippocampus at different developmental stages (embryonic days 17, 19;
      postnatal day 11 and adult) using immunohistochemical methods. During the
      prenatal development, cell cycle proteins were localized predominantly in nuclei
      of all presumptive neuronal populations but expression was not restricted to
      proliferative cells. With developmental progression, the subcellular localization
      of most markers was increasingly shifted from nuclear to the cytoplasmic
      compartment. However, even in the adult, cell cycle-related proteins were found
      in terminally differentiated pyramidal and granule neurons. Here, they were
      mainly localized in the perikaryal cytoplasm but only sporadically in neuronal
      nuclei. Occasionally, immunoreactivity was also found in dendrites and mossy
      fibers. The present results suggest that cell cycle arrest and terminal
      differentiation is not necessarily incompatible with the expression of cell cycle
      related markers. Thus, they may have supplementary functions in differentiated
      neurons that might be associated with neuronal plasticity.

PMID- 15730894
TI  - Electroencephalography in neonatal seizures: comparison of a reduced and a full
      10/20 montage.
AB  - This study compares a reduced electrode montage (9 electrodes) with the full
      10/20 electrode montage for the ability to detect and characterize neonatal
      seizures and background electroencephalographic (EEG) characteristics, utilizing
      new digital technology allowing "remontage" of previously acquired records. A
      total of 151 neonatal EEG records were retrospectively and blindly analyzed by
      two readers. Records were first analyzed for seizure number, topography,
      duration, and characteristics of EEG background using the reduced montage, before
      reanalysis with the full montage. One hundred eighty-seven seizures were
      identified in 31 ictal recordings using the full montage. Using the reduced
      montage, 166 seizures were identified in 30 records. The sensitivity and
      specificity of the reduced montage for detecting electrographic seizures was
      96.8% and 100% respectively. In only one patient's record, the single seizure was
      missed altogether. For grading background abnormalities, the sensitivity and
      specificity of reduced montage was 87% and 80%. Although there are inherent
      weaknesses in reduced montages with respect to both underestimation and
      overestimation of seizure number, a nine-electrode reduced montage can be a
      sensitive tool for identification of neonatal seizures and assessment of
      background characteristics of neonatal electroencephalography.

PMID- 15730893
TI  - Recent advances in infant botulism.
AB  - Since infant botulism was first identified three decades ago, our understanding
      of botulinum toxins and the organisms that produce them has grown. A newer
      classification system now recognizes Clostridium baratii and Clostridium
      butyricum along with Clostridium botulinum as causative agents. Recently,
      increasing therapeutic use of botulinum toxins has sparked substantial new
      research into their mechanisms of action. This research, and some case reports
      from infants sickened by unusual botulinum toxins suggest that disease caused by
      different toxin types may result in varying clinical presentations. Perhaps most
      significantly for pediatricians and child neurologists, a specific treatment for
      infant botulism has just been approved. This article reviews the clinical
      presentation, diagnosis, and treatment of infant botulism, including human
      botulism immune globulin, and discusses the various organisms and toxins that
      cause this disease.

PMID- 15730895
TI  - Electroencephalographic patterns in unresponsive pediatric patients.
AB  - To study the occurrence and incidence of various electroencephalographic
      patterns, the electroencephalograms of unresponsive pediatric patients admitted
      to the intensive care unit were analyzed. The interpreters were unaware of the
      patients' clinical diagnoses. A total of 178 electroencephalographic studies
      performed on unresponsive patients were analyzed over a period of 3 years. The
      mean age of the study patients was 7.9 years. Sixty-six patients were less than 1
      year old. The following electroencephalographic patterns were observed: 58
      patients (33%) manifested electroencephalographic patterns consistent with
      nonconvulsive status epilepticus. Of the patients with nonconvulsive status
      epilepticus, 32 patients (18%) had generalized nonconvulsive status epilepticus
      and 26 patients (14%) manifested partial nonconvulsive status epilepticus. The
      remaining 120 patients (67%) manifested diffuse cerebral dysfunction, with the
      majority having severe diffuse cerebral dysfunction. Only 4 patients (2%) had
      triphasic waves, suggesting a metabolic encephalopathy. Thirty-six percent of the
      patients under the age of 1 year had electroencephalographic patterns consistent
      with nonconvulsive status epilepticus. Nonconvulsive status epilepticus is a
      relatively common electroencephalographic pattern in unresponsive pediatric
      patients. Metabolic encephalopathy is uncommon in this patient group.

PMID- 15730896
TI  - Williams syndrome: pediatric, neurologic, and cognitive development.
AB  - This study examines the developmental history of 32 Williams syndrome patients,
      positive to the fluorescence in situ hybridization (FISH) test. The information
      is intended to provide help for early diagnosis and appropriate stimulation of
      these patients. In the sample reported here, only about half of the patients
      referred with presumptive diagnosis were in fact FISH+, indicating that facial
      dysmorphism may not be the most reliable sign for diagnosis. Initial pediatric
      signs are developmental delay and nocturnal irritability. In consultation, facial
      dysmorphies and heart murmur are detected. There is also low birth weight,
      failure to thrive, unsuccessful breastfeeding, and gastroesophageal reflux. All
      these symptoms are strongly suggestive of Williams syndrome. Subsequent steps
      consist of cardiologic studies. Our results indicate that the triad of symptoms
      consisting of infantile hypercalcemia, dysmorphic facies, and supravalvular
      aortic stenosis, which until recently was considered fundamental for Williams
      syndrome diagnosis, is not usually present and does not lead to an early
      diagnosis. Cognitively, these children are characterized by hypersociability,
      hyperacusia, deficient visuoconstructive abilities, attentional deficit and
      hyperactivity, and in some cases, spontaneous musical interests. There are no
      special verbal skills. The results of this study indicate that the concept of
      Williams syndrome patients as language- and musically-gifted is not fully
      accurate.

PMID- 15730897
TI  - Neurologic outcome in children after extracorporeal membrane oxygenation:
      prognostic value of diagnostic tests.
AB  - This report presents the long-term (36 months) neurologic outcome in 12 neonates
      and 9 children who survived after extracorporeal membrane oxygenation and
      attempts to identify its prognostic indicators through a prospective study in the
      pediatric intensive care unit of a university hospital. Outcome assessment,
      neurodevelopmental tests, electroencephalogram, auditory evoked potentials,
      visual evoked potentials, and somatosensory evoked potentials, cerebral
      sonography, or cerebral tomography were evaluated at the end of bypass and at 6,
      12, 24, and 36 months after extracorporeal membrane oxygenation. "Before
      extracorporeal membrane oxygenation" variables (oxygenation index, pH, oxygen
      arterial partial pressure) and "during extracorporeal membrane oxygenation"
      variables (pH, oxygen arterial partial pressure, duration of bypass, clotting
      activated time, electroencephalogram) were also analyzed. A negative neurologic
      outcome (Glasgow Outcome Score different from "good recovery" or
      neurodevelopmental score less than 70) 12 months after extracorporeal membrane
      oxygenation was documented in 8.3% of neonates and in 30% of children who
      survived. There was no further change in subsequent evaluations (24 and 36 months
      follow-up). The most abnormal electroencephalogram during extracorporeal membrane
      oxygenation, the first electroencephalogram, neuroimaging score, and
      somatosensory evoked potentials after extracorporeal membrane oxygenation
      treatment were associated with negative neurologic outcome. The study documented
      that neonates and children treated with extracorporeal membrane oxygenation
      require long-term follow-up; electroencephalogram, neuroimaging score, and
      somatosensory evoked potentials have prognostic value for abnormal neurologic
      outcome.

PMID- 15730898
TI  - Intra-hospital lethality among infants with pyogenic meningitis.
AB  - Predictor variables of intra-hospital lethality among infants with pyogenic
      meningitis due to Neisseria meningitidis, Haemophilus influenzae, and
      Streptococcus pneumoniae were identified using data from a follow-up study of
      infants with bacterial meningitis. The infants who were admitted to Couto Maia
      Hospital from March 1, 1997 to December 31, 1997 presenting with symptoms of
      bacterial meningitis were identified and included in a database. An analysis of
      the clinical and laboratory information was performed using EPI info 6.01b and
      SPSS 6.1 statistical programs. The total mortality rate was 17.1%, and the
      majority of deaths occurred within 48 hours of hospitalization. Factors
      associated most frequently with poor outcome included absence of respiratory
      infection, high cerebrospinal fluid protein, and compromised cranial nerves.
      Early identification of major risk groups is important to adopt measures to
      improve prognosis.

PMID- 15730899
TI  - Heart rate variability and autonomic dysfunction in SSPE.
AB  - Autonomic nervous system involvement in subacute sclerosing panencephalitis was
      studied in 29 patients by analysis of heart rate variability and compared with a
      control group which consisted of 20 age- and sex-matched healthy subjects. Holter
      recordings for 24 hours were obtained, and all recordings were analyzed using
      time-domain parameters. The patients with subacute sclerosing panencephalitis
      were found to have significantly lower values of standard deviation of all normal
      sinus intervals and triangular index when compared with the control group. Of 23
      patients who had regular follow-up, 15 died in a period ranging from 1 to 13
      months. Twelve of these patients had heart rate variability parameters lower than
      normal, but no significant difference was observed between the heart rate
      variability values of patients who survived or died. Also, there was no
      association between brain magnetic resonance imaging findings and heart rate
      variability indices. It is concluded that patients with subacute sclerosing
      panencephalitis have autonomic dysfunction; and this was thought to be mainly due
      to central involvement.

PMID- 15730900
TI  - Electroconvulsive therapy for malignant catatonia in childhood.
AB  - A 13-year-old female is described with presumed viral encephalitis, who developed
      progressive catatonia, agitation, and autonomic dysfunction. The diagnosis of
      malignant catatonia was made, and the patient improved with electroconvulsive
      treatment. This article discusses features, causes, differential diagnosis, and
      treatment of malignant catatonia. In children with this syndrome,
      electroconvulsive treatment should be considered.

PMID- 15730901
TI  - Infant botulism, type F, presenting at 54 hours of life.
AB  - We report a case of botulism in a 54-hour-old infant with rapidly progressive
      fulminant paralysis and rapid spontaneous recovery atypical for infant botulism.
      Clostridium baratii and type F botulinum neurotoxin were isolated from the
      patient's stool. This unique presentation with rapid recovery is consistent with
      pharmacokinetics of type F botulinum neurotoxin. Interestingly, a muscle biopsy
      also revealed pathologic changes early in the disease course. This article
      reports the youngest known case of infant botulism and only the third reported
      case of this disease caused by type F neurotoxin. Botulism should be considered
      in patients of any age with subacute or acute neuromuscular weakness.

PMID- 15730902
TI  - A case of psychosis with temporal lobe epilepsy: SPECT changes with treatment.
AB  - An 8-year-old male was referred to the child psychiatry department because of
      vivid visual and auditory hallucinations, including multiple voices talking to
      each other, and loss of consciousness. Magnetic resonance imaging scans revealed
      cortical dysgenesis in the left inferior frontal cortex and adjacent subcortical
      structures. Single-photon emission computed tomography imaging revealed left
      temporal hypoperfusion. Risperidone therapy was initiated because there was no
      remission after carbamazepine and sodium valproate treatment. After risperidone
      treatment, symptoms remitted. A control single-photon emission computed
      tomography study indicated that the left temporal hypoperfusion was normalized.
      After discontinuation of risperidone, symptoms returned, and
      electroencephalography revealed generalized slow-wave activity particularly
      prominent in the left temporal region. To our knowledge, this is one of the first
      reports of cerebral blood flow changes in a pediatric patient with psychosis
      after treatment.

PMID- 15730903
TI  - Severe lethal spinal muscular atrophy variant with arthrogryposis.
AB  - Spinal muscular atrophies are a clinically and genetically heterogeneous group of
      disorders. Atypical forms of the disease have also been described, including
      those with associated sensory deficits, hearing loss, cerebellar hypoplasia,
      congenital heart defects, arthrogryposis, and bone fractures at birth. The
      patient described here is a male infant, born to a 30-year-old mother at 34 weeks
      of gestation complicated with polyhydramnios. The first son of consanguineous
      parents had died with the same clinical features. The patient required
      ventilatory support because of respiratory failure after the birth and died on
      day 13. His physical examination revealed profound generalized hypotonia, absence
      of deep tendon and neonatal reflexes, dysmorphic facies, arthrogryposis,
      clinodactyly, and left femur fracture. A muscle biopsy revealed variation in
      fiber size with occasional hypertrophic fibers. The postmortem examination
      revealed loss and degeneration of anterior horn cells. We propose that the
      patient, who presented with severe hypotonia, femur fracture, arthrogryposis,
      dysmorphic features, history of early death of his brother with the same clinical
      features and parental consanguinity, had probable X-linked spinal muscular
      atrophy. However, autosomal-recessive inheritance can not be completely excluded.

PMID- 15730904
TI  - Corticosteroid treatment in patients with Sydenham's chorea.
AB  - Sydenham's chorea occurs in approximately 10% of acute rheumatic fever and is one
      of its major manifestations. The disease may last for weeks or months, with a
      high risk of recurrence; usually only supportive treatment is recommended. This
      report describes five children diagnosed with Sydenham's chorea and treated with
      a short course of corticosteroids. Marked improvement of the involuntary
      movements was observed within 24-48 hours, with complete resolution within 7-12
      days after commencement of treatment; there were no relapses. Larger, possibly
      comparative studies are necessary, but in the meantime treatment with
      corticosteroids in patients with Sydenham's chorea should be considered.

PMID- 15730905
TI  - Hemorrhagic stroke in a child with protein S and factor VII deficiencies.
AB  - A 12-year-old previously healthy male, with a family history of protein S
      deficiency, presented with confusion, aphasia, and right upper extremity weakness
      after a 10-day febrile illness. Imaging studies revealed sinovenous thrombosis
      and left parietal hemorrhagic stroke. On further investigation he was found to
      have both protein S and factor VII deficiencies.

PMID- 15730906
TI  - Zoster-associated intracranial hypertension.
AB  - A 14-year-old female presented with headache, vomiting, and a rash. She was found
      to have papilledema and herpes zoster. Examination of the cerebrospinal fluid
      revealed pleocytosis and an elevated protein concentration. Varicella-zoster
      virus deoxyribonucleic acid was detected in the cerebrospinal fluid by polymerase
      chain reaction. Intracranial hypertension was treated by repeated lumbar puncture
      and with acetazolamide. This case represents an unusual complication of the
      reactivation of varicella-zoster virus.

PMID- 15730907
TI  - Focal seizure and cerebral contrast retention after cardiac catheterization.
AB  - Although rare, ionic and nonionic contrast-induced seizures occur as a
      complication of enhanced cranial computed tomography for both adults and
      children. However, contrast-induced seizures after cardiac catheterization has
      only been reported in adults. This report describes an 18-month-old male who
      developed a new-onset focal seizure 12 hours after cardiac catheterization.
      Unenhanced cranial computed tomography 1 hour after the seizure demonstrated
      general cerebral edema and unilateral focal cerebral contrast retention with
      sparing of the area supplied by the middle cerebral artery. The contrast was
      reabsorbed from the subarachnoid space over a 48-hour period, the cerebral edema
      resolved over several days, and the child returned to his baseline state 4 days
      after the seizure episode. This study documents the evolution of computed
      tomographic findings after contrast-induced seizures in a child. Contrast
      toxicity should be considered in any case of a new-onset neurologic deficit
      arising after angiography or enhanced computed tomography.

PMID- 15730909
TI  - The extensor plantar response in neonates is not the same as the Babinski sign.

PMID- 15730910
TI  - Biliary tract complications after liver transplantation.

PMID- 15730911
TI  - Treatment of patients with alcoholic liver disease.
AB  - BACKGROUND: The proportion of alcoholic liver disease among all kinds of liver
      diseases in China is increasing. Recent research has elucidated the mechanisms of
      alcohol-induced liver injury and offered the prospect of advances in the
      management of alcoholic liver disease. DATA RESOURCES: Searching MEDLINE (1982
      July 2004) for papers on alcoholic liver disease, especially those on the
      treatment of alcoholic liver disease. RESULTS: Abstinence remains the cornerstone
      of management of all forms of alcoholic liver disease. Nutritional support
      therapy is also a basal treatment. Corticosteroids may be benefitial for some
      severe alcoholic hepatitis. None of other measures including anti-inflammatory
      agents, antioxidants or colchicine has been shown consistently to improve the
      course of alcoholic liver damage. Ultimately, liver transplantation remains an
      option for selected patients with liver failure due to chronic alcoholic liver
      disease. CONCLUSIONS: Abstinence and nutritional support remain the base
      management of alcoholic liver disease. Corticosteroid is efficient for some
      severe alcoholic hepatitis. Anti-inflammatory agents and antioxidants may be of
      benefit but need further studies. The efficacy of other measures including the
      use of colchicine and propylthiouracil is controversial. Liver transplantation
      remains an option for selected patients with liver failure.

PMID- 15730912
TI  - Inhibitory effect of cyclosporine A on hepatitis B virus replication in vitro and
      its possible mechanisms.
AB  - BACKGROUND: Hepatitis B related end-stage liver disease is recently acknowledged
      as one of the main indications for orthotopic liver transplantation (OLT).
      However, the high recurrence rate of hepatitis B virus infection following
      transplantation is regarded as a major factor affecting the long-term survival of
      transplant recipients especially in China. Cyclosporine A (CsA), which is
      routinely used to prevent the allograft rejection, is reported to have the
      inhibitory activity on hepatitis B virus (HBV) replication in vitro. In this
      paper, we review the inhibitory effect and its possible mechanisms of CsA on HBV
      replication in vitro. DATA RESOURCES: An English-language literature search was
      conducted using MEDLINE (1990-2004) on cyclosporine A, hepatitis B virus,
      mitochondria, calcium and other related reports and review articles. RESULTS:
      Hepatitis B x protein (HBx) is essential to HBV replication. The cytosolic
      calcium signaling mediated by mitochondria and the Src kinase pathway were
      involved during HBx activation of HBV replication. CsA inhibits the HBV
      replication in vitro by its binding to mitochondrial cyclophilin D, then blocking
      the mitochondria-mediated cytosolic calcium signaling. The derivates of CsA also
      have the HBV replication inhibitory effect in vitro. CONCLUSIONS: By interacting
      with mitochondria, preventing the release of intramitochondrial calcium, and then
      blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in
      vitro. The derivates of CsA also have this activity.

PMID- 15730913
TI  - Antibiotic prophylaxia in patients with severe acute pancreatitis.
AB  - BACKGROUND: The prophylactic use of antibiotics in patients with severe acute
      pancreatitis remains contentious. This study was undertaken to review the current
      studies on antibiotic prophylaxis in patients with severe acute pancreatitis.
      DATA RESOURCES: All papers found by a Medline search were relevant to human
      trials of antibiotic prophylaxis in patients with severe acute pancreatitis.
      RESULTS: In the 1970s, three small randomized studies of prophylactic ampicillin
      in the treatment of acute pancreatitis showed no effect on mortality or
      morbidity, but the inclusion of patients at low risk for infection and the use of
      an ineffective antibiotic were insufficient to detect any differences. From 1993
      to 2001, eight prospective clinical trials of antibiotic prophylaxis were
      conducted in patients with severe acute pancreatitis (SAP). Seven of the 8 trials
      showed significant effect of the prophylaxis in prevention of pancreatic
      infections, and one showed significant improvement of clinical course documented
      by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Only
      two trials did demonstrate the significance of the prophylaxis in lowering the
      mortality rate. Despite variations in drug agents, study size and patient
      selection, duration of treatment, and methodology (None of the studies was double
      blinded), a meta-analysis showed the positive effect of antibiotics in reducing
      the mortality. We suggested that antibiotic prophylaxis with proven efficacy in
      necrotic pancreatic tissues should be given to all patients with acute
      necrotizing pancreatitis. In recent years, however, the first double-blind,
      placebo-controlled multicenter study from Germany detected no benefit of
      antibiotic prophylaxis with respect to the risk of developing infected pancreatic
      necrosis. CONCLUSION: Prophylactic antibiotics for severe acute pancreatitis is
      still a matter of discussion and further studies are required to provide adequate
      data to answer many questions and to define the role of antibiotic prophylaxis in
      patients with severe acute pancreatitis.

PMID- 15730914
TI  - Orthotopic liver transplantation for patients with Klatskin tumor.
AB  - BACKGROUND: It is not certain whether Klatskin tumor should be a routine
      indication for orthotopic liver transplantation (OLT). This study was to
      summarize the indication and value of orthotopic liver transplantation for
      patients with Klatskin tumor. METHODS: Forty patients with Klatskin tumors
      including 5 patients who had had liver transplantation (LTx) and 35 patients who
      had not undergone LTx (WLTx) from January 1992 to December 2003 were analyzed
      retrospectively. Their TNM stages were comparable in both groups. In the LTx
      group, 4 patients had Klatskin tumor including recurrent tumor after
      resection(1), and 1 cancerization from Carolis disease. Biliary duct anastomosis
      was made by Roux-en-Y choledochojejunostomy in 2, and end-to-end
      choledochocholedochostomy (C-C) in 3. RESULTS: In the LTx group, the total
      resection rate and radical resection rate were both 100%. Four patients have been
      surviving for 48, 38, 21 and 5 months, respectively, except one died from bile
      leakage at day 40 after transplantation. All 4 survivors enjoyed good life
      without tumors at local and distant sites, even though 2 of these patients
      developed biliary stricture, which was soon resolved by radiological
      intervention. The 1-,3-year survival rates were both 80% in this group. The total
      resection rate and radical resection rate in the WLTx group were 63.0%(17/27)and
      40.7%(11/27)and, the 1-, 3-, 5-year survival rates were 32.2%, 8.0%, 0%,
      respectively. There were significant differences between the two groups in
      radical resection rates and survival rates(P=0.016). CONCLUSIONS: OLT is a good
      choice for patients with unresectable Klatskin tumor by routine modalities. The
      prognosis of patients undergoing OLT is encouraging.

PMID- 15730915
TI  - Multislice spiral CT angiography in evaluation of liver transplantation
      candidates.
AB  - BACKGROUND: Orthotopic liver transplantation has become the treatment of choice
      for patients with end-stage liver disease. This study was designed to study
      whether multislice spiral CT angiography (MSCTA) could be used for preoperative
      evaluation for orthotopic liver transplantation candidates. METHODS: Eighty
      consecutive potential candidates for liver transplantation were evaluated with
      dual-phase three-dimensional CT angiography (3DCTA). The arterial-phase was used
      to create vascular maps of the celiac axis (including the origin of the hepatic
      common artery, left gastric artery and splenic artery) and origin of the superior
      mesenteric artery. The portal venous-phase was used to analyze portal vein
      thrombosis and collateral vascularization of the portal vein. Statistical
      analyses were made using the chi-square test for differences between hepatic
      arterial anatomy of 80 patients and Michel's type I anatomy of 200 patients.
      Appearance of MSCTA and operative results of 16 patients were analyzed. RESULTS:
      Sixty-two patients (77.5%) showed conventional and 18 (22.5%) nonconventional
      hepatic arterial anatomy. A significant difference was found between the two
      groups in anatomy of the hepatic artery (P<0.05). Celiac axis stenosis was
      observed in 6 patients, SA aneurysm in 2, small-caliber hepatic arterial vessels
      in 2, and portal vein thrombosis in 15. Vascular structures of 16 operative
      patients were well defined. CONCLUSION: As a noninvasive examination, MSCTA can
      provide a comprehensive preoperative vascular evaluation for liver
      transplantation candidates.

PMID- 15730916
TI  - Protective effects of glycine pretreatment on brain-death donor liver.
AB  - BACKGROUND: Morphological and functional changes commonly occur in livers of
      brain-death donors. Prevention of liver injury from brain-death will benefit the
      results of transplantation. This study was conducted to evaluate the protection
      effects of glycine on the liver of brain-death donor. METHODS: Fourty-two male
      Wistar rats were randomly divided into brain-death donor (BDD) group (B), glycine
      pretreatment group with BDD (G), and strychnine pretreatment group with BDD(S).
      For these groups, brain death model was established in donor rats and liver
      transplantation was performed subsequently utilizing microsurgical techniques.
      After the establishment of the model and during cold rinsing of liver donors or
      liver reperfusion of recipients, glycine was given at a dose of 0.6 mmol, 25
      micromol and 25 micromol in the group G, and a same dose of glycine and
      strychnine (1000 :1) was prescribed for the group S, but nothing for the group B.
      Before cold rinsing at 2 and 6 hours after portal vein(PV) reperfusion, blood
      samples were taken from infrahepatic vena cava (IHVC) to determine the levels of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis
      factor alpha (TNF-alpha) and hyaluronic acid (HA). At 6 hours after PV
      reperfusion, graft samples were fixed for morphological observation and apoptosis
      of hepatocytes was detected using the TUNEL method. RESULTS: Before liver cold
      rinsing and at 2 and 6 hours after PV reperfusion, the serum levels of ALT, AST,
      TNF-alpha, HA and apoptosis index (AI) in the groups B and S were significantly
      higher than those in the group G (P<0.05). There was no significant difference
      between the groups B and S (P>0.05). Electron microscopy showed that Kupffer
      cells were activated and hepatic cells injured more obviously in the groups B and
      S than in the group G. CONCLUSION: Glycine pretreatment can improve the viability
      of the liver of the brain-death donor rat.

PMID- 15730917
TI  - Correlation of polymorphism in the interleukin-1 receptor antagonist gene intron
      2 with alcoholic liver disease.
AB  - BACKGROUND: Interleukin-1 receptor antagonist (IL-1ra) can inhibit the pro
      inflammatory effects of IL-1, which recently has been thought to involve the
      pathogenesis of alcoholic liver disease (ALD). This study was undertaken to
      determine whether there is any association between IL-1ra gene polymorphism and
      ALD in a Chinese population. METHODS: The polymorphism of IL-1ra gene intron 2
      (VNTR) was assessed in 165 alcoholics (43 alcohol-dependent subjects without
      liver diseases, 30 patients with alcoholic fatty liver, 61 patients with
      alcoholic hepatitis and 31 patients with alcoholic cirrhosis) and 65 healthy
      control subjects by PCR with DNA of peripheral blood mononuclear cells. RESULTS:
      The rate of IL-1RN*1 carriage was statistically higher in the alcoholics than in
      the control group (98.79% vs 93.85%, chi2=4.48, P<0.050). And the IL-1RN*1 allele
      frequency was more common in the alcoholics than in the control group (86.67% vs
      76.92%, chi2=6.56, P<0.025). IL-1RN*1 heterozygote was significantly more
      frequent in the patients with alcoholic hepatitis or those with cirrhosis than in
      the alcohol-dependent subjects without liver diseases (32.79%, 29.03% vs 9.30%;
      chi2=7.84, chi2=4.84; P<0.010, P<0.050). The IL-1RN*2 allele frequency in the
      patients with alcoholic hepatitis and the patients with cirrhosis was also
      significantly higher than in those alcoholics without liver diseases (13.93%,
      17.74% vs 4.65%; chi2=4.79, chi2=6.78; P<0.050, P<0.010). But the frequencies of
      IL-1RN*1 heterozygote and IL-1RN*2 allele appear to be not different between the
      patients with alcoholic fatty liver and the alcoholics without liver diseases.
      CONCLUSIONS: IL-1ra gene polymorphism is closely associated with race. IL-1RN*2
      allele doesn't influence the susceptibility to ALD, but the gene carriers with
      ALD have additional risk for aggravation of the illness.

PMID- 15730918
TI  - Tight association of hepatocellular carcinoma with HBV infection in North China.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cancer in
      China. Hepatitis B and C viruses (HBV and HCV) and aflatoxins are known risk
      factors for HCC, but the etiological status of these factors in HCC development
      is not clear. This study was undertaken to define the absolute importance of HBV
      in hepatocarcinogenesis of North China. METHODS: A consecutive series of 119
      patients with pathologically proven HCC were collected from North China during
      January 1998 to December 2000 by the Cancer Hospital of the Chinese Academy of
      Medical Sciences, Beijing. Serum HBsAg, anti-HBc and anti-HCV were negative HBV
      sero-markers. The HBV X gene was analyzed for its expression by PCR, DNA
      sequencing, and immunohistochemistry. RESULTS: In the 119 HCC patients, 82.4%
      (98/119) were HBsAg seropositive. When a comprehensive set of HBV markers were
      detected, the HBV infection rate in these HCC patients was 99.2% (118/119). Of
      the patients, 11.8%(14/119) were found to be anti-HCV positive. But all the anti
      HCV positive HCC patients were co-infected with HBV. CONCLUSIONS: HBV infection
      is virtually ubiquitous in HCC patients in North China. The tight association of
      HBV with HCC strongly suggests the dominant role of HBV infection in causing
      hepatocellular carcinoma. About 11.8% of HCC patients being HCV-related are co
      infected with HBV.

PMID- 15730919
TI  - Ultrasound-guided fine needle biopsy of intrahepatic nodules and low elevation of
      AFP in early diagnosis of hepatocellular carcinoma.
AB  - BACKGROUND: With the progress in early clinical treatment of hepatocellular
      carcinoma (HCC), early detection and diagnosis of HCC have been increasingly
      pressing. Combined alpha-fetoprotein(AFP) determination and ultrasonography has
      become the main method for the detection of small HCC; but the relationship
      between low elevation of AFP and pathologic findings of small HCC has not been
      well defined. The aim of this study was to assess the value of ultrasound-guided
      fine needle biopsy of intrahepatic nodules and low elevation of serum AFP in the
      early diagnosis of HCC. METHODS: Fifty-nine patients with serum AFP exceeding 20
      ng/ml and intrahepatic nodules varying from 0.8 cm to 5.0 cm in diameter who had
      been detected by ultrasonography underwent ultrasound-guided percutaneous fine
      needle biopsy, and cytological staining and histological sectioning were
      performed at the same time. RESULTS: Among the 59 patients, 11 patients (18.6%)
      showed AFP level above 400 ng/ml, 5 (8.5%) from 200 ng/ml to 400 ng/ml, 18
      (30.5%) from 50 ng/ml to 200 ng/ml and 25 (42.4%) from 20 ng/ml to 50 ng/ml.
      Follow-up demonstrated that 53 patients (89.8%) had a progressive increase of AFP
      level. In 58 patients (98.3%) cancer cells were found by cytological staining
      and/or histological sectioning. CONCLUSIONS: In those patients with slightly
      increased or continuously positive AFP, hepatic carcinoma should be highly
      suspected when AFP increases gradually and intrahepatic nodules are detected by
      ultrasonography in follow-up. Once intrahepatic carcinoma nodules are suspected,
      ultrasound-guided fine needle biopsy should be performed as early as possible for
      early diagnosis and treatment.

PMID- 15730920
TI  - Early enteral and parenteral nutritional support in patients with cirrhotic
      portal hypertension after pericardial devascularization.
AB  - BACKGROUND: The abnormal metabolism caused by cirrhosis always results in a
      complex problem about nutritional support, which will be more intricate while
      patients with portal hypertension are treated with pericardial devascularization.
      Comparing the effects of early enteral and parenteral nutritional support in
      patients with cirrhotic portal hypertension after pericardial devascularization,
      we try to realize the advantages and disadvantages of the two nutritional
      therapies and to guide our clinical practice. METHODS: After pericardial
      devascularization, 40 patients with cirrhotic portal hypertension were divided
      randomly into 2 groups: enteral and parenteral nutritional support, respectively.
      The general nutritional condition, capability of producing protein, liver
      function, blood velocity of the portal vein, gut function, bowel bacterial
      translocation, mortality, complication rate, stay in ICU, duration of
      hospitalization and costs of treatment were determined in all the patients and
      compared between the 2 groups. RESULTS: Both enteral and parenteral nutritional
      supports could improve the general nutrition condition of the patients; but
      patients receiving enteral nutritional support had fewer complications. Enteral
      nutrition was more effective than parenteral nutrition in increasing the blood
      velocity of the portal vein, stimulating gut motion, preventing bowel bacterial
      translocation, shortening the stay in ICU and the duration of hospitalization,
      and saving costs of treatment. CONCLUSION: After pericardial devascularization,
      patients with cirrhotic portal hypertension should be treated with enteral
      nutritional support as early as possible.

PMID- 15730921
TI  - Clinical characteristics and mechanism of liver damage in patients with severe
      acute respiratory syndrome.
AB  - BACKGROUND: Abnormal liver function was found in patients with severe acute
      respiratory syndrome (SARS). This study was undertaken to explore the clinical
      characteristics and mechanisms of liver damage. METHODS: The serial laboratory
      data of liver function test and hepatic histological examination from 168
      patients with SARS were retrospectively analyzed. RESULTS: The abnormalities of
      serum alanine aminotransferase (ALT) were 52.5%, 71.8%, 85.7% and 85.2%. The
      average levels of ALT of the patients were 56.07+/-51.57 U/L, 86.46+/-69.93 U/L,
      106.69+/-102.50 U/L and 111.32+/-160.24 U/L, and the average levels of serum
      albumin were 37.25+/-5.37 g/L, 35.82+/-4.74 g/L, 34.49+/-5.04 g/L, and 34.26+/
      4.70 g/L, at the day of admission, the first week, second week, and third week
      after hospitalization, respectively. Significant correlation was not shown among
      liver damage, blood oxygen saturation (SaO2), degree of fever, and immune
      functional disorder in this study. Hepatic histological examination of 4 patients
      demonstrated that non-specific inflammation existed in the liver. CONCLUSIONS:
      Liver damage of patients with SARS usually occurs in the early stage of the
      disease with a high occurrence rate and a prolonged profile, which can be
      characterized by early, obvious decrease of albumin levels and slightly abnormal
      levels of ALT. The liver damage induced by SARS seems to be caused by SARS virus
      directly rather than by low SaO2 or high fever. Hepatotoxic drugs may play a role
      in increasing the severity of liver damage or prolonging the time of liver
      function recovery.

PMID- 15730922
TI  - Long-term curative effects of combined hepatocholangioplasty with choledochostomy
      through an isolated jejunum passage on hepatolithiasis complicated by stricture.
AB  - BACKGROUND: Hepatocholangioplasty combined with choledochostomy was designed
      through an isolated jejunum passage in 1988. This study was undertaken to
      evaluate its long-term curative effects in 163 patients. METHODS: The 163
      patients with hepatolithiasis complicated by stricture were treated with this
      procedure from 1988 to 2003. RESULTS: Among these patients, 19 patients with
      postoperative hepatolithiasis complicated by acute cholangitis were treated
      successfully with percutaneous paracentesis drainage through the isolated jejunum
      passage and without operation, 36 patients had postoperative residual or
      recurrent stones (35 patients had stones removed through the stoma and one
      underwent relaparotomy because of stenosis of the common bile duct along with
      stone in canceration). The clearance rate of stones after the isolated jejunum
      passage was 97%; 35 patients (21%) complicated with stricture due to hepatolith
      were treated with combined hepatocholangioplasty and choledochostomy. Follow-up
      for 1 to 15 years showed no recurrent stricture of the biliary tract. The
      operation also successfully prevented reflux cholangitis and other serious
      complications after Roux-en-Y cholangio-jejunostomy. CONCLUSION:
      Hepatocholangioplasty combined with choledochostomy through an isolated jejunum
      passage may significantly improve the long-term curative effects of
      hepatolithiasis with stricture.

PMID- 15730923
TI  - Splenocaval versus mesocaval shunt with artificial vascular graft for the
      treatment of Budd-Chiari syndrome.
AB  - BACKGROUND: Budd-Chiari syndrome (B-CS) is a disease with a poor prognosis, and
      the results of medication are not satisfactory. Surgical treatments are widely
      used to depress portal hypertension and hypertension of the inferior vena cava.
      Splenocaval shunt is usually applied to treat intrahepatic portal hypertension,
      but we used this method to treat patients with B-CS successfully. METHODS: The
      clinical data of 72 B-CS patients (type II), including 26 patients treated with
      splenocaval shunt (splenocaval group) and 46 patients with mesocaval C-shape
      shunt (mesocaval group) were analyzed retrospectively. RESULTS: The platelet
      count of the splenocaval group increased significantly after operation (P<0.05).
      Free portal pressure (FPP) significantly decreased in both groups after operation
      (P<0.05), but no significant difference was seen between the two groups (P>0.05).
      Twenty patients in the splenocaval group and 36 in the mesocaval group were
      followed up for 6 months to 3.5 years, showing the effective rates of 90.0% and
      91.7% respectively in the two groups. The occurrence of hepatic encephalopathy
      was 5.0% and 5.6% respectively in both groups, but there was no recurrent
      hemorrhage. CONCLUSIONS: Splenocaval shunt can effectively control B-CS, decrease
      FPP, prevent upper gastrointestinal hemorrhage, and eradicate hypersplenia. Its
      efficacy is similar to that of mesocaval shunt in treatment of B-CS.

PMID- 15730924
TI  - Effect of hepatitis C virus core protein on modulation of cellular proliferation
      and apoptosis in hilar cholangiocarcinoma.
AB  - BACKGROUND: Hepatitis C virus (HCV) is believed to be an important human pathogen
      causing carcinoma. But the effect of HCV infection on the alteration of cellular
      proliferation and apoptosis and the relationship between the effect and the
      development of hilar cholangiocarcinoma are largely unknown. The aim of this
      study was to assess the effect of HCV core protein on proliferation and apoptosis
      of hilar cholangiocarcinoma. METHODS: HCV core protein (HCV C protein) was
      detected by peroxidase-antiperoxidase assay in surgical specimens from 48
      patients with hilar cholangiocarcinoma. The apoptosis index (AI) and PCNA index
      (PI) in hilar cholangiocarcinoma were detected by in situ end labeling assay and
      streptavidin-biotin assay respectively. RESULTS: The expression of HCV C protein
      was observed in 32 (67.7%) of the 48 specimens of hilar cholangiocarcinoma. The
      mean+/-standard deviation for AI and PI was 3.52%+/-0.64% and 46.24%+/-11.46%
      respectively. The AI of hilar cholangiocarcinoma specimens with HCV C protein
      expression was significantly lower than that of HCV C protein negative specimens
      (P<0.01), whereas the PI of HCV C protein positive specimens was significantly
      higher than that of HCV C protein negative specimens (P<0.01). CONCLUSION: HCV C
      protein may promote the cellular proliferation of hilar cholangiocarcinoma and
      inhibit its cellular apoptosis.

PMID- 15730926
TI  - Hepatitis C virus genotypes, HLA-DRB alleles and their response to interferon
      alpha and ribavirin in patients with chronic hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a worldwide common disease. Some
      predictive factors influencing the response to interferon alpha (IFN-alpha)
      therapy have been identified, but the conclusions differ in various counties and
      areas. The aim of this study was to study the associations between HCV genotypes,
      HLA-DRB alleles and their response to IFN-alpha and ribavirin in Chinese patients
      with chronic hepatitis C in Northeast China. METHODS: HCV genotypes of 113
      patients with HCV were investigated. Gene chips were used to analyze the
      frequency of HLA-DRB in 25 of these patients and their response to IFN-alpha and
      ribavirin. The associations of HCV genotypes, HLA-DRB alleles and their response
      to IFN-alpha and ribavirin were also studied. RESULTS: The response rates
      differed in several types of HCV, with HCV 2b being the highest (57.78%), HCV 1a
      and 2a lower (46.15% and 47.62%) and HCV 1b the lowest (11.76%). The response
      rates to IFN-alpha and ribavirin in patients with DRB1*07 were higher than those
      with DRB1*04. Sex, HCV type and HLA-DRB were all related to the response. Most
      female patients with HCV 2b and HLA-DRB1*07 presented complete response, whereas
      male patients with HCV 1b and HLA-DRB1*04 usually demonstrated no response.
      DRB1*07 allele and HCV 2b were the factors closely related to the response.
      CONCLUSIONS: The response rate of HCV 1b may be the lowest even IFN-alpha and
      ribavirin are combined in treatment. Not only virus but also the host plays an
      important role in anti-virus therapy. Thus, it is necessary to adjust the host's
      immune status to accelerate the clearance of HCV.

PMID- 15730925
TI  - Effects of antisense oligonucleotides of PKC-alpha on proliferation and apoptosis
      of HepG2 in vitro.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies
      in China. The long-term survival rate of patients with HCC after prevention and
      management remains unsatisfactory. In order to provide a novel strategy to cure
      HCC, we investigated the effects of antisense oligonucleotides of PKC-alpha on
      proliferation and apoptosis of human hepatoma cell line HepG2 in vitro. METHODS:
      The human hepatocellular carcinoma cell line HepG2 was cultured and subcultured
      in RPMI1640 medium in vitro. PKC-alpha antisense oligonucleotides(asODN) of
      different concentrations with a random sequence as a control were transfected
      into HepG2 cells by lipofectin(LP). The cell growth index (GI) and the clone
      formation rate of HepG2 were detected by MTT colorimetric assay and soft agar
      assay, respectively. The apoptosis rate of HepG2 treated with PKC-alpha asODN was
      assayed by flow cytometry(FCM). The results were analyzed by SPSS 10.0 software.
      RESULTS: The GI of HepG2 transfected by PKC-alpha asODN with concentrations
      ranging from 0.10 micromol to 1.00 micromol were lower significantly than those
      of control groups (P<0.05). The clone formation rates of HepG2 transfected by PKC
      alpha asODN from 0.05 micromol to 1.00 micromol were lower significantly than
      those of the control groups (P<0.01), and there was a dose-dependent relationship
      among them. The apoptosis rates of HepG2 treated with PKC-alpha asODN from 0.50
      micromol to 1.00 micromol were significantly higher than those of the control
      groups. CONCLUSION: PKC-alpha asODN could inhibit the growth and proliferation of
      HepG2 and induce its apoptosis by blocking the cell signal transduction related
      to PKC-alpha in vitro, and may be potentially used in the prevention and
      management of recurrent and metastatic HCC.

PMID- 15730927
TI  - The U937 cell line induced to express CD14 protein by 1,25-dihydroxyvitamin D3
      and be sensitive to endotoxin stimulation.
AB  - BACKGROUND: CD14 was first described as a differentiation antigen on the surface
      of myeloid lineage cells. It acts as a glycosylphosphatidylinositol (GPI)
      anchored receptor for the complex of lipopolysaccharide (LPS) and plays a key
      role in the activation of LPS-induced monocytes. The purpose of this study was to
      observe the expression of CD14 protein and its gene in the human U937
      promonocytic cell line when these cells were exposed to 1,25-dihydroxyvitamin
      D3(VitD3) and investigate their sensitivity to endotoxin stimulation. METHODS:
      U937 cells were exposed to (0.1 micromol) VitD3 for 24 hours and were induced to
      express the CD14 mRNA gene and CD14 protein, then their responses were observed
      when they were stimulated with different concentrations of LPS for different
      time. RESULTS: The U937 cells induced by VitD3 were found to stably express CD14
      mRNA and CD14 protein. And CD14 protein enhanced the sensitivity of U937/CD14
      cells to lipopolysaccharide (LPS) stimulation. NF-kappaB in U937/CD14 cells can
      be activated with low concentration of LPS (1 ng/ml-10 ng/ml), the TNF-alpha mRNA
      gene was induced, and then TNF-alpha was produced and released into the
      supernatant of culture. CONCLUSION: VitD3 can induce U937 cell to express the
      CD14 gene and CD14 protein and enhance the response of this type of cells to LPS
      stimulation.

PMID- 15730928
TI  - Protein transduction domain of membrane penetrating peptide can efficiently
      deliver DNA and protein into mouse liver for gene therapy.
AB  - BACKGROUND: The development of a harmless and efficient nonviral gene delivery
      system that can facilitate the penetration of nucleic acids through the plasma
      membrane is a key to successful gene therapy. The aim of this study was to test a
      nonviral gene transferring vector's function of delivering DNA into liver cells
      to provide an important clue for gene transfer in liver gene therapy. METHODS:
      The complex of DNA and DNA delivering protein was injected into mice through
      their tail veins. Then the mice were killed and their liver tissue was sectioned.
      The gene transferring results were detected using a confocal laser scanning
      microscope. RESULTS: Fluorescence analysis indicated that both DNA-membrane
      penetrating peptide (MPP) complex and DNA- hepatocyte specific receptor binding
      domain (HSRBD)-MPP complex could go into liver cells. The fluorescence value of
      liver cells in the DNA- HSRBD-MPP group was higher than that in the DNA-MPP
      group. CONCLUSIONS: MPP can successfully deliver DNA and protein into cells, and
      MPP with a HSRBD can specifically deliver DNA into liver cells. These have laid a
      foundation for further study on the nonviral liver cell gene delivering system.

PMID- 15730929
TI  - Establishment and evaluation of the system of extracorporeal liver perfusion in
      pigs.
AB  - BACKGROUND: In recent years, extracorporeal liver perfusion (ECLP) has been
      regarded as a treatment of acute liver failure (ALF); but the system of ECLP has
      many problems. The purpose of this experiment was to detect the factors affecting
      the system of ECLP and to establish a stable and effective system of ECLP.
      METHODS: Livers were harvested from health pigs, according to the different
      styles of perfusion and oxygenation, which were randomly divided into 3 groups.
      The livers in group A (n=4) were subjected to single portal vein perfusion,
      oxygenating perfusion blood; the livers in group B (n=4) to dual (portal vein and
      hepatic artery) vessel perfusion, oxygenating blood, together; and the livers in
      group C (n=4) to dual (portal vein and hepatic artery) vessel perfusion, but
      oxygenating blood, separately. The perfusion time, the data of bile production,
      and hemodynamic parameters of extracorporeal livers in each group were tested.
      The histological examination of liver tissues from each group was performed at
      the end of perfusion. RESULTS: The perfusion time of the liver in group A is
      significantly shorter than in groups B and C (P<0.05). At 1, 3, 6 hours after
      perfusion, the data of bile production and hemodynamic parameters of livers in
      group A were statistically different from those of livers in groups B and C
      (P<0.05). At 1, 3, 6 hours after perfusion, the data of group B were not
      statistically different from those of livers in group C (P>0.05). But at 12 hours
      after perfusion, the data of group B were statistically different from those of
      livers in group C (P<0.01). CONCLUSION: The system of ECLP, which is performed by
      dual (portal vein and hepatic artery) vessel perfusion and oxygenating blood
      separately, is more stable and effective to keep the function of extracorporeal
      liver.

PMID- 15730930
TI  - Endobiliary brush cytology during percutaneous transhepatic cholangiodrainage in
      patients with obstructive jaundice.
AB  - BACKGROUND: Nonsurgical pathologic diagnosis of malignant bile duct stricture
      with a high sensitivity and specificity is desirable for therapeutic scheme.
      Percutaneous transhepatic endobiliary brush cytology in detecting obstructive
      jaundice is evaluated. METHODS: Fifty-eight consecutive patients with obstructive
      jaundice underwent percutaneous transhepatic cholangiodrainage (PTCD). During the
      process, a brush was inserted into the bile duct through the preexisted
      percutaneous transhepatic 8-F sheath, then exfoliated cells were collected from
      the bile duct stenosis and sent for cytologic diagnosis. The suspicious results
      were considered of negative diagnosis. All patients had relevant clinical data
      and follow-up results (15 months to 3 years). Statistical analysis was performed
      with the chi-square test and Fisher's exact test of probabilities, and a P
      value</=0.05 was considered significantly different. RESULTS: Of all patients, 42
      were diagnosed as having malignant stenosis according to brush cytology. Atypical
      hyperplasia was found in 9 patients and was suspicious of cholangiocarcinoma.
      Seven patients were found to have benign strictures. The sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      brush cytology were 75%(42/56), 100%(2/2), 100%(42/42), 12.5%(2/16), and
      75.9%(44/58), respectively. No complications were related to the procedures. In
      all patients with malignant stenosis, the sensitivity of brushing in diagnosis of
      cholangiocarcinoma was greater than that in those with non-cholangiocarcinoma
      (P<0.05). The site of stenosis did not influence the sensitivity and technical
      success (P>0.05). CONCLUSION: The results of this study indicate that cytological
      brushing of biliary stricture during PTCD is a useful method to establish a
      diagnosis of malignant biliary stenosis with a high sensitivity, but the negative
      predictive value is not satisfied.

PMID- 15730931
TI  - Regression of liver fibrosis after biliary drainage in patients with
      choledocholith: a preliminary report.
AB  - BACKGROUND: Choledocholith is prevalent in some Asian countries and may lead to
      liver fibrosis and portal vein hypertension. Biliary drainage is an effective
      treatment for choledocholith. The aim of this study was to assess the impact of
      biliary drainage on liver fibrosis due to choledocholith. METHODS: Eight patients
      with liver fibrosis caused by choledocholith were followed up by biochemical
      tests (aspartate aminotransferase, alanine aminotransferase) and liver biopsy
      before and after biliary drainage, respectively. The severity of the fibrosis was
      scored on a scale from 0 to 3 (0: denoting none; 1: portal and periportal
      fibrosis; 2: the presence of numerous fiber septa; and 3: cirrhosis). The results
      were analyzed statistically. RESULTS: The severity scores of liver fibrosis in
      the 8 patients were 2,1; 2,1; 1,0; 1,1; 2,1; 1,1; 2,1; 1,0 before and after
      biliary drainage, respectively. The results showed that the average severity of
      liver fibrosis decreased significantly after biliary drainage (n=8, t=4.573,
      P=0.003). CONCLUSION: Liver fibrosis due to choledocholith may regress after
      biliary drainage.

PMID- 15730932
TI  - Diagnosis and treatment of biliary atresia: a retrospective study.
AB  - BACKGROUND: Biliary atresia (BA) is the end results of an inflammatory process,
      which affect the intrahepatic and extrahepatic bile ducts, leading to fibrosis
      and obliteration of the biliary tract with the development of biliary cirrhosis.
      Early diagnosis of BA is difficult, and there is no specific therapy for BA at
      present. The purpose of this study was to investigate the diagnosis, treatment
      and postoperative outcome of BA and to explore new diagnostic and therapeutic
      strategies. METHODS: Thirty-one children with biliary atresia from our hospital
      and 201 children with such disease from other hospitals in China were reviewed
      retrospectively in terms of diagnostic modalities, operative age, operative
      methods and long-term survival rates after operation. RESULTS: The operative age
      of the 31 patients varied from 13 to 270 days. It was <60 days in 6 children
      (19%), 61-90 days in 14 (45%), 91-120 days in 8 (26%), and >120 days in 3 (10%).
      No children underwent transplantation for BA. Their 1-6 year survival rate on
      average was 32.3% (10/31). The early operative rate in China was 12.9% (30/232).
      One child received liver transplantation with a long-term survival rate of 31.9%.
      CONCLUSIONS: Early recognition of babies with BA is critical for optimal
      intervention for preventing progressive fibrosis. Clinical presentation, imaging
      and laparoscopy are helpful in enhancing the early diagnostic rate of BA
      patients. The long-term survival rates can be obtained after the improvement of
      operative methods, liver transplantation for children with advanced BA, and
      development of other medical strategies.

PMID- 15730933
TI  - Factors influencing the results of treatment of bile duct injuries during
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The short-term results of repair of laparoscopic bile duct injuries
      have been well discussed, but the long-term results have been rarely reported.
      This study was undertaken to evaluate the factors influencing the outcome of
      repair of bile duct injuries caused by laparoscopic cholecystectomy. METHODS: The
      outcomes of repair of bile duct injuries caused by laparoscopic cholecystectomy
      in 31 patients were reviewed retrospectively, and the effects of injury
      recognition, cholangiography, repair modality and techniques on the long-term
      results were analyzed. RESULTS: Bile duct injuries were repaired successfully in
      19 (95%) of 20 patients with injuries who had been recognized intraoperatively,
      and in 10 (90%) of 11 patients with injuries who had been recognized
      postoperatively. Repair was successful in 29 (93%) of the 31 patients after
      complete cholangiography. Closure of partial division, laceration, or small
      perforation of the bile duct with or without T tube drainage was satisfactory in
      the 23 patients. End to end repair over T tube was successful in 2 transection
      patients, who were detected intraoperatively. Roux-en-Y hepaticojejunostomy was
      used successfully to repair transection, excision or stricture of the bile duct
      in 4 of 5 patients (80%). CONCLUSION: Early detection of bile duct injuries
      caused by laparoscopy, complete evaluation of the biliary duct, and appropriate
      surgical modality and techniques are helpful to improve the results of repair for
      laparoscopic bile duct injuries.

PMID- 15730935
TI  - Effects of dendritic cells transfected with full length wild-type p53 and
      modified by bile duct cancer lysates on immune response.
AB  - BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells
      and are actively used in cancer immunotherapy. Wild-type p53 can be recognized as
      an antigen and can induce specific cytotoxic T lymphocytes (CTLs) in the host
      body. The aim of this study was to investigate the effects of DCs transfected
      with full length wild-type p53 and modified by bile duct lysates on immune
      response. METHODS: The wild-type p53 was transducted to DCs with adenovirus,
      which were modified by bile duct lysates (Lywtp53DC). The concentration of the
      surface molecules (B7-1, B7-2, MHC-I, MHC-II) of all DCs was detected with
      fluorescence activated cell sorter (FACS), and the ability of the DCs to induce
      efficient and specific immunological response in anti-(51)Cr-labeled target cells
      was studied. BALB/c mice infected with the DCs and QBC939 were used. CTL response
      in mice immunized with Lywtp53DC and treatment of tumor-bearing mice with
      Lywtp53DC and CTL response in these mice were studied. RESULTS: The surface
      molecules of Lywtp53DC had a high expression B7-1 (86.70%+/-0.07%), B7-2
      (18.77%+/-0.08%), MHC-I(87.20%+/-0.05%), MHC-II(56.70%+/-0.07%) with FACS. The T
      lymphocytes had a specific CTL lysing ability induced by Lywtp53DC, with a CTL
      lysis rate of 81%. The immune protection of Lywtp53DC group was obvious, and the
      tumor diameter of the Lywtp53DC group was 3.10+/-0.31 mm, 2.73+/-0.23 mm, 3.70+/
      0.07 mm on days 13, 16 and 19, smaller than those of any control groups (P<0.05),
      DC, wtp53DC and LyDC. On the other hand, the growth rate of tumor of the
      Lywtp53DC group was slower than that of any other groups (P<0.05). CONCLUSION:
      Dendritic cells transfected with wild-type p53 and modified by bile duct lysates
      have specific CTL killing capability.

PMID- 15730934
TI  - Overexpression of sterol carrier protein-2 mRNA in patients with cholesterol
      gallstones.
AB  - BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the
      important causes of lithogenic bile. Sterol carrier protein-2(SCP2) participates
      in cholesterol trafficking and metabolism and may play a key role in cholesterol
      gallstone formation. This study was undertaken to investigate the expression of
      liver SCP2 mRNA in patients with cholesterol gallstone and those patients with
      non-cholesterol gallstone. METHODS: The expression of liver SCP2mRNA was studied
      in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol
      gallstone by reverse transcription-polymerase chain reaction (RT-PCR). RESULT:
      The expression of SCP2 mRNA was increased more significantly in patients with
      cholesterol gallstone than in patients with non-cholesterol gallstone.
      CONCLUSION: The SCP2 gene was overexpressed in patients with cholesterol
      gallstone, indicating that SCP2 may be one of the important causes of cholesterol
      gallstone.

PMID- 15730936
TI  - Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and
      associated lung injury.
AB  - BACKGROUND: The exact mechanism by which cyclooxygenase-2 (COX-2) promotes
      inflammation in pancreatitis in obscure. This study was undertaken to investigate
      the role of COX-2 inhibition in an animal model of pancreatitis, a disease
      process characterized by a systemic inflammatory response and ensuing neutrophil
      mediated lung injury. METHODS: Pancreatitis was induced in 24 Sprague-Dawley rats
      by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The
      animals were randomized into 3 groups (8 rats in each group): controls and rats
      with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl
      3 ml/kg)at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and
      lung injuries were assessed histologically. Lung injury was assessed utilizing
      wet:dry ratio and myeloperoxidase activity to indicate pulmonary neutrophil
      infiltration. A Western blot was used to determine COX-2 protein expression in
      pancreatic tissue. RESULTS: The animals treated with COX-2 inhibitors displayed
      significantly less pancreatic and lung injuries than their normal saline
      counterparts. Histological pancreatic and lung injury scores were significantly
      reduced (P<0.05) in the COX-2 treated group. Lung wet:dry ratios were
      significantly improved and pulmonary neutrophil infiltration was attenuated in
      the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2
      protein expression. CONCLUSION: This study shows, for the first time in a rat
      model, that adjuvant COX-2 inhibition significantly attenuates the severity of
      both pancreatitis and its associated systemic inflammatory response and end-organ
      injury.

PMID- 15730937
TI  - Pancreatectomy combined with superior mesenteric-portal vein resection: report of
      32 cases.
AB  - BACKGROUND: Resection of the superior mesenteric-portal vein (SMPV) during
      pancreatoduodenectomy is disputed. Although the morbidity and mortality of
      patients after this operation are acceptable, survival is limited. In this study,
      we evaluated the morbidity, mortality and survival of patients with ductal
      adenocarcinoma of the pancreas who had undergone pancreatectomy with en bloc
      portal vein resection. METHODS: A total of 32 patients with ductal adenocarcinoma
      of the pancreas who had undergone pancreatectomy with SMPV resection between 1999
      and 2003 were retrospectively analyzed. In addition, they were categorized into
      two groups according to the invasion of the wall of the portal vein: group A
      (n=12),extended compression of the wall of the portal vein by surrounding
      carcinoma without true invasion and group B (n=20), true invasion including
      intramural and transmural invasion. RESULTS: The morbidity of the 32 patients was
      31.25%. There was no operative death, and the overall 1-,3-year survival rates
      were 59% and 16%, respectively. The mean survival time of patients with
      microscopically positive margin was only 5.6 months as compared with 20 months in
      patients with microscopically negative margin. No differences in tumor size,
      margin positivity, nodal positivity, and 1-, 3-year survival rates were observed
      between the two groups. CONCLUSIONS: If selected carefully, pancreatectomy
      combined with SMPV resection can be performed safely, without increase in the
      morbidity and mortality. SMPV resection should be performed only when a margin
      negative resection is expected to be achieved. SMPV invasion is not associated
      with histologic parameters suggesting a poor prognosis.

PMID- 15730938
TI  - Diagnosis and treatment of pancreatolithiasis: report of 16 cases.
AB  - BACKGROUND: Pancreatolithiasis is rarely recognized clinically. This study was
      undertaken to assess the value of ultrasonography in the diagnosis of 16 patients
      with pancreatolithiasis and its treatment with pancreatolithotomy plus side-to
      side pancreaticojejunostomy. Extracorporeal shock wave lithotripsy was also used
      in some patients. METHODS: In the 16 patients with pancreatolithiasis treated at
      our hospital from 1977 to June 2002, 3 patients were complicated by pancreatic
      cancer, 2 pancreatic head cyst, and 1 choledochal cyst. Ten patients underwent
      operation, 3 received endoscopic sphincterotomy (EST), and 3 refused operation
      and left the hospital. RESULTS: Epigastric pain was the major symptom of the
      disease. Ultrasonography was the best choice for the diagnosis of the disease in
      addition to CT for determining characteristics and location of pancreatolithiasis
      associated with pancreatic cancer, ERCP for showing pancreatic stone, and EST for
      detecting stone in the pancreatic head. Pancreatolithotomy plus side-to-side
      pancreaticojejunostomy was used for the treatment of pancreatolithiasis.
      CONCLUSIONS: Ultrasonography is the first choice for the diagnosis of
      pancreatolithiasis. Pancreatolithotomy plus side-to-side pancreaticojejunostomy
      is the best choice for the treatment of pancreatolithiasis. CT is of great value
      in determining characteristics and locations of pancreatolithiasis associated
      with pancreatic cancer. For patients with pancreatolithiasis associated with
      pancreatic cancer, surgical treatment should follow the principles of
      individualized therapy.

PMID- 15730939
TI  - Prevention of central cell damage to isolated islets of Langerhans in hamsters by
      low temperature preconditioning.
AB  - BACKGROUND: The efficacy of clinical islet transplantation has been demonstrated
      with autografts, and although islet allografts have established insulin
      independence in a small number of IDDM patients, the treatment is confounded by
      the necessity of central cell damage immunosuppression, the lack of donor tissue,
      and recurring islet immunogenicity. These limitations underscore a need to
      develop therapies to serve the large population of diabetic patients. This study
      was designed to document central cell damage to isolated islets of Langerhans in
      hamsters and its prevention. METHODS: Islets were cultured at 37 degree
      centigrade for 7-14 days after isolation, and then at 26 degree centigrade for
      2,4 and 7 days before additional culture at 37 degree centigrade for an
      additional 7 days. Central cell damage in the isolated islets was monitored by
      video-microscopy and analyzed quantitatively by a computer-assisted image
      analysis system. The analysis included daily measurement of the diameter and the
      area of the isolated islets and the area of the central cell damage that
      developed in those islets over time during culture. Histological examination and
      TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to
      characterize cell damage and to monitor islet function. RESULTS: Microscopic
      analysis showed that during the 7 to 14 days of culture at 37 degree centigrade,
      central cell damage appeared in the larger islets with diameters greater than 200
      microm, which included both necrotic and apoptotic cell death. Low temperature
      (26 degree centigrade) culture prevented central cell damage of isolated islets.
      The 7-day culture procedure at 26 degree centigrade could inhibit most of the
      central cell (excluding diameters greater than 300 microm) damage when the islets
      were rewarmed to 37 degree centigrade. CONCLUSIONS: Our results indicate that
      central cell damage to isolated islets of Langerhans correlates with the size of
      the islets. Low temperature (26 degree centigrade) culture can prevent central
      cell damage to the isolated islets, and is capable to successfully precondition
      these islets for 37 degree centigrade culture. These novel findings may help to
      understand the pathophysiology of early loss of islet tissue after
      transplantation, and may provide a new strategy to improve graft function in the
      clinical setting of islet transplantation.

PMID- 15730940
TI  - Neuroendocrine carcinoma of gallbladder: report of 2 cases.
AB  - BACKGROUND: Neuroendocrine carcinoma of the gallbladder is rare. Its best
      treatment is not known. METHODS: Two patients underwent surgery earlier: one for
      suspected cholecystitis and the other for cholelithiasis. Magnetic resonance
      cholangiopancreatography (MRCP) showed residual lesions in the livers. The two
      patients underwent revision surgery followed by chemotherapy. RESULTS: Both
      patients tolerated the second stage surgery well, which was followed by
      chemotherapy with paclitaxel, ifosphamide and cisplatin for 6 cycles. They were
      treated this way for 8 months and 12 months post treatment, respectively.
      CONCLUSIONS: A proper diagnosis of neuroendocrine carcinoma is made often after
      surgery. As it is a slow growing tumor and not very chemotherapeutically,
      sensitive surgery offers the best local control.

PMID- 15730941
TI  - Diagnosis and management of cystic duct leakage after laparoscopic
      cholecystectomy: report of 3 cases.
AB  - BACKGROUND: Operative complications after laparoscopic cholecystectomy (LC) vary.
      Abdominal pain and other symptoms caused by fluid accumulation in the operative
      area are not uncommon. Cystic duct (CD) leakage is one of the main sources of the
      fluid. This study was to evaluate the procedures used in the diagnosis and
      management of CD leakage after LC. METHOD: The clinical materials of 3 patients
      with CD leakage after LC were studied retrospectively. RESULTS: Three female
      patients underwent LC for chronic cholecystitis associated with stones. Their
      clinical symptoms were worsened of pre-existed cardiac arrhythmia, bile draining
      out from drainage tube, and biliary spillage from umbilical incision,
      respectively. Final diagnosis was made at the 1st, 2nd and 20th post-operative
      day. Two of the 3 patients were treated laparoscopically. Their opened CD stumps
      were closed with an endo-loop, with the abdomen irrigated and drained. The other
      patient was drained with the percutaneous technique, and a biliary stent was
      inserted under endoscopy. All patients recovered well. CONCLUSIONS: The clinical
      manifestations of CD leakage are different. Ascites can be found by B-ultrasound.
      Final diagnosis is dependent on magnetic resonance cholangiography and/or
      endoscopic retrograde cholangiopancreatography. Minimally invasive techniques can
      be applied to this complication safely and effectively. Reoperation for closure
      of the opened CD stump can be fulfilled under laparoscopy. Endoscopic drainage
      must be accompanied with effective abdominal drainage.

PMID- 15730942
TI  - Diagnostic analysis of hepatic angiomyolipoma.
AB  - BACKGROUND: Hepatic angiomyolipoma (HAML) is a rare tumor containing a variable
      amount of fat, vessels and smooth muscle. We report the image findings on
      ultrasonography and computed tomography (CT) of huge HAML. METHOD: The clinical,
      imaging and pathological data of a case of HAML were retrospectively collected
      and analyzed. RESULTS: A huge heterogeneous hyperecho mass with anecho and
      hypoecho areas inside was found in the left hepatic lobe on ultrasonography.
      Color Doppler showed blood flow and arterial spectrum in it. CT scan showed a
      huge heterogeneous solid mass in the left lobe of the liver, with a low density
      and hypervascular area in arterial phase. The serum tumor marks were all
      negative. Ultrasound-guided biopsy was taken twice before resection and both
      showed necrosis tissue and reaction of inflammatory cells. Postoperative
      pathological results showed that the tumor was composed of epithelioid smooth
      muscle cells, thick-walled blood vessels and a few adipose cells with necrosis.
      The immunohistochemistry results showed appearance of typical HAML, with HMB-45
      positive and alpha fetoprotein (AFP) negative. CONCLUSIONS: Preoperative
      diagnosis of HAML relies on combination of CT, MRI and ultrasonography. Our case
      of HAML showed heterogeneous hyperecho image on ultrasonography. Ultrasound
      guided biopsy combined with morphological manifestation and specimen examination
      for HMB-45 may be helpful in the diagnosis of HAML.

PMID- 15730943
TI  - Schema theory: a critical appraisal and reevaluation.
AB  - The authors critically review a number of the constructs and associated
      predictions proposed in schema theory (R. A. Schmidt, 1975). The authors propose
      that new control and learning theories should include a reformulated (a) notion
      of a generalized motor program that is not based on motor program but still
      accounts for the strong tendency for responses to maintain their relative
      characteristics; (b) mechanism or processes whereby an abstract movement
      structure based on proportional principles (e.g., relative timing, relative
      force) is developed through practice; and (c) explanation for parameter learning
      that accounts for the benefits of parameter variability but also considers how
      variability is scheduled. Furthermore, they also propose that new theories of
      motor learning must be able to account for the consistent findings spawned as a
      result of the schema theory proposal and must not be simply discounted because of
      some disfavor with the motor program notion, in general, or schema theory, more
      specifically.

PMID- 15730944
TI  - Developmental changes in the response to obstacles during prehension.
AB  - Adults are proficient at reaching to grasp objects of interest in a cluttered
      workspace. The issue of concern, obstacle avoidance, was studied in 3 groups of
      young children aged 11-12, 9-10, and 7-8 years (n=6 in each) and in 6 adults aged
      18-24 years. Adults slowed their movements and decreased their maximum grip
      aperture when an obstacle was positioned close to a target object (the effect
      declined as the distance between target and obstacle increased). The children
      showed the same pattern, but the magnitude of the effect was quite different. In
      contrast to the adults, the obstacle continued to have a large effect when it was
      some distance from the target (and provided no physical obstruction to movement).

PMID- 15730946
TI  - Alternate response preparation in a visuomotor serial task.
AB  - The preparation of a particular motor pattern is related to the information
      available that enables the actor to predict the correct response to a forthcoming
      stimulus. In many situations, however, prediction is not possible. In such cases,
      the individual can guess the probable parameters of the next stimulus. The
      authors attempted to establish the bias in the motor intention for movement and
      its interaction with a possible memory trace of the stimulus-response mapping
      produced by the preceding stimulus. Two letters were presented bilaterally, and
      participants (N=21) had to discriminate the target letter and respond with the
      compatible hand. The present findings support the existence of a memory trace of
      the previous stimulus-response mapping.

PMID- 15730945
TI  - Gender differences in leg stiffness and stiffness recruitment strategy during two
      legged hopping.
AB  - The authors compared leg stiffness (K(VERT)), muscle activation, and joint
      movement patterns between 11 men and 10 women during hopping. Physically active
      and healthy men and women performed continuous 2-legged hopping at their
      preferred rate and at 3.0 Hz. Compared with men, women demonstrated decreased
      K(VERT); however, after the authors normalized for body mass, gender differences
      in K(VERT) were eliminated. In comparison with men, women also demonstrated
      increased quadriceps and soleus activity, as well as greater quadriceps-to
      hamstrings coactivation ratios. There were no significant gender differences for
      joint movement patterns (p>.05). The relationship between the observed gender
      differences in muscle recruitment and the increased risk of anterior cruciate
      ligament injury in women requires further study.

PMID- 15730947
TI  - Muscle activation is different when the same muscle acts as an agonist or an
      antagonist during voluntary movement.
AB  - During movement, the intrinsic muscle force-velocity property decreases the net
      force for the shortening muscle (agonist) and increases it for the lengthening
      muscle (antagonist). The authors present a quantitative analysis of the effect of
      that muscle property on activation and force output of the same muscle acting as
      agonist and antagonist in fast and medium speed goal-oriented movements. They
      compared biceps activation and force output when that muscle was the agonist in a
      series of elbow flexions and when it was the antagonist in a series of elbow
      extensions. They performed the same analysis for the lateral, long, and medial
      heads of the triceps muscle. Muscle EMG was about 2 times larger and the angular
      impulse developed by the modeled contractile torque was up to 3 times larger when
      the muscle or muscles acted as the agonist than when the same muscle or muscles
      acted as the antagonist in movements with similar kinematics. The large effect of
      the muscle force-velocity property strongly suggests that the neural controller
      must account for intrinsic muscle properties to generate movements with a
      commonly observed bell-shaped velocity profile.

PMID- 15730948
TI  - Dissociation of bimanual responses with the Simon effect: on the nonunitization
      of bimanual responses.
AB  - The authors examined whether responses of the 2 hands were completely unitized
      when participants (N=36) produced bimanual responses to lateralized targets in a
      Simon-type paradigm. Their primary aim was to investigate whether lateralized
      stimuli differentially influence the response dynamics of the 2 hands. Simon
      effects were obtained in reaction time and force components of the bimanual
      response by the hand on the same side as the lateralized stimulus were more
      forceful than were those of the other hand. Also, Simon effects were larger when
      the lateralized target appeared alone than when it was accompanied by a
      distractor on the other side of the display. Finally, responses of the 2 hands
      were correlated most strongly when stimulus displays were symmetrical. The
      authors conclude that bimanual responses are strongly coupled, but not perfectly
      so.

PMID- 15730949
TI  - The use of anticipatory visual cues by highly skilled tennis players.
AB  - The authors examined 13 skilled and 12 novice tennis performers' ability to use
      visual information of an opponent's movement pattern to anticipate and respond.
      In Experiment 1, skilled and novice players anticipated the type of stroke and
      the direction in which the ball was hit in a highly coupled perception-action
      environment. Both groups of players correctly anticipated at greater than chance
      levels. Skilled players were significantly more accurate than novices with live
      and video displays but not with point-light displays. In Experiment 2, the
      reaction latencies of 10 expert performers were significantly faster when they
      returned balls hit by a live opponent than when they returned balls projected
      from a cloaked ball machine. The findings indicate that experts are able to use
      movement-pattern information to determine shot selection and to use that
      information to significantly reduce their response delay times. The findings are
      discussed in terms of perception-action coupling in time-stress activities.

PMID- 15730950
TI  - [Recognition and study of susceptible gene to ankylosing spondylitis].
AB  - To study the potential correlations between variances of TNFalpha gene and onset
      of ankylosing spondylitis in Chinese population, We scanned and analyzed the
      promoters of TNFalpha genes in 75 AS patients from south of China and found -850
      T mutation allele frequency rather high (39.3%).By case-control study, the
      distribution of TT genotype is significantly higher in AS patients than that in
      normal subjects (10.7% VS 2.1%,P=0.003); Mutation T allele has a remarkable
      difference between AS group and normal control (72.2% vs 21.4%,P=2.729 x 10(-9)).
      The difference in distribution of TX genotype and non -TX genotype is also
      significant statistically between different genders(male: P=3.42 x 10(-9);female:
      P=0.001). The result suggests that this variation has a strong association with
      AS in males and females. No similar reports about the association between AS and
      the T mutation allele have been acquired. Therefore, our hypothesis can be
      supported by our results on the whole and the -850 C-->T mutation allele in the
      region on promoter of TNFalpha gene is likely one of susceptible genes to AS.

PMID- 15730951
TI  - [Molecular cloning and characterization of hMGRAP, a human secreted protein with
      multiple glutamine repeat].
AB  - To search for human novel secreted proteins and study their biological functions,
      using bioinformatical tools and experimental approaches, a novel secreted
      protein, human hMGRAP (Human Multiple Glutamine Repeat Acidic Protein) was
      obtained. hMGRAP consists of six coding exons spanning 1547bp of genomic DNA on
      the human chromosome 7q22.1, which encodes a protein with 248 amino acids. hMGRAP
      is rich of glutamic acid repeated sequence and the PI is 4.6. The coding sequence
      of hMGRAP was cloned by PCR method from the cDNA pool composed of nine human
      tissues. Western blot showed that hMGRAP protein was massively secreted out from
      the transiently transfected Cos-7 cells. RT-PCR result indicated hMGRAP mRNA was
      abundantly expressed in testis. In summary, a novel human gene encoding a
      secreted protein hMGRAP has been screened and cloned, and its biological function
      may specifically relate to its repeated glutamic acid sequence.

PMID- 15730952
TI  - [Mutations in the D-loop region of mitochondrial DNA and the ROS level in the
      tissue of hepatocellular carcinoma].
AB  - To explore the relationship between ROS level and mutations in D-Loop region of
      mtDNA, mutations in the D-Loop region of mtDNA and the ROS level in primary
      hepatocarcinoma tissues were studied. We amplified the D-Loop region of mtDNA of
      20 hepatocarcinomas and their adjacent tissue by PCR and then sequencing. ROS in
      tissue was measured by flow cytometry. mtDNA mutations were detected in 40% (8 of
      20) tumor samples. 53 point mutations were detected in eight tumour samples,
      including 2 insertions, 11 deletions and 40 point mutations. 75% point mutations
      were T-C and C-T transition. They were four microsatellites among the mutations.
      Mutations in the adjacent tissues were always companied with mutations in tumour
      tissues. The mutation frequency in tumour tissues was higher than that in
      adjacent tissue. There was a larger unidentified deletion. The ROS level in
      hepatocarcinoma tissue was much higher than control (P<0.01). Meanwhile, we found
      the ROS level in hepatocarcinoma tissues with mutated mtDNA D-Loop was higher
      than that hepatocarcinoma tissue normal mtDNA D-Loop, and the ROS level in
      hepatocarcinoma adjacent tissue with mutated mtDNA D-Loop was higher than that in
      hepatocarcinoma adjacent tissue with normal mtDNA D-Loop. It was concluded that
      the D-Loop region of mitochondrial DNA was a highly polymorphoric and mutable
      region and mutation rate was relatively high in patients with hepaticellular
      carcinoma, and the abnormal ROS level might be the point mutation in the
      mitochondrial DNA and hepatocarcinogenesis related to ROS.

PMID- 15730953
TI  - [Genetic polymorphism of D1S1612 and D18S535 in Chinese Han population of
      Beijing].
AB  - To investigate the genetic polymorphism of D1S1612 and D18S535 in Han population
      of Beijing. Amp-FLP method was used. 9 alleles, 25 genotypes were observed for
      D1S1612 locus; and 9 alleles and 27 genotypes for D18S535 locus. All allele
      frequencies, heterozygosity (H), discrimination power (Dp), exclusion of
      paternity probability (PE) and polymorphism information content (PIC) were
      calculated. The allele distributions of the two loci were conformed to Hardy
      Weinberg equilibrium (P>0.01). According to the results obtained in this study,
      it is suggested that both D1S1612 and D18S535 are useful genetic markers for
      individual identification and paternity testing in forensic science practice as
      well for genetic study.

PMID- 15730954
TI  - [Genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han
      population].
AB  - In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in
      southern Chinese Han population, the polymorphisms of the gene's promoter and its
      five exons among peripheral blood lymphocytes of 172 Chinese Han people were
      analyzed with polymerase chain reaction-single strand conformation polymorphism
      (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1
      gene were conserved. A T to C polymorphism was detected at the 73th base in exon
      2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The
      allelic frequencies of T and C were 96.51% and 3.49%, respectively. A T to C
      polymorphism was detected at codon 45 in exon 3, which was first reported. The
      genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The
      allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A
      polymorphism was detected at codon 83 in exon 4. The genotype frequencies of GG
      and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A
      were 94.77% and 5.23%, respectively. A C to T polymorphism was detected at codon
      119 in exon 5. The genotype frequencies of CC and CT were 95.93% and 4.07%,
      respectively. The allelic frequencies of C and T were 97.97% and 2.03%,
      respectively.

PMID- 15730955
TI  - [The sequence polymorphism of Y-chromosome DNA and mtDNA of Dong Ethnic of
      Congjiang, Guizhou].
AB  - To study the patrilineal and matrilineal genetic structure and the origin of Dong
      Ethnic of Congjiang Guizhou. Study the distribution of Y-chromosome haplotypes
      which consisted of 10 SNPs of Y-DNA and mtDNA haplogroups consisted of 11 SNPs by
      using PCR-RFLP method. The result is three haplotypes H6,H11,H14 were detected,
      the frequency of H11 is 92.5%. Six haplogroups were identified by mtDNA analysis,
      75% of the people can be identified. The patrilineal genetic structure of Dong of
      Guizhou is simple, Principle component indicated that the structure is closer to
      Zhuang-Dong branch of Sino-Tibetan language family. The matrilineal genetic
      structure of Dong of Guizhou is complicated.

PMID- 15730956
TI  - [Association study of apolipoprotein e gene polymorphism and cerebral infarction
      in type 2 diabetic patients].
AB  - In order to explore the association of apolipoprotein E (ApoE) gene polymorphism
      with cerebral infarction in type 2 diabetic patients of Han nationality in
      Northeast China , the genotypes of ApoE gene were analyzed by polymerase chain
      reaction -restriction fragment length polymorphism (PCR-RFLP) in the 208 cases,
      including 69 cases in control (CON) group and 67 in type 2 diabetes mellitus
      (T2DM) group as well as 72 in type 2 diabetes mellitus with cerebral infarction
      (T2DMCI) group. Plasma lipid content in T2DMCI was also detected for 70 cases.
      The distribution of genotypes in ApoE
      gene,epsilon(2)epsilon(3),epsilon(3)epsilon(3) as well as epsilon(3)epsilon(4)
      was no significant difference in three groups (epsilon(2)epsilon(3) :
      13.2%,epsilon(3)epsilon(3) : 67.6%,epsilon(3)epsilon(4) : 16.2%in CON
      group;epsilon(2)epsilon(3) : 19.4%,epsilon(3)epsilon(3): :
      70.1%epsilon(3)epsilon(4) : 9%in T2DM group;epsilon(2)epsilon(3) :
      15.2%,epsilon(3)epsilon(3) : 75%,epsilon(3)epsilon(4) : 4.2%in T2DMCI group). The
      allele frequencies of epsilon(2),epsilon(3) and epsilon(4) were not significantly
      different in the three groups, either(epsilon(2) : 9.6%,epsilon(3) :
      82.4%,epsilon(4) : 8.1%in CON group; epsilon(2) :10.5%,epsilon(3)
      :84.3%,epsilon(4) : 5.2%in T2DM group; epsilon(2) :11.8%,epsilon(3)
      :84.7%,epsilon(4) : 3.5%in T2DMCI group). The levels of total cholesterol (TC),
      tryglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density
      lipoprotein-cholesterol (LDL-C) were not significantly different among the
      different genotypes in T2DMCI group. The study confirmed that the polymorphisms
      of ApoE gene are neither associated with the T2DMCI, nor with the levels of
      plasma lipid in T2DMCI.

PMID- 15730958
TI  - [Heteroplasmy: a common phenomenon of mitochondrial genome mutations in human
      tumor tissues].
AB  - To explore the status of heteroplasmy and homoplasmy of Mitochondrial DNA somatic
      mutations in different tumors. DNA from 149 tumors and corresponding normal
      tissues were extracted and entire mitochondrial genome was amplified using 32
      pairs of overlapping primers. The somatic mutations were screened by temporal
      temperature gradient gel electrophoresis and their heteroplasmic statute were
      identified by sequencing. The results showed that the incidence rate of
      heteroplasmy of mitochondrial DNA somatic mutations varies in different tumors.
      There is a high rate of heteroplasmic mutation in oral cancer (65%) and
      esophageal cancer (64%), followed by breast cancer (45%). The frequency of four
      transfer types is Hm (homoplasmy)-->Hm (heteroplasmy) > Hm-->Ht > Ht-->Hm > Ht-
      >Ht. The main transfer forms of transition and transversion mutations are Hm-->Hm
      and Hm-->Ht respectively. Heteroplasmy is a common phenomenon in mitochondrial
      DNA somatic mutations of human tumors.

PMID- 15730957
TI  - [Methylation and aberrant expression of the p16 gene in cervical carcinoma].
AB  - To detect hypermethylation and aberrant expression of the p16 gene in cervical
      carcinoma (CC), methylation-specific PCR (MSP) was used to determine the
      methylation status of 5'CpG islands of the p16 gene, loss or decrease of p16
      expression was analyzed by immunohistochemistry (IHC), and homozygous deletion of
      exon 1 (E(1)) and/or exon 2 (E(2)) was determined by PCR. in 60 cases of CC at
      different pathological grades and clinical stages. The results showed absence of
      methylation and presence of normal expression of the p16 gene in the control and
      adjacent tissues of CC. Hypermethylation, loss or decrease of expression and
      deletion of the p16 gene were detected in 21.67%(13/60), 51.67%(31/60) and
      15.00%(9/60) of the tumor tissues, respectively. The rate of p16 expression
      markedly reduced with the increase of clinical stages. Our data suggested that
      inactivation of the p16 gene was a frequent event and positively correlated with
      pathological grades in CC, and that methylation of the p16 gene was an important
      event in carcinogenesis of CC.

PMID- 15730959
TI  - [DMDUse of fetal specific antibody-HbF to detect fetal erythroblasts for non
      invasive prenatal diagnosis of DMD].
AB  - Maternal blood was obtained at 8-26 weeks of gestation. After discontinuous
      density gradient centrifugation with Percoll, HbF antibody was used to identify
      fetal NRBC. The precise differentiation between fetal and maternal NRBC is based
      on the constitutional difference between fetal and adult hemoglobin (Hb). Fetal
      cells appear yellow cytoplasmic staining,while adult cells colorless. NRBCs were
      collected by micromanipulation and whole genome amplification was performed. DMD
      was prenatally diagnosed by using the combination of sex determination,multiplex
      PCR and linkage analysis of several STR sites of dystrophin. NRBCs stained with
      HbF were found in all of 20 maternal blood samples with gestations, and 7 fetuses
      with risk of DMD were diagnosed. We concluded that HbF antibody could identify
      fetal NRBC efficaciously, and this is a kind of more prospective application
      method.

PMID- 15730960
TI  - [Mutations in exon 7 of the phenylalanine hydroxylase (PAH) gene in chinese
      patients with phenylketonuria].
AB  - To study mutation in exon 7 of the gene for the phenylalanine hydroxylase(PAH),
      the mutations in exon 7 and flanking sequence of PAH gene were detected by means
      of SSCP analysis and DNA sequencing, in 147 unrelated Chinese children with
      phynelketonuria and their parents. Thirteen different mutations, including 11
      missense, 1 deletion and 1 splice mutation, were revealed in 90/294 mutant
      alleles (30.61%). The prevalent mutations were R243Q (22.8%) and Ivs7nt2t->a
      (2.38%). Seven novel mutations were identified: G239D, R241fsdelG, G247S, E280G,
      L255S, R261Q, P281L. These new mutations have not been described in Chinese PKU
      population and the first 4 mutants have not been reported and thus been submitted
      to www.pahdb,mcgill.ca. The missense was the most common type. The deletion and
      frameshift mutations were detected for the first time in Chinese PKU population.
      This study showed the mutation characteristics and their distribution in exon 7
      of PAH gene and proved that the exon 7 was the hot region of PAH gene mutation in
      Chinese PKU population .

PMID- 15730961
TI  - [Quantitative analysis of human globin gene expression in beta-thalassemia using
      real-time RT-PCR].
AB  - Whole blood samples were collected from 100 normal healthy adults, from umbilical
      cord of 33 newborn infants, 111 individuals with beta-thalassemia minor
      (beta(T)/beta(A),alphaalpha/alphaalpha) and 39 with beta-thalassemia major
      (beta(T)/beta(T),alphaalpha/alphaalpha). Prior to quantitative analysis of globin
      gene expression, DNA was extracted from all blood samples and used for beta
      thalassemia genotype analysis. Different types of beta globin gene mutations were
      analyzed using reverse dot blotting (RDB) method. Total RNA were extracted and
      subjected to real-time RT-PCR for quantitative measurement of alpha, beta and
      gamma globin mRNA using three sets of primers and fluorescent-labeled probes,
      designed according to the sequences of alpha, beta and gamma human globin gene.
      Real-time RT-PCR was performed in ABI 7700 system. Following the real-time RT
      PCR, the mean values of alpha, beta and gamma globin mRNA were calculated and the
      ratios of alpha/beta, alpha/(beta + gamma ) and gamma /(beta + gamma ) were
      determined to characterize the relative expression levels of different globin
      genes among normal adult, infant, beta-thalassemia minor and beta-thalassemia
      major patients. The resultant data were analyzed using SPSS 10.0 software to
      determine statistical significance of human globin gene expression among normal
      controls and beta-thalassemia patients. Due to vast variations of the mean globin
      gene mRNA levels among different groups, log conversion of alpha/beta + 1,
      alpha/(beta + gamma ) + 1 and gamma /(beta + gamma ) +1 was used for statistical
      analyses and intergroup comparison. The alpha/beta globin gene mRNA ratios were
      determined to be 4.62+/-1.20, 7.81+/-2.89, 13.51+/-5.12, and 188.24+/-374.04 for
      normal healthy adult (beta(A)/beta(A),alphaalpha/alphaalpha), infant
      (beta(A)/beta(A),alphaalpha/alphaalpha), beta- thalassemia minor
      (beta(T)/beta(A),alphaalpha/alphaalpha) and beta-thalassemia
      major(beta(T)/beta(T),alphaalpha/alphaalpha) respectively. The alpha/(beta+ gamma
      ) ratios were 4.43+/-1.17, 0.56+/-0.49, 9.62+/-4.37, and 2.14+/-1.58 for normal
      healthy adult (beta(A)/beta(A),alphaalpha/alphaalpha), infant
      (beta(A)/beta(A),alphaalpha/alphaalpha), beta- thalassemia minor
      (beta(T)/beta(A),alphaalpha/alphaalpha) and beta- thalassemia
      major(beta(T)/beta(T),alphaalpha/alphaalpha) respectively. The gamma /(beta+
      gamma ) ratios were 0.04+/-0.03, 0.92+/-0.06, 0.28+/-0.18, and 0.95+/-0.04 for
      normal healthy adult (beta(A)/beta(A),alphaalpha/alphaalpha), infant
      (beta(A)/beta(A),alphaalpha/alphaalpha), beta- thalassemia minor
      (beta(T)/beta(A),alphaalpha/alphaalpha) and beta- thalassemia major
      (beta(T)/beta(T),alphaalpha/alphaalpha) respectively. Following statistical
      analyses, the alpha/beta and alpha/(beta+ gamma ) globin gene mRNA ratios were
      significantly different among four different groups (normal adult, normal infant,
      beta- thalassemia minor and beta- thalassemia major). The gamma /(beta + gamma )
      globin gene mRNA ratio was significantly different among all groups except for
      between infant and beta- thalassemia major patients. Human beta globin gene mRNA
      levels decrease progressively and dramatically from normal adults to beta
      thalassemia patients with beta-thalassemia major having the lowest levels. On the
      other hand, the gamma globin gene mRNA levels increase progressively from normal
      adult to beta-thalassemia patients with beta-thalassemia major having the highest
      levels. Infants have relatively lower levels of beta but higher levels of gamma
      globin gene mRNA as compared to those in normal adults. Thus, the relative
      expression levels of alpha, beta or gamma globin genes varied but inter-related
      among different ages of normal individuals and different beta-thalassemia
      genotypes.

PMID- 15730962
TI  - [Studies on carcass and meat quality performance of crossbred pigs with graded
      proportions of Laiwu Black genes].
AB  - Sixty pigs, including pure Laiwu Black (LL), pure Large Yorkshire (YY), 1/2 Laiwu
      (Ymale x Lfemale), 3/4 Laiwu (Lmale x YLfemale) and 1/4 Laiwu (Ymale x YLfemale),
      were housed in groups with the same diet until 90 kg for slaughter. The
      objectives were to investigate the effects of graded proportions of Laiwu Black
      genes on carcass and meat quality performance. Results indicated that different
      consanguinity had significant effect on carcass weight, carcass length (CL), ham
      percentage (HP) and backfat thickness (BT) (P<0.05), and had highly significant
      effect on eye muscle area (EMA) and lean percentage (LP) (P<0.01). Furthermore,
      CL, HP, EMA and LP tended to increased gradually, but BT tended to decreased
      gradually as Laiwu Black genes decreased. For meat quality properties, different
      consanguinity had significant effect on meat color, marbling score, dry matter
      and crude protein content of muscles (P<0.05), and had highly significant effect
      on water loss, drip loss and intramuscular fat content of muscles (P<0.01).
      Compared with the muscle of Large Yorkshire, that of Laiwu Black and its
      crossbred pigs were bright red in meat color, high in water holding capacity and
      abundant in intramuscular fat. Results implied that to give attention to both
      quantity and quality, Laiwu Black surely has usable precious value in superior
      pig production. Commercial crossbred pigs should have about 1/4 of Laiwu Black
      genes.

PMID- 15730963
TI  - [Genetic analysis of 32 microsatellite loci in 13 families of Wuzhishan pig by
      multiplex PCR and gene scanning technique].
AB  - Wuzhishan pig is one of the rare and endangered breeds in china. They have the
      following characteristics such as :light body weight and small size, early
      sexually maturity, high meat quality and genetic identification with 6
      approximately 8 pares litter size,body weight of born 0.3 approximately 0.4 kg,
      15 approximately 16 kg at 6 month old, 35 kg at 2 years old, and so on. They may
      be used for laboratory utilization, comparative studies on human medical model,
      embryonic engineering, nutrition metabolism, sensitivity test on virus and
      bacteria, skin brut and tranfer, removing lipid, teeth and mouth cavity diseases,
      studies on cardiovascular model and evaluation of new medicine products. The
      polymorphisms of 32 microsatellites in 13 families of Wuzhishan pig in Hainan
      were Analysed. Number of alleles in each family was counted, mean heterozygosity
      and polymorphism Information content(PIC) were calculated. The results showed
      that number of alleles was 13.66, mean heterozygosity was 0.559 while
      polymorphism information content was 0.731. This revealed that genetic diversity
      is abundant in Wuzhishan pig in Hainan. These results have instructional
      significance for preserving breeds, selection and breeding, development and
      utilization of Wuzhishan pig in Hainan.

PMID- 15730964
TI  - [Genetic structure and phylogeny status of Chaidamu goat population].
AB  - Genetic structure and character of Chaidamu goats were studied through simple
      random sampling. Genetic structure was analysed from five aspects, and phylogeny
      status was also investigated. The results indicated that: (1) the average
      phenotypic heterogeneity degree of coat color and morphological character were
      0.3419 and 0.5207, respectively; (2) polymorphous blood albumen existed in 6 loci
      and the average loci heterozygosity was 0.2584; and (3) polymorphism existed in
      marked genes by DND-RAPD with diversity of 0.4085 approximately 0.5318. Phylogeny
      status was investigated through clustering by Ward's method on Chaidamu Goats and
      other domestic goats. All these indicated that Chaidamu Goats was a domestic goat
      with less intensively selected breed.

PMID- 15730965
TI  - [Detection of major gene on litter size in sheep].
AB  - The current study was designed to detect SNPs within BMP15 and BMPR-IB gene and
      investigate the effect of the genes on sheep litter size. Four sheep lines, HU
      Yang, Chinese Merino monotocous, Chinese Merino multiparous for wool production
      and Chinese Merino multiparous for mutton production, were used in this study.
      Litter sizes were recorded for each ewe in the four lines. Primers for BMP15 and
      BMPR-IB gene were designed from database sheep sequence and polymorphisms were
      detected by PCR-RFLP method. The results showed that there was no polymorphism
      with BMP15 gene among the four lines, and there was an A / G SNP with BMPR-IB
      gene at base 746 among the four lines. Three types of genotype (BB, B+ and ++),
      based on A / G locus, were found within each line. The frequencies of genotypes
      were significantly different among the lines (P<0.001), with BB genotype
      primarily existing in HU-Yang, ++ genotype in Chinese Merino monotocous line, and
      B+ genotype in Chinnese Merino multiparous lines. The A / G mutation influence
      significantly the sheep litter sizes, and the BB and B+ ewes had significant
      higher litter sizes than ++ ewes. The results of present study showed
      simultaneously that the genotype of BMPR-IB was a perfect predictor of the sheep
      litter sizes. These results intensively indicated that BMPR-IB is a major gene to
      affect litter size in sheep, and could be used as the molecular genetic marker to
      select litter size in sheep.

PMID- 15730966
TI  - [Microsatellite markers for paternity testing of Liangshan semi-fine wool sheep].
AB  - The usefulness of multiplex polymerase chain reaction was evaluated and
      fluorescent detection with 20 microsatellites was used for paternity testing of
      Liangshan semi-fine wool sheep. The results in Cervus 2.0 indicated that the
      combined exclusion probability was 0.998666 when parents were both unknown. If
      father was known, combined exclusion probability was 0.999994, with confidence
      level of 95%. Finally, the biological parents of 215 individuals in offspring
      were found from 8 candidate fathers and 147 candidate mothers, and a mixed
      pedigree was constructed. It is useful for linkage analysis of sheep chromosomes
      and QTL location, also for the study of population structure, history, and
      diversity.

PMID- 15730967
TI  - [Sequence comparing of mtDNA D-Loop varied region in Chinese Mongolian horse and
      External Thoroughbred horse].
AB  - Mitochondrial DNA D-Loop varied region 400 bp sequence variations in 4 Chinese
      Mongolian horses and 4 External Thoroughbred horses were analyzed in this
      experiment. The results showed that the average nucleotide mutational rate of
      mtDNA D-Loop varied region in 4 Chinese Mongolian horses was 3.69%, while
      External Thoroughbred horses were 4.00%. Three types of mutations including
      transition, transversion and deletion were all found in the investigated mtDNA D
      Loop regions, of which transition was the most frequent. Nucleotide mutational
      loci were abundant, length mutations were found and great differences were all
      observed among the 8 horses. It showed there existed much polymorphism in the
      mitochondrial DNA D-Loop varied region of Chinese Mongolian horses and External
      Thoroughbred horses.

PMID- 15730968
TI  - [Phylogenetic relationship between tufted deer(Elaphodus cephalophus) and
      Muntiacus deer is revealed by the exon and intron of K+ channel gene].
AB  - In this study, partial fragments of potassium ion channel gene were amplified
      using the genomic DNA of muntjak, reevesi, crinifrons, and Elaphodus cephalophus.
      The PCR products were ligated to the plasmid of pMD18-T Vector by the method of
      direct T-A cloning. The positive clones were identified by colony PCR. The
      sequences of the recombinant clones were determined using M13-47/RV-M universal
      primers and aligned by the software CLUSTALW. The nucleotide divergences of exon
      were 0.90%-1.44% among three species of Muntiacus, 0.90%-1.26% between E.
      cephalophus and each of Muntiacus deer. In the nucleotide of intron there is 0%
      1.22% difference among these muntjac deers, and the divergene reached about 1.83%
      between E. cephalophus and the three species of Muntiacus. Using the software of
      MEGA to analyse molecular phylogeny, Phylogenetic trees were constructed with
      neighbor-joining method and maximum parsimony method. The result showed
      Muntiacus, crinifrons is most closely related to muntjak, with reevesi as their
      sister species. E. cephalophus is in the other genus.

PMID- 15730969
TI  - [Gene studies and nobel prize].
AB  - Gene is a DNA sequence which can be expressed and produces gene products (protein
      or RNA). By 2003, there are 51 Nobel Prize owners related to gene studies. Among
      them, 44 persons are in physiology or medicine (account for 24.72% of total 178),
      7 persons are in chemistry (account for 5.69% of total 123). The paper reviews
      them in following 6 aspects: Drosophlie melanogaster is a good material for gene
      study; the double helix model of DNA structure provides a hard foundation in gene
      study; the studies on gene regulation illuminate many functions of gene; genetic
      central dogma researches created 11 Noble Prize laureates; gene engineering
      technologies make possible to modify and use genes; and the thorough studies of
      gene characteristic made us easier to understand many life phenomena.

PMID- 15730970
TI  - [Detection for single nucleotide polymorphisms].
AB  - As the third generation of genetic markers SNPs (single nucleotide polymorphisms)
      has been used extensively in gene mapping,disease-correlativity analysis
      ,population genetics and drug research. Here methods for detection are reviewed.
      Most SNP genotyping are a combination of method for interrogating SNPs and
      analysis technique.It described both parts and give a outlook for detection.

PMID- 15730971
TI  - [Progress in detection methods of single nucleotide polymorphisms].
AB  - Single nucleotide polymorphism (SNP) is the third generation genetic marker. SNP
      detection now is becoming increasingly important means in molecular diagnostics,
      clinical assay and novel drug development. It plays an essential role in drug
      resistance and anaphylactic reaction and has the importance in theoretical
      studies of gene location, hereditary diseases and human origin. With the
      accomplishment of human genome sequencing, the genotyping and discovering of SNP
      are becoming hot subjects in genetics and biomedicine researches. The methods for
      SNP detection were renewed rapidly and developed fast in past few years. In this
      review, several newly established detection methods including gene chip,
      molecular probe, fluorescence polarization and resonance, mass spectrometry, and
      bacterial magnetic particle are discussed. It could be expected that an accurate
      and sensitive, simple and easy-to-handle SNP technology with low cost and high
      throughput will be available on the basis of research breakthroughs of
      biochemistry, engineering and analytic software.

PMID- 15730972
TI  - [Segregation analysis of genetic system of quantitative traits in plants].
AB  - Based on the traditional polygene inheritance model of quantitative traits, the
      mixed major gene and polygene inheritance model was raised and considered as the
      general model, while pure major gene or pure polygene inheritance model being
      only the specific case of the general model. From the proposed theory, the
      segregation analysis procedure was established for studying the genetic system of
      quantitative traits of plants. At present this procedure can be used to evaluate
      the genetic effects of individual major genes (up to 2-3 major genes) and the
      collective genetic effects of polygenes as well as their heritability values. The
      present paper introduces the process of the establishment of the procedure, main
      achievements and application results. An example was given to illustrate the
      steps, methods and effectiveness of the procedure.

PMID- 15730973
TI  - [Progress in porky genes and transcriptome and discussion of relative issues].
AB  - To date, research on molecular base of porky molecular development was mainly
      involved in muscle growth and meat quality. Some functional genes including Hal
      gene and RN gene and some QTLs controlling or associated with porky growth and
      quality were detected through candidate gene approach and genome-wide scanning.
      Genic transcriptome pertinent to porcine muscle and adipose also came into study.
      At the same time, these researches have befallen some shortcomings to some
      extent. Research from molecular quantitative genetics showed shortcomings that
      single gene was devilishly emphasized and co-expression pattern of multi-genes
      was ignored. Research applying transcriptome analysis tool also met two of
      limitations, one was the singleness of type of molecular experimental techniques,
      and another was that genes of muscle and adipose were artificially divided into
      unattached two parts. Thus, porky genes were explored by parallel genetics based
      on systemic views and techniques to specially reveal the interactional mechanism
      of porky genes respectively controlling muscle and adipose, which would be
      important issues of genes and genome researches on porky development in the near
      future.

PMID- 15730974
TI  - [Gene duplications specific to the amphioxus lineage].
AB  - The union of the two complementary disciplines, developmental biology and
      evolutionary biology resulted in a new division of evolutionary developmental
      biology, namely "Evo-Devo". Recently, the research on this field has been
      fruitful in understanding the origin and development of vertebrates. The
      cephalochordate amphioxus, which remains in relatively invariant morphology since
      the divergence from the vertebrate lineage, is the closest living relative to
      vertebrates. The vertebrate-like simple body plan and preduplicative genome
      provide amphioxus genes the privilege to serve as key landmark to understand
      morphological evolution. However, the amphioxus genome has not escaped evolution.
      In this paper several examples of independent gene (Hox; Evx; HNF-3 and
      Calmodulin-like) duplications in the cephalochordate lineage were summarized.
      These particularities and oddities remind the fact that amphioxus is not an
      immediate 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- 15730975
TI  - [Transformer genes and sex determination of C. elegans and D.melanogaster].
AB  - Sex determination of Drosophila melanogaster and Caeborhabditis elegans has been
      known in detail. Great progress, is achieved in recent years, is the research of
      transformer genes, which are those of most important genes in sex determination
      in both species. In this paper, molecular character, genetic function and the
      relative genes of transformer genes are particularly described. On the basis,a
      primary comparison and analysis between the molecular mechanism of sex
      determination in C.elegans and D. melanogaster are presented.

PMID- 15730976
TI  - [Epigenetics promotes a new round of the genetic development].
AB  - Scientific development is pregnant with a breakthrough, epigenetic studies are
      pushing the genetics forward. Epigenetics is the study of heritable changes in
      gene expression that occurs without a change in DNA sequence. Epigenetics not
      only has practical significance for medicine and agriculture, but also provides
      new views on understanding heredity and evolution. Human genome contains
      information in two forms: the genetic information provides the blueprint for the
      manufacture of all the proteins necessary to create a living thing while the
      epigenetic information provides instructions on how, where, and when the genetic
      information should be used. The interrelationship of genetics and epigenetics is
      like a yin-yan, they are different from each other, and cooperatively take part
      in regulation of a variety of living activities. In this paper concept of gene
      and problems of evolution has been also discussed according to epigenetic
      viewpoints.

PMID- 15730977
TI  - [Genetic risks in plant ex situ conservation].
AB  - Conserving genetic diversity of rare and endangered species and their
      evolutionary potential is one of the long-term goals of ex-situ conservation.
      Some potential genetic risks in ex-situ conservation in botanical gardens are
      presented. The preserved species may lack genetic representativity because of
      poor sampling. Inappropriate plantations, inadequate records and unclear kinships
      jeopardize endangered species to genetic confusion, inbreeding depression or
      outbreeding depression. Artificial selection and habitat conversion also
      potentially result endangered plants in adapting to ex-situ conservation, which
      had been usually overlooked. All the genetic risks can decrease the success of
      reintroduction and recovery. Therefore, appropriate genetic management should be
      carried out in botanical gardens to decrease or avoid genetic risks in ex-situ
      conservation.

PMID- 15730978
TI  - [Progress of RNA interference mechanism].
AB  - RNA interference (RNAi) is a phenomenon that the double-stranded RNA (dsRNA)
      intermediates the degradation of complementary mRNA found in many organisms. This
      is a specifically mechanism involved in kinds of proteins to complete the
      interference function. Structure of siRNA affects which strand will be assembled
      into RISC. Another role of siRNA is directing RITS complex to bind with homologue
      chromosome, and then induces heterochromatinization. Although systemic silence
      induced by dsRNA is observed in Caenorhabditis elegans and plants, this progress
      is probably transmembrane protein-dependent, and mostly, the systemic silencing
      is controlled by multi-factors.

PMID- 15730980
TI  - BJR Review of the Year - 2004.

PMID- 15730981
TI  - Ultrasound-guided drainage of breast abscesses: results in 151 patients.
AB  - The aim of this paper is to describe the efficacy of ultrasound-guided drainage
      of breast abscesses with special attention to the risk of recurrence and the need
      for surgical treatment in a consecutive patient population. 151 patients, 89 with
      puerperal and 62 with non-puerperal breast abscesses, were treated with
      ultrasound-guided drainage, by needle or catheter under local anaesthesia. Follow
      up punctures were performed at 2 or 3 day intervals until the clinical condition
      and ultrasound findings had improved. All patients were treated with oral
      antibiotics. Mammography was performed to search for underlying cancer. 86 (97%)
      out of 89 patients with puerperal abscesses and 50 (81%) out of 62 with non
      puerperal abscesses recovered after the first round of ultrasound-guided
      drainage. One patient in each group had recurrence in loco but recovered after
      further ultrasound-guided drainage. 13 patients, 11 with non-puerperal and two
      with puerperal abscesses, underwent surgical excision of the abscess cavity or
      fistulas. Breastfeeding continued and 117 patients were treated as outpatients.
      The median number of follow up examinations in the ultrasound-department was four
      (range 1-10) for the group of patients with puerperal abscess and three (range 1
      7) in the group of patients with non-puerperal abscess. The corresponding figure
      for the median number of punctures was for both groups one (range 1-6 and 1-4).
      There were no reports of newly diagnosed breast cancer in the 2 year follow-up
      period. This study supports the use of ultrasound-guided drainage in puerperal
      and non-puerperal breast abscesses. The method is less invasive than traditional
      surgery and has a high rate of success.

PMID- 15730979
TI  - Vestibular perception and action employ qualitatively different mechanisms. II.
      VOR and perceptual responses during combined Tilt&Translation.
AB  - To compare and contrast the neural mechanisms that contribute to vestibular
      perception and action, we measured vestibuloocular reflexes (VOR) and perceptions
      of tilt and translation. We took advantage of the well-known ambiguity that the
      otolith organs respond to both linear acceleration and tilt with respect to
      gravity and investigated the mechanisms by which this ambiguity is resolved. A
      new motion paradigm that combined roll tilt with inter-aural translation
      ("Tilt&Translation") was used; subjects were sinusoidally (0.8 Hz) roll tilted
      but with their ears above or below the rotation axis. This paradigm provided
      sinusoidal roll canal cues that were the same across trials while providing
      otolith cues that varied linearly with ear position relative to the earth
      horizontal rotation axis. We found that perceived tilt and translation depended
      on canal cues, with substantial roll tilt and inter-aural translation perceptions
      reported even when the otolith organs measured no inter-aural force. These
      findings match internal model predictions that rotational cues from the canals
      influence the neural processing of otolith cues. We also found horizontal
      translational VORs that varied linearly with radius; a minimal response was
      measured when the otolith organs transduced little or no inter-aural force.
      Hence, the horizontal translational VOR was dependent on otolith cues but
      independent of canal cues. These findings match predictions that translational
      VORs are elicited by simple filtering of otolith signals. We conclude that
      internal models govern human perception of tilt and translation at 0.8 Hz and
      that high-pass filtering governs the human translational VOR at this same
      frequency.

PMID- 15730982
TI  - Ultrasound evaluation of the fibrosis stage in chronic liver disease by the
      simultaneous use of low and high frequency probes.
AB  - A liver biopsy is currently considered the definitive diagnostic modality for
      establishing the severity of hepatic fibrosis. We analysed the diagnostic
      sensitivity and accuracy of ultrasound (US) using both low frequency and high
      frequency probes as a repeatable, inexpensive, and reliable method to determine
      the fibrosis stage in chronic liver disease and then compared our results with
      the histological findings. A total of 103 patients with chronic liver disease (60
      males and 43 females, average age 51 years old) who had undergone both a liver
      biopsy and US with 2-5 MHz frequency and 5-12 MHz frequency probes were
      prospectively evaluated in this study. An US scoring system using both the low
      frequency and high frequency probes was performed by evaluating the edge, surface
      and parenchymal texture of the liver. Each score was obtained by evaluating three
      parameters; the bluntness of the liver edge, the irregularity of the surface and
      the coarseness of the parenchymal texture were evaluated and then compared with
      the histological findings. The US scores of the liver edge (rs: 0.6668), liver
      surface (rs: 0.9007) and liver parenchymal texture (rs: 0.8853) correlated
      significantly with the fibrosis stage obtained based on the biopsy findings. The
      accumulated US scores of these three parameters, however, was found to be the
      most reliable indicator (rs: 0.9524). Patients with an accumulated score of 6.5
      or more were all found to have fibrosis stage 4 in which the accuracy of our
      scoring system for correctly predicting cirrhosis was found to be 100% sensitive.
      When an accumulated US score of 3 was interpreted to indicate mild fibrosis (a
      fibrosis score of 0 or 1), all 42 patients with stage 0 or 1 fibrosis were found
      to have an accumulated US score of 3 or less (a probability of 100%) and 42 of 53
      patients with a score of 3 or less were found to have stage 0 or 1 fibrosis
      (specificity of 79.2%). An ultrasound evaluation of the liver fibrosis stage
      based on the scoring system using both low and high frequency probes was found to
      be a reliable and effective alternative to the histological staging in chronic
      liver diseases.

PMID- 15730983
TI  - A comparative study of evaluation of radiographs, CT and 3D reformatted CT in
      facial trauma: what is the role of 3D?
AB  - A panel of 17 trainee maxillofacial surgeons viewed 23 cases of facial trauma,
      demonstrated on radiographs, axial CT images and three-dimensional (3D)
      reformatted CT images in a standardized viewing format under standard conditions.
      Their diagnostic interpretation, extraction of information relevant to surgical
      management and subjective evaluation of each modality were recorded by standard
      questionnaire and compared with a gold standard evaluation by a consultant
      radiologist and surgeon reading based on results of clinical management. There
      were clear and measurable differences in the viewers' evaluations of radiographs,
      CT and 3D reformatted images. Overall, surgeons showed more accurate diagnostic
      reading of radiographs and 3D reformatted images. This was in contrast to their
      subjective assessment of the clinical value of each modality, which showed a
      strong preference for 3D over all other techniques and for CT over radiographs.
      However the perceived benefit of axial CT images over radiographs was not
      reproduced on objective testing in this group; surgeons appear to perform less
      well in interpreting CT images than their subjective response to the modality
      would suggest. This work has supported the view that surgeons value 3D imaging as
      a front-line tool in the evaluation and management of selected cases of acute
      facial trauma. We have demonstrated that the perceived benefits of 3D reformatted
      CT to surgeons appear real.

PMID- 15730985
TI  - Radiation doses received in the UK Breast Screening Programme in 2001 and 2002.
AB  - The mean glandular doses (MGD) to samples of women attending for mammographic
      screening are measured routinely at screening centres in the UK Breast Screening
      Programme (NHSBSP). This paper reviews a large representative sample of dose
      measurements collected during screening in the NHSBSP in 2001 and 2002 for 53 218
      films, using 290 X-ray sets, for 16 505 women. The average MGD was 2.23 mGy per
      oblique film and 1.96 mGy per craniocaudal film; similar to those found
      previously in the NHSBSP for the years 1997 and 1998. Increasing use of
      sophisticated units with automatic beam quality selection has reduced the
      radiation dose received by large breasts, with only 2% of oblique mammograms
      having doses in excess of 5 mGy. The increasing use of large format film has also
      reduced the doses to this sub-group. However the total dose per woman has
      increased due to the introduction of two view screening at every visit. The MGD
      to the standard breast was found to vary from 0.76 mGy to 2.29 mGy, with 97% of
      units below the recommended upper limit of 2 mGy, illustrating the benefit of
      strict quality control. A reduction in dose of 3% was observed between the age
      bands 50-54 years and 60-64 years. This study has confirmed that the proposed
      national diagnostic reference level (NDRL) of 3.5 mGy for 55 mm thick breasts is
      an appropriate value to identify systems giving unusually high doses, with just
      3.5% of systems exceeding this level. In most cases these higher doses were
      explained by the design of one particular make of X-ray set and its mode of
      operation. Average doses for oblique views of average sized breasts were fairly
      well correlated with the dose to the standard breast, and typically 42% higher.
      This highlights the need for a revised definition of the standard breast used in
      the UK to better reflect the exposure factors and doses received in clinical
      practice.

PMID- 15730984
TI  - MR colonography: baseline appearance of the unprepared rectosigmoid.
AB  - A retrospective review of 100 routine pelvic MR examinations was conducted to
      evaluate the appearance of the unprepared rectosigmoid colon, with the aim of
      informing future strategies for minimal preparation MR colonography. All
      examinations were reviewed by two observers in consensus, and included matched
      location axial T1 weighted and T2 weighted fat suppressed fast spin echo (FSFSE)
      images. Analysis revealed that the overall appearance of the faecal material in
      the colon could simulate tumour in 80% of T1 weighted and 17% of T2 weighted
      images. By matching the images from the two sequences for each patient the faeces
      had an overall appearance that would mimic tumour in only 7% of cases. However,
      luminal tumour-mimicking foci of signal occurred frequently, present in 91% of T1
      weighted and 85% of T2 weighted studies. The results indicate that if bowel
      cleansing regimens are to be avoided for MR colonography, effective strategies
      such as dietary restriction and use of oral contrast agents will be required to
      reduce luminal signal on T2 weighting and eliminate polyp-mimicking foci. The
      results also suggest that T2 weighted strategies should be further investigated
      and that combination with T1 weighted imaging may improve discrimination of
      lesions from normal faecal material.

PMID- 15730986
TI  - A study of the distribution of dose across the hands of interventional
      radiologists and cardiologists.
AB  - The magnitude and distribution of doses across the hands of interventional
      radiologists and cardiologists have been studied. The aims were to determine the
      region of highest dose, investigate variations in dose distribution, and propose
      an effective method for dose monitoring. Doses have been measured using sets of
      up to 18 thermoluminescent dosemeters (TLDs) for 183 single procedures. Important
      factors influencing the dose to the hand are the type of procedure, particularly
      the access route, the X-ray equipment used, and the experience of the operator.
      Radiologists performing percutaneous procedures received the highest doses,
      because of the proximity of their hands to the X-ray tube. The majority of
      procedures involve a combination of twisting and prodding actions, and the
      relative proportions of each determine the parts of the fingers which receive a
      higher dose. For most interventional radiology and cardiology procedures the
      bases of the ring and little fingers receive the highest dose. However, during
      percutaneous procedures the tips of the middle and ring fingers could receive
      doses which were 20-30% higher than this. For radiologists and cardiologists with
      a mixed workload, monitoring using TLD rings located at the base of the little or
      the ring fingers on either hand should provide a reasonable estimate of dose to
      the most exposed area. Monitoring is recommended for operators who may receive
      over 50 mSv to their hands per year, and should be considered for operators
      carrying out therapeutic procedures involving patient dose-area products over 500
      Gy cm2 per month.

PMID- 15730987
TI  - Treatment outcomes and prognostic factors in patients with supratentorial low
      grade gliomas.
AB  - Low-grade gliomas account for 10-15% of all adult primary intracranial tumours.
      Currently, there is no consensus on the treatment strategy for low-grade gliomas.
      This study was designed to evaluate the treatment outcomes, prognostic factors
      and radiation-related late complications, as well as to assess whether or not
      post-operative radiotherapy has benefit on local control and overall survival in
      this population. We retrospectively reviewed 93 consecutive adult patients with
      supratentorial low-grade gliomas diagnosed at our institution from July 1985 to
      December 1997. All patients underwent surgical intervention and 60 of them
      received post-operative radiotherapy. With a median follow-up of 110 months for
      surviving patients, the 5-year overall and progression-free survival rates were
      57% and 47%, respectively. 46 patients experienced local progression of disease
      during the follow-up period. In multivariate analysis, age at diagnosis, extent
      of surgery and post-operative Karnofsky performance status showed independent
      prognostic significance for progression-free and overall survival rates. Post
      operative radiotherapy had independent prognostic value for progression-free
      survival. This analysis has changed our practice and we suggest that aggressive
      surgical resection and post-operative radiotherapy might be considered for
      patients with low-grade gliomas. Further efforts should be made to optimize
      radiotherapy techniques and to integrate new therapeutic modalities.

PMID- 15730988
TI  - Daytime pulsed dose rate brachytherapy as a new treatment option for previously
      irradiated patients with recurrent oesophageal cancer.
AB  - The aim of this study was to evaluate the feasibility, effects, and toxicity of
      pulsed dose rate (PDR) brachytherapy for re-irradiation of oesophageal carcinoma.
      A total of 16 patients (median age 67 years) with inoperable recurrences from
      oesophageal cancer after primary radio-(chemo)-therapy (median 50 Gy) were re
      irradiated using PDR brachytherapy ((192)Ir, 37 GBq). Treatment was carried out
      on an outpatient basis applying a weekly 5 Gy daytime schedule (0.5 Gy pulse(-1)
      h(-1), total dose 15-20 Gy). The dose was prescribed 10 mm from the mid-dwell
      position and encompassed the clipped tumour extension with 2 cm margins. The use
      of clips for delineation of tumour extent and catheter movement during
      irradiations was evaluated. All 61 PDR treatments were applied safely. The median
      catheter movement was 5 mm, range 2-12 mm. After a median follow-up of 8 months,
      three patients had a complete and five a partial remission. Body weight increased
      in 5 of 16 (31%) and was stable in 4 of 16 (25%) patients, respectively. The
      median grade 2 (RTOG/EORTC) dysphagia-free survival was 17 months. Seven patients
      experienced grade 1, five grade 2, and one grade 3 late toxicity. Three patients
      with uncontrolled locoregional disease showed grade 4 complications (oesophago
      tracheal fistulae (n=2), fatal arterial bleeding (n=1). Daytime PDR brachytherapy
      proved to be feasible and provided effective palliation. Toxicity remains a major
      problem. Thus, total dose should be restricted to <15 Gy in this palliative
      situation.

PMID- 15730989
TI  - Abnormal hepatic vein Doppler waveform in patients without liver disease.
AB  - In patients with liver cirrhosis Doppler ultrasound often detects absence of the
      retrograde (hepatopetal) flow phase in the hepatic vein, suggestive of an
      increased stiffness of the liver parenchyma around the vein. This is rarely or
      never reported in healthy control persons. We examined the frequency of absent
      retrograde flow in a consecutive series of 139 patients referred for abdominal
      ultrasound. We used state-of-the-art ultrasound scanners, and placed the Doppler
      gate so that in non-forced end-expiration it would sample the right hepatic vein
      4-6 cm from the vena cava. There was no association between the hepatic vein flow
      pattern and age, sex or body mass index. 43 of 139 studied patients showed absent
      retrograde flow. Review of the case records revealed liver disease in 26 patients
      and no sign of liver disease in 17 patients. We suggest that absent retrograde
      flow in the hepatic veins may be seen not only in patients with overt liver
      disease but also in apparently liver-healthy patients.

PMID- 15730990
TI  - Techniques and trouble-shooting in high spatial resolution thin slice MRI for
      rectal cancer.
AB  - MRI is increasingly advocated as an optimal method of staging rectal cancer. The
      technique enables depiction of the relationship of tumour to the mesorectal
      fascia and may thus identify tumours at risk of positive circumferential margin
      involvement at surgery. Depth of extramural spread may also be accurately
      measured and tumour deposits within the mesorectum are shown. It is important
      that a high spatial resolution technique is used in order to accurately depict
      these features and care should be taken in ensuring that images acquired cover
      the entire rectal tumour and mesorectum. This paper describes the technique of
      high spatial resolution rectal cancer imaging and the potential technical
      pitfalls in acquiring good quality images. Important factors to consider include:
      adequate scan duration to achieve high spatial resolution images with sufficient
      signal to noise ratio, careful positioning of the pelvic phased array coil, use
      of T2 weighted turbo spin-echo rather than T1 weighted imaging and careful
      planning of scans to ensure that images are obtained perpendicular to the rectal
      wall.

PMID- 15730991
TI  - Selective conformal radiotherapy for arteriovenous malformation involving the
      spinal cord.
AB  - Radiotherapy has seldom been used in the treatment of arteriovenous malformations
      (AVM) involving the spinal cord because of the cord's limited radiation
      tolerance. A 57-year-old woman with progressive myelopathy due to AVM was treated
      with a selective conformal radiation therapy (55.6 Gy/20 days) on the nidus
      region preserving the spinal cord, drainer veins and involved bones. The drainers
      and symptoms were minimized at the end of treatment and disappeared over 2 years.
      This case illustrates the usefulness of selective conformal radiation therapy.

PMID- 15730992
TI  - Small cell carcinoma of the colon: barium study and CT findings.
AB  - Extrapulmonary small cell carcinoma is a rare neoplasm. It is an aggressive
      malignant tumour characterized by rapid local progression and early metastasis.
      We report a case of small cell carcinoma arising in the transverse colon in a 34
      year-old man who presented with epigastric pain. On CT, a poorly enhancing bulky
      mass encircling the transverse colon with extensive regional lymph node
      metastases was observed. A segmental annular narrowing with thick interhaustral
      folds of the transverse colon was found by barium enema examination. This is the
      first report of barium study and CT findings of extrapulmonary small cell
      carcinoma of the colon.

PMID- 15730993
TI  - Pilomatrix carcinoma of the axilla: CT and MRI features.
AB  - Pilomatrix carcinoma, a rare malignant soft tissue tumour, is the malignant
      variant of pilomatricoma. We report a case of pilomatrix carcinoma of the axilla.
      CT demonstrated a well-circumscribed, sand-like calcified mass. MRI showed
      diffusely inhomogeneous, mixed signal intensities with inhomogeneous
      enhancements. The MRI findings were different from those previously reported for
      pilomatricoma.

PMID- 15730994
TI  - Successful treatment of a chronic post-traumatic 5-year-old osteoporotic
      vertebral compression fracture by percutaneous vertebroplasty.
AB  - Osteoporotic vertebral compression fracture (VCF) is a frequently encountered
      clinical problem associated with chronic pain and disability. Conservative
      treatment in the form of bed rest, pain control and bracing may create a vicious
      circle, in which reduced activity leads to further reduction in bone density and
      fracture risk. Percutaneous vertebroplasty (PVP) is an accepted treatment
      modality for osteoporotic vertebral body collapse present for less than 1 year,
      vertebral myeloma, haemangioma, metastasis and recent traumatic fractures
      (between 3 and 12 months). We describe an osteoporotic patient in whom successful
      PVP was performed, under general anaesthesia using CT and fluoroscopic guidance,
      in a post-traumatic 5-year-old VCF with complete alleviation of debilitating
      pain. In the light of our experience, we suggest that PVP should be carried out
      in a series of similar patients to asses its value as a treatment option in
      patients with chronic osteoporotic vertebral fractures for pain relief and
      improvement in mobility, independent of fracture age.

PMID- 15730995
TI  - Pseudocyst rupture into the portal vein diagnosed with MRI.
AB  - We report on the first documented case of rupture of a pancreatic pseudocyst into
      the portal vein diagnosed with MRI.

PMID- 15730996
TI  - Erythropoietin-producing renal cell carcinoma arising from autosomal dominant
      polycystic kidney disease.
AB  - Erythropoietin (EPO)-producing renal cell carcinomas (RCC) in patients with
      chronic renal failure secondary to autosomal dominant polycystic kidney disease
      (ADPKD) has not previously been reported. We report a case of EPO-producing RCC
      associated with ADPKD in a 66-year-old woman, and discuss the clinical and
      radiological findings.

PMID- 15730997
TI  - Non-infectious manifestations of stem cell transplantation.
AB  - Stem cell transplantation (SCT) is now commonplace within medical practice. With
      growth in transplant activities, outcomes are likely to continue to improve.
      Increasing numbers of the population now face life after transplantation. The
      aetiology of post transplant complications is multifactorial. Background
      knowledge of SCT and common, radiographically detectable, non-infective
      complications are important in everyday clinical practice. A review of these
      complications using a variety of imaging modalities is presented and the process
      of SCT briefly described. Tumour recurrence is outside the remit of this review.

PMID- 15730998
TI  - Whispering enigma.

PMID- 15730999
TI  - Posterior fossa treatment.

PMID- 15731001
TI  - The Ras superfamily at a glance.

PMID- 15731002
TI  - PML bodies: a meeting place for genomic loci?
AB  - Promyelocytic leukemia (PML) bodies have been implicated in a variety of cellular
      processes, such as cell-cycle regulation, apoptosis, proteolysis, tumor
      suppression, DNA repair and transcription. Despite this, the function of PML
      bodies is still unknown. Direct and indirect evidence supports the hypothesis
      that PML bodies interact with specific genes or genomic loci. This includes the
      finding that the stability of PML bodies is affected by cell stress and changes
      in chromatin structure. PML bodies also facilitate the transcription and
      replication of double-stranded DNA viral genomes. Moreover, PML bodies associate
      with specific regions of high transcriptional activity in the cellular genome. We
      propose that PML bodies functionally interact with chromatin and are important
      for the regulation of gene expression.

PMID- 15731003
TI  - Another dimension to calcium signaling: a look at extracellular calcium.
AB  - Cell biologists know the calcium ion best as a vital intracellular second
      messenger that governs countless cellular functions. However, the recent
      identification of cell-surface detectors for extracellular Ca(2+) has prompted
      consideration of whether Ca(2+) also functions as a signaling molecule in the
      extracellular milieu. The cast of Ca(2+) sensors includes the well-characterized
      extracellular-Ca(2+)-sensing receptor, a G-protein-coupled receptor originally
      isolated from the parathyroid gland. In addition, other receptors, channels and
      membrane proteins, such as gap junction hemichannels, metabotropic glutamate
      receptors, HERG K(+) channels and the receptor Notch, are all sensitive to
      external [Ca(2+)] fluctuations. A recently cloned Ca(2+) sensor (CAS) in
      Arabidopsis extends this concept to the plant kingdom. Emerging evidence
      indicates that [Ca(2+)] in the local microenvironment outside the cell undergoes
      alterations potentially sufficient to exert biological actions through these
      sensor proteins. The extracellular space might therefore constitute a much more
      dynamic Ca(2+) signaling compartment than previously appreciated.

PMID- 15731004
TI  - Re-establishing the regenerative potential of central nervous system axons in
      postnatal mice.
AB  - At a certain point in development, axons in the mammalian central nervous system
      lose their ability to regenerate after injury. Using the optic nerve model, we
      show that this growth failure coincides with two developmental events: the loss
      of Bcl-2 expression by neurons and the maturation of astrocytes. Before postnatal
      day 4, when astrocytes are immature, overexpression of Bcl-2 alone supported
      robust and rapid optic nerve regeneration over long distances, leading to
      innervation of brain targets by day 4 in mice. As astrocytes matured after
      postnatal day 4, axonal regeneration was inhibited in mice overexpressing Bcl-2.
      Concurrent induction of Bcl-2 and attenuation of reactive gliosis reversed the
      failure of CNS axonal re-elongation in postnatal mice and led to rapid axonal
      regeneration over long distances and reinnervation of the brain targets by a
      majority of severed optic nerve fibers up to 2 weeks of age. These results
      suggest that an early postnatal downregulation of Bcl-2 and post-traumatic
      reactive gliosis are two important elements of axon regenerative failure in the
      CNS.

PMID- 15731005
TI  - Changing chromatin dynamics and nuclear organization during differentiation in
      Drosophila larval tissue.
AB  - Global changes in gene expression and exit from the cell cycle underlie
      differentiation. Therefore, understanding chromatin behavior in differentiating
      nuclei and late G1 is key to understanding this developmental event. A nuclear
      event that has been shown to specifically occur in late G1 is the association of
      two heterochromatic blocks in Drosophila. The brown(Dominant) (bw(D)) chromosome
      of Drosophila melanogaster contains a large block of heterochromatin near the end
      of 2R. This distal block associates with centric heterochromatin (2Rh), but not
      until at least 5 hours into G1. We used the bw(D) allele as a model for nuclear
      organization to determine whether its association with the heterochromatic
      compartment of the second chromosomes (2Rh) strictly requires differentiation or
      if this change is a stochastic event, its occurrence being proportional to time
      spent in G1/G0 phase of the cell cycle. Fluorescence in situ hybridization on eye
      imaginal discs showed increased association between the bw locus and 2Rh in
      differentiated cells. Interestingly, an increase in the number of nuclei showing
      bw(D)-2Rh association in the brains of developmentally delayed larvae that were
      compromised for differentiation was also observed. Live fluorescence imaging
      showed that the kinetics of chromatin movement remains unchanged in the
      developmentally arrested nuclei. These observations suggest that nuclear
      reorganization is not directly controlled by specific inductive signals during
      differentiation and that this nuclear reorganization can happen in a cell,
      regardless of differentiation state, that is arrested in the appropriate cell
      cycle stage. However, we did see changes that appear to be more directly
      correlated with differentiation. Dynamic imaging in eye imaginal discs showed
      that the movement of chromatin is more constrained in differentiated cells,
      implying that confinement of loci to a smaller nuclear space may help to maintain
      the changed organization and the transcription profile that accompanies
      differentiation.

PMID- 15731006
TI  - The translational regulator CPEB1 provides a link between dcp1 bodies and stress
      granules.
AB  - The cytoplasmic polyadenylation element-binding protein (CPEB) has been
      characterized in Xenopus laevis as a translational regulator. During the early
      development, it behaves first as an inhibitor and later as an activator of
      translation. In mammals, its closest homologue is CPEB1 for which two isoforms,
      short and long, have been described. Here we describe an additional isoform with
      a different RNA recognition motif, which is differentially expressed in the brain
      and ovary. We show that all CPEB1 isoforms are found associated with two
      previously described cytoplasmic structures, stress granules and dcp1 bodies.
      This association requires the RNA binding ability of the protein, whereas the
      Aurora A phosphorylation site is dispensable. Interestingly, the rck/p54 DEAD box
      protein, which is known as a CPEB partner in Xenopus and clam, and as a component
      of dcp1 bodies in mammals, is also present in stress granules. Both stress
      granules and dcp1 bodies are involved in mRNA storage and/or degradation,
      although so far no link has been made between the two, in terms of neither
      morphology nor protein content. Here we show that transient CPEB1 expression
      induces the assembly of stress granules, which in turn recruit dcp1 bodies. This
      dynamic connection between the two structures sheds new light on the
      compartmentalization of mRNA metabolism in the cytoplasm.

PMID- 15731007
TI  - Glycogen synthase kinase-3beta phosphorylation of MAP1B at Ser1260 and Thr1265 is
      spatially restricted to growing axons.
AB  - Recent experiments show that the microtubule-associated protein (MAP) 1B is a
      major phosphorylation substrate for the serine/threonine kinase glycogen synthase
      kinase-3beta (GSK-3beta) in differentiating neurons. GSK-3beta phosphorylation of
      MAP1B appears to act as a molecular switch regulating the control that MAP1B
      exerts on microtubule dynamics in growing axons and growth cones. Maintaining a
      population of dynamically unstable microtubules in growth cones is important for
      axon growth and growth cone pathfinding. We have mapped two GSK-3beta
      phosphorylation sites on mouse MAP1B to Ser1260 and Thr1265 using site-directed
      point mutagenesis of recombinant MAP1B proteins, in vitro kinase assays and
      phospho-specific antibodies. We raised phospho-specific polyclonal antibodies to
      these two sites and used them to show that MAP1B is phosphorylated by GSK-3beta
      at Ser1260 and Thr1265 in vivo. We also showed that in the developing nervous
      system of rat embryos, the expression of GSK-3beta phosphorylated MAP1B is
      spatially restricted to growing axons, in a gradient that is highest distally,
      despite the expression of MAP1B and GSK-3beta throughout the entire neuron. This
      suggests that there is a mechanism that spatially regulates the GSK-3beta
      phosphorylation of MAP1B in differentiating neurons. Heterologous cell
      transfection experiments with full-length MAP1B, in which either phosphorylation
      site was separately mutated to a valine or, in a double mutant, in which both
      sites were mutated, showed that these GSK-3beta phosphorylation sites contribute
      to the regulation of microtubule dynamics by MAP1B.

PMID- 15731008
TI  - MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder
      Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis.
AB  - Chaperonins are multisubunit, cylinder-shaped molecular chaperones involved in
      folding newly synthesized polypeptides. Here we show that MKKS/BBS6, one of
      several proteins associated with Bardet-Biedl syndrome (BBS), is a Group II
      chaperonin-like protein that has evolved recently in animals from a subunit of
      the eukaryotic chaperonin CCT/TRiC, and diverged rapidly to acquire distinct
      functions. Unlike other chaperonins, cytosolic BBS6 does not oligomerize, and the
      majority of BBS6 resides within the pericentriolar material (PCM), a
      proteinaceous tube surrounding centrioles. During interphase, BBS6 is confined to
      the lateral surfaces of the PCM but during mitosis it relocalizes throughout the
      PCM and is found at the intercellular bridge. Its predicted substrate-binding
      apical domain is sufficient for centrosomal association, and several patient
      derived mutations in this domain cause mislocalization of BBS6. Consistent with
      an important centrosomal function, silencing of the BBS6 transcript by RNA
      interference in different cell types leads to multinucleate and multicentrosomal
      cells with cytokinesis defects. The restricted tissue distribution of BBS6
      further suggests that it may play important roles in ciliated epithelial tissues,
      which is consistent with the probable functions of BBS proteins in basal bodies
      (modified centrioles) and cilia. Our findings provide the first insight into the
      nature and cellular function of BBS6, and shed light on the potential causes of
      several ailments, including obesity, retinal degeneration, kidney dysfunction and
      congenital heart disease.

PMID- 15731009
TI  - Ste20/GCK kinase Nak1/Orb3 polarizes the actin cytoskeleton in fission yeast
      during the cell cycle.
AB  - Polar growth is a crucial process during cell morphogenesis. The microtubule and
      actin cytoskeletons, and vesicular transport are tightly regulated to direct
      cellular growth and to generate specific cell forms. We demonstrate here that the
      Ste20-related protein kinase Nak1/Orb3 is required in fission yeast to polarize
      the actin cytoskeleton at the tips of the cells and for cell separation, and so
      is involved in controlling both cell shape and late stages of cytokinesis. The
      localization of the Nak1/Orb3 kinase to the cell tips, a medial ring and the
      spindle-pole bodies changes during the cell cycle, and the accumulation of F
      actin at the cell tips is dependent on Nak1/Orb3 kinase. The phosphorylation of
      Nak1/Orb3 is periodic during the cell cycle and could be part of a mechanism that
      relocalizes a constitutively active kinase from the cell tips to the middle of
      the cell, thereby coordinating reorganization of the actin cytoskeleton and
      regulation of cell separation with cell-cycle progression.

PMID- 15731010
TI  - Keratinocytes display normal proliferation, survival and differentiation in
      conditional beta4-integrin knockout mice.
AB  - The alpha6beta4 integrin is located at the basal surface of keratinocytes, in
      hemidesmosomal structures that mediate stable adhesion of epidermal cells to the
      underlying basement membrane component laminin-5. The absence of alpha6beta4
      integrin causes junctional epidermolysis bullosa, a severe blistering disease of
      the skin leading to perinatal death, confirming its essential role in mediating
      strong keratinocyte adhesion. Several studies have suggested that alpha6beta4
      integrin can also regulate signaling cascades that control cell proliferation,
      survival and migration through a mechanism independent of its adhesive function.
      We have generated a conditional knockout mouse strain, in which the gene encoding
      the beta4 integrin subunit (Itgb4) was inactivated only in small stretches of the
      skin. These mice were viable and permitted an accurate analysis of the
      consequences of the loss of beta4 on various biological processes by comparing
      beta4-positive and -negative parts of the skin in the same animal. Despite the
      complete loss of hemidesmosomes in regions lacking alpha6beta4 integrin, the
      distribution of a range of adhesion receptors and basement membrane proteins was
      unaltered. Moreover, loss of alpha6beta4 did not affect squamous differentiation,
      proliferation or survival, except for areas in which keratinocytes had detached
      from the basement membrane. These in vivo observations were confirmed in vitro by
      using immortalized keratinocytes - derived from beta4-subunit conditional
      knockout mice - from which the gene encoding beta4 had been deleted by Cre
      mediated recombination. Consistent with the established role of alpha6beta4 in
      adhesion strengthening, its loss from cells was found to increase their motility.
      Our findings clearly demonstrate that, after birth, epidermal differentiation,
      proliferation and survival all proceed normally in the absence of alpha6beta4,
      provided that cell adhesion is not compromised.

PMID- 15731011
TI  - Proteasome inhibition activates the transport and the ectodomain shedding of TNF
      alpha receptors in human endothelial cells.
AB  - Binding of tumor necrosis factor-alpha (TNF-alpha) to its transmembrane receptors
      (TNFRs) mediates proinflammatory, apoptotic and survival responses in several
      cell types including vascular endothelial cells. Because ectodomain shedding of
      cell surface molecules can be modified by proteasome activity, we studied in
      human endothelial cells whether the TNF-alpha-TNFRs axis can be regulated by the
      cleavage of their transmembrane forms in a proteasome-dependent manner. We show
      that proteasome inhibition increases the release of TNF-alpha and TNFRs from
      human endothelial cells and decreases their cellular and cell surface expression.
      This phenomenon involves the transient activation of mitogen-activated protein
      kinase p42/p44 that triggers the dispersion of TNF-alpha and TNFRs from their
      intracellular Golgi-complex-associated pool towards the plasma membrane. This
      results in their enhanced cleavage by TNF-alpha converting enzyme (TACE) because
      it is reduced by synthetic metalloprotease inhibitors, recombinant TIMP-3 and by
      a dominant negative form of TACE. In the presence of TACE inhibitor, proteasome
      inhibition increases the cell surface expression of TNFRs and enhances the
      sensitivity of these cells to the proapoptotic effect of recombinant TNF-alpha.
      In conclusion, our data provide evidence that proteasome inhibitors increase TACE
      dependent TNFR-shedding in endothelial cells, supporting the use of these
      molecules in inflammatory disorders. In association with TACE inhibitor,
      proteasome inhibitors increase the amount of TNFRs at the cell surface and
      enhance the sensitivity to the proapoptotic effect of TNF-alpha, which might be
      of interest in the antitumor therapy.

PMID- 15731012
TI  - The chemokine SDF-1 differentially regulates axonal elongation and branching in
      hippocampal neurons.
AB  - Recent data have shown that the chemokine SDF-1 plays a critical role in several
      aspects of brain development such as cell migration and axon pathfinding.
      However, its potential function in the generation of axons and dendrites is
      poorly characterized. In order to better understand the role of SDF-1 in the
      development of central neurons, we studied the cellular distribution of the SDF-1
      receptor CXCR4 by immunocytochemistry of developing hippocampal neurons and
      tested the effect of SDF-1 in process patterning at the early stages of neuronal
      development. We found that CXCR4 immunoreactivity undergoes a striking
      redistribution during development. At the early stages, from day 2 to day 4 in
      culture, CXCR4 is particularly concentrated at the leading edge of growing
      neurites. As the cells mature, staining declines at the tip of the processes and
      becomes more broadly distributed along axons and, to a lesser extent, dendrites.
      SDF-1 stimulation of neurons at day 1-2 in culture triggers several effects on
      neuronal morphogenesis. SDF-1 reduces growth cone number and axonal outgrowth but
      stimulates axonal branching. These latter two effects are not observed in other
      neurites. This study unravels a new role for SDF-1/CXCR4 in specifying
      hippocampal neuron morphology by regulating axonal patterning at an early stage
      of neuronal development.

PMID- 15731013
TI  - Identification of trichoplein, a novel keratin filament-binding protein.
AB  - Keratins 8 and 18 (K8/18) are major components of the intermediate filaments
      (IFs) of simple epithelia. We report here the identification of a novel protein
      termed trichoplein. This protein shows a low degree of sequence similarity to
      trichohyalin, plectin and myosin heavy chain, and is a K8/18-binding protein.
      Among interactions between trichoplein and various IF proteins that we tested
      using two-hybrid methods, trichoplein interacted significantly with K16 and K18,
      and to some extent with K5, K6a, K8 and K14. In in vitro co-sedimentation assays,
      trichoplein directly binds to K8/18, but not with vimentin, desmin, actin
      filaments or microtubules. An antibody raised against trichoplein specifically
      recognized a polypeptide with a relative molecular mass of 61 kDa in cell
      lysates. Trichoplein was immunoprecipitated using this antibody in a complex with
      K8/18 and immunostaining revealed that trichoplein colocalized with K8/18
      filaments in HeLa cells. In polarized Caco-2 cells, trichoplein colocalized not
      only with K8/18 filaments in the apical region but also with desmoplakin, a
      constituent of desmosomes. In the absorptive cells of the small intestine,
      trichoplein colocalized with K8/18 filaments at the apical cortical region, and
      was also concentrated at desmosomes. Taken together, these results suggest that
      trichoplein is a keratin-binding protein that may be involved in the organization
      of the apical network of keratin filaments and desmosomes in simple epithelial
      cells.

PMID- 15731014
TI  - Band 3 modifications in Plasmodium falciparum-infected AA and CC erythrocytes
      assayed by autocorrelation analysis using quantum dots.
AB  - The molecular stability of hemoglobin is critical for normal erythrocyte
      functions, including oxygen transport. Hemoglobin C (HbC) is a mutant hemoglobin
      that has increased oxidative susceptibility due to an amino acid substitution
      (beta6: Glu to Lys). The growth of Plasmodium falciparum is abnormal in
      homozygous CC erythrocytes in vitro, and CC individuals show innate protection
      against severe P. falciparum malaria. We investigated one possible mechanism of
      innate protection using a quantum dot technique to compare the distribution of
      host membrane band 3 molecules in genotypically normal (AA) to CC erythrocytes.
      The high photostability of quantum dots facilitated the construction of 3D cell
      images and the quantification of fluorescent signal intensity. Power spectra and
      1D autocorrelation analyses showed band 3 clusters on the surface of infected AA
      and CC erythrocytes. These clusters became larger as the parasites matured and
      were more abundant in CC erythrocytes. Further, average cluster size (500 nm) in
      uninfected (native) CC erythrocytes was comparable with that of parasitized AA
      erythrocytes but was significantly larger (1 microm) in parasitized CC
      erythrocytes. Increased band 3 clustering may enhance recognition sites for
      autoantibodies, which could contribute to the protective effect of hemoglobin C
      against malaria.

PMID- 15731015
TI  - X-ray imaging physics for nuclear medicine technologists. Part 2: X-ray
      interactions and image formation.
AB  - The purpose is to review in a 4-part series: (i) the basic principles of x-ray
      production, (ii) x-ray interactions and data capture/conversion, (iii)
      acquisition/creation of the CT image, and (iv) operational details of a modern
      multislice CT scanner integrated with a PET scanner. In part 1, the production
      and characteristics of x-rays were reviewed. In this article, the principles of x
      ray interactions and image formation are discussed, in preparation for a general
      review of CT (part 3) and a more detailed investigation of PET/CT scanners in
      part 4.

PMID- 15731016
TI  - Fundamentals of ICANL accreditation.
AB  - The Intersocietal Commission for the Accreditation of Nuclear Medicine
      Laboratories (ICANL) has become a nationally recognized accreditation program
      with the primary goal of providing a multidisciplinary peer review program. The
      purpose of this paper is to review the structure and mission of the ICANL to help
      increase awareness of the importance of voluntary accreditation. Included is a
      broad review of the ICANL standards and their relationship to other nationally
      published standards and guidelines. A mandatory site visit is an integral part of
      the program, and specifics of the site visit are discussed along with a summary
      of the strengths and weaknesses of applicant laboratories. The benefits of
      voluntary accreditation will become clear as more facilities participate in the
      program.

PMID- 15731017
TI  - Outpatient therapeutic 131I for thyroid cancer.
AB  - OBJECTIVE: We retrospectively analyzed the safety, cost effectiveness, and
      patient acceptance of outpatient high-dose 131I treatment for thyroid cancer at
      our hospital since 1997, when the Nuclear Regulatory Commission began allowing
      high-dose outpatient therapy with radioiodine. METHODS: Forty-eight patients were
      treated as outpatients because their living conditions were acceptable and they
      were willing to comply with radiation safety guidelines. The homes of 3 patients
      were surveyed for contamination. The cost of outpatient treatment was compared
      with the cost of inpatient treatment. Patient acceptance was assessed by patient
      satisfaction surveys performed at the time of the posttherapy scan. RESULTS: No
      levels of contamination above regulatory levels were found in patients' homes.
      The cost of outpatient treatment was favorable. All surveyed patients were
      pleased with the procedure. CONCLUSION: If state and federal guidelines for
      releasing patients are followed, and if patients' living conditions are
      adequately assessed, outpatient treatment with high-dose 131I is safe and cost
      effective and improves patient satisfaction.

PMID- 15731018
TI  - Small urine leak after renal transplantation: detection by delayed 99mTc-DTPA
      renography--a case report.
AB  - This case report involves a 45-y-old woman after cadaveric renal transplantation.
      The initial renal scan on the first postsurgical day showed normal findings.
      Subsequently, on the sixth postsurgical day, the patient had decreased urine
      output; 99mTc-diethylenetriaminepentaacetic acid renal scanning was performed
      again and did not show definite scintigraphic evidence of a urine leak. The
      patient's condition was not improving; renal scanning was repeated on day 20 and
      demonstrated a large photopenic region surrounding the superior, medial, and
      inferior aspects of the kidney. Delayed imaging was performed 2.5 h after
      injection of radiotracer, and activity was observed in the previously cold
      region.

PMID- 15731019
TI  - The effect of selected preparation variables on the radiochemical purity of 99mTc
      sestamibi.
AB  - OBJECTIVE: Measurement of cardiac perfusion via agents such as 99mTc-sestamibi
      (Cardiolite; DuPont-Merck Pharmaceutical Co., Inc.) is widely used in clinical
      nuclear medicine for the diagnosis of coronary artery disease. The monograph for
      99mTc-sestamibi recommends at least 90% radiochemical purity (RCP) for clinical
      use. Various factors may influence the RCP of certain reagent kits. Some of these
      include the amount of activity added to the reagent kit, the generator ingrowth
      time, the generator manufacturer, the age of the eluate, and the age of the
      formulated kit. A D-optimal design with a 20-experiment run was devised to study
      the effects of these variables either alone or in combination on the RCP of 99mTc
      sestamibi. METHODS: The RCP was assessed by Baker-Flex thin-layer and high
      performance liquid chromatographic methods, immediately and 6 h after
      reconstitution of the 99mTc-sestamibi. RESULTS: The results showed that 4 of the
      5 variables studied were statistically significant predictors of the RCP. The age
      of the formulated kit did not influence the RCP. CONCLUSION: For any combination
      of these 4 variables, the mean RCP remained greater than or equal to 90%, that
      is, within the recommended range of RCP for clinical use at radioactivity levels
      ranging from 5,550 MBq to 37,000 MBq.

PMID- 15731020
TI  - False-positive "necklace sign" on whole-body thyroid cancer survey--a case
      report.
AB  - A woman with papillary thyroid carcinoma treated with surgery and postoperative
      131I returned 4 y later for a whole-body survey. The imaging results initially
      suggested disease recurrence but were later found to be false positive and due to
      131I uptake in a necklace that had been contaminated by the patient's saliva.
      This case stresses the importance of having the patient remove all jewelry before
      undergoing a radioiodine survey.

PMID- 15731021
TI  - Radiation dose to PET technologists and strategies to lower occupational
      exposure.
AB  - OBJECTIVE: The use of PET in Australia has grown rapidly. We conducted a
      prospective study of the radiation exposure of technologists working in PET and
      evaluated the occupational radiation dose after implementation of strategies to
      lower exposure. METHODS: Radiation doses measured by thermoluminescent dosimeters
      over a 2-y period were reviewed both for technologists working in PET and for
      technologists working in general nuclear medicine in a busy academic nuclear
      medicine department. The separate components of the procedures for dose
      administration and patient monitoring were assessed to identify the areas
      contributing the most to the dose received. The impact on dose of implementing
      portable 511-keV syringe shields (primary shields) and larger trolley-mounted
      shields (secondary shields) was also compared with initial results using no
      shield. RESULTS: We found that the radiation exposure of PET technologists was
      higher than that of technologists performing general nuclear medicine studies,
      with doses averaging 771 +/- 147 and 524 +/- 123 microSv per quarter,
      respectively (P = 0.01). The estimated dose per PET procedure was 4.1 microSv (11
      nSv/MBq). Injection of 18F-FDG contributed the most to radiation exposure. The
      511-keV syringe shield reduced the average dose per injection from 2.5 to 1.4
      microSv (P < 0.001). For the longer period of dose transportation and injection,
      the additional use of the secondary shield resulted in a significantly lower dose
      of radiation than did use of the primary shield alone or no shield (1.9 vs. 3.6
      microSv [P = 0.01] and 3.4 microSv [P = 0.03], respectively). CONCLUSION: The
      radiation doses currently received by technologists working in PET are within
      accepted occupational health guidelines, but improved shielding can further
      reduce the dose.

PMID- 15731022
TI  - Components of preparedness statements to accompany 2003 task analysis.
AB  - The Nuclear Medicine Technology Certification Board presents Components of
      Preparedness Statements (COPS) to accompany its recently revised task list. The
      COPS expand the tasks identified as important to the practice of nuclear medicine
      technology. These tasks are developed through an extensive process called a task
      analysis, which is reviewed in the article. The COPS represent the final step in
      this process. The COPS presented in this special report complement the task
      analysis published in 2003.

PMID- 15731023
TI  - Anti-inflammatory and antimicrobial roles of secretory leukocyte protease
      inhibitor.

PMID- 15731024
TI  - Vibrio parahaemolyticus disruption of epithelial cell tight junctions occurs
      independently of toxin production.
AB  - Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis
      worldwide. Virulence is commonly associated with the production of two toxins,
      thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH). Although the
      majority of clinical isolates produce TDH and/or TRH, clinical samples lacking
      toxin genes have been identified. In the present study, we investigated the
      effects of V. parahaemolyticus on transepithelial resistance (TER) and
      paracellular permeability in Caco-2 cultured epithelial cells. We found that V.
      parahaemolyticus profoundly disrupts epithelial barrier function in Caco-2 cells
      and that this disruption occurs independently of toxin production. Clinical
      isolates with different toxin genotypes all led to a significant decrease in TER,
      which was accompanied by an increased flux of fluorescent dextran across the Caco
      2 monolayer, and profound disruption of actin and the tight junction-associated
      proteins zonula occludin protein 1 and occludin. Purified TDH, even at
      concentrations eightfold higher than those produced by the bacteria, had no
      effect on either TER or paracellular permeability. We used lactate dehydrogenase
      release as a measure of cytotoxicity and found that this parameter did not
      correlate with the ability to disrupt tight junctions. As the effect on barrier
      function occurs independently of toxin production, we used PCR to determine the
      toxin genotypes of V. parahaemolyticus isolates obtained from both clinical and
      environmental sources, and we found that 5.6% of the clinical isolates were toxin
      negative. These data strongly indicate that the effect on tight junctions is not
      due to TDH and suggest that there are other virulence factors.

PMID- 15731025
TI  - Sialic Acid metabolism and systemic pasteurellosis.
AB  - Pasteurella multocida subsp. multocida is a commensal and opportunistic pathogen
      of food animals, wildlife, and pets and a zoonotic cause of human infection
      arising from contacts with these animals. Here, an investigation of multiple
      serotype A strains demonstrated the occurrence of membrane sialyltransferase.
      Although P. multocida lacks the genes for the two earliest steps in de novo
      sialic acid synthesis, adding sialic acid to the growth medium resulted in
      uptake, activation, and subsequent transfer of sialic acid to a membrane acceptor
      resembling lipooligosaccharide. Two candidate-activating enzymes with homology to
      Escherichia coli cytidine 5'-monophospho-N-acetylneuraminate synthetase were
      overproduced as histidine-tagged polypeptides. The synthetase encoded by pm0187
      was at least 37 times more active than the pm1710 gene product, suggesting pm0187
      encodes the primary sialic acid cytidylyltransferase in P. multocida. A sialate
      aldolase (pm1715) mutant unable to initiate dissimilation of internalized sialic
      acid was not attenuated in the CD-1 mouse model of systemic pasteurellosis,
      indicating that the nutritional function of sialate catabolism is not required
      for systemic disease. In contrast, the attenuation of a sialate uptake-deficient
      mutant supports the essential role in pathogenesis of a sialylation mechanism
      that is dependent on an environmental (host) supply of sialic acid. The combined
      results provide the first direct evidence of sialylation by a precursor
      scavenging mechanism in pasteurellae and of a potential tripartite ATP
      independent periplasmic sialate transporter in any species.

PMID- 15731026
TI  - The StcE protease contributes to intimate adherence of enterohemorrhagic
      Escherichia coli O157:H7 to host cells.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a diarrheal pathogen that
      causes attaching and effacing (A/E) lesions on intestinal epithelial cells.
      Strains of the O157 serogroup carry the large virulence plasmid pO157, which
      encodes the etp type II secretion system that secretes the genetically linked
      zinc metalloprotease StcE. The Ler regulator controls expression of many genes
      involved in A/E lesion formation, as well as StcE, suggesting StcE may be
      important at a similar time during colonization. Our laboratory has previously
      demonstrated that StcE cleaves C1-esterase inhibitor, a regulator of multiple
      inflammation pathways. Here we report two new substrates for StcE, mucin 7 and
      glycoprotein 340, and that purified StcE reduces the viscosity of human saliva.
      We tested the hypothesis that StcE contributes to intimate adherence of EHEC to
      host cells by cleavage of glycoproteins from the cell surface. The fluorescent
      actin stain (FAS) test was used to observe the intimate adherence represented by
      fluorescently stained bacteria colocalized with regions of bundled actin formed
      on HEp-2 cells. An E. coli O157:H7 strain with a stcE gene deletion was not
      affected in its ability to generally adhere to HEp-2 cells, but it did score
      threefold lower on the FAS test than wild-type or complemented strains. Addition
      of exogenous recombinant StcE increased intimate adherence of the mutant to wild
      type levels. Thus, StcE may help block host clearance of E. coli O157:H7 by
      destruction of some classes of glycoproteins, and it contributes to intimate
      adherence of E. coli O157:H7 to the HEp-2 cell surface.

PMID- 15731027
TI  - Relationship between surface accessibility for PpmA, PsaA, and PspA and antibody
      mediated immunity to systemic infection by Streptococcus pneumoniae.
AB  - Antibodies to capsular polysaccharide (PS) are protective against systemic
      infection by Streptococcus pneumoniae, but the large number of pneumococcal
      serogroups and the age-related immunogenicity of pure PS limit the utility of PS
      based vaccines. In contrast, cell wall-associated proteins from different
      capsular serotypes can be cross-reactive and immunogenic in all age groups.
      Therefore, we evaluated three pneumococcal proteins with respect to relative
      accessibility to antibody, in the context of intact pneumococci, and their
      ability to elicit protection against systemic infection by encapsulated S.
      pneumoniae. Sequences encoding pneumococcal surface adhesin A (PsaA), putative
      protease maturation protein A (PpmA), and the N-terminal region of pneumococcal
      surface protein A (PspA) from S. pneumoniae strain A66.1 were cloned and
      expressed in Escherichia coli. The presence of genes encoding PsaA, PpmA, and
      PspA in 11 clinical isolates was examined by PCR, and the expression of these
      proteins by each strain was examined by Western blotting with antisera raised to
      the respective recombinant proteins. We used flow cytometry to demonstrate that
      PspA was readily detectable on the surface of the pneumococcal strains analyzed,
      whereas PsaA and PpmA were not. Consistent with these observations, mice with
      passively or actively acquired antibodies to PspA or type 3 PS were equivalently
      protected from homologous systemic challenge with type 3 pneumococci, whereas
      mice with passively or actively acquired antibodies to PsaA or PpmA were not
      effectively protected. These experiments support the hypothesis that the extent
      of protection against systemic pneumococcal infection is influenced by target
      antigen accessibility to circulating host antibodies.

PMID- 15731028
TI  - Susceptibility of germfree phagocyte oxidase- and nitric oxide synthase 2
      deficient mice, defective in the production of reactive metabolites of both
      oxygen and nitrogen, to mucosal and systemic candidiasis of endogenous origin.
AB  - Mice deficient for phagocyte oxidase (Phox) and nitric oxide synthase 2 (NOS2)
      (gp91phox-/-/NOS2-/-), defective in the production of both reactive oxygen
      intermediates (ROI) and reactive nitrogen intermediates (RNI), were used to
      investigate the role of phagocytic cells during mucosal and systemic candidiasis
      of endogenous origin. The alimentary tracts of germfree mice were colonized with
      Candida albicans wild type or each of two hyphal signaling-defective mutants
      (efg1/efg1 and efg1/efg1 cph1/cph1). All Candida-colonized gp91phox-/-/NOS2-/-
      mice were moribund within 12 to 15 days after oral inoculation. C. albicans wild
      type and mutant strains colonized the alimentary tracts equally well and were
      able to translocate, most likely via Peyer's patches and mesenteric lymph nodes,
      to the internal organs and trigger the formation of abscesses; however, the wild
      type and mutant strains did not survive in the abscessed murine tissues.
      Surprisingly, there was no significant difference in the ability of peritoneal
      exudate cells from gp91phox-/-/NOS2-/-, NOS2-/-, gp91phox-/-, or immunocompetent
      C57BL/6 mice to kill C. albicans in vitro. This suggests that anti-Candida
      factors other than ROI and RNI can control the growth of C. albicans and that
      gp91phox-/-/NOS2-/- mice die due to the inability of the host to control its
      inflammatory response to Candida. Correspondingly, reverse transcription-PCR
      analysis showed increased expression of the cytokines gamma interferon, tumor
      necrosis factor alpha, and the chemokines MIP-2 and KC at the site of infection,
      while interleukin-15 expression remained relatively unchanged between germfree
      and infected tissues. These studies indicate that defects in ROI and RNI enabled
      C. albicans to translocate and disseminate to the internal organs, resulting in
      an uncontrolled immune response, severe pathology, and death; however, ROI and
      RNI were not required for the killing of phagocytized C. albicans, indicating
      that other anti-Candida factors either compensate or are sufficient for the
      killing of phagocytized Candida.

PMID- 15731029
TI  - Identification of vaccine candidate peptides in the NcSRS2 surface protein of
      Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon
      secreting T lymphocytes of infected holstein cattle.
AB  - Previously, our laboratory showed that Holstein cattle experimentally infected
      with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes
      (CTL) that lyse infected, autologous target cells through a perforin-granzyme
      pathway. To identify specific parasite antigens inducing bovine CTL and helper T
      lymphocyte responses for vaccine development against bovine neosporosis, the
      tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole
      tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced
      potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by
      proliferation and gamma interferon (IFN-gamma) secretion, while recombinant
      NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope
      bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the
      entire NcSRS2 sequence. Four experimentally infected cattle with six different
      major histocompatibility complex (MHC) class II haplotypes were the source of
      immune cells used to identify NcSRS2 peptides presented by Holstein MHC
      haplotypes. NcSRS2 peptides were mapped by using IFN-gamma secretion by rNcSRS2
      stimulated, short-term T-lymphocyte cell lines, IFN-gamma enzyme-linked
      immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr
      release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum
      infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected
      ex vivo in peripheral blood by IFN-gamma ELISPOT and in vitro by measuring T
      lymphocyte IFN-gamma production and cytotoxicity. An immunodominant region of
      NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from
      the four cattle. These findings support investigation of subunit N. caninum
      vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2
      peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied
      MHC genotypes.

PMID- 15731030
TI  - Mucosal adjuvant properties of mutant LT-IIa and LT-IIb enterotoxins that exhibit
      altered ganglioside-binding activities.
AB  - LT-IIa and LT-IIb, the type II heat-labile enterotoxins of Escherichia coli, are
      closely related in structure and function to cholera toxin and LT-I, the type I
      heat-labile enterotoxins of Vibrio cholerae and E. coli, respectively. Recent
      studies from our group demonstrated that LT-IIa and LT-IIb are potent systemic
      and mucosal adjuvants. To determine whether binding of LT-IIa and LT-IIb to their
      specific ganglioside receptors is essential for adjuvant activity, LT-IIa and LT
      IIb enterotoxins were compared with their respective single-point substitution
      mutants which have no detectable binding activity for their major ganglioside
      receptors [e.g., LT-IIa(T34I) and LT-IIb(T13I)]. Both mutant enterotoxins
      exhibited an extremely low capacity for intoxicating mouse Y1 adrenal cells and
      for inducing production of cyclic AMP in a macrophage cell line. BALB/c female
      mice were immunized by the intranasal route with the surface adhesin protein
      AgI/II of Streptococcus mutans alone or in combination with LT-IIa, LT-IIa(T34I),
      LT-IIb, or LT-IIb(T13I). Both LT-IIa and LT-IIb potentiated strong mucosal and
      systemic immune responses against AgI/II. Of the two mutant enterotoxins, only LT
      IIb(T13I) had the capacity to strongly potentiate mucosal anti-AgI/II and
      systemic anti-AgI/II antibody responses. Upon boosting with AgI/II, however, both
      LT-IIa(T34I) and LT-IIb(T13I) enhanced humoral memory responses to AgI/II. Flow
      cytometry demonstrated that LT-IIa(T34I) had no affinity for cervical lymph node
      lymphocytes. In contrast, LT-IIb(T13I) retained binding activity for T cells, B
      cells, and macrophages, indicating that this immunostimulatory mutant enterotoxin
      interacts with one or more unknown lymphoid cell receptors.

PMID- 15731031
TI  - Toll-like receptor 2 mediates cellular activation by the B subunits of type II
      heat-labile enterotoxins.
AB  - The type II heat-labile enterotoxins (LT-IIa and LT-IIb) of Escherichia coli have
      an AB5 subunit structure similar to that of cholera toxin (CT) and other type I
      enterotoxins, despite significant differences in the amino acid sequences of
      their B subunits and different ganglioside receptor specificities. LT-II
      holotoxins and their nontoxic B subunits display unique properties as
      immunological adjuvants distinct from those of CT and its B subunits. In contrast
      to type II holotoxins, the corresponding pentameric B subunits, LT-IIaB and LT
      IIbB, stimulated cytokine release in both human and mouse cells dependent upon
      Toll-like receptor 2 (TLR2). Induction of interleukin-1beta (IL-1beta), IL-6, IL
      8, or tumor necrosis factor alpha in human THP-1 cells by LT-IIaB or LT-IIbB was
      inhibited by anti-TLR2 but not by anti-TLR4 antibody. Furthermore, transient
      expression of TLR1 and TLR2 in human embryonic kidney 293 cells resulted in
      activation of a nuclear factor-kappaB-dependent luciferase gene in response to LT
      IIaB or LT-IIbB. Moreover, peritoneal macrophages from TLR2-deficient mice failed
      to respond to LT-IIaB or LT-IIbB, in contrast to wild-type or TLR4-deficient
      cells. These results demonstrate that besides their established binding to
      gangliosides, the B subunits of type II enterotoxins also interact with TLR2.
      Although a ganglioside-nonbinding mutant (T34I) of LT-IIaB effectively induced
      cytokine release, a phenotypically similar point mutation (T13I) in LT-IIbB
      abrogated cytokine induction, suggesting a variable requirement for gangliosides
      as coreceptors in TLR2 agonist activity. TLR2-dependent activation of mononuclear
      cells by type II enterotoxin B subunits appears to be a novel mechanism whereby
      these molecules may exert their immunomodulatory and adjuvant activities.

PMID- 15731032
TI  - CD4+ T cells and toll-like receptors recognize Salmonella antigens expressed in
      bacterial surface organelles.
AB  - A better understanding of immunity to infection is revealed from the
      characteristics of microbial ligands recognized by host immune responses. Murine
      infection with the intracellular bacterium Salmonella generates CD4+ T cells that
      specifically recognize Salmonella proteins expressed in bacterial surface
      organelles such as flagella and membrane vesicles. These natural Salmonella
      antigens are also ligands for Toll-like receptors (TLRs) or avidly associated
      with TLR ligands such as lipopolysaccharide (LPS). PhoP/PhoQ, a regulon
      controlling Salmonella virulence and remodeling of LPS to resist innate immunity,
      coordinately represses production of surface-exposed antigens recognized by CD4+
      T cells and TLRs. These data suggest that genetically coordinated surface
      modifications may provide a growth advantage for Salmonella in host tissues by
      limiting both innate and adaptive immune recognition.

PMID- 15731033
TI  - Altered gingipain maturation in vimA- and vimE-defective isogenic mutants of
      Porphyromonas gingivalis.
AB  - We have previously shown that gingipain activity in Porphyromonas gingivalis is
      modulated by the unique vimA and vimE genes. To determine if these genes had a
      similar phenotypic effect on protease maturation and activation, isogenic mutants
      defective in those genes were further characterized. Western blot analyses with
      antigingipain antibodies showed RgpA-, RgpB-, and Kgp-immunoreactive bands in
      membrane fractions as well as the culture supernatant of both P. gingivalis W83
      and FLL93, the vimE-defective mutant. In contrast, the membrane of P. gingivalis
      FLL92, the vimA-defective mutant, demonstrated immunoreactivity only with RgpB
      antibodies. With mass spectrometry or Western blots, full-length RgpA and RgpB
      were identified from extracellular fractions. In similar extracellular fractions
      from P. gingivalis FLL92 and FLL93, purified RgpB activated only arginine
      specific activity. In addition, the lipopolysaccharide profiles of the vimA and
      vimE mutants were truncated in comparison to that of W83. While glycosylated
      proteins were detected in the membrane and extracellular fractions from the vimA-
      and vimE-defective mutants, a monoclonal antibody (1B5) that reacts with specific
      sugar moieties of the P. gingivalis cell surface polysaccharide and membrane
      associated Rgp gingipain showed no immunoreactivity with these fractions. Taken
      together, these results indicate a possible defect in sugar biogenesis in both
      the vimA- and vimE-defective mutants. These modulating genes play a role in the
      secretion, processing, and/or anchorage of gingipains on the cell surface.

PMID- 15731034
TI  - Recombinant guinea pig tumor necrosis factor alpha stimulates the expression of
      interleukin-12 and the inhibition of Mycobacterium tuberculosis growth in
      macrophages.
AB  - Tumor necrosis factor alpha (TNF-alpha) plays an important role in the host
      immune response to infection with the intracellular pathogen Mycobacterium
      tuberculosis. It is essential for the formation of protective tuberculous
      granulomas and regulates the expression of other cytokines which contribute to a
      protective immune response. Interleukin-12 (IL-12) is known to promote a Th1
      response, which is essential for antimycobacterial resistance. Recombinant guinea
      pig TNF-alpha (rgpTNF-alpha) protein (17 kDa) was purified, and its bioactivity
      was confirmed by its cytotoxicity for L929 fibroblasts. High titers of polyclonal
      anti-gpTNF-alpha antibody were obtained by immunization of rabbits. Resident
      alveolar and peritoneal macrophages were isolated from guinea pigs and infected
      with either the H37Ra or H37Rv strain of M. tuberculosis. The mRNA levels for TNF
      alpha and IL-12 p40 were measured using real-time PCR. IL-12 p40 mRNA was up
      regulated in a dose-dependent manner by rgpTNF-alpha alone. In infected
      macrophages, a lower dose of rgpTNF-alpha intensified the mRNA levels of TNF
      alpha and IL-12 p40. However, higher doses of rgpTNF-alpha suppressed TNF-alpha
      and IL-12 p40 mRNA. The antimycobacterial activity of macrophages was assessed by
      metabolic labeling of M. tuberculosis with [3H]uracil. Resident alveolar and
      peritoneal macrophages treated with anti-gpTNF-alpha antibody to block endogenous
      TNF-alpha exhibited increased intracellular mycobacterial growth. These data
      suggest that the dose of TNF-alpha is crucial to the stimulation of optimal
      expression of protective cytokines and that TNF-alpha contributes to the control
      of mycobacterial replication to promote host resistance against M. tuberculosis.

PMID- 15731035
TI  - The fimYZ genes regulate Salmonella enterica Serovar Typhimurium invasion in
      addition to type 1 fimbrial expression and bacterial motility.
AB  - An important step in Salmonella enterica serovar Typhimurium virulence is the
      ability to invade the intestinal epithelium. The invasion process requires a
      large number of genes encoded on Salmonella pathogenicity island 1 (SPI-1) at
      centisome 63 as well as genes located in other positions throughout the
      chromosome. Expression of the invasive phenotype is tightly regulated by
      environmental cues that are processed by a complex regulatory scheme. A central
      player in the invasion regulatory pathway is the HilA protein, which is
      transcriptional activator belonging to the OmpR/ToxR family. A number of positive
      regulators (hilC, hilD, fis, sirA/barA, csrAB, phoBR, fadD, envZ/ompR, and fliZ)
      and negative regulators (hha, hilE, lon, ams, phoPc and pag) have been identified
      that are able to alter expression of hilA transcription. Recent work has found
      that hilA transcription requires the HilD protein for activation. Other work has
      emphasized the importance of HilE as a negative regulator of hilA. Overexpression
      of hilE superrepresses hilA transcription, as well as the invasive phenotype. Two
      hybrid experiments suggest that HilE exerts its regulatory influence on hilA
      through protein-protein interactions with HilD as the protein does not bind to
      the hilA promoter nor does it affect hilD transcription. As it seems likely that
      hilE plays an important role in translating environmental signals into invasion
      gene regulation, we have attempted to identify how the hilE gene itself is
      regulated. Our results indicate that the fimYZ genes, response regulatory
      proteins involved in type 1 fimbrial gene expression and recently implicated in
      motility gene regulation, are important activators of hilE expression. These
      findings indicate that invasion gene expression is coregulated with motility and
      adherence and provide experimental evidence that the expression of these
      virulence phenotypes is a subset of the overall regulation of bacterial
      physiology.

PMID- 15731036
TI  - Functional implication of the hydrolysis of platelet endothelial cell adhesion
      molecule 1 (CD31) by gingipains of Porphyromonas gingivalis for the pathology of
      periodontal disease.
AB  - Periodontitis is a response of highly vascularized tissues to the adjacent
      microflora of dental plaque. Progressive disease has been related to consortia of
      anaerobic bacteria, with the gram-negative organism Porphyromonas gingivalis
      particularly implicated. The gingipains, comprising a group of cysteine
      proteinases and associated hemagglutinin domains, are major virulence
      determinants of this organism. As vascular expression of leukocyte adhesion
      molecules is a critical determinant of tissue response to microbial challenge,
      the objective of this study was to determine the capacity of gingipains to
      modulate the expression and function of these receptors. Given the potential
      multifunctional role of platelet endothelial cell adhesion molecule 1 (PECAM-1)
      in the vasculature, the effect of gingipains on PECAM-1 expression by endothelial
      cells was examined. Activated gingipains preferentially down-regulated PECAM-1
      expression on endothelial cells compared with vascular cell adhesion molecule 1
      and endothelial-leukocyte adhesion molecule 1, but the reduction in PECAM-1
      expression was completely inhibited in the presence of the cysteine proteinase
      inhibitor TLCK (Nalpha-p-tosyl-l-lysine chloromethyl ketone). Endothelial
      monolayers treated with activated gingipains demonstrated progressive
      intercellular gap formation that correlated with reduced intercellular junctional
      PECAM-1 expression as determined by Western blotting and immunofluorescence
      microscopy. This was accompanied by enhanced transfer of both albumin and
      neutrophils across the monolayer. The results suggest that degradation of PECAM-1
      by gingipains contributes to increased vascular permeability and neutrophil flux
      at disease sites.

PMID- 15731037
TI  - Broad degradation of proapoptotic proteins with the conserved Bcl-2 homology
      domain 3 during infection with Chlamydia trachomatis.
AB  - Chlamydiae are obligate intracellular bacteria that can inhibit apoptosis of
      their host cell. As shown recently, this inhibition is in part explained by the
      proteolytic degradation of the proapoptotic Bcl-2 family members (BH3-only
      proteins) Bim, Puma, and Bad upon chlamydial infection. In this study, we further
      explore this antiapoptotic mechanism. In cells infected with a Chlamydia
      trachomatis L2 strain, Bim, Puma, and Bad were degraded with similar kinetics,
      and the degradation of all three was blocked by inhibition of the proteasome.
      Furthermore, the BH3-only proteins Bmf, Noxa, and tBid were also targeted by
      chlamydial infection. The constitutively expressed Bmf disappeared during
      infection. When Noxa was experimentally induced, the levels were also reduced by
      infection with C. trachomatis. In death-receptor-induced apoptosis, cleaved and
      activated tBid was degraded, and this destruction was also prevented by
      inhibition of the proteasome. These results show that chlamydial infection leads
      to a broad degradation of BH3-only proteins. This loss of proapoptotic factors
      can explain the almost general protection of infected cells against apoptotic
      stimuli.

PMID- 15731038
TI  - Role of the Pst system in plaque formation by the intracellular pathogen Shigella
      flexneri.
AB  - In response to the host cell environment, the intracellular pathogen Shigella
      flexneri induces the expression of numerous genes, including those in the pst
      operon which is predicted to encode a high-affinity phosphate acquisition system
      that is expressed under reduced phosphate conditions. An S. flexneri pst mutant
      forms smaller plaques in Henle cell monolayers than does the parental strain.
      This mutant exhibited normal production and localization of the S. flexneri IcsA
      protein. The pst mutant had the same growth rate as the parental strain in both
      phosphate-reduced and phosphate-replete media in vitro and during the first 3 h
      of growth in Henle cells in vivo. During growth in phosphate-replete media, the
      PhoB regulon was constitutively expressed in the pst mutant but not the parental
      strain. This suggested that the inability of the S. flexneri pst mutant to form
      wild-type plaques in Henle cell monolayers may be due to aberrant expression of
      the PhoB regulon. A mutation in phoB was constructed in the S. flexneri pst
      mutant, and the phoB mutation suppressed the small plaque phenotype of the pst
      mutant. Additionally, a specific mutation (R220Q) was constructed in the pstA
      gene of the pst operon that was predicted to eliminate Pst-mediated phosphate
      transport but allow normal PhoB-regulated gene expression, based on the phenotype
      of an Escherichia coli strain harboring the same mutation. Addition of this
      pstA(R220Q) mutation to a S. flexneri pst mutant, as part of the pst operon,
      restored normal plaque formation and regulation of phoA expression.

PMID- 15731039
TI  - A Vibrio vulnificus type IV pilin contributes to biofilm formation, adherence to
      epithelial cells, and virulence.
AB  - Vibrio vulnificus expresses a multitude of cell-associated and secreted factors
      that potentially contribute to pathogenicity, although the specific roles of most
      of these factors have been difficult to define. Previously we have shown that a
      mutation in pilD (originally designated vvpD), which encodes a type IV prepilin
      peptidase/N-methyltransferase, abolishes expression of surface pili, suggesting
      that they belong to the type IV class. In addition, a pilD mutant exhibits
      reduced adherence to HEp-2 cells, a block in secretion of several exoenzymes that
      follow the type II secretion pathway, and decreased virulence. In this study, we
      have cloned and characterized a V. vulnificus type IV pilin (PilA) that shares
      extensive homology to group A type IV pilins expressed by many pathogens,
      including Vibrio cholerae (PilA), Pseudomonas aeruginosa (PilA), and Aeromonas
      hydrophila (TapA). The V. vulnificus pilA gene is part of an operon and is
      clustered with three other pilus biogenesis genes, pilBCD. Inactivation of pilA
      reduces the ability of V. vulnificus to form biofilms and significantly decreases
      adherence to HEp-2 cells and virulence in iron dextran-treated mice. Southern
      blot analysis demonstrates the widespread presence of both pilA and pilD in
      clinical as well as environmental strains of V. vulnificus.

PMID- 15731040
TI  - Rat/MgrA, a regulator of autolysis, is a regulator of virulence genes in
      Staphylococcus aureus.
AB  - We have previously identified mgrA (rat) as a regulator of autolysis in
      Staphylococcus aureus. Besides its effect on autolytic activity, we recently
      found alterations in the expression of regulator and target virulence genes in
      the mgrA mutant. Northern analysis and transcription fusion assays showed that
      inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and
      upregulation of sarS and spa. Although both SarA and agr are activators of alpha
      hemolysin and a repressors of protein A synthesis, we found that the
      transcription of sarA was not affected in the mgrA mutant and vice versa,
      indicating that MgrA likely regulates hla and spa in a SarA-independent manner.
      Previously we have shown that SarT, a SarA homolog, is a repressor of hla and an
      activator of spa, presumably by activating SarS, however, analysis of the double
      sarT mgrA mutant for hla and spa transcription indicated that the mgrA-mediated
      effect is not mediated via sarT. Our results further demonstrated that the mgrA
      gene product regulates hla and spa expression in a dual fashion, with the first
      being agr dependent and the second agr independent. In the agr-independent
      pathway, MgrA binds directly to hla and the sarS promoter to modulate alpha
      hemolysin and protein A expression. Thus, our studies here have defined the
      nature of interaction of mgrA with other regulators such as agr, sarS, and sarT
      and its role in regulating hla and spa transcription within the virulence
      regulatory network of S. aureus.

PMID- 15731041
TI  - IpaD of Shigella flexneri is independently required for regulation of Ipa protein
      secretion and efficient insertion of IpaB and IpaC into host membranes.
AB  - Shigella flexneri causes human dysentery after invading the cells of the colonic
      epithelium. The best-studied effectors of Shigella entry into colonocytes are the
      invasion plasmid antigens IpaC and IpaB. These proteins are exported via a type
      III secretion system (TTSS) to form a pore in the host membrane that may allow
      the translocation of other effectors into the host cytoplasm. TTSS-mediated
      secretion of IpaD is also required for translocation pore formation, bacterial
      invasion, and virulence, but the mechanistic role of this protein is unclear.
      IpaD is also known to be involved in controlling Ipa protein secretion, but here
      it is shown that this activity can be separated from its requirement for cellular
      invasion. Amino acids 40 to 120 of IpaD are not essential for IpaD-dependent
      invasion; however, deletions in this region still lead to constitutive IpaB/IpaC
      secretion. Meanwhile, a central deletion causes only a partial loss of control of
      Ipa secretion but completely eliminates IpaD's invasion function, indicating that
      IpaD's role in invasion is not a direct outcome of its ability to control Ipa
      secretion. As shigellae expressing ipaD N-terminal deletion mutations have
      reduced contact-mediated hemolysis activity and are less efficient at introducing
      IpaB and IpaC into erythrocyte membranes, it is possible that IpaD is responsible
      for insertion of IpaB/IpaC pores into target cell membranes. While efficient
      insertion of IpaB/IpaC pores is needed for optimal invasion efficiency, it may be
      especially important for Ipa-dependent membrane disruption and thus for efficient
      vacuolar escape and intercellular spread.

PMID- 15731042
TI  - Citrobacter rodentium lifA/efa1 is essential for colonic colonization and crypt
      cell hyperplasia in vivo.
AB  - Previously, we have identified a large gene (lifA, for lymphocyte inhibitory
      factor A) in enteropathogenic Escherichia coli (EPEC) encoding a protein termed
      lymphostatin that suppresses cytokine expression in vitro. This protein also
      functions as an adhesion factor for enterohemorrhagic E. coli (EHEC) and Shiga
      toxin-producing E. coli and is alternatively known as efa1 (EHEC factor for
      adherence 1). The lifA/efa1 gene is also present in Citrobacter rodentium, an
      enteric pathogen that causes a disease termed transmissible murine colonic
      hyperplasia (TMCH), which induces colitis and massive crypt cell proliferation,
      in mice. To determine if lifA/efa1 is required for C. rodentium-induced colonic
      pathology in vivo, three in-frame mutations were generated, disrupting the
      glycosyltransferase (GlM12) and protease (PrMC31) motifs and a domain in between
      that does not encode any known activity (EID3). In contrast to infection with
      wild-type C. rodentium, that with any of the lifA/efa1 mutant strains did not
      induce weight loss or TMCH. Enteric infection with motif mutants GlM12 and PrM31
      resulted in significantly reduced colonization counts during the entire 20-day
      course of infection. In contrast, EID3 was indistinguishable from the wild type
      during the initial colonic colonization, but cleared rapidly after day 8 of the
      infection. The colonic epithelium of all infected mice displayed increased
      epithelial regeneration. However, significantly increased regeneration was
      observed by day 20 only in mice infected with the wild-type in comparison to
      those infected with lifA/efa1 mutant EID3. In summary, lifA/efa1 is a critical
      gene outside the locus for enterocyte effacement that regulates bacterial
      colonization, crypt cell proliferation, and epithelial cell regeneration.

PMID- 15731044
TI  - The locus of enterocyte effacement-encoded effector proteins all promote
      enterohemorrhagic Escherichia coli pathogenicity in infant rabbits.
AB  - The genes encoding the enterohemorrhagic Escherichia coli (EHEC) type III
      secretion system (TTSS) and five effector proteins secreted by the TTSS are
      located on the locus of enterocyte effacement (LEE) pathogenicity island.
      Deletion of tir, which encodes one of these effector proteins, results in a
      profound reduction (approximately 10,000-fold) in EHEC colonization of the infant
      rabbit intestine, but the in vivo phenotypes of other LEE genes are unknown.
      Here, we constructed in-frame deletions in escN, the putative ATPase component of
      the TTSS, and the genes encoding the four other LEE-encoded effector proteins,
      EspH, Map, EspF, and EspG, to investigate the contributions of the TTSS and the
      translocated effector proteins to EHEC pathogenicity in infant rabbits. We found
      that the TTSS is required for EHEC colonization and attaching and effacing (A/E)
      lesion formation in the rabbit intestine. Deletion of escN reduced EHEC recovery
      from the rabbit intestine by approximately 10,000-fold. Although EspH, Map, EspF,
      and EspG were not required for A/E lesion formation in the rabbit intestine or in
      HeLa cells, these effector proteins promote EHEC colonization. Colonization by
      the espH and espF mutants was reduced throughout the intestine. In contrast,
      colonization by the map and espG mutants was reduced only in the small intestine,
      indicating that Map and EspG have organ-specific effects. EspF appears to down
      regulate the host response to EHEC, since we observed increased accumulation of
      polymorphonuclear leukocytes in the colonic mucosa of rabbits infected with the
      EHEC espF mutant. Thus, all the known LEE-encoded effector proteins influence
      EHEC pathogenicity.

PMID- 15731043
TI  - Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion
      via toll-like receptor 2 signaling.
AB  - Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be
      efficacious for the treatment of inflammatory bowel diseases, the underlying
      mechanisms of action still remain elusive. The aim of the present study was to
      analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of
      peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3
      stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium
      (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA
      content, and caspase 3 expression were measured by flow cytometry to assess cell
      cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis
      modulators were determined by immunoblotting, and cytokine profiles were
      determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling
      and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins
      mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E.
      coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling.
      E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein
      expression, contributing to the reduction of T-cell proliferation. E. coli Nissle
      1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor
      necrosis factor alpha, and gamma interferon but increased IL-10 production in
      PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate
      that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2
      dependent. The differential reaction of circulating and tissue-bound T cells
      towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle
      1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the
      expansion of newly recruited T cells into the mucosa and limit intestinal
      inflammation, while already activated tissue-bound T cells may eliminate
      deleterious antigens in order to maintain immunological homeostasis.

PMID- 15731045
TI  - Efficacy of vaccination of calves against hemorrhagic septicemia with a live aroA
      derivative of Pasteurella multocida B:2 by two different routes of
      administration.
AB  - Two groups of four calves each were immunized either intramuscularly (i.m.
      vaccinated) or intranasally (i.n. vaccinated) at 2 and 6 weeks of age with ca.
      10(9) CFU of a derivative of P. multocida serotype B:2 strain 85020 containing a
      deletion in the aroA gene (strain JRMT12). Both groups of calves and three
      unvaccinated control calves were challenged subcutaneously at 8 weeks of age with
      ca. 10(7) CFU of the wild-type 85020 strain. The first and second vaccinations
      caused a significant pyrexia and increase in the mean demeanor score (P <0.05) in
      i.m. but not i.n. vaccinated calves. Serum agglutinating activity against whole
      cells of P. multocida strain 85020 and immunoglobulin G antibody concentrations
      increased after the second vaccination in i.m. but not in i.n. vaccinated
      animals, and this difference was statistically significant (P <0.05).
      Concentrations of serum amyloid A (SAA) increased significantly 3 h after both
      the primary (P <0.05) and booster (P <0.001) i.m. vaccinations, but not in i.n.
      vaccinated calves. All four i.m. vaccinated calves were solidly immune to
      challenge with wild-type P. multocida B:2. However, the mean rectal temperatures,
      demeanor scores, and serum SAA concentrations of i.n. vaccinated and control
      calves increased significantly (P <0.01). Three i.n. vaccinated and two control
      calves were killed for humane reasons within 14 h postchallenge, and postmortem
      examination revealed pathological lesions consistent with hemorrhagic septicemia.
      These data showed that the aroA mutant strain, given i.m. as two doses 4 weeks
      apart, acted as an effective live-attenuated vaccine strain to protect calves
      against challenge with the virulent parent strain.

PMID- 15731046
TI  - Natural killer cells and Helicobacter pylori infection: bacterial antigens and
      interleukin-12 act synergistically to induce gamma interferon production.
AB  - Helicobacter pylori is known to induce a local immune response, which is
      characterized by activation of lymphocytes and the production of IFN-gamma in the
      stomach mucosa. Since not only T cells, but also natural killer (NK) cells, are
      potent producers of gamma interferon (IFN-gamma), we investigated whether NK
      cells play a role in the immune response to H. pylori infection. Our results
      showed that NK cells were present in both the gastric and duodenal mucosae but
      that H. pylori infection did not affect the infiltration of NK cells into the
      gastrointestinal area. Furthermore, we could show that NK cells could be
      activated directly by H. pylori antigens, as H. pylori bacteria, as well as
      lysate from H. pylori, induced the secretion of IFN-gamma by NK cells. NK cells
      were also activated without direct contact when separated from the bacteria by an
      epithelial cell layer, indicating that the activation of NK cells by H. pylori
      can also occur in vivo, in the infected stomach mucosa. Moreover, the production
      of IFN-gamma by NK cells was greatly enhanced when a small amount of interleukin
      12 (IL-12) was added, and this synergistic effect was associated with increased
      expression of the IL-12 receptor beta2. It was further evident that bacterial
      lysate alone was sufficient to induce the activation of cytotoxicity-related
      molecules. In conclusion, we demonstrated that NK cells are present in the
      gastroduodenal mucosa of humans and that NK cells produce high levels of IFN
      gamma when stimulated with a combination of H. pylori antigen and IL-12. We
      propose that NK cells play an active role in the local immune response to H.
      pylori infection.

PMID- 15731047
TI  - Translocation and surface expression of lipidated serogroup B capsular
      Polysaccharide in Neisseria meningitidis.
AB  - The capsule of N. meningitidis serogroup B, (alpha2-->8)-linked polysialic acid
      and the capsules of other meningococcal serogroups and of other gram-negative
      bacterial pathogens are anchored in the outer membrane through a 1,2
      diacylglycerol moiety. Previous work on the meningococcal cps complex in
      Escherichia coli K-12 indicated that deletion of genes designated lipA and lipB
      caused intracellular accumulation of hyperelongated capsule polymers lacking the
      phospholipid substitution. To better understand the role of lip and lipB in
      capsule expression in a meningococcal background, the location, sequence, and
      relationship to related bacterial capsule genes were defined and specific
      mutations in lipA and lipB were generated in the serogroup B meningococcal strain
      NMB. The lipA and lipB genes are located on the 3' end of the ctr operon and are
      most likely transcribed independently. Inactivation of lipA, lipB, and both
      resulted in the same total levels of capsular polymer production as in the
      parental controls; however, these mutants were as sensitive as an unencapsulated
      mutant to killing by normal human serum. Immunogold electron microscopy and flow
      cytometric analyses revealed intracellular inclusions of capsular polymers in
      lipA, lipB, and lipA lipB mutants. Capsular polymers purified from lipA, lipB,
      and lipA lipB mutants were lipidated. The phospholipid anchor was shown by gas
      chromatography-mass spectroscopy analysis to be a phosphodiester-linked 1,2
      dipalmitoyl (C16:0) glycerol moiety and was identical in structure to that found
      on the wild-type meningococcal capsule polymers. Thus, lipA and lipB do not
      encode proteins responsible for diacylglycerophosphatidic acid substitution of
      the meningococcal capsule polymer; rather, they are required for proper
      translocation and surface expression of the lipidated polymer.

PMID- 15731048
TI  - Inactivation of membrane tumor necrosis factor alpha by gingipains from
      Porphyromonas gingivalis.
AB  - Gingipains are cysteine proteinases produced by Porphyromonas gingivalis, a major
      causative bacterium of adult periodontitis. They consist of arginine-specific
      (HRgpA and RgpB) and lysine-specific (Kgp) proteinases. Gingipains strongly
      affect the host defense system by degrading some cytokines, components of the
      complement system, and several immune cell receptors. In an in vitro model,
      gingipains were shown to degrade soluble tumor necrosis factor alpha (TNF-alpha).
      However, since membrane TNF-alpha shows strong biological activity, especially in
      local inflammatory lesions, it was worth investigating whether gingipains might
      also destroy membrane TNF-alpha and limit its biological activities. To avoid a
      possible influence of gingipains on ADAM17, the secretase of TNF-alpha, the
      majority of experiments were performed using ADAM17-/- fibroblasts stably
      transfected with cDNA of human pro-TNF-alpha (ADAM17-/- TNF+). Arginine-specific
      gingipains (Rgp's) strongly diminished the level of TNF-alpha on the cell surface
      as measured by flow cytometry, and this process was not accompanied by an
      increased concentration of soluble TNF-alpha in the culture medium. Degradation
      of membrane TNF-alpha by Rgp's correlated with a strong decrease in TNF-alpha
      mediated biological activities of ADAM17-/- TNF+ cells. First, the activation
      state of transcription factor NF-kappaB was suppressed; second, the cells were no
      longer able to induce apoptosis in HL-60 cells. Kgp was also able to cleave
      membrane TNF-alpha, but its effect was much weaker than that of Rgp's. Gingipains
      also limited the binding of native TNF-alpha to the target cells. Thus,
      gingipains are able not only to cleave soluble TNF-alpha but also to destroy the
      membrane form of the cytokine, which may additionally dysregulate the cytokine
      network.

PMID- 15731049
TI  - Effect of mutations in the human immunoglobulin A1 (IgA1) hinge on its
      susceptibility to cleavage by diverse bacterial IgA1 proteases.
AB  - Components of the human immunoglobulin A1 (IgA1) hinge governing sensitivity to
      cleavage by bacterial IgA1 proteases were investigated. Recombinant antibodies
      with distinct hinge mutations were constructed from a hybrid comprised of human
      IgA2 bearing half of the human IgA1 hinge region. This hybrid antibody and all
      the mutant antibodies derived from it were resistant to cleavage by the IgA1
      proteases from Streptococcus oralis and Streptococcus mitis biovar 1 strains but
      were cleaved to various degrees by those of Streptococcus pneumoniae, some
      Streptococcus sanguis strains, and the type 1 and 2 IgA1 proteases of Haemophilus
      influenzae, Neisseria meningitidis, and Neisseria gonorrhoeae. Remarkably, those
      proteases that cleave a Pro-Ser peptide bond in the wild-type IgA1 hinge were
      able to cleave mutant antibodies lacking a Pro-Ser peptide bond in the hinge, and
      those that cleave a Pro-Thr peptide bond in the wild-type IgA1 hinge were able to
      cleave mutant antibodies devoid of a Pro-Thr peptide bond in the hinge. Thus, the
      enzymes can cleave alternatives to their preferred postproline peptide bond when
      such a bond is unavailable. Peptide sequence analysis of a representative
      antibody digestion product confirmed this conclusion. The presence of a cleavable
      peptide bond near the CH2 end of the hinge appeared to result in greater cleavage
      than if the scissile bond was at the CH1 end of the hinge. Proline-to-serine
      substitution at residue 230 in a hinge containing potentially cleavable Pro-Ser
      and Pro-Thr peptide bonds increased the resistance of the antibody to cleavage by
      many IgA1 proteases.

PMID- 15731050
TI  - Helicobacter pylori induces interleukin-8 secretion by Toll-like receptor 2- and
      Toll-like receptor 5-dependent and -independent pathways.
AB  - Helicobacter pylori is an important human pathogen that causes gastritis and is
      strongly associated with gastric ulcers, gastric adenocarcinomas, and mucosa
      associated lymphoid tissue lymphomas. In response to H. pylori, interleukin-8 (IL
      8) is secreted from host cells to attract components of the innate and adaptive
      immune systems to the site of infection. Toll-like receptor 2 (TLR2) and TLR5
      have been shown to recognize H. pylori and to initiate signaling pathways that
      result in enhanced activation of NF-kappaB. Here, we evaluated the contribution
      of mitogen-activated protein kinase signaling pathways to TLR2-dependent and TLR5
      dependent secretion of IL-8. Secretion of IL-8 from H. pylori-infected HEK293
      cells was augmented by the expression of TLR2 or TLR5. While H. pylori infection
      resulted in the activation of ERK, JNK, and p38, the enhanced IL-8 secretion from
      TLR2- and TLR5-expressing cells coincided with increased p38 activation and
      phosphorylation of the transcription factor ATF2. When p38 activity was inhibited
      in TLR2- or TLR5-expressing cells, H. pylori-dependent IL-8 secretion returned to
      the level observed in infected parental HEK293 cells that did not express TLR2 or
      TLR5; inhibition of p38 had no effect on IL-8 secretion from infected parental
      HEK cells. In contrast, inhibition of JNK and/or ERK resulted in substantially
      less IL-8 secretion from infected cells, independent of TLR2 or TLR5 expression.
      Based on these data, we propose that H. pylori induces IL-8 secretion through a
      dual mechanism that includes a TLR2/5-independent component involving the
      activities of JNK and ERK and a TLR2/5-dependent component that requires p38
      activity.

PMID- 15731051
TI  - Antibody against V antigen prevents Yop-dependent growth of Yersinia pestis.
AB  - The V antigen (LcrV) of the plague bacterium Yersinia pestis is a potent
      protective antigen that is under development as a vaccine component for humans.
      LcrV is multifunctional. On the bacterial surface it mediates delivery of a set
      of toxins called Yops into host cells, and as a released protein it can cause
      production of the immunosuppressive cytokine interleukin-10 (IL-10) and can
      inhibit chemotaxis of polymorphonuclear neutrophils. It is not known how these
      mechanisms of LcrV operate, what their relative importance is, when they function
      during plague, and which are critical to protection by antibody. This study
      investigated several of these issues. C57BL/6 mice, mice unable to express IL-10,
      or mice with the macrophage lineage eliminated were treated with a protective
      anti-LcrV antibody or a nonprotective antibody against YopM and infected
      intravenously by Y. pestis KIM5 or a strain that lacked the genes encoding all
      six effector Yops. Viable bacterial numbers were determined at various times. The
      data indicated that Yops were necessary for Yersinia growth after the bacteria
      had seeded liver and spleen. Anti-LcrV antibody prevented this growth, even in IL
      10-/- mice, demonstrating that one protective mechanism for anti-LcrV antibody is
      independent of IL-10. Anti-LcrV antibody had no effect on persistence in organs
      of Y. pestis lacking effector Yops, even though the yersiniae could strongly
      express LcrV, suggesting that Yops are necessary for building sufficient
      bacterial numbers to produce enough LcrV for its immunosuppressive effects. In
      vitro assays showed that anti-LcrV antibody could partially block delivery of
      Yops and downstream effects of Yops in infected macrophage-like J774A.1 cells.
      However, cells of the macrophage lineage were found to be dispensable for
      protection by anti-LcrV antibody in spleen, although they contributed to
      protection in liver. Taken together, the data support the hypothesis that one
      protective effect of the antibody is to block delivery of Yops to host cells and
      prevent early bacterial growth. The findings also identified the macrophage
      lineage as one host cell type that mediates protection.

PMID- 15731052
TI  - Gingipains from Porphyromonas gingivalis W83 induce cell adhesion molecule
      cleavage and apoptosis in endothelial cells.
AB  - The presence of Porphyromonas gingivalis in the periodontal pocket and the high
      levels of gingipain activity detected in gingival crevicular fluid could
      implicate a role for gingipains in the destruction of the highly vascular
      periodontal tissue. To explore the effects of these proteases on endothelial
      cells, we exposed bovine coronary artery endothelial cells and human
      microvascular endothelial cells to gingipain-active extracellular protein
      preparations and/or purified gingipains from P. gingivalis. Treated cells
      exhibited a rapid loss of cell adhesion properties that was followed by apoptotic
      cell death. Cleavage of N- and VE-cadherin and integrin beta1 was observed in
      immunoblots of cell lysates. There was a direct correlation between the kinetics
      of cleavage of N- and VE-cadherin and loss of cell adhesion properties. Loss of
      cell adhesion, as well as N- and VE-cadherin and integrin beta1 cleavage, could
      be inhibited or significantly delayed by preincubation of P. gingivalis W83
      gingipain-active extracellular extracts with the cysteine protease inhibitor
      Nalpha-p-tosyl-l-lysine chloromethylketone. Furthermore, purified gingipains also
      induced endothelial cell detachment and apoptosis. Apoptosis-associated events,
      including annexin V positivity, caspase-3 activation, and cleavage of the caspase
      substrates poly(ADP-ribose) polymerase and topoisomerase I (Topo I), were
      observed in endothelial cells after detachment. All of the effects observed were
      correlated with the different levels of cysteine-dependent proteolytic activity
      of the extracts tested. Taken together, these results indicate that gingipains
      from P. gingivalis can alter cell adhesion molecules and induce endothelial cell
      death, which could have implications for the pathogenicity of this organism.

PMID- 15731053
TI  - Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on
      Toll-like receptor 2 and Dectin-1.
AB  - Coccidioides posadasii is a pathogenic fungus that causes endemic and epidemic
      coccidioidomycosis in the deserts of North, Central, and South America. How the
      innate immune system responds to the organism is not well understood. Here we
      show that elicited mouse peritoneal macrophages respond to spherules (the tissue
      form of the fungus) by producing proinflammatory cytokines as measured by
      quantitative PCR of cellular transcripts and by enzyme-linked immunosorbent assay
      (ELISA) assays for secreted protein. We examined the contribution of Toll-like
      receptors (TLR) and MyD88 in macrophage responses to formalin-killed spherules
      (FKS) by comparing cytokine responses of elicited macrophages from different
      knockout mice. FKS were added to elicited mouse peritoneal macrophages from wild
      type, TLR2-/-, and MyD88-/- cells, and wild-type cells made more tumor necrosis
      factor alpha, MIP-2, and interleukin 6 than did the mutant macrophages. In
      contrast, the C3H/HeJ mice, which have a point mutation in TLR4, and TLR4-/- B6
      mice exhibited no defect in cytokine production compared to the control mice. We
      also investigated the role of the macrophage beta-glucan receptor, Dectin-1. RAW
      264.7 macrophages overexpressing Dectin-1 produced more cytokines in respond to
      FKS, live spherules, and purified beta-glucan than did control RAW cells.
      Blockage of Dectin-1 with antibodies inhibited cytokine production in elicited
      mouse peritoneal macrophages. Taken together, these results show that cytokine
      responses in mouse peritoneal macrophages to C. posadasii spherules are dependent
      on TLR2, MyD88, and Dectin-1.

PMID- 15731054
TI  - Identification and characterization of an immunodominant 28-kilodalton Coxiella
      burnetii outer membrane protein specific to isolates associated with acute
      disease.
AB  - Coxiella burnetii causes acute Q fever in humans and occasional chronic
      infections that typically manifest as endocarditis or hepatitis. Isolates
      associated with acute disease were found to be distinct from a group of chronic
      disease isolates by a variety of biochemical parameters and in a guinea pig fever
      model of acute disease, suggesting a difference in virulence potential. We
      compared antigenic polypeptides among C. burnetii isolates and found an
      immunodominant 28-kDa protein in acute group isolates but not in chronic group
      isolates (T. Ho, A. Hotta, G. Q. Zhang, S. V. Nguyen, M. Ogawa, T. Yamaguchi, H.
      Fukushi, and K. Hirai, Microbiol. Immunol. 42:81-85, 1998). In order to clone the
      adaA gene, the N-terminal amino acid sequence of adaA was determined and a 59-bp
      fragment was amplified from Nine Mile phase I DNA by PCR. The putative gene
      fragment was used to screen a lambda ZAP II genomic DNA library, and an open
      reading frame expressing a 28-kDa immunoreactive protein was identified. Sequence
      analysis predicted a gene encoding an approximately 28-kDa mature protein with a
      typical signal sequence. The adaA (acute disease antigen A) gene was detected in
      acute group C. burnetii isolates but not identified in chronic group isolates by
      PCR and Southern blotting. A typical signal peptide was predicted in adaA, and
      specific antibody to adaA reacted with the purified membrane fraction of acute
      group isolates by Western blotting, suggesting that adaA is exposed on the outer
      surface of C. burnetii. adaA was overexpressed in pET23a as a fusion protein in
      Escherichia coli to develop anti-recombinant adaA (anti-radaA) specific antibody,
      which recognized a approximately 28-kDa band in acute group isolates but not in
      chronic group isolates. In addition, immunoblotting indicates that radaA reacted
      with sera derived from animals infected with acute group isolates but did not
      react with sera from animals infected with chronic group isolates. These results
      support the idea that an adaA gene-targeted PCR assay and an radaA antigen-based
      serodiagnostic test may be useful for differential diagnosis of acute and chronic
      Q fever.

PMID- 15731055
TI  - A live and inactivated Chlamydia trachomatis mouse pneumonitis strain induces the
      maturation of dendritic cells that are phenotypically and immunologically
      distinct.
AB  - The intracellular bacterial pathogen Chlamydia trachomatis is a major cause of
      sexually transmitted disease worldwide. While protective immunity does appear to
      develop following natural chlamydial infection in humans, early vaccine trials
      using heat-killed C. trachomatis resulted in limited and transient protection
      with possible enhanced disease during follow-up. Thus, immunity following natural
      infection with live chlamydia may differ from immune responses induced by
      immunization with inactivated chlamydia. To study this differing immunology, we
      used murine bone marrow-derived dendritic cells (DC) to examine DC maturation and
      immune effector function induced by live and UV-irradiated C. trachomatis
      elementary bodies (live EBs and UV-EB, respectively). DC exposed to live EBs
      acquired a mature DC morphology; expressed high levels of major
      histocompatibility complex (MHC) class II, CD80, CD86, CD40, and ICAM-1; produced
      elevated amounts of interleukin-12 and tumor necrosis factor alpha; and were
      efficiently recognized by Chlamydia-specific CD4+ T cells. In contrast, UV-EB
      pulsed DC expressed low levels of CD40 and CD86 but displayed high levels of MHC
      class II, ICAM-1, and CD80; secreted low levels of proinflammatory cytokines; and
      exhibited reduced recognition by Chlamydia-specific CD4+ T cells. Adoptive
      transfer of live EB-pulsed DC was more effective than that of UV-EB-pulsed DC at
      protecting mice against challenge with live C. trachomatis. The expression of DC
      maturation markers and immune protection induced by UV-EB could be significantly
      enhanced by costimulation of DC ex vivo with UV-EB and oligodeoxynucleotides
      containing cytosine phosphate guanosine; however, the level of protection was
      significantly less than that achieved by using DC pulsed ex vivo with viable EBs.
      Thus, exposure of DC to live EBs results in a mature DC phenotype which is able
      to promote protective immunity, while exposure to UV-EB generates a semimature DC
      phenotype with less protective potential. This result may explain in part the
      differences in protective immunity induced by natural infection and immunization
      with whole inactivated organisms and is relevant to rational chlamydia vaccine
      design strategies.

PMID- 15731057
TI  - Rapid loss of motility of Helicobacter pylori in the gastric lumen in vivo.
AB  - The human pathogen Helicobacter pylori has infected more than half of the world's
      population. Nevertheless, the first step of infection, the acute colonization of
      the gastric mucus, is poorly understood. For successful colonization, H. pylori
      must retain active motility in the gastric lumen until it reaches the safety of
      the mucus layer. To identify the factors determining the acute colonization, we
      inserted bacteria into the stomach of anesthetized Mongolian gerbils. We adjusted
      the gastric juice to defined pH values of between 2.0 and 6.0 by using an
      autotitrator. Despite the fact that Helicobacter spp. are known to survive low pH
      values for a certain time in vitro, the length of time that H. pylori persisted
      under the assay conditions within the gastric juice in vivo was remarkably
      shorter. In the anesthetized animal we found H. pylori to be irreversibly
      immotile in less than 1 min at lumen pH values of 2 and 3. At pH 4 motility was
      lost after 2 min. However, the period of motility increased to more than 15 min
      at pH 6. Blocking pepsins in the gastric lumen in vivo by using pepstatin
      significantly increased the period of motility. It was possible to simulate the
      rapid in vivo immotilization in vitro by adding pepsins. We conclude that pepsin
      limits the persistence of H. pylori in the gastric chymus to only a few minutes
      by rapidly inhibiting active motility. It is therefore likely that this short
      period of resistance in the gastric lumen is one of the most critical phases of
      Helicobacter infection.

PMID- 15731056
TI  - Staphylococcus aureus capsular polysaccharide types 5 and 8 reduce killing by
      bovine neutrophils in vitro.
AB  - Isogenic variants of Staphylococcus aureus strain Reynolds expressing either no
      capsule or capsular polysaccharide (CP) type 5 (CP5) or type 8 (CP8) were used to
      assess the effect of CP on bacterial killing and the respiratory burst of bovine
      neutrophils. The effects of antisera specific for CP5 and CP8 were also
      evaluated. The killing of live bacteria by isolated neutrophils was quantified in
      a bactericidal assay, while the respiratory burst after stimulation with live
      bacteria in whole blood was measured by flow cytometry. The expression of a CP5
      or CP8 capsule protected the bacteria from being killed by bovine neutrophils in
      vitro (P <0.001), and the capsule-expressing variants did not stimulate
      respiratory burst activity in calf whole blood. The addition of serotype-specific
      antisera increased the killing of the capsule-expressing bacteria and enhanced
      their stimulating effect in the respiratory burst assay (P <0.01). When the S.
      aureus variants were grown under conditions known not to promote capsule
      expression, there were no significant differences between them. The present study
      demonstrates that the expression of S. aureus CP5 or CP8 confers resistance to
      opsonophagocytic killing and prevents the bacteria from inducing respiratory
      burst of bovine neutrophils in vitro and that these effects can be reversed by
      the addition of serotype-specific antisera.

PMID- 15731059
TI  - Rapid method for the construction of Salmonella enterica Serovar Typhimurium
      vaccine carrier strains.
AB  - Salmonella enterica serovar Typhimurium is a versatile organism for the
      generation of live recombinant vaccines for mucosal immunization. Various
      strategies have been devised for the stable and efficient expression of
      heterologous antigens by attenuated S. enterica strains, but these methods often
      require complex manipulations. Use of phage lambda Red recombinase has recently
      been devised for gene replacements in Escherichia coli and S. enterica after
      introduction of PCR products. Based on this method, we have developed an approach
      that allows the integration of recombinant expression cassettes for heterologous
      antigens in a single step. The recombinant construct is integrated into the
      chromosome and is devoid of any selective marker such as antibiotic resistance.
      We observed the stable expression of model antigens without selective pressure.
      In addition, the method allows the simultaneous generation of attenuating
      mutations by gene deletions. The novel "knock-in" approach allows the rapid and
      efficient construction of recombinant Salmonella strains as vaccine carriers.

PMID- 15731058
TI  - Bordetella pertussis-infected human monocyte-derived dendritic cells undergo
      maturation and induce Th1 polarization and interleukin-23 expression.
AB  - Bordetella pertussis, the causative agent of whooping cough, is internalized by
      several cell types, including epithelial cells, monocytes, and neutrophils.
      Although its ability to survive intracellularly is still debated, it has been
      proven that cell-mediated immunity (CMI) plays a pivotal role in protection. In
      this study we aimed to clarify the interaction of B. pertussis with human
      monocyte-derived dendritic cells (MDDC), evaluating the ability of the bacterium
      to enter MDDC, to survive intracellularly, to interfere with the maturation
      process and functional activities, and to influence the host immune responses.
      The results obtained showed that B. pertussis had a low capability to be
      internalized by-and to survive in-MDDC. Upon contact with the bacteria, immature
      MDDC were induced to undergo phenotypic maturation and acquired antigen
      presenting-cell functions. Despite the high levels of interleukin-10 (IL-10) and
      the barely detectable levels of IL-12 induced by B. pertussis, the bacterium
      induced maturation of MDDC and T helper 1 (Th1) polarized effector cells. Gene
      expression analysis of the IL-12 cytokine family clearly demonstrated that B.
      pertussis induced high levels of the p40 and p19 subunits of IL-23 yet failed to
      induce the expression of the p35 subunit of IL-12. Overall our findings show that
      B. pertussis, even if it survives only briefly in MDDC, promotes the synthesis of
      IL-23, a newly discovered Th1 polarizing cytokine. A Th1-oriented immune response
      is thus allowed, relevant in the induction of an adequate CMI response, and
      typical of protection induced by natural infection or vaccination with whole-cell
      vaccines.

PMID- 15731060
TI  - Gelatinase is important for translocation of Enterococcus faecalis across
      polarized human enterocyte-like T84 cells.
AB  - Previously, in our laboratory, we established a two-chamber system to study
      translocation of Enterococcus faecalis across monolayers of polarized human colon
      carcinoma-derived T84 cells. By using the same system in the present study, we
      now show that disruption of gelE of strain OG1RF, which also has a polar effect
      on the cotranscribed sprE, as well as disruption of its regulatory system (fsrA,
      fsrB, and fsrC) resulted in a loss of detectable translocation by E. faecalis
      OG1RF; these mutants lost gelatinase (GelE) and serine protease (SprE) production
      by standard assay. A gelE deletion mutant of OG1RF (GelE- SprE+) also showed that
      significantly reduced translocation and complementation with the gelE gene
      (pTEX5438) in trans restored gelatinase and translocation, demonstrating that
      gelatinase is important for E. faecalis translocation. Complementation of fsrA,
      fsrB, and fsrC mutants with all three fsr genes also resulted in production of
      gelatinase and translocation. Furthermore, introduction of fsr genes into two non
      gelatinase-producing E. faecalis isolates, the well-characterized laboratory
      strain JH2-2 and a human-derived fecal isolate, TX1322 (both of which have gelE
      but not fsrA or fsrB, are gelatinase negative, and do not translocate), resulted
      in gelatinase production by these strains and restored translocation across T84
      monolayers, while transformation with pTEX5438 (gelE) showed little or no
      translocation and no detectable gelatinase, confirming the importance of both fsr
      and gelatinase for E. faecalis translocation. The importance of gelatinase
      production was also corroborated among 20 E. faecalis human isolates (7 fecal, 7
      endocarditis, and 6 urine isolates), which showed translocation by all gelatinase
      positive isolates but little to no translocation for gelatinase nonproducers.
      These results indicate that gelatinase is important for the successful in vitro
      translocation of E. faecalis across human enterocyte-like T84 cells.

PMID- 15731061
TI  - Transcriptional control of the rhuIR-bhuRSTUV heme acquisition locus in
      Bordetella avium.
AB  - Iron (Fe) is an essential nutrient for most bacterial pathogens. In these
      organisms, a variety of regulatory systems that respond to specific Fe complexes
      found within their vertebrate hosts have evolved. In Bordetella avium, the heme
      utilization locus encoded by rhuIR-bhuRSTUV mediates efficient acquisition of Fe
      from heme and hemoproteins. Control of bhuRSTUV expression is promulgated at two
      levels. When Fe is abundant, expression is repressed in a Fur-dependent manner
      which is partially relieved when Fe is limiting. In the presence of heme or
      hemoproteins, expression of the bhuRSTUV operon is induced via a three-component
      signal transduction cascade composed of RhuI, RhuR, and BhuR. Herein, we report
      the identification of two promoters (PrhuI and PbhuR) that control expression of
      the rhuIR-bhuRSTUV cluster. Primer extension analysis identified the
      transcriptional start site of PrhuI within a putative Fur box. Transcriptional
      initiation of PbhuR mapped within the rhuR-bhuR intergenic region. Maximal
      transcription from PbhuR required Fe-limiting conditions, the presence of heme
      (or hemoglobin), and rhuI; however, analysis of transcripts produced from the
      rhuIR-bhuRSTUV locus revealed a pattern of low-level bhuR transcription in the
      absence of heme which originated from both PbhuR and PrhuI. Transcription from
      PrhuI was repressed by Fe in the presence of fur and somewhat enhanced by the
      addition of hemin to Fe-limited media. The nature of this hemin-associated PrhuI
      stimulation was rhuI independent and therefore not induced by heme via the BhuR
      RhuR-RhuI signal cascade. Fe also repressed transcription from PbhuR in a fur
      dependent manner; however, activation from this promoter, in the presence or
      absence of heme, did not occur without rhuI.

PMID- 15731062
TI  - Monocytes are highly sensitive to clostridium difficile toxin A-induced apoptotic
      and nonapoptotic cell death.
AB  - In this study we investigated the in vitro responses of peripheral blood
      mononuclear preparations and purified monocytes to Clostridium difficile toxin A.
      In contrast to the responses of T and B cells, exposure to toxin A led to a rapid
      loss of monocytes in a time- and dose-dependent fashion (the majority of cells
      were lost within 24 h of exposure to >100 ng of toxin per ml). Transmission
      electron microscopy, flow cytometry, and fluorescence microscopy after propidium
      iodide and Hoechst staining showed that cell death in purified preparations of
      monocytes following exposure to 100 and 1,000 ng of toxin A per ml occurred by
      apoptosis. Further studies showed that 5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazole-carbocyanine iodide aggregates were retained within toxin
      A-exposed monocyte mitochondria, but cytochrome c was released, suggesting that
      the apoptotic cascade was triggered in the absence of mitochondrial permeability
      transition. There was also an increase in caspase-3 activity in toxin A
      stimulated monocytes. Following exposure to very high concentrations of toxin A
      (30 microg/ml), monocyte cell death was predominantly of the necrotic type, with
      rapid extracellular release of lactate dehydrogenase. These studies demonstrated
      that C. difficile toxin A has a cell-specific effect, in which monocytes exhibit
      greater susceptibility than lymphocytes and their death is induced in a
      concentration-dependent manner.

PMID- 15731063
TI  - Demonstration of Type IV pilus expression and a twitching phenotype by
      Haemophilus influenzae.
AB  - Haemophilus influenzae is considered a nonmotile organism that expresses neither
      flagella nor type IV pili, although H. influenzae strain Rd possesses a cryptic
      pilus locus. We demonstrate here that the homologous gene cluster pilABCD in an
      otitis media isolate of nontypeable H. influenzae strain 86-028NP encodes a
      surface appendage that is highly similar, structurally and functionally, to the
      well-characterized subgroup of bacterial pili known as type IV pili. This gene
      cluster includes a gene (pilA) that likely encodes the major subunit of the
      heretofore uncharacterized H. influenzae-expressed type IV pilus, a gene with
      homology to a type IV prepilin peptidase (pilD) as well as two additional
      uncharacterized genes (pilB and pilC). A second gene cluster (comABCDEF) was also
      identified by homology to other pil or type II secretion system genes. When grown
      in chemically defined medium at an alkaline pH, strain 86-028NP produces
      approximately 7-nm-diameter structures that are near polar in location.
      Importantly, these organisms exhibit twitching motility. A mutation in the pilA
      gene abolishes both expression of the pilus structure and the twitching
      phenotype, whereas a mutant lacking ComE, a Pseudomonas PilQ homologue, produced
      large appendages that appeared to be membrane bound and terminated in a slightly
      bulbous tip. These latter structures often showed a regular pattern of areas of
      constriction and expansion. The recognition that H. influenzae possesses a
      mechanism for twitching motility will likely profoundly influence our
      understanding of H. influenzae-induced diseases of the respiratory tract and
      their sequelae.

PMID- 15731064
TI  - Interactions of OspA monoclonal antibody C3.78 with Borrelia burgdorferi within
      ticks.
AB  - The Borrelia burgdorferi outer surface protein A (OspA) vaccine induces
      antibodies that prevent transmission from the tick to the host. Here we describe
      studies with an OspA monoclonal antibody (C3.78) to understand the mechanism by
      which antibodies entering the tick block Borrelia transmission. Host complement
      in the tick's blood meal did not contribute to protection because the antibody
      was equally effective whether infected ticks fed on normal or complement
      deficient mice. Antibody-mediated cross-linking of bacteria or cross-linking of
      OspA molecules was not required for protection because C3.78 Fab' fragments were
      as effective as whole antibody molecules. At low C3.78 concentrations,
      transmission was blocked despite the presence of many live spirochetes within the
      tick, confirming that clearance of Borrelia organisms was not required to block
      transmission. We propose that OspA antibody binding to the surface of spirochetes
      blocks transmission by a mechanism that does not require bacterial killing.

PMID- 15731065
TI  - The Pseudomonas aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L
      homoserine lactone inhibits T-cell differentiation and cytokine production by a
      mechanism involving an early step in T-cell activation.
AB  - The Pseudomonas aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L
      homoserine lactone (OdDHL) has been reported to have immunomodulatory activity in
      several systems, although the mechanism of that activity remains to be fully
      characterized. We demonstrate here, using a defined in vitro model of antigen
      responses by T-cell receptor (TCR)-transgenic mouse splenic CD4 T cells, that the
      effect of OdDHL on activation and cytokine production is complete within 4 h of
      antigen or mitogen stimulation and does not depend on the insertion of OdDHL in
      the cell membrane, despite a previous report that immunosuppression by homoserine
      lactones required a minimum acyl chain length of 11 carbons (S. R. Chhabra, C.
      Harty, D. S. W. Hooi, M. Daykin, B. W. Bycroft, P. Williams, and D. Pritchard, J.
      Med. Chem. 46:97-104, 2003). We also demonstrate that while OdDHL can have toxic
      effects on nonlymphoid leukocytes, it does not induce significant cell death in T
      cells at the concentrations (< or =10 microM) used in these experiments. In
      addition, we show that primary and secondary antigen-specific cytokine responses
      are equally susceptible to inhibition by OdDHL and that the compound inhibits the
      differentiation of both Th1 and Th2 cells. However, the precise balance of
      cytokine production by CD4 T cells stimulated in the presence of OdDHL varies
      with both the antigen concentration and its affinity for the transgenic TCR.
      Thus, conflicting reports of the nature of the immunosuppression by OdDHL may be
      due in part to the differences in antigen affinity and concentration in different
      models.

PMID- 15731066
TI  - Comparison between Candida albicans agglutinin-like sequence gene expression
      patterns in human clinical specimens and models of vaginal candidiasis.
AB  - Expression of the eight genes in the Candida albicans agglutinin-like sequence
      (ALS) family was studied by reverse transcription-PCR of RNA isolated from
      clinical vaginal fluid specimens and vaginal candidiasis model systems. Although
      expression of all ALS genes was detected across the set of clinical specimens,
      ALS1, ALS2, ALS3, and ALS9 transcripts were detected most frequently, and
      expression of ALS4 and ALS5 was detected least frequently. Laboratory strain
      3153A and two C. albicans strains isolated from the clinical specimens were
      studied using two models of vaginal candidiasis to determine how closely these
      models mimicked the clinical specimens at the level of gene expression. ALS gene
      expression patterns in a murine vaginitis model were identical to those from the
      clinical specimens. Expression of more ALS genes was detected in specimens
      collected 7 days after infection compared to those collected at 4 days. Similar
      patterns of ALS gene expression were observed when the three C. albicans strains
      were tested in the reconstituted human vaginal epithelium model. In this model,
      expression of ALS4, ALS5, ALS6, and ALS7 was least frequently detected. Negative
      or weakened signals for ALS4 expression were observed at early time points,
      suggesting that ALS4 expression, which was strong in the inoculum cells, was down
      regulated upon contact of C. albicans with vaginal epithelial cells in this
      model. The data presented here support the conclusion of host-site-specific
      influences on ALS gene expression and validate the use of the experimental models
      for evaluating the phenotype of als/als mutant strains.

PMID- 15731067
TI  - Gastric helicobacter infection induces a Th2 phenotype but does not elevate serum
      cholesterol in mice lacking inducible nitric oxide synthase.
AB  - Persistent Helicobacter felis infection in (C57BL/6 x 129SvEv)F1 mice induces
      chronic gastritis. Expression of inducible nitric oxide synthase (iNOS) is
      upregulated in response to Helicobacter infection. In this study, 20 10-week-old
      iNOS-/- mice and 20 wild-type [(C57BL/6 x 129SvEv)F1] mice were infected with H.
      felis by oral gavage and were assessed histologically and serologically at 32
      weeks postinfection. Equal numbers of uninfected controls were sham inoculated.
      The mice were scored for severity of gastric inflammation, hyperplasia, glandular
      atrophy, and mucous metaplasia in the corpus and for the level of helicobacter
      colonization. The immunoglobulin G1 (IgG1), IgG2a, and IgG2c antibody responses
      to H. felis were determined. As a secondary measure, serum cholesterol levels
      were assessed. iNOS-/- mice have a propensity for increased serum cholesterol,
      and although controversial, several human epidemiologic studies have demonstrated
      an association between Helicobacter infection and several risk factors for
      cardiovascular disease, including elevated serum cholesterol. Nevertheless, no
      differences in serum cholesterol levels were observed between the H. felis
      infected and -uninfected iNOS-/- mice in this study. The uninfected animals had
      minimal to no gastric pathology. The gastric pathology scores for the infected
      animals were reduced significantly in the iNOS-deficient mice relative to those
      for the wild-type mice (all P <0.01). Helicobacter-infected iNOS-/- mice had
      chronic lymphoid infiltration and negligible to mild glandular atrophy and mucous
      metaplasia in the fundic mucosa, while H. felis-infected wild-type mice had
      severe atrophic and metaplastic mucosal changes. The atrophic gastritis in the
      infected wild-type mice, particularly the female mice, was also accompanied by
      greater granulocytic infiltration, antral hyperplasia, and diminished antral
      colonization, unlike that in the infected iNOS-/- mice. iNOS-/- mice developed
      significantly lower Th1-associated IgG2c antibody responses to H. felis (P
      <0.0003); the Th2-associated IgG1 responses were similar (P=0.09), suggesting a
      greater effect of the iNOS defect on Th1 responses. H. felis colonization was
      significantly greater in the iNOS-deficient mice. These findings are indicative
      of an impaired Th1 component of the H. felis-induced inflammatory response when
      the influence of iNOS is removed.

PMID- 15731068
TI  - Characterization of a novel leucine-rich repeat protein antigen from group B
      streptococci that elicits protective immunity.
AB  - Group B streptococci (GBS) usually behave as commensal organisms that
      asymptomatically colonize the gastrointestinal and urogenital tracts of adults.
      However, GBS are also pathogens and the leading bacterial cause of life
      threatening invasive disease in neonates. While the events leading to
      transmission and disease in neonates remain unclear, GBS carriage and level of
      colonization in the mother have been shown to be significant risk factors
      associated with invasive infection. Surface antigens represent ideal vaccine
      targets for eliciting antibodies that can act as opsonins and/or inhibit
      colonization and invasion. Using a genetic screen for exported proteins in GBS,
      we identified a gene, designated lrrG, that encodes a novel LPXTG anchored
      surface antigen containing leucine-rich repeat (LRR) motifs found in bacterial
      invasins and other members of the LRR protein family. Southern blotting showed
      that lrrG was present in all GBS strains tested, representing the nine serotypes,
      and revealed the presence of an lrrG homologue in Streptococcus pyogenes.
      Recombinant LrrG protein was shown in vitro to adhere to epithelial cells in a
      dose-dependent manner, suggesting that it may function as an adhesion factor in
      GBS. More importantly, immunization with recombinant LrrG elicited a strong
      immunoglobulin G response in CBA/ca mice and protected against lethal challenge
      with virulent GBS. The data presented in this report suggest that this conserved
      protein is a highly promising candidate antigen for use in a GBS vaccine.

PMID- 15731069
TI  - HosA, a member of the SlyA family, regulates motility in enteropathogenic
      Escherichia coli.
AB  - In enteropathogenic and enterohemorraghic Escherichia coli (EPEC and EHEC), two
      members of the SlyA family of transcriptional regulators have been identified as
      SlyA. Western blot analysis of the wild type and the corresponding hosA and slyA
      deletion mutants indicated that SlyA and HosA are distinct proteins whose
      expression is not interdependent. Of 27 different E. coli strains (EPEC, EHEC,
      enteroinvasive, enteroaggregative, uropathogenic, and commensal) examined, 14
      were positive for both genes and proteins. To investigate hosA expression, a
      hosA::luxCDABE reporter gene fusion was constructed. hosA expression was
      significantly reduced in the hosA but not the slyA mutant and was influenced by
      temperature, salt, and pH. In contrast to SlyA, HosA did not activate the cryptic
      E. coli K-12 hemolysin ClyA. Mutation of hosA did not influence type III
      secretion, the regulation of the LEE1 and LEE4 operons, or the ability of
      E2348/69 to form attaching-and-effacing lesions on intestinal epithelial cells.
      HosA is, however, involved in the temperature-dependent positive control of
      motility on swim plates and regulates fliC expression and FliC protein levels. In
      electrophoretic mobility shift assays, purified HosA protein bound specifically
      to the fliC promoter, indicating that HosA directly modulates flagellin
      expression. While direct examination of flagellar structure and the motile
      behavior of individual hosA cells grown in broth culture at 30 degrees C did not
      reveal any obvious differences, hosA mutants, unlike the wild type, clumped
      together, forming nonmotile aggregates which could account for the markedly
      reduced motility of the hosA mutant on swim plates at 30 degrees C. We conclude
      that SlyA and HosA are independent transcriptional regulators that respond to
      different physicochemical cues to facilitate the environmental adaptation of E.
      coli.

PMID- 15731070
TI  - Activities of Pseudomonas aeruginosa effectors secreted by the Type III secretion
      system in vitro and during infection.
AB  - Pseudomonas aeruginosa utilizes a number of distinct pathways to secrete proteins
      that play various roles during infection. These include the type II secretion
      system, which is responsible for the secretion of the majority of exoproducts
      into the surrounding environment, including toxins and degradative enzymes. In
      contrast, the type III secretion system mediates the delivery of protein
      effectors directly into the cytoplasm of the host cell. Using tissue culture
      assays and a mouse acute-pneumonia model, we have determined the contribution of
      each of the type III effectors during infection. In strain PAK, ExoS is the major
      cytotoxin required for colonization and dissemination during infection. ExoT
      confers protection of tissue culture cells from type III-dependent lysis, while
      ExoY seemed to have little effect on cytotoxicity. ExoU is over 100-fold more
      cytotoxic than ExoS. The cytotoxicity of type II secretion was determined
      following deletion of the genes for the more toxic type III secretion system. The
      participation of these secretion systems during lifelong colonization of cystic
      fibrosis (CF) patients is unclear. By comparing clonal strains from the same
      patient isolated at the initial onset of P. aeruginosa infection and more than a
      decade later, after chronic colonization has been established, we show that
      initial strains are more cytotoxic than chronic strains that have evolved to
      reduce type III secretion. Constitutive expression of genes for the type III
      secretion system restored ExoS secretion but did not always reestablish
      cytotoxicity, suggesting that CF strains accumulate a number of mutations to
      reduce bacterial toxicity to the host.

PMID- 15731071
TI  - Role of the type III secreted exoenzymes S, T, and Y in systemic spread of
      Pseudomonas aeruginosa PAO1 in vivo.
AB  - Pseudomonas aeruginosa uses a dedicated type III secretion system to deliver
      toxins directly into the cytoplasm of host cells. While progress has been made in
      elucidating the function of type III-secreted toxins in vitro, the in vivo
      functions of the type III-secreted exoenzymes are less well understood,
      particularly for the sequenced strain PAO1. Therefore, we have systematically
      deleted the genes for the three known type III effector molecules (exoS, exoT,
      and exoY) in P. aeruginosa PAO1 and assayed the effect of the deletions, both
      singly and in combination, on cytotoxicity in vitro and in vivo. We found that
      the type III secretion system acts differently on different cell types, causing
      an exoST-dependent rounding of a lung epithelial-like cell line in contrast to
      causing an exoSTY-independent but translocase (popB)-dependent lysis of a
      macrophage cell line. We utilized an in vivo competitive infection model to test
      each of our mutants, examining replication in the lung and spread to secondary
      sites such as the blood and spleen. Type III mutants inoculated intranasally
      exhibited only a minor defect in replication and survival in the lung, but popB
      and exoSTY triple mutants were profoundly defective in their ability to spread
      systemically. Intravenous injection of the mutants indicated that the type III
      secretion machinery is required for survival in the blood. Furthermore, our
      findings suggest that the effector-independent popB-dependent cytotoxicity that
      we and others have observed in vitro in macrophage cell lines may not be of great
      importance in vivo.

PMID- 15731072
TI  - Salmonella enterica Serovar Typhimurium infection of dendritic cells leads to
      functionally increased expression of the macrophage-derived chemokine.
AB  - Gene expression in murine dendritic cells (DCs) infected with green fluorescent
      protein-expressing Salmonella enterica serovar Typhimurium BRD509 was studied by
      mRNA differential display. Infected DCs were sorted from uninfected cells by flow
      cytometry. The mRNA expression patterns of infected and uninfected cells revealed
      a number of differentially expressed transcripts, which included the macrophage
      derived chemokine (MDC). Up-regulation of MDC transcription in infected DCs was
      confirmed by Northern blotting, and the kinetics of MDC expression was examined
      by real-time reverse transcription-PCR, with which 31- and 150-fold increases
      were detected at 2 and 6 h postinfection, respectively. The increased release by
      DCs of MDC into culture media was detected by an enzyme-linked immunosorbent
      assay. The biological activity of MDC was investigated in in vitro and in vivo
      assays. In vitro, supernatants from S. enterica serovar Typhimurium-infected DCs
      were chemoattractive to T cells, and neutralization of MDC in these supernatants
      inhibited T-cell migration. Passive transfer of anti-MDC antibody to mice
      infected with BRD509 revealed that neither growth of the bacterium nor resistance
      of the mice to reinfection was affected and that in vivo inhibition of MDC did
      not affect T-cell responses, as measured by the gamma interferon ELISPOT method 3
      days after challenge infection.

PMID- 15731073
TI  - Age alterations in extent and severity of experimental intranasal infection with
      Chlamydophila pneumoniae in BALB/c mice.
AB  - The intracellular bacterium Chlamydophila ("Chlamydia") pneumoniae is a pathogen
      for several respiratory diseases and may be a factor in the pathogenesis of
      chronic diseases of aging including atherosclerosis and Alzheimer's disease. We
      assessed whether aging is coupled with increased burden of infection in BALB/c
      mice after intranasal infection by C. pneumoniae. Six- and twenty-month-old
      BALB/c mice were infected intranasally with 5 x 10(4) inclusion forming units
      (IFU) or 5 x 10(5) IFU of C. pneumoniae. Lung, brain, and heart tissue were
      analyzed for infectious C. pneumoniae and for Chlamydophila antigen by
      immunohistochemistry. At both doses, aging was associated with a decreased
      proportion of animals that cleared infection from the lung and greater burden of
      infectious organism within the lung. We observed dose-dependent spread to the
      heart/ascending aorta in animals infected with C. pneumoniae. In mice given 5 x
      10(4) IFU, spread to the heart by day 14 was only observed in old mice. By day
      28, all animals inoculated with 5 x 10(4) IFU showed evidence of spread to the
      heart, although higher C. pneumoniae titers were observed in the hearts from old
      mice. In mice inoculated with 5 x 10(5) IFU, spread of C. pneumoniae to the heart
      was evident by day 14, with no discernible age effect. C. pneumoniae was also
      recovered from the central nervous system (brain and olfactory bulb) of all mice
      by day 28 postinfection, with higher C. pneumoniae titers in old animals than in
      young animals. Our results suggest that infection with C. pneumoniae may be more
      severe in old animals.

PMID- 15731074
TI  - Identification of enterohemorrhagic Escherichia coli O26:H- genes required for
      intestinal colonization in calves.
AB  - Enterohemorrhagic Escherichia coli (EHEC) infections in humans are an important
      public health problem and are commonly acquired via contact with ruminant feces.
      The serogroups that are predominantly associated with human infection in the
      United States and Europe are O157 and O26. Serotypes O157:H7 and O26:H- differ in
      their virulence and tissue tropism in calves and therefore may colonize calves by
      distinct mechanisms. The mechanisms underlying EHEC intestinal colonization and
      pathogenesis are poorly understood. Signature-tagged mutagenesis was used to
      identify 59 genes of EHEC O26:H- that are required for the intestinal
      colonization of calves. Our results indicate important roles for locus of
      enterocyte effacement (LEE)-encoded type III secreted proteins in intestinal
      colonization. In addition, colonization is facilitated by cytotoxins, putative
      type III secreted proteins unlinked to the LEE, a putative fimbrial operon, and
      numerous genes involved in central metabolism and transport and genes of unknown
      function. Our data also imply that the elaboration of type I fimbriae by EHEC
      O26:H- is disadvantageous for persistence within the bovine intestines. These
      observations have important implications for the design of vaccines to control
      these important zoonotic pathogens.

PMID- 15731075
TI  - Neutrophil responses to Mycobacterium tuberculosis infection in genetically
      susceptible and resistant mice.
AB  - The role of neutrophils in tuberculosis (TB) resistance and pathology is poorly
      understood. Neutrophil reactions are meant to target the offending pathogen but
      may lead to destruction of the host lung tissue, making the defending cells an
      enemy. Here, we show that mice of the I/St strain which are genetically
      susceptible to TB show an unusually high and prolonged neutrophil accumulation in
      their lungs after intratracheal infection. Compared to neutrophils from more
      resistant A/Sn mice, I/St neutrophils display an increased mobility and tissue
      influx, prolonged lifespan, low expression of the CD95 (Fas) apoptotic receptor,
      relative resistance to apoptosis, and an increased phagocytic capacity for
      mycobacteria. Segregation genetic analysis in (I/St x A/Sn)F2 hybrids indicates
      that the alleles of I/St origin at the chromosome 3 and 17 quantitative trait
      loci which are involved in the control of TB severity also determine a high level
      of neutrophil influx. These features, along with the poor ability of neutrophils
      to restrict mycobacterial growth compared to that of lung macrophages, indicate
      that the prevalence of neutrophils in TB inflammation contributes to the
      development of pathology, rather than protection of the host, and that
      neutrophils may play the role of a "Trojan horse" for mycobacteria.

PMID- 15731076
TI  - Distinct roles of pattern recognition receptors CD14 and Toll-like receptor 4 in
      acute lung injury.
AB  - Acute lung injury (ALI) induced by lipopolysaccharide (LPS) is a major cause of
      mortality among humans. ALI is characterized by microvascular protein leakage,
      neutrophil influx, and expression of proinflammatory mediators, followed by
      severe lung damage. LPS binding to its receptors is the crucial step in the
      causation of these multistep events. LPS binding and signaling involves CD14 and
      Toll-like receptor 4 (TLR4). However, the relative contributions of CD14 and TLR4
      in the induction of ALI and their therapeutic potentials are not clear in vivo.
      Therefore, the aim of the present study was to compare the roles of CD14 and TLR4
      in LPS-induced ALI to determine which of these molecules is the more critical
      target for attenuating ALI in a mouse model. Our results show that CD14 and TLR4
      are necessary for low-dose (300-microg/ml) LPS-induced microvascular leakage, NF
      kappaB activation, neutrophil influx, cytokine and chemokine (KC, macrophage
      inflammatory protein 2, tumor necrosis factor alpha, interleukin-6) expression,
      and subsequent lung damage. On the other hand, when a 10-fold-higher dose of LPS
      (3 mg/ml) was used, these responses were only partially dependent on CD14 and
      they were totally dependent on TLR4. The CD14-independent LPS response was
      dependent on CD11b. A TLR4 blocking antibody abolished microvascular leakage,
      neutrophil accumulation, cytokine responses, and lung pathology with a low dose
      of LPS but only attenuated the responses with a high dose of LPS. These data are
      the first to demonstrate that LPS-induced CD14-dependent and -independent (CD11b
      dependent) signaling pathways in the lung are entirely dependent on TLR4 and that
      blocking TLR4 might be beneficial in lung diseases caused by LPS from gram
      negative pathogens.

PMID- 15731077
TI  - Plasmodium falciparum Malaria: reduction of endothelial cell apoptosis in vitro.
AB  - Organ failure in Plasmodium falciparum malaria is associated with neutrophil
      activation and endothelial damage. This study investigates whether neutrophil
      induced endothelial damage involves apoptosis and whether it can be prevented by
      neutralization of neutrophil secretory products. Endothelial cells from human
      umbilical veins were coincubated with neutrophils from healthy donors and with
      sera from eight patients with P. falciparum malaria, three patients with P. vivax
      malaria, and three healthy controls. Endothelial apoptosis was demonstrated by
      terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling
      (TUNEL) and annexin V staining. The rate of apoptosis of cells was markedly
      increased after incubation with patient serum compared to that with control
      serum. Apoptosis was most pronounced after incubation with sera from two patients
      with fatal cases of P. falciparum malaria, followed by sera of survivors with
      severe P. falciparum malaria and, finally, by sera of patients with mild P.
      falciparum and P. vivax malaria. Ascorbic acid, tocopherol, and ulinastatin
      reduced the apoptosis rate, but gabexate mesilate and pentoxifylline did not.
      Furthermore, in fatal P. falciparum malaria, apoptotic endothelial cells were
      identified in renal and pulmonary tissue by TUNEL staining. These findings show
      that apoptosis caused by neutrophil secretory products plays a major role in
      endothelial cell damage in malaria. The antioxidants ascorbic acid and tocopherol
      and the protease inhibitor ulinastatin can reduce malaria-associated endothelial
      apoptosis in vitro.

PMID- 15731078
TI  - Roles of cell adhesion and cytoskeleton activity in Entamoeba histolytica
      pathogenesis: a delicate balance.
AB  - The protozoan parasite Entamoeba histolytica colonizes the human large bowel.
      Invasion of the intestinal epithelium causes amoebic colitis and opens the route
      for amoebic liver abscesses. The parasite relies on its dynamic actomyosin
      cytoskeleton and on surface adhesion molecules for dissemination in the human
      tissues. Here we show that the galactose/N-acetylgalactosamine (Gal/GalNAc)
      lectin clusters in focal structures localized in the region of E. histolytica
      that contacts monolayers of enterocytes. Disruption of myosin II activity impairs
      the formation of these structures and renders the trophozoites avirulent for
      liver abscess development. Production of the cytoplasmic domain of the E.
      histolytica Gal/GalNAc lectin in engineered trophozoites causes reduced adhesion
      to enterocytes. Intraportal delivery of these parasites to the liver leads to the
      formation of a large number of small abscesses with disorganized morphology that
      are localized in the vicinity of blood vessels. The data support a model for
      invasion in which parasite motility is essential for establishment of infectious
      foci, while the adhesion to host cells modulates the distribution of trophozoites
      in the liver and their capacity to migrate in the hepatic tissue.

PMID- 15731079
TI  - Phenotypic switching of Cryptococcus neoformans can produce variants that elicit
      increased intracranial pressure in a rat model of cryptococcal
      meningoencephalitis.
AB  - Increased intracranial pressure (ICP) plays an important role in the morbidity
      and mortality of cryptococcal meningoencephalitis. The microbial and host factors
      that contribute to the development of increased ICP are poorly understood. We
      found that phenotypic switch variants of Cryptococcus neoformans (smooth and
      mucoid) differed in their abilities to promote increased ICP in a rat model of
      cryptococcal meningitis. Rats infected with the mucoid variant developed
      increased ICP, whereas rats infected with the smooth parent did not. This trend
      correlated with a shorter survival time and a higher cerebrospinal fluid (CSF)
      fungal burden for mucoid variant-infected rats, although brain fungal burdens
      were comparable between mucoid variant- and smooth parent-infected rats. Magnetic
      resonance imaging revealed enhanced T2 signal intensity over the surfaces of the
      brains of mucoid variant-infected rats. In addition, more polysaccharide
      accumulated in the CSF and brains of mucoid variant-infected rats. The
      accumulation of glucorunoxylomannan was associated with elevated levels of MCP-1
      (CCL2) and, accordingly, a more pronounced but ineffective monocytic inflammatory
      response in the meninges of mucoid variant-infected rats. In summary, these
      findings suggest that strain-specific characteristics can influence the
      development of increased ICP and indicate a manner in which phenotypic switching
      could influence the outcome of a central nervous system infection.

PMID- 15731080
TI  - The gamma interferon receptor is required for the protective pulmonary
      inflammatory response to Cryptococcus neoformans.
AB  - Mice with a null deletion mutation in the gamma interferon (IFN-gamma) receptor
      gene were used to study the role of IFN-gamma responsiveness during experimental
      pulmonary cryptococcosis. Cryptococcus neoformans was inoculated intratracheally
      into mice lacking the IFN-gamma receptor gene (IFN-gammaR-/-) and into control
      mice (IFN-gammaR+/+). The numbers of CFU in lung, spleen, and brain were
      determined to assess clearance; cytokines produced by lung leukocytes were
      measured, and survival curves were generated. In the present study, we
      demonstrate the following points. (i) IFN-gammaR-/- mice are markedly more
      susceptible to C. neoformans infection than IFN-gammaR+/+ mice. (ii) In the
      absence of IFN-gamma signaling, pulmonary CFU continue to increase over the
      course of infection, and the infection disseminates to the brain. (iii) In the
      absence of IFN-gamma receptor, recruitment of inflammatory cells in response to
      pulmonary cryptococcal infection is not impaired. (iv) At week 5 postinfection,
      IFN-gammaR-/- mice have recruited greater numbers of leukocytes into their lungs,
      with neutrophils, eosinophils, and lymphocytes accounting for this cellular
      increase. (v) IFN-gamma signaling is required for the development of a T1 over a
      T2 immune response in the lung following cryptococcal infection. These results
      indicate that in the absence of IFN- gamma responsiveness, even though the
      recruitment of pulmonary inflammatory cells is not impaired and the secretion of
      IFN-gamma is not affected, IFN-gammaR-/- mice do not have the ability to resolve
      the cryptococcal infection. In conclusion, our data suggest that proper
      functional IFN-gamma signaling, possibly through a mechanism which inhibits the
      potentially disease-promoting T2 response, is required for mice to confine the
      cryptococcal infection.

PMID- 15731081
TI  - Use of genome-wide expression profiling and mutagenesis to study the intestinal
      lifestyle of Campylobacter jejuni.
AB  - Campylobacter jejuni is the most common bacterial cause of diarrhea worldwide. To
      colonize the gut and cause infection, C. jejuni must successfully compete with
      endogenous microbes for nutrients, resist host defenses, persist in the
      intestine, and ultimately infect the host. These challenges require the
      expression of a battery of colonization and virulence determinants. In this
      study, the intestinal lifestyle of C. jejuni was studied using whole-genome
      microarray, mutagenesis, and a rabbit ileal loop model. Genes associated with a
      wide range of metabolic, morphological, and pathological processes were expressed
      in vivo. The in vivo transcriptome of C. jejuni reflected its oxygen-limited,
      nutrient-poor, and hyperosmotic environment. Strikingly, the expression of
      several C. jejuni genes was found to be highly variable between individual
      rabbits. In particular, differential gene expression suggested that C. jejuni
      extensively remodels its envelope in vivo by differentially expressing its
      membrane proteins and by modifying its peptidoglycan and glycosylation
      composition. Furthermore, mutational analysis of seven genes, hspR, hrcA, spoT,
      Cj0571, Cj0178, Cj0341, and fliD, revealed an important role for the stringent
      and heat shock response in gut colonization. Overall, this study provides new
      insights on the mechanisms of gut colonization, as well as possible strategies
      employed by Campylobacter to resist or evade the host immune responses.

PMID- 15731082
TI  - Biofilm formation, icaADBC transcription, and polysaccharide intercellular
      adhesin synthesis by staphylococci in a device-related infection model.
AB  - Biofilm formation of Staphylococcus epidermidis and S. aureus is mediated by the
      polysaccharide intercellular adhesin (PIA) encoded by the ica operon. We used a
      device-related animal model to investigate biofilm formation, PIA expression
      (immunofluorescence), and ica transcription (quantitative transcript analysis)
      throughout the course of infection by using two prototypic S. aureus strains and
      one S. epidermidis strain as well as corresponding ica mutants. During infection,
      the ica mutants were growth attenuated when inoculated in competition with the
      corresponding wild-type strains but not when grown singly. A typical biofilm was
      observed at the late course of infection. Only in S. aureus RN6390, not in S.
      aureus Newman, were PIA and ica-specific transcripts detectable after anaerobic
      growth in vitro. However, both S. aureus strains were PIA positive in vivo by day
      8 of infection. ica transcription preceded PIA expression and biofilm formation
      in vivo. In S. epidermidis, both PIA and ica expression levels were elevated
      compared to those in the S. aureus strains in vitro as well as in vivo and were
      detectable throughout the course of infection. In conclusion, in S. aureus, PIA
      expression is dependent on the genetic background of the strain as well as on
      strong inducing conditions, such as those dominating in vivo. In S. epidermidis,
      PIA expression is elevated and less vulnerable to environmental conditions.

PMID- 15731083
TI  - Colonization and inflammation deficiencies in Mongolian gerbils infected by
      Helicobacter pylori chemotaxis mutants.
AB  - Helicobacter pylori causes disease in the human stomach and in mouse and gerbil
      stomach models. Previous results have shown that motility is critical for H.
      pylori to colonize mice, gerbils, and other animal models. The role of
      chemotaxis, however, in colonization and disease is less well understood. Two
      genes in the H. pylori chemotaxis pathway, cheY and tlpB, which encode the
      chemotaxis response regulator and a methyl-accepting chemoreceptor, respectively,
      were disrupted. The cheY mutation was complemented with a wild-type copy of cheY
      inserted into the chromosomal rdxA gene. The cheY mutant lost chemotaxis but
      retained motility, while all other strains were motile and chemotactic in vitro.
      These strains were inoculated into gerbils either alone or in combination with
      the wild-type strain, and colonization and inflammation were assessed. While the
      cheY mutant completely failed to colonize gerbil stomachs, the tlpB mutant
      colonized at levels similar to those of the wild type. With the tlpB mutant,
      there was a substantial decrease in inflammation in the gerbil stomach compared
      to that with the wild type. Furthermore, there were differences in the numbers of
      each immune cell in the tlpB-mutant-infected stomach: the ratio of lymphocytes to
      neutrophils was about 8 to 1 in the wild type but only about 1 to 1 in the
      mutant. These results suggest that the TlpB chemoreceptor plays an important role
      in the inflammatory response while the CheY chemotaxis regulator plays a critical
      role in initial colonization. Chemotaxis mutants may provide new insights into
      the steps involved in H. pylori pathogenesis.

PMID- 15731084
TI  - Profile of Candida albicans-secreted aspartic proteinase elicited during vaginal
      infection.
AB  - Vaginal infections caused by the opportunistic yeast Candida albicans are a
      significant problem in women of child-bearing age. Several factors are recognized
      as playing a crucial role in the pathogenesis of superficial candidiasis; these
      factors include hyphal formation, phenotypic switching, and the expression of
      virulence factors, including a 10-member family of secreted aspartic proteinases.
      In the present investigation, we analyzed the secreted aspartic proteinase gene
      (SAP) expression profile of C. albicans that is elicited in the course of vaginal
      infection in mice and how this in vivo expression profile is associated with
      hyphal formation. We utilized two different genetic reporter systems that allowed
      us to observe SAP expression on a single-cell basis, a recombination-based in
      vivo expression technology and green fluorescent protein-expressing Candida
      reporter strains. Of the six SAP genes that were analyzed (SAP1 to SAP6), only
      SAP4 and SAP5 were detectably induced during infection in this model. Expression
      of both of these genes was associated with hyphal growth, although not all hyphal
      cells detectably expressed SAP4 and SAP5. SAP5 expression was induced soon after
      infection, whereas SAP4 was expressed at later times and in fewer cells compared
      with SAP5. These findings point to a link between morphogenetic development and
      expression of virulence genes during Candida vaginitis in mice, where host
      signals induce both hyphal formation and expression of SAP4 and SAP5, but
      temporal gene expression patterns are ultimately controlled by other factors.

PMID- 15731085
TI  - Role for flagella but not intimin in the persistent infection of the
      gastrointestinal tissues of specific-pathogen-free chicks by shiga toxin-negative
      Escherichia coli O157:H7.
AB  - Shiga toxin (Stx)-positive Escherichia coli O157:H7 readily colonize and persist
      in specific-pathogen-free (SPF) chicks, and we have shown that an Stx-negative E.
      coli O157:H7 isolate (NCTC12900) readily colonizes SPF chicks for up to 169 days
      after oral inoculation at 1 day of age. However, the role of intimin in the
      persistent colonization of poultry remains unclear. Thus, to investigate the role
      of intimin and flagella, which is a known factor in the persistence of non-O157
      E. coli in poultry, isogenic single- and double-intimin and aflagellar mutants
      were constructed in E. coli O157:H7 isolate NCTC12900. These mutants were used to
      inoculate (10(5) CFU) 1-day-old SPF chicks. In general, significant attenuation
      of the aflagellate and intimin-aflagellate mutants, but not the intimin mutant,
      was noted at similar time points between 22 and 92 days after inoculation. The
      intimin-deficient mutant was still being shed at the end of the experiment, which
      was 211 days after inoculation, 84 days more than the wild type. Shedding of the
      aflagellar and intimin-aflagellar mutants ceased 99 and 113 days after
      inoculation, respectively. Histological analysis of gastrointestinal tissues from
      inoculated birds gave no evidence for true microcolony formation by NCTC12900 or
      intimin and aflagellar mutants to epithelial cells. However, NCTC12900 mutant
      derivatives associated with the mucosa were observed as individual cells and/or
      as large aggregates. Association with luminal contents was also noted. These data
      suggest that O157 organisms do not require intimin for the persistent
      colonization of chickens, whereas flagella do play a role in this process.

PMID- 15731086
TI  - Bacterial and host factors implicated in nasal carriage of methicillin-resistant
      Staphylococcus aureus in mice.
AB  - Nasal carriage is a major risk factor for Staphylococcus aureus infection,
      especially for methicillin-resistant strains (MRSA). Using a mouse model of nasal
      carriage, we have compared several S. aureus strains and demonstrated increased
      colonization levels by MRSA in cystic fibrosis transmembrane conductance
      regulator-deficient mice and Toll-like receptor 2 (TLR2)-deficient mice but not
      TLR4-deficient mice.

PMID- 15731087
TI  - Use of green fluorescent protein and reverse transcription-PCR to monitor Candida
      albicans agglutinin-like sequence gene expression in a murine model of
      disseminated candidiasis.
AB  - Candida albicans PALS-green fluorescent protein (GFP) reporter strains were
      inoculated into mice in a disseminated candidiasis model, and GFP production was
      monitored by immunohistochemistry and reverse transcription-PCR (RT-PCR). GFP
      production from the ALS1 and ALS3 promoters was detected immunohistochemically.
      ALS1, ALS2, ALS3, ALS4, and ALS9 transcription was detected by RT-PCR, further
      identifying ALS genes expressed in this model.

PMID- 15731088
TI  - Factors characterizing Staphylococcus epidermidis invasiveness determined by
      comparative genomics.
AB  - Virulence mechanisms of the leading nosocomial pathogen Staphylococcus
      epidermidis are poorly understood. We used microarray-based genome-wide
      comparison of clinical and commensal S. epidermidis strains to identify putative
      virulence determinants. Our study revealed high genetic variability of the S.
      epidermidis genome, new markers for invasiveness of S. epidermidis, and potential
      targets for drug development against S. epidermidis infections.

PMID- 15731089
TI  - Degradation of the proapoptotic proteins Bik, Puma, and Bim with Bcl-2 domain 3
      homology in Chlamydia trachomatis-infected cells.
AB  - We have previously correlated Chlamydia trachomatis antiapoptotic activity with
      the blockade of mitochondrial cytochrome c release and the inhibition of Bax and
      Bak activation. We now report that C. trachomatis infection leads to degradation
      of Bik, Puma, and Bim, three upstream proapoptotic BH3-only proteins of the Bcl-2
      family that can transmit death signals to mitochondria by inhibiting the Bcl-2
      antiapoptotic proteins and/or activating the Bcl-2 proapoptotic members, such as
      Bax and Bak. This observation has provided new information on the chlamydial
      antiapoptosis mechanisms.

PMID- 15731090
TI  - Escherichia coli O157:H7 does not require intimin to persist in pigs.

PMID- 15731091
TI  - Production of a proteolytically active protein, chlamydial protease/proteasome
      like activity factor, by five different Chlamydia species.
AB  - We have previously identified a chlamydial protein, chlamydial
      protease/proteasome-like activity factor (CPAF), for degrading host transcription
      factors in cells infected with the human chlamydial species Chlamydia trachomatis
      or Chlamydia pneumoniae. We now report that functional CPAF was also produced
      during infection with the species Chlamydia muridarum, Chlamydia psittaci, and
      Chlamydia caviae, which primarily infect nonhuman hosts.

PMID- 15731092
TI  - Sublethal infection of C57BL/6 mice with Salmonella enterica Serovar Typhimurium
      leads to an increase in levels of Toll-like receptor 1 (TLR1), TLR2, and TLR9
      mRNA as well as a decrease in levels of TLR6 mRNA in infected organs.
AB  - Sublethal infection of C57BL/6 mice with Salmonella enterica serovar Typhimurium
      M525P initiates a strong inflammatory response. We measured organ expression of
      mRNA for Toll-like receptors and their associated signaling molecules during S.
      enterica serovar Typhimurium infection. During infection, the Toll-lie receptor 1
      (TLR1), TLR2, and TLR9 mRNA levels increased, while TLR6 mRNA expression
      decreased.

PMID- 15731094
TI  - Glutathione and nitrosoglutathione in macrophage defense against Mycobacterium
      tuberculosis.
AB  - We demonstrate that Mycobacterium tuberculosis grown in vitro is sensitive to
      glutathione and its derivative S-nitrosoglutathione. Furthermore, our infection
      studies with J774.1 macrophages indicate that glutathione is essential for the
      control of the intracellular growth of M. tuberculosis. This study indicates the
      important role of glutathione in the control of macrophages by M. tuberculosis.

PMID- 15731093
TI  - GeneChip analyses of global transcriptional responses of murine macrophages to
      the lethal toxin of Bacillus anthracis.
AB  - We performed GeneChip analyses on RNA from Bacillus anthracis lethal toxin (LeTx)
      treated RAW 264.7 murine macrophages to investigate global effects of anthrax
      toxin on host cell gene expression. Stringent analysis of data revealed that the
      expression of several mitogen-activated protein kinase kinase-regulatory genes
      was affected within 1.5 h post-exposure to LeTx. By 3.0 h, the expression of 103
      genes was altered, including those involved in intracellular signaling, energy
      production, and protein metabolism.

PMID- 15731095
TI  - Both CD1d antigen presentation and interleukin-12 are required to activate
      natural killer T cells during Trypanosoma cruzi infection.
AB  - Mechanisms of natural killer T (NKT)-cell activation remain unclear. Here, we
      report that during Trypanosoma cruzi infection, interleukin-12 (IL-12) deficiency
      or anti-CD1d antibody treatment prevents normal activation. The required IL-12
      arises independently of MyD88. The data support a model of normal NKT-cell
      activation that requires IL-12 and TCR stimulation.

PMID- 15731096
TI  - Genetic vaccination against murine cysticercosis by using a plasmid vector
      carrying Taenia solium paramyosin.
AB  - A plasmid vector carrying the immunoprotective amino-terminal fragment of Taenia
      solium paramyosin (VW2-1) was designed for genetic vaccination studies. Mice that
      were genetically immunized with VW2-1 and challenged by intraperitoneal
      inoculation of Taenia crassiceps cysticerci showed 43 to 48% reductions in the
      parasite burden, values which were similar to values obtained previously when the
      recombinant protein was used.

PMID- 15731097
TI  - Mycobacterium tuberculosis with disruption in genes encoding the phosphate
      binding proteins PstS1 and PstS2 is deficient in phosphate uptake and
      demonstrates reduced in vivo virulence.
AB  - By measuring phosphate uptake by Mycobacterium tuberculosis strains with the
      pstS1 and pstS2 genes genetically inactivated, we showed that these pstS genes
      encode high-affinity phosphate binding proteins. In a mouse infection model, both
      mutants were attenuated in virulence, suggesting that M. tuberculosis encounters
      limiting phosphate concentrations during its intracellular life span.

PMID- 15731098
TI  - Mice fed lipid-encapsulated Mycobacterium bovis BCG are protected against aerosol
      challenge with Mycobacterium tuberculosis.
AB  - Mice that consumed a single dose of 10(7) lipid-encapsulated Mycobacterium bovis
      BCG bacilli showed significant pulmonary and systemic protection against aerosol
      challenge with M. tuberculosis H37Rv. As an extension of previous challenge
      studies with virulent strains of M. bovis, this report describes a reduction in
      M. tuberculosis infection in mice vaccinated orally with lipid-encapsulated BCG
      comparable to that observed in mice vaccinated subcutaneously with BCG. These
      results are consistent with the induction of tuberculin-specific cell-mediated
      immune responses.

PMID- 15731099
TI  - Light-independent phosphorylation of WHITE COLLAR-1 regulates its function in the
      Neurospora circadian negative feedback loop.
AB  - Phosphorylation is a major regulatory mechanism controlling circadian clocks. In
      the Neurospora circadian clock, the PER-ARNT-SIM (PAS) domain-containing
      transcription factor, WHITE COLLAR (WC)-1, acts both as the blue light
      photoreceptor of the clock and as a positive element in the circadian negative
      feedback loop in constant darkness, by activating the transcription of the
      frequency (frq) gene. To understand the role of WC-1 phosphorylation, five in
      vivo WC-1 phosphorylation sites, located immediately downstream of the WC-1 zinc
      finger DNA binding domain, were identified by tandem mass spectrometry using
      biochemically purified endogenous WC-1 protein. Mutations of these
      phosphorylation sites suggest that they are major WC-1 phosphorylation sites
      under constant conditions but are not responsible for the light-induced
      hyperphosphorylation of WC-1. Although phosphorylation of these sites does not
      affect the light function of WC-1, strains carrying mutations of these sites show
      short period, low amplitude, or arrhythmic conidiation rhythms in constant
      darkness. Furthermore, normal or slightly higher levels of frq mRNA and FRQ
      proteins were observed in a mutant strain containing mutations of all five sites
      despite its low WC-1 levels. Together, these data suggest that phosphorylation of
      these sites negatively regulates the function of WC-1 in the circadian negative
      feedback loop and is important for the function of the Neurospora circadian
      clock.

PMID- 15731100
TI  - Syndecan-4 is required for thrombin-induced migration and proliferation in human
      vascular smooth muscle cells.
AB  - Thrombin is a mitogen and chemoattractant for vascular smooth muscle cells (SMCs)
      and may contribute to vascular lesion formation. We have previously shown that
      human SMCs, when stimulated with thrombin, release basic fibroblast growth factor
      (bFGF), causing phosphorylation of FGF receptor-1 (FGFR-1). Treatment with bFGF
      neutralizing antibodies (anti-bFGF) or heparin inhibits thrombin-induced DNA
      synthesis. We concluded that thrombin may stimulate entry into the cell cycle via
      bFGF release and FGFR-1 activation. In the present study, we demonstrate a
      requirement for not only FGFR-1 but also syndecan-4, a transmembrane heparan
      sulfate proteoglycan. Inhibition of syndecan-4 expression using small interfering
      RNA (siRNA) resulted in reduced DNA synthesis by human SMCs after stimulation
      with thrombin (10 nmol/liter). Anti-bFGF antibody, which inhibits DNA synthesis
      in control cells, had no inhibitory effect when syndecan-4 expression was reduced
      by siRNA. Thrombin- or bFGF-induced SMC migration, determined in Boyden chamber
      assays, was reduced in cells treated with syndecan-4 or FGFR-1 siRNA or by anti
      bFGF. Thrombin induced phosphorylation of extracellular signal-regulated kinase
      (ERK) 1/2 in a biphasic pattern. Although thrombin-mediated ERK phosphorylation
      at 5 min was not affected by syndecan-4 or FGFR-1 siRNA, ERK phosphorylation at
      later time points was reduced. We conclude that thrombin-released bFGF binds to
      syndecan-4 and FGFR-1, which is required for thrombin-induced mitogenesis and
      migration.

PMID- 15731102
TI  - A HIV-1 minimal gag protein is superior to nucleocapsid at in vitro annealing and
      exhibits multimerization-induced inhibition of reverse transcription.
AB  - HIV-1 uses tRNA3Lys to prime reverse transcription of its viral RNA. In this
      process, the 3'-end of tRNA3Lys must be annealed to the primer binding site of
      HIV-1 genomic RNA, and the two molecules together form a complex structure.
      During annealing, the nucleocapsid (NC) protein enhances the unwinding of
      tertiary structures within both RNA molecules. Moreover, the packaging of
      tRNA3Lys occurs prior to viral budding at a time when NC is still part of the
      Pr55Gag polyprotein. In contrast, Pr55Gag is able to produce virus-like particles
      on its own. We have recently shown that an N-terminal extended form of NC (mGag),
      containing all of the minimal elements required for virus-like particle
      formation, possesses greater affinity for HIV-1 genomic RNA than does NC alone.
      We have now studied the tRNA3Lys-annealing properties of mGag in comparison to
      those of NC and report that the former is more efficient in this regard than the
      latter. We have also tested each of a mutant version of mGag, an extended form of
      mGag, and an almost full-length form of Gag, and showed that all of these
      possessed greater tRNA-annealing capacity than did the viral NC protein. Yet,
      surprisingly, multimerization of Gag-related proteins did not abrogate this
      annealing process but rather resulted in dramatically reduced levels of reverse
      transcriptase processivity. These results suggest that the initial stages of
      reverse transcription may be regulated by the multimerization of Pr55Gag
      polyprotein at times prior to the cleavage of NC.

PMID- 15731101
TI  - Crystal structure of N-acetylornithine transcarbamylase from Xanthomonas
      campestris: a novel enzyme in a new arginine biosynthetic pathway found in
      several eubacteria.
AB  - We have identified in Xanthomonas campestris a novel N-acetylornithine
      transcarbamylase that replaces ornithine transcarbamylase in the canonic arginine
      biosynthetic pathway of several Eubacteria. The crystal structures of the protein
      in the presence and absence of the reaction product, N-acetylcitrulline, were
      determined. This new family of transcarbamylases lacks the DxxSMG motif that is
      characteristic of all ornithine transcarbamylases (OTCases) and contains a novel
      proline-rich loop that forms part of the active site. The specificity for N
      acetylornithine is conferred by hydrogen bonding with residues in the proline
      rich loop via water molecules and by hydrophobic interactions with residues from
      the adjacent 80's, 120's, and proline-rich loops. This novel protein structure
      provides a starting point for rational design of specific analogs that may be
      useful in combating human and plant pathogens that utilize acetylornithine
      transcarbamylase rather than ornithine transcarbamylase.

PMID- 15731103
TI  - Mechanistic differences in promoter DNA melting by Thermus aquaticus and
      Escherichia coli RNA polymerases.
AB  - Formation of strand-separated, functional complexes at promoters was compared for
      RNA polymerases from the mesophile Escherichia coli and the thermophile Thermus
      aquaticus. The RNA polymerases contained sigma factors that were wild type or
      bearing homologous alanine substitutions for two aromatic amino acids involved in
      DNA melting. Substitutions in the sigmaA subunit of T. aquaticus RNA polymerase
      impair promoter DNA melting equally at temperatures from 25 to 75 degrees C.
      However, homologous substitutions in sigma70 render E. coli RNA polymerase
      progressively more melting-defective as the temperature is reduced below 37
      degrees C. The effects of the mutations on the mechanism of promoter DNA melting
      were investigated by studying the interaction of wild type and mutant RNA
      polymerases with "partial promoters" mimicking promoter DNA where the nucleation
      of DNA melting had taken place. Because T. aquaticus and E. coli RNA polymerases
      bound these templates similarly, it was concluded that the different effects of
      the mutations on the two polymerases are exerted at a step preceding nucleation
      of DNA melting. A model is presented for how this mechanistic difference between
      the two RNA polymerase could explain our observations.

PMID- 15731104
TI  - Mitochondrial initiation factor 2 of Trypanosoma brucei binds imported formylated
      elongator-type tRNA(Met).
AB  - The mitochondrion of Trypanosoma brucei lacks tRNA genes. Its translation system
      therefore depends on the import of nucleus-encoded tRNAs. Thus, except for the
      cytosol-specific initiator tRNA(Met), all trypanosomal tRNAs function in both the
      cytosol and the mitochondrion. The only tRNA(Met) present in T. brucei
      mitochondria is therefore the one which, in the cytosol, is involved in
      translation elongation. Mitochondrial translation initiation depends on an
      initiator tRNA(Met) carrying a formylated methionine. This tRNA is then
      recognized by initiation factor 2, which brings it to the ribosome. To guarantee
      mitochondrial translation initiation, T. brucei has an unusual methionyl-tRNA
      formyltransferase that formylates elongator tRNA(Met). In the present study, we
      have identified initiation factor 2 of T. brucei and shown that its carboxyl
      terminal domain specifically binds formylated trypanosomal elongator tRNA(Met).
      Furthermore, the protein also recognizes the structurally very different
      Escherichia coli initiator tRNA(Met), suggesting that the main determinant
      recognized is the formylated methionine. In vivo studies using stable RNA
      interference cell lines showed that knock-down of initiation factor 2, depending
      on which construct was used, causes slow growth or even growth arrest. Moreover,
      concomitantly with ablation of the protein, a loss of oxidative phosphorylation
      was observed. Finally, although ablation of the methionyl-tRNA formyltransferase
      on its own did not impair growth, a complete growth arrest was observed when it
      was combined with the initiation factor 2 RNA interference cell line showing the
      slow growth phenotype. Thus, these experiments illustrate the importance of
      mitochondrial translation initiation for growth of procyclic T. brucei.

PMID- 15731105
TI  - Two purified domains of telomerase reverse transcriptase reconstitute sequence
      specific interactions with RNA.
AB  - Telomerase reverse transcriptase (TERT) and telomerase RNA (TER) function
      together to create a uniquely specialized polymerase. Here we have described for
      the first time domains of bacterially expressed Tetrahymena TERT that interacted
      directly with TER in the absence of assembly chaperones. We used quantitative
      binding assays to define TER sequence requirements for recognition by the high
      affinity RNA binding domain and an independent N-terminal RNA interaction domain.
      The TERT RNA binding domain and N-terminal RNA interaction domain had distinct,
      nonoverlapping requirements for TER sequence and structure that together
      accounted for all of the sites of TER contact inferred for full-length TERT. The
      TER residues important for TERT binding are only a subset of the residues
      required for catalytic activity. Our findings demonstrate telomerase functional
      specialization by an elaborate ribonucleoprotein architecture physically
      separable from the active site.

PMID- 15731106
TI  - HSP25 inhibits protein kinase C delta-mediated cell death through direct
      interaction.
AB  - Heat shock protein 25 (HSP25) interferes negatively with apoptosis through
      several pathways that involve its direct interaction with cytochrome c or Akt.
      Here we show that HSP25 inhibits protein kinase C (PKC) delta-mediated cell death
      through direct interaction. HSP25 binds to kinase-active PKCdelta to inhibit its
      kinase activity and translocation to the membrane, which results in reduced cell
      death. Deletion constructs of HSP25 and PKCdelta identified amino acids 90-103 of
      HSP25 and the C-terminal V5 region of PKCdelta as binding sites. In addition, the
      interaction between HSP25 and PKCdelta induced HSP25 phosphorylation at Ser-15
      and Ser-86, and these phosphorylations permitted HSP25 release from PKCdelta.
      Based on these observations, we propose that after PKCdelta activation, HSP25
      binds to the exposed V5 region of PKCdelta. This novel function of HSP25 accounts
      for its cytoprotective properties via the inhibition of PKCdelta and the
      enhancement of HSP25 phosphorylation.

PMID- 15731107
TI  - A structural basis for 14-3-3sigma functional specificity.
AB  - The 14-3-3 family of proteins includes seven isotypes in mammalian cells that
      play numerous diverse roles in intracellular signaling. Most 14-3-3 proteins form
      homodimers and mixed heterodimers between different isotypes, with overlapping
      roles in ligand binding. In contrast, one mammalian isoform, 14-3-3sigma,
      expressed primarily in epithelial cells, appears to play a unique role in the
      cellular response to DNA damage and in human oncogenesis. The biological and
      structural basis for these 14-3-3sigma-specific functions is unknown. We
      demonstrate that endogenous 14-3-3sigma preferentially forms homodimers in cells.
      We have solved the x-ray crystal structure of 14-3-3sigma bound to an optimal
      phosphopeptide ligand at 2.4 angstroms resolution. The structure reveals the
      presence of stabilizing ring-ring and salt bridge interactions unique to the 14-3
      3sigma homodimer structure and potentially destabilizing electrostatic
      interactions between subunits in 14-3-3sigma-containing heterodimers,
      rationalizing preferential homodimerization of 14-3-3sigma in vivo. The
      interaction of the phosphopeptide with 14-3-3 reveals a conserved mechanism for
      phospho-dependent ligand binding, implying that the phosphopeptide binding cleft
      is not the critical determinant of the unique biological properties of 14-3
      3sigma. Instead, the structure suggests a second ligand binding site involved in
      14-3-3sigma-specific ligand discrimination. We have confirmed this by site
      directed mutagenesis of three sigma-specific residues that uniquely define this
      site. Mutation of these residues to the alternative sequence that is absolutely
      conserved in all other 14-3-3 isotypes confers upon 14-3-3sigma the ability to
      bind to Cdc25C, a ligand that is known to bind to other 14-3-3 proteins but not
      to sigma.

PMID- 15731108
TI  - S3-12, Adipophilin, and TIP47 package lipid in adipocytes.
AB  - Animals have evolved mechanisms to maintain circulating nutrient levels when
      energy demands exceed feeding opportunities. Mammals store most of their energy
      as triacylglycerol in the perilipin-coated lipid droplets of adipocytes. How
      newly synthesized triacylglycerol is delivered to perilipin-coated lipid droplets
      is poorly understood. Perilipin is a member of the evolutionarily related family
      of PAT proteins (Perilipin, Adipophilin, TIP47), which is defined by sequence
      similarity and association with lipid droplets. We previously showed that S3-12,
      which is also a member of this family, associates with a separate pool of lipid
      droplets that emerge when triacylglycerol storage is driven by adding oleate to
      the culture medium of adipocytes. Our current data extend these findings to
      demonstrate that nascent lipid droplets emerge with a coat composed of S3-12,
      TIP47, and adipophilin. After 100 min of oleate treatment, the nascent lipid
      droplets are more heterogeneous: S3-12 and TIP47 coat smaller, peripheral
      droplets and adipophilin coats a more medial population of droplets.
      Fractionation of untreated and oleate-treated adipocytes shows oleate-dependent
      redistribution of TIP47 and adipophilin from cytosolic fractions to the lipid
      droplet fraction. Inhibition of protein synthesis with cycloheximide does not
      block the oleate-induced formation of the nascent lipid droplets, nor does it
      prevent TAG accumulation. We suggest that the non-lipid droplet pools of S3-12,
      adipophilin, and TIP47 constitute a ready reservoir of coat proteins to permit
      rapid packaging of newly synthesized triacylglycerol and to maximize energy
      storage during nutrient excess.

PMID- 15731109
TI  - Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator
      activated receptor/retinoid X receptor heterodimers in the absence and presence
      of ligand.
AB  - In a global approach combining fluorescence recovery after photobleaching (FRAP),
      fluorescence correlation spectroscopy (FCS), and fluorescence resonance energy
      transfer (FRET), we address the behavior in living cells of the peroxisome
      proliferator-activated receptors (PPARs), a family of nuclear receptors involved
      in lipid and glucose metabolism, inflammation control, and wound healing. We
      first demonstrate that unlike several other nuclear receptors, PPARs do not form
      speckles upon ligand activation. The subnuclear structures that may be observed
      under some experimental conditions result from overexpression of the protein and
      our immunolabeling experiments suggest that these structures are subjected to
      degradation by the proteasome. Interestingly and in contrast to a general
      assumption, PPARs readily heterodimerize with retinoid X receptor (RXR) in the
      absence of ligand in living cells. PPAR diffusion coefficients indicate that all
      the receptors are engaged in complexes of very high molecular masses and/or
      interact with relatively immobile nuclear components. PPARs are not immobilized
      by ligand binding. However, they exhibit a ligand-induced reduction of mobility,
      probably due to enhanced interactions with cofactors and/or chromatin. Our study
      draws attention to the limitations and pitfalls of fluorescent chimera imaging
      and demonstrates the usefulness of the combination of FCS, FRAP, and FRET to
      assess the behavior of nuclear receptors and their mode of action in living
      cells.

PMID- 15731111
TI  - Paradoxical inhibition of protein aggregation and precipitation by
      transglutaminase-catalyzed intermolecular cross-linking.
AB  - Cross-linking of proteins catalyzed by tissue transglutaminase has been suggested
      to play key roles in a variety of cellular events, including cell apoptosis and
      human pathogenesis (e.g. polyglutamine and Alzheimer diseases). It has often been
      suggested that tissue transglutaminase enhances aggregation and precipitation of
      damaged or pathogenic proteins. To ascertain whether this is accurate, we
      investigated the effects of tissue transglutaminase-catalyzed modulation on the
      aggregation of structurally damaged and unfolded proteins. Our results indicated
      that the aggregation and precipitation of some unfolded proteins were inhibited
      by transglutaminasecatalyzed reaction, although the effect was strongly dependent
      upon the target protein species. To elucidate the molecular events underlying the
      inhibitory effect, extensive analysis was performed with regard to reduced beta
      lactoglobulin using a number of techniques, including chromatography and
      spectroscopy. The results indicated that cross-linking yields high molecular
      weight soluble polymers but inhibits the growth of insoluble aggregates. The
      cross-linked beta-lactoglobulin retained stable secondary structures with a
      hydrophobic core. We concluded that the transglutaminase-catalyzed intermolecular
      cross-linking did not necessarily enhance protein aggregation but could sometimes
      have a suppressive effect. The results of the present study suggested that tissue
      transglutaminase modifies aggregation and deposition of damaged or pathogenic
      proteins in vivo in a wide variety of manners depending on the target protein
      species and solution conditions.

PMID- 15731110
TI  - Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated
      cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular
      domains.
AB  - TRPM5, a member of the superfamily of transient receptor potential ion channels,
      is essential for the detection of bitter, sweet, and amino acid tastes. In
      heterologous cell types it forms a nonselective cation channel that is activated
      by intracellular Ca(2+). TRPM5 is likely to be part of the taste transduction
      cascade, and regulators of TRPM5 are likely to affect taste sensation. In this
      report we show that TRPM5, but not the related channel TRPM4b, is potently
      blocked by extracellular acidification. External acidification has two effects, a
      fast reversible block of the current (IC(50) pH = 6.2) and a slower irreversible
      enhancement of current inactivation. Mutation of a single Glu residue in the S3
      S4 linker and a His residue in the pore region each reduced sensitivity of TRPM5
      currents to fast acid block (IC(50) pH = 5.8 for both), and the double mutant was
      nearly insensitive to acidic pH (IC(50) pH = 5.0). Prolonged exposure to acidic
      pH enhanced inactivation of TRPM5 currents, and mutant channels that were less
      sensitive to acid block were also less sensitive to acid-enhanced inactivation,
      suggesting an intimate association between the two processes. These processes
      are, however, distinct because the pore mutant H896N, which has normal
      sensitivity to acid block, shows significant recovery from acid-enhanced
      inactivation. These data show that extracellular acidification acts through
      specific residues on TRPM5 to block conduction through two distinct but related
      mechanisms and suggest a possible interaction between extracellular pH and
      activation and adaptation of bitter, sweet, and amino acid taste transduction.

PMID- 15731112
TI  - Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor
      independent nucleomitochondrial translocation of RXRalpha/Nur77.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) induces apoptosis by its
      ability to bind insulin-like growth factors (IGFs) as well as its IGF-independent
      effects involving binding to other molecules including the retinoid X receptor
      alpha (RXRalpha). Here we describe that in response to IGFBP-3, the RXRalpha
      binding partner nuclear receptor Nur77 rapidly undergoes translocation from the
      nucleus to the mitochondria, initiating an apoptotic cascade resulting in caspase
      activation within 6 h. This translocation is a type 1 IGF receptor-signaling
      independent event as IGFBP-3 induces Nur77 translocation in R-cells. IGFBP-3 and
      Nur77 are additive in inducing apoptosis. GFP-Nur77 transfection into RXRalpha
      wild-type and knock-out mouse embryonic fibroblasts and subsequent treatment with
      IGFBP-3 show that RXRalpha is required for IGFBP-3-induced Nur77 translocation
      and apoptosis. Addition of IGFBP-3 to 22RV1 cell lysates enhanced the ability of
      GST-RXRalpha to "pull down" Nur77, and overexpression of IGFBP-3 enhanced the
      accumulation of mitochondrial RXRalpha. This unique nongenotropic nuclear pathway
      supports an emerging role for IGFBP-3 as a novel, multicompartmental signaling
      molecule involved in induction of apoptosis in malignant cells.

PMID- 15731114
TI  - Identification of four adenosine kinase isoforms in tobacco By-2 cells and their
      putative role in the cell cycle-regulated cytokinin metabolism.
AB  - Adenosine kinase (ADK), a key enzyme in the regulation of the intracellular level
      of adenosine is also speculated to be responsible for the conversion of cytokinin
      ribosides to their respective nucleotides. To elucidate the role of ADK in the
      cytokinin metabolism of tobacco BY-2 cells (Nicotiana tabacum cv. "Bright Yellow
      2"; TBY-2), we have identified and characterized the full-length cDNAs encoding
      four ADK isoforms of N. tabacum and determined their catalytic properties. The
      four TBY-2 ADK isoforms (designated 1S, 2S, 1T, and 2T) display a high affinity
      for both adenosine (Km 1.88-7.30 microm) and three distinct types of cytokinin
      ribosides: isopentenyladenosine; zeatin riboside; and dihydrozeatin riboside (Km
      0.30-8.71 microm). The Vmax/Km values suggest that ADK2S exhibits in vitro an
      overall higher efficiency in the metabolism of cytokinin ribosides than the other
      three isoforms. The expression pattern of NtADK genes is modulated significantly
      during the cell cycle. We suggest that the increased transcript accumulation of
      NtADK coupled to an increased ADK activity just prior to mitosis is associated
      with a very active cytokinin metabolism at that phase of the cell cycle of
      synchronized TBY-2 cells.

PMID- 15731113
TI  - Regulation of vascular smooth muscle proliferation by heparin: inhibition of
      cyclin-dependent kinase 2 activity by p27(kip1).
AB  - Uncontrolled proliferation of vascular smooth muscle cells (VSMCs) contribute to
      intimal hyperplasia during atherosclerosis and restenosis. Heparin is an
      antiproliferative agent for VSMCs and has been shown to block VSMC proliferation
      both in tissue culture systems and in animals. Despite the well documented
      antiproliferative actions of heparin, its cellular targets largely remain
      unknown. In an effort to characterize the mechanism of the antiproliferative
      property of heparin, we have analyzed the effect of heparin on cell cycle in
      VSMC. Our results indicate that the heparin-induced block in G(1) to S phase
      transition is imposed by p27(kip1)-mediated inhibition of cyclin-dependent kinase
      2 activity. Further analysis of p27(kip1) mRNA levels showed that the increase in
      p27(kip1) protein levels in heparin-treated VSMC occurs at posttranscriptional
      levels. We present evidence that heparin causes stabilization of p27(kip1)
      protein during G(1) phase and thereby prevents activation of cyclin-dependent
      kinase 2.

PMID- 15731115
TI  - Reactive oxygen species stimulates receptor activator of NF-kappaB ligand
      expression in osteoblast.
AB  - It has been established that reactive oxygen species (ROS) such as H2O2 or
      superoxide anion is involved in bone loss-related diseases by stimulating
      osteoclast differentiation and bone resorption and that receptor activator of NF
      kappaB ligand (RANKL) is a critical osteoclastogenic factor expressed on
      stromal/osteoblastic cells. However, the roles of ROS in RANKL expression and
      signaling mechanisms through which ROS regulates RANKL genes are not known. Here
      we report that increased intracellular ROS levels by H2O2 or xanthine/xanthine
      oxidase-generated superoxide anion stimulated RANKL mRNA and protein expression
      in human osteoblast-like MG63 cell line and primary mouse bone marrow stromal
      cells and calvarial osteoblasts. Further analysis revealed that ROS promoted
      phosphorylation of cAMP response element-binding protein (CREB)/ATF2 and its
      binding to CRE-domain in the murine RANKL promoter region. Moreover, the results
      of protein kinase A (PKA) inhibitor KT5720 and CREB1 RNA interference
      transfection clearly showed that PKA-CREB signaling pathway was necessary for ROS
      stimulation of RANKL in mouse osteoblasts. In human MG63 cells, however, we found
      that ROS promoted heat shock factor 2 (HSF2) binding to heat shock element in
      human RANKL promoter region and that HSF2, but not PKA, was required for ROS up
      regulation of RANKL as revealed by KT5720 and HSF2 RNA interference transfection.
      We also found that ROS stimulated phosphorylation of extracellular signal
      regulated kinases (ERKs) and that PD98059, the inhibitor for ERKs suppressed ROS
      induced RANKL expression either in mouse osteoblasts or in MG63 cells. These
      results demonstrate that ROS stimulates RANKL expression via ERKs and PKA-CREB
      pathway in mouse osteoblasts and via ERKs and HSF2 in human MG63 cells.

PMID- 15731116
TI  - Generation and characterization of SCARs by cloning and sequencing of RAPD
      products: a strategy for species-specific marker development in bamboo.
AB  - BACKGROUND AND AIMS: The aim of this study was to develop species-specific
      molecular markers for Bambusa balcooa and B. tulda to allow for their proper
      identification, in order to avoid unintentional adulteration that affects the
      quality and quantity of paper pulp production. METHODS: Two putative, species
      specific RAPD markers, Bb836 for B. balcooa and Bt609 for B. tulda were generated
      using a PCR-based RAPD technique. Species-specificity of these two markers was
      confirmed through Southern hybridization in which RAPD gels were blotted and
      hybridized with radiolabelled cloned RAPD markers. Southern hybridization
      analyses were also performed to validate homology of the co-migrating Bb836 and
      Bt609 marker bands amplified from 16 different populations of B. balcooa and B.
      tulda, respectively. Sequence-characterized amplified region (SCAR) markers were
      developed from Bb836 and Bt609 sequences, using 20-mer oligonucleotide primers
      designed from both the flanking ends of the respective RAPD primers. KEY RESULTS:
      As anticipated, Bb836 hybridized with an amplified band from B. balcooa and Bt609
      hybridized only with an amplified product from B. tulda; the two markers did not
      hybridize with the amplified products of any of the other 14 bamboo species
      studied. The two pairs of SCAR primers amplified the target sequences only in the
      respective species. The species-specific SCAR fragments were named as 'Balco836'
      for B. balcooa and 'Tuldo609' for B. tulda. The species-specific 'Balco836' was
      amplified from the genomic DNA of 80 individuals of 16 populations of B. balcooa
      studied. Similarly, the presence of 'Tuldo609' was noted in all the 80
      individuals representing 16 populations of B. tulda assessed. These SCAR
      fragments contained no obvious repetitive sequence beyond the primers.
      CONCLUSION: These two molecular markers are potentially useful for regulatory
      agencies to establish sovereign rights of the germplasms of B. balcooa and B.
      tulda. In addition, this is the first report of species-specific SCAR marker
      development in bamboo.

PMID- 15731118
TI  - Joint analysis of the NACP-REP1 marker within the alpha synuclein gene concludes
      association with alcohol dependence.
AB  - Various studies have linked alcohol dependence phenotypes to chromosome 4. One
      candidate gene is NACP (non-amyloid component of plaques), coding for alpha
      synuclein. Recently, it has been shown that alpha synuclein mRNA is increased in
      alcohol-dependent patients within withdrawal state. This increase is
      significantly associated with craving, especially obsessive craving. On the basis
      of these observations, the present study analysed two polymorphic repeats within
      the NACP gene. We found highly significant longer alleles of NACP-REP1 in alcohol
      dependent patients compared with healthy controls (Kruskal-Wallis test,
      chi(2)=99.5; df=3, P<0.001). In addition, these lengths significantly correlate
      with levels of expressed alpha synuclein mRNA (chi(2)=8.83; df=2, P=0.012). The
      present results point to a novel approach for a genetic determination of craving,
      a key factor in the genesis and maintenance not only of alcoholism but also of
      addiction in general.

PMID- 15731117
TI  - Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung
      cancer cells.
AB  - BRG1, also called SMARCA4, is the catalytic subunit of the SWI/SNF chromatin
      remodelling complex and influences transcriptional regulation by disrupting
      histone-DNA contacts in an ATP-dependent manner. BRG1 and other members of the
      SWI/SNF complex become inactivated in tumours, implying a role in cancer
      development. To understand the contribution of BRG1 to lung tumourigenesis, we
      restored BRG1 in H1299 lung cancer cells and used cDNA microarray analysis to
      identify changes in gene expression. Forty-three transcripts became activated,
      whereas two were repressed. Chromatin immunoprecipitation of resulting candidate
      genes revealed that the CYP3A4 and ZNF185 promoters recruited BRG1 and that
      recruitment to the CYP3A4 promoter was specific to this gene and did not involve
      the CYP3A5 or CYP3A7 family members. Moreover, specifically BRG1 but not its
      homologue BRM was recruited to the CYP3A4 and ZNF185 promoters. To explore their
      potential relevance in lung tumours, levels of CYP3A4 and ZNF185 transcripts were
      evaluated in seven additional lung cancer cell lines. CYP3A4 was undetectable in
      any of the lung cancer cells tested, and only the CYP3A5 family member was
      present in the A549 and Calu-3 cells. In contrast, the amount of ZNF185
      transcript clearly varied among lung cancer cell lines and severely reduced
      levels were observed in BRG1-deficient cells, except those of A427. We extended
      these observations to 27 lung primary tumours using real-time RT-PCR (TaqMan) and
      observed that four (15%) and 14 (52%) of them had BRG1 and ZNF185 downregulation,
      respectively, when compared with normal lung. No significant correlation between
      reduced levels of BRG1 and ZNF185 was observed, indicating that additional
      mechanisms to BRG1 inactivation may contribute to the loss of ZNF185 expression
      in lung tumours. In conclusion, our results provide evidence that transcriptional
      activation of ZNF185 and CYP3A4 is mediated by direct association of BRG1 with
      their promoters and also indicate that a decreased level of ZNF185 is a common
      feature of lung tumours and may be of biological relevance in lung
      carcinogenesis.

PMID- 15731119
TI  - Familial cases of point mutations in the XIST promoter reveal a correlation
      between CTCF binding and pre-emptive choices of X chromosome inactivation.
AB  - The choice mechanisms that determine the future inactive X chromosome in somatic
      cells of female mammals involve the regulated expression of the XIST gene. A
      familial C(-43)G mutation in the XIST promoter results in skewing of X chromosome
      inactivation (XCI) towards the inactive X chromosome of heterozygous females,
      whereas a C(-43)A mutation found primarily in the active X chromosome results in
      the opposite skewing pattern. Both mutations point to the existence of a factor
      that might be responsible for the skewed patterns. Here we identify this factor
      as CTCF, a conserved protein with a 11 Zn-finger (ZF) domain that can mediate
      multiple sequence-specificity and interactions between DNA-bound CTCF molecules.
      We show that mouse and human Xist/XIST promoters contain one homologous CTCF
      binding sequence with the matching dG-contacts, which in the human XIST include
      the -43 position within the DNase I footprint of CTCF. While the C(-43)A mutation
      abrogates CTCF binding, the C(-43)G mutation results in a dramatic increase in
      CTCF-binding efficiency by altering ZF-usage mode required for recognition of the
      altered dG-contacts of the mutant site. Thus, the skewing effect of the two -43C
      mutations correlates with their effects on CTCF binding. Finally, CTCF interacts
      with the XIST/Xist promoter only in female human and mouse cells. The
      interpretation that this reflected a preferential interaction with the promoter
      of the active Xist allele was confirmed in mouse fetal placenta. These
      observations are in keeping with the possibility that the choice of X chromosome
      inactivation reflects stabilization of a higher order chromatin conformation
      impinging on the CTCF-XIST promoter complex.

PMID- 15731120
TI  - Itching for a solution.

PMID- 15731121
TI  - Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment
      of atopic dermatitis: meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To determine the efficacy and tolerability of topical pimecrolimus and
      tacrolimus compared with other treatments for atopic dermatitis. DESIGN:
      Systematic review and meta-analysis. DATA SOURCES: Electronic searches of the
      Cochrane Library, Medline, and Embase. STUDY SELECTION: Randomised controlled
      trials of topical pimecrolimus or tacrolimus reporting efficacy outcomes or
      tolerability. DATA EXTRACTION:  EFFICACY: investigators' global assessment of
      response; patients' global assessment of response; proportions of patients with
      flares of atopic dermatitis; and improvements in quality of life. Tolerability:
      overall rates of withdrawal; withdrawal due to adverse events; and proportions of
      patients with burning of the skin and skin infections. DATA SYNTHESIS: 4186 of
      6897 participants in 25 randomised controlled trials received pimecrolimus or
      tacrolimus. Both drugs were significantly more effective than a vehicle control.
      Tacrolimus 0.1% was as effective as potent topical corticosteroids at three weeks
      and more effective than combined treatment with hydrocortisone butyrate 0.1%
      (potent used on trunk) plus hydrocortisone acetate 1% (weak used on face) at 12
      weeks (number needed to treat (NNT) = 6). Tacrolimus 0.1% was also more effective
      than hydrocortisone acetate 1% (NNT = 4). In comparison, tacrolimus 0.03% was
      more effective than hydrocortisone acetate 1% (NNT = 5) but less effective than
      hydrocortisone butyrate 0.1% (NNT = -8). Direct comparisons of tacrolimus 0.03%
      and tacrolimus 0.1% consistently favoured the higher strength formulation, but
      efficacy differed significantly between the two strengths only after 12 weeks'
      treatment (rate ratio 0.80, 95% confidence interval 0.65 to 0.99). Pimecrolimus
      was far less effective than betamethasone valerate 0.1% (NNT = -3 at three
      weeks). Pimecrolimus and tacrolimus caused significantly more skin burning than
      topical corticosteroids. Rates of skin infections in any of the comparisons did
      not differ. CONCLUSIONS: Both topical pimecrolimus and topical tacrolimus are
      more effective than placebo treatments for atopic dermatitis, but in the absence
      of studies that show long term safety gains, any advantage over topical
      corticosteroids is unclear. Topical tacrolimus is similar to potent topical
      corticosteroids and may have a place for long term use in patients with resistant
      atopic dermatitis on sites where side effects from topical corticosteroids might
      develop quickly. In the absence of key comparisons with mild corticosteroids, the
      clinical need for topical pimecrolimus is unclear. The usefulness of either
      treatment in patients who have failed to respond adequately to topical
      corticosteroids is also unclear.

PMID- 15731122
TI  - Treatment of irritable bowel syndrome.

PMID- 15731123
TI  - Primary care for children in the 21st century.

PMID- 15731125
TI  - Mortality from sickle cell disease in Africa.

PMID- 15731124
TI  - Ethics review of research and audit.

PMID- 15731126
TI  - Varicella vaccination for healthcare workers.

PMID- 15731127
TI  - Waiting times fall, but hospitals are still dirty, survey of patients shows.

PMID- 15731130
TI  - UK regulator to shame companies for misleading advertisements.

PMID- 15731128
TI  - FDA's safety reform is greeted with scepticism.

PMID- 15731132
TI  - Misdiagnosis raises questions about extent of avian flu epidemic.

PMID- 15731133
TI  - New suspension procedures aim to cut NHS disciplinary bill.

PMID- 15731134
TI  - Restraint should be last resort for violent behaviour.

PMID- 15731135
TI  - Sharp rise in deaths in South Africa is largely due to AIDS.

PMID- 15731136
TI  - US jury finds that antidepressant did not cause boy to kill his grandparents.

PMID- 15731138
TI  - NHS safety agency issues guidance on nasogastric tubes.

PMID- 15731140
TI  - Doctor who spoke out on public health issue is sued.

PMID- 15731139
TI  - NICE issues guidance for diagnosis and treatment of lung cancer.

PMID- 15731141
TI  - Conservatives promise to end waiting lists.

PMID- 15731142
TI  - FDA advisers warn: COX 2 inhibitors increase risk of heart attack and stroke.

PMID- 15731143
TI  - Nausea and vomiting due to insulin glargine in patient with type 1 diabetes
      mellitus.

PMID- 15731144
TI  - Recent developments in pain in dementia.

PMID- 15731145
TI  - Adolescents in primary care.

PMID- 15731147
TI  - Patients may be less risk averse than committees.

PMID- 15731146
TI  - Ethics, audit, and research: all shades of grey.

PMID- 15731148
TI  - Research ethics committees deserve support.

PMID- 15731149
TI  - Ethical review and ethical behaviour.

PMID- 15731150
TI  - My six day experience in the Middle East.

PMID- 15731151
TI  - Learning from low income countries: investing in traditional birth attendants may
      help reduce mortality in poor countries.

PMID- 15731152
TI  - Learning from low income countries: thalassaemia screening in Iran provides
      evidence for programme in Lancashire.

PMID- 15731153
TI  - Learning from low income countries: poor countries still provide reasons to train
      doctors in diseases of poverty.

PMID- 15731154
TI  - Learning from low income countries: experience in low income countries should
      count towards specialist registrar training.

PMID- 15731155
TI  - More on compulsory registration of clinical trials: GSK has created useful
      register.

PMID- 15731157
TI  - Learning from low income countries: poor patients deserve more science and less
      advocacy.

PMID- 15731158
TI  - Childhood deafness poses problems in developing countries.

PMID- 15731159
TI  - Pulmonary rehabilitation and readmissions in COPD: hospital readmissions did not
      fall.

PMID- 15731160
TI  - More on compulsory registration of clinical trials: complete clinical trial
      register is already reality for paediatrics.

PMID- 15731161
TI  - Branding treatment of children in rural India should be banned.

PMID- 15731163
TI  - Functional haplotypes in the promoter of matrix metalloproteinase-2 and lung
      cancer susceptibility.
AB  - Matrix metalloproteinase-2 (MMP-2) plays important roles in cancer initiation and
      progression. Our previous studies revealed that the -1306C-->T and -735C-->T
      polymorphisms in MMP2 promoter significantly influence transcriptional activity
      and their genotypes and haplotypes are associated with susceptibility to several
      cancers. This case-control study examined the contribution of these two
      polymorphisms to the risk of developing lung cancer. MMP2 genotypes and
      haplotypes were determined in 770 cases and 777 controls and the associations
      with risk of lung cancer were estimated by logistic regression. We observed a 2
      fold [odds ratio (OR), 2.12; 95% confidence interval (CI), 1.64-2.72] or 1.6-fold
      (OR, 1.57; 95% CI, 1.27-1.95) excess risk of developing lung cancer for the 
      1306CC or -735CC genotype carriers compared with non-carriers, respectively. A
      greater risk of lung cancer was associated with the C(-1306)-C(-735) haplotype
      (OR, 5.01; 95% CI, 2.57-9.78) compared with the T(-1306)-T(-735) haplotype,
      suggesting a synergic effect of these two polymorphisms. Furthermore, a greater
      than additive joint effect of the polymorphisms and smoking increased an even
      higher risk of lung cancer. The OR for smokers with the C(-1306)-C(-735)
      haplotype was 6.24 (95% CI, 4.51-8.64), which was significantly higher than that
      (OR, 4.10; 95% CI, 2.89-5.81) of smokers with the T(-1306) or T(-735)-containing
      haplotypes (P < 0.001). These results are consistent with our previous findings
      and further support the hypothesis that gain-of-function of MMP2 resulting from
      genetic polymorphisms plays an important role in human carcinogenesis.

PMID- 15731164
TI  - Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats
      by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a
      selective cyclooxygenase-2 inhibitor.
AB  - The chemopreventive efficacies of raloxifene and nimesulide, an anti-estrogen but
      with anti-androgen action and a cyclooxygenase-2 (COX-2) selective inhibitor,
      respectively, were evaluated in probasin/SV40 T antigen (Tag) transgenic (TG)
      rats. The treatment groups were placebo, nimesulide (400 p.p.m. in basal diet
      p.o.), raloxifene (slow-release pellets implanted s.c., 5 mg/kg/day), raloxifene
      (5 mg/kg/day) plus nimesulide (400 p.p.m.), and raloxifene (10 mg/kg/day) plus
      nimesulide (400 p.p.m.). Animals were killed at 17 weeks of age, and prostate
      tissues were harvested and weighed by lobes. Tissues were evaluated by histology,
      immunohistochemistry, and western blot analyses and blood was collected to
      measure the testosterone levels. All the animals in the placebo group had tumors
      in each lobe compared with only 43% each in the dorsolateral (DLP) and anterior
      prostate (AP) of the animals treated with raloxifene (10 mg/kg/day) plus
      nimesulide. The total prostate weights and adenocarcinoma portions were
      significantly reduced in the three raloxifene-treated groups, whereas atrophic
      glands were increased. There were no significant differences between the
      nimesulide alone and placebo groups or between the raloxifene (5 mg/kg/day) alone
      and raloxifene (5 mg/kg/day) plus nimesulide group, suggesting a lack of cancer
      preventive effects of the COX-2 inhibitor in this animal model. PCNA positive
      rates in ventral prostate (VP) and DLP, and androgen receptor (AR) levels in VP
      were significantly reduced in the three raloxifene-treated groups. Furthermore,
      circulating testosterone was decreased after raloxifene (10 mg/kg/day) plus
      nimesulide treatment. These results demonstrate that raloxifene, but not
      nimesulide, inhibits prostate carcinogenesis in SV40 Tag TG rats associated with
      a decline in circulating testosterone levels and a loss of AR expression, as well
      as an inhibition of cell proliferation.

PMID- 15731165
TI  - Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of
      cutaneous melanoma: a case-control study.
AB  - Individuals with the rare DNA repair deficiency syndrome xeroderma pigmentosum
      (XP) are sensitive to the sun and exhibit a 1000-fold increased risk for
      developing skin cancers, including cutaneous melanoma. Inherited polymorphisms of
      XP genes may contribute to subtle variations in DNA repair capacity and genetic
      susceptibility to melanoma. We investigated the role of three polymorphic alleles
      of the DNA repair gene XPC in a hospital-based case-control study of 294
      Caucasian patients from Germany who had cutaneous melanoma and 375 healthy cancer
      free sex-matched Caucasian control subjects from the same area. We confirmed that
      the XPC intron 9 PAT+, intron 11 -6A, and the exon 15 2920C polymorphisms are in
      a linkage disequilibrium. Only 1.6% of the 669 donors genotyped were discordant
      for these three polymorphisms. The allele frequencies (cases: controls) were for
      intron 9 PAT+ 41.7%:36.9%, for intron 11 -6A 41.8%:37.0% and for exon 15 2920C
      41.3%:37.3%. Using multivariate logistic regression analyses to control for age,
      skin type and number of nevi, the three polymorphisms were significantly
      associated with increased risks of melanoma: OR 1.87 (95% CI: 1.10-3.19; P =
      0.022), OR 1.83 (95% CI: 1.07-3.11; P = 0.026), and OR 1.82 (95% CI: 1.07-3.08; P
      = 0.026), respectively. Exploratory multivariate analyses of distinct subgroups
      revealed that these polymorphisms were associated with increased risks for the
      development of multiple primary melanomas (n = 28). The results of our case
      control study support the hypothesis that the intron 9 PAT+, intron 11 -6A and
      exon 15 2920C haplotype may contribute to the risk of developing cutaneous
      melanoma by increasing the rate of an alternatively spliced XPC mRNA isoform that
      skips exon 12 and leads to reduced DNA repair. Our results should be validated in
      independent samples in order to guard against false positive findings.

PMID- 15731166
TI  - CYP1A1 Val462 and NQO1 Ser187 polymorphisms, cigarette use, and risk for
      colorectal adenoma.
AB  - Cigarette use is a risk factor for colorectal adenoma, a known precursor of
      colorectal cancer. Polymorphic variants in NQO1 and CYP1A1 influence the
      activation of carcinogenic substances in tobacco smoke, possibly impacting on
      tobacco-associated risks for colorectal tumors. We investigated the association
      of cigarette smoking with risk for advanced colorectal adenoma in relation to the
      CYP1A1 Val(462) and NQO1 Ser(187) polymorphic variants. Subjects were 725 non
      Hispanic Caucasian cases with advanced colorectal adenoma of the distal colon
      (descending colon, sigmoid and rectum) and 729 gender- and ethnicity-matched
      controls, randomly selected from participants in the prostate, lung, colorectal
      and ovarian cancer screening trial. Subjects carrying either CYP1A1 Val(462) or
      NQO1 Ser(187) alleles were weakly associated with risk of colorectal adenoma;
      however, subjects carrying both CYP1A1 Val(462) and NQO1 Ser(187) alleles showed
      increased risks (OR = 2.2, 95% CI = 1.1-4.5), particularly among recent
      (including current) (OR = 17.4, 95% CI = 3.8-79.8, P for interaction = 0.02) and
      heavy cigarette smokers (>20 cigarettes/day) (OR = 21.1, 95% CI = 3.9-114.4, P
      for interaction = 0.03) compared with non-smokers who did not carry either of
      these variants. These genotypes were unassociated with risk in non-smokers. In
      analysis of adenoma subtypes, the combined gene variants were most strongly
      associated with the presence of multiple adenoma (P = 0.002). In summary, joint
      carriage of CYP1A1 Val(462) and NQO1 Ser(187) alleles, particularly in smokers,
      was related to colorectal adenoma risk, with a propensity for formation of
      multiple lesions.

PMID- 15731167
TI  - A comparison of somatic mutational spectra in healthy study populations from
      Russia, Sweden and USA.
AB  - A comparison of mutation spectra at the hypoxanthine-guanine phosphoribosyl
      transferase (HPRT) gene of peripheral blood T-lymphocytes may provide an insight
      into the aetiology of somatic mutation contributing to carcinogenesis and other
      diseases. To increase the knowledge of mutation spectra in healthy people, we
      have analysed HPRT mutant T-cells of 50 healthy Russians originally recruited as
      controls in a study involving Chernobyl clean-up workers [I.M. Jones, H.Galick,
      P.Kato et al. (2002) Radiat. Res., 158, 424-442]. Reverse transcriptase
      polymerase chain reactions and DNA sequencing identified 161 independent
      mutations among 176 thioguanine-resistant mutants. Forty mutations affected
      splicing mechanisms and 27 deletions or insertions of 1-60 nt were identified.
      Ninety-four single base substitutions were identified, including 62 different
      mutations at 55 different nucleotide positions, of which 19 had not been reported
      previously in human T-cells. Comparison of this base substitution spectrum with
      mutation spectra in a USA [K.J.Burkhart-Schultz, C.L. Thompson and I.M. Jones
      (1996) Carcinogenesis, 17, 1871-1883] and two Swedish populations [A.Podlutsky,
      A.-M.Osterholm, S.-M.Hou, A. Hofmaier and B. Lambert (1998) Carcinogenesis, 19,
      557-566; A.Podlutsky, S.M.Hou, F.Nyberg, G. Pershagen and B. Lambert (1999)
      Mutat. Res., 431, 325-39] revealed similarity in the type, frequency and
      distribution of mutations in the four spectra, consistent with aetiologies
      inherent in human metabolism. There were 15-19 identical mutations in the three
      pairwise comparisons of Russian with USA and Swedish spectra. Intriguingly, there
      were 21 mutations unique to the Russian spectrum, and comparison by the Monte
      Carlo method of W.T. Adams and T.R. Skopek [(1987) J. Mol. Biol., 194, 391-396]
      indicated that the Russian spectrum was different from both Swedish spectra (P =
      0.007, 0.002), but not different from the USA spectrum (P = 0.07) when Bonferroni
      correction for multiple comparisons was made (P < 0.008 required for
      significance). Age and smoking did not account for these differences. Other
      factors causing mutational differences need to be explored.

PMID- 15731168
TI  - Evolution of intratumoral genetic heterogeneity during colorectal cancer
      progression.
AB  - Evolution of intratumoral genetic heterogeneity during colorectal tumor
      progression has not been investigated so far. Multiple sample areas in colorectal
      adenocarcinoma at early and advanced stages and in metastases were studied for
      the well-known genetic alterations: K-ras and p53 point mutations and loss of
      heterozygosity (LOH) on chromosomes 5q and 18q. In primary colorectal cancers
      (CRCs), intratumoral genetic heterogeneity was more often observed in early than
      in advanced stages, at 90 and 67%, respectively. All but one of the advanced CRCs
      were composed of one predominant clone and other minor clones, whereas no
      predominant clone has been identified in half of the early cancers. At the early
      stage, the last events that were produced, the p53 mutation and LOH of 18q, were
      also the most heterogeneous. At the advanced stage, the LOH of 5q and 18q were
      the most frequent heterogeneous events (67 and 58%, respectively). The
      intratumoral heterogeneity for mutations was significantly reduced, from the
      early to the advanced stages (from 60 to 20% for K-ras and from 70 to 20% for
      p53). On the other hand, a quasi absence of intratumoral genetic heterogeneity
      was observed for K-ras and p53 in distant metastasis. In conclusion, colorectal
      adenocarcinomas are characterized by marked intratumoral genetic heterogeneity. A
      reduction of the intratumoral genetic heterogeneity for point mutations and a
      relative stability of the heterogeneity for allelic losses indicate that, during
      the progression of CRC, clonal selection and chromosome instability continue,
      while an increase cannot be proven.

PMID- 15731169
TI  - Periostin induction in tumor cell line explants and inhibition of in vitro cell
      growth by anti-periostin antibodies.
AB  - Several factors have been shown to promote the growth of colorectal cancers.
      Here, we provide evidence that periostin, a protein with structural and sequence
      homology with a TGF-beta-inducible gene, beta ig-h3, is upregulated in colorectal
      cancers and their liver metastasis, and it may play a role in promoting growth in
      these tumors. In vitro studies reveal that periostin promotes growth and cell
      proliferation in colorectal cancers and that this effect can be abrogated with
      antibodies to periostin. Furthermore, exposure of colorectal cancer cells to anti
      periostin antibodies activates apoptosis and potentiates the effects of 5
      fluorouracil chemotherapy. The results demonstrate the growth-promoting
      properties of periostin, and a possible role of targeting this protein as a
      therapeutic option in colorectal cancers.

PMID- 15731170
TI  - Epigenetic mechanisms in the dopamine D2 receptor-dependent inhibition of the
      prolactin gene.
AB  - Transcription of the prolactin gene is dynamically controlled by positive and
      negative hormone signals that target the regulatory promoter region. Based on the
      inducibility of prolactin gene expression by inhibitors of histone deacetylases
      (HDACs), we examined the role of histone acetylation at the genomic prolactin
      promoter as a late step in transcriptional regulation. Chromatin
      immunoprecipitation analysis of GH4 cells revealed elevated levels of acetylated
      histones in the promoter and enhancer regions of the gene, compared with
      downstream intron sequences. 17beta-Estradiol stimulated histone H4 acetylation
      in the promoter region by 2- to 3-fold within 30 min. Dopamine inhibited histone
      H4 acetylation by 2-fold in 30 min, an effect mimicked by the MAPK kinase (MEK1)
      inhibitor U0126. In contrast, the synthetic glucocorticoid dexamethasone, which
      inhibits prolactin transcription, failed to alter histone acetylation over the
      same time frame. Association of transcription activator Pit-1 with the prolactin
      promoter was unchanged by hormone treatment. However, in response to dopamine,
      histone deacetylase HDAC2 and corepressor mSin3A were rapidly recruited to the
      prolactin promoter, and association was sustained above basal levels over a 1-h
      period. Consistent with this corepressor function, depletion of endogenous mSin3A
      by small interfering RNA was sufficient to enhance prolactin gene expression by
      70%, comparable to the induction by the HDAC inhibitor, trichostatin A. These
      studies demonstrate that dopamine D2 receptor activation and inhibition of MAPK
      (ERK1/2) signaling lead to rapid deacetylation of histones at the genomic
      prolactin promoter. Recruitment of specific HDAC/ corepressor complexes may be an
      important mechanism for repression of target gene transcription by Gi/o-coupled
      receptors.

PMID- 15731172
TI  - Insights into the structure and molecular basis of ligand docking to the G
      protein-coupled secretin receptor using charge-modified amino-terminal agonist
      probes.
AB  - The amino terminus and third loop regions of class B G protein-coupled receptors
      play critical roles in ligand docking and action. For the prototypic secretin
      receptor, the hormone amino terminus is spatially approximated with receptor
      region high in transmembrane segment 6 (TM6), whereas residues ranging from
      position 6 through 26 label the amino terminus. Here, we focus on the role of
      charge of the secretin amino terminus, using a series of full-agonist, acetylated
      probes. Sites of covalent labeling were examined using sequential purification,
      chemical and enzymatic cleavage, and Edman degradation. High-affinity amino
      terminally-blocked probes labeled the distal amino-terminal tail, rather than
      TM6, while adding a basic residue, again labeled TM6. These data suggest that the
      secretin amino terminus docks between the amino terminus and TM6 of the receptor,
      with this region of secretin likely interacting with an acidic residue within the
      receptor TM6 and the third extracellular loop. To explore this, candidate acidic
      residues were mutated to Ala (E341A, D342A, E345A, E351A). The E351A mutant
      markedly interfered with binding, biological activity, and internalization,
      whereas all others bound secretin and signaled and internalized normally. This
      supports the possibility that there is a charge-charge interaction between this
      residue and the amino terminus of secretin that is critical to its normal
      docking.

PMID- 15731171
TI  - The androgen receptor directly targets the cellular Fas/FasL-associated death
      domain protein-like inhibitory protein gene to promote the androgen-independent
      growth of prostate cancer cells.
AB  - Androgens provide survival signals to prostate epithelial cells, and androgen
      ablation induces apoptosis in the prostate gland. However, the molecular
      mechanisms of actions of the androgen-signaling pathway in these processes are
      not fully understood. Here, we report that androgens induced expression of the
      cellular Fas/FasL-associated death domain protein-like inhibitory protein (c
      FLIP) gene, which is a potent inhibitor of Fas/FasL-mediated apoptosis. The
      androgen receptor was recruited to the promoter of the c-FLIP gene in the
      presence of androgens. We found that c-FLIP promoter contained multiple
      functional androgen response elements. In addition, we show that c-FLIP
      overexpression accelerated progression to androgen independence by inhibiting
      apoptosis in LNCaP prostate tumors implanted in nude mice. Our results suggest
      that the androgen receptor affects survival and apoptosis of prostate cells
      through regulation of the c-FLIP gene in response to androgens.

PMID- 15731173
TI  - Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant
      indicator of poor outcome in multiple myeloma.
AB  - In this study, we show that the hyaluronan synthase 1 (HAS1) gene undergoes
      aberrant intronic splicing in multiple myeloma (MM). In addition to HAS1 full
      length (HAS1(FL)), we identify 3 novel splice variants of HAS1, HAS1Va, HAS1Vb,
      and HAS1Vc, detected in patients with MM or monoclonal gammopathy of undetermined
      significance (MGUS). HAS1Vb and HAS1Vc undergo intronic splicing with creation of
      a premature stop codon. MM cells expressing one or more HAS1 variants synthesize
      extracellular and/or intracellular hyaluronan (HA). Expression of the HAS1Vb
      splice variant was significantly correlated with reduced survival (P = .001).
      Together, alternative HAS1 gene splicing, the correlations between HAS1 splicing
      and HA synthesis, and the correlations between HAS1 splicing and reduced survival
      of MM patients support the hypothesis that the family of HAS1 protein plays a
      significant role in disease progression. Further, expression of HAS1Vb, in
      conjunction with HAS1(FL) and/or other HAS1 variants, may lead to accumulation of
      intracellular HA molecules and an impact on receptor for HA-mediated motility
      (RHAMM)-mediated mitotic abnormalities in MM. This study highlights the potential
      importance of HAS1 and its alternative splicing in pathophysiology of MGUS and
      MM.

PMID- 15731174
TI  - Omenn syndrome due to ARTEMIS mutations.
AB  - Omenn syndrome (OS) is characterized by severe combined immunodeficiency (SCID)
      associated with erythrodermia, hepatosplenomegaly, lymphadenopathy, and alopecia.
      In patients with OS, B cells are mostly absent, T-cell counts are normal to
      elevated, and T cells are frequently activated and express a restricted T-cell
      receptor (TCR) repertoire. Thus far, inherited hypomorphic mutations of the
      recombination activating genes 1 and 2 (RAG1/2) have been described in OS. We
      report on a first patient with clinical and immunologic features of OS caused by
      hypomorphic ARTEMIS mutations. The patient's T cells expressed alpha/beta
      receptors with an oligoclonal repertoire but normal V(D)J recombination coding
      joints. Sequencing of the ARTEMIS gene revealed a compound heterozygosity in this
      nonhomologous end-joining (NHEJ) factor, explaining the enhanced radiosensitivity
      of the patient's primary dermal fibroblasts. The maternal allele contained a null
      mutation within the active center, whereas the expression of the paternal allele
      with a start codon (AUG to ACG) mutation partially restored V(D)J recombination
      and ARTEMIS function in vivo and in vitro.

PMID- 15731176
TI  - Intracellular interaction of von Willebrand factor and factor VIII depends on
      cellular context: lessons from platelet-expressed factor VIII.
AB  - We have previously reported that ectopically expressed factor VIII (FVIII) is
      stored within platelets and is released upon platelet activation. Studies by
      others in various cell lines have suggested that having von Willebrand factor
      (VWF) coexpression is necessary for FVIII granular storage and for its secretion.
      We tested the importance of VWF coexpression for ectopic storage of FVIII in
      platelets and for its bioavailability. Transgenic mice expressing platelet
      specific FVIII were crossed onto a VWF-/- background. Antigenic levels of
      platelet FVIII in these mice were nearly unchanged whether VWF was present or
      not. Whole-blood clotting times and FeCl3 carotid artery injury correction
      demonstrated that platelet FVIII demonstrably improved the bleeding diathesis in
      FVIIInull mice independent of the platelets' VWF status. Immunogold electron
      microscopy demonstrated that platelet FVIII is stored in platelet alpha-granules
      independent of the presence of VWF. It appears that FVIII's interaction with VWF
      and its intracellular transportation, storage, and secretion differ greatly
      depending on the cell type. The molecular basis for these differences now needs
      to be elucidated.

PMID- 15731175
TI  - Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation
      for acute myelogenous leukemia predicted by KIR and HLA genotypes.
AB  - Inhibitory killer immunoglobulin (Ig)-like receptors (KIRs) recognize HLA-C and 
      B epitopes on target cells, thereby regulating natural killer (NK) cell activity.
      In 178 patients receiving T-cell-depleted HLA-identical sibling transplants for
      acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute
      lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS), analysis of
      donor KIR genotype with HLA genotype demonstrated that 62.9% of the patients
      lacked an HLA ligand for donor-inhibitory KIR. Lack of HLA ligand for donor
      inhibitory KIR (missing KIR ligand) had no effect on disease-free survival (DFS),
      overall survival (OS), or relapse in patients receiving transplants for CML and
      ALL. In patients with AML and MDS, however, there was a significant missing KIR
      ligand effect on DFS (P = .014; hazard ratio [HR], 0.53; 95% confidence interval
      [95% CI], 0.28-0.88) and OS (P = .03; HR, 0.53; 95% CI, 0.3-0.93). Incidence of
      relapse was also lower in patients with AML and MDS who lacked the HLA ligand for
      donor-inhibitory KIR (P = .04; HR, 0.41; 95% CI, 0.18-0.97). AML and MDS patients
      lacking 2 HLA ligands for donor-inhibitory KIR had the highest DFS (P = .002) and
      OS (P = .003). There was no significant contribution of donor-activating KIR to
      transplantation outcome in these patients. These data indicate that the absence
      of class I ligand in the recipient for donor-inhibitory KIR can be a prognostic
      factor for transplantation outcome in HLA-identical sibling transplantation and
      that the lack of HLA-C or -B ligands for donor-inhibitory KIR can contribute to
      improved outcomes for patients with AML and MDS.

PMID- 15731177
TI  - Assessment of treatment-related myelodysplastic syndromes and acute myeloid
      leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and
      iodine I131 tositumomab.
AB  - The incidence of treatment-related myelodysplastic syndromes and acute myeloid
      leukemia (tMDSs/tAML) after tositumomab and iodine I(131) tositumomab
      administration to previously treated and untreated patients with non-Hodgkin
      lymphoma (NHL) was evaluated. A total of 1071 patients were enrolled in 7
      studies: 995 with relapsed/refractory low-grade NHL, +/- transformation (median,
      3 prior regimens [range, 1-13 regimens]) and 76 patients with previously
      untreated low-grade follicular NHL. A single dose of iodine tositumomab and
      I(131) tositumomab was administered. For tMDS/tAML patients, baseline and
      posttherapy peripheral blood and marrow specimens were reviewed in a blinded
      fashion. Median follow-up was 6 years from diagnosis and 2 years from
      radioimmunotherapy (RIT) for previously treated patients, and 4.6 years from
      radioimmunotherapy for previously untreated patients. tMDS/tAML was reported in
      35 (3.5%) of 995 patients (annualized incidence, 1.6%/y [95% confidence interval,
      1.0%-2.0%/y]), and 52% of the tMDS/tAML diagnoses of tMDS/tAML were confirmed in
      a blinded review (annualized incidence of 1.1%/y [95% confidence interval, 0.7%
      1.6%/y]). Of the 25 cases, 10 patients (40%) were diagnosed with tMDS/tAML prior
      to receiving radioimmunotherapy; 2 (8%) had no pathologic or clinical evidence to
      support such a diagnosis; and 13 (52%) were confirmed to have developed tMDS/tAML
      following RIT. This incidence is consistent with that expected on the basis of
      patients' prior chemotherapy for NHL. With a median follow-up approaching 5
      years, no case of tMDS/tAML has been reported in any of the 76 patients receiving
      iodine I(131) tositumomab as their initial therapy (P = .011 compared with
      previously treated patients).

PMID- 15731179
TI  - CLL, but not normal, B cells are dependent on autocrine VEGF and alpha4beta1
      integrin for chemokine-induced motility on and through endothelium.
AB  - Vascular endothelial cell growth factor (VEGF) is a multifunctional cytokine
      involved in tumor formation. In chronic lymphocytic leukemia (CLL), it is known
      that the malignant cells secrete VEGF and possess VEGF receptors. This suggests
      that an autocrine loop might be important in the pathogenesis of CLL. Here we
      show that, in patients with lymphadenopathy, autocrine VEGF and alpha(4)beta(1)
      integrin are involved in the chemokine-dependent motility of CLL cells on and
      through endothelium-processes important for the invasion of lymphoreticular
      tissues, a major determinant of disease outcome. In contrast, normal lymphocytes
      were not dependent on autocrine VEGF or alpha(4)beta(1) for either type of cell
      movement. Moreover, in contrast to normal B lymphocytes, CLL cells failed to
      cluster and activate alpha(L)beta(2) in response to chemokines, unless VEGF
      receptor(s) and alpha(4)beta(1) were also engaged by their respective ligands.
      This is the first demonstration that autocrine VEGF is involved in CLL-cell
      motility, and that the alpha(L)beta(2) on the malignant cells is functionally
      altered compared with that of normal B cells in not undergoing activation in
      response to chemokine alone. Given the importance of cell motility for tissue
      invasion, the present results provide a rationale for a trial of VEGF and
      alpha(4) blockade in patients with CLL who have tissue disease.

PMID- 15731178
TI  - Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an
      independent predictor of poor outcome.
AB  - Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the
      pathogenesis of many solid tumors, but little is known about its presence and
      role in hematologic neoplasms. Multiple myeloma (MM) is known to involve a
      deregulated cytokine network with secretion of inflammatory mediators. We thus
      decided to investigate the involvement of COX-2 in this neoplasm. Western
      blotting (WB) was used to evaluate 142 bone marrow (BM) specimens, including MM
      and monoclonal gammopathy of undetermined significance (MGUS). Selected cases
      under-went further evaluation by WB on purified CD138(+) cells,
      immunohistochemistry (IC), and real-time polymerase chain reaction (PCR) for mRNA
      expression. COX-2 was expressed in 11% (2 of 18) of MGUS specimens, 31% (29 of
      94) of MM at diagnosis, and 47% (14 of 30) of MM with relapsed/refractory
      disease. COX-2 positivity was associated with a poor outcome in terms of
      progression-free (18 vs 36 months; P < .001) and overall survival (28 vs 52
      months; P < .05). Real-time PCR showed COX-2 mRNA overexpression. IC and cell
      separation studies demonstrated COX-2 expression to be restricted to malignant
      plasma cells. This is the first report of the presence and prognostic role of COX
      2 expression in MM. Future studies will assess COX-2 involvement in other
      hematologic tumors and its potential use as a therapeutic or chemo-preventive
      target in onco-hematology.

PMID- 15731180
TI  - Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses.
AB  - Little is known about the ontogeny of naturally occurring CD4(+)CD25(+)
      regulatory/suppressor T cells that play a major role in maintaining self
      tolerance in mice and humans. In rodents, thymectomy on day 3 of life leads to
      multiple organ-specific autoimmune diseases that can be prevented by adoptive
      transfer of regulatory T cells, suggesting their neonatal development. We
      investigated regulatory T-cell ontogeny in 11 human fetuses. Together with the
      first mature T cells, thymic CD4(+)CD25(+) cells were detected as early as 13
      weeks of gestation. Thymic CD25(+) cells appeared to be positively selected at
      the CD4(+)CD8(+)CD3(hi) differentiation stage, as assessed by CD1a and CD69
      expression. The proportion of thymic CD4(+)CD25(+) cells appeared quite stable
      with age, around 6% to 7%, similar to the proportion observed in infant thymi.
      Extrathymic CD4(+)CD25(+) T cells could hardly be detected at 13 weeks of
      gestation but were present from week 14 onwards. As adult regulatory T cells,
      purified CD4(+)CD25(+) fetal cells were anergic and suppressed T-cell
      proliferative responses; they expressed intracellular cytotoxic T-lymphocyte
      associated antigen 4 (CTLA-4) and Foxp3 mRNA. Altogether, our results indicate
      that the generation of regulatory/suppressor T cells is consubstantial to the
      generation of a functional and self-tolerant immune system.

PMID- 15731181
TI  - Cytotoxic minor histocompatibility antigen HA-1-specific CD8+ effector memory T
      cells: artificial APCs pave the way for clinical application by potent primary in
      vitro induction.
AB  - Induction of cytotoxic T lymphocytes (CTLs) for treatment of relapsed leukemia
      after allogeneic stem-cell transplantation is hindered by the laborious and time
      consuming procedure of generating dendritic cells for antigen presentation.
      Artificial antigen-presenting cells (aAPCs) offer the advantage of being readily
      available in sufficient numbers, thus allowing for a highly standardized in vitro
      induction of CTLs. We generated aAPCs coated with anti-CD28 antibody (Ab) and
      either high-density (HD) or low-density (LD) major histocompatibility complex
      (MHC) class I molecules loaded with HA-1(H), a nonapeptide derived from the
      hematopoiesis-restricted minor histocompatibility antigen HA-1. HD- and LD-aAPCs
      potently induced HA-1(H)-specific CD8+ CTLs from untouched CD8+ T cells of
      healthy donors. CTLs were subsequently purified by magnetic-activated cell
      sorting. HD- as well as LD-aAPC-induced CTLs exerted high HA-1H-specific
      cytotoxicity, resembled T(c)1 effector memory cells, survived a long time in
      vitro, and were expanded by a factor varying between 8.2 x 10(4) and 51 x 10(4).
      The T-cell receptor (TCR) repertoire of HA-1H tetramer-positive CTLs was
      oligoclonal with a prominent usage of Vbeta6. The TCR repertoire of tetramer
      positive CTLs was distinct from and more restricted than that of tetramer
      negative cells. These findings indicate that aAPCs are attractive tools for the
      ex vivo generation of HA-1H-specific CTLs suitable for immunotherapy of relapsed
      leukemia.

PMID- 15731182
TI  - Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma:
      an analysis of prognostic factors from the Chronic Leukaemia Working Party of the
      EBMT.
AB  - We report the outcome of 229 patients who received an allograft for myeloma with
      reduced-intensity conditioning (RIC) regimens from 33 centers within the European
      Group for Blood and Marrow Transplantation (EBMT). The median age was 52 years
      and 64% were male. Conditioning regimens were heterogeneous, but most were
      fludarabine based and T cell depleted with antithymocyte globulin or alemtuzumab.
      Transplantation-related mortality (TRM) at 1 year was 22%. The 3-year overall
      survival (OS) and progression-free survival (PFS) were 41% and 21%, respectively.
      Adverse OS was associated with chemoresistant disease (relative risk [RR], 2.9),
      more than 1 prior transplantation (RR, 2.0), and male patients with female donors
      (RR, 1.45). Adverse PFS was associated with chemoresistance (RR, 2.4) and
      alemtuzumab (RR, 1.8). TRM was increased with female-to-male donation (RR, 2.5)
      and transplantation more than 1 year from diagnosis (RR, 2.3). Grades II to IV
      acute graft-versus-host disease (aGvHD) occurred in 31%. Chronic GvHD was
      associated with better OS and PFS and were 84% and 46% for limited, 58% and 30%
      for extensive, and 29% and 12% in its absence suggesting that a graft-versus
      myeloma effect is important. While RIC is feasible, heavily pretreated patients
      and patients with progressive disease do not benefit.

PMID- 15731183
TI  - Muscle tenderness from exercise: mechanisms?

PMID- 15731184
TI  - Visualization of localized store-operated calcium entry in mouse astrocytes.
      Close proximity to the endoplasmic reticulum.
AB  - Unloading of endoplasmic reticulum (ER) Ca(2+) stores activates influx of
      extracellular Ca(2+) through 'store-operated' Ca(2+) channels (SOCs) in the
      plasma membrane (PM) of most cells, including astrocytes. A key unresolved issue
      concerning SOC function is their spatial relationship to ER Ca(2+) stores. Here,
      using high resolution imaging with the membrane-associated Ca(2+) indicator, FFP
      18, it is shown that store-operated Ca(2+) entry (SOCE) in primary cultured mouse
      cortical astrocytes occurs at plasma membrane-ER junctions. In the absence of
      extracellular Ca(2+), depletion of ER Ca(2+) stores using cyclopiazonic acid, an
      ER Ca(2+)-ATPase inhibitor, and caffeine transiently increases the sub-plasma
      membrane Ca(2+) concentration ([Ca(2+)](SPM)) within a restricted space between
      the plasma membrane and adjacent ER. Restoration of extracellular Ca(2+) causes
      localized Ca(2+) influx that first increases [Ca(2+)](SPM) in the same restricted
      regions and then, with a delay, in ER-free regions. Antisense knockdown of the
      TRPC1 gene, proposed to encode endogenous SOCs, markedly reduces SOCE measured
      with Fura-2. High resolution immunocytochemistry with anti-TRPC1 antibody reveals
      that these TRPC-encoded SOCs are confined to the PM microdomains adjacent to the
      underlying 'junctional' ER. Thus, Ca(2+) entry through TRPC-encoded SOCs is
      closely linked, not only functionally, but also structurally, to the ER Ca(2+)
      stores.

PMID- 15731185
TI  - Functional properties of dopaminergic neurones in the mouse olfactory bulb.
AB  - The olfactory bulb of mammals contains a large population of dopaminergic
      interneurones within the glomerular layer. Dopamine has been shown both in vivo
      and in vitro to modulate several aspects of olfactory information processing, but
      the functional properties of dopaminergic neurones have never been described due
      to the inability to recognize these cells in living preparations. To overcome
      this difficulty, we used a transgenic mouse strain harbouring an eGFP (enhanced
      green fluorescent protein) reporter construct under the promoter of tyrosine
      hydroxylase, the rate-limiting enzyme for cathecolamine synthesis. As a result,
      we were able to identify dopaminergic neurones (TH-GFP cells) in living
      preparations and, for the first time, we could study the functional properties of
      such neurones in the olfactory bulb, in both slices and dissociated cells. The
      most prominent feature of these cells was the autorhythmicity. In these cells we
      identified five main voltage-dependent conductances: the two having largest
      amplitude were a fast transient Na(+) current and a delayed rectifier K(+)
      current. In addition, we observed three smaller inward currents, sustained by
      Na(+) ions (persistent type) and by Ca(2)(+) ions (LVA and HVA). Using
      pharmacological tools and ion substitution methods we showed that the pacemaking
      process is supported by the interplay of the persistent Na(+) current and of a T
      type Ca(2)(+) current. We carried out a complete kinetical analysis of the five
      conductances present in these cells, and developed a Hodgkin-Huxley model of TH
      GFP cells, capable of reproducing accurately the properties of living cells,
      including autorhytmicity, and allowing a precise understanding of the process.

PMID- 15731186
TI  - Early expression of AMPA receptors and lack of NMDA receptors in developing rat
      climbing fibre synapses.
AB  - Whether nascent glutamatergic synapses acquire their AMPA receptors
      constitutively or via a regulated pathway triggered by pre-existing NMDA receptor
      activation is still an open issue. Here, we provide evidence that some
      glutamatergic synapses develop without expressing NMDA receptors. Using
      immunocytochemistry, we showed that synapses between developing rat climbing
      fibres and Purkinje cells expressed GluR2-containing AMPA receptors as soon as
      they were formed (i.e. on embryonic day 19) but never carried detectable NMDA
      receptors. This was confirmed by electrophysiological recordings. Excitatory
      synaptic currents were recorded in Purkinje cells as early as P0. However, no
      NMDA receptor-mediated component was found in either spontaneous or evoked
      synaptic responses. In addition, we ruled out a possible role of extrasynaptic
      NMDA receptors by showing that AMPA receptor clustering at nascent climbing fibre
      synapses was not modified by chronic in utero NMDA receptor blockade.

PMID- 15731187
TI  - Developmental changes in expression of GABAA receptor-channels in rat intrinsic
      cardiac ganglion neurones.
AB  - The effects of gamma-aminobutyric acid (GABA) on the electrophysiological
      properties of intracardiac neurones were investigated in the intracardiac
      ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and
      adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory
      response in both intact and dissociated intracardiac ganglion neurones. Under
      voltage clamp, both GABA and muscimol elicited inward currents at -60 mV in a
      concentration-dependent manner. The fast, desensitizing currents were mimicked by
      the GABA(A) receptor agonists muscimol and taurine, and inhibited by the GABA(A)
      receptor antagonists, bicuculline and picrotoxin. The GABA(A0) antagonist
      (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on
      GABA-induced currents, suggesting that GABA(A) receptor-channels mediate the
      response. The GABA-evoked current amplitude recorded from dissociated neurones
      was age dependent whereby the peak current density measured at -100 mV was
      approximately 20 times higher for intracardiac neurones obtained from neonatal
      rats (P2-5) compared with adult rats (P45-49). The decrease in GABA sensitivity
      occurred during the first two postnatal weeks and coincides with maturation of
      the sympathetic innervation of the rat heart. Immunohistochemical staining using
      antibodies against GABA demonstrate the presence of GABA in the intracardiac
      ganglion plexus of the neonatal rat heart. Taken together, these results suggest
      that GABA and taurine may act as modulators of neurotransmission and cardiac
      function in the developing mammalian intrinsic cardiac nervous system.

PMID- 15731188
TI  - Regulation of activity-dependent dendritic vasopressin release from rat
      supraoptic neurones.
AB  - Magnocellular neurones of the hypothalamus release vasopressin and oxytocin from
      their dendrites and soma. Using a combination of electrophysiology,
      microdialysis, in vitro explants, and radioimmunoassay we assessed the
      involvement of intracellular Ca(2+) stores in the regulation of dendritic
      vasopressin release. Thapsigargin and cyclopiazonic acid, which mobilize Ca(2+)
      from intracellular stores of the endoplasmic reticulum, evoked vasopressin
      release from dendrites and somata of magnocellular neurones in the supraoptic
      nucleus. Thapsigargin also produced a dramatic potentiation of dendritic
      vasopressin release evoked by osmotic or high potassium stimulation. This effect
      is long lasting, time dependent, and specific to thapsigargin as caffeine and
      ryanodine had no effect. Furthermore, antidromic activation of electrical
      activity in the cell bodies released vasopressin from dendrites only after
      thapsigargin pretreatment. Thus, exposure to Ca(2+) mobilizers such as
      thapsigargin or cyclopiazonic acid primes the releasable pool of vasopressin in
      the dendrites, so that release can subsequently be evoked by electrical and
      depolarization-dependent activation. Vasopressin itself is effective in inducing
      dendritic vasopressin release, but it is ineffective in producing priming.

PMID- 15731189
TI  - Synchronization of enteric neuronal firing during the murine colonic MMC.
AB  - DiI (1,1'didodecyl-3,3,3',3'-tetramethylindocarbecyanine perchlorate) retrograde
      labelling and intracellular electrophysiological techniques were used to
      investigate the mechanisms underlying the generation of spontaneously occurring
      colonic migrating myoelectric complexes (colonic MMCs) in mice. In isolated,
      intact, whole colonic preparations, simultaneous intracellular electrical
      recordings were made from pairs of circular muscle (CM) cells during colonic MMC
      activity in the presence of nifedipine (1-2 microm). During the intervals between
      colonic MMCs, spontaneous inhibitory junction potentials (IJPs) were always
      present. The amplitudes of spontaneous IJPs were highly variable (range 1-20 mV)
      and occurred asynchronously in the two CM cells, when separated by 1 mm in the
      longitudinal axis. Colonic MMCs occurred every 151 +/- 7 s in the CM and
      consisted of a repetitive discharge of cholinergic rapid oscillations in membrane
      potential (range: 1-20 mV) that were superimposed on a slow membrane
      depolarization (mean amplitude: 9.6 +/- 0.5 mV; half-duration: 25.9 +/- 0.7 s).
      During the rising (depolarizing) phase of each colonic MMC, cholinergic rapid
      oscillations occurred simultaneously in both CM cells, even when the two
      electrodes were separated by up to 15 mm along the longitudinal axis of the
      colon. Smaller amplitude oscillations (< 5 mV) showed poor temporal correlation
      between two CM cells, even at short electrode separation distances (i.e. < 1 mm
      in the longitudinal axis). When the two electrodes were separated by 20 mm, all
      cholinergic rapid oscillations and IJPs in the CM (regardless of amplitude) were
      rarely, if ever, coordinated in time during the colonic MMC. Cholinergic rapid
      oscillations were blocked by atropine (1 microm) or tetrodotoxin (1 microm). Slow
      waves were never recorded from any CM cells. DiI labelling showed that the
      maximum projection length of CM motor neurones and interneurones along the bowel
      was 2.8 mm and 13 mm, respectively. When recordings were made adjacent to either
      oral or anal cut ends of the colon, the inhibitory or excitatory phases of the
      colonic MMC were absent, respectively. In summary, during the colonic MMC,
      cholinergic rapid oscillations of similar amplitudes occur simultaneously in two
      CM cells separated by large distances (up to 15 mm). As this distance was found
      to be far greater than the projection length of any single CM motor neurone, we
      suggest that the generation of each discrete cholinergic rapid oscillation
      represents a discreet cholinergic excitatory junction potential (EJP) that
      involves the synaptic activation of many cholinergic motor neurones
      simultaneously, by synchronous firing in many myenteric interneurones. Our data
      also suggest that ascending excitatory and descending inhibitory nerve pathways
      interact and reinforce each other.

PMID- 15731190
TI  - Ca2+-activated myosin-ATPases, creatine and adenylate kinases regulate
      mitochondrial function according to myofibre type in rabbit.
AB  - Mitochondrial respiration rates and their regulation by ADP, AMP and creatine,
      were studied at different free Ca(2+) concentrations (0.1 versus 0.4 microm) on
      permeabilized fibre bundles of rabbit skeletal muscles differing in their myosin
      heavy chain profiles. Four fibre bundle types were obtained: pure types I and
      IIx, and mixed types IIax (approximately 50% IIa and 50% IIx fibres) and IIb+
      (60% IIb fibres, plus IIx and IIa). At rest, pure type I fibres displayed a much
      higher apparent K(m) for ADP (212 microm) than IIx fibres (8 microm). Within the
      IIax and IIb+ mixed fibre bundle types, two K(ADP)(m) values were observed (70
      microm and 5 microm). Comparison between pure IIx and mixed types indicates that
      the intermediate K(m) of 70 microm most probably corresponds to the mitochondrial
      affinity for ADP in IIa fibres, the lowest K(m) for ADP (5 microm) corresponding
      to IIx and IIb types. Activation of mitochondrial creatine and adenylate kinase
      reactions stimulated mitochondrial respiration only in type I and IIax fibre
      bundles, indicating an efficient coupling between both kinases and ADP
      rephosphorylation in type I and, likely, IIa fibres, since no effect was observed
      in pure IIx fibres. Following Ca(2+)-induced activation of myosin-ATPase, an
      increase in mitochondrial sensitivity to ADP of 45% and 250% was observed in type
      IIax and I bundles, respectively, an effect mostly prevented by addition of
      vanadate, an inhibitor of myosin-ATPase. Ca(2+)-induced activation of myosin
      ATPase also prevented the stimulation of respiration rates by creatine and AMP in
      I and IIax bundles. In addition to differential regulation of mitochondrial
      respiration and energy transfer systems at rest in I and IIa versus IIx and IIb
      muscle fibres, our results indicate a regulation of phosphotransfer systems by
      Ca(2+) via the stimulation of myosin-ATPases in type I and IIa fibres of rabbit
      muscles.

PMID- 15731191
TI  - Blood flow in guinea fowl Numida meleagris as an indicator of energy expenditure
      by individual muscles during walking and running.
AB  - Running and walking are mechanically complex activities. Leg muscles must exert
      forces to support weight and provide stability, do work to accelerate the limbs
      and body centre of mass, and absorb work to act as brakes. Current understanding
      of energy use during legged locomotion has been limited by the lack of
      measurements of energy use by individual muscles. Our study is based on the
      correlation between blood flow and aerobic energy expenditure in active skeletal
      muscle during locomotion. This correlation is strongly supported by the available
      evidence concerning control of blood flow to active muscle, and the relationship
      between blood flow and the rate of muscle oxygen consumption. We used injectable
      microspheres to measure the blood flow to the hind-limb muscles, and other body
      tissues, in guinea fowl (Numida meleagris) at rest, and across a range of walking
      and running speeds. Combined with data concerning the various mechanical
      functions of the leg muscles, this approach has enabled the first direct
      estimates of the energetic costs of some of these functions. Cardiac output
      increased from 350 ml min(-1) at rest, to 1700 ml min(-1) at a running speed (
      approximately 2.6 m s(-1)) eliciting a of 90% of . The increase in cardiac output
      was achieved via approximately equal factorial increases in heart rate and stroke
      volume. Approximately 90% of the increased cardiac output was directed to the
      active muscles of the hind limbs, without redistribution of blood flow from the
      viscera. Values of mass-specific blood flow to the ventricles, approximately 15
      ml min(-1) g(-1), and one of the hind-limb muscles, approximately 9 ml min(-1) g(
      1), were the highest yet recorded for blood flow to active muscle. The patterns
      of increasing blood flow with increasing speed varied greatly among different
      muscles. The increases in flow correlated with the likely fibre type distribution
      of the muscles. Muscles expected to have many high-oxidative fibres
      preferentially increased flow at low exercise intensities. We estimated
      substantial energetic costs associated with swinging the limbs, co-contraction to
      stabilize the knee and work production by the hind-limb muscles. Our data provide
      a basis for evaluating hypotheses relating the mechanics and energetics of legged
      locomotion.

PMID- 15731192
TI  - Calcium transients in developing mouse skeletal muscle fibres.
AB  - Ca(2)(+) transients elicited by action potentials were measured using MagFluo-4,
      at 20-22 degrees C, in intact muscle fibres enzymatically dissociated from mice
      of different ages (7, 10, 15 and 42 days). The rise time of the transient (time
      from 10 to 90% of the peak) was 2.4 and 1.1 ms in fibres of 7- and 42-day-old
      mice, respectively. The decay of the transient was described by a double
      exponential function, with time constants of 1.8 and 16.4 ms in adult, and of 4.6
      and 105 ms in 7-day-old animals. The fractional recovery of the transient peak
      amplitude after 10 ms, F(2(10))/F(1), determined using twin pulses, was 0.53 for
      adult fibres and ranged between 0.03 and 0.60 in fibres of 7-day-old animals This
      large variance may indicate differences in the extent of inactivation of Ca(2)(+)
      release, possibly related to the difference in ryanodine receptor composition
      between young and old fibres. At the 7 and 10 day stages, fibres responded to
      Ca(2)(+)-free solutions with a larger decrease in the transient peak amplitude
      (25% versus 11% in adult fibres), possibly indicating a contribution of Ca(2)(+)
      influx to the Ca(2)(+) transient in younger animals. Cyclopiazonic acid (1 mum),
      an inhibitor of the sarcoplasmic reticulum (SR) Ca(2)(+)-ATPase, abolished the
      Ca(2)(+) transient decay in fibres of 7- and 10-day-old animals and significantly
      reduced its rate in older animals. Analysis of the transients with a Ca(2)(+)
      removal model showed that the results are consistent with a larger relative
      contribution of the SR Ca(2)(+) pump and a lower expression of myoplasmic
      Ca(2)(+) buffers in fibres of young versus old animals.

PMID- 15731193
TI  - Developmental processes and the induction of cardiovascular function: conceptual
      aspects.
AB  - The epidemiological basis of the developmental origins of disease concept is now
      widely accepted. The current impetus in research concerns establishing the
      underlying mechanisms. We discuss the wider biological nature of the phenomenon,
      with particular reference to 'maternal effects', the processes observed in many
      species by which the mother can induce phenotypic effects in her offspring.
      Animal models permit investigation of the induction of cardiovascular phenotypic
      attributes which resemble pathological effects in humans. We discuss the
      importance of transitions in aspects of the pre- versus the postnatal
      environment, with emphasis on nutrition and energy expenditure, and the critical
      role which the timing of environmental cues plays in inducing effects on the
      offspring. Coupled with the effects of specific maternal dietary components, the
      effects on the offspring are argued to involve epigenetic mechanisms. In this
      review we provide a conceptual framework for synthesising experimental and
      clinical data, important for considering the impact of the developmental origins
      concept in a life-course approach to the prevention of cardiovascular disease.

PMID- 15731194
TI  - A human congenital myasthenia-causing mutation (epsilon L78P) of the muscle
      nicotinic acetylcholine receptor with unusual single channel properties.
AB  - A mutation in the epsilon subunit of the human nicotinic acetylcholine receptor
      (epsilonL78P) is known to cause a congenital slow channel myasthenic syndrome. We
      have investigated the changes in receptor function that result in the mutant
      receptor producing prolonged endplate currents, and consequent muscle damage. The
      rate constants for channel gating and for the binding and dissociation of
      acetylcholine were investigated by analysis of single ion channel recordings. A
      conventional mechanism with two non-equivalent binding sites, and variations upon
      this mechanism, were fitted to data using a maximum likelihood method that uses
      the Hawkes-Jalali-Colquhoun (HJC) treatment of missed brief events. The mutant
      receptor produced prolonged activations, bursts of openings that cause a slow
      decay of simulated synaptic currents. The main reason for the longer bursts of
      openings seen with mutant receptor was a decrease in the rate of ACh dissociation
      from diliganded receptors, though the lifetime of individual openings was
      somewhat increased too. As well as producing long bursts, the mutant receptor
      also produced many very short openings, though these carry little current. The
      burst structure for the mutant receptor at low ACh concentration is unusual in
      that most long bursts appear to start in a very brief monoliganded open state
      that then usually binds another ACh molecule to produce a long diliganded
      activation. The first opening is so short that it will usually be missed
      (together with the shut time that follows it), so the true burst length is likely
      to be underestimated.

PMID- 15731196
TI  - Signal transduction pathway for the substance P-induced inhibition of rat Kir3
      (GIRK) channel.
AB  - Certain transmitters inhibit Kir3 (GIRK) channels, resulting in neuronal
      excitation. We analysed signalling mechanisms for substance P (SP)-induced Kir3
      inhibition in relation to the role of phosphatidylinositol 4,5-bisphosphate
      (PIP(2)). SP rapidly - with a half-time of approximately 10 s with intracellular
      GTPgammaS and approximately 14 s with intracellular GTP - inhibits a robustly
      activated Kir3.1/Kir3.2 current. A mutant Kir3 channel,
      Kir3.1(M223L)/Kir3.2(I234L), which has a stronger binding to PIP(2) than does the
      wild type Kir3.1/Kir3.2, is inhibited by SP as rapidly as the wild type
      Kir3.1/Kir3.2. This result contradicts the idea that Kir3 inhibition originates
      from the depletion of PIP(2). A Kir2.1 (IRK1) mutant, Kir2.1(R218Q), despite
      having a weaker binding to PIP(2) than wild type Kir3.1/Kir3.2, shows a SP
      induced inhibition slower than the wild type Kir3.1/Kir3.2 channel, again
      conflicting with the PIP(2) theory of channel inhibition. Co-immunoprecipitation
      reveals that Galpha(q) binds with Kir3.2, but not with Kir2.2 or Kir2.1. These
      functional results and co-immunoprecipitation data suggest that G(q) activation
      rapidly inhibits Kir3 (but not Kir2), possibly by direct binding of Galpha(q) to
      the channel.

PMID- 15731195
TI  - Electrical coupling and release of K+ from endothelial cells co-mediate ACh
      induced smooth muscle hyperpolarization in guinea-pig inner ear artery.
AB  - The physiological basis of ACh-elicited hyperpolarization in guinea-pig in vitro
      cochlear spiral modiolar artery (SMA) was investigated by intracellular recording
      combined with dye labelling of recorded cells and immunocytochemistry. We found
      the following. (1) The ACh-hyperpolarization was prominent only in cells that had
      a low resting potential (less negative than -60 mV). ACh-hyperpolarization was
      reversibly blocked by 4-DAMP, charybdotoxin or BAPTA-AM, but not by N(omega)
      nitro-L-arginine methyl ester, glipizide, indomethacin or 17-octadecynoic acid.
      (2) Ba(2)(+) (100 microm) and ouabain (1 microm) each attenuated ACh
      hyperpolarization by approximately 30% in smooth muscle cells (SMCs) but had only
      slight or no inhibition in endothelial cells (ECs). A combination of Ba(2)(+) and
      18beta-glycyrrhetinic acid near completely blocked the ACh-hyperpolarization in
      SMCs. (3) High K(+) (10 mm) induced a smaller hyperpolarization in ECs than in
      SMCs, with an amplitude ratio of 0.49 : 1. Ba(2)(+) blocked the K(+)-induced
      hyperpolarization by approximately 85% in both cell types, whereas ouabain
      inhibited K(+)-hyperpolarization differently in SMCs (19%) and ECs (35%) and
      increased input resistance. 18beta-Glycyrrhetinic acid blocked the high K(+)
      hyperpolarization in ECs only. (4) Weak myoendothelial dye coupling was detected
      by confocal microscopy in cells recorded with a propidium iodide-containing
      electrode for longer than 30 min. A sparse plexus of choline acetyltransferase
      immunoreactive (ChAT) fibres was observed around the SMA and its up-stream
      arteries. (5) Evoked excitatory junction potentials (EJP) were partially blocked
      by 4-DAMP in half of the cells tested. We conclude that ACh-induced
      hyperpolarization originates from ECs via activation of Ca(2)(+)-activated
      potassium channels, and is independent of the release of NO, cyclo-oxygenase or
      cytochrome P450 products. ACh-induced hyperpolarization in smooth muscle cells
      involves two mechanisms: (a) electrical spread of the hyperpolarization from the
      endothelium, and (b) activation of inward rectifier K(+) channels (K(ir)) and
      Na(+)-K(+) pump current by elevated interstitial K(+) released from the
      endothelial cells, these being responsible for about 60% and 40% of the
      hyperpolarization, respectively. The role ratio of K(ir) and pump current
      activation is at 8 : 1 or less.

PMID- 15731197
TI  - Comparative activity of quinolones (ciprofloxacin, levofloxacin, moxifloxacin and
      garenoxacin) against extracellular and intracellular infection by Listeria
      monocytogenes and Staphylococcus aureus in J774 macrophages.
AB  - OBJECTIVES: Quinolones accumulate in eukaryotic cells and show activity against a
      large array of intracellular organisms, but systematic studies aimed at examining
      their pharmacodynamic profile against intracellular bacteria are scarce. The
      present work aims at comparing intracellular-to-extracellular activities in this
      context. METHODS: We assessed the activities of ciprofloxacin, levofloxacin,
      moxifloxacin and garenoxacin against the extracellular (broth) and intracellular
      (infected J774 macrophages) forms of Listeria monocytogenes (cytosolic infection)
      and Staphylococcus aureus (phagolysosomal infection) using a range of clinically
      meaningful extracellular concentrations (0.06-4 mg/L). RESULTS: All four
      quinolones displayed concentration-dependent bactericidal activity against
      extracellular and intracellular L. monocytogenes and S. aureus for extracellular
      concentrations in the range 1-4-fold their MIC. Compared at equipotent
      extracellular concentrations, intracellular activities against L. monocytogenes
      were roughly equal to those that were extracellular, but were 50-100 times lower
      against S. aureus. Because quinolones accumulate in cells (ciprofloxacin,
      approximately 3 times; levofloxacin, approximately 5 times; garenoxacin,
      approximately 10 times, moxifloxacin, approximately 13 times), these data show
      that, intracellularly, quinolones are 5-10 times less potent against L.
      monocytogenes (P=0.065 [ANCOVA]), and at least 100 times less potent (P < 0.0001)
      against S. aureus. Because of their lower MICs and higher accumulation levels,
      garenoxacin and moxifloxacin were, however, more active than ciprofloxacin and
      levofloxacin when compared at similar extracellular concentrations. CONCLUSIONS:
      Quinolone activity is reduced intracellulary. This suggests that either only a
      fraction of cell-associated quinolones exert an antibacterial effect, or that
      intracellular activity is defeated by the local environment, or that
      intracellular bacteria only poorly respond to the action of quinolones.

PMID- 15731198
TI  - Comparison of gatifloxacin, moxifloxacin and ciprofloxacin for treatment of
      experimental Burkholderia pseudomallei infection.
AB  - OBJECTIVES: To compare the efficacy of moxifloxacin, gatifloxacin and
      ciprofloxacin for the post-exposure prophylaxis and treatment of experimental
      Burkholderia pseudomallei infection. The presence of persistent infection in
      treated animals and the rate of relapse following dexamethasone treatment were
      also investigated. METHODS: BALB/c mice were inoculated subcutaneously with 1.75
      x 10(6) cfu of B. pseudomallei strain 576. Gatifloxacin, moxifloxacin and
      ciprofloxacin (100 mg/kg) were given orally at 12 hourly intervals for 14 days
      starting at 6 h, 7 days or 12 days post-challenge. Control mice did not receive
      antibiotic therapy. RESULTS: No regimen gave 100% protection. Prophylaxis was
      most effective when started 6 h post-challenge, with survival rates at 42 days
      for ciprofloxacin, gatifloxacin and moxifloxacin being 58%, 75% and 75%,
      respectively. For treatment started at day 7 post-challenge, survival rates were
      17%, 11% and 44%, respectively. When antibiotic treatment was delayed until day
      12 post-challenge, survival rates fell to 21%, 17% and 28%, respectively.
      Following dexamethasone treatment of survivors at 42 days post-challenge,
      relapses occurred in all treatment groups. CONCLUSIONS: Fluoroquinolones do not
      provide good post-exposure protection against infection with B. pseudomallei. The
      newer agents moxifloxacin and gatifloxacin are not significantly better than
      ciprofloxacin for this purpose.

PMID- 15731199
TI  - Characterization of a Tn5382-like transposon containing the vanB2 gene cluster in
      a Clostridium strain isolated from human faeces.
AB  - OBJECTIVES: During a hospital surveillance programme to detect VRE carriers, an
      anaerobic vancomycin-resistant bacterial strain CCRI-9842 containing a vanB gene
      was isolated from a human faecal specimen. In this study, we have characterized
      this strain and its vanB-containing element. METHODS: Strain CCRI-9842 was
      characterized by 16S rDNA sequencing and susceptibility testing. PCR mapping and
      sequencing of the vanB-containing element, as well as plasmid extraction and
      mating experiments, were carried out to investigate the genetic basis of
      vancomycin resistance in this strain. RESULTS: Strain CCRI-9842 was identified as
      a Clostridium species closely related to Clostridium bolteae (96.8% 16S rDNA
      identity). This strain was resistant to a high level of vancomycin (MIC of 256
      mg/L), but was susceptible to teicoplanin and ampicillin. The complete sequence
      of the CCRI-9842 vanB gene exhibited 99.1% identity with that of vanB2. PCR
      mapping and sequencing showed that the genetic element carrying vanB2 was similar
      to transposon Tn5382/Tn1549. This Tn5382-like transposon forms circular
      intermediates and is flanked on the left and right ends by repeat sequences of at
      least 700 bp in the opposite direction. No plasmid was detected in this strain,
      suggesting that the Tn5382-like transposon was integrated into the chromosome.
      The vancomycin resistance was not transferable to enterococci. CONCLUSIONS: Our
      report shows for the first time the presence of a Tn5382-like transposon carrying
      vanB2 in a Clostridium species of the human intestinal flora. This suggests that
      the vanB2 Tn5382-like transposon is an important vector for the spread of
      vancomycin resistance in several bacterial species.

PMID- 15731200
TI  - Comparative evaluation of the nitrate reduction assay, the MTT test, and the
      resazurin microtitre assay for drug susceptibility testing of clinical isolates
      of Mycobacterium tuberculosis.
AB  - OBJECTIVES: To evaluate the performance of three rapid low-cost methods for the
      detection of resistance to first-line drugs in Mycobacterium tuberculosis.
      METHODS: One hundred M. tuberculosis clinical isolates were tested by the nitrate
      reductase assay (NRA), the MTT test and the resazurin microtitre assay (REMA),
      and the results compared with those obtained with the gold standard proportion
      method (PM) on Lowenstein Jensen medium. RESULTS: The results using the three
      methods showed a good sensitivity and specificity between 94% and 100% for the
      detection of rifampicin and isoniazid resistance. Specificity for ethambutol and
      streptomycin using MTT and resazurin was low (58-89%). In contrast, NRA showed a
      good agreement for all first-line drugs tested. CONCLUSIONS: This study shows a
      high level of agreement of these three low-cost methods compared with the PM for
      rapid detection of rifampicin and isoniazid resistance. However, more
      standardization is needed for ethambutol and streptomycin using the MTT test and
      resazurin microtitre assay. The nitrate reductase assay might represent an
      inexpensive procedure for rapid detection of resistance to first-line drugs in
      low-resource countries.

PMID- 15731201
TI  - Partial immune reconstitution following highly active antiretroviral therapy: can
      adjuvant interleukin-2 fill the gap?
AB  - Highly active antiretroviral therapy (HAART) induces a substantial control of HIV
      viral replication, but it allows for only a partial immune reconstitution, thus
      prompting the rationale for the adjuvant use of immunomodulants. Based on its in
      vitro action as a major T cell growth factor, interleukin (IL)-2 has now been
      extensively investigated for its potential to correct the HIV-driven immune
      deficiencies, possibly translating into immunological control over HIV infection.
      Specific immunological end points have thus far been addressed within extensive
      Phase I/II trials, disclosing a broad insight into several aspects of the IL-2
      mediated immune reconstitution allowing for interesting clinical speculation.
      Indeed, preliminary results indicate that adjuvant IL-2 induces a significant CD4
      cell rescue in patients with no immune recovery following long-term HAART, thus
      standing as a valid and safe therapeutic option for these patients. Furthermore,
      in these patients, the IL-2-mediated immune reconstitution is characterized by a
      rise in both peripheral turnover and de novo T cell synthesis, with reversion of
      the skewed HIV-driven immunophenotypic pattern, a substantial increase in IL-7
      production and in several markers of immune function. Combined, these findings
      indicate IL-2 has a beneficial effect in correcting the severe disruption in T
      cell homeostasis induced by HIV, through the interaction with T cells and
      cytokine microenvironment. However, whether or not these immunological effects
      translate into an actual immunological competency and therefore clinical benefit,
      still awaits demonstration from ongoing large, controlled clinical studies.

PMID- 15731202
TI  - Progression of liver fibrosis in patients coinfected with hepatitis C virus and
      human immunodeficiency virus undergoing antiretroviral therapy.
AB  - As the immunosuppression caused by human immunodeficiency virus (HIV) accelerates
      the progression of hepatitis C virus (HCV)-related liver fibrosis, the immune
      reconstitution associated with highly active antiretroviral therapy (HAART) may
      have the opposite effect. However, hepatotoxicity related to HAART could enhance
      the progression of liver fibrosis. Some retrospective studies have shown that
      therapy with the protease inhibitors may be associated with less severe liver
      fibrosis, whereas nevirapine use seems to correlate with faster progression. Low
      grade liver toxicity associated with nevirapine could account for this effect.
      However, other studies have not confirmed these findings. Long-term prospective
      studies are needed to analyse the impact of antiretroviral drugs on the
      progression of HCV-related liver disease. Meanwhile, no specific recommendations
      can be made on the use of individual drugs or drug classes in HIV/HCV-coinfected
      patients. Most importantly however, the inherent benefits of HAART largely
      outweigh the risk of enhancing fibrosis progression. Additionally, in coinfected
      patients, other factors that promote fibrogenesis, such as alcohol consumption,
      should be avoided. Antiviral treatment of chronic hepatitis C could also reduce
      the risk of liver damage associated with HAART.

PMID- 15731203
TI  - Physical linkage of Tn3 and part of Tn1721 in a tetracycline and ampicillin
      resistance plasmid from Salmonella Typhimurium.
AB  - OBJECTIVES: The complete nucleotide sequence of the 12 656 bp plasmid pFPTB1 from
      Salmonella enterica subsp. enterica serovar Typhimurium, which mediates
      resistance to tetracyclines and ampicillin, was determined. The plasmid was
      analysed for potential reading frames and structural features indicative of
      transposons and transposon relics. METHODS: Plasmid pFPTB1 was transformed into
      Escherichia coli JM109, overlapping restriction fragments were cloned into E.
      coli plasmid vectors and sequenced. In vitro susceptibility testing was carried
      out to confirm the resistance phenotype mediated by this plasmid. RESULTS:
      Plasmid pFPTB1 contains a complete Tn3-like transposon of 4950 bp consisting of
      the left terminal repeat, Tn3-related tnpR and tnpA genes for transposition
      functions, a novel gene for ampicillin resistance bla(TEM-135), and the right
      terminal repeat. Immediately downstream, the terminal 5215 bp at the right end of
      a Tn1721-like transposon, including the right terminal repeat, a truncated
      transposase gene, as well as the genes tet(A) and tetR for tetracycline
      resistance, were detected. A 5 bp direct repeat, TAAAA, was seen immediately
      upstream of the Tn3 part and immediately downstream of the Tn1721 part. Plasmid
      pFPTB1 also carries a replication region similar to that of the Klebsiella
      pneumoniae plasmid pJHCMW1. CONCLUSION: Plasmid pFPTB1 is one of the few
      completely sequenced plasmids from S. Typhimurium and harbours a novel transposon
      like structure consisting of a Tn3-related part containing the bla(TEM-135) gene
      for ampicillin resistance and a Tn1721-related part containing the tetR-tet(A)
      genes for tetracycline resistance.

PMID- 15731204
TI  - Haplotype reconstruction from SNP fragments by minimum error correction.
AB  - MOTIVATION: Haplotype reconstruction based on aligned single nucleotide
      polymorphism (SNP) fragments is to infer a pair of haplotypes from localized
      polymorphism data gathered through short genome fragment assembly. An important
      computational model of this problem is the minimum error correction (MEC) model,
      which has been mentioned in several literatures. The model retrieves a pair of
      haplotypes by correcting minimum number of SNPs in given genome fragments coming
      from an individual's DNA. RESULTS: In the first part of this paper, an exact
      algorithm for the MEC model is presented. Owing to the NP-hardness of the MEC
      model, we also design a genetic algorithm (GA). The designed GA is intended to
      solve large size problems and has very good performance. The strength and
      weakness of the MEC model are shown using experimental results on real data and
      simulation data. In the second part of this paper, to improve the MEC model for
      haplotype reconstruction, a new computational model is proposed, which
      simultaneously employs genotype information of an individual in the process of
      SNP correction, and is called MEC with genotype information (shortly, MEC/GI).
      Computational results on extensive datasets show that the new model has much
      higher accuracy in haplotype reconstruction than the pure MEC model.

PMID- 15731205
TI  - RNA tertiary structure determination: NOE pathways construction by tabu search.
AB  - MOTIVATION: Liquid state nuclear magnetic resonance (NMR) spectroscopy has now
      been well established as a method for RNA tertiary structure determination. Most
      of the steps involved in the determination of RNA molecules are performed using
      computer programs. They however, do not apply to resonance assignment being the
      starting point of the whole procedure. We propose a tabu search algorithm as a
      tool for automating this step. Nuclear overhause effect (NOE) pathway, which
      determines the assignment, is constructed during an analysis of possible
      connections between resonances within aromatic/anomeric region of two-dimensional
      NOESY spectrum resulting from appropriate NMR experiment. RESULTS: Computational
      tests demonstrate the superior performance of the tabu search algorithm as
      compared with the exact enumerative approach and genetic procedure applied to the
      experimental and simulated spectral data for RNA molecules. AVAILABILITY: The
      software package can be obtained upon request from Marta Szachniuk.

PMID- 15731206
TI  - PLATCOM: a Platform for Computational Comparative Genomics.
AB  - MOTIVATION: As more whole genome sequences become available, comparing multiple
      genomes at the sequence level can provide insight into new biological discovery.
      However, there are significant challenges for genome comparison. The challenge
      includes requirement for computational resources owing to the large volume of
      genome data. More importantly, since the choice of genomes to be compared is
      entirely subjective, there are too many choices for genome comparison. For these
      reasons, there is pressing need for bioinformatics systems for comparing multiple
      genomes where users can choose genomes to be compared freely. RESULTS: PLATCOM
      (Platform for Computational Comparative Genomics) is an integrated system for the
      comparative analysis of multiple genomes. The system is built on several public
      databases and a suite of genome analysis applications are provided as exemplary
      genome data mining tools over these internal databases. Researchers are able to
      visually investigate genomic sequence similarities, conserved gene neighborhoods,
      conserved metabolic pathways and putative gene fusion events among a set of
      selected multiple genomes. AVAILABILITY:
      http://platcom.informatics.indiana.edu/platcom

PMID- 15731207
TI  - Predicting a set of minimal free energy RNA secondary structures common to two
      sequences.
AB  - MOTIVATION: Function derives from structure, therefore, there is need for methods
      to predict functional RNA structures. RESULTS: The Dynalign algorithm, which
      predicts the lowest free energy secondary structure common to two unaligned RNA
      sequences, is extended to the prediction of a set of low-energy structures. Dot
      plots can be drawn to show all base pairs in structures within an energy
      increment. Dynalign predicts more well-defined structures than structure
      prediction using a single sequence; in 5S rRNA sequences, the average number of
      base pairs in structures with energy within 20% of the lowest energy structure is
      317 using Dynalign, but 569 using a single sequence. Structure prediction with
      Dynalign can also be constrained according to experiment or comparative analysis.
      The accuracy, measured as sensitivity and positive predictive value, of Dynalign
      is greater than predictions with a single sequence. AVAILABILITY: Dynalign can be
      downloaded at http://rna.urmc.rochester.edu

PMID- 15731208
TI  - A new measure of the robustness of biochemical networks.
AB  - MOTIVATION: The robustness of a biochemical network is defined as the tolerance
      of variations in kinetic parameters with respect to the maintenance of steady
      state. Robustness also plays an important role in the fail-safe mechanism in the
      evolutionary process of biochemical networks. The purposes of this paper are to
      use the synergism and saturation system (S-system) representation to describe a
      biochemical network and to develop a robustness measure of a biochemical network
      subject to variations in kinetic parameters. Since most biochemical networks in
      nature operate close to the steady state, we consider only the robustness
      measurement of a biochemical network at the steady state. RESULTS: We show that
      the upper bound of the tolerated parameter variations is related to the system
      matrix of a biochemical network at the steady state. Using this upper bound, we
      can calculate the tolerance (robustness) of a biochemical network without testing
      many parametric perturbations. We find that a biochemical network with a large
      tolerance can also better attenuate the effects of variations in rate parameters
      and environments. Compensatory parameter variations and network redundancy are
      found to be important mechanisms for the robustness of biochemical networks.
      Finally, four biochemical networks, such as a cascaded biochemical network, the
      glycolytic-glycogenolytic pathway in a perfused rat liver, the tricarboxylic acid
      cycle in Dictyostelium discoideum and the cAMP oscillation network in bacterial
      chemotaxis, are used to illustrate the usefulness of the proposed robustness
      measure.

PMID- 15731209
TI  - Self-organizing and self-correcting classifications of biological data.
AB  - MOTIVATION: Rapid, automated means of organizing biological data are required if
      we hope to keep abreast of the flood of data emanating from sequencing,
      microarray and similar high-throughput analyses. Faced with the need to validate
      the annotation of thousands of sequences and to generate biologically meaningful
      classifications based on the sequence data, we turned to statistical methods in
      order to automate these processes. RESULTS: An algorithm for automated
      classification based on evolutionary distance data was written in S. The
      algorithm was tested on a dataset of 1436 small subunit ribosomal RNA sequences
      and was able to classify the sequences according to an extant scheme, use
      statistical measurements of group membership to detect sequences that were
      misclassified within this scheme and produce a new classification. In this study,
      the use of the algorithm to address problems in prokaryotic taxonomy is
      discussed. AVAILABILITY: S-Plus is available from Insightful, Inc. An S-Plus
      implementation of the algorithm and the associated data are available at
      http://taxoweb.mmg.msu.edu/datasets

PMID- 15731210
TI  - Collateral missing value imputation: a new robust missing value estimation
      algorithm for microarray data.
AB  - MOTIVATION: Microarray data are used in a range of application areas in biology,
      although often it contains considerable numbers of missing values. These missing
      values can significantly affect subsequent statistical analysis and machine
      learning algorithms so there is a strong motivation to estimate these values as
      accurately as possible before using these algorithms. While many imputation
      algorithms have been proposed, more robust techniques need to be developed so
      that further analysis of biological data can be accurately undertaken. In this
      paper, an innovative missing value imputation algorithm called collateral missing
      value estimation (CMVE) is presented which uses multiple covariance-based
      imputation matrices for the final prediction of missing values. The matrices are
      computed and optimized using least square regression and linear programming
      methods. RESULTS: The new CMVE algorithm has been compared with existing
      estimation techniques including Bayesian principal component analysis imputation
      (BPCA), least square impute (LSImpute) and K-nearest neighbour (KNN). All these
      methods were rigorously tested to estimate missing values in three separate non
      time series (ovarian cancer based) and one time series (yeast sporulation)
      dataset. Each method was quantitatively analyzed using the normalized root mean
      square (NRMS) error measure, covering a wide range of randomly introduced missing
      value probabilities from 0.01 to 0.2. Experiments were also undertaken on the
      yeast dataset, which comprised 1.7% actual missing values, to test the hypothesis
      that CMVE performed better not only for randomly occurring but also for a real
      distribution of missing values. The results confirmed that CMVE consistently
      demonstrated superior and robust estimation capability of missing values compared
      with other methods for both series types of data, for the same order of
      computational complexity. A concise theoretical framework has also been
      formulated to validate the improved performance of the CMVE algorithm.
      AVAILABILITY: The CMVE software is available upon request from the authors.

PMID- 15731211
TI  - Object-oriented biological system integration: a SARS coronavirus example.
AB  - MOTIVATION: The importance of studying biology at the system level has been well
      recognized, yet there is no well-defined process or consistent methodology to
      integrate and represent biological information at this level. To overcome this
      hurdle, a blending of disciplines such as computer science and biology is
      necessary. RESULTS: By applying an adapted, sequential software engineering
      process, a complex biological system (severe acquired respiratory syndrome
      coronavirus viral infection) has been reverse-engineered and represented as an
      object-oriented software system. The scalability of this object-oriented software
      engineering approach indicates that we can apply this technology for the
      integration of large complex biological systems. AVAILABILITY: A navigable web
      based version of the system is freely available at
      http://people.musc.edu/~zhengw/SARS/Software-Process.htm

PMID- 15731212
TI  - DATF: a database of Arabidopsis transcription factors.
AB  - We have probably developed the most comprehensive database of Arabidopsis
      transcription factors (DATF). The DATF contains known and predicted Arabidopsis
      transcription factors (1827 genes in 56 families) with the unique information of
      1177 cloned sequences and many other features including 3D structure templates,
      EST expression information, transcription factor binding sites and nuclear
      location signals. AVAILABILITY: DATF is freely available at
      http://datf.cbi.pku.edu.cn

PMID- 15731213
TI  - Using evolutionary Expectation Maximization to estimate indel rates.
AB  - MOTIVATION: The Expectation Maximization (EM) algorithm, in the form of the Baum
      Welch algorithm (for hidden Markov models) or the Inside-Outside algorithm (for
      stochastic context-free grammars), is a powerful way to estimate the parameters
      of stochastic grammars for biological sequence analysis. To use this algorithm
      for multiple-sequence evolutionary modelling, it would be useful to apply the EM
      algorithm to estimate not only the probability parameters of the stochastic
      grammar, but also the instantaneous mutation rates of the underlying evolutionary
      model (to facilitate the development of stochastic grammars based on phylogenetic
      trees, also known as Statistical Alignment). Recently, we showed how to do this
      for the point substitution component of the evolutionary process; here, we extend
      these results to the indel process. RESULTS: We present an algorithm for maximum
      likelihood estimation of insertion and deletion rates from multiple sequence
      alignments, using EM, under the single-residue indel model owing to Thorne,
      Kishino and Felsenstein (the 'TKF91' model). The algorithm converges extremely
      rapidly, gives accurate results on simulated data that are an improvement over
      parsimonious estimates (which are shown to underestimate the true indel rate),
      and gives plausible results on experimental data (coronavirus envelope domains).
      Owing to the algorithm's close similarity to the Baum-Welch algorithm for
      training hidden Markov models, it can be used in an 'unsupervised' fashion to
      estimate rates for unaligned sequences, or estimate several sets of rates for
      sequences with heterogenous rates. AVAILABILITY: Software implementing the
      algorithm and the benchmark is available under GPL from http://www.biowiki.org/

PMID- 15731214
TI  - Novel repeated DNA sequences in safflower (Carthamus tinctorius L.) (Asteraceae):
      cloning, sequencing, and physical mapping by fluorescence in situ hybridization.
AB  - Two novel repetitive DNA sequences, pCtKpnI-1 and pCtKpnI-2, were isolated from
      Carthamus tinctorius (2n = 2x = 24) and cloned. Both represent tandemly repeated
      sequences. The pCtKpnI-1 and pCtKpnI-2 clones constitute repeat units of 343-345
      bp and 367 bp, respectively, with 63% sequence heterogeneity between the two.
      Fluorescence in situ hybridization (FISH) was employed on metaphase chromosomes
      of C. tinctorius using, simultaneously, pCtKpnI-1 and pCtKpnI-2 repeated
      sequences. The pCtKpnI-1 sequence was found to be exclusively localized at
      subtelomeric regions on most of the chromosomes. On the other hand, sequence of
      the pCtKpnI-2 clone was distributed on two nucleolar and one nonnucleolar
      chromosome pairs. The satellite, and the intervening chromosome segment between
      the primary and secondary constrictions, in the two nucleolar chromosome pairs
      were wholly constituted by pCtKpnI-2 repeated sequence. The pCtKpnI-2 repeated
      sequence, showing partial homology to intergenic spacer (IGS) of 18S-25S
      ribosomal RNA genes of an Asteraceae taxon (Centaurea stoebe), and the 18S-25S
      rRNA gene clusters were located at independent, but juxtaposed sites in the
      nucleolar chromosomes. Variability in the number, size, and location of the two
      repeated sequences provided identification of most of the chromosomes in the
      otherwise not too distinctive homologues within the complement. This article
      reports the start of a molecular cytogenetics program targeting the genome of
      safflower, a major world oil crop about whose genetics very little is known.

PMID- 15731215
TI  - Genetic differentiation among populations of the salt marsh beetle Pogonus
      littoralis (Coleoptera: Carabidae): a comparison between Atlantic and
      Mediterranean populations.
AB  - Genetic differentiation was studied among populations of the salt marsh beetle
      Pogonus littoralis (Coleoptera: Carabidae), comparing Atlantic and Mediterranean
      populations over a large part of its range. The genetic structure of this highly
      mobile beetle was investigated by studying allozyme polymorphism at nine enzyme
      loci in 13 populations. Mediterranean P. littoralis were highly significantly
      differentiated from Atlantic populations. Moreover, more isolated Atlantic
      populations showed increased differentiation and decreased genetic diversity
      compared to less fragmented Mediterranean populations.

PMID- 15731216
TI  - Structure of the mitochondrial control region of the Eurasian otter (Lutra lutra;
      Carnivora, Mustelidae): patterns of genetic heterogeneity and implications for
      conservation of the species in Italy.
AB  - In this study we determined the complete sequence of the mitochondrial DNA
      (mtDNA) control region of the Eurasian otter (Lutra lutra). We then compared
      these new sequences with orthologues of nine carnivores belonging to six families
      (Mustelidae, Mephitidae, Canidae, Hyaenidae, Ursidae, and Felidae). The
      comparative analyses identified all the conserved regions previously found in
      mammals. The Eurasian otter and seven other species have a single location with
      tandem repeats in the right domain, while the spotted hyena (Hyaenidae) and the
      tiger (Felidae) have repeated sequences in both the right and left domains. To
      assess the degree of genetic heterogeneity of the Eurasian otter in Italy we
      sequenced two fragments of the gene and analyzed length polymorphisms of repeated
      sequences and heteroplasmy in 32 specimens. The study includes 23 museum
      specimens collected in northern, central, and southern Italy; most of these
      specimens are from extinct populations, while the southern Italian samples belong
      to the sole extant Italian population of the Eurasian otter. The study also
      includes all the captive-reared animals living in the colony "Centro Lontra,
      Caramanico Terme" (Pescara, central Italy). The colony is maintained for
      reintroduction of the species. We found a low level of genetic polymorphism; a
      single haplotype is dominant, but our data indicate the presence in central and
      southern Italy of two slightly divergent haplotypes. One haplotype belongs to an
      extinct population, the other is present in the single extant Italian population.
      Analyses of length polymorphisms and heteroplasmy indicate that the autochthonous
      Italian samples are characterized by a distinct array of repeated sequences from
      captive-reared animals.

PMID- 15731217
TI  - Is a large-scale DNA-based inventory of ancient life possible?
AB  - A complete DNA-based inventory of the Earth's present biota using large-scale
      high-throughput DNA sequencing of signature region(s) (DNA barcoding) is an
      ambitious proposal rivaling the Human Genome Project. We examine whether this
      approach will also enable us to assess the past diversity of the earth's biota.
      To test this, we sequenced the 5' terminus of the mitochondrial cytochrome c
      oxidase I (COI) gene of individuals belonging to a group of extinct ratite birds,
      the moa of New Zealand. Moa comprised a large number of taxa that radiated in
      isolation on this oceanic landmass. Using a phylogenetic approach based on a
      large data set including protein coding and 12S DNA sequences as well as
      morphology, we now have precise information about the number of moa species that
      once existed. We show that each of the moa species detected using this extensive
      data set has a unique COI barcode(s) and that they all show low levels of within
      species COI variation. Consequently, we conclude that COI sequences accurately
      identify the species discovered using the larger data set. Hence, more generally,
      this study suggests that DNA barcoding might also help us detect other extinct
      animal species and that a large-scale inventory of ancient life is possible.

PMID- 15731218
TI  - Dual mechanisms of pestiviral superinfection exclusion at entry and RNA
      replication.
AB  - For many viruses, primary infection has been shown to prevent superinfection by a
      homologous second virus. In this study, we investigated superinfection exclusion
      of bovine viral diarrhea virus (BVDV), a positive-sense RNA pestivirus. Cells
      acutely infected with BVDV were protected from superinfection by homologous BVDV
      but not with heterologous vesicular stomatitis virus. Superinfection exclusion
      was established within 30 to 60 min but was lost upon passaging of persistently
      infected cells. Superinfecting BVDV failed to deliver a translatable genome into
      acutely infected cells, indicating a block in viral entry. Deletion of structural
      protein E2 from primary infecting BVDV abolished this exclusion. Bypassing the
      entry block by RNA transfection revealed a second block at the level of
      replication but not translation. This exclusion did not require structural
      protein expression and was inversely correlated with the level of primary BVDV
      RNA replication. These findings suggest dual mechanisms of pestivirus
      superinfection exclusion, one at the level of viral entry that requires viral
      glycoprotein E2 and a second at the level of viral RNA replication.

PMID- 15731219
TI  - Signature for long-term vaccine-mediated control of a Simian and human
      immunodeficiency virus 89.6P challenge: stable low-breadth and low-frequency T
      cell response capable of coproducing gamma interferon and interleukin-2.
AB  - In 2001, we reported 20 weeks of control of challenge with the virulent 89.6P
      chimera of simian and human immunodeficiency viruses (SHIV-89.6P) by a Gag-Pol
      Env vaccine consisting of DNA priming and modified vaccinia virus Ankara
      boosting. Here we report that 22 out of 23 of these animals successfully
      controlled their viremia until their time of euthanasia at 200 weeks
      postchallenge. At euthanasia, all animals had low to undetectable viral loads and
      normal CD4 counts. During the long period of viral control, gamma interferon (IFN
      gamma)-producing antiviral T cells were present at unexpectedly low breadths and
      frequencies. Most animals recognized two CD8 and one CD4 epitope and had
      frequencies of IFN-gamma-responding T cells from 0.01 to 0.3% of total CD8 or CD4
      T cells. T-cell responses were remarkably stable over time and, unlike responses
      in most immunodeficiency virus infections, maintained good functional
      characteristics, as evidenced by coproduction of IFN-gamma and interleukin-2.
      Overall, high titers of binding and neutralizing antibody persisted throughout
      the postchallenge period. Encouragingly, long-term control was effective in
      macaques of diverse histocompatibility types.

PMID- 15731220
TI  - Functional interaction of heterogeneous nuclear ribonucleoprotein C with
      poliovirus RNA synthesis initiation complexes.
AB  - We had previously demonstrated that a cellular protein specifically interacts
      with the 3' end of poliovirus negative-strand RNA. We now report the identity of
      this protein as heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. Formation
      of an RNP complex with poliovirus RNA was severely impaired by substitution of a
      lysine, highly conserved among vertebrates, with glutamine in the RNA recognition
      motif (RRM) of recombinant hnRNP C1, suggesting that the binding is mediated by
      the RRM in the protein. We have also shown that in a glutathione S-transferase
      (GST) pull-down assay, GST/hnRNP C1 binds to poliovirus polypeptide 3CD, a
      precursor to the viral RNA-dependent RNA polymerase, 3D(pol), as well as to P2
      and P3, precursors to the nonstructural proteins. Truncation of the auxiliary
      domain in hnRNP C1 (C1DeltaC) diminished these protein-protein interactions. When
      GST/hnRNP C1DeltaC was added to in vitro replication reactions, a significant
      reduction in RNA synthesis was observed in contrast to reactions supplemented
      with wild-type fusion protein. Indirect functional depletion of hnRNP C from in
      vitro replication reactions, using poliovirus negative-strand cloverleaf RNA, led
      to a decrease in RNA synthesis. The addition of GST/hnRNP C1 to the reactions
      rescued RNA synthesis to near mock-depleted levels. Furthermore, we demonstrated
      that poliovirus positive-strand and negative-strand RNA present in cytoplasmic
      extracts prepared from infected HeLa cells coimmunoprecipitated with hnRNP C1/C2.
      Our findings suggest that hnRNP C1 has a role in positive-strand RNA synthesis in
      poliovirus-infected cells, possibly at the level of initiation.

PMID- 15731221
TI  - E1A-CR3 interaction-dependent and -independent functions of mSur2 in viral
      replication of early region 1A mutants of mouse adenovirus type 1.
AB  - mSur2, a subunit of the Mediator complex, is required for efficient mouse
      adenovirus type 1 (MAV-1) replication (L. Fang, J. L. Stevens, A. J. Berk, and K.
      R. Spindler, J. Virol. 78:12888-12900, 2004). We examined the contributions of
      early-region 1A (E1A) to mSur2 function in MAV-1 replication with E1A mutant
      viruses. At a multiplicity of infection (MOI) of 1, viruses containing CR3
      replicated better in Sur2+/+ mouse embryonic fibroblasts (MEFs) than in Sur2-/-
      MEFs. In contrast, viruses lacking CR3 replicated no better in Sur2+/+ than in
      Sur2-/- MEFs. This result supports the hypothesis that the E1A CR3-mSur2
      interaction is important for MAV-1 replication. However, at an MOI of 0.05,
      viruses lacking CR3 showed replication defects in Sur2-/- MEFs compared to
      Sur2+/+ MEFs, suggesting an E1A CR3 interaction-independent function of mSur2 in
      MAV-1 replication in cell culture. Paradoxically, CR1Delta, CR2Delta, and
      CR3Delta mutant viruses replicated slightly more efficiently than wild-type (wt)
      MAV-1 and E1A null mutant viruses in Sur2-/- MEFs at an MOI of 0.05. Coinfection
      of Sur2-/- MEFs with wt MAV-1 and CR1Delta, CR2Delta, or CR3Delta mutant viruses
      rescued the defects of wt MAV-1 replication. This result suggests that an
      inhibiting effect on wt E1A protein expression and/or E1A function might account
      for the severe viral replication defect of MAV-1 in Sur2-/- MEFs at an MOI of
      0.05. Moreover, titrations of virus yields from infected brains of inbred strains
      of mice showed that E1A null and CR3Delta mutant viruses had a significant defect
      in virus replication compared to wt MAV-1. This result supports the hypothesis
      that the MAV-1 E1A-mSur2 interaction is important in MAV-1 replication in mice.

PMID- 15731222
TI  - Deletion of highly conserved arginine-rich RNA binding motif in cowpea chlorotic
      mottle virus capsid protein results in virion structural alterations and RNA
      packaging constraints.
AB  - The N-proximal region of cowpea chlorotic mottle virus (CCMV) capsid protein (CP)
      contains an arginine-rich RNA binding motif (ARM) that is also found in the CPs
      of other members of Bromoviridae and in other RNA binding proteins such as the
      Tat and Rev proteins of human immunodeficiency virus. To assess the critical role
      played by this motif during encapsidation, a variant of CCMV RNA3 (C3) precisely
      lacking the ARM region (C3/Delta919) of its CP gene was constructed. The biology
      and the competence of the matured CP derived in vivo from C3/Delta919 to assemble
      and package progeny RNA was examined in whole plants. Image analysis and computer
      assisted three-dimensional reconstruction of wild-type and mutant virions
      revealed that the CP subunits bearing the engineered deletion assembled into
      polymorphic virions with altered surface topology. Northern blot analysis of
      virion RNA from mutant progeny demonstrated that the engineered mutation down
      regulated packaging of all four viral RNAs; however, the packaging effect was
      more pronounced on genomic RNA1 and RNA2 than genomic RNA3 and its CP mRNA. In
      vitro assembly assays with mutant CP subunits and RNA transcripts demonstrated
      that the mutant CP is inherently not defective in packaging genomic RNA1 (53%)
      and RNA2 (54%), but their incorporation into virions was competitively inhibited
      by the presence of other viral RNAs. Northern blot analysis of RNA encapsidation
      in vivo of two distinct bromovirus RNA3 chimeras, constructed by exchanging CPs
      having the Delta919 deletion, demonstrated that the role of the conserved N
      terminal ARM in recognizing and packaging specific RNA is distinct for each
      virus.

PMID- 15731223
TI  - Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome
      coronavirus S protein induce neutralizing antibodies: implications for the
      development of vaccines and antiviral agents.
AB  - The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS
      CoV) interacts with cellular receptors to mediate membrane fusion, allowing viral
      entry into host cells; hence it is recognized as the primary target of
      neutralizing antibodies, and therefore knowledge of antigenic determinants that
      can elicit neutralizing antibodies could be beneficial for the development of a
      protective vaccine. Here, we expressed five different fragments of S, covering
      the entire ectodomain (amino acids 48 to 1192), as glutathione S-transferase
      fusion proteins in Escherichia coli and used the purified proteins to raise
      antibodies in rabbits. By Western blot analysis and immunoprecipitation
      experiments, we showed that all the antibodies are specific and highly sensitive
      to both the native and denatured forms of the full-length S protein expressed in
      virus-infected cells and transfected cells, respectively. Indirect
      immunofluorescence performed on fixed but unpermeabilized cells showed that these
      antibodies can recognize the mature form of S on the cell surface. All the
      antibodies were also able to detect the maturation of the 200-kDa form of S to
      the 210-kDa form by pulse-chase experiments. When the antibodies were tested for
      their ability to inhibit SARS-CoV propagation in Vero E6 culture, it was found
      that the anti-SDelta10 antibody, which was targeted to amino acid residues 1029
      to 1192 of S, which include heptad repeat 2, has strong neutralizing activities,
      suggesting that this region of S carries neutralizing epitopes and is very
      important for virus entry into cells.

PMID- 15731224
TI  - Recombinant herpes simplex virus type 1 (HSV-1) codelivering interleukin-12p35 as
      a molecular adjuvant enhances the protective immune response against ocular HSV-1
      challenge.
AB  - An important aspect of ocular herpes simplex virus type 1 (HSV-1) vaccine
      development is identification of an appropriate adjuvant capable of significantly
      reducing both virus replication in the eye and explant reactivation in trigeminal
      ganglia. We showed recently that a recombinant HSV-1 vaccine expressing
      interleukin-4 (IL-4) is more efficacious against ocular HSV-1 challenge than
      recombinant viruses expressing IL-2 or gamma interferon (IFN-gamma) (Y. Osorio
      and H. Ghiasi, J. Virol. 77:5774-5783, 2003). We have now constructed and
      compared recombinant HSV-1 viruses expressing IL-12p35 or IL-12p40 molecule with
      IL-4-expressing HSV-1 recombinant virus. BALB/c mice were immunized
      intraperitoneally with IL-12p35-, IL-12p40-, IL-12p35+IL-12p40-, or IL-4
      expressing recombinant HSV-1 viruses. Controls included mice immunized with
      parental virus and mice immunized with the avirulent strain KOS. The efficacy of
      each vaccine in protecting against ocular challenge with HSV-1 was assessed in
      terms of survival, eye disease, virus replication in the eye, and explant
      reactivation. Neutralizing antibody titers, T-cell responses, and expression of
      32 cytokines and chemokines were also evaluated. Mice immunized with recombinant
      HSV-1 expressing IL-12p35 exhibited the lowest virus replication in the eye, the
      most rapid virus clearance, and the lowest level of explant reactivation. The
      higher efficacy against ocular virus replication and explant reactivation
      correlated with higher neutralizing antibody titers, cytotoxic-T-lymphocyte
      activities, and IFN-gamma expression in recombinant HSV-1 expressing IL-12p35
      compared to other vaccines. Mice immunized with both IL-12p35 and IL-12p40 had
      lower neutralizing antibody responses than mice immunized with IL-12p35 alone.
      Our results confirm that recombinant virus vaccines expressing cytokine genes can
      enhance the overall protection against infection, with the IL-12p35 vaccine being
      the most efficacious of those tested. Collectively, the results support the
      potential use of IL-12p35 as a vaccine adjuvant, without the toxicity-associated
      concerns of IL-12.

PMID- 15731225
TI  - Genetic analysis of the human papillomavirus type 31 differentiation-dependent
      late promoter.
AB  - Human papillomaviruses infect stratifying squamous epithelia, causing benign and
      malignant lesions. Upon differentiation of the host keratinocyte, the virus
      undergoes a dramatic increase in both DNA replication and transcription from the
      late promoter, leading to expression of late genes and virion morphogenesis. In
      human papillomavirus type 31 (HPV31), the late promoter is designated p742 and
      includes multiple start sites embedded within the E7 gene. In this report, we
      mapped viral DNA elements that control transcriptional activity from p742.
      Enhancer elements in the viral upstream regulatory region positively regulate
      this promoter. The region containing the transcriptional start sites is
      dispensable for activity, and at least two separate elements in the E6/E7 region
      are capable of supporting transcription. Of these, we mapped one to a 150-bp
      region of the E7 open reading frame and designate it the core p742 promoter.
      Using GF109203X, an inhibitor of protein kinase C signaling, we show that p742
      activation is independent of viral genome amplification. Finally, we mapped
      elements in the region of p742 that confer responsiveness to differentiation and
      show that the upstream regulatory region does not contribute to the
      differentiation response of p742. These studies are an important step toward
      understanding the functioning and regulation of this multiple-start promoter.

PMID- 15731226
TI  - Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in
      patients with hepatitis B virus infection.
AB  - CD4+ CD25+ regulatory T cells have been shown to maintain peripheral tolerance
      against self and foreign antigens. In this study we analyzed the effect of
      circulating CD4+ CD25+ T cells on CD8+-T-cell responses of patients with chronic
      and resolved hepatitis B virus (HBV) infection. We demonstrated that circulating
      CD4+ CD25+ T cells modulate the function and expansion of HBV-specific CD8+ cells
      ex vivo in all patients, regardless of whether they have chronic or resolved HBV
      infection. The possible role of CD4+ CD25+ T cells in the pathogenesis of chronic
      HBV infection is not supported by these data. However, these results might have
      implications for optimizing future immunotherapeutic approaches to HBV treatment.

PMID- 15731227
TI  - Selection of resistance in protease inhibitor-experienced, human immunodeficiency
      virus type 1-infected subjects failing lopinavir- and ritonavir-based therapy:
      mutation patterns and baseline correlates.
AB  - The selection of in vivo resistance to lopinavir was characterized by analyzing
      the longitudinal isolates from 54 protease inhibitor-experienced subjects who
      either experienced incomplete virologic response or viral rebound subsequent to
      initial response while on treatment with lopinavir-ritonavir in Phase II and III
      studies. The evolution of incremental resistance to lopinavir (emergence of new
      mutation[s] and/or at least a twofold increase in phenotypic resistance compared
      to baseline isolates) was highly dependent on the baseline phenotype and
      genotype. Among the subjects demonstrating evolution of lopinavir resistance,
      mutations at positions 82, 54, and 46 in human immunodeficiency virus protease
      emerged frequently, suggesting that these mutations are important for conferring
      high-level resistance. Less common mutations, such as L33F, I50V, and V32I
      together with I47V/A, were also selected; however, new mutations at positions 84,
      90, and 71 were not observed. The emergence of incremental resistance contrasts
      greatly with the low incidence of resistance observed after initiating lopinavir
      ritonavir therapy in antiretroviral-naive patients, suggesting that partial
      resistance accumulated during prior protease inhibitor therapy can compromise the
      genetic barrier to resistance to lopinavir-ritonavir. The emergence of
      incremental resistance was uncommon in subjects whose baseline isolates contained
      eight or more mutations associated with lopinavir resistance and/or displayed >60
      fold-reduced susceptibility to lopinavir, providing insight into suitable upper
      genotypic and phenotypic breakpoints for lopinavir-ritonavir.

PMID- 15731228
TI  - Altered function in CD8+ T cells following paramyxovirus infection of the
      respiratory tract.
AB  - For many respiratory pathogens, CD8+ T cells have been shown to play a critical
      role in clearance. However, there are still many unanswered questions with regard
      to the factors that promote the most efficacious immune response and the
      potential for immunoregulation of effector cells at the local site of infection.
      We have used infection of the respiratory tract with the model paramyxovirus
      simian virus 5 (SV5) to study CD8+ T-cell responses in the lung. For the present
      study, we report that over time a population of nonresponsive, virus-specific
      CD8+ T cells emerged in the lung, culminating in a lack of function in
      approximately 85% of cells specific for the immunodominant epitope from the viral
      matrix (M) protein by day 40 postinfection. Concurrent with the induction of
      nonresponsiveness, virus-specific cells that retained function at later times
      postinfection exhibited an increased requirement for CD8 engagement. This change
      was coupled with a nearly complete loss of functional phosphoprotein-specific
      cells, a response previously shown to be almost exclusively CD8 independent.
      These studies add to the growing evidence for immune dysregulation following
      viral infection of the respiratory tract.

PMID- 15731229
TI  - Differential role for TLR3 in respiratory syncytial virus-induced chemokine
      expression.
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
      infection in young infants worldwide. Previous studies have reported that the
      induction of interleukin-8/CXCL8 and RANTES/CCL5 correlates with disease severity
      in humans. The production of these chemokines is elicited by viral replication
      and is NF-kappaB dependent. RSV, a negative-sense single-stranded RNA virus,
      requires full-length positive-sense RNA for synthesis of new viral RNA. The aim
      of our studies was to investigate whether active viral replication by RSV could
      evoke chemokine production through TLR3-mediated signaling pathways. In TLR3
      transfected HEK 293 cells, live RSV preferentially activated chemokines in both a
      time- and dose-dependent manner compared to vector controls. RSV was also shown
      to upregulate TLR3 in human lung fibroblasts and epithelial cells (MRC-5 and
      A549). Targeting the expression of TLR3 with small interfering RNA decreased
      synthesis of IP-10/CXCL10 and CCL5 but did not significantly reduce levels of
      CXCL8. Blocking the expression of the adapter protein MyD88 established a role
      for MyD88 in CXCL8 production, whereas CCL5 synthesis was found to be MyD88
      independent. Production of CCL5 by RSV was induced directly through TLR3
      signaling pathways and did not require interferon (IFN) signaling through the IFN
      alpha/beta receptor. TLR3 did not affect viral replication, since equivalent
      viral loads were recovered from RSV-infected cells despite altered TLR3
      expression. Taken together, our studies indicate that TLR3 mediates inflammatory
      cytokine and chemokine production in RSV-infected epithelial cells.

PMID- 15731230
TI  - Protection of rhesus monkeys against infection with minimally pathogenic simian
      human immunodeficiency virus: correlations with neutralizing antibodies and
      cytotoxic T cells.
AB  - We studied the capacity of active immunization of rhesus monkeys with HIV-1
      envelope protein (Env) to induce primary virus cross-reactive neutralizing
      antibodies to prevent infection following intravenous challenge with simian-human
      immunodeficiency virus (SHIV). Monkeys were immunized with the human
      immunodeficiency type 1 (HIV-1) strain R2 Env. Initially, the Env was expressed
      in vivo by an alphavirus replicon particle system, and then it was administered
      as soluble oligomeric gp140. Concurrently, groups of monkeys received expression
      vectors that encoded either simian immunodeficiency virus (SIV) gag/pol genes or
      no SIV genes in vivo to test the additional protective benefit of concurrent
      induction of virus-specific cell-mediated immune (CMI) responses. Groups of
      control monkeys received either the gag/pol regimen or sham immunizations. The
      antibodies induced by the Env immunization regimen neutralized diverse primary
      HIV-1 strains. Similarly, potent CMI responses were induced by the gag/pol
      regimen, as measured by gamma interferon enzyme-linked immunospot assays.
      Differences in the responses among groups of monkeys strongly suggested that
      there was interference between the Env and gag/pol immunization regimens.
      Complete protection of some of the monkeys against infection after intravenous
      challenge with the partially pathogenic SHIV(DH12R (Clone 7)) was associated
      independently with both neutralizing antibody and CMI responses. Protection was
      associated with SHIV(DH12 (Clone 7)) serum neutralizing antibody titers of > or
      =1:80 or with cellular immune responses corresponding to >2,000 spot forming
      cells per 10(6) peripheral blood mononuclear cells. Immunization was also
      associated with a reduction in the magnitude and duration of virus load.
      Induction of cross-reactive, primary HIV-1-neutralizing antibodies is feasible
      and, when potent, may result in complete protection against infection with a
      heterologous challenge virus strain.

PMID- 15731231
TI  - Increased epitope-specific CD8+ T cells prevent murine coronavirus spread to the
      spinal cord and subsequent demyelination.
AB  - CD8+ T cells are important for clearance of neurotropic mouse hepatitis virus
      (MHV) strain A59, although their possible role in A59-induced demyelination is
      not well understood. We developed an adoptive-transfer model to more clearly
      elucidate the role of virus-specific CD8+ T cells during the acute and chronic
      phases of infection with A59 that is described as follows. C57BL/6 mice were
      infected with a recombinant A59 virus expressing the gp33 epitope, an H-2Db
      restricted CD8+ T-cell epitope encoded in the glycoprotein of lymphocytic
      choriomeningitis virus, as a fusion with the enhanced green fluorescent protein
      (RA59-gfp/gp33). P14 splenocytes (transgenic for a T-cell receptor specific for
      the gp33 epitope) were transferred at different times pre- and postinfection
      (p.i.). Adoptive transfer of P14 splenocytes 1 day prior to infection with RA59
      gfp/gp33, but not control virus lacking the gp33 epitope, RA59-gfp, reduced
      weight loss and viral replication and spread in the brain and to the spinal cord.
      Furthermore, demyelination was significantly reduced compared to that in
      nonrecipients. However, when P14 cells were transferred on day 3 or 5 p.i., no
      difference in acute or chronic disease was observed compared to that in
      nonrecipients. Protection in mice receiving P14 splenocytes prior to infection
      correlated with a robust gp33-specific immune response that was not observed in
      mice receiving the later transfers. Thus, an early robust CD8+ T-cell response
      was necessary to reduce virus replication and spread, specifically to the spinal
      cord, which protected against demyelination in the chronic phase of the disease.

PMID- 15731232
TI  - Identification of sites in adenovirus hexon for foreign peptide incorporation.
AB  - Adenovirus type 5 (Ad5) is one of the most promising vectors for gene therapy
      applications. Genetic engineering of Ad5 capsid proteins has been employed to
      redirect vector tropism, to enhance infectivity, or to circumvent preexisting
      host immunity. As the most abundant capsid protein, hexon modification is
      particularly attractive. However, genetic modification of hexon often results in
      failure of rescuing viable viruses. Since hypervariable regions (HVRs) are
      nonconserved among hexons of different serotypes, we investigated whether the
      HVRs could be used for genetic modification of hexon by incorporating
      oligonucleotides encoding six histidine residues (His6) into different HVRs in
      the Ad5 genome. The modified viruses were successfully rescued, and the yields of
      viral production were similar to that of unmodified Ad5. A thermostability assay
      suggested the modified viruses were stable. The His6 epitopes were expressed in
      all modified hexon proteins as assessed by Western blotting assay, although the
      intensity of the reactive bands varied. In addition, we examined the binding
      activity of anti-His tag antibody to the intact virions with the enzyme-linked
      immunosorbent assay and found the His6 epitopes incorporated in HVR2 and HVR5
      could bind to anti-His tag antibody. This suggested the His6 epitopes in HVR2 and
      HVR5 were exposed on virion surfaces. Finally, we examined the infectivities of
      the modified Ad vectors. The His6 epitopes did not affect the native infectivity
      of Ad5 vectors. In addition, the His6 epitopes did not appear to mediate His6
      dependent viral infection, as assessed in two His6 artificial receptor systems.
      Our study provided valuable information for studies involving hexon modification.

PMID- 15731233
TI  - Single-amino-acid substitutions in open reading frame (ORF) 1b-nsp14 and ORF 2a
      proteins of the coronavirus mouse hepatitis virus are attenuating in mice.
AB  - A reverse genetic system was recently established for the coronavirus mouse
      hepatitis virus strain A59 (MHV-A59), in which cDNA fragments of the RNA genome
      are assembled in vitro into a full-length genome cDNA, followed by
      electroporation of in vitro-transcribed genome RNA into cells with recovery of
      viable virus. The "in vitro-assembled" wild-type MHV-A59 virus (icMHV-A59)
      demonstrated replication identical to laboratory strains of MHV-A59 in tissue
      culture; however, icMHV-A59 was avirulent following intracranial inoculation of
      C57BL/6 mice. Sequencing of the cloned genome cDNA fragments identified two
      single-nucleotide mutations in cloned genome fragment F, encoding a Tyr6398His
      substitution in open reading frame (ORF) 1b p59-nsp14 and a Leu94Pro substitution
      in the ORF 2a 30-kDa protein. The mutations were repaired individually and
      together in recombinant viruses, all of which demonstrated wild-type replication
      in tissue culture. Following intracranial inoculation of mice, the viruses
      encoding Tyr6398His/Leu94Pro substitutions and the Tyr6398His substitution alone
      demonstrated log10 50% lethal dose (LD50) values too great to be measured. The
      Leu94Pro mutant virus had reduced but measurable log10 LD5), and the "corrected"
      Tyr6398/Leu94 virus had a log10 LD50 identical to wild-type MHV-A59. The
      experiments have defined residues in ORF 1b and ORF 2a that attenuate virus
      replication and virulence in mice but do not affect in vitro replication. The
      results suggest that these proteins serve roles in pathogenesis or virus survival
      in vivo distinct from functions in virus replication. The study also demonstrates
      the usefulness of the reverse genetic system to confirm the role of residues or
      proteins in coronavirus replication and pathogenesis.

PMID- 15731234
TI  - B-cell responses in patients who have recovered from severe acute respiratory
      syndrome target a dominant site in the S2 domain of the surface spike
      glycoprotein.
AB  - Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease
      caused by a novel strain of coronavirus. Examination of the immune responses of
      patients who have recovered from SARS should provide important information for
      design of a safe and effective vaccine. We determined the continuous viral
      epitopes targeted by antibodies in plasma samples from convalescent SARS patients
      through biopanning with a vast M13 phage display dodecapeptide library. These
      epitopes converged to very short peptide fragments, one on each of the structural
      proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3.
      Immunoassays found that most of the patients who had recovered from SARS
      developed complementary antibodies to the epitope-rich region on the spike S2
      protein, indicating that this is an immunodominant site on the viral envelope
      comprising the spike, matrix, and small envelope glycoproteins. These S2
      targeting antibodies were shown to effectively neutralize the coronavirus,
      indicating that they provided protective immunity to help the patients recover
      from the viral infection. These results suggest that the SARS coronavirus might
      have an antigenic profile distinct from those of other human or animal
      coronaviruses. Due to the tested safety and protective effects of the
      convalescent-phase serological antibodies, identification of their complementary
      antigens may enable the design of an epitope-based vaccine to prevent potential
      antibody-mediated immunopathology.

PMID- 15731235
TI  - Architecture of replication compartments formed during Epstein-Barr virus lytic
      replication.
AB  - Epstein-Barr virus (EBV) productive DNA replication occurs at discrete sites,
      called replication compartments, in nuclei. In this study we performed
      comprehensive analyses of the architecture of the replication compartments. The
      BZLF1 oriLyt binding proteins showed a fine, diffuse pattern of distribution
      throughout the nuclei at immediate-early stages of induction and then became
      associated with the replicating EBV genome in the replication compartments during
      lytic infection. The BMRF1 polymerase (Pol) processivity factor showed a
      homogenous, not dot-like, distribution in the replication compartments, which
      completely coincided with the newly synthesized viral DNA. Inhibition of viral
      DNA replication with phosphonoacetic acid, a viral DNA Pol inhibitor, eliminated
      the DNA-bound form of the BMRF1 protein, although the protein was sufficiently
      expressed in the cells. These observations together with the findings that almost
      all abundantly expressed BMRF1 proteins existed in the DNA-bound form suggest
      that the BMRF1 proteins not only act at viral replication forks as Pol processive
      factors but also widely distribute on newly replicated EBV genomic DNA. In
      contrast, the BALF5 Pol catalytic protein, the BALF2 single-stranded-DNA binding
      protein, and the BBLF2/3 protein, a component of the helicase-primase complex,
      were colocalized as distinct dots distributed within replication compartments,
      representing viral replication factories. Whereas cellular replication factories
      are constructed based on nonchromatin nuclear structures and nuclear matrix,
      viral replication factories were easily solubilized by DNase I treatment. Thus,
      compared with cellular DNA replication, EBV lytic DNA replication factories would
      be simpler so that construction of the replication domain would be more relaxed.

PMID- 15731236
TI  - A noninfectious simian/human immunodeficiency virus DNA vaccine that protects
      macaques against AIDS.
AB  - Simian/human immunodeficiency virus SHIV(KU2) replicates with extremely high
      titers in macaques. In order to determine whether the DNA of the viral genome
      could be used as a vaccine if the DNA were rendered noninfectious, we deleted the
      reverse transcriptase gene from SHIVKU2 and inserted this DNA (DeltartSHIVKU2)
      into a plasmid that was then used to test gene expression and immunogenicity.
      Transfection of Jurkat and human embryonic kidney epithelial (HEK 293) cells with
      the DNA resulted in production of all of the major viral proteins and their
      precursors and transient export of a large quantity of the Gag p27 into the
      supernatant fluid. As expected, no infectious virus was produced in these
      cultures. Four macaques were injected intradermally with 2 mg of the DNA at 0, 8,
      and 18 weeks. The animals developed neutralizing antibodies and low enzyme-linked
      immunospot assay (E-SPOT) titers against SHIVKU2. These four animals and two
      unvaccinated control animals were then challenged with heterologous SHIV89.6P
      administered into their rectums. The two control animals developed viral RNA
      titers exceeding 10(6) copies/ml of plasma, and these titers were accompanied by
      the loss of CD4+ T cells by 2 weeks after challenge. The two control animals died
      at weeks 8 and 16, respectively. All four of the immunized animals became
      infected with the challenge virus but developed lower titers of viral RNA in
      plasma than the control animals, and the titers decreased over time in three of
      the four macaques. The fourth animal remained viremic and died at week 47.
      Whereas the control animals failed to develop E-SPOT responses, all four of the
      immunized animals developed anamnestic E-SPOT responses after challenge. The
      animal that died developed the highest E-SPOT response and was the only one that
      produced neutralizing antibodies against the challenge virus. These results
      established that noninfectious DNA of pathogenic SHIV could be used as a vaccine
      to prevent AIDS, even though the immunological assays used did not predict the
      manner in which the challenge virus would replicate in the vaccinated animals.

PMID- 15731237
TI  - Systematic pathogenesis and replication of avian hepatitis E virus in specific
      pathogen-free adult chickens.
AB  - Hepatitis E virus (HEV) is an important human pathogen. Due to the lack of a cell
      culture system and a practical animal model for HEV, little is known about its
      pathogenesis and replication. The discovery of a strain of HEV in chickens,
      designated avian HEV, prompted us to evaluate chickens as a model for the study
      of HEV. Eighty-five 60-week-old specific-pathogen-free chickens were randomly
      divided into three groups. Group 1 chickens (n=28) were each inoculated with 5 x
      10(4.5) 50% chicken infectious doses of avian HEV by the oronasal route, group 2
      chickens (n=29) were each inoculated with the same dose by the intravenous (i.v.)
      route, and group 3 chickens (n=28) were not inoculated and were used as controls.
      Two chickens from each group were necropsied at 1, 3, 5, 7, 10, 13, 16, 20, 24,
      28, 35, and 42 days postinoculation (dpi), and the remaining chickens were
      necropsied at 56 dpi. Serum, fecal, and various tissue samples, including liver
      and spleen samples, were collected at each necropsy for pathological and
      virological testing. By 21 dpi, all oronasally and i.v. inoculated chickens had
      seroconverted. Fecal virus shedding was detected variably from 1 to 20 dpi for
      the i.v. group and from 10 to 56 dpi for the oronasal group. Avian HEV RNA was
      detected in serum, bile, and liver samples from both i.v. and oronasally
      inoculated chickens. Gross liver lesions, characterized by subcapsular
      hemorrhages or enlargement of the right intermediate lobe, were observed in 7 of
      28 oronasally and 7 of 29 i.v. inoculated chickens. Microscopic liver lesions
      were mainly lymphocytic periphlebitis and phlebitis. The lesion scores were
      higher for oronasal (P=0.0008) and i.v. (P=0.0029) group birds than for control
      birds. Slight elevations of the plasma liver enzyme lactate dehydrogenase were
      observed in infected chickens. The results indicated that chickens are a useful
      model for studying HEV replication and pathogenesis. This is the first report of
      HEV transmission via its natural route in a homologous animal model.

PMID- 15731238
TI  - Characterization of an in vitro model of alphavirus infection of immature and
      mature neurons.
AB  - Terminally differentiated, mature neurons are essential cells that are not easily
      regenerated. Neurotropic viruses, such as Sindbis virus (SV), cause
      encephalomyelitis through their ability to replicate in neurons. SV causes the
      death of immature neurons, while mature neurons can often survive infection. The
      lack of a reproducible and convenient neuronal cell culture system has hindered a
      detailed study of the differences in levels of virus replication between immature
      and mature neurons and the molecular events involved in virus clearance from
      mature neurons. We have characterized SV replication in immortalized CSM14.1 rat
      neuronal cells that can be differentiated into neurons. During differentiation,
      CSM14.1 cells ceased dividing, developed neuronal morphology, and expressed
      neuron-specific cell markers. SV infection of undifferentiated CSM14.1 cells was
      efficient and resulted in high levels of virus replication and cell death. SV
      infection of differentiated CSM14.1 cells was less efficient and resulted in the
      production of 10- to 100-fold less virus and cell survival. In undifferentiated
      cells, SV induced a rapid shutdown of cellular protein synthesis and pE2 was
      efficiently processed to E2 (ratio of E2 to pE2, 2.14). In differentiated cells,
      the SV-induced shutdown of cellular protein synthesis was transient and pE2 was
      the primary form of E2 in cells (ratio of E2 to pE2, 0.0426). We conclude that
      age-dependent restriction of virus replication is an intrinsic property of
      maturing neurons and that the CSM14.1 cell line is a convenient model system for
      investigating the interactions of alphaviruses with neurons at various stages of
      differentiation.

PMID- 15731239
TI  - Nuclear localization of Japanese encephalitis virus core protein enhances viral
      replication.
AB  - Japanese encephalitis virus (JEV) core protein was detected in both the nucleoli
      and cytoplasm of mammalian and insect cell lines infected with JEV or transfected
      with the expression plasmid of the core protein. Mutation analysis revealed that
      Gly(42) and Pro(43) in the core protein are essential for the nuclear and
      nucleolar localization. A mutant M4243 virus in which both Gly(42) and Pro(43)
      were replaced by Ala was recovered by plasmid-based reverse genetics. In C6/36
      mosquito cells, the M4243 virus exhibited RNA replication and protein synthesis
      comparable to wild-type JEV, whereas propagation in Vero cells was impaired. The
      mutant core protein was detected in the cytoplasm but not in the nucleus of
      either C6/36 or Vero cell lines infected with the M4243 virus. The impaired
      propagation of M4243 in mammalian cells was recovered by the expression of wild
      type core protein in trans but not by that of the mutant core protein. Although
      M4243 mutant virus exhibited a high level of neurovirulence comparable to wild
      type JEV in spite of the approximately 100-fold-lower viral propagation after
      intracerebral inoculation to 3-week-old mice of strain Jcl:ICR, no virus was
      recovered from the brain after intraperitoneal inoculation of the mutant. These
      results indicate that nuclear localization of JEV core protein plays crucial
      roles not only in the replication in mammalian cells in vitro but also in the
      pathogenesis of encephalitis induced by JEV in vivo.

PMID- 15731240
TI  - Glycoprotein M is an essential lytic replication protein of the murine
      gammaherpesvirus 68.
AB  - All herpesviruses encode a homolog of glycoprotein M (gM), which appears to
      function in virion morphogenesis. Despite its conservation, gM is inessential for
      the lytic replication of alphaherpesviruses. In order to address the importance
      of gM in gammaherpesviruses, we disrupted it in the murine gammaherpesvirus 68
      (MHV-68). The mutant virus completely failed to propagate in normally permissive
      fibroblasts. The defective genome was rescued by either homologous recombination
      to restore the wild-type gM in situ or the insertion of an ectopic, intergenic
      expression cassette encoding gM into the viral genome. Thus, gM was essential for
      the lytic replication of MHV-68.

PMID- 15731241
TI  - Kaposi's sarcoma-associated herpesvirus reactivation is regulated by interaction
      of latency-associated nuclear antigen with recombination signal sequence-binding
      protein Jkappa, the major downstream effector of the Notch signaling pathway.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor
      contributing to development of Kaposi's sarcoma. KSHV establishes a latent
      infection in human B cells expressing the latency-associated nuclear antigen
      (LANA), a critical factor in the regulation of viral latency. LANA controls KSHV
      latent infection through repression of RTA, an activator of many lytic promoters.
      RTA activates the expression of several lytic viral genes by interacting with
      recombination signal sequence-binding protein Jkappa (RBP-Jkappa), a
      transcriptional repressor and the target of the Notch signaling pathway. The
      recognition that a number of KSHV lytic gene promoters, including RTA, contain
      RBP-Jkappa binding sites raised the possibility that RBP-Jkappa-mediated
      repression may be central to the establishment of latency. Here, we tested this
      hypothesis by examining the regulation of RTA by LANA through binding to RBP
      Jkappa. This study demonstrates that LANA physically associates with RBP-Jkappa
      in vitro and in KSHV-infected cells, with the complex formed capable of binding
      to RBP-Jkappa cognate sequences. RBP-Jkappa binding sites within the RTA promoter
      have been found to be critical for LANA-mediated repression. Our study describes
      a novel mechanism through which LANA maintains KSHV latency by targeting a major
      downstream effector of the Notch signaling pathway.

PMID- 15731242
TI  - A Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50 deletion
      mutant is defective for reactivation of latent virus and DNA replication.
AB  - Kaposi's sarcoma-associated herpesvirus (also called human herpesvirus type 8
      [HHV8]) latently infects a number of cell types. Reactivation of latent virus can
      occur by treatment with the phorbol ester tetradecanoyl phorbol acetate (TPA) or
      with the transfection of plasmids expressing the lytic switch activator protein K
      Rta, the gene product of ORF50. K-Rta expression is sufficient for the activation
      of the entire lytic cycle and the transactivation of viral genes necessary for
      DNA replication. In addition, recent evidence has suggested that K-Rta may
      participate directly in the initiation of lytic DNA synthesis. We have now
      generated a recombinant HHV8 bacterial artificial chromosome (BAC) with a large
      deletion within the ORF50 locus. This BAC, BAC36Delta50, failed to produce
      infectious virus upon treatment with TPA and was defective for DNA synthesis.
      Expression of K-Rta in trans in BAC36Delta50-containing cells was able to abolish
      both defects. Real-time PCR revealed that K-bZIP, ORF40/41, and K8.1 were not
      expressed when BAC36Delta50-containing cells were induced with TPA. However, the
      mRNA levels of ORF57 were over fivefold higher in TPA-treated BAC36Delta50
      containing cells than those observed in similarly treated wild-type BAC
      containing cells. In addition, immunohistochemical analysis showed that while the
      latency-associated nuclear antigen (LANA) was expressed in the mutant BAC
      containing cells, ORF59 and K8.1 expression was not detected in TPA-induced
      BAC36Delta50-containing cells. These results showed that K-Rta is essential for
      lytic viral reactivation and transactivation of viral genes contributing to DNA
      replication.

PMID- 15731243
TI  - Receptor-induced conformational changes in the SU subunit of the avian
      sarcoma/leukosis virus A envelope protein: implications for fusion activation.
AB  - The avian sarcoma/leukosis virus (ASLV) is activated for fusion by a two-step
      mechanism. For ASLV subgroup A (ASLV-A), association with its receptor (Tva) at
      neutral pH converts virions to a form that can bind target membranes and, in some
      assays, induce the lipid-mixing stage of fusion. Low pH is necessary to complete
      the fusion reaction. ASLV-A env (EnvA) exists on the viral surface as a trimer of
      heterodimers consisting of receptor binding (SU-A) and fusion-mediating (TM-A)
      subunits. As the receptor binding and fusion-mediating functions reside in
      separate subunits, we hypothesize that SU-A and TM-A are conformationally
      coupled. To begin to understand the effect of the binding of a soluble 47-residue
      domain of the receptor (sTva) on this coupling and the subsequent function of low
      pH, we prepared recombinant proteins representing full-length SU-A and a nested
      set of deletion mutant proteins. Full-length SU-A binds sTva with high affinity,
      but even small deletions at either the N or the C terminus severely impair sTva
      binding. We have purified the full-length SU-A subunit and characterized its
      interactions with sTva and the subsequent effect of low pH on the complex. sTva
      binds SU-A with an apparent KD of 3 pM. Complex formation occludes hydrophobic
      surfaces and tryptophan residues and leads to a partial loss of alpha-helical
      structure in SU-A. Low pH does not alter the off rate for the complex, further
      alter the secondary structure of SU-A, or induce measurable changes in tryptophan
      environment. The implications of these findings for fusion are discussed.

PMID- 15731244
TI  - Stoichiometry of antibody neutralization of human immunodeficiency virus type 1.
AB  - The human immunodeficiency virus envelope glycoproteins function as trimers on
      the viral surface, where they are targeted by neutralizing antibodies. Different
      monoclonal antibodies neutralize human immunodeficiency virus type 1 (HIV-1)
      infectivity by binding to structurally and functionally distinct moieties on the
      envelope glycoprotein trimer. By measuring antibody neutralization of viruses
      with mixtures of neutralization-sensitive and neutralization-resistant envelope
      glycoproteins, we demonstrate that the HIV-1 envelope glycoprotein trimer is
      inactivated by the binding of a single antibody molecule. Virus neutralization
      requires essentially all of the functional trimers to be occupied by at least one
      antibody. This model applies to antibodies differing in neutralizing potency and
      to virus isolates with various neutralization sensitivities. Understanding these
      requirements for HIV-1 neutralization by antibodies will assist in establishing
      goals for an effective AIDS vaccine.

PMID- 15731245
TI  - The cytokine osteopontin modulates the severity of rotavirus diarrhea.
AB  - Osteopontin (OPN) is a sialated phosphoprotein found in tissues and secreted into
      body fluids. It is an integrin ligand with pleiotropic functions as an
      extracellular matrix protein in mineralized tissues and a cytokine that is active
      in cell signaling (A. B. Tuck, C. Hota, S. M. Wilson, and A. F. Chambers,
      Oncogene 22:1198-1205, 2003). To determine whether OPN may be important in
      mucosal defense against viral pathogens, we evaluated the OPN response to
      rotavirus infection and the extent of diarrhea manifested by infected opn null
      mutant (opn-/-) mice. Reverse transcription-PCR, Northern and Western blots, and
      immunohistochemical studies of the HT-29 intestinal epithelial cell line and
      murine intestine were used to evaluate OPN mRNA and product. Intestinal closed
      loops and diarrheal observations determined disease severity and duration. OPN
      mRNA levels increased after infection of HT-29 cells, peaking in 4 to 6 h.
      Infected cultures contained 925 microg of OPN/ml, while for controls the levels
      were below detection (50 microg/ml). Infection increased OPN mRNA levels in
      intestinal tissue between 2 and 24 h postinoculation and increased OPN protein in
      intestinal fluid. The cellular localization of OPN was supranuclear and apical,
      and responding cells were diffusely distributed on the villus surface. Three days
      after infection, closed intestinal loops from opn-/- mice contained more fluid
      than loops from controls, although secretion levels at the onset of illness were
      similar. Null mutant mice experienced more intense and prolonged diarrhea than
      controls. Rotavirus infection of intestinal epithelial cells and murine intestine
      caused marked increases in OPN mRNA levels and secreted OPN protein. OPN
      deficient mice suffered prolonged disease.

PMID- 15731246
TI  - B1 lymphocytes and myeloid dendritic cells in lymphoid organs are preferential
      extratumoral sites of parvovirus minute virus of mice prototype strain
      expression.
AB  - Due to their oncolytic properties and apathogenicity, autonomous parvoviruses
      have attracted significant interest as possible anticancer agents. Recent
      preclinical studies provided evidence of the therapeutic potential of minute
      virus of mice prototype strain (MVMp) and its recombinant derivatives. In a
      murine model of hemangiosarcoma, positive therapeutic outcome correlated with
      high intratumoral expression of MVMp-encoded genes in tumors and lymphoid organs,
      especially in tumor-draining lymph nodes. The source and relevance of this
      extratumoral expression, which came as a surprise because of the known
      fibrotropism of MVMp, remained unclear. In the present study, we investigated (i)
      whether the observed expression pattern occurs in different tumor models, (ii)
      which cell population is targeted by the virus, and (iii) the immunological
      consequences of this infection. Significant MVMp gene expression was detected in
      lymphoid tissues from infected tumor-free as well as melanoma-, lymphoma-, and
      hemangiosarcoma-bearing mice. This expression was especially marked in lymph
      nodes draining virus-injected tumors. Fluorescent in situ hybridization analysis,
      multicolor fluorescence-activated cell sorting, and quantitative reverse
      transcription-PCR revealed that MVMp was expressed in rare subpopulations of
      CD11b (Mac1)-positive cells displaying CD11c+ (myeloid dendritic cells [MDC]) or
      CD45B (B220+ [B1 lymphocytes]) markers. Apart from the late deletion of cytotoxic
      memory cells (CD8+ CD44+ CD62L-), this infection did not lead to significant
      alteration of the immunological profile of cells populating lymphoid organs.
      However, subtle changes were detected in the production of specific
      proinflammatory cytokines in lymph nodes from virus-treated animals. Considering
      the role of B1 lymphocytes and MDC in cancer and immunological surveillance, the
      specific ability of these cell types to sustain parvovirus-driven gene expression
      may be exploited in gene therapy protocols.

PMID- 15731247
TI  - Complex formation among murine cytomegalovirus US22 proteins encoded by genes
      M139, M140, and M141.
AB  - The murine cytomegalovirus (MCMV) proteins encoded by US22 genes M139, M140, and
      M141 function, at least in part, to regulate replication of this virus in
      macrophages. Mutant MCMV having one or more of these genes deleted replicates
      poorly in macrophages in culture and in the macrophage-dense environment of the
      spleen. In this report, we demonstrate the existence of stable complexes formed
      by the products of all three of these US22 genes, as well as a complex composed
      of the products of M140 and M141. These complexes form in the absence of other
      viral proteins; however, the pM140/pM141 complex serves as a requisite binding
      partner for the M139 gene products. Products from all three genes colocalize to a
      perinuclear region of the cell juxtaposed to or within the cis-Golgi region but
      excluded from the trans-Golgi region. Interestingly, expression of pM141
      redirects pM140 from its predominantly nuclear residence to the perinuclear,
      cytoplasmic locale where these US22 proteins apparently exist in complex. Thus,
      complexing of these nonessential, early MCMV proteins likely confers a
      function(s) independent of each individual protein and important for optimal
      replication of MCMV in its natural host.

PMID- 15731248
TI  - Increased multinucleoside drug resistance and decreased replicative capacity of a
      human immunodeficiency virus type 1 variant with an 8-amino-Acid insert in the
      reverse transcriptase.
AB  - Resistance to antiretroviral drugs is generally conferred by specific amino acid
      substitutions, rather than insertions or deletions, in reverse transcriptase (RT)
      of human immunodeficiency virus type 1 (HIV-1). The exception to these findings
      is the amino acid insertions found in the beta3-beta4 loop of the RT enzyme in
      response to treatment with nucleoside reverse transcriptase inhibitors. This
      insert consists most commonly of two amino acids, but we describe in detail the
      evolution of a variant with an 8-amino-acid (aa) insert in a patient treated with
      zidovudine (ZDV) and 2'-3'-dideoxycytidine (ddC). The 24-nucleotide insert is a
      partial duplication of local sequences but also contains a sequence segment of
      unknown origin. Extensive sequence analysis of longitudinal patient samples
      indicated that the HIV-1 population prior to the start of therapy contained not
      the wild-type amino acid 215T in RT but a mixture with 215D and 215C. Treatment
      with ZDV and subsequent ZDV-ddC combination therapy resulted in the evolution of
      an HIV-1 variant with a typical ZDV resistance genotype (41L, 44D, 67N, 69D,
      210W, 215Y), which was slowly replaced by the insert-containing variant (41L,
      44D, insert at position 69, 70R, 210W, 215Y). The latter variant demonstrated
      increased resistance to a wide range of drugs, indicating that the 8-aa insert
      augments nucleoside analogue resistance. The gain in drug resistance of the
      insert variant came at the expense of a reduction in replication capacity when
      assayed in the absence of drugs. We compared these data with the resistance and
      replication properties of 133 insert-containing sequences of different
      individuals present in the ViroLogic database and found that the size and actual
      sequence of the insert at position 69 influence the level of resistance to
      nucleoside analogues.

PMID- 15731249
TI  - Stable secondary structure near the nicking site for adeno-associated virus type
      2 Rep proteins on human chromosome 19.
AB  - Adeno-associated virus serotype 2 (AAV-2) can preferentially integrate its DNA
      into a 4-kb region of human chromosome 19, designated AAVS1. The nicking activity
      of AAV-2's Rep68 or Rep78 proteins is essential for preferential integration.
      These proteins nick at the viral origin of DNA replication and at a similar site
      within AAVS1. The current nicking model suggests that the strand containing the
      nicking site is separated from its complementary strand prior to nicking. In AAV
      serotypes 1 through 6, the nicking site is flanked by a sequence that is
      predicted to form a stem-loop with standard Watson-Crick base pairing. The region
      flanking the nicking site in AAVS1 (5'-GGCGGCGGT/TGGGGCTCG-3' [the slash
      indicates the nicking site]) lacks extensive potential for Watson-Crick base
      pairing. We therefore performed an empirical search for a stable secondary
      structure. By comparing the migration of radiolabeled oligonucleotides containing
      wild-type or mutated sequences from the AAVS1 nicking site to appropriate
      standards, on native and denaturing polyacrylamide gels, we have found evidence
      that this region forms a stable secondary structure. Further confirmation was
      provided by circular dichroism analyses. We identified six bases that appear to
      be important in forming this putative secondary structure. Mutation of five of
      these bases, within the context of a double-stranded nicking substrate, reduces
      the ability of the substrate to be nicked by Rep78 in vitro. Four of these five
      bases are outside the previously recognized GTTGG nicking site motif and include
      parts of the CTC motif that has been demonstrated to be important for integration
      targeting.

PMID- 15731250
TI  - Importin-alpha promotes passage through the nuclear pore complex of human
      immunodeficiency virus type 1 Vpr.
AB  - Viral protein R (Vpr) of human immunodeficiency virus type 1 has potent
      karyophilic properties, but details of the mechanism by which it enters the
      nucleus remain to be clarified. We reported previously that two regions, located
      between residues 17 and 34 (alphaH1) and between residues 46 and 74 (alphaH2),
      are indispensable for the nuclear localization of Vpr. Here, we reveal that a
      chimeric protein composed of the nuclear localization signal of Vpr, glutathione
      S-transferase, and green fluorescent protein was localized at the nuclear
      envelope and then entered the nucleus upon addition of importin-alpha. An in
      vitro transport assay using a series of derivatives of importin-alpha
      demonstrated that the carboxyl terminus was required for this nuclear import
      process. We also showed that Vpr interacts with importin-alpha through alphaH1
      and alphaH2; only the interaction via alphaH1 is indispensable for the nuclear
      entry of Vpr. These observations indicate that importin-alpha functions as a
      mediator for the nuclear entry of Vpr.

PMID- 15731251
TI  - 3'-Terminal sequence in poliovirus negative-strand templates is the primary cis
      acting element required for VPgpUpU-primed positive-strand initiation.
AB  - The 5' cloverleaf in poliovirus RNA has a direct role in regulating the
      stability, translation, and replication of viral RNA. In this study, we
      investigated the role of stem a in the 5' cloverleaf in regulating the stability
      and replication of poliovirus RNA in HeLa S10 translation-replication reactions.
      Our results showed that disrupting the duplex structure of stem a destabilized
      viral RNA and inhibited efficient negative-strand synthesis. Surprisingly, the
      duplex structure of stem a was not required for positive-strand synthesis. In
      contrast, altering the primary sequence at the 5'-terminal end of stem a had
      little or no effect on negative-strand synthesis but dramatically reduced
      positive-strand initiation and the formation of infectious virus. The inhibition
      of positive-strand synthesis observed in these reactions was most likely a
      consequence of nucleotide alterations in the conserved sequence at the 3' ends of
      negative-strand RNA templates. Previous studies suggested that VPgpUpU
      synthesized on the cre(2C) hairpin was required for positive-strand synthesis.
      Therefore, these results are consistent with a model in which preformed VPgpUpU
      serves as the primer for positive-strand initiation on the 3'AAUUUUGUC5' sequence
      at the 3' ends of negative-strand templates. Our results suggest that this
      sequence is the primary cis-acting element that is required for efficient VPgpUpU
      primed positive-strand initiation.

PMID- 15731252
TI  - Biological differences between vesicular stomatitis virus Indiana and New Jersey
      serotype glycoproteins: identification of amino acid residues modulating pH
      dependent infectivity.
AB  - We previously generated recombinant vesicular stomatitis viruses (VSV) based on
      the Indiana serotype genome which contained either the homologous glycoprotein
      gene from the Indiana serotype (VSIV-GI) or the heterologous glycoprotein gene
      from the New Jersey serotype (VSIV-GNJ). The virus expressing the GNJ gene was
      more pathogenic than the parental VSIV-GI virus in swine, a natural host (26).
      For the present study, we investigated the biological differences between the GI
      and GNJ proteins that may be related to the differences in pathogenesis between
      VSIV-GI and VSIV-GNJ. We show that the capacities of viruses with either the GNJ
      or GI glycoprotein to infect cultured cells differ depending on the pH. VSIV-GNJ
      could infect cells at acidic pHs, while the infectivity of VSIV-GI was severely
      reduced. VSIV-GNJ infection was also more sensitive to inhibition by ammonium
      chloride, indicating that the GNJ protein had a lower pH threshold for membrane
      fusion. We applied selective pressure to VSIV-GI by growing it at successively
      lower pH values and isolated variant viruses in which we identified amino acid
      changes that conferred low-pH-resistant infectivity. Repeated passage in cell
      culture at pH 6.8 resulted in the selection of a VSIV-GI variant (VSIV-6.8) that
      was similar to VSIV-GNJ regarding its pH- and ammonium chloride-dependent
      infectivity. Sequence analysis of VSIV-6.8 revealed that it had a single amino
      acid substitution in the amino-terminal region of the glycoprotein (F18L). This
      alteration was shown to be responsible for the observed phenotype by site
      directed mutagenesis of a VSIV-GI full-length cDNA and analysis of the recovered
      engineered virus. A further adaptation of VSIV-6.8 to pHs 6.6 and 6.4 resulted in
      additional amino acid substitutions in areas of the glycoprotein that were not
      previously implicated in attachment or fusion.

PMID- 15731253
TI  - Role of the conserved nucleotide mismatch within 3'- and 5'-terminal regions of
      Bunyamwera virus in signaling transcription.
AB  - Bunyamwera virus (BUNV) is the prototype of the Bunyaviridae family of tri
      partite negative-sense RNA viruses. The three BUNV segments possess 3' and 5'
      nontranslated regions (NTRs) that signal two RNA synthesis activities: (i)
      transcription to generate mRNAs and (ii) replication to generate antigenomes that
      are replicated to yield further genomes. While the genome acts as a template for
      synthesis of both transcription and replication products, the antigenome allows
      synthesis of only replication products, with mRNAs being undetectable. Here, we
      investigate the basis for the fundamentally different signaling abilities of
      genomic and antigenomic strands. We show that the identity of only nucleotide
      position 9 within the genomic 3' NTR is critical for the different RNA synthesis
      characteristics of genomic and antigenomic strands, thus identifying this
      nucleotide as an essential component of the transcription promoter. This
      nucleotide is distinctive, as it interrupts an unbroken run of conserved
      complementary nucleotides within the 3' and 5' NTRs of all three segments. Our
      results show that the conserved mismatched arrangement of this nucleotide plays
      no detectable role in signaling transcription. Instead, we show that the
      transcription-signaling ability of this position is entirely dependent on its
      nucleotide identity. We further show that while a U residue at 3' position 9 is
      strongly preferred for transcription activity in the context of the genomic
      promoter, it does not signal transcription in the context of the antigenomic
      promoter. Therefore, our results show that the identity of 3' position 9 is
      crucial for signaling BUNV transcription; however, it is not the sole
      determinant.

PMID- 15731254
TI  - The influenza A virus M2 cytoplasmic tail is required for infectious virus
      production and efficient genome packaging.
AB  - The M2 integral membrane protein encoded by influenza A virus possesses an ion
      channel activity that is required for efficient virus entry into host cells. The
      role of the M2 protein cytoplasmic tail in virus replication was examined by
      generating influenza A viruses encoding M2 proteins with truncated C termini.
      Deletion of 28 amino acids (M2Stop70) resulted in a virus that produced fourfold
      fewer particles but >1,000-fold-fewer infectious particles than wild-type virus.
      Expression of the full-length M2 protein in trans restored the replication of the
      M2 truncated virus. Although the M2Stop70 virus particles were similar to wild
      type virus in morphology, the M2Stop70 virions contained reduced amounts of viral
      nucleoprotein and genomic RNA, indicating a defect in vRNP packaging. The data
      presented indicate the M2 cytoplasmic tail plays a role in infectious virus
      production by coordinating the efficient packaging of genome segments into
      influenza virus particles.

PMID- 15731255
TI  - Large-scale molecular characterization of adeno-associated virus vector
      integration in mouse liver.
AB  - Recombinant adeno-associated virus (rAAV) vector holds promise for gene therapy.
      Despite a low frequency of chromosomal integration of vector genomes, recent
      studies have raised concerns about the risk of rAAV integration because
      integration occurs preferentially in genes and accompanies chromosomal deletions,
      which may lead to loss-of-function insertional mutagenesis. Here, by analyzing
      347 rAAV integrations in mice, we elucidate novel features of rAAV integration:
      the presence of hot spots for integration and a strong preference for integrating
      near gene regulatory sequences. The most prominent hot spot was a harmless
      chromosomal niche in the rRNA gene repeats, whereas nearly half of the
      integrations landed near transcription start sites or CpG islands, suggesting the
      possibility of activating flanking cellular disease genes by vector integration,
      similar to retroviral gain-of-function insertional mutagenesis. Possible cancer
      related genes were hit by rAAV integration at a frequency of 3.5%. In addition,
      the information about chromosomal changes at 218 integration sites and 602
      breakpoints of vector genomes have provided a clue to how vector terminal repeats
      and host chromosomal DNA are joined in the integration process. Thus, the present
      study provides new insights into the risk of rAAV-mediated insertional
      mutagenesis and the mechanisms of rAAV integration.

PMID- 15731256
TI  - Analysis of human cytomegalovirus oriLyt sequence requirements in the context of
      the viral genome.
AB  - During the lytic phase of infection, replication of herpesvirus genomes initiates
      at the lytic origin of replication, oriLyt. Many herpesviruses harbor more than
      one lytic origin, but so far, only one oriLyt has been identified for human
      cytomegalovirus (HCMV). Evidence for the existence of additional lytic origins of
      HCMV has remained elusive. On the basis of transient replication assays with
      cloned viral fragments, HCMV oriLyt was described as a core region of 1.5 kbp
      (minimal oriLyt) flanked by auxiliary sequences required for maximal replication
      activity (complete oriLyt). It remained unclear whether minimal oriLyt alone can
      drive the replication of HCMV in the absence of its accessory regions. To
      investigate the sequence requirements of oriLyt in the context of the viral
      genome, mutant genomes were constructed lacking either minimal or complete
      oriLyt. These genomes were not infectious, suggesting that HCMV contains only one
      lytic origin of replication. Either minimal or complete oriLyt was then
      ectopically reinserted into the oriLyt-depleted genomes. Only the mutant genomes
      carrying complete oriLyt led to infectious progeny. Remarkably, inversion of the
      1.5-kbp core origin relative to its flanking regions resulted in a replication
      defective genome. Mutant genomes carrying minimal oriLyt plus the left flanking
      region gave rise to minifoci, but genomes harboring minimal oriLyt together with
      the right flanking region were noninfectious. We conclude that the previously
      defined minimal lytic origin is not sufficient to drive replication of the HCMV
      genome. Rather, our results underline the importance of the accessory regions and
      their correct arrangement for the function of HCMV oriLyt.

PMID- 15731257
TI  - Functional domains within the human immunodeficiency virus type 2 envelope
      protein required to enhance virus production.
AB  - Primate lentiviruses code for a protein that stimulates virus production. In
      human immunodeficiency virus type 1 (HIV-1), the activity is provided by the
      accessory protein, Vpu, while in HIV-2 and simian immunodeficiency virus it is a
      property of the envelope (Env) glycoprotein. Using a group of diverse
      retroviruses and cell types, we have confirmed the functional equivalence of the
      two proteins. However, despite these similarities, the two proteins have markedly
      different functional domains. While the Vpu activity is associated primarily with
      its membrane-spanning region, we have determined that the HIV-2 Env activity
      requires both the cytoplasmic tail and ectodomain of the protein, with the
      membrane-spanning domain being less important. Within the Env cytoplasmic tail,
      we further defined the necessary sequence as a membrane-proximal tyrosine-based
      motif. Providing the two Env regions separately as distinct CD8 chimeric proteins
      did not increase virus release. This suggests that the two domains must be either
      contained within a single protein or closely associated within a multiprotein
      oligomer, such as the Env trimer, in order to function. Finally, we observed that
      wild-type levels of incorporation of the HIV-2 Env into budding viruses were not
      required for this activity.

PMID- 15731258
TI  - Ligand-directed gene targeting to mammalian cells by pseudotype baculoviruses.
AB  - The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) can
      infect a variety of mammalian cells, as well as insect cells, facilitating its
      use as a viral vector for gene delivery into mammalian cells. Glycoprotein gp64,
      a major component of the budded AcMNPV envelope, is involved in viral entry into
      cells by receptor-mediated endocytosis and subsequent membrane fusion. We
      examined the potential production of pseudotype baculovirus particles transiently
      carrying ligands of interest in place of gp64 as a method of ligand-directed gene
      delivery into target cells. During amplification of a gp64-null pseudotype
      baculovirus carrying a green fluorescent protein gene in gp64-expressing insect
      cells, however, we observed the high-frequency appearance of a replication
      competent virus incorporating the gp64 gene into the viral genome. To avoid
      generation of replication-competent revertants, we prepared pseudotype
      baculoviruses by transfection with recombinant bacmids without further
      amplification in the gp64-expressing cells. We constructed gp64-null recombinant
      bacmids carrying cDNAs encoding either vesicular stomatitis virus G protein
      (VSVG) or measles virus receptors (CD46 or SLAM). The VSVG pseudotype baculovirus
      efficiently transduced a reporter gene into a variety of mammalian cell lines,
      while CD46 and SLAM pseudotype baculoviruses allowed ligand-receptor-directed
      reporter gene transduction into target cells expressing measles virus envelope
      glycoproteins. Gene transduction mediated by the pseudotype baculoviruses could
      be inhibited by pretreatment with specific antibodies. These results indicate the
      possible application of pseudotype baculoviruses in ligand-directed gene delivery
      into target cells.

PMID- 15731259
TI  - Immunologic pressure within class I-restricted cognate human immunodeficiency
      virus epitopes during highly active antiretroviral therapy.
AB  - Cytotoxic T lymphocytes (CTL) and highly active antiretroviral therapy (HAART)
      are known to exert strong evolutionary pressures on the virus population during
      human immunodeficiency virus (HIV) infection. However, it is not known whether
      CTL responses continue to substantially affect viral evolution during treatment.
      To study the effect of immunologic pressure on viral sequences during HAART, we
      identified 10 targeted HIV-specific CD8+-T-cell epitopes in five treatment-naive
      patients, sequenced each epitope in plasma-derived viruses, and then identified
      evidence of immunologic pressure at these epitopes by comparing the frequency of
      viral variants in plasma to the frequency of the CD8+-T-cell response for each
      variant identified. For one of the five patients, evidence of viral evolution was
      found during therapy. The sequence of the CTL-targeted epitope changed from an
      apparent escape variant prior to the initiation of therapy, to the sequence that
      is best recognized by the CTL response after the initiation of therapy, and then
      finally to a new escape variant during continued therapy. These data show that
      CTL-mediated pressure can continue to affect viral evolution after the initiation
      of HAART, even when treatment drives the viral load below detectable levels, and
      suggest that antiretroviral therapy may preferentially inhibit those virus
      variants that escape the CTL response.

PMID- 15731260
TI  - Analysis of nucleotide sequences and multimeric forms of a novel satellite RNA
      associated with beet black scorch virus.
AB  - The full-length sequence of a satellite RNA (sat-RNA) of Beet black scorch virus
      isolate X (BBSV-X) was determined. This agent is 615 nucleotides long and lacks
      extensive sequence homology with its helper virus or with other reported viruses.
      Purified virus particles contained abundant single-stranded plus-sense monomers
      and smaller amounts of dimers. Single-stranded RNAs from total plant RNA extracts
      also included primarily monomers and smaller amounts of dimers that could be
      revealed by hybridization, and preparations of purified double-stranded RNAs also
      contained monomers and dimers. Coinoculation of in vitro transcripts of sat-RNA
      to Chenopodium amaranticolor with BBSV RNAs was used to assess the replication
      and accumulation of various forms of sat-RNA, including monomers, dimers, and
      tetramers. Dimeric sat-RNAs with 5- or 10-base deletions or 15-base insertions
      within the junction regions accumulated preferentially. In contrast, the
      replication of monomeric sat-RNA was severely inhibited by five-nucleotide
      deletions in either the 5' or the 3' termini. Therefore, sequences at both the 5'
      and the 3' ends of the monomers or the presence of intact juxtaposed multimers is
      essential for the replication of sat-RNA and for the predomination of monomeric
      progeny. Comparisons of the time courses of replication initiated by in vitro
      synthesized monomeric or multimeric sat-RNAs raised the possibility that the
      dimeric form has an intermediate role in replication. We propose that replication
      primarily involves multimers, possibly as dimeric forms. These forms may revert
      to monomers by a termination of replication at 5' end sequences and/or by
      internal initiation at the 3' ends of multimeric junctions.

PMID- 15731261
TI  - Long-term cytomegalovirus infection leads to significant changes in the
      composition of the CD8+ T-cell repertoire, which may be the basis for an
      imbalance in the cytokine production profile in elderly persons.
AB  - In spite of the present belief that latent cytomegalovirus (CMV) infection drives
      CD8+ T-cell differentiation and induces premature immune senescence, no
      systematic studies have so far been performed to compare phenotypical and
      functional changes in the CD8+ T-cell repertoire in CMV-infected and noninfected
      persons of different age groups. In the present study, number, cytokine
      production, and growth potential of naive (CD45RA+ CD28+), memory (CD45RA-
      CD28+), and effector (CD45RA+ CD28- or CD45RA- CD28-) CD8+ T cells were analyzed
      in young, middle-aged, and elderly clinically healthy persons with a positive or
      negative CMV antibody serology. Numbers and functional properties of CMVpp65(495
      503)-specific CD8+ T cells were also studied. We demonstrate that aging as well
      as CMV infection lead to a decrease in the size of the naive CD8+ T-cell pool but
      to an increase in the number of CD8+ effector T cells, which produce gamma
      interferon but lack substantial growth potential. The size of the CD8+ memory T
      cell population, which grows well and produces interleukin-2 (IL-2) and IL-4,
      also increases with aging, but this increase is missing in CMV carriers. Life
      long latent CMV infection seems thus to diminish the size of the naive and the
      early memory T-cell pool and to drive a Th1 polarization within the immune
      system. This can lead to a reduced diversity of CD8 responses and to chronic
      inflammatory processes which may be the basis of severe health problems in
      elderly persons.

PMID- 15731262
TI  - Amsacta moorei Entomopoxvirus inhibitor of apoptosis suppresses cell death by
      binding Grim and Hid.
AB  - Inhibitor of apoptosis (iap) genes have been identified in the genomes of two
      independent families of insect viruses, the Baculoviridae and the
      Entomopoxvirinae. In this report, we examined the functional attributes of the
      Amsacta moorei entomopoxvirus-encoded IAP protein (AMV-IAP). The binding
      specificity of the individual baculoviral IAP repeat (BIR) domains of AMV-IAP was
      investigated by using a random-peptide, phage display library, and sequences
      similar to the amino termini of proapoptotic Drosophila proteins in the
      Reaper/Hid/Grim family were identified. Furthermore, the BIR domains of AMV-IAP
      protein were demonstrated to bind the mammalian IAP inhibitor Smac through the
      AVPI tetrapeptide sequence, suggesting that the peptide binding pocket and groove
      found in the insect and mammalian IAPs is conserved in this viral protein.
      Interaction analysis implicated BIR1 as the high-affinity site for Grim, while
      BIR2 interacted more strongly with Hid. Both Grim and Hid were demonstrated to
      interact with AMV-IAP in vivo, and Grim- or Hid-induced cell death was suppressed
      when AMV-IAP was coexpressed.

PMID- 15731263
TI  - Characterization of highly pathogenic H5N1 avian influenza A viruses isolated
      from South Korea.
AB  - An unprecedented outbreak of H5N1 highly pathogenic avian influenza (HPAI) has
      been reported for poultry in eight different Asian countries, including South
      Korea, since December 2003. A phylogenetic analysis of the eight viral genes
      showed that the H5N1 poultry isolates from South Korea were of avian origin and
      contained the hemagglutinin and neuraminidase genes of the A/goose/Guangdong/1/96
      (Gs/Gd) lineage. The current H5N1 strains in Asia, including the Korean isolates,
      share a gene constellation similar to that of the Penfold Park, Hong Kong,
      isolates from late 2002 and contain some molecular markers that seem to have been
      fixed in the Gs/Gd lineage virus since 2001. However, despite genetic
      similarities among recent H5N1 isolates, the topology of the phylogenetic tree
      clearly differentiates the Korean isolates from the Vietnamese and Thai isolates
      which have been reported to infect humans. A representative Korean isolate was
      inoculated into mice, with no mortality and no virus being isolated from the
      brain, although high titers of virus were observed in the lungs. The same
      isolate, however, caused systemic infections in chickens and quail and killed all
      of the birds within 2 and 4 days of intranasal inoculation, respectively. This
      isolate also replicated in multiple organs and tissues of ducks and caused some
      mortality. However, lower virus titers were observed in all corresponding tissues
      of ducks than in chicken and quail tissues, and the histological lesions were
      restricted to the respiratory tract. This study characterizes the molecular and
      biological properties of the H5N1 HPAI viruses from South Korea and emphasizes
      the need for comparative analyses of the H5N1 isolates from different countries
      to help elucidate the risk of a human pandemic from the strains of H5N1 HPAI
      currently circulating in Asia.

PMID- 15731264
TI  - BFRF1 of Epstein-Barr virus is essential for efficient primary viral envelopment
      and egress.
AB  - The molecular mechanisms that underlie maturation and egress of Epstein-Barr
      virus (EBV) virions are only partially characterized. We have recently shown that
      the BFRF1 gene, the EBV positional homolog of herpes simplex virus type 1 and
      pseudorabies virus UL34, is expressed early during EBV lytic replication and that
      it is found predominantly on the nuclear membrane (A. Farina, R. Santarelli, R.
      Gonnella, R. Bei, R. Muraro, G. Cardinali, S. Uccini, G. Ragona, L. Frati, A.
      Faggioni, and A. Angeloni, J. Virol. 74:3235-3244, 2000). These data suggest that
      the BFRF1 protein might be involved in viral primary envelopment. To precisely
      determine the function of this protein, we have constructed an EBV mutant devoid
      of the BFRF1 gene (BFRF1-KO). 293 cells carrying BFRF1-KO showed no differences
      in comparison with wild-type EBV in terms of DNA lytic replication or expression
      of late viral proteins upon induction of the lytic cycle. However, binding assays
      and infection experiments using cell lines or human cord blood lymphocytes showed
      a clear reduction in the viral mutant titers. Complementation experiments with
      BFRF1-KO and a BFRF1 expression vector restored viral titers to levels similar to
      those for the wild-type control, showing that the modifications that we
      introduced were limited to the BFRF1 gene. Electron microscopic observations
      showed that the reduction in viral titers was due to sequestration of EBV
      nucleocapsids in the nuclei of lytically induced cells. This suggests that BFRF1
      is involved in transport of the maturing virion across the nuclear membrane. This
      hypothesis was further supported by the observation that BFRF1 is present in
      maturing intracellular virions but not in their extracellular counterparts. This
      implies that BFRF1 is a key protein for EBV maturation.

PMID- 15731265
TI  - Characterization and intracellular localization of the Epstein-Barr virus protein
      BFLF2: interactions with BFRF1 and with the nuclear lamina.
AB  - We have reported in the accompanying paper that the BFRF1 protein of Epstein-Barr
      virus (EBV) is important for efficient primary viral envelopment and egress (A.
      Farina, R. Feederle, S. Raffa, R. Gonnella, R. Santarelli, L. Frati, A. Angeloni,
      M. R. Torrisi, A. Faggioni, and H.-J. Delecluse, J. Virol. 79:3703-3712). Here we
      describe the characterization of the product of the EBV BFLF2 gene, which belongs
      to a family of conserved herpesviral genes which include the UL31 genes of herpes
      simplex virus and of pseudorabies virus and whose products are known to interact
      with UL34, the positional homolog of BFRF1. BFLF2 is an early transcript and is
      expressed in a variety of cell lines upon EBV lytic cycle activation. Western
      blotting of purified virion preparations showed that BFLF2 is a component of
      intracellular virions but is absent from mature extracellular virions.
      Coimmunoprecipitation experiments indicated that BFLF2 interacts with BFRF1,
      which was confirmed by immunofluorescence confocal microscopy showing that the
      two proteins colocalize on the nuclear membrane not only upon cotransfection in
      epithelial cells but also during viral replication. In cells carrying an EBV
      mutant with the BFRF1 gene deleted (293-BFRF1-KO cells) BFLF2 expression was low,
      and it was restored to wild-type levels upon treatment of the cells with the
      proteasome inhibitor MG132. Furthermore, recomplementing the 293-BFRF1-KO cells
      by BFRF1 transfection restored BFLF2 expression to the wild-type level. In
      addition, when expressed alone BFLF2 was localized diffusely inside the nucleus,
      whereas in the presence of BFRF1 the two proteins colocalized at the nuclear rim.
      Finally, 293 epithelial cells transfected with either protein or cotransfected
      were analyzed by electron microscopy to investigate potential alterations in the
      morphology of the nuclear membrane. The ultrastructural analysis revealed that
      (i) BFRF1 caused duplications of the nuclear membrane, similar to those reported
      to occur during the course of herpesviral replication, and (ii) while BFLF2 alone
      did not cause any apparent alteration, coexpression of the two proteins
      dramatically induced profound convolutions of the duplicated nuclear membrane.
      Both biochemical and morphological analysis showed association of the BFRF1-BFLF2
      complex with a component of the nuclear lamina, lamin B. Taken together, these
      results and those of the accompanying paper (Farina et al., J. Virol. 79:3703
      3712) indicate an important role of BFRF1 and BFLF2 in the early steps of EBV
      maturation at the nuclear membrane.

PMID- 15731266
TI  - Inhibition of viral replication by ribozyme: mutational analysis of the site and
      mechanism of antiviral activity.
AB  - A controlled mutational study was used to determine the site and mechanism of the
      antiviral action of ribozymes that inhibit Sindbis virus replication. A hairpin
      ribozyme targeting G575 of the Sindbis virus genomic RNA was designed and cloned
      into a minimized alphavirus amplicon vector. Cells that were stably transfected
      with this construct expressed low levels of a constitutive transcript containing
      the ribozyme plus recognition sequences for Sindbis RNA replicase. Upon
      infection, the ribozyme transcript was amplified to high levels by the viral
      replicase, resulting in decreased viral production from infected ribozyme
      expressing cells. Mutations were then introduced into the viral RNA target
      sequence to interfere with ribozyme binding, and compensatory changes were
      generated in the ribozyme recognition sequence. Single mutations in the virus or
      ribozyme decreased the efficacy of the ribozyme's inhibition of viral
      replication, and compensatory mutations restored it. To confirm that ribozyme
      catalyzed RNA cleavage was actually needed for inhibition, we performed tests
      with a cell line expressing an inactivated ribozyme and with a virus containing a
      single nucleotide target mutation that allowed the ribozyme to bind but blocked
      cleavage at the recognition site. The results show that most of the antiviral
      activity of ribozymes is due to ribozyme-catalyzed cleavage at the targeted RNA
      sequence, but some additional inhibition seems to occur through an antisense
      mechanism.

PMID- 15731267
TI  - The global transcriptional effects of the human papillomavirus E6 protein in
      cervical carcinoma cell lines are mediated by the E6AP ubiquitin ligase.
AB  - The function of the human papillomavirus (HPV) E6 protein that is most clearly
      linked to carcinogenesis is the targeted degradation of p53, which is dependent
      on the E6AP ubiquitin ligase. Additional functions have been attributed to E6,
      including the stimulation of telomerase activity and the targeted degradation of
      other cellular proteins, but in most cases it is unclear whether these activities
      are also E6AP dependent. While E6 clearly influences the transcriptional program
      of HPV-positive cell lines through the inactivation of p53, it has been shown
      that at least a subset of its p53-independent functions are also reflected in the
      transcriptional program. For this study, we have determined the extent to which
      E6AP is involved in mediating the set of E6 functions that impact on the global
      transcriptional program of HPV-positive cell lines. The transcriptional profiles
      of approximately 31,000 genes were characterized for three cell lines (HeLa,
      Caski, and SiHa cells) after small interfering RNA (siRNA)-mediated silencing of
      E6 or E6AP. We found that E6 and E6AP siRNAs elicited nearly identical
      alterations in the transcriptional profile of each cell line. Some of the
      expression alterations were apparent secondary effects of p53 stabilization,
      while the basis of most other changes was not reconcilable with previously
      proposed E6 functions. While expression changes of the TERT gene (telomerase
      catalytic subunit) were not revealed by the array, telomerase repeat
      amplification protocol assays showed that both E6 and E6AP knockouts resulted in
      a suppression of telomerase activity. Together, these results suggest that E6AP
      mediates a broad spectrum of E6 functions, including virtually all functions that
      impact on the transcriptional program of HPV-positive cell lines.

PMID- 15731268
TI  - Enhanced cellular immunity in macaques following a novel peptide immunotherapy.
AB  - Advances in treating and preventing AIDS depend on understanding how human
      immunodeficiency virus (HIV) is eliminated in vivo and on the manipulation of
      effective immune responses to HIV. During the development of assays quantifying
      the elimination of fluorescent autologous cells coated with overlapping 15-mer
      simian immunodeficiency virus (SIV) or HIV-1 peptides, we made a remarkable
      observation: the reinfusion of macaque peripheral blood mononuclear cells, or
      even whole blood, pulsed with SIV and/or HIV peptides generated sharply enhanced
      SIV- and HIV-1-specific T-cell immunity. Strong, broad CD4+- and CD8+-T-cell
      responses could be enhanced simultaneously against peptide pools spanning 87% of
      all SIV- and HIV-1-expressed proteins-highly desirable characteristics of HIV
      specific immunity. De novo hepatitis C virus-specific CD4+- and CD8+-T-cell
      responses were generated in macaques by the same method. This simple technique
      holds promise for the immunotherapy of HIV and other chronic viral infections.

PMID- 15731269
TI  - Structural analysis of tobacco etch potyvirus HC-pro oligomers involved in aphid
      transmission.
AB  - Oligomeric forms of the HC-Pro protein of the tobacco etch potyvirus (TEV) have
      been analyzed by analytical ultracentrifugation and single-particle electron
      microscopy combined with three-dimensional (3D) reconstruction. Highly purified
      HC-Pro protein was obtained from plants infected with TEV by using a modified
      version of the virus that incorporates a histidine tag at the HC-Pro N terminus
      (hisHC-Pro). The purified protein retained a high biological activity in solution
      when tested for aphid transmission. Sedimentation equilibrium showed that the
      hisHC-Pro preparations were heterogeneous in size. Sedimentation velocity
      confirmed the previous observation and revealed that the active protein solution
      contained several sedimenting species compatible with dimers, tetramers,
      hexamers, and octamers of the protein. Electron microscopy fields of purified
      protein showed particles of different sizes and shapes. The reconstructed 3D
      structures suggested that the observed particles could correspond to dimeric,
      tetrameric, and hexameric forms of the protein. A model of the interactions
      required for oligomerization of the HC-Pro of potyviruses is proposed.

PMID- 15731270
TI  - Importance of both the coding and the segment-specific noncoding regions of the
      influenza A virus NS segment for its efficient incorporation into virions.
AB  - The genome of influenza A virus consists of eight single-strand negative-sense
      RNA segments, each comprised of a coding region and a noncoding region. The
      noncoding region of the NS segment is thought to provide the signal for
      packaging; however, we recently showed that the coding regions located at both
      ends of the hemagglutinin and neuraminidase segments were important for their
      incorporation into virions. In an effort to improve our understanding of the
      mechanism of influenza virus genome packaging, we sought to identify the regions
      of NS viral RNA (vRNA) that are required for its efficient incorporation into
      virions. Deletion analysis showed that the first 30 nucleotides of the 3' coding
      region are critical for efficient NS vRNA incorporation and that deletion of the
      3' segment-specific noncoding region drastically reduces NS vRNA incorporation
      into virions. Furthermore, silent mutations in the first 30 nucleotides of the 3'
      NS coding region reduced the incorporation efficiency of the NS segment and
      affected virus replication. These results suggested that segment-specific
      noncoding regions together with adjacent coding regions (especially at the 3'
      end) form a structure that is required for efficient influenza A virus vRNA
      packaging.

PMID- 15731271
TI  - The C-terminal half of TSG101 blocks Rous sarcoma virus budding and sequesters
      Gag into unique nonendosomal structures.
AB  - Retroviral late domains (L domains) are short amino acid sequences in the Gag
      protein that facilitate the process of budding. L domains act by recruiting the
      ESCRT complexes, which normally function in the formation of multivesicular
      bodies. The PTAP late domain of human immunodeficiency virus (HIV) is believed to
      specifically recruit this machinery by binding the ESCRT protein TSG101. It was
      recently demonstrated that expression of a C-terminal fragment of TSG101 (TSG-3')
      blocked the budding of both PTAP-dependent and PPPY-dependent retroviruses. We
      show here that TSG-3' expression leads to the formation of large spherical
      entities that we call TICS (TSG-3'-induced cellular structures) in the cytoplasm.
      Rous sarcoma virus (RSV) and murine leukemia virus (MLV) Gag proteins are
      selectively recruited to these structures, but HIV type 1 Gag is completely
      excluded. Experiments with various HIV and RSV vector constructs as well as HIV
      and RSV chimeras suggest that recruitment to the TICS is late domain independent
      and does not involve recognition of any single amino acid sequence. TICS appear
      to have no limiting membrane and do not colocalize with markers for any
      membranous cellular compartment. Wild-type TSG101 is also recruited to TICS, but
      most other ESCRT proteins are excluded. These structures are similar in nature to
      aggresomes, colocalize with the aggresome marker GFP-250, and are highly enriched
      in ubiquitin but in other ways do not fully meet the description of aggresomes.
      We conclude that the block to retroviral budding by TSG-3' may be the result of
      its sequestration of Gag, depletion of free TSG101, or depletion of free
      ubiquitin.

PMID- 15731272
TI  - The E2 glycoprotein of classical swine fever virus is a virulence determinant in
      swine.
AB  - To identify genetic determinants of classical swine fever virus (CSFV) virulence
      and host range, chimeras of the highly pathogenic Brescia strain and the
      attenuated vaccine strain CS were constructed and evaluated for viral virulence
      in swine. Upon initial screening, only chimeras 138.8v and 337.14v, the only
      chimeras containing the E2 glycoprotein of CS, were attenuated in swine despite
      exhibiting unaltered growth characteristics in primary porcine macrophage cell
      cultures. Additional viral chimeras were constructed to confirm the role of E2 in
      virulence. Chimeric virus 319.1v, which contained only the CS E2 glycoprotein in
      the Brescia background, was markedly attenuated in pigs, exhibiting significantly
      decreased virus replication in tonsils, a transient viremia, limited
      generalization of infection, and decreased virus shedding. Chimeras encoding all
      Brescia structural proteins in a CS genetic background remained attenuated,
      indicating that additional mutations outside the structural region are important
      for CS vaccine virus attenuation. These results demonstrate that CS E2 alone is
      sufficient for attenuating Brescia, indicating a significant role for the CSFV E2
      glycoprotein in swine virulence.

PMID- 15731273
TI  - Identification of an essential domain in the herpes simplex virus 1 UL34 protein
      that is necessary and sufficient to interact with UL31 protein.
AB  - Previous results have indicated that the herpes simplex virus 1 UL31 and UL34
      proteins interact and form a complex at the inner nuclear membranes of infected
      cells, where both play important roles in the envelopment of nucleocapsids at the
      inner nuclear membrane. In the work described here, mapping studies using
      glutathione S-transferase pull-down assays indicated that amino acids 137 to 181
      of the UL34 protein are sufficient to mediate an interaction with the UL31
      protein. A recombinant virus (v3480) lacking UL34 codons 138 to 181 was
      constructed. Similar to a UL34 null virus, v3480 failed to replicate on Vero
      cells and grew to a limited extent on rabbit skin cells. A UL34-expressing cell
      line restored v3480 growth and plaque formation. Similar to the localization of
      UL31 protein in cells infected with a UL34 null virus, the UL31 protein was
      present in the nuclei of Hep2 cells infected with v3480. Hep2 cells infected with
      v3480 contained the UL34 protein in the cytoplasm, the nucleus, and the nuclear
      membrane, and this was noted to be similar to the appearance of cells infected
      with a UL31 null virus. In transient expression assays, the interaction between
      UL34 amino acids 137 to 181 and the UL31 protein was sufficiently robust to
      target green fluorescent protein and emerin to intranuclear sites that contained
      the UL31 protein. These data indicate that amino acids 137 to 181 of the UL34
      protein are (i) sufficient to mediate interactions with the UL31 protein in vitro
      and in vivo, (ii) necessary for the colocalization of UL31 and UL34 in infected
      cells, and (iii) essential for normal viral replication.

PMID- 15731276
TI  - Functional analysis of the pseudorabies virus UL51 protein.
AB  - Homologs of the UL51 protein of herpes simplex virus have been identified in all
      herpesvirus subfamilies, but until now, no function has been assigned to any of
      them. To investigate function of the UL51 gene product of the alphaherpesvirus
      pseudorabies virus (PrV), we isolated and analyzed a mutant lacking the major
      part of the open reading frame, PrV-DeltaUL51F, and a rescuant. One-step growth
      analysis of PrV-DeltaUL51F revealed only slightly reduced titers, but plaque size
      was notably diminished and reached only approximately 30% the plaque size of wild
      type PrV. Ultrastructurally, intracytoplasmic capsids were found in large numbers
      either without envelope or in different stages of envelopment, indicating that
      secondary envelopment in the cytoplasm was less efficient. However, neuroinvasion
      in the mouse trigeminal pathway after intranasal infection was only slightly
      delayed. A PrV UL11 mutant also showed a defect in secondary envelopment (M.
      Kopp, H. Granzow, W. Fuchs, B. G. Klupp, E. Mundt, A. Karger, and T. C.
      Mettenleiter, J. Virol. 77:5339-5351, 2003). Since both proteins are part of the
      viral tegument and are predicted to be membrane associated, they may serve
      similar, possibly redundant functions during viral morphogenesis. Therefore, we
      also isolated a mutant simultaneously lacking UL51 and UL11. This mutant
      exhibited further reduced plaque size compared to the single-deletion mutants,
      but viral titers were comparable to those for the UL11 mutant. In electron
      microscopic analyses, the observed defect in secondary envelopment was similar to
      that found in the UL11 single-deletion mutant. In conclusion, both conserved
      tegument proteins, either singly or in combination, are involved in virion
      morphogenesis in the cytoplasm but are not essential for viral replication in
      vitro and in vivo.

PMID- 15731275
TI  - Complementarity in the supramolecular design of arenaviruses and retroviruses
      revealed by electron cryomicroscopy and image analysis.
AB  - Arenaviruses are rodent-borne agents of diseases, including potentially lethal
      human hemorrhagic fevers. These enveloped viruses encapsidate a bisegmented
      ambisense single-stranded RNA genome that can be packaged in variable copy
      number. Electron cryomicroscopy and image analysis of New World Pichinde and
      Tacaribe arenaviruses and Old World lymphocytic choriomeningitis virus revealed
      pleomorphic enveloped particles ranging in diameter from approximately 400 to
      approximately 2,000 A. The surface spikes were spaced approximately 100 A apart
      and extended approximately 90 A from the maximum phospholipid headgroup density
      of the outer bilayer leaflet. Distinctive stalk and head regions extended
      radially approximately 30 and approximately 60 A from the outer bilayer leaflet,
      respectively. Two interior layers of density apposed to the inner leaflet of the
      viral lipid bilayer were assigned as protein Z and nucleoprotein (NP) molecules
      on the basis of their appearance, spacing, and projected volume. Analysis of en
      face views of virions lacking the GP-C spikes showed reflections consistent with
      paracrystalline packing of the NP molecules in a lattice with edges of
      approximately 57 and approximately 74 A. The structural proteins of retroviruses
      and arenaviruses assemble with similar radial density distributions, using common
      cellular components.

PMID- 15731274
TI  - Size heterogeneity in the 3' noncoding region of South American isolates of
      yellow fever virus.
AB  - The 3' noncoding region (3' NCR) of flaviviruses contains secondary and tertiary
      structures essential for virus replication. Previous studies of yellow fever
      virus (YFV) and dengue virus have found that modifications to the 3' NCR are
      sometimes associated with attenuation in vertebrate and/or mosquito hosts. The 3'
      NCRs of 117 isolates of South American YFV have been examined, and major
      deletions and/or duplications of conserved RNA structures have been identified in
      several wild-type isolates. Nineteen isolates (designated YF-XL isolates) from
      Brazil, Trinidad, and Venezuela, dating from 1973 to 2001, exhibited a 216
      nucleotide (nt) duplication, yielding a tandem repeat of conserved hairpin, stem
      loop, dumbbell, and pseudoknot structures. YF-XL isolates were found exclusively
      within one subclade of South American genotype I YFV. One Brazilian isolate
      exhibited, in addition to the 216-nt duplication, a deletion of a 40-nt repeated
      hairpin (RYF) motif (YF-XL-DeltaRYF). To investigate the biological significance
      of these 3' NCR rearrangements, YF-XL-DeltaRYF and YF-XL isolates, as well as
      other South American YFV isolates, were evaluated for three phenotypes: growth
      kinetics in cell culture, neuroinvasiveness in suckling mice, and ability to
      replicate and produce disseminated infections in Aedes aegypti mosquitoes. YF-XL
      DeltaRYF and YF-XL isolates showed growth kinetics and neuroinvasive
      characteristics comparable to those of typical South American YFV isolates, and
      mosquito infectivity trials demonstrated that both types of 3' NCR variants were
      capable of replication and dissemination in a laboratory-adapted colony of A.
      aegypti.

PMID- 15731277
TI  - Deletion of the second immunoglobulin-like domain of nectin-1 alters its
      intracellular processing and localization and ability to mediate entry of herpes
      simplex virus.
AB  - Nectin-1 is an immunoglobulin (Ig)-like entry receptor for herpes simplex virus
      (HSV). Like other nectins, nectin-1 forms dimers and mediates cell adhesion
      through interactions with other nectins. We constructed a second-domain deletion
      mutant of nectin-1 (nectin-1-Delta2) to examine the role of the second Ig-like
      domain in HSV entry. Nectin-1-Delta2 exhibited a severely reduced ability to
      mediate HSV entry and accumulated in the endoplasmic reticulum but retained the
      ability to interact with its HSV ligand, gD. The failure of nectin-1-Delta2 to
      mediate HSV entry probably resulted from its failure to be transported to a
      membrane targeted by HSV for viral entry.

PMID- 15731278
TI  - Exogenous ACE2 expression allows refractory cell lines to support severe acute
      respiratory syndrome coronavirus replication.
AB  - Of 30 cell lines and primary cells examined, productive severe acute respiratory
      syndrome coronavirus (Urbani strain) (SARS-CoV) infection after low-multiplicity
      inoculation was detected in only six: three African green monkey kidney
      epithelial cell lines (Vero, Vero E6, and MA104), a human colon epithelial line
      (CaCo-2), a porcine kidney epithelial line [PK(15)], and mink lung epithelial
      cells (Mv 1 Lu). SARS-CoV produced a lytic infection in Vero, Vero E6, and MA104
      cells, but there was no visible cytopathic effect in Caco-2, Mv 1 Lu, or PK(15)
      cells. Multistep growth kinetics were identical in Vero E6 and MA104 cells, with
      maximum titer reached 24 h postinoculation (hpi). Virus titer was maximal 96 hpi
      in CaCo-2 cells, and virus was continually produced from infected CaCo-2 cells
      for at least 6 weeks after infection. CaCo-2 was the only human cell type of 13
      tested that supported efficient SARS-CoV replication. Expression of the SARS-CoV
      receptor, angiotensin-converting enzyme 2 (ACE2), resulted in SARS-CoV
      replication in all refractory cell lines examined. Titers achieved were variable
      and dependent upon the method of ACE2 expression.

PMID- 15731279
TI  - Lambda interferon inhibits hepatitis B and C virus replication.
AB  - Lambda interferon (IFN-lambda) induces an intracellular IFN-alpha/beta-like
      antiviral response through a receptor complex distinct from the IFN-alpha/beta
      receptor. We therefore determined the ability of IFN-lambda to inhibit hepatitis
      B virus (HBV) and hepatitis C virus (HCV) replication. IFN-lambda inhibits HBV
      replication in a differentiated murine hepatocyte cell line with kinetics and
      efficiency similar to IFN-alpha/beta and does not require the expression of IFN
      alpha/beta or IFN-gamma. Furthermore, IFN-lambda blocked the replication of a
      subgenomic and a full-length genomic HCV replicon in human hepatocyte Huh7 cells.
      These results suggest the possibility that IFN-lambda may be therapeutically
      useful in the treatment of chronic HBV or HCV infection.

PMID- 15731280
TI  - Improving the safety of a conditional-live human immunodeficiency virus type 1
      vaccine by controlling both gene expression and cell entry.
AB  - Live attenuated human immunodeficiency virus type 1 (HIV-1) vaccines are
      considered unsafe because faster-replicating pathogenic virus variants may evolve
      after vaccination. We previously presented a conditional-live HIV-1 variant of
      which replication can be switched off as an alternative vaccination strategy. To
      improve the safety of such a vaccine, we constructed a new HIV-1 variant that
      depends not only on doxycycline for gene expression but also on the T20 peptide
      for cell entry. Replication of this virus can be limited to the level required to
      induce the immune system by transient administration of doxycycline and T20.
      Subsequent withdrawal of these inducers efficiently blocks viral replication and
      evolution.

PMID- 15731281
TI  - Pairs of Vp1 cysteine residues essential for simian virus 40 infection.
AB  - Transient disulfide bonding occurs during the intracellular folding and
      pentamerization of simian virus 40 (SV40) major capsid protein Vp1 (P. P. Li, A.
      Nakanishi, S. W. Clark, and H. Kasamatsu, Proc. Natl. Acad. Sci. USA 99:1353
      1358, 2002). We investigated the requirement for Vp1 cysteine pairs during SV40
      infection. Our analysis identified three Vp1 double-cysteine mutant combinations
      that abolished viability as assayed by plaque formation. Mutating the Cys49-Cys87
      pair or the Cys87-Cys254 pair led to ineffective nuclear localization and
      diminished accumulation of the mutant Vp1s, and the defect extended in a dominant
      negative manner to the wild-type minor capsid proteins Vp2/3 and an affinity
      tagged recombinant Vp1 expressed in the same cells. Mutating the Cys87-Cys207
      pair preserved the nuclear localization and normal accumulation of the capsid
      proteins but diminished the production of virus-like particles. Our results are
      consistent with a role for Cys49, Cys87, and Cys254 in the folding and
      cytoplasmic-nuclear trafficking of Vp1 and with a role for Cys87 and Cys207 in
      the assembly of infectious particles. These findings suggest that transient
      disulfide bond formation between certain Vp1 cysteine residues functions at two
      stages of SV40 infection: during Vp1 folding and oligomerization in the cytoplasm
      and during virion assembly in the nucleus.

PMID- 15731282
TI  - Endocytosis of the Nipah virus glycoproteins.
AB  - Nipah virus (NiV), a highly pathogenic member of the family Paramyxoviridae,
      encodes the surface glycoproteins F and G. Since internalization of the NiV
      envelope proteins from the cell surface might be of functional importance for
      viral pathogenesis either by regulating cytopathogenicity or by modulating
      recognition of infected cells by the immune system, we analyzed the endocytosis
      of the NiV F and G proteins. Interestingly, we found both glycoproteins to be
      internalized in infected and transfected cells. As endocytosis is normally
      mediated by tyrosine- or dileucine-dependent signals in the cytoplasmic tails of
      transmembrane proteins, all potential internalization signals in the NiV
      glycoproteins were mutated. Whereas the G protein appeared to be constitutively
      internalized with the bulk flow during membrane turnover, uptake of the F protein
      was found to be signal mediated. F endocytosis clearly depended on a membrane
      proximal YXXPhi motif and was found to be of functional importance for the
      biological activity of the protein.

PMID- 15731283
TI  - Human cytomegalovirus immediate-early 2 gene expression blocks virus-induced beta
      interferon production.
AB  - The effect of human cytomegalovirus (HCMV) gene expression on beta interferon
      (IFN-beta) expression was examined. We demonstrate that the HCMV immediate-early
      2 (IE2) gene product IE86 can effectively block the induction of IFN-beta during
      HCMV infection. IE86 also efficiently blocked the induction of IFN-beta following
      Sendai virus infection, demonstrating that IE86's ability to block induction of
      IFN-beta is not limited to HCMV infection, identifying IE2 as an IFN-beta
      antagonist.

PMID- 15731284
TI  - Splicing of rhesus rhadinovirus R15 and ORF74 bicistronic transcripts during
      lytic infection and analysis of effects on production of vCD200 and vGPCR.
AB  - Rhesus macaque rhadinovirus (RRV) is the rhesus macaque homologue of human
      herpesvirus 8 (HHV-8). Here we examine expression of RRV R15 and ORF74,
      homologues of K14 and ORF74 of HHV-8, respectively. As in HHV-8, transcripts
      encoding RRV R15 and ORF74 are bicistronic. However, unlike what has been
      suggested for HHV-8, RRV R15- and ORF74-encoding transcripts are expressed late
      during lytic infection and undergo unique splicing events that result in the
      production of transcripts capable of encoding vGPCR, as well as membrane
      associated and secreted forms of vCD200. The alternative splicing for vCD200 has
      implications for viral pathogenesis.

PMID- 15731285
TI  - Novel polyomavirus detected in the feces of a chimpanzee by nested broad-spectrum
      PCR.
AB  - In order to screen for new polyomaviruses in samples derived from various animal
      species, degenerated PCR primer pairs were constructed. By using a nested PCR
      protocol, the sensitive detection of nine different polyomavirus genomes was
      demonstrated. The screening of field samples revealed the presence of a new
      polyomavirus, tentatively designated chimpanzee polyomavirus (ChPyV), in the
      feces of a juvenile chimpanzee (Pan troglodytes). Analysis of the region encoding
      the major capsid protein VP1 revealed a unique insertion in the EF loop of the
      protein and showed that ChPyV is a distinct virus related to the monkey
      polyomavirus B-lymphotropic polyomavirus and the human polyomavirus JC
      polyomavirus.

PMID- 15731286
TI  - A re-examination of the whiplash associated disorders (WAD) as a systemic
      illness.
AB  - OBJECTIVE: To describe the systemic nature of the illness reported after motor
      vehicle collisions using data from a large, population based cohort of
      individuals making an injury insurance claim. METHODS: All subjects who submitted
      a claim or were treated for whiplash injury following a motor vehicle collision
      in Saskatchewan, Canada during an 18 month period were examined. Demographics of
      claimants, collision related data, pre-collision health data, symptom prevalence,
      and scores on the short form 36 item general health survey (SF-36) were obtained
      on average within one month post-collision. RESULTS: Of 9006 potentially eligible
      claimants, 7462 (83%) met criteria for whiplash injury and provided information
      regarding demographics and injury related symptoms; 45% of these consented to
      complete the SF-36 at baseline. For most subjects, neck pain was only one of many
      diffuse and intense symptoms, including, often, low back pain. The range of
      symptoms, including fatigue, dizziness, paraesthesiae, headache, spinal pain,
      nausea, and jaw pain, could be interpreted as a systemic disorder. SF-36 scores
      showed low physical and mental functioning one month post-collision. CONCLUSIONS:
      What is commonly referred to as whiplash associated disorders (WAD) is best
      appreciated as a syndrome extending well beyond what can be labelled as a neck
      injury. More research is needed for a better understanding of the underlying
      mechanisms involved so that treatment can be directed at the broad spectrum of
      the illness rather than focusing on finding a focal neck injury.

PMID- 15731287
TI  - Investigation of polymorphisms in the PADI4 gene in determining severity of
      inflammatory polyarthritis.
AB  - BACKGROUND: A functional haplotype of the peptidylarginine deiminase 4 (PADI4)
      gene has recently been identified as a rheumatoid arthritis susceptibility gene
      in a Japanese but not in a UK population. One possible explanation for this
      disparity is that the gene determines severity of rather than susceptibility to
      inflammatory polyarthritis (IP) and that the UK and Japanese cohorts differed in
      terms of outcome. AIM: To examine the association between individual PADI4 single
      nucleotide polymorphisms (SNPs) and haplotypes, with the development and severity
      of erosions by five years in patients with IP. METHODS: 438 patients from the
      NOAR inception cohort of patients with IP were x rayed five years after
      presentation with early IP. Association with four exonic SNPs (padi4_89*G/A,
      padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and
      defining a haplotype previously reported to be associated with rheumatoid
      arthritis, was investigated. Patients were compared for the presence, extent, and
      progression of erosions by five years and the presence of antibodies to
      citrullinated peptide (anti-CCP antibodies). RESULTS: There was no association
      between individual PADI4 SNPs or haplotypes and the development or extent of
      erosions by five years. Restricting analysis to patients who satisfied ACR
      criteria for rheumatoid arthritis by five years did not alter the conclusions. No
      association with presence of anti-CCP antibodies was detected. CONCLUSIONS: No
      evidence was found for association of the PADI4 gene with severity as assessed by
      erosive outcome at five years or with presence of anti-CCP antibodies in patients
      with IP.

PMID- 15731288
TI  - Contribution of tumour necrosis factor alpha and interleukin (IL) 1beta to IL6
      production, NF-kappaB nuclear translocation, and class I MHC expression in muscle
      cells: in vitro regulation with specific cytokine inhibitors.
AB  - OBJECTIVE: To evaluate the effect of tumour necrosis factor alpha (TNFalpha),
      interleukin (IL) 1beta, and their respective inhibitors the p75 TNFalpha soluble
      receptor (sTNFR) and the type II sIL1betaR (sIL1RII) on whole muscle and isolated
      myoblast activation. METHODS: Normal muscle samples were stimulated for 7 days
      with TNFalpha alone or in combination with IL1beta, and myoblasts from these
      samples for 48 hours. IL6 production was measured by ELISA. Nuclear translocation
      of NF-kappaB was analysed by immunofluorescent staining and class I MHC
      expression by FACS. RESULTS: TNFalpha and IL1beta induced IL6 production by
      normal muscle samples and myoblasts, the action of TNFalpha being more potent on
      muscle samples. Their soluble receptors (1 microg/ml) decreased this production.
      Suboptimal concentrations of TNFalpha and IL1beta induced NF-kappaB
      translocation. sTNFR markedly down regulated TNFalpha-induced translocation while
      sIL1RII was less potent on IL1beta-induced activation. NF-kappaB translocation
      induced by the combination of optimal concentrations of TNFalpha and IL1beta was
      completely inhibited by their soluble receptors. TNFalpha and to a lesser extent
      IL1beta induced class I MHC expression by myoblasts and this effect was
      completely inhibited by their respective soluble receptors. CONCLUSION: These
      results suggest that TNFalpha and IL1beta should be targeted for myositis
      treatment.

PMID- 15731289
TI  - Markers of inflammation are negatively correlated with serum leptin in rheumatoid
      arthritis.
AB  - BACKGROUND: Leptin regulates food intake and modulates immunity and inflammation.
      A positive feedback mechanism has been described between tumour necrosis factor
      (TNF) and leptin, and it has been suggested that leptin potentiates inflammation
      in patients with rheumatoid arthritis (RA). OBJECTIVE: To assess whether
      inflammation correlates with leptin concentrations in patients with RA, and
      whether anti-TNF treatment modulates leptin concentrations in these patients.
      METHODS: Leptin, IL6 and CRP were measured (at baseline and after 2 weeks of
      treatment) in the blood of 31 patients with RA starting either anti-TNF treatment
      or placebo, and in 18 healthy controls. RESULTS: In patients with RA, plasma
      leptin concentrations at baseline correlated inversely with the degree of
      inflammation as assessed by C reactive protein (CRP; r(s)(2) = 0.21, p<0.01) or
      interleukin (IL) 6 concentrations (r(s)(2) = 0.22, p<0.008). Mean (SD) leptin
      concentrations did not differ between patients with RA and controls (6.0 (4.6) v
      4.2 (2.8) ng/ml in men; 15.1 (7.9) v 13.4 (5.2) ng/ml in women). Short course
      anti-TNF treatment for 2 weeks did not modify leptin concentrations, despite
      significant reduction of CRP and IL6. CONCLUSION: A significant inverse
      correlation between inflammation and leptin concentrations was found in patients
      with active RA, although plasma leptin concentrations did not significantly
      differ from those in healthy controls. This suggests that active chronic
      inflammation may lower plasma leptin concentrations. Two weeks' treatment with
      anti-TNF did not change plasma leptin concentrations and longer treatment may be
      needed to see an effect on leptin.

PMID- 15731290
TI  - Real world experience with antiphospholipid antibody tests: how stable are
      results over time?
AB  - OBJECTIVE: To determine the stability and the degree of variation of
      antiphospholipid antibody (aPL) results over time in a large cohort of well
      evaluated aPL positive patients; and to analyse factors contributing to aPL
      variation and the validity of aPL in a real world setting in which aPL tests are
      done in multiple laboratories. METHODS: The clinical characteristics, drug
      treatment, and 1652 data points for lupus anticoagulant (LA), anticardiolipin
      antibodies (aCL), and anti-beta2 glycoprotein I antibodies (anti-beta2GPI) were
      examined in 204 aPL positive patients; 81 of these met the Sapporo criteria for
      antiphospholipid syndrome (APS) and 123 were asymptomatic bearers of aPL.
      RESULTS: 87% of initially positive LA results, 88% of initially negative to low
      positive aCL results, 75% of initially moderate to high positive aCL results, 96%
      of initially negative to low positive anti-beta2GPI results, and 76% of initially
      moderate to high positive anti-beta2GPI results subsequently remained in the same
      range regardless of the laboratory performing the test. Aspirin, warfarin, and
      hydroxychloroquine use did not differ among patients whose aCL titres
      significantly decreased or increased or remained stable. On same day specimens,
      the consistency of aCL results among suppliers ranged from 64% to 88% and the
      correlation ranged from 0.5 to 0.8. Agreement was moderate for aCL IgG and aCL
      IgM; however, for aCL IgA agreement was marginal. CONCLUSIONS: aPL results
      remained stable for at least three quarters of subsequent tests, regardless of
      the laboratory performing the test; the small amount of variation that occurred
      did not appear to be caused by aspirin, warfarin, or hydroxychloroquine use.

PMID- 15731291
TI  - Efficacy of cyclo-oxygenase-2 inhibition by etoricoxib and naproxen on the axial
      manifestations of ankylosing spondylitis in the presence of peripheral arthritis.
AB  - OBJECTIVE: The combined efficacy of selective and non-selective cyclo-oxygenase-2
      (COX-2) inhibition on the axial manifestations of ankylosing spondylitis (AS) in
      the presence or absence of chronic peripheral arthritis was evaluated. METHODS:
      In a post hoc subgroup analysis of a 6 week, randomised, double blind, placebo
      controlled trial, 387 patients with active axial AS were randomised to receive
      etoricoxib 90 mg or 120 mg once a day, naproxen 500 mg twice daily, or placebo.
      Randomisation was stratified by the presence or absence of chronic peripheral
      arthritis. The primary outcome measure was the time weighted average change from
      baseline of spine pain intensity. Efficacy data from the three groups receiving
      active treatment (the NSAID/COX-2 inhibitor group) were combined to improve
      precision. An analysis of covariance model was used to evaluate the effect of
      peripheral disease on treatment response. RESULTS: 93 patients were allocated to
      receive placebo and 294 to active treatment (naproxen or etoricoxib). The
      combined NSAID/COX-2 inhibitor group had a significant treatment response
      compared with the placebo group for all efficacy measures, both in patients with
      and without peripheral arthritis. A significantly greater difference in mean
      patient assessment of spine pain was found between active and placebo treatments
      in patients without compared with those with peripheral arthritis (p = 0.005; 
      32.5 mm v -17.0 mm, respectively). Similar differences, although not
      statistically significant, were seen for other end points. CONCLUSION: NSAIDs and
      COX-2 inhibitors have a clinically relevant symptomatic effect on axial AS
      irrespective of the presence of peripheral arthritis. In this exploratory
      analysis spinal improvement appeared to be greater in patients without peripheral
      disease.

PMID- 15731293
TI  - Amphetamine induces apoptosis of medium spiny striatal projection neurons via the
      mitochondria-dependent pathway.
AB  - Amphetamine (AMPH) is a psychostimulant whose chronic abuse may cause impairments
      in attention and memory in humans. These cognitive deficits might be related to
      neurotoxic effects of the drug. One such toxic effect is the well-described
      destruction of striatal dopaminergic terminals in mammals. In the present study,
      we investigated the possibility that AMPH might also cause neuronal apoptosis in
      the rodent striatum. Administration of a dose of the drug (10 mg/kg, 4 times,
      every 2 h) that is toxic to dopaminergic terminals resulted in the appearance of
      striatal cells that were positive for cleaved caspase-3 and for terminal
      deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL),
      observations that are indicative of an ongoing apoptotic process. Dual
      immunofluorescence staining revealed that cleaved caspase-3-positive cells
      express calbindin and DARPP-32, but not somatostatin, parvalbumin, or cholinergic
      markers. In addition, AMPH also caused increased expression of p53 and Bax at
      both transcript and protein levels; in contrast, Bcl-2 levels were decreased
      after the AMPH injections. Moreover, Bax knockout mice showed resistance to AMPH
      induced apoptotic cell death but not to AMPH-induced destruction of dopaminergic
      terminals. When taken together, these observations indicate that injections of
      doses of AMPH that are known to destroy striatal dopamine terminals can also
      cause apoptotic death of postsynaptic medium spiny projection neurons via
      mitochondria-dependent mechanisms.

PMID- 15731294
TI  - Hepatotoxicity of alcohol-induced polar retinol metabolites involves apoptosis
      via loss of mitochondrial membrane potential.
AB  - Chronic alcohol consumption depletes hepatic vitamin A stores. However, vitamin A
      supplementation is hepatotoxic, which is further potentiated by concomitant
      alcohol consumption. It was suggested that polar retinol metabolites generated by
      alcohol-inducible cytochrome P4502E1 aggravate liver damage. However,
      experimental evidence supporting this hypothesis is lacking. To elucidate the
      effects of polar retinol metabolites on cultured HepG2 cells and primary rat
      hepatocytes, polar retinol metabolites were extracted from liver tissues of rats
      fed either an alcoholic or isocaloric control Lieber-DeCarli diet. Cell toxicity
      assays included morphology assessment, trypan blue exclusion test, and LDH/AST
      leakage. Staining for DAPI and acridine orange, FACS analysis, and Western blot
      for cleaved caspase-9 and -3 were used to detect apoptosis. Polar retinol
      metabolites caused marked cytotoxicity in a concentration- and time-dependent
      manner in both cell types reflected by morphological changes, a dramatic increase
      in trypan blue positive cells, and LDH/AST leakage. Toxicity was due to
      apoptosis, as demonstrated by a time-dependent increase of sub-G1 cellular
      events, a rapid loss of mitochondrial membrane potential, and a time-dependent
      activation of caspase-9 and -3. No toxicity was found with equivalent doses of
      the control extract from nonalcoholic rats. We demonstrate that polar retinol
      metabolites cause marked hepatocyte death through the induction of apoptosis.

PMID- 15731292
TI  - Synovial tissue inflammation in early and late osteoarthritis.
AB  - OBJECTIVE: To compare selected immunohistological features of inflammation in
      synovial tissue from patients with early and late osteoarthritis (OA). METHODS:
      Synovial tissue samples were obtained from 10 patients with knee pain, normal
      radiographs, and arthroscopic manifestations of OA (early OA), and from 15
      patients with OA undergoing knee joint arthroplasty (late OA). Conventional
      immunohistochemical techniques were used to measure microscopic manifestations of
      inflammation. The inflammatory cell infiltrate, blood vessel formation, and
      angiogenic factors, NF-kappaB activation, expression of tumour necrosis factor
      alpha (TNFalpha) and interleukin 1beta (IL1beta), and the presence of cyclo
      oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS)
      were isolated from early and late OA tissue samples to compare in vitro
      production of prostaglandin E2 (PGE2) RESULTS: Synovial tissue from patients with
      early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001)
      cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth
      factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001).
      Numbers of cells producing TNFalpha and IL1beta were also significantly greater
      in early OA (p<0.001). Manifestations of inflammation in early OA were associated
      with increased expression of the NF-kappaB1 (p<0.001) and RelA (p = 0.015)
      subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2
      production by cultured FLS was similar in both groups. CONCLUSION: Increased
      mononuclear cell infiltration and overexpression of mediators of inflammation
      were seen in early OA, compared with late OA. Isolated FLS were functionally
      similar in both groups, consistent with microenvironmental differences in the
      synovial tissue during different phases of OA. These observations may have
      important therapeutic implications for some patients during the early evolution
      of OA.

PMID- 15731295
TI  - The role of HOX genes in human implantation.
AB  - The endometrium undergoes an ordered process of differentiation leading to
      receptivity to embryonic implantation. HOX genes direct this development in a
      fashion similar to that in which they direct embryonic development, including
      development of the reproductive tract. HOXA10 and HOXA11 expression increases
      during the menstrual cycle, increasing drastically in the midluteal phase, at the
      time of implantation. This expression is regulated by sex steroid hormones. This
      expression is necessary for implantation of the blastocyst as demonstrated by the
      decreased implantation rates in women with altered HOX expression. HOX genes are
      markers of endometrial receptivity. The possibility of augmenting HOX gene
      expression with gene therapy to improve implantation has promise for the future.

PMID- 15731296
TI  - The vascular cast of the human uterus: from anatomy to physiology.
AB  - The blood supply to the uterus originates mainly from the uterine artery.
      However, the uterine and ovarian arteries form anastomoses bilaterally.
      Controversy exists about the direction of the flow in the anastomoses and thus
      the origin of the arterial supply to the tube and tubal part of the uterus. A
      similar arcade is formed by the vaginal and uterine arteries. We have
      investigated the vascular border of supply between the uterine and ovarian
      arteries in postmenopausal women, which was positioned in the uterus 1-2 cm from
      the tube. A similar result was found in younger, ovulating women. However, the
      border between the territories irrigated by the uterine and ovarian arteries
      differs between the follicular and luteal phase; more uterine tissue is perfused
      from the ovarian artery when a large follicle is present. This constitutes the
      first description of a functionally determined shift in the territorial divide of
      two vascular systems and has numerous practical implications. The venous system
      copies the arterial one with one major exception: some of the uterine veins join
      the ovarian outlet. The close contact between veins and arteries facilitates
      transfer of substances, thus forming semilocal systems of regulation; for
      example, the ovary locally influences the function of the ipsilateral tube and
      part of the uterus. From a therapeutic point of view, it has been documented that
      application of progesterone to the vagina creates high uterine concentrations due
      to local vascular transfer.

PMID- 15731297
TI  - Endometrial angiogenesis: from physiology to pathology.
AB  - Numerous factors have been implicated in angiogenesis. This article concentrates
      on the expression of the major angiogenic factors, namely, vascular endothelial
      growth factor (VEGF) and the angiopoietins in the human endometrium. Particular
      emphasis is placed on the expression of the angiopoietins and their physiological
      and pathological expression.

PMID- 15731298
TI  - Mechanisms underlying "functional" progesterone withdrawal at parturition.
AB  - Progesterone is a major factor maintaining uterine quiescence throughout
      pregnancy. In most species, peripheral progesterone levels decline before
      initiation of labor, and treatments that inhibit progesterone synthesis or action
      cause termination of pregnancy and/or premature deliveries. These findings
      suggest that progesterone withdrawal is required for activation of myometrial
      contractions. However, in humans, circulating progesterone levels remain elevated
      until birth, which leads to the notion that a "functional" progesterone
      withdrawal occurs before parturition. The apparent loss of progesterone
      sensitivity at term could be a consequence of several different mechanisms
      including: (1) the catabolism of progesterone in the uterus into inactive
      compounds; (2) alterations in progesterone receptor (PR) isoform ratios; (3)
      changes in cofactor protein levels affecting PR transactivation; and (4)
      inflammation-induced trans-repression of PR by nuclear factor kappaB. All of
      these mechanisms are potentially capable of decreasing uterine progesterone
      responsiveness at term, thus enabling the expression of pathways that originally
      were blocked by progesterone in early pregnancy. However, the specific uterine
      genes whose transcription is directly controlled by PR, and thus affected by
      "functional" progesterone withdrawal, remain to be identified.

PMID- 15731300
TI  - The patterns of uterine contractility in normal menstruating women: from
      physiology to pathology.
AB  - The nonpregnant uterus shows uterine activity throughout the menstrual cycle.
      This uterine activity was detected both by single strep tissue and by using
      intrauterine pressure recordings in vitro and in vivo. Today, ultrasound has made
      it possible to study this activity with a noninvasive approach and to assess
      uterine contractions (UCs) in real-time movements of the uterus. Throughout the
      menstrual cycle, wavelike activity patterns of the reproductive organ were
      established. These patterns are under control of steroid hormones. Adequate UCs
      may provide for gamete/embryo transportation throughout the uterotubal cavities
      and successful embryo implantation in spontaneous and/or assisted reproduction.
      Inadequate UCs may produce ectopic pregnancy, miscarriages, retrograde bleeding
      with dysmenorrhea, and endometriosis.

PMID- 15731299
TI  - Endocrine-immune interactions in human endometrium.
AB  - The immune system is a complex entity designed to eliminate foreign intruding
      antigens and is influenced by and, in turn, influences the function of the
      reproductive system. Despite the widespread associations between immunology and
      reproductive medicine, the study of system interactions remains in its infancy.
      Many diverse facts are accumulating, and pieces of the puzzle are becoming
      available to provide a clearer picture. In this review article, we focus on the
      interactions between endocrine and immune systems in the human endometrium.
      Understanding the molecular pathways in endocrine-immune interactions in the
      human endometrium is crucial to understand events such as menstrual bleeding,
      tissue repair and regeneration, inflammation, angiogenesis, blastocyst
      implantation, and progression of pregnancy. These events require a balanced
      regulation of endometrial differentiation, proliferation, cell survival,
      leukocyte recruitment, apoptosis, and angiogenesis by sex steroids. In this
      review, we first outline the role of survival factors such as phosphoinositol 3
      kinase/protein kinase B, PTEN, NFkappaB, and apoptotic molecules (Fas-FasL, Bcl
      2). We then discuss their regulation by estrogen and progesterone in the
      endometrium. We present evidence for direct and/or indirect roles of steroid
      hormones on the expression of chemotactic cytokines (interleukin-8 and monocyte
      chemotactic protein-1) and on the survival versus apoptosis of resident
      endometrial cells (stromal, epithelial, and endothelial cells) and nonresident
      cells (leukocytes).

PMID- 15731301
TI  - Myomas, pregnancy outcome, and in vitro fertilization.
AB  - Uterine fibroids have been reported in 27% of infertile women, and 50% of women
      with unexplained infertility become pregnant after myomectomy. The age at which a
      first pregnancy occurs is increasing from the thirties to the forties. This
      increase and the recurrence rate of leiomyomas from 15 to 30% points to the
      effect of myomas on the infertility. Mechanisms by which myomas may cause
      infertility are abnormal uterine contractility, elongation of the uterine cavity,
      and distortion of uterine vascularization. Surgery may have beneficial or adverse
      effects without clear data on its effect on the assisted reproductive technology
      (ART) procedures. The present study was undertaken to establish the impact of
      surgical removal of myomas on fertility and infertility of patients undergoing
      ART procedures. Patients who underwent surgical removal of myomas before in vitro
      fertilization (Group A) had a cumulative success rate of 33% for one to three
      procedures (28 clinical pregnancies in 84 patients) and delivery rate of 25% (21
      live births in 84 patients). Patients who underwent in vitro fertilization
      without previous surgery (Group B) had a 15% clinical pregnancy rate (13
      pregnancies in 84 patients) (P < 0.05) and 12% delivery rate (10 deliveries in 84
      pregnancies) (P < 0.05). Abortion rates were 7% (8 deliveries in 84 patients) and
      4% (3 deliveries in 84 patients) in Groups A and B, respectively. This study
      confirms the beneficial effect of surgical removal of fibroids before undergoing
      ART procedures.

PMID- 15731302
TI  - Number of transferred embryos: how to reduce multiple pregnancies.
AB  - Because the diagnostic tools for predicting whether an early cleavage stage
      embryo can lead to a viable pregnancy are still elusive, transfer of more than
      one embryo remains quite common. However, the only way to reduce multiple
      pregnancies, considered as the main adverse effect of assisted reproductive
      technology, is to transfer a single embryo. In countries such as Switzerland and
      Germany, the law allows cryopreservation only at the 2-pronuclear stage. This
      restricts considerably the possibility of selecting the embryos to be
      transferred. Therefore, a good cryopreservation program at the 2-pronuclear stage
      is an essential tool to optimize the efficiency of in vitro fertilization (IVF).
      We therefore recommend the Cumulated Singleton Delivery Rate (CUSIDERA) as a
      measure of standard IVF efficiency. This rate averages approximately 23.5% when
      calculated over the last 10 years in our unit and reaches a value above 35% for
      patients with more than 10 zygotes. Elective single-embryo transfers and the
      decrease of iatrogenic multiple pregnancies in IVF remain dependent on better
      prognostic tools for the appropriate selection of patients, gametes, and zygotes.

PMID- 15731303
TI  - Science and biotechnology: attempts of reconciliation.

PMID- 15731304
TI  - Assisted reproductive technologies in europe encompass diverse and complex
      ethical viewpoints: issues to be considered in reporting research in human
      reproduction.
AB  - The many dimensions of the field of reproduction (clinical, scientific, social,
      ethical, legal) must be addressed by those with editorial responsibility for the
      major journals in the field. As the editorial team of the leading reproductive
      journal Human Reproduction, we have evolved processes that attempt to ensure a
      transparent but robust approach to complexities whose impact varies across
      international boundaries.

PMID- 15731305
TI  - Aging of oocyte, ovary, and human reproduction.
AB  - We review age-related changes in the ovary and their effect on female fertility,
      with particular emphasis on follicle formation, follicle dynamics, and oocyte
      quality. The evidence indicates that the developmental processes leading to
      follicle formation set the rules determining follicle quiescence and growth. This
      regulatory system is maintained until menopause and is directly affected in at
      least some models of premature ovarian failure (POF), most strikingly in the
      Foxl2 mouse knockout, a model of human POF with monogenic etiology
      (blepharophimosis/ptosis/epicanthus inversus syndrome). Several lines of evidence
      indicate that if the ovarian germ cell lineage maintains regenerative potential,
      as recently suggested in the mouse, a role in follicle dynamics for germ stem
      cells, if any, is likely indirect or secondary. In addition, age-related
      variations in oocyte quality in animal models suggest that reproductive
      competence is acquired progressively and might depend on parallel growth and
      differentiation of follicle cells and stroma. Genomewide analyses of the mouse
      oocyte transcriptome have begun to be used to systematically investigate the
      mechanisms of reproductive competence that are altered with aging. Investigative
      and therapeutic strategies can benefit from considering the role of continuous
      interactions between follicle cells and oocytes from the beginning of
      histogenesis to full maturation.

PMID- 15731306
TI  - What criteria for the definition of oocyte quality?
AB  - Although the spermatozoon provides an essential contribution to the generation of
      a new individual, the developmental fate of the embryo is principally dictated by
      the oocyte. Oocyte competencies are acquired throughout oogenesis, via the
      interaction with somatic cells. The ability to reinitiate the meiotic process and
      undergo preimplantation development is progressively determined during the antral
      phase. It is known that these changes involve the nuclear and cytoplasmic
      compartments, respectively, but the underlying cellular and molecular mechanisms
      are still poorly understood. Analysis of various aspects of oocyte morphology
      (cytoplasm, zona pellucida, and polar body) via conventional phase-contrast
      microscopy has generated contrasting evidence on the possibility of establishing
      reliable criteria for the prediction of developmental potential. The introduction
      of a newly developed microscopy technique based on the detection of polarized
      light generated by birefringent cell structures has offered the possibility of
      visualizing noninvasively the meiotic spindle, whose presence is critical for
      fertilization and later developmental stages. However, further studies are needed
      to standardize and interpret the information accessible through such a technique.
      Although unable to preserve cell viability and therefore provide a method by
      which to select oocytes with superior developmental competence, invasive
      techniques can make a fundamental contribution to defining objective criteria of
      oocyte quality. In particular, immunofluorescence analysis, which is able to
      identify critical anomalies of the meiotic spindle and cytoskeleton organization
      that can account for oocyte quality, is an important method for assessing the
      efficiency of in vitro maturation systems.

PMID- 15731307
TI  - Hatching: how to select the clinical indications.
AB  - Currently, most fertility centers around the world use assisted hatching (AH)
      techniques to help embryo release out of the zona pellucida (ZP) and thus
      increase the implantation rate. For the last 13 years, several retrospective and
      prospective studies, assessing AH in different clinical indications, have given
      disparate results, making the selection of patients or embryos in need of this
      treatment complex. The most relevant conclusion obtained so far is that AH has a
      beneficial effect in women with repeated failures of embryo implantation. The
      place of AH in clinical practice in comparison with other approaches has to be
      reevaluated based on the selection of viable embryos using strict morphometric
      criteria and/or prolonged culture up to the blastocyst stage. Finally, the
      potential value of AH for indications other than repeated failure has to be
      weighed carefully to make sure that AH does not reduce the chances of
      implantation.

PMID- 15731308
TI  - Molecular regulation of mullerian development by Hox genes.
AB  - HOX genes are a family of regulatory molecules that encode conserved
      transcription factors controlling aspects of morphogenesis and cell
      differentiation during normal embryonic development. All metazoans possess a
      common genetic system for embryonic patterning, and this system is also used in
      the reproductive tract. Hox genes are also expressed in the adult uterus. Hox
      genes are essential both for the development of mullerian tract in the embryonic
      period and adult function. Sex steroids regulate Hox gene expression during
      embryonic and endometrial development in the menstrual cycle. EMX2 and beta(3)
      integrin acting downstream of Hoxa10 gene are likely involved in both these
      developmental processes. This article reviews the role and molecular regulation
      of Hox genes in reproductive tract development.

PMID- 15731309
TI  - Determinants of endometrial receptivity.
AB  - Understanding the molecular changes that occur during the window of implantation
      is fundamental to our knowledge of human reproduction. Lately, the development of
      microarray technology has allowed this process to be studied from a global
      molecular perspective. In the last 2 years, researchers have focused their
      efforts on throwing light on the gene expression profile of the receptive
      endometrium. The genes hold the key to the development of the endometrium at any
      stage, and we have focused our work on the window of implantation. The four most
      recently published works in this field have revealed a long list of genes that
      are up- or downregulated at the time of implantation. Although these studies have
      been conducted using varying approaches, collectively these studies identify new
      candidate markers that can be used to accurately diagnose the receptive state of
      the endometrium. The next step is to perform functional analysis for confirming
      the importance of these genes. In this article, we gather together these recent
      findings to provide an overview of the current knowledge regarding the genetic
      functioning of human endometrial receptivity and related processes.

PMID- 15731310
TI  - Leukemia inhibitory factor and human embryo implantation.
AB  - The success of embryonic implantation relies on an ideal cross-talk between the
      embryo and the receptive endometrium. This article focuses on the role of
      leukemia inhibitory factor (LIF) and its receptors in human embryo implantation.
      LIF is a secreted glycoprotein first described as a factor that induced the
      differentiation of mouse myeloid leukemic M1 cells into macrophages and later
      proposed as a marker of the embryo implantation process. An important role for
      LIF in implantation was shown on LIF knockout mice, when embryo implantation did
      not occur. In endometrium of healthy women, LIF and LIF mRNA are expressed
      throughout the menstrual cycle with a striking increase in the midsecretory
      phase, coinciding with a supposed window of implantation. Correlation in the
      expression of LIF and some other markers of implantation has been reported. LIF
      acts on cells by binding to the LIF receptor (LIFR) and gp130. Human blastocysts
      express mRNAs for LIFR and gp130, participating actively in establishing contact
      with the endometrium. In the endometrium, LIFR and gp130 are expressed in the
      endometrial epithelium throughout the cycle with strong increase in the
      midsecretory phase. Endometrium of infertile women produces significantly less
      LIF during the period of receptivity. The role of LIF gene mutations in
      unexplained infertility and implantation failures in IVF patients is not clear
      yet. Infertile patients showed reduced secretion of LIFR and gp130 compared with
      fertile controls during the implantation window. Recombinant human LIF might help
      to improve the implantation rate in women with unexplained infertility.

PMID- 15731311
TI  - Implantation failure in assisted reproduction technology and a critical approach
      to treatment.
AB  - In this article, we review the literature and our personal experience regarding
      the many factors that appear to influence implantation rate. Oocyte quality, as
      determined by patient age and aneuploidies, probably plays a major role in RIF.
      However, a panoply of other factors have been brought under investigation, quite
      often with contradictory results and additional intriguing questions to be
      studied. Infections of the vagina, cervix, and endometrium, the role of mucus
      aspiration and washing of the cervix on transfer, the role of catheter guidance
      for a correct transfer and potion of embryos, the effect of mock transfer, and
      the role of hysteroscopy and its timing before transfer procedures are analyzed
      both as a review of the literature and as opinions and data from our experience.
      Many of these factors are interlaced and from the apparently simple issue of
      trauma, to infections and immune modulation of hatching and implantation, a
      biological continuum can easily be identified. The impact of abnormalities of the
      immune system and of homeostasis abnormalities is also covered in a brief
      overview of reported works and our experience. These latter areas probably
      constitute the common biological background of all other external factors that,
      however, the skilled must equip themselves for improving implantation success.

PMID- 15731312
TI  - Effects of vaginal progesterone on pain and uterine contractility in patients
      with threatened abortion before twelve weeks of pregnancy.
AB  - Fifty women with previous diagnosis of inadequate luteal phase and threatened
      abortion underwent a prospective, randomized, double-blind study in one medical
      center carried out with a parallel trial. The primary objective was to establish
      the effects of vaginal progesterone (Crinone 8%) in reducing both pain and
      uterine contractions (UCs). The gel with or without (placebo) vaginal
      progesterone was administered once a day since the diagnosis of threatened
      abortion and for 5 days. The efficacy on pain symptom amelioration was evaluated
      by a 5-score intensity gradation, while the UCs were evaluated by ultrasound. The
      secondary objective of the study was to evaluate the outcome of the pregnancies.
      The use of progesterone was effective both on pain relief and on the frequency of
      the UCs that decreased after 5 days of vaginal progesterone administration (P <
      0.005). The evaluation of the ongoing pregnancy and spontaneous abortion in both
      study groups after 60 days showed that 4 patients of group A and 8 patients of
      group B miscarried (P < 0.05). In conclusion, patients with threatened abortion
      benefit from vaginal progesterone by a reduction of UCs and pain. The use of
      vaginal progesterone improved the outcome of pregnancies complicated by
      threatened abortion and previous diagnosis of inadequate luteal phase.

PMID- 15731313
TI  - Endometrial evaluation in superovulation programs: relationship with successful
      outcome.
AB  - It is well known that an adequate endometrial receptivity is required for
      successful implantation in both natural and assisted reproductive cycles. In
      particular, a brief "implantation window", during which endometrium undergoes
      anatomical and molecular changes necessary for embryo implantation, has been
      observed. The hormonal treatment applied to induce ovulation seems to be able to
      modify the normal development of the prenidatory endometrium, with possible
      negative effect on the implantation rate. For this reason, several attempts have
      been made to identify specific markers of endometrial receptivity, useful for
      predicting implantation outcome in clinical practice. Even if different
      histological, immunohistochemical, and ultrasonographic parameters are studied,
      none unfortunately has been univocally shown to be predictive of pregnancy
      outcome. Therefore, the evaluation of endometrial receptivity remains a challenge
      in clinical practice.

PMID- 15731314
TI  - Role of infection in in vitro fertilization treatment.
AB  - With the increasing demand for assisted reproductive techniques (ARTs), it is
      important to consider how to manage infection. Three main positive factors that
      contribute to successful in vitro fertilization (IVF) cycles are maternal age,
      the ovarian hyperstimulation protocol used, and the number and quality of
      transferred embryos. Negative factors include contamination and infection. This
      paper describes the issues relating to infection during IVF and proposes
      guidelines to control infection and to increase laboratory safety.

PMID- 15731315
TI  - Differential effects of lipopolysaccharide and thrombin on interleukin-8
      expression in syncytiotrophoblasts and endothelial cells: implications for fetal
      survival.
AB  - Syncytiotrophoblasts (SCTs) are directly bathed by maternal blood and, as such,
      are in direct contact with proinflammatory stimuli present in the maternal
      circulation. The extent and nature of cytokine responses induced in SCTs play a
      central role in the maintenance of pregnancy. Thrombin is a critical mediator of
      tissue factor-initiated blood coagulation. Thrombin has been more recently
      demonstrated to induce cytokine expression and inflammation in several cell
      types. To dissect the patterns of regulation of cytokine production in the
      placental villus, we compared the effects of thrombin and lipopolysaccharide
      (LPS) treatments on cytokine expression in SCTs and endothelial cells. For
      studies, primary cultures of cytotrophoblasts from human term placentas were
      differentiated to SCTs. We observed that the presence of thrombin only modestly
      enhanced interleukin-8 (IL-8) levels in SCTs in a manner that was not dose
      dependent. Conversely, SCTs were exquisitely sensitive to LPS, the presence of
      which induced approximately a 10-fold increase in IL-8 levels with an EC(50)
      approximately 1 ng/mL. Northern blotting and real-time PCR results indicated that
      LPS (but not thrombin) treatment induced a >4-fold increase in levels of IL-8
      mRNA. The addition of the anti-inflammatory steroid, dexamethasone, significantly
      reduced the LPS-mediated increase in levels of IL-8 in SCTs. Conversely, in human
      umbilical vein endothelial cells, thrombin and LPS treatments induced 10- and 20
      fold increases in IL-8 expression, respectively. These results indicate that LPS,
      but not thrombin, promotes proinflammatory processes in SCTs, with cell-type
      specificity. The inability of thrombin in the intervillous space to evoke
      inflammatory responses in SCTs may constitute an important aspect of fetal
      survival. Conversely, our results suggest that SCTs do play a key role in
      infection-associated changes in placental cytokine expression.

PMID- 15731316
TI  - Natural in vitro fertilization cycles.
AB  - Although the first in vitro fertilization (IVF) baby was born after a natural IVF
      cycle, very soon this procedure was almost abandoned mainly because of the very
      high cancellation rates, and controlled pharmacological ovarian hyperstimulation
      became the standard treatment in IVF cycles of normoresponder patients. However,
      in poor-responder patients, where only very few follicles can be recruited and
      very few oocytes, if any, can be retrieved after controlled ovarian
      hyperstimulation, natural IVF cycles may offer a comparable number of follicles,
      reduced costs, and less discomfort for the patients. In this group of patients,
      natural IVF cycle is a cost-effective approach.

PMID- 15731317
TI  - Artificial reproductive technology achievements for optimizing embryo quality.
AB  - Evaluation of morphological characteristics, to date, has been the most widely
      accepted method for the selection of embryos with higher developmental ability
      and optimization of the outcome of in vitro fertilization (IVF). Improvement in
      clinical results has also been pursued through attempts to generate embryos of
      high quality or to identify more reliable selection criteria. This work evaluates
      the possibility of improving embryo quality and subsequent IVF outcome in
      situations in which creation of supernumerary embryos is not allowed.
      Optimization of gamete selection and conditions of insemination, such as hormonal
      therapy to improve sperm quality of patients undergoing intracytoplasmic sperm
      injection treatment, use of power Doppler image for follicle selection, short
      coincubation of gametes during insemination, and use of a polscope for spindle
      detection, is described.

PMID- 15731318
TI  - New tools for optimizing endometrial receptivity in controlled ovarian
      hyperstimulation: aromatase inhibitors and LH/(mini)hCG.
AB  - In the long history of controlled ovarian hyperstimulation (COH), two steps stand
      out as being the most important ones for providing the high efficacy of current
      treatments: the introduction of GnRH agonists for the prevention of premature
      ovulation and the widespread use of pretreatment with oral contraceptives before
      COH for in vitro fertilization. Interestingly, the benefits of both measures
      resulted largely from pure serendipity, as the discovery of these advantages was
      mostly fortuitous and/or unintended. Today, we believe that two areas of research
      have the highest potential for further improving the efficacy of COH: (1)
      switching the follicle-stimulating hormone stimulus to that of luteinizing
      hormone (or small amounts of hCG) in the last stages of COH; and (2) using the
      benefit of the new third-generation aromatase inhibitors that have recently
      become available. The effects of the latter products are to enhance the
      endogenous production of gonadotropins (mostly FSH). This article reviews the
      background data and rationale that justifies each of these two new developments
      and summarizes data currently available.

PMID- 15731319
TI  - Number of embryos transferred and implantation.
AB  - Multiple pregnancies are considered the most frequent and serious complication of
      assisted reproduction technology. To reduce the frequency of multiple
      pregnancies, several centers have adopted a policy of reducing the number of
      embryos transferred in the uterus, suggesting single embryo transfer. Even though
      a significant number of papers have been published on this issue, no general
      consensus exists on how many embryos to replace in the uterus and at which
      cleavage stage. We conducted a retrospective study on cycles performed throughout
      2003, analyzing the relation between the number of embryos transferred and the
      pregnancy and implantation rates, evaluating also the role of the woman's age. No
      differences were found among the groups except in one-embryo transferred women,
      which were mostly natural cycles, for estradiol levels, number of mature oocytes
      retrieved, number of top quality embryos, and pregnancy rate. The implantation
      rate was significantly higher in the two-embryo transfers versus three-embryo
      transfers. We found higher pregnancy and implantation rates with similar multiple
      pregnancy rates in patients where only two embryos were transferred versus three
      embryos transfer when women were less than 35 years old. In women aged less than
      35 years, which in turn have the higher expectancy of successful pregnancy and
      also the higher risk of multiple pregnancy, the single embryo transfer is a
      suitable choice for these patients.

PMID- 15731320
TI  - Genetic basis of endometriosis.
AB  - Endometriosis is a complex gynecologic disorder that has long been recognized as
      showing heritable tendencies, with recurrence risks of 5-7% for first-degree
      relatives. Familial and epidemiologic studies support that this disease is a
      genetic disorder of polygenic/multifactorial inheritance. The current
      investigational challenge is to determine the number and location of causative
      genes. Recent advances in molecular technology make identification and
      elucidation of these genes now possible. In this review, we update previous
      communications in which we also reviewed heritability studies supporting
      polygenic/multifactorial inheritance, discuss the scientific basis of genomewide
      strategies for identifying causative genes, and identify potential candidate
      genes.

PMID- 15731321
TI  - Endometriosis and inflammation in infertility.
AB  - A wealth of publications proposes that endometriosis and inflammation may have an
      unfavorable influence on fertility. A recent meta-analysis of assisted
      reproductive technologies demonstrated that, once confounding factors are
      controlled for, the pregnancy rate in women with endometriosis is approximately
      50% of the rate of women with tubal factor infertility. Peritoneal fluid of women
      with endometriosis contains elevated amounts of macrophages and their secreted
      products, such as growth factors, cytokines, and angiogenic factors. Because
      reproductive organs are bathed in and thus will be influenced by peritoneal
      fluid, these proinflammatory mediators would affect various aspects of
      reproduction in women with endometriosis. Advanced stages of endometriosis may
      have easily understandable factors, such as distortion of the anatomy, causing
      infertility. On the other hand, in minimal or mild endometriosis mechanisms
      underlying reproductive failure are subtle and remain controversial. Recent
      reports suggest that inflammatory factors play a role in this endometriosis
      associated reproductive failure. This review provides an overview of recent data
      on the effects of endometriosis-associated inflammation on fertility.

PMID- 15731323
TI  - Surgical management of deeply infiltrating endometriosis: an update.
AB  - Deeply infiltrating endometriosis (DIE) manifests itself mainly in the form of
      pain, predominantly deep dyspareunia, and painful functional symptoms that are
      aggravated monthly during menstruation, with the semiology being directly
      correlated with the location of the lesions (bladder, rectum). A workup to assess
      the extent of the disease is necessary to establish an accurate map of the DIE
      lesions, which is the essential condition to perform complete exeresis. The
      treatment of first intention is surgical, because medical treatments are only
      palliative in the majority of cases. Successful treatment depends on achieving
      radical surgical exeresis. Analysis of the anatomical distribution of the DIE
      lesions allows a "surgical classification" to be proposed to standardize the
      modalities of surgical treatment. Further studies are needed to specify the place
      and modalities of medical treatments preoperatively and postoperatively.

PMID- 15731322
TI  - Future directions in endometriosis research.
AB  - Endometriosis is an important gynecological disease, pathologically defined by
      the ectopic presence of both endometrial glands and stroma, and clinically
      associated with pelvic pain and infertility. Our current knowledge of the
      pathogenesis, pathophysiology of related infertility, and spontaneous evolution
      is still limited, although endometriosis has been described for many years.
      Future research in endometriosis needs to focus on pathogenesis studies in the
      baboon model and on the early interactions between endometrial and peritoneal
      cells in the pelvic cavity at the time of menstruation. Proteomic and genomic
      approaches are needed to detect potential differences between eutopic endometrium
      and myometrium in women with and without endometriosis. Immunomodulatory drugs
      inhibiting endometriosis-associated pelvic inflammation may offer new medical
      treatment for endometriosis in the future.

PMID- 15731324
TI  - Uterine peristaltic activity and the development of endometriosis.
AB  - Peristaltic activity of the nonpregnant uterus serves fundamental functions in
      the early process of reproduction, such as directed transport of spermatozoa into
      the tube ipsilateral to the dominant follicle, high fundal implantation of the
      embryo, and, possibly, retrograde menstruation. Hyperperistalsis of the uterus is
      significantly associated with the development of endometriosis and adenomyosis.
      In women with hyperperistalsis, fragments of basal endometrium are detached
      during menstruation and transported into the peritoneal cavity. Fragments of
      basal endometrium have, because of their equipment with estrogen and progesterone
      receptors and because of their ability to produce estrogen, an increased
      potential of implantation and proliferation, resulting in pelvic endometriosis.
      In addition, hyperperistalsis induces the proliferation of basal endometrium into
      myometrial dehiscencies. This results in endometriosis-associated adenomyosis
      with a prevalence of approximately 90%. Adenomyosis results in impaired directed
      sperm transport and thus constitutes an important cause of sterility in women
      with endometriosis. Our own date and that from the literature strongly suggest
      that the principal mechanism of endometriosis/adenomyosis is the paracrine
      interference of endometrial estrogen with the cyclical endocrine control of
      archimyometrial peristalsis exerted by the ovary, thus resulting in
      hyperperistalsis.

PMID- 15731325
TI  - Subarachnoid analgesia in advanced labor: a comparison of subarachnoid analgesia
      and pudendal block in advanced labor: analgesic quality and obstetric outcome.
AB  - Pain control during labor is a primary objective of antalgic therapy. The use of
      the peridural as an elective procedure for labor analgesia is now corroborated by
      the international scientific community. Sometimes a combined spinal-peridural
      procedure is used together with the intrathecal administration of opioids to also
      cover the first stage of labor. Unfortunately, patients and/or gynecologists
      often request analgesia in a late stage of labor. The aim of our study was to
      evaluate the possibility of using a subarachnoid block alone for labor analgesia
      when this is requested at a late stage, that is, in advanced labor with cervical
      dilation greater than 7 cm. After approval by our ethics committee and the
      written and informed consent of the patients, 111 women were enrolled in this
      study and randomly divided into two groups. The first group (Group S: 55
      patients) received a subarachnoid block with 2.5 mg hyperbaric bupivacaine + 25
      mug fentanyl + 1 mL 10% glucose. A pudendal nerve block with 7 mL 2% mepivacaine
      in each side was administered to the second group (Group P: 56 patients). In both
      groups, careful maternal-fetal monitoring was conducted, and pain was scored on a
      numerical scale from 0 to 4, 10 minutes after placement of the block (time [T]
      0), at delivery (T1), and at episiorrhaphy (T2). In all patients, we recorded any
      side effects, the Apgar score at birth and after 5 minutes, the administration of
      other analgesic and/or sedative drugs, the degree of satisfaction, and the time
      of hospitalization after delivery. Evaluations were performed by
      anesthesiologists unaware of patients' treatment group. The duration of spinal
      analgesia was considered to be the time from injection of study drugs to the time
      of the patient's first request for additional analgesia. In no cases were there
      any side effects worthy of note, and hospitalization never exceeded 72 hours. The
      Apgar score was always between 7 and 10. All except one of the women in Group S
      were satisfied or more than satisfied with their pain management, whereas 50
      women in Group P expressed only moderate satisfaction or dissatisfaction (P <
      0.0001). In most patients in Group S, complete analgesia was obtained. In Group
      P, however, 10 minutes after placement of the pudendal nerve block, 40 patients
      reported no improvement in pain symptomatology during contractions and only 16
      reported less painful contractions (P < 0.0001). The duration of spinal analgesia
      (128 +/- 38 minutes) was enough in most cases for delivery to be completed. These
      results suggest that low-dose bupivacaine-fentanyl spinal analgesia represents an
      important option for pain relief in late labor, not the least because the
      procedure does not upset the dynamics of delivery or alter vital parameters and
      is welcomed by women in labor who are still able to collaborate actively in the
      birth of their baby.

PMID- 15731326
TI  - Obesity reduces the expression of GLUT4 in the endometrium of normoinsulinemic
      women affected by the polycystic ovary syndrome.
AB  - GLUT4 is the most important glucose transporter in insulin-dependent tissues. A
      decrease of its expression by the adipocytes was reported in polycystic ovary
      syndrome (PCOS), regardless of obesity and glucose tolerance. In PCOS, abnormal
      menstrual cycles, abnormal insulin secretory patterns, and obesity, which are
      risk factors for endometrial diseases, frequently coexist. The endometrial
      effects of insulin are direct through specific insulin receptors. However, it is
      unknown whether the endometrium expresses GLUT4 and can be considered an insulin
      regulated tissue. In this study, we investigated this question, and we
      investigated whether obesity modulates this expression in PCOS normoinsulinemic
      patients. We assayed GLUT4 in the endometrial samples from 18 normoinsulinemic
      PCOS patients and 9 controls in the advanced follicular phase of the cycle; 10
      patients were lean and 8 obese, and all were aged between 23 and 32 years. Most
      tissue was immediately frozen for RT-PCR; some tissue was saved for histology and
      immunohistochemistry. GLUT4 mRNA expression was measured in three samples for
      every patient and expressed as mean +/- SE of an arbitrary unit. In obese PCOS
      subjects, endometrial GLUT4 expression was significantly lower than in the lean
      ones (24.0 +/- 6.8 vs. 65.2 +/- 24.4; P < 0.005) and the controls (53.2 +/-
      10.7). Lean PCOS and control subjects showed similar values. GLUT4 immunostaining
      was strong in the epithelial and absent in the stromal cells. We demonstrated
      endometrial GLUT4 expression. The similar results in lean PCOS and control
      subjects suggest that endometrial GLUT4 expression is not affected by PCOS
      itself, whereas it is reduced by obesity in PCOS patients.

PMID- 15731327
TI  - A high-throughput screening of genes that encode proteins transported into the
      endoplasmic reticulum in mammalian cells.
AB  - The compartments of eukaryotic cells maintain a distinct protein composition to
      perform a variety of specialized functions. We developed a new method for
      identifying the proteins that are transported to the endoplasmic reticulum (ER)
      in living mammalian cells. The principle is based on the reconstitution of two
      split fragments of enhanced green fluorescent protein (EGFP) by protein splicing
      with DnaE from Synechocystis PCC6803. Complementary DNA (cDNA) libraries fused to
      the N-terminal halves of DnaE and EGFP are introduced in mammalian cells with
      retroviruses. If an expressed protein is transported into the ER, the N-terminal
      half of EGFP meets its C-terminal half in the ER, and full-length EGFP is
      reconstituted by protein splicing. The fluorescent cells are isolated using
      fluorescence-activated cell sorting and the cDNAs are sequenced. The developed
      method was able to accurately identify cDNAs that encode proteins transported to
      the ER. We identified 27 novel proteins as the ER-targeting proteins. The present
      method overcomes the limitation of the previous GFP- or epitope-tagged methods,
      using which it was difficult to identify the ER-targeting proteins in a high
      throughput manner.

PMID- 15731328
TI  - Selection of functional human antibodies from retroviral display libraries.
AB  - Antibody library technology represents a powerful tool for the discovery and
      design of antibodies with high affinity and specificity for their targets. To
      extend the technique to the expression and selection of antibody libraries in an
      eukaryotic environment, we provide here a proof of concept that retroviruses can
      be engineered for the display and selection of variable single-chain fragment
      (scFv) libraries. A retroviral library displaying the repertoire obtained after a
      single round of selection of a human synthetic scFv phage display library on
      laminin was generated. For selection, antigen-bound virus was efficiently
      recovered by an overlay with cells permissive for infection. This approach
      allowed more than 10(3)-fold enrichment of antigen binders in a single selection
      cycle. After three selection cycles, several scFvs were recovered showing similar
      laminin-binding activities but improved expression levels in mammalian cells as
      compared with a laminin-specific scFv selected by the conventional phage display
      approach. Thus, translational problems that occur when phage-selected antibodies
      have to be transferred onto mammalian expression systems to exert their
      therapeutic potential can be avoided by the use of retroviral display libraries.

PMID- 15731329
TI  - Simple and highly efficient BAC recombineering using galK selection.
AB  - Recombineering allows DNA cloned in Escherichia coli to be modified via lambda
      (lambda) Red-mediated homologous recombination, obviating the need for
      restriction enzymes and DNA ligases to modify DNA. Here, we describe the
      construction of three new recombineering strains (SW102, SW105 and SW106) that
      allow bacterial artificial chromosomes (BACs) to be modified using galK
      positive/negative selection. This two-step selection procedure allows DNA to be
      modified without introducing an unwanted selectable marker at the modification
      site. All three strains contain an otherwise complete galactose operon, except
      for a precise deletion of the galK gene, and a defective temperature-sensitive
      lambda prophage that makes recombineering possible. SW105 and SW106 cells in
      addition carry l-arabinose-inducible Cre or Flp genes, respectively. The galK
      function can be selected both for and against. This feature greatly reduces the
      background seen in other negative-selection schemes, and galK selection is
      considerably more efficient than other related selection methods published. We
      also show how galK selection can be used to rapidly introduce point mutations,
      deletions and loxP sites into BAC DNA and thus facilitate functional studies of
      SNP and/or disease-causing point mutations, the identification of long-range
      regulatory elements and the construction of conditional targeting vectors.

PMID- 15731330
TI  - Novel cyanine-AMP conjugates for efficient 5' RNA fluorescent labeling by one
      step transcription and replacement of [gamma-32P]ATP in RNA structural
      investigation.
AB  - Two novel fluorescent cyanine-AMP conjugates, F550/570 and F650/670, have been
      synthesized to serve as transcription initiators under the T7 phi2.5 promoter.
      Efficient fluorophore labeling of 5' RNA is achieved in a single transcription
      step by including F550/570 and F650/670 in the transcription solution. The
      current work makes fluorescently labeled RNA readily available for broad
      applications in biochemistry, molecular biology, structural biology and
      biomedicine. In particular, site-specifically fluorophore-labeled large RNAs
      prepared by the current method may be used to investigate RNA structure, folding
      and mechanism by various fluorescence techniques. In addition, F550/570 and
      F650/670 may replace [gamma-32P]ATP to prepare 5' labeled RNA for RNA structural
      and functional investigation, thereby eliminating the need for the unstable and
      radio-hazardous [gamma-32P]ATP.

PMID- 15731331
TI  - Multiplexed discovery of sequence polymorphisms using base-specific cleavage and
      MALDI-TOF MS.
AB  - The completion of the Human Genome Project provides researchers with a reference
      sequence that covers about 99% of the gene-containing regions and is more than
      99.9% accurate. Sequence drafts and completed sequences for several other species
      are also available to researchers worldwide. The ongoing effort to provide more
      and more genomic reference information now enables the detection of deviations
      from this 'genetic blueprint'. Comparative sequencing projects will play a major
      role in elucidating the meaning of the genetic code and in establishing a
      correlation between genotype and phenotype. As part of this effort, a number of
      projects will focus on distinct functional aspects, like resequencing of exons or
      HLA determining regions. Typically these target regions are short in length and
      their analysis does not require long read length. To find an efficient solution
      for these applications, we developed a novel method that allows simultaneous
      analysis of multiple independent target regions (Multiplexed Comparative Sequence
      Analysis) by employing base-specific cleavage biochemistry and MALDI TOF-MS
      analysis.

PMID- 15731332
TI  - Screening of retroviral cDNA libraries for factors involved in protein
      phosphorylation in signaling cascades.
AB  - We report a novel approach that allows for the rapid identification of proteins
      mediating phosphorylation in signaling cascades after specific stimulation. As a
      proof of concept, we used the interferon- gamma (IFN-gamma)-induced
      phosphorylation of signal transducer and activator of transcription-1 (Stat1) in
      a human promonocytic cell line, which was previously shown to be deficient in
      this signaling pathway. By using retroviral cDNA expression libraries, transduced
      selector cells expressing single cDNAs were stimulated with IFN-gamma, then
      fixed, permeabilized and stained intracellularly for phospho-Stat1 levels. Cells
      responding to the stimulation, which showed increased levels of phosphorylated
      Stat1, were enriched using fluorescence activated cell sorting (FACS). Genomic
      DNA was isolated from the enriched cell population and served as a template for
      cDNA amplification using PCR. After only one round of selection, a cDNA encoding
      the beta-chain of the IFN-gamma receptor (IFNGR2) was obtained and demonstrated
      to restore the selected phenotype. The approach now allows one to use phospho
      events as reporters, alone or in tandem, for screening of signaling network
      states, overcoming a prior need to rely on the reporter genes that are often only
      indirect measures of phenotypes desired in a screen.

PMID- 15731333
TI  - Modified branched peptides with a histidine-rich tail enhance in vitro gene
      transfection.
AB  - Successful gene therapy depends on the development of efficient, non-toxic gene
      delivery systems. To accomplish this objective, our laboratory has focused on
      solid-phase synthesized peptide carriers, in which the amino acid sequence can be
      varied precisely to augment intracellular DNA transport. We previously determined
      that linear and branched co-polymers of histidine and lysine in combination with
      liposomes enhanced the efficiency of gene transfection. In this study, we have
      modified two branched histidine-lysine (HK) peptides by adding a histidine-rich
      tail. In a variety of cell lines, this histidine-rich tail markedly improved
      transfection efficiency, presumably by increasing the buffering capacity of the
      polymer. One polymer with a histidine-rich tail, H2K4bT, compared favorably with
      the commonly used transfection agents. Together with modification of our
      transfection protocol, these improved HK peptides alone, without liposomes, are
      the effective carriers of plasmids into a variety of cells. We anticipate that
      branched HK peptides will continue to be developed as carriers of nucleic acids
      for in vitro and in vivo applications.

PMID- 15731334
TI  - Targeted 'knockdown' of spliceosome function in mammalian cells.
AB  - The existence of two sophisticated parallel splicing machineries in multicellular
      organisms has raised intriguing questions--ranging from their impact on proteome
      expansion to the evolution of splicing and of metazoan genomes. Exploring roles
      for the distinct splicing systems in vivo has, however, been restricted by the
      lack of techniques to selectively inhibit their function in cells. In this study,
      we show that morpholino oligomers complementary to the branch-site recognition
      elements of U2 or U12 small nuclear RNA specifically suppress the function of the
      two splicing systems in mammalian cells. The data provide the first evidence for
      a role of distinct spliceosomes in pre-mRNA splicing from endogenous mammalian
      genes and establish a tool to define roles for the different splicing machineries
      in vivo.

PMID- 15731335
TI  - A multipurpose vector system for the screening of libraries in bacteria, insect
      and mammalian cells and expression in vivo.
AB  - We have constructed a novel tetra-promoter vector (pBVboostFG) system that
      enables screening of gene/cDNA libraries for functional genomic studies. The
      vector enables an all-in-one strategy for gene expression in mammalian, bacterial
      and insect cells and is also suitable for direct use in vivo. Virus preparation
      is based on an improved mini Tn7 transpositional system allowing easy and fast
      production of recombinant baculoviruses with high diversity and negligible
      background. Cloning of the desired DNA fragments or libraries is based on the
      recombination system of bacteriophage lambda. As an example of the utility of the
      vector, genes or cDNAs of 18 different proteins were cloned into pBVboostFG and
      expressed in different hosts. As a proof-of-principle of using the vector for
      library screening, a chromophoric Thr65-Tyr-Gly67-stretch of enhanced green
      fluorescent protein was destroyed and subsequently restored by novel PCR strategy
      and library screening. The pBVboostFG enables screening of genome-wide libraries,
      thus making it an efficient new platform technology for functional genomics.

PMID- 15731336
TI  - Evolutionarily conserved human targets of adenosine to inosine RNA editing.
AB  - A-to-I RNA editing by ADARs is a post-transcriptional mechanism for expanding the
      proteomic repertoire. Genetic recoding by editing was so far observed for only a
      few mammalian RNAs that are predominantly expressed in nervous tissues. However,
      as these editing targets fail to explain the broad and severe phenotypes of ADAR1
      knockout mice, additional targets for editing by ADARs were always expected.
      Using comparative genomics and expressed sequence analysis, we identified and
      experimentally verified four additional candidate human substrates for ADAR
      mediated editing: FLNA, BLCAP, CYFIP2 and IGFBP7. Additionally, editing of three
      of these substrates was verified in the mouse while two of them were validated in
      chicken. Interestingly, none of these substrates encodes a receptor protein but
      two of them are strongly expressed in the CNS and seem important for proper
      nervous system function. The editing pattern observed suggests that some of the
      affected proteins might have altered physiological properties leaving the
      possibility that they can be related to the phenotypes of ADAR1 knockout mice.

PMID- 15731337
TI  - Translation of the first upstream ORF in the hepatitis B virus pregenomic RNA
      modulates translation at the core and polymerase initiation codons.
AB  - The human hepatitis B virus (HBV) has a compact genome encoding four major
      overlapping coding regions: the core, polymerase, surface and X. The polymerase
      initiation codon is preceded by the partially overlapping core and four or more
      upstream initiation codons. There is evidence that several mechanisms are used to
      enable the synthesis of the polymerase protein, including leaky scanning and
      ribosome reinitiation. We have examined the first AUG in the pregenomic RNA, it
      precedes that of the core. It initiates an uncharacterized short upstream open
      reading frame (uORF), highly conserved in all HBV subtypes, we designated the C0
      ORF. This arrangement suggested that expression of the core and polymerase may be
      affected by this uORF. Initiation at the C0 ORF was confirmed in reporter
      constructs in transfected cells. The C0 ORF had an inhibitory role in downstream
      expression from the core initiation site in HepG2 cells and in vitro, but also
      stimulated reinitiation at the polymerase start when in an optimal context. Our
      results indicate that the C0 ORF is a determinant in balancing the synthesis of
      the core and polymerase proteins.

PMID- 15731338
TI  - The effect of chemical modifications on the thermal stability of different G
      quadruplex-forming oligonucleotides.
AB  - A systematic study of the thermal and conformational properties of chemically
      modified G-quadruplexes of different molecularities is reported. The effect of
      backbone charge and atom size, thymine/uracyl substitution as well as the effect
      of modification at the ribose 2'-position was analyzed by UV spectroscopy.
      Additional calorimetric studies were performed on different modified forms of the
      human telomeric sequence. Determination of the differential spectra allowed more
      insights into the conformational properties of the oligonucleotides. Lack of
      negative charge at the phosphate backbone yielded to a general destabilization of
      the G-quadruplex structure. On the other hand, substitution of thymine with
      uracyl resulted in a moderate or strong stabilization of the structure.
      Additional modification at the sugar 2'-position gave rise to different effects
      depending on the molecularity of the quadruplex. In particular, loss of hydrogen
      bond capacity at the 2'-position strongly affected the conformation of the G
      quadruplex. Altogether, these results demonstrate that the effect of some
      modifications depends on the sequence context, thus providing helpful information
      for the use of chemically modified quadruplexes as therapeutic agents or as
      structural elements of supramolecular complexes.

PMID- 15731339
TI  - Separation of mutation avoidance and antirecombination functions in an
      Escherichia coli mutS mutant.
AB  - DNA mismatch repair in Escherichia coli has been shown to be involved in two
      distinct processes: mutation avoidance, which removes potential mutations arising
      as replication errors, and antirecombination which prevents recombination between
      related, but not identical (homeologous), DNA sequences. We show that cells with
      the mutSDelta800 mutation (which removes the C-terminal 53 amino acids of MutS)
      on a multicopy plasmid are proficient for mutation avoidance. In interspecies
      genetic crosses, however, recipients with the mutSDelta800 mutation show
      increased recombination by up to 280-fold relative to mutS+. The MutSDelta800
      protein binds to O6-methylguanine mismatches but not to intrastrand platinated GG
      cross-links, explaining why dam bacteria with the mutSDelta800 mutation are
      resistant to cisplatin, but not MNNG, toxicity. The results indicate that the C
      terminal end of MutS is necessary for antirecombination and cisplatin
      sensitization, but less significant for mutation avoidance. The inability of
      MutSDelta800 to form tetramers may indicate that these are the active form of
      MutS.

PMID- 15731340
TI  - Enhanced RNA cleavage within bulge-loops by an artificial ribonuclease.
AB  - Cleavage of phosphodiester bonds by small ribonuclease mimics within different
      bulge-loops of RNA was investigated. Bulge-loops of different size (1-7 nt) and
      sequence composition were formed in a 3' terminal fragment of influenza virus M2
      RNA (96 nt) by hybridization of complementary oligodeoxynucleotides. Small bulges
      (up to 4 nt) were readily formed upon oligonucleotide hybridization, whereas
      hybridization of the RNA to the oligonucleotides designed to produce larger
      bulges resulted in formation of several alternative structures. A synthetic
      ribonuclease mimic displaying Pyr-Pu cleavage specificity cleaved CpA motifs
      located within bulges faster than similar motifs within the rest of the RNA. In
      the presence of 10 mM MgCl2, 75% of the cleavage products resulted from the
      attack of this motif. Thus, selective RNA cleavage at a single target
      phosphodiester bond was achieved by using bulge forming oligonucleotides and a
      small ribonuclease A mimic.

PMID- 15731341
TI  - Structure and RNA binding of the third KH domain of poly(C)-binding protein 1.
AB  - Poly(C)-binding proteins (CPs) are important regulators of mRNA stability and
      translational regulation. They recognize C-rich RNA through their triple KH (hn
      RNP K homology) domain structures and are thought to carry out their function
      though direct protection of mRNA sites as well as through interactions with other
      RNA-binding proteins. We report the crystallographically derived structure of the
      third domain of alphaCP1 to 2.1 A resolution. alphaCP1-KH3 assumes a classical
      type I KH domain fold with a triple-stranded beta-sheet held against a three
      helix cluster in a betaalphaalphabetabetaalpha configuration. Its binding
      affinity to an RNA sequence from the 3'-untranslated region (3'-UTR) of androgen
      receptor mRNA was determined using surface plasmon resonance, giving a K(d) of
      4.37 microM, which is indicative of intermediate binding. A model of alphaCP1-KH3
      with poly(C)-RNA was generated by homology to a recently reported RNA-bound KH
      domain structure and suggests the molecular basis for oligonucleotide binding and
      poly(C)-RNA specificity.

PMID- 15731342
TI  - Human base excision repair enzymes apurinic/apyrimidinic endonuclease1 (APE1),
      DNA polymerase beta and poly(ADP-ribose) polymerase 1: interplay between strand
      displacement DNA synthesis and proofreading exonuclease activity.
AB  - We examined interactions between base excision repair (BER) DNA intermediates and
      purified human BER enzymes, DNA polymerase beta (pol beta), apurinic/apyrimidinic
      endonuclease (APE1) and poly(ADP-ribose) polymerase-1 (PARP-1). Studies under
      steady-state conditions with purified BER enzymes and BER substrates have already
      demonstrated interplay between these BER enzymes that is sensitive to the
      respective concentrations of each enzyme. Therefore, in this study, using
      conditions of enzyme excess over substrate DNA, we further examine the question
      of interplay between BER enzymes on BER intermediates. The results reveal several
      important differences compared with data obtained using steady-state assays.
      Excess PARP-1 antagonizes the action of pol beta, producing a complete block of
      long patch BER strand-displacement DNA synthesis. Surprisingly, an excess of APE1
      stimulates strand-displacement DNA synthesis by pol beta, but this effect is
      blocked by PARP-1. The APE1 exonuclease function appears to be modulated by the
      other BER proteins. Excess APE1 over pol beta may allow APE1 to perform both
      exonuclease function and stimulation of strand-displacement DNA synthesis by pol
      beta. This enables pol beta to mediate long patch sub-pathway. These results
      indicate that differences in the stoichiometry of BER enzymes may regulate BER.

PMID- 15731343
TI  - Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2.
AB  - The ends of linear chromosomes are capped by protein-DNA complexes termed
      telomeres. Telomere repeat binding factors 1 and 2 (TRF1 and TRF2) bind
      specifically to duplex telomeric DNA and are critical components of functional
      telomeres. Consequences of telomere dysfunction include genomic instability,
      cellular apoptosis or senescence and organismal aging. Mild oxidative stress
      induces increased erosion and loss of telomeric DNA in human fibroblasts. We
      performed binding assays to determine whether oxidative DNA damage in telomeric
      DNA alters the binding activity of TRF1 and TRF2 proteins. Here, we report that a
      single 8-oxo-guanine lesion in a defined telomeric substrate reduced the
      percentage of bound TRF1 and TRF2 proteins by at least 50%, compared with
      undamaged telomeric DNA. More dramatic effects on TRF1 and TRF2 binding were
      observed with multiple 8-oxo-guanine lesions in the tandem telomeric repeats.
      Binding was likewise disrupted when certain intermediates of base excision repair
      were present within the telomeric tract, namely abasic sites or single nucleotide
      gaps. These studies indicate that oxidative DNA damage may exert deleterious
      effects on telomeres by disrupting the association of telomere-maintenance
      proteins TRF1 and TRF2.

PMID- 15731344
TI  - Target-dependent on/off switch increases ribozyme fidelity.
AB  - Ribozymes, RNA molecules that catalyze the cleavage of RNA substrates, provide an
      interesting alternative to the RNA interference (RNAi) approach to gene
      inactivation, especially given the fact that RNAi seems to trigger an
      immunological response. Unfortunately, the limited substrate specificity of
      ribozymes is considered to be a significant hurdle in their development as
      molecular tools. Here, we report the molecular engineering of a ribozyme
      possessing a new biosensor module that switches the cleavage activity from 'off'
      (a 'safety lock') to 'on' solely in the presence of the appropriate RNA target
      substrate. Both proof-of-concept and the mechanism of action of this man-made
      riboswitch are demonstrated using hepatitis delta virus ribozymes that cleave RNA
      transcripts derived from the hepatitis B and C viruses. To our knowledge, this is
      the first report of a ribozyme bearing a target-dependent module that is
      activated by its RNA substrate, an arrangement which greatly diminishes non
      specific effects. This new approach provides a highly specific and improved tool
      with significant potential for application in the fields of both functional
      genomics and gene therapy.

PMID- 15731345
TI  - Reciprocal evolution of the cerebellum and neocortex in fossil humans.
AB  - Human brain evolution involved both neurological reorganization and an increase
      in overall brain volume relative to body mass. It is generally difficult to draw
      functional inferences about the timing and nature of brain reorganization, given
      that superficial brain morphology recorded on fossil endocasts is functionally
      ambiguous. However, the cerebellum, housed in the clearly delineated posterior
      cranial fossa, is functionally and ontologically discrete. The cerebellum is
      reciprocally connected to each of 14 neocortical regions important to human
      cognitive evolution. Cerebellar volume varies significantly relative to overall
      brain volume among mammalian orders, as well as within the primate order. There
      is also significant diachronic variation among fossil human taxa. In the
      australopithecines and early members of the genus Homo, the cerebral hemispheres
      were large in proportion to the cerebellum, compared with other hominoids. This
      trend continued in Middle and Late Pleistocene humans, including Neandertals and
      Cro-Magnon 1, who have the largest cerebral hemispheres relative to cerebellum
      volume of any primates, including earlier and Holocene humans. In recent humans,
      however, the pattern is reversed; the cerebellum is larger with respect to the
      rest of the brain (and, conversely, the cerebral hemispheres are smaller with
      respect to the cerebellum) than in Late Pleistocene humans. The cerebellum and
      cerebral hemispheres appear to have evolved reciprocally. Cerebellar development
      in Holocene humans may have provided greater computational efficiency for coping
      with an increasingly complex cultural and conceptual environment.

PMID- 15731346
TI  - Seeing the light: illumination as a contextual cue to color choice behavior in
      bumblebees.
AB  - The principal challenge faced by any color vision system is to contend with the
      inherent ambiguity of stimulus information, which represents the interaction
      between multiple attributes of the world (e.g., object reflectance and
      illumination). How natural systems deal with this problem is not known, although
      traditional hypotheses are predicated on the idea that vision represents object
      reflectance accurately by discounting early in processing the conflating effects
      of illumination. Here, we test the merits of this general supposition by
      confronting bumblebees (Bombus terrestris) with a color discrimination task that
      can be solved only if information about the illuminant is not discounted but
      maintained in processing and thus available to higher-order learned behavior. We
      show that bees correctly use the intensity and chromaticity of illumination as a
      contextual cue to guide them to different target colors. In fact, we trained bees
      to choose opposite, rather than most similar, target colors after an illumination
      change. This performance cannot be explained with a simple color-constancy
      mechanism that discounts illumination. Further tests show that bees do not use a
      simple assessment of the overhead illumination, but that they assess the spectral
      relationships between a floral target and its background. These results
      demonstrate that bees can be color-constant without discounting the illuminant;
      that, in fact, they can use information about the illuminant itself as a salient
      source of information.

PMID- 15731347
TI  - Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in
      enhanced apoptosis and defective neural tube development.
AB  - Neural tube defects (NTDs) are prevalent human birth defects. Mitogen-activated
      protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK), are implicated in
      facilitating neural tube closure, yet upstream regulators remain to be
      identified. Here, we show that MAP kinase kinase kinase 4 (MEKK4) is strongly
      expressed in the developing neuroepithelium. Mice deficient in MEKK4 develop
      highly penetrant NTDs that cannot be rescued by supplementation with folic acid
      or inositol. Unlike most mouse models of NTDs, MEKK4 mutant embryos display
      genetically co-segregated exencephaly and spina bifida, recapitulating the
      phenotypes observed in human patients. To identify downstream targets of MEKK4
      during neural tube development, we examined the activity of MAP kinase kinase 4
      (MKK4), a signaling intermediate between MAP kinase kinase kinase and JNK/p38. We
      found a significant reduction in MKK4 activity in MEKK4-deficient neuroepithelium
      at sites of neural tube closure. MAPK pathways are key regulators of cell
      apoptosis and proliferation. Analyses of the neuroepithelium in MEKK4-deficient
      embryos showed massively elevated apoptosis before and during neural tube
      closure, suggesting an antiapoptotic role for MEKK4 during development. In
      contrast, proliferation of MEKK4-deficient neuroepithelial cells appeared to be
      largely unaffected. MEKK4 therefore plays a critical role in regulating MKK4
      activity and apoptotic cell death during neural tube development. Disruption of
      this signaling pathway may be clinically relevant to folate-resistant human NTDs.

PMID- 15731349
TI  - A bifunctional DNA repair protein from Ferroplasma acidarmanus exhibits O6
      alkylguanine-DNA alkyltransferase and endonuclease V activities.
AB  - A recently discovered DNA repair protein of 303 aa from the archaeal organism
      Ferroplasma acidarmanus was studied. This protein (AGTendoV) consists of a fusion
      of the C-terminal active site domain of O(6)-alkylguanine-DNA alkyltransferase
      (AGT) with an endonuclease V domain. The AGTendoV recombinant protein expressed
      in Escherichia coli and purified to homogeneity repaired O(6)-methylguanine
      lesions in DNA via alkyl transfer action despite the complete absence of the N
      terminal domain and some differences in key active site residues present in known
      AGTs. The AGTendoV recombinant protein also cleaved DNA substrates that contained
      the deaminated bases uracil, hypoxanthine, or xanthine in a similar manner to E.
      coli endonuclease V. Expression of AGTendoV in E. coli GWR109, a strain that
      lacks endogenous AGT activity, protected against both the killing and mutagenic
      activity of N-methyl-N'-nitro-N-nitrosoguanidine and was more effective in
      preventing mutations than human alkyltransferase, suggesting that the
      endonuclease V activity may also repair a promutagenic lesion produced by this
      alkylating agent. Expression of AGTendoV in a DNA repair-deficient E. coli nfi(
      )alkA(-) strain protected from spontaneous mutations arising in saturated
      cultures and restored the mutation frequency to that found in the nfi(+) alkA(+)
      strain. These results demonstrate the physiological occurrence of two completely
      different but functional DNA repair activities in a single polypeptide chain.

PMID- 15731348
TI  - ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non
      small cell lung cancer cell lines.
AB  - Therapies that target the EGF receptor (EGFR), such as gefitinib (IRESSA), are
      effective in a subset of patients with advanced non-small cell lung cancer
      (NSCLC). The differences in intracellular signaling networks between gefitinib
      sensitive and -resistant NSCLCs remain poorly understood. In this study, we
      observe that gefitinib reduces phospho-Akt levels only in NSCLC cell lines in
      which it inhibits growth. To elucidate the mechanism underlying this observation,
      we compared immunoprecipitates of phosphoinositide 3-kinase (PI3K) between
      gefitinib-sensitive and -resistant NSCLC cell lines. We observe that PI3K
      associates with ErbB-3 exclusively in gefitinib-sensitive NSCLC cell lines.
      Gefitinib dissociates this complex, thereby linking EGFR inhibition to decreased
      Akt activity. In contrast, gefitinib-resistant cells do not use ErbB-3 to
      activate the PI3K/Akt pathway. In fact, abundant ErbB-3 expression is detected
      only in gefitinib-sensitive NSCLC cell lines. Two gefitinib-sensitive NSCLC cell
      lines with endogenous distinct activating EGFR mutations (L858R and Del747-749),
      frequently observed in NSCLC patients who respond to gefitinib, also use ErbB-3
      to couple to PI3K. Down-regulation of ErbB-3 by means of short hairpin RNA leads
      to decreased phospho-Akt levels in the gefitinib-sensitive NSCLC cell lines, Calu
      3 (WT EGFR) and H3255 (L858R EGFR), but has no effect on Akt activation in the
      gefitinib-resistant cell lines, A549 and H522. We conclude that ErbB-3 is used to
      couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines
      harboring WT and mutant EGFRs.

PMID- 15731350
TI  - The time course and specificity of perceptual deterioration.
AB  - Repeated within-day testing on a texture discrimination task leads to
      retinotopically specific decreases in performance. Although perceptual learning
      has been shown to be highly specific to the retinotopic location and
      characteristics of the trained stimulus, the specificity of perceptual
      deterioration has not been studied. We investigated the similarities between
      learning and deterioration by examining whether deterioration transfers to new
      distractor or target orientations or to the untrained eye. Participants performed
      a texture discrimination task in three one-hour sessions. We tested the
      specificity of deterioration in the final session by switching either the
      orientation of the background or the target elements by 90 degrees. We found that
      performance deteriorated steadily both within and across the first two sessions
      and was specific to the target but not the distractor orientation. In a separate
      experiment, we found that deterioration transferred to the untrained eye. Changes
      in performance were independent of reported sleepiness and awareness of stimulus
      changes, arguing against the possibility that perceptual deterioration is due to
      general fatigue. Rather, we hypothesize that perceptual deterioration may be
      caused by changes in the ability for attention to selectively enhance the
      responses of relatively low-level orientation-selective sensory neurons, possibly
      within the primary visual cortex. Further, the differences in specificity
      profiles between learning and deterioration suggest separate underlying
      mechanisms that occur within the same cortical area.

PMID- 15731351
TI  - The basic helix-loop-helix olig3 establishes the neural plate boundary of the
      trunk and is necessary for development of the dorsal spinal cord.
AB  - olig genes encode a previously unrecognized group of vertebrate-specific basic
      helix-loop-helix transcription factors. As shown in mice, chickens, and
      zebrafish, two members of this group, olig1 and olig2, are involved in the
      differentiation of motoneurons and oligodendrocytes, but nothing is known about
      the role of the third member, olig3. Here, we show that olig3 plays an essential
      role in the establishment of the neural crest-lateral neural plate boundary. In
      zebrafish embryos, morpholino-induced olig3 inactivation dramatically increases
      the number of neural crest cells, but lateral neural plate fates (interneurons
      and astrocytes) are missing. Zebrafish swirl mutants that have impaired bone
      morphogenetic protein signaling and lack neural crest cells display an expanded
      olig3 expression domain. Moreover, olig3 is up-regulated in mindbomb mutants
      lacking the neural crest because of an impaired notch signaling, and olig3
      repression in such mutants rescues the neural crest. In addition, olig3 regulates
      ngn1 and deltaA expression in interneuron precursors. Our results indicate that
      olig3 has an essential proneural activity in the dorsal spinal cord and
      cooperates with the Delta/Notch regulatory loop to establish the boundary between
      the neural crest and the lateral neural plate. Thus, a proper regulation of the
      olig gene family is essential for the formation of three cell types
      (oligodendrocytes, astrocytes, and neural crest) that are unique to vertebrates.

PMID- 15731352
TI  - Regulation of coactivator complex assembly and function by protein arginine
      methylation and demethylimination.
AB  - Nuclear receptors activate transcription by recruiting multiple coactivators to
      the promoters of specific target genes. The functional synergy of the p160
      coactivators [steroid receptor coactivator-1, glucocorticoid receptor interacting
      protein (GRIP1), or the activator for thyroid hormone and retinoid receptors],
      the histone acetyltransferases cAMP response element binding protein binding
      protein (CBP) and p300 and the histone methyltransferase coactivator-associated
      arginine methyltransferase (CARM1) depends on the methyltransferase activity of
      CARM1. CARM1 methylates histone H3 and other factors including the N-terminal
      region of p300. Here, we report that CARM1 also methylates Arg-2142 within the C
      terminal GRIP1 binding domain (GBD) of p300. In the GBD, both Arg-2088 and Arg
      2142 are important for binding GRIP1. Methylation of Arg-2142 inhibits the
      bimolecular interaction of GRIP1 to p300 in vitro and in vivo. This methylation
      mark of p300 GBD is removed by peptidyl deiminase 4, thereby enhancing the p300
      GRIP1 interaction. These methylation and demethylimination events also alter the
      conformation and activity of the coactivator complex and regulate estrogen
      receptor-mediated transcription, and they thus represent unique mechanisms for
      regulating coactivator complex assembly, conformation, and function.

PMID- 15731353
TI  - The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to
      viral and cellular antigens.
AB  - CD8+ T lymphocytes play a major role in cellular-mediated immune responses to
      foreign antigen. We have previously demonstrated that costimulation of purified
      human CD8+ T cells induces de novo expression of the CD4 molecule and that
      ligation of CD4 on this cell type modulates CD8+ T cell activity in vitro.
      Herein, we investigate how the CD4 molecule expressed on murine CD8+ T cells
      contributes to CD8+ cell responses in vivo by employing adoptive transfer of CD8
      cells from CD4 knockout mice into severe combined immunodeficient (SCID)
      recipients. Transfer of these cells into syngeneic SCID mice resulted in a
      decreased immune response to infection by lymphocytic choriomeningitis virus.
      These decreased responses occurred even in the presence of CD4+ T cells,
      indicating that this was truly a CD8-cell defect. Similarly, transfer of CD8+ T
      cells incapable of expressing CD4 into allogeneic SCID mice resulted in a
      decreased response to alloantigens compared with that of normal CD8+ T cells.
      Therefore, CD4 expression on CD8 T lymphocytes modulates cytotoxic T lymphocyte
      function and is critical in vivo for optimal cell-mediated immunity to viral and
      alloantigens.

PMID- 15731354
TI  - AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells,
      allowing nerve growth factor-induced expansion.
AB  - The AML1-ETO fusion protein, generated by the t(8;21) in acute myeloid leukemia
      (AML), exerts dominant-negative functions and a variety of gains of function,
      including a positive effect on the growth of primary human CD34+ hematopoietic
      stem/progenitor cells. We now show that AML1-ETO expression up-regulates the
      level of TRKA mRNA and protein in these cells and that AML1-ETO-expressing CD34+
      hematopoietic cells grown in the presence of five early-acting hematopoietic
      cytokines further proliferate in response to nerve growth factor (NGF). These
      cells also show a unique response to NGF and IL-3; namely, they expand in liquid
      culture. To determine the biological relevance of our findings, we analyzed 262
      primary AML patient samples using real-time RT-PCR and found that t(8;21)
      positive AML samples express significantly higher levels of TRKA mRNA than other
      subtypes of AML. NGF, which is normally expressed by bone marrow stromal cells,
      could provide important proliferative or survival signals to AML1-ETO-expressing
      leukemic or preleukemic cells, and the NGF/TRKA signaling pathway may be a
      suitable target for therapeutic approaches to AML.

PMID- 15731355
TI  - Structural polymorphism of the cytoskeleton: a model of linker-assisted filament
      aggregation.
AB  - The phase behavior of charged rods in the presence of interrod linkers is studied
      theoretically as a model for the equilibrium behavior underlying the organization
      of actin filaments by linker proteins in the cytoskeleton. The presence of
      linkers in the solution modifies the effective interrod interaction and can lead
      to interfilament attraction. Depending on the composition and physical properties
      of the system, such as linker-binding energies, filaments will orient either
      perpendicular or parallel to each other, leading to network-like or bundled
      structures. We show that such a system can have one of three generic phase
      diagrams, one dominated by bundles, another by networks, and the third containing
      both bundle and network-like phases. The first two diagrams can be found over a
      wide range of interaction energies, whereas the third diagram occurs only for a
      narrow range. These results provide theoretical understanding of the
      classification of linker proteins as bundling proteins or crosslinking proteins.
      In addition, they suggest possible mechanisms by which the cell may control
      cytoskeletal morphology.

PMID- 15731356
TI  - Development, maintenance, and function of the adrenal gland in early postnatal
      proopiomelanocortin-null mutant mice.
AB  - Adult mouse mutants homozygous for an engineered proopiomelanocortin (POMC)-null
      allele lack macroscopically distinct adrenal glands and circulating adrenal
      hormones. To understand the basis for this adrenal defect, we compared the
      development of adrenal primordia in POMC-null mice and littermate controls. POMC
      null mutant mice are born with adrenal glands that are morphologically
      indistinguishable from those of their wild-type littermates. However, in mutants
      adrenal cells fail to proliferate postnatally and adrenals atrophy until they
      have disappeared macroscopically in the adult. While present, mutant adrenals are
      differentiated as evidenced by the presence of enzymes for the final steps in the
      synthesis of corticosterone, aldosterone, and catecholamines. However, in
      contrast to adrenals of wild-type littermates, adrenals of POMC-null mutants do
      not produce corticosterone, not even in response to acute stimulation with
      exogenous ACTH. They do produce aldosterone; however, it is produced at reduced
      levels correlating with adrenal size. Transplantation of POMC-null mutant
      adrenals to adrenalectomized wild-type littermates results in adrenals with
      normal morphology and production of both corticosterone and aldosterone. These
      findings demonstrate that POMC peptides are not required for prenatal adrenal
      development and that POMC peptides in addition to ACTH are required for postnatal
      proliferation and maintenance of adrenal structures capable of producing both
      glucocorticoids and mineralocorticoids.

PMID- 15731357
TI  - In vitro growth and ovulation of follicles from ovaries of estrogen receptor
      (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular
      maturation.
AB  - Both estrogen receptor (ER) alpha and beta are expressed within the ovary and
      lack of either of these receptors affects ovarian function. In this study, the
      role of ERalpha and ERbeta in folliculogenesis and ovulation was further
      analyzed. Evaluation of ovarian follicle populations in wild-type and ERbeta
      knockout (betaERKO) ovaries revealed reduced late antral growth and ovulatory
      capacity of betaERKO follicles, indicated by reduced numbers of large antral
      follicles and corpora lutea and increased atresia of large antral follicles. An
      in vitro culture system was used to study growth, rupture, and luteinization of
      wild-type, ERalpha knockout (alphaERKO) and betaERKO ovarian follicles. alphaERKO
      follicles exhibited wild-type-like growth and ovulation rates but an increased
      capacity to synthesize estradiol. In contrast, betaERKO follicles showed a
      significant lack of progression from early antral to large antral stage,
      decreased estradiol production, and reduced ovulation. Expression patterns of
      several genes involved in follicle maturation and ovulation were analyzed in
      follicles grown in vitro. Ar, Pgr, and Has2 mRNA expression levels were the same
      among the three genotypes. However, betaERKO follicles showed reduced expression
      of Cyp19 mRNA during follicle maturation and reduced Lhcgr and Ptgs2 mRNA
      expression after human chorionic gonadotropin stimulus. Luteinization occurs
      normally in alphaERKO and betaERKO follicles, shown by increased progesterone
      secretion and increased cdkn1b mRNA expression after human chorionic
      gonadotropin. Collectively, these data indicate that ERbeta, but not ERalpha,
      plays a direct role in folliculogenesis. ERbeta appears to facilitate follicle
      maturation from the early antral to the preovulatory stage.

PMID- 15731358
TI  - Cloning and characterization of a 5' regulatory region of the prolactin receptor
      associated protein/17{beta} hydroxysteroid dehydrogenase 7 gene.
AB  - Prolactin receptor-associated protein (PRAP) originally cloned in our laboratory
      was shown to be a novel, luteal isoform of 17beta hydroxysteroid dehydrogenase 7
      (17betaHSD7). In this study, we cloned the promoter region of rat PRAP/17betaHSD7
      and investigated the mechanisms regulating both basal activity and LH-induced
      repression of this promoter. Truncated and site-specific mutants of
      PRAP/17betaHSD7 promoter identified two enhancer regions that contained highly
      conserved Sp1 binding site and bound Sp1 from nuclear extracts of both corpora
      lutea and a rat luteal cell line. Repression of PRAP/17betaHSD7 expression and
      promoter activity by human chorionic gonadotropin/forskolin was localized to a 
      52-bp proximal segment of the promoter. This region contained a conserved CCAAT
      site and bound nuclear factor Y; binding of this transcription factor was
      inhibited by human chorionic gonadotropin in vivo. Furthermore, mutation of the
      nuclear factor Y site in the -52-bp promoter-reporter construct abolished
      forskolin-mediated inhibition of the promoter in a rat luteal cell line. In
      summary, we have identified the promoter elements involved in the basal
      expression of PRAP/17betaHSD7. We have also found that LH-mediated repression of
      this gene is at the level of transcription and involves inhibition of nuclear
      factor YA binding to the CCAAT site within the proximal promoter.

PMID- 15731359
TI  - Blockade of rapid versus prolonged extracellularly regulated kinase 1/2
      activation has differential effects on insulin-induced gene expression.
AB  - In the present work, insulin's regulation of expression of activating
      transcription factor 3 (ATF-3), the putative transcription factor proline-rich
      induced protein (Pip)92, and insulin-inducible gene-1 (Insig-1) (an ER resident
      protein involved in regulation of sterol-responsive element-binding protein 1
      activation) have been examined in a liver-derived cell line (rat H4IIE hepatoma
      cells). We report that: 1) insulin-induced transcription of ATF-3, Pip92, and
      Insig-1 required MEK-ERK activation; 2) insulin-induced transcription of ATF-3
      and Pip92 reached maximum levels within 15 min and was blocked by wortmannin but
      not LY294002; 3) in contrast, the maximum level of insulin-induced transcription
      of Insig-1 was delayed and was not blocked by either wortmannin or LY294002; 4)
      insulin activated ERK1/2 in two distinct phases, a rapid peak and a later
      plateau; 5) the delayed plateau phase of insulin-induced ERK1/2 activation was
      partially phosphatidylinositol 3-OH-kinase dependent; and 6) however, the rapid,
      insulin-induced peak of ERK1/2 activation was blocked by wortmannin but not
      LY294002.

PMID- 15731361
TI  - Congenital adrenal hyperplasia: the molecular basis of 21-hydroxylase deficiency
      in H-2(aw18) mice.
AB  - The mouse strain H-2(aw18) shows typical characteristics of 21-hydroxylase
      deficiency (21-OHD). A deletion of the active Cyp21a1 gene has been postulated;
      however, the changes on the nucleotide level are still unknown. To investigate
      whether this animal model, the only one available, is suitable for studying
      congenital adrenal hyperplasia in man, a detailed analysis of the Cyp21 locus has
      been performed to ascertain the genetic cause of 21-OHD in H-2(aw18) mice. We
      demonstrate that 21-OHD is caused by unequal crossing over between the active
      Cyp21a1 gene and the pseudogene resulting in a hybrid Cyp21a1-Cyp21a2-p gene
      including a partial deletion of Cyp21a1. Next to several pseudogene-specific
      point mutations, various novel missense mutations and a nonsense mutation are
      present. Enzyme activity for each point mutation has been determined in vitro and
      the structure-function relationship has been studied by sequence conservation
      analysis and a three-dimensional murine 21-hydroxylase protein (Cyp21) structure
      model. The mutations are classified in three classes: I, no or minor decrease in
      enzyme activity: R238Q, P465L, R361K, A362V, P458L; II, loss of enzyme activity
      caused by inefficient electron flux: R346H, R400C; III, loss of activity due to
      deficient substrate binding: I462F, L464F. The combination of in vitro protein
      expression and three-dimensional structure modeling provides a valuable tool to
      understand the role of the different mutations and polymorphisms on the resulting
      enzyme activity. The underlying genetic mechanisms are also known to be
      responsible for 21-OHD in humans, so rodent 21-OHD turns out to be an excellent
      genetic model for studying the human disease.

PMID- 15731360
TI  - A Graves' disease-associated Kozak sequence single-nucleotide polymorphism
      enhances the efficiency of CD40 gene translation: a case for translational
      pathophysiology.
AB  - We analyzed the mechanism by which a Graves' disease-associated C/T polymorphism
      in the Kozak sequence of CD40 affects CD40 expression. CD40 expression levels on
      B cells in individuals with CT and TT genotypes were decreased by 13.3 and 39.4%,
      respectively, compared with the levels in CC genotypes (P = 0.012). Similarly,
      Rat-2 fibroblasts transfected with T-allele cDNA expressed 32.2% less CD40
      compared with their C-allele-transfected counterparts (P = 0.004). Additionally,
      an in vitro transcription/translation system showed that the T-allele makes 15.5%
      less CD40 than the C-allele (P < 0.001), demonstrating that the effect of the
      single-nucleotide polymorphism (SNP) on CD40 expression is at the level of
      translation. However, the SNP did not affect transcription, because the mRNA
      levels of CD40, as measured by quantitative RT-PCR, were independent of genotype.
      Therefore, our results may suggest that the C allele of the CD40 Kozak SNP, which
      is associated with Graves' disease, could predispose to disease by increasing the
      efficiency of translation of CD40 mRNA.

PMID- 15731362
TI  - Estrogen therapy fails to alter amyloid deposition in the PDAPP model of
      Alzheimer's disease.
AB  - Epidemiological studies implicate estrogen deprivation as a risk factor for
      Alzheimer's disease and postmenopausal estrogen replacement as protective factor.
      One potential mechanism involves estrogen attenuation of beta-amyloid (Abeta)
      peptide accumulation. We examined the effect of estrogen on amyloid accumulation
      in female PDAPP mice, which express human amyloid precursor protein (APP) with
      the V717F mutation. These animals deposit Abeta 1-42 in the hippocampus and
      neocortex and develop Alzheimer-like neuropathology. Mice were subjected to
      ovariectomy, ovariectomy with estrogen replacement, or sham surgery at 3 months
      of age, and levels of cerebral Abeta 1-40 and 1-42 were determined after 5 months
      of treatment. Neither estrogen deprivation nor estrogen replacement altered Abeta
      accumulation in the hippocampus or neocortex. Similarly, immunoreactivity for
      full-length human APP and secreted APPalpha was unchanged. Estrogen status of the
      animals was confirmed using a variety of techniques, including uterine and
      pituitary weight, vaginal cytology, and plasma estradiol concentrations. There
      was no correlation between plasma estradiol levels and accumulation of either
      Abeta 1-40 or Abeta 1-42 in the brain. Our observations indicate that long-term
      estrogen therapy does not alter amyloid pathology in PDAPP mice, an animal model
      of Alzheimer's disease, and question the role of estrogen in Abeta deposition in
      brain.

PMID- 15731363
TI  - Pancreatic islet-specific expression of an insulin-like growth factor-I transgene
      compensates islet cell growth in growth hormone receptor gene-deficient mice.
AB  - Both GH and IGF-I stimulate islet cell growth, inhibit cell apoptosis, and
      regulate insulin biosynthesis and secretion. GH receptor gene deficiency (GHR(-/
      )) caused diminished pancreatic islet cell mass and serum insulin level and
      elevated insulin sensitivity. Because IGF-I gene expression was nearly abolished
      in these mice, we sought to determine whether that had caused the islet defects.
      To restore IGF-I level, we have generated transgenic mice that express rat IGF-I
      cDNA under the direction of rat insulin promoter 1 (RIP-IGF). Using RNase
      protection assay and immunohistochemistry, the IGF-I transgene expression was
      revealed specifically in pancreatic islets of the RIP-IGF mice, which exhibited
      normal growth and development and possess no abnormalities in glucose
      homeostasis, insulin production, and islet cell mass. GHR(-/-) mice exhibited 50%
      reduction in the ratio of islet cell mass to body weight and increased insulin
      sensitivity but impaired glucose tolerance. Compared with GHR(-/-) alone, IGF-I
      overexpression on a GHR(-/-) background caused no change in the diminished blood
      glucose and serum insulin levels, pancreatic insulin contents, and insulin
      tolerance but improved glucose tolerance and insulin secretion. Remarkably, islet
      specific overexpression of IGF-I gene in GHR(-/-) mice restored islet cell mass,
      at least partially through cell hypertrophy. Interestingly, double-transgenic
      male mice demonstrated a transient rescue in growth rates vs. GHR(-/-) alone, at
      2-3 months of age. Our results suggest that IGF-I deficiency is part of the
      underlying mechanism of diminished islet growth in GHR(-/-) mice and are
      consistent with the notion that IGF-I mediates GH-induced islet cell growth.

PMID- 15731364
TI  - Release of transgenic human insulin from gastric g cells: a novel approach for
      the amelioration of diabetes.
AB  - We explored the hypothesis that meal-regulated release of insulin from gastric G
      cells can be used for gene therapy for diabetes. We generated transgenic mice in
      which the coding sequence of human insulin has been knocked into the mouse
      gastrin gene. Insulin was localized specifically to antral G cells of G-InsKi
      mice by double immunofluorescence staining using antibodies against insulin and
      gastrin. Insulin extracted from antral stomach of G-InsKi mice decreased blood
      glucose upon injection into streptozotocin-diabetic mice. Intragastric
      administration of peptone, a known potent luminal stimulant of gastrin secretion,
      induced an increase in circulating levels of transgenic human insulin from 10.7
      +/- 2 to 23.3 +/- 4 pm in G-InsKi mice. Although G cell-produced insulin
      decreased blood glucose in G-InsKi mice, it did not cause toxic hypoglycemia.
      Proton pump inhibitors, pharmacological agents that increase gastrin output,
      caused a further increase in the circulating levels of gastric insulin (41.5 +/-
      2 pm). G cell-produced insulin was released into circulation in response to the
      same meal-associated stimuli that control release of gastrin. The most striking
      aspect of the results presented here is that in the presence of the G-InsKi
      allele, Ins2(Akita/+) mice exhibited a marked prolongation of life span. These
      results imply that G cell-derived transgenic insulin is beneficial in the
      amelioration of diabetes. We suggest that an efficient G cells-based insulin gene
      therapy can relieve diabetic patients from daily insulin injections and protect
      them from complications of insulin insufficiency while avoiding episodes of toxic
      hypoglycemia.

PMID- 15731365
TI  - Homeostatic responses in the adrenal cortex to the absence of aldosterone in
      mice.
AB  - To study the effects of decreased amounts or absence of aldosterone on
      development and endocrine function, we have disrupted the mouse gene, Cyp11b2,
      coding for aldosterone synthase (AS) by replacing its first two exons with
      sequences coding for enhanced green fluorescent protein. The null pups fail to
      thrive postnatally, and about 30% die between d 7 and 28. Aldosterone in plasma
      and AS mRNA in adrenal glands are undetectable in the null mice. Adult AS-null
      mice are small, weigh 75% of wild type, are hypotensive, have increased
      concentrations of plasma K(+) and corticosterone, and a decreased concentration
      of plasma Cl(-). Their plasma renin and angiotensin II concentrations are 45x and
      4x wild type. The adrenal cortex is disorganized and has cells that contain
      marked accumulations of lipid. The zona glomerulosa is widened and includes
      easily detectable renin-containing cells, not seen in the wild-type adrenal
      gland. In the AS-/- adrenals, the level of mRNA for Cyp11b1, coding for 11beta
      hydroxylase, is 150% wild type. The adrenal glands of the null mice consequently
      show evidence of a greatly activated renin-angiotensin system and up-regulation
      of glucocorticoid production. In the AS-null mice enhanced green fluorescent
      protein fluorescence is mainly at the boundary between the cortex and medulla,
      where apoptotic cells are numerous. These data are consistent with the absence of
      aldosterone in the AS-null mice inducing an increased cell-turnover of cells in
      the adrenals that normally become AS expressing and their migration to the
      medullary boundary where they apoptose.

PMID- 15731366
TI  - Conditional expression of a glucocorticoid receptor transgene in thymocytes
      reveals a role for thymic-derived glucocorticoids in thymopoiesis in vivo.
AB  - We and others have previously reported that thymic epithelial cells produce
      glucocorticoids (GCs). In vitro studies have also suggested that thymic-derived
      GCs play a role in the development of thymocytes. However, until now it has not
      yet been established whether thymic-derived GCs play a role in thymopoiesis in
      vivo. To investigate this, we conditionally overexpressed the GC receptor (GR) in
      thymocytes using transgenic mice with a tetracycline-inducible expression system.
      The influence of systemic GCs was excluded by adrenalectomizing the transgenic
      mice before the GR induction. Conditional expression of transgenic GR in the
      thymocytes of adrenalectomized transgenic mice led to a decrease in the thymocyte
      number. This was associated with increased thymocyte apoptosis. The effect of
      thymic-derived GCs on the thymocytes was confirmed after transgenic GR induction
      in a thymic organ culture system. Finally, the GR antagonist RU486 increased
      thymocyte number in adrenalectomized mice in vivo and prevented a reduction in
      thymocyte number in thymic organ culture after transgenic GR induction. These
      observations further confirmed a role for the thymic-derived GCs in regulating
      thymocyte homeostasis in vivo.

PMID- 15731367
TI  - Fungal liver infection in immunocompromised patients: depiction with multiphasic
      contrast-enhanced helical CT.
AB  - PURPOSE: To retrospectively assess multiphasic (nonenhanced, arterial phase, and
      portal venous phase) computed tomography (CT) of the liver for depiction of
      hepatic fungal infection in immunocompromised patients. MATERIALS AND METHODS:
      The institutional ethics review board approved the study and waived the
      requirement for informed consent. Sixty multiphasic hepatic CT examinations were
      performed in 39 immunocompromised patients who fulfilled the criteria for having
      probable or proved fungal liver infection. The detection and conspicuity of focal
      liver lesions were assessed on scans obtained during each CT phase. The lesion
      enhancement pattern was determined, and, accordingly, lesions were stratified
      into two groups: lesions suggestive of infection (with ring enhancement patterns
      or high attenuation) and nonspecific hypoattenuating lesions. Statistical
      analyses were performed by using logistic regression with generalized estimating
      equations. RESULTS: A total of 536 liver lesions detected at 36 CT examinations
      with results positive for fungal infection were assessed. All 36 (100%)
      examinations yielded positive results during the arterial phase, whereas 25 (69%)
      of them yielded positive results during the portal venous phase (P < .001). At
      lesion-by-lesion analysis, the arterial phase scans depicted significantly more
      lesions (483 of 536 [90%]) than the portal venous phase (329 of 536 [61%]) and
      nonenhanced (265 of 465 [57%]) scans (P < .001 for both comparisons). In
      addition, on arterial phase scans, 386 of 483 lesions, as compared with 134 of
      329 lesions on portal venous phase scans (P < .001), were judged to have an
      enhancement pattern suggestive of infection. The CT phases did not differ
      significantly in terms of the conspicuity of detected lesions. CONCLUSION: In
      patients suspected of having hepatic fungal infection, arterial phase CT depicts
      significantly more hepatic lesions than does CT performed during the other
      phases, and it reveals more lesions with enhancement patterns suggestive of
      infection. Arterial phase CT should be performed in addition to portal venous
      phase CT in patients suspected of having hepatic fungal infection.

PMID- 15731368
TI  - Dysmenorrhea: evaluation with cine-mode-display MR imaging--initial experience.
AB  - PURPOSE: To prospectively evaluate uterine contractility during menstruation and
      its relation to primary dysmenorrhea by using magnetic resonance (MR) imaging
      with cine mode display. MATERIALS AND METHODS: The university ethics committee
      approved the study protocol, and all subjects gave written informed consent.
      Nineteen healthy women were examined during menstrual cycle days 1-3 by using a
      1.5-T-magnet unit. Sixty serial half-Fourier rapid acquisition with relaxation
      enhancement MR images of the uterus were obtained every 3 seconds for 3 minutes
      and displayed in cine mode. MR images were analyzed in terms of thickness of the
      inner low-signal-intensity myometrial layer, presence of endometrial distortion,
      and uterine peristalsis detectability. Pain was assessed by using a four-point
      scale. For 56 MR imaging cases, the association between MR imaging findings and
      pain degree was examined with Spearman correlation and Mann-Whitney tests. MR
      imaging findings in the dysmenorrheic and eumenorrheic subject groups were
      compared by using Mann-Whitney and chi(2) tests. The area of the uterine
      myometrium in both groups was calculated for quantitative assessment of uterine
      contraction and was compared between the groups by using the Student t test.
      RESULTS: MR imaging findings revealed marked changes during cycle days 1-3.
      Thickness of the inner low-signal-intensity myometrial layer and endometrial
      distortion were significantly associated with pain degree (P < .001), while
      uterine peristalsis was undetectable when pain was severe or moderate. The area
      of the uterine myometrium significantly decreased during cycle days 1-3 in the
      dysmenorrheic group, as compared with that in the eumenorrheic group (P = .010).
      CONCLUSION: MR imaging features of the uterus on cycle days 1-3 correlated with
      pain degree. Cine-mode-display MR imaging is a potential tool for evaluating
      dysmenorrhea.

PMID- 15731369
TI  - Prognostic factors for survival in patients with hepatocellular carcinoma after
      percutaneous microwave ablation.
AB  - PURPOSE: To determine the long-term survival and prognostic factors in patients
      with hepatocellular carcinoma treated with percutaneous microwave ablation.
      MATERIALS AND METHODS: Institutional review board approval and informed consent
      were obtained. A database of cases of hepatocellular carcinoma in 288 patients
      (259 men, 29 women; mean age, 54.8 years +/- 11.4 [standard deviation]; age
      range, 25-82 years) with 477 histologically proved lesions who underwent
      percutaneous microwave coagulation therapy between May 1994 and October 2002 was
      retrospectively analyzed. Prognostic factors for survival were evaluated by means
      of univariate and multivariate analyses. RESULTS: The mean follow-up period after
      microwave ablation was 31.41 months +/- 20.43 (range, 5-106 months). The 1-, 2-,
      3-, 4-, and 5-year cumulative survival rates among all 288 patients were 93%,
      82%, 72%, 63%, and 51%, respectively. Ninety-three patients (32%) died. Local
      recurrence or new tumors occurred in 100 patients (35%). Age (P = .836), sex (P =
      .073), preablation serum alpha-fetoprotein level (P = .136), and preablation
      treatment (P = .256) were not related to prognosis, while tumor number (P =
      .004), tumor size (P < .001), Child-Pugh classification (P = .003), tumor
      differentiation (P = .026), and local recurrence or presence of new tumors (P =
      .004) significantly affected survival at univariate analysis. At multivariate
      analysis, only tumor size (P < .001), number of nodules (P = .005), and Child
      Pugh classification (P = .01) each had a significant effect on survival.
      CONCLUSION: With use of microwave ablation, there is a high probability of long
      term survival of patients with a single lesion of 4.0 cm or less in maximum
      diameter and Child-Pugh class A cirrhosis.

PMID- 15731370
TI  - Contrast-enhanced MR angiography of peripheral arteries including pedal vessels
      at 1.0 T: feasibility study with dedicated peripheral angiography coil.
AB  - PURPOSE: To prospectively determine feasibility of contrast material-enhanced
      magnetic resonance (MR) angiography of the peripheral arteries from distal aorta
      to pedal arteries with a 1.0-T system and a dedicated phased-array coil.
      MATERIALS AND METHODS: Twenty-seven patients with peripheral arteriosclerotic
      occlusive disease underwent contrast-enhanced MR angiography with an automatic
      moving-table technique. In addition, lower-leg and pedal arteries were examined
      without table movement (hybrid technique). Two radiologists independently
      reviewed MR angiograms to assess image quality and grade stenosis in 13 segments
      per leg. Each was blinded to patients' clinical data. Twenty-five of the patients
      also underwent conventional angiography. Stenosis grade at conventional
      angiography was assessed by two radiologists in consensus. Interobserver
      variability for stenosis grade at MR angiography was calculated with Cohen kappa
      test. Specificity and sensitivity of MR angiography in detection of stenosis of
      more than 50% and occlusion were calculated for both observers. The study was
      approved by the local ethics committee. RESULTS: In 14 of the 27 patients, hybrid
      technique was superior to moving-table technique because there was less venous
      overlap (11 patients), fewer motion artifacts (one patient), or both (two
      patients). In nine patients, there was no difference between techniques; in four
      patients, moving-table technique was superior. Stenosis grade was analyzed in 698
      segments with MR angiography and in 638 segments with both conventional and MR
      angiography. Kappa analysis of interobserver agreement with MR angiography
      yielded a score of 0.84. For the 638 segments evaluated with both conventional
      and MR angiography, observers 1 and 2 assigned same grade of stenosis with both
      modalities in 558 and 555 segments, respectively. Sensitivity for stenoses
      greater than 50% and occlusion was 94.4% and 91.1% for observers 1 and 2,
      respectively, and specificity was 90.6% and 91.3%. More distal runoff vessels
      were shown with MR angiography in seven cases and with conventional angiography
      in two cases. CONCLUSION: Contrast-enhanced MR angiography of the peripheral
      vessels with a 1.0-T system and dedicated peripheral angiography coil is
      feasible, and in some cases, it provides additional information compared with
      conventional angiography.

PMID- 15731371
TI  - Pulmonary vein diameter, cross-sectional area, and shape: CT analysis.
AB  - PURPOSE: To retrospectively establish normal values for pulmonary vein diameter,
      cross-sectional area, and shape depicted at computed tomography (CT). MATERIALS
      AND METHODS: Institutional review board waived patient consent requirement and
      approved the study. Thin-section contrast material-enhanced spiral chest CT scans
      in 104 patients, 68 women and 36 men (age range, 19-86 years; mean, 49 years)
      referred to exclude pulmonary embolism, were retrospectively reviewed. Short-axis
      diameter and cross-sectional area of the four major pulmonary veins (right
      inferior and superior, left inferior and superior) were measured at a workstation
      by using oblique reconstructions. Each vein was measured at six locations, 5 mm
      apart, starting at atrial ostium. Each measurement was performed three times by
      an experienced thoracic radiologist, and the mean value was recorded. Roundness
      was estimated by comparing the ratio of the calculated cross-sectional area to
      that measured. Mixed effects model was used to compare men and women relative to
      the distribution of diameters and surface areas and to compare roundness of the
      right and left veins. RESULTS: Mean pulmonary vein diameters at the ostia were
      variable: right superior, 11.4-12.4 mm; left superior, 9.6-10.5 mm; right
      inferior, 12.3-13.1 mm; and left inferior, 9.0-9.9 mm. Diameter and cross
      sectional area of the left superior pulmonary vein were significantly larger in
      men than in women (P < .005). As expected, the caliber of three of the four veins
      gradually increased as they approached the left atrium. Caliber of the left
      inferior pulmonary vein decreased as it entered the left atrium. None of the
      veins were round; all were ovoid. Left-sided veins and venous ostia were less
      round than right-sided veins (P < .001). CONCLUSION: Pulmonary vein diameter,
      cross-sectional area, and shape vary. Particular care must be taken when the left
      inferior pulmonary vein is evaluated for stenosis, as it normally narrows as it
      enters the left atrium.

PMID- 15731372
TI  - Secondary cleft sign as a marker of injury in athletes with groin pain: MR image
      appearance and interpretation.
AB  - PURPOSE: To determine whether the secondary cleft sign demonstrated in the
      symphysis pubis at magnetic resonance (MR) imaging is a marker of injury in
      athletes presenting with groin pain. MATERIALS AND METHODS: Ethics review board
      approval was not required for studies involving retrospective image or case
      record review; informed consent for review was not required. Eighteen male
      athletes (mean age, 24 years; age range, 19-32 years) were included for study.
      All patients underwent radiography and MR imaging (coronal fast spin-echo T1
      weighted, transverse fast spin-echo T2-weighted, and coronal turbo short
      inversion time inversion-recovery [STIR] imaging) of the pelvis. Subsequent image
      guided nonionic contrast material injection was followed by a 0.5% bupivacaine
      hydrochloride (1 mL) and methyprednisolone acetate (20 mg) injection into the
      central cleft of the symphysis pubis. Comparison was made between imaging
      findings at symphyseal cleft injection and appearances at preprocedure MR
      imaging, with specific reference to the presence of a secondary cleft. The
      sensitivity and specificity of MR imaging in demonstrating the secondary cleft
      sign were compared with those of the reference standard, imaging at symphyseal
      cleft injection. MR images from a reference group of 70 asymptomatic athletes who
      underwent STIR imaging of the pelvis were analyzed for evidence of a secondary
      cleft. RESULTS: Osteitis pubis was diagnosed in six patients on the basis of
      radiography and/or MR imaging. A secondary cleft was identified in 12 of 18
      patients at MR imaging, was best visualized at coronal STIR imaging, and was
      confirmed in each patient during contrast material injection into the central
      physiologic symphyseal cleft. In no patient was a secondary cleft identified at
      symphyseal cleft injection and not identified at MR imaging (sensitivity and
      specificity, 100%). In each patient, the side of the secondary cleft corresponded
      to the side of symptoms that responded to local anesthetic and steroid injection.
      Four of the six patients with osteitis pubis had evidence of a secondary cleft.
      In one patient, a secondary cleft was not identified at MR imaging or symphyseal
      cleft injection, but adductor avulsion was identified at MR imaging. No evidence
      of a secondary cleft sign at MR imaging was identified in the reference group.
      CONCLUSION: The secondary cleft sign demonstrated at MR imaging is a marker of
      groin injury in athletes presenting with groin pain.

PMID- 15731373
TI  - Cerebral infarction: incidence and risk factors after diagnostic and
      interventional cardiac catheterization--prospective evaluation at diffusion
      weighted MR imaging.
AB  - PURPOSE: To prospectively evaluate incidence of clinically silent and clinically
      apparent embolic cerebral infarction following diagnostic and interventional
      coronary angiography and associated risk factors. MATERIALS AND METHODS: Written
      informed consent was obtained from all patients, and the study was approved by
      the research ethics committee of University of Heidelberg, Germany. Fifty-two
      patients, including 37 men (mean age, 66.1 years +/- 11.9 [standard deviation])
      and 15 women (mean age, 65.3 years +/- 10.3), undergoing elective cardiac
      catheterization were examined 3-26 hours (mean, 15.3 hours +/- 6) before and 12
      48 hours (mean, 25.9 hours +/- 10.4) after cardiac catheterization. Magnetic
      resonance imaging protocol included isotropic and anisotropic diffusion-weighted
      single-shot echo-planar sequences. T2-weighted turbo spin-echo and T1-weighted
      spin-echo sequences also were performed. Apparent diffusion coefficient maps were
      calculated to exclude false-positive reading results on diffusion-weighted images
      because of T2 shine-through effect. Images were assessed by two experienced
      radiologists blinded to clinical data. Cardiac catheterization was performed by
      11 experienced cardiologists to exclude operator-related risk. A neurologic
      examination according to the National Institutes of Health Stroke Scale and
      Barthel index was performed by a senior cardiologist before acquisition of each
      image. Sixteen clinical and angiographic variables were analyzed with univariate
      analysis for ability to predict occurrence of cerebral infarction. RESULTS: No
      embolic cerebral lesions could be detected at diffusion-weighted imaging before
      catheterization. After coronary angiography, seven (15%) of 48 patients
      demonstrated nine focal cerebral infarcts affecting anterior and posterior
      circulation. Patients remained asymptomatic. Of all tested variables, only
      duration of the procedure was identified as an independent predictor of
      occurrence of cerebral infarction (P < .05). CONCLUSION: In this prospective
      study, asymptomatic cerebral infarction following cardiac catheterization
      occurred in 15% of patients in whom duration of the procedure was significantly
      longer than in those without infarction (P = .017).

PMID- 15731374
TI  - Assessment of regional left ventricular function: accuracy and reproducibility of
      positioning standard short-axis sections in cardiac MR imaging.
AB  - The assessment of regional left ventricular (LV) function with cardiac magnetic
      resonance (MR) cine techniques requires a standardized section positioning. A
      simple selective short-axis method for selective positioning of three short-axis
      sections (basal, midcavity, apical) was tested for its accuracy, compared with
      accepted criteria, in 21 volunteers (mean age, 32 years +/- 11) and in 23
      patients with myocardial infarction (mean age, 56 years +/- 12). Reproducibility
      of section positioning and of regional LV parameters was tested in the
      volunteers. Among the six accuracy criteria defined for standard sections, the
      selective short-axis approach had an average accuracy of 90.9% in volunteers and
      87.7% in patients, compared with 92.1% and 90.6%, respectively, for a
      multisection approach covering the whole LV. There was very good reproducibility
      of the selected intersection gap (r = 0.89, P < .001) and of measured midcavity
      end-diastolic diameters in vertical (r = 0.83, P < .001) and horizontal (r =
      0.85, P < .001) long-axis orientations. The proposed method produces standardized
      short-axis section positions that meet the recommendations for cardiac imaging.
      The study was approved by the local ethics committee, and all subjects gave
      written informed consent.

PMID- 15731375
TI  - Reduced tumor growth with combined radiofrequency ablation and radiation therapy
      in a rat breast tumor model.
AB  - PURPOSE: To determine whether use of combined radiofrequency (RF) ablation and
      external-beam radiation therapy increases end-point survival beyond that with
      either RF ablation or radiation therapy alone in an animal tumor model. MATERIALS
      AND METHODS: With a protocol approved by the institutional animal care and use
      committee, R3230 mammary adenocarcinoma (12.5 mm +/- 0.6 [standard deviation])
      was implanted subcutaneously into 107 female Fischer 344 rats. Initially, 42
      tumors were randomized into four treatment groups: (a) RF ablation (70 degrees C
      for 5 minutes) alone, (b) RF ablation followed by radiation therapy with a total
      dose of 20 Gy, (c) 20-Gy radiation alone, and (d) no treatment. Another 19 tumors
      were randomized to receive (e) RF ablation (70 degrees C for 5 minutes) followed
      by 5-Gy radiation, (f) 5-Gy radiation alone, or (g) no treatment. Animals were
      followed up until survival end point (either until tumor growth to 30 mm in
      diameter, or for 120 days if no tumor was seen in mammary fat pad or chest wall).
      Results were analyzed with the Kaplan-Meier method. Histopathologic analysis was
      performed in 15 additional tumors at survival end point and 18 other
      representative tumors at other specified end points. RESULTS: Combined RF
      ablation and 20-Gy radiation resulted in complete local control in nine (82%) of
      11 tumors, compared with one (9%) of 11 tumors treated with RF ablation alone and
      one (17%) of six treated with RF ablation and 5-Gy radiation (P < .001). No local
      control was achieved in rats with radiation therapy alone or in controls. Median
      end-point survival was 12 days for controls, 20 days with RF ablation or 5-Gy
      radiation alone, 30 days with RF ablation plus 5-Gy radiation, 40 days with 20-Gy
      radiation alone, and 120 days with RF ablation plus 20-Gy radiation. Mean end
      point survival was 13 days +/- 5 (standard deviation) for the control group, 34
      days +/- 31 with RF ablation alone, and 43 days +/- 16 with 20-Gy radiation
      alone. Mean survival was significantly greater with 20-Gy radiation and RF
      ablation combined: 94 days +/- 34 (P < .001 compared with all other groups). Mean
      survival for rats that received 5-Gy radiation with RF ablation versus without
      was 46 days +/- 37 versus 24 days +/- 11, respectively. CONCLUSION: Combined RF
      ablation and external-beam radiation therapy increased animal survival compared
      with that with either of the treatments alone or with no treatment.

PMID- 15731376
TI  - Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of
      dendritic contrast agents in tumor angiogenesis in mice.
AB  - PURPOSE: To evaluate the relationship between dynamic contrast agent-enhanced
      magnetic resonance (MR) imaging-derived kinetic parameters and contrast agents of
      equal chemical composition and configuration but with different molecular weights
      in a tumor angiogenesis model. MATERIALS AND METHODS: This study was approved by
      the ethical review committee. Maintenance and care of animals was in compliance
      with guidelines set by the institutional animal care committee. Dynamic contrast
      enhanced MR imaging was performed with dendritic contrast agents in 16 mice with
      tumor xenografts; mice were placed in groups of four for each molecular weight of
      the contrast agent. The magnitude and spatial distribution of kinetic parameters
      (transfer coefficient [K(PS)] and plasma fraction [f(PV)]) were compared with
      molecular weight of the contrast agent by determining the Spearman correlation
      coefficient (r) and the quantitative relationship between the endothelial K(PS)
      and molecular weight. RESULTS: Inverse relationships between molecular weight of
      contrast agent and K(PS) and f(PV) of tumor rim (r = -0.8, P < .001 and r = -0.5,
      P = .04, respectively) and core (r = -0.7, P = .004 and r = -0.6, P = .01,
      respectively) were observed. The quantitative relationship between K(PS) and
      molecular weight (MW) was K(PS) = 0.4/MW(0.44). A decreasing stepwise pattern in
      f(PV) was noted between contrast agents with low (0.7- and 3.0-kDa) molecular
      weight and those with high (12- and 51-kDa) molecular weight. CONCLUSION:
      Macromolecular permeability is best measured with high-molecular-weight contrast
      agents; endothelial K(PS) values measured with low-molecular-weight contrast
      agents incorporate tissue perfusion and permeability and demonstrate
      heterogeneous microcirculatory flow.

PMID- 15731378
TI  - The first crystal structure of a macromolecular assembly under high pressure:
      CpMV at 330 MPa.
AB  - The structure of cubic Cowpea mosaic virus crystals, compressed at 330 MPa in a
      diamond anvil cell, was refined at 2.8 A from data collected using ultrashort
      wavelength (0.331 A) synchrotron radiation. With respect to the structure at
      atmospheric pressure, order is increased with lower Debye Waller factors and a
      larger number of ordered water molecules. Hydrogen-bond lengths are on average
      shorter and the cavity volume is strongly reduced. A tentative mechanistic
      explanation is given for the coexistence of disordered and ordered cubic crystals
      in crystallization drops and for the disorder-order transition observed in
      disordered crystals submitted to high pressure. Based on such explanation, it can
      be concluded that pressure would in general improve, albeit to a variable extent,
      the order in macromolecular crystals.

PMID- 15731379
TI  - Large-scale conformational dynamics of the HIV-1 integrase core domain and its
      catalytic loop mutants.
AB  - HIV-1 integrase is one of the three essential enzymes required for viral
      replication and has great potential as a novel target for anti-HIV drugs.
      Although tremendous efforts have been devoted to understanding this protein, the
      conformation of the catalytic core domain around the active site, particularly
      the catalytic loop overhanging the active site, is still not well characterized
      by experimental methods due to its high degree of flexibility. Recent studies
      have suggested that this conformational dynamics is directly correlated with
      enzymatic activity, but the details of this dynamics is not known. In this study,
      we conducted a series of extended-time molecular dynamics simulations and locally
      enhanced sampling simulations of the wild-type and three loop hinge mutants to
      investigate the conformational dynamics of the core domain. A combined total of
      >480 ns of simulation data was collected which allowed us to study the
      conformational changes that were not possible to observe in the previously
      reported short-time molecular dynamics simulations. Among the main findings are a
      major conformational change (>20 A) in the catalytic loop, which revealed a
      gatinglike dynamics, and a transient intraloop structure, which provided a
      rationale for the mutational effects of several residues on the loop including
      Q(148), P(145), and Y(143). Further, clustering analyses have identified seven
      major conformational states of the wild-type catalytic loop. Their implications
      for catalytic function and ligand interaction are discussed. The findings
      reported here provide a detailed view of the active site conformational dynamics
      and should be useful for structure-based inhibitor design for integrase.

PMID- 15731380
TI  - Estimation of anisotropic optical parameters of tissue in a slab geometry.
AB  - The scattering and absorption coefficients of many homogeneous biological tissues
      such as muscle, skin, white matter in the brain, and dentin are often
      anisotropically oriented with respect to their bounding interface. In consequence
      the curves of equal intensity of re-emitted light on the surface of the slab will
      no longer be circular. We here consider the problem of determining the parameters
      allowing one to estimate the angles defining anisotropy, directional bias of
      diffusive spreading, and scattering and absorbing coefficients from data obtained
      from time-gated measurements of light intensity transmitted through a slab of the
      tissue. Our model can be solved exactly and leads to accurate approximations in
      which measured values of the surface intensity are shown to be elliptical. The
      parameters of the ellipses suffice to estimate the anisotropy of the tissue
      interior. A summary of the parameter estimates with the observables from which
      they are found is given in a table. Our analysis is based on a diffusion model.

PMID- 15731381
TI  - Kinetic constraints for formation of steady states in biochemical networks.
AB  - The constraint-based analysis has emerged as a useful tool for analysis of
      biochemical networks. This work introduces the concept of kinetic constraints. It
      is shown that maximal reaction rates are appropriate constraints only for
      isolated enzymatic reactions. For biochemical networks, it is revealed that
      constraints for formation of a steady state require specific relationships
      between maximal reaction rates of all enzymes. The constraints for a branched
      network are significantly different from those for a cyclic network. Moreover,
      the constraints do not require Michaelis-Menten constants for most enzymes, and
      they only require the constants for the enzymes at the branching or cyclic point.
      Reversibility of reactions at system boundary or branching point may
      significantly impact on kinetic constraints. When enzymes are regulated,
      regulations may impose severe kinetic constraints for the formation of steady
      states. As the complexity of a network increases, kinetic constraints become more
      severe. In addition, it is demonstrated that kinetic constraints for networks
      with co-regulation can be analyzed using the approach. In general, co-regulation
      enhances the constraints and therefore larger fluctuations in fluxes can be
      accommodated in the networks with co-regulation. As a first example of the
      application, we derive the kinetic constraints for an actual network that
      describes sucrose accumulation in the sugar cane culm, and confirm their validity
      using numerical simulations.

PMID- 15731383
TI  - A directed essential dynamics simulation of peptide folding.
AB  - We present a directed essential dynamics (DED) method for peptide and protein
      folding. DED is a molecular dynamics method based on the essential dynamics
      sampling and the principal component analysis. The main idea of DED is to use
      principal component analysis to determine the direction of the most active
      collective motion of peptides at short intervals of time (20 fs) during the
      folding process and then add an additional force along it to adjust the folding
      direction. This method can make the peptides avoid being trapped in the local
      minima for a long time and enhance the sampling efficiency in conformational
      space during the simulation. An S-peptide with 15 amino acids is used to
      demonstrate the DED method. The results show that DED can lead the S-peptide to
      fold quickly into the native state, whereas traditional molecular dynamics needs
      more time to do this.

PMID- 15731382
TI  - Use of helper enzymes for ADP removal in infrared spectroscopic experiments:
      application to Ca2+-ATPase.
AB  - Adenylate kinase (AdK) and apyrase were employed as helper enzymes to remove ADP
      in infrared spectroscopic experiments that study the sarcoplasmic reticulum
      Ca(2+)-ATPase. The infrared absorbance changes of their enzymatic reactions were
      characterized and used to monitor enzyme activity. AdK transforms ADP to ATP and
      AMP, whereas apyrase consumes ATP and ADP to generate AMP and inorganic
      phosphate. The benefits of using them as helper enzymes are severalfold: i), both
      remove ADP generated after ATP hydrolysis by ATPase, which enables repeat of ATP
      release experiments several times with the same sample without interference by
      ADP; ii), AdK helps maintain the presence of ATP for a longer time by
      regenerating 50% of the initial ATP; iii), apyrase generates free P(i), which can
      help stabilize the ADP-insensitive phosphoenzyme (E2P); and iv), apyrase can be
      used to monitor ADP dissociation from transient enzyme intermediates with
      relatively high affinity to ADP, as shown here for ADP dissociation from the ADP
      sensitive phosphoenzyme intermediate (Ca(2)E1P). The respective infrared spectra
      indicate that ADP dissociation relaxes the closed conformation immediately after
      phosphorylation partially back toward the open conformation of Ca(2)E1 but does
      not trigger the transition to E2P. The helper enzyme approach can be extended to
      study other nucleotide-dependent proteins.

PMID- 15731384
TI  - Protein adsorption orientation in the light of fluorescent probes: mapping of the
      interaction between site-directly labeled human carbonic anhydrase II and silica
      nanoparticles.
AB  - Little is known about the direction and specificity of protein adsorption to
      solid surfaces, a knowledge that is of great importance in many biotechnological
      applications. To resolve the direction in which a protein with known structure
      and surface potentials binds to negatively charged silica nanoparticles,
      fluorescent probes were attached to different areas on the surface of the protein
      human carbonic anhydrase II. By this approach it was clearly demonstrated that
      the adsorption of the native protein is specific to limited regions at the
      surface of the N-terminal domain of the protein. Furthermore, the adsorption
      direction is strongly pH-dependent. At pH 6.3, a histidine-rich area around
      position 10 is the dominating adsorption region. At higher pH values, when the
      histidines in this area are deprotonated, the protein is also adsorbed by a
      region close to position 37, which contains several lysines and arginines.
      Clearly the adsorption is directed by positively charged areas on the protein
      surface toward the negatively charged silica surface at conditions when specific
      binding occurs.

PMID- 15731385
TI  - Energy landscape distortions and the mechanical unfolding of proteins.
AB  - Molecular simulations and an energy landscape analysis are used to examine the
      stretching of a model protein. A mapping of the energy landscape shows that
      stretching the protein causes energy minima and energy barriers to flatten out
      and disappear, and new energy minima to be created. The implications of these
      landscape distortions depend on the timescale regime under which the protein is
      stretched. When the timescale for thermally activated processes is longer than
      the timescale of stretching, the disappearances of energy barriers provide the
      mechanism for protein unfolding. When the timescale for thermally activated
      processes is shorter than the timescale of stretching, the landscape distortions
      influence the stretching process by changing the number and types of energy
      minima in which the system can exist.

PMID- 15731386
TI  - Unfolding and refolding of bovine serum albumin induced by cetylpyridinium
      bromide.
AB  - The interaction of bovine serum albumin (BSA) with cationic surfactant
      cetylpyridinium bromide (CPB) in aqueous solution (pH 7.00) was studied
      quantitatively with ultraviolet (UV)-visible, far-UV, and near-UV circular
      dichroism, fluorescence, small angle x-ray scattering, and nuclear magnetic
      resonance measurement. It was found that CPB at low and high concentrations could
      induce the unfolding and refolding of BSA, respectively. We suggest that in the
      unfolding process, there existed BSA-CPB complex with the "necklace and bead"
      structure in which the unfolded BSA wrapped around CPB micelles, and that the
      hydrophobic interaction between the complexes led to the formation of large
      aggregates. The aromatic headgroup of CPB interacted with the tryptophan residues
      of BSA, resulting in the aromatic ring stacking between BSA and CPB. During the
      refolding process, the BSA molecule was penetrated into the rod micelle of CPB
      and the hydrophobic moiety of the BSA molecule was exposed outside while its
      hydrophilic part was hidden inside, thereby disrupting the aromatic ring
      stacking.

PMID- 15731387
TI  - Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+
      and phosphorylation.
AB  - Calsequestrin, the major calcium sequestering protein in the sarcoplasmic
      reticulum of muscle, forms a quaternary complex with the ryanodine receptor
      calcium release channel and the intrinsic membrane proteins triadin and junctin.
      We have investigated the possibility that calsequestrin is a luminal calcium
      concentration sensor for the ryanodine receptor. We measured the luminal calcium
      concentration at which calsequestrin dissociates from the ryanodine receptor and
      the effect of calsequestrin on the response of the ryanodine receptor to changes
      in luminal calcium. We provide electrophysiological and biochemical evidence
      that: 1), luminal calcium concentration of >/=4 mM dissociates calsequestrin from
      junctional face membrane, whereas in the range of 1-3 mM calsequestrin remains
      attached; 2), the association with calsequestrin inhibits ryanodine receptor
      activity, but amplifies its response to changes in luminal calcium concentration;
      and 3), under physiological calcium conditions (1 mM), phosphorylation of
      calsequestrin does not alter its ability to inhibit native ryanodine receptor
      activity when the anchoring proteins triadin and junctin are present. These data
      suggest that the quaternary complex is intact in vivo, and provides further
      evidence that calsequestrin is involved in the sarcoplasmic reticulum calcium
      signaling pathway and has a role as a luminal calcium sensor for the ryanodine
      receptor.

PMID- 15731388
TI  - Water molecules and hydrogen-bonded networks in bacteriorhodopsin--molecular
      dynamics simulations of the ground state and the M-intermediate.
AB  - Protein crystallography provides the structure of a protein, averaged over all
      elementary cells during data collection time. Thus, it has only a limited access
      to diffusive processes. This article demonstrates how molecular dynamics
      simulations can elucidate structure-function relationships in bacteriorhodopsin
      (bR) involving water molecules. The spatial distribution of water molecules and
      their corresponding hydrogen-bonded networks inside bR in its ground state (G)
      and late M intermediate conformations were investigated by molecular dynamics
      simulations. The simulations reveal a much higher average number of internal
      water molecules per monomer (28 in the G and 36 in the M) than observed in
      crystal structures (18 and 22, respectively). We found nine water molecules
      trapped and 19 diffusive inside the G-monomer, and 13 trapped and 23 diffusive
      inside the M-monomer. The exchange of a set of diffusive internal water molecules
      follows an exponential decay with a 1/e time in the order of 340 ps for the G
      state and 460 ps for the M state. The average residence time of a diffusive water
      molecule inside the protein is approximately 95 ps for the G state and 110 ps for
      the M state. We have used the Grotthuss model to describe the possible proton
      transport through the hydrogen-bonded networks inside the protein, which is built
      up in the picosecond-to-nanosecond time domains. Comparing the water distribution
      and hydrogen-bonded networks of the two different states, we suggest possible
      pathways for proton hopping and water movement inside bR.

PMID- 15731389
TI  - Orientational dynamics and dye-DNA interactions in a dye-labeled DNA aptamer.
AB  - We report the picosecond and nanosecond timescale rotational dynamics of a dye
      labeled DNA oligonucleotide or "aptamer" designed to bind specifically to
      immunoglobulin E. Rotational dynamics in combination with fluorescence lifetime
      measurements provide information about dye-DNA interactions. Comparison of Texas
      Red (TR), fluorescein, and tetramethylrhodamine (TAMRA)-labeled aptamers reveals
      surprising differences with significant implications for biophysical studies
      employing such conjugates. Time-resolved anisotropy studies demonstrate that the
      TR- and TAMRA-aptamer anisotropy decays are dominated by the overall rotation of
      the aptamer, whereas the fluorescein-aptamer anisotropy decay displays a
      subnanosecond rotational correlation time much shorter than that expected for the
      overall rotation of the aptamer. Docking and molecular dynamics simulations
      suggest that the low mobility of TR is a result of binding in the groove of the
      DNA helix. Additionally, associated anisotropy analysis of the TAMRA-aptamer
      reveals both quenched and unquenched states that experience significant coupling
      to the DNA motion. Therefore, quenching of TAMRA by guanosine must depend on the
      configuration of the dye bound to the DNA. The strong coupling of TR to the
      rotational dynamics of the DNA aptamer, together with the absence of quenching of
      its fluorescence by DNA, makes it a good probe of DNA orientational dynamics. The
      understanding of the nature of dye-DNA interactions provides the basis for the
      development of bioconjugates optimized for specific biophysical measurements and
      is important for the sensitivity of anisotropy-based DNA-protein interaction
      studies employing such conjugates.

PMID- 15731390
TI  - Induced fit and the entropy of structural adaptation in the complexation of CAP
      and lambda-repressor with cognate DNA sequences.
AB  - Molecular dynamics (MD) simulations of 5 ns on protein-DNA complexes of
      catabolite-activator protein (CAP), lambda-repressor, and their corresponding
      uncomplexed protein and DNA, are reported. These cases represent two extremes of
      DNA bending, with CAP DNA bent severely and the lambda-operator nearly straight
      when complexed with protein. The calculations were performed using the AMBER
      suite of programs and the parm94 force field, validated for these studies by good
      agreement with experimental nuclear magnetic resonance data on DNA. An explicit
      computational model of structural adaptation and computation of the quasiharmonic
      entropy of association were obtained from the MD. The results indicate that, with
      respect to canonical B-form DNA, the extreme bending of the DNA in the complex
      with CAP is approximately 60% protein-induced and 40% intrinsic to the sequence
      dependent structure of the free oligomer. The DNA in the complex is an
      energetically strained form, and the MD results are consistent with a
      conformational-capture mechanism. The calculated quasiharmonic entropy change
      accounts for the entropy difference between the two cases. The calculated entropy
      was decomposed into contributions from protein adaptation, DNA adaptation, and
      protein-DNA structural correlations. The origin of the entropy difference between
      CAP and lambda-repressor complexation arises more from the additional protein
      adaptation in the case of lambda, than to DNA bending and entropy contribution
      from DNA bending. The entropy arising from protein DNA cross-correlations, a
      contribution not previously discussed, is surprisingly large.

PMID- 15731391
TI  - Following the formation of supported lipid bilayers on mica: a study combining
      AFM, QCM-D, and ellipsometry.
AB  - Supported lipid bilayers (SLBs) are popular models of cell membranes with
      potential biotechnological applications and an understanding of the mechanisms of
      SLB formation is now emerging. Here we characterize, by combining atomic force
      microscopy, quartz crystal microbalance with dissipation monitoring, and
      ellipsometry, the formation of SLBs on mica from sonicated unilamellar vesicles
      using mixtures of zwitterionic, negatively and positively charged lipids. The
      results are compared with those we reported previously on silica. As on silica,
      electrostatic interactions were found to determine the pathway of lipid
      deposition. However, fundamental differences in the stability of surface-bound
      vesicles and the mobility of SLB patches were observed, and point out the
      determining role of the solid support in the SLB-formation process. The presence
      of calcium was found to have a much more pronounced influence on the lipid
      deposition process on mica than on silica. Our results indicate a specific
      calcium-mediated interaction between dioleoylphosphatidylserine molecules and
      mica. In addition, we show that the use of PLL-g-PEG modified tips considerably
      improves the AFM imaging of surface-bound vesicles and bilayer patches and
      evaluate the effects of the AFM tip on the apparent size and shape of these soft
      structures.

PMID- 15731393
TI  - Expression of mutant human epidermal receptor 3 attenuates lung fibrosis and
      improves survival in mice.
AB  - Neuregulin-1 (NRG-1), binding to the human epidermal growth factor receptor
      HER2/HER3, plays a role in pulmonary epithelial cell proliferation and recovery
      from injury in vitro. We hypothesized that activation of HER2/HER3 by NRG-1 would
      also play a role in recovery from in vivo lung injury. We tested this hypothesis
      using bleomycin lung injury of transgenic mice incapable of signaling through
      HER2/HER3 due to lung-specific dominant-negative HER3 (DNHER3) expression. In
      animals expressing DNHER3, protein leak, cell infiltration, and NRG-1 levels in
      bronchoalveolar lavage fluid increased after injury, similar to that in
      nontransgenic littermate control animals. However, HER2/HER3 was not activated,
      and DNHER3 animals displayed fewer lung morphological changes at 10 and 21 days
      after injury (P = 0.01). In addition, they contained 51% less collagen in injured
      lungs (P = 0.04). Transforming growth factor-beta1 did not increase in
      bronchoalveolar lavage fluid from DNHER3 mice compared with nontransgenic
      littermate mice (P = 0.001), suggesting that a mechanism for the decreased
      fibrosis was lack of transforming growth factor-beta1 induction in DNHER3 mice.
      Severe lung injury (0.08 units bleomycin) resulted in 80% mortality of
      nontransgenic mice, but only 35% mortality of DNHER3 transgenic mice (P = 0.04).
      Thus inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and
      improves survival.

PMID- 15731392
TI  - Membrane-Induced Structure of Scyliorhinin I: A Dual NK1/NK2 Agonist.
AB  - Scyliorhinin I, a linear decapeptide, is the only known tachykinin that shows
      high affinity for both NK-1 and NK-2 binding sites and low affinity for NK-3
      binding sites. As a first step to understand the structure-activity relationship,
      we report the membrane-induced structure of scyliorhinin I with the aid of
      circular dichroism and 2D-(1)H NMR spectroscopy. Sequence specific resonance
      assignments of protons have been made from correlation spectroscopy (TOCSY, DQF
      COSY) and NOESY spectroscopy. The interproton distance constraints and dihedral
      angle constraints have been utilized to generate a family of structures using
      DYANA. The superimposition of 20 final structures has been reported with backbone
      pairwise root mean-square deviation of 0.38 +/- 0.19 A. The results show that
      scyliorhinin I exists in a random coil state in aqueous environments, whereas
      helical conformation is induced toward the C-terminal region of the peptide (D4
      M10) in the presence of dodecyl phosphocholine micelles. Analysis of NMR data is
      suggestive of the presence of a 3(10)-helix that is in equilibrium with an alpha
      helix in this region from residue 4 to 10. An extended highly flexible N-terminus
      of scyliorhinin I displays some degree of order and a possible turn structure.
      Observed conformational features have been compared with respect to that of
      substance P and neurokinin A, which are endogenous agonists of NK-1 and NK-2
      receptors, respectively.

PMID- 15731394
TI  - Extracellular water: greater expansion with age in African Americans.
AB  - Aging is associated with the onset of chronic diseases that lead to pathological
      expansion of the extracellular water (ECW) compartment. Healthy aging, in the
      absence of disease, is also reportedly accompanied by a relative expansion of the
      ECW compartment, although the studies on which this observation is based are few
      in number, applied different ECW measurement methods, included small ethnically
      homogeneous subject samples, and failed to adjust ECW for non-age-related
      influencing factors. The aim of the current study was to examine, in a large (n =
      1,538) ethnically diverse [African American (AA), Asian, Caucasian, Hispanic]
      subject group the cross-sectional relationships between ECW and age after
      controlling first for other potential factors that may influence fluid
      distribution. ECW and intracellular water (ICW) were derived from measured total
      body water (isotope dilution) and potassium (40K whole body counting). The cross
      sectional relationships between ECW, ICW, and ECW/ICW (E/I), and age were
      developed using multiple regression modelling methods. Body weight, weight
      squared, height, age, sex, race, and interactions were all significant ECW
      predictors. The slope of the observed race x age interaction was significantly
      greater in AA (beta = 0.0005, P = 0.005) than in the three other race groups.
      Race, sex, and age differences in fluid distribution persisted after adjusting
      for body composition in a subgroup (n = 994) with dual-energy X-ray
      absorptiometry lean soft tissue and fat measurements. A relative ECW expansion
      (i.e., E/I) was present with greater age in most sex-race groups, although the
      effect was not significantly larger in AA males (P > 0.05) compared with the
      other race groups, except Asians (P < 0.05). For females, a larger E/I-age effect
      was found in AA compared with the other race groups, but only the comparison
      against Hispanics was significant (P < 0.05). The ECW compartment and E/I are
      thus variably larger, according to race, in healthy older subjects independent of
      sex, lean soft tissue, and fat mass.

PMID- 15731395
TI  - Carotid distensibility, baroreflex sensitivity, and orthostatic stress.
AB  - In this study, we tested the hypothesis that carotid arteries undergo rapid
      changes in distensibility on moving from the supine to head-up tilt (HUT)
      postures and, subsequently, that this change in carotid distensibility (cDa)
      might be associated with concurrent reductions in cardiovagal baroreflex
      sensitivity (BRS). Thus the effect of posture on carotid vascular mechanics and
      cardiovagal BRS with consideration for altered central hemodynamics (i.e., stroke
      volume; Doppler ultrasound) was examined. Carotid pulse pressure (cPP; Millar
      transducer) and contralateral B-mode ultrasound images were assessed at the
      carotid artery during supine and 60 degrees HUT postures. From these measures,
      cDa was calculated at 5-mmHg pressure increments experienced during the cardiac
      cycle (n = 6). cPP (n = 9) was not different in the two postures. A smaller
      stroke volume being ejected into a smaller carotid artery in HUT explained the
      maintenance of cPP in HUT. Also, compared with supine, cDa was reset to a lower
      level in HUT (main effect of posture; P < 0.05). Cardiovagal BRS (sequence
      method) was diminished in HUT vs. supine (P < 0.05). A positive correlation was
      observed between the tilt-induced changes in maximal cDa (in early systole) and
      cardiovagal BRS (r2 = 0.75; P < 0.05), but there was little predictive
      relationship between changes in cPP, systolic vessel dimensions, or average cDa
      and the corresponding change in BRS. The present results indicate that HUT
      elicits rapid changes in carotid artery mechanics and further suggest that
      reductions in the maximal cDa measured in early systole contribute to reduced
      cardiovagal BRS with HUT.

PMID- 15731396
TI  - Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac
      myocytes.
AB  - Although the prevailing view of mechanoelectric feedback (MEF) in the heart is in
      terms of longitudinal cell stretch, other mechanical forces are considerable
      during the cardiac cycle, including intramyocardial pressure and shear stress.
      Their contribution to MEF is largely unknown. In this study, mechanical stimuli
      in the form of localized fluid jet pulses were applied to neonatal rat
      ventricular cells cultured as confluent monolayers. Such pulses result in
      pressure and shear stresses (but not longitudinal stretch) in the monolayer at
      the point of impingement. The goal was to determine whether these mechanical
      stimuli can trigger excitation, initiate a propagated wave, and induce reentry.
      Cells were stained with the voltage-sensitive dye RH237, and multi-site optical
      mapping was used to record the spread of electrical activity in isotropic and
      anisotropic monolayers. Pulses (10 ms) with velocities ranging from 0.3 to 1.8
      m/s were applied from a 0.4-mm diameter nozzle located 1 mm above the cell
      monolayer. Fluid jet pulses resulted in circular wavefronts that propagated
      radially from the stimulus site. The likelihood for mechanical stimulation was
      quantified as an average stimulus success rate (ASSR). ASSR increased with jet
      amplitude and time waited between stimuli and decreased with the application of
      gadolinium and streptomycin, blockers of stretch-activated channels, but not with
      nifedipine, a blocker of the L-type Ca channel. Absence of cellular injury was
      confirmed by smooth propagation maps and propidium iodide stains. In rare
      instances, the mechanical pulse resulted in the induction of reentrant activity.
      We conclude that mechanical stimuli other than stretch can evoke action
      potentials, propagated activity, and reentrant arrhythmia in two-dimensional
      sheets of cardiac cells.

PMID- 15731397
TI  - Perinatal hyperoxia for 14 days increases nerve conduction time and the acute
      unitary response to hypoxia of rat carotid body chemoreceptors.
AB  - Hyperoxia in the immediate perinatal period, but not in adult life, is associated
      with a life-long impairment of the ventilatory response to acute hypoxia. This
      effect is attributed to a functional impairment of peripheral chemoreceptors,
      including a reduction in the number of chemoreceptor afferent fibers and a
      reduction in "whole nerve" afferent activity. The purpose of the present study
      was to assess the activity levels of single chemoreceptor units in the immediate
      posthyperoxic period to determine whether functional impairment extended to
      single chemoreceptor units and whether the impairment was only induced by
      hyperoxia exposure in the immediate postnatal period. Two groups of rat pups were
      exposed to 60% inspired O2 fraction for 2 wk at ages 0-14 days and 14-28 days, at
      which time single-unit activities were isolated and recorded in vitro. Compared
      with control pups, hyperoxia-treated pups had a 10-fold reduction in baseline
      (normoxia) spiking activity. Peak unit responses to 12, 5, and 0% O2 were reduced
      and nerve conduction time was significantly slower in both hyperoxia-treated
      groups compared with control groups. We conclude that 1) hyperoxia greatly
      reduces single-unit chemoreceptor activities during normoxia and acute hypoxia,
      2) the treatment effect is not limited to the immediate newborn period, and 3) at
      least part of the impairment may be due to changes in the afferent axonal
      excitability.

PMID- 15731398
TI  - Changes in the human muscle force-velocity relationship in response to resistance
      training and subsequent detraining.
AB  - Previous studies show that cessation of resistance training, commonly known as
      "detraining," is associated with strength loss, decreased neural drive, and
      muscular atrophy. Detraining may also increase the expression of fast muscle
      myosin heavy chain (MHC) isoforms. The present study examined the effect of
      detraining subsequent to resistance training on contractile performance during
      slow-to-medium velocity isokinetic muscle contraction vs. performance of maximal
      velocity "unloaded" limb movement (i.e., no external loading of the limb).
      Maximal knee extensor strength was measured in an isokinetic dynamometer at 30
      and 240 degrees/s, and performance of maximal velocity limb movement was measured
      with a goniometer during maximal unloaded knee extension. Muscle cross-sectional
      area was determined with MRI. Electromyographic signals were measured in the
      quadriceps and hamstring muscles. Twitch contractions were evoked in the passive
      vastus lateralis muscle. MHC isoform composition was determined with SDS-PAGE.
      Isokinetic muscle strength increased 18% (P < 0.01) and 10% (P < 0.05) at slow
      and medium velocities, respectively, along with gains in muscle cross-sectional
      area and increased electromyogram in response to 3 mo of resistance training.
      After 3 mo of detraining these gains were lost, whereas in contrast maximal
      unloaded knee extension velocity and power increased 14% (P < 0.05) and 44% (P <
      0.05), respectively. Additionally, faster muscle twitch contractile properties
      along with an increased and decreased amount of MHC type II and MHC type I
      isoforms, respectively, were observed. In conclusion, detraining subsequent to
      resistance training increases maximal unloaded movement speed and power in
      previously untrained subjects. A phenotypic shift toward faster muscle MHC
      isoforms (I --> IIA --> IIX) and faster electrically evoked muscle contractile
      properties in response to detraining may explain the present results.

PMID- 15731399
TI  - Hepatic beta-oxidation and carnitine palmitoyltransferase I in neonatal pigs
      after dietary treatments of clofibric acid, isoproterenol, and medium-chain
      triglycerides.
AB  - A suckling piglet model was used to study nutritional and pharmacologic means of
      stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets
      containing either long- or medium-chain triglycerides (LCT or MCT). The long
      chain control diet was supplemented further with clofibric acid (0.5%) or
      isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate
      increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1
      (14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive
      carnitine palmitoyltransferase (CPT I) activity increased 64% (P < 0.05) in pigs
      receiving clofibrate. Increased CPT I activity was not congruent with changes in
      message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when
      assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were
      affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively,
      these findings indicate that clofibrate effectively induced hepatic CPT activity
      concomitant with increased fatty acid beta-oxidation.

PMID- 15731400
TI  - Reduced feeding response to muscimol and neuropeptide Y in senescent F344 rats.
AB  - Many mammals experience spontaneous declines in their food intake and body weight
      near the end of life, a stage we refer to as senescence. We have previously
      demonstrated that senescent rats have blunted food intake responses to
      intracerebroventricular injections of neuropeptide Y (NPY). In the present study,
      we tested the hypothesis that responsiveness to GABA, a putative potentiator of
      NPY's effect, is also diminished. Young and old male F344 rats received
      injections of NPY, muscimol, (MUS, a GABA-A receptor agonist), combinations of
      these two agents, and vehicle [artificial cerebrospinal fluid (aCSF)] into the
      hypothalamic paraventricular nucleus (PVN). Both young and old presenescent rats
      increased their food intake in response to NPY, MUS, and the combination of the
      two (in comparison to injections of aCSF). The combination treatment was
      generally more effective than either NPY or MUS alone. These data are consistent
      with suggestions that both NPY and GABA play a role in the regulation of feeding
      behavior. Senescent rats exhibited an attenuated NPY-induced food intake, no
      increase in response to MUS, and a response to NPY + MUS that was no larger than
      that of NPY alone. We conclude that PVN injections of GABA, as well as NPY, are
      less effective in stimulating feeding in senescent rats and suggest that
      alterations in their signaling pathways play a role in the involuntary feeding
      decrease seen near the end of life.

PMID- 15731401
TI  - NK1 receptor activation in rat rostral ventrolateral medulla selectively
      attenuates somato-sympathetic reflex while antagonism attenuates sympathetic
      chemoreflex.
AB  - The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the
      rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic
      sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic
      reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and
      artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either
      the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5-11) (DiMe-SP) or the
      highly selective NK1 agonist [Sar9, Met (O(2))11]SP into the RVLM resulted in an
      increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity.
      The effects of [Sar9, Met (O(2))11]SP were blocked by the selective nonpeptide
      NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically
      attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation,
      while leaving the baroreflex and chemoreflex unaffected. This effect was again
      blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708
      significantly attenuated the sympathoexcitatory response to hypoxia but had no
      effect on baseline respiratory function. Our findings suggest that substance P
      and the NK1 receptor play a significant role in the cardiorespiratory reflexes
      integrated within the RVLM.

PMID- 15731402
TI  - Mice with MCH ablation resist diet-induced obesity through strain-specific
      mechanisms.
AB  - Genetics and environment contribute to the development of obesity, in both humans
      and rodents. However, the potential interaction between genes important in energy
      balance, strain background, and dietary environment has been only minimally
      explored. We investigated the effects of genetic ablation of melanin
      concentrating hormone (MCH), a neuropeptide with a key role in energy balance,
      with chow and a high-fat diet (HFD) in two different mouse strains, one obesity
      prone (C57BL/6) and the other obesity-resistant (129). Substantial differences
      were seen in wild-type (WT) animals of different strains. 129 animals had
      significantly lower levels of spontaneous locomotor activity than C57BL/6;
      however, 129 mice gained less weight on both chow and HFD. In both strains,
      deletion of MCH led to attenuated weight gain compared with WT counterparts, an
      effect secondary to increased energy expenditure. In both strains, feeding a HFD
      led to further increases in energy expenditure in both WT and MCH-KO mice;
      however, this increase was more pronounced in 129 mice. In addition, mice lacking
      MCH have a phenotype of increased locomotor activity, an effect also seen in both
      strains. The relative increase in activity in MCH(-/-) mice is modest in animals
      fed chow but increases substantially when animals are placed on HFD. These
      studies reinforce the important role of MCH in energy homeostasis and indicate
      that MCH is a plausible target for antiobesity therapy.

PMID- 15731403
TI  - Sympathetic denervation does not prevent a reduction in fat pad size of rats or
      mice treated with peripherally administered leptin.
AB  - Leptin increases sympathetic nervous system (SNS) activity in brown adipose
      tissue and renal nerves. Experiments described here tested whether SNS
      innervation is required for peripheral, physiological concentrations of leptin to
      reduce body fat. In experiment 1, one epididymal (EPI) fat pad was
      sympathectomized by local injection of 6-hydroxydopamine (6OHDA) in C57BL/6 mice
      that were then infused for 13 days with PBS or 10 microg leptin/day from an
      intraperitoneal miniosmotic pump. Surprisingly, EPI denervation increased total
      body fat of PBS-infused mice but leptin decreased the size of both injected and
      noninjected EPI pads in 6OHDA mice. Experiment 2 was identical except for the use
      of male Sprague-Dawley rats that were infused with 50 microg leptin/day. Leptin
      had little effect on EPI weight or norepinephrine (NE) content, but denervation
      of one EPI pad decreased the effect of leptin on intact EPI, inguinal and
      retroperitoneal (RP) fat and increased the size of the mesenteric fat pad.
      Experiment 3 included groups in which either one EPI or one RP pad was
      denervated. RP denervation reduced RP NE content but did not prevent a leptin
      induced reduction in fat pad mass. Therefore, the SNS is not required for low
      doses of leptin to reduce body fat. EPI denervation significantly increased
      adipocyte number in contralateral EPI and RP fat pads and this was prevented by
      leptin. These changes in intact pads of rats with one denervated fat pad imply
      communication between fat depots and suggest that both leptin and the SNS
      regulate the size of individual depots.

PMID- 15731404
TI  - Retinoic acid controls the bilateral symmetry of somite formation in the mouse
      embryo.
AB  - A striking characteristic of vertebrate embryos is their bilaterally symmetric
      body plan, which is particularly obvious at the level of the somites and their
      derivatives such as the vertebral column. Segmentation of the presomitic mesoderm
      must therefore be tightly coordinated along the left and right embryonic sides.
      We show that mutant mice defective for retinoic acid synthesis exhibit delayed
      somite formation on the right side. Asymmetric somite formation correlates with a
      left-right desynchronization of the segmentation clock oscillations. These data
      implicate retinoic acid as an endogenous signal that maintains the bilateral
      synchrony of mesoderm segmentation, and therefore controls bilateral symmetry, in
      vertebrate embryos.

PMID- 15731405
TI  - Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in
      mice.
AB  - Loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) is an
      epigenetic alteration that results in a modest increase in IGF2 expression, and
      it is present in the normal colonic mucosa of about 30% of patients with
      colorectal cancer. To investigate its role in intestinal tumorigenesis, we
      created a mouse model of Igf2 LOI by crossing female H19+/- mice with male
      Apc+/Min mice. Mice with LOI developed twice as many intestinal tumors as did
      control littermates. Notably, these mice also showed a shift toward a less
      differentiated normal intestinal epithelium, reflected by an increase in crypt
      length and increased staining with progenitor cell markers. A similar shift in
      differentiation was seen in the normal colonic mucosa of humans with LOI. Thus,
      altered maturation of nonneoplastic tissue may be one mechanism by which
      epigenetic changes affect cancer risk.

PMID- 15731406
TI  - U-Pb ages from the neoproterozoic Doushantuo Formation, China.
AB  - U-Pb zircon dates from volcanic ash beds within the Doushantuo Formation (China)
      indicate that its deposition occurred between 635 and 551 million years ago. The
      base records termination of the global-scale Marinoan glaciation and is coeval
      with similar dated rocks from Namibia, indicating synchronous deglaciation.
      Carbon isotopic and sequence-stratigraphic data imply that the spectacular animal
      fossils of the Doushantuo Formation are for the most part younger than 580
      million years old. The uppermost Doushantuo Formation contains a pronounced
      negative carbonate carbon isotopic excursion, which we interpret as a global
      event at circa 551 million years ago.

PMID- 15731409
TI  - Astrophysics. Giant neutron-star flare blitzes the galaxy with gamma rays.

PMID- 15731408
TI  - French public research--saved?

PMID- 15731407
TI  - Crystal structure of the malaria vaccine candidate apical membrane antigen 1.
AB  - Apical membrane antigen 1 from Plasmodium is a leading malaria vaccine candidate.
      The protein is essential for host-cell invasion, but its molecular function is
      unknown. The crystal structure of the three domains comprising the ectoplasmic
      region of the antigen from P. vivax, solved at 1.8 angstrom resolution, shows
      that domains I and II belong to the PAN motif, which defines a superfamily of
      protein folds implicated in receptor binding. We also mapped the epitope of an
      invasion-inhibitory monoclonal antibody specific for the P. falciparum ortholog
      and modeled this to the structure. The location of the epitope and current
      knowledge on structure-function correlations for PAN domains together suggest a
      receptor-binding role during invasion in which domain II plays a critical part.
      These results are likely to aid vaccine and drug design.

PMID- 15731411
TI  - South Korea. Radical reforms would shake up leading science institute.

PMID- 15731410
TI  - Human origins. Battle erupts over the 'hobbit' bones.

PMID- 15731412
TI  - National Institutes of Health. NCI gears up for cancer genome project.

PMID- 15731413
TI  - Environmental science. Forging a global network to watch the planet.

PMID- 15731414
TI  - Drug safety. FDA panel urges caution on many anti-inflammatory drugs.

PMID- 15731415
TI  - HIV/AIDS. Experts question danger of 'AIDS superbug'.

PMID- 15731416
TI  - Ecology. Reviving Iraq's wetlands.

PMID- 15731417
TI  - American Association for the Advancement of Science meeting. Ocean warming model
      again points to a human touch.

PMID- 15731418
TI  - American Association for the Advancement of Science meeting. More infectious
      diseases emerge in North.

PMID- 15731419
TI  - American Association for the Advancement of Science meeting. Whaling endangers
      more than whales.

PMID- 15731421
TI  - Archaeology. Ancient Alexandria emerges, by land and by sea.

PMID- 15731420
TI  - American Association for the Advancement of Science meeting. DNA tells story of
      heart drug failure.

PMID- 15731422
TI  - Archaeology. Oxford center raises controversy.

PMID- 15731423
TI  - Radio astronomy. Bristling with promise.

PMID- 15731424
TI  - The emergence of the ERC.

PMID- 15731425
TI  - Protecting privacy of human subjects.

PMID- 15731426
TI  - Autism and deficits in attachment behavior.

PMID- 15731427
TI  - Comment on "Epitaxial BiFeO3 multiferroic thin film heterostructures".

PMID- 15731429
TI  - Space science. Crossroad for European space activity.

PMID- 15731430
TI  - Neuroscience. Making synapses: a balancing act.

PMID- 15731431
TI  - History of science. "How science survived"--medieval manuscripts as fossils.

PMID- 15731432
TI  - Physics. The road to quantum computing.

PMID- 15731434
TI  - Evolution. Ernst Mayr (1904-2005).

PMID- 15731433
TI  - Microbiology. A pathogen attacks while keeping up defense.

PMID- 15731435
TI  - New perspectives on ancient Mars.
AB  - Mars was most active during its first billion years. The core, mantle, and crust
      formed within approximately 50 million years of solar system formation. A
      magnetic dynamo in a convecting fluid core magnetized the crust, and the global
      field shielded a more massive early atmosphere against solar wind stripping. The
      Tharsis province became a focus for volcanism, deformation, and outgassing of
      water and carbon dioxide in quantities possibly sufficient to induce episodes of
      climate warming. Surficial and near-surface water contributed to regionally
      extensive erosion, sediment transport, and chemical alteration. Deep hydrothermal
      circulation accelerated crustal cooling, preserved variations in crustal
      thickness, and modified patterns of crustal magnetization.

PMID- 15731437
TI  - How long is the day on Saturn?
AB  - Determining a planet's rotation period can be difficult if the planet lacks a
      solid surface. However, for planets with an internal magnetic field, emissions at
      radio wavelengths are modulated by the planet's rotation rate. The latest results
      from the Cassini spacecraft seem to indicate that Saturn's rotation rate has
      slowed down by 6 minutes since the Voyager 1 and 2 spacecraft flew by the planet
      in 1980 and 1981, but it is unclear whether a slowdown has in fact occurred.
      Future data collected by Cassini may be able to resolve the question.

PMID- 15731438
TI  - Saturn's variable magnetosphere.
AB  - Since the Cassini spacecraft reached Saturn's orbit in 2004, its instruments have
      been sending back a wealth of data on the planet's magnetosphere (the region
      dominated by the magnetic field of the planet). In this Viewpoint, we discuss
      some of these results, which are reported in a collection of reports in this
      issue. The magnetosphere is shown to be highly variable and influenced by the
      planet's rotation, sources of plasma within the planetary system, and the solar
      wind. New insights are also gained into the chemical composition of the
      magnetosphere, with surprising results. These early results from Cassini's first
      orbit around Saturn bode well for the future as the spacecraft continues to orbit
      the planet.

PMID- 15731439
TI  - Cassini Imaging Science: initial results on Saturn's rings and small satellites.
AB  - Images acquired of Saturn's rings and small moons by the Cassini Imaging Science
      Subsystem (ISS) during the first 9 months of Cassini operations at Saturn have
      produced many new findings. These include new saturnian moons; refined orbits of
      new and previously known moons; narrow diffuse rings in the F-ring region and
      embedded in gaps within the main rings; exceptionally fine-scale ring structure
      in moderate- to high-optical depth regions; new estimates for the masses of ring
      region moons, as well as ring particle properties in the Cassini division,
      derived from the analysis of linear density waves; ring particle albedos in
      select ring regions; and never-before-seen phenomena within the rings.

PMID- 15731440
TI  - Cassini Imaging Science: initial results on Phoebe and Iapetus.
AB  - The Cassini Imaging Science Subsystem acquired high-resolution imaging data on
      the outer Saturnian moon, Phoebe, during Cassini's close flyby on 11 June 2004
      and on Iapetus during a flyby on 31 December 2004. Phoebe has a heavily cratered
      and ancient surface, shows evidence of ice near the surface, has distinct
      layering of different materials, and has a mean density that is indicative of an
      ice-rock mixture. Iapetus's dark leading side (Cassini Regio) is ancient, heavily
      cratered terrain bisected by an equatorial ridge system that reaches 20
      kilometers relief. Local albedo variations within and bordering Cassini Regio
      suggest mass wasting of ballistically deposited material, the origin of which
      remains unknown.

PMID- 15731441
TI  - Cassini Imaging Science: initial results on Saturn's atmosphere.
AB  - The Cassini Imaging Science Subsystem (ISS) began observing Saturn in early
      February 2004. From analysis of cloud motions through early October 2004, we
      report vertical wind shear in Saturn's equatorial jet and a maximum wind speed of
      approximately 375 meters per second, a value that differs from both Hubble Space
      Telescope and Voyager values. We also report a particularly active narrow
      southern mid-latitude region in which dark ovals are observed both to merge with
      each other and to arise from the eruptions of large, bright storms. Bright storm
      eruptions are correlated with Saturn's electrostatic discharges, which are
      thought to originate from lightning.

PMID- 15731442
TI  - Oxygen ions observed near Saturn's A ring.
AB  - Ions were detected in the vicinity of Saturn's A ring by the Ion and Neutral Mass
      Spectrometer (INMS) instrument onboard the Cassini Orbiter during the
      spacecraft's passage over the rings. The INMS saw signatures of molecular and
      atomic oxygen ions and of protons, thus demonstrating the existence of an
      ionosphere associated with the A ring. A likely explanation for these ions is
      photoionization by solar ultraviolet radiation of neutral O2 molecules associated
      with a tenuous ring atmosphere. INMS neutral measurements made during the ring
      encounter are dominated by a background signal.

PMID- 15731444
TI  - Cassini magnetometer observations during Saturn orbit insertion.
AB  - Cassini's successful orbit insertion has provided the first examination of
      Saturn's magnetosphere in 23 years, revealing a dynamic plasma and magnetic
      environment on short and long time scales. There has been no noticeable change in
      the internal magnetic field, either in its strength or its near-alignment with
      the rotation axis. However, the external magnetic field is different compared
      with past spacecraft observations. The current sheet within the magnetosphere is
      thinner and more extended, and we observed small diamagnetic cavities and ion
      cyclotron waves of types that were not reported before.

PMID- 15731443
TI  - Composition and dynamics of plasma in Saturn's magnetosphere.
AB  - During Cassini's initial orbit, we observed a dynamic magnetosphere composed
      primarily of a complex mixture of water-derived atomic and molecular ions. We
      have identified four distinct regions characterized by differences in both bulk
      plasma properties and ion composition. Protons are the dominant species outside
      about 9 RS (where RS is the radial distance from the center of Saturn), whereas
      inside, the plasma consists primarily of a corotating comet-like mix of water
      derived ions with approximately 3% N+. Over the A and B rings, we found an
      ionosphere in which O2+ and O+ are dominant, which suggests the possible
      existence of a layer of O2 gas similar to the atmospheres of Europa and Ganymede.

PMID- 15731445
TI  - Dynamics of Saturn's magnetosphere from MIMI during Cassini's orbital insertion.
AB  - The Magnetospheric Imaging Instrument (MIMI) onboard the Cassini spacecraft
      observed the saturnian magnetosphere from January 2004 until Saturn orbit
      insertion (SOI) on 1 July 2004. The MIMI sensors observed frequent energetic
      particle activity in interplanetary space for several months before SOI. When the
      imaging sensor was switched to its energetic neutral atom (ENA) operating mode on
      20 February 2004, at approximately 10(3) times Saturn's radius RS (0.43
      astronomical units), a weak but persistent signal was observed from the
      magnetosphere. About 10 days before SOI, the magnetosphere exhibited a day-night
      asymmetry that varied with an approximately 11-hour periodicity. Once Cassini
      entered the magnetosphere, in situ measurements showed high concentrations of H+,
      H2+, O+, OH+, and H2O+ and low concentrations of N+. The radial dependence of ion
      intensity profiles implies neutral gas densities sufficient to produce high loss
      rates of trapped ions from the middle and inner magnetosphere. ENA imaging has
      revealed a radiation belt that resides inward of the D ring and is probably the
      result of double charge exchange between the main radiation belt and the upper
      layers of Saturn's exosphere.

PMID- 15731446
TI  - Composition of saturnian stream particles.
AB  - During Cassini's approach to Saturn, the Cosmic Dust Analyser (CDA) discovered
      streams of tiny (less than 20 nanometers) high-velocity (approximately 100
      kilometers per second) dust particles escaping from the saturnian system. A
      fraction of these impactors originated from the outskirts of Saturn's dense A
      ring. The CDA time-of-flight mass spectrometer recorded 584 mass spectra from the
      stream particles. The particles consist predominantly of oxygen, silicon, and
      iron, with some evidence of water ice, ammonium, and perhaps carbon. The stream
      particles primarily consist of silicate materials, and this implies that the
      particles are impurities from the icy ring material rather than the ice particles
      themselves.

PMID- 15731447
TI  - Bacterial injectisomes: needle length does matter.
AB  - Many pathogenic bacteria use a type III secretion nanomachine (an injectisome) to
      deliver virulence proteins into the cytosol of their eukaryotic host cells. Most
      injectisomes possess a stiff needlelike structure of a genetically defined
      length. We found that a minimal needle length was required for efficient
      functioning of the Yersinia enterocolitica injectisome. This minimal needle
      length correlated with the length of the major adhesin at the bacterial surface.
      The needle may be required for triggering type III secretion, and its length may
      have evolved to match specific structures at the bacterial and host cell
      surfaces.

PMID- 15731449
TI  - The use of transit timing to detect terrestrial-mass extrasolar planets.
AB  - Future surveys for transiting extrasolar planets are expected to detect hundreds
      of jovian-mass planets and tens of terrestrial-mass planets. For many of these
      newly discovered planets, the intervals between successive transits will be
      measured with an accuracy of 0.1 to 100 minutes. We show that these timing
      measurements will allow for the detection of additional planets in the system
      (not necessarily transiting) by their gravitational interaction with the
      transiting planet. The transit-time variations depend on the mass of the
      additional planet, and in some cases terrestrial-mass planets will produce a
      measurable effect. In systems where two planets are seen to transit, the density
      of both planets can be determined without radial-velocity observations.

PMID- 15731448
TI  - Axonopathy and transport deficits early in the pathogenesis of Alzheimer's
      disease.
AB  - We identified axonal defects in mouse models of Alzheimer's disease that preceded
      known disease-related pathology by more than a year; we observed similar axonal
      defects in the early stages of Alzheimer's disease in humans. Axonal defects
      consisted of swellings that accumulated abnormal amounts of microtubule
      associated and molecular motor proteins, organelles, and vesicles. Impairing
      axonal transport by reducing the dosage of a kinesin molecular motor protein
      enhanced the frequency of axonal defects and increased amyloid-beta peptide
      levels and amyloid deposition. Reductions in microtubule-dependent transport may
      stimulate proteolytic processing of beta-amyloid precursor protein, resulting in
      the development of senile plaques and Alzheimer's disease.

PMID- 15731450
TI  - Unveiling extensive clouds of dark gas in the solar neighborhood.
AB  - From the comparison of interstellar gas tracers in the solar neighborhood (HI and
      CO lines from the atomic and molecular gas, dust thermal emission, and g rays
      from cosmic-ray interactions with gas), we unveil vast clouds of cold dust and
      dark gas, invisible in HI and CO but detected in gamma rays. They surround all
      the nearby CO clouds and bridge the dense cores to broader atomic clouds, thus
      providing a key link in the evolution of interstellar clouds. The relation
      between the masses in the molecular, dark, and atomic phases in the local clouds
      implies a dark gas mass in the Milky Way comparable to the molecular one.

PMID- 15731451
TI  - Simultaneous state measurement of coupled Josephson phase qubits.
AB  - One of the many challenges of building a scalable quantum computer is single-shot
      measurement of all the quantum bits (qubits). We have used simultaneous single
      shot measurement of coupled Josephson phase qubits to directly probe interaction
      of the qubits in the time domain. The concept of measurement crosstalk is
      introduced, and we show that its effects are minimized by careful adjustment of
      the timing of the measurements. We observe the antiphase oscillation of the two
      qubit 01 and 10 states, consistent with quantum mechanical entanglement of these
      states, thereby opening the possibility for full characterization of multiqubit
      gates and elementary quantum algorithms.

PMID- 15731452
TI  - Evidence for a great medieval earthquake (~1100 A.D.) in the central Himalayas,
      Nepal.
AB  - The Himalayan orogen has produced three thrust earthquakes with moment magnitude
      (Mw) 7.8 to 8.5 during the past century, yet no surface ruptures associated with
      these great earthquakes have been documented. Here, we present paleoseismic
      evidence from east central Nepal that, since approximately 700 A.D., a single
      earthquake ruptured the Frontal Thrust fault at approximately 1100 A.D., with a
      surface displacement of approximately 17 (+5/-3) meters and a lateral extent and
      size that could have exceeded 240 kilometers and approximately Mw 8.8,
      respectively. Ruptures associated with Mw <8.2 events would contribute to the
      frontal Himalayas folding but would stop before reaching the surface. These
      findings could require substantial modifications to current regional seismic
      hazard models.

PMID- 15731453
TI  - How science survived: medieval manuscripts' "demography" and classic texts'
      extinction.
AB  - Determining what fraction of texts and manuscripts have survived from Antiquity
      and the Middle Ages has been highly problematic. Analyzing the transmission of
      texts as the "paleodemography" of their manuscripts yields definite and
      surprisingly high estimates. Parchment copies of the foremost medieval textbooks
      on arithmetical and calendrical calculation closely fit age distributions
      expected for populations with logistic growth and manuscripts with exponential
      survivorship. The estimated half-lives of copies agree with Bischoff's
      paleographically based suggestion that roughly one in seven manuscripts survive
      in some form from ninth-century Carolingian workshops. On this basis, many if not
      most of the leading technical titles circulating in Latin probably survived, even
      from late Antiquity.

PMID- 15731454
TI  - The restoration potential of the Mesopotamian marshes of Iraq.
AB  - Uncontrolled releases of Tigris and Euphrates River waters after the 2003 war
      have partially restored some former marsh areas in southern Iraq, but restoration
      is failing in others because of high soil and water salinities. Nearly 20% of the
      original 15,000-square-kilometer marsh area was reflooded by March 2004, but the
      extent of marsh restoration is unknown. High-quality water, nonsaline soils, and
      the densest native vegetation were found in the only remaining natural marsh, the
      Al-Hawizeh, located on the Iranian border. Although substantially reduced in area
      and under current threat of an Iranian dike, it has the potential to be a native
      repopulation center for the region. Rapid reestablishment, high productivity, and
      reproduction of native flora and fauna in reflooded former marsh areas indicate a
      high probability for successful restoration, provided the restored wetlands are
      hydraulically designed to allow sufficient flow of noncontaminated water and
      flushing of salts through the ecosystem.

PMID- 15731456
TI  - Optimization of virulence functions through glucosylation of Shigella LPS.
AB  - Shigella, the leading cause of bacillary dysentery, uses a type III secretion
      system (TTSS) to inject proteins into human cells, leading to bacterial invasion
      and a vigorous inflammatory response. The bacterium is protected against the
      response by the O antigen of lipopolysaccharide (LPS) on its surface. We show
      that bacteriophage-encoded glucosylation of Shigella O antigen, the basis of
      different serotypes, shortens the LPS molecule by around half. This enhances TTSS
      function without compromising the protective properties of the LPS. Thus, LPS
      glucosylation promotes bacterial invasion and evasion of innate immunity, which
      may have contributed to the emergence of serotype diversity in Shigella.

PMID- 15731457
TI  - NMR structure of Mistic, a membrane-integrating protein for membrane protein
      expression.
AB  - Although structure determination of soluble proteins has become routine, our
      understanding of membrane proteins has been limited by experimental bottlenecks
      in obtaining both sufficient yields of protein and ordered crystals. Mistic is an
      unusual Bacillus subtilis integral membrane protein that folds autonomously into
      the membrane, bypassing the cellular translocon machinery. Using paramagnetic
      probes, we determined by nuclear magnetic resonance (NMR) spectroscopy that the
      protein forms a helical bundle with a surprisingly polar lipid-facing surface.
      Additional experiments suggest that Mistic can be used for high-level production
      of other membrane proteins in their native conformations, including many
      eukaryotic proteins that have previously been intractable to bacterial
      expression.

PMID- 15731458
TI  - Mechanisms of atrial fibrillation termination by pure sodium channel blockade in
      an ionically-realistic mathematical model.
AB  - The mechanisms by which Na+-channel blocking antiarrhythmic drugs terminate
      atrial fibrillation (AF) remain unclear. Classical "leading-circle" theory
      suggests that Na+-channel blockade should, if anything, promote re-entry. We used
      an ionically-based mathematical model of vagotonic AF to evaluate the effects of
      applying pure Na+-current (I(Na)) inhibition during sustained arrhythmia. Under
      control conditions, AF was maintained by 1 or 2 dominant spiral waves, with
      fibrillatory propagation at critical levels of action potential duration (APD)
      dispersion. I(Na) inhibition terminated AF increasingly with increasing block,
      terminating all AF at 65% block. During 1:1 conduction, I(Na) inhibition reduced
      APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry
      wavelength (by 24%). During AF, I(Na) inhibition increased the size of primary
      rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60%
      I(Na) inhibition) while decreasing generation of secondary wavelets by wavebreak.
      Three mechanisms contributed to I(Na) block-induced AF termination in the model:
      (1) enlargement of the center of rotation beyond the capacity of the
      computational substrate; (2) decreased anchoring to functional obstacles,
      increasing meander and extinction at boundaries; and (3) reduction in the number
      of secondary wavelets that could provide new primary rotors. Optical mapping in
      isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF
      while producing effects qualitatively like those of I(Na) inhibition in the
      mathematical model. We conclude that pure INa inhibition terminates AF, producing
      activation changes consistent with previous clinical and experimental
      observations. These results provide insights into previously enigmatic mechanisms
      of class I antiarrhythmic drug-induced AF termination. The full text of this
      article is available online at http://circres.ahajournals.org

PMID- 15731455
TI  - Genotypic diversity within a natural coastal bacterioplankton population.
AB  - The genomic diversity and relative importance of distinct genotypes within
      natural bacterial populations have remained largely unknown. Here, we analyze the
      diversity and annual dynamics of a group of coastal bacterioplankton (greater
      than 99% 16S ribosomal RNA identity to Vibrio splendidus). We show that this
      group consists of at least a thousand distinct genotypes, each occurring at
      extremely low environmental concentrations (on average less than one cell per
      milliliter). Overall, the genomes show extensive allelic diversity and size
      variation. Individual genotypes rarely recurred in samples, and allelic
      distribution did not show spatial or temporal substructure. Ecological
      considerations suggest that much genotypic and possibly phenotypic variation
      within natural populations should be considered neutral.

PMID- 15731459
TI  - Caveolin-1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro
      and in vivo.
AB  - Mechanotransduction represents an integral part of vascular homeostasis and
      contributes to vascular lesion formation. Previously, we demonstrated a
      mechanosensitive activation of phosphoinositide 3-kinase (PI3-K)/protein kinase B
      (Akt) resulting in p27Kip1 transcriptional downregulation and cell cycle entry of
      vascular smooth muscle cells (VSMC). In this study, we further elucidated the
      signaling from outside-in toward PI3-K/Akt in vitro and in an in vivo model of
      elevated tensile force. When VSMC were subjected to cyclic stretch (0.5 Hz at
      125% resting length), PI3-K, Akt, and Src kinases were found activated.
      Disrupting caveolar structures with beta-cyclodextrin or transfection of VSMC
      with caveolin-1 antisense oligonucleotides (ODN) prevented PI3-K and Akt
      activation and cell cycle entry. Furthermore, PI3-K and Akt were resistant to
      activation when Src kinases were inhibited pharmacologically or by overexpression
      of a kinase-dead c-Src mutant. alpha(V)beta3 integrins were identified to
      colocalize with PI3-K/caveolin-1 complexes, and blockade of alpha(V)beta3
      integrins prevented Akt activation. The central role of caveolin-1 in
      mechanotransduction was further examined in an in vivo model of elevated tensile
      force. Interposition of wild-type (WT) jugular veins into WT carotid arteries
      resulted in a rapid Akt activation within the veins that was almost abolished
      when veins of caveolin-1 knockout (KO) mice were used. Furthermore, late
      neointima formation within the KO veins was significantly reduced. Our study
      provides evidence that PI3-K/Akt is critically involved in mechanotransduction of
      VSMC in vitro and within the vasculature in vivo. Furthermore, caveolin-1 is
      essential for the integrin-mediated activation of PI3-K/Akt.

PMID- 15731460
TI  - Triadin overexpression stimulates excitation-contraction coupling and increases
      predisposition to cellular arrhythmia in cardiac myocytes.
AB  - Triadin 1 (TRD) is an integral membrane protein that associates with the
      ryanodine receptor (RyR2), calsequestrin (CASQ2) and junctin to form a
      macromolecular Ca signaling complex in the cardiac junctional sarcoplasmic
      reticulum (SR). To define the functional role of TRD, we examined the effects of
      adenoviral-mediated overexpression of the wild-type protein (TRD(WT)) or a TRD
      mutant lacking the putative CASQ2 interaction domain residues 200 to 224
      (TRD(Del.200-224)) on intracellular Ca signaling in adult rat ventricular
      myocytes. Overexpression of TRD(WT) reduced the amplitude of I(Ca)- induced Ca
      transients (at 0 mV) but voltage dependency of the Ca transients was markedly
      widened and flattened, such that even small I(Ca) at low and high depolarizations
      triggered maximal Ca transients. The frequency of spontaneous Ca sparks was
      significantly increased in TRD(WT) myocytes, whereas the amplitude of individual
      sparks was reduced. Consistent with these changes in Ca release signals, SR Ca
      content was decreased in TRD(WT) myocytes. Periodic electrical stimulation of
      TRD(WT) myocytes resulted in irregular, spontaneous Ca transients and arrhythmic
      oscillations of the membrane potential. Expression of TRD(Del.200-224) failed to
      produce any of the effects of the wild-type protein. The lipid bilayer technique
      was used to record the activity of single RyR2 channels using microsome samples
      obtained from control, TRD(WT) and TRD(Del.200-224) myocytes. Elevation of
      TRD(WT) levels increased the open probability of RyR2 channels, whereas
      expression of the mutant protein did not affect RyR2 activity. We conclude that
      TRD enhances cardiac excitation-contraction coupling by directly stimulating the
      RyR2. Interaction of TRD with RyR2 may involve amino acids 200 to 224 in C
      terminal domain of TRD.

PMID- 15731461
TI  - Identification of hypertension-related genes through an integrated genomic
      transcriptomic approach.
AB  - In search for the genetic basis of hypertension, we applied an integrated genomic
      transcriptomic approach to identify genes involved in the pathogenesis of
      hypertension in the Sabra rat model of salt-susceptibility. In the genomic arm of
      the project, we previously detected in male rats two salt-susceptibility QTLs on
      chromosome 1, SS1a (D1Mgh2-D1Mit11; span 43.1 cM) and SS1b (D1Mit11-D1Mit4; span
      18 cM). In the transcriptomic arm, we studied differential gene expression in
      kidneys of SBH/y and SBN/y rats that had been fed regular diet or salt-loaded. We
      used the Affymetrix Rat Genome RAE230 GeneChip and probed >30,000 transcripts.
      The research algorithm called for an initial genome-wide screen for
      differentially expressed transcripts between the study groups. This step was
      followed by cluster analysis based on 2x2 ANOVA to identify transcripts that were
      of relevance specifically to salt-sensitivity and hypertension and to salt
      resistance. The two arms of the project were integrated by identifying those
      differentially expressed transcripts that showed an allele-specific hypertensive
      effect on salt-loading and that mapped within the defined boundaries of the salt
      susceptibility QTLs on chromosome 1. The differentially expressed transcripts
      were confirmed by RT-PCR. Of the 2933 genes annotated to rat chromosome 1, 1102
      genes were identified within the boundaries of the two blood pressure QTLs. The
      microarray identified 2470 transcripts that were differentially expressed between
      the study groups. Cluster analysis identified genome-wide 192 genes that were
      relevant to salt-susceptibility and/or hypertension, 19 of which mapped to
      chromosome 1. Eight of these genes mapped within the boundaries of QTLs SS1a and
      SS1b. RT-PCR confirmed 7 genes, leaving TcTex1, Myadm, Lisch7, Axl-like, Fah,
      PRC1-like, and Serpinh1. None of these genes has been implicated in hypertension
      before. These genes become henceforth targets for our continuing search for the
      genetic basis of hypertension.

PMID- 15731462
TI  - Autonomic control of cardiac action potentials: role of potassium channel
      kinetics in response to sympathetic stimulation.
AB  - I(Ks), the slowly activating component of the delayed rectifier current, plays a
      major role in repolarization of the cardiac action potential (AP). Genetic
      mutations in the alpha- (KCNQ1) and beta- (KCNE1) subunits of I(Ks) underlie Long
      QT Syndrome type 1 and 5 (LQT-1 and LQT-5), respectively, and predispose carriers
      to the development of polymorphic ventricular arrhythmias and sudden cardiac
      death. beta-adrenergic stimulation increases I(Ks) and results in rate dependent
      AP shortening, a control system that can be disrupted by some mutations linked to
      LQT-1 and LQT-5. The mechanisms by which I(Ks) regulates action potential
      duration (APD) during beta-adrenergic stimulation at different heart rates are
      not known, nor are the consequences of mutation induced disruption of this
      regulation. Here we develop a complementary experimental and theoretical approach
      to address these questions. We reconstituted I(Ks) in CHO cells (ie, KCNQ1
      coexpressed with KCNE1 and the adaptator protein Yotiao) and quantitatively
      examined the effects of beta-adrenergic stimulation on channel kinetics. We then
      developed theoretical models of I(Ks) in the absence and presence of beta
      adrenergic stimulation. We simulated the effects of sympathetic stimulation on
      channel activation (speeding) and deactivation (slowing) kinetics on the whole
      cell action potential under different pacing conditions. The model suggests these
      kinetic effects are critically important in rate-dependent control of action
      potential duration. We also investigate the effects of two LQT-5 mutations that
      alter kinetics and impair sympathetic stimulation of I(Ks) and show the likely
      mechanism by which they lead to tachyarrhythmias and indicate a distinct role of
      I(KS) kinetics in this electrical dysfunction. The full text of this article is
      available online at http://circres.ahajournals.org.

PMID- 15731463
TI  - Atherosclerotic abdominal aortic aneurysm and the interaction between autologous
      human plaque-derived vascular smooth muscle cells, type 1 NKT, and helper T
      cells.
AB  - Immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation, and
      apoptosis are pathological hallmarks of atherosclerosis. The multifocal, chronic,
      and inflammatory nature of this disease of the cardiovascular system complicates
      targeted cellular therapy and emphasizes the need to understand the role and
      interaction of immune cells with VSMCs. We characterized the immune cell subsets
      present in human atherosclerotic tissue derived from atherosclerotic abdominal
      aortic aneurysm (AAA) and expanded them to study their interaction with
      autologous plaque-derived VSMCs in vitro. We show here that apart from T
      lymphocytes, plaque infiltrates consist of lots of NK cells and significant
      proportions of NKT cells that express T cell receptor (TCR) alphabeta, CD4, and
      the NK markers CD56 and CD161. The infiltrates are predominantly IFN-gamma
      producing Type 1 lymphoid cells. When cocultured, the T and NKT cells adhere to
      VSMCs. CD4+ T cells enhance VSMC proliferation. VSMCs in turn enhance CD4+CD161+
      NKT but not CD4+ or CD8+ T cell proliferation. CD4+CD161+ NKT cells inhibit VSMC
      proliferation by inducing apoptosis. Our results suggest that the interactions of
      Type 1 CD4+ T and CD4+CD161+ NKT cells with VSMCs may regulate VSMC proliferation
      and death respectively in atherosclerosis and the balance of these interactions
      could determine plaque stability.

PMID- 15731464
TI  - Distinct NF-kappaB regulation by shear stress through Ras-dependent IkappaBalpha
      oscillations: real-time analysis of flow-mediated activation in live cells.
AB  - NF-kappaB, a transcription factor central to inflammatory regulation during
      development of atherosclerosis, is activated by soluble mediators and through
      biomechanical inputs such as flow-mediated shear- stress. To investigate the
      molecular mechanisms underlying shear stress mediated signal transduction in
      vascular cells we have developed a system that applies flow-mediated shear stress
      in a controlled manner, while inserted in a confocal microscope. In combination
      with GFP-based methods, this allows continuous monitoring of flow induced signal
      transduction in live cells and in real time. Flow-mediated shear stress, induced
      using the system, caused a successive increase in NF-kappaB-regulated gene
      activation. Experiments assessing the mechanisms underlying the NF-kappaB induced
      activity showed time and flow rate dependent effects on the inhibitor,
      IkappaBalpha, involving nuclear translocation characterized by a biphasic or
      cyclic pattern. The effect was observed in both endothelial- and smooth muscle
      cells, demonstrated to impact noncomplexed IkappaBalpha, and to involve
      mechanisms distinct from those mediating cytokine signals. In contrast, effects
      on the NF-kappaB subunit relA were similar to those observed during cytokine
      stimulation. Further experiments showed the flow induced inter-compartmental
      transport of IkappaBalpha to be regulated through the Ras GTP-ase, demonstrating
      a pronounced reduction in the effects following blocking of Ras activity. These
      studies show that flow-mediated shear stress, regulated by the Ras GTP-ase, uses
      distinct mechanisms of NF-kappaB control at the molecular level. The oscillatory
      pattern, reflecting inter-compartmental translocation of IkappaBetaalpha, is
      likely to have fundamental impact on pathway regulation and on development of
      shear stress-induced distinct vascular cell phenotypes.

PMID- 15731465
TI  - Incidence and short-term prognosis of transient ischemic attack in a population
      based study.
AB  - BACKGROUND AND PURPOSE: Transient ischemic attacks (TIAs) have been shown to be a
      strong predictor of subsequent stroke and death. We present the incidence and
      short-term prognosis of TIA within a large population with a significant
      proportion of minorities with out-of-hospital TIA. METHODS: TIA cases were
      identified between July 1, 1993 and June 30, 1994 from the Greater
      Cincinnati/Northern Kentucky population of 1.3 million inhabitants by previously
      published surveillance methods, including inpatient and out-of-hospital events.
      Incidence rates were adjusted to the 1990 population, and life-table analyses
      were used for prognosis. RESULTS: The overall race, age, and gender-adjusted
      incidence rate for TIA within our population was 83 per 100,000, with age, race,
      and gender adjusted to the 1990 US population. Blacks and men had significantly
      higher rates of TIA than whites and women. Risk of stroke after TIA was 14.6% at
      3 months, and risk of TIA/stroke/death was 25.2%. Age, race, and sex were not
      associated with recurrent TIA or subsequent stroke in our population, but age was
      associated with mortality. CONCLUSIONS: Using our incidence rates for TIA in
      blacks and whites, we conservatively estimate that approximately 240 000 TIAs
      occurred in 2002 in the United States. Our incidence rate of TIA is slightly
      higher than previously reported, which may be related to the inclusion of blacks
      and out-of-hospital events. There are racial and gender-related differences in
      the incidence of TIA. We found a striking risk of adverse events after TIA;
      however, there were no racial or gender differences predicting these events.
      Further study is warranted in interventions to prevent these adverse events after
      TIA.

PMID- 15731466
TI  - William M. Feinberg Lecture: Cognitive vitality and the role of stroke and
      cardiovascular disease risk factors.
AB  - BACKGROUND AND PURPOSE: Vascular risk factors are common in the elderly, and some
      such as hypertension may be important predictors of cognitive impairment. SUMMARY
      OF REVIEW: In this article, the role that vascular risk factors may play in the
      prevention of vascular and nonvascular forms of cognitive impairment is reviewed.
      CONCLUSIONS: Because vascular risk factors may have negative effects on brain
      structure and cognitive function, and because vascular risk factors may be
      present in midlife or possibly earlier, we may need to develop long-term
      intervention strategies to control or prevent vascular risk factors in an effort
      to preserve cognitive vitality as we age.

PMID- 15731473
TI  - Emergency administration of abciximab for treatment of patients with acute
      ischemic stroke: results of a randomized phase 2 trial.
AB  - BACKGROUND AND PURPOSE: Because of its success in treatment of acute cardiac
      ischemia, there is interest in the use of abciximab for treating patients with
      acute ischemic stroke. A previous dose-escalation study determined that abciximab
      could be given safely in a regimen of 0.25 mg/kg intravenous bolus followed by a
      12-hour infusion at 0.125 microg/kg per minute (maximum 10 microg/min). This
      study was performed to obtain more information about the safety and potential
      efficacy of abciximab in patients with stroke. METHODS: An international
      randomized, double-blind, placebo-controlled phase 2 trial enrolled 400 patients
      within 6 hours of onset of ischemic stroke. The primary safety outcome was the
      rate of symptomatic hemorrhage that occurred during the first 5 days after
      stroke. The primary efficacy measure was the distribution of outcomes at 3 months
      after stroke using the modified Rankin Scale (mRS) based on an ordinal regression
      model of outcomes, adjusting for baseline severity of stroke, age, and interval
      from stroke. RESULTS: Symptomatic intracranial hemorrhage within 5 days was
      diagnosed in 7 of 195 (3.6%) patients treated with abciximab and 2 of 199 (1%)
      patients given placebo (odds ratio [OR], 3.7; P=0.09; 95% confidence interval
      [CI], 0.7 to 25.9). Asymptomatic hemorrhagic transformation was detected by brain
      imaging in 24 patients administered abciximab and 33 patients receiving placebo
      (OR, 0.74; P=0.25; 95% CI, 0.4 to 1.3). Treatment with abciximab showed a
      nonsignificant shift in favorable outcomes as measured by mRS scores at 3 months
      (OR, 1.20; P=0.33; 95% CI, 0.84 to 1.70). CONCLUSIONS: Intravenously administered
      abciximab can be given to patients with a reasonable degree of safety. The trial
      also suggests that abciximab could improve outcomes at 3 months after stroke. A
      larger randomized, double-blind, placebo-controlled trial is necessary to test
      the efficacy of abciximab.

PMID- 15731474
TI  - NF-kappaB activation plays a role in superoxide-mediated cerebral endothelial
      dysfunction after hypoxia/reoxygenation.
AB  - BACKGROUND AND PURPOSE: Cerebral vascular injury occurs in response to
      hypoxia/reoxygenation (H/R). However, the cellular signaling pathways that
      regulate this event remain unclear. The present study was designed to determine
      whether reactive oxygen species (ROS) mediate endothelial dysfunction after H/R
      in cerebral resistance arteries and, if so, the relative contribution of ROS,
      NADPH oxidase, and a nuclear factor-kappaB (NF-kappaB) pathway. METHODS: Arterial
      diameter and intraluminal pressure were simultaneously measured on rat posterior
      cerebral arteries (PCA). Superoxide was measured by 5-micromol/L lucigenin
      enhanced chemiluminescence. RESULTS: Hypoxia/reoxygenation selectively inhibited
      cerebral vasodilation to the endothelium-dependent agonist acetylcholine (Ach)
      (0.01 to 10 micromol/L) by approximately 50%. Impaired vasodilation after H/R was
      reversed by 2,2,6,6-tetramethylpiperidine-N-oxyl (Tempo) (100 micromol/L), a cell
      permeable superoxide dismutase mimetic, and partially by ebselen (10 micromol/L),
      a peroxynitrite scavenger. H/R-impaired vasodilation to Ach was also preserved by
      apocynin (1 mmol/L), a specific inhibitor for NADPH oxidase. Correspondingly, H/R
      significantly increased lucigenin-detectable superoxide, which was reduced by
      either Tempo or apocynin, but not by allopurinol (10 micromol/L), an inhibitor of
      xanthine oxidase. Finally, the NF-kappaB inhibitors helenalin (10 micromol/L) and
      MG-132 (1 micromol/L) independently antagonized H/R-impaired Ach-induced
      vasodilation without affecting dilator response to sodium nitroprusside, an
      endothelium-independent vasodilator. CONCLUSIONS: These results indicate that
      superoxide mediates cerebral endothelial dysfunction after hypoxia/reoxygenation
      largely via activation of NADPH oxidase and possibly activation of NF-kappaB
      pathway.

PMID- 15731475
TI  - Is heparin treatment the optimal management for cerebral venous thrombosis?
      Effect of abciximab, recombinant tissue plasminogen activator, and enoxaparin in
      experimentally induced superior sagittal sinus thrombosis.
AB  - BACKGROUND: Based on a newly developed model of reversible superior sagittal
      sinus (SSS) thrombosis in the rat, we investigated the effect of thrombolytic and
      anticoagulant treatment on recanalization, brain parenchymal changes, and motor
      deficits. METHODS: Thrombosis of the SSS was induced by topical application of
      ferric chloride. Occlusion was confirmed by magnetic resonance angiography (MRA).
      Six hours after operation, single treatment with 10 mg recombinant tissue
      plasminogen activator (rtPA)/kg and 6 mg abciximab/kg or subcutaneous injection
      of 450 IU/kg enoxaparin twice daily was started, each group containing 10 rats.
      Follow-up MRI with T2- and diffusion-weighted images was performed on the first,
      second, and seventh postoperative day. RESULTS: Control and enoxaparin-treated
      animals developed diffuse brain edema without infarction or intracerebral
      bleeding. This was indicated by an increase of T2 relaxation time and a decrease
      of the apparent diffusion coefficient in the parasagittal and lateral cortex. In
      these groups, the degree of recanalization after 7 days was comparable (48%
      versus 52%). Enoxaparin-treated animals showed significant amelioration of
      functional deficits. Clinical outcome was best in the abciximab-treated group,
      with a residual sinus occlusion of 36% after 1 week. Highest recanalization was
      achieved by lysis with rtPA (85%). CONCLUSIONS: Enoxaparin treatment in rats with
      cerebral venous thrombosis significantly influences clinical outcome. However, it
      has no effect on recanalization. GPIIb/IIIa antagonists and rtPA accelerate
      thrombolysis. They may represent an alternative in treatment of cerebral venous
      thrombosis.

PMID- 15731476
TI  - Sex differences in stroke care and outcomes: results from the Registry of the
      Canadian Stroke Network.
AB  - BACKGROUND: Stroke is an important cause of death and disability in women as well
      as men. However, little is known about sex differences in stroke care and
      outcomes. METHODS: The Registry of the Canadian Stroke Network (RCSN) captured
      data on patients with stroke seen at acute care hospitals across Canada. We used
      data from phase 1 (July 2001 to February 2002) and phase 2 (June to December
      2002) of the RCSN to compare stroke presentation, management, and 6-month
      outcomes in women and men using multivariable regression techniques to adjust for
      age and other factors. RESULTS: The study sample included 3323 patients, with
      1527 women. Stroke symptoms at presentation were similar in women and men, except
      that women were more likely to present with headaches and were less likely to
      have brain stem or cerebellar symptoms. There were no sex differences in the use
      of neuroimaging, thrombolysis, antithrombotic therapy, or consultations. Women
      were less likely than men to receive care on an acute stroke unit, but this
      difference was no longer significant after adjustment for age and other factors.
      Women were more likely than men to be discharged to long-term care and had
      greater disability at 6 months. Mortality and quality of life at 6 months were
      similar in women and men. CONCLUSIONS: Among patients participating in the RCSN,
      there were no major sex differences in stroke presentation or management.
      Compared with men, women were more often institutionalized and had a slightly
      worse functional status at 6 months after stroke.

PMID- 15731477
TI  - Derivation of transcranial Doppler criteria for rescue intra-arterial
      thrombolysis: multicenter experience from the Interventional Management of Stroke
      study.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) has the potential to identify
      acute stroke patients with arterial occlusion when treatment with intravenous
      recombinant tissue plasminogen activator (rtPA) may fail to open the vessel. We
      examined clinical utility and prognostic value of TCD flow findings in patients
      enrolled in an intravenous/intra-arterial rtPA pilot trial (Interventional
      Management of Stroke [IMS] study). METHODS: Patients enrolled in the IMS trial
      who underwent urgent TCD performed before intra-arterial rtPA treatment were
      included. TCD findings were analyzed by a mean flow velocity (MFV) ratio using
      reciprocal middle carotid artery (MCA) depths bilaterally (affected MCA-to
      contralateral MCA MFV ratio [aMCA/cMCA MFV ratio]). The clinical utility of TCD
      was determined by its ability to predict outcome and identify a proximal arterial
      occlusion that requires intra-arterial lysis per protocol. RESULTS: Twenty-nine
      of 80 patients enrolled in IMS trial had pre-intra-arterial lysis TCD (mean age,
      61+/-11; men-to-women ratio: 17:12; median baseline National Institutes of Health
      Stroke Score, 17). No temporal window was found in 3 patients (10%). Cerebral
      angiography was performed at mean 174+/-36 minutes from stroke onset. TCD was
      performed at median 93.5 minutes from onset. The aMCA/cMCA MFV ratio <0.6 had a
      sensitivity of 94% (95% confidence interval [CI], 63% to 99%), specificity of
      100% (97.5%; lower CI of 54%), positive predictive value of 100% (lower CI, 80%);
      and negative predictive value of 86% (CI, 42% to 99%) for identifying proximal
      occlusion in the anterior circulation that require intra-arterial lysis. All
      patients with absent MCA flow (n=6) had poor outcomes (modified Rankin Scale > or
      =3) (P=0.014). CONCLUSIONS: TCD is a useful modality for evaluating the arterial
      circulation in acute ischemic stroke patients; it may have significant potential
      as a screening tool for intravenous/intra-arterial lysis protocols.

PMID- 15731478
TI  - A simple 3-item stroke scale: comparison with the National Institutes of Health
      Stroke Scale and prediction of middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: The purpose of the study was to design a simple stroke
      scale that requires minimal training but reflects initial stroke severity and is
      predictive of middle cerebral artery (MCA) occlusion. METHODS: The new stroke
      scale assessed 3 parameters: (1) level of consciousness, (2) gaze, and (3) motor
      function. Each item was graded 0 to 2, where 0 indicated normal findings and 2
      severe abnormalities (ie, profound drowsiness or worse, forced gaze deviation,
      and severe hemiparesis, respectively). During a study period of 11 months,
      patients presenting with acute stroke symptoms (onset < or =6 hours) were
      examined by a stroke neurologist assessing the new scale as well as the National
      Institutes of Health Stroke Scale (NIHSS). In addition, 83 patients received
      acute magnetic resonance angiography (MRA; as part of an acute stroke protocol).
      RESULTS: The new stroke scale was strongly associated with the NIHSS.
      Interobserver reliability of the new scale was high (intraclass correlation
      coefficient 0.947). Using post hoc analysis, a score of > or =4 predicted
      proximal vessel occlusion (T-segment or M1-segment occlusion of the MCA on MRA)
      almost as accurately (overall accuracy 0.86) as an NIHSS score of >or =14
      (overall accuracy 0.93). CONCLUSIONS: The new stroke scale reflects acute stroke
      severity well and predicts proximal MCA occlusion with reasonable accuracy.
      However, the clinical scale needs further evaluation before it can be recommended
      as a tool for the triage of acute stroke patients.

PMID- 15731479
TI  - ALOX5AP gene and the PDE4D gene in a central European population of stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Recent evidence has implicated the genes for 5
      lipoxygenase activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) as
      susceptibility genes for stroke in the Icelandic population. The aim of the
      present study was to explore the role of these genes in a central European
      population of stroke patients. METHODS: A total of 639 consecutive stroke
      patients and 736 unrelated population-based controls that had been matched for
      age and sex were examined using a case-control design. Twenty-two single
      nucleotide polymorphisms (SNPs) covering ALOX5AP were genotyped. For PDE4D,
      microsatellite AC008818-1 and 12 SNPs, which tag all common haplotypes in
      previously identified linkage disequilibrium (LD) blocks, were analyzed. RESULTS:
      A nominally significant association with stroke was observed with several SNPs
      from ALOX5AP, including SNP SG13S114, which had been part of the Icelandic at
      risk haplotype. Associations were stronger in males than in females, with
      SG13S114 (odds ratio, 1.24; 95% CI, 1.04 to 1.55; P=0.017) and SG13S100 (odds
      ratio, 1.26; 95% CI 1.03 to 1.54; P=0.024) showing the strongest associations. No
      significant associations were detected with single markers and haplotypes in
      PDE4D. The frequencies of single-marker alleles and haplotypes differed largely
      from those in the Icelandic population. CONCLUSIONS: The present study suggests
      that sequence variants in the ALOX5AP gene are significantly associated with
      stroke, particularly in males. Variants in the PDE4D gene are not a major risk
      factor for stroke in individuals from central Europe. Population differences in
      allele and haplotype frequencies as well as LD structure may contribute to the
      observed differences between populations.

PMID- 15731480
TI  - Adiponectin and coronary heart disease: the Strong Heart Study.

PMID- 15731481
TI  - Dyslipidemia and thrombosis: causal relationship or epiphenomenon of sedentary
      lifestyle?

PMID- 15731482
TI  - Fitness versus fatness: the debate continues.

PMID- 15731483
TI  - Recommendations for blood pressure measurement in humans and experimental
      animals: part 2: blood pressure measurement in experimental animals: a statement
      for professionals from the Subcommittee of Professional and Public Education of
      the American Heart Association Council on High Blood Pressure Research.
AB  - In experimental animals, as in humans, techniques for measuring blood pressure
      (BP) have improved considerably over the past decade. In this document, we
      present recommendations for measuring BP in experimental animals with the goal of
      helping investigators select optimal methods for BP monitoring in the research
      laboratory. The advantages and disadvantages of various BP measurement methods
      are discussed and specific recommendations are provided for selecting the optimal
      technique depending on the study objective. Although indirect techniques that
      permit only sporadic measurements of BP may be suitable for some purposes,
      methods for directly measuring BP are generally preferred because of their
      ability to monitor the highly dynamic nature of BP in a comprehensive fashion.
      Selection of the methods to be used should ultimately be guided by the study
      objectives to insure that the techniques chosen are appropriate for the
      experimental questions being explored.

PMID- 15731485
TI  - Increased ApoB in small dense LDL particles predicts premature coronary artery
      disease.

PMID- 15731486
TI  - Aortic stenosis and statins: more evidence of "pleotropy"?

PMID- 15731487
TI  - Recommendations for blood pressure measurement in animals: summary of an AHA
      scientific statement from the Council on High Blood Pressure Research,
      Professional and Public Education Subcommittee.

PMID- 15731488
TI  - Novel approaches to the treatment of dyslipidemia.

PMID- 15731489
TI  - Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a
      case-control study.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with
      obesity, diabetes, and dyslipidemia. We examined whether NAFLD was associated
      with atherosclerosis, as measured by ultrasound in the carotid arteries. METHODS
      AND RESULTS: Carotid atherosclerosis and cardiovascular risk factors were
      assessed in 40 patients with an ultrasound diagnosis of primary NAFLD and 40
      matched population controls. The metabolic syndrome and all its individual
      traits, including elevated C-reactive protein, were significantly (P<0.005) more
      frequent in NAFLD patients than in control subjects. Patients with NAFLD showed
      more carotid atherosclerosis than controls, with mean intima-media thickness
      (IMT) of 0.70+/-0.20 mm and 0.54+/-0.13 mm (P<0.0001) and plaque prevalence of
      50% and 25% (P=0.021), respectively. By multivariate analysis, older age (odds
      ratio [OR], 2.5 per 10 years; 95% CI, 1.4 to 4.4; P=0.002), the presence of NAFLD
      (OR, 8.4; 95% CI, 2.49 to 29.4; P=0.001), and elevated serum ferritin (OR, 3.1;
      95% CI, 1.2 to 7.9; P=0.016) were independent predictors of an increased IMT.
      CONCLUSIONS: Patients with NAFLD show a cluster of risk factors of the metabolic
      syndrome and advanced carotid atherosclerosis. NAFLD appears to be a feature of
      the metabolic syndrome, and its detection on abdominal ultrasound should alert to
      the existence of an increased cardiovascular risk.

PMID- 15731490
TI  - Role of insulin resistance in familial combined hyperlipidemia.
AB  - OBJECTIVE: Insulin resistance is associated with increased triglyceride levels,
      low high-density lipoprotein cholesterol, small dense low-density lipoprotein
      (LDL), and increased apolipoprotein B (apoB) levels, all characteristics of
      familial combined hyperlipidemia (FCH). Therefore, we explored the role of
      insulin resistance in FCH lipid phenotype expression. METHODS AND RESULTS: FCH
      was defined by traditional diagnostic criteria including plasma total cholesterol
      or triglyceride levels >90th percentile. Insulin resistance was assessed by the
      Homeostasis Model Assessment (HOMA) index. In total, 132 subjects with FCH, 350
      normolipidemic relatives, and 81 spouses who referenced as controls were studied.
      FCH subjects were significantly more insulin resistant compared with controls and
      normolipidemic relatives (HOMA index 2.9 [95% CI, 2.6 to 3.2], 2.2 [95% CI, 2.0
      to 2.5], and 2.0 [95% CI, 1.9 to 2.2], respectively), even after correction for
      sex, age, and body mass index (BMI). The degree of insulin resistance was
      associated with the lipid phenotype expression, and a change in insulin-resistant
      state was associated with a change in lipid phenotype expression over 5 years.
      For any level of insulin resistance and degree of obesity, FCH subjects had
      increased levels of apoB and more small dense LDL compared with controls.
      CONCLUSIONS: Insulin resistance is a characteristic feature of FCH, which is not
      fully explained by their increased BMI and is associated with (change in) lipid
      phenotype expression. Furthermore, our results support the concept of genetic
      origin of high apoB and small dense LDL in FCH, which is modulated by insulin
      resistance and obesity.

PMID- 15731491
TI  - Role of Gas-6 in adipogenesis and nutritionally induced adipose tissue
      development in mice.
AB  - OBJECTIVE: A potential role of growth arrest-specific gene 6 (Gas-6) in energy
      storage in adipose tissue was investigated in murine models of obesity. Gas-6 is
      a ligand for the Axl, C-Mer, and Sky family of tyrosine kinase receptors. METHODS
      AND RESULTS: Whereas Gas-6, C-Mer, and Sky were expressed in mature murine
      adipocytes, the expression of Axl was restricted to the stromal-vascular
      fraction, which includes pre-adipocytes. During the in vitro conversion of
      adipogenic 3T3-F442A cells into mature adipocytes, the expression of Gas-6
      increased in undifferentiated confluent pre-adipocytes during a transient phase
      of growth arrest. On treatment of these cells with an adipogenic medium, Gas-6
      expression decreased sharply, coinciding with expression of early adipocytes
      markers. This modulation was not observed in the nonadipogenic 3T3-C2 cells. The
      Gas-6 mRNA level was transiently downregulated during nutritionally induced
      expansion of adipose tissues in vivo. When kept on a standard diet, no
      significant difference in either total body weight or weight of gonadal or
      subcutaneous fat pads was observed between Gas-6 deficient and wild-type mice. On
      exposure to a high-fat diet, however, Gas-6-deficient mice had significantly less
      fat mass than their wild-type counterparts. CONCLUSIONS: Gas-6 enhances the
      accumulation of adipose tissue in diet-induced obese mice.

PMID- 15731492
TI  - Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology,
      epidemiology, and possible therapeutic target.
AB  - The development of atherosclerotic vascular disease is invariably linked to the
      formation of bioactive lipid mediators and accompanying vascular inflammation.
      Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that is produced
      by inflammatory cells, co-travels with circulating low-density lipoprotein (LDL),
      and hydrolyzes oxidized phospholipids in LDL. Its biological role has been
      controversial with initial reports purporting atheroprotective effects of Lp-PLA2
      thought to be a consequence of degrading platelet-activating factor and removing
      polar phospholipids in modified LDL. Recent studies, however, focused on pro
      inflammatory role of Lp-PLA2 mediated by products of the Lp-PLA2 reaction
      (lysophosphatidylcholine and oxidized nonesterified fatty acids). These bioactive
      lipid mediators, which are generated in lesion-prone vasculature and to a lesser
      extent in the circulation (eg, in electronegative LDL), are known to elicit
      several inflammatory responses. The proinflammatory action of Lp-PLA2 is also
      supported by a number of epidemiology studies suggesting that the circulating
      level of the enzyme is an independent predictor of cardiovascular events, despite
      some attenuation of the effect by inclusion of LDL, the primary carrier of Lp
      PLA2, in the analysis. These observations provide a rationale to explore whether
      inhibiting Lp-PLA2 activity and consequent interference with the formation of
      bioactive lipid mediators will abrogate inflammation associated with
      atherosclerosis, produce favorable changes in intermediate cardiovascular end
      points (eg, biomarkers, imaging, and endothelial function), and ultimately reduce
      cardiovascular events in high-risk patients.

PMID- 15731493
TI  - Free fatty acid impairment of nitric oxide production in endothelial cells is
      mediated by IKKbeta.
AB  - OBJECTIVE: Free fatty acids (FFA) are commonly elevated in diabetes and obesity
      and have been shown to impair nitric oxide (NO) production by endothelial cells.
      However, the signaling pathways responsible for FFA impairment of NO production
      in endothelial cells have not been characterized. Insulin receptor substrate-1
      (IRS-1) regulation is critical for activation of endothelial nitric oxide
      synthase (eNOS) in response to stimulation by insulin or fluid shear stress.
      METHODS AND RESULTS: We demonstrate that insulin-mediated tyrosine
      phosphorylation of IRS-1 and serine phosphorylation of Akt, eNOS, and NO
      production are significantly inhibited by treatment of bovine aortic endothelial
      cells with 100 micromol/L FFA composed of palmitic acid for 3 hours before
      stimulation with 100 nM insulin. This FFA preparation also increases, in a dose
      dependent manner, IKKbeta activity, which regulates activation of NF- kappaB, a
      transcriptional factor associated with inflammation. Similarly, elevation of
      other common FFA such as oleic and linoleic acid also induce IKKbeta activation
      and inhibit insulin-mediated eNOS activation. Overexpression of a kinase inactive
      form of IKKbeta blocks the ability of FFA to inhibit insulin-dependent NO
      production, whereas overexpression of wild-type IKKbeta recapitulates the effect
      of FFA on insulin-dependent NO production. CONCLUSIONS: Elevated levels of common
      FFA found in human serum activate IKKbeta in endothelial cells leading to reduced
      NO production, and thus may serve to link pathways involved in inflammation and
      endothelial dysfunction.

PMID- 15731494
TI  - Mechanisms, pathophysiology, and therapy of arterial stiffness.
AB  - Arterial stiffness is a growing epidemic associated with increased risk of
      cardiovascular events, dementia, and death. Decreased compliance of the central
      vasculature alters arterial pressure and flow dynamics and impacts cardiac
      performance and coronary perfusion. This article reviews the structural,
      cellular, and genetic contributors to arterial stiffness, including the roles of
      the scaffolding proteins, extracellular matrix, inflammatory molecules,
      endothelial cell function, and reactive oxidant species. Additional influences of
      atherosclerosis, glucose regulation, chronic renal disease, salt, and changes in
      neurohormonal regulation are discussed. A review of the hemodynamic impact of
      arterial stiffness follows. A number of lifestyle changes and therapies that
      reduce arterial stiffness are presented, including weight loss, exercise, salt
      reduction, alcohol consumption, and neuroendocrine-directed therapies, such as
      those targeting the renin-angiotensin aldosterone system, natriuretic peptides,
      insulin modulators, as well as novel therapies that target advanced glycation end
      products.

PMID- 15731495
TI  - Association of C-reactive protein with blood pressure and hypertension: life
      course confounding and mendelian randomization tests of causality.
AB  - BACKGROUND: C-reactive protein (CRP) has repeatedly been associated with blood
      pressure and prevalent and incident hypertension, but whether a causal link
      exists is uncertain. METHODS AND RESULTS: We assessed the cross-sectional
      relations of CRP to systolic blood pressure, pulse pressure, and prevalent
      hypertension in a representative sample of >3500 British women aged 60 to 79
      years. For both outcomes, substantial associations were observed. However, these
      associations were greatly attenuated by adjustment for a wide range of
      confounding factors acting over the life course. We further investigated
      causality using a Mendelian randomization approach by examining the association
      of the 1059G/C polymorphism in the human CRP gene with CRP and with blood
      pressure, pulse pressure, and hypertension. The polymorphism was associated with
      a robust difference in CRP, and the expectation would be for higher blood
      pressure and pulse pressure and greater prevalence of hypertension among those
      carrying the genetic variant associated with higher CRP levels. This was not
      observed, and the predicted causal effects of CRP on blood pressure, pulse
      pressure, and hypertension using instrumental variables methods were close to 0,
      although with wide CIs. CONCLUSIONS: CRP levels are associated with blood
      pressure, pulse pressure, and hypertension, but adjustment for life course
      confounding and a Mendelian randomization approach suggest the elevated CRP
      levels do not lead to elevated blood pressure.

PMID- 15731496
TI  - Plasma levels of soluble receptor for advanced glycation end products and
      coronary artery disease in nondiabetic men.
AB  - OBJECTIVE: The receptor for advanced glycation end products (RAGE) is a cell
      surface receptor whose signaling pathway has been implicated in atherogenesis.
      RAGE has an endogenous secretory receptor form, called soluble RAGE (sRAGE), that
      could exert antiatherogenic effects by acting as a decoy. We sought to determine
      whether a decreased plasma level of sRAGE could be independently associated with
      the prevalence of coronary artery disease (CAD) in nondiabetic men. METHODS AND
      RESULTS: Plasma levels of sRAGE were determined in 328 nondiabetic male patients
      with angiographically proved CAD and in 328 age-matched healthy controls. The
      concentration of sRAGE in plasma was significantly lower (P<0.0001) in CAD cases
      [median (interquartile range): 966 (658-1372) pg/mL] than in control subjects
      [1335 (936-1954) pg/mL]. In logistic regression analysis, the multivariate
      adjusted odds ratio for the presence of CAD was 6.719 (95% confidence interval,
      3.773 to 11.964; P<0.0001) when the lowest quartile of the sRAGE level was
      compared with the highest quartile. CONCLUSIONS: Our findings indicate that low
      levels of sRAGE in plasma are independently associated with the presence of CAD
      in nondiabetic men and suggest that sRAGE is one of the clinically important
      molecules associated with atherosclerosis.

PMID- 15731498
TI  - Preserving and promoting our discipline: pharmacology students speak out.

PMID- 15731497
TI  - Nuclear factor kappaB signaling in atherogenesis.
AB  - Atherosclerosis is an inflammatory disease, characterized by the accumulation of
      macrophage-derived foam cells in the vessel wall and accompanied by the
      production of a wide range of chemokines, cytokines, and growth factors. These
      factors regulate the turnover and differentiation of immigrating and resident
      cells, eventually influencing plaque development. One of the key regulators of
      inflammation is the transcription factor nuclear factor kappaB (NF-kappaB),
      which, for a long time, has been regarded as a proatherogenic factor, mainly
      because of its regulation of many of the proinflammatory genes linked to
      atherosclerosis. NF-kappaB may play an important role in guarding the delicate
      balance of the atherosclerotic process as a direct regulator of proinflammatory
      and anti-inflammatory genes and as a regulator of cell survival and
      proliferation. Here we address recent literature on the function of NF-kappaB in
      inflammatory responses and its relation to atherosclerosis.

PMID- 15731499
TI  - The ileocyte basolateral organic solute transporter (OSTalpha-OSTbeta) complex:
      finding the missing link in enterohepatic circulation.
AB  - Many drugs are removed from the body through a multistep process that includes
      covalent conjugation, transport into the bile, and excretion. Bile acids are
      transported across the ileocyte apical (brush border) membrane by the apical
      sodium-dependent bile-acid transporter (Asbt), but the identity of the primary
      transporter responsible for moving bile acids across the basolateral membrane of
      the ileocyte has remained a mystery, although not for a lack of protein
      pretenders to the throne. Recent insights from transcriptional profiling studies
      of wild-type and Asbt-deficient mice indicate that a complex formed by the
      organic solute carrier proteins alpha and beta (Ostalpha and Ostbeta) is the
      primary transporter for basolateral bile acid transport.

PMID- 15731500
TI  - Mast cells: the missing source of cardiac renin?
AB  - The renin-angiotensin system (RAS) acts to regulate blood volume and arterial
      pressure, and has direct effects on the heart. Renin, released by the kidney,
      circulates and acts-in the rate-limiting step of angiotensin II (Ang II)
      production-to convert angiotensinogen to inactive angiotensin I (Ang I). Ang II
      constricts vessels, leading to increased arterial pressure, among other effects.
      Components of the RAS have been found in a number of extra-renal tissues. Recent
      research indicates that mast cells in the heart may produce renin, creating a
      cardiac-specific RAS that acts locally to produce Ang II. These results, however,
      are not without controversy. Others have searched for sites of renin production
      and have found no other significant source that was physiologically important or
      that could not be completely ruled out as a possible contaminant. How important
      is mast cell-synthesized renin for direct cardiac-related effects?

PMID- 15731501
TI  - Molecular targeting in radiotherapy: epidermal growth factor receptor.
AB  - Radiation therapy is utilized as a treatment to cure or manage cancer; however,
      because of risk to local healthy tissue-and a modest success rate of some
      radiotherapy-strategies have been sought that would increase the therapeutic
      index of the treatment while reducing damage to surrounding tissue. Cell and
      tissue irradiation stimulates a series of biochemical and molecular signals;
      various components of this ionizing radiation (IR)-inducible signal transduction
      cascade can promote the survival of tumor cells. Identification of interactions
      between IR and a signaling pathway creates an opportunity to target those
      signaling intermediates to improve the outcome of radiotherapy. The epidermal
      growth factor receptor (EGFR, also termed ErbB1) is involved in normal
      development and differentiation of epithelial cells as well as in tumorigenesis.
      The EGFR is activated by IR, thus making this receptor and other members of the
      ErbB family important targets for radiosensitizing molecular interventions.
      Recent approaches have utilized monoclonal antibodies, small molecules, and
      transgenic technologies to undermine the kinase activity of EGFR.

PMID- 15731502
TI  - The economics of drug abuse: a quantitative assessment of drug demand.
AB  - Behavioral economic concepts have proven useful for an overall understanding of
      the regulation of behavior by environmental commodities and complements a
      pharmacological perspective on drug abuse in several ways. First, a quantitative
      assessment of drug demand, equated in terms of drug potency, allows meaningful
      comparisons to be made among drug reinforcers within and across pharmacological
      classes. Second, behavioral economics provides a conceptual framework for
      understanding key factors, both pharmacological and environmental, that
      contribute to reductions in consumption of illicit drugs. Finally, behavioral
      economics provides a basis for generalization from laboratory and clinical
      studies to the development of novel behavioral and pharmacological therapies.

PMID- 15731503
TI  - Neuropeptide S: a new player in the modulation of arousal and anxiety.
AB  - Neuropeptide S (NPS) is a newly identified transmitter that modulates arousal and
      fear responses. NPS activates an orphan G protein-coupled receptor that is
      expressed throughout the central nervous system, including brain centers that
      regulate sleep/wakefulness and anxiety. In contrast, the NPS precursor mRNA is
      found only in a few discrete nuclei in the brainstem as well as in a few
      scattered cells in the hypothalamus and amygdala. The most prominent expression
      of NPS precursor is found in a previously uncharacterized cluster of neurons in
      the pontine area, located between the noradrenergic locus ceruleus and
      Barrington's nucleus. Central administration of NPS induces long-lasting arousal
      and suppresses all stages of sleep. In addition, NPS produces an anxiolytic
      profile in a variety of behavioral models. The unique pharmacological spectrum of
      NPS makes it an interesting target for pharmaceutical development. It also
      enhances our understanding of the neurobiological mechanisms of sleep/wakefulness
      regulation and the neuronal processing of stress.

PMID- 15731505
TI  - Expression and regulation of small proline-rich protein 2 in allergic
      inflammation.
AB  - Asthma is a complex inflammatory pulmonary disorder that is on the rise despite
      intense ongoing research. We aimed to elucidate novel pathways involved in the
      pathogenesis of asthma. Employing asthma models induced by different allergens
      (ovalbumin and Aspergillus fumigatus), we uncovered the involvement of two
      members of the small proline-rich protein (SPRR) family, SPRR2a and SPRR2b, known
      to be involved in epithelial differentiation but not allergic disease. In situ
      hybridization revealed induction of SPRR2 signal in a subset of bronchial
      epithelial cells and mononuclear cells associated with inflammation after
      allergen challenge. Allergen-induced SPRR2 mRNA accumulation in the lung occurred
      in a time-dependent manner, with peak expression 10-96 h after a second ovalbumin
      challenge. Transgenic overexpression of interleukin (IL)-13 in the lungs resulted
      in a marked increase of SPRR2 expression, and allergen-induced SPRR2 expression
      was significantly decreased in IL-13-deficient mice. Studies in gene-targeted
      mice revealed that allergen-induced SPRR2 was dependent upon STAT6. Finally, we
      aimed to determine if the induction of SPRR2 by allergen was tissue specific.
      Notably, SPRR2 was markedly increased in the small intestine after induction of
      allergic gastrointestinal inflammation. Thus, SPRR2 is an allergen- and IL-13
      induced gene in experimental allergic responses that may be involved in disease
      pathophysiology.

PMID- 15731507
TI  - Intestinal responsiveness to experimental colitis in young rats is altered by
      maternal diet.
AB  - Increasing evidence suggests that fetal and neonatal nutrition impacts later
      health. Aims of the present study were to determine the effect of maternal
      dietary fat composition on intestinal phospholipid fatty acids and responsiveness
      to experimental colitis in suckling rat pups. Female rats were fed isocaloric
      diets varying only in fat composition throughout gestation and lactation. The
      oils used were high (8%) in n-3 [canola oil (18:3n-3)], n-6 (72%) [safflower oil
      (18:2n-6)], or n-9 (78%) [high oleic acid safflower oil (18:1n-9)] fatty acids, n
      = 6/group. Colitis was induced on postnatal day 15 by intrarectal 2,4
      dinitrobenzene sulfonic acid (DNBS) administration with vehicle (50% ethanol) and
      procedure (0.9% saline) controls. Jejunal and colonic phospholipids and milk
      fatty acids were determined. The distal colon was assessed for macroscopic
      damage, histology, and MPO activity. The 18:2n-6 maternal diet increased n-6
      fatty acids, whereas the 18:3n-3 diet increased n-3 fatty acids in milk and pup
      jejunal and colonic phospholipids. Maternal diet, milk, and pup intestinal n-6-to
      n-3 fatty acid ratios increased significantly in order: high 18:3n-3 < high 18:1n
      9 < high 18:2n-6. DNBS administration in pups in the high 18:2n-6 group led to
      severe colitis with higher colonic damage scores and MPO activity than in the
      18:1n-9 and 18:3n-3 groups. High maternal dietary 18:3n-3 intake was associated
      with colonic damage scores and MPO activity, which were not significantly
      different from ethanol controls. We demonstrate that maternal dietary fat
      influences the composition of intestinal lipids and responsiveness to
      experimental colitis in nursing offspring.

PMID- 15731506
TI  - Subcloning, localization, and expression of the rat intestinal sodium-hydrogen
      exchanger isoform 8.
AB  - Apically expressed intestinal and renal sodium-hydrogen exchangers (NHEs) play a
      major role in Na(+) absorption. Our previous studies on NHE ontogeny have shown
      that NHE-2 and NHE-3 are expressed at very low levels in young animals.
      Furthermore, single and/or double NHE-2 and NHE-3 knockout mice display no
      obvious abnormalities before weaning. These observations suggest that other
      transporter(s) may be involved in intestinal Na+ absorption during early life.
      The present studies were designed to clone the novel rat intestinal NHE-8 cDNA
      and to decipher the NHE-8 protein localization and gene expression pattern during
      different developmental stages. The rat NHE-8 cDNA has 2,160 bp and encodes a 575
      amino acid protein. An antibody against NHE-8 protein was developed.
      Immunohistochemistry staining indicated apical localization of NHE-8 protein in
      rat intestinal epithelial cells. The apical localization of NHE-8 was also
      confirmed by its presence in brush-border membrane and its absence in basolateral
      membrane preparations. Northern blotting utilizing a NHE-8-specific probe
      demonstrated higher NHE-8 mRNA expression in young animals compared with adult
      animals. Western blot analysis revealed a similar pattern. Tissue distribution
      with multiple human tissue RNA blot showed that NHE-8 was expressed in multiple
      tissues including the gastrointestinal tract. In conclusion, we have cloned the
      full-length NHE-8 cDNA from rat intestine and further showed its apical
      localization in intestinal epithelial cells. We have also shown that NHE-8 gene
      expression and protein expression were regulated during ontogeny. Our data
      suggests that NHE-8 may play an important role in intestinal Na+ absorption
      during early life.

PMID- 15731508
TI  - Meta-analysis: a case study.
AB  - This article raises some questions about the usefulness of meta-analysis as a
      means of reviewing quantitative research in the social sciences. When a meta
      analytic model for SAT coaching is used to predict results from future studies,
      the amount of prediction error is quite large. Interpretations of meta-analytic
      regressions and quantifications of program and study characteristics are shown to
      be equivocal. The match between the assumptions of the meta-analytic model and
      the data from SAT coaching studies is not good, making statistical inferences
      problematic. Researcher subjectivity is no less problematic in the context of a
      meta-analysis than in a narrative review.

PMID- 15731509
TI  - Evaluation of the effects of the Aban Aya Youth Project in reducing violence
      among African American adolescent males using latent class growth mixture
      modeling techniques.
AB  - This study employs growth mixture modeling techniques to evaluate the preventive
      effects of the Aban Aya Youth Project in reducing the rate of growth of violence
      among African American adolescent males (N = 552). Results suggest three distinct
      classes of participants: high risk (34%), medium risk (54%), and low risk (12%)
      based on both the participants' initial violence scores and their growth of
      violence over time. Results further show significant effects (almost 3 times as
      large as the effect found in the regular one-class analysis) for the high-risk
      class but not for the medium- or low-risk classes.

PMID- 15731510
TI  - Medical students' and tutors' experiences of directed and self-directed learning
      programs in evidence-based medicine: a qualitative evaluation accompanying a
      randomized controlled trial.
AB  - This qualitative study aims to interpret the results of a randomized controlled
      trial comparing two educational programs (directed learning and self-directed
      learning) in evidence-based medicine (EBM) for medical students at the University
      of Oslo from 2002 to 2003. There is currently very little comparative educational
      research in this field. In the trial, no statistically significant differences
      between the study groups were shown for any outcomes considered (EBM knowledge,
      skills, and attitudes). Further analysis suggests that main reason for the
      negative trial results was that the majority of students learned equally
      effectively, whichever program they received, although implementation of the
      educational programs was not complete because of varying attendance. This study
      illustrates a stepwise evaluation model that might be useful in evaluating other
      socially complex interventions.

PMID- 15731511
TI  - Using cluster analysis in program evaluation.
AB  - The conventional way to measure program impacts is to compute the average
      treatment effect; that is, the difference between a treatment group that received
      some intervention and a control group that did not. Recently, scholars have
      recognized that looking only at the average treatment effect may obscure impacts
      that accrue to subgroups. In an effort to inform subgroup analysis research, this
      article explains the challenge of treatment group heterogeneity. It then proposes
      using cluster analysis to identify otherwise difficult-to-identify subgroups
      within evaluation data. The approach maintains the integrity of the experimental
      evaluation design, thereby producing unbiased estimates of program impacts by
      subgroup. This method is applied to data from the evaluation of New York State's
      Child Assistance Program, a reform that intended to increase work and earnings
      among welfare recipients. The article interprets the substantive findings and
      then addresses the advantages and disadvantages of the proposed method.

PMID- 15731512
TI  - The 2005 Thomas Hunt Morgan Medal. Robert L. Metzenberg.

PMID- 15731513
TI  - The 2005 Genetics Society of America Medal. Steven J. Elledge.

PMID- 15731514
TI  - The 2005 George W. Beadle Medal. Thomas C. Kaufman.

PMID- 15731515
TI  - The favorable features of tryptophan synthase for proving Beadle and Tatum's one
      gene-one enzyme hypothesis.

PMID- 15731516
TI  - Successful implementation of genetic Education for Native Americans workshops at
      national conferences.
AB  - Genetic Education for Native Americans (GENA) was a National Human Genome
      Research Institute (NHGRI)/Ethical, Legal, and Social Implications (ELSI)-funded
      educational intervention designed to provide a unique genetics education program
      for Native American college and university students. A curriculum was developed
      and implemented in workshops in geographically diverse settings throughout the
      United States, primarily in conjunction with regional and national scientific
      conferences that include substantial numbers of Native American attendees. The
      original curriculum includes 24 objectives and has been offered in two formats,
      as a 16-hr "comprehensive" program and in briefer workshops (referred to as
      "customized" hereafter) that are designed to include objectives for selected
      audiences. Both formats teach sufficient genetics to allow discussion and
      understanding of the ELSI and cultural issues related to genetics science. This
      article describes the evaluation findings from our implementation of both formats
      of the GENA curriculum.

PMID- 15731517
TI  - Identification of a novel point mutation of mouse proto-oncogene c-kit through N
      ethyl-N-nitrosourea mutagenesis.
AB  - Manipulation of the mouse genome has emerged as an important approach for
      studying gene function and establishing human disease models. In this study, the
      mouse mutants were generated through N-ethyl-N-nitrosourea (ENU)-induced
      mutagenesis in C57BL/6J mice. The screening for dominant mutations yielded
      several mice with fur color abnormalities. One of them causes a phenotype similar
      to that shown by dominant-white spotting (W) allele mutants. This strain was
      named Wads because the homozygous mutant mice are white color, anemic, deaf, and
      sterile. The new mutation was mapped to 42 cM on chromosome five, where proto
      oncogene c-kit resides. Sequence analysis of c-kit cDNA from Wads(m/m) revealed a
      unique T-to-C transition mutation that resulted in Phe-to-Ser substitution at
      amino acid 856 within a highly conserved tyrosine kinase domain. Compared with
      other c-kit mutants, Wads may present a novel loss-of-function or hypomorphic
      mutation. In addition to the examination of adult phenotypes in hearing loss,
      anemia, and mast cell deficiency, we also detected some early developmental
      defects during germ cell differentiation in the testis and ovary of neonatal
      Wads(m/m) mice. Therefore, the Wads mutant may serve as a new disease model of
      human piebaldism, anemia, deafness, sterility, and mast cell diseases.

PMID- 15731519
TI  - An expectation-maximization-likelihood-ratio test for handling missing data:
      application in experimental crosses.
AB  - The mapping of quantitative trait loci (QTL) is an important research question in
      animal and human studies. Missing data are common in such study settings, and
      ignoring such missing data may result in biased estimates of the genotypic effect
      and thus may eventually lead to errant results and incorrect inferences. In this
      article, we developed an expectation-maximization (EM)-likelihood-ratio test
      (LRT) in QTL mapping. Simulation studies based on two different types of
      phylogenetic models revealed that the EM-LRT, a statistical technique that uses
      EM-based parameter estimates in the presence of missing data, offers a greater
      statistical power compared with the ordinary analysis-of-variance (ANOVA)-based
      test, which discards incomplete data. We applied both the EM-LRT and the ANOVA
      based test in a real data set collected from F2 intercross studies of inbred
      mouse strains. It was found that the EM-LRT makes an optimal use of the observed
      data and its advantages over the ANOVA F-test are more pronounced when more
      missing data are present. The EM-LRT method may have important implications in
      QTL mapping in experimental crosses.

PMID- 15731518
TI  - Effect of teosinte cytoplasmic genomes on maize phenotype.
AB  - Determining the contribution of organelle genes to plant phenotype is hampered by
      several factors, including the paucity of variation in the plastid and
      mitochondrial genomes. To circumvent this problem, evolutionary divergence
      between maize (Zea mays ssp. mays) and the teosintes, its closest relatives, was
      utilized as a source of cytoplasmic genetic variation. Maize lines in which the
      maize organelle genomes were replaced through serial backcrossing by those
      representing the entire genus, yielding alloplasmic sublines, or cytolines were
      created. To avoid the confounding effects of segregating nuclear alleles, an
      inbred maize line was utilized. Cytolines with Z. mays teosinte cytoplasms were
      generally indistinguishable from maize. However, cytolines with cytoplasm from
      the more distantly related Z. luxurians, Z. diploperennis, or Z. perennis
      exhibited a plethora of differences in growth, development, morphology, and
      function. Significant differences were observed for 56 of the 58 characters
      studied. Each cytoline was significantly different from the inbred line for most
      characters. For a given character, variation was often greater among cytolines
      having cytoplasms from the same species than among those from different species.
      The characters differed largely independently of each other. These results
      suggest that the cytoplasm contributes significantly to a large proportion of
      plant traits and that many of the organelle genes are phenotypically important.

PMID- 15731528
TI  - Pulse wave velocity predicts cardiovascular mortality: findings from the Hawaii
      Los Angeles-Hiroshima study.
AB  - BACKGROUND: Arterial stiffness measurements, generally from pulse wave velocity
      (PWV), are widely used with little knowledge of their relationship to long-term
      cardiovascular mortality in general populations. METHODS AND RESULTS: We studied
      a cohort of 492 Japanese-Americans living in Hawaii (mean age: 63.7 +/-8.8 years)
      to assess the relationship between PWV and cardiovascular disease mortality and
      all-cause mortality. During the 10-year follow-up, 43 patients died (14 from
      cardiovascular events). The cohort was divided into 2 groups by the cut-off value
      of PWV (9.9 m/s) represented in the receiver operating characteristic curve. The
      risk ratio for PWV values >9.9 m/s to all-cause mortality was 1.28 [95%
      confidence interval (CI): 1.14-1.42], and adjusted for other risk factors this
      ratio was 1.42 (95% CI: 0.96-2.11). The corresponding risk ratios for
      cardiovascular mortality was 4.46 (95% CI: 1.61-12.32) and 4.24 (95% CI: 1.39
      12.96), respectively. CONCLUSIONS: The present study demonstrated that an
      increased PWV value is associated with future cardiovascular disease death in
      Japanese-Americans living in Hawaii.

PMID- 15731520
TI  - The first steps of transposable elements invasion: parasitic strategy vs. genetic
      drift.
AB  - Transposable elements are often considered as selfish DNA sequences able to
      invade the genome of their host species. Their evolutive dynamics are complex,
      due to the interaction between their intrinsic amplification capacity, selection
      at the host level, transposition regulation, and genetic drift. Here, we propose
      modeling the first steps of TE invasion, i.e., just after a horizontal transfer,
      when a single copy is present in the genome of one individual. If the element has
      a constant transposition rate, it will disappear in most cases: the elements with
      low-transposition rate are frequently lost through genetic drift, while those
      with high-transposition rate may amplify, leading to the sterility of their host.
      Elements whose transposition rate is regulated are able to successfully invade
      the populations, thanks to an initial transposition burst followed by a strong
      limitation of their activity. Self-regulation or hybrid dysgenesis may thus
      represent some genome-invasion parasitic strategies.

PMID- 15731529
TI  - Long-term changes in coronary artery aneurysms in patients with Kawasaki disease:
      comparison of therapeutic regimens.
AB  - BACKGROUND: There are few studies of the therapeutic regimens for the prevention
      of stenotic transformation of aneurysms in Kawasaki disease (KD). The aim of this
      study was to assess the prophylactic effect of combined therapy in the acute
      stage and convalescent- to chronic-stage against the formation of stenotic
      lesions. METHODS AND RESULTS: In 85 patients, 103 giant aneurysms (ANl), 46
      medium-sized aneurysms (ANm), and 13 small aneurysms (ANs) were analyzed. With
      respect to therapy in the acute stage, no localized stenosis of ANl in the left
      coronary artery was noted in patients who received high-dose gamma globulin
      therapy (G). For ANm, the group (G) showed a significantly higher regression rate
      than the aspirin group and steroids group. Furthermore, no coronary artery
      occlusion/recanalization of ANl occurred with the prophylactic regimen of aspirin
      and warfarin {aw}. Prophylaxis {aw} and the prophylactic regimen of aspirin alone
      {a} significantly lowered the incidence compared with either the prophylactic
      regimen of warfarin {w} or no prophylaxis {n}. However, no significant
      differences were noted between prophylaxis {w} and {n}. CONCLUSIONS: High-dose
      gamma globulin therapy in the acute stage of KD is the first choice for the
      prevention of stenotic transformation. Prophylaxis {aw} is recommended for ANl.

PMID- 15731530
TI  - Long-term course and clinical characteristics of ventricular tachycardia detected
      in children by school-based heart disease screening.
AB  - BACKGROUND: The prognosis of ventricular tachycardia (VT) in children with overt
      heart disease is generally good, so the aim of this study was to review the
      prognosis and necessity of treatment of VT that detected by school-based heart
      disease screening. METHODS AND RESULTS: Of the 48 cases of pediatric VT that have
      been followed for 2-30 years, 17% were diagnosed at the first school-based
      screening test (12-lead ECG at rest) and the remainder who had premature
      ventricular contractions (PVC) on the resting 12-lead ECG required Holter ECG
      test and exercise stress ECG test to detect VT. In 90% of cases, VT in healthy
      children is idiopathic non-sustained VT and more than half of the present cases
      showed natural disappearance of the VT during follow up. In particular, cases of
      monomorphic PVC or maximum PVC runs less than 5 had a good prognosis. The cases
      of polymorphic VT and VT with heart disease continued for the long term.
      CONCLUSION: Treatment is unnecessary for monomorphic VT with the maximum number
      of salvos less than 5. The necessity for treatment depends on the symptoms and
      profile of the VT. The prognosis for polymorphic VT and underlying heart disease
      is not good and may require implantable cardioverter defibrillator.

PMID- 15731531
TI  - Clinical characteristics of heart disease patients with a good prognosis in spite
      of markedly increased plasma levels of type-B natriuretic peptide (BNP):
      anomalous behavior of plasma BNP in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Although it is not rare to encounter patients with plasma B-type
      natriuretic peptide (BNP) levels unequivalent to the severity of heart failure
      (HF), there has been little investigation to clarify the causative background of
      this phenomenon. METHODS AND RESULTS: Among the 1,838 outpatients whose plasma
      BNP was measured, persistently increased levels of BNP above 500 pg/ml was
      observed for more than 6 months in 14 subjects with few HF symptoms. Among these,
      all of 4 patients without any following cardiac events (E-/high) for 12 months
      showed hypertrophic nonobstructive cardiomyopathy (HNCM). When we compared the
      clinical parameters of these patients with those of 22 HNCM patients without any
      following cardiac events whose plasma BNP levels were less than 200 pg/ml, there
      were only 2 clinical characteristics to be distinguished: (i) plasma renin
      activity (PRA) and norepinephrine (NE) levels were low in spite of markedly
      increased levels of plasma BNP in E-/high HNCM; and (ii) echocardiographic
      investigation revealed that only global left atrial fractional shortening was
      significantly lower in E-/high HNCM. CONCLUSIONS: Plasma BNP levels do not always
      reflect the severity of HF in HNCM. It might be considered to utilize other
      clinical parameters such as NE and PRA to recognize HF severity in such patients.

PMID- 15731532
TI  - Multicenter prospective investigation on efficacy and safety of carperitide for
      acute heart failure in the 'real world' of therapy.
AB  - BACKGROUND: Efficacy and safety assessments for carperitide (alpha-human atrial
      natriuretic peptide) in previous clinical trials have not mentioned its
      limitations in practice as therapy for acute heart failure. METHODS AND RESULTS:
      A 6-year prospective open-label registry analysis was conducted in the 'real
      world' of therapy for 3,777 patients with acute heart failure (male 57%, median
      age 73) treated with 0.085 microg . kg(-1) . min(-1) (median, interquartile 0.05
      0.1) of carperitide for 65 h (median, interquartile 22-142); 51% were assessed as
      class III or IV according to the Killip classification; 82% of the patients were
      assessed as clinically improved after carperitide treatment. The efficacy
      limitation was related to the underlying disease (acute myocardial infarction),
      severity of Killip classification (Class IV), and renal function disturbance. The
      efficacy was significantly higher in patients with decompensated chronic heart
      failure (ie, cardiomyopathy, valvular diseases, and hypertensive heart disease).
      Incidence of adverse events was 16.9%, the most frequent being blood pressure
      lowering (9.5%), which occurred in the first 3 h of infusion, with 96% of
      patients recovering or improving without specific treatment. Logistic regression
      analysis revealed that factors predicting mortality (11.4%) during 7 days of
      follow-up were age, Killip classification, renal function disturbance, low blood
      pressure and use of vasopressors. CONCLUSION: The clinical condition improved in
      82% of patients treated with carperitide. Based on these findings, minute
      strategy will be established for carperitide therapy within the strata of patient
      characteristics that may predict the prognosis.

PMID- 15731534
TI  - Initial and follow-up results of the BiodivYsio phosphorylcholine coated stent
      for treatment of coronary artery disease.
AB  - BACKGROUND: The BiodivYsio stent is coated with a phosphorylcholine containing
      copolymer to confer biocompatibility. The present study was designed to assess
      the safety and efficacy of this coronary stent for the treatment of native
      coronary artery lesions in patients with coronary artery disease. METHODS AND
      RESULTS: From August 2001 to April 2003, 130 patients with lesions were treated
      with this stent. Elective stenting (ES) was performed in 90 patients and bailout
      stenting (BS) was performed in 40 patients with small vessels. Pre-interventional
      reference diameter, minimal lumen diameter (MLD), and lesion length were 2.68+/
      0.51, 1.00+/-0.30, 12.78+/-4.32, respectively, and post-interventional MLD was
      2.24+/-0.45 mm. The initial success rate was 100%. However, 2 non-Q-wave
      myocardial infarctions (non-QMI) occurred post-procedurally due to branch
      occlusion. A 6-month follow-up was performed. No subacute thrombosis occurred. In
      the ES group, 1 non-QMI occurred after the interventional procedure in another
      vessel. There was no death or coronary artery bypass grafting (CABG). The
      angiographic restenosis rate was 15.6%. In the BS group, there was no death,
      myocardial infarction or CABG. The angiographic restenosis rate was 17.5%.
      CONCLUSION: The BiodivYsio stent is safe and effective as a primary device for
      the treatment of native coronary artery lesions, especially in small vessels.

PMID- 15731533
TI  - Serum thioredoxin and alpha-tocopherol concentrations in patients with major risk
      factors.
AB  - BACKGROUND: Oxidative stress, which is thought to be increased in subjects with
      various coronary risk factors, induces thioredoxin (TRX), a redox-active protein.
      METHODS AND RESULTS: To determine whether oxidative stress is increased, serum
      concentrations of both TRX and alpha-tocopherol (vitamin E) were determined in 12
      control subjects without any coronary risk factors (CONTROL), 6 current smokers
      (SMOKING), 19 hypertensive patients (HT), 7 hypercholesterolemic patients (HC)
      and 14 subjects with multiple risk factors (MULTIPLE). Patients with diabetes
      mellitus were not included. The serum TRX concentrations (mean +/- SD ng/ml) were
      significantly higher in SMOKING (41+/-10), HT (41+/-17), HC (48+/-15) and
      MULTIPLE (46+/-15) than in CONTROL (24+/-11). The serum alpha-tocopherol
      concentrations (mg/g lipids) were not significantly different among CONTROL
      (4.0+/-0.7), SMOKING (4.0+/-0.8), HT (4.1+/-0.6) and HC (4.2+/-0.6), although the
      concentration was significantly lower in MULTIPLE (3.3+/-0.7) than in any of the
      other study groups. CONCLUSIONS: SMOKING, HT, HC and MULTIPLE had significantly
      higher serum TRX concentrations than CONTROL, suggesting increased oxidative
      stress. MULTIPLE had a lower serum concentration of antioxidant alpha-tocopherol
      than any of the other study groups, suggesting impaired or exhausted defense
      against chronic oxidative stress in the presence of the multiple risk factors.

PMID- 15731535
TI  - Incremental value of regional wall motion analysis immediately after exercise for
      the detection of single-vessel coronary artery disease: study by separate
      acquisition, dual-isotope ECG-gated single-photon emission computed tomography.
AB  - BACKGROUND: Although the detection of wall motion abnormalities gives incremental
      value to myocardial perfusion single-photon emission computed tomography (SPECT)
      in the diagnosis of extensive coronary artery disease (CAD) and high-grade single
      vessel CAD, whether or not it is useful in the diagnosis of mild, single-vessel
      CAD has not been studied previously. METHODS AND RESULTS: Separate acquisition,
      dual isotope ECG-gated SPECT was performed in 97 patients with a low likelihood
      of CAD (Group 1) and 46 patients with single-vessel CAD (Group 2). Mild CAD was
      defined by stenosis of 50-75% (Group 2a, n=22) and moderate to severe CAD was
      defined by stenosis >/=76% (Group 2b, n=24). Myocardial perfusion and wall motion
      were graded by a 5 point-scale, 20-segment model. The sensitivity of myocardial
      perfusion alone was 50% for Group 2a, 83% for Group 2b and 67% for Group 2 as a
      whole. The overall specificity was 90%. When the wall motion analysis was
      combined, the sensitivity was increased to 82% in Group 2a and 92% in Group 2b.
      CONCLUSION: The ability to detect a wall motion abnormality immediately after
      exercise gives incremental diagnostic value to myocardial perfusion SPECT in the
      identification of mild, single-vessel CAD.

PMID- 15731536
TI  - Myocardial protective effects of nicorandil during percutaneous coronary
      intervention in patients with unstable angina.
AB  - BACKGROUND: The purpose of the study was to prospectively evaluate the protective
      effect of nicorandil during percutaneous coronary intervention (PCI) in patients
      with unstable angina (UAP). METHODS AND RESULTS: Two hundred patients (61+/-10
      year-old, male 143) diagnosed with UAP at an emergency medical center were
      randomly assigned to 2 groups: intravenous isosorbide dinitrate, Group I (n=100),
      or intravenous nicorandil, Group II (n=100). PCI was performed 12-48 h after
      infusion of each agent. Serum concentrations of creatine kinase-MB (CK-MB),
      cardiac troponin T (cTnT), and I (cTnI) were measured before and 6, 12, 24 h
      after PCI. Patients with non-coronary chest pain, requiring emergency coronary
      angiogram, temporary pacemaker or glycoprotein IIb/IIIa receptor blocker were
      excluded. PCI was successfully performed in 96 patients (Group I=54, 61.7+/-8.2
      years, 32 males; Group II=42, 60.4+/-11.7 years, 27 males). No significant
      differences in clinical or coronary angiographic characteristics were observed
      between the 2 groups. The concentration of CK-MB was elevated in 9 patients (17%)
      of Group I and 6 (14%) of Group II, cTnT in 16 (30%), 6 (14%) and cTnI in 25
      (46%), 9 (21%) after PCI. Elevation of any troponin was less frequent in Group II
      [28/54 (52%) vs 10/42 (24%) patients, p=0.01]. Major adverse coronary events
      during the 6-month clinical follow-up occurred in 9 (17%) of Group I and 5
      patients of Group II (12%, p=NS). Follow-up echocardiography revealed lower left
      ventricular ejection fraction in Group I than in Group II (65.4+/-7.2% vs 71.0+/
      6.7%, p=0.03). CONCLUSION: Nicorandil has a myocardial protective effect during
      PCI in patients with UAP.

PMID- 15731537
TI  - Prediction of functional improvement of ischemic myocardium with (123I-BMIPP
      SPECT and 99mTc-tetrofosmin SPECT imaging: a study of patients with large acute
      myocardial infarction and receiving revascularization therapy.
AB  - BACKGROUND: (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) is
      assumed to be the most useful method of evaluating the viability of the
      myocardium, but its use is limited by the need for a cyclotron. In the present
      study, the ability of a combination of (99m)Tc-tetrofosmin (TF) and (123)I-beta
      methyliodophenyl pentadecanoic acid (BMIPP) single-photon emission computed
      tomography (SPECT), a combination of (18)F-FDG PET and (123)I-BMIPP SPECT, and a
      combination of (18)F-FDG PET and (99m)Tc-TF SPECT were compared to predict
      functional improvement of ischemic myocardium after a large acute myocardial
      infarction (AMI). METHODS AND RESULTS: Ten patients with large AMI were studied
      by (99m)Tc-TF SPECT, (123)I-BMIPP SPECT and (18)F-FDG PET within 3 weeks. Six
      months later, (99m)Tc-TF imaging was performed. All patients underwent successful
      revascularization, and had no restenosis. Regional tracer uptake was scored using
      a 4-point scale in 20 segments of the SPECT and PET images. When the defect score
      of (123)I-BMIPP SPECT exceeded the defect score of (99m)Tc-TF SPECT or (18)F-FDG
      PET by 1 point or more, and when the defect score of (99m)Tc-TF SPECT exceeded
      the defect score of (18)F-FDG PET by 1 point or more, the segment was considered
      to show mismatching. When the defect score was the same in 2 tracers, the segment
      was considered to show matching. (99m)Tc-TF imaging at 3 weeks and 6 months used
      quantitative gated SPECT (QGS) to score wall motion using a 6-point scale (-1=
      dyskinesis, 0= akinesis, 1= severe hypokinesis, 2= moderate hypokinesis, 3= mild
      hypokinesis, and 4= normokinesis). The sensitivity of the combination of (123)I
      BMIPP and (99m)Tc-TF imaging in predicting functional improvement was 61%, that
      of (18)F-FDG PET and (123)I-BMIPP SPECT was 94%, and that of (18)F-FDG PET and
      (99m)Tc-TF SPECT was 76%. The specificity of the combination of (123)I-BMIPP and
      (99m)Tc-TF imaging in predicting functional improvement was 83%, that of (18)F
      FDG PET and (123)I-BMIPP SPECT was 40%, and that of (18)F-FDG PET and (99m)Tc-TF
      SPECT was 49%. The accuracy of the combination of (123)I-BMIPP and (99m)Tc-TF
      imaging in predicting functional improvement was 70%, that of (18)F-FDG PET and
      (123)I-BMIPP SPECT was 71%, and that of (18)F-FDG PET and (99m)Tc-TF SPECT was
      63%. CONCLUSION: The combination of (123)I-BMIPP and (99m)Tc-TF imaging is a
      practical modality for predicting the functional improvement of ischemic
      myocardium after a large AMI.

PMID- 15731538
TI  - Detection of anomalous origins of the coronary artery by means of multislice
      computed tomography.
AB  - BACKGROUND: Anomalous origins of the coronary artery are rare, but may cause
      myocardial ischemia and sudden death. Thus, their reliable identification is
      crucial for any imaging method that attempts coronary artery visualization and of
      those available multislice computed tomography (MSCT), which provides excellent
      spatial resolution, may be the most promising. METHODS AND RESULTS: In
      consecutive 1,153 patients, MSCT identified 5 patients (0.43 %) with an anomalous
      origin of the coronary artery. The left circumflex artery (LCX) originated from
      the right sinus of Valsalva in 1 patient, and the right coronary artery
      originated from the left sinus of Valsalva and coursed between the aortic root
      and the pulmonary artery in 3 patients. In 1 patient, MSCT identified the absence
      of the LCX and high-grade atherosclerotic stenosis in the right coronary artery.
      CONCLUSION: MSCT can detect the anomalous origin and course of the coronary
      artery in relation to the great vessels. It is also useful for identifying
      atherosclerotic coronary artery disease superimposed on the anomalous vascular
      system.

PMID- 15731539
TI  - Intravascular ultrasound predictors of side branch occlusion in bifurcation
      lesions after percutaneous coronary intervention.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) of bifurcation lesion has
      been associated with a low success rate and a high incidence of procedural
      complications, including side branch occlusion and myocardial infarction. It
      remains controversial whether preintervention intravascular ultrasound (IVUS)
      findings can help to identify side branches likely to occlude after PCI of
      bifurcation lesions. METHODS AND RESULTS: From our IVUS database we identified 81
      bifurcation lesions in 72 patients. Side branches were classified into 2 groups:
      group 1 had ostial side branch stenosis due to atherosclerotic plaque only in the
      main vessel (n=61), and group 2 had plaque truly involved in the side branch
      ostium (n=20). There was no significant difference between the 2 groups in the
      extent of ostial stenosis as assessed by angiography. After PCI, 7 side branches
      occluded in group 2, compared with 5 side branches occluded in group 1 (35% vs
      8%, p=0.003). CONCLUSION: Ostial plaque distribution as assessed by IVUS may be
      one of the consistent predictors of side branch occlusion after PCI.

PMID- 15731540
TI  - Prospective randomized trial for optimal prophylactic treatment of the upper
      gastrointestinal complications after open heart surgery.
AB  - BACKGROUND: Upper gastrointestinal bleeding is a lethal complication after open
      heart surgery. We designed a prospective randomized trial to test the efficacy of
      different antisecretory agents to prevent upper gastrointestinal disease after
      operation. METHODS AND RESULTS: A total of 210 patients were divided into 3
      groups: group I had 70 patients who had mucosal protection (teprenone 150
      mg/day), group II had 70 patients who had histamine2-receptor antagonist
      (ranitidine 300 mg/day), and group III included 70 patients who had a proton pump
      inhibitor (rabeprazole 10 mg/day). Gastric fiberscopy was used in all patients
      postoperatively during days 5 to 7. We compared the 3 groups in terms of
      endoscopic findings. Four patients (5.7%) had gastric bleeding complications in
      each of groups I and II; 2 died of coagulopathy. In group III no patients had
      gastric bleeding. The incidence of hemorrhagic gastritis was significantly higher
      in groups I (22.9%) and II (15.7%) than in III (2.9%) (p=0.0003). The incidence
      of active ulcers was also significantly higher in groups I (28.6%) and II (21.4%)
      than in III (4.3%) (p=0.0001). CONCLUSIONS: Early medication postoperative by a
      proton pump inhibitor was shown to be the most effective treatment and indeed
      might be described as mandatory to prevent upper gastrointestinal diseases after
      open heart surgery.

PMID- 15731541
TI  - Efficacy of acute inhalation of nitric oxide in patients with primary pulmonary
      hypertension using chronic use of continuous epoprostenol infusion.
AB  - BACKGROUND: There have only been a few reports published on combination therapy
      for patients with primary pulmonary hypertension (PPH). METHODS AND RESULTS:
      Fifteen patients with PPH (4 men and 11 women, 34.5+/-12.1 years old) had
      received chronic administration of epoprostenol and the additive effects of
      inhaled nitric oxide (NO) and the hemodynamic changes were evaluated. In
      addition, the difference in the effect of acute NO loading before and after the
      epoprostenol therapy was compared in 6 of these patients. Under chronic use of
      epoprostenol, mean pulmonary arterial pressure, mean right atrial pressure and
      pulmonary vascular resistance were decreased with acute inhalation of NO.
      However, cardiac output, mean aortic pressure and systemic vascular resistance
      were unchanged. As a result, the pulmonary to systemic vascular resistance ratio
      was reduced. Moreover, after chronic use of epoprostenol, the change (delta) in
      cardiac output with NO inhalation was increased and the NO-induced decrease in
      pulmonary vascular resistance was augmented compared to those before the
      induction. CONCLUSION: Nitric oxide inhalation further improved the hemodynamics
      when combined with chronic use of epoprostenol in PPH patients. These results
      suggest the possibility that combination therapies can be used in the treatment
      for PPH patients.

PMID- 15731542
TI  - Reference value for C-reactive protein and its distribution pattern in thai
      adults.
AB  - BACKGROUND: To set a reference value for high-sensitivity C-reactive protein (hs
      CRP) in a healthy Thai population and study the effect of time, gender and age on
      that value. METHODS AND RESULTS: Three hundred and sixty-four subjects, aged
      between 18 and 74 years, comprising 185 men and 279 women, were studied. Another
      10 healthy subjects, aged between 18 and 54 years, were recruited for the study
      of circadian variation in hs-CRP over the days of the week and the months of a
      year. The reference value for the Thai adults in the present study was 1.8 mg/L,
      range 0.2-7.9 mg/L. There was no significant difference in the hs-CRP
      concentration because of region, time, gender or age (p>0.05), nor was the value
      affected by time. CONCLUSION: The determination of hs-CRP can be performed at any
      time and the hs-CRP value determined by this study can be used as the reference
      for Thai adults.

PMID- 15731543
TI  - Refractory gradient is responsible for the increase in ventricular vulnerability
      under sodium channel blockade.
AB  - BACKGROUND: Previous studies have shown that sodium channel (I(Na)) blockade
      increases ventricular vulnerability; however, there were differences in the
      degree of the increase. Because the vulnerable window (VW) is altered by the type
      of preshock refractory gradient (RG), the hypothesis was that the differences in
      the arrhythmogenesis of I(Na) blockade result from the different types of
      preshock RG employed. METHODS AND RESULTS: Simulations of regio(Na)l electric
      shock following constant pacing stimuli in 2-dimensional bidomain myocardial
      sheets under I(Na) blockade were conducted using 3 types of preshock RG:
      longitudinally tilted (LRG), transversely tilted (TRG), and non-tilted RG (NRG).
      The increase in the degree of I(Na) blockade almost linearly decreased the
      conduction velocity. The action potential duration in the LRG and TRG cases was
      non-linearly shortened with the increase in INa blockade because of electrotonic
      influences, whereas in the case of NRG it was slightly prolonged. In both LRG and
      TRG cases, the VW for reentry induction by electric shock was considerably
      widened by the INa blockade; however, this was not the case for NRG in which the
      VW was rather narrowed by the INa blockade. CONCLUSION: The type of preshock RG
      alters the degree of the increase in ventricular vulnerability under INa
      blockade.

PMID- 15731544
TI  - Increased constriction of the ductus arteriosus by dexamethasone, indomethacin,
      and rofecoxib in fetal rats.
AB  - BACKGROUND: To find a better treatment for patent ductus arteriosus (PDA) in
      premature infants, the present study investigated the synergism of clinical doses
      of dexamethasone, indomethacin, and rofecoxib, a selective cyclooxygenase-2 (COX
      2) inhibitor, on the fetal ductus arteriosus (DA) in rats. METHODS AND RESULTS:
      Dexamethasone (0.3 mg/kg), indomethacin (0.3 mg/kg), and rofecoxib (0.3 mg/kg),
      alone or in combination, were administered to preterm (d19) and near-term (d21)
      fetal rats. The ratio of the inner diameter of the DA to that of the main
      pulmonary artery (PA) (DA/PA) was studied at 2, 4 and 8 h after drug
      administration, using a rapid whole-body freezing method. In near-term rats, the
      combined administration of dexamethasone and indomethacin caused severe
      constriction, with a DA/PA ratio of 0.52+/-0.08 at 8 h, whereas the DA/PA ratios
      were 0.83+/-0.03 and 0.90+/-0.02 with dexamethasone and indomethacin,
      respectively. Combined administration of dexamethasone and rofecoxib also caused
      severe constriction, with a DA/PA ratio of 0.64+/-0.07 at 8 h, compared with the
      DA/PA ratio of 0.92+/-0.03 with rofecoxib alone. CONCLUSIONS: Combined therapy
      may be an option in the medical management of PDA in premature infants before
      considering surgical treatment.

PMID- 15731545
TI  - Unilateral renal hypoplasia associated with bicuspid aortic valve.
AB  - A 20-year-old man with congestive heart failure (CHF) and hypertension (HT) was
      admitted to hospital. Ultrasonic echocardiography showed that he had aortic
      stenosis caused by a bicuspid aortic valve. The plasma renin concentration was
      slightly elevated, and enhanced magnetic resonance imaging and renography
      revealed a hypoplastic kidney that had almost lost its normal function. It is
      postulated that the increased afterload and preload of the left ventricle induced
      by both of these abnormalities contributed to the onset of CHF and HT.
      Pharmacological therapy alone failed to control the CHF and HT, but surgical
      removal of the hypoplastic kidney was effective in reducing the plasma renin
      concentration and treating the CHF and HT.

PMID- 15731546
TI  - Mechanical ventricular assist system required for sustained severe cardiac
      dysfunction secondary to peripartum cardiomyopathy.
AB  - A 29-year old woman developed severe congestive heart failure in the first week
      after an uneventful full-term delivery. Despite intense medical treatment over
      the next 6 months, her heart failure symptoms gradually worsened and she
      eventually developed cardiogenic shock. She successfully underwent the
      implantation of a left ventricular assist system, but because there was no sign
      of recovery of ventricular function, she was placed on the waiting list for heart
      transplantation. After 143 days of support, she suffered from brain hemorrhage,
      and eventually died after a total of 321 days of left ventricular support.
      Postmortem examination of the myocardium showed sustained diffuse fibrosis and no
      inflammatory reaction. This case implies that with severe peripartum
      cardiomyopathy heart transplantation should be considered without delay even if a
      mechanical assist system is available.

PMID- 15731547
TI  - Ventricular septal perforation in a patient with takotsubo cardiomyopathy.
AB  - An 84-year-old woman was admitted with anorexia and because the serum cardiac
      markers, electrocardiogram and echocardiography suggested acute myocardial
      infarction she underwent emergency cardiac catheterization. Coronary angiography
      revealed no significant coronary artery stenosis, but left ventriculography
      revealed akinesis of the left ventricular apex with shunt flow to the right
      ventricle. The diagnosis was a rare case of takotsubo cardiomyopathy complicated
      by ventricular septal perforation. The patient died of cardiogenic shock on the
      day of admission day.

PMID- 15731548
TI  - Spontaneous multiple arterial dissections presenting with renal infarction and
      subarachnoid hemorrhage in a patient under treatment for infertility.
AB  - A 36-year-old woman developed multiple spontaneous arterial dissections in both
      renal arteries, the carotid artery, superior mesenteric artery, and vertebral
      artery, but not the aorta, and she suffered a renal infarction and subarachnoid
      hemorrhage within a short period of time. She had been undergoing frequent
      injections of human chorionic gonadotropin and human menopausal gonadotropin,
      together with oral estrogen therapy, during a 5-year infertility treatment
      regimen. As she had no other history of any disorder affecting the arterial
      walls, this therapy is suspected to have caused the multiple arterial
      deformities. Although cases of isolated arterial dissection are occasionally
      reported, it is rare for multiple dissections and serious symptoms to occur
      simultaneously.

PMID- 15731549
TI  - Detection of renal dysfunctions in family members of patients with Balkan endemic
      nephropathy.
AB  - BACKGROUND/AIM: Recent studies have questioned whether new cases of Balkan
      endemic nephropathy (BEN) are occurring. The aim of the present study was to find
      out whether new members with renal dysfunctions can be identified among family
      members of BEN patients from the Kolubara region. METHODS: The study included 47
      family members of 5 BEN patients on hemodialysis (HD) and 17 members of 3 non-BEN
      patients on HD. Their medical and epidemiological histories were taken, an
      objective survey made, and all persons were examined for global and tubular
      kidney function. RESULTS: Seven BEN family members (2 with previously known BEN)
      had creatinine clearance (Ccr) below the 75th percentile rank according to sex
      and age. All non-BEN family members had normal Ccr and no evidence of previous
      renal disorders. Hypertension was found in 20 (43%) BEN and 6 (35%) non-BEN
      family members. No significant differences in the frequency of renal function
      disorders (proteinuria, alpha1-microglobulinuria, urine specific gravity,
      osmolality, functional excretion of sodium, tubular phosphate resorption) or
      anemia were found between the groups. Renal disorders were detected in 18 BEN
      family members without previously detected disease, 3 of whom fulfilled criteria
      for a diagnosis of BEN and another 2 for BEN-suspected persons. CONCLUSION: New
      cases of BEN are still arising among the affected families in the Kolubara
      region.

PMID- 15731550
TI  - Pyruvate in the correction of intracellular acidosis: a metabolic basis as a
      novel superior buffer.
AB  - The review focuses on biochemical metabolisms of conventional buffers and
      emphasizes advantages of sodium pyruvate (Pyr) in the correction of intracellular
      acidosis. Exogenous lactate (Lac) as an alternative of natural buffer,
      bicarbonate, consumes intracellular protons on an equimolar basis, regenerating
      bicarbonate anions in plasma while the completion of gluconeogenesis and/or
      oxidation occurs via tricarboxylic-acid cycle in mitochondria mainly in liver and
      kidney, or heart. The general assumption that Lac is 'metabolized to bicarbonate'
      in liver to serve as a buffer has been questioned. Pyr as a novel buffer would be
      superior to conventional ones in the correction of metabolic acidosis. Several
      likely biochemical mechanisms of Pyr action are discussed. Experimental evidence,
      in vivo, strongly suggested that Pyr would be particularly efficient in the
      correction of severe acidemia: type A lactic acidosis, hypercapnia with cardiac
      arrest, and diabetic and alcoholic ketoacidosis in animal experiments and clinic
      settings. Because of its multi-cytoprotection, Pyrs not only correct acidosis,
      but also benefit theunderlying dysfunction of vital organs. In addition, Pyr is
      also a potential buffer component of dialysis solutions. However, the instability
      of Pyr in aqueous solutions restricts its clinical applications as a therapeutic
      agent. Attempts to create a stable Pyr preparation are needed.

PMID- 15731551
TI  - Usefulness of cardiac troponin T and echocardiography in the diagnosis of hypoxic
      myocardial injury of full-term neonates.
AB  - BACKGROUND: Perinatal asphyxia constitutes a significant problem influencing
      neonatal mortality and morbidity. OBJECTIVES: The aim of the present work was to
      provide evidence of the usefulness of cardiac troponin T (cTnT) and
      echocardiographic investigations in the diagnosis of heart damage in full-term
      infants after intrauterine hypoxia. MATERIAL AND METHODS: The subjects were 39
      asphyxiated and 44 term infants without fetal anoxia. Quantitative determinations
      of cTnT were performed between 12 and 24 h of life. Two-dimensional Doppler and
      color Doppler studies were performed at the bedside. We evaluated fractional
      shortening (FS), cardiac output (CO), cardiac index (CI), tricuspid (TI) and
      mitral (MI) insufficiency. RESULTS: Asphyxiated infants presented increased cTnT
      (mean 0.141+/-0.226 vs. 0.087+/-0.111 ng/ml; p<0.01) and TI (38.5 vs. 11.4% of
      population; p<0.05) compared to healthy infants. CO, CI and FS remained in the
      same range. CONCLUSIONS: We found cTnT to be the most useful among accessible
      diagnostic tools used in post-hypoxic heart damage in neonates. The data from our
      relatively small population study suggest a cTnT value of >0.1 ng/ml as a
      reliable marker of myocardial injury in neonates. Further study should be
      performed to generate a receiver-operator characteristic curve to discover what
      the cut-off level should be.

PMID- 15731552
TI  - Serum alpha- and gamma-tocopherol levels in atopic mothers and their infants are
      correlated.
AB  - BACKGROUND: Vitamin E may have immunomodulatory properties beyond its antioxidant
      function. The objective here was to assess the alpha- and gamma-tocopherol status
      and its correlation between atopic mothers and their infants. METHODS: Mothers
      with atopic disease were recruited at the end of gestation and their infants were
      followed up. Serum samples from mothers and infants were collected at the
      infants' age of 1 month. Atopic dermatitis was diagnosed during the 1st year of
      life and skin prick tests were performed at 1 year. RESULTS: Infants' serum gamma
      and alpha-tocopherol to fat ratios were significantly correlated with maternal
      serum ratios (r=0.70, p<0.0001 and r=0.52, p=0.004, respectively). In infants the
      serum alpha-tocopherol/fat was higher and the gamma-tocopherol/fat ratio lower
      than in mothers. Serum tocopherol levels were not associated with skin prick test
      reactions or atopic dermatitis in the infants. CONCLUSIONS: Maternal tocopherol
      status determines that of the infant. Different tocopherol forms may have
      different serum levels and roles in the regulation of inflammatory diseases.

PMID- 15731553
TI  - Severe umbilical cord acidemia and neurological outcome in preterm and full-term
      neonates.
AB  - BACKGROUND: Severe intrauterine hypoxia-ischemia and acidemia may lead to a
      disturbed neurodevelopment. OBJECTIVES: To study the effects of acidemia at birth
      on neurodevelopment in preterm and full-term neonates. SUBJECTS AND METHODS:
      Short- and long-term outcome were studied retrospectively in 44 inborn preterms
      and 95 full-terms with severe acidemia at birth defined as a pH of the umbilical
      artery <7.00. Outcome was compared with 67 preterm and 90 full-term non-acidemic
      neonates (pH>7.15). Intraventricular hemorrhage (preterms) or seizures (both
      preterms and full-terms) were considered an adverse short-term outcome. Neonatal
      death, cerebral palsy or neurodevelopmental delay were considered an adverse long
      term outcome. RESULTS: Severe intraventricular hemorrhage (IVH) occurred in 5 of
      the 44 (11%) acidemic preterms and in none of the 67 (0%) non-acidemic preterms
      (p<0.01). Seizures were observed in 9 of the 44 (20%) and 11 of the 95 (12%)
      acidemic preterms and full-terms, respectively, and in none of the 67 (0%) and 1
      of the 90 (1%) non-acidemic preterms and full-terms, respectively (p<0.001 for
      preterms, p<0.01 for full-terms). Nine preterms (6 acidemic, 3 non-acidemic) and
      2 full-terms (both acidemic) died in the neonatal period. Adverse long-term
      outcome occurred in 32% of the acidemic preterms, in 21% of the non-acidemic
      preterms, in 7% of the acidemic full-terms and in 7% of the non-acidemic full
      terms. CONCLUSIONS: Acidemia at birth increased the occurrence of severe IVH in
      preterm neonates and seizures in both preterm and full-term neonates. However, no
      significant effect of acidemia on long-term outcome could be demonstrated.

PMID- 15731554
TI  - When to measure lipid profile after stroke?
AB  - BACKGROUND: Although acute decreases in total cholesterol (TC) are well
      documented in myocardial infarction, previous stroke studies have produced
      conflicting results. The timing of lipid estimation in ischemic stroke is
      becoming important with recent trial results indicating the benefits of statins.
      We therefore aimed to determine the optimal time for lipid measurements after
      stroke. We hypothesized that TC would acutely decrease after stroke and return to
      baseline by 12 weeks. METHODS AND RESULTS: We performed a prospective,
      observational study of 50 patients (age 68.5 +/- 11.2 years) who presented with
      acute ischemic stroke. Of these, 22 (44%) were HMG-CoA reductase (statin) naive,
      15 (30%) had already been on statins and 13 (26%) were commenced on statins. Of
      the 50 patients, 38 (76%) completed 12 weeks of follow-up, 5 died, and 7 were
      lost to follow-up. Fasting lipid profile (TC, low-density lipoprotein, high
      density lipoprotein, triglyceride) was measured <48 h, 4 weeks and 12 weeks
      following ictus. In patients who were statin naive, there was a significant
      increase in TC at the week 12 evaluation. CONCLUSIONS: Cholesterol levels in
      acute stroke are an unreliable measure of lipid status. Initiation of statins
      should ideally be based on measurements taken 12 weeks after stroke.

PMID- 15731555
TI  - Neurotrophic factor expression after focal brain ischemia preceded by different
      preconditioning strategies.
AB  - BACKGROUND: Both prolonged brain ischemia and preconditioning (PC) induce
      expression of neurotrophic factors. However, the influence of PC on their
      expression after a long-term ischemia remains vague. Previously, we have found
      various effects of PC on mRNA levels of different cytokines after focal brain
      ischemia. Thus, we investigated mRNA expression of nerve growth factor, brain
      derived neurotrophic factor (BDNF) and ciliary neurotrophic factor after 90-min
      middle cerebral artery occlusion (MCAo) preceded by ischemic or chemical PC.
      METHODS: MCAo was induced in rats using the suture method. PC had been carried
      out 3 days earlier. There were 4 experimental groups: MCAo alone; ischemic PC and
      MCAo; chemical PC and MCAo, and sham-operated rats. Expression of mRNAs in the
      ipsi- and contralateral cortex was studied by semiquantitative RT-PCR at 12 and
      24 h after MCAo. RESULTS: Despite clearly neuroprotective effects of both PC
      strategies, mRNA levels of neurotrophic factors were similar in tolerant and
      nontolerant rats. Only BDNF mRNA expression, 12 h after reperfusion, was lower
      when ischemic PC was applied prior to long-term ischemia. CONCLUSIONS: These
      results suggest that PC generally does not change the expression of neurotrophic
      factor expression after a long-term focal brain ischemia compared to the
      nontolerant state.

PMID- 15731556
TI  - Bendrofluazide fails to reduce elevated blood pressure levels in the immediate
      post-stroke period.
AB  - INTRODUCTION: Blood pressure (BP) levels, beat-to-beat blood pressure
      variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity
      are frequently abnormal following acute stroke and are associated with an adverse
      short- and long-term prognosis. Thiazide diuretics are effective antihypertensive
      agents in preventing primary and secondary stroke, but their hypotensive and
      cerebral autoregulatory effects in the immediate post-stroke period have not been
      studied. METHODS: Thirty-seven hypertensive neuroradiologically proven ischaemic
      stroke patients were randomized in a double-blind, placebo controlled, parallel
      group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of
      stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial
      BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide
      levels were measured within 70 +/- 20 h of cerebral infarction and again 7 days
      later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability
      and cardiac baroreceptor sensitivity were also calculated. RESULTS: Small, non
      significant falls were seen in casual and beat-to-beat BP levels over the 7-day
      period in both active and placebo-treated patients with no differences between
      treatments. No significant changes were seen in dynamic cerebral autoregulation
      or in cardiac baroreceptor sensitivity during the follow-up in either group.
      CONCLUSION: Following acute ischaemic stroke, the standard dose of bendrofluazide
      at 2.5 mg daily in this study sample did not lower systemic BP levels over the
      subsequent 7-day period. There was no evidence that bendrofluazide significantly
      altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post
      ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the
      standard dosage in the initial post-stroke period.

PMID- 15731557
TI  - Safety and feasibility of a lower dose intravenous TPA therapy for ischemic
      stroke beyond the first three hours.
AB  - BACKGROUND: The most common reason that patients do not receive intravenous
      tissue plasminogen activator (TPA) is the inability to meet the strict 3-hour
      treatment window. The risk/benefit ratio is more unfavorable beyond this time,
      but some patients might still benefit. We designed a pilot study with the
      hypothesis that lower dose TPA might be safe in selected patients treated beyond
      3 h. SUBJECTS AND METHODS: To determine the range of symptomatic hemorrhage and
      good outcome, we prospectively gave i.v. TPA 0.6 mg/kg up to 60 mg (15% bolus,
      85% infusion over 30 min) to patients with ischemic stroke beyond the first 3 h
      after last known to be normal. Other eligibility criteria were: NIH Stroke Scale
      > or =4, normal head CT scan, and clinical suspicion or transcranial Doppler
      (TCD) evidence of a proximal arterial occlusion. RESULTS: 28 patients were
      treated, median age 65 (range 24-88) years, median baseline NIHSS score 18 (range
      7-34) points. TPA bolus was given 372 +/- 158 min after stroke onset (range 189
      720). Symptomatic hemorrhage occurred in 3/28 (11%) patients, including 1 fatal
      bleed. Overall mortality was 6/28 (21%). Partial or complete recanalization was
      found in 8/20 (40%) TCD monitored patients within 2 h after TPA bolus. Early
      major improvement occurred in 4/28 (14%) patients. CONCLUSIONS: Lower dose i.v.
      TPA in patients presenting beyond 3 h carries a risk of intracerebral hemorrhage.
      However, recanalization with dramatic recovery can still occur.

PMID- 15731558
TI  - Cerebrovascular disease as a complication of cardiac transplantation.
AB  - BACKGROUND AND OBJECTIVES: To characterize the frequency, risk factors, clinical
      presentation and etiological subtypes of cerebrovascular diseases (CVD) following
      cardiac transplantation (CTX). METHODS: In a retrospective review of our CTX
      database (period 1984-2002), we assessed demographic data, vascular risk factors,
      surgery and donor details. We classified ischemic stroke (IS) using the clinical
      criteria of the Oxfordshire Community Stroke Project and the etiological criteria
      of the TOAST study. Logistic regression analysis and survival curves were carried
      out. RESULTS: CTX was performed in a total of 314 patients (age 46 +/- 14 years,
      78% male) and mean follow-up was 54 +/- 57 months. Twenty-two patients (7%)
      presented CVD: hemorrhagic stroke in 12%, transient ischemic attack in 28% and IS
      in 60%. CVD were early postoperative (less than 2 weeks) in 20% of patients and
      late in 80%. The clinical presentation in patients with IS was total anterior
      circulation (23.1%), partial anterior (38.4%), lacunar (15.4%) and posterior
      circulation (23.1%), and the etiological classification was large artery
      atherosclerosis (15.4%), cardioembolism (14.4%), small vessel disease (15.4%),
      unusual causes (15.4%) and undetermined cause (38.4%). The only independent
      predictor of CVD was a prior CVD event with an odds ratio of 8.2 (95% CI, 2.2
      30.2, p < 0.02). The estimated risk of CVD at 5 years was greater (p < 0.02) in
      patients with prior CVD (4.1%) than in those without (1.1%). CONCLUSIONS: CVD are
      a relatively frequent complication after CTX (7%) and usually occur in the late
      postoperative phase. CVD prior to transplantation increase the risk of CVD after
      this procedure.

PMID- 15731559
TI  - C-EPO: ready for prime-time preconditioning?

PMID- 15731560
TI  - Robotics in colorectal surgery.
AB  - Minimally invasive surgery has been shown to offer many advantages to general
      surgical patients but has not been widely adopted for colorectal disease. Initial
      fears surrounding the oncological safety of laparoscopic colectomies have largely
      subsided but the technical challenges still remain. Surgical robots or
      telemanipulators present the laparoscopic surgeon with unrivaled dexterity and
      vision, which may allow colonic resections to be completed with greater ease.
      Although initial studies suggest promising results using currently available
      systems, it will take further time for patient benefits to be proven, therefore
      justifying the greater expense of operating with this new technology.

PMID- 15731561
TI  - Treatment of non-atypic endometrial hyperplasia using thermal balloon endometrial
      ablation therapy.
AB  - BACKGROUND/AIM: Traditionally endometrial hyperplasias have been treated with
      progestins. Unfortunately, quite often hyperplasias are resistant to treatment,
      or they recur after therapy. The aim of the study was to compare traditional
      progestin administration with thermal balloon endometrial ablation in the
      treatment of non-atypic endometrial hyperplasia. METHODS: Women with endometrial
      hyperplasia (n = 34) were randomized in a 1:1 allocation ratio. Endometrial
      biopsy samples were taken 6 and 12 months after the treatment; if any signs of
      hyperplasia were detected, hysterectomy was performed. In addition, the hospital
      records were checked in September 2003 to observe for any later hysterectomy.
      Main outcome measures were recovery from hyperplasia and avoidance of
      hysterectomy. RESULTS: In patients treated with thermal ablation, the
      hyperplasias persisted at 6 or 12 months in 4 out of 17 patients, whereas the
      rate was 6 out of 17 patients in the progestin therapy group. According to
      patient records, 1 further patient treated with thermal ablation and 3 further
      patients treated with progestin were hysterectomized after the last visit. A
      total of 14 of the 34 patients (41%) have been hysterectomized so far.
      CONCLUSIONS: These preliminary results suggest that thermal balloon endometrial
      ablation therapy seems to be as effective as traditional progestin administration
      in the treatment of non-atypic endometrial hyperplasia. The hysterectomy rate
      during the follow-up period was, however, considerably high, and, therefore,
      hysterectomy might be considered even a first-choice treatment for endometrial
      hyperplasias.

PMID- 15731563
TI  - Screening for single gene genetic disease.
AB  - The screening and directed testing for genetic disease caused by single gene
      mutations is an expanding part of the overall scheme of prenatal care. In
      addition to reproductive choice, carrier screening and fetal diagnostic testing
      afford the important opportunity for preparation of the family and the delivery
      site for the birth of a fetus with a known genetic disorder. Increasingly the
      primary care provider in pregnancy bears the burden of engaging patients in
      discussions regarding available genetic tests appropriate to their family or
      personal history, their ethnic group, and with every patient for a limited but
      growing number of diseases. Ethnic-based risk identification and testing has
      expanded recently with, for example, the addition of familial dysautonomia for
      patients of Askhenazi ancestry. Widespread, or nearly universal, screening has
      emerged for cystic fibrosis and new initiatives are gaining momentum for prenatal
      maternal carrier screening for fragile X syndrome. The fruits of the human genome
      project will undoubtedly lead to the identification of more genes that underlie
      human disease. This will expand the menu of possible prenatal testing options and
      will raise the level of complexity in both counseling, testing logisitics and
      health care resource allocation.

PMID- 15731564
TI  - Influence of different haemodialysis modalities on AGE peptide levels:
      intradialytic versus long-term results.
AB  - BACKGROUND: Peptide-linked degradation products of advanced glycation end
      products (AGE peptides) accumulate in chronic haemodialysis (HD) patients and may
      contribute to a number of HD-related long-term complications, such as accelerated
      atherosclerosis. METHODS: The influence of a single HD session versus long-term
      HD on serum AGE peptides was determined. The patients were randomized to HD with
      a low-flux polysulfone (PS; F 6HPS), a high-flux PS (F 60S), a superflux PS (F
      500S), or a superflux cellulose triacetate (CTA; Tricea 150G) dialyzer. RESULTS:
      During a single HD session, both AGE peptides and reference peptides decreased
      significantly (AGE peptides: Tricea 150G -37.0 +/- 2.9%; F 6HPS -35.5 +/- 2.4%; F
      60S -39.5 +/- 4.7%, and F 500S -43.3 +/- 2.1%, p = 0.005; reference peptides:
      Tricea 150G -73.2 +/- 8.8%; F 6HPS -73.2 +/- 7.9%; F 60S -72.5 +/- 8.2%, and F
      500S -74.1 +/- 7.3%, p = 0.005). After 12 weeks of HD with the superflux CTA, the
      AGE peptide levels decreased significantly (week 1: 2.7 +/- 1.1 arbitrary units,
      week 12: 2.5 +/- 1.2 arbitrary units, decrease 7.4%; p = 0.01), whereas the AGE
      peptide levels remained unchanged after HD with each of the other three
      modalities. The reference peptide levels did not change after 12 weeks of HD.
      CONCLUSION: Although AGE peptides can be effectively removed during a single HD
      session, superflux CTA seems to be the only modality capable of reducing AGE
      peptides in the long term.

PMID- 15731565
TI  - Suppressive effects of iron on TGF-beta1 production by renal proximal tubular
      epithelial cells.
AB  - BACKGROUND: TGF-beta1, which is one of the profibrogenic cytokines, is considered
      essential for both the tubulointerstitial fibrosis found in chronic kidney
      diseases and the repair of tissue damage in acute renal injury. Iron plays an
      important part in inflammatory damage since it supplies cytotoxic hydroxyl
      radicals. The aim of the present study was to examine the direct effects of iron
      on TGF-beta1 production and the expression of 8-hydroxy-2'-deoxyguanosine (8
      OHdG), a marker of oxidative stress, by human renal proximal tubular epithelial
      cells (RPTEC). METHODS: Using human RPTEC, TGF-beta1 expression was studied by
      immunohistochemical staining, ELISA and RNase protection assays. 8-OHdG
      expression was evaluated by immunohistochemical staining. RESULTS: Ferric iron
      suppressed both TGF-beta1 secretion and mRNA expression, and enhanced 8-OHdG
      expression in RPTEC in a dose-dependent manner. Desferrioxamine, an iron
      chelator, eliminated the suppressive effect of ferric citrate on TGF-beta1
      production. CONCLUSIONS: The results suggest that iron may delay the repair of
      kidney injury during the acute inflammatory phase via a reduction in TGF-beta1
      production by RPTEC. Iron chelation may therefore be a useful strategy in the
      treatment of inflammatory kidney diseases.

PMID- 15731566
TI  - Comparison of cytotoxicity of cysteine and homocysteine for renal epithelial
      cells.
AB  - BACKGROUND: Although the cytotoxic effects of cysteine (Cys) on renal cells have
      been established, the effects of homocysteine (Hcy), which causes endothelial
      cell dysfunction, have not been well tested. We compared the direct toxicity of
      Hcy on renal tubular cells to that of Cys and examined the mechanism of cell
      toxicity. METHODS: LLC-PK1 cells were incubated with test media containing 500
      microM Cys or Hcy in the presence or absence of 100 microM copper. Lactate
      dehydrogenase release and thiobarbituric acid reactive substance were measured
      for estimating cytolysis and lipid peroxidation, respectively. The generation of
      hydrogen peroxide and hydroxyl radical, and the cell redox state were analyzed
      using the scopoletin method, salicylate-trap method, and glutathione (GSH)
      content, respectively. Superoxide dismutase, catalase, and vitamin E also were
      used for clarifying the mechanism of toxicity. RESULTS: In the presence of copper
      (+ Cu), cytolysis at 16 h was more prominent in cells exposed to Cys than Hcy. In
      accordance with cytotoxicity, lipid peroxidation at 4 h of incubation, as well as
      hydrogen peroxide and hydroxyl radical formation in a shorter incubation, were
      remarkably greater in Cys + Cu than Hcy + Cu. The addition of Hcy, but not Cys,
      decreased GSH content significantly. CONCLUSION: In the presence of copper, Cys
      was extraordinarily more cytotoxic to renal cells than Hcy. Cytotoxicity from Hcy
      may be dependent upon depletion of cellular GSH, while Cys cytotoxicity is
      primarily dependent upon the generation of reactive oxygen species and lipid
      peroxidation.

PMID- 15731567
TI  - Effects of neutral pH and reduced glucose degradation products in a new
      peritoneal dialysis solution on morphology of peritoneal membrane in rats.
AB  - BACKGROUND: In vitro studies have shown that pH and glucose degradation products
      (GDPs) in the dialysate are determinant factors for the biocompatibility of
      peritoneal dialysis (PD) treatment. The present study was thus designed to
      evaluate whether a newly developed PD solution, which features neutral pH levels
      and a low GDP concentration, influences tissue damage of the peritoneal membrane
      in an in vivo setting, and which factor is more critical to the histological
      changes. METHODS: Rats were injected 3 times per day during 1 or 4 weeks with 10
      ml of various PD fluids (group G, acidic pH, high GDPs; group S, neutral pH, low
      GDPs; or group A, acidic pH, low GDPs). When the experimental period was over,
      the mesothelial cell monolayers of the animals were taken and studied with
      population analysis, and peritoneal membranes were obtained from the abdominal
      wall for immunohistochemical examination with proliferating cell nuclear antigen
      (PCNA) and for measurement of thickness of the peritoneal specimens. RESULTS: The
      density of the mesothelial cell monolayer and the number of fibroblast-like cells
      in group S were significantly less than in group G at 1 and 4 weeks' injection.
      PCNA-positive nuclei in group S were significantly less than in group G for only
      the 1-week injection set (group G, 2.03 +/- 0.95; group S, 0.85 +/- 1.18 nuclei/1
      x 10(4) microm2). At 4 weeks, the peritoneal thickness of group S (6.32 +/- 0.53
      microm) was significantly less than that of group G (7.94 +/- 0.77 microm), There
      was no significant difference between groups S and A throughout the whole study
      period except for the result of the number of fibroblast-like cells. CONCLUSION:
      These results indicate that a PD solution with a neutral pH and low GDPs proved
      more biocompatible with the peritoneal membrane than a solution with an acidic pH
      and high GDPs. Furthermore, the level of the GDPs has more impact on tissue
      damage of the peritoneal membrane than the pH in the short term.

PMID- 15731568
TI  - Signals which build a tubule.
AB  - The phenomenon of branching morphogenesis is a fundamental process critical for
      development of several tubular organs including lung, mammary gland, and kidney.
      In the case of kidney, the ureteric bud (UB) that extends out from a pre-existing
      epithelial tube, the Wolffian duct, gives rise to the branched collecting duct
      system while the surrounding metanephric mesenchyme undergoes mesenchymal
      epithelial transition to form the proximal parts of the nephron. These events are
      mediated by several soluble factors that act in a cooperative fashion either as
      pro or anti tubulogenic factors. Among the growing list of such molecules are the
      members of the FGF, TGF-beta, and Wnt families as well as GDNF, HGF, and EGF.
      Cells respond to these soluble factors by initiating signaling pathways that
      regulate cell proliferation, cell migration and cell morphogenesis. These
      signaling pathways are also regulated in parallel by cell-cell and cell-matrix
      interactions, leading to the complex events necessary for tubule formation.
      Recent in-vitro and in-vivo studies have begun to shed light on the overall
      regulation of this phenomenon while the specific subcellular mechanisms are only
      beginning to be understood. This review focuses on our understanding of the
      morphogenic responses that regulate in-vitro tubulogenesis and how they may help
      us to ultimately understand this process in vivo in the kidney.

PMID- 15731569
TI  - Dopamine D2-receptor activation differentially inhibits N- and R-type Ca2+
      channels in Xenopus melanotrope cells.
AB  - Dopamine inhibits pituitary melanotrope cells of the amphibian Xenopus laevis
      through activation of a dopamine (D2) receptor that couples to a Gi protein.
      Activated Gi protein subunits are known to affect voltage-operated Ca2+ currents
      (ICa). In the present study we investigated which Ca2+ currents are regulated by
      D2-receptor activation and which Gi protein subunits are involved. Whole-cell
      voltage-clamp patch-clamp experiments from holding potentials (HPs) of -80 and 
      30 mV show that 28.6 and 36.9%, respectively, of the total ICa was inhibited by
      apomorphin, a D2-receptor agonist. The inhibited current had fast activation and
      inactivation kinetics. From an HP of -80 mV, inhibition of N-type Ca2+ currents
      with omega-conotoxin GVIA and R-type current by SNX-482 reduced the efficacy of
      the apomorphin-induced inhibition. From an HP of -30 mV this reduction for omega
      conotoxin GVIA was still observed. Blocking L-type current by nifedipine or P/Q
      type current by omega-agatoxin IVA did not affect apomorphin-induced inhibition
      at either HP. Our results imply that D2-receptor activation inhibits both N- and
      R-type Ca2+ currents. Using a strong depolarizing pre-pulse partially reversed
      the inhibition of the total current by apomorphin. About 50% of this inhibition
      was achieved through interaction of Gbeta/gamma proteins, and this part of the
      inhibited ICa had fast activating and inactivating kinetics. However, the other
      part of the current inhibited by D2-receptor activation may proceed through
      Galpha-PKA phosphorylation.

PMID- 15731570
TI  - Course of autism signs in the first year of life.
AB  - Autism spectrum disorders (ASD) are thought to be present right from birth, even
      if a minority of children displays a normal course during infancy followed by a
      regression during the second year of life. However, established criteria are not
      yet available to differentiate these different courses of ASD, and data coming
      from different sources have not yet been organized into a clear definition. The
      aim of this study was to elucidate the time of onset, as well as type, frequency
      and stability of symptoms during the first year of life in ASD. The behavioral
      summarized evaluation scale, applied to 40 home movies of children later
      diagnosed as having ASD, showed that most of the subjects (87.5%) display
      symptoms within the first year of life, when only a small group (12.5%) is
      completely symptom free. A group of more rated symptoms was found, constituting a
      typical pattern characterized by being withdrawn, and displaying poor social
      initiative, hypoactivity, and lack of emotional modulation. The importance of
      these findings is discussed in relation to early diagnosis and treatment.

PMID- 15731571
TI  - Histologic dating of the endometrium: accuracy, reproducibility, and practical
      value.

PMID- 15731572
TI  - EGFR mutations in non-small cell lung carcinomas may predict response to
      gefitinib: extension of an emerging paradigm.

PMID- 15731573
TI  - Parathyroid carcinoma: an overview.
AB  - Parathyroid carcinoma is a rare tumor that is responsible for <1% of cases of
      hyperparathyroidism in most parts of the world. An increased incidence of this
      tumor has been reported in patients with the hyperparathyroidism-jaw tumor (HPT
      JT) syndrome, but the etiology of most other cases is unknown. Parathyroid
      carcinomas tend to occur a decade earlier than adenomas, and the sex ratio
      approaches unity in contrast to the female preponderance of adenomas. Most
      patients with carcinomas present with marked hypercalcemia and are more likely to
      have associated bone and renal disease than those with adenomas. Although
      fibrosis and mitotic activity are common in carcinomas, these features are not
      specific for malignancy. The diagnosis of carcinoma should be restricted to those
      tumors that show invasion of blood vessels, perineural spaces, soft tissues,
      thyroid gland, or other adjacent structures or to tumors with documented
      metastases. Mutations of the HRPT2 gene (1q21-q32), which are responsible for the
      HPT-JT syndrome, have been implicated in the development of a high proportion of
      parathyroid carcinomas. A subset of patients with mutation-positive carcinomas
      have germline mutations of the HRPT2 gene. This finding suggests that some
      patients with apparent sporadic parathyroid carcinomas may have the HPT-JT
      syndrome or a variant of this syndrome. Because of the high frequency of local
      recurrence following incomplete excision, an en bloc resection is the preferred
      surgical approach for treatment of parathyroid carcinomas.

PMID- 15731574
TI  - Pitfalls in endoscopic ultrasound-guided fine-needle aspiration and how to avoid
      them.
AB  - Although a broad range of pancreatic, gastrointestinal, thoracic, and abdominal
      pathology may be sampled by endoscopic ultrasound (EUS)-guided fine-needle
      aspiration (FNA), certain difficulties tend to recur because of the frequency of
      certain sample types and because of the nature of their individual
      cytomorphologic profiles. With this in mind, we review certain pitfalls that may
      befall cytopathologists with EUS-guided FNA. We discuss the diagnosis of
      pancreatic ductal adenocarcinoma and of other pancreatic epithelioid tumors
      including pancreatic endocrine neoplasms, solid pseudopapillary tumors, and
      acinar cell carcinomas. We also discuss the diagnosis of pancreatic cystic
      neoplasia including intraductal papillary mucinous neoplasms and mucinous cystic
      neoplasms and the diagnosis of gastrointestinal mesenchymal neoplasia with
      particular attention to gastrointestinal stromal tumors. Finally, we discuss the
      interpretation of lymph node aspirates.

PMID- 15731575
TI  - Diverticulosis coli: update on a "Western" disease.
AB  - Diverticular disease affects upwards of 50% of the population over the age of 60
      years in Western countries and is becoming more common as the population ages.
      Studies from the 1970s and 1980s related its occurrence to the use of low-fiber
      diets and to the prolonged colonic transit time and increased intraluminal
      pressure associated with low-volume stools. Pulsion diverticula
      (pseudodiverticula) emerge through the thickened circular layer of the muscularis
      propria of the left colon at points of penetration of the vasa recta that supply
      the submucosa and mucosa. Complications of diverticular disease such as
      hemorrhage, diverticulitis, peridiverticular abscess, fistula, and perforation
      are well recognized. More recently, attention has been drawn to the polypoid
      prolapsing mucosal folds that may develop as the affected segment of bowel
      (usually the sigmoid) becomes shorter and to changes in the mucosa surrounding
      the diverticula and in the bowel wall that may result in confusion with
      ulcerative colitis or Crohn disease (sigmoid colitis-associated diverticulosis
      [SCAD]). Distinguishing SCAD from these entities is extremely important, and
      pathologists should be aware of the possibility of overdiagnosing chronic
      inflammatory bowel disease in biopsies or resection specimens of sigmoid colon
      with diverticular disease.

PMID- 15731576
TI  - Precursors to invasive pancreatic cancer.
AB  - Pancreatic cancer, once invasive, is almost uniformly fatal. In order to
      alleviate the dismal prognosis associated with this disease, it is imperative
      that pancreatic cancer be recognized and treated prior to invasion. Understanding
      the morphology and biology of precursor lesions of invasive pancreatic cancer has
      therefore become an issue of paramount importance. In the last decade,
      significant progress has been in the recognition and appropriate classification
      of these precursor lesions, and the current review will focus on our state-of-the
      art knowledge on this topic. Mucinous cystic neoplasms (MCNs), intraductal
      papillary mucinous neoplasms (IPMNs), and pancreatic intraepithelial neoplasia
      (PanIN) encompass the three known morphologically distinct precursors to invasive
      pancreatic cancer. In addition to discussion of the "classic" precursor entities,
      this review will also address some of the recent diagnostic controversies for
      these lesions, in particular features that distinguish IPMNs from PanIN lesions.
      Finally, the potential clinical impact of recognizing these precursor lesions in
      the context of early detection of pancreatic cancer will be discussed.

PMID- 15731583
TI  - Anesthesia and the human genome project: the quest for accurate prediction of
      drug responses.

PMID- 15731577
TI  - Cutaneous desmoplastic melanoma.
AB  - Desmoplastic melanoma (DM) is a fibrosing variant of spindle cell melanoma. It
      most often presents as an indurated lesion in chronically sun-damaged skin. Due
      to the lack of characteristic clinical features, early detection is uncommon. At
      the time of excision, the tumors usually extend into the reticular dermis or
      deeper. DM is prone to misdiagnosis. It may simulate histologically sclerosing
      melanocytic nevi as well as various benign and malignant nonmelanocytic lesions.
      There is significant morphologic variability among tumors classified as DM.
      Desmoplasia may be prominent throughout the entire tumor ("pure" DM) or represent
      a portion of an otherwise nondesmoplastic melanoma ("combined" DM). Some tumors
      show neuroma-like features with prominent nerve involvement, in which case the
      term "desmoplastic neurotropic melanoma" is used. Immunophenotypically, DMs are
      usually strongly and homogeneously positive for S-100 protein but are often
      negative or only focally positive for melanocyte differentiation antigens such as
      tyrosinase, gp100, Melan-A, and microphthalmia transcription factor. DM differs
      from conventional melanoma in its clinical course. It is associated with a higher
      tendency for local recurrence, but metastases to regional lymph nodes are less
      common. Evidence is also emerging that for patients with thick melanomas, the
      presence of a paucicellular fibrosing tumor histology (pure DM) is a favorable
      prognostic factor for survival.

PMID- 15731584
TI  - Genetic predisposition to latex allergy: role of interleukin 13 and interleukin
      18.
AB  - BACKGROUND: Occupational exposure of healthcare workers to natural rubber latex
      has led to sensitization and potentially life-threatening anaphylaxis. Although
      environmental exposure to natural rubber latex products is necessary for
      sensitization, it is not sufficient. A number of genetic factors also seem to
      contribute to the latex sensitization; however, the multigenic nature of the
      allergic phenotype has made the identification of susceptibility genes difficult.
      The current study tests the hypothesis that known functional polymorphisms in
      genes encoding interleukin 4, interleukin 13, and interleukin 18 occur in a
      higher frequency in healthcare workers with natural rubber latex allergy.
      METHODS: Four hundred thirty-two healthcare workers with occupational exposure to
      natural rubber latex were screened using a clinical history questionnaire and
      latex-specific immunoglobulin E serology. Genomic DNA was extracted from
      peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in
      candidate genes of interest. Data from cases and controls were analyzed by
      nominal logistic regression, with P < 0.05 considered significant. RESULTS: The
      latex allergy phenotype was significantly associated with promoter polymorphisms
      in IL13 -1055 (P = 0.02), IL18 -607 (P = 0.02), and IL18 -656 (P = 0.02) compared
      with nonatopic controls. CONCLUSIONS: The significant association of IL13 and
      IL18 promoter polymorphisms with latex allergy suggests a potential location for
      genetic control in the induction of latex allergy in individuals and extends the
      understanding of the genetic basis for the induction of immediate-type
      hypersensitivity in healthcare workers occupationally exposed to natural rubber
      latex.

PMID- 15731585
TI  - Response to mivacurium in patients carrying the k variant in the
      butyrylcholinesterase gene.
AB  - BACKGROUND: Mivacurium is hydrolyzed by the butyrylcholinesterase enzyme, and
      patients with hereditary changes of the enzyme often have prolonged duration of
      action of mivacurium. In this study, the authors investigated the significance of
      the most commonly occurring variant, the Kalow (K) variant, established using DNA
      analysis, for the response to mivacurium. METHODS: A total of 58 patients
      carrying either the wild-type butyrylcholinesterase or different combinations of
      the atypical (A) variant and the K variant were included. Patients who were
      homozygous for the A variant were given 0.03 mg/kg mivacurium. All other patients
      received 0.2 mg/kg mivacurium. The neuromuscular block was measured using train
      of-four nerve stimulation and mechanomyography. Genotyping was performed with
      complete nucleotide sequencing. RESULTS: Heterozygosity of the K variant
      prolonged the time to train-of-four 0.70 from 26.6 to 34.5 min (30%; not
      significant) as compared with the wild type. Heterozygosity of the K variant
      linked to the A variant prolonged the corresponding time from 32 to 42.7 min
      (33%; P = 0.03) as compared with patients who were heterozygous for solely an A
      allele. For eight patients who were homozygous for both the A and K variants, the
      time to 25% recovery was 78-89 min as compared with 44-57 min in patients who
      were homozygous for the A variant or had only one linked K variant. CONCLUSION:
      The K variant prolongs the duration of action of mivacurium. The current results
      indicate that the effect is modest when the K variant occurs heterozygously with
      the wild type or the A variant but is marked in patients who are homozygous for
      both the A and K variants.

PMID- 15731587
TI  - Screening of the entire ryanodine receptor type 1 coding region for sequence
      variants associated with malignant hyperthermia susceptibility in the north
      american population.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a life-threatening and frequently
      fatal disorder triggered by commonly used anesthetics. MH susceptibility is a
      genetically determined predisposition to the development of MH. Mutations in the
      ryanodine receptor type 1 (RYR1) gene are the major cause of MH susceptibility.
      The authors sought to develop a reliable genetic screening strategy based on
      efficient and relatively inexpensive mutation-detection procedures. METHODS: A
      cohort (n = 30) of North American MH patients and MH-susceptible individuals was
      studied. RNA and DNA extracted from muscle tissue or blood lymphocytes were used
      for analysis. The entire RYR1 coding region was amplified in 57 overlapping
      fragments and subjected to denaturing high-performance liquid chromatography
      analysis followed by direct nucleotide sequencing to characterize RYR1
      alterations. RESULTS: Nine previously reported and nine unknown RYR1 mutations
      were identified in 21 of 30 studied patients (70%). Some of the new mutations
      were located outside of known mutational "hot spots," suggesting that RYR1
      contains previously unknown mutation-prone areas requiring analysis. The North
      American MH/MH-susceptible population is characterized by a high RYR1 allelic
      heterogeneity. CONCLUSIONS: Denaturing high-performance liquid chromatography
      analysis of RNA samples extracted from the biopsied skeletal muscle followed by
      DNA sequencing is a highly efficient methodology for RYR1 mutation detection.
      This approach allows increasing the rate of mutation detection to 70% and
      identifying mutations in the entire RYR1 coding region.

PMID- 15731588
TI  - Polymorphism of mu-opioid receptor gene (OPRM1:c.118A>G) does not protect against
      opioid-induced respiratory depression despite reduced analgesic response.
AB  - BACKGROUND: The effect of a single nucleotide polymorphism of the mu-opioid
      receptor at nucleotide position 118 (OPRM1:c.118A>G) was investigated on morphine
      6-glucuronide (M6G)-induced analgesia and respiratory depression in a group of
      healthy volunteers. METHODS: Sixteen subjects of either sex received 0.4 mg/kg (n
      = 8) or 0.6 mg/kg M6G (n = 8). At regular time intervals, the isocapnic acute
      hypoxic ventilatory response, pain tolerance (derived from a transcutaneous
      electrical acute pain model), and arterial blood samples were obtained. Data
      acquisition continued for 14 h after drug infusion. Population pharmacokinetic
      pharmacodynamic sigmoid Emax models were applied to the respiratory and pain
      data. All collected data were analyzed using the statistical program NONMEM (San
      Francisco, CA). RESULTS: Four of the subjects were OPRM1:c.118GA heterozygotes,
      and the remainder of the subjects were OPRM1:c.118AA homozygotes. M6G analgesia:
      In contrast to analgesic responses in OPRM1:c.118AA homozygotes, responses were
      small and inconsistent in OPRM1:c.118GA heterozygotes and best described by the
      function Effect(t) = baseline (P < 0.01 vs. OPRM1:c.118AA homozygotes). Emax and
      C50 values in heterozygotes equaled 0.55 +/- 0.18 (or a 55% increase in current
      above baseline) and 161 +/- 42 ng/ml, respectively. M6G-induced respiratory
      depression: For the acute hypoxic response, neither Emax nor C50 (value = 282 +/-
      72 ng/ml) differed between genotypes. CONCLUSIONS: The data indicate that the
      OPRM1:c.118A>G polymorphism affects opioid analgesic and respiratory effects
      differentially. Despite reduced analgesic responses to M6G the OPRM1:c.118A>G
      single-nucleotide polymorphism does not protect against the toxic effects of the
      tested opioid. However, some caution in the interpretation of the data is needed
      because of the small sample size. Further studies are needed to explore the link
      between this polymorphism and respiratory/analgesic responses beyond the small
      human sample. In OPRM1:c.118AA homozygotes, the potency parameters differed by a
      factor of 2 for analgesic versus respiratory effect. In this respect, M6G differs
      favorably from morphine.

PMID- 15731586
TI  - Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy
      in redheads.
AB  - BACKGROUND: Anesthetic requirement in redheads is exaggerated, suggesting that
      redheads may be especially sensitive to pain. Therefore, the authors tested the
      hypotheses that women with natural red hair are more sensitive to pain and that
      redheads are resistant to topical and subcutaneous lidocaine. METHODS: The
      authors evaluated pain sensitivity in red-haired (n = 30) or dark-haired (n = 30)
      women by determining the electrical current perception threshold, pain
      perception, and maximum pain tolerance with a Neurometer CPT/C (Neurotron, Inc.,
      Baltimore, MD). They evaluated the analogous warm and cold temperature thresholds
      with the TSA-II Neurosensory Analyzer (Medoc Ltd., Minneapolis, MN). Volunteers
      were tested with both devices at baseline and with the Neurometer after 1-h
      exposure to 4% liposomal lidocaine and after subcutaneous injection of 1%
      lidocaine. Data are presented as medians (interquartile ranges). RESULTS: Current
      perception, pain perception, and pain tolerance thresholds were similar in the
      red-haired and dark-haired women at 2,000, 250, and 5 Hz. In contrast, redheads
      were more sensitive to cold pain perception (22.6 [15.1-26.1] vs. 12.6 [0-20]
      degrees C; P = 0.004), cold pain tolerance (6.0 [0-9.7] vs. 0.0 [0.0-2.0] degrees
      C; P = 0.001), and heat pain (46.3 [45.7-47.5] vs. 47.7 [46.6-48.7] degrees C; P
      = 0.009). Subcutaneous lidocaine was significantly less effective in redheads
      (e.g., pain tolerance threshold at 2,000-Hz stimulation in redheads was 11.0 [8.5
      16.5] vs. > 20.0 (14.5 to > 20) mA in others; P = 0.005). CONCLUSION: Red hair is
      the phenotype for mutations of the melanocortin-1 receptor. Results indicate that
      redheads are more sensitive to thermal pain and are resistant to the analgesic
      effects of subcutaneous lidocaine. Mutations of the melanocortin-1 receptor, or a
      consequence thereof, thus modulate pain sensitivity.

PMID- 15731589
TI  - Genotyping the butyrylcholinesterase in patients with prolonged neuromuscular
      block after succinylcholine.
AB  - BACKGROUND: Succinylcholine remains the standard neuromuscular blocking drug for
      tracheal intubation in emergency situations. The short duration of action is due
      to its rapid hydrolytic degradation by butyrylcholinesterase
      (plasmacholinesterase). Multiple variants of this enzyme are known (A, F, S, H,
      J, K variants) with different effects on enzyme activity. This study was
      undertaken to evaluate the use of molecular genetic methods in patients with
      clinically prolonged neuromuscular block. METHODS: Nine patients with a
      neuromuscular block of 14 min to 5 h were selected. All four exons of the
      butyrylcholinesterase were amplified by polymerase chain reaction and analyzed by
      automated sequencing. Molecular genetic results were compared with clinical
      relaxation time and with biochemical test results (total butyrylcholinesterase
      activity, dibucaine and fluoride inhibition). RESULTS: Seven of nine patients
      were mutation carriers. Five of these had more than one mutation. The A and K
      variants were the most frequent variations. Three of four patients who were
      homozygous for the A variant were also carriers of the K allele. The authors
      identified one novel mutation (G1294T) introducing a stop codon at amino acid
      position 432. The duration of neuromuscular block was substantially different
      between patients with identical butyrylcholinesterase genotypes. CONCLUSIONS:
      Variations in the genetic sequence of butyrylcholinesterase are frequent in
      patients with prolonged duration of action of succinylcholine. Direct sequencing
      of the whole butyrylcholinesterase gene is an appropriate method for genotyping
      and, accordingly, should be used in future clinical studies with drugs
      metabolized by this enzyme (e.g., succinylcholine, mivacurium).

PMID- 15731590
TI  - Effect of alpha2B-adrenoceptor polymorphism on peripheral vasoconstriction in
      healthy volunteers.
AB  - BACKGROUND: Alpha-2B adrenoceptor is the vasoconstrictive subtype in the mouse.
      Human alpha2B-AR deletion (D) allele has been associated with loss of short-term
      agonist-promoted receptor desensitization, which may lead to increased
      vasoconstriction on alpha2 activation. The goal of this study was to test the
      hypothesis that alpha2B-adrenoceptor activation induces enhanced vasoconstriction
      in carriers of the DD genotype, compared with carriers of the insertion/insertion
      (II) genotype. METHODS: The authors administered increasing doses of
      dexmedetomidine (targeting plasma concentrations of 0.15, 0.3, 0.6, and 1.2
      ng/ml) to 16 healthy young volunteers (8 carrying the alpha2B DD genotype, 8
      carrying the II genotype) in whom sympatholytic effects of the drug were
      attenuated by general anesthesia. Measurements were made of finger blood volume
      (an indicator of vasoconstriction) by photoplethysmographic determination of
      light transmitted through a finger, finger blood flow by venous occlusion
      plethysmography, and hemodynamic variables. RESULTS: All concentration of
      dexmedetomidine increased light transmitted through the finger (vasoconstriction)
      and systolic blood pressure and decreased heart rate in both groups (P < 0.001
      for all). Dexmedetomidine reduced finger arterial inflow only in the DD group (P
      < 0.001). Dexmedetomidine had no effect on finger venous outflow or venous
      capacitance. There were no significant differences between the II and DD groups
      in any of the variables. CONCLUSIONS: The results of this study confirm the
      alpha2 agonist induced vasomotor and hemodynamic effects in peripheral
      vasculature. However, the results do not support the hypothesis that alpha2B
      adrenoceptor polymorphism has an effect on peripheral vasoconstriction in humans.

PMID- 15731591
TI  - The impact of pharmacogenomics on postoperative nausea and vomiting: do CYP2D6
      allele copy number and polymorphisms affect the success or failure of ondansetron
      prophylaxis?
AB  - BACKGROUND: Some patients treated with ondansetron for postoperative nausea and
      vomiting do not respond to therapy. One possible mechanism for this failure is
      ultrarapid drug metabolism via the cytochrome P-450 system, specifically the
      enzyme 2D6 (CYP2D6). Ultrarapid metabolism is seen in patients with multiple
      functional copies (>/= 3) of the CYP2D6 allele. This study was designed to
      determine whether patients who were given prophylactic ondansetron and had
      multiple CYP2D6 alleles had an increased rate of postoperative nausea and
      vomiting. METHODS: Two hundred fifty female patients undergoing standardized
      general anesthesia were given 4 mg ondansetron 30 min before extubation. Patients
      were observed for symptoms of nausea and vomiting. DNA was extracted from blood
      in all patients and was analyzed by using a gene-specific probe to determine the
      CYP2D6 gene copy number and genotyped by polymerase chain reaction amplification
      with a custom oligonucleotide microarray to determine the specific CYP2D6
      genotypes. RESULTS: Eighty-eight patients experienced nausea, and 37 of those
      patients also had vomiting. In patients with one, two, or three CYP2D6 copies,
      the incidences of vomiting were 3 in 33 (27%), 27 in 198 (14%), and 7 in 23
      (30%), respectively. The incidence of vomiting in subjects with three CYP2D6
      copies was significantly different from those with two copies, but not from those
      with one copy. When analyzed by genotype, the incidences of vomiting in poor,
      intermediate, extensive, and ultrarapid metabolizers were 1 in 12 (8%), 5 in 30
      (17%), 26 in 176 (15%), and 5 in 11 (45%), respectively (P < 0.01 vs. all other
      groups). There were no differences between groups in the incidence of nausea
      based on CYP2D6 copy number or genotype. CONCLUSIONS: Patients with three copies
      of the CYP2D6 gene, a genotype consistent with ultrarapid metabolism, or both
      have an increased incidence of ondansetron failure for the prevention of
      postoperative vomiting but not nausea.

PMID- 15731592
TI  - Pharmacogenetic determinants of human liver microsomal alfentanil metabolism and
      the role of cytochrome P450 3A5.
AB  - BACKGROUND: There is considerable unexplained interindividual variability in the
      clearance of alfentanil. Alfentanil undergoes extensive metabolism by cytochrome
      P4503A4 (CYP3A4). CYP3A5 is structurally similar to CYP3A4 and metabolizes most
      CYP3A4 substrates but is polymorphically expressed. Livers with the CYP3A5*1
      allele contain higher amounts of the native CYP3A5 protein than livers homozygous
      for the mutant CYP3A5*3 allele. This investigation tested the hypothesis that
      alfentanil is a substrate for CYP3A5 and that CYP3A5 pharmacogenetic variability
      influences human liver alfentanil metabolism. METHODS: Alfentanil metabolism to
      noralfentanil and N-phenylpropionamide was determined in microsomes from two
      groups of human livers, characterized for CYP3A4 and CYP3A5 protein content: low
      CYP3A5 (2.0-5.2% of total CYP3A, n = 10) and high CYP3A5 (46-76% of total CYP3A,
      n = 10). Mean CYP3A4 content was the same in both groups. The effects of the
      CYP3A inhibitors troleandomycin and ketoconazole, the latter being more potent
      toward CYP3A4, on alfentanil metabolism were also determined. RESULTS: In the low
      versus high CYP3A5 livers, respectively, noralfentanil formation was 77 +/- 31
      versus 255 +/- 170 pmol . min . mg, N-phenylpropionamide formation was 8.0 +/-
      3.1 versus 20.5 +/- 14.0 pmol . min . mg, and the metabolite ratio was 9.5 +/-
      0.4 versus 12.7 +/- 1.4 (P < 0.05 for all). There was a poor correlation between
      alfentanil metabolism and CYP3A4 content but an excellent correlation when CYP3A5
      (i.e., total CYP3A content) was considered (r = 0.81, P < 0.0001). Troleandomycin
      inhibited alfentanil metabolism similarly in the low and high CYP3A5 livers;
      ketoconazole inhibition was less in the high CYP3A5 livers. CONCLUSION: In
      microsomes from human livers expressing the CYP3A5*1 allele and containing higher
      amounts of CYP3A5 protein, compared with those with the CYP3A5*3 allele and
      little CYP3A5, there was greater alfentanil metabolism, metabolite ratios more
      closely resembled those for expressed CYP3A5, and inhibitors with differing
      CYP3A4 and CYP3A5 selectivities had effects resembling those for expressed
      CYP3A5. Therefore, alfentanil is metabolized by human liver microsomal CYP3A5 in
      addition to CYP3A4, and pharmacogenetic variability in CYP3A5 expression
      significantly influences human liver alfentanil metabolism in vitro. Further
      investigation is warranted to assess whether the CYP3A5 polymorphism is a factor
      in the interindividual variability of alfentanil metabolism and clearance in
      vivo.

PMID- 15731593
TI  - Effect of N-methyl-D-aspartate receptor epsilon1 subunit gene disruption of the
      action of general anesthetic drugs in mice.
AB  - BACKGROUND: Recent molecular strategies demonstrated that the N-methyl-d
      aspartate (NMDA) receptor is a major target site of anesthetic agents. In a
      previous article, the authors showed that knocking out the NMDA receptor epsilon1
      subunit gene markedly reduced the hypnotic effect of ketamine in mice. In the
      current study, the authors examined the in vivo contribution of the NMDA receptor
      epsilon1 subunit to the action of other anesthetic drugs. METHODS: The authors
      determined the anesthetic effects of nitrous oxide on sevoflurane potency in NMDA
      receptor epsilon1 subunit knockout mice compared with those in wild-type mice.
      They then tested the hypnotic effect of gamma-aminobutyric acid-mediated agents,
      such as propofol, pentobarbital, diazepam, and midazolam, in knockout mice and
      wild-type mice. RESULTS: The anesthetic action of sevoflurane itself was
      unaffected by the abrogation of the NMDA receptor epsilon1 subunit. Adding
      nitrous oxide reduced the required concentration of sevoflurane to induce
      anesthesia in wild-type mice, whereas this sparing effect was diminished in
      knockout mice. Furthermore, propofol, pentobarbital, diazepam, and midazolam also
      had markedly attenuated effects in knockout mice. CONCLUSIONS: Although it has
      been demonstrated that knocking out the expression of receptors may induce
      changes in the composition of the subunits, the network circuitry, or both, the
      current findings show consistently that the NMDA receptor epsilon1 subunit
      mediates nitrous oxide but not sevoflurane anesthesia. Furthermore, the
      attenuated anesthetic impact of propofol, pentobarbital, diazepam, and midazolam
      as well as ketamine in knockout mice suggests that the NMDA receptor epsilon1
      subunit could be indirectly involved in the hypnotic action of these drugs in
      vivo.

PMID- 15731594
TI  - Awakening concentration of desflurane is decreased in patients with obstructive
      jaundice.
AB  - BACKGROUND: Some studies suggest that behavioral complications of cholestasis,
      such as fatigue and pruritus, may be associated with altered neurotransmission in
      the brain. Because inhaled anesthetics primarily act on ion channels and
      receptors on the neuronal cell membrane and alter synaptic transmission in the
      central nervous system, it is possible that altered sensitivity to inhaled
      anesthetics may occur in cholestatic patients. Therefore, the authors compared
      the minimum alveolar concentration (MAC)-awake of desflurane in obstructive
      jaundiced patients with the MACawake in nonjaundiced patients. METHODS: Patients
      underwent inhalational induction of anesthesia with desflurane. MACawake was
      determined in each patient by observing the response to a verbal command (open
      eyes on request). An end-tidal anesthetic concentration was maintained at an
      initial target level of 1.4% for 15 min before a command. If a positive response
      was observed, the concentration of desflurane was increased by 0.1% and again
      kept constant for 15 min. The verbal command was then continued. This process was
      repeated until an end-tidal concentration was reached at which the patient did
      not respond to command. The anesthetic concentration midway between the value
      permitting the response and that just preventing the response was defined as
      MACawake for each patient. RESULTS: The MACawake of desflurane for patients with
      obstructive jaundice (1.78 +/- 0.19%) was significantly less than those observed
      for the control group (2.17 +/- 0.25%; P < 0.001) and correlated significantly
      with serum total bilirubin (r = -0.67, P = 0.0004). CONCLUSIONS: The MACawake of
      desflurane is reduced in obstructive jaundiced patients compared with
      nonjaundiced controls.

PMID- 15731595
TI  - Effects of bispectral index monitoring on recovery from surgical anesthesia in
      1,580 inpatients from an academic medical center.
AB  - BACKGROUND: The purpose of this study was to determine whether monitoring
      Bispectral Index (BIS) would affect recovery parameters in patients undergoing
      inpatient surgery. METHODS: Anesthesia providers (n = 69) were randomly assigned
      to one of two groups, a BIS or non-BIS control group. A randomized crossover
      design was used, with reassignment at monthly intervals for 7 months. Duration of
      time in the postanesthesia care unit, time from the end of surgery to leaving the
      operating room, and incidence of delayed recovery (> 50 min in recovery) were
      compared in patients treated intraoperatively with or without BIS monitoring.
      Data were analyzed by analysis of variance, unpaired t test, or chi-square test
      as appropriate. RESULTS: One thousand five hundred eighty patients in an academic
      medical center were studied. The mean BIS in the monitored group was 47. No
      differences were found in recovery parameters between the BIS-monitored group and
      the control group when comparisons were made using all subjects or when data were
      analyzed within anesthetic subgroups stratified by anesthetic agent or duration
      of anesthesia. There were some small reductions in the intraoperative
      concentration of sevoflurane (but not isoflurane). CONCLUSIONS: The use of BIS
      monitoring for inpatients undergoing a wide variety of surgical procedures in an
      academic medical center had some minor effects on intraoperative anesthetic use
      but had no impact on recovery parameters.

PMID- 15731596
TI  - Increased pulmonary venous resistance contributes to increased pulmonary artery
      diastolic-pulmonary wedge pressure gradient in acute respiratory distress
      syndrome.
AB  - BACKGROUND: Pulmonary artery diastolic (PAD)-pulmonary wedge pressure (PWP)
      gradient has been shown to be increased in sepsis and acute respiratory distress
      syndrome (ARDS). Because pulmonary venous vasoconstriction induced by endotoxemia
      in sepsis or postcapillary leukocyte aggregation in ARDS or both can increase
      pulmonary venous resistance (Rpv), it is possible that the elevated Rpv increases
      PAD-PWP. The authors examined this possibility by assessing the correlation
      between Rpv and PAD-PWP gradient in patients with ARDS. METHODS: Included were 20
      patients with ARDS who required surgical procedures during general anesthesia.
      Rpv was calculated as the difference between mean pulmonary artery (PA) output
      pressure and PWP divided by cardiac index. Mean PA output pressure was computed
      from harmonic form of the recorded PA pressure by applying an attenuating factor
      to its phasic components, for which Fourier analysis was used. Total pulmonary
      vascular resistance (TPVR) was calculated as the difference between mean PA input
      pressure and PWP divided by cardiac index. To avoid the effect of PA resistance
      on TPVR and Rpv, the relative pulmonary venous resistance (Rpv/TPVR) was used.
      RESULTS: There was a good correlation between Rpv/TPVR and PAD-PWP gradient (R =
      0.698, P < 0.0001). When patients were classified into two groups based on PAD
      PWP gradient, the Rpv/TPVR was 0.66 +/- 0.06 in the group with a PAD-PWP gradient
      of 6 mmHg or greater and 0.46 +/- 0.08 in the other group (P < 0.0001).
      CONCLUSION: A strong correlation between Rpv/TPVR and PAD-PWP gradient suggests
      that the increased Rpv contributes to increased PAD-PWP gradient in patients with
      ARDS.

PMID- 15731597
TI  - Inhibitory effects of lidocaine and mexiletine on vasorelaxation mediated by
      adenosine triphosphate-sensitive K+ channels and the role of kinases in the
      porcine coronary artery.
AB  - BACKGROUND: Effects of antiarrhythmic drugs on coronary vasodilation mediated by
      K channels have not been studied. Modulator roles of protein kinase C and
      tyrosine kinase in the activity of K channels have also been unclear in the
      coronary artery. The current study examined whether lidocaine and mexiletine in
      the porcine coronary artery modify the vasorelaxation mediated by adenosine
      triphosphate-sensitive K channels via activation of protein kinase C and tyrosine
      kinase. METHODS: Porcine coronary arteries without endothelium were suspended for
      isometric force recording, and vasorelaxation to levcromakalim (10 to 10 m) was
      obtained. Changes in membrane potentials produced by levcromakalim (10 m) were
      also recorded. RESULTS: Glibenclamide completely abolished vasorelaxation as well
      as hyperpolarization in response to levcromakalim. Lidocaine and mexiletine
      significantly reduced these responses. Calphostin C, Go 6976, genistein, and
      erbstatin A partly restored vasorelaxation or hyperpolarization in response to
      levcromakalim in arteries treated with mexiletine but not in those with
      lidocaine, whereas these inhibitors did not alter the vasorelaxation to
      levcromakalim. Phorbol 12-myristate 13-acetate produced reduction of
      vasorelaxation in response to levcromakalim, which is recovered by calphostin C
      or Go 6976. CONCLUSIONS: Therefore, lidocaine and mexiletine inhibit
      vasorelaxation mediated by the activation of adenosine triphosphate-sensitive K
      channels in the coronary artery. Protein kinase C and tyrosine kinase seem to
      have roles in the inhibitory effect of mexiletine but not in that of lidocaine.
      Class Ib antiarrhythmic drugs may reduce coronary vasodilation mediated by
      adenosine triphosphate-sensitive K channels via the differential modulator
      effects on these kinases.

PMID- 15731598
TI  - Ketamine attenuates acetylcholine-induced contraction by decreasing myofilament
      Ca2+ sensitivity in pulmonary veins.
AB  - BACKGROUND: The authors investigated the extent and cellular mechanisms by which
      the intravenous anesthetic ketamine alters acetylcholine-induced contraction in
      pulmonary veins (PVs). They tested the hypothesis that ketamine inhibits
      acetylcholine contraction in PVs. METHODS: Canine PV rings with endothelium (E+)
      and without endothelium (E-) were isolated for measurement of isometric tension.
      The effects of ketamine (10(-5) m approximately 10(-3) m) on acetylcholine
      contraction were assessed in E+ and E- rings. The effects of inhibiting nitric
      oxide synthase on ketamine-induced changes in acetylcholine contraction were
      investigated in E+ rings, whereas the effects of Ca2+ influx and Ca2+ release
      were investigated in E- rings. In fura-2 loaded E- PV strips, the effects of
      ketamine (10(-4) m) on the intracellular Ca2+ concentration-tension relation
      (i.e., myofilament Ca sensitivity) were assessed in the presence or absence of
      acetylcholine. The roles of the protein kinase C and rho-kinase signaling
      pathways in ketamine-induced changes in myofilament Ca2+ sensitivity were also
      investigated. RESULTS: Ketamine caused dose-dependent (P < 0.001) inhibition of
      acetylcholine contraction in E+ and E- PV rings. The ketamine-induced attenuation
      of acetylcholine contraction was still observed after inhibition of nitric oxide
      synthase (P = 0.002), Ca2+ influx (P < 0.001), and Ca2+ release (P = 0.021).
      Ketamine alone had no effect on myofilament Ca2+ sensitivity (P = 0.892) but
      attenuated (P = 0.038) the acetylcholine-induced increase in myofilament Ca2+
      sensitivity. This attenuation was still observed after rho-kinase inhibition (P =
      0.039), whereas it was abolished by protein kinase C inhibition (P = 0.798).
      CONCLUSIONS: Ketamine attenuates acetylcholine contraction by inhibiting the
      acetylcholine-induced increase in myofilament Ca2+ sensitivity, which is mediated
      by the protein kinase C signaling pathway.

PMID- 15731599
TI  - Vaporized perfluorohexane attenuates ventilator-induced lung injury in isolated,
      perfused rabbit lungs.
AB  - BACKGROUND: The authors tested the hypothesis that administration of vaporized
      perfluorohexane may attenuate ventilator-induced lung injury. METHODS: In
      isolated, perfused rabbit lungs, airway pressure-versus-time curves were
      recorded. At baseline, peak inspiratory pressure and positive end-expiratory
      pressure of mechanically ventilated lungs were set to obtain straight pressure
      versus-time curves in both the lower and upper ranges, which are associated with
      less collapse and overdistension, respectively. After that, peak inspiratory
      pressure and positive end-expiratory pressure were set at 30 cm H2O and 0,
      respectively, and animals were randomly assigned to one of two groups: (1)
      simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and
      (2) control group-ventilation with room air (n = 7). After 20 min of cycling
      collapse and overdistension, tidal volume and positive end-expiratory pressure
      were set back to baseline levels, administration of perfluorohexane in the
      therapy group was stopped, and mechanical ventilation was continued for up to 60
      min. Lung weight, mean pulmonary artery pressure, and concentration of
      thromboxane B2 in the perfusate were measured. In addition, the distribution of
      pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres.
      RESULTS: Significantly higher peak inspiratory values developed in control lungs
      than in lungs treated with perfluorohexane. In addition, upper ranges of pressure
      versus-time curves were closer to straight lines in the perfluorohexane group.
      Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were
      significantly higher in controls than in perfluorohexane-treated lungs. Also,
      redistribution of pulmonary perfusate flow from caudal to cranial zones was less
      important in the treatment group. CONCLUSION: The authors conclude that the
      administration of perfluorohexane vapor attenuates the development of ventilator
      induced lung injury in isolated, perfused rabbit lungs.

PMID- 15731600
TI  - Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves
      increases in intracellular Ca2+ and mitogen-activated protein kinases.
AB  - BACKGROUND: The volatile anesthetic isoflurane reduces acute and delayed neuron
      death in vitro models of brain ischemia, an action that the authors hypothesize
      is related to moderate increases in intracellular calcium concentration
      ([Ca2+]i). Specifically, the authors propose that during hypoxia, moderate
      increases in [Ca2+]i in the presence of isoflurane stimulates the Ca2+-dependent
      phosphorylation of members of the mitogen-activated protein kinase (MAP) kinase
      Ras-Raf-MEK-ERK pathway that are critical for neuroprotective signaling and
      suppression of apoptosis. METHODS: Death of CA1, CA3, and dentate neurons in rat
      hippocampal slice cultures was assessed by propidium iodide fluorescence 48-72 h
      after 60-75 min of hypoxia. [Ca2+]i in CA1 neurons was measured with fura-2 and
      fura-2 FF. Concentrations of the survival-signaling proteins Ras, MEK, MAP kinase
      p42/44, and protein kinase B (Akt) were assessed by immunostaining, and specific
      inhibitors were used to ascertain the role of Ca2+ and MAP kinases in mediating
      survival. RESULTS: Isoflurane, 1%, decreased neuron death in CA1, CA3, and
      dentate gyrus neurons after 60 but not 75 min of hypoxia. Survival of CA1 neurons
      required an inositol triphosphate receptor-dependent increase in [Ca2+]i of 30
      100 nm that activated the Ras-Raf-MEK-ERK (p44/42) signaling pathway. Isoflurane
      also increased the phosphorylation of Akt during hypoxia. CONCLUSIONS: Isoflurane
      stimulates the phosphorylation of survival signaling proteins in hypoxic neurons.
      The mechanism involves a moderate increase in [Ca2+]i from release of Ca from
      inositol triphosphate receptor-dependent intracellular stores. The increase in
      [Ca2+]i sets in motion signaling via Ras and the MAP kinase p42/44 pathway and
      the antiapoptotic factor Akt. Isoflurane neuroprotection thus involves
      intracellular signaling well known to suppress both excitotoxic and
      apoptotic/delayed cell death.

PMID- 15731601
TI  - Facilitation of serotonergic activity and amnesia in rats caused by intravenous
      anesthetics.
AB  - BACKGROUND: Midazolam and propofol often provoke retrograde amnesia after
      recovery from anesthesia in humans. Because an increase in central serotonergic
      activity impairs learning and memory, the authors examined the relation between
      changes in the serotonergic activity caused by intravenous anesthetics and
      memory. METHODS: Changes in extracellular concentrations of monoamines and their
      metabolites were investigated in rat striatum by a microdialysis procedure, and
      the effects of intraperitoneal injections of midazolam (5 mg/kg), propofol (60
      mg/kg), and pentobarbital (15 mg/kg) were then examined. To evaluate the
      behavioral alteration with these agents, the authors used a step-through passive
      avoidance test. RESULTS: Midazolam and propofol slightly increased the
      extracellular concentration of 5-hydroxytryptamine in the striatum, although
      pentobarbital did not produce any changes. Midazolam and propofol increased the
      extracellular concentration of 5-hydroxyindoleacetic acid, a metabolite of 5
      hydroxytryptamine, with the peak values each 138% and 138% of that in saline
      injected animals, respectively. However, pentobarbital decreased the 5
      hydroxyindoleacetic acid concentration to 61% of that in the saline group.
      Administration of midazolam or propofol immediately after the completing the
      passive avoidance learning reduced step-through latencies after 24 h, although
      pentobarbital-injected animals maintained a consistent performance. The effects
      of midazolam and propofol on step-through latencies were completely antagonized
      by intracerebroventricular administration of spiroxatrine (5 microg), a 5
      hydroxytryptamine 1A antagonist, 30 min before training. CONCLUSIONS: Midazolam
      and propofol increased central serotonergic activity and provoked retrograde
      amnesia. Because amnesia was completely diminished by a 5-hydroxytryptamine
      antagonist, facilitation of the serotonergic system may be involved in retrograde
      amnesia caused by these agents.

PMID- 15731602
TI  - Drastic decrease in isoflurane minimum alveolar concentration and limb movement
      forces after thoracic spinal cooling and chronic spinal transection in rats.
AB  - BACKGROUND: Individuals with spinal cord injury may undergo multiple surgical
      procedures; however, it is not clear how spinal cord injury affects anesthetic
      requirements and movement force under anesthesia during both acute and chronic
      stages of the injury. METHODS: The authors determined the isoflurane minimum
      alveolar concentration (MAC) necessary to block movement in response to
      supramaximal noxious stimulation, as well as tail-flick and hind paw withdrawal
      latencies, before and up to 28 days after thoracic spinal transection. Tail-flick
      and hind paw withdrawal latencies were measured in the awake state to test for
      the presence of spinal shock or hyperreflexia. The authors measured limb forces
      elicited by noxious mechanical stimulation of a paw or the tail at 28 days after
      transection. Limb force experiments were also conducted in other animals that
      received a reversible spinal conduction block by cooling the spinal cord at the
      level of the eighth thoracic vertebra. RESULTS: A large decrease in MAC (to </=
      40% of pretransection values) occurred after spinal transection, with partial
      recovery (to approximately 60% of control) at 14-28 days after transection. Awake
      tail-flick and hind paw withdrawal latencies were facilitated or unchanged,
      whereas reflex latencies under isoflurane were depressed or absent. However, at
      80-90% of MAC, noxious stimulation of the hind paw elicited ipsilateral limb
      withdrawals in all animals. Hind limb forces were reduced (by >/= 90%) in both
      chronic and acute cold-block spinal animals. CONCLUSIONS: The immobilizing
      potency of isoflurane increases substantially after spinal transection, despite
      the absence of a baseline motor depression, or "spinal shock." Therefore,
      isoflurane MAC is determined by a spinal depressant action, possibly counteracted
      by a supraspinal facilitatory action. The partial recovery in MAC at later time
      points suggests that neuronal plasticity after spinal cord injury influences
      anesthetic requirements.

PMID- 15731603
TI  - Comparison of the different approaches to saphenous nerve block.
AB  - BACKGROUND: The authors compared the efficacy of the different approaches to
      saphenous nerve block. METHODS: The following approaches to saphenous nerve block
      were compared in 10 volunteers: perifemoral, transsartorial, block at the medial
      femoral condyle, below-the-knee field block, and blockade at the level of the
      medial malleolus. Each volunteer underwent all five blocks, and the interval
      between blocks was 3-7 days. The sequence of injection was randomized by Latin
      square design. Sensory blockade at the medial aspects of the leg and foot and the
      strength of the anterior thigh muscles were noted. RESULTS: The transsartorial,
      perifemoral, and below-the-knee field block approaches were more effective than
      block at the medial femoral condyle in providing sensory anesthesia to the medial
      aspect of the leg. The transsartorial approach was more effective than block at
      the medial femoral condyle and below-the-knee field block in providing sensory
      anesthesia to the medial aspect of the foot. Compared with the perifemoral
      approach, the transsartorial approach did not cause weakness of the hip flexors
      and the knee extensors. In volunteers with partial numbness in the medial aspect
      of the foot, supplemental block of the medial dorsal cutaneous branch of the
      superficial peroneal nerve resulted in complete sensory blockade. CONCLUSIONS:
      Sensory blockade in the medial aspects of the leg and foot is best achieved with
      the transsartorial approach. In some subjects, supplementary block of the medial
      dorsal cutaneous branch of the superficial peroneal nerve may have to be
      performed to assure complete numbness of the medial aspect of the foot.

PMID- 15731604
TI  - Variability of target-controlled infusion is less than the variability after
      bolus injection.
AB  - BACKGROUND: Target-controlled infusion (TCI) drug delivery systems deliver
      intravenous drugs based on pharmacokinetic models. TCI devices administer a
      bolus, followed by exponentially declining infusions, to rapidly achieve and
      maintain pseudo-steady state drug concentrations in the plasma or at the site of
      drug effect. Many studies have documented the prediction accuracy of TCI devices.
      The authors' goal was to apply linear systems theory to characterize the relation
      between the variability in concentrations achieved with TCI devices and the
      variability in concentrations after intravenous bolus injection. METHODS: The
      authors developed a mathematical model of the variability of any arbitrary method
      of drug delivery, based on the variability with intravenous bolus injection or
      the variability with an arbitrary infusion regimen. They tested the model in a
      simulation of 1,000 patients receiving propofol by simple bolus injection,
      conventional infusion, or a TCI device. The authors then examined an experimental
      data set for the same behavior. RESULTS: The variability of any arbitrary
      infusion regimen, including TCI, is bounded by the variability after bolus
      injection. This is observed in the simulation and experimental data sets as well.
      CONCLUSION: TCI devices neither create nor eliminate biologic variability. For
      any drug described by linear pharmacokinetic models, no infusion regimen,
      including TCI, can have higher variability than that observed after bolus
      injection. The median performance of TCI devices should be reasonably close to
      the prediction of the device. However, the overall spread of the observations is
      an intrinsic property of the drug, not the TCI delivery system.

PMID- 15731605
TI  - Minimum local analgesic doses of ropivacaine, levobupivacaine, and bupivacaine
      for intrathecal labor analgesia.
AB  - BACKGROUND: Doses for intrathecal opioid-local anesthetic mixtures have been
      arbitrarily chosen. The aim of this study was to compare the analgesic efficacies
      of intrathecal ropivacaine, levobupivacaine, and bupivacaine for labor analgesia
      and to determine the analgesic potency ratios for these three drugs. For this
      purpose, the authors used the up-down sequential allocation model, which
      estimates the minimum local analgesic dose for intrathecal local anesthetic.
      METHODS: Ninety-seven nulliparous term parturients in spontaneous labor,
      requesting combined spinal-epidural analgesia, were randomly allocated to one of
      three groups to receive 0.25% spinal ropivacaine, levobupivacaine, or
      bupivacaine. The initial dose of the local anesthetic drug was chosen to be 2.5
      mg, and the testing interval was set at 0.25 mg. The subsequent doses were
      determined by the response of the previous parturient. Efficacy was accepted if
      the visual analog pain score decreased to 10 mm or less on a 100-mm scale within
      30 min. The minimum local analgesic dose was calculated using the method of Dixon
      and Massey. RESULTS: The intrathecal minimum local analgesic dose was 3.64 mg
      (95% confidence interval, 3.33-3.96 mg) for ropivacaine, 2.94 (2.73-3.16) mg for
      levobupivacaine, and 2.37 (2.17-2.58) mg for bupivacaine. The relative analgesic
      potency ratios were 0.65 (0.56-0.76) for ropivacaine:bupivacaine, 0.80 (0.70
      0.92) for ropivacaine:levobupivacaine, and 0.81 (0.69-0.94) for
      levobupivacaine:bupivacaine. There were significant trends (P </= 0.021) for
      greater motor block with bupivacaine and levobupivacaine. CONCLUSIONS: This study
      suggests a potency hierarchy of spinal bupivacaine > levobupivacaine >
      ropivacaine.

PMID- 15731606
TI  - A comparison of median effective doses of intrathecal levobupivacaine and
      ropivacaine for labor analgesia.
AB  - BACKGROUND: The study was designed to determine and compare the median effective
      doses (MEDs) of intrathecal ropivacaine with levobupivacaine for labor analgesia.
      METHODS: In this double-blind study, 100 parturients in early labor were
      randomized to receive either intrathecal ropivacaine or levobupivacaine. For each
      drug, the patients were assigned to receive one of the five doses studied, namely
      1, 1.5, 2, 2.5, or 3 mg. Effective analgesia was defined as a pain score (0-100
      visual analog scale) of less than 10 within 15 min of injection, lasting for 45
      min or more after the induction of analgesia. MEDs were derived from probit
      analysis. The duration of analgesia rendered by the two drugs at 2.5 and 3 mg was
      also compared. RESULTS: The MED for levobupivacaine was 1.07 mg (95% confidence
      interval, 0.88-1.25 mg), and the MED for ropivacaine was 1.40 mg (95% confidence
      interval, 1.20-1.61 mg). Levobupivacaine was found to be 1.31 (95% confidence
      interval, 1.04-2.01) times more potent than ropivacaine. At doses of 2.5 mg or
      greater, there was no significant difference in duration of analgesia between
      levobupivacaine (median, 63.5 min; range, 46-123 min) and ropivacaine (median,
      59.0 min; range, 47-93 min; P = 0.18). We detected no difference in the incidence
      of hypotension, nausea and vomiting, motor block, or abnormal fetal heart tracing
      between the two drugs. CONCLUSIONS: The MED of intrathecal ropivacaine for labor
      analgesia was significantly greater than levobupivacaine experimentally, but this
      significance was reduced when the comparison was based on molar potency. There
      was no difference in the duration of analgesia or adverse effects between the two
      drugs at higher doses (2.5 mg or greater).

PMID- 15731607
TI  - alpha2-Adrenoceptor activation by clonidine enhances stimulation-evoked
      acetylcholine release from spinal cord tissue after nerve ligation in rats.
AB  - BACKGROUND: Spinally administered clonidine produces analgesia via alpha2
      adrenergic receptors. The analgesic potency of clonidine and its dependency on
      muscarinic acetylcholine receptors increase in rats after nerve injury. The
      authors hypothesized that these changes reflect greater acetylcholine release
      from the spinal cord by clonidine, either through direct or indirect effects.
      METHODS: Male Sprague-Dawley rats were divided into two groups: no surgery or
      left L5 and L6 spinal nerve ligation (SNL). All experiments were performed 3
      weeks after SNL. Crude synaptosomes were prepared from the spinal enlargement and
      loaded with [H]choline. Samples were incubated with clonidine in the absence or
      presence of KCl depolarization. The authors also examined the effect of clonidine
      on KCl evoked acetylcholine release using perfusion of spinal cord slices, in
      which some spinal circuitry is maintained. RESULTS: In synaptosomes, clonidine
      alone induced minimal acetylcholine release, which was actually greater in tissue
      from normal rats than in tissue from SNL rats. In the presence of KCl
      depolarization, however, clonidine enhanced acetylcholine release in tissue from
      SNL rats but inhibited release in tissue from normal rats. Similarly, in spinal
      cord slices, clonidine enhanced KCl evoked acetylcholine release in tissue from
      SNL animals but inhibited such release in tissue from normal animals. The alpha2
      adrenoceptor antagonist idazoxan inhibited the effects of clonidine in slices
      from SNL rats. CONCLUSION: These results suggest that clonidine enhances
      depolarization-induced acetylcholine release in neuropathic but not in normal
      spinal cord tissue. Interestingly, this enhanced acetylcholine release by
      clonidine occurs in a synaptosomal preparation, consistent with a direct effect
      on alpha2 adrenoceptors on cholinergic terminals. Enhanced release of
      acetylcholine by clonidine could contribute to increased analgesia of clonidine
      in neuropathic pain.

PMID- 15731609
TI  - Gerard W. Ostheimer "What's New in Obstetric Anesthesia" Lecture.

PMID- 15731608
TI  - Pharmacogenetics of anesthetic and analgesic agents.
AB  - Predicting a patient's response to a particular drug has long been a goal of
      clinicians. Rapid advances in molecular biology have enabled researchers to
      identify associations between an individual's genetic profile and drug response.
      Pharmacogenetics is the study of the molecular mechanisms that underlie
      individual differences in drug metabolism, efficacy, and side effects. The
      pharmacogenetics of commonly used anesthetic and analgesic agents are reviewed.

PMID- 15731610
TI  - Cervical spine considerations when anesthetizing patients with Down syndrome.

PMID- 15731611
TI  - Intrathecal catheter tip inflammatory mass: a failure of clonidine to protect.

PMID- 15731612
TI  - Diaphragmatic paralysis after endovascular stent grafting of a thoracoabdominal
      aortic aneurysm.

PMID- 15731614
TI  - Disadvantages of ultrasound guidance in caudal epidural needle placement.

PMID- 15731615
TI  - Ultrasound-guided caudal epidural injection.

PMID- 15731616
TI  - Anesthesia for outpatient surgery: how fast is fast?

PMID- 15731617
TI  - In clinical practice, coadministration of sevoflurane or propofol could
      antagonize remifentanil stimulation of N-methyl-D-aspartate receptors.

PMID- 15731619
TI  - CobraPLA is the perilaryngeal airway.

PMID- 15731625
TI  - Cardioprotective properties of sevoflurane in patients undergoing coronary
      surgery with cardiopulmonary bypass are related to the modalities of its
      administration.

PMID- 15731621
TI  - Metabolic acidosis due to propofol infusion.

PMID- 15731628
TI  - Tolerance to miotic effects of opioids.

PMID- 15731627
TI  - Epidural hematoma after epidural steroid injection in a patient withholding
      enoxaparin per guidelines.

PMID- 15731629
TI  - Potentially dangerous fracture of the needleless interlink vial access cannula.

PMID- 15731635
TI  - Building bridges...and strengthening nursing.
AB  - In light of current nursing employment trends, nurses and employment specialists
      in one rural northern Iowa healthcare organization are collaborating to retain
      and recruit nurses. The purpose of this article is to describe how these
      individuals worked toward a comprehensive, cohesive approach to the development,
      implementation, and evaluation of learning opportunities that support these
      efforts. Staff development educators played key roles in developing program
      purposes, descriptions, curriculum, and outcome measures.

PMID- 15731636
TI  - Writing better test items.
AB  - Professional development specialists have had little opportunity to learn how to
      write test items to meet the expectations of today's graduate nurse. Schools of
      nursing have moved away from knowledge-level test items and have had to develop
      more application and analysis items to prepare graduates for the National Council
      Licensure Examination (NCLEX). This same type of question can be used effectively
      to support a competence assessment system and document critical thinking skills.

PMID- 15731637
TI  - The impact of team building on communication and job satisfaction of nursing
      staff.
AB  - A series of team-building activities were conducted on a medical-surgical unit
      and their impact on staff's communication and job satisfaction was examined.
      Forty-four unit personnel participated in the interventions. Staff communication
      and job satisfaction were measured before and after the intervention. The
      findings linked team-building activities with improved staff communication and
      job satisfaction. Team-building strategies assisted the nurse leader/manager to
      build an effective work team by strengthening communication and interpersonal
      relationships so that the staff could function as a more cohesive group. Staff
      development consultants can help nurse managers become more effective team
      leaders by identifying the necessary resources and by helping to plan and
      coordinate team-building strategies.

PMID- 15731639
TI  - Nurses' death anxiety, comfort level during communication with patients and
      families regarding death, and exposure to communication education: a quantitative
      study.
AB  - The first purpose of this study was to determine if a nurse's death anxiety is
      related to the comfort level of the nurse during communication with patients and
      families regarding death. The second purpose was to explore whether nurses
      reported having been exposed to communication education regarding dealing with
      difficult subjects such as death and whether this exposure was related to comfort
      level of the nurse during communication with patients and families regarding
      death. Findings of this study benefit nurse educators and nurses involved in
      staff development because the results indicate that comfort level of the nurse
      during communication with patients and families is adversely affected by an
      increase in the nurse's own death anxiety, and positively affected by exposure to
      communication education. Thus, these results indicate a need for education in
      this area. The next step is to identify the most effective type, objectives, and
      content of this type of education.

PMID- 15731641
TI  - Online degrees for nurses: a flexible alternative.
AB  - Online degree programs are a popular and flexible alternative for nurses. Online
      courses offer nurses the opportunity to complete an undergraduate or graduate
      degree from their homes while they work and raise their families. Online courses
      are different from traditional classroom courses, so nurses need know what to
      expect. Staff educators are a key resource to staff nurses regarding returning to
      school for degrees.

PMID- 15731642
TI  - Continuing education needs of currently practicing nurses toward the self-care
      management of patients with type 2 diabetes.
AB  - Today, self-management education is a critical part of the medical plan for
      people with diabetes. The purpose of this study was to examine the five domains
      of continuing education needs of currently practicing nurses toward the self-care
      management of patients with type 2 diabetes. The author identified significant
      differences between direct care practitioners and educators in four domains:
      assessment skills, knowledge area, attitudes and values, and barriers. It is
      important for educators to understand the learning needs of direct care
      practitioners in order to provide appropriate education.

PMID- 15731643
TI  - A gaming adventure.
AB  - Nurse orientees regularly express concern about managing difficult clinical
      situations. Using this information, preceptors developed an educational
      "adventure" game, incorporating clinical scenarios applicable to an inpatient
      psychiatric treatment program. The scenarios are timeless and can be generalized
      to other healthcare settings. This game has proven to be fun, effective, and
      nonthreatening and it integrates easily into staff training.

PMID- 15731658
TI  - Composite tissue allograft transplantation of cephalocervical skin flap and two
      ears.

PMID- 15731660
TI  - Sotos syndrome: surgical correction of abnormal craniofacial features.

PMID- 15731661
TI  - Allogeneic membranous bone grafting for a large calvarial defect.

PMID- 15731662
TI  - Body piercing: to what depths? An unusual case and review of associated problems.

PMID- 15731663
TI  - Mycobacterium marinum infections of the upper extremity.
AB  - A significant number of patients infected with Mycobacterium marinum have been
      treated at the Curtis National Hand Center in Baltimore, Maryland. The purpose of
      this study was to review the authors' experience with M. marinum infections of
      the upper extremity. Twenty-nine patients were identified and their charts were
      reviewed for all factors related to diagnosis and treatment. The most common
      presenting symptoms were swelling (n = 25) and pain (n = 14). Only 69 percent of
      patients could correlate their injury with aquatic activities. The mean time from
      injury to diagnosis was 5.2 months. Acid-fast bacilli stains were positive in
      only 22 percent of specimens. The mean number of procedures was 1.75, with the
      majority being tenosynovectomy. The mean duration of antibiotic therapy was 6
      months. Clinical history, pathological evaluation, and a high clinical suspicion
      can lead to early diagnosis and introduction of antibiotics. The authors'
      patients were successfully treated with 6 months of antibiotic therapy and early
      surgical intervention.

PMID- 15731664
TI  - Predictors of velopharyngeal insufficiency in cleft palate orthognathic surgery.
AB  - The purpose of this study was to appraise the value of preoperative speech
      assessments, nasopharyngoscopy, and surgical models as predictors of
      velopharyngeal deterioration after a Le Fort I maxillary advancement in cleft
      patients. This retrospective study involved a series of 26 cleft patients (16
      unilateral complete and nine bilateral complete cleft lips and palates, and one
      isolated complete cleft palate) who had Le Fort I maxillary advancements between
      March 1, 1993, and February 7, 1996. The 13 male patients and 13 female patients
      ranged in age from 15.3 to 46 years (mean age, 19.5 years). Four of these
      patients had previously undergone pharyngeal flap surgery. Eleven patients had
      palatal fistulas and one had a bifid uvula that was repaired at the time of
      orthognathic surgery. Patients with perceived hypernasal speech preoperatively
      all had hypernasality after advancement (nine of nine). Velopharyngeal
      insufficiency was observed in two of the 16 whose resonance preoperatively was
      within normal limits. Speech assessment, therefore, predicted accurately the
      postoperative status in 23 of 26 patients. Twelve patients had preoperative
      nasopharyngoscopy that indicated a high risk for velopharyngeal insufficiency
      (borderline or inadequate closure). Nine of these patients had postoperative
      velopharyngeal insufficiency. Two of the 14 patients not judged at risk by
      nasopharyngoscopy developed velopharyngeal insufficiency. Therefore, 21 of the 26
      patients were accurately predicted by nasopharyngoscopy. Scoping detected
      borderline velopharyngeal insufficiency in one patient who was not detected by
      speech alone. The combined predictive value of speech and scope identified all
      but one patient who would develop postoperative velopharyngeal insufficiency. The
      degree of anteroposterior movement determined from surgical models was not
      predictive of the outcome. Patients with hypernasal speech preoperatively
      continue to have hypernasal speech after Le Fort I advancement. Preoperative
      perceptual speech assessment by specially trained speech-language pathologists is
      an excellent test for predicting postoperative velopharyngeal insufficiency
      status. Nasopharyngoscopy is an invasive and resource-dependent test that should
      be assessed with respect to cost effectiveness. In this series, only one
      patient's risk was more accurately predicted using nasopharyngoscopy than by
      speech assessment alone.

PMID- 15731665
TI  - Maxillofacial growth in children with unilateral cleft lip and palate following
      secondary alveolar bone grafting: an interim evaluation.
AB  - This study evaluates the effect of alveolar bone grafting on the maxillofacial
      growth in children of mixed dentition with unilateral complete cleft lip-cleft
      palate. Twenty patients received an iliac crest alveolar bone graft between the
      ages of 6 years 10 months and 10 years 10 months, whereas 20 matched controls
      between the ages of 6 years 11 months and 10 years 6 months did not. Geometric
      morphometric assessments were used to localize alterations between the initial
      and final cephalographs in the two groups of cleft children, using Procrustes
      analysis and thin-plate spline analysis, in addition to conventional
      cephalometric techniques. It is concluded that no statistically significant
      difference in maxillofacial growth was found between the cleft children having
      received secondary alveolar bone grafting and the nongraft controls in general
      during the first to third postoperative years. Further investigation will be
      undertaken to determine the long-term effects after the age of skeletal maturity.

PMID- 15731666
TI  - Evaluation of a new measurement tool for facial paralysis reconstruction.
AB  - Evaluation of facial movement, including distance and direction, is essential for
      anyone interested in facial paralysis reconstruction. The authors' goal was to
      develop a measurement system that is simple, uses commercially available
      equipment, takes little time, and provides meaningful and accurate measurements.
      This technique is called the facial reanimation measurement system. It involves
      placing dots around the patient's mouth and video recording the patient
      performing maximal effort smiles. Using a video editing program, one frame
      showing the patient at rest is overlaid with a second frame showing the patient's
      smile. This overlaid image is imported into Adobe PhotoShop, where measurements
      are obtained using tools available in the program. Twenty patients were used to
      test interrater and intrarater reliability of the facial reanimation measurement
      system. The accuracy of the measurement process was tested by comparing 10 known
      distances and angles with those obtained using the facial reanimation measurement
      system. Both intrarater and interrater reliability of the distance and angle
      measurements are highly accurate, with intraclass correlations greater than 0.9.
      The facial reanimation measurement system is accurate to within 0.6 mm and 2.0
      degrees when compared with a "known" distance and angle. The facial reanimation
      measurement system has been used to measure smile movements of more than 200
      patients and has been demonstrated to be valuable for detecting changes of facial
      movements over time. This system is simple and economical and only requires 20
      minutes to perform. Although the authors demonstrated evaluation of smile
      movement, the system may be used to evaluate other movements, such as mouth
      puckering, eye closure, and forehead elevation.

PMID- 15731668
TI  - Skull base tumors: a comprehensive review of transfacial swing osteotomy
      approaches.
AB  - Numerous techniques have been proposed for the resection of skull base tumors,
      each one unique with regard to the region exposed and degree of technical
      complexity. This study describes the use of transfacial swing osteotomies in
      accessing lesions located at various levels of the cranial base. Eight patients
      who underwent transfacial swings for exposure and resection of cranial base
      lesions between 1996 and 2002 were studied. The mandible was the choice when wide
      exposure of nasopharyngeal and midline skull base tumors was necessary,
      especially when they involved the infratemporal fossa. The midfacial swing
      osteotomy was an option when access to the entire clivus was necessary. An
      orbital swing approach was used to access large orbital tumors lying inferior to
      the optic nerve and posterior to the globe, a region that is often difficult to
      visualize. Gross total tumor excision was possible in all patients. Six patients
      achieved disease control and two had recurrences. The complications of
      cerebrospinal fluid leak, infection, hematoma, or cranial nerve damage did not
      occur. After surgery, some patients experienced temporary symptoms caused by
      local swelling. The aesthetic result was considered good. Transfacial swing
      osteotomies provide a wide exposure to tumors that occur in the central skull
      base area. Excellent knowledge of the detailed anatomy of this region is
      paramount to the success of this surgery. The team concept is essential; it is
      built around the craniofacial surgeon and an experienced skull base neurosurgeon.

PMID- 15731667
TI  - Rhinoplasty and endoscopic surgery for functional and inflammatory nasal/sinus
      disorders.
AB  - The rhinoplastic surgeon when faced with nasal sinusitis has traditionally
      delayed aesthetic treatment of the nose, referring the patient to the ear, nose,
      and throat consultant until complete resolution of the inflammatory condition.
      Often, under such a scenario, the patient found the ear, nose, and throat
      procedure to be a traumatic experience that discouraged further surgery of an
      aesthetic nature. The advent of functional endoscopic sinus surgery has
      significantly modified the management of paranasal sinus disorders. This
      minimally invasive, sophisticated procedure can easily be combined with
      rhinoplasty. More recently, an endoscopic approach has been advocated for
      management of the septum and lower/middle turbinates. The authors call this
      functional endoscopic nasal surgery. Functional endoscopic nasal surgery allows a
      clearer view of the operative field (septum and turbinates), a more accurate
      correction of nasal obstruction, and better control of bleeding. Thus, endoscopic
      techniques permit the treatment of functional and inflammatory nasal disorders in
      a single stage, along with aesthetic improvement. Only the patient with severe
      sinusitis is unsuitable for combined therapy. The authors present their
      experience based on 72 consecutive cases of combined functional endoscopic sinus
      surgery/functional endoscopic nasal surgery with aesthetic rhinoplasty.
      Complications were minimal and functional failures were limited to 4 percent,
      whereas aesthetic outcomes remained uncompromised.

PMID- 15731669
TI  - Sentinel lymph node biopsy in the management of cutaneous head and neck melanoma.
AB  - Sentinel lymph node biopsy has revolutionized the surgical management of primary
      malignant melanoma. Most series on sentinel lymph node mapping have concentrated
      on extremity and truncal melanomas. The head and neck region has a rich and
      unpredictable lymphatic system. The use of sentinel lymph node mapping in the
      management of head and neck melanoma is evaluated. The authors conducted a
      retrospective review of patients treated for clinical stage I and stage II
      malignant melanoma of the head and neck with dynamic lymphoscintigraphy and gamma
      probe-guided sentinel lymph node biopsy. One hundred thirty-two patients (99 male
      patients and 33 female patients) were identified. The primary melanoma sites were
      the scalp (n = 54), ear (n = 14), face (n = 37), and neck (n = 27). Primary tumor
      staging was as follows: T1, 11; T2, 38; T3, 39; and T4, 44. Dynamic
      lymphoscintigraphy visualized sentinel lymph nodes in 128 patients (97 percent).
      In 71 cases (55 percent), a single draining nodal basin was identified, and in 57
      cases there were multiple draining nodal basins (two basins, 55; three basins,
      two). Sentinel lymph nodes were successfully identified in 176 of 186 nodal
      basins (95 percent). Positive sentinel lymph nodes were identified in 22 patients
      (17.6 percent). Sentinel lymph node positivity by tumor staging was as follows:
      T2, 10.8 percent; T3, 19.4 percent; and T4, 26.8 percent. Completion
      lymphadenectomy revealed residual disease in seven patients (33.3 percent).
      Sentinel lymph node mapping for head and neck melanoma can be performed with
      results comparable to those of other anatomical sites.

PMID- 15731670
TI  - Breast pathology and reduction mammaplasty.
AB  - Breast cancer is the tumor with the highest prevalence and incidence in women.
      Reduction mammaplasty is one of the most common procedures performed in Brazil by
      the plastic surgeon, and it is not uncommon for the surgeon to find a breast
      tumor during the operation or afterward, when the histopathological report is
      received. In this study, 2488 patient files were reviewed retrospectively. All
      patients had undergone reduction mammaplasty at the senior author's private
      clinic (the Ivo Pitanguy Clinic) between January of 1957 and December of 2002.
      Resected breast tissue was examined histopathologically. The objective of this
      study was to verify the occurrence of breast carcinoma found accidentally
      postoperatively. The senior author's team performed all of the operations and the
      same pathologist performed every histopathological examination. The
      histopathological test results were divided into two groups: benign lesions and
      tumors. The highest frequency of breast pathology was benign lesions, and of
      them, 80.8 percent involved fibrocystic changes and fibroadiposity. The tumor
      group was subdivided into benign tumors and malignant tumors. Among the benign
      tumors, fibroadenoma was the one most common, in 2.2 percent. The frequency of
      malignant tumors was 0.5 percent of all patients. Most of the histopathological
      lesions were found in patients between 30 and 50 years of age. A reduced number
      of patients had no lesions (3.7 percent). Lack of a pathological investigation or
      a cursory or hurried examination of any mammary tissue by the pathologist may
      overlook important lesions. In the analysis of these statistics, the concept of
      normal breast tissue was questioned.

PMID- 15731672
TI  - A comparison of complication rates in large and small inferior pedicle reduction
      mammaplasty.
AB  - The main objective of this retrospective study was to determine whether the rates
      of complications are higher in large reductions (> or =1000 g per breast) as
      compared with smaller reductions (< or =999 g per breast) using the inferior
      pedicle technique. A retrospective chart review of 133 consecutive patients
      operated on between October of 2000 and March of 2002 was undertaken.
      Complication data were recorded and analyzed on a per-breast basis. Two hundred
      sixteen breasts had reductions of 999 g or less, whereas 50 breasts had
      reductions of 1000 g or more. The overall mean follow-up period was 152 days
      (range, 20 to 522 days). There were no statistically significant differences in
      the rates of nipple necrosis, hematoma formation, seroma, delayed healing,
      culture-positive wound infection, fat necrosis, cyst formation, nipple sensation,
      or hypertrophic scarring between the large and small reductions. However, the
      rate of wound dehiscence was significantly lower in the smaller reduction group.
      The rates of wound dehiscence and hypertrophic scarring were also significantly
      lower in patients who had received at least 5 days of postoperative antibiotics.
      A statistically significant difference was also reported for clinical wound
      infection (p < 0.0005). Body mass index had no statistically significant effect
      on the rate of nipple necrosis, hematoma formation, fat necrosis, cyst formation,
      nipple sensation, or hypertrophic scarring. However, body mass index had a
      statistically significant effect on delayed healing, wound dehiscence, and
      culture-positive wound infection. A higher mean body mass index predicted a
      delayed healing, wound dehiscence, and infection. The inferior pedicle technique
      is a safe method of breast reduction regardless of degree of parenchymal
      resection. However, the use of postoperative antibiotics for at least 5 days is
      recommended to reduce rates of wound dehiscence and improve postoperative
      scarring.

PMID- 15731673
TI  - Alteration of nipple and areola sensitivity by reduction mammaplasty: a
      prospective comparison of five techniques.
AB  - The preservation of the sensitivity of the nipple-areola complex after reduction
      mammaplasty is an important goal. The authors performed this prospective study to
      accurately assess whether sensitivity changes are influenced by the weight of
      resection or the surgical technique. Eighty patients who underwent bilateral
      breast reduction (Lassus, 10 patients; Lejour, 13 patients; McKissock, 18
      patients; Wuringer, 20 patients; and Georgiade, 19 patients) were tested for
      sensitivity changes of the nipple and cardinal points of the areola with Semmes
      Weinstein monofilaments before surgery, at 3 weeks, and at 3, 6, and 12 months
      after surgery. Patient characteristics (age, body mass index, and preoperative
      sensitivity) were statistically similar in all groups. The mean resection weight
      was significantly smaller in the Lassus (540 g) and the Lejour groups (390 g)
      than in the Georgiade group (935 g). The sensitivity of the nipple and the
      inferior and lateral part of the areola was significantly lower after a superior
      pedicle technique (Lassus and Lejour) than after any other technique at 3 weeks
      and at 3, 6, and 12 months postoperatively. Insensate nipples and areolas were
      found only after breast reductions with the Lassus and the Lejour techniques
      (47.8 percent). Nipple sensitivity after breast reduction by the other techniques
      was unchanged (Wuringer, McKissock, and Georgiade) or sometimes even improved
      (Georgiade) as early as 3 weeks postoperatively. Changes in nipple and areola
      sensitivity after reduction mammaplasty depend on the surgical technique rather
      than the weight of resection. Superior glandular pedicle techniques that require
      tissue resections at the base of the breast are associated with a higher risk of
      injury to the nerve branches innervating the nipple-areola complex.

PMID- 15731675
TI  - Two options for perforator flaps in the flank donor site: latissimus dorsi and
      thoracodorsal perforator flaps.
AB  - Two types of perforators, septocutaneous and musculocutaneous, are found in the
      same donor site of the flank area, and two perforator flaps based on each
      perforator are clinically available. Therefore, it is necessary to distinguish
      them from one another using different nomenclatures. Accordingly, the perforator
      flap based on a musculocutaneous perforator is named according to the name of the
      muscle perforated, the latissimus dorsi perforator flap, and the perforator flap
      based on a septocutaneous perforator, located between the serratus anterior and
      latissimus dorsi muscles, is named according to the name of the proximal vessel,
      the thoracodorsal perforator flap. In this series of 42 latissimus dorsi
      perforator flaps, flap size ranged from 5 x 3 cm to 20 x 15 cm, and two
      complications were observed: a marginal necrosis in an extremely large flap (26 x
      12 cm) and a failure caused by infection. The thoracodorsal perforator flap was
      used in 14 cases, including two cases of chimeric composition. Flap size ranged
      from 4.5 x 3.5 to 18 x 15 cm, with no complications. In the two patterns of
      perforator flap that the author used, initial temporary flap congestion was
      observed in five latissimus dorsi perforator flap cases and two thoracodorsal
      perforator flap cases, when the flap was designed as a large flap or a less
      reliable perforator was selected. However, the congestion was not serious enough
      to cause flap necrosis. Several techniques, such as T anastomosis or inclusion of
      an additional perforator or a small portion of muscle, are recommended to prevent
      the initial flap congestion, especially when an unreliable perforator is
      inevitably used or when a flap larger than 20 cm long is required. A small
      portion of the muscle was included in six cases, when an unduly large or
      improperly long flap was planned. All of the flaps were successful and ranged
      from 22 x 7 to 15 x 28 cm, except for one case of distal flap necrosis in an
      extraordinarily large flap measuring 34 x 10 cm. Diverse selection of the
      perforator flap is one of the great advantages of the flank donor site, providing
      it with wider availability and more versatile composition for reconstruction or
      resurfacing.

PMID- 15731676
TI  - The midabdominal TRAM flap for breast reconstruction in morbidly obese patients.
AB  - The transverse rectus abdominis myocutaneous (TRAM) flap is ideal for
      postmastectomy reconstruction but is tenuous in morbidly obese patients. Because
      of their relatively high incidence of postoperative complications, morbidly obese
      patients are often not considered candidates for autogenous reconstruction. The
      midabdominal TRAM flap has a more favorable anatomy and may represent an
      alternative technique in this patient population. The records of 18 morbidly
      obese patients who underwent postmastectomy reconstruction using a mid-abdominal
      TRAM flap from 1998 through 2002 were retrospectively reviewed. The mid-abdominal
      TRAM flap territory includes more of the supraumbilical region than the
      traditional TRAM flap, corresponding to an area with more abundant
      musculocutaneous perforators and greater dependence on the superior epigastric
      vascular system. All patients underwent unipedicled mid-abdominal TRAM flap
      surgery. Four patients with previous subumbilical midline incisions had a delay
      procedure with ligation of the inferior epigastric vessels. Complications
      investigated were flap necrosis greater than 10 percent or sufficient to require
      surgical revision, abdominal donor-site breakdown, seroma formation, umbilical
      necrosis, abdominal wall bulging or hernia, deep vein thrombosis, infected mesh,
      surgical revisions, fat necrosis, and extended hospital stay. At a mean follow-up
      time of 15.6 months (range, 12 to 24 months), three patients had postoperative
      complications requiring surgical revision. Two of these patients had previous
      midline abdominal incisions. One patient had both partial flap necrosis and a
      donor-site complication. The second patient had partial flap necrosis, and the
      third had an abdominal donor-site complication. No occurrences of abdominal wall
      hernia, total flap loss, deep vein thrombosis, infected mesh, extensive surgical
      revision, or extended hospitalization were noted in this series. The mid
      abdominal TRAM flap represents an alternative method for postmastectomy breast
      reconstruction in morbidly obese patients. Autologous reconstruction using a
      midabdominal TRAM flap may be considered in this patient population; however,
      additional research is required to conclusively demonstrate an improved outcome
      when compared with traditional reconstructive methods.

PMID- 15731677
TI  - The safety of microvascular free tissue transfer in the elderly population.
AB  - The objective of this study was to evaluate the safety and thus the efficacy of
      microvascular free tissue transfer in the elderly patient population. Free flaps
      for different types of reconstructions were analyzed to verify whether free
      tissue transfer is feasible in the elderly. Between 1993 and 2003, 102 free flaps
      were performed in 94 patients who were aged 70 years or older. There were 75 male
      and 19 female patients, with a mean age of 73.8 years (range, 70 to 87 years).
      Different types of free flaps were performed for head and neck (n = 78), lower
      extremity (n = 12), and trunk and upper extremity (n = 4) reconstruction. Nine
      flaps underwent reexploration and four of them were lost, for an overall success
      rate of 96 percent. Medical complications in the postoperative period were
      further evaluated. A total of 32 medical complications were seen in 29 patients.
      Only one patient died because of postoperative complications. The frequency of
      medical complications was further analyzed in detail. Effects of American Society
      of Anesthesiologists status, operation time, and age on complication rate were
      evaluated statistically. Only American Society of Anesthesiologists status was
      statistically significant for the occurrence of postoperative medical
      complications; class III and IV patients were at higher risk than class I and II.
      Neither operation time nor age was predictive of postoperative complications.
      Microvascular free tissue transfer is a safe and reliable option in the elderly
      population. The success rate of free flaps is not different from that for other
      age groups. The rate of postoperative medical complications was 31 percent (29 of
      94 patients); most complications were in American Society of Anesthesiologists
      class III and IV patients.

PMID- 15731678
TI  - Management of complex groin wounds: preferred use of the rectus femoris muscle
      flap.
AB  - This study reviews our experience with the rectus femoris muscle flap for complex
      groin wound reconstruction. Over the past 5 years, the rectus femoris has become
      our routine method of groin wound reconstruction. The rectus femoris is harvested
      through a midanterior incision extending over the distal two-thirds of the thigh.
      The muscle is elevated on its pedicle and transposed into the groin wound defect
      either directly or through an intervening skin bridge. Hospital and outpatient
      records were reviewed for all patients undergoing groin wound reconstruction with
      this technique from 1999 through 2003. Thirty-seven rectus femoris muscle flaps
      were performed in 33 patients. The mean patient age was 65.3 years (range, 25 to
      88 years). Thirty groin wounds (81.1 percent) occurred after infrainguinal
      revascularization, 23 (76.7 percent) of which contained prosthetic material. Five
      (21.7 percent) of these wounds had their prosthetic material removed at the time
      of reconstruction. The remaining seven groin wounds (18.9 percent) occurred after
      femoral vessel cannulation for either cardiac or transplant surgery. There were
      no intraoperative mortalities and no anastomotic hemorrhages. There were no flap
      losses. Thirty-five of the 37 treated wounds healed (94.6 percent), 26 primarily
      (70.3 percent) and nine (24.3 percent) after delayed healing and contracture.
      Reoperation was performed in one patient for flap readvancement and in three
      patients for prosthetic graft removal after initial flap reconstruction. Two
      patients (6.1 percent) died during their hospitalization with persistent open
      groin wounds after flap reconstruction. All muscle flap donor incisions healed,
      with only two (5.4 percent) experiencing minimal delayed healing. There were no
      donor-site wound infections and no donor sites required reoperation. Thirty-three
      groin wounds (89.2 percent) demonstrated culture-positive microbial infection, 15
      (45.5 percent) of which were polymicrobial. The 30-day mortality rate was 15.2
      percent and the 6-month mortality rate increased to 27.2 percent, with
      multisystem organ failure as the most common cause. The rectus femoris muscle
      flap is an effective and reliable means of complex groin wound reconstruction.
      The muscle flap is dependable and the donor site is not problematic, even in the
      presence of peripheral vascular disease. On the basis of our clinical results, we
      believe that the rectus femoris muscle flap is the flap of choice for groin wound
      reconstruction.

PMID- 15731680
TI  - Donor-site morbidity of the pedicled rectus femoris muscle flap.
AB  - The rectus femoris muscle flap is well known for its reliable anatomy, the ease
      with which it can be harvested, and its great versatility. As a pedicled or free
      flap, it is used to cover soft-tissue defects and to recreate motor function.
      Although the muscle is very reliable, it is not well respected because of its
      assumed donor-site morbidity, such as weakened knee extension force and decreased
      range of motion of the knee. To date, these clinical assumptions have only rarely
      been quantified in terms of objective scores, concerning force deficit and
      functional or aesthetic outcome. From 1995 to 2002, the authors treated 24
      patients with pedicled rectus femoris muscle flaps. Fourteen patients were
      followed up. Follow-up time ranged from 3 to 56 months postoperatively. The
      results were evaluated by a standard questionnaire in which pain in relation to
      walking distance, subjective feeling of weakness, sensibility disorders, everyday
      function, and aesthetic aspects were assessed. Range of motion in the hip and the
      knee was measured. For objective verification of a decrease of maximal voluntary
      contraction force of the remaining quadriceps muscle and for detecting
      differences in true muscular capacity and voluntary activation, 10 patients with
      unilateral rectus femoris flaps were tested using the twitch interpolation
      technique. The authors' patients assessed the remaining function and the
      aesthetic result of the thigh as at least satisfactory. Two patients complained
      about pain and weakness in the thigh. Eight patients reported hypesthesia in the
      lateral suprapatellar region. The maximal voluntary contraction and true muscular
      capacity values were reduced by 21.8 percent and 18 percent, respectively, when
      compared with the healthy leg. The range of motion in the knee and hip was not
      influenced by muscle harvesting. The twitch interpolation technique revealed a
      mild voluntary activation deficit, probably caused by inhibitory regulation in
      the spinal cord. In conclusion, donor-site morbidity of the rectus femoris muscle
      flap is evident but well compensated. There is no decrease in active range of
      motion in the knee and hip. Patient satisfaction with the functional and
      aesthetic outcome was high.

PMID- 15731681
TI  - The medial adiposofascial flap of the leg: anatomical basis and clinical
      applications.
AB  - Despite recent advances in microsurgical techniques, coverage of lower leg
      defects by locoregional flaps remains indicated in selected cases. The interest
      in these types of flaps has improved because recent clinical work advocates that
      fascial and fasciocutaneous flaps can be well indicated for bone coverage. The
      anatomical study of the medial adiposofascial flap is presented in this article.
      The flap is based on the rich vascular network supplied by the saphenous artery
      and the posterior tibial artery perforators. This flap can be harvested on the
      anteromedial aspect of the leg and can be mobilized to cover defects located
      between the patella and the heel. This multiple blood supply makes it possible to
      harvest this flap in various ways, so various defects can be covered. To confirm
      and prove the versatility and clinical value of this flap, the authors have
      studied a series of 22 cases in which this flap was used for coverage of lower
      leg defects. For these defects, especially when situated in the lower third or
      around the heel and ankle, coverage by a free flap is most often the only
      proposed solution. However, the authors have obtained excellent results in the
      majority of these cases, avoiding a free flap procedure. Moreover, in this way,
      the option of using a free flap remains possible if needed. There is minimal
      donor-site morbidity and a high functional and aesthetic outcome, making this
      flap a first-choice flap in selected cases of lower leg defects.

PMID- 15731683
TI  - Cadaveric study of sonographically assisted percutaneous release of the A1
      pulley.
AB  - The purpose of this study was to assess the value of using intraoperative
      sonography to assist percutaneous release of the A1 pulley in cadavers. By
      detailed sonographic examination and anatomical exploration, the authors
      determined the correlation of the actual A1 and A2 pulleys (and adjacent
      neurovascular bundles not visualized by sonography) to the clearly visualized
      flexor tendons and the metacarpophalangeal joint. The authors also evaluated
      their effectiveness as landmarks and the effectiveness of real-time sonographic
      monitoring during percutaneous release. Experiments were performed on 80 fingers
      and 20 thumbs in 10 cadavers. All digits were sonographically examined. The
      clearly delineated bony landmarks of the metacarpophalangeal joint were measured
      and marked. The A1 and A2 pulleys and the neurovascular bundles were surgically
      exposed, and their relation to the markers made during sonographic examination
      was measured. Using these parameters, sonographically assisted percutaneous
      release of the A1 pulley with a custom-made hook knife was performed on the
      contralateral side. The completeness of the A1 release and the potential risk of
      injuries to the A2, flexor tendon, and neurovascular bundles in each digit were
      examined. Results showed good correlation between the actual length of the A1
      pulleys and the sonographically determined distance between the bony prominences
      of the metacarpophalangeal joint in all digits. Release was complete in 48 of the
      50 digits (96 percent) and partial in two, with no injuries to neurovascular
      bundles. Sonography can clearly delineate the flexor tendon and underlying bony
      boundary of the metacarpophalangeal joint, which is useful in directing the
      percutaneous release of the A1 pulley. Sonography can also provide real-time
      intraoperative monitoring. The results using this new release technique were
      adequate. The method is safe and its clinical application should be encouraged.

PMID- 15731682
TI  - Dupuytren's fasciectomies in 60 consecutive digits using lidocaine with
      epinephrine and no tourniquet.
AB  - Dupuytren's contracture is a common hand problem. Its treatment, other than
      percutaneous fasciectomy, is an outpatient operation performed with the patient
      under regional or general anesthesia. If local anesthetics are used, they are
      used without epinephrine, and an arm or forearm tourniquet is essential. Multiple
      reviews have described the safety of local anesthetics with epinephrine in the
      digits. This study is a retrospective review of operations performed by the same
      surgeon in the hospital (43 digits) versus the office using local anesthetics
      with epinephrine and no tourniquet (60 digits). Results and complications were
      compared and tabulated. The hospital and epinephrine groups were comparable
      regarding preoperative measurements. Postoperative improvement in extension at
      the metacarpophalangeal and proximal interphalangeal joints was similar in both
      the hospital and epinephrine groups. Complications, including digital nerve and
      artery injuries, infections, and hematomas, were similar between the groups.
      There were no cases of digital necrosis or gangrene in the epinephrine group,
      even though one patient sustained a transection of a digital artery at the
      proximal interphalangeal joint. Because of the similarities in results and
      complications, there does not seem to be an advantage to performing Dupuytren's
      excisions with full arm tourniquet and outpatient admission in many cases. Local
      anesthetics with epinephrine are safe in the treatment of Dupuytren's
      contracture, although both the use of digital epinephrine and the use of
      mechanical tourniquets carry the potential for complications. Visibility is
      similar to that for facial or head and neck surgery and is aided by the use of
      loupe magnification. The old dogma against its use in the fingers is refuted, as
      seen by the results in these 60 consecutive Dupuytren's fasciectomies and the
      results of other authors.

PMID- 15731684
TI  - Assessment of the immune response to dose of nerve allografts.
AB  - Nerve allotransplantation provides a limitless source of nerve graft material for
      the reconstruction of large neural defects. It does require systemic
      immunosuppression or induction of immune unresponsiveness to prevent allograft
      rejection. It is unknown whether a greater volume of nerve graft material will
      increase the risk of rejection or the need for more intensive immunosuppression.
      This study assessed the relationship between the quantity of nerve tissue
      transplanted and the magnitude of the resulting immune response. Forty female
      (BALB/c) mice were randomly assigned to two groups that received either nerve
      isografts (BALB/c) or nerve allografts (C57BL/6). Each group was then subdivided
      into two groups that received either one or 10 sciatic nerve graft inlays.
      Histological and immunological assessments were performed at 10 days after
      engraftment. Histologic analysis demonstrated greater cellular infiltration in
      the allograft than the isograft groups but no appreciable difference in
      infiltration related to quantity of transplanted nerve tissue. In vitro
      assessments of the immune response using mixed lymphocyte assays and limiting
      dilution analysis similarly demonstrated a robust immune response to allografts
      but no effect on quantity of transplanted nerve tissue. These data suggest that
      larger peripheral nerve allografts may not be subject to increased risk for
      rejection.

PMID- 15731685
TI  - The effect of rate of distraction osteogenesis on structure and function of
      anterior digastric muscle fibers.
AB  - The authors hypothesized that distraction at a rate of 3 mm/day, compared with
      mandibular distraction at a rate of 1 mm/day, would produce a maladaptive
      response in adjacent muscles of mastication. The authors further hypothesized
      that the maladaptive response would manifest at the single fiber level by means
      of increased sarcomeric heterogeneity, decreased maximum force output, and
      increased susceptibility to stretch-induced injury. In an ovine model,
      distraction osteogenesis of the right hemimandible was performed at either 1
      mm/day for 21 days (n = 2) or 3 mm/day for 7 days (n = 2) to achieve a total
      distraction distance of 21 mm. The left hemimandibles served as controls. After a
      consolidation period of 2 days, the anterior digastric muscles were harvested; in
      six randomly selected single fibers from each muscle, maximum calcium-activated
      force (Po) was measured at optimal sarcomere length. The amount of damage to the
      sarcomeres in each fiber was assessed microscopically. To test susceptibility to
      contraction-induced injury, each fiber was given an activated stretch of 20
      percent. Compared with control fibers and fibers distracted at 1 mm/day, maximum
      tetanic force (Po) was significantly lower in fibers distracted at 3 mm/day.
      Compared with control fibers, specific Po (Po/cross-sectional area) was lower in
      fibers distracted at 3 mm/day. The number of sarcomeres appearing damaged in
      fibers distracted at 3 mm/day was significantly higher than in control fibers or
      in fibers distracted at 1 mm/day. A greater deficit in Po was observed after a
      single activated stretch in fibers distracted at 3 mm/day than in control fibers
      or in fibers distracted at 1 mm/day. The authors conclude that distraction of the
      anterior digastric muscle in sheep at 3 mm/day produces a maladaptive response in
      the muscle fibers but a rate of 1 mm/day is tolerated by the muscle fibers. These
      data are consistent with the hypothesis that distraction of skeletal muscle at
      high rates results in increased heterogeneity of sarcomere lengths and that this
      increase in heterogeneity is the most likely potential mechanism resulting in
      whole muscle force deficits and in increased susceptibility to stretch-induced
      injury in distracted muscles.

PMID- 15731686
TI  - FGF-2 acts through an ERK1/2 intracellular pathway to affect osteoblast
      differentiation.
AB  - An abundance of genetic and experimental data have suggested that fibroblast
      growth factor (FGF) signaling plays a central role in physiological and
      pathological cranial suture fusion. Although alterations in the differentiation
      and proliferation of sutural osteoblasts may be a key mediator of this process,
      the mechanisms by which FGF signaling regulates osteoblast differentiation remain
      incompletely understood. In the current study, the authors show that recombinant
      human FGF-2 alters osteoblastic expression of bone morphogenetic protein-2 and
      Msx-2 in vitro to favor cellular differentiation and osteoinduction. The ERK1/2
      intracellular signaling cascade was shown to be necessary for recombinant human
      FGF-2-mediated bone morphogenetic protein-2 transcriptional changes. Furthermore,
      the cellular production of an intermediate transcriptional modifier was found to
      be necessary for the recombinant human FGF-2-mediated gene expression changes in
      bone morphogenetic protein-2 and Msx-2. Together, these findings offer new
      insight into the mechanisms by which FGF-2 modulates osteoblast biology.

PMID- 15731687
TI  - The effect of interleukin-8 on the viability of injected adipose tissue in nude
      mice.
AB  - Adipose tissue injection as a free graft for the correction of soft-tissue
      defects is a widespread procedure in plastic surgery. The main problem in
      achieving long-term soft-tissue augmentation is partial absorption of the
      injected fat and hence the need for overcorrection and re-injection. The purpose
      of this study was to improve the viability of the injected fat by the use of
      interleukin-8. The rationale for the use of interleukin-8 was its abilities to
      accelerate angiogenesis and attract inflammatory cells and fibroblasts, providing
      the injected adipocytes more feeding vessels and a well-established graft bed to
      enhance their viability. Human adipose tissue, obtained by suction-assisted
      lipectomy, was re-injected into the subcutis in the scalp of nude mice.
      Interleukin-8 (0.25 ng) was injected subcutaneously to the scalp as a preparation
      of the recipient site 24 hours before the fat injection and was added to the fat
      graft itself (25 ng per 1 cc of injected fat). In the control group, pure fat
      without interleukin-8 was injected and no interleukin-8 was added for the
      preparation of the recipient site. One cubic centimeter of fat was injected in
      each animal in both the study and control groups. There were 10 animals in each
      group. The animals were euthanized 15 weeks after the procedure. Graft weight and
      volume were measured and histologic evaluation was performed. In addition,
      triglyceride content and adipose cell sizes were measured as parameters for fat
      cells viability. Histologic analysis demonstrated significantly less cyst
      formation in the group treated with interleukin-8. No significant differences
      were found between the groups with regard to graft weight and volume or the other
      histologic parameters investigated. No significant differences were demonstrated
      in adipose cell sizes and their triglyceride content. In conclusion, less cyst
      formation, indicating improved quality of the injected fat, can be obtained by
      the addition of interleukin-8. Further studies of various dosages of interleukin
      8 and their long-term effect are required before these encouraging results could
      be applied clinically.

PMID- 15731688
TI  - Inhibiting scar formation in rat wounds by adenovirus-mediated overexpression of
      truncated TGF-beta receptor II.
AB  - The purpose of this study was to explore the possibility of inhibiting wound
      scarring by blocking TGFbeta signaling of wound cells by means of a gene therapy
      approach. Normal dermal fibroblasts were infected in vitro either with
      recombinant adenovirus encoding a truncated TGFbeta receptor II (Ad-tTGF-betaRII)
      or with [beta]-galactosidase adenovirus (Ad-beta-gal). TGF-beta1 gene expression
      in infected fibroblasts was analyzed by Northern blot. In vivo, 1x10(9) plaque
      forming units of Ad-tTGF-betaRII were intradermally injected into the dorsal skin
      of 10-day-old newborn Sprague-Dawley rats (n = 10). For gene therapy, 1x10(9)
      plaque-forming units of Ad-tTGF-betaRII viruses were injected intradermally at
      the right side dorsal skin of another set of same aged Sprague-Dawley rats as the
      experimental group (n = 15). In the control group, 1x10(9) plaque-forming units
      of Ad-beta-gal (n = 11) or the same volume of saline (n = 4) was injected at the
      left side skin of the same rats. A 5-mm-long full-thickness incisional wound was
      created at the injection sites of each rat 2 days after injection. Wound tissues
      were harvested at day 3 (n = 2), day 7 (n = 2), and day 14 (n = 11) after
      wounding for histological analysis. Scar area of wound tissues harvested at day
      14 was quantitatively analyzed. The results showed that TGF-beta1 gene expression
      was markedly down-regulated in Ad-tTGF-betaRII infected fibroblasts compared with
      Ad-beta-gal infected cells. In vivo, adenovirus-mediated transgene expression in
      rat skin reached a peak level at day 2 after injection and the expression
      gradually decreased afterward. Inhibited inflammatory reaction was also observed
      in the treated wounds with significantly reduced inflammatory cells (p < 0.05).
      Moreover, in all 11 rats, the experimental wound at day 14 had much less scarring
      than its control wound of the same rat, with an average of 49 percent reduction
      of the scar area (p < 0.05). Furthermore, more panniculus muscles were repaired
      in the experimental wounds (nine of 11) than in the control wounds (two of 11) (p
      < 0.05). These results indicate that gene therapy by targeting wound TGF-beta can
      effectively inhibit wound scarring and may potentially be applied to clinical
      scar treatment.

PMID- 15731689
TI  - An innovative management of detached palatal mucoperiosteal flap from the hard
      palate (hanging palate).

PMID- 15731690
TI  - Total lower lid support with auricular cartilage graft.

PMID- 15731691
TI  - A different method of fingertip reconstruction with the thenar flap.

PMID- 15731693
TI  - Prophylactic mastectomy: indications, options, and reconstructive alternatives.
AB  - Prophylactic mastectomy continues to be a controversial procedure as a preventive
      tool against breast cancer. Recent research and other scientific advances,
      however, have refocused attention on better risk estimation, evidence of
      efficacy, and improvements in reconstruction. The recently discovered genetic
      markers BRCA1 and BRCA2 have become increasingly important in determining risk; a
      BRCA1-positive patient's risk of developing breast cancer by the age of 65 is
      estimated at 50 percent to 80 percent. BRCA1- and BRCA2-positive breast cancers
      also tend to be higher grade and occur in younger women (making mammography less
      effective). Genetically linked breast cancers are usually estrogen receptor
      negative, making them less susceptible to chemoprevention. Various predictive
      models and recommendations by experts in the field are also available for today's
      clinicians to ascertain who should be genetically tested. The benefit of
      bilateral prophylactic mastectomy, although difficult to estimate, can be
      evaluated by looking at the incidence of breast cancer in studies of patients who
      have previously undergone prophylactic mastectomy. The estimated risk reduction
      from these studies is 80 percent to 95 percent. Similarly, life expectancy is
      believed to be increased from 2.9 to 5.3 years. The psychological benefits
      include a 70 percent rate of satisfaction and a decrease in emotional concern
      over developing breast cancer by 74 percent of women who underwent prophylactic
      mastectomy. Although reconstruction results may vary, most patients have been
      very satisfied and some may achieve cosmetic results that are better than their
      preoperative situation. Patient selection for specific types of reconstruction
      after prophylactic mastectomy and the decision to proceed should be based on
      surgical risk and the likelihood of a good outcome. The choice of mastectomy
      incision should consider the size of the breast, preexisting scars, patient risk
      factors, and the planned method and goal of reconstruction. The authors propose
      certain guidelines based on degree of ptosis and cup size when planning
      prophylactic mastectomies with reconstruction. In certain cases, a nipple-sparing
      mastectomy may provide cosmetic advantages that could outweigh the additional
      oncologic risk.

PMID- 15731694
TI  - Early postoperative efficacy of fibrin glue in face lifts: a prospective
      randomized trial.
AB  - Fibrin glue is increasingly finding use in plastic surgery at the clinical and
      basic science level. The authors conducted a prospective, nonblinded, randomized,
      controlled trial in 30 patients undergoing face lifts to examine the efficacy of
      fibrin glue in reducing postoperative wound drainage, hematomas, and, in
      particular, the degree of ecchymosis and edema at 24 hours and at 8 days.
      Patients were their own controls and were randomized to have the glue on one side
      of their face only to compare the glued and unglued sides. The patients ranged in
      age from 42 to 72 years (mean age, 60 years). There was one major hematoma
      requiring surgical evacuation. In the remaining 29 patients, the mean drainage on
      the glued side was 26 ml, compared with 33.5 ml on the control, unglued side.
      This difference was statistically significant numerically (p = 0.037) but was not
      thought to be surgically significant. Comparing scores among grades of hematomas,
      ecchymosis, and edema, there were minimal differences between the glued and
      unglued sides. This study suggests that fibrin glue may not be as beneficial as
      previously thought in reducing ecchymosis and edema in the early postoperative
      period after face lifts, and its future role is discussed.

PMID- 15731696
TI  - The use of botulinum toxin type A in aesthetic mandibular contouring.
AB  - The lower third of Asian faces is wider than that of Caucasians and it is
      determined by the size and width of the mandibular bone and the thickness of
      muscles and subcutaneous fat tissues surrounding it. Efforts to create an
      aesthetically slim and smooth facial contour line in nonobese people have led the
      authors to focus on two approaches: surgical resection of the masseteric muscle
      and modeling ostectomy of the square-angled mandibular bone. Because these
      procedures present some problems, the authors adopted a nonsurgical concept that
      chemically denervates muscles and reduces the bulk of the muscle. The authors
      have conducted a total of 1021 clinical cases from March of 2001 through
      September of 2002, in which patients were treated with botulinum toxin type A
      (Dysport; Ipsen Ltd, Slough, United Kingdom) for remodeling the lower facial
      contour line; 383 of those cases were followed up for at least 3 months after the
      initial injection. A database was made by measuring the change in the thickness
      of the injected muscle with an ultrasonogram. Eleven patients underwent resection
      of the mandibular angle before injection. The preinjection ostectomy group was
      involved in the study as a result of their dissatisfaction with the surgical
      results; they had a rather thick masseter muscle and not a bone problem. Some had
      both bone problems and a thick masseter muscle. Three months after the botulinum
      toxin injection, the thickness of the muscle was reduced by 31 percent on
      average. The atrophic effect of injection was observed after 2 to 4 weeks for
      most patients. Seventy percent of the 383 patients tracked were greatly satisfied
      with the result, with another 23 percent generally satisfied. No long-term side
      effects were reported. Masseteric hypertrophy is frequent in Asians because of
      racial characteristics and dietary habits. Botulinum toxin type A has made a new
      epoch in facial contouring for Asians. Considering that Asians have a prominent
      malar and a prominent mandible angle, the reduction in the thickness of the
      masseter can provoke relative prominence of the malar and mandible angle.
      Therefore, precise indication and anatomy of the facial muscle should be
      thoroughly understood, which will decrease the incidence of side effects and
      problems. Botulinum toxin type A (Dysport) injection is simple in technique, has
      few side effects, and promises a rapid return to daily life. The authors conclude
      that the injection of botulinum toxin type A can replace surgical masseter
      resection.

PMID- 15731697
TI  - Female college students and cosmetic surgery: an investigation of experiences,
      attitudes, and body image.
AB  - This large, multisite study investigated female college students' experiences
      with and attitudes about cosmetic surgery. The study also assessed the
      relationship between several aspects of body image, including appearance
      satisfaction and investment and symptoms of body dysmorphic disorder, and
      interest in cosmetic surgery. Thirty (5 percent) of the 559 women surveyed
      reported that they had undergone cosmetic surgery. Two thirds of respondents
      reported knowing someone who had received cosmetic surgery, and approximately one
      third indicated that a family member had undergone surgery. Overall, participants
      held relatively favorable attitudes about surgery. Regression analysis suggested
      that a greater psychological investment in physical appearance and greater
      internalization of mass media images of beauty predicted more favorable attitudes
      toward cosmetic surgery. Fourteen women (2.5 percent) screened positive for body
      dysmorphic disorder based on the nature and severity of their self-reported body
      image concerns. Results of this study provide new information on young women's
      experiences and attitudes about cosmetic surgery and how these attitudes relate
      to body image.

PMID- 15731698
TI  - Minimal surgical access to treat gynecomastia with the use of a power-assisted
      arthroscopic-endoscopic cartilage shaver.
AB  - Gynecomastia is the most common benign condition of the male breast. The authors
      present a new method of treatment for gynecomastia that combines traditional
      liposuction in conjunction with a shaver technique to effectively remove the
      fibrofatty and the glandular tissues of the male breast and avoid areolar
      incisions. Twenty-five patients were treated in this fashion, and each patient
      demonstrated a smooth, masculine breast contour with well-concealed scars in the
      inframammary folds, eliminating the stigma of breast surgery. The procedure is
      technically straightforward and provides consistent results. It is offered as an
      additional option for the treatment of gynecomastia.

PMID- 15731699
TI  - Teenage breast augmentation: validating outcome data and statistics in plastic
      surgery.

PMID- 15731700
TI  - Mohs surgery: an informed view.

PMID- 15731701
TI  - A novel method of debridement of fat necrosis in reconstructed breasts.

PMID- 15731702
TI  - Is it possible to predict the duration of seroma?

PMID- 15731703
TI  - Discard little, learn more: the real tissue training model.

PMID- 15731704
TI  - Prefabricated dorsalis pedis flap for resurfacing exposed bone in the distal
      third of the leg.

PMID- 15731705
TI  - A total lower lip reconstruction with a composite radial forearm-palmaris longus
      tendon flap: a clinical series.

PMID- 15731707
TI  - A new fluid cup for electrocoagulation.

PMID- 15731706
TI  - Further advantages of using the subfascial implant in terms of capsular
      formation.

PMID- 15731708
TI  - Bone Wax as a template for harvesting composite grafts.

PMID- 15731709
TI  - Arterial supply to type II muscle after fasciocutaneous free flap transfer.

PMID- 15731710
TI  - A new template model prepared from synthetic plaster cast for experimental burn
      research.

PMID- 15731713
TI  - Potential for epinephrine overdose in liposuction.

PMID- 15731711
TI  - Primary hypotension: a contraindication to free tissue transfer?

PMID- 15731714
TI  - Soft-tissue simulator: helping trainees with fracture fixation.

PMID- 15731715
TI  - Sensory innervated superior gluteal artery perforator flap for reconstruction of
      sacral wound defect.

PMID- 15731716
TI  - Hyoid bone syndrome.

PMID- 15731717
TI  - Anterior thoracic hypoplasia: a separate entity from Poland syndrome.

PMID- 15731719
TI  - Vascular lesions of the lip: an aid to resection.

PMID- 15731720
TI  - The prone position in otoplasty.

PMID- 15731721
TI  - An ocular orthosis for frontonasal flaps.

PMID- 15731722
TI  - Outbreak of atypical mycobacteria infections in U.S. Patients traveling abroad
      for cosmetic surgery.

PMID- 15731724
TI  - Scar management after breast surgery: preliminary results of a prospective,
      randomized, and double-blind clinical study with aldara cream 5% (imiquimod).

PMID- 15731723
TI  - A simple technique for bloodless surgery.

PMID- 15731725
TI  - Soft-tissue implantable materials A to Z.

PMID- 15731726
TI  - Marvels of plastic surgery.

PMID- 15731727
TI  - Metastasis of breast cancer in the donor site after breast reconstruction with a
      latissimus dorsi flap.

PMID- 15731728
TI  - Seven more tips for the operating room.

PMID- 15731730
TI  - The vacuum expandable condom mold for reconstruction of the vagina.

PMID- 15731731
TI  - Local necrotizing skin infections in an HIV patient with porphyria cutanea tarda.

PMID- 15731732
TI  - Vertical scar reduction mammaplasty refinements.

PMID- 15731733
TI  - Excess skin following weight loss: cutis pleonasmus.

PMID- 15731735
TI  - [Thyroid hormone levels and thyroid dysfunction of French adults participating in
      the SU.VI.MAX study].
AB  - Abnormal thyroid function has important public health consequences. However, the
      various degrees of thyroid dysfunction remain unsettled. The SU.VI.MAX cohort
      provided a unique opportunity to conduct a cross-sectional study of abnormal
      thyroid function in a large representative population of 11256 men and women
      representing the geographic distribution of the French continental adult
      population. Thyroid status was measured, in fasting blood samples, at baseline in
      1994-1995. Serum thyrotropin (TSH) levels (abnormal < 0.4 mU/l or > or =4.0 mU/l)
      and free thyroxine (fT4) were both performed in duplicate on the same sample.
      Subjects with previous or present thyroid diseases or who were taking thyroid
      hormones or antithyroid drugs (n=920) were excluded (8.1%). Thus, the final study
      group consisted of 10346 subjects, 4121 men aged 45-60 years (mean +/-SD) (51.8+/
      4.7 yrs), 2641 women aged 35-44 years (40.6+/-2.8 yrs), and 3584 women aged 45-60
      years (51.4+/-4.4 yrs). Median (2.5th and 97.5th percentiles) for TSH (mU/l) were
      1.52 (0.20-4.54) for men, 1.78 (0.22-5.54) for women aged 35-44 years, and 1.96
      (0.22-6.80) for women aged 45-60 years. The TSH distribution of women was shifted
      to the right compared with men. Arithmetic mean fT4 (+/-SD) was 10.7+/-1.7 ng/l
      (13.8 +/-2.2 pmol/l) for men and 10.9+/-1.8 ng/l (14.0+/-2.3 pmol/l) for women.
      The prevalence of abnormal TSH values in men, and in women (35-44 yrs and 45-60
      yrs) were TSH<0.4 mU/l 7.0%, 5.3% and 4.4%; TSH 4.0-9.9 mU/l 4.0%, 7.2% and 11.1%
      and TSH > or =10.0 mU/l 0.2%, 0.4% and 0.7%, respectively. Geometric mean serum
      TSH and arithmetic mean serum fT4 concentrations showed significant overall inter
      regional differences for men and women (p<0.0001). There was also an inter
      regional difference in the prevalence of thyroid dysfunction for men (p=0.003),
      and for the older group of women (i.e. > or =45 yrs) (p=0.04) exclusively. Over
      the age of 45 years, the women: men ratio for unrecognized elevated TSH levels (>
      or =4.0 mU/l) was 2.82, whereas it was 0.64 for low TSH levels (<0.4 mU/l). In
      summary, abnormal TSH values and thyroid dysfunction were more prevalent in women
      than men, increased with age and were significantly associated with environmental
      factors. A high prevalence of identified thyroid diseases in the French
      population was confirmed by the high number of subjects in this study with
      laboratory evidence of abnormal biochemical thyroid function. Further studies are
      needed to determine the geographical determinants of thyroid dysfunctions,
      especially regional differences in iodine intakes, and to assess the long-term
      adverse effects of biochemical thyroid dysfunction on all-cause morbidity.

PMID- 15731737
TI  - The challenge of once a day HIV treatment.

PMID- 15731738
TI  - Therapeutic drug monitoring of antiretroviral agents scenario.
AB  - The efficacy of antiretroviral treatment (ART) may be limited by pharmacological
      factors. Dose-response relationship exists for many antiretroviral agents, and
      failure to maintain adequate concentrations may allow the development of viral
      resistance, thereby decreasing the probability of response of current and
      subsequent therapies. Fixed dosage of antiretroviral agents may result in
      different systemic and intracellular concentrations of drugs (interindividual
      variability). Therapeutic drug monitoring (TDM) consists of individualising
      dosages with the aim of maximising the efficacy of treatment while minimising its
      toxicity. The combination of pharmacokinetic-pharmacodynamic relationships for
      antiretroviral therapy and the presence of a wide interpatient variability in
      drug exposure support the application of TDM in HIV-infected individuals.
      Prospective clinical trials assessing the clinical usefulness of this strategy
      have shown contradictory results, pointing out the need to consider different
      issues when performing TDM of ART. Pharmacological and resistance data should be
      combined in one parameter (inhibitory quotient) in antiretroviral-experienced
      patients. Protease inhibitors exhibit a moderate to high degree of binding to
      plasma proteins, and in vitro inhibitory concentrations need to be corrected by
      this factor. The best method to individualize the dosage regimen has not been
      identified yet. Finally, participation of different laboratories in external
      cross-validation programmes is crucial to ensure that results are accurate.

PMID- 15731739
TI  - Nucleoside/nucleotide reverse transcriptase inhibitor drug interactions.
AB  - Since their advent the nucleoside and nucleotide reverse transcriptase inhibitors
      have consolidated their position as the 'backbone' of many antiretroviral therapy
      regimens. The ability of this class of drugs to combine successfully with members
      of their own as well as other antiretroviral classes has enabled the effective
      suppression of HIV replication to occur. Many of these therapeutic combinations
      rely on synergistic interactions to achieve this. There are, however, also many
      unfavourable pharmacokinetic and pharmacodynamic interactions between the members
      of nucleoside/nucleotide reverse transcriptase inhibitors, as well as with other
      antiretroviral classes and non-HIV drugs. This article aims to identify
      clinically relevant, beneficial and detrimental interactions of this class of
      antiretroviral agent.

PMID- 15731740
TI  - Pharmacokinetics of Telzir (fosamprenavir).
AB  - Fosamprenavir is a recently licensed protease inhibitor (PI) for the treatment of
      patients with HIV. It has potent antiviral activity when boosted by ritonavir and
      produces durable virological suppression when combined with other antiretroviral
      drugs. In addition, it is well tolerated with a good safety profile, and can be
      taken once or twice daily with no food restrictions. Trough plasma levels
      obtained with once or twice daily boosted fosamprenavir are above the mean
      protein-binding adjusted IC50 values for wild-type and PI-resistant virus. When
      given twice daily boosted, no significant pharmacokinetic (PK) interaction is
      seen with tenofovir, the nucleoside reverse transcriptase inhibitors (NRTIs),
      efavirenz or nevirapine, and there is no requirement for any dose adjustment.
      Interactions with other PIs are difficult to predict. A reduction in plasma
      amprenavir level is seen when fosamprenavir or amprenavir is combined with
      ritonavir-boosted lopinavir, saquinavir or tipranavir: reductions in lopinavir
      and saquinavir plasma levels are also seen. Various dosing strategies have been
      evaluated to overcome these negative interactions. With unboosted atazanvir, an
      increase in amprenavir levels is found. This article will focus on the
      pharmacokinetics of ritonavir-boosted fosampreanvir and review drug interactions
      with other antiretroviral (ARV) and non-ARV agents.

PMID- 15731741
TI  - Drug transporters relevant to HIV therapy.
AB  - Membrane transporters play a key role in the intestinal absorption, tissue
      distribution, cellular accumulation and renal excretion of anti-HIV drugs. A
      clear understanding of the individual roles of these transporters is, therefore,
      essential if we are to attempt to design new drugs and use drug combinations that
      are more clinically effective. This review attempts to provide an overview of
      those membrane transporters considered to be relevant to the disposition and
      effectiveness of nucleoside reverse transcriptase inhibitors (NRTIs), non
      nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors
      (PIs). However, we are still at an early stage in our understanding of these drug
      transporters and their interactions with anti-HIV drugs. Rapid progress in this
      area is essential if the therapeutic potential of anti-HIV drugs is to be fully
      exploited.

PMID- 15731742
TI  - Intracellular pharmacokinetics of antiretroviral agents.
AB  - Apart from fusion inhibitors, 'conventional' antiretrovirals such as nucleoside
      reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) and protease inhibitors (PIs) act on intracellular targets.
      Intracellular concentrations of these agents may be an important determinant of
      antiviral activity, and the pharmacokinetics of intracellular drug accumulation
      (including binding to cytosolic proteins, intracellular-free fraction, influx and
      efflux kinetics and intracellular drug metabolism) are likely to impact upon
      efficacy and toxicity. To date, intracellular drug accumulation has been poorly
      studied in vivo, due to methodological difficulties and the relatively large
      volumes of blood required. NRTIs require intracellular conversion to their active
      phosphorylated metabolites: interactions between these agents, or with other
      drugs may impact upon efficacy. PIs are metabolised by cytochrome P450 enzymes in
      gut and liver; some intracellular metabolism by P450 isoforms is also possible.
      PIs are also substrates for drug efflux transporters such as P-gp and MRP1. We
      have previously observed a hierarchy of intracellular accumulation of PIs, most
      probably related to physiochemical characteristics of these drugs such as
      lipophilicity and plasma protein binding. Comparatively, little is known about
      the intracellular pharmacokinetics of NNRTIs. These drugs probably do not
      accumulate inside cells to any significant degree. The study of intracellular
      pharmacokinetics of HIV drugs is central to investigating putative sanctuary
      sites where HIV may replicate with little selective pressure. However, stringent
      methodological procedures need to be applied, and techniques for measuring
      intracellular drug are in their infancy. Moreover, failure to differentiate
      between truly intracellular drug and drug bound to cell membranes render results
      difficult to interpret.

PMID- 15731744
TI  - Improving neurodevelopmental outcomes after neonatal herpes simplex virus
      infection.

PMID- 15731745
TI  - Neonatal distal femoral physeal fracture requiring closed reduction and pinning.
AB  - Neonatal physeal fracture of the distal femur is often difficult to diagnose.
      Timely and accurate diagnosis and appropriate therapy are critical in order to
      avoid permanent morbidity and dysfunction of the affected limb. We describe an
      infant in whom closed reduction and pinning were required in order to assure a
      good outcome.

PMID- 15731746
TI  - Intrauterine torsion of a testicular teratoma: a case report.
AB  - Neonatal testicular tumors and intrauterine testicular torsions are very rare.
      The presented case is the first describing intrauterine torsion of a descended
      testis with a teratomatous tumor. Immediately after birth, right hemiscrotal
      swelling was seen in a preterm male newborn. Surgical intervention showed
      extravaginal testicular torsion and a highly differentiated testicular teratoma
      with haemorrhagic infarction. The testis was removed (orchiectomy). Over a period
      of twelve months no signs of tumor recurrence were found. While being extremely
      rare, testicular tumors should be included in the differential diagnosis of
      neonatal scrotal swelling.

PMID- 15731747
TI  - Too much of a good thing? Epinephrine on trial!

PMID- 15731749
TI  - Old mice, new tricks.

PMID- 15731750
TI  - Mapping expression in randomized rodent genomes.

PMID- 15731751
TI  - Comparative epigenomics of leukemia.

PMID- 15731752
TI  - SWItching off methylated DNA.

PMID- 15731753
TI  - Dissecting dispensability.

PMID- 15731754
TI  - Dynamin in disease.

PMID- 15731757
TI  - A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal
      development caused by mutations in TGFBR1 or TGFBR2.
AB  - We report heterozygous mutations in the genes encoding either type I or type II
      transforming growth factor beta receptor in ten families with a newly described
      human phenotype that includes widespread perturbations in cardiovascular,
      craniofacial, neurocognitive and skeletal development. Despite evidence that
      receptors derived from selected mutated alleles cannot support TGFbeta signal
      propagation, cells derived from individuals heterozygous with respect to these
      mutations did not show altered kinetics of the acute phase response to
      administered ligand. Furthermore, tissues derived from affected individuals
      showed increased expression of both collagen and connective tissue growth factor,
      as well as nuclear enrichment of phosphorylated Smad2, indicative of increased
      TGFbeta signaling. These data definitively implicate perturbation of TGFbeta
      signaling in many common human phenotypes, including craniosynostosis, cleft
      palate, arterial aneurysms, congenital heart disease and mental retardation, and
      suggest that comprehensive mechanistic insight will require consideration of both
      primary and compensatory events.

PMID- 15731758
TI  - Mutations in the pleckstrin homology domain of dynamin 2 cause dominant
      intermediate Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous
      group of peripheral neuropathies. Different chromosomal loci have been linked
      with three autosomal dominant, 'intermediate' types of CMT: DI-CMTA, DI-CMTB and
      DI-CMTC. We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 to
      4.2 Mb in three unrelated families with CMT originating from Australia, Belgium
      and North America. After screening candidate genes, we identified unique
      mutations in dynamin 2 (DNM2) in all families. DNM2 belongs to the family of
      large GTPases and is part of the cellular fusion-fission apparatus. In
      transiently transfected cell lines, mutations of DNM2 substantially diminish
      binding of DNM2 to membranes by altering the conformation of the beta3/beta4 loop
      of the pleckstrin homology domain. Additionally, in the Australian and Belgian
      pedigrees, which carry two different mutations affecting the same amino acid,
      Lys558, CMT cosegregated with neutropenia, which has not previously been
      associated with CMT neuropathies.

PMID- 15731759
TI  - Pyrexia is a new thermal transient receptor potential channel endowing tolerance
      to high temperatures in Drosophila melanogaster.
AB  - Several transient receptor potential channels were recently found to be activated
      by temperature stimuli in vitro. Their physiological and behavioral roles are
      largely unknown. From a temperature-preference behavior screen of 27,000
      Drosophila melanogaster P-insertion mutants, we isolated a gene, named pyrexia
      (pyx), encoding a new transient receptor potential channel. Pyx was opened by
      temperatures above 40 degrees C in Xenopus laevis oocytes and HEK293T cells. It
      was ubiquitously expressed along the dendrites of a subset of peripheral nervous
      system neurons and was more permeable to K(+) than to Na(+). Although some pyx
      alleles resulted in abnormal temperature preferences, pyx null flies did not have
      significantly different temperature preferences than wild-type flies. But 60% of
      pyx null flies were paralyzed within 3 min of exposure to 40 degrees C, whereas
      only 9% of wild-type flies were paralyzed by the same stimulus. From these
      findings, we propose that the primary in vivo role of Pyx is to protect flies
      from high-temperature stress.

PMID- 15731760
TI  - MAGIC, an in vivo genetic method for the rapid construction of recombinant DNA
      molecules.
AB  - We describe a highly engineered in vivo cloning method, mating-assisted
      genetically integrated cloning (MAGIC), that facilitates the rapid construction
      of recombinant DNA molecules. MAGIC uses bacterial mating, in vivo site-specific
      endonuclease cleavage and homologous recombination to catalyze the transfer of a
      DNA fragment between a donor vector in one bacterial strain and a recipient
      plasmid in a separate bacterial strain. Recombination events are genetically
      selected and result in placement of the gene of interest under the control of new
      regulatory elements with high efficiency. MAGIC eliminates the need for
      restriction enzymes, DNA ligases, preparation of DNA and all in vitro
      manipulations required for subcloning and allows the rapid construction of
      multiple constructs with minimal effort. We show that MAGIC can generate
      constructs for expression in multiple organisms. As this new method requires only
      the simple mixing of bacterial strains, it represents a substantial advance in
      high-throughput recombinant DNA production that will save time, effort and
      expense in functional genomics studies.

PMID- 15731764
TI  - Understanding nuclear organization: when information becomes knowledge. Workshop
      on Nuclear Organization.

PMID- 15731765
TI  - Semi-rational engineering of a coral fluorescent protein into an efficient
      highlighter.
AB  - Kaede is a natural photoconvertible fluorescent protein found in the coral
      Trachyphyllia geoffroyi. It contains a tripeptide, His 62-Tyr 63-Gly 64, which
      acts as a green chromophore that is photoconvertible to red following (ultra-)
      violet irradiation. Here, we report the molecular cloning and crystal structure
      determination of a new fluorescent protein, KikG, from the coral Favia favus, and
      its in vitro evolution conferring green-to-red photoconvertibility. Substitution
      of the His 62-Tyr 63-Gly 64 sequence into the native protein provided only
      negligible photoconversion. On the basis of the crystal structure, semi-rational
      mutagenesis of the amino acids surrounding the chromophore was performed, leading
      to the generation of an efficient highlighter, KikGR. Within mammalian cells,
      KikGR is more efficiently photoconverted and is several-fold brighter in both the
      green and red states than Kaede. In addition, KikGR was successfully
      photoconverted using two-photon excitation microscopy at 760 nm, ensuring optical
      cell labelling with better spatial discrimination in thick and highly scattering
      tissues.

PMID- 15731767
TI  - The telomerase RNA component Terc is required for the tumour-promoting effects of
      Tert overexpression.
AB  - A role for the telomerase reverse transcriptase subunit (Tert) in tumorigenesis
      independent of telomere length is emerging. K5-Tert mice, which overexpress Tert
      in the skin, show increased tumorigenesis and faster wound healing than wild-type
      controls. Here, we demonstrate that the telomerase RNA component Terc is
      necessary to mediate these effects of Tert overexpression. In contrast to K5-Tert
      mice, K5-Tert mice in a Terc-deficient background, K5-Tert/Terc-/-, do not show
      increased tumorigenesis or increased wound healing compared with wild-type
      controls. Indeed, K5-Tert/Terc-/- mice show a reduction in tumour growth compared
      with Terc-/- controls, indicating an inhibitory effect of Tert overexpression in
      the absence of Terc. These results indicate that the tumour-promoting effects of
      Tert overexpression require the formation of Tert-Terc complexes. In addition, we
      show that the increased expression of Tert in the absence of Terc has an
      inhibitory effect on tumorigenesis, independently of telomere length and
      telomerase activity. These findings highlight Terc as a target for telomerase
      based anticancer therapies.

PMID- 15731766
TI  - Structural rearrangements in tubulin following microtubule formation.
AB  - Microtubules are essential cytoskeletal structures that mediate several dynamic
      processes in a cell. To shed light on the structural processes relating to
      microtubule formation and dynamic instability, we investigated microtubules
      composed of 15 protofilaments using cryo-electron microscopy, helical image
      reconstruction and computational modelling. Analysis of the configuration of the
      alpha beta-tubulin heterodimer shows distinct structural differences in both
      subunits, and illustrates that the tubulin subunits have different roles in the
      microtubule lattice. Our modelling data suggest that after GTP hydrolysis
      microtubules, adopt a conformational state somewhere between a straight
      protofilament conformation--as found in zinc-induced tubulin sheets--and an
      outward curved conformation--as found in tubulin-stathmin complexes. The tendency
      towards a curved conformation seems to be mediated mostly by beta-tubulin,
      whereas alpha-tubulin resembles a state more related to the straight structure.
      Our data suggest a possible explanation of dynamic instability of microtubules,
      and for nucleotide-sensitive microtubule-binding properties of microtubule
      associated proteins and molecular motors.

PMID- 15731768
TI  - ASPP1 and ASPP2 are new transcriptional targets of E2F.
AB  - The E2F family of transcription factors regulates the expression of a number of
      genes whose products are involved in cell cycle control, DNA replication and
      apoptosis. We show here that E2F-1 binds in vivo the promoters of ASPP1 and ASPP2
      genes, two activators of p53-mediated apoptosis, E2F-1, E2F-2 and E2F-3 all
      activate the isolated ASPP1 and ASPP2 promoters. Overexpression or deregulation
      of E2F-1 increased the expression levels of ASPP1 and ASPP2 mRNA and proteins.
      The identification of ASPP1 and ASPP2 genes as transcriptional targets of E2F
      provides another mechanism by which E2F cooperates with p53 to induce apoptosis.

PMID- 15731769
TI  - Abnormalities on the multifocal electroretinogram may precede clinical signs of
      hydroxychloroquine retino-toxicity.

PMID- 15731770
TI  - Corneal endothelial cell density in a normal Pakistani population.

PMID- 15731771
TI  - Glaucoma monitoring in patients with a 'pseudophakic cataract'.
AB  - PURPOSE: To assess potential problems in monitoring glaucoma status in
      pseudophakic patients in whom the intraocular lens (IOL) has undergone varying
      degrees of opacification. METHODS: Data was collected by retrospective review of
      the notes of such patients, who had received a hydrophilic acrylic IOL, SC-60B
      0UV, after primary cataract extraction by phacoemulsification. At first, among
      these, patients with glaucoma were identified and notes were reviewed to identify
      problems with patients in whom the IOL had undergone varying degrees of
      opacification. RESULTS: A total of 32 eyes with glaucoma were identified to have
      received the SC-60B-0UV IOL. Of these, 13 IOLs (40.6%) had undergone varying
      degrees of opacification. Eyes with the opacified IOLs showed decreased visual
      acuity (2.5 lines of Snellen acuity on average). For these eyes, visual field
      performance (as determined on automated field analyzers) and optic disc
      assessments were adversely affected giving a false impression of advanced
      glaucomatous field loss. CONCLUSION: In our experience, glaucoma monitoring is
      made comparatively more difficult in pseudophakic patients with cloudy IOLs.
      Problems are encountered during assessment of the glaucomatous optic disc due to
      poor view of the optic disc. On standard static automated visual fields, these
      opacified IOLs produce artefactual visual field defects making monitoring
      glaucoma and subsequent management more difficult.

PMID- 15731772
TI  - Clinical characteristics of cyclodeviation.
AB  - PURPOSE: To retrospectively evaluate the incidence of cyclodeviation among
      patients with diplopia and analyse the causative diseases and clinical
      manifestations of cyclodeviation. METHODS: The medical records of 266 consecutive
      patients of 15 years of age or older presenting with diplopia, who had undergone
      the Lancaster red-green test (LRGT) from January 2001 to December 2002, were
      retrospectively reviewed. The presence of cyclodeviation on LRGT, predisposing
      conditions, causative diseases, and clinical manifestations of cyclotropia were
      analysed. Cyclodeviation on the LRGT were compared with those from the Maddox
      double-rod test (MDRT) and fundus photography. RESULTS: A total of 63 (24%) out
      of 266 patients exhibited cyclodeviation on LRGT. Eight out of 63 patients with
      cyclodeviation on the LRGT complained of torsional diplopia. Superior oblique
      palsy (SOP) was the most common causative disease (42 patients), followed by skew
      deviation (six) and thyroid orbitopathy (three). Excyclodeviation was found in 57
      patients and incyclodeviation in four patients on the LRGT. The spontaneous
      recovery rate was 83% in patients of vascular origin and 17% of traumatic origin.
      Cyclodeviation with the MDRT and fundus photography showed good correlation with
      those obtained from the LRGT. There was no association of the amount of
      cyclotropia with the presence of torsional diplopia as well as with its recovery.
      CONCLUSION: In spite of the rare complaint of torsional diplopia, 24% of the
      patients with diplopia showed cyclodeviation on the LRGT. SOP was the most common
      causative disease. Most of the patients with cyclodeviation of a vascular origin
      showed spontaneous improvement.

PMID- 15731773
TI  - Meningococcal group B meningitis associated with a focal chorioretinitis.

PMID- 15731774
TI  - Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive
      squamous cell carcinoma of the uterine cervix.
AB  - Maspin is a serine protease inhibitor with tumor suppression activity. It is
      expressed in normal breast and prostate tissue but is downregulated or absent in
      breast and prostate tumors. Recent reports have shown that decreased expression
      is associated with a greater propensity for metastasis in oral squamous cell
      carcinomas. We know that some high-grade cervical intraepithelial neoplasia
      progress to invasive carcinomas while others either persist at the same degree of
      atypia or regress. The pattern of maspin expression in cervical intraepithelial
      neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive
      squamous cell carcinomas of the uterine cervix was studied to determine the
      relationship between the extent of maspin expression and the progression of
      cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases
      were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven
      cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous
      cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues.
      Immunoreactivity was scored semiquantitatively using a scale of 0-3. The sums of
      the scores of the different groups were compared using the Mann-Whitney U-test. A
      significant decrease in maspin scores was noted between cervical intraepithelial
      neoplasia-grade 3 vs invasive squamous cell carcinoma (P<0.005), microinvasive
      squamous cell carcinoma vs invasive squamous cell carcinoma (P<0.05), and
      cervical intraepithelial neoplasia-grade 3 vs tumor emboli (P<0.005). Although
      not statistically significant, scores of cervical intraepithelial neoplasia-grade
      3 associated with invasive squamous cell carcinoma were lower compared to that
      cervical intraepithelial neoplasia-grade 3 without invasive squamous cell
      carcinoma. These findings suggest that maspin likely plays a role in disease
      progression from in situ to invasive carcinoma. Virtual absence of maspin
      immunopositivity in tumor emboli indicates that maspin may also play a role in
      metastasis.

PMID- 15731775
TI  - Loss of mismatch repair protein immunostaining in colorectal adenomas from
      patients with hereditary nonpolyposis colorectal cancer.
AB  - Colorectal adenomas occur at younger age, at increased frequency and have a
      greater tendency for malignant transformation in patients with hereditary
      nonpolyposis colorectal cancer (HNPCC). We performed immunostaining for the
      mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 in 35 colorectal adenomas from
      26 patients with HNPCC and identified loss of immunostaining in 23/35 (0.66)
      adenomas. Loss of mismatch repair protein immunostaining was particularly
      frequent in large (>5 mm) (14/16) and proximally located (13/15) adenomas,
      whereas the gene mutated--MLH1 or MSH2--and the type of mutation did not seem to
      affect the results. We conclude that loss of mismatch repair protein
      immunostaining is detected at a lower rate in adenomas than in carcinomas
      associated with HNPCC. Adenomatous tissue can thus be used for immunostaining of
      mismatch repair proteins in clinical investigations of HNPCC, but whereas loss of
      immunostaining may pinpoint the gene affected and thereby guide mutation
      analysis, retained staining cannot exclude that the adenoma developed as part of
      the syndrome due to reduced sensitivity. However, the analysis has a greater
      chance of being informative if large and proximally located adenomas are
      selected.

PMID- 15731776
TI  - Type II collagen as specific marker for mesenchymal chondrosarcomas compared to
      other small cell sarcomas of the skeleton.
AB  - Mesenchymal chondrosarcoma is a rare, usually highly malignant chondrogenic
      neoplasm. The diagnosis of mesenchymal chondrosarcoma can be challenging, it
      nonetheless has important therapeutic and diagnostic implications. Thus, biopsies
      of mesenchymal chondrosarcomas without conspicuous cartilaginous differentiation
      cannot be safely distinguished from other small cell mesenchymal neoplasms such
      as Ewing's sarcoma and peripheral neuroendrocrine tumors, synovial sarcomas and
      hemangiopericytomas, because all of these neoplasms might show overlapping
      histological features, and so far, there have been no safe immunohistochemical
      markers available in order to differentiate these neoplasms. In our study on a
      large series of mesenchymal chondrosarcomas (n=30) and other small cell sarcomas
      (Ewing's sarcomas (n=12), synovial sarcomas (n=6), hemangiopericytomas (n=5),
      small cell osteosarcomas (n=3), and desmoplastic small round cell tumors (n=1)),
      we could establish the presence of type II collagen in the extracellular tumor
      matrix of the small cell areas of mesenchymal chondrosarcomas as a specific and
      sensitive marker to identify mesenchymal chondrosarcomas and to exclude other
      small cell neoplasms (except chondroblastic areas in small cell osteosarcomas).
      In contrast, the S-100 protein was less sensitive and vimentin and total collagen
      content unspecific for discriminating these neoplasms. Thus, the presence of type
      II collagen in the extracellular tumor matrix significantly facilitates the
      diagnosis of mesenchymal chondrosarcomas in the absence of histologically visible
      chondroid matrix formation.

PMID- 15731777
TI  - Alterations of protein 4.1 family members in ependymomas: a study of 84 cases.
AB  - Ependymomas are common pediatric and adult CNS malignancies with a wide biologic
      spectrum that is often hard to predict using classic prognostic variables. The
      molecular pathogenesis is also poorly understood and few reproducible genetic
      alterations have been identified. The most common genetic alteration has been the
      loss of the Protein 4.1 family member, NF2, predominantly in spinal ependymomas.
      In contrast, a pilot study suggested that 4.1B deletions might be more common in
      intracranial ependymomas. These findings prompted us to study Protein 4.1 family
      members (NF2, 4.1B, 4.1R, 4.1G) in a larger cohort of 84 ependymomas (51
      intracranial and 33 spinal; 11 WHO grade I, 43 grade II, 30 grade III).
      Fluorescence in situ hybridization was performed using NF2, 4.1B, 4.1R and 4.1G
      probes and immunohistochemical staining was performed in a subset using merlin,
      Protein 4.1B and Protein 4.1R antibodies. Additionally, frozen tissue from nine
      ependymomas (four intracranial and five spinal) was obtained for Western blot
      analysis for merlin, 4.1B and 4.1R expression. The majority of cases harbored one
      or more detectable genetic alterations, but we found that 4.1B gene deletions and
      4.1R loss of expression were statistically more common in the pediatric vs adult,
      intracranial vs spinal, and grade III vs grade I/II subsets (P-values of 0.038 to
      <0.001). Also, 4.1G deletions were seen in 11/27 (41%) patients who either died
      of disease or had residual/recurrent tumor vs 5/41 patients with no evidence of
      disease at last follow-up (P=0.009). We conclude that alterations of Protein 4.1
      family members are common in ependymal tumors and that specific alterations are
      associated with distinct clinicopathologic subsets.

PMID- 15731778
TI  - Phenotypic alterations in Rb pathway have more prognostic influence than p53
      pathway proteins in oral carcinoma.
AB  - The two well-defined pathways that are shown to be prominently altered in a
      variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb
      genes. The present study is undertaken to find the pathway that is more altered
      in oral carcinoma at protein level, with special emphasis on its prognostic
      significance. The expression pattern of key molecules of the Rb and p53 pathways,
      such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker
      PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical
      technique. The expression index of these molecules and various
      clinicopathological factors were statistically correlated with treatment end
      points to assess its prognostic efficacy after following up these patients up to
      a maximum of 48 months with a median of 23 months. Rb pathway proteins, Rb
      (P=0.016), cyclin D1 (P=0.0001) and p16 (P=0.012) showed significant association
      with disease-free survival, and p16 (P=0.041) and cyclin D1 (P=<0.0001) with the
      overall survival. Among p53 pathway proteins studied, only p53 expression index
      showed association with both disease-free survival and overall survival.
      Multivariate analyses confirmed that the biological variables, cyclin D1 and p16
      and the clinical variable, 'stage of disease' were independent predictors of
      disease-free survival and overall survival. Subgrouping of the patients on the
      basis of p16 and cyclin D1 expression revealed that the subgroup having
      downregulation of p16 and overexpression of cyclin D1 exhibited the worst disease
      free survival and overall survival compared to the other subgroups. The present
      data showed that disabling of the Rb and p53 pathways were frequent events in
      oral carcinoma. The study also demonstrated that the Rb pathway proteins are
      comparatively more important than p53 pathway proteins for the prognostication of
      oral carcinoma patients. The combined evaluation of p16 and cyclin D1 in oral
      carcinoma could identify a group of patients with the worst survival who might
      therefore need alternate or more intense treatment strategies.

PMID- 15731793
TI  - Out-of-hours emergency dental services--evaluation of the first year of a pilot
      project in Fife.
AB  - The Scottish Executive Health Department approved funding in 2001 for Fife NHS
      Board to pilot an integrated model of out-of-hours dental services based upon a
      dental nurse-led triage system during the evenings, weekends and some public
      holidays. After one year of the pilot project the activity was evaluated by
      analysing the triage database. Nearly 4,000 calls were received--Fridays and
      Saturdays were the most popular days to telephone which resulted in nearly half
      of all callers being referred to an emergency weekend clinic. Thirty-nine percent
      of callers received advice only or were advised to contact their own dentist
      during working hours. A further 12% who were not registered with a dentist
      (n=479) were offered a next-day appointment with a dentist in their area--around
      half of these callers subsequently attended for an appointment. Only two out of
      every 100 callers were deemed to require emergency out-of-hours attention and
      were referred to oral surgery staff in a local hospital.

PMID- 15731794
TI  - Eruption of teeth in the nose following trauma to the primary and permanent
      dentitions.
AB  - Oro-facial trauma is common and forms a large component of any maxillofacial
      service workload. Even minor trauma can result in significant oro-facial and
      dental injury. This report reinforces the importance of a careful dental history
      and thorough examination, particularly when teeth remain missing after initial
      inspection. Other anatomical sites should be considered to ensure they do not
      contain traumatically displaced teeth. These two case reports show the late
      presentation of incisor teeth in the nasal cavity following dentoalveolar trauma.

PMID- 15731795
TI  - Management of extensive dentigerous cysts.
AB  - Dentigerous cysts are usually easy to treat when small. However, extensive cysts
      are more difficult to manage requiring cyst enucleation and extraction of
      associated teeth. We advocate the use of assessment criteria to dictate the
      treatment modality indicated in each individual case such as cyst size and site,
      patient age, the dentition involved, and the involvement of vital structures.
      Cyst enucleation without extraction of the impaction, and decompression are two
      treatment modalities indicated in growing children and adolescents to salvage the
      involved dentition.

PMID- 15731796
TI  - Automatic external defibrillators--time for a change?
AB  - Defibrillation is the definitive treatment for cardiac arrest. Until relatively
      recently the use of defibrillators was restricted to medical staff and
      paramedics. The development of automatic external defibrillators (AEDs) now means
      that this life-saving equipment may be used by anyone with a short period of
      training. This article will review the patho-physiology of cardiac arrest, the
      use of AEDs and their significance to the dental team. A medical emergency could
      happen at any time in the dental practice. Cardiac arrest is the most serious
      emergency that can occur. Whilst life-threatening incidents are very rare, the
      dental team requires to be trained in the management of a cardiac arrest.

PMID- 15731803
TI  - Dependant factors.

PMID- 15731804
TI  - Good dental care.

PMID- 15731805
TI  - Drug users: oral health-related attitudes and behaviours.
AB  - AIM: Explore oral health-related attitudes and behaviours of drug users. DESIGN:
      Qualitative study using focus groups and semi-structured interviews. SETTING:
      Facilities for treatment and recovery of drug users in South London.
      PARTICIPANTS: Twenty-six male and 14 female recovering drug users. RESULTS:
      Participants described many changes in lifestyle associated with drug use
      including the physical effects of drugs, dietary habits, organisational and time
      constraints and unfavourable social conditions, which were not conducive to oral
      health. There was considerable health consciousness. They associated general
      health problems and problems with teeth, gums and oral soft tissues to both
      direct and indirect effects of drug use. Use of dental services was inhibited by
      low priority for oral health relative to the need to obtain and use drugs,
      experientially induced fear of dentists, the acceptability of dental services,
      needle-phobia, ability to self-medicate and organisational factors in their
      lifestyles. CONCLUSIONS: The lifestyles of drug users may contribute to oral
      health problems and low use of services. Drug users therefore comprise a group
      with special dental needs and need greater access to dental care than most
      people. Much of this care could be provided in general practice where appropriate
      dental care can contribute to recovery from drug use.

PMID- 15731806
TI  - An investigation of therapeutic antibiotic prescribing for children referred for
      dental general anaesthesia in three community national health service trusts.
AB  - OBJECTIVE: To investigate antibiotic prescribing for paediatric dental patients
      requiring general anaesthesia. DESIGN: A prospective clinical study of children
      referred for dental treatment under general anaesthesia. METHOD: Information was
      collected by way of a two-stage questionnaire for children attending three
      community NHS trusts for dental extractions under general anaesthesia between
      July 2001 and January 2003. RESULTS: A total of 360 questionnaires were analysed.
      There was wide variation in the waiting times (0-278 days) between referral and
      treatment under general anaesthesia. Most children (53%) attended with dento
      alveolar abscess, 46% with caries only and 1% for orthodontic extractions.
      Antibiotics were prescribed to 52% of patients with an abscess and 32% with
      caries only. Only 16% of patients presented with moderate to severe pain, 5.5%
      with diffuse swelling and 12% with a raised temperature. Antibiotics were
      prescribed for patients with diffuse swelling (63%) and raised temperature (50%)
      but also for patients with pain only (39%) and localised swelling (52%).
      Amoxicillin was the most frequently prescribed antibiotic (82%), with wide
      variation in all antibiotic regimens. CONCLUSION: This study provides evidence of
      inappropriate prescribing of antibiotics to children referred for treatment under
      general anaesthesia with wide variations in the regimens employed. There was no
      conclusive evidence that long waiting times for definitive treatment influenced
      antibiotic prescribing. In some areas the delay for definitive treatment for this
      group of vulnerable patients was unacceptably long.

PMID- 15731807
TI  - Developing dental education in primary care: the student perspective.
AB  - A pilot outreach course in restorative dentistry based in community clinics began
      in 2001. As part of the evaluation, 48 fourth year students completed a
      questionnaire about their opinions of the new course, and about restorative
      dentistry clinics in the dental hospital. Time management was the most frequently
      mentioned gain from outreach. In relation to the dental school, students most
      often saw the specialised teaching staff as a gain. Outreach was equally or more
      important for students' confidence in clinical diagnosis of dental caries,
      treatment planning, direct restorations, communicating with patients, and
      managing patients, time, and resources. The dental hospital was equally or more
      important for their confidence in the diagnosis of periodontal disease, root
      planing, crowns, bridges, dentures, and communicating effectively with laboratory
      staff. Patients in outreach were seen as different from those at the dental
      hospital because they were unselected, and had different treatment needs. Meeting
      course requirements was the most frequent concern about outreach. In relation to
      the dental hospital, students were most often concerned about the quality of
      teaching and support available. Outreach and the dental hospital provided
      complementary experiences and the new course met its educational objectives.

PMID- 15731826
TI  - Total selenium concentrations in canine and feline foods commercially available
      in New Zealand.
AB  - AIMS: To determine the total selenium concentrations in petfoods commercially
      available in New Zealand and to establish whether these meet the current minimum
      recommended requirements of selenium in foods for cats and dogs. METHODS: Samples
      (n=89) from petfoods commercially available in New Zealand were analysed for
      total selenium concentration using a fluorometric method. Data, expressed on a
      dry matter (DM) basis, were analysed according to petfood type (dog or cat, and
      wet or dry), predominant flavour (chicken, seafood, chicken and seafood, beef,
      meat mix, other), manufacturer and country of manufacture. RESULTS: Fifty percent
      of petfoods purchased for this study were manufactured in Australia, and the
      remainder were produced in the United States of America (USA), New Zealand or
      Thailand. Mean total selenium concentrations were similar (0.61-0.80 mg/kg DM) in
      petfoods produced in Australia, New Zealand and the USA, but higher (mean 3.77
      mg/kg DM; p<0.05) in petfoods produced in Thailand. Petfoods produced in
      Australia, New Zealand and the USA contained a variety of predominant flavours,
      whereas petfoods from Thailand contained only seafood flavour. Seafood-based
      flavours had the highest selenium concentrations in both cat and dog foods. Wet
      and dry dog foods had similar concentrations of selenium to dry cat foods, but
      wet cat foods had higher and more variable concentrations of selenium than these
      others (p<0.05). The mean selenium concentrations in cat and dog foods were 1.14
      and 0.40 mg/kg DM, respectively, and there were no significant differences
      between manufacturers. CONCLUSIONS: Selenium concentrations in commercial
      petfoods sold in New Zealand appeared to meet recommended dietary requirements,
      although the range of concentrations was highly variable. Whether these
      recommendations are adequate for the maintenance of optimal health in cats and
      dogs has yet to be determined. CLINICAL RELEVANCE: Overt selenium deficiency
      disorders are unlikely in dogs and cats in New Zealand fed commercial petfoods
      unless the bioavailability of selenium in particular petfoods is low.

PMID- 15731827
TI  - The effects of stationary periods and external temperature and humidity on
      thermal stress conditions within sheep transport vehicles.
AB  - AIM: To identify the contributions of stationary periods and external climatic
      environments to thermal stress conditions for sheep on livestock transport
      vehicles during journeys in summer. METHODS: Two livestock transport vehicles
      carrying sheep, operating under commercial conditions in New Zealand, were
      monitored during February and March 2002. Temperature and humidity were logged in
      five pens inside each vehicle, as well as externally. From these data, the
      temperature-humidity index (THI) was calculated. Global positioning equipment was
      used to log the location of the vehicle and whether it was moving or stationary.
      Regression analysis was used to identify factors that made a significant
      contribution to the THI within the vehicle. Regression models included the
      effects of vehicle, journey, initial ambient temperature or THI, pen position and
      duration of each stationary period. RESULTS: The THI in the livestock pens
      generally increased when vehicles were stationary. The highest THI value (95) was
      recorded in a vehicle on an enclosed deck of a Cook Strait ferry. Ambient
      conditions, the initial THI of a pen, and duration of the stationary period were
      all significant contributors to increases in the THI. Some increases in the THI
      occurred in stationary vehicles despite ambient conditions being mild, suggesting
      that lack of airflow was a critical factor. During stationary periods, 34% of THI
      readings exceeded 75, and, on average, the THI increased by 0.16 for every minute
      of a stationary period. CONCLUSIONS: Increases in the THI that could be
      detrimental to the welfare of sheep could occur on stationary sheep transport
      vehicles at most daytime ambient temperatures during summer. For a given stocking
      density and vehicle design, the THI of a pen increased in proportion to the
      duration of the stationary period. Mild ambient conditions (<25 degrees C)
      provided some protection against excessive THI increases if the duration of the
      stop was limited, but drivers are best advised to park their vehicles where there
      is airflow, and to minimise the duration of stops where possible. Livestock
      transport vehicles during summer should not be placed on enclosed ferry decks
      where airflow is absent or minimal.

PMID- 15731828
TI  - Impact of iodine supplementation of dairy cows on milk production and iodine
      concentrations in milk.
AB  - AIM: To determine the effect of iodine supplementation on milk production and
      iodine concentrations in milk for pasture-fed, seasonally calving dairy cows.
      METHODS: The study was run over two consecutive seasons on the same dairy farm.
      In Trial One, 294 Friesian dairy cows were either untreated or injected
      intramuscularly three times with iodised oil (2,370 mg iodine/dose) at the start
      of lactation (Day 1) and at about 100-day intervals thereafter. Iodine
      concentrations in milk were determined prior to each injection on Days 1, 98 and
      210, and milk, fat and protein yields measured on Days 43, 98, 176 and 238. In
      Trial Two, 234 Friesian dairy cows were either untreated or injected
      intramuscularly with iodised oil (2,370 mg iodine/dose) in early lactation (Day
      1) and 99 days later. Iodine concentrations in milk were determined prior to
      treatment on Days 1, 55 and 161. Serum thyroxine (T4) and triiodothyronine (T3)
      concentrations were determined in the latter two samples and milk, protein and
      fat yields were determined on Days 25, 119, 182 and 221. In both trials, pasture
      was sampled at 1- or 3-monthly intervals and iodine concentrations in herbage
      measured. RESULTS: Iodine concentrations in pasture averaged 0.24 mg/kg dry
      matter (DM) in both seasons and varied little over the experimental period.
      Iodine concentrations in milk from unsupplemented cows were <20 microg/L in both
      trials. Three iodine injections at about 100-day intervals increased iodine
      concentrations in milk to 58 microg/L for at least 98 days after each treatment.
      Two iodine injections at about 100-day intervals raised milk iodine
      concentrations to 160 microg/L and 211 microg/L at least 55 days after each
      treatment, but had no effect on serum thyroid hormone concentrations. Iodine
      supplementation had no significant effect on milk, milkfat or milk protein yield.
      CONCLUSIONS: Pastures in New Zealand that contained 0.24 mg iodine/kg DM appeared
      to provide an adequate iodine intake for dairy cows. Intramuscular injections of
      iodine resulted in significant increases in iodine concentrations in milk.
      CLINICAL SIGNIFICANCE: Increasing iodine concentrations in milk via intramuscular
      injection of iodine could provide a method for significantly increasing iodine
      intakes of humans, in particular, children.

PMID- 15731829
TI  - Surveillance of wildlife for Mycobacterium bovis infection using culture of
      pooled tissue samples from ferrets (Mustela furo).
AB  - AIM: To compare culture results of homogenates of pooled lymph nodes from
      individual ferrets with and without macroscopic lesions of bovine tuberculosis
      for the presence of Mycobacterium bovis, and to determine whether homogenates
      from 10-30 ferrets could be combined and cultured without loss of sensitivity as
      a possible method for improving cost-effectiveness of surveillance for M. bovis
      infection in wildlife populations. METHODS: Numbers of colony forming units (cfu)
      of M. bovis present in cultures of homogenates of pooled lymph nodes from
      individual ferrets known to be infected and having no visible lesions (NVL) or
      macroscopic lesions consistent with bovine tuberculosis were determined.
      Prevalences of M. bovis infection in populations of ferrets in the Marlborough
      region of the South Island of New Zealand were determined by culturing
      homogenates of pooled lymph nodes from individual animals. Samples from
      homogenates from North Canterbury were combined to form pools representing 10, 20
      and 30 animals and also cultured for M. bovis. RESULTS: Fewer M. bovis cfu were
      isolated from ferrets with NVL (mean=0.77 log10) compared with ferrets with
      macroscopic lesions (mean=3.22 log10; p<0.05). The mean prevalence of infection
      in eight different surveys involving 427 ferrets from the Marlborough region was
      18% (range 8-44%), which included a small number of animals with macroscopic
      lesions of tuberculosis. Pooling of samples from up to 30 different ferrets with
      NVL did not reduce the sensitivity of detecting M. bovis infected populations.
      CONCLUSION: Culturing of pools of lymph node samples detected a significant
      proportion of M. bovis-infected ferrets that would otherwise have gone unnoticed
      based on samples that had only macroscopic lesions. Culturing of samples pooled
      from up to 30 different ferrets could provide significant cost savings in surveys
      of wildlife for the presence of M. bovis infection without any apparent loss of
      sensitivity.

PMID- 15731830
TI  - Diagnosis and surgical management of ureteral calculi in dogs: 16 cases (1990
      2003).
AB  - AIMS: To examine the clinical signs, laboratory and radiographic findings,
      surgical technique, ureterolith composition, and post-operative outcomes in dogs
      managed surgically for ureterolithiasis to determine whether surgical removal of
      ureteroliths in dogs resulted in a positive clinical outcome. METHODS: The
      medical record database of a university veterinary hospital in Pennsylvania, USA,
      was searched for dogs that underwent surgery to remove obstructive ureteral
      calculi between 1990 and 2003. Records were reviewed for signalment, clinical
      history and examination findings, radiographic and laboratory test results,
      surgical technique, and ureterolith analysis. Follow-up information was obtained
      from telephone interviews with owners or referring veterinarians, or by reviewing
      the medical record of subsequent hospital visits. RESULTS: Sixteen dogs were
      included in this study; ten were neutered females, two intact females and four
      castrated males. Abdominal radiography revealed ureteral calculi in 14/16 dogs,
      renal calculi in 8/16, cystic calculi in 8/16, urethral calculi in 1/16,
      renomegaly in 6/16 and renal mineralisation in 5/16. Ureterolith type included
      struvite in six dogs, calcium oxalate in five, calcium phosphate in one, and a
      mix of struvite, calcium phosphate and calcium oxalate in another. Compared to
      dogs with non-struvite ureteroliths, those with struvite ureteroliths had a
      higher pre-operative white blood cell (WBC) count (25.6, SD 7 vs 17.6, SD 6 x 103
      cells/mul; p=0.046), and were more likely to have a purulent discharge from the
      ureteral incision noted at the time of surgery (p=0.015). Following discharge,
      14/16 dogs were re-evaluated. Median survival time was 904 days (range 2-1,876).
      Two dogs required additional surgery on the urinary tract. Four dogs died or were
      euthanised because of azotaemia and clinical signs related to the urinary system
      or non-specific signs of illness (vomiting, lethargy) at 8, 90, 333 and 904 days
      post-operatively. CONCLUSIONS: Surgical management of ureteroliths was successful
      and resulted in good long-term survival in the majority of dogs examined in this
      small study population. Similar proportions of calcium oxalate and struvite
      ureteroliths were identified. CLINICAL RELEVANCE: The use of the ureteral surgery
      may increase as the frequency of diagnosis of ureteroliths in dogs increases.

PMID- 15731831
TI  - Detection and molecular characterisation of bovine polyomavirus in bovine sera in
      New Zealand.
AB  - AIM: To investigate the prevalence of bovine polyomavirus (BPyV) DNA in
      commercial batches of bovine serum products, cell lines and cattle in New Zealand
      and to characterise the viral DNA detected. METHODS: Two nested polymerase chain
      reaction (PCR) assays were applied to detect BPyV in bovine sera. One was used to
      screen for the VP1 gene of BPyV DNA in: 140 batches of commercial bovine serum
      products, including 66 batches of fetal bovine serum (FBS), 34 batches of calf
      serum, and 40 batches of adult bovine serum (ABS)/plasma; 112 individual adult
      bovine sera; and 16 cell lines of various species origin. Fifty batches of serum
      samples were also tested, using the second nested PCR assay that screened for the
      Large T gene. Restriction fragment length polymorphism (RFLP) was conducted with
      36 PCR products amplified from the VP1 gene of BPyV using EcoRI. Five selected
      VP1 PCR products were subjected to DNA sequencing and phylogenetic analysis.
      RESULTS: BPyV DNA was detected in 46 (70%) batches of FBS, 11 (32%) batches of
      calf sera and two (5%) batches of ABS/plasma, an overall prevalence of 42%. None
      of 112 adult bovine sera was BPyV-positive. RFLP analysis demonstrated a uniform
      digestion pattern in the majority (31/36) of amplicons tested, while the
      remaining PCR amplicons did not show enzyme cleavage. Sequence analysis of the
      PCR products (a 263 base pair (bp) fragment of the VP1 gene) obtained from five
      batches of FBS showed 96.2-98.9% homology to that of published sequences of BPyV.
      CONCLUSION: BPyV is a frequent contaminant of commercial bovine serum in New
      Zealand. The incidence of BPyV in adult bovine serum products is much lower than
      in FBS and calf serum. Genomic variations exist among different viruses. The
      clinical significance of the high prevalence of BPyV DNA in bovine serum products
      is yet to be determined.

PMID- 15731832
TI  - The effect of copper-amended fertiliser and copper oxide wire particles on the
      copper status of farmed red deer (Cervus elaphus) and their progeny.
AB  - AIM: To determine changes in serum and liver copper concentrations in postnatal,
      weaner, yearling, and mature deer after grazing pasture topdressed with copper
      (Cu) at two rates of application of copper sulphate (CuSO4(.)5H2O), and following
      oral administration of copper oxide (CuO) wire particles to some of the deer.
      METHODS: In mid-March 2000 (Year 1), 1.1-ha paddocks (two/treatment) of
      ryegrass/white clover pasture received either 0 (Control), 6 (Low) or 12 (High)
      kg CuSO4(.)5H2O /ha applied with 250 kg potash superphosphate/ha. They were
      grazed by 4-month-old red deer hinds (n=11/treatment) from mid-April 2000 until
      early March 2001. In mid-March 2001 (Year 2), the pastures were topdressed again
      as for Year 1, and the original hinds, now yearlings which had grazed as a single
      group between studies, were returned to their respective treatments in mid-April
      2001 and remained on the trial until mid-March 2002. They were mated during
      April/May. The pastures were also grazed by pregnant mature hinds (n=8/treatment)
      from mid-May 2001. As the Cu status (i.e. liver Cu concentration) of the yearling
      hinds on the pasture treated with 6 kg CuSO4(.)5H2O/ha was not significantly
      different from the untreated animals, in late July 2001 the yearling and mature
      deer on this treatment were treated orally with 10 g CuO wire particles. The
      mature hinds calved in November and the yearling hinds in December. Pasture
      samples were collected at about monthly intervals to determine concentrations of
      Cu and other minerals. In Year 1, liver biopsies and blood samples were collected
      at 4-6-weekly intervals for determination of Cu concentrations. In Year 2,
      samples were collected similarly at 6-12-weekly intervals. Liver biopsies and
      blood were also collected from progeny, along with milk from their dams.
      Liveweights were determined at 3-7-monthly intervals, as well as data on
      calving/mortality rates. RESULTS: Pasture Cu concentrations before the
      application of CuSO4(.)5H2O were 6-9 mg Cu/kg dry matter (DM) and remained at
      this level in the untreated Control paddocks throughout the study. In Year 1, 28
      days after treatment, pasture Cu concentration was 25 and 35 mg Cu/kg DM for the
      Low and High treatments, respectively; while at the same time for the same
      treatments in Year 2 it was 20 and 60 mg/kg DM, respectively. A second 60 mg
      Cu/kg DM peak also occurred on Day 85 in Year 2 with the High treatment. The
      pasture Cu concentration returned to 6-9 mg/kg DM, and there were no differences
      between treatments at Days 80 and 150 in Years 1 and 2, respectively. In Years 1
      and 2, the Low treatment had no significant effect on the Cu status of the weaner
      and yearling hinds, respectively, when compared with that of animals grazing the
      untreated Control pastures. Weaner (Year 1) and yearling (Year 2) deer on the
      High treatment had significantly higher mean serum and liver Cu concentrations in
      the late winter and spring period when compared with those on untreated Control
      pastures. CuO wire particles increased the mean serum Cu concentration at Days 60
      and 180, and liver Cu concentration at Day 60, in yearling hinds. A similar
      effect was observed in mature hinds. Regardless of Cu treatment, the liver Cu
      concentration of the 1-4-week-old progeny was markedly greater (p<0.001) than
      that of their dams, and then decreased significantly until weaning in March. In
      progeny of treated yearling hinds, but not mature hinds, serum and liver Cu
      concentrations were significantly higher (p=0.013) than progeny of untreated
      dams. CONCLUSION: Topdressing pastures with CuSO4(.)5H2O at a rate of 12 kg/ha,
      but not 6 kg/ha, in mid-March was effective in increasing the Cu status of
      weanling hinds; while pastures topdressed with 12 kg CuSO4(.)5H2O /ha in mid
      March and dosing hinds with 10 g CuO in late July were effective in increasing
      the Cu status of pregnant hinds, and in the case of the yearling hinds,
      significantly improved the Cu status of their progeny from birth to weaning.

PMID- 15731833
TI  - Reproductive performance of beef cow herds in New Zealand.
AB  - AIM: To describe the reproductive performance of beef cow herds in New Zealand
      and to develop reference ranges for assessing the reproductive performance of
      individual herds from in-calf rates, that take into account variation in the
      length of mating periods. METHODS: Veterinary practices throughout New Zealand
      involved in beef cattle work were asked to collect reproductive data from
      seasonally calving beef cow herds mated in the spring of 2001 through to the end
      of summer of 2002. An estimate of conception rate (termed calculated conception
      rate: CCR) was determined for each herd, assuming that the conception rate was
      constant for each 21-day interval of the mating period. The algebraic
      relationship between CCR and in-calf rate at pregnancy testing was defined for
      mating periods of different durations and, therefore, given the in-calf rate and
      the duration of the mating period, a CCR could be determined for each herd.
      Expected pregnancy rates were recalculated from CCR data for a range of mating
      period durations to produce a look-up table for assessing herd reproductive
      performance. Reproductive data describing regional differences in in-calf rates
      and CCRs, bull:cow ratios, breed characteristics, start dates of mating and
      durations of mating periods were summarised. The effect of study variables in
      explaining CCRs was examined using a general linear model (GLM). RESULTS: Data
      were collected from 1,005 beef cow herds distributed throughout New Zealand. The
      median in-calf rate for all herds was 91%, the lower quartile was < or =88% and
      the upper quartile > or =94%. The mean CCR for herds with complete reproductive
      data (862) was 55% (SD 11), the lower quartile was < or =48% and upper quartile >
      or =61%. Median in-calf rates for 2-year-old heifers (mated at approximately 15
      months of age), 3-year-old heifers (mated at approximately 27 months of age), and
      mixed-age cows were 90%, 91% and 92%, respectively. The study variables that
      accounted for significant variation in breeding group CCR in a multivariate GLM
      were 'region' (p<0.01) and 'date mating commenced' (<0.01). The adjusted R2 for
      the model was 0.055. CONCLUSIONS: The reproductive reference range produced
      provides veterinarians and herd managers with a quantitative method for assessing
      reproductive performance of beef cow herds compared with industry averages, from
      in-calf rates at the time of pregnancy testing and durations of mating periods.

PMID- 15731834
TI  - Investigation of bovine venereal campyloacteriosis in beef cow herds in New
      Zealand.
AB  - AIMS: To determine regional prevalences of beef cow herds in New Zealand positive
      for Campylobacter fetus subsp venerealis antibodies in samples of vaginal mucus
      tested using an immunoglobulin (Ig) A enzyme-linked immunosorbent assay (ELISA),
      and to examine the suitability of the IgA ELISA for detecting infection with C.
      fetus subsp venerealis under field conditions in New Zealand. METHODS: Vaginal
      mucus samples (n=1,230) collected from beef cow herds (n=125) throughout New
      Zealand (approximately 10 samples/herd) were tested for antibodies to C. fetus
      subsp venerealis using an IgA ELISA. Test results were compared between herds
      classified as having low, medium and high fertility based on pregnancy test
      results interpreted in relation to the duration of the mating period used. In
      addition, a small number of samples were collected from dairy cows that were
      mated using artificial insemination (AI) and had no contact with breeding bulls.
      The influence of putative risk factors for the spread of venereal disease and the
      effect of sample quality on the status of herds according to test results was
      assessed using multivariate logistical regression. Preputial washings from 54
      bulls from nine herds classified as low fertility in which mucus samples from >
      or =3 cows were IgA antibody-positive were cultured for the presence of
      Campylobacter spp, and isolates of C. fetus subspecies were characterised using a
      polymerase chain reaction (PCR) test. RESULTS: One or more mucus samples was
      positive to the IgA ELISA in 70% of all herds tested. The prevalence of IgA
      antibody- positive individuals was >20% in most regions of New Zealand and did
      not differ significantly for cows from herds classified as high, medium or low
      fertility (28%, 26% and 23%, respectively; p=0.39). No relationship was found
      between mucus antibody status and age of breeding group, herd size, herd
      fertility, number of herds that female replacements or breeding bulls were
      sourced from, whether a serving ability test (SAT) was used to assess bulls, or
      the quality of samples submitted to the laboratory. Campylobacter fetus subsp
      venerealis was not cultured from any of the 54 bulls sampled. Four other species
      of Campylobacter and related organisms were cultured, viz Arcobacter
      cryaerophilus, Campylobacter jejuni, Campylobacter fetus subsp fetus and
      Helicobacter cinaedi. CONCLUSIONS: The specificity of the IgA ELISA as a
      diagnostic test for C. fetus subsp venerealis was found to be unsatisfactory
      under New Zealand conditions. It is possible that an immunological response by
      cows to Campylobacter species other than C. fetus subsp venerealis caused cross
      reactivity in the IgA ELISA. The results do not support the hypothesis that C.
      fetus subsp venerealis is widespread in New Zealand.

PMID- 15731836
TI  - Profiling the New Zealand Thoroughbred racing industry. 1. Training, racing and
      general health patterns.
AB  - AIM: To describe patterns in training, racing, and general health in a population
      of Thoroughbred racehorses in New Zealand. METHODS: A longitudinal study was
      designed to collect data on horses training under the care of 20 selected
      trainers from 20 different stables and five regional training venues in the mid
      to lower regions of the North Island. Data were collected from trainers at
      approximately monthly intervals between October 1997 and July 2000, and
      electronic data containing race and trial results for all starts in New Zealand
      for the same time period were obtained from New Zealand Thoroughbred Racing
      (NZTR). Summary statistics were used to describe patterns present in the data.
      Horse training days and study days were used as the denominator horse-time-at
      risk for incidence rate estimations, and counts of horses and events used to
      derive proportions and cumulative incidence estimates. Simple statistical
      comparisons were completed using parametric and non-parametric procedures.
      RESULTS: Twenty trainers provided information on 1,571 horses, 554,745 horse
      study days, and 9,963 starts in official trials or races. Males comprised 50.2%
      of all horses. Although females contributed more study days for 2-, 3- and 4-year
      olds, males contributed more study days in horses aged > or =5 years. Horses
      spent an average of 71% of their time in training and the remaining 29% in spell
      periods. Duration of training preparations and spell periods was associated with
      horse age and the reason for a spell. Most horses began a training preparation
      doing slow work and then progressively advanced to a first start by 68 days after
      the start of a training preparation. Incidence rate estimates for starts,
      training days to first start, and training days between successive starts in the
      same preparation, are presented. Horses completed 2.5 starts per 100 training
      days with a median of 17 days between successive starts for the same horse.
      CONCLUSION: This study provides summary information on training, racing and
      general health patterns in Thoroughbred racehorses in the North Island of New
      Zealand. Although limited to simple comparisons and descriptive statistics, these
      results may contribute to the identification and prioritization of issues facing
      the racing industry in New Zealand.

PMID- 15731835
TI  - Multivariate analysis of risk factors for feline hyperthyroidism in New Zealand.
AB  - AIM: To search for putative risk factors for feline hyperthyroidism in New
      Zealand, using a case-control study. METHODS: A questionnaire-based case-control
      study involving the owners of 375 cats in New Zealand (125 hyperthyroid cats, 125
      randomly selected control cats, and 125 age- and sex-matched control cats) was
      conducted to examine associations between potential risk factors and occurrence
      of feline hyperthyroidism. Data were collected between December 1996 and February
      1998, relative to cat and owner demography and medical history, cats' indoor and
      outdoor environments, and cats' diets. A range of statistical techniques was
      employed to analyse the data, including descriptive analyses, univariate logistic
      regression for each variable and multivariate stepwise forward logistic
      regression. RESULTS: Multivariate analysis revealed that affected cats were more
      likely to be female (odds ratio (OR)=3.3; 95% confidence interval (CI)=1.2-9.0)
      and older than unaffected random control cats. Purebred cats were at a much lower
      risk of being diagnosed as hyperthyroid than were domestic short- and long-haired
      cats (OR=0.01; 95% CI=0.001-0.20). If more than one cat was present in a
      household, hyperthyroidism was less likely to be identified (OR=0.15; 95% CI=0.05
      0.44) compared with single-cat households. Hyperthyroid cats were 6.6 times more
      likely (95% CI=1.8-23.9) to be reported to sleep predominantly on the floor than
      control cats. Cats whose bedding was regularly treated with anti-flea products
      appeared to be at a considerably higher risk for hyperthyroidism (OR=57.6; 95%
      CI=3.8-->200); and, to a lesser extent, so were cats living in households where
      fly sprays were reported to be used regularly (OR=3.3; 95% CI=1.2-9.3). The
      interaction between drinking water from puddles and regular use of organic garden
      fertilisers, such as compost or animal manure, was associated with a 5.3-fold
      (95% CI=1.1-25.6) increase in the risk of cats being diagnosed with the disease.
      Hyperthyroid cats were twice as likely (95% CI=0.3-12.9) to have eaten at least
      half of their daily food requirements as canned commercial cat food compared with
      unaffected cats. Cats exposed to a variety of flavours of canned cat food were
      more likely to be diagnosed with hyperthyroidism than were those fed only one
      flavour (OR=3.8; 95% CI=1.5-9.6). The presence of dental disorders was associated
      with a 5.5-fold increase in the risk of being diagnosed as hyperthyroid and this
      association was independent of the cat's age (95% CI=1.7-17.5). CONCLUSIONS: The
      results of this study support and extend those in several earlier reports and
      show that cats in New Zealand are, in many respects, similar to cats in Europe
      and North America in terms of their susceptibility to hyperthyroidism. The
      finding that female cats are predisposed to hyperthyroidism is at variance with
      most previously published work. It remains unclear which, if any, of the
      identified disease associations are causal, so further studies of this
      increasingly prevalent feline endocrinopathy are warranted.

PMID- 15731837
TI  - Profiling the New Zealand Thoroughbred racing industry. 2. Conditions interfering
      with training and racing.
AB  - AIM: To describe and enumerate conditions that interrupted training and racing in
      a population of Thoroughbred racehorses in New Zealand. METHODS: A longitudinal
      study design was used to collect data on horses training under the care of 20
      licensed racehorse trainers from venues in the mid to lower regions of the North
      Island between October 1997 and July 2000. Incidence rates were reported for
      first and second occurrences for different categories of musculoskeletal injury
      (MSI), and first occurrences of upper and lower respiratory tract disease, using
      training days as time-at-risk. The proportion of horses that retired or died due
      to MSI, respiratory tract or miscellaneous conditions was used to estimate risk
      of exit for each type of event. Duration of training preparation, starts per 100
      training days, and proportion of starts that ended in first, second or third
      place, were calculated for horses at risk for first MSI, and all subsequent MSIs.
      In training preparations that had at least one start and that ended in MSI, the
      cumulative percentage of MSIs by day of diagnosis was reported for 0-21 days
      after the last start in the preparation. RESULTS: Horses (n=1,571) were followed
      during 3,333 training preparations and 392,290 training days. Events associated
      with the end of a training preparation or spell period included MSI (n=834),
      respiratory event (RE; n=165), miscellaneous event (ME; n=58), and voluntary
      retirements (n=360). Causes of MSI included lameness (n=400), shin soreness
      (n=207), tendon and ligament conditions (n=98), injury or laceration (n=56),
      fractures (n=55), and back disorders (n=18). MSIs involved the limbs in 97% of
      cases, and the lower limbs up to the carpus or hock in the fore- and hindlimbs,
      respectively, in 81% of cases. Most (93%) lower limb conditions involved a
      forelimb while 70% of MSIs that involved structures above the carpus or hock
      involved a hindlimb. Incidence rates (IRs) are reported for each age group for
      first and second occurrences of MSI, and first occurrence of upper and lower
      respiratory tract disease. The risk of MSI was higher in horses that had incurred
      one previous MSI (RR 1.4, 95% CI=1.2-1.7; p<0.001) than in horses without any
      previous MSI. The proportion of horses that exited due to death or retirement
      varied with the type of injury, and the highest proportion was associated with
      recurrent fractures, and tendon and ligament injuries (46.2 and 44.4%,
      respectively). The overall IR of horses exiting the study due to retirement or
      death increased with increasing age, and was higher in females than males for
      horses aged 2, 3, 4, and > or =5 years. A reduction in the number of starts per
      100 training days was observed in horses aged > or =5 years when returning to
      training after an initial MSI (p=0.004). Male horses of all age groups and
      females younger than 4 years had shorter median training preparations (p<0.05)
      when returning to training after an initial MSI compared with preparations at
      risk for a first occurrence of MSI. Between 27 and 62% of cases of MSI that
      occurred in training preparations after at least one start were reported on the
      day of the last start, and the remainder were reported in the days to weeks
      following the last start of that preparation. CONCLUSION: Incidence rates, and
      proportions of affected horses that retired or died as a result of injury or
      disorder varied with type of injury and age of horse. Horses returning to
      training after an initial MSI were at higher risk of subsequent MSIs and showed
      changes in duration of training preparations, but little change in starts per 100
      training days or probability of placing in each start. MSIs in racing horses were
      less likely to be reported on the day of a race than at other times in the
      training preparation for all ages except 2-year-olds.

PMID- 15731838
TI  - Effect of grazing pasture with a low selenium content on the concentrations of
      triiodothyronine and thyroxine in serum, and GSH-Px activity in erythrocytes in
      cows in Chile.
AB  - AIM: To determine the effect of grazing pasture that had a low selenium (Se)
      concentration on serum concentrations of triiodothyronine (T3) and thyroxine
      (T4), and erythrocyte glutathione peroxidase (GSH-Px) activity in dairy cows.
      METHODS: Forty pregnant Friesian cows were grazed on pasture that contained 0.03
      0.04 ppm Se on a dry matter (DM) basis. Two months before parturition, 20 cows
      were randomly selected and treated with 1 mg Se/kg bodyweight subcutaneously, as
      barium selenate (Group Se-S). The other group (Se-D) was not supplemented. Blood
      samples were taken before supplementation (-60 days) and 30, 60, 90, 180 and 270
      days after parturition, for determination of concentrations of T3 and T4 in
      serum, and GSH-Px activity in erythrocytes. RESULTS: Erythrocyte GSH-Px activity
      in the Se-D group was <60 U/g haemoglobin (Hb) throughout the experiment.
      Supplementation increased (p<0.05) activities to >130 U/g Hb throughout
      lactation. Mean serum concentrations of T4 in Se-D and Se-S cows increased from
      23.7 (SEM 0.7) and 23.4 (SEM 0.8) nmol/L, respectively, in the prepartum period
      to 69.6 (SEM 0.1) and 67.6 (SEM 0.2) nmol/L, respectively, at 180 days of
      lactation (p<0.01), and no effect of Se supplementation was evident. Serum
      concentrations of T3 in Se-D cows decreased (p<0.05) from 1.6 (SEM 0.1) nmol/L
      prepartum to 1.0 (SEM 0.2) nmol/L at the beginning of lactation, and remained
      lower (p<0.05) than those in the Se-S cows which did not decrease after calving
      and ranged from 1.9 (SEM 0.1) to 2.4 (SEM 0.2) nmol/L throughout lactation.
      CONCLUSIONS: Serum T3 concentrations decreased during early lactation in
      unsupplemented cows grazing pastures low in Se (0.03-0.04 ppm) and both serum T3
      and erythrocyte GSHPx activities were consistently lower throughout lactation
      compared with Se-supplemented cows. Se supplementation had no effect on serum T4
      concentrations.

PMID- 15731839
TI  - Nasal infection with Scedosporium apiospermum in a dog.
AB  - CASE HISTORY: A 2-year-old female Siberian Husky was presented with a 6-month
      history of sneezing and mucous discharge from the right nostril. CLINICAL
      FINDINGS: Reduced airflow through the right nostril was evident. Radiographs
      showed subtle loss of detail of turbinates within the right nasal chamber.
      Rhinoscopy revealed swollen and erythematous turbinates and a white mass within
      the caudal aspect of the right nasal cavity. Histopathologically, there was a
      heavy mixed inflammatory infiltrate in the submuscosa of the right turbinate, and
      the presence of fungal hyphae and spores in the white mass. A heavy growth of
      Scedosporium apiospermum was cultured from the mass. DIAGNOSIS: Chronic rhinitis
      of the right nasal cavity and infection with S. apiospermum. CLINICAL RELEVANCE:
      This is the first reported case of S. apiospermum isolated from the nasal cavity
      of a dog in New Zealand. Fungal culture is necessary to differentiate this fungus
      from Aspergillus spp.

PMID- 15731840
TI  - Fatal levamisole toxicosis of captive kiwi (Apteryx mantelli).
AB  - CASE HISTORY: Nine of 24 captive kiwi treated with oral levamisole at a dose
      between 25-43 mg/kg showed signs of respiratory distress. Six died within 4 h of
      treatment and the remaining three made a full recovery within 24 h. CLINICAL AND
      PATHOLOGICAL FINDINGS: Within 3-4 h of treatment, the affected birds had an
      elevated respiratory rate, mucoid nasal discharge and rapidly became comatose.
      Post mortem examination revealed accumulation of thick mucus in the oral cavity
      and trachea. There was severe pulmonary congestion and oedema and early
      bronchopneumonia in the lungs of five of the birds. In two birds, there was acute
      hepatic degeneration and necrosis and one bird had acute pancreatic degeneration
      and necrosis. DIAGNOSIS: Acute levamisole toxicity. CLINICAL RELEVANCE: Kiwi were
      acutely sensitive to levamisole toxicity at doses that are well within the safe
      range for domestic poultry. Levamisole should not be used as an anthelmintic in
      kiwi.

PMID- 15731841
TI  - A survey of the prevalence of emerging macrocyclic lactone resistance and of
      benzimidazole resistance in sheep nematodes in the lower North Island of New
      Zealand.
AB  - AIM: To investigate the occurrence of emerging macrocyclic lactone (ML)
      resistance and of resistance to benzimidazole anthelmintics on a number of sheep
      farms in the North Island of New Zealand. METHODS: On commercial sheep farms
      (n=30) in the Taihape district in the North Island of New Zealand, 30 animals
      were randomly allocated to one of two equal-sized groups and treated with either
      half of the recommended dose rate of ivermectin (half of 0.2 mg/kg), or with the
      full recommended dose rate of oxfendazole (4.5 mg/kg). The ivermectin treatment
      only was used on a further six properties. Faecal egg counts, accompanied by
      pooled larval cultures, were conducted on all samples at the time of treatment
      and 7-10 days later. RESULTS: Resistance, as indicated by a <95% faecal egg count
      reduction (FECR) in both instances, was found to oxfendazole on 13/30 (43%) farms
      and to a half dose of ivermectin on 12/36 (33%) properties. For oxfendazole, such
      resistance was found to involve all six nematode genera whereas for ivermectin it
      was almost entirely restricted to Ostertagia and Cooperia infections.
      CONCLUSIONS: These results indicate that emerging ML resistance may be more
      common on sheep farms in New Zealand than is generally realised. They also
      suggest that the half-dose ivermectin faecal egg count reduction test (FECRT) may
      offer some very practical benefits for parasite control by providing early
      warning of developing resistance to ML drenches and by signalling the possible
      imminent failure of these at their therapeutic dose rates. The sensitivity and
      reliability of this procedure may be further enhanced by the inclusion of larval
      cultures.

PMID- 15731842
TI  - Heat stress as a manageable risk factor to mitigate pneumonia in lambs.

PMID- 15731852
TI  - Asymmetric organocatalysis.
AB  - The field of asymmetric organocatalysis is rapidly developing and attracts an
      increasing number of research groups around the world. Here we present a brief
      overview of this area, guided by a mechanistic classification. Accordingly,
      organocatalysts are categorized as either Lewis base, Lewis acid, Bronsted base,
      or Bronsted acid catalysts.

PMID- 15731853
TI  - The selective aerobic oxidation of methylaromatics to benzaldehydes using a
      unique combination of two heterogeneous catalysts.
AB  - A unique combination of a supported cobalt complex and the first example of
      supported NHPI in acetic acid gives a surprisingly stable heterogeneous catalytic
      system for the selective aerobic oxidation of methylaromatics to benzaldehydes at
      atmospheric pressure.

PMID- 15731854
TI  - Cyclization of samarium diiodide-generated vinyl radicals in 6-(pi-exo)-exo-dig
      mode.
AB  - Radical cyclization of vinyl iodides in 6-(pi-exo)-exo-dig mode were effected by
      SmI2 to give exo-cyclic dienes fused to six-membered rings.

PMID- 15731855
TI  - Tandem one pot asymmetric conjugate addition-vinyl triflate formation-cross
      coupling methodology.
AB  - Optically active vinyl triflates are obtained and employed in a series of one pot
      metal-catalyzed tandem asymmetric transformations.

PMID- 15731856
TI  - Synthesis of the beta-hydroxydopa-gamma-hydroxy-delta-sulfinylnorvaline component
      of ustiloxins A and B.
AB  - The dopa-sulfinylnorvaline component of ustiloxins A and B has been prepared
      using an Evans salen-Al-catalysed aldol reaction with a 6-mercaptoisovanillin
      derivative, followed by incorporation of the norvaline group and asymmetric
      oxidation of the resulting sulfide to give the corresponding sulfoxide.

PMID- 15731857
TI  - A highly stereoselective ether directed palladium catalysed aza-Claisen
      rearrangement.
AB  - A highly stereoselective rearrangement of allylic trichloroacetimidates to
      allylic trichloroamides has been achieved using adjacent ether groups to direct
      facial coordination of the palladium(II) catalyst.

PMID- 15731858
TI  - Theoretical study of the o-OH participation in catechol ester ammonolysis.
AB  - The possible catalytic effect of the vicinal hydroxyl group during the
      ammonolysis of acetylcatechol has been studied by first principle calculations. A
      very efficient intramolecular catalysis was found to occur when the catechol
      ester o-OH group is deprotonated: the activation energy of the ammonolysis
      decreases by 24 kcal mol(-1) as compared to that of acetylphenol ammonolysis.
      Using this value, the o-oxyanion-catalysed intramolecular ammonolysis was
      estimated to be orders of magnitude faster than the ammonolysis of acetylphenol
      or nonionised acetylcatechol. The analogy with the aminolysis of peptidyl-tRNA
      that occurs during protein biosynthesis implies several orders of magnitude
      acceleration due to complete or partial deprotonation of its 3'-terminal
      adenosine 2'-OH providing a mechanistic possibility for general acid-base
      catalysis by the ribosome.

PMID- 15731859
TI  - Conformational studies of free and Li+ complexed jasplakinolide, a cyclic
      depsipeptide from the Fijian marine sponge Jaspis splendens.
AB  - The complexation of Li+ to jasplakinolide, a marine sponge derived cyclic
      depsipeptide showed preferential binding to two out of four carbonyl oxygens (C
      10, C-14) and the electrons of the aromatic system of the beta-tyrosine amino
      acid residue. This is in contrast to previous results obtained by others who
      proposed complexation to three out of four available carbonyl oxygens (C-1, C-10,
      C-14). The structure of the complex in CD3CN was determined by NOE restrained
      molecular dynamic calculations. Structures of the uncomplexed jasplakinolide were
      calculated in CDCl3 and CD3CN for comparison.

PMID- 15731860
TI  - TBADH activity in water-miscible organic solvents: correlations between enzyme
      performance, enantioselectivity and protein structure through spectroscopic
      studies.
AB  - The enantioselective reduction of 2-pentanone to (R)- and (S)-2-pentanol by
      Thermoanaerobacter (formerly Thermoanaerobium) brockii alcohol dehydrogenase
      (TBADH) in mixtures of water and water-miscible organic solvents was
      investigated. Significant enzymatic activity was retained in up to 87% methanol,
      ethanol and acetonitrile. The changes in enzyme activity as a function of organic
      solvent were correlated to structural alterations of TBADH with a series of
      spectroscopic studies (fluorescence, fluorescence quenching and circular
      dichroism (CD)). Interestingly, this study shows that the tetrameric form of
      TBADH is not critical for catalytic performance.

PMID- 15731861
TI  - Unexpected Z-stereoselectivity in the Ramberg-Backlund reaction of diarylsulfones
      leading to cis-stilbenes: the effect of aryl substituents and application in the
      synthesis of the integrastatin nucleus.
AB  - With certain substituent patterns, benzyl benzyl sulfone systems have been found
      to give unexpectedly high Z-stereoselectivity (up to E:Z = 1:16) in the Meyers
      variant of the Ramberg-Backlund reaction. A range of sulfones, bearing various
      aryl substituents, were explored to rationalize this unprecedented selectivity
      for Z-stilbene systems. This high level of double bond stereocontrol has also
      been utilized in the synthesis of integrastatin nucleus, the core of two highly
      bioactive anti-HIV compounds.

PMID- 15731862
TI  - Design and synthesis of inositolphosphoglycan putative insulin mediators.
AB  - The binding modes of a series of molecules, containing the glucosamine (1-->6)
      myo-inositol structural motif, into the ATP binding site of the catalytic subunit
      of cAMP-dependent protein kinase (PKA) have been analysed using molecular
      docking. These calculations predict that the presence of a phosphate group at the
      non-reducing end in pseudodisaccharide and pseudotrisaccharide structures
      properly orientate the molecule into the binding site and that
      pseudotrisaccharide structures present the best shape complementarity. Therefore,
      pseudodisaccharides and pseudotrisaccharides have been synthesised from common
      intermediates using effective synthetic strategies. On the basis of this
      synthetic chemistry, the feasibility of constructing small pseudotrisaccharide
      libraries on solid-phase using the same intermediates has been explored. The
      results from the biological evaluation of these molecules provide additional
      support to an insulin-mediated signalling system which involves the intermediacy
      of inositolphosphoglycans as putative insulin mediators.

PMID- 15731863
TI  - Simple, versatile and highly diastereoselective synthesis of 1,3,4-trisubstituted
      2-oxopiperazine-containing peptidomimetic precursors.
AB  - The selective O-deprotection of (1'S)-4-(tert-butoxycarbonyl)-1-[1'
      phenylmethyloxymethyl-2'-[(tert-butyldimethylsilyl)oxy]ethyl]-2-oxopiperazine
      furnished an enantiomerically pure alcohol whose regio- and diastereoselective C3
      alkylation yielded either (3R)- or (3S)-1,3,4-trisubstituted-2-oxopiperazines in
      high diastereomeric purity. These derivatives were efficiently transformed into
      (1'R)- or (1'S)-peptide templates utilizable to prepare peptidomimetics. This
      method provides easy access to each 1,3,4-trisubstituted-2-oxopiperazine
      diastereomer and facilitates, through the large choice of substituents at the 3
      position together with the chemistry that can be performed on the N1 substituent,
      the preparation of a large number of diastereomerically pure constrained
      peptidomimetics from a single precursor.

PMID- 15731864
TI  - Cu(II) acetate- and Mn(III) acetate-mediated radical reactions of [60]fullerene
      with ketonic compounds.
AB  - The copper(II) acetate monohydrate- or manganese(III) acetate dihydrate-mediated
      reaction of [60]fullerene with beta-keto esters 1a-1c or with beta-diketones
      1d,1e in the presence of 4-dimethylaminopyridine afforded only dihydrofuran-fused
      C60 derivatives 2a-2e. However, aromatic methyl ketones 3a-3c gave two kinds of
      products: methanofullerenes 4a-4c and dihydrofuran-fused C60 derivatives 5a,5b.
      Possible reaction mechanisms are proposed.

PMID- 15731865
TI  - Enantioselective synthesis of erythro-4-deoxyglycals as scaffolds for target- and
      diversity-oriented synthesis: new insights into glycal reactivity.
AB  - An efficient, enantioselective synthesis of erythro-4-deoxyglycals has been
      developed using asymmetric aldehyde allylation and tungsten-catalyzed alkynol
      endo-cycloisomerization as the key steps. These versatile synthetic scaffolds
      have been elaborated to a variety of products using stereoselective
      transformations that are complementary to those available using the corresponding
      threo glycals. This work has provided valuable insights into the relationships
      between glycal structure and reactivity. In addition, a new diene-forming side
      reaction during tungsten-catalyzed alkynol cycloisomerization has been
      discovered.

PMID- 15731866
TI  - Catalytic asymmetric addition of beta-keto phosphonates to an activated imine-
      formation of optically active functionalized phosphonate alpha-amino acid
      derivatives.
AB  - The direct stereoselective addition of an activated imine to beta-keto
      phosphonates in the presence of chiral Lewis acid complexes is developed. The
      evaluation of different activated imines shows that an N-tosyl-alpha-imino ester
      adds in a diastereo- and enantioselective fashion to beta-keto phosphonates
      activated by especially chiral copper(II)-bisoxazoline complexes. An evaluation
      of Lewis acids, chiral ligands and reaction conditions, such as solvent, bases
      and other additives, shows that high yields, moderate diastereoselectivity and
      good enantioselectivity are obtained. The scope of the reaction is demonstrated
      for the reaction of beta-keto phosphonates and finally, the mechanism for the
      catalytic stereoselective step is presented.

PMID- 15731868
TI  - Radical substitution with azide: TMSN3-PhI(OAc)2 as a substitute of IN3.
AB  - TMSN3 and PhI(OAc)2 were found to promote high-yield azide substitution of
      ethers, aldehydes and benzal acetals. The reaction is fast and occurs at zero to
      ambient temperature in acetonitrile. However, it is essential for the reaction
      that TMSN3 is added subsequent to the mixture of PhI(OAc)2 and the substrate. A
      primary deuterium kinetic isotope effect was found for the azidonation of benzyl
      ethers both with TMSN3-PhI(OAc)2 and with IN3. Also a Hammett free energy
      relationship study of this reaction showed good correlation with sigma+ constants
      giving with rho-values of -0.47 for TMSN3-PhI(OAc)2 and -0.39 for IN3. On this
      basis a radical mechanism of the reaction was proposed.

PMID- 15731867
TI  - Applications of the amino-Cope rearrangement: synthesis of tetrahydropyran, delta
      lactone and piperidine targets.
AB  - We report a novel approach to some chiral tetrahydropyran and delta-lactone
      targets that utilizes the asymmetric amino-Cope rearrangement as a key synthetic
      step. Products of amino-Cope rearrangement chemistry have also been applied to
      access piperidine targets, further demonstrating the potential of the
      methodology.

PMID- 15731869
TI  - Model studies toward the synthesis of kirkine.
AB  - In model studies towards the synthesis of kirkine, the carbon skeleton was
      constructed using a radical cascade reaction. Two different approaches towards
      the synthesis have been examined as well as the regioselectivity of the radical
      cyclisation.

PMID- 15731870
TI  - Studies towards the enantioselective synthesis of 5,6,8-trisubstituted amphibian
      indolizidine alkaloids via enaminone intermediates.
AB  - Investigations aimed at the enantioselective total synthesis of indolizidine
      223A, a recently described 5,6,8-trisubstituted indolizidine alkaloid from a
      dendrobatid frog, are described. tert-Butyl (2R,3R)-3-amino-2-ethylhexanoate and
      its (2S,3R)-diastereomer, prepared in several steps from lithium N-benzyl-N-[(1R)
      1-phenylethyl]amide and tert-butyl (2E)-hex-2-enoate by the Davies protocol,
      served as chiral building blocks from which two complementary suites of
      diastereomeric intermediates were made en route to pivotal tert-butyl 3-[2
      (alkoxycarbonylmethylene)pyrrolidin-1-yl]-2-ethylhexanoate intermediates 20 and
      21. Cyclisation of these enaminones, achieved by acid hydrolysis of the tert
      butyl esters and activation of the liberated carboxylic acids as mixed
      anhydrides, afforded 6-ethyl-7-oxo-5-propyl-1,2,3,5,6,7-hexahydroindolizine-8
      carboxylate esters 28 and 29. Several further transformations of these potential
      scaffolds for the synthesis of the target alkaloidal systems are also reported.

PMID- 15731871
TI  - Design and synthesis of novel sugar-oxasteroid-quinone hybrids.
AB  - A new class of sugar-oxasteroid-quinone hybrid molecules has been designed and
      synthesized involving an efficient enyne metathesis/Diels-Alder reaction
      strategy.

PMID- 15731872
TI  - Chemical models for aspects of the photosynthetic reaction centre: synthesis and
      photophysical properties of tris- and tetrakis-porphyrins that resemble the
      arrangement of chromophores in the natural system.
AB  - Tris-porphyrin and tetrakis-porphyrin arrays 1 and 2 are proposed as models for
      the arrangement of the chromophores that constitute photosynthetic reaction
      centres (PRC's). Their porphyrinic chromophores are similar in distance apart to
      the key chromophores of PRC's and the C2 symmetric arrangement of the macrocycles
      that constitute the 'special pair' where charge separation occurs is also
      incorporated. The use of zinc(II) and gold(III) chelation establishes an energy
      gradient for photoinduced electron transfer across each compound. Synthesis was
      achieved in good yields through a strategy that used the construction of
      biquinoxalinyl and Troger's base linkages between the porphyrinoid components.
      Compounds which are bis-porphyrin molecular components of the arrays were also
      synthesised. Photophysical analyses indicate that long-range photoinduced energy
      and electron transfer processes occur in the extended arrays in addition to those
      occurring in the component bis-porphyrins. Evidence for step-wise electron
      transfer between terminal zinc(II)-chelated and gold(III)-chelated porphyrins has
      been detected in both porphyrins 1 and 2 in polar solvents, representing charge
      transfer across 35 A and 50 A, respectively. At 298 K, in deaerated benzonitrile,
      the lifetime of the charge transfer state of the tris-porphyrin 1 is 150 ns and
      the lifetime of the charge transfer state of tetrakis-porphyrin 2 is 59.4 micros;
      very long when compared to simpler chemical model systems, but still much shorter
      than the 1 s lifetime of the charge separated state of natural PRC's in cell
      membranes.

PMID- 15731873
TI  - Synthesis of phosphorofluoridates and phosphorofluoridothioates via the
      phosphoramidite approach.
AB  - We present a very efficient synthetic procedure leading to the
      phosphorofluoridates RO-P(O)(OH)F 1 or phosphorofluoridothioates RO-P(S)(OH)F 2,
      which is based on the intermediary of fluorophosphoramidites (RO)P(F)N(i)Pr2 5 [R
      = 9-(hydroxyethyloxymethyl)guaninyl), 3'azido-3'deoxythymidinyl, thymidinyl,
      anhydrothymidinyl, cholesteryl, N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'
      deoxyadenosinyl]. The activation of the amino group was performed with
      trimethylchlorosilane (TMCS).

PMID- 15731875
TI  - Mechanisms of photoinduced electron transfer reactions of lappaconitine with
      aromatic amino acids. Time-resolved CIDNP study.
AB  - CIDNP techniques were applied to the investigation of the elementary mechanism of
      photoinduced interaction between anti-arrhythmic drug lappaconitine and amino
      acids tyrosine and tryptophan. It has been shown that the reactions involve the
      formation of lappaconitine radical anion. Lappaconitine radical anion is unstable
      and rapidly eliminates N-acetyl anthranilic acid via protonation and ether bond
      cleavage. The rate constant of ether bond cleavage was estimated to be equal to 4
      x 10(5) s(-1). The role of single electron transfer is discussed in the light of
      the model of drug-receptor interactions.

PMID- 15731874
TI  - Thermotropic liquid-crystalline peptide derivatives: oligo(glutamic acid)s
      forming hydrogen-bonded columns.
AB  - We report on new thermotropic liquid-crystalline oligo(amino acid) derivatives
      forming columnar structures. These are based on branched oligo(glutamic acid)s
      and 2-(3,4-dialkyloxyphenyl)ethyl moieties. An oligo(glutamic acid) derivative,
      alpha,gamma-bis(L-glutamoyl) L-glutamic acid tetra[2-(3,4
      dioctadecyloxyphenyl)ethyl]ester, shows a hexagonal columnar phase, whilst a
      glutamic acid derivative, alpha,gamma-bis[2-(3,4-dioctadecyloxyphenyl)ethyl] L
      glutamate, does not show a mesophase. Hydrogen bonds formed by the oligo(glutamic
      acid) moieties should contribute to the induction of the columnar liquid
      crystalline properties. In addition, we have examined the effects of the
      molecular chirality of the oligo(glutamic acid) parts and the functionalisation
      at the focal position of the taper shaped molecules on the liquid-crystalline
      properties of the compounds.

PMID- 15731876
TI  - Structure-activity relationships of galabioside derivatives as inhibitors of E.
      coli and S. suis adhesins: nanomolar inhibitors of S. suis adhesins.
AB  - Four collections of Gal alpha1-4Gal derivatives were synthesised and evaluated as
      inhibitors of the PapG class II adhesin of uropathogenic Escherichia coli and of
      the P(N) and P(O) adhesins of Streptococcus suis strains. Galabiosides carrying
      aromatic structures at C1, methoxyphenyl O-galabiosides in particular, were
      identified as potent inhibitors of the PapG adhesin. Phenylurea derivatisation at
      C3' and methoxymethylation at O2' of galabiose provided inhibitors of the S. suis
      strains type P(N) adhesin with remarkably high affinities (30 and 50 nM,
      respectively). In addition, quantitative structure-activity relationship models
      for E. coli PapG adhesin and S. suis adhesin type P(O) were developed using
      multivariate data analysis. The inhibitory lead structures constitute an
      advancement towards high-affinity inhibitors as potential anti-adhesion
      therapeutic agents targeting bacterial infections.

PMID- 15731877
TI  - Neutral cumulene oxide CCCCO is accessible by one-electron oxidation of [CCCCO]-*
      in the gas phase.
AB  - Calculations at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-31G* level of theory indicate
      that doublet [CCCCO]-* is a stable species which should undergo collision-induced
      Franck-Condon vertical oxidation under neutralisation-reionisation conditions (
      NR+) to produce both triplet CCCCO (ground state) and singlet CCCCO. Some of the
      neutral CCCCO species formed (particularly the triplet) should be stable for the
      microsecond duration of the NR experiment, whereas others will be energised
      (particularly the singlet) and should decompose to C3 and CO. The [CCCCO]-*
      radical anion has been formed in the ion source of the mass spectrometer by the
      reaction CH3OCH2C[triple bond]C-CO-CH(CH3)2 + O-* --> [CCCCO]-* + CH3O* + H2O +
      (CH3)2CH*. The -NR+ spectrum of [CCCCO]-* shows a recovery signal at m/z 64
      corresponding to ionised CCCCO, together with a pronounced peak at m/z 36 (CCC+*)
      produced by ionisation of CCC (formed by the reaction CCCCO --> CCC + CO). The
      experimental observations are in agreement with the predictions of the
      theoretical study.

PMID- 15731878
TI  - 3-Aryl beta-carbolin-1-ones as a new class of potent inhibitors of tumor cell
      proliferation: synthesis and biological evaluation.
AB  - A novel three-step synthesis of 3-aryl beta-carbolin-1-ones from non-indole
      starting materials has been developed. The two nitrogen atoms in beta-carbolin-1
      one were introduced efficiently by Michael addition of ethyl
      acetamidocyanoacetate to chalcone. The desired pyridone and indole rings were
      assembled by an intramolecular ketone-nitrile annulation mediated by aqueous HCl
      HOAc and a Cu(I)-catalyzed intramolecular N-arylation of the amide, respectively.
      The target compounds were found to possess significant activity against tumor
      cell proliferation.

PMID- 15731879
TI  - Involvement of proton transfer in the reductive repair of DNA guanyl radicals by
      aniline derivatives.
AB  - The most easily oxidized sites in DNA are the guanine bases, and major
      intermediates produced by the direct effect of ionizing radiation (ionization of
      the DNA itself) are electron deficient guanine species. By means of a radiation
      chemical method (gamma-irradiation of aqueous thiocyanate), we are able to
      produce these guanyl radicals in dilute aqueous solutions of plasmid DNA where
      the direct effect would otherwise be negligible. Stable modified guanine products
      are formed from these radicals. They can be detected in the plasmid conversion to
      strand breaks after a post-irradiation incubation with a DNA base excision
      endonuclease enzyme. If aniline compounds are also present, the yield of modified
      guanines is strongly attenuated. The mechanism responsible for this effect is
      electron donation from the aniline compound to the guanyl radical, and it is
      possible to derive rate constants for this reaction. Aniline compounds bearing
      electron withdrawing groups (e.g., 4-CF3) were found to be less reactive than
      those bearing electron donating groups (e.g., 4-CH3). At physiological pH values,
      the reduction of a guanyl radical involves the transfer of a proton as well as of
      an electron. The mild dependence of the rate constant on the driving force
      suggests that the electron is not transferred before the proton. Although the
      source of the proton is unclear, our observations emphasize the importance of an
      accompanying proton transfer in the reductive repair of oxidative damage to
      guanine bases which are located in a biologically active double stranded plasmid
      DNA substrate.

PMID- 15731880
TI  - Generation of alpha-phosphonovinyl radicals and development of a new route to
      highly functionalized vinylphosphonates and vinylphosphonate-incorporated
      carbocyclic or heterocyclic compounds via a radical trapping sequence.
AB  - The first direct generation of synthetically useful alpha-phosphonovinyl radicals
      was achieved by treatment of alpha-phosphonovinyl halides with a tributyltin
      radical. The alpha-phosphonovinyl radicals 2a-d were trapped with electron-rich
      olefins and an electron-deficient olefin to produce alpha-functionalized
      vinylphosphonates 3a-f in 16-55% yields. The alpha-phosphonovinyl radicals 7e-g
      containing the YCH2CH=CH2 (Y = O, CH2, S) substituent at the beta-position
      afforded mixtures of 5-exo and 6-endo cyclization products, 5e-g and 6e-g, in
      good yields. The 5-exo/6-endo product ratios increase in the following order of
      the beta-substituent: OCH2CH=CH2 > CH2CH2CH=CH2 > SCH2CH=CH2. The effects of the
      beta-substituents upon the cyclization reaction were discussed. Radical
      cyclization of alpha-phosphonovinyl radicals bearing functional groups such as
      geranyloxy, geranylthio, and (2-cyclohexen-1-yl)thio groups at the beta-position
      afforded 5-exo, 5-exo and 6-endo, and cis-fused-5,6-ring cyclization products
      incorporating an alpha,beta-unsaturated phosphonate unit within the ring,
      respectively, in good yields. The alpha-phosphonovinyl radical 20 underwent
      tandem radical cyclization-radical cyclization to produce a mixture of two
      isomeric bicyclo[4.3.0]nonenes including a vinylphosphonate moiety in high yield.

PMID- 15731881
TI  - A versatile synthesis of pyrazolo[3,4-c]isoquinoline derivatives by reaction of 4
      aryl-5-aminopyrazoles with aryl/heteroaryl aldehydes: the effect of the
      heterocycle on the reaction pathways.
AB  - The reaction of 4-(3,4-dimethoxyphenyl)-5-aminopyrazoles 7A-D with aromatic and
      heterocyclic aldehydes in strong acidic media (trifluoroacetic or formic acid)
      has been studied. The initial azomethine derivatives 8 undergo cyclization
      similar to the Pictet-Spengler condensation to form the intermediate 4,5
      dihydroisoquinolines 9 which readily dehydrogenate giving 5-aryl(heteroaryl)
      pyrazolo[3,4-c]isoquinoline derivatives 10 as the final products. Whereas for
      benzaldehyde and its derivatives this one-pot synthesis presents a convenient
      general route to 5-aryl-pyrazolo[3,4-c]isoquinolines 10, in the case of
      heterocyclic aldehydes the product structure varies markedly with the structure
      of the aldehyde used: (i) 3-pyridyl-, 3-quinolyl-, 3-thienyl-, and 1,2,3
      thiadiazolyl-5-carboxaldehydes give 5-heteroarylpyrazolo[3,4-c]isoquinolines;
      (ii) 1-methylbenzimidazolyl-2-carboxaldehyde gives only intermediate azomethine
      8Dh, which does not cyclize; (iii) 1-R-3-indolylcarboxaldehydes (R = H, CH3,
      CH2Ph) eliminate the heteroaryl fragment resulting in 5-unsubstituted
      pyrazolo[3,4-c]isoquinolines 11. Thienyl-2-carboxaldehyde reacts by both pathways
      (i) and (iii) depending on the reaction conditions. The single crystal X-ray
      structures for 10Dj, 10Cd and 11D provide confirmation of the different types of
      products formed in these reactions. Mechanisms which explain these
      transformations are presented.

PMID- 15731882
TI  - Noncovalent inhibition of the serine proteases, alpha-chymotrypsin and trypsin by
      trifluoro(organo)borates.
AB  - A series of potassium organotrifluoroborates were synthesized. Their stability to
      hydrolysis was determined in D2O, TRIS and phosphate buffer. It was found that in
      both D2O and TRIS buffers, these compounds are quite stable, whereas in phosphate
      buffer rapid hydrolysis occurs. Based on these results, a study was undertaken to
      determine whether potassium organotrifluoroborates can serve as protease
      inhibitors. It was found that potassium organotrifluoroborates increased
      inhibition by at least an order of magnitude over the corresponding boronates.
      Dixon plots showed that these compounds are reversible competitive inhibitors of
      alpha-chymotrypsin and trypsin. Based on 19F NMR, we speculate that they
      inactivate the enzymes as a result of the formation of hydrogen-bonds between
      fluorine atoms of the inhibitors and the serine protease.

PMID- 15731883
TI  - Long-chain acyl-CoA hydrolase in the brain.
AB  - Long-chain acyl-CoA hydrolases are a group of enzymes that cleave acyl-CoAs into
      fatty acids and coenzyme A (CoA-SH). Because acyl-CoAs participate in numerous
      reactions encompassing lipid synthesis, energy metabolism and regulation,
      modulating intracellular levels of acyl-CoAs would affect cellular functions.
      Therefore, acyl-CoA synthetases have been intensively studied. In contrast, acyl
      CoA hydrolases have been less investigated, especially in the brain despite the
      fact that its long-chain acyl-CoA hydrolyzing activity is much higher than that
      in any other organ in the body. However, recent studies have dissected the
      multiplicity of this class of enzymes on a genomic basis, and have allowed us to
      discuss their function. Here, we describe a cytosolic long-chain acyl-CoA
      hydrolase (referred to as BACH) that is constitutively expressed in the brain,
      comparing it with other acyl-CoA hydrolases found in peripheral organs that have
      a role in fatty acid oxidation.

PMID- 15731884
TI  - Production of amino acids by Azotobacter vinelandii and Azotobacter chroococcum
      with phenolic compounds as sole carbon source under diazotrophic and
      adiazotrophic conditions.
AB  - Azotobacter vinelandii strain ATCC 12837 and Azotobacter chroococcum strain H23
      (CECT4435) were tested to grow in N-free or NH(4)Cl amended chemically defined
      media, with protocatechuic acid or sodium p-hydroxybenzoate as sole carbon (C)
      sources at a concentration of 2 mmol/L. Both substrates supported grow at similar
      rates than bacteria grown in control media amended with 2 mmol/L sodium succinate
      as C source. The two strains produced aspartic acid, serine, glutamic acid,
      glycine, hystidine, threonine, arginine, alanine, proline, cysteine, tyrosine,
      valine, methionine, lysine, isoleucine, leucine and phenylalanine after 72 h of
      growth in chemically defined media with 2 mmol/L of phenolic compounds or sodium
      succinate as sole C source amended or unamended with 0.1% (w/v) NH(4)Cl.
      Qualitative and quantitative production of all amino acids was not affected by
      the use of different C and N substrates.

PMID- 15731885
TI  - The vacuum cleft sign: an uncommon radiological sign.
AB  - The intravertebral vacuum cleft sign (VCS) is an uncommon radiological sign,
      characterized by a radiolucent zone in the vertebral body. It is composed of 95%
      nitrogen and small amounts of oxygen and carbon dioxide. Post-traumatic ischemic
      necrosis could be its physiopathological mechanism, along with other pathologies
      like osteoporosis, corticosteroid therapy, diabetes, arteriosclerosis,
      alcoholism, multiple myeloma, bone metastasis and osteomyelitis. The broad
      diagnosis is made by antero-posterior X-ray, but computed tomography scan (CT
      scan) and magnetic resonance imaging (MRI) may help with the differential
      diagnosis. The aims of this paper are, on one hand, to communicate the clinical
      case of a 73-year-old osteoporotic woman with traumatic vertebral fractures who
      developed this sign in her radiological survey. On the other hand, its secondary
      aims are to review the medical literature about this sign and to show the
      clinical and radiological evolution after a percutaneous vertebroplasty.

PMID- 15731886
TI  - An experimental study of spider-related covariation bias in 8- to 13-year-old
      children.
AB  - Covariation bias can be defined as phobic subjects' tendency to overestimate the
      association between phobic stimuli and aversive outcomes. The current study
      presents two experiments that examined this type of cognitive bias in children
      aged 8-13 years (N=147 in Experiment 1, N=240 in Experiment 2). Children
      completed a self-report questionnaire for measuring spider fear and then
      participated in a card game in which fear-relevant (i.e., spider) and fear
      irrelevant (i.e., weapon and Pokemon) pictures were equally paired with negative
      and positive outcomes (respectively losing and winning candy). No evidence was
      found for a relationship between children's level of spider fear and the tendency
      to link negative consequences to fear-relevant pictures. Various methodological
      and theoretical explanations for this null finding are discussed.

PMID- 15731887
TI  - Maternal negative affect and perceptions of "problem children" in the family.
AB  - This study investigates whether depressive tendencies or anger/hostility is
      associated with an increased propensity for a mother to target a particular child
      in the family as the "problem child." The 180 participants were drawn from a
      larger cohort of urban, low-income mothers and young children. Maternal data were
      gathered from measures of self-reported and observed maternal emotionality.
      Sibling unfavored status was assessed by maternal verbal comparison of siblings.
      Results were consistent in showing that neither maternal depressive nor hostile
      affect is, by itself, predictive of a tendency to single out one child as a
      "troublemaker." The significance of these results for causal models about
      differential parental treatment is discussed.

PMID- 15731889
TI  - Maternal emotions and self-efficacy beliefs in relation to boys and girls with
      AD/HD.
AB  - This study examined the impact of child gender on mothers' emotional responses to
      AD/HD, self-efficacy beliefs and perceived severity of AD/HD. Mothers (N = 118)
      of pre-schoolers were presented with a vignette describing a typical boy or girl
      with AD/HD and then completed three scales relating to their emotional response
      to AD/HD behaviour, their sense of parenting efficacy and their attributions
      about the severity of problems described. AD/HD behaviour elicited negative
      emotions and maternal self-efficacy was low, especially for male AD/HD. Perceived
      severity of the behaviour was negatively correlated with maternal sense of self
      efficacy. These findings suggest that mothers of "normal" children have fixed
      negative emotions and low sense of self-efficacy towards a child with AD/HD and
      that these factors are key elements for change in the implementation of a
      therapeutic programme.

PMID- 15731888
TI  - Prediction of behavioral problems in Chilean schoolchildren.
AB  - Five hundred and thirty five Chilean schoolchildren were evaluated with a test
      retest procedure using teacher and parent questionnaires in first and sixth
      grade, respectively, and a measure of self-esteem in sixth grade. According to
      teachers' ratings, disobedience/aggression, shyness and hyperactivity persisted.
      Cross-predictions were found: disobedience/aggression increased the risk of
      cognitive/concentration problems, which predicted emotional immaturity, while
      hyperactivity predicted disobedience/aggression. Teacher's global opinion of poor
      achievement predicted cognitive/concentration problems, and poor conduct
      predicted hyperactivity. Behavioral problems rated by parents in first grade
      predicted their persistence. Detection of problems in first grade predicts sixth
      grade outcomes, providing information for implementing preventive interventions.

PMID- 15731890
TI  - The lay concept of childhood mental disorder.
AB  - The structure of lay people's concepts of childhood mental disorder was
      investigated in a questionnaire study and examined for convergence with the
      Diagnostic and Statistical Manual (DSM-IV). Eighty-four undergraduates who had no
      formal education in abnormal psychology rated 54 conditions--36 DSM-IV childhood
      disorders and 18 non-disorders--on features proposed in technical definitions of
      mental disorder. The lay concept of childhood mental disorder was narrower than
      the DSM-IV, although most conditions were perceived to warrant professional help.
      Three dimensions described beliefs about childhood psychopathology: social
      deviancy, harmful dysfunction, and harmful environment. Harmful dysfunction was
      related to mental disorder and help seeking judgments.

PMID- 15731891
TI  - Children with functional motor limitations: the effects on family strengths.
AB  - Sixty children with functional motor limitations (age range from 15 months to 7
      years 3 months) and their parents participated in the study. The objective was to
      explore the relationship of the severity of their restrictions on family
      strengths. Functional motor abilities of the children were assessed using Autti
      Ramo's Scale. Cognitive functions were assessed using the Swedish standardized
      version of the Griffiths Scales of Mental Development. Family strengths were
      indexed using the Family Functioning Style Scale. The social-economical status,
      children's age and caretakers' age were taken into account. Overall, the results
      indicated that family strengths were rather strong. Only families rearing a child
      with severe participation limitations (functional motor limitations and cognitive
      difficulties) showed less strengths concerning family identity and internal
      coping relative to families with a child with milder participation limitations.

PMID- 15731892
TI  - Feedback and education improve physician compliance in use of lung-protective
      mechanical ventilation.
AB  - OBJECTIVE: Use of lung-protective mechanical ventilation (MV) by applying lower
      tidal volumes is recommended in patients suffering from acute lung injury (ALI)
      or acute respiratory distress syndrome (ARDS). Recent data suggest that lung
      protective MV may benefit non-ALI/ARDS patients as well. This study analyzed
      tidal volume settings in three ICUs in The Netherlands to determine the effect of
      feedback and education concerning use of lung-protective MV. DESIGN AND SETTING:
      Observational study in one academic and two nonacademic "closed format" ICUs.
      PATIENTS: Intubated mechanically ventilated subjects. INTERVENTIONS: Feedback and
      education concerning lung-protective MV with special attention to the importance
      of closely adjusting tidal volumes to predicted body weight (PBW). RESULTS: Tidal
      volumes declined significantly within 6 months after intervention (from 9.8+/-2.0
      at baseline to 8.1+/-1.7 ml/kg PBW) as the percentage of undesirable ventilation
      data points, defined as tidal volumes greater than 8 ml/kg PBW (84% vs. 48%).
      There were no differences between patients meeting the international definition
      criteria for ALI/ARDS and those not. Only four patients received tidal volumes
      less than 6 ml/kg PBW. Lower tidal volumes were still used after 12 months. Tidal
      volumes in patients on mandatory MV and patients breathing on spontaneous modes
      were similar. CONCLUSIONS: Feedback and education improve physician compliance in
      use of lung-protective MV.

PMID- 15731893
TI  - Teaching difficult airway management: is virtual reality real enough?

PMID- 15731894
TI  - Identification and functional characterisation of genes and corresponding enzymes
      involved in carnitine metabolism of Proteus sp.
AB  - Enzymes involved in carnitine metabolism of Proteus sp. are encoded by the cai
      genes organised as the caiTABCDEF operon. The complete operon could be sequenced
      from the genomic DNA of Proteus sp. Amino acid sequence similarities and/or
      enzymatic analysis confirmed the function assigned to each protein involved in
      carnitine metabolism. CaiT was suggested to be an integral membrane protein
      responsible for the transport of betaines. The caiA gene product was shown to be
      a crotonobetainyl-CoA reductase catalysing the irreversible reduction of
      crotonobetainyl-CoA to gamma-butyrobetainyl-CoA. CaiB and CaiD were identified to
      be the two components of the crotonobetaine hydrating system, already described.
      CaiB and caiD were cloned and expressed in Escherichia coli. After purification
      of both proteins, their individual enzymatic functions were solved. CaiB acts as
      betainyl-CoA transferase specific for carnitine, crotonobetaine, gamma
      butyrobetaine and its CoA derivatives. Transferase reaction proceeds, following a
      sequential bisubstrate mechanism. CaiD was identified to be a crotonobetainyl-CoA
      hydratase belonging to the crotononase superfamily. Because of amino acid
      sequence similarities, CaiC was suggested to be a betainyl-CoA ligase. Taken
      together, these results show that the metabolism of carnitine and crotonobetaine
      in Proteus sp. proceeds at the CoA level.

PMID- 15731896
TI  - Transition to drug addiction: a negative reinforcement model based on an
      allostatic decrease in reward function.
AB  - RATIONALE: The transition from initial drug use to drug addiction has been
      proposed to result from an allostatic decrease in reward function driven by an
      overactivation of brain antireward processes. OBJECTIVES: How decreased reward
      function explains compulsive drug use is not entirely clear at present, and is
      still a subject for debate. METHODS: We present a quantitative model of cocaine
      self-administration that integrates pharmacokinetic, pharmacodynamic, and
      motivational factors to address this question. The model assumes that reward
      system responsivity is a homeostatically regulated process where the desired
      level of responsivity (called the reward set point) is initially different from
      the baseline level. The reduction or correction of this difference or error in
      reward function would drive cocaine self-administration. RESULTS: Theoretical
      data obtained by computer simulation fit the experimental data obtained in
      animals self-administering cocaine (i.e., the within-session pattern of self
      injections, the shape and curvature of the dose-injection function, the nonlinear
      relationship between drug intake and regulated drug effects). Importantly,
      simulation of an allostatic decrease in reward system responsivity exacerbates
      the initial error that drives self-administration, thereby increasing both the
      intake of, and the motivation for, the drug. This allostatic change manifests as
      a vertical shift in the dose-injection function similar to that seen in animals
      with escalating cocaine self-administration. CONCLUSIONS: The present model
      provides a satisfactory explanation of escalated drug intake and suggests a novel
      negative reinforcement view of addiction based on an allostatic decrease in
      reward function.

PMID- 15731898
TI  - Direct ureteric length measurement from intravenous pyelography: does height
      represent ureteric length?
AB  - Ureteric length is the most important factor for determining the ideal length of
      a ureteric stent. In most of the literature, ureteric length is estimated
      according to a patient's height. We investigated the reliability of a patient's
      height as a measure of ureteric length. We measured the actual length of the
      ureteric trace (ALUT) and the linear distance (LD) from the ureterorenal junction
      to the ureterovesical junction by intravenous pyelography (IVP), using a 15 min
      view. A total of 203 patients (100 men, 103 women, 406 ureters) with normal
      findings were studied, and ALUT, LD and height were measured. The mean patient
      height was 164.3 +/- 8.3(SD) cm. Mean ALUTs of the right and left ureters were
      23.4 +/- 1.9 cm and 24.4 +/- 2.0 cm, respectively, and the mean LDs of the right
      and left ureters were 22.1 +/- 1.9 cm and 22.9 +/- 2.0 cm, respectively. Height
      was significantly correlated with the ALUTs of both sides, but these were not
      linear (r2 = 0.024 right, 0.059 left). However, LD showed significant linear
      correlations with the ALUTs of both sides (r2 = 0.879 right, 0.884 left). Two
      formulas to estimate the ALUT from LD were suggested: right ALUT = 0.94 x right
      LD + 2.6, left ALUT = 0.96 x left LD + 2.4. Our results demonstrated that patient
      height does not provide a reliable estimate of ureteric length. LD by IVP is
      preferable to patient height when estimating the ureteric length.

PMID- 15731899
TI  - Diagnostic value and cost utility analysis for urine Gram stain and urine
      microscopic examination as screening tests for urinary tract infection.
AB  - The aim of this study was to evaluate the diagnostic properties of urine Gram
      stain and urine microscopic examination for screening for urinary tract infection
      (UTI), and to perform an additional cost utility analysis. This descriptive study
      was performed on 95 urine samples sent for urine culture to the Department of
      Microbiology, Faculty of Medicine, Chulalongkorn University. The first part of
      the study was to determine the diagnostic properties of two screening tests
      (urine Gram stain and urine microscopic examination). Urine culture was set as
      the gold standard and the results from both methods were compared to this. The
      second part of this study was to perform a cost utility analysis. The sensitivity
      of urine Gram stain was 96.2%, the specificity 93.0%, the positive predictive
      value 94.3% and the negative predictive value 95.2%. False positives occurred
      with a frequency of 7.0% and false negatives 3.8%. For the microscopic
      examination, the sensitivity was 65.4%, specificity 74.4%, positive predictive
      value 75.6% and negative predictive value 64.0%. False positives occurred with a
      frequency of 25.6% and false negatives 34.6%. Combining urine Gram stain and
      urine microscopic examination, the sensitivity was 98.1%, specificity 74.4%,
      positive predictive value 82.3% and negative predictive value 97.0%. False
      positives occurred with a frequency of 25.6% and false negatives 1.9%. However,
      the cost per utility of the combined method was higher than either urine
      microscopic examination or urine Gram stain alone. Urine Gram stain provided the
      lowest cost per utility. Economically, urine Gram stain is the proper screening
      tool for presumptive diagnosis of UTI.

PMID- 15731897
TI  - Preliminary array analysis reveals novel genes regulated by ovarian steroids in
      the monkey raphe region.
AB  - We hypothesize that ovarian hormones may improve serotonin neuron survival. We
      sought the effect of estradiol (E) and progesterone (P) on novel gene expression
      in the macaque dorsal raphe region with Affymetrix array analysis. Nine spayed
      rhesus macaques were treated with either placebo, E or E+P via Silastic implant
      for 1 month prior to euthanasia (n=3 per treatment). RNA was extracted from a
      small block of midbrain containing the dorsal raphe and examined on an Agilent
      Bioanalyzer. The RNA from each monkey was labeled and hybridized to an Affymetrix
      HG_U95AV Human GeneChip Array. After filtering and sorting, 25 named genes
      remained that were regulated by E, and 24 named genes remained that were
      regulated by supplemental P. These genes further sorted into functional
      categories that would promote neuronal plasticity, transmitter synthesis, and
      trafficking, as well as reduce apoptosis. The relative abundance of four pivotal
      genes was examined in all nine animals with quantitative RT-PCR and normalized by
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH). E+/-P caused a significant
      threefold reduction in JNK-1 (a pro-apoptosis gene, p<0.007); and a significant
      sixfold decrease in kynurenine mono-oxygenase (produces neurotoxic quinolones,
      p<0.05). GABA-A receptor (alpha3 subunit; benzodiazepine site) and E2F1
      (interferes with cytokine signaling) were unaffected by E, but increased
      sevenfold (p<0.02) and fourfold (p<0.009), respectively, upon treatment with P.
      In summary, subsets of genes related to tissue remodeling or apoptosis were up-
      or down-regulated by E and P in a tissue block containing the dorsal raphe. These
      changes could promote cellular resilience in the region where serotonin neurons
      originate.

PMID- 15731900
TI  - Optimization of erythritol and glycerol accumulation in conidia of Beauveria
      bassiana by solid-state fermentation, using response surface methodology.
AB  - Entomopathogenic fungi are widely produced for use as mycoinsecticides.
      Therefore, improvement of the shelf life of fungal propagules under good and
      adverse conditions should be a pre-requisite of their production. In order to
      improve conidial physiology as well as mycoinsecticide efficiency, culture
      conditions may be varied. The Doehlert design was used to generate response
      surfaces with an estimation of the parameters of the quadratic model allowing the
      study of three different factors at a different number of levels. This
      experimental design was applied to optimize water activity (aw), pH, and
      fermentation time for Beauveria bassiana conidial production and accumulation of
      polyols in solid-state fermentation. Thus, it was possible to identify the region
      in the experimental range in which the optimum values of these parameters were
      simultaneously achieved. Maximal conidia production was achieved at pH 5-6 and
      aw=0.999. Under these conditions, polyol accumulation was 3 mg erythritol/g
      conidia and 29.6 mg glycerol/g conidia. However, maximal polyol accumulation was
      achieved at pH 4.5 and aw 0.950; erythritol production increased 33-fold and
      glycerol production 4.5-fold. Under these conditions conidia production was 1,000
      times lower. The possibilities of increasing the quality of the biocontrol agent
      without neglecting yield are discussed.

PMID- 15731895
TI  - Ionotropic and metabotropic glutamate receptor structure and pharmacology.
AB  - RATIONALE: L: -Glutamate is the major excitatory neurotransmitter in the central
      nervous system (CNS) and mediates its actions via activation of both ionotropic
      and metabotropic receptor families. The development of selective ligands,
      including competitive agonists and antagonists and positive and negative
      allosteric modulators, has enabled investigation of the functional roles of
      glutamate receptor family members. OBJECTIVE: In this review we describe the
      subunit structure and composition of the ionotropic and metabotropic glutamate
      receptors and discuss their pharmacology, particularly with respect to selective
      tools useful for investigation of their function in the CNS. RESULTS: A large
      number of ligands are now available that are selective either for glutamate
      receptor subfamilies or for particular receptor subtypes. Such ligands have
      enabled considerable advances in the elucidation of the physiological and
      pathophysiological roles of receptor family members. Furthermore, efficacy in
      animal models of neurological and psychiatric disorders has supported the
      progression of several glutamatergic ligands into clinical studies. These include
      ionotropic glutamate receptor antagonists, which have entered clinical trials for
      disorders including epilepsy and ischaemic stroke, alpha-amino-3-hydroxy-5-methyl
      4-isoazolepropionic acid (AMPA) receptor positive allosteric modulators which are
      under evaluation as cognitive enhancers, and metabotropic glutamate receptor 2
      (mGluR2) agonists which are undergoing clinical evaluation as anxiolytics.
      Furthermore, preclinical studies have illustrated therapeutic potential for
      ligands selective for other receptor subtypes in various disorders. These include
      mGluR1 antagonists in pain, mGluR5 antagonists in anxiety, pain and drug abuse
      and mGluR5 positive allosteric modulators in schizophrenia. CONCLUSIONS:
      Selective pharmacological tools have enabled the study of glutamate receptors.
      However, pharmacological coverage of the family is incomplete and considerable
      scope remains for the development of novel ligands, particularly those with in
      vivo utility, and for the their use together with existing tools for the further
      investigation of the roles of receptor family members in CNS function and as
      potentially novel therapeutics.

PMID- 15731901
TI  - Identification of a homogentisate-1,2-dioxygenase gene in the fungus Exophiala
      lecanii-corni: analysis and implications.
AB  - Exophiala lecanii-corni is a dimorphic fungus capable of degrading several
      volatile organic compounds (VOCs) including ethylbenzene, which has been
      classified as a hazardous air pollutant by the Environmental Protection Agency.
      In contrast to bacterial species, little is known about the mechanisms of fungal
      degradation of VOCs. The results described herein suggest a potential pathway for
      ethylbenzene degradation in E. lecanii-corni via styrene, phenylacetate and
      homogentisate. Consistent with this proposed pathway, a full-length homogentisate
      1,2-dioxygenase gene (ElHDO) has been identified, cloned and sequenced. The
      nucleotide sequence of ElHDO consists of a 1,452-bp open reading frame encoding a
      protein with 484 amino acids. The expression of the gene product increases when
      grown on ethylbenzene, further suggesting that it could be involved in
      ethylbenzene degradation and may be responsible for the aromatic ring cleavage
      reaction. In addition, a 907-bp fragment isolated upstream from this gene shares
      78% sequence identity at the amino acid level with the amino acid sequences of
      two fungal phenylacetate hydroxylase genes. This observation suggests that the
      genes responsible for ethylbenzene degradation may be clustered. This research
      constitutes the first step towards a better understanding of ethylbenzene
      degradation in E. lecanii-corni.

PMID- 15731902
TI  - ["Pneumocytoma" or "sclerosing hemangioma": histogenetic aspects of a rare tumor
      of the lung].
AB  - Aspects of histogenesis and nomenclature of so called "sclerosing hemangioma" of
      the lung (WHO 1999) are discussed and compared with immunohistochemical findings
      in eight examined operation specimen. The lesion is characterised by the presence
      of typical surface cells, which can be related to type II pneumocytes.
      Progesterone-receptor positive stromal cells may derive from primitive
      mesenchymal cells. Endothelial proveniance of tumor cells could not be confirmed
      by immunohistochemistry. Therefore, this rare usually benign pulmonary neoplasm
      should be entitled "pneumocytoma" analogous to the suggestion of several other
      authors.

PMID- 15731903
TI  - Effects of the acute exposure to the electromagnetic field of mobile phones on
      human auditory brainstem responses.
AB  - The purpose of this study was to evaluate the short-term effects of the
      electromagnetic fields (EMF) of mobile phones on human auditory brainstem
      responses. This prospective study of healthy adults evaluated the influence of
      EMF. Eighteen healthy adult volunteers participated in this study. Mobile
      telephones emitting signals in the region of 900 MHz and with the highest SAR
      value of 0.82 W/kg were positioned in direct contact to the right ear, which was
      exposed to the phone signal for 15 min before and after ABR testing with click
      stimuli of 60 and 80 dB nHL intensities. The latencies of the waves and interwave
      latencies were measured on screen by an experienced audiologist. The differences
      of the mean latencies of waves I, III and IV were not significant in initial and
      post-exposure ABR measurements at both 60 and 80 dB nHL stimulus levels ( P
      >0.05). Similarly, differences of the mean interwave intervals I-III, I-V and III
      V remained insignificant at the initial and postexposure ABR measurements at
      stimulus levels of both 60 and 80 dB nHL ( P >0.05). Acute exposure to the EMF of
      mobile phones does not cause perturbations in ABR latencies. However, these
      negative results should not encourage excessive mobile communication, because
      minor biological and neurophysiological influences may not be detectable by the
      current technology.

PMID- 15731904
TI  - Antiphospholipid antibodies in patients with sensorineural hearing loss.
AB  - Sensorineural hearing loss can be associated with autoimmune diseases and the
      presence of antiphospholipid antibodies. Sixty patients (mean age 47 years, range
      18-76 years) with sudden sensorineural hearing loss were studied with audiograms,
      stapedial thresholds, otoacoustic emissions, positional and caloric testing. The
      serologic testing included antibodies against phosphatidylserine and beta(2)
      glycoprotein. Additionally, a group of 34 patients (mean age 65 years, range 31
      81 years) with normal tension glaucoma was examined because in a previous study
      these patients were reported to have elevated concentrations of antiphospholipid
      antibodies with a coincidence of progressive sensorineural hearing loss. The
      baseline for antiphospholipid antibody levels was established in a control group
      of 40 healthy blood donors. In 12 of the 60 patients with sudden sensorineural
      hearing loss, levels of antiphospholipid antibodies were elevated.
      Antiphosphatidylserine IgM antibodies were significantly lower compared to
      controls and patients with the combination of hearing loss and normal tension
      glaucoma (Fisher's exact two-sided test, P < 0.01). Our data suggest that
      antibodies against beta2-glycoprotein seem to coincidence with an acute event,
      such as sudden sensorineural hearing loss, whereas antibodies against
      phosphatidylserine IgG are detectable in the prolonged sequel, such as in
      patients with progressive sensorineural hearing loss and normal tension glaucoma.

PMID- 15731905
TI  - Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age:
      analysis of 96 patients.
AB  - We analysed data of 96 infants (under 1 year of age) with haemophagocytic
      lymphohistiocytosis (HLH) from the registry of an HLH study conducted during 1986
      2002 in Japan. The cases were classified into five groups. The diagnosis of
      familial HLH (FHL) as group 1 (n = 27) was made with positive family history
      and/or recent molecular test for perforin and Munc13-4 mutations. Neonatal
      enterovirus- or herpes simplex virus-associated HLH as group 2a (n = 7), Epstein
      Barr virus-associated HLH (n = 12) as group 2b, adenovirus- or cytomegalovirus
      associated HLH as group 3 (n = 9) were mostly diagnosed by viral isolation or by
      the detection of viral genome. Juvenile rheumatoid arthritis-associated
      macrophage activation syndrome was classified as group 4 (n = 4) and the
      remaining without known triggers as group 5 (n = 37). The peak onset age was 1-2
      months for group 1, 1-2 weeks for group 2a, 12 months for group 2b, none for
      group 3, 9 months for group 4 and 2 months for group 5. Future novel diagnostic
      measures are required to define the precise nature of HLH in group 5. CONCLUSION:
      These data may provide useful information for neonatologists/ paediatricians in
      the differential diagnosis of haemophagocytic lymphohistiocytosis in early
      infancy.

PMID- 15731906
TI  - Acceptance and timeliness of standard vaccination in children with chronic
      neurological deficits in north-western Switzerland.
AB  - There are no special recommendations for basic vaccinations in patients with
      chronic neurological deficits distinct from the nationwide advocated schedule in
      Switzerland. Reports describing adverse neurological events possibly related to
      vaccinations have attracted public attention. It is unclear if patients with
      chronic neurological deficits are more reluctantly vaccinated compared to healthy
      children. We therefore investigated the acceptance of vaccinations in such
      patients and healthy controls in a retrospective case-control study. At the
      University Children's Hospital, Basel, Switzerland we investigated 100 patients
      with chronic neurological deficits and 200 age-matched healthy controls regarding
      the issue of vaccination rates and ages. The total number of administered
      vaccinations against diphtheria, tetanus, pertussis, polio, Haemophilus
      influenzae type b (Hib), mumps, measles, rubella and hepatitis B were
      significantly lower in patients compared to healthy controls ( P < 0.01 for each
      of the respective vaccines). Patients had an increased risk to receive the third
      pertussis, diphtheria, and tetanus vaccinations (relative risks (RR) for late
      vaccination 1.53, 1.53, and 1.54 respectively, P < 0.01 for all comparisons), the
      second (RR = 1.60, P < 0.05) and third Hib vaccinations (RR = 1.52, P < 0.05),
      and the third polio vaccination (RR = 1.43, P < 0.05) later than controls.
      CONCLUSION: Children with chronic neurological deficits received fewer
      vaccinations than healthy controls. In addition, patients received vaccinations
      later than healthy children. Hence, it may be assumed that children with chronic
      neurological deficits are at an increased risk to acquire preventable infections.
      Therefore, vaccination should be promoted as part of the consultation during a
      routine appointment with the specialist.

PMID- 15731907
TI  - Prevention and management of meconium aspiration syndrome--assessment of evidence
      based practice.

PMID- 15731908
TI  - The effect of the 5-chloro-2-methylthio-6-(1-naphtyloxy)-1H-benzimidazole on the
      tegument of immature Fasciola hepatica in their natural host.
AB  - The damage to the tegument of 3-week-old Fasciola hepatica was evaluated by
      scanning electron microscopy (SEM) following treatment with the 5-chloro-2
      methylthio-6-(1-naphtyloxy)-1H-benzimidazole (called compound alpha) in its
      natural host. For the present study, flukes were raised in pelibuey sheep
      infected orally with metacercariae of F. hepatica; the parasites were recovered
      from the liver of the sacrificed sheep after 6, 12 and 24 h of treatment with
      compound alpha. At 6 h of treatment, the flukes showed some lesions on the
      ventral surface of the anterior region, such as a swollen tegument and blebs. At
      12 h after treatment, the specimens showed structural disorganization and spine
      loss in the ventral anterior region. The tegument of the flukes treated for 24 h
      was completely lost in some areas of the ventral surface, leaving an exposed
      basal lamina. The tegument of immature F. hepatica might be a target organ for
      compound alpha to exert its fasciolicide effect.

PMID- 15731910
TI  - Evaluation of small hypothalamic hamartomas with 3D constructive interference in
      steady state (CISS) sequence.
AB  - Hypothalamic hamartomas are relatively rare, non-neoplastic congenital
      malformations. With conventional MR images alone, small hypothalamic hamartomas
      may be difficult to diagnose because of artifacts from cerebrospinal fluid. We
      present the usefulness of three-dimensional constructive interference in steady
      state sequence for evaluating small hypothalamic hamartomas in three pediatric
      patients.

PMID- 15731911
TI  - A catalytic multi-pumping flow system for the chemiluminometric determination of
      metformin.
AB  - A multi-pumping flow system for the chemiluminometric determination of the
      hypoglycaemic drug metformin was implemented. The developed methodology was based
      on the metformin-induced inhibition (metformin acts as a Cu(II) scavenger) of the
      catalytic effect of Cu(II) ions on the chemiluminescent reaction between luminol
      and hydrogen peroxide. The flow manifold configuration was based on the
      utilisation of multiple solenoid-actuated micro-pumps that were simultaneously
      accountable for sample/reagent introduction and reaction zone
      formation/propulsion, thus resulting in a fully automated, simple and highly
      selective multi-pumping flow system. A versatile sample manipulation allowed the
      establishment of distinct sampling strategies with low reagent consumption. The
      characteristic pulsed flow ensured an effective sample/reagent mixing leading to
      a better and faster reaction zone homogenisation and thus improved analytical
      signals. Linear calibration plots were obtained for metformin hydrochloride
      concentrations ranging from 5 to 15 mg L(-1) with a relative standard deviation
      lower than 2.0% (n=5). Detection limit was 0.94 mg L(-1), and the sampling rate
      was about 95 determinations per hour. The developed methodology was applied to
      the analysis of pharmaceutical formulations and the obtained results were in
      agreement with those furnished by the reference method with relative percentage
      deviations of lower than 1.5%.

PMID- 15731912
TI  - Bioluminescence resonance energy transfer from aequorin to a fluorophore: an
      artificial jellyfish for applications in multianalyte detection.
AB  - In nature, the green light emission observed in the jellyfish Aequorea victoria
      is a result of a non-radiative energy transfer from the excited-state aequorin to
      the green fluorescent protein. In this work, we have modified the photoprotein
      aequorin by attaching selected fluorophores at a unique site on the protein. This
      will allow for in vitro transfer of bioluminescent energy from aequorin to the
      fluorophore thus creating an "artificial jellyfish". The fluorophores are
      selected such that the excitation spectrum of the fluorophore overlaps with the
      emission spectrum of aequorin. By modifying aequorin with different fluorophores,
      bioluminescent labels with different emission maxima are produced, which will
      allow for the simultaneous detection of multiple analytes. By examining the X-ray
      crystal structure of the protein, four different sites for introduction of the
      unique cysteine residue were evaluated. Two fluorophores with differing emission
      maxima were attached individually to the mutants through the sulfhydryl group of
      the cysteine molecule. Two of the fluorophore-labeled mutants showed a peak
      corresponding to fluorophore emission thus indicating resonance energy transfer
      from aequorin to the fluorophore.

PMID- 15731909
TI  - Peutz-Jeghers LKB1 mutants fail to activate GSK-3beta, preventing it from
      inhibiting Wnt signaling.
AB  - Peutz-Jeghers syndrome (PJS) is caused by germline mutations in the LKB1 gene,
      which encodes a serine-threonine kinase that regulates cell proliferation and
      polarity. This autosomal dominant disorder is characterized by mucocutaneous
      melanin pigmentation, multiple gastrointestinal hamartomatous polyposis and an
      increased risk of developing various neoplasms. To understand the molecular
      pathogenesis of PJS phenotypes, we used microarrays to analyze gene expression
      profiles in proliferating HeLa cells transduced with lentiviral vectors
      expressing wild type or mutant LKB1 proteins. We show that gene expression is
      differentially affected by mutations that impair the kinase activity (K78I) or
      alter the cellular localization of the LKB1 protein. However, both mutations
      abrogate the ability of LKB1 to up-regulate the transcription of several genes
      involved in Wnt signaling, including DKK3, WNT5B and FZD2. In addition-and in
      contrast to the wild type protein-these LKB1 mutants fail to activate the GSK
      3beta kinase, which otherwise phosphorylates beta-catenin. The increase in beta
      catenin phosphorylation that occurs upon expression of wild-type LKB1 results in
      transcriptional inhibition of a canonical Wnt reporter gene. This suggests that
      pathogenic LKB1 mutations that lead to activation of the Wnt/beta-catenin pathway
      could contribute to the cancer predisposition of PJS patients.

PMID- 15731913
TI  - Potential application of the reaction between hydroquinone and chromate with
      respect to the kinetic determination of iron.
AB  - The analytical potential of the reaction between hydroquinone and chromate in
      acidic media is explored with respect to the kinetic determination of iron in
      water samples. The extent of the reaction is followed spectrophotometrically at
      350 nm. The reaction occurs more quickly in the presence of the metal ion, but
      the values of absorbance at reaction initiation and completion are not altered.
      No other transitional metal ion affects the course of the reaction, regardless of
      its concentration. This fact represents the most eye-catching and analytically
      exploitable aspect of this indicator reaction. Three procedures used to obtain
      calibration graphs from the same kinetic data are discussed: slope, fixed and
      variable time techniques. The reaction follows a sequence of two consecutive
      steps, both of first-order with respect to the colored species. First-order
      kinetics is preserved in the presence of iron. Curve fitting is used to determine
      the corresponding rate coefficients. The slope method requires much data and uses
      plots of rate constants against analyte concentration for calibration purposes.
      In this case, the best detection limit (0.5 mg l(-1)) is given by the faster
      stage. On the other hand, the rate-determining step enables more precise results.
      The fixed and variable time methods rely on similar principles: they register
      either the value of absorbance achieved at a predetermined reaction time (here,
      50 s) or the time interval required for the absorbance to drop to a predetermined
      value (here, 0.15 absorbance at 350 nm). In both cases, ratios between the
      average value from the blind runs and all individual values are plotted against
      the analyte concentration. The best results (detection limit of 0.3 mg l(-1)) are
      derived from the variable time procedure. Advantageously, neither of the
      techniques require the entire kinetic curve, and so sophisticated equipment is
      not needed.

PMID- 15731914
TI  - Kinetic catalytic determination of trace Cu(II) in water samples with the
      thioglycolic/thiolactic acid-chromate reaction.
AB  - The use of two novel similar indicator reactions as applied to the kinetic
      determination of Cu(II) in water is investigated. The methods rely on the
      catalytic effect of the analyte on the oxidation of thioglycolic (TGA) and
      thiolactic (TLA) acids by chromate in acidic media. The extent of the reactions
      was followed spectrophotometrically at 345 nm. Pseudo-first-order rate
      coefficients, k(obsd), were determined as a function of catalyst concentration.
      Interference of Fe(III) and Pb(II) was suppressed by complexation with
      pyrophosphate. For the reaction of TGA, a linear regression for k(obsd) versus
      [Cu(II)] was obtained for the entire concentration range considered. Although the
      plot corresponding to TLA oxidation exhibits a sharp change of slope at
      approximately 1.8x10(-5) M Cu(II), it can still be described effectively by two
      linear regressions with different slopes. The reaction of TGA is more sensitive
      than that of TLA at low Cu(II) concentration. The opposite is true for higher
      catalyst contents. The detection limits were 65 microg L(-1) for TGA and of 80
      microg L(-1) for TLA oxidation, respectively. The relative standard deviations,
      of 0.4% for TGA and 1.1% for TLA oxidation, respectively, were obtained for five
      replicate runs at 1000 microg L(-1). Samples of river and wastewater from the
      mining region of Baia-Mare, Northern Romania were analyzed using the more
      sensitive reaction of thioglycolic acid. Results were compared to those obtained
      by the officially standardized methods. Good agreement was obtained, even for an
      untreated sample. Measurements did not require prior separation of interfering
      species.

PMID- 15731915
TI  - Ultrasound-assisted extraction and on-line LC-GC-MS for determination of
      polycyclic aromatic hydrocarbons (PAH) in urban dust and diesel particulate
      matter.
AB  - A method has been developed for determination of polycyclic aromatic hydrocarbons
      (PAH) in particulate matter from ambient air and diesel exhaust emissions. It is
      reproducible and accurate and, compared with similar methods for analysis of
      individual PAH components in complex matrices, it is relatively fast and simple.
      Single PAH components can be determined in samples of particulate matter from
      ambient air and diesel exhaust emissions with LOD of approximately 1 pg/sample.
      Further, sample throughput is high, because more than 20 samples can be extracted
      and prepared for analysis in one working (8-h) day. The particulate matter is
      subjected to ultrasound-assisted extraction, a technique that is shown to extract
      PAH from particulate material with efficiencies fully comparable with those of
      Soxhlet extraction. An aliphatic/PAH-enriched fraction is obtained by solid-phase
      extraction before isolation, separation, and identification/quantification of PAH
      by on-line liquid chromatography-gas chromatography-mass spectrometry. The method
      was validated by analysis of US National Institute of Standards and Technology
      (NIST) Standard Reference Materials (SRM) 1649a, Urban Dust, and 2975, Diesel
      Particulate Matter. Results from the method are in good agreement with the NIST
      certified PAH concentrations and with NIST reference PAH concentrations.

PMID- 15731916
TI  - Potential for drug interactions in hospitalized cancer patients.
AB  - OBJECTIVES: To quantify the frequency of potential drug interactions unrelated to
      chemotherapy in cancer patients admitted to our institution, and to define risk
      factors for such interactions. METHODS: Charts of 100 consecutive hospitalized
      cancer patients were reviewed. Patients receiving chemotherapy and/or hormone
      therapy were excluded, as were patients admitted for intensive care. Drug-drug
      interactions were screened with Drug Interaction Facts software, and manually by
      the authors. Potential interactions were graded by levels of severity (severe,
      moderate, minor) and significance (one to five, with one representing the highest
      level of evidence). RESULTS: The median age of the patients was 67 years, and the
      length of hospital stay and the number of drugs per patient were 6 days and eight
      drugs, respectively. In 63 patients 180 potential interactions were detected. Of
      the potential interactions, 18.3% were severe, 56.7% were moderate, and 25% were
      minor. Approximately 7%, 18% and 13% of potential interactions were graded as
      level 1, 2 and 3, respectively. In multivariate analysis, prescriptions with
      eight or more drugs (P=0.0004) and six or more days of hospital stay (P=0.014)
      were independent risk factors for potential interactions. CONCLUSION: Potential
      drug interactions are common among hospitalized cancer patients. Length of
      hospital stay and number of prescribed drugs are risk factors.

PMID- 15731917
TI  - In vitro schedule-dependent interaction between paclitaxel and oxaliplatin in
      human cancer cell lines.
AB  - PURPOSE: In order to define the most effective administration schedule of the
      combination of paclitaxel and oxaliplatin, we investigated the in vitro
      interaction between these drugs in a panel of three human cancer cell lines (AZ
      521 gastric adenocarcinoma cell line, HST-1 tongue squamous carcinoma cell line,
      and KSE-1 esophageal squamous carcinoma cell line). MATERIALS AND METHODS:
      Cytotoxic activity was determined by the WST-1 assay. Different administration
      schedules of the two drugs were compared and evaluated for synergism, additivity,
      or antagonism with a quantitative method based on the median-effect principle of
      Chou and Talalay. Cell cycle perturbation and apoptosis were evaluated by flow
      cytometry. RESULTS: Simultaneous treatment of cells with paclitaxel and
      oxaliplatin showed greater than additive effects. Upon 24-h sequential exposure,
      the sequence of paclitaxel followed by oxaliplatin showed synergistic effects in
      AZ-521 and HST-1 cells, and greater than additive effects in KSE-1 cells, while
      the opposite sequence yielded marked antagonistic effects in all three cell
      lines. Flow cytometric analysis indicated that paclitaxel induced G(2)/M arrest
      with subsequent induction of apoptosis in the sub-G(1) phase. Apoptosis was most
      prominent when paclitaxel preceded oxaliplatin, which produced apoptosis in the
      majority of treated cells (75%). By contrast, the reverse sequence yielded only
      39% induction of apoptotic cells, the rate being not different from those induced
      by each drug singly. CONCLUSIONS: Our findings suggest that the interaction of
      paclitaxel and oxaliplatin is highly schedule-dependent and that the sequential
      administration of paclitaxel followed by oxaliplatin should thus be incorporated
      into the design of a clinical trial.

PMID- 15731919
TI  - Secondary individual prevention of hand dermatitis in geriatric nurses.
AB  - BACKGROUND: The incidence of occupational skin disease (OSD) in geriatric nurses
      (GNs) is increasing in Germany. OBJECTIVES: A prospective controlled study of
      secondary individual prevention (SIP) of OSD in GNs was conducted. METHODS: Two
      hundred and nine participants completed questionnaires prior to the start of the
      program and 3 months after its conclusion. One hundred and two GNs participated
      in an interventional program (intervention group, IG). Severity of OSD was
      classified upon each visit. Delta-TEWL values were measured at regular intervals.
      Findings were compared with those for 107 control group (CG) participants
      consulting a dermatologist on demand. SIP was not offered to CG participants.
      RESULTS: Upon entry, 89% of IG and 90% CG complained of OSD (NS). Dermatologic
      examination revealed skin changes in 90% of IG at first consultation. Upon study
      completion, 59% of IG was free of OSD. Questionnaires 3 months after study
      completion revealed skin lesions in 53% of IG and 82% of CG (p<0.01). Delta-TEWL
      measurements reflected significant improvement of the epidermal barrier during
      SIP in IG (median 6.9-3.0 g/m(2)/h, p<0.001). Three months after study
      completion, 96% of IG and 86% of CG were still employed. CONCLUSIONS: Objective
      dermatologic and skin physiologic data reveal that SIP in GNs is effective in the
      secondary prevention of OSD. Further, IG was superior to CG in terms of health
      maintenance and employment.

PMID- 15731918
TI  - [How much general medical competency does a psychiatrist need?].
AB  - Due to manifold interactions between physical and mental health, there exist
      close interactions between psychiatric care and that from other medical fields.
      In this regard, points of general medical practice are discussed as they relate
      to psychiatric care. The frequency of somatic comorbidities in patients with
      mental disorders and a rising proportion of elderly patients are strong arguments
      for inclusion of general medical elements in psychiatric and psychotherapeutic
      training.

PMID- 15731920
TI  - When a pregnant patient has a suspected pulmonary embolism, what are the typical
      embryo doses from a chest CT and a ventilation/perfusion study?

PMID- 15731921
TI  - High prevalence of Helicobacter pylori infection and monoclonal gammopathy of
      undetermined significance in patients with chronic idiopathic neutropenia.
AB  - The prevalence of Helicobacter pylori infection was evaluated in 120 patients
      with chronic idiopathic neutropenia (CIN), 8 patients with monoclonal gammopathy
      of undetermined significance (MGUS) associated with CIN, and 74 age- and sex
      matched normal volunteers, all derived from the same geographical area. The
      purpose of the study was to investigate the possible causal relationships of H.
      pylori infection with the development of MGUS in CIN patients. We found that the
      prevalence of H. pylori infection was elevated to 69.2% in the group of CIN
      patients, 100% in the group of patients with CIN-associated MGUS, and 32.4% in
      the group of control subjects. No statistically significant difference, however,
      was found in the prevalence of H. pylori infection between CIN patients with
      concomitant MGUS and CIN patients without MGUS, no resolution of the gammopathy
      after eradication of the bacterium, no significant rise in the titers of serum
      anti-H. pylori antibodies, and no formation of an abnormal precipitation line in
      immunoelectrophoresis using a saline extract of NCTC11367 H. pylori reference
      strain as antigen. We concluded that there is no evidence that H. pylori
      infection is the cause of MGUS in CIN patients.

PMID- 15731922
TI  - Seasonal modulation of growth hormone mRNA and protein levels in carp pituitary:
      evidence for two expressed genes.
AB  - Adaptation of eurythermal fish to naturally varying environmental conditions
      involves modulation of expressions of various factors in the hypothalamo
      hypophyseal axis. Here we used three complementary approaches to assess the
      seasonal variation of growth hormone (GH) protein and mRNA levels in pituitary
      glands of acclimatized carp fish. First, a polyclonal antibody raised against an
      oligopeptide derived from the carp GH sequence was used for immunohistochemistry;
      second, oligonucleotides specific for GH transcripts were used for in situ
      hybridization. Specific immunodetection of GH coincides with visualization of GH
      mRNA in the proximal pars distalis, the specific location of somatotroph cells in
      carp pituitary gland. Finally, competitive RT-PCR analyses confirmed that GH
      expression exhibits seasonal cyclical reprogramming with higher levels in summer-
      than in winter-adapted fish. The expression pattern suggests an important role
      for GH in the molecular mechanisms underlying the acclimatization process. In
      parallel, amplification of sequences from the fourth intron and adjacent sites
      from exons IV and V demonstrates the existence of a new GH gene previously
      undescribed. The detection of transcripts corresponding to each gene suggests
      that both GH gene copies are active in the duplicated carp genome and that they
      are similarly affected by seasonal adaptation.

PMID- 15731923
TI  - Hyaluronan synthase expression in pleural malignant mesotheliomas.
AB  - Hyaluronan (HA) is thought to play several important roles in tumor growth,
      tumorigenicity, and tumor dissemination and metastasis. Recently, three isoforms
      of hyaluronan synthase (HAS) have been cloned. Our objective was to determine
      which of the HAS isoforms were expressed in pleural malignant mesotheliomas, the
      most representative lesion of HA-producing tumors. We studied 10 cases of pleural
      malignant mesothelioma using novel antibodies of HAS. We compared HAS expression
      patterns of mesothelioma and pulmonary adenocarcinoma. Immunohistochemically, 9
      of 10 (90%) cases of mesothelioma had extensive reaction to anti-HAS1 and anti
      HAS2 antibodies, while HAS3 overexpression was present in 4 of 10 cases (40%). Of
      20 cases of pulmonary adenocarcinoma, 5 overexpressed HAS1 (25%), 16 of 20 HAS2
      (80%), and 4 of 20 HAS3 (20%). The expression level of HAS1 was significantly
      higher in mesotheliomas than in pulmonary adenocarcinoma (P=0.0036). Our data
      suggests that HAS1 might be a useful positive marker of malignant mesothelioma.
      However, a definitive conclusion should be based on further large-scale studies.

PMID- 15731924
TI  - Establishment and characterization of the permanent human cell line C3842 derived
      from a secondary chondrosarcoma in Ollier's disease.
AB  - The permanent human cell line C3842 was established from a secondary
      chondrosarcoma in a typical case of Ollier's disease. In the present study, we
      analyzed the morphological, cytogenetic and molecular biological characteristics
      of the cultured cells in comparison with the original tumor and investigated the
      invasion properties of the tumor model using functional imaging of proteolysis,
      matrigel assay and chick chorioallantoic membrane assay. C3842 cells exhibit the
      typical features of malignant cartilage tumor cells in vitro, including the
      expression of collagen types II, IX, XI and aggrecan. The proteolytic ability of
      C3842 cells is attributed to the expression of several proteases, such as
      cathepsin B, urokinase plasminogen activator and matrix-metalloproteinase-2,
      which enable the cells to degrade collagen type I and to permeate matrigel
      matrix. In accordance with the biological features in vivo, C3842 cells are not
      able to invade through the epithelium of the chick chorioallantoic membrane. In
      conclusion, the cell line C3842 provides the first model of a secondary
      chondrosarcoma in Ollier's disease in vitro, which is characterized by distinct
      features of such malignant cartilage tumors.

PMID- 15731925
TI  - Leiomyosarcoma and malignant fibrous histiocytoma share similar allelic imbalance
      pattern at 9p.
AB  - Formalin-fixed, paraffin-embedded tissue from 45 soft tissue sarcomas was
      analysed for allelic imbalance/loss of heterozygosity (AI/LOH) of chromosome 9.
      The specimens consisted of 17 cases of soft tissue leiomyosarcoma (LMS), 4 cases
      of cutaneous LMS, 22 cases of conventional malignant fibrous histiocytoma (MFH)
      and 2 cases of angiomatoid fibrous histiocytoma. All cases were categorised
      morphologically and immunohistochemically. DNA was microdissected from normal and
      neoplastic tissues. AI/LOH was performed using six microsatellite markers on the
      9p region. The frequency of allelic imbalance at different loci on chromosome 9p
      was analysed in LMS and MFH and then compared with values previously examined in
      synovial sarcoma and malignant peripheral nerve sheath tumour. Although AI/LOH
      and microsatellite instability (MSI) were more frequent in MFH, LMS and MFH
      groups showed similar patterns of allelic imbalance at the 9p region. Alterations
      of chromosome 9p have been reported in many cell lines and tumours including LMS
      and MFH. 9p21 region encodes p16(INK4A) and p15(INK4B). Allelic imbalance
      observed at 9p 21 in this study suggests that alterations of the negative cell
      cycle regulators may be an important step in the pathogenesis of MFH and LMS.
      However, the most frequent allelic imbalance was observed at 9p24 at D9S230.
      Alterations of this locus were very rare in synovial sarcoma and malignant
      peripheral nerve sheath tumours and were absent in cutaneous LMS and angiomatoid
      fibrous histiocytoma. This locus may point to the existence of a genetically
      altered tumour suppressor gene involved in the pathogenesis of LMS and MFH. Our
      results support the hypothesis that MFHs may represent a morphological pathway in
      tumour progression of LMSs.

PMID- 15731926
TI  - Adenocarcinoma arising in a tailgut cyst with prominent meningothelial
      proliferation and thyroid tissue: case report and review of the literature.
AB  - Tailgut cysts (retrorectal cystic hamartomas) are rare lesions occurring in the
      retrorectal/presacral space of young women, considered to be of developmental
      origin. In this study, we report the clinicopathological characteristics of an
      adenocarcinoma developing in an unusual tailgut cyst. A 47-year-old female
      presented with a 3-month history of an enlarging presacral mass, extending into
      the gluteal area. The patient underwent surgical resection. Microscopic
      examination revealed a mucinous adenocarcinoma with intestinal features arising
      in a tailgut cyst. In addition to the usual components previously described in
      this lesion (cuboidal, columnar, ciliated or squamous epithelial lining with
      scattered smooth muscle fibers in the wall), our case was unique in that it was
      associated with a meningothelial proliferation and benign thyroid tissue with
      oncocytic changes. These additional features bring into question the proposed
      hindgut origin of tailgut cysts.

PMID- 15731927
TI  - A second field metachronous Merkel cell carcinoma of the lip and the palatine
      tonsil confirmed by microarray-based comparative genomic hybridisation.
AB  - Merkel cell carcinoma was diagnosed in a 79-year-old Caucasian woman. The tumour
      was localised to the upper lip and was in stage T2. After successful cryosurgery
      and a 7-year tumour-free period, a new tumour developed in her palatine tonsil.
      Histologically and immunohistochemically, this resembled the tumour in the lip.
      The regional lymph nodes were devoid of metastasis. The paraffin-embedded
      material of the two tumours and the unaffected lymphatic tissue were analysed
      with DNA microarrays for comparative genomic hybridisation to assess the genetic
      relationship of the tumours. In both tumours, regions on 2p and 10p were commonly
      over-represented, while 41 regions on chromosomes 1-4, 6, 8-9, 11 and 14-22 were
      commonly under-represented. Chromosomes 1, 3, 4, 16-18 and X were most frequently
      involved in the DNA losses. In gene copy numbers in the two tumours, 31
      chromosome locations were found to be differently affected. The partly similar
      and partly different molecular patterns indicated a genetic relationship between
      the tumours and excluded the possibility that the tonsillar tumour was a
      metastasis. The findings suggest that a genetically altered field was the reason
      for the development of the tonsillar cancer; thus, it can be regarded
      pathogenetically as a second field tumour.

PMID- 15731928
TI  - [The lymphatic system and the skin. Classification, clinical aspects und
      histology].
AB  - Dermatology offers many clinical examples of abnormalities in the production,
      absorption and transport of lymph. Lymphatic thromboses also occur. Many diseases
      are not named in accordance with their underlying pathogenesis. Malignant
      lymphedema must be recognized immediately. The differential diagnosis of regional
      lymphedema is also part of dermatology. Stemmer sign is a clue to chronic
      lymphedema. Lymphoedema is first divided into primary and secondary forms,
      depending on the cause, and then subdivided into stages depending on severity.
      Complications of chronic lymphedema include recurrent erysipelas, superficial
      lymphangiectases, verrucous lymphedema (papillomatosis lymphostatica) and
      angiosarcoma, which is often multifocal. Established diagnostic approaches are
      available to correctly diagnose lymphatic disease. The treatment of chronic
      lymphedema centers around reducing the edema which then influences all of the
      other problems. The physical therapeutic approach to reducing blockage is the
      best way to achieve these goals.

PMID- 15731929
TI  - Insertion and excision of a transposable element governs the red floral phenotype
      in commercial petunias.
AB  - Commercial cultivars of Petunia hybrida with red flowers (red petunias)
      accumulate cyanidin 3-glucoside as a main floral anthocyanin pigment. The
      conversion of anthocyanidin 3-glucosides to anthocyanidin 3-rutinosides is
      catalyzed by a UDP-rhamnose: anthocyanidin 3-glucoside-rhamnosyltransferase (RT).
      In red petunias, the RT gene is known to be disrupted by the insertion of a
      transposable element (dTph3). We have cloned the dTph3-like element (called dTph3
      C) from a red petunia. Unlike dTph3, dTph3-C harbored a perfect terminal inverted
      repeat. In addition, an excision product (so-called "footprint") of dTph3/dTph3-C
      was found in another red petunia. The RT transcripts harboring this footprint
      could not produce the RT enzyme because a stop codon was created in the footprint
      sequence. The genotypes of the 42 commercial petunias which exhibit different
      anthocyanin pigmentation were determined by multiplex PCR. In this technique, the
      amplified products from normal, dTph3/dTph3-C-inserted, and footprint-retaining
      RT genes can be separated from one another. Our results indicate that the red
      floral phenotype of commercial petunias is governed by insertion and excision
      events of a transposable element in the coding region of the RT gene.

PMID- 15731930
TI  - SNP identification and SNAP marker development for a GmNARK gene controlling
      supernodulation in soybean.
AB  - Supernodulation in soybean (Glycine max L. Merr.) is an important source of
      nitrogen supply to subterranean ecological systems. Single nucleotide-amplified
      polymorphism (SNAP) markers for supernodulation should allow rapid screening of
      the trait in early growth stages, without the need for inoculation and
      phenotyping. The gene GmNARK (Glycine max nodule autoregulation receptor kinase),
      controlling autoregulation of nodulation, was found to have a single nucleotide
      polymorphism (SNP) between the wild-type cultivar Sinpaldalkong 2 and its
      supernodulating mutant, SS2-2. Transversion of A to T at the 959-bp position of
      the GmNARK sequence results in a change of lysine (AAG) to a stop codon (TAG),
      thus terminating its translation in SS2-2. Based on the identified SNP in GmNARK,
      five primer pairs specific to each allele were designed using the WebSnaper
      program to develop a SNAP marker for supernodulation. One A-specific primer pair
      produced a band present in only Sinpaldalkong 2, while two T-specific pairs
      showed a band in only SS2-2. Both complementary PCRs, using each allele-specific
      primer pair were performed to genotype supernodulation against F2 progeny of
      Sinpaldalkong 2 x SS2-2. Among 28 individuals with the normal phenotype, eight
      individuals having only the A-allele-specific band were homozygous and normal,
      while 20 individuals were found to be heterozygous at the SNP having both A and T
      bands. Twelve supernodulating individuals showed only the band specific to the T
      allele. This SNAP marker for supernodulation could easily be analyzed through
      simple PCR and agarose gel electrophoresis. Therefore, use of this SNAP marker
      might be faster, cheaper, and more reproducible than using other genotyping
      methods, such as a cleaved amplified polymorphic sequence marker, which demand of
      restriction enzymes.

PMID- 15731933
TI  - Nonvariceal upper gastrointestinal bleeding.

PMID- 15731931
TI  - [A factorial trial of six interventions for the prevention of postoperative
      nausea and vomiting].
AB  - BACKGROUND: Untreated, one third of patients who undergo surgery will have
      postoperative nausea and vomiting. Although many trials have been conducted, the
      relative benefits of prophylactic antiemetic interventions given alone or in
      combination remain unknown. METHODS: In a randomized, controlled trial of
      factorial design, 5,199 patients at high risk for postoperative nausea and
      vomiting were randomly assigned to 1 of 64 possible combinations of 6
      prophylactic interventions: 1) 4 mg of ondansetron or no ondansetron; 2) 4 mg of
      dexamethasone or no dexamethasone; 3) 1.25 mg of droperidol or no droperidol; 4)
      propofol or a volatile anesthetic; 5) nitrogen or nitrous oxide; 6) remifentanil
      or fentanyl. The primary aim parameter was nausea and vomiting within 24 h after
      surgery, which was evaluated blindly. RESULTS: Ondansetron, dexamethasone, and
      droperidol each reduced the risk of postoperative nausea and vomiting by about
      26%, propofol reduced the risk by 19%, and nitrogen by 12%. The risk reduction
      with both of these agents (i.e., total intravenous anesthesia) was thus similar
      to that observed with each of the antiemetics alone. All the interventions acted
      independently of each other and independently of the patients' baseline risk.
      Consequently, the relative risks associated with the combined interventions could
      be estimated by multiplying the relative risks associated with each intervention.
      However, absolute risk reduction was a critical function of patients' baseline
      risk. CONCLUSIONS: Because antiemetic interventions are similarly effective and
      act independently, the safest or least expensive should be used first.
      Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may
      benefit from a single intervention, and multiple interventions should be reserved
      for high-risk patients.

PMID- 15731932
TI  - A case of Takayasu disease with findings of incomplete Alagille syndrome.
AB  - A 16-year-old girl being followed up for Takayasu arteritis for the last 3 years
      was also found to have Alagille syndrome upon findings of atypical facies,
      posterior embryotoxon, high-pitched voice, osteopenia and hypogonadism. This case
      might imply a possible relationship between Takayasu arteritis and Alagille
      syndrome.

PMID- 15731934
TI  - Therapeutic pancreatic endoscopy.
AB  - Over the past decade, endoscopic retrograde cholangiopancreatography (ERCP) has
      developed from being a diagnostic tool to become one that is primarily used to
      provide therapy. This development occurred first for biliary disorders and more
      recently for primary diseases of the pancreas. Not only can new-generation
      computed tomography (CT), magnetic resonance imaging, and magnetic resonance
      cholangiopancreatography procedures suggest a diagnosis in the majority of
      individuals with pancreatic diseases today; in addition, ERCP-related
      complications can be minimized or avoided altogether in conjunction with positron
      emission tomography or directed cytology or biopsy, either using ultrasound or CT
      guidance, or with tissue obtained during endoscopic ultrasonography. It is
      against this background that papers on therapeutic pancreatic endoscopy published
      during approximately the last year are reviewed here. Despite these developments,
      however, the following three issues concerning current advances in pancreatic
      endotherapy should be emphasized: firstly, most of the techniques reviewed here
      affect only a small number of patients; secondly, most of the techniques have
      been reported only by expert centers; and thirdly, most of the studies concerned
      have lacked control groups, and there is still a paucity of studies investigating
      endoscopic techniques on a randomized basis in comparison with surgery or medical
      therapy for the treatment of most benign and malignant pancreatic disorders.

PMID- 15731935
TI  - Colon polyps and cancer.
AB  - The role of endoscopy, in particular colonoscopy, clearly is paramount in the
      screening, diagnosis, and prevention of colorectal cancer. In preparation for
      writing this "state-of-the-art" review on colon polyps and cancer, a PubMed
      literature search linking the topic with endoscopy yielded an enormous number of
      papers published in peer-reviewed journals just in the past 12 months. I have
      selected a few of these to highlight that I believe are most germane to current
      issues of risk stratification, screening and surveillance, prevention, and the
      premalignant potential of different types of adenomas detected by endoscopy.
      Several of these papers address the advantages and limitations of direct
      colonoscopy screening for colorectal neoplasia, and discuss the emerging role of
      virtual colonoscopy screening.

PMID- 15731936
TI  - Long-term failure of endoscopic suturing in the treatment of gastroesophageal
      reflux: a prospective follow-up study.
AB  - BACKGROUND AND STUDY AIMS: Several endoscopic antireflux therapies have been
      marketed, but long-term data on their objective and clinical efficacy are sparse.
      This report presents prospective 1-year follow-up results, including technical,
      clinical, and functional success rates, for the first of these treatments to be
      developed, endoscopic gastroplication (EGP). PATIENTS AND METHODS: A total of 43
      EGP procedures were carried out in 38 patients with gastroesophageal reflux
      disease (GERD). Two or three EndoCinch gastroplications were constructed at the
      level of the gastric cardia in each patient; five patients were treated twice
      within 6 - 12 months. Each endoscopic suture joined two gastric folds to each
      other as a double fold, known as a "gastroplication", in order to narrow the
      esophagogastric junction. Postprocedure data after 2 months and after 1 year were
      compared with preoperative data, focusing on symptoms, medication requirements,
      endoscopic findings, and pH-metry results. RESULTS: In contrast to the findings
      at 2 months (which showed that 72 % of the sutures were present and that there
      was a reduction in the percentage of time when the esophageal pH was < 4 from
      15.4 % to 8.7 %), the results 1 year after EGP were considered to indicate
      failure of the treatment in all 38 patients because none of them still had all of
      the initially placed gastroplications in situ (90 % of gastroplications were
      lost). The percentage of patients who did not require proton pump inhibitor
      medication decreased from 52 % at 2 months to only 20 % at 1 year and even more
      patients had evidence of reflux esophagitis at 1 year (56 %) than had initially
      demonstrated signs of this (41 %). CONCLUSIONS: EGP has some short-term
      beneficial effects on clinical symptoms and pH-metry. However, mainly due to the
      loss of the endoscopically placed sutures, these effects were not maintained at
      the 1-year follow-up. EGP cannot therefore be recommended for routine clinical
      use. Better endoscopic methods need to be developed, and they should be
      adequately tested before being marketed.

PMID- 15731937
TI  - Are endoscopic antireflux therapies cost-effective compared with laparoscopic
      fundoplication?
AB  - BACKGROUND AND STUDY AIMS: A number of endoscopic antireflux therapies (EATs)
      have emerged as potential nonmedical treatment options for patients with
      gastroesophageal reflux disease (GERD). Concerns about clinical efficacy and
      costs have given rise to debate about their role in GERD management. The costs of
      laparoscopic fundoplication (LF) were compared with the costs of EAT when used in
      a sequential strategy that reserves the option of LF for EAT failure. METHODS: A
      simple mathematical criterion of direct medical costs was applied. Published
      articles concerning EAT were reviewed to assess its effectiveness, durability and
      costs, in order to estimate the parameters of the model. The costs of EAT and LF
      were evaluated from the perspective of a German third-party payer. Only direct
      medical costs were considered. RESULTS: Assuming that EAT has no impact on
      potential LF later on, the outcome of both strategies (LF, or EAT first with LF
      in case of failure of EAT) is identical and preference is a simple question of
      costs. The sequential strategy in nonmedical GERD treatment would be preferable
      if the long-term relief rate with EAT exceeds the ratio of the cost of EAT to the
      cost of LF. Long-term success rates of EAT do not exceed 0.65. At current prices
      EAT is clearly not cost-effective in Germany. CONCLUSION: Our simple criterion
      indicates that EAT would only be cost-effective and beneficial in a sequential
      strategy if the costs of EAT were to be decreased to around 30 % of current
      retail prices. However, long-term studies and randomized controlled trials are
      necessary to finally determine the role of EAT in GERD treatment, and the
      preference may change in either direction.

PMID- 15731938
TI  - Endoscopic ultrasound-guided drainage of pancreatic pseudocysts complicated by
      portal hypertension or by intervening vessels.
AB  - BACKGROUND AND STUDY AIMS: Portal hypertension often coexists with pancreatic
      pseudocysts and is potentially dangerous if a collateral vessel is in the
      vicinity of the needle puncture pathway. Hitherto, there have been no reports of
      pseudocyst drainage in this setting. PATIENTS AND METHODS: Patients who underwent
      endoscopic ultrasound (EUS)-guided pancreatic pseudocyst drainage complicated by
      intervening vessels were assessed for success and outcomes. An Olympus mechanical
      linear-array video echo endoscope GF-UM 140D was used for the drainage procedure
      in all patients. Either a "hot" diathermy technique was employed or a "cold"
      technique using direct aspiration with a 19-G needle, followed by deployment of a
      nasocystic catheter. RESULTS: Eight patients with a symptomatic pseudocyst and
      intervening vessels underwent drainage that was guided (n = 6) or assisted (n =
      2) by EUS. All were found to have successful resolution of the cyst at follow-up
      6 weeks later, while segmental portal hypertension had disappeared in one
      patient. There were no major complications. One patient had transient hemorrhagic
      drainage that resolved by itself. CONCLUSIONS: Pseudocysts complicated by portal
      hypertension or by intervening vessels can be safely drained under EUS guidance,
      even in the absence of color Doppler imaging.

PMID- 15731939
TI  - Relief of reflux symptoms after endoscopic gastroplication may be associated with
      reduced esophageal Acid sensitivity: a pilot study.
AB  - BACKGROUND AND STUDY AIMS: Although the new endoscopic techniques for the
      treatment of gastroesophageal reflux disease (GERD) lead to marked clinical
      benefit, the underlying mechanism of this is unknown. MATERIALS AND METHODS: In
      this prospective study, the effect of endoscopic gastroplication was investigated
      in six patients with GERD, who were assessed before and 4 weeks after treatment.
      The effect on reflux symptoms, quality of life, proton pump inhibitor (PPI)
      consumption, reflux esophagitis, acid exposure, esophageal motility, lower
      esophageal sphincter pressure (LESP), and gastric emptying was measured.
      Esophageal acid sensitivity before and after treatment was investigated using a
      standardized acid provocation test, and compared with that of six age- and sex
      matched healthy controls. RESULTS: Significant clinical benefit and
      discontinuation of PPI consumption after gastroplication was seen. Among the
      objectively measured parameters, only acid exposure was significantly reduced and
      gastric emptying significantly delayed. However, acid exposure remained
      pathologically high. Esophageal acid sensitivity was significantly reduced. The
      induction of heartburn and/or pain was abolished in four patients after
      gastroplication. In two patients the intensity of heartburn/pain was
      significantly reduced by 40 % or 60 %, and the time to provoke heartburn/pain
      significantly prolonged by 40% or 100%. CONCLUSION: These preliminary data
      suggest that the decrease of esophageal sensitivity to acid after endoscopic
      gastroplication is part of the mechanism responsible for the reduction of reflux
      symptoms.

PMID- 15731940
TI  - Feasibility and safety of endoscopic evaluation of gastric emptying.
AB  - BACKGROUND AND STUDY AIMS: Scintigraphy is the currently accepted method for
      evaluation of gastric emptying. Although quantitative, this method is
      complicated, time-consuming, and costly. If a simple endoscopic technique was
      available for those instances when quantification of an emptying abnormality is
      not needed, the same clinical information could be obtained in less time and with
      resource savings. Our aims in this study were therefore to assess the technical
      feasibility, tolerability, and safety of unsedated transnasal esophagogastroscopy
      (T-EG) as a technique for qualitative assessment of gastric emptying. METHODS:
      The study was done in two phases. In the first phase, 18 volunteers (ten men,
      eight women) underwent T-EG at 4 hours, 5 hours, or 6 hours after ingestion of a
      standard meal used for scintigraphic evaluation of gastric emptying without
      radiolabeling. In the second phase, ten volunteers underwent T-EG after
      scintigraphic imaging had demonstrated complete gastric emptying. RESULTS:
      Subjects in both phases tolerated the procedure well and completed the study. In
      the first phase, 13 of 15 volunteers exhibited complete gastric emptying at 6
      hours (87%), while two (13%) revealed some particulate matter in the stomach at
      that time. In the second phase, one of the ten volunteers exhibited a small
      amount of solid food residue in the stomach despite documentation of
      scintigraphic complete emptying. CONCLUSIONS: Evaluation of gastric emptying by
      unsedated T-EG is both feasible and safe. In healthy, asymptomatic individuals,
      complete gastric emptying of solid food may take as long as 6 hours.

PMID- 15731941
TI  - Endoscopic ultrasound imaging of the adrenals.

PMID- 15731942
TI  - Endoscopic appearance of serrated adenomas in the colon.

PMID- 15731943
TI  - Endoscopic detection and diagnosis of 0-IIc neoplastic colorectal lesions.

PMID- 15731944
TI  - Acute esophageal necrosis associated with alcoholic hepatitis: is it black or is
      it white?
AB  - Acute esophageal necrosis is an uncommon condition diagnosed during endoscopy
      from the black appearance of the esophagus. We report three cases of acute
      esophageal necrosis, associated with severe alcoholic hepatitis. The pathogenesis
      was multifactorial in our patients, with gastroesophageal reflux combined with
      hypoperfusion probably being the key factor for the esophageal lesions. The
      patients presented a continuum of endoscopic appearances, ranging from the
      characteristic black esophageal mucosa with ulcerations to a thick white exudate
      that peeled away (pseudomembranes). However, esophageal biopsy specimens from all
      three patients had the same histological pattern of severe inflammation and
      necrosis. Thus, the possibility of acute esophageal necrosis should also be
      considered in patients with extensive necrosis covered by a white exudate, but
      without the characteristic pattern of a "black esophagus"; and the diagnosis
      should subsequently be confirmed by mucosal biopsies. Our report showed that
      ethanol-induced acute esophageal necrosis can appear in patients with a high
      alcohol intake, especially in immunosupressed patients with alcoholic hepatitis.

PMID- 15731945
TI  - Capsule endoscopy, transit times, and Whipple's disease.

PMID- 15731946
TI  - Endoscopic ultrasound-guided drainage of a cystic metastasis in the mediastinum
      that caused tracheal obstruction.

PMID- 15731947
TI  - Early spontaneous slippage of rubber bands with fatal bleeding: a rare
      complication of endoscopic variceal ligation.

PMID- 15731948
TI  - Double pylorus: an unusual endoscopic finding.

PMID- 15731949
TI  - A new device to clarify the position of the endoscope tip during endoscopic
      diagnosis and therapeutic procedures.

PMID- 15731950
TI  - Buried bumper syndrome: endoscopic management using a balloon dilator.

PMID- 15731952
TI  - Esophageal leiomyomatosis diagnosed by endoscopic ultrasound.

PMID- 15731951
TI  - Polypoid Barrett's high-grade dysplasia in a patient with familial adenomatous
      polyposis: a unique association.

PMID- 15731953
TI  - [Pneumology -- epidemiological changes and structural consequences].

PMID- 15731954
TI  - [Bronchial artery embolisation using platinum coils in 52 patients with severe
      pulmonary hemorrhage].
AB  - BACKGROUND: Severe pulmonary hemorrhage ist life-threatening. One of the
      treatment options in case of severe pulmonary hemorrhage is bronchial artery
      embolisation (BAE) with different embolisation materials. PATIENTS AND METHODS:
      Efficacy of BAE using platinum coils was investigated retrospectively in a total
      of 52 patients. 22 suffered from benign lung diseases (angiodysplasia,
      inflammation, bronchiectasia) and 30 patients had lung cancer (lung metastases in
      two cases). RESULTS: Primary hemostasis was achieved in over 90 % of the patients
      (47 of 52). Recurrent BAE was necessary in 23 % of patient with benign etiologies
      and in 50 % of the tumor patients. Comparing the results of the lung cancer
      patients with a control group from a teaching hospital without BAE we found
      survival-advantages for those patients treated with BAE. CONCLUSION: Our results
      underline the usefulness of BAE in severe pulmonary hemorrhage.

PMID- 15731955
TI  - [Chronic cough and pulmonary infiltration].
AB  - HISTORY: A 56-year-old man complain of chronic cough for 6 months without further
      clinical problems. The patient was otherwise in good health and showed only a
      moderate bronchial sound at the left ventral paracordial region. INVESTIGATIONS:
      Thorax X-ray revealed an infiltrate in the lingula with segmental borders. The CT
      scan showed air bronchogramms and bilateral more small infiltrates. DIAGNOSIS,
      TREATMENT, CLINICAL COURSE: Bronchoscopic transbronchial biopsies revealed a BALT
      lymphoma. A seven years old chest X-ray showed the lingual infiltrate in nearly
      the same extension as the current X-ray. Because of the disseminated
      manifestation, the slow course and the good performance status we did not start a
      palliative chemotherapy so far. CONCLUSION: Any pulmonary infiltrate which looks
      like pneumonia must be given a definite diagnosis if there are no clinical signs
      of infection.

PMID- 15731956
TI  - [Pulmonary bleeding after lung transplantation].
AB  - BACKGROUND: Bronchial arteries are not anastomosed during lung transplantation.
      We analyzed the occurrence of pulmonary hemorrhage after transplantation.
      PATIENTS AND METHODS: 235 patients were included. RESULTS: We observed pulmonary
      bleeding in 4/235 patients (1.7 %). All four cases were due to transplant
      specific disorders (arrosion of pulmonary artery in three cases, coagulopathy in
      one patient). CONCLUSIONS: The analysis shows, that usual pulmonary hemorrhage
      does not occur in lung transplant recipients. This underlines the role of
      bronchial arteries in pulmonary hemorrhage of non-LTX-patients.

PMID- 15731957
TI  - [Diagnosis of haemoptoe/haemoptysis].
AB  - Haemoptysis and haemoptoe mainly differ in the amount of expectorated blood.
      Causes of haemoptysis are diverse and include bronchitis, bronchiectasis,
      carcinoma, tuberculosis and other infectious pulmonary disease. Haemoptysis
      almost exclusively involves bronchial arteries, rarely vessels of the pulmonary
      artery circuit. Asphyxia rather than the loss of blood ist life-threatening. 20 -
      30 % of bronchopulmonary bleeding happens without any identifiable cause, about
      90 % of haemoptyses are self-terminating. Chest X-ray is an integral part in each
      evaluation, as is bronchoscopy. Fiberoptic bronchoscopy is easily performed,
      although rigid bronchoscopy considerably extends the armamentarium of diagnostic
      and therapeutic measures. (Pulmangio-) chest CT scan as well as echocardiography
      and angiographic procedures provide extended diagnostic and therapeutic options.
      Surgery may be required in severe bleeding complications or during stable disease
      as a diagnostic approach.

PMID- 15731958
TI  - [Treatment of pulmonary bleeding].

PMID- 15731959
TI  - [Pneumococcal vaccination in obstructive lung diseases -- what can we expect?].
AB  - Many countries' guidelines recommend pneumococcal vaccination for patients
      suffering from obstructive airway disease. This paper reviews the literature as
      to immunogenicity and safety of this immunization. There is no evidence for a
      negative effect of pneumococcal vaccination on these patients. Only a few data
      exist on the preventive impact of pneumococcal vaccination as to exacerbations of
      obstructive airway diseases. Existing studies mostly took up this question as a
      side aspect. The effect in children and adults appears limited. On the other
      hand, the pneumococcal conjugate vaccine prevents life-threatening invasive
      infections in children younger than 5 years, and pneumococcal polysaccharide
      vaccine protects healthy adults against bacteriaemic pneumonia. Thus,
      pneumococcal vaccination of patients suffering from obstructive airway disease is
      recommendable.

PMID- 15731960
TI  - [Screening for bronchial carcinoma -- pro].

PMID- 15731961
TI  - [Screening for bronchial carcinoma -- contra].

PMID- 15731962
TI  - [Sleep apnea: significance in patients with heart failure. Pathophysiology,
      diagnosis and treatment].

PMID- 15731963
TI  - [Thrombocytopenia during digoxin administration?].

PMID- 15731964
TI  - [Systemic mastocytosis].

PMID- 15731965
TI  - International adoption: a health and developmental prospective.
AB  - Adoptions from international countries have become an option for many US
      families, with over 150,000 children adopted in the past 14 years. Typically,
      internationally adopted children present with a host of medical and developmental
      concerns. Issues such as growth stunting, abnormal behaviors, and significant
      delays in motor, speech, and language development are likely directly related to
      the prenatal and early postnatal environment experienced prior to adoption. The
      new family and its health-care team must quickly work to identify and address
      these issues to aid the child's integration into his or her new family. This
      article will examine potential issues seen in children who are being adopted,
      including the impact of early environment on subsequent development. We will
      summarize early and long-term medical issues and review the extent of
      developmental delays seen in children adopted internationally. Finally, we will
      discuss possible mechanisms leading to the observed delays, including the impact
      of stress on subsequent development. By understanding the extent of expected
      delays and the mechanisms likely causing the issues, the health-care team will be
      in a good position to quickly identify and develop intervention protocols that
      will foster the child's assimilation into his or her new family.

PMID- 15731966
TI  - New arrivals: speech and language assessment for internationally adopted infants
      and toddlers within the first months home.
AB  - Speech-language pathologists are increasingly requested to assess development in
      newly arrived internationally adopted children. These infants and toddlers
      typically arrive home with developmental delays and a lack of proficiency in any
      language, making it difficult to make objective service delivery decisions. This
      article reports the results of speech and language assessments for a group of 28
      children aged 12 to 24 months who were newly adopted from Eastern Europe. Most of
      the children did well, with average English language standard scores within
      normal limits on the Communication and Symbolic Behavior Scale-Developmental
      Profile. The majority of children were also rapidly learning to understand and
      produce English words as measured on the MacArthur-Bates Communicative
      Development Inventory. These findings were used to develop peer-based infant
      toddler guidelines for early speech and language intervention. Using these
      guidelines, 65% of the internationally adopted children did not require early
      intervention, 7% were borderline and recommended for follow-up assessments within
      2 to 3 months, and 28% were recommended for speech and language early
      intervention.

PMID- 15731967
TI  - Early language growth in children adopted from China: preliminary normative data.
AB  - Normative data on English language development in children adopted from China are
      needed to determine whether a child's language skills are within normal limits or
      significantly delayed relative to his or her peers who are other children adopted
      from China. A longitudinal survey of children adopted from China, modified from a
      similar survey used by Glennen and Masters (American Journal of Speech-Language
      Pathology 2002;11:417-433) with children adopted from Eastern Europe, was used to
      collect information on English language development from over 150 children at 3
      month intervals. Preliminary results are presented here, based on 808 surveys
      from 141 children grouped by age at time of adoption. In general, children
      adopted at older ages used more words and produced longer sentences at each 3
      month interval postadoption, but had further to go to "catch up" to norms for
      nonadopted monolingual English-speaking peers of the same age. Individual
      profiles illustrate the variation seen within groups, with some children
      performing at or above age level and others showing varying levels of "delay"
      relative to nonadopted monolingual English-speaking peers and/or adopted peers.

PMID- 15731968
TI  - Adoption age effects on english language acquisition: infants and toddlers from
      China.
AB  - Children adopted from China represent the single largest group of internationally
      adopted children in this country. Because the adoptive families typically do not
      speak any Chinese language or dialect, most of these children experience an
      abrupt shift in their language environment. How age of adoption affects the
      course of English language development of children adopted from China is the
      focus of this study. All of the children in this study were either infants or
      toddlers at the time of adoption and all came from the same orphanage. The
      results showed that the older children (toddlers) were at both an advantage and a
      disadvantage when it came to English language development. The advantage of being
      older was that they learned faster. The disadvantage of being older was that
      there was more for them to learn to become age-appropriate in their English
      language development. There was, however, no evidence to suggest that the
      language switch from a Chinese- to an English-language environment was a
      formidable obstacle for either the infants or the toddlers.

PMID- 15731969
TI  - Starting over: a preliminary study of early lexical and syntactic development in
      internationally adopted preschoolers.
AB  - To explore early language acquisition in internationally adopted preschoolers, we
      collected parental reports (CDI-2) and speech samples from 14 children adopted
      from China between the ages of 2 years, 7 months and 5 years, 1 month. Their
      lexical and syntactic development was qualitatively similar to infants acquiring
      English as a first language: nouns and social words dominated early vocabularies;
      verbs and closed-class items became more frequent as vocabulary size increased;
      and lexical and syntactic development were tightly correlated. This research has
      several implications for clinicians. First, it demonstrates that parental reports
      provide valid information during the first year after adoption and could be
      useful in identifying preschool children in need of further assessment. Nine to
      15 months after arrival many children reached the ceiling of the CDI-2,
      suggesting that this instrument has limited utility after the first year.
      Finally, the rapid lexical and syntactic growth of these children suggests that
      many of them may eventually catch up with their native-born peers.

PMID- 15731970
TI  - Phonological skills of children adopted from China: implications for assessment.
AB  - Little is known about the acquisition of English phonology by children adopted
      from China. Data are summarized from three recent studies with a focus on the
      phonological skills of children adopted from China as infants or toddlers. Two
      longitudinal studies (combined n = 8) described early phonological behaviors
      (e.g., babbling, phonetic inventories), and found substantial individual
      variation. In spite of this variation by 3 years of age, nearly all of the
      children were performing at a level comparable to nonadopted monolingual English
      speaking peers. No clear relationship between the early behaviors and outcome at
      age 3 was found. The third study provided descriptions of the phonological skills
      of preschoolers ( n = 25) who had been adopted 2 or more years earlier, and found
      that only a few had persistent phonological delays. Errors were predominantly
      common developmental errors frequently observed in nonadopted monolingual English
      speaking children. These findings suggest that tests and measures developed for
      monolingual English-speaking children may be used cautiously with children
      adopted as infants or toddlers who have been in their permanent homes for 2 or
      more years. Prior to that time, assessment should focus on independent analyses
      of phonological behaviors with consideration of the child's chronological age,
      length of exposure to English, and development in other language domains.

PMID- 15731971
TI  - Linguistic interference between L1 and L2 in internationally adopted children.
AB  - Bilingual children learning two languages either simultaneously or successively
      experience patterns of cross-language interference or facilitation due to
      similarities and differences between the languages. Internationally adopted
      toddlers are only truly bilingual for a short period of time because the first
      language disappears quickly after adoption. Yet residual effects of the
      disappearing first language might impact patterns of learning the new language.
      To determine if cross-language patterns affected language learning in very young
      children, language samples were collected from 23 children adopted from Eastern
      Europe between 11 and 23 months of age. Samples were collected at 6-month
      intervals during the first year after adoption, then annually up through age 4.
      Age and order of acquisition of several grammatical morphemes including V + ing,
      articles, contracted and uncontracted copulas, and contracted and uncontracted
      auxiliary were explored. These morphological structures developed in the same
      sequence observed in monolingual children speaking English and were not notably
      impacted by cross-linguistic factors from language 1. Guidelines for
      professionals and parents are discussed.

PMID- 15731972
TI  - Continued catch-up and language delay in children adopted from China.
AB  - Most internationally adopted children learn their new language rapidly after
      adoption. What is not known is whether these gains continue at the same
      developmental pace throughout the preschool years. To answer this question, the
      continued language development of the 10 lowest performers from a cohort of 55
      preschool-aged children adopted from China was examined. All 55 children had
      originally been assessed approximately 2 years earlier as preschoolers. The
      purpose was to examine whether continued English language exposure resulted in
      greater gain scores on a battery of standardized speech-language tests normed on
      monolingual English speakers. The 10 lowest performers were retested on the same
      battery approximately 2 years later. Scores on the second testing were examined
      in two ways. First, the amount of gain made from first to second testing for each
      child was examined, and second, the low performers were compared with adopted
      children from the original cohort who were matched for age and duration of time
      in the United States. It was found that more than half of the low-scoring
      children made clinically significant gains on the second assessment, but that low
      performers as a group scored below the level of matched peers in the cohort, even
      after approximately 2 years of additional English language exposure.

PMID- 15731973
TI  - Five years later: language in school-age internationally adopted children.
AB  - This study followed a cohort of 46 school-age children adopted from Eastern
      Europe who were originally studied by Glennen and Masters up through age 2 or 3.
      Five years later, the children were 6 to 9 years of age. Data on their school-age
      abilities were collected through surveys of parents and teachers. Parents
      indicated that 17.4% of the children were receiving classroom accommodations or
      special education programs and 54.5% had one or more diagnoses. The most common
      diagnosis was attention deficit disorder/attention deficit hyperactivity disorder
      (ADD/ADHD), occurring in 25% of the children, primarily boys. Learning disability
      and speech language impairment were each noted in 11.4% of the children. Language
      and Social Skill profiles on the Children's Communication Checklist-2 and Social
      Skills Rating Scale (SSRS) indicated that structural and meaning-based language
      abilities were areas of strength. Measures of pragmatic use of language (i.e.,
      Use of Context, Social Relations, Nonverbal Communication) were relative
      weaknesses. Behavior profiles on the SSRS indicated higher than average levels of
      hyperactivity. The profile of Language and Social Skills strengths and weaknesses
      was similar to patterns observed in children with ADD/ADHD. Age of adoption was
      not predictive of school-age outcomes on these measures, but the children's
      expressive vocabulary when they were 2 to 3 years of age predicted SSRS outcomes
      for Social Skills and Problem Behaviors.

PMID- 15731974
TI  - [Quality measurement between illusion and reality--is the quality of medical care
      measurable?].
AB  - The current implementation of external quality assurance focuses on identical,
      albeit simple univariate procedures. This approach proves to be inefficient,
      exhibiting low specificity. Definitions of performance indicators were classified
      by the local steering committee and applied to Bavarian obstetric data augmented
      with multivariate and confidence interval analyses as well as statistical
      simulations. A highly selected group of units with multivariate extreme values
      was audited. Blind application of federal regimes without further in-depth
      analysis of concomitant data is inefficient and may lead to wrong conclusions.
      Exclusive univariate analyses of performance indicators are not enough.
      Multivariate analyses have a higher specificity. Classification reveals an
      imbalance in the indicator set with respect to varying degrees of coverage as
      well as a bias towards outcome. Deficiencies in the organisational processes
      crucial for quality of care are often only revealed by dedicated cause and effect
      analyses within the hospital, thus constituting an essential prerequisite for
      desired changes in health care policies. It is unlikely that mere publication of
      performance indicators in the impending quality report will generate lucidity in
      spite of abundant structure. The installation of standardised programmes with
      identical computation rules may appear convincing as long as no doubt is cast
      upon the efficacy of the performance indicators in respect to their intended
      usage as well as upon the expected feedback effects. The experience so far
      however teaches us that these elements may be essential yet although not
      sufficient.

PMID- 15731975
TI  - [Can data from quality assurance programs such as peri-/neonatal compilations be
      used for secondary epidemiological studies?].
AB  - BACKGROUND: The aim of this study was to explore whether population-based data
      from a regional quality control program can be utilized to compare the neonatal
      outcome of small for gestational age (SGA) and appropriate size for gestational
      age (AGA) new-borns. METHODS: The Center for Quality Management in Health Care
      maintains perinatal data for almost all births in Lower Saxony (Germany).
      Neonatal data are collected for all infants admitted to hospital within 10
      postnatal days. We evaluated linked perinatal and neonatal datasets of 4126 very
      low birthweight infants (VLBW; < 1500 g), born in 1991 - 1996. After checking for
      completeness, representativeness, and validity, exclusion criteria were defined
      to minimize bias and to yield similar proportions of SGA- and AGA-neonates. Since
      inclusion of all multiple births would lead to an overestimation of maternal risk
      factors, one sibling was randomly selected from each set of multiples. Bias
      arising from not well defined study populations should be shown based on
      univariable mortality analyses (Kaplan-Meier survival curves). RESULTS:
      Application of exclusion criteria resulted in a final study population of 1623
      independent (disjunctive) new-borns from 25 - 29 weeks gestation, 173 of whom
      were SGA, 1450 AGA. Kaplan-Meier curves from the initial study population and the
      well defined study base differed significantly. Trend analysis revealed a
      significant (p < 0.05) increase in proportions of both VLBW (from 0.95 % in 1991
      to 1.11 % in 1996; + 17 %) and SGA infants (from 22.7 % to 27.4 %; + 21 %) within
      the observational period. A well defined data selection process is necessary if
      data collected for other purposes are to be used for epidemiological studies.
      Neglecting this labour-intensive work may be one reason for the varying results
      on the outcome of SGA and AGA infants.

PMID- 15731976
TI  - [Integrated psychological parental assistance in the neonatal intensive care
      unit: concepts and first experiences].
AB  - BACKGROUND AND HYPOTHESIS: Psychosocial support programs have been established in
      view of the burden caused to parents having their newborn admitted to the
      neonatal intensive care unit (NICU). Due to limited resources, preventive
      programs can only be offered to parents who are identified by the staff to be at
      risk. Based on the results of a parent questionnaire, the University Children's
      Hospital Vienna has developed a standardized concept of integrated psychological
      support. The program and first results are presented. PATIENTS AND METHODS: The
      psychological support is offered to parents of newborns admitted to the neonatal
      intensive care unit. The aim of the support is to avoid later psychosocial
      problems for child and parents. In an interdisciplinary collaboration, the
      psychologist facilitates parent-child bonding, family development and coping with
      the baby's illness. The standardized psychological support consists of a
      consultation at the beginning and end of the hospital stay. Parents are offered
      optional psychological support or intensive assistance. RESULTS: Parents from 152
      patients received the standardized basic psychological support. The majority of
      the parents took advantage of the additional optional assistance. Because of
      external transfers (42.1 %) or infant death (18.4 %), only 39.5 % of the parents
      could be accompanied until discharge. CONCLUSIONS: A standardized psychological
      model provides parents with the psychological support as one important part of
      the overall concept of neonatal treatment. Additionally, the medical and nursing
      staff were sensitized to psychological factors. An effective psychosocial
      prevention requires psychological support as an essential part of intensive
      neonatal care.

PMID- 15731977
TI  - [Influence of prophylactic information on the frequency of baby blues].
AB  - BACKGROUND: Baby blues, a mood alteration, occurs in 30 to 80 % of the women
      during the first two weeks after childbirth. We evaluated if the frequency of
      baby blues can be influenced by oral and written information about these mood
      alterations. We wanted to find out whether information about postpartum
      depression could make these woman realize their own possible depression and
      therefore seek professional help more rapidly. PATIENTS AND METHODS: In a
      prospective randomized study German-speaking women were randomized on the second
      or third day after childbirth in our institution into an "information group" and
      a "control group". The first group was given oral and written information about
      baby blues and postpartum depression. Both groups were evaluated by Edinburgh
      Postpartum Depression Scale (EPDS) translated into German 3 days, 6 weeks and 3
      months postpartum, by a visual-analogue questionnaire covering the first 6 weeks
      and by a self-report covering the whole period postpartum after 3 months.
      RESULTS: We obtained valuable information from 169 women. Only 12 (15 %) women of
      the "information group" experienced a baby blues vs. 25 (29 %) of the "control
      group" (RR 0.55, P = 0,027, CI 0.28 - 0.93). Concerning postpartum depression, no
      significant difference could be seen. The percentage of scores above 11 in the
      EPDS around birth was 8.5 % vs. 9.3 % in the information vs. control group. 6
      weeks after birth the percentages were 7.5 vs. 7.1 % and 12 weeks after birth
      they were 7.3 % vs. 8.0 %. Of the women considering themselves as depressive by
      self evaluation 3 months postpartum, only a few sought help from a specialist: 7
      of 13 in the Information vs. 4 of 14 in the control group. The difference is not
      statistically significant. CONCLUSION: We conclude that oral and written
      information about baby blues given postpartum can be an effective instrument to
      lower its frequency. No difference in postpartum depression could be registered -
      either in prevalence or in seeking professional help.

PMID- 15731978
TI  - [Perinatal outcome of premature infants weighing less than 1500 g].
AB  - BACKGROUND: Prematurity is a main issue in modern obstetrical care. The purpose
      of the present study was to evaluate the perinatal outcome of premature infants
      weighing less than 1500 g according to the mode of delivery. PATIENTS AND
      METHODS: 122 patients with infants weighing less than 1500 g were enrolled in
      this retrospective study (26 to 32 weeks of gestation). The perinatal outcomes of
      26 infants born by vaginal delivery were compared to 96 infants delivered by
      caesarean section. RESULTS: The rates of rupture of membranes, preterm labour and
      intravenous tocolysis were significantly increased in patients after vaginal
      delivery. Preeclampsia and pathological cardiotocograms were increased in
      patients after caesarean section. Infants born by vaginal delivery showed a
      significant increase of peri- and intraventricular haemorrhage grade III,
      periventricular leukomalacia, C-reactive protein 24 hours postpartum and
      mortality until the seventh day of life. However, the rate of bronchopulmonary
      dysplasia was significantly increased in infants born by caesarean section (p <
      0.05). CONCLUSIONS: These data suggest that the mode of delivery affects the
      perinatal outcome of infants weighing less than 1500 g. Based on the results of
      the present study, it appears unclear which mode of delivery should be preferred,
      depending on particular material and fetal factors.

PMID- 15731979
TI  - [Combination therapy for fetal supraventricular tachycardia with flecainide and
      digoxin].
AB  - Persistent fetal supraventricular tachycardia (SVT) with more than 210 bpm
      frequently leads to congestive heart failure. We report on a case with SVT and
      congestive heart failure that converted into sinus rhythm within 19 days of
      therapy with flecainide and beta-acetyldigoxin. A 32-year-old II gravida I para
      (25 + 1 weeks of gestation) presented with fetal SVT of 267 bpm. A non
      immunologic hydrops fetalis was diagnosed by ultrasound showing ascites, pleural
      and pericardial effusion and tricuspid regurgitation. Within 19 days of
      combination therapy with flecainide and digoxin, cardioversion was achieved.
      After 36 days of therapy no more signs of cardiac failure could be detected. A
      healthy boy was born at 38 + 6 weeks of gestation. Although cardioversion is
      expected after 72 h of therapy according to the literature, this fetus converted
      into sinus rhythm on day 19 of therapy. This indicates that patients should not
      be considered resistant to treatment within the first 3 - 4 days.

PMID- 15731980
TI  - [Magnetocardiography--a possible supplementary method for early detection of
      fetal distress in high-risk pregnancies].
AB  - Ever since the first report on fetal magnetocardiography by Kariniemi in 1974
      numerous studies have examined cardiac activity in healthy fetuses using this
      technique. Recently there has been an increase in reports on the identification
      of fetal pathological states, in particular in the diagnosis of fetal
      arrhythmias, using magnetocardiography. Other possible applications of this non
      invasive method include the assessment of intrauterine growth retardation and
      fetal stress. In a patient with gestational hypertension and asymmetric growth
      retardation without pathological ultrasound findings, fetal magnetocardiography
      showed a reduced beat-to-beat heart rate variability indicating signs of fetal
      stress. On the day following the magnetocardiographic recording, fetal Doppler
      ultrasonography findings indicated an incipient brain sparing effect. The fetal
      growth retardation was reflected in the duration of the fetal cardiac time
      intervals. We conclude that fetal magnetocardiography non-invasively enables the
      timely identification of pathological fetal conditions.

PMID- 15731982
TI  - Premature rupture of the membranes: a cause for neonatal osteomyelitis?
AB  - Osteomyelitis is rare in the neonatal period. Many etiologic factors for causing
      neonatal osteomyelitis have been discussed in the literature; however, premature
      rupture of the membranes has never been emphasized. We report on a neonate with
      osteomyelitis of the right humerus infected with an uncommon pathogen, Klebsiella
      pneumonia. In the absence of any perinatal disease, premature rupture of the
      membranes was suggested to be the cause of the illness. The infant was initially
      regarded as having Erb palsy because of the absence of systemic symptoms and lack
      of perinatal high-risk factors. Antibiotic administration was delayed for 3
      weeks. Luckily, nearly complete recovery was noted after 2 months of follow up.
      We emphasize the importance of considering osteomyelitis in a newborn infant with
      limb palsy, particularly in the presence of premature rupture of the membranes of
      the mother. We also discuss the results of the microbial examination and
      significance of magnetic resonance imaging in neonatal osteomyelitis.

PMID- 15731983
TI  - Chiari I malformation with or without syringomyelia and pregnancy: case studies
      and review of the literature.
AB  - Women with Chiari I malformation with or without syringomyelia are of particular
      concern because of the potential risk of increased intracranial pressure during
      pregnancy and delivery. The following questions are most often asked in the
      clinical setting: Is it safe to have a planned pregnancy? Will the symptoms
      become worse or recur during pregnancy and will the baby be normal? Seven
      patients with Chiari I malformation, with and without syringomyelia, submitted
      checklists of self-reported symptoms experienced during pregnancy, labor, and
      postpartum. Seven patients with Chiari I malformation with and without
      syringomyelia were queried for symptoms during pregnancy, labor, and postpartum.
      None of the patients reported significant increase or recurrence of Chiari
      related symptoms during delivery or postpartum. Four of the women had epidural
      anesthesia for delivery and reported no related symptoms. This series represents
      a small number of women with Chiari I malformation who had uncomplicated
      pregnancy, labor, and delivery.

PMID- 15731984
TI  - Continuous indomethacin infusion may be less effective than bolus infusions for
      ductal closure in very low birth weight infants.
AB  - The effectiveness of continuous indomethacin (INDO) infusion versus bolus
      infusions for closure of patent ductus arteriosus (PDA) was investigated. The
      study design was an open-label case series (continuous INDO) with historic
      controls matched for gestational age (bolus INDO). Ductal closure rates were
      determined in two groups: 16 preterm infants with PDA treated with continuous
      INDO infusion (CONTIN group) and 16 control patients, matched for gestational
      age, who received bolus INDO infusions (BOLUS group). The total dosage was the
      same for both groups. PDA closed in seven of 16 preterm infants in the CONTIN
      group and in 13 of 16 in the BOLUS group ( p = 0.033, Fisher's exact test). In
      infants < 1000 g it was two of eight in the CONTIN group and 10 of 10 in the
      BOLUS group ( p = 0.002). Continuous INDO infusion was more likely than bolus
      infusion to be associated with failure of ductal closure (odds ratio, 19; 95% CI,
      1.5 to 247; p = 0.023). This indicates that continuous infusion of INDO may be
      less effective in closing PDA than bolus infusions, especially in extremely low
      birth weight infants.

PMID- 15731985
TI  - Effect of decreased use of postnatal corticosteroids on morbidity in extremely
      low birthweight infants.
AB  - The objective of this study was to evaluate the effect of decrease in use of
      postnatal corticosteroids on duration of assisted ventilation and hospital stay
      of extremely low birthweight infants. All infants born between January 1, 1999,
      and December 31, 2000, and with birthweight </= 1000 g were included if they
      survived to be discharged home. Postnatal corticosteroids use in these infants
      decreased from 44% in 1999 (group 1) to 13% in 2000 (group 2; p = 0.002). The
      mean duration of assisted ventilation was similar in the two groups (20.6 +/-
      19.7 versus 24.5 +/- 22.2 days; p = 0.4), as was the mean duration of hospital
      stay (82.2 +/- 23.5 versus 85.1 +/- 30.5 days; p = 0.6). The incidence of late
      onset bacterial sepsis was significantly lower among group 2 infants (17% versus
      40%; p = 0.02).

PMID- 15731986
TI  - Effects of nuchal cord on birthweight and immediate neonatal outcomes.
AB  - Our objective was to ascertain if nuchal cord is associated with adverse neonatal
      outcomes. Using a retrospective database of term neonates, outcomes were compared
      among infants with 0, 1, and 2 or more loops of cord encircling the neck. Of 4426
      neonates, 3651 served as controls, 691 had one loop, and 84 had two or more
      loops. There were no significant differences in the mean birthweight, the
      frequency of nonreassuring fetal heart rate patterns, operative vaginal
      deliveries, or 5-minute Apgar scores of < 7. The cesarean delivery rate was
      significantly different among the three groups and was the highest among the
      group of women whose fetus had no nuchal cord ( p < 0.01). A nuchal cord at term
      is not associated with untoward pregnancy outcomes.

PMID- 15731987
TI  - Pregnancy outcome following exposure to permethrin and use of teratogen
      information.
AB  - NIX is a 1% permethrin creme rinse used for the treatment of head lice. There are
      no studies regarding human exposure during pregnancy. The primary objective of
      this study was to examine the safety of permethrin exposure during pregnancy. The
      secondary objective was to examine how teratogen information is perceived and
      used by women who requested information regarding this product. Women who had
      called the Motherisk and MotherSafe Programs to inquire about exposure to
      permethrin during pregnancy were followed-up to ascertain the outcome of their
      pregnancies. These women were compared with another group who had not been
      exposed to any known teratogenic drugs. Women who decided not to use permethrin
      were administered an additional questionnaire. We enrolled 147 women and
      completed outcomes on 113 pregnancies of women who had used permethrin some time
      during their pregnancy. There were 106 live births, six spontaneous abortions,
      one therapeutic abortion, and one major malformation in the women who used
      permethrin in the first trimester. The mean birthweight was 3540 +/- 492 g and
      the mean gestational age was 40 +/- 1 weeks. There were no statistically
      significant differences between the exposed and comparison groups in any of the
      pregnancy outcomes. Of the 34 women who chose not to use permethrin and who
      completed the additional questionnaire, 18 (52%) did not use permethrin because
      they did not feel the information was sufficiently reassuring. The results of
      this study suggest that the use of permethrin products during pregnancy appears
      to be relatively safe because there was no increase in the rates of major
      malformations. We also found that some women will not use a product during
      pregnancy unless they can receive a 100% guarantee that it will not harm their
      baby.

PMID- 15731988
TI  - Left ventricular myocardial performance in the fetus with severe tricuspid valve
      disease and tricuspid insufficiency.
AB  - We sought to determine whether left ventricular (LV) function is abnormal in a
      fetus with severe tricuspid valve disease (TVD), and whether it may contribute to
      the outcome. We measured the LV Tei index (including isovolumic relaxation [IRT],
      contraction, and ejection times) in 31 fetuses with TVD, compared the data with
      measurements from 32 normal fetuses, and correlated these measurements with
      pulmonary morphology and outcome. LV Tei index was significantly greater,
      ejection times shorter, and IRT longer in TVD compared with controls. The Tei
      index was highest in fetuses with either pulmonary insufficiency or atresia
      compared with those with forward flow. Finally, LV Tei index was significantly
      greater in fetuses with fetal (n = 5) or neonatal (n = 9) demise than in neonatal
      survivors (n = 7). Global LV performance as assessed by the Tei index is abnormal
      in TVD and likely contribute to the high mortality associated with TVD.

PMID- 15731989
TI  - Ultrasonographic findings of facial dysmorphism in Wolf-Hirschhorn syndrome.
AB  - Wolf-Hirschhorn syndrome has characteristic craniofacial dysmorphism with severe
      fetal growth restriction. We present a case that revealed facial dysmorphism
      characteristic of Wolf-Hirschhorn syndrome with two- and three-dimensional
      ultrasonography. The facial dysmorphic features in the present case were
      dolichocephaly; high forehead; large rectangular nose continuing to the eyebrows;
      hypertelorism; short philtrum; carp-shaped mouth; microretrognathia; and large,
      simply modeled, low-set ears. Chromosome analysis of amniotic fluid cells was
      46,XX,del(4)(p15.2), confirming the ultrasonographic result. Examination with two
      and three-dimensional ultrasonography is useful to observe the face of fetuses
      with severe intrauterine growth restriction to diagnose multiple congenital
      anomaly syndromes.

PMID- 15731990
TI  - Maternal and fetal tuberous sclerosis complicating pregnancy: a case report and
      overview of the literature.
AB  - Tuberous sclerosis complex (TSC) is an autosomal-dominant phakomatosis that can
      result in cardiac and central nervous system lesions and may adversely impact
      fetal and maternal health. We report a case of a 19-year-old primagravida with
      TSC whose pregnancy was complicated by preeclampsia, preterm labor, and fetal
      demise. The fetus, also affected with TSC, was diagnosed with a cardiac
      rhabdomyoma on ultrasound at 24 gestational weeks and intracranial tubers on
      fetal magnetic resonance imaging at 26 gestational weeks. Hydrops fetalis
      developed in the 30th gestational week. Fetal demise occurred during induction of
      labor. A systematic review of the medical literature was conducted. Our objective
      was to quantify maternal and fetal morbidity and mortality associated with TSC.
      We identified 36 additional cases of fetal TSC with cardiac rhabdomyoma diagnosed
      prenatally. Including our case, we also identified 23 pregnancies (17 mothers)
      complicated by maternal TSC. Rates of complications are calculated. We conclude
      that pregnancies complicated by maternal or fetal TSC deserve careful vigilance.
      Although benign histologically, cardiac rhabdomyomas can result in fetal
      morbidity and mortality.

PMID- 15731991
TI  - Postpartum retroperitoneal fasciitis: a case report and review of literature.
AB  - We present a case of a postpartum female with iliopsoas fasciitis in the
      puerperium. Two days after a spontaneous vaginal delivery at 38 weeks without any
      complications, the patient complained of pain in the left thigh and hip,
      associated with a temperature of 38 degrees C. Consequently, she could not walk 4
      days after delivery and her body temperature had increased to 39 degrees C.
      Extreme left flank pain and tenderness in the left pelvic wall were prominent,
      whereas the tenderness in the pelvis was moderate. Magnetic resonance imaging led
      us to diagnose iliopsoas fasciitis. This was complicated by sepsis but improved
      after a protracted antibiotic treatment without any surgical intervention. A
      literature review revealed that serious complications, including sepsis or
      permanent functional disturbance, could arise although retroperitoneal fasciitis
      and/or abscesses are very rare after vaginal delivery. Iliopsoas fasciitis could
      be considered when patients complain of extreme pain in the pelvic wall,
      sacroiliac joint region, or thigh-symptoms that are uncommon in uncomplicated
      endometritis.

PMID- 15731992
TI  - Risk factors of retinopathy of prematurity in premature infants weighing less
      than 1600 g.
AB  - There are many risk factors contributing to retinopathy of prematurity (ROP).
      Some are still controversial, including the use of glucocorticoid and
      intraventricular hemorrhage. Hence, a retrospective study was performed to
      evaluate the association between the suspected risk factors and ROP in a medical
      center in southern Taiwan. One hundred fifty-nine infants with birth body weight
      < 1600 g admitted to our neonatal intensive care unit before the 29th day of life
      were enrolled into this study. Clinical data were analyzed by means of logistic
      regression. The prevalence of ROP in all infants (birthweight < 1600 g) is 36.48%
      (58 of 159) and 59.46% (22 of 37) in extremely low birthweight infants
      (birthweight < or = 1000 g). One infant with gestational age 32 weeks and
      birthweight 1420 g developed stage III ROP. Logistic regression revealed six
      factors to be significant variables. Birthweight < or = 1000 g, intraventricular
      hemorrhage, sepsis, and use of glucocorticoid or dopamine were risk factors
      associated with higher incidence of ROP. Supplementation of vitamin E was shown
      to relate to lower incidence of ROP. This study confirms several risk factors
      recognized in previous statistical analyses. Sepsis is the most significant
      factor contributing to ROP. Vitamin E was proven to be effective in prophylaxis
      of development of ROP. The possibility of development of ROP could not be
      excluded in infants with gestational age > 32 weeks.

PMID- 15731994
TI  - Acute hepatitis C: a multifaceted disease.
AB  - Although acute hepatitis C virus (HCV) infection is a rare disease and typically
      not associated with severe clinical symptoms, it has become a disease of
      significant interest for clinical investigators, virologists, and immunologists
      alike. In the same way that acute hepatitis C provided a window of opportunity
      for understanding the clinical and virological aspects of HCV infection as the
      field was being established, it is now clear that it can provide a window into
      further understanding the early interaction of the virus with the host immune
      response. The acute phase of infection is usually considered to be the first 6
      months; however, rather than defining acute HCV by the time that has passed after
      initial infection, it can also be defined as the biological state in which
      spontaneous clearance is still possible.

PMID- 15731995
TI  - Management and treatment of injection drug users with hepatitis C virus (HCV)
      infection and HCV/human immunodeficiency virus coinfection.
AB  - Injection drug use is the major mode of hepatitis C virus (HCV) transmission in
      developed countries. Despite this, relatively few current and recovering
      injection drug users (IDUs) have received HCV treatment. Studies among
      individuals with a recent history of injection drug use or those receiving drug
      dependency treatment have provided evidence that these groups can be successfully
      treated for chronic HCV infection. These studies have provided the impetus to
      change guidelines for treatment of current and recovering IDUs, with a move
      toward individualized HCV treatment assessment and the removal of defined periods
      of illicit drug use abstinence. Strategies to improve access to HCV treatment for
      current and recovering IDUs include drug dependency treatment education and
      training for hepatologists and other HCV treatment physicians, HCV treatment
      education and training for addiction medicine physicians, development of
      multidisciplinary clinics, and peer-based eduction and support for individuals
      considering and receiving HCV treatment.

PMID- 15731996
TI  - Treatment of chronic hepatitis C in human immunodeficiency virus/hepatitis C
      virus-coinfected patients in the era of pegylated interferon and ribavirin.
AB  - A significant percentage of human immunodeficiency virus (HIV) -infected
      individuals are also infected with the hepatitis C virus (HCV). With the much
      improved survival of HIV-infected patients through the use of highly active
      antiretroviral therapy, liver disease caused by coinfection with HCV has emerged
      as a significant threat to the health and survival of persons with HIV disease.
      HIV/HCV-coinfected patients with ongoing HIV viremia have a faster rate of HCV
      related liver fibrosis progression and a more rapid progression to liver failure
      or hepatocellular carcinoma than HCV-monoinfected persons. In contrast to the
      deleterious effect of HIV on HCV-related liver disease, most studies have shown
      that HCV does not influence progression of HIV infection to AIDS or death. HCV
      therapy with peginterferon alfa (2a or 2b) plus ribavirin can achieve a sustained
      viral response in HIV/HCV-coinfected patients of up to 38% in HCV genotype 1 and
      up to 73% in genotypes 2 and 3. The safety profile is largely similar to therapy
      in HIV-monoinfected patients, but there is a higher incidence of mitochondrial
      toxicity in patients taking didanosine or stavudine and of anemia in patients
      taking zidovudine. There is no proven anti-HCV therapy for HIV/HCV-coinfected
      patients with end-stage liver disease (ESLD). Liver transplantation is being
      investigated as a potential therapeutic option for HIV-infected individuals with
      ESLD, and initial reports are encouraging. Given that pegylated interferon and
      ribavirin have been shown to be safe and effective for HIV/HCV coinfection as
      well as HCV monoinfection, all HIV/HCV-coinfected patients should be evaluated
      for therapy.

PMID- 15731997
TI  - The liver biopsy in chronic hepatitis C: a view from the other side of the
      microscope.
AB  - The liver biopsy has long been the gold standard for the evaluation of the state
      of liver disease in patients with chronic hepatitis C. Although a liver biopsy
      continues to be a recommended part of the work-up of this disease, its routine
      use is challenged by the increasing effectiveness of therapy and by surrogate
      biochemical tests that give information about the stage of disease. Nevertheless,
      recent studies have shown that histological features other than stage may have
      predictive value for disease progression and therapeutic response to interferon
      based regimens. Pathologists can increase the relevance and utility of the liver
      biopsy in chronic hepatitis C by the systematic reporting of steatosis and iron
      accumulation in addition to stage and grade, and by identifying certain potential
      confounding liver diseases, such as steatohepatitis and hereditary
      hemochromatosis. Clinicians can then make best use of the information derived
      from the liver biopsy to help them advise patients on the natural history of
      their disease and the therapeutic options that are available.

PMID- 15731998
TI  - Treating chronic hepatitis C in the primary care setting.
AB  - The National Institutes of Health and other institutions have emphasized the need
      to expand access to treatment of chronic hepatitis C virus infection to a larger
      and more diverse patient population. To begin to address this need, the divisions
      of General Internal Medicine and Liver Diseases of the Mount Sinai Medical Center
      created a program to identify patients who might benefit from hepatitis C
      treatment, to treat uncomplicated patients in the primary care setting, and to
      refer appropriate patients to liver disease specialists. Preliminary data from
      this program suggest that primary care-based treatment of chronic hepatitis C may
      offer unique advantages. The primary care setting allows special needs to be
      addressed and allows comprehensive services to be provided. Patients are guided
      through the complex pretreatment evaluation process, and non-liver-related
      comorbidities are managed. Our program may provide a useful model for increasing
      hepatitis C literacy among primary care providers and for extending treatment to
      a broader population of patients with hepatitis C.

PMID- 15731999
TI  - Current and future concepts in hepatitis C therapy.
AB  - The goal of hepatitis C virus (HCV) therapy is permanent viral eradication. This
      requires the use of drug combinations with multiple modes of action. Steady-state
      HCV replication kinetics can be disrupted by drugs that inhibit virus production
      (antiviral molecules), inhibit de novo cell infection, and/or accelerate the
      clearance of infected cells. Pegylated interferon-alpha and ribavirin combine all
      of these mechanisms of action when used together, yet fail to clear HCV from a
      significant number of patients. New therapeutic approaches are needed. The next
      generation of anti-HCV therapeutic agents will fall into four main categories:
      new interferons and interferon inducers, alternatives to ribavirin, specific HCV
      inhibitors, and immune therapies. Ideally, these new treatments will increase the
      rate of sustained viral eradication and improve tolerability and acceptability.
      Drug combinations will be tailored to the individual patient, based on baseline
      parameters and viral kinetics during therapy.

PMID- 15732000
TI  - Merging models of hepatitis C virus pathogenesis.
AB  - Chronic hepatitis C virus (HCV) infection is one of the major causes for
      development of liver cirrhosis and end-stage liver disease. This article reviews
      two contrasting models of HCV pathogenesis, discusses the merits of each, and
      presents a rationale for combining the two models into one. Any successful model
      of HCV pathogenesis must explain how the characteristic features of cirrhosis and
      end-stage liver disease arise. These features include the loss of hepatocyte
      function (low serum albumin and reduced clotting ability); the presence of
      regenerative nodules; and the deposition of excessive extracellular matrix
      material, especially collagen (fibrosis), which is associated with the
      transformation of the liver sinusoids to capillary-like structures leading to
      portal hypertension. A successful model should explain several observations about
      the rate of disease progression. HCV is characterized by slow progression of
      fibrogenesis and, importantly, cirrhosis seems to develop only after a long
      latency (and only in a subset of patients). Among the prognostic factors of
      disease progression, the age at infection with the HCV virus and the presence of
      fibrosis appear to be highly relevant in predicting the development of
      progressive fibrosis. Traditional models of HCV pathogenesis propose that
      fibrogenesis is the predominant process. Fibrogenesis is induced by activation of
      fibrogenic cells, such as stellate cells, which results in excessive collagen
      deposition. By altering the normal architecture and vasculature, the collagen
      bands finally lead to cirrhosis and loss of organ function. Activation of
      stellate cells is induced by inflammation, cytokine signaling, and possibly by
      hepatocyte apoptosis. The telomere model of HCV pathogenesis suggests that
      hepatocyte damage plays an essential role in the development of cirrhosis.
      According to this model, hepatocyte damage leads to increased cell turnover, and
      to the accelerated shortening of hepatocyte telomeres. Critical telomere
      shortening leads to hepatocyte senescence, loss of hepatocyte function,
      exhaustion of hepatocellular regeneration, and to a greatly enhanced fibrotic
      response to injury. This review summarizes both models and presents evidence that
      these models are not mutually exclusive but rather can be merged into a
      comprehensive pathogenesis model that outlines the pathway of HCV-induced
      cirrhosis.

PMID- 15732001
TI  - Hepatitis C virus particles and lipoprotein metabolism.
AB  - The majority of infectious hepatitis C particles are present in the low-density
      fractions from plasma of infected patients, suggesting an association of the
      virus with lipoproteins and the use of lipoprotein receptors for cell entry.
      Although classical hepatitis C virus (HCV) virions have been reported by some
      investigators, their role in the HCV life cycle has not been clearly identified.
      Moreover, two other forms of particles have been characterized: low-density lipo
      viro-particles (LVPs) and high-density particles. The latter are nonenveloped
      nucleocapsids that have immunoglobulin G Fcgamma binding capacity. LVPs are
      spherical particles enriched in triglycerides. At a minimum, they contain
      apolipoprotein B, HCV RNA, and core protein. The main source of LVPs is likely to
      be the enterocytes rather than the hepatocytes, suggesting an interaction between
      chylomicron and LVP assembly. In experimental systems, HCV core protein inhibits
      the microsomal triglyceride transfer protein, binds to apolipoprotein AII, and
      induces accumulation of cytoplasmic lipid droplets. A model of LVP and HCV core
      lipid droplet generation is proposed.

PMID- 15732002
TI  - The hepatitis C virus alternate reading frame (ARF) and its family of novel
      products: the alternate reading frame protein/F-protein, the double-frameshift
      protein, and others.
AB  - The hepatitis C virus (HCV) has an alternate reading frame (ARF) that overlaps
      the core protein gene. The overlapping reading frame distinguishes HCV from all
      of its known viral relatives, with the possible exception of GB virus B (GBV-B).
      The ARF is expressed during natural HCV infections and stimulates specific immune
      responses. Like several essential genes in other viruses (e.g., the human
      immunodeficiency virus polymerase) the ARF lacks an in-frame AUG start codon,
      suggesting that its expression involves unusual translation-level events. In
      vitro studies indicate that ribosomal frameshifting may be one of several
      processes that can lead to translation of the ARF. Frameshifting yields chimeric
      proteins that have segments encoded in the core gene covalently attached to amino
      acids encoded in the ARF. A consistent nomenclature for the ARF's protein
      products has yet to be established. We propose that all proteins that contain
      amino acids encoded in the + 1 ARF be called alternate reading frame proteins
      (ARFPs) and that specific ARFPs, such as the ARFP/F-protein, the double
      frameshift protein, and the short form of core + 1, be designated as follows:
      ARFP/F (ARFP/F-protein), ARFP/DF (double-frameshift), and ARFP/S (short form of
      core + 1). The roles of ARFPs in the HCV life cycle are not yet known. There is a
      significant possibility that ARFPs may be responsible for some of the effects
      attributed to the core protein, given that most studies seeking to define the
      function of the core protein have employed materials likely to contain a
      combination of the core protein and ARFPs. The observed effects of the core
      protein include the induction of liver cancer, transformation of cells, and
      alterations of immune responses. This article reviews the discovery of ARF,
      describes the RNA structural elements involved in core/ARF gene expression,
      discusses possible functions of ARFPs, and considers the potential usefulness of
      ARFPs in vaccines. The HCV ARF is the focus of a new and rapidly expanding area
      of research, and the results of many ongoing studies are currently available in
      abstract form only. The preliminary nature of investigations that have not yet
      been reviewed by peers is noted in the text.

PMID- 15732003
TI  - The nervous system and hepatitis C virus.
AB  - Hepatitis C virus (HCV)-associated nervous system disorders have been described
      with increasing frequency in the literature, but definitive conclusions regarding
      their pathogenesis is for the most part lacking. Best established are
      complications due to cryoglobulinemia, vasculitis, and thrombosis, in which focal
      disturbances of peripheral nerve or brain function are seen. Rarer are cases of
      inflammatory encephalitis and/or myelitis similar to other flaviviral infections.
      A body of literature detailing cognitive abnormalities is accumulating; still
      unclear is whether these neuropsychologic effects are due specifically to HCV or
      to other processes associated with HCV infection. HCV has been localized to the
      central nervous system; much of its basic neurobiology remains to be described
      and awaits further correlation with clinical abnormalities.

PMID- 15732004
TI  - [Current aspects of stone therapy].
AB  - More than 30 % of all admissions to an urologic clinic are for the treatment of
      urinary stones. In almost all cases, the treatment is minimally invasive
      employing extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy (URS) or
      percutaneous nephrolithotomy (PCNL). Technical advances in endourology and a
      growing expertise in ESWL led to a decline in ESWL and an increase in endoscopic
      techniques. In comparison with ESWL, the endoscopic techniques are more invasive
      but in most cases achieve a stone free state faster. With the introduction of
      diagnosis related groups (DRG), the economic aspect of stone therapy is gaining
      in importance. Stone prevention leads to a cost reduction in the health care
      system, justifying the use of an appropriate stone metaphylaxis. This review
      article presents the current recommendations for interventional urinary stone
      therapy and lists the options of conducting both medical and economically
      rational therapy.

PMID- 15732005
TI  - [Scrotal diverticulum of the urinary bladder -- rare cause of an inguinal
      hernia].
AB  - INTRODUCTION: Massive herniation of the bladder through the inguinal canal is a
      rare entity. We report on a patient with a large inguinoscrotal herniation of the
      urinary bladder commonly referred as "scrotal cystocele". Diagnostic means and
      therapeutic strategies are discussed. CASE REPORT: After laparoscopic repair of a
      bilateral inguinal hernia, a 60-year-old man described a persistent right groin
      mass that varied in size with the degree of bladder distension. Diagnostic
      evaluation revealed a large bladder diverticulum extending into the right
      scrotum. Treatment consisted of inguinal resection of the bladder diverticulum,
      the peritoneal sack and closure of the hernia. CONCLUSION: Inguinal herniation of
      a large bladder diverticulum has to be considered in the differential diagnosis
      of inguinal hernias, especially in patients with obstructive symptoms of the
      bladder outlet.

PMID- 15732007
TI  - [Uterovesical fistula].
AB  - INTRODUCTION: Uterovesical fistulas belong to the least common types of
      urogenital fistulas. Although uncommon, they cannot be considered a rarity in
      view of about 800 published cases in the literature. They are most frequently
      caused by repeated caesarean sections, which are increasing, and their
      complications can be expected to increase as well. CASE REPORT: During the second
      caesarean section of a 31-year-old woman, the urinary bladder was opened and
      subsequently closed by a urologic surgeon. In the following weeks and months, the
      patient suffers from urinary incontinence in response to bladder filling, cyclic
      hematuria (menouria) and recurrent cystitis. After multiple examinations without
      establishing a diagnosis, an uterovesical fistula was suggested by cystoscopy and
      confirmed by cystography. The fistula, which measured 2 cm in diameter, was
      successfully closed by transperitoneal approach without interposition of omentum.
      CONCLUSION: Uterovesical fistulas are to be expected to increase due to an
      increasing rate of repeated caesarean sections. They can be suggested by their
      typical symptoms, easily diagnosed by imaging examinations and successfully
      treated by transperitoneal closure.

PMID- 15732006
TI  - [Total laparoscopic excision of a leiomyoma of the urinary bladder -- a case
      report].
AB  - INTRODUCTION: Leiomyoma of the urinary bladder is a rare, benign tumor of
      mesenchymal origin. Treatment options are discussed. Besides open surgery and
      transurethral resection of small, submucosal tumors, laparoscopic excision is an
      effective therapeutical option with a low complication rate. CASE REPORT: We
      report the medical history of a 36-year-old woman suffering from a leiomyoma of
      the urinary bladder and the therapy through laparoscopic excision. CONCLUSIONS:
      Laparoscopic removal of urinary bladder leiomyomas is a suitable alternative to
      common therapeutical procedures.

PMID- 15732008
TI  - [Bruch colposuspension].

PMID- 15732010
TI  - Are we really communicating? Standard terminology versus terminology standards in
      veterinary clinical pathology.

PMID- 15732009
TI  - Variation in antiviral 2',5'-oligoadenylate synthetase (2'5'AS) enzyme activity
      is controlled by a single-nucleotide polymorphism at a splice-acceptor site in
      the OAS1 gene.
AB  - It is likely that human genetic differences mediate susceptibility to viral
      infection and virus-triggered disorders. OAS genes encoding the antiviral enzyme
      2',5'-oligoadenylate synthetase (2'5'AS) are critical components of the innate
      immune response to viruses. This enzyme uses adenosine triphosphate in 2'
      specific nucleotidyl transfer reactions to synthesize 2',5'-oligoadenylates,
      which activate latent ribonuclease, resulting in degradation of viral RNA and
      inhibition of virus replication. We showed elsewhere that constitutive (basal)
      activity of 2'5'AS is correlated with virus-stimulated activity. In the present
      study, we asked whether constitutive activity is genetically determined and, if
      so, by which variants. Analysis of 83 families containing two parents and two
      children demonstrated significant correlations between basal activity in parent
      child pairs (P<.0001) and sibling pairs (P=.0044), but not spousal pairs,
      suggesting strong genetic control of basal activity. We next analyzed association
      between basal activity and 15 markers across the OAS gene cluster. Significant
      association was detected at multiple markers, the strongest being at an A/G
      single-nucleotide polymorphism at the exon 7 splice-acceptor site (AG or AA) of
      the OAS1 gene. At this unusual polymorphism, allele G had a higher gene frequency
      in persons with high enzyme activity than in those with low enzyme activity (0.44
      vs. 0.20; P=3 x 10(-11)). Enzyme activity varied in a dose-dependent manner
      across the GG, GA, and AA genotypes (tested by analysis of variance; P=1 x 10(
      14)). Allele G generates the previously described p46 enzyme isoform, whereas
      allele A ablates the splice site and generates a dual-function
      antiviral/proapoptotic p48 isoform and a novel p52 isoform. This genetic
      polymorphism makes OAS1 an excellent candidate for a human gene that influences
      host susceptibility to viral infection.

PMID- 15732011
TI  - SNOMED representation of explanatory knowledge in veterinary clinical pathology.
AB  - BACKGROUND: The Systematized Nomenclature of Medicine (SNOMED) is an established
      standard nomenclature for the expression of human and veterinary medical
      concepts. Nomenclature standards ease sharing of medical information, create
      common points of understanding, and improve data aggregation and analysis.
      OBJECTIVES: The objective of this study was to determine whether SNOMED
      adequately represented concepts relevant to veterinary clinical pathology.
      METHODS: Concepts were isolated from 3 different types of clinical pathology
      documents: 1) a textbook (Textbook), 2) the Results sections of industry
      pathology reports (Findings), and Discussion sections from industry pathology
      reports (Discussion). Concepts were matched (mapped) by 2 reviewers to
      semantically-equivalent SNOMED concepts. A quality score of 3 (good match), 2
      (problem match), or 1 (no match) was recorded along with the SNOMED hierarchical
      location of each mapped concept. Results were analyzed using Cohen's Kappa
      statistic to assess reviewer agreement and chi-square tests to evaluate
      association between document type and quality score. RESULTS: The percentage of
      good matches was 48.3% for the Textbook, 45.4% for Findings, and 47.5% for
      Discussion documents, with no significant difference among documents. Of
      remaining concepts, 40% were partially expressed by SNOMED and 14% did not match.
      Mean reviewer agreement on quality score assignments was 76.8%. CONCLUSIONS:
      Although SNOMED representation of veterinary clinical pathology content was
      limited, missing and problem concepts were confined to a relatively small area of
      terminology. This limitation should be addressed in revisions of SNOMED to
      optimize SNOMED for veterinary clinical pathology applications.

PMID- 15732012
TI  - Frequency and severity of tracheal wash hemosiderosis and association with
      underlying disease in 96 cats: 2002-2003.
AB  - BACKGROUND: Hemosiderophages may be found in feline tracheal wash specimens in
      association with various disease conditions, including heart failure, trauma,
      infection, foreign body migration, lung lobe torsion, pulmonary embolism or
      infarction, neoplasia, and bleeding diathesis. Based on observations in our
      laboratory, we hypothesized that tracheal wash specimens from cats with asthma
      also frequently contain hemosiderophages, even in the absence of other known
      causes of pulmonary hemorrhage. OBJECTIVES: The purpose of this study was to
      determine the frequency and severity of hemosiderosis in tracheal wash fluid from
      cats with various diseases, including asthma. METHODS: Feline tracheal wash fluid
      specimens submitted for cytologic evaluation between March 2002 and August 2003
      were included in the study. One hundred and one specimens from 96 cats were
      examined with both Wright's-Giemsa and Prussian blue stains. Cats were assigned
      to 6 disease categories: feline asthma, pneumonia, pulmonary neoplasia, rhinitis,
      heart disease, and other disorders. Based on the percentage of Prussian blue
      positive macrophages, hemosiderosis was categorized as negative (0%), mild
      (<20%), moderate (21-50%), or marked (>50%). RESULTS: The frequency of tracheal
      wash hemosiderosis in the study population was 63.5% (61/96); hemosiderosis was
      mild (29/96, 30.2%), moderate (22/96, 22.9%), or marked (10/96, 10.4%).
      Hemosiderosis was found in 85.7% (6/7) of cats with rhinitis, 78.6% (11/14) of
      cats with pulmonary neoplasia, 75.0% (27/36) of cats with asthma, 71.4% (5/7) of
      cats with primary or concurrent heart disease, 25.0% (5/20) of cats with
      pneumonia, and 66.7% (12/18) of cats with other disorders. In cats with asthma,
      hemosiderosis was usually mild to moderate and frequently was accompanied by
      increased eosinophils. CONCLUSIONS: The results of this study confirm that
      hemosiderosis is a common finding in tracheal wash specimens collected from cats
      with diverse disease conditions, including feline asthma syndrome.

PMID- 15732013
TI  - Hematologic and biochemical abnormalities indicating iron deficiency are
      associated with decreased reticulocyte hemoglobin content (CHr) and reticulocyte
      volume (rMCV) in dogs.
AB  - BACKGROUND: The ADVIA 120 automated hematology system uses low- and high-angle
      light scatter to determine individual RBC and reticulocyte volume and hemoglobin
      (Hgb) concentration. Current hematologic and biochemical markers of iron status
      in the dog are insensitive, and results may be highly variable, especially in the
      presence of concurrent disease (ie, inflammation, neoplasia). Reticulocyte Hgb
      content (CHr) has proven useful in detecting early iron deficiency and iron
      deficiency masked by concurrent disease in human patients. OBJECTIVES: The
      purpose of this study was to retrospectively investigate the association of low
      CHr and reticulocyte MCV (rMCV) with hematologic and biochemical abnormalities
      indicative of iron deficiency in canine patients. METHODS: Reference intervals
      for CHr and rMCV were established on a population of 362 hematologically-normal
      dogs using standard methods. CBC and serum biochemical results from 833 dogs at
      Colorado State University Veterinary Teaching Hospital were retrospectively
      evaluated. The prevalence of decreased CHr and rMCV values was determined based
      on the reference intervals. Hematologic (HCT, MCV) and biochemical (serum Fe
      concentration, percent saturation of transferrin [% sat]) values were compared
      among dogs with low CHr (n=58), low rMCV (n=50), and control dogs (cohort groups
      from the initial population) using a Fisher exact test. RESULTS: Reference
      intervals were 22.3-27.9 pg for CHr and 77.8-100.2 fL for rMCV. Seven percent
      (n=58) of dogs in the hospital population had low CHr and 6% (n=50) had low rMCV
      based on the reference values. Dogs with low CHr had significantly lower HCT,
      MCV, serum Fe, and % sat values than did control dogs. In addition, dogs with low
      CHr or low rMCV values had a higher frequency of microcytosis, anemia, low serum
      Fe concentration, and low % sat than did control dogs. CONCLUSION: Low CHr and
      low rMCV are associated with hematologic and serum biochemical abnormalities
      indicative of iron deficiency. CHr and rMCV hold promise as noninvasive, cost
      effective measures of iron status in the dog.

PMID- 15732014
TI  - Canine angiosarcoma: cytologic, histologic, and immunohistochemical correlations.
AB  - BACKGROUND: Angiosarcomas (AS) are malignant tumors that arise from vascular
      endothelial cells and are common in dogs. Histologically, AS are markedly
      heterogeneous neoplasms that make interpretation by cytology difficult.
      OBJECTIVE: Our objective was to evaluate the cytologic features of canine AS and
      look for additional diagnostic criteria. METHODS: Cytologic specimens from 19
      histologically and immunohistochemically confirmed cases of canine AS were
      extensively reviewed for cytologic features. We compared cytologic,
      histopathologic, and immunohistochemical findings. RESULTS: Neoplastic cells in
      14 cytology specimens had a high-grade sarcomatous appearance, whereas in 4
      specimens the cells were extremely pleomorphic, ranging from sarcomatous to
      epithelioid. In the remaining case, the neoplastic cells were low grade, spindle
      shaped, and monomorphic. Other relevant cytologic findings were blood
      contamination (18/19 cases), cellular cohesiveness (16/19), punctate cytoplasmic
      vacuolation (19/19), background neutrophilia (11/19) and eosinophilia (5/19),
      erythrophagocytosis (8/19), extramedullary hematopoiesis (8/19), and apoptotic
      leukocytes (14/19). Vasoformative features (ie, pseudoacinar structures) were
      observed in 7 of 19 samples. Histologically, 16 neoplasms had a proliferative
      pattern typical of well-differentiated canine AS. Three tumors were atypical
      poorly differentiated AS; 2 of these had a striking epithelioid pattern and 1 was
      a poorly differentiated spindle cell tumor with focal vascular differentiation.
      Immunohistochemically, tumor cells in 16 cases were positive for both endothelial
      markers tested (Factor VIII-related antigen [FVIII-ra] and CD31 antigen), 2 were
      positive for CD31 only, and 1 was positive for FVIII-ra only. The epithelioid AS
      were negative for cytokeratins. CONCLUSIONS: The cytologic characteristics of
      canine AS are widely heterogeneous, but supplementary findings can provide clues
      that are useful for making a cytologic diagnosis. Histologic and
      immunohistochemical confirmation is nonetheless warranted in all cases.

PMID- 15732015
TI  - Correlation of serum alkaline phosphatase activity with the healing process of
      long bone fractures in dogs.
AB  - BACKGROUND: Bone healing is monitored mainly by physical and serial radiologic
      examinations of the fracture site. However, it is sometimes difficult to
      distinguish a delayed union from a nonunion, and advanced imaging techniques may
      not be available. Serum biochemical markers of bone formation, such as alkaline
      phosphatase (ALP) activity, may be clinically useful in evaluating the progress
      of healing. OBJECTIVE: The purpose of this study was to correlate serial values
      of serum ALP activity with the process of fracture healing in dogs and to assess
      its potential as a postsurgical prognostic indicator. METHODS: Changes in serum
      ALP activity were studied in 83 dogs with closed long bone diaphyseal fractures
      treated surgically. Physical and radiologic examinations of the fracture site and
      determination of serum ALP activity and calcium (Ca) and phosphate (P)
      concentrations were performed on admission (day 0); postoperatively on days 10,
      20, and 30; and subsequently on a monthly basis until bone union was completed or
      signs of nonunion were evident. The dogs were allocated into 3 groups with
      respect to the fracture healing progress as documented by physical and serial
      radiologic examination. RESULTS: Group A dogs (n=35) developed a medium-sized
      callus that led to bone union within 2 months. Group B dogs (n=36) had a
      hypertrophic callus and delayed union, within 3-5 months. Group C dogs (n=12) had
      slow progress in fracture healing, with minimal callus formation during a 2-month
      period. Changes in mean serum ALP activity followed the same pattern in groups A
      and B, reaching a maximum level on day 10. Group A values returned to normal
      within 2 months, at which point bone union was complete, whereas group B values
      remained increased and returned to normal within 3-5 months, thus correlating
      with delayed union. In Group C, mean serum ALP activities showed no significant
      changes during the 2-month follow-up period, consistent with failure of bone
      union (nonunion). Serum P and Ca changes followed a proportional and inverse
      pattern to ALP changes, respectively. CONCLUSION: Serial determination of serum
      ALP activity during fracture healing could be an additional tool in predicting
      fractures at risk of developing a nonunion, helping the clinician to choose the
      appropriate intervention.

PMID- 15732016
TI  - Validation and diagnostic efficacy of a lipase assay using the substrate 1,2-o
      dilauryl-rac-glycero glutaric acid-(6' methyl resorufin)-ester for the diagnosis
      of acute pancreatitis in dogs.
AB  - BACKGROUND: Increased serum lipase activity has been used historically to support
      the diagnosis of acute pancreatitis, a common disease in dogs. Most of the lipase
      assays that are currently in use lack optimum sensitivity and specificity.
      OBJECTIVE: The objectives of this study were to 1) validate the 1,2-o-dilauryl
      rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) assay for
      determination of lipase activity in canine serum and 2) compare results,
      reference intervals, sensitivity, and specificity of the DGGR assay with a
      standard 1,2-diglyceride (1,2 DiG) assay for diagnosing acute pancreatitis in
      dogs. METHODS: Precision, linearity, and interference studies were performed for
      method validation on a Hitachi 911 analyzer. Lipase results from the DGGR and 1,2
      DiG assays were compared by linear regression analysis. Sensitivity, specificity,
      and diagnostic efficacy were determined for both assays on a population of 30
      dogs, 15 of which had acute pancreatitis based on history, clinical signs, and
      ultrasound findings. RESULTS: Within-run and within-day coefficients of variation
      (CVs) were low (<3%), with higher day-to-day CVs (< or =14 %). The assay was
      linear between 8 and 2792 U/L. No significant interference by hemolysis and
      lipemia was found. Poor correlation was found between the assays (r(s)=0.84). The
      lipase reference interval was 8-120 U/L for the DGGR assay and 30-699 U/L for the
      1,2 DiG assay. Sensitivity and specificity for the diagnosis of pancreatitis were
      93% and 53%, respectively, for the DGGR assay and 60% and 73% for the 1,2 DiG
      assay. Receiver operating characteristic curve analysis showed similar areas
      under the curve. CONCLUSIONS: On the basis of this study, the DGGR method is
      considered adequate for assaying serum lipase activity in dogs. The high
      sensitivity of the DGGR assay suggests it may be a useful screening test for
      canine pancreatitis.

PMID- 15732017
TI  - Prevalence of Ehrlichia canis infection in thrombocytopenic dogs from Rio de
      Janeiro, Brazil.
AB  - BACKGROUND: Infection with Ehrlichia canis causes a highly variable,
      multisystemic disease in dogs. Nevertheless, many clinicians in Rio de Janeiro,
      Brazil, use the presence of only thrombocytopenia to make a presumptive diagnosis
      of E canis infection. OBJECTIVE: The objective of this study was to determine the
      prevalence of E canis in thrombocytopenic dogs from Rio de Janeiro, Brazil, using
      polymerase chain reaction (PCR). METHODS: Following DNA extraction of whole blood
      samples from 226 dogs, PCR assays were done using primers for rickettsial DNA
      (including Ehrlichia spp, Anaplasma platys and A phagocytophilum) and using E
      canis-specific primers (16S rRNA gene). Dogs were grouped as thrombocytopenic and
      nonthrombocytopenic based on platelet counts. The null hypothesis that there was
      no difference in the prevalence of E canis in these groups was rejected at P<.05.
      RESULTS: Thirty-six (32.1%) of the thrombocytopenic dogs and 4 (3.5%) of the
      nonthrombocytopenic dogs were positive for rickettsial gene sequences (P<.0001).
      Further, 30 (26.8%) of thrombocytopenic dogs and 4 (3.5%) nonthrombocytopenic
      dogs were positive for E canis-specific gene sequences (P<.0001). CONCLUSIONS:
      Although the prevalence of E canis infection was higher in thrombocytopenic dogs,
      less than one third of these dogs had demonstrable E canis infection. Thus,
      thrombocytopenia is not specific for the detection of E canis infection and
      should not be used solely to establish a diagnosis of canine ehrlichiosis, even
      in a geographic area with relatively high disease prevalence.

PMID- 15732019
TI  - Acute megakaryoblastic leukemia with erythrophagocytosis and thrombosis in a dog.
AB  - A 7-year-old, intact male Dachshund was presented to the Lyon veterinary school
      for lethargy and anorexia of several weeks duration. The main clinical signs were
      pale and icteric mucous membranes, hepatomegaly, splenomegaly, and
      lymphadenopathy. Results of a CBC and plasma biochemistry tests revealed severe
      nonregenerative anemia, thrombocytopenia, and increased alanine aminotransferase
      and alkaline phosphatase activities. Blood smear evaluation and cytologic
      examination of lymph node and bone marrow aspirate specimens revealed a large
      population of poorly differentiated blast cells with morphologic features
      suggesting megakaryocytic lineage. A low number of well-differentiated but
      dysplastic megakaryocytes also were observed in lymph node and bone marrow
      smears. A few blast cells were erythrophagocytic. Blast cells were positive for
      glycoprotein IIIa, factor VIII-related antigen, and factor XIII using
      immunocytochemistry. The dog was euthanized and necropsied. Histologic findings
      consisted of diffuse, massive infiltration of lymph nodes, liver, and spleen by
      megakaryoblasts and atypical megakaryocytes, with widespread thrombosis. This
      case confirms the usefulness of immunochemistry, including for factor XIII, in
      the diagnosis of megakaryoblastic leukemia, and demonstrates the unique features
      of tumor cell erythrophagocytosis and marked fibrinous thrombosis, which have not
      been reported previously in dogs.

PMID- 15732018
TI  - Effect of intestinal inflammation on fecal elastase concentration in dogs.
AB  - BACKGROUND: A commercially available ELISA kit for fecal elastase measurement can
      be used in the diagnosis of exocrine pancreatic insufficiency (EPI) in dogs.
      However, other causes of diarrhea also may affect fecal elastase concentration.
      OBJECTIVE: This study was undertaken to determine whether intestinal inflammation
      alters fecal elastase concentration in dogs. METHODS: Fecal elastase
      concentration was measured with an ELISA kit in the following groups of dogs:
      group 1 (n=16), control dogs, without gastrointestinal disease; group 2 (n=14),
      dogs with diarrhea and no histopathologic evidence of intestinal inflammation;
      and group 3 (n=12), dogs with diarrhea and histopathologic evidence of intestinal
      inflammation. Serum trypsin-like immunoreactivity (TLI) was determined in dogs
      with diarrhea to rule out EPI. RESULTS: All dogs in groups 2 and 3 had serum TLI
      concentrations >5 microg/L, ruling out EPI. No statistically significant
      difference was found in fecal elastase concentration among the 3 groups of dogs
      (P=.969). CONCLUSIONS: The results indicate that intestinal inflammation does not
      affect fecal elastase concentration, such that test results may be used to
      exclude a diagnosis of EPI even in animals with inflammatory bowel disease.

PMID- 15732020
TI  - Cytologic diagnosis of Lawsonia intracellularis proliferative ileitis in a
      Japanese snow macaque (Macaca fuscata).
AB  - Diffuse ileal thickening and ileocecocolic lymphadenomegaly were observed during
      exploratory laparotomy in a 2-year-old male Japanese snow macaque (Macaca
      fuscata) that had flu-like signs and diarrhea. Cytologic examination of ileal
      biopsy imprints revealed many mature, mildly karyolytic neutrophils and fewer
      well-differentiated lymphocytes, eosinophils, macrophages, and plasma cells in a
      background containing amorphous, necrotic material. Tightly cohesive sheets of
      moderately pleomorphic epithelial cells also were seen. The cytologic diagnosis
      was chronic, active, mixed inflammation with atypical epithelial cells and
      necrosis. Histologically, the mucosal and crypt epithelium was moderately
      hyperplastic with a loss of goblet cells, increased mitoses, and frequent crypt
      abscesses. Within the lamina propria and extending into the submucosa was a
      marked neutrophilic infiltrate, with low numbers of lymphocytes, histiocytes,
      plasma cells, and eosinophils. The histologic diagnosis was chronic, diffuse,
      marked suppurative and lymphocytic ileitis. Warthin-Starry silver staining of the
      ileal biopsy and imprint specimens demonstrated numerous pleomorphic, curved
      bacilli consistent with Lawsonia intracellularis. Polymerase chain reaction (PCR)
      and immunohistochemistry confirmed the identity of the infectious agent. L
      intracellularis infection may be underdiagnosed because silver stain is required
      to visualize the organism with light microscopy and because the pathognomonic
      crypt hyperplasia may be complicated by secondary pathologic changes. Application
      of silver stain to cytologic specimens should be considered when distal
      intestinal lesions associated with hyperplastic epithelium, with or without
      inflammation, hemorrhage, or necrosis, are identified in animals with clinical
      signs of enteritis, especially in frequently affected species or in stressed or
      young animals.

PMID- 15732021
TI  - Carcinoma of the submandibular salivary glands with multiple metastases in a cat.
AB  - A 9-year-old neutered male domestic shorthair cat was presented because of
      coughing, dysphagia, and prostration. Examination revealed firm bilateral
      anterocervical swellings extensively adhered to the surrounding tissues.
      Anisocoria with left-side miosis was also evident. X-ray and ultrasound
      examinations along with a fine-needle aspiration biopsy were performed. Slides
      were stained with May-Grunwald Giemsa, and a diagnosis of salivary gland
      carcinoma was made. At surgery, the tumor was found to involve both submandibular
      salivary glands as well as adjacent lymph nodes and surrounding tissues. The cat
      was euthanized and necropsy was performed. The majority of tissues and organs
      examined histologically, including mandibular and retropharyngeal lymph nodes,
      soft palate, laryngopharynx and lungs, contained neoplastic cells whose
      appearance was consistent with adenocarcinoma. Bilateral salivary adenocarcinoma
      has not previously been reported in cats, and extensive metastases are rare.

PMID- 15732022
TI  - Draining skin lesion from a desert poodle.
AB  - A 16-month-old intact female Poodle in Arizona had a history of intermittent
      coughing of a few weeks duration. Coccidiomycosis antibody screening test results
      were negative for immunoglobulin (Ig) M, but were positive (1:64) for IgG. Fine
      needle aspiration specimens of a draining lesion on the right palmar front foot
      contained large numbers of neutrophils, many of which contained bacteria, and
      lower numbers of macrophages. A few small structures also were observed, 2-5
      microm in diameter with thin, nonstaining capsules and small, round to oval
      densely aggregated, eccentric nuclei. Cytologic findings were consistent with
      septic pyogranulomatous inflammation with Coccidiodes immitis endospores. Fungal
      culture of a sample from the draining lesion yielded white growth with barrel
      shaped arthroconidia. Identification of the organism as C immitis was confirmed
      by a commercial DNA probe test. Although coccidioidomycosis often is diagnosed by
      microscopic identification of C immitis spherules in cytologic specimens, in this
      case only endospores, which are released from mature spherules, were observed. In
      cases of suspected coccidiodomycosis, the unique morphology of endospores may be
      useful in making a cytologic diagnosis.

PMID- 15732023
TI  - Tail-base mass from a "horse of a different color".
AB  - A 14-year-old bay Thoroughbred gelding was presented for evaluation of a mass at
      the base of the tail. The mass had been present for 1 year, and recently had
      begun to increase in size. Additional masses were found around the eye and
      shoulder. A fine-needle aspirate of the tail-base mass revealed highly anaplastic
      round to polyhedral cells containing dark green to black cytoplasmic granules
      interpreted to be melanin. Histologically, the mass was composed of pleomorphic,
      poorly pigmented, round to polyhedral cells interpreted to be neoplastic
      melanocytes. With immunohistochemistry, the cells were positive for vimentin and
      S-100, but negative for pancytokeratin and Melan-A. The cytologic and
      histopathologic diagnoses were amelanotic melanoma. The horse was treated with
      cimetidine, but the tumor continued to progress. In this report, we describe the
      cytopathologic features of an aggressive amelanotic melanoma in a non-grey horse
      and emphasize the unique correlation between cytologic and histologic findings.

PMID- 15732024
TI  - True grit: the tale of a subcutaneous mass in a dog.
AB  - A 14-month-old, intact, male German Shepherd dog was referred for a 6 x 3-cm,
      firm mass in the left pelvic limb. Fine needle aspiration yielded chalky white
      material. May-Grunwald-Giemsa-stained smears showed a uniform background of
      amorphous, poorly stained, light-blue material and scattered foamy macrophages, a
      few naked nuclei, and cellular debris. The cytologic diagnosis of calcinosis
      circumscripta was confirmed by histologic evaluation of the surgically removed
      mass. In this report, we document the unique cytologic and histologic patterns of
      this uncommon tumor-like lesion.

PMID- 15732025
TI  - The effect of gender on outcome in digitalis-treated heart failure patients.
AB  - BACKGROUND: The use of digitalis is recommended for the treatment of heart
      failure to reduce hospitalization. Recent data suggest that digitalis treatment
      may adversely affect survival in women but not in men. We studied patients with
      left ventricular dysfunction enrolled in the Studies of Left Ventricular
      Dysfunction (SOLVD) to determine whether there was a gender-based survival
      difference in patients treated with digitalis. METHODS AND RESULTS: Symptomatic
      (n = 2569) and asymptomatic (n = 4228) patients with left ventricular ejection
      fraction < or = 0.35 were studied. Digitalis use was assessed at baseline and
      baseline demographic variables were catalogued and compared. A multivariate
      analysis, incorporating known covariates of risk for adverse cardiovascular
      events, was used to examine the association of digitalis with all-cause
      mortality, cardiovascular death, death from heart failure, and arrhythmic death,
      with, or without, worsening heart failure in women compared with men. Analysis
      for an interaction between digitalis and gender on mortality was also performed.
      No interaction between gender and digitalis treatment on survival was found, and
      there was no significant difference in the hazard ratios for men and women on
      digitalis either with respect to all-cause mortality, cardiovascular mortality,
      heart failure mortality, or arrhythmic death with worsening heart failure. When
      mortality for arrhythmic death without worsening heart failure was adjusted for
      the probability of being treated with digitalis (propensity analysis), women
      fared better than men. CONCLUSION: Data from the SOLVD trials suggest that
      digitalis treatment of heart failure does not result in a difference in survival
      between men and women. Because a randomized trial to definitively answer the
      question is unlikely, and perhaps inappropriate, examination of other heart
      failure populations for a gender-digitalis interaction is indicated.

PMID- 15732026
TI  - Was it digoxin toxicity?...very likely.

PMID- 15732027
TI  - Anemia in patients with heart failure: prevalence and prognostic role in a
      controlled trial and in clinical practice.
AB  - BACKGROUND: Aims of the present study were (1) to confirm the prognostic role of
      anemia in patients with heart failure (HF) and (2) to analyze this aspect in
      relatively unselected patients with HF monitored prospectively in a community
      setting (IN-CHF), and in patients selected for enrollment into the Valsartan
      Heart Failure Trial (Val-HeFT). METHODS AND RESULTS: In both Val-HeFT and IN-CHF
      Registry, anemia was defined as a hemoglobin (Hb) level < or = 11 g/dL in women
      and < or = 12 g/dL in men. Of the 2411 patients of the IN-CHF Registry, 15.5% had
      anemia, whereas in the 5010 patients of the Val-HeFT trial, the prevalence was
      9.9%. In the IN-CHF registry, 1-year all-cause mortality was significantly higher
      in anemic patients (25.9%) than in patients without anemia (13.2%) (P < .0001).
      The association of anemia with mortality was confirmed by the multivariable
      analysis (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.20-1.97). The
      risk of death decreased by 9.7% for each gram of Hb. The Val-HeFT trial showed an
      all-cause mortality rate for anemic patients of 29.6% over a mean follow-up
      period of 22.4 months versus 18.5% (P < .0001) in patients without anemia. After
      adjustment, anemia retained its negative independent prognostic role (HR 1.26,
      95% CI 1.04-1.52). When Hb was considered as a continuous variable, the risk of
      death decreased by 7.8% for each gram of Hb. CONCLUSIONS: Anemia was confirmed to
      be an independent negative prognostic factor in patients with HF. This finding is
      consistent in 2 different clinical contexts, a controlled trial and a registry in
      clinical practice, in which patient characteristics and outcome are largely
      different.

PMID- 15732028
TI  - Anemia and new-onset congestive heart failure in the general Medicare population.
AB  - BACKGROUND: Anemia is associated with disease severity and prognosis for patients
      with congestive heart failure (CHF). It is unknown whether anemia is associated
      with the development of new-onset CHF in the elderly. METHODS AND RESULTS: This
      retrospective longitudinal cohort study used the Medicare 5% database. In the
      incident analysis, the study sample comprised subjects without CHF in 1999 (n =
      1,063,495); the main exposure variable evaluated was the presence or absence of
      anemia in 1999; and the primary study outcome was the occurrence of new-onset
      CHF. The prevalence of chronic anemia and CHF in 1999 was 5.0% and 9.9%,
      respectively. The incidence of new-onset CHF in 2000 in those with and those
      without anemia in 1999 was 12.3% and 5.9%, respectively, corresponding to an
      adjusted hazard ratio of 1.29 ( P < .001), a value intermediate between the
      hazard ratios of 1.13 ( P < .001), and 1.76 ( P < .001) associated with
      hypertension and atherosclerotic heart disease, respectively. Anemia also was
      associated with death in the year after new-onset CHF (adjusted hazard ratio,
      1.28; P < .001). CONCLUSION: Anemia in the Medicare population is associated with
      the diagnosis and prognosis of new-onset CHF.

PMID- 15732029
TI  - Managed care patients with heart failure: spectrum of ventricular dysfunction and
      predictors of medication utilization.
AB  - BACKGROUND: Heart failure (HF) is a common clinical syndrome resulting in high
      morbidity and mortality. We examined the spectrum of ventricular dysfunction, and
      investigated the predictors of angiotensin-converting enzyme (ACE) inhibitor,
      beta-blocker, and spironolactone prescription in 1613 managed care patients with
      HF. METHODS AND RESULTS: The diagnosis of HF was made by a HF discharge diagnosis
      or at least 3 physician encounters with a HF diagnosis during 2000. Logistic
      regression was used to identify predictors of medication prescription. Preserved
      systolic function was documented in 37%, moderate-severe systolic dysfunction in
      31%, mild systolic in 14%, and 18% had inadequate documentation. The mean age was
      69 years, 58% were women, 24% African American, and 60% were Medicare patients.
      Patients without HF type documented were the least aggressively treated. Coronary
      artery disease, hypertension, and diabetes predicted increased utilization of ACE
      inhibitor and beta-blocker therapies. History of nephropathy was associated with
      less ACE inhibitor prescription. Advancing age predicted less utilization of beta
      blockers and spironolactone. Neither ethnicity nor gender influenced medication
      prescription. CONCLUSION: Preserved left ventricular function was common.
      Documentation of significant systolic dysfunction was associated with improved
      quality of care. Interventions to encourage documentation of HF type and further
      study of HF with preserved systolic function are warranted.

PMID- 15732030
TI  - Beta-blockers and inspiratory pulmonary function in chronic heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) patients complain of breathlessness and
      fatigue. Respiratory muscle function is impaired in CHF patients and may
      contribute to their symptoms. Beta-blockers cause fatigue but have become part of
      the standard management of CHF. We explored the relation between respiratory
      muscle power in CHF and the effects of long-term beta-blockade. METHODS AND
      RESULTS: A total of 52 CHF patients and 25 control subjects underwent
      echocardiography, peak exercise testing with metabolic gas exchange analysis, and
      measurement of forced vital capacity (FVC), forced expiratory volume in 1 second
      (FEV1), peak inspiratory flow (PIF), and forced inspiratory volume in 1 second
      (FIV1). Of the patients, 35 started beta-blocker therapy and were tested again at
      1 year. Patients had lower peak oxygen consumption (pV(O2) (19.3 [4.5] versus
      37.3 [8.4] mL/kg/min, P < .0001), exercise time (414 [134] versus 817 [193]
      seconds, P < .0001), and anaerobic threshold (13.8 [3.8] versus 27.2 [8.2]
      mL/kg/min, P < .0001). Patients also had a steeper relationship between
      ventilation (V(E)) and carbon dioxide (CO2 ) (V(E)/V(CO2)) (40.0 [6.8] versus
      26.4 [2.0], P < .0001); lower FEV1, FVC, and FIV1 (89 [15] versus 111 [24]%
      expected, P < .0001, 80 [20] versus 94 [21]% expected, P < .001 and 2.5 [1.6]
      versus 3.0 (0.9) L, P < .02); and there was a correlation between pV(O2) and FIV1
      (r = 0.24, P < .05) for the patients. The slope relating symptoms of
      breathlessness (Borg score) to ventilation (Borg/V(E) slope) also correlated with
      FIV1 (r = 0.36, P < .02). Beta-blocker therapy improved echocardiographic
      variables, but not pV(O2). There was no change in PIF or FIV1. There was a
      significant reduction in FEV 1 after beta-blocker treatment (P < .01).
      CONCLUSION: Inspiratory flows are impaired in patients with chronic heart failure
      and correlate with the degree of functional impairment. This may be due to a
      combination of respiratory muscle weakness and reduced lung compliance. The
      reduction in inspiratory capacity is not influenced by long-term beta-blockade.

PMID- 15732031
TI  - Relationship between oxidative stress and systolic dysfunction in patients with
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Progression of hypertrophic cardiomyopathy (HCM) to left ventricular
      dilatation and systolic dysfunction sometimes occurs. However, the mechanism is
      not known. We examined whether oxidative stress was elevated in myocardia of HCM
      patients and whether the levels were correlated with left ventricular dilatation
      and systolic dysfunction. METHODS AND RESULTS: Endomyocardial biopsy samples
      obtained from the right ventricular side of the septum of 31 patients with HCM,
      and 10 control subjects were studied immunohistochemically for the expression of
      4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation
      product. Expression of HNE-modified protein was found in all myocardial biopsy
      samples from patients with HCM. Expression was distinct in the cytosol of
      cardiomyocytes. The expression levels in patients with HCM were significantly
      increased compared with those in control subjects (P = .0005). The expression
      levels in patients with HCM were correlated with left ventricular end-diastolic
      diameter (r = 0.483, P = .0053) and end-systolic diameter (r = 0.500, P = .0037)
      determined by echocardiography. The expression levels were inversely correlated
      with left ventricular ejection fraction determined by left ventriculography (r = 
      0.640, P = .0001). CONCLUSION: Oxidative stress was elevated in myocardia of HCM
      patients and the levels were correlated with left ventricular dilatation and
      systolic dysfunction. Oxidative stress is involved in the pathogenesis of heart
      failure in patients with HCM.

PMID- 15732032
TI  - Plasma monitoring of the myocardial specific tissue inhibitor of
      metalloproteinase-4 after alcohol septal ablation in hypertrophic obstructive
      cardiomyopathy.
AB  - BACKGROUND: The overall goal of this study was to develop an assay procedure for
      measuring the relative abundance of tissue inhibitor of metalloproteinase (TIMP)
      4 in plasma, and then use this approach to determine dynamic changes of TIMP-4
      levels in hypertrophic obstructive cardiomyopathic (HOCM) patients after an acute
      myocardial infarction (MI). Matrix metalloproteinases (MMPs) contribute to tissue
      remodeling and are regulated by the endogenous TIMPs. TIMP-4 is observed to be
      expressed in higher abundance in the myocardium when compared with other types of
      tissues. Recent clinical studies have measured changes in TIMP-4 levels; however,
      these studies have been limited to measuring this protein from myocardial tissue
      samples. To date, no studies have monitored TIMP-4 levels in plasma samples.
      METHODS AND RESULTS: Plasma TIMP-4 levels were examined (by semiquantitative
      immunoblotting) in normal (n=18) and HOCM (n=16) patients after alcohol-induced
      MI. Serial measurements of plasma TIMP-4 levels were examined up to 60 hours
      after alcohol-induced MI in patients with HOCM. Unglycosylated plasma TIMP-4
      levels increased 250% in the HOCM patients when compared with normal controls.
      Total plasma TIMP-4 levels decreased by 20% at 30 hours after alcohol-induced MI.
      CONCLUSIONS: The unique results demonstrated that an induction of a controlled
      MI, specifically through alcohol ablation, caused a reduction in plasma TIMP-4
      levels in HOCM patients after alcohol-induced MI that would facilitate myocardial
      remodeling in the early post-MI setting.

PMID- 15732033
TI  - Reversal of left ventricular remodeling by pericardial tamponade.

PMID- 15732034
TI  - Cardiac tamponade, myocardial stress, and reverse remodeling.

PMID- 15732035
TI  - Advancing immunosuppression therapy to counter the progression of cardiac
      allograft vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the major cause of late
      mortality in heart transplant recipients. Because immunosuppressive therapy has
      been convincingly shown to suppress cellular rejection and prolong cardiac
      allograft survival, we assessed the efficacy of advancing immunosuppressive
      therapy in reversing or delaying CAV by switching azathioprine to combination
      mycophenolate mofetil and prednisone (MMF-P). METHODS AND RESULTS: Seventeen
      adult posttransplant patients, whose CAV was prospectively approached with the
      MMF-P protocol, were studied. The development of significant CAV was declared on
      the index coronary angiogram and the MMF-P protocol was instituted. The degree of
      occlusion for all coronary lesions was quantitated for the index angiogram, and
      for the angiograms performed 1 year before (baseline) the index angiogram and
      annually for 2 years after the index angiogram (MMF-P years 1 and 2). There was a
      significant change in percent occlusion over time (P < .001). Percent occlusion
      increased significantly from the baseline year to the index CAV year, but then
      decreased significantly from the index CAV year to the MMF-P treatment years 1
      and 2. CONCLUSION: Advancing immunosuppression with MMF-P can delay the
      progression of and partially reverse lumen narrowing of CAV in heart transplant
      recipients.

PMID- 15732036
TI  - Partial support with a centrifugal left ventricular assist device reduces
      myocardial oxygen consumption in chronic, ischemic heart failure.
AB  - BACKGROUND: Left ventricular assist devices (LVAD) are increasingly used for
      heart failure (CHF); however, the level of optimal support has not been
      elucidated. We hypothesize that partial LVAD support in an ovine model of
      microinfarction-induced CHF significantly reduces left ventricular myocardial
      oxygen consumption (LVVO2). METHODS AND RESULTS: Microembolization of the
      circumflex coronary artery was used to induce CHF in 5 sheep (ejection fraction
      28 +/- 2%). Four months later, animals underwent implantation of a centrifugal
      LVAD. LVAD flow was incrementally increased from 0% (baseline) to 25%, 50%, and
      75% support of the LV. LVVO2 and stroke work (SW) were calculated at each
      increment. At baseline, LVVO2 (microL/100 g LV/beat) measured 43.2 +/- 3.4. LVVO2
      decreased to 26.5 +/- 8.2,* 20.3 +/- 8.9,* and 12.6 +/- 6.3* at 25%, 50%, and 75%
      support (*P < .05). SW (mm Hg/mL) measured 1933.0 +/- 275.7 at baseline and
      decreased to 1588.0 +/- 204.1, 1181.0 +/- 157.2,* and 764.5 +/- 171.7* at 25%,
      50%, and 75% support. Cardiac output, heart rate, and left main coronary artery
      blood flow were unaffected with partial support. CONCLUSION: Complete support
      with a centrifugal LVAD is not necessary for achieving significant reductions in
      LVVO2 . Partial support of as little as 25% significantly reduces LVVO2 in CHF
      through comparatively minor reductions in cardiac work. This is the first study
      to examine partial LVAD support in a CHF model.

PMID- 15732037
TI  - Carvedilol modulates the expression of hypoxia-inducible factor-1alpha and
      vascular endothelial growth factor in a rat model of volume-overload heart
      failure.
AB  - BACKGROUND: The use of beta-blockers has emerged as a beneficial treatment for
      congestive heart failure. Hypoxia-inducible factor-1alpha (HIF-1alpha) is tightly
      regulated in the ventricular myocardium. However, the expression of HIF-1alpha in
      chronic heart failure resulting from volume overload and after treatment with
      beta-blocker is little known. METHODS AND RESULTS: To test the hypothesis that
      HIF-1alpha plays a role in the failing myocardium because of volume overload, an
      aorta-caval shunt was created for 4 weeks in adult Sprague-Dawley rats to induce
      volume-overload heart failure. Carvedilol at 50 mg/kg body weight per day after
      surgery was given. The heart weight and body weight ratio increased from 2.6 +/-
      0.3 in the sham group to 3.9 +/- 0.7 (P < .001) in the shunt group. Left
      ventricular end-diastolic dimension increased from 6.5 +/- 0.5 mm to 8.7 +/- 0.6
      mm (P < .001). Treatment with carvedilol in the shunt group reversed the heart
      weight and ventricular dimension to the baseline values. Western blot showed that
      HIF-1alpha, vascular endothelial growth factor (VEGF), and brain natriuretic
      peptide (BNP) proteins were upregulated and nerve growth factor-beta (NGF-beta)
      downregulated in the shunt group. Real-time polymerase chain reaction showed that
      mRNA of HIF-1alpha, VEGF, and BNP increased and mRNA of NGF-beta decreased in the
      shunt group. Treatment with carvedilol reversed both protein and mRNA of HIF
      1alpha, VEGF, BNP, and NGF-beta to the baseline values. Increased
      immunohistochemical labeling of HIF-1alpha, VEGF, and BNP in the ventricular
      myocardium was observed in the shunt group and carvedilol again normalized the
      labeling. CONCLUSION: HIF-1alpha and VEGF mRNA and protein expression were
      upregulated in the rat model of volume-overload heart failure. Treatment with
      carvedilol is associated with a reversal of abnormal regulation of HIF-1alpha and
      VEGF in the failing ventricular myocardium.

PMID- 15732039
TI  - [Survival of the renal transplant: data from international registries].
AB  - In this article the authors examine which factors have the greatest influence on
      both renal survival and renal function by reviewing the database of the main
      International Registries. Both patient and renal survival rates have been
      continuously improving over recent years. In the case of a living donor, graft
      survival is similar either for related or unrelated donor. Long-lasting
      hypertension and low donor glomerular filtration rate are relevant factors
      negatively affecting the outcome. Older recipients have poorer prognosis. Graft
      loss due to the recurrence of the original disease actually has a higher
      incidence. Delayed graft function and acute rejection are the major determinants
      of poor prognosis. In recent studies, one year renal function proved to be the
      best predictor of poor outcome. Several other factors, such as recipient
      hypertension, dyslipidemia, smoking and recipient compliance influence graft
      survival.

PMID- 15732040
TI  - [Clinicopathologic correlations in acute renal graft rejection].
AB  - Although the diagnostic and therapeutic outcome of renal transplantation has
      successfully improved during the last decades, acute graft rejection (AGR) is
      still an ongoing cause of concern being often associated with irreversible graft
      dysfunction. Renal biopsy remains a valuable tool in the initial assessment of
      the potential graft malfunction especially during the early post-transplant
      period. It is an accurate and sensitive means for detecting prognostically
      relevant microscopic abnormalities, and assisting in subsequent patient
      management. For long time, the histopathologic evaluation of AGR has suffered
      from an irreducible bias with poor interobserver rates. Nowadays, the
      classification schemes of AGR include the BANFF approach and the National
      Institute of Heath Collaborative Clinical Trials in Transplantation (NIH-CCTT)
      system: both have been originally designed in order to improve the diagnostic
      reproducibility of AGR among pathologists. Arteritis and tubulitis, along to
      clinical information, constitute the cardinal features of the BANFF
      classification. Distinguishing features of the traditional NIH-CCTT system
      includes microscopic criteria such as assessment of interstitial hemorrhage,
      extent and quality of inflammatory infiltrate, and acute glomerulitis, in
      addition to tubulitis and arteritis. The BANFF classification has apparently
      gained more popularity than the time-honored NIH-CCTT system since, if used in
      the appropriate clinical context, it allows a more accurate assessment of AGR,
      provides prognostically relevant information, and has a better reproducibility
      rate among pathologists. Nevertheless, the accuracy trend has not significantly
      improved during the last few years.

PMID- 15732041
TI  - [Functional loss of the transplanted kidney: immunological and non-immunological
      factors].
AB  - During the past few years, the short-term graft survival after kidney
      transplantation has improved dramatically, a phenomenon not paralleled by an
      increase in the long-term graft survival. This is due to the progressive renal
      injury and dysfunction known as chronic transplant nephropathy or 'chronic
      rejection', a process that involves both immune and non-immune factors.
      Immunological factors include T- and B-cell recognition of alloantigens,
      cytomegalovirus infection, and endothelial cell activation followed by vascular
      smooth cells proliferation. Among nonimmune mechanisms, proteinuria and
      hypertension play a relevant role. Moreover, the reduced number of functioning
      nephrons may trigger an inflammatory process that, eventually, contributes to the
      loss of the graft. Several studies have documented the efficacy of blocking the
      renin-angiotensin system (RAS) in reducing proteinuria and preventing renal
      function deterioration in experimental models of chronic rejection. Early results
      are promising. However, available clinical trials are rather limited in terms of
      number of patients enrolled, consequently they cannot be considered definitive.
      Since several pathogenetic factors are involved in the progression of chronic
      transplant nephropathy, a multidrug approach with specific immunosuppressants and
      RAS-blocking drugs has been proposed to control/prevent chronic injury and
      progressive renal deterioration. Preliminary results in experimental models are
      promising. Data from prospective clinical trials are, however, mandatory to
      confirm the efficacy of a polypharmacological strategy in preventing chronic
      rejection.

PMID- 15732042
TI  - [Clinical results of the various replacement therapies for chronic renal failure:
      haemodialysis and renal transplantation].
AB  - Results from recent studies have demonstrated that kidney-transplanted patients
      have better expectation and quality of life than dialysis patients on a waiting
      list for kidney transplant. Moreover, the scientific literature has conclusively
      shown that the survival of the patient and of the kidney graft are better in
      patients who received a kidney from a living donor, than in patients who received
      a cadaveric kidney. The main factors that may have a negative influence on the
      kidney transplant are: the recipient's age, diabetes mellitus, smoking and the
      time spent on dialysis before the transplant. The shortage of cadaveric kidneys
      and the small number of living kidney transplant are the main obstacles to a more
      widespread use of kidney transplantation. Kidney transplant from living donors
      needs to be implemented because it represents the best treatment for patients
      with kidney failure and it can decrease or even avoid the need for dialysis
      before kidney transplantation.

PMID- 15732043
TI  - [Clinical anatomical features of chronic dysfunction in the transplanted kidney].
AB  - Histopathological features of transplanted kidneys which gradually lose graft
      function have been traditionally reported with the term of chronic rejection
      (CR). In 1997 Banff's classification indicated the adoption of a new term for all
      these histological features, namely Chronic allograft nephropathy (CAN),
      recommending that the presence of morphological aspects suggestive of chronic
      rejection, such as chronic transplant glomerulopathy (CTG) and proliferative
      endoarteritis (PE), has to be specified. On the basis of these criteria we
      reviewed the renal biopsies of 92 patients who underwent kidney transplantation
      from 1999 to 2002. In all cases the biopsy had been performed 6 months after
      organ transplantation. In 30 of the 92 patients CTG and/or PE was evident
      supporting a diagnosis of CR; on the contrary, in 11 of the 92 patients the final
      diagnosis based on histological evidence was that of CAN. Clinical and laboratory
      tests revealed that the presence of proteinuria in patients with CR at the time
      of diagnosis was the single statistically significant difference between these
      two groups. In 7 of the 32 patients where the diagnosis of CR was based on the
      presence of early features of CTG, the treatment with ACE-I induced complete
      remission of the proteinuria. Cyclosporine-induced arteriolopathy (CSA)
      represents an additional histological finding which has been associated with
      graft loss in the transplanted kidney. The observation of arteriolopathy, similar
      to CSA in patients who did not receive calcineurine inhibitors, suggests some
      caution in the use of this diagnostic criteria.

PMID- 15732044
TI  - [Recurrent and de novo glomerular disease after renal transplantation].
AB  - The development and progression or recurrent and de novo renal disease does not
      seem to have been influenced by the use of newer immunosuppressive agents. The
      rate of development of recurrent and de novo renal disease has been variable and
      is perhaps related to pre-existing immunological and/or haematological factors.
      The diagnosis of recurrent glomerulonephritis requires an accurate diagnosis of
      both primary renal disease and subsequent disease in the transplant kidney.
      Published data suggest that recurrent glomerulonephritis occurs in 6 to 19.4% of
      all renal transplant recipients, and causes the loss of 1.1 to 4.4% of all renal
      allografts. However, the propensity for glomerulonephritis to recur seems to be
      time dependent. Consequently, as grafts survival increases, so, too, does the
      likelihood of disease recurrence. In conclusion, currently available data on
      recurrence patterns of the less common nephropathies are unfortunately inadequate
      and our practice is therefore guided by small series, case reports, and local
      experience. It is to be hoped for that this deficit be addressed in the near
      future through the use of powerful database and registries, some of which are
      prospectively collecting data on specific disorders. Prospective studies on the
      treatment of recurrent glomerulonephritis are lacking. As grafts last longer and
      recurrent glomerulonephritis becomes a more significant entity, affecting greater
      numbers of patients, the opportunity to study management prospectively will be
      possible. This will probably require a cooperative, multicentre approach but it
      is clearly the only way forward, remembering that renal transplantation is a
      treatment, not a cure.

PMID- 15732045
TI  - [Surgical complications after kidney transplantation].
AB  - Chronic renal failure needs substitutive treatment such as haemodialysis and
      peritoneal dialysis for the patient to survive. Kidney transplantation (KTx)
      improves survival of the patient with chronic renal failure. Since the first KTx,
      performed by Merrill in Boston in 1959, advances in medical therapy,
      immunosuppressive therapy and refinements in surgical technique have improved the
      quality of life of the transplant patient. We present a review of the incidence,
      diagnosis and therapy of surgical complications after KTx reported in the
      literature and a retrospective analysis of 297 consecutive cadaveric donor kidney
      transplants done in our institution from September 1993 to September 2002.
      Vascular complications represent 5-10% of postoperative complications. Our
      experience showed an incidence of 1.7% renal artery thrombosis, 1.4% renal vein
      thrombosis, 1.7% renal artery stenosis, 1.4% arterial rupture due to fungal
      arteritis, 0.7% spontaneous graft ruptures and 12% lymphoceles. Urological
      complications account for 10-15% of postoperative complications. In our series we
      found an incidence of 7.4% urinary leakage, 2.7% urinary obstruction and 3%
      urinary reflux. Gastrointestinal complications represent 16% of postoperative
      complications. Our series showed 1% pancreatitis with an overall mortality of 33%
      and an incidence of 1.7% intestinal perforations. Surgical complications still
      represent a challenge that increments morbidity and mortality among kidney
      transplant recipients. Data shown may offer some guidance on how to deal with
      early and late post-transplant surgical complications.

PMID- 15732046
TI  - [Infectious complications after renal transplantation].
AB  - Infections still represent a major clinical issue in the field of renal
      transplantation, impacting on graft and patient survival. Post-surgical
      complications in the immediate post-transplantation period, and immunosuppression
      (related to the use of new drugs such as mycophenolate mofetil, rapamicin,
      sirolimus and tacrolimus, and of increasingly aggressive immunosuppressive
      regimens) in later phases entail an increased risk for infection. Bacteria (in
      particular Enterobacteriaceae, non-fermenting Gram-negative bacilli and
      Enterococcus spp) and Candida spp are a frequent cause of urinary tract infection
      in the early post-transplantation phase. Cytomegalovirus (CMV) is a frequent
      infectious complication (20-60% of patients) whose risk is enhanced by
      mycophenolate mofetil. It can cause a variety of diseases: organ or disseminated
      acute disease, acute graft rejection, chronic allograft nephropathy, graft
      glomerulopathy, renal artery stenosis, induction of secondary bacterial or
      mycotic disease. Monitoring CMV antigenemia (pp65) allows a strategy based on pre
      emptive therapy among patients with evidence of virological activity. BK virus
      (BKV) is a polyomavirus associated to various clinical syndromes in severely
      immunocompromised patients, such as haemorrhagic cystitis, ureteral stenosis and
      others. The variety and severity of infectious complications in this field
      mandate a multidisciplinary approach involving, next to the nephrologist and the
      surgeon, an infectious disease consultant and a clinical microbiologist.

PMID- 15732047
TI  - [Cardiovascular disease after renal transplantation].
AB  - Cardiovascular disease is the leading cause of morbidity and mortality following
      renal transplantation. Because many renal transplant recipients die with
      functioning grafts, deaths resulting from cardiovascular disease have became an
      increasingly important cause of graft loss, particularly after the first post
      transplantation year. Moreover, a contribution of some cardiovascular risk
      factors to renal allograft dysfunction has been demonstrated. A number of
      observational studies suggest that cardiovascular disease is more common in renal
      transplant patients than in the general population. The excessive risk for
      cardiovascular disease is related to a high prevalence and accumulation of
      atherogenic risk factors before and after transplantation. Hypertension, post
      transplantation diabetes and hyperlipidemia are well-recognized risk factors for
      the development of cardiovascular events after renal transplantation and are
      strongly associated with immunosuppressive therapy. Progressive renal dysfunction
      may also influence the risk of cardiovascular complications after renal
      transplantation. The elevated risk may also be caused by non- traditional risk
      factors such as anaemia, adhesion molecules, hyperhomocysteinemia,
      microinflammatory state, abnormal coagulation and oxidative stress. To prevent
      post-transplantation cardiovascular disease it is crucial to define the
      etiological risk factors. Some risk factors can be modified, and for some of
      these, there is strong evidence from studies in the general population that
      intervention improves survival. Given the significant morbidity and mortality of
      cardiovascular disease in renal transplant recipients, aggressive treatment
      intervention for potentially modifiable factors are strongly advocated after
      transplantation. In addition to treatment intervention, risk management should
      also involve tailoring the immunosuppressive regimen to minimize both direct and
      indirect cardiovascular risks. In this article we attempted to review and
      quantify the post-transplant risk factors for cardiovascular disease as well as
      offer suggestions on optimizing the therapy or treatment strategies to minimize
      the risk of cardiovascular complications in renal transplant patients. Reduction
      of cardiovascular morbidity and mortality can improve not only the life
      expectancy and quality of life of the transplant recipients but also their graft
      function and survival.

PMID- 15732048
TI  - [Cancer after kidney transplantation].
AB  - In our experience, cancer is the second cause of death after renal
      transplantation. In fact, 27% of the deaths we observed at 15-year follow-up were
      due to neoplasm and 30% to cardiovascular disease. Cancer is a late complication
      that becomes more common after the fifth year of transplantation. The probability
      of suffering from cancer is 8.2% and 29.2% at 5 and 15 year, respectively. More
      specifically, after a 15-year follow-up, the probability rate for skin cancer is
      16.4%, solid cancer 12.8%, lymphoproliferative disease (PTLD) 3% and Kaposi's
      sarcoma 2.2%, respectively. PTLD has the highest mortality rate (44% after 12
      months from diagnosis), followed by solid cancer (24%) and Kaposi's sarcoma (8%).
      According to the literature, patient-age is the main risk factor for neoplasm;
      double therapy (Cyclosporine + Azathioprine) can increase both the skin cancer
      and PTLD risk but not the risk of solid cancer. No difference between
      Cyclosporine and Tacrolimus has been observed in the incidence of neoplasm. Both
      in vitro and in vivo studies have documented the ability of Rapamycin to inhibit
      primary and metastatic tumour growth. If these results are also obtained on
      patients, Rapamycin will be of considerable interest for the future of
      immunosuppression. In cancer patients, immunosuppression must always be reduced,
      especially when dealing with PTLD. After standard chemotherapy, patient mortality
      rate due to infectious complications is very high. Therefore, chemotherapy should
      be a second-choice therapy and administered in reduced doses. Many studies have
      documented that lymphocytes B-cells CD20 positive PTLD can be efficiently treated
      with Retuximab.

PMID- 15732049
TI  - Slow-tonic muscle fibers and their potential innervation in the turtle, Pseudemys
      (Trachemys) scripta elegans.
AB  - A description is provided of the ratio of slow-tonic vs. slow- and fast-twitch
      fibers for five muscles in the adult turtle, Pseudemys (Trachemys) scripta
      elegans. The cross-sectional area of each fiber type and an estimation of the
      relative (weighted) cross-sectional area occupied by the different fiber types
      are also provided. Two hindlimb muscles (flexor digitorum longus, FDL; external
      gastrocnemius, EG) were selected on the basis of their suitability for future
      motor-unit studies. Three neck muscles (the fourth head of testo-cervicis, TeC4;
      the fourth head of retrahens capitus collique, RCCQ4; transversalis cervicis,
      TrC) were chosen for their progressively decreasing oxidative capacity. Serial
      sections were stained for myosin adenosine triphosphatase (ATPase), NADH
      diaphorase, and alpha-glycerophosphate dehydrogenase (alpha-GPDH). Conventional
      fiber-type classification was then performed using indirect markers for
      contraction speed and oxidative (aerobic) vs. glycolytic (anaerobic) metabolism:
      i.e., slow oxidative (SO, including slow-twitch and possibly slow-tonic fibers),
      fast-twitch, oxidative-glycolytic (FOG), and fast-twitch glycolytic (Fg) fibers.
      Slow-tonic fibers in the SO class were then revealed by directing the monoclonal
      antibody, ALD-58 (raised against the slow-tonic fiber myosin heavy chain of
      chicken anterior latissimus dorsi), to additional muscle cross sections. All five
      of the tested muscles contained the four fiber types, with the ATPase-stained
      fibers including both slow-tonic and slow-twitch fibers. The extreme
      distributions of SO fibers were in the predominately glycolytic TrC vs. the
      predominately oxidative TeC4 muscle (TrC-SO, 9%; FOG, 20%; Fg, 71% vs. TeC4-SO,
      58%: FOG, 16%; Fg, 25%). Across the five muscles, the relative prevalence of slow
      tonic fibers (4-47%) paralleled that of the SO fibers (9-58%). TeC4 had the
      highest prevalence of slow-tonic fibers (47%). The test muscles exhibited varying
      degrees of regional concentration of each fiber type, with the distribution of
      slow-tonic fibers paralleling that of the SO fibers. In the five test muscles,
      fiber cross-sectional area was usually ranked Fg > FOG > SO, and slow-twitch
      always > slow-tonic. In terms of weighted cross-sectional area, which provides a
      coarse-grain measure of each fiber type's potential contribution to whole muscle
      force, all five muscles exhibited a higher Fg and lower SO contribution to cross
      sectional area than suggested by their corresponding fiber-type prevalence. This
      was also the case for the slow-twitch vs. slow-tonic fibers. We conclude that
      slow-tonic fibers are widespread in turtle muscle. The weighted cross-sectional
      area evidence suggested, however, that their contribution to force generation is
      minor except in highly oxidative muscles, with a special functional role, like
      TeC4. There is discussion of: 1) the relationship between the present results and
      previous work on homologous neck and hindlimb muscles in other nonmammalian
      species, and 2) the potential motoneuronal innervation of slow-tonic fibers in
      turtle hindlimb muscles.

PMID- 15732050
TI  - Absence asymmetry: the evolution of monorchid beetles (Insecta: Coleoptera:
      Carabidae).
AB  - Asymmetrical monorchy, or the complete absence of one testis coupled with the
      presence of its bilateral counterpart, is reported for 174 species of the carabid
      beetle tribes Abacetini, Harpalini, and Platynini (Insecta: Coleoptera:
      Carabidae) based on a survey of over 820 species from throughout the family. This
      condition was not found in examined individuals of any other carabid beetle
      tribes, or of other adephagan beetle families. One monorchid taxon within
      Platynini exhibits symmetrical vasa deferentia at the beginning of the pupal
      stadium, suggesting that developmental arrest of the underdeveloped vas deferens
      takes place in pupation. The point at which development of the testis is
      interrupted is unknown. Complete absence of one organ of a bilateral pair-
      absence asymmetry--is rarely found in any animal clade and among insects is
      otherwise only known for testes in the minute-sized beetles of the family
      Ptiliidae, ovaries in Scarabaeinae dung beetles, and ovaries of some aphids.
      Based on current phylogenetic hypotheses for Carabidae, testis loss has occurred
      independently at least three times, and up to five origins are possible, given
      the variation within Abacetini. Clear phylogenetic evidence for multiple
      independent origins suggests an adaptive or functional cause for this asymmetry.
      A previously posited taxon-specific hypothesis wherein herbivory in the tribe
      Harpalini led to testis loss is rejected. Optimal visceral packing of the beetle
      abdomen is suggested as a general explanation. Specifically, based on the
      function of various organ systems, we hypothesize that interaction of internal
      organs and pressure to optimize organ size and space usage in each system led to
      the multiple origins and maintenance of the monorchid condition. Testes are the
      only redundant and symmetrically paired structures not thought to be
      developmentally linked to other symmetrical structures in the abdomen. Among all
      possible organs, they are the most likely--although the observed frequency is
      very small--to bypass constraints that maintain bilateral symmetry, resulting in
      absence asymmetry. However, based solely on our observations of gross morphology
      of internal organs, no function conclusively explains the ontogenetic loss of one
      testis in these taxa. Unlike the analogous absence asymmetry of organs in other
      animal groups, no dramatic body-form constraint--e.g., snakes and lung loss,
      ptiliid beetles' small body-size and relatively giant sperm--or adaptive scenario
      of improved locomotory performance--e.g., birds and ovary loss due to flight
      constraints-applies to these carabid beetles. We tentatively suggest that testis
      loss is driven wholly by an interaction among the internal organs of these
      beetles, possibly due to selective pressure to maximize the comparatively large
      accessory glands found in these taxa. However, as the ordering of these
      evolutionary events of testis loss and accessory gland size increase is not
      known, large accessory glands might have secondarily evolved to compensate for a
      decreased testicular output.

PMID- 15732051
TI  - Non-FK506-binding protein-12 neuroimmunophilin ligands increase neurite
      elongation and accelerate nerve regeneration.
AB  - Neurotrophic activity of neuroimmunophilin ligands (FK506 and its
      nonimmunosuppressant derivatives) has been assumed to be mediated by the FK506
      binding protein-12 (FKBP-12). We recently showed that activity is retained in
      hippocampal neurons from FKBP-12 knockout mice, indicating that binding to FKBP
      12 is not necessary. Here we show that three nonimmunosuppressant FK506
      derivatives (V-13,450, V-13,629, and V-13,670) that do not bind FKBP-12 (>12.5 mM
      affinity) are equipotent to FKBP-12 ligands (FK506, V-10,367, and V-13,449) for
      increasing neurite elongation in SH-SY5Y cells. One non-FKBP-12 ligand (V-13,670)
      is also shown to accelerate functional recovery and nerve regeneration in the rat
      sciatic nerve crush model. Surprisingly, it exhibited an unusual dose-response
      effect upon oral administration, showing a novel bimodal dose-response for
      behavioral functional recovery and myelination, but not for axonal size,
      suggesting both Schwann cell and neuronal targets. Orally active non-FKBP-12
      neuroimmunophilin ligands may be useful for the treatment of human neurological
      disorders without any potential side effects resulting from FKBP-12 binding.

PMID- 15732052
TI  - Ultrastructure of the epidermal maxilla II-gland of Scutigera coleoptrata
      (Chilopoda, Notostigmophora) and the ground pattern of epidermal gland organs in
      Myriapoda.
AB  - The epidermal maxilla II-gland of Scutigera coleoptrata was investigated using
      light and electron microscopy. The glandular epithelium surrounds a spacious
      integumental cavity at the base of the maxilla II. The gland is formed as a
      compound gland organ that is composed of thousands of epidermal gland units. Each
      of them consists of four different cell types: a secretory cell, an accessory or
      intermediary cell, and a proximal and distal canal cell. The intermediary and the
      two canal cells form a conducting canal. Only in the most distal part of the
      intermediary cell is the canal lined by a cuticle. In the area of the two canal
      cells, the conducting canal is completely covered by a cuticle. The canal passes
      through the cuticle and opens into the spacious integumental cavity, which serves
      as a secretion reservoir. The structural organization of the epidermal maxilla II
      gland was compared to that of other compound epidermal gland organs in Chilopoda
      and Diplopoda. All these glandular organs in Myriapoda share the same ground
      pattern.

PMID- 15732053
TI  - Upper and lower body functional asymmetries in the newborn: do they have the same
      lateral biases?
AB  - It is still an open question as to whether functional asymmetries in the human
      newborn derive from a single lateralized system or multiple subsystems based on
      different neural mechanisms. In the present study, asymmetries in head turning
      were compared to those in leg movements during stepping and placing, with the
      latter also being related to differences in leg mass. The effects of an active
      versus an inactive state or condition were examined for all three behaviors. No
      overall lateral biases were found for head turning or for the first foot to move
      in stepping and placing, and there were no concordances among them; however,
      there was an asymmetry in that the left foot had a shorter onset latency when
      compared to the right foot for both stepping and placing. Findings are discussed
      in terms of what they imply about underlying neural systems that have a bearing
      on expressions of newborn laterality, and also with regard to the impact of
      methodological differences in this area of study.

PMID- 15732054
TI  - Spatial conditional discrimination learning in developing rats.
AB  - The present study established an effective procedure for studying spatial
      conditional discrimination learning in juvenile rats using a T-maze. Wire mesh
      located on the floor of the maze as well as a second, identical T-maze apparatus
      served as conditional cues which signaled whether a left or a right response
      would be rewarded. In Experiment 1, conditional discrimination was evident on
      Postnatal Day (PND) 30 when mesh+maze or maze-alone were the conditional cues,
      but not when mesh-alone was the cue. Experiment 2 confirmed that mesh-alone was
      sufficiently salient to support learning of a simple (nonconditional)
      discrimination. Its failure to serve as a conditional cue in Experiment 1 does
      not reflect its general ineffectiveness as a stimulus. Experiment 3 confirmed
      that the learning shown in Experiment 1 was indeed conditional in nature by
      comparing performance on conditional versus nonconditional versions of the task.
      Experiment 4 showed that PND19 and PND23 pups also were capable of performing the
      task when maze+mesh was the cue; however, the findings indicate that PND19
      subjects do not use a conditional strategy to learn this task. The findings
      suggest postnatal ontogeny of conditional discrimination learning and underscore
      the importance of conditional cue salience, and of identifying task strategies,
      in developmental studies of conditional discrimination learning.

PMID- 15732055
TI  - Cardiac reactivity is associated with changes in negative emotion in 24-month
      olds.
AB  - Despite the call for multilevel observation of negative affect, including
      multiple physiological systems, too little empirical research has been conducted
      in infants and young children, and physiology-affect associations are not
      consistently reported. We examined changes in heart rate, respiratory sinus
      arrhythmia, and preejection period in 24-month-olds across four increasingly
      challenging, emotion-eliciting tasks. We predicted that changes in cardiac
      reactivity would be systematically related to changes in negative affect. Results
      largely support the predictions with one important exception. With increasing
      distress across the tasks, HR increased and RSA decreased. However, no
      significant changes in PEP were observed. HR was associated with negative affect
      during all tasks, and changes in HR were related to changes in negative affect.
      PEP and negative affect were associated, but only marginally so. Within-subject
      analyses confirmed the predicted associations. Finally, the associations between
      physiology and negative affect were different for boys and girls. We discuss
      these results in the context of implications for future research on cardiac
      affect associations in young children.

PMID- 15732056
TI  - Ontogeny of urine preference and its relationship to NH4Cl preference and sodium
      hunger in suckling rat pups.
AB  - We chart the postnatal ontogeny of urine preference in the suckling rat. Twelve
      day-old sucklings, when offered urine, NH4Cl, or NaCl, ingest more urine and
      NH4Cl than NaCl. When rendered sodium hungry by ivc renin or by sodium depletion,
      these sucklings prefer urine and NH4Cl to NaCl, dilute urine, or an NaCl and KCl
      mineral mix equimolar to urine; however, by 18 days of age, urine and NH4Cl are
      no longer preferred to NaCl. Hence, urine preference in the suckling may be
      specific and preparatory for the variety of purposes urine preference serves in
      the adult rat, and it might guide the pup to urinary sodium in the nest. Since
      preference for urine and NH4Cl covary during postnatal development, the high
      preference for NH4Cl in midterm sucklings might be because its ammonium flavor is
      similar to urine.

PMID- 15732057
TI  - Relation of neonatal iron status to individual variability in neonatal
      temperament.
AB  - The relation between indices of neonatal iron status and individual differences
      in neonatal temperament were investigated in a sample of 148 low-income Peruvian
      women and their newborn infants. Using cord blood, at birth we obtained measures
      of neonatal ferritin, serum iron, and hemoglobin. While neonates were still in
      the hospital, their behavior during a structured anthropometry examination was
      videotaped and subsequently coded on four temperament dimensions: activity level,
      negative emotionality, alertness, and soothability. The same dimensions were
      coded using a videotape obtained during a subsequent visit to the neonates'
      homes. Results indicated that lower levels of neonatal hemoglobin and serum iron
      were related to higher levels of negative emotionality and to lower levels of
      alertness and soothability. A similar pattern was found for ferritin, but only
      for females. For the most part, relations between neonatal iron measures and
      neonatal temperament were linear, operating across the full range of iron values.
      Our pattern of iron-temperament results could not be attributed to variation in
      family demographics, low birth weight, gestational age, maternal dietary intake,
      or markers of neonatal illness and maternal diabetes. Our findings are consistent
      with prior research with older infants relating iron deficiency to temperament.
      These results support the importance of increased research on the early
      functional-behavioral consequences of individual differences in iron status as
      well as on the mechanisms that underlie such consequences.

PMID- 15732058
TI  - Ontogeny of the transition from killer to caregiver in dwarf hamsters (Phodopus
      campbelli) with biparental care.
AB  - Biparental Phodopus campbelli and uniparental P. sungorus juvenile litters (2
      males, 2 females) both consumed amniotic fluid and placenta during the birth of
      younger siblings. Three days later, P. campbelli juveniles were most responsive
      to a displaced younger sibling. Thus, P. campbelli are responsive to pups as
      juvenile alloparents and as new parents; however, at intervening ages,
      infanticidal attack (bite) was seen. At 5, 7, 9, 11, or 13 weeks of age, male and
      female P. campbelli were given a 5-min test with an unrelated, 3-day-old,
      anesthetized pup. Females attacked more often than males, yet pup-retrieval rates
      did not differ. Female aggression increased with age and was replaced by
      retrieval behavior 3 days after parturition. Male attack ceased after a birth,
      but parental behavior did not increase, remaining below the rate for new fathers
      tested with their own awake pup. Over repeated testing, behavior in one test did
      not predict behavior in another. Transitions from caregiving alloparent to
      infanticidal adult and back to parental care were clear in females, but less
      discrete with this stimulus paradigm in these highly paternal males.

PMID- 15732059
TI  - Passive responses of young guinea pigs during exposure to a novel environment:
      influences of social partners and age.
AB  - Guinea pig pups exhibit a two-stage, active/passive response during isolation in
      a novel environment that resembles the "protest" and "despair" stages observed in
      some species of primates. The present study examined social and developmental
      influences on the expression of the passive stage of responsiveness in young
      guinea pigs. Both preweaning and periadolescent guinea pigs displayed the passive
      stage during isolation in a novel environment. In preweaning pups and
      periadolescents that had been housed with the mother since birth, the presence of
      the mother in the novel environment prevented the passive stage from occurring.
      Levels of passive responses in the presence of an unfamiliar adult female were
      generally intermediate to those in the other two test conditions; however,
      periadolescents housed only with a peer between weaning and testing exhibited the
      passive stage of responsiveness not only when alone but also when with the mother
      or an unfamiliar female. The findings indicate that the passive responses can
      occur in periadolescent guinea pigs and that the test conditions under which they
      occur depend upon the periadolescents' social housing conditions prior to
      testing. Further, the results are consistent with the hypothesis that responses
      during the second stage constitute "stress-induced sickness behaviors."

PMID- 15732060
TI  - Unusual phenotype with progressive vertebral fusion in a girl with an apparently
      balanced t(10;20)(p11;p13) translocation.
AB  - We report the case of a girl presenting with an unusual form of multiple joint
      fusion. Skeletal abnormalities consisted of radioulnar synostosis and vertebral
      fusions without any carpal, digital or tarsal involvement, and broad ribs and
      clavicles. Spinal X-rays were available from age 4 to 21, demonstrating that the
      spinal involvement was progressive and led to a complete anterior and lateral
      fusion of vertebrae. A complete sequencing of the NOGGIN gene failed to find any
      mutation. In addition, this girl was carrier of an apparently balanced reciprocal
      translocation t(10;20)(p11;p13). We investigated the role of the BMP2A gene as a
      potential candidate gene. Fluorescence in situ hybridization with YAC probes from
      chromosome 20 showed that the BMP2A gene was not disrupted by the translocation
      breakpoint.

PMID- 15732061
TI  - Duplication of chromosome 4q: renal pathology of two siblings.
AB  - We report on two sibs with partial 4q trisomy: dup (4)(q35.2-q31.22) and their
      renal biopsy findings. Both of them show renal hypoplasia, although their
      chromosomal aberration lacks the minimal duplicated region 4q22-q23 and/or 4q25
      q31.3, which had been shown to be associated with urogenital abnormalities and
      thumb malformations in previous reports. From the renal biopsy findings, the two
      sibs were diagnosed as oligonephronia. We summarize the 13 having published cases
      of duplication of chromosome 4q, and examine which segments have a close
      relationship to renal hypoplasia. We suggest that renal hypoplasia may be female
      prone, and may have a close relationship with duplication of 4q33-q34.

PMID- 15732062
TI  - Recombination in a male carrier of two reciprocal translocations involving
      chromosomes 14, 14', 15, and 21 leading to balanced and unbalanced rearrangements
      in offspring.
AB  - We report an unusual case of a familial complex chromosome rearrangement (CCR),
      ascertained through prenatal diagnosis. The fetus carried an apparently balanced
      CCR with a recombinant 3-segment chromosome derived from two paternal reciprocal
      translocations involving both homologs of chromosome 14 and chromosomes 15 and
      21, respectively. A probably normal phenotype was predicted and confirmed after
      birth. His older sister carried an unbalanced karyotype with partial trisomy 14
      and partial monosomy 21, and displayed an apparently normal, paternally derived
      chromosome 14 that resulted from recombination between two derivative
      chromosomes. Fluorescent in situ hybridization (FISH) and molecular studies were
      essential for the characterization of the rearrangement. The "rebuilding,"
      through recombination, of a chromosome involved in two different translocations
      in a progenitor, was demonstrated for the first time by molecular analysis. Our
      family is another good example of how balanced familial complex translocations
      are in a state of flux and can change from one generation to the next.

PMID- 15732063
TI  - An interstitial deletion of chromosome 7 at band q21: a case report and review.
AB  - We report on a girl with moderate developmental delay and mild dysmorphic
      features. Cytogenetic investigations revealed a de novo interstitial deletion at
      the proximal dark band on the long arm of chromosome 7 (7q21.1-q21.3) in all
      analyzed G-banded metaphases of lymphocytes and fibroblasts. Fluorescence in situ
      hybridization (FISH) and molecular studies defined the breakpoints at 7q21.11 and
      7q21.3 on the paternal chromosome 7, with the proximal deletion breakpoint
      between the elastin gene (localized at 7q11.23) and D7S2517, and the distal
      breakpoint between D7S652 and the COL1A2 gene (localized at 7q21.3-q22.1).
      Deletions of interstitial segments at the proximal long arm of chromosome 7 at
      q21 are relatively rare. The karyotype-phenotype correlation of these patients is
      reviewed and discussed. The clinical findings of patients with a deletion at 7q21
      significantly overlap with those of patients with maternal uniparental disomy of
      chromosome 7 (matUPD(7)) and Silver-Russell syndrome (SRS, OMIM 180860).
      Therefore, 7q21 might be considered a candidate chromosomal region for matUPD(7)
      and SRS.

PMID- 15732064
TI  - Place of preimplantation diagnosis in genetic practice.
AB  - Preimplantation genetic diagnosis (PGD) is currently one of the practical options
      available for couples at-risk to avoid the birth of children with genetic and
      chromosomal disorders. Despite its novelty, PGD has already become an alternative
      to traditional prenatal diagnosis, allowing establishing only unaffected
      pregnancies avoiding the risk for pregnancy termination. Indications for PGD have
      currently expanded beyond those practices in prenatal diagnosis, such as late
      onset diseases with genetic predisposition, and preimplantation HLA typing with
      the purpose of establishing potential donor progeny for stem cell treatment of
      siblings, which makes PGD also an important compliment to prenatal diagnosis. The
      fact that more than 1,000 apparently healthy unaffected children have been born
      after PGD suggests its accuracy, reliability, and safety. PGD is presently an
      excellent option for carriers of balanced translocations, and appears to be of
      special value for avoiding age-related aneuploidies in patients of advanced
      reproductive age. The accumulated experience of thousands of PGD cycles for poor
      prognosis in vitro fertilization (IVF) patients provides strong evidence of the
      improvement of clinical outcome, particularly obvious from the reproductive
      history of patients. This makes of practical relevance to inform couples at-risk
      about availability of PGD option, so they make their own choice in avoiding the
      birth of affected offspring and having healthy children of their own.

PMID- 15732065
TI  - Agenesis of tibia with bifid femur, congenital heart disease, and cleft lip with
      cleft palate or tracheoesophageal fistula: possible variants of Gollop-Wolfgang
      complex.
AB  - Two patients with bifurcation of one femur, ipsilateral absence of tibia and one
      partially formed tibia, or bilateral absent tibiae, club feet with normal or
      nearly normal digits, congenital heart disease and, in one case,
      tracheoesophageal fistula; in the second, cleft lip and cleft palate and enlarged
      head with increased fluid and lissencephaly, are described. These appear to be
      unique combinations of defects but overlap with the Gollop-Wolfgang complex is
      present, particularly with the case of possible Gollop-Wolfgang described by Raas
      Rothschild et al.

PMID- 15732066
TI  - The impact of subliminal abandonment and unification cues on eating behavior.
AB  - BACKGROUND: Subliminal presentation of visual abandonment cues leads to greater
      levels of eating, despite a lack of conscious awareness of the information
      involved. The current study examined whether this behavioral impact can be
      countered by the subliminal presentation of contradictory, counterschematic
      information (unification cues). METHOD: Ninety-six nonclinical women were
      presented with subliminal abandonment cues, either preceded or followed by
      neutral or unification cues. The dependent variable was the amount eaten after
      the task. RESULTS: Presenting subliminal unification information before or after
      the subliminal abandonment cue significantly reduced the amount eaten (relative
      to the impact of neutral cues). DISCUSSION: These findings are consistent with a
      model where preconscious processing of unification cues has the effect
      deactivating abandonment schemas, either through inoculation or restoration.
      Preconscious presentation of unification cues might play a role in the broader
      cognitive-behavioral treatment of bulimic behaviors.

PMID- 15732067
TI  - Weight fluctuations during early refeeding period in anorexia nervosa: case
      reports.
AB  - OBJECTIVE: This study reports wide weight fluctuations during a week of early
      refeeding for 2 patients with anorexia nervosa and discusses possible mechanisms.
      METHOD: Laboratory tests that consist of complete blood count, biochemistry
      panel, and serum protein levels were performed. Fluid intake and daily urine
      output of the patients were measured. RESULTS: Laboratory tests were within
      normal limits for both patients except for leukopenia in one patient. By the end
      of the Week 1, both patients had achieved significant weight gain (9 kg and 3 kg,
      respectively) concurrent with edema. Their daily fluid intake and urine output
      measurements indicated increased total body water levels. DISCUSSION: Although
      the pathophysiology of refeeding edema is not entirely understood, it is well
      known that insulin induces sodium retention by increasing distal tubular sodium
      reabsorption. In our patients, refeeding-induced insulin secretion may be chiefly
      responsible for the edema and weight gain during the early refeeding period.

PMID- 15732068
TI  - Maternal core beliefs and children's feeding problems.
AB  - BACKGROUND: Although maternal mental health problems have been implicated in the
      exacerbation of childhood feeding difficulties, little research has assessed the
      contribution of broader maternal cognitions to these problems. The current study
      examined gender differences in the relationships between mothers' core beliefs
      and children's feeding problems. METHODS: One hundred and three mothers of girls
      and 93 mothers of boys (age range, 7-64 months) completed the Young Schema
      Questionnaire and the Child Feeding Assessment Questionnaire. RESULTS: While
      controlling for child age, a clear link between maternal core beliefs and
      perceived feeding difficulties emerged for mothers of girls. In particular,
      abandonment, failure to achieve, dependence and incompetence, enmeshment and
      defectiveness, and shame beliefs were associated with increased reports of
      feeding problems in girls. In contrast, emotional deprivation and subjugation
      beliefs were associated with maternal reports of food fussiness and food refusal
      in boys. CONCLUSIONS: There appears to be a clear role for maternal core beliefs
      in the reporting of feeding difficulties in children, and the specificity of
      these links differs depending on the gender of the child. Further research is
      required to establish the direction of causality and the specificity of these
      relationships.

PMID- 15732069
TI  - The relationship between dieting and body image, body ideal, self-perception, and
      body mass index in Turkish adolescents.
AB  - OBJECTIVE: The current study examined the roles of body image, ideal body weight,
      self-perception, and body mass index (BMI) on the dieting behavior of Turkish
      adolescents. METHOD: The 531 subjects who participated in the study ranged from
      15 to 17 years old and were recruited from five selected high schools in Ankara.
      They completed the Self-Perception Profile for Adolescents (SPPA), the Body Image
      Satisfaction Questionnaire (BISQ), and the Dieting Status Measure (DiSM). Height
      and weight were measured. RESULTS: Dieting adolescents received significantly
      lower scores than nondieters for most of the BISQ items and for the physical
      appearance and global self-worth subscales of the SPPA. A thinner body ideal, the
      physical appearance domain of self-concept, and low global self-worth were the
      predicting factors of frequent dieting. However, BMI and body image
      dissatisfaction were not predicting factors. DISCUSSION: The results indicate
      that a thinner body ideal, low self-worth, and low physical self-concept have
      more significant effects on body dissatisfaction and dieting than being actually
      overweight does. Furthermore, high physical self-concept scores and body
      satisfaction may not necessarily preclude having a thinner body ideal and, hence,
      dieting in girls.

PMID- 15732070
TI  - Eating Disorder Examination-Questionnaire as a measure of change in patients with
      bulimia nervosa.
AB  - OBJECTIVE: The current study evaluated the agreement between the Eating Disorder
      Examination and the Eating Disorder Examination-Questionnaire in assessing eating
      disorder pathology in a sample of women with bulimia nervosa. METHOD: Patients
      with broadly defined bulimia nervosa were enrolled in a double-blind, placebo
      controlled treatment study of fluoxetine, with and without guided self-help. The
      current study presents information from 50 patients with data from both the EDE
      and EDE-Q at study entry and treatment termination. RESULTS: The EDE and EDE-Q
      produced more similar scores for compensatory behaviors (vomiting/laxative use)
      than complex eating-disordered features (binge eating/importance of shape and
      weight) at the pretreatment and posttreatment assessments, and for change during
      the study. DISCUSSION: The EDE and EDE-Q are highly correlated for many of the
      behavioral and attitudinal features of bulimia nervosa. There is substantial
      variability in agreement for individual patients, but on average, the EDE and EDE
      Q will yield similar assessments of eating disorder symptoms and change in
      symptoms over time.

PMID- 15732071
TI  - Two-year prospective study of personality disorders in adults with longstanding
      eating disorders.
AB  - OBJECTIVE: The current study had three objectives: to report the presence of
      personality disorders (PDs) in adults with longstanding eating disorders (EDs) at
      admission to inpatient treatment, and at 1 and 2-year follow-up; to compare the
      frequency of PDs in anorexia nervosa (AN), bulimia nervosa (BN), and eating
      disorder not otherwise specified (EDNOS); and to investigate whether recovered
      patients had lower frequency of PDs. METHOD: Seventy-four patients with a mean
      age of 30 years and long-lasting EDs were assessed with the Structured Clinical
      Interview for DSM-IV Axis-II disorders at admission to inpatient treatment, and
      at 1 and 2-year follow-up. RESULTS: At admission, 57 patients (77%) had one or
      more PDs, whereas 42 patients (57%) had one or more PDs at 2-year follow-up No
      statistically significant differences in frequencies of PDs among patients with
      AN, BN, and EDNOS were found. Recovered patients had a lower frequency of PDs (p
      < .01). DISCUSSION: At 2-year follow-up, there were substantial reductions in the
      frequency of PDs in patients with long-lasting EDs.

PMID- 15732072
TI  - The dearth of psychological treatment studies for anorexia nervosa.
AB  - OBJECTIVE: Anorexia nervosa (AN) was first described more than 130 years ago, yet
      few psychological treatments have been formally studied. Our objective was to
      review the available studies to understand whether these may highlight directions
      for future investigation. METHOD: Medline and PsycINFO were consulted to identify
      relevant treatment studies. Twenty psychotherapy treatment studies were
      identified for review. These were divided in terms of patient age (adolescent vs.
      adult) and type of study (uncontrolled vs. controlled). RESULTS: Without
      exception, adolescent studies (uncontrolled or controlled) involved the parents
      or family in the treatment. The adult studies were much more varied in terms of
      treatments that were compared. Most studies were statistically underpowered and
      only one utilized manualized treatments. More recent investigations have
      attempted to remedy these methodologic shortcomings. DISCUSSION: The review
      highlights the effectiveness of one particular treatment modality for
      adolescents, but emphasizes the compelling need for further and larger systematic
      investigation into treatments for both adolescent and adult AN.

PMID- 15732073
TI  - Assessment of patients with anorexia nervosa: interview versus self-report.
AB  - OBJECTIVE: The current study compared the agreement between the Eating Disorders
      Examination (EDE) and the Eating Disorders Examination-Questionnaire (EDE-Q) in
      the diagnosis and assessment of eating disorder pathology in a sample of women
      with anorexia nervosa. METHOD: First, a physician administered a clinical
      interview to each patient. Then, before hospital admission, all subjects were
      given the EDE-Q and the EDE interview. RESULTS: Results indicate that agreement
      between the EDE and the EDE-Q on the individual items informing the overall
      diagnosis of anorexia nervosa ranges from low to moderate. Agreement for the
      overall diagnosis of anorexia nervosa and for the binge/purge subtype was more
      impressive. Although correlations between subscale scores as well as eating
      disorder behaviors were strong, higher levels of disturbance were consistently
      reported on the EDE-Q than on the EDE interview. DISCUSSION: The pattern of
      findings suggests that the EDE-Q may be used in place of the interviewer-based
      measure when assessing overall diagnosis and subtype, as well as specific, well
      defined features (vomiting/laxative use). However, there was a low level of
      agreement with respect to less-defined features, like binge eating, for which
      significantly higher frequencies were generated by the self-report questionnaire.

PMID- 15732074
TI  - QT interval dispersion and resting metabolic rate in chronic anorexia nervosa.
AB  - OBJECTIVE: During the starvation phase of anorexia nervosa (AN), cardiac and
      skeletal muscle mass decreases, whereas electrocardiographic QT dispersion, a
      marker of arrhythmia risk, increases. QT dispersion during the chronic phase of
      AN and its relationship to resting metabolic rate (RMR) have not been described
      previously and is the subject of the current investigation. METHOD: Six AN
      patients were compared with 10 age-matched control subjects. Serum electrolyte
      levels, electrocardiography, anthropomorphic data, and indirect calorimetry were
      obtained for all participants. RESULTS: Corrected QT interval (QTc) did not
      differ between groups, but QT dispersion was significantly greater in AN
      patients. QT dispersion correlated negatively with resting oxygen consumption and
      RMR. The relationship between QT dispersion and RMR did not persist after
      correcting for lean body mass. CONCLUSIONS: AN patients with a low RMR may be at
      risk for increased QT dispersion. QT dispersion is a widely available and
      inexpensive measure, which may reflect both metabolic status and arrhythmia
      potential.

PMID- 15732075
TI  - An integration of cognitive-behavioral therapy and interpersonal psychotherapy
      for bulimia nervosa: a case study using the case formulation method.
AB  - OBJECTIVE: The current study provides an illustration of an integration of
      cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for the
      treatment of bulimia nervosa (BN), based on the case formulation strategy.
      METHOD: A 25-year-old Hispanic female referred herself for the treatment of
      eating difficulties and depressed mood. Diagnostic criteria were met for BN,
      major depressive episode, and alcohol abuse. Components of both CBT and IPT were
      utilized throughout the course of treatment. RESULTS: CBT techniques appeared to
      be most effective in eliminating binge eating and binge drinking behavior,
      whereas IPT techniques seemed to be most effective in reducing purging behavior.
      Results revealed that the client was no longer experiencing clinically
      significant symptoms of BN, depression, or alcohol abuse at end of treatment and
      follow-up (18 months after treatment onset). DISCUSSION: Findings support the
      integration of CBT and IPT for the treatment of BN and, potentially, other eating
      disorders.

PMID- 15732076
TI  - Effects of exposure to unrealistic promises about dieting: are unrealistic
      expectations about dieting inspirational?
AB  - OBJECTIVE: The false-hope syndrome suggests that unrealistic expectations about
      dieting set dieters up for failure and then promote renewed efforts at weight
      loss. Many dieters believe the inflated promises typical of diet advertisements,
      which may be the source of at least some of their unrealistic expectations. Diet
      advertisements promoting unrealistic expectations were expected to inspire
      restrained eaters to diet and lead to enhanced self-perceptions, relative to more
      circumspect advertisements. METHOD: Female undergraduates rated their
      expectations in response to a control advertisement or to advertisements
      containing realistic, moderately unrealistic, or highly unrealistic promises of
      dieting. Participants then rated their self-perceptions and participated in an
      apparent "taste-test". RESULTS: Restrained eaters had higher expectations for
      themselves than did unrestrained eaters, and restrained and unrestrained eaters
      had similar expectations concerning dieting for others. Those who viewed the
      advertisements containing unrealistic expectations ate fewer cookies ad libitum
      than did those who viewed the realistic or control advertisements. DISCUSSION:
      This finding is consistent with the suggestion that unrealistic expectations
      contribute to the decision to change oneself.

PMID- 15732077
TI  - Non-fat-phobic anorexia nervosa in British South Asian adolescents.
AB  - OBJECTIVE: The current study investigated the clinical features of British South
      Asian adolescent females presenting with low weight in the absence of organic
      disease. METHODS: The authors performed a retrospective case note study of South
      Asian British female adolescents presenting with weight loss/anorexia nervosa to
      psychiatric clinics and matched White English peers presenting with low weight.
      RESULTS: South Asian patients presented more frequently with loss of appetite (p
      = .01) and less frequently with fat phobia (p = .032) and weight preoccupation (p
      = .001). South Asians also had significantly more satisfactory relationships with
      their nuclear family and peers (p = .03). DISCUSSION: Differing symptom profiles
      for anorexia nervosa need to be taken into account when assessing patients from
      different cultures. South Asian adolescents may present with a non-fat-phobic
      form of anorexia nervosa. This has clinical and epidemiologic implications.
      Further investigation is warranted to assess the nosologic status of this group.

PMID- 15732078
TI  - Psychosocial correlates, outcome, and stability of abnormal adolescent eating
      behavior in community samples of young people.
AB  - OBJECTIVE: The current study investigated psychosocial correlates of abnormal
      adolescent eating behavior at three times during adolescence and young adulthood
      and its association with psychiatric diagnosis in young adulthood in a community
      sample. METHOD: Sixty-four (10.5%) high-risk subjects (mean age 15 years) with
      abnormal eating behavior were identified at Time 1, another 252 (16.9%) were
      identified at Time 2 (mean age 16.2 years), and 164 (16.9%) were identified at
      Time 3 (mean age 19.7 years) and compared with three control groups matched for
      age and gender. Dependent measures included emotional and behavioral problems,
      life events, coping capacities, self-related cognition, social network, and
      family functions. Outcome was measured additionally by structured psychiatric
      interviews, and stability of abnormal eating behavior was studied in a
      longitudinal sample of 330 subjects. RESULTS: Few subjects showed more than one
      of five criteria of abnormal eating behavior. High-risk subjects shared a very
      similar pattern at all three times. They were characterized by higher scores for
      emotional and behavioral problems, more life events including more negative
      impact, less active coping, lower self-esteem, and less family cohesion. Among 10
      major psychiatric disorders, only clinical eating disorders at Time 3 shared a
      significant association with abnormal eating disorder at the same time whereas
      high-risk status at Times 1 and 2 did not predict any psychiatric disorder at
      Time 3. Stability of abnormal eating behavior across time was very low. Stability
      of abnormal eating behavior across time was very low. DISCUSSION: Abnormal eating
      behavior in adolescence and young adulthood is clearly associated with various
      indicators of psychosocial maladaption. In adolescence, it does not significantly
      predict any psychiatric disorder including eating disorder in young adulthood and
      it is predominantly a transient feature.

PMID- 15732079
TI  - The role of stress in the association between low self-esteem, perfectionism, and
      worry, and eating disorders.
AB  - OBJECTIVE: Several theorists have hypothesized that stressful situations may
      trigger abnormal eating and even eating disorders in predisposed people. The
      purpose of the current study was to assess whether a stressful situation would
      reveal an association between perfectionism, low self-esteem, worry, and body
      mass index (BMI) and measures of eating disorder symptoms in female high school
      students. METHOD: A sample of 145 female high school students completed the
      Eating Disorder Inventory, the Multidimensional Perfectionism Scale, the Penn
      State Worry Questionnaire, and the Self Liking and Competence Scale three times-
      on an average school day, on the day of an examination, and on the day the
      subjects received the results of that examination. Linear regression analysis was
      performed to verify whether the dimensions of perfectionism were associated with
      the measures of eating disorders. RESULTS: Low self-esteem, worry, and parental
      criticism (a dimension of perfectionism) were associated with the measures of
      eating disorders only during the stressful situation, whereas concern over
      mistakes (another dimension of perfectionism) was associated in both stressful
      and nonstressful situations. DISCUSSION: The results suggest that in nonclinical
      female individuals, stress might bring out a previously absent association
      between some psychological predisposing factors for eating disorders and an
      actual desire or plan to lose weight. Such a finding suggests that stress may
      stimulate behaviors related to eating disorders in a predisposed personality.

PMID- 15732080
TI  - A QF-PCR system to detect chromosome 13 aneuploidy from as few as ten cells.
AB  - Complete and partial trisomies of chromosome 13 are characterized by abnormal
      fetal development and birth defects. Despite the severe abnormalities associated
      with trisomy 13, some couples elect not to undergo invasive prenatal diagnosis
      (PND) due to the 0.5%-1.0% risk of pregnancy loss. As a result, current studies
      are focusing on refining non-invasive prenatal diagnostic techniques, such as
      screening fetal cells isolated from maternal blood or cervical smears. As these
      techniques only provide a limited number of cells for analysis, any progress in
      this field depends on the development of a highly sensitive genetic screening
      strategy. We have developed a quantitative fluorescent PCR (QF-PCR) system
      capable of detecting chromosome 13 aneuploidy from as few as 10 cells. The system
      was further validated by screening 13 amniocyte samples, three of which had been
      diagnosed by FISH as having chromosomal abnormalities involving chromosome 13. In
      all cases, the QF-PCR results were concordant with those obtained using FISH. The
      high reliability (99%) and accuracy (96%) of the QF-PCR system at the 10 cell
      level makes this technique ideal for use in non-invasive PND.

PMID- 15732081
TI  - Eating Disorder Examination-Questionnaire with and without instruction to assess
      binge eating in patients with binge eating disorder.
AB  - OBJECTIVE: The current study examined whether adding written definitions and
      examples of binge eating to the Eating Disorder Examination-Questionnaire
      enhances its utility to assess binge frequency in patients with binge eating
      disorder (BED). METHOD: Eighty-nine women and men with BED completed the EDE-Q
      (without instruction; n = 37) or the EDE-Q-I (with instruction; n = 52) before
      receiving the EDE interview. Binge frequency was measured as the number of binge
      days (days on which one or more objective binge episodes occurred) over the past
      28 days. RESULTS: Binge frequency correlations between the EDE and EDE-Q-I were
      strongly significant (r = .543, p = .000), whereas correlations between the EDE
      and EDE-Q were not significant (r = .197, p = .242). DISCUSSION: Providing brief
      detailed instructions improves the performance of the EDE-Q when evaluating binge
      eating in patients with BED. This suggests that, with relatively minor
      modifications, the EDE-Q may be a viable alternative to the EDE in assessing
      binge frequency in this population.

PMID- 15732082
TI  - Malformations of the axial skeleton in Museum Vrolik I: homeotic transformations
      and numerical anomalies.
AB  - The Museum Vrolik collection of anatomical specimens in Amsterdam, The
      Netherlands, comprises over 5,000 specimens of human and animal anatomy,
      embryology, pathology, and congenital anomalies. Recently, we rediagnosed a
      subset of the collection comprising dried human trunk skeletons and cranial base
      preparations presenting with homeotic transformations (vertebral phenotypic
      shifts) and numerical vertebral anomalies. We identified 11 trunk skeletons with
      either anterior or posterior homeotic transformations (AHT or PHT), 5 trunk
      skeletons with either less or more than the normal number of vertebrae, and well
      over a hundred cranial base preparations with either AHT (atlas-assimilation) or
      PHT (occipital vertebra). We found that, although homeotic transformations and
      numerical anomalies are distinct conditions, both can be described in terms of
      mismatch between homeotic patterning and morphological segmentation of the
      paraxial mesoderm. Therefore these two processes are perhaps not as tightly
      linked as they may seem on the basis of recent molecular studies. In homeotic
      transformations there is a constant mismatch between homeotic patterning and
      morphological segmentation throughout the affected region of the vertebral
      column. In numerical anomalies there is a variable mismatch between homeotic
      patterning and morphological segmentation, either because of stretching or
      squeezing of the homeotic pattern or because of oligo- or polysegmentation of the
      presomitic mesoderm (PSM). Homeotic transformations of the axial skeleton have an
      incidence of about 1%-5%, apart from their occurrence in malformation syndromes.
      Of the various etiological possibilities, explaining their frequent but mostly
      sporadic occurrence, maternal hyperthermia seems an attractive candidate.

PMID- 15732083
TI  - Baller-Gerold syndrome after fetal exposure to sodium valproate.

PMID- 15732084
TI  - Men and therapy: critical concepts, theoretical frameworks, and research
      recommendations.
AB  - Scholars are increasingly recognizing the existence of multiple evolving
      conceptions of masculinity and the need for psychologists to better attend to
      masculinity-related constructs and their implications for men's lives. This
      article seeks to respond to this need by (a) reviewing research linking
      masculinity-related constructs to clinically relevant issues, (b) providing
      suggestions for building effective therapeutic relationships with male clients,
      (c) describing the role that culture and racism may play in male clients' lives,
      and (d) offering recommendations for future research.

PMID- 15732085
TI  - Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER
      abnormalities.
AB  - Peroxisome deficiency in men causes severe pathology in several organs,
      particularly in the brain and liver, but it is still unknown how metabolic
      abnormalities trigger these defects. In the present study, a mouse model with
      hepatocyte-selective elimination of peroxisomes was generated by inbreeding Pex5
      loxP and albumin-Cre mice to investigate the consequences of peroxisome deletion
      on the functioning of hepatocytes. Besides the absence of catalase-positive
      peroxisomes, multiple ultrastructural alterations were noticed, including
      hepatocyte hypertrophy and hyperplasia, smooth endoplasmic reticulum
      proliferation, and accumulation of lipid droplets and lysosomes. Most prominent
      was the abnormal structure of the inner mitochondrial membrane, which bore some
      similarities with changes observed in Zellweger patients. This was accompanied by
      severely reduced activities of complex I, III, and V and a collapse of the
      mitochondrial inner membrane potential. Surprisingly, these abnormalities
      provoked no significant disturbances of adenosine triphosphate (ATP) levels and
      redox state of the liver. However, a compensatory increase of glycolysis as an
      alternative source of ATP and mitochondrial proliferation were observed. No
      evidence of oxidative damage to proteins or lipids nor elevation of oxidative
      stress defence mechanisms were found. Altered expression of peroxisome
      proliferator-activated receptor alpha (PPAR-alpha) regulated genes indicated that
      PPAR-alpha is activated in the peroxisome-deficient cells. In conclusion, the
      absence of peroxisomes from mouse hepatocytes has an impact on several other
      subcellular compartments and metabolic pathways but is not detrimental to the
      function of the liver parenchyma. Supplementary material for this article can be
      found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270
      9139/suppmat/index.html).

PMID- 15732086
TI  - Marketing mental health to men: theoretical and practical considerations.
AB  - The current paper addresses the importance of and relevant challenges pertaining
      to the marketing of mental health to men. Included are pertinent definitions, a
      review of related research, and a discussion of recent large-scale gender
      specific mental health campaigns. In addition, central aspects of the social
      marketing framework considered to be particularly useful for addressing men's
      resistance to help seeking are reviewed. Suggestions for future research topics
      are also provided.

PMID- 15732087
TI  - The study of men and masculinity as an important multicultural competency
      consideration.
AB  - Gender issues in multicultural competencies do not generally include the study of
      men and masculinity. This article outlines a rationale for the inclusion of men
      and masculinity by drawing parallels with Whiteness and privilege as integral
      aspects of multicultural competency. Additionally, by including the study of men
      and masculinity into multicultural competency, issues such as heterosexism,
      patriarchy, homophobia, and sexism that are aspects of dominant masculinity can
      be addressed. Simultaneously, training clinicians to work with men may mean more
      effective and improved services than currently available. The article concludes
      with several multicultural competencies for clinicians when working with men that
      use Sue, Arredondo, and McDavis (1992) framework of multicultural competencies.

PMID- 15732088
TI  - Evidence-based assessment with men.
AB  - Men are almost universally underrepresented in psychological clinics and
      practices in the United States. One possible explanation for this
      underrepresentation is that men frequently conceal or obscure their emotional
      difficulties as a consequence of masculine gender role socialization. Men who
      subscribe to traditional, Western masculine values may be inclined to hide,
      minimize, or otherwise have difficulty expressing their psychological suffering,
      rendering this suffering difficult for clinicians to observe, diagnose, and
      treat. This manuscript describes an approach to the assessment process with men
      that integrates clinical reports on assessment and psychotherapy with men, values
      pertaining to our culture's construction of traditional masculinity, and
      empirical findings on psychological disorders more commonly observed in men.

PMID- 15732089
TI  - Using the conformity to masculine norms inventory to work with men in a clinical
      setting.
AB  - Given that gender roles are increasingly viewed as salient in clinical work with
      men, this article describes a process of exploring masculine gender roles with
      male clients in therapy by using the Conformity to Masculine Norms Inventory
      (CMNI). Specifically, this article (a) discusses how men's degree of conformity
      to masculine norms may be connected to a variety of benefits and costs, (b)
      describes the CMNI as a tool that can be used to explore men's degree of
      conformity to masculine norms, (c) describes a process by which to use the CMNI
      to explore the relevance of men's masculine selves to their presenting concerns,
      and (d) illustrates the process with a case example. As such, the paper is
      intended to provide a systematic procedure for clinicians working with men who
      want to explore the benefits and costs that both conformity, and nonconformity,
      to specific masculinity norms brings for male clients.

PMID- 15732090
TI  - Toxic masculinity as a barrier to mental health treatment in prison.
AB  - The current article addresses gender issues that become magnified in prison
      settings and contribute to heightened resistance in psychotherapy and other forms
      of mental health treatment. Toxic masculinity involves the need to aggressively
      compete and dominate others and encompasses the most problematic proclivities in
      men. These same male proclivities foster resistance to psychotherapy. Some of the
      stresses and complexities of life in men's prisons are explored. The relation
      between hegemonic masculinity and toxic masculinity is examined. The discussion
      proceeds to the interplay between individual male characteristics and
      institutional dynamics that intensify toxic masculinity. A discussion of some
      structural obstacles to mental health treatment in prison and resistances on the
      part of prisoners is followed by some general recommendations for the therapist
      in this context.

PMID- 15732091
TI  - Social scientific paradigms of masculinity and their implications for research
      and practice in men's mental health.
AB  - Clinical researchers and practitioners are increasingly aware of the need for
      quality theory, research, and intervention in men's mental health. Successful
      work in this area requires an understanding of the multitude of ways that gender,
      and more specifically masculinities, can be conceptualized beyond a sole focus on
      sex differences between men and women. Drawing from a range of social sciences in
      addition to psychology, the authors consider several theoretical, research, and
      clinical directions that can follow from social learning, psychodynamic, social
      constructionist, and feminist paradigms. It is concluded that thinking deeply and
      critically within different paradigms of masculinity is critical for progress in
      both research and practice.

PMID- 15732092
TI  - Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with
      chronic genotype 2 and 3 hepatitis C.
AB  - BILN-2061, a specific and potent peptidomimetic inhibitor of the HCV NS3
      protease, has recently been shown to markedly lower serum hepatitis C virus (HCV)
      RNA levels in patients chronically infected with HCV genotype 1 in three 2-day
      proof of principle studies. The aim of the current study was to assess the
      antiviral efficacy of BILN-2061 in patients with genotypes 2 and 3 HCV infection.
      The antiviral efficacy, pharmacokinetics, and tolerability of 500 mg twice-daily
      BILN-2061 given as monotherapy for 2 days in 10 patients chronically infected
      with non-genotype 1 HCV (genotype 2: n = 3; genotype 3: n =7) and minimal liver
      fibrosis (Ishak score 0-2) were assessed in a placebo-controlled (placebo n = 2),
      double-blind pilot study. HCV-RNA levels decreased by > or =1 log(10) copies/mL
      in 4 of 8 patients treated with BILN-2061. One patient showed a weak response of
      <1 log(10) copies/mL. Three of 8 treated patients showed no response. There was
      no correlation between baseline viral concentration or genotype and response.
      BILN-2061 exhibited good systemic exposure after oral administration and was well
      tolerated. In conclusion, the antiviral efficacy of the HCV serine protease
      inhibitor BILN-2061 is less pronounced and more variable in patients with HCV
      genotype 2 or 3 infection compared with previous results in patients with HCV
      genotype 1. A lower affinity of BILN-2061 for the NS3 protease of genotypes 2 and
      3 HCV is most likely a major contributor to these findings.

PMID- 15732093
TI  - Changes in the neuromuscular synapse induced by an antibody against gangliosides.
AB  - In this study, we used a monoclonal IgM antibody from a patient with a pure motor
      chronic demyelinating polyneuropathy, which binds specifically to the complex
      gangliosides GM(2), GalNAc-GD(1a), and GalNAc-GM(1b), which appear to have a
      common epitope of -[GalNAcbeta1-4Gal(3-2alphaNeuAc)beta1]. This was done for the
      following reasons: (1) to localize these gangliosides in specific cellular
      components of the neuromuscular junction (NMJ), and (2) to describe the anti
      ganglioside antibody-induced structural and functional changes in the NMJs to
      gain insight into the role of gangliosides in the synaptic function. Using
      immunofluorescence techniques, we found that these gangliosides are located only
      in the presynaptic component of the motor end-plates, both in nerve terminals and
      in Schwann cells. After 2 weeks of continued passive transfer of the IgM
      monoclonal antibody over the mouse levator auris longus muscle, electromyography
      showed an axonal or NMJ disorder. Morphology showed important nerve terminal
      growth and retraction changes. Using intracellular recording electrophysiology,
      we found neurotransmitter release alterations, including quantal content
      reduction and an immature expression of voltage-dependent calcium channels
      similar to what occurred during NMJ development and regeneration. These changes
      were complement independent. The results showed that these gangliosides were
      involved in the reciprocal Schwann cell-nerve terminal interactions, including
      structural stability and neurotransmission.

PMID- 15732094
TI  - Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation.
AB  - Recently, two missense mutations (N88S, S90L) in the Berardinelli-Seip congenital
      lipodystrophy gene have been identified in autosomal dominant distal hereditary
      motor neuropathy and Silver syndrome. We report the phenotypic consequences of
      the N88S mutation in 90 patients of 1 large Austrian family and two unrelated
      German families. Variation in the clinical and electrophysiological phenotype
      enabled us to distinguish six subtypes. In 4.4%, the disorder was not penetrant.
      Twenty percent of the patients were subclinically affected; some of these
      patients could only be detected by pathological nerve conduction studies. A
      distal hereditary motor neuropathy type V phenotype characterized by predominant
      hand muscle involvement was found in 31.1%, whereas 14.5% showed typical Silver
      syndrome with amyotrophy of the small hand muscles and spasticity of the lower
      extremities. Moreover, the phenotype present in 20% was compatible with Charcot
      Marie-Tooth disease. In 10%, the clinical diagnosis of pure or complicated
      hereditary spastic paraparesis was made. Electrophysiological studies showed an
      axonal neuropathy but also chronodispersion of compound motor action potentials
      and conduction blocks. Sensory nerve conduction studies were rarely pathological.
      Our study indicates that the dominant N88S mutation in the Berardinelli-Seip
      congenital lipodystrophy gene 2 leads to a broad spectrum of motor neuron
      disorders.

PMID- 15732095
TI  - Effective gene therapy for an inherited CNS disease in a large animal model.
AB  - Genetic diseases affecting the brain typically have widespread lesions that
      require global correction. Lysosomal storage diseases are good candidates for
      central nervous system gene therapy, because active enzyme from genetically
      corrected cells can be secreted and taken up by surrounding diseased cells, and
      only small amounts of enzyme (<5% of normal) are required to reverse storage
      lesions. Injection of gene transfer vectors into multiple sites in the mouse
      brain has been shown to mediate widespread reversal of storage lesions in several
      disease models. To study a brain closer in size to the human brain, we evaluated
      the extent of storage correction mediated by a limited number of adeno-associated
      virus vector injections in the cat model of human alpha-mannosidosis. The treated
      cats showed remarkable improvements in clinical neurological signs and in brain
      myelination assessed by quantitative magnetic resonance imaging. Postmortem
      examination showed that storage lesions were greatly reduced throughout the
      brain, even though gene transfer was limited to the areas surrounding the
      injection tracks. The data demonstrate that widespread improvement of
      neuropathology in a large mammalian brain can be achieved using multiple
      injection sites during one operation and suggest that this could be an effective
      treatment for the central nervous system component of human lysosomal enzyme
      deficiencies.

PMID- 15732096
TI  - False-positive SCA8 gene test in a patient with pathologically proven multiple
      system atrophy.

PMID- 15732097
TI  - Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms
      of Alexander disease.
AB  - Alexander disease is a progressive, usually fatal neurological disorder defined
      by the widespread and abundant presence in astrocytes of protein aggregates
      called Rosenthal fibers. The disease most often occurs in infants younger than 2
      years and has been labeled a leukodystrophy because of an accompanying severe
      myelin deficit in the frontal lobes. Later onset forms have also been recognized
      based on the presence of abundant Rosenthal fibers. In these cases, clinical
      signs and pathology can be quite different from the infantile form, raising the
      question whether they share the same underlying cause. Recently, we and others
      have found pathogenic, de novo missense mutations in the glial fibrillary acidic
      protein gene in most infantile patients examined and in a few later onset
      patients. To obtain further information about the role of glial fibrillary acidic
      protein mutations in Alexander disease, we analyzed 41 new patients and another 3
      previously described clinically, including 18 later onset patients. Our results
      show that dominant missense glial fibrillary acidic protein mutations account for
      nearly all forms of this disorder. They also significantly expand the catalog of
      responsible mutations, verify the value of magnetic resonance imaging diagnosis,
      indicate an unexpected male predominance for the juvenile form, and provide
      insights into phenotype-genotype relations.

PMID- 15732098
TI  - Unusual variants of Alexander's disease.
AB  - The purpose of this study was to describe unusual variants of Alexander's
      disease. We studied 10 patients who did not meet previously established magnetic
      resonance imaging (MRI) criteria for Alexander's disease, but for whom this
      diagnosis was considered because of Rosenthal fibers at histological examination
      or presence of some MRI features suggestive of Alexander's disease. Sequence
      analysis of the GFAP gene was performed. In eight patients, MRI results showed
      predominantly posterior fossa lesions, especially multiple tumor-like brainstem
      lesions. One patient had asymmetrical frontal white matter abnormalities and
      basal ganglia abnormalities. One patient (Patient 10) developed degeneration of
      the frontal white matter. In nine patients, a mutation was found that was
      concluded to be pathogenic, because the mutation was de novo (five patients), a
      known mutation was found (two patients), or assembly of the glial fibrillary
      acidic protein was abnormal in cultured cells (two patients). In Patient 10, a
      DNA variation was found that was also present in the patient's clinically
      unaffected father and was concluded to be a polymorphism. In conclusion, DNA
      diagnostics is warranted in patients who display MRI features suggestive of
      Alexander's disease, even if they do not meet the full set of previously
      established MRI criteria.

PMID- 15732100
TI  - Puffer fish poisoning, Guillain-Barre syndrome and persistent sodium channels.

PMID- 15732101
TI  - Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy.
AB  - Senataxin recently was identified as the mutated gene in ataxia-oculomotor
      apraxia 2, which is characterized by ataxia, oculomotor apraxia, and increased
      alpha-fetoprotein levels. In this study, we evaluated 24 ataxic patients from 10
      French-Canadian families. All cases have a homogeneous phenotype consisting of a
      progressive ataxia appearing between 2 and 20 (mean age, 14.8) years of age with
      associated dysarthria, saccadic ocular pursuit, distal amyotrophy, sensory and
      motor neuropathy, and increased alpha-fetoprotein levels but absence of
      oculomotor apraxia. Linkage disequilibrium was observed with markers in the
      ataxia-oculomotor apraxia 2 locus on chromosome 9q34. We have identified four
      mutations in senataxin in the French-Canadian population including two novel
      missense mutations: the 5927T-->G mutation changes the leucine encoded by codon
      1976 to an arginine in the helicase domain (L1976R), and the 193G-->A mutation
      changes a glutamic acid encoded by codon 65 into a lysine in the N-terminal
      domain of the protein (E65K). The common L1976R mutation is shared by 17 of 20
      (85%) carrier chromosomes. The study of this large French-Canadian cohort better
      defines the phenotype of this ataxia and presents two novel mutations in
      senataxin including the more common founder mutation in the French-Canadian
      population.

PMID- 15732103
TI  - Depressive symptoms, sex, and risk for Alzheimer's disease.
AB  - Depression associates with increased risk for dementia and Alzheimer's disease
      (AD), although it is unclear whether it represents an actual risk factor or a
      prodrome. To determine the relative hazard of premorbid depressive symptomatology
      for development of dementia and AD, we studied risk for incident dementia and AD
      over a 14-year period in 1,357 community-dwelling men and women participating in
      the 40-year prospective Baltimore Longitudinal Study of Aging. Screening for
      depressive symptoms, comprehensive medical and neuropsychological evaluations
      were prospectively collected every 2 years. Time-dependent proportional hazards
      of development of AD or dementia were calculated separately for men and women,
      with symptoms of depression detected at 2-, 4-, and 6-year intervals before onset
      of dementia symptoms. Vascular risk factors were analyzed as covariates.
      Premorbid depressive symptoms significantly increased risk for dementia,
      particularly AD in men but not in women. Hazard ratios were approximately two
      times greater than for individuals without history of depressive symptoms, an
      effect independent of vascular disease. We conclude that the impact of depressive
      symptoms on risk for dementia and AD may vary with sex. Further studies assessing
      separately the role of depression as a risk factor in men and women are
      necessary.

PMID- 15732104
TI  - Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG.
AB  - In generalized myasthenia gravis (MG) patients without detectable acetylcholine
      receptor (AChR) antibodies (SNMG), the thymus is often reported as "normally
      involuted." We analyzed thymic compartments in 67 patients with generalized MG,
      with AChR antibodies (AChR+, n = 23), with muscle-specific kinase (MuSK)
      antibodies (MuSK+, n = 14) or with neither (MuSK-, n = 30), and in 11 non-MG
      controls. Four of 14 MuSK+ thymi had rare small germinal centers, but overall
      they were not different from age-matched controls. However, approximately 75%
      MuSK- samples showed lymph node-type infiltrates similar to those in AChR+
      patients, but with fewer germinal centers. These variations may explain some
      apparent differences in responses to thymectomy in SNMG.

PMID- 15732105
TI  - Genetic influence on rolandic epilepsy.

PMID- 15732106
TI  - Familial Parkinson's disease: clinical and genetic analysis of four Basque
      families.
AB  - During the last few years several loci have been linked to Mendelian forms of
      Parkinson's disease (PD). To date, 5 causative genes of 10 identified loci are
      known, and they have provided enormous insight into the molecular pathways
      involved in this common neurodegenerative disorder. One of the recently
      identified loci, PARK8, causes autosomal dominant PD with, apparently, various
      degrees of abnormal deposition of alpha-synuclein or tau in the neuronal cells in
      the pedigrees currently reported. We genetically characterized four Basque
      families and found evidence for linkage of autosomal dominant PD to the PARK8
      locus, with a maximum 2-point logarithm of odds score of 3.21 (theta = 0.00) for
      marker D12S345. The clinical features of these families are those of typical PD,
      including good response to levodopa therapy, rigidity, and akinesia, and a mean
      age of 55 years at disease onset.

PMID- 15732108
TI  - Clinical and positron emission tomography of Parkinson's disease caused by LRRK2.
AB  - We have recently identified mutations in a gene leucine-rich repeat kinase-2
      (LRRK2), which cause autosomal dominant Parkinson's disease. Here, we describe
      two families with autosomal dominant Parkinson's disease caused by a LRRK2 G2019S
      mutation. We present here a clinical description of patients, including 6-(18)F
      fluoro-L-dopa positron emission tomography and discuss the potential implications
      of this mutation, which alters a conserved residue in a domain required for
      kinase activation.

PMID- 15732107
TI  - Acute tetrodotoxin-induced neurotoxicity after ingestion of puffer fish.
AB  - This study documents the effects of puffer-fish poisoning on peripheral nerve.
      Excitability measurements investigated membrane properties of sensory and motor
      axons in four patients. The median nerve was stimulated at the wrist, with
      compound muscle potentials recorded from abductor pollicis brevis and compound
      sensory potentials from digit 2. Stimulus-responses, strength-duration time
      constant (tau(SD)), threshold electrotonus, and current-threshold relations were
      recorded. The urine of each patient tested positive for tetrodotoxin. Compared
      with controls, axons were of higher threshold, compound muscle action potentials
      and compound sensory nerve action potentials were reduced in amplitude, latency
      was prolonged, and tau(SD) was reduced. In recovery cycles, refractoriness,
      superexcitability, and late subexcitability were decreased. Threshold
      electrotonus of motor axons exhibited distinctive abnormalities with less
      threshold decline than normal on depolarization and greater threshold increase on
      hyperpolarization (p < 0.0005 for each patient). The changes in excitability were
      reproduced in a mathematical model by reducing sodium (Na(+)) permeabilities by a
      factor of two. This study confirms that the neurotoxic effects of puffer-fish
      poisoning can be explained by tetrodotoxin blockade of Na(+) channels. It
      demonstrates the ability of noninvasive nerve excitability studies to detect
      Na(+) channel blockade in vivo and also the utility of mathematical modeling to
      aid interpretation of altered excitability properties in disease.

PMID- 15732111
TI  - Interaction of alpha-synuclein and tau genotypes in Parkinson's disease.
AB  - To determine whether the microtubule-associated protein tau (MAPT) and alpha
      synuclein (SNCA) genes interact to confer Parkinson's disease (PD)
      susceptibility, we conducted a study of 557 case-control pairs. There was an
      increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes
      as compared with persons with neither (odds ratio, 1.96; 95% confidence interval,
      1.34-2.86; p = 0.0003). However, the combined effect of the two genotypes was the
      same as for either of the genotypes alone (separate and equal). These findings
      are consistent with in vitro experiments that revealed tau-mediated
      fibrillization of alpha-synuclein protein at low concentrations (dose threshold
      effect).

PMID- 15732112
TI  - Intravenous immunoglobulin response and evidence for pathogenic antibodies in a
      case of complex regional pain syndrome 1.

PMID- 15732113
TI  - Assessment of nerve degeneration by gadofluorine M-enhanced magnetic resonance
      imaging.
AB  - Nerve injury represents a major cause of disability. In the peripheral nervous
      system, nerves have the capacity to regrow but within weeks after injury, it is
      impossible to clarify whether proper regeneration is under way or is failing. In
      this experimental study, we report on a novel tool to assess nerve outgrowth in
      vivo. After systemic application, the novel gadolinium-based magnetic resonance
      (MR) contrast agent Gadofluorine M (Gf) selectively accumulated and persisted in
      nerve fibers undergoing Wallerian degeneration causing bright contrast on T1
      weighted MR images. Gf enhancement on MR imaging was present already at 48 hours
      within the entire nerve segments undergoing Wallerian degeneration, and
      subsequently disappeared from proximal to distal parts in parallel to regrowth of
      nerve fibers. Most importantly, Gf enhancement persisted in nonregenerating,
      permanently transected nerves. Our novel Gf-based MR imaging methodology holds
      promise for clinical use to bridge the diagnostic gap between nerve injury and
      completed nerve regeneration, and to determine the necessity for neurolysis and
      engraftment if spontaneous regeneration is not successful.

PMID- 15732114
TI  - Sensorimotor retuning [corrected] in complex regional pain syndrome parallels
      pain reduction.
AB  - Patients with complex regional pain syndrome (CRPS) and intractable pain showed a
      shrinkage of cortical maps on primary (SI) and secondary somatosensory cortex
      (SII) contralateral to the affected limb. This was paralleled by an impairment of
      the two-point discrimination thresholds. Behavioral treatment over 1 to 6 months
      consisting of graded sensorimotor retuning led to a persistent decrease in pain
      intensity, which was accompanied by a restoration of the impaired tactile
      discrimination and regaining of cortical map size in contralateral SI and SII.
      This suggests that the reversal of tactile impairment and cortical reorganization
      in CRPS is associated with a decrease in pain.

PMID- 15732115
TI  - Cerebral fat embolism: usefulness of magnetic resonance spectroscopy.
AB  - We report a case of cerebral fat embolism which occurred in a 33-year-old man
      after a diaphyseal femoral fracture without cranial traumatism. The initial
      examination showed an incomplete picture of coma with tetrapyramidal syndrome and
      cutaneomucous purpura. There was no respiratory damage. We present a magnetic
      resonance spectroscopy analysis of the cerebral lesions observed in the initial
      phase of the embolism, as well as follow-up, which has strengthened the clinical
      and imaging features for the diagnosis.

PMID- 15732116
TI  - Vascular endothelial growth factor gene variability is associated with increased
      risk for AD.
AB  - Converging evidence points to a pivotal role of vascular endothelial growth
      factor (VEGF) in neuronal protection and a lack of its activity in
      neurodegenerative disorders. To investigate this possible association, we
      screened the VEGF gene promoter for various well-known single-nucleotide
      polymorphisms in a series of 249 consecutively recruited Italian patients with
      sporadic Alzheimer's disease (AD). Genetic analysis indicated different
      distributions of two single-nucleotide polymorphisms in the AD population
      compared with healthy control subjects. In particular, the frequencies of 
      2578A/A and -1198C/T genotypes were significantly greater in AD patients than in
      control subjects (23.7 vs 14.7% and 2.8 vs 0%, respectively). The -2578A/A
      genotype was associated with an increased risk for disease, independently of
      apolipoprotein E genotype. The risk was significantly increased with respect to
      various VEGF genotype combinations. In contrast, no difference in serum VEGF
      levels was detected comparing 96 patients and 49 control subjects. These findings
      suggest that polymorphisms within the promoter region of the VEGF gene confer
      greater risk for AD, probably by reducing its neuroprotective effect, and confirm
      the biological role of VEGF in neurodegenerative processes.

PMID- 15732118
TI  - Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6.
AB  - The dominantly inherited spinocerebellar ataxias (SCA) are a clinically and
      genetically heterogeneous group of neurodegenerative disorders characterized by
      progressive gait ataxia, upper limb incoordination, and dysarthria. We studied a
      six-generation kindred of Norwegian ancestry with pure cerebellar ataxia
      inherited in an autosomal dominant pattern. All affected family members had a
      slowly progressive cerebellar ataxia, with an age of onset range from 26 to 60
      years. Brain magnetic resonance imaging study of 11 affected patients showed that
      atrophy was confined to the cerebellum. After excluding all the known SCAs using
      linkage analysis or direct mutation screen, we conducted a genomewide genetic
      linkage scan. With the aid of a novel linkage analysis strategy, we found linkage
      between the disease locus and marker D19S591 and D19S1034. Subsequent genetic and
      clinical analysis identified a critical region of 15.55cM interval on chromosome
      19p13.3, flanked by markers D19S886 and D19S894, and have established a new
      genetic locus designated SCA26. The SCA26 locus is adjacent to the genes for
      Cayman ataxia and SCA6. The region consists of 3.3 million base pairs (Mb) of DNA
      sequences with approximately 100 known and predicted genes. Identification of the
      responsible gene for SCA26 ataxia will provide further insight into mechanisms of
      neurodegeneration.

PMID- 15732117
TI  - Mutant valosin-containing protein causes a novel type of frontotemporal dementia.
AB  - Mutations in the valosin-containing protein (VCP) gene on chromosome 9p13-p12
      recently have been shown to cause autosomal dominant inclusion body myopathy
      associated with Paget's disease of the bone and frontotemporal dementia. Here, we
      report the central nervous system autopsy findings in a 55-year-old German
      patient with inclusion body myopathy and frontotemporal dementia who harbors a
      heterozygous R155C missense mutation residing in the N-terminal CDC48 domain of
      VCP, which is involved in ubiquitin binding. We demonstrate that mutant VCP
      causes a novel type of frontotemporal dementia characterized by neuronal nuclear
      inclusions containing ubiquitin and VCP.

PMID- 15732119
TI  - Alexander disease: combined gene analysis and MRI clarify pathogenesis and extend
      phenotype.

PMID- 15732120
TI  - A mutant PSEN1 causes dementia with Lewy bodies and variant Alzheimer's disease.
AB  - We report early-onset parkinsonism and dementia of 18 years' duration in a 52
      year-old man whose grandfather and father had suffered from a similar
      neurological disease. In this patient, we found neuronal loss in various brain
      regions including the substantia nigra and cerebral cortex, Lewy bodies, cotton
      wool plaques, corticospinal tract degeneration, cerebral amyloid angiopathy, and
      a novel three-base pair deletion in exon 12 of the presenilin-1 (PSEN1) gene. We
      considered that the mutant PSEN1 might play an important role in the pathogenetic
      process of both aggregation of alpha-synuclein into Lewy bodies and deposition of
      beta-amyloid into cotton wool plaques.

PMID- 15732121
TI  - More on repetitive behaviors in Parkinson's disease.

PMID- 15732123
TI  - Subthalamic stimulation activates internal pallidus: evidence from cGMP
      microdialysis in PD patients.
AB  - Parkinson's disease patients benefit from deep brain stimulation (DBS) in
      subthalamic nucleus (STN), but the basis for this effect is still disputed. In
      this intraoperative microdialysis study, we found elevated cGMP extracellular
      concentrations in the internal segment of the globus pallidus, despite negligible
      changes in glutamate levels, during a clinically effective STN-DBS. This supports
      the view that a clinically beneficial effect of STN-DBS is paralleled by an
      augmentation (and not an inactivation) of the STN output onto the GPi.

PMID- 15732124
TI  - Influence of somatosensory input on motor function in patients with chronic
      stroke.

PMID- 15732125
TI  - Bilateral chorea--ballism associated with hyperthyroidism.

PMID- 15732128
TI  - Acute reversible dyskinesia induced by mirtazapine.

PMID- 15732129
TI  - Current controversies: levodopa in the treatment of Parkinson's disease.

PMID- 15732130
TI  - Levodopa in the treatment of Parkinson's disease: current controversies.

PMID- 15732131
TI  - Regenerative and predictive medicine of cardiovascular disease: the 9th Leipziger
      Workshop and the 2nd International Workshop on slide based cytometry.
AB  - Slide-based cytometry (SBC) and related techniques offer unique tools to perform
      complex immunophenotyping, thereby enabling diagnostic procedures at very early
      disease stages. Multicolor or polychromatic analysis of cells by SBC is of
      special importance, not only as a cytomics technology platform but also for
      patients with low blood volume such as neonates. The exact knowledge of the
      location of each cell on the slide allows restaining and subsequent reanalysis of
      the specimen. These separate measurements of the same specimen can be fused to
      one data file (merging), thus increasing the information obtained per cell.
      Relocalization and optical evaluation of the cells, a feature typical of SBC, can
      be of integral importance for cytometric analysis. Due to this feature, artifacts
      can be excluded and morphology of measured cells can be documented. Predictive
      medicine aims at the detection of changes in patient's state before the
      manifestation of the disease or its complications. Such instances concern
      multiorgan failure in sepsis or noninfectious posttraumatic shock in intensive
      care patients or the pretherapeutic identification of high-risk patients
      undergoing cancer cytostatic therapy. Early anti-infectious or antishock therapy
      and curative chemotherapy in combination with stem cell transplantation may
      provide better chances of patients' survival at concomitant cost containment.
      Predictive medicine that guides early individualized decrease or cessation of
      therapy may lower or abrogate potential therapeutic side effects (individualized
      medicine). Regenerative medicine concerns patients who have diseased and injured
      organs and may be treated with transplanted organs. However, there is a severe
      shortage of donor organs that is worsening yearly given the aging population.
      Regenerative medicine and tissue engineering apply the principles of cell
      transplantation, material science, and bioengineering to construct biological
      substitutes that will restore and maintain normal function in diseased and
      injured tissues. Neovascularization is promoted by bone marrow-derived
      endothelial progenitor cells that lead to the formation of entirely new vessels
      into ischemic tissue. With this knowledge, many therapeutical borders can be
      skipped. Diseases formerly uncontrolled can be corrected with stem cells to
      provide causal healing with regeneration processes. The 9th Leipziger Workshop
      combined with the 2nd International Workshop on SBC aimed to offer new methods in
      image cytometry and SBC for solutions in clinical research. It moved toward
      practical applications in clinics and the clinical laboratory. This development
      will be continued in 2005 at the upcoming Leipziger Workshop and the 3rd
      International Workshop on SBC.

PMID- 15732132
TI  - Simultaneous detection of HER2/neu gene amplification and protein overexpression
      in paraffin-embedded breast cancer.
AB  - The determination of HER2/neu status in breast carcinomas has become essential
      for the selection of breast cancer patients for Herceptin therapy. Herceptin
      treatment is used in patients with metastatic breast carcinoma with HER2/neu
      protein overexpression detected by immunohistochemistry (IHC) or gene
      amplification analysed by fluorescence in situ hybridization (FISH). A
      multiparametric fluorescent approach based on the simultaneous detection of
      HER2/neu gene amplification and protein expression was established to increase
      the accuracy, and to improve the reproducibility, of HER2/neu diagnostics. Based
      on four paraffin-embedded breast cancer cell lines, a combined fluorescent
      immunostaining (FIHC) and FISH method was developed by using the PathVysion HER2
      DNA Probe Kit (VYSIS) and the polyclonal antibody from the HercepTest (DAKO).
      Diagnostic applicability was documented on 215 formalin-fixed primary breast
      carcinomas. Criteria for immunofluorescence quantification were chosen by analogy
      with the FDA-approved HercepTest scoring, ranging from 0 to 3+. There was 97.7%
      concordance between conventional IHC and fluorescence IHC. The FISH data
      resulting from the multiparametric approach did not differ from conventional
      FISH. Breast carcinomas with HER2/neu protein overexpression and simultaneous
      gene amplification were detected with 100% sensitivity. In addition, five of the
      215 cases (2.3%) had HER2/neu gene amplification without protein overexpression.
      The main advantage of this novel approach is that polysomy, aneuploidy, gene
      amplification, and protein content can be analysed simultaneously in the same
      cell.

PMID- 15732133
TI  - Protein chip-based microarray profiling of oxidized low density lipoprotein
      treated cells.
AB  - Commercially available high-content Ab380 and extensively validated DLM26
      homemade protein microarrays were used to profile the effects of the pro
      atherogenic molecule, oxidized low density lipoprotein (OxLDL), on human aortic
      smooth muscle cells. Protein microarrays detected 298 proteins in cell lysates
      and 54 of these were differentially regulated. Microarray data were validated by
      immunoblotting for a selected set of up- and down-regulated proteins. The protein
      microarray data sets were compared with our recent cDNA microarray-based gene
      expression results in order to characterize the global effect of OxLDL on smooth
      muscle cell functions. A group of cell-cell interaction molecules was classified
      as up-regulated by OxLDL, whereas nucleic acid/protein biosynthesis, structural
      and humoral response proteins/genes were under-expressed in cells treated by
      OxLDL. These findings reveal the major pattern of OxLDL-induced effects on the
      human aortic smooth muscle cells functions and also demonstrate that protein chip
      based microarrays could be a useful proteomic tool to profile disease-related
      states of muscle cells.

PMID- 15732134
TI  - Large-scale evaluation of quantitative reproducibility and proteome coverage
      using acid cleavable isotope coded affinity tag mass spectrometry for proteomic
      profiling.
AB  - Strategies employing non-gel based methods for quantitative proteomic profiling
      such as isotope coded affinity tags coupled with mass spectrometry (ICAT-MS) are
      gaining attention as alternatives to two-dimensional gel electrophoresis (2-DE).
      We have conducted a large-scale investigation to determine the degree of
      reproducibility and depth of proteome coverage of a typical ICAT-MS experiment by
      measuring protein changes in Escherichia coli treated with triclosan, an
      inhibitor of fatty acid biosynthesis. The entire ICAT-MS experiment was conducted
      on four independent occasions where more than 24 000 peptides were quantitated
      using an ion-trap mass spectrometer. Our results demonstrated that
      quantitatively, the technique provided good reproducibility (median coefficient
      of variation of ratios was 18.6%), and on average identified more than 450 unique
      proteins per experiment. However, the method was strongly biased to detect acidic
      proteins (pI < 7), under-represented small proteins (<10 kDa) and failed to show
      clear superiority over 2-DE methods in monitoring hydrophobic proteins from cell
      lysates.

PMID- 15732135
TI  - Pressure overload and neurohumoral activation differentially affect the
      myocardial proteome.
AB  - Treatment with monocrotaline causes pulmonary hypertension in rats. This results
      in severe pressure overload-induced hypertrophy of the right ventricles, whilst
      the normally loaded left ventricles do not hypertrophy. Both ventricles are
      affected by enhanced neuroendocrine stimulation in this model. We analyzed in
      this model load-induced and catecholamine-induced changes of right and left
      ventricular proteome by two-dimensional gel electrophoresis, tryptic in-gel
      digest, and matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry. All analyzed animals showed right ventricular hypertrophy without
      signs of heart failure. Changes of 27 proteins in the right and 21 proteins in
      the left ventricular myocardium were found. Given the hemodynamic features of
      this animal model, proteome changes restricted to the right ventricle are caused
      by pressure overload. We describe for the first time a potentially novel pathway
      (BRAP2/BRCA1) that is involved in myocardial hypertrophy. Furthermore, we
      demonstrate that increased afterload-induced hypertrophy leads to striking
      changes in the energy metabolism with down-regulation of pyruvate dehydrogenase
      (subunit beta E1), isocitrate dehydrogenase, succinyl coenzyme A ligase, NADH
      dehydrogenase, ubiquinol-cytochrome C reductase, and propionyl coenzyme A
      carboxylase. These changes go in parallel with alterations of the thin filament
      proteome (troponin T, tropomyosin), probably associated with Ca(2+) sensitization
      of the myofilaments. In contrast, neurohumoral stimulation of the left ventricle
      increases the abundance of proteins relevant for energy metabolism. This study
      represents the first in-depth analysis of global proteome alterations in a
      controlled animal model of pressure overload-induced myocardial hypertrophy.

PMID- 15732136
TI  - Microarrays based on affinity-tagged single-chain Fv antibodies: sensitive
      detection of analyte in complex proteomes.
AB  - Protein-based microarrays are among the novel class of rapidly emerging proteomic
      technologies that will allow us to efficiently perform global proteome analysis.
      However, the process of designing adequate protein microarrays is a major
      inherent problem. In this study, we have evaluated a protein microarray platform
      based on nonpurified affinity-tagged single-chain (sc) Fv antibody fragments to
      generate proof-of-principle and to demonstrate the specificity and sensitivity of
      the array design. To this end, we used our human recombinant scFv antibody
      library genetically constructed around one framework, the n-CoDeR library
      containing 2 x 10(10) clones, as a source for our probes. The probes were
      immobilized via engineered C-terminal affinity tags, his- or myc-tags, to either
      Ni(2+)-coated slides or anti-tag antibody coated substrates. The results showed
      that highly functional microarrays were generated and that nonpurified scFvs
      readily could be applied as probes. Specific and sensitive microarrays were
      obtained, providing a limit of detection in the pM to fM range, using
      fluorescence as the mode of detection. Further, the results showed that spotting
      the analyte on top of the arrayed probes, instead of incubating the array with
      large sample volumes (333 pL vs. 40 microL), could reduce the amount of analyte
      required 4000 times, from 1200 attomole to 300 zeptomole. Finally, we showed that
      a highly complex proteome, such as human sera containing several thousand
      different proteins, could be directly fluorescently labeled and successfully
      analyzed without compromising the specificity and sensitivity of the antibody
      microarrays. This is a prerequisite for the design of high-density antibody
      arrays applied in high-throughput proteomics.

PMID- 15732137
TI  - Protein expression patterns in zebrafish skeletal muscle: initial
      characterization and the effects of hypoxic exposure.
AB  - Patterns of protein expression were examined in white skeletal muscle from adult
      zebrafish (Danio rerio). High resolution two-dimensional gel electrophoresis
      resolved between 300 and 400 spots with molecular masses between 20 and 120 kDa
      and isoelectric points between about 5 and 8. Forty spots, representing a range
      of protein size, charge, and abundance were excised, digested with trypsin, and
      subjected to matrix-assisted laser-desorption/ionisation-time of flight mass
      spectrometry for protein identification. Twenty-nine spots were identified,
      including enzymes of energy metabolism, contractile proteins, an iron transport
      protein, and a heat shock protein. In addition, several spots matched theoretical
      proteins predicted from genome sequencing. These theoretical proteins were
      tentatively identified by similarity to known proteins. Patterns of muscle
      protein expression were then measured after zebrafish were exposed to low oxygen
      (16 torr) for 48 h, an exposure previously shown to increase the survival of
      zebrafish at more severe reductions in oxygen. Exposure to low oxygen (hypoxia)
      did not change the general pattern of protein expression but did affect the
      amounts of six low abundance proteins. The relatively subtle effects of hypoxia
      on patterns of muscle protein expression contrasts the widespread changes
      previously documented in mRNA levels in this and other species of fish during
      hypoxic stress. The difference between protein and mRNA expression illustrates
      the need to integrate both measures for a more complete understanding of gene
      expression in fish during hypoxic exposure.

PMID- 15732138
TI  - Normalization and analysis of residual variation in two-dimensional gel
      electrophoresis for quantitative differential proteomics.
AB  - Although two-dimensional gel electrophoresis (2-DE) has long been a favorite
      experimental method to screen proteomes, its reproducibility is seldom analyzed
      with the assistance of quantitative error models. The lack of models of residual
      distributions that can be used to assign likelihood to differential expression
      reflects the difficulty in tackling the combined effect of variability in spot
      intensity and uncertain recognition of the same spot in different gels. In this
      report we have analyzed a series of four triplicate two-dimensional gels of
      chicken embryo heart samples at two distinct development stages to produce such a
      model of residual distribution. In order to achieve this reference error model, a
      nonparametric procedure for consistent spot intensity normalization had to be
      established, and is also reported here. In addition to variability in normalized
      intensity due to various sources, the residual variation between replicates was
      observed to be compounded by failure to identify the spot itself (gel alignment).
      The mixed effect is reflected by variably skewed bimodal density distributions of
      residuals. The extraction of a global error model that accommodated such
      distribution was achieved empirically by machine learning, specifically by
      bootstrapped artificial neural networks. The model described is being used to
      assign confidence values to observed variations in arbitrary 2-DE gels in order
      to quantify the degree of over-expression and under-expression of protein spots.

PMID- 15732139
TI  - Men in (and out of) therapy: central concepts, emerging directions, and remaining
      challenges.
AB  - This article introduces the special issue on recent conceptual, practical, and
      research developments relevant to men and therapy. The paper reviews the
      considerable shifts that have emerged in our understanding and measurement of
      masculinity as it pertains to men's health and therapy. In addition, this
      introduction outlines the primary focus of each article in this special issue and
      describes the general guidelines offered to the contributors. Collectively, these
      special-issue articles describe promising paradigms, provide useful examples, and
      stress the need for further research on men, masculinity, and the therapeutic
      process.

PMID- 15732140
TI  - CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and
      adenocarcinoma of the stomach.
AB  - CDX2 and liver-intestine (LI)-cadherin are intestine-specific markers and both
      are physiologically expressed in the small intestine and colon. Recent studies
      have demonstrated that CDX2 regulates LI-cadherin gene (CDH17) expression in
      colorectal cancer. The present study investigated the relationship of CDX2 and LI
      cadherin expression in gastric cancer. One hundred and nine pairs of tumour and
      non-cancerous gastric mucosa were collected from gastrectomy specimens. Protein
      expression levels of CDX2 and LI-cadherin were determined by immunohistochemical
      staining. Semi-quantitative RT-PCR showed that the mRNAs of both CDX2 and CDH17
      were highly expressed in tumour compared with non-cancerous mucosa.
      Overexpression of CDX2 was significantly associated with CDH17 in gastric
      adenocarcinoma. Furthermore, the expression of CDX2 and LI-cadherin proteins was
      strongly coupled in intestinal metaplasia. In conclusion, overexpression of CDH17
      is significantly associated with CDX2.

PMID- 15732142
TI  - Pfizer: Celebrex increases heart attack risk.

PMID- 15732141
TI  - Differential expression of activation-induced cytidine deaminase (AID) in nodular
      lymphocyte-predominant and classical Hodgkin lymphoma.
AB  - Activation-induced cytidine deaminase (AID) is indispensable for class switch
      recombination and somatic hypermutation of immunoglobulin genes. Expression of
      AID has been detected in germinal centre centroblasts and in lymphomas derived
      from germinal centre cells. However, in situ studies of AID expression have until
      now been hampered by a lack of antibodies suitable for immunohistochemistry. To
      overcome this problem, an AID-specific monoclonal antibody suitable for
      immunohistochemical staining of formalin-fixed, paraffin wax-embedded tissue
      sections has been generated. This antibody was shown to detect AID expression in
      normal germinal centre B-cells as well as in non-Hodgkin lymphomas with a
      putative germinal centre origin. Using this antibody, a virtually exclusive
      cytoplasmic localization of AID in normal and neoplastic B-cells is shown.
      Employing a combination of immunohistochemistry and AID-specific in situ
      hybridization, it is demonstrated that AID is consistently expressed in the
      neoplastic cells of nodular lymphocyte-predominant Hodgkin lymphoma (HLnlp) but
      only infrequently in classical HL (cHL). This is in keeping with the notion that
      tumour cells of HLnlp represent transformed germinal centre B-cells showing
      evidence of somatic hypermutation. AID represents an additional marker useful in
      the differential diagnosis of HLnlp and cHL.

PMID- 15732143
TI  - Heart failure a risk after noncardiac surgery.

PMID- 15732144
TI  - Improving quality of life in early Parkinson's.

PMID- 15732146
TI  - Hard work help heal hip fractures. Extended-care treatment allows more people to
      recover better, but who pays the freight?

PMID- 15732145
TI  - Cell phone use raises cancer risk. Swedish researchers demonstrate the first
      small link between cell phones and tumors, but is it time to panic?

PMID- 15732147
TI  - Acupuncture helpful for knee pain.

PMID- 15732148
TI  - Vitamin D for bad knees.

PMID- 15732149
TI  - Weather changes really can make your bones ache.

PMID- 15732150
TI  - Attitude influences how you age. If you're upbeat, you're likely to resist
      frailty, and, if people treat you as a competent adult, you're likely to be one.

PMID- 15732151
TI  - Technology eases living with heart failure. New implantable devices, stem cell
      therapy, and monitoring techniques may improve length and quality of life.

PMID- 15732152
TI  - New surgery for aortic aneurysm is safer than traditional approach. But over the
      long haul, the traditional technique may prove to be more stable.

PMID- 15732153
TI  - Which oral drug is right for your type 2 diabetes? New thinking on oral drug
      combinations that can provide better glycemic control.

PMID- 15732154
TI  - Minimizing surgery in skin cancer treatment. A new test looks for cancer in the
      lymph nodes during melanoma surgery, while a topical cream helps people with
      another form of skin cancer avoid the knife.

PMID- 15732155
TI  - St. John's wort reduces effectiveness of anticancer medication.

PMID- 15732156
TI  - Too few older US adults screened for colon cancer.

PMID- 15732157
TI  - Getting the most from exercising only on weekends. Daily exercise is best, but if
      you're healthy and have just weekends to stay fit, here's what you need to know.

PMID- 15732158
TI  - Large doses of supplements can damage your eyes.

PMID- 15732159
TI  - Coffee linked to increased levels of heart risk markers.

PMID- 15732160
TI  - Sustained exercise prevents heart failure.

PMID- 15732161
TI  - I have blood clots in my leg veins and have been put on a blood-thinner pill.
      Even though I took my medication, a clot still broke off and went to my lung.
      What should I do now?

PMID- 15732162
TI  - I've begun to see more "floaters," or small specks, in front of my eyes. Is this
      something I should worry about?

PMID- 15732163
TI  - My big toe has been extremely painful for some time. I thought it was a bunion,
      but I've been told I have gout. I thought gout was something only overweight men
      developed. What is it?

PMID- 15732165
TI  - Diverticular disease. The importance of getting enough fiber.

PMID- 15732164
TI  - [A technique of nasal and nasopharyngeal lavage in acute inflammatory diseases].

PMID- 15732166
TI  - Health tips. Altitude illness.

PMID- 15732167
TI  - Cardiac rehabilitation after heart attack improves survival.

PMID- 15732168
TI  - A combination treatment for localized prostate cancer.

PMID- 15732169
TI  - Fatigue. A cue to rest, or a sign of something more?

PMID- 15732170
TI  - Advance directives. A plan for end of life.

PMID- 15732171
TI  - Bunions. From shoe selection to surgery.

PMID- 15732172
TI  - Are certain types of chocolate healthier than others?

PMID- 15732173
TI  - I'm about to have elective surgery. My doctor recommended that I start taking a
      drug called metoprolol a few days before surgery to protect my heart. How does
      this work?

PMID- 15732174
TI  - Beyond menopause. Life after estrogen.

PMID- 15732175
TI  - Organizing pathology: European and American approaches to medical museology in
      the nineteenth century.

PMID- 15732176
TI  - Dipyridamole for renal phosphate leak in successfully renal transplanted
      hypophosphatemic patients.
AB  - AIM AND BACKGROUND: Hyphosphatemia can be seen in renal transplant recipients.
      Hyperparathyroidism, glucocorticoid treatment, renal denervation and impairment
      of renal tubular phosphate reabsorption are the most common causes of
      hyphosphatemia in these patients. It is well-known that dipyridamole enhances
      renal tubular phosphate reabsorption in some clinical conditions. We did not find
      any information about the effect of dipyridamole in renal transplant recipients
      (RTRs) with hypophosphatemia. For this reason, we decided to give dipyridamole 11
      RTRs with hypophosphatemia. PATIENTS AND METHODS: Eleven RTRs whose serum
      phosphate and creatinine levels were below 2.5 mg/dl and 2 mg/dl, respectively,
      were included in this study. None of the patients received drugs altering
      phosphate metabolism and they did not change their routine diets. Urinary
      phosphate excretion and tubular phosphate reabsorption (TPR) were calculated
      before and 3 weeks after dipyridamole treatment. RESULTS: The mean levels of
      serum-urine (daily) phosphate and TPR before dipyridamole treatment were 1.94 +/-
      0.46 mg/dl, 7,187.5 +/- 1,833.49 mg/day and -2.78 +/- 0.62, respectively. After
      treatment, the mean levels of serum-urine phosphate and TPR were 2.73 +/- 0.46
      mg/dl, 4,845.27 +/- 1,138.99 mg/day and -1.48 +/- 0.80, respectively. Serum and
      urine phosphate levels and TPR were found to be significantly different before
      and after dipyridamole therapy (p < 0.05). CONCLUSION: Short-term dipyridamole
      therapy increased TPR and serum phosphate levels and decreased urinary phosphate
      excretion. We did not observe negative effect on renal functions in these cases.
      Although the number of the cases included in this study is small, dipyridamole is
      an effective choice in management of hypophosphatemic RTRs.

PMID- 15732177
TI  - Arctic climate: the heat is on.

PMID- 15732178
TI  - Neurocognitive changes: where's the meat?

PMID- 15732179
TI  - Parity in mental health coverage: the goal of equal access to mental health
      treatment under the Mental Health Parity Act of 1996 and the Mental Health
      Equitable Treatment Act of 2001.

PMID- 15732180
TI  - The search for a cure: combating the problem of conflicts of interest that
      currently plagues biomedical research.

PMID- 15732181
TI  - Recommended response for human cloning patent applications.

PMID- 15732182
TI  - Informed consent: should it be extended to vaccinations?

PMID- 15732183
TI  - The fetal homicide fallacy: a comparison of California's inconsistent statutes to
      other states.

PMID- 15732185
TI  - Appearances.

PMID- 15732184
TI  - [Guidelines for ambulatory monitoring of kidney transplant patients. Adaptation
      of the Guidelines of the American Society of Transplantation (J Am Soc Nephrol
      2000; 11 (S1): 86)].

PMID- 15732186
TI  - The doctrine of informed consent: to inform or not to inform?

PMID- 15732188
TI  - Practical ethics. Scrap the nurses' book?

PMID- 15732187
TI  - Fitting a square peg into a round hole?: imposing informed consent and post-trial
      obligations on United States sponsored clinical trials in developing countries.

PMID- 15732189
TI  - It's my body, it's my choice: the Partial-Birth Abortion Ban Act of 2003.

PMID- 15732190
TI  - Human rights and fair access to medication.

PMID- 15732191
TI  - Variation in the human TP53 gene affects old age survival and cancer mortality.
AB  - Longevity may depend on a balance between tumor suppression and tissue renewal
      mechanisms [Campisi, J., 2003. Cancer and ageing: rival demons? Nat. Rev. Cancer
      3 (5), 339-349]. Mice with constitutively activated p53 are almost cancer free
      but their life span is reduced and accompanied by early tissue atrophy [Tyner et
      al., 2002. p53 mutant mice that display early ageing-associated phenotypes.
      Nature 415 (6867) 45-53]. Replacement of arginine (Arg) by proline (Pro) at
      position 72 of human p53 decreases its apoptotic potential [Dumont et al., 2003.
      The codon 72 polymorphic variants of p53 have markedly different apoptotic
      potential. Nat. Genet. 33 (3), 357-365] providing a tool to test for a similar
      trade-off in humans. Using a formal meta-analysis of the published literature we
      show that carriers of the TP53 codon 72 Pro/Pro genotype have an increased cancer
      risk compared to Arg/Arg carriers (p<0.05). Next, in a prospective study of 1226
      people aged 85 years and over we show that carriers of the Pro/Pro genotype have
      a 41% increased survival (p = 0.032) despite a 2.54 fold increased (p = 0.007)
      proportional mortality from cancer. It is suggested that human p53 protect
      against cancer but at a cost of longevity.

PMID- 15732193
TI  - Comprehensive two-dimensional gas chromatography--a powerful and versatile
      technique.
AB  - Comprehensive two-dimensional gas chromatography (GC x GC) was introduced about a
      decade ago and is, today, rapidly become a powerful and widely applicable
      technique for the characterisation and analysis of a variety of complex samples.
      GC x GC provides structurally ordered chromatograms in the 2D plane, and features
      an impressive peak capacity. Combining GC x GC and time-of-flight mass
      spectrometry (ToFMS), with its fast acquisition rates and excellent deconvolution
      potential, has been an important step forward which enables identification and
      identity confirmation of large numbers of target analytes and unknowns in one
      run. Up until now, some 150 papers have been published, fish and food,
      environmental and air analysis. Polyhalogenated aromatics and other priority
      pollutants, flavours and fragrances, fatty acid methyl esters and essential oils,
      are among the classes of compounds which frequently receive attention. In
      summary, GC x GC is increasingly being recognised as the separation technique of
      choice in problem areas.

PMID- 15732192
TI  - Predictors of mortality: an international comparison of socio-demographic and
      health characteristics from six longitudinal studies on aging: the CLESA project.
AB  - PURPOSE: Multiple factors contribute to mortality in the elderly, but the extent
      to which traditional factors contribute independently to mortality in different
      countries is not known. Our objective is to determine the differential impact of
      socio-demographic variables, selected diseases, health habits and disability on
      all-cause mortality, among older people living in five European countries and
      Israel. METHODS: From six longitudinal studies on aging (TamELSA-Tampere
      (Finland), CALAS-Israel, ILSA-Italy, LASA-Netherlands, AL-Leganes (Spain), SATSA
      Sweden), a harmonized common database was created in the context of the CLESA
      Project (Cross-national determinants of quality of life and health services for
      the elderly). A common five-year follow-up was used. RESULTS: The highest
      mortality rate was found in Tampere among females (98.7%) and in Israel among
      males (108.3%), whereas the lowest was observed in Leganes for males (72.3%) and
      in The Netherlands for females (44.6%). In multivariate models, some predictors
      were homogeneously, significantly distributed across the six countries, including
      older age (HR = 1.57) and male sex (HR = 1.60) among the socio-demographic
      variables; smoking status (HR = 1.15) and alcohol consumption (HR = 0.81) among
      the health habits variables; presence of heart disease (HR = 1.34), diabetes (HR
      = 1.46), cancer (HR = 1.93), respiratory disease (HR = 1.19), and disability (HR
      = 2.92) among the health status variables. Marital status, education, and drug
      use did not have homogeneous effects in the six countries. DISCUSSION: This large
      international study shows that multiple factors contribute to increased risk of
      all cause mortality among older people and that most risk factors are similar
      across countries. Disability, age greater than 80 years, cancer and male sex were
      identified as the strongest common risk factors of mortality.

PMID- 15732194
TI  - Why focus on the dose and schedule of chemotherapy?

PMID- 15732195
TI  - Accommodation at work: lessons from the Americans with Disabilities Act and
      possibilities for alleviating the American worker time crunch.

PMID- 15732196
TI  - [N. V. Sklifosovskii (on 100th anniversary of his death)].

PMID- 15732197
TI  - Medicare program; durable medical equipment regional carrier service areas and
      related matters. Final rule.
AB  - This final rule provides a mechanism for us to expeditiously make changes to the
      durable medical equipment regional carrier (DMERC) service area boundaries
      without notice and comment rulemaking. Through this mechanism, we can change the
      geographical boundaries served by the regional contractors that process durable
      medical equipment claims through issuance of a Federal Register notice and make
      other minor changes in the contract administration of the DMERCs. The mechanism
      provides a method for increasing or decreasing the number of DMERCs, changing the
      boundaries of DMERCs based on criteria other than the boundaries of the Common
      Working File sectors, and awarding new contractors to perform statistical
      analysis or maintain the national supplier clearinghouse. We will publish these
      changes and their justifications in a Federal Register notice, rather than
      through notice and comment rulemaking. Although we may change the number and
      configuration of regional carriers, we are not altering the criteria and factors
      that we use in awarding contracts. Through this final rule, we are improving the
      contracting process so that we can swiftly meet the challenges of the changing
      healthcare industry and address the changing needs of beneficiaries, suppliers,
      and the Medicare program.

PMID- 15732198
TI  - The right to privacy of medical records: balancing competing expectations.

PMID- 15732199
TI  - Cloning people: a Jewish law analysis of the issues.

PMID- 15732200
TI  - Choice, tradition, and the new genetics: the fragmentation of the ideology of
      family.

PMID- 15732201
TI  - The use of placebos in clinical trials: responsible research or unethical
      practice?

PMID- 15732202
TI  - Who's watching the watchdogs? Responding to the erosion of research ethics by
      enforcing promises.
AB  - For more than thirty years, federal regulations--collectively known as the
      "Common Rule"--have governed all federally funded medical research involving
      human subjects. The Common Rule requires, inter alia, that any research facility
      receiving federal funds submit a Federal Wide Assurance (FWA) to the department
      or agency from which funding is sought. The FWA is a contract in which the
      research facility promises to abide by the Common Rule for all its research that
      involves human subjects, whether it is privately or federally funded. Drawing
      upon other instances in which third-party beneficiaries have successfully
      enforced government contracts, this Note argues that, upon discovery that a
      contract of assurance has been breached in the course of federally or privately
      funded research, a research subject should be able to maintain an action against
      the research institution as a third-party beneficiary to that contract.

PMID- 15732203
TI  - I-DNA-fication, personal privacy, and social justice.

PMID- 15732204
TI  - Purposive interpretation and the march of genetic technology.

PMID- 15732205
TI  - The patentability of human-animal chimeras.

PMID- 15732206
TI  - In good conscience: the legal trend to include prescription contraceptives in
      employer insurance plans and Catholic charities' "conscience clause" objection.

PMID- 15732207
TI  - Genotype discrimination: the complex case for some legislative protection.

PMID- 15732208
TI  - Second thoughts: how human cloning can promote human dignity.

PMID- 15732209
TI  - An equality paradigm for preventing genetic discrimination.

PMID- 15732210
TI  - Stretching the limits of "rights talk": securing health care entitlements for
      children.
AB  - Health care rights by their very nature have to be considered not only in a
      traditional legal context structured around the ideas of human autonomy but in a
      new analytical framework based on the notion of human interdependence. "A healthy
      life depends upon [social] interdependence: the quality of air, water, and
      sanitation which the [state] maintains for the public good; the quality of one's
      caring relationships, which are highly correlated to health; [as well as] the
      quality of health care and support furnished officially by medical institutions
      and provided informally by family, friends, [and the community]."

PMID- 15732211
TI  - Infected judgment: legal responses to physician bias.

PMID- 15732212
TI  - Researcher liability for negligence in human subject research: informed consent
      and researcher malpractice actions.
AB  - Two sets of federal regulations, the "Common Rule" and Food and Drug
      Administration (FDA) regulations, govern human subject research that is either
      federally-funded or involves FDA regulated products. These regulations require,
      inter alia, that: (1) researchers obtain informed consent from human subjects,
      and (2) that an Institutional Review Board (IRB) independently review and approve
      the research protocol. Although the federal regulations do not provide an express
      cause of action against researchers, research subjects should be able to bring
      informed consent and malpractice actions against researchers by establishing a
      duty of care and standard of care. Researchers owe human subjects a duty of care
      analogous to the special relationship between physicians and patients. The
      federal regulations should provide the minimum standard of care for informed
      consent in human subject research, and complying with them should be a partial
      defense. In contrast, expert testimony should establish the standard of care for
      researcher malpractice, and IRB approval should be a partial defense.

PMID- 15732213
TI  - Attention deficit disorder. Condition requiring "chronic disease" management
      strategies.

PMID- 15732214
TI  - Another approach to managing depression.

PMID- 15732215
TI  - New family practice residency program.

PMID- 15732216
TI  - Family practice websites.

PMID- 15732217
TI  - Letter from Mexico. Mexico's health care system.

PMID- 15732218
TI  - Screening for fetal alcohol spectrum disorder.
AB  - QUESTION: I have several patients whom I suspect are drinking during pregnancy.
      How can I find out for sure if they are? ANSWER: You can use one of the validated
      tools to screen for problem drinking. Motherisk uses the TWEAK test, but others
      are just as good. Following birth, you can test infants' meconium for metabolites
      of ethanol to detect whether they were exposed in utero to excessive drinking.

PMID- 15732219
TI  - Dermacase. Rheumatoid nodules.

PMID- 15732220
TI  - Doctor-patient communication: complaints and legal actions.

PMID- 15732221
TI  - Lose weight to lose erectile dysfunction.

PMID- 15732222
TI  - Attention deficit disorder in adults. Management in primary care.
AB  - OBJECTIVE: To review the ways attention deficit disorder (ADD) presents in adults
      in primary care and to suggest treatment approaches. SOURCES OF INFORMATION:
      PsycINFO, PubMed, and Academic Search Elite databases were searched. Level I
      evidence supports the effectiveness of stimulants for treating ADD in adults, and
      mixed evidence (levels I and II) supports the effectiveness of antidepressants.
      MAIN MESSAGE: Attention deficit disorder is a prevalent but often unrecognized
      disorder in adults. The diagnosis, which must include onset of symptoms before
      age 7, is often missed. This could be because family physicians are not always
      familiar with the presentation in adults, because it frequently presents with
      comorbid problems, or because specific questions are not asked to elicit the
      diagnosis. Diagnosis is based on clinical assessment often assisted by self
      rating scales. Management includes support and education, helping patients
      develop additional structure in their lives and make necessary behavioural
      changes, enhancing self-esteem, supporting and educating families, and
      prescribing medication. Medication choices include stimulants and
      antidepressants; medication can benefit up to 60% of people with ADD. CONCLUSION:
      It is crucial for primary care physicians to identify ADD in adults and to
      initiate treatment or referral. Several simple interventions can be employed.

PMID- 15732223
TI  - Predictive value of a history of varicella infection.
AB  - OBJECTIVE: To determine whether a history of previous varicella infection
      provides a reliable marker for prior infection. QUALITY OF EVIDENCE: MEDLINE was
      searched from January 1996 to May 2002 using the MeSH headings "varicella,"
      "chickenpox" and "medical history taking." Recommendations in this paper are
      based on evidence from well designed cross-sectional studies. MAIN MESSAGE:
      Serologic testing is advised, rather than presumptive vaccination, for those with
      a negative or uncertain history of varicella; most will be immune. For those with
      a positive history of varicella, the advice given depends on the population. For
      populations at higher risk of varicella infection (eg, health care workers,
      pregnant women), routine serum testing is recommended. For low-risk populations,
      physicians could accept a positive history of varicella as a reliable indicator
      of immunity. CONCLUSION: Most studies found that patients' history of varicella
      had a high positive predictive value and a low negative predictive value. These
      findings suggest that a positive history of varicella is a reliable marker of
      disease while a negative history does not not predict lack of immunity.

PMID- 15732224
TI  - Family medicine obstetrics. Collaborative interdisciplinary program for a
      declining resource.
AB  - PROBLEM BEING ADDRESSED: A continuing decline in the number of family physicians
      in Canada providing obstetric, and particularly intrapartum, care. OBJECTIVE OF
      PROGRAM: The Maternity Centre of Hamilton in Ontario was a pilot project
      initiated to help family physicians provide full obstetric care through a
      collaborative interdisciplinary model and shared call. PROGRAM DESCRIPTION:
      Eleven family physicians provided care in collaboration with a nurse practitioner
      and other health professionals. Women came from the Maternity Centre's own
      practices, community physicians, or agencies, or through self-referral. More than
      a quarter of the women were considered psychosocially high-risk patients. Key
      features of the program included interdisciplinary collaboration and information
      technology that supported prenatal and birth documentation. CONCLUSION: The
      program has helped family physicians, and even recruited some, to practise full
      obstetric care and has provided high-quality, accessible services to pregnant
      women. Physicians experienced increased jab and personal satisfaction, and
      patients were highly satisfied with the service.

PMID- 15732225
TI  - When things go wrong.

PMID- 15732226
TI  - Lung cancer in Ireland.

PMID- 15732227
TI  - Lung cancer audit in an Irish teaching hospital.
AB  - BACKGROUND: Lung cancer is the most common cause of cancer-related death in
      Ireland. There are few complete data sets available as to the stage and cell type
      of lung cancers at time of presentation in Ireland. AIM: To audit the lung
      cancers presenting to a large Dublin teaching hospital over a 12-month period.
      METHOD: Prospective evaluation of all lung tumours presenting to our institution
      over a consecutive 12-month period. RESULTS: One hundred and ninety-eight lung
      cancers presented over the study period. There were 34 cases of small cell
      carcinoma and 150 cases of non-small cell carcinoma (NSCC). Fourteen patients
      were too ill or compromised at time of presentation for tissue confirmation. The
      most common cell type was squamous carcinoma. Eighty-four per cent of the NSCCs
      were either stage 3 or 4 at presentation. CONCLUSION: Most lung cancers present
      late in the time course of the disease. Distribution of cell type and location
      are similar in Ireland and other developed countries.

PMID- 15732228
TI  - Weight gain after laparoscopic cholecystectomy.
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LC) relieves symptomatic
      cholelithiasis (SC) but may facilitate postoperative gluttony. AIM: To examine
      changes in body mass index (BMI) and general health of a cohort of patients three
      years after uncomplicated LC for SC. METHODS: Patients were studied three years
      after uncomplicated LC and compared to age- and gender-matched controls who had
      undergone non-biliary surgery. RESULTS: Forty-two patients and 42 controls were
      studied. The mean age of the patients was 55 years (range 29-82) versus 54 years
      (25-82) for controls. Patients undergoing LC increased their mean BMI by 1.8
      kg/m2. Females were particularly likely to gain weight (mean change in BMI=+2.1),
      with no significant difference being found between premenopausal and
      postmenopausal women. Of the 24 LC patients who claimed to continue their low fat
      diet, the mean BMI changed from 27.6 to 29.6 kg/m2. The mean BMI of the 17 people
      who claimed regular exercise changed less markedly (+1.4) than those who admitted
      infrequent exercise (+2.1). CONCLUSION: Selection for LC may identify patients at
      risk of continuing or resumed aetiological contributors to obesity. Follow-up
      long after the surgery may therefore be necessary to facilitate additional
      healthcare interventions.

PMID- 15732229
TI  - Sonovue improves endocardial border detection and variability in assessing wall
      motion score and ejection fraction during stress echocardiography.
AB  - BACKGROUND: Stress echocardiography is useful for assessing patients with
      coronary artery disease unable to undergo formal exercise testing. Considerable
      skill is required to avoid large intra- and inter-observer variability due to
      poor endocardial definition. Intravenous ultrasound contrast agents are now
      available which may improve this variability. AIM: To study intravenous Sonovue
      in assessing wall motion score and ejection fraction (EF) during stress
      echocardiography. METHODS: Thirty-eight patients undergoing arbutamine stress
      echocardiography for known or suspected coronary artery disease were studied.
      Echocardiographic analysis of wall motion score index, endocardial border
      detection (EBD) and EF was performed at rest and at peak stress before and after
      intravenous injection of Sonovue, by experienced and inexperienced observers.
      RESULTS: All three observers noted an improvement in endocardial border
      definition following Sonovue (p=<0.001). At baseline, there was a significant
      difference in wall motion score index between experienced and inexperienced
      observers at rest (p=0.01) and at peak stress (p=0.001). Following Sonovue
      administration this was no longer significant (p=0.07, p=0.114). Intra-observer
      variability of end diastolic, end systolic volumes (ESV) and EF improved
      following contrast (p<0.05) at rest and during stress. CONCLUSION: Sonovue
      significantly improved EBD and reduced intra-observer variability of EF at rest
      and during peak arbutamine infusion.

PMID- 15732230
TI  - One-stage Fowler-Stephens orchidopexy for impalpable undescended testis.
AB  - BACKGROUND: The Fowler-Stephens orchidopexy (FSO) is a well-described treatment
      for high maldescended testes where the limiting factor for successful placement
      in the scrotum is short testicular vessels. The operation involves division of
      these vessels. The testicular blood supply is then dependent on collaterals from
      the vasal artery. AIMS: To assess the long-term outcome of patients who underwent
      this procedure in our institution. METHODS: The medical records of 20 patients
      who underwent 22 FSO from 1978 to 1999 by one urologist (HB) were reviewed.
      Outcome was assessed in terms of testicular position and size. RESULTS: Age at
      operation ranged from 2 to 14 years (mean 5.8 years). All patients had a one
      stage FSO and in two of them the procedure was bilateral. In five patients, FSO
      was preceded by a diagnostic laparoscopy. Mean follow up was 22 months (range 0
      121 months). Overall, results were considered good in 18 of 22 testes (82%).
      CONCLUSION: Our results for the one-stage FSO are comparable with other
      procedures for the management of high maldescended testis.

PMID- 15732231
TI  - Current management of corticosteroid-induced osteoporosis: variations in
      awareness and management.
AB  - BACKGROUND: Guidelines for the prevention of corticosteroid-induced osteoporosis
      (CIO) have been widely published. There are no guidelines on the use of gastro
      protectants with corticosteroids (CS). AIMS: To determine whether patients
      receiving CS therapy are evaluated and treated for osteoporosis risk, how
      management varied by steroid dose and diagnosis, and how many patients received
      gastro-protection. METHODS: A retrospective audit of 4,350 patients presenting to
      four medical specialities. RESULTS: One hundred and fifty-one patients prescribed
      CS were identified. Indications for CS therapy included renal transplantation
      (32%) and asthma/respiratory diseases (23%), inflammatory arthritis/vasculitis
      (32%) and inflammatory bowel disease/auto-immune hepatitis/other (13%). Risk of
      osteoporosis was mentioned in 13% of charts. The prescription rates for bone
      protection agents varied from 69% to 4% according to the medical speciality
      attended. Gastro-protectants were prescribed for 44% of patients. CONCLUSION:
      There are large variations among medical specialties both in the prescription of
      gastro-protectant agents and in the use of measures to prevent CIO. Simpler
      guidelines could facilitate rational prescribing in these patients.

PMID- 15732232
TI  - Should patients with a pre-operative prostate-specific antigen greater than 15
      ng/ml be offered radical prostatectomy?
AB  - BACKGROUND: Patients with prostate cancer with a pre-operative prostate-specific
      antigen (PSA) >15 ng/ml who undergo radical retropubic prostatectomy (RRP)
      generally do not have a good outcome, yet may have organ-confined cancer and
      should be offered the option of surgery. AIM: To assess the outcome of patients
      who underwent RRP with a pre-operative PSA >15 ng/ml. METHODS: Thirty-four
      patients, mean pre-operative PSA: 25.46 ng/ml (15.03-76.6) and mean Gleason
      score: 6.4 (5-9) were assessed. RESULTS: Two groups were identified. Group I: 41%
      (14/34) have no biochemical recurrence to mean follow up of 58 months (30-106).
      Mean PSA: 18.8 ng/ml (15.03-25.84). Mean Gleason score: 6.1 (5-7). Clinical
      stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement.
      Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease
      to mean follow up of 66 months (36-98). Mean PSA: 28.9 ng/ml (15.28-76.6). Mean
      Gleason score: 6.7 (5-9). Clinical stage: T1c in 25%. Eleven patients had seminal
      vesicle (8) involvement or positive lymph nodes (3) or both (2). CONCLUSION: RRP
      seems feasible in patients whose pre-operative PSA is between 15 and 25 ng/ml
      with stage T1c, Gleason score < or = 7 and negative lymph node frozen section.

PMID- 15732233
TI  - Thyroid function in haemochromatosis.
AB  - BACKGROUND: In hereditary haemochromatosis (HH), the thyroid gland is the site of
      substantial iron deposition. However, there have been relatively few reported
      cases of thyroid dysfunction in HH. AIM: To evaluate the prevalence of thyroid
      disorders in a large group of patients with HH. METHODS: A variety of endocrine
      investigations were undertaken including thyroid function tests and thyroid
      antibody studies. RESULTS: A total of 154 consecutive patients (123 male, 31
      female) were studied. One case of primary hypothyroidism was identified, giving a
      prevalence of 0.6%. Subclinical hypothyroidism was identified in two females,
      giving a prevalence of 1.3%. Iatrogenic hypothyroidism was identified in two
      other cases. No case of hyperthyroidism was identified. CONCLUSION: Thyroid
      dysfunction is an uncommon occurrence in patients with HH.

PMID- 15732234
TI  - Undergraduate medical students' experience in general practice.
AB  - BACKGROUND: Increasingly, undergraduate medical education is becoming community
      based. Logbooks are a useful tool in documenting the range of clinical exposure
      and learning opportunities available to students during clinical training,
      particularly where the role of new clinical settings for training medical
      students is being explored. AIMS: To describe the clinical experience of medical
      students during an undergraduate programme in general practice at an Irish
      University. METHODS: Medical students in the fifth year of medical school were
      asked to record data from 20 consecutive consultations during a clinical
      attachment in general practice. RESULTS: A total of 186 students (82% of total)
      recorded data on 3,710 consultations. The patient population encountered was
      similar in demography and morbidity profile to other general practice
      populations, with hypertension, preventive immunisation and cough the most
      frequently encountered diagnostic labels. Respiratory illness and circulatory
      illness were the most frequently encountered primary and secondary presentations,
      respectively. An active role was adopted by students in almost half of all
      consultations. CONCLUSIONS: This paper provides evidence that general practice in
      Ireland is a setting in which medical students can both encounter a wide range of
      clinical problems and engage in active learning processes.

PMID- 15732235
TI  - Naltrexone for alcohol-dependent patients.
AB  - BACKGROUND: Clinical trials have shown that naltrexone 50 mg/day reduces alcohol
      consumption and relapse rates in alcohol dependents. AIM: To investigate the
      efficacy of 50mg/day dose of naltrexone in the maintenance of alcohol-dependent
      subjects over a 36-week treatment period. METHODS: Subjects were randomised into
      two equal groups, consisting of 116 male alcohol-dependent patients who met the
      DSM-IV criteria for alcohol dependence and were seeking treatment. The
      participants received naltrexone or placebo at a dose of 50 mg/day and were
      treated in an outpatient clinic, offering a weekly 0.5-hour individual
      counselling session. Days retained in treatment were measured. RESULTS: Forty-one
      participants (35.3%) completed the 36-week study. Completion rates by group were
      44.8% for the 50 mg naltrexone group and 25.9% for the placebo group (chi2=4.56,
      DF=1, 2-sided significance=0.033). CONCLUSION: The results support the efficacy
      and safety of naltrexone for outpatient treatment of alcohol-dependent
      individuals in Iran.

PMID- 15732237
TI  - The Academy's foray into the politics of phthisis (tuberculosis) 1940-1946.

PMID- 15732236
TI  - Giant colonic diverticulum.
AB  - BACKGROUND: Over 100 giant colonic diverticuli have been recorded in the
      literature to date. The magnetic resonance imaging (MRI) and pathophysiology of
      their aetiology have rarely been described. AIM: To report a giant colonic
      diverticulum along with the MRI of this clinical entity. RESULTS: An 87 year old
      female presented with symptoms of tenesmus, urgency and alteration in bowel
      habit. A type I giant colonic diverticulum was diagnosed and a segmental colonic
      surgical resection was performed. The plain abdominal radiograph, barium enema
      and MRI, along with classification and management options are presented.
      CONCLUSION: Giant colonic diverticuli are rare surgical curiosities that may be
      successfully treated with either primary segmental or extended colonic resection.

PMID- 15732238
TI  - Mental illness in 19th-century Ireland: a qualitative study of workhouse records.

PMID- 15732239
TI  - Stroke and limb ischaemia in hepatitis C virus-related cryoglobulinaemia.

PMID- 15732240
TI  - An ominous inguinal hernia.

PMID- 15732241
TI  - Non-culturable Haemophilus influenzae meningitis identified by 16S rDNA PCR and
      sequencing.

PMID- 15732242
TI  - [Annual meeting of the Austrian Obesity Society].

PMID- 15732243
TI  - [The adipose tissue as an endocrine organ].
AB  - The adipose tissue stores excess energy but also produces a series of substances
      including cytokines (adipocytokines) which participate in regulatory processes.
      The physiologic and pathophysiologic relevance of these factors has only recently
      been described in more detail. Defects in adiponectin as well as overproduction
      of free fatty acids play an important role in the development of insulin
      resistance typical for obesity. Rare forms of obesity or lipodystrophy can now be
      explained by defects in the leptin system. The contribution of adipose tissue and
      its cytokines to the relationship between inflammation and the metabolic syndrome
      is currently under investigation.

PMID- 15732244
TI  - [Endocrinologie and obesity].
AB  - The endocrine system plays a central role in the regulation of body weight and
      fat distribution. The influence of thyroid hormones, growth hormone, cortisol und
      sex steroids on body weight are described with a focus on hyper- and hypofunction
      of these systems. In addition, sequelae of therapeutic interventions aiming to
      restore homeostasis in dysfunction are discussed. Finally, neuroendocrine control
      of appetite and syndromes that are consequences of disturbed neuroendocrine
      control of food intake are described.

PMID- 15732245
TI  - [Mitochondrial function--role in insulin resistance and lipid metabolism].
AB  - Risk factors for the development of type 2 diabetes mellitus, including weight
      gain, lack of physical exercise and increasing age, are associated with an
      impaired mitochondrial function. Clinical studies could demonstrate a reduced
      mitochondrial activity in non-diabetic but insulin-resistant offsprings of type 2
      diabetics. A key enzyme in the regulation of cellular energy supply and thus also
      in glucose and lipid metabolism is AMP-activated proteinkinase (AMPK).
      Pharmacological substances, which stimulate AMPK-activity ameliorate insulin
      resistance induced by free fatty acids. Various therapeutical interventions for
      the improvement of insulin sensitivity, including weight loss, physical exercise,
      as well as metformin and glitazones, increase AMPK activity.

PMID- 15732246
TI  - [Diet and prevention of obesity].
AB  - Today obesity has already reached epidemic proportions in the industrialised
      nations and is seen as the main problem of this century. Because of the
      epidemiological situation and the risk of associated and resultant illnesses it
      is, in future, particularly important to strengthen the awareness of the problem
      amongst the general population, among experts in the fields of health and
      politics, as well as to develop public health strategies for health promotion, to
      reinforce target group oriented prevention measures in appropriate settings, and
      offer professional therapies in accordance with evidence-based guidelines. Within
      the framework of nutritional therapy, the general nutritional recommendations,
      (<30 En% fat, >55 En% carbohydrates, 10-15 En% protein) combined with a daily
      energy deficit of 300-1000 kcal are accepted for chronic disease prevention. In
      order to avoid long-term deficits in intake of macro- and micro-nutrients, a
      varied diet is recommended. The aim, not only of therapy, but also of prevention
      is a long-term change in dietary practices, which can only be achieved in
      combination with exercise and implementation of suitable behavioural methods.

PMID- 15732247
TI  - [Indication for bariatric surgery].
AB  - Morbid obesity is defined as obesity with body mass index (BMI) > or = 40 kg/m2
      with secondary serious diseases. Conservative treatment generally fails to
      produce long-term weight loss in these patients, since several bariatric surgical
      techniques have been developed which are based on gastric restriction and/or
      gastric malabsorption resulting in permanent weight loss over years. Preoperative
      evaluation might detect suitable patients and reduce both non-surgical and
      surgical complications. Postoperative follow-up in a multidisciplinary program,
      including specialists in various fields of medicine, e.g. surgery, internal
      medicine, radiology, paediatrics and nutritional surveillance are mandatory in
      the treatment of patients after obesity surgery. Bariatric surgery results in a
      major weight loss, with amelioration of most obesity-associated conditions. The
      most serious side effect of some surgical procedere is malnutrition.

PMID- 15732248
TI  - [The metabolic syndrome: epidemiology and diagnosis].
AB  - There has been a tremendous increase in overweight and obesity in industrialized
      countries. Because of its comorbidities obesity is defined as a disease. The
      abdominal fat distribution is associated with insulin resistance and with a
      number of cardiovascular risk factors; all of them are included in the metabolic
      syndrome. The metabolic syndrome can easily be defined by clinical symptoms and
      laboratory results, which are defined in the National Cholesterol Education
      Program (NCEP) Adult Treatment Panel III (AP III). Abdominal obesity is
      characterised by a waist circumference of over 102 cm for men and over 88 cm for
      women, plasma triglycerides >150 mg/dL, a low HDL cholesterol level (<40 mg/dL
      for men, <50 mg/dL for women), a blood pressure of over 130/85 mm Hg and an
      abnormal fasting glucose value >110 mg/dL.

PMID- 15732249
TI  - [Novel anti-obesity drugs].
AB  - Obesity is a chronic disease with a worldwide increasing incidence. The mainstay
      of therapy consists in modification of behaviour related to obesity such as
      overeating and physical inactivity. When these life-style modifying attempts
      fail, the use of anti-obesity drugs is warranted. Public health efforts and
      current anti-obesity agents have not controlled the increasing epidemic of
      obesity, which has led to an extensive research on novel anti-obesity agents.
      This review presents an overview on potential future candidates.

PMID- 15732250
TI  - [Impact of oncologic therapeutic concepts 2004].
AB  - The change of therapeutic concepts in oncology in the last few years is
      demonstrated in many examples like: influence on cell surface receptors, signal
      transduction, inactivation of oncogenes, activation of tumor suppressor genes,
      induction of apoptosis and inhibition of degradation of intracellular peptides.
      Therapeutic targets have become more specific in the last years using the results
      of experimental laboratories for clinical application. Unfortunately, however,
      only very few oncologic ailments can be influenced substantially so far. This may
      be explained by the hypothesis that the mechanisms of tumor growth can fluctuate-
      adaptation of tumor cell growth to the Controlling molecular biologic pattern may
      thus be the concequence. Finally we have to admit that in spite of all our
      efforts our methodology is still not precise enough (well illustrated by the
      example of the effectivity of Gefitinib) to reach our therapeutic goal--constant
      inhibition of tumor growth.

PMID- 15732251
TI  - [Clinical utility of the cardiac markers BNP and NT-proBNP].
AB  - BNP and NT-proBNP are new markers with potential applications for the diagnosis
      and management of patients with cardiovascular diseases. In patients with acute
      dyspnea, these markers might strengthen the clinical suspicion of decompensated
      congestive heart failure. Vice versa, below-threshold marker concentrations allow
      to virtually exclude significant left ventricular dysfunction in symptomatic
      patients. Furthermore, BNP and NT-proBNP are predictors of morbidity and
      mortality in patients with heart failure, but also in acute coronary syndrome,
      myocardial infarction, pulmonary embolism and other cardiovascular diseases. The
      markers therefore appear suitable for additional risk stratification.
      Independently from the clinical application, however, it is important to note
      that extracardiac variables may affect marker concentrations and need to be
      considered when marker concentrations are interpreted. Due to their diagnostic
      and prognostic value, the cardiac markers BNP and NT-proBNP have a clear
      potential to further improve the care of patients with cardiovascular diseases.

PMID- 15732252
TI  - [Experimental validation of the Evidence-Based Occupational Health paradigm and
      of the PICO model in the decision making process applied by occupational health
      physicians].
AB  - BACKGROUND: Health care organizations are increasingly aware of the need to apply
      quality assurance principles to serve their mission and there is an increasing
      pressure on health professionals to ensure that the practice is based on evidence
      of appropriateness. Medical specialists of different disciplines, including
      occupational health, are presently required to shift from habitual practices to
      evidence-based practices, and have began to use an approach based on the paradigm
      of Evidence-Based Medicine and of Evidence-Based Occupational Health (EBOH).
      OBJECTIVE AND METHODS: The study was carried out to analyse how the paradigm of
      the EBOH could be implemented in the search, analysis and synthesis of the best
      available evidence to apply in the decision-making process in occupational health
      practice. Out of 464 medical examinations consecutively performed by 4
      occupational health physicians, 6 cases were selected on the basis of their
      complexity and the need for further investigation. Each case was submitted to
      each of the 4 physicians, who were asked to make a decision according to the EBOH
      paradigm: i.e., (i) identification of the problem according to the PICO model,
      (ii) solution of the problem according to his/her internal evidence or experience
      (iii) search for scientific external evidence, (iv) critical appraisal of such
      evidence, (v) application of the evidence in the decision-making process, (vi)
      comparison between internal evidence and external evidence. Outcome measurements,
      including satisfaction of the physicians, were collected. RESULTS: No differences
      were found between the decisions based on external evidence or on internal
      evidence in about 50% of the cases (13/24). In about 1/3 of the cases (7/24) no
      agreement was observed between the decisions taken on the basis of internal and
      external evidence. In some cases (5/24) no useful information was added for the
      purposes of decision-making. In about 50% of the cases the professionals were
      satisfied with the information found in databases, due to its usefulness both in
      increasing their knowledge and in improving their practice. CONCLUSIONS: Due to
      their involvement in a corporate system, the participants were aware of the need
      to practice according to quality assurance principles and to relinquish
      ineffective and obsolete practices. They agreed with the need to search for the
      best available evidence with the aim of guaranteeing efficacious interventions.
      In spite of a number of obstacles to the application of the EBOH paradigm to
      occupational health practice, the study demonstrated that such approach can be
      successfully applied in this field and that it can be proposed for the search of
      appropriate solutions to the problems usually encountered in professional
      practice.

PMID- 15732253
TI  - [Assessment of working conditions in health care workers].
AB  - OBJECTIVE: Validation and first use of a self-completed questionnaire to assess
      opinion on working conditions in health professionals. METHODS: The questionnaire
      consisted of 40 items. It was developed via review of the literature and two
      focus groups. A reliability test-retest study was performed on 45 health
      professionals with different roles. Factorial validity and internal consistency
      of each derived subscale were evaluated on a wide sample of 514 professionals. In
      addition, the opinion of the health care professionals was evaluated and possible
      relationships were tested between total and subscale scores and the following
      variables: age, sex, professional role and years in the job. RESULTS: Weighted
      kappa was higher than 0.60 for 95% of the items, higher than 0.70 for 43% and
      higher than 0.80 for 20%. Factor analysis revealed that six factors--work content
      and organisation, physical fatigue, relationships, mental stress, hours of work,
      and physical environment--explained 57% of total variance. Cronbach's alpha
      coefficient of the subscales ranged from 0.70 to 0.91. Low levels of satisfaction
      in dfferent job aspects were found among general hospital staff. They were
      particularly dissatisfied with personal growth and development, fairness in
      incentives, dissemination of information, environment, support of new ideas and
      skills, career opportunities. In particular, satisfaction differed among the
      various professional roles. DISCUSSION: The questionnaire was found reliable and
      had a coherent factor structure, with six factors or subscales that showed good
      internal consistency. This questionnaire may be useful to assess satisfaction
      with work in health care staff. The preliminary results of its use suggest that
      satisfaction with different aspects of work is low.

PMID- 15732254
TI  - [Serologic investigation on the prevalence of Leptospira spp infection in
      occupationally exposed subjects].
AB  - BACKGROUND: Leptospirosis is a worldwide zoonotic infection with a high in
      tropical regions. OBJECTIVE: The aim of the present survey was to verify the
      occurrence of diffusion of leptospirosis infections in Eastern Sicily, in some
      groups (6 veterinarians, 34 farmers and 28 abattoir workers), who were considered
      at high occupational risk. METHODS: Serologic investigation were performed using
      the immunological method (Martin Petit test); the Leptospira serovars considered
      were: ictero-haemorrhagiae (Bianchi 1); canicola (Alarik); pomona (Mezzano 1);
      grippo-typhosa (Moskva V); bratislava (Riccio 2); sejroe (Topino 1); hardjo
      (Hardjoprajitno); saxkoebing (Mus 24). RESULTS: Contagion was observed in 16
      subjects out of 68 (23.5%), and the anti-leptospira antibodies detected were
      canicola, hardjo, sejroe grippo-typhosa e ictero-haemorrhagiae. CONCLUSIONS: The
      authors stress the importance carrying out periodic health surveillance in
      subjects working in wet and contaminated environments or who are continuously in
      contact with animals receptive to infections. The present study also confirms the
      need to adopt preventive measures such as vaccines, and control programs for
      activities at high risk.

PMID- 15732255
TI  - [Occupational asthma due to cyanoacrylate: a case-report].
AB  - BACKGROUND: An increased use of acrylic compounds is observed in different
      industries, home repairs and hobbies. These compounds are known to cause skin
      sensitisation, irritation of mucous membranes and bronchial asthma. Methyl
      cyanoacrylate is moderately likely to be a sensitizer, while ethyl cyanoacrylate
      might be a weak sensitizer. OBJECTIVES: Clinical evaluation of a case of
      occupational asthma due to cyanoacrylate. METHODS: A female worker, aged 32
      years, used ethyl cyanoacrylate daily. After 2 months she experienced dry cough
      and shortness breath. Some weeks later she developed bronchial asthma. The
      diagnosis of occupational asthma was based on the work-related symptoms and the
      inhalation challenge test result. RESULTS: A late asthmatic response was observed
      with a maximum fall in FEV1 of 26% 345 minutes after exposure. Complete clinical
      and functional recovery was observed after inhalation of a broncho-dilating
      agent. CONCLUSIONS: Acrylates are new occupational sensitising agents, causing
      rhinitis and asthma. It is not possible to perform prick tests or specific IgE
      measurements for these compounds. The bronchial challenge test is therefore the
      sole valid test for the diagnosis of occupational asthma.

PMID- 15732256
TI  - [Survey on health status of workers exposed in the past to carcinogens in a glass
      factory in Leghorn, Italy].
AB  - BACKGROUND: For a few years now in Italy there has been wide discussion on the
      advisability of developing health surveillance programmes for workers who were
      exposed to occupational carcinogens in the past (incompliance with Italian D.Lgs.
      626/94, art. No. 69). The purpose of the present paper was to contribute to the
      discussion on operative guidelines for public or private Occupational Health
      Services intending to address this issue. METHODS: A cross-sectional survey was
      undertaken on former workers of a glass factory located in Leghorn, Italy. Six
      hundred and seventy-seven workers discharged in the period 1/1/1942 - 30/6/1992,
      with at least 1 year of service, resident in the area of Leghorn, were identified
      from the personnel records of the company and invited to medical examination at
      the local public Occupational Health Service. A structured questionnaire was
      developed in order to standardize the collection of occupational and health
      histories. RESULTS: 370 subjects were examined and for each of them occupational
      and health histories were collected. Occupational exposure to carcinogens in the
      factory in the last decades was reconstructed using the workers' occupational
      histories and the available plant records: 3 periods with different production
      activities (1942/49, 1950/69, 1970/92), and 4 main carcinogens (asbestos, PAH,
      silica and glass fibres) were identified. Thirty cancers were recorded and 10 of
      these were occupationally related. CONCLUSIONS: The health survey allowed
      occupational exposures to carcinogens to be defined in a factory where historical
      environmental data were not available. It was also possible to assess individual
      past occupational risk and provide information to each former worker on his risk,
      on available preventive measures, and on possible diagnostic, therapeutic and
      insurance procedures available in relation to diseases related to the different
      hazards. Via this survey it was also possible to identify and notify the Italian
      Institute of Insurance against Occupational Diseases and Accidents of 6 cases of
      bladder cancer, i.e., cancers with long survival that would be impossible to
      identify via current health data bases.

PMID- 15732257
TI  - [Occupational exposure to 50 Hz magnetic fields in workers employed in various
      jobs].
AB  - BACKGROUND: Information on occupational exposure to ELF magnetic fields (MF) in
      workers is largely insufficient, and is mostly based on results obtained in
      Scandinavian countries and North America. Accordingly, the collection of further
      data is needed, especially in workers exposed in other countries, including in
      Italy. METHODS: One hundred and fifty workers (84 males and 66 females) employed
      in 28 different jobs in the Emilia-Romagna Region of Italy were examined.
      Individual exposure was measured using personal monitors worn on the hip in a
      belted pouch during three whole work-shifts (8 hours each) of a normal working
      week. A sampling interval of 10 seconds was adopted, resulting in the collection
      of more than 8600 measurements for each worker. The individual Time-Weighted
      Average (TWA) occupational exposure of workers was calculated as the arithmetic
      mean of all measurements during each work-shift. Environmental non-occupational
      exposure was also measured. RESULTS: The 50 degrees percentile of individual TWA
      in the whole group was 0.15 microT, and the 5 degrees - 95 degrees percentile was
      respectively 0.02-1.45 microT. Job-related exposure (expressed as the mean of the
      TWA measured in all workers engaged in that job) was highest in substation
      electric power plant workers (1.12 microT) and in sewing machine workers (0.84
      microT), but was lower than 0.2 microT in more than the 70% of the examined jobs.
      Considering the geometric mean of individual TWA are 27 out of 28 the jobs
      inducing an exposure lower than 0.2 microT. The lowest exposure was observed in
      infant school teachers. A high variability was observed among different workers
      engaged in the same occupation, mainly in substation electric power plant
      workers, machine testers and grinders in the engineering industry and in sewing
      machine workers and quality control in garment production. A marked variability
      of the pattern of exposure during the work-shift was also observed The overall
      environmental (non-occupational) exposure was 0.044 microT, and individual
      exposure was lower than 0.2 microT in about 97% of the examined subjects.
      Occupational exposure was usually higher and was not correlated with
      environmental exposure. CONCLUSIONS: The results show that the occupational
      component of overall exposure must be considered in studies on the biological
      effects of ELF-MF in populations. The high variability observed among workers
      engaged in the same occupation and the variability of the pattern of exposure
      certainly constitute major problems and could be a cause of the scarce coherence
      of the results of epidemiological studies on biological effects of ELF-MF to
      date. An improvement in protocols for the evaluation of exposure in workers,
      including the use of personal monitoring, is certainly needed.

PMID- 15732259
TI  - The case for rhinoviruses in the pathogenesis of multiple sclerosis.

PMID- 15732258
TI  - [Comment on the guidelines for the health surveillance of individuals exposed to
      carcinogens at work].

PMID- 15732260
TI  - Multiple sclerosis diagnostic criteria: three years later.
AB  - New diagnostic criteria for multiple sclerosis (MS) were developed by an
      International Panel in 2001 and have had wide distribution and discussion since
      publication. These provided the first formal incorporation of magnetic resonance
      imaging (MRI) in a diagnosis work-up for patients suspected of having MS. The so
      called McDonald criteria have been studied in retrospective and prospective
      analyses for sensitivity, specificity and utility, and have been proven to
      compare favourably or to be an improvement upon prior MS diagnostic criteria. The
      purpose of the current review is to present and evaluate the key studies that
      have been performed using the McDonald criteria since 2001 and to set the stage
      for an upcoming re-evaluation of the new criteria based on data-driven
      information gathered since their development.

PMID- 15732261
TI  - Serum levels of insulin-like growth factor-1 and insulin-like growth factor
      binding protein-3 in relapsing and primary progressive multiple sclerosis.
AB  - Using radioimmunoassay we measured serum levels of insulin-like growth factor
      (IGF)-1 and IGF binding protein (IGFBP)-3 in patients with relapsing multiple
      sclerosis (MS) and a benign course (Expanded Disability Status Scale (EDSS) < or
      =3 despite > 10 years disease duration), relapsing MS with cumulative disability
      leading to an EDSS score >4 within 10 years of disease duration, primary
      progressive MS and healthy controls. We found no differences in IGF-1 and IGFBP-3
      serum levels, and the IGF-1/IGFBP-3 ratio between the four groups. However, there
      was a significant correlation (P =0.005) between IGFBP-3 serum levels and both
      the progression index of disability and the Multiple Sclerosis Severity Score in
      patients with primary progressive MS.

PMID- 15732262
TI  - Immunological heterogeneity of multiple sclerosis in Sardinia and Sweden.
AB  - Subjects from Sardinia, Italy, are relatively homogeneous compared to Swedes.
      Although ethnically distant, both populations have similarly high multiple
      sclerosis (MS) incidence rates. Pro- and anti-inflammatory cytokines and their
      receptors, signalling molecules and other immune response-associated factors
      might influence MS pathogenesis, though definite proof is missing. The study of
      populations with similar MS incidence but different genetic and environmental
      background could make possible the definition of factors that relate to such
      background differences. We selected untreated female MS patients from Sassari,
      Sardinia, and Stockholm, Sweden, and corresponding sex- and age-matched healthy
      controls (HC), to study blood mononuclear cells (MNC) for mRNA expression of 20
      immune response-related genes considered relevant in MS, employing real-time PCR.
      Higher expression of IL-12p40 mRNA was confined to MS from both Sassari and
      Stockholm, compared to corresponding HC. MS patients from Sassari, but not
      Stockholm, expressed higher TNF-alpha compared to corresponding HC. MS patients
      from Stockholm, but not Sassari, expressed higher IL-6. Indoleamine 2,3
      dioxygenase (IDO), a molecule necessary in tolerance induction, was lower in MS
      from Stockholm compared to corresponding HC. This was not observed in Sassari. No
      differences were detected for other members of the IL-12 family, other Th1 and
      Th2 cytokines, and the signalling molecules Stat 4 and 6. The results corroborate
      a pro-inflammatory state in MS as reflected by high expression of IL-12, TNF
      alpha and IL-6, although the extent of expression of TNF-alpha, IL-6 and IDO
      differs between strictly matched MS patients from different high-incidence areas.
      This might result from genetic and/or environmental differences. They may account
      for some of the discrepancies regarding immune response-related molecules
      previously reported in MS. In conclusion, a pro-inflammatory state exists in MS
      patients from Sassari as well as Stockholm. The changes of pro-inflammatory and
      other immune response-related variables differ however between the two MS
      populations. This may be attributed to the genetic and/or environmental
      background.

PMID- 15732263
TI  - Multiple sclerosis and nutrition.
AB  - Benefits from any particular diet in multiple sclerosis (MS) have not yet been
      proven. It is, however, frequent that malnutrition may potentially exacerbate the
      symptoms of MS. There is some evidence that a high intake of saturated fat
      increases the incidence of MS. Epidemiological studies imply that unsaturated
      fatty acids may have a positive effect on the course of MS. However, the results
      of controlled studies are ambiguous. A meta-analysis of three small controlled
      clinical trials suggests a benefit from linoleic acid. Intake of Vitamin D is
      associated with a lower incidence of MS. In MS, the risk of osteoporosis is high,
      and prophylactic vitamin D and calcium should be considered at an early stage.
      The role of minerals, trace elements, antioxidants, vitamins or fish oil is
      unclear. The possible relationships between diet and MS have not been subjected
      to adequate study. It seems possible that in the future, diets or dietary
      supplements may become recommended forms of treatment for MS.

PMID- 15732264
TI  - Treatment patterns of multiple sclerosis patients: a comparison of veterans and
      non-veterans using the NARCOMS registry.
AB  - Multiple sclerosis (MS) is a chronic illness of the central nervous system, with
      a highly variable clinical course. Available therapies are only partially
      effective and as a consequence treatment patterns between patients can be varied.
      Longitudinal databases consisting of large cohorts where successive and
      sequential data is collected may reveal disease and treatment characteristics not
      apparent when data is gathered during clinical trials that consist usually of
      relatively homogeneous patients followed for short durations. We analysed data
      from the North American Research Committee on Multiple Sclerosis registry, a self
      reported database, to assess MS patient characteristics and treatment patterns,
      with a focus on veterans. We show that the Veteran Healthcare Administration
      (VHA) system of medical centres care for a greater number of patients with higher
      average disability but not necessarily patients who report primary progressive or
      actively worsening disease. We also show that the VHA medical centres appear to
      better provide multidisciplinary care, particularly in the areas of social work,
      physical therapy and urology. In general, treatment patterns for symptomatic
      therapies follow similar patterns across veterans and non-veterans groups.
      Treatment patterns for immunomodulatory agents suggest that VHA veterans use IMA
      less frequently than either non-VHA veterans or non-veterans.

PMID- 15732265
TI  - Randomized study of once-weekly interferon beta-1la therapy in relapsing multiple
      sclerosis: three-year data from the OWIMS study.
AB  - BACKGROUND: Once weekly interferon beta-1a for multiple sclerosis (OWIMS)
      demonstrated modest, but significant, magnetic resonance imaging (MRI) benefit of
      once-weekly (qw) interferon (IFN) beta-1a at 48 weeks, but no significant effect
      on relapses. OBJECTIVE: An OWIMS extension permitted assessment of longer-term
      efficacy/safety of qw IFN beta-1a in relapsing-remitting multiple sclerosis
      (RRMS). METHODS: Placebo patients were rerandomized to IFN beta-1a, 22 or 44 mcg
      qw, for two additional 48-week intervals. Primary outcome was MRI lesion
      activity. Relapse rate and other MRI measures were secondary outcomes. RESULTS:
      After three years, median (mean) T2 lesion count/patient/scan was 1.3 (2.6) for
      44 mcg, 1.7 (3.3) for 22 mcg, 1.7 (3.4) for placebo/22 mcg, 2.0 (3.6) for
      placebo/44 mcg (all differences not significant). Annualized relapse rates were
      lowest for 44 mcg (0.77) versus other groups (0.83-0.86, not significant).
      Persistent neutralizing antibodies did not affect relapse rates, but MRI active
      lesions were increased in antibody-positive patients receiving 44 mcg compared to
      antibody negative patients. CONCLUSIONS: In RRMS, once weekly IFN beta-1a,
      particularly 44 mcg, can induce a significant MRI, but not relapse, effect,
      compared with placebo. No significant dose effect was seen. In contrast to the
      significant effect observed with three-times-weekly dosing of subcutaneous IFN
      beta-1a compared with placebo, this study confirms the lack of meaningful
      clinical benefit with once-weekly dosing.

PMID- 15732266
TI  - Stopping beta-interferon therapy in multiple sclerosis: an analysis of stopping
      patterns.
AB  - Estimates of the beta-interferon (IFNB) stopping rate in relapsing-remitting
      multiple sclerosis (RRMS) and secondary progressive MS (SPMS) vary and have been
      mainly derived from multicentre studies. This is a retrospective, hospital chart
      based study of 394 patients treated by a single neurologist for up to eight
      years. The aims of the study were to ascertain the frequency and timing of IFNB
      discontinuation in a well supported cohort, and to investigate whether the
      clinical disease type at the initiation of IFNB or the reason for discontinuation
      influenced stopping rates. The median follow-up was 49 months. The overall IFNB
      stopping rate was 28% over five years; there was a significant difference between
      the IFNB stopping rates for RRMS (14%) and SPMS (23%) after three years of follow
      up (P =0.0003). Patients stopped IFNB due to side effects after a median of 13
      months, and due to failure of therapy after a median of 35 months (P =0.0004).
      Significantly more patients with SPMS than with RRMS stopped IFNB due to
      treatment failure (P =0.037). CONCLUSION: IFNB discontinuation occurred earlier
      in the treatment course when due to side effects. Stopping IFNB therapy was more
      common in SPMS and was more often due to treatment failure than side effects.

PMID- 15732267
TI  - Altered cytokine responses to cognitive stress in multiple sclerosis patients
      with fatigue.
AB  - This study intended to examine if the immune response to a cognitive task as a
      variant of psychological stress in MS patients is distinct from healthy controls.
      The experiment was part of a larger study on mechanisms and measurements of MS
      fatigue. Patients (n =23) and controls (n =25) participated in a cognitive task
      lasting 40 minutes, in which the heart rate was continuously monitored. Blood
      samples were taken at baseline and directly after the stress-inducing task Whole
      blood stimulated cytokine production representative of the TH-1 (i.e. IFNgamma,
      TNFalpha) and TH-2 paradigm (i.e. IL-10) was evaluated in relation to disability,
      fatigue, cognitive deficit, and anxiety. Patients scored high on a disease
      specific fatigue score compared to controls, whereas baseline cytokine patterns
      did not differ between the groups. MS patients displayed a blunted response of
      IFNgamma (P =0.03) whereas TNFalpha and IL-10 responses did not change.
      Additionally MS patients showed a significantly lower heart rate increase after
      the task (P <0.001). Cognitive impairment was associated with a decreased heart
      rate reactivity (P =0.02) while depressive symptoms correlated with stronger IL
      10 responses (P =0.05). Overall, cognitive stress induces IFNgamma production in
      healthy controls but not in MS patients with fatigue. Furthermore, a reduced
      cardiac response might indicate an autonomic dysfunction in this group of
      patients.

PMID- 15732268
TI  - Treating learning impairments improves memory performance in multiple sclerosis:
      a randomized clinical trial.
AB  - This randomized clinical trial utilized established techniques to improve new
      learning and memory performance in multiple sclerosis (MS) participants with
      learning impairment. Participants were 29 individuals with clinically definite MS
      with documented learning deficits, randomly assigned to the experimental or
      control group. The experimental group underwent eight sessions of the Story
      Memory Technique (SMT), while the control group participated in eight sessions of
      memory exercises. Neuropsychological assessment was conducted at baseline,
      immediately following treatment and 5 weeks later to assess outcome. When
      stratifying participants by degree of learning deficits, a significant treatment
      effect was noted. MS participants with moderate-severe impairment in learning
      showed a significant improvement in learning abilities when compared to controls,
      (t(19) =3.32, P<0.01) evident in 88% of participants in the experimental group.
      Little improvement was noted in MS participants with mild learning impairments.
      Significant self-reported improvements in memory were noted in MS participants
      that underwent treatment, but not those that did not undergo treatment (t(26)
      =2.55, P<0.01). Results indicate that learning and memory deficits in MS can be
      effectively treated through a memory rehabilitation program utilizing context and
      imagery to improve new learning. Appropriate patient selection is important, with
      moderately-severely impaired individuals showing significantly greater benefit
      from treatment.

PMID- 15732269
TI  - Subjective cognitive complaints relate to mild impairment of cognition in
      multiple sclerosis.
AB  - Cognitive impairment is common in multiple sclerosis (MS), but cannot be reliably
      predicted by physical impairment. The negative impact of cognitive impairment
      makes early detection important, but subjective cognitive complaints may be
      attributed to depression. We examined the relationship between subjectively
      reported and objectively measured cognitive impairment in MS, adjusting for mood.
      A neuropsychological battery, the Multiple Sclerosis Functional Composite (MSFC),
      the Mental Health Inventory (MHI), the Modified Fatigue Impact Scale (MFIS), the
      Perceived Deficits Questionnaire (PDQ) were administered to 136 patients.
      Demographically-adjusted cognitive scores were calculated. Subjective impairment
      was defined as PDQ score >2 standard deviations above that for healthy persons.
      We modeled the relationship of cognitive scores (independent variables) to being
      subjectively impaired (dependent variable) using logistic regression. Immediate
      Memory (IM) and Processing Speed Index (PSI) scores were non-linearly related to
      subjective impairment Patients were less likely to report subjective impairment
      if their PSI was normal (OR =0.11; 0.02-0.73) or markedly impaired (OR =0.17;
      0.03-0.91), compared to mildly reduced PSI. In young patients decreases in IM
      were associated with increased subjective impairment (OR = 1.25; 1.07-1.47).
      Subjectively reported impairment reflects subtle declines in PSI and IM
      independent of mood, fatigue, and physical impairment Cognitive complaints should
      not be discounted due to depression.

PMID- 15732270
TI  - Evaluation of the Modified Fatigue Impact Scale in four different European
      countries.
AB  - OBJECTIVE: To evaluate the psychometric properties of the Modified Fatigue Impact
      Scale (MFIS) in four different European countries. METHODS: Individuals with
      definite multiple sclerosis (MS) were selected from centres in Italy (n =50),
      Spain (n =30), Slovenia (n =50) and Belgium (n =51) and completed the MFIS and
      the Fatigue Severity Scale (FSS) twice (interval < or =3 days). RESULTS: In all
      four samples, the MFIS demonstrated a good reproducibility (intraclass
      correlation coefficient > or = 0.84), with no significant differences between
      countries (P =0.77). Moderate correlations were found between the MFIS and FSS.
      No significant correlations were found between the MFIS and age, gender, type of
      MS, duration of the disease or EDSS score. Factor analysis of all samples (n =
      181) could not completely confirm the original assumptions concerning the
      physical, cognitive and psychosocial component The total score, the physical and
      the cognitive subscale of the scale were homogeneous (Cronbach's alpha 0.92, 0.88
      and 0.92, respectively), but the psychosocial subscale had a Cronbach's alpha of
      0.65. CONCLUSIONS: No cultural or linguistic differences were found in the
      psychometric properties of the Belgian, Italian, Slovenian or Spanish version of
      the MFIS. We recommend this scale for research purposes and in clinical practice.
      Due to the limited value of the psychosocial subscale, we recommend interpreting
      this subscale with caution.

PMID- 15732271
TI  - Responsiveness of the Multiple Sclerosis Impairment Scale in comparison with the
      Expanded Disability Status Scale.
AB  - The Multiple Sclerosis Impairment Scale (MSIS) is a measure of accumulated
      deficits assessed by means of a standard neurological examination. We compared
      the responsiveness of the MSIS with that of the Expanded Disability Status Scale
      (EDSS). We reviewed 4300 records collected systematically from 1995 to 2003 and
      identified 534 patients who had clinically definite multiple sclerosis and had
      had at least two clinical assessments with a time interval of 2-5 years. The rate
      of deterioration was significantly higher on the MSIS than on the EDSS. The
      annualized change in EDSS exhibited a maximum at baseline EDSS 4 and a subsequent
      rapid decline at higher baseline EDSS, while the annualized change in MSIS was
      fairly stable over a wide middle range of baseline MSIS. The variance of the
      annualized change in EDSS fluctuated markedly between the baseline EDSS
      categories, being highest at baseline EDSS 2, while the variance of the
      annualized change in MSIS was stable. The study indicates that the responsiveness
      of the MSIS is better than that of the EDSS in terms of both magnitude and
      stability over the range of measurement

PMID- 15732272
TI  - The Paced Auditory Serial Addition Test: to what extent is it performed as
      instructed, and is it associated with disease course?
AB  - One commonly used outcome measure in multiple sclerosis (MS) clinical trials is
      the Multiple Sclerosis Functional Composite, which includes the Paced Auditory
      Serial Addition Test (PASAT) as a measure of cognitive function. Concerns have
      been raised about the standard PASAT scoring method, whereby the number of
      correct responses is summed. This method does not take into account whether the
      test is performed as intended, which may affect interpretation of the results.
      Accordingly, another scoring method has been proposed, which examines the number
      of times a correct response is immediately preceded by another correct response
      (termed a dyad). We compared the two scoring methods for the PASAT, and found
      that the mean percentage of correct responses not accounted for by dyads ranged
      from 27.5% to 49.5%, indicating that much of the time the test is not performed
      as instructed. We also examined disease course and the PASAT score, as studies
      have produced conflicting results as to whether disease course is associated with
      cognitive impairment. Although disease course was significantly associated with
      the PASAT score, it accounted for little of the variation in scores, even when
      adjusting for other predictors. Finally, as 14.2% of participants refused to do
      the PASAT or failed to complete it, we also examined whether the Perceived
      Deficits Questionnaire (PDQ), a self-reported measure of cognitive function, is a
      potential proxy measure for the PASAT. The correlation between the two tools was
      low (-0.14), suggesting that the PDQ is not a useful substitute for the PASAT.

PMID- 15732273
TI  - Brachial neuropathy after immunosuppression and stem cell transplantation for
      multiple sclerosis.
AB  - We present a case of brachial neuritis in an adult male who underwent high-dose
      immunosuppressive therapy and autologous stem cell transplantation (SCT) for
      primary progressive multiple sclerosis (MS). Brachial neuropathy following SCT
      has not previously been reported in patients with MS. The etiology of peripheral
      nerve dysfunction following SCT remains obscure.

PMID- 15732274
TI  - Griseofulvin: a novel addition to anti-multiple sclerosis ammunition?

PMID- 15732275
TI  - Relevance of clinical findings for multiple sclerosis diagnosis in the MRI era: a
      case report.

PMID- 15732276
TI  - Ethical issues in MS clinical trials.

PMID- 15732277
TI  - Update on the international project on pathologic correlates in MS.

PMID- 15732278
TI  - Immunologic correlates of MS pathologic subtypes.

PMID- 15732279
TI  - Mri correlates of MS pathologic subtypes.

PMID- 15732280
TI  - Pathologic classification systems in MS: what is their significance?

PMID- 15732281
TI  - Genetics of lupus nephritis.
AB  - Susceptibility to lupus nephritis is the end-result of complex interactions
      between polymorphic genetic factors involved in the regulation of immune
      responses. In humans, genome-wide screens and candidate-gene analyses led to the
      identification of several loci containing potential targets (FcgammaRIIa, PTPN22,
      PD-1, IL-10) for physiopathological research and therapeutic interventions. In
      mice, the generation of congenic mice, bearing in a normal genetic background one
      single disease-associated locus, greatly improved our understanding of the
      mechanisms mediating the genetic contribution to the disease. In the future, the
      identification of disease-associated genes will open new perspectives for the
      development of more targeted therapies of lupus nephritis.

PMID- 15732282
TI  - Cytokine expression in lupus kidneys.
AB  - Although far from complete, the picture of cytokines present in systemic lupus
      erythematosus (SLE) glomerulonephritis is already complex. Proinflammatory
      cytokines, such as TNF, IL-6, IL-1, and IL-18 are upregulated, as are both Th1
      and Th2 cytokines, with different implications. In many instances, the local
      effects may be different from the systemic immunoregulatory ones. For some
      proinflammatory cytokines, and TNF in particular, the local proinflammatory ones
      may be more relevant to the disease. This may help solve discrepancies between
      different murine models of the disease and provide a better rationale for
      targeting certain cytokines in human SLE.

PMID- 15732283
TI  - Pathogenic autoantibodies in lupus nephritis.
AB  - Lupus nephritis is a major complication of systemic lupus erythematosus (SLE) and
      is associated with a high rate of morbidity and mortality. While many different
      immunologic and nonimmunologic factors contribute to disease expression in lupus
      nephritis, a large body of evidence suggests that the production of anti-DNA
      antibodies and the formation of glomerular immune deposits are important initial
      events in the pathogenesis of the disease. This review will summarize our current
      understanding of the differences between pathogenic and nonpathogenic
      autoantibodies, the mechanisms by which these autoantibodies induce renal injury
      and the effector mechanisms which are subsequently activated by the deposited
      autoantibodies that ultimately lead to the expression of the different lupus
      lesions.

PMID- 15732284
TI  - Clinical presentation and monitoring of lupus nephritis.
AB  - The diversity of clinical presentations of lupus nephritis parallel the diversity
      of pathologic lesions seen in the kidneys of patients with SLE. Renal
      manifestations range from asymptomatic hematuria or proteinuria to overt
      nephritic and nephrotic syndromes, rapidly progressive glomerulonephritis, and
      chronic renal failure. Subclinical nephropathy both during presentation and
      during monitoring of disease activity is frequently missed because of the
      notorious unreliability of routine screening urinalyses performed in high
      throughput clinical pathology laboratories. Requisitions for urine microscopy
      should be flagged for special attention in patients at risk for lupus nephritis.
      Depression of classic complement pathway components and high titers of anti-DNA,
      anti-nucleosome, or anti-Clq antibodies identify patients are increased risk of
      renal involvement or flares of nephritis. Several disease activity and damage
      indexes are available, but they are mostly used in clinical research setting and
      none has achieved wide use for standard clinical practice.

PMID- 15732285
TI  - Pathology of lupus nephritis.
AB  - The glomerular pathology of lupus nephritis is the result of diverse immune
      insults which are probably of independent pathogenetic origins. Although lupus
      nephritis is looked upon as a classic example of immune complex-induced
      microvascular injury resulting from circulating DNA double stranded
      polynucleotide antigens/anti-DNA antibody complexes, other mechanisms, including
      in situ reactivity of free antibody with fixed antigens and the role of
      sensitized T-cells, are probably an important part of the picture. This
      complexity makes categorization of glomerular pathology into a clinically
      relevant classification an important goal so that our experiences can be reliably
      compared. This review describes the various glomerular lesions commonly
      encountered in lupus nephritis and, based upon data derived from experimental
      models, emphasizes the importance of understanding the clinical relevance of the
      reported morphology. We point out that the severity of glomerular damage is not
      merely the accrued result of immune complex induced injury to individual
      capillaries, but involves capillary necrosis and thrombosis, neither of which may
      have anything to do with immune complexes or immune aggregates. In fact, the
      segmental lesions of glomerular capillary necrosis and thrombosis may have a
      great deal to do with the response to therapy and the ultimate outcome of the
      patient. While discrete morphologic lesions such as mesangiopathy, acute
      inflammation, necrosis, thrombosis, epimembranous lesions and podocytopathy are
      readily described, it is important to note that any given case can represent any
      combination of these insults. In this context, the new proposed International
      Society of Nephrology Classification is presented and its strengths and
      weaknesses discussed.

PMID- 15732286
TI  - Prognostic factors in lupus nephritis.
AB  - Systemic lupus erythematosus (SLE) is a heterogeneous disorder and its renal
      manifestations are protean. The course and prognosis of lupus nephritis is
      dependent on a large number of demographic, histopathological, serological,
      racial, socioeconomic and time dependent factors. Moreover, the initial and
      maintenance therapeutic regimens may also influence the long term renal outcome.
      This article reviews the important prognostic factors that have been reported in
      literature. The management strategy of lupus nephritis should be individualized
      and based on a composite of these parameters.

PMID- 15732287
TI  - Renal manifestations of the antiphospholipid syndrome.
AB  - Renal thrombotic manifestations have been reported since the earliest
      descriptions of the antiphospholipid (Hughes) syndrome (APS). The spectrum of
      clinical features associated with antiphospholipid nephropathy continues to
      widen. This review will highlight recent developments such as the prevalence of
      hypertension, livedo reticularis and renal artery stenosis as well as the
      ultrastructural changes seen in antiphospholipid nephropathy. The increasing
      risks of renal transplantation in antiphospholipid antibody positive patients is
      also discussed leading some authors to question whether these patients should
      undergo transplantation at all.

PMID- 15732288
TI  - Lupus nephritis flares.
AB  - The clinical course of lupus nephritis varies remarkably among SLE patients, even
      between those with the same histological type. Current immunosuppressive agents
      induce remission in the majority of the patients with proliferative lupus
      nephritis, but a substantial proportion of them - ranging in different studies
      from 27% to 66% - will flare. Flares represent a significant problem because of
      the potential for cumulative damage that may lead to deterioration of renal
      function as well as toxicity due to the additional immunosuppression. Maintenance
      therapy with azathioprine, mycophenolate mofetil or quarterly pulses of
      cyclophosphamide is usually recommended. Renal flares can be characterized as
      nephritic or nephrotic and can be mild or severe. The majority of the patients
      that flare restore renal function, if diagnosed early and treated promptly.
      However, current immunosuppressive agents have limitations concerning efficacy
      and toxicity profiles. Unresolved management issues include the value of repeat
      renal biopsy and issues related to optimal strategy/regimen to prevent flares.
      Renal flares are an important feature of the natural history of lupus nephritis
      and provide an opportunity for additional preventive strategies, as well as
      measures of efficacy in future therapeutic trials.

PMID- 15732289
TI  - Cyclophosphamide in lupus nephritis.
AB  - Although not licensed for systemic lupus erythematosus (SLE), cyclophosphamide
      (CYC) has become over the last two decades the most widely prescribed cytotoxic
      drug for lupus nephritis (LN). A PubMed search using 'lupus nephritis and
      cyclophosphamide' as key words identifies not less than 454 papers on the topic.
      This should, however, not disguise the fact that its use is still controversial
      and that many issues remain debated, such as the timing and length of treatment,
      the route of administration and the ideal dosage. In this review, the different
      CYC regimes on the basis of the results of prospective randomized trials
      performed in LN patients is discussed.

PMID- 15732290
TI  - Mycophenolate mofetil in lupus nephritis.
AB  - There is an increasing body of literature suggesting the efficacy and
      tolerability of mycophenolate mofetil (MMF) for the treatment of lupus nephritis.
      The rationale for its use is based upon its successful profile as an
      immunosuppressive agent for prevention of allograft rejection, as well as studies
      in murine models of lupus which have reported improved renal function and animal
      survival compared to placebo. This report reviews the data regarding MMF therapy
      in murine lupus models, and describes the initial anecdotal experience with MMF
      in human lupus, especially in patients with glomerulonephritis who were
      unresponsive to corticosteroids and cyclophosphamide, or who had unacceptable
      toxicity on this standard of care regimen. The results of several nonblinded,
      controlled clinical trials are also described, in which MMF was compared to
      intravenous or oral cyclophosphamide in patients with lupus nephritis. MMF was
      found to be well tolerated, with most studies showing fewer infections than that
      associated with cyclophosphamide. Efficacy of MMF was at least equivalent to
      cyclophosphamide, and therefore appears to provide an alternative as a standard
      of care for induction and maintenance treatment of lupus nephritis.

PMID- 15732291
TI  - Membranous lupus nephritis.
AB  - Membranous lupus nephritis (MLN) represents about 20% of clinically significant
      renal disease in lupus. Few studies have addressed directly the pathogenesis of
      MLN. Our assumptions about the underlying mechanisms are based on the combination
      of extrapolations from idiopathic membranous nephritis (mainly from animal
      models) and proliferative lupus nephritis. Natural history studies of MLN suggest
      a relatively low rate of progression to end-stage renal disease but a high rate
      of significant comorbidities. Historical changes in the criteria for pathologic
      diagnosis and classification of membranous lupus nephropathy have precluded
      definitive descriptions of the natural history, prognosis and treatment of this
      disorder. Patients with membranous lupus nephropathy should be treated early with
      angiotensin antagonists to minimize proteinuria, as well as lifestyle changes and
      appropriate drugs to reduce attendant cardiovascular risk factors. In patients
      with protracted nephrotic syndrome, consideration should be given to
      immunosuppressive therapies, including corticosteroids, cyclosporine,
      mycophenolate and cyclophosphamide. Prospective controlled trials are clearly
      needed in order to establish solid clinical practice guidelines for use of these
      drugs and other experimental therapies currently under study in membranous lupus
      nephropathy.

PMID- 15732292
TI  - Optimal care of lupus nephritis patients.
AB  - Optimal care of lupus nephritis patients should include the treatment of
      proteinuria and hypertension, other measures to delay the progression of chronic
      kidney disease, the vigorous management of cardiovascular risk factors and
      finally, the treatment of advanced chronic kidney disease and its consequences.
      These topics are briefly reviewed in the present paper, with particular emphasis
      on the recent progresses in antiproteinuric treatment.

PMID- 15732293
TI  - Novel therapies in lupus nephritis.
AB  - Renal disease continues to cause major morbidity and some mortality for around 30
      40% of patients with systemic lupus erythematosus (SLE). Although the
      combinations of prednisolone and azathioprine or prednisolone and
      cyclophosphamide have been beneficial to many patients with SLE, they are not
      always effective and have significant side effects. It is very encouraging that
      new immunosuppressive drugs such as mycophenolate mofetil and more targeted
      therapies e.g., anti-CD20 are coming rapidly to larger scale clinical trials. The
      treatment of lupus nephritis is set to change quite rapidly in the next decade.
      In this review we highlight the likely major therapeutic advances.

PMID- 15732294
TI  - Lupus nephritis in children.
AB  - In systemic lupus erythematosus renal involvement is more frequent in children
      than in adults. Overall, 60-80% of children with systemic lupus erythematosus
      have urinary or renal function abnormalities early in the disease course. In 90%
      of patients, renal disease occurs within two years from disease onset. Clinically
      significant renal involvement ranges from asymptomatic urinary findings to
      nephrotic syndrome and renal failure. Long-term prognosis is similar to that
      observed in adults. Treatment aspects that are peculiar to children include drug
      side-effects, such as growth inhibition induced by steroids, the need to consider
      morbidity-related issues with respect to the very long life expectancy of
      patients and the problems related to the impact of disease in adolescents. The
      recent availability of a childhood SLE definition of improvement and the presence
      of large international paediatric rheumatology networks should, in the future,
      facilitate the implementation of controlled clinical trials devoted to paediatric
      SLE.

PMID- 15732295
TI  - Pregnancy after lupus nephritis.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that affects
      primarily women, commonly in their reproductive years but does not influence
      fertility. For these reasons, the clinician has often to face the many problems
      of pregnancy in patients with SLE including the influence of SLE on fetal outcome
      and that of pregnancy on SLE. As there is increasing evidence of an important
      role of sex hormones in immunity, the influence of pregnancy on SLE is probably
      due to the changes in sex hormone levels during pregnancy that are more important
      than in any other period of life. Early reports emphasized a high fetal and
      maternal risk in particular in patients with lupus nephritis. However in the same
      period the prognosis of lupus nephritis was poor, so it was difficult to know
      whether pregnancy actually influenced the prognosis of the disease. More recent
      prospective studies indicate that pregnancy is safe for the majority of mothers
      if it is planned when SLE is quiescent. Instead, although fetal risk has been
      progressively reduced in the last 40 years, it continues to be higher than that
      occurring in pregnancies of healthy women. In particular the presence of
      antiphospholipid antibodies considerably worsen the fetal outcome.

PMID- 15732296
TI  - Renal transplantation in lupus nephritis.
AB  - Most patients with systemic lupus erythematosus (SLE) are suitable candidates for
      renal transplantation. However, a number of them may present some disease-related
      problems. As cardiovascular disease is a leading cause of morbidity and mortality
      in SLE patients, a careful pretransplant cardiovascular screening is recommended.
      A search for antiphospholipid antibodies is also useful as the presence of these
      antibodies can cause an early graft thrombosis. The risk of recurrence of SLE
      nephritis after transplantation may range between 2 and 30%. In most cases
      recurrence is characterized by mild histologic lesions. Only rarely does it lead
      to graft failure. Postransplant immunosuppression does not differ from that used
      routinely. Whenever possible, a steroid-free immunosuppression should be
      scheduled to prevent iatrogenic toxicity in patients who have already received
      long-term steroid treatment. The results of kidney transplantation largely depend
      on the clinical conditions at transplantation. In patients with poor clinical
      status or receiving an aggressive immunosuppression it is advisable to postpone
      the transplant. When some selection criteria are respected, the results of renal
      trasplantation in SLE patients are at least as good as in other transplant
      recipients.

PMID- 15732297
TI  - An epidemiologic review on occupational sleep research among Japanese workers.
AB  - Epidemiologic sleep research on Japanese workers has been increasing in recent
      years. It is timely to give an overview of the sleep issues facing the Japanese
      working population by reviewing the accumulated epidemiological evidence, which
      will contribute to the promotion of a sound occupational health policy and the
      development of occupational sleep research in epidemiology. This paper reviews 24
      studies, 13 for non-shift and 11 for shift Japanese workers, identified by using
      MEDLINE and Japan Cetra Revuo Medicina. The results reviewed are as follows: 1)
      the prevalence of insomnia and other sleep problems is substantially varied, 5 to
      45% for non-shift and 29 to 38% for shift workers, 2) poor sleep quality is
      related to health, occupational activities and personal relations, 3) the risk or
      associated factors are identified in pathophysiology (e.g., hypertension),
      lifestyle behaviors (e.g., diet, alcohol, tobacco), job-related conditions (e.g.,
      job stress, social support, job dissatisfaction, workload, shift schedules) and
      psychopathology (e.g., depressed mood). The methodological limitations found in
      the studies and the strategies of future epidemiologic sleep research in workers
      are discussed.

PMID- 15732298
TI  - Socioeconomic impact of insomnia in working populations.
AB  - To determine whether insomnia impact the professional life of patients and have
      an economical weight, this review article focused on the socioeconomic impacts of
      sleep related problems in working populations. The goal is to summarise the work
      that has been accomplished in that field. Several occupational factors have an
      impact on insomnia: the work schedules (shift work and night work), the physical
      environment at work and the occupational stressors. Insomnia is also a common
      problem in daytime workers. The daytime functioning of insomniacs is a key point
      to understand the impact of insomnia on workers. Absenteeism is one major target
      in the evaluation of severe insomnia at the workplace. Most of the studies find a
      higher rate of work accidents in insomniacs. The economic impact is severe in
      term of direct and indirect costs. Insomnia is a common problem at the workplace.
      The negative impact is not only on individual but also at the societal levels.
      More epidemiological studies appear warranted to demonstrate a reciprocal link
      between work conditions and sleep disorders.

PMID- 15732299
TI  - Shiftwork: safety, sleepiness and sleep.
AB  - This brief paper reviews the available published literature on shiftwork and
      safety that allows the relative risk of "accidents" or injuries associated with
      specific features of shift systems to be estimated. Three main trends in risk are
      discussed, namely that (i) risk is higher on the night shift, and to a lesser
      extent the afternoon shift, than on the morning shift, (ii) risk increases over a
      span of shifts, especially so if they are night shifts, and (iii) risk increases
      with increasing shift length over eight hours. We discuss that some of these
      trends are not entirely consistent with predictions derived from considerations
      of the circadian variations in sleep propensity or rated sleepiness, and consider
      factors relating to sleep that may underlie the observed trends in risk. Finally,
      the practical implications of the trends in risk for the design of safer shift
      systems are discussed.

PMID- 15732300
TI  - The nighttime nap strategies for improving night shift work in workplace.
AB  - Nighttime napping is an effective measure to prevent adverse effects due to night
      shift work. A characteristic of nighttime nap is that it can result in
      considerably deeper sleep. Several studies have shown that taking nighttime naps
      suppressed increasing sleepiness, decreasing alertness during the period
      following awaking from a nap, and prevented disturbance of circadian rhythm
      ("anchor sleep"). The length of daytime sleep after night shift, when combined
      with a nighttime nap, is shorter than that without nap. This finding might be
      interpreted as a beneficial effect rather than a negative feature because workers
      can then spend time engaged in other activities rather than sleeping.
      Nevertheless, the introduction of nighttime sleep break in the workplace has not
      been widely accepted. To promote nighttime napping strategy in the workplace,
      consensus building while acting on conflicting interest is essential. Recently,
      participatory method for improvement of working condition has expanded worldwide.
      A characteristic of the activity is using action checklist and group work, and
      heightening motivation to improvement working condition between worker and
      manager. Through the activities, nighttime napping strategy would be spread more
      in the workplaces and play a role as one of the effective tools for improving
      working conditions, work performance and safety in the future.

PMID- 15732301
TI  - Sleepiness of occupational drivers.
AB  - Drowsiness and sleeping at the wheel are now identified as the reasons behind
      fatal crashes and highway accidents caused by occupational drivers. For many
      years, fatigue has been associated to risk of accidents but the causes of this
      symptom were unclear. Extensive or nocturnal driving was associated to accidents
      but few reports differentiated fatigue from sleepiness. In the early nineties,
      epidemiological data started investigating sleepiness and sleep deprivation as
      cause of accidents. Sleepiness at the wheel, sleep restriction and nocturnal
      driving have been incriminated in 20% of traffic accidents. Drugs affecting the
      central nervous system (i.e., narcotic analgesics, antihistamine drugs),
      nocturnal breathing disorders and narcolepsy have been also associated with an
      increasing risk of accidents. Treatments improving daytime vigilance (i.e., nasal
      Continuous Positive Airway Pressure) reduce significantly the risk of traffic
      accidents for a reasonable economical cost. Sleep disorders among occupational
      drivers need to be systematically investigated. Chronic daytime sleepiness is
      still under diagnosed and sleep disorders (i.e. obstructive sleep apnea syndrome)
      are not enough explored and treated in this exposed population of sedentary
      males. Drivers education and work schedules integrating notions of sleep hygiene
      as well as promotion of sleep medicine could significantly improve road safety.

PMID- 15732302
TI  - Light treatment and circadian adaptation to shift work.
AB  - Work at unconventional hours can have both long and short term consequences.
      Shift workers are often required to perform their duties at times that are not
      favoured by the body's endogenous clock, or circadian pacemaker. A typical night
      shift worker, for example, may report reductions in alertness and performance
      during shifts, or significant difficulty attaining sleep of recuperative value in
      the day, all the while being more likely to develop health complications. The
      study of circadian physiology has significantly contributed to our current
      ability to aid the shift worker deal with atypical schedules. We discuss the
      usefulness of light treatment as a countermeasure for maladaptation to atypical
      work schedules.

PMID- 15732303
TI  - Imbalance between the reality of sleep specialists and the demands of society in
      Japan.
AB  - In contrast to the fruitful achievements of sleep research, sleep medicine has
      never been properly defined and recognized in Japan. Therefore, it is difficult
      for any clinician to have a united view as to what constitutes a sleep
      specialist. The United States (US) has set up sleep medicine as a comprehensive
      clinical specialty connected with various medical, psychological, scientific and
      social fields, having sleep physiology that is methodologically represented by
      polysomnography as a common language. The US system around a core of sleep
      disorders centers and sleep specialists armed with a comprehensive knowledge of
      sleep and sleep disorders can not only diagnose and treat patients with sleep
      disorders, but are also sensitive to the various sleep-related problems at the
      work place such as circadian related safety issues and productivity. Daytime
      sleepiness is dangerous in some situations for the individual as well as society.
      Although this safety issue is an urgent demand in every workplace, sleep medicine
      has not matured nor established enough to respond to it in Japan. Together with
      advancement of sleep research, the sleep medicine community should do everything
      in its power to establish sleep medicine as a practical patient-based clinical
      field.

PMID- 15732304
TI  - Screening for sleep-disordered breathing at workplaces.
AB  - Sleep-disordered breathing (SDB) is a condition of repetitive episodes of
      decreased or arrested respiratory airflow during sleep. Many workers over the
      world remain undiagnosed and untreated for SDB, and leaving themselves at the
      high risk for accidents and cardiovascular disease. Since, the Japanese Ministry
      of Land, Infrastructure and Transport distributed the sleep apnea syndrome manual
      together with sending an official notice to relevant bodies in all over Japan in
      March, 2003, employees and employers are expected to co-operate to prevent SDB
      related accidents at work. We have conducted several surveys using the pulse
      oximetry to detect SDB in working populations and found the high prevalence of
      SDB among workers in Japan, as many as in the US and EU countries. The proper use
      of the result from the screening for SDB seems to be beneficial both to workers
      and employers by maintaining occupational safety and by preventing future
      development of cardiovascular disease.

PMID- 15732305
TI  - An occupational health physician's report on the improvement in the sleeping
      conditions of night shift workers.
AB  - This paper reviews briefly our research findings on sleep and health for shift
      workers at a bakery and a dish factory and aims to give some information on
      health protection with improved sleep. Our medical examinations revealed that
      rises in blood pressure (BP) were frequently observed in male bakery workers on
      the fixed night shift. They took a two-hour nap from 1:00 to 3:00 during the
      night shifts according to our advice. As a result, their diastolic BP
      significantly decreased in subsequent years. Women working shifts before 3:00 at
      a dish factory seemed to show more sleep disturbance, higher daytime sleepiness,
      and more fatigue than those working shits from 3:00. Total sleep hours taken
      during the daytime was similar between two groups. Among the dish, factory
      workers who switched to midnight or night shifts, 70% reported slow recovery from
      fatigue and 30% felt deteriorated health. These women also reported increased
      efforts to obtain a deep sleep, probably making up for shortened sleep.
      Occupational physicians can act to improve shift work conditions through
      monitoring the health of workers, applying naps, and designing possible schedules
      to secure deep, sufficient sleep.

PMID- 15732306
TI  - Fatigue and the criminal law.
AB  - Fatigue is an increasingly recognised risk factor for transportation accidents.
      In light of this, there is the question of whether driving whilst fatigued should
      be a criminal offence. This paper discusses the current legal position, including
      the problems of voluntary conduct and self awareness. Three models for reform are
      proposed. The manner in which scientific research can inform legal consideration
      and future directions for research are discussed.

PMID- 15732307
TI  - International research needs for improving sleep and health of workers.
AB  - Research needs in identifying preventive measures dealing with working time
      arrangements and associated sleep problems are reviewed. These needs are based on
      the recognition of a range of risk factors for health involving disturbed
      circadian rhythms leading to various levels of sleep deficits. The review takes
      account of recent joint change approaches that address both working time
      arrangements and various relevant intervening factors. As examples of such
      approaches, voluntary industry-based guidelines for improving shift work are
      examined. Also reviewed is evidence indicating the effects of improved working
      time arrangements and sleep hygiene on the tolerance of workers working irregular
      shifts. Trends in action-oriented risk assessment are further discussed as the
      effects on health and sleep of these workers may be modified by complex aspects
      related to working situations, family and social conditions, personal
      characteristics and social support. Generally relevant are not only the
      relationships between sleep-affecting factors and health, but also advances in
      taking the various support measures. The effective use of participatory steps is
      found important in dealing with working time arrangements and associated health
      and sleep problems together. It is thus considered important to study (a) the
      efficacy of joint change approaches addressing complex sleep and health factors,
      (b) effective procedures for action-oriented health risk assessment in various
      work life situations, and (c) the relevance of innovative participatory steps to
      improving health and tolerance of workers. Future research topics mentioned by
      the participants of the international symposium on night and shift work held in
      Santos in 2003 are presented, and international efforts to promote research into
      these aspects in field conditions are discussed. Interactive research involving
      local people appears crucial.

PMID- 15732308
TI  - The future of work hours--the European view.
AB  - In Europe the way work hours are handled varies between different countries.
      However, there are some issues that dominate the discussion in Europe and seem
      representative for what is happening. One such is the reduction of working hours-
      which was attempted in several countries but which now seems to be backfiring-
      probably related to the competition from countries outside Europe. Another area
      is compressed work hours--the drive towards maximizing the hours per work day in
      order to increase the number of days off. The health effects are debated--some
      find clear positive effects. A third area is company oriented flexible work
      hours, permitting the employer to make moderate changes in work hours when
      needed. The health impacts have not been evaluated but the loss of individual
      influence at work is obvious. In some parts of Europe self-determined work hours
      have been tried with very positive effects. The EU work hour directive is
      intended to provide uniformity but permits a counterproductive "opting out",
      creating problems of imbalance.

PMID- 15732309
TI  - Toward better sleep for workers: impressions of some needs.
AB  - We know there are persons exposed demanding work schedules and sleep loss in
      almost every occupation or industry, but we still need better population-based
      information on how many sleepy or inattentive workers there are, where they are,
      and to what extent they are a risk to themselves or others. The absence of such
      information, however, does not prevent us from continuing to conduct worksite
      interventions and demonstrations that will produce good, evidence-based
      guidelines to help workers and workplace administrators make informed choices
      about sleep and provide optimal conditions for sleep. In addition, systematic
      study and publication of how managers and policy-makers accept our research to
      make worksite changes, and what factors beside our research influence their
      decisions, would contribute techniques to the greater public health community
      aiming to translate research results into good practice.

PMID- 15732310
TI  - Sleep-related risk of occupational injuries in Japanese small and medium-scale
      enterprises.
AB  - A cross-sectional study evaluated the contribution of daily sleep habits to
      occupational injuries. A self-administered questionnaire solicited answers about
      sleep, symptoms of depression, occupational injury, demographics, presence of
      diseases and lifestyle factors from 2,903 workers between the ages of 16-83 (mean
      45) yr in small and medium-scale enterprises. Eight sleep habits were queried and
      dichotomized: 1) less or more than 6 hr of daily sleep, 2) taking more or less
      than 30 min to fall asleep (Difficulty initiating sleep; DIS), 3) awakening
      during sleep more or less than 3 times/wk (Difficulty maintaining sleep; DMS), 4)
      early morning awakening more or less than 3 times/wk (EMA), 5)
      definitely/somewhat difficulty waking up or not, 6) sleeping very poorly/not so
      well at night or not, 7) definitely/somewhat insufficient nightly sleep or not,
      and 8) difficulty in breathing during sleep more than once/week or less.
      Occupational injury was assessed by asking subjects 'Have you ever been injured
      during your work, including minor scratches and cuts (Yes/No)?' Both sleep and
      injury were assessed over the previous one year period. One-third of workers
      answered that they had experienced injury. Workers with sleep features of DIS,
      sleeping poorly at night, insufficient sleep, and insomnia had a significantly
      higher prevalence for injury after adjusting for multiple confounders. The
      findings suggest that poor nocturnal sleep habits are associated with self
      reported occupational injury.

PMID- 15732311
TI  - How well do train driver's sleep in relay vans?
AB  - Relay working operations typically require two crews of train drivers to work a
      rotating 8-h schedule for two or more days. While one crew is driving, the other
      has the opportunity to sleep onboard the train. The current study investigated
      the impact of relay work on drivers sleep quantity and quality. Fourteen drivers
      wore wrist activity monitors and completed sleep/wake diaries for 3 d prior to
      and during short (<48 h) relay trips. Drivers obtained an average of 7.8 h sleep
      per night while at home, and an average of 4 h sleep per opportunity during the
      relay trip. Sleep obtained in the relay van was associated with longer sleep
      onset latencies, lower efficiency and poorer subjective quality than sleep at
      home. During the relay trip, drivers obtained significantly more sleep during
      opportunities that occurred in the evening, than those that occurred early
      morning or during the day. These findings suggest that while drivers are able to
      obtain sleep during short relay operations, it is of poorer quality than sleep
      obtained at home. Further, the timing of the sleep opportunities during the relay
      trip impacts on the quantity and quality of sleep obtained.

PMID- 15732312
TI  - The impact of extended leave on sleep and alertness in the Australian rail
      industry.
AB  - In the past, scientific studies have investigated the effects of shift timing and
      duration on sleep and alertness in the rail industry. To our knowledge no
      research has been conducted to determine the effects of extended break lengths
      (>48 h) on these factors. Hence, this study analyses the work and rest schedules
      of 304 Australian rail employees (mean age 41.3 yr, standard deviation 7.4 yr) to
      determine the effect of prior break lengths (12-169 h) on sleep and subjective
      alertness at work after periods of leave. Extended break periods (>48 h) were
      found to increase the length of the sleep prior to returning to work and reduce
      the total wake time to the end of the first shift, but did not influence levels
      of subjective alertness immediately prior to the commencement of the first shift.
      Research into the influence of longer break periods (>169 h) is needed in order
      to make definitive conclusions regarding sensible return to work policies after
      extended leave within the Australian rail industry.

PMID- 15732313
TI  - Sleepiness in various shift combinations of irregular shift systems.
AB  - The present study examined the occurrence of sleepiness in various shift
      combinations ending with a night or morning shift. Three weeks' sleep/work shift
      diary data, collected from 126 randomly selected train drivers and 104 traffic
      controllers, were used in statistical analyses. The occurrence of sleepiness at
      work (i.e., Karolinska Sleepiness Scale 7 or higher) was tested with a
      generalised linear model with repeated measurements including explanatory factors
      related to shifts, sleep, and individual characteristics. The prevalence of
      severe sleepiness varied between 25% and 62% in the combinations ending with a
      night shift and between 12% and 27% in the combinations ending with a morning
      shift. The occurrence of sleepiness did not, however, systematically vary between
      the shift combinations in either case. An increased risk for sleepiness was
      associated with high sleep need and long shift duration in the night shift and
      with high sleep need, short main sleep period, long shift duration and an early
      shift starting time in the morning shift. Also having a child was associated with
      an increased risk for sleepiness in the night shift. The results suggest that the
      shift history of 24-36 h prior to the night and the morning shift is not strongly
      associated with the occurrence of sleepiness at work, but there are other
      factors, such as shift length and starting time and sleep need, that affect a
      risk for sleepiness at work.

PMID- 15732314
TI  - Self-report naps in irregular work schedules.
AB  - Few studies have examined napping in irregular work schedules such as those
      experienced by freight locomotive engineers. The current study examined the
      effect of napping in irregular work schedules on sleep length and three
      subjective measures: ability to go to sleep, ability to stay asleep, and a
      feeling of being well-rested upon awakening. One hundred and seventy-nine freight
      engineers completed a 14-d activity log, providing information on sleep times and
      subjective evaluations of sleep. The results indicated that days with naps
      resulted in significantly more total sleep but less sleep in the main sleep
      period of the day. The days with naps also resulted in somewhat more difficulty
      with going to sleep, staying asleep and with feeling well-rested upon awakening.
      It is important to note, however, that when examining the days with naps, nap
      length was not significantly correlated with main sleep time, ability to go to
      sleep, ability to stay asleep, or feeling well-rested upon awakening. These
      results suggest that napping may be useful when working irregular work schedules
      if the engineer is willing to accept a slight decrease in ability to go to sleep,
      stay asleep, and feeling rested.

PMID- 15732315
TI  - Sleep deprivation in junior doctors--house officers in Singapore.
AB  - House officers are known to endure marked levels of sleep deprivation in
      administration of their duties. We aim to establish sleep patterns of local house
      officers while on the job and the impact it might have on their mood and
      sleepiness state. We also studied their sleep during their final year of medical
      school and pre-university for identification of any prior sleep deprivation.
      Questionnaires were used to assess sleep and mood change. Sleepiness levels on
      the day after call were assessed using the Stamford Sleepiness Scale. Subjects
      were found to sleep a median of only 1.0 (+/- 2.0) h per night on call and 6.0 h
      (+/- 1.0) per non-call night. They suffered median of 5 interruptions (+/- 5)
      during sleep on one night call. Night call was found to adversely affect mood in
      89.5% of the subjects while daytime sleepiness levels following call were found
      to increase the more the time spent at work after call. Subjects were found to
      have had 6.5 h (+/- 1.0) of sleep per night during final year of medical school
      and 8.0 h (+/- 1.0) in final year of pre-university. House officers enter the
      profession chronically sleep-deprived. The call schedule and general work regime
      further add to the existent sleep deprivation and may have adverse consequences
      on patient care and doctor's health. This calls for measures to be instituted for
      provision of proper sleep and work hours for them.

PMID- 15732316
TI  - Associations of sleep problems and recent life events with smoking behaviors
      among female staff nurses in Japanese hospitals.
AB  - For the purpose of examining the relation of sleep problems and other possible
      correlates with smoking among staff nurses in hospitals, the cross-sectional data
      of a self-administered questionnaire survey for 522 Japanese female staff nurses
      were reanalyzed. Registered nurses or licensed practical nurses were 82%, while
      nursing assistants were 18%. The prevalence of current smoking (PCS) was 29%,
      being higher than that in the general population of Japanese women. The current
      smokers exhibited a high tendency toward tobacco dependence. Multivariate
      analyses revealed that PCS was associated with recent frequent night shifts and a
      large amount of support from coworkers, while the association of a large amount
      of job control and a feeling of light overnight sleep with PCS was also
      suggested. The tobacco-dependent tendency was associated with recent life events
      and the presence of insomnia. It is possible that smoking is a countermeasure
      against sleepiness caused by the disadaptation to shift-work, or that tobacco
      intake pharmacologically disturbs sleep. For decreasing PCS in staff nurses,
      further research should focus on the relation of smoking with their sleepiness
      and shift-working system, and also on the process in which major life events
      develop smoking behaviors.

PMID- 15732317
TI  - Actual conditions of work, fatigue and sleep in non-employed, home-based female
      information technology workers with preschool children.
AB  - We conducted a study on time budget and fatigue feelings over a two-month period
      of 12 non-employed, home-based female workers using computers (mean age 35.2 yr).
      All of them had at least one preschool child. The actual amount of work done by
      these women and the related effects on the fatigue feelings and sleep were
      investigated. The results showed that the work done was characterized by
      involving many night hours, irrespective of the day of the week. The degree of
      subjective fatigue was not dependent on the number of hours worked, but affected
      by the time at which the work of the day was completed. This tendency was notable
      after one o'clock in the morning when the work was completed. Those who followed
      such a work pattern took daytime naps, although a quality of the subsequent
      nighttime sleep taken might be poor. They took a nap around 14:00 but not around
      19:00. The sleep strategies were thus shown to be affected by home-based work. A
      need is suggested to support these workers in adjusting work time distribution
      and taking sleep patterns adapted to individual conditions.

PMID- 15732318
TI  - Shiftwork locus of control, situational and behavioural effects on sleepiness and
      fatigue in shiftworkers.
AB  - A number of situational and behavioural individual differences moderate the
      impact of shift and night work. The aims of this study were to identify
      individual differences correlates of sleep and fatigue-related shiftwork outcomes
      and examine their potential relative causal impact. Power company shiftworkers
      completed a questionnaire that measured age/experience, number of dependents,
      shiftwork locus of control, morningness-eveningness, workload and sleep/health
      related behaviours. Shiftwork sleep and fatigue outcome variables were also
      measured. Hierarchical multiple regression was used to examine predictive
      contributions of the individual difference variables and to generate path
      coefficients from situational and psychological predictors through behavioural
      variables to the outcome variables. Shiftwork-specific internality showed the
      most systematic significant causal relationships with sleep and fatigue outcomes.
      While not having as strong a direct causal influence on sleep and fatigue
      outcomes as internality, the other predictors did show more significant causal
      effects upon sleep-related behaviours than did internality. Behavioural variables
      made little contribution to the total causal effects of the predictors on the
      outcome variables. The results suggest control beliefs to be a moderating factor
      in shiftwork exposure and the potential utility of this construct in aiding more
      effective targeting of interventions.

PMID- 15732319
TI  - Modifying effects of perceived adaptation to shift work on health, wellbeing, and
      alertness on the job among nuclear power plant operators.
AB  - This study examined the relationship between perceived adaptation to shift work
      and shift-related problems. A total of 608 male operators at nuclear power plants
      completed a set of validated questionnaires including a modified version of the
      Standard Shiftwork Index, which covered adaptation to shift work, fit to job
      content, chronotypes, chronic fatigue, sleep, naps, shift work locus of control
      (SHLOC), psychological health, social/family life, daytime sleepiness, workload,
      alertness on the job, and lifestyle factors. Participants were divided into two
      groups according to their perceived level of adaptation to shift work. The good
      adaptation group showed better outcomes than the poor adaptation group in terms
      of fit to job content, chronic fatigue, daytime sleep before night shifts, social
      and family disruption, SHLOC, psychological health, and alertness during night
      shifts (ps<0.001). Operators who reported good adaptation also took a more
      frequent, longer nap and more cigarettes during night shifts (ps<0.05). The cross
      sectional study design cannot determine a causal relationship between perceived
      adaptation and shift work problems, yet the present results suggest that the
      effects of working shifts may be modified by perceptions of shift work
      adaptation.

PMID- 15732320
TI  - Self-awakening prevents acute rise in blood pressure and heart rate at the time
      of awakening in elderly people.
AB  - Self-awakening, waking up at a designated time decided before sleeping, could
      prevent failure in the blood circulation vessel system such as heart attack,
      acute increases in heart rate or blood pressure upon waking. Previous research
      showed that anticipatory changes occurred in heart rate prior to awakening from a
      short nap by means of self-awakening for young participants. However, the effects
      of self-awakening remained unclear for elderly people. The present study examined
      the effects of self-awakening on heart rate and blood pressure in a short
      afternoon nap (20 min) among the elderly. Nine participants [74.1 (SD = 5.01)
      years old] underwent both self-awakening and forced-awakening conditions. In the
      self-awakening condition, it was revealed that blood pressure gradually increased
      before the scheduled time of awakening, and that heart rate did not show a rapid
      increase at arousal. In contrast, forced-awakening induced acute increases in
      both heart rate and blood pressure. These results suggest that self-awakening
      facilitates a more smooth transition from sleep to wakefulness via autonomic
      activation before the time of self-awakening.

PMID- 15732321
TI  - The impact of sustained wakefulness and time-of-day on OSPAT performance.
AB  - Fatigue associated with shiftwork is a key contributor to human error in the
      workplace. One way to prevent fatigue-related errors from occurring is to
      identify fatigue in employees using fitness-for-duty measures. The Occupational
      Safety Performance Assessment Test (OSPAT), an unpredictable tracking task that
      measures hand-eye coordination, is currently being used as a fitness-for-duty
      measure in a variety of industries, but has not yet been validated as a test
      sensitive to the effects of fatigue. Consequently, the aim of this study was to
      systematically examine the impact of sustained wakefulness and time-of-day on
      OSPAT performance. Twenty individuals (10 male, 10 female), aged between 18-25 yr
      (M=20.90, SD=2.29) participated in the study, which was conducted in Australia.
      The study had a repeated measures design, whereby participants completed the
      OSPAT and measures of sustained attention (i.e., the psychomotor vigilance task:
      PVT), and subjective alertness (i.e., the Visual Analog Scale: VAS) every 2 h
      during 24 h of sustained wakefulness, beginning at 07:00 h. Results revealed that
      VAS ratings of alertness, PVT performance, and OSPAT performance declined
      significantly as hours of wakefulness increased during the night-time (all
      p<.01). Furthermore, a positive correlation between OSPAT and PVT performance was
      observed (r=0.40, p<.01). Overall, these findings suggest that OSPAT is sensitive
      to sustained wakefulness during the night-time, and builds the case for OSPAT
      being a suitable measure for determining fitness-for-duty in workplace
      environments.

PMID- 15732322
TI  - Changes in the concentration of urinary 6-sulphatoxymelatonin during a week of
      simulated night work.
AB  - The aim of the study was to examine the adaptation of participants to a common
      night work schedule using urinary 6-sulphatoxymelatonin (aMT6s) concentration as
      the circadian phase marker. Fifteen adults (7 male, 8 female, age = 21.9 yr)
      spent nine consecutive nights in the laboratory, including: (i) adaptation sleep,
      (ii) baseline sleep, and (iii) seven simulated night shifts (23:00-07:00 h)
      followed by daytime sleep. During the baseline and daytime sleeps, participants
      collected urine samples which were subsequently assayed for aMT6s. The
      concentration of aMT6s in urine for the first three day sleeps was significantly
      lower than for the baseline sleep, but there was no difference in aMT6s
      concentrations between any of the last three day sleeps and the baseline sleep.
      The data indicate that people may adapt to a pattern of work that includes seven
      consecutive night shifts if they adhere to a fixed sleep schedule, if their
      exposure to morning sunlight is minimised, and if they are provided with an ideal
      sleep environment.

PMID- 15732323
TI  - A National Sleep Foundation's conference summary: the National Summit to Prevent
      Drowsy Driving and a new call to action.
AB  - On November 20-21, 2002, the National Sleep Foundation (NSF), a U.S.-based non
      profit organization, and a coalition of other organizations, federal agencies and
      corporations convened a National Summit to Prevent Drowsy Driving at the National
      Academy of Sciences in Washington, DC. The Summit brought together experts in the
      fields of transportation, safety and health, sleep research, and communications
      as well as advocates to assist in the creation of a comprehensive national agenda
      to increase awareness about the dangers of drowsy driving. Recommendations from
      the Summit formed the basis of post-summit activities, including the development
      of a new Web site (www.drowsydriving.org) dedicated to the prevention of driver
      fatigue and a report, the National Action Plan to Prevent Drowsy Driving, which
      describes a series of action items for national, state and local initiatives in
      the areas of research, public policy, and educational programs.

PMID- 15732324
TI  - Improving health, safety, and profits in extended hours operations (shiftwork).
AB  - Circadian Technologies, Inc. (CIRCADIAN) is an international consulting firm that
      for over 20 yr has helped employees better cope with shiftwork, while ensuring
      their employers reduce costs and maximize profits. This paper describes two of
      the methods employed to reduce accidents, absenteeism, and turnover, while
      improving morale and productivity in extended hour operations (shiftwork).
      Shiftworkers rarely receive on-the-job training to help them cope better with the
      rigors of working nights, evenings, and early mornings. A pre- and post-training
      study by CIRCADIAN demonstrated improvements in health and fatigue indices, and
      an increase in daytime sleep length. Companies who provide shiftwork lifestyle
      training also have lower rates of absenteeism and turnover compared to companies
      that do not provide training. The second intervention described in this paper is
      a novel method of shift scheduling. There are thousands of potential schedules,
      so how does a company choose the best schedule for their facility? The answer
      lies in allowing employees to be involved in the process of selection. This
      results in a workforce that experiences less fatigue, turnover and absenteeism,
      and higher morale.

PMID- 15732325
TI  - The Napping Company: bringing science to the workplace.
AB  - Increasing emphasis is currently being given to the importance of bringing
      knowledge gained from science into places where people live and work, in order to
      increase the impact science has on the general public's quality of life.
      Scientific findings about the positive impact of napping on mood and performance
      are an example of research generated knowledge that needs to be brought to the
      workplace. A major goal of the Napping Company (www.napping.com) is to bring the
      science of napping to the workers and the workplace so that employees and
      employers can act on this knowledge and change worker napping behavior and
      employer napping policies. The present paper overviews the challenges inherent in
      making scientific knowledge useful to how we live our lives. The Napping Company
      is guided by five principles of knowledge transfer in the company's attempts to
      disseminate and increase utilization of napping research. Examples are given to
      illustrate how the Napping Company has used these principles to bridge the gap
      between napping science and nap behavior and policies in the workplace.

PMID- 15732326
TI  - The effect of heating on the dissolution of alkaline earth silicate fibers in a
      simple amino acid solution and water.
AB  - In order to evaluate the effect of pre-heating on biosolubility and water
      resistance of alkaline earth silicate (AES) fibers in MgO-SrO-SiO2 and MgO-CaO
      SrO-SiO2 compositions, dissolution experiments of the heat-treated (from 110
      degrees C to 1,260 degrees C) AES fibers have been carried out in a glycine
      solution and in distilled water at 40 degrees C for 50 h. The dissolution
      experiments show that the heat-treatment around 700 degrees C has made the AES
      fibers more soluble in the glycine solution. This is due to the phase separation
      of the AES fibers resulting from the heat-treatment. Probably, alkaline earth
      rich glassy phases formed by the phase separation facilitate the dissolution of
      the heat-treated AES fibers in the glycine solution. The heat-treatment around
      700 degrees C is possible to decrease the toxicity of the AES fibers further.
      Meanwhile, this heat-treatment around 700 degrees C has given little effect on
      the dissolution of the AES fibers in the distilled water. This indicates that the
      resistance of the AES fibers to water or humidity remains unaffected by the heat
      treatment. The water-resistance is a very useful property for MMVFs. This study
      suggests that the heat-treatment around 700 degrees C is probably an useful
      treatment in order to enhance the total performance, biosolubility and water
      resistance, of AES fibers.

PMID- 15732327
TI  - Evaluation of whole-body vibration by the category judgment method.
AB  - The purpose of this research is to establish a scale for comfort with regard to
      whole-body vibration by the category judgment method. Experiments were conducted
      with random signals as stimuli. These stimuli consisted of three types of signal,
      namely stimulus F, with flat PSD (Power Spectrum Density) ranging from 1 to 100
      Hz, stimulus H with PSD, which became 20 dB higher at 100 Hz than at 1 Hz, and
      stimulus L that had a PSD 20 dB lower at 100 Hz. These signals were modified by
      Wk frequency weighting in accordance with ISO 2631-1, and the R.M.S. values were
      adjusted to be equal. In addition, the signal levels were varied over a range of
      five steps to create 15 kinds of individual stimuli. The subjects sat on a flat,
      horizontal metal plate mounted directly on the vibrator and were exposed to
      vertical vibrations before being asked to choose a numerical category to best
      indicate their perceived level of comfort (or otherwise) during each stimulus.
      The creation of this assessment scale, including the aforementioned categories,
      enabled not only clarification of the relationship between the vibration stimuli
      and the degree of comfort but also discovery of the connection between the
      frequency-weighted R.M.S. acceleration and the corresponding categories
      representing each degree of comfort without overlap. Moreover, it became clear
      that the subjects' assessment of the degree of comfort perceived differed with
      differences in the vibration spectrum.

PMID- 15732328
TI  - Comparison of the apparent mass of the seated human measured using random and
      sinusoidal vibration.
AB  - Exposure to whole-body vibration is generally accepted as being a risk factor for
      low back pain and therefore exposure to vibration should be minimised. The
      results of previous laboratory based research investigating the biomechanical
      response of the seated human to vibration has been used to develop models that
      can be used within tools that are capable of predicting the response of seats.
      Several studies in the literature have reported apparent masses of seated human
      subjects whilst exposed to either random or sinusoidal vibration. Although these
      studies have shown similar trends, there have been no systematic comparisons of
      apparent mass for the same subjects exposed to random and sinusoidal vibration.
      This paper reports a study where twelve male subjects were exposed to random
      whole-body vibration at 1.0 m/s2 r.m.s. and to sinusoidal vibration at 1, 2, 4,
      8, 16 and 32 Hz. The modulus of the apparent masses were nominally identical when
      measured using random or sinusoidal vibration. The phase of the apparent masses
      were similar at 1, 2 and 4 Hz, when measured using random or sinusoidal
      vibration, but showed consistent differences at 8, 16 and 32 Hz. As the results
      between experiments using different waveforms are similar, models derived from
      experimental work based on one type of stimulus could be applied in scenarios
      involving the other type of stimulus.

PMID- 15732329
TI  - Biodynamic response at the palm of the human hand subjected to a random
      vibration.
AB  - This study investigated the biodynamic response (BR) distributed at the palm of
      the hand subjected to a random vibration. Twelve male subjects were used in the
      experiment. Each subject applied three coupling actions (grip-only, push-only,
      and combined grip and push) on a simulated tool handle at three different levels
      (50, 75, and 100 N) of palm force. This study found that the hand-arm system
      resonated mostly in the frequency range of 20 to 50 Hz, depending on the specific
      test treatment and individual characteristics. The maximum vibration power
      transmission through the palm occurred at the resonant frequency. Increasing the
      effective palm force generally increased the BR magnitude and resonant frequency.
      The apparent stiffness measured at the middle frequencies (80-100 Hz) is
      correlated to the BR in almost the entire frequency range (20-1,000 Hz). Under
      the same palm force, the push-only action corresponded to the highest BR values
      while the grip-only action generally produced the lowest values. Since the
      resonant frequency range matches the dominant vibration frequency range of many
      percussive tools, it is anticipated that the palm BR and vibration power
      transmission may have an association with vibration-induced injuries or disorders
      in the wrist-arm system among the workers using these tools.

PMID- 15732330
TI  - Relationship between chest X-ray findings and pulmonary function tests in dust
      workers.
AB  - Occupational injuries are decreasing due to the improvement in occupational
      management in the workplace in recent years. However, pneumoconiosis and its
      complications remain important occupational diseases. Based on the report 'survey
      on classification for supervision of pneumoconiosis in Japan' performed in 1994,
      this study compared age, number of years at the job and pulmonary function tests
      among work types, and examined the characteristics of cases in which pulmonary
      function results were worse than expected from the chest X-ray findings. In the
      comparison among work types, mean age was higher and %VC was lower among workers
      exposed to silica or asbestos, and FEV1.0% appeared to be lower among silica
      exposed workers. Multiple regression analysis showed that silica or asbestos
      exposed work environments strongly affected %VC. Some cases showed dissociation
      between the X-ray findings and pulmonary function tests, which appeared to be
      caused by certain types of work environments. In this study, all the subjects had
      findings of pneumoconiosis in their chest X-ray. It is necessary to perform a
      longitudinal survey on pneumoconiosis-free subjects to clarify the precise
      association of lung function tests with chest X-ray.

PMID- 15732331
TI  - [Laparoscopic unroofing of peripelvic cyst].
AB  - Laparoscopic unroofing of renal cyst has replaced open surgical intervention in
      recent years. We report our experience with this procedure on 6 patients with
      hydronephrosis due to peripelvic cyst. Four male and two female patients, ranging
      from 51 to 67 years, underwent laparoscopic unroofing of peripelvic cyst. All
      patients had various degrees of hydronephrosis. Two patients had lumbago and
      hematuria. The cause of this hematuria was probably due to the renal pelvic
      stone. Surgical approaches i.e., retro- or transperitoneal were selected
      depending on the location of cyst. The operative time ranged from 80 to 235
      minutes (mean 167 minutes). The length of postoperative hospital stay ranged from
      3 to 7 days (mean 4.6 days). Intraoperative blood loss ranged from 20 to 26 cc
      (mean 21 cc). Four weeks after the operation, all patients showed improvement of
      hydronephrosis. Laparoscopic unroofing of peripelvic cyst is a safe and
      efficacious procedure, and could be an' attractive alternative for management of
      peripelvic renal cysts.

PMID- 15732333
TI  - [Clinical result of testicular sperm extraction (TESE) to male-factor infertility
      in Toyota Memorial Hospital].
AB  - Owing to progress of assisted reproduction technology in recent years, it has
      become possible for couples with infertility problems to have children. Between
      March 1998 and May 2003 testicular sperm extraction (TESE) was performed on 30
      men with male-factor infertility in our hospital. Consequently, we succeeded in
      recovering 20 spermatozoa. Intracytoplasmic sperm injection was subsequently
      performed in 15 couples and resulted in 8 pregnancies. There was a statistically
      significant difference in follicle-stimulating hormone, luteirizing hormone and
      Johnsen's score between the non-obstructive groups with successful TESE and those
      with unsuccessful TESE.

PMID- 15732332
TI  - [Combination chemotherapy with docetaxel and cisplatin in patients with hormone
      refractory prostate cancer].
AB  - We investigated the efficacy of docetaxel and cisplatin for hormone-refractory
      prostate cancer (HRPC). Thirteen patients with HRPC were treated with 30 mg/m2
      docetaxel weekly for 3 weeks and 70 mg/m2 cisplatin on day 1. Treatment was
      repeated every 21 days. They received 2 cycles and were evaluated for the
      responses to serum prostate-specific antigen (PSA) and tumor size. Ten (77%) of
      the 13 patients showed a 50% or greater decrease in PSA with a median time to
      progression of 3 months. One of the 2 patients with measurable soft tissue
      disease showed a reduction in disease. No severe toxicity of this regimen was
      observed. Combination chemotherapy with docetaxel and cisplatin in patients with
      HRPC was well tolerated and efficatious with a significant decrease in serum PSA
      and measurable disease.

PMID- 15732334
TI  - [Small intestinal metastases from renal cell carcinoma: a case report and
      literature review].
AB  - We report a case of small intestinal metastasis from renal cell carcinoma (RCC)
      in a 57-year-old female. The patient had undergone partial nephrectomy for a
      right RCC (pT1aN0M0) in June 1997. She later developed multiple metastases, in
      the lungs, brain, and bone, and was admitted with nausea, vomiting, and appetite
      loss in April 2003. She presented with melaena a few weeks after her admission
      and a computed tomographic scan revealed a small bowel mass that was not
      definitively diagnosed. We removed the mass surgically, and the histological
      features confirmed the diagnosis as metastatic RCC. The patient recovered and
      could consume, but died of brain metastases 102 days after the surgery.
      Metastasis of RCC in the small bowel is a rare entity clinically. To our
      knowledge, this is only the 20th case of small intestinal metastasis from RCC
      reported in the Japanese and English literature.

PMID- 15732335
TI  - [Renal hemangiopericytoma discovered at a health screening: a case report].
AB  - We report a case of renal hemangiopericytoma which was incidentally discovered by
      ultrasonography at a health screening. A 58-year-old man was admitted to our
      hospital for close examination of the renal tumor. Computed tomography revealed
      the left renal tumor, 60 x 50 mm in size, which was well enhanced with contrast
      medium. Magnetic resonance imaging revealed an isointensity mass (T1-weighted)
      and high-intensity mass (T2-weighted) at the left kidney. Radical nephrectomy was
      performed on suspicion of left renal cell carcinoma. Histopathological
      examination revealed renal hemangiopericytoma. The present case is the 7th in the
      Japanese literature.

PMID- 15732336
TI  - [Multifocal liposarcoma showing rapid growth in a short term: a case report].
AB  - We report a case of multifocal liposarcoma that showed rapid growth in a short
      term. A 65-year-old male was referred from a local doctor to our clinic with the
      chief complaint of abdominal fullness. Abdominal CT shows two huge tumors in the
      intraperitoneal and retroperitoneal space, and we diagnosed it as multifocal
      liposarcoma. Both tumors were resected. The surgical specimens of intraperitoneal
      and retroperitoneal masses were 20 x 10 cm and 12 x 8 cm in size, and 3.5 kg and
      2.8 kg in weight, respectively. Histological diagnosis of both tumors was myxoid
      liposarcoma. However, the tumor recurred 4 months later, and two additional
      operations were required because of rapid growth. The patient died at 7 months
      after the first admission. The clinical outcome of myxoid liposarcoma is known to
      be better than other histological types, but it is very poor when the tumor
      appears multifocally.

PMID- 15732337
TI  - [A case of retroperitoneal bronchogenic cyst].
AB  - A 59-year-old hypertensive man was referred to our hospital with a
      retroperitoneal cystic tumor, measuring 6 cm in diameter that was detected by an
      ultrasound examination during routine check-up 2 years before coming to our
      department. During the 2-year follow-up, the cystic tumor gradually increased in
      size. The patient also became hypertensive with slightly elevated urine levels of
      noradrenaline and dopamine, while the plasma catecholamines and their metabolites
      in the urine were within the normal range. Computed tomographic scanning and
      magnetic resonance imaging revealed a dumbbell-shaped retroperitoneal cyst with
      dense fluid, measuring 7 x 3.5 x 3 cm in diameter, in the left supra-adrenal and
      sub-diaphragmatic regions. He underwent extirpation of the cystic tumor with
      suspicion of adrenal endocrine cystic tumor. The histopathological diagnosis was
      a bronchogenic cyst, which is an extremely rare developmental anomaly in the
      retroperitoneal space. We herein report this rare case of retroperitoneal
      bronchogenic cyst and present a brief review of the previously reported 30
      Japanese cases.

PMID- 15732338
TI  - [Blind-ending bifid ureter: report of a case].
AB  - A case of blind-ending bifid ureter is presented. A 33-year-old woman was
      admitted with the compliant of right flank pain. Drip infusion pyelography and
      retrograde pyelography showed a right blind-ending bifid ureter (about 26 cm in
      length) at a site about 4 cm superior to the right ureteral opening. No treatment
      was needed because her symptoms subsided spontaneously.

PMID- 15732339
TI  - [Neuroendocrine differentiation in adenocarcinoma of prostate during combined
      androgen blockade therapy: a case report].
AB  - Prostatic neuroendocrine (NE) carcinoma is a rare disease with a poor prognosis
      because of its rapid progression and the androgen-independent characteristic, for
      which no successful therapy is available presently. We report a case of NE
      differentiated prostate cancer, which was diagnosed as adenocarcinoma initially
      and progressed with NE differentiation during the combined androgen blockade
      therapy.

PMID- 15732340
TI  - [A case of mycotic spermatic cord abscess in a continuous ambulatory peritoneal
      dialysis patient].
AB  - A 66-year-old male patient has been on continuous ambulatory peritoneal dialysis
      (CAPD) since 1993, and was diagnosed with right hydrocele of the spermatic cord
      in 1998. He repeatedly developed CAPD-related bacterial peritonitis 3 times. In
      February 2001, hemodialysis was prescribed for treatment of mycotic peritonitis.
      A palpable mass was noted in the right inguinal region in October 2001 and a
      computed tomographic (CT) scan disclosed a 4 cm circular lesion with relatively
      low density and thick wall in the right inguinal region. Spermatic-orchiectomy
      was performed. Histological diagnosis was mycosis like Candida on the abscess
      wall. To our knowledge, this is the first case of spermatic cord abscess in a
      CAPD patient in the Japanese literature.

PMID- 15732341
TI  - [Metastatic small intestinal tumor associated with transitional cell carcinoma: a
      report of 2 cases and review of cases in Japan].
AB  - Transitional cell carcinoma (TCC) frequently metastasizes to lymph nodes, liver,
      lungs and bone. However, metastasis to the gastrointestinal tract is rare. We
      report two cases of bladder tumor which metastasized to the ileum. According to
      the literature, these are the 7th and 8th cases in Japan. Case 1: A 87-year-old
      man had a history of bladder tumor (TCC, grade 3, pT2bN0M0) and has transurethral
      resection of bladder tumor (TUR-BT) three times. Two months after the last TUR
      BT, he was admitted with ileus. As computed tomography (CT) showed abdominal free
      air, our diagnosis was perforation of gastrointestinal tract. The patient
      received an operation which resected partial ileum. We found the elastic hard
      tumor in the ileum on the perforated lesion, which showed metastatic TCC in the
      ileum pathologicaly. Case 2 : A 53-year-old man visited our hospital with gross
      hematuria. Cystoscopy showed a non-papillary broad based tumor in the right wall
      of the bladder. CT showed a bladder tumor invaded into the prostate (pT4aN1M0),
      we performed total cyctectomy and ileal conduit after neo-adjuvant chemotherapy.
      During the operation, we found the tumor (2 cm in diameter) in the small
      intestine which was metastasized of bladder tumor.

PMID- 15732342
TI  - [Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary
      bladder].
AB  - A 85-year-old woman presented with macroscopic hematuria and miction pain.
      Cystoscopy revealed a wide-based submucosal mass, and biopsied specimens of the
      mass showed a B-cell lymphoma of the MALT type. Computed tomography (CT) showed a
      7.5 x 3.0 cm solitary mass lesion situated from the anterior wall to the right
      lateral bladder wall, and magnetic resonance imaging (MRI) showed a low intensity
      in T1W1, high in T2W1 without invasion. After she was admitted to our hospital,
      TUR of the lesion was performed. The findings were consistent with extranodal
      marginal zone B-cell lymphoma of the MALT type. No evidence of lymphoma was found
      on the CT of the pelvis, chest X-ray and Gallium scintigraphy. The patient had
      stages I(AE) lymphoma. The patient was treated with radiation therapy to the
      bladder and pelvis (40 Gy in 20 fractions) and was followed with CT every 3
      months. She had no evidence of recurrance.

PMID- 15732343
TI  - [Castleman disease in the pelvic cavity].
AB  - Although Castleman disease may occur in any lymph node of the body, it is the
      most commonly found in the thoracic cavity. Castleman disease rarely occurs in
      the pelvic cavity and only 8 such cases have been reported previously in Japan.
      In this report, we describe a case of Castleman disease in the pelvic cavity. A
      36-year-old man complained of fever. Both serum c-reactive protein (CRP) and
      serum interleukin-6 (IL-6) were elevated. Computed tomography and magnetic
      resonance imaging showed a solid mass with calcification in the pelvic cavity.
      The pelvic mass was surgically excised. The removed mass was solid and 75 x 45 x
      30 mm in size. The histological diagnosis was the plasma cell type of Castleman
      disease. Fever subsided and both serum CRP and serum IL-6 were normalized after
      the operation. No evidence of disease was detected one year post operation.

PMID- 15732344
TI  - [Vesicorectal fistula caused by pelvic metastasis of penile cancer: a case
      report].
AB  - A 65-year-old man was referred to our hospital complaining of glans induration.
      Tumor biopsy revealed squamous cell carcinoma. Although he was given radiation
      therapy and subcutaneous injection therapy of bleomycin, viable cancer cells
      remained. Then he was given combination chemotherapy of bleomycin and cisplatin,
      and paint therapy of bleomycin ointment. Local recurrence with a cauliflower-like
      tumor occurred five years after the chemotherapy. Then we performed total
      penectomy and reconstructive surgery of penis. Five years later, discharge of
      urine from anal appeared. Computerized tomography of pelvis demonstrated a mass 3
      cm in diameter in the anterior portion of anal and cystogram demonstrated a
      vesicorectal fistula. We tried to perform fistulectomy, but foiled because of
      large fistula. Then we inserted a urethral catheter, which resulted in
      obstruction of fistula by its balloon, and we made a cystostomy for securing
      urinary tract. Pathological examination of tissue around the fistula revealed
      squamous cell carcinoma. His quality of life was improved, but his general
      condition became worse gradually and he died of cancer.

PMID- 15732345
TI  - [Clinical study of male urethritis in Oogaki Municipal Hospital].
AB  - We studied 181 patients diagnosed with male urethritis at Oogaki Municipal
      Hospital from April 2002 to March 2004. Twenty-two out of 92 patients diagnosed
      with gonococcal urethritis (GU) and 52 out of 89 patients diagnosed with non
      gonococcal urethritis (NGU) were positive for Chlamidia trichomatis by polymerase
      chain reaction (PCR). Most patients of male urethritis were in their twenties. Of
      GU patients, 39 (67%) were infected from commercial sex workers (CSWs). Of NGU
      patients, 12 (30%) were infected from CSWs, 24 (40%) from girl friends and 4
      (10%) from their Twenty-eight (48%) out of GU patients were infected through oral
      sex. spouse. Eighty-three GU patients were treated with SPCM (2 g, one shot).
      Fifty-five patients could be evaluated for the efficacy of treatment. Elimination
      rate of Neisseria gonorrhoeae was 100% and 14 out of 18 patients with persisting
      urethritis had C. trichomatis. Eighty-two NGU patients were treated with
      minocycline, tosufloxacin, levofloxacin, gatiflixacin or clarithromycine. Sixty
      six patients could be evaluated for the efficacy of treatment. Forty-one patients
      were diagnosed with non-gonococcal chlamydial urethritis (NGCU) and 25 patients
      were diagnosed with non-gonococcal, non-chlamydial urethritis (NGNCU). The
      clinical curative rate of NGCU and NGNCU was 93% (38/41) and 80% (20/25),
      respectively.

PMID- 15732346
TI  - [Sleep disorders in the elderly].

PMID- 15732347
TI  - [Small G proteins--their roles and functions on cell-cell junction].

PMID- 15732348
TI  - [Pulmonary hypertension in elderly people].

PMID- 15732349
TI  - [Recent progress in osteoporosis research].

PMID- 15732350
TI  - [Iatrogenic neurological disorders in old people: a review].
AB  - Aged people are frequently the victims of iatrogenic diseases, especially adverse
      effects of drugs since they are affected by many age-related diseases and are
      given many drugs. Geriatric medicine in Japan has a bitter history of having
      produced many victims by adverse effects of cerebral vasodilators and cerebral
      stimulants; they included parkinsonism and depression induced by flunarizine and
      cinnarizine, and Reye-like encephalopathy induced by calcium hopantenate.
      Parkinsonism induced by sulpiride, tiapride, metoclopramide or atypical anti
      psychotics, dyskinesia induced by anti-parkinsonian drugs or anti-psychotics, and
      psychotic symptoms induced by anti-parkinsonian drugs, anti-cholinergic drugs,
      anti-depressants or histamine H2 antagonists are still very common. Wernicke
      encephalopathy caused by intravenous glucose infusion without thiamine, central
      pontine myelinolysis by too rapid correction of hyponatremia are important though
      infrequent. Iatrogenic Creutzfeldt-Jakob disease by dura grafts is a warning
      against the easy use of medical materials produced with human organs or blood.
      Iatrogenic diseases are preventable, and geriatricians have to pay attention to
      the information on adverse effects of drugs and medical materials and carefully
      observe the early signs of iatrogenic diseases.

PMID- 15732351
TI  - [Expectation of new treatments for idiopathic interstitial pneumonias].
AB  - Idiopathic pulmonary fibrosis (IPF), a chronic form of idiopathic interstitial
      pneumonia, has a poor prognosis with an average life expectancy of 3-4 years from
      the time of diagnosis. Although patients with IPF have been treated with steroids
      or immunosuppressants to control the inflammation that occurs earlier in the
      course of disease, these drugs have not improved the survival of patients with
      IPF. Recently, several clinical studies of antifibrotic drugs have been conducted
      in patients with IPF. In Japan, we demonstrated that pirfenidone prevents
      deterioration of pulmonary function and significantly decreases the incidence of
      acute exacerbation of IPF in a well-designed, placebo-controlled, double-blind,
      randomized study. We have also adopted a new system for evaluation of dynamic
      pulmonary function, which involves measuring the lowest SpO2 level during a 6
      minute walk at a constant speed and assessing the pulmonary capacity of patients
      with IPF. In a study of patients with pulmonary fibrosis associated with
      Hermansky-Pudlak syndrome in the United States, pirfenidone slowed the decrease
      in %FVC in patients with a %FVC of >60%, but had no significant effects on
      patients with a %FVC of < or =60%. Large-scale clinical studies of INF-gamma in
      patients with IPF in North America and Europe have reported decreases in the
      mortality of patients with mild IPF with a FVC of >60%, although percentages of
      patients with disease status rated as 'exacerbated', 'unchanged' and 'improved'
      after treatment did not differ between the INF-gamma and placebo groups. This
      presentation reported important future strategies for the treatment of IPF.

PMID- 15732352
TI  - [Asthma in the elderly: characteristics and management].

PMID- 15732353
TI  - [Prevention of elderly pneumonia by pneumococcal, influenza and BCG
      vaccinations].
AB  - Pneumonia is a major cause of morbidity and mortality in elderly people,
      especially in those with chronic medical conditions such as chronic heart and
      lung diseases. We prospectively examined the effect of influenza and pneumococcal
      vaccinations on the rate of hospitalization for and complications of pneumonia,
      all respiratory tract conditions and mortality in elderly bedridden patients and
      found that both febrile days and pneumonia cases decreased. Thus, these results
      show that it is valuable to vaccinate for influenza elderly people even if they
      are confined to bed. Furthermore, the tuberculin skin test is an easy method to
      check the cell-mediated immunity in the elderly people. In the tuberculin skin
      test, all Japanese over 65 years old should have positive status. A negative
      result indicates depressed cell-mediated immunity. We undertook a trial to
      vaccinate tuberculin negative elderly people with BCG vaccine and found that the
      risk of pneumonia is decreased to a similar degree to that in subjects with
      positive tuberculin test results. We conclude that vaccination might be an
      effective strategy for the prevention of pneumonia in elderly people with limited
      activities of daily living.

PMID- 15732354
TI  - [Value of FDG PET in diagnosis and management of lung cancer].

PMID- 15732355
TI  - [The meaning of the early detection of dementia].
AB  - The significance of early detection of dementia is that there is some benefit
      from almost all involved, especially, patients, their family, attending physicans
      and administration (local financial affairs), 1) Both patients and their family
      can recognize that dementia is not ageing but a disease. They can have the hope
      that early treatment of dementia can improve symptom. Moreover, their family and
      care givers can look after demented persons more easily by acquiring the
      knowledge of the official welfare system and how to cope with dementia-related
      problem behavior. These can reduce ill-treatment. 2) The improvement or
      supression of dementia symptoms, and the teaching of how to handle daily life can
      give attending physican an incentive to treat. 3) If the onset of dementia can be
      delayed for 2 years, administration can reduce expenses by 560 billion yen in all
      Japan, which would benefit the medical economy greatly.

PMID- 15732356
TI  - [The memory medical examination in Gunma].

PMID- 15732357
TI  - [Diagnostic approach to dementia in Gunma University Hospital supporting Dementia
      Gunma Network].

PMID- 15732358
TI  - [Treatment of dementia].
AB  - Drugs to treat the primary symptoms of dementia are nootropics (anti-dementia
      medicine). These can be divided into three stage historically. Drugs of brain
      metabolic improvement and blood expanssion and anti-coagulation drugs used till
      now, are the first stage. AChE inhibitor and glutamin receptor inhibitors used at
      present are second generation drugs. The cause of degenerative diseases like
      Alzheimer's disease is the accumulation of abnormal protein. So, fundamental
      medicines to prevent such accumulation are the third generation drugs. Anti
      inflammation drugs, anti-cholesterol drugs, female hormones, and nerve growth
      factors used at present are third generation grugs. In truth, only vaccine
      treatment is the third stage medicine. Adjuvant treatment is also available at
      present This approach is not based on the elimination of various causes of cell
      injury, but on increasing resistance to cell injury. These methods include
      protection of the nerve cell membrane, supply of nerve transmission material and
      improvement of brain blood flow. Non-medicinal methods of treatment and
      prevention of dementia include mental training and body movement (exercises).
      These promote supply of nutrition and oxygen to the nerve cells as a result of
      increases in brain circulation caused by the various stimuli. In addition to
      training, nutrition should also be suppled at the same time.

PMID- 15732359
TI  - [Dementia, message from caremanager--I consider it through the case].

PMID- 15732360
TI  - [A multi-center cohort study for clarifying risk factors on atherosclerosis in
      Japan (JALS)].

PMID- 15732361
TI  - [Changes in stroke incidence and mortality in a Japanese community: the Hisayama
      study].

PMID- 15732362
TI  - [Characteristics of stroke in Japan--Epidemiologic view-point by Akita stroke
      register].

PMID- 15732363
TI  - [Risk factors for stroke: epidemiological evidence from Japan].

PMID- 15732364
TI  - [Differences in the way of thinking about health and infectious diseases between
      the elderly and medical staff].
AB  - The majority of our inpatients and outpatients are senior citizens. They are in
      marked contrast to the majority of current medical workers who are far younger
      than their patients. We investigated the problems which may arise due to this age
      gap using a questionnaire asking about viewpoints on "health" and "infectious
      diseases among the elderly" Interest in general health was lower among medical
      workers than common citizens. Lifestyles which the public may consider to be good
      for health are more specific and cover a wider range than those of medical
      professionals. Medical staff thought home care is important for infectious
      diseases among the elderly. They were concerned with the appearance of resistant
      bacilli and considered that the type of treatment should vary in accordance with
      the patient's age and stamina, whereas the elderly citizens cared more strongly
      about the treatments result. Medical workers should understand that the general
      citizens have a different way of thinking about health and infectious diseases
      from their own.

PMID- 15732366
TI  - [A prospective comparison of day care and freely chosen occupational therapy for
      elderly patients with dementia].
AB  - Since the introduction of long-term care insurance, day care services have become
      popular throughout Japan and many kinds of behavioral approaches have been used.
      Although there have been many reports on the non-pharmacological effects on
      cognitive function, case control studies to evaluate the effect of day care
      services are insufficient Furthermore, no study has compared the advantages of
      different behavioral therapies for elderly subjects with loss of cognitive
      function. To clarify these issues, we compared the changes in activities of daily
      living, cognitive function and vitality/depression among 78 subjects receiving
      different day care services. Community dwelling subjects using day care (day care
      group: n = 29, 80+/-7.3 years old) showed an improvement in abnormal behavior
      (DBD scale; before 8.5+/-2.1, after 3.2+/-1.3, p<0.05). Vitality and volition
      measured by the Vitality Index were significantly preserved in the day care group
      compared with community dwelling subjects without day care services (n = 11,
      78.6+/-9.4 y.o.). Comparing the effect of three different behavioral therapies
      (physical fitness, cooking and gardening), there was no difference in changes in
      cognitive function or in other comprehensive measurements among the groups. On
      the other hand, different responses to various therapies were observed among
      subjects. To determine the advantage of various non-pharmacological therapies for
      dementia, geriatricians need to perform prospective case-control studies with a
      large number of subjects, using comprehensive geriatric assessment as the art of
      a geriatrician.

PMID- 15732365
TI  - [Behavioral, stress and immunological evaluation methods of music therapy in
      elderly patients with senile dementia].
AB  - The purpose of this study was to clarify the efficacy of behavioral, stress and
      immunological evaluation methods in music therapy (MT) with elderly patients with
      senile dementia. The MT group consisted of 8 elderly patients with dementia and
      the control group included 8 similarly matched patients. A total of 25 sessions
      of music therapy were conducted for one hour, twice each week for three months.
      The Mini-Mental State Exam (MMSE), Gottfries-Brane-Steen Scale (GBS), and
      Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) were used to
      evaluate behavioral changes. Saliva Chromogranin A (Cg A) and Immunoglobulin A
      (Ig A) were used to assess changes in stress and immunological status,
      respectively. The results of the study were as follows: 1. In GBS, the mean score
      of "different symptoms common in dementia" improved significantly after MT. 2.
      The mean Behave-AD score of "paranoid and delusional ideation" was also
      significantly improved (p<0.05) after the intervention. 3. In the 25th session,
      mean saliva Cg A was significantly decreased after MT (p<0.05). IgA was slightly
      increased prior to intervention. Our results suggest that a combination of
      behavioral, stress and immunological evaluation methods were valuable for
      assessing changes that occurred during MT for elderly patients with dementia.

PMID- 15732367
TI  - [Treatment of bedsores--combination of therapies depended the experimental design
      method].
AB  - The treatment of bedsores is a particular problem in geriatric medicine. We
      selected standard drugs that may be effective for the decubitus ulcer, and
      investigated combination therapy to develop efficient treatment The subjects were
      16 patients in whom the grade of the bedsore was evaluated as II to IV according
      to the Shea's depth classification. Treatment was performed while all patients
      were on air mats. We selected drugs and treatment methods based on the previously
      established experimental design of Taguchi. Based on this, we created and adapted
      16 different component combination treatment programs in accordance with the L16
      rectangular cross table. The following component factors were adopted: A: types
      of covering substances on the wound surface (Elase ointment, isodine sugar,
      isodine gel solcoseryl ointment); B: Isalopan powder; C: Spray of 10 ml
      physiological saline containing 500 microg of prostaglandin (concentration
      0.005%); D: daily number of treatments; and F: presence or absence of tapping. We
      serially measured the wound surface area as an index of the speed of wound
      healing, and measured the interval (day) until the area decreased to one half of
      the original size (T1/2, half life). We analyzed data on one combination
      treatment each in 16 patients. Analysis of variance of the above factors showed
      significant F values for factors A, B, D and F. The contribution rates for
      factors A, B, D and F were 37.84%, 8.47%, 14.98% and 13.81%, respectively. The
      error term (e) was 16.37%. Optimal results were seen in the groups in which
      solcoseryl ointment had been applied twice a day. In this study, prostaglandin,
      which had been anticipated to be effective, did not show any effects. The error
      term (e) suggests the presence of other healing factors including individual
      differences. Concerning this point, it well be necessary to examine a larger
      number of patients in the future. With ointment treatment alone, without using an
      air mat, it was confirmed that bedsore area reduction was extremely unstable.
      Decompression of the affected part may be a basic prevention factor and essential
      treatment of bedsores.

PMID- 15732368
TI  - [Incidence of disability in housebound elderly people living in a rural
      community].
AB  - This study aimed to explore whether being housebound is a risk factor for
      disabilities and whether low social communication increases incidence of
      disability in elderly people. A self-reported questionnaire regarding demographic
      characteristics was administered to 2,046 community-dwelling elderly people (aged
      65 and older) in October 2000, and subjects were followed up until March 2003.
      All subjects were independent in activities of daily living. In this study, being
      housebound was defined on frequency of going out, with those who left the house
      once or less per week being classified as housebound. We further classified the
      housebound into four groups: I, going out alone is difficult but social
      communication occurs; II going out alone is difficult and no social communication
      occurs; III, going out alone is possible but not undertaken often, and some
      social communication occurs; and IV, going out alone is possible but seldom
      undertaken and no social communication occurs. In this population, overall
      prevalence of being housebound was 8.5%, and about half of those who were
      housebound fit the third classification. At the end of the follow-up period,
      12.7% of subjects reported disabilities. The incidence of disability was higher
      in the housebound compared with the non-housebound. The incidence of disability
      by age was higher in housebound groups than in the non-housebound in elderly
      individuals aged under 85, but no significant differences were recognized in
      those aged over 85. In terms of housebound status, all housebound groups had
      higher levels of disability than the non-housebound. However, the groups without
      social communication (H and IV) exhibited higher incidence of disability than
      those with social communication (I and II). From the results obtained, we
      conclude that being housebound is a risk factor for disability in elderly
      individuals aged 65 to 85 years who are living independently, and that lower
      social communication also represents a risk factor for disability. This study
      appears to indicate that a frequency of going out of once or less a week is a
      valid guide for determination of housebound status.

PMID- 15732369
TI  - [The relationship between visual perception and postural control in falls of the
      elderly living in local communities].
AB  - We have examined the relationship between visual sense information, such as
      perception data and postural control, and falls among elderly people aged 65
      years or over living in Nishibiwajima-cho, Aichi Prefecture. Of 286 participants,
      204 were enrolled and analyzed, after excluding those with a visual acuity of
      less than 0.3, or the activities of daily living (ADL) index of less than 11. In
      the analysis group, 52 people (25.2%) had already had experience of falls. Two
      way analysis of variance showed that intensity of dynamic visual stimulation and
      the presence or absence of falls had a significant effect on body sway, although
      no interaction was observed. These results indicate that body sway is increased
      in those who have experience of falls, and that strong visual stimulation is
      associated with body sway. This suggests that greater dynamic visual stimulation
      is likely to increase the risk of falls.

PMID- 15732370
TI  - [Repeated changes of electrocardiogram caused by Takotsubo-type cardiomyopathy: a
      case with hypertrophic nonobstructive cardiomyopathy].
AB  - A 67-year-old woman had been examined due to abnormalities on electrocardiography
      (ECG) at a medical checkup three years previously. When a negative T-wave was
      seen in leads I, aVL, and V1 to V4, but the abnormal findings were improved at
      consultation. Echocardiography revealed apical hypertrophy and hypertrophic
      nonobstructive cardiomyopathy was diagnosed. She felt chest discomfort in
      September, 2003 and an ECG showed a negative T-wave in leads I, II, III aVL, aVF
      and V2 to V6 and an elongation of QT interval Left ventriculography revealed
      myocardial hypertrophy at the left ventricular apex and left ventriclar wall
      motion was normal. Coronary angiography did not show any significant luminal
      narrowing. I-123 metaiodobenzyl-guanitidine scintigraphy showed marked perfusion
      defects at the left ventricular apex. After five months, ECG showed an
      improvement of the QT interval and a decrease in the negative T-wave. We
      considered that the repeated changes of ECG were caused by Takotsubo-type
      cardiomyopathy.

PMID- 15732371
TI  - [A 73-year-old man with primary pulmonary hypertension].
AB  - A rare case of primary pulmonary hypertension was observed in a 73-year-old man.
      Angina pectoris was diagnosed at the age of 67 and he received several
      percutaneous coronary interventions because of refractory restenosis. He also had
      coronary artery bypass surgery at the age of 69. After 4 years, he again suffered
      from dyspnea and chest pain upon physical exertion. On admission to our hospital,
      a chest radiograph showed dilatation of bilateral pulmonary arteries. Moreover,
      echocardiography showed right ventricular dilatation and tricuspid regurgitation.
      Continuous wave Doppler imaging revealed a pressure gradient of 82.1 mmHg.
      Pulmonary capillary wedge pressure was normal, but pulmonary artery pressure was
      elevated upon cardiac catheterization. Because there was no apparent etiology of
      pulmonary hypertension, primary pulmonary hypertension was diagnosed and
      appropriate conventional therapy was started.

PMID- 15732373
TI  - [Stem cell system and regenerative medicine].

PMID- 15732372
TI  - A delayed type hypersensitivity (DTH) skin reaction to hepatitis B surface
      antigen (HBsAg) and intradermal hepatitis B vaccination.
AB  - The significance of a delayed type hypersensitivity skin reaction to hepatitis B
      surface antigen (HBsAg) (HBs-DTH) in type B viral hepatitis (VHB) and in
      intradermal hepatitis B (HB) vaccination is reviewed. HBs-DTH could be developed
      by the intradermal injection of HB vaccine in anti-HBs positive people and also
      in persons immunized with HB vaccine. Thus, HBs-DTH could serve as a useful
      marker for the acquisition of an active Th1 type immunoreactivity to HBsAg. HBs
      DTH was absent in patients with chronic VHB. In contrast, HBs-DTH developed early
      in the convalescent phase of the acute VHB, whereas the production of anti-HBs
      was significantly delayed, thus suggesting that HBs-DTH may be involved in the
      recovery mechanisms of acute VHB. Intradermal HB vaccination is useful not only
      in lowering the cost, but also in the rapid development of anti-HBs, reversing
      non-responsiveness, improving postexposure prophylaxis and in immunizing
      immunosuppressed people. A similar vaccination strategy should prove to be useful
      in prevention and control of not only other infectious diseases but also
      malignant neoplasms.

PMID- 15732374
TI  - [Evaluation of acute hepatic failure treated at the Department of Medicine III,
      Kyushu University Hospital: indications for living-donor liver transplantation].
AB  - To evaluate indications for living-donor liver transplantation (LDLT), we
      examined 25 consecutive patients with acute hepatic failure admitted to the
      Department of Medicine III, Kyushu University Hospital between November 2001 and
      July 2004. These cases were diagnosed as fluminant hepatitis (n=13), severe-type
      acute hepatitis (n=11), or late-onset hepatic failure (n=1). Nine patients (36%)
      improved with conservative treatment (conservative treatment group), and the
      other 16 patients (64%) needed LDLT (LDLT indicated group). In the LDLT indicated
      group, 11 patients received LDLT, and 4 died because of lack of LDLT donors
      (n=3), or renal failure (n=1). The LDLT survival rate was 82% (9/11); two
      patients died due to hepatic infarction and brain edema, respectively. It is very
      important to predict whether a patient with acute hepatic failure belongs to the
      conservative treatment group or the LDLT indicated group on admission. Therefore,
      we analyzed variables that could influence prognosis, including, parameters of
      hepatic function and platelet counts on admission, and relative hepatic volume
      (%), which represents the ratio of hepatic volume measured by CT relative to
      standard hepatic volume calculated with body surface area. Univariate logistic
      analysis showed that relative hepatic volume, gammaglutamyl transpeptidase (gamma
      GTP), alkaline phosphatase (ALP), and the ratio of direct bilirubin to total
      bilirubin (DB/TB) were significant predictors of survival (p < 0.05). Using these
      factors plus prothrombin time (PT) and total cholesterol, both of which were
      relatively significant predictors of survival (p < 0.2), we proposed a model for
      predicting the probability of survival by the stepwise method. Consequently, we
      proposed a model using four parameters: ALP, GGTP, PT, and relative hepatic
      volume (Volume) as shown below: p(%) = 1/(1+exp (-(-36.2375 + ALP x 0.0251 +
      gamma-GTP x 0.0102 + PT x 0.2558 + Volume 21.2158))) x 100. This model showed a
      significant correlation between prediction and consequence of survival (r2 =
      0.7388, p = 0.0003). In conclusion, LDLT is an effective treatment for acute
      hepatic failure. The results of this study suggested that our model can
      adequately predict prognosis in the early phase of acute hepatic failure.

PMID- 15732375
TI  - An introduction to the biophysics of the electrically evoked compound action
      potential.
AB  - A computational model of the electrically evoked compound action potential (ECAP)
      has been developed. In addition to being a useful research tool, it serves as an
      excellent introduction to the basic biophysics of ECAP recording techniques.
      ECAPs are modeled as a sum of single-fiber action potentials (SFAPs) in response
      to an electrical stimulus. Each SFAP is calculated from the potential induced at
      the recording site by the membrane currents arising on an axon as a spike
      propagates along it. The factors that alter SFAP and ECAP morphology and latency
      are discussed, as are the mechanisms of stimulus artefact and the advantages and
      limitations of different artefact-suppression techniques. The assumptions of the
      model are presented, as are potential ways of improving the physiologic data
      available from clinical recordings. Potential applications of this technology in
      the investigation of the biophysical mechanisms of the implanted cochlea are
      suggested.

PMID- 15732376
TI  - Evaluation of the neural response telemetry (NRT) capabilities of the nucleus
      research platform 8: initial results from the NRT trial.
AB  - The purpose of this study was to evaluate the performance of the new features of
      the Nucleus Research Platform 8 (RP8), a system developed specifically for
      research purposes The RP8 consists of a research implant, a speech processor and
      a new NRT software (NRT v4), and includes comparisons of the different artefact
      cancellation methods, NRT threshold, and recovery function measurements. The
      system has new artefact-suppression techniques and new diagnostic capabilities;
      their performance has been verified in animal experiments. In this study, NRT
      data were collected from 15 postlingually deafened adult cochlear implant
      patients intraoperatively and up to 6 months postoperatively after switch-on. The
      initial investigation in two clinics in Europe focused primarily on the enhanced
      NRT capabilities Results from the trial in two European clinics indicate that NRT
      measurements can be obtained with lower noise levels. A comparison of the
      different artefact-cancellation techniques showed that the forward-masking
      paradigm implemented in the Nucleus 3 system is still the method of choice. The
      focus of this report is on recovery function characteristics, which may give
      insight into auditory nerve fiber properties with regard to higher stimulation
      rates.

PMID- 15732377
TI  - Pre-perioperative, transtympanic electrically evoked auditory brainstem response
      in children.
AB  - The purpose of this study was to characterize the transtympanically evoked,
      perioperative electrically evoked auditory brainstem response (EABR) and define
      its relationship with preoperative hearing, age and hearing loss etiology in 59
      children (10-60 months of age) who had received cochlear implants. The results
      indicate that there was no difference between wave V latency obtained from the
      younger (10-36 months) and the older (37-60 months) children. There was a
      statistically significant difference in the preoperative pure-tone average
      between the higher-EABR threshold group (650 microA and above) and the lower-EABR
      threshold group (600 microA or less). Patients with post-meningitic deafness
      exhibited the longest EABR wave V latencies. Perioperative, transtympanic,
      promontory EABR is an effective clinical procedure which can decrease the
      likelihood of placing a cochlear implant in a non-stimulable ear, and may provide
      the clinician with a valuable tool for selecting the most appropriate ear for
      implantation.

PMID- 15732378
TI  - Characteristics of electrically evoked potentials in patients with auditory
      neuropathy/auditory dys-synchrony.
AB  - The primary goal of this study was to compare the characteristics of the post
      implant evoked potentials with preimplant evoked potentials in patients with
      auditory neuropathy (AN) or dys-synchrony. AN is typically characterized by
      sensorineural hearing loss, reduced speech perception, abnormal temporal
      processing, and unusual patterns of results with various objective audiological
      tests. In some cases, these patients may be appropriate candidates for a cochlear
      implant. In this article, we highlight evoked potential findings in two children
      diagnosed with AN who were provided with multichannel cochlear implants.
      Preoperative, interoperative and postoperative evoked potential measures show
      that the restoration of neural synchrony may occur at multiple levels of the
      auditory pathways in patients with AN when appropriate diagnostic tests, cochlear
      implantation and rehabilitation are provided.

PMID- 15732379
TI  - Programming cochlear implant stimulation levels in infants and children with a
      combination of objective measures.
AB  - We propose a method of obtaining audible and comfortable stimulation levels with
      the use of objective measures when reliable behavioral testing is not possible.
      Electrically evoked compound action potentials of the auditory nerve (ECAPs) and
      stapedius reflex (ESR) thresholds were measured in 68 children who use Nucleus
      devices, beginning at implantation in the operating room (OR) and continuing over
      the first year of implant use at three implant electrodes. Generic correction
      factors based on group data were subtracted from ECAP thresholds obtained in the
      OR. The correction factors were specified for two groups of electrodes and two
      age groups of children. Objective thresholds exceeded behavioral values in 75% of
      children and were lower than minimum ESR thresholds in 85% of children. Mean
      dynamic ranges between the two objective measures spanned 23-36 Clinical Units
      across the implanted array. Maximum levels, based on ESR thresholds measured in
      the OR, can be globally adjusted to maintain comfortable stimulation levels.

PMID- 15732380
TI  - Electrophysiologic and objective monitoring of the cochlear implant during
      surgery: implementation, audit and outcomes.
AB  - Electrophysiologic and objective measures are reviewed with respect to their
      implementation as monitoring tools for cochlear implants in the operating room
      and their value in the management of children. The current intraoperative test
      protocol in Nottingham consists of back-telemetry (BT) diagnostic testing of
      implant function, including impedance telemetry (ImpT), integrity testing (IT),
      electrical stapedius reflex response (ESR), electrical auditory brainstem
      response (EABR) and Neural Response Telemetry (NRT). Of 427 cases of implantation
      in the period 1990-2003, 303 (71%) were completely normal for all components of
      the protocol. In the remaining cases, some results were either simply anomalous,
      with no direct impact on management during surgery, and some were more
      significant, resulting in actions such as the use of the back-up device or
      repositioning of the electrode array. Normal intraoperative findings provided
      immediate reassurance to the implant team and parents of young children that the
      implant was fully functioning and that electrical stimulation was activating the
      auditory pathways These objective measures also identified potentially
      challenging cases, such as those with low levels of sensitivity to electrical
      stimulation and susceptibility to facial nerve stimulation. An audit showed that
      intraoperative measures provided valuable assistance in the initial fitting of
      the device.

PMID- 15732381
TI  - Auditory steady-state response evaluation of auditory thresholds in cochlear
      implant patients.
AB  - The aims of this work were to characterize the electrophysiologic response
      obtained by measurement of the auditory steady-state response (ASSR) in patients
      with a cochlear implant (MXM Digisonic) and to study the relationship between the
      subjective thresholds of the implantees and those estimated using electrical
      auditory steady-state response (ASSR)-based objective audiometry. Five subjects
      were examined with the use of four carrier frequencies--600, 1000, 2000 and 3500
      Hz--modulated at frequencies between 70 and 85Hz, a particular frequency of
      modulation being represented at a specific electrode (for each carrier frequency)
      as a particular pulse-width modulation frequency. The protocol consisted of
      testing output and thresholds for different overall pulse durations for several
      stimulus (pulse) intensities, rendering multiple threshold measures (in duration)
      for each subject tested. The non-linearity of response growth, as a function of
      duration, provided the basis for teasing apart physiologic response and
      electrical artefact in the suprathreshold recorded responses. Thresholds
      estimated with use of the electrical ASSR demonstrated reasonably good agreement
      with the subjective thresholds. The results obtained thus demonstrated the
      efficacy of the approach and are encouraging for further advances in cochlear
      implant applications.

PMID- 15732382
TI  - Use of the event-related P300 potential in cochlear implant subjects for the
      study of strategy-dependent speech processing.
AB  - The present overview is a compilation of the results of several event-related
      potential (ERP) studies on auditory cortical processing, performed in the Evoked
      Potential Laboratory of the University Medical Centre of Nijmegen. To study
      speech perception performance in cochlear implant (CI) subjects, ERPs were
      obtained from subjects with poor and moderate performance. The present report
      describes the relationships between speech-coding strategies, the presentation of
      speech by the CI processor, the P300 potential as a measure of speech
      discrimination, time effects in the long term and speech recognition in relation
      to ERPs.

PMID- 15732383
TI  - Low-resolution electromagnetic tomography (LORETA) in children with cochlear
      implants: a preliminary report.
AB  - The current preliminary report describes the utilization of low-resolution
      electromagnetic tomography (LORETA) in a small group of highly performing
      children using the Nucleus 22 cochlear implant (CI) and in normal-hearing (NH)
      adults. LORETA current density estimations were performed on an averaged target
      P3 component that was elicited by non-speech and speech oddball discrimination
      tasks. The results indicated that, when stimulated with tones, patients with
      right implants and NH adults (regardless of stimulated ear) showed enhanced
      activation in the right temporal lobe, whereas patients with left implants showed
      enhanced activation in the left temporal lobe. When stimulated with speech,
      patients with right implants showed bilateral activation of the temporal and
      frontal lobes, whereas patients with left implants showed only left temporal lobe
      activation. NH adults (regardless of stimulated ear) showed enhanced bilateral
      activation of the temporal and parietal lobes. The differences in activation
      patterns between patients with CI and NH subjects may be attributed to the long
      term exposure to degraded input conditions which may have resulted in
      reorganization in terms of functional specialization. The difference between
      patients with right versus left implants, however, is intriguing and requires
      further investigation.

PMID- 15732384
TI  - Functional brain imaging as an objective measure of speech perception performance
      in adult cochlear implant users.
AB  - In this study we examined the role of functional brain imaging of regional
      cerebral bloodflow (rCBF) with the use of single photon emission computed
      tomography (SPECT) for the objective measurement of brain performance in adult
      cochlear implant (CI) users during speech perception. The subjects consisted of
      nine normal-hearing and eight CI individuals who watched a 15-min videotape under
      two conditions: (1) a visual-only presentation; and (2) a left-monaural audio and
      visual presentation. Cortical activations were observed bilaterally in Brodmann
      areas 41, 42, 21, 22 and 38 for normal-hearing control subjects. Bilateral
      activations were also observed in CI individuals who demonstrated high
      performance on open-set speech recognition tasks; however, activations were
      smaller in both amplitude and extent than those observed for normal-hearing
      individuals. CI individuals with minimal open-set recognition demonstrated only
      unilateral activation of auditory cortex in the hemisphere contralateral to the
      ear of implantation. These data support SPECT as a tool for objectively
      documenting cortical activations in adult CI users.

PMID- 15732385
TI  - Foley-Sammon optimal discriminant vectors using kernel approach.
AB  - A new nonlinear feature extraction method called kernel Foley-Sammon optimal
      discriminant vectors (KFSODVs) is presented in this paper. This new method
      extends the well-known Foley-Sammon optimal discriminant vectors (FSODVs) from
      linear domain to a nonlinear domain via the kernel trick that has been used in
      support vector machine (SVM) and other commonly used kernel-based learning
      algorithms. The proposed method also provides an effective technique to solve the
      so-called small sample size (SSS) problem which exists in many classification
      problems such as face recognition. We give the derivation of KFSODV and conduct
      experiments on both simulated and real data sets to confirm that the KFSODV
      method is superior to the previous commonly used kernel-based learning algorithms
      in terms of the performance of discrimination.

PMID- 15732386
TI  - Uncertainty of data, fuzzy membership functions, and multilayer perceptrons.
AB  - Probability that a crisp logical rule applied to imprecise input data is true may
      be computed using fuzzy membership function (MF). All reasonable assumptions
      about input uncertainty distributions lead to MFs of sigmoidal shape. Convolution
      of several inputs with uniform uncertainty leads to bell-shaped Gaussian-like
      uncertainty functions. Relations between input uncertainties and fuzzy rules are
      systematically explored and several new types of MFs discovered. Multilayered
      perceptron (MLP) networks are shown to be a particular implementation of
      hierarchical sets of fuzzy threshold logic rules based on sigmoidal MFs. They are
      equivalent to crisp logical networks applied to input data with uncertainty.
      Leaving fuzziness on the input side makes the networks or the rule systems easier
      to understand. Practical applications of these ideas are presented for analysis
      of questionnaire data and gene expression data.

PMID- 15732387
TI  - Smooth function approximation using neural networks.
AB  - An algebraic approach for representing multidimensional nonlinear functions by
      feedforward neural networks is presented. In this paper, the approach is
      implemented for the approximation of smooth batch data containing the function's
      input, output, and possibly, gradient information. The training set is associated
      to the network adjustable parameters by nonlinear weight equations. The cascade
      structure of these equations reveals that they can be treated as sets of linear
      systems. Hence, the training process and the network approximation properties can
      be investigated via linear algebra. Four algorithms are developed to achieve
      exact or approximate matching of input-output and/or gradient-based training
      sets. Their application to the design of forward and feedback neurocontrollers
      shows that algebraic training is characterized by faster execution speeds and
      better generalization properties than contemporary optimization techniques.

PMID- 15732388
TI  - Mixtures-of-experts of autoregressive time series: asymptotic normality and model
      specification.
AB  - We consider a class of nonlinear models based on mixtures of local autoregressive
      time series. At any given time point, we have a certain number of linear models,
      denoted as experts, where the vector of covariates may include lags of the
      dependent variable. Additionally, we assume the existence of a latent multinomial
      variable, whose distribution depends on the same covariates as the experts, that
      determines which linear process is observed. This structure, denoted as mixture
      of-experts (ME), is considerably flexible in modeling the conditional mean
      function, as shown by Jiang and Tanner. In this paper, we present a formal
      treatment of conditions to guarantee the asymptotic normality of the maximum
      likelihood estimator (MLE), under stationarity and nonstationarity, and under
      correct model specification and model misspecification. The performance of common
      model selection criteria in selecting the number of experts is explored via Monte
      Carlo simulations. Finally, we present applications to simulated and real data
      sets, to illustrate the ability of the proposed structure to model not only the
      conditional mean, but also the whole conditional density.

PMID- 15732389
TI  - A generalized growing and pruning RBF (GGAP-RBF) neural network for function
      approximation.
AB  - This paper presents a new sequential learning algorithm for radial basis function
      (RBF) networks referred to as generalized growing and pruning algorithm for RBF
      (GGAP-RBF). The paper first introduces the concept of significance for the hidden
      neurons and then uses it in the learning algorithm to realize parsimonious
      networks. The growing and pruning strategy of GGAP-RBF is based on linking the
      required learning accuracy with the significance of the nearest or intentionally
      added new neuron. Significance of a neuron is a measure of the average
      information content of that neuron. The GGAP-RBF algorithm can be used for any
      arbitrary sampling density for training samples and is derived from a rigorous
      statistical point of view. Simulation results for bench mark problems in the
      function approximation area show that the GGAP-RBF outperforms several other
      sequential learning algorithms in terms of learning speed, network size and
      generalization performance regardless of the sampling density function of the
      training data.

PMID- 15732390
TI  - Discriminative components of data.
AB  - A simple probabilistic model is introduced to generalize classical linear
      discriminant analysis (LDA) in finding components that are informative of or
      relevant for data classes. The components maximize the predictability of the
      class distribution which is asymptotically equivalent to 1) maximizing mutual
      information with the classes, and 2) finding principal components in the so
      called learning or Fisher metrics. The Fisher metric measures only distances that
      are relevant to the classes, that is, distances that cause changes in the class
      distribution. The components have applications in data exploration,
      visualization, and dimensionality reduction. In empirical experiments, the method
      outperformed, in addition to more classical methods, a Renyi entropy-based
      alternative while having essentially equivalent computational cost.

PMID- 15732392
TI  - A flexible coefficient smooth transition time series model.
AB  - In this paper, we consider a flexible smooth transition autoregressive (STAR)
      model with multiple regimes and multiple transition variables. This formulation
      can be interpreted as a time varying linear model where the coefficients are the
      outputs of a single hidden layer feedforward neural network. This proposal has
      the major advantage of nesting several nonlinear models, such as, the self
      exciting threshold autoregressive (SETAR), the autoregressive neural network (AR
      NN), and the logistic STAR models. Furthermore, if the neural network is
      interpreted as a nonparametric universal approximation to any Borel measurable
      function, our formulation is directly comparable to the functional coefficient
      autoregressive (FAR) and the single-index coefficient regression models. A model
      building procedure is developed based on statistical inference arguments. A Monte
      Carlo experiment showed that the procedure works in small samples, and its
      performance improves, as it should, in medium size samples. Several real examples
      are also addressed.

PMID- 15732391
TI  - Geometrical interpretation and architecture selection of MLP.
AB  - A geometrical interpretation of the multilayer perceptron (MLP) is suggested in
      this paper. Some general guidelines for selecting the architecture of the MLP,
      i.e., the number of the hidden neurons and the hidden layers, are proposed based
      upon this interpretation and the controversial issue of whether four-layered MLP
      is superior to the three-layered MLP is also carefully examined.

PMID- 15732393
TI  - Incremental training of support vector machines.
AB  - We propose a new algorithm for the incremental training of support vector
      machines (SVMs) that is suitable for problems of sequentially arriving data and
      fast constraint parameter variation. Our method involves using a "warm-start"
      algorithm for the training of SVMs, which allows us to take advantage of the
      natural incremental properties of the standard active set approach to linearly
      constrained optimization problems. Incremental training involves quickly
      retraining a support vector machine after adding a small number of additional
      training vectors to the training set of an existing (trained) support vector
      machine. Similarly, the problem of fast constraint parameter variation involves
      quickly retraining an existing support vector machine using the same training set
      but different constraint parameters. In both cases, we demonstrate the
      computational superiority of incremental training over the usual batch retraining
      method.

PMID- 15732394
TI  - Incremental communication for adaptive resonance theory networks.
AB  - We have proposed earlier the incremental internode communication method to reduce
      the communication cost as well as the time of the learning process in artificial
      neural networks (ANNs). In this paper, the limited precision incremental
      communication method is applied to a class of recurrent neural networks, the
      adaptive resonance theory 2 (ART2) networks. Simulation studies are carried out
      to examine the effects of the incremental communication method on the convergence
      behavior of ART2 networks. We have found that, 7-13-b precision is sufficient to
      obtain almost the same results as those with full (32-b) precision conventional
      communication. A theoretical error analysis is also carried out to analyze the
      effects of the limited precision incremental communication. The simulation and
      analytical results show that the limited precision errors are bounded and do not
      seriously degrade the convergence of ART2 networks. Therefore, the incremental
      communication can be incorporated in parallel and special-purpose very large
      scale integration (VLSI) implementations of the ART2 networks.

PMID- 15732395
TI  - Sequential information processing using time-delay connections in ontogenic CALM
      networks.
AB  - In this paper, a variant of the categorization-and-learning-module (CALM) network
      is presented that is not only capable of categorizing sequential information with
      feedback, but can adapt its resources to the current training set. In other
      words, the modules of the network may grow or shrink depending on the complexity
      of the presented sequence-set. In the original CALM algorithm, modules did not
      have access to activations from earlier stimulus presentations. To bypass this
      limitation, we introduced time-delay connections in CALM. These connections allow
      for a delayed propagation of activation, such that information at a given time
      will be available to a module at a later timestep. In addition, modules can
      autonomously add and remove resources depending on the structure and complexity
      of the task domain. The performance of this ontogenic CALM network with time
      delay connections is demonstrated and analyzed using a sample set of overlapping
      sequences from an existing problem domain.

PMID- 15732396
TI  - Asymmetric subsethood-product fuzzy neural inference system (ASuPFuNIS).
AB  - This paper presents an asymmetric subsethood-product fuzzy neural inference
      system (ASuPFuNIS) that directly extends the SuPFuNIS model by permitting signal
      and weight fuzzy sets to be modeled by asymmetric Gaussian membership functions.
      The asymmetric subsethood-product network admits both numeric as well as
      linguistic inputs. Input nodes, which act as tunable feature fuzzifiers, fuzzify
      numeric inputs with asymmetric Gaussian fuzzy sets; and linguistic inputs are
      presented as is. The antecedent and consequent labels of standard fuzzy if-then
      rules are represented as asymmetric Gaussian fuzzy connection weights of the
      network. The model uses mutual subsethood based activation spread and a product
      aggregation operator that works in conjunction with volume defuzzification in a
      gradient descent learning framework. Despite the increase in the number of free
      parameters, the proposed model performs better than SuPFuNIS, on various
      benchmarking problems, both in terms of the performance accuracy and
      architectural economy and compares excellently with other various existing models
      with a performance better than most of them.

PMID- 15732397
TI  - Partially connected feedforward neural networks structured by input types.
AB  - This paper proposes a new method to model partially connected feedforward neural
      networks (PCFNNs) from the identified input type (IT) which refers to whether
      each input is coupled with or uncoupled from other inputs in generating output.
      The identification is done by analyzing input sensitivity changes as amplifying
      the magnitude of inputs. The sensitivity changes of the uncoupled inputs are not
      correlated with the variation on any other input, while those of the coupled
      inputs are correlated with the variation on any one of the coupled inputs.
      According to the identified ITs, a PCFNN can be structured. Each uncoupled input
      does not share the neurons in the hidden layer with other inputs in order to
      contribute to output in an independent manner, while the coupled inputs share the
      neurons with one another. After deriving the mathematical input sensitivity
      analysis for each IT, several experiments, as well as a real example (blood
      pressure (BP) estimation), are described to demonstrate how well our method
      works.

PMID- 15732398
TI  - Coordinated decentralized adaptive output feedback control of interconnected
      systems.
AB  - A decentralized adaptive output feedback control design is proposed for large
      scale interconnected systems. It is assumed that all the controllers share prior
      information about the system reference models. Based on that information, a
      linearly parameterized neural network is introduced for each subsystem to
      partially cancel the effect of the interconnections on tracking performance.
      Boundedness of error signals is shown through Lyapunov's direct method.

PMID- 15732399
TI  - Neural network-based adaptive dynamic surface control for a class of uncertain
      nonlinear systems in strict-feedback form.
AB  - The dynamic surface control (DSC) technique was developed recently by Swaroop et
      al. This technique simplified the backstepping design for the control of
      nonlinear systems in strict-feedback form by overcoming the problem of "explosion
      of complexity." It was later extended to adaptive backstepping design for
      nonlinear systems with linearly parameterized uncertainty. In this paper, by
      incorporating this design technique into a neural network based adaptive control
      design framework, we have developed a backstepping based control design for a
      class of nonlinear systems in strict-feedback form with arbitrary uncertainty.
      Our development is able to eliminate the problem of "explosion of complexity"
      inherent in the existing method. In addition, a stability analysis is given which
      shows that our control law can guarantee the uniformly ultimate boundedness of
      the solution of the closed-loop system, and make the tracking error arbitrarily
      small.

PMID- 15732400
TI  - Approach and applications of constrained ICA.
AB  - This paper presents the technique of constrained independent component analysis
      (cICA) and demonstrates two applications, less-complete ICA, and ICA with
      reference (ICA-R). The cICA is proposed as a general framework to incorporate
      additional requirements and prior information in the form of constraints into the
      ICA contrast function. The adaptive solutions using the Newton-like learning are
      proposed to solve the constrained optimization problem. The applications
      illustrate the versatility of the cICA by separating subspaces of independent
      components according to density types and extracting a set of desired sources
      when rough templates are available. The experiments using face images and
      functional MR images demonstrate the usage and efficacy of the cICA.

PMID- 15732401
TI  - Estimating optimal feature subsets using efficient estimation of high-dimensional
      mutual information.
AB  - A novel feature selection method using the concept of mutual information (MI) is
      proposed in this paper. In all MI based feature selection methods, effective and
      efficient estimation of high-dimensional MI is crucial. In this paper, a pruned
      Parzen window estimator and the quadratic mutual information (QMI) are combined
      to address this problem. The results show that the proposed approach can estimate
      the MI in an effective and efficient way. With this contribution, a novel feature
      selection method is developed to identify the salient features one by one. Also,
      the appropriate feature subsets for classification can be reliably estimated. The
      proposed methodology is thoroughly tested in four different classification
      applications in which the number of features ranged from less than 10 to over
      15,000. The presented results are very promising and corroborate the contribution
      of the proposed feature selection methodology.

PMID- 15732402
TI  - Data classification with radial basis function networks based on a novel kernel
      density estimation algorithm.
AB  - This paper presents a novel learning algorithm for efficient construction of the
      radial basis function (RBF) networks that can deliver the same level of accuracy
      as the support vector machines (SVMs) in data classification applications. The
      proposed learning algorithm works by constructing one RBF subnetwork to
      approximate the probability density function of each class of objects in the
      training data set. With respect to algorithm design, the main distinction of the
      proposed learning algorithm is the novel kernel density estimation algorithm that
      features an average time complexity of O(n log n), where n is the number of
      samples in the training data set. One important advantage of the proposed
      learning algorithm, in comparison with the SVM, is that the proposed learning
      algorithm generally takes far less time to construct a data classifier with an
      optimized parameter setting. This feature is of significance for many
      contemporary applications, in particular, for those applications in which new
      objects are continuously added into an already large database. Another desirable
      feature of the proposed learning algorithm is that the RBF networks constructed
      are capable of carrying out data classification with more than two classes of
      objects in one single run. In other words, unlike with the SVM, there is no need
      to resort to mechanisms such as one-against-one or one-against-all for handling
      datasets with more than two classes of objects. The comparison with SVM is of
      particular interest, because it has been shown in a number of recent studies that
      SVM generally are able to deliver higher classification accuracy than the other
      existing data classification algorithms. As the proposed learning algorithm is
      instance-based, the data reduction issue is also addressed in this paper. One
      interesting observation in this regard is that, for all three data sets used in
      data reduction experiments, the number of training samples remaining after a
      naive data reduction mechanism is applied is quite close to the number of support
      vectors identified by the SVM software. This paper also compares the performance
      of the RBF networks constructed with the proposed learning algorithm and those
      constructed with a conventional cluster-based learning algorithm. The most
      interesting observation learned is that, with respect to data classification, the
      distributions of training samples near the boundaries between different classes
      of objects carry more crucial information than the distributions of samples in
      the inner parts of the clusters.

PMID- 15732403
TI  - New adaptive color quantization method based on self-organizing maps.
AB  - Color quantization (CQ) is an image processing task popularly used to convert
      true color images to palletized images for limited color display devices. To
      minimize the contouring artifacts introduced by the reduction of colors, a new
      competitive learning (CL) based scheme called the frequency sensitive self
      organizing maps (FS-SOMs) is proposed to optimize the color palette design for
      CQ. FS-SOM harmonically blends the neighborhood adaptation of the well-known self
      organizing maps (SOMs) with the neuron dependent frequency sensitive learning
      model, the global butterfly permutation sequence for input randomization, and the
      reinitialization of dead neurons to harness effective utilization of neurons. The
      net effect is an improvement in adaptation, a well-ordered color palette, and the
      alleviation of underutilization problem, which is the main cause of visually
      perceivable artifacts of CQ. Extensive simulations have been performed to analyze
      and compare the learning behavior and performance of FS-SOM against other vector
      quantization (VQ) algorithms. The results show that the proposed FS-SOM
      outperforms classical CL, Linde, Buzo, and Gray (LBG), and SOM algorithms. More
      importantly, FS-SOM achieves its superiority in reconstruction quality and
      topological ordering with a much greater robustness against variations in network
      parameters than the current art SOM algorithm for CQ. A most significant bit
      (MSB) biased encoding scheme is also introduced to reduce the number of parallel
      processing units. By mapping the pixel values as sign-magnitude numbers and
      biasing the magnitudes according to their sign bits, eight lattice points in the
      color space are condensed into one common point density function. Consequently,
      the same processing element can be used to map several color clusters and the
      entire FS-SOM network can be substantially scaled down without severely
      scarifying the quality of the displayed image. The drawback of this encoding
      scheme is the additional storage overhead, which can be cut down by leveraging on
      existing encoder in an overall lossy compression scheme.

PMID- 15732404
TI  - Precision constrained stochastic resonance in a feedforward neural network.
AB  - Stochastic resonance (SR) is a phenomenon in which the response of a nonlinear
      system to a subthreshold information-bearing signal is optimized by the presence
      of noise. By considering a nonlinear system (network of leaky integrate-and-fire
      (LIF) neurons) that captures the functional dynamics of neuronal firing, we
      demonstrate that sensory neurons could, in principle harness SR to optimize the
      detection and transmission of weak stimuli. We have previously characterized this
      effect by use of signal-to-noise ratio (SNR). Here in addition to SNR, we apply
      an entropy-based measure (Fisher information) and compare the two measures of
      quantifying SR. We also discuss the performance of these two SR measures in a
      full precision floating point model simulated in Java and in a precision limited
      integer model simulated on a field programmable gate array (FPGA). We report in
      this study that stochastic resonance which is mainly associated with floating
      point implementations is possible in both a single LIF neuron and a network of
      LIF neurons implemented on lower resolution integer based digital hardware. We
      also report that such a network can improve the SNR and Fisher information of the
      output over a single LIF neuron.

PMID- 15732405
TI  - Bio-basis function neural network for prediction of protease cleavage sites in
      proteins.
AB  - The prediction of protease cleavage sites in proteins is critical to effective
      drug design. One of the important issues in constructing an accurate and
      efficient predictor is how to present nonnumerical amino acids to a model
      effectively. As this issue has not yet been paid full attention and is closely
      related to model efficiency and accuracy, we present a novel neural learning
      algorithm aimed at improving the prediction accuracy and reducing the time
      involved in training. The algorithm is developed based on the conventional radial
      basis function neural networks (RBFNNs) and is referred to as a bio-basis
      function neural network (BBFNN). The basic principle is to replace the radial
      basis function used in RBFNNs by a novel bio-basis function. Each bio-basis is a
      feature dimension in a numerical feature space, to which a nonnumerical sequence
      space is mapped for analysis. The bio-basis function is designed using an amino
      acid mutation matrix verified in biology. Thus, the biological content in protein
      sequences can be maximally utilized for accurate modeling. Mutual information
      (MI) is used to select the most informative bio-bases and an ensemble method is
      used to enhance a decision-making process, hence, improving the prediction
      accuracy further. The algorithm has been successfully verified in two case
      studies, namely the prediction of Human Immunodeficiency Virus (HIV) protease
      cleavage sites and trypsin cleavage sites in proteins.

PMID- 15732406
TI  - Gabor wavelet associative memory for face recognition.
AB  - This letter describes a high-performance face recognition system by combining two
      recently proposed neural network models, namely Gabor wavelet network (GWN) and
      kernel associative memory (KAM), into a unified structure called Gabor wavelet
      associative memory (GWAM). GWAM has superior representation capability inherited
      from GWN and consequently demonstrates a much better recognition performance than
      KAM. Extensive experiments have been conducted to evaluate a GWAM-based
      recognition scheme using three popular face databases, i.e., FERET database,
      Olivetti-Oracle Research Lab (ORL) database and AR face database. The
      experimental results consistently show our scheme's superiority and demonstrate
      its very high-performance comparing favorably to some recent face recognition
      methods, achieving 99.3% and 100% accuracy, respectively, on the former two
      databases, exhibiting very robust performance on the last database against
      varying illumination conditions.

PMID- 15732407
TI  - State estimation for delayed neural networks.
AB  - In this letter, the state estimation problem is studied for neural networks with
      time-varying delays. The interconnection matrix and the activation functions are
      assumed to be norm-bounded. The problem addressed is to estimate the neuron
      states, through available output measurements, such that for all admissible time
      delays, the dynamics of the estimation error is globally exponentially stable. An
      effective linear matrix inequality approach is developed to solve the neuron
      state estimation problem. In particular, we derive the conditions for the
      existence of the desired estimators for the delayed neural networks. We also
      parameterize the explicit expression of the set of desired estimators in terms of
      linear matrix inequalities (LMIs). Finally, it is shown that the main results can
      be easily extended to cope with the traditional stability analysis problem for
      delayed neural networks. Numerical examples are included to illustrate the
      applicability of the proposed design method.

PMID- 15732409
TI  - The changing world of military health care.

PMID- 15732410
TI  - Hypertonic saline.
AB  - The optimal fluid for the resuscitation of critically ill and injured patients
      remains the subject of considerable controversy. Hypertonic crystalloid solutions
      such as hypertonic saline provide rapid volume expansion, have an acceptable
      safety profile, and are easy to store and transport. Recent meta-analyses suggest
      a trend toward increased survival in patients given hypertonic saline, and it has
      been suggested that they may have particular benefit in certain groups of
      patients such as hypovolaemic head injury patients. This short review examines
      the physiological and experimental evidence supporting the use of hypertonic
      saline in fluid resuscitation.

PMID- 15732411
TI  - Training injuries--how clinicians can help commanders avoid them.
AB  - The aim of this paper is to reflect on the proceedings of three training injuries
      symposia run by the British Army's training organization from 2001 to 2003. The
      essence of the presentations are reproduced, highlighting the role of medical
      staff in advising commanders on how injuries might be prevented. The importance
      of placing the emphasis on prevention rather than rehabilitation as a means of
      reducing the impact of training injuries is first examined. Pre-employment
      medical selection standards, the design of training courses, nutrition, smoking,
      training injuries among women, heat injury and the psycho-social environment are
      then all reviewed. Finally, the outcome of workshop discussion groups are
      presented as practical guidance for medical officers and other clinicians,
      advising commanders on how training injuries amongst their personnel might be
      minimised.

PMID- 15732412
TI  - EX SAIF SEREEA II--the field hospital clinical report.
AB  - This paper places on record the clinical activity of the hospital facilities run
      by 22 Field Hospital on Exercise SAIF SEREEA II in Oman from August to November
      2001. There were 1322 episodes of illness resulting in a hospital admission. The
      mean rate of admission was 1.96 patients per thousand per day (SD 13.62). The
      main causes of admission were gastrointestinal illness, conditions related to the
      heat and injuries. The reporting of health service utilisation data is an
      important duty of medical personnel during overseas deployments in order to add
      to the dataset available for the estimation of medical workload for future
      operations.

PMID- 15732413
TI  - Vulnerable groups of displaced populations.

PMID- 15732414
TI  - The incidence and occupational outcome of overuse anterior knee pain during army
      recruit training.
AB  - OBJECTIVES: To determine the incidence and occupational outcome of overuse
      anterior knee pain (AKP) in Army recruits undergoing basic training. METHODS: A
      prospective cohort study of 1008 Army recruits. Recruits underwent the 12-week
      phase 1 training program. Cases of AKP were captured through self-presentation of
      pain at a primary care medical centre. All recruits medical records were reviewed
      on leaving training and any other lower limb injuries were recorded for
      comparison with the AKP group. Training outcomes in terms of medical discharges
      (MD) and discharges as of right (DAOR) i.e, voluntary discharge, were recorded
      along with training days lost (TDL) and whether a recruit had been held back in
      training (BS). RESULTS: 8.75% (95% CI: 6.93-10.57) of recruits reported to the
      medical centre with AKP. Of these more than half were referred to see a GP and
      the majority were from patients with no previous history of AKP (91%, 95% CI:
      85.2-97.5). The median TDL per AKP case was 3 days (IQR: 3-5 days). The AKP group
      had a significantly higher (p < 0.01) MD rate (12.5%) than the lower limb injury
      group (3.3%; 95% CI diff: 1.1-17.2%) and the baseline rate of all other recruits
      (2.5%; 95% CI diff: 2.3-17.7%). The majority of AKP cases occurred by week 4
      (median) of training (IQR: 2.2-64). CONCLUSIONS: There was a high incidence of
      AKP, and while the short term prognosis appears relatively good in the majority
      of cases as reflected in the median TDL, a large minority were medically
      discharged and held back in training. Further work should examine methods of
      reducing the disease burden of AKP in the Army, addressing areas such as
      aetiology, prevention and treatment.

PMID- 15732415
TI  - Paediatric casualties during OP TELIC.
AB  - AIM: To audit all paediatric attendances to a British Army Field Hospital during
      warfighting. POPULATION: All patients <16-years-old who presented to 34 Field
      Hospital Accident & Emergency (A&E) Department during warfighting phase of
      OPTELIC (27 Mar 03 to 01 May 03). METHOD: A retrospective analysis of A&E
      attendance register, A&E clinical records, and A&E trainees' logbooks from the
      department of 34 Field Hospital. RESULTS: Seventy eight children were treated,
      mean age 7.9 years. 65.4% were male and 34.6% female. Children accounted for 2.9%
      of all patients (total attendances 2720) and 32.9% of non-coalition patients (non
      coalition attendances 237). 44 (56%) children had burns as the principal injury;
      7 (9%) had shrapnel injuries, 5 (6%) had blunt trauma from a road traffic
      accident. Only one child had GSW. 17% of attendances were related to 'medical'
      complaints rather than trauma. 78% of children required transfer to a specialist
      facility. CONCLUSIONS: Recognition of the potential for paediatric casualties is
      required to facilitate appropriate planning, training and equipping of medical
      units deployed on future operations.

PMID- 15732416
TI  - Self-assessment questions in the management of ophthalmic emergencies.

PMID- 15732417
TI  - General medicine.

PMID- 15732418
TI  - The Diploma in Mountain Medicine.

PMID- 15732419
TI  - Captain Oswald Hope Robertson.

PMID- 15732420
TI  - The first army medical corps?

PMID- 15732421
TI  - Hypovolemic shock: an overview.
AB  - Resuscitation of major trauma victims suffering from shock remains a challenge
      for trauma systems and trauma centers. Rapid identification, and ensuring
      correct, aggressive treatment, are necessary for patient survival. This article
      discusses shock encountered in trauma victims: hypovolemic, cardiogenic,
      obstructive, and distributive shock. Emphasis is placed on hypovolemic shock and
      its sequelae. The critical care nurse plays an important role as part of the team
      involved in the resuscitation and ongoing care of these patients. Understanding
      the underlying pathophysiology, recognizing signs and symptoms, and being
      prepared to effectively respond will further enable the nurse to contribute to
      positive patient outcomes.

PMID- 15732422
TI  - Thoracic trauma: the deadly dozen.
AB  - Deadly Dozen ... Lethal Six ... Hidden Six ... Major thoracic injuries are known
      as the Deadly Dozen. The Lethal Six (airway obstruction, tension pneumothorax,
      cardiac tamponade, open pneumothorax, massive hemothorax, and flail chest) are
      immediate, life-threatening injuries that require evaluation and treatment during
      primary survey. The Hidden Six (thoracic aortic disruption, tracheobronchial
      disruption, myocardial contusion, traumatic diaphragmatic tear, esophageal
      disruption, and pulmonary contusion) are potentially life-threatening injuries
      that should be detected during secondary survey. Each of these may present as
      immediately life-threatening or potentially life-threatening events. This article
      provides an overview of these 12 injuries and appropriate management for each.
      Case studies are included.

PMID- 15732423
TI  - Penetrating and blunt abdominal trauma.
AB  - This article is an overview of abdominal trauma relating to both penetrating and
      blunt mechanisms of injury. The incidence of abdominal injuries is discussed.
      Illustrated through case studies are interventions and treatment applicable to
      nursing practice. General principles of abdominal assessment are included.
      Anatomy and physiology of the different organ systems, as well as complications,
      is briefly overviewed. Differences between solid and hollow organs are reviewed.
      Pearls and pitfalls that impact nursing practice are presented for specific
      injuries.

PMID- 15732424
TI  - Orthopedic trauma: critical care nursing issues.
AB  - Orthopedic trauma is frequently encountered by critical care nurses as trauma
      team members providing care to the severely injured. Through actual case
      examples, the role of the critical care nurse and orthopedic trauma management is
      reviewed. Focus is on unstable pelvic fractures, extremity fractures, compartment
      syndrome, rhabdomyolysis, mangled extremities, gunshot-wound fractures, and
      damage-control orthopedics.

PMID- 15732425
TI  - Prevention and treatment of deep vein thrombosis and pulmonary embolism in
      critically ill patients.
AB  - Deep vein thrombosis and pulmonary embolism remain common problems in the
      intensive care unit, with limb- and life-threatening complications that are
      potentially preventable. The intensive care unit clinician is called on to be
      vigilant with diagnosis and facile with prevention and treatment of
      thromboembolic disease (venous thromboembolism). This article reviews background,
      current options, and recommendations regarding the occurrence of deep vein
      thrombosis and pulmonary embolism in the intensive care unit population.

PMID- 15732426
TI  - Necrotizing fasciitis: review of pathophysiology, diagnosis, and treatment.
AB  - Although the number of patients presenting with necrotizing fasciitis remains
      small, the cases seen by practitioners become legendary. The purpose of this
      article is to demystify NF through a review of the pathophysiology and the
      clinical presentation of NE Recommended diagnostic and treatment modalities are
      also discussed. Future research is recommended in the area of advanced therapies,
      such as hyperbaric oxygenation and the utilization of burn centers. Without
      further advances, the practitioner must continue to be vigilant in completing
      rapid diagnosis and treatment so as to decrease morbidity and mortality in this
      patient population.

PMID- 15732428
TI  - Treatment options in the management of uncomplicated skin and skin structure
      infections.

PMID- 15732429
TI  - The lessons of Vioxx.

PMID- 15732427
TI  - Bioethical issues concerning death: death, dying, and end-of-life rights.
AB  - Ethical issues about death, dying, and a person's right to make end-of-life
      decisions have become one of the most legally complex and culturally sensitive
      areas to emerge in our time. Sensitive issues associated with a terminally ill
      individual's right to make end-of-life decisions and the disposition of those who
      are unable to make such decisions for themselves will keep healthcare
      professionals, medical ethicists, counselors, families, lawyers, judges, and
      legislators busy for years to come. Americans find it difficult to deal with end
      of-life issues and would rather focus on what more can be done to save a life.

PMID- 15732430
TI  - What is your diagnosis? Granular cell tumor.

PMID- 15732431
TI  - Skin care of the healthy newborn.
AB  - Routine care of a newborn may be an intimidating task for new parents. This
      routine care includes tending to the skin of the infant. Maintaining a healthy,
      intact cutaneous barrier is important psychologically for the parent and
      medically for the child. Clinicians should be able to offer guidance concerning
      the basics of skin care, to dispel any misconceptions concerning baby products,
      and to optimize cutaneous integrity for the comfort and well being of the infant.

PMID- 15732432
TI  - A case of Kaposi varicelliform eruption in Darier-White disease.
AB  - Darier-White disease (DWD), otherwise known as keratosis follicularis, is a rare
      disorder of keratinization of the epidermis, mucous membranes, and nails. It is
      autosomal dominant in transmission. Patients with DWD are prone to frequent
      superinfection including the rare complication of Kaposi varicelliform eruption.
      It is postulated that a defect in cell-mediated immunity may contribute to this
      predisposition.

PMID- 15732433
TI  - Erythromelalgia misdiagnosed as cellulitis.
AB  - This case report examines the presentation of a patient with erythromelalgia that
      was misdiagnosed as cellulitis on several prior occasions. The presentation of
      bilateral acral edema and erythema, especially in the setting of
      myeloproliferative and/or connective tissue diseases, should alert the physician
      to the possibility of alternate diagnoses, including erythromelalgia. Treatments
      target symptom alleviation, as well as diagnosis and treatment of causative
      factors.

PMID- 15732434
TI  - Cutaneous and pulmonary sarcoidosis in association with tattoos.
AB  - Sarcoidosis encompasses a heterogeneous spectrum of clinical presentations,
      including sarcoidosis in association with tattoos. We report the development of
      cutaneous and pulmonary sarcoidosis in a patient with long-standing eyebrow
      tattoos whose cutaneous sarcoidosis almost completely resolved when treated with
      tacrolimus 0.1% ointment. A 70-year-old woman with a 3-year history of an
      erythematous eruption circumscribing her eyebrow tattoos presented with a
      chronic, nonproductive cough of 8 months' duration. Skin biopsy results
      demonstrated naked tubercles consistent with sarcoidosis. Results of radiographs
      and a computed tomography scan of the chest revealed multiple pulmonary nodules
      with mediastinal and hilar adenopathy. The results of transbronchial biopsy were
      consistent with the diagnosis of pulmonary sarcoidosis. Initial treatment with
      oral prednisone only improved the pulmonary sarcoidosis. The cutaneous
      sarcoidosis almost completely resolved after the addition of tacrolimus 0.1%
      ointment.

PMID- 15732435
TI  - Leuprolide acetate-induced dermatitis herpetiformis.
AB  - Dermatitis herpetiformis (DH) is a chronic, pruritic, papulovesicular dermatosis
      on extensor surfaces that is characterized by a neutrophilic infiltrate and
      granular immunoglobulin A deposition at the dermal papillae. Although the
      presence of immunoglobulin A in the skin and the severity of DH are known to be
      associated with gluten intake, few drugs have been implicated in the induction of
      DH. We report a case of DH triggered by intramuscular injections of leuprolide
      acetate, a gonadotropin-releasing hormone analog, in a patient with a history of
      prostate cancer.

PMID- 15732436
TI  - Leukemia cutis at the site of trauma in a patient with Burkitt leukemia.
AB  - Leukemia cutis is an infrequent finding in patients with acute lymphocytic
      leukemia (ALL). We present a patient with Burkitt ALL (L3ALL) who developed
      leukemia cutis at the site of trauma.

PMID- 15732437
TI  - Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%: a safe and
      efficacious 12-month treatment for melasma.
AB  - This article describes a long-term, multicenter, open-label, 12-month study of
      once-daily fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05% (Tri
      Luma Cream, hereinafter called TC [triple combination]) application in the
      treatment of melasma. A total of 228 patients with facial melasma were enrolled
      and treated; 173 patients (76%) completed the study. Most patients had 1 to 2
      courses of treatment lasting approximately 6 months in total. TC cream showed a
      favorable safety profile. only 3 patients (1%) withdrew from the study due to
      treatment-related adverse events (AEs). A total of 129 patients (57%) experienced
      at least one treatment-related AE. Most AEs were expected application-site
      reactions that were mild and transient in nature and did not require remedial
      therapy. There were no cases of skin atrophy or skin thinning and only 6 cases of
      telangiectasia (5 mild and 1 moderate), most of which had improved by the end of
      the study. Results of the efficacy assessments were positive, with both the
      patient and the physician assessing melasma to be either completely or nearly
      cleared by the end of the study in more than 90% of cases. In this study, a once
      daily application of TC cream over an extended period of 12 months showed no
      notable safety concerns and offered an effective treatment for melasma.

PMID- 15732438
TI  - Perspectives. In medicine & health perspectives this week... 'A' for effort on
      final rule, but no guarantee part D will succeed.

PMID- 15732440
TI  - Ipecac syrup-induced emesis...no evidence of benefit.

PMID- 15732439
TI  - Guideline on the use of ipecac syrup in the out-of-hospital management of
      ingested poisons.
AB  - The use of gastric emptying techniques, including ipecac-induced emesis, in the
      management of poisoned patients has declined significantly in recent years.
      Historically, poison centers used ipecac syrup in two ways. Ipecac syrup was
      administered to patients prior to referral to the emergency department in
      attempts to start the gastric emptying process as early as possible.
      Additionally, poison centers used ipecac syrup in attempts to keep patients from
      requiring referral to medical facilities. In these situations, ipecac syrup was
      administered in the home and poison center staff performed follow-up telephone
      calls to gauge progress and outcome. Studies to determine the effectiveness of
      ipecac syrup demonstrate that it induces vomiting in a high percentage of people
      to whom it is administered and that it decreases the gastrointestinal absorption
      of ingested substances in a time-dependent fashion. However, the effectiveness of
      ipecac syrup in affecting patient outcome has not been studied in adequate
      clinical trials. Its effectiveness in preventing drug absorption has only been
      documented for a limited number of substances and is substantially reduced if it
      is given more than 30-90 minutes following ingestion of the toxic material. There
      are potentially significant contraindications, adverse effects and related
      problems associated with the use of ipecac syrup. It is the consensus of the
      panel that the circumstances in which ipecac-induced emesis is the appropriate or
      desired method of gastric decontamination are rare. The panel concluded that the
      use of ipecac syrup might have an acceptable benefit-to-risk ratio in rare
      situations in which: there is no contraindication to the use of ipecac syrup; and
      there is substantial risk of serious toxicity to the victim; and there is no
      alternative therapy available or effective to decrease gastrointestinal
      absorption (e.g., activated charcoal); and there will be a delay of greater than
      1 hour before the patient will arrive at an emergency medical facility and ipecac
      syrup can be administered within 30-90 minutes of the ingestion; and ipecac syrup
      administration will not adversely affect more definitive treatment that might be
      provided at a hospital. In such circumstances, the administration of ipecac syrup
      should occur only in response to a specific recommendation from a poison center,
      emergency department physician, or other qualified medical personnel. The panel
      decided not to address the issue of whether ipecac should remain a
      nonprescription, over-the-counter product. The panel does not support the routine
      stocking of ipecac in all households with young children but was unable to reach
      consensus on which households with young children might benefit from stocking
      ipecac. Instead, the panel concluded that individual practitioners and poison
      control centers are best able to determine the particular patient population,
      geographic and other variables that might influence the decision to recommend
      having ipecac on hand.

PMID- 15732441
TI  - Parallax view.

PMID- 15732442
TI  - Outbreak of food-borne illness associated with plant material containing
      raphides.
AB  - BACKGROUND: Many botanicals, particularly ornamental house-plants, contain
      crystals of calcium oxalate called raphides. Raphides have known toxic effects
      when chewed, including painful edema, vesicle formation, and dysphagia. We report
      a food-borne illness outbreak associated with ingestion of raphides. METHODS: On
      February 24, 2003, the Chicago Department of Public Health was notified of
      multiple cases of oral burning and facial edema associated with lunch in an
      office cafeteria on February 21. The investigation included a case-control study,
      interviews with kitchen staff, an environmental inspection, and laboratory
      analysis of leftover foods. RESULTS: Ten cases were identified, including one
      admitted to the Intensive Care Unit for potential airway obstruction secondary to
      severe edema, and another seen by Emergency Department staff for oral edema and
      pain. Ten of 10 case-patients reported oral stinging and burning, and 8 of 10
      reported dysphagia. Four of 10 case-patients continued to have symptoms 2 weeks
      later. Food from the cafeteria's international buffet was consumed by 10 of 10
      case-patients and by 1 of 22 control subjects (odds ratio=undefined); each of the
      10 case-patients reported consumption of a Chinese vegetable entree from the
      international buffet and had no other foods in common. Plant material from the
      Chinese vegetable entree contained raphides. CONCLUSION: This outbreak was
      associated with consumption of raphides resembling those from common botanicals.
      Clinicians and public health practitioners should be aware of raphide-containing
      plants as a potential cause of food-borne illness.

PMID- 15732443
TI  - Seizures reported in association with use of dietary supplements.
AB  - BACKGROUND: Seizures in persons using dietary supplements (DS) have been reported
      through the Food and Drug Administration's (FDA) MedWatch system, but not
      formally reviewed. METHODS: Sixty-five cases of DS-associated seizures reported
      to MedWatch from 1993 to 1999 were obtained through the Freedom of Information
      Act and independently evaluated by three reviewers for probability of causation
      based on temporal relationship, biological plausibility, and underlying risk
      factors. Our aims in this review were 1) to assess the probability of causation
      in each case; 2) to characterize the patterns of use and types of supplements
      involved in cases of seizures; and 3) to identify trends that may explain
      potential risks factors for dietary supplement-related seizures. RESULTS: Twenty
      seizures were judged as probably related, 13 possibly related, and 10 as
      unrelated to DS use. Five cases were not seizures, and 17 cases contained
      insufficient information. In the 20 probably related cases, 19 involved ephedra,
      14 involved herbal caffeine, and in one case, the supplement contained no herbal
      constituents but an array of elemental salts. Ephedra was also associated with 7
      of the 13 possibly related cases, and caffeine was contained in 5 of these
      supplement products. Creatine, St. John's wort, and ginkgo biloba were other DS
      implicated in possibly related seizure events. Seizures were associated with
      hypoglycemia in 3 cases, and secondary to stroke in 2 cases and cardiac arrest in
      2 cases. Weight loss (45%) and athletic performance enhancement (30%) were the
      most often cited reasons for supplement use. In most cases, DS use was within
      manufacturers' guidelines. CONCLUSION: Ephedra was implicated in 27 of 33 DS
      associated seizures reported to the FDA over a 7-year period, further
      underscoring that significant health risks are associated with use of this herbal
      product.

PMID- 15732444
TI  - Experiences of a poison center network with renal insufficiency in acetaminophen
      overdose: an analysis of 17 cases.
AB  - OBJECTIVE: Renal insufficiency is less common than liver failure in acetaminophen
      overdose but renal tubular damage occurs even in the absence of hepatotoxicity.
      Data published on this topic are rare consisting mostly of case reports or
      reports in a small number of patients. Presently, a larger number of patients
      with renal insufficiency associated with acetaminophen overdose should be
      analyzed using a multicenter approach. STUDY DESIGN: Retrospective analysis of
      patients with acetaminophen-related nephrotoxicity reported to a poison center
      network from 1995 to 2003. Renal insufficiency was defined as elevated serum
      creatinine of more than double of the normal range (>2.4 mg/dL [212 micromol/L]).
      Patients were classified into 4 groups (A: creatinine 2.4-5.0 mg/dL, B:
      creatinine>5.0 mg/dL requiring no dialysis, C: creatinine>5.0 mg/dL requiring
      dialysis, D: creatinine>5.0 mg/dL with fatal outcome). RESULTS: Seventeen
      patients were included (8 female, 9 male, average age 31.7 +/- 21.1 yrs) with 6
      patients in group A (B: 7, C: 2, D: 2). In 5 patients renal insufficiency
      occurred without elevation of liver enzymes. Regarding possible risk factors 5
      patients concomitantly ingested nephrotoxic substances, 4 presented with
      dehydration due to vomiting, 4 with chronic excessive dosing (overdose) of
      acetaminophen, 3 showed pre-existing renal insufficiency, 2 pre-existing liver
      disease and 2 died with multiple organ failure. CONCLUSIONS: Renal insufficiency
      in acetaminophen overdose mostly resolved without dialysis and occurred isolated
      without hepatotoxicity in less than one-third of the investigated patients.
      Conditions which might play a role as influencing factors for renal complications
      included concomitant ingestion of nephrotoxic drugs, dehydration, chronic
      excessive dosing (overdose) of acetaminophen, pre-existing renal or liver disease
      and multiple organ failure. Renal function should be monitored in acetaminophen
      overdose particularly in patients showing the latter comorbidity.

PMID- 15732445
TI  - Carisoprodol intoxications and serotonergic features.
AB  - The symptoms and signs of carisoprodol intoxications do not resemble those caused
      by its metabolite meprobamate. Meprobamate most probably produces its effects
      through the GABAergic neurotransmitter system. The signs and symptoms of
      carisoprodol intoxications, however, are not easily explained by interaction with
      this neurotransmitter system. In the present study, four cases of carisoprodol
      intoxications are presented with emphasis on the presence of serotonergic signs
      and symptoms. All four cases fulfilled three different sets of criteria for the
      diagnosis of serotonin syndrome. These findings could indicate that an increased
      serotonin level in the central nervous system could explain some of the symptoms
      and signs of carisoprodol intoxications. This may have implications for the
      clinical evaluation and treatment of such intoxications. Since few laboratories
      routinely screen for carisoprodol it is important to keep this drug in mind when
      encountering intoxications displaying serotonergic symptoms.

PMID- 15732446
TI  - Juniper tar poisoning.
AB  - Juniper tar (cade oil) is distilled from the branches and wood of Juniperus
      oxycedrus. It contains etheric oils, triterpene and phenols, and is used for many
      purposes in folk medicine. A case is reported of a previously healthy man who
      ingested a spoonful of home-made extract of Juniperus oxycedrus. The poisoning
      caused fever, severe hypotension, renal failure, hepatotoxicity, and severe
      cutaneous burns on the face. After supportive and symptomatic treatment, the
      patient improved and was discharged in a good condition on the eleventh day.

PMID- 15732447
TI  - Digoxin toxicity: pediatric survival after asystolic arrest.
AB  - We report the first case of a child with known cardiac disease who presented in
      full cardiac arrest secondary to digoxin poisoning and was successfully
      resuscitated. A 12-week-old female presented 1-week status post surgical repair
      of a congenital heart anomaly in asystolic cardiac arrest. The patient was
      successfully resuscitated with standard Advanced Pediatric Life Support. A toxic
      digoxin level returned, Digoxin-specific antibody fragments (Digibind, Fab) were
      administered, and all signs and symptoms of toxicity resolved. The patient was
      discharged 6 days after presentation with full neurological recovery.

PMID- 15732448
TI  - Sulfur mustard: cutaneous exposure.

PMID- 15732449
TI  - Benign clinical course following atomoxetine overdose.

PMID- 15732450
TI  - Gastrointestinal decontamination triangle.

PMID- 15732451
TI  - High infection rates of the tick Hyalomma anatolicum anatolicum with Trypanosoma
      theileri.
AB  - A crossbred calf (3 months old) obtained from a farm where regular control of
      ticks was practised and found to be free of blood parasites was inoculated with
      20 ml pooled blood collected from four field cattle which had very low
      Trypanosoma theileri parasitaemias (one parasite per 70 microl blood as
      determined by the haematocrit centrifugation technique). Trypanosoma theileri was
      present in the blood 6 days after injection and a peak parasitaemia of 42
      parasites per 70 microl blood was recorded by day 12. Hyalomma anatolicum
      anatolicum nymphs were applied on the ears of the calf on day 8 and they dropped
      engorged by days 13 and 14. The resulting adult ticks were examined for the
      presence of T. theileri by severing a leg and making a smear of the clear
      haemolymph which exuded from the wound. The smear was fixed in methanol and
      stained with Giemsa stain. The infection rate with T. theileri in the ticks was
      43.3% (26 out of 60). The intensity of infection was very high and various
      developmental stages of the flagellates were observed (epimastigotes,
      sphaeromastigotes, trypomastigotes and other intermediate stages). The haemolymph
      from 12 ticks was also collected in tissue culture medium and the trypanosomes
      survived for 25 weeks before eventually dying. The results demonstrated
      unequivocally the high vectorial capacity of the tick H. a. anatolicum for T.
      theileri.

PMID- 15732452
TI  - The point prevalence of gastro-intestinal parasites in calves, sheep and goats in
      Magadi division, south-western Kenya.
AB  - Helminths cause great economic loss in livestock in Africa, and can be
      categorized as either direct or indirect losses. Arid and semi-arid lands (ASAL)
      in Kenya comprise 71% of total land area and harbour the largest population of
      cattle, sheep and goats. However, little information on the distribution and
      impact of gastro-intestinal (GIT) parasitism in these animals is available. This
      survey was conducted to establish the prevalence of GIT parasites infecting
      calves, sheep and goats and their relative importance in Magadi division, which
      is semi-arid. Faecal samples were obtained directly from the rectum of 109
      calves, 133 goats and 20 sheep and submitted to the laboratory for faecal worm
      egg counts, and coccidial oocysts examination using a modified McMaster method.
      The significance of differences in mean egg count per gram (epg) between animal
      species and herds (farms) were assessed using analysis of variance. The overall
      prevalence of nematodes in the calves, sheep and goats was 69.2%, 80% and 82%,
      respectively. About 10% of sheep and goats had epgs higher than 1 000, the
      remainder having light to moderate infections. The overall prevalence of
      coccidial oocysts in calves, sheep and goats was 30%, 44% and 45%, respectively.
      Poor productivity in ASAL areas, where nutrition is often poor, is likely to be
      pronounced in the presence of parasite infections. These findings indicate that
      viable internal parasite control should be implemented in the study area in order
      to increase the productivity of the livestock there.

PMID- 15732453
TI  - General morphology of the oral cavity of the Nile crocodile, Crocodylus niloticus
      (Laurenti, 1768). II. The tongue.
AB  - The heads of nine 2.5 to 3-year-old Nile crocodiles (Crocodylus niloticus) were
      obtained from a commercial farm where crocodiles are raised for their skins and
      meat. The animals from which these specimens were obtained appeared clinically
      healthy at the time they were slaughtered. A description of the macroscopic and
      microscopic features of the tongue of the Nile crocodile is presented and the
      results are compared with published information on this species and other
      Crocodylia. The histological features are supplemented by information supplied by
      scanning electron microscopy. Macroscopic features of interest were the dome
      shaped structures grouped in a triangular formation on the posterior two-thirds
      of the dorsum of the tongue. These structures were identified by light microscopy
      to contain well-developed branched, coiled tubular glands and associated lymphoid
      tissue. Other histological features included a lightly keratinised stratified
      squamous surface epithelium supported by a thick layer of irregular dense fibrous
      connective tissue. Deep to this region was a clearly demarcated adipose tissue
      core with a dense mass of striated lingual musculature. Localised thickenings
      were present in the epithelium which were associated with ellipsoid intra
      epithelial structures resembling taste buds.

PMID- 15732454
TI  - Ixodid ticks on dogs in southern Mozambique.
AB  - The objective of this study was to determine the species and distribution of
      ticks infesting domestic dogs in southern Mozambique. To this end 89 collections
      were taken from dogs and the geographic coordinates of the localities at which
      they were made noted. Fifty-eight of these collections were from animals in the
      city of Maputo and 16 from animals at rural settlements close to Maputo. A
      further 15 collections were made from dogs in rural environments north of Maputo.
      Ten ixodid tick species, of which one was only identified to genus level, were
      recovered. Rhipicephalus sanguineus was the most numerous of the ten species, and
      its prevalence and intensity of infestation were significantly higher on city
      dogs than on rural dogs (P < 0.01), whereas the converse was true for
      Haemaphysalis leachi (P < 0.01). Including the city of Maputo, the exact
      localities at which nine tick species were collected, were recorded.

PMID- 15732455
TI  - Effect of urea-molasses block supplementation on grazing weaner goats naturally
      infected with gastrointestinal nematodes.
AB  - The influence of feeding urea-molasses blocks (UMB) on growth and
      gastrointestinal (GI) nematode parasitism of weaner goats grazing the same
      pasture was investigated on a farm in Nyandarua District, Kenya. Thirty female
      Small East African goat kids at an average age of 5 months were initially treated
      with albendazole orally (5 mg kg(-1) body mass) and randomly assigned into one of
      two groups: group I were fed UMB prepared using a cold process and group II kids
      (controls) received no block supplementation (NBS). The UMB were given in the
      evening when the animals returned from grazing and were consumed during the night
      at a rate of 95.0 g head(-1) day(-1). Supplementation was undertaken for 3
      consecutive months from July to September 2001 and January to March 2002. Body
      mass of the kids and faecal egg counts were measured monthly and larval cultures
      were performed on positive faecal samples of kids of each group. Five goats from
      each group were randomly selected for slaughter and total counts and
      identification of worms at the end of June 2002. Significant differences (P <
      0.05) were found in cumulative mass gains of kids in group I from September
      compared with those in group II. On termination of the study kids in group I had
      gained an average of (+/- SD) 20.4 +/- 1.4 kg while those in group II had gained
      11.8 +/- 1.1 kg. From January 2002, faecal egg counts of the kids in the UMB
      group differed significantly (P < 0.05) from those of the NBS group and at
      slaughter, the mean (+/- SD) worm counts for the UMB group was 482 +/- 299 while
      that of the NBS group was 1 302 +/- 410. In all the goats, Haemonchus contortus
      was the predominant nematode recovered. These results indicate that UMB had
      significant effects in the control of GI nematode parasitism and enhanced growth
      of the young goats.

PMID- 15732456
TI  - Parasites of domestic and wild animals in South Africa. XLV. Helminths of dairy
      calves on dry-land Kikuyu grass pastures in the Eastern Cape Province.
AB  - Successive pairs of approximately 4-month-old Friesland bull calves, raised under
      worm-free conditions, were exposed to helminth infection for 14 days on dry-land
      Kikuyu grass pastures at 28-day to monthly intervals, on a coastal farm in a non
      seasonal rainfall region of the Eastern Cape Province. With the exception of one
      pair of calves exposed for 28 days, this procedure was repeated for 28
      consecutive months from December 1982 to March 1985. The day after removal from
      the pastures one calf of each pair was slaughtered and processed for helminth
      recovery and the other 21 days later. Both members of the last four pairs of
      calves were killed 21 days after removal from the pastures. Sixteen nematode
      species were recovered from the calves, and infection with Ostertagia ostertagi
      was the most intense and prevalent, followed by Cooperia oncophora. The calves
      acquired the greatest number of nematodes from the pastures from June to October
      of the first year and from June to August of the second year of the survey. Few
      worms were recovered from the tracer calves examined from November or December to
      March or April in each year of the survey. The seasonal patterns of infection
      with Cooperia spp., Haemonchus placei, Nematodirus helvetianus, Oesophagostomum
      spp., O. ostertagi and Trichostrongylus axei were all similar and were negatively
      correlated to atmospheric temperature and evaporation. Slight to moderate arrest
      in the development of fourth stage larvae occurred from July to September in
      Cooperia spp., April to July in H. placei, and August to October in O. ostertagi
      and Trichostrongylus spp. during the first year of the survey. Too few worms were
      present in the second year to determine a seasonal pattern of arrest. Species
      survival during the hot and windy summer months appeared to be achieved via a
      combination of arrested larval development and an ageing residual population of
      adult worms in the host, and a small extant population of infective larvae on the
      pastures.

PMID- 15732458
TI  - Striped mice, Rhabdomys pumilio, and other murid rodents as hosts for immature
      ixodid ticks as in the Eastern Cape Province.
AB  - Striped mice, Rhabdomys pumilio, were trapped over a period of 17 months in the
      Thomas Baines Nature Reserve, and placed in cages, over water, until all the
      ticks they harboured had detached. The mice were then returned to the reserve.
      Four ixodid tick species were recovered from the mice of which the larvae and
      nymphs of Rhipicephalus follis and Rhipicephalus simus were the most numerous.
      Most larvae of R. follis detached from mice trapped from March to July, and most
      nymphs in March and from June to September. Most larvae of R. simus detached from
      mice trapped from December to March, and most nymphs from January to March and
      during May and June. Seven ixodid tick species were collected from striped mice,
      house rats, Rattus rattus, vlei rats, Otomys spp. and Praomys sp. captured in the
      vicinity of human dwellings or animal holding facilities in the Grahamstown
      district. The striped mice captured in the Thomas Baines Reserve harboured
      considerably larger numbers of ticks than any of the rodent species in the more
      urbanized localities.

PMID- 15732457
TI  - Seasonal prevalence of bovine trypanosomosis in a tsetse-infested zone and a
      tsetse-free zone of the Amhara Region, north-west Ethiopia.
AB  - During a period of four consecutive years, trypanosomosis surveys were conducted
      in a tsetse-infested and tsetse-free area of the Amhara Region of north-west
      Ethiopia. In each study area randomly selected communal cattle were sampled and
      their blood was investigated using parasitological diagnostic methods. At the
      same time the population of biting flies was sampled. The monthly average
      prevalence of trypanosome infections in cattle did not differ significantly
      between study areas. In both study areas, the prevalence of trypanosome
      infections was highest during the long rainy season. Trypanosome infections were
      mainly due to Trypanosoma vivax and they significantly reduced the average packed
      cell volume and the body condition of the animals. The monthly prevalence of
      infection was correlated with the density of biting flies, such as Tabanidae and
      Stomoxys spp., in the preceding month suggesting an important role of mechanical
      transmission in the epidemiology of trypanosomosis in both areas.

PMID- 15732459
TI  - Preliminary survey of ticks (Acari: Ixodidae) on cattle in northern Sudan.
AB  - In a cross sectional survey conducted during the period June 2001 to July 2002,
      the geographical distribution of ticks on cattle in the Sudan was determined.
      Seventeen locations were surveyed from Northern, Central, Eastern, Western, Blue
      Nile and White Nile Provinces. Total body collections of ticks were made from 20
      cattle at each location. Four tick genera and 11 species were identified. The
      tick species collected included Amblyomma lepidum, Amblyomma variegatum,
      Boophilus decoloratus, Hyalomma anatolicum anatolicum, Hyalomma dromedarii,
      Hyalomma impeltatum, Hyalomma marginatum rufipes, Hyalomma truncatum,
      Rhipicephalus evertsi evertsi, Rhipicephalus sanguineus group and Rhipicephalus
      simus simus. Major ecological changes have occurred due to extensive animal
      movement, deforestation, desertification and establishment of large mechanized
      agricultural schemes. These factors have certainly affected the distribution of
      ticks and tick-borne diseases in the Sudan. The absence of A. variegatum and A.
      lepidum in northern Sudan was not surprising, since these tick species are known
      to survive in humid areas and not in the desert and semi-desert areas of northern
      Sudan. The absence of B. annulatus in northern and central Sudan is in accordance
      with the finding that this tick species is restricted to the southern parts of
      the central Sudan. The presence of H. anatolicum anatolicum in Um Benin in
      relatively high abundance is an interesting finding. The present finding may
      indicate that the southern limit of this species has changed and moved southwards
      to latitude 13 degrees N. It is concluded that major changes in tick distribution
      have taken place in the Sudan.

PMID- 15732460
TI  - Larval biology of rhipicephalus (Boophilus) decoloratus (Acarina: Ixodidae) in
      Free State Province, South Africa.
AB  - The objective of this study was to determine certain aspects of the biology of
      Rhipicephalus (Boophilus) decoloratus larvae under laboratory and field
      conditions. Larvae allowed 48 h to select a vertical questing substrate preferred
      90 cm rods in length to those of 60 or 30 cm, while in a separate experiment
      migration from rods 5 cm or 25 cm in length to rods 45 cm in length continued
      between 48 h and 72 h after larval release. Hatching of the larval progeny of
      engorged female ticks exposed to ambient field temperatures during the period
      June to August, occurred synchronously during the third or fourth week of
      November. With a single exception, larvae that hatched during November and
      between April and July survived for 38 days or longer, while those that hatched
      from December to March survived for 31 days or less. Questing larvae were present
      on vegetation throughout the year, with most being recovered during January and
      February. Parasitic larvae were present on cattle from October to May with most
      being collected during January and February.

PMID- 15732461
TI  - Progression towards endemic stability to bovine babesiosis in cattle introduced
      onto a game ranch.
AB  - An opportunity to study progression toward endemic stability to Babesia bigemina
      arose when cattle were reintroduced onto a game ranch in 1999 after an absence of
      three years. The study was conducted between August 2000 and June 2001. The
      unvaccinated breeding cows were sampled only once. Calves born during October
      1999 were initially vaccinated against B. bigemina and Babesia bovis at the age
      of 4 months and were then bled at 10, 17 and 20 months of age. Calves born during
      2000 were bled at 7 and 8 months of age. Sera were collected from all the cattle
      sampled and later tested for antibodies against B. bigemina and B. bovis using
      the indirect fluorescent antibody (IFA) test. Although endemic stability to B.
      bigemina had not been achieved at Nooitgedacht 2 years after resumption of cattle
      ranching, the high seroprevalence in the unvaccinated 8-month-old calves
      suggested that the situation was approaching stability and that calf vaccination
      against bovine babesiosis was not required. Tick control should therefore be
      restricted to prevent excessive tick worry. Only vaccinated cattle were positive
      to B. bovis and it was concluded that the parasite was absent from the ranch.

PMID- 15732462
TI  - Thermodynamic analysis of duplex formation of the heterochiral DNA with L
      deoxyadenosine.
AB  - An L-DNA, the mirror-image isomer of natural DNA, has extraordinary nuclease
      resistance, and thus the molecules should be promising reagents for many
      applications, such as antisense technology. However, little is known about the
      structural and thermodynamic properties of DNAs with this modified nucleotide. In
      this study, we prepared the L-nucleotide (L-dA) and introduced it into
      oligodeoxyribonucleotides to assess the ability of the L-nucleotide as a
      functional molecule for many applications based on the DNA hybridization. Two
      decamers with an L-dA at the center were synthesized and duplexes with the
      complementary DNA strand were applied to structural and thermodynamic analyses.
      The structural study by CD spectra showed that the structures of both modified
      "L/D-D" duplexes were the typical B-form. This result suggests that the global
      structure of DNA was not collapsed by the introduction of an L-DNA. Thermodynamic
      parameters (deltaH degrees, deltaS degrees, and deltaG degrees 37) of the duplex
      formation, determined by UV melting experiments, indicated that the both duplexes
      were destabilized at about 2.5 to 3.0 kcal mol(-1) by the introduced L-dA, mainly
      due to an unfavorable enthalpic effect. In conjunction with information by other
      researchers, these results suggest that the L-DNA affect on the duplex structure
      and the stability vary locally; thus, the thermodynamic stability of modified L/D
      D duplexes should be predictable by the nearest-neighbor thermodynamic
      parameters.

PMID- 15732463
TI  - Theoretical analysis concerning the characteristics of a dye-binding method for
      determining serum protein based on protein error of pH indicator: effect of
      buffer concentration of the color reagent on the color development.
AB  - In the dye-binding method based on protein error of a pH indicator, the color
      development has been reported to be markedly affected by the buffer concentration
      of the color reagent. In this study, the author analyzed this phenomenon by a
      theoretical calculation based on the chemical equilibrium of protein error. The
      calculation was performed on the assumption that both the dissociated dye anion
      and the anion contained in the buffer solution react with protein, forming a dye
      protein complex and an anion-protein complex, respectively. The calculated
      results were compared with those obtained by the experiments using bromophenol
      blue, bromocresol green and bromocresol purple that are employed widely for
      determining the human serum albumin concentration clinically. The calculated
      results of this method are summarized as follows: (1) the color development
      decreases with the increase in the concentration of the anion contained in the
      buffer solution; (2) the calibration curve is more linear in the higher
      concentration of the anion than in the lower one. These calculated results agreed
      well with the experimental ones. From these results, it was concluded that the
      change in the color development by the buffer concentration of the color reagent
      is due to the change in the concentration of the buffer anion.

PMID- 15732464
TI  - Size distribution and characteristics of chemical components in ambient
      particulate matter.
AB  - Ambient particulate matter and gas in Kyoto were investigated by gravimetric
      analysis, X-ray fluorescence spectrometry, and ion chromatography in order to
      clarify their behavior and origin. The size distribution and characteristics of
      the chemical components in ambient particulates collected on PTFE membrane
      filters using an Andersen air sampler were examined from August 2001 to April
      2004. A four-stage filter pack method was used to sample the atmosphere for the
      determination of gas (SO2, HNO3, HCl, NH3) and particulate matter (SO42, NO3, Cl
      , Na+, K+, Ca2+, Mg2+, NH4+) concentrations from October 2002 to April 2004. The
      concentration of SPM mass was in the range of 6.7 - 80.2 microg/m3. The size
      distributions of SPM mass were bimodal, peaking at around 0.65 - 1.1 and 3.3 -
      4.7 microm, and 40 - 85% of SPM mass was fine particles (< 2.1 microm). Na, Mg,
      Al, Si, Ca, Cl, and Fe were mainly present in coarse particles (2.1 to 11.0
      microm), while S was present in fine particles. The concentrations of Al, Si, Ca,
      Mg, and Fe in fine particles increased from March to April in 2002, and those in
      coarse particulates increased in November 2002 and from March to April in 2004.
      This may be the effect of the continental yellow sand "Kosa." The differences in
      the size distributions of Al, Si, Ca, Mg, and Fe in particles may depend on
      differences in their place of occurrence and course of transport from China to
      Japan. The concentration of HCl gas was higher than that of particulate chloride
      ion in summer. Nitric acid gas existed at higher concentrations in summer, but
      fine particulate nitrate ion was observed in winter. The gaseous-to-fine aerosol
      nitrate fraction became higher at warmer temperatures. Coarse sulfate was below
      10%, and SO2 gas and fine particulate sulfate were above 90%.

PMID- 15732465
TI  - Quantitative analysis of chloride in brackish water: an application to the
      hyperchromic effect of copper(II) ion with chloride ion.
AB  - A new modified method was applied to the determination of chloride anion in
      brackish water by using a common copper(II) sulfate solution and a
      spectrophotometer. The result of the quantitative analysis demonstrated that
      chloride concentrations were 1.61% w/v and 1.74% w/v at ebb tide and flood tide,
      respectively, of the Muya River. On the other hand, chloride concentrations were
      1.17% w/v at ebb tide and 1.65% w/v at flood tide of the Yoshino River. The new
      method proved that chloride concentration corresponded well with results from
      Mohr and conductive methods. Therefore, the newly developed method can be
      exploited as common means to measure chloride concentration in aqueous solutions.
      Moreover, it is also valuable for application to other types of environmental
      samples.

PMID- 15732466
TI  - An integrated dual ultramicroelectrode with lower solution resistance applied in
      ultrafast cyclic voltammetry.
AB  - A method for calculating the solution resistance of an integrated dual
      ultramicroelectrode was introduced, and then tested by experiments using dummy
      cells. Then, with the reduction of anthracene on a gold ultramicroelectrode in a
      0.1 M tetraethylammonium tetrafluoroborate/acetonitrile solution as the test
      system, it could be found that the solution resistance of this integrated dual
      ultramicroelectrode was much lower than that of the two-electrode system
      conventionally used. Thus, the compensation level could be improved up to nearly
      100% at a scan rate of 1.34 MV s(-1), while the latter could not. This showed
      that the integrated dual ultramicroelectrode was more suitable for acting as the
      electrode system in ultrafast cyclic voltammetry, especially in a high-resistance
      solution.

PMID- 15732467
TI  - Membrane sensors for the selective determination of thiopental.
AB  - Novel miniaturized polyurethane (PU) membrane sensors in an all-solid state
      graphite support were developed, electrochemically evaluated and used for the
      assay of thiopental drug. The thiopental (T) sensors are based on the formation
      of ion-association complexes of thiopental with copper(II) and cobalt(II)
      bathophenanthroline (bphen) counter anions as electroactive materials dispersed
      in a polyurethane matrix. The sensors show a linear response for thiopental over
      the range of 1 x 10(-1) - 5 x 10(-5) M thiopental at 25 degrees C over the pH
      range 6 - 11 with anionic slopes of -28.7 and -28.3 mV decade(-1) with Cu- and Co
      bphen thiopental membrane sensors, respectively. These sensors exhibit a fast
      response time (25 - 45 s), a low detection limit (5 x 10(-6) M), a long lifetime
      (7 weeks) and good stability. The selectivity coefficients for thiopental sensors
      relative to the number of interfering anions, were investigated. These sensors
      were used for the direct potentiometry of thiopental in a pharmaceutical
      formulation and human serum. Results with mean accuracy of 99.8 +/- 0.5% of
      nominal were obtained, which compare well with data obtained using
      spectrophotometric (UV-Vis) and British Pharmacopoeia (BP) methods.

PMID- 15732468
TI  - Cetyltrimethylammonium bromide-enhanced chemiluminescence determination of uric
      acid using a luminol-hexacyanoferrate(III)-hexacyanoferrate(II) system.
AB  - A chemiluminescence (CL) method using flow injection (FI) was developed for the
      determination of uric acid based on the enhancement chemiluminescence intensity
      of luminol-hexacyanoferrate(III)-hexacyanoferrate(II) in the presence of
      cetyltrimethylammonium bromide and the uric acid species. The linear range was
      7.0 x 10(-10) - 9.0 x 10(-7) M with a detection limit (3sigma) of 2.58 x 10(-10)
      M, which was about two orders of magnitude lower than those reported. The
      proposed method was used for the determination of uric acid in real samples.

PMID- 15732469
TI  - Chiral CE separation of dopamine-derived neurotoxins.
AB  - An enantiomeric separation of dopamine-derived neurotoxins by capillary
      electrophoresis has been developed. Tetrahydroisoquinoline (TIQ), dopamine (DA),
      (R/S)-1-benzyl-TIQ (BTIQ), (R/S)-6,7-dihydroxy-1-methyl-TIQ (salsolinol, Sal),
      and (R/S)-6,7-dihydroxy-1, 2-dimethyl-TIQ (N-methyl-salsolinol, NMSal) were
      studied as model compounds. The CE running buffer (50 mM phosphate buffer at pH
      3.0) contained 1.5 M urea and 12 mM beta-CD as a chiral selector. During
      separation, the (R)-enantiomers formed more stable inclusion complexes with beta
      CD, and thus had a longer migration time than their optical antipodes. It was
      noticed that the recovery rates of these TIQ derivatives were very poor (< 15%)
      during protein precipitation, a procedure widely used for cleaning up biological
      samples. The recovery was significantly improved by pre-mixing the sample with a
      surfactant (e.g., sodium hexanesulfonate or Triton X-100) to reduce the co
      precipitation. The present method in combination with electrospray ionization
      tandem mass spectrometry (ESI-MS/MS) was applied to study samples obtained from
      in vitro incubation of two catecholamines, dopamine and epinine, with aldehydes
      forming neurotoxins including (S)- and (R)-NMSal enantiomers. The later is known
      to induce Parkinsonism in rats.

PMID- 15732470
TI  - Analysis of carbonic acid in water samples by ion-exclusion chromatography with
      pure water as eluent.
AB  - A simple, sensitive and rapid ion-exclusion chromatographic method for the
      simultaneous separation of carbonic acid and short chain organic acids (formic
      acid, acetic acid, and propionic acid) has been developed. A weakly acidic cation
      exchange resin column TSKgel OApak-A was used for the separation; pure water,
      owing to its lower background conductance, was employed as eluent in order to
      obtain high detection sensitivity. A good separation of these weak acids was
      achieved in 16 min. The linear range of the peak area calibration curve for
      carbonic acid was from 3.0 mg/L to 500 mg/L. The conductivity detection limit
      calculated at S/N = 3 was 0.084 mg/L for carbonic acid. The method developed in
      this work was successfully applied to the determination of carbonic acid in
      several environmental water samples without any pretreatment.

PMID- 15732471
TI  - Normal-phase HPLC enantioseparation of novel chiral metal tetrahedrane-type
      clusters on an amylose-based chiral stationary phase.
AB  - In the present work, an amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) chiral
      stationary phase (CSP) was prepared by coating ADMPC on small-particle silica
      gel. This ADMPC-CSP was for the first time successfully applied to separate a
      series of novel chiral metal tetrahedrane-type clusters. Furthermore, the
      influence of a mobile-phase modifier (various alcohols added in the mobile
      phase), including its concentration and structure, and the structures of the
      clusters on the chiral separation and retention was investigated. The results
      suggest that not only the structure and concentration of alcohol in the mobile
      phase, but also the subtle structural differences in racemate can have a
      pronounced effect on the enantiomeric separation and retention.

PMID- 15732472
TI  - Selective extraction, preconcentration and transport studies of thorium(IV) using
      octa-functionalized calix[4]resorcinarene-hydroxamic acid.
AB  - A new calix[4]resorcinarene bearing eight hydroxamic acid groups (C4RAHA) has
      been synthesized and characterized by FT-IR, 1H-NMR and elemental analysis. Its
      analytical properties were investigated, and showed high affinity and selectivity
      toward thorium(IV) in the presence of large quantities of associated metal ions.
      Thorium(IV) was extracted from an ethyl acetate solution of C4RAHA at pH 4.5. The
      lambdamax and molar absorptivity (epsilon) for thorium(IV) were 341 nm and 7120 l
      mol(-1) cm(-1). The complexation of thorium(IV) with C4RAHA has a 4:1
      metal:ligand stoichiometry, which is relatively rare. The extracts were directly
      aspirated in the plasma for ICP-AES measurements for thorium(IV) in the presence
      of a diversified matrix. The system obeyed Beer's law over the range 0.1 - 6.5
      microg ml(-1) of thorium(IV) with a Sandell sensitivity of 0.0325 microg cm(-2).
      The preconcentration factor and overall stability constant evaluated at 25
      degrees C for thorium(IV) were 133 and 15.86, respectively. The complexation was
      characterized by a favorable enthalpy change. A liquid-membrane transport study
      of thorium(IV) was carried out from the source to the receiving phase under
      controlled conditions, and a mechanism of transport proposed. To check the
      validity of the proposed method, thorium(IV) was determined in monazite sand,
      rare earth sand and water samples.

PMID- 15732474
TI  - Sample preparation for evaluation of detection limits in X-ray fluorescence
      spectrometry.
AB  - The influence of analyte mass concentration on determination of detection limits
      in X-ray fluorescence spectrometry has been investigated experimentally. Both the
      total reflection X-ray fluorescence (TXRF) and the conventional energy-dispersive
      X-ray fluorescence techniques have been used to derive the dependence of analyte
      mass concentration on the values of detection limits. Results obtained indicate
      that values of detection limits are optimum, or in other words, they are closer
      to the true detection limit of the technique, when analyte concentrations are in
      the range of 10 times of the detection limit.

PMID- 15732473
TI  - Optimization of a chemical modifier in the determination of selenium by graphite
      furnace atomic absorption spectrometry and its application to wheat and wheat
      flour analysis.
AB  - A method for the determination of total selenium in wheat and wheat flour using
      graphite furnace atomic absorption spectrometry (GFAAS) with palladium/ascorbic
      acid as a chemical modifier was studied. The effects of nickel nitrate,
      palladium/ascorbic acid, and palladium/magnesium nitrate as chemical modifiers on
      the sensitivity in the determination of selenite, selenate and selenomethionine
      by GFAAS were compared. The palladium/ascorbic acid modifier was used for the
      determination of total selenium in wheat and wheat flour, because the oxidation
      states of the selenium ion are not important in the determination. The detection
      limit was estimated to be 1 microg L(-1) (calculated as 3sigma of the blank); the
      calibration curve was linear for the concentration range 5 - 50 microg L(-1) and
      the recovery range was 96.66 - 101.80%. The optimal ashing and atomizing
      temperatures were 1300 degrees C and 2250 degrees C, respectively. The proposed
      method was successfully applied to the determination of total selenium in wheat
      and wheat flour.

PMID- 15732475
TI  - Simultaneous determination of food dyes by first derivative spectrophotometry
      with sorption onto polyurethane foam.
AB  - A simple spectrophotometric method is described for resolving binary mixtures of
      some food dyes: Amaranth, Brilliant Blue, Sunset Yellow and Tartrazine, using the
      first-derivative spectra with measurements at zero-crossing wavelengths.
      Analytical curves are linear up to 20 mg L(-1). Standard deviations of 1.30,
      2.22, 1.93 and 0.81% were obtained for synthetic binary mixtures of 2 mg L(-1) of
      Amaranth, Brilliant Blue, Sunset Yellow and Tartrazine, respectively. Before the
      spectrophotometric measurements, the dyes were sorbed onto polyurethane foam and
      recovered in sodium dodecyl benzene sulfonate solution. Therefore, matrix
      complexity was eliminated and simple spectra were obtained. The method was very
      satisfactorily used for determining the colorants in synthetic mixtures, with
      recoveries in the 96 - 101% range. Detection limit values were dependent on the
      colorant combination investigated. Commercial products containing binary
      combinations of these dyes in different ratios (from 1:1 to 1:8) were analyzed.
      The results were compared with those obtained by HPLC; very similar values were
      found by the two methods.

PMID- 15732476
TI  - Indirect determination of uranium by the on-line reduction and fluorimetric
      detection of cerium(III).
AB  - A novel flow injection method has been developed for the indirect determination
      of uranium by the on-line reduction and subsequent fluorimetric detection of
      cerium(III). A sample solution containing uranium(VI), prepared as a sulfuric
      acid solution, was injected into a sulfuric acid carrier solution and passed
      through a column packed with metal bismuth to reduce uranium(VI) to uranium(IV).
      The sample solution was merged with a cerium(IV) solution to oxidize uranium(IV)
      to uranium(VI) and the cerium(III) generated was then monitored fluorimetricaly.
      The present method is free from interference from zirconium, lanthanides, and
      thorium, and has been successfully applied to the determination of uranium in
      monazite coupled with an anion-exchange separation in a sulfuric acid medium to
      eliminate iron(III). The sample throughput was 25 per hour and the lowest
      detectable concentration was 0.0042 mg l(-1).

PMID- 15732477
TI  - Simultaneous wavelength selection and outlier detection in multivariate
      regression of near-infrared spectra.
AB  - Near-infrared (NIR) spectrometry will present a more promising tool for
      quantitative measurement if the robustness and predictive ability of the partial
      least square (PLS) model are improved. In order to achieve the purpose, we
      present a new algorithm for simultaneous wavelength selection and outlier
      detection; at the same time, the problems of background and noise in multivariate
      calibration are also solved. The strategy is a combination of continuous wavelet
      transform (CWT) and modified iterative predictors and objects weighting PLS
      (mIPOW-PLS). CWT is performed as a pretreatment tool for eliminating background
      and noise synchronously; then, mIPOW-PLS is proposed to remove both the useless
      wavelengths and the multiple outliers in CWT domain. After pretreatment with CWT
      mIPOW-PLS, a PLS model is built finally for prediction. The results indicate that
      the combination of CWT and mIPOW-PLS produces robust and parsimonious regression
      models with very few wavelengths.

PMID- 15732478
TI  - Detection limit estimated from slope of calibration curve: an application to
      competitive ELISA.
AB  - This paper theoretically derives a general rule that while the slope of the semi
      logarithmic plot (Y vs. log X) of a calibration curve varies depending on analyte
      concentration, X, the slope takes a specific value at the detection limit (L(D)).
      This rule holds good irrespective of the shape of the calibration curve (linear
      or non-linear) and in this paper, is applied to competitive ELISA (enzyme linked
      immunosorbent assay). The following relationship is deduced: slope of log-dose
      B/B0 at L(D) = [relative standard deviation (RSD) of blank responses] / 0.13. The
      L(D) obtained from the above-mentioned slope corresponds to the dose at which the
      RSD of dose estimates is 0.3 (= 30%). A commercial kit for 17alpha
      hydroxyprogesterone is taken as an example.

PMID- 15732479
TI  - Evaluation of the membrane-binding properties of the proximal region of the
      angiotensin II receptor (AT1A) carboxyl terminus by surface plasmon resonance.
AB  - The proximal region of the angiotensin II receptor (AT1A) carboxyl-terminus
      (known as helix VIII) is important for receptor function. In this study, we used
      surface plasmon resonance (SPR) to examine the interaction of helix VIII-derived
      peptides with three model lipid membranes. The membrane-binding properties of
      these synthetic peptides, as well as a series of peptide analogues with modified
      amino acid sequences, could be explained by both amino acid sequence and kinetic
      binding data by SPR. The helix VIII peptides showed a higher affinity for lipid
      membranes that contained negatively charged phospholipid, rather than
      zwitterionic phospholipid. The findings of an SPR study may be useful for
      estimating the cooperative binding of intracellular receptor domains with G
      proteins and the components of the lipid bilayer.

PMID- 15732480
TI  - Potassium-selective membrane electrodes based on macrocyclic metacyclophanes
      analogous to calixarenes.
AB  - The tetrabutyl ester derived from 9,16,25,32-tetrahydroxy[3.1.3.1]metacyclophane
      was an excellent ionophore for constructing a K+-selective membrane electrode.
      This ionophore exhibited a much higher selectivity toward K+ than the
      structurally similar potassium ionophore IV commercially available from Fluka. In
      particular, the interference from organic ammonium ions decreased remarkably.
      Potassium ionophore IV possessed oxygen atoms in the ring structure, while the
      present ionophore changed the oxygen atoms to carbon atoms. Thus, the removal of
      oxygen atoms in ring constituents of the metacyclophane acted to reduce the
      interaction with the NH3+ group of organic ammonium ions. The size of the cavity
      of the present ionophore was between those of calix[4]arene and calix[6]arene
      derivatives, which act as Na+ and Cs+ ionophores, respectively, demonstrating
      that the ability to recognize alkali metal cations was strongly cavity size
      dependent. The present K+-selective electrode had less interference from Rb+ and
      Cs+ than an electrode constructed using valinomycin, but suffered greater
      interference from Na+.

PMID- 15732481
TI  - New cadmium(II)-selective electrode based on a tetraazacyclohexadeca macrocyclic
      ionophore.
AB  - A poly(vinyl chloride)-based membrane of 3,4:11,12-dibenzo-1,6,9,14
      tetraazacyclohexadecane with sodium tetraphenyl borate (NaTPB) as an anion
      excluder and dibutylphthalate (DBP), dibutyl(butyl)phosphonate (DBBP), tris(2
      ethylhexyl)phosphate (TEHP) and tributyl phosphate (TBP) as a plasticizing
      solvent mediator was prepared and investigated as a Cd2+-selective electrode. The
      best performance was observed with the membrane having a ligand-PVC-DBP-NaTPB
      composition of 2:25:60:1, which worked well over a wide concentration range (1.6
      x 10(-6) - 1.0 x 10(-1) M) with a Nernstian slope of 29.5 mV per decade of
      activity between pH 2.0 - 6.0. This electrode showed a fast response time of 13 s
      and was used over a period of 4 months with good reproducibility (S = 0.4 mV).
      The selectivity coefficient for mono-, di- and trivalent cations indicated
      excellent selectivity for Cd2+ ions over a large number of cations. Anions such
      as NO3- and SO4(2-) , did not interfere. The membrane sensor has been
      successfully used to determine Cd2+ in real samples.

PMID- 15732482
TI  - Adsorption and desorption properties of trans-resveratrol on cellulose cotton.
AB  - The adsorption and desorption properties of trans-Resveratrol (Res) on the
      cellulose cotton were investigated under various conditions, such as the pH,
      alcohol percentage, temperature and equilibrium times. Moreover, the acidic
      dissociation constants were determined to be pKa1 = 8.01, pKa2 = 9.86 and pKa3 =
      10.5 by a curve-fitting method. Also, it was found that the adsorption depended
      on the temperature and salting effect. On the other hand, the desorptions from
      cellulose were examined using several kinds of water-miscible organic solvents
      (methanol, ethanol, acetone and THF).

PMID- 15732483
TI  - Are foundation trusts succeeding?

PMID- 15732484
TI  - Alison Gadsby a voice from mental health.

PMID- 15732485
TI  - Improving pain management.

PMID- 15732486
TI  - Taking the stigma out of urinary incontinence.

PMID- 15732487
TI  - Breaking down racial barriers.

PMID- 15732488
TI  - Transmission, management and features of norovirus infection.
AB  - Noroviruses cause acute gastroenteritis in humans with outbreaks occurring in a
      variety of settings. It is important that all nurses are aware of this infectious
      disease and how to report it, and understand the management of patients with this
      condition.

PMID- 15732489
TI  - Carpal tunnel syndrome.

PMID- 15732490
TI  - Trimethoprim.

PMID- 15732491
TI  - A guide to using complementary alternative medicines in cancer.
AB  - Many cancer patients use complementary alternative medicines but may be unaware
      of the potential risks. Good communication skills and sensitivity are essential
      to discuss the patient's needs and preferences and suggest solutions that are
      safe and legally defensible.

PMID- 15732492
TI  - Setting up a screening service for abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysms are usually asymptomatic. Rupture is associated with a
      very high mortality. Ultrasound surveillance of aneurysms offers the opportunity
      to select patients suitable for elective repair, avoiding risk of rupture. This
      article reports on how an ultrasound screening programme was set up by a nurse
      specialist rotating through local GP surgeries.

PMID- 15732493
TI  - Psychological issues surrounding paternal perinatal mental health.
AB  - It has become widely accepted that the perinatal period can be a time of
      heightened risk for mental health problems and emotional responses in women.
      However, there has been less research on men in this area and it has remained a
      somewhat neglected area. While perinatal mental health services are increasing
      for women, few exist for men. While the author acknowledges the greater impact
      perinatal mental health problems can have on women, this article explores
      psychological issues relating to paternal perinatal mental health.

PMID- 15732494
TI  - Understanding why routine observations improve practice.

PMID- 15732495
TI  - Nursing homes can enhance your skills.

PMID- 15732496
TI  - [Do liver cells predict the risk of damage by chemical substances?].
AB  - The article reviews the possible responses of liver cells to chemical insult.
      Both the necrosis and different ways of apoptotic death are considered. The
      regulatory role of BCL2/BAX proteins, p53 protein as well as other proteins
      modulating its activity is also described. The controlled proliferation is
      presented which base on transition of fully differentiated hepatocytes from the
      resting Go phase to GI phase of cell cycle. It is triggered by the loss of organ
      mass after extensive necrosis induced by xenobiotics. In this context the
      interrelations between the parenchymal cells (hepatocytes) and nonparenchymal
      cells, intercellular matrix, released growth factors are discussed. Tumorigenesis
      is also mentioned with special emphasis on the cell cycle control points and "run
      away" from apoptosis of some cells despite the serious mistakes present in their
      DNA.

PMID- 15732497
TI  - [Health hazard for medical staff exposed to nitrous oxide].
AB  - The paper briefly reviews available data on occupational exposure to nitrous
      oxide and health consequences in medical staff. Special attention is paid on
      causes of nitrous oxide contamination in occupational environment and monitoring
      its concentrations. On the basis of the epidemiological studies it was
      ascertained that nitrous oxide exerts multiple deleterious effects on human
      organism, especially on fertility, pregnancy, central nervous system and bone
      marrow.

PMID- 15732498
TI  - [The proteolytic activity and the milk coagulative ability of Thermomyces
      lanuginosus strains].
AB  - The aim of this study was the estimation of the proteolytic activity and the milk
      coagulative ability of Thermomyces lanuginosus strains isolated from different
      natural sources. The estimation of proteolytic activity was conducted at 55
      degrees C on the solid medium with casein. The ability to the milk coagulation
      was estimated at temperature range between 25 and 80 degrees C, using culture
      filtrate of isolated strains. The study proved, that all tested strains were able
      to the hydrolysis of casein, but the highest proteolytic activity had strains
      from hazelnuts. The quickest milk coagulation was observed at 55 degrees C.
      Clotted milk had dense consistency and these samples had best colours and nice
      smells.

PMID- 15732499
TI  - [The role of Thermomyces lanuginosus strains in the biodegradation of rapeseed
      oil].
AB  - The aim of this study was the evaluation of the thermophilic fungus Thermomyces
      lanuginosus (syn. Humicola lanuginosa) in the biosynthesis of lipolytic enzymes.
      The investigated material contained 144 strains of this fungus isolated from
      biohumus, garden compost, leaf compost, mushroom compost, hazelnuts and raw
      coffee beans. The incubation was conducted at 55 degrees C on the solid medium
      with 1.5% rape oil. The study proved, that all tested strains were able to the
      hydrolysis of the rape oil. The highest lipolytic activity have the strains
      isolated from the hazelnuts. It was found the significant negative correlation
      between the diameters of the colonies investigated strains and their lipolytic
      activity.

PMID- 15732500
TI  - [Human erythrocyte lactate dehydrogenase activity changes in the presence of some
      alcohol dehydrogenase inhibitors].
AB  - The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH;
      E.C. 1.1.1.1) inhibitors and substrates: cimetidine, 4-methylpyrazole (4MP),
      EDTA, ethanol and methanol on lactate dehydrogenase (LDH; E.C. 1.1.1.27)
      activity. The activity of LDH was spectrophotometrically determined in in-vitro
      prepared diluted hemolysates obtained from human erythrocytes with mentioned
      compounds at the concentrations 0.01, 0.1, 1.0 mM of cimetidine, EDTA, 4MP and
      12.5, 25.0, 50.0 mM of ethanol and methanol. The reaction was conducted at 37
      degrees C in pH 7.5 and changes of optical density was measured at lambda =
      340nm. LDH activity was significantly inhibited by 0.10 mM (p < 0.05) and 1.0 mM
      (p < 0.01) of cimetidine and EDTA. There were no observed any significant changes
      vs. control in LDH activity when 4MP, ethanol or methanol was added to
      environment of reaction.

PMID- 15732501
TI  - [The influence of carcinogenesis in the oral cavity on the level of zinc, copper
      and iron in serum].
AB  - Samples of blood serum originating from the patients with squamous cell carcinoma
      of various parts of the oral cavity (carcinoma planoepitheliale spinocellulare:
      mucosae buccae, fundi oris, linguae, palati molli) were analyzed for presence of
      some microelements (zinc, copper and iron) using the AAS method. The findings
      were compared to amounts of these elements in serum of healthy persons (control
      samples). Significant differences among groups (with cancer and control) were
      qualified using nonparametric U-Mann Whitney test. The mean contents of all the
      analyzed microelements in serum of persons with cancer were higher as compared
      with controls but statistically significant differences were only in case of
      copper and iron.

PMID- 15732502
TI  - [The assessment of the sensitivity of environmental fungi to urea phosphate].
AB  - In this paper the authors presented the influence of various urea phosphate
      doses, 1-12%, on the environmental fungi growth depending on its intensity and
      the type of created spore e.g. (Penicillium italicum, Aspergillusfumigatus,
      Aspergillus niger, Cladosporium resinae, Mucor hiemalis i Rhizopus nigricans).
      The result of urea phosphate effect on fungi was estimated by static culture
      method using dry mass increase change [g. dry mass/ldm3]. The control was created
      by the growth of the above mentioned fungi on the basis of urea phosphate free
      soil. The obtained results were worked out by a statistic method using Duncan's
      test. The tested fungi showed different sensitivity to the various urea phosphate
      doses. In the presence of 1% urea phosphate the fungi sensitivity depended on
      their growth intensity (Aspergillus niger, Mucor hiemalis i Rhizopus nigricans).
      Additionally, the stimulation of fungi growth with rapid vegetative structure
      progress was observed. Independently of their physiological properties,
      significant inhibition of dry mass increase in the range of 3-12% concentration
      urea phosphate was observed. The result of the use of 3% urea phosphate was the
      reduction of dry mass growth of all tested fungi.

PMID- 15732503
TI  - [Immunoaffinity columns and determination of ochratoxin A in cereals by HPLC.
      Part II. Evaluation of extraction using acetonitrile/water].
AB  - Ochratoxin A from wheat and rye grain was extracted with acetonitrile:water
      (60:40). After clean-up of extracts using immunoaffinity columns (IAC),
      ochratoxin was determined by high-performance liquid chromatography using C18
      column and fluorometric detection at 330 nm excitation and 460 nm emission. The
      mean recovery of ochratoxin A at fortification levels 0.1-100 microg/kg, was 74
      89%. The limits of detection (LOD) and quantification (LOQ) were 0.015 and 0.025
      microg/kg, respectively. The positive results were confirmed by reaction with BF3
      complex in methanol.

PMID- 15732504
TI  - [Patulin content in Polish apple juices].
AB  - Patulin content has been evaluated in 754 samples of apple juices bought on
      Polish retail markets in the years 1993-2003. The samples were analyzed by means
      of the HPLC technique with UV detector. Patulin was found above the
      quantification limit (5 microg/l) in more than 22% of the samples. Most of the
      positive results did not exceed the permitted level of 30 microg/l. However, the
      level was exceeded in 8 samples i.e. in 1.1% of the analyzed samples.

PMID- 15732505
TI  - [Recreational activities of Bydgoszcz youth at the age of pubescence].
AB  - The article presents results of inquiry carried out in October 2002 among 498
      pupils selected by chance, from gymnasiums in Bydgoszcz: 297 girls and 261 boys
      aged 14-16. The aim of the inquiry was to distinguish hygiene of recreation of
      young people at the age of pubescence, as well as to show dependence in
      exploiting free time. For statistic evaluation the program of computing sheet
      EXCEL was used. Comprehensive study activities were presented according to stages
      of statistic survey: inquiry theses were prepared, inquiry measures selected and
      adequate inquiry tools chosen--in form of a questionnaire, results of the
      research were completed and statistically worked out, substantial valuation
      carried out and conclusions drown. In declared by the youth interests in sports,
      there are two form of realization: active--through institutional and individual
      practising sport in athletic clubs and centres of recreation and passive--through
      watching tv, looking on, reading press and sports collectorship. Surprising is
      the fact that girls are equal to boys in attending competitions as spectators. As
      expected, the preferable form of activity for boys is riding a bicycle and
      playing football, girls alike boys most willingly ride a bicycle and swim. The
      conception of 'healthy life style' is understood by boys as 'personal hygiene and
      lack of addictions', while girls are of opinion that the most important element
      is sleep, recreation and personal hygiene.

PMID- 15732506
TI  - [100-th anniversary of the Scientific Society of Food Hygiene in Paris].

PMID- 15732507
TI  - On the one hundredth birthday of Dr. Juan Manuel Tato, Buenos Aires, Argentina.
      Pioneer in advancing otorhinolaryngology into modern neurootology.

PMID- 15732508
TI  - Ultra-high-frequency acoustic stimulation and tinnitus control: a positron
      emission tomography study.
AB  - Ultra-high-frequency (UHF) external acoustic stimulation with the UltraQuiet
      device (UQ) has been reported to provide significant relief of severe disabling
      type tinnitus. The nuclear medicine imaging technique of positron emission
      tomography (PET) was selected as a monitoring system to compare objectively
      metabolic alterations in brain function before and after UHF/UQ and to correlate
      the PET data with the subjective behavioral response of patients reporting
      tinnitus relief. PET of brain was completed on 6 patients randomly selected from
      a cohort of 15 patients included in a protocol to establish long-term tinnitus
      relief with UHF/UQ. Twelve specific regions of interest (ROI) were selected for
      PET of brain examination on the basis of results obtained with single-photon
      emission computed tomography (SPECT) of brain examinations recommended for
      patients with severe disabling-type tinnitus and demonstrating significant
      perfusion asymmetries in the right and left brain ROI of the primary auditory
      cortex; frontal, temporal, parietal, and medial temporal lobes; and cerebellum.
      PET of brain results included ratios of post- and pre-UHF/UQ stimulation that
      demonstrated no random response in the selected PET of brain ROI and ratios of
      post- and pre-UHF/UQ stimulation that demonstrated three categories of response
      in the selected PET brain ROI for all six patients: hypermetabolism in three
      patients; hypometabolism in two; and a mixed response in one. Correlation was
      established for each patient among PET and electrophysiological responses of
      alteration in minimal masking levels, the residual UHF neuronal response as
      reflected in the UHF audiogram, and the subjective reported behavioral responses
      of patients (obtained from outcome questionnaires for tinnitus relief, which
      focused on tinnitus intensity, annoyance, severity index, and a subjective scale
      of value of the UHF/UQ device for tinnitus relief. The subjective behavioral
      response for tinnitus relief with UHF/UQ was found to reflect a dual effect:
      acoustic stimulation of the residual neuronal function in the UHF range (10-14
      kHz) and audiometric thresholds of 40-50 dB sound pressure level (SPL), and the
      metabolic activity at brain cortex for neuronal reprogramming. The PET of brain
      categories of response suggested that the UHF/UQ "masking" is predominantly
      reflective of neuronal reprogramming at the brain cortex. Nuclear medicine PET of
      brain imaging has provided an objective monitoring system for attempting to
      establish the efficacy of UHF/UQ for tinnitus relief. No complication of the
      tinnitus was reported secondary to the PET of brain examination. This limited PET
      of brain study supports the clinical recommendation of the efficacy of UHF/UQ
      external acoustic stimulation for a selected population of patients with tinnitus
      of the severe disabling type.

PMID- 15732509
TI  - Quantitative electroencephalography patterns in patients suffering from tinnitus.
AB  - We conducted this study in an attempt to determine whether the
      electroencephalographic activity in patients suffering from tinnitus exhibits
      tinnitus-typical electroencephalography features. Our results indicated a
      significant increase in the average total power in female tinnitus patients and a
      significant decrease in average total power in male tinnitus patients.
      Furthermore, we noted a suppression of the alpha peaks or a split alpha band (or
      both). The reactivity of the alpha frequency was employed to evaluate the
      efficacy of noise generators, a critical component of tinnitus-retraining
      therapy. In conclusion, tinnitus-typical electroencephalography features can be
      extracted from the electroencephalogram.

PMID- 15732510
TI  - Motion sickness: its pathophysiology and treatment.
AB  - The pathogenesis of motion sickness includes both inner-ear stimulation by body
      movement, especially a Coriolis-type stimulus, and optokinetic stimulation due to
      the shift of the surrounding visual fields. According to Kornhuber, Sakata and
      others, the vestibular cerebellum also participates in an important way. We
      conducted this study to elucidate the influence of the vestibular cerebellum on
      the development of motion sickness. We initially focused attention on the visual
      suppression test of Takemori et al. as a test for vestibular cerebellar function.
      We reported a modification of this test, described as postrotatoric nystagmus. We
      employed this test as a rotatoric visual suppression test using milder stimulus
      for patients complaining of motion sickness. The pathogenesis and treatment of
      motion sickness are also discussed.

PMID- 15732511
TI  - Delayed endolymphatic hydrops as a clinical entity.
AB  - Delayed endolymphatic hydrops (DEH) is a clinical entity that can be
      differentiated from Meniere's disease and is typically observed in patients who
      have been suffering from longstanding unilateral profound inner-ear hearing loss.
      DEH probably is caused by delayed atrophy or fibrous obliteration of the
      endolymphatic resorptive system of the membranous labyrinth. The time that
      elapses between the occurrence of hearing loss and the onset of DEH can range
      from 1 to 74 years. The most common cause of hearing loss preceding DEH is
      juvenile-onset unilateral profound deafness (early childhood unilateral profound
      sensorineural hearing loss of unknown etiology), followed by labyrinthitis from
      various causes and physical and acoustic traumas to the inner ear. Two types of
      DEH exist: the ipsilateral type, in which the ear with profound hearing loss
      suffers progressive endolymphatic hydrops, and the contralateral type, in which
      the formation of progressive endolymphatic hydrops takes place in the ear
      opposite to the previously deafened ear. The incidence of the ipsilateral type is
      higher than that of the contralateral type, and the contralateral type is more
      common in older patients. When recurrent episodic vertigo cannot be remedied
      through conservative treatment, labyrinthectomy and vestibular neurectomy on the
      deaf ear are curative for ipsilateral DEH. However, no such surgical treatment is
      available for the contralateral type.

PMID- 15732512
TI  - Stabilization of the head position in pitch plane: study of imbalance during a
      multisegment posturography examination.
AB  - Our purpose was to evaluate head stabilization in pitch plane in patients with
      different kinds of imbalance when standing over firm and movable surfaces. We
      used the STATITEST (Societe Mumedia, Belgium), a multisegment platform for
      recording and computing postural adjustments at different body levels. We
      detected these data by two sensors placed on the head and hip of each subject in
      four situations: eyes open on a firm surface (EOFS); eyes closed on a firm
      surface (ECFS); eyes open on a movable surface (EOMS); and eyes closed on a
      movable surface (ECMS). For each recording, a magnetic field was broadcast by an
      antenna placed in front of the patients. First, as the manufacturer did not
      provide the normal range limits for shoulder sway, we conducted a statistical
      analysis on a population and selected a sample of 31 normal individuals. Second,
      we performed the experiment with 91 patients in two steps: standard examination
      and an assessment with sensors on the head and shoulder. The following values of
      increased head-shoulder relationship were found: on EOFS, 6; on ECFS, 5; on EOMS,
      6; and on ECMS, 11. We noted the predominance of smaller head adjustments,
      reflecting accurate head stability. However, a small percentage of patients
      showed increased head movement, a pigeonlike sway. A correlation of these
      individuals with postural strategies revealed that almost all adopted ankle
      strategies.

PMID- 15732513
TI  - Sequential sound therapy in tinnitus.
AB  - Sequential sound therapy, which uses wide-band white noise distinguished by some
      unique characteristics, is applied in the treatment of tinnitus. The methodology
      is described, as are the differences from and similarities to tinnitus retraining
      therapy. We have performed sequential sound therapy in 26 patients from 2002
      through part of 2003. Thirty-eight generators of sounds were adapted for use in
      this therapy and, of these, 34 incorporated an earphone. The results of
      sequential sound therapy in our 26 patients were compared with the results of
      tinnitus retraining therapy in 15 patients treated during the years 2000 and
      2001. Satisfactory results obtained with sequential sound therapy totaled 100%,
      whereas only 33% of subjects treated with tinnitus retraining therapy obtained
      satisfactory results. In 6 patients who received sequential sound therapy,
      tinnitus disappeared altogether. In addition, no patient receiving sequential
      sound therapy has left the treatment protocol, whereas 53% of patients receiving
      tinnitus retraining therapy abandoned the treatment protocol.

PMID- 15732514
TI  - Acupuncture treatment of whiplash injury.
AB  - We evaluated by computerized static posturography the postural changes after
      acupuncture treatment in a group of 27 patients (12 men and 15 women; mean age,
      35.7+/-6.8 SD) having balance disorders caused by cervical torsion due to
      whiplash injury. Acupuncture was performed by piercing deeply and bilaterally
      acupuncture points bladder 10 and gall bladder 20 with steel needles that were
      twirled manually for 20 seconds. All patients underwent posturographic
      evaluations before and just after each session of acupuncture. The posturography
      was performed with open eyes (OE), closed eyes (CE), and closed eyes with
      retroflexed head (CER). The control group consisted of 25 patients complaining of
      the same symptoms as those recorded by the study group due to whiplash injury but
      treated with nonsteroidal anti-inflammatory drugs and myorelaxation or with
      physiotherapy only. The data presented in this study revealed a considerable
      difference between the two groups as regards the reduction of the CE and CER
      length of the statokinesigram just before each session of acupuncture; the
      frequency oscillation on the sagittal plane in CER was reduced in the study
      group, whereas we noticed a progressive increase of its values in the control
      group. The high percentage of positive results in whiplash injury patients leads
      us to advocate acupuncture for balance disorders due to cervical pathology.

PMID- 15732515
TI  - Pulsatile tinnitus and carotid artery atherosclerosis.
AB  - This cross-sectional study was designed to determine the prevalence of carotid
      artery atherosclerosis in patients with pulsatile tinnitus. All patients who had
      pulsatile tinnitus and presented to the otolaryngology clinic of Rasoul Akram
      Hospital, Iran University of Medical Sciences, and to some other private
      hospitals and clinics were referred to a tertiary referral center. From November
      1999 to September 2003, 34 patients with pulsatile tinnitus underwent a clinical
      evaluation. Color Doppler ultrasonography was performed in all patients.
      Atherosclerotic carotid artery disease (ACAD) was found to be a cause of
      pulsatile tinnitus in four patients (11.76%). The mean age of these patients was
      higher than that of the other patients (59 vs. 34 years). All patients had at
      least one risk factor for ACAD. In three patients, pulsatile tinnitus was the
      first manifestation of ACAD; in two of these, this symptom occurred when the
      stenosis affected more than 70% of the artery's diameter. ACAD should be
      considered in evaluation of all patients with pulsatile tinnitus and associated
      cardiovascular risk factors. As pulsatile tinnitus may be the sole manifestation
      of severe carotid artery stenosis, immediate color Doppler ultrasonographic study
      is recommended in those patients with risk factors and in the elderly.

PMID- 15732516
TI  - Management of idiopathic sudden sensorineural hearing loss: experience in newly
      developing Qatar.
AB  - Idiopathic sudden sensorineural hearing loss is a medical emergency that requires
      urgent diagnosis and treatment, and the adaptation of a proper protocol for
      management is a priority. In most cases, such treatment is rather controversial
      and depends on a variety of factors. The aim of this study was to determine and
      identify as early as possible those factors that play the important role in the
      prognosis of the condition, to describe the experience, and to suggest a
      treatment protocol that can be adopted in a tertiary hospital, such as Hamad
      General Hospital. Our study was retrospective and descriptive. It was conducted
      in the ear, nose, and throat outpatient clinics at Hamad General Hospital and the
      ear, nose, and throat wards at Rumailah Hospital. We enrolled a total of 21
      patients with idiopathic sudden sensorineural hearing loss. The treatment
      protocol that was adopted--consisting of high-dose steroid therapy, full-dose
      antiviral drug (acyclovir), and a histamine analog, betahistine--resulted in
      hearing improvement in 57.4% of cases. Then the possible good and bad prognostic
      factors were discussed. The results of our study revealed that the steroid
      therapy protocol practiced in Qatar resulted in hearing improvement in patients
      with idiopathic sudden sensorineural hearing loss. Good prognostic factors
      include early diagnosis, marked reduction of symptoms, and improved shape of the
      audiometric curve.

PMID- 15732519
TI  - Investigation of Betaserc in auditory and vestibular disturbances.
AB  - Vestibular vertigo is a primary symptom in neurootological clinical practice and
      is common among cerebrovascular diseases. The aim of this investigation was to
      evaluate the effect of betahistine dihydrochloride (Betaserc), 8 and 16 mg, on
      patients who were transport system workers with vascular auditory and vestibular
      disturbances. We examined 50 patients, 30 of whom were treated with 16-mg doses
      and 20 of whom received 8-mg doses of Betaserc. The mean age of the patients was
      37+/-2.3 years. The following evaluative methods were used: questionnaire
      including detailed neurootological history; ear, nose, and throat and
      neurological examinations; tonal threshold audiometry; and examination of the
      vestibular system (spontaneous and provoked reactions). On the basis of the
      investigations carried out, we recommend 16 mg Betaserc three times daily in the
      acute phase. The medication is very well tolerated, has no sedative effect and is
      suitable for long-term treatment.

PMID- 15732517
TI  - Tinnitus evoked by speech.
AB  - Modulation of tinnitus by a variety of somatosensory stimuli and alteration of
      gaze has been described. We present two cases of tinnitus induced by speech
      (voice). The tinnitus was troublesome in both patients, and both had hearing loss
      and ischemic changes in the central nervous system documented by magnetic
      resonance imaging. We discuss cross-modal plasticity and how it may explain the
      tinnitus in these two patients.

PMID- 15732518
TI  - The incidence of tinnitus in people with disorders of the temporomandibular
      joint.
AB  - This study was conducted to compare the prevalence of tinnitus in the general
      population with its incidence in people with dysfunction of the temporomandibular
      joint (TMJD) within the temporomandibular disorder (TMD) population. Earlier
      studies had indicated the prevalence of tinnitus in the general population to be
      in the range of 10-14%. Between 1981 and 1990, analysis of 989 consecutive TMJD
      patients from a TMD database found the incidence of tinnitus to be 7.28% (72
      patients). In addition, no statistical difference was found between the
      occurrence of tinnitus in men and women. Thirty-nine patients of the tinnitus
      group (54.17%) claimed to have pain in the ear as compared to 318 patients
      (32.15%) in the total population. No patient with tinnitus claimed to have
      decreased hearing, whereas three patients (0.30% of the total population)
      complained of a decrease in hearing.

PMID- 15732520
TI  - Outcomes from Clarion implantation in India.
AB  - We evaluated the results of the use of Clarion (Advanced Bionics, USA) implants
      in 30 Indian patients. Cases included in the study were prelingual and
      postlingual patients in whom the cochlea was normal and prelingual patients in
      whom the cochlea had a Mondini defect or was ossified. We found that multiple
      speech strategies available with the Clarion implant were a distinct advantage.
      The postlingual patients fared better with speech discrimination in noise using
      the high-resolution strategy, and young prelingual patients developed hearing and
      speech faster using simultaneous analog stimulation and multiple pulsatile
      stimulation strategies. Moreover, in Mondini cases, all electrodes could be
      inserted using the enhanced bipolar device.

PMID- 15732521
TI  - Betahistine in vertebrobasilar insufficiency.
AB  - The aim of this study was to observe the usefulness of betahistine
      dihydrochloride--Betaserc--in therapy for vestibular disorders in patients with
      vertebrobasilar insufficiency. Two groups of patients, in each of which were 150
      patients (mean age, 52.2 years), were tested on the basis of videonystagmography
      and stabilometry. Betaserc was administrated in two separate doses: 8 mg three
      times daily and 16 mg three times daily for 120-180 days (mean, 132 days). In
      every case before and after therapy, visuo-oculomotor and vestibulo-oculomotor
      reflexes were tested, and amplitude and velocity of the sway were measured during
      dynamic posturographic testing. After Betaserc treatment, pathological visuo
      oculomotor reactions and pathological cervical test results disappeared in most
      cases: Smooth pursuit improved in 59.9% of cases and saccadic movements in 55.9%
      of patients, and cervical nystagmus disappeared in 62.2% of tested people. During
      stabilometry, mean and maximal platform amplitude and mean head velocity
      decreased as compared with results from tests performed before treatment. These
      observations were significant after the greater dose of Betaserc; nonetheless,
      improvement was noted after both doses. The usefulness of Betaserc in
      vertebrobasilar insufficiency was proved, 4-6 months' therapy was sufficient, and
      the effect on central compensation seemed to be most probable.

PMID- 15732522
TI  - Transient interruption of unilateral tinnitus by fentanyl and propofol in a
      patient with neuromuscular disorder.
AB  - A 64-year-old man with left-sided tinnitus since September 2003 underwent left
      atrial catheter ablation for atrial flutter that he had been experiencing since
      1999. For the procedure, he was anesthetized with a cumulative intravenous dosage
      of 700 mg propofol and 0.5 mg fentanyl over 2.5 hours. The patient's tinnitus had
      completely disappeared after he awoke from the anesthesia. Ten days after the
      procedure, however, tinnitus recurred. In conclusion, high-dose intravenous
      fentanyl and propofol transiently discontinue unilateral, idiopathic tinnitus.
      The observed effect may have implications for the treatment of tinnitus.

PMID- 15732523
TI  - Long-term follow-up of tinnitus in patients with otosclerosis after stapes
      surgery.
AB  - We prospectively studied 48 otosclerosis patients over a 2-year interval. Forty
      four had stapedotomy, and four had stapedectomy. Demographics, clinical history,
      and pre- and postoperative audiometry results were recorded. A questionnaire
      asking about tinnitus (intensity, pitch) and including a visual analog scale
      quantifying the degree (1-10) of annoyance caused by the tinnitus was completed
      pre- and postoperatively (4-10 months and 14-48 months, respectively). Ninety-one
      percent of the otosclerosis patients reported the presence of tinnitus, and
      39.58% reported severe disabling tinnitus (SDT; 7-10 on the visual analog scale).
      High-pitch (whistle) tinnitus was present in most patients, and white noise
      (radio static, waterfall, rain) was present in others. No patient described the
      tinnitus as a low-tone noise (buzzing). Ninety-one percent of patients reported
      tinnitus reduction or total remission after surgery. Ten of 19 patients with SDT
      reported complete remission of tinnitus, 7 reported improvement postoperatively,
      and 2 reported no change. No patient reported worsening of tinnitus. Small
      postoperative air-bone gaps (four tonal average) correlated with remission or
      reduction of tinnitus in SDT patients. Tinnitus pitch, gender, and age of
      patients were not related to decrease of tinnitus postoperatively. A larger
      preoperative air-bone gap correlated with larger reduction of tinnitus after
      successful surgery. A lower preoperative bone conduction level correlated with
      more intense tinnitus before surgery and greater reduction postoperatively. We
      contacted 25 patients from 14 to 48 months after surgery, and all reported that
      their tinnitus status had not changed since the early follow-up. Tinnitus is very
      prevalent in otosclerosis patients; almost one-half of patients have SDT
      preoperatively, and stapes surgery improves this symptom in 91% of cases.
      Preoperative air-bone gap and bone conduction level and a postoperative airbone
      gap seem to influence the degree of postoperative tinnitus reduction.

PMID- 15732524
TI  - Prospects for a group A streptococcal vaccine.
AB  - Group A streptococcal (GAS) infections are associated with a number of human
      diseases, including pharyngitis, impetigo, necrotizing fasciitis, streptococcal
      toxic shock syndrome and rheumatic heart disease. An increase in the incidence of
      severe GAS infections in Western countries, and the awareness of the burden of
      GAS-associated diseases in developing nations, which remains high in spite of the
      availability of antibiotics, has provided the impetus for development of a safe
      and efficacious GAS vaccine. This has focused on the M protein, a major GAS
      virulence factor, however, with the publication of several GAS genomes, a number
      of non-M vaccine candidates are now under investigation.

PMID- 15732525
TI  - New directions towards safer and effective vaccines for Alzheimer's disease.
AB  - The first experimental vaccine against Alzheimer's disease caused encephalitis in
      some patients, which led to termination of the clinical trial and dealt a serious
      blow to this therapeutic approach. With second-generation vaccines that are
      likely to circumvent this side effect, this type of therapy remains promising,
      although more extensive animal studies are likely to be required before approval
      of other clinical trials. Another potential side effect, microhemorrhages within
      the brain vasculature, has been observed in mouse models following passive
      immunization, but has not been assessed in reports of active vaccination.
      Together, these serious adverse reactions emphasize the need to test potential
      Alzheimer's immunotherapy in large cohorts of primate models prior to, or at
      least concurrently with, human trials, as no effective therapy exists for the
      disease.

PMID- 15732526
TI  - Cell-based protein vaccines for influenza.
AB  - An overview of influenza vaccines in development is provided, with an emphasis on
      new cell-based protein vaccine candidates. The current licensed vaccine is a cost
      effective means to reduce the impact of influenza with a known mechanism of
      action. Most vaccine companies are focusing on the production of whole influenza
      viruses in various cell lines to replace egg-based manufacturing technology. Only
      a limited number of targets have been identified for the development of cell
      based protein influenza vaccines. They include hemagglutinin, neuraminidase, M2
      and nucleocapsid protein. These protein-based vaccine candidates are discussed,
      along with their progress in clinical development and the advantages and
      disadvantages of each vaccine approach.

PMID- 15732527
TI  - Novel immunotherapeutic approaches to prostate cancer.
AB  - Immunotherapy offers new and exciting therapeutic options for patients with late
      stage prostate cancer. While the concept of using the immune system to combat
      cancer is not new, it is only in this post-genomics era that the realistic
      possibility exists of effectively harnessing the immune system against disease.
      Immunotherapies can be loosely divided into three major categories: non-specific
      immune stimulation, specific target antigens and whole-cell approaches. All three
      systems have merits and drawbacks, although the goal of overcoming 'self'
      tolerance is common to all of them. This review highlights some of the more
      recent experiments in each of these three fields, focusing particularly on
      prostate cancer. We suggest that it is unlikely that one single cancer antigen
      exists and that recent data support this by showing that strong immune responses
      to prostate antigens can be elicited in a variety of ways. Therefore, a
      multivalent approach is likely to be most clinically efficacious. Data gathered
      from the past three years are discussed in this review and lead to the
      inescapable conclusion that immunotherapy is now a reality.

PMID- 15732528
TI  - Dendritic cell vaccines and obstacles to beneficial immunity in glioma patients.
AB  - The dismal prognoses suffered by malignant primary brain tumor (glioma) patients
      remain unchanged over the past two decades, despite significant improvements in
      the treatment of distinct tumors. Dendritic cell-based vaccine therapies
      represent a promising experimental approach to treat malignant gliomas, but major
      challenges still remain to render vaccination more effective. These challenges
      include diminishing the risk of pathological autoimmunity, identifying the
      cellular basis of clinical vaccine benefits and increasing the proportion of
      patients experiencing such benefits. Over the past three years, studies in glioma
      patients have characterized tumor antigens on human gliomas, identified some of
      the immune cells involved in beneficial anti-glioma immunity and examined how
      gliomas may be altered by sub-lethal immune influences, providing a glimpse of
      the strength with which immunity influences glioma clinical outcome. This
      progress promises to improve clinical vaccines for glioma, and perhaps for other
      cancers.

PMID- 15732529
TI  - Engineering T-cells with antibody-based chimeric receptors for effective cancer
      therapy.
AB  - The combination of power and specificity inherent within the immune system make
      its manipulation an attractive prospect for the development of novel anticancer
      therapies. However, tumors are frequently poorly recognized by the immune system,
      and intrinsic controls limit the benefit from active immunization. These and
      other issues have proved major challenges in the search for effective cancer
      immunotherapy. Recent advances in the understanding of the immune system and the
      development of methods to manipulate it have led to the point where engineered T
      cell therapy can be tested in the clinical setting with a realistic chance of
      success. These advances are considered and potential future clinical and
      scientific issues involved in the successful development of effective, engineered
      T-cell therapy are examined.

PMID- 15732530
TI  - Modulation of the notch pathway for immunotherapy.
AB  - Since its initial description as a neurogenic locus in Drosophila, the Notch
      pathway has been shown to play a central role in cell fate decisions across
      species, including vertebrates, guiding the differentiation of multiple cell
      types. In the immune system, its function was first demonstrated during
      lymphopoiesis, but in recent years this pathway has been shown to still be active
      in peripheral T-cells. Therapeutic opportunities that could arise from the
      manipulation of Notch signaling in immune disorders such as autoimmunity, allergy
      and in cancer immunotherapy and transplantation are discussed.

PMID- 15732531
TI  - Recent advances in the development of live, attenuated bacterial vectors.
AB  - Over the last quarter century, scientific advances have created new tools and
      technologies to improve the safety and efficacy of vaccines. These improvements
      are spurred by social and commercial needs to enhance existing vaccines or to
      create new ones against an expanding spectrum of diseases. Vaccines based on
      live, attenuated, pathogenic bacteria were originally developed to prevent
      infection by homologous pathogens. More recently, strategies have been developed
      to use these bacterial vaccines as vectors to deliver a variety of protective,
      vaccine antigens via the mucosal route. These approaches are being developed to
      protect not only against heterologous microbial infections, but also against non
      traditional threats such as biowarfare and cancer. These strategies and their
      application to the recent development of delivery systems for use in humans will
      be discussed.

PMID- 15732532
TI  - Adjuvanticity of anti-cD40 in vaccine development.
AB  - CD40 antibodies can be effective adjuvants for humoral and cell-mediated immune
      responses. As their mode of action is not via toll-like receptors, these
      adjuvants can avoid many of the side effects associated with other adjuvants that
      function through these receptors. CD40 antibodies can be effective in high doses,
      administered separately from antigen, or in very low doses conjugated to the
      antigen. In the former case, there are likely to be side effects such as
      splenomegaly, while in the case of conjugates, side effects may be avoided.

PMID- 15732533
TI  - Technology evaluation: colostrinin, ReGen.
AB  - ReGen Therapeutics is developing Colostrinin, a polypeptide complex derived from
      ovine colostrums, for the potential treatment of Alzheimer's disease. The
      compound is currently undergoing phase II clinical trials.

PMID- 15732534
TI  - Technology evaluation: SB-485232, GlaxoSmithKline.
AB  - GlaxoSmithKline (formerly SmithKline Beecham), under license from Hayashibara, is
      developing SB-485232, a recombinant human interleukin-18 cancer immunotherapy for
      the potential treatment of immunologically sensitive cancers, including melanoma
      and renal cell cancer. The compound is currently undergoing phase II clinical
      trials.

PMID- 15732535
TI  - Caring for self: becoming a healing presence.

PMID- 15732536
TI  - Leadership profile: AHNA president Sonja Simpson.

PMID- 15732537
TI  - Self-care through expressive art.

PMID- 15732538
TI  - Networkers actively promoting AHNA.

PMID- 15732539
TI  - AHNA joins in national collaboration in Geriatric Nursing.

PMID- 15732540
TI  - Aromatherapy for health professionals. Holistic practices help with life
      transitions.

PMID- 15732541
TI  - Legal troubles for Wisconsin nurse. Interview with Barbara Lemke [interviewed by
      Carol Deards].

PMID- 15732542
TI  - Dramatic diet change is self-care for Ohio member.

PMID- 15732543
TI  - Simply connecting 'Down Under' Style. AHNA represented at Australian conference.

PMID- 15732544
TI  - Orthodontic extrusion of an extensively broken down anterior tooth: a clinical
      report.
AB  - A predictable esthetic restoration is not limited to the restored teeth; it has
      to include the gingival unit and its interface with the teeth involved. Failure
      to deliver restorations that maintain gingival health jeopardizes the success of
      any restorative procedure and creates potential for periodontal problems.
      Perforations, fractures, root resorption, or caries in the cervical area of the
      tooth, especially in the anterior part of the mouth, present many challenges to
      the clinician. Failure to place the crown margins on sound tooth material may
      violate the biologic width and should be considered a restorative failure.
      Orthodontic root extrusion or forced eruption is a well-documented clinical
      method for altering the relation between a nonrestorable tooth and its attachment
      apparatus, elevating sound tooth material from within the alveolar socket. It has
      some advantages over surgical crown lengthening, which is less conservative
      considering the sacrifice of supporting bone and the negative change in the
      length of the clinical crowns of both the tooth and its neighbors. This article
      presents a case of a maxillary right lateral incisor, extensively broken down
      following trauma, treated with orthodontic extrusion combined with gingival
      fiberotomy, without a need for a corrective surgical procedure.

PMID- 15732545
TI  - Selected characteristics of a new polyvinyl siloxane impression material--a
      randomized clinical trial.
AB  - OBJECTIVES: This study evaluated the ability of a new polyvinyl siloxane
      impression material (Affinis, Coltene/Whaledent, material A) to obtain final
      impressions free of bubbles and voids for indirect fixed cuspal-coverage
      restorations. The results were compared to a control polyvinyl siloxane
      impression material (material B). Both materials were handled by inexperienced
      clinicians (undergraduate dental students) in student clinics. METHOD AND
      MATERIALS: One-hundred and thirty patients who were treated in the Louisiana
      State University School of Dentistry Junior Student Clinic for indirect fixed
      cuspal-coverage restorations and who met the inclusion criteria were randomly
      assigned to either one of two treatment groups, group A (n = 65) or group B (n =
      65). Two calibrated examiners evaluated the first impression of prepared
      posterior teeth at a magnification of 10x for acceptability (no voids or
      bubbles). Position of tooth, type of preparation, preparation finish line (Class
      I-V), and gingival bleeding scores were recorded. All statistical tests were
      performed with the level of significance set at .05. RESULTS: The Fisher-Freeman
      Halton test did not reveal significant associations between material and gingival
      bleeding score (P = .492). Significant differences in the location of the
      preparation finish line between materials were observed (P = .0096); material A
      was more frequently used in cases where the preparation finish line was located
      at least 2 mm subgingivally. Logistic regression was used to assess the effect of
      the material on the success of the impression (acceptable/ unacceptable).
      Material was highly significant in the logistic model (P < .001) with an odds in
      favor of an acceptable impression being eight times higher with material A than
      with material B (odds ratio = 8.00; 95% confidence index for odds ratio: 2.832,
      22.601). The 60/65 (92.3%) impressions made with material A and 39/65 (60%)
      impressions made with material B were rated "acceptable." CONCLUSION: The new
      polyvinyl siloxane impression material provided a significantly higher proportion
      of impressions free of bubbles and voids than the control polyvinyl siloxane
      material.

PMID- 15732546
TI  - Five-year follow-up with Procera all-ceramic crowns.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical performance of
      Procera AllCeram crowns placed over a 5-year period at three different private
      dental practices. METHOD AND MATERIALS: Two hundred five Procera AllCeram crowns
      (50 anterior and 155 posterior) were evaluated in a prospective study from a
      minimum of 6 months to a maximum of 60 months, with a mean of 23.52 months.
      RESULTS: A restoration was considered to be a failure when it impaired esthetic
      quality or function, thus necessitating remake of the crown. The survival rate
      was determined with the use of the Kaplan-Meier survival rate, which gave an
      overall survival rate of 96.7% (100% for the anterior crowns and 95.15% for the
      posterior crowns). CONCLUSION: The Procera AllCeram system seems to have a good
      prognosis for the posterior teeth and an excellent one for the anterior teeth.

PMID- 15732547
TI  - Osteoporosis: the dentist's role in assessing patient risk.

PMID- 15732548
TI  - Risk stratification and dental management of the patient with cardiovascular
      diseases. Part I: Etiology, epidemiology, and principles of medical management.
AB  - The heart pumps blood through a system of blood vessels under the control of an
      electric conduction system to deliver oxygen to all cells of the body. When the
      blood volume becomes greater than the limited volume capacity of the vascular
      system, the patient develops hypertension. When the myocardium does not get
      enough oxygen because of coronary artery disease, the patient will experience
      angina pectoris. If oxygen deprivation to the myocardium persists, the patient
      may develop myocardial infarction. When the conduction system malfunctions,
      arrhythmias occur and the heart is unable to pump blood through the vascular
      system at a regular rate and rhythm. When the heart is no longer able to pump
      enough blood to meet the metabolic demands of the body for oxygen, the patient is
      said to have developed heart failure. In addition, many of the above conditions
      can lead to thromboembolic complications. These cardiovascular diseases are the
      leading cause of death in the United States and most other Western countries. In
      the United States alone, more than 1 million annual deaths and as many as three
      times that number of serious consequences can be attributed to these conditions.
      To provide care to patients with cardiovascular disease, oral health care
      providers must understand the disease, its treatment, and its impact on the
      patient's ability to undergo and respond to dental care.

PMID- 15732549
TI  - Diastema closure with freehand composite: controlling emergence contour.

PMID- 15732550
TI  - Clinical long-term survival of two-retainer and single-retainer all-ceramic resin
      bonded fixed partial dentures.
AB  - OBJECTIVES: All-ceramic resin-bonded fixed partial dentures (RBFPDs) were
      introduced as a conservative treatment approach 15 years ago. The purpose of this
      prospective study was to evaluate the long-term clinical survival of RBFPDs made
      with a conventional two-retainer design or a cantilever single-retainer design.
      METHOD AND MATERIALS: A total of 37 anterior RBFPDs were made from the glass
      infiltrated alumina ceramic In-Ceram. Sixteen RBFPDs with a conventional two
      retainer design were inserted in 14 patients, and 21 RBFPDs with a cantilever
      single-retainer design were inserted in 16 patients. Panavia or Panavia 21 were
      used as luting agents either after silica-coating and silanation or after air
      abrasion only. Patients were recalled every year for a clinical examination to
      evaluate the restorations with regard to function and possible failures. The mean
      observation time in the two-retainer group was 75.8 months, and in the single
      retainer group it was 51.7 months. RESULTS: No restoration debonded. In the two
      retainer group, one restoration was lost because it fractured after 3 months at
      both connectors and one restoration was removed alio loco accidentally. Also in
      this group, four RBFPDs fractured within 15 months after insertion at one
      connector, but the pontic remained in situ as a cantilever RBFPD for several
      years. In the single-retainer group, only one FPD fractured and was lost 48
      months after insertion. The 5-year survival rate was 73.9% in the two-retainer
      group and 92.3% in the single-retainer group. When unilateral fracture of a FPD
      was taken as criterion for failure, the five-year survival rate decreased to
      67.3% in the two-retainer group. CONCLUSIONS: Cantilever all-ceramic resin-bonded
      fixed partial dentures made from high-strength oxide ceramics present a promising
      treatment alternative to two-retainer RBFPDs in the anterior region.

PMID- 15732551
TI  - Periapical actinomycosis: a review.
AB  - Actinomycosis has increasingly been recognized as a cause of persistent or
      recurrent periapical disease associated with endodontically treated teeth. This
      case report shows the classic clinical picture of periapical actinomycosis:
      persistent periapical disease with recurrent sinus tracts. Although there was no
      pain or swelling after clinically acceptable initial endodontic treatment, a
      periapical lesion developed. After retreatment, the periapical lesion persisted,
      and a sinus tract developed. The sinus tract healed with antibiotic therapy but
      recurred within a few months. This cycle of sinus tract to antibiotic therapy to
      recurrence of the sinus tract repeated several times over a period of 5 years.
      Upon biopsy, periapical actinomycosis was diagnosed, where classic "sulfur
      granules" were demonstrated in the histologic examination of the periapical
      lesion. Antibiotic therapy for a period of 6 weeks was prescribed subsequent to
      the histologic diagnosis because of the possibility of spread of the
      actinomycotic infection into the maxillary sinus. Considerable healing was
      evident within 5 months of surgical and antibiotic treatment.

PMID- 15732552
TI  - Chronic periapical periodontitis.

PMID- 15732553
TI  - Thromboembolic disease related to air travel: what you need to know.

PMID- 15732554
TI  - Case of the season: glucagonoma syndrome.

PMID- 15732555
TI  - How chest CT for the diagnosis of pulmonary embolism (PE) has changed my
      professional life: reflections from a PE doctor.

PMID- 15732556
TI  - CT angiography with multidetector-row CT for detection of acute pulmonary
      embolus.

PMID- 15732557
TI  - CT pulmonary angiography for acute pulmonary embolism: cost-effectiveness
      analysis and review of the literature.
AB  - Pulmonary embolism (PE) continues to be a diagnostic challenge. Clinical
      assessment tools, D-dimer testing, ventilation perfusion (V/Q) scanning,
      ultrasound of the lower limbs, computed tomography (CT), and pulmonary
      angiography are all adequate methods used in the diagnosis of acute PE. With
      several options available to physicians, variation in regional costs and
      practices, and conflicting views on imaging modality performance data, there is
      considerable uncertainty regarding the most cost-effective strategy. Cost
      effectiveness analysis is a helpful tool for determining the most effective
      diagnostic strategy when several viable options exist. Although limited by a
      number of necessary assumptions, cost-effective analyses offer a feasible
      solution to a diagnostic process by using an evidence-based approach. Current
      evidence shows that CT is a cost-effective alternative to V/Q scanning,
      particularly when sensitivity is sufficiently high. The purpose of this article
      is to review the cost-effective role of CT in the diagnosis of acute PE.

PMID- 15732558
TI  - Severity assessment of acute pulmonary embolism: role of CT angiography.
AB  - Helical CT has gained wide acceptance in the noninvasive diagnosis of acute
      pulmonary embolism (APE) and has therefore largely replaced conventional
      pulmonary angiography as well as ventilation perfusion scan in the work-up of
      patients suspected of nonsevere pulmonary embolism (PE). Massive PE is life
      threatening; its occurrence may require aggressive treatment such as thrombolysis
      or embolectomy. Identification of patients suffering from major thromboembolic
      events based solely on clinical grounds may, however, be difficult. Acute right
      heart failure is the principal cause of circulatory collapse and death for
      patients with massive PE, and rapid and specific diagnosis and therapy are
      required in such patients. Bedside echocardiography, a commonly performed first
      line examination, demonstrates signs of cor pulmonale, if present, and can
      identify large central thrombi. However, echocardiography has limitations. In
      this review, our goal is to discuss the potential role of CT in assessing
      patients with severe APE. CT evaluation is based on the direct quantification of
      pulmonary arterial bed obstruction using various scores and the evaluation of
      morphological heart changes indicating acute cor pulmonale.

PMID- 15732559
TI  - Imaging of deep venous thrombosis in suspected pulmonary embolism.

PMID- 15732560
TI  - Imaging of chronic thromboembolic pulmonary hypertension.

PMID- 15732561
TI  - MDCT pulmonary angiography: image processing tools.
AB  - The postprocessing of multidetector row computed tomography (MDCT) data sets is
      best termed "volume interrogation." Most techniques are best applied as problem
      solving tools rather than as preset protocols, and radiologist involvement is
      essential. The ability to interact with an isotropic or nearly isotropic data set
      in near real-time is a tremendous advance, but is one that radiologists must
      rapidly embrace and master. This review begins with a discussion of the basic
      postprocessing tools relevant to the analysis of the pulmonary vasculature and
      proceeds to illustrate the clinical application of these techniques to the MDCT
      of acute and chronic thromboembolic disease. It is clear that in the era of MDCT,
      axial image review alone is rapidly becoming not only impractical, but also
      suboptimal. Reformatted images are also beneficial as communication tools for our
      referring colleagues and can enhance the role of the radiologist as part of the
      clinical team.

PMID- 15732562
TI  - Approaches to CT perfusion imaging in pulmonary embolism.
AB  - Computed tomography (CT) has become an increasingly accepted technique and is the
      method of choice for direct visualization of pulmonary emboli (PE). The
      quantitative assessment of tissue perfusion may yield more important information
      for patient management than the direct visualization of emboli by CT alone.
      Several attempts have been made to measure pulmonary blood flow by administration
      of intravenous contrast material. In this article, various experimental CT
      approaches for visualization and quantification of pulmonary perfusion are
      discussed. Ideally, CT will be able to provide both structural and functional
      information. Simple measurement of lung density before and after intravenous
      contrast delivery has been performed with single-slice CT technology using region
      of-interest methodology. For electron-beam CT, a repeated data acquisition on a
      7.6-cm lung volume has proven to be technically feasible. Using such dynamic
      scanning, reduced blood flow was observed in occluded lung segments. Color
      encoded parenchymal density distribution in the axial, coronal, and sagittal
      planes was derived from thin collimation data sets using four-row multi-slice
      spiral CT (MSCT). Initial animal data from 16-slice MSCT offer a real CT
      subtraction technique of the entire chest for the first time.

PMID- 15732563
TI  - Emergency preparedness, response & recovery checklist: beyond the emergency
      management plan.

PMID- 15732564
TI  - Year in review 2003-2004: overview.
AB  - The year preceding June 30, 2004, was one of the most active periods in the
      development of health policy and health law in a generation. Against the odds,
      President Bush delivered on his promise of a prescription drug benefit for
      Medicare beneficiaries. As with all momentous legislation, the prescription drug
      benefit was accompanied by legislative changes both large and small, affecting
      virtually every sector of the healthcare community. In addition to new
      legislation, the Bush administration continued to release regulations deemed
      vitally important by those regulated. The Joint Commission on Accreditation of
      Healthcare Organizations pursued new standards and processes to improve patient
      safety, and the courts dealt with a myriad of health law issues.

PMID- 15732565
TI  - "Medical necessity" determinations--a continuing healthcare policy problem.
AB  - To promote an understanding of the implications of current structures and
      processes for medical necessity determinations that affect everyone, directly or
      indirectly, the American Health Lawyers Association will devote its biannual
      Public Interest Colloquium (to be held in February 2005) to the topic. In
      preparation for the colloquium, the author summarizes the history and current
      importance of the topic, identifies stakeholders in the system and their
      interests, and sets forth a preliminary list of issues to be considered by the
      colloquium participants, focusing on potential elements of an ideal system for
      making medical necessity determinations.

PMID- 15732566
TI  - Ethical issues in international biomedical research: an overview.
AB  - Human subjects research has been the focus of numerous controversies over the
      years. The dilemma lies between the potential harm to individuals who participate
      in research and the knowledge to be gained from the research study that might
      benefit society. When research is conducted in developing countries by
      researchers and sponsors from the United States and other industrialized
      countries, differences in history, culture, politics, wealth, and power between
      the countries give rise to unique challenges. In this Article, the author
      identifies several ethical issues to be considered when research is conducted in
      developing countries and provides the legal and ethical framework for their
      resolution.

PMID- 15732567
TI  - Minors' rights to consent to treatment: navigating the complexity of State laws.
AB  - State laws recognize that a competent adult patient has the right to consent to
      or refuse medical treatment. While the law is clear with regard to the right of
      competent adults, state statutes are more complicated when the patient is a
      minor. While the law should, and does, attempt to balance the rights and
      obligations of parents and guardians against the access and privacy rights of
      minors, complicated state statutory schemes often fail to simultaneously address
      those contrasting goals in a consistent and uniform manner. The result is a
      confusing set of seemingly arbitrary and sometimes conflicting provisions that
      require the detailed attention of healthcare providers to ensure legal
      compliance. With the aim of helping healthcare practitioners meet their legal
      obligations, this Article examines state laws governing minor's consent rights
      byfocusing on the instances in which a minor's parent, guardian, or other
      authorized adult is permitted to consent to treatment on behalf of a minor and
      the instances in which a minor is authorized to act independent of adult
      intervention.

PMID- 15732568
TI  - Impaired practitioner policy.

PMID- 15732569
TI  - Professional development in the youth development field: issues, trends,
      opportunities, and challenges.
AB  - This chapter reviews key issues in professional development in the youth
      development field, describing important work done over the past two decades and
      lessons learned from major philanthropic investments in capacity building both
      nationally and locally.

PMID- 15732570
TI  - Getting down to business: defining competencies for entry-level youth workers.
AB  - In January 2004, the National Collaboration for Youth approved a list of core
      competencies needed by entry-level youth development workers for effective youth
      development practice. This chapter provides an overview of these competencies,
      explaining why and how the list was created, outcomes, and recommendations for
      next steps.

PMID- 15732571
TI  - Achieve Boston: a citywide innovation in professional development.
AB  - Achieve Boston is a broad-based collaborative effort to improve the overall
      quality of programs for children and youth by establishing a professional
      development infrastructure that supports those who work with young people during
      the out-of-school-time hours.

PMID- 15732572
TI  - The intermediary role in youth worker professional development: successes and
      challenges.
AB  - This chapter examines the role of a national network of local and regional
      intermediary organizations in initiating and sustaining community-based youth
      worker professional development systems. This approach is instructive for other
      intermediaries in establishing training standards, assessing impact, providing
      organizational supports for youth development workers, and going to scale.

PMID- 15732573
TI  - Professional development in national organizations: insights from Girls
      Incorporated.
AB  - The largest national youth organizations have targeted, comprehensive
      professional development systems. For one of them, Girls Incorporated, its
      mission "to inspire all girls to be strong, smart, and bold" drives
      sophisticated, evaluated professional development for affiliate staff and
      trustees.

PMID- 15732574
TI  - Professionalizing youth development: the role of higher education.
AB  - Certificates, credentials, and degrees offered through institutions of higher
      education allow youth development professionals to acquire educational
      experiences that are recognized in a formal manner.

PMID- 15732575
TI  - Reflections on the road not (yet) taken: how a centralized public strategy can
      help youth work focus on youth.
AB  - Karen Pittman calls for innovation and systemic change in the U.S. youth work by
      examining the key values of the United Kingdom's national youth work system.

PMID- 15732576
TI  - In vivo detoxification of Fusarium toxins.
AB  - Fusarium toxins are of great practical relevance in animal feeding since they may
      occur in toxicologically relevant concentrations. Therefore, many attempts have
      been made to find ways to detoxify contaminated feedstuffs or diets in order to
      cope with the problem. The supplementation of contaminated diets with detoxifying
      agents seems to be easily feasible, and in vitro results seem to be convincing.
      According to the Guideline 87/153/EEC of the Council of the European Communities,
      efficacy has to be proven by using an experimental design justified by the claims
      for use of the additive. In a review of the literature, only a few studies
      investigated specific parameters that could clearly reflect the claimed mode of
      action of the additives, and those demonstrated no measurable detoxifying
      effects. The majority of investigations focused on rather non-specific
      performance parameters, while many of these applied incomplete experimental
      designs. Nevertheless, most of the experiments did not demonstrate preventive
      effects. It is concluded that testing of currently available detoxifying agents
      did not follow the Council Directive in style and since the claim for their use
      was not proven. The application of complete two by two factorial experimental
      designs, the investigation of mycotoxins and/or metabolites in physiological
      samples as specific parameters and the verification of the specificity of the
      detoxifying agent is recommended for future in vivo investigations.

PMID- 15732577
TI  - Specific enumeration of the probiotic strain Enterococcus faecium NCIMB 10415 in
      the intestinal tract and in faeces of piglets and sows.
AB  - The intestinal bacterium Enterococcus faecium NCIMB 10415 (E. faecium SF68) has
      been used for more than a decade as a probiotic strain in animal nutrition as
      well as in the prevention and treatment of diarrhoea in humans. Beneficial
      effects have been shown in feeding and clinical trials. However, the strain has
      no selective growth markers and monitoring in the intestinal tract is impossible
      by cultivation. Using specific nucleotide sequences, in this study a probe for
      colony hybridization was constructed in order to quantify this probiotic strain
      in feed and intestinal and faecal samples from piglets and sows. The probiotic
      strain showed almost constant amounts in sow faeces (1.8 x 10(5) cfu/g wet
      weight), while contents in digesta and piglet faeces varied on a lower level
      depending on gut section and piglet age. The ratio of specific probiotic counts
      and total enterococci was much lower than in sow faeces however the strain could
      be detected reliably in faeces already on the 14th day of life. The application
      of the colony hybridization method enables for the first time the selective
      detection of the widely used probiotic E. faecium NCIMB 10415 strain among total
      Enterococcus spp. counts of digesta, faeces and feed. It is now possible to
      monitor the presence of the probiotic in the intestinal tract and faeces. Results
      of this study have implications for the proposed modes of action of probiotics in
      animal nutrition.

PMID- 15732578
TI  - Effect of a soy protein diet on protein and energy metabolism and organ
      development in protein-restricted growing pigs.
AB  - Two feeding experiments were carried out with castrated male pigs weighing
      between 10 and 30 kg to study acute and persisting dietary effects on growth and
      on protein and energy metabolism in growing pigs. Pigs were fed semi-synthetic
      isoenergetic and isonitrogenous diets at 50% protein requirement with either soy
      protein isolate (SPI) or casein (CAS) as sole protein source. Intake of protein
      and ME amounted to 9% w/w and 1800 kJ x kg BW (-0.62) x d(-1) in Exp. 1,
      respectively, and 9% w/w and 1430 kJ x kg BW(-0.62) x d(-1) in Exp. 2. The CAS
      diet was supplemented by Lys, Met, Thr and Trp. In Exp. 1 (acute effects), 18
      pigs received the CAS diet for 24 days (period 1); 9 pigs were then switched to a
      SPI diet whereas 9 pigs continued on the CAS diet for another 31 days (period 2).
      In Exp. 2, a third period of 31 days was added in which the SPI group was
      switched back to CAS diet. The control group was fed on the CAS diet throughout
      Exp. 2 (86 days). Altogether the majority of parameters were not affected neither
      comparing SPI with CAS in Exp. 1 nor inspecting possible persistence of effects
      in Exp. 2. In detail, in Exp. 1 SPI compared to CAS feeding resulted in a lower
      efficiency of protein utilisation and lower protein retention. Attendant upon the
      lower protein retention an increased energy retention as fat was only observed in
      tendency. SPI feeding caused a decreased body weight, thyroid weight and
      increased hepatic carbohydrate content that persisted after the diet was changed
      back to CAS (Exp. 2).

PMID- 15732579
TI  - The effect of genistein supplementation on performance and antioxidant status of
      Japanese quail under heat stress.
AB  - Genistein, a phytoestrogen found in soybeans, is a powerful antioxidant. We
      evaluated the effects of genistein supplementation on performance, carcass
      characteristics, levels of malondialdehyde (MDA), homocysteine, vitamins C, E, A
      in Japanese quail (Coturnix coturnix japonica) exposed to high ambient
      temperature of 34 degrees C. Two hundred and forty Japanese quails (10 d old)
      were randomly assigned to eight treatment groups consisting of 10 replicates of
      three birds. The birds were kept in an environmental controlled room either for
      24 h/d at 22 degrees C with (thermoneutral, TN groups) or for 16 h/d at 22
      degrees C and for 8 h/d (09.00 am to 05.00 pm) at 34 degrees C (heat stress, HS
      groups). Birds were fed either a basal (control) diet (TN and HS) or the basal
      diet supplemented with 200, 400 or 800 mg of genistein per kg of diet. Heat
      exposure decreased birds' performance when basal diet was fed. Increase in feed
      intake and body weight, and improvement of feed efficiency and carcass traits
      were found in genistein-supplemented quails reared under heat stress conditions.
      Growth rate and feed efficiency improved in quails reared under thermo-neutral
      conditions as well. Concentration of serum vitamins C, E, and A increased in
      supplemented birds reared at high temperature, while non-significant changes
      occurred in TN groups. With genistein supplementation homocysteine levels in
      serum and MDA levels in serum and liver decreased in all birds of both TN and HS
      groups. Effects of genistein were relatively greater in heat-stressed quails than
      in quails kept under thermo-neutral conditions. Results of the present study
      suggest that supplementation with genistein can be considered to be protective by
      reducing the negative effects of oxidative stress induced by heat stress in
      quail.

PMID- 15732580
TI  - Effects of dietary L-carnitine and coenzyme Q10 supplementation on performance
      and ascites mortality of broilers.
AB  - The study was conducted to determine the effects of dietary L-carnitine and
      coenzyme Q10 (CoQ10) supplementation on growth performance and ascites mortality
      of broilers. A 3 x 3 factorial arrangement was employed with three levels (0, 75
      and 150 mg/kg) of L-carnitine and three levels of CoQ10 (0, 20 and 40 mg/kg)
      supplementation during the experiment. Five hundred and forty one-day-old Arbor
      Acre male broiler chicks were randomly allocated into nine groups with six
      replicates each. All birds were fed with the basal diets from day 1 to 7 and
      changed to the experimental diets from day 8. During day 15 to 21 all the birds
      were exposed to low ambient temperature (15-18 degrees C) to induce ascites. The
      results showed that under this condition, growth performance of broilers were not
      significantly affected by CoQ10 or L-carnitine + CoQ10 supplementation during
      week 0-3 and 0-6, but body weight gain (BWG) of broilers was significantly
      reduced by 150 mg/ kg L-carnitine during week 0-6. Packed cell volume (PCV) of
      broilers was significantly decreased by L-carnitine and L-carnitine + CoQ10
      supplementation (P < 0.05). Erythrocyte osmotic fragility (EOF), ascites heart
      index (AHI) and ascites mortality of broilers were significantly decreased by L
      carnitine, CoQ10 and L-carnitine + CoQ10 supplementation. Though no significant
      changes were observed in total antioxidative capability (T-AOC), total superoxide
      dismutase (T-SOD) was increased by L-carnitine, CoQ10 and L-carnitine + CoQ10
      supplementation (P < 0.05). Malonaldehyde (MDA) content was significantly
      decreased by CoQ10 and L-carnitine + CoQ10 supplementation. The results indicate
      that dietary L-carnitine and CoQ10 supplementation reduce ascites mortality of
      broilers; the reason may be partially associated with their antioxidative
      effects.

PMID- 15732581
TI  - Gastrointestinal and immunological responses of senior dogs to chicory and mannan
      oligosaccharides.
AB  - Thirty-four senior dogs (pointers 8-11 years, beagles 9-11 years) were used to
      evaluate the effects of oligosaccharides on nutritional and immunological
      characteristics. Dogs were randomly allotted to treatments [1% chicory (CH), 1%
      mannan-oligosaccharide (MOS), 1% chicory + 1% MOS (CM), or no supplementation
      (control, CON)] in a parallel design with a 4 week baseline period followed by a
      4 week treatment period. Dietary supplementation with MOS or CM tended (P = 0.07)
      to increase food intake due, in part, to an increase in fermentable fibre and a
      decrease in energy content of the diet. Although wet faecal output increased (P <
      0.05) for dogs supplemented with MOS or CM, when corrected for food intake, no
      differences were noted. The CM treatment increased (P < 0.05) faecal score (1 =
      hard and dry, 5 = watery liquid), although these scores remained in a desirable
      range (3 to 3.5). Chicory supplementation increased (P = 0.07) fat digestibility.
      Chicory or MOS increased (P < or = 0.05) faecal bifidobacteria concentrations 0.4
      and 0.5 log10 cfu/g DM, respectively, compared to the CON, while MOS decreased (P
      < 0.05) faecal E. coli concentrations. Oligosaccharides did not affect white
      blood cell (WBC) concentrations, but CH and CM tended to increase (P = 0.10)
      neutrophil concentrations compared to control dogs. Peripheral lymphocyte
      concentrations were decreased in dogs supplemented with MOS (P = 0.06) and CM (P
      < 0.05). Chicory and MOS alter faecal microbial populations and certain indices
      of the immune system of senior dogs.

PMID- 15732582
TI  - Utilization of energy for growth in lambs of the breed German Merino Landsheep.
AB  - Based on energy deposition and energy intake the utilization of energy for fat
      and protein deposition and the mean energy utilization for growth as well as the
      energy requirement for maintenance were estimated in this study. Fifty-four male
      and 54 female lambs were fed at three feeding levels and slaughtered at various
      body weights (BW): 18, 30, 45, and 55 kg. Based on the method of the comparative
      slaughter technique the total body of each animal was analysed. From the data of
      empty-body gain, fat, protein and energy deposition in the different fattening
      periods was calculated. The utilization of metabolizable energy for growth and
      maintenance was estimated by a multiple linear regression model. In this
      regression model, a utilization of energy for fat deposition of 71% and for
      protein deposition of 30% was determined (R2 = 0.869). The requirement for
      maintenance was 520 kJ x kg BW(-0.75) x d(-1). A slightly higher requirement for
      maintenance was determined for female lambs. The study indicated that the used
      regression model can be recommended to estimate the utilization of energy and the
      requirement for maintenance in growing lambs.

PMID- 15732583
TI  - Effects of long-term storage on Fusarium toxin concentrations in wheat--sources
      of error of the analytical results.
AB  - The concentrations of the Fusarium toxins deoxynivalenol (DON) and zearalenone
      (ZON) of a heavily contaminated wheat grain batch were followed over a period of
      1 year by taking samples 15 times every 28 days. The air temperature and relative
      humidity at the top of the wheat batch ranged between 7 and 22 degrees C and 44
      and 55%, respectively, and corresponded to a variation in the moisture content of
      the wheat grain between 11.5 and 12.3%. None of these fluctuations were related
      to ZON and DON concentrations, which varied between 0.46 and 0.66 and 15.0 and
      19.5 mg/kg DM. Therefore, the data were used to analyse the error sources for the
      analytical results. It was found that the variance proportions due to sampling
      and sample preparation plus analysis were not similar for DON and ZON. The
      variance proportion due to sampling was found to be 0.62 for ZON, which
      corresponded to a variance proportion of 0.38 due to sample preparation plus
      analysis. In contrast, the latter variance proportion for DON was estimated to be
      1.0 and consequently completely superimposed the sampling error. It is concluded
      that long-term storage of contaminated wheat grain does not affect the
      concentrations of DON and ZON considering the measured fluctuations in ambient
      temperature, relative humidity and moisture content of the grain. Therefore, no
      degradation of DON and ZON occurred during the storage of wheat for a period of
      one year under ambient conditions. The effects of sampling and sample preparation
      plus analysis on the final analytical results are different for DON and ZON and
      require further consideration.

PMID- 15732584
TI  - Comparative studies of mitogen- and antigen-induced lymphocyte proliferation in
      four captive rhinoceros species.
AB  - Cellular immune function in four rhinoceros species was evaluated by way of in
      vitro lymphocyte proliferation responses to mitogenic and antigenic stimuli to
      establish normative data on white blood cell activity for each species and to
      identify species-specific differences that might help explain the predisposition
      of black rhinoceroses (Diceros bicornis) to disease. A cross section of the U.S.
      rhinoceros population encompassing all four captive species was sampled,
      including the Sumatran rhinoceros (Dicerorhinus sumatrensis) (n = 3); Indian
      rhinoceros (Rhinoceros unicornis) (n = 4); African black rhinoceros (n = 16); and
      African white rhinoceros (Ceratotherium simum) (n = 10). Of the four species
      evaluated, African black rhinoceroses exhibited the weakest (P < 0.05) lymphocyte
      proliferative responses to the mitogens: pokeweed (0.1 microg/ml),
      phytohemagglutinin (0.3 microg/ml), and concanavalin A (5.0 microg/ml). Total
      cell density at the end of culture was only 70% of that achieved with lymphocytes
      isolated from African white rhinoceroses, Indian rhinoceroses, and Sumatran
      rhinoceroses. However, lymphocyte response to bacterial endotoxin
      lipopolysaccharide was similar (P > 0.05) across species. Antigenic stimulation
      produced much weaker responses than mitogenic stimulation. No differences (P >
      0.05) were observed among rhinoceros species in response to 1 and 10 microg/ml of
      Leptospira icterohemorrhagiae or Leptospira gryppotyphosa. Lymphocytes from
      African white rhinoceroses proliferated weakly in the presence of Aspergillus
      fumigatus filtrate, whereas lymphocytes from the southern black rhinoceros
      subspecies appeared slightly suppressed in the presence of increasing doses (0.1,
      1, and 10 microg/ml) of Aspergillus filtrate. This comparative data set
      characterizing lymphocyte proliferation in the rhinoceros reveals several
      differences in immune cell responses among rhinoceros species and provides some
      evidence that lymphocytes of captive African black rhinoceroses are less vigorous
      than those of the other rhinoceros species.

PMID- 15732585
TI  - Semen collection and artificial insemination in the common piping guan (Pipile
      cumanensis cumanensis): potential applications for Cracidae (Aves: Galliformes).
AB  - The common piping guan (Pipile cumanensis cumanensis) is serving as a model for
      assisted reproductive techniques (ARTs) in Cracidae (Aves: Galliformes). Manual
      collection methods used in domestic birds and other exotics were modified to
      optimize quality and quantity of fresh semen samples. In addition, a method to
      subjectively assess semen quality on the basis of its color, clarity, and
      consistency was developed to serve as a tool when laboratory equipment is not
      available. In a species where only two eggs per clutch is typical, predictability
      of the date of the first egg is critical to ensure adequate inseminations before
      oviposition. An increase in both the distance between the female's pubic bones
      and degree of abdominal swelling indicated optimal time to initiate artificial
      insemination (AI) and allowed the number of semen samples used to fertilize the
      first egg in the clutch to be minimized while ensuring its fertility. In three
      separate AI trials, a total of four fertile eggs were produced, a first for
      cracids. Two of the four fertile eggs hatched successfully, and the chicks'
      parentages were confirmed using DNA fingerprinting. This study represents the
      first published account of the use of ARTs in Cracidae and forms the basis for
      future developments (e.g., AI of frozen-thawed semen) aimed at optimizing genetic
      management of cracids in ex situ breeding programs.

PMID- 15732586
TI  - Endoscopic sex determination and gonadal manipulation in Gulf of Mexico sturgeon
      (Acipenser oxyrinchus desotoi).
AB  - Seventeen Gulf of Mexico sturgeons (Acipenser oxyrinchus desotoi) underwent
      endoscopic sex determination, gonadal biopsy, and various reproductive surgeries
      as part of a conservation development plan. The fish were anesthetized with
      tricaine methanesulfonate (MS-222) buffered with sodium bicarbonate and
      maintained on a recirculating water anesthesia circuit. A 6-mm Ternamian EndoTip
      Cannula, placed through the ventral midline, midway between pectoral and pelvic
      fins, permitted the introduction of a 5-mm telescope. Swim bladder aspiration and
      CO2 insufflation of the coelomic cavity provided excellent observation. Second
      and third cannulae were placed under direct visual control, lateral and cranial
      or caudal to the telescope cannula. Sex determination was successfully performed
      in all fish; however, five of 17 sturgeons (29%) required endoscopic gonadal
      biopsy to confirm sex. Bilateral ovariectomy or orchidectomy was successfully
      performed in three males and four females. Unilateral ovariectomy and bilateral
      ligation of the mullerian ducts using an extracorporeal suturing technique was
      accomplished in an additional three females. No apparent morbidity was associated
      with the anesthesia or endoscopic surgery in any fish. The ability to safely
      perform minimally invasive reproductive surgery in fish may have important
      management and conservation benefits.

PMID- 15732587
TI  - Plasma biochemistry reference values of wild-caught southern stingrays (Dasyatis
      americana).
AB  - Stingrays are prominent marine animals; however, there are few published
      reference values for their blood chemistry and hematology. Twenty-eight southern
      stingrays (Dasyatis americana) were caught using the bottom trawl nets of fishery
      independent boats operated by the South Carolina Department of Natural Resources
      during June and July 2002 from Winyah Bay, South Carolina, to St. Augustine,
      Florida. Median values of blood and plasma obtained from live animals promptly
      after capture are as follows: packed cell volume = 0.22 L/L (22%), total solids
      (TS) = 56.5 g/L (5.65 g/dl), total protein (TP) = 26 g/L (2.6 g/dl), sodium = 315
      mmol/L, potassium = 4.95 mmol/L, chloride = 342 mmol/L, calcium = 4.12 mmol/L
      (16.5 mg/dl), phosphorus = 1.5 mmol/L (4.7 mg/dl), urea nitrogen = 444 mmol/L
      (1,243 mg/dl), glucose = 1.69 mmol/L (30 mg/dl), aspartate aminotransferase =
      14.5 U/L, creatine phosphokinase = 80.5 U/L, osmolality = 1065 mOsm/kg, and
      lactate = 3.1 mmol/L. Bicarbonate was less than the low end of the instrument
      range (5 mmol/L) in all but three samples. Anion gap was negative in all samples.
      Albumin was less than the low end of the instrument range (1 g/dl) in all except
      one sample. Osmolality was significantly higher in the rays caught in the
      southern region. TS and TP values were linearly related to each other, and the
      equation for the fitted line is TS = (11.61 x TP) + 25.4 (in g/L) [or TS = (1.161
      x TP) + 2.54 (in g/dl)]. The reference ranges reported in this study can be used
      to aid in the management of aquarium stingrays and to create a baseline for
      health monitoring of the wild Dasyatis spp.

PMID- 15732588
TI  - Pharmacokinetics of oxytetracycline in loggerhead sea turtles (Caretta caretta)
      after single intravenous and intramuscular injections.
AB  - The pharmacokinetics of oxytetracycline in 2-yr-old loggerhead sea turtles
      (Caretta caretta) after single i.v. and i.m. injections were studied for biologic
      marking and therapeutic applications. Twenty juvenile turtles were divided into
      two treatment groups. Ten animals received 25 mg/kg of oxytetracycline i.v. and
      10 received the same dosage i.m. Plasma oxytetracycline concentrations were
      analyzed by reverse-phase high-performance liquid chromatography. Data from the
      i.v. route best fit a three-compartment model, whereas noncompartmental analysis
      was used to compare data from both the i.v. and i.m routes. For the i.v. route,
      means for maximum plasma concentration, terminal phase half-life, systemic
      clearance, and apparent volume of distribution at steady state were 6.6
      microg/ml, 66.1 hr, 290.7 ml/hr/kg, and 18.4 L, respectively. For the i.m. route,
      means for systemic availability, maximum plasma concentration, and elimination
      half-life were 91.8%, 1.6 microg/ml, and 61.9 hr, respectively. The remarkably
      high apparent volume of distribution may possibly be associated with a deep
      compartment of drug disposition such as bone deposition associated with the large
      skeletal mass of turtles and the fact that these were well-nourished, growing
      juveniles. Although maximum plasma concentration by i.m. administration was lower
      than for the i.v. route, the long elimination time indicates that an infrequent
      dosing interval may be effective for sensitive bacteria.

PMID- 15732589
TI  - Pharmacokinetics of carfentanil and naltrexone in domestic goats (Capra hircus).
AB  - Using a crossover study design, the pharmacokinetics of carfentanil and
      naltrexone after i.v., i.m., and s.c. administration were determined in eight
      domestic goats (Capra hircus). Serial blood samples were taken up to 120 hr after
      carfentanil administration, and the plasma drug concentrations were determined
      using liquid chromatography and mass spectroscopy. All goats were immobilized
      with 40 microg/kg carfentanil i.m., although the resulting neurologic effects
      varied considerably. Plasma profiles showed rapid carfentanil absorption and a
      simple biphasic decline for 12-48 hr. Naltrexone given at 100 mg naltrexone/mg
      carfentanil 30 min after carfentanil administration produced rapid reversal of
      immobilization after all routes of administration. Variable fluctuations in the
      naltrexone plasma concentrations during the first 2.5-3.5 hr were observed,
      followed by a more consistent biphasic decline. The time to standing was
      significantly shorter after i.v. compared with s.c. naltrexone, although the time
      difference (1 min) had little clinical relevance. No statistically significant
      differences between the naltrexone pharmacokinetic parameters measured for the
      three routes of naltrexone administration were identified, although the
      recoveries after i.m. administration were, subjectively, the smoothest. The
      carfentanil half-life did not differ significantly in the goats given naltrexone
      by different routes. Although it is currently recommended that the naltrexone
      dose be divided into s.c. and i.v. portions, this practice does not appear to
      offer any benefit.

PMID- 15732590
TI  - Four preanesthetic oral sedation protocols for rhesus macaques (Macaca mulatta).
AB  - The efficacies and ease of administration of four oral preanesthetic sedation
      protocols were compared in 18 adult, male rhesus macaques (Macaca mulatta) to
      achieve heavy sedation and alleviate anxiety, agitation, and potential trauma
      associated with remote anesthesia induction. The macaques, with average age and
      weight of 10 yr and 12.5 kg, respectively, were randomly assigned to one of four
      groups. Group 1 was given 10 mg/kg tiletaminezolazepam and 0.05 mg/kg
      medetomidine p.o., group 2 was given 1 mg/kg midazolam and 20 mg/kg ketamine
      p.o., group 3 was given 20 mg/kg ketamine and 0.05 mg/kg medetomidine p.o., and
      group 4 was given 3 mg/kg midazolam p.o. All protocols produced effects ranging
      from mild sedation to no response to noxious stimuli, depending on the success of
      administration. The mean interval to peak effect was 27-43 min in all groups.
      Ketamine and medetomidine provided significantly better sedation than midazolam
      alone; there were no other statistically significant differences among the four
      protocols. Oral tiletamine-zolazepam and medetomidine provided smooth, mild to
      moderate sedation with few side effects. The midazolam and ketamine combination
      resulted in severe ataxia. Orally administered ketamine and medetomidine provided
      smooth, easily reversible, heavy sedation leading to no response to noxious
      stimuli. Midazolam alone provided only mild sedation. No statistically
      significant differences in palatability of the four protocols were identified.
      Orally administered ketamine and medetomidine (group 3) provided the most
      consistently heavy sedation. A compounding pharmacy may be able to increase the
      palatability and level of acceptance of these combinations. Alternatively, oral
      midazolam syrup is well accepted by some animals and provides a mild sedative and
      calming effect, which may decrease stress associated with the induction of
      anesthesia via darting, pole syringes, etc.

PMID- 15732591
TI  - Molecular and serologic evidence of tick-borne Ehrlichiae in three species of
      lemurs from St. Catherines Island, Georgia, USA.
AB  - In recent years, several species of ehrlichiae have been recognized as tick-borne
      disease agents of veterinary and medical importance. Clinically normal free
      ranging or previously free-ranging lemurs, including 46 ring-tailed lemurs (Lemur
      catta), six blue-eyed black lemurs (Eulemur macaco flavifrons), and four black
      and white ruffed lemurs (Varecia variegata variegata) from St. Catherines Island,
      Georgia, were tested for evidence of exposure to tick-borne ehrlichiae. All 52
      adult lemurs were serologically tested for exposure to Ehrlichia chaffeensis and
      Anaplasma phagocytophilum. Polymerase chain reaction (PCR) assays for E.
      chaffeensis, A. phagocytophilum, Ehrlichia ewingii, and Ehrlichia canis were
      conducted on blood samples from all 56 lemurs. Blood from all lemurs was
      inoculated into DH82 cell cultures for E. chaffeensis isolation. Of the adult
      lemurs, 20 (38.5%) and 16 (30.8%) had antibodies reactive (> or =1:128) for E.
      chaffeensis and A. phagocytophilum, respectively. Two ring-tailed lemurs were PCR
      and culture positive for E. chaffeensis. Molecular characterization of the two E.
      chaffeensis isolates showed that both contained 5-repeat variants of the variable
      length PCR target (VLPT) antigen gene and 3-repeat variants of the 120-kDa
      antigen gene. Sequencing of the VLPT genes revealed a novel amino acid repeat
      unit (type-9). One lemur infected with E. chaffeensis was slightly
      hypoproteinemic and had moderately elevated serum alanine aminotransferase (ALT)
      levels. These lemurs from St. Catherines Island have been exposed to or infected
      with tick-borne ehrlichiae, or both, but showed no clinical disease.

PMID- 15732592
TI  - Electrocardiography of rock partridges (Alectoris graeca) and chukar partridges
      (Alectoris chukar).
AB  - Standard limb, six lead (I, II, III, aVR, aVL, and aVF) electrocardiograms (ECGs)
      were recorded in 10 awake mature rock partridges (Alectoris graeca) and 10 chukar
      partridges (Alectoris chukar). Durations and amplitudes of P and T waves and QRS
      complexes, durations of P-Q and Q-T intervals, and mean heart rates were
      calculated from the lead II ECGs. All observable P and T waves were negative in
      aVR and aVL, whereas they were positive in all remaining leads. The most frequent
      forms of QRS complex were r-s (r-S) and q-r (q-R). A Q wave was observed in all
      aVR and aVL leads in both species. Chukar partridges had significantly higher
      amplitudes of P and T waves and QRS complexes than rock partridges. Mean heart
      rates were 310+/-15 beats/min and 317+/-19 beats/min for chukar partridges and
      rock partridges, respectively. Mean electrical axes, calculated from leads II and
      III, were -99+/-6.3 degrees and -95+/-1.7 degrees for chukar partridges and rock
      partridges, respectively. Clear ECGs were easily obtainable without anesthesia or
      sedation.

PMID- 15732593
TI  - Effects of surgical implantation of temperature dataloggers on reproduction of
      captive striped skunks (Mephitis mephitis).
AB  - A total of 20 (14 females, six males) captive striped skunks (Mephitis mephitis)
      with miniature temperature dataloggers implanted free in the abdominal cavity
      were examined for reproductive performance and pathology because of implants.
      Eleven of 12 female skunks reproduced successfully 45.9+/-3.7 days after surgery
      to remove implanted dataloggers. The pregnancy rate of 91.7% (11/12) was much
      higher than other captive studies and was comparable with that of wild skunks.
      Eight striped skunks (six males, two females) that were euthanatized and
      necropsied after having implants in the abdominal cavity for 5 mo showed no
      apparent pathology associated with the implant. Implantation of the
      intraperitoneal devices did not lead to complications in abdominal tissues.
      Neither implant nor surgery affected reproduction. We conclude that implanted
      dataloggers can safely be used in physiologic studies of striped skunks or
      possibly other small carnivores in captive or field studies.

PMID- 15732594
TI  - Cataract surgery with foldable intraocular lens implants in captive lowland
      gorillas (Gorilla gorilla gorilla).
AB  - Two juvenile, male, captive-born lowland gorillas (Gorilla gorilla gorilla) with
      the same father but different mothers developed bilateral cataracts. The
      cataracts were surgically removed within 6 yr and 3 mo, respectively, of
      diagnosis, and foldable intraocular lenses were implanted. Although vision was
      not restored in one eye with a mature, 6-yr-old cataract in gorilla A, surgical
      intervention on the other eye was performed before a complete cataract developed,
      and vision was fully restored. Gorilla B was treated at the age of 17 mo, and
      normal visual development proceeded in both eyes. This animal developed bilateral
      after-cataract and therefore needed a second intervention in both eyes using
      Nd:YAG laser treatment. The genetic component of juvenile cataracts should be
      considered in breeding management programs.

PMID- 15732595
TI  - Ventricular phytobezoar impaction in three micronesian kingfishers (Halcyon
      cinnamomina cinnamomina).
AB  - Three juvenile male Micronesian kingfishers (Halcyon cinnamomina cinnamomina)
      housed in the same enclosure presented with rapid weight gain and coelomic
      distension. Physical examination and radiography revealed marked enlargement of
      the ventriculus and a single, large foreign body within the ventriculus in each
      individual. Surgical removal by ventriculotomy was attempted in one individual,
      which died during the procedure. A second individual was treated with natural
      peanut butter 0.5 ml p.o. b.i.d. for 14 days and recovered, casting the foreign
      material. The third bird was similarly treated without success and subsequently
      died during attempts at endoscopic removal of the foreign body. In all three
      birds, the foreign bodies proved to be phytobezoars. The birds had been observed
      stripping leaf fragments from live corn plants (Dracaena fragrans) used in the
      enclosure. Plant fibers from the phytobezoars were compared with D. fragrans
      leaves and were considered identical. Medical treatment of phytobezoars with
      peanut butter or similar oil-containing substances in birds should be considered
      as an alternative to surgical extraction.

PMID- 15732596
TI  - Toxoplasmosis in nilgais (Boselaphus tragocamelus) and a saiga antelope (Saiga
      tatarica).
AB  - Three captive female nilgais (Boselaphus tragocamelus) either showed late-term
      abortion or their newborn calves died within 2 days of birth. Toxoplasma gondii
      DNA was demonstrated in the brain and liver of each fetus and in one of the two
      neonates by single-stage polymerase chain reaction (PCR) with TGR1E and by
      seminested PCR with B1 gene. Retrospectively, antibodies titers > or =640 to T.
      gondii by indirect fluorescence were found in the sera of all three female and
      one male nilgais. No other cause of abortion was detected. Fatal toxoplasmosis
      was also diagnosed in one captive, adult female saiga antelope (Saiga tatarica),
      which died suddenly. Toxoplasma gondii was detected in the liver, lung, spleen,
      kidney, and intestine. An unusual finding was the presence of numerous tissue
      cysts in the liver of this animal. Toxoplasmosis was confirmed by PCR with TGR1E
      and immunohistochemically. Toxoplasmic hepatitis and pneumonia were considered to
      be the primary causes of death.

PMID- 15732598
TI  - Chemical immobilization of captive aardvark (Orycteropus afer).
AB  - Four aardvarks (Orycteropus afer) were anesthetized over a 6-yr period. They were
      sedated using detomidine (0.13+/-0.025 mg/kg i.m.; 0.12-0.14 mg/kg) and
      anesthetized with detomidine (0.12+/-0.025 mg/kg i.m.; 0.09-0.18 mg/kg) followed
      by ketamine (6.3+/-1.68 mg/kg i.m.; 4.3-8.2 mg/kg). Effects of anesthesia were
      reversed by atipamezole (0.065+/-0.013 mg/kg i.m.; 0.05-0.09 mg/kg). The
      detomidine-ketamine combination produced smooth anesthesia, excellent muscle
      relaxation, and was suitable for routine diagnostic and therapeutic interventions
      (blood collection, radiologic examinations, minor surgery).

PMID- 15732597
TI  - Ranavirus-associated morbidity and mortality in a group of captive eastern box
      turtles (Terrapene carolina carolina).
AB  - Seven captive eastern box turtles (Terrapene carolina carolina) from a large
      collection of North American chelonians in North Carolina became acutely ill in
      the fall of 2002. Five of the turtles died. Clinical signs included cutaneous
      abscessation, oral ulceration or abscessation (or both), respiratory distress,
      anorexia, and lethargy. The predominant postmortem lesion was fibrinoid
      vasculitis of various organs, including skin, mucous membranes, lungs, and liver.
      No inclusion bodies were detected by histopathology or electron microscopy of
      formalin-fixed tissue. An iridovirus was isolated from tissues obtained
      postmortem from two of the box turtles that died. The virus was characterized by
      electron microscopy, polymerase chain reaction, and sequence analysis of a
      portion of the major capsid protein as a member of the genus Ranavirus.

PMID- 15732599
TI  - Ebstein anomaly in a meerkat (Suricata suricatta).
AB  - An 8-yr-old male meerkat (Suricata suricatta) presented with sudden lethargy. A
      globular-shaped heart associated with pleural effusion on chest thoracic
      radiographs was consistent with congestive heart failure, and echocardiography
      was performed under general anesthesia. It revealed an Ebstein anomaly, with mild
      pericardial effusion and marked right heart enlargement. The animal was treated
      with imidapril chlorydrate. After 4 mo of treatment, thoracic radiographs still
      showed right-sided cardiomegaly; however, the animal appeared clinically normal.

PMID- 15732600
TI  - Proliferative enteritis associated with Lawsonia intracellularis in a Japanese
      macaque (Macaca fuscata).
AB  - A 2.5-yr-old, intact male Japanese macaque (Macaca fuscata) was observed to have
      a thickened ileum during exploratory laparotomy. Lawsonia intracellularis
      associated proliferative enteritis was diagnosed using histopathology (Warthin
      Starry stain), immunohistochemistry, and polymerase chain reaction analysis of
      the ileal biopsy. The animal developed transient diarrhea and severe
      hypoproteinemia 16 days after surgery but recovered with intensive treatment
      using azithromycin. Given the fact that very specific tests are required for
      identifying this organism, L. intracellularis may be underdiagnosed in nonhuman
      primates.

PMID- 15732601
TI  - Dermatophilus chelonae in a king cobra (Ophiophagus hannah).
AB  - A mass was removed from the left flank of a 10-yr-old male king cobra
      (Ophiophagus hannah), and histologic examination revealed granulomatous
      dermatitis with intralesional gram-positive cocci and filamentous bacteria.
      Fourteen months later, a histologically similar subcutaneous mass was removed
      from a different site. One year later, a large subcutaneous mass at the first
      surgical site was removed, and histopathologic examination revealed
      multiloculated granulomas with intralesional gram-positive cocci. An organism was
      cultured and identified by 16S ribosomal RNA gene sequencing as Dermatophilus
      chelonae. After a course of antibiotic therapy, no further lesions were seen for
      5 mo.

PMID- 15732602
TI  - Cutaneous and pulmonary mycosis in green anacondas (Euncectes murinus).
AB  - Two dead, captive green anacondas (Eunectes murinus), including one male and one
      female, submitted for necropsy were in poor body condition, having multiple,
      scattered, dark red foci on the scales and mottled lungs. Both snakes had severe
      mycotic dermatitis. In addition, the male snake had mycotic stomatitis, and the
      female snake had mycotic pneumonia. Trichophyton sp., Verticillium sp., and
      Alternaria sp. were isolated from the dermal lesions. The pulmonary lesions were
      morphologically consistent with Aspergillus sp. Bacterial organisms isolated from
      skin and internal organs included Chryseobacterium meningosepticum,
      Stenotrophomonas maltophilia, Aeromonas hydrophila, and Providencia rettgeri.
      Mycotic diseases can be devastating to reptiles, and suboptimal husbandry and
      captivity were likely the predisposing factors that led to opportunistic invasion
      in these snakes.

PMID- 15732603
TI  - Absence of detectable Salmonella cloacal shedding in free-living reptiles on
      admission to the wildlife center of Virginia.
AB  - Salmonellosis is an important reptile-associated zoonotic infection in the United
      States. Cloacal swabs were collected from reptiles admitted to the Wildlife
      Center of Virginia, Waynesboro, Virginia, cultured for Salmonella using Hektoen
      and xylose lysine deoxycholate agars, and inoculated in selenite broth. All three
      were incubated at 37 degrees C for 18-24 hr. Seventy-five animals were included
      in the study, representing eight species, 34 eastern box turtles (Terrapene
      carolina carolina), 14 eastern painted turtles (Chrysemys picta picta), 14
      snapping turtles (Chelydra serpentina), 6 black rat snakes (Elaphe obsoleta
      obsoleta), 2 redbelly turtles (Pseudemys rubriventris), 2 yellowbelly sliders
      (Trachemys scripta scripta), 2 eastern garter snakes (Thamnophis sirtalis
      sirtalis), and 1 eastern river cooter (Pseudemys concinna concinna). All cultures
      were negative for Salmonella spp., which is in contrast to the high prevalence of
      Salmonella cloacal shedding reported in captive reptiles but similar to previous
      reports in free-living North American reptiles. We recommend, nonetheless,
      practicing proper hygiene methods when handling and housing all reptiles.

PMID- 15732604
TI  - Pythiosis in a dromedary camel (Camelus dromedarius).
AB  - A 4.5-yr-old male dromedary camel (Camelus dromedarius) was evaluated for a mass
      on the right side of the face. A complete blood count and blood chemistry
      revealed anemia and hypoproteinemia. Radiographs did not reveal bony involvement.
      The mass was resected and Pythium insidiosum was cultured. The camel was treated
      with an experimental immunotherapeutic vaccine and with sodium iodide and
      ceftiofur. The camel began to lose weight postoperatively and died 6 mo later. At
      necropsy, the camel was found to have gastritis of the third compartment of the
      stomach with intralesional hyphae of this oomycete pathogen.

PMID- 15732605
TI  - Hip luxation in a woodchuck (Marmota monax): successful treatment by closed
      reduction and a modified Ehmer sling.
AB  - An elastic tape sling successfully maintained reduction of a craniodorsal right
      coxofemoral luxation in a woodchuck (Marmota monax). No complications were
      encountered during the 14 days that the sling was in place. The animal remained
      normal through the following 8 mo.

PMID- 15732606
TI  - Primary lymphangiectasia in a dingo (Canis familiaris dingo).
AB  - A 3-yr-old intact male dingo (Canis familiaris dingo) presented with a 3-mo
      history of diarrhea. The diarrhea did not resolve with antibiotics or intestinal
      protectants. Fecal examination for parasites, fecal cultures, physical
      examination, and radiographs were unremarkable. Enteroscopic duodenal biopsies
      showed dilated lacteals without inflammation. Results of serum folate, cobalamin,
      and trypsin-like immunoreactivity were normal. Low serum total protein and
      albumin combined with increased fecal levels of alpha-1 protease inhibitor
      suggested the diagnosis of lymphangiectasia. Full-thickness intestinal biopsies
      of the duodenum, jejunum, and ileum revealed dilated mucosal and submucosal
      lacteals without associated inflammation, confirming the diagnosis of primary
      lymphangiectasia. Currently, the dingo is being maintained with nutritional
      management.

PMID- 15732607
TI  - Coexisting tricuspid valve dysplasia and ventricular septal defect in a young
      patas monkey (Erythrocebus patas).
AB  - A 1.5-kg, 6-mo-old male patas monkey (Erythrocebus patas) was cyanotic and
      panting. Evaluation of the heart by electrocardiography, thoracic radiography,
      two-dimensional echocardiography, and Doppler color-flow echocardiography
      revealed a ventricular septal defect (VSD) with right-to-left shunting as well as
      tricuspid valve dysplasia with dilated annulus of the tricuspid ring, dilated
      right atrium, dilated right ventricle, and deformity of the tricuspid valve.
      Because of the severity of the cardiac disease, the patas monkey had
      complications recovering from anesthesia and died 3 days later. Gross postmortem
      findings included VSD, tricuspid dysplasia, and cerebral hemorrhage.

PMID- 15732608
TI  - Clinical challenge. Mural thrombus and external iliac arterial thromboemboli
      resulting from cardiomyopathy.

PMID- 15732609
TI  - Report of the fpaNI judicial review.

PMID- 15732610
TI  - Discrimination and prejudice: Muslim women's experiences of maternity care.

PMID- 15732611
TI  - There's something about Mary.

PMID- 15732612
TI  - Maternity units to the rescue.

PMID- 15732613
TI  - Living with live TV.

PMID- 15732614
TI  - Screening for major haemoglobinopathies.

PMID- 15732615
TI  - Is preceptorship valuable?
AB  - Preceptorship programmes for newly-qualified practitioners have been advocated by
      the UKCC (1999), therefore a preceptorship programme for midwives was introduced
      in Oxfordshire in 2000. The programme consisted of a three-month placement in a
      delivery suite (DS) and a three-month placement in an antenatal/postnatal ward
      environment. In 2001, it was decided to offer newly-registered midwives the
      opportunity to work in a community setting, rotating between DS and community on
      a fortnightly basis. To ascertain whether a community placement in a
      preceptorship programme provided the right balance between consolidation of
      skills and confidence, a research project was undertaken. This took the form of
      semi-structured interviews carried out before and after the completion of the
      amended programme. The project was conducted over a one-year period by the
      midwifery practice development team. A professional transcriber interpreted the
      interviews and the data was analysed by an independent reviewer. The research
      sample consisted of ten newly-qualified midwives and four preceptors. Findings
      identified that midwives valued and desired a period of initial support to
      consolidate their skills and knowledge, which helped to increase their confidence
      in their abilities regardless of the placement setting. Interestingly, midwives
      who had opted for a community placement continued to view childbirth as a normal
      life event, whereas hospital-based preceptees found their philosophy of care had
      changed at the end of the six-month programme. However, the midwives who had
      opted for a community placement found the fortnightly rotation too fragmented.
      The preceptorship programme also had a positive influence on retention rates,
      which may have been as a result of the midwives feeling more supported. In
      response to the findings of this research project, it was concluded that the
      community placement needed to be altered to a three-month placement, but should
      still be available to newly-qualified midwives as a placement option.

PMID- 15732616
TI  - A birth vision.

PMID- 15732617
TI  - Education and training of the maternity care assistant: developments from a BTEC
      diploma in maternity care.

PMID- 15732618
TI  - What do midwifery healthcare assistants do? Investigating the role of the trained
      healthcare assistant.
AB  - There has been relatively little discussion in the literature regarding the role
      of the healthcare assistant (HCA) in midwifery. The study examines and contrasts
      HCA duties in one maternity department in the Republic of Ireland. Observations
      of six trained HCAs were undertaken to evaluate if they have the relevant
      repertoire of skills as taught in a national training programme, and to assess if
      they are using these skills competently. Findings indicate that HCAs carried out
      more indirect patient care activities than direct care activities. Findings show
      that the HCA provided support to qualified staff by assisting them in a range of
      care activities. This was consistent with the specified job description and with
      their training programme. This exploratory study helps to further understand the
      role of the HCA. It identifies the activities that HCAs undertake in support of
      qualified staff in maternity settings. The findings highlight the need for
      further investigation to determine the relationship between the role of the
      trained HCA and the qualified midwife.

PMID- 15732619
TI  - Management of iron deficiency in pregnancy.
AB  - This article reviews a study, published in Clinical and Laboratory Haematology
      (2003), which looked at using iron-rich spa water (Spatone) as a prophylaxis
      against iron deficiency in pregnancy. Anaemia is a significant problem in
      pregnant women that can have a detrimental effect on the baby and mother. The
      problems of non-compliance with oral iron supplements in this population are well
      documented. This was a prospective, randomised, double-blind, placebo-controlled
      trial, and 102 patients were recruited into the study. Inclusion criteria
      included singleton pregnancy, booking haemoglobin >10.4g/dl and gestational age
      confirmed by ultrasound at 20 weeks. Primary outcome measures were compliance
      with treatments during the trial period, ferritin levels at 22 and 28 weeks and
      dyspepsia scores at 22 and 26 weeks. RESULTS: Mean ferritin levels fell by 24% in
      the Spatone group compared with a mean fall of 51% in ferritin levels in the
      control group, p = 0.016. In the Spatone group, 31% of patients raised their
      ferritin levels during the trial period compared with 11% in the control group.
      The authors concluded that Spatone is effective in maintaining iron stores in non
      anaemic patients and is well-tolerated. The study delivers a clear message to
      midwives--namely that Spatone has a place in the management of iron-deficient
      pregnant women, because it is well-tolerated and provides iron in a highly
      bioavailable form.

PMID- 15732620
TI  - Midwifery: Geburtshaus-style.

PMID- 15732621
TI  - Midwifery practice: a wider agenda.

PMID- 15732622
TI  - Caseload practice for Sure Start.

PMID- 15732623
TI  - . . . and then there was one.

PMID- 15732624
TI  - Appropriate eye care in the tsunami relief effort.

PMID- 15732625
TI  - Ergonomics and the optometrist.

PMID- 15732626
TI  - Optical coherence tomography: its clinical use for the diagnosis, pathogenesis,
      and management of macular conditions.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a noninvasive, noncontact
      transpupillary imaging technology that can image retinal structures in vive with
      a resolution of up to 10 microns. Anatomic layers within the retina can be
      differentiated and retinal thickness measured. The objective is to demonstrate
      clinical viability and useful interpretation of macular images derived from a
      commercially available OCT instrument. METHODS: A Stratus OCT (Zeiss-Humphrey,
      Dublin, California) imaging system was used to evaluate several pathological
      presentations of the macula in selected patients. Conditions illustrated in this
      case series were macular holes, epiretinal membranes, macular edema, idiopathic
      central serous choroidopathy, detachments of pigment epithelium and sensory
      retina, choroidal neovascular membranes, and retinal vascular occlusions.
      CONCLUSIONS: Acquired OCT images achieved structural information regarding
      anatomical characteristics of the conditions scanned. A cross-sectional
      resolution of 10 microns was accomplished, which is 10 times greater than current
      ultrasound. OCT provides important information that may be critical in the
      diagnosis and management of some ocular conditions. Its high-resolution scans may
      contribute to the better understanding of disease pathogenesis, as well as
      assistance in or confirmation of a diagnosis. This imaging technology provides
      important information beyond what can be seen on clinical examination, and offers
      a useful adjunct to other diagnostic imaging tools such as fundus photography,
      fluorescein angiography, and indocyanine green angiography.

PMID- 15732627
TI  - An analysis of high myopia in a pediatric population less than 10 years of age.
AB  - PURPOSE: The purpose of this article is to document a comprehensive clinical
      profile-including the prevalence of amblyopia, strabismus, and anisometropia-of a
      pediatric population less than 10 years of age who manifested 6.00 diopters or
      more of myopia. METHOD: A retrospective record review was performed on all
      pediatric patients less than 10 years of age, examined at the State University of
      New York (SUNY) State College of Optometry between 1998 and 2001, and with a
      spherical equivalent of 6.00 diopters or more of myopia. RESULTS: One hundred
      seventy-eight patients met the criteria. Amblyopia or reduced corrected visual
      acuity was present in 75.8% of the patients. Strabismus was present in 31.5% of
      the patients, with essentially equal numbers of esotropes and exotropes.
      Anisometropia was present in 35.4% of the patients. One hundred forty-five
      patients had high myopia in the absence of significant ocular or systemic
      compromising conditions. In this sample of 145, strabismus or anisometropia was
      an etiology for amblyopia. There was a greater prevalence of bilateral high
      myopia (64.8%) than unilateral high myopia. Anisometropia was present in 10.6% of
      the bilateral high myopes, and 78.4% of the unilateral high myopes. CONCLUSION:
      Children less than 10 years of age with high myopia have a high risk of having
      amblyopia, strabismus, and anisometropia.

PMID- 15732628
TI  - Enhance postoperative filtering bleb-induced vision difficulties with well-fitted
      GP contact (oxygen-permeable) lenses.
AB  - BACKGROUND: Occasionally contact lenses need to be fit on patients with filtering
      blebs. Gas-permeable (GP) lens fitting is still controversial because, although
      the contact lens can improve visual acuity and satisfy a patient's visual need,
      it can also compromise the bleb and increase the risk of ocular infection.
      METHODS: A retrospective review of charts evaluated patients wearing a GP contact
      lens a minimum of two months after trabeculectomy surgery. Seven optometrists and
      one ophthalmologist submitted data on 20 eyes (15 subjects). Success of the
      contact lenses on these eyes was evaluated, as well as patient history and ocular
      complications from the contact lens. Contact lens success was based on the
      patient's ability to wear a GP contact lens a minimum of 6 hours a day, at least
      4 days a week, without permanent damage or significant compromise to the bleb.
      RESULTS: GP contact lenses were successfully fit and worn on 17 of 20 eyes with a
      functioning filtering bleb (85%). Two of the 17 eyes terminated GP contact lens
      use after a few years for reasons unrelated to contact lens wear. Three eyes
      (15%) were unsuccessful and discontinued GP contact lens wear. Of the three eyes
      that were not successful in wearing a GP contact lens, two eyes discontinued wear
      secondary to contact lens intolerance and one eye discontinued contact lens wear
      as a result of fitting difficulties. There were no complications of blebitis or
      endophthalmitis, but two eyes were treated for bleb laceration and staining of
      the bleb. CONCLUSION: GP contact lenses can be successfully worn in eyes with
      filtering blebs. However, to reduce the risk of complication and infection,
      proper fitting guidelines should be followed and patients should return for
      evaluations at intervals of 6 months or less.

PMID- 15732629
TI  - Integrading infants into the care practice.

PMID- 15732630
TI  - Administrative safeguards required under the HIPAA security rule.

PMID- 15732631
TI  - 'Welcome to Medicare' examinations.

PMID- 15732632
TI  - Migraine article maligned cluster sufferers.

PMID- 15732633
TI  - Proactive approach works with contractors.

PMID- 15732635
TI  - Lifeguard on duty. This Space Age personal monitoring device locates workers in
      distress.

PMID- 15732634
TI  - Heading off harassment. Effective training is critical to limiting legal exposure
      for workplace harassment.

PMID- 15732636
TI  - High-level safety persuasion: influencing up, down, and sideways.

PMID- 15732637
TI  - High tech at low cost.

PMID- 15732638
TI  - Risks of involvement in contractor safety.

PMID- 15732639
TI  - New rules for HazMat transport.

PMID- 15732640
TI  - The art of meaningful recognition.

PMID- 15732641
TI  - It's all about communication.

PMID- 15732642
TI  - Key measures for successful improvements.

PMID- 15732643
TI  - The three changing faces of the U.S. workforce.

PMID- 15732644
TI  - On the cutting edge of safety.

PMID- 15732645
TI  - Be ready for emergencies.

PMID- 15732646
TI  - Successful dust capture.

PMID- 15732647
TI  - A new reality for mold professionals.

PMID- 15732648
TI  - Characteristics of effective online learning.

PMID- 15732649
TI  - When does quality count?: Perceptions of hearsay testimony about child sexual
      abuse interviews.
AB  - This study assessed how the quality of a sexual abuse investigative interview
      with a child and the age of the child influence jurors' reactions to either the
      original interview with the child or to testimony by an adult hearsay witness
      (the interviewer). Participants (N = 360) were randomly assigned to 1 of 12
      conditions in a 2 (type of testimony: hearsay testimony vs. child interview) x 3
      (interview quality: poor, typical, or good) x 2 (age of the child: 4 years old
      vs. 10 years old) factorial design. Participants reached individual verdicts,
      answered a series of questions, and then deliberated in a group with five other
      participants. As predicted, jurors in the child interview conditions were more
      likely to find the defendant guilty if they read the good interview than if they
      read either the poor or the typical interview, but in the hearsay conditions
      verdicts did not significantly differ by interview quality. These findings
      suggest that there is a significant loss of information when the testimony of a
      hearsay witness is used in place of the actual interview with the child, and call
      into question the appropriateness of admitting hearsay testimony by interviewers.

PMID- 15732650
TI  - Venirepersons's attitudes toward the insanity defense: developing, refining, and
      validating a scale.
AB  - Given the prevalence and predictive strength of negative attitudes toward the
      insanity defense, we conducted three studies with 426 venirepersons to develop an
      understanding and a measure of public attitudes toward the insanity defense. In
      these studies, we developed, iteratively refined, and cross-validated the
      insanity defense attitude-revised (IDA-R) scale. The results suggest that IDAs
      are underpinned by one's degree of (a) orientation toward strict liability, and
      (b) concern about perceived injustice and danger associated with the defense. The
      IDA-R assesses these two-dimensions with good internal consistency, convergent
      and divergent validity, and predictive utility. The IDA-R's predictive utility
      generalizes across jurisdictions and manipulation of case facts. Theoretical and
      practical implications for research and for identifying impartial jurors at voir
      dire are discussed.

PMID- 15732651
TI  - Crime victims serving as jurors: is there bias present?
AB  - This project examined the decisions of 2435 mock jurors of whom 984 reported
      being a victim of some type of crime and 982 reported knowing a close friend or
      relative who had been a victim. Participants watched a videotape of a trial of a
      burglary of a habitation and were asked to give individual verdicts. Results
      indicated that jurors who identified themselves as victims of the same crime
      convicted significantly more frequently than those who had not been victims.
      Victims of violent crimes (a type of crime dissimilar to that for which the
      defendant was on trial) were not more likely to convict than were non-victims.
      Implications of this research are discussed.

PMID- 15732652
TI  - "Intuitive" lie detection of children's deception by law enforcement officials
      and university students.
AB  - Adults' ability to detect children's deception was examined. Police officers,
      customs officers, and university students attempted to differentiate between
      children who lied or told the truth about a transgression. When children were
      simply questioned about the event (Experiment 1), the adult groups could not
      distinguish between lie-tellers and truth-tellers. However, participants were
      more accurate when the children had participated in moral reasoning tasks
      (Experiment 2) or promised to tell the truth (Experiment 3) before being
      interviewed. Additional exposure to the children did not affect accuracy
      (Experiment 4). Customs officers were more certain about their judgments than
      other groups, but no more accurate. Overall, adults have a limited ability to
      identify children's deception, regardless of their experience with lie detection.

PMID- 15732653
TI  - A meta-analytic review of the effects of high stress on eyewitness memory.
AB  - In the past 30 years researchers have examined the impact of heightened stress on
      the fidelity of eyewitness memory. Meta-analyses were conducted on 27 independent
      tests of the effects of heightened stress on eyewitness identification of the
      perpetrator or target person and separately on 36 tests of eyewitness recall of
      details associated with the crime. There was considerable support for the
      hypothesis that high levels of stress negatively impact both types of eyewitness
      memory. Meta-analytic Z-scores, whether unweighted or weighted by sample size,
      ranged from -5.40 to -6.44 (high stress condition-low stress condition). The
      overall effect sizes were -.31 for both proportion of correct identifications and
      accuracy of eyewitness recall. Effect sizes were notably larger for target
      present than for target-absent lineups, for eyewitness identification studies
      than for face recognition studies and for eyewitness studies employing a staged
      crime than for eyewitness studies employing other means to induce stress.

PMID- 15732654
TI  - A critical review of published competency-to-confess measures.
AB  - The development of standardized assessments for competency-to-confess evaluations
      has remained largely neglected for the last several decades. Groundbreaking
      research was conducted on Miranda waivers during the late 1970s, but researchers
      have failed to sustain programmatic research. This critical review focuses on
      four published Miranda measures (Comprehension of Miranda Rights, Comprehension
      of Miranda Rights-Recognition, Comprehension of Miranda Vocabulary, and Function
      of Rights in Interrogation). When evaluated by contemporary standards, the
      validation of these measures is very limited. Major improvements are needed for
      interrater reliability, test-retest reliability, content validity, construct
      validity, and criterion-related validity.

PMID- 15732655
TI  - Complications of the cardiopulmonary stress test in patients with depressed left
      ventricular systolic function.
AB  - BACKGROUND: The exercise test has a recognized lower risk of complications when
      used in the general population and in coronary artery diseased patients, but from
      a theoretical point of view should have a higher rate of complications when
      performed in patients with chronic heart failure (CHF). AIMS: To characterize and
      assess the type and incidence of complications during cardiopulmonary stress test
      (CPX) in patients with depressed left ventricular systolic function in comparison
      with a group of patients and individuals with normal function. METHODS:
      Retrospective analysis of the 334 consecutive CPX performed for risk
      stratification in 198 patients with a left ventricular ejection fraction below
      40% (Group A) and 180 consecutive CPX performed in 78 subjects with normal
      function (Group B). The two groups were compared with respect to demographic
      data, CPX parameters and specific complications. RESULTS: Major complications
      during the tests occurred only in 14 tests of Group A (4.2%, p = 0.012). Non
      sustained ventricular tachycardia, <6 beats, occurred in 7 group A and 2 group B
      tests. The absence of coronary artery disease was the only independent predictor
      for complications. CONCLUSIONS: Major CPX complications occurred only in patients
      with impaired left ventricular systolic function. Heart failure patients showed a
      low probability (around 4%) for complications during CPX, significantly higher
      and more severe than the risk in the group of patients with normal ventricular
      function, allowing us to recommend that CPX in patients with heart failure should
      be performed in a hospital setting under the supervision of a physician with
      specific training.

PMID- 15732656
TI  - Relationship between aortic stiffness and cardiovascular risk factors in a
      population of normotensives, white-coat normotensives, white-coat hypertensives,
      sustained hypertensives and diabetic patients.
AB  - OBJECTIVE: To evaluate the relationship between carotid-femoral pulse wave
      velocity (PWV) and office and ambulatory blood pressure (ABP) and other
      cardiovascular risk factors and to determine the discriminatory value of PWV in a
      large population including normotensive subjects (NT), white-coat normotensives
      (masked hypertension) (WCNT), and white-coat hypertensives (WCHT) compared to a
      group of treated and untreated hypertensive patients. METHODS: The study
      population included a total of 688 subjects aged from 18 to 80 years, with no
      previous cardiovascular events, who underwent 24 h ABP monitoring, biochemical
      evaluation and determination of PWV and left ventricular mass index (LVMI).
      Subjects were classified as true normotensives (NT, n=132; normal office and ABP
      values), WCNT (n=39; office BP < 140/90 and daytime BP > or =135 or > or =85
      mmHg), WCHT (n=87; office BP > or =140 or > or =90 and daytime BP < 135/85 mmHg).
      Untreated (UT-HT, n=154) and treated (T-HT, n=171) hypertensive patients and type
      2 diabetic patients (DM, n=102) were also studied. RESULTS: Values of PWV (m/s)
      in all groups were, in ascending order: NT (8.9 +/- 0.2) < WCHT (9.9 +/- 0.2) < T
      HT (11.4 +/- 0.2) = WCNT (11.5 +/- 0.4) < UT-HT (11.9 +/- 0.3) < DM (12.6 +/-
      0.4) (ANOVA, p = 0.043), and of LVMI (g/m2): NT (59 +/- 2) = WCHT (63 +/- 2) <
      WCNT (73 +/- 3) = T-HT (75 +/- 3) = UT-HT (77 +/- 3) < DM (84 +/- 4) (ANOVA, p <
      0.05). The percentage of subjects with PWV values below the median (10.7 m/s) was
      higher (p < 0.02) in NT (81.8%) and WCHT (72.6%) than in UT-HT (49.2%), T-HT
      (43.6%), WCNT (47.6%) and DM (27.7%). In multiple regression analysis, taking PWV
      as the dependent variable, age (all groups), 24h systolic BP (UT-HT, T-HT, WCNT
      and DM) and 24h diastolic BP (NT and WCHT) were the variables that independently
      influenced the PWV value. CONCLUSIONS: Higher values of PWV occur in clinical
      situations associated with higher cardiovascular risk. This is in agreement with
      risk stratification based on ABP values but not on office BP values. Lower PWV
      and LVMI values occur in NT and WCHT subjects, supporting a low cardiovascular
      risk in these groups. By contrast, higher PWV values were associated with higher
      ABP values in DM, hypertensive patients and white-coat normotensives, i.e.
      clinical situations that are associated with higher cardiovascular risk, who in
      the present study also exhibited higher LVMI than subjects with normal ABP
      values.

PMID- 15732657
TI  - Arterial distensibility, hypertensive disease and cardiovascular risk.

PMID- 15732658
TI  - Plasma N-terminal pro-brain natriuretic peptide: a marker of left ventricular
      hypertrophy in hypertrophic cardiomyopathy.
AB  - BACKGROUND: B-type natriuretic peptide is secreted mainly in the left ventricle
      in response to elevated wall tension. Plasma levels of the peptide correlate
      positively with cardiac filling pressures, making it an excellent marker for the
      presence of left ventricular dysfunction. In hypertrophic cardiomyopathy,
      enhanced production of B-type natriuretic peptide is observed. However, the
      relationship of the various structural and functional features present in the
      disease with the high plasma levels described is not yet fully clarified. In the
      present study, we prospectively assessed in hypertrophic cardiomyopathy the
      relationship of plasma NT-proBNP levels with the extent of left ventricular
      hypertrophy, presence of left ventricular outflow obstruction and
      echocardiographic parameters of left ventricular diastolic function. METHODS: The
      study population included 190 individuals: 53 patients with hypertrophic
      cardiomyopathy and well-preserved left ventricular systolic function (group A),
      92 healthy relatives with no disease expression (group B), and an additional
      group of 46 healthy volunteers (group C) as controls for NT-proBNP levels. Groups
      A and B were characterized clinically and by echocardiography and compared with
      each other. Plasma NT-proBNP levels were measured (ECLIA-Elecsys proBNP) and
      compared in the 3 groups of individuals included in the study. In hypertrophic
      cardiomyopathy patients, correlation was sought between NT-proBNP levels, NYHA
      functional class and echocardiographic data. RESULTS: Groups A and B differed (p
      < 0.001) in septal thickness, maximal wall thickness, left ventricular
      hypertrophy score, left atrial size, left atrial fractional shortening, derived
      transmitral filling indices and plasma NT-proBNP levels (group A: 909.9 +/-
      1554.2 pg/ml; group B: 40.7 +/- 45.1 pg/ml). Left ventricular diastolic size and
      pulmonary venous flow velocity-derived indices were similar in the 2 groups. NT
      proBNP levels in group B and C (39.4 +/- 34.5 pg/ml) were similar (p = NS). In
      hypertrophic cardiomyopathy patients, NT-proBNP levels correlate directly with
      NYHA functional class (r = 0.56, p < 0.001), septal thickness (r = 0.53, p <
      0.001), maximal wall thickness (r = 0.59, p < 0.001), left ventricular
      hypertrophy score (r = 0.63, p < 0.001), left atrial size (r = 0.32, p = 0.023)
      and mitral deceleration time (r = 0.46, p = 0.001) and inversely with left atrial
      fractional shortening (r = -0.41, p = 0.005). Functional class also correlates
      directly with left ventricular hypertrophy score (r = 0.39, p = 0.006), with the
      most symptomatic patients having the highest scores. CONCLUSIONS: In hypertrophic
      cardiomyopathy, plasma NT-proBNP levels depend mainly on the severity of left
      ventricular hypertrophy rather than on the presence of obstruction. Measurement
      of the peptide may help in the clinical characterization and follow-up of
      patients with this disease.

PMID- 15732659
TI  - Acute myocardial infarction in patients aged under 45 years.
AB  - INTRODUCTION: Coronary artery disease (CAD) becomes an important cause of
      morbidity and mortality after the age of 45 years. OBJECTIVE: To evaluate the
      epidemiology and clinical features of all patients under 45 years old admitted
      with myocardial infarction. METHODS: We studied 595 patients admitted with
      myocardial infarction between January 2000 and December 2002. We analyzed risk
      factors for CAD, clinical profile, therapeutics and complications (arrhythmic,
      mechanical and ischemic). The patients were divided into two groups: A--under 45
      years old and B-- aged 45 or over. RESULTS: Group A--56 patients (9.4%); group B-
      539 patients (90.6 %). There was a higher prevalence of smoking in group A (57%
      vs. 23.6%; p < 0.01). Hypertension, diabetes and history of CAD were
      significantly more common in group B. There were no differences in hyperlipidemia
      (group A: 43% vs. group B: 43.5%). Fibrinolysis was performed in 28 patients
      (70%) from group A compared to 40 patients (45.9%; p < 0.01) from group B. Use of
      digitalis and inotropic agents was greater in group B. No differences were found
      in other pharmacological therapeutics. We found more complications in group B
      (24% vs. 11%). CONCLUSIONS: There was a higher prevalence of smoking in patients
      under 45 years old and of hypertension, diabetes and CAD in patients aged over
      45. The high rate of hyperlipidemia in both groups highlights the importance of
      primary prevention. Fibrinolysis was performed more frequently in younger
      patients. There were more complications in older patients.

PMID- 15732660
TI  - [Angiotensin converting enzyme gene polymorphisms and coronary risk in a
      Portuguese population].
AB  - BACKGROUND: A family history of coronary heart disease (CHD) is a strong risk
      marker for the disease, independently of classical risk factors. It could be
      decoded by recognizing the polymorphisms associated with increased risk. Renin
      angiotensin system genes are candidate genes in CHD and the deletion allele of
      the angiotensin converting enzyme (ACE) has been reported as deleterious.
      However, there is disagreement as to the role of the insertion/deletion
      polymorphism of the ACE gene in coronary risk. AIM: To evaluate whether ACE gene
      polymorphisms constitute a CHD risk factor. METHODS: We conducted a population
      based case-control study of 301 subjects with a history of myocardial infarction
      or angiographic evidence of coronary heart disease and 510 age- and gender
      matched controls, without CHD, living in a region with high CHD mortality rates.
      Blood samples were taken, DNA extracted and genotypes determined by the
      polymerase chain reaction (PCR). Amplification products were identified by
      agarose gel electrophoresis. STATISTICAL ANALYSIS: The Data were evaluated by
      SPSS for Windows, using the Student's t test, the chi-square test, odds ratios
      and 95% confidence intervals. RESULTS: The prevalence of the DD, ID and II
      genotype was 41.2%, 46.3%, 12.5% in the cases and 28.1%, 55.2% and 16.7% in the
      control group. The frequency of the DD genotype was significantly higher in the
      cases than in the controls (41.2% vs. 28.1%, odds ratio 1.79, 95% CI 1.31 to 2.4,
      p < 0.0001). By contrast, the ID and II genotypes' prevalence was higher in the
      control group (55.2% vs. 46.3%, p = 0.002 and 16.7 vs. 12.5%, p = NS,
      respectively) compared to the case group. CONCLUSIONS: This study clearly shows
      that the ACE DD polymorphism is strongly linked to CHD, and if our data are
      confirmed in a larger population sample, more aggressive vascular prevention
      could be justified in patients carrying the DD genotype.

PMID- 15732661
TI  - Polymorphism of the ACE gene is associated with extent and severity of coronary
      disease.
AB  - BACKGROUND: The progression and extent of coronary heart disease (CHD) are
      extremely variable and in many instances independent of conventional risk
      factors. The differences may be partly explained by less favorable genetic
      polymorphisms that are associated with them. The polymorphisms of the angiotensin
      I converting enzyme (ACE) gene have been thoroughly evaluated, but the connection
      between them and the extent of CHD is unknown. AIMS: Our study is aimed at
      determining whether any or all of the polymorphisms of the ACE gene are markers
      of the extent and severity of CHD. METHODS: This was a descriptive study of 296
      patients with a history of myocardial infarction or with coronary disease
      confirmed by coronary angiography. The severity of CHD was quantified according
      to Leaman's score (based on the number of arteries with more than 75% reduction
      in diameter and the number of affected coronary segments). The ACE genotypes were
      determined by specific polymerase chain reaction amplification and the segments
      were subjected to polyacrylamide gel electrophoresis. The mean coronary score and
      standard deviation of the three polymorphisms were calculated and the values
      statistically compared using the Student's t test for independent samples.
      RESULTS: 296 patients with a mean age of 55.103 years, 234 male, were evaluated.
      CONCLUSION: The study clearly shows that the DD genotype is linked to the extent
      of CHD, with a high level of significance. If this is confirmed, careful
      secondary prevention is indicated in patients with this genotype.

PMID- 15732662
TI  - Independent origin of all three coronary arteries from the right coronary sinus.
AB  - We present a case of a patient who underwent coronary angiography in a setting of
      acute myocardial infarction, which showed an independent origin of all three
      coronary arteries from the right coronary sinus. This has rarely been described
      in the medical literature.

PMID- 15732663
TI  - Antihypertensive pharmacogenetics.
AB  - Essential hypertension is a complex disease in which multiple genetic and
      environmental factors interact to produce the phenotype. The genetic contribution
      to blood pressure variations is estimated to range from 30% to 50%. In this
      review we describe some of the genes and genetic polymorphisms that have been
      most consistently related to blood pressure elevation and also the importance of
      pharmacogenetics and the emerging evidence of genetic influences on
      antihypertensive drug responses, with the potential for getting the right drug
      into the right patient based on the individual genetic profile.

PMID- 15732664
TI  - Screening for coronary artery disease in assymptomatic adults is not recommended,
      so why is it still done?
AB  - The rationale behind screening for asymptomatic coronary artery disease is that
      it may diagnose advanced disease that, while frequently without symptoms, may
      present for the first time as sudden death. Identifying significant coronary
      artery disease would enable intervention against risk factors and, if necessary,
      preventive revascularization. The most recent evidence shows that screening for
      coronary artery disease with resting electrocardiogram, exercise tolerance
      testing or electron-beam computerized tomography in low-risk patients does more
      harm than good, and should not be performed. This negative recommendation is
      based on the fact that the use of the aforementioned tests has a negative benefit
      harm ratio, because the false-positive rate cancels out any benefit from the
      occasional detection of real disease, inducing a cascade of further testing
      (sometimes with angiography) and overdiagnosis of a disease that is not in fact
      present, with negative psychological and financial consequences, such as
      increased insurance premiums. We feel that the Portuguese Society of Cardiology
      should intervene with the institutions performing screening of coronary heart
      disease in asymptomatic patients, and recommend abandoning a practice that is of
      little use and, overall, harmful.

PMID- 15732665
TI  - Fabry disease--evaluation by cardiac magnetic resonance imaging.

PMID- 15732666
TI  - [Epidemiology for the citizens of the world].

PMID- 15732667
TI  - [More attention to veterinarian epidemiologists].

PMID- 15732668
TI  - [Epidemiology and war].

PMID- 15732669
TI  - [Assessment of causes and consequences of violence in war: start with a field
      choice].

PMID- 15732671
TI  - [Comments on Giulio Maccacaro and attributable risks to chemical agents].

PMID- 15732670
TI  - [Caesarian section: research and policy making].

PMID- 15732672
TI  - [Pharmaceutical expense, monitoring and scandals].

PMID- 15732673
TI  - [The future of European collaborative research in epidemiology and public health:
      time has come for epidemiologists to take action].

PMID- 15732674
TI  - [Exposure to PCB/dioxine in Brescia: comments to the Local Health Unit's Report].

PMID- 15732675
TI  - [Comparison of stillbirth and neonatal mortality in two Italian regions:
      Lombardia and Campania].
AB  - OBJECTIVE: To compare fetal and neonatal mortality in two Italian regions,
      characterized by different socio-economic factors and health care organisations,
      and to study the main maternal and fetal determinants of mortality. DESIGN:
      Cohort study. Distributions of births in 1995-1996 by birthweight and gestational
      age are described and stillbirth, perinatal and neonatal mortality are analysed
      and compared. The determinants of mortality (birthweight, gestational age,
      sociodemographic maternal characteristics and type of delivery) have been
      analysed using logistic regression models. SETTING: Two Italian regions with the
      highest number of births, Lombardia and Campania. The first represents the
      industrialized northern Italy, the second the relatively poorly developed
      southern Italy. PARTICIPANTS: The analysis concerns 300,697 births, 156,436 of
      which in Lombardia and 144,261 in Campania. MAIN OUTCOME MEASURES: Stillbirth,
      perinatal and neonatal mortality rates. RESULTS: The percentage of low
      birthweight (<2,500 grams) is the same in both regions, that is, 5.2%. The
      percentage of preterm births is higher in Lombardia than in Campania (5.5% vs
      3.9%). Stillbirth, perinatal and neonatal mortality rates are lower in Lombardia
      than in Campania, that is: 3.6 per thousand and 4.2 per thousand; 5.8 per
      thousand and 7.6 per thousand; 2.9 per thousand and 4.4 per thousand
      respectively. CONCLUSION: The comparison between the two regions highlights the
      different role played by the various main determinants. In particular, the
      gestational age seems to be more important in Campania than in Lombardia, as it
      is for the neonatal mortality The analysis provides us with some useful elements
      strictly related to the delivery characterisitcs and consequently to the kind of
      health care organisation to explain mortality differences between the two
      regions.

PMID- 15732676
TI  - [Road traffic accidents in the province of Udine: estimation of drivers' injuries
      attributable to personal, environmental, and vehicle-related factors].
AB  - OBJECTIVE: To estimate injuries attributable to personal, environmental, and
      vehicle-related factors among drivers involved in road accidents in the province
      of Udine. DESIGN: Analysis of data contained in the ISTAT road accident reports.
      SETTING: Road traffic accidents with personal damage that occurred in the
      province of Udine from 1991 to 1998. MAIN OUTCOME MEASURES: Fractions of injuries
      and deaths attributable to various risk factors. RESULTS: From 1991 to 1998,
      24261 drivers were involved in accidents: 462% were uninjured, 51.8% were non
      fatally injured, and 2.0% died within 7 days. The greatest proportion of injuries
      (10.59%) was attributed to being on a two-wheeled vehicle. On the other hand,
      with respect to death the highest proportion of cases was attributed to driving
      during the night (29.19%) and to non-using seat belts and helmets (26.30%).
      CONCLUSIONS: This study provides information useful for establishing priorities
      for the prevention of road accidents and injuries.

PMID- 15732677
TI  - [The database of the Italian cancer registries: estimates of the observed
      populations].
AB  - OBJECTIVES: Building a database with the estimates of the observed populations of
      the Italian Cancer Registries (CR), subdivided into sex, annual age classes and
      calendar year; making this population database available in the AIRT website;
      making available an Excel file that allows the input of a population by 5-year
      age classes in order to obtain an esteem of the annual classes. DESIGN:
      Employment of different interpolation methods, namely annual age classes starting
      from 5-year classes, an esteem of the final open class of 85 years and over.
      PARTICIPANTS: 17 CRs that take part to the incidence and mortality trend study
      promoted by AIRT in 2003. SETTING: AIRT. MAIN OUTCOME: A database of the
      estimated populations observed by the CRs by sex and annual age classes on 31
      December of each incidence year. RESULTS: Only for 6 on 17 CRs taking part in the
      AIRT trend terpolation methods have been used. The performance of these methods,
      tested with an empirical measure of error called WMISE, have given good results,
      even if in the elderly classes the fit is poor and sometimes not sufficient.
      CONCLUSIONS: Different interpolation methods have been used to build and make
      available a database containing reliable data of population, in order to use them
      as denominators for the incidence and mortality trend analysis. It is also
      available an Excel file that allows the input of a population by 5-year age
      classes in order to obtain an esteem of the annual classes.

PMID- 15732678
TI  - [Mortality study of asbestos cement workers in Emilia-Romagna].
AB  - OBJECTIVE: The present study updates to 06/30/1998 the cohort mortality study of
      3358 workers employed in 10 asbestos cement production plants in the Italian
      region Emilia-Romagna. PARTICIPANTS: The cohort includes 2712 males and 646
      females. RESULTS: Overall mortality was significantly increased (SMR=131,
      IC95%:108-127). Excess mortality has been observed for all malignant neoplasms
      (SMR=131, IC95%: 115-149, 250 observed) and for respiratory diseases (SMR=153,
      IC: 105-216, 32 observed), 3 deaths due to asbestosis. Mortality for all
      respiratory tract neoplasms (SMR=179, IC: 148-215, 114 observed), pulmonary
      cancer (SMR=157, IC: 126-192, 90 observed) and pleural cancer (SMR=1922, IC: 1139
      3038, 18 observed) are significantly increased. DISCUSSION: This study confirms
      the previous cohort study observation of increased mortality for all causes, all
      neoplasm and cancer affecting lungs and pleura.

PMID- 15732679
TI  - [Estimate of cancer incidence in Italian regions, 2001].
AB  - AIM: The purpose of the present paper is to calculate cancer incidence estimates
      in the italian regions for the year 2001. DESIGN: Estimates are computed
      according to the mortality/incidence (M/I) ratio method. Observed data were from
      Italian areas covered by cancer registration and recently published by Cancer
      Registries Network (1993-1998), by the Italian National Institute of Health
      (ISS), that published mortality statistics for the year 1998, and by the National
      Institute of Statistics (Istat) that provided population figures for the year
      2001. Regression coefficients of the M/I ratios specific by cancer site, age
      class, sex and geographical area were computed and then applied to the observed
      mortality in the Italian regions in the year 1998. The estimated number of new
      cancer cases was then computed multiplying the estimated rates for the regional
      populations in the year 2001, as published by Istat. RESULTS: The total number of
      estimated new cancers (with the exclusion of skin cancers) in Italy was
      approximately 160,000 in men and 130,000 in women. The population of the Liguria
      region, older than other Italian regional populations, showed the highest crude
      rates, while its risk is similar compared to other Northern regions, as indicated
      by age-standardised rates. The most frequent tumour sites are the lung cancer
      (29,500 cases), the colon-rectum cancer (19,900 cases) and the prostate cancer
      (19,600 cases) in men; the breast cancer (35,000 cases), the colon-rectum cancer
      (19,500 cases) and the stomach cancer (6,800 cases) in women. The invasive
      cervical cancer, largely preventable with early diagnosis, is still responsible
      for approximately 3,000 new cases yearly. CONCLUSION: Incidence estimates are a
      useful tool for a better management of health resources. Treatment costs for
      tumour patients are generally high in the first period for diagnosis and
      principal treatment, while they fade during follow-up and remission. Costs
      increase during the terminal phase of disease. In the first period, costs can be
      predicted thanks to incidence estimates, while in the last period mortality data
      are more useful.

PMID- 15732680
TI  - [Breathing difficulties and asthma prevalence in children from zero to five years
      of age in five Rom settlements].
AB  - OBJECTIVE: To study the relation between living conditions in temporary Rom
      settlements and asthma prevalence in children. DESIGN: Purposive cluster (Rom
      settlements) sampling. SETTING: Five settlements of Rom from Macedonia and Kosovo
      located in five cities in northern and central Italy. These settlements were
      chosen to represent the different types of existing living arrangements.
      PARTICIPANTS: 137 Rom families residing in the selected settlements. In total 737
      people were covered, of which 167 were children from zero to five years of age.
      MAIN OUTCOME MEASURES: Respiratory wheezing, breathing difficulties during
      lifetime and number of episodes in the last 12 months. Asthma diagnosis and
      period prevalence. RESULTS: The comparison with the data of the SIDRIA study for
      children aged 6-7 confirms the reliability of the results we are presenting.
      However, the study reveals a higher incidence of asthma symptoms in Rom children
      which could lead to a worse asthma prognosis in later years. Moreover, the
      prevalence of asthma and the incidence of asthma symptoms in the last year vary
      significantly according to the settlement of origin and the state of the housing
      in which the child lives. CONCLUSION: The health of Rom children who live in
      settlements is put under great strain by the poor state of repair of the majority
      of these structures. It is therefore necessary to overcome the "emergency"
      approach and the "temporary" nature of the measures taken so far to deal with the
      issue of Rom from Eastern Europe, and plan serious reception and integration
      policies.

PMID- 15732681
TI  - [Soft tissue sarcomas in Mantua: epidemiological evidence and perspectives for
      environmental remediation].
AB  - Subsequently to the report by a general practitioner of an apparent cluster of
      soft tissue sarcomas (STS) in thepopulation resident in the neighbourhood of
      Mantua chemical industries, two independent epidemiological studies (an incidence
      study and a case-control study) confirmed the original observation and extended
      the findings in a wider time-span. The two studies are reviewed in the present
      paper in order to analyze concordant and diverging findings. In the light of the
      available evidence, recommendations for further studies are presented and
      perspectives of environmental remediation are discussed.

PMID- 15732682
TI  - [Presenting results of stochastic economic evaluations].

PMID- 15732683
TI  - [Dossier SALeM: a method for assessing the effectiveness of a public health
      program].
AB  - The SALeM (Surveillance for apprentices and minors at work) is the first dossier
      aimed at evaluating the effectiveness of a public health program in Italy. Here
      we describe the main results achieved and the main methodological difficulties
      faced during its gathering. Aim of the dossier was to collect and weigh up all
      the available evidence of effectiveness referred to the program of health
      surveillance of apprentices and minors at work in non risky environments, as it
      is planned by the Italian National Health System. We chose this subject for
      feasibility reasons (given the limited resources available), and for its
      paradigmatic essence (we applied the methodology for the first time). The results
      achieved stress the standing difficulties in public health when the effectiveness
      evaluation of a running program is necessary. Broadest possibilities of deeper
      evaluation are more feasible for programs implemented ex novo. Authors conclude
      that, anyhow, when evaluating the effectiveness of public health program
      introduced ex novo the experience of Italy is still under construction and
      knowledge has to be lended from foreign countries.

PMID- 15732684
TI  - [Health education at school: we need more than a new discipline].

PMID- 15732685
TI  - [Active and passive smoking: two sides of the same medal].
AB  - The authors underline the similarities between active and passive smoking under
      many features, i.e. chemical and physical composition, the kind of health risks,
      the anti-educational impact on the youth. The special character of passive
      smoking is also discussed, such as its multiplicative exposure effect on the
      population, and the hazard to high-risk people like children, pregnant women, and
      respiratory and cardiovascular patients.

PMID- 15732686
TI  - [Symbolic sunnah, a project fit for the local setting].

PMID- 15732687
TI  - Time does not cause forgetting in short-term serial recall.
AB  - Time-based theories expect memory performance to decline as the delay between
      study and recall of an item increases. The assumption of time-based forgetting,
      central to many models of serial recall, underpins their key behaviors. Here we
      compare the predictions of time-based and event-based models by simulation and
      test them in two experiments using a novel manipulation of the delay between
      study and retrieval. Participants were trained, via corrective feedback, to
      recall at different speeds, thus varying total recall time from 6 to 10 sec. In
      the first experiment, participants used the keyboard to enter their responses but
      had to repeat a word (called the suppressor) aloud during recall to prevent
      rehearsal. In the second experiment, articulation was again required, but recall
      was verbal and was paced by the number of repetitions of the suppressor in
      between retrieval of items. In both experiments, serial position curves for all
      retrieval speeds overlapped, and output time had little or no effect. Comparative
      evaluation of a time-based and an event-based model confirmed that these results
      present a particular challenge to time-based approaches. We conclude that output
      interference, rather than output time, is critical in serial recall.

PMID- 15732688
TI  - Likelihood ratios: a simple and flexible statistic for empirical psychologists.
AB  - Empirical studies in psychology typically employ null hypothesis significance
      testing to draw statistical inferences. We propose that likelihood ratios are a
      more straightforward alternative to this approach. Likelihood ratios provide a
      measure of the fit of two competing models; the statistic represents a direct
      comparison of the relative likelihood of the data, given the best fit of the two
      models. Likelihood ratios offer an intuitive, easily interpretable statistic that
      allows the researcher great flexibility in framing empirical arguments. In
      support of this position, we report the results of a survey of empirical articles
      in psychology, in which the common uses of statistics by empirical psychologists
      is examined. From the results of this survey, we show that likelihood ratios are
      able to serve all the important statistical needs of researchers in empirical
      psychology in a format that is more straightforward and easier to interpret than
      traditional inferential statistics.

PMID- 15732689
TI  - Merging race models and adaptive networks: a parallel race network.
AB  - This article presents a generalization of race models involving multiple
      channels. The major contribution of this article is the implementation of a
      learning rule that enables networks based on such a parallel race model to learn
      stimulus-response associations. This model is called a parallel race network.
      Surprisingly, with a two-layer architecture, a parallel race network learns the
      XOR problem without the benefit of hidden units. The model described here can be
      seen as a reduction-of-information system (Haider & Frensch, 1996). An emergent
      property of this model is seriality: In some conditions, responses are performed
      with a fixed order, although the system is parallel. The mere existence of this
      supervised network demonstrates that networks can perform cognitive processes
      without the weighted sum metric that characterizes strength-based networks.

PMID- 15732690
TI  - The owl and the pussycat: gaze cues and visuospatial orienting.
AB  - Recent research has shown that nonpredictive gaze cues trigger reflexive shifts
      in attention toward the looked-at location. But just how generalizable is this
      spatial cuing effect? In particular, are people especially tuned to gaze cues
      provided by conspecifics, or can comparable shifts in visual attention be
      triggered by other cue providers and directional cues? To investigate these
      issues, we used a standard cuing paradigm to compare the attentional orienting
      produced by different cue providers (i.e., animate vs. inanimate) and directional
      cues (i.e., eyes vs. arrows). The results of three experiments revealed that
      attentional orienting was insensitive to both the identity of the cue provider
      and the nature of the triggering cue. However, compared with arrows, gaze cues
      prompted a general enhancement in the efficiency of processing operations. We
      consider the implications of these findings for accounts of reflexive visual
      orienting.

PMID- 15732691
TI  - Very clever homunculus: compound stimulus strategies for the explicit task-cuing
      procedure.
AB  - In two experiments, subjects were given arbitrary letter cues or meaningful word
      cues that specified the task to be performed on a subsequent target stimulus.
      Letter and word cues were presented in separate blocks. There were two cues of
      each type for each task. Three kinds of transitions separated tasks: cue
      repetitions, in which both the cue and the task repeated; task repetitions, in
      which the cue changed but the task repeated; and task alternations, in which both
      the cue and the task changed. Responses were faster for cue than for task
      repetitions for both cue types. With word cues, task repetitions were not
      reliably faster than task alternations. With letter cues, task repetitions were
      reliably faster than task alternations in the first block but not in the second
      block. The results suggest that subjects responded to the compound of the cue and
      the target rather than switching task set between trials.

PMID- 15732692
TI  - Stimulus-response compatibility with wheel-rotation responses: will an
      incompatible response coding be used when a compatible coding is possible?
AB  - Three experiments were conducted in which subjects responded to left-right tones
      with clockwise-counterclockwise rotations of a steering wheel using one of two
      stimulus-response assignments. When the hands were at the bottom of the wheel,
      where hand movement is opposite to wheel movement, subjects coded responses
      according to the frame that yielded a compatible mapping when the instructions
      did not emphasize either hand or wheel movements (Experiment 1). When
      instructions emphasized hand movements, responses were coded relative to the hand
      referenced frame (Experiment 2), and when the wheel controlled a visual cursor,
      responses were coded relative to a cursor-referenced frame (Experiment 3). Coding
      with respect to these frames occurred even when the resulting mapping was
      incompatible.

PMID- 15732693
TI  - Attentional load modulates mislocalization of moving stimuli, but does not
      eliminate the error.
AB  - Localization of the onset and offset of a moving target is subject to a number of
      errors that have to be attributed to events following or preceding the target
      event. Apparently, observers are unable to ignore the spatiotemporal context
      surrounding the target event. In two experiments, observers' attention was
      directed toward a single position along a trajectory, two positions along a
      single trajectory, or two positions along two different trajectories. In the
      latter condition, attention to details of a single trajectory was reduced. At the
      same time, motion type was manipulated by varying the temporal interval between
      successive target presentations. The localization error was not affected by
      attentional load; however, effects of motion type were eliminated when two
      trajectories had to be attended to. It may be sufficient to notice that the
      target has moved for localization errors to occur, while specifics of the
      trajectory are ignored.

PMID- 15732694
TI  - Automatic and intentional memory processes in visual search.
AB  - Previous research has indicated that saccade target selection during visual
      search is influenced by scanning history. Already inspected items are less likely
      to be chosen as saccade targets as long as the number intervening saccades is
      small. Here, we adapted Jacoby's (1991) process dissociation procedure to assess
      the role of intentional and automatic processes in saccade target selection.
      Results indicate a large automatic component biasing participants to move their
      eyes to unexamined locations. However, an intentional component allowed
      participants to both reinspect old items and aid their selection of new items. A
      second experiment examined inhibition of return (IOR) as a candidate for the
      observed automatic component. IOR was found for items that had been previously
      examined. It is concluded that both automatic and intentional memory traces are
      available to guide the eyes during search.

PMID- 15732695
TI  - Are there capacity limitations in symmetry perception?
AB  - Previous researchers have proposed that there are two types of symmetry
      detection: one based on crude preattentive symmetry judgments and another based
      on detailed scrutiny of individual parts (Barlow & Reeves, 1979; S. E. Palmer &
      Hemenway, 1978; Royer, 1981). Four experiments were conducted to examine capacity
      limits in different symmetry judgments. Observers were required to discriminate
      between random patterns and approximate symmetry (Experiments 1 and 3) or between
      perfect and approximate symmetry (Experiments 2 and 4). The patterns were divided
      into two sets of dots, presented either simultaneously or successively. A
      comparison of accuracy under these two presentation conditions suggested that
      symmetry detection involves an analysis that is spatially parallel but coarse,
      regardless of either task difficulty or task type (detecting symmetry vs.
      detecting asymmetry).

PMID- 15732696
TI  - Changing features do not guide attention in change detection: evidence from a
      spatial cuing paradigm.
AB  - Smilek, Eastwood, and Merikle (2000) demonstrated that the detection of change
      was facilitated when the target character changed in many rather than few of its
      features. Specifically, the function relating search response time to display set
      size was shallower when more features changed than when fewer features changed.
      The researchers interpreted these results as indicating that large feature
      changes provide preattentive guidance of focal attention to the location of the
      change. We tested this preattentive guidance hypothesis by examining change
      detection performance in the context of a spatial cuing paradigm. The hypothesis
      predicts that (1) the cost on invalidly cued trials should be less when more
      features change than when fewer features change, and (2) the features
      manipulation should have no effect on validly cued trials. In contrast to these
      predictions, our results show that cuing effects are equivalent across all levels
      of feature change and that a robust effect of the features manipulation is
      observable for both validly and invalidly cued trials. We argue that large
      feature changes do not provide preattentive guidance and in fact can be detected
      more readily after attention is already in place at the target location.

PMID- 15732697
TI  - Searching for stimulus-driven shifts of attention.
AB  - Several types of dynamic cues (e.g., abrupt onsets, motion) draw attention in
      visual search tasks even when they are irrelevant. Although these stimuli appear
      to capture attention in a stimulus-driven fashion, typical visual search tasks
      might induce an intentional strategy to focus on dynamic events. Because
      observers can only begin their search when the search display suddenly appears,
      they might orient to any dynamic display change (Folk, Remington, & Johnston,
      1992; Gibson & Kelsey, 1998). If so, the appearance of capture might result from
      task-induced biases rather than from the properties of the stimulus. In fact,
      such biases can even create the appearance of stimulus-driven capture by stimuli
      that typically do not capture attention (Gibson & Kelsey, 1998). The possibility
      of task-induced, top-down biases plagues the interpretation of all previous
      studies claiming stimulus-driven attention capture by dynamic stimuli. In two
      experiments, we attempt to eliminate potential task-induced biases by removing
      any need to monitor for display changes. In the first experiment, search displays
      did not change on most trials. In the second experiment, although new search
      displays appeared on each trial, we ensured that observers never saw the changes,
      by making them during large saccades. In both cases, dynamic events still
      received search priority, suggesting that some dynamic stimuli capture attention
      in a stimulus-driven fashion.

PMID- 15732698
TI  - Linguistic focus and good-enough representations: an application of the change
      detection paradigm.
AB  - A number of lines of study suggest that word meanings are not always fully
      exploited in comprehension. In two experiments, we used a text-change paradigm to
      study depth of semantic processing during reading. Participants were instructed
      to detect words that changed across two consecutive presentations of short texts.
      The results suggest that the full details of word meanings are not always
      incorporated into the interpretation and that the degree of semantic detail in
      the representation is a function of linguistic focus. The results provide
      evidence for the idea that representations are only good enough for the purpose
      at hand (Ferreira, Bailey, & Ferraro, 2002).

PMID- 15732699
TI  - Discriminative stimuli that follow a delay have added value for pigeons.
AB  - Clement, Feltus, Kaiser, and Zentall (2000) reported that pigeons prefer
      discriminative stimuli that require greater effort (more pecks) to obtain over
      those that require less effort. In the present experiment, we examined two
      variables associated with this phenomenon. First, we asked whether delay of
      reinforcement, presumably a relatively aversive event similar to effort, would
      produce similar effects. Second, we asked whether the stimulus preference
      produced by a prior relatively aversive event depends on its anticipation.
      Anticipation of delay was accomplished by signaling its occurrence. Results
      indicated that delays can produce preferences similar to those produced by
      increased effort, but only if the delays are signaled.

PMID- 15732700
TI  - View sensitivity increases for same-shape matches if mismatches show pairs of
      more similar shapes.
AB  - Lawson, Bulthoff, and Dumbell (2003) found increased view sensitivity when more
      similar shapes had to be discriminated. Their sequential picture-picture matching
      studies showed depth-rotated views of novel, complex, 3-D objects. However, with
      a similar task and stimuli, Hayward and Williams (2000) found no variation in
      view sensitivity on same-shape match trials depending on whether similar or
      dissimilar pairs of shapes were shown on mismatch trials. Thus view sensitivity
      increases from dissimilar-shape mismatches to similar-shape mismatches to same
      shape matches (Lawson et al., 2003). However, view sensitivity may not increase
      on same-shape matches if those trials are combined with similar-rather than
      dissimilar-shape mismatches (Hayward & Williams, 2000). The latter result was
      reexamined here. Matches were view sensitive given even the dissimilar-shape
      mismatch context. This view sensitivity increased in the medium and especially
      the hard contexts that showed similar shapes on mismatches. Thus, indirectly
      increasing shape similarity via mismatch context modulated view-change effects
      (cf. Hayward & Williams, 2000).

PMID- 15732701
TI  - Recognition without picture identification: geons as components of the pictorial
      memory trace.
AB  - Participants viewed a list of black-and-white line drawings and were then
      presented with a picture fragment identification task in which half of the
      fragments corresponded to studied pictures and half corresponded to unstudied
      pictures. In addition to trying to identify each picture fragment, participants
      gave a rating to indicate the likelihood that the fragment came from a studied
      picture. When participants could not identify the picture fragments, they were
      still able to discriminate between fragments that came from studied pictures and
      fragments that came from unstudied pictures (as shown by their recognition
      ratings), but only when the fragments contained information about the geometric
      components (geons) that underlay the original pictures. No recognition without
      identification was found when the fragments contained only line segment
      information.

PMID- 15732702
TI  - The reference frame of figure-ground assignment.
AB  - Figure-ground assignment involves determining which visual regions are foreground
      figures and which are backgrounds. Although figure-ground processes provide
      important inputs to high-level vision, little is known about the reference frame
      in which the figure's features and parts are defined. Computational approaches
      have suggested a retinally based, viewer-centered reference frame for figure
      ground assignment, but figural assignment could also be computed on the basis of
      environmental regularities in an environmental reference frame. The present
      research used a newly discovered cue, lower region, to examine the reference
      frame of figure-ground assignment. Possible reference frames were misaligned by
      changing the orientation of viewers by having them tilt their heads (Experiments
      1 and 2) or turn them upside down (Experiment 3). The results of these
      experiments indicated that figure-ground perception followed the orientation of
      the viewer, suggesting a viewer-centered reference frame for figure-ground
      assignment.

PMID- 15732703
TI  - Selective attention and asymmetry in the Muller-Lyer illusion.
AB  - Two experiments reexamined the effect of selective spatial attention on the
      magnitudes of the wings- in and wings-out forms of the Muller-Lyer (M-L) illusion
      and a version of the illusion in which the two forms are superimposed to produce
      a figure (XX) flanked at both ends by an X. For the XX figure, ignoring the outer
      wings produced significant underestimation of shaft length, whereas ignoring the
      inner wings had no significant effect. For the M-L figures, ignoring the wings
      was more effective in attenuating the magnitude of the wings-out than of the
      wings-in illusion. The results are discussed with reference to space-based
      approaches to visual attention and to claims that attentional modulation of
      illusion magnitudes implicates high-level or cognitive factors in the formation
      of the M-L illusion.

PMID- 15732704
TI  - Age differences in veridical and false recall are not inevitable: the role of
      frontal lobe function.
AB  - The relationship of neuropsychological measures of frontal lobe function to age
      differences in false recall was assessed using the Deese/Roediger-McDermott
      associative false memory paradigm (Deese, 1959; Roediger & McDermott, 1995). As
      other studies have found, older adults were less likely to correctly recall
      studied items and more likely to falsely recall highly related but nonpresented
      items than were younger adults. When older adults were divided based on a
      composite measure of frontal lobe functioning, this age difference was found only
      for low frontal lobe functioning individuals. High frontal lobe functioning older
      adults and young adults had equivalent levels of false recall, as well as
      equivalent levels of veridical recall. These results suggest that age differences
      in memory may be due to declines in frontal lobe function. More important, our
      findings indicate that declines in veridical recall and increases in false recall
      are not an inevitable consequence of aging.

PMID- 15732705
TI  - An event-related potential study of the revelation effect.
AB  - Event-related potentials (ERPs) were recorded during a verbal recognition memory
      task in order to investigate whether changes in familiarity are part of the
      explanation for the revelation effect. For half of the test words, participants
      solved an anagram prior to making the old/new recognition judgment. A revelation
      effect was obtained: When test words were preceded by the anagram task, a higher
      probability of an old response was associated with the items than was otherwise
      the case. The ERPs recorded time-locked to the onset of the test words were
      separated according to old/new status andthe presence/absence of the anagram
      task. The ERP index of familiarity was of lower amplitude for both old and new
      items that were preceded by the anagram task. These findings are consistent with
      the view that part of the explanation for the revelation effect is a reduction in
      the familiarity of the critical test items.

PMID- 15732706
TI  - The role of memory representation in the vigilance decrement.
AB  - Working memory load is critically important for the overall level of performance
      on vigilance tasks. However, its role in a key aspect of vigilance-sensitivity
      decrement over time-is unclear. We used a dual-task procedure in which either a
      spatial or a nonspatial working memory task was performed simultaneously with a
      spatial vigilance task for 20 min. Sensitivity in the vigilance task declined
      over time when the concurrent task involved spatial working memory. In contrast,
      there was no sensitivity decrement with a nonspatial working memory task. The
      results provide the first evidence of a specific role for working memory
      representation in vigilance decrement. The findings are also consistent with a
      multiple resource theory in which separate resources for memory representation
      and cognitive control operations are differentially susceptible to depletion over
      time, depending on the demands of the task at hand.

PMID- 15732707
TI  - Learning in a unidimensional absolute identification task.
AB  - We tested whether there is long-term learning in the absolute identification of
      line lengths. Line lengths are unidimensional stimuli, and there is a common
      belief that learning of these stimuli quickly reaches a low-level asymptote of
      about seven items and progresses no more. We show that this is not the case. Our
      participants served in a 1.5-h session each day for over a week. Although they
      did not achieve perfect performance, they continued to improve day by day
      throughout the week and eventually learned to distinguish between 12 and 20 line
      lengths. These results are in contrast to common characterizations of learning in
      absolute identification tasks with unidimensional stimuli. We suggest that this
      learning reflects improvement in short-term processing.

PMID- 15732708
TI  - Evidence for a procedural-learning-based system in perceptual category learning.
AB  - The consistency of the mapping from category to response location was
      investigated to test the hypothesis that abstract category labels are learned by
      the hypothesis testing system to solve rule-based tasks, whereas response
      position is learned by the procedural-learning system to solve information
      integration tasks. Accuracy rates were examined to isolate global performance
      deficits, and model-based analyses were performed to identify the types of
      response strategies used by observers. A-B training (consistent mapping) led to
      more accurate responding relative to yes-no training (variable mapping) in the
      information-integration category learning task. Model-based analyses indicated
      that the yes-no accuracy decline was due to an increase in the use of rule-based
      strategies to solve the information-integration task. Yes-no training had no
      effect on the accuracy of responding or distribution of best-fitting models
      relative to A-B training in the rule-based category learning tasks. These results
      both provide support for a multiple-systems approach to category learning in
      which one system is procedural-learning-based and argue against the validity of
      single-system approaches.

PMID- 15732709
TI  - Processing doubly quantified sentences: evidence from eye movements.
AB  - We investigated the processing of doubly quantified sentences, such as KeUy
      showed a photo to every critic, that are ambiguous as to whether the indefinite
      (a photo) specifies single or multiple referents. Ambiguity resolution requires
      the computation of relative quantifier scope: Whether a or every takes wide
      scope, thereby determining how many entities or events are to be represented. In
      an eye-tracking experiment, we manipulated quantifier order and whether
      continuations were singular or plural, for constructions with the direct or the
      indirect object occurring first. We obtained effects consistent with the on-line
      processing of relative scope at the doubly quantified phrase and considered two
      possible explanations for a preference for singular continuations to the
      quantified sentence. We conclude that relative quantifier scope is computed on
      line during reading but may not be a prerequisite for the resolution of definite
      anaphors, unless required by secondary tasks.

PMID- 15732710
TI  - [Immune disorders in erosive and ulcerative lesions to the gastroduodenal
      mucosa].

PMID- 15732711
TI  - [Conservative therapy for chronic renal failure].

PMID- 15732712
TI  - [Cerebral microcirculation and structural changes in the brain in essential
      hypertension].
AB  - The purpose of the study was to examine cerebral microcirculatory and structural
      changes in 32 patients (20 males and 12 females whose age varied from 37 to 63
      years) with moderate arterial hypertension (AH). All the patients underwent
      single-photon emission computed tomography of the brain, using (99m)Tc
      hexamethylpropyleneaminoxylfor the evaluation of perfusion, as well as magnetic
      resonance imaging for the examination of cerebral structures. Cerebral structural
      changes and perfusion impairments were detected in patients with AH, even if they
      had no clinical signs of cerebrovascular insufficiency. Inadequate blood flow
      most frequently occurred in the parietal and temporal regions of the brain. There
      was a reduction in the cerebrovascular reserve in the frontal lobes in AH.

PMID- 15732713
TI  - [Efficacy of emoxypine in combined therapy for elderly patients with postinfarct
      cardiosclerosis and heart failure].
AB  - Forty-four patients with coronary heart disease, angina pectoris, prior
      myocardial infarction, and NYHA Functional Class II-IV heart failure were
      examined. Group 1 patients received emoxypine during combined therapy (CT). Group
      2 patients took CT alone (a control group). The results of the study suggest that
      emoxypine significantly improves the clinical symptomatology and shows marked
      antianginal and antiischemic effects. As compared with the control group, Group 1
      shows a more significant hemodynamic improvement. Moreover, the inclusion of
      emoxypine into CT for elderly patients with prior myocardial infarction produces
      a normalizing effect on oxidative stress. By taking into account the foregoing,
      it should be stated that it is expedient to include emoxypine into CT for this
      category of patients.

PMID- 15732714
TI  - [Characterization of arrhythmia in pulmonary hypertension in patients with
      bronchial obstructive diseases].
AB  - To study the pattern and incidence of arrhythmias in relation to the mean
      pulmonary trunk pressure (MPTP), 24-hour SCG monitoring and Doppler pulse EchoCG
      were performed in 32 patients with chronic obstructive lung disease and in 13
      patients with bronchial asthma. The summarized results of 24-hour ECG suggest
      that the number and grades of arrhythmias increase when MPTP becomes more than 13
      mm Hg. There is a highly significant mean force correlation between MPTP and
      complicated cardiac arrhythmias (paroxysmal supraventricular tachycardia, coupled
      ventricular extrasystoles, and unsteady ventricular tachycardia). A more than 13
      mm increase in MPTP may be a predictor for the assessment of a risk of the
      existence of complicated cardiac arrhythmias on an exacerbation of bronchial
      obstructive lung diseases.

PMID- 15732715
TI  - [Clinical and instrumental evaluation of the myocardial reserve in patients with
      prior myocardial infarction].
AB  - The clinical manifestations of heart failure (HF), myocardial systolic and
      diastolic functions and the indices of remodeling of the left ventricle (L V)
      were compared to define the most informative characteristics of the myocardial
      reserve (MR) in patients with prior myocardial infarction (MI). Examination of
      220 patients with MI indicated that the low LV ejection fraction reliably
      determined only a high functional class (FC) of HF. Myocardial diastolic
      dysfunction (DD) was equally characteristic of any FCs of HF and the restrictive
      type of blood filling was most commonly associated with FC III-IV of HF. LV
      concentric hypertrophy, as well as DD, occurred in all FCs of HF. The detection
      rate of LV eccentric remodeling significantly increased from 5.1% in FC I to
      98.7% in FC IV, which characterized this process as the most characteristic while
      grading the decrease in MR in patients with MI.

PMID- 15732716
TI  - [Circadian blood pressure profile in patients with metabolic syndrome and
      osteoarthrosis during therapy with nonsteroidal anti-inflammatory drugs].
AB  - Twenty-three patients with metabolic syndrome (MS) concurrent with ostearthrosis
      (OA) who had been long taking various nonsteroidal anti-inflammatory drugs
      (NSAID) (a study group) and 23 patients with MS without locomotor diseases (a
      control group) were examined. The groups were matched by gender, age, body mass
      index, and office blood pressure values. All the patients underwent 24-hour blood
      pressure (BP) monitoring. The mean 24-hour, mean diurnal and nocturnal variables
      of BP and the proportion of non-dippers were estimated in the study and control
      groups. In the study group, there were higher levels of the mean 24-hour systolic
      BP (SBP) (p = 0.044), pulse BP (p = 0.023), mean diurnal and mean nocturnal SBP
      (p = 0.040 and 0.036, respectively). There was also a predominance of non-dippers
      in the study group as compared with the control one (p = 0.037). Thus, the use of
      NSAID in patients with MS and concomitant OA causes negative changes in the 24
      hour profile of BP.

PMID- 15732717
TI  - [Trends of mental and somatic diseases during therapy of endemic goiter].
AB  - The trend of mental and somatic diseases was studied in 70 patients with epidemic
      goiter (EG) treated with L-thyroxine or iodides during 1-5-year follow-up.
      Borderline mental disorders (diminished memory and attention, emotional and
      intellectual disorders) were found to be stable in these patients. The most
      delicate functions of the brain, such as the capacity for analysis and synthesis,
      are particularly vulnerable. Irrespective of the age of a patient, his/her
      educational level, occupation, the size of goiter, concrete rather than abstract
      logic thinking are prevalent in patients with EG. Drug treatment of EG only
      improves the patients' health status, but fails to eliminate evolving mental
      disorders even if the sizes of the thyroid can be brought to the normal values,
      the use of L-thyroxine is more effective that that of iodides.

PMID- 15732718
TI  - [The specific features of thyrotoxicosis and euthyroid hyperthyroxinemia
      developed due to the use of cordarone].
AB  - Thyrotoxicosis (TT) is one of the thyroid (T) dysfunctions occurring with the use
      of cordarone. The clinical features of TT were studied in cordarone-treated
      patients living in Moscow and its regions (mild and moderate iodine deficiency
      regions). The patients were examined by using currently available procedures for
      measuring thyroid-stimulating hormone, free thyroxine, free triiodothyronine,
      antibodies to TH, TPO, interleukin-6 (IL-6), and C-reactive protein (CRP), and by
      employing T ultrasound study, Holter ECG monitoring. TT was ascertained to
      develop in the presence of both the pathologically altered (16/23, 69%) and
      intact T (7/23, 31%). Examining the course of cardiac arrhythmias (CA) in
      developed TT has established that this condition gives rise to their recurrence.
      As compared with the control group, the patients with TT were not found to have
      higher levels of IL-6 and CRP (p > 0.05; Mann-Whitney test). Therapy with
      thyrostatic agents alone or in combination with glucocorticosteroids normalizes
      the levels of thyroid hormonesfollowing, on the average, 2-3 months. Euthyroid
      hyperthyxinemia (EHT) is frequently recorded with the use of cordarone.
      Examination of 20 patients with EHT has revealed organic pathology in 13 (65%)
      patients and its absence in 7 (35%). Recurrences of prior CA have not been found
      in EHT (p < 0.05; McNemar test). The confidence interval for the difference of
      relative frequencies of signs did not include 0). Thus, TT is a condition that
      leads to the fact that cordarone loses its antiarrhythmic effects and TT requires
      compulsory treatment. If required, therapy should be performed during the
      continued administration of the drug. EHT is not thyrotoxicosis, which is to be
      followed up.

PMID- 15732719
TI  - [Effect of the phytohepatoprotective agent maxar on the hepatic morphofunctional
      status in patients with chronic hepatitis].
AB  - The paper provides evidence for that as compared with the well-known drug carsil,
      the new Russian phytohepatoprotective agent maxar has a therapeutic efficiency in
      patients with mild and moderate chronic hepatitis (CH) of viral and alcoholic
      etiology. Maxar has been found to produce a more pronounced hepatoprotective
      effect, to a greater extent, in CH of alcoholic etiology.

PMID- 15732720
TI  - [Antihypertensive and antiischemic effectiveness and safety of the AT1-receptor
      blocker irbesartranin arterial hypertension in patients with prior myocardial
      infarction].
AB  - Thirty males with prior myocardial infarction concurrent with arterial
      hypertension (AH) were examined to study the antihypertensive and antiischemic
      effects of the AT1-receptor blocker irbesartran. Group 1 comprised 12 (40%)
      patients with mild AH; Group 2 included 18 (60%) with moderate AH. In Group 2,
      the standard therapy with irbesartan in a single dose of 150 mg in the morning
      was supplemented by the beta1-adrenoblocker atenolol in the average daily dose of
      31.25 mg. In Group 1 patients there were decreases in systolic blood pressure
      (SBP) by 28% and diastolic blood pressure (DBA) by 19% while in Group 2 receiving
      combined therapy with atenolol, SBP lowered on the average of 38.3 mm Hg of the
      baseline values and DBA became normal in 66.7% of the patients (p < 0.00). Thus,
      irbesartan provides good antihypertensive and antiischemic effects in patients
      with grade 1 AH; the combined therapy enhances the efficiency of treatment by 92%
      in patients with moderate AH.

PMID- 15732721
TI  - [The effectiveness and safety of nimesulide (nimesile) in patients with gouty
      arthritis].
AB  - Patients with gout are at a high risk for drug-induced complications associated
      with the use of nonsteroidal anti-inflammatory drugs due to the baseline renal
      and hepatic abnormalities, metabolic disturbances, and concomitant diseases, such
      as arterial hypertension or type 2 diabetes mellitus. In this connection, it is
      expedient to use safer selective cycloxygenase-2 (COG-2) inhibitors. However,
      there are only single reports dealing with studies of the effectiveness and
      safety of selective COG-2 inhibitors in gout. The study was undertaken to
      evaluate the effectiveness and safety of the selective COG-2 inhibitor nimesulide
      (nimesile) in acute gouty arthritis (GA). Twenty male patients (whose mean age
      was 51.1 +/- 8.4 years) with PA were examined. Seven patients were found to have
      monoarthritis of 1 metatarsophalangeal joint, oligoarthritis was present in 9
      patients and 4 patients had polyarthritis. The history of arthritis was as long
      as 6 days in 16 patients and 21-30 days in 4. Nimesulide was given in a dose of
      200 mg/day for at least 14 days. The time course of changes in the objective and
      subjective symptoms of arthritis was studied. The tolerability of the drug was
      evaluated by its effect on renal (the levels of creatinine and urea, creatinine
      clearance) and hepatic (alanine transferase (ALT), aspartate transferase (AST),
      gamma-glutamyltranspeptidase (gamma-GTP)) functions, and blood pressure (BP) [24
      hour BP monitoring (24-h BPM) before and after treatment. There were clear
      positive changes in the major parameters of arthritis: the swelling index was 4.5
      +/- 2.7 and 0.5 +/- 0.5 scores before and after treatment, respectively;
      hyperemia, 3.5 +/- 2.5 and 0.1 +/- 0. 1 scores; articular index, 3.6 +/- 2.0 and
      0.7 +/- 0.6 scores; pain (visual analogue scale) when resting, 53.8 +/- 17.6 and
      4.7 +/- 4.6 scores, and that when moving, 68.3 +/- 16.0 and 9.0 +/- 8.8 mm,
      respectively. Negative changes in the levels of creatinine and uric acid and a
      reduction in creatinine clearance were not observed. There were no increases in
      the levels of ACT, ALT, gamma-GTP. 24-h BPM did not reveal any significant
      changes in the mean 24-hour, mean diurnal and nocturnal variables of BP. The 24
      hour BP profile became better in some patients. Thus, nimesulide is an effective
      and safe drug for the treatment of PA.

PMID- 15732722
TI  - [Use of meloxicam (movalis) in patients with rheumatic diseases with concomitant
      coronary heart disease].
AB  - The purpose of the study was to examine the clinical features of the course of
      coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) and to
      evaluate the effects of the selective cyclooxygenase-2 (COG-2) inhibitor movalis
      (meloxicam) in two dosage forms (as injections and tablets) on the course of CHD
      in this group of patients. The developed questionnaire was used to make a
      comparative screening survey of 304 patients with RA and 152 patients with
      osteoarthrosis (OA), who were aged above 40 years. A comprehensive examination of
      the cardiovascular system was performed in 52 patients with RA concurrent with
      CHD and 25 patients with OA concurrent with CHD. Angina pectoris on exertion was
      detected in 37% of the patients with PA and in 35% of the patients with OA. Most
      (52%) patients with RA and CHD reported rare anginal attacks (once a month)
      whereas 24-day ECG monitoring revealed myocardial ischemia in 71% of the patients
      with RA concurrent with CHD; only silent ischemic episodes were recorded in 70%
      of them. The incidence of silent myocardial ischemia was higher in patients with
      RA concurrent with CHD than that in those with OA concurrent with CHD (p < 0.03).
      Examination of the incidence of anginal attacks showed that there was a tendency
      of the incidence of pains to decrease in patients with RA concurrent with CHD who
      took selective COG-2 inhibitors. Patients with RA concurrent with CHD who
      received movalis had atendency of arrhythmia to occur more rarely and of the
      duration of myocardial ischemia to reduce as compared with those who took
      nonselective COG-2 inhibitors.

PMID- 15732723
TI  - [Use of somatulin in clinical practice].

PMID- 15732724
TI  - [A case of thoracic aortic aneuysmal rupture with pulmonary hemorrhage].

PMID- 15732725
TI  - [Potentialities of development of multiple diskoid atelectases in acute purulent
      bronchitis].

PMID- 15732727
TI  - The FCTC enters into effect in 2005.

PMID- 15732726
TI  - [Study of the training of therapist in terms of educational standards].

PMID- 15732728
TI  - Selman Abraham Waksman and the discovery of streptomycin.

PMID- 15732729
TI  - Tuberculosis deaths in countries with high HIV prevalence: what is their use as
      an indicator in tuberculosis programme monitoring and epidemiological
      surveillance?
AB  - Although the reduction of tuberculosis deaths is one of the aims of tuberculosis
      control, it has not always been a priority for National Tuberculosis Programmes
      (NTPs). The usual explanation is that death as a treatment outcome not associated
      with ongoing tuberculosis transmission is not relevant to the public health
      objective of cutting the cycle of disease transmission. However, death as an
      adverse outcome for tuberculosis patients and their families is an important
      indicator in NTP monitoring. Global health targets agreed as part of the
      Millennium Development Goals include the reduction of tuberculosis deaths.
      Tuberculosis deaths as an indicator of the impact of tuberculosis control
      measures are therefore important in the epidemiological surveillance of progress
      towards these targets. These considerations are particularly important in
      countries with high human immunodeficiency virus (HIV) prevalence where HIV has
      exacerbated the tuberculosis epidemic and is now the single best predictor of
      tuberculosis incidence. Tuberculosis deaths are also closely linked to HIV
      prevalence. Routine NTP data on tuberculosis cohort deaths are important in
      programme monitoring, and improvements in recording and reporting of deaths would
      help to overcome limitations in their accuracy. As routine NTP data on
      tuberculosis cohort deaths are insufficient as an indicator in epidemiological
      surveillance regarding the impact of NTPs on tuberculosis mortality, measuring
      progress towards targets for reduced tuberculosis deaths depends on improved
      national vital registration systems for a more accurate determination of
      tuberculosis mortality.

PMID- 15732730
TI  - Human resources for control of tuberculosis and HIV-associated tuberculosis.
AB  - The global targets for tuberculosis (TB) control were postponed from 2000 to
      2005, but on current evidence a further postponement may be necessary. Of the
      constraints preventing these targets being met, the primary one appears to be the
      lack of adequately trained and qualified staff. This paper outlines: 1) the human
      resources and skills for global TB and human immunodeficiency virus (HIV) TB
      control, including the human resources for implementing the DOTS strategy, the
      additional human resources for implementing joint HIV-TB control strategies and
      what is known about human resource gaps at global level; 2) the attempts to
      quantify human resource gaps by focusing on a small country in sub-Saharan
      Africa, Malawi; and 3) the main constraints to human resources and their possible
      solutions, under six main headings: human resource planning; production of human
      resources; distribution of the work-force; motivation and staff retention;
      quality of existing staff; and the effect of HIV/AIDS. We recommend an urgent
      shift in thinking about the human resource paradigm, and exhort international
      policy makers and the donor community to make a concerted effort to bridge the
      current gaps by investing for real change.

PMID- 15732731
TI  - Performance-related allowances within the Malawi National Tuberculosis Control
      Programme.
AB  - SETTING: National Tuberculosis (TB) Control Programme (NTP), Malawi. OBJECTIVES:
      To determine the feasibility and effectiveness of performance-related allowances
      for NTP personnel working at central and regional levels in Malawi. In
      particular, to determine 1) whether programme staff can complete 6-monthly self
      assessment forms related to the tasks they are expected to perform during that
      period, and 2) whether the NTP can achieve four key programme targets related to
      case finding, treatment outcome and the sending of sputum specimens for drug
      resistance monitoring. DESIGN: A descriptive study. RESULTS: For January to June
      2003, 25 personnel completed self-assessment forms, and in all cases individual
      performance was judged satisfactory. For July to December 2003, 21 personnel
      completed self-assessment forms, and in 20 cases individual performance was
      judged satisfactory. In the first quarter of 2003, only one target was achieved
      for the country, and NTP personnel were awarded one quarter of the performance
      payment. In the third quarter, two targets were achieved and NTP personnel were
      awarded one half of the performance payment. CONCLUSION: It is feasible to
      implement performance-related payments for NTP personnel. Ways to routinely
      introduce such a system for NTP and other staff in the health sector urgently
      need to be explored.

PMID- 15732732
TI  - Capacity building for international tuberculosis control through operations
      research training.
AB  - SETTING: In resource-poor countries, few tuberculosis (TB) program staff at the
      national, provincial, and even district levels have the basic analytical and
      epidemiological skills necessary for collecting and analyzing quality data
      pertaining to national TB control program (NTP) improvements. This includes
      setting program priorities, operations planning, and implementing and evaluating
      program activities. OBJECTIVES: To present a model course for building capacity
      in basic epidemiology and operations research (OR). DESIGN: A combination of
      didactic lectures and applied field exercises were used to achieve the main
      objectives of the 6-day OR course. These were to increase the understanding of
      quantitative and qualitative research concepts, study design, and analytic
      methods, and to increase awareness of how these methods apply to the epidemiology
      and control of TB; and to demonstrate the potential uses of OR in answering
      practical questions on NTP effectiveness. As a final outcome, course participants
      develop OR proposals that are funded and later implemented. RESULTS: Since 1997,
      this OR course has been conducted nine times in five countries; 149 key NTP and
      laboratory staff have been trained in OR methods, and 44 OR protocols have been
      completed or are underway. CONCLUSION: This low-cost model course can be adapted
      to a wide range of public health issues.

PMID- 15732733
TI  - Establishment and development of the National Tuberculosis Control Programme in
      Vietnam.
AB  - OBJECTIVE: To describe the establishment and development of the National
      Tuberculosis Control Programme (NTP) of Vietnam. METHODS: Data were obtained from
      the surveillance system established by the new NTP in 1986 and based on the
      principles now described as the WHO DOTS strategy. RESULTS: The proportion of
      districts covered by the NTP increased from 40% in 1986 to almost 100% in 2000.
      The proportion of communes applying NTP guidelines increased from 18% in 1986 to
      99.8% in 2000. The total number of tuberculosis cases notified increased from
      8737 in 1986 to 89 792 in 2000. Most of these are new smear-positive cases. Based
      on WHO estimations of the incidence rate, the proportion of new smear-positive
      cases detected and put on short-course treatment has been over 70% since 1996.
      Reported cure rates with short-course chemotherapy are consistently over 85%.
      CONCLUSIONS: DOTS is feasible in a low-income, high-burden country. The main
      reasons for success were political commitment, a well-functioning health network,
      integration of tuberculosis control into the general health service at district
      level, a continuous supply of drugs and effective external support. Major
      challenges are long-term financial support, expansion to remote areas and
      vulnerable groups, definition of the role of the private sector, and future
      developments of the HIV epidemic and multidrug resistance.

PMID- 15732734
TI  - Results of tuberculosis screening in applicants for migration in Vietnam and
      Cambodia.
AB  - SETTING: Pre-migration medical screening programmes in Ho Chi Minh City, Vietnam
      and Phnom Penh, Cambodia. OBJECTIVE: To compare the rates of newly diagnosed
      bacteriologically confirmed tuberculosis (TB) in a cohort of migration applicants
      in Vietnam and Cambodia with current estimates of the TB burden in these
      countries. DESIGN: Interviews and medical screening of 5108 Vietnamese and 910
      Cambodian migration applicants who applied for an Australian visa. RESULTS: On
      initial testing, the rate of bacteriologically confirmed TB among the Vietnamese
      cohort was 157 per 100,000 population compared to 989/100,000 among the Cambodian
      cohort. When cases detected during follow-up testing were included, the rate in
      the Vietnamese cohort was 489/100,000 compared to 1209/100,000 in the Cambodian
      cohort. CONCLUSIONS: Although it has been suggested that the rate of newly
      diagnosed bacteriologically confirmed TB among migration applicants would
      underestimate the prevalence of TB in the Vietnamese and Cambodian populations,
      the rates found were substantially higher than current point estimates of the
      prevalence of TB, particularly for Vietnam. Our findings suggest that current
      published estimates of the tuberculosis burden in Vietnam and Cambodia may be
      conservative.

PMID- 15732735
TI  - Treatment outcome of multidrug-resistant tuberculosis among Vietnamese
      immigrants.
AB  - OBJECTIVE: To review the outcome for MDR-TB treatment among potential migrants
      from Vietnam. SETTING: All cases of documented MDR-TB treated by the
      International Organization of Migration (IOM) in Vietnam from 1989 to 2000 were
      reviewed. METHODS: MDR-TB was defined as isoniazid- and rifampicin-resistant
      Mycobacterium tuberculosis. All cases of TB treated by the IOM and recorded in
      the computerised database were reviewed to identify MDR-TB cases. Demographics,
      chest radiograph results, drug resistance, drug use and dosage, duration of
      treatment, and outcome were analysed. RESULTS: Forty-four cases of MDR-TB were
      identified. Treatment consisted of ambulatory directly observed treatment with an
      8-drug protocol: isoniazid, rifampicin, pyrazinamide, ethambutol, capreomycin,
      ethionamide, ofloxacin and cycloserine. This initial protocol was modified due to
      drug availability or drug intolerance. Patients were treated with a median of 8
      drugs (range 6-12). Mean duration of treatment for MDR-TB was 23.0 (SD+/-11.4)
      months. Thirty-eight (86%) patients were cured and emigrated, one failed
      treatment (2%), three were lost to follow-up (7%) and two died (4%). CONCLUSION:
      Treatment for MDR-TB provided by the IOM was effective in preparing a low-income
      population for migration.

PMID- 15732736
TI  - High prevalence of drug-resistant tuberculosis, Republic of Lithuania, 2002.
AB  - BACKGROUND: Nations of the former Soviet Union have the world's highest reported
      levels of resistance to anti-tuberculosis drugs. We conducted the first national
      survey of anti-tuberculosis drug resistance in the Republic of Lithuania.
      METHODS: We tested Mycobacterium tuberculosis isolates from all incident culture
      positive pulmonary TB patients registered in 2002. New patients were those
      treated for <1 month with any first-line anti-tuberculosis drug (isoniazid [INH],
      rifampin [RMP], ethambutol, or streptomycin); previously treated patients were
      those treated for > or =1 month. RESULTS: Of 1163 isolates, 475 (41%) were
      resistant to at least one first-line drug, and 263 (23%) were resistant to at
      least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and
      187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly
      selected for extended testing at an international reference laboratory, 27 (51%,
      95%CI 38-66) had resistance to pyrazinamide, 21 (40%, 95%CI 27-55) to kanamycin,
      and 9 (17%, 95%CI 8-30) to ofloxacin. CONCLUSIONS: The prevalence of MDR-TB in
      Lithuania is among the world's highest. Among MDR-TB isolates, aminoglycoside and
      fluoroquinolone resistance were common. To combat drug-resistant TB, Lithuania
      has implemented the WHO global TB control strategy (DOTS), and is developing an
      MDR-TB treatment program (DOTS-Plus).

PMID- 15732737
TI  - Drug resistance profiles of Mycobacterium tuberculosis isolates: five years'
      experience and insight into treatment strategies for MDR-TB in Lima, Peru.
AB  - SETTING: Lima, Peru. OBJECTIVE: To describe drug resistance profiles of TB
      isolates from patients at risk for multidrug-resistant tuberculosis (MDR-TB), and
      to consider the implications of these findings for treatment. DESIGN: Descriptive
      study of drug susceptibility testing (DST) results for TB isolates from 1680
      patients referred for suspicion of MDR-TB between 1996 and 2001. RESULTS: Of 1680
      isolates tested, 1144 (68%) were resistant to at least one anti-tuberculosis drug
      and 926 (55%) were MDR-TB strains. Of 926 MDR isolates, 50 (5%) were resistant to
      INH and RMP alone, while 367 (40%) were resistant to at least five first-line
      drugs. We identified 146 unique drug resistance profiles, the most common of
      which accounted for 11% of drug-resistant isolates. The annual prevalence of
      isolates with resistance to at least five first-line drugs rose significantly
      during the study period, from 29% to 37% (P = 0.00086). CONCLUSIONS: This is a
      group of patients with TB disease among whom the prevalence of a broad spectrum
      of often highly drug-resistant strains appears to be increasing over time. A
      single standardized retreatment regimen may be inadequate to cure most patients.
      Capacity for drug sensitivity testing is essential for development of multiple
      standardized retreatment or individualized treatment regimens and epidemiological
      surveillance for planning.

PMID- 15732738
TI  - Use of fluorescence resonance energy transfer for rapid detection of isoniazid
      resistance in Mycobacterium tuberculosis clinical isolates.
AB  - SETTING: Rapid detection of drug resistance in Mycobacterium tuberculosis is
      important to select effective treatment and prevent transmission of resistant
      isolates. OBJECTIVE: To evaluate the use of fluorescence resonance energy
      transfer (FRET) for rapid detection of isoniazid (INH) resistance in M.
      tuberculosis clinical isolates. DESIGN: One hundred INH-resistant and 50 INH
      susceptible isolates of M. tuberculosis were included in the study. The drug
      susceptibility of all isolates was determined by the standard agar proportion
      method, and all isolates were then tested by FRET. Three genes associated with
      INH resistance, katG, inhA and ahpC, were analysed. All isolates were amplified
      with three pairs of primers. Three pairs of fluorescently labelled DNA probes
      specific to codon 315 of katG, nucleotide 209 in the regulatory region of inhA
      and a frequent mutation site in the intergenic region of oxyR-ahpC, were used for
      mutation detection. RESULTS: The results obtained using FRET were compared with
      those from the proportion method. The sensitivity and specificity of FRET were
      respectively 76% and 100%. The frequencies of mutations were 48% in katG, 17% in
      inhA, 8% in ahpC, 2% in inhA-ahpC and 1% in inhA-katG. CONCLUSION: FRET is a
      rapid, specific method that can be useful to detect INH resistance in M.
      tuberculosis clinical isolates.

PMID- 15732739
TI  - Prevalence of tuberculous lymphadenitis in children in Wardha district,
      Maharashtra State, India.
AB  - SETTING: Rural area of Wardha district, Maharashtra State, Central India.
      OBJECTIVE: To determine the prevalence of tuberculous lymphadenitis in children
      aged 0-14 years in the study area and to assess factors that may contribute
      towards the prevalence. DESIGN: House to house survey of a population of 23,229
      in 35 neighbouring villages with 7900 children aged 0-14 years from May 1993 to
      May 1994 and from March 1995 to February 1996. RESULTS: The prevalence of
      tuberculous lymphadenitis/1000 children was 4.43. The maximum prevalence was in
      the 5-9 years age group. The prevalence was 34 times higher in children with
      positive family history of tuberculosis than in those without a history. There
      was an association between prevalence and the living standards of the children,
      with a higher prevalence in families that belonged to an underprivileged social
      class living in thatched, improvised houses. Multiple cervical lymph nodes >2 cm
      and with matting and fluctuation were found to be characteristic clinical
      features. CONCLUSION: The prevalence of peripheral lymphadenopathy was 27.2/1000
      children and that of tuberculous lymphadenitis was 4.43/1000. Positive history of
      contact in the family was a significant epidemiological indicator of tuberculous
      glands.

PMID- 15732741
TI  - Temperature affects the results of the glutaraldehyde test in the diagnosis of
      pulmonary tuberculosis.
AB  - SETTING: Subjects attending the District Tuberculosis Clinic and a Teaching
      Hospital in Jodhpur were studied at the Desert Medicine Research Centre, Jodhpur.
      OBJECTIVES: To confirm the effect of temperature on the results of the blood
      glutaraldehyde test (GT) and to examine the sensitivity and specificity of the
      restandardised test procedure. DESIGN: Blood glutaraldehyde gelification time
      (BGGT) was compared, in the same blood samples, at 19, 22 and 25 degrees C and
      after storage at 1) room temperature and at 2) 2-8 degrees C for 3-5 h, using the
      paired t-test. After restandardisation of the procedure, the GT was carried out
      on 88 sputum culture-positive cases with pulmonary tuberculosis (PTB) and 182
      controls. The technician was blinded to patient information. RESULTS: BGGT
      significantly varied with the temperature of the water bath and the temperature
      at which blood samples were stored before testing. When the test was carried out
      in the water bath at 22 degrees C after storing blood for 3-5 h at 2-8 degrees C,
      as per the restandardised procedure, the specificity of GT was 96.2% (95 %CI
      93.36-98.95) and the sensitivity was 84.1% (95%CI 76.45-91.73). CONCLUSION:
      Restandardised GT is a reliable, simple, easy, rapid, inexpensive and user
      friendly test for diagnosis of PTB which does not require sophisticated
      laboratory equipment.

PMID- 15732740
TI  - Increased detection by restaining of acid-fast bacilli in sputum samples
      transported in cetylpyridinium chloride solution.
AB  - SETTING: Seventeen health facilities in a Tuberculosis Unit, and the Tuberculosis
      Research Centre (TRC), Chennai, India. AIM: Evaluation of restaining by the
      auramine-phenol method for detection of acid-fast bacilli (AFB) in direct smears
      of samples transported in cetylpyridinium chloride (CPC) solution. METHODS: Among
      patients attending the above health facilities, 730 samples were collected in CPC
      and transported to the TRC. Two direct smears were prepared from each sample, one
      stained by the usual auraminephenol method (primary staining) and the other
      stained again by the same method (restaining) for examination by fluorescence
      microscopy. All the samples were processed for culture of Mycobacterium
      tuberculosis. RESULTS: A significantly higher proportion (49.6%) of samples were
      positive by restaining compared to primary staining (32.5%, P < 0.0001). Of 362
      samples positive by restaining, 38.7% were negative by primary staining. The
      yield of different grades of smears was significantly higher with restaining than
      with primary staining (P < 0.0001). More smear-negative culture-positive smears
      were observed with the primary than with the restaining method (178/400 [44.5%]
      vs. 78/ 400 [19.5%], P < 0.001). CONCLUSION: The rate of detection of AFB in
      direct smears made from sputum samples transported in CPC was higher on
      restaining than on primary staining.

PMID- 15732742
TI  - Evaluation of a rapid differentiation test for the Mycobacterium tuberculosis
      complex by selective inhibition with rho-nitrobenzoic acid and thiophene-2
      carboxylic acid hydrazide.
AB  - SETTING: Mycobacterial growth in media to which inhibitory substances are added
      has been used in species identification. Growth of the Mycobacterium tuberculosis
      complex (MTC) is inhibited by rho-nitrobenzoic acid (PNB), whereas non
      tuberculous mycobacteria (NTM) are resistant. Thiophene-2-carboxylic acid
      hydrazide (TCH) is useful in the differentiation of MTC when performed together
      with other tests. OBJECTIVE: To develop a test using PNB or TCH added to culture
      medium, and to evaluate its usefulness in the screening of mycobacteria isolates.
      DESIGN: In 2001, PNB testing was performed in 109 M. tuberculosis strains
      identified by Instituto Adolfo Lutz (IAL) and 52 NTM strains from the institute's
      culture collection. The drugs were added to Lowenstein-Jensen (LJ) medium and to
      BBL-MGIT. RESULTS: Species differentiation of MTC with the MGIT/TCH method was
      similar to that observed using the conventional LJ/TCH method. The accuracy of
      the MGIT/PNB method to differentiate NTM and MTC strains was 99.4%. The BBL-MGIT
      system allowed presumptive identification in 3-11 days, compared to > or =12 days
      with LJ medium. CONCLUSION: A simple, low-cost test using growth inhibitors may
      be incorporated into a modern, safe and quick methodology enabling
      differentiation of MTC and NTM.

PMID- 15732743
TI  - What can be learnt from tobacco butts? An observational study in a realistic
      hospital setting.
AB  - OBJECTIVE: Examination of tobacco butts and its possible use in tobacco control.
      DESIGN: Macroscopic examination of cigarette butts collected outside or in
      dedicated smoking rooms of a smoke-free hospital. RESULTS: Of 925 butts, 3.8%
      were cigarillos, 11.1% cigarettes without filter, 57.7% ventilated filter
      cigarettes, 22.5% filter cigarettes without macroscopic ventilation and 4.9%
      undetermined. Thirty-six different cigarette brands were identified. A wide
      distribution of butt lengths (mean 32.1 mm, variation coefficient 28%),
      peripheral ovalisation of the filter in 83.9%, and extended browning of the mouth
      end of the filter in 48.6% were observed. Vent holes were macroscopically
      detectable in 70.5% and a sharp decrease in browning in 53.4% of the filter
      cigarettes. Most (94.7%) ventilation holes were located at > or =10 mm from the
      mouth end. CONCLUSIONS: In a smoke-free hospital, the use of tobacco products
      (mainly ventilated filter cigarettes) remains sizeable. Given the wide
      distribution of butt lengths, the number of cigarettes per day is a poor marker
      of toxin intake. Vent-hole localisation and signs of vent-blocking confirm the
      inadequacy of machine-measured smoke yields and the presence of compensatory
      smoking. More intensive individual cessation advice with pharmacological support
      is necessary. Examination of a smoker's own cigarette butts can be used as a tool
      for individual cessation advice.

PMID- 15732744
TI  - Second-line drug susceptibilities of Thai multidrug-resistant Mycobacterium
      tuberculosis isolates.
AB  - The emergence of multidrug-resistant tuberculosis (MDR-TB) is increasing and is
      exacerbated by the human immunodeficiency virus (HIV) epidemic. The standard
      short-course regimen used for the treatment of tuberculosis is likely to be
      ineffective against MDR-TB, leading to the need for second-line drugs. In such
      situations, drug susceptibility testing (DST) is necessary to select an
      appropriate treatment regimen. In this study, DST of 99 MDR-TB strains isolated
      in Thailand was performed using a drug-impregnated disc method. The results
      showed that 94.95% of the strains were susceptible to amikacin and kanamycin,
      90.91% to ciprofloxacin and ofloxacin, 85.86% to para-aminosalicylic acid, and
      78.79% to ethionamide.

PMID- 15732745
TI  - Diagnostic yield of peripheral lymph node needle-core biopsies in HIV-infected
      adults with suspected smear-negative tuberculosis.
AB  - Significant lymphadenopathy in human immunodeficiency virus (HIV) infected adults
      in developing countries is usually caused by tuberculosis. We studied the safety
      and diagnostic yield of needle-core biopsies, under local anaesthetic, of
      enlarged lymph nodes in 26 HIV-infected adults presenting with suspected
      tuberculosis who were sputum smear-negative. Biopsy samples were sent for
      histology and mycobacterial culture. Induced sputum, urine and blood were also
      sent for mycobacterial culture. The procedure was well tolerated. A definitive
      diagnosis was made on initial needle-core biopsy in 22 subjects (85%) and in two
      of three subjects who underwent a second needle-core biopsy. Tuberculosis was the
      final diagnosis in 24 subjects (92%).

PMID- 15732746
TI  - Storage of heat-fixed unstained sputum AFB smears for panel testing in a
      tuberculosis unit in South India.
AB  - To evaluate the suitability for panel testing of heat-fixed unstained sputum AFB
      smears stored for up to 10 months, panels of slides were prepared at the national
      laboratory and stored under ambient conditions. Every month, three slides were
      utilised for panel testing in each of 12 microscopy centres; 70 smears were
      checked in a blinded fashion after 10 months. Reading errors occurred in 15/360
      slides used in panel testing and in 4/70 slides used in blinded checking. The
      quality and grading of heat-fixed unstained smears were unaffected for up to 10
      months and were found suitable for panel testing.

PMID- 15732747
TI  - Comparison of variants of carbol-fuchsin solution in Ziehl-Neelsen for detection
      of acid-fast bacilli.
AB  - To evaluate Ziehl-Neelsen (ZN) staining using variants of carbol-fuchsin
      solution, duplicate smears from 416 samples were stained with ZN, one set with 1%
      basic fuchsin and the other 0.3%. Another set of duplicate smears from 398
      samples were stained with ZN, one with 1% basic fuchsin and the other 0.1%. The
      coded smears were read and discrepancies resolved. All samples underwent
      mycobacterial culture. The sensitivity of ZN using 0.3% (65%) and 1% basic
      fuchsin (62%) was comparable, while it was reduced using 0.1% (74%) compared to
      1% basic fuchsin (83%). Reducing the concentration of basic fuchsin below 0.3% in
      ZN staining was found to significantly reduce its sensitivity.

PMID- 15732748
TI  - Completing tuberculosis prophylaxis in jail: targeting treatment and a comparison
      of rifampin/pyrazinamide with isoniazid regimens.

PMID- 15732749
TI  - Should isoniazid and clofazimine be used to treat multidrug-resistant
      tuberculosis?

PMID- 15732750
TI  - Sutton's law.

PMID- 15732751
TI  - Immigration rights, human rights and medicine.

PMID- 15732752
TI  - Vaccine preventable diseases and vaccination coverage in Australia 2001 to 2002.

PMID- 15732753
TI  - [Electrical responses of intact aortic endothelium in rats with experimental
      diabetes].
AB  - The changes in electrical properties of intact aortic endothelial cells from
      streptozotocin-induced diabetic rats were investigated. The mean resting membrane
      potential of unstimulated endothelium was significantly less negative (-32.7 +/-
      0.8 mV) as compared with the aged-matched control group (-41.2 +/- 0.9 MB). In
      diabetic rat aortic strips, acetylcholine (2 microM) hyperpolarized endothelial
      cells to -57.6 +/- 1.1 mV, whereas in control group the hyperpolarization reached
      -64.4 +/- 0.9 mV. The amplitude of the hyperpolarization in diabetic rats,
      however, was not significantly different from the control group (24.9 +/- 1.1 mV
      and 23.2 +/- 0.9 mV, respectively). It was concluded that endothelial cells of
      diabetic rat aorta have less negative membrane potential values at rest and
      during acetylcholine stimulation that may partially account for the suppressed
      endothelium-dependent relaxation in streptozotocin-induced diabetic rats.

PMID- 15732754
TI  - [Inhibitors of arginase pathway in L-arginine metabolism as a new class of
      antihypertensive drugs: action of urea on oxidative and nonoxidative metabolism
      of L-arginine and vascular tone in chronic hypertension].
AB  - It has been studied an action of chronic urea introduction (40 mg/kg, 14 and 28
      days) as arginase inhibitor on nonoxidative (arginase activity, urea, polyamines
      content) and oxidative (NOS activity, nitrite- and nitrate-anion content)
      metabolism of L-arginine in aorta, heart, plasma and erythrocytes of SHR. It has
      been shown that urea is an inhibitor of not arginase only, but also
      ornitinedecarboxilase (ODK) reactions, limiting L-arginine consumption for urea
      and polyamines synthesis and thus facilitating its utilization for nitric oxide
      synthesis by NOS. These exogenous effects of urea are not accompanied by
      amelioration of tissue ischaemization within cardiovascular system. It has been
      shown that exogenous urea down regulate blood pressure without any normalization
      of endothelim-dependent reactions of smooth muscle cells on acetylcholine in SHR.

PMID- 15732755
TI  - [Effect of modification in cell membrane fatty acid composition on adrenergic
      cardiac and vascular reactivity].
AB  - The work is dedicated to examination of the effect an omega-3 polyunsaturated
      fatty acids (PUFA) on vascular and cardiac reactivity in intact animals. In
      experiments on isolated perfused rat hearts and isolated rings of rat aorta it
      was shown that reactivity in rats with modified membranes was lesser than in
      control animals after adding norepinephrine in raising concentrations. Use of
      omega-3 PUFA resulted in the decrease of omega-6 PUFAs (arachidonic acid (AA))
      content, while omega-3 PUFAs (EPA, DHA) content in cardiomyocytes membranes
      increased. Besides that it was shown that after omega-3 PUFA enriched diet NO3-
      content increased in cardiac tissues and blood.

PMID- 15732756
TI  - [Role of nitric oxide in the corpus cavernosum reactions evoked by hydrogen
      peroxide].
AB  - Corpus cavernosum smooth muscle spends the majority of its time in the contracted
      state consisting of tonic and tetanic components. Tetanic component is a result
      of superposition of phasic contrations ocuring spontaneously with a frequency of
      5-27/minute. Hydrogen peroxide (H2O2) in concentration of 10(-3) mol/l causes a
      transient increase in tetanic contraction lasting 5 to 8 minutes, followed by
      either recovery of spontaneous activity or inhibition of its frequency and muscle
      strip relaxation. 30 minutes pretreatment with the specific blocker of NO
      syntase, L-NAME, does not affect the intrinsic spontaneous activity parameters
      but enhances H2O2 evoked reaction, increasing both the amplitude and duration of
      the transient contraction by 41.2 +/- 14.5 and 52.5% +/- 22.8% (n=9)
      correspondingly. By contrast, the exogenous NO donors nitroglycerin and sodium
      nitroprusside, cause spontaneous activity inhibition and muscle strip relaxation
      resulting in the decrease of H2O2 evoked contraction and duration by 8.7 +/- 3.7
      and 24.5% +/- 10.6% (n=7) correspondingly. These results suggest that tetanic
      contraction is an important component of corpus cavernosum smooth muscle tone
      which is modulated by free radical oxygen species and controlled by NO dependent
      mechanism.

PMID- 15732757
TI  - [Effect of intermittent hypoxic training on indices of adaptation to hypoxia in
      rats during physical exertion].
AB  - The aim of this study was to investigate physical endurance, maximal oxygen
      uptake, oxygen partial pressure, and pH in blood and skeletal muscle as well as
      the muscle metabolic parameters (lactate and pyruvate concentration,
      lactate/pyruvate and NAD/NADH ratios, succinate dehydrogenase activity, ADP
      stimulated mitochondrial respiration) under various regimen of combination of
      endurance training with intermittent hypoxic training (IHT) in adult Wistar rats.
      It was shown that physical endurance, maximal oxygen uptake, and muscle PO2
      (PmO2) were maximally increased in those animals who simultaneously underwent
      endurance training and IHT. The same animals demonstrated the minimal decrease in
      PmO2, blood and muscle pH under testing intensive physical workload. The latter
      led to the lesser shifts in metabolic parameters in the muscle of rats adapted
      both to IHT and endurance training than in rats adapted to endurance training
      only. The combined effects of IHT and adaptation to load hypoxia resulted in an
      increase of the role of NADH - oxidation pathway in the mitochondrial energy
      production.

PMID- 15732758
TI  - [Heart rhythm variability in individuals with different respiration frequency].
AB  - Variability in heart rhythm and respiration frequency in the men aged 17-23 were
      measured at rest and during mental loading. It was found that the variability
      level ofcardio intervals was higher in individuals with low and high respiration
      frequency when compared with individuals with average respiration frequency at
      rest. During mental loading, the biggest changes in the amplitude of the heart
      rhythm were marked in individuals with high respiration frequency.

PMID- 15732759
TI  - [Possible role of ammonium as a paracrine regulator in the uterine tissue].
AB  - An opportunity of formation of ammonia (NH3) in utera endometrium and its
      influence on exchange of Ca2+ and H+ in plasmalemma of myometrium was
      investigated. Dissociation of endometrium stroma cells and myocytes suspension
      was carried from utera of pigs and rats in accordance with the traditional
      techniques. In suspension of stroma cells a rather high AMP-deaminase activity
      (53 +/- 2 mmol IMP/hour on 1 mg of protein) was determined. It was demonstrated
      that ammonia release in extracellular space (measured by the changes of colouring
      of trinitrobenzolsulfonate acid) was significantly amplified by 1 mM
      acetylcholine and decreased by 0,1 mM fluoride ions, nonspecific AMP-deaminase
      inhibitor. It enables to assume a role of AMP-deaminase in formation of NH3 by
      endometrium stroma cells and its release into extracellular space during
      acetylcholine stimulation. The addition of ammonia (4 mM) to suspension of
      myocytes is accompanied by significant increase in pH (measured by the change in
      BCECF fluorescence) in extracellular and intracellular space, and the last
      parameter is inhibited by the blockers of passive H+ transport across the
      membrane: 0,1 mM 4-aminopyridine and tetraethylammonium. It is possible that
      addition of ammonia-containing solution results in increase in proton gradient on
      myocyte membrane and in amplification of H+ efflux. The opportunity of
      stimulation ofacetylcholine-activated passive Ca2+ transport in myocytes by 4 mM
      NH4+ that was suppressed by 1 mM cadmium and 1 nM nifedipine was also shown using
      fluorescent probe FURA-2AM. The increase in Ca2+ concentration in cytoplasm in
      the given conditions is intensively oppressed by protonophore (0.04% 2,4
      dinitrophenol) and is effectively amplified by Na+/H+-exchange inhibitor 0,1 mM
      amyloride. It is possible to assume an amplification of lygand-activated passive
      Ca2+ transport caused by dispersion of transmembrane proton gradient which exists
      on plasmalemma and can be increased by ammonia formation in endometrium. The role
      of diffused from endometrium NH3 in regulation of utera functional activity
      requires further investigation, however already at this stage it is possible to
      assume, that NH3 molecules (or ion NH4+) can carry out a role of paracrine
      regulator in the system endometrium-myometrium.

PMID- 15732760
TI  - [Age-related excitability of the muscle after the sciatic nerve blockade in
      rats].
AB  - In adult (8 weeks) and old (24 weeks) white rats early postdenervation changes
      (in 12 and 24 hours after nerves squeezing) of bioelectric activity of
      gastrocnemius muscles were studied using electrophysiological methods. Parameters
      of the activity were: a threshold, chronaxy during direct and indirect muscle
      irritation; amplitude, duration, the latent period of action potential (AP), an
      amplitude of AP during increasing stimulation and during dual irritations. It is
      established that the changes in these parameters in group of adult animals are
      considerably more pronounced and directed to the increase in excitability of the
      denervated muscle. In the group of old animals these changes were absent or they
      were considerably smaller. It is suggested that the cause of more pronounced
      postdenervated changes in adult animals is a higher speed of axoplasmic transport
      of the substances in the motor fibers of a isciatic nerve.

PMID- 15732761
TI  - [Effect of muscle pain on c-fos expression and NADPH-diaphorase activity in the
      spinal cord].
AB  - Capsaicin (Sigma, 5 mg/l ml) was unilaterally injected into dorsal neck muscles
      (mm. trapezius, splenius) of the cat (n = 6) anesthetized with alpha-chloralose.
      The laminar distribution of Fos- immunoreactive (Fos-ir) and NADPH-d-reactive
      neurons was studied in the sections of the cervical and lumbar segments. In
      comparison to sham operated animals (n = 2), 2 h after capsaicin injection the
      significant c-fos expression was found throughout the cervical cord (C1 - C8)
      ipsilaterally and lumbar cord bilaterally (L1 - L7), while the predominant mean
      number of Fos-ir neurons was detected in the C1 - C4 and L3-L6 segments. In
      cervical spinal cord, c-fos expression was three times more than in lumbar spinal
      cord. Dorsal neck noxious stimulation produced widespread c-fos expression in the
      large and small labeled cells within lamina 1, at the neck of the dorsal horn
      (lamina V) and also in the medial part of the intermediate zone (lamina VII)
      where cells of origin of the long crossed and uncrossed descending propriospinal
      pathways to the lumbar cord were known to be localized. The main accumulations of
      NADPH-d-reactive cells were registered within the marginal zone (laminae I and
      II) and medial part of the intermediate zone (lamina VII). Fos-ir neurons were co
      distributed with NADPH-d-reactive cells within the marginal zone, and the neck of
      the dorsal horn, however, double-staining spinal neurons were not registered.
      These results strongly suggest that the revealed c-fos expression in cervical and
      lumbar segments depends on the activity of vanilloid receptors of the cervical
      muscles and confirmed the anatomical coupling of both regions through long
      propriospinal pathways which may be underlying in the cervico-lumbar nociceptive
      processing. An influence of the spino-cerebro-spinal loop on modulation c-fos
      expression in these regions is not excluded also.

PMID- 15732762
TI  - [Effect of kidney peptide preparation on the expression of lymphocyte surface
      receptors during Na+,K+-ATPase inhibition].
AB  - In the work the action of membrane-mediated kidney peptide complex on human
      periferal blood lymphocytes was studied under Na+,K+-ATPase activity inhibition.
      It was shown that ouabain pretreatment changed the functional activity of
      lymphocytes: the surface immunoglobulin expression level was decreased, antigene
      determinants CD4, CD8 expression were reduced, CD3 expression was increased
      either. The kidney peptide complex had the modulated influence on the surface
      receptors, improving the decreased CD4, CD8 and surface immunoglobulins
      expression and differently influencing the CD3 and CD72 expression. It has been
      proposed that kidney peptide complex facilitates processes of Na+,K+-ATPase
      reactivation.

PMID- 15732763
TI  - [Lipid peroxidation and activity of antioxidant enzymes in thyroidectomized
      rats].
AB  - The effect of thymalin on peroxidation of lipids in thyroidectomized rats that
      received thyroxin at a dose 2 mg/ kg was examined. It was found that 3 months
      after operation a decrease in body weight (over 2 times), weight of spleen and
      amount of cells in it took place. An increase of TB-activated products in livers
      and spleens of thyroidectomized rats 3 month later was not essential. Indices of
      enzyme activity of antioxidant system in liver were within normal ranges while
      indices of activity of catalase and superoxidedysmuthase in spleen increased by
      4,3 and 1,3 times, respectively. Simultaneous administration of thyroxin and
      thymalin promotes more effective normalization of POL peroxidation, inhibits
      development of pathologic changes in organism after removal of thyroid gland.

PMID- 15732764
TI  - [Effect of low dose of gamma-radiation on the cellular content in the center of
      chronic inflammation].
AB  - On the model of chronic aseptic carrageenan-induced inflammation in rats it is
      shown that low dose-rate y-radiation of small dose (0.1 Gy) leads to the increase
      of fibroblast and macrophage proliferation in the inflammatory focus, and
      produces considerable decrease of lymphocyte emigration at all investigated
      radiation doses. Obtained data on stimulation of proliferation in the
      inflammatory focus with possible accumulation of DNA errors at depressed
      immunological supervision by lymphocytes can indirectly point to probability of
      oncogenous potential increase in the chronic inflammatory focus at low dose-rate
      gamma-irradiation.

PMID- 15732765
TI  - [Mechanisms of adaptation to hypoxia in primary hypothyroidism].
AB  - The paper contains data concerning the stimulatory effect of subcompensated
      hypoxia on the function of thyroid gland. Hypoxia-mediated improvement of the
      state of functional respiratory system (FRS) affects the endocrine system that is
      a part of the regulatory chain of FRS. Compensation of hypoxic state that takes
      place in pathogenesis of thyroid gland hypofunction is the result of improved
      oxygen supply during adaptation to hypoxia. Optimisation of oxygen supply as the
      result of the improvement of FRS working organs leads to the increase in velocity
      of oxygen consumption by organism and can evidence about the increase of oxygen
      consumption by thyroid glands that promotes their secretory activity
      intensification.

PMID- 15732766
TI  - [Determination the individual normal values of cerebral hemodynamics in humans].
AB  - A new approach based on the adaptation and homeostasis concepts is proposed for
      determination of the individual normal value of cerebral blood circulation in
      apparently healthy humans. The homeostatic range of cerebrovascular reactivity
      was determined using hyper- and hypo- carbon dioxide functional test. Using a
      Transcranial Doppler, a mean blood flow velocity in the middle cerebral artery
      was measured. The homeostatic range limits of vasoreactivity may be considered as
      individual normal value limits of cerebral blood flow. An assessment of
      individual normal value of cerebral blood circulation allows to determine the
      operator's professional psychophysical readiness.

PMID- 15732768
TI  - [Morphofunctional changes of coccyx area in posttraumatic coccygodynia].
AB  - For definition of a pathogenesis ofposttraumatic coccygodynia, a study of morpho
      functional changes of the structures of coccyx's area was organized. The
      preparations of coccyx, removed during operative intervention from 23 different
      aged patients with manifestations of disease were analyzed by roentgen,
      histological technique and a submicroscopy. In a cartilaginous tissue from
      patients with posttraumatic coccygodynia, dystrophic changes of chondrocytes down
      to their atrophy, a destruction of the basic material with partial replacement of
      a fibrillar cartilaginous tissue with a hyaline cartilage were observed with a
      different degree of manifestation. Vessels and sacrococcygeal nervous plexus were
      subjected to pathological changes. Increased post-traumatic mobility, alterations
      in the process of ossification, deceleration of physiological joining of coccyx
      vertebras and sacrococcygeal joint alter biomechanical properties of coccyx at
      sitting. These alterations lead to the long-lasting traumatization with
      degenerative - dystrophic changes, reinforcement of pain syndrome and
      manifestation of dysfunctions of organs of pelvis.

PMID- 15732767
TI  - [Ultrastructural characteristics of lipid droplets in rat adrenocortical cells
      from zona fasciculata-reticularis].
AB  - One day cultured adrenocortical cells from zona fasciculata-reticularis were used
      in morphological experiments. The electron-microscopic and imaging analysis
      methods were used for the investigation of intracellular ultrastructure of these
      cells. Experiments which conducted in control conditions, allowed us to allocate
      three types of cells which differed by ultrastructure of the mitochondria, lipid
      droplets, smooth endoplasmic reticulum and dense bodies. It was shown that lipid
      droplets with light and homogeneous matrix, met more often in cells with
      morphological attributes of high intensity of steroidogenesis. On the contrary,
      lipid droplets, with dark matrix and a dense edging, met more often in cells
      which having morphological attributes-of low intensity of steroidogenesis.
      Ionophore A23187 or adrenocorticotropic hormone application resulted in reduction
      of lipid droplets diameter and in simultaneous increase in density of their
      arrangement in cytoplasm. At the same time droplet matrix became light and
      homogeneous in all cells. Thus, the ultrastructure of lipid droplet matrix is
      sensitive to change of calcium ions concentration in cytoplasm. Processes which
      result in change of lipid droplet ultrastructure, probably, are connected to
      steroidogenesis, nevertheless, this question requires further investigation. The
      lipid droplets" ability to form morphological contacts with smooth endoplasmic
      reticulum, mitochondria, nuclear and cellular membranes is also discussed.

PMID- 15732769
TI  - Influence of plant-originated gastroproteciive and antiulcer substances on
      gastric mucosal repair.
AB  - Fundamental basis of cellular and molecular mechanisms involved in mucosal injury
      and repair in gastrointestinal tract helps to develop new therapeutic approaches
      to various gut mucosal injury- related diseases. The study was aimed to assess
      the relations between plant-originated substances and their bioactivity measured
      in terms of antioxidant, cytoprotective and antiulceric activities and to
      deteminate if these effects are capable of affecting the gastric mucosal lesions
      induced by absolute ethanol applied intragastrically. The following plant
      originated substances were considered: Solon, capsaicin, grapefruit-seed extract
      and amaranth. The area of gastric mucosa lesions and gastric blood flow were
      measured in rats with ethanol-induced lesions without (control) and with one of
      the tested substances without and with capsaicin denervation of afferent nerves
      or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide
      synthase (NOS). MATERIAL/METHODS: male Wistar rats, weighing 180-220 g fasted for
      24 h before the study, 100% ethanol was applied ig to induced gastric lesions,
      whose area was determined by planimetry. Gastric blood flow was assessed using
      electrolytic regional blood flowmeter. RESULTS: All tested plant-originated
      substances afforded gastroprotection against ethanol-induced damage and this was
      accompanied by an increase in gastric microcirculation, both changes being
      reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment
      with L-NNA. CONCLUSIONS: Plant-originated substances are highly gastroprotective
      probably due to enhancement of the expression of NOS I, NO release and an
      increase in gastric microcirculation.

PMID- 15732770
TI  - [The application of functional magnetic resonance imaging for the assessment of
      localisation and activation of cortex smell centers depending on stimulus used in
      normal volunteers].
AB  - PURPOSE: To determine the location and activation of brain smell centres in
      response to olfactory nerve-mediated and combined olfactory and trigeminal nerve
      mediated stimulation using functional MRI. SUBJECTS AND METHODS: MRI brain scans
      were performed in 10 healthy volunteers, aged 22-36 years, right handed, non
      smokers, without any CNS diseases, not taking any medication to determine and
      compare the activated cortex regions during stimulation by patchouli and
      geraniol. fMRI was performed on Siemens Magnetom Vision 1,5 T imager with a head
      neck coil using SE and EPI sequences. Functional MR imaging studies were obteined
      in the same plane as T11 eighted images in an axial plane by using echo planar
      imaging. In each of 14 contiguous planes parallel to anterior-posterior commisure
      line images that depicted blood-oxygen-level-dependent (BOLD) effect were
      acquired. The subject inhaled odorized air through both nares for 30 seconds.
      During 30-second off period the subject received room air at the same flow rate.
      For each of activated cortical zones the number of pixels activated was
      calculated. Image reconstruction and analysis were performed using standard
      imager software installed in MR imager. RESULTS: The exposure to the olfactory
      and trigeminal nerve-mediated stimuli showed more activated regions than to the
      olfactory nerve-mediated stimuli. Geraniol evoked the biggest activation in
      orbitofrontal region, cingulate gyrus and insula. Patchouli activated
      orbitofrontal cortex, insula, parahippocampal gyrus, occipital cortex, and corpus
      callosum. CONCLUSIONS: The results of present study confirm the ability to
      localize patterns of cortical activity with fMRI during olfactory tasks.

PMID- 15732771
TI  - [Risk of postirradiation induction of cancer of the modern methods of
      radiotherapy (3D CRT and IMRT) head and neck cancer].
AB  - Ionizing radiation is a known "universal carcinogen" for a wide variety of tumors
      in man. Human populations are exposed to radiation coming from natural and
      industrial environment, and from medical sources. However, these are radiotherapy
      patients who receive the highest doses. Radiation both mutates and sterilizes
      cells (lethal effect). The risk of cancer induction from cells that have received
      very high doses of radiation (therapeutic dose about 2 Gy) is lower then from the
      cells with low doses, since the majority of them will have been sterilized. The
      epidemiological studies based on the population of atomic bomb survivors have
      indicated that the most acceptable model of carcinogenesis is the linear non
      threshold model. The evaluation of clinical risk related to a wide range of
      radiation doses, which range from 0.01 Gy to 2 Gy, is connected with many
      methodological problems such as: differences in treatment factors (dose range,
      irradiated volume, anatomical site), unknown epidemiological data (smoking abuse,
      comorbidity), shortening of the follow-up (short lifespan, migration), evaluation
      of small groups of patients. The most important difficulty is lack of the
      sufficient knowledge of genetic background which is probably most significant in
      carcinogenesis process. The introduction into clinical practice of a new
      sophisticated method of irradiation such as the three-dimensional conformal
      radiotherapy (3D CRT) or intensity modulated radiotherapy (IMRT) leads to the
      increase of low irradiation dose for very large volume of normal tissue. Thus,
      the evaluation of these new methods in the context of carcinogenesis is a very
      important objective in the future. Today, we can only introduce the most
      important questions concerned with the risk of carcinogenesis induction which
      await answers: what is the risk of induction of cancer due to the implementation
      of these new methods of treatment, and how important is this risk for clinical
      practice, especially in the case of combined radiochemotherapy? Despite a large
      body of experimental and clinical studies, radiation carcinogenesis is not fully
      understood yet. Additional problems related to the impact of irradiation of low
      dose on carcinogenesis are not resolved. For example, the bystander effect, the
      low dose hypersensitivity and the adaptive response could modulate the total
      response after irradiation, but the impact on the carciongenesis is unknown.

PMID- 15732772
TI  - [Expression of glutathione-S-transferase isoenzymes in larynx cancer].
AB  - Carcinoma planoepitheliale of larynx is the most common cancer present in the
      upper part of the respiratory system. The molecular mechanism of this cancer
      generation is unknown and there is no a specific marker for its early diagnosis.
      The properties, physiological function, as well as the results of studies on
      genetic polymorphism indicate that glutathione-S-transferase (GST) may play an
      important role in etiology of this cancer. In the present work the studies on
      expession of GST isoenzymes pi, alfa, mu4, and mu5 in larynx cancer (carcinoma
      planoepitheliale laryngis) were performed. Specimens of larynx cancer and their
      corresponding normal adjacent tissues were obtained from patients by surgery.
      Expression was studied on the level of mRNA using RT-PCR method. The results
      indicated raised expression of GST pi (the major isoform in larynx) and lowered
      expression of GSTs mu4 and alfa in cancer as compared with the control tissue. No
      expression of GST mu5 was observed in tumor and normal larynx tissues. Obtained
      results indicate various mechanism in regulation of GSTs expression in cancerous
      and normal larynx tissues. They also indicate a special role of GST pi in larynx
      carcinogenesis.

PMID- 15732773
TI  - [Adenolymphoma of parotid gland--analysis of 75 cases].
AB  - The authors present a clinical analysis of the group of 75 patients, who was
      treated in Department of Otolaryngology in the years 1986-2000 and who was
      diagnosed as adenolymphoma. The frequency of incidence of Warthin's tumour is
      17,6% of all 426 cases of parotid gland's tumours. In 72 cases (96%) the tumour
      was localized in the superficial part, only in 3 cases (4%)--in the deep part of
      the gland. In one patient we observed recurrence of adenolymphoma. In one case
      adenolymphoma coexisted with carcinoma planoepitheliale of parotid gland.

PMID- 15732774
TI  - Lymphangioma and lymphangiomyomatosis--the same lesion?
AB  - The authors present a very rare case observed in a 32 year old female with a huge
      tumor on the left side of the neck in which extensive changes characteristic for
      cystic lymphangioma in the lower part and for lymphangiomyomatosis in the upper
      part of the tumor were observed intraoperatively. On the basis of the discussed
      case the suggestion is put forward that these two rarely occurring diseases may
      have similar etiological grounds.

PMID- 15732775
TI  - [Treatment of petrosal cholesteatoma with intracranial extention].
AB  - The authors describe various methods of surgical treatment of extensive petrous
      pyramid cholesteatoma. The surgical technics were selected to each individual
      patient. The approach depended on the disease's course, the lesion extention and
      the ear functional state. Total removing of cholesteatoma were possible by the
      lateral petrosectomy or by the middle fossa approach. The authors underline that
      petrous cholesteatoma can develop after previous radical mastoidectomy. The
      origin of this type of cholesteatoma is usually supratubal recess.

PMID- 15732776
TI  - [Laryngeal radionecrosis].
AB  - Laryngeal radionecrosis is now an uncommon, late complication after radiotherapy.
      The authors presented the diagnostic difficulties with differeniation beetween
      radionecrosis and the recurrent cancer, as well as their own experience with the
      treatment. The material consisted of 6 cases with radionecrosis (Chandler grade
      IV) surgically treated during past 15 years. In 3 cases complications occurred in
      a year after radiotherapy, in 2--ten years and in one--45 years later. In all
      cases repeated biopses were negative. Laryngeal radionecrosis is life threatening
      complication, that is why it requires intensive pharmacological and surgical
      treatment. Despite repeated negative biopses, total laryngectomy is the operation
      of choice when the larynx is non-functioning. In chosen cases, due to often
      observed postoperative complications (necrosis of the skin, pharyngeal fistula),
      indication is the use of artery flaps with simultaneous total laryngectomy.

PMID- 15732777
TI  - [Epidemiological analysis of patients cure in frame of emergency in ORL clinic in
      Warsaw, stepiniska 15/21 in 1996].
AB  - Study the epidemiological and clinical features of patients attending the
      emergency in the Clinic during 12 months to think whether the emergency is still
      needed as a one of method of curing. 4892 patients attended the emergency.
      Parameters analyzed were: age, sex, hour and day of arrival, place of living,
      initial signs, hospitalization and surgical services. The most frequent reasons
      for coming to the emergency were: ear disease (32.2%--middle ear otitis), nose
      disease (662 patients), bleeding nose (559 patients). The most frequent reason
      for hospitalization were swallowed foreign body (16.5%), tumor of the larynx and
      pharynx (16%), vestibulary nerve (12.9%). Emergency is an important sector of
      hospital activity, with a mean 55 per day (week-days), 87 per day (week-end and
      out of job days). The majority men disease were facial traumas, women were
      disease of vestibulary nerve, sudden hearing loss. However, 33% of the
      consultation in the emergency apper to be real medical emergencies, others could
      be appropriately provided by a general practitioner.

PMID- 15732778
TI  - [Reconstruction of lower lip resection defect by using Karapandzic technique-
      early treatment results].
AB  - In 1974 Karapandzic described reconstruction technique of the lower lip resection
      defects by using neuro-vascular flap of the upper lip. In this paper authors
      present six cases of this reconstruction, were defect after resection was in the
      range of 50-80% of lower lip. In all cases the result was excellent, comparing to
      other plastic techniques. Based on the authors scale, functional and aesthetic
      result was scored. Authors suggest that this reconstruction can be an alternative
      to other methods using rotation flaps in particular cases of lower lip cancer.

PMID- 15732779
TI  - [Is syndecan-1 an independent prognostic factor in patients with laryngeal
      carcinoma?].
AB  - Syndecan-1 is a member of the syndecan family of cell membrane heparan sulphate
      proteoglicans. The aim of this study was the evaluation of prognostic value of
      syndecan-1 expression in laryngeal cancer. The findings were correlated with the
      clinico-pathological parameters of the tumours, as well as with patient survival
      rate. Paraffin-embedded samples from 99 patients with laryngeal cancer selected
      from the files of the ENT-Dept. of Medical Academy in Lublin were immunostained
      with anti-syndecan-1 monoclonal antibody. The patients' mean age was 57 years and
      the over 5-year survival rate was 53.2%. Syndecan-1 immunoreactivity was observed
      in 99 (100%) of carcinomas. In our study, a statisti- cally significant
      correlation between syndecan-1 expression and patient survival rate was observed
      (chi2 = 9631; p = 0.008) as well as between syndecan-1 expression and various
      clinical stages of disease (chi2 = 6771; p = 0.034). The significant difference
      in the presence of syndecan-1 expression among the patients with various stage of
      histological differentiation of carcinoma (chi2 = 14.9; p = 0.001), and among the
      patients with present and absent metastatic changes in regional lymph nodes (chi2
      = 16.698; p = 0.001) was observed. In a Coxs multivariate analysis syndecan-1 had
      an independent prognostic value (p = 0.014). Our results indicate that syndecan-1
      could be used as a prognostic marker in laryngeal cancer.

PMID- 15732780
TI  - [The role of hemoglobin concentration in the outcome of definitive radiotherapy
      of the oropharyngeal cancer].
AB  - INTRODUCTION: Squamous cell carcinoma of the oropharynx is potentially curative
      by radiotherapy. The impact on the treatment results have factors related to
      neoplasm, to the patient and factors related to the method of radiotherapy. The
      aim of this paper is evaluation of the impact of hemoglobin concentration (Hb) on
      treatment results in these patients. METHODS: 241 patients with squamous cell
      carcinoma of the oropharynx were treated between 1984-1995 in Radiotherapy
      Department II of Centre of Oncology in Warsaw. Most of them had locally and
      regionally advanced disease (T3-T4 in 63% and N2-3 in 41% of the patients). The
      pretreatment level of Hg was determined. All patients underwent definitive
      radiotherapy with the mean total dose 66-70 Gy. RESULTS: The estimated 5-year
      overall survival in this group was 23%. Analysis of clinical factors and factors
      related to the treatment has shown independent impact of the Hb concentration on
      radiotherapy results. In the group of patients with Hb level above 13 g/dL the
      risk of death and risk of locoregional recurrance were two times lower in
      comparison with group where Hb level was equal to or below 13 g/dL (p = 0.0002
      and p = 0.013 respectively). CONCLUSION: In the group of the patients with
      squamous cell carcinoma of the oropharynx, Hb concentration is important
      prognostic factor of the local control probablility and overall survival.

PMID- 15732781
TI  - [Expression of beta-catenin protein in laryngeal squamous-cell carcinoma].
AB  - beta-catenin and APC are key components of Wnt signaling pathway. Moreover beta
      catenin protein is an adhesion molecule, which exists in complex with E-cadherin.
      Although clinical impact of beta-catenin in laryngeal cancer is still unclear.
      Our purpose was to investigate an expression of beta-catenin and its possible
      prognostic value in laryngeal cancer. The group of 41 patients with laryngeal
      cancer, surgically treated with minimum 5 years observation, was multi-variously
      analysed. Paraffin-embedded tissue sections from each case were
      immunohistochemically stained with a monoclonal antibody raised against beta
      catenin antigen. By univariate analysis expression of beta-catenin analysed on
      the front of laryngeal tumour proved to be significantly related to overall and
      disease free survival, which were shorter in cases with cytoplasmatic expression.
      Although there were co correlation with overall and disease free survival in
      assessment of beta-catenin examined in the middle of tumours. Expression of beta
      catenin in the primary tumours was not associated with its size, nodal status,
      local and nodal recurrences and histological stage (grading). Analysis of beta
      catenin protein expression enables the assessment of biology of laryngeal cancer
      and it can be a prognostic factor of overall and disease free survival, while
      measures on front tumour in patients with laryngeal cancer.

PMID- 15732782
TI  - [Congenital and acquired cholesteatoma middle ear in children].
AB  - Cholesteatoma of the middle ear in children may cause hypoacusis. Early diagnosis
      and optimal treatment is neccessary for good functional effect. We present 57
      children (58 ears) with cholesteatoma treated in ENT Department of Medical
      University in Gdansk in 1991-2002. The age of patients ranged between 3 and 16
      years, the most common 11-15 years. In 52 (89.6%) cases acquired cholesteatoma
      and in 6 (10.4%) congenital cholesteatoma was diagnosed. Epitympanal
      cholesteatoma was found in 32 children (55.1%) whereas in posterior part of
      tympanic cavity--in 20 children (34.5%). In 6 cases (10.4%) intact tympanic
      membrane was found. Mean air-bone gap in acquired cholesteatoma before treatment
      was 18.7 dB, after treatment 15.7 dB. In congenital cholesteatoma mean air-bone
      gap before treatment was 13.6 dB, after treatment 14 dB. The most frequent
      symptom was hearing loss (98.3%) and purulent otorrhea (85.4%). Positive
      bacteriological culture was obtained in 43.1% of the cases. X-ray revealed sclero
      pneumatic mastoid in 26 (34.5%) cases, sclerotic in 25 (43.1%) and pneumatic
      mastoid in 7 (12.1%) cases. Intracranial complications were found in 2 cases,
      intratemporal in 2 cases and extracranial complication in 1 case. Radical surgery
      was performed in 23 cases (39.7%) and in each case, which required reoperation,
      modified radical mastoidectomy in 20 cases (34.4%), in another 15 children
      (25.9%) tympanoplasty was done. The most frequent failure was purulent otorrhea
      in 21 (36.2%) cases. Reoperation in cholesteatoma recurrence was performed in 17
      children (29.3%). Improvement or the same as preoperatively hearing level was
      obtained in 35 (60.3%) ears, hearing loss was revealed in 23 (39.7%) ears.
      Treatment of temporal bone cholesteatoma in children is difficult due to silent
      beginning, aggressive growth and frequent recurrence. The best treatment results
      in children cholesteatoma are obtained in early clinical stage and with open
      tympanoplasty procedure.

PMID- 15732783
TI  - [The changes in the distinctness and discrimination of phonems of cochlear
      implants children].
AB  - Hearing impaired children do not develop oral speech in the same time with the
      hearing ones. Cochlear implants may change this situation. Implanted deaf
      children may develop oral speech but only after long speech rehabilitation.
      Acquisition of language skills should be assesed correctly in every patient. It
      is important because this therapy is quite expensive. There are many quantitative
      and qualitative methods used all over the world. In some cases score is
      calculated as percentage of correctly repeated words. Sometimes it did not
      reflect true level of language development. 240 people were implanted in Poznan
      in years 1994-2004. Two years ago, evaluation of changes in the distinctness and
      discrimination of phonems of cochlear implants children was begun. We found
      differences between standard speech audiometry and distinctness and
      discrimination of phonems.

PMID- 15732784
TI  - [Rare cases of neurofibroina in the head and neck].
AB  - Four cases of neurofibroma rare localized in parapharyngeal space and throat, in
      external ear and larynx are described. Three of them were isolated tumors and in
      one case--tumors in external ears developed in course of general Recklinghausen
      disease. Two cases of neurofibroma in parapharyngeal space had different
      clinical, CT and microscopic picture. In one case tumor protruded the throat
      obturating its oral part with osseous elements in its microscopic structure which
      caused characteristic CT picture. This one was excised through median
      mandibulotomy with good anatomical and functional result. The second case of
      parapharyngeal neurofibroma adherent to the superior cervical vertebra and only
      slightly dislocated the postero-lateral wall of the throat was excised through
      external cervical approach.

PMID- 15732785
TI  - [The case of a great pharyngeal tonsil hypertrophy in a twenty-one-year-old
      patient infected with HIV virus].
AB  - Seropositive patients quite often demonstrate symptoms in the area of the head
      and neck, among which should be mentioned opportunistic infections, neoplasms-
      Kaposi's sarcoma, as well as progressive generalized lymphadenopathy. These
      patients quite often complain about difficulties in breathing through the nose as
      well as of recrudescent auricular inflammation. The authors present descriptions
      of a great pharyngeal and palatal tonsillar hypertrophy in a twenty-one-year-old
      patient infected with HIV virus.

PMID- 15732786
TI  - [Stickler syndrome--case report].
AB  - Stickler syndrome is an autosomal-dominant inherited disorder of connective
      tissue related to incorrect collagen structure. Characteristic signs include
      ocular, hearing, and joint and bone abnormalities. It is hard to assess morbidity
      of Polish population because of lack of full syndrome's expression. In this paper
      we report 6 years old boy, who presented features, first characterized by
      Stickler in 1965.

PMID- 15732787
TI  - [The giant osteoma of the ethmoid labyrinth in the patient cured in 1991 year].
AB  - A 52-year-old female patient is described who was aperated upon for a giant
      osteoma involving the right side ethmoid labyrinth bulging into the orbit
      shifting the eyeball, passing into right of the frontal and sphenoidal sinuses.
      We obtained complete cure and good cosmetic result.

PMID- 15732788
TI  - [Surgical treatment in a case of extensive esthesioneuroblastoma in 77 years old
      female].
AB  - The author presents a case of woman aged 77 with esthesioneuroblastoma of left
      nasal cavity and nasopharynx. There were metastase to cervical lymph nodes. The
      patient was treated surgically and by radiotherapy. The performance of tumor
      removing with conservative bilateral neck dissection was used as surgical
      treatment. Now it has been two years of observation and no renewal of neoplastic
      process was noticed.

PMID- 15732789
TI  - [A case branchogenic cyst of oro- and hypoharynx].
AB  - In this work was described one case branchiogenic cyst of the oro- et
      hypopharynx. Provisional diagnosis was tumor of the neck, because of similar
      symptoms. In the case of brianchiogenic cysts a full diagnostics should be
      formed. The procedures, which enable us to estimate character and extent of a
      lesion and determine the proper surgical treatment, should include
      ultrasonography or CT.

PMID- 15732790
TI  - [Chondroma of the skull base].
AB  - Summary Chondromas of the skull base are extremely rare cartilaginous tumors.
      Etiology of chondromas remains unknown. The clinical presentation and
      radiological findings are not unique and cannot reliably distinguish from other
      similar lesions in this area. The low frequency of patients with chondromas of
      the skull base makes it impossible to draw definitive treatment conclusions.
      Chondromas are benign tumors and have good clinical outcomes. However, follow-up
      depends on localization of the tumor and neighboring vital structures within a
      small area. The authors present a case of 16-year-old patient with chondroma of
      the skull base, followed by a diagnostic evaluation and surgical management.
      Clinical characteristics of the neoplasm was presented on the basis of
      literature.

PMID- 15732791
TI  - [Severe regional and distant complication of tonsillitis. Case report].
AB  - The authors describe a 66-year-old male patient treated for angina that was
      complicated by para- and retropharyngeal phlegmon, mediastinitis and
      pleuropneumonia. The role of imaging procedures and bacteriological examination
      was found especially important in establishing the diagnosis and introducing the
      right treatment. Efficacy of external (transcutaneus) approach to the para- and
      retropharyngeal space and phlegmon drainage of these spaces preceded with
      tracheotomy and tonsillectomy was underlined. Surgical treatment was supplemented
      with multi-component antibiotic therapy and gammaglobulin administration.

PMID- 15732792
TI  - [Primary location of non-Hodgin's lymphoma (type MALT) in hypopharynx--case
      report].
AB  - A rare case of MALT lymphoma of the hypopharynx is presented. The study was
      focused on case history, symptoms and management. In the following paper the
      theories and classification of non-Hodgin's lymphoma are presented.

PMID- 15732793
TI  - [Extramedullary plasmacytoma of the head and neck].
AB  - The aim of this review was to present plasma cell neoplasms, their development,
      common features and classification. Extramedullary plasmacytoma (EMP) is a most
      often plasma cell neoplasm in the head and neck. 80-90% EMP cases concern to head
      and neck: 40% nasal cavity and paranasal sinuses, about 20% nasopharynx, 18%
      oropharynx. Tumour symptoms are similar like in other neoplasm. It is very
      important to remember about plasma cell neoplasm during differential diagnosis
      because of relatively common occurrence. Extramedullary plasmacytoma is
      radiosensitive neoplasm with good prognosis therefore radiation therapy is the
      method of choice.

PMID- 15732794
TI  - [The case of Wegener's disease of the nose, paranasal sinusses and ears].
AB  - The Wegener's granulomatosis is an autoimmunologic disease with still unknown
      etiopathogenesis. A rare case of Wegener's disease in 53-year-old female was
      described, located in her nose, paranasal sinuses and ears. We have also
      presented the diagnostic difficulties with this rare disease.

PMID- 15732795
TI  - [Cervico-facial actinomycosis--case reports].
AB  - In the article the authors made the review of actinomycosis bibliography. They
      also presented characteristic features infections enter ways, course of the
      disease, diagnostic tests and treatment methods. Two cases of face and neck
      actinomycosis were presented. All of them treated in Katowice-Ochojec Hospital
      ENT ward in last five years. Abnormal clinic symptoms made difficulty to put the
      diagnosis. Satisfactory results were achieved after set up final diagnosis and
      proper treatment.

PMID- 15732796
TI  - [The review of anatomical and clinical terminology concerning vocal folds].
AB  - The review of the anatomical and clinical literature of the vocal folds was
      presented. The attention was paid on the lack of homogenous terminology in this
      subject. Different authors use different terms concerning the vocal folds: vocal
      cords, vocal lips and vocal folds. The necessity of developing common, current
      nomenclature of the vocal folds, also due to clinical reasons was emphasized.

PMID- 15732797
TI  - [Application of computer-assisted surgery (CAS) in otolaryngology--head and neck
      surgery].
AB  - There were computer-assisted surgery (CAS) and telemanipulation technics
      presented. They can be used in some surgical procedures. Using available
      literature authors described CAS application in endoscopic paranasal sinus and
      skull base surgery. There were drawbacks and advantages of this methods
      discussed. Moreover there were trends in development of newest technics,
      including robot-aidded surgery (RAS) described.

PMID- 15732798
TI  - [The Polish physicians against adrenaline in otorhinolaryngology in the beginning
      of XX century].
AB  - The exploration of adrenaline in 1901 is depicted first of all. The beginning of
      employment of adrenalin in the diseases of ear, nose, throat and larynx at the
      reports by Andrzej Heiman and Marek Koenigstein is thoroughly described.
      Adrenalin was a unappreciated drug at that time.

PMID- 15732799
TI  - [Cytokines locally produced by lymphocytes removed from the Waldeyers ring
      hypertrophic adenoid tissue].

PMID- 15732800
TI  - [The role of HPV infection in oral cavity, throat and larynx diseases].

PMID- 15732801
TI  - [Report from the 7th European Symposium on Pediatric Cochlear Implantation,
      Geneve, Sept. 2-5, 2004].

PMID- 15732802
TI  - [Diverticulitis (acute)/diverticulosis of the colon].

PMID- 15732803
TI  - [Antithrombotic therapy in patients with first-ever stroke and known non
      rheumatic atrial fibrillation].
AB  - Patients with non-rheumatic atrial fibrillation (AF) have an increased risk for
      ischemic stroke. The presence of risk factors such as a history of ischemic
      stroke, transient ischemic attack, diabetes mellitus, arterial hypertension or
      advanced age allows the classification of patients with AF in three groups with
      high, moderate, and low stroke risk. High-risk patients should receive oral
      anticoagulants, low-risk patients aspirin, and moderate-risk patients one of both
      antithrombotic agents. However, primary stroke prevention studies suggest that
      many high-risk patients are not anticoagulated, whereas low risk patients receive
      anticoagulants instead of aspirin. Our retrospective analysis of prospectively
      collected data examined the antithrombotic therapy of patients with first-ever
      stroke and known non-valvular AF and compared the results with the
      recommendations of the Atrial Fibrillation Investigators (AFI) and the Stroke
      Prevention in Atrial Fibrillation (SPAF) study. Contraindications against
      anticoagulation were taken into consideration. High-risk patients received in 36%
      an appropriate antithrombotic therapy according to the AFI-guidelines, and in 28%
      according to the SPAF-guidelines. About one quarter of low-risk patients were
      anticoagulated unnecessarily. Our study confirms that many patients with AF and
      high stroke risk do not get the appropriate antithrombotic therapy, while some
      patients with low-risk are anticoagulated without cause.

PMID- 15732804
TI  - [Diagnostic yield of the implantable loop recorder to detect the mechanism of
      syncope--a single center long term experience of a tertiary care center].
AB  - AIM: The aim of this study was to investigate the usefulness in providing
      diagnostic information about syncope by implantation of a loop recorder (ILR).
      METHODS AND RESULTS: The study population consisted of 48 consecutive patients
      (23 male, 25 female, mean age 42 +/- 17) with unexplained syncope who presented
      between 1998 and 2002 and underwent extensive cardiological screening and were
      followed with an implantable loop recorder (Reveal or Reveal Plus). The mean
      follow-up duration was 9 +/- 6 months. During this follow-up in 17 (35%) patients
      syncope recurred. Arrhythmia correlating with syncope was documented in 15 (88%)
      of these patients, in 2 (12%) patients an arrhythmia could be excluded. Of these
      15 patients with arrhythmogenic cause of syncope 5 (33%) patients revealed higher
      degree AV-Block, 7 (47%) patients sinus bradycardia or sinus pauses, 4 (27%) due
      to sick sinus syndrome and 3 (20%) due to neurally mediated syncope, 3 (20%)
      patients had atrial tachycardias or atrial fibrillation with rapid AV-conduction.
      As a result of ILR findings 12 pacemakers were implanted and 2 radiofrequency
      ablations were performed. CONCLUSION: The ILR is a valuable and effective tool to
      establish an arrhythmic cause for unexplained syncope. In these cases they have
      an impact on subsequent clinical decision making. ILR can also be useful in
      ruling out arrhythmias as cause of syncope and presyncope.

PMID- 15732805
TI  - [Following tooth loss: fixed partial denture or implant?].

PMID- 15732806
TI  - [Echinococcosis -- a differential diagnosis of calf swelling].

PMID- 15732807
TI  - [Unclear increased ESR].

PMID- 15732808
TI  - [Velvet bean in Parkinson's disease].

PMID- 15732809
TI  - Health care's financial forecast--2005 and beyond.
AB  - Good, bad and ugly may be the best way to describe the financial forecast for
      health care over the next few years. Take a look at some of the factors affecting
      the forecast.

PMID- 15732810
TI  - Engaging physicians in cost savings initiatives. Eliminating medication cost bias
      in the selection of inpatient medications.
AB  - Higher cost medications pose a serious question for physician executives. Learn
      how common administrative databases can provide clinical resource utilization and
      identify success factors and barriers to devising cost-effective medical
      management strategies.

PMID- 15732811
TI  - Why develop a debt policy?

PMID- 15732812
TI  - The people's business: management careers in the public sector.

PMID- 15732813
TI  - Anthrax attacks, hurricanes and flu shot shortage test Agwunobi's skills.

PMID- 15732814
TI  - Lack control: the physician executive's fear.

PMID- 15732815
TI  - Clinical research organizations offer wide range of management opportunities for
      physician executives.

PMID- 15732816
TI  - My first year as chief of staff.

PMID- 15732817
TI  - The traitor complex. MD/MBA students struggle with medicine vs. management
      dilemma.

PMID- 15732818
TI  - What is an evidence-based, value-based health care system? (Part 1).

PMID- 15732819
TI  - Retooling today's practices to accommodate part-time physicians.

PMID- 15732820
TI  - Mapping the future of health care.

PMID- 15732821
TI  - The changing face of gender issues in the 21st century workplace.

PMID- 15732822
TI  - Decision making in uncertainty (Part 1).

PMID- 15732823
TI  - Why did it take so long to make the diagnosis?

PMID- 15732824
TI  - Incidence and clinical background of posttonsillectomy bleeding related blood
      transfusion over 12 years.
AB  - Economies in National Health Systems forces ENT surgeons to review their
      indications for outpatient tonsillectomy. Therefore, it is important to
      preoperatively identify special risk groups who frequently have extensive
      posttonsillectomy bleeding with the need of a blood transfusion. Aim of this
      study was to estimate the incidence for posttonsillectomy bleeding related blood
      transfusion, to identify risk factors associated with the need for blood
      transfusion and to release guidelines for posttonsillectomy bleeding of high risk
      patients. A retrospective study was done on the medical history of 1720 patients
      who underwent tonsillectomy for chronic tonsillitis between 1982-1993 in the ENT
      Department at the University of Kiel. The average transfusion rate was 0.52%. End
      Stage Renal Disease and hypertension combined with a preoperatively decreased Hb
      and Hct were the risk factors identified leading to a transfusion. These patients
      should not get a tonsillectomy as an outpatient procedure. The Hb, Hct, PT, PTT,
      blood type and crossmatch should be drawn and assessed prior to tonsillectomy. We
      recommend immediate treatment of secondary hemorrhage in those high risk patients
      under general anesthesia to avoid severe complications.

PMID- 15732825
TI  - [Cytotoxic T lymphocytes in peripheral blood and regional lymph nodes in
      laryngeal cancer patients].
AB  - Cytotoxic T cells is an unique lymphocyte subpopulation able to recognize in
      specific manner and kill tumor cells. Therefore they constitute an important
      cells engaged in anti-tumor defense. The aim of the study was to determinate
      cytotoxic T cells frequency in peripheral blood and among lymphocytes isolated
      from regional lymph nodes. The study group consisted of twenty patients diagnosed
      with laryngeal cancer subjected surgical treatement. Cytotoxic T cells were
      estimated using three color flow cytometry based on CD3(+)CD8(+)CD28(-)
      GranzymeB(+) phenotype. Additionally TCR zeta chain expression and spontaneous
      apoptosis considered as a potential markers of immunosupressive effect exert by
      tumor were determined. In patients with laryngeal cancer significant increase of
      CD3(+)CD8(+)CD28(-) lymphocytes in peripheral blood in comparison to healthy
      control was observed. In lymph nodes the content of those cells was much lower,
      less than 10%, however in a group bearing metastases to regional lymph nodes
      higher than in a group without metastases. Cytotoxic T cells were also the main
      population subjected spontaneous apoptosis. The role and specificity of cytotoxic
      T cells in laryngeal cancer patients still remain to be elucidated, especially in
      respect to specificity of recognition tumor cell. Understanding details of this
      process may rise significant progress in an approach to diagnosis and therapy in
      laryngeal cancer patients.

PMID- 15732826
TI  - [Usefulness a buccal flaps for reconstruction tissue defects after operations
      cancers lip and nose].
AB  - The aim of this study was to describe methods in tissue reconstruction
      deficiences after operations due to upper and lower lip and nose cancer with
      using full thickness (musculomucosal cutaneus flap) and incomplete buccal flap
      (musculocutaneus). Flaps were collected bilaterally and sutured in the middle of
      the lips. Their usefulness was confirmed especially in total lip reconstruction.

PMID- 15732827
TI  - [Influence of steroid therapy local injection of steroidal in the region of the
      stylomastoid foramen and physiotherapy on the recovery of stapedial reflex in
      patients with facial nerve paralysis].
AB  - There are much more publications which informates about positive effects of
      advisability propose steroid's cure in patients with facial nerve palsy. The aim
      of the studies was to evaluate the influence of steroidal and physical treatment
      on the recovery of stapedial reflex and of functions of the damaged nerve. The
      studies were performed on 37 patients with palsy of facial nerve. Taking into
      account the stapedial reflex (before the beginning of the treatment) and local
      injection of steroidal in the region of the stylomastoid foramen, the patients
      were divided into two groups: I group--21 persons with lacking stapedial reflex,
      who were not given steroid, II group--16 persons with lacking stapedial reflex
      who received steroid. Evaluation of results of treatment was performed by means
      of the Pietruski, House and Brackmann scales, registration of stapedial reflex
      and accommodation coefficient. The results indicate that local steroid in palsy
      facial nerve is the treatment of choice in cases of intratemporal branches injury
      (lack of stapedial reflex) and shortens of duration of stapedial reflex and the
      nerve function recovery.

PMID- 15732828
TI  - [Estimation the effectiveness of cefuroxime therapy in pediatric otolaryngology].
AB  - The authors present results of retrospective clinical analysis of usefulness the
      cefuroxime therapy of acute ENT diseases in children. The study group consist of
      886 patients, aged 4 m. to 17 year, hospitalized at the Department of Paediatric
      Otolaryngology between 1997-2002. The efficacy of therapy was estimated on the
      ground of 4 degree scale. Particular attention was paid on measuring an average
      time of intravenous and oral administration of drug and on side effects of
      treatment. The results of the study shown that cefuroxime therapy is safe and
      effective. Beneficial therapeutic effect was obtained in 98.9% of patients.

PMID- 15732830
TI  - [The prevalence of allergic rhinitis and conjunctivitis in school children from
      Krakow and Poznan--ISAAC study (International Study of Asthma and Allergies in
      Childhood)].
AB  - BACKGROUND: The aim of study was to assess the prevalence of symptoms and
      diagnosis of allergic rhinitis (AR) and allergic rhinitis and conjunctivitis
      (ARC) in school children in 1994/95 and 2001/02. METHODOLOGY: Standardized ISAAC
      questionnaire was used for assessment population of school children 6-7 yrs of
      age and 13-14 yrs of age in Krakow and Poznan. RESULTS: The prevalence of AR ever
      symptoms increased significantly in group 6-7 yrs of age from 28.5% to 33.6% in
      Krakow and from 13.0% to 31.3% in Poznan. The similar rise was found in group 13
      14 yrs of age in Krakow from 26.1% to 41.1%, in Poznan from 19.0% to 39.6%. In
      both age groups and both centers the number of children with established AR
      diagnosis increased: in group 6-7 yrs of age in Krakow from 15.3% to 21.1%, in
      Poznan from 5.0% to 19.5%; in group 13-14 yrs of age in Krakow from 19.7% to
      29.9%, in Poznan from 12.0% to 32.6%. Analysis of AR and ARC current symptoms (in
      the last year) confirmed significant increasing prevalence in both age groups,
      too. CONCLUSION: The prevalence of AR and ARC diagnosis and symptoms increased
      significantly during last 7 years.

PMID- 15732829
TI  - [Neuroendocrine tumors of the larynx].
AB  - The classification, diagnosis, treatment and prognosis of neuroendocrine tumors
      are presented. Rare case of typical carcinoid of the larynx is described. This
      was the second primary tumor after squamous lung cancer treatment. The diagnosis
      was based on routine histological investigation, and then confirmed by
      immunohistochemical tests with synaptophysin, chromogranin, S-100 protein and
      cytokeratin markers. The clinical presentation of the patient, age, gender,
      localization, macroscopic appearance and slow growth dynamic was in accordance
      with cases described in the literature.

PMID- 15732831
TI  - [Near total laryngectomy with internal vocal shunt by Pearson].
AB  - First experience in near total laryngectomy with internal vocal shunt was shown.
      The applications and surgical technique of this method was described. The
      function of the vocal shunt in terms of swallowing, deglutition and phonation
      using endoscopic and radiological examination was presented. Based on previous
      papers the alternative methods of vocal surgical rehabilitation after
      laryngectomy was compared. We have emphasized advantage of this operation in
      selective cases of the laryngeal carcinoma and/or carcinoma of the piriformis
      sinus as well.

PMID- 15732832
TI  - [Results of treatment tinnitus patients using TRT in ENT Rehabilition Center in
      Poznan].
AB  - The authors describe results of treatment tinnitus patients using TRT method.
      Since 4 years over 2000 patients were diagnosed and part of them were treated on
      basis neurophysiological model. In details the authors inform about method TRT
      and estimated results of audiological examination and treatment.

PMID- 15732833
TI  - [Effect of the middle ear status on the recording of vestibular evoked myogenic
      potential--VEMP].
AB  - The aim of this study was to assess the effect of age on the recording of air-
      and bone-conducted vestibular evoked myogenic potential. Forty six young subjects
      were included in the study, ranging in age from 4 to 18 years. All of them
      underwent otoscopy, pure tone audiometry, tympanometry and air- and bone
      conducted VEMP in response to click. Eighty six ears with normal hearing (pure
      tone average 20 dB) and type A and C1 tympanogram were studied. There were 2
      groups according to age: group I--children aged 4-10 years--52 ears, group II-
      young subjects aged 11-18 years--34 ears. The threshold, the presence of correct
      waveform morphology of the response and the latency were evaluated. Above
      parameters were examined at 95 dB and 100 dB (nHL) air conducted click intensity
      and 60 dB (nHL) bone conducted click intensity. The age has no significant effect
      on the percentage of the recording of VEMP and the level of the response
      threshold with air stimulation, based on the performed studies. However, the age
      has effect on the prolongation of latency p13 and n23 both with air and bone
      stimulation. We paid attention to the lower percentage of the recording of bone
      conducted VEMP in young subjects aged 11-18 years.

PMID- 15732834
TI  - [Analysis of the distortion product otoacoustic emission (DPOAE) and input/output
      function (I/O) in tinnitus patient with normal hearing].
AB  - Distortion Product Otoacoustic Emission (DPOAE) has been used as a tool to
      determine the presence of cochlear pathology. It is well known that the damage of
      Outer Hair Cells (OHCs) results in reduced auditory sensitivity and generation of
      tinnitus. At the same time tinnitus arises in normal hearing persons as well. The
      aim of this study was the assessment of the DPOEA amplitude and the behavior of
      DP I/O function in tinnitus patients with normal hearing threshold. The group of
      48 tinnitus patients (92 ears) with normal hearing threshold and the control
      group of 30 normal hearing patients (40 ears) were investigated for this study.
      All subjects have undergone the measurement of DPOAE and DP I/O functions for
      frequencies: 1000, 2000 and 4000 Hz. In the tinnitus group there were observed
      the decrease in DPOAE amplitude for some frequencies and the steeper slope of I/O
      function. This means that the places with localized damage or dysfunction of OHCs
      on the basilar membrane can be responsible for the origin of tinnitus.

PMID- 15732835
TI  - [Diagnostic difficulties in the laryngeal malignant peripheral nerve sheath tumor
      (MPNST)].
AB  - The malignant tumor deriving from the peripheral nerve sheet, previously
      described as malignant Schwannoma or neurosarcoma is extremely rare as malignancy
      localized in the larynx. The half of cases has been developing on the basis of
      neurofibromatosis in von Recklinghausen disease type I or seldom, type II. The
      high grade of malignancy end tendency to reccurences and distant metastases is
      typical for this tumors. The case of 64 year old man with larynx neurosarcoma was
      presented. The diagnostic difficulties were caused by clinical presentation of
      the smooth tumor covered by unchanged mucosa and typical histological features of
      the tumor. The final histological assessment was complemented by positive
      immunohistochemical reaction (antigens against protein S-100, NSE and PG 9.5).

PMID- 15732836
TI  - [Myoepithelial carcinoma of the parotid gland--a case report].
AB  - The case of parotid gland tumour of the carcinoma myoephitelial histological
      structure in 55 year old patient was described in the paper. The patient had the
      surgical treatment of total parotid gland removal with the function of the facial
      nerve preserved and a complementary radiotherapy. The attention is paid to rarity
      of this type of tumour and difficulties in a proper patomorphological evaluation
      requiring special immunohistochemical tests.

PMID- 15732837
TI  - [Hidradenoma of external ear].
AB  - The authors present a rare case of hidradenoma of the external ear and discussed
      the clinical picture, as well as diagnostic and therapeutic procedures.

PMID- 15732838
TI  - [Sudden sensorineural hearing loss as the first symptom of multiple sclerosis.
      Review of literature and case report].
AB  - Sudden sensorineural hearing loss is rarely the first manifestation of multiple
      sclerosis (MS). In the presented case of a 31-year-old woman, sudden hearing loss
      in the left ear was the first monosymptomatic manifestation of the disease. Based
      on clinical evaluation and MRI, we diagnosed the relapsing-remitting variant of
      MS. The several-month long observation of the patient included noting the
      fluctuations in the patient's hearing capability in correlation with the
      continuously abnormal auditory brainstem responses.

PMID- 15732839
TI  - [The case of carcinoma adenoides cysticum of the tongue, the trachea and the
      thyroid gland].
AB  - We present a case of a 65-year-old female patient who was for the first time
      admitted to the clinic in 1997 due to a tuber of the tongue root. The removed
      tuber turned out to be histopatologically a polymorphic adenoma. The patient was
      re-admitted to the Clinic in 2001 due to a tuber of the tongue and of the oral
      cavity bottom. The tuber was removed entirely through a central incision, and an
      apart hypertrophic change has been found on the posterior pharynx wall and in the
      scar after the tracheostomy carried out during the previous surgery. In all cases
      carcinoma adenoides cysticum has been found, as well as metastasis into the
      thyroid gland and the lungs. The patient was qualified for chemotherapy in the
      Institute of Oncology, which she has been going through periodically every two
      weeks until now. In 2002 the patient was operated on a small tuber located
      hypodermically in the scar after the tracheotomy, which was removed. Carcinoma
      adenoides cysticum was found. In November 2002, during the surgery a tumorous
      infiltration of the thyroid gland was found comprehending trachea and reaching
      the mediastenum. In February 2003 the patient was re-admitted to the Clinic due
      to dyspnoea caused by a significant contraction of the trachea which occurred as
      a result of a focus of carcinoma adenoides cysticum and significantly enlarged
      lymph glands near the trachea. The patient was qualified for stent placement in
      the Institute of Pulmonary Disease and Tuberculosis (Instytut Chorob Pluc i
      Gruzlicy). The presented case describes an exceptionally aggressive and polyfocal
      regrowth and transformation of a polymorphic adenoma into cancer.

PMID- 15732840
TI  - [Rare case of primary isolated orbital sarcoidosis in 53 year old woman].
AB  - Isolated to one organ cases of sarcoidosis are observed extremely rare. We
      described a case of 53 year old woman suffer from isolated to orbit form of
      sarcoidosis. Systemic sarcoidosis (lymphadenopathy, pulmonary infiltrates, skin
      lesions) are excluded. The patient was treated by surgery (excision of orbital
      tumor) with following prolonged steroidotherapy. Total retirement of symptoms was
      obtained. During the 19 months follow-up no recurrence have been observed.

PMID- 15732841
TI  - [Acute laryngeal dyspnea in the patient with botulism cured in 2001 year in ENT
      Department Hospital in Kalisz].
AB  - The authors presented symptoms of botulism, diagnostics and treatment. In this
      case there was a necessity of urgent tracheotomy. The authors had good results
      because of early treatment with serum antibotulism A+B+C and symptomatic
      treatment. Decannulation was only after 45 days because the paralytic symptoms
      declined very slowly.

PMID- 15732842
TI  - [Rhabdomyosarcoma embryonale of the middle ear at 55-year-old women].
AB  - The study presents extremely rare of the middle ear rhabdomyosarcoma embryonale
      at 55-year women. Authors showed untypical clinical process and own suspect of
      neoplasm illness. In difficult cases of the middle ear chronic granulomatosis,
      classical HE histological method maybe not enough and should be extended as an
      immunohistochemical examination.

PMID- 15732843
TI  - [A case of Pott's tumor in a 13-year-old boy].
AB  - Pott's puffy tumor is an infrequent entity characterized by subperiosteal abscess
      associated with frontal bone osteomyelitis. It is usually seen as a complication
      of frontal sinusitis. Although cases, in patients of all ages have been reported,
      teenagers are the most frequently affected. Despite modern methods of diagnosis
      and treatment, 9 new cases in children, have been published in the last 7 years.
      This paper describes the case of 13-year-old boy with subperiosteal abscess
      resulting from exacerbation of chronic frontal sinusitis. Complete resolution
      occurred with an intensive antibiotic regime and drainage of frontal sinus and
      subperiosteal abscess.

PMID- 15732844
TI  - [On isolated neck sarcoidosis].
AB  - The authors present actual opinions concerning etiology, pathogenesis and
      diagnostics of sarcoidosis with specific evaluation of the role of T lymphocytes
      and cytokines in formation of sarcoid granulation. Rareness of sarcoidosis in
      that region and difficulties in neck tumours diagnosis is emphasizing. In
      solitary sarcoidosis cases it is necessary to take a sarcoid reaction into
      consideration. It always can go into generalized form. The authors present a case
      of solitary sarcoidosis of the neck.

PMID- 15732845
TI  - [Neurilemmoma of the neck--case report].
AB  - Neurilemmoma is a mild tumor growing from the Schwann's cells of the external
      part of the nerve trunk. Authors, in their works describe a case of a 32-year-old
      man with a neck tumor on its right side. The tumor was identified as the
      neurilemmoma on the grounds of a postoperative histopathological examination.
      Thin-needle biopsy that was made twice during the history of the patient that
      lasted two years did not reveal the character of the tumor.

PMID- 15732846
TI  - [Bilateral internal jugular vein thrombosis following treatment of laryngeal
      carcinoma--a case report].
AB  - The authors present the case of bilateral internal jugular vein thrombosis, which
      was diagnosed in a patient after combined therapy (surgery and radiotherapy)
      because of laryngeal carcinoma. Thrombosis is the frequent complication and the
      second largest death cause from neoplasms. In review of the literature the cases
      of bilateral internal jugular vein thrombosis are uncommon. Jugular vein
      thrombosis has previously been reported in association with deep head and neck
      infections, sepsis, central vein catherization and the neck injuries. Because of
      that the presented case of internal jugular vein thrombosis seems to be
      interesting.

PMID- 15732847
TI  - [Castleman's disease. Case report and review of the literature].
AB  - Authors present a rare case of Castleman's tumor (a hyaline-vascular type)
      located in the neck of 27 year old male. The tumor, sized 5 x 4 cm, was
      surgically removed. The follow up without any sight of recurrence. A review of
      literature is presented, including problems of etiology, pathogenesis, clinical
      presentation, diagnosis, treatment and prognosis of Castleman's disease.

PMID- 15732848
TI  - [A iatrogenic case of foreign body in the frontal sinus].
AB  - The authors show a case of long behinding iatrogenic foreign body in frontal
      sinus, which in spite of over twelve years recurrent pain syndromes hasn't
      diagnosed and treated. Pay attention to great weight of surveyform and stratiform
      radiological investigations in foreign body diagnostic. The patient has been
      operated with retirement syndromes. After operation we have settled supposed
      causes leaving foreign body in frontal sinus.

PMID- 15732849
TI  - [Tumor Abrikossoff of the nasopharynx].
AB  - A case of the nasopharynx tumor is presented. The patient was 67 year old woman.
      In this case Abrikossoff tumor was located within back wall, from the level of
      the right Eustachian tube to the soft palate and upper pol right tonsil.
      Histopathology examination described diagnosis as a Abrikossoff tumor. A rare
      occurrence and localisation of the granular-cell myoblastoma in the nasopharynx
      induced the authors to present this case.

PMID- 15732850
TI  - [Kuttner tumour--review of the literature and report of 3 cases].
AB  - We present 3 cases of Kuttner tumour (or chronic sclerosing sialadenitis of
      submandibular gland) all treated by surgery. In one case we report bilateral
      involvement. The disease was first described by Kuttner more than 100 years ago.
      In the new WHO Classification of tumour-like lesions of the Salivary Glands
      (1992) Kuttner tumour is classified as a distinct clinicopathologic entity. We
      also present a review of the literature about etiology, pathogenesis,
      differential diagnosis and treatment of this disease.

PMID- 15732851
TI  - [Bilateral Warthin's tumor of the parotid gland].
AB  - Three cases of bilateral Warthin's tumor (adenolymphoma) of the parotid gland in
      patients treated in the ENT Department, Medical University of Gdansk were
      presented. They were stated 3.3% of all Whartin's tumors in our institution. In
      two cases the contralateral tumor developed after 2.5 and 15 years and in one
      case arised synchronically. Our three patients were males, 50-65 years old,
      cigarette smokers more than 25 years. All of the patients were treated surgically
      -conservative parotidectomy was performed. We did not observe the complications
      and reccurence of the disease. Opinions on the diagnostic and therapeutic methods
      in that disease reported in Polish and foreign references are discussed.

PMID- 15732852
TI  - [The large tumour of the nasal cavity and paranasal sinuses--a case report].
AB  - The authors described the case of the large tumour of the nasal cavity and
      paranasal sinuses caused total occlusion of the right nasal cavity. The greater
      part of the tumour was outside of the nasal cavity. Computed tomography showed: a
      mass, which filled nasal cavity, maxillary sinus, ethmoid, frontal and
      translocated the septum. The rhinotomy was performed and the large tumour was
      removed. In histopathological test was found: polypus fibrovascularis oedematicus
      in statu inflammationis chronicae.

PMID- 15732853
TI  - [Merkel cell carcinoma of the head and neck].
AB  - Merkel cell carcinoma (MCC) is a skin cancer arising from neurosecretory cells
      which take part in APUD system. In most cases it is locally growing tumor with
      significant tendency to local recurrences after surgery. The authors have
      described four cases MCC localised on the skin of the middle angle of the eye,
      lower eyelid, auricle and cheek, without nodal metastases. All patients have been
      surgery treated, in two cases reconstructive surgery was performed. Radiotherapy
      followed surgery was used for two patients. The authors have reported 5-year
      survival rate in 2 cases, 2-year disease-free rate and 18 month in other cases.

PMID- 15732854
TI  - [From the history of Lodz's otolaryngology].
AB  - Fifty-seven years passed since the creation of the Otolaryngology Chair and
      Clinic is presented. Its organizer and the first head was Professor Henryk
      Lewenfisz-Wojnarowski. In 1946 out of the initiative of the Clinic staff, the
      Lodz's branch of the Polish Otolaryngological Society was founded. In 1947 the
      Clinic took over the building of the Barlicki Hospital and remains there up till
      now. After Professor Lewenfisz-Wojnarowski had moved to Warsaw in 1952, Professor
      Aleksander Radziminski became the head of the Clinic. Since 1972 Professor Jan
      Laciak has been in charge of the Clinic. He has been professionally and
      scientifically involved in its work since 1949. In 1989 Professor Bozydar
      Latkowski became the Chairman of the Clinic. In May 1990 Society for Patients
      after Larynx Surgery was founded and is still active now. In 2000 Professor
      Maciej Gryczynski became the Head of the Chair. Teaching otolaryngology at the
      Medical University of Lodz is based on historical basis of the development of
      this specialization. The academic staff has acquired the experience which enabled
      the development and laid solid foundation for patients diagnosis and treatment,
      as well as graduate and post-graduate education.

PMID- 15732855
TI  - [Has introduction of cocaine helped in development of otorhinolaryngology?].
AB  - The problem of introduction of cocaine in medicine is presented first of all. The
      role of such physicians as Edmund Jelinek, Leopold von Schroetter, Karl Stoerck,
      Philipp Schech, Pierre Fauvel, Emanuel Zaufal, Wilhelm Kirchner, Samuel Meyerson
      and others on introduction of cocaine in otorhinolaryngology is depicted. The
      forms of this drug especially solutions and anxiety in their usage are shown. The
      attempts of use of cocaine into dentistry and into diseases of ear, nose, throat
      and larynx are described in more detail. The another drugs for local anaesthesia
      are depicted finally.

PMID- 15732856
TI  - The effect of basic fibroblast growth factor on delayed-replanted monkey teeth.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF; FGF-2) has been reported to
      facilitate wound healing and periodontal regeneration in experimental alveolar
      bone defects. The purpose of this study was to evaluate histologically the effect
      of topically applied bFGF with or without fibrin glue on delayed-replanted monkey
      teeth prone to replacement resorption. METHODS: Forty-five roots from five
      monkeys were endodontically treated aseptically and then extracted as
      atraumatically as possible. Ten negative control roots were replanted
      immediately, while 12 positive control roots were allowed to bench dry for 1 hour
      prior to replantation, both without further treatment. Roots in the two
      experimental groups were bench dried for 1 hour, rinsed with saline, and then
      replanted into sockets filled with bFGF with (11 roots) or without (12 roots)
      fibrin glue. After 12 weeks, histological sections were prepared and evaluated
      according to morphometric analysis as complete healing or unfavorable healing
      composed of inflammatory resorption and replacement resorption. RESULTS: Kruskal
      Wallis and Mann-Whitney U tests showed teeth in the negative control group to
      have significantly higher complete healing (98.88% +/- 2.30%) and significantly
      lower unfavorable healing (1.12% +/- 2.30%) than the positive control group and
      the experimental groups. bFGF/fibrin glue group showed higher occurrence of
      complete healing (39.06% +/- 41.62%) compared to the bFGF group (25.28% +/-
      28.85%) and the positive control group (16.58% +/- 19.60%), although the
      differences were not significant. Comparing the complete and unfavorable healing,
      there was no significant difference in the bFGF/fibrin glue group (P = 0.47), but
      the differences were significant in the other groups (P < 0.05). CONCLUSION:
      Topical application of bFGF with fibrin glue showed an insignificantly higher
      occurrence of complete healing in delayed-replanted monkey teeth.

PMID- 15732857
TI  - Effect of alendronate on periodontal disease in postmenopausal women: a
      randomized placebo-controlled trial.
AB  - BACKGROUND: We investigated the effect of oral alendronate (ALN) treatment on
      radiological and clinical measurements of periodontal disease in postmenopausal
      women without hormone replacement therapy. METHODS: We evaluated the effect of 6
      months of ALN treatment in 40 postmenopausal women, 55 to 65 years old with
      established periodontal disease, in a controlled, double-masked, prospective
      study. Volunteers were paired by age and randomized to receive ALN (10 mg/day) or
      placebo for the study period. Periodontal mechanical treatment was carried out in
      both groups. At baseline and after treatment, clinical evaluation, hormone blood
      levels, distance from the crestal alveolar bone (CAB) to the cemento-enamel
      junction (CEJ), calcaneus bone mineral density (BMD), hormone levels, serum N
      telopeptide (NTx), and bone-specific alkaline phosphatase (BSAP) were assessed.
      RESULTS: Periodontal disease conditions improved in both groups, but greater
      improvement in probing depth (-0.8 +/- 0.3 mm versus -0.4 +/- 0.4 mm, P = 0.02)
      and gingival bleeding (-0.3% +/- 0.13% versus -0.2% +/- 0.06%, P = 0.006) was
      found in the ALN treated group. Calcaneus BMD increased in the ALN treated group
      (68 +/- 47 mm3 versus -26 +/- 81 mm3, P = 0.0006). CAB-CEJ distance diminished in
      the ALN group (-0.4 +/- 0.40 mm versus 0.60 +/- 0.53 mm, P = 0.00008). Marginal
      reduction in both NTx and BSAP levels was found in the ALN group (-9.4 +/- 6.6
      nmol versus -4.3 +/- 4.7 nmol bone collagen equivalents, P = 0.08, and -7.7 +/-
      8.4 versus -1.5 +/- 5.0 U/l, P = 0.1, respectively). Hormone levels were
      unchanged after treatment. Similar improvement of calcaneus BMD and CAB-CEJ
      distance with ALN treatment was found in obese and non-obese women. CONCLUSION:
      ALN treatment improved periodontal disease and bone turnover in postmenopausal
      women.

PMID- 15732858
TI  - Levels of cytokine receptor activator of nuclear factor kappaB ligand in gingival
      crevicular fluid in untreated chronic periodontitis patients.
AB  - BACKGROUND: Receptor activator of nuclear factor kappaB ligand (RANK-L) is a
      cytokine involved in the regulation of osteoclastogenesis in bone remodeling and
      inflammatory osteolysis. One of the major causes of tooth loss in humans is bone
      destruction. The aim of our study was to determine the presence of RANK-L in
      gingival crevicular fluid (GCF) samples from adult patients with untreated
      chronic periodontitis and in healthy controls. We also identified the RANK-L
      present in lesions undergoing episodic attachment loss from GCF. METHODS: GCF
      samples were collected from two periodontally affected sites (probing depth > or
      = 5 mm, attachment loss > or = 3 mm) in 20 patients (N = 40). After monitoring
      for 4 months, seven patients showed active periodontal disease, and GCF samples
      were collected from one active and one inactive site (N = 14 samples). The
      comparison with healthy controls was carried out by collecting GCF samples from
      12 healthy volunteers (N = 24 samples). GCF was collected using a paper strip,
      and enzyme-linked immunosorbent assay (ELISA) was performed to determine the
      total amount of RANK-L. RESULTS: RANK-L was found in a higher proportion (85%) of
      samples from patients than from controls (46%). The total amount of RANK-L was
      significantly higher in patients (115.53 +/- 78.18 picograms [pg]) than in
      healthy subjects (63.08 +/- 55.08 pg) (P = 0.003). Active sites, presumably
      associated with tissue destruction, had significantly higher levels of RANK-L
      than their inactive counterparts (125.95 pg versus 91.80 pg, P = 0.007).
      CONCLUSION: GCF total amount of RANK-L is significantly increased in periodontal
      disease, supporting its role in the alveolar bone loss developed in this disease.

PMID- 15732859
TI  - The comparative efficacy of stabilized stannous fluoride/sodium hexametaphosphate
      dentifrice and sodium fluoride/triclosan/copolymer dentifrice for the control of
      gingivitis: a 6-month randomized clinical study.
AB  - BACKGROUND: Antimicrobial agents such as stannous fluoride and triclosan have
      been incorporated into dentifrice formulations and have been shown to be
      effective in reducing gingivitis. The objective of this study was to compare the
      anti-gingivitis efficacy of a 0.454% stannous fluoride/sodium hexametaphosphate
      dentifrice to a positive control triclosan/copolymer dentifrice. METHODS: This
      was a 6-month, randomized, double-masked, parallel-group study conducted
      according to the American Dental Association guidelines for evaluating
      chemotherapeutic products for the control of gingivitis. A 0.454% stannous
      fluoride/sodium hexametaphosphate dentifrice was tested against a commercially
      available positive control dentifrice (0.30% triclosan/2.0% Gantrez copolymer).
      Following baseline measurements, subjects received a dental prophylaxis. Subjects
      were then instructed to brush twice daily for 60 seconds using their assigned
      product. Tooth brushing was supervised for 3 days of each week. Clinical
      examinations using a gingival index were performed at baseline and at 3 and 6
      months. RESULTS: A total of 199 subjects were enrolled and 186 completed the 6
      month study. Average baseline gingivitis and bleeding scores were similar for the
      two treatment groups. After 6 months, the experimental group had statistically
      significantly less gingivitis (25.8%) and statistically significantly less
      bleeding (27.4%) on average compared to the control group. Neither adverse oral
      soft tissue effects nor tooth staining were reported. CONCLUSION: Within the
      limits of the study protocol, the results demonstrated superior therapeutic
      benefits for the stabilized 0.454% stannous fluoride/sodium hexametaphosphate
      dentifrice in reducing gingivitis compared to the triclosan/copolymer control in
      this partially supervised study.

PMID- 15732861
TI  - Bucco-lingual crestal bone changes after immediate and delayed implant placement.
AB  - BACKGROUND: Implants placed immediately after tooth extraction offer several
      advantages, but many authors have reported problems in filling the residual gap
      between the implant and the socket walls. Barrier and grafting techniques have
      been tested and yield varying results, so it has been suggested that the timing
      of implant placement may be important for success. The aim of this study was to
      analyze bone healing and coronal bone remodeling around 35 implants, 20 placed
      immediately after tooth removal and 15 placed 6 to 8 weeks after extraction.
      METHODS: All the implants were submerged and placed within the alveoli confines,
      leaving circumferential defects because the implants did not contact the bone at
      their coronal aspects; stabilization was achieved in the bone apically. After
      implant placement the mean distance from buccal bone to lingual bone was 10 mm
      (SD 1.522) for immediate implants and 8.86 mm (SD 2.356) for delayed implants. No
      membrane or filling materials were used. Primary flap closure was accomplished in
      all cases. RESULTS: At second-stage surgery all peri-implant defects were filled,
      and the mean distance from buccal bone to lingual bone was 8.1 mm (SD 1.334) for
      immediate implants and 5.8 mm (SD 1.265) for delayed implants. This pattern of
      coronal bone remodeling, showing a narrowing of the bucco-lingual width, was
      clinically similar for the two groups, although it should be noted that the
      delayed implants exhibited smaller bucco-lingual bone width already at the first
      measurement: it can be speculated that early remodeling may start immediately
      after tooth extraction and continue, non-uniformly, even after delayed implant
      placement. CONCLUSIONS: This study suggests that circumferential defects could
      heal clinically without any guided bone regeneration (GBR) in both experimental
      groups, and that the procedure was virtually free from complications in the
      postoperative period, probably because of the absence of barrier membranes and/or
      grafting materials. Histologically, peri-implant defects of over 1.5 mm heal by
      connective tissue apposition, rather than by direct bone-to-implant contact, but
      clinically this healing may be very successful. No histological analysis was
      carried out in the present study, but even the largest residual gaps were filled
      with hard tissue that could not be probed. Thus, such outcomes can be considered
      clinically successful. The different rate of bone remodeling around immediate or
      delayed implants could have implications for the preferred timing of implant
      placement in sites of high esthetic concern.

PMID- 15732860
TI  - Microbiological changes with the use of locally delivered doxycycline in the
      periodontal treatment of smokers.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of the association
      of locally delivered doxycycline 10% and scaling and root planing in the
      subgingival plaque of smokers. METHODS: Sixteen smokers with chronic
      periodontitis and a minimum of four pockets (> or = 5 mm) on anterior teeth that
      bled on probing were selected. Patients were randomly assigned to one of the
      following groups: scaling and root planing (SRP) or scaling and root planing
      followed by local application of doxycycline (SRP-D). Subgingival plaque samples
      were collected from initially moderate (5 to 6 mm) and deep (> or = 7 mm) pockets
      at baseline and 3 months. Polymerase chain reaction (PCR) analysis was used to
      detect the frequency of Actinobacillus actinomycetemcomitans (Aa), Porphyromonas
      gingivalis (Pg), and Tannerella forsythensis (Tf). RESULTS: No statistically
      significant difference was found in the reduction of Aa in either the SRP-D or
      SRP group (P > 0.05). The reduction in Tf, Pg, and Tf + Pg was statistically
      significant for SRP-D only (P = 0.016, 0.027, and 0.027, respectively). The
      proportion of sites free of Tf at 3 months was 53% for SRP-D and 9% for SRP (P =
      0.02). For Pg, this proportion was 82% and 40%, respectively (P = 0.05).
      CONCLUSION: The use of locally delivered doxycycline may promote the elimination
      of T. forsythensis and P. gingivalis in a greater proportion of sites compared to
      conventional scaling and root planing in smokers.

PMID- 15732862
TI  - Impact of an anti-inflammatory therapy and its withdrawal on the progression of
      experimental periodontitis in rats.
AB  - BACKGROUND: Anti-inflammatory agents have been reported as a bone loss mediator
      in periodontitis. This study aimed to investigate in rats the impact of a
      selective cyclooxygenase-2 inhibitor (meloxicam) on bone loss in ligature-induced
      periodontitis and its post-treatment effect after administration withdrawal.
      METHODS: Seventy-five adult male Wistar rats were included. After anesthesia, a
      mandibular first molar was randomly assigned to receive the cotton ligature in
      the sulcular position, while the contralateral tooth was left unligated. The
      animals were randomly assigned to one of the following five treatment groups (15
      animals each), including daily subcutaneous injections: 1) saline solution for 15
      days; 2) saline solution for 45 days; 3) 3 mg/kg of meloxicam for 15 days; 4) 3
      mg/kg of meloxicam for 45 days; or 5) 3 mg/kg of meloxicam for 15 days followed
      by saline solution for 30 days. The animals were sacrificed and the specimens
      routinely processed. The volume of bone loss was histometrically measured and
      statistical analysis performed. RESULTS: Intergroup comparisons demonstrated that
      the drug may significantly reduce periodontitis-related bone loss (group 3: 5.83
      +/- 2.04); however, this effect is less evident when the drug is administered in
      a short period (group 4: 3.59 +/- 1.57). Moreover, after drug withdrawal, no
      residual effect was observed (6.86 +/- 3.59, 6.09 +/- 2.66, groups 2 and 5,
      respectively) (P > 0.05). CONCLUSIONS: Within the limits of the present study, it
      can be concluded that selective cyclooxygenase-2 inhibitors may reduce bone loss
      associated with experimental periodontitis and that no remaining effect can be
      expected after its withdrawal.

PMID- 15732863
TI  - Augmented transforming growth factor-beta1 in gingival crevicular fluid of
      smokers with chronic periodontitis.
AB  - BACKGROUND: Patients who smoke are at increased risk for chronic periodontitis
      (CP). Also, CP patients who smoke exhibit significantly less reduction of probing
      depths and gains in clinical attachment compared to non-smokers following
      periodontal therapy. Several studies suggest that the effects of smoking on the
      host response may be paramount in regulating the basal systemic inflammatory
      status and therapeutic outcomes in this cohort. Growth factors, specifically
      transforming growth factor beta1 (TGF-beta1), are critical in regulating the
      wound healing response by controlling cell division, differentiation, and
      motility. The hypothesis to be tested was that gingival crevicular fluid (GCF)
      TGF-beta1 production was altered in smokers compared to non-smokers with CP.
      METHODS: GCF was collected from smokers and non-smokers with CP, both at baseline
      and 1 to 2 weeks after initial therapy. GCF volume was determined using an
      electronic device and TGF-beta1 concentration was measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Smokers exhibited a higher mean
      concentration of GCF TGF-beta1 at baseline compared to non-smokers (P = 0.03).
      After initial therapy, smokers exhibited significantly less reduction in mean GCF
      volume compared to non-smokers (P = 0.04). CONCLUSIONS: Augmented constitutive
      production of GCF TGF-beta1 in smokers may explain the clinical appearance of
      fibrotic gingival tissue exhibited by this patient cohort. A diminished reduction
      in GCF volume in smokers following root instrumentation suggests a chronic
      inflammatory status in conjunction with an ineffective host response. These
      findings support the concept that smokers with CP display an altered local
      inflammatory response after initial therapy, perhaps symptomatic of colonization
      by residual periodontal pathogens.

PMID- 15732864
TI  - Association analysis between interleukin-1 family polymorphisms and generalized
      aggressive periodontitis in a Chinese population.
AB  - BACKGROUND: It has been suggested that aggressive periodontitis (AgP) has a
      genetic basis, but this theory has not been confirmed. The intent of this
      investigation was to study whether specific interleukin (IL)-1 genotypes and/or
      alleles could be used to predict susceptibility to generalized AgP (GAgP) in
      Chinese. METHODS: The GAgP group consisted of 122 patients, and the control group
      included 95 healthy subjects. Single nucleotide polymorphisms at IL-1A (+4845)
      and IL-1B (-511, +3954) were analyzed by standard polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) assay. The polymorphism of a
      variable number tandem repeat (VNTR) in intron 2 of IL-1RN was detected by PCR
      amplification and fragment size analysis. RESULTS: There was no significant
      association of IL-1 polymorphisms with GAgP in the unstratified subjects.
      However, when cases were stratified by gender, the frequencies of A2+ genotype
      and allele 2 at IL-1A +4845 were significantly increased in male patients
      compared to male controls (genotype: odds ratio [OR] 5.58, 95% confidence
      interval [CI]: 1.09 to 28.68, P = 0.039; allele: OR 4.97, 95% CI: 1.01 to 24.50,
      P = 0.049; adjusted for age and smoking status). The frequency of IL-1B -511
      A1/A2 heterozygote was significantly increased in male GAgP group compared to
      male controls (adjusted OR 3.16, 95% CI: 1.01 to 9.89, P = 0.048). In females, no
      significant differences were found between patients and controls in corresponding
      analyses at all polymorphic loci. A possible combined effect of IL-1B -511
      polymorphism and smoking on the elevated risk to GAgP was observed. The OR of
      GAgP for combined A2+ genotype and smoking was 12.45 (95% CI: 1.43 to 108.06, P =
      0.022), and for combined allele 2 and smoking was 18.25 (95% CI: 2.32 to 143.86,
      P = 0.006). CONCLUSIONS: The polymorphisms of IL-1A +4845 and IL-1B -511 may play
      an important role in determining GAgP susceptibility in Chinese males.
      Furthermore, a possible combined effect of the polymorphism of IL-1B -511 and
      smoking on GAgP susceptibility was suggested.

PMID- 15732865
TI  - Gingival cell proliferation induced by use of a sonic toothbrush with warmed
      silicone rubber bristles.
AB  - BACKGROUND: Toothbrushing promotes gingival cell proliferation, which may occur
      as the result of the physical stimulation of the gingiva. The present study
      evaluated the effects of temperature and silicone rubber bristles of a sonic
      toothbrush on gingival cell proliferation in dogs. METHODS: During the 5-week
      experimental period, one quadrant in each of eight dogs received a different
      toothbrushing regimen: a manual toothbrush or a sonic toothbrush with 1) nylon,
      2) silicone rubber, or 3) warmed silicone rubber bristles. The proliferative
      activity of gingival cells was evaluated based on expression of proliferating
      cell nuclear antigen (PCNA). RESULTS: Use of the sonic toothbrushes produced a
      higher density of PCNA-positive and total fibroblasts than did use of a manual
      toothbrush. The warm silicone rubber bristles resulted in a higher density of
      PCNA-positive fibroblasts compared with the cooler silicone rubber bristle. The
      number of PCNA-positive basal cells in the junctional epithelium also increased
      following electric toothbrushing with warmed silicone rubber bristles.
      CONCLUSIONS: The sonic toothbrush with silicone rubber bristles induced gingival
      fibroblast proliferation to a greater degree than a manual toothbrush. Warming
      the silicone rubber bristles increased their stimulatory effects on the
      proliferative activity of gingival cells.

PMID- 15732866
TI  - Therapeutic versus prophylactic plus therapeutic administration of omega-3 fatty
      acid on endotoxin-induced periodontitis in rats.
AB  - BACKGROUND: The aim of the present study was 1) to evaluate the possible effects
      of therapeutic usage of omega-3 fatty acid on the gingival tissue levels of
      prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), platelet activating
      factor (PAF), and leukotriene B4 (LTB4) in endotoxin-induced periodontitis in
      rats and 2) to investigate whether prophylactic usage provides any additional
      benefits to therapeutic doses of omega-3 fatty acid. METHODS: Experimental
      periodontitis was induced by repeated injection of Escherichia coli
      lipopolysaccharide (LPS). Thirty-six adult male Sprague-Dawley rats were divided
      into four study groups: 1) saline controls; 2) LPS; 3) therapeutic omega-3 fatty
      acid (TO3); and 4) prophylactic plus therapeutic omega-3 fatty acid (P + TO3)
      groups. In TO3 group, omega-3 fatty acid was given for 15 days following
      induction of experimental periodontitis. In P + TO3 group, omega-3 fatty acid was
      started 15 days before baseline, and then periodontitis was induced at baseline
      and omega-3 fatty acid was continued for 15 days after baseline. On day 15 after
      baseline, all rats were anesthetized and sacrificed. PGE2, PGF2alpha, and LTB4
      levels in gingival tissue samples were analyzed by enzyme immunoassay and PAF
      levels were analyzed by radioimmonoassay. Data were evaluated statistically by
      using parametric tests. RESULTS: LPS injection resulted in significant amount of
      bone loss (P<0.05). Neither therapeutic nor prophylactic plus therapeutic
      administration of omega-3 fatty acid with the doses and duration of therapy used
      in the present study was effective in preventing endotoxin-induced alveolar bone
      loss. TO3 group exhibited significant decreases in the gingival tissue levels of
      PGE2, PGF2alpha, LTB4, and PAF compared to the LPS group (P<0.05). PGE2 and
      PGF2alpha levels in TO3 group were similar to those of the saline group (P>0.05),
      while LTB4 and PAF levels were statistically higher than the saline group
      (P<0.05). Prophylactic plus therapeutic usage of omega-3 fatty acid provided
      similar levels of all these mediators to those of the saline controls (P>0.05).
      CONCLUSIONS: Therapeutic omega-3 fatty acid significantly reduced the gingival
      tissue levels of PGE2, PGF2alpha, LTB4, and PAF in experimental periodontitis.
      Furthermore, prophylactic usage of omega-3 fatty acid provided additional
      beneficial effects to the therapeutic administration by decreasing the gingival
      tissue levels of these mediators to levels of healthy tissue. These findings
      should be verified by longitudinal clinical trials investigating clinical and
      biochemical periodontal parameters to better define the possible role of omega-3
      fatty acids in periodontal treatment.

PMID- 15732867
TI  - Actinobacillus actinomycetemcomitans lipopolysaccharide activates matrix
      metalloproteinase-2 and increases receptor activator of nuclear factor-kappaB
      ligand expression in human periodontal ligament cells.
AB  - BACKGROUND: The lipopolysaccharide (LPS) of A. actinomycetemcomitans is one of
      the major pathogenic factors in periodontal disease. It induces secretion of
      proinflammatory cytokines and is involved in alveolar bone destruction. We
      hypothesized that the LPS of A. actinomycetemcomitans could affect the activation
      of matrix metalloproteinase (MMP)-2 and the expression of receptor activator of
      nuclear factor kappa B ligand (RANKL) and osteoprotegerin in human periodontal
      ligament (HPDL) cells leading to the destruction of periodontium. METHODS: HPDL
      cells were cultured in serum-free medium with or without the LPS of A.
      actinomycetemcomitans for 36 hours. The activation of MMP-2 was analyzed by
      zymography. Changes of the expression of RANKL and osteoprotegerin (OPG) were
      examined by reverse transcription-polymerase chain reaction and supported by
      Western blot analysis. RESULTS: The activation of MMP-2 could be induced by the
      LPS of A. actinomycetemcomitans in HPDL cells and could be inhibited by a serine
      protease inhibitor. This result suggested that the LPS might activate MMP-2
      through a serine protease-dependent pathway. This activation was also blocked by
      NF-kappaB inhibitor, which indicated the involvement of NF-kappaB. The
      upregulation of RANKL but not OPG by the LPS was found in both transcription and
      translation and could be reduced by indomethacin. In addition, serine protease
      inhibitor also inhibited the upregulation of RANKL, suggesting the activity of
      serine protease. CONCLUSIONS: The effect of the LPS of A. actinomycetemcomitans
      on HPDL cells is serum-independent and the induction of the activation of MMP-2
      and the expression of RANKL are serine protease-dependent pathways. The results
      suggest the role of HPDL cells in the pathogenesis of periodontitis.

PMID- 15732868
TI  - Immunohistochemical study of cyclosporin-induced gingival overgrowth in renal
      transplant recipients.
AB  - BACKGROUND: Cyclosporin A (CsA) is an immunosuppressant widely used to treat
      transplant patients and various systemic diseases with immunological components.
      Gingival overgrowth (GO) is a common side effect of CsA administration; however,
      the pathogenesis of drug-induced GO is poorly understood. The aim of this study
      was to evaluate the expression of Ki-67, activation molecules (CD71, CD98),
      leukocytes activation antigens (CD45, CD45RA, CD50, CD11a, CD162, CD227, CD231),
      neurothelin (CD147), and novel endothelial cell antigens (B-F45, SCF87, B-D46, B
      C44, VJ1/6) in gingival tissue in renal transplant recipients treated with CsA.
      METHODS: Tissues from 15 renal transplant patients with significant GO and 10
      systemically healthy control subjects with gingivitis were studied. Frozen
      section biopsies were stained with monoclonal antibodies specific for the above
      mentioned antigens using an indirect immunoperoxidase technique. RESULTS:
      Comparison of the CsA-treated and control groups revealed no significant
      differences with respect to expression of Ki-67; CD50; activation molecules;
      neurothelin; or novel endothelial cell antigens B-D46, B-C44, and VJ1/6. However,
      expression patterns of CD45, CD45RA, CD11a, CD162, CD227, CD231, B-F45, and SCF87
      were significantly different in CsA and control groups. CONCLUSION: Leukocyte
      activation antigens play an important role in CsA-induced gingival overgrowth.

PMID- 15732869
TI  - Distribution of systemic ciprofloxacin and doxycycline to gingiva and gingival
      crevicular fluid.
AB  - BACKGROUND: Systemic fluoroquinolones and tetracyclines reach steady-state levels
      in gingival crevicular fluid (GCF) that are several-fold higher than their levels
      in serum. The mechanism by which this occurs is unclear, but gingival fibroblasts
      are known to accumulate these agents. Uptake by fibroblasts could enhance their
      distribution to gingiva. To test this hypothesis, steady-state levels of these
      agents were assayed in serum, gingival connective tissue (GCT), and GCF. METHODS:
      Healthy subjects who needed resective periodontal surgery participated in the
      study. Approximately 78 hours prior to the surgical appointment, each subject
      began a 3-day regimen of ciprofloxacin or doxycycline. At the surgical
      appointment (scheduled approximately 6 hours after the last dose), samples of
      blood and GCT were collected. GCF samples were collected on paper strips and
      measured with an electronic device. Samples were extracted and analyzed by high
      performance liquid chromatography. RESULTS: Mean ciprofloxacin levels in serum,
      GCT, and GCF were 0.40 microg/ml, 1.38 microg/g, and 1.66 microg/ml, respectively
      (P<0.001, N=9). For doxycycline, these levels were 1.11 microg/ml, 2.03 microg/g,
      and 2.41 microg/ml, respectively (P=0.002, N=8). For both agents, the GCT and GCF
      levels were significantly higher than serum levels (P<0.05), but not
      significantly different from each other. CONCLUSIONS: Our findings suggest that
      fibroblasts could play an important role in the distribution of fluoroquinolones
      and tetracyclines to the gingiva. By accumulating these agents in GCT,
      fibroblasts could contribute to the relatively high levels they attain in GCF.

PMID- 15732870
TI  - Treatment of intrabony defects with bovine-derived xenograft alone and in
      combination with platelet-rich plasma: a randomized clinical trial.
AB  - BACKGROUND: In the treatment of periodontal intrabony defects, the benefits of
      adding platelet-rich plasma (PRP) to a bone replacement grafting material have
      not been tested. The purpose of this study was to compare the clinical outcomes
      obtained by the combination of PRP and a bovine derived xenograft (BDX) to those
      obtained from the use of the bone replacement graft alone. METHODS: Thirteen
      patients were enrolled in a randomized, split mouth, double-masked clinical
      trial. Bilateral defects were matched according to their intrasurgical
      measurements. Qualifying defects had loss of attachment of > or = 6 mm, a
      radiographically detectable defect of > or = 4 mm, at least two remaining osseous
      walls, and not primarily related to a furcation involvement. After the hygienic
      phase, at the baseline examination, probing depth (PD), clinical attachment level
      (CAL), and recession (REC) were measured. During open flap debridement, the
      defects were randomly assigned to receive either BDX mixed with PRP or BDX alone.
      Baseline osseous intrasurgical measurements were obtained. Post-surgical follow
      up and maintenance were performed and PD, CAL, and REC were remeasured at 6
      months. The mean baseline and 6-month PD, CAL, and REC of the deepest buccal and
      lingual measurements related to the defect for each group were computed. The
      change from baseline to 6 months for each parameter measured was calculated. Pre-
      and postoperative comparisons were made between treatment groups at 6 months.
      RESULTS: Randomization of the defects resulted in comparable groups (P > or =
      0.05). At 6 months, paired t test comparisons within groups showed statistically
      significant benefits with both treatment modalities (P < or = 0.05). The mean
      changes (delta) at 6 months for the test and the control groups at the deepest
      sites were: PD reduction: 3.54 and 2.53 mm; CAL gain: 3.15 and 2.31 mm; and REC: 
      0.38 and -0.23 mm, respectively. Paired t test comparisons yielded significant
      differences between treatments for PD and CAL (P < or = 0.05). CONCLUSION: In
      this 6-month clinical trial, the addition of a high concentration of autologous
      platelets to a bovine derived xenograft to treat intrabony defects significantly
      improved their clinical periodontal response.

PMID- 15732871
TI  - A comparative study of root coverage with connective tissue and platelet
      concentrate grafts: 8-month results.
AB  - BACKGROUND: Gingival recession presents destruction of both soft and hard
      tissues. The objectives of this randomized clinical trial were to assess the
      clinical efficacy of platelet concentrate grafts (PCG) in the treatment of Miller
      Class I or II buccal gingival defects and to compare their soft tissue healing
      with those of subepithelial connective tissue grafts (SCTG). METHODS: Seventeen
      arches in 15 patients with bilateral gingival recessions were treated with SCTG
      and PCG covered by coronally advanced flaps. Vertical recession depth (VRD),
      clinical attachment level (CAL), clinical probing depth (PD), and width of
      keratinized tissue (KTW) were measured preoperatively and 8 months postsurgery.
      Surveys on post-surgical discomfort level (PSDL) and manual platelet count were
      also performed. Esthetic outcomes were also evaluated. Paired t test, repeated
      measures analysis of variance (ANOVA), and chi-square and signed-rank tests were
      used to access statistical significance (alpha = 0.05). RESULTS: Mean VRD
      statistically significantly decreased from 2.43 mm presurgery to 0.48 mm with PCG
      (80% root coverage) and from 2.48 mm to 0.17 mm with SCTG (95% root coverage). No
      statistically significant differences between the treatments were found for VRD,
      CAL, and KTW, while mean PD was significantly shallower in the PCG group (1.05
      mm) than that in the SCTG group (1.79 mm). Complete coverage was achieved in 60%
      of the PCG group and in 65.5% of the SCTG group. PSDL was significantly lower in
      the PCG group 1 month post-surgery. Platelet counts demonstrated a five-fold
      increase in PC. Soft tissue in the PCG group demonstrated superior contour and
      texture matching when compared to the SCTG group. CONCLUSIONS: The platelet
      concentrate graft may be an alternative graft material for treating gingival
      recession. Treatment with this graft may result in better esthetic appearance.

PMID- 15732872
TI  - Periodontal repair in dogs: analysis of histometric assessments in the
      supraalveolar periodontal defect model.
AB  - BACKGROUND: Traditionally, the mean value from histometric assessments of several
      histologic sections from the same site has been, used for the histometric
      characterization of the site. The histometric analysis of the supraalveolar
      periodontal defect model uses observations from buccal and lingual sites in three
      step-serial sections representing the central aspect of the mesial and distal
      root for the third and fourth mandibular premolar teeth. The objectives of this
      study were to investigate the correlations and determine whether there are
      significant differences in the measurement values of various histometric
      parameters between the three step-serial sections and to test the hypothesis
      that, in this animal model, histometric assessments using the most central
      section of each root are comparable to the mathematical means of corresponding
      assessments of the site using the three step-serial sections. METHODS:
      Histometric analysis using light microscopy, an attached digital camera system,
      and a personal computer-based image analysis system including a custom program
      for the supraalveolar periodontal defect model was performed on histologic
      sections acquired from one jaw quadrant in each of 12 dogs. The animals had
      received a protocol including placement of a coral biomaterial and guided tissue
      regeneration (GTR) membranes, and were evaluated following a 4-week healing
      interval. Twelve parameters were assessed using three central step-serial
      sections from each root. For each parameter, pair-wise comparisons were performed
      using the mixed models analysis of variance, and the correlations between
      measurements were assessed by the intraclass correlation coefficient (ICC).
      RESULTS: For all parameters assessed, there were no significant differences (P >
      0.05) among the three sections. The differences between the central section and
      the means of the three step-serial sections were small and not statistically
      significant. Parameters that could be assessed on most or all specimens, such as
      defect height and area, membrane height, and bone regeneration area, showed high
      correlations among the three step-serial sections (intraclass coefficient [ICC]
      approximately 0.91 to 0.98), and between each of the three sections and the mean
      for the three step-serial sections (ICC > or = 0.95). The most central section
      had somewhat higher correlation with the mean than measurements made on the
      lateral sections. CONCLUSION: The results suggest that using the supraalveolar
      periodontal defect model representative histometric data can be obtained
      evaluating only the central section from each defect site.

PMID- 15732873
TI  - Endothelial dysfunction in patients with chronic periodontitis and its
      improvement after initial periodontal therapy.
AB  - BACKGROUND: Recent epidemiological data suggested that there is a relationship
      between periodontal health and atherosclerotic coronary heart disease. Although
      hypothetical models were proposed, the exact mechanism of this association has
      not been clarified. The aim of this study is to investigate whether there is an
      endothelial dysfunction in patients with chronic periodontitis and, if present,
      whether recovery is possible with therapy. METHODS: The study groups consisted of
      28 patients (mean age: 45.5 +/- 8.6 years) with chronic periodontitis and without
      any atherosclerotic vascular disease, and 26 healthy controls (mean age: 43.7 +/-
      6.8 years). Cardiovascular risk factors were investigated in both groups.
      Brachial artery responses to reactive hyperemia (endothelium-dependent dilatation
      [EDD]) and sublingual nitroglycerin (endothelium-independent dilatation [EID])
      were measured using high-resolution vascular ultrasound in both groups.
      Measurements were taken before and after initial periodontal therapy in the
      periodontal patients. RESULTS: There was no significant difference between the
      groups with regard to cardiovascular risk factors. In the baseline measurements,
      EDD and EID were significantly impaired in patients with chronic periodontitis
      when compared with the controls (8.4% +/- 4.0% versus 19.4% +/- 8.1%, P<0.0001;
      13.3% +/- 6.3% versus 29.5% +/- 10.0%, P<0.0001 for EDD and EID, respectively).
      After non-surgical periodontal therapy, EDD and EID improved significantly (from
      8.4% +/- 4.0% to 17.7% +/- 5.7%, P<0.0001; and from 13.3% +/- 6.3% to 24.9% +/-
      7.3%, P<0.0001 for FMD and EID, respectively). The EDD and EID changes in the
      controls were insignificant. CONCLUSION: This study showed that endothelial
      functions were impaired in patients with chronic periodontitis and that they
      improve following initial periodontal therapy.

PMID- 15732874
TI  - In vitro biocompatibility of a new titanium-29niobium-13tantalum-4.6zirconium
      alloy with osteoblast-like MG63 cells.
AB  - BACKGROUND: Titanium-29niobium-13tantalum-4.6zirconium (TiNb) has recently been
      developed as a new implant material. TiNb is composed of non-toxic elements and
      has a lower modulus of elasticity than the other titanium alloys. However, its
      biocompatibility has not been adequately characterized. The aim of this study was
      to evaluate the biocompatibility of TiNb using an osteoblast-titanium co-culture
      system. METHODS: MG63 cells were cultured on three kinds of titanium disks: TiNb,
      pure titanium (pTi), and titanium-6aluminum-4vanadium (TiAl), prepared with two
      different surfaces, a polished and acid-etched surface and a machined-grooved
      surface. The surface topography and roughness were evaluated by scanning electron
      microscopy (SEM). After 48 hours culture, the number of proliferating cells and
      prostaglandin E2 (PGE2) production in the culture supernatant were determined.
      RESULTS: There was no significant difference in surface roughness among the three
      titanium disks with a polished and acid-etched surface. After 48 hours of
      culture, the number of cells was significantly reduced on pTi and TiAl compared
      to TiNb and the control. PGE2 production was significantly higher on pTi than on
      TiAl, TiNb, and the control. We further examined the effect of surface roughness
      on PGE2 production using machine-grooved titanium disks. While pTi and TiAl
      stimulated the production of PGE2 depending on surface roughness, roughened TiNb
      did not affect PGE2 production. CONCLUSIONS: These results suggest that TiNb may
      exhibit favorable biocompatibility because it has an efficient surface topography
      for cell proliferation, and the level of PGE2 production does not depend on
      surface roughness. We conclude that TiNb may be useful as an implant material.

PMID- 15732875
TI  - Cementodentinal tear: a case report with 7-year follow-up.
AB  - BACKGROUND: Cemental tears are an uncommon form of root fracture that can lead to
      rapid localized attachment loss. Typically, the separation of the fragment occurs
      at the cementodentinal junction. In this report, we present a case of periodontal
      involvement associated with a cemental tear-like fragment that proved to be a
      cementodentinal tear. We also review the literature on the clinical presentation
      of cemental tear associated periodontal lesions. METHODS: A 52-year-old male
      presented with acute pain on the maxillary right second premolar. Clinically,
      probing depth of 7 mm and inflammation were noted on the distal aspect of tooth
      #4. Radiographic examination revealed separation of cervical root structure on
      the distal aspect of the tooth, involving two-thirds of the root length. The root
      fragment was removed, and the localized defect was treated by open flap
      debridement along with scaling and root planing. The patient was then placed on a
      regular periodontal maintenance schedule. RESULTS: A postoperative probing depth
      of 2 mm with 1 mm recession was recorded at 3 months, and maintained for 7 years.
      Histological examination indicated that the detached root fragment contained
      dentin with overlying acellular cementum and associated periodontal ligament
      tissue. The fragment was estimated to represent as much as 20% of the total root
      surface area. CONCLUSION: Moderate to severe periodontal attachment loss
      associated with cemental or cementodentinal tears, even ones constituting a
      significant portion of the root surface, can be successfully treated with
      conventional periodontal surgical procedures and maintained long term with a
      proper maintenance regimen.

PMID- 15732876
TI  - Desquamative gingivitis associated with IgG/IgA pemphigoid presents a challenging
      diagnosis and treatment: a case report.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP) is a heterogeneous group of
      autoimmune blistering disorders characterized by subepithelial separation and the
      deposition of immunoglobulins and complement along the basement membrane zone
      (BMZ). This disease is diagnosed with direct immunofluorescence testing showing a
      linear deposition of immunoglobulins and/or complement along the BMZ and indirect
      immunofluorescence testing showing circulating IgG (and sometimes IgA)
      autoantibodies along the BMZ. In this case report we describe desquamative
      gingivitis secondary to IgG/IgA pemphigoid and the management of this challenging
      variant of MMP. METHODS: Routine histology, direct immunofluorescence testing,
      and indirect immunofluorescence testing were utilized and correlated to the
      clinical findings to diagnose this unusual immunobullous disease. RESULTS: Direct
      and indirect immunofluorescence testing confirmed the clinical diagnosis of
      IgG/IgA pemphigoid as the cause of desquamative gingivitis and the other mucosal
      findings in this patient. A treatment program including dapsone and other drugs
      completely resolved the oral lesions after 14 months of therapy. CONCLUSIONS:
      Desquamative gingivitis associated with IgG/IgA pemphigoid can be challenging to
      diagnose and treat. After 14 months of treatment, a combination therapy
      consisting of dapsone with cimetidine and vitamin E to enhance drug efficacy and
      frequent intramuscular administrations of triamcinolone achieved control of both
      the oral and genital elements of IgG/IgA pemphigoid in this patient.

PMID- 15732877
TI  - Characterization of Streptococcus constellatus strains recovered from a brain
      abscess and periodontal pockets in an immunocompromised patient.
AB  - BACKGROUND: There have been a number of reports of brain abscesses suggesting an
      odontogenic etiology. However, no efforts have been made to compare brain abscess
      isolates with isolates from the oral cavity using highly discriminative methods.
      We report a brain abscess caused by Streptococcus constellatus in an
      immunocompromised patient where oral infection (periodontitis) was suspected to
      be implicated. METHODS: The brain abscess and oral isolates were compared by
      means of one phenotypic and three genetic (restriction fragment length
      polymorphism [RFLP], ribotyping, and random amplified polymorphic DNA [RAPD])
      fingerprinting techniques. RESULTS: The phenotypic method and RFLP showed
      identical profiles between brain and periodontal isolates, while ribotyping and
      RAPD showed very close similarity, with only one band difference in one of the
      three ribotypes and in one of the three polymorphic RAPD. CONCLUSIONS: Gene
      transfer by genetic recombinational events in the periodontal pocket might have
      been responsible for the emergence of a strain variant of S. constellatus that
      had the potential to cause an abscess at a distant site (brain). The importance
      of odontogenic sources as potential foci of infection for brain abscesses is
      discussed.

PMID- 15732878
TI  - Malignant melanoma of the maxillary gingiva: a case report.
AB  - BACKGROUND: Mucosal malignant melanoma of the of the head and neck is a rare
      neoplasm, accounting for about 0.2% of all melanomas. We present the
      clinopathological findings of a case. METHODS: An 83-year-old woman presented
      with a dark reddish pigmented lesion which had appeared 3 years previously.
      RESULTS: Clinical examination revealed a sessile lesion, 1.5 cm in diameter,
      located on the vestibular maxillary gingiva next to the first molar area.
      Microscopic analysis of the neoplasm showed epithelioid cells with prominent
      nucleoli aggregated in solid nests. Cytoplasmic melanin pigmentation was present.
      The neoplastic cells were positive for HMB-45 and S100 protein. The final
      histologic diagnosis was primary malignant melanoma of the gingiva. Physical
      examination and a computerized tomography scan of the neck, liver, and lungs
      ruled out the possibility of occult melanoma lesions elsewhere in the body.
      CONCLUSION: The prognosis for patients with oral malignant melanoma is extremely
      poor. Earlier recognition of this condition simplifies treatment and greatly
      improves the prognosis for these patients.

PMID- 15732879
TI  - Guided tissue regeneration using a bioabsorbable membrane: a 21-case series.
AB  - BACKGROUND: The purpose of this paper is to demonstrate how a bioabsorbable
      membrane in the treatment of intrabony defects, combined with appropriate case
      selection, produces a significant improvement in the clinical assessment of
      affected teeth. This study demonstrates success in 21 successive cases. METHODS:
      Consecutive patients presenting advanced intrabony defects (8 to 15 mm) meeting
      the predetermined criteria were treated by guided tissue regeneration (GTR) with
      flap debridement and placement of a bioabsorbable copolymer membrane. To evaluate
      treatment predictability in a variety of patients, only one defect per patient
      was included in the study. Twenty-one patients completed the study, which
      included baseline measurement and subsequent surgical reentry of the treated site
      9 to 18 months postoperatively. Selection of lesions was made following
      debridement of the defect; i.e., a membrane was placed only after determining
      that a lesion was a proper candidate for this procedure. Measurements from the
      cemento-enamel junction (CEJ) to the deepest apical aspect of the defects were
      made and documented with photographs. At the time of reentry, defect depths were
      again measured from the CEJ to the deepest apical point along with measurements
      of the residual 3-walled component of the defect, and photographs were taken. The
      re-entry procedure involved an apically positioned and occasionally minor
      osteoplasty to reduce residual probing depth, when present. Radiographs were
      taken at baseline and reentry. RESULTS: The initial mean defect depth, as
      measured from the CEJ to the base of the lesion, was 10.2 mm. The mean defect
      depth at the time of reentry was 5 mm. The mean gain in vertical bone fill was
      5.2 mm. Perhaps more significantly, in 20 of 21 cases, there was vertical fill to
      within 1 mm of the 3-walled component of the residual defect. CONCLUSION: When
      appropriate case selection and management are applied, the use of bioabsorbable
      membranes does provide for consistent and predictable bone fill, producing
      clinically relevant reduction in vertical defect depth.

PMID- 15732880
TI  - Laterally moved, coronally advanced flap: a modified surgical approach for
      isolated recession-type defects.
AB  - BACKGROUND: Various modifications of the laterally sliding flap have been
      proposed to reduce the risk of gingival recession at the donor tooth site, but
      the reported root coverage predictability was quite low. The goal of the present
      study was to evaluate the effectiveness with respect to root coverage of a
      modified surgical approach of the laterally moved flap procedure for the
      treatment of an isolated type of recession defect. METHODS: One hundred and
      twenty (120) isolated gingival recessions (Miller Class I or II) with specific
      features of the keratinized tissue lateral to the defects were treated with a new
      approach to the laterally moved flap. The main surgical modifications consisted
      of the coronal advancement of the laterally moved flap and the different
      thickness during flap elevation. Clinical evaluation was made 1 year after the
      surgery. RESULTS: At the 1-year examination, 97% of the root surface was covered
      with soft tissue and 96 defects (80%) showed complete root coverage. A
      statistical and clinically significant increase of keratinized tissue was
      observed. These favorable results were accomplished with no change in the
      position of gingival margin or in the height of gingival tissue at the donor
      tooth/site. CONCLUSIONS: The laterally moved, coronally advanced surgical
      technique was very effective in treating isolated gingival recessions. It
      combined the esthetic and root coverage advantages of the coronally advanced flap
      with the increase in gingival thickness and keratinized tissue associated with
      the laterally moved flap. The ideal gingival conditions must be present lateral
      to an isolated recession defect in order to render the proposed surgical
      technique an highly effective and predictable root coverage surgical procedure.

PMID- 15732881
TI  - Re: Effect of estrogen and calcitonin therapies on bone density in a lateral area
      adjacent to implants placed in the tibiae of ovariectomized rats. Duarte PM,
      Cesar-Neto JB, Sallum AW, Sallum EA, Nociti FH Jr (2003;74:1618-1624). Re: Guest
      editorial. Consideration of systemic hormone status when treating patients with
      osteopenia. Boyan BD, Schwartz Z (2003;74:1692-1693).

PMID- 15732882
TI  - Profiles in leadership.

PMID- 15732883
TI  - Essentials of hospice: what every Oklahoma physician needs to know, Part I.
AB  - Every physician, regardless of specialty, must advocate and facilitate patient
      access to comprehensive palliative and hospice care as their patients enter the
      last phase of life due to advanced disease or a terminal condition. Accordingly,
      physicians must become familiar with both the general and the disease-specific
      eligibility guidelines for hospice, the different levels of hospice care,
      physician re-imbursement for hospice patient care, and become knowledgeable in
      advance healthcare planning. The latter includes an understanding of Oklahoma's
      DNR law and the Advance Directive for Health Care (Living Will) law. Physician
      proficiency in the palliation of pain and non-pain symptoms that occur in
      patients at end-of-life is critical to alleviate patient suffering and to ensure
      the patient's peaceful dying.

PMID- 15732885
TI  - Patient pages. How to reduce stress at Christmas.

PMID- 15732884
TI  - Caffeine and psychiatric symptoms: a review.
AB  - Caffeine is a widely used psychoactive substance that has the potential to
      contribute to many psychiatric symptoms. This review article aims to address the
      specific research studies and case reports that relate caffeine to psychiatric
      symptoms. Caffeine can cause anxiety symptoms in normal individuals, especially
      in vulnerable patients, like those with pre-existing anxiety disorders. Caffeine
      use is also associated with symptoms of depression due to either a self
      medication theory, or a theory that caffeine itself causes changes in mood.
      Psychosis can be induced in normal individuals ingesting caffeine at toxic doses,
      and psychotic symptoms can also be worsened in schizophrenic patients using
      caffeine. Sleep and symptoms of ADHD may be altered by caffeine as well.
      Prevention of caffeine-induced psychiatric symptoms is possible by recognizing,
      educating, and treating patients using a tapering approach.

PMID- 15732886
TI  - Alzheimer's disease: clinical evaluation and disease management--update.

PMID- 15732887
TI  - Specialty hospitals.

PMID- 15732888
TI  - Closing your practice checklist.

PMID- 15732889
TI  - Occupational radiation exposure: population studies.
AB  - Occupational exposure to ionizing radiation in the medical setting differs from
      the acute exposure received by survivors of atomic bomb blasts. Yet, atomic bomb
      survivors' disease and mortality outcomes have been the standard data source on
      the effects of ionizing radiation on humans. Therefore, the prevailing estimated
      risks of ionizing radiation may not apply to radiologic technologists and other
      medical radiation workers. Carefully designed epidemiological trials provide
      evidence that helps determine the strength of association between exposure and
      onset of disease in selected populations. This article reviews radiation effects,
      explains some basic design concepts of epidemiologic trials and surveys the
      epidemiology literature related to radiation exposure to humans, with special
      attention to radiology staff.

PMID- 15732890
TI  - The stability of dry and wet laser imaging systems.
AB  - This study investigated the comparative stabilities of wet and dry laser imaging
      systems using 4 different imagers: 2 wet and 2 dry systems. Fifteen step wedge
      films, generated by built-in software from each imager, were collected over a
      period of 25 days. The stability of each system was assessed by computing the
      average and standard deviation of the percentage coefficients of variation for
      the optical densities of the steps. Small, but statistically significant,
      differences between the mean coefficient of variation values were found, with no
      significant trend toward either system. Wet imaging systems recorded lower speed
      index values than dry systems, but there was no definite trend toward either type
      for contrast index. Both imaging systems are equally stable in their performance;
      however, regular quality control checks are essential to monitor abnormal
      behavior.

PMID- 15732891
TI  - Panoramic radiography.

PMID- 15732892
TI  - Radiologic sciences. Faculty needs assessment.
AB  - A total of 326 programs are represented in the data collected. Based on the
      average number of full- and part-time faculty members reported per program, this
      survey represents more than 1500 faculty positions. Based on the forecast of
      retirement and career change for all faculty members, there will be a turnover of
      700 to 800 positions over the next 5 to 10 years. Part-time/adjunct faculty
      vacancies are expected to create the greatest number of opportunities for
      technologists to make the transition to education, with approximately one third
      of current part-time/adjunct educators planning on leaving radiologic sciences
      education within 5 years. To encourage retention of part-time/adjunct educators,
      annual evaluations should be modified to recognize the important educational role
      these instructors play. There is a need to create enthusiasm and interest in
      education as a career pathway for radiologic technologists. Resources are needed
      that help radiologic technologists make the transition to teaching. Finally, the
      retention of educators must be emphasized. Program applicant trends indicate
      radiologic technology students are older, have prior postsecondary education
      experience or are making a career change. This data emphasizes the need for
      educators, both full time and part time, to understand the characteristics and
      needs of the adult learner. Adult learners bring a wealth of education,
      experience and life skills that create both opportunities and challenges in the
      classroom and clinical setting. All categories of respondents indicated that
      their current salaries were greater than those of program graduates in their
      firstjob. Of interest is that 1 in 5 (20%) of part-time/adjunct educators
      indicated the opposite--that program graduates earn more in their firstjob than
      educators earn. When asked about salaries if working full time in clinical
      practice, the majority of all groups indicated their salary would be about the
      same or would decrease. Only 20% of program directors, 21% of full-time educators
      and 26% of part-time/adjunct educators indicated their salary would be higher in
      clinical practice. Part-time/adjunct educators reported working the most in
      clinical practice within the past week to month. Program directors exhibited the
      greatest separation from clinical practice, with more than half indicating a gap
      of 2 years or more from practicing in the clinical environment. While academic
      achievement is common among the educator populations sampled, a very low
      percentage of these educators are seeking an advanced academic degree. Less than
      a third of those surveyed indicated that they were pursuing an advanced degree.
      Becoming involved in research is not a requirement for many current educators,
      although survey participants expressed an interest in information about how to
      conduct a research project. A primary motivator for conducting the faculty
      development needs assessment was to use the data in strategic planning to set
      priorities for the resources available to the ASRT Education Department. The data
      will help maximize ASRT support for present and future educators. Services
      created by the ASRT Education Department will deepen the relationship with this
      key segment of the professional community.

PMID- 15732893
TI  - Medical imaging and CNS infections.
AB  - West Nile virus, Creutzfeldt-Jakob disease and new-variant CJD are emergent
      infectious diseases that affect the brain. Although incidence of these infections
      is low compared with other CNS diseases such as viral or bacterial meningitis,
      the reasons for their emergence are complex. Scientists believe that unique
      combinations of genetic, environmental and social factors have caused these rare
      pathogens to become more common within human populations. Because the causes of
      brain infections are difficult to diagnose and treat, medical imaging is an
      important screening, diagnostic and monitoring tool. By supplying pathogen
      specific visual clues, medical imaging studies provide the evidence that allow
      clinicians to begin life-saving supportive care and treatment.

PMID- 15732894
TI  - Effective communication affects student achievement and retention.

PMID- 15732896
TI  - Medicare aiming to reduce payment errors.

PMID- 15732895
TI  - Rickets.

PMID- 15732897
TI  - TMJ imaging.

PMID- 15732898
TI  - Thin-layer chromatography and mass spectrometry coupled using desorption
      electrospray ionization.
AB  - Desorption electrospray ionization (DESI) was demonstrated as a means to couple
      thin-layer chromatography (TLC) with mass spectrometry. The experimental setup
      and its optimization are described. Development lanes were scanned by moving the
      TLC plate under computer control while directing the stationary DESI emitter
      charged droplet plume at the TLC plate surface. Mass spectral data were recorded
      in either selected reaction monitoring mode or in full scan ion trap mode using a
      hybrid triple quadrupole linear ion trap mass spectrometer. Fundamentals and
      practical applications of the technique were demonstrated in positive ion mode
      using selected reaction monitoring detection of rhodamine dyes separated on
      hydrophobic reversed-phase C8 plates and reversed-phase C2 plates, in negative
      ion full scan mode using a selection of FD&C dyes separated on a wettable
      reversed-phase C18 plate, and in positive ion full scan mode using a mixture of
      aspirin, acetaminophen, and caffeine from an over-the-counter pain medication
      separated on a normal-phase silica gel plate.

PMID- 15732899
TI  - Carrier medium exchange through ultrasonic particle switching in microfluidic
      channels.
AB  - This paper describes a method, utilizing acoustic force manipulation of suspended
      particles, in which particles in a laminar flow microchannel are continuously
      translated from one medium to another with virtually no mixing of the two media.
      During the study, 5-microm polyamide spheres suspended in distilled water, spiked
      (contaminated) with Evans blue, were switched over to clean distilled water. More
      than 95% of the polyamide spheres could be collected in the clean medium while
      removing up to 95% of the contaminant. Preliminary experiments to use this method
      to wash blood were performed. Red blood cells were switched from blood, spiked
      with Evans blue, to clean blood plasma. At least 95% of the red blood cells
      (bovine blood) could be collected in clean blood plasma while up to 98% of the
      contaminant was removed. The obtained results indicate that the presented method
      can be used as a generic method for particle washing and, more specifically, be
      applied for both intraoperative and postoperative blood washing.

PMID- 15732900
TI  - Stoichiometric selection of tight-binding inhibitors by wild-type and mutant
      forms of malarial (Plasmodium falciparum) dihydrofolate reductase.
AB  - A simple method for screening combinatorial and other libraries of inhibitors of
      malarial (Plasmodium falciparum) dihydrofolate reductase (PfDHFR) has been
      developed, based on the affinities of the inhibitors with the enzyme. In the
      presence of limiting amounts of the enzyme, a number of inhibitors in the library
      were bound to extents reflecting the relative binding affinities. Following
      ultrafiltration and guanidine hydrochloride treatment to release bound
      inhibitors, the amounts of free and bound inhibitors could be determined by high
      performance liquid chromatography and liquid chromatography-mass spectrometry.
      The differences in the patterns reflected the binding of high-affinity components
      compared with the other members in the library. A good correlation was found
      between the inhibition constants (Ki values) and the extent of binding of
      inhibitors to wild-type, double (C59R+S108N) and quadruple mutant
      (N51I+C59R+S108N+I164L) of PfDHFR, as well as human DHFR. In addition to
      identifying lead components of the libraries with high affinities (low Ki values)
      and stabilities (low k(off) rates), this simple method also provides an
      alternative way for quickly and accurately calculating enzyme binding affinities
      of inhibitors in combinatorial chemical libraries.

PMID- 15732901
TI  - Quantitative Raman reaction monitoring using the solvent as internal standard.
AB  - Despite its potential, the use of Raman spectroscopy for real-time quantitative
      reaction monitoring is still rather limited. The problems of fluorescence, laser
      instability, low intensities, and the inner filter effect often outscore the
      advantages as narrow bands, the use of glass fibers, and low scattering of water
      and glass. In this paper, we present real-time quantitative monitoring of the
      catalyzed Heck reaction by using the solvent as internal standard. In this way,
      all multiplicative distortions, e.g., laser intensity variations or absorbance of
      the laser light, can be corrected for. We also show that a limited amount of
      fluorescence does not hamper the analysis. Finally, we present a new method to
      correct for the inner filter effect, i.e., the absorbance of Raman scattered
      light by the reaction medium. Simultaneous absorption measurements of the
      reaction mixture enable accurate correction of Raman signals for the inner filter
      effect. Thus, for reaction monitoring applications, a Raman spectrometer should
      be equipped with an absorbance measurement device.

PMID- 15732902
TI  - Electromigration of single molecules of DNA in a crystalline array of 300-nm
      silica colloids.
AB  - The velocities and conformations of single DNA chains were probed as they
      electromigrated at varying electric field strength through a crystalline array of
      silica colloids. An optically transparent film consisting of 300-nm silica
      colloids was formed on glass as a transparent crystalline layer of 7 mum
      thickness with an effective pore size of 45 nm. The behaviors of individual
      lambda-DNA molecules (48,502 base pairs) electromigrating through this material
      were observed to be analogous to the behaviors of long DNA chains in
      electrophoresis gels, including chain extension, hooking of chains around the
      matrix, and hernia formation. The electrophoretic mobility of lambda-DNA in this
      dense, narrow-pore material is surprisingly high: 1.8 cm2/Vs at 10 V/cm, which is
      at least as high as for much wider-pore gels. Imaging of the single molecules
      revealed that higher field strength caused increased chain extension and
      increased mobility, which reached an apparent plateau just above 2.0 cm2/Vs at
      200 V/cm. Pulsed, crossed electric fields of 200 V/cm at 120 degrees to one
      another were applied to the material. The DNA chains were observed by imaging to
      electromigrate in an orderly fashion, and the migration rate was found to be
      length-dependent. The results indicate that these thin, robust, self-assembling
      inorganic materials are interesting as possible alternatives to polymeric gels
      for higher speed electrophoresis.

PMID- 15732903
TI  - Mesoscopic simulation of adsorption of peptides in a hydrophobic chromatography
      system.
AB  - Mesoscopic simulations using Langevin dipoles on a lattice for the solvent and
      calculated partial charges for the solute have been used to estimate free
      energies of adsorption from data on reversed-phase chromatography on nine
      protected peptides covering a wide range of structures. There is a single
      parameter, the effective solvent dipole moment, that is fit to data for one
      peptide and used to predict properties of the other eight peptides. Good
      agreement of adsorption chemical potentials, including order of chromatographic
      retention times, is found for calculations that are Boltzmann-averaged over a set
      of orientations. In addition, the results suggest that there are preferential
      orientations for each peptide at the model hydrophobic chromatographic surface.
      Estimation methods for adsorption based on molecular descriptors and
      hydrophobicity scales are shown to be unreliable for these systems. With
      refinements and extensions, this simulation method should be applicable to
      solvents containing salt, such as in hydrophobic interaction chromatography, and
      to larger solutes including proteins.

PMID- 15732904
TI  - In situ visualization and characterization of aerosol droplets in an inductively
      coupled plasma.
AB  - Laser-scattering techniques are utilized for the first time to visualize the
      aerosol droplets in an inductively coupled plasma (ICP) torch from the nebulizer
      tip to the site of analytical measurements. The resulting images provide key
      information about the spatial distribution of the aerosol introduced by direct
      injection and conventional sample introduction devices: (1) a direct injection
      high-efficiency nebulizer (DIHEN); (2) a large-bore DIHEN; and (3) a MicroFlow
      PFA nebulizer with a PFA Scott-type spray chamber. Moreover, particle image
      velocimetry is used to study the in situ behavior of the aerosol before
      interaction with the plasma, while the individual surviving droplets are explored
      by particle tracking velocimetry. Directly introduced aerosols are highly
      scattered across the plasma torch as a result of their radial motion, indicating
      less than optimum sample consumption efficiency for the current direct injection
      devices. Further, the velocity distribution of the surviving droplets
      demonstrates the importance of the initial droplet velocities in complete
      desolvation of the aerosol for optimum analytical performance in ICP
      spectrometries. These new observations are critical in the design of the next
      generation direct injection devices for lower sample consumption, higher
      sensitivity, lower noise levels, suppressed matrix effects, and developing smart
      spectrometers.

PMID- 15732905
TI  - Pigment identification by spectroscopic means: evidence consistent with the
      attribution of the painting Young Woman Seated at a Virginal to Vermeer.
AB  - Technical examination of the painting Young Woman Seated at a Virginal by cross
      section and polarized light microscopy, chemical tests, surface microscopy,
      energy-dispersive X-ray analysis, and Raman microscopy has led to the
      identification of the pigments lead tin yellow (type I), lazurite, vermilion,
      calcite, lead white, red and yellow iron oxides, umber, lamp black, and green
      earth on the canvas. These pigments are entirely typical of Vermeer's palette and
      are consistent with a large body of other technical and art historical findings
      on paintings by Vermeer and other Dutch 17th century artists. While not
      authenticating the painting as being by Vermeer, the results provide further
      critical material that is consistent with this attribution. This case study also
      provides an opportunity to outline the role of analytical and forensic sciences
      in the examination and attribution of art objects.

PMID- 15732906
TI  - Global kinase screening. Applications of frontal affinity chromatography coupled
      to mass spectrometry in drug discovery.
AB  - Utilizing frontal affinity chromatography with mass spectrometry detection (FAC
      MS), we have identified novel applications in the discovery of small-molecule
      hits to protein targets that are difficult if not impossible to accomplish using
      traditional assays. We demonstrate for the first time an ability to distinguish
      between competitive ligands for the ATP and substrate sites of protein kinase C
      independently in the same experiment and show that ATP competitive ligands using
      a functionally inactive receptor tyrosine kinase can be identified. This ability
      of FAC-MS to simultaneously monitor binding at the ATP and substrate binding
      sites, as well as measure ligand binding to both active and inactive kinases,
      suggests that FAC-MS can be used as a "global kinase binding assay".

PMID- 15732907
TI  - Novel hydrophobicity ruler approach for determining the octanol/water partition
      coefficients of very hydrophobic compounds via their polymer/solvent solution
      distribution coefficients.
AB  - A novel hydrophobicity ruler approach for determining the octanol/water partition
      coefficients of very hydrophobic compounds is proposed, which is an indirect
      method that measures the polymer/solvent solution distribution coefficients (log
      Kp/s) of reference and unknown compounds. The log Kp/s values of the unknown
      compounds can be calibrated to their log Ko/w values via the correlation of the
      log Kp/s values of the reference compounds with their log Ko/w values. An organic
      solvent was used to increase the solubility of the very hydrophobic compounds in
      the aqueous solution, so that their concentrations and absorption amounts were
      high enough to be measured precisely. The solvent also reduced the hydrophobicity
      scale of the very hydrophobic compounds and controlled the amounts absorbed into
      the polymer phase, so that compounds spanning a very wide range of log Ko/w
      values could be measured in a single measurement and the coexisting compounds
      would not interfere each other. Poly(dimethylsiloxane) (PDMS), aqueous methanol
      solutions, and a series of 21 PCB (polychlorinated biphenyl) compounds were used
      to demonstrate the principle of the hydrophobicity ruler approach. The PCB
      compounds with known experimental log Ko/w values served as reference compounds,
      whereas the PCB compounds without known log Ko/w values were determined. The log
      Ko/w values determined for PCB126, PCB187, PCB197, PCB180, PCB170, and PCB195
      were 6.94, 7.84, 8.33, 8.17, 7.92, and 8.49, respectively. The correlation of the
      log Kp/s values of the reference PCB compounds with their log Ko/w values was
      linear (log Ko/w=2.56 log Kp/s+1.08, R2=0.95). The hydrophobicity ruler approach
      is also a valuable tool for validating the experimental and theoretical log Ko/w
      values and identifying outliers in log Ko/w databases.

PMID- 15732908
TI  - Statistical total correlation spectroscopy: an exploratory approach for latent
      biomarker identification from metabolic 1H NMR data sets.
AB  - We describe here the implementation of the statistical total correlation
      spectroscopy (STOCSY) analysis method for aiding the identification of potential
      biomarker molecules in metabonomic studies based on NMR spectroscopic data.
      STOCSY takes advantage of the multicollinearity of the intensity variables in a
      set of spectra (in this case 1H NMR spectra) to generate a pseudo-two-dimensional
      NMR spectrum that displays the correlation among the intensities of the various
      peaks across the whole sample. This method is not limited to the usual
      connectivities that are deducible from more standard two-dimensional NMR
      spectroscopic methods, such as TOCSY. Moreover, two or more molecules involved in
      the same pathway can also present high intermolecular correlations because of
      biological covariance or can even be anticorrelated. This combination of STOCSY
      with supervised pattern recognition and particularly orthogonal projection on
      latent structure-discriminant analysis (O-PLS-DA) offers a new powerful framework
      for analysis of metabonomic data. In a first step O-PLS-DA extracts the part of
      NMR spectra related to discrimination. This information is then cross-combined
      with the STOCSY results to help identify the molecules responsible for the
      metabolic variation. To illustrate the applicability of the method, it has been
      applied to 1H NMR spectra of urine from a metabonomic study of a model of insulin
      resistance based on the administration of a carbohydrate diet to three different
      mice strains (C57BL/6Oxjr, BALB/cOxjr, and 129S6/SvEvOxjr) in which a series of
      metabolites of biological importance can be conclusively assigned and identified
      by use of the STOCSY approach.

PMID- 15732909
TI  - Volume cytometry: microfluidic sensor for high-throughput screening in real time.
AB  - Regulation of cell volume was one of the earliest evolutionary demands for life
      and remains a universal measure of cell metabolism. Since conventional methods to
      measure cell volume, such as microscopy, are complex and time-consuming, cell
      volume has not been used as the basis for cell-based screening. We have developed
      a microfabricated chip that can measure the volume of small numbers of cells in
      real time with unprecedented resolution. The method is applicable to adherent or
      suspended populations of cells and membrane-bound organelles. Our prototype
      device can detect volume changes in a monolayer of tissue-cultured astrocytes
      responding to anisotonic stimuli of <1mOsm. We determined the sensitivity to
      antibiotics of different E. coli strains in <10 min at 24 degrees C. This time
      can be reduced at higher temperatures enabling on-site clinical testing of
      infectious agents. Using the chip to screen natural products, we found a peptide
      in spider venom that inhibits eukaryotic volume regulation at approximately
      100pM. The prototype chip made in silicon is inexpensive, reusable, and runs on
      low-voltage electrical power. The technology can be readily transferred to large
      arrays in plastic.

PMID- 15732910
TI  - Firefly luciferase enzyme fragment complementation for imaging in cells and
      living animals.
AB  - We identified different fragments of the firefly luciferase gene based on the
      crystal structure of firefly luciferase. These split reporter genes which encode
      for protein fragments, unlike the fragments currently used for studying protein
      protein interactions, can self-complement and provide luciferase enzyme activity
      in different cell lines in culture and in living mice. The comparison of the
      fragment complementation associated recovery of firefly luciferase enzyme
      activity with intact firefly luciferase was estimated for different fragment
      combinations and ranged from 0.01 to 4% of the full firefly luciferase activity.
      Using a cooled optical charge-coupled device camera, the analysis of firefly
      luciferase fragment complementation in transiently transfected subcutaneous 293T
      cell implants in living mice showed significant detectable enzyme activity upon
      injecting d-luciferin, especially from the combinations of fragments identified
      (Nfluc and Cfluc are the N and C fragments of the firefly luciferase gene,
      respectively): Nfluc (1-475)/Cfluc (245-550), Nfluc (1-475)/Cfluc (265-550), and
      Nfluc (1-475)/Cfluc (300-550). The Cfluc (265-550) fragment, upon expression with
      the nuclear localization signal (NLS) peptide of SV40, shows reduced enzyme
      activity when the cells are cotransfected with the Nfluc (1-475) fragment
      expressed without NLS. We also proved in this study that the complementing
      fragments could be efficiently used for screening macromolecule delivery vehicles
      by delivering TAT-Cfluc (265-550) to cells stably expressing Nfluc (1-475) and
      recovering signal. These complementing fragments should be useful for many
      reporter-based assays including intracellular localization of proteins, studying
      cellular macromolecule delivery vehicles, studying cell-cell fusions, and also
      developing intracellular phosphorylation sensors based on fragment
      complementation.

PMID- 15732911
TI  - Isoelectric focusing in a poly(dimethylsiloxane) microfluidic chip.
AB  - This paper reports the application of ampholyte-based isoelectric focusing in
      poly(dimethylsiloxane) (PDMS) using methylcellulose (MC) to reduce electroosmosis
      and peak drift. Although the characteristics of PDMS make it possible to
      fabricate microfluidic chips using soft lithography, unstable electroosmotic flow
      (EOF) and cathodic drift are significant problems when this medium is used. This
      paper demonstrates that EOF is greatly reduced in PDMS by applying a dynamic coat
      of MC to the channel walls and that higher concentrations of MC can be used to
      increase the viscosity of the electrode solutions in order to suppress pH
      gradient drift and reduce "compression"of the pH gradient. To illustrate the
      effect of MC on performance, several fluorescent proteins were focused in
      microchip channels 5 microm deep by 300 microm wide by 2 cm long in 3-10 min
      using broad-range ampholytes at electric field strengths ranging from 25 to 100
      V/cm.

PMID- 15732912
TI  - Arrays and cascades of fluorescent liquid-liquid waveguides: broadband light
      sources for spectroscopy in microchannels.
AB  - This paper describes the fabrication and operation of fluidic broadband light
      sources for use "on-chip" in integrated microanalytical systems. These light
      sources consist of liquid-core, liquid-cladding (L2) microchannel waveguides with
      liquid cores containing fluorescent dyes, excited by incident light from an
      external halogen bulb. Simultaneous use of multiple fluorophores in a common
      solution, in a single L2 light source, is not possible, because energy transfer
      from fluorophores emitting at shorter wavelength to fluorophores emitting at
      longer wavelength is essentially complete. Two approaches circumvent this problem
      of energy transfer; both use spatial separation of the fluorophores in different
      streams. The first setup uses a cascade (series) of single-core, single-dye light
      sources of increasing absorption energy to generate a combined broadband output.
      The second approach uses a parallel array of single-core, single-dye light
      sources. The spectral content of the light output for both cascade and array
      light sources can be controlled through choice of flow rates and dyes. Output
      intensity from these light sources is comparable to standard fiber-optic
      spectrophotometer light sources. The paper also discusses the efficiency of
      energy transfer between parallel liquid cores as a function of the fluid medium
      (index of refraction, path length, and rate of flow).

PMID- 15732913
TI  - Instrumentation and method for ultrahigh resolution field desorption ionization
      fourier transform ion cyclotron resonance mass spectrometry of nonpolar species.
AB  - We describe the construction and application of a 9.4-T FT-ICR mass spectrometer
      interfaced to a commercial field desorption ion source for high-resolution, high
      mass accuracy measurements of nonpolar species. The FT-ICR MS instrument includes
      a liquid injection field desorption ionization source, octopole ion guides,
      external octopole ion trap capable of an axial potential gradient for ion
      ejection, capacitively coupled open cylindrical ion trap, and pulsed gas valve
      for ion cooling. Model compound responses with regard to various source and
      instrument conditions provide a basis for interpretation of broadband mass
      spectra of complex mixtures. As an example, we demonstrate broadband speciation
      of a Gulf Coast crude oil, with respect to numerous heteroatomic classes,
      compound types (rings plus double bonds), and carbon number distributions.

PMID- 15732914
TI  - Deep UV laser-induced fluorescence detection of unlabeled drugs and proteins in
      microchip electrophoresis.
AB  - Deep UV fluorescence detection at 266-nm excitation wavelength has been realized
      for sensitive detection in microchip electrophoresis. For this purpose, an
      epifluorescence setup was developed enabling the coupling of a deep UV laser into
      a commercial fluorescence microscope. Deep UV laser excitation utilizing a
      frequency quadrupled pulsed laser operating at 266 nm shows an impressive
      performance for native fluorescence detection of various compounds in fused
      silica microfluidic devices. Aromatic low molecular weight compounds such as
      serotonin, propranolol, a diol, and tryptophan could be detected at low
      micromolar concentrations. Deep UV fluorescence detection was also successfully
      employed for the detection of unlabeled basic proteins. For this purpose, fused
      silica chips dynamically coated with hydroxypropylmethyl cellulose were employed
      to suppress analyte adsorption. Utilizing fused-silica chips permanently coated
      with poly(vinyl alcohol), it was also possible to separate and detect egg white
      chicken proteins. These data show that deep UV fluorescence detection
      significantly widens the application range of fluorescence detection in chip
      based analysis techniques.

PMID- 15732915
TI  - High-throughput nanoliter sample introduction microfluidic chip-based flow
      injection analysis system with gravity-driven flows.
AB  - In this work, a simple, robust, and automated microfluidic chip-based FIA system
      with gravity-driven flows and liquid-core waveguide (LCW) spectrometric detection
      was developed. The high-throughput sample introduction system was composed of a
      capillary sampling probe and an array of horizontally positioned microsample
      vials with a slot fabricated on the bottom of each vial. FI sample loading and
      injection were performed by linearly moving the array of vials filled alternately
      with 50-microL samples and carrier, allowing the probe inlet to enter the
      solutions in the vials through the slots sequentially and the sample and carrier
      solution to be introduced into the chip driven by gravity. The performance of the
      system was demonstrated using the complexation of o-phenanthroline with Fe(II) as
      a model reaction. A 20-mm-long Teflon AF 2400 capillary (50-microm i.d., 375
      microm o.d.) was connected to the chip to function as a LCW detection flow cell
      with a cell volume of 40 nL and effective path length of 1.7 cm. Linear
      absorbance response was obtained in the range of 1.0-100 microM Fe(II)
      (r2=0.9967), and a good reproducibility of 0.6% RSD (n=18) was achieved. The
      sensitivity was comparable with that obtained using conventional FIA systems,
      which typically consume 10,000-fold more sample. The highest sampling throughput
      of 1000 h-1 was obtained by using injection times of 0.08 and 3.4 s for sample
      and carrier solution, respectively, with a sample consumption of only 0.6 nL for
      each cycle.

PMID- 15732916
TI  - Magnetic resonance microimaging and numerical simulations of velocity fields
      inside enlarged flow cells used for coupled NMR microseparations.
AB  - The coupling of various chemical microseparation methods with small-scale NMR
      detection is a growing area in analytical chemistry. The formation of enlarged
      flow cells within the active volume of the NMR detector can significantly
      increase the coil filling factor and hence the signal-to-noise ratio of the NMR
      spectra. However, flow cells can also lead to deterioration of the separation
      efficiency due to the development of complex flow patterns, the form of which
      depend on the particular geometry of the flow cell and the flow rate used. In
      this study, we investigated the flow characteristics in different flow cell
      geometries relevant to the coupling of capillary liquid chromatography and NMR.
      Computational fluid dynamics was used to simulate fluid flow inside flow cells
      with a volume of approximately 1 microL. Magnetic resonance microimaging was used
      to measure experimentally the velocity fields inside these flow cells. The
      results showed good agreement between experiment and simulation and demonstrated
      that a relatively gradual expansion and contraction is necessary to avoid areas
      of weak recirculation and strong radial velocities, both of which can potentially
      compromise separation efficiency.

PMID- 15732918
TI  - GC/MS profiling of gamma-hydroxybutyrate and precursors in various animal tissues
      using automatic solid-phase extraction. Preliminary investigations of its
      potential interest in postmortem interval determination.
AB  - To quantify gamma-hydroxybutyrate (GHB) and its physiological metabolites, gamma
      aminobutyric acid (GABA), 1,4-butanediol (1,4-BD), and gamma-butyrolactone (GBL)
      in various animal tissues (kidney, muscle, heart, liver, blood, brain cortex,
      thalamus, hypothalamus, hippocampus, or pons), an original gas
      chromatographic/mass spectrometric method with a automated solid-phase extraction
      by Oasis MCX cartridges on a Gilson Aspec Xli was developed. Using such apparatus
      allowed the limit of detection (LOD) of target compounds to be significantly
      lowered (LOD: 0.027, 0.025, and 5.7 microg/mL for GHB, 1,4-BD, and GABA,
      respectively, in 200 microL or microg of sample). After validation of each
      analytical step, the satisfactory performances of the apparatus in conjunction
      with the rapidity and ease of the extraction step make it suitable for
      simultaneous assay of GHB, 1,4-BD, GBL, and GABA. The method was used to test the
      correlation between GHB levels in tissues obtained at different times after death
      of male Sprague-Dawley rats and the postmortem interval. Preliminary results show
      a linear increase of GHB levels in relation to time of death in thoracic blood
      and central nervous system of animals kept at 15 and 20 degrees C.

PMID- 15732917
TI  - High-throughput solution-based medicinal library screening against human serum
      albumin.
AB  - High-throughput screening of combinatorial libraries has evolved from studying
      large diverse libraries to analyzing small, structurally similar, focused
      libraries. This paradigm shift has generated a need for rapid screening
      technologies to screen both diverse and focused libraries in a simple, efficient,
      and inexpensive manner. We have proactively addressed these needs by developing a
      high-throughput, solution-based method combining size exclusion (SEC), two
      dimensional liquid chromatography (2-D LC), and mass spectrometry (MS) for
      determining the relative binding of drug candidates in small, focused medicinal
      libraries against human serum albumin (HSA). Two types of libraries were used to
      evaluate the performance of the system. The first consisted of five diverse
      ligands with a wide range of hydrophobicities and whose association constants to
      HSA cover 3 orders of magnitude. A beta-lactam library composed of structurally
      similar compounds was used to further confirm the validity of the methodology.
      The ability to distinguish site-specific interactions of drugs competing for
      individual domains of the HSA receptor is also demonstrated. Comparison of
      chromatographic profiles of the library components before and after incubation
      with the receptor using multiple reaction monitoring allowed a ranking of the
      ligands according to their relative binding affinities. The observed rankings
      correlate closely with literature values of the association constants between the
      respective ligands and HSA. This simple, rugged methodology can screen a wide
      spectrum of chemical entities from combinatorial mixtures in less than 6 min.

PMID- 15732919
TI  - Evaluating enzymes that generate genotoxic benzo[a]pyrene metabolites using
      sensor arrays.
AB  - Arrays with individually addressable, demountable electrodes coated with
      ultrathin DNA/enzyme films were evaluated to estimate relative rates of genotoxic
      bioactivation of benzo[a]pyrene (BP) for several different enzymes
      simultaneously. Specifically, cytochrome (cyt) P450cam, cyt P40 1A2, and
      myoglobin in the array were activated with H2O2 to metabolize BP to genotoxic
      metabolites. DNA damage by the metabolites was detected by increases in square
      wave voltammetric oxidation peaks using Ru(bpy)3(2+) as catalyst. Cyt P450cam and
      cyt P450 1A2 showed 3-fold higher activity for genotoxic bioactivation of BP than
      myoglobin. The ability of the arrays to generate and detect metabolite-based DNA
      damage simultaneously for several enzymes is a rapid and promising approach to
      identify and characterize enzymes involved in genotoxicity of drugs and
      pollutants.

PMID- 15732921
TI  - Correction of temperature-induced spectral variations by loading space
      standardization.
AB  - With a view to maintaining the validity of multivariate calibration models for
      chemical processes affected by temperature fluctuations, loading space
      standardization (LSS) is proposed. Through the application of LSS, multivariate
      calibration models built at temperatures other than those of the test samples can
      provide predictions with an accuracy comparable to the results obtained at a
      constant temperature. Compared with other methods, designed for the same purpose,
      such as continuous piecewise direct standardization, LSS has the advantages of
      straightforward implementation and good performance. The methodology was applied
      to shortwave NIR spectral data sets measured at different temperatures. The
      results showed that LSS can effectively remove the influence of temperature
      variations on the spectra and maintain the predictive abilities of the
      multivariate calibration models.

PMID- 15732920
TI  - Correlation coefficient mapping in fluorescence spectroscopy: tissue
      classification for cancer detection.
AB  - Correlation coefficient mapping has been applied to intrinsic fluorescence
      spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence
      emission spectra were collected of 57 colonic tissue sites in a range of 4
      physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and
      cancerous tissues (21). The sample-sample correlation was used to examine the
      ability of correlation coefficient mapping to determine tissue disease state. The
      correlation coefficient map indicates two main categories of samples. These
      categories were found to relate to disease states of the tissue. Sensitivity,
      selectivity, predictive value positive, and predictive value negative for
      differentiation between normal tissue and all other categories were all above
      92%. This was found to be similar to, or higher than, tissue classification using
      existing methods of data reduction. Wavelength-wavelength correlation among the
      samples highlights areas of importance for tissue classification. The two
      dimensional correlation map reveals absorption by NADH and hemoglobin in the
      samples as negative correlation, an effect not obvious from the one-dimensional
      fluorescence spectra alone. The integrity of tissue was examined in a time series
      of spectra of a single tissue sample taken after tissue resection. The wavelength
      wavelength correlation coefficient map shows the areas of significance for each
      fluorophore and their relation to each other. NADH displays negative correlation
      to collagen and FAD, from the absorption of emission or fluorescence resonance
      energy transfer. The wavelength-wavelength correlation map for the decay set also
      clearly shows that there are only three fluorophores of importance in the
      samples, by the well-defined pattern of the map. The sample-sample correlation
      coefficient map reveals the changes over time and their impact on tissue
      classification. Correlation coefficient mapping proves to be an effective method
      for sample classification and cancer detection.

PMID- 15732922
TI  - Ion-molecule reactions for the characterization of polyols and polyol mixtures by
      ESI/FT-ICR mass spectrometry.
AB  - A mass spectrometric method is described for the identification and counting of
      hydroxyl groups in an analyte. Analytes introduced into a FT-ICR mass
      spectrometer and ionized by positive mode ESI were allowed to react with the
      neutral reagent diethylmethoxyborane. This results in derivatization of the
      hydroxyl groups of the analytes by replacement of a proton with a diethylborenium
      ion. Protonated polyols react by consecutive derivatization reactions, wherein
      all, or nearly all, of the hydroxyls are derivatized. The polyol derivatization
      products are separated by 68 mass units in the mass spectrum. This 68 Da mass
      shift, along with 30 Da mass shifts arising from intramolecular derivatization of
      the primary derivatization products, makes it easy to count the number of
      functional groups present in the analyte. The utility of this method for the
      analysis of polyols as single-component solutions, as mixtures, or in HPLC
      effluent (LC-MS analysis) is demonstrated.

PMID- 15732923
TI  - Application of flow field flow fractionation-ICPMS for the study of uranium
      binding in bacterial cell suspensions.
AB  - Field flow fractionation (FFF) is a size-based separation technique applicable to
      biomolecules, colloids, and bacteria in solution. When interfaced with ICPMS on
      line, elemental data can be collected concurrent with size distribution. We
      employed hyperlayer flow FFF (Fl FFF) methodology to separate cells of Shewanella
      oneidensis strain MR-1 from exopolymers present in washed cell suspensions. With
      a channel flow of 4 mL min-1 and a cross-flow of 0.4 mL min-1 cells eluted with a
      retention time of 4.7 min corresponding to an approximate equivalent spherical
      cell diameter of 0.8 microm. Cell suspensions were amended with increasing
      concentrations of U to establish an adsorption isotherm and with fixed U
      concentrations at varying pH to establish the pH dependence of sorption. A linear
      sorption isotherm was determined for U solution concentrations of 0.2-16 microM,
      maximum U sorption occurred at pH 5. A high molecular weight compound, presumably
      a cell exudate, was identified by Fl FFF-ICPMS. This cell exudate complexed U,
      and at elevated pH, the exudate appeared to have a greater affinity for U than
      cell surfaces. Thus, Fl FFF interfaced with ICPMS detection is a powerful
      analytical technique for metal sorption studies with bacteria; analysis can be
      carried out on small sample volumes (25 microL) and additional speciation
      information can be gained because of the versatile Fl FFF separation range and
      multielement detection capabilities of ICPMS.

PMID- 15732925
TI  - Behavior of bacteria in the inductively coupled plasma: atomization and
      production of atomic ions for mass spectrometry.
AB  - The combination of perfusion chromatography (PC) and inductively coupled plasma
      mass spectrometry (ICPMS) is a fast, general way to monitor metal incorporation
      into bacteria. U+ signals from U incorporated intrinsically in Bacillus subtilis
      (B. subtilis) are measured with 4 ms time resolution to investigate the behavior
      of individual cells in the ICP. When intact B. subtilis cells are introduced
      directly into the ICP, occasional U+ spikes are observed. The positive U+ spikes
      suggest that bacteria behave more like solid particles than wet droplets in the
      ICP, compared to previous studies of such transient effects in the ICP. Drying
      the bacterial aerosol does not eliminate the spikes. Lysing the bacteria by
      sonication increases the U+ response by 30% compared to that from the untreated
      sample. PC results from a 10 ppb U standard, partially lysed and fully lysed
      bacteria samples show that the intracellular U-bound species are released by
      sonication and are small in size. The atomization-ionization efficiencies for
      different elements (U, Ca, and Mg) from cells differ somewhat. Reducing the
      aerosol gas flow rate by 0.1 L min-1 improves the relative U+ response for
      unlysed bacteria to 85% of that for lysed cells, although the absolute U+ signal
      is attenuated greatly.

PMID- 15732926
TI  - Sol-gel modified poly(dimethylsiloxane) microfluidic devices with high
      electroosmotic mobilities and hydrophilic channel wall characteristics.
AB  - Using a sol-gel method, we have fabricated poly(dimethylsiloxane) (PDMS)
      microchips with SiO2 particles homogeneously distributed within the PDMS polymer
      matrix. These particles are approximately 10 nm in diameter. To fabricate such
      devices, PDMS (Sylgard 184) was cast against SU-8 molds. After curing, the chips
      were carefully removed from the mold and sealed against flat, cured pieces of
      PDMS to form enclosed channel manifolds. These chips were then solvated in
      tetraethyl orthosilicate (TEOS), causing them to expand. Subsequently, the chips
      were placed in an aqueous solution containing 2.8% ethylamine and heated to form
      nanometer-sized SiO2 particles within the cross-linked PDMS polymer. The water
      contact angle for the PDMS-SiO2 chips was approximately 90.2 degrees compared to
      a water contact angle for Sylgard 184 of approximately 108.5 degrees . More
      importantly, the SiO2 modified PDMS chips showed no rhodamine B absorption after
      4 h, indicating a substantially more hydrophilic and nonabsorptive surface than
      native PDMS. Initial electroosmotic mobilities (EOM) of (8.3+/-0.2)x10(-4)
      cm2/(V.s) (RSD=2.6% (RSD is relative standard deviation); n=10) were measured.
      This value was approximately twice that of native Sylgard 184 PDMS chips (4.21+/
      0.09)x10(-4) cm2/(V.s) (RSD=2.2%; n=10) and 55% greater than glass chips (5.3+/
      0.4)x10(-4) cm2/(V.s) (RSD=7.7%; n=5). After 60 days of dry storage, the EOM was
      (7.6+/-0.3)x10(-4) cm2/(V.s) (RSD=3.9%; n=3), a decrease of only 8% below that of
      the initially measured value. Separations performed on these devices generated
      80,000-100,000 theoretical plates in 6-14 s for both tetramethylrhodamine
      succidimidyl ester and fluorescein-5-isothiocyanate derivatized amino acids. The
      separation distance was 3.5 cm. Plots of peak variance vs analyte migration times
      gave diffusion coefficients which indicate that the separation efficiencies are
      within 15% of the diffusion limit.

PMID- 15732924
TI  - Incorporation of single-wall carbon nanotubes into an organic polymer monolithic
      stationary phase for mu-HPLC and capillary electrochromatography.
AB  - Single-wall carbon nanotubes (SWNT) were incorporated into an organic polymer
      monolith containing vinylbenzyl chloride (VBC) and ethylene dimethacrylate (EDMA)
      to form a novel monolithic stationary phase for high-performance liquid
      chromatography (HPLC) and capillary electrochromatography (CEC). The retention
      behavior of neutral compounds on this poly(VBC-EDMA-SWNT) monolith was examined
      by separating a mixture of small organic molecules using micro-HPLC. The result
      indicated that incorporation of SWNT enhanced chromatographic retention of small
      neutral molecules in reversed-phase HPLC presumably because of their strongly
      hydrophobic characteristics. The stationary phase was formed inside a fused
      silica capillary whose lumen was coated with covalently bound polyethyleneimine
      (PEI). The annular electroosmotic flow (EOF) generated by the PEI coating allowed
      peptide separation by CEC in the counterdirectional mode. Comparison of peptide
      separations on poly(VBC-EDMA-SWNT) and on poly(VBC-EDMA) with annular EOF
      generation revealed that the incorporation of SWNT into the monolithic stationary
      phase improved peak efficiency and influenced chromatographic retention. The
      structures of pretreated SWNT and poly(VBC-EDMA-SWNT) monolith were examined by
      high-resolution transmission electron microscopy, Raman spectroscopy, scanning
      electron microscopy, and multipoint BET nitrogen adsorption/desorption.

PMID- 15732927
TI  - Boosting partial least squares.
AB  - A difficulty when applying partial least squares (PLS) in multivariate
      calibration is that overfitting may occur. This study proposes a novel approach
      by combining PLS and boosting. The latter is said to be resistant to overfitting.
      The proposed method, called boosting PLS (BPLS), combines a set of shrunken PLS
      models, each with only one PLS component. The method is iterative: the models are
      constructed on the basis of the residuals of the responses that are not explained
      by previous models. Unlike classical PLS, BPLS does not need to select an
      adequate number of PLS components to be included in the model. On the other hand,
      two parameters must be determined: the shrinkage value and the iteration number.
      Criteria are proposed for these two purposes. BPLS was applied to seven real data
      sets, and the results demonstrate that it is more resistant than classical PLS to
      overfitting without loosing accuracy.

PMID- 15732928
TI  - In vivo deamidation characterization of monoclonal antibody by LC/MS/MS.
AB  - The spontaneous nonenzymatic deamidation of glutaminyl and asparaginyl residues
      of peptides and proteins has been observed both in vitro and in vivo. Deamidation
      may change the structure and function of a peptide or protein, potentially
      resulting in decreased bioactivity, as well as alterations in pharmacokinetics
      and antigenicity of the protein pharmaceutical. Therefore, it is necessary to
      monitor the effect of storage and formulation conditions on deamidation of a
      protein drug candidate. Of particular interest is the investigation of in vivo
      deamidation mechanisms of protein drug candidates. Several methods are available
      to characterize the deamidation of peptides and proteins. We present here a
      LC/MS/MS method used to evaluate the deamidation of an antibody after in vivo
      administration. A humanized monoclonal IgG1 antibody (MAb) has several "hot
      spots" for spontaneous deamidation. One site, amino acid residue Asn55 located in
      the CDR2 region of the heavy chain, is of particular interest since deamidation
      at this site greatly decreases the binding activity. MAb was administered to
      cynomolgus monkeys by intravenous and subcutaneous routes. At various times after
      dosing, monkey serum was prepared and MAb captured by the immobilized antigen or
      a goat anti-human IgG Fcgamma antibody. The captured MAb was treated with trypsin
      followed by endoproteinase Glu-C. The digests were separated on RP-HPLC and
      analyzed by MS/MS on Q-Tof Global mass spectrometer. Using this method, we were
      able to determine the deamidation half-life of amino acid residue Asn55 in vivo
      and the ratio of the deamidated derivatives, i.e., isoAsp55 and Asp55. The method
      is rapid and sensitive with low-nanogram quantities of protein detected in the
      biological matrix.

PMID- 15732929
TI  - Direct determination of dibenzo[a,l]pyrene and its four dibenzopyrene isomers in
      water samples by solid-liquid extraction and laser-excited time-resolved
      Shpol'skii spectrometry.
AB  - Dibenzo[a,l]pyrene is considered the most potent carcinogen of all polycyclic
      aromatic hydrocarbons ever tested. Its four isomers, which include
      dibenzo[a,e]pyrene, dibenzo[a,h]pyrene, dibenzo[a,i]pyrene, and
      dibenzo[e,l]pyrene, are also carcinogenic and, therefore, a potential threat to
      humans. The method presented here provides a direct way for their determination
      in water samples. The entire procedure--from water extraction to LETRSS analysis-
      takes less than 15 min/sample and it consumes only 100 microL of organic solvent.
      This fact makes our approach environmentally friendly and cost-effective.
      Unambiguous isomer determination is accomplished via multidimensional data
      formats, namely, wavelength time matrixes, excitation-emission matrixes, and time
      resolved excitation-emission matrixes. The analytical figures of merit
      demonstrate precise and accurate analysis at the sub-parts-per-billion level.
      Limits of detection are at the parts-per-trillion level. The potential of this
      approach for real-world analysis is illustrated with a heavily contaminated water
      samples.

PMID- 15732931
TI  - Approach for determining protein ubiquitination sites by MALDI-TOF mass
      spectrometry.
AB  - Protein ubiquitination plays an important role in the degradation and other
      functional regulation of cellular proteins in organisms ranging from yeasts to
      mammals. Trypsin digestion of ubiquitin conjugated proteins produces diglycine
      branched peptides in which the C-terminal Gly-Gly fragment of ubiquitin is
      attached to the epsilon-amino group of a modified lysine residue within the
      peptide. This provides a platform for mapping ubiquitination sites using mass
      spectrometry. Here we report the development of a novel strategy for determining
      posttraslational protein ubiquitination based on the N-terminal sulfonation of
      diglycine branched peptides. In contrast to conventional tandem MS spectra of
      native tryptic peptides, MALDI MS/MS analysis of a sulfonated tryptic peptide
      containing a diglycine branch generates a unique spectrum composed of a signature
      portion and a sequence portion. The signature portion of the spectrum consists of
      several intense ions resulting from the elimination of the tags, the N-terminal
      residues at the peptide and the branch, and their combination. This unique ion
      distribution pattern can distinguish ubiquitination modificatons from others and
      can identify the first N-terminal residues of the peptides as well. The sequence
      portion consists of an exclusive series of y-type ions and y' ions (differing by
      the loss of one glycine residue from the sulfonated diglycine branch) that can
      directly reveal the amino acid sequence of the peptide and the precise location
      of the ubiquitination site. The technique is demonstrated for a series of
      synthetic peptides and is validated by a model protein, tetraubiquitin. Our
      results show that the MALDI MS/MS analysis of sulfonated tryptic peptides can
      provide a highly effective method for the determination of ubiquitination
      substrates, ubiquitination sites on protein targets, and modification sites on
      ubiquitins themselves.

PMID- 15732930
TI  - Strategy for the isolation, derivatization, chromatographic separation, and
      detection of carnitine and acylcarnitines.
AB  - A strategy for detection of carnitine and acylcarnitines is introduced. This
      versatile system has four components: (1) isolation by protein
      precipitation/desalting and cation-exchange solid-phase extraction, (2)
      derivatization of carnitine and acylcarnitines with pentafluorophenacyl
      trifluoromethanesulfonate, (3) sequential ion-exchange/reversed-phase
      chromatography using a single non-end-capped C8 column, and (4) detection of
      carnitine and acylcarnitine pentafluorophenacyl esters using an ion trap mass
      spectrometer. Recovery of carnitine and acylcarnitines from the isolation
      procedure is 77-85%. Derivatization is rapid and complete with no evidence of
      acylcarnitine hydrolysis. Sequential ion-exchange/reversed-phase HPLC results in
      separation of reagent byproducts from derivatized carnitine and acylcarnitines,
      followed by reversed-phase separation of carnitine and acylcarnitine
      pentafluorophenacyl esters. Detection by MS/MS is highly selective, with
      carnitine pentafluorophenacyl ester yielding a strong product ion at m/z 311 and
      acylcarnitine pentafluorophenacyl ester fragmentation yielding two product ions:
      (1) loss of m/z 59 and (2) generation of an ion at m/z 293. To demonstrate this
      analytical strategy, phosphate buffered serum albumin was spiked with carnitine
      and 15 acylcarnitines and analyzed using the described protein
      precipitation/desalting and cation-exchange solid-phase extraction isolation,
      derivatization with pentafluorophenacyl trifluoromethanesulfonate, chromatography
      using the sequential ion-exchange/reversed-phase chromatography HPLC system, and
      detection by MS and MS/MS. Successful application of this strategy to the
      quantification of carnitine and acetylcarnitine in rat liver is shown.

PMID- 15732932
TI  - Mass spectrometer characterization of halogen gases in air at atmospheric
      pressure.
AB  - We have developed a new interface for a commercial ion trap mass spectrometer
      equipped with APCI capable of real-time measurements of gaseous compounds with
      limits of detection on the order of pptv. The new interface has been tested using
      the detection of Br2 and Cl2 over synthetic seawater ice at atmospheric pressure
      as a model system. A mechanical pump is used to draw gaseous mixtures through a
      glass manifold into the corona discharge area, where the molecules are ionized.
      Analysis of bromine and chlorine in dry air show that ion intensity is affected
      by the pumping rate and the position of the glass manifold. The mass spectrometer
      signals for Br2 are linear in the 0.1-10.6 ppbv range, and the estimated 3sigma
      detection limit is 20 pptv. The MS signals for Cl2 are linear in the 0.2-25 ppbv
      range, and the estimated 3sigma detection limit is 1 ppbv. This new interface
      advances the field of analytical chemistry by introducing a practical
      modification to a commercially available ion trap mass spectrometer that expands
      the available methods for performing highly specific and sensitive measurements
      of gases in air at atmospheric pressure.

PMID- 15732934
TI  - Homogeneous assay based on anti-Stokes' shift time-resolved fluorescence
      resonance energy-transfer measurement.
AB  - We report here a novel, time-resolved, lanthanide-based energy-transfer assay
      utilizing nonoverlapping acceptor fluorophores, which have their absorption
      energetically at a higher level than the emittive transitions of the donor. The
      technique was studied by comparing a series of nonoverlapping acceptors in a
      homogeneous DNA model assay utilizing Eu3+ chelate as a donor. The assay provides
      strong energy-transfer enhanced acceptor emission and enables the anti-Stokes'
      shift FRET measurement, in which the induced acceptor emission is at shorter
      wavelength than the donor emission. This results in high sensitivity, and 0.8 pM
      detection limit was measured for the DNA target. The acceptor signal of the assay
      is characterized by exceptional lifetime properties and is not strictly following
      the Forster's theory. The mechanism of nonoverlapping energy transfer is
      considered, and we propose that when nonoverlapping acceptors are utilized, the
      energy transfer arises from the upper 5D2 and 5D1 excited states of europium. The
      assumption was studied using a simplified energy level scheme of the Eu3+ donor
      and the acceptors, and a correlation between the acceptor emission behavior and
      the energy level scheme was found.

PMID- 15732933
TI  - Confirmatory and quantitative analysis of beta-lactam antibiotics in bovine
      kidney tissue by dispersive solid-phase extraction and liquid chromatography
      tandem mass spectrometry.
AB  - A simple, rapid, rugged, sensitive, and specific method for the confirmation and
      quantitation of 10 beta-lactam antibiotics in fortified and incurred bovine
      kidney tissue has been developed. The method uses a simple solvent extraction,
      dispersive solid-phase extraction (dispersive-SPE) cleanup, and liquid
      chromatography-tandem mass spectrometry (LC/MS/MS) for confirmation and
      quantitation. Dispersive-SPE greatly simplifies and accelerates sample cleanup
      and improves overall recoveries compared with conventional SPE cleanup. The beta
      lactam antibiotics tested were as follows: deacetylcephapirin (an antimicrobial
      metabolite of cephapirin), amoxicillin, desfuroylceftiofur cysteine disulfide
      (DCCD, an antimicrobial metabolite of ceftiofur), ampicillin, cefazolin,
      penicillin G, oxacillin, cloxacillin, naficillin, and dicloxacillin. Average
      recoveries of fortified samples were 70% or better for all beta-lactams except
      DCCD, which had an average recovery of 58%. The LC/MS/MS method was able to
      demonstrate quantitative recoveries at established tolerance levels and provide
      confirmatory data for unambiguous analyte identification. The method was also
      tested on 30 incurred bovine kidney samples obtained from the USDA Food Safety
      and Inspection Service, which had previously tested the samples using the
      approved semiquantitative microbial assay. The results from the quantitative
      LC/MS/MS analysis were in general agreement with the microbial assay for 23
      samples although the LC/MS/MS method was superior in that it could specifically
      identify which beta-lactam was present and quantitate its concentration, whereas
      the microbial assay could only identify the type of beta-lactam present and
      report a concentration with respect to the microbial inhibition of a penicillin G
      standard. In addition, for 6 of the 23 samples, LC/MS/MS analysis detected a
      penicillin and a cephalosporin beta-lactam, whereas the microbial assay detected
      only a penicillin beta-lactam. For samples that do not fall into the "general
      agreement" category, the most serious discrepancy involves two samples where the
      LC/MS/MS method detected a violative level of a cephalosporin beta-lactam
      (deacetylcephapirin) in the first sample and a possibly violative level of
      desfuroylceftiofur in the second, whereas the microbial assay identified the two
      samples as having only violative levels of a penicillin beta-lactam.

PMID- 15732935
TI  - Identification of microbial mixtures by capillary electrophoresis/selective
      tandem mass spectrometry.
AB  - In this paper, we propose a new strategy for identifying specific bacteria in
      bacterial mixtures by using CE-selective MS/MS of peptide marker ions associated
      with the bacteria of interest. We searched the CE-MS/MS spectra acquired from the
      proteolytic digests of pure bacterial cell extracts against protein databases.
      The identified peptides that match the protein associated with the corresponding
      species were selected as marker ions for bacterial identification. Specific
      peptide marker ions were obtained for each of the following three pathogens:
      Pseudomonas aeruginasa, Staphylococcus aureus, and Staphylococcus epidermidis. To
      identify a bacterial species in a sample, we performed CE-MS/MS analysis of the
      selected marker ions in the proteolytic digest of the cell extract and then
      performed protein database searches. The selected peptides that we identified
      correctly from Xcorr values ranking at the top of the search results allowed us
      to identify the corresponding bacterial species present in the sample. We have
      applied this method successfully to the identification of various mixtures of the
      three pathogens. Even minor bacterial species present at a concentration of 1%
      can be identified with great confidence. This method for CE-MS/MS analysis of
      bacteria-specific marker peptides provides excellent selectivity and high
      accuracy when identifying bacterial species in complex systems. In addition, we
      have used this approach to identify P. aeruginasa in a saliva sample spiked with
      E.coli and P. aeruginasa.

PMID- 15732937
TI  - Method for trace level analysis of C8, C9, C10, C11, and C13 perfluorocarbon
      carboxylic acids in water.
AB  - A method was developed for the trace level analysis of pentadecafluorooctanoic
      acid (C8), heptadecafluorononanoic acid (C9), nonadecafluorodecanoic acid (C10),
      heneicosafluoroundecanoic acid (C11) and pentacosafluorotridecanoic acid (C13) in
      water. Samples were concentrated by solid-phase extraction (SPE) before analysis
      by combined liquid chromatography/electrospray tandem mass spectrometry
      (LC/MS/MS). A surrogate standard, 9-hydrohexadecafluorononanoic acid (9H), was
      used to monitor recovery. The lower limit of quantitation (LLOQ) for C8, C9, C10,
      C11, and C13 was determined to be 25 ng/L in water. The specificity of the method
      was established by showing no significant interferences (<20% of the LLOQ
      standard) in control samples of well, stream, spring, tap, omnisolve, and type I
      water at the retention time of the target analytes. The linearity of the method
      was determined; the coefficients of determination for the five calibration curves
      generated were all >0.985. Good within-day and between-day accuracy and precision
      were demonstrated. Extracts and standards were shown to be stable after remaining
      at room temperature for approximately 24 h. Samples fortified with C8, C9, C10,
      and C11 were shown to be stable after remaining at room temperature for 14 days
      before extraction. Samples fortified with C13 were shown to be stable after
      remaining at room temperature for 7 days before extraction. Fortified samples,
      extracts, and standards demonstrated stability after being stored in a
      refrigerator for 14 days for all analytes. Long-term storage stability was
      demonstrated for methanolic stock solutions.

PMID- 15732936
TI  - Electrochemical immunosensors for the simultaneous detection of two tumor
      markers.
AB  - The microfabrication of electrochemical immunosensors for the simultaneous
      detection of two protein analytes is described. The sensors consisted of two
      iridium oxide electrodes (1-mm diameter) patterned on a glass substrate. Capture
      antibodies were immobilized on the porous iridium oxide electrodes by covalent
      attachment using (3-aminopropyl)triethoxysilane and glutaraldehyde. The spatial
      separation of the electrodes (2.5 mm) enabled simultaneous electrochemical
      immunoassays to be conducted without cross-talk between the electrodes. Proteins
      were measured using electrochemical ELISA, and detection was achieved by
      electrochemically oxidizing alkaline phosphatase-generated hydroquinone. Sensors
      for the simultaneous detection of goat IgG and mouse IgG, and for the tumor
      markers CEA and AFP, were developed. The sensors had detection limits of 1, 2,
      1.2, and 1 ng/mL for goat IgG, mouse IgG, CEA, and AFP, respectively.

PMID- 15732938
TI  - Toxin screening in phytoplankton: detection and quantitation using MALDI triple
      quadrupole mass spectrometry.
AB  - The investigation of a MALDI triple quadrupole instrument for the analysis of
      spirolide toxins in phytoplankton samples is described in this study. A high
      frequency (kHz) laser was employed for MALDI, generating a semicontinuous ion
      beam, thus taking advantage of the high duty cycle obtained in sensitive triple
      quadrupole MRM experiments. Initially, several experimental parameters such as
      type of organic matrix and concentration, solvent composition, and matrix-to
      analyte ratio were optimized, and their impact on sensitivity and precision of
      the obtained ion currents for a reference spirolide, 13-desmethyl-C, was studied.
      In all quantitative experiments, excellent linearities in the concentration range
      between 0.01 and 1.75 microg/mL were obtained, with R2 values of 0.99 or higher.
      The average precision of the quantitative MALDI measurements was 7.4+/-2.4% RSD.
      No systematic errors were apparent with this method as shown by a direct
      comparison to an electrospray LC/MS/MS method. Most importantly, the MALDI
      technique was very fast; each sample spot was analyzed in less than 5 s as
      compared to several minutes with the electrospray assay. To demonstrate the
      potential of the MALDI triple quadrupole method, its application to quantitative
      analysis in several different phytoplankton samples was investigated, including
      crude extracts and samples from mass-triggered fractionation experiments. 13
      Desmethyl spirolide C was successfully quantified in these complex samples at
      concentration levels from 0.05 to 90.4 microg/mL (prior to dilution to have
      samples fall within the dynamic range of the method) without extensive sample
      preparation steps. The versatility of the MALDI triple quadrupole method was also
      exhibited for the identification of unknown spirolide analogues. Through the use
      of dedicated linked scan functions such as precursor ion and neutral loss scans,
      several spirolide compounds were tentatively identified directly from the crude
      extract, without the usual time-consuming chromatographic preseparation steps.
      Moreover, high-quality CID spectra were obtained for low-abundant spirolides
      present in the phytoplankton samples.

PMID- 15732939
TI  - Development of a detector for liquid chromatography based on aerosol
      chemiluminescence on porous alumina.
AB  - This paper describes a novel aerosol chemiluminescence-based detector, which can
      be coupled to liquid chromatography for the determination of the chemicals with
      weak optical absorbance in the UV-visible region. This aerosol chemiluminescence
      (CL)-based detector, in which HPLC effluent is converted to aerosol and then
      generated CL emission on the surface of porous alumina, is composed of three main
      processes: nebulization of HPLC effluent, CL emission on surface of porous
      alumina material, and optical detection. To demonstrate the utility of the
      aerosol chemiluminescence detector, some compounds such saccharides,
      poly(ethylene glycol)s, amino acids, and steroid pharmaceuticals are determined
      by the present aerosol chemiluminescence detection method. Compared with an
      evaporative light scattering detector, the proposed detector shows the following
      features: (a) extensive CL emissions on porous alumina by many compounds tested,
      which leads to the potential application for the determination of volatile and
      nonvolatile chemicals with or without UV-visible absorbance; (b) a CL mechanism
      based on the catalytic oxidation of analytes, not on the light scattering, which
      suggests the present detector be free from the interference of the inorganic and
      nonvolatile mobile-phase modifiers. The CL characteristics and effect of
      different parameters, such as temperature and nebulizer gas flow rate, were also
      discussed in this paper. Furthermore, this aerosol chemiluminescence-based
      detector was successfully applied to the determination of raffinose, glucose,
      sucrose, maltose, and alpha-lactose.

PMID- 15732940
TI  - Thermochemistry of protein-DNA interaction studied with temperature-controlled
      nonequilibrium capillary electrophoresis of equilibrium mixtures.
AB  - We introduce temperature-controlled nonequilibrium capillary electrophoresis of
      equilibrium mixtures (NECEEM) and demonstrate its use to study thermochemistry of
      protein-DNA interactions. Being a homogeneous kinetic method, temperature
      controlled NECEEM uniquely allows finding temperature dependencies of equilibrium
      and kinetic parameters of complex formation without the immobilization of the
      interacting molecules on the surface of a solid substrate. In this work, we
      applied temperature-controlled NECEEM to study the thermochemistry of two protein
      DNA pairs: (i) Taq DNA polymerase with its DNA aptamer and (ii) E. coli single
      stranded DNA binding protein with a 20-base-long single-stranded DNA. We
      determined temperature dependencies of three parameters: the equilibrium binding
      constant (Kb), the rate constant of complex dissociation (k(off)), and the rate
      constant of complex formation (k(on)). The Kb(T) functions for both protein-DNA
      pairs had phase-transition-like points suggesting temperature-dependent
      conformational changes in structures of the interacting macromolecules.
      Temperature dependencies of k(on) and k(off) provided insights into how the
      conformational changes affected two opposite processes: binding and dissociation.
      Finally, thermodynamic parameters, DeltaH and DeltaS, for complex formation were
      found for different conformations. With its unique features and potential
      applicability to other macromolecular interactions, temperature-controlled NECEEM
      establishes a valuable addition to the arsenal of analytical methods used to
      study dynamic molecular complexes.

PMID- 15732941
TI  - Multivariate statistical analysis of concatenated time-of-flight secondary ion
      mass spectrometry spectral images. Complete description of the sample with one
      analysis.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) instruments are capable
      of saving an entire mass spectrum at each pixel of an image, allowing for
      retrospective analysis of masses that were not selected for analysis during data
      collection. These TOF-SIMS spectral images contain a wealth of information, but
      few tools are available to assist the analyst in visualizing the entire raw data
      set and as a result, most of the data are not analyzed. Automated, nonbiased,
      multivariate statistical analysis (MVSA) techniques are useful for converting the
      massive amount of data into a smaller number of chemical components (spectra and
      images) that are needed to fully describe the TOF-SIMS measurement. Many samples
      require two back-to-back TOF-SIMS measurements in order to fully characterize the
      sample, one measurement of the fraction of positively charged secondary ions
      (positive ion fraction) and one measurement of the fraction of negatively charged
      secondary ions (negative ion fraction). Each measurement then needs to be
      individually evaluated. In this paper, we report the first MVSA analysis of a
      concatenated TOF-SIMS data set comprising positive ion and negative ion spectral
      images collected on the same region of a sample. MVSA of concatenated data sets
      provides results that are intuitive and fully describe the sample. The analytical
      insight provided by MVSA of the concatenated data set was not obtained when
      either polarity data set was analyzed separately.

PMID- 15732942
TI  - Antitumor metallothiosemicarbazonates: structure and antitumor activity of
      palladium complex of phenanthrenequinone thiosemicarbazone.
AB  - The crystal structure of the potential antitumor metal compound, viz. chloro,
      mono(phenanthrenequinone thiosemicarbazonato) palladium(II) dimethyl formamide
      solvate, is reported. The central palladium(II) atom is in a square planar
      environment provided by the tridentate, monoanionic thiosemicarbazone ligand and
      the ancillary chloride ion. The compound exhibited remarkable activity against
      drug-sensitive and drug-resistant breast cancer cell lines and was relatively
      nontoxic toward the normal mammary epithelial cells. The drug-induced killing
      effect against breast cancer cell lines was predominantly mediated via apoptosis,
      a physiologic form of cell death.

PMID- 15732943
TI  - Synthesis and characterization of phenanthrylphosphine gold complex: observation
      of Au-induced blue-green phosphorescence at room temperature.
AB  - A new 9-diphenylphosphinophenanthrene ligand (9DPP, 1), its oxide (9DPPO, 2), and
      its gold complex [(AuCl(9DPP)] (3) were synthesized. The Au(I) complex 3 was
      found to exhibit intense blue-green, room-temperature phosphorescence (Phip =
      0.06 and tauT = 22.7 micros) originating in the locally excited triplet of the
      phenanthrene moiety (3LE) in degassed 2-methyltetrahydrofuran solution. On the
      assumption that PhiST = 1.0 for 3, the radiative rate constant (kr) in the
      triplet state is calculated to be 2.6 x 10(3) s(-1). This value is 4 orders of
      magnitude larger than the radiative rate constant of the triplet phenanthrene
      (0.26 s(-1)). Thus, the coordinated Au(I) atom is concluded to have a markedly
      large heavy-atom effect on kr of the phenanthrene chromophore in 3.

PMID- 15732944
TI  - Both nucleophile and substrate bind to the catalytic Fe(II)-center in the type-II
      methionyl aminopeptidase from Pyrococcus furiosus.
AB  - Metalloproteases utilize their active site divalent metal ions to generate a
      nucleophilic water/hydroxide. For methionine aminopeptidases (MetAPs), the exact
      location of this nucleophile, as well as of the substrate, with respect to the
      active site metal ion is unknown. In order to address this issue, we have
      examined the catalytically competent Fe(II)-loaded form of PfMetAP-II
      ([Fe(PfMetAP-II)]) in the absence and presence of both nitric oxide (NO) and the
      substrate-analogue inhibitor butaneboronic acid (BuBA) by kinetic and
      spectroscopic (EPR, UV-vis) methods. NO binds to [Fe(PfMetAP-II)] with a Kd of
      200 microM forming an {FeNO}7 complex. UV-vis spectra of the resulting
      [Fe(PfMetAP-II)]-NO complex indicate that the Fe(II) ion is six coordinate. These
      data suggest that NO binding occurs without displacing the bound aquo/hydroxo
      moiety in [Fe(PfMetAP-II)]. On the basis of EPR spectra, the resulting Fe-NO
      complex is best described as NO- (S = 1) antiferromagnetically coupled to a high
      spin Fe(III) ion (S = 5/2). The addition of BuBA to [Fe(PfMetAP-II)]-NO displaces
      the coordinated water molecule forming a six-coordinate adduct. EPR data also
      indicate that an interaction between the bound NO- and BuBA occurs forming a
      complex that mimics an intermediate step between the Michaelis complex and the
      tetrahedral transition-state.

PMID- 15732945
TI  - Unsupported gold(I)-copper(I) interactions through eta1 Au-[Au(C6F5)2]-
      coordination to Cu+ Lewis acid sites.
AB  - The reaction of the complex [Au2Ag2(C6F5)4)N[triple bond]CCH3)2]n (1) with 1
      equiv of CuCl in the presence of 1 equiv of pyrimidine ligand leads to the
      formation of the heteronuclear Au(I)-Cu(I) organometallic polymer
      [Cu{Au(C6F5)2}(N[triple bond]CCH3)(mu2-C4H4N2)]n (2) through a transmetalation
      reaction. Complex 2 displays unprecedented unsupported Au(I)...Cu(I) interactions
      of [Au(C6F5)2]- units with the acid Cu(I) sites in a [Cu(N[triple bond]CCH3)(mu2
      pyrimidine)]n+(n) polymeric chain. Complex 2 has a rich photophysics in solution
      and in the solid state.

PMID- 15732946
TI  - (C4N3H15)[(BO2)2(GeO2)4]: the first organically templated 3D borogermanate
      showing 1D 12-rings, large channels, and a novel zeolite-type framework topology
      constructed from Ge8O24 and B2O7 cluster units.
AB  - The first organically templated 3D borogermanate with a novel zeolite-type
      topology, (C4N3H15)[(BO2)2(GeO2)4] FJ-17, has been solvothermally synthesized and
      characterized by IR spectroscopy, powder X-ray diffraction (PXRD), TGA, and
      single-crystal X-ray diffraction. The compound crystallized in the monoclinic
      space group P2(1)/c with a = 6.967(1) A, b = 10.500(1) A, c = 20.501(1) A, beta =
      90.500(3) degrees , V = 1499.68(8) A3, and Z = 4. The framework topology of this
      compound is the previously unknown topology with the vertex symbols
      3.4.3.9.3.8(2) (vertex 1), 3.8.3.4.6(2).9(2) (vertex 2), 3.8(2).4.6(2).6(2).8
      (vertex 3), 4.8.4.8.8(3).12 (vertex 4), 4.8.4.8.8(2).12 (vertex 5), and
      3.8.4.6(2).6.8(2) (vertex 6). The structure is constructed from Ge8O24 and B2O7
      clusters. The Ge8O24 cluster contains eight GeO4 tetrahedra that share vertices;
      the B2O7 unit is composed of two BO4 tetrahedra sharing a vertex. The cyclic
      Ge8O24 clusters connect to each other through vertices to form a 2D layer with
      8,12-nets. The adjacent layers are further linked by the dimeric B2O7 cluster
      units, resulting in a 3D framework with 12- and 8-ring channels along the a and b
      axes, respectively. In addition, there is a unique B2GeO9 3-ring in the
      structure.

PMID- 15732948
TI  - Amide-ligand hydrogen bonding in reverse micelles.
AB  - One approach to modeling the second coordination shell of metalloproteins is to
      pair amide-containing counterions with metal complexes to form hydrogen bonds in
      the solid state. In a more general approach, we have designed a surfactant
      counterion that can sustain hydrogen bonding interactions with metal complexes in
      solution. The surfactant is cationic and incorporates an amide as part of its
      headgroup to form hydrogen. The surfactant forms hydrogen bonding reverse
      micelles that accommodate anionic metal complexes in their polar core. In reverse
      micelles containing an iron(III) hexacyanide complex, spectroscopic evidence
      suggests that the anion is confined to the polar core region in solution. Single
      crystal X-ray diffraction data on the surfactant ferricyanide system reveals a
      layered structure with interdigitated alkyl chains and an extensive network of
      hydrogen bonds that link amide groups to the cyanide ligands and to neighboring
      headgroups.

PMID- 15732947
TI  - Role of protons in superoxide reduction by a superoxide reductase analogue.
AB  - Superoxide reduction by thiolate-ligated [FeII(SMe2N4(tren))]+ (1) involves two
      proton-dependent steps and a single peroxide intermediate,
      [FeIII(SMe2N4(tren))(OOH)]+ (2). An external proton donor is required, ruling out
      mechanisms involving H+ or H-atom abstraction from the ligand N-H. The initial
      protonation step affording 2 occurs with fairly basic proton donors (EtOH, MeOH,
      NH4+) in THF. More acidic proton donors are required to cleave the Fe-O(peroxide)
      bond in MeOH, and this occurs via a dissociative mechanism. Reaction rates are
      dependent on the pKa of the proton donor, and a common
      [FeIII(SMe2N4(tren))(MeOH)]2+ (3) intermediate is involved. Acetic acid releases
      H2O2 from 2 under pseudo-first-order conditions ([HOAc] = 138 mM, [2] = 0.49 mM)
      with a rate constant of 8.2 x 10(-4) s(-1) at -78 degrees C in MeOH. Reduction of
      3 with Cp2Co regenerates the active catalyst 1.

PMID- 15732949
TI  - Transformation of inorganic sulfur into organic sulfur: a novel photoluminescent
      3-D polymeric complex involving ligands in situ formation.
AB  - The reaction of CuSCN with acetonitrile and methanol under solvothermal
      conditions yielded a novel 3-D polymeric photoluminescent complex containing
      dodecanuclear copper(I) clusters with methyl mercaptide. The synthesis involves
      in situ generation of ligands, which provides a model reaction to simulate the
      transformation of inorganic sulfur into organic sulfur under geothermic
      conditions.

PMID- 15732950
TI  - Self-assembly of homochiral porous solids based on 1D cadmium(II) coordination
      polymers.
AB  - A family of homochiral 1D cadmium(II) coordination polymers based on the (S)-2,2'
      dimethoxy-1,1'-binaphthyl-3,3'-bis(4-vinylpyridine) (L) bridging ligand were
      synthesized from the same building blocks under slightly different conditions,
      and characterized by single-crystal X-ray crystallography. While
      [CdL(DMF)4](ClO4)2 x EtOH x 0.5H2O (1) adopts a 1D zigzag chain structure,
      [CdL2(ClO4)2] x 3EtOH x H2O (2) and [CdL2(ClO4)(H2O)] (ClO4) x 1.5(o-C6H4Cl2) x
      3EtOH x 6H2O (3) both exhibit 1D polymeric structures that are built from 38
      membered macrocycles. These 1D coordination polymers further pack into chiral
      porous frameworks via pi...pi interactions with a large percentage of void spaces
      that are occupied by solvent molecules and counterions.

PMID- 15732951
TI  - Rational assembly of primitive cubic networks using hexameric stacks of sodium
      aryloxides as nodes.
AB  - The two sodium aryloxide complexes [{(4-R-C6H4ONa)6 x (dioxane)3}infinity], where
      R = Et (1) or F (2), have been prepared and found to form three-dimensional cubic
      networks in the solid state. Each structure is similarly composed of dioxane
      connected Na6O6 aggregates that act as octahedral nodes in directing the assembly
      process. Although the localized metrical parameters within the hexameric cages
      are similar to each other, as well as to those of the molecular analogue [(4-F
      C6H4ONa)6 x (THF)8] (3), the gross architectures show significant variations. In
      particular, the smaller complex 2 ensures effective filling of space through
      transannular Na-F interaggregate interactions, resulting in substantial
      compression of the cubic framework.

PMID- 15732952
TI  - Ferromagnetic ordering of Fe(III) d spins of FeBr4- ions in
      (ethylenedithiotetrathiafulvalenothioquinone-ethylenedithio-1,3-dithiolemethide)
      x FeBr4.
AB  - The 1:1 salt of a new donor molecule, ethylenedithiotetrathiafulvalenothioquinone
      ethylenedithio-1,3-dithiolemethide (1), with FeBr4- ion, 1 x FeBr4, was prepared
      and found to exhibit a room-temperature electrical conductivity of 4 x 10(-2) S
      cm(-1) and semiconducting behavior with an activation energy of 170 meV. The
      paramagnetic susceptibility obeyed the Curie-Weiss law with a Curie constant of
      4.42 emu K mol(-1) and a Weiss temperature of +3.4 K, and below 15 K, this short
      range ferromagnetic interaction increasingly extended to two- and/or three
      dimensional interactions, eventually giving rise to a ferromagnetic ordering,
      whose temperature (TC) was determined to be 1.8 +/- 0.2 K using a resonant
      circuit method. The magnetic field dependence of magnetization showed that the
      saturation of magnetization was accomplished at ca. 60 kOe and the saturated
      value was ca. 5 microB, which is very close to the value obtained only due to
      Fe(III) (S = 5/2) d spins of one FeBr4- ion.

PMID- 15732953
TI  - Dinitrogen partial reduction by formally zero- and divalent vanadium complexes
      supported by the bis-iminopyridine system.
AB  - Reduction of the two trivalent 2,6-{[2,6-(i-Pr)2C6H5]N=C(CH3)}2(C5H3N)VCl3 and
      {[2,6-{[2,6-(i-Pr)2C6H3]N-C=(CH2)}2(C5H3N)]VCl(THF) complexes with excess NaH
      afforded two corresponding end-on dinitrogen-bridged complexes [2,6-{[2,6-(i
      Pr)2C6H5]N=C(CH3)}2(C5H3N)V]2(m-N2).(hexane) (1) and [{[2,6-{[2,6-(i-Pr)2C6H3]N
      C=(CH2)}2(C5H3N)]V]2(m-N2).(hexane) (3). Despite their very close structural
      similarity, the two species have completely different natures. The first is
      paramagnetic and may be regarded as generated by the two-electron attack of two
      formally zerovalent vanadium moieties on the same N2 unit. In the nearly
      diamagnetic 3 instead, the N2 unit has been reduced by two vanadium atoms,
      formally divalent. Structural analysis and DFT calculations have indicated that
      partial reduction of the bridging nitrogen occurred for both complexes while, in
      the case of 1, substantial metal-to-ligand electron transfer also occurs.

PMID- 15732954
TI  - pH-dependent assembly of Keggin-based supramolecular architecture.
AB  - Three Keggin-based supramolecular architectures were synthesized on the basis of
      same molecular building units, showing that the pH value of the reaction plays a
      crucial role in controlling the topological structures of the supramolecular
      architectures.

PMID- 15732955
TI  - Control of iron(III) spin-state in the model complexes of azide hemoprotein by
      porphycene, corrphycene, and hemiporphycene macrocycles.
AB  - Spin states of the iron(III) complexes of porphyrin, porphycene, hemiporphycene,
      and corrphycene bearing both 1-methylimidazole and azide as axial ligands were
      analyzed with infrared (IR) spectroscopy at 20 degrees C. The IR stretching band
      of coordinating azide split into two peaks around 2047 and 2017 cm(-1) reflecting
      an equilibrium between the high- (S = 5/2) and low- (S = 1/2) spin states. The
      high-spin fraction changed over a 0-90% range among the macrocycles,
      demonstrating that the tetrapyrrole array is essential to control the
      equilibrium.

PMID- 15732957
TI  - Reaction of LAlH2 with tert-butyl hydrogenperoxide under C-H Bond activation and
      substitution leads to the formation of a pentacoordinated tert-butylperoxo
      aluminum compound.
AB  - The reaction between beta-diketiminato-stabilized aluminum dihydride LAlH2 and
      tBuOOH leads to the formation of a pentacoordinated tert-butylperoxo aluminum
      compound.

PMID- 15732956
TI  - Unique cooperative binding interaction observed between a minor groove binding Pt
      antitumor agent and Hoechst dye 33258.
AB  - The trinuclear compound [{Pt(NH3)3}2mu-{trans-Pt(NH3)2(H2N(CH2)6NH2)}2(6+)
      (0,0,0/t,t,t) binds to DNA only through noncovalent hydrogen bonding and
      electrostatic interactions. The presence of this 6+ cation allows discrimination
      of binding modes for common DNA ligands: binding of minor-groove agents such as
      Hoechst 33258 is cooperative, and dye-DNA interaction is enhanced whereas
      intercalation as exemplified by ethidium bromide is competitively inhibited.

PMID- 15732958
TI  - Electronic structure and intrinsic redox properties of [2Fe-2S]+ clusters with
      tri- and tetracoordinate iron sites.
AB  - Using potentially bidentate ligands (-SC2H4NH2), we produced [2Fe-2S]+ species of
      different coordination geometries by fission of [4Fe-4S]2+ complexes. Even though
      the ligands are monodentate in the cubane complexes, both mono- and bidentate
      complexes were observed in the [2Fe] fission products through self-assembly
      because of the high reactivity of the tricoordinate iron sites. The electronic
      structure of the [2Fe] species was probed using photoelectron spectroscopy and
      density functional calculations. It was found that tetracoordination
      significantly decreases the electron binding energies of the [2Fe] complexes,
      thus increasing the reducing capability of the [2Fe-2S]+ clusters.

PMID- 15732959
TI  - Novel thiosalamo ligand as a remarkably stable N2S2 salen-type chelate and
      synthesis of a nickel(II) complex.
AB  - Novel N2S2 tetradentate chelate ligand H2tsalamo, which contains both thiol
      groups and C=N moieties, was synthesized as a remarkably stable compound.
      Complexation between H2tsalamo and nickel(II) acetate gave a square planar
      complex [Ni(tsalamo)] as dark brown crystals, whose structure was determined by X
      ray crystallography. In contrast, the corresponding N2O2 ligands, salamo and 3
      MeOsalamo, gave trinuclear and mononuclear complexes, respectively, in which all
      the nickel atoms have octahedral geometry.

PMID- 15732960
TI  - Antiferromagnetic FeIII6 ring and single-molecule magnet MnII3MnIII4 wheel.
AB  - Reactions of a quadridentate ligand [N-(2-hydroxy-5-nitrobenzyl)iminodiethanol]
      with iron and manganese chloride in methanol yielded an antiferromagnetic FeIII6
      ring and a single-molecule magnet MnII3MnIII4 wheel, respectively.

PMID- 15732961
TI  - Luminescent platinum(II) dimers with a cyclometallating aryldiamine ligand.
AB  - Triflate salts of three (Pt(pip2NCN))2(mu-L)2+ (pip2NCNH = 1,3
      bis(piperidylmethyl)benzene) dimers bridged by a series of nitrogen-donor ligands
      (L = pyrazine (pyz), 1,2-bis(4-pyridyl)ethane (bpa), trans-1,2-bis(4
      pyridyl)ethylene (bpe)) are reported. These complexes have been fully
      characterized by 1H NMR spectroscopy and elemental analysis. The X-ray crystal
      structures of [(Pt(pip2NCN))2(mu-pyz)](CF3SO3)2 and [(Pt(pip2NCN))2(mu
      bpe)](CF3SO3)2 x 2CH2Cl2 are reported. [(Pt(pip2NCN))2(mu-pyz)](CF3SO3)2:
      triclinic, P, a = 12.5240(5) A, b = 14.1570(6) A, c = 14.2928(6) A, alpha =
      106.458(1) degrees , beta = 92.527(1) degrees , gamma = 106.880(1) degrees , V =
      2303.46(17) A(3), Z = 2. [(Pt(pip2NCN))2(mu-bpe)](CF3SO3)2 x 2CH2Cl2: monoclinic,
      P21/c, a = 10.1288(6) A, b = 16.3346(9) A, c = 17.4764(10) A, beta = 90.882(2)
      degrees , V = 2891.1(3) A3, Z = 2. These structures and solution measurements
      provide evidence for the strong trans-directing properties of the pip2NCN-
      ligand. The electronic structures of these complexes and those of the 4,4'
      bipyridine (bpy) dimer, (Pt(pip2NCN))2(mu-bpy)2+, also have been investigated by
      UV-visible absorption and emission spectroscopies, as well as cyclic voltammetry.
      The accumulated data indicate that variations in the bridging ligands provide
      remarkable control over the electronic structures and photophysics of these
      complexes. Notably, the bpa dimer exhibits a broad, low-energy emission from a
      metal-centered 3LF excited state, whereas the bpe and bpy dimers exhibit
      structured emission from a lowest pyridyl-centered 3(pi-pi*) excited state. In
      contrast, the pyz dimer exhibits remarkably intense yellow emission tentatively
      assigned to a triplet metal-to-ligand charge-transfer excited state.

PMID- 15732963
TI  - Synthesis and characterization of a porous magnetic diamond framework,
      Co3(HCOO)6, and its N2 sorption characteristic.
AB  - [Co3(HCOO)6](CH3OH)(H2O) (1), the isostructural analogue of the porous magnet of
      coordination framework [Mn3(HCOO)6](CH3OH)(H2O), and its desolvated form
      [Co3(HCOO)6] (2) were prepared and characterized by X-ray and neutron diffraction
      methods, IR, thermal analyses, and BET, and their magnetic properties were
      measured. The parent compound, 1, crystallizes in the monoclinic system, space
      group P21/c, a = 11.254(2) A, b = 9.832(1) A, c = 18.108(3) A, beta = 127.222(2)
      degrees , V = 1595.5(4) A3, Z = 4, R1 = 0.0329 at 180 K. It possesses a unit cell
      volume that is 9% smaller than [Mn3(HCOO)6](CH3OH)(H2O) due to the smaller radius
      of Co2+ ion. Compared with the parent compound 1, the desolvated compound 2 has
      slightly larger lattice with cell parameters of a = 11.2858(4) A, b = 9.8690(4)
      A, c = 18.1797(6) A, beta = 127.193(2) degrees , V = 1613.0(1) A3, R1 = 0.0356 at
      180 K. The cell parameters of 2, obtained from neutron powder data at 2 K, are a
      = 11.309(2) A, b = 9.869(1) A, c = 18.201(3) A, beta = 127.244(8) degrees , V =
      1617.3(5) A3. The pore volume reduces from 33% to 30% by replacing Mn by Co. The
      material exhibits a diamond framework based on Co-centered CoCo4 tetrahedral
      nodes, in which all metal ions have octahedral coordination geometry and all HCOO
      groups link the metal ions in syn-syn/anti modes. It displays thermal stability
      up to 270 degrees C. The compound easily loses guest molecules without loss of
      crystallinity, and it partly reabsorbs water from the atmosphere. Significant N2
      sorption was observed for the desolvated framework suggesting that the material
      possesses permanent porosity. The magnetic properties show a tendency to a 3D
      long-range magnetic ordering, probably antiferromagnetic with a spin canting
      arrangement below 2 K.

PMID- 15732962
TI  - X-ray absorption spectroscopic investigation of the spin-transition character in
      a series of single-site perturbed iron(II) complexes.
AB  - Select ferrous spin-transition complexes with the pentadentate ligand 2,6
      bis(bis(2-pyridyl)methoxymethane)pyridine (PY5) were examined using variable
      temperature solution solid-state magnetic susceptibility, crystallography, X-ray
      absorption spectroscopy (XAS), and UV/vis absorption spectroscopy. Altering the
      single exogeneous ligand, X, of [Fe(PY5)(X)]n)+ is sufficient to change the spin
      state of the complexes. When X is the weak-field ligand Cl-, the resultant Fe
      complex is high-spin from 4 to 300 K, whereas the stronger-field ligand MeCN
      generates a low-spin complex over this temperature range. With intermediate
      strength exogenous ligands (X = N3-, MeOH), the complexes undergo a spin
      transition. [Fe(PY5)(N3)]+, as a crystalline solid, transitions gradually from a
      high-spin to a low-spin complex as the temperature is decreased, as evidenced by
      X-ray crystallography and solid-state magnetic susceptibility measurements. The
      spin-transition is also evident from changes in the pre-edge and EXAFS regions of
      the XAS Fe K-edge spectra on a ground crystalline sample. The spin-transition
      observed with [Fe(PY5)(MeOH)]2+ appears abrupt by solid-state magnetic
      susceptibility measurements, but gradual by XAS analysis, differences attributed
      to sample preparation. This research highlights the strengths of XAS in
      determining the electronic and geometric structure of such spin-transition
      complexes and underscores the importance of identical sample preparation in the
      investigation of these physical properties.

PMID- 15732964
TI  - Dioxygen reactivity of copper and heme-copper complexes possessing an imidazole
      phenol cross-link.
AB  - Recent spectroscopic, kinetics, and structural studies on cytochrome c oxidases
      (CcOs) suggest that the histidine-tyrosine cross-link at the heme a3-CuB
      binuclear active site plays a key role in the reductive O2-cleavage process. In
      this report, we describe dioxygen reactivity of copper and heme/Cu assemblies in
      which the imidazole-phenol moieties are employed as a part of copper ligand LN4OH
      (2-{4-[2-(bis-pyridin-2-ylmethyl-amino)-ethyl]-imidazol-1-yl}-4,6-di -tert-butyl
      phenol). Stopped-flow kinetic studies reveal that low-temperature oxygenation of
      [CuI(LN4OH)]+ (1) leads to rapid formation of a copper-superoxo species
      [CuII(LN4OH)(O2-)]+ (1a), which further reacts with 1 to form the 2:1 Cu:O2
      adduct, peroxo complex [{CuII(LN4OH)}2(O2(2-))]2+ (1b). Complex 1b is also short
      lived, and a dimer Cu(II)-phenolate complex [CuII(LN4O-)]2(2+) (1c) eventually
      forms as a final product in the later stage of the oxygenation reaction. Dioxygen
      reactivities of 1 and its anisole analogue [CuI(LN4OMe)]+ (2) in the presence of
      a heme complex (F8)FeII (3) (F8 = tetrakis(2,6,-difluorotetraphenyl)
      porphyrinate) are also described. Spectroscopic investigations including UV-vis,
      1H and 2H NMR, EPR, and resonance Raman spectroscopies along with
      spectrophotometric titration reveal that low-temperature oxygenation of 1/3 leads
      to formation of a heme-peroxo-copper species [(F8)FeIII-(O2(2-))-CuII(LN4OH)]+
      (4), nu(O-O) = 813 cm(-1). Complex 4 is an S = 2 spin system with strong
      antiferromagnetic coupling between high-spin iron(III) and copper(II) through a
      bridging peroxide ligand. A very similar complex [(F8)FeIII-(O2(2-))
      CuII(LN4OMe)]+ (5) (nu(O-O) = 815 cm(-1)) can be generated by utilizing the
      anisole compound 2, which indicates that the cross-linked phenol moiety in 4 does
      not interact with the bridging peroxo group between heme and copper. This
      investigation thus reveals that a stable heme-peroxo-copper species can be
      generated even in the presence of an imidazole-phenol group (i.e., possible
      electron/proton donor source) in close proximity. Future studies are needed to
      probe key factors that can trigger the reductive O-O cleavage in CcO model
      compounds.

PMID- 15732965
TI  - Structural properties and dissociative fluxional motion of 2,9-dimethyl-1,10
      phenanthroline in platinum(II) complexes.
AB  - A dynamic 1H NMR study has been carried out on the fluxional motion of the
      symmetric chelating ligand 2,9-dimethyl-1,10-phenanthroline (Me2-phen) between
      nonequivalent exchanging sites in a variety of square-planar complexes of the
      type [Pt(Me)(Me2-phen)(PR3)]BArf, 1-14, (BArf = B[3,5-(CF3)2C6H3]4). In these
      compounds, the P-donor ligands PR3 encompass a wide range of steric and
      electronic characteristics [PR3 = P(4-XC6H4)3, X = H 1, F, 2, Cl 3, CF3 4, MeO 5,
      Me 6; PR3 = PMe(C6H5)2 7, PMe2(C6H5) 8, PMe3 9, PEt3 10, P(i-Pr)3 11, PCy(C6H5)2
      12, PCy2(C6H5) 13, PCy3 14]. All complexes have been synthesized and fully
      characterized through elemental analysis, 1H and 31P{1H} NMR. X-ray crystal
      structures are reported for the compounds 8, 11, 14, and for
      [Pt(Me)(phen)(P(C6H5)3)]PF6 (15), all but the last showing loss of planarity and
      a significant rotation of the Me2-phen moiety around the N1-N2 vector. Steric
      congestion brought about by the P-donor ligands is responsible for tetrahedral
      distortion of the coordination plane and significant lengthening of the Pt-N2
      (cis to phosphane) bond distances. Application of standard quantitative analysis
      of ligand effects (QALE) methodology enabled a quantitative separation of steric
      and electronic contributions of P-donor ligands to the values of the platinum
      phosphorus 1J(PtP) coupling constants and of the free activation energies
      DeltaG++ of the fluxional motion of Me2-phen in 1-14. The steric profiles for
      both 1J(PtP) and DeltaG++ show the onset of steric thresholds (at cone angle
      values of 150 degrees and 148 degrees , respectively), that are associated with
      an overload of steric congestion already evidenced by the crystal structures of
      11 and 14. The sharp increase of the fluxional rate of Me2-phen can be assumed as
      a perceptive kinetic tool for revealing ground-state destabilization produced by
      the P-donor ligands. The mechanism involves initial breaking of a metal-nitrogen
      bond, fast interconversion between two 14-electron three-coordinate T-shaped
      intermediates containing eta1-coordinated Me2-phen, and final ring closure. By
      use of the results from QALE regression analysis, a free-energy surface has been
      constructed that represents the way in which any single P-donor ligand can affect
      the energy of the transition state in the absence of aryl or pi-acidity effects.

PMID- 15732966
TI  - Experimental and theoretical studies of carbodiphosphorane-CX2 adducts with
      unusual bonding situations: preparation, crystal structures, and bonding analyses
      of S2CC(PPh3)2, O2CC(PPh3)2, and [(CO)4MS2CC(PPh3)2] (M = Cr, Mo, W).
AB  - We report about the first X-ray structure analyses of the CS2 and CO2 adducts
      with carbodiphosphorane C(PPh3)2 and the synthesis and X-ray structure analysis
      of group 6 carbonyl complexes with compound S2CC(PPh3)2 as a ligand
      [(CO)4MS2CC(PPh3)2] (M = Cr, Mo, W). The nature of the carbon-carbon bonding in
      X2CC(PPh3)2 and in the model compounds X2CC(PH3)2 and the metal-ligand bonding in
      [(CO)4MoS2CC(PH3)2] have been analyzed with charge and energy decomposition
      methods using DFT calculations. Carbodiphosphoranes C(PR3)2 are double electron
      pair donors having sigma- and pi-carbon lone-pair orbitals as the two highest
      occupied MOs.

PMID- 15732967
TI  - Cation-directed synthesis of tungstosilicates. 2. Synthesis, structure, and
      characterization of the open Wells-Dawson anion alpha-[{K(H2O)2}(Si2W18O66)]15-
      and its transiton-metal derivatives [{M(H2O)}(mu-H2O)2K(Si2W18O66)]13- and
      [{M(H2O)}(mu-H2O)2K{M(H2O)4}(Si2W18O66)]11-.
AB  - The dimer alpha-[{K(H2O)2}(Si2W18O66)]15- (1), synthesized by reacting K10A-alpha
      [SiW9O34] with two equivalents of H+ in aqueous solution, has been characterized
      by polarography and 183W NMR spectroscopy. Nine resonance signals have been
      observed with the tetrabutylammonium salt in dimethylformamide/acetonitrile
      solution, in agreement with the crystal structure of the anion which consists of
      two A-alpha-[SiW9O34]10- associated through two W-O-W junctions. This anion
      derives from the Wells-Dawson structure by breaking four W-O-W junctions. The
      pocket between the two-half-anions can be filled by several metal cations.
      Reaction of transition-metal cations with 1 leads to the formation of
      [{M(H2O)}(mu-H2O)2K(Si2W18O66)]13- (1M) (M = Co, Ni, Cu) and [{M(H2O)}(mu
      H2O)2K{M(H2O)4}(Si2W18O66)]11- (1M2) (M = Mn, Co, Ni) complexes. One potassium is
      always included in the pocket with one or two transition metals. Because of the
      shift of the potassium cation to one side of the anion, the coordination modes of
      the two transition metals are different. Crystals of 1, 1M, and 1Co2 potassium
      salts are triclinic (P-1, Z = 2) and crystals of 1M2 potassium salts are
      monoclinic (P2(1)/n, Z = 4). The symmetry of 1Mand 1M2 complexes is C1 and they
      are present in the crystal as racemate inversion pairs.

PMID- 15732968
TI  - Iridium cyclometalated complexes with axial symmetry: time-dependent density
      functional theory investigation of trans-bis-cyclometalated complexes containing
      the tridentate ligand 2,6-diphenylpyridine.
AB  - A new series of iridium cyclometalated complexes with a C/N/C dppy-type ligand
      and a N/N/N tpy-type ligand have been synthesized and characterized by various
      techniques such as mass spectrometry, 1H and 13C NMR, cyclic voltammetry, both
      steady-state and time-resolved emission and absorption studies, and time
      dependent DFT (TDDFT) calculations. The complexes exhibit strong visible
      absorptions and long-lived (1.6-2.0 micros) emissions (lambdamax, ca. 680 nm) in
      room-temperature solution. DFT calculations on the ground-state geometry match
      that of an X-ray crystal structure. TDDFT calculations give accurate predictions
      of the electronic absorption energies and intensities, while geometry
      optimizations on the lowest energy triplet state give accurate energies for the
      emission. Examination of the relevant molecular orbitals shows that the inherent
      asymmetry of the coordination environment offers a unique directional character
      to the emitting excited state, which is predominately LLCT (dppy --> tpy) in
      nature.

PMID- 15732969
TI  - Determination of the g-tensors and their orientations for cis,trans-(L
      N2S2)Mo(V)OX (X = Cl, SCH2Ph) by single-crystal EPR spectroscopy and molecular
      orbital calculations.
AB  - A single-crystal study of cis,trans-(L-N2S2)MoVOCl (1) doped into cis,trans
      (N2S2)MoVIO2 (3) has enabled the g-tensor of 1 and its orientation with respect
      to the molecular structure to be determined. The EPR parameters (g1, 2.004; g2,
      1.960; g3, 1.946; A1, 71.7 x 10(-4) cm(-1); A2, 11.7 x 10(-4) cm(-1); A3, 32.0 x
      10(-4) cm(-1)) of cis,trans-(L-N2S2)MoVOCl [L-N2S2H2 = N,N'-dimethyl-N,N'
      bis(mercaptophenyl)ethylenediamine] mimic those of the low-pH form of sulfite
      oxidase and the "very rapid" species of xanthine oxidase. The principal axis that
      corresponds to g1 is rotated approximately 10 degrees from the Mo[triple bond]O
      vector, while the principal axis that corresponds to g3 is located in the
      equatorial plane and approximately 38 degrees from the Mo-Cl vector. Independent
      theoretical calculations of the g-tensor of 1 were performed using two types of
      techniques: (1) the spectroscopically parametrized intermediate neglect of
      differential overlap technique (INDO/S) combined with single-excitation
      configuration interaction (CIS); (2) a scalar relativistic DFT (BP86 and B3LYP
      functionals) treatment using the zeroth order regular approximation to
      relativistic effects (ZORA) in combination with recently developed accurate
      multicenter mean field spin-orbit operators (RI-SOMF) and the estimation of
      solvent effects using dielectric continuum theory at the conductor-like screening
      model (COSMO) level. The excellent agreement between experiment and theory, as
      well as the high consistency between the INDO/S and BP86/ZORA results, provides a
      sound basis for analysis of the calculated orientation of the g-tensor for
      cis,trans-(L-N2S2)MoVO(SCH2Ph) (2), for which single-crystal EPR data are not
      available but which contains three equatorial sulfur donor atoms, as occurs in
      sulfite oxidase and xanthine oxidase. The implications of these results for the
      EPR spectra of the Mo(V) centers of enzymes are discussed.

PMID- 15732970
TI  - Structural characterization of an enantiopure hydroxo-bridged binuclear iron(III)
      complex with empty one-dimensional helical channels.
AB  - A H-bond capable chiral tetradentate ligand, Fe3+, and acetate ion assembles into
      a hydroxo-bridged binuclear complex with the formula [FeIII2(mu-OH)(mu-OAc)(S
      L)2] x 4H2O (1) where H2S-L = S-2-(2-hydroxy-benzylamino)-3-(1H-imidazol-4-yl)
      propionic acid. The crystal of 1 contains right-handed one-dimensional (1D)
      helical channels with 7.3-9.8 A diameter. A similar reaction with a ligand having
      opposite chirality forms the complex with left-handed helical channels (1a).
      Heating the crystals of 1 at 95 degrees C under reduced pressure selectively
      removes three waters from the channel forming an enantiopure porous crystal with
      empty channels (solvent accessible voids 18% v/v). Intermolecular hydrogen
      bonding between the imidazole N-H and phenolate oxygen in 1-2 forms a C6
      symmetric helix with bridging hydroxo groups pointing inside the channels. All
      the H-bond capable atoms in the ligand along with one water molecule form an
      extended H-bonded network throughout the crystal. Exposing the empty channels of
      2 to iodine vapor indicates partial filling of the channels with iodine. Crystal
      data for 1 x 4H2O include the following: hexagonal, P61, a = b = 13.164(3) A, c =
      36.305 (11) A, alpha = beta = 90 degrees , gamma = 120 degrees , Z = 6, R1 =
      0.0387, wR2 = 0.0842. Crystal data for 1a x 2H2O include the following:
      hexagonal, P6(5), a = b = 13.151(4) A, c = 36.558(2) A, alpha = beta = 90 degrees
      , gamma = 120 degrees , Z = 6, R1 = 0.0416, wR2 = 0.1190. Crystal data for 2 x
      H2O include the following: hexagonal, P61, a = b = 13.160(7) A, c = 36.559 (4) A,
      alpha = beta = 90 degrees , gamma = 120 degrees , Z = 6, R1 = 0.0574, wR2 =
      0.1423.

PMID- 15732971
TI  - Cadmium amido alkoxide and alkoxide precursors for the synthesis of
      nanocrystalline CdE (E = S, Se, Te).
AB  - The synthesis and characterization of a family of alternative precursors for the
      production of CdE nanoparticles (E = S, Se, and Te) is reported. The reaction of
      Cd(NR2)2 where NR2 = N(SiMe3)2 with n HOR led to the isolation of the following:
      n = 1 [Cd(mu-OCH2CMe3)(NR2)(py)]2 (1, py = pyridine), Cd[(mu-OC6H3(Me)(2)
      2,6)2Cd(NR2)(py)]2 (2), [Cd(mu-OC6H3(CHMe2)(2)-2,6)(NR2)(py)]2 (3), [Cd(mu
      OC6H3(CMe3)(2)-2,6)(NR2)(py)]2 (4), [Cd(mu-OC6H2(NH2)(3)-2,4,6)(NR2)(py)]2 (5),
      and n = 2 [Cd(mu-OC6H3(Me)(2)-2,6)(OC6H3(Me)(2)-2,6)(py)2]2 (6), and [Cd(mu
      OC6H3(CMe3)(2)-2,6)(OC6H3(CMe3)(2)-2,6)(THF)]2 (7). For all but 2, the X-ray
      crystal structures were solved as discrete dinuclear units bridged by alkoxide
      ligands and either terminal -NR2 or -OR ligands depending on the stoichiometry of
      the initial reaction. For 2, a trinuclear species was isolated using four mu-OR
      and two terminal -NR2 ligands. The coordination of the Cd metal center varied
      from 3 to 5 where the higher coordination numbers were achieved by binding Lewis
      basic solvents for the less sterically demanding ligands. These complexes were
      further characterized in solution by 1H, 13C, and 113Cd NMR along with solid
      state 113Cd NMR spectroscopy. The utility of these complexes as "alternative
      precursors" for the controlled preparation of nanocrystalline CdS, CdSe, and CdTe
      was explored. To synthesize CdE nanocrystals, select species from this family of
      compounds were individually heated in a coordinating solvent (trioctylphosphine
      oxide) and then injected with the appropriate chalcogenide stock solution.
      Transmission electron spectroscopy and UV-vis spectroscopy were used to
      characterize the resultant particles.

PMID- 15732972
TI  - Redox control of light-induced charge separation in a transition metal cluster:
      photochemistry of a methyl viologen-substituted [Os3(CO)10(alpha-diimine)]
      cluster.
AB  - (Sub)picosecond transient absorption (TA) and time-resolved infrared (TRIR)
      spectra of the cluster [Os3(CO)10-(AcPy-MV)]2+ (the dication AcPy-MV = AcPy-MV2+
      = [2-pyridylacetimine-N-(2-(1'-methyl-4,4'-bipyridine-1,1'-diium-1
      yl)ethyl)](PF6)2) (1(2+)) reveal that photoinduced electron transfer to the
      electron-accepting 4,4'-bipyridine-1,1'-diium (MV2+) moiety competes with the
      fast relaxation of the initially populated sigmapi excited state of the cluster
      to the ground state and/or cleavage of an Os-Os bond. The TA spectra of cluster
      1(2+) in acetone, obtained by irradiation into its lowest-energy absorption band,
      show the characteristic absorptions of the one-electron-reduced MV*+ unit at 400
      and 615 nm, in accordance with population of a charge-separated (CS) state in
      which a cluster-core electron has been transferred to the lowest pi orbital of
      the remote MV2+ unit. This assignment is confirmed by picosecond TRIR spectra
      that show a large shift of the pilot highest-frequency nu(CO) band of 1(2+) by
      ca. +40 cm(-1), reflecting the photooxidation of the cluster core. The CS state
      is populated via fast (4.2 x 10(11) s(-1)) and efficient (88%) oxidative
      quenching of the optically populated sigmapi excited state and decays
      biexponentially with lifetimes of 38 and 166 ps (1.2:1 ratio) with a complete
      regeneration of the parent cluster. About 12% of the cluster molecules in the
      sigmapi excited state form long-lived open-core biradicals. In strongly
      coordinating acetonitrile, however, the cluster core-to-MV2+ electron transfer in
      cluster 1(2+) results in the irreversible formation of secondary photoproducts
      with a photooxidized cluster core. The photochemical behavior of the
      [Os3(CO)10(alpha-diimine-MV)]2+ (donor-acceptor) dyad can be controlled by an
      externally applied electronic bias. Electrochemical one-electron reduction of the
      MV2+ moiety prior to the irradiation reduces its electron-accepting character to
      such an extent that the photoinduced electron transfer to MV(*+) is no longer
      feasible. Instead, the irradiation of reduced cluster 1(*+) results in the
      reversible formation of an open-core zwitterion, the ultimate photoproduct also
      observed upon irradiation of related nonsubstituted clusters [Os3(CO)10(alpha
      diimine)] in strongly coordinating solvents such as acetonitrile.

PMID- 15732973
TI  - Blue luminescent 2-(2'-pyridyl)benzimidazole derivative ligands and their orange
      luminescent mononuclear and polynuclear organoplatinum(II) complexes.
AB  - Five new 2-(2'-pyridyl)benzimidazole derivative ligands, 1,4-bis[2-(2'
      pyridyl)benzimidazolyl]benzene (1,4-bmb), 4,4'-bis[2-(2'
      pyridyl)benzimidazolyl]biphenyl (bmbp), 1-bromo-4-[2-(2'
      pyridyl)benzimidazolyl]benzene (Brmb), 1,3-bis[2-(2'
      pyridyl)benzimidazolyl]benzene (1,3-bmb), and 1,3,5-tris[2-(2'
      pyridyl)benzimidazolyl]benzene (tmb), have been synthesized by Ullmann
      condensation methods. The corresponding mononuclear and polynuclear PtII
      complexes, Pt2(1,4-bmb)Ph4 (1), Pt2(bmbp)Ph4 (2), Pt(Brmb)Ph2 (3), Pt2(1,3
      bmb)Ph4 (4), and Pt3(tmb)Ph6 (5), have been obtained by the reaction of the
      appropriate ligand with [PtPh2(SMe2)]n. The structures of the free ligands 1,4
      bmb, bmbp, and tmb, as well as the complexes 1-3, were determined by single
      crystal X-ray diffraction. All ligands display fluorescent emissions in the
      purple/blue region of the spectrum at ambient temperature and phosphorescent
      emissions in the blue/green region at 77 K, which are attributable to ligand
      centered pi --> pi* transition. No ligand-based emission was observed for the
      PtII complexes 1-5. All PtII complexes display orange/red emissions at 77 K in a
      frozen solution or in the solid state, attributable to metal-to-ligand charge
      transfers (MLCT). Variable-temperature 1H NMR experiments establish that
      complexes 1, 4, and 5 exist in isomeric forms in solution at ambient temperature
      due to the hindered rotation of the square PtC2N2 planes in the complexes.

PMID- 15732974
TI  - Iridium(III) complexes with orthometalated quinoxaline ligands: subtle tuning of
      emission to the saturated red color.
AB  - Rational design and syntheses of four iridium complexes (1-4) bearing two
      substituted quinoxalines and an additional 5-(2-pyridyl) pyrazolate or triazolate
      as the third coordinating ligand are reported. Single-crystal X-ray diffraction
      studies of 1 reveal a distorted octahedral geometry, in which two dpqx ligands
      adopt an eclipse configuration, for which the quinoxaline N atoms and the C atoms
      of orthometalated phenyl groups are located at the mutual trans- and cis
      positions, respectively. The lowest absorption band for all complexes consists of
      a mixture of heavy-atom Ir(III)-enhanced 3MLCT and 3pipi* transitions, and the
      phosphorescent peak wavelength can be fine-tuned to cover the spectral range of
      622-649 nm with high quantum efficiencies. The cyclic voltammetry was measured,
      showing a reversible, metal-centered oxidation with potentials at 0.76-1.03 V, as
      well as two reversible reduction waves with potentials ranging from -1.61 to 
      2.06 V, attributed to the sequential addition of two electrons to the more
      electron-accepting heterocyclic portion of two distinctive cyclometalated C/N
      ligands. Complex 1 was used as the representative example to fabricate the red
      emitting PLEDs by blending it into a PVK-PBD polymer mixture. The devices
      exhibited the characteristic emission profile of 1 with peak maxima located at
      640 nm. The maximum external quantum efficiency was 3.15% ph/el with a brightness
      of 1751 cd/m2 at a current density of 67.4 mA/cm2, and the maximum brightness of
      7750 cd/m2 was achieved at the applied voltage of 21 V and with CIE coordinates
      of (0.64, 0.31).

PMID- 15732975
TI  - A new bimetallic intercalated 3-D assembly magnet [{(323)Ni}3{FeIII(CN)6}2]n x
      12nH2O (323 = N,N'-bis(3-aminopropyl) ethylenediamine): an unprecedented
      concomitant presence of meridional and facial arrangment of ferricyanide anion.
AB  - A novel molecular based magnet of three-dimensional (3-D) cyanide-bridged
      bimetallic assembly, [{(323)Ni}3{FeIII(CN)6}2]n x 2nH2O where 323 = N,N'-bis(3
      aminopropyl) ethylenediamine, was synthesized and structurally characterized. The
      compound crystallizes in the orthorhombic space group Pbca with a = 15.6560 A, b
      = 15.2910 A, c = 50.9120 A, and Z = 8. The assembly has two intercalated 3-D
      networks created by FeIII-CN-NiII-NC-FeIII linkages. The ferricyanide anion
      adopts both facial and meridional arrangements through the linkage. Interesting
      magnetic properties including 3-dimensional magnetic ordering were revealed. The
      assembly displays 3-dimensional magnetic ordering below 5.2 +/- 0.1 K and field
      induced magnetic behavior below 5.1 +/- 0.1 K and above 1.15 +/-0.05 kOe.

PMID- 15732976
TI  - Generation of a plastic crystal including methane rotator within metal-organic
      cavity by forcible gas adsorption.
AB  - The structural determination of saturated adsorbed methane inside a metal-organic
      cavity by the forcible pressure swing adsorption method (ca. 13 MPa) through a
      gas-adsorption equilibrium state gives a methane inclusion crystal even at 298 K.
      The adsorbed methane molecules regularly locate in the pocket-like narrow corners
      of the necks of the 1-D channel without disorder. The thermal motion of the
      pseudo-spherical methane molecules seems to be effectively suppressed in its
      translation mode but allowed rotation. In cooling to 90 K, the crystal structure
      remained essentially unchanged while the thermal motion decreased, indicating
      that a lower temperature reduces the rotation of the adsorbed pseudo-spherical
      methane. The observed crystal structure could also be influenced by a reduction
      of the vibrational magnitude, and a phase transition from a static disordered
      structure to an ordered state might occur. The observed crystal state at a higher
      temperature should have a plastic crystal nature in terms of the randomness of
      the orientation of incorporated guests. The single-crystal adsorbent is effective
      for crystallographic observation of the thermal activated guest forced into
      regular alignment in the crystal lattice, which can be used as a model of the
      supercritical fluid.

PMID- 15732977
TI  - Fe-N-O structure and bonding in six-coordinate {FeNO}6 porphyrinates containing
      imidazole: implications for reactivity of coordinated NO.
AB  - We report density functional theory calculations on six-coordinate ferric-NO
      ({FeNO}6) porphyrinates that contain either imidazole or imidazolate as the trans
      axial ligand. Our results show that the sensitivities of the Fe-NO and N-O
      stretching frequencies to cis and trans influences are directly correlated. In
      other words, as one decreases so does the other for both the imidazole and the
      imidazolate complexes. This correlation is opposite that of the isoelectronic
      ferrous-CO systems, whose Fe-CO and C-O frequencies are well-known to be
      inversely correlated. Based on the results of our calculations, the molecular
      origin of the direct correlation in {FeNO}6 porphyrinates can be explained by
      trends in the electron density distributions within the HOMO or HOMO-1, which
      exhibits Fe-NO and N-O pi-antibonding character. Variability in the Fe-N-O pi
      antibonding character of the HOMO or the HOMO-1 modulates the angleFeNO as well
      as the Fe-NO and N-O bond strengths in concert. Orbital interactions in the six
      coordinate FeIIINO porphyrin complexes are compared and contrasted with those of
      the isoelectronic FeIICO analogues, and an overall view of {FeNO}6 bonding in
      these complexes is set forth.

PMID- 15732978
TI  - Atomic silicon in siloxanic networks: the nature of the oxo-oxygen-silicon bond.
AB  - The existence of atomic silicon cryptates in siloxanic networks has been studied
      theoretically via density functional calculations. By modeling with model
      molecules the candidate sites to host atomic silicon, we found that metastable
      adducts can be formed only in regions where the siloxanic network is not
      subjected to steric constraints; stationary states are instead unstable in highly
      reticulated siloxanic networks. The nature of the oxo-oxygen-silicon bond at the
      SiO2 surface is analyzed in detail. It is concluded that silicon is kept at the
      surface in atomic-like configuration by (i) sigma charge donation from oxo-oxygen
      atoms into the empty silicon psigma orbital; (ii) pi charge back-donation from
      singly occupied silicon 3ppi orbitals into empty sigma* model molecule orbitals.
      Surprisingly, these results attribute to atomic silicon the character of
      bifunctional Lewis acid.

PMID- 15732979
TI  - Synthesis and structure of Pt(II) phosphonato-phosphine complexes and of a P,O
      stabilized metal-metal-bonded Pt2Ag2 complex.
AB  - As part of our interest in the design and reactivity of P,O ligands, and because
      the insertion chemistry of small molecules into a metal alkyl bond is very
      dependent on the ancillary ligands, the behavior of Pt-methyl complexes
      containing the beta-phosphonato-phosphine ligand rac-Ph2PCH(Ph)P(O)(OEt)2
      (abbreviated PPO in the following) toward CO insertion has been explored. New,
      mononuclear Pt(II) complexes containing one or two PPO ligands, [PtClMe(kappa2
      PPO)] (1), [Pt{C(O)Me}Cl(kappa2-PPO)] (2), [PtMe(CO)(kappa2-PPO)]OTf (3 x OTf),
      [PtMe(OTf)(kappa2-PPO)] (4), trans-[PtClMe(kappa1-PPO)2] (5), [PtMe(kappa2
      PPO)(kappa1-PPO)]BF4 (6 x BF4), [PtMe(kappa2-PPO)(kappa1-PPO)]OTf (6 x OTf), and
      [Pt{C(O)Me}(kappa2-PPO)(kappa1-PPO)]BF4 (7 x BF4) have been prepared and
      characterized. Hemilability of the ligands is observed in the cations 6 and 7 in
      which the terminally bound and chelating PPO ligands exchange their role on the
      NMR time-scale. The acetyl complexes 2 and 7 are stable in solution, but the
      former deinserts CO upon chloride abstraction. We also demonstrate the ability of
      PPO to behave as an assembling ligand and to stabilize a heterometallic Pt-Ag
      metal complex, [PtMe(kappa2-PPO){mu-(eta1-P;eta1-O)PPO)}Ag(OTf)(Pt-Ag)]OTf (8 x
      OTf), which was obtained by reaction of 5 with AgOTf to generate more reactive,
      cationic complexes. Whereas the first equivalent of AgOTf abstracted the chloride
      ligand, the second equivalent added to the cationic complex with formation of a
      Pt-Ag bond (2.819(1) A). The complexes 1, 2, 4, 5 x CH2Cl2, and (8 x OTf)2 have
      been structurally characterized by single-crystal X-ray diffraction. The latter
      has a dimeric nature in the solid state, with two silver-bound triflates acting
      as bridging ligands between two Pt-Ag moieties. In addition to the Ag-Pt bond,
      the Ag+ cation is stabilized by a dative O -->Ag interaction involving one of the
      PPO ligands.

PMID- 15732980
TI  - Thermodynamic study of the complexation of trivalent actinide and lanthanide
      cations by ADPTZ, a tridentate N-donor ligand.
AB  - To better understand the bonding in complexes of f-elements by polydentate N
      donor ligands, the complexation of americium(III) and lanthanide(III) cations by
      2-amino-4,6-di-(pyridin-2-yl)-1,3,5-triazine (ADPTZ) was studied using a
      thermodynamic approach. The stability constants of the 1:1 complexes in a
      methanol/water mixture (75/25 vol %) were determined by UV-visible
      spectrophotometry for every lanthanide(III) ion (except promethium), and
      yttrium(III) and americium(III) cations. The thermodynamic parameters (DeltaH
      degrees , DeltaS degrees) of complexation were determined from the temperature
      dependence of the stability constants and by microcalorimetry. The trends of the
      variations of DeltaG degrees , DeltaH degrees , and DeltaS degrees across the
      lanthanide series are compared with published results for other tridentate
      ligands and confirm strongly ionic bonding in the lanthanide-ADPTZ complexes.
      Comparison of the thermodynamic properties between the Am- and Ln-ADPTZ complexes
      highlights an increase in stability of the complexes by a factor of 20 in favor
      of the americium cation. This difference arises from a more exothermic reaction
      enthalpy in the case of Am, which is correlated with a greater degree of
      covalency in the americium-nitrogen bonds. Quantum chemistry calculations
      performed on a series of trivalent actinide and lanthanide-ADPTZ complexes
      support the experimental results, showing a slightly greater covalence in the
      actinide-ligand bonds that originates from a charge transfer from the ligand
      sigma orbitals to the 5f and 6d orbitals of the actinide ion.

PMID- 15732981
TI  - High-nuclearity iridium carbonyl clusters containing phenylgermyl ligands:
      synthesis, structures, and reactivity.
AB  - The reaction of Ir4(CO)12 with Ph3GeH at 97 degrees C has yielded the new
      tetrairidium cluster complexes Ir4(CO)7(GePh3)(mu-GePh2)2[mu3-eta3-GePh(C6H4)](mu
      H)2 (10) and Ir4(CO)8(GePh3)2(mu-GePh2)4 (11). The structure of 10 consists of a
      tetrahedral Ir4 cluster with seven terminal CO groups, two bridging GePh2)
      ligands, an ortho-metallated bridging mu3-eta3-GePh(C6H4) group, a terminal GePh3
      ligand, and two bridging hydrido ligands. Compound 11 consists of a planar
      butterfly arrangement of four iridium atoms with four bridging GePh2 and two
      terminal GePh3 ligands. The same reaction at 125 degrees C yielded the two new
      triiridium clusters Ir3(CO)5(GePh3)(mu-GePh2)3(mu3-GePh)(mu-H) (12) and
      Ir3(CO)6(GePh3)3(mu-GePh2)3 (13). Compound 12 contains a triangular Ir3 cluster
      with three bridging GePh2), one triply bridging GePh, and one terminal GePh3
      ligand. The compound also contains a hydrido ligand that bridges one of the Ir-Ge
      bonds. Compound 13 contains a triangular Ir3 cluster with three bridging GePh2
      and three terminal GePh3 ligands. At 151 degrees C, an additional complex,
      Ir4H4(CO)4(mu-GePh2)4(mu4-GePh)2 (14), was isolated. Compound 14 consists of an
      Ir4 square with four bridging GePh2, two quadruply bridging GePh groups, and four
      terminal hydrido ligands. Compound 12 reacts with CO at 125 degrees C to give the
      compound Ir3(CO)6(mu-GePh2)3(mu3-GePh) (15). Compound 15 is formed via the loss
      of the hydrido ligand and the terminal GePh3 ligand and the addition of one
      carbonyl ligand to 12. All compounds were fully characterized by IR, NMR, single
      crystal X-ray diffraction analysis, and elemental analysis.

PMID- 15732982
TI  - Selective generation of organic aggregates included within metal-organic
      micropores through vapor adsorption.
AB  - The ethanol vapor adsorption behavior and the inclusion crystal structure of a 1D
      transformable coordination polymer host were characterized. The adsorption jump
      was observed during phase transition or two-phase equilibrium with abnormal
      adsorption enthalpy caused by the nature of "mass induced phase transition." The
      included ethanol guests selectively form O-H...O hydrogen bonded pairs inside
      channels, suggesting selective construction of a specific cluster/aggregate in
      pores under control of thermodynamic factors and cooperative intermolecular
      interactions among the guest and channel surface.

PMID- 15732984
TI  - Aluminum salen complexes and tetrabutylammonium salts: a binary catalytic system
      for production of polycarbonates from CO2 and cyclohexene oxide.
AB  - A series of complexes of the form (salen)AlZ, where H2salen = N,N'
      bis(salicylidene)-1,2-phenylenediimine and various other salen derivatives and Z
      = Et or Cl, have been synthesized. Several of these complexes have been
      characterized by X-ray crystallography. An investigation of the utilization of
      these aluminum derivatives along with both ionic and neutral bases as cocatalysts
      for the copolymerization of carbon dioxide and cyclohexene oxide has been
      conducted. By studying the reactivity of these complexes for this process as
      substituents on the diimine backbone and phenolate rings are altered, we have
      observed that aluminum prefers electron-withdrawing groups on the salen ligands,
      thereby producing an electrophilic metal center to be most active toward
      production of polycarbonates from CO2 and cyclohexene oxide. For example, the
      complex derived from H2salen = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2
      ethylenediimine is essentially inactive when compared to the analogous derivative
      containing nitro substituents in the 3-positions of the phenolate groups. This is
      to be contrasted with the catalytic activity observed for the (salen)CrX systems,
      where electron-donating salen ligands greatly enhanced the reactivity of these
      complexes for the coupling of CO2 and epoxides. While (salen)AlZ complexes are
      capable of producing poly(cyclohexene oxide) carbonate with low amounts of
      polyether linkage along with small quantities of cyclic carbonate byproducts,
      their reactivities, covering a turnover frequency range of 5.2-35.4 mol of
      epoxide consumed/(mol of Al x h), are greatly reduced when compared to their
      (salen)CrX analogues under identical reaction conditions.

PMID- 15732983
TI  - (salen)MnIII compounds as nonpeptidyl mimics of catalase. Mechanism-based tuning
      of catalase activity: a theoretical study.
AB  - We present the results of the first theoretical investigation of salen-manganese
      complexes as synthetic catalytic scavengers of hydrogen peroxide molecules that
      mimic catalase enzymes. Catalase mimics can be used as therapeutic agents against
      oxidative stress in treatment of many diseases, including Alzheimer's disease,
      stroke, heart disease, aging, and cancer. A ping-pong mechanism approach has been
      considered to describe the H2O2 dismutation reaction. The real compounds reacting
      with a peroxide molecule were utilized in our BP density functional calculations
      to avoid uncertainties connected with using incomplete models. Part I of the
      dismutation reaction-converting a peroxide molecule into a water molecule with
      simultaneous oxidation of the metal atom of the catalyst-can be done quite
      effectively at the Mn catalytic center. To act as catalytic scavengers of
      hydrogen peroxide, the oxomanganese salen complexes have to be deoxidized during
      part II of the dismutation reaction. It has been shown that there are two
      possible reaction routes for the second part of the dismutation reaction: the top
      and the side substrate approach routes. Our results suggest that the catalyst
      could be at least temporarily deactivated (poisoned) in the side approach
      reaction route due to the formation of a kinetically stable intermediate.
      Overall, the side approach reaction route for the catalyst recovery is the
      bottleneck for the whole dismutation process. On the basis of the detailed
      knowledge of the mode of action of the (salen)MnIII catalase mimics, we suggest
      and rationalize structural changes of the catalyst that should lead to better
      therapeutic properties. The available experimental data support our conclusions.
      Our findings on the reaction dismutation mechanism could be the starting point
      for further improvement of salen-manganese complexes as synthetic catalytic
      scavengers of reactive oxygen species.

PMID- 15732985
TI  - Hydrothermal single-crystal growth in the systems Ag/Hg/X/O (X = VV, AsV):
      crystal structures of (Ag3Hg)VO4, (Ag2Hg2)3(VO4)4, and (Ag2Hg2)2(HgO2)(AsO4)2
      with the unusual tetrahedral cluster cations (Ag3Hg)3+ and (Ag2Hg2)4+ and crystal
      structure of AgHgVO4.
AB  - Single crystals of (Ag3Hg)VO4 (I), (Ag2Hg2)3(VO4)4 (II), AgHgVO4 (III), and
      (Ag2Hg2)2(HgO2)(AsO4)2 (IV) were grown under hydrothermal conditions (250 degrees
      C, 5 d) from starting mixtures of elementary mercury, silver nitrate, ammonium
      vanadate, and disodium hydrogenarsenate, respectively. All crystal structures
      were determined from X-ray diffraction data, and their chemical compositions were
      confirmed by electron microprobe analysis. I crystallizes in the tillmannsite
      structure, whereas II-IV adopt new structure types: (I) I4, Z = 2, a = 7.7095(2)
      A, c = 4.6714(2) A, 730 structure factors, 24 parameters, R[F2 > 2sigma(F2)] =
      0.0365; (II) I42d, Z = 4, a = 12.6295(13) A, c = 12.566(3) A, 1524 structure
      factors, 55 parameters, R[F2 > 2sigma(F2)] = 0.0508; (III) C2, Z = 4, a =
      9.9407(18) A, b = 5.5730(8) A, c = 7.1210(19) A, beta = 94.561(10) degrees , 1129
      structure factors, 48 parameters, R[F2 > 2sigma(F2)] = 0.0358; (IV) P31c, Z = 2,
      a = 6.0261(9) A, c = 21.577(4) A, 1362 structure factors, 52 parameters, R[F2 >
      2sigma(F2)] = 0.0477. The most striking structural features of I, II, and IV are
      the formation of tetrahedral cluster cations (Ag3Hg)3+ and (Ag2Hg2)4+,
      respectively, built of statistically distributed Ag and Hg atoms with a metal
      metal distance of about 2.72 A. The electronic structure of these clusters can
      formally be considered as two-electron-four-center bonding. The crystal structure
      of III differs from the protrusive structure types insofar as silver and mercury
      are located on distinct crystallographic sites without a notable metal-metal
      interaction >3.55 A. All crystal structures are completed by tetrahedral oxo
      anions XO4(3-) (X = VV, AsV) and for IV additionally by a mercurate group, HgO2(2
      ).

PMID- 15732986
TI  - Metal complexes of meso-amino-octaethylporphyrin and the oxidation of NiII(meso
      amino-octaethylporphyrin).
AB  - The crystal structures of meso-NH2-OEPH2, NiII(meso-NH2-OEP), and CuII(meso-NH2
      OEP) (where OEP is the dianion of meso-amino-octaethylporphyrin) have been
      determined to examine the effects of the meso-substituent on the geometry of the
      ligand. CuII(meso-NH2-OEP) has a nearly planar geometry while the free ligand
      itself and NiII(meso-NH2-OEP) have ruf conformations. NiII(meso-NH2-OEP) is much
      less reactive toward oxidation than are (py)2FeII(meso-NH2-OEP), ClFeIII(meso-NH2
      OEP), or NiII(meso-HO-OEP), which all undergo oxidation in pyridine solution when
      exposed to dioxygen. Treatment of NiII(meso-NH2-OEP) with iron(III) chloride in
      chloroform solution does result in oxidation of the ligand in two separate
      processes. One involves oxygenation at the trans-meso position, while the other
      results in ring cleavage and removal of the amino function. The open-chain
      tetrapyrrole complex, NiII(OEB-CO2Et), has been characterized by single-crystal X
      ray diffraction and shown to contain a helical ligand with a four-coordinate
      nickel ion.

PMID- 15732987
TI  - High-pressure synthesis and transport properties of a new binary germanide, SrGe6
      delta (delta congruent with 0.5), with a cagelike structure.
AB  - A new germanide, SrGe6-delta (delta congruent with 0.5), was synthesized by the
      reaction of Sr and Ge mixtures under a pressure of 5 GPa at 1200 degrees C. It
      crystallized in the orthorhombic space group Cmcm (No. 63) with a = 4.0981(6) A,
      b = 11.159(1) A, c = 12.6825(8) A, V = 580.0(1) A3, and Z = 4. SrGe6-delta is
      composed of a Ge covalent network having a cagelike structure and Sr atoms
      situated in the cages. Each Ge atom is coordinated by four neighboring Ge atoms.
      The coordination polyhedra are fairly distorted from an ideal tetrahedron, and
      the Ge network contains vacancies and disordering. The resistivity shows metallic
      behavior down to 2 K, and the positive thermoelectric power indicates the
      dominant carriers to be holes.

PMID- 15732988
TI  - A theoretical study on the mechanism of the reductive half-reaction of xanthine
      oxidase.
AB  - On the basis of the crystal structure of an aldehyde oxidoreductase, Huber et al.
      proposed a catalytic mechanism for the reductive half-reaction of xanthine
      oxidase which involves nucleophilic addition of Mo-bound hydroxide (Moco 1) to
      the substrate and hydride transfer from the substrate to sulfido group (Mo=S).
      Density functional theory calculations have been carried out for the oxidation of
      formaldehyde, acetaldehyde, formamide, and formamidine with Moco 2 to understand
      more detailed catalytic pathways. Our calculation results indicate that the
      anionic catalyst model acts as a nucleophile and is reactive for the oxidation of
      aldehyde substrates, which are reactive for nucleophilic addition. In these
      cases, a concerted mechanism is found to be more favorable than a stepwise
      mechanism. The concerted mechanism is further shown to be promoted by the
      presence of a nearby water molecule, in the active site, which serves as a Lewis
      acid for the nucleophilic addition of hydroxide. For less reactive formamide and
      formamidine (a model for xanthine) substrates, the calculated activation energies
      with the above mechanisms are high. These reactions also do not benefit from the
      presence of the water molecule. The results indicate that different catalyst
      forms might be responsible for the oxidation of different substrates, which could
      be regulated by the enzyme active site environment.

PMID- 15732989
TI  - Structure, spectroscopic properties, and reversible solid-to-solid reactions of
      metal complexes of 5-nitro-pyrimidin-2-olate.
AB  - In searching for coordination polymers containing the highly polarized 5-nitro
      pyrimidin-2-olate ligand (NP), a number of species containing 3d transition
      metals have been prepared and characterized, namely Co(NP)2(H2O)4, [Co(NP)2]n,
      Ni(NP)2(H2O)4, [Ni(NP)2]x, and [Zn(NP)2]n. Their structures have been determined
      by X-ray powder diffraction methods. The hydrated compounds contain mononuclear
      M(NP)2(H2O)4 units interconnected by means of a three-dimensional (3D) network of
      hydrogen bonds. The homoleptic species, at variance from the already known
      metal(II) pyrimidin-2-olate ones, crystallize as two-dimensional (2D) slabs,
      where the metal coordination is of the MN3O kind. The electron-withdrawing nitro
      group, never bound to the metal ion, is likely to influence the observed
      stereochemistry through steric and dipolar effects within the crystal lattice.
      The thermal, spectroscopic, and magnetic properties of these species are
      presented. The M(NP)2(H2O)4/[M(NP)2]x,n systems interconvert reversibly upon
      dehydration/rehydration processes.

PMID- 15732990
TI  - Interactions of Rh(III)-dihydrido-bis(phosphine) complexes with semicarbazones.
AB  - Interaction of cis,trans,cis-[Rh(H)2(PR3)2(acetone)2]PF6 complexes (R = aryl or
      R3 = Ph2Me, Ph2Et) under H2 with E-semicarbazones gives the Rh(III)-dihydrido
      bis(phosphine)-semicarbazone species cis,trans-[Rh(H)2(PR3)2{R'(R' ')C=N
      N(H)CONH2}]PF6, where R' and R' ' are Ph, Et, or Me. The complexes are generally
      characterized by elemental analysis, 31P{1H} NMR, 1H NMR, and IR spectroscopies,
      and MS. X-ray analysis of three PPh3 complexes reveals chelation of E
      semicarbazones by the imine-N atom and the carbonyl-O atom. In contrast, the
      corresponding reaction of [Rh(H)2(PPhMe2)2(acetone)2]PF6 with acetophenone
      semicarbazone gives the ortho-metalated-semicarbazone species cis-[RhH(PPhMe2)2{o
      C6H4(Me)C=N-N(H)CONH2}]PF6. The X-ray structure of E-propiophenone semicarbazone
      is also reported. Rhodium-catalyzed, homogeneous hydrogenation of semicarbazones
      was not observed even at 40 atm H2.

PMID- 15732991
TI  - Functionalized platinum(II) terpyridyl alkynyl complexes as colorimetric and
      luminescence pH sensors.
AB  - A series of platinum(II) terpyridyl alkynyl complexes that have been derivatized
      with basic amino functionalities, [Pt(tpy)(C[triple bond]C-C6H4-NR2-4]X (X = OTf
      , R = CH3 1, R = CH2CH2OCH3 2, R = H 3; X = Cl-, R = CH3 4, R = CH2CH2OCH3 5, R =
      H 6) (tpy = 2,2':6',2' '-terpyridine), have been synthesized and characterized.
      Their photophysical responses at various acid concentrations were studied. The
      abilities of the complexes to function as colorimetric and luminescence pH
      sensors were demonstrated with dramatic color changes and luminescence
      enhancement upon introduction of acid.

PMID- 15732992
TI  - First example of low-valence ion substitution in Ln5O(OPri)13: mixed-valence
      europium oxoalkoxide [EuIII4EuIIO(OPri)12(HOPri)]HOPri.
AB  - The novel mixed-valence alkoxide [Eu3+(4)Eu2+O(OPri)12(HOPri)]HOPri (1) has been
      prepared and structurally and spectroscopically characterized. The three
      synthesis routes (i) metathesis of 4EuCl3, EuI2, and 14KOPri combined with
      hydrolysis with 1H2O, (ii) oxidation of 5[Eu4(OPri)10(HOPri)3]2HOPri with 1.5O2,
      and (iii) reduction of Eu5O(OPri)13 with 0.8[Eu4(OPri)10(HOPri)3]2HOPri all
      yielded pure 1, whereas (iv) reduction of Eu5O(OPri)13 with 0.36-0.5 mol of
      europium metal produced impure 1. The compound, having the average Eu oxidation
      number +2.8, is very sensitive toward further oxidation to Eu5O(OPri)13 and is
      part of a redox series of europium 2-propoxides with average oxidation states
      +2.5, +2.8, and +3. The square pyramidal molecular structure, containing an oxo
      oxygen atom in the basal plane, is similar to that of the well-known
      Ln5O(OPri)13; the main difference is the substitution of an Eu3+(-)OPri pair for
      an Eu2+(-)HOPri pair in the basal plane. Fourier transform infrared (FT-IR) and
      UV-visible spectroscopy showed that the solid-state structure was retained on
      dissolution in hexane and toluene-HOPri. The compound was further characterized
      by differential scanning calorimetry and solubility studies.

PMID- 15732993
TI  - Deprotonation reactions of zirconium and hafnium amide complexes H2N
      M[N(SiMe3)2]3 and subsequent silyl migration from amide -N(SiMe3)2 to imide =NH
      ligands.
AB  - Ammonolysis of previously reported Cl-M[N(SiMe3)2]3 (M = Zr, 1a; Hf, 1b) leads to
      the formation of peramides H2N-M[N(SiMe3)2]3 (M = Zr, 2a; Hf, 2b) which upon
      deprotonation by LiN(SiMe3)2 or Li(THF)3SiPh2But yields imides Li+(THF)n{HN(-)
      M[N(SiMe3)2]3} (M = Zr, 3a; Hf, 3b). One -SiMe3 group in 3a-b undergoes silyl
      migration from a -N(SiMe3)2 ligand to the imide =NH ligand to give
      Li+(THF)2{Me3SiN(-)-M[NH(SiMe3)][N(SiMe3)2]2} (M = Zr, 4a; Hf, 4b) containing an
      imide =N(SiMe3) ligand. The kinetics of the 3a --> 4a conversion was investigated
      between 290 and 315 K and was first-order with respect to 3a. The activation
      parameters for this silyl migration are DeltaH++ = 13.3(1.3) kcal/mol and
      DeltaS++ = -34(3) eu in solutions of 3a (in toluene-d8 with 1.07 M THF) prepared
      in situ. THF in the mixed solvent promoted the 3a --> 4a reaction. The effect of
      THF on the rate constants of the conversion has been studied, and the kinetics of
      the reaction was 3.4(0.6)th order with respect to THF. Crystal and molecular
      structures of H2N-Zr[N(SiMe3)2]3 (2a) and 4a-b have been determined.

PMID- 15732995
TI  - XeF2 as a ligand in a coordination compound with the BF4- anion.
AB  - The first tetrafluoroborate compound with XeF2 coordinated to a metal center,
      [Cd(XeF2)](BF4)2, has been synthesized. It crystallizes in monoclinic space group
      P21/a with a = 8.785(11) A, b = 9.079(2) A, c = 10.718(6) A, beta = 110.824(6),
      and Z = 4. Its crystal structure and that of Cd(BF4)2 have been solved. The
      latter crystallizes in orthorhombic space group Pbca. Both syntheses were
      performed in aHF as solvent, at room temperature, yielding colorless solids. The
      Raman spectra of the solids are in harmony with the crystallographic findings.
      [Cd(XeF2)](BF4)2 has been shown to be in equilibrium with XeF2 and Cd(BF4)2 in
      aHF.

PMID- 15732994
TI  - Structural variations and spectroscopic properties of luminescent mono- and
      multinuclear silver(I) and copper(I) complexes bearing phosphine and cyanide
      ligands.
AB  - Reaction of equimolar amounts of AgCN and PCy3 gave the polymer
      [(Cy3P)Ag(NCAgCN)]infinity (1), whereas employment of excess PCy3 yielded the
      discrete compound [(Cy3P)2Ag(NCAgCN)] (2). Reacting
      bis(dicyclohexylphosphino)methane (dcpm) with AgCN in 1:1 and 1:2 molar ratios
      gave two crystalline forms, namely [Ag2(mu-dcpm)2][Ag(CN)2]2 x (CH3OH)2 (3a x
      (CH3OH)2) and [Ag2(mu-dcpm)2][Ag(CN)2]2 (3b), respectively. The similar reaction
      of CuCN with PCy3 afforded the polymeric compound [{(Cy3P)Cu(CN)}3]infinity (4),
      whereas treatment of CuCN with dcpm gave [Cu2(mu-dcpm)2(CN)2] (5). Employment of
      diphosphine ligands with longer -(CH2)n- spacers, such as 1,2
      bis(dicyclohexylphosphino)ethane (dcpe, n = 2) and 1,3
      bis(diphenylphosphino)propane (dppp, n = 3), in reactions with [Cu(CH3CN)4]PF6
      and KCN afforded the macrocylic compounds [{Cu(dcpe)}2(CN)(mu-dcpe)]PF6 (6(PF6))
      and [{Cu(dppp)}3(CN)2(mu-dppp)]PF6 (7(PF6)), respectively. The hexanuclear
      complex [Cu(CN)(PCy3)]6 (8) was obtained by reacting CuCN with PCy3 in the
      presence of sodium pyridine-2-thiolate. The UV-vis absorption spectrum of 1 in
      acetonitrile displays a weak shoulder at 245 nm (epsilon = 350 dm3 mol(-1) cm(
      1)). For 3a, 3b, and 5, the intense absorption bands at lambdamax = 257-276 nm
      with epsilon values of (1.73-1.80) x 10(4) dm3 mol(-1) cm(-1) are assigned to
      [ndsigma --> (n + 1)psigma] transitions. Complexes 3a and 3b emit at lambdamax =
      365 nm in CH3CN (quantum yield approximately 6 x10(-3), lifetime approximately
      0.2 micros). The solid-state emission of 5 (lambdamax = 470 and 488 nm at 298 and
      77 K) is red-shifted in energy from that of 4 (lambdamax = 401 and 405 nm at 298
      and 77 K, respectively). In 77 K MeOH/EtOH (1:4) glassy solution, complexes 4-8
      display intense emission with lambdamax at 382-416 nm, which is assigned to the
      [3d --> (4s, 4p)] triplet excited state.

PMID- 15732996
TI  - Methyl transfer reactivity of five-coordinate CH3CoIIIPc.
AB  - CH3CoIIIPc (Pc = dianion of phthalocyanine) has been characterized by equilibrium
      studies of its trans axial ligation and cyclic voltammetry as a relatively
      "electron poor" model of methylcobalamin, which in noncoordinating solvents
      persists as a five-coordinate complex. Axial base (N-donors, PBu3, SCN-, weakly
      binding O-donors) inhibition of methyl transfer from CH3CoIIIPc shows that the
      reaction proceeds via the reactive five-coordinate species, even in coordinating
      solvents. The virtual inactivity of six-coordinate CH3CoIIIPc(L) complexes
      provides a reference point for important biological processes.

PMID- 15732997
TI  - Difluoro complexes of platinum(II) and -(IV) with monodentate phosphine ligands:
      an exceptional stability of d6 octahedral organometallic fluorides.
AB  - Complexes (R3P)2PtF2 were prepared by reaction of the corresponding diiodo
      precursors with AgF in dichloromethane. The intermediate formation of trans- and
      cis-(R3P)2Pt(I)F was also observed. All fluoro complexes demonstrate a strong
      preference for the cis-configuration (R = Ph or Et) unless a bulky phosphine
      ligand is used (R = i-Pr), in which case the trans complex was observed. The
      Pt(IV) difluoro compounds (R3P)2Ar2PtF2 were obtained by reacting the Pt(II)
      diaryl precursors with XeF2. The fluoro ligands are located in the trans-position
      relative to the aryl groups in the overall octahedral environment. The
      representative Pt(II) and Pt(IV) difluoro complexes were characterized by X-ray
      crystallography. All fluoro compounds react rapidly with chlorotrimethylsilane to
      give the corresponding chloro complexes. The Pt(IV) difluorides are remarkably
      stable in the C-C reductive elimination reaction, relative to their dichloro
      analogs which reductively eliminate diaryl within several hours at 45 degrees C
      in N-methylpyrrolidone. It was found that phosphine dissociation from the
      octahedral Pt(IV) complex is essential for the reductive elimination reaction to
      take place, the difluoro complex being kinetically stable even at 60 degrees C.

PMID- 15732998
TI  - Homo- and heterobimetallic niobium(v) and tantalum(v) peroxo-tartrate complexes
      and their use as molecular precursors for Nb-Ta mixed oxides.
AB  - New water-soluble bimetallic peroxo-tartrato complexes of niobium(V) and/or
      tantalum(V) have been prepared, characterized from the structural and
      spectroscopic point of view, and used as molecular precursors for Nb-Ta mixed
      oxides. Two new homometallic complexes, (gu)5[Nb2(O2)4(tart)(Htart)] x 4H2O (1a)
      and (gu)6[Ta2(O2)4(tart)2] x 4H2O (2a), and the corresponding heterometallic
      complex, (gu)5[NbTa(O2)4(tart)(Htart)] x 4H2O (3), have been obtained. The
      crystal structures of the homometallic compounds, (gu)5[Nb2(O2)4(tart)(Htart)] x
      6H2O x 1H2O2 (1b) and (gu)6[Ta2(O2)4(tart)2] x 6H2O (2b), have been determined,
      showing, for both cases, two 8-fold-coordinated metal atoms, each surrounded by
      oxygen atoms belonging to two bidentate peroxides, two monodentate carboxylato,
      and two alkoxo groups from both bridging tartrato ligands. The coordination
      polyhedron around each metal atom is a dodecahedron. The thermal treatment of
      complexes 1a, 2a, and 3 in air at 700 or 800 degrees C, depending of the Ta
      content, provided Nb2O5, Ta2O5, and the solid solution TaNbO5, respectively. The
      thermal treatment of a 1:1 Nb/Ta molar ratio mixture of 1a and 2a has also been
      studied. BET and SEM measurements have been carried out and reveal these oxides
      possess relatively high specific surface areas and display a porous character.
      Comparison between the use of homo- and heterometallic precursors is discussed.

PMID- 15732999
TI  - Synthesis, crystal structure, and properties of multicomponent
      bis(ethylenedithio)tetrathiafulvalene charge-transfer salts of the [Mo3S7Br6]2-
      cluster.
AB  - A new family of bis(ethylenedithio)tetrathiafulvalene (ET) radical salts has been
      prepared in the presence of a triangular molybdenum sulfide cluster of formula
      [Mo3S7Br6]2-, which contains highly electrophilic axial sulfur atoms. A
      systematic change in the experimental conditions yields five different salts,
      namely (ETA)2(ETB)[Mo3S7Br6]2 x CH2Br2 (1), (ETA)(ETB)[Mo3S7Br6] x 1.1CH2Br2 (2),
      (ETA)(ETB)(ETC){[Mo3S7Br(6)]Br} x 0.5C2H4Cl2 (3), (ET)((n-Bu4)N)[Mo3S7Br6] (4),
      and (ET)(Ph4P)[Mo3S7Br6] x 0.5CH3CN (5), where the ET subscript denotes
      crystallographically independent molecules. The five compounds have been
      structurally characterized, and all of them crystallize in the triclinic space
      group P with Z = 2. Lattice parameters (A, deg) are the following: a = 11.762(4),
      b = 12.246(4), c = 16.813(6), alpha = 107.572(9), beta = 99.133(7), and gamma =
      102.856(8) for 1; a = 12.643(3), b = 13.370(4), c = 17.936(4), alpha =
      103.884(8), beta = 95.013(7), and gamma = 114.396(6) for 2; a = 11.907(6), b =
      12.742(6), c = 22.905(12), alpha = 90.053(15), beta = 79.063(14), and gamma =
      75.802(15) for 3; a = 12.787(6), b = 13.653(6), c = 17.543(8), alpha =
      68.398(10), beta = 69.911(12), and gamma = 62.377(10) for 4; a = 12.467(5), b =
      13.553(6), c = 18.913(8), alpha = 85.378(11), beta = 78.576(11), and gamma =
      65.858(9) for 5. Structural data combined with Raman spectral analysis shows
      that, in salt 1, one-third of the ET molecules, those marked as ETB, are
      incorporated into the structure as ET2+ and two-thirds as ET+. Bonds distances
      and Raman frequencies for donor molecules in compounds 2-5 suggest a 1+ charge
      for all ET molecules, in agreement with the stoichiometries and IR and electronic
      spectra of these salts. In all cases the various donor-cluster, donor-donor, and
      cluster-cluster interactions and those involving the solvent molecules give rise
      to unique arrangements of the donor molecules. A general feature of structures 1
      5 is the presence of alternating layers of dimerized organic donor molecules
      (ET+:ET+) and of inorganic clusters, where the long axis of the donor dimers runs
      almost parallel to the cluster layer. There is a strong tendency of the
      combination {[Mo3S7Br6]:ET} to accommodate a third bulky component. Compounds 4
      and 5 incorporate [(n-Bu4)N]+ or [Ph4P]+, respectively, with no apparent
      interactions with the ET layers in the solid state. Compound 2 and 4 are
      semiconductors, while the remaining salts are insulators.

PMID- 15733000
TI  - Unusual monodentate binding mode of 2,2'-dipyridylamine (L) in isomeric trans
      (acac)2RuII(L)2, trans-[(acac)2RuIII(L)2]ClO4, and cis-(acac)2RuII(L)2 (acac =
      acetylacetonate). synthesis, structures, and spectroscopic, electrochemical, and
      magnetic aspects.
AB  - The reaction of cis-Ru(acac)2(CH3CN)2 (acac = acetylacetonate) with 2,2'
      dipyridylamine (L) in ethanolic medium resulted in facile one-pot synthesis of
      stable [(acac)2RuIII(L)]ClO4 ([1]ClO4), trans-[(acac)2RuII(L)2] (2), trans
      [(acac)2RuIII)L)2]ClO4 ([2]ClO4), and cis-[(acac)2RuII(L)2] (3). The bivalent
      congener 1 was generated via electrochemical reduction of [1]ClO4. Although in
      [1]+ the dipyridylamine ligand (L) is bonded to the metal ion in usual bidentate
      fashion, in 2/[2]+ and 3, the unusual monodentate binding mode of L has been
      preferentially stabilized. Moreover, in 2/[2]+ and 3, two such monodentate L's
      have been oriented in the trans- and cis-configurations, respectively. The
      binding mode of L and the isomeric geometries of the complexes were established
      by their single-crystal X-ray structures. The redox stability of the Ru(II) state
      follows the order 1 < 2 << 3. In contrast to the magnetic moment obtained for
      [1]ClO4, mu = 1.84 muB at 298 K, typical for low-spin Ru(III) species, the
      compound [2]ClO4 exhibited an anomalous magnetic moment of 2.71 muB at 300 K in
      the solid state. The variable-temperature magnetic measurements showed a
      pronounced decrease of the magnetic moment with the temperature, and that dropped
      to 1.59 muB at 3 K. The experimental data can be fitted satisfactorily using eq 2
      that considered nonquenched spin-orbit coupling and Weiss constant in addition to
      the temperature-independent paramagnetism. [1]ClO4 and [2]ClO4 displayed rhombic
      and axial EPR spectra, respectively, in both the solid and the solution states at
      77 K.

PMID- 15733001
TI  - Control of electron acceptor ability with ligands (L) in photoinduced electron
      transfer from zinc porphyrin or zinc phthalocyanine to [Ru3(mu3-O)(mu
      CH3COO)6L3]+.
AB  - Photoinduced electron-transfer processes from the excited triplet states of zinc
      tetraphenylporphyrin (3ZnTPP*) or zinc tetra-tert-butylphthalocyanine (3ZnTBPc*)
      to oxo-acetato-bridged triruthenium clusters [Ru3(mu3-O)(mu-CH3CO2)6(L)3]+ have
      been confirmed by nanosecond laser flash photolysis in the visible and near-IR
      regions. The rise of the transient absorption spectra of the radical cations of
      ZnTPP and ZnTBPc and the reduced form of the oxo-acetato-bridged triruthenium
      cluster ([Ru3(mu3-O)(mu-CH3CO2)6(L)3]0) were observed with the concomitant decays
      of 3ZnTPP* or 3ZnTBPc*. The evaluated rate constants (kET) and quantum yields
      (PhiET) for electron-transfer were increased with the order of electron
      withdrawing ability of the ligands (L) coordinated to the Ru atoms, 4
      cyanopyridine > triphenylphosphine > pyridine > 4-(dimethylamino)pyridine, which
      is the order of promoting the electron-accepting ability of [Ru3(mu3-O)(mu
      CH3CO2)6(L)3]+. The PhiET values for 3ZnTPP* were lower than those for 3ZnTBPc*,
      suggesting the presence of competitive processes such as energy transfer process
      from 3ZnTPP* to the triplet states of [Ru3(mu3-O)(mu-CH3COO)6(L)3]+. For the back
      electron-transfer process, second-order kinetics indicates that the radical
      cations of ZnTPP or ZnTBPc and [Ru3(mu3-O)(mu-CH3COO)6(L)3]0 return to the
      original system after solvation in polar solvents at a diffusion controlled limit
      without side reactions, providing reversible photosensitizing intermolecular
      electron-transfer systems.

PMID- 15733002
TI  - Synthesis and characterization of a family of structurally characterized
      dysprosium alkoxides for improved fatigue-resistance characteristics of PDyZT
      thin films.
AB  - Using either an ammoniacal route, the reaction between DyCl3, Na0, and HOR in
      liquid ammonia, or preferentially reacting Dy(N(SiMe3)2)3 with HOR in a solvent,
      we isolated a family of dysprosium alkoxides as [Dy(mu-ONep)2(ONep)]4 (1),
      (ONep)2Dy[(mu3-ONep)(mu-ONep)Dy(ONep)(THF)]2(mu-ONep) (2), (ONep)2Dy[(mu3
      ONep)(mu-ONep)Dy(ONep)(py)]2(mu-ONep) (3), [Dy3(mu3-OBut)2(mu
      OBut3(OBut)4(HOBut)2] (4), [Dy3(mu3-OBut)2(mu-OBut)3(OBut)4(THF)2] (5), [Dy3(mu3
      OBut)2(mu-OBut)3(OBut)4(py)2] (6), (DMP)Dy(mu-DMP)4[Dy(DMP)2(NH3)]2 (7), [Dy(eta6
      DMP)(DMP)2]2 (8), Dy(DMP)3(THF)3 (9), Dy(DMP)3(py)3 (10), Dy(DIP)3(NH3)2 (11),
      [Dy(eta6-DIP)(DIP)2]2 (12), Dy(DIP)3(THF)2 (13), Dy(DIP)3(py)3 (14),
      Dy(DBP)3(NH3) (15), Dy(DBP)3 (16), Dy(DBP)3(THF) (17), Dy(DBP)3(py)2 (18), [Dy(mu
      TPS)(TPS2]2 (19), Dy(TPS)3(THF)3 (20), and Dy(TPS)3(py)3 (21), where ONep =
      OCH2CMe3, OBut) = OCMe3, DMP = OC6H3(Me)(2)-2,6, DIP = OC6H3(CHMe2)(2)-2,6, DBP =
      OC6H3(CMe3)(2)-2,6, TPS = OSi(C6H5)3, tol = toluene, THF = tetrahydrofuran, and
      py = pyridine. We were not able to obtain X-ray quality crystals of compounds 2,
      8, and 9. The structures observed and data collected for the Dy compounds are
      consistent with those reported for its other congeners. A number of these
      precursors were used as Dy dopants in Pb(Zr0.3Ti0.7)O3 (PZT 30/70) thin films,
      with compound 12 yielding the highest-quality films. The resulting
      Pb0.94Dy0.04(Zr0.3Ti0.7)O3 [PDyZT (4/30/70)] had similar properties to PZT
      (30/70), but showed substantial resistance to polarization reversal fatigue.

PMID- 15733003
TI  - Two stereoisomers of an S-bridged RhIII2PtII2 tetranuclear complex
      [{Pt(NH3)2}2{Rh(aet)3}2]4+ that lead to a discrete and a 1D RhIII2PtII2AgI
      structures by reacting with AgI (aet = 2-aminoethanethiolate).
AB  - An S-bridged RhIII2PtII2 tetranuclear complex having two nonbridging thiolato
      groups, [{Pt(NH3)2}2{Rh(aet)3}2]4+ ([1]4+), in which two fac(S)-[Rh(aet)3] units
      are linked by two trans-[Pt(NH3)2]2+ moieties, was synthesized by the 1:1
      reaction of fac(S)-[Rh(aet)3] (aet = 2-aminoethanethiolate) with trans
      [PtCl2(NH3)2] in water. Complex [1]4+ gave both the meso (DeltaLambda) and
      racemic (DeltaDelta/LambdaLambda) forms, which were separated by fractional
      crystallization. Of two possible geometries, syn and anti, which arise from the
      arrangement of two nonbridging thiolato groups, the meso and racemic forms of
      [1]4+ selectively afforded the anti and syn geometries, respectively. The
      DeltaLambda-anti and DeltaDelta/LambdaLambda-syn isomers of [1]4+ reacted with
      Ag+ using two nonbridging thiolato groups to produce a {RhIII2PtII2AgI}n)
      polymeric complex, {[Ag{Pt(NH3)2}2{Rh(aet)3}2]5+}n) ([2]5+), and a RhIII2PtII2AgI
      pentanuclear complex, [Ag{Pt2(mu-H2O)(NH3)2}{Rh(aet)3}2]5+ ([3]5+), respectively,
      which contain octahedral RhIII, square-planar PtII, and linear AgI centers. In
      [2]5+, each DeltaLambda-anti-[{Pt(NH3)2}2{Rh(aet)3}2]4+ tetranuclear unit is
      bound to two AgI atoms to form a one-dimensional zigzag chain, indicating the
      retention of the parental S-bridged structure in DeltaLambda-anti-[1]4+. In
      [3]5+, two Delta- or Lambda-fac(S)-[Rh(aet)3] units are linked by a [Pt2(mu
      H2O)(NH3)2]4+ dinuclear moiety, together with an AgI atom, indicating that two
      NH3 molecules in [1]4+ have been replaced by a water molecule that bridges two
      PtII centers, while the parental DeltaDelta/LambdaLambda-syn configuration is
      retained. The complexes obtained were characterized on the basis of electronic
      absorption, CD, and NMR spectra, along with single-crystal X-ray analyses.

PMID- 15733004
TI  - Efficient electroluminescence from new lanthanide (Eu3+, Sm3+) complexes.
AB  - The syntheses, structures, and electroluminescent properties are described for
      two new lanthanide complexes Ln(HFNH)3phen [HFNH = 4,4,5,5,6,6,6-heptafluoro-1-(2
      naphthyl)hexane-1,3-dione; phen = 1,10-phenanthroline; Ln = Eu3+ (1), Sm3+ (2)].
      Both complexes exhibit bright photoluminescence at room temperature (RT) due to
      the characteristic emission of Eu3+ and Sm3+ ion. Several devices using the two
      complexes as emitters were fabricated. The performances of these devices are
      among the best reported for devices using europium complex and samarium complex
      as emitters. The device based on 1 with the structure ITO/TPD (50 nm)/1:CBP (10%,
      40 nm)/BCP (20 nm)/AlQ (30 nm)/LiF (1 nm)/Al (200 nm) exhibits the maximum
      brightness of 957 cd/m2, current efficiency of 4.14 cd/A, and power efficiency of
      2.28 lm/W with a pure red Eu3+ ion emission. Especially, at the high brightness
      of 200 cd/m2, the device of 1 still has a high current efficiency of 2.15 cd/A.
      The device of 2 with a three-layer structure of ITO/TPD (50 nm)/2 (50 nm)/BCP (20
      nm)/LiF (1 nm)/Al (200 nm) gives the maximum brightness of 42 cd/m2, current
      efficiency of 0.18 cd/A. By the comparison of the electroluminescent properties
      of devices based on Eu(TTA3phen (TTA = 2-thenoyltrifluoroacteonate) and 1, we
      conclude that the polyfluoration on the alkyl group of the ligand and the
      introduction of the long conjugate naphthyl group into the ligand improve the
      efficiency of 1-doped devices, especially at high current densities.

PMID- 15733005
TI  - Reaction of copper(II) with ferrocene and 1,1'-dimethylferrocene in aqueous
      acetonitrile: the copper(II/I) self-exchange rate.
AB  - The kinetics of the reactions of copper(II) with ferrocene (Fc) and 1,1'
      dimethylferrocene (Dmfc) have been studied at 25 degrees C in aqueous
      acetonitrile (AN) containing 50-97.5 vol % AN. With increasing % AN, the rate
      constant increases along with the driving-force for the reaction. The results are
      analyzed in terms of Marcus theory to estimate the Cu(II/I) electron self
      exchange rate constant (k11) for the system. Over the solvent range studied, the
      calculated k11)changes from 1.1 x 10(-9) to 17 x 10(-9) M(-1) s(-1), with an
      average value of 5 x 10(-9). In addition, the structures of the
      trifluoromethanesulfonate salts of [Cu(AN)4]+, [Cu(OH2)2(AN)2]2+, and [Cu(AN)4]2+
      are reported. It is found that the Cu-NCCH3 bond-length difference between the
      Cu(I) and Cu(II) oxidation states is only approximately 0.02 A.

PMID- 15733006
TI  - Synthesis, characterization, and electrochemistry of biorelevant photosensitive
      low-potential orthometalated ruthenium complexes.
AB  - Redox potentials of photosensitive cyclometalated RuII derivatives of 2
      phenylpyridine or 2-(4-tolyl)pyridine are controllably decreased by up to 0.8 V
      within several minutes. This is achieved by irradiation of the ruthena(II)cycles
      cis-[Ru(o-X-2-py)(LL)(MeCN)2]PF6 (2, X = C6H4 (a) or 4-MeC6H3 (b), LL = 1,10
      phenanthroline or 2,2'-bipyridine). The cis geometry of the MeCN ligands has been
      confirmed by the X-ray structural studies. The sigma-bound sp2 carbon of the
      metalated ring is trans to LL nitrogen. Complexes 2 are made from [Ru(o-X-2
      py)(MeCN)4]PF6 (1) and LL. This "trivial" ligand substitution is unusual because
      1a reacts readily with phen in MeCN as solvent to give cis-[Ru(o-C6H4-2
      py)(phen)(MeCN)2]PF6 (2c) in a 83% yield, but bpy does not afford the bpy
      containing 2 under the same conditions. cis-[Ru(o-C6H4-2-py)(bpy)(MeCN)2]PF6 (2e)
      has been prepared in CH2Cl2 (74%). Studies of complexes 2c,e by cyclic
      voltammetry in MeOH in the dark reveal RuII/III quasy-reversible redox features
      at 573 and 578 mV (vs Ag/AgCl), respectively. A minute irradiation 2c and 2e
      converts them into new species with redox potentials of -230 and 270 mV,
      respectively. An exceptional potential drop for 2c is accounted for in terms of a
      photosubstitution of both MeCN ligands by methanol. ESR, 1H NMR, and UV-vis data
      indicate that the primary product of photolysis of 2c is an octahedral monomeric
      low-spin (S = 1/2) RuIII species, presumably cis-[RuIII(o-C6H4-2
      py)(phen)(MeOH)2]2+. The primary photoproduct of bpy complex 2e is cis-[RuII(o
      C6H4-2-py)(bpy)(MeCN)(MeOH)]+, and this accounts for a lower decrease in the
      redox potential. Irradiation of 2c in the presence of added chloride affords
      [(phen)(o-C6H4-2-py)ClRuIIIORuIVCl(o-C6H4-2-py)(phen)]PF6, a first mu-oxo-bridged
      mixed valent dimer with a cyclometalated unit. The structure of the dimer has
      been established by X-ray crystallography.

PMID- 15733007
TI  - Synthesis, characterization, and reactivity of Ti(IV)-monosubstituted Keggin
      polyoxometalates.
AB  - Ti(IV)-monosubstituted Keggin-type polyoxometalates (Ti-POMs), mu-oxo dimer
      [Bu4N]8[(PTiW11O39)2O] (1), and three monomers [Bu4N]4[PTi(L)W11O39], where L =
      OH (2), OMe (3), and OAr (4, ArOH = 2,3,6-trimethylphenol (TMP)), have been
      prepared starting from mu-hydroxo dimer [Bu4N]7[(PTiW11O39)2OH] (5) or
      heteropolyacid H5PW11TiO40 or both. The compounds have been characterized by
      elemental analysis, IR, UV-vis, and multinuclear (31P, 1H, 183W) NMR. The
      interaction of 1 and 3-5 with H2O in MeCN produces 2. The hydrolysis constants,
      estimated from 31P and 1H NMR data, are 0.006 and 0.04 for 1 and 3, respectively.
      Studies by 31P NMR, IR, potentiometric titration, and cyclic voltammetry revealed
      that 1-3 and 5 afford the same protonated titanium peroxo complex
      [Bu4N]4[HPTi(O2)W11O39] (I) upon interaction with aqueous H2O2 in MeCN. The rates
      of formation of I correlate with the rates of hydrolysis of the Ti-POMs and
      follow the order of 5 > 1 > 3. A two-step mechanism of the reaction of Ti-POMs
      with H2O2, which involves hydrolysis of the Ti-L bonds to yield 2 followed by
      fast interaction of 2 with hydrogen peroxide producing I, is suggested. The
      equilibrium constant for the reaction of 2 with H2O2 to yield I and H2O,
      estimated using 31P NMR, is 10. The interaction of the Ti-POMs with TMP follows
      the trends similar to their interaction with H2O) and requires preliminary
      hydrolysis of the Ti-L bonds. All of the Ti-POMs catalyze the oxidation of TMP
      with H2O2 in MeCN to give 2,3,5-trimethyl-p-benzoquinone and 2,2',3,3',5,5'
      hexamethyl-4,4'-biphenol. The product distribution is similar for all of the Ti
      POMs. The catalytic activities of the Ti-POMs correlate with the rates of
      formation of I and follow the order of 2 > 5 > 1 > 3. The findings lay a basis
      for a better understanding of the nature of the reactivity of titanium in Ti
      catalyzed oxidations.

PMID- 15733008
TI  - Pharmacological strategies to reduce cardiovascular risk in type 2 diabetes
      mellitus: an update.
AB  - Morbidity and mortality in patients with type 2 diabetes mellitus is largely
      dominated by the occurrence of cardiovascular disease (CVD). Treatment of known
      risk factors of CVD has proven to be beneficial in terms of reduction in risk of
      major CVD events in the general population. Recent trials have provided
      information on the treatment of hyperglycaemia, hypertension, dyslipidaemia and
      platelet aggregation in the patient with type 2 diabetes. Strict glycaemic
      control is not associated with a significant reduction in CVD risk, although new
      hypoglycaemic agents may offer additional benefits. In contrast, it has been
      demonstrated that treatment of hypertension and dyslipidaemia significantly
      reduce cardiovascular risk. Meticulous control of blood pressure to a level < or
      =130/80 mm Hg, preferably using renin-angiotensin system-modulating agents, is of
      proven value. Use of HMG-CoA reductase inhibitors (statins) as low-density
      lipoprotein (LDL)-cholesterol-lowering therapy, initiated at a level of > or
      =2.60 mmol/L is firmly established. Recent trials lend support to lowering the
      target level for LDL-cholesterol-lowering therapy to < or =1.81 mmol/L. Mainly
      based on risk analogy, international guidelines advocate the use of aspirin
      (acetylsalicylic acid) in the primary prevention of CVD in patients with type 2
      diabetes. However, there is no support from large trials that the estimated 25%
      risk reduction in primary prevention in a high-risk population is the same in the
      subgroup with diabetes. An intensified approach in order to identify and treat
      cardiovascular risk factors in patients with type 2 diabetes, stratified to
      individual patients, is necessary to reduce the excess cardiovascular burden of
      these patients.

PMID- 15733009
TI  - New treatment modalities for vitiligo: focus on topical immunomodulators.
AB  - The development of effective treatment modalities for vitiligo is dependent on an
      understanding of the events leading to depigmentation. However, the exact
      pathogenesis of vitiligo is still mostly unknown. Abnormalities in both humoral
      and cell-mediated immunity have been documented in vitiligo patients and they
      present a basis for using immunomodulating agents, such as corticosteroids and
      macrolide immunomodulators, in the treatment of vitiligo. Macrolide
      immunomodulators, such as tacrolimus and pimecrolimus, which can be used
      topically, are known as topical immunomodulators (TIMs). TIMs inhibit the action
      of calcineurin, and consequently inhibit T-cell activation and the production of
      various cytokines; this is considered the working mechanism of action of TIMs in
      vitiligo. Several small studies and case reports on the use of TIMs in vitiligo
      have been published so far. Tacrolimus achieves better results on the face and
      neck than on other body areas. Particular advantages of TIMs are safety in
      treating these areas because of lack of skin atrophy and good tolerability. The
      incidence of application site adverse events in vitiligo seems to be lower than
      in the treatment of atopic dermatitis. On the face and neck, TIMs may become a
      useful tool in the treatment of adults and children with vitiligo despite
      possibly lower efficacy than topical corticosteroids. Further, larger, controlled
      clinical studies are warranted to determine the definite role of TIMs as
      monotherapy or in combination with other modalities in the treatment of vitiligo.

PMID- 15733010
TI  - Adverse effects and drug interactions of antithrombotic agents used in prevention
      of ischaemic stroke.
AB  - Stroke is the third most common cause of death in the US. Primary prevention of
      stroke can be achieved by control of risk factors including hypertension,
      diabetes mellitus, elevated cholesterol levels and smoking. Approximately one
      third of all ischaemic strokes occur in patients with a history of stroke or
      transient ischaemic attack (TIA). The mainstay of secondary prevention of
      ischaemic stroke is the addition of medical therapy with antithrombotic agents to
      control the risk factors for stroke. Antithrombotic therapy is associated with
      significant medical complications, particularly bleeding.Low-dose aspirin
      (acetylsalicylic acid) has been shown to be as effective as high-dose aspirin in
      the prevention of stroke, with fewer adverse bleeding events. Aspirin has been
      shown to be as effective as warfarin in the prevention of noncardioembolic
      ischaemic stroke, with significantly fewer bleeding complications. Ticlopidine
      may be more effective in preventing stroke than aspirin, but is associated with
      unacceptable haematological complications. Clopidogrel may have some benefit over
      aspirin in preventing myocardial infarction, but has not been shown to be
      superior to aspirin in the prevention of stroke. The combination of clopidogrel
      and aspirin may be more effective than aspirin alone in acute coronary syndromes,
      but the incidence of adverse bleeding is significantly higher. Furthermore, the
      combination of aspirin with clopidogrel has not been shown to be more effective
      for prevention of recurrent stroke than clopidogrel alone, while the rate of
      bleeding complications was significantly higher with combination therapy. The
      combination of aspirin and extended-release dipyridamole has been demonstrated to
      be more effective than aspirin alone, with the same rate of adverse bleeding
      complications as low-dose aspirin. When selecting the appropriate antithrombotic
      agent for secondary prevention of stroke, the adverse event profile of the drug
      must be taken into account when assessing the overall efficacy of the treatment
      plan.

PMID- 15733011
TI  - An overview of economic evaluations for drugs used in rheumatoid arthritis :
      focus on tumour necrosis factor-alpha antagonists.
AB  - Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease that
      affects approximately 0.5-1% of the adult population. The introduction of new
      disease-modifying antirheumatic drugs (DMARDs) such as leflunomide, anakinra and
      the tumour necrosis factor (TNF)-alpha antagonists (infliximab, etanercept and
      adalimumab) have transformed the management of RA. In particular, the last class
      of agents has generated substantial controversy. Costing between 16,000 US
      dollars and 20,000 US dollars per patient-year (2001 values), the potential
      greater efficacy of treatment with TNFalpha antagonists comes at much higher drug
      costs, making these agents natural candidates for cost-effectiveness analyses
      (CEAs).A MEDLINE search (until 31 January 2004) identified six original CEAs
      evaluating TNFalpha antagonists in RA. The aim of a CEA is to facilitate the
      allocation of scarce health resources and to inform policy decisions. However, to
      enhance the reliability and relevance of these analyses to policy makers, there
      must be similarity between the methodologies used. Recently, the OMERACT (Outcome
      Measures in Rheumatoid Arthritis Clinical Trials) group produced a document to
      define such a reference case; the OMERACT document was used as a foundation to
      structure comparisons and highlight discrepancies. The methodologies employed in
      each analysis differed; in particular, disparate time horizons, comparators,
      quantities of drug and treatment sequences prohibit the comparison of cost
      effectiveness between studies. Outcomes also differed between the analyses. Most
      reported health-related quality of life (HR-QOL) in quality-adjusted life-years
      (QALYs). The QALYs metric was based on preference scores that were typically
      derived from linear regressions using the Health Assessment Questionnaire (HAQ).
      However, models also used American College of Rheumatology (ACR) criteria, as
      well as the disease activity score (DAS). Common to all studies was the lack of
      data from long-term randomised studies where efficacy and resource consumption in
      comparison with standard care has been investigated. As such, investigators
      combined short-term randomised control trial data with that of a long-term
      observational cohort, and modelled cost effectiveness over an appropriate time
      horizon. In addition, most analyses lacked rigorous sensitivity analysis to
      examine the impact of uncertainty in the parameters. Those analyses that examined
      time horizons of 6 months and 1 year published incremental cost-effectiveness
      ratios (ICERs) of 34,800 US dollars per ACR 70% response criteria (ACR70)
      weighted response (duration 6 months, 1999 values) and 96,166 US dollars
      (duration 1 year, 2002 values). Analyses that modelled costs and health outcomes
      beyond the first year reported ICER estimates ranging between 26,800 US dollars
      (patients' lifetime, 1998 values) and 40,308 US dollars (10 years, 2002 values).
      In terms of HR-QOL, the analyses reported incremental QALYs that ranged from
      0.116 (over 19 years) to 1.6 (over 10 years). Discounted costs of therapy ranged
      from 30,362 US dollars (10 years, 2002 values) to 93,000 US dollars (22 years,
      1998 values), and comparator costs ranged from 22,593 US dollars (10 years, 2002
      values) to 84,000 US dollars (22 years, 1998 values).

PMID- 15733013
TI  - Peginterferon alpha-2a (40KD) plus ribavirin: a review of its use in the
      management of patients with chronic hepatitis C and persistently 'normal' ALT
      levels.
AB  - Combination therapy with subcutaneous peginterferon alpha-2a (40KD) [Pegasys]
      plus oral ribavirin (Copegus) has been evaluated previously in patients with
      chronic hepatitis C and elevated ALT levels. A recent randomised, nonblind,
      multicentre trial examined the efficacy of this combination therapy in the
      treatment of patients with persistently 'normal' ALT levels. These trial results
      showed that combination therapy with peginterferon alpha-2a (40KD) plus ribavirin
      is effective in patients with chronic hepatitis C and persistently normal ALT
      levels. Overall, a sustained virological response occurred in over 50% of
      patients who received combination therapy for 48 weeks, albeit with a low daily
      dosage of ribavirin. The tolerability profile of combination therapy in patients
      with persistently normal ALT levels is similar to that seen in patients with
      elevated ALT levels. The decision as to whether or not treatment should be
      initiated in patients with chronic hepatitis C and persistently normal ALT levels
      should be made on an individual basis. If a decision is made to treat,
      combination therapy with peginterferon alpha-2a (40KD) plus ribavirin can be
      considered a first-line treatment option.

PMID- 15733014
TI  - Candesartan cilexetil: a review of its use in the management of chronic heart
      failure.
AB  - Candesartan cilexetil is the orally administered pro-drug of candesartan, a
      highly selective antagonist of the angiotensin II subtype 1 receptor that
      mediates the pressor activities of angiotensin II. Candesartan cilexetil is
      widely used for the treatment of hypertension and has recently been approved in
      Europe for the treatment of chronic heart failure (CHF) in patients with impaired
      left ventricular (LV) systolic function. Results of the CHARM (Candesartan in
      Heart failure: Assessment of Reduction in Mortality and morbidity) programme
      suggest that oral candesartan cilexetil reduces morbidity and mortality in
      patients with CHF and LV ejection fraction (LVEF) < or =40%. There are
      cardiovascular benefits when candesartan cilexetil is administered as an
      alternative to an ACE inhibitor, or as an add-on to current treatment regimens
      that include an ACE inhibitor, in symptomatic CHF. While tolerability is
      generally good, renal monitoring is required. The recent approval of candesartan
      cilexetil as both add-on and alternative therapy to ACE inhibitors in patients
      with CHF and impaired LV systolic function recognises the cardiovascular benefits
      of candesartan cilexetil in both types of treatment regimens.

PMID- 15733015
TI  - Paricalcitol: a review of its use in the management of secondary
      hyperparathyroidism.
AB  - Paricalcitol (Zemplar) is a synthetic vitamin D(2) analogue that inhibits the
      secretion of parathyroid hormone (PTH) through binding to the vitamin D receptor.
      It is approved in the US and in most European nations for intravenous use in the
      prevention and treatment of secondary hyperparathyroidism associated with chronic
      renal failure in adult, and in the US paediatric, patients. Paricalcitol
      effectively reduced elevated serum PTH levels and was generally well tolerated in
      children and adults with secondary hyperparathyroidism associated with chronic
      renal failure. In well designed clinical trials, paricalcitol was as effective as
      calcitriol and as well tolerated in terms of the incidence of prolonged
      hypercalcaemia and/or elevated calcium-phosphorus product (Ca x P). Thus,
      paricalcitol is a useful option for the management of secondary
      hyperparathyroidism in adults and children with chronic renal failure.

PMID- 15733012
TI  - Management of sight-threatening uveitis: new therapeutic options.
AB  - Over the past 2 decades therapy for the treatment of intraocular inflammation
      (uveitis) has developed into a highly differentiated approach with an increasing
      number of drug options. This paper primarily summarises literature from the past
      5 years (2000 to May 2004), gives an update on systemic immunosuppressive therapy
      for non-infectious uveitis and speculates about new developments that could
      become relevant in the near future for the treatment of uveitis patients. The
      spectrum of immunosuppressive drugs has been notably expanded by tumor necrosis
      factor inhibitors, but with some limitations to uveitis. Behcet's disease is an
      example of uveitis where a multisystem disorder can affect the eye very severely.
      This clinical example has been used to investigate the utility of many different
      types of immunosuppressive therapies and the clinical approach is extensively
      discussed in this review. An accompanying table summarises the proposed mode of
      action, standard dosage, common adverse effects, as well as estimated cost of
      current treatment options.

PMID- 15733016
TI  - 5-Lipoxygenase as a putative mechanism of NSAID-related psychiatric adverse
      events.

PMID- 15733017
TI  - Optimising treatment of elderly patients with ovarian cancer : improving their
      enrollment in clinical trials.
AB  - The aging population is the fastest growing segment of our population. Over the
      last century, the average life expectancy has increased by 25 years. The
      incidence of ovarian carcinoma, seen primarily in postmenopausal women, is,
      therefore, expected to increase. The current standard treatment of ovarian cancer
      has been determined on the basis of prospective, randomised clinical trials
      carried out by cooperative groups. Sixty-one percent of new cancer cases occur in
      women >65 years of age. Despite this fact, enrollment in clinical trials has been
      exceedingly low. In turn, this causes suboptimal treatment for a very fatal
      disease. The aetiology of this is multifactorial, and strategies for improvement
      are lacking. Elderly patients may be barred from participation based on physician
      biases alone. Elderly patients may have limited access to academic centres where
      clinical trials are conducted or be excluded on the basis of unrealistic
      inclusion criteria. As physicians, it is our duty to understand the elderly
      patient and the comorbidities in this age group that may influence the
      tolerability and toxicity of conventional therapies. Therefore, it is imperative
      that we make a conscious effort to examine ways in which we may improve
      enrollment of elderly women with ovarian cancer in clinical trials.

PMID- 15733018
TI  - Generalised anxiety disorder in elderly patients : epidemiology, diagnosis and
      treatment options.
AB  - Generalised anxiety disorder (GAD) is characterised by at least 6 months of
      excessive uncontrollable worry accompanied by symptoms of motor tension and
      vigilance and scanning. As with other anxiety disorders, GAD is less prevalent in
      older adults than younger adults. GAD has a high level of comorbidity with other
      psychiatric disorders and this has a bearing on estimates of its prevalence. GAD
      that is comorbid with another psychiatric disorder has a period prevalence of
      approximately 4% in community-dwelling older people. On the other hand, 'pure'
      GAD is less common, with a period prevalence of approximately 1%. Pure GAD in
      late life is a fairly even mix of chronic cases that began earlier in life and
      cases starting for the first time in later life. The most frequent and consistent
      finding regarding late-life generalised anxiety is its high level of comorbidity
      with major depression. There are few longitudinal data pertaining to the temporal
      association of generalised anxiety and major depression in late life, but the
      data that do exist suggest that the anxiety is frequently symptomatic of the
      depression. If generalised anxiety occurs exclusively during episodes of major
      depression, a separate diagnosis of GAD is not warranted. Cognitive behaviour
      therapy (CBT) is the most frequently studied psychological treatment for GAD.
      Although CBT is more effective than a wait-list control condition, it is not more
      effective than nondirective therapies in late-life GAD. Furthermore, a standard
      course of CBT appears to be less efficacious for GAD in older adults than younger
      adults. Further research is needed to develop more efficacious and specific forms
      of psychotherapy for late-life GAD. The three classes of medications that are
      most commonly used for GAD are: (i) antidepressants; (ii) benzodiazepines; and
      (iii) buspirone. Antidepressant medication is the pharmacological treatment of
      choice for most older adults with generalised anxiety. When generalised anxiety
      is secondary to an episode of major depression, the selection of an
      antidepressant is guided by the same principles that apply to treatment of
      nonanxious depression. Antidepressant medication is also effective for GAD in the
      absence of an episode of major depression. In this situation, citalopram and
      venlafaxine have been found to be efficacious in older people. Data from studies
      of mixed-aged patients suggest that escitalopram, paroxetine and trazodone may
      also be beneficial in late-life GAD. Despite their widespread use in older
      persons with anxiety, benzodiazepines have a limited role in the treatment of GAD
      in the elderly. If a benzodiazepine is initiated, pharmacokinetic considerations
      favour the use of either lorazepam or oxazepam. Buspirone also has a more limited
      role than antidepressants in the treatment of late-life GAD.

PMID- 15733019
TI  - Aspiration and infection in the elderly : epidemiology, diagnosis and management.
AB  - Aspiration of the oropharyngeal or gastric contents by elderly persons often
      leads to lower respiratory tract infections, such as aspiration pneumonia or
      pneumonitis. The existence of dysphagia and aspiration in elderly patients are
      important factors in the occurrence of aspiration pneumonia, but are not
      sufficient to cause aspiration pneumonia in the absence of other risk factors.
      Salivary flow and swallowing can eliminate Gram-negative bacilli from the
      oropharynx in healthy persons. However, elderly persons may have diminished
      production of saliva as a result of medications and oral/dental disease, leading
      to poor oral hygiene and oropharyngeal colonisation with pathogenic organisms.
      When dysphagic patients aspirate pathogenic bacteria while swallowing food or
      liquids, they must also have decreased defences, such as impaired immunity or
      pulmonary clearance, in order to develop aspiration pneumonia.Elderly patients
      with cerebrovascular disease often have dysphagia that leads to an increased
      incidence of aspiration. It was previously reported that patients with silent
      cerebral infarction affecting the basal ganglia were more likely to experience
      subclinical aspiration and an increased incidence of pneumonia. Basal ganglia
      infarction leads to the impairment of dopamine metabolism and, as a consequence,
      a decrease of substance P in the glossopharyngeal nerve and sensory vagal nerves.
      Therefore, dysphagia and a decreased cough reflex may be induced by the
      impairment of dopamine metabolism in some elderly patients with cerebrovascular
      disease, suggesting that pharmaceutical agents which modulate dopamine metabolism
      may be able to improve swallowing and the cough reflex in patients with basal
      ganglia infarction. The main strategy for controlling aspiration and aspiration
      related pulmonary infection in the elderly is to prevent aspiration of pathogenic
      bacteria along with the oropharyngeal or gastric contents. Because aspiration
      pneumonia in the elderly is related to certain risk factors, including dysphagia
      and aspiration, effective preventive measures involve various approaches, such as
      pharmacological therapy, swallowing training, dietary management, oral hygiene
      and positioning.

PMID- 15733020
TI  - Faecal incontinence in the elderly : epidemiology and management.
AB  - Faecal incontinence occurs in up to 10% of community dwelling persons > or = 65
      years of age and approximately 50% of nursing home residents. It is a vastly
      under-reported problem that has a devastating effect on those who experience it
      as well as their spouses and caregivers. There are three broad categories of
      faecal incontinence among the elderly: (i) overflow incontinence; (ii) reservoir
      incontinence; and (iii) rectosphincteric incontinence. The first two can be
      diagnosed based upon the patient's history and physical examination and the
      response to dietary and pharmacological interventions. The third is assessed by
      careful physical examination supplemented by diagnostic tests directed towards
      evaluation of anorectal continence mechanisms. The most important of these is
      anorectal manometry, which can be supplemented by studies of structure (anal
      ultrasonography or pelvic floor magnetic resonance imaging) and neuromuscular
      function (electromyogram). A variety of therapeutic interventions are employed in
      patients with rectosphincteric incontinence; these include dietary, behavioural,
      pharmacological and surgical modalities chosen on the basis of the results of
      diagnostic testing. For isolated internal anal sphincter weakness, a cotton
      barrier in the anal canal is often effective. Acute sphincter injury is best
      treated with sphincteroplasty but, otherwise, surgical procedures are of
      uncertain benefit. Peripheral neurogenic incontinence may be treated with
      antidiarrhoeal agents, biofeedback techniques and dietary manipulations. Sacral
      spinal nerve stimulation is a promising new technique for selected patients with
      neurogenic faecal incontinence and is currently undergoing testing in the US and
      Europe. Significant improvement in quality of life can be achieved in most
      elderly persons with faecal incontinence.

PMID- 15733021
TI  - Disease-modifying therapies for osteoarthritis : current status.
AB  - Osteoarthritis, the most common form of arthritis, is a debilitating progressive
      disease principally affecting the elderly. Osteoarthritis therapy has evolved in
      the past few decades from symptomatic treatment to possible disease-modifying
      solutions. In this paper, the pathophysiology of osteoarthritis is first
      reviewed, including an examination of the mechanisms underlying osteoarthritis
      and discussions of the roles of cartilage, synovial fluid and subchondral bone.
      The remainder of the paper discusses therapeutic approaches in current use and
      those in development, with special attention given to pharmacological treatments.
      Current approaches to treating osteoarthritis--i.e. medications;
      nonpharmacological modalities, such as physical therapy, exercise, weight
      management and orthotics; and (as a last resort) surgery--focus on reducing pain
      and improving (or at least maintaining) mobility. Drugs currently used to treat
      osteoarthritis fall into several categories: analgesics, NSAIDs, cyclo-oxygenase
      2 (COX-2) inhibitors, corticosteroids, viscosupplementation, and symptomatic slow
      acting drugs ('nutraceuticals'). The analgesics (paracetamol [acetaminophen] and
      opiates) have demonstrated less symptomatic efficacy than NSAIDs, while the
      latter have displayed mixed results in terms of joint space narrowing. COX-2
      inhibitors have been demonstrated to be equal to or superior to NSAIDs in
      effectiveness. However, once considered a safer alternative, COX-2 inhibitors
      have become the subject of intense scrutiny since recent clinical evidence has
      cast suspicion on their cardiovascular safety profile. Injectable therapies, such
      as corticosteroids and viscosupplementation have elicited favorable short-term
      response but no long-term structural modification. On the other hand, the slow
      acting drugs, especially chondroitin and glucosamine sulfate, have shown
      promising results. Also reviewed are other established and experimental therapies
      that seek to modify and/or even reverse the course of osteoarthritis. These
      include such medications as colchicine, bisphosphonates and hormones; dietary
      therapeutics, such as ginger extract and green tea; and such truly experimental
      treatments as matrix metalloproteinase inhibitors, cytokines, nitric oxide,
      growth factors and gene therapy. Osteoarthritis continues to be a difficult
      disorder to treat, as there is no cure as such and current treatments focus
      mainly on relieving pain and maintaining joint function. The search nevertheless
      continues for management regimens that can slow, alter or reverse the
      degenerative processes of osteoarthritis.

PMID- 15733023
TI  - Peripheral oedema related to quetiapine therapy : a case report.

PMID- 15733022
TI  - Poststroke aphasia : epidemiology, pathophysiology and treatment.
AB  - Aphasia, the loss or impairment of language caused by brain damage, is one of the
      most devastating cognitive impairments of stroke. Aphasia is present in 21-38% of
      acute stroke patients and is associated with high short- and long-term morbidity,
      mortality and expenditure. Recovery from aphasia is possible even in severe
      cases. While speech-language therapy remains the mainstay treatment of aphasia,
      the effectiveness of conventional therapies has not been conclusively proved.
      This has motivated attempts to integrate knowledge from several domains in an
      effort to plan more rational therapies and to introduce other therapeutic
      strategies, including the use of intensive language therapy and pharmacological
      agents. Several placebo-controlled trials suggest that piracetam is effective in
      recovery from aphasia when started soon after the stroke, but its efficacy
      vanishes in patients with chronic aphasia. Drugs acting on catecholamine systems
      (bromocriptine, dexamfetamine) have shown varying degrees of efficacy in case
      series, open-label studies and placebo-controlled trials. Bromocriptine is useful
      in acute and chronic aphasias, but its beneficial action appears restricted to
      nonfluent aphasias with reduced initiation of spontaneous verbal messages.
      Dexamfetamine improves language function in subacute aphasia and the beneficial
      effect is maintained in the long term, but its use is restricted to highly
      selected samples. Pharmacological agents operating on the cholinergic system
      (e.g. donepezil) have shown promise. Data from single-case studies, case series
      and an open-label study suggest that donepezil may have beneficial effects on
      chronic poststroke aphasia. Preliminary evidence suggests that donepezil is well
      tolerated and its efficacy is maintained in the long term. Randomised controlled
      trials of donepezil and other cholinergic agents in poststroke aphasia are
      warranted.

PMID- 15733024
TI  - Do selective cyclo-oxygenase-2 inhibitors have a future?
AB  - The dramatic withdrawal of rofecoxib on 30 September 2004, along with safety
      concerns about other cyclo-oxygenase (COX)-2 inhibitors (especially valdecoxib),
      raises important issues for clinicians, pharmaceutical companies and regulatory
      authorities. Some of these are examined in this article, including: (i) was the
      cardiotoxicity of rofecoxib evident long before its withdrawal?; (ii) is the
      thrombotic hazard a class effect that is applicable to all COX-2 inhibitors?;
      (iii) may conventional NSAIDs also confer a risk of cardiovascular thrombosis?;
      and (iv) is there any future for selective COX-2 inhibitors?

PMID- 15733026
TI  - Protease inhibitor-induced diabetic complications : incidence, management and
      prevention.
AB  - Protease inhibitors (PIs) have become a crucial element in the treatment of
      patients infected with HIV. However, the widespread use of PI therapy has also
      been associated with a number of metabolic adverse effects, including fat
      redistribution and hyperglycaemia. The objective of this review is a discussion
      of the incidence, pathophysiology, management and prevention of PI-associated
      hyperglycaemia. Initial case reports have been followed by large cross-sectional
      and cohort studies, which demonstrate that the incidence of PI-induced impaired
      glucose tolerance, as well as frank diabetes mellitus, is significant and demands
      attention. Investigations into the pathophysiology behind PI-associated
      hyperglycaemia have identified an underlying problem of insulin resistance that
      is presumably caused by both direct PI-induced mechanisms and lipotoxicity. Given
      this, clinical trials have explored the use of various classes of oral
      hypoglycaemic agents in the management of PI-induced diabetic complications, and
      the use of insulin therapy must be considered as well. Newer PI agents are also
      under development, with the hope of reducing metabolic adverse effects. In the
      meantime, prevention, in the form of dietary modification, regular physical
      activity and periodic screening for impaired glucose tolerance, must receive
      heightened attention in the care plan of patients receiving long-term PI therapy.

PMID- 15733027
TI  - Tolerability of paracetamol.
AB  - The excellent tolerability of therapeutic doses of paracetamol (acetaminophen) is
      a major factor in the very wide use of the drug. The major problem in the use of
      paracetamol is its hepatotoxicity after an overdose. Hepatotoxicity has also been
      reported after therapeutic doses, but critical analysis indicates that most
      patients with alleged toxicity from therapeutic doses have taken overdoses.
      Importantly, prospective studies indicate that therapeutic doses of paracetamol
      are an unlikely cause of hepatotoxicity in patients who ingest moderate to large
      amounts of alcohol. Controlled clinical trials have found that paracetamol is
      very well tolerated by the gastrointestinal tract. While variable results have
      been found in case control studies, most studies have shown no change or a small
      increase in the relative risk of perforations, ulcer or bleeding in the upper
      gastrointestinal tract. However, associations between the use of paracetamol and
      gastrointestinal toxicity, as well as with chronic renal disease and asthma, are
      very likely to reflect biases in some case control studies. In particular, such
      biases may be caused by the perceived high tolerability of paracetamol in these
      diseases. The consequent use of paracetamol in these diseases states then leads
      to an apparent association between paracetamol and the disease. Despite
      metabolism of paracetamol to reactive compounds, hypersensitivity reactions are
      rare, although urticaria occurs in occasional patients. Paracetamol appears to be
      well tolerated during pregnancy although prospective studies are required.

PMID- 15733028
TI  - Tibolone and endometrial cancer: a cohort and nested case-control study in the
      UK.
AB  - OBJECTIVE: Case series and spontaneous reports of endometrial cancer have raised
      the question as to whether the use of tibolone (introduced into the UK in 1991)
      is associated with an increased risk of endometrial cancer. This study set out to
      evaluate whether tibolone use is associated with an increased risk of endometrial
      cancer. METHODS: Age-adjusted incidence rate ratios (IRRs) of endometrial cancer
      were calculated for tibolone use compared with the use of other hormone
      replacement therapy (HRT). Separate sets of controls, matched for age and general
      practice, were compared with cases, all nested within a cohort of HRT users
      identified from the UK General Practice Research Database (GPRD). Conditional
      logistic regression analysis, adjusted for potential confounders, was used to
      study the association between tibolone use and the risk of endometrial cancer.
      RESULTS: 4995 women used tibolone as their first HRT product; 10 783 (4.3%) of
      the users of combined HRT had changed to tibolone at some time during the study
      period. Amongst women whose HRT began with tibolone, the age-adjusted IRR
      relative to those who started with combined sequential HRT was 1.83 (95% CI 1.19,
      2.82). The nested case-control study comprised 162 cases, each matched to two
      sets of 972 controls. There were 43 tibolone-exposed subjects, 28 of whom had
      used other HRT before or after tibolone. The adjusted odds ratio of the risk of
      endometrial cancer in women who had ever used tibolone, compared with users of
      combined sequential HRT, was 1.54 (95% CI 1.03, 2.32) in the age-matched set and
      1.58 (95% CI 1.01, 2.47) in the practice-matched set. Sensitivity analyses did
      not decrease the risk estimates found. DISCUSSION: Tibolone may be associated
      with an increased risk of endometrial cancer compared with conventional forms of
      HRT, but our data are fragile. Residual bias and uncontrolled confounding cannot
      be excluded, and follow-up time is insufficient to draw any firm conclusions with
      respect to the endometrial safety of tibolone.

PMID- 15733025
TI  - Extrapyramidal symptoms with atypical antipsychotics : incidence, prevention and
      management.
AB  - The treatment of schizophrenia changed drastically with the discovery of
      antipsychotic medications in the 1950s, the release of clozapine in the US in
      1989 and the subsequent development of the atypical or novel antipsychotics.
      These newer medications differ from their conventional counterparts, primarily
      based on their reduced risk of extrapyramidal symptoms (EPS). EPS can be
      categorised as acute (dystonia, akathisia and parkinsonism) and tardive (tardive
      dyskinesia and tardive dystonia) syndromes. They are thought to have a
      significant impact on subjective tolerability and adherence with antipsychotic
      therapy in addition to impacting function. Unlike conventional antipsychotic
      medications, atypical antipsychotics have a significantly diminished risk of
      inducing acute EPS at recommended dose ranges. These drugs may also have a
      reduced risk of causing tardive dyskinesia and in some cases may have the ability
      to suppress pre-existing tardive dyskinesia. This paper reviews the available
      evidence regarding the incidence of acute EPS and tardive syndromes with atypical
      antipsychotic therapy. Estimates of incidence are subject to several confounds,
      including differing methods for detection and diagnosis of EPS, pretreatment
      effects and issues surrounding the administration of antipsychotic medications.
      The treatment of acute EPS and tardive dyskinesia now includes atypical
      antipsychotic therapy itself, although other adjunctive strategies such as
      antioxidants have also shown promise in preliminary trials. The use of atypical
      antipsychotics as first line therapy for the treatment of schizophrenia is based
      largely on their reduced risk of EPS compared with conventional antipsychotics.
      Nevertheless, EPS with these drugs can occur, particularly when prescribed at
      high doses. The EPS advantages offered by the atypical antipsychotics must be
      balanced against other important adverse effects, such as weight gain and
      diabetes mellitus, now known to be associated with these drugs.

PMID- 15733029
TI  - Identification of priorities for medication safety in neonatal intensive care.
AB  - BACKGROUND: Although neonates are reported to be at greater risk of medication
      error than infants and older children, little is known about the causes and
      characteristics of error in this patient group. Failure mode and effects analysis
      (FMEA) is a technique used in industry to evaluate system safety and identify
      potential hazards in advance. The aim of this study was to identify and
      prioritize potential failures in the neonatal intensive care unit (NICU)
      medication use process through application of FMEA. METHODS: Using the FMEA
      framework and a systems-based approach, an eight-member multidisciplinary panel
      worked as a team to create a flow diagram of the neonatal unit medication use
      process. Then by brainstorming, the panel identified all potential failures,
      their causes and their effects at each step in the process. Each panel member
      independently rated failures based on occurrence, severity and likelihood of
      detection to allow calculation of a risk priority score (RPS). RESULTS: The panel
      identified 72 failures, with 193 associated causes and effects. Vulnerabilities
      were found to be distributed across the entire process, but multiple failures and
      associated causes were possible when prescribing the medication and when
      preparing the drug for administration. The top ranking issue was a perceived lack
      of awareness of medication safety issues (RPS score 273), due to a lack of
      medication safety training. The next highest ranking issues were found to occur
      at the administration stage. Common potential failures related to errors in the
      dose, timing of administration, infusion pump settings and route of
      administration. Perceived causes were multiple, but were largely associated with
      unsafe systems for medication preparation and storage in the unit, variable staff
      skill level and lack of computerised technology. CONCLUSION: Interventions to
      decrease medication-related adverse events in the NICU should aim to increase
      staff awareness of medication safety issues and focus on medication
      administration processes.

PMID- 15733031
TI  - Low doses of ionizing radiation and circulatory diseases: a systematic review of
      the published epidemiological evidence.
AB  - Recent analyses of mortality among atomic bomb survivors have suggested a linear
      dose-response relationship between ionizing radiation and diseases of the
      circulatory system for exposures in the range 0-4 Sv. If confirmed, this has
      substantial implications. We have therefore reviewed the published literature to
      see if other epidemiological data support this finding. Other studies allowing a
      comparison of the rates of circulatory disease in individuals drawn from the same
      population but exposed to ionizing radiation at different levels within the range
      0-5 Gy or 0-5 Sv were identified through systematic literature searches. Twenty
      six studies were identified. In some, disease rates among those exposed at
      different levels may have differed for reasons unrelated to radiation exposure,
      while many had low power to detect effects of the relevant magnitude. Among the
      remainder, one study found appreciable evidence that exposure to low-dose
      radiation was associated with circulatory diseases, but five others, all with
      appreciable power, did not. We conclude that the other epidemiological data do
      not at present provide clear evidence of a risk of circulatory diseases at doses
      of ionizing radiation in the range 0-4 Sv, as suggested by the atomic bomb
      survivors. Further evidence is needed to characterize the possible risk.

PMID- 15733032
TI  - A hypothesis: radiation-related leukemia is mainly attributable to the small
      number of people who carry pre-existing clonally expanded preleukemic cells.
AB  - Human leukemia frequently involves recurrent translocations. Since radiation is a
      well-known inducer of both leukemia and chromosomal translocations, it has long
      been suspected that radiation might cause leukemia by inducing specific
      translocations. However, recent studies clearly indicate that spontaneous
      translocations specific to acute lymphocytic leukemia (ALL) actually occur much
      more frequently than do leukemia cases with the same translocations. Moreover,
      the ALL-associated translocation-bearing cells are often found to have clonally
      expanded in individuals who do not develop ALL. Since radiation-induced DNA
      damage is generated essentially randomly in the genome, it does not seem likely
      that radiation could ever be responsible for the induction of identical
      translocations of relevance to ALL in multiple cells of an individual and hence
      be the primary cause of radiation-related leukemia. An alternative hypothesis
      described here is that the radiation-related ALL risk for a population is almost
      entirely attributable to a small number of predisposed individuals in whom
      relatively large numbers of translocation-carrying pre-ALL cells have
      accumulated. This preleukemic clone hypothesis explains various known
      characteristics of radiation-related ALL and implies that people who do not have
      substantial numbers of preleukemic cells (i.e. the great majority) are likely at
      low risk of developing leukemia. The hypothesis can also be applied to chronic
      myelogenous leukemia and to young-at-exposure cases of acute myelogenous
      leukemia.

PMID- 15733030
TI  - Prevalence of potentially severe drug-drug interactions in ambulatory patients
      with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy.
AB  - BACKGROUND: Drug-drug interactions (DDIs) are a well known risk factor for
      adverse drug reactions. HMG-CoA reductase inhibitors ('statins') are a
      cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are
      concomitantly treated with a variety of additional drugs. Since DDIs are
      associated with adverse reactions, we performed a cross-sectional study to assess
      the prevalence of potentially critical drug-drug and drug-statin interactions in
      an outpatient adult population with dyslipidaemia. METHODS: Data from patients
      with dyslipidaemia treated with a statin were collected from 242 practitioners
      from different parts of Switzerland. The medication list was screened for
      potentially harmful DDIs with statins or other drugs using an interactive
      electronic drug interaction program. RESULTS: We included 2742 ambulatory statin
      treated patients (mean age +/- SD 65.1 +/- 11.1 years; 61.6% males) with (mean +/
      SD) 3.2 +/- 1.6 diagnoses and 4.9 +/- 2.4 drugs prescribed. Of those, 190
      patients (6.9%) had a total of 198 potentially harmful drug-statin interactions.
      Interacting drugs were fibrates or nicotinic acid (9.5% of patients with drug
      statin interactions), cytochrome P450 (CYP) 3A4 inhibitors (70.5%), digoxin
      (22.6%) or ciclosporin (cyclosporine) [1.6%]. The proportion of patients with a
      potential drug-statin interaction was 12.1% for simvastatin, 10.0% for
      atorvastatin, 3.8% for fluvastatin and 0.3% for pravastatin. Additionally, the
      program identified 393 potentially critical non-statin DDIs in 288 patients.
      CONCLUSIONS: CYP3A4 inhibitors are the most frequent cause of potential drug
      interactions with statins. As the risk for developing rhabdomyolysis is increased
      in patients with drug-statin interactions, clinicians should be aware of the most
      frequently observed drug-statin interactions and how these interactions can be
      avoided.

PMID- 15733033
TI  - Radioadaptive response for protection against radiation-induced teratogenesis.
AB  - To clarify the characteristics of the radioadaptive response in mice, we compared
      the incidence of radiation-induced malformations in ICR mice. Pregnant ICR mice
      were exposed to a priming dose of 2 cGy (667 muGy/min) on day 9.5 of gestation
      and to a challenging dose of 2 Gy (1.04 Gy/min) 4 h later and were killed on day
      18.5 of gestation. The incidence of malformations and prenatal death and fetal
      body weights were studied. The incidence of external malformations was
      significantly lower (by approximately 10%) in the primed (2 cGy + 2 Gy) mice
      compared to the unprimed (2 Gy alone) mice. However, there were no differences in
      the incidence of prenatal death or the skeletal malformations or the body weights
      between primed and unprimed mice. These results suggest that primary conditioning
      with low doses of radiation suppresses radiation-induced teratogenesis.

PMID- 15733034
TI  - Catalase regulates cell growth in HL60 human promyelocytic cells: evidence for
      growth regulation by H(2)O(2).
AB  - Reactive oxygen species (ROS) including hydrogen peroxide (H(2)O(2)) are
      generated constitutively in mammalian cells. Because of its relatively long life
      and high permeability across membranes, H(2)O(2) is thought to be an important
      second messenger. Generation of H(2)O(2) is increased in response to external
      insults, including radiation. Catalase is located at the peroxisome and scavenges
      H(2)O(2). In this study, we investigated the role of catalase in cell growth
      using the H(2)O(2)-resistant variant HP100-1 of human promyelocytic HL60 cells.
      HP100-1 cells had an almost 10-fold higher activity of catalase than HL60 cells
      without differences in levels of glutathione peroxidase, manganese superoxide
      dismutase (MnSOD), and copper-zinc SOD (CuZnSOD). HP100-1 cells had higher
      proliferative activity than HL60 cells. Treatment with catalase or the
      introduction of catalase cDNA into HL60 cells stimulated cell growth. Exposure of
      HP100-1 cells to a catalase inhibitor resulted in suppression of cell growth with
      concomitant increased levels of intracellular H(2)O(2). Moreover, exogenously
      added H(2)O(2) or depletion of glutathione suppressed cell growth in HL60 cells.
      Extracellular signal regulated kinase 1/2 (ERK1/2) was constitutively
      phosphorylated in HP100-1 cells but not in HL60 cells. Inhibition of the ERK1/2
      pathway suppressed the growth of HP100-1 cells, but inhibition of p38 mitogen
      activated protein kinase (p38MAPK) did not affect growth. Moreover, inhibition of
      catalase blocked the phosphorylation of ERK1/2 but not of p38MAPK in HP100-1
      cells. Thus our results suggest that catalase activates the growth of HL60 cells
      through dismutation of H(2)O(2), leading to activation of the ERK1/2 pathway;
      H(2)O(2) is an important regulator of growth in HL60 cells.

PMID- 15733035
TI  - Cytotoxic and mutagenic effects of chronic low-dose-rate irradiation on TERT
      immortalized human cells.
AB  - To analyze the genetic effects of low-dose-rate radiation on human cells, we used
      human telomere reverse transcriptase (TERT)-immortalized fibroblast cells
      obtained from normal individuals. We studied the effect of low-dose-rate (0.3
      mGy/ min) and high-dose-rate (2 Gy/min) radiation on cells in a confluent state.
      Survival and micronucleus induction frequency showed higher resistance after
      irradiation at low dose rate than at high dose rate. The survival after 5 Gy of
      high-dose-rate radiation was 0.01 compared to 0.3 after low-dose-rate irradiation
      at the same dose. In accordance with this, the level of HPRT mutation induction
      by low-dose-rate radiation decreased to approximately one-eighth that for high
      dose-rate radiation. We then characterized the mutants by multiplex PCR analysis,
      which showed that the fraction of deletion mutations was lower in the mutant
      cells induced at low dose rate than at high dose rate. Furthermore, the size of
      the deletions in mutant cells induced by low-dose-rate radiation appeared to be
      smaller than those in mutant cells irradiated at high dose rate. Only a few exons
      were deleted in the former mutants while all exons were deleted in most of the
      latter mutants. The present study indicates that the genetic effects of low-dose
      rate radiation on nonproliferating normal human cells are quantitatively and
      qualitatively less severe than the effect of high-dose-rate radiation.

PMID- 15733036
TI  - Bystander effects may modulate ultraviolet A and B radiation-induced delayed
      mutagenesis.
AB  - Ultraviolet irradiation of cells can induce a state of genomic instability that
      can persist for several cell generations after irradiation. However, questions
      regarding the time course of formation, relative abundance for different types of
      ultraviolet radiation, and mechanism of induction of delayed mutations remain to
      be answered. In this paper, we have tried to address these questions using the
      hypoxanthine phosphoribosyl transferase (HPRT) mutation assay in V79 Chinese
      hamster cells irradiated with ultraviolet A or B radiation. Delayed HPRT(-)
      mutations, which are indications of genomic instability, were detected by
      incubating the cells in medium containing aminopterin, selectively killing HPRT(
      ) mutants, and then treating the cells with medium containing 6-thioguanine,
      which selectively killed non-mutant cells. Remarkably, the delayed mutation
      frequencies found here were much higher than reported previously using a cloning
      method. Cloning of cells immediately after irradiation prevents contact between
      individual cell clones. In contrast, with the present method, the cells are in
      contact and are mixed several times during the experiment. Thus the higher
      delayed mutation frequency measured by the present method may be explained by a
      bystander effect. This hypothesis is supported by an experiment with an inhibitor
      of gap junctional intercellular communication, which reduced the delayed mutation
      frequency. In conclusion, the results suggest that a bystander effect is involved
      in ultraviolet-radiation-induced genomic instability and that it may be mediated
      in part by gap junctional intercellular communication.

PMID- 15733037
TI  - Regulation of ultraviolet B radiation-mediated activation of AP1 signaling by
      retinoids in primary keratinocytes.
AB  - The main cause of skin cancer and photo-aging is chronic exposure to ultraviolet
      B (UVB) radiation. Such damage can be ameliorated by retinoid treatment. UVB
      radiation-induced skin carcinogenesis is associated with the induction of
      activator protein 1 (AP1) signaling and factors, namely FOS and JUN family
      members. We investigated the effects of several retinoids, all-trans-retinoic
      acid (tRA), 9-cis-retinoic acid (cRA), and N-(4-hydroxyphenyl)-retinamide (HPR),
      on UVB-induced damage in primary mouse keratinocytes. In addition, the interplay
      between UVB radiation, retinoid receptors, and AP1 signaling was assessed using
      Western blot analysis and ribonuclease protection and gene reporter assays.
      Exposure of keratinocytes to UVB radiation caused a down-regulation of the
      retinoid receptor protein levels in a proteasome-mediated manner. In contrast,
      FOS and JUN proteins were transiently induced shortly after exposure to UVB
      radiation. Retinoid treatment caused a dose-dependent reduction in the levels of
      retinoid receptor proteins. When irradiated cells were treated with retinoids, no
      significant effects on AP1 protein expression were noted. Interestingly,
      pretreatments with tRA and cRA, but not HPR, suppressed UVB-radiation-induced AP1
      activity by more than 50%, whereas post-treatment failed to produce similar
      effects. Our findings indicate that the inhibition of AP1 activity by retinoids
      explains, at least in part, the chemopreventive potential of retinoids in UV
      radiation-associated epidermal damage.

PMID- 15733038
TI  - The death-inducing effect and genomic instability.
AB  - Exposure to ionizing radiation can induce a heritable change in the unirradiated
      progeny of irradiated cells. This non-targeted effect of ionizing radiation
      manifests as genomic instability, and although there is some debate as to the
      role of genomic instability in the carcinogenic process, it is thought by some to
      be an early step in radiation carcinogenesis. Although the mechanism of induction
      of genomic instability is not clearly understood, evidence suggests that secreted
      factors from irradiated cells may be involved. We have previously identified
      another non-targeted effect of ionizing radiation, the death-inducing effect.
      Exposure of unirradiated GM10115 cells to medium from chromosomally unstable
      clones was generally found to be cytotoxic. However, occasionally cells will
      survive in medium from unstable clones and can be clonally expanded. The absolute
      yield of survivors is independent of the initial number of cells plated when cell
      densities reached 5,000 or more cells/dish. After cytogenetic analysis of the
      surviving colonies, we found chromosomal instability in three of 40 clones
      analyzed, while some clones exhibited increased micronucleus frequency and HPRT
      mutation frequency. These data suggest that our chromosomally unstable GM10115
      cells secrete factors that are cytotoxic to the majority of stable, parental
      cells but are also capable of inducing a heritable change in some of the
      survivors that can manifest as delayed genomic instability. These results suggest
      a mechanism whereby instability can be perpetuated through the influences of
      potentially cytotoxic factors produced by genomically unstable clones.

PMID- 15733039
TI  - Variation in apoptosis profiles in radiation-induced genomically unstable cell
      lines.
AB  - Delayed reproductive cell death or lethal mutations in the survivors of
      irradiated cells is a well-characterized end point associated with radiation
      induced genomic instability. Although the mechanism for this delayed lethality
      has not been identified, it is thought to be a means of eliminating cells that
      have sustained extensive damage, thus preventing tissue disruption after
      radiation exposure. In this study we have tested the hypothesis that delayed
      reproductive cell death in chromosomally unstable GM10115 clones is due to
      persistently increased levels of apoptosis. Evidence for differences in apoptosis
      in two representative genomically unstable clones after irradiation is presented.
      In addition, one of the unstable clones was found to have abnormal levels of
      apoptosis after radiation exposure. An understanding of apoptosis in genomically
      unstable clones may provide insight into the maintenance of genomic instability
      and the mechanism by which genomically unstable cells evade cell death,
      potentially contributing to carcinogenesis.

PMID- 15733040
TI  - Low-dose binary behavior of bystander cell killing after microbeam irradiation of
      a single cell with focused c(k) x rays.
AB  - Although conclusive evidence has been obtained for the presence of radiation
      induced bystander effects, the mechanisms that trigger and regulate these
      processes are still largely unknown. The bystander effect may play a critical
      role in determining the biological effectiveness of low-dose exposures, but
      questions on how to incorporate it into current models and extrapolate the risks
      of radiation-induced carcinogenesis are still open. The Gray Cancer Institute
      soft X-ray microbeam has been used to investigate the dose-response relationship
      of the bystander effect below 0.5 Gy. The survival response of V79 cells was
      assessed after the irradiation of a single cell within a population with a
      submicrometer-size beam of carbon K X rays (278 eV). Above 0.3 Gy, the measured
      bystander cell killing was in agreement with previously published data; however,
      a significant increase in the scatter of the data was observed in the low-dose
      region (<0.3 Gy). The data distribution observed indicates a binary behavior for
      triggering of the bystander response. According to our hypothesis, the
      probability of triggering a bystander response increases approximately linearly
      with the dose delivered to the single selected cell, reaching 100% above about
      0.3 Gy. The magnitude of the bystander effect, when triggered, is approximately
      constant with the dose and results in an overall approximately 10% reduction in
      survival in our system. This suggests that the event that triggers the emission
      of the bystander signal by the hit cell is an all-or-nothing process.
      Extrapolation of the data indicates that when a single fast electron traverses a
      V79 cell, there is a probability of approximately 0.3% that the cell will emit
      the bystander signal. The data presented in this paper have also been analyzed
      statistically to test the possibility that complex DNA double-strand breaks may
      be the initial critical event.

PMID- 15733041
TI  - A model of cytokine shedding induced by low doses of gamma radiation.
AB  - A model for sustained shedding of epidermal growth factor (EGF) in response to
      low doses of gamma radiation was developed based on a time delay in the feedback
      from mitogen-activated protein kinase (MAPK) activation to metalloprotease
      activity in an autocrine signaling process. We determined the kinetic parameters
      of our model using the data available for MAPK activation by gamma irradiation in
      the 1-2-Gy dose range and then showed that predictions of the model were
      consistent with experimental results for the kinetics of EGF shedding into the
      growth medium after exposure of human mammary epithelial cells to 1-5 cGy of
      gamma radiation in the presence of antibodies that block ligand binding to EGF
      receptors. The model allowed us to estimate the rate of radiation-induced
      cytokine release per cell from measurements of EGF concentration in the growth
      medium and to assess the effectiveness of EGF shedding and subsequent diffusion
      through the medium as a mechanism for signal transmission between hit cells and
      bystanders.

PMID- 15733042
TI  - Production and validation of CR-39-based dishes for alpha-particle
      radiobiological experiments.
AB  - The study of radiobiological effects induced in vitro by low fluences of alpha
      particles would be significantly enhanced if the precise localization of each
      particle track in the cell monolayer was known. From this perspective, we
      developed a new method based on tailor-made UV-radiation-cured CR-39, the
      production of which is described. Its validation both as a petri dish and as
      solid-state nuclear track detectors is demonstrated. With respect to the demands
      on solid-state nuclear track detectors in such experiments, these biologically
      compatible detectors have a controlled micrometric thickness that allows them to
      be crossed by the alpha particles. In this study, we present a method for
      obtaining 10-mum-thick CR-39, its chemical characterization, and its properties
      as a solid-state nuclear track detector under the environmental conditions of
      radiobiological experiments. The experimental studies performed with 3.5 MeV
      alpha particles show that their transmitted energy is sufficient enough to cross
      the entire cellular volume. Under optimal conditions, etched tracks are clearly
      defined 2 h after etching. Moreover, the UV-radiation-cured CR-39 represents an
      essentially zero background that is due to the short time between the production
      and use of the polymer. Under a confocal microscope, this thin solid-state
      nuclear track detector allows the precise localization of the impact parameter at
      the subcellular level.

PMID- 15733043
TI  - The use of ELISA to monitor amplified hemolysis by the combined action of osmotic
      stress and radiation: potential applications.
AB  - A new assay has been developed to study the osmotic fragility of red blood cells
      (RBCs) and the involvement of oxygen-derived free radicals and other oxidant
      species in causing human red blood cell hemolysis. The amount of hemoglobin
      released into the supernatant, which is a measure of human red blood cell
      hemolysis, is monitored using an ELISA reader. This ELISA-based osmotic fragility
      test compared well with the established osmotic fragility test, with the added
      advantage of significantly reduced time and the requirement of only 60 mul of
      blood. This small amount of blood was collected fresh by finger puncture and was
      immediately diluted 50 times with PBS, thus eliminating the use of anticoagulants
      and the subsequent washings. Since exposure of RBCs to 400 Gy gamma radiation
      caused less than 5% hemolysis 24 h after irradiation, the RBC hemolysis induced
      by gamma radiation was amplified by irradiating the cell in hypotonic saline. The
      method was validated by examining the protective effect of Trolox, an analog of
      vitamin E and reduced glutathione (GSH), a well-known radioprotector, against
      human RBC hemolysis caused by the combined action of radiation and osmotic
      stress. Trolox, a known membrane stabilizer and an antioxidant, and GSH offered
      significant protection. This new method, which is simple and requires
      significantly less time and fewer RBCs, may offer the ability to study the
      effects of antioxidants and membrane stabilizers on human red blood cell
      hemolysis induced by radiation and oxidative stress and assess the osmotic
      fragility of erythrocytes.

PMID- 15733044
TI  - Proteome alterations in gamma-irradiated human T-lymphocyte leukemia cells.
AB  - Analyses of the protein expression profiles of irradiated cells may be beneficial
      for identification of new biomolecules of radiation-induced cell damage.
      Therefore, in this study we exploited the proteomic approach to identify proteins
      whose expression is significantly altered in gamma-irradiated human T-lymphocyte
      leukemia cells. MOLT-4 cells were irradiated with 7.5 Gy and the cell lysates
      were collected at different times after irradiation (2, 5 and 12 h). The proteins
      were separated by two-dimensional electrophoresis and quantified using an image
      evaluation system. Proteins exhibiting significant radiation-induced alterations
      in abundance were identified by peptide mass fingerprinting. We identified 14
      proteins that were either up- or down-regulated. Cellular levels of four of the
      proteins (Rho GDP dissociation inhibitor 1 and 2, Ran binding protein 1,
      serine/threonine protein kinase PAK2) were further analyzed by two-dimensional
      immunoblotting to confirm the data obtained from proteome analysis. All
      identified proteins were classified according to their cellular function,
      including their participation in biochemical and signaling pathways. Taken
      together, our results suggest the feasibility of the proteome method for
      monitoring of cellular radiation responses.

PMID- 15733045
TI  - Research in low back pain: time to stop seeking the elusive "magic bullet".

PMID- 15733046
TI  - Trunk muscle stabilization training plus general exercise versus general exercise
      only: randomized controlled trial of patients with recurrent low back pain.
AB  - BACKGROUND AND PURPOSE: The purpose of this randomized controlled trial was to
      examine the usefulness of the addition of specific stabilization exercises to a
      general back and abdominal muscle exercise approach for patients with subacute or
      chronic nonspecific back pain by comparing a specific muscle stabilization
      enhanced general exercise approach with a general exercise-only approach.
      SUBJECTS: Fifty-five patients with recurrent, nonspecific back pain
      (stabilization-enhanced exercise group: n=29, general exercise-only group: n=26)
      and no clinical signs suggesting spinal instability were recruited. METHODS: Both
      groups received an 8-week exercise intervention and written advice (The Back
      Book). Outcome was based on self-reported pain (Short-Form McGill Pain
      Questionnaire), disability (Roland-Morris Disability Questionnaire), and
      cognitive status (Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia,
      Pain Locus of Control Scale) measured immediately before and after intervention
      and 3 months after the end of the intervention period. RESULTS: Outcome measures
      for both groups improved. Furthermore, self-reported disability improved more in
      the general exercise-only group immediately after intervention but not at the 3
      month follow-up. There were generally no differences between the 2 exercise
      approaches for any of the other outcomes. DISCUSSION AND CONCLUSION: A general
      exercise program reduced disability in the short term to a greater extent than a
      stabilization-enhanced exercise approach in patients with recurrent nonspecific
      low back pain. Stabilization exercises do not appear to provide additional
      benefit to patients with subacute or chronic low back pain who have no clinical
      signs suggesting the presence of spinal instability.

PMID- 15733047
TI  - Canadian physical therapists' interest in web-based and computer-assisted
      continuing education.
AB  - BACKGROUND AND PURPOSE: Distance education via computer-assisted learning (CAL),
      including Web-based and CD-ROM learning, confers a number of advantages compared
      with traditional learning methods. The purposes of this study were (1) to
      determine the interest of Canadian physical therapists in participating in
      continuing education using CAL methods and (2) to determine whether interest in
      CAL was related to type of employment, area of practice, education, computer
      skill and access, and other demographic variables. SUBJECTS AND METHODS: A random
      sample of Canadian physical therapists and all members of cardiopulmonary
      interest groups were surveyed. RESULTS: Of 1,426 survey questionnaires mailed, 69
      were returned (58 were unopened and 11 were duplicates). From the remaining 1,357
      potential survey responses, 757 responses were received, for an overall response
      rate of 56%. Seventy-eight percent of the respondents indicated their interest in
      participating in CAL. Factors associated with interest in CAL included 2 or more
      hours of Internet access per week, Internet access at both home and work,
      computer skill, education level, practice area, and belonging to a
      cardiopulmonary interest group. DISCUSSION AND CONCLUSION: The findings indicate
      a large positive interest in CAL. Increasing CAL continuing education
      opportunities could increase options for physical therapists to meet professional
      expectations for continuing competency.

PMID- 15733048
TI  - Physical therapy interventions for patients with stroke in inpatient
      rehabilitation facilities.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to describe physical
      therapy provided to patients with stroke in inpatient rehabilitation facilities.
      SUBJECTS AND METHODS: Data were collected from 972 patients with stroke receiving
      physical therapy services at 6 rehabilitation facilities in the United States.
      Descriptive statistics were derived to describe physical therapy sessions,
      including proportion of therapy time spent in specific functional activities and
      proportion of those activities that included any of 59 interventions. RESULTS:
      Mean length of stay was 18.7 days (SD=10.3), and patients received physical
      therapy, on average, 13.6 days (SD=7.8). Patients attended, on average, 1.5
      (SD=0.3) physical therapy sessions per day, with each session lasting 38.1
      minutes (SD=17.1). Gait and prefunctional activities were performed most
      frequently (31.3% and 19.7% of total treatment time, respectively). For gait
      activity, physical therapists used balance and postural awareness training in
      more than 50% of sessions and used strength training for more than 50% of
      sessions of prefunctional activities. Eighty-six percent of the patients received
      evaluation, and 84% of the patients and families received education. DISCUSSION
      AND CONCLUSION: Therapists selected an eclectic approach to intervention rather
      than specific intervention techniques. The approach to patients' care included
      interventions to remediate impairments and to compensate for functional
      limitations. Therapists also reported frequently using motor control and motor
      learning approaches to facilitate all activities. This approach to care is
      largely consistent with existing stroke care guidelines and advances in the
      scientific theories of motor control and motor learning.

PMID- 15733050
TI  - The kappa statistic in reliability studies: use, interpretation, and sample size
      requirements.
AB  - PURPOSE: This article examines and illustrates the use and interpretation of the
      kappa statistic in musculoskeletal research. SUMMARY OF KEY POINTS: The
      reliability of clinicians' ratings is an important consideration in areas such as
      diagnosis and the interpretation of examination findings. Often, these ratings
      lie on a nominal or an ordinal scale. For such data, the kappa coefficient is an
      appropriate measure of reliability. Kappa is defined, in both weighted and
      unweighted forms, and its use is illustrated with examples from musculoskeletal
      research. Factors that can influence the magnitude of kappa (prevalence, bias,
      and non-independent ratings) are discussed, and ways of evaluating the magnitude
      of an obtained kappa are considered. The issue of statistical testing of kappa is
      considered, including the use of confidence intervals, and appropriate sample
      sizes for reliability studies using kappa are tabulated. CONCLUSIONS: The article
      concludes with recommendations for the use and interpretation of kappa.

PMID- 15733049
TI  - Bone mineral density during total contact cast immobilization for a patient with
      neuropathic (Charcot) arthropathy.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus (DM)-related neuropathic arthropathy of
      the foot is a destructive bone and joint process. The effect of cast
      immobilization and non-weight bearing on bone loss has not been well studied. The
      purpose of this case report is to describe the changes in bone mineral density
      (BMD) of the calcaneus in the feet of a patient with acute neuropathic
      arthropathy during total contact cast immobilization. CASE DESCRIPTION: The
      patient was a 34-year-old woman with type 1 DM, renal failure requiring dialysis,
      and a 7-week duration of neuropathic arthropathy of the midfoot. Intervention
      included total contact casting and minimal to no weight bearing for 10 weeks,
      with transition to therapeutic footwear. Ultrasound-derived estimates of BMD were
      taken of both involved and uninvolved calcanei. OUTCOME: Bone mineral density
      decreased for the involved foot (from 0.25 g/cm(2) to 0.20 g/cm(2)) and increased
      for the uninvolved foot (from 0.27 g/cm(2) to 0.31 g/cm(2)) during casting.
      DISCUSSION: The low initial BMD and further loss during casting suggest the need
      for transitional bracing and a well-monitored return to full activity to minimize
      the risk of recurrence and progression of foot deformity.

PMID- 15733051
TI  - Evaluation of female pelvic-floor muscle function and strength.
AB  - Evaluation of pelvic-floor muscle (PFM) function and strength is necessary (1) to
      be able to teach and give feedback regarding a woman's ability to contract the
      PFM and (2) to document changes in PFM function and strength throughout
      intervention. The aims of this article are to give an overview of methods to
      assess PFM function and strength and to discuss the responsiveness, reliability,
      and validity of data obtained with the methods available for clinical practice
      and research today. Palpation, visual observation, electromyography, ultrasound,
      and magnetic resonance imaging (MRI) measure different aspects of PFM function.
      Vaginal palpation is standard when assessing the ability to contract the PFM.
      However, ultrasound and MRI seem to be more objective measurements of the lifting
      aspect of the PFM. Dynamometers can measure force directly and may yield more
      valid measurements of PFM strength than pressure transducers. Further research is
      needed to establish reliability and validity scores for imaging techniques.
      Imaging techniques may become important clinical tools in future physical
      therapist practice and research to measure both pathophysiology and impairment of
      PFM dysfunction.

PMID- 15733052
TI  - Estimation of the left ventricular relaxation time constant tau requires
      consideration of the pressure asymptote.
AB  - The left ventricular isovolumic pressure decay, obtained by cardiac
      catheterization, is widely characterized by the time constant tau of the
      exponential regression p(t)=Pomega+(P0-Pomega)exp(-t/tau). However, several
      authors prefer to prefix Pomega=0 instead of coestimating the pressure asymptote
      empirically; others present tau values estimated by both methods that often lead
      to discordant results and interpretation of lusitropic changes. The present study
      aims to clarify the relations between the tau estimates from both methods and to
      decide for the more reliable estimate. The effect of presetting a zero asymptote
      on the tau estimate was investigated mathematically and empirically, based on
      left ventricular pressure decay data from isolated ejecting rat and guinea pig
      hearts at different preload and during spontaneous decrease of cardiac function.
      Estimating tau with preset Pomega=0 always yields smaller values than the
      regression with empirically estimated asymptote if the latter is negative and
      vice versa. The sequences of tau estimates from both methods can therefore
      proceed in reverse direction if tau and Pomega change in opposite directions
      between the measurements. This is exemplified by data obtained during an
      increasing preload in spontaneously depressed isolated hearts. The estimation of
      the time constant of isovolumic pressure fall with a preset zero asymptote is
      heavily biased and cannot be used for comparing the lusitropic state of the heart
      in hemodynamic conditions with considerably altered pressure asymptotes.

PMID- 15733055
TI  - Sphingosine 1-phosphate analogue recognition and selectivity at S1P4 within the
      endothelial differentiation gene family of receptors.
AB  - Synergistic computational and experimental studies provided previously unforeseen
      details concerning the structural basis of S1P (sphingosine 1-phosphate)
      recognition by the S1P4 G-protein-coupled receptor. Similarly to reports on the
      S1P1 receptor, cationic and anionic residues in the third transmembrane domain
      (R3.28 and E3.29 at positions 124 and 125) form ion pairs with the phosphate and
      ammonium of S1P, and alanine mutations at these positions abolished specific S1P
      binding, S1P-induced receptor activation and cell migration. Unlike findings on
      the S1P1 receptor, no cationic residue in the seventh transmembrane domain
      interacts with the phosphate. Additionally, two previously undiscovered
      interactions with the S1P polar headgroup have been identified. Trp186 at
      position 4.64 in the fourth transmembrane domain interacts by a cation-pi
      interaction with the ammonium group of S1P. Lys204 at position 5.38 forms an ion
      pair with the S1P. The S1P4 and S1P1 receptors show differences in binding-pocket
      shape and electrostatic distributions that correlate with the published structure
      activity relationships. In particular, the binding pocket of mS1P4 (mouse S1P4)
      has recognition sites for the anionic phosphate and cationic ammonium groups that
      are equidistant from the end of the non-polar tail. In contrast, the binding
      pocket of hS1P1 (human S1P4) places the ammonium recognition site 2 A (1 A=0.1
      nm) closer to the end of the non-polar tail than the phosphate recognition site.

PMID- 15733056
TI  - Tolerance of the Rieske-type [2Fe-2S] cluster in recombinant ferredoxin BphA3
      from Pseudomonas sp. KKS102 to histidine ligand mutations.
AB  - BphA3 from Pseudomonas sp. KKS102 is a Rieske-type [2Fe-2S] ferredoxin that
      transfers electrons from an NADH-dependent oxidoreductase, BphA4, to a biphenyl
      dioxygenase complex. A high-level expression and purification system for the
      recombinant BphA3 in Escherichia coli was constructed. Two histidine ligands of
      the Rieske-type cluster in BphA3, were each replaced with serine, cysteine,
      asparagine and tyrosine. The single mutants, in which either His44 or His65 was
      replaced with a cysteine residue (CH and HC mutants respectively), and the double
      mutant, in which both histidine residues were replaced with cysteine residue (CC
      mutant), accumulated to high levels in the E. coli cells, while the other single
      mutants did not. The purified WT (wild-type) protein showed characteristic near
      UV and visible absorption and CD spectra of Rieske-type clusters. The X-ray
      absorption spectra were suggestive of the existence of [2Fe-2S] clusters, with
      one histidine and three cysteine ligands in the CH and HC mutants, and an [2Fe
      2S] cluster with four cysteine ligands in the CC mutant. The BphA4-dependent
      cytochrome c reductase activities of the mutants were less than 0.3% of that of
      the WT protein. The redox potential of the WT protein determined by cyclic
      voltammetry was -180+/-5 mV compared with the standard hydrogen electrode, and
      that of the CH mutant was approx. 175 mV lower. The changes in the near-UV and
      visible absorption spectra of the mutants showed that the reduced iron-sulphur
      clusters in the mutants were unstable. His44 and His65 in BphA3 can be replaced
      with cysteine residues, but are required for the stabilization of the reduced
      form of the cluster.

PMID- 15733057
TI  - Activation of A431 human carcinoma cell motility by extracellular high-mobility
      group box 1 protein and epidermal growth factor stimuli.
AB  - HMGB1 (high-mobility group box 1) protein, a pleiotropic cytokine released by
      several cell types under physiological and pathological conditions, has been
      identified as a signal molecule active on A431 cells. Although extracellular
      HMGB1 itself does not trigger any detectable signalling effect on these cells, it
      induces an increased susceptibility to EGF (epidermal growth factor) stimulation.
      Specifically, at concentrations of EGF which promote undetectable or limited cell
      responses, the addition of sub-nanomolar concentrations of HMGB1 potentiates the
      effect of EGF by specifically activating a downstream pathway that leads to
      enhanced cell motility through an increase in Ca2+ influx, activation of
      extracellular-signal-regulated kinase 1/2 and remodelling of the actin
      cytoskeleton. These results, which identify extracellular HMGB1 as an activator
      of human tumour cell migration operating in concert with EGF, have important
      implications in the search for novel strategies to control tumour progression and
      metastatic invasion.

PMID- 15733058
TI  - Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid
      artery occlusion in mice.
AB  - Factor XI (FXI) and factor IX (FIX) are zymogens of plasma serine proteases
      required for normal hemostasis. The purpose of this work was to evaluate FXI and
      FIX as potential therapeutic targets by means of a refined ferric chloride
      (FeCl(3))-induced arterial injury model in factor-deficient mice. Various
      concentrations of FeCl(3) were used to establish the arterial thrombosis model in
      C57BL/6 mice. Carotid artery blood flow was completely blocked within 10 min in
      C57BL/6 mice by application of 3.5% FeCl(3). In contrast, FXI- and FIX-deficient
      mice were fully protected from occlusion induced by 5% FeCl(3), and were
      partially protected against the effect of 7.5% FeCl(3). The protective effect was
      comparable to very high doses of heparin (1000 units kg(-1)) and substantially
      more effective than aspirin. While FXI and FIX deficiencies were
      indistinguishable in the carotid artery injury model, there was a marked
      difference in a tail-bleeding-time assay. FXI-deficient and wild-type mice have
      similar bleeding times, while FIX deficiency was associated with severely
      prolonged bleeding times (>5.8-fold increase, P < 0.01). Given the relatively
      mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of
      FXI may be a reasonable strategy for treating or preventing thrombus formation.

PMID- 15733059
TI  - Two faces of high-molecular-weight kininogen (HK) in angiogenesis: bradykinin
      turns it on and cleaved HK (HKa) turns it off.
AB  - High-molecular-weight kininogen (HK) is a plasma protein that possesses multiple
      physiological functions. Originally identified as a precursor of bradykinin, a
      bioactive peptide that regulates many cardiovascular processes, it is now
      recognized that HK plays important roles in fibrinolysis, thrombosis, and
      inflammation. HK binds to endothelial cells where it can be cleaved by plasma
      kallikrein to release bradykinin (BK). The remaining portion of the molecule,
      cleaved HK, is designated cleaved high-molecular-weight kininogen or HKa. While
      BK has been intensively studied, the physiological implication of the generation
      of HKa is not clear. Recent studies have revealed that HKa inhibits angiogenesis
      while BK promotes angiogenesis. These findings represent novel functions of the
      kallikrein-kinin system that have not yet been fully appreciated. In this review,
      we will briefly discuss the recent progress in the studies of the molecular
      mechanisms that mediate the antiangiogenic effect of HKa and the proangiogenic
      activity of BK.

PMID- 15733060
TI  - Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in
      platelet aggregation.
AB  - The role of vitronectin (Vn) in thrombosis is currently controversial; both
      inhibitory and supportive roles have been reported. To monitor directly the
      function of Vn in thrombotic events at the site of vascular injury, we studied Vn
      deficient (Vn-/-) and wild-type (WT) control mice with two real-time intravital
      microscopy thrombosis models. In the mesenteric arteriole model, vessel injury
      was induced by ferric chloride. We observed unstable thrombi and a significantly
      greater number of emboli in Vn-/- mice. Vessel occlusion was also delayed and
      frequent vessel re-opening occurred. In the cremaster muscle arteriole model,
      vessel injury was induced by a nitrogen dye laser. We observed significantly
      fewer platelets, lower fibrin content, and unstable fibrin within the thrombi of
      Vn-/- mice. To define further the role of Vn in thrombus growth, we studied
      platelet aggregation in vitro. Consistent with our in vivo data, the second wave
      of thrombin-induced aggregation of gel-filtered platelets was abolished at a low
      concentration of thrombin in Vn-/- platelets. Interestingly, adenosine
      diphosphate (ADP)-induced platelet aggregation was significantly increased in Vn
      /- platelet-rich plasma (PRP) and this effect was attenuated by adding purified
      plasma Vn. We also observed increased platelet aggregation induced by shear
      stress in Vn-/- whole blood. These data demonstrate that Vn is a thrombus
      stabilizer. However, in contrast to released platelet granule Vn which enhances
      platelet aggregation, plasma Vn inhibits platelet aggregation.

PMID- 15733061
TI  - Predictors of the post-thrombotic syndrome during long-term treatment of proximal
      deep vein thrombosis.
AB  - BACKGROUND: The post-thrombotic syndrome is a chronic, poorly understood
      complication of deep venous thrombosis (DVT). OBJECTIVES: To evaluate predictors
      of the post-thrombotic syndrome, including intensity of long-term
      anticoagulation, and to assess the impact of the post-thrombotic syndrome on
      quality of life. PATIENTS AND METHODS: The setting was 13 Canadian hospitals and
      one US hospital. One hundred and forty-five patients with an unprovoked episode
      of proximal DVT who were initially treated with 3 months of conventional
      intensity warfarin [target International Normalized Ratio (INR) of 2.5] then
      participated in a trial comparing two intensities of long-term warfarin therapy
      (target INR 2.5 vs. INR 1.7). Post-thrombotic syndrome was assessed at the end of
      the trial using a validated clinical scale. Generic and venous disease-specific
      quality of life was compared in patients with and without the post-thrombotic
      syndrome. Multivariable regression analyses were performed to identify predictors
      of the post-thrombotic syndrome and of its severity. RESULTS: After an average
      follow-up of 2.2 years, the prevalence of post-thrombotic syndrome was 37% and of
      severe post-thrombotic syndrome was 4%. Quality of life was worse in patients
      with the post-thrombotic syndrome compared with patients who did not have it. The
      presence of factor (F)V Leiden or the prothrombin gene mutation was an
      independent predictor of both a lower risk (P = 0.006) and reduced severity (P =
      0.045) of the post-thrombotic syndrome. Intensity of anticoagulation did not
      influence the risk of developing the post-thrombotic syndrome. CONCLUSIONS: The
      post-thrombotic syndrome is a frequent and burdensome complication of proximal
      DVT, even among patients maintained on long-term oral anticoagulation. While the
      presence of FV Leiden or prothrombin gene mutation appears to be associated with
      a reduced risk of post-thrombotic syndrome, this finding requires further
      evaluation in prospective studies.

PMID- 15733062
TI  - Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate
      thrombotic responses.
AB  - Gas6 (encoded by growth arrest-specific gene 6) is a vitamin-K dependent protein
      highly homologous to coagulation protein S that is secreted from platelet alpha
      granules and has recently been demonstrated to participate in platelet thrombus
      formation. The current study evaluated the contribution of each of the three
      known Gas6 receptors (Axl, Sky and Mer) in human and mouse platelet function.
      Flow cytometry analyses confirmed that all three receptors are present on both
      human and mouse platelets. Pre-incubation of human platelets with either an anti
      Gas6 antibody or blocking antibodies to Sky or Mer inhibited platelet aggregation
      and degranulation responses to both ADP and the PAR-1 activating peptide, SFLLRN,
      by more than 80%. In contrast, a stimulatory anti-Axl antibody increased
      activation responses to these agonists, suggesting a potentiating role for Gas6
      in platelet activation. Moreover, in a mouse model of thrombosis, administration
      of Gas6 or Sky blocking antibodies resulted in a decrease in thrombus weight
      similar to clopidogrel but, unlike clopidogrel, produced no increase in template
      bleeding. Thus, Gas6 enhances platelet degranulation and aggregation responses
      through its known receptors, promoting platelet activation and mediating thrombus
      formation such that its inhibition prevents thrombosis without increasing
      bleeding.

PMID- 15733063
TI  - How to make an egg: transcriptional regulation in oocytes.
AB  - The oocyte is a highly differentiated cell. It makes organelles specialized to
      its unique functions and progresses through a series of developmental stages to
      acquire a fertilization competent phenotype. This review will integrate the
      biology of the oocyte with what is known about oocyte-specific gene regulation
      and transcription factors involved in oocyte development. We propose that
      oogenesis is reliant on a dynamic gene regulatory network that includes oocyte
      specific transcriptional regulators.

PMID- 15733064
TI  - Identification of an N-terminal transcriptional activation domain within
      Brn3b/POU4f2.
AB  - The POU-domain transcription factor Brn3b/ POU4f2 is an essential regulator of
      gene expression in mouse retinal ganglion cells. Although Brn3b's importance in
      the differentiation of these cells has been firmly established, the regions on
      Brn3b where transcriptional activation and/or repression domains reside are only
      vaguely defined, and conflicting publications report both activation and
      repression activities for Brn3b. To clarify its function, we monitored the
      transcriptional activity of Brn3b and Gal4 DNA-binding domain (DBD)-Brn3b fusion
      proteins in cotransfection experiments using either Brn3-consensus or Gal4 DNA
      binding sites to drive reporter gene expression. At Gal4 DNA-binding sites,
      transrepression activity mapping to the POU domain within Brn3b's C-terminal
      region masked any transactivation activity. More detailed experiments revealed
      that expressing abnormally high levels of POU homeodomain- or other homeodomain
      containing sequences caused fortuitous transrepression in the cotransfection
      assay. To avoid transrepression, Brn3b sequences lacking Brn3b's POU domain were
      fused to the Gal4 DBD to allow identification of regions that were responsible
      for transcriptional activation. Considerable transactivation activity was located
      between amino acid residues 100 and 239, although other regions also had
      activity. The transactivation domain synergized strongly with another
      transcription factor, LexA-VP16. At Brn3 DNA-binding sites, full-length Brn3b
      increased transcription more than 25-fold, and similar activation was observed
      with the closely related factor Brn3a/POU4f1. No transactivation activity was
      associated with the C-terminal POU domain-containing portion of Brn3b. The
      results demonstrate that Brn3b regulates gene expression through the action of a
      strong transcriptional activation domain within its N-terminal sequence.

PMID- 15733065
TI  - Optimization of the differentiation of human preadipocytes in vitro.
AB  - This study aimed at developing an optimal protocol for proliferation and
      differentiation of preadipocytes that is a prerequisite for constructing an ideal
      biohybrid composed of viable adipose precursor cells in a three-dimensional
      matrix. Such an implant could represent an adequate solution for correcting soft
      tissue defects, e.g., extensive deep burns or tumor resections. Preadipocytes
      were isolated from human subcutaneous adipose tissue samples and cultured in
      Dulbecco's modified eagle medium (DMEM)/Ham's F12 medium (F12) or OPTIMEM medium
      with or without the addition of human serum (hS) or fetal calf serum (FCS). The
      advantages of fibronectin-coated culture dishes for preadipocyte yield after
      isolation and differentiation were evaluated. After culture expansion,
      differentiation was induced by insulin, isobutylmethylxanthine, pioglitazone,
      dexamethasone, and transferrin in the absence of serum. The extent of
      differentiation was assayed by measuring the activity of glycerophosphate
      dehydrogenase as well as counting of differentiated versus undifferentiated
      cells. Our results show that fibronectin coating does not only strongly increase
      the yield of preadipocytes after isolation from adipose tissue but also
      significantly enhances differentiation of precursor cells to mature adipocytes.
      For optimal cell expansion, DMEM/F12 is more promoting than OPTIMEM and culturing
      with FCS shows a slightly better proliferation compared with hS supplementation.
      Differentiation, in contrast, is significantly improved when hS is used instead
      of FCS during proliferation. Our results smooth the way for autologous
      preadipocyte culturing and show that hS for preadipocyte culturing opens new and
      promising perspectives for adipose tissue engineering by optimizing in vitro
      expansion in cell culture and inducing substantial differentiation.

PMID- 15733066
TI  - Expression of human TFF3 in relation to growth of HT-29 cell subpopulations:
      involvement of PI3-K but not STAT6.
AB  - The trefoil factor family (TFF) peptides 1 and 2 (TFF1 and 2) are expressed in
      mucus cells of the stomach, whereas TFF3 is localized in goblet cells of the
      intestine. In the present study, we aimed to determine whether
      phosphatidylinositol 3-kinase (PI3-K) or signal transducer and activator of
      transcription protein 6 (STAT6) is involved in the expression of goblet cell
      specific markers. TFF3 expression was analyzed by RT-PCR, Northern blot, and
      radioimmunoassay (RIA) in relation to cell growth in subclones of HT-29 cells
      including the CL.16E and methotrexate (MTX) cell lines, which both exhibit a
      phenotype of mucus-secreting intestinal cells. A 30-fold increase in TFF3 mRNA
      levels and a 10-fold increase in TFF3-cell content were observed between the
      early proliferative and the late confluency states. The levels of MUC2 and MUC3
      mRNA were also increased in the course of the differentiation process. A three to
      fourfold increase in PI3-K and Akt activities was observed in early post
      confluent cells as compared with pre-confluent cells. Exposure of pre- and post
      confluent cells to LY294002, a specific PI3-K inhibitor, for 1-4 days profoundly
      reduced TFF3 and MUC2 expression. A marked reduction in mucin granules content
      was also observed in LY-treated cells. Inhibition of the mitogen-activated
      protein (MAP) kinase kinase (MEK) with PD98059 did not modify the course of
      differentiation of the goblet cell lines. Moreover, stable transfection of HT-29
      CL.16E cells with a dominant negative form of STAT6 had no effect on TFF3
      induction. Together, these data indicate that PI3-K promotes the expression of
      TFF3 and MUC2 and that the PI3-K/Akt pathway may play a pivotal role in
      intestinal goblet cell differentiation.

PMID- 15733067
TI  - Laminin-1 and epidermal growth factor family members co-stimulate fetal pancreas
      cell proliferation and colony formation.
AB  - The epidermal growth factor (EGF) family is implicated in the development and
      function of multiple cells and organs, including the pancreas. We used a serum
      free, low-cell density culture system to investigate the effect of EGFs on fetal
      pancreas cells. By RT-PCR, the EGF receptors ErbB 1-3 were detected in the
      developing mouse pancreas between embryonic day (E) 13.5 and E17.5, whereas ErbB4
      was not detected until E17.5. The presence but not absence of the basement
      membrane glycoprotein laminin-1, betacellulin, and to a lesser extent EGF,
      transforming growth factor alpha, heparin binding EGF, and epiregulin induced
      E15.5 pancreatic cells to proliferate and form cystoid and solid colonies. These
      results demonstrate that laminin-1 and EGF signaling pathways interact to promote
      pancreas development.

PMID- 15733068
TI  - Evidence that the Dictyostelium STAT protein Dd-STATa plays a role in the
      differentiation of inner basal disc cells and identification of a promoter
      element essential for expression in these cells.
AB  - Dd-STATa, a Dictyostelium homolog of the metazoan STAT (signal transducers and
      activators of transcription) proteins, is necessary in the slug for correct entry
      into culmination. Dd-STATa-null mutant fails to culminate and its phenotype
      correlates with the loss of a funnel-shaped core region, the pstAB core region,
      which expresses both the ecmA and ecmB genes. To understand how the
      differentiation of pstAB core cells is regulated, we identified an EST that is
      expressed in the core cells of normal slugs but down-regulated in the Dd-STATa
      null mutant. This EST, SSK348, encodes a close homolog of the Dictyostelium
      acetyl-CoA synthetase (ACS). A promoter fragment of the cognate gene, aslA
      (acetyl-CoA synthetase-like A), was fused to a lacZ reporter and the expression
      pattern determined. As expected from the behavior of the endogenous aslA gene,
      the aslA::lacZ fusion gene is not expressed in Dd-STATa-null slugs. In parental
      cells, the aslA promoter is first activated in the funnel-shaped core cells
      located at the slug anterior, the "pstAB core." During culmination, the pstAB
      core cells move down, through the prespore cells, to form the inner part of the
      basal disc. As the spore mass climbs the stalk, the aslA gene comes to be
      expressed in cells of the upper and lower cups, structures that cradle the spore
      head. Deletion and point mutation analyses of the promoter identified an AT-rich
      sequence that is necessary for expression in the pstAB core. This acts in
      combination with repressor regions that prevent ectopic aslA expression in the
      pre-stalk regions of slugs and the stalks of culminants. Thus, this study
      confirms that Dd-STATa is necessary for the differentiation of pstAB core cells,
      by showing that it is needed for the activation of the aslA gene. It also
      identifies aslA promoter elements that are likely to be regulated, directly or
      indirectly, by Dd-STATa.

PMID- 15733069
TI  - Molecular mechanisms activating muscle protein degradation in chronic kidney
      disease and other catabolic conditions.
AB  - Muscle atrophy is a prominent feature of chronic kidney disease (CKD) and is
      frequent in other catabolic conditions. Results from animal models of these
      conditions as well as patients indicate that atrophy is mainly owing to
      accelerated muscle proteolysis in the ubiquitin-proteasome (Ub-P'some)
      proteolytic system. The Ub-P'some system, however, rapidly degrades actin or
      myosin but cannot breakdown actomyosin or myofibrils. Consequently, another
      protease must initially cleave the complex structure of muscle. We identified
      caspase-3 as an initial and potentially rate-limiting proteolytic step that
      cleaves actomyosin/myofibrils to produce substrates degraded by the Ub-P'some
      system. In rodent models of CKD and other catabolic conditions, we find that
      caspase-3 is activated and cleaves actomyosin to actin, myosin and their
      fragments. This initial proteolytic step in muscle leaves a characteristic
      footprint, a 14-kDa actin band, providing a potential diagnostic tool to detect
      muscle catabolism. We also found that stimulation of caspase-3 activity depends
      on inhibition of IRS-1-associated phosphatidylinositol 3-kinase (PI3K) activity;
      inhibiting PI3K in muscle cells also leads to expression of a critical E3
      ubiquitin-conjugating enzyme involved in muscle protein breakdown: atrogin
      1/MAFbx. Thus, protein breakdown by caspase-3 and the ubiquitin-proteasome system
      in muscle are stimulated by the same signal: a low PI3K activity. These responses
      could yield therapeutic strategies to block muscle atrophy.

PMID- 15733070
TI  - High-dose glucose-insulin-potassium treatment reduces myocardial apoptosis in
      patients with acute myocardial infarction.
AB  - BACKGROUND: Several clinical trials have suggested that a metabolic cocktail of
      glucose-insulin-potassium (GIK) decreases mortality rates in patients with acute
      myocardial infarction (AMI). It has also been reported that Fas-mediated
      apoptosis plays an important role in ischaemic/reperfusion injury in the rat
      model. This study was designed to evaluate the interaction of
      ischaemic/reperfusion and reperfusion therapy coadministered with high-dose GIK
      treatment on soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) plasma concentration
      in patients with AMI. MATERIALS AND METHODS: Seventy-four patients presenting
      with AMI who underwent reperfusion therapy were randomized into a GIK group (n =
      35) receiving high-dose GIK for 24 h or a vehicle group (n = 39). Thirty-four
      control subjects were also enrolled in the present study. Strepavidin-biotin
      ELISA was used to determine the soluble sFas and sFasL plasma concentration at
      baseline, 24 h (h), 3 day (d), 7 d and 14 d. RESULTS: Soluble Fas and sFas-L
      serum concentrations ([sFas] and [sFas-L]) of patients with AMI were
      significantly elevated at baseline as compared with normal controls (NCs; P <
      0.01 vs. NC). The sFas in the GIK and vehicle groups markedly decreased 24 h
      after the GIK infusion (10.7-->5.9 ng mL(-1) and 9.7-->6.5 ng mL(-1); P < 0.01
      vs. baseline) and then increased during the 3-7-d period (5.9-->12.1 ng mL(-1)
      and 6.5-->11.1 ng mL(-1); P < 0.01 vs. 24 h). The GIK group demonstrated reduced
      sFas (12.1-->5.9 ng mL(-1)) at 14 d (P < 0.01 vs. 7 d), with no concomitant
      changes in the vehicle group. The sFas-L in the GIK and vehicle groups was not
      significant different during the 14-d period. CONCLUSIONS: These results indicate
      that the sFas and sFasL in patients with AMI increased significantly compared
      with NC. Owing to the cardioprotective effects reported here and by others, a
      high-dose GIK infusion co-administered with the timely re-establishment of
      nutritive perfusion should be strongly considered as a treatment of choice for
      AMI. Additionally, sFas may be a valuable marker of the physiological response to
      ischaemic/reperfusion injury and reperfusion associated with high-dose GIK
      treatment.

PMID- 15733071
TI  - Postprandial changes in LDL phenotypes in patients with myocardial infarction.
AB  - BACKGROUND: Low-density lipoprotein (LDL) particle size is strongly affected by
      both fasting and postprandial triglyceride levels. We report here that the LDL
      phenotype shifts toward the smaller phenotype during oral fat tolerance tests
      (OFTTs) in some patients with myocardial infarction (MI); a condition closely
      associated with postprandial increases of triglyceride and remnant-like particles
      (RLPs). METHODS: Oral fat tolerance tests were performed on 63 MI patients with
      fasting serum triglyceride levels of less than 2.25 mmol L-1 (= 200 mg dL-1).
      Remnant-like particles and other serum lipids were compared among patients
      characterized by three LDL phenotypes based on nondenaturing gradient gel
      electrophoresis: pattern A (large LDLs, peak LDL particle size > or = 260 A),
      pattern I (intermediate-sized LDLs, LDL size > 255 A, < 260 A), and pattern B
      (small, dense LDLs, LDL size < or = 255 A). RESULTS: The LDL size decreased
      significantly in patients with the highest tertile of areas under the incremental
      curves (AUICs) of triglycerides above the fasting levels. The LDL phenotype
      shifted toward the smaller phenotype after a fat load in three of eight patients
      with pattern A and in seven of 35 patients with pattern I. The AUICs of
      triglyceride-rich lipoproteins were significantly higher in these patients than
      in the patients exhibiting little change in LDL size, whereas the fasting
      metabolic parameters were similar among the patients of the same LDL phenotype in
      the fasting state. CONCLUSION: These results suggest that alimentary lipaemia
      plays an important role in the remodeling of LDL particles into the more
      atherogenic small, dense LDLs in patients with MI.

PMID- 15733072
TI  - Quantification of dose perturbation by plaque in vascular brachytherapy.
AB  - BACKGROUND: Dose prescription and reporting in vascular brachytherapy (VBT) is
      based on the assumption that the vessel wall is water equivalent, which does not
      consider a possible dose perturbation by plaque. As the extent of this
      perturbation is unknown, we aimed to quantify dose attenuation by atherosclerotic
      plaque for beta- and gamma-radiation. MATERIAL AND METHODS: The dose delivered
      from Strontium-90/Yttrium-90 ((90)Sr/Y) and Iridium-192 ((192)Ir) sources with
      and without human peripheral arteries ((90)Sr/Y: n = 38, (192)Ir: n = 7)
      surrounding the respective delivery catheter was determined with radiochromic
      films. Plaque and vessel wall thickness were measured using light microscopy.
      From the ratio-attenuated doseunattenuated dose (dose perturbation factor: DPF)
      we determined averaged attenuation coefficients for atherosclerotic plaque
      (micro(P)) and the residual part of the vessel wall (micro(W)) by regression
      analysis based on the function DPF = exp(-micro(P) * plaque thickness -micro(W) *
      residual wall thickness). RESULTS: Attenuation in case of (192)Ir was less than
      the measurement uncertainties. For beta-radiation correlation was found by
      discrimination between calcified and noncalcified plaque. Classifying
      noncalcified plaque as normal arterial tissue, the regression coefficient was r =
      0.845 at micro(P)= 0.5356 mm(-1) and micro(W) = 0.0663 mm(-1). CONCLUSIONS:
      Vascular brachytherapy with beta radiation in calcified arteries results in
      significant dose attenuation within the vessel wall, which can be calculated on
      knowing the vascular morphometry. Thus, plaque thickness should be taken into
      account in treatment planning and retrospective analyses.

PMID- 15733073
TI  - Facilitated nitration and oxidation of LDL in cigarette smokers.
AB  - BACKGROUND: Cigarette smoking increases the risk of developing atherosclerosis
      and ischaemic heart disease. Smoking-induced oxidative stress is considered to
      favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the
      atherogenic process. We investigated whether peroxynitrite, a reaction product of
      cigarette smoke, is involved in facilitated oxidation of LDL in smokers.
      MATERIALS AND METHODS: Plasma LDL was obtained from 10 healthy asymptomatic
      cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative
      stress in the plasma was assessed by LDL subfraction assay using anion-exchange
      high-performance liquid chromatography (AE-HPLC) and measurements of
      thiobarbituric acid-reactive substances (TBARS), 8-hydroxydeoxyguanosine (8
      OHdG), vitamin E, 3-nitrotyrosine and 3-chlorotyrosine. RESULTS: Smokers showed a
      significantly higher level of TBARS and 8-OHdG as well as a significantly lower
      level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more.
      The LDL subfraction assay demonstrated an increase in oxidatively modified LDL,
      as expressed by lower levels of LDL1 and higher levels of LDL2. The 3
      nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in
      smokers than nonsmokers, while the 3-chlorotyrosine levels remained unchanged. In
      addition, these changes observed in the smokers were further accelerated within
      30 min after resumption of cigarette smoking when compared with the levels before
      smoking resumption. CONCLUSION: The present study suggests that peroxynitrite
      plays a significant role in oxidative modification of plasma LDL induced by
      cigarette smoking.

PMID- 15733074
TI  - Tissue-specific regulation of lipoprotein lipase in humans: effects of fasting.
AB  - BACKGROUND: We have previously reported that the activity of lipoprotein lipase
      (LPL) measured in postheparin plasma from humans fasted for 30 h is increased
      relative to the fed state. This is in contrast to laboratory animals, where the
      strong down-regulation of LPL in their adipose tissue on fasting is reflected in
      decreased levels of LPL activity in postheparin plasma. MATERIALS AND METHODS: To
      search for the tissue source of the increase in LPL activity on fasting of
      humans, young, healthy subjects were fasted for 10, 20 or 30 h, and LPL was
      measured in plasma (pre- and postheparin) and in biopsies from subcutaneous
      adipose tissue (abdominal) and from a skeletal muscle (tibialis anterior). Both
      LPL activity and LPL protein mass were measured in the tissue homogenates. Values
      after fasting were compared with values from postprandial samples obtained 2 h
      after a meal. RESULTS: Fasting for up to 30 h did not alter LPL activity in basal
      plasma (preheparin). LPL activity in postheparin plasma remained unchanged after
      10 and 20 h of fasting, but was increased by 50% after 30 h (P < 0.05). Ten hours
      of fasting caused a 25% (P < 0.05) decrease in LPL activity in subcutaneous
      adipose tissue, while LPL activity in skeletal muscle remained unchanged. After
      30 h of fasting, both LPL activity and mass had decreased by approximately 50% (P
      < 0.05) in adipose tissue, but had increased by approximately 100% (P < 0.05) in
      muscle. CONCLUSIONS: The increase in postheparin plasma LPL activity after 30 h
      of total food deprivation of healthy human subjects seemed to reflect an
      increased activity and mass of LPL in skeletal muscle.

PMID- 15733075
TI  - Retinoic acid increases tissue and plasma contents of nerve growth factor and
      prevents neuropathy in diabetic mice.
AB  - BACKGROUND: Decreased production of nerve growth factor (NGF) may contribute to
      diabetic neuropathy; however, exogenous administration of NGF induces only a
      modest benefit. Retinoic acid (RA) promotes the endogenous expression of nerve
      growth factor and its receptor. We studied the effects of RA on diabetic
      neuropathy in mice with streptozotocin-induced diabetes. MATERIAL AND METHODS:
      One hundred and twenty National Institutes of Health (NIH) albino mice randomly
      separated into three groups (A, n = 30; B, n = 30; C, n = 60). Diabetes mellitus
      was induced with streptozotocin in groups A and B. Animals from group A received
      a subcutaneous injection of 25 microl of mineral oil daily for 90 days, while
      those from group B received a subcutaneous injection of 20 mg kg(-1) of all trans
      RA. Animals from group C were taken as controls. At the end of the experiment,
      blood glucose and NGF levels (both in serum and sciatic nerve) were measured. Two
      behavioural tests were conducted in a blind fashion to detect abnormalities of
      thermal and nociceptive thresholds. RESULTS: Contents of NGF in healthy untreated
      mice were 1490 +/- 190 pg mg(-1) in nerve and 113 +/- 67 pg mg(-1) in serum; in
      diabetic untreated mice the values were 697 +/- 219 pg mL(-1) in nerve and 55 +/-
      41 pg mL(-1) in serum; and in diabetic mice treated with RA the values were 2432
      +/- 80 pg mL(-1) in nerve and 235 +/- 133 pg mg(-1) in serum (P < 0.002).
      Ultrastructural evidence of nerve regeneration and sensitivity tests improved in
      diabetic mice treated with RA as compared with nontreated diabetic mice.
      CONCLUSION: Our findings indicate that administration of RA increases serum and
      nerve contents of NGF in diabetic mice and suggest a potential therapeutic role
      for retinoic acid in diabetic patients.

PMID- 15733076
TI  - Circulating ADMA concentrations are elevated in hypopituitary adults with and
      without growth hormone deficiency.
AB  - BACKGROUND: Cardiovascular mortality is increased in patients with
      hypopituitarism. Elevated concentrations of the endogenous NO synthase antagonist
      asymmetrical dimethylarginine (ADMA) may be related to the development of
      atherosclerosis and are associated with cardiovascular risk. We studied the
      concentrations of ADMA in hypopituitary patients with and without growth hormone
      deficiency (GHD) and in healthy subjects. MATERIALS AND METHODS: Plasma from 44
      patients with hypopituitarism with (n = 30) and without GHD (n = 14) and from 25
      age- and sex-matched healthy controls was taken for analysis of L-arginine, ADMA,
      symmetrical dimethylarginine (SDMA) and clinical parameters. Further plasma from
      10 hypopituitary patients was examined before and after treatment with 9 g of
      oral L-arginine for 14 days. RESULTS: Asymmetrical dimethylarginine was
      significantly higher in the hypopituitary patients than in the controls (0.63 +/-
      0.12 vs. 0.51 +/- 0.15 micromol L(-1); P < 0.005). L-arginine and the L
      arginine/ADMA ratios were lower in the subjects with hypopituitarism (53 +/- 18
      vs. 90 +/- 29 micromol L(-1) and 87 +/- 31 vs. 185 +/- 59; both P < 0.0001).
      Symmetrical dimethylarginine was comparable between the patients and the
      controls. L-arginine and dimethylarginines were associated with 2-h stimulated
      glucose levels in a glucose tolerance test (r = 0.33; P < 0.05), but not other
      cardiovascular risk factors. Oral L-arginine supplementation normalized the
      reduced L-arginine/ADMA ratio in the hypopituitary patients. CONCLUSION:
      Asymmetrical dimethylarginine is elevated in patients with hypopituitarism
      independent of GHD and traditional risk factors. This might contribute to the
      increased cardiovascular morbidity in hypopituitary patients.

PMID- 15733077
TI  - Eradication of Helicobacter pylori increases platelet count in patients with
      idiopathic thrombocytopenic purpura in Japan.
AB  - BACKGROUND: The effect of Helicobacter pylori eradication on the platelet count
      in patients with thrombocytopenic purpura is controversial. In this multicentre
      study, we prospectively assessed the effect of H. pylori eradication therapy in
      idiopathic thrombocytopenic purpura patients. MATERIALS AND METHODS: Thirty-five
      consecutive patients with chronic idiopathic thrombocytopenic purpura (11 males
      and 24 females, a median age of 57) were assessed for H. pylori infection by use
      of a urea breath test. All patients received 1-week triple therapy (amoxicillin,
      clarithromycin, and lansoprazole) to eradicate H. pylori. At 6 months, idiopathic
      thrombocytopenic purpura patients with a platelet count recovery of greater than
      100 x 10(9) L(-1) were defined as idiopathic thrombocytopenic purpura responders.
      RESULTS: Helicobacter pylori infection was observed in 25 (71%) of the 35
      patients. All infected patients were cured. Eleven patients were identified as
      idiopathic thrombocytopenic purpura responders; 24 were considered nonresponders.
      Platelet counts improved by more than 100 x 10(9) L(-1) in 11 (44%) of the 25
      patients cured of H. pylori infection, while none of the 10 patients H. pylori
      negative patients experienced the same improvement (P = 0.015). Univariate
      analysis showed that H. pylori infection and its eradication were significant
      factors associated with platelet recovery (P = 0.015). CONCLUSIONS: Helicobacter
      pylori infection played a role in the pathogenesis of idiopathic thrombocytopenic
      purpura in approximately 30% of all patients assessed and 45% of the patients
      with H. pylori infection. Eradication of H. pylori in idiopathic thrombocytopenic
      purpura patients led to improved disease activity.

PMID- 15733078
TI  - Improvement of portal hypertension and hepatic blood flow in cirrhotic rats by
      oestrogen.
AB  - BACKGROUND: In this study, we investigated the effects of oestrogen on nitric
      oxide synthase activity and nitric oxide production using the cirrhotic rat
      liver. MATERIAL AND METHODS: Cirrhosis was induced by dimethylnitrosamine.
      Estradiol valerate was subcutaneously injected twice at week 4 after
      dimethylnitrosamine treatment. Furthermore, subcutaneous injection of an
      oestrogen receptor antagonist, ICI-182.780, was performed 2 days before
      administration of estradiol valerate. Portal pressure and hepatic blood flow were
      measured. Nitric oxide synthase activity was assessed by l-citrulline generation.
      Sinusoidal endothelial cells were isolated from the cirrhotic rat liver and
      cultured. The cells were incubated with estradiol and/or ICI-182.780 for 24 h.
      Images for nitric oxide in sinusoidal endothelial cells were obtained using
      diaminofluorescein-2 diacetate. RESULTS: Cirrhotic rats treated with estradiol
      valerate showed a significant decrease in portal pressure and a significant
      increase in hepatic blood flow compared with those of control cirrhosis rats.
      However, in cirrhotic rats treated with ICI-182.780, the reduction of portal
      pressure and elevation of hepatic blood flow were completely inhibited. In
      cirrhotic rats treated with estradiol valerate, nitric oxide synthase activity
      was increased compared with that in control cirrhotic rats. The fluorescent level
      of intracellular nitric oxide in estradiol-stimulated, cultured, sinusoidal
      endothelial cells was higher than that in nontreated sinusoidal endothelial
      cells. CONCLUSIONS: The present study indicated that oestrogen plays an important
      role in the enhancement of nitric oxide production in sinusoidal endothelial
      cells of cirrhotic liver and reduces the portal pressure in cirrhotic rats.

PMID- 15733079
TI  - Visualization of local Ca2+ dynamics with genetically encoded bioluminescent
      reporters.
AB  - Measurements of local Ca2+ signalling at different developmental stages and/or in
      specific cell types is important for understanding aspects of brain functioning.
      The use of light excitation in fluorescence imaging can cause phototoxicity,
      photobleaching and auto-fluorescence. In contrast, bioluminescence does not
      require the input of radiative energy and can therefore be measured over long
      periods, with very high temporal resolution. Aequorin is a genetically encoded
      Ca(2+)-sensitive bioluminescent protein, however, its low quantum yield prevents
      dynamic measurements of Ca2+ responses in single cells. To overcome this
      limitation, we recently reported the bi-functional Ca2+ reporter gene, GFP
      aequorin (GA), which was developed specifically to improve the light output and
      stability of aequorin chimeras [V. Baubet, et al., (2000) PNAS, 97, 7260-7265].
      In the current study, we have genetically targeted GA to different microdomains
      important in synaptic transmission, including to the mitochondrial matrix,
      endoplasmic reticulum, synaptic vesicles and to the postsynaptic density. We
      demonstrate that these reporters enable 'real-time' measurements of subcellular
      Ca2+ changes in single mammalian neurons using bioluminescence. The high signal
      to-noise ratio of these reporters is also important in that it affords the
      visualization of Ca2+ dynamics in cell-cell communication in neuronal cultures
      and tissue slices. Further, we demonstrate the utility of this approach in ex
      vivo preparations of mammalian retina, a paradigm in which external light input
      should be controlled. This represents a novel molecular imaging approach for non
      invasive monitoring of local Ca2+ dynamics and cellular communication in tissue
      or whole animal studies.

PMID- 15733080
TI  - A role for synGAP in regulating neuronal apoptosis.
AB  - The brain-specific Ras/Rap GTPase-activating protein synGAP is a major component
      of the postsynaptic density at glutamatergic synapses. It is a target for
      phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II, which up
      regulates its GTPase-activating activity. Thus, SynGAP may play an important role
      in coupling N-methyl-D-aspartate-type glutamate receptor activation to signaling
      pathways downstream of Ras or Rap. Homozygous deletion of synGAP is lethal within
      the first few days after birth. Therefore, to study the functions of synGAP, we
      used the cre/loxP recombination system to produce conditional mice mutants in
      which gradual loss of synGAP begins at approximately 1 week, and usually becomes
      maximal by 3 weeks, after birth. The resulting phenotypes fall into two groups.
      In a small group, the level of synGAP protein is reduced to 20-25% of wild type,
      and they die at 2-3 weeks of age. In a larger group, the levels remain higher
      than approximately 40% of wild type, and they survive and remain healthy. In all
      mutants, however, an abnormally high number of neurons in the hippocampus and
      cortex undergo apoptosis, as detected by caspase-3 activation. The effect is cell
      autonomous, occurring only in neuronal types in which the synGAP gene is
      eliminated. The level of caspase-3 activation in neurons correlates inversely
      with the level of synGAP protein measured at 2 and 8 weeks after birth,
      indicating that neuronal apoptosis is enhanced by reduction of synGAP. These data
      show that synGAP plays a role in regulation of the onset of apoptotic neuronal
      death.

PMID- 15733081
TI  - The removal of extracellular calcium: a novel mechanism underlying the
      recruitment of N-methyl-D-aspartate (NMDA) receptors in neurotoxicity.
AB  - The involvement of NMDA-type glutamate receptor in neuronal injury established in
      experimental stroke and neurotrauma models has been recently challenged by
      failures in treatment of stroke/neurotrauma patients with NMDA receptor
      antagonists. NMDA receptor activity is known to be essential for mediating a
      multitude of physiological functions. However, how NMDA receptors are recruited
      to cause neuronal injury remains unclear. Here we report that the time period
      during which initial NMDA receptor up-regulation occurs is critical for the
      recruitment of NMDA receptors causing neuronal injury during extracellular
      calcium (Ca2+) reperfusion in cultured hippocampal neurons, and represents the
      key period for neuronal protection by NMDA receptor antagonists. Furthermore, we
      identified that via intracellular sodium (Na+), extracellular Ca2+ depletion
      induces the up-regulation of NMDA receptor gating. Taken together, our study
      provides direct experimental evidence suggesting that determination of when and
      how NMDA receptors are recruited to cause neurotoxicity is essential for guiding
      treatment via antagonism of NMDA receptor functions.

PMID- 15733082
TI  - A novel thiol antioxidant that crosses the blood brain barrier protects
      dopaminergic neurons in experimental models of Parkinson's disease.
AB  - It is believed that oxidative stress (OS) plays an important role in the loss of
      dopaminergic nigrostriatal neurons in Parkinson's disease (PD) and that treatment
      with antioxidants might be neuroprotective. However, most currently available
      antioxidants cannot readily penetrate the blood brain barrier after systemic
      administration. We now report that AD4, the novel low molecular weight thiol
      antioxidant and the N-acytel cysteine (NAC) related compound, is capable of
      penetrating the brain and protects neurons in general and especially dopaminergic
      cells against various OS-generating neurotoxins in tissue cultures. Moreover, we
      found that treatment with AD4 markedly decreased the damage of dopaminergic
      neurons in three experimental models of PD. AD4 suppressed amphetamine-induced
      rotational behaviour in rats with unilateral 6-OHDA-induced nigral lesion. It
      attenuated the reduction in striatal dopamine levels in mice treated with 1
      methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP). It also reduced the
      dopaminergic neuronal loss following chronic intrajugular administration of
      rotenone in rats. Our findings suggest that AD4 is a novel potential new
      neuroprotective drug that might be effective at slowing down nigral neuronal
      degeneration and illness progression in patients with PD.

PMID- 15733084
TI  - Novel transcription factor Satb2 interacts with matrix attachment region DNA
      elements in a tissue-specific manner and demonstrates cell-type-dependent
      expression in the developing mouse CNS.
AB  - Satb1 is a first cell-type-specific transcription factor of a novel type that
      functions as a regulator of the transcription of large chromatin domains. We
      identified a close homologue of Satb1, Satb2, in a cDNA subtraction screening in
      a search for genes controlling neural differentiation. Satb2 showed 61% amino
      acid homology to Satb1. Satb2 and Satb1 expression was detected in different cell
      subpopulations of developing mouse CNS in a mutually exclusive manner. In the
      electrophoretic mobility shift assay we demonstrate that nuclear extracts from
      the embryonic day 18.5 mouse developing neocortex, in contrast to basal ganglia,
      contain a protein complex interacting with matrix attachment region DNA elements
      (MARs) with high affinity. Endogenous Satb2 protein is a part of this complex. In
      the developing neocortex Satb2 was detected largely in the superficial layers. In
      the developing spinal cord Satb2 expression marks a subpopulation of Lbx1
      positive neurons dorsally and a subgroup of Isl1-positive neurons ventrally. In
      the Lbx1 mutants Satb2 expression is greatly reduced. We suggest that Satb2 may
      regulate differentiation of subsets of neurons at the level of higher order
      chromatin structure via binding to MARs.

PMID- 15733083
TI  - Zinc accumulation after target loss: an early event in retrograde degeneration of
      thalamic neurons.
AB  - Accumulation of cytoplasmic zinc is linked with a cascade of events leading to
      neuronal death. In many in vivo models of zinc-induced cell death, toxic
      concentrations of synaptically released zinc enter vulnerable neurons via
      neurotransmitter- or voltage-gated ion channels. In vitro studies demonstrate, in
      addition, that zinc can be liberated from intracellular stores following
      oxidative stress and contribute to cell death processes, including apoptosis.
      Here we describe accumulation of intracellular zinc in an in vivo model of cell
      death in the absence of presynaptic zinc release. We focused on the lateral
      geniculate nucleus (LGN) because LGN neurons undergo apoptosis when separated
      from their target, the primary visual cortex (V1), and the LGN is mostly devoid
      of zinc-containing presynaptic terminals. Infant and adult rats and adult mice
      received unilateral ablation of V1, either by aspiration or kainate injection.
      One to 14 days later, brain sections were stained with selenium autometallography
      or fluorescently labeled to localize zinc, or stained immunochemically for
      activated caspase-3. V1 lesions led to zinc accumulation in LGN neurons in infant
      and adult subjects. Zinc-containing neurons were evident 1-3 days after
      aspiration lesions, depending on age, but not until 14 days after kainate
      injection. Zinc accumulation was followed rapidly by immunostaining for activated
      caspase-3. Our data indicate that like neurotrauma and excitotoxicity, target
      deprivation leads to accumulation of zinc in apoptotic neurons. Moreover, zinc
      accumulation in vivo can occur in the absence of presynaptic zinc release.
      Together these findings suggest that accumulation of intracellular zinc is a
      ubiquitous component of the cell death cascade in neurons.

PMID- 15733085
TI  - Modulation of glycine receptor subunits and gephyrin expression in the rat facial
      nucleus after axotomy.
AB  - In the last decade, numerous studies have investigated molecular changes in
      excitatory glutamatergic receptors in axotomized motoneurons, but few data are
      available concerning the modulation of inhibitory amino acid receptors. We report
      here the effect of axotomy on the expression of glycine receptors, gephyrin,
      vesicular inhibitory amino acid transporter (VIAAT) and synapsin I in rat facial
      motor neurons as demonstrated by in situ hybridization and immunohistochemistry.
      The facial nerve trunk was sectioned unilaterally and rats were killed 1, 3, 8,
      30 or 60 days after surgery. We investigated the mechanisms underlying the
      changes in production of these proteins following axotomy by perfusing the facial
      nerve with colchicine or tetrodotoxin, and injecting cardiotoxin or botulinum
      toxin independently and unilaterally into the whisker pads of normal rats.
      Animals were killed 8 days later and processed for immunohistochemistry. The
      abundance of GlyR subunits and gephyrin fell sharply in the axotomized facial
      nucleus. This decrease began 1 day after axotomy and was lowest at 8 days, with
      protein levels returning to normal by day 60. Abnormal synapsin immunolabelling
      was also observed between days 8 and 60 after axotomy but we detected no change
      in VIAAT immunoreactivity. The effect of colchicine was similar to, but weaker
      than, that of axotomy. In contrast, tetrodotoxin, cardiotoxin and botulinum toxin
      had no significant effect. Thus, axotomy-induced changes probably resulted from a
      loss of trophic factor transported from the periphery or a positive injury
      signal, or both. They did not seem to depend on the disruption of activity.

PMID- 15733086
TI  - A TASK-like pH- and amine-sensitive 'leak' K+ conductance regulates neonatal rat
      facial motoneuron excitability in vitro.
AB  - A 'leak' potassium (K+) conductance (gK(Leak)) modulated by amine
      neurotransmitters is a major determinant of neonatal rat facial motoneuron
      excitability. Although the molecular identity of gK(Leak) is unknown, TASK-1 and
      TASK-3 channel mRNA is found in facial motoneurons. External pH, across the
      physiological range (pH 6-8), and noradrenaline (NA) modulated a conductance that
      displayed a relatively linear current/voltage relationship and reversed at the K+
      equilibrium potential, consistent with inhibition of gK(Leak). The pH-sensitive
      current (I(pH)), was maximal around pH 8, fully inhibited near pH 6 and was
      described by a modified Hill equation with a pK of 7.1. The NA-induced current
      (I(NA)) was occluded at pH 6 and enhanced at pH 7.7. The TASK-1 selective
      inhibitor anandamide (10 microM), its stable analogue methanandamide (10 microM),
      the TASK-3 selective inhibitor ruthenium red (10 microM) and Zn2+ (100-300
      microM) all failed to alter facial motoneuron membrane current or block I(NA) or
      I(pH). Isoflurane, a volatile anaesthetic that enhances heteromeric TASK-1/TASK-3
      currents, increased gK(Leak). Ba2+, Cs+ and Rb+ blocked I(NA) and I(pH) voltage
      dependently with maximal block at hyperpolarized potentials. 4-Aminopyridine (4
      AP, 4 mM) voltage-independently blocked I(NA) and I(pH). In summary, gK(Leak)
      displays some of the properties of a TASK-like conductance. The linearity of
      gK(Leak) and an independence of activation on external [K+] suggests against pH
      sensitive inwardly rectifying K+ channels. Our results argue against principal
      contributions to gK(Leak) by homomeric TASK-1 or TASK-3 channels, while the
      potentiation by isoflurane supports a predominant role for heterodimeric TASK
      1/TASK-3 channels.

PMID- 15733087
TI  - Functional characterization of rat rho2 subunits expressed in HEK 293 cells.
AB  - GABA(C) receptors are thought to be homo- or heteropentamers composed of rho1,
      rho2 and rho3 subunits. Previous work on rat rho2 subunits expressed in Xenopus
      oocytes has suggested that they do not form functional homo-oligomeric GABA(C)
      receptors, but do combine with rho1 or rho3 subunits to form hetero-oligomers.
      These findings are difficult to interpret because both human and mouse rho2
      subunits do form functional homo-oligomeric receptors. Also, many regions of the
      rat brain express solely rho2 subunit transcripts which, according to presently
      available evidence, would not result in expression of functional GABA(C)
      receptors. We show here that homomeric rat rho2 receptors can be expressed in HEK
      293 cells. Homo-oligomeric rat rho2 receptors expressed in mammalian cells
      matured slowly and displayed small but detectable GABA-induced currents with slow
      kinetics. Rat rho2 receptors also had a decreased sensitivity to picrotoxin and a
      marked sensitivity to the GABA(C) receptor agonist cis-aminocrotonic acid. Our
      results demonstrate for the first time the expression of functional homomeric rat
      rho2 receptors, and suggest that rho(2) subunits may contribute to brain
      function, including in areas not expressing other rho subunits.

PMID- 15733088
TI  - Complex effects of stromal cell-derived factor-1 alpha on melanin-concentrating
      hormone neuron excitability.
AB  - Stromal cell-derived factor 1alpha (SDF-1alpha), a chemoattractant for leucocytes
      and neurons, and its receptor, CXCR4 are expressed in subsets of neurons of
      specific brain areas. In rat lateral hypothalamic area (LHA) we show, using
      immunocytochemistry, that CXCR4 is localized within melanin-concentrating hormone
      (MCH)-expressing neurons, mainly involved in feeding behaviour regulation. We
      investigated whether SDF-1alpha may control MCH neuronal activity. Patch-clamp
      recordings in rat LHA slices revealed multiple effects of SDF-1alpha on the
      membrane potential of MCH neurons, indirect through glutamate/GABA release and
      direct through GIRK current activation. Moreover, SDF-1alpha at 0.1-1 nM
      decreased peak and discharge frequency of action potential evoked by current
      pulses. These effects were further confirmed in voltage-clamp experiments, SDF
      1alpha depressing both potassium and sodium currents. At 10 nM, however, SDF
      1alpha increased peak and discharge frequency of action potential evoked by
      current pulses. Using a specific CXCR4 antagonist, we demonstrated that only the
      depressing effect on AP discharge was mediated through CXCR4 while the opposite
      effect was indirect. Together, our studies reveal for the first time a direct
      effect of SDF-1alpha on voltage-dependent membrane currents of neurons in brain
      slices and suggest that this chemokine may regulate MCH neuron activity.

PMID- 15733089
TI  - Delay of myelin formation in arylsulphatase A-deficient mice.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the
      deficiency of arylsulphatase A (ASA). This leads to the accumulation of the
      sphingolipid 3-O-sulphogalactosylceramide (sulphatide) and progressive
      demyelination in the nervous system of MLD patients. The mechanisms and
      development of pathology in the disease are still largely unknown. In this study
      we investigate how the inability to degrade sulphatide affects the formation of
      myelin in ASA-deficient (ASA-/-) mice. In mice at 2 weeks of age there was a
      substantial reduction in myelin basic protein (MBP) mRNA and protein. This was
      confirmed by an immunohistochemical analysis. MBP mRNA and protein, however,
      reach normal levels at 3 weeks of age. Proteolipid protein (PLP) and MAL mRNA
      were also reduced in ASA-/- mice at 2 weeks of age; whereas the level of PLP mRNA
      was normal at 26 weeks of age, MAL mRNA expression remained reduced up to this
      age. In situ hybridization revealed no significant changes in the number of
      myelinating oligodendrocytes or oligodendrocyte precursor cells in ASA-/- mice.
      These results suggest that oligodendrocyte differentiation was normal in ASA-/-
      mice. No differences were found in the expression of the sulphatide synthesizing
      enzymes cerebroside sulphotransferase and UDP-galactose : ceramide
      galactosyltransferase. Our data demonstrate a delay in myelin formation in ASA-/-
      mice. This raises the possibility that similar alterations in MLD patients may
      contribute to the pathology of the disease.

PMID- 15733090
TI  - Coupling of 5-HT1A autoreceptors to inhibition of mitogen-activated protein
      kinase activation via G beta gamma subunit signaling.
AB  - The 5-HT1A receptor is expressed presynaptically as the primary somatodendritic
      autoreceptor on serotonergic raphe neurons, and postsynaptically in several brain
      regions. Signaling of the 5-HT1A autoreceptor was studied in RN46A cells, a model
      of serotonergic raphe neurons that express endogenous 5-HT1A receptors. In
      undifferentiated RN46A cells stably transfected with the wild-type 5-HT1A
      receptor, 5-HT1A receptor activation inhibited forskolin-induced cyclic adenosine
      monophosphate (cAMP) formation (by 50%), increased [Ca2+]i, and induced a novel
      inhibition (up to 60%) of phospho-p42/p44-mitogen-activated protein kinase
      (MAPK). Upon differentiation of non-transfected or 5-HT1A-transfected RN46A
      cells, agonist-mediated inhibition of MAPK was enhanced. These actions were
      blocked by pretreatment with pertussis toxin indicating mediation via Gi/Go
      proteins and the calcium response was blocked by preactivation of protein kinase
      C (PKC). In cells overexpressing the G beta gamma scavenger carboxyl-terminal
      domain of G protein receptor kinase 2 (GRK-CT), 5-HT1A receptor activation
      inhibited cAMP formation, but coupling to calcium mobilization and inhibition of
      MAPK was abolished. The activity of 5-HT1A receptors containing mutations of PKC
      sites in the second (i2: T149A) or third intracellular loop (i3:
      T229A/S253G/T343A) was tested. At comparable levels of receptor expression, the
      signaling of the 5-HT1A i3 mutant was similar to the 5-HT1A wild-type receptor,
      while the i2 and quadruple (i2/i3) mutants failed to couple to G beta gamma
      mediated increase in [Ca2+]i or inhibition of MAPK, but did couple to G alpha i
      mediated inhibition of cAMP. Thus, the i2-domain of the 5-HT1A autoreceptor is
      crucial for coupling to G beta gamma subunits and their subsequent responses
      (e.g. calcium mobilization and inhibition of MAPK activity).

PMID- 15733092
TI  - Both oral and caudal parts of the spinal trigeminal nucleus project to the
      somatosensory thalamus in the rat.
AB  - Recent evidence has been accumulated that not only spinal trigeminal nucleus
      caudalis (Sp5C) neurons but also spinal trigeminal nucleus oralis (Sp5O) neurons
      respond to noxious stimuli. It is unknown, however, whether Sp5O neurons project
      to supratrigeminal structures implicated in the sensory processing of orofacial
      nociceptive information. This study used retrograde tracing with Fluorogold in
      rats to investigate and compare the projections from the Sp5O and Sp5C to two
      major thalamic nuclei that relay ascending somatosensory information to the
      primary somatic sensory cortex: the ventroposteromedial thalamic nucleus (VPM)
      and the posterior thalamic nuclear group (Po). Results not only confirmed the
      existence of contralateral projections from the Sp5C to the VPM and Po, with
      retrogradely labelled neurons displaying a specific distribution in laminae I,
      III and V, they also showed consistent and similar numbers of retrogradely
      labelled cell bodies in the contralateral Sp5O. In addition, a topographic
      distribution of VPM projections from Sp5C and Sp5O was found: neurons in the
      dorsomedial parts of Sp5O and Sp5C projected to the medial VPM, neurons in the
      ventrolateral Sp5O and Sp5C projected to the lateral VPM, and neurons in
      intermediate parts of Sp5O and Sp5C projected to the intermediate VPM. All
      together, these data suggest that not only the Sp5C, but also the Sp5O relay
      somatosensory orofacial information from the brainstem to the thalamus.
      Furthermore, trigemino-VPM pathways conserve the somatotopic distribution of
      primary afferents found in each subnucleus. These results thus improve our
      understanding of trigeminal somatosensory processing and help to direct future
      electrophysiological investigations.

PMID- 15733091
TI  - The N-terminal active centre of human angiotensin-converting enzyme degrades
      Alzheimer amyloid beta-peptide.
AB  - We reported recently that angiotensin-converting enzyme (ACE) significantly
      degraded amyloid beta-peptide (A beta) to inhibit aggregation and cytotoxicity of
      A beta in PC12h cells in vitro. On the other hand, others reported that ACE had
      two domains with highly homologous active centres, the N-domain and C-domain, but
      that they differed in their characteristics such as optimum chloride ion
      concentration, inhibition kinetics for various ACE inhibitors and rate of
      hydrolysis for many substrates. The aim of this study was to determine the
      specific ACE domain primarily responsible for degradation of A beta. For this
      purpose, a series of ACE recombinant proteins, each containing only one intact
      domain, was constructed and expressed in COS7. Our results showed that all ACE
      recombinant proteins obtained were enzymatically active in terms of angiotensin I
      cleavage. However, inhibition of A beta aggregation and cytotoxicity of the N
      domain were higher than those of the C-domain. Reverse-phase high-performance
      liquid chromatography analyses confirmed that the N domain degraded A beta. Our
      results indicate that the N domain of ACE is primarily responsible for the
      degradation of A beta.

PMID- 15733093
TI  - Mechanisms of somatostatin-evoked responses in neurons of the rat lateral
      amygdala.
AB  - The effects of somatostatin in the rat lateral amygdala (LA) in vitro were
      investigated through whole cell recording techniques. Somatostatin induced an
      inwardly rectifying K+ current in approximately 98% of LA projection neurons.
      Half-maximal effects were obtained by 189 nM somatostatin. The effects of
      somatostatin were insensitive to tetrodotoxin, reduced by Ba2+, occluded or
      abolished by the presence of nonhydrolysable GTP or GDP analogues, respectively,
      and blocked or mimicked by a somatostatin receptor type 2 antagonist (BIM-23627)
      or somatostatin receptor type 2 agonist (L-779,976), respectively, while
      somatostatin receptor type 1, 3 and 4 agonists were ineffective (L-797,591, L
      796,778, L-803,087). Responses to somatostatin were associated with membrane
      hyperpolarization and decrease in input resistance, resulting in a dampening of
      cell excitability. It is suggested that these cellular mechanisms contribute to
      the role of somatostatin in decreasing anxiety behaviour as well as to
      anticonvulsant and antiepileptogenic actions of somatostatin or somatostatin
      agonists in the amygdala.

PMID- 15733094
TI  - Dopamine modulation of spike dynamics in bursting neurons.
AB  - The pyloric network of the lobster stomatogastric ganglion is a prime example of
      an oscillatory neural circuit. In our previous study on the firing patterns of
      pyloric neurons we observed characteristic temporal structures termed 'interspike
      interval (ISI) signatures' which were found to depend on the synaptic
      connectivity of the network. Dopamine, a well-known modulator of the pyloric
      network, is known to affect inhibitory synapses so it might also tune the fine
      temporal structure of intraburst spikes, a phenomenon not previously
      investigated. In the recent work we study the DA modulation of ISI patterns of
      two identified pyloric neurons in normal conditions and after blocking their
      glutamatergic synaptic connections. Dopamine (10-50 microM) strongly regularizes
      the firing of the lateral pyloric (LP) and pyloric dilator (PD) neurons by
      increasing the reliability of recurrent spike patterns. The most dramatic effect
      is observed in the LP, where precisely replicated spike multiplets appear in a
      normally 'noisy' neuron. The DA-induced regularization of intraburst spike
      patterns requires functional glutamatergic inputs to the LP neuron and this
      effect cannot be mimicked by simple intracellular depolarization. Inhibitory
      synaptic inputs arriving before the bursts are important factors in shaping the
      intraburst spike dynamics of both the PD and the LP neurons. Our data reveal a
      novel aspect of chemical neuromodulation in oscillatory neural networks. This
      effect sets in at concentrations lower than those affecting the overall burst
      pattern of the network. The sensitivity of intraburst spike dynamics to preceding
      synaptic inputs also suggests a novel method of temporal coding in neural
      bursters.

PMID- 15733095
TI  - Increased spinal cord phosphorylation of extracellular signal-regulated kinases
      mediates micturition overactivity in rats with chronic bladder inflammation.
AB  - Spinal processing of somatosensory and viscerosensory information is greatly
      facilitated in some persistent pain states. Growing evidence suggests that the so
      called central sensitization depends in part on intracellular activation and
      signalling via specific MAP kinases. Here we studied the expression of
      phosphorylated extracellular signal-regulated kinases 1 and 2 (phosphoERK), the
      active form of these kinases, in spinal neurons following innocuous and noxious
      distension of non-inflamed and cyclophosphamide (CYP)-inflamed rat urinary
      bladders. Additionally, we investigated the nature of bladder primary afferents
      responsible for spinal ERK activation. Finally, we used a specific inhibitor of
      ERK phosphorylation to study the influence of these kinases on the bladder reflex
      activity of normal and inflamed bladders. Results indicated that, in non-inflamed
      rats, noxious but not innocuous bladder distension significantly increased spinal
      phosphoERK immunoreactivity from its normal very low level. However, in CYP
      inflamed rats, innocuous and noxious bladder distension significantly increased
      the number of spinal neurons immunoreactive to phosphoERK. ERK activation was
      rapid (within minutes) and transient. Desensitization of vanilloid-sensitive
      afferents by intravesical resiniferatoxin, a capsaicin analogue, did not decrease
      phosphoERK immunoreactivity in normal or CYP-inflamed rats. ERK inhibition by
      intrathecal PD 98059 had no effect on bladder reflex contractions of non-inflamed
      bladders but significantly decreased its frequency in inflamed animals. Our
      results suggest that spinal ERK intervene in acute and chronic inflammatory pain
      perception and mediate bladder reflex overactivity accompanying chronic bladder
      inflammation. In addition, bladder noxious input conveyed in vanilloid-resistant
      primary afferents is important to spinal ERK phosphorylation in both noninflamed
      and CYP-inflamed animals.

PMID- 15733096
TI  - Prolonged neglect following unilateral disruption of a prefrontal cortical-dorsal
      striatal system.
AB  - We investigated the potential function of the system formed by connections
      between the medial prefrontal cortex and the dorsomedial striatum in aspects of
      attentional function in the rat. It has been reported previously that
      disconnection of the same corticostriatal circuit produced marked deficits in
      performance of a serial, choice reaction-time task while sparing the acquisition
      of an appetitive Pavlovian approach behaviour in an autoshaping task (Christakou
      et al., 2001). Here, we hypothesized that unilateral disruption of the same
      circuit would lead to hemispatial inattention, contrasting with the global
      attention deficit following complete disconnection of the system. Combined
      unilateral lesions of the medial prefrontal cortex (mPFC) and the medial caudate
      putamen (mCPu) within the same hemisphere produced a severe and long-lasting
      contralesional neglect syndrome while sparing the acquisition of autoshaping.
      These results provide further evidence for the involvement of the medial
      prefrontal-dorsomedial striatal circuit in aspects of attentional function, as
      well as insight into the nature of neglect deficits following lesions at
      different levels within corticostriatal circuitry.

PMID- 15733097
TI  - Functional links between motor and language systems.
AB  - Transcranial magnetic stimulation (TMS) was applied to motor areas in the left
      language-dominant hemisphere while right-handed human subjects made lexical
      decisions on words related to actions. Response times to words referring to leg
      actions (e.g. kick) were compared with those to words referring to movements
      involving the arms and hands (e.g. pick). TMS of hand and leg areas influenced
      the processing of arm and leg words differentially, as documented by a
      significant interaction of the factors Stimulation site and Word category. Arm
      area TMS led to faster arm than leg word responses and the reverse effect, faster
      lexical decisions on leg than arm words, was present when TMS was applied to leg
      areas. TMS-related differences between word categories were not seen in control
      conditions, when TMS was applied to hand and leg areas in the right hemisphere
      and during sham stimulation. Our results show that the left hemispheric cortical
      systems for language and action are linked to each other in a category-specific
      manner and that activation in motor and premotor areas can influence the
      processing of specific kinds of words semantically related to arm or leg actions.
      By demonstrating specific functional links between action and language systems
      during lexical processing, these results call into question modular theories of
      language and motor functions and provide evidence that the two systems interact
      in the processing of meaningful information about language and action.

PMID- 15733099
TI  - Low doses of bromo- and iododeoxyuridine produce near-saturation labeling of
      adult proliferative populations in the dentate gyrus.
AB  - Cell proliferation can be detected by the incorporation of tritiated thymidine
      (3H-dT) or halopyrimidines during DNA synthesis in progenitor cells.
      Administration of two thymidine analogues at different times can further
      determine the cell-cycle kinetics of proliferating cells. Traditionally, this was
      done by combining bromodeoxyuridine (BrdU) immunocytochemistry and 3H-dT
      autoradiography, or by BrdU and iododeoxyuridine (IdU) double-labeling using two
      mouse antibodies. However, these methods either require lengthy exposure time or
      involve complicated histological procedures for differentiating between two
      antibodies of the same species. Here we report a simple and reliable method of
      distinguishing BrdU- and IdU-labeled cells by immunofluorescence. This method
      uses a mouse monoclonal antibody that recognizes both BrdU and IdU and a rat anti
      BrdU antibody that has no cross-reactivity with IdU. When combined with species
      specific secondary antibodies that are conjugated to different fluorophores, this
      method identifies BrdU- and IdU-incorporation as doubly and singly labeled cells,
      respectively. This method has broad applications. First, we demonstrate that this
      method can distinguish mouse cortical neurons generated on different embryonic
      days. Second, by administering IdU and BrdU at varying intervals, we used this
      method to calculate that the length of S-phase of neural progenitor cells in the
      adult mouse dentate gyrus is approximately 6 h. Finally, we show that a six-fold
      higher concentration of IdU detects only 10% more cells than the standard dose of
      BrdU (50 mg/kg) using the double-labeling method. These results suggest that the
      standard dose of BrdU is sufficient to label the majority of proliferative
      populations in the S-phase in pulse labeling experiments.

PMID- 15733100
TI  - Descending respiratory polysynaptic inputs to cervical and thoracic motoneurons
      diminish during early postnatal maturation in rat spinal cord.
AB  - Isolated brainstem-spinal cord preparations were used to explore the coexistence
      of a direct and an indirect descending drive from the brainstem respiratory
      centre to cervical and thoracic respiratory motoneurons in the neonatal Sprague
      Dawley rat. Polysynaptic spinal relay pathways from the respiratory centre were
      suppressed by selectively perfusing the cord with mephenesin (1 mM) or a solution
      enriched with Ca2+ and Mg2+. At birth, both direct and spinally relayed pathways
      are functional and contribute equally to the global descending respiratory drive.
      However, during the first postnatal week, significant maturational changes appear
      in the way the respiratory centre controls its target respiratory motoneurons in
      the cervical and thoracic spinal cord, with the direct respiratory drive becoming
      progressively predominant with maturation (from 50% to around 75% of the global
      descending command). The relative contributions of the monosynaptic and the
      polysynaptic spinal pathways may therefore have important implications for
      effective respiratory control during early postnatal development.

PMID- 15733098
TI  - Vitamin A is a necessary factor for sympathetic-independent rhythmic activation
      of mitogen-activated protein kinase in the rat pineal gland.
AB  - The circadian clock in the suprachiasmatic nucleus (SCN) controls day-to-day
      physiology and behavior by sending timing messages to multiple peripheral
      oscillators. In the pineal gland, a major SCN target, circadian events are
      believed to be driven exclusively by the rhythmic release of norepinephrine from
      superior cervical ganglia (SCG) neurons relaying clock messages through a
      polysynaptic pathway. Here we show in rat an SCN-driven daily rhythm of pineal
      MAPK activation that is not dependent on the SCG and whose maintenance requires
      vitamin A as a blood-borne factor. This finding challenges the dogma that SCG
      released norepinephrine is an exclusive mediator of SCN-pineal communication and
      allows the assumption that humoral mechanisms are involved in pineal integration
      of temporal messages.

PMID- 15733101
TI  - Neuromedin-U is regulated by the circadian clock in the SCN of the mouse.
AB  - Neuromedin-U (NMU) has been reported to drive several physiological or
      behavioural responses following i.c.v. injection of the peptide into the third
      ventricle of rodent brains. Many of these responses are mediated through a change
      in corticotrophin-releasing factor (CRF) output from the paraventricular nucleus
      (PVN). A number of the physiological or behavioural responses are regulated in a
      circadian manner, e.g. feeding. We have previously reported NMU gene expression
      in the suprachiasmatic nucleus (SCN) and NMU-2 receptor expression in the PVN,
      dorsal medial hypothalamus (DMH) and other regions of the mouse brain. We
      therefore hypothesized that NMU would be regulated by the circadian clock and may
      consequently drive a circadian rhythm of CRF expression in the PVN. Here we
      report that NMU is regulated in a circadian manner with peak expression during
      the light phase of a light-dark cycle. In C3H mice held in constant darkness, the
      NMU rhythm free runs with a period predicted by the free running period of
      locomotor activity in this mouse. The NMU mRNA transcript colocalizes with cells
      expressing AVP in the SCN and shows a coincident rhythm of expression with AVP.
      On the other hand, CRF did not express a circadian rhythm of expression in a
      light-dark cycle, although a rhythm was evident in constant darkness with a peak
      of expression prior to the rise of NMU in the same conditions. This would suggest
      that the circadian rhythm in NMU expression in the SCN does not drive a circadian
      rhythm in CRF in the PVN to be translated into physiological and behavioural
      responses mediated by NMU.

PMID- 15733102
TI  - Transient spatial deficit associated with bilateral lesions of the lateral
      mammillary nuclei.
AB  - The mammillary bodies have long been implicated in spatial memory, and lesions of
      this structure in rats can impair some spatial memory tasks. The mammillary
      bodies, however, comprise two main nuclei that have different
      electrophysiological and anatomical properties. It is therefore possible that
      they have different functions. The present study determined whether selective
      lesions of one of these components, the lateral mammillary nucleus, are
      sufficient to induce spatial memory deficits. While selective lateral mammillary
      nuclei lesions induced deficits on a working memory task in the water maze, this
      impairment was milder and not as persistent as that seen with complete mammillary
      body lesions. Furthermore, lateral mammillary nuclei lesions did not impair T
      maze alternation, which is sensitive to complete mammillary body lesions. From
      these results it appears that lesions confined to the lateral mammillary nuclei
      are sufficient to produce mild impairments when rapid, new spatial learning is at
      a premium. At the same time, the remaining mammillary nuclei also contribute to
      spatial learning, though this may be in a qualitatively different manner.

PMID- 15733104
TI  - Proliferative activity and genetic changes in adrenal cortical tumors examined by
      flow cytometry, fluorescence in situ hybridization and immunohistochemistry.
AB  - BACKGROUND: To determine differences in biological features among different
      adrenal tumors, we investigated the DNA ploidy, numerical chromosomal aberration
      and proliferative activity in human adrenal cortical neoplasms. METHODS: Our
      study included six adrenal cortical adenomas with Cushing syndrome, 12 adenomas
      with hyperaldosteronism, three non-functioning adenomas and three adrenal
      cortical carcinomas. Isolated nuclei from frozen samples were used for
      fluorescence in situ hybridization (FISH) analysis, and formalin-fixed, paraffin
      embedded tissues from the same materials were analyzed using flow cytometry (FCM)
      for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically
      with antibodies against Ki-67 and p53. For FISH analysis, we used an alpha
      centromeric enumeration probe for chromosome 17. RESULTS: The mean Ki-67 labeling
      index (LI) of adrenal cortical carcinomas was markedly higher than that of
      adrenal cortical adenomas (209.4 vs 8.7). In functional adrenal cortical
      adenomas, the LI was significantly lower in adenomas with hyperaldosteronism than
      in those with Cushing syndrome (P = 0.004), although FCM results indicated that
      tetraploid patterns were more frequently observed in the former type. Tumor size
      was significantly smaller in adenomas with hyperaldosteronism than in those with
      Cushing syndrome (P = 0.004). Chromosome 17 showed disomy in all adrenal cortical
      adenomas, whereas chromosome 17 abnormalities were found in two of three adrenal
      cortical carcinomas. Only the latter two cases strongly expressed p53 protein.
      CONCLUSIONS: Our study characterized various biological features of benign and
      malignant adrenal cortical tumors. The use of a combination of markers might
      provide additional information to assist our understanding of the clinical
      behavior of an individual adrenal cortical tumor.

PMID- 15733105
TI  - Efficacy and safety of laparoscopic surgery for pheochromocytoma.
AB  - OBJECTIVE: Laparoscopic surgery for primary aldosteronoma and Cushing's syndrome
      is well established. We report on our experiences with laparoscopic adrenalectomy
      for pheochromocytoma, and assess the efficacy and safety of the laparoscopic
      approach. METHODS: Between April 1998 and April 2003, a total of 23 patients
      underwent laparoscopic adrenalectomy for pheochromocytoma at Chiba University
      Hospital and Yokohama Rosai Hospital, Japan. We compared the surgical outcomes of
      these patients with those of 106 patients with adrenal tumors due to other
      pathologies who underwent laparoscopic adrenalectomy during the same period.
      RESULTS: The mean tumor size of pheochromocytoma was 4.96 cm. Mean operative time
      was 192.7 min, and mean estimated blood loss was 130 mL. Neither mean operative
      time nor mean estimated blood loss was greater for patients with
      pheochromocytoma. Intraoperative hypertension (systolic blood pressure > 180
      mmHg) occurred in 39.1% (9/23) of patients with pheochromocytoma. During the
      follow-up period, there were no mortalities or recurrences of endocrinopathy.
      CONCLUSIONS: Laparoscopic adrenalectomy for pheochromocytoma is a safe and
      minimally invasive procedure.

PMID- 15733106
TI  - Laparoscopic adrenalectomy in patients with large adrenal tumors.
AB  - OBJECTIVES: The maximum size of adrenal tumors that should be removed by
      laparoscopic adrenalectomy is controversial. We conducted a retrospective
      comparison of the results of laparoscopic adrenalectomy between patients with
      adrenal tumors > or =6 cm ('large tumors') and patients with adrenal tumors <6 cm
      ('small tumors'). METHODS: The participants in the study were 16 patients with
      large tumors and 111 patients with small tumors. The patients comprised 59 men
      and 68 women (mean age, 49.0 years; age range, 23-79) with varying diagnoses. Of
      the 16 patients with large tumors, five had Cushing's syndrome, four had
      pheochromocytomas, six had a non-functional tumor and one had malignant lymphoma.
      Adrenal tumors were confirmed by hormonal assays, biochemical tests and computed
      tomography. Of the 16 large tumors, five tumors were on the right and 11 were on
      the left. RESULTS: We found no significant differences in general demographic
      parameters between patients with large and small tumors. The mean duration of
      surgery was not significantly different between two groups. (large tumors, 210
      min; small tumors,175 min). The mean volume of blood loss was 212 mL for large
      tumors and 30 mL for small tumors (P < 0.001, significant difference). There was
      no significant difference in time until walking, duration of hospitalization or
      number of using analgesics used. The time to first oral intake of group 1 (<6 cm)
      was significantly shorter than group 2 (> or =6 cm). Tumor size (> or =7.5 cm)
      was an independent predictor of a longer operation and greater blood loss in
      large tumors. CONCLUSIONS: Laparoscopic adrenalectomy for large tumors was safe
      and minimally invasive.

PMID- 15733108
TI  - Adverse drug reactions of intravesical bacillus Calmette-Guerin instillation and
      risk factors of the development of adverse drug reactions in superficial cancer
      and carcinoma in situ of the bladder.
AB  - BACKGROUND: We examined the incidence and severity of adverse drug reactions
      following intravesical bacillus Calmette-Guerin (BCG) instillation for
      superficial bladder cancer including carcinoma in situ. We investigated the
      relationship between adverse drug reactions and patient background to clarify
      risk factors for the development of adverse drug reactions. METHODS: A total of
      123 patients who underwent intravesical BCG instillation for treatment and
      prophylaxis between April 1997 and June 2000 were included in this study. Adverse
      drug reactions were divided into local and systemic categories and the severity
      of reactions was classified according to the presence or absence of postponement
      or discontinuation of instillation, with or without treatment for the reaction
      itself. RESULTS: Of 123 patients, 95.9% showed adverse drug effects and 50.4%
      needed some sort of treatment. Discontinuation of instillation due to adverse
      drug reactions was observed in nine patients. Regarding the necessity of
      treatment for adverse drug effects, the purpose of instillation and BCG dose were
      independent significant factors on multivariate analysis. CONCLUSION: Although
      there was a high rate of adverse drug reactions after intravesical BCG
      instillation, the rate of discontinuation of instillation was not high and
      serious adverse reactions were rare. The scale of the present study was small,
      but these results suggest that BCG instillation was well tolerated. When
      instillation is being performed for the purpose of treatment, and the BCG dose is
      80 mg, greater attention might be needed to monitor for the development of
      adverse drug effects.

PMID- 15733107
TI  - Effects of potassium-magnesium citrate supplementation on cytosolic ATP citrate
      lyase and mitochondrial aconitase activity in leukocytes: a window on renal
      citrate metabolism.
AB  - BACKGROUND: An increase in urinary citrate excretion is associated with a
      decrease in activity of renal cortical cytosolic ATP citrate lyase (ACL) and
      mitochondrial aconitase (m-aconitase). Because potassium-magnesium citrate causes
      an increase in urinary citrate excretion, we decided to assess its effects on ACL
      and m-aconitase in the leukocytes of renal stone patients. METHODS: Twenty male
      renal stone patients were supplemented with potassium-magnesium citrate twice
      daily (i.e. 42 mEq potassium, 21 mEq magnesium, and 63 mEq citrate per day) for a
      period of 1 month. Two 24-h urine and one 15-mL heparinized blood samples were
      collected from each patient before and after supplementation. Urine samples were
      analyzed for relevant biochemical compositions. Leukocytes were separated from
      blood samples by centrifugation and assayed for ACL and m-aconitase activity.
      RESULTS: Supplementation with potassium-magnesium citrate significantly increased
      urinary pH (P < 0.005) and excretions of potassium (P < 0.001), magnesium (P <
      0.001) and citrate (P < 0.0001). The activity of both ACL and m-aconitase were
      significantly decreased (P < 0.004 and P < 0.02 respectively). The decrease in
      ACL activity was inversely correlated with an increase in urinary excretion of
      both potassium (r = -0.620, P < 0.0001) and citrate (r = -0.451, P < 0.004). A
      similar inverse correlation was observed between m-aconitase activity and urinary
      excretion of citrate (r = -0.322, P < 0.043). CONCLUSION: Changes in enzyme
      activity, related to citrate metabolism in leukocytes, might reflect the status
      of renal tubular cells.

PMID- 15733109
TI  - Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node
      metastasis of transitional cell carcinoma of the bladder.
AB  - PURPOSE: It has been found that expression of vascular endothelial growth factor
      C (VEGF-C) in several carcinomas is significantly associated with angiogenesis,
      lymphangiogenesis and regional lymph node metastasis. However, VEGF-C expression
      in bladder transitional cell carcinoma (TCC) has not yet been reported. To
      elucidate the role of VEGF-C in bladder TCC, we examined VEGF-C expression in
      bladder TCC and pelvic lymph node metastasis specimens obtained from patients who
      underwent radical cystectomy. METHODS: Eighty-seven patients who underwent
      radical cystectomy for clinically organ-confined TCC of the bladder were enrolled
      in the present study. No neoadjuvant treatments, except transurethral resection
      of the tumor, were given to these patients. The VEGF-C expressions of 87 bladder
      tumors and 20 pelvic lymph node metastasis specimens were examined
      immunohistochemically and the association between VEGF-C expression and
      clinicopathological factors, including angiogenesis as evaluated by microvessel
      density (MVD), was also examined. RESULTS: Vascular endothelial growth factor-C
      expression was found in the cytoplasm of tumor cells, but not in the normal
      transitional epithelium. Vascular endothelial growth factor-C expression was
      significantly associated with the pathological T stage (P = 0.0289), pelvic lymph
      node metastasis (P < 0.0001), lymphatic involvement (P = 0.0008), venous
      involvement (P = 0.0002) and high MVD (P = 0.0043). The multivariate analysis
      demonstrated that VEGF-C expression and high MVD in bladder TCC were independent
      risk factors influencing the pelvic lymph node metastasis. Moreover, the patients
      with VEGF-C-positive tumors had significantly poorer prognoses than those with
      the VEGF-C-negative tumors (P = 0.0087) in the univariate analysis. The
      multivariate analysis based on Cox proportional hazard model showed that the
      independent prognostic factors were patient age (P = 0.0132) and pelvic lymph
      node metastasis (P = 0.0333). CONCLUSION: The present study suggests that VEGF-C
      expression is an important predictive factor of pelvic lymph node metastasis in
      bladder cancer patients.

PMID- 15733110
TI  - Doxazosin for benign prostatic hyperplasia: an open-label, baseline-controlled
      study in Korean general practice.
AB  - BACKGROUND: Few studies have reported the treatment of benign prostatic
      hyperplasia (BPH) in Asian patients. We assessed the safety and efficacy of
      doxazosin, a selective alpha1-adrenoceptor antagonist, in the treatment of Korean
      patients with symptomatic BPH. METHODS: Two hundred and ninety-five men, aged 48
      years or older with clinical BPH, were enrolled in a 12-week, open-label,
      baseline-controlled, dose-titration, multicenter study. A 2-week, single-blind,
      placebo run-in was followed by 10 weeks of doxazosin treatment, initially
      administered at 1 mg/day, with upward titrations (2, 4, or 8 mg/day) at 2-week
      intervals. The international prostate symptom score (IPSS) was used to assess
      efficacy after 4, 6, and 10 weeks of active treatment. RESULTS: The intent-to
      treat (ITT) population comprised 249 patients (mean age 63.6 years). Doxazosin
      significantly reduced the mean total IPSS by 48%; similarly, the obstructive and
      irritative subscores were reduced from baseline by 51% and 39%, respectively (P <
      0.001 for all scores: Wilcoxon rank sum test). In a subset analysis of 170
      normotensive and 78 hypertensive patients, significant reductions in mean
      systolic and diastolic blood pressures relative to baseline were observed only in
      the hypertensive subset (P < 0.01). Similar results in mean IPSS were observed in
      older (> or =65 years, n = 100) and younger (45-64 years, n = 140) patients, as
      well as between normotensive and hypertensive patients. Thirty-nine patients
      reported adverse events: The most frequent were dizziness, dyspepsia, asthenia,
      somnolence, and dry mouth. CONCLUSIONS: The efficacy and safety of doxazosin
      treatment for BPH were confirmed in this Asian population. Significant
      improvements in total IPSS, as well as obstructive and irritative subscores, were
      observed.

PMID- 15733111
TI  - Single-nucleotide polymorphisms in the 17beta-hydroxysteroid dehydrogenase genes
      might predict the risk of side-effects of estramustine phosphate sodium in
      prostate cancer patients.
AB  - BACKGROUND: Estramustine phosphate sodium (EMP) frequently causes side-effects
      such as gastrointestinal discomfort, nausea, and edema in extremities. We
      analyzed single nucleotide polymorphisms (SNP) in the 17beta-hydroxysteroid
      dehydrogenase (HSD17B) genes, which are involved in the metabolism of EMP, to
      predict the risk of EMP side-effects in prostate cancer patients. METHODS: We
      performed genotyping of SNP in the HSD17B genes of 44 Japanese patients with
      newly diagnosed prostate cancer. The association of SNP and individual EMP side
      effects was evaluated. RESULTS: Peripheral edema occurred more frequently in
      patients with C/C genotype of IMS-JST123219 than in those with C/G genotype (OR:
      5.47, 95% CI: 1.27-23.64). Haplotype analysis showed that appetite loss was
      associated with the G allele of IMS-JST123219 and the T allele of IMS-JST123218
      (OR: 9.13, 95% CI: 1.15-72.76). CONCLUSIONS: These preliminary data demonstrated
      that analyses of SNP in the HSD17B genes might predict the occurrence of side
      effects from EMP.

PMID- 15733112
TI  - Impact of hormonal therapy prior to radical prostatectomy on the recovery of
      quality of life.
AB  - BACKGROUND: We investigated the changes in health-related quality of life (HRQOL)
      in patients who underwent prostatectomy (RP) with or without neoadjuvant hormonal
      therapy (NHT). METHODS: A total of 72 patients undergoing direct RP (DRP group)
      and 26 patients receiving neoadjuvant hormonal therapy (NHT group) were enrolled
      in the present study. The baseline interview was conducted before RP (not
      initiation of therapy). Follow-up interviews were conducted in person at
      scheduled study visits of 3, 6, and 12 months after surgery. We measured general
      and disease specific HRQOL with the Medical Outcomes Study 36-Item Short Form and
      University of California, Los Angeles Prostate Cancer Index, respectively.
      RESULTS: At baseline, the NHT group scored statistically lower for not only
      sexual function (P < 0.001), but also the general HRQOL, such as role limitations
      due to physical problems (P = 0.007), social function (P = 0.045) and mental
      health (P = 0.034), than the DRP group. The NHT group reported lower scores in
      social function and mental health at 3 months (P = 0.040 and 0.006,
      respectively). Patients who received NHT for more than 3 months continued to show
      significantly lower scores for some HRQOL domains 12 months later. CONCLUSION:
      Neoadjuvant hormonal therapy may decrease not only sexual function, but also
      general HRQOL before surgery. The recovery of HRQOL appeared to be further
      prolonged in patients who received long-term NHT.

PMID- 15733113
TI  - Preoperative prediction of final pathological features is not improved by the
      free-to-total prostate-specific antigen ratio in Japanese men with clinically
      localized prostate cancer.
AB  - BACKGROUND: The objective of the present study was to determine whether the
      percentage of free/total prostate-specific antigen (f/tPSA) in patients scheduled
      to undergo radical prostatectomy for clinically localized prostate cancer can
      preoperatively predict organ-confined versus extraprostatic disease. METHODS:
      Serum levels of fPSA and tPSA were measured in 97 patients with clinically organ
      confined disease before they underwent radical prostatectomy. The relationships
      of tPSA, f/tPSA and the pathological stage of the prostatectomy specimens were
      analyzed. Furthermore, the ability of f/tPSA to predict the pathological features
      was compared with those of tPSA and systematic biopsy findings. RESULTS: Organ
      confined and extraprostatic extension diseases were present in 51 and 46 men,
      respectively. tPSA in patients with extraprostatic diseases was significantly
      higher than that in those with organ-confined diseases; however, there was no
      significant difference in f/tPSA between these two groups. There was also a
      significant difference in tPSA levels at each pathological stage, while f/tPSA
      did not parallel the pathological stage. Furthermore, there was no additional
      information concerning the extent of prostate cancer obtained when f/tPSA was
      combined with tPSA or with the percent of positive biopsy cores, which is the
      most significant predictor of the extent of prostate cancer among factors
      associated with systematic biopsy. CONCLUSION: f/tPSA could not predict the final
      pathological features in patients with clinically localized prostate cancer
      before radical prostatectomy. Moreover, the predictive value provided by tPSA or
      systematic biopsy findings was not improved by combined analysis with f/tPSA.

PMID- 15733114
TI  - Sexual behavior survey and screening for chlamydia and gonorrhea in university
      students in South Korea.
AB  - BACKGROUND: The purpose of the present study was to define the prevalence of
      genital Chlamydia trachomatis and Neisseria gonorrhoeae infections and status of
      sexual risk behavior among university students (18-25 years old) in the capital
      region of South Korea. METHODS: Participants filled out a self-administered
      questionnaire related to sexuality. First-void urine was analyzed for chlamydial
      and gonococcal infection by strand displacement amplification (BDProbTecET, BD
      Diagnostic Systems, MD). RESULTS: A total of 622 students from 15 colleges in
      three universities took part in the study. The median age was 21 and 39.1% of
      them reported having sexual intercourse at least once. The prevalence of C.
      trachomatis among sexually active men and women was 8.4% and 10.6%, respectively.
      Gonococcal infection was noted in one symptomatic male. Factors significantly
      associated with infection were the number of sexual partners during past year and
      lifetime and condom use. CONCLUSIONS: This is the first sexually transmitted
      infection (STI) screening in university students in South Korea. Urine-based STI
      screening was both feasible and acceptable in university students in South Korea.
      It should be considered a routine part of programs to control STI nationally.

PMID- 15733115
TI  - Comparison of microvessel densities in rat prostate tissues treated with
      finasteride, bicalutamide and surgical castration: a preliminary study.
AB  - BACKGROUND: A group of anti-androgens with different mechanisms of action and
      adverse effects have been investigated in patients with gross hematuria related
      to benign prostate hyperplasia; however, there is not yet any consensus about the
      standard management of these patients. The present study aims to identify if any
      one type of the hormonal intervention is superior in terms of the suppression of
      microvessel formation in the prostate. MATERIALS AND METHODS: A total of 28
      mature, healthy male Sprague-Dawley rats (300 +/- 50 g) were used in this study.
      The rats were randomly assigned to one of four groups (n = 7 per group). The
      effects of three different hormonal therapies on angiogenesis and
      microvascularity in rat ventral prostate were compared. Groups 1 and 2 were
      treated for 28 days with finasteride and bicalutamide, respectively, and rats
      from Group 3 underwent surgical castration. Following treatment, all rats
      included in the study underwent dissection of the ventral prostate and
      immunohistochemical analysis of microvessel density by factor VIII-related
      antigen. RESULTS: The mean number of microvessels in the finasteride and
      bicalutamide groups was 24.5 (+/-8.44 SE) and 27 (+/-9.89 SE) respectively. In
      contrast, the castration and control groups had microvessel numbers of 12.9 (+/
      5.35 SE) and 40.3 (+/-5.03 SE) respectively. Differences were statistically
      significant between all three treatment groups and the controls (P < 0.005); the
      number of microvessels in rat prostate tissues of the control group was
      significantly higher than the treatment groups. Mean microvessel densities in the
      bicalutamide and finasteride groups were significantly higher than microvessel
      densities in the castration group (P < 0.005). There was no statistically
      significant difference between mean microvessel number in rat prostate tissue
      treated with finasteride or bicalutamide (P > 0.05). CONCLUSIONS: Even though
      finasteride was not as effective as castration in reducing microvessel number,
      its effect was equal to that of bicalutamide in terms of suppressing the
      angiogenesis in prostatic tissue. Based on the findings of the present study,
      finasteride might offer a viable option in the management of macroscopic
      hematuria by inhibition of microvessel formation within the prostatic tissue.
      Further clinical studies are warranted.

PMID- 15733116
TI  - Sarcomatoid carcinoma of the renal pelvis with giant cell tumor-like features:
      case report with immunohistochemical findings.
AB  - Sarcomatoid transitional cell carcinoma is a rare entity, in which a malignant,
      overtly epithelial component coexists with areas having a sarcoma-like
      appearance. Histological distinction of sarcomatoid carcinomas from
      carcinosarcomas is often difficult and immunohistochemistry is a helpful
      diagnostic adjunct in the correct diagnosis. In the present report, we describe
      an uncommon case of sarcomatoid transitional cell carcinoma of the renal pelvis,
      associated with giant cell tumor-like features. Immunoperoxidase staining for
      cytokeratin was positive in spindle cell component, indicating an epithelial
      origin. The carcinomatous component showed a diffuse membranous reactivity for E
      cadherin, whereas the reactivity was sporadic and weaker in the sarcomatoid
      component, suggesting that the decrease of E-cadherin expression might be
      associated with the acquisition of sarcomatous morphology. Osteoclast-like
      multinucleated giant cells were positive for CD68 and negative for p53
      oncoprotein, suggesting that they represent a non-neoplastic component that is
      reactively induced in the tumor stroma.

PMID- 15733117
TI  - Epithelioid angiomyolipoma of the kidney.
AB  - Epithelioid angiomyolipoma is a recently recognized variant of angiomyolipoma,
      which is characterized by the presence of polygonal cells with densely
      eosinophilic cytoplasm and varying degrees of nuclear atypia. Only a relatively
      small number of cases of epithelioid angiomyolipoma of the kidney have been
      reported in the literature. We report a case of epithelioid angiomyolipoma of the
      kidney that occurred in a 38-year-old woman. The tumor was composed of diffuse
      sheets of epithelioid cells, adipocytes and only scattered thick-walled blood
      vessels. The epithelioid cells had pleomorphic and hyperchromatic nuclei with
      densely eosinophilic cytoplasm. Hemorrhage, necrotic foci and clusters of foamy
      macrophages were present. HMB-45, CD117 (c-kit) and CD68 were detected in the
      epithelioid cells. There was no expression of cytokeratin, epithelial membrane
      antigen or desmin. The patient showed no evidence of recurrence or metastatic
      disease 9 months after nephrectomy.

PMID- 15733118
TI  - Successful treatment of chemo-refractory pulmonary metastases of renal pelvic
      cancer by second-line chemotherapy including gemcitabine followed by salvage
      surgery.
AB  - A 51-year-old woman developed multiple pulmonary metastases after receiving
      nephroureterectomy and two cycles of adjuvant chemotherapy for the treatment of
      renal pelvic transitional cell carcinoma. All metastases disappeared after four
      cycles of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC)
      chemotherapy followed by radiotherapy; however, 8 months later two pulmonary
      metastases recurred. The patient was entered into a phase I study of combination
      chemotherapy with gemcitabine, etoposide and cisplatin, designed for
      chemorefractory urothelial cancer. The lung masses showed significant reduction
      after two cycles of this chemotherapy; following salvage surgery, the patient has
      been well with no evidence of recurrence for more than 3 years.

PMID- 15733119
TI  - Management of gestational nephrolithiasis in the presence of a bicornuate uterus
      and pelvic kidney.
AB  - A 39-year-old para 0(+1) woman with known nephrolithiasis within a left-sided
      pelvic kidney presented with left-sided renal colic at 7 weeks gestation. She had
      a previous miscarriage due to a bicornuate uterus. Ultrasound and magnetic
      resonance urography confirmed an incomplete obstruction of the left upper renal
      tract which was relieved by percutaneous nephrostomy. She presented again at 14
      weeks with renal colic and minimal output. An ultrasound confirmed recurrent
      hydronephrosis and a nephrostogram showed that the catheter had retracted almost
      completely from the collecting system. This was considered to be due to the
      upward pressure of the enlarging uterus on the catheter, which had been fixed
      externally to the skin. This problem was obviated by not securing the replacement
      nephrostomy tube to the skin. She developed pre-eclamptic toxaemia and gave birth
      at 35 weeks gestation by caesarean section. The calculus was later dissolved
      using extra-corporeal shockwave lithotripsy.

PMID- 15733120
TI  - Papillary adenocarcinoma of the renal pelvis and ureter producing
      carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125.
AB  - We report a case of advanced renal pelvis and ureter adenocarcinoma producing
      carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and
      carbohydrate antigen 125 (CA125). A 72-year-old woman was diagnosed with right
      renal pelvic and ureter tumor with para-aortic lymph node swelling. Biopsy of the
      ureteral mass revealed papillary adenocarcinoma. Serum levels of CEA, CA19-9 and
      CA125 were extremely elevated. The patient was successfully treated with
      paclitaxel/carboplatin chemotherapy followed by surgery.

PMID- 15733121
TI  - Placement of a urethral catheter into the ureter: An unexpected complication
      after retropubic suspension.
AB  - We describe an unusual complication caused by urethral catheterization which, to
      our knowledge, has not yet been reported. A 16 Fr urethral balloon catheter was
      unintentionally placed into the left ureter through the ureteral orifice in a 51
      year-old woman following retropubic suspension surgery for stress urinary
      incontinence. After retrograde urography from the urethral catheter and removal
      of the catheter, reoperation was performed and a double pig-tail ureteral stent
      was placed in the left ureter with subsequent proper replacement of a urethral
      catheter. The patient had uneventful postoperative recovery. Although the
      presented accident was an unexpected complication which might be associated with
      anatomical changes resulting from colposuspension, we should have confirmed the
      catheter position intraoperatively.

PMID- 15733122
TI  - Giant retroperitoneal liposarcoma.
AB  - Liposarcomas are one of the most common soft tissue sarcomas of adulthood.
      Liposarcomas are remarkable because of their frequently large size. We report a
      case with an extremely large dedifferentiated liposarcoma that weighed 18 kg.
      Although it was capsulated and could be excised en bloc, the patient suffered a
      relapse 9 months later and died 1 year after the operation.

PMID- 15733123
TI  - Testicular natural killer T-cell lymphoma.
AB  - Primary testicular lymphomas account for less than 5% of all testicular
      neoplasms. Testicular natural killer (NK)/T-cell lymphomas are exceptional and
      have a very poor prognosis. We report the case of a 30-year-old French Caucasian
      man with testicular NK/T-cell lymphoma of the following immunophenotype: CD2+,
      CD3epsilon+ and CD56+. Despite intensive chemotherapy, the disease progressed
      rapidly, with death occurring 2 months after diagnosis.

PMID- 15733124
TI  - Nutritional hypogonadotropic hypogonadism presented with decreased ejaculatory
      volume.
AB  - Abstract A 19-year-old male college student presented with decreased ejaculatory
      volume. Endocrinological examinations demonstrated a hypogonadotropic
      hypogonadism (HH) caused by a gonadotropin-releasing hormone deficiency from the
      hypothalamus. Cranial magnetic resonance imaging did not demonstrate any
      abnormalities. The possible causative factor of this adult-onset HH was excessive
      weight-loss (-26% in 1 year) due to inadequate food intake and an irregular
      lifestyle. Semen analyses and serum gonadotropin and testosterone values
      gradually improved as the patient became accustomed to his new life and regained
      weight.

PMID- 15733125
TI  - Infection-induced urethral defect treated by urethral reconstruction with a
      radial forearm flap.
AB  - Abstract A 47-year-old man was admitted with the chief complaint of a urethral
      defect. An approximately 17-cm defect of the urethra seemed to have been occurred
      by the infection of implanted foreign bodies in the penile skin. Reconstruction
      of the urethra and the ventral skin was performed with a free radial forearm
      flap. A fistula formed at the proximal anastomosis after the operation, but was
      controlled conservatively. Urethral stricture at the proximal anastomosis
      subsequently developed. A urethral stent made of shape memory alloy was placed
      with the preservation of voiding function.

PMID- 15733126
TI  - Congenital prepubic sinus: a variant of dorsal urethral duplication (Stephens
      type 3).
AB  - Abstract A 3-year-old boy was admitted for yellowish discharge from a tiny
      opening in the midline prepubic area on the dorsal base of the penis. No other
      symptom related to the genitourinary tract was noted. Sinuousgraphy showed a non
      communicating sinus tract with the urinary tract. At surgical exploration,
      through a diamond-shaped incision, a 4.5 cm-long sinus was found that ended
      blindly as a fibrous cord at the anterior surface of the pubic symphisis.
      Histologically, it was lined by stratified squamous epithelium and surrounded by
      bundles of smooth muscle and collagen. According to Stephens' classification, the
      sinus appears to be a variant of dorsal urethral duplication of Stephens type 3.

PMID- 15733127
TI  - Novel technique for correcting penile curvature with severe hypospadias; ventral
      lengthening with tunica vaginalis flap patching.
AB  - The adequate correction of penile curvature is essential for successful
      hypospadias surgery. We describe a novel technique to correct severe penile
      curvature with a tunica vaginalis flap on the penile ventrum. We applied a tunica
      vaginalis flap to lengthen the ventral aspect of the tunica albuginea in two boys
      with significant curvature and proximal hypospadias. Tunica vaginalis flap
      patching to the ventral aspect of the penis is safe and technically feasible. If
      penile curvature is severe or the penis is small in hypospadiac patients,
      lengthening the ventral aspect using a tunica vaginalis flap is likely to expand
      instead of dorsal plication or ventral graft.

PMID- 15733129
TI  - Effect of implant angulation upon retention of overdenture attachments.
AB  - INTRODUCTION: Overdentures supported and retained by endosteal implants depend
      upon mechanical components to provide retention. Ball attachments are frequently
      described because of simplicity and low cost, but retentive capacity of these
      components may be altered by a lack of implant parallelism. PURPOSE: The aim of
      this in vitro study was to investigate the retention of gold and titanium
      overdenture attachments when placed on ball abutments positioned off-axis.
      METHODS AND MATERIALS: Four ball abutments were hand-tightened onto ITI dental
      implants and placed in an aluminum fixture that allowed positioning of the
      implants at 0 degrees, 10 degrees, 20 degrees, and 30 degrees from a vertical
      reference axis. Gold and titanium matrices were then coupled to the ball
      abutments at various angles and then subjected to pull tests at a rate of 2
      mm/second; the peak loads of release (maximum dislodging forces) were recorded
      and subjected to statistical analyses. A balanced and randomized factorial
      experimental design testing procedure was implemented. RESULTS: Statistically
      significant differences in retention of gold matrices were noted when ball
      abutments were positioned at 20 degrees and 30 degrees , but not at 0 degrees and
      10 degrees. Statistically significant differences were noted among the titanium
      matrices employed for the testing procedure, as well as for the 4 ball abutments
      tested. Angle was not a factor affecting retention for titanium matrices.
      CONCLUSIONS: (1) The gold matrices employed for the testing procedures exhibited
      consistent values in retention compared to titanium matrices, which exhibited
      large variability in retention. (2) Angle had an effect upon the retention of
      gold matrices, but not for titanium matrices.

PMID- 15733130
TI  - Flexural strengths of denture base resin repaired with autopolymerizing resin and
      reinforcements after thermocycle stressing.
AB  - PURPOSE: Fracture of an acrylic denture base is a common problem in prosthodontic
      practice. Although various reinforcement methods have been used, when a fractured
      denture base is repaired with autopolymerizing resin recurrent fractures
      frequently occur at the repairing interface or adjacent areas. The purpose of
      this study was to evaluate the maximum flexural load of denture base resin
      repaired with autopolymerizing resin and several reinforcement systems after
      thermocycle stressing. MATERIALS AND METHODS: Rectangular (10 x 70 x 3 mm)
      flexural specimens were fabricated by repairing a pair of heat-cured denture base
      resin specimens using autopolymerizing resin and a series of reinforcement
      materials. The materials included 4 metal wires and a woven glass fiber. Each
      reinforcement was embedded in the center of the specimens. Flexural specimens
      repaired without reinforcement were prepared as controls. Specimens were
      subjected to 50,000 thermocycles (4 approximately 60 degrees C, 1-minute dwell
      time). A 3-point flexural test was carried out by loading the center of the
      repaired site at 5 mm/minute crosshead speed with 50 mm span jig supports. The
      load necessary to cause fracture was recorded for each specimen. All data were
      statistically analyzed using ANOVA and the Bonferroni/Dunn test (alpha < 0.05).
      RESULTS: The average load to fracture of specimens repaired with nonreinforced
      autopolymerizing resin was 68.4 N after 50,000 thermocycles. Specimens reinforced
      with 1.2 mm diameter stainless steel wire exhibited the highest value (89.8 N).
      The value for specimens reinforced with 1.2 mm diameter Co-Cr-Ni wire was 86.6 N.
      These fracture loads were significantly higher than those for specimens without
      reinforcement (p < 0.05). Low elasticity reinforcement, such as pure titanium
      wires, woven metal wire, and woven glass fiber were not effective in increasing
      the load to fracture values of flexural specimens. CONCLUSIONS: Specimens
      reinforced with 1.2 mm diameter stainless steel wires or Co-Cr-Ni wires resulted
      in significantly higher loads to fracture as compared to specimens without
      reinforcement. The use of pure titanium wire, woven metal wire, and woven glass
      fiber did not improve the fracture loads.

PMID- 15733131
TI  - The influence of water storage on durometer hardness of 5 soft denture liners
      over time.
AB  - PURPOSE: This laboratory study investigated the influence of water storage on the
      durometer hardness of 2 RTV and 3 HTV soft denture liners over a 1-year period.
      MATERIALS AND METHODS: Five soft denture liners were used: 2 HTV silicone rubber
      (Luci-Sof and Molloplast-B), 1 RTV silicone rubber (Tokuyama), 1 HTV
      polyphosphazene (Novus), and an RTV plasticized acrylic (PermaSoft) that uses a
      surface sealer. They were processed following manufacturers' instructions, cured,
      and stored in tap water at 37 degrees C. The water was changed every 2 weeks.
      Five durometer A hardness measurements were made at logarithmically spaced
      intervals of 16.7 minutes, 27.8 hours, 11.6 days, 34.7 days, 115 days, and 347
      days. Repeated measures analysis of variance (MANOVA), one-way analysis of
      variance (ANOVA), Pillai trace statistic, the difference scores (last-first)
      among the groups, and the Tamhane T2 multiple comparison test were used to
      compare the groups over time, all on SPSS V. 7.5 and 9.0. RESULTS: The order of
      highest initial indentation hardness was Luci-Sof, Molloplast-B, Novus (H(D)= 38
      to 33). Tokuyama and PermaSoft as a group were softer (H(D)= 18 to 22). Tokuyama
      Soft Relining changed the least over 347 days, followed by Luci-Sof, Novus,
      Molloplast-B, and PermaSoft in that order (p < or = 0.05). Within the PermaSoft
      group, sealer applied only once changed the least over 347 days, followed by no
      sealer, and then sealer applied every month (p < 0.0005). CONCLUSIONS: After 347
      days of water storage, Tokuyama had the lowest indentation hardness changes,
      followed by Luci-Sof, Novus, PermaSoft with sealer applied once; Molloplast-B,
      PermaSoft without sealer; and PermaSoft with sealer applied every month. All HTV
      soft denture liners had higher indentation hardness than RTV liners initially.
      After 347 days, PermaSoft without sealer and with sealer every month became the
      hardest.

PMID- 15733132
TI  - Dimensional accuracy of 7 die materials.
AB  - PURPOSE: The purpose of this study was to compare the linear dimensional accuracy
      and the handling characteristics of 7 die materials. MATERIALS AND METHODS: A
      master die analogous to a complete veneer crown preparation was machined from
      medical grade stainless steel, and 3 measurements (1: vertical; 2 and 3:
      horizontal) were made from 3 scribed reference lines. Individual
      polyvinylsiloxane impressions were made (n = 10) for each of the specimens. The
      fabricated dies were measured (50x) to the nearest 0.0001 mm. Data were subject
      to ANOVA/Duncan tests at significance level 0.05 and pairwise comparisons.
      RESULTS: Type IV resin-impregnated dental stone and copper-plated dies most
      closely approximated the dimensions of the master die, and were not significantly
      different from each other in any of the pairwise comparisons. Conventional Types
      IV and V dental stone dies exhibited setting expansion within the range
      appropriate for gypsum. Epoxy resin die materials demonstrated shrinkage
      comparable to the expansion of the Types IV and V dies. Polyurethane dies
      displayed a combination of linear expansion and shrinkage. Bis-acryl composite
      resin dies had excessive shrinkage. CONCLUSIONS: Type IV resin-impregnated dental
      stone and copper-plated dies were more dimensionally accurate than the other die
      materials tested.

PMID- 15733133
TI  - Implant-supported facial prostheses provided by a maxillofacial unit in a U.K.
      regional hospital: longevity and patient opinions.
AB  - PURPOSE: The aim of this study was to acquire information on the types and
      longevity of implant-retained facial prostheses and the opinions of patients on
      several factors related to their prostheses. MATERIALS AND METHODS: A survey of
      75 maxillofacial prosthetic patients currently under treatment and review at the
      Maxillofacial Unit, Morriston Regional Hospital was conducted through a 23
      question postal questionnaire. These patients were selected as representative of
      a group of individuals receiving treatment or under review for the fabrication of
      maxillofacial prostheses. RESULTS: Of the prosthetic replacements, 83% were ear
      prostheses, 8% nose, 6% eye, and 2% combination prostheses. Of the 47
      respondents, 8 (17%) reported that they were currently wearing their original
      prostheses. The remaining 39 (83%) respondents had all been provided with at
      least 1 replacement prosthesis. The mean lifetime of the prostheses was found to
      be 14 months (range: 4-36 months). The majority of replacement prostheses in this
      study were provided as a result of color fade or wear of the silicone material of
      the previous prosthesis. Individuals with no previous experience wearing a
      prosthesis had an unrealistic expectation of their prosthesis longevity, with a
      mean value of 17.8 months. In comparison, individuals with previous experience
      had reduced expectations, with a mean of 14.4 months. In terms of the patients'
      opinions of the overall quality of their prostheses, the results demonstrated
      that a large number of patients were satisfied. Thirty-five patients rated their
      prostheses as excellent and 9 as good. At 7-12 months, 4 patients rated their
      prostheses as excellent and 8 as good. At 13 months, 4 patients rated their
      prostheses as excellent and 5 as good. CONCLUSIONS: It is important that advice
      be given to patients on the expected average longevity of their prostheses,
      together with information on factors affecting the longevity (i.e., environmental
      staining, cosmetics, and cleaning regimes). In this study, 26% of the replacement
      prostheses were provided due to color fading of the original prosthesis. This
      highlights the need for continuing research in the development of materials used
      for the construction of facial prostheses with improved properties, and in
      particular, improved color stability.

PMID- 15733134
TI  - A clinical report and overview of scientific studies and clinical procedures
      conducted on the 3M ESPE Lava All-Ceramic System.
AB  - The Lava All-Ceramic System (3M ESPE Dental Products, St. Paul, MN) is a high
      strength zirconia system, which can be utilized to create all-ceramic crowns and
      fixed partial dentures (FPDs) for use in the anterior and posterior regions of
      the oral cavity. The following study offers an overview of previously conducted
      scientific studies and clinical procedures that feature the Lava All-Ceramic
      System as well as a more general overview of zirconia ceramics. A clinical report
      demonstrates the use of the Lava All-Ceramic System with the restoration of 2
      single crowns.

PMID- 15733135
TI  - Predoctoral implant education in U.S. dental schools.
AB  - PURPOSE: In 2002, a survey of American dental schools was conducted to determine
      the curricular structure, teaching philosophies, and materials used in
      predoctoral implant dentistry courses. MATERIALS AND METHODS: The questionnaire
      was mailed to the predoctoral implant dentistry director/chairperson of 54 U.S.
      dental schools. Of these, 38 schools returned the completed survey resulting in a
      response rate of 70%. RESULTS: Eighty-four percent of the respondents indicated
      that an implant dentistry course is part of their school's requirements. Seventy
      percent indicated that this course is offered by either the Restorative or
      Prosthodontics Department in the third year of the predoctoral dental curriculum.
      For 75% of the schools, the duration of the course ranged from 3 to 6 months
      (mean of 5.5 months), 57% reported offering between 11 and 20 lecture hours (mean
      of 20.4 hours), and less than half of the schools (41%) have prosthodontists
      teaching the predoctoral implant dentistry course. In 78% of the schools, a
      laboratory course is offered in conjunction with the implant course. The majority
      of the schools (88%) allow predoctoral students to restore implant cases
      clinically. Seventy-three percent require some of the implant-related laboratory
      work to be completed by the students and the single-tooth implant restoration is
      the most popular type of implant restoration for 78% of the schools. CONCLUSIONS:
      Predoctoral implant dentistry educational programs vary from school to school,
      yet a large percentage of schools agree on certain topics.

PMID- 15733136
TI  - The history of articulators: "scribing" articulators--those with functionally
      generated custom guide controls, part II.

PMID- 15733137
TI  - The 30-second test for prosthodontists.

PMID- 15733143
TI  - Real-time polymerase chain reaction quantification of human cytomegalovirus and
      Epstein-Barr virus in periodontal pockets and the adjacent gingiva of
      periodontitis lesions.
AB  - BACKGROUND: Genomic sequences of human cytomegalovirus (HCMV) and Epstein-Barr
      virus (EBV), two herpesviruses, can frequently be detected in periodontal pockets
      of progressive periodontitis lesions, but the prevalence and load of the two
      viruses in gingival tissue are unknown. This study determined levels of HCMV and
      EBV DNA in the periodontal pocket and in the adjacent gingiva of periodontitis
      lesions using a real-time polymerase chain reaction (PCR) assay. MATERIAL AND
      METHODS: A total of 20 systemically healthy periodontitis patients participated
      in the study. Nine patients below 35 years of age were tentatively diagnosed as
      having aggressive (early onset) periodontitis, and 11 patients 36-56 years of age
      as having chronic (adult) periodontitis. Clinical parameters were evaluated using
      established methods. Using periodontal curettes, specimens were harvested from 6
      10 mm periodontal pockets and from the adjacent inflamed periodontal pocket wall.
      A 5'-nuclease (TaqMan) real-time PCR assay was used to identify and quantify
      genomic copies of periodontal HCMV and EBV. RESULTS: HCMV DNA was detected in 78%
      of subgingival and 33% of gingival tissue samples from aggressive periodontitis
      lesions, but only in 46% of subgingival and 9% of gingival tissue samples from
      chronic periodontitis lesions. In aggressive periodontitis, HCMV subgingival and
      gingival tissue counts were positively correlated with periodontal pocket depth
      and probing attachment loss at sample sites (p<or=0.03; Spearman's rank
      correlation coefficient test). EBV DNA was identified in 89% of subgingival and
      78% of gingival tissue samples from aggressive periodontitis lesions, but only in
      46% of both subgingival and gingival tissue samples from chronic periodontitis
      lesions. In aggressive periodontitis, positive correlations were found for EBV
      subgingival counts and periodontal pocket depth at sample sites (p=0.04;
      Spearman's correlation) and for EBV gingival tissue counts and whole mouth mean
      gingival index (p=0.04; Spearman's correlation). In chronic periodontitis,
      statistical significance was only found between EBV subgingival counts and
      periodontal pocket depth at sample sites (p=0.04; Spearman's correlation). HCMV
      EBV coinfection was revealed in 78% of aggressive periodontitis lesions but only
      27% of chronic periodontitis lesions (p=0.03; chi-squared test). Also, seven of
      nine aggressive periodontitis patients but only three of 11 chronic periodontitis
      patients revealed more than 10,000 copies of HCMV or EBV in subgingival or
      gingival tissue samples (p=0.03; chi-squared test). Four of six patients having
      mean periodontal pocket depth at sample teeth (four study sites per tooth)>6 mm,
      but none of 14 patients having mean pocket depth at sample teeth<or=6 mm revealed
      more than 100,000 copies of HCMV or EBV in subgingival or gingival samples
      (p=0.001; chi-squared test). In periodontitis lesions demonstrating herpesviruses
      in paired subgingival and gingival tissue samples, the tissue samples showed the
      higher HCMV copy counts in three of four patients and the higher EBV copy counts
      in six of eight patients. CONCLUSIONS: The elevated occurrence of HCMV and EBV
      DNA copies in periodontal pockets and in the gingival tissue of aggressive
      periodontitis lesions relative to chronic periodontitis lesions, and the increase
      in herpesvirus counts with increasing severity of periodontitis lend substantial
      support to a periodontopathic role of the two viruses. Real-time PCR
      determination of herpesvirus DNA in periodontal sites may become a promising
      marker to monitor the course of destructive periodontal disease. Herpesviruses
      and bacteria, now mostly studied in isolation, may cooperate synergistically in
      the development of periodontitis, and should probably be considered as a
      pathogenetic consortium in future investigations of periodontal infections.

PMID- 15733144
TI  - Stimulation of growth of Porphyromonas gingivalis by cell extracts from
      Tannerella forsythia.
AB  - OBJECTIVE: In order to examine if Tannerella forsythia stimulates the growth of
      Porphyromonas gingivalis, an in vitro study was performed. BACKGROUND: P.
      gingivalis and T. forsythia are often isolated simultaneously from active
      periodontitis sites, indicating that these bacteria somewhat interact in the
      periodontal environment. We reported previously that mixed infection of P.
      gingivalis and T. forsythia synergistically induced lesion formation in a murine
      abscess model, and gingipains of P. gingivalis played an important role in this
      synergism. One of the possible mechanisms of this synergism is growth promotion
      by coinfection of the two bacteria. METHODS: Cell extracts of T. forsythia were
      added to the nutrition-decreased medium and the promotion of growth of P.
      gingivalis was examined. RESULTS: Sonicated extract of T. forsythia stimulated
      growth of P. gingivalis in nutrition-decreased medium in a dose-dependent manner.
      Proteins appeared to be the nature of growth-promoting factor, and the cell
      extract of T. forsythia had no stimulating effect on the growth of P. gingivalis
      strain devoid of gingipain activities. CONCLUSION: A product or a component of T.
      forsythia seemed to stimulate growth of P. gingivalis under nutrition-limited
      conditions. Gingipains are considered to play an important role in digestion or
      uptake of this growth-promoting factor. The interaction between T. forsythia and
      P. gingivalis in growth may be in part related with the synergistic virulence in
      a murine model.

PMID- 15733145
TI  - Modulation of extracellular matrix synthesis and alkaline phosphatase activity of
      periodontal ligament cells by mechanical stress.
AB  - BACKGROUND: Loss of occlusal function has been reported to induce atrophic
      changes in the periodontal ligament. It is likely that mechanical stress triggers
      the biological response of periodontal ligament. However, there have been few
      reports studying the correlation between mechanical stress of varying magnitude
      and periodontal ligament cell activities such as extracellular matrix (ECM)
      synthesis. OBJECTIVE: The objective of this study is to clarify the influence of
      the mechanical stress on changes in mRNA expression levels of type I collagen and
      decorin genes, as well as alkaline phosphatase (ALP) activity in response to
      mechanical stress of varying magnitude. METHODS: Bovine periodontal ligament
      cells were cultured on flexible-bottomed culture plates and placed on the BioFlex
      Loading Stations. Cells were elongated at 6 cycles/min (5 s on and 5 s off) at
      each of six levels of stretch (0.2, 1.0, 2.0, 3.0, 10, 18% increase in the
      surface area of the bottom) for 48 h. We measured mRNA expression levels of type
      I collagen and decorin genes using quantitative reverse transcription-polymerase
      chain reaction (RT-PCR), and ALP activity in periodontal ligament cell culture
      under cyclic mechanical stretching. RESULTS: Mechanical tensional stress of low
      magnitude induced the increase of both type I collagen and decorin mRNA
      expression without changing ALP activity in periodontal ligament cells.
      Mechanical tensional stress of high magnitude induced the increase of type I
      collagen and decorin mRNA expression while decreasing ALP activity. CONCLUSION:
      These results suggest that different magnitude of tensional force induces
      different responses from periodontal ligament cells, and that mechanical stress
      plays an important role in remodeling and functional regulation of periodontal
      ligament.

PMID- 15733146
TI  - Keratinocyte growth factor-1 expression in healthy and diseased human periodontal
      tissues.
AB  - OBJECTIVES: Keratinocyte growth factor-1 (KGF-1) is up-regulated in chronic
      inflammation and specifically stimulates epithelial cell proliferation by
      signaling through the epithelial-specific keratinocyte growth factor receptor
      (KGFR). We examined KGF-1 and KGFR protein and gene expression in healthy and
      diseased periodontal tissues. METHODS: Tissues were collected from patients with
      periodontal health or disease, immediately frozen and stained for KGF-1 and KGFR
      protein expression. Laser capture microdissection of epithelial and connective
      tissue cells with reverse transcription-polymerase chain reaction (RT-PCR)
      examined KGF-1 and KGFR gene expression profiles and enzymatic digestion with
      heparitinase, chondroitinase ABC or pre-treatment with suramin examined
      epithelial surface molecule interactions with KGF-1. RESULTS: In tissues
      collected from healthy patients, KGF-1 protein localized to areas of junctional
      and basal oral epithelial cells and was significantly increased in periodontal
      pocket epithelium (p<0.01) and in the oral epithelium (p<0.05) of disease
      associated tissues. KGFR localized to the junctional and the parabasal cells of
      oral epithelium, with the relative staining intensity being increased in disease
      associated pocket epithelium (p<0.05). Laser capture microdissection with RT-PCR
      confirmed KGF-1 and KGFR were specifically expressed by connective tissue and
      epithelium, respectively. KGF-1 localization to epithelial cells was largely
      eliminated by suramin pre-treatment, indicating interaction with the KGFR.
      CONCLUSIONS: KGF-1 and KGFR proteins are expressed in healthy periodontal tissues
      but significantly increased in diseased periodontal tissues. We hypothesize up
      regulation of KGF-1 and KGFR protein associated with disease regulates epithelial
      cell behavior associated with onset and progression of periodontal pocket
      formation.

PMID- 15733147
TI  - Evaluation of gingival blood flow by the use of laser Doppler flowmetry following
      periodontal surgery. A pilot study.
AB  - OBJECTIVES: The aim of this pilot study was to evaluate the applicability of
      laser Doppler flowmetry (LDF) in recording the gingival blood flow following
      periodontal surgery. MATERIAL AND METHODS: Five patients suffering from advanced
      chronic generalized periodontitis were included in the study. After completion of
      basic periodontal therapy, full-mouth plaque score, bleeding on probing, gingival
      recession and clinical attachment level were recorded. The upper anterior areas
      with a pocket probing depth of 6 mm or more were treated with an access flap. LDF
      recordings were performed in both the buccal and palatal aspect of the operated
      areas with the aid of an individual acrylic stent at the day of the surgery,
      prior to local anaesthesia, 3 min following anaesthesia, immediately after the
      operation and at days 1, 2, 3, 4, 7, 15, 30 and 60 following operation. RESULTS:
      Overall, the blood flow decreased immediately following anaesthesia and remained
      in lower values compared to baseline immediately following operation. The
      gingival blood flow presented an overall increase in comparison to baseline
      values until the 7th day following surgery at the buccal and palatal interdental
      sites, as well as at the alveolar mucosa sites. By the 15th day, as well as at
      the following observation periods of 30 and 60 days, the gingival blood flow
      values at the palatal and alveolar mucosa sites were very similar to baseline.
      Increased blood flow changes were observed at 30 and 60 days following operation
      at the buccal interdental sites. CONCLUSION: The results of the present pilot
      study suggest that the LDF might present clinical applicability in recording
      changes in gingival blood flow following periodontal surgery.

PMID- 15733149
TI  - The prevalence and pathogenic differences of Porphyromonas gingivalis fimA
      genotypes in patients with aggressive periodontitis.
AB  - BACKGROUND: The fimA gene, which encodes fimbrillin (FimA), is found in
      Porphyromonas gingivalis and has been classified into six genotypes based on
      nucleotide sequence. P. gingivalis that possesses the type II fimA gene is
      prevalent in adult periodontitis. OBJECTIVES: The aim of this study was to
      investigate the prevalence of P. gingivalis fimA genotypes in Japanese aggressive
      periodontitis patients, and to examine their virulence. METHODS: Subgingival
      plaque samples were obtained from 223 sites in 18 aggressive periodontitis
      patients and 95 sites in 22 periodontally healthy young adults. Actinobacillus
      actinomycetemcomitans, P. gingivalis and Tannerella forsythensis detection,
      determination of the fimA genotype in P. gingivalis, and the quantification of P.
      gingivalis were analyzed by polymerase chain reaction (PCR) methods. The
      proteolytic activities of the P. gingivalis fimA type I and fimA type II were
      also examined. RESULTS: In aggressive periodontitis patients, the most prevalent
      fimA genotype was the type II (46.7%), followed by the type Ib and type I,
      whereas in healthy subjects, the type I fimA was the only genotype detected. The
      number of P. gingivalis pathogens was the greatest in the type I fimA positive
      sites, and the frequency of coexisting A. actinomycetemcomitans and T.
      forsythensis was highest in the type II fimA positive sites in the aggressive
      periodontitis patients. Both the arginine-specific cysteine proteinase (Arg
      gingipain) and lysine-specific cysteine proteinase (Lys-gingipain) activity of
      the P. gingivalis fimA type I strain were significantly higher than those of the
      fimA type II strains. CONCLUSIONS: These results suggest that differences in
      virulence exist among different fimA genotypes. Coadherence with other pathogens
      in P. gingivalis fimA type II-associated aggressive periodontitis and
      quantitative increases in P. gingivalis in fimA type I-associated aggressive
      periodontitis are related to this virulence.

PMID- 15733148
TI  - Expression of CD13/aminopeptidase N on human gingival fibroblasts and up
      regulation upon stimulation with interleukin-4 and interleukin-13.
AB  - BACKGROUND AND OBJECTIVES: Aminopeptidase N (APN)/CD13 is a multifunctional
      ectoenzyme that is involved in anti-inflammatory reactions, control of immune
      reactions and differentiation of many cellular systems. Here, we hypothesized
      that CD13/APN would be expressed on human gingival fibroblasts (hGF) and would
      contribute to the regulation of immune responses in periodontal tissue. METHODS
      AND RESULTS: CD13/APN was expressed on hGF at the mRNA and protein levels as
      determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow
      cytometry, respectively. Enzymatic activities accompanying the expression were
      assessed by colorimetrical analysis using the synthetic substrate Leu-p
      nitroanilide. We examined the possible regulation of CD13/APN expression on hGF
      in response to T cell-derived cytokines. T helper (Th) 2 cell type cytokines such
      as interleukin-4 and interleukin-13, but not interleukin-2 or interleukin-15,
      preferentially increased the expression of proteins as well as the enzymatic
      activities of CD13/APN in a dose-dependent manner. Receptors for these cytokines,
      the interleukin-4 receptor alpha chain, interleukin-13 receptor alpha1 chain, and
      interleukin-2R common gamma chain, were expressed on hGF assessed by RT-PCR or
      flow cytometry. hGF exhibited inhibitory effects for formyl-methionyl-leucyl
      phenylalanine (FMLP)-induced polymorphonuclear leukocyte-activation that was
      evaluated by Mac-1 expression, and this inhibitory effect was partially recovered
      by pre-treatment with the APN-specific inhibitor bestatin. CONCLUSIONS: These
      findings suggested that CD13/APN expressed by hGF could contribute to the anti
      inflammatory response in periodontal tissue, and may be involved in disease
      processes mediated by Th2 cells.

PMID- 15733150
TI  - Parotid secretory protein is expressed and inducible in human gingival
      keratinocytes.
AB  - BACKGROUND: Parotid secretory protein (PSP) is a major salivary protein that is
      thought to possess both antibacterial and anti-inflammatory activity. A major
      question is whether PSP expression can be regulated by humoral factors and
      bacteria. Periodontitis is an inflammatory lesion initiated by interaction
      between gingival keratinocytes and periodontopathogenic microorganisms such as
      the Gram-negative anaerobe Porphyromonas gingivalis. Cytokines and sex hormones
      have been implicated in the progression of various forms of periodontal diseases.
      MATERIALS AND METHODS: We investigated the expression of PSP and its regulation
      in primary cultures of human gingival keratinocytes (HGK). HGK at the third or
      fourth passage were exposed to heat-killed P. gingivalis, tumor necrosis factor
      alpha (TNF-alpha) and 17beta-estradiol. The PSP mRNA levels were examined by real
      time polymerase chain reaction (PCR). The protein expression of PSP was confirmed
      by immunofluorescence. RESULTS: Heat-killed P. gingivalis, TNF-alpha and 17beta
      estradiol all resulted in increased HGK levels of mRNA for PSP as determined by
      real-time PCR analysis. Immunofluorescence demonstrated increased PSP localized
      within the cytoplasm of HGK following exposure to killed P. gingivalis.
      CONCLUSION: The present study has demonstrated for the first time that PSP is
      expressed in keratinocytes and that it can be up-regulated by bacteria and
      humoral factors. Thus PSP may have a role in the innate defense system at the
      gingival epithelial surface.

PMID- 15733151
TI  - Effects of enamel matrix proteins on tissue formation along the roots of human
      teeth.
AB  - OBJECTIVE: Enamel matrix-derived proteins (EMD) are thought to trigger the
      formation of acellular extrinsic fibre cementum (AEFC), while other reports
      indicate that EMD may have osteogenic potential. The aim of the present study was
      to characterize the tissues developing on the root surface following application
      of EMD. METHODS: Twelve human periodontitis-affected teeth, scheduled for
      extraction, were treated with EMD. Two to 6 weeks later, the teeth were
      extracted, demineralized and processed for embedding in acrylic and epoxy resins.
      New tissue formation was analysed by light and transmission electron microscopy.
      RESULTS: New tissue formation on the root was observed in the notch and on both
      scaled and unscaled root surfaces distant of the notch area in six defects. The
      newly formed tissues on the root were thick, collagenous, devoid of extrinsic
      fibres, and had an irregular surface contour. The presence of electron-dense,
      organic material in the collagenous matrix indicated at least partial
      mineralization. Embedded cells were numerous and the cells on the matrix surface
      were very large in size. Abundant rough endoplasmic reticulum and a prominent
      Golgi complex were evident. The presence of a split between the treated root
      surfaces and the newly formed tissue was a common observation, as was the
      presence of bacteria and host cells in the interfacial gap. CONCLUSION: Following
      treatment with EMD, a bone-like tissue resembling cellular intrinsic fibre
      cementum may develop on the root surfaces, instead of AEFC. Furthermore, EMD may
      both induce de novo formation of a mineralized connective tissue on scaled root
      surfaces and stimulate matrix deposition on old native cementum. Interfacial
      bonding appeared to be weak after 6 weeks of healing.

PMID- 15733152
TI  - Effectiveness of scaling and root planing versus modified Widman flap on nitric
      oxide synthase and arginase activity in patients with chronic periodontitis.
AB  - BACKGROUND: Nitric oxide (NO) is synthesized from the conversion of L-arginine to
      L-citrulline by NO synthase (NOS). Arginase, which is an arginine-depleting
      enzyme, can compete with NOS for the common substrate L-arginine and thus inhibit
      NO production. OBJECTIVES: In the present study, we aimed to examine the
      correlation between the arginase and NOS activity in patients with chronic
      periodontitis and to compare the effects of scaling and root planing and modified
      Widman flap procedures on enzyme activity. MATERIAL AND METHODS: The study
      included 13 patients diagnosed with chronic periodontitis. Using a split-mouth
      design, the defects showing>or=7 mm of attachment loss were treated either with
      scaling and root planing or with modified Widman flap. Gingival biopsies from
      both sites were obtained at baseline and 2 months after periodontal treatment.
      Immunohistochemical staining was performed for evaluating NOS expression and
      specific arginase activity was determined spectrophotometrically. RESULTS:
      Although inflamed periodontal tissues demonstrated a strong inducible NOS (iNOS)
      expression at baseline, immunostaining decreased after periodontal treatment.
      iNOS expression intensity and the number of inflammatory cells showing iNOS
      expression were found to be higher in the scaling and root planing group compared
      to the modified Widman flap group. The specific activity of arginase was measured
      as 0.18+/-0.07 IU/mg protein in the modified Widman flap group and 0.25+/-0.11
      IU/mg protein in the scaling and root planing group at baseline. After
      periodontal therapy, the enzyme level was increased to 0.68+/-0.14 IU/mg protein
      in the modified Widman flap and to 1.10+/-0.23 IU/mg protein in the scaling and
      root planing group. CONCLUSION: This study was the first report of evaluating the
      involvement of the arginine-NO pathway in chronic periodontitis and this might be
      considered to be of value in understanding the periodontal disease mechanisms.

PMID- 15733153
TI  - Regulation of extracellular signal-regulated protein kinase signaling in human
      osteosarcoma cells stimulated with nicotine.
AB  - BACKGROUND: Cigarette smoking is a major risk factor in the development and
      further progression of periodontal diseases. Currently, there is limited
      information on the regulation of mitogen-activated protein kinases (MAPK)
      expression in smoking-associated periodontal disease. OBJECTIVES: The aim of the
      present study was to investigate the effects of nicotine on the expression of
      MAPKs in human osteosarcoma cell line U2OS cells. Furthermore, various
      pharmacological agents were added to search the possible regulation mechanisms on
      nicotine-induced MAPKs expression. METHODS: Cytotoxicity and western blot assays
      were used to investigate the effects of U2OS cells exposed to nicotine. In
      addition, various pharmacological agents [NS-398, dexamethasome, 2
      oxothiazolidine-4-carboxylic acid (OTZ), herbimycin A, and curcumin] were added
      to test how they modulated the effects of nicotine-induced MAPKs expression.
      RESULTS: Concentrations of nicotine higher than 5 mm demonstrated cytotoxicity to
      U2OS cells (p<0.05). A nicotine concentration of 5 mm was found to induce
      extracellular signal-regulated kinase (ERK) phosphorylation in a time-dependent
      manner (p<0.05). In addition, amounts of ERK protein were unaffected by nicotine
      during the same time interval. By contrast, nicotine has no effect on either c
      Jun N-terminal kinase (JNK) or p38, respectively. In addition, NS-398,
      dexamethasone, OTZ, herbimycin A, and curcumin were found to inhibit the nicotine
      induced ERK expression (p<0.05). CONCLUSIONS: The activation of ERK expression by
      nicotine suggests a potential role for nicotine in the pathogenesis of cigarette
      smoking-associated periodontal disease. In addition, nicotine-induced ERK
      expression was down-regulated by NS-398, dexamethasone, OTZ, herbimycin A, and
      curcumin.

PMID- 15733154
TI  - Er:YAG laser irradiation increases prostaglandin E production via the induction
      of cyclooxygenase-2 mRNA in human gingival fibroblasts.
AB  - BACKGROUND AND OBJECTIVES: It has been reported that both prostaglandin E2 (PGE2)
      and Er:YAG laser irradiation accelerate wound healing. The stimulatory action of
      laser seems to occur during the proliferative stage of healing by stimulation of
      prostaglandin E2 and cyclooxygenase-2 (COX-2), which are crucial early mediators
      in the natural healing process. We have then investigated the effect of Er:YAG
      laser irradiation on PGE2 production and COX-2 gene expression in human gingival
      fibroblast in vitro. MATERIAL AND METHODS: Cultured fibroblasts were exposed to
      low-power Er:YAG laser irradiation with an energy density of 3.37 J/cm2. The
      amount of PGE2 production was measured by enzyme-linked immunosorbent assay
      (ELISA). COX-2 mRNA level, which is a critical enzyme for PGE2 production, was
      analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:
      Er:YAG laser significantly increased PGE2 production by human gingival
      fibroblasts. COX-2 mRNA, which was hardly detectable in control, increased
      dramatically after irradiation. COX-2 inhibitor, NS398, completely inhibited the
      PGE2 synthesis stimulated by Er:YAG laser irradiation. CONCLUSION: Our results
      showed that Er:YAG laser irradiation appears to exert its stimulative action on
      gingival fibroblasts proliferation through the production of PGE2 via the
      expression of COX-2. This should be considered as one of the important regulatory
      pathways to accelerate wound healing after Er:YAG laser irradiation.

PMID- 15733155
TI  - Periodontitis lesions are a source of salivary cytomegalovirus and Epstein-Barr
      virus.
AB  - AIM: Several herpesvirus species can be detected in periodontal pockets and
      saliva. This study compared human cytomegalovirus (HCMV) and Epstein-Barr virus
      (EBV) DNA copy counts in periodontitis sites and in whole saliva, and evaluated
      the potential of periodontal therapy to reduce the salivary level of the two
      viruses. MATERIAL AND METHODS: A total of 20 systemically healthy periodontitis
      patients, 21-56 years of age, participated in the study. All 20 patients were
      examined at baseline, and seven patients also at 3 months after periodontal
      therapy. Treatment included oral hygiene instruction, scaling and root planing,
      and surgery. Clinical parameters were evaluated using established methods. In
      each patient, virological samples were collected from one periodontal pocket of 6
      10 mm probing depth, from the adjacent inflamed periodontal pocket wall, and from
      unstimulated whole saliva. Relationships between subgingival, gingival tissue and
      salivary herpesvirus counts were evaluated using Spearman's and Kendall's rank
      correlation coefficient tests. The 5'-nuclease (TaqMan) real-time polymerase
      chain reaction (PCR) assay was employed to quantify genomic copies of periodontal
      HCMV and EBV. RESULTS: At baseline, the 20 periodontitis patients showed
      significant positive correlations between gingival tissue and salivary counts of
      HCMV DNA (p=0.003) and EBV DNA (p=0.045). Periodontal pocket depth was positively
      correlated with salivary EBV DNA counts (p=0.002). Periodontal therapy reduced
      average full-mouth periodontal pocket depth from 4.6 mm to 1.4 mm, plaque index
      from 2.1 to 0.9, and gingival index from 2.1 to 0.4. Following treatment, HCMV
      DNA counts decreased 37.5 fold in subgingival sites and 64.6 fold in saliva, and
      EBV DNA counts decreased 5.7 fold in subgingival sites and 12.9 fold in saliva.
      CONCLUSIONS: The present study provides compelling evidence of a periodontitis
      source for salivary HCMV and EBV. The potential of periodontal therapy to
      decrease herpesvirus salivary counts may help diminish herpesvirus transmission
      from person to person and herpesvirus-related diseases in exposed individuals.
      Further research is warranted to determine the relationship between periodontal
      herpesvirus counts and the risk of viral transmission to close acquaintances.

PMID- 15733156
TI  - How to choose tomorrow's doctors.

PMID- 15733157
TI  - Education in the genetics era: genetics education for health professionals--an
      essential component of genetics policy.

PMID- 15733158
TI  - Pilot evaluation of the World Federation for Medical Education's global standards
      for basic medical education.

PMID- 15733159
TI  - Implications of psychology-type theories for full curriculum interventions.

PMID- 15733160
TI  - Assessing suitability for a problem-based learning curriculum: evaluating a new
      student selection instrument.
AB  - CONTEXT: A new student selection instrument has been designed to assess candidate
      suitability for a problem-based learning, small group curriculum. OBJECTIVE: To
      evaluate the performance of the new teamwork selection instrument in terms of its
      discriminatory power, fairness, validity, reliability and acceptability among
      candidates. SAMPLE: A sample of 69 volunteer candidates attending for interview
      formed 13 teams of 5 or 6 candidates each. Each candidate was assessed
      independently by 2 assessors. Candidate performance in the exercise was used for
      instrument evaluation purposes only. RESULTS: The instrument demonstrated good
      item discrimination (item-total correlations r = between 0.75 and 0.83, P <0.01);
      the potential for good agreement between raters (63% agreement, weighted kappa =
      0.38, P <0.01); strong internal consistency reliability (Cronbach's alpha =
      0.93), and good acceptability among candidates. No sources of assessment bias
      were identified on the basis of candidates' age (univariate anova F = 0.43, P
      >0.05), gender (unrelated samples t-test F = 1.2, P >0.05) or socioeconomic
      background (univariate anova F = 0.85, P >0.05). There was no statistically
      significant relationship between the candidates' performance in the new exercise
      and their performance in the standardised formal interview (r = - 0.37, P >0.05);
      the instrument had limited predictive validity, and some of the measured
      attributes require conceptual clarification. Discussion Statistical and
      conceptual analysis highlights the scope for development in the teamwork
      exercise. The exercise appears to be well suited to assessing candidate
      suitability for a problem-based learning curriculum.

PMID- 15733161
TI  - Assessment of personal qualities in relation to admission to medical school.
AB  - BACKGROUND: Recently there has been much scrutiny of the medical school
      admissions process by universities, the General Medical Council and the public.
      Improved objectivity, fairness and effectiveness of selection procedures are
      desirable. The ultimate outcome sought is the graduation of competent doctors who
      reflect the values of and are in tune with the communities they serve. METHODS:
      Applicants to the Scottish medical schools sat a battery of psychometric tests to
      measure cognitive ability, personality traits and moral/ethical reasoning
      (Personal Qualities Assessment, PQA). Analysis determined the potential impact of
      the latter variables, and those of educational background and socioeconomic class
      (assessed by residential 'deprivation category'), upon success in gaining a place
      to study medicine. RESULTS: Cognitive ability did not vary significantly as a
      function of gender or educational background, although there was a trend for it
      to be lower in individuals from more deprived backgrounds. Women as a group were
      more empathic, with a greater communitarian orientation, than men. There was no
      significant difference between individuals attending independent and state-funded
      schools in respect of any of the qualities measured by the PQA. Applicants from
      deprived backgrounds and those attending state-funded schools would not be
      disadvantaged by an admissions process based on the PQA. CONCLUSION: The
      incorporation of an assessment tool such as the PQA may have positive
      implications for widening access and the objective selection of suitable medical
      students, resulting in the training of doctors who are more representative of the
      community at large. A longterm follow-up of the professional careers of those
      medical students who completed the PQA will be undertaken.

PMID- 15733162
TI  - Selection of medical students according to their moral orientation.
AB  - INTRODUCTION: Consideration has been given to the use of tests of moral reasoning
      in the selection procedure for medical students. We argue that moral orientation,
      rather than moral reasoning, might be more efficacious in minimising the
      likelihood of inappropriate ethical behaviour in medicine. A conceptualisation
      and measure of moral orientation are presented, together with findings from 11
      samples of medical school applicants and students. AIM: To provide empirical
      evidence for the reliability and validity of a measure of moral orientation and
      to explore gender, age, cultural and educational influences on moral orientation.
      METHODS: A questionnaire designed to measure a libertarian-dual-communitarian
      dimension of moral orientation was completed by 7864 medical school applicants
      and students in Australia, Israel, Fiji, New Zealand, Scotland and England and by
      84 Australian psychology students between 1997 and 2001. RESULTS: Older
      respondents produced marginally higher (more communitarian) moral orientation
      scores, as did women compared to men. Minor but significant (P <0.05) cultural
      differences were found. The Israeli samples produced higher mean moral
      orientation scores, while the Australian psychology student sample produced a
      lower (more libertarian) mean score relative to all other samples. No significant
      change in moral orientation score was observed after 1 year in a sample of
      Australian medical school students (n=59), although some differences observed
      between 5 cohorts of Australian medical students (Years 1-5; n=234) did reach
      significance. Moral orientation scores were found to be significantly correlated
      with a number of personality measures, providing evidence of construct validity.
      In all samples moral orientation significantly predicted the moral decisions made
      in response to the hypothetical dilemmas embedded in the measurement instrument.
      Discussion The results provide support for the conceptualisation of a libertarian
      dual-communitarian dimension of moral orientation and demonstrate the
      psychometric properties of the measurement instrument. A number of questions
      concerning the use of such tests in selection procedures are considered.

PMID- 15733163
TI  - Sources of validity evidence for an internal medicine student evaluation system:
      an evaluative study of assessment methods.
AB  - BACKGROUND: Medical students' final clinical grades in internal medicine are
      based on the results of multiple assessments that reflect not only the students'
      knowledge, but also their skills and attitudes. OBJECTIVE: To examine the sources
      of validity evidence for internal medicine final assessment results comprising
      scores from 3 evaluations and 2 examinations. METHODS: The final assessment
      scores of 8 cohorts of Year 4 medical students in a 6-year undergraduate
      programme were analysed. The final assessment scores consisted of scores in ward
      evaluations (WEs), preceptor evaluations (PREs), outpatient clinic evaluations
      (OPCs), general knowledge and problem-solving multiple-choice questions (MCQs),
      and objective structured clinical examinations (OSCEs). Sources of validity
      evidence examined were content, response process, internal structure,
      relationship to other variables, and consequences. RESULTS: The median
      generalisability coefficient of the OSCEs was 0.62. The internal consistency
      reliability of the MCQs was 0.84. Scores for OSCEs correlated well with WE, PRE
      and MCQ scores with observed (disattenuated) correlation of 0.36 (0.77), 0.33
      (0.71) and 0.48 (0.69), respectively. Scores for WEs and PREs correlated better
      with OSCE than MCQ scores. Sources of validity evidence including content,
      response process, internal structure and relationship to other variables were
      shown for most components. CONCLUSION: There is sufficient validity evidence to
      support the utilisation of various types of assessment scores for final clinical
      grades at the end of an internal medicine rotation. Validity evidence should be
      examined for any final student evaluation system in order to establish the
      meaningfulness of the student assessment scores.

PMID- 15733164
TI  - Assessment in the context of uncertainty: how many members are needed on the
      panel of reference of a script concordance test?
AB  - PURPOSE: The script concordance test (SCT) assesses clinical reasoning in the
      context of uncertainty. Because there is no single correct answer, scoring is
      based on a comparison of answers provided by examinees with those provided by
      members of a panel of reference made up of experienced practitioners. This study
      aims to determine how many members are needed on the panel to obtain reliable
      scores to compare against the scores of examinees. METHODS: A group of 80
      residents were tested on 73 items (Cronbach's alpha: 0.76). A total of 38 family
      doctors made up the pool of experienced practitioners, from which 1000 random
      panels of reference of increasing sizes (5, 10, 15, 20, 25 and 30) were generated
      with a resampling procedure. Residents' scores were computed for each panel
      sample. Units of analysis were means of residents' score, test reliability
      coefficient and correlation coefficient between scores obtained with a given
      panel of reference versus the scores obtained with the full panel of 38.
      Statistics were averaged across the 1000 samples for each panel size for the mean
      and test reliability computations, and across 100 samples for the correlation
      computation. RESULTS: For sample variability, there was a 3-fold increase in
      standard deviation of means between a sample panel size of 5 (SD=1.57) and a
      panel size of 30 (SD=0.50). For reliability, there was a large difference in
      precision between a panel size of 5 (0.62) and a panel size of 10 (0.70). When
      the panel size was over 20, the gain became negligible (0.74 for 20 and 0.76 for
      38). For correlation, the mean correlation coefficient values were 0.90 with 5
      panel members, 0.95 with 10 members and 0.98 with 20 members. CONCLUSION: Any
      number over 10 is associated with acceptable reliability and good correlation
      between the samples versus the full panel of 38. For high stake examinations,
      using a panel of 20 members is recommended. Recruiting more than 20 panel members
      shows only a marginal benefit in terms of psychometric properties.

PMID- 15733165
TI  - The development, validity and reliability of a multimodality objective structured
      clinical examination in psychiatry.
AB  - OBJECTIVES: To evaluate the development, validity and reliability of a
      multimodality objective structured clinical examination (OSCE) in undergraduate
      psychiatry, integrating interactive face-to-face and telephone history taking and
      communication skills stations, videotape mental state examinations and problem
      oriented written stations. METHODS: The development of the OSCE on a restricted
      budget is described. This study evaluates the validity and reliability of 4 15-18
      station OSCEs for 128 students over 1 year. Face and content validity were
      assessed by a panel of clinicians and from feedback from OSCE participants.
      Correlations with consultant clinical 'firm grades' were performed. Interrater
      reliability and internal consistency (interstation reliability) were assessed
      using generalisability theory. RESULTS: The OSCE was feasible to conduct and had
      a high level of high perceived face and content validity. Consultant firm grades
      correlated moderately with scores on interactive stations and poorly with written
      and video stations. Overall reliability was moderate to good, with G-coefficients
      in the range 0.55-0.68 for the 4 OSCEs. CONCLUSIONS: Integrating a range of
      modalities into an OSCE in psychiatry appears to represent a feasible, generally
      valid and reliable method of examination on a restricted budget. Different types
      of stations appear to have different advantages and disadvantages, supporting the
      integration of both interactive and written components into the OSCE format.

PMID- 15733166
TI  - Putting double marking to the test: a framework to assess if it is worth the
      trouble.
AB  - BACKGROUND: It is a challenge to assign a mark that accurately measures the
      quality of students' work in essay-type assessments that require an element of
      judgement and fairness by the markers. Double marking such assessments has been
      seen as a way of improving the reliability of the mark. The analysis approach
      often taken is to look for absolute agreement between markers instead of looking
      at all aspects of reliability. AIM: To develop an analytic process that will
      examine the components and meanings of reliability calculations that can be used
      for assessing the value of double marking a piece of work. METHODS: An
      undergraduate case study assessment in General Practice was used as an
      illustration. Datasets of double marking were collected retrospectively for 1999
      2000, and prospectively for 2002-03. An assessment of intermarker agreement and
      its effect on the reliability of the final mark for students was made, using
      methods dependent on the type of data collected and Generalisability Theory.
      RESULTS AND CONCLUSIONS: The data were used to illustrate how to interpret the
      results of Bland and Altman plots, anova tables and Cohen's kappa calculations.
      Generalisability Theory was used to show that, while there was reasonable
      agreement between markers, the reliability of the mark for the student was still
      only moderate, probably due to unexplained variability elsewhere in the process.
      Possible reasons for this variability are discussed. A flowchart of the decisions
      and actions needed to judge whether a piece of work should be double marked has
      been constructed.

PMID- 15733167
TI  - Assessing professional competence: from methods to programmes.
AB  - INTRODUCTION: We use a utility model to illustrate that, firstly, selecting an
      assessment method involves context-dependent compromises, and secondly, that
      assessment is not a measurement problem but an instructional design problem,
      comprising educational, implementation and resource aspects. In the model,
      assessment characteristics are differently weighted depending on the purpose and
      context of the assessment. EMPIRICAL AND THEORETICAL DEVELOPMENTS: Of the
      characteristics in the model, we focus on reliability, validity and educational
      impact and argue that they are not inherent qualities of any instrument.
      Reliability depends not on structuring or standardisation but on sampling. Key
      issues concerning validity are authenticity and integration of competencies.
      Assessment in medical education addresses complex competencies and thus requires
      quantitative and qualitative information from different sources as well as
      professional judgement. Adequate sampling across judges, instruments and contexts
      can ensure both validity and reliability. Despite recognition that assessment
      drives learning, this relationship has been little researched, possibly because
      of its strong context dependence. ASSESSMENT AS INSTRUCTIONAL DESIGN: When
      assessment should stimulate learning and requires adequate sampling, in authentic
      contexts, of the performance of complex competencies that cannot be broken down
      into simple parts, we need to make a shift from individual methods to an integral
      programme, intertwined with the education programme. Therefore, we need an
      instructional design perspective. IMPLICATIONS FOR DEVELOPMENT AND RESEARCH:
      Programmatic instructional design hinges on a careful description and motivation
      of choices, whose effectiveness should be measured against the intended outcomes.
      We should not evaluate individual methods, but provide evidence of the utility of
      the assessment programme as a whole.

PMID- 15733168
TI  - Perceptions of dissection by students in one medical school: beyond learning
      about anatomy. A qualitative study.
AB  - INTRODUCTION: The practice of dissection, as part of undergraduate medical
      education, has recently resurfaced in the public eye. This paper focuses on a
      number of important learning outcomes that were reported by Year 1-5 medical
      students in a British medical school, during the dissection sessions in the first
      2 years of their training, as part of a wider qualitative research project into
      undergraduate medical education. METHODS: A group of 29 students was selected by
      quota sampling, using the whole student population of the medical school as the
      sampling frame. Qualitative data were collected by 1 : 1 interviews with students
      and from formal non-participatory observations of dissection sessions. RESULTS:
      Apart from learning to cope with the overt 'emotional confrontation' with the
      cadavers which assists anatomical learning, 7 additional covert learning outcomes
      were identified by the students: teamwork, respect for the body, familiarisation
      of the body, application of practical skills, integration of theory and practice,
      preparation for clinical work, and appreciation of the status of dissection
      within the history of medicine. DISCUSSION: A number of medical schools have
      either removed the practical, hands-on aspect of dissection in the medical
      undergraduate curriculum or are seriously considering such a measure, on
      financial and/or human resource grounds. This study highlights the fact that
      dissection can impart anatomical knowledge as well as offer other relevant,
      positive learning opportunities to enhance the skills and attitudes of future
      doctors.

PMID- 15733169
TI  - Do students have sufficient knowledge of clinical anatomy?
AB  - INTRODUCTION: Comparisons of anatomy knowledge levels of students from various
      curricula show either no differences or small differences to the detriment of
      innovative schools. To pass judgement on the general level of students' anatomy
      knowledge, we need an absolute standard. The purpose of this study was to compare
      students' levels of anatomy knowledge as measured by a case-based anatomy test
      with standards set by different groups of experts. METHODS: A modified Angoff
      procedure was used to establish an absolute standard against which the students'
      results could be evaluated. Four panels of 9 anatomists, 7 clinicians, 9 recent
      graduates and 9 Year 4 students, respectively, judged 107 items of an anatomy
      test. The students' results on these items were compared with the standards
      obtained by the panels. RESULTS: If the standard established by the panel of Year
      4 students was used, 64% of the students would fail the test. The standards
      established by the anatomists, clinicians and recent graduates would yield
      failure rates of 42%, 58% and 26%, respectively. CONCLUSION: According to the
      panels' standards, many students did not know enough about anatomy. The high
      expectations that the Year 4 students appeared to have of their peers may
      contribute to students' uncertainty about their level of anatomy knowledge.

PMID- 15733170
TI  - Avoidable breaches of confidentiality: a study among students of medicine and of
      law.
AB  - OBJECTIVES: Avoidable breaches of patient confidentiality due to inadvertence or
      ignorance occur frequently. The aim of this study was to explore whether
      participants were able to identify violations of confidentiality and how serious
      these violations were. DESIGN: After a 2-hour theoretical education session,
      participants filled out a standardised questionnaire presenting 6 hypothetical
      cases (e.g. politician's illness mentioned to the doctor's family, violence
      inflicted by the police mentioned to a lawyer at a dinner party, both without
      patient consent) and asking whether confidentiality had been violated. Answers
      were given on a score of 0-3, where 0 = no violation and 3=serious violation.
      SETTING: University of Geneva, Switzerland. PARTICIPANTS: Three professors of
      criminal law (representing the gold standard) and convenience samples of 311 law,
      medical and dental students took part. Main outcome measures Students' answers
      were compared to the gold standard (answers of criminal law professors). RESULTS:
      According to our gold standard, a violation of confidentiality took place in all
      6 cases (scores: 3, 2, 3, 2, 3, 3; means of students: 1.7, 0.6, 1.0, 0.4, 1.5,
      2.6). Most students (88%) mistakenly believed in 1-3 cases that no violation took
      place. In only 2 cases did more than 90% of participants recognise the violation.
      Law students attributed significantly lower scores than medical or dental
      students in 3 cases and higher scores in 1 case. CONCLUSIONS: Despite theoretical
      education, participants did not fully understand obligations towards patient
      confidentiality when it came to practical situations, especially when colleagues
      and authorities (police, those in a judicial context) asked for information.
      Teaching should address the risk of patient identification and the seriousness of
      violations in order to motivate doctors to avoid unjustified violations of
      confidentiality.

PMID- 15733171
TI  - Discursive psychology as a qualitative approach for analysing interaction in
      medical settings.
AB  - PURPOSE: To introduce some features of the perspective of discursive psychology
      that may be useful for studying interaction in a range of medical settings.
      OVERVIEW: Discursive psychology considers the way psychological words and
      displays play a practical part in the activities that are performed in particular
      settings. It offers a way of understanding the role of psychological issues that
      is distinct from, and is sometimes obscured by, traditional social cognitive
      approaches. The approach is illustrated by the example of crying on a child
      protection helpline. The way crying is built from different elements, the way
      these elements are organised, and the way they are receipted are all highlighted.
      Crying is both performing and potentially disrupting actions. The virtues of high
      quality transcription, and of understanding the way crying is situated in the
      turn organisations of conversation, are demonstrated. EVALUATION: Discursive
      psychology involves particular ways of considering reliability and validity. The
      broader potential for such an approach in medical settings is discussed.

PMID- 15733172
TI  - The contribution of the social sciences to academic medicine.

PMID- 15733173
TI  - Should plastic surgery experience be an integral part of orthopaedic and trauma
      surgical training?

PMID- 15733174
TI  - The zen of lead extraction: obtaining the inner piece.

PMID- 15733175
TI  - Laser lead extraction: is there a learning curve?
AB  - Laser extraction of device leads offers an attractive alternative to
      countertraction and electrosurgical dissection sheath, potentially increasing
      efficacy and reducing complications. Wider adoption of this technology depends on
      relative ease of use. We report the experience of a new center to define the
      "learning curve." We performed 76 laser lead extractions in 75 patients (age 63
      +/- 17 years, 59 male) from July 2001 to January 2004. Two experienced device
      implanters who were novice extractors underwent a 2-day site visit to a high
      volume extraction center for training. Lead extractions were performed in the
      operating room with immediate surgical backup. The indication for extraction was
      infection in 39 (systemic in 15), erosion or pain in 11, and lead related or
      debulking in 25. Complete removal was achieved in 139 of 145 leads (14 ICD, 131
      pacemaker). Partial removal (<4 cm retained) was achieved in five leads (4%), and
      one lead could not be extracted. Complete success was 95% in the first third of
      patients, 94% in the second third, and 100% in the latter third. Fluoroscopy time
      fell from 19 +/- 22 minute in the first third of patients to 11 +/- 8 minute in
      the second third to 8 +/- 4 minute in the latter third (ANOVA P = 0.02). No major
      complications occurred. Local bleeding required minor left subclavian vein repair
      in two individuals. Symptomatic venous thrombosis occurred in 3 of the first 11
      cases 1-21 days after extraction, but did not occur in the next 64 consecutive
      patients who received a 1-month anticoagulation regimen (27% vs 0%, P < 0.001).
      One patient developed venous thrombosis 3 weeks following cessation of warfarin
      therapy. Practice guidelines reasonably recommend appropriate training prior to
      independent performance of lead extraction. The current study suggests that
      experienced device implanters with appropriate operative backup taking a limited,
      but intensive training program can be safe and effective at lead extraction in a
      short time, in part a reflection of the improved technology.

PMID- 15733176
TI  - Beyond coronary sinus angiography: the value of coronary arteriography and
      identification of the pericardiophrenic vein during left ventricular lead
      placement.
AB  - OBJECTIVE: The purpose of this study was to define the role coronary
      arteriography (venous phase) for improving the success of left ventricular (LV)
      lead implantation and to define the value of identifying the pericardiophrenic
      vein for optimal LV lead placement in biventricular (bi-v) device implantation.
      METHODS: Seventy-seven patients underwent bi-v device implantation between July
      2002 and October 2003. If the coronary sinus (CS) could not be accessed, then
      left coronary arteriography was performed during the same procedure. CS access
      was guided by venous phase images of the coronary arteriogram. The
      pericardiophrenic vein was identified by selective cannulation or direct
      visualization. Patients with Cr > 1.5 had gadolinium used as the contrast agent.
      RESULTS: Seventy-five successful implants were performed (97%). In seven patients
      (9%) repeated attempts at retrograde cannulation of the CS failed (attempt time
      130 +/- 20 minute, mean +/- SD). In these patients, coronary arteriography helped
      define the location of the CS, which was subsequently successfully cannulated. In
      six patients the pericardiophrenic vein was identified either during occlusion
      venography of the CS (postthoracotomy, veno-venous collaterals, n = 2) or during
      selective cannulation of the pericardiophrenic vein (using a DAIG Csl catheter, n
      = 4). The vein was directly visualized in three patients who underwent surgical
      LV lead implantation. LV leads in all these cases were implanted in areas not
      overlying the preidentified pericardiophrenic vein. During follow-up, none of
      these patients had evidence of phrenic nerve stimulation. CONCLUSIONS:
      Intraoperative left coronary arteriography increases the success of CS
      cannulation. Identification of the pericardiophrenic vein is a useful method to
      avoid phrenic nerve stimulation.

PMID- 15733177
TI  - The impact of supraventricular tachycardias on driving ability in patients
      referred for radiofrequency catheter ablation.
AB  - AIM: The aim of the present study was to evaluate the occurrence of arrhythmia
      related symptoms in patients with supraventricular tachycardia (SVT) referred for
      radiofrequency catheter ablation (RF ablation) with special focus on driving
      ability. METHODS AND RESULTS: Of the 301 patients referred for RF ablation
      between November 1998 and December 2000 due to SVT 226 were active drivers. The
      present study is an interview study with structured questions. Hemodynamic
      symptoms were frequently encountered during tachycardia. The symptoms occurred
      irrespective of driving. In the 226 active drivers, fatigue was reported in 77%,
      dizziness in 47%, breaking into a cold sweat in 52%, near-syncope in 50%, and
      syncope in 14%. Women experienced all symptoms more frequently than men: fatigue
      (P < 0.05), dizziness (P < 0.01), cold sweat (P < 0.05), near-syncope (P <
      0.001), and syncope (P < 0.01). Fifty-seven percent of the patients had
      experienced tachycardia while driving, and 42% of those patients had to stop
      because of it. Twenty-four of all patients considered their tachycardia as an
      obstacle to driving. There was a significant correlation (P < 0.001) between
      having experienced near-syncope and considering the risk for tachycardia as an
      obstacle. CONCLUSIONS: SVT frequently occurs during driving and is often
      associated with hemodynamic symptoms including near-syncope and syncope. Women
      reported tachycardia-related hemodynamic symptoms more often than men. There is a
      correlation between having experienced near-syncope and considering tachycardia
      as an obstacle to driving. The risk for serious tachycardia-related symptoms
      should be considered, especially in occupational drivers.

PMID- 15733178
TI  - Moderate exercise induces different autonomic modulations of sinus and AV node.
AB  - BACKGROUND: The routine determination of heart rate variability (HRV) from
      surface ECGs is based on RR intervals because of the difficulty to precisely
      locate the P-wave fiducial point on surface ECG recordings. The aim of the study
      was to assess the changes of RR, PP, and PR intervals at rest and during moderate
      exercise. The time intervals were determined from atrial and ventricular
      pacemaker-mediated intracardiac electrograms. METHODS: Ten patients in sinus
      rhythm with intrinsic AV node conduction who had received the dual-chamber
      pacemaker Logos (Biotronik) were included. High-resolution atrial and ventricular
      intracardiac electrograms were transmitted at rest in supine position and during
      walking to a portable external recorder. Recording sequences of 150 successive
      heart cycles were used for HRV analyses after computer-assisted triggering of P
      and R events. The HRV-index SDNN and power spectral densities for the low (LF;
      0.04-0.15 Hz) as well as high (HF; 0.15-0.40 Hz) frequency bands were determined.
      RESULTS: SDNN decreased from 26.0 +/- 8.1 ms at rest to 18.3 +/- 4.2 ms during
      exercise for the PP intervals (P < 0.05) and from 26.8 +/- 8.1 to 18.4 +/- 4.1 ms
      for the RR intervals (P < 0.05). The LF/HF ratio increased from 2.02 +/- 1.3 to
      4.5 +/- 1.5 in the atrium (P < 0.05) and from 2.0 +/- 1.2 to 5.2 +/- 1.9 in the
      ventricle P < 0.05). Comparing atrial and ventricular HRV at both activity
      levels, no significant differences were observed for the power of LF and HF
      spectral components. Regarding the PR intervals SDNN, the total power and the
      LF/HF ratio did not significantly change during exercise. CONCLUSIONS: The
      described technique enabled to record intracardiac electrograms not only at rest,
      but also during moderate exercise and to use them for HRV evaluation. The changes
      of PP and RR, but not of the PR intervals, during exercise indicate that
      autonomic inputs to the sinus node and AV node are independent from each other.
      The ventricular HRV seems to derive mainly from variations of the sinus node
      pulse formation.

PMID- 15733179
TI  - Effect of radiofrequency catheter ablation on plasma B-type natriuretic peptide.
AB  - The study was designed to investigate the impact of radiofrequency catheter
      ablation on the plasma level of B-type natriuretic peptide (BNP). In 36 patients
      who underwent catheter ablation of paroxysmal supraventricular tachycardia, the
      plasma level of BNP was analyzed before and after the ablation procedures. The
      plasma BNP at baseline, 30 minutes after the ablation, 3 and 24 hours after the
      ablation was 12.78 +/- 2.47, 18.45 +/- 4.02 (P = 0.446), 43.54 +/- 8.12 (P =
      0.0001), and 17.88 +/- 4.71 (P = 0.493) pg/mL, respectively. Plasma troponin I
      was also increased 3 and 24 hours after the ablation (n = 10, P < 0.05).
      Multivariate regression analysis showed a significant correlation between the
      levels of BNP 3 hours after ablation and the preablation BNP and the total
      radiofrequency energy used for the ablation. We conclude that radiofrequency
      catheter ablation of supraventricular tachycardia increases the plasma level of
      BNP. The clinical significance of the ablation-induced increase in BNP needs to
      be further investigated.

PMID- 15733180
TI  - Improved extraction of ePTFE and medical adhesive modified defibrillation leads
      from the coronary sinus and great cardiac vein.
AB  - BACKGROUND: Permanent leads with shocking coils for defibrillation therapy are
      sometimes implanted in the coronary sinus (CS) and great cardiac vein (GCV).
      These shocking coils, as documented by pathologic examination of animal
      investigations, often become tightly encapsulated by fibrosis and can be very
      difficult to remove. METHODS: One of three configurations of the Guidant model
      7109 Perimeter coronary sinus shocking lead was implanted into the distal portion
      of the GCV of 24 sheep for up to 14 months. Group 1 had unmodified coils
      (control), group 2 had coils backfilled with medical adhesive (MA), and Group 3
      had coils coated with expanded polytetrafluoroethylene (ePTFE). Eighteen leads,
      three from each group at 6 and 14 months were transvenously extracted from the
      left jugular vein. The remaining six animals were not subject to extraction. All
      animals were euthanized for pathological and microscopic examination. RESULTS:
      All six of the control, three of the MA, and one of the ePTFE leads required the
      use of an electrosurgical dissection sheath (EDS) for extraction. Five control,
      two MA, and none of the ePTFE leads had significant fibrotic attachments to the
      shocking coils. Significant trauma was observed at necropsy for those leads
      requiring the use of the EDS for extraction. CONCLUSIONS: Tissue ingrowth is a
      major impediment to the removal of defibrillation leads implanted in the CS and
      GCV of sheep. Reduction of tissue ingrowth by coating the shocking coils with
      ePTFE or by backfilling with MA facilitates transvenous lead removal with reduced
      tissue trauma.

PMID- 15733181
TI  - Beat-to-beat heart rate adaptation in pediatric and late adolescent patients with
      closed loop rate-responsive pacemakers.
AB  - The aim of this study was to evaluate the efficacy of physiological rate
      responsive pacemakers (Closed Loop Stimulation--CLS) to pace pediatric and late
      adolescent patients undergoing rest, mental, standing, and exercise testing. Dual
      chamber pacemaker is increasingly indicated for young patients. A new
      physiological pacing mode based on the indirect measure of ventricular
      contractility (CLS), has shown interesting results in adults, while no data on
      pediatric patients are available. RR intervals and beat-to-beat systolic and
      diastolic pressures were monitored in 12 pediatric patients (6 males, mean age 17
      years [12-22 years]) who had a transvenous implant of Inos2+-CLS dual-chamber
      pacemaker (Biotronik GmbH, Berlin, Germany) and endocardial leads. All the
      patients showed correct electrical parameters at the implant and during the
      follow-ups. Paced RR intervals decreased significantly (F = 7.28, P = 0.01) from
      0.85 +/- 0.08 seconds (rest) to 0.73 +/- 0.10 seconds (mental) and to 0.75 +/-
      0.010 seconds (standing); systolic/diastolic pressure was significantly higher (F
      = 12.2, P = 0.002/F = 13.6, P = 0.001) in mental (134.4 +/- 19.9/74.4 +/- 8.1
      mmHg) with respect to rest (115.1 +/- 18.3/61.0 +/- 6.1 mmHg), and standing
      (118.7 +/- 23.9/67.3 +/- 0.1 mmHg). During exercise the paced RR interval showed
      significant decrease of about 35% from baseline to maximum load (F = 24.90, P =
      0.001) and systolic pressure increased significantly (F = 4.91, P = 0.019) by
      about 34% from baseline to maximum load. The comparison between paced and
      spontaneous rates showed very similar values and trend. In addition, CLS mode
      does not seem to overrun the spontaneous heart activity, when present. This is a
      study to evaluate CLS pacing in pediatric and late adolescent patients. The study
      shows that CLS pacing responds to both physical and non-physical stressors,
      providing physiological pacing rates, as previously observed in adults.

PMID- 15733183
TI  - The earliest published electrocardiogram showing ventricular preexcitation.
AB  - When in 1930, Wolff, Parkinson, and White published what is today known as the
      WPW, or preexcitation syndrome, they, and subsequently others, found few
      comparable cases in the preceding literature. Among these the report of Cohn and
      Fraser, published in 1913, was the earliest. However, another even earlier
      documentation in a 1909 article by Hoffmann escaped notice till now. The ECG of a
      patient with paroxysmal tachycardia reveals a short PR interval and a delta-wave
      induced widening of the QRS complex, even though the reproduced tachycardia was
      not preexcitation related. The interpretation of this poorly reproduced ECG can
      be confirmed by another and more detailed description of the patient in an
      electrocardiography textbook published in 1914 by the same author. Thus, the
      earliest publication of an ECG showing ventricular preexcitation now can be dated
      back to 1909. Moreover, the Hoffmann monograph contains two additional examples
      of the WPW syndrome not noticed until now. All three cases published by Hoffmann
      had their first ECG recordings in 1912 or earlier.

PMID- 15733182
TI  - Effects of epinephrine on right ventricular monophasic action potentials in the
      LQT1 versus LQT2 form of long QT syndrome: preferential enhancement of
      "triangulation" in LQT1.
AB  - AIMS: To explore effects of epinephrine and phenylephrine on the behavior of
      right ventricular monophasic action potentials (MAPs) in symptomatic LQT1 and
      LQT2 patients. METHODS AND RESULTS: We recorded endocardial MAPs from right
      interventricular septum at baseline and during epinephrine and phenylephrine
      infusions in six symptomatic DNA-verified LQT1 (QTc 528 +/- 83) and five LQT2
      patients (QTc 527 +/- 72) and in five control patients (QTc 381 +/- 22). We
      measured MAP durations at 90% and at 50% levels of repolarization and their
      difference (MAP50 to MAP90, a measure of MAP morphologic "triangulation"), during
      atrial pacing to characterize rate dependence of MAPs and repolarization phase 3
      durations, respectively. Restitution kinetics were determined during
      atrioventricular sequential pacing, using the approach of empirical restitution
      rate. Epinephrine prolonged MAP50-to-MAP90 duration and increased the rate
      dependence of MAP90 duration and increased restitution rate in type LQT1, but not
      in LQT2 patients nor in control subjects. Phenylephrine did not change MAP
      behavior. During epinephrine administration, both LQT1 and LQT2 patients had a
      ratio of the restitution rate of MAP to diastolic interval >1.0 at short
      diastolic intervals. CONCLUSION: Symptomatic LQT1 patients with prolonged
      baseline QTc intervals showed beta-adrenergic-induced changes in MAPs
      (triangulation) known to be arrhythmogenic, thus giving insight to the difference
      in clinical triggers of life-threatening arrhythmias between LQT1- and LQT2
      affected individuals.

PMID- 15733184
TI  - Right ventricular outflow tract tachycardia and polymorphic ventricular
      tachycardia.

PMID- 15733185
TI  - Sophisticated remote implantable cardioverter-defibrillator follow-up: a status
      report.

PMID- 15733186
TI  - Horses also deserve our respect and love.

PMID- 15733187
TI  - Nonsurgical management of cardiac tamponade caused by a temporary pacemaker lead.
AB  - Right ventricular perforation secondary to temporary pacemaker lead, resulting in
      cardiac tamponade, is a rare but life-threatening complication. Surgery is
      usually the definitive management described for such cases. We describe
      successful sealing of such a perforation by percutaneous instillation of
      cyanoacrylate glue, through a guiding catheter in the pericardial sac at the
      perforation site.

PMID- 15733188
TI  - The presence of epsilon waves in a patient with acute right ventricular
      infarction.
AB  - Epsilon wave is an unusual electrocardiographical finding, which may appear in
      other pathological conditions besides the arrhythmogenic right ventricular
      dysplasia, particularly in the acute myocardial infarction of the right
      ventricle, the inferior, or the posterior wall of the left ventricle. Its real
      incidence in these acute coronary syndromes remains unknown and will be probably
      difficult to assert, since it may be unnoticed by inexperienced physicians
      because of its little voltage. The outstanding interest of this case lies in the
      clear electrocardiographical images and in the step-by-step differential
      diagnosis discussed by the authors.

PMID- 15733189
TI  - Periodic limb movement disorder: an unusual mechanism of twiddling and potential
      benefit from cardiac resynchronization therapy.
AB  - Dislodgement of an LV lead is attributed to periodic limb movement disorder.
      Resynchronization therapy improves CHF and symptoms of periodic limb movement
      disorder. Potential interaction of disordered sleep and CHF in this case is
      briefly reviewed.

PMID- 15733190
TI  - Delayed lead perforation: a disturbing trend.
AB  - BACKGROUND: Delayed lead perforation (occurring more than 1 month after
      implantation) is a rare complication. Its pathophysiology and optimal management
      are currently unclear. METHODS: Three cases of delayed lead perforation (6-10
      month) were identified in patients with low-profile active fixation leads.
      RESULTS: All cases presented in a subacute fashion with pleuritic chest pain with
      confirmatory chest x-ray and device interrogation. Given the potential
      complications of a perforated lead, all cases had the lead extracted under TEE
      observation with cardiac surgery backup in the operating room. All patients
      tolerated extraction without complication. CONCLUSION: Based on these cases, we
      recommend a management scheme for patients who present with delayed lead
      perforation.

PMID- 15733191
TI  - A case of congenital junctional ectopic tachycardia: diagnosis and successful
      radiofrequency catheter ablation in infancy.
AB  - It is difficult to make a definitive diagnosis of congenital junctional ectopic
      tachycardia (JET) in utero. We report a case in which congenial JET was suspected
      by fetal M-mode echocardiography. Fetal M-mode tracing of the atria and ventricle
      clearly showed a gradual acceleration of ventricular activity at the beginning of
      tachycardia, the warming-up sign of ectopic tachycardia, which was followed by
      simultaneous contractions of atrium and ventricle. This report also describes
      successful emergent radiofrequency catheter ablation of congenital JET in infancy
      with preservation of normal AV nodal conduction for this patient.

PMID- 15733192
TI  - True right bundle branch block masking the typical ECG in Brugada syndrome.
AB  - A patient with a family history of sudden cardiac death and a structurally normal
      heart presented with a resting ECG intermittently displaying a saddle-type
      Brugada-ECG, which could be reproducibly converted to a coved-type ECG pattern
      suggestive of Brugada syndrome. However, no ST-segment changes occurred in the
      presence of a true right bundle branch block (RBBB) in the same patient. In
      consideration of the inalienable diagnostic criterion of dynamic ECG
      abnormalities in the right precordial leads in Brugada syndrome, setting the
      diagnosis in patients with true RBBB may be unattainable.

PMID- 15733194
TI  - Re: Interference between pacemaker and video capsule endoscopy.

PMID- 15733195
TI  - Knowing is half the battle: teaching stereotype threat as a means of improving
      women's math performance.
AB  - We tested whether informing women about stereotype threat is a useful
      intervention to improve their performance in a threatening testing situation. Men
      and women completed difficult math problems described either as a problem-solving
      task or as a math test. In a third (teaching-intervention) condition, the test
      was also described as a math test, but participants were additionally informed
      that stereotype threat could interfere with women's math performance. Results
      showed that women performed worse than men when the problems were described as a
      math test (and stereotype threat was not discussed), but did not differ from men
      in the problem-solving condition or in the condition in which they learned about
      stereotype threat. For women, attributing anxiety to gender stereotypes was
      associated with lower performance in the math-test condition but improved
      performance in the teaching-intervention condition. The results suggest that
      teaching about stereotype threat might offer a practical means of reducing its
      detrimental effects.

PMID- 15733196
TI  - The consequences of race for police officers' responses to criminal suspects.
AB  - The current work examined police officers' decisions to shoot Black and White
      criminal suspects in a computer simulation. Responses to the simulation revealed
      that upon initial exposure to the program, the officers were more likely to
      mistakenly shoot unarmed Black compared with unarmed White suspects. However,
      after extensive training with the program, in which the race of the suspect was
      unrelated to the presence of a weapon, the officers were able to eliminate this
      bias. These findings are discussed in terms of their implications for the
      elimination of racial biases and the training of police officers.

PMID- 15733197
TI  - Transmitting and decoding facial expressions.
AB  - This article examines the human face as a transmitter of expression signals and
      the brain as a decoder of these expression signals. If the face has evolved to
      optimize transmission of such signals, the basic facial expressions should have
      minimal overlap in their information. If the brain has evolved to optimize
      categorization of expressions, it should be efficient with the information
      available from the transmitter for the task. In this article, we characterize the
      information underlying the recognition of the six basic facial expression signals
      and evaluate how efficiently each expression is decoded by the underlying brain
      structures.

PMID- 15733198
TI  - Memory for fact, fiction, and misinformation: the Iraq War 2003.
AB  - Media coverage of the 2003 Iraq War frequently contained corrections and
      retractions of earlier information. For example, claims that Iraqi forces
      executed coalition prisoners of war after they surrendered were retracted the day
      after the claims were made. Similarly, tentative initial reports about the
      discovery of weapons of mass destruction were all later disconfirmed. We
      investigated the effects of these retractions and disconfirmations on people's
      memory for and beliefs about war-related events in two coalition countries
      (Australia and the United States) and one country that opposed the war (Germany).
      Participants were queried about (a) true events, (b) events initially presented
      as fact but subsequently retracted, and (c) fictional events. Participants in the
      United States did not show sensitivity to the correction of misinformation,
      whereas participants in Australia and Germany discounted corrected
      misinformation. Our results are consistent with previous findings in that the
      differences between samples reflect greater suspicion about the motives
      underlying the war among people in Australia and Germany than among people in the
      United States.

PMID- 15733199
TI  - Remembering a location makes the eyes curve away.
AB  - Working memory is a system that keeps limited information on-line for immediate
      access by cognitive processes. This type of active maintenance is important for
      everyday life activities. The present study shows that maintaining a location in
      spatial working memory affects the trajectories of saccadic eye movements toward
      visual targets, as the eyes deviate away from the remembered location. This
      finding provides direct evidence for a strong overlap between spatial working
      memory and the eye movement system. We argue that curvature is the result of the
      need to inhibit memory-based eye movement activity in the superior colliculus, in
      order to allow an accurate saccade to the visual target. Whereas previous
      research has shown that the eyes may deviate away from visually presented stimuli
      that need to be ignored, we show that the eyes also curve away from remembered
      stimuli.

PMID- 15733201
TI  - Effect of template complexity on visual search and dual-task performance.
AB  - Even dissimilar tasks interfere with one another when done together. We used
      visual search to examine the underlying cause of such interference. In many
      models, visual search is a process of biased competition controlled by a template
      describing the target to be sought. When the display is processed, matching
      against this template guides attention to the target. We show that increasing
      template complexity increased interference with a dissimilar concurrent task,
      story memory. This result was independent of reaction time: Increases in template
      complexity were associated with no increase in search time in Experiment 1 and
      with a decrease in search time in Experiment 2. The results show that the dual
      task demands of visual search reflect the complexity of the template used in task
      control, and that this factor can be isolated from other sources of difficulty.

PMID- 15733200
TI  - Beyond heritability: neurotransmitter genes differentially modulate visuospatial
      attention and working memory.
AB  - A cued, visuospatial attention task and a working memory task were administered
      to 89 healthy adults genotyped for a T-to-C polymorphism in CHRNA4, a nicotinic
      receptor subunit gene. Increasing gene dose of the C allele of the CHRNA4 gene
      (i.e., no C alleles, one C allele, two C alleles) was associated with increased
      reaction time (RT) benefits of valid attentional cuing and reduced RT costs of
      invalid cues, but was not associated with working memory performance. In a second
      experiment, 103 healthy persons were genotyped for a G-to-A polymorphism of the
      dopamine beta-hydroxylase (DBH) gene. Increasing gene dose of the G allele of the
      DBH gene was associated with increased working memory accuracy at a high memory
      load. However, there was no consistent association between the DBH gene and
      visuospatial attention. Thus, a double dissociation was observed, with
      visuospatial attention associated with CHRNA4 but not the DBH gene and,
      conversely, working memory associated with the DBH gene but not CHRNA4. The
      results show that normal allelic variations in single neurotransmitter genes
      modulate individual differences in processing components of cognitive functions
      in healthy individuals.

PMID- 15733202
TI  - Orientation congruency effects for familiar objects: coordinate transformations
      in object recognition.
AB  - How do observers recognize objects after spatial transformations? Recent
      neurocomputational models have proposed that object recognition is based on
      coordinate transformations that align memory and stimulus representations. If the
      recognition of a misoriented object is achieved by adjusting a coordinate system
      (or reference frame), then recognition should be facilitated when the object is
      preceded by a different object in the same orientation. In the two experiments
      reported here, two objects were presented in brief masked displays that were in
      close temporal contiguity; the objects were in either congruent or incongruent
      picture-plane orientations. Results showed that naming accuracy was higher for
      congruent than for incongruent orientations. The congruency effect was
      independent of superordinate category membership (Experiment 1) and was found for
      objects with different main axes of elongation (Experiment 2). The results
      indicate congruency effects for common familiar objects even when they have
      dissimilar shapes. These findings are compatible with models in which object
      recognition is achieved by an adjustment of a perceptual coordinate system.

PMID- 15733203
TI  - Preexisting knowledge versus on-line learning: what do young infants really know
      about spatial location?
AB  - Contemporary knowledge of infant cognition relies heavily on violation-of
      expectation experiments. However, there are two ways to conceptualize what occurs
      in such studies. Babies may react to anomalous test events because of preexisting
      world knowledge. Alternatively, they may react because they have learned about
      events during the familiarization period. One way to distinguish these
      possibilities is to contrast familiarization with everyday versus anomalous
      events. In the studies we report here, we used this method to probe the nature of
      5-month-olds' expectations about the locations of objects hidden in sand and
      later revealed. In Experiment 1, infants who initially saw everyday events did
      react to anomalous ones, as found previously, whereas infants who initially saw
      anomalous events did not react to everyday events. In Experiment 2, two
      alternative explanations of this pattern were ruled out. We conclude that by the
      age of 5 months, infants have expectations regarding the location of objects in
      continuous space.

PMID- 15733205
TI  - The look of love: gaze shifts and person perception.
AB  - Gaze direction is a vital communicative channel through which people transmit
      information to each other. By signaling the locus of social attention, gaze cues
      convey information about the relative importance of objects, including other
      people, in the environment. For the most part, this information is communicated
      via patterns of gaze direction, with gaze shifts signaling changes in the objects
      of attention. Noting the relevance of gaze cues in social cognition, we
      speculated that gaze shifts may modulate people's evaluations of others. We
      investigated this possibility by asking participants to judge the likability
      (Experiment 1) and physical attractiveness (Experiment 2) of targets displaying
      gaze shifts indicative of attentional engagement or disengagement with the
      participants. As expected, person evaluation was moderated by the direction of
      gaze shifts, but only when the judgment under consideration was relevant to
      participants. We consider how and when gaze shifts may modulate person perception
      and its associated behavioral products.

PMID- 15733204
TI  - Hearing what the eyes see: auditory encoding of visual temporal sequences.
AB  - When the senses deliver conflicting information, vision dominates spatial
      processing, and audition dominates temporal processing. We asked whether this
      sensory specialization results in cross-modal encoding of unisensory input into
      the task-appropriate modality. Specifically, we investigated whether visually
      portrayed temporal structure receives automatic, obligatory encoding in the
      auditory domain. In three experiments, observers judged whether the changes in
      two successive visual sequences followed the same or different rhythms. We
      assessed temporal representations by measuring the extent to which both task
      irrelevant auditory information and task-irrelevant visual information interfered
      with rhythm discrimination. Incongruent auditory information significantly
      disrupted task performance, particularly when presented during encoding; by
      contrast, varying the nature of the rhythm-depicting visual changes had minimal
      impact on performance. Evidently, the perceptual system automatically and
      obligatorily abstracts temporal structure from its visual form and represents
      this structure using an auditory code, resulting in the experience of "hearing
      visual rhythms."

PMID- 15733206
TI  - Victim derogation and victim enhancement as alternate routes to system
      justification.
AB  - Abstract-Numerous studies have documented the potential for victim-blaming
      attributions to justify the status quo. Recent work suggests that complementary,
      victim-enhancing stereotypes may also increase support for existing social
      arrangements. We seek to reconcile these seemingly contradictory findings by
      proposing that victim derogation and victim enhancement are alternate routes to
      system justification, with the preferred route depending on the perception of a
      causal link between trait and outcome. Derogating "losers" (and lionizing
      "winners") on traits (e.g., intelligence) that are causally related to outcomes
      (e.g., wealth vs. poverty) serves to increase system justification, as does
      compensating "losers" (and downgrading "winners") on traits (e.g., physical
      attractiveness) that are causally unrelated to those outcomes. We provide
      converging evidence using system-threat and stereotype-activation paradigms.

PMID- 15733207
TI  - Emotional and deliberative reactions to a public crisis: Mad Cow disease in
      France.
AB  - Although most theories of choice are cognitive, recent research has emphasized
      the role of emotions. We used a novel context--the Mad Cow crisis in France--to
      investigate how emotions alter choice even when consequences are held constant. A
      field study showed that individuals reduced beef consumption in months after many
      newspaper articles featured the emotional label "Mad Cow," but beef consumption
      was unaffected after articles featured scientific labels for the same disease.
      The reverse pattern held for the disease-related actions of a government
      bureaucracy. A lab study showed that the Mad Cow label induces people to make
      choices based solely on emotional reactions, whereas scientific labels induce
      people to consider their own probability judgments. Although the Mad Cow label
      produces less rational behavior than scientific labels, it is two to four times
      more common in the environment.

PMID- 15733208
TI  - Molecular modelling of drug targets: the past, the present and the future.
AB  - Most currently used therapeutic drugs have an enzyme or a membrane-bound receptor
      as site of action. The sequencing of the human and other genomes has provided a
      potential to identify many hitherto unknown proteins that might serve as new drug
      targets. To achieve this, knowledge about three-dimensional protein structures is
      crucial for the understanding of their functional mechanisms, and for a rational
      drug design. Over the last decade atomic resolution crystal structures of soluble
      proteins have been reported in a rapidly increasing number, but the detailed
      three-dimensional structures are still unknown for the majority of membrane
      proteins since their membrane association makes experimental structure
      determinations complicated. Computerized modelling of protein structures, based
      on experimentally determined structures of homologue proteins, may be a useful
      methodological alternative, especially for membrane proteins. In the past,
      molecular modelling of transporters and G-protein-coupled receptors was based on
      low-resolution structural data obtained by cryo-electron microscopy. Recent high
      resolution crystal structure determinations of a G-protein-coupled receptor,
      rhodopsin, and several different transporter proteins and ion channels have
      enabled construction of more accurate receptor and transporter models. For the
      future, collaborative structural genomics initiatives aim at determining the
      three-dimensional structure of all known proteins, based on a combination of
      experimental structure determination and molecular modelling. Development of
      still more powerful computer hardware and software will enable extensive studies
      of the protein structure and dynamics of new potential drug targets, but raises a
      new challenge in the validation and calibration of computerized methods of
      biosimulations.

PMID- 15733209
TI  - In silico predictions of drug solubility and permeability: two rate-limiting
      barriers to oral drug absorption.
AB  - Aqueous drug solubility and intestinal drug permeability are two of the most
      important factors influencing drug absorption. If the developability of a drug is
      to be included in the lead optimization, new experimental and computational
      models of solubility and permeability are needed. These models must have the
      capacity to handle a large amount of data. Nowadays, epithelial cell culture
      models such as Caco-2 are routinely used to assess intestinal drug permeability
      and transport in drug discovery settings. The permeability values obtained from
      the Caco-2 cell monolayers have been traditionally used to devise in silico
      models for the prediction of drug absorption. In this paper, the use of molecular
      surface areas as descriptors of permeability and solubility will be reviewed.
      Moreover, a virtual filter for the prediction of oral drug developability based
      on the successful combination of in vitro and in silico models of drug
      permeability and aqueous drug solubility will be discussed.

PMID- 15733210
TI  - Which in vitro screens guide the prediction of oral absorption and volume of
      distribution?
AB  - The development of medium to high-throughput in vitro screening of ADME
      (Absorption, Distribution, Metabolism, Excretion) properties has been the reply
      to higher demands on drug metabolism scientists to cope with progress in
      chemistry and biology. Two areas will be discussed here, namely screens for oral
      absorption and for volume of distribution. The prediction of these human
      pharmacokinetic parameters can be based on proper combination of simple
      physicochemical measurements. In the future in vitro screens most likely will be
      combined with in silico assessments of various ADME properties leading to the
      concept of in combo screening in drug discovery.

PMID- 15733211
TI  - Prediction of drug metabolism and interactions on the basis of in vitro
      investigations.
AB  - Drug metabolism profoundly affects drug action, because almost all drugs are
      metabolised in the body and thus their concentrations and elimination rates are
      dependent on metabolic activity. Drug metabolism contributes substantially to
      interindividual differences in drug response and is also often involved in drug
      interactions, resulting in either therapeutic failure or adverse effects.
      Knowledge about the metabolism of a new chemical entity and its affinity to drug
      metabolising enzymes helps in the drug development process by providing important
      information for the selection of a lead compound from among a number of
      substances pharmacologically equally effective in their therapeutic response. In
      drug development protocols, metabolism characteristics should be assessed very
      early during the development process. This has been made possible by the advances
      made especially in analytical capabilities and in in vitro technologies that are
      employed to predict in vivo metabolite profile, pharmacokinetic parameters and
      drug-drug interaction potential.

PMID- 15733212
TI  - The use of in vitro data in risk assessment.
AB  - Describing the toxicological profile of a substance is the first step required
      for risk assessment. Although a wide range of in vitro methods are widely used to
      characterise toxicological properties including toxicokinetics, regulatory
      acceptance is mainly confined to in vitro tests which investigate genotoxic end
      points. In vitro tests have been proposed for the endpoints acute toxicity,
      repeated dose toxicity and toxicity to reproduction which encompass the minimum
      requirements in the OECD SIDS programme. However, until now, limitations of the
      proposed tests preclude their application in a regulatory framework. Presently,
      in vitro tests play a major role in obtaining information on mechanism of
      toxicity with the perspective to be able to identify pathways of toxic responses
      by applying toxicogenomics techniques. Physiologically based toxicokinetic
      modelling is using data from in vitro studies to build up the model for a
      specific compound. Information from both areas is incorporated into the risk
      assessment to derive compound-specific safety factors, which account for species
      differences and for the variability among the human population, including
      possible sensitive subpopulations. Future developments to further enhance the use
      of in vitro methods in regulatory toxicology include the development of (Q)SAR
      approaches supplemented by mechanisms of toxicity, which can be addressed by
      developing methods of molecular toxicology.

PMID- 15733213
TI  - On the prediction of the human response: a recycled mechanistic
      pharmacokinetic/pharmacodynamic approach.
AB  - Although it is routine to predict the blood or plasma pharmacokinetics of
      compounds for man based upon preclinical studies, the real value of such
      predictions only comes when linked to drug effects. In the first example, the
      immunomodulator, FTY720, the first sphingosine-1-phosphate receptor agonist,
      stimulates the sequestration of lymphocytes into lymph nodes thus removing cells
      from blood circulation. A prior physiology-based pharmacokinetic model fitted the
      concentration-time course of FTY720 in rats. This was connected to an indirect
      response model of the lymphocyte system to characterise the cell trafficking
      effects. The IC(50) of FTY720 was different in the rat compared with the monkey;
      man was assumed to be similar to the monkey. The systemic lymphocyte half-lives
      were also different between species. To make predictions of the pharmacodynamic
      behaviour for man, two elements are required, i) systemic exposure, in this case
      from an upscaled physiology based model, and ii) an estimate of lymphocyte
      turnover in man, gained from the literature from other drug treatments.
      Predictions compared well with clinical results. The second example is the
      monoclonal antibody Xolair, designed to bind immunoglobulin E for atopic
      diseases. A mechanism based two-site binding model described the kinetics of both
      Xolair and endogenous IgE. This model has been reused for other monoclonal
      antibodies designed to bind fluid-phase ligands. Sensitivity analysis shows that
      if differences across species in the kinetics of the endogenous system are not
      accounted for, then pharmacokinetic/pharmacodynamic models may give misleading
      predictions of the time course and extent of the response.

PMID- 15733214
TI  - Application of full physiological models for pharmaceutical drug candidate
      selection and extrapolation of pharmacokinetics to man.
AB  - This paper describes how we are applying physiologically based models of
      pharmacokinetics as an integrated part in the research and preclinical
      development of novel drugs. The modeling and simulation tools and techniques used
      are briefly reviewed and the strategy for application in drug research is
      described. Three examples illustrate how such models may be applied at different
      stages ranging from early application prior to in vivo studies, through clinical
      candidate selection to the estimation of human kinetics and dose selection prior
      to clinical studies. Although there are obvious restrictions related to limited
      input data at the earlier stages, the examples illustrate some of the advantages
      of the approach compared to other more empirical methods. These advantages will
      be fully exploited with more widespread use of physiological models as powerful
      and user-friendly software make them accessible to non-specialists.

PMID- 15733215
TI  - Modeling and Monte Carlo simulations in oral drug absorption.
AB  - Drug dissolution, release and uptake are the principal components of oral drug
      absorption. All these processes take place in the complex milieu of the
      gastrointestinal tract and they are influenced by physiological (e.g. intestinal
      pH, transit time) and physicochemical factors (e.g. dose, particle size,
      solubility, permeability). Due to the enormous complexity issues involved, the
      models developed for drug dissolution and release attempt to capture their
      heterogeneous features. Hence, Monte Carlo simulations and population methods
      have been utilized since both dissolution and release processes are considered as
      time evolution of a population of drug molecules moving irreversibly from the
      solid state to the solution. Additionally, mathematical models have been proposed
      to determine the effect of the physicochemical properties, solubility/dose ratio
      and permeability on the extent of absorption for regulatory purposes, e.g.
      biopharmaceutics classification. The regulatory oriented approaches are based on
      the tube model of the intestinal lumen and apart from the drug's physicochemical
      properties, take into account the formulation parameters the dose and the
      particle size.

PMID- 15733217
TI  - Mechanism-based modeling of complex biomedical systems.
AB  - Mechanism-based modeling is an approach in which the physiological, pathological
      and pharmacological processes of relevance to a given problem are represented as
      directly as possible. This approach allows us (i) to test whether assumed
      hypotheses are consistent with observed behaviour, (ii) to examine the
      sensitivity of a system to parameter variation, (iii) to learn about processes
      not directly amenable to experimentation, and (iv) to predict system behavior
      under conditions not previously experienced. The paper illustrates different
      aspects of the application of mechanism-based modeling through three different
      examples of relevance to the treatment of diabetes and hypertension: subcutaneous
      absorption of insulin, pulsatile insulin secretion in normal young persons, and
      synchronization of the pressure and flow regulation in neighbouring nephrons. The
      underlying ideas are that each regulatory mechanism represents the target for
      intervention and that the development of new and more effective drugs must be
      based on a deeper understanding of the biological processes.

PMID- 15733216
TI  - Pharmacokinetic/pharmacodynamic modelling in oncological drug development.
AB  - For many oncological agents, myelosuppression is the dose-limiting toxicity and
      the quantitative characterisation of the relationship between drug dose, plasma
      concentration and haematological toxicity is of importance in the drug
      development. Mechanism-based population pharmacokinetic-pharmacodynamic models
      have been developed for this purpose and the applications of these in candidate
      selection, first-in-man studies, prodrug and formulation development, dose
      finding, schedule optimisation, assessing influence of modifying agents, drug
      combination studies, subgroup identification and feedback individualisation are
      reviewed.

PMID- 15733218
TI  - The odds that clinically unrecognized poor or partial adherence confuses
      population pharmacokinetic/pharmacodynamic analyses.
AB  - Electronic compilation of ambulatory patients' or trial participants' dosing
      histories has revealed that a wide range of dosing patterns, markedly skewed
      toward underdosing, occur in virtually every disease and treatment situation so
      far studied. In planning ambulatory trials and their analyses, one should
      recognize that patients' variable exposure to test drugs, created by their
      diversely erratic execution of protocol-specified dosing regimens, is generally
      the single largest source of variance in drug responses. Trial subjects' erratic
      dosing behaviour may, if ignored, weaken the trial's assay sensitivity. In
      contrast, reliably compiled and soundly analyzed dosing histories may greatly
      inform the analysis of the trial. Dosing histories found to be associated with
      suboptimal clinical results can highlight particular dosing patterns that should
      be avoided. Thus begins the sequence leading from first observations, to repeat
      observations, to ethically possible experimental designs, to causal inference,
      i.e., learning and then confirming. With the broadening use of electronic
      monitoring to estimate longitudinal drug exposure, the need exists for an
      explicit discipline that concerns itself with "what the patient does with the
      drug". It is called Pharmionics.

PMID- 15733219
TI  - Clinical trial simulation: a tool for understanding study failures and preventing
      them.
AB  - Execution models describe protocol deviations from a specified study design. When
      a clinical trial is planned, it is generally supposed that it will be executed
      according to a specific protocol that defines all aspects of the experimental
      design, from its beginning to its completion. Adherence to the protocol will
      allow estimation of the treatment outcome (safety and efficacy) with sufficient
      statistical power, or at least that is what is assumed. In reality, however,
      deviations from the protocol may lead to failure of the study to achieve its
      stated aims. In anticipation of protocol deviations that contribute to inflated
      residual variability and decreased study statistical power, trial designers tend
      to overpower studies in a rather arbitrary way. It is difficult to estimate
      quantitatively the consequences of one protocol deviation on statistical study
      power and, a fortiori, it is almost impossible to do it for a combination of
      protocol deviations. One way to study the consequences of model deviations is by
      using modelling and simulation techniques, and more specifically longitudinal
      stochastic models that can describe individual behaviours. Thus, execution models
      are powerful tools for identifying weaknesses or limitations in a proposed study
      design, which may be anticipated, avoided or resolved in order to increase
      robustness of the study design prior to implementation of the actual clinical
      study. As such, they are an integral component of clinical trial simulation and
      an essential tool in clinical trial design.

PMID- 15733220
TI  - Predicting the outcome of phase III trials using phase II data: a case study of
      clinical trial simulation in late stage drug development.
AB  - Maximizing the likelihood of success in Phase III is the ultimate goal of the use
      of modelling and simulation in the drug development process. The success in Phase
      III depends primarily on two questions: 1) Is the drug regimen actually
      efficacious and safe in the targeted patient population?, and 2) Will the planned
      Phase III clinical trial(s) be successful in demonstrating this? Traditionally,
      the first question is addressed in a qualitative, overall interpretation of
      available study results. Integrating this information into a formal statistical
      model of the action of the drug, allows running simulations to investigate the
      impact of uncertainties and imprecision in this knowledge. The second question is
      related to having an adequately designed clinical trial. Clinical trial
      simulation, using a drug action model, supplemented with appropriate models for
      disease progression and trial execution, allows assessing the impact of typical
      design features such as doses, sample size, in-/exclusion criteria, drop-out and
      trial duration on the trial outcome and thus optimising trial design. In this
      contribution, the use of modelling and simulation in the Phase II to Phase III
      transition is illustrated using real data of a drug for symptom relief in a
      chronic condition. A dose-response model of the clinical response was developed
      using data from Phase II. Simulations were performed to 1) generate the range of
      possible outcomes of ongoing Phase III trials and compare these to the blinded
      data being generated from these trials; 2) assess the robustness of the ongoing
      Phase III trials with respect to uncertainty of the true dose-response, patient
      variability in baseline severity and drug-response, and 3) assess the likelihood
      of achieving a clinically relevant response with a dose lower than those included
      in the trials.

PMID- 15733221
TI  - Internal exposure of children by simulated acute inhalation of volatile organic
      compounds: the influence of chemical properties on the child/adult concentration
      ratio.

PMID- 15733222
TI  - Model systems based on experimental animals for studies on drug metabolism in
      man: (mini)pig cytochromes P450 3A29 and 2E1.

PMID- 15733223
TI  - Pupil reaction: a valid sensitive clinical biomarker for 5-HT compounds.

PMID- 15733224
TI  - Low-dose methotrexate pharmacokinetics and pharmacodynamics in the therapy of
      severe psoriasis.

PMID- 15733225
TI  - Expression of MRP2 and MDR1 and other hepatic markers in hepatocytes in situ and
      WRL 68 cells in vitro.

PMID- 15733226
TI  - Predictive model for identifying potential CYP2D6 inhibitors.

PMID- 15733227
TI  - Evaluation of a physiologically-based pharmacokinetic approach for simulating the
      first-time-in-animal study.

PMID- 15733229
TI  - Non-standard correlations: in vitro in vivo correlations for immediate release
      products: comparison of different bioequivalence experiments.

PMID- 15733228
TI  - The effect of Mdr1 induction on the pharmacokinetics of rhodamine 123 in rats.

PMID- 15733230
TI  - Dissolution-bioequivalence non-correlations.

PMID- 15733231
TI  - A pharmacokinetic-pharmacodynamic model for predicting tumour growth inhibition
      in mice: a useful tool in oncology drug development.

PMID- 15733232
TI  - Optimizing drug regimens in cancer chemotherapy.

PMID- 15733233
TI  - Only connect?

PMID- 15733234
TI  - Assessing the value of environmental prevention programmes in reducing driving
      under the influence (DUI) among college students.

PMID- 15733235
TI  - The USA: alcohol and young people today.

PMID- 15733236
TI  - Conversation with George Vaillant.

PMID- 15733237
TI  - Recovery from DSM-IV alcohol dependence: United States, 2001-2002.
AB  - AIMS: To investigate the prevalence and correlates of recovery from Diagnostic
      and Statistical Manual version IV (DSM-IV) alcohol dependence by examining the
      past-year status of individuals who met the criteria for prior-to-past-year (PPY)
      dependence. DESIGN: Cross-sectional, retrospective survey of a nationally
      representative sample of US adults 18 years of age and over (first wave of a
      planned longitudinal survey). METHODS: This analysis is based on data from the
      2001-02 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC),
      in which data were collected in personal interviews conducted with one randomly
      selected adult in each sample household. A subset of the NESARC sample (total n =
      43 093), consisting of 4422 US adults 18 years of age and over classified with
      PPY DSM-IV alcohol dependence, were evaluated with respect to their past-year
      recovery status: past-year dependence, partial remission, full remission,
      asymptomatic risk drinking, abstinent recovery (AR) and non-abstinent recovery
      (NR). Correlates of past-year status were examined in bivariate analyses and
      using multivariate logistic regression models. FINDINGS: Of people classified
      with PPY alcohol dependence, 25.0% were still classified as dependent in the past
      year; 27.3% were classified as being in partial remission; 11.8% were
      asymptomatic risk drinkers who demonstrated a pattern of drinking that put them
      at risk of relapse; 17.7% were low-risk drinkers; and 18.2% were abstainers. Only
      25.5% of people with PPY dependence ever received treatment. Being married was
      associated positively with the odds of both AR and NR, and ethanol intake was
      negatively associated with both. Severity of dependence increased the odds of AR
      but decreased the odds of NR. The odds of AR (but not NR) increased with age and
      female gender but were decreased by the presence of a personality disorder.
      Treatment history modified the effects of college attendance/graduation, age at
      onset and interval since onset on the odds of recovery. CONCLUSIONS: There is a
      substantial level of recovery from alcohol dependence. Information on factors
      associated with recovery may be useful in targeting appropriate treatment
      modalities.

PMID- 15733238
TI  - Treatment and its correlates in the NESARC.

PMID- 15733239
TI  - Secrets and lies: comments on Dawson et al. (2005).

PMID- 15733240
TI  - Time to tear down the wall: comment on Dawson et al. (2005).

PMID- 15733241
TI  - Still difficult to know what alcohol dependent individuals can return to
      controlled drinking: comments on Dawson et al. (2005).

PMID- 15733243
TI  - Outcome criteria in smoking cessation trials: proposal for a common standard.
AB  - Smoking cessation treatment is now integrated into many health-care systems and a
      major research effort is under way to improve current success rates. Until now
      results from randomized clinical trials have been reported in many different
      ways, leading to problems of interpretation. We propose six standard criteria
      comprising the 'Russell Standard' (RS). These criteria are applicable to trials
      of cessation aids where participants have a defined target quit date and there is
      face-to-face contact with researchers or clinic staff, as follows. (1) Follow-up
      for 6 months (RS6) or 12 months (RS12) from the target quit date or the end of a
      predefined 'grace period'; (2) self-report of smoking abstinence over the whole
      follow-up period allowing up to five cigarettes in total; (3) biochemical
      verification of abstinence at least at the 6-month or 12-month follow-up point;
      (4) use of an 'intention-to-treat' approach in which data from all randomized
      smokers are included in the analysis unless they have died or moved to an
      untraceable address (participants who are included in the analysis are counted as
      smokers if their smoking status at the final follow-up cannot be determined); (5)
      following-up 'protocol violators' and using their true smoking status in the
      analysis; and (6) collecting follow-up data blind to smokers' allocation to trial
      group. We believe that these criteria provide the best compromise between
      practicability and surrogacy for long-term cessation and will enable meaningful
      comparison between studies. There may be good reasons why other outcome criteria
      would also be reported, and studies that involve interventions with special
      groups or where there is no designated target quit date or face to face contact
      would need to adapt these criteria accordingly.

PMID- 15733244
TI  - The role of the therapeutic alliance in the treatment of substance misuse: a
      critical review of the literature.
AB  - BACKGROUND: In the past two decades, a number of studies investigating the role
      of the therapeutic alliance in drug treatment have been published and it is
      timely that their findings are brought together in a comprehensive review. AIMS:
      This paper has two principal aims: (1) to assess the degree to which the
      relationship between drug user and counsellor predicts treatment outcome and (2)
      to examine critically the evidence on determinants of the quality of the
      alliance. METHODS: Peer-reviewed research located through the literature
      databases Medline, PsycInfo and Ovid Full Text Mental Health Journals using
      predefined search-terms and published in the past 20 years is considered. Further
      papers were identified from the bibliographies of relevant publications.
      FINDINGS: A key finding is that the early therapeutic alliance appears to be a
      consistent predictor of engagement and retention in drug treatment. With regard
      to other treatment outcomes, the early alliance appears to influence early
      improvements during treatment, but it is an inconsistent predictor of post
      treatment outcomes. There is relatively little research on the determinants of
      the alliance. In studies that are available, clients' demographic or diagnostic
      pre-treatment characteristics did not appear to predict the therapeutic alliance,
      whereas modest but consistent relationships were reported for motivation,
      treatment readiness and positive previous treatment experiences. CONCLUSIONS: The
      therapeutic alliance plays an important role in predicting drug treatment process
      outcomes, but too little is known about what determines the quality of the
      relationship between drug users and counsellors.

PMID- 15733245
TI  - Should nortriptyline be used as a first-line aid to help smokers quit? Results
      from a systematic review and meta-analysis.
AB  - OBJECTIVES: The objective of this paper is to evaluate the efficacy of
      nortriptyline for smoking cessation compared to placebo and bupropion sustained
      release. DATA SOURCES: Randomized trials were identified by (1) checking
      electronic and (2) online publicly accessible registers of clinical trials; (3)
      searching references of identified studies and screening abstract books of
      conferences and symposia, and (4) personal communication with the first authors
      of identified papers. REVIEW METHODS: We included randomized trials in which
      nortriptyline was compared to placebo or bupropion hydrochloride SR. The main
      clinical outcome measure was (at least) 6-month prolonged abstinence, confirmed
      with a biochemical test. To investigate the efficacy of nortriptyline in time, we
      calculated the percentage of smokers who relapsed in time. RESULTS: We identified
      five randomized trials, including 861 smokers. Compared to placebo medication,
      nortriptyline resulted in significantly higher prolonged abstinence rates after
      at least 6 months [relative risk (RR) = 2.4, 95% CI 1.7-3.6; RD = 0.11, 95% CI
      0.07-0.15]. The difference in efficacy between nortriptyline and placebo was
      highest in the first months after the target quit date. However, the number of
      people who remained abstinent decreased substantially and significantly faster
      over time in the nortriptyline group. Although bupropion resulted in higher
      abstinence rates compared with nortriptyline, the difference was not
      statistically significant (RR = 1.7, 95% CI 0.7-4.1). CONCLUSION: This systematic
      review and meta-analysis shows that the use of nortriptyline for smoking
      cessation resulted in higher prolonged abstinence rates after at least 6 months
      compared to placebo treatment. Furthermore, the use of nortriptyline for smoking
      cessation is well tolerated and safe. As a result, we believe health care
      professionals should be recommended to prescribe nortriptyline as a first-line
      therapy for smoking cessation, also because of the much lower cost of
      nortriptyline compared to bupropion SR.

PMID- 15733246
TI  - Reducing DUI among US college students: results of an environmental prevention
      trial.
AB  - AIMS: Driving under the influence (DUI) of alcohol is among the most common and
      serious alcohol-related problems experienced by US college students. Community
      based prevention trials using environmental approaches to DUI prevention have
      been effective in reducing DUI. Such interventions remain untested in college
      settings. This study is the first to test the efficacy of an environmental
      prevention campaign to reduce DUI among college students. DESIGN: We used a quasi
      experimental non-equivalent comparison group design to test the efficacy of the
      DUI prevention intervention. Students at the experimental university were exposed
      to a DUI prevention intervention that included a social marketing campaign, a
      media advocacy campaign and increased law enforcement (DUI checkpoints and roving
      DUI patrols). SETTING: Students from two large public universities located along
      the US/Mexico border participated in the seven-semester study. PARTICIPANTS: In
      total, 4832 college students took part. MEASURES: Using telephone interviews of
      randomly selected students, we took pre- and postintervention measures of self
      reported DUI. FINDINGS: Self-reported DUI (past year) decreased significantly
      from pre-test to post-test (odds ratio = 0.55) at the intervention school,
      whereas rates at the comparison campus remained stable. The campus-intervention
      interaction was statistically significant (P < 0.05), suggesting that the
      campaign led to the observed change in DUI. CONCLUSIONS: Environmental DUI
      campaigns similar to those validated in community prevention trials can be
      effective in college settings. Further research, however, is needed to determine
      the robustness of the changes associated with such campaigns.

PMID- 15733247
TI  - Preventing youth access to alcohol: outcomes from a multi-community time-series
      trial*.
AB  - AIMS/INTERVENTION: The Complying with the Minimum Drinking Age project (CMDA) is
      a community trial designed to test effects of two interventions designed to
      reduce alcohol sales to minors: (1) training for management of retail alcohol
      establishments and (2) enforcement checks of alcohol establishments. DESIGN: CMDA
      is a multi-community time-series quasi-experimental trial with a nested cohort
      design. SETTING/PARTICIPANTS: CMDA was implemented in 20 cities in four
      geographic areas in the US Midwest. MEASUREMENTS: The core outcome, propensity
      for alcohol sales to minors, was directly tested with research staff who
      attempted to purchase alcohol without showing age identification using a
      standardized protocol in 602 on-premise and 340 off-premise alcohol
      establishments. Data were collected every other week in all communities over 4
      years. Mixed-model regression and Box-Jenkins time-series analyses were used to
      assess short- and long-term establishment-specific and general community-level
      effects of the two interventions. FINDINGS: Effects of the training intervention
      were mixed. Specific deterrent effects were observed for enforcement checks, with
      an immediate 17% reduction in likelihood of sales to minors. These effects
      decayed entirely within 3 months in off-premise establishments and to an 8.2%
      reduction in on-premise establishments. CONCLUSIONS: Enforcement checks prevent
      alcohol sales to minors. At the intensity levels tested, enforcement primarily
      affected specific establishments checked, with limited diffusion to the whole
      community. Finally, most of the enforcement effect decayed within 3 months,
      suggesting that a regular schedule of enforcement is necessary to maintain
      deterrence.

PMID- 15733248
TI  - Associations between tobacco and cannabis use in remote indigenous populations in
      Northern Australia.
AB  - AIMS: To assess whether cannabis use, recently taken up by many indigenous
      Australians in remote communities, has reinforced tobacco use. DESIGN: Cross
      sectional study. SETTING: Three eastern Arnhem Land communities (Northern
      Territory, NT); total population = 3384, in 2001. PARTICIPANTS: From 1247 people
      aged 17-36 years, 190 (120 males, 70 females) were opportunistically recruited.
      MEASUREMENTS: Self-reported life-time and current tobacco, cannabis and other
      substance use were confirmed by local health workers and using clinic records.
      Participants reported level of substance use, frequency and duration (years
      used). Associations with tobacco use were calculated (odds ratios: OR) using
      logistic regression with age, sex, alcohol use and a history of petrol sniffing
      as confounders. FINDINGS: In univariate analyses current tobacco users were more
      likely than non-users to be using cannabis (OR = 3.1, 1.5-6.2, P = 0.002) and
      this association remained in multivariate analyses (OR = 3.0, 1.4-6.8, P =
      0.006). Tobacco use was associated with the number of years of cannabis use (P =
      0.035). The likelihood that tobacco users were also cannabis users increased as
      quantity of cannabis used increased (P = 0.008). Current tobacco use was no more
      likely in those who initiated cannabis from 1998 onwards than in those who
      initiated cannabis before 1998 (OR = 1.1, 0.4-3.2, P = 0.881). One-third of life
      time users of both tobacco and cannabis initiated their use at or near the same
      time, and very few of these (12%) had discontinued either cannabis or tobacco.
      CONCLUSIONS: Cannabis appears to have influenced the continued use of tobacco in
      these populations with possible additional burdens for cardiovascular and
      respiratory diseases and challenges for interventions.

PMID- 15733249
TI  - Tests of causal linkages between cannabis use and psychotic symptoms.
AB  - AIM: To examine possible causal linkages between cannabis use and psychosis using
      data gathered over the course of a 25-year longitudinal study. DESIGN: A 25-year
      longitudinal study of the health, development and adjustment of a birth cohort of
      1265 New Zealand children (635 males, 630 females). SETTING: The Christchurch
      Health and Development Study, a general community sample. PARTICIPANTS: A total
      of 1055 participants from the Christchurch Health and Development Study (CHDS)
      cohort for whom data on cannabis use and psychotic symptoms were available on at
      least one occasion from 18, 21 and 25 years. MEASUREMENTS: As part of this study,
      data were gathered on frequency of cannabis use and psychotic symptoms at ages
      18, 21 and 25 years. FINDINGS: Regression models adjusting for observed and non
      observed confounding suggested that daily users of cannabis had rates of
      psychotic symptoms that were between 1.6 and 1.8 times higher (P < 0.001) than
      non-users of cannabis. Structural equation modelling suggested that these
      associations reflected the effects of cannabis use on symptom levels rather than
      the effects of symptom levels on cannabis use. CONCLUSIONS: The results of the
      present study add to a growing body of evidence suggesting that regular cannabis
      use may increase risks of psychosis. The present study suggests that: (a) the
      association between cannabis use and psychotic symptoms is unlikely to be due to
      confounding factors; and (b) the direction of causality is from cannabis use to
      psychotic symptoms.

PMID- 15733250
TI  - Brief cognitive behavioural interventions for regular amphetamine users: a step
      in the right direction.
AB  - AIMS: The present study sought to replicate and extend a small pilot study
      conducted by Baker, Boggs & Lewin (2001) which demonstrated that brief
      interventions consisting of motivational interviewing and cognitive-behaviour
      therapy (CBT) were feasible and associated with better outcomes compared with a
      control condition. DESIGN: Randomized controlled trial (RCT). SETTING: Greater
      Brisbane Region of Queensland and Newcastle, NSW, Australia. PARTICIPANTS: The
      study was conducted among 214 regular amphetamine users. MEASUREMENTS:
      Demographic characteristics, past and present alcohol and other drug use and
      mental health, treatment, amphetamine-related harms and severity of dependence.
      FINDINGS: The main finding of this study was that there was a significant
      increase in the likelihood of abstinence from amphetamines among those receiving
      two or more treatment sessions. In addition, the number of treatment sessions
      attended had a significant short-term beneficial effect on level of depression.
      There were no intervention effects on any other variables (HIV risk-taking,
      crime, social functioning and health). Overall, there was a marked reduction in
      amphetamine use among this sample over time and, apart from abstinence rates and
      short-term effects on depression level, this was not differential by treatment
      group. Reduction in amphetamine use was accompanied by significant improvements
      in stage of change, benzodiazepine use, tobacco smoking, polydrug use, injecting
      risk-taking behaviour, criminal activity level, and psychiatric distress and
      depression level. CONCLUSIONS: A stepped-care approach is recommended. The first
      step in providing an effective intervention among many regular amphetamine users,
      particularly those attending non-treatment settings, may include provision of: a
      structured assessment of amphetamine use and related problems; self-help
      material; and regular monitoring of amphetamine use and related harms. Regular
      amphetamine users who present to treatment settings could be offered two sessions
      of CBT, while people with moderate to severe levels of depression may best be
      offered four sessions of CBT for amphetamine use from the outset, with further
      treatment for amphetamine use and/or depression depending on response.
      Pharmacotherapy and/or longer-term psychotherapy may be suitable for non
      responders. An RCT of a stepped-care approach among regular amphetamine users is
      suggested.

PMID- 15733251
TI  - Does parental smoking cessation encourage their young adult children to quit
      smoking? A prospective study.
AB  - AIMS: To investigate the extent to which parental early and late smoking
      cessation predicts their young adult children's smoking cessation. DESIGN:
      Parental early smoking cessation status was assessed when children were in 3rd
      grade, parental late smoking cessation was assessed when children were in 11th
      grade, and young adult children's smoking cessation was assessed 2 years after
      high school. SETTING: Forty Washington State school districts participated in the
      Hutchinson Smoking Prevention Project. PARTICIPANTS AND MEASUREMENTS:
      Participants were the 1553 families in which parents were ever regular smokers
      who had a young adult child smoking at least weekly at 12th grade who also
      reported their smoking status 2 years later. Questionnaire data were gathered on
      parents and their young adult children (49% female and 91% Caucasian) in a cohort
      with a 94% retention rate. FINDINGS: Parents who quit early had children with 1.8
      (OR = 1.80; 95% CI = 1.22, 2.64) times higher odds of quitting smoking for at
      least 1 month in young adulthood compared to those whose parents did not quit
      early. In contrast, there was no association (OR = 0.84; 95% CI = 0.47, 1.51)
      between parents quitting late and their young adult children's smoking cessation.
      CONCLUSIONS: Parental early smoking cessation is associated with increased odds
      of their young adult children's smoking cessation. Parents who smoke should be
      encouraged to quit when their children are young.

PMID- 15733252
TI  - Context-dependency of cue-elicited urge to smoke.
AB  - AIMS: Earlier studies have suggested that the cue-induced urge to smoke depends
      on the expectation of the availability of smoking. The present study investigated
      whether a 'room context' change could undo the learned discrimination between two
      stimuli, respectively, predicting smoking availability or smoking unavailability.
      DESIGN: A 2 (smoking cue) x 2 (availability context cue) x 6 (trial) x 2 (room
      context change) within-subjects design was used. Participants were repeatedly
      presented with a context cue predicting smoking availability (blue serving tray)
      and a context cue predicting unavailability (yellow serving tray) in one room and
      tested for an effect of context change in a different room. SETTING: Two distinct
      rooms located in different department buildings of Maastricht University.
      PARTICIPANTS: Seventeen daily smokers who had smoked at least five cigarettes a
      day for at least 2 years. MEASUREMENTS: Self-reported urge to smoke using a
      visual analogue scale (VAS). FINDINGS AND CONCLUSIONS: Results replicated the
      finding that a context cue that predicted smoking elicited greater urges to smoke
      than a context cue that predicted no smoking, irrespective of the presence of
      smoking cues. In addition, this study showed that this differential effect on the
      urge to smoke was generalized to a context other than the context in which
      learning took place. These findings are discussed in relation to the significance
      of a context change regarding the predictive value of smoking availability.

PMID- 15733253
TI  - Calling emergency medical services during drug overdose: an examination of
      individual, social and setting correlates.
AB  - AIMS: The purpose of this study was to examine individual, social and setting
      correlates of calling the emergency number, 911, during an overdose. DESIGN:
      Cross-sectional survey. METHODS: A sample of 397 current or former drug users in
      Baltimore, MD, USA who reported having ever witnessed an overdose. FINDINGS:
      Participants reported calling an ambulance in 23% of the overdose cases. Results
      from multivariate logistic regression indicate that having ever overdosed and
      having four or more bystanders present independently decreased the likelihood of
      calling 911. Having ever witnessed a fatal overdose and having any female
      bystanders present increased the likelihood of calling 911. There was a
      significant interaction between fear of arrest and prior exposure to the police.
      Setting of the overdose (public versus private) was not associated with calling
      911 after controlling for other factors. CONCLUSIONS: These findings suggest that
      in addition to personal characteristics of witnesses, social factors influence
      calling 911. Intervention at the social level may be a viable means to increase
      bystander helping behaviors.

PMID- 15733254
TI  - Influence of psychiatric comorbidity in alcohol-dependent subjects in a
      representative population survey on treatment utilization and natural recovery.
AB  - BACKGROUND: It is well known that only a minority of alcohol-dependent subjects
      seek help and that the majority of alcohol-dependent individuals recover without
      utilization of formal help. Psychiatric comorbidity is highly prevalent among
      alcohol-dependent individuals. However, no data are available on the impact of
      psychiatric comorbidity on natural recovery. AIMS: To analyse the impact of non
      psychotic psychiatric comorbid Axis I disorders on remission rate and utilization
      of formal help in alcohol-dependent individuals drawn from a representative
      general population sample in northern Germany (response rate: 70.2%, n = 4075).
      Psychiatric diagnoses and utilization of help were assessed in a personal
      interview using standardized instruments. One hundred and fifty-three life-time
      alcohol-dependent individuals were assessed, among whom 98 fulfilled the criteria
      for sustained long-term remission according to the Diagnostic and Statistical
      Manual version II (DSM-IV) criteria. Any coincidence of DSM-IV non-psychotic Axis
      I disorders with alcohol dependence was counted as comorbidity. Comorbidity rate
      in the whole sample was 36.1%. RESULTS: The rate of individuals who remitted from
      alcohol dependence without formal help was 36.9% in the non-comorbid and 42.6% in
      the comorbid group. Utilization of formal help was unrelated to comorbidity.
      Dually diagnosed subjects without a history of help-seeking showed minor
      differences concerning reasons for not seeking help. Seeking help was not related
      to schooling, severity of dependence and gender. CONCLUSION: Data reveal that
      remission without formal help is equally prevalent among non-comorbid as among
      comorbid alcohol-dependent individuals. Axis I comorbidity is not related
      directly to utilization of alcohol-related help. Negative prognoses for untreated
      comorbid alcohol-dependent individuals are not justified from an epidemiological
      point of view.

PMID- 15733260
TI  - Genetics of individual differences in bitter taste perception: lessons from the
      PTC gene.
AB  - The ability or inability to taste the compound phenylthiocarbamide (PTC) is a
      classic inherited trait in humans and has been the subject of genetic and
      anthropological studies for over 70 years. This trait has also been shown to
      correlate with a number of dietary preferences and thus may have important
      implications for human health. The recent identification of the gene that
      underlies this phenotype has produced several surprising findings. This gene is a
      member of the T2R family of bitter taste receptor genes. It exists in seven
      different allelic forms, although only two of these, designated the major taster
      and major non-taster forms, exist at high frequency outside sub-Saharan Africa.
      The non-taster allele resides on a small chromosomal region identical by descent,
      indicating that non-tasters are descended from an ancient founder individual, and
      consistent with an origin of the non-taster allele preceding the emergence of
      modern humans out of Africa. The two major forms differ from each other at three
      amino acid positions, and both alleles have been maintained at high frequency by
      balancing natural selection, suggesting that the non-taster allele serves some
      function. We hypothesize that this function is to serve as a receptor for
      another, as yet unidentified toxic bitter substance. At least some of the
      remaining five haplotypes appear to confer intermediate sensitivity to PTC,
      suggesting future detailed studies of the relationships between receptor
      structure and taste function.

PMID- 15733261
TI  - Glyc-O-genetics of Walker-Warburg syndrome.
AB  - Walker-Warburg syndrome (WWS) is the most severe of a group of multiple
      congenital anomaly disorders known as the cobblestone lissencephalies. These are
      characterized by congenital muscular dystrophy in conjunction with severe brain
      malformation and ocular abnormalities. In the last 3 years, important progress
      has been made towards the elucidation of the genetic causes of these disorders.
      Mutations in three genes, POMT1, fukutin and FKRP, have been described for WWS,
      which together account for approximately 20% of patients with Walker-Warburg. It
      has become evident that some of the underlying genes may cause a broad spectrum
      of phenotypes, ranging from limb girdle muscular dystrophy type 2I to WWS. In
      some cases, a genotype-phenotype correlation can be recognized. In line with the
      known or proposed functions of the resolved genes, all patients with cobblestone
      lissencephaly show defects in the O-linked glycosylation of the glycoprotein
      alpha-dystroglycan. Perhaps, the missing genes underlying the remainder of the
      unexplained WWS patients have also to be sought in the pathways involved in O
      linked protein glycosylation.

PMID- 15733262
TI  - The ZIC gene family in development and disease.
AB  - The human ZIC gene family is comprised of five members encoding zinc-finger
      transcription factors, which are the vertebrate homologs of the Drosophila odd
      paired gene. Mutations in ZIC genes in humans have recently been implicated in a
      wide variety of congenital malformations, including Dandy-Walker malformation,
      holoprosencephaly, neural tube defects, and heterotaxy. Mutant analysis of these
      genes in mice has underscored the conserved developmental roles of these genes.
      Further, this analysis has begun to elucidate the molecular and developmental
      mechanisms underlying these important birth defects.

PMID- 15733266
TI  - A randomized trial comparing alternative approaches to prenatal diagnosis
      counseling in advanced maternal age patients.
AB  - Prenatal diagnosis (PND) is offered routinely as part of pregnancy care to a
      large number of women at increased risk of fetal anomalies. Despite an
      extraordinary growth in the use of PND and significant resource allocation, few
      studies have examined outcomes of PND counseling, and virtually no research has
      evaluated the relative efficacy of various approaches to genetic counseling. This
      study was a randomized trial that compared which counseling methods - individual,
      group, and use of a decision aid - are effective in PND counseling for women of
      advanced maternal age (>/=35 years) and their partners. Three hundred and fifty
      two women and 225 partners completed pre- and post-intervention questionnaires
      assessing changes in knowledge, decisional conflict, state anxiety, satisfaction,
      use of PND, and pregnancy outcomes. All participants showed a significant
      increase in knowledge and a decrease in decisional conflict post intervention.
      Those in the group intervention showed a significantly greater increase in
      knowledge than those in the individual counseling intervention. While high levels
      of satisfaction were reported by all, those in individual counseling were
      significantly more satisfied than those receiving group counseling or the
      decision aid. This study has shown unique benefits with each type of intervention
      such that women and their partners preferred individual genetic counseling, while
      they learned best in group-counseling sessions, and experienced the least
      decisional conflict regarding genetic testing with a decision aid.

PMID- 15733267
TI  - LARALink: a web application for cytogenetic linkage analysis.
AB  - Genomic and expression data have increased dramatically over the last several
      years. This is primarily due to the completion of the human genome project as
      well as an upsurge in the use of various high-throughput technologies. Recent
      attempts to correlate genomic and expression data have stimulated the scientific
      community to determine how this data can be used within a clinical setting (P
      Khatri et al., Genomics 2002: 79: 266; LJ van't Veer et al., Nature 2002: 415:
      530). LARALink (Loci Analysis for Rearrangements Link) is a database-driven web
      application that utilizes several public datasets to analyze clinical cytogenetic
      data to identify candidate genes. LARALink allows UniGene clusters or single
      nucleotide polymorphisms (SNPs) to be queried for multiple patients by cytoband,
      chromosome marker, or base pair. The results can be further refined with the use
      of an anatomical site, developmental stage, pathology, or cell-type expression
      filter. Once a set of UniGene clusters (expressed genes) has been identified
      either for a single patient or for a shared region among multiple patients, the
      expression-distribution profile, expressed sequence tags (ESTs), or online
      mendelian inheritance in man (OMIM) entries are displayed. The utility of this
      tool is shown by its application to both research and clinical medicine. LARALink
      is a public resource available at:
      http://www.laralink.bioinformatics.wayne.edu:8080/unigene.

PMID- 15733268
TI  - Identification of germline BRCA1 and BRCA2 genetic alterations in Greek breast
      cancer moderate-risk and low-risk individuals--correlation with
      clinicopathological data.
AB  - The current study was designed to evaluate the prevalence of BRCA1 and BRCA2
      germline mutations in Greek moderate- and low-risk individuals with respect to
      clinicopathological phenotype and clinical outcome of breast cancer. Ninety-four
      consecutive individuals were prospectively recruited from two University Breast
      Cancer Clinics (Hippokrateion Hospitan and Laikon Hospital) between 1989 and 1999
      and were categorized as moderate-risk and low-risk individuals for carrying
      BRCA1/2 germline mutations. To identify the underlying mutations, protein
      truncation test and single-strand conformation polymorphism methods were used,
      followed by direct sequencing. Three novel BRCA1 missense mutations, one novel
      BRCA1 intronic deletion, three novel (previously reported) BRCA2 truncating
      mutations, and one novel BRCA2 missense mutation were identified in the moderate
      risk group of individuals studied. The BRCA1/2 missense mutations as well as the
      single intronic variant identified were designated as unclassified genetic
      variants. Two BRCA1 unclassified genetic variants (missense mutations) were
      detected in two of the three (66.7%) male breast cancer patients analyzed, while
      the third one was identified in a sporadic (low-risk) breast cancer patient.
      Clinicopathological characteristics of breast carcinomas originating from BRCA1/2
      heterozygotes were consistent with those already reported and not different from
      those observed in BRCA1/2 mutation (-) breast cancer patients. Furthermore,
      BRCA1/2 mutation carriers presented an excellent 4.5-year overall survival
      (100%). Our results reveal the unique characteristics of BRCA1/2 mutation status,
      genotype-phenotype correlations, and prognosis, in moderate- and low-risk
      individuals of Greek ancestry. Breast cancer due to mutations in BRCA1 and BRCA2
      genes appears to be a heterogeneous syndrome in the Greek population.

PMID- 15733269
TI  - Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients
      with tenascin-X mutations.
AB  - Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue
      disorders with characteristic skin and joint involvement. The concept that EDS is
      a disease of fibrillar collagen was challenged by the identification of a
      clinically distinct, recessive type of EDS caused by deficiency of the
      extracellular matrix protein tenascin-X (TNX). Interestingly, haploinsufficiency
      of TNX is associated with the dominantly inherited hypermobility type of EDS. In
      this study, we examined whether missense mutations in the TNX gene can account
      for some of the cases of hypermobility type EDS. Furthermore, we studied whether
      missense mutations or heterozygosity for truncating mutations in the TNX gene
      lead to alterations in the dermal connective tissue. Sequence analysis revealed
      three missense mutations in TNX in hypermobility type EDS patients, which were
      not present in 192 control alleles. Morphometric analysis of skin biopsies of
      these patients showed altered elastic fibers in one of them, suggesting that this
      missense mutation is disease causing. Light microscopic and ultrastructural
      changes of the elastic fibers were observed in TNX-haploinsufficient
      hypermobility type EDS patients, which were not found in hypermobility type EDS
      patients in whom TNX mutations were excluded. Our results indicate that the
      observed alterations in elastic fibers are specific for hypermobility type EDS
      patients with mutations of TNX.

PMID- 15733270
TI  - Myocilin gene implicated in primary congenital glaucoma.
AB  - Primary congenital glaucoma (PCG) has been associated with CYP1B1 gene (2p21),
      with a predominantly autosomal recessive mode of inheritance. Our earlier studies
      attributed CYP1B1 mutations to only 40% of Indian PCG cases. In this study, we
      included 72 such PCG cases where CYP1B1 mutations were detected in only 12
      patients in heterozygous condition, implying involvement of other gene(s). On
      screening these patients for mutations in myocilin (MYOC), another glaucoma
      associated gene, using denaturing high-performance liquid chromatography followed
      by sequencing, we identified a patient who was double heterozygous at CYP1B1
      (c.1103G>A; Arg368His) and MYOC (c.144G>T; Gln48His) loci, suggesting a digenic
      mode of inheritance of PCG. In addition, we identified the same MYOC mutation,
      implicated for primary open angle glaucoma, in three additional PCG patients who
      did not harbor any mutation in CYP1B1. These observations suggest a possible role
      of MYOC in PCG, which might be mediated via digenic interaction with CYP1B1
      and/or an yet unidentified locus associated with the disease.

PMID- 15733271
TI  - A variant Cri du Chat phenotype and autism spectrum disorder in a subject with de
      novo cryptic microdeletions involving 5p15.2 and 3p24.3-25 detected using whole
      genomic array CGH.
AB  - Cri du Chat syndrome (CdCs) is a well-defined clinical entity, with an incidence
      of 1/15,000 to 1/50,000. The critical region for CdCs has been mapped to 5p15,
      with the hallmark cat-like cry sublocalized to 5p15.3 and the remaining clinical
      features to 5p15.2. We report findings in a subject with a de novo
      t(5;7)(p15.2;p12.2) and an inv(3)(p24q24), who was found to have a cryptic
      microdeletion in the critical region for CdCs detected using a 1-Mb genomic
      microarray. In addition to 5p deletion, the proband had a de novo single clone
      loss at the 3p breakpoint of inv(3)(p24q24) and a familial single clone deletion
      at 18q12. Deletions were confirmed using microsatellite analysis and fluorescence
      in situ hybridization. The 5p deletion encompasses approximately 3 Mb, mapping to
      the border between bands 5p15.2 and 5p15.31. The single clone deletion on
      chromosome 3 maps to 3p24.3-3p25, for which there is no known phenotype. The
      clinical features of our proband differ from the characteristic CdC phenotype,
      which may reflect the combined effect of the two de novo microdeletions and/or
      may further refine the critical region for CdCs. Typical features of CdCs that
      are present in the proband include moderate intellectual disability, speech, and
      motor delay as well as dysmorphic features (e.g. broad and high nasal root,
      hypertelorism, and coarse facies). Expected CdCs features that are not present
      are growth delay, microcephaly, round facies, micrognathia, epicanthal folds, and
      the signature high-pitched cry. Behavioral traits in this subject included autism
      spectrum disorder, attention-deficit hyperactivity disorder, and unmanageable
      behavior including aggression, tantrums, irritability, and self-destructive
      behavior. Several of these behaviors have been previously reported in patients
      with 5p deletion syndrome. Although most agree on the cat-cry critical region
      (5p15.3), there is discrepancy in the precise location and size of the region
      associated with the more severe manifestations of CdCs. The clinical description
      of this proband and the characterization of his 5p deletion may help to further
      refine the phenotype-genotype associations in CdCs and autism spectrum disorder.

PMID- 15733272
TI  - The I1307K APC mutation in a high-risk clinic setting: a follow-up study.
AB  - While the I1307K APC mutation clearly confers an increased lifetime risk for
      colorectal cancer, there is a paucity of data on the natural history of colonic
      neoplasia in symptomatic and asymptomatic mutation carriers. In this study, 51
      Jewish I1307K APC mutation carriers were identified in a high-risk familial
      cancer clinic over a 4-year period, of whom 29 (56.8%) (four males and 25
      females) were successfully telephone interviewed for 0.5-5 years (mean 2.4 +/-
      1.4) after initial genetic testing. Of these 29 cases, one individual was
      diagnosed with colon cancer at the age of 45 years, five had adenomatous polyps
      (mean number of polyps = 1.8), 11 had breast cancer (mean age at diagnosis 49.5
      +/- 10.5 years), and 12 were asymptomatic, at the time of the testing. During the
      follow-up period, new colonic polyps were diagnosed in three mutation carriers,
      two with previously diagnosed colon cancer and polyps and only one of the
      asymptomatic mutation carriers, and two additional previously affected patients
      had new cancer diagnoses: gastric cancer and melanoma. From this descriptive
      study, it seems that the short-term risk for colonic polyps in I1307K APC
      mutation is low, primarily affecting patients with previously diagnosed colon
      tumors.

PMID- 15733273
TI  - Novel mutations in the calpain 3 gene in Germany.

PMID- 15733274
TI  - Association of COL1A2, COL2A1 and COL9A1 and primary osteoarthritis in a founder
      population.

PMID- 15733275
TI  - A search for the gene(s) predisposing to idiopathic clubfoot.

PMID- 15733276
TI  - Genetic variants of frizzled-4 gene in familial exudative vitreoretinopathy and
      advanced retinopathy of prematurity.

PMID- 15733277
TI  - Xp22.3 microdeletion including VCX-A and VCX-B1 genes in an X-linked ichthyosis
      family: no difference in deletion size for patients with and without mental
      retardation.

PMID- 15733278
TI  - Mental Health Nursing: challenging stigma and discrimination towards people
      experiencing a mental illness.

PMID- 15733279
TI  - Providing emergency mental health care to asylum seekers at a time when claims
      for permanent protection have been rejected.
AB  - In total, 90% of 'boat people' who make it to Australia's migration zone are
      assessed as legitimate refugees and given Temporary Protection Visas (TPV)
      allowing them to stay in Australia for 3 years in the first instance. With an
      increasing number of individuals and families on TPV having their claims for a
      Permanent Protection Visa (PPV) rejected, this paper argues using the National
      Mental Health Plan 2003-2008 as a guide, for interventions that are culturally
      and linguistically appropriate, thus, aiming to minimize risk from exposure to
      extreme mental stressors in the event of an application for a PPV being rejected.
      Continuity and integration of mental health care involving key stakeholders is
      best achieved by bridging discrete elements through preparing for visa appeals
      and reviews, news from home and ongoing psychosocial stressors--in the context of
      different episodes, interventions by different providers, and changes in mental
      distress. To help strengthen continuity and integration of mental health supports
      for TPV holders, well resourced care must be experienced as connected and
      coherent.

PMID- 15733280
TI  - Adversity as opportunity: living with schizophrenia and developing a resilient
      self.
AB  - Approximately 1% of the population is diagnosed with schizophrenia, and despite
      longstanding critiques of the (bio)medical model, understanding of the disorder
      still arises primarily through (bio)medical explanations. In turn, causation,
      symptoms and treatments are increasingly sophisticated and well known while
      understanding of other aspects of the disorder, especially the intersubjective
      experience of people living with schizophrenia, remains fragmented. For this
      reason, the present study sought to understand how people experience
      schizophrenia. To do this, the stories of 19 people diagnosed with the disorder
      were hermeneutically interpreted. These stories appeared in The Schizophrenia
      Bulletin--a journal which publishes 'first person accounts', sometimes
      anonymously, of people's experience of mental illness. Within the study context,
      the findings indicate that facing the adversity of schizophrenia means living:
      (i) wisely--understanding the nature of self-with-schizophrenia and of life-with
      schizophrenia; (ii) mindfully--keeping understandings in conscious thought; and
      (iii) purposefully--acting deliberately. Doing this results in a stable and
      meaningful life and in a different, more resilient self.

PMID- 15733281
TI  - An investigation of aged care mental health knowledge of Queensland aged care
      nurses.
AB  - Older people are at risk for developing psychiatric disorders and require highly
      skilled and knowledgeable nurse practitioners to provide early recognition and
      intervention of psychiatric problems. This study sought to identify the aged care
      mental health knowledge of registered nurses (RNs) employed in long-term aged
      care and test the validity and reliability of a North American tool for use in an
      Australian context. The Mary Starke Harper Ageing Knowledge Exam (MSHAKE) was
      sent to RNs (n = 350) in 70 long-term care facilities (LTCF) in Queensland,
      Australia, and 107 surveys were returned (30.5% response). Participants were
      found to be unprepared for the reality of caring for the mental health needs of
      an older population and to have knowledge deficits related to suicide, prevalence
      of mental illness, mental health and ethnicity, and a number of issues regarding
      dementia.

PMID- 15733282
TI  - Interpersonal psychotherapy: an effective psychotherapeutic intervention for
      mental health nursing practice.
AB  - Interpersonal psychotherapy (IPT) is well-recognized for the treatment of
      depression with many efficacy trials supporting its use, however, there is little
      discussion of its use in mental health nursing practice. This paper explores how
      IPT can be a useful intervention for mental health nursing practice and
      demonstrates the process of IPT with reference to a case study. The case study
      illustrates how IPT facilitates a shift for one woman from a passive subject
      position to a more self-assertive one. This shift was facilitated by identifying
      how she was constructing herself in relation to others by utilizing tactics of
      passivity and avoidance of conflict. The development of more satisfying subject
      positions facilitated an improvement in mood and recovery from depression.

PMID- 15733283
TI  - Towards a healthier lifestyle for staff of a psychiatric hospital: description of
      a pilot programme.
AB  - Various lifestyle factors contribute to morbidity and mortality. Health promotion
      programs have the potential to increase awareness about, and possibly modify,
      some of these factors. In the workplace, these programs can be accessed by large
      groups of people. A healthy lifestyles programme was piloted for non-clinical
      staff in Central Sydney Area Mental Health Service, Australia. The aim of the
      programme was to provide non-clinical staff working in a mental health setting
      with education and information on a range of health conditions and topics. A
      needs analysis survey, along with formal and informal liaison and discussion,
      informed the programme's development and implementation. A total of 28 sessions
      were held; attendance ranged from 1 to 51 with a mean of 13.57 and a median of
      12.5. Feedback regarding the programme has generally been positive. This pilot
      demonstrates that nurses, with their colleagues from other disciplines, are well
      positioned to deliver health promotion and education initiatives that may
      contribute to increasing awareness, and possibly modification, of lifestyle
      factors.

PMID- 15733284
TI  - Seclusion of children and adolescents: psychopathological and family factors.
AB  - This paper describes the use of seclusion in a child and adolescent inpatient
      unit, including precipitating events, management strategies, details of seclusion
      episodes and individual and family risk factors. Inpatient ward documentation of
      seclusion episodes, demographic data and measures of individual psychopathology
      and impairment, parent mental health, life events and family functioning were
      used to compare secluded, non-secluded and outpatient groups. Secluded
      individuals had elevated psychopathology compared with non-secluded inpatients
      and outpatients. Their families reported poorer parental mental health and family
      functioning and more recent stressful life events. The results indicate that
      seclusion is most common among high-risk inpatients.

PMID- 15733285
TI  - Nurses under threat: a comparison of content of 28 aggression management
      programs.
AB  - Staff who work in the health service are now recognized as a high-risk group for
      assault in the workplace. Recently, professional and industrial organizations
      have begun to suggest appropriate curricula for training staff in aggression
      management. However, there is currently a plethora of aggression management
      training programs (AMP) available, varying both in content and in duration. In
      this paper, 28 programs were evaluated against 13 major content areas derived
      from the recommendations made from key professional and industrial organizations,
      and what may be today considered appropriate/ideal content areas for AMP.
      Information on programs available in English was sought via standard databases,
      the Internet, program providers, and through networking with colleagues and
      professional organizations. The majority of the programs reviewed covered
      personal safety issues for staff and patients, together with legal issues. The
      use of restraint, pharmacological management of aggression and seclusion were
      features of programs specifically addressing the needs of health care staff in
      mental health settings. Most programs appeared not to address the psychological
      and organizational costs associated with aggression in the workplace. This is
      surprising since the literature suggests that the effects of violence are wide
      and varied, including increased absenteeism and sick leave, property damage,
      decreased productivity, security costs, litigation, workers' compensation,
      reduced job satisfaction together with recruitment and retention issues. Also,
      few programs were based on a systematic evaluation of their outcomes. Suggestions
      for program development and their teaching are discussed.

PMID- 15733286
TI  - Attempting to accomplish connectedness within the preceptorship experience: the
      perceptions of mental health nurses.
AB  - The provision of sound support models for clinical practicum is recognized as
      integral to the development of nursing students and their transition to
      registered nurses. In mental health settings, there is the additional issue of
      positively influencing recruitment rates. Preceptorship has been widely adopted
      nationally and internationally, however, there is a paucity of research,
      particularly in mental health settings, to assess its effectiveness. The current
      study utilized a grounded theory approach to explore the experience of
      preceptorship for mental health nurses. The findings suggest that mental health
      nurses seek to accomplish connectedness in the preceptorship relationship. A
      number of factors inhibit the degree of success in achieving this connectedness,
      including fear of mental health settings, misconceptions about mental illness and
      organizational constraints.

PMID- 15733287
TI  - Email etiquette: guidelines for mental health nurses.
AB  - This note is about the use of email and its role in mental health settings. We
      anticipate that it may be of assistance to mental health nurses unfamiliar with
      the benefits and pitfalls of email and wanting to learn more about how to use it
      professionally and effectively. In mental health nursing, we pride ourselves on
      our interpersonal skills and being able to communicate. However, transferring
      these skills to an electronic medium is not always easy. Because many of us are
      self-taught, there is potential for email to be a hindrance rather than a help in
      the quest for good collegial relationships. In this note, we discuss some of the
      common situations that can arise when email use goes awry and provide some
      helpful tips for getting the most out of email. It is hoped that the information
      and checklist provided in this paper will strike a chord with many, encouraging
      discussion and promoting appropriate use of this form of communication.

PMID- 15733291
TI  - Gordon L. Ruskell: optometrist, teacher and anatomist.

PMID- 15733292
TI  - Re-evaluation and quantification of the different sources of nerve fibres
      supplying the rat eye.
AB  - The denervation and/or the removal of peripheral nerve ganglia are useful
      surgical techniques for studying the source and distribution of peripheral nerves
      in all organs, including the eye. The amount and distribution of the remaining
      nerve fibres supplying the eye (after sectioning of various types of nervous
      fibres and/or removal of nerve ganglia) were evaluated in the rat. Male Sprague
      Dawley rats were anaesthetized and one or more of the following nervous tissues
      were removed: superior cervical ganglion, main ciliary ganglion, pterygopalatine
      ganglion, trigeminal ganglion and the ophthalmic-maxillary nerve. In some
      animals, chemical sympathectomy was performed by administration of 6-OH dopamine.
      The eyes were cut in serial sections, but only three regions (cornea, iris and
      choroid) were harvested and submitted for various nerve fibre staining
      techniques. The results were quantified and statistically analysed. Superior
      cervical ganglionectomy and/or chemical sympathectomy induced the destruction of
      almost all the catecholaminergic nerve fibres in the three examined regions of
      the rat eye. Removal of the ciliary ganglion (partial parasympathectomy) caused
      the destruction of about 60% of the cholinergic nerve fibres of the same regions
      of the rat eye, while subtotal parasympathectomy destroyed about 80% of the
      cholinergic nerve fibres. Surgical transsection of the ophthalmo-maxillary nerve
      or the removal of the trigeminal ganglion led to a degeneration of almost all
      sensitive nerve fibres of the three examined regions of the rat eye. The
      denervation experiments confirmed the presence of the different types of nerve
      fibres (sympathetic, parasympathetic and sensitive) in the three studied
      structures of the rat eye.

PMID- 15733293
TI  - The origin of extrinsic nitrergic axons supplying the human eye.
AB  - Nitrergic nerve fibres of intrinsic and extrinsic origin constitute an important
      component of the autonomic innervation in the human eye. The intrinsic source of
      nitrergic nerves are the ganglion cells in choroid and ciliary muscle. In order
      to obtain more information on the origin of extrinsic nitrergic nerves in the
      human eye, we obtained superior cervical, ciliary, pterygopalatine and trigeminal
      ganglia from six human donors, and stained them for neuronal nitric oxide
      synthase (nNOS) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH
      D). In the superior cervical ganglia, nNOS/NADPH-D-positive varicose axons were
      observed whereas perikarya were consistently negative. Fewer than 1% of perikarya
      in the ciliary ganglia were labelled for nNOS/NADPH-D. The diameter of nNOS/NADPH
      D-positive ciliary perikarya was between 8 and 10 microm, which was markedly
      smaller than the diameter of the vast majority of negative perikarya in the
      ciliary ganglion. More than 70% of perikarya in the pterygopalatine ganglia were
      intensely labelled for both nNOS and NADPH-D. In trigeminal ganglia, 18% of
      perikarya were nNOS/NADPH-D-positive. The average diameter of trigeminal
      nNOS/NADPH-D perikarya was between 25 and 45 microm. Pterygopalatine and
      trigeminal ganglia are the most likely sources for extrinsic nerve fibres to the
      human eye.

PMID- 15733294
TI  - Innervation of the porcine ciliary muscle and outflow region.
AB  - The porcine eye serves as a model to study various functions of the aqueous
      outflow system. To compare these data with the primate eye, a detailed
      investigation of the distribution of contractile properties and of the
      innervation of the outflow region was conducted in the porcine eye. In all
      quadrants of the anterior eye segment, elastic fibres connected the ciliary
      muscle (CM) with the well-developed scleral spur (ScS) and also partly with the
      corneoscleral trabecular meshwork (TM) and the loops of the collecting outflow
      channels. Immunohistochemistry with antibodies against smooth muscle alpha-actin
      revealed intense staining of the CM and some myofibroblasts in the ScS and outer
      TM. In addition to a few cholinergic and aminergic nerve fibres in the outflow
      region, numerous substance P- and calcitonin-gene related peptide-positive nerve
      fibres and nerve endings were found near the outflow loops of the porcine TM.
      Although the porcine CM serves rather as a tensor choroideae muscle than as a
      muscle for accommodation, the innervation and morphology of the collecting
      outflow channel loops and of the expanded TM between the ScS and the cornea
      showed close similarities to the primate eye.

PMID- 15733295
TI  - Substance P and opioid peptidergic innervation of the anterior eye segment of the
      rat: an immunohistochemical study.
AB  - Recently discovered endogenous opioid peptides such as nociceptin are known to
      modulate neurotransmitter release of primary afferent neurons (especially
      substance P, SP) and they have also been demonstrated in peripheral nerve fibres.
      The aim of this study was to investigate the opioid peptidergic innervation of
      the anterior eye segment and to compare it with the innervation pattern of SP in
      order to shed light on the functional relationship between these peptides.
      Anterior eye segments of 20 rat eyes were cut in a tangential plane and the
      sections stained with antibodies against SP, nociceptin, nocistatin, endomorphin
      1 and 2, leu-enkephalin and met-enkephalin. Sections of the spinal cord or brain
      were used as positive controls. Numerous SP-immunoreactive nerve fibres were
      found in the conjunctiva, cornea, episclera, trabecular meshwork, iris and
      ciliary body. A weak staining for met-enkephalin and leu-enkephalin could only be
      found in the iris and anteriormost ciliary body. Nerve fibres immunoreactive for
      nociceptin, nocistatin, and endomorphin 1 or 2 could not be detected in any part
      of the anterior eye segment. It is tempting to speculate that the opioid
      peptidergic innervation of the anterior ciliary body may play a role in the
      modulation of intraocular inflammation.

PMID- 15733296
TI  - The human choriocapillaris: evidence for an intrinsic regulation of the
      endothelium?
AB  - The aim of the present study was to describe the ultrastructure of particular
      cells observed in the microvascular bed of the healthy human choroid, in close
      relation to the wall of the microvessels and resembling the periadventitial cells
      of other vascular areas of the human body. Serial sections of 12 fresh human eyes
      were studied by transmission electron microscopy. In all the eyes, the sections
      were obtained by cutting from the same zones (inner and outer choroid at the
      posterior pole of the eye). Standard techniques were used for transmission
      electron microscopy. Round cell bodies were found in the inner choroid at the
      posterior pole of the eye, mainly located in the intercapillary connective
      tissue. The cells were composed of an electron-transparent cytoplasm containing a
      few small mitochondria, and a dilated smooth surface of endoplasmic reticulum, at
      some points continuous with the nuclear membrane. These cells showed processes
      forming contact with the capillary wall. Some of these processes extended to the
      elastic layer of Bruch's membrane, but none had contact with the retinal pigment
      epithelium. A thin basement membrane surrounded both the cell bodies and
      processes. We believe that these cells are special cells resembling some type of
      periendothelial cells also localized in other microvascular districts of the
      human body. The close topographic correlation with the endothelial cells seems to
      indicate that these special cells play a role in the intrinsic control of proper
      endothelial functions.

PMID- 15733297
TI  - Somatostatin immunoreactivity in quail pterygopalatine ganglion.
AB  - In the ciliary ganglion of the chicken and quail, somatostatin (SOM) is an
      exclusive marker for parasympathetic postganglionic neurons innervating the
      choroid. A second parasympathetic pathway projecting to the choroid originates
      from the pterygopalatine ganglion. The aim of this study was to investigate SOM
      immunoreactivity in the pterygopalatine ganglion of the Japanese quail (Coturnix
      coturnix japonica) and on neurons within the choroid, the intrinsic choroidal
      neurons (ICN). We did so using immunohistochemistry and subsequent light,
      electron and confocal laser scanning microscopy. Pterygopalatine neurons were
      characterized by nNOS-immunohistochemistry or NADPH-diaphorase cytochemistry. SOM
      immunoreactivity was absent in the perikarya, but neurons were densely surrounded
      by SOM-positive nerve fibres. Electron microscopy revealed that these fibres
      formed contacts with and without membrane specializations on pterygopalatine
      neurons. In the choroid, neuronal nitric-oxide synthase (nNOS)-immunoreactive ICN
      were likewise closely apposed by SOM-immunoreactive nerve fibres, as revealed by
      confocal microscopy. There was no detectable co-localization of the markers. In
      the absence of tracing studies, it is open to speculation whether SOM
      immunoreactivity originates from preganglionic fibres of the superior salivatory
      nucleus, postganglionic fibres of the ciliary ganglion or fibres of the brainstem
      via as yet unknown pathways. SOM may regulate the production of NO in
      pterygopalatine neurons and ICN, respectively, and is therefore involved in
      neuronal circuits regulating ocular homeostasis.

PMID- 15733298
TI  - Connections between the lacrimal gland and sensory trigeminal neurons: a WGA/HRP
      study in the cynomolgous monkey.
AB  - The sensory innervation of the lacrimal gland (LG) in the cynomolgous monkey was
      studied using the retrograde wheat germ agglutinin/horsereadish peroxidase
      (WGA/HRP) tracer technique. A small solidified piece of WGA/HRP was implanted in
      the LG. Labelled sensory first-order neurons were found in the ipsilateral
      trigeminal ganglion (TG) and in the ipsilateral mesencephalic trigeminal nucleus
      (MTN). The distribution of labelled TG neurons was restricted to ophthalmic and
      maxillary ganglionic parts. Sensory innervation of LG by primary afferents is not
      only restricted to TG; an MTN involvement has also been found. This may imply
      that there is a central sensory role in the production and release of tears.

PMID- 15733299
TI  - Tear-film lipid layer morphology and corneal sensation in the development of
      blinking in neonates and infants.
AB  - The aim of the study was to evaluate the role of lipid layer thickness and
      corneal sensation in the development of blinking in neonates. The study group
      comprised sixty-four neonates and infants (mean age 27.5 +/- 15 (sd) weeks, range
      3.4-52) whose mothers were attending a general practice healthy baby clinic.
      Spontaneous eye-blink activity was determined from digital videographic
      recordings; tear film lipid layer morphology wasexamined using interference
      patterns produced by the Keeler Tearscopetrade mark Plus over a five-point
      grading scale (higher grades are associated with thick and stable lipid films);
      corneal sensation threshold was assessed with the Non-Contact Corneal
      Aesthesiometer (NCCA), using the eye-blink response as an objective indication
      that the cooling stimulus had been felt; palpebral aperture dimensions were
      measured using calibrated digital still images of the eye in the primary
      position. The overall mean spontaneous blink-rate was found to be 3.6 (+/- 0.3)
      blinks min(-1), and the mean interblink time was 21.6 (+/- 2.8) s. The lowest
      blink-rates were observed in the 0-17-week age group (average 2 blinks min(-1)).
      The blink-rate showed a highly significant correlation with age (r = 0.46, P <
      0.01). The overall mean lipid layer grading was 3.6 (+/- 0.2 SE) arbitrary units.
      Higher grades were found in the newborn and the mean grading score reduced with
      age (P < 0.01). The mean sensation threshold to blink (TTB) was 0.69 (0.04 SE)
      mbar, which did not differ from a control group of older subjects (P > 0.05).
      There was a rapid increase in palpebral aperture length and width from birth to 1
      year old, with surface area increasing by 50% over the same period. We concluded
      that the low rate of spontaneous eye blink activity in neonates is associated
      with a thick stable lipid layer that may be a function of a small palpebral
      aperture. Furthermore, neonates appear to have the capacity to detect ocular
      surface cooling, which is a major trigger for spontaneous blinking.

PMID- 15733300
TI  - The role of eye-associated lymphoid tissue in corneal immune protection.
AB  - Because the cornea is optimized for refraction, it relies on supporting tissues
      for moistening and nutrition and in particular for immune protection. Its main
      support tissue is the conjunctiva, in addition to the lacrimal gland, the latter
      which provides soluble mediators via the tear film. The cornea and conjunctiva
      constitute a moist mucosal surface and there is increasing evidence that apart
      from innate defence mechanisms, also lymphoid cells contribute to the normal
      homeostasis of the corneal surface. A Medline-based literature search was
      performed in order to review the existing literature on the existence,
      composition and functions of mucosa-associated lymphoid tissue (MALT) at the
      ocular surface for corneal protection. The existence of lymphoid cells at the
      ocular surface and appendage has been known for many years, but for a long time
      they were believed erroneously to be inflammatory cells. More recent research has
      shown that in addition to the known presence of lymphoid cells in the lacrimal
      gland, they also form MALT in the conjunctiva as conjunctiva-associated lymphoid
      tissue (CALT) and in the lacrimal drainage system as lacrimal drainage-associated
      lymphoid tissue (LDALT). Together this constitutes an eye-associated lymphoid
      tissue (EALT), which is a new component of the mucosal immune system of the body.
      When the topographical distribution of CALT is projected onto the ocular surface,
      it overlies the cornea during eye closure and is hence in a suitable position to
      assist the corneal immune protection during blinking and overnight. It can detect
      corneal antigens and prime respective effector cells, or distribute protective
      factors as secretory IgA.

PMID- 15733301
TI  - Cellular inflammatory response induced by sensory denervation of the conjunctiva
      in monkeys.
AB  - The inflammatory response induced by sensory denervation of the cornea,
      neuroparalytic (neurotrophic) keratitis, has been widely reported in the
      literature. Clinical evidence has shown that the conjunctiva also responds to
      sensory denervation, but little is known of the cytology of the conjunctival
      tissue response to denervation. The purpose of this study therefore was to
      investigate the cytological aspects of tissue response induced in the conjunctiva
      of monkeys by sensory denervation. Intracranial ophthalmic neurotomy was carried
      out in three monkeys, maxillary neurotomy in four, combined ophthalmic and
      maxillary neurotomy in two, and infraorbital nerve transaction in one monkey.
      These various operations were performed for other experimental purposes, but the
      conjunctival tissues from the animals were suitable and available to study the
      cytology of the inflammatory response induced in the tissue following the sensory
      denervation. The cytological changes were studied using light microscopy.
      Complete or severe ophthalmic nerve transection induced significant inflammatory
      responses, which were largely confined to the tarsal region of the conjunctiva.
      The responses included a substantial increase in the infiltration of the
      epithelium by polymorphonuclear leucocytes and severe disruption of the
      epithelium. The number of macrophages in the conjunctiva also increased. The
      response induced by maxillary denervation, however, was not as pronounced as that
      induced by sensory denervation. The restriction of the conjunctival tissue
      response to the tarsal region was considered to be due to the friction between
      the tarsal conjunctiva (and the hard tarsal plate) and the cornea during
      blinking. This study shows that sensory denervation of the conjunctiva elicits an
      inflammatory response characterized by substantial infiltration of the epithelium
      by neutrophil and macrophage and disorganization of the conjunctival tissue.

PMID- 15733302
TI  - Double insertions of extraocular rectus muscles in humans and the pulley theory.
AB  - Recent studies have promoted the concept that rectus muscles pass through
      connective tissue pulleys located near the equator of the eye and act, in effect,
      as the muscle origins. Orbital muscle fibres (facing bone) terminate in pulleys,
      permitting adjustment of their position independent of the global fibres
      responsible for rotating the eye. The structure of pulleys (or muscle sleeves)
      and the passage taken by their muscle fibre insertions are unclear, and a
      detailed description is presented here together with a review of the active
      pulley hypothesis. Segments including the full width of single muscles were
      removed from the full orbital contents of dissection room cadavers and fresh
      perfusion-fixed rhesus and cynomolgus monkeys and prepared for light microscopy.
      Thin longitudinal sections were cut as facets from resin-embedded tissue blocks
      and montages assembled. Interrupted serial sections of selected regions of both
      species and ultrathin sections of monkey material were prepared for light and
      electron microscopy, respectively. Slender tendons leave the orbital surface of
      rectus muscles at intervals, aggregating and entering sleeves in humans and
      monkey; less frequently, tendons pass from the global surface to sleeves or
      insert directly in the posterior fascia bulbi. The orbital sides of sleeve rings
      are continuous with the fascial canopy of the globe and are 5-6 times as thick as
      the global sides; sleeve structure differs in the four recti. Medial rectus
      sleeves are the thickest, and contain smooth muscle, whereas little or none is
      present in the other rectus sleeves. Superior rectus sleeves are variable in
      structure and relatively insubstantial. A narrow interval separates muscles from
      the surrounding connective tissue equatorially in some preparations, consistent
      with a capacity to slide, but the tissues are contiguous in others, especially in
      monkey material. The structural organization of sleeves and their tendons,
      together with other presented factors, is inconsistent with a facility for the
      separate adjustment of sleeve position. The results favour the theory that sleeve
      tendons have just one role, to counter the viscoelastic resistance of global
      fascia - ocular and sleeve muscle fibres acting in unison. Whether the fragile
      sleeve structure can meet the physical demands of pulleys is questionable; but
      otherwise the veracity of the pulley hypothesis cannot be assessed from the
      structural relations of muscles and fascia bulbi reported.

PMID- 15733304
TI  - Microevolution and development: studies of the genetic basis of adaptive
      variation in insects.

PMID- 15733305
TI  - Genetic variation for dorsal-ventral patterning of the Drosophila melanogaster
      eggshell.
AB  - Patterning of the insect eggshell is an excellent system for exploring the
      molecular basis of phenotypic variation. In Drosophila melanogaster, two dorsal
      anterior respiratory appendages are produced in response to signaling through the
      Epidermal growth factor receptor (Egfr). Previous work implicates Egfr pathway
      function in both intraspecific variation for dorsal appendage spacing (DAS) on
      the eggshell, as well as interspecific differences in dorsal appendage number and
      location. To test the hypothesis that genetic variation in Egfr contributes to
      variation in eggshell patterning, we have made use of naturally occurring
      intraspecific variation for DAS as a model quantitative trait. We found that
      there is substantial segregating genetic variation for DAS in D. melanogaster,
      and have tested for associations with 289 common polymorphisms in the Egfr locus.
      A marginal association was seen with two polymorphic sites in Egfr; however, we
      failed to replicate these findings in a second population, or in a modified
      quantitative complementation test designed to specifically test the effects of
      the putative polymorphisms. Therefore, we conclude that the polymorphisms we have
      identified in Egfr do not contribute to variation in DAS, and further work is
      required to understand the genetic architecture of this trait.

PMID- 15733303
TI  - Palisade endings in extraocular eye muscles revealed by SNAP-25 immunoreactivity.
AB  - Palisade endings form a cuff of nerve terminals around the tip of muscle fibres.
      They are found only in extraocular muscles, but no definite evidence for their
      role in eye movements has been established. Palisade endings have been reported
      in all species so far investigated except the rat. In this study we demonstrate
      that antibodies against SNAP-25, the synaptosomal associated protein of 25 kDa,
      reliably visualize the complete motor, sensory and autonomic innervation of the
      extraocular muscles in human, monkey and rat. The SNAP-25 antibody can be
      combined with other immunofluorescence procedures, and is used here to study
      properties of palisade endings. With SNAP-25 immunolabelling putative palisade
      endings are identified in the rat for the first time. They are not well branched,
      but fulfil several criteria of palisade endings, being associated with non-twitch
      fibres as shown by double labelling with 'myosin heavy chain slow-twitch'
      antibodies. The putative palisade endings of the rat lack alpha-bungarotoxin
      binding, which implies that these synapses are sensory. If palisade endings are
      sensory then they could function as an eye muscle proprioceptor. They seem to be
      a general feature of all vertebrate eye muscles, unlike the other two extraocular
      proprioceptors, muscle spindles and Golgi tendon organs, the presence of which
      varies widely between species.

PMID- 15733306
TI  - Evidence for canalization of Distal-less function in the leg of Drosophila
      melanogaster.
AB  - A considerable body of theory pertaining to the evolution of canalization has
      emerged recently, yet there have been few empirical investigations of their
      predictions. To address this, patterns of canalization and trait correlation were
      investigated under the individual and joint effects of the introgression of a
      loss-of-function allele of the Distal-less gene and high-temperature stress on a
      panel of iso-female lines. Variation was examined for number of sex comb teeth
      and the length of the basi-tarsus on the pro-thoracic leg of male Drosophila
      melanogaster. I demonstrate that whereas there is evidence for trait
      canalization, there is no evidence to support the hypothesis of the evolution of
      genetic canalization as a response to microenvironmental canalization.
      Furthermore, I demonstrate that although there are genetic correlations between
      these traits, there is no association between their measures of canalization. I
      discuss the prospects of the evolutionary lability of the Distal-less gene within
      the context of changes in genetic variation and covariation.

PMID- 15733307
TI  - Generating phenotypic variation: prospects from "evo-devo" research on Bicyclus
      anynana wing patterns.
AB  - Understanding the generation of phenotypic variation is an important challenge
      for modern evolutionary biology, and butterfly wing patterns are an exciting
      system that can shed some light on this issue. Here, we report on recent advances
      in the genetics of Bicyclus anynana butterflies. This system provides the
      potential for a fully integrated study of the evolutionary and developmental
      processes underlying diversity in morphology.

PMID- 15733308
TI  - Jumping genes and AFLP maps: transforming lepidopteran color pattern genetics.
AB  - The color patterns on the wings of lepidopterans are among the most striking
      patterns in nature and have inspired diverse biological hypotheses such as the
      ecological role of aposomatic coloration, the evolution of mimicry, the role of
      human activities in industrial melanism, and the developmental basis of
      phenotypic plasticity. Yet, the developmental mechanisms underlying color pattern
      development are not well understood for three reasons. First, few mutations that
      alter color patterns have been characterized at the molecular level, so there is
      little mechanistic understanding of how mutant phenotypes are produced. Second,
      although gene expression patterns resembling adult color patterns are suggestive,
      there are few data available showing that gene products have a functional role in
      color pattern formation. Finally, because with few exceptions (notably Bombyx),
      genetic maps for most species of Lepidoptera are rudimentary or nonexistent, it
      is very difficult to characterize spontaneous mutants or to determine whether
      mutations with similar phenotypes are because of lesions in the same gene or
      different genes. Discussed here are two strategies for overcoming these
      difficulties: germ-line transformation of lepidopteran species using transposon
      vectors and amplified frequency length polymorphism-based genetic mapping using
      variation between divergent strains within a species or between closely related
      and interfertile species. These advances, taken together, will create new
      opportunities for the characterization of existing genetic variants, the creation
      of new sequence-tagged mutants, and the testing of proposed functional genetic
      relationships between gene products, and will greatly facilitate our
      understanding of the evolution and development of lepidopteran color patterns.

PMID- 15733309
TI  - Both endogenous and environmental factors affect embryo proliferation in the
      polyembryonic wasp Copidosoma floridanum.
AB  - Copidosoma floridanum is a polyembryonic, parasitic wasp of the moth Trichoplusia
      ni. Following oviposition into a host, the C. floridanum egg initially undergoes
      complete (holoblastic) cleavage to form a single morula stage embryo. This embryo
      then undergoes a proliferation phase in which multiple, secondary morulae
      develop. C. floridanum has also evolved a caste system whereby some secondary
      morulae develop into soldier larvae whose function is defense whereas others
      develop into reproductive larvae that become adult wasps. In the current study,
      we conducted manipulative and candidate gene studies to identify factors
      affecting the proliferation phase of C. floridanum development. Transplantation
      of morulae of different ages into different host stages indicated that both
      embryo age and host environment affected the total number of offspring produced
      per morula. Morula age and brood size also significantly affected whether
      offspring of one or both castes were produced in a brood. In contrast, the host
      environment did not significantly affect caste formation. A putative homolog of
      the gene hedgehog (Cf-hh) was partially cloned from C. floridanum. In situ
      hybridization studies indicated that Cf-hh was expressed in secondary morulae
      during the proliferation phase of development, suggesting a possible role for the
      Hh signaling pathway in the evolution of polyembryony.

PMID- 15733310
TI  - Developmental regulation of caste-specific characters in social-insect
      polyphenism.
AB  - Phenotypes of organisms are not determined completely genetically, but vary
      according to environmental factors (phenotypic plasticity). Some organisms
      express several discrete adaptive phenotypes (polyphenism). Social insects
      possess a few types of individuals (castes) in their colonies, to which specific
      tasks are allocated. Here, I review studies on caste polyphenism in ants and
      termites, in terms of the developmental mechanisms of caste-specific characters,
      such as alate wings and soldier mandibles. In ants, the developmental fate of
      caste is probably determined by the pattern-formation genes in the early stage of
      postembryonic development, but apoptotic degeneration occurs in the wing
      primordia of future workers. As apoptotic wing degeneration has been observed in
      two phylogenetically distant groups of ants, this phenomenon is suggested to be
      conserved in many ant species. On the other hand, all termite species possess
      distinct sterile soldiers with specific morphologies suitable for defense. Recent
      studies using molecular techniques isolated genes related to soldier
      differentiation and analyzed the expression profiles of those genes in order to
      understand the mechanism of caste differentiation and the link between molecular
      and social evolution. In this review, I focus on these studies, in terms of the
      alteration of body plan in response to environmental signals, and discuss the
      evolutionary process of the interaction between ontogeny and environment.

PMID- 15733311
TI  - Hoxd13 expression in the developing limbs of the short-tailed fruit bat, Carollia
      perspicillata.
AB  - Bat forelimbs are highly specialized for sustained flight, providing a unique
      model to explore the genetic programs that regulate vertebrate limb diversity.
      Hoxd9-13 genes are important regulators of stylopodium, zeugopodium, and
      autopodium development and thus evolutionary changes in their expression profiles
      and biochemical activities may contribute to divergent limb morphologies in
      vertebrates. We have isolated the genomic region that includes Hoxd12 and Hoxd13
      from Carollia perspicillata, the short-tailed fruit bat. The bat Hoxd13 gene
      encodes a protein that shares 95% identity with human and mouse HOXD13. The
      expression pattern of bat Hoxd13 mRNA during limb development was compared with
      that of mouse. In bat and mouse hindlimbs, the expression patterns of Hoxd13 are
      relatively similar. However, although the forelimb Hoxd13 expression patterns in
      both organisms during early limb bud stages are similar, at later stages they
      diverge; the anterior expression boundary of bat Hoxd13 is posterior-shifted
      relative to the mouse. These findings, compared with the Hoxd13 expression
      profiles of other vertebrates, suggest that divergent Hoxd13 expression patterns
      may contribute to limb morphological variation.

PMID- 15733312
TI  - Anterior localization of maternal mRNAs in a short germ insect lacking bicoid.
AB  - Anterior morphogens have long been postulated to function in early pattern
      formation in several insect taxa. Genetic studies in Drosophila revealed that the
      Bicoid protein performs as such in the fly. Maternally provided bicoid (bcd) mRNA
      is localized at the anterior pole of the oocyte and, upon fertilization, acts as
      the source of a morphogenetic gradient of Bicoid protein. Despite its central
      role in Drosophila, it is believed that bicoid arose rather recently during
      dipteran evolution through duplication of the Hox3 ortholog zen. Here we show
      that in the red flour beetle Tribolium castaneum, RNAs of the homologs of the
      Drosophila transcription factors eagle (Tc'eagle) and pangolin (Tc'pan) are
      maternally localized at the anterior pole of the egg. It is possible that
      underlying mechanisms for the anterior localization of maternal RNAs evolved
      independently in the two clades. However, considering the complexity of the
      process in Drosophila, it is more tempting to speculate that the molecular
      machinery evolved only once during insect evolution. Under this assumption, it
      was present before bicoid evolved as an anterior morphogen. To become
      concentrated at the anterior pole of the egg bicoid may only have had to acquire
      a signal sequence that was recognized by the preexisting localization machinery.
      Although we were not able to demonstrate a function in early embryogenesis for
      Tc'eagle or Tc'pan, our findings suggest that other factors likely function as
      anterior determinants in Tribolium, and other nondipteran insects.

PMID- 15733313
TI  - Developmental organization of the mushroom bodies of Thermobia domestica
      (Zygentoma, Lepismatidae): insights into mushroom body evolution from a basal
      insect.
AB  - The mushroom bodies of the insect brain are sensory integration centers best
      studied for their role in learning and memory. Studies of mushroom body structure
      and development in neopteran insects have revealed conserved morphogenetic
      mechanisms. The sequential production of morphologically distinct intrinsic
      neuron (Kenyon cell) subpopulations by mushroom body neuroblasts and the
      integration of newborn neurons via a discrete ingrowth tract results in an age
      based organization of modular subunits in the primary output neuropil of the
      mushroom bodies, the lobes. To determine whether these may represent ancestral
      characteristics, the present account assesses mushroom body organization and
      development in the basal wingless insect Thermobia domestica. In this insect, a
      single calyx supplied by the progeny of two neuroblast clusters, and three
      perpendicularly oriented lobes are readily identifiable. The lobes are subdivided
      into 15 globular subdivisions (Trauben). Lifelong neurogenesis is observed, with
      axons of newborn Kenyon cells entering the lobes via an ingrowth core. The
      Trauben do not appear progressively during development, indicating that they do
      not represent the ramifications of sequentially produced subpopulations of Kenyon
      cells. Instead, a single Kenyon cell population produces highly branched axons
      that supply all lobe subdivisions. This suggests that although the ground plan
      for neopteran mushroom bodies existed in early insects, the organization of
      modular subunits composed of separate Kenyon cell subpopulations is a later
      innovation. Similarities between the calyx of Thermobia and the highly derived
      fruit fly Drosophila melanogaster also suggest a correlation between calyx
      morphology and Kenyon cell number.

PMID- 15733314
TI  - Expression of Pax group III genes suggests a single-segmental periodicity for
      opisthosomal segment patterning in the spider Cupiennius salei.
AB  - Pair-rule patterning forms a key step for segmentation in insects. The expression
      patterns of pair-rule gene orthologs in representatives of other arthropod groups
      imply that these genes were segmentation genes in the last common ancestor of the
      various arthropod groups, but almost nothing is known about the underlying
      mechanism in noninsect arthropods. Here, we cloned and analyzed members of the
      Pax group III genes from the spider Cupiennius salei. Pax group III genes
      comprise genes like the Drosophila genes paired, gooseberry, and gooseberry
      neuro, as well as the vertebrate Pax 3 and Pax 7 genes. We recovered three Pax
      group III genes from the spider C. salei, Cs-pairberry-1, Cs-pairberry-2, and Cs
      pairberry-3, and show that the combined expression of the three spider genes
      mimics the patterns in insects, suggesting an ancestral role for Pax group III
      genes in segmentation, neurogenesis, and appendage formation in arthropods. One
      of the genes, pairberry-3, is expressed in a segmental periodicity before overt
      morphological segmentation is visible, suggesting a single segmental periodicity
      for opisthosomal segment pattering in the spider. Comparisons among arthropods
      suggest that the underlying mechanisms for pair-rule gene orthologs are more
      diverged than the ones for the segment-polarity genes. We argue that there may be
      a correlation between the lower variation in patterns of segment-polarity genes
      and the phylotypic stage. The segment-polarity genes are required to define the
      segment borders of the embryo at the germ-band stage, the arthropod phylotypic
      stage. Pair-rule gene orthologs act more upstream and may display more variation
      in their action.

PMID- 15733315
TI  - Acute ST-segment elevation myocardial infarction after amoxycillin-induced
      anaphylactic shock in a young adult with normal coronary arteries: a case report.
AB  - BACKGROUND: Acute myocardial infarction (MI) following anaphylaxis is rare,
      especially in subjects with normal coronary arteries. The exact pathogenetic
      mechanism of MI in anaphylaxis remains unclear. CASE PRESENTATION: The case of a
      32-year-old asthmatic male with systemic anaphylaxis, due to oral intake of 500
      mg amoxycillin, complicated by acute ST-elevation MI is the subject of this
      report. Following admission to the local Health Center and almost simultaneously
      with the second dose of subcutaneous epinephrine (0.2 mg), the patient developed
      acute myocardial injury. Coronary arteriography, performed before discharge,
      showed no evidence of obstructive coronary artery disease. In vivo allergological
      evaluation disclosed strong sensitivity to amoxycillin and the minor (allergenic)
      determinants of penicillin. CONCLUSION: Acute ST-elevation MI is a rare but
      potential complication of anaphylactic reactions, even in young adults with
      normal coronary arteries. Coronary artery spasm appears to be the main causative
      mechanism of MI in the setting of "cardiac anaphylaxis". However, on top of the
      vasoactive reaction, a thrombotic occlusion, induced by mast cell-derived
      mediators and facilitated by prolonged hypotension, cannot be excluded as a
      possible contributory factor.

PMID- 15733316
TI  - Comparison of patterns of use, beliefs, and attitudes related to waterpipe
      between beginning and established smokers.
AB  - BACKGROUND: To compare patterns of use, beliefs, and attitudes related to
      waterpipe smoking between university students (beginning smokers) and cafe
      customers (established smokers) in Aleppo Syria, in order to explore the
      evolution of this smoking method. METHODS: Two cross-sectional surveys were
      conducted among representative samples of university students (total 587, 48.4%
      men, mean age 22 years), and waterpipe users among cafe' customers (total 268,
      60% men, mean age 30 years) in Aleppo, Syria. We used interviewer-administered
      questionnaire inquiring about pattern of waterpipe smoking (initiation,
      frequency), situational characteristics of use (partner, place, sharing), beliefs
      related to waterpipe smoking (harmful/addictive properties of waterpipe),
      attitudes related to waterpipe smoking (confidence in quitting, will to quit,
      motivation for quitting, past year quit attempt), and cigarette smoking. RESULTS:
      Daily and regular patterns of smoking become more prevalent with increased
      duration of smoking, but intermittent smoking remains the predominant pattern of
      waterpipe use. Women seem to be drawn later to the habit, which seem to escape
      the usual taboo against women's cigarette smoking. Patterns and context of
      waterpipe use tend to change with progress of the practice affecting frequency,
      setting, and sharing of waterpipe. Unlike beginners, established waterpipe
      smokers seem more smoking-method oriented, more hooked on the habit, less willing
      to quit, and less likely to foresee challenges to quitting. CONCLUSION: Use
      patterns and attitudes related to waterpipe smoking evolve to accommodate the
      change in dependence and life circumstances of the smoker. Most of use features,
      beliefs, attitudes, as well as time-course seem unique to this smoking method
      requiring novel approach to intervention.

PMID- 15733317
TI  - Impact of tetrachloroethylene-contaminated drinking water on the risk of breast
      cancer: using a dose model to assess exposure in a case-control study.
AB  - BACKGROUND: A population-based case-control study was undertaken in 1997 to
      investigate the association between tetrachloroethylene (PCE) exposure from
      public drinking water and breast cancer among permanent residents of the Cape Cod
      region of Massachusetts. PCE, a volatile organic chemical, leached from the vinyl
      lining of certain water distribution pipes into drinking water from the late
      1960s through the early 1980s. The measure of exposure in the original study,
      referred to as the relative delivered dose (RDD), was based on an amount of PCE
      in the tap water entering the home and estimated with a mathematical model that
      involved only characteristics of the distribution system. METHODS: In the current
      analysis, we constructed a personal delivered dose (PDD) model that included
      personal information on tap water consumption and bathing habits so that
      inhalation, ingestion, and dermal absorption were also considered. We reanalyzed
      the association between PCE and breast cancer and compared the results to the
      original RDD analysis of subjects with complete data. RESULTS: The PDD model
      produced higher adjusted odds ratios than the RDD model for exposures > 50th and
      >75th percentile when shorter latency periods were considered, and for exposures
      < 50th and >90th percentile when longer latency periods were considered. Overall,
      however, the results from the PDD analysis did not differ greatly from the RDD
      analysis. CONCLUSION: The inputs that most heavily influenced the PDD model were
      initial water concentration and duration of exposure. These variables were also
      included in the RDD model. In this study population, personal factors like bath
      and shower temperature, bathing frequencies and durations, and water consumption
      did not differ greatly among subjects, so including this information in the model
      did not significantly change subjects' exposure classification.

PMID- 15733318
TI  - Genome wide analysis of Arabidopsis core promoters.
AB  - BACKGROUND: Core promoters are the gene regulatory regions most proximal to the
      transcription start site (TSS), central to the formation of pre-initiation
      complexes and for combinatorial gene regulation. The DNA elements required for
      core promoter function in plants are poorly understood. To establish the sequence
      motifs that characterize plant core promoters and to compare them to the
      corresponding sequences in animals, we took advantage of available full-length
      cDNAs (FL-cDNAs) and predicted upstream regulatory sequences to carry out the
      analysis of 12,749 Arabidopsis core promoters. RESULTS: Using a combination of
      expectation maximization and Gibbs sampling methods, we identified several motifs
      overrepresented in Arabidopsis core promoters. One of them corresponded to the
      TATA element, for which an in-depth analysis resulted in the generation of robust
      TATA Nucleotide Frequency Matrices (NFMs) capable of predicting Arabidopsis TATA
      elements with a high degree of confidence. We established that approximately 29%
      of all Arabidopsis promoters contain TATA motifs, clustered around position -32
      with respect to the TSS. The presence of TATA elements was associated with genes
      represented more frequently in EST collections and with shorter 5' UTRs. No cis
      elements were found over-represented in TATA-less, compared to TATA-containing
      promoters. CONCLUSION: Our studies provide a first genome-wide illustration of
      the composition and structure of core Arabidopsis promoters. The percentage of
      TATA-containing promoters is much lower than commonly recognized, yet comparable
      to the number of Drosophila promoters containing a TATA element. Although several
      other DNA elements were identified as over-represented in Arabidopsis promoters,
      they are present in only a small fraction of the genes and they represent
      elements not previously described in animals, suggesting a distinct architecture
      of the core promoters of plant and animal genes.

PMID- 15733319
TI  - Canavanine-induced longevity in mice may require diets with greater than 15.7%
      protein.
AB  - BACKGROUND: Dietary administration of 1% canavanine had been shown to improve
      survival in female BALB/c mice consuming diets containing 23.4% protein (dry
      matter basis). METHODS: In order to determine if this effect also obtains at more
      moderate dietary protein concentrations, 30 female BALB/c mice were fed a basal
      diet with 14% protein (15.7% dry matter basis) and another 30 were fed the same
      diet plus 1% canavanine. RESULTS: Neither mean (Control 873.2 d, Canavanine 870.0
      d; SEM = 34.2 d; P = 0.949 from ANOVA) nor median (Control 902 d, Canavanine
      884.5 d; P = 0.9058 from Mann-Whitney) lifespans differed between groups.Although
      mean antinuclear antibody (ANA) titers did not differ between control and
      canavanine-treated mice at 833 days of age (19.84 vs 20.39 respectively; SEM =
      2.64; P = 0.889 from ANOVA), one canavanine-treated mouse displayed an outlying
      ANA value of 50 (next lower value = 30) denoting possible early sign of incipient
      autoimmune disease in that individual. CONCLUSION: There may be an interaction
      between dietary protein level and canavanine with respect to lifespan in mice.

PMID- 15733321
TI  - Astrocyte production of the chemokine macrophage inflammatory protein-2 is
      inhibited by the spice principle curcumin at the level of gene transcription.
AB  - BACKGROUND: In neuropathological processes associated with neutrophilic
      infiltrates, such as experimental allergic encephalitis and traumatic injury of
      the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is
      thought to play a pivotal role in the induction and perpetuation of inflammation
      in the central nervous system (CNS). The origin of MIP-2 in inflammatory
      disorders of the brain has not been fully defined but astrocytes appear to be a
      dominant source of this chemokine.Curcumin is a spice principle in, and
      constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and
      antioxidant activities suggest that it might be a useful adjunct in the treatment
      of neurodegenerative illnesses characterized by inflammation. Relatively
      unexplored, but relevant to its potential therapeutic efficacy in
      neuroinflammatory syndromes is the effect of curcumin on chemokine production. To
      examine the possibility that curcumin may influence CNS inflammation by
      mechanisms distinct from its known anti-oxidant activities, we studied the effect
      of this spice principle on the synthesis of MIP-2 by astrocytes. METHODS: Primary
      astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were
      stimulated with lipopolysaccharide in the presence or absence of various amount
      of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi
      quantitative PCR and MIP-2 protein production in the culture supernatants was
      quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct,
      pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of
      curcumin. RESULTS: The induction of MIP-2 gene expression and the production of
      MIP-2 protein were inhibited by curcumin. Curcumin also inhibited
      lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene
      construct in primary astrocytes. However MIP-2 gene induction by
      lipopolysaccharide was not inhibited by another anti-oxidant, epigallocatechin
      gallate. CONCLUSION: Our results indicate that curcumin potently inhibits MIP-2
      production at the level of gene transcription and offer further support for its
      potential use in the treatment of inflammatory conditions of the CNS.

PMID- 15733322
TI  - Advances in wearable technology and applications in physical medicine and
      rehabilitation.
AB  - The development of miniature sensors that can be unobtrusively attached to the
      body or can be part of clothing items, such as sensing elements embedded in the
      fabric of garments, have opened countless possibilities of monitoring patients in
      the field over extended periods of time. This is of particular relevance to the
      practice of physical medicine and rehabilitation. Wearable technology addresses a
      major question in the management of patients undergoing rehabilitation, i.e. have
      clinical interventions a significant impact on the real life of patients?
      Wearable technology allows clinicians to gather data where it matters the most to
      answer this question, i.e. the home and community settings. Direct observations
      concerning the impact of clinical interventions on mobility, level of
      independence, and quality of life can be performed by means of wearable systems.
      Researchers have focused on three main areas of work to develop tools of clinical
      interest: 1)the design and implementation of sensors that are minimally obtrusive
      and reliably record movement or physiological signals, 2)the development of
      systems that unobtrusively gather data from multiple wearable sensors and deliver
      this information to clinicians in the way that is most appropriate for each
      application, and 3)the design and implementation of algorithms to extract
      clinically relevant information from data recorded using wearable technology.
      Journal of NeuroEngineering and Rehabilitation has devoted a series of articles
      to this topic with the objective of offering a description of the state of the
      art in this research field and pointing to emerging applications that are
      relevant to the clinical practice in physical medicine and rehabilitation.

PMID- 15733320
TI  - Do malaria ookinete surface proteins P25 and P28 mediate parasite entry into
      mosquito midgut epithelial cells?
AB  - BACKGROUND: P25 and P28 are related ookinete surface proteins highly conserved
      throughout the Plasmodium genus that are under consideration as candidates for
      inclusion in transmission-blocking vaccines. Previous research using transgenic
      rodent malaria parasites lacking P25 and P28 has demonstrated that these proteins
      have multiple partially redundant functions during parasite infection of the
      mosquito vector, including an undefined role in ookinete traversal of the
      mosquito midgut epithelium, and it has been suggested that, unlike wild-type
      parasites, Dko P25/P28 parasites migrate across the midgut epithelium via an
      intercellular, rather than intracellular, route. PRESENTATION OF THE HYPOTHESIS:
      This paper presents an alternative interpretation for the previous observations
      of Dko P25/P28 parasites, based upon a recently published model of the route of
      ookinete invasion across the midgut epithelium. This model claims ookinete
      invasion is intracellular, with entry occurring through the lateral apical plasma
      membrane of midgut epithelial cells, and is associated with significant
      invagination of the midgut epithelium localised at the site of parasite
      penetration. Following this model, it is hypothesized that: (1) a sub-population
      of Dko P25/P28 ookinetes invaginate, but do not penetrate, the apical surface of
      the midgut epithelium and thus remain within the midgut lumen; and (2) another
      sub-population of Dko P25/P28 parasites successfully enters and migrates across
      the midgut epithelium via an intracellular route similar to wild-type parasites
      and subsequently develops into oocysts. TESTING THE HYPOTHESIS: These hypotheses
      are tested by showing how they can account for previously published observations
      and incorporate them into a coherent and consistent explanatory framework. Based
      upon these hypotheses, several quantitative predictions are made, which can be
      experimentally tested, about the relationship between the densities of invading
      Dko P25/P28 ookinetes in different regions of the midgut epithelium and the
      number of oocyst stage parasites to which these mutant ookinetes give rise.
      IMPLICATIONS OF THE HYPOTHESIS: The recently published model of ookinete invasion
      implies that Dko P25/P28 parasites are greatly, although not completely, impaired
      in their ability to enter the midgut epithelium. Therefore, P25 and/or P28 have a
      novel, previously unrecognized, function in mediating ookinete entry into midgut
      epithelial cells, suggesting that one mode of action of transmission-blocking
      antibodies to these ookinete surface proteins is to inhibit this function.

PMID- 15733323
TI  - Abdominal surgical site infections: incidence and risk factors at an Iranian
      teaching hospital.
AB  - BACKGROUND: Abdominal surgical site infections are among the most common
      complications of inpatient admissions and have serious consequences for outcomes
      and costs. Different risk factors may be involved, including age, sex, nutrition
      and immunity, prophylactic antibiotics, operation type and duration, type of
      shaving, and secondary infections. This study aimed to determine the risk factors
      affecting abdominal surgical site infections and their incidence at Imam
      Khomeini, a major referral teaching hospital in Iran. METHODS: Patients (n = 802)
      who had undergone abdominal surgery were studied and the relationships among
      variables were analyzed by Student's t and Chi-square tests. The subjects were
      followed for 30 days and by a 20-item questionnaire. Data were collected through
      pre- and post-operative examinations and telephone follow-ups. RESULTS: Of the
      802 patients, 139 suffered from SSI (17.4%). In 40.8% of the cases, the wound was
      dirty infected. The average age for the patients was 46.7 years. The operations
      were elective in 75.7% of the cases and 24.7% were urgent. The average duration
      of the operation was 2.24 hours, the average duration of pre-operative hospital
      stay 4.31 days and the average length of (pre- and post-operation) hospital stay
      11.2 days. Three quarters of the cases were shaved 12 hours before the operation.
      The increased operation time, increased bed stay, electivity of the operation,
      septicity of the wound, type of incision, the administration of prophylactic
      antibiotic, type of operation, background disease, and the increased time lapse
      between shaving and operation all significantly associated with SSI with a p
      value less than 0.001. CONCLUSION: In view of the high rate of SSI reported here
      (17.4% compared with the 14% quoted in literature), this study suggests that by
      reducing the average operation time to less than 2 hours, the average
      preoperative stay to 4 days and the overall stay to less than 11 days, and
      approximating the timing of shaving to the operation and substituting cefazolin
      for cefaluthin when prophylactic antibiotic is to be administered, the SSI may be
      reduced to a more acceptable level.

PMID- 15733324
TI  - Effects of prostaglandin E2 on the electrical properties of thermally classified
      neurons in the ventromedial preoptic area of the rat hypothalamus.
AB  - BACKGROUND: Physiological and morphological evidence suggests that activation of
      the ventromedial preoptic area of the hypothalamus (VMPO) is an essential
      component of an intravenous LPS-dependent fever. In response to the endogenous
      pyrogen prostaglandin E2 (PGE2), the majority of temperature insensitive neurons
      in the VMPO show an increase in firing rate, while warm sensitive neurons are
      inhibited. We have hypothesized that these PGE2 dependent effects on firing rate
      are due to changes in the inherent electrical properties of VMPO neurons, which
      are regulated by the activity of specific ionic currents. RESULTS: To
      characterize the electrical properties of VMPO neurons, whole-cell recordings
      were made in tissue slices from male Sprague-Dawley rats. Our results indicate
      that PGE2 dependent firing rate responses were not the result of changes in
      resting membrane potential, action potential amplitude and duration, or local
      synaptic input. However, PGE2 reduced the input resistance of all VMPO neurons,
      while increasing the excitability of temperature insensitive neurons and
      decreasing the excitability of warm sensitive neurons. In addition, the majority
      of temperature insensitive neurons responded to PGE2 with an increase in the rate
      of rise of the depolarizing prepotential that precedes each action potential.
      This response to PGE2 was reversed for warm sensitive neurons, in which the
      prepotential rate of rise decreased. CONCLUSION: We would therefore suggest that
      PGE2 is having an effect on the ionic currents that regulate firing rate by
      controlling how fast membrane potential rises to threshold during the
      prepotential phase of the action potential.

PMID- 15733325
TI  - Presence of factors that activate platelet aggregation in mitral stenotic
      patients' plasma.
AB  - BACKGROUND: Although the association between mitral stenosis (MS) and increased
      coagulation activity is well recognized, it is unclear whether enhanced
      coagulation remains localized in the left atrium or whether this represents a
      systemic problem. To assess systemic coagulation parameters and changes in
      platelet aggregation, we measured fibrinogen levels and performed in vitro
      platelet function tests in plasma obtained from mitral stenotic patients' and
      from healthy control subjects' peripheral venous blood. METHODS: Sixteen newly
      diagnosed patients with rheumatic MS (Group P) and 16 healthy subjects (Group N)
      were enrolled in the study. Platelet-equalized plasma samples were evaluated to
      determine in vitro platelet function, using adenosine diphosphate (ADP), collagen
      and epinephrine in an automated aggregometer. In vitro platelet function tests in
      group N were performed twice, with and without plasma obtained from group P.
      RESULTS: There were no significant differences between the groups with respect to
      demographic variables. Peripheral venous fibrinogen levels in Group P were not
      significantly different from those in Group N. Adenosine diphosphate, epinephrine
      and collagen-induced platelet aggregation ratios were significantly higher in
      Group P than in Group N. When plasma obtained from Group P was added to Group N
      subjects' platelets, ADP and collagen-induced, but not epinephrine-induced,
      aggregation ratios were significantly increased compared to baseline levels in
      Group N. CONCLUSION: Platelet aggregation is increased in patients with MS, while
      fibrinogen levels remain similar to controls. We conclude that mitral stenotic
      patients exhibit increased systemic coagulation activity and that plasma
      extracted from these patients may contain some transferable factors that activate
      platelet aggregation.

PMID- 15733326
TI  - Determinants of health insurance ownership among South African women.
AB  - BACKGROUND: Studies conducted in developed countries using economic models show
      that individual- and household- level variables are important determinants of
      health insurance ownership. There is however a dearth of such studies in sub
      Saharan Africa. The objective of this study was to examine the relationship
      between health insurance ownership and the demographic, economic and educational
      characteristics of South African women. METHODS: The analysis was based on data
      from a cross-sectional national household sample derived from the South African
      Health Inequalities Survey (SANHIS). The study subjects consisted of 3,489 women,
      aged between 16 and 64 years. It was a non-interventional, qualitative response
      econometric study. The outcome measure was the probability of a respondent's
      ownership of a health insurance policy. RESULTS: The chi2 test for goodness of
      fit indicated satisfactory prediction of the estimated logit model. The
      coefficients of the covariates for area of residence, income, education,
      environment rating, age, smoking and marital status were positive, and all
      statistically significant at p < or = 0.05. Women who had standard 10 education
      and above (secondary), high incomes and lived in affluent provinces and permanent
      accommodations, had a higher likelihood of being insured. CONCLUSION: Poverty
      reduction programmes aimed at increasing women's incomes in poor provinces;
      improving living environment (e.g. potable water supplies, sanitation,
      electricity and housing) for women in urban informal settlements; enhancing
      women's access to education; reducing unemployment among women; and increasing
      effective coverage of family planning services, will empower South African women
      to reach a higher standard of living and in doing so increase their economic
      access to health insurance policies and the associated health services.

PMID- 15733327
TI  - GC-compositional strand bias around transcription start sites in plants and
      fungi.
AB  - BACKGROUND: A GC-compositional strand bias or GC-skew (=(C-G)/(C+G)), where C and
      G denote the numbers of cytosine and guanine residues, was recently reported near
      the transcription start sites (TSS) of Arabidopsis genes. However, it is unclear
      whether other eukaryotic species have equally prominent GC-skews, and the
      biological meaning of this trait remains unknown. RESULTS: Our study confirmed a
      significant GC-skew (C > G) in the TSS of Oryza sativa (rice) genes. The full
      length cDNAs and genomic sequences from Arabidopsis and rice were compared using
      statistical analyses. Despite marked differences in the G+C content around the
      TSS in the two plants, the degrees of bias were almost identical. Although slight
      GC-skew peaks, including opposite skews (C < G), were detected around the TSS of
      genes in human and Drosophila, they were qualitatively and quantitatively
      different from those identified in plants. However, plant-like GC-skew in regions
      upstream of the translation initiation sites (TIS) in some fungi was identified
      following analyses of the expressed sequence tags and/or genomic sequences from
      other species. On the basis of our dataset, we estimated that > 70 and 68% of
      Arabidopsis and rice genes, respectively, had a strong GC-skew (> 0.33) in a 100
      bp window (that is, the number of C residues was more than double the number of G
      residues in a +/-100-bp window around the TSS). The mean GC-skew value in the TSS
      of highly-expressed genes in Arabidopsis was significantly greater than that of
      genes with low expression levels. Many of the GC-skew peaks were preferentially
      located near the TSS, so we examined the potential value of GC-skew as an index
      for TSS identification. Our results confirm that the GC-skew can be used to
      assist the TSS prediction in plant genomes. CONCLUSION: The GC-skew (C > G)
      around the TSS is strictly conserved between monocot and eudicot plants (ie.
      angiosperms in general), and a similar skew has been observed in some fungi.
      Highly-expressed Arabidopsis genes had overall a more marked GC-skew in the TSS
      compared to genes with low expression levels. We therefore propose that the GC
      skew around the TSS in some plants and fungi is related to transcription. It
      might be caused by mutations during transcription initiation or the frequent use
      of transcription factor-biding sites having a strand preference. In addition, GC
      skew is a good candidate index for TSS prediction in plant genomes, where there
      is a lack of correlation among CpG islands and genes.

PMID- 15733328
TI  - Volume-based non-continuum modeling of bone functional adaptation.
AB  - BACKGROUND: Bone adapts to mechanical strain by rearranging the trabecular
      geometry and bone density. The common finite element methods used to simulate
      this adaptation have inconsistencies regarding material properties at each node
      and are computationally demanding. Here, a volume-based, non-continuum
      formulation is proposed as an alternative. Adaptive processes corresponding to
      various external mechanical loading conditions are simulated for the femur.
      RESULTS: Bone adaptations were modeled for one-legged stance, abduction and
      adduction. One-legged stance generally results in higher bone densities than the
      other two loading cases. The femoral head and neck are the regions where
      densities change most drastically under different loading conditions while the
      distal area always contains the lowest densities regardless of the loading
      conditions. In the proposed formulation, the inconsistency of material densities
      or strain energy densities, which is a common problem to finite element based
      approaches, is eliminated. The computational task is alleviated through
      introduction of the quasi-binary connectivity matrix and linearization operations
      in the Jacobian matrix and is therefore computationally less demanding.
      CONCLUSION: The results demonstrated the viability of the proposed formulation to
      study bone functional adaptation under mechanical loading.

PMID- 15733329
TI  - Diabetic neuropathies. Classification, clinical features, and pathophysiological
      basis.
AB  - Diabetes mellitus is associated with a wide spectrum of neuropathy syndromes,
      ranging from a mild asymptomatic distal sensory neuropathy to a severe disabling
      radiculoplexus neuropathy. As the pathophysiology of these separate conditions is
      better understood, classification of the various phenotypes becomes important
      because of treatment implications. Here we provide a short summary of the history
      of the classification of diabetic neuropathies and try to describe the most
      common forms classified according to their presumed pathophysiology. We have
      tried to include epidemiological data where available, as well as histopathology
      of nerve in several diabetic neuropathies.

PMID- 15733330
TI  - Neuro-Behcet disease. A review.
AB  - BACKGROUND: Behcet disease is a vasculitis with mucocutaneous, ocular, arthritic,
      vascular, and other manifestations. Its neurologic manifestations (neuro-Behcet
      disease) are relatively rare, but they must be thoroughly investigated due to
      their grave prognosis. REVIEW SUMMARY: The frequency of neurologic
      manifestations, more common in male Behcet patients, is between 5% and 30%. Both
      the central and peripheral nervous systems can be involved. Central nervous
      system manifestations can be divided into 2 main groups: (1) parenchymal
      involvement, which includes brainstem involvement, hemispheric manifestations,
      spinal cord lesions, and meningoencephalitic presentations; (2) nonparenchymal
      involvement, including dural sinus thrombosis, arterial occlusion, and/or
      aneurysms. Peripheral neuropathy and myopathy are relatively rare. Cerebrospinal
      fluid analysis reveals pleocytosis and elevated protein levels. Magnetic
      resonance imaging is the investigation of choice which often reveals iso
      /hypointense lesions in T1-weighted images and hyperintense lesions in T2
      weighted images, mostly in the mesodiencephalic junction, cerebellar peduncles,
      and other parts of the brainstem. Corticosteroids and adjuvant immunosuppressive
      therapy are used for parenchymal manifestations, and corticosteroids and
      anticoagulants are used for treatment of dural sinus thrombosis. CONCLUSION:
      Neuro-Behcet disease must be considered in the differential diagnosis of stroke
      in young adults, multiple sclerosis, movement disorders, intracranial
      hypertension, intracranial sinovenous occlusive diseases, and other neurologic
      syndromes.

PMID- 15733331
TI  - The primary parasomnias. A review for neurologists.
AB  - BACKGROUND: Primary parasomnias are undesirable motor or verbal phenomena which
      occur during sleep and result in abnormal arousals. They occur out of all sleep
      stages or during transitions between sleep and awake. Secondary parasomnias are
      sleep disturbances that are caused by disorders of other organ systems. This
      review addresses only primary parasomnias. Arousal disorders and the parasomnias
      associated with REM sleep are the primary parasomnias most likely to be seen in a
      neurology practice. Sleep-wake transition disorders are also discussed with
      nocturnal leg cramps, probably the most common in this group. REVIEW SUMMARY: The
      salient clinical features of the primary parasomnias are discussed. Emphasis is
      placed on the differential diagnosis of the different conditions and the best
      management strategies. Parasomnias encountered in infancy, such as infant sleep
      apnea, are not discussed in this review. CONCLUSIONS: Parasomnias are common
      disturbances of sleep that may significantly affect the patient's quality of life
      and that of the bed partner. Most parasomnias can be diagnosed with careful
      history taking and polysomnography, and management is usually safe and effective.

PMID- 15733332
TI  - Binocular diplopia. A practical approach.
AB  - BACKGROUND: Diplopia is a common complaint in both inpatient and outpatient
      neurologic practice. Its causes are many, and special historical and examination
      features are important to localization and accurate diagnosis. REVIEW SUMMARY:
      This review is divided into 2 sections: the first related to diagnosis and the
      second to treatment of binocular diplopia. In the diagnostic section, emphasis is
      placed on identification of historical and examination features that can help to
      differentiate diplopia caused by dysfunction of cranial nerves versus
      neuromuscular junction, or orbital extraocular muscle. Techniques available to
      the neurologist for examining ocular motility and ocular misalignment and focused
      laboratory testing to evaluate diplopia are discussed in detail. The final
      section covers the various treatments for binocular diplopia, with
      recommendations regarding the utility of each treatment for different types of
      diplopia. CONCLUSIONS: A logical step-by-step approach applied to each patient
      with diplopia will help prevent misdiagnosis and improve patient care.

PMID- 15733333
TI  - Chronic neuropathic pain. Mechanisms, diagnosis, and treatment.
AB  - BACKGROUND: The management of chronic pain represents a significant public health
      issue in the United States. It is both costly to our health care system and
      devastating to the patient's quality of life. The need to improve pain outcomes
      is reflected by the congressional declaration of the present decade as the
      "Decade of Pain Control and Research," and the acknowledgment in January 2001 of
      pain as the "fifth vital sign" by the Joint Commission of Healthcare
      Organizations. REVIEW SUMMARY: At present, therapeutic options are largely
      limited to drugs approved for other conditions, including anticonvulsants,
      antidepressants, antiarrhythmics, and opioids. However, treatment based on the
      underlying disease state (eg, postherpetic neuralgia, diabetic neuropathy) may be
      less than optimal, in that 2 patients with the same neuropathic pain syndrome may
      have different symptomatology and thus respond differently to the same treatment.
      Increases in our understanding of the function of the neurologic system over the
      last few years have led to new insights into the mechanisms underlying pain
      symptoms, especially chronic and neuropathic pain. CONCLUSIONS: The rapidly
      evolving symptom- and mechanism-based approach to the treatment of neuropathic
      pain holds promise for improving the quality of life of our patients with
      neuropathic pain.

PMID- 15733334
TI  - Recombinant tissue plasminogen activator (rtPA) for stroke. The perspective at 8
      years.
AB  - OBJECTIVE: To review the 8-year experience with recombinant tissue plasminogen
      activator (rtPA) for stroke, with commentary on ramifications for the approach to
      stroke treatment, directions in stroke research, and sociological aspects of
      stroke as a disease of concern in our society. BACKGROUND: Approved in 1996, rtPA
      remains the only drug indicated for the treatment of ischemic stroke. Stroke
      treatment and research have evolved rapidly in response to opportunities and
      discoveries related to the advent of rtPA. The presence of rtPA has engendered an
      increased level of awareness about all aspects of stroke. METHODOLOGY: Literature
      review was performed, focusing on topics that in the author's view are of
      greatest relevance to the use of rtPA in clinical practice and to the directions
      in which the presence of rtPA is moving the field of stroke treatment, research,
      and politics. RESULTS: Challenges have been raised, and met, regarding the
      validity of the data upon which the approval for rtPA was based. Limitations in
      the use of rtPA include the brief time available for treatment, the need for
      rapid imaging and blood-pressure control, and the fact that large-artery
      occlusions respond poorly. The major risk of treatment is brain hemorrhage, and
      although predictors of hemorrhage are known, their presence does not constitute
      an absolute contraindication to treatment. A virtual subindustry has evolved to
      enhance the benefit and applicability of rtPA through refined imaging technology
      and the use of rtPA intra-aterially, as well as in combination with other agents
      and devices. Sociopolitically, rtPA has elevated the level of awareness of stroke
      and provided impetus for the stroke center movement and federal legislation to
      stop stroke. CONCLUSION: The development of rtPA has been the most effective
      advance in the field of stroke. It has generated healthy debate regarding the
      design, performance, and interpretation of stroke trials, including cost-benefit
      considerations. rtPA has stimulated research in a multitude of areas, enhanced
      our understanding of stroke pathophysiology, and defined important limits and
      risks for urgent intervention. rtPA is the cornerstone of the stroke center
      movement, as well as legislation in behalf of stroke at the congressional level.

PMID- 15733335
TI  - Patient and family fact sheet. Current treatments for multiple sclerosis.

PMID- 15733336
TI  - Activation of mGluR5 modulates Ca2+ currents in retinal amacrine cells from the
      chick.
AB  - In the inner plexiform layer, amacrine cells receive glutamatergic input from
      bipolar cells. Glutamate can depolarize amacrine cells by activation of
      ionotropic glutamate receptors or mediate potentially more diverse changes via
      activation of G protein-coupled metabotropic glutamate receptors (mGluR5). Here,
      we asked whether selective activation of metabotropic glutamate receptor 5 is
      linked to modulation of the voltage-gated Ca2+ channels expressed by cultured
      GABAergic amacrine cells. To address this, we performed whole-cell voltage clamp
      experiments, primarily in the perforated-patch configuration. We found that
      agonists selective for mGluR5, including (RS)-2-chloro-5-hydroxyphenylglycine
      (CHPG), enhanced the amplitude of the voltage-dependent Ca2+ current. The voltage
      dependent Ca2+ current and CHPG-dependent current enhancement were blocked by
      nifedipine, indicating that L-type Ca2+ channels, specifically, were being
      modulated. We have previously shown that activation of mGluR5 produces Ca2+
      elevations in cultured amacrine cells (Sosa et al., 2002). Loading the cells with
      5 mM BAPTA inhibited the mGluR5-dependent enhancement, suggesting that the
      cytosolic Ca2+ elevations are required for modulation of the current. Although
      activation of mGluR5 is typically linked to activation of protein kinase C, we
      found that direct activation of this kinase leads to inhibition of the Ca2+
      current, indicating that stimulation of this enzyme is not responsible for the
      mGluR5-dependent enhancement. Interestingly, direct stimulation of protein kinase
      A produced an enhancement of the Ca2+ current similar to that observed with
      activation of mGluR5. Thus, activation of mGluR5 may modulate the L-type voltage
      gated Ca2+ current in these GABAergic amacrine cells via activation of protein
      kinase A, possibly via direct activation of a Ca2(+)-dependent adenylate cyclase.

PMID- 15733337
TI  - Synaptic organization of GABAergic amacrine cells in the salamander retina.
AB  - The synaptic organization of GABA-immunoreactive (GABA-IR) amacrine cells in the
      inner plexiform layer (IPL) of salamander retina was studied with the use of
      postembedding immuno-electron microscopy. A total of 457 GABA-IR amacrine
      synapses, with identified postsynaptic elements, were analyzed on photomontages
      of electron micrographs covering 3,618 microm2 of the IPL. GABA-IR amacrine
      synapses were distributed throughout the IPL, with a small peak at the proximal
      margin of sublamina a. The majority of the output targets (81%) were GABA(-)
      neurons. Most of the contacts were simple synapses with one postsynaptic element
      identified as a process of an amacrine cell (55%), bipolar cell (19%) or ganglion
      cell (26%), and serial synapses were very rare. Of the 89 postsynaptic bipolar
      terminals, 63% participated in a reciprocal feedback synapse with the same
      presynaptic GABA-IR amacrine profile. There appeared to be no preference between
      GABA-IR amacrine contacts with rod- or cone-dominated bipolar cells (9.1% vs.
      8.9%) or in the total number of amacrine synapses in sublaminas a and b (52% vs.
      47%). The preponderance of amacrine cell input to bipolar cells in the OFF layer
      was derived from GABA-IR cells. These findings provide ultrastructural support to
      the existing physiological studies regarding the functional roles of the
      GABAergic amacrine cells in this species. Our results have added to the data base
      demonstrating that, in contrast to mammals, GABA-IR amacrine cells in amphibians
      and other nonmammals contact other amacrine cells more frequently, suggesting
      greater involvement of GABAergic amacrine cells in modulating lateral inhibitory
      pathways.

PMID- 15733338
TI  - Photopigment optical density of the human foveola and a paradoxical senescent
      increase outside the fovea.
AB  - Photopigment optical density (OD) of middle-(M) and long-(L) wavelength-sensitive
      cones was determined to evaluate the hypothesis that reductions in the amount of
      photopigment are responsible for age-dependent sensitivity losses of the human
      cone pathways. Flicker thresholds were measured at the peak and tail of the
      photoreceptor's absorption spectrum as a function of the intensity of a bleaching
      background. Photopigment OD was measured at 0 (fovea), 2, 4, and 8 deg in the
      temporal retina by use of a 0.3-deg-diameter test spot. Seventy-two genetically
      characterized dichromats were studied so that the L- and M-cones could be
      analyzed separately. Subjects included 28 protanopes with M- but no L-cones and
      44 deuteranopes with L- but no M-cones (all male, age range 12-29 and 55-83
      years). Previous methods have not provided estimates of photopigment OD for
      separate cone classes in the foveola. In this study, it was found that foveolar
      cones are remarkably efficient, absorbing 78% of the available photons (OD =
      0.65). Photopigment OD decreased exponentially with retinal eccentricity
      independently of age and cone type. Paradoxically, the OD of perifoveal cones
      increased significantly with age. Over the 70-year age range of our participants,
      the perifoveal M- and L-cones showed a 14% increase in capacity to absorb photons
      despite a 30% decrease in visual sensitivity over the same period.

PMID- 15733339
TI  - Voltage-clamp analysis and computational model of dopaminergic neurons from mouse
      retina.
AB  - Isolated dopaminergic amacrine (DA) cells in mouse retina fire rhythmic,
      spontaneous action potentials and respond to depolarizing current with trains of
      low-frequency action potentials. To investigate the roles of voltage-gated ion
      channels in these processes, the transient A-type K+ current (I(K,A)) and Ca2+
      current (I(Ca)) in isolated mouse DA cells were analyzed by voltage clamp. The
      I(K,A) activated at -60 mV and inactivated rapidly. I(Ca) activated at around -30
      mV and reached a peak at 10 mV without apparent inactivation. We also extended
      our previous computational model of the mouse DA cell to include the new
      electrophysiological data. The model consisted of a membrane capacitance in
      parallel with eight currents: Na+ transient (I(Na,T)), Na+ persistent (I(Na,P)),
      delayed rectifier potassium (I(Kdr)), I(K,A), calcium-dependent potassium
      (I(K,Ca)), L-type Ca2+ I(Ca), hyperpolarization-activated cation current (I(h)),
      and a leak current (I(L)). Hodgkin-Huxley type equations were used to define the
      voltage- and time-dependent activation and inactivation. The simulations were
      implemented using the neurosimulator SNNAP. The model DA cell was spontaneously
      active from a wide range of initial membrane potentials. The spontaneous action
      potentials reached 35 mV at the peak and hyperpolarized to -76 mV between spikes.
      The spontaneous firing frequency in the model was 6 Hz. The model DA cell
      responded to prolonged depolarizing current injection by increasing its spiking
      frequency and eventually reaching a depolarization block at membrane potentials
      greater than -10 mV. The most important current for determining the firing rate
      was I(K,A). When the amplitude of I(K,A) was decreased, the firing rate
      increased. I(Ca) and I(K,Ca) also affected the width of action potentials but had
      only minor effects on the firing rate. Ih affected the firing rate slightly but
      did not change the waveform of the action potentials.

PMID- 15733340
TI  - Development of sensitivity to visual motion in macaque monkeys.
AB  - The development of spatial vision is relatively well documented in human and
      nonhuman primates. However, little is known about the development of sensitivity
      to motion. We measured the development of sensitivity to direction of motion, and
      the relationship between motion and contrast sensitivity in macaque monkeys as a
      function of age. Monkeys (Macaca nemestrina, aged between 10 days and 3 years)
      discriminated direction of motion in random-dot kinematograms. The youngest
      monkeys showed directionally selective orienting and the ability to integrate
      motion signals at large dot displacements and fast speeds. With age, coherence
      sensitivity improved for all spatial and temporal dot displacements tested. The
      temporal interval between the dots was far less important than the spatial offset
      in determining the animals' performance at all but the youngest ages. Motion
      sensitivity improved well beyond the end of the first postnatal year, when mid
      spatial-frequency contrast sensitivity reached asymptote, and continued for at
      least 3 years. Sensitivity to contrast at high spatial frequencies also continued
      to develop beyond the end of the first year. We conclude that the development of
      motion sensitivity depends on mechanisms beyond the low-level filters presumed to
      limit acuity and contrast sensitivity, and most likely reflects the function of
      extrastriate visual areas.

PMID- 15733341
TI  - MLA-sensitive cholinergic receptors involved in the detection of complex moving
      stimuli in retina.
AB  - Acetylcholine, acting through nicotinic acetylcholine receptors, mediates the
      response properties of many ganglion cells in the rabbit retina, including those
      that are directionally selective (DS; Ariel & Daw, 1982a, b). For example,
      Grzywacz et al. (1998) showed that cholinergic input is necessary for DS
      responses to drifting gratings, a form of textured stimulus. However, the
      identities and locations of the neuronal acetylcholine receptor (nAChR) subtypes
      that mediate this input are not clear (Keyser et al., 2000). We investigated the
      role of methyllycaconitine-sensitive, alpha7-like nAChRs in mediating DS
      responses to textured stimuli and apparent motion. We recorded extracellularly
      from On-Off DS ganglion cells in rabbit retina using everted eyecup preparations.
      Our data provide evidence that MLA-sensitive nAChRs are involved in mediating
      directionally selective responses to apparent motion and to a variety of complex,
      textured stimuli such as drifting square-wave gratings, transparent motion, and
      second-order motion.

PMID- 15733343
TI  - Retinal bipolar cells: contrast encoding for sinusoidal modulation and steps of
      luminance contrast.
AB  - Contrast encoding for sinusoidal modulations of luminance contrast was
      investigated by intracellular recording in the intact salamander retina. In what
      appears to be the first study of this kind for vertebrate bipolar cells,
      responses of the central receptive-field mechanism of cone-driven cells to
      modulation of 3 Hz were analyzed quantitatively via both signal averaging and a
      Fast Fourier Transform (FFT) while the retina was light adapted to 20 cd/m2.
      Depolarizing and hyperpolarizing bipolar cells showed very similar encoding. Both
      responded with sinusoidal waveforms whose amplitude varied linearly with
      modulation depths ranging up to 7-8%. The slope of the modulation/response curve
      was very steep in this range. Thus, the contrast gain was high, reaching values
      of 6-7, and the half-maximal response was achieved at modulations of 9% or less.
      At modulations above approximately 15%, the responses typically showed strong
      compressive nonlinearity and the waveform was increasingly distorted. At maximum
      modulation, the higher harmonics of the FFT constituted about 30% of the
      amplitude of the fundamental. Measurements were also made for cones and
      horizontal cells. Both cell types showed predominantly linear responses and low
      contrast gain, in marked contrast to bipolar cells. These results suggest that
      the high contrast gain and strong nonlinearity of bipolar cells largely arise
      postsynaptic to cone transmitter release. Further experiments were performed to
      compare responses to contrast steps versus those to sinusoidal modulation. In the
      linear range, we show that the contrast gains of cones and horizontal cells are
      low and virtually identical for both steps and sinusoidal modulations. In bipolar
      cells, on the other hand, the contrast gain is about two times greater for steps
      than that for the 3-Hz sine waves. These results suggest that mechanisms
      intrinsic to bipolar cells act like a high-pass filter with a short time constant
      to selectively emphasize contrast transients over slower changes in contrast.

PMID- 15733342
TI  - Probing inner retinal circuits in the rod pathway: a comparison of c-fos
      activation in mutant mice.
AB  - We have used wild-type mice and mice possessing defects in specific retinal
      circuits in order to more clearly define functional circuits of the inner retina.
      The retina of the nob mouse lacks communication between photoreceptors and
      depolarizing bipolar cells (DBCs). Thus, all light driven activity in the nob
      mouse is mediated via remaining hyperpolarizing bipolar cell (HBC) circuits.
      Transducin null (Tr alpha-/-) mice lack rod photoreceptor activity and thus
      remaining retinal circuits are solely generated via cone photoreceptor activity.
      Activation in inner retinal circuits in each of these mice was identified by
      monitoring light-induced expression of an immediate early gene, c-fos. The number
      of cells expressing c-fos in the inner retina was dependent upon stimulus
      intensity and was altered in a systematic fashion in mice with known retinal
      mutations. To determine whether c-fos is activated via circuits other than
      photoreceptors in the outer retina, we examined c-fos expression in tulp1-/- mice
      that lack photoreceptors in the outer retina; these mice showed virtually no c
      fos activity following light exposure. Double-labeling immunohistochemical
      studies were carried out to more clearly define the population of c-fos
      expressing amacrine cells. Our results indicate that c-fos may be used to map
      functional circuits in the retina.

PMID- 15733344
TI  - Effects of light intensity and pattern contrast on the ability of the land crab,
      Cardisoma guanhumi, to separate optic flow-field components.
AB  - Using a novel suite of computer-generated visual stimuli that mimicked components
      of optic flow, the visual responses of the tropical land crab, Cardisoma
      guanhumi, were investigated. We show that crabs are normally successful in
      distinguishing the rotational and translational components of the optic flow
      field, showing strong optokinetic responses to the former but not the latter.
      This ability was not dependent on the orientation of the crab, occurring both in
      "forwards-walking" and "sideways-walking" configurations. However, under
      conditions of low overall light intensity and/or low object/background contrast,
      the separation mechanism shows partial failure causing the crab to generate
      compensatory eye movements to translation, particularly in response to low
      frequency (low-velocity) stimuli. Using this discovery, we then tested the
      ability of crabs to separate rotational and translational components in a
      combined rotation/translation flow field under different conditions. We
      demonstrate that, while crabs can successfully separate such a combined flow
      field under normal circumstances, showing compensatory eye movements only to the
      rotational component, they are unable to make this separation under conditions of
      low overall light intensity and low object/background contrast. Here, the
      responses to both flow-field components show summation when they are in phase,
      but, surprisingly, there is little reduction in the amplitude of responses to
      rotation when the translational component is in antiphase. Our results
      demonstrate that the crab's visual system finds separation of flow-field
      components a harder task than detection of movement, since the former shows
      partial failure at light intensities and/or object/background contrasts at which
      movement of the world around the crab is still generating high-gain optokinetic
      responses.

PMID- 15733345
TI  - Local mechanisms for the separation of optic flow-field components in the land
      crab, Cardisoma guanhumi: a role for motion parallax?
AB  - Although a number of global mechanisms have been proposed over the years that
      explain how crabs might separate the rotational and translational components of
      their optic flow field, there has been no evidence to date that local mechanisms
      such as motion parallax are used in this separation. We describe here a study
      that takes advantage of a recently developed suite of computer-generated visual
      stimuli that creates a three-dimensional world surrounding the crab in which we
      can simulate translational and rotational optic flow. We show that, while motion
      parallax is not the only mechanism used in flow-field separation, it does play a
      role in the recognition of translational optic flow fields in that, under
      conditions of low overall light intensity and low contrast ratio when crabs find
      the distinction between rotation and translation harder, smaller eye movements
      occur in response to translation when motion parallax cues are present than when
      they are absent. Thus, motion parallax is one of many cues that crabs use to
      separate rotational and translational optic flow by showing compensatory eye
      movements to only the former.

PMID- 15733346
TI  - Postsynaptic calcium feedback between rods and rod bipolar cells in the mouse
      retina.
AB  - Light-evoked currents were recorded from rod bipolar cells in a dark-adapted
      mouse retinal slice preparation. Low-intensity light steps evoked a sustained
      inward current. Saturating light steps evoked an inward current with an initial
      peak that inactivated, with a time constant of about 60-70 ms, to a steady
      plateau level that was maintained for the duration of the step. The inactivation
      was strongest at hyperpolarized potentials, and absent at positive potentials.
      Inactivation was mediated by an increase in the intracellular calcium
      concentration, as it was abolished in cells dialyzed with 10 mM BAPTA, but was
      present in cells dialyzed with 1 mM EGTA. Moreover, responses to brief flashes of
      light were broader in the presence of intracellular BAPTA indicating that the
      calcium feedback actively shapes the time course of the light responses. Recovery
      from inactivation observed for paired-pulse stimuli occurred with a time constant
      of about 375 ms. Calcium feedback could act to increase the dynamic range of the
      bipolar cells, and to reduce variability in the amplitude and duration of the
      single-photon signal. This may be important for nonlinear processing at
      downstream sites of convergence from rod bipolar cells to AII amacrine cells. A
      model in which intracellular calcium rapidly binds to the light-gated channel and
      reduces the conductance can account for the results.

PMID- 15733347
TI  - The relationship between ambient lighting conditions, absolute dark-adapted
      thresholds, and rhodopsin in black and hypopigmented mice.
AB  - Significant variation in absolute dark-adapted thresholds is observed both within
      and between strains of mice with differing ocular pigmentation levels.
      Differences in threshold within a single strain are related to the Williams'
      photostasis effect, that is, photoreceptor rhodopsin levels are dependent upon
      ambient lighting conditions. To examine threshold differences among strains, we
      equalized rhodopsin levels by maintaining albino mice (c2J/c2J) at 2 x 10-4 cd/m2
      (dim light) and black mice at 2 x 102 cd/m2 (bright light). This resulted in
      ocular rhodopsin levels for albino mice (albino--dim) of 494 +/- 11 pmoles/eye
      and rhodopsin levels for black mice (black--bright) of 506 +/- 25 pmoles/eye. For
      comparison, rhodopsin levels in black mice maintained in dim light are 586 +/- 46
      pmoles/eye and 217 +/- 46 pmoles/eye in albino mice maintained in bright light.
      We found similar dark-adapted thresholds (6.38 log cd/m2 vs. 6.47 log cd/m2)) in
      albino and black mice with equivalent rhodopsin determined with a water maze
      test. This suggests that dark-adapted thresholds are directly related to
      rhodopsin levels regardless of the level of ocular melanin. The number of
      photoreceptors, photoreceptor layer thickness, and outer segment length did not
      differ significantly between albino (dark) and black mice (bright). These results
      demonstrate that the visual sensitivity defect found in hypopigmented animals is
      secondary to abnormal rhodopsin regulation and that hypopigmented animals have
      either an improper input to the photostasis mechanism or that the photostasis
      mechanism is defective.

PMID- 15733348
TI  - The effects of histamine on rat and monkey retinal ganglion cells.
AB  - Mammalian retinas receive input from the posterior hypothalamus, and the
      neurotransmitter in this pathway is histamine. To determine whether histamine
      influences ganglion cells, we analyzed the effects of histamine on their
      maintained and light-evoked activity in vitro. In monkeys, histamine increased
      the maintained firing rate in 42% of ganglion cells, decreased it in 38%, and had
      no effect in 20%. When histamine and the HR3 agonist, methylhistamine, were
      applied to the same cells in succession, their effects were sometimes different,
      a finding suggesting that at least one other histamine receptor is present. In
      addition, the responses of some ganglion cells to full-field light stimuli were
      decreased by histamine and methylhistamine. In rats, the effects of histamine
      were somewhat different. Histamine increased the maintained firing rate of 82% of
      ganglion cells. Methylhistamine and the HR2 agonist, dimaprit, had the same
      effects as histamine. In some cells, histamine increased the light responses, but
      in others it decreased them. Histamine had no effect on ganglion cells in either
      species when synaptic transmission was blocked by low Ca2(+)/high Mg2+ Ames
      medium. Thus, the major effects of histamine were on the maintained activity of
      retinal ganglion cells. In both rats and monkeys, 80% or more of the ganglion
      cells were affected by histamine, and these responses were mediated by at least
      two of the histamine receptor subtypes.

PMID- 15733349
TI  - Visual pigment composition in zebrafish: Evidence for a rhodopsin-porphyropsin
      interchange system.
AB  - Numerous reports have concluded that zebrafish (Danio rerio) possesses A1-based
      visual pigments in their rod and cone photoreceptors. In the present study, we
      investigated the possibility that zebrafish have a paired visual pigment system.
      We measured the spectral absorption characteristics of photoreceptors from
      zebrafish maintained in different temperature regimes and those treated with
      exogenous thyroid hormone using CCD-based microspectrophotometry. Rods from fish
      housed at 15 degrees C and 28 degrees C were not significantly different, having
      lambda max values of 503 +/- 5 nm (n = 106) and 504 +/- 6 nm (n = 88),
      respectively. Thyroid hormone treatment (held at 28 degrees C), however,
      significantly shifted the lambda max of rods from 503 +/- 5 nm (n = 194) to 527
      +/- 8 nm (n = 212). Cone photoreceptors in fish housed at 28 degrees C (without
      thyroid hormone treatment) had lambda max values of 361 +/- 3 nm (n = 2) for
      ultraviolet-, 411 +/- 5 nm (n = 18) for short-, 482 +/- 6 nm (n = 9) for medium-,
      and 565 +/- 10 nm (n = 14) for long-wavelength sensitive cones. Thyroid hormone
      treatment of fish held at 28 degrees C significantly shifted the lambda max of
      long-wavelength sensitive cones to 613 +/- 11 nm (n = 20), substantially beyond
      that of the lambda max of the longest possible A1-based visual pigment
      (approximately 580 nm). Thyroid hormone treatment produced smaller shifts of
      lambda max in other cone types and increased the half-band width. All shifts in
      photoreceptor lambda max values resulting from thyroid hormone treatment matched
      predictions for an A1- to A2-based visual pigment system. We therefore conclude
      that zebrafish possess a rhodopsin-porphyropsin interchange system that functions
      to spectrally tune rod and cone photoreceptors. We believe that these
      observations should be carefully considered during analysis of zebrafish spectral
      sensitivity.

PMID- 15733351
TI  - [Existing problems in current pediatric medical research in China].

PMID- 15733353
TI  - [Pay close attention to and strengthen studies on medical issues related to
      girlschild].

PMID- 15733352
TI  - [Hemofiltration cure black carp's bile poisoning: one case report].

PMID- 15733354
TI  - [Prevalence of iron deficiency in children aged 7 months to 7 years in China].
AB  - OBJECTIVE: To collect epidemiological data of iron deficiency in Chinese children
      7 months to 7 years of age, so more rational strategies of prevention and
      treatment against iron deficiency can be made. METHODS: All the 31 provinces,
      municipalities and autonomous regions in China were first divided into 3 major
      regions based on geographic location socioeconomic developmental status. Among
      them, 15 provinces, municipalities and autonomous regions were randomly selected:
      6 from the coastal regions, 5 from inland regions and 4 from remote regions.
      Then, 26 cities/counties were further selected from the 15 provinces,
      municipalities and autonomous regions. Ultimately, 9118 children aged 7 months to
      7 years were selected as study subjects. Hemoglobin (Hb) was measured by
      cyanmethemoglobin assay, zinc protoporphorin by hemofluorescence assay and serum
      ferritin by radioimmunoassay. RESULTS: The prevalence rates of iron depletion
      (ID) and iron deficiency anemia (IDA) were 32.5% and 7.8% respectively in
      children 7 months to 7 years in China. The prevalence rates were highest in
      infants (ID 44.7%, IDA 20.8%), followed by toddlers aged 1 - 3 years (ID 35.9%,
      IDA 7.8%) and preschoolers aged 4 to 7 years (ID 26.5%, IDA 3.5%), with
      statistically significant differences (P < 0.01). In countryside, the prevalence
      rates of ID were 35.8%, 31.0% and 27.6%, and the prevalence rates of IDA were
      30.1%, 15.5% and 6.3% for children 7 to 12 months, 1 to 3 years and 4 to 7 years
      of age, respectively. While Hb measurements averaged (98.8 +/- 9.1) g/L, (98.2 +/
      10.5) g/L and (101.2 +/- 8.6) g/L respectively for the same age groups with IDA.
      In cities, the corresponding figures were 48.1%, 38.0% and 26.0% for ID, 16.8%,
      4.4% and 1.9% for IDA, (101.0 +/- 6.8) g/L, (102.8 +/- 6.9) g/L and (104.2 +/-
      4.4) g/L for average Hb measurements. There were statistically significant
      difference between the overall prevalence rate of iron deficiency in children
      living in rural areas and that of children in cities (42.0% versus 39.5%, P <
      0.01). Obviously, there were significantly more urban children aged 6 months to 3
      years suffering from latent iron deficiency than their rural counterparts, while
      there were more rural children with iron deficiency anemia. The average Hb
      measurements from each rural children age group with IDA were lower than that of
      their urban peers (P < 0.01). CONCLUSIONS: ID was more prevalent than IDA in each
      age group in children, suggesting that latent iron deficiency was currently one
      of the major nutritional problems for Chinese children. The present study also
      showed that infants were still at higher risk for iron deficiency in spite of
      rapid socioeconomic development in the last two decades. Urban children were more
      likely to be inflicted by latent iron deficiency, while rural children were more
      prone to development of iron deficiency anemia. The susceptibility of rural
      children to development of iron deficiency anemia may be related to lower
      socioeconomic status of their families, poor hygienic conditions etc.

PMID- 15733355
TI  - [A case of congenital mesenchymal hamartoma in oral cavity].

PMID- 15733356
TI  - [Parental education to reduce blood lead levels in children with mild and
      moderate lead poisoning: a randomized controlled study].
AB  - OBJECTIVE: To evaluate the effectiveness of parental education on reducing lead
      exposure of children by examining the changes in blood lead levels of children
      whose parents receiving or not receiving educational intervention. METHODS: Two
      hundred children with confirmed blood lead levels beyond 100 microg/L were
      selected. They were randomized into two groups, 107 children in study group and
      93 in control. At the beginning of the study, parents of both study and control
      groups were called for interview to complete KABP questionnaire and lead study
      questionnaire. The study group was provided with interventional measures while
      control group was not contacted until the end of study. Intervention of parental
      education was undertaken by means of a TV program, a set of slides and a
      brochure, and focused on the questions regarding harmful effects of lead
      poisoning, the sources of environmental lead and prevention of this preventable
      disease. Tests for blood lead level were repeated for both study and control
      groups 3 months after the determination of the initial blood lead level. RESULTS:
      All the relevant knowledge of health effect, lead sources and prevention of
      childhood lead poisoning of participating parents of study group were improved
      significantly (chi(2) = 14.06, 13.07, 10.08, 28.26, P < 0.01) after educational
      intervention while parents control group also were significantly improved in the
      sub-catalogs of concept and prevention (chi(2) = 7.69, 8.64, P < 0.01), but not
      the health effect and sources of childhood lead poisoning. Children and parents'
      behavior in study group was improved accordingly and significantly. Less children
      ate popcorn (chi(2) = 4.08, P < 0.05), less children drank tap-water in the
      morning (chi(2) = 23.04, P < 0.01), more kids washed their hands before eating
      (chi(2) = 5.82, P < 0.05), less kids played on road side (chi(2) = 9.60, P <
      0.01), and more parents changed their coat or took shower or washed hands before
      going home after work (chi(2) = 4.00, P < 0.05). But in the control group only
      the number of kids playing on road side was decreased significantly (chi(2) =
      9.60, P < 0.01). A general decline in blood lead levels was detected in both
      groups with statistical significance at P < 0.01. However, the decrease in blood
      lead levels was more remarkable in the study group. There was average reduction
      of 55 microg/L (35%) in blood lead levels for study group (t = 4.979, P < 0.01)
      and an almost 33 microg/L (20%) for control (t = 3.398, P < 0.01). The reduction
      in blood lead level was 22 microg/L greater in study group (t = 3.531, P < 0.01).
      The study also showed that the effectiveness of the educational interventions
      depended upon various aspects. Fourteen variables were included in the stepwise
      multiple regression equation of blood lead level changes. Such as parents'
      occupational exposure to lead, the improvement of knowledge about prevention of
      childhood lead poisoning, the chang of habit of snacks intake, parents' education
      levels, the change of attitude of parents for the childhood lead poisoning, etc.
      CONCLUSION: Educating parents is proved to be an effective approach for children
      with mild and moderate lead poisoning.

PMID- 15733357
TI  - [Reproductive expectation and gender preferences of parents in poverty areas of
      China].
AB  - OBJECTIVE: The reproductive goals of married couples living in impoverished areas
      of China affect survival rates and quality of life of female children in those
      areas. The goal of this study was to collect information on parents' attitudes
      toward reproduction, gender preferences/prejudices, and to collect relevant
      socioeconomic and demographic data. METHODS: Random sample families were enrolled
      from 3 poverty counties. Sample size included parents of 1800 children from birth
      to 6 years old. The children were divided into 6 age groups at one-year interval.
      Baseline data were collected and a questionnaire (endorsed by UNICEF) was used to
      evaluate reproductive expectations and gender preferences of parents. RESULTS:
      (1) The success of the One Child Family program has lead to a decreased overall
      birthrate. (2) The gender ratio (boys:girls) of the 3 counties studied was 100:87
      100:95-100:97. No gender imbalance was found in this study. (3) The "Boy
      Preference" was still expressed by both fathers (69.0%) and mothers (65.7%).
      Approximately 40% of fathers and 37% of mothers interviewed expressed that only a
      male child would be acceptable. (4) Approximately 65% of both fathers and mothers
      recognize that girls are more likely to care for aging parents. CONCLUSION:
      Government initiatives have encouraged small families, yet in this region gender
      ratio of newborns is still normal. More educational and social programs are
      needed to influence perceptions regarding gender and to eliminate the suboptimal
      status/poorly perceived value of girls in many societies.

PMID- 15733358
TI  - [Longitudinal study on the age at childhood onset in children from Shanghai and
      its effects on child growth].
AB  - OBJECTIVE: The infancy-childhood-puberty (ICP) growth model divides human growth
      into three additive and partly superimposed phases: infancy, childhood, and
      puberty reflecting the endocrinology of the growth process. The childhood phase
      of the ICP model has been assumed to start during the second half-year of life
      and slowly decelerates, although it continues into puberty until growth ceases.
      This phase has been taken to mirror the effect of growth hormone (GH). The age at
      onset of the phase of growth, normally occurring between 6 and 12 months of age
      is recognized to be an important time event at postnatal human growth. The aims
      of this study were to study the age at childhood onset in Shanghai children and
      its effect on child growth, and to compare these results with the results
      obtained from Swedish longitudinal studies. METHODS: The study population
      consisted of 1 720 children born between January 1, 1980, and December 31, 1990
      in Fenglin Community, Shanghai, who got a continual monitoring at the clinic from
      birth to six years of age. The age at onset of the 'childhood phase' of growth
      was determined individually, in units of one month, by visual inspection of the
      data contained within the individual, computer-generated, ICP-based growth chart
      for both length and length velocity. T tests, chi(2) tests and multiple linear
      regression analyses were used in data analysis. RESULTS: There was a significant
      (P < 0.05) difference in the distribution of the age at onset of the childhood
      phase of growth between Shanghai and Swedish populations. The mean age of the
      infants at onset of the 'childhood phase' of growth was 11.2 months in boys and
      10.7 months in girls. Compared to their Swedish counterparts, these means
      occurred 1.3 months later in boys and 1.4 months later in girls. Both age at
      onset of the 'childhood phase' of growth and length at six months of age
      significantly (P < 0.05) contributed to the attained height from 12 months of age
      onward; one month delay in the onset of the 'childhood phase' of growth reduced
      height, at 5 years of age, by 0.4 cm in boys and 0.56 cm in girls. The mean
      values of length/height among the four groups of the age of the childhood onset,
      i.e. 6 m-, 9 m-, 12 m-, >/= 15 m, were found to be significantly (P < 0.05)
      different from 12 month of age onward. However, a significant (P < 0.05)
      difference in the mean length/height velocities among the four groups was in
      principle only found during the following intervals: 3 - 6, 6 - 9, 9 - 12, and 12
      - 18 months of age. The mean values of BMI among the four groups of the age of
      the childhood onset showed significantly (P < 0.05) different only in 9 and 12
      months of age. The mean values of BMI velocity among the four groups of the age
      of the childhood onset were found to be significantly (P < 0.05) different in
      four age intervals: 3 - 6, 6 - 9, 9 - 12, and 12 - 18 months of age. The age at
      onset of the 'childhood phase' of growth was negatively associated (P < 0.05)
      with mid-parental height, though positively related (P < 0.05) to height at six
      months of age. A simple linear regression was applied to the age at onset of the
      'childhood phase' of growth and mid-parental height. It was found that the age at
      onset of the childhood phase' of growth was 1.5 months later in boys and 1.3
      months later in girls, for children with a mid-parent height being -2SD below the
      mean in comparison to the children of tall parents, i.e. a mid-parental height
      equals to mean +2SD. CONCLUSIONS: The age at childhood onset is equally important
      when studying children from Shanghai, as it is with their Swedish counterparts.

PMID- 15733360
TI  - [A case of infant acute myeloid leukemia (M2b) which developed initially facial
      nerve palsy].

PMID- 15733359
TI  - [Individual and family factors influencing vocabulary development in toddlers].
AB  - OBJECTIVE: Many researchers have conducted studies on child language development
      and relevant risk factors, but most of these studies were about English-speaking
      children and few of them were on Chinese-speaking children, and less reports of
      studies on language development of infants or toddlers are available as compared
      to those on children above 3 years of age. The objective of this study was to
      assess the level of vocabulary development of healthy toddlers in urban Beijing
      and to investigate toddlers' physical and psychological development and
      socioeconomic status of toddlers' family so as to identify factors related to
      toddlers' language development and provide basis for instructing parents child
      rearing. METHOD: This is a quantitative cross-sectional study. Using Chinese
      Communicative Development Inventory mandarin version, (CCDI) and related
      background questionnaire, a survey was conducted among the parents or care givers
      of 1056 healthy toddlers (16 approximately 30 months), randomly stratified and
      selected from two areas of four urban districts in Beijing. The children who were
      born prematurely, who had low birth weight, or who were deaf, dumb or with
      disability, were excluded from this study. The mothers who were deaf, dumb or
      having disability were not included in this study, either. Rank sum test was used
      to compare the vocabulary scores between boys and girls at the same age. Single
      and multiple factors analysis were used to find related factors. RESULTS: By 16
      months of age, boys could speak about 22 words and girls 84 words on the CCDI. By
      29 - 30 months of age, boys could speak about 725 words and girls 752 words on
      the CCDI. The level of vocabulary development of healthy toddlers in urban
      Beijing was higher than that reported in previous studies of English-speaking
      children. Girls had higher vocabulary scores than boys in a few different age
      groups. Single factor analysis showed that the ages of father and mother, income
      of father, the language used by care-givers and GDP of the families were factors
      related to families of toddlers and the age, gender, height, weight and the age
      at which the toddlers began to speak were factors related to individuals.
      Multiple factors analysis showed that higher education level of mothers, younger
      father, earlier beginning of children to speak, toddlers' amiable disposition and
      emotion, girls, toddlers' age and height positively correlated with toddlers'
      vocabulary score. CONCLUSION: The level of vocabulary development of healthy
      toddlers in urban Beijing is on the high side. Certain individual and familial
      factors may influence toddlers' language development. It is suggested that health
      workers should pay attention to the toddlers' language development. The toddlers'
      parents and caregivers should be taught how to interact with and talk to their
      children and how to promote children to develop healthy disposition and emotion.

PMID- 15733361
TI  - [Prospective study on prognosis of infants with neonatal subependymal cysts].
AB  - OBJECTIVES: It is confirmed that most neonatal subependymal cysts (SEC) are
      closely correlated with intrauterine infection and the short-term prognosis of
      SEC is not very good. Little information about the long-term prognosis of SEC is
      available. The purpose of the present study was to explore the short-term and
      long-term prognosis of neonatal SEC cases via a 6-year follow up. METHODS:
      Seventy SEC neonates detected by cranial ultrasound between October 1993 and
      October 1994 were enrolled into SEC group and 70 healthy neonates into control
      group. Serum antibodies (IgG and IgM) to cytomegalovirus (CMV), toxoplasma and
      rubella virus and PCR for these pathogens (except for rubella virus) were
      measured in the two groups. CMV-PCR was also performed for urine specimens.
      Cranial sonography assessment, physical growth evaluation, Bayley developmental
      scale or Wyeth developmental scale, brain-stem auditory evoked potential (BAEP)
      and vision examination were undertaken at 3, 6, 12 months and 6 years in the two
      groups. RESULTS: The positive rate of CMV-IgM and blood CMV-PCR in SEC group was
      significantly higher than those of control group (19.1% vs. 5.7%, 12.9% vs.
      2.9%). The positive rate of urine CMV-PCR in SEC group was also significantly
      higher (40% vs 17.1%). No significant difference could be found in the positive
      rate of PCR for toxoplasma and rubella-IgM between the two groups. The weight and
      height of infants with SEC were obviously lower than those in control group
      during the first year after birth. The parameters of the physical development in
      SEC infants reached the similar level as controls till 6 years old. However, the
      index of mental development below 80 was more often seen in infants with SEC
      comparing to that in control group during the whole six years. There were no
      abnormal findings either in BAEP or vision examination in the two groups.
      CONCLUSION: Infants with SEC may show a transient retardation of physical growth
      after birth, while their mental developmental retardation might last for longer
      time. It is suggested that cranial ultrasound examination should be performed in
      all neonates for the detection of SEC, and a longer follow-up should be done for
      infants with SEC.

PMID- 15733362
TI  - [Obese children with benign acanthosis nigricans and insulin resistance: analysis
      of 19 cases].
AB  - OBJECTIVE: The prevalence of obesity and of type 2 diabetes mellitus in children
      have increased in the Chinese population over the past two decades, and thus
      diabetes prevention has become a major concern of public health agencies.
      Identification of individuals at risk for diabetes is an essential first step in
      designing and implementing intervention programs. Insulin resistance is the
      hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with
      hyperinsulinemia and impaired glucose tolerance are well accepted as being at
      high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable
      marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has
      not been systematically evaluated in obese children. In order to further explore
      the relationship between obese childhood with benign acanthosis nigricans and
      insulin resistance and type 2 diabetes mellitus, we examined 19 obese children
      with benign acanthosis nigricans. METHODS: Nineteen of seventy six obese children
      (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University
      School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin
      biopsies were performed in these 19 obese children with acanthosis nigricans for
      final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were
      measured on fasting blood specimens and anthropometric parameters including
      waist/hip ratio, fat mass, body fat percentage and body mass index were examined.
      Oral glucose tolerance tests were also performed in these 19 children with benign
      acanthosis nigricans. RESULTS: Anthropometric parameters including waist/hip
      ratio, fat mass, body fat percentage and body mass index as well as fasting
      insulin level in acanthosis nigricans group were significantly higher than that
      of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these
      19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating
      apparent insulin resistance. One of them was diagnosed as type 2 diabetes
      mellitus and ten of them showed impaired oral glucose tolerance. CONCLUSION:
      Childhood benign acanthosis nigricans is tightly associated with obesity,
      hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be
      used as a reliable index of insulin resistance.

PMID- 15733363
TI  - [Study on mesenchymal stem cells entering the brain through the blood-brain
      barrier].
AB  - OBJECTIVE: Neonatal hypoxic-ischemic encephalopathy (HIE) harms the lives and
      health of newborn infants and children severely. The prognosis is not satisfied,
      especially of the severe HIE. Mesenchymal stem cells (MSCs) can secrete a series
      of growth factors and neurotrophic factors. As well they have the potential
      ability to differentiate to the neural cells in vitro and in vivo. Therefore MSCs
      transplantation has been employed as a source of progenitor cells for cell
      therapy in patients with HIE in order to promote recovery of brain function and
      reduce the sequelae. Studies have shown that MSCs could enter the cerebral
      parenchyma and differentiate to neural cells through systemic infusion, but most
      of the researches applied adult stroke animal models. This study used neonatal
      HIE models to test the hypothesis that MSCs could enter the brain of newborn
      Wistar rats through the blood-brain barrier (BBB) by intraperitoneal infusion
      followed by observing the characteristics of the distribution and differentiation
      of MSCs in brain tissues, and exploring the effects of hypoxic-ischemic brain
      damage to the penetration and differentiation of MSCs. METHODS: Isolation and
      purification of MSCs were established from the whole bone marrow of juvenile
      Wistar rats by removing the nonadherent cells in primary and passage cultures.
      For cellular identification, MSCs of three to five passages were continuously pre
      labeled with 5-bromo-2-deoxyuridine (BrdU) for 72 hours before transplantation.
      Animal models of HIE were built in 7-day-postnatal Wistar rats according to the
      method described by Rice. Two hours after hypoxia-ischemia, rats in HIE group (n
      = 8) were intraperitoneally infused with MSCs (4 x 10(6), 0.5 ml). In control
      group (n = 8), 7-day-postnatal normal Wistar rats were intraperitoneally infused
      with the same amount of MSCs. All rats were sacrificed and their cerebra were
      sectioned by cryomicrotome 14 days after transplantation. Immunohistochemical
      staining with chromogen diaminobenzidine (DAB) was used to detect and measure the
      cells derived from MSCs, and study the characteristics of distribution. To
      determine the differentiation of the BrdU positive cells entering the brains,
      immunofluorescence double labeling for BrdU and neural cells specific antigens
      was performed. RESULTS: MSCs were distributed throughout the cerebra in both
      groups at the 14th day after transplantation. The number of MSCs detected was
      2415 +/- 226 in the control group, and 3626 +/- 461 in HIE group, respectively (t
      = 6.68, P < 0.05). More BrdU reactive cells were observed in the right ischemic
      hemisphere (1904 +/- 267) than in the contralateral hemisphere (1723 +/- 204), (t
      = 4.47, P < 0.05). No significant difference was found while comparing both
      cerebral hemispheres of the control group (t = 0.31, P > 0.05). In the HIE group,
      MSCs distributed more extensively, and some focal aggregations of MSCs were
      noticed. A few MSCs expressed Nestin-protein marker of neural progenitor cells,
      and almost none of the MSCs which expressed proteins characteristic of neuron
      (e.g. NSE) and astrocyte (e.g. GFAP) was detected at the 14th day after
      transplantation. CONCLUSION: 1. MSCs could enter the cerebral parenchyma through
      BBB and migrate throughout the brain by intraperitoneal infusion. 2. More MSCs
      injected intraperitoneally were localized and directed to the sites of hypoxic
      ischemic brain damage. 3. Transplanted MSCs could not differentiate to neuron and
      astrocyte without other interventions during 14 days after transplantation.

PMID- 15733364
TI  - [Treatment of advanced malignant solid tumors in children with autologous
      hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To investigate the efficacy of autologous hematopoietic stem cell
      transplantatation in children with advanced solid tumors. METHODS: Bone marrow
      was collected from the anterior crista of iliac in both sides in 13 cases while
      peripheral mononuclear cell was harvested with CS-3000 cell separator in other 15
      patients after G-CSF mobilization. Since one of them was suspected to have bone
      marrow involvement of the neuroblastoma cells, the autograft was purged with
      CliniMACS based on the CD34 positive selection. Conditioning regimen was CBV
      protocol (cyclophosphamide + bischloro-nitrosourea, i.e., BCNU + etopside) in two
      children with Hodgkin's disease and etopside plus carboplatin plus melphalan in
      others. RESULTS: The number of mononuclear cells collected from bone marrow or
      peripheral blood was equal to (5.4 +/- 2.1) x 10(8)/kg and (4.1 +/- 1.9) x
      10(8)/kg, respectively. Hematopoietic reconstitution was achieved in all
      patients. Mean time of the neutrophil count recovery to 0.5 x 10(9)/L and mean
      time of platelet recovery over 2.0 x 10(9)/L were 11.8 +/- 5.7 and 21.0 +/- 9.3
      days, respectively. Three units of packed red blood cells and three units of
      platelet products were transfused in the course of transplantation on average. A
      total of 12 children developed neutropenic fever and 3 of them had positive blood
      culture, including staphylococcus epidermal, staphylococcus saprophyte and
      bacillus subtilis. None of the children died of transplantation-associated
      complication. One child developed acute renal failure, pulmonary edema and
      pericardial effusion followed by respiratory distress syndrome. Mechanical
      ventilation and pulmonary surfactant were used and the patient recovered at last.
      Another patient developed BCNU associated pulmonary injury, severe pulmonary
      hypertension and eosinophilosis and recovered after treatment. The mean follow up
      time was 13 months. Among the 27 children, five died of relapse 5 months after
      transplantation, and one case of NHL had CNS involvement 3 months after
      transplantation but has got 17 months of survival till now. The remaining twenty
      one children were in status of disease-free survival. CONCLUSION: Autologous stem
      cell transplantation might be effective in the treatment advanced solid tumors in
      children.

PMID- 15733365
TI  - [Relationship between the expression of murine double minute 2 oncogene and non
      Hodgkin lymphoma in childhood].
AB  - OBJECTIVE: To investigate the relationship between the expression of murine
      double minute 2 (MDM2) oncogene and non-Hodgkin lymphoma (NHL) in childhood.
      METHODS: Thirty-one cases of NHL were enrolled in this study as patient group and
      8 cases of lymphadenitis as control group. (1) Immunohistochemistry
      ultrasensitive S-P assay was used to detect the expression of MDM2 protein in
      pathological tissues in all cases. Positive cells were dyed yellow or brown in
      nuclei. MDM2 positive cell was defined as >/= 10% of the tumor cells were
      positive, which was overexpression of MDM2 protein. (2) RT-PCR (reverse
      transcription-polymerase chain reaction) was performed to value the
      overexpression of MDM2 mRNA in the pathological tissues and mononuclear cells in
      peripheral blood. While the ratio of MDM2/beta-actin was >16% was defined as
      overexpression of MDM2 mRNA. RESULTS: (1) Rates of overexpression of MDM2 protein
      and MDM2 mRNA were 64.5% and 61.3%, respectively, which were significantly
      different as compared to that of control group (P < 0.05 and P < 0.01,
      respectively). (2) The relationship analysis among subgroups in the experiment
      group showed that the overexpression of MDM2 protein did not correlate with
      classifications of working formulation, cellular origin, sex, clinical stage and
      involved extranodal sites (P > 0.05), but significantly correlated with
      classifications of B status and the increased serum LDH level (P < 0.05). It was
      shown that the overexpression of MDM2 mRNA did not correlate with classifications
      of working formulation, cellular origin, sex and clinical stage (P > 0.05),
      significantly correlated with B status (P < 0.05), and was remarkably
      significantly correlated with the involved extranodal sites and the increased
      serum LDH level (P < 0.01). (3) It was demonstrated that the overexpression of
      MDM2 mRNA in the pathological tissues was similar to the overexpression of MDM2
      protein in the pathological tissues and MDM2 mRNA in peripheral blood (P > 0.05,
      kappa = 0.655 and 0.571), and the overexpression of MDM2 protein in the
      pathological tissues was similar to that of MDM2 mRNA in peripheral blood (P >
      0.05, kappa = 0.609). CONCLUSIONS: (1) The rate of MDM2 oncogene overexpression
      was quite high. (2) The overexpression of MDM2 protein in pathological tissues
      determined by using immunohistochemistry ultrasensitive S-P assay was similar to
      that of MDM2 mRNA in pathological tissues detected by using RT-PCR method. Both
      methods might be used to detect the overexpression of MDM2 oncogene in the cases
      of childhood NHL. (3) The overexpression of MDM2 oncogene related to the poor
      status and poor prognosis of patients with childhood NHL.

PMID- 15733366
TI  - [Inoculation of bacille calmette guerin combined with intraperitoneal adenosine
      injection enhances antibacterial effect of macrophage against Mycobacterium
      tuberculosis in mice].
AB  - OBJECTIVE: The protection rate of inoculation with BCG vaccine is only 50
      percent, and most of patients with tuberculosis had a history of BCG vaccine
      inoculation. Adenosine (ADO) has an immunomodulating effect; it promotes immune
      reaction by increasing number of macrophage and enhancing phagocytosis. The
      present study was designed to investigate if combined use of adenosine with BCG
      enhances the anti-Mycobacterium tuberculosis effect of macrophage in mice.
      METHODS: Fifty BALB/C mice were divided randomly into 3 groups: BCG group (n =
      21), BCG plus ADO group (n = 21) and control group (n = 8). The mice in BCG and
      BCG plus ADO groups were inoculated with 0.1 ml BCG intradermally and the mice in
      BCG plus ADO group were injected intraperitoneally with ADO 30 mg/(kg.d) for 5
      days. The mice in BCG group and control group were injected with NS 0.1 ml/d for
      5 days. Six weeks after the last injection, all mice were challenged with
      intravenous 1 x 10(6) CFU human Mycobacterium tuberculosis virulent strain. After
      challenging, lung and spleen specimens were taken at the 10th, 20th and 30th days
      from the mice of BCG and BCG plus ADO groups and at the 30th day from mice in
      control group. The pathological examinations of lung and spleen sections were
      performed after HE staining and acid-fast staining, and detection of cell
      apoptosis was also performed. RESULTS: Consolidation with neutrophil infiltration
      was found in most of the lung tissue taken at the day 30; there were a lot of
      tuberculous granulomas and Mycobacterium tuberculosis in the lungs of control
      group. The alveolar septum in BCG gradually became wide and in interstitium
      lymphocyte infiltration dominated, and there were less tuberculous granulomas but
      there were large number of Mycobacterium tuberculosis in the lungs from 10th to
      30th days after challenging. The widening of alveolar septum and consolidation of
      lung tissue in BCG plus ADO group became milder with monocytes infiltration, and
      there were few tuberculosis granulomas and Mycobacterium tuberculosis in the
      lungs from 10th to 30th days after challenging. CONCLUSION: ADO could increase
      the number of monocyte-macrophages and promoted anti-bacterial effects of these
      cells.

PMID- 15733367
TI  - [Death of a case caused by anaphylaxis to azithromycin].

PMID- 15733369
TI  - [Diagnosis and treatment of hypoxic-ischemic encephalopathy in premature
      infants].

PMID- 15733368
TI  - [Macrolide-resistant Streptococcus pneumoniae in the pediatric population in
      Beijing].
AB  - OBJECTIVE: To analyze the mechanisms of macrolide resistance in Streptococcus
      pneumoniae from children in Beijing. METHODS: The MICs of penicillin and
      erythromycin were determined by the E-test methods for 200 Streptococcus
      pneumoniae isolates collected from 2002 to 2003 at Beijing Children's Hospital.
      MICs of azithrhomycin, clarithromycin, acetylspiramycin and clindamycin for 147
      erythromycin-resistant isolates were detected by the agar dilution methods. For
      phenotyping, macrolide resistance induction tests were used in erythromycin
      resistant isolates. PCR was used to determine the presence of the erythromycin
      resistant genes. RESULTS: Of 200 Streptococcus pneumoniae isolates, 89.5% were
      resistant to erythromycin. In 147 erythromycin-resistant isolates, resistance
      rates were as follows: azithromycin, 100%; clarithromycin, 100%;
      acetylspiramycin, 95.2%; and clindamycin, 95.9%. The most common macrolide
      resistance phenotype was the cMIS phenotype (95.9%), 1.4% had the iMLS phenotype
      and 2.7% the M phenotype. Erythromycin-resistant isolates were characterized for
      the underlying resistance genotype, with 79.6% having the ermB genotypes, 17.7%
      having both ermB and mefA, 2.7% having the mefA, and none having neither ermB nor
      mefA genotypes. CONCLUSIONS: The rates of carriage of macrolide-resistant
      Streptococcus pneumoniae by children were high in Beijing during 2002 - 2003.
      cMLS was the most prevalent phenotype among erythromycin-resistant Streptococcus
      pneumoniae isolates, and ribosomal modification (ermB gene coded) was the main
      resistance mechanism against macrolides in Beijing region.

PMID- 15733370
TI  - [A case of childhood chronic lymphocytic leukemia].

PMID- 15733371
TI  - [Children are the future of the world-a brief introduction to the 23rd World
      Congress of Pediatrics].

PMID- 15733372
TI  - [A case of neonatal Sturge-Weber syndrome].

PMID- 15733373
TI  - [Effects of obesity induced by high fat diet on renin-angiotensin-aldosterone
      system related to cardiac structure and function of rats].

PMID- 15733374
TI  - [The expression and significance of peroxisome proliferator-activated receptor
      gamma in airway remodeling of asthmatic rats].

PMID- 15733375
TI  - [Detection of serum cytokines and its clinical significance in children with
      acute idiopathic thrombocytopenic purpura].

PMID- 15733376
TI  - [Continuous hemofiltration in the treatment of children's acute renal failure].

PMID- 15733377
TI  - [Cytomegalovirus infection following cord blood transplantation for children].

PMID- 15733378
TI  - [Four cases of meconium peritonitis in infants].

PMID- 15733379
TI  - [Detection of virulence genes of Escherichia coli from newborn infants].

PMID- 15733380
TI  - [Clinical significance of rapid blood culture in diagnosis of neonatal
      septicemia].

PMID- 15733381
TI  - [Ring chromosome 14 syndrome: a case report].

PMID- 15733382
TI  - [Craniocerebral tumor-caused hypothalamus syndromes in a case].

PMID- 15733383
TI  - [Congenital generalized lipodystrophy: report of a case].

PMID- 15733384
TI  - [Carcinogenic effects of sterigmatocystin and deoxynivalenol in NIH mice].
AB  - OBJECTIVE: To further explore the carcinogenic activity of Sterigmatocystin (ST)
      and the possible synergistic carcinogenic effect of deoxynivalenol (DON) in NIH
      mice. METHODS: NIH mice were randomly divided into 6 groups, 30 in each. Five
      groups of mice were given by gastric intubation ST 3 microg/kg, ST 30 microg/kg,
      ST 3 microg/kg + DON 1.5 microg/kg, ST 30 microg/kg + DON 1.5 microg/kg and DON
      1.5 microg/kg respectively, 3 times a week for 24 weeks. The remaining group of
      mice was given normal saline accordingly, serving as control. All mice were fed
      with HPLC-confirmed mycotoxin-free food, analysis. The mice were killed and
      pathologically examined at 58th and 74th weeks. RESULTS: No pathological changes
      were found in the control group of mice. Adenocarcinoma of lung was observed in
      25.0%, 41.7%, 62.5%, 69.2% and 37.5% of mice given ST 3 microg/kg, ST 30
      microg/kg, ST 3 microg/kg + DON 1.5 microg/kg, ST 30 microg/kg + DON 1.5
      microg/kg and DON 1.5 microg/kg, respectively. In addition, dysplasia of
      glandular stomach was detected in 50.0%, 58.3%, 37.5%, 53.8% and 25.0% of mice
      similarly treated. CONCLUSION: Oral administration of ST or DON can induce
      adenocarcinoma in lung and dysplasia of glandular stomach in NIH mice. There is
      synergistic carcinogenic effect when both ST and DON are given.

PMID- 15733385
TI  - [In vitro induction of immune response by dendritic cells pulsed with TRAG-3
      derived cytotoxic T lymphocyte epitope].
AB  - OBJECTIVE: To explore the in vitro immune response to taxol resistance associated
      antigen 3 (TRAG-3)-derived cytotoxic T lymphocyte (CTL) epitope-pulsed dendritic
      cell (DC). METHODS: The HLA-A2.1 restricted CTL epitope of TRAG-3 was previously
      identified to be a nonameric peptide sequence from 58 to 66 amino acid residues
      (TRAG-3(58-66)). The peptide was synthesized according to Fmos procedure,
      purified and molecular weight determined. Peripheral blood mononuclear cells
      (PBMC) of normal HLA-A2.1(+) individuals were used to isolate DC and DCs'
      phenotype identified by flow cytometry. Induction of CTL was achieved by in vitro
      stimulation of HLA-A2.1(+) PBMC with peptide-pulsed DC. CTL activity against HLA
      A2.1(+)/TRAG-3(+) melanoma cell line LB373-MEL was assessed by (51)Cr release
      assay and IFN-gamma released by ELISA. RESULTS: The synthetic nonameric peptide
      was above 90% pure and the determined values of molecular weight were conformed
      to their theoretical values. The phenotype of the isolate DCs was characteristic
      for mature ones. PBMC stimulated in vitro by TRAG-3-derived epitope-pulsed DCs
      for three times could specifically kill the target cells and secreted high
      concentration of IFN-gamma. CONCLUSION: TRAG-3-derived epitope-pulsed DC can
      elicit specific anti-tumor immune response in vitro. Clinical trials using it as
      tumor vaccine may be feasible as specific immunotherapy for patients with TRAG-3
      expressing cancers.

PMID- 15733386
TI  - [Effect of RNA interference on EGF receptor expression of non-small-cell lung
      cancer A549 cell line].
AB  - OBJECTIVE: To investigate changes in biologic properties of non-small-cell lung
      cancer (NSCLC) A549 cells whose EGF receptor (EGFR) expression was suppressed by
      short interference RNA (siRNA). METHODS: A549 cells were transfected with
      synthetic EGFR sequence-specific siRNA by Lipofectamine. EGFR expression was
      examined by Western blot and flow cytometry. The biological features of the
      transfected A549 cells were assessed by cell cycle analysis, colony formation and
      chemosensitivity assay. RESULTS: Sequence-specific siRNAs targeting EGFR
      significantly down-regulated its expression in A549 cells. Cell growth and colony
      formation were inhibited by 85.0% and 63.3%, respectively, as compared to the non
      sequence-specific siRNA treated cells. Decreased EGFR expression was accompanied
      by 12.7% increase in A549 cells in G(0)-G(1) phase and 6.6% decrease in S-phase.
      The EGFR sequence-specific siRNA transfected A549 cells were much more sensitive
      to the cytotoxic effect of cisplatin with a 77.2% decrease in IC(50) compared to
      the non-sequence-specific iRNA transfected A540 cells. CONCLUSION: Down
      regulation of EGFR expression of NSCLC by sequence-specific siRNA may be
      considered as an additional option in the treatment of EGFR over-expressing
      cancers, including NSCLC.

PMID- 15733388
TI  - [Inhibitory effect of ginsenoside-Rg3 on lung metastasis of mouse melanoma
      transfected with ribonuclease inhibitor].
AB  - OBJECTIVE: To investigate the effect of ginsenoside-Rg3 on lung metastasis of
      ribonuclease inhibitor (RI) gene-transfected mouse B16 melanoma. METHODS: C57BL/6
      mice were iv injected with parental or RI-transfected B16 melanoma cells. Lung
      metastasis was assessed by the number of surface tumor nodules. Mice were divided
      into 6 groups. Group I, II and III of mice were given parental, mock-transfected
      and RI-transfected B16 melanoma cells, respectively while in group IV, V and VI,
      Rg3 (1.5 mg/kg, iv q.o.d. x 10) was given to mice bearing parental, mock
      transfected and RI-transfected B16 melanoma, respectively. Micovessel density
      (MVD) of the lung metastatic tumor was assessed by immunohistochemical staining
      of factor VIII-R expression. RESULTS: The number of tumor nodules was
      significantly decreased in mice injected with RI-transfected B16 melanoma (Gp
      III, compared to Gp I and II). Rg3 treatment per se could also decrease the
      number of lung tumor nodules but to a lesser extent (Gp IV and V compared to Gp
      III). However, Rg3 synergized with RI transfection resulting in most significant
      inhibition of lung metastasis (Gp VI). Mice in Gp I and II died within 26 days of
      the experiment, whereas all the mice in Gp VI were alive during the observation
      period of one and one half month. MVD was significantly decreased in the lung
      tumor nodules in mice injected with RI-transfected B16 melanoma. It was further
      decreased when additional Rg3 was given (Gp VI). CONCLUSION: Transfection of
      ribonuclease inhibitor gene significantly reduces the metastatic potential of B16
      melanoma. Ginsenoside-Rg3 has a synergistic effect.

PMID- 15733387
TI  - [Growth inhibitory effect of adriamycin conjugated to single-chain antibody on
      human lung adenocarcinoma in vitro].
AB  - OBJECTIVE: To evaluate the growth inhibitory effect of adriamycin (ADM)
      conjugated to an anti-lung cancer single-chain antibody (ScFv) 2A7-1 on lung
      adenocarcinoma cell line A2 in vitro. METHODS: 2A7-1 cell culture medium was
      concentrated by ultra-filtration (with Amicon P10Z filter), and soluble ScFv was
      purified using RPAS purification kit. ADM was conjugated to 2A7-1 by
      glutaraldehyde. A(280) and A(490) of the conjugate 2A7-1-ADM were determined by
      spectrophotometry and the molar ratio of 2A7-1 to ADM was calculated.
      Immunoreactivity of the conjugate was detected by immunohistochemistry. Its
      growth inhibitory effect on lung adenocarcinoma cell line A2 was determined by
      colony formation assay in vitro. RESULTS: The molar ratio of 2A7-1 to ADM was
      1:3.2. The conjugate strongly reacted with A2 cell. Its growth inhibitory effect
      on A2 cells was 4 times as potent as ADM. CONCLUSION: Adriamycin conjugated to
      anti-lung cancer single-chain antibody 2A7-1 has much higher cytotoxic activity
      than unconjugated adriamycin against human lung adenocarcinoma.

PMID- 15733390
TI  - [Changes in gene expression profiles of hydatidiform mole and choriocarcinoma as
      compared with trophoblast hyperplasia].
AB  - OBJECTIVE: To study the relationship of changes in gene expression profiles of
      hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts. METHODS:
      The differentially expressed genes were analyzed in two pairs of tissues of
      hydatidiform mole versus normal villi, and in two pairs of normal primary culture
      trophoblasts versus JAR cell line of chariocarcinoma, using cDNA microarray
      containing 4096 genes. To confirm the results of cDNA microarray analysis,
      expressions of some up-regulated genes related to DNA synthesis in normal villi,
      hydatidiform mole, and 2 choriocarcinoma cell lines (JAR and JEG-3) were examined
      by immunohistochemistry, immunoblotting and RT-PCR. RESULTS: A total of 89 genes
      were differentially expressed in all hydatidiform moles, accounting for 2.2% of
      the genes arrayed. Of the 89 genes, 24 were up-regulated and 65 were down
      regulated. Compared with normal primary trophoblasts, there were 433 genes up
      regulated and 380 genes down-regulated in JAR cell line. Forty six genes were up
      regulated in both hydatidiform mole and choriocarcinoma, while 13 genes were down
      regulated. Some genes associated with cell proliferative inhibition were
      significantly down-regulated, whereas those associated with cell proliferation,
      malignant transformation, metastasis and drug resistance were highly up
      regulated. The expressions of thymidine kinase 1, the small subunit of
      ribonucleotide reductase (RRM2) were significantly increased in hydatidiform
      mole, JAR and JEG-3 cells. CONCLUSION: Abnormal expression of genes exists in
      hydatidiform mole and choriocarcinoma. Hyperplasia of trophoblasts may be related
      to over-expression of genes coding for synthetic enzymes.

PMID- 15733391
TI  - [Influence of chemotherapy on Th1/Th2 cytokine switching in stomach cancer
      patients].
AB  - OBJECTIVE: To observe the influence of chemotherapy on the switching of Th1/Th2
      cytokines in stomach cancer patients. METHODS: Th1/Th2 cytokine genes expressed
      by peripheral blood mononuclear cells of stomach cancer patients before and after
      chemotherapy were detected by RT-PCR. RESULTS: The expression of Th2 cytokines
      was dominant in patients before chemotherapy, and the dominancy became less
      marked after chemotherapy. CONCLUSION: The immune deviation with Th2 predominance
      in stomach cancer patients has a tendency to become reversed after chemotherapy.

PMID- 15733392
TI  - [Correlation study of expression levels of prostate-specific membrane antigen and
      prostate-specific antigen with Gleason score of prostate carcinoma].
AB  - OBJECTIVE: To study the correlation of prostate-specific membrane antigen (PSMA)
      and prostate-specific antigen (PSA) expression with Gleason score of prostate
      carcinoma. METHODS: Monoclonal antibodies against epitopes of PSMA extracellular
      domain were prepared, with which the expression of PSMA of prostate carcinoma
      (PC) was determined by immunohistochemical staining. Correlation of its
      expression with Gleason score of PC was statistically analyzed, and compared with
      that of PSA. RESULTS: Eight hybridoma cell lines secreting monoclonal antibodies
      specific for PSMA were prepared. PSMA expression level was positively correlated
      with Gleason score. In poorly differentiated prostate carcinoma, the expression
      intensity of PSMA was higher than that of medium-and well-differentiated prostate
      carcinoma (P < 0.01). However, there was no correlation between level of PSA
      expression and Gleason score (P > 0.05). CONCLUSION: PSMA expression level may be
      used as a useful surrogate marker in Gleason grading of prostate carcinoma. It
      may be a more suitable target than PSA in antibody mediated immunotherapy against
      poorly differentiated prostate carcinoma which is usually not sensitive to
      hormonal therapy.

PMID- 15733394
TI  - [IRESSA in the treatment of advanced non-small-cell lung cancer patients who
      failed to respond previous chemotherapy].
AB  - OBJECTIVE: To evaluate the antitumor efficacy, time to tumor progression (TTP)
      and toxicity of Iressa (ZD1839)-a selective epidermal growth factor receptor
      tyrosine kinase inhibitor in advanced non-small-cell lung cancer (NSCLC) patients
      who have failed to respond previous chemotherapy. METHODS: Fifty-two patients
      with grade IV NSCLC previously treated with chemotherapy (77.0% of patients after
      second line therapy) received 250 mg of Iressa orally once daily until disease
      progression or development of intolerable toxic reaction. They were required to
      receive tumor-evaluation before the treatment, one month after Iressa
      administration and every other month thereafter. RESULTS: Without complete
      regression being observed, partial response (PR) rate was 21.2% (11/52), stable
      disease (SD) 32.7% (17/52), disease control rate (PR + SD) 53.8%, progression of
      disease (PD) 46.2% (24/52); median time to tumor progression (TTP) was 3.5 month.
      Among them, 22 patients were followed up over one year and the 1-year survival
      rate was 31.8%. Symptomatic improvement rate was 52.9%. The most common adverse
      effects were skin reactions and diarrhea which were generally mild (grade 1 or
      2). Only one patient withdrew from the trial because of grade III hepatic
      toxicity with increase in ALT and AST. CONCLUSION: Iressa has significant
      antitumor activity in advanced NSCLC patients who have previously failed in
      second or third line chemotherapy. It greatly alleviates tumor related symptoms.
      Adverse effects are generally tolerable. IRESSA is suitable for patients with
      poor performance status (ECOG > 2).

PMID- 15733393
TI  - [Clinical trial on ibandronate in patients with tumor-associated hypercalcemia].
AB  - OBJECTIVE: Ibandronate, a third generation bisphosphonate, inhibits bone
      resorption in human and animal studies. This study is to evaluate the efficacy
      and safety of ibandronate as a single agent in patients with tumor-associated
      hypercalcemia. METHODS: An open, multicenter, non-controlled clinical trial was
      conducted in 22 patients. The patients received 2 mg ibandronate intravenously if
      the corrected calcium was less than 3.0 mmol/L but more than 2.7 mmol/L; they
      received 4 mg ibandronate iv if corrected calcium was more than 3.0 mmol/L.
      RESULTS: There was 100% efficacy in these two dose groups but the calcium
      correcting effect was more pronounced in the 4-mg dose group than the 2-mg dose
      group. The most common adverse reactions were fever and skin itching with an
      incidence of 4.5%. CONCLUSION: Ibandronate is active in patients with tumor
      associated hypercalcemia and the adverse effects are well tolerated.

PMID- 15733396
TI  - [Oxaliplatin plus capecitabine as a second line chemotherapy for patients with
      advanced gastric cancer].
AB  - OBJECTIVE: To evaluate the effect and toxicity of oxaliplatin combined with
      capecitabine (Xeloda) as a second-line chemotherapy regimen for patients with
      advanced gastric cancer. METHODS: Twenty-four patients with advanced gastric
      cancer who had been treated by multiple chemotherapy regimens presenting poor
      responses were allotted. LX regimen (oxaliplatin 85 mg/m(2) in 2-hour infusion on
      D1 and D15, capecitabine 1250 mg/m(2)/d divided in two daily doses given from D1
      to D14) was adopted. The cycles were repeated every 28 days. All patients
      received two or more cycles. RESULTS: All 24 patients were evaluated after having
      received 2 to 6 cycles of chemotherapy, totally 92 cycles. The overall response
      rate was 29.2% (including 2 CR, 5 PR, 10 NC and 7 PD). The time to tumor
      progression (TTP) was 2 to 18 months (median 5 months), and duration of remission
      was 4 to 14 months (median 8 months). The major toxicities were bone marrow
      suppression and nausea/vomiting. CONCLUSION: Oxaliplatin combined with capitabine
      is effective as a secondary line regimen for patients with advanced gastric
      cancer. This protocol is active and well tolerated. Further clinical studies are
      warranted.

PMID- 15733397
TI  - [Short-term effects of chemotherapy with combination of hydroxycamptothecine and
      oxaliplatin in the treatment of advanced digestive tract cancers].
AB  - OBJECTIVE: To evaluate the short-term therapeutic effects and side effects of
      combined hydroxycamptothecine and oxaliplatin in the treatment of advanced
      digestive tract cancers. METHODS: Thirty patients suffering from advanced
      digestive tract tumors including gastric cancer 8, colorectal cancer 20,
      cholecystic cancer 1 and malignant fibroadenoma 1 were studied. They were treated
      with hydroxycamptothecine plus oxaliplatin for 2 cycles with interval of 21 days.
      RESULTS: The complete response, partial response, stable disease and progressive
      disease rates were 3.3% (1/30), 36.7% (11/30), 53.3% (15/30) and 6.7% (3/30)
      respectively with an overall response rate (CR + PR) of 40.0% (12/30). In the
      whole 77 cycles, leukocytopenia was observed in 34 cycles (44.2%) and 19 cycles
      (55.9%) at grades III and IV. Diarrhea developed in 42 cycles (54.5%) and 20
      cycles (47.6%) grades III and IV. The other side effects were fever, alopecia,
      nausea and vomiting, constipation, hepatic and renal function abnormity and
      neuritis. CONCLUSION: Satisfactory response rate is obtainable in advanced
      colorectal cancer as treated by hydroxycamptothecine plus oxaliplatin. The
      toxicity consists of severe leukocytopenia and diarrhea.

PMID- 15733398
TI  - [Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma
      of esophagus].
AB  - OBJECTIVE: Paclitaxel was used in a phase II trial in combination with cisplatin
      for esophageal cancer. The anti-tumor response, toxicity and survival of the
      treated patients were evaluated. METHODS: Thirty patients with advanced,
      unresectable, or complicated with metastasis were allotted, twenty-seven patients
      had no prior chemotherapy while 3 patients had received adjuvant chemotherapy.
      Patients were given paclitaxel 175 mg/m(2) by 3-hour infusion on D1, and
      cisplatin 40 mg/m(2) daily on D2 and D3. Granulocyte colony-stimulating factor (G
      CSF) was not routinely administered unless the patient had neutropenia. Treatment
      was recycled every 21 days. RESULTS: Thirty patients (male/female, 28/2; median
      age 58) completed a median of 3 cycles and 27 patients were evaluable for
      response. Major objective responses were observed in 16 patients (59.3%; 95%
      confidence interval, 38.9% to 75.5%), including 5 complete responses (18.5%) and
      11 partial responses (40.7%). The median time to tumor progression was 5.0 months
      (range, 1 to 23 months). The median actuarial survival was 9.7 months (range, 1
      to 23 months). Twenty-eight patients were assessable for toxicity. The most
      common nonhematologic toxicity was alopecia. Grade 3 to 4 neutropenia was
      observed in 17.9% of the patients. Toxicity was manageable with dose attenuation
      and G-CSF support. CONCLUSION: The combination of paclitaxel and cisplatin can be
      considered as a main regimen in the treatment of advanced esophageal cancer.

PMID- 15733399
TI  - [Bilateral primary breast cancer: a report of 217 cases].
AB  - OBJECTIVE: To report the clinical and pathological characteristics of bilateral
      primary breast cancer (BPBC) in comparison with unilateral primary breast cancer
      (UPBC). METHODS: A retrospect database of primary breast cancer patients admitted
      to the Cancer Hospital from March 1967 through May 2003 was analyzed. RESULTS: A
      total of 10,470 primary breast cancer patients were treated, among which 271
      patients had bilateral primary tumors with an incidence of 2.1%. Most of the
      BPBC, developed both synchronously (sBPBC, incidence rate: 0.6%) and
      metachronously (mBPBC, incidence rate: 1.5%), were diagnosed in premenopausal
      women with an average age of 48. In the latter cases, the median time interval
      between their occurrences was 57.6 months. The median survival time for patients
      with sBPBC and mBPBC was 29.6 months and 27.8 months, respectively. There was no
      statistical difference in survival rate between the 2 groups of patients. Nor was
      menopausal status related to survival. In mBPBC patients, when the occurrence of
      the second breast cancer was taken as the beginning of prognostic analysis, the
      prognosis of BPBC patients was worse than those with unilateral involvement.
      CONCLUSION: Prognosis of patients with bilateral primary breast cancer is poor.
      In mBPBC patients whose breast cancers appear one after the other, meticulous
      follow-up is needed after resection of tumor on one side to early detect
      development of cancer of the countralateral breast especially within 5 years.

PMID- 15733401
TI  - [Effect of heparin on fetal growth restriction].
AB  - OBJECTIVE: To investigate the clinical effect and safety of heparin in treating
      fetal growth restriction (FGR). METHODS: A total of 107 women diagnosed with FGR
      were randomized into three groups. Group 1 (standard heparin group, n = 37)
      received 50 - 75 mg standard heparin added to 500 ml 5% glucose sodium chloride,
      infused intravenously in 6 - 8 hours. Group 2 (low molecular weight heparin
      group, n = 31) received 0.2 - 0.4 ml low molecular weight heparin given by
      subcutaneous injection. Control group (n = 39) received 20 ml dan-shen added to
      500 ml low-molecular-weight dextran infused intravenously. Fetal growth indices,
      biophysical score, umbilical artery blood flow, count of platelet (PLT),
      prothrombin time (PT), activated partial thromboplastin time (APTT), 1-minute
      Apgar score, body weight and gestational age of the neonates were measured.
      Babies prognosis was followed-up. RESULTS: (1) Height of fundus of uterus was
      obviously increased per week in the groups of standard heparin (0.7 +/- 0.6) cm
      and low molecular weight heparin [(0.7 +/- 0.6) cm]] vs. control group [(0.5 +/-
      0.4) cm, P < 0.05]. Biparietal diameter of fetus increased in standard heparin
      [(2.4 +/- 0.7) mm] and low molecular weight heparin [(2.5 +/- 0.8) mm] groups vs.
      control [(1.7 +/- 0.6) mm, P < 0.05]. The femur length, head circumference and
      abdominal circumference of fetus were significantly longer in heparin treated
      patients than in control group (P < 0.05). (2) Biophysical score improved in
      groups of standard heparin (9.7 +/- 0.8) and low molecular weight heparin (9.6 +/
      0.6) vs. control group (8.9 +/- 0.7) (P < 0.05). (3) Umbilical blood S/D ratio
      decreased in standard heparin (2.5 +/- 0.5) and low molecular weight heparin (2.4
      +/- 0.5) groups vs. control group (2.9 +/- 0.6) (P < 0.05). Pulsatile index (PI)
      and resistance index (RI) were significantly lower also (P < 0.05).(4) Rate of
      one minute Apgar score (8 - 10) was 86% in group 1, 87% in group 2 and 74% in
      control group, respectively. Body weight of the neonates was significantly
      increased in group 1(3100 +/- 256 g) and in group 2 [(3080 +/- 225) g] vs. [(2580
      +/- 304) g] in control group (P < 0.05). Gestational age was prolonged in group 1
      [(38 +/- 3) w] and group 2 [(38 +/- 4) w] vs. control group [(37 +/- 4) w, P <
      0.05]. (5) Incidence of term small for gestational age infant in groups of
      standard heparin and low molecular weight heparin was 5% and 6%, respectively,
      significantly lower than those in the control group (18%) (P < 0.05). (6) No
      difference was shown in PLT, PT and APTT before and after heparin treatment (P >
      0.05). (7) There was no difference in fetal growth indices, biophysical score,
      umbilical blood, neonatal outcome between standard heparin and low molecular
      heparin groups. CONCLUSIONS: Heparin can improve placenta function and obviously
      increase body weight of fetuses and neonates. It is safe for both pregnant women
      and their fetuses.

PMID- 15733402
TI  - [Diagnosis and management of uterine arteriovenous fistula with massive vaginal
      bleeding].
AB  - OBJECTIVE: To study the clinical manifestation, diagnosis, management and
      prognosis of uterine arteriovenous fistula with massive vaginal bleeding. METHOD:
      The clinical records of 15 patients who satisfied the diagnostic criteria were
      retrospectively analyzed. RESULTS: All patients had massive vaginal bleeding,
      with a history of caesarean section, curettage or gynecologic carcinoma. The
      disease could be diagnosed by angiography or color Doppler ultrasound. Vaginal
      bleeding was aggravated by dilation and curettage. Fourteen patients were treated
      with uterine artery embolization, and no complications occurred postembolization.
      Of the eleven successful embolizations, all patients returned normal menstrual
      cycling. Five of these patients became pregnant later. CONCLUSIONS: Uterine
      arteriovenous fistula is a rare and potentially life threatening disease. Uterine
      artery embolization is a safe and effective treatment for this disease, and it
      can preserve normal function of uterus and ovaries.

PMID- 15733403
TI  - [A clinical study of pelvic floor electrical stimulation in treatment of
      overactive bladder].
AB  - OBJECTIVE: To observe the efficacy of electrical stimulation in treatment of
      overactive bladder (OAB). METHODS: Patients (n = 60) with overactive bladder were
      randomly divided into 2 groups. Electrical stimulation group (n = 35) used an
      instrument for electrical stimulation through a special vagina or rectum probe
      transfer current (8-70 mA), for 20 min, qd, for 20-30 times. Medical group (n =
      25) received oral tolterodine 2 mg, bid, for 2-4 weeks. RESULTS: The total
      effective rate and cure rate were 74%, 37% in electrical stimulation group and
      76%, 40% in medical group, respectively, showing no significant difference
      between two groups (P > 0.05). While patients' satisfactory rate was
      significantly higher in electrical stimulation group than in medical group (P <
      0.05). Side effects were more commonly seen with tolterodine. CONCLUSIONS:
      Electrical nerve stimulation is effective and safe for overactive bladder.
      Further studies are needed to show the long term efficacy and cost-effectiveness.

PMID- 15733404
TI  - [Ovarian insulin resistance and insulin sensitizer effect on polycystic ovary
      syndrome].
AB  - OBJECTIVE: To explore the molecular defects of insulin signalling in polycystic
      ovary and in vitro effects of troglitazone, one of the insulin sensitizers
      thiazolidinediones on polycystic ovary syndrome (PCOS). METHOD: The metabolic and
      mitogenic effects of insulin and insulin-like growth factor 1 (IGF-1) were
      examined in cultured human ovarian luteinizing granulosa cells from PCOS (n = 11)
      and normally ovulatory (as control, n = 33) women with vehicle or troglitazone (1
      microg/ml). RESULTS: Basal rates were similar, but there were significant
      decreases in insulin-stimulated glucose incorporation into glycogen in PCOS
      cells, a metabolic action of insulin. However, IGF-1 response was found to be
      about twice greater in PCOS cells at all experimental concentrations with respect
      to thymidine incorporation compared to control cells, a mitogenic action.
      Troglitazone increased 2-3 fold the insulin-induced glycogen synthesis, but
      reduced the IGF-1 augmented responses of DNA synthesis in PCOS cells to within
      the range of control granulosa cells. As compared with control, PCOS granulosa
      cells had higher insulin receptor substrate 1 (IRS -1) expression, but lower IRS
      2 expression. IRS-2 protein levels were increased and IRS-1 levels were reduced
      by troglitazone treatment, with a greater extent in the former. CONCLUSIONS:
      There is a selective defect in insulin actions in PCOS granulosa cells,
      suggesting ovarian insulin resistance and this metabolic phenotype is associated
      with an enhanced IGF-1 mitogenic potential. Troglitazone could divergently alter
      signal protein expressions and thus insulin actions, as an ovarian insulin
      sensitizer and mitogen/steroidogenic inhibitor in PCOS.

PMID- 15733405
TI  - [Expressions of matrix metalloproteinase-9 and tissue inhibitor of
      metalloproteinase-1 in ectopic and eutopic endometrium].
AB  - OBJECTIVE: To study the expression of matrix metalloproteinase-9(MMP-9) and
      tissue inhibitor of metalloproteinase-1 (TIMP-1) in ectopic and eutopic
      endometrium in patients with endometriosis. METHODS: The expressions of MMP-9 and
      TIMP-1 in ectopic and eutopic endometrium were detected by immunohistochemistry
      streptavidin-biotin peroxidase (SP) method in 45 patients with endometriosis
      (study group) and in 32 patients with uterine fibroid (control group). RESULTS:
      In the ectopic and eutopic endometrium of group and in the control group
      endometrium, the expression of MMP-9 was respectively 0.381, 0.336 and 0.276; the
      expression of TIMP-1 was respectively 0.239, 0.253, 0.267. As a result, the ratio
      of MMP-9/TIMP-1 in ectopic and eutopic endometrium of study group and in the
      control group endometrium was respectively 1.594, 1.293, 1.034. The difference of
      MMP-9, MMP-9/TIMP-1 in ectopic and eutopic and the control group endometrium was
      markedly significant (P < 0.01 or P < 0.05). The difference of the expression of
      TIMP-1 between ectopic and the control group endometrium was also markedly
      significant (P < 0.01). Higher expression of MMP-9 and lower expression of TIMP-1
      in ectopic endometrium and higher expression of MMP-9 in eutopic endometrium
      occurred in the whole menses period, in which higher expression of MMP-9 in
      ectopic endometrium than in eutopic endometrium only took place in proliferative
      phase. CONCLUSION: The change of expression of MMP-9 and TIMP-1 in ectopic
      endometrium may be related to the pathogenesis of endometriosis.

PMID- 15733406
TI  - [Studies on safety of cordocentesis guided by transabdominal ultrasound for
      prenatal diagnosis].
AB  - OBJECTIVE: To assess the safety and efficacy of diagnostic cordocentesis during
      pregnancy. METHODS: During March 1990 to June 2003, 2403 consecutive
      cordocenteses were performed under transabdominal ultrasound guidance at
      Guangzhou Women and Children's Hospital. The results of each procedure was
      prospectively collected and subsequently analysed in terms of operational
      complications and pregnancy outcomes. RESULTS: Success rate of cordocentesis:
      totally 2368 procedures (98.5%) were done successfully at the first attempt, and
      35(1.5%) required repeated cordocentesis, 16 of which were performed successfully
      at second attempt. Duration of cordocentesis: In 75.5% cases, the procedure was
      completed in less than 5 min, and in 93.0% cases in less than 10 min.
      COMPLICATIONS: Transient bleeding at puncture site was observed in 315 cases
      (13.1%), transient fetal bradycardia in 125 cases (5.2%), and chorioamnionitis in
      2 cases (0.1%). Pregnancy outcomes: The total fetal loss rate was 0.8% (18 cases
      of abortions). The rate of premature birth after cordocentesis was 0.2% (4
      cases). CONCLUSION: Cordocentesis during pregnancy is a useful, relatively safe,
      and effective procedure for prenatal diagnosis.

PMID- 15733407
TI  - [Study on the relationship between regulatory T cells and unexplained recurrent
      spontaneous abortion].
AB  - OBJECTIVE: To investigate the relationship between CD(4)(+)CD(25)(+) regulatory T
      cells (CD(4)(+)CD(25)(+)Tr) and unexplained recurrent spontaneous abortion
      (URSA). METHODS: The expression rate of CD(4)(+)CD(25)(+)Tr in peripheral blood
      was determined by double-label flow cytometric analysis. The samples were taken
      from 20 normal non-pregnancy women, 17 URSA women and 20 normal pregnancy women.
      RESULTS: The expression frequency of CD(4)(+)CD(25)(+)Tr cells was decreased
      significantly (P < 0.01) in URSA women [(11.9 +/- 2.7)%] than that in normal non
      pregnancy women [(15.2 +/- 3.0)%], however, there was no significant difference
      between normal pregnancy women [(14.4 +/- 4.8)%] and normal non-pregnancy women
      (P > 0.05). CONCLUSION: The results suggest that downregulation of
      CD(4)(+)CD(25)(+)Tr may be associated with URSA.

PMID- 15733423
TI  - [Second generation of endometrium ablation].

PMID- 15733424
TI  - [Progress in progestogen and mechanism of endometriosis].

PMID- 15733425
TI  - [Pregnancy complicated with giant hydronephrosis].

PMID- 15733427
TI  - [Strick observance to the indication in promotion of implantation of
      hydroxyapatite].

PMID- 15733428
TI  - [Study on differential diagnosis between MALT-type lymphoma and reactive lymphoid
      hyperplasia of the ocular adnexa].
AB  - OBJECTIVE: To study the methods of differential diagnosis between mucosa
      associated lymphoid tissue (MALT) type lymphoma and reactive lymphoid hyperplasia
      in ocular adnexa. METHODS: The clinical, morphologic, immunohistochemical, and
      molecular biologic (polymerase chain reaction [PCR]) studies were performed on 29
      patients with MALT-type lymphoma and 8 patients with reactive lymphoid
      hyperplasia of the ocular adnexa. RESULTS: 29 cases with MALT-type lymphoma
      expressed B-cell markers and but T-cell makers, whereas 8 cases of reactive
      lymphoid hyperplasia all expressed B and T cell markers and the positive rate of
      T-cell marker was up to 30%. immunohistochemistry staining showed 11 cases were
      positive for immunoglobin light chain (kappa or lambda), however it was positive
      in one chain of the immunoglobin in 15 cases of MALT type lymphoma by PCR. No
      significant difference in the clinical characteristics was observed between the
      MALT type lymphoma and reactive lymphoid hyperplasia in ocular adnexa.
      CONCLUSION: Immunohistochemical analysis and PCR are helpful in confirming the
      diagnosis between the MALT-lymphoma and the reactive lymphoid hyperplasia.

PMID- 15733429
TI  - [Surgical treatment of orbital and periorbital fibrous dysplasia].
AB  - OBJECTIVE: To explore the surgical approaches to obtain good aesthetic and
      functional results in the management of orbital and periorbital fibrous dysplasia
      and related deformities. METHODS: Ten cases of orbital and periorbital fibrous
      dysplasia were treated surgically. The location, extension and shape of the
      lesions were identified based on X-ray examination and two and three dimensions
      CT examinations preoperatively. According to the type of the lesion, different
      approaches were used to excise the lesion and to reconstruct the orbit. The
      lesions were radically or partially excised through bicoronal, intraoral and
      subciliary approach; the orbit was reconstructed with autogenous outer or inner
      table of calvarium, outer table of mandible, Medpor and prefabricated individual
      titanic implants. RESULTS: In 10 cases treated surgically, radical excision was
      employed in 4 cases and partial excision in 6 cases. Autogenous inner table of
      calvarium was used in 2 cases, Medpor in 2 cases, outer table of mandible in 1
      case, and titanic meshwork and prefabricated individual titanic implants in 4
      cases to reconstruct the orbit. After the treatment, all patients obtained
      satisfactory aesthetic and functional results. CONCLUSIONS: Carefully planed
      surgical approaches with methods for preventing the complications can be used for
      the treatment of orbital and periorbital fibrous dysplasia and obtaining
      satisfactory aesthetic and functional results.

PMID- 15733430
TI  - [Traumatic Rollel's syndrome treated with decompression of orbital apex].
AB  - OBJECTIVE: To observe the efficiency of decompression of orbital apex operation
      for the treatment of traumatic Rollel's syndrome. METHODS: Eleven patients with
      Rollel's syndrome were operated using two different approaches of decompression
      of orbital apex according to the location of the lesion. Five cases were treated
      by trans-frontal approach and 6 cases by trans-pterion approach. For the purpose
      of evaluation, the postoperative outcome of visual acuity was classified into
      five grades: Non-light perception, light perception, hand motion, finger counter
      and acuity chart. The visual acuity improvement reaching 1 grade or more was
      defined as effective and less than 1 grade as inefficient. The improvement of
      nerve injuries in superior orbital fissure was also evaluated, patients with
      recover of 2 or more nerves was defined as effective. RESULTS: Visual acuity: 3
      cases (50%) were classified as effective in non-light perception group, the
      remaining 5 cases who had residual vision before operation all improved to
      various extents. The eye position in cases with exophthalmos was return to normal
      after operation. Injured nerves were recovered in all 11 cases. CONCLUSIONS:
      Decompression of orbital apex is an effective treatment for patients with
      Rollel's syndrome and the craniotomy approach can treat the combined brain
      injury. The recovery after operation is correlated with the timing of surgery,
      the approach of the operation and also related with the severity of the nerve
      injury.

PMID- 15733431
TI  - [Krypton laser photocoagulation at low power setting for age-related macular
      degeneration complicated with subfoveal choroidal neovascularization].
AB  - OBJECTIVE: To evaluate the efficacy of krypton laser photocoagulation for
      treatment of age-related macular degeneration (AMD) complicated with mainly
      subfoveal classic choroidal neovascularization (CNV). METHODS: Seventeen eyes of
      17 cases, aged 50 - 74 years (averaged 60.8 years) with mainly subfoveal classic
      choroidal neovascularization were treated with krypton laser at lower power
      setting. The treatment was completed in one session. Another course of treatment
      was given 4 weeks later if there was active leakage demonstrated at the CNV area.
      Visual acuity, anterior segment and fundus examination, perimetry test, fundus
      fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were
      performed before and after treatment. The follow-up period was 3.5 years on
      average (1 - 8 years). RESULTS: There was no immediately decrease of visual
      acuity after treatment. All treated eyes showed absorption of hemorrhages and/or
      exudates and diminished leakages. Visual acuity was stable in 8 eyes; improved in
      6 eyes (>/= 2 lines), and decreased in 3 eyes (</= 2 lines). The central scotoma
      showed no significant changes after the treatment. Closure of CNV was confirmed
      on FFA/ICGA and no recurrence was found in 9 cases during 3 years follow-up.
      CONCLUSION: Krypton laser photocoagulation at low power setting is an effective
      treatment for AMD with mainly classic subfoveal choroidal neovascularization.

PMID- 15733432
TI  - [Visual outcome with the array multifocal intraocular lens].
AB  - OBJECTIVE: To evaluate the visual outcome of Array IOL, and examine the location
      of the lens. METHODS: 255 eyes in 196 patients received phaco and IOL
      implantation were randomized as test group 121 eyes (Array IOL) and case control
      group 134 eyes (monofocal Hydroview IOL). Postoperative examination included
      distance and near, uncorrected and corrected visual acuity, refractive results,
      and measurement of corneal curvature. Follow-up period ranged from three months
      to one year. RESULTS: Three months after surgery, 97.2% eyes (107/110) in test
      group with Array IOL had a distance visual acuity >/= 0.5, and in 24.5% (27/110)
      >/= 1.0. The difference was not significant (P > 0.05). 84.6% eyes (93/110) in
      test group had an uncorrected near acuity >/= 0.5 and 20.0% (22/110) >/= 1.0. The
      difference was significant (P < 0.01). The rate of wearing spectacles was 33.3%
      in test group and 90% in case control group. One month after surgery, 6 eyes in
      test group with haptic asymmetric location were not affected with visual
      recovery. The surgery-induced astigmatism in test group was 0.31 D, and no visual
      impairment appeared in both groups. Posterior capsule opacification was seen in 6
      eyes in test group and 12 in case control group. CONCLUSION: The implantation of
      Array IOL not only has a good distance uncorrected visual acuity, but also with
      better near visual acuity. Also this surgery is safe, reliable and no special
      complication-induced.

PMID- 15733433
TI  - [Long-term evaluation of laser in situ keratomileusis for extremely high myopia].
AB  - OBJECTIVE: To evaluate the long-term efficacy and safety of laser in situ
      keratomileusis (LASIK) for extremely high myopia (with a preoperative refraction
      more than -10.00 diopters). METHODS: 173 eyes of 99 patients with a mean
      spherical equivalent (SE) of (-13.70 +/- 3.60) D (range -10.00 approximately
      23.50 D), including 41 eyes with more than -15.00 D, were treated with LASIK and
      followed up for more than 18 months. The examinations included slitlamp
      microscopy, fundus examination, Orbscan II corneal topography system, tonometry,
      pachymetry, cycloplegic and subjective refraction. RESULTS: At 18 months
      postoperatively, the uncorrected visual acuity (UCVA) was 0.5 or better in 148
      eyes (85.6%), and the best spectacle-corrected visual acuity (BSCVA) remained the
      same or increased in 147 eyes (84.4%). No eye lost more than two lines of BSCVA.
      109 eyes (63.0%) were within +/- 1.00 D of emmetropia. The percentage was 73.5%
      and 29.3% in eyes with a preoperative SE of less than -14.75 D and more than 
      15.00 D, respectively. Postoperatively, the posterior corneal surface bulge was
      detected in all eyes. The mean elevation of the posterior corneal surface against
      the best-fit sphere was (0.029 +/- 0.010) mm preoperatively, (0.069 +/- 0.031) mm
      at 3 months, (0.065 +/- 0.025) mm at 18 months. At final follow-up, corneal flap
      folds were found in 2 eyes, and 6 patients (10 eyes) complained of glare or
      decreased scotopic vision. CONCLUSION: LASIK appeared to be an effective and safe
      treatment for correction of extremely high myopia. Meanwhile the candidates
      should be carefully screened.

PMID- 15733434
TI  - [Rapid pathogens diagnosis of infected keratitis and endophthalmitis using two
      steps polymerase chain reaction].
AB  - OBJECTIVE: To establish a rapid diagnosis technique of the pathogens of infected
      keratitis and endophthalmitis. METHODS: Fifty-one corneal scraping, tear and 16
      vitreous specimens were obtained from 67 cases of infected keratitis and
      endophthalmitis. Multiplex polymerase chain reaction (MPCR) was performed to
      differentiate the genes of bacteria, fungi and HSV using their own universal
      primers. Special-primers PCR were carried out for MPCR positive specimens to
      detect the genes of common bacteria and fungi respectively. The results were
      compared with microbe culture and clinical diagnosis. RESULTS: In 67 clinical
      samples, 52 (77.6%) were positive at least one kind of pathogen by MPCR (two
      positive pathogens were 8 cases). SPCR revealed that 7 bacteria (25.0%) out of 28
      bacteria positive specimens were Staphylococcus aureus, Streptococcus pneumoniae,
      Pseudomonas aeruginosa. Eight fungi (53.3%)of 15 fungi positive specimens was
      Candida, Aspergillus, Fusarium. The culture positive rates were 31.3% (21 cases),
      among them 1 case was found positive for two pathogens. MPCR positive rate was
      statistically higher than the rate that in culture (chi(2) = 13.50, P < 0.005).
      The kinds of bacteria and fungi of SPCR positive were as the same as bacteria and
      fungi of culture positive. Consistency of clinical diagnosis and experimental
      evidences of infected keratitis was 54.8%. The time for microbe culture needs 72
      to 96 hours, but MPCR and SPCR needs 8 hours. CONCLUSION: Two steps PCR is rapid,
      sensitive method to detect the pathogens of infected keratitis and
      endophthalmitis.

PMID- 15733435
TI  - [Gene mapping of a pedigree with autosomal dominant congenital cataract].
AB  - OBJECTIVE: To map the gene for autosomal dominant congenital cataract (ADCC) in a
      Chinese family. METHODS: Blood samples were collected from 14 members of this
      family. Linkage analysis was carried out using short tandem repeat polymorphism
      (STRP) in close proximity to genes and loci previously reported involving in
      human cataract. Two-point linkage analysis lod scores were calculated. RESULTS:
      The mutation gene locus in this pedigree was mapped to 17q, an 11.78-cM interval
      between markers D17S1288 and D17S933. Significant positive maximum LOD scores
      (Z(max)) at recombination fraction (theta) 0, were obtained for markers D17S805
      (Z(max) = 2.03), D17S1294 (Z(max) = 2.49), and D17S1293 (Z(max) = 2.22).
      CONCLUSIONS: The mutation gene in this ADCC pedigree is located at chromosome
      17q. This is the first report of an autosomal dominant congenital nuclear
      cataracts located at this locus. This result will be helpful for further studying
      of the pathogenesis of cataract.

PMID- 15733436
TI  - [Novel mutation of fibrillin 1 gene cause ectopia lentis in a Chinese family].
AB  - OBJECTIVE: To identify the mutation gene of a Chinese family with ectopia lentis.
      METHODS: Clinical observation and pedigree analysis were undertaken in a family
      with ectopia lentis. Venous blood was drawn from 7 affected and 3 unaffected
      subjects. Genomic DNA was extracted. Linkage to the fibrillin 1 (FBN1) locus was
      not excluded. Mutation of this gene was screened by PCR of FBN1 exons and direct
      sequencing. PCR and restrictive endonuclease digestion were applied for
      population study. RESULTS: A missense mutation G640A in exon six of FBN1 gene was
      identified in affected patients of this Chinese family. The correspond amino acid
      change was Gly214Ser. Restrictive endonuclease site Eag I was eliminated. This
      mutation was not found in unaffected family members of this family nor it was
      found among 50 unrelated normal controls. CONCLUSIONS: A novel mutation of FBN1
      gene with Glycine to Serine change is responsible for the ectopia lentis patients
      in a Chinese family.

PMID- 15733437
TI  - [The pathway of bFGF induced changes of calcium in cultured human lens epithelial
      cells].
AB  - OBJECTIVE: To investigate the pathway of basic fibroblast growth factor (bFGF)
      induced changes of calcium in a human lens epithelial cell line LEC-B3. METHODS:
      The 3rd passage of LEC-B3 cells was used in the present studies. bFGF (10
      microg/L), caffeine (10 mmol/L), ryanodine (10 mmol/L), procaine (50 mmol/L) and
      genistein (0.5 mmol/L) were added to the culture medium. Changes of calcium
      concentration were observed and analyzed with laser scanning confocal microscope.
      RESULTS: bFGF (10 microg/L) could induce a prompt increase of calcium
      concentration when cells culturing in culture medium with or without calcium. No
      obvious difference of calcium concentration could be observed between these two
      conditions except that the amplitude of increase of calcium concentration under
      calcium free solutions was slightly higher than that in medium with calcium. Both
      50 mmol/L procaine and 10 mmol/L ryanodine partially inhibited the calcium
      increase induced by bFGF. After the addition of 10 mmol/L caffeine, 10 microg/L
      bFGF could not induce a significant increase of calcium. Genistein at 0.5 mmol/L
      significantly inhibited bFGF induced changes of calcium. CONCLUSIONS: bFGF
      inducing calcium ion concentration increase mainly depends on TPK pathway. Most
      of the calcium ions come from the release of intracellular calcium pools in human
      lens epithelial cell. Both the IP(3R) and RyR take part in the action, while
      IP(3R) is the more important factor.

PMID- 15733438
TI  - [Low-intensity microwave blockes cell cycle and regulate cell cycle related gene
      expression in rabbit lens epithelial cells].
AB  - OBJECTIVE: To study the cell cycle arrest induced by different doses of microwave
      in cultured rabbit lens epithelial cells (RLECs) and its effects on the related
      gene expression of P21(WAF1), P27(Kip1) and c-myc. METHODS: Cultured rabbit lens
      epithelial cells were exposed to microwave radiation with frequency of 2450 MHz
      and power density of 0.10 mW/cm(2) (A group), 0.25 mW/cm(2) (B group), 0.50
      mW/cm(2) (C group), 1.00 mW/cm(2) (D group) and 2.00 mW/cm(2) (E group) for 8
      hours. The morphological change of RLECs was observed under microscope, effects
      of microwave radiation on RLECs cell cycle were measured by flow cytometry.
      Expression of P21(WAF1), P27(Kip1) and c-myc were evaluated by western blot after
      2.00 mW/cm(2) microwave radiation for 4 hours, 6 hours and 8 hours respectively.
      All the results were compared with F group, which was as controls without
      microwave radiation. RESULTS: 8 hours after radiation, RLECs of C, D and E groups
      showed RLECs cell swelling, congregation and detachment, the percentage of cells
      in G(0)/G(1) phase obviously was increased (P < 0.01). No obvious change could be
      detected in 0.10 mW/cm(2) and 0.25 mW/cm(2) microwave groups. The gene expression
      of P27(Kip1) was increased and c-myc was decreased after 2.00 mW/cm(2) radiation,
      it did not affect the gene expression of P21(WAF1). CONCLUSION: Microwave
      exceeding 0.50 mW/cm(2) can block RLECs cell cycle at G(0)/G(1) phase, which may
      be related to regulation of P27(Kip1) and c-myc expression, but not P21(WAF1).

PMID- 15733449
TI  - [The applications of the radiotherapy in the orbital disease].

PMID- 15733450
TI  - [Evaluation of the postoperative quality of life in the elderly over 80 years old
      who underwent hip hemiarthroplasty for femoral neck fracture].
AB  - OBJECTIVE: To evaluate the postoperative quality of life of aged patients (> 80
      years old) who underwent hip hemiarthroplasty for femoral neck fracture one year
      ago. METHODS: From February 1995 to February 2001, 52 elderly patients (> 80
      years old) underwent the hip hemiarthroplasty after femoral neck fractures. There
      were 28 males and 24 females, with the average age of 84.2 years old (ranged from
      80 - 95 years old). The fracture type was Garden III or IV, and all the patients
      underwent the hip hemiarthroplasty of domestic prosthesis. Before the operation,
      most of them were accompanied with pre-existed diseases. Harris hip score
      including symptoms and the ability of daily life at the one year after operation
      was adopted for the follow-up. Postoperative A-P and lateral X-ray of hip joint
      in different phase were also assayed. RESULTS: Forty-six patients (88.46%) were
      free of pain and satisfied their operations, only 6 patients (11.54%) complained
      about slight pain. Twenty-four patients (46.2%) were able to walk without any
      assistant, 24 patients (46.2%) managed to walk by walker, 4 patients (7.7%) could
      only lie on the bed or move by wheel chair. Postoperatively, patients with
      neurological diseases such as Parkinson dementia, Senile dementia,
      cerebrovascular diseases got poor result of the quality of life. However, the
      other comorbid diseases such as cardiovascular diseases, diabetes mellitus,
      chronic renal failure, chronic bronchitis did not affect the result. Thirty-eight
      patients had the postoperative X-ray when they were followed up. Postoperatively,
      the X-ray were taken from 3 months to 5 years and 6 months, averaged 54.2 months.
      Sclerotic line were discovered around the shaft of prosthesis only in 3 patients.
      No complications such as femoral head central dislocation or hip osteoarthritis
      were found. CONCLUSION: Operative treatment could be actively adopted for aged
      femoral neck fracture patients without surgical contraindication, which can
      contribute to obtain the motion ability, reduce complication caused by lying in
      bed, and keep a good quality of life.

PMID- 15733451
TI  - [Acetabular component centralization in total hip arthroplasty for acetabular
      dysplasia].
AB  - OBJECTIVE: To explore the correct localization of the acetabular component,
      surgical technique and the outcome in total hip arthroplasty (THA) for acetabular
      dysplasia with secondary osteoarthritis. METHODS: A retrospective review was
      undertaken of 44 hips (38 patients) that had had a total hip arthroplasty for
      acetabular dysplasia with secondary osteoarthritis from September.1989 to April.
      2003. 14 were male (one bilateral) and 24 patients were female (5 bilateral). The
      mean duration of clinical and roentgenographic follow-up was thirty-six months
      (range, eight to one hundred and sixty-eight months), and the mean age of the
      patients was fifty-one years (range, twenty-nine to eighty years). Twelve hips
      were classified as type I; twenty-four as type II; seven as type III; and one as
      type IV, according to the criteria of Crowe. The horizontal location of the
      center of the hip (the distance along the interior drop line extending lateral or
      medial from the inferior point of the teardrop to the perpendicular line dropped
      from the center of the femoral head) was measured. RESULTS: There were 24
      acetabular components that were placed in the centralized position and the other
      20 in no deepen placement post-operatively. At the most recent follow-up, the
      mean Harris hip score was 90.2, 86.3 for the centralized position and the
      undeepen placement hips respectively, there was a significant difference between
      these two groups. CONCLUSIONS: In order to obtain the stability of acetabular
      component, deepen acetabular reaming is necessary for the most acetabular
      dysplasia in THA. In this way the anatomical rotational center can be obtained
      medially and lowly. The excellent long-term function will be maintained.

PMID- 15733452
TI  - [The methods of shorting of proximal femoral and total hip arthroplasty for old
      femoral neck fracture with severe hip joint dislocation].
AB  - OBJECTIVE: To discuss the effective method and outcome to old femoral neck
      fracture with severe hip joint dislocation. METHODS: From April 1996, 7 cases of
      old femoral neck fracture with severe hip joint dislocation were treated by the
      shorting of posterior femoral and total hip arthroplasty. RESULTS: The average
      age of 7 patients was 51 years old and the mean follow-up was 27.3 months. The
      mean Harris score was improved to 84.3 from 36.7 before operation in the latest
      follow-up. The prosthesis position of acetabular and femoral was excellent, there
      was no sinking or softening of artificial joint, nonunion of femoral osteotomy.
      CONCLUSION: The preliminary clinical results are quite satisfactory of the
      shorting of posterior femoral and total hip arthroplasty to old femoral neck
      fracture with severe hip joint dislocation, the follow-up is necessary for
      further long-term outcome.

PMID- 15733453
TI  - [Resection and reconstruction for primary pelvic tumors around acetabular].
AB  - OBJECTIVE: To discuss the resection of tumors, reconstruction of defects and the
      postoperative complications. METHODS: Thirty-one patients with tumors around
      acetabular were treated surgically in People's Hospital between July 1997 and
      July 2003. The series comprised 19 males and 12 females. Twelve patients were
      diagnosed with chondrosarcoma, 1 with Ewing sarcoma, 3 with osteosarcoma, 1 with
      lymphoma, 1 with carcinosarcoma, 1 with malignant fibrohistiocytoma (MFH), 2 with
      myeloma, 9 with giant cell tumor (GCT), 1 with aneurysmal bone cyst. Among 31
      patients with peri-acetabular tumors, 8 were reconstructed with hemi-pelvic
      prosthesis, 7 with saddle prosthesis, 6 with cauterized tumor bone and total hip
      arthroplasty, 10 with total hip replacement after curettage of lesion and
      cemented. RESULTS: Among 21 patients who underwent tumor resection and
      reconstruction in region II, 6 had local relapse. Two of 3 patients with
      osteosarcoma were dead. Five of 12 patients with chondrosarcoma were free of
      disease. Twenty-one patients with acetabular reconstruction after resection of
      lesions in region II could sit and stand normally and walked with a cane, several
      of which even had normal gait. CONCLUSION: Allograft or pelvic prosthesis can be
      used to reconstruct the acetabulum after resection of tumors. We must pay more
      attention on the following points in the surgical treatment of periacetabular
      tumors: (1) Extensively resect tumors as far as possible; (2) Be acquainted with
      advantages and disadvantages of different reconstructive methods of acetabulum to
      prevent the complications; (3) The reconstructed acetabulum is unstable, so the
      patients must stand with a cane to protect the reconstructed hip joint; (4)
      Prevent wound necrosis and infection; (5) Surgical treatment of pelvic tumors
      would easily result in poor wound healing especially in the patients receiving
      chemotherapy or radiotherapy because of extensive soft tissue stripping. The
      destroyed soft tissue caused by chemotherapy or radiotherapy may increase the
      great tissue tension after implantation of allograft. And the factors of poor
      blood supply and hematoma in the wound theoretically increase the chance of
      infection.

PMID- 15733454
TI  - [Clinical study on treatment of lumbar degenerative spondylolisthesis by using
      general spine system].
AB  - OBJECTIVE: To observe early clinical efficacy of general spine system (GSS) in
      spondylolisthesis combined with lumbar canal stenosis, lumbar decompression,
      reduction and bone graft. METHODS: Sixteen patients with degenerative lumbar
      spondylolisthesis combined with lumbar canal stenosis, 10 male, 6 female, average
      age 58.5 years (range 42 - 72 years) underwent lumbar decompression, bone graft
      and internal fixation using GSS. Preoperatively 10 patients had degree I
      spondylolisthesis and 6 patients had degree II spondylolisthesis. Clinical
      efficacy, reduction effectiveness and complications were recorded. RESULTS: The
      16 patients in this group were followed up postoperatively for an average of 21.2
      months (18 - 24 months). At latest follow-up after surgery, preoperative clinical
      symptoms had disappeared completely in 15 of 16 patients, and low back pain
      relief was seen in 15 patients. Average duration of surgery was 170 min (120 -
      270 min), and average blood loss was 375 ml (100 - 800 ml). X-ray results showed
      complete reduction for all spondylolisthesis patients, and results remained good
      in follow-up. Dura mater tearing, pedical fracture, nerve injury and other
      surgical complication did not occur. Screw breakage, screw loosening and
      instrument loosening at the screw-rod juncture were not observed after surgery or
      in follow-up. CONCLUSION: GSS provides good reduction for spondylolisthesis, and
      shows good early clinical efficacy.

PMID- 15733455
TI  - [Effect of pedicle screw fixation with bone cement in lumbar].
AB  - OBJECTIVE: To evaluate the strength of pedicle screw fixation with bone cement in
      human cadaveric lumbar vertebral bodies by using biomechanical test. METHODS:
      Twenty-four fresh frozen cadaveric lumbar vertebral bodies were randomly divided
      into 3 groups, which each group had 8 bodies. The bodies in the first group were
      drilled only. The bodies in the second group were drilled with tap. The bodies in
      the third group were drilled and the holes were enlarged by borer. Each vertebral
      body was drilled in both right and left sides, which one side served as control
      with the pedicle screws fixation only and another side served as testing side
      with the pedicle screw fixation with bone cement. The pullout strength was tested
      on both sides by using borer. RESULT: There was significant difference of
      manifestation of pull-strength between the control side and the testing side in
      all groups (P < 0.001). For the manifestation of pull-strength of testing side in
      different groups, which had pedicle screw fixation with bone cement, there was no
      significant difference between the second group and third group, however, the
      difference between the first group and the second group and between the first
      group and third group were significant. CONCLUSION: The pedicle screws with bone
      cements could significantly enhance the strength of fixation in cadaveric lumbar
      compared with pedicle screws only.

PMID- 15733456
TI  - [Perioperative management of orthopaedic patients with hemophilia A].
AB  - OBJECTIVE: To discuss the perioperative management of hemophiliacs A with
      orthopaedic complications. METHODS: To regulate the injection of factor VIII
      concentrate in peroperative period by testing the level of factor VIII:C in 27
      cases. The lever of factor VIII:C was improved to 30% - 50% at the day before the
      operation. To the severe patients, it was maintained at 58.5% - 89.3% during the
      operation and at 47.0% - 78.4% in postoperation. While to the gentle, it was
      maintained at 38.5% - 52.5% during the operation and at 29.2% - 52.3% in
      postoperation. The individualized surgical procedures were carried out, such as
      arthrocentesis, open knee synovectomy or arthroscopic synovectomy, evacuation or
      curettage of haematoma, debridements, internal fixation. RESULTS: All patients
      were cured in 14 - 105 days by regulating the injection of factor VIII during the
      peroperative period. The usage of factor VIII was 1 200 - 70 250 IU. CONCLUSION:
      While the hemophiliacs have orthopaedic complications, it is necessary to promise
      the factor VIII:C being maintained at the lever of hemostasis during the
      peroperative period. The hemophiliacs are endurable to the operation.

PMID- 15733457
TI  - [An experimental study of cell apoptosis and correlative gene expression after
      tractive spinal cord injury in rats].
AB  - OBJECTIVE: To observe the cell apoptosis after tractive spinal cord injury in
      rats, determine expression of apoptosis correlative genes, and study the
      molecular mechanism of cell apoptosis. METHODS: The T(13)-L(2) spinal cord of
      rats was injured by traction after the amplitude of P1-N1 wave decreased to 70%
      in postoperation than in preoperation through cortical somatosensory evoked
      potential (CSEP) monitor. Then rats were killed in 30 min, 6 h, 1, 4, 7, 14 and
      21 d respectively after operation (n = 4). Cell apoptosis was examined by the
      flow cytometer and terminal deoxynucleotidyl transferase-mediated DUTP-biotin
      nick end labeling (TUNEL) reaction, the expression of p53, bax and bc1-2 genes
      was tested with immunohistochemistry. RESULTS: The flow cytometer test and TUNEL
      method showed that the apoptosis cell ratio raised in 6 h and reached at peak in
      7 d after injury, and then declined till 21 d, they showed significant difference
      (P < 0.05, 0.01). TUNEL method showed that injured group had a large number of
      apoptosis glial cells in white matter. Immunohistochemical staining showed that
      the positive expression of p53, bax and bc1-2 protein raised at 6 h, expression
      of p53 protein reached at peak in 4 d, bax and bc1-2 protein reached at peak in 7
      d after injury. Compared with control group and laminectomy group, the injured
      group showed significant difference (P < 0.05, 0.01). CONCLUSION: There is cell
      apoptosis phenomenon after tractive spinal cord injury in rats. Morphology
      indicates that apoptosis includes neurons and glialcytes, which is an important
      form of cell death and pathological changes in secondary lesion period after
      tractive spinal cord. There exist high expression of apoptosis correlative gene
      p53 and bax after spinal cord injury, they may play an important role in
      reduction of cells to apoptosis.

PMID- 15733461
TI  - [Adrenal myelolipoma:clinical diagnosis and management of 26 cases].
AB  - OBJECTIVE: To evaluate the diagnosis and management of adrenal myelolipoma.
      METHODS: The clinical data of 26 cases were analyzed retrospectively and the
      selected articles were reviewed. There were no specific clinical symptom and
      endocrine abnormality, except increasing catecholamine in 2 cases. All cases but
      two were diagnosed by B-model ultrasound scanning (B-US), CT or magnetic
      resonance imaging (MRI). RESULTS: Twenty-six cases were surgically treated, the
      diameter of the tumor was 5 - 10 cm, simple tumor resection was performed in 16
      cases, and complete adrenal resection was performed in 10 cases. All the operated
      cases were proved by pathologists. The duration of follow-up was from 6 - 28
      months after surgery. No recurrence was observed. CONCLUSIONS: The diagnosis of
      adrenal myelolipoma could be established based on B-US, CT or MRI. The tumors
      whose diameter is larger than 5 cm in size should be removed.

PMID- 15733462
TI  - [Clinical analysis of 174 cases of primary ureteral carcinoma].
AB  - OBJECTIVE: To analyse the clinicopathological features and discuss the diagnosis,
      therapy and prognosis of primary ureteral carcinoma. METHODS: One hundred and
      seventy four cases of primary ureteral carcinoma diagnosed pathologically between
      January 1971 and July 2002 in our institution were followed up and
      retrospectively studied. RESULTS: The incidence of primary ureteral carcinoma was
      increasing during the last 30 years. The mean age of occurrence was 63.7 years.
      The most useful methods of detecting tumors preoperatively were retrograde
      urogram, CT, magnetic resonance urography and ureteroscopy, with positive
      percentage of 87.8% (86/98), 96.0% (48/50), 95.8% (23/24), 87.0% (20/23)
      respectively. 131 (75.3%) cases underwent nephroureterectomy with a cuff of
      bladder. 171 (98.3%) cases were transitional cell carcinoma. T(a-2) and G(1, 2)
      tumors account for 70% of all respectively. The 5 year and 10 year survival rates
      were 53.1% (52/98) and 30.5% (18/59) respectively. The subsequent bladder cancer
      occurred in 38 cases (23.8%), and the subsequent contralateral ureteral carcinoma
      occurred in 6 cases (3.8%). CONCLUSIONS: The prognosis of primary ureteral
      carcinoma is poor. Tumor stage and grade are both the prognostic factors. Precise
      preoperative diagnosis and more effective adjuvant therapy may improve the
      prognosis.

PMID- 15733463
TI  - [The combined therapy of intervention, operation and biology in patients with
      middle-advanced renal cell carcinoma].
AB  - OBJECTIVE: To observe the effect of the combined therapy of intervention,
      operation and biology in patients with middle-advanced renal cell carcinoma.
      METHODS: Combined therapy was used in 52 cases as combined care groups and the
      single operational therapy was used in 50 cases as control group. Compare their
      resection rates, surgical risks and 3, 5 years survival rates. RESULTS: In the
      combined care group, the excision rate was 100%, the average amount of blood
      transfusion during the operation was 280 ml, the average operation time was 100
      minutes, and the 3, 5 years survival rates were 73% and 50%; While in the control
      group, the results were 90%, 396 ml, 130 minutes, 55% and 27% respectively. There
      were significant differences between 2 groups (P < 0.05). CONCLUSION: Combined
      therapy could elevate resection rates and 3, 5 years survival rates and decrease
      surgical risks.

PMID- 15733464
TI  - [The influence of neuroendocrine differentiation on the growth and androgen
      receptor expression of prostate carcinoma cells].
AB  - OBJECTIVE: To study the paracrine effect of the neuroendocrine differentiation
      cells and its influence on androgen receptor expression of prostate carcinoma
      cells. METHODS: Established an in vitro induced model of neuroendocrine
      differentiation of prostate carcinoma (LNCaP(NE), PC-3M(NE)), and investigate the
      proliferation effect of neuroendocrine phenotype cells (LNCaP(NE), PC-3M(NE)) on
      other non-neuroendocrine phenotype cells (LNCaP, PC-3M) by feeding non
      neuroendocrine phenotype cells with the medium pre-incubated with induced
      neuroendocrine phenotype cells. It was also tested the regulation of androgen
      receptor mRNA and androgen receptor protein expression of LNCaP(NE) cells on
      LNCaP cells by reverse transcriptase polymerase chain reaction and Western Blot
      in the presence or absence of androgens. RESULTS: The medium pre-incubated with
      PC-3M(NE) cells could promote the proliferation of PC-3M cells. The medium pre
      incubated with LNCaP(NE) cells could promote the proliferation of LNCaP cells,
      and reduce the expression of androgen receptor in the latter in the absence of
      androgens, but the negative results were observed in the presence of androgens.
      CONCLUSIONS: The neuroendocrine phenotype cells of prostate cancer can reduce the
      expression of androgen receptor in prostate cancer cells and promote them to
      proliferate by means of paracrine in the blockade of androgens.

PMID- 15733465
TI  - [Inhibitory effect of recombinant transforming growth factor alpha-pseudomonas
      exotoxin 40 on human bladder cancer cell proliferation].
AB  - OBJECTIVE: To study inhibitory effect of recombinant transforming growth factor
      alpha-Pseudomonas exotoxin fusion protein (TP40) on proliferation of the human
      bladder cancer T24 cells. METHODS: Expression of epidermal growth factor receptor
      (EGFR) in cultured T24 cells was analyzed with Western blot assay. Human bladder
      cancer T24 cells were exposed to TP40 at 5 - 1 000 microg/L. Methyl thiazolyl
      tetrazolium assay was applied to evaluate the cell proliferation by measuring the
      absorbance (A) at 570 nm with a microplate reader. Tritium labeled thymine
      deoxyriboside ([(3)H]-TdR) uptake was measured to observe DNA synthesis.
      Competition assays were performed by the EGF at 1 - 7 500 microg/L. RESULTS:
      Expression of EGFR was high in human bladder cancer T24 cells. Cell growth was
      suppressed by 10%, 19%, 27%, 41%, 47%, 53% and 61% after 96 h treatment with TP40
      at 5, 50, 100, 250, 500, 750 and 1 000 microg/L, respectively. [(3)H]-TdR
      incorporation was 80%, 69%, 48% and 51% after 24 h, 48 h, 72 h, 96 h treatment
      with TP40 at 750 microg/L, respectively. When the concentration was 1 - 7 500
      microg/L, EGF could block the inhibitory effect of TP40 to some extent.
      CONCLUSIONS: Human bladder cancer T24 cells express EGFR at a high level. TP40
      could inhibit the growth of T24 cells effectively in a dose- and time-dependent
      manner. The cytotoxic effects of TP40 were specifically mediated by EGFR.

PMID- 15733475
TI  - [Reconstruction of periprosthetic fractures of hip with cortical bone plates
      allografts].
AB  - OBJECTIVE: To observe clinical results for reconstruction of periprosthetic
      fractures of hip with cortical bone plates allografts by deep-freezing and
      ethylene oxide treatment. METHODS: Seven patients with periprosthetic fractures
      of hip underwent cortical bone plates allografts by deep-freezing at -70 degrees
      C after being treatment of 48 degrees C ethylene oxide. And evaluate clinical
      outcome by examining T lymphocytes, Harris scores, X-rays photograph, and bone
      scintigraphy. RESULTS: There were not activity of immune rejection and infection
      in all patients. Harris scores of patients increased 21, 32, 40, 40 scores at 3,
      6, 12, 24 months after surgery. T-lymphocytes, antibody and immunocomplex in
      blood was normal postoperation. X-ray film indicated that fracture was healed at
      3 months and there was partially bone conjunction between allograft strut and
      host bone. There was incorporation of 85% allograft strut to host bone, and 15%
      allograft strut was partially absorbed at 12 months after surgery. The size of
      femur of host was added 3 mm to 5 mm, averaged 4.3 mm at 12 months postoperation.
      Density of 80% allograft plates was as same as host bone after remodeling and the
      absorbtion of 10% allograft plates stopped at 24 months after surgery. There was
      thick of nuclein in the area of allograft cortical bone plates by bone
      scintigraphy examination at 3 months postoperation, and the thick of nuclein was
      stronger at 6, and 12 months after surgery. CONCLUSION: Allograft cortical bone
      plates by deep frozen at -70 degrees C after being treatment of 48 degrees C
      ethylene oxide is suitable for mechanical fixation and biological bone
      transplantation, and it can increase bone reservation, augment strength of femur
      once the allograft strut incorporates to host bone, and avoid removing metal
      implant in second operation when being applied into reconstruction femoral
      fracture in joint replacement.

PMID- 15733476
TI  - [Transtrochateric rotational osteotomy for osteonecrosis of the femoral head].
AB  - OBJECTIVE: To explore the indications, operative technique and clinical results
      of the transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the
      femoral head (ONFH). METHODS: Nineteen patients (23 hips) with ONFH underwent TRO
      from October 1992 to May 2001 were reviewed. There were 14 males and 5 females.
      The age was ranging from 22 to 43 years old with an average age of 33.4 years
      old. The etiology were as followed: alcoholism 10 cases (12 hips); steroid 6
      cases (7 hips); trauma 2 cases (2 hips); caisson disease 1 case (2 hips). Ficat
      stage: II 8 cases 8 hips; III 11 cases 15 hips. Harris hip score 46 to 74 with
      mean score 56 preoperatively. In order to determine the location and extent of
      osteonecrosis, A-P view and accurate lateral view (the film should be placed
      parallel to the femoral neck with the hip in precisely 90 degrees and flexion 45
      degrees of abduction and neutral rotation) were taken in both hips
      preoperatively. The surgical technique described by Sugioka were used in all
      patients. RESULTS: Seventeen patients (19 hips) were followed up ranging from 18
      to 11 years with mean 54 months. The Harris hip score was from 55 to 94 with mean
      80.5. Fourteen hips score more than 80 and good to excellent rate was 73.2%.
      Harris score were less than 79 in 5 cases and 4 hips of these 5 hips were revised
      by total hip arthroplasty. The rotation angle was from 55 degrees to 80 degrees
      with mean 60 degrees . COMPLICATIONS: The circumflex femoral medial artery injury
      was found in 1 hip; subtrochanteric fracture was found in 2 hips and 1 osteotomy
      site nonunion occurred. CONCLUSION: TRO can be used to treat ONFH. The
      indications include: (1) younger patients (less than 45 years old). (2) Ficat
      stage II and III with more than one third intact articular surface of the femoral
      head. The better results could be obtained using posterior rotation and lager
      rotational angle. The Sugioka osteotomy should be used carefully because of its
      complicated surgical technique.

PMID- 15733477
TI  - [Evaluation of neck moving ability after anterior cervical fusion].
AB  - OBJECTIVE: To observe the relationship of adjacent segment degeneration and neck
      symptom after anterior cervical fusion. METHODS: Making follow-up to 66 cases who
      had accepted anterior cervical fusion for 1 - 16 years, average 10.5 years.
      Observe the mobilization and gliding degree of adjacent segment in flexion
      extension X-ray film, neck symptom, and the relationship of them. In 59 of these
      patients, the mobilization of entire cervical spine and non-fusion segment was
      observed before/after operation. RESULTS: The incidence of adjacent segment
      instability in follow-up term was 72.7%, and 40.9% of all patients had
      significant neck symptom. The rate of significant neck symptom in patients who
      had instability was 48%, whereas which in patients without instability was 18.8%,
      and the difference was statistically significant (P < 0.05). The difference of
      mild instability and severe instability was not statistically significant (P >
      0.1). The mobilization of entire cervical spine decreased obviously (P < 0.001).
      The mobilization of adjacent segment increased obviously (P < 0.01), and which of
      non-adjacent segment had no change (P > 0.05). CONCLUSION: Majority of patients
      who have accepted anterior cervical fusion possessed instability of adjacent
      segment, but many of them have no symptoms. Adjacent segment instability is one
      of the reasons that induce neck symptoms.

PMID- 15733478
TI  - [Comparative study of vertebral body stress distribution following insertion of
      artificial lumbar intervertebral disc].
AB  - OBJECTIVE: To study vertebral body stress distribution of normal disc, post
      Diskectomy and artificial disk respectively by 3-D finite element methods, and to
      explore artificial intervertebral disk insertion impact on stress distribution of
      vertebral body. METHODS: Models of normal disk, post-Diskectomy, artificial disk
      and L(4 - 5) motion segment were established by using finite element software
      MSC. MARK, then vertebral body stress was analyzed through model of L(4 - 5)
      motion segment respectively. RESULTS: The vertebral body's stress was the
      smallest after insertion of artificial intervertebral disk (AID), and its stress
      distributed equally. But the stress under post-discectomy was bigger than the
      normal disc's in all the motion state. On the other hand, the stress distribution
      state of the post-discectomy changed while the spine were in different motion
      state, during the spine flexion, the stress in the anterior of vertebral body was
      the biggest; While extension, in the posterior and in right flexion state, the
      biggest stress was in the right. While vertical compression and rotation, the
      stress distributed equally. CONCLUSION: The results illustrate that the vertebral
      body's stress is the smallest after insertion of AID in 3 groups of all motion
      state, and its stress distributes equally. But the level of vertebral body stress
      increases after discectomy comparing with the normal group. In generally, it is
      much more reasonable that the disc is reconstructed with AID because of the
      biomechanical effect on vertebral body made by AID insertion.

PMID- 15733479
TI  - [The effect of intraoperative continuous nimodipine infusion on cerebral
      vasospasm during intracranial aneurysm surgery].
AB  - OBJECTIVE: To evaluate the effect of intraoperative continuous nimodipine
      infusion on cerebral vasospasm during intracranial aneurysm surgery. METHODS:
      Thirty consecutive patients under-going intracranial aneurysmal surgery were
      prospectively randomized into two groups: Isoflurane (group A, n = 15) and
      nimodipine (group B, n = 15). The patients in group A were maintained with 1
      minimum alveolar concentration (MAC) isoflurane anesthesia during the whole
      procedure. The patients in group B were given nimodipine infusion continuously
      (20 microg.kg(-1).h(-1)) after induction of anesthesia and anesthetized with 1
      MAC isoflurane. S100B levels in cerebrospinal fluid were determined before
      aneurysm clipping and 0, 2, 4 h after aneurysm clipping by enzyme linked
      immunosorbent assay. Assessment of mean blood flow velocity of parent arterial
      and arterial branches were performed before and after aneurysm clipping. RESULTS:
      (1) S100B in cerebrospinal fluid was increased significantly at 4 h after
      aneurysm was clipped in group A (F = 4.11, P < 0.05). However, S100B in
      cerebrospinal fluid was stable in group B in the whole procedure. (2) Mean
      arterial flow velocity of parent vessels in group B was lower significantly than
      that in group A (t = 2.08, P < 0.05). However, mean arterial flow velocity of
      distal vessels in both groups has no significant difference. CONCLUSION:
      Intraoperative nimodipine infusion may prevent cerebral vasospasm during
      intracranial aneurysm surgery.

PMID- 15733480
TI  - [Association of polymorphisms in testosterone 5-alpha-reductase II genotype and
      prognosis factors of prostate cancer].
AB  - OBJECTIVE: The correlation were studied between testosterone 5-alpha-reductase II
      (SRD5A2) gene polymorphisms and prognosis factors. METHODS: V89L and A49T
      variants was identified with Mwo1 and Rsa1. The differences of V89L and A49T
      between cancer of prostate (CaP) and benign prostatic hyperplasia (BPH) were
      studied. In addition, we also researched the association of polymorphisms with
      age of onset, free prostate specific antigen (FPSA), total PSA (TPSA), FPSA/TPSA
      (F/T), Gleason score, and T stage in cancer group. RESULTS: We found no
      differences of V89L and A49T polymorphisms between CaP and BPH. In CaP group the
      A49T variant was associated with lower age of onset (P = 0.03) and higher Gleason
      score (P = 0.015). There were no differences between VV and VL+LL polymorphisms
      with any of the characteristics studied. When the characteristics above were
      regarded as two-level discrete variable, there were no differences by A49T and
      V89Lvariants. CONCLUSION: In CaP group, the AT+TT genotype was perhaps associated
      with poor prognosis. VL+LL genotype has no relation with prognosis.

PMID- 15733481
TI  - [Experimental study on the prevention of epidural scar adhesion with
      polycaprolactone/polylactic acid membrane].
AB  - OBJECTIVE: To evaluate the ability of a polycaprolactone/polylactic acid
      (PCL/PLA) membrane to inhibit epidural scar adhesion after laminectomy, and
      observe the responsive changes of the pain media in the spinal cord. METHODS:
      L(1), L(3) laminectomies were performed on 96 Wistar rats. The rats were divided
      into 3 groups: None-implant Control Group (NC), Autologous free fat graft group
      (AFFG) and PCL/PLA membrane group (PCL/PLAm). The rats were killed at 1, 3, 6,
      and 12 weeks postoperatively. Epidural scar formation and adhesion were observed
      grossly and histologically. Reverse transcription polymerase chain reaction (RT
      PCR) were used to analyses the expression of Transforming growth factor beta (TGF
      beta) in the epidural scar. Immunohistochemistry stain and RT-PCR were performed
      to evaluate the expression of the substance P and the c-fos gene in the relevant
      spinal cord, and the results were analyzed statistically. RESULTS: Gross
      evaluation and histological evaluation showed that in the NC lamina defect site
      had much scar tissue and had wide and tight adhesions to the dura; in the AFFG,
      with the fat degrading gradually, the adhesions were increased; whereas in the
      PCL/PLAm group, there were slightly adhesions to the dura. RT-PCR showed that the
      expression of the TGF-beta was much less in the PCL/PLAm group than in the NC
      group. The insertion of the PCL/PLA membrane and the fat patch reduced the
      expression of the substance P and the c-fos gene in the spinal cord. CONCLUSION:
      The insertion of the PCL/PLA membrane reduces scar formation and separates
      fibrosis tissue from the dura, the results indicate that PCL/PLA membrane is an
      effective way of reducing peridural scar formation and preventing the failed back
      surgery syndrome.

PMID- 15733482
TI  - [The study of the pro-nucleating activity of bacteria identified in cholesterol
      gallstones in model bile systems].
AB  - OBJECTIVE: To explore the relationship of bacteria identified in cholesterol
      gallstones and gallstone formation. METHODS: Observe the bacteria activity in
      model bile and the influence of bacteria on the cholesterol nucleation time (NT).
      RESULTS: (1) Model bile were suitable for the growth of E. coli, Pseudomonas
      aeruginosa, staphylococcus aureus, enterococcus faecalis, clostridium difficile
      and Clostridium. Propionibacterium acne grew weakly and the growth of Bacteroides
      fragilis was restrained in model bile. (2) Only pseudomonas aeruginosa and
      enTerococcus faecalis could ly shorten the cholesterol nucleation time. (3) With
      pseudomonas aeruginosa or enTerococcus faecalis added in model bile, the
      formation of cholesterol crystals presented a progressive course of evolution.
      CONCLUSIONS: Pseudomonas aeruginosa and enterococcus faecalis, not
      propionibacterium acne, have pro-nucleating ability in model bile.

PMID- 15733483
TI  - [The significance of pepsinogen with its subgroup and CA72-4 associate detect
      applied to early diagnostic and prognosis judgment on gastric cancer].
AB  - OBJECTIVE: To find out the connection of serum pepsinogen and it's subgroups
      (PGI, PGII) with CA72-4 to early diagnosis and postoperative recurrence on
      gastric cancer. METHODS: RIA was applied to detect the results of serum PGI, PGII
      and CA72-4 on gastric cancer and other stomach diseases, then the clinic value of
      associating detection on gastric cancer diagnosis and prognosis judgment were
      assessed. RESULTS: The serum PG levels of GC patients were significantly lower
      comparing to those of healthy controls (P < 0.01), apparent changes had taken
      place on earlier period GC (P < 0.05), and aggressive GC were even lower (P <
      0.01). On the earlier period of GC diagnosis, CA72-4 levels were not apparently
      different to healthy controls (P > 0.05), and aggressive GC were significantly
      higher (P < 0.01). Compared preoperative with postoperative, the serum PGI and
      PGII and CA72-4 levels were significantly different (P < 0.01). In the patients
      underwent total gastrectomy, both of pepsinogen levels were lower than those of
      subtotal or large partial gastrectomy (P < 0.05). The serum PGI, PGII and CA72-4
      levels of patients with recurrence of GC after total gastrectomy were
      significantly higher than those without. Compared before recurrence patients with
      after ones, the serum PGI and PGII levels of partial gastrectomy were no apparent
      difference (P > 0.05), however apparent changes had taken place on CA72-4 levels.
      The associate detection had even higher specificity (P < 0.01). CONCLUSIONS:
      Apply to detect the serum PG levels on crowds, especially pGI, PGI/II levels
      decrease, which may be expected to become the index to earlier period GC
      screening. The associating detection to PG and CA72-4 levels may significantly
      improve sensitivity and specificity, which have chances to be applied to
      monitoring to postoperative gastrectomy.

PMID- 15733485
TI  - [The expression and significance of hypoxia-inducible factor-1 alpha and related
      genes in abdominal aorta aneurysm].
AB  - OBJECTIVE: To study the expression of hypoxia-inducible factor (HIF)-1alpha and
      related genes in abdominal aorta aneurysm (AAA) and explore the underlying
      pathogenesis. METHODS: Twenty-two AAA specimens were collected and 5 normal
      abdominal aorta tissue were used as control. Northern blot, western blot and
      immunohistochemistry were used to evaluated the expression of HIF-1alpha mRNA and
      protein product. Western blot and immunohistochemistry method were also used to
      determine the expression of vascular endothelial growth factor (VEGF) and caspase
      3. Microvessel density (MVD) was studied by immunohistochemistry stain of CD34.
      RESULTS: The expression of HIF-1alpha mRNA and protein product were significantly
      higher in AAA than that in normal abdominal aorta (P < 0.01). The expression of
      VEGF and caspase-3 were also higher in AAA and both had a significantly positive
      relationship with HIF-1alpha expression (P < 0.01). Most of the positive cells
      located in VSMC and adventitia of AAA. The MVD counts were higher in AAA.
      CONCLUSION: HIF-1alpha may have an important role the development of AAA, which
      maybe obtained by regulating the expression of VEGF or caspase-3.

PMID- 15733486
TI  - [Laser inducing mucosal fibrosis for preventing recurrence of esophageal
      varices].
AB  - OBJECTIVE: To investigate the prevention of esophageal varices recurrence by
      laser inducing esophageal mucosal fibrosis. METHODS: Our study included 42
      patients after esophageal varices eradicated by endoscopic varices ligation, and
      they were divided into 2 groups randomly, each group included 21 patients. One
      group was assigned to received laser treatment, and indocyanine green solution (1
      mg/ml) was injected submucosally, a diode laser (power 10 watts) was applied to
      the surface from the esophagogastric junction to 5 cm above it. Another group was
      controlling without any treatments. All patient were followed up by endoscopy
      every 3 months until 12 months. RESULTS: Laser irradiation was performed safely
      without any major complications. And lower esophageal mucosa produced fibrosis
      widely after laser irradiated 1 month. After 12 months follow up, the cumulative
      recurrence rate was significantly lower than the control group, 14% (3/21) vs 43%
      (9/21) (chi(2) = 4.20, P < 0.05). CONCLUSIONS: Our study indicates that laser
      inducing mucous fibrosis is safely and can prevent recurrence of esophageal
      varices.

PMID- 15733498
TI  - Antibiotics for upper respiratory tract infections: an overview of Cochrane
      reviews.
AB  - OBJECTIVES: The aim of this paper is to review the four Cochrane reviews of
      antibiotics for upper respiratory tract infections. METHODS: Each Cochrane review
      was read and summarized, and results presented as odds ratios (as in the Internet
      version) and, where relevant, numbers needed to treat. RESULTS: The reviews of
      antibiotics for acute otitis media have concluded that benefit is not great with
      a number needed to treat for a benefit (NNTB) of 15. Recent US guidelines are
      recommending a delay in prescriptions in children over the age of 6 months. For
      streptococcal tonsillitis, the Cochrane reviewers suggest that antibiotic use
      seems to be discretionary rather than prohibited or mandatory. This is because
      the benefit in terms of symptoms is only about 16h (NNTB from 2 to 7 at day 3 for
      pain) compared with placebo, and that serious complications, such as rheumatic
      fever and glomerulonephritis, are now rare in developed countries. The reviewers
      do, however, suggest that antibiotics are considered in populations in whom these
      complications are more common. This is an area of debate, as the Infectious
      Disease Society of America (2002) recommends routine treatment. [Clin. Infect.
      Dis. 35 (2002) 113] There is good evidence and consensus that there is no
      indication for antibiotics for the common cold. The situation with acute purulent
      rhinitis is less clear, as new evidence suggests that antibiotics may be
      effective for acute purulent rhinitis (NNTB from 6 to 8). However, as most people
      with acute purulent rhinitis improve without antibiotics, giving antibiotics is
      not justified as an initial treatment. For acute maxillary sinusitis, the
      evidence suggests that antibiotics are effective for people with radiologically
      confirmed sinusitis. The reviewers suggest that clinicians should weigh up the
      modest benefits (NNTB from 3 to 6) against the potential for adverse effects.
      CONCLUSION: The use of antibiotics for acute otitis media, sore throat and
      streptococcal tonsillitis, common cold and acute purulent rhinitis, and acute
      maxillary sinusitis seems to be discretionary rather than prohibited or
      mandatory, at least for non-severe cases.

PMID- 15733499
TI  - Resistant hepatic hydrothorax: a successful case with treatment by nCPAP.
AB  - Hepatic hydrothorax is defined as pleural effusion with liver cirrhosis but no
      primary cardiopulmonary disease. Hepatic hydrothorax is often resistant to
      various therapeutic interventions. The most likely cause is the transfer of
      ascites fluid from the abdomen to the pleural space via the diaphragm because of
      a negative intrathoracic pressure gradient. A 62-year-old man was diagnosed with
      hepatoma and cirrhosis. After a partial hepatectomy, he suffered with hepatic
      hydrothorax. He had snoring without obvious sleep apnea. The patient's hepatic
      hydrothorax markedly improved following nasal continuous positive airway pressure
      (nCPAP) treatment during sleep. The mechanism for the improvement may have been
      the intrathoracic positive pressure during sleep induced by the nCPAP treatment
      during sleep. nCPAP treatment may provide a new therapy for resistant hepatic
      hydrothorax.

PMID- 15733500
TI  - The polymorphism C5507G of complement receptor 1 does not explain idiopathic
      pulmonary fibrosis among the Finns.
AB  - Idiopathic pulmonary fibrosis is the most common of the idiopathic interstitial
      lung diseases referring to the histo-pathological entity of usual interstitial
      pneumonia. It has been hypothesized that inflammation may trigger the multiformic
      fibrotic lesions found in the affected lung, and defects in the innate immune
      defense, including the complement, can predispose to pulmonary fibrosis. The
      polymorphism C5507G in the Complement Receptor 1 gene has been recently
      associated with idiopathic pulmonary fibrosis. C5507G causes an amino acid change
      from proline to arginine, and opens a potential cleavage site for trypsin-like
      enzymes and, therefore, a potential mechanism for increased shedding of the
      molecule from the cell surface. We studied the polymorphism in 96 Finnish
      patients with idiopathic pulmonary fibrosis and 164 population based controls.
      All the patients and controls were C5507 homozygous suggesting that either the
      Finns do not carry the G5507 polymorphism or it is extremely rare. We conclude
      that G5507 is not a susceptibility allele for idiopathic pulmonary fibrosis among
      Finnish patients.

PMID- 15733501
TI  - Management of community-acquired pneumonia and secular trends at different
      hospitals.
AB  - STUDY OBJECTIVES: The goal of this study was to assess variability in the
      management of patients admitted to hospitals with community-acquired pneumonia
      (CAP), and changes in secular trends of this condition. METHODS: Observational
      study carried out, in 5 teaching hospitals, in northern Spain of patients
      admitted with CAP between March 1,1998 and March 1,1999 (baseline period), and
      between March 1, 2000 and September 30, 2001 (follow-up period). Clinical
      histories were analyzed retrospectively for relevant parameters for process-of
      care and outcome performance. Those parameters among hospitals during the
      baseline period were compared. For each hospital, changes in these parameters
      between baseline and follow-up were also measured. All parameters were adjusted
      for disease severity. RESULTS: A total of 844 patients were included in the
      baseline period, and 654 in the follow-up period. During the baseline period,
      adjusted analyses revealed statistically significant differences in all process
      of-care parameters except the coverage of atypical pathogens. With regard to
      clinical outcomes, however, only the 30-day readmission rate was significantly
      different (P=0.03). Adjusted mean length of stay ranged from 6.3 to 9.2 days
      (P<0.0001). In adjusted analyses of temporal changes within hospitals for process
      of-care and outcome performance, revealed few statistically significant
      differences. CONCLUSIONS: Variability discovered between hospitals in the
      management of patients in the absence of relevant secular changes in each
      hospital points out the necessity to implement measures designed to reduce such
      variability between hospitals and to improve the quality of medical treatment.

PMID- 15733502
TI  - Helicobacter pylori seroprevalence in patients with chronic obstructive pulmonary
      disease.
AB  - An increased seroprevalence of Helicobacter pylori (H. pylori) and especially of
      the high virulent cytotoxin-associated gene-A (CagA) positive strains has been
      found in several extragastroduodenal pathologies, characterized by activation of
      inflammatory mediators. Moreover, it has been reported that the risk of chronic
      bronchitis may be increased in H. pylori infected patients. The aim of the
      present study was to assess the seroprevalence of H. pylori and in particular of
      CagA-positive virulent strains in patients with chronic obstructive pulmonary
      disease (COPD). We evaluated 126 COPD patients (88 males and 38 females, aged
      61.3+/-8.1 years) and 126, age and sex-matched, control subjects. All subjects
      enrolled underwent an enzyme-linked immunosorbent assay (ELISA) IgG serologic
      test for H. pylori and CagA protein. The prevalence of H. pylori infection in
      patients and controls was 77.8% and 54.7%, respectively (P<0.001) and that of
      CagA-positive H. pylori infection was 53.9% and 29.3%, respectively (P<0.001).
      Moreover, COPD patients had a significantly increased mean serum concentration of
      both anti-H. pylori IgG (118.3+/-24.4 vs. 61.9+/-12.9U/ml, P<0.001) and anti-CagA
      IgG antibodies (33.8+/-3.4 vs. 19.0+/-1.5U/ml, P<0.001). Finally, no
      statistically significant difference, as regards the spirometric values, was
      detected between H. pylori infected COPD patients and uninfected ones. In
      conclusion, H. pylori infection may be associated with COPD. Further studies
      should be undertaken to clarify the potential underlying pathogenetic mechanisms.

PMID- 15733503
TI  - Fluoroscopy-guided barium marking for localizing small pulmonary lesions before
      video-assisted thoracic surgery.
AB  - PURPOSE: To evaluate the effectiveness of fluoroscopy-guided barium marking for
      localization of small peripheral pulmonary lesions before video-assisted thoracic
      surgery (VATS) resection. MATERIAL & METHODS: Twenty-one patients with peripheral
      pulmonary lesions 15 mm or less in diameter who were scheduled to undergo VATS
      resection were studied. A catheter was inserted bronchoscopically into the target
      segment and guided to a presumed lesion. The tip of the catheter was confirmed
      fluoroscopically to be at the exact spot determined beforehand. A 50%
      (weight/volume) barium sulfate suspension was instilled into the bronchus through
      the catheter, and the site of barium marking was ascertained by CT scanning.
      RESULTS: The average instilled volume of barium was 0.42+/-0.07 ml. On CT scans,
      barium spots were superimposed on the target lesions in 19 of the 21 patients and
      were only 6-7 mm from the lesions in the other 2. Barium was well preserved in
      all patients at the time of VATS resection. A mild cough persisted for about 1
      week in one patient, but the other patients had no specific complications.
      CONCLUSION: Fluoroscopy-guided barium marking is a safe, convenient, and reliable
      method for localization of small pulmonary lesions before VATS resection.

PMID- 15733504
TI  - Ciliary central microtubular orientation is of no clinical significance in
      bronchiectasis.
AB  - It has been suggested that patients with bronchiectasis might have increased
      central microtubular orientation angle (CMOA), which leads to poor coordination
      of ciliary beating, and consequently impairment of airway defence. We have
      employed transmission electron microscopy to assess CMOA of ciliated nasal mucosa
      in a cohort of 133 (81F, 56.8+/-16.1yr) stable bronchiectasis and 59 healthy
      subjects (30F, 49.3+/-22.1yr). There was no significant difference in CMOA
      between bronchiectasis (13.2 degree) and control subjects (13.0 degree, P=0.82).
      There was no significant difference in CMOA among patients according to the
      etiology of bronchiectasis, presence of nasal symptoms, or sputum status of
      Pseudomonas aeruginosa infection. Patients with more severe bronchiectasis, i.e.
      those with FEV(1) <60%, FVC <60%, or more than 4 bronchiectatic lung lobes, had
      significantly lower CMOA than their counterparts (P<0.05). There was no
      correlation between CMOA with age, 24h sputum volume, exacerbation frequency,
      FEV(1), FVC, or the number of bronchiectatic lung lobes (P>0.05). CMOA correlated
      with ciliary beat frequency (negative), and the percent of cilia showing
      ultrastructural or microtubular defects (P<0.05). Central microtubular
      orientation angle does not correlate with clinically important parameters, in
      contrary to the results reported by previously published smaller scale studies.

PMID- 15733505
TI  - Gefitinib ("Iressa"): a new therapy for advanced non-small-cell lung cancer.
AB  - Patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis
      and suffer many disease-related symptoms. Treatments should therefore aim to
      palliate these symptoms as well as improve overall quality of life. Gefitinib
      ("Iressa") is a novel epidermal growth factor receptor tyrosine kinase inhibitor
      that targets cell signaling involved in tumor growth and differentiation. In
      Phase II trials in recurrent NSCLC, gefitinib provided objective responses and
      symptom relief, and was generally well tolerated. Now approved for the treatment
      of advanced NSCLC in over 25 countries, including Japan and the USA, gefitinib
      has demonstrated significant clinical benefit in a disease area with limited
      treatment options.

PMID- 15733506
TI  - Loss of heterozygosity (LOH) in non-small cell lung cancer: difference between
      adenocarcinoma and squamous cell carcinoma.
AB  - BACKGROUND: In non-small cell lung cancer, a loss of heterozygosity (LOH) is
      frequently observed; however, few studies have investigated the differences in
      the LOH status between adenocarcinoma and squamous cell carcinoma. PATIENTS AND
      METHODS: In a consecutive series of 49 patients with adenocarcinomas and 22
      patients with squamous cell carcinomas, the LOH in tumors was analyzed using
      polymerase chain reaction employing 5 fluorescence-labeled dinucleotide markers
      (D2S123, D5S107, D10S197, D11SS904, D13S175) and an autosequencer. RESULTS: LOH
      was more frequently observed in squamous cell carcinoma (20 of 22, 90%) than in
      adenocarcinomas (33 of 49, 67%) (P=0.0348), and the number of LOH per patient was
      also higher in the patients with squamous cell carcinoma (2.2+/-1.4) than in
      those with adenocarcinoma (1.5+/-1.2, P=0.037). In adenocarcinomas, the number of
      LOH per patients correlated significantly with the pack-year index, whereas the
      pathological stage significantly affected the number of LOH in squamous cell
      carcinomas. CONCLUSION: The presence of LOH is relatively uncommon in
      adenocarcinoma of the lung; however, the incidence of LOH tends to be associated
      with the smoking status.

PMID- 15733507
TI  - Role of different nocturnal monitorings in the evaluation of CPAP titration by
      autoCPAP devices.
AB  - The aim of the study was to assess how the analysis of different signals recorded
      during application of automatic continuous positive airway pressure (autoCPAP)
      devices improves the evaluation of pressure titration in patients with
      obstructive sleep apnea syndrome (OSAS) naive to treatment. Seventy-two patients
      underwent nocturnal polysomnography during autoCPAP (Autoset T, ResMed, Sydney,
      Australia) application. Progressively more complex combinations of signals were
      analysed in consecutive steps. According to the analysis of oxyhemoglobin
      saturation (SaO(2)) alone, a fixed CPAP level suitable for treatment could not be
      identified in 3 subjects. When analysis of posture was added, titration was
      considered unsatisfactory in 1 more subject, due to a short time spent supine.
      Further, addition of flow and respiratory movements led to consider titration
      unsatisfactory in 1 more subject. Analysis of all polysomnographic signals
      demonstrated a not fully reliable titration in 9 subjects: 1 with short sleep
      duration, 2 without REM sleep, 4 with a short sleep time spent supine, and 3
      subjects (already identified by SaO(2)) with insufficient correction of
      respiratory disorders even when a relatively high CPAP was administered. Mask
      leaks did not hamper titration. CPAP titration by automatic devices alone results
      in imperfect titration in >10% subjects naive to ventilatory treatment. Only
      polysomnographic recording ensures titration reliability in all patients. Further
      research is needed to identify simple and economic methods to reliably start the
      CPAP treatment.

PMID- 15733508
TI  - A randomized controlled study of a computerized limited education program among
      young adults with asthma.
AB  - The aim of the study was to assess the effectiveness of a computerized limited
      asthma education program, designed to suit young people. The study was conducted
      with 97 young adults (18-25 years) with asthma, 48 were randomized to the
      intervention group and 49 to the control group, and they were followed for 12
      months. The intervention group completed an interactive computer program of 30
      min duration providing information about asthma, mechanisms, trigger factors,
      allergies and medication use, which was followed by a 30-min discussion with a
      specialized asthma nurse. The control group followed the routine schedule for
      asthma outpatients. The outcomes of the study were number of hospital admissions,
      emergency visits, asthma symptoms, knowledge about asthma, lung function and
      quality of life. No effect was found regarding admission to hospital, emergency
      visits, prevalence of respiratory symptoms, knowledge of asthma or quality of
      life. However, forced exhaled volume in 1s (FEV(1)) increased significantly,
      mainly among the atopic subjects. In conclusion, an intervention with a limited
      asthma education program did not show an effect on asthma symptoms, asthma
      knowledge or quality of life parameters.

PMID- 15733509
TI  - Descriptive patterns of severe chronic pulmonary hypertension by chest
      radiography.
AB  - BACKGROUND: To find chest roentgenographic (CXR) features to help differentiate
      two representative diseases with severe chronic pulmonary hypertension (PH).
      STUDY SUBJECTS: Thirty-six consecutive patients with chronic thromboembolic PH
      (CTEPH), 38 with primary PH (PPH), and 37 with left heart disease and PH.
      METHODS: CXRs were reviewed about 6 features (left 2nd arc protrusion, right
      descending pulmonary artery diameter (rPAD), cardiothoracic ratio (CTR), right
      2nd arc width, avascular area and pleural abnormality). Hemodynamic data and the
      degree of tricuspid regurgitation (TR) on echocardiography were compared with CXR
      findings. RESULTS: The diagnostic pattern of CTEPH was the presence of one of two
      findings, an avascular area or marked rPAD (>20mm) together with pleuritic
      change. The diagnostic pattern of PPH was one of the two features; without
      pleuritic abnormality, marked left 2nd arc protrusion (>10mm) or moderate left
      2nd arc protrusion (5-10mm) with marked rPAD (<20mm). The sensitivity for the
      diagnosis of CTEPH among the three diseases was 78% and specificity was 92%. The
      sensitivity for the diagnosis of PPH was 45% and specificity was 88%. CTR and
      right 2nd arc width were related to the degree of TR in CTEPH and PPH.
      CONCLUSIONS: Characteristic roentgenographic findings can help differentiate two
      frequent diseases associated with chronic pulmonary hypertension and reflect the
      severity of disease.

PMID- 15733510
TI  - Clinical audit of subjects with snoring & sleep apnoea/hypopnoea syndrome fitted
      with mandibular repositioning splint.
AB  - Snoring and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are often treated
      with mandibular repositioning splints (MRS), but the efficacy and satisfaction of
      them has not been comprehensively addressed. A survey on the use of and
      satisfaction with MRS was posted to 177 patients referred by a hospital
      orthodontic department for custom-fitting of a MRS. Data were analysed using non
      parametric techniques. The response rate was 81% (n=144). Responders (30F, 114M)
      had mean (SD) age of 51 (11) years, apnoea+hypopnoea index (AHI) of 24 (21) per
      hr and Epworth Score of 10 (5) at diagnosis, and had been supplied with their MRS
      a median 7 (IQR 5-11) months previously. Fifty of the 144 patients (35%) had been
      offered continuous positive airway pressure (CPAP) treatment but had declined or
      abandoned this. Self-reported MRS use was 5 (2) h/night, with 74 of the 144
      patients (51%) continuing to use MRS at least occasionally at a median 7 months
      after fitting. Survival analysis showed 12% still using MRS at 12 months. Epworth
      score fell slightly with MRS therapy [-2.4 (3.5); P=0.005] and 7 daytime and 2
      nocturnal symptoms improved in MRS users (all P<0.05). Marital satisfaction did
      not change with MRS. Problems preventing MRS use in 70 non-users included: non
      retention (n=12), sore mouth (n=13) or jaw (n=7), difficulties falling asleep
      (n=10) or breathing (n=7), excessive salivation (n=4), dental damage (n=4) and
      other problems (n=3). Continued use of MRS therapy was associated with a higher
      number of teeth, low marital satisfaction perceived by partners and greater
      improvement in symptoms reported by patients and partners. Continuance with MRS
      may be low and linked to tolerance problems.

PMID- 15733511
TI  - Phenotypes of asthma revisited upon the presence of atopy.
AB  - Immunological studies claimed that atopic and non-atopic asthma share more
      similarities than differences. However, these two phenotypes of asthma are
      considered to be distinguishable upon distinct clinical patterns, which were not
      systematically assessed before in a large population. We studied characteristics
      discriminating atopic from non-atopic asthma among 751 asthmatic patients and 80
      factors were analysed in univariate and multivariate analysis. Age, age of onset
      of asthma, female/male ratio were higher in non-atopic (n=200) than in atopic
      (n=551) asthmatics. Familial asthma, seasonal symptoms, rhinitis, conjunctivitis,
      allergen-triggered symptoms, improvement in altitude, exercise-induced asthma
      were associated with atopy. Non-atopic asthmatics displayed lower FEV(1) and FVC.
      Smoking was more frequent and asthma was more severe in these patients. Younger
      age, early onset, male sex, rhinitis and smoking were independent factors
      discriminating atopic from non-atopic asthma. This study establishes in a large
      population of asthmatics that although similarities exist between atopic and non
      atopic asthma, two clinical phenotypes can still distinguish both kinds of
      asthma.

PMID- 15733512
TI  - Asthma outpatient education by multiple implementation strategy. Outcome of a
      programme using a personal notebook.
AB  - More than 10 years after publication, international guidelines remain poorly
      implemented. To better implement them, we need to develop new strategies adapted
      to the expectations of patients and health professionals outside hospital
      settings and to ensure better outpatient follow up in the community. We developed
      a bilingual education programme including a brochure designed to support an
      interdisciplinary health care network and measured hospitalisations (H), work
      absenteeism (WA), emergency visits (EV), asthma medication (AM) and quality of
      life (QL Juniper) before and 12 months after the intervention. All QL scores
      improved significantly in comparison with pre-intervention values. Health service
      use decreased dramatically when comparing the 12 months prior to and after the
      intervention(H: 35-8%, WA: 39-14%, EV: 88-53%). The final cost/benefit ratio of
      the programme was 1.96. Interdisciplinary implementation strategy of patient
      education is cost-effective, improves quality of life for asthmatics, and reduces
      strain on health services. Such a health care network does not require an
      expensive infrastructure and is better adapted to the reality and competences of
      clinical practice.

PMID- 15733513
TI  - Lung function in Greenlandic and Danish children and adolescents.
AB  - Respiratory morbidity in Inuit children is high. However, little is know
      regarding lung function measures in this population. The forced expiratory
      volumes in one second (FEV(1)) and forced vital capacity (FVC) in 888 Greenlandic
      Inuits (N=888) and Danes (N=477) aged 6-18 years were compared. Furthermore,
      associations between level of lung function and atopy and lifestyle factors were
      estimated in Greenlanders. The effect of height on FEV(1) and FVC was
      significantly different in Greenlanders and Danes, this difference in lung
      function increased with increasing height, and could not be explained by
      differences in age weight and BMI. Thus, Greenlanders taller than 130 cm had up
      to 300-400 ml higher FEV(1) and FVC compared with Danes of the same height. Among
      Greenlanders, those living in settlements had the highest levels of both FEV(1)
      and FVC. Greenlanders had elevated levels of FEV(1) and FVC compared with Danes.
      The Inuit having a shorter limb length in relation to trunk height may account
      for these differences. However, our finding that Greenlanders living in
      settlements had the highest lung function level also suggests a possible role of
      factors in the traditional Greenlandic lifestyle.

PMID- 15733514
TI  - Comparison of the effects of nebulised and inhaled salbutamol on breathlessness
      in severe COPD.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often
      report greater relief of breathlessness with nebulised bronchodilators than with
      the same medicine administered from a metered dose inhaler (MDI). This suggests
      that the nebulised medicines may have an effect on breathlessness over and above
      changes in lung function resulting from bronchodilatation. METHODS: Twenty-four
      subjects with COPD and breathlessness at rest participated in this randomised,
      crossover trial. The mean age was 72 years and the mean FEV(1) was 26% of
      predicted. Subjects were studied on four separate days. On two days they were
      treated with nebulised salbutamol and on the other 2 days with salbutamol from an
      MDI and spacer. With each method of delivery, local anaesthetic cream was applied
      to the face on one day and to the back of the hand on the other. RESULTS: Five
      minutes after administration of salbutamol the subjects were significantly less
      breathless with nebulised salbutamol but by 45 min both treatments resulted in
      equivalent relief. There was no difference between the treatments in the change
      in FEV(1) or VC and application of local anaesthetic to the face did not
      influence the response. CONCLUSION: There was a small early benefit with
      nebulised salbutamol but this was not sustained and was not affected by topical
      anaesthesia. The benefit of nebulisation does not appear to be large enough to
      warrant the routine, widespread use of nebulised bronchodilators for the
      treatment of stable COPD.

PMID- 15733515
TI  - Eosinophilic pericardial effusion in Churg-Strauss syndrome.

PMID- 15733516
TI  - Hyponatremia in liver cirrhosis: pathophysiological principles of management.
AB  - Hyponatremia is common in cirrhosis, where it impairs encephalopathy. It could be
      either due to excess water, or reduced Na, or a combination of both. The
      diagnosis can be established with clinical skills aided by simple data like
      weight, blood pressure and plasma electrolytes. The quantitative estimates of the
      water surfeit or solute deficit, easily performed with simple formulas and
      measurements, guide accurate and programmed treatment procedures, avoiding the
      occurrence of the ominous central pontine myelinolysis.

PMID- 15733517
TI  - Dose escalation of 5ASA: does it work?

PMID- 15733518
TI  - Effectiveness of colonoscopy.

PMID- 15733519
TI  - A prospective study of oesophageal 24-h ambulatory pH monitoring in patients with
      functional dyspepsia.
AB  - BACKGROUND: The diagnostic utility of 24-h oesophageal ambulatory pH monitoring
      in patients with functional dyspepsia has not been well established. AIMS: We
      performed a prospective study of oesophageal pH monitoring in patients with
      functional dyspepsia in order to assess whether a positive pH test might predict
      response to proton pump inhibitor therapy in a subset of functional dyspepsia
      patients. PATIENTS: Forty Helicobacter pylori-negative functional dyspepsia
      patients (35 males and 5 females, mean age (+/-S.E.M.) of 54+/-2.4 years) with
      predominantly unspecified dyspepsia subtype and normal distal oesophageal
      biopsies. METHODS: All subjects were randomised in a double-blind fashion to
      either omeprazole 20 mg/day or placebo daily for four weeks after 24-h pH
      monitoring. RESULTS: Twenty-four-hour pH monitoring was abnormal in 9 of the 21
      patients (43%) in the omeprazole group and 5/19 (26%) of the placebo group
      (p=NS). Patients who reported symptomatic improvement on the Gastrointestinal
      Symptom Rating Scale were no more likely to have abnormal scores on pH monitoring
      than patients who did not have symptomatic response. CONCLUSIONS: Although
      approximately one-third of functional dyspepsia patients will have abnormal
      profiles on 24-h ambulatory oesophageal pH monitoring, an abnormal score does not
      appear to predict response to proton pump inhibitor therapy in patients with
      unspecified functional dyspepsia.

PMID- 15733520
TI  - Long-term oral plus topical mesalazine in frequently relapsing ulcerative
      colitis.
AB  - BACKGROUND: In cross-sectional studies, it was demonstrated that the therapeutic
      effect of mesalazine is closely related to its mucosal concentration. AIM: This
      study was carried out to verify in a longitudinal study if it was possible to
      improve the clinical course of ulcerative colitis at high risk of recurrence by
      increasing mucosal mesalazine concentration. METHODS: Eighteen consecutive
      ulcerative colitis patients on continuous oral 5-ASA treatment (2.4-3.2 g/day) in
      clinical remission who had had at least four moderate to severe relapses in the
      preceding 2 years (referred period) were assigned to assume oral (3.2-4.8 g/day)
      and topical (4 g/day) mesalazine in order to increase mucosal drug concentration
      and were followed up for 2 years (study period). The localisation of disease was
      12 pancolitis, six left colitis. The number and severity of recurrences, number
      of visits and endoscopies, courses of steroids and days of hospitalisation were
      compared with those of the previous 2 years. Rank signed test for paired data was
      used for statistical analysis. RESULTS: The total number of recurrences was
      significantly lower during the study period in comparison with that of referred
      period (8 versus 80, respectively, p < 0.0001). No courses of steroids or
      hospitalisation were necessary during study period in comparison with those of
      referred period (0 versus 33, p < 0.0001; 0 versus 93, p = 0.03, respectively). A
      total number of 249 visits were done during the referred period and 116 during
      the study period (p < 0.0001) with a total of 87 endoscopies during referred
      period and 44 during study period (p < 0.0001). CONCLUSIONS: The continuous use
      of topical mesalazine associated with a high oral dosage significantly improves
      the clinical course of ulcerative colitis patients at high risk of relapse.

PMID- 15733521
TI  - Small doses of the unabsorbable substance polyethylene glycol 3350 accelerate oro
      caecal transit, but slow gastric emptying in healthy subjects.
AB  - BACKGROUND: Polyethylene glycol 3350 increases stool frequency and accelerates
      colonic transit. Used as a laxative, it proved effective in patients with normal
      and slow transit. Although free of severe side effects, it may cause nausea and
      vomiting. The effect of this substance on upper gut transit has not been studied.
      AIM: To investigate the effect of polyethylene glycol 3350 on gastric emptying
      and oro-caecal transit in 12 healthy subjects. METHODS: In a randomised
      controlled study, isosmotic polyethylene glycol 3350 electrolyte balanced
      solution, in the maximal recommended dose or isosmotic electrolyte solution, was
      administered after breakfast and lunch on separate days. Gastric half-emptying
      time and oro-caecal transit time were measured using [13C]-octanoate and lactose
      [13C] ureide breath tests. RESULTS: Isosmotic polyethylene glycol 3350
      electrolyte solution, as compared to isosmotic electrolyte solution, decreased
      oro-caecal transit time from 424+/-28 to 314+/-17 min (P = 0.001). Gastric half
      emptying time was significantly increased (84+/-6 min versus 127+/-14 min; P =
      0.006). CONCLUSION: Polyethylene glycol 3350 accelerate oro-caecal transit in
      healthy subjects, but also cause an important delay in gastric emptying. The
      delay in gastric emptying may be of clinical significance in patients who have
      associated gastroparesis.

PMID- 15733522
TI  - Interferon-induced depression: prevalence and management.
AB  - BACKGROUND: Interferon-induced depression ranges from 0 to 50%. Interferon
      schedule and a history of psychiatric illnesses are not enough to predict who
      will develop symptoms and who will not. AIMS: To assess the prevalence of
      depression during interferon therapy; to test whether Minnesota Multiphasic
      Personality Inventory is useful in clinical practice for the early identification
      of patients at risk of depression; whether and how the depression can be cured.
      PATIENTS: One hundred and eighty-five patients treated with interferon and
      ribavirin for chronic hepatitis C. METHODS: Before therapy, all patients
      underwent a Minnesota Multiphasic Personality Inventory and a clinical
      examination, specifically for the identification of depressive symptoms. RESULTS:
      Thirty-one patients developed a psychiatric disorder, 11 of them requiring
      treatment with anti-depressant drugs. Among the 18 patients with Minnesota
      Multiphasic Personality Inventory positive tests, 16 developed a psychiatric
      disorder, 8 of them a severe disorder (sensitivity of 0.58; 0.73 for severe
      disorders). Among the 154 who did not develop psychiatric side effects, 152 had a
      negative Minnesota Multiphasic Personality Inventory (specificity: 0.99). Severe
      psychiatric disorders were successfully treated with anti-depressant drugs.
      CONCLUSIONS: Psychiatric side effects are easy to see during interferon therapy.
      A psychiatric evaluation should be considered on all patients before treatment.
      If depression develops, it should be treated aggressively, and selective
      serotonin re-uptake inhibitors are the anti-depressants of choice.

PMID- 15733523
TI  - The Western immunoblotting pattern of anti-mitochondrial antibodies is
      independent of the clinical expression of primary biliary cirrhosis.
AB  - Anti-mitochondrial antibodies are the serological markers of primary biliary
      cirrhosis. We analysed the detailed anti-mitochondrial antibodies patterns to see
      whether the immunological specificities detected at the time of the diagnosis
      correlate with the histological, clinical and immunological expression of the
      disease. One hundred and thirty primary biliary cirrhosis patients were studied
      at the time of presentation/diagnosis. Anti-mitochondrial antibodies reactivity
      was dissected and evaluated by Western immunoblotting with bovine heart
      submitochondrial particles as antigenic source. Six different Western
      immunoblotting patterns have been identified with the following hierarchy:
      pattern A (anti-PDC-E2+anti-E3BP, 38.5%), pattern B (anti-PDC-E2+anti-E3BP+anti
      OGDC-E2, 20.8%), pattern C (anti-PDC-E2+anti-E3BP+anti-BCOADC-E2+anti-OGDC-E2,
      13.1%), pattern D (anti-PDC-E2+anti-E3BP+anti-BCOADC-E2, 6.9%), pattern E (anti
      BCOADC-E, 6.1%) and pattern F (anti-mitochondrial antibodies negative primary
      biliary cirrhosis, 14.6%). The different patterns were neither associated with
      peculiar clinical, biochemical, histological and immunological features nor with
      the Mayo Risk Score. The anti-mitochondrial antibodies pattern at presentation is
      independent of the stage of the liver disease; therefore, the Western
      immunoblotting characterisation of anti-mitochondrial antibodies does not seem to
      be helpful in identifying the clinical, biochemical or histological expression of
      primary biliary cirrhosis at the time of the diagnosis.

PMID- 15733524
TI  - Patient factors influencing the completion rate in colonoscopy.
AB  - BACKGROUND: Since its introduction in the late 1960s, the technology of
      colonoscopy has developed rapidly, and the competence of the endoscopists has
      increased. Still, a complete colonoscopy is not always possible to perform. AIM:
      To assess, in a population-based setting, which patient factors influence the
      success rate. PATIENTS AND METHODS: All colonoscopy records during 1979-1995 in
      one Swedish county (population 258,000) were retrieved. Information was obtained
      about each patient's sex and age, date of examination, the endoscopist and
      indications for colonoscopy, findings, type of colonoscopy and reasons for an
      incomplete colonoscopy. Results were assessed by univariate and multivariate
      analyses. RESULTS: Of 5145 colonoscopies, 4153 (81%) were complete. Completion
      rates were influenced by (odds ratio for completion [95% confidence intervals]):
      sex, male versus female (2.00 [1.39-2.86]); age, youngest quartile versus oldest
      quartile (1.49 [1.04-2.13]); indication for colonoscopy, previous colonic surgery
      or long-standing colitis versus other indications (2.08 [1.23-3.45]); and
      diverticulosis, presence versus no presence (0.79 [0.62-0.99]). The time period
      (proxy variable for the development of endoscopes) had no impact on completion
      rates. CONCLUSIONS: The completion rate was lower than that has been reported
      from previous hospital-based studies. Lower completion rates were found in women,
      older patients and in patients with diverticulosis. Higher completion rates were
      noted in patients with previous colonic surgery and long-standing colitis. The
      completion rates were not influenced by the development of the endoscopes.

PMID- 15733525
TI  - A survey of open-access endoscopy in primary health care centres: outcome of
      gastric carcinoma patients diagnosed by general practitioners compared with
      hospital-referred endoscopy.
AB  - BACKGROUND: We examined open-access endoscopy service based on general
      practitioner endoscopists. METHODS: We compared the survival of the gastric
      carcinoma patients originally diagnosed in health care centres by general
      practitioner endoscopists and hospital outpatient clinic by specialists. RESULTS:
      A total of 159 gastric carcinoma cases diagnosed during 1996-2000 were included
      in to the present study. Of them, 58% (N = 92) and 42% (N = 67) were detected by
      general practitioners and specialists, respectively. We observed no difference in
      the mean age of patients (71.3 years versus 71.4 years, p = 0.97) and stage of
      tumours [15% (N = 14) versus 21% localised tumours (N = 14, p = 0.30)] between
      cases diagnosed by general practitioners and specialists. The number of patients
      who underwent radical extirpation were 14% (N = 13) and 19% (N = 13, p = 0.38),
      respectively. After a minimum follow-up of 3.5 years, 29 patients (18%) were
      alive. The mean survival time of hospital-diagnosed carcinoma patients was longer
      (23.6 months versus 18.7 months, p = 0.23). Eight patients had undergone hospital
      referred gastroscopy less than 3 years before cancer diagnosis. In multivariate
      analysis, radical extirpation of carcinoma (odds ratio 0.11, 95% confidence
      interval 0.04-0.28) predicted survival; whereas age (odds ratio 1.03 per year,
      95% confidence interval 0.99-1.07 per year), female sex (odds ratio 1.785, 95%
      confidence interval 0.71-4.81) and the open-access endoscopy based on general
      practitioner endoscopists (odds ratio 1.48, 95% confidence interval 0.60-3.65)
      predicted neither survival nor carcinoma-related death. CONCLUSION: No
      significant difference was detected in the outcome of gastric cancer patients
      diagnosed in primary care centres by general practitioner endoscopists and in
      hospital outpatient clinic by specialists.

PMID- 15733526
TI  - Case report: colonic manometry reveals abnormal propulsive behaviour after
      anterior resection of the rectum.
AB  - Anterior resection of the rectum is a frequent surgical procedure. However,
      abnormal bowel habits following this procedure are frequently reported. The
      functional evaluation of these patients is usually limited to the anorectal area.
      By means of colonic manometry, we have evaluated a patient with frequent urge for
      defecation and increased bowel frequency following anterior resection of the
      rectum with straight coloanal anastomosis and almost normal anorectal function.
      Analysis of the tracing revealed a reduction of contractile segmental activity
      and much more high-amplitude propagated contractions than which occur in healthy
      subjects. These high-amplitude propagated contractions, representing the
      manometric equivalent of mass movements, were always in association with urge for
      defecation and, sometimes, with loose stools. High-amplitude simultaneous
      contractions were also observed. We feel that the surgical resection of a
      potential physiological brake may be responsible for these observations.

PMID- 15733527
TI  - Ringed oesophagus and idiopathic eosinophilic oesophagitis in adults: an
      association in two cases.
AB  - Ringed oesophagus is an increasingly recognised finding in young people
      presenting with dysphagia and may be related to eosinophilic oesophagitis.
      Recently, hypotheses regarding potential aetiologies have been proposed but these
      have not been systemically tested in the majority of reported cases. We report
      two cases very similar in clinical history and endoscopic findings. An
      association with gastro-oesophageal reflux disease or motility abnormalities of
      the oesophagus were ruled out in both. Histological analysis revealed high
      density infiltration of the oesophageal mucosa by eosinophils and excluded gastro
      duodenal involvement. Examinations of the oesophagus at the time of low frequency
      dysphagia, some years before presentation to our centre, did not show rings,
      suggesting that multiple rings are a possible late complication of eosinophilic
      oesophagitis. Oesophageal dilatation effectively relieved dysphagia in our two
      patients.

PMID- 15733528
TI  - The suspension of an announced trial on relapse prevention in Crohn's ileitis
      with a 5-ASA formulation in microgranular form.

PMID- 15733529
TI  - Alcohol abuse and occult HBV-a risk factor for hepatocellular carcinoma.

PMID- 15733530
TI  - Respiratory nosocomial infections in the medical intensive care unit.
AB  - Intensive care unit (ICU)-acquired lower respiratory tract infections include
      acute tracheobronchitis and hospital-acquired and ventilator-associated pneumonia
      (VAP). Nosocomial pneumonia is the second most common hospital-acquired infection
      and the leading cause of death in hospital-acquired infections. The mortality
      rate in VAP ranges from 24% to 76% in several studies. ICU ventilated patients
      with VAP have a 2- to 10-fold higher risk of death than patients without it.
      Early oropharyngeal colonization is pivotal in the etiopathogenesis of VAP. The
      knowledge of risk factors for VAP is important in developing effective preventive
      programs. Once the physician decides to treat a suspected episode of ICU-acquired
      pneumonia, some issues should be kept on mind: first, the adequacy of the initial
      empiric antibiotic therapy; second, the modification of initial inadequate
      therapy according to microbiological results; third, the benefit of combination
      therapy; and finally, the duration of the antimicrobial treatment. Additionally,
      a protocolized work-up to identify the causes of non-response to treatment is
      mandatory. All these issues are discussed in depth in this article.

PMID- 15733531
TI  - Site interdependence attributed to tertiary structure in amino acid sequence
      evolution.
AB  - Standard likelihood-based frameworks in phylogenetics consider the process of
      evolution of a sequence site by site. Assuming that sites evolve independently
      greatly simplifies the required calculations. However, this simplification is
      known to be incorrect in many cases. Here, a computational method that allows for
      general dependence between sites of a sequence is investigated. Using this
      method, measures acting as sequence fitness proxies can be considered over a
      phylogenetic tree. In this work, a set of statistically derived amino acid
      pairwise potentials, developed in the context of protein threading, is used to
      account for what we call the structural fitness of a sequence. We describe a
      model combining statistical potentials with an empirical amino acid substitution
      matrix. We propose such a combination as a useful way of capturing the complexity
      of protein evolution. Finally, we outline features of the model using three
      datasets and show the approach's sensitivity to different tree topologies.

PMID- 15733532
TI  - Rapid expansion of killer cell immunoglobulin-like receptor genes in primates and
      their coevolution with MHC Class I genes.
AB  - The gene family of killer cell immunoglobulin-like receptors (KIRs) in primates
      provides the first line of defense against virus infection and tumor
      transformation. Interacting with MHC class I molecules, KIRs can regulate the
      cytotoxic activity of natural killer (NK) cells and distinguish the tumor and
      virus infected cells from normal body cells. Phylogenetic analysis and comparison
      of domain structures identified three major groups of KIR genes (group I, II, and
      III genes). These groups of KIR genes, generated by a series of gene
      duplications, have acquired different MHC-binding specificity. Inference of
      ancestral KIR sequences suggested that the functional divergence of group I genes
      from group II genes occurred by positive selection at the MHC-binding sites after
      duplication. Our evolutionary study has shown that group I genes diverged from
      group II genes about 17 million years ago (Mya) apparently after separation of
      hominoids from Old World (OW) monkeys. Around the same time, gene duplication
      generating the class I MHC-C locus appears to have occurred. These findings
      suggest that KIR and MHC class I genes have coevolved as an interacting system.
      The KIR gene family has experienced a rapid expansion in primate species. The
      rate of expansion of this gene family seems to be one of the highest among all
      hominoid gene families. The KIR gene family is also subject to birth-and-death
      evolution.

PMID- 15733533
TI  - T-helper type 2 cell-specific expression of the ST2 gene is regulated by
      transcription factor GATA-3.
AB  - ST2 is a member of the interleukin-1 receptor family and is expressed in type-2 T
      helper (Th2) cells. Here, we have studied the molecular mechanism responsible for
      the transcriptional regulation of the ST2 gene in Th2 cells using a mouse thymoma
      cell line, EL-4. The ST2 gene has distal and proximal promoters. ST2 mRNA was
      produced from the distal promoter in EL-4 cells stimulated with both phorbol 12
      myristate 13-acetate (PMA) and dibutyryl cAMP (Bt2cAMP). The region of
      approximately 100 bp upstream of transcription start site, containing two GATA
      consensus sites, was indispensable for the activation of the distal promoter in
      reporter gene analysis. An electrophoretic mobility shift assay showed that
      transcription factor GATA-3 bound one of the GATA consensus sites (from -84 to 
      79) with nuclear extracts from PMA plus Bt2cAMP-stimulated EL-4 cells. The
      overexpression of GATA-3 enhanced the activity of the distal promoter. On the
      other hand, mutations of the GATA consensus site canceled out the enhancement by
      GATA-3. These data suggest that GATA-3 is an important transcription factor for
      the expression of the ST2 gene in Th2 cells.

PMID- 15733534
TI  - Promoter analyses of SCC antigen genes.
AB  - SCC antigen (SCCA) has been used as a tumor marker for squamous cell carcinoma.
      Analyses of the SCCA1 and SCCA2 genes, which are almost identical, and their
      promoters have been reported. Recently it was found that both SCCAs were
      stimulated by interleukin (IL)-4 and IL-13. Here we analyzed the promoter
      activity of both SCCAs in the 5'-flanking region, exon 1, and intron 1 to
      evaluate a putative STAT6 binding site. The addition of intron 1 to the
      luciferase assay constructs including the 5'-flanking region significantly
      augmented the promoter activity of both SCCA1 and SCCA2. Furthermore, deletion
      analyses of intron 1 revealed that a 50-bp fragment of intron 1 that includes
      putative STAT6 binding site was responsible for the increased promoter activity.
      Although the sequences of SCCA1 and SCCA2 are very similar in the 5'-flanking
      region, the analysis of the -337 single nucleotide polymorphism of SCCA2
      indicated that this polymorphism may underlie the difference in promoter activity
      between SCCA1 and SCCA2.

PMID- 15733535
TI  - SNAMA, a novel protein with a DWNN domain and a RING finger-like motif: a
      possible role in apoptosis.
AB  - We have characterized SNAMA a hitherto uncharacterized Drosophila protein that
      appears to play a role in apoptosis. SNAMA (something that sticks like glue) is a
      1231 amino acid protein with a conserved 76 residue N-terminal domain called
      Domain With No Name (DWNN). The DWNN domain was first identified in cytotoxic T
      Cell-resistant CHO cells using promoter trap mutagenesis to screen for genes
      involved in apoptosis. Subsequently, this domain was identified in other
      eukaryotic organisms including animals and plants. The SNAMA transcript is
      abundant early in embryogenesis but reduced in older embryos and in adult males
      and females. Human and mouse homologues of SNAMA are known to bind to p53 and to
      the retinoblastoma protein (Rb) suggesting a role in transcriptional regulation
      and cell cycle control. We took advantage of a P-element insertion line in which
      the P-element is inserted in the first intron, to investigate the biological
      function of the gene. These mutants are lethal when homozygous. Apoptosis appears
      early during embryogenesis and is observed virtually throughout the gastrula. The
      DWNN domain has a ubiquitin-like fold and may interact with a subset of cellular
      proteins. There is also a conserved RING finger-like motif along the sequence of
      SNAMA following a C2HC zinc finger.

PMID- 15733536
TI  - Ozone-induced paradoxical sleep decrease is related to diminished acetylcholine
      levels in the medial preoptic area in rats.
AB  - Ozone (O3) produces significant effects on sleep, characterized specially by a
      decrease in paradoxical sleep (PS) and increase in slow-wave sleep (SWS), which
      in turn represent a sleep-wake cycle disruption. On the other hand, neuronal
      activity recorded in the cholinoceptive hypothalamic medial preoptic area (MPO)
      has been involved in the regulation of sleep. However, there is no direct
      evidence on the role that acetylcholine (Ach) release in the MPO plays in the
      sleep-wake cycle. In order to study this relation, we measured the Ach
      concentration in dialysates collected from MPO in rats exposed to coal-filtered
      air (clean air) for 48 h and in rats exposed to clean air for 24 h followed by 24
      h of O3 exposure to 0.5 ppm. Polygraphic sleep records were taken simultaneously
      to neurochemical sampling. O3 was employed to disrupt the sleep-wake cycle and
      relate these changes with concomitant disruptions in Ach concentration dialyzed
      from MPO. A clear circadian pattern of Ach concentration was observed in
      dialysates from MPO and also in PS, SWS and wakefulness of rats exposed to
      filtered air. However, O3 exposure decreased the PS by 65% (Mann-Whitney's U
      test, p<or=0.0003) and a concomitant decrease of extracellular Ach of 58%
      (p<or=0.0239) was observed during the light phase. These changes were maintained
      during the dark phase, although it was also observed that slow-wave sleep
      increased by 75% (p<or=0.0013) while wakefulness was decreased in 35%
      (p<or=0.0007). We conclude that Ach release in MPO follows a circadian rhythm
      that is disrupted by O3 exposure, and these changes are strongly associated with
      the O3-induced PS disruptions.

PMID- 15733537
TI  - Diphenyl diselenide reverses cadmium-induced oxidative damage on mice tissues.
AB  - The concept that selenium-containing molecules may be better antioxidants than
      classical antioxidants, has led to the design of synthetic organoselenium
      compounds. In the present investigation subchronic deleterious effects of cadmium
      intoxication in mice and a possible protective effect of diphenyl diselenide
      (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g)
      received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A
      number of toxicological parameters in blood, liver, kidney, spleen and brain of
      mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D)
      activity, lipid peroxidation and ascorbic acid content, the parameters that
      indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were
      also determined. The results demonstrated that cadmium caused inhibition of delta
      ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy
      was effective in restoring enzyme activity in all tissues. A reduction in
      ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium
      treated mice and (PhSe)2 was only effective in improving this reduction in
      kidney. An increase of lipid peroxidation induced by cadmium was noted in liver
      (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring
      TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99
      times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was
      effective in restoring AST activity at control level. (PhSe)2 did not present
      toxic effects when plasma parameters were evaluated. The results suggest that the
      administration of an antioxidant (PhSe)2, during cadmium intoxication may provide
      beneficial effects by reducing oxidative stress in tissues.

PMID- 15733538
TI  - Oxidative stress is involved in inhibition of copper on histone acetylation in
      cells.
AB  - Our previous study demonstrates that copper induces histone hypoacetylation by
      inhibiting histone acetyltransferase (HAT) activity. However, it lacks direct
      evidences whether copper-inhibited histone acetylation right contributes to the
      toxicity of copper. Exposure of human leukemia cells (HL-60) to Cu2+ resulted in
      cell proliferation arrest and a concentration- and time-dependent decrease of
      histone acetylation. At the same time, Cu2+-induced significant increase of H2O2
      and O2.- generation via a concentration- and time-dependent manner too. The
      histone acetylation was efficiently suppressed by exogenous H2O2, and enhanced by
      superoxide dismutase (the scavenger of O2.-), catalase (the scavenger of H2O2) or
      the combination of both, indicating that Cu2+ at least partially inhibited
      histone acetylation through triggering oxidative stress. Further studies found
      that sodium butyrate, the inhibitor of histone deacetylase (HDAC), which had no
      obvious effect on oxidative stress but increased histone acetylation at the
      concentration of 50 microM, attenuated Cu2+-inhibited cell proliferation,
      indicating that histone acetylation inhibition is simultaneously involved in the
      cytotoxicity of Cu2+. Considering the important role of histone acetylation in
      gene transcription and regulation of cell fate, the present study may open a new
      door to further understand the mechanism of Cu2+-induced toxicity.

PMID- 15733539
TI  - Application of quantitative structure-toxicity relationships for acute NSAID
      cytotoxicity in rat hepatocytes.
AB  - Non-steroidal anti-inflammatory agents (NSAIDs) are widely used for pain relief.
      However, they have been associated with harmful and sometimes fatal side effects.
      Usually, the target organs are the GI tract and liver. In this study, we have
      investigated the physicochemical requirements of 21 NSAIDs for glucuronidation
      and cytotoxicity by quantitative structure-toxicity relationships (QSTRs) in
      isolated rat hepatocytes. Furthermore, we have investigated the contrast in
      physicochemical variables that correlated with NSAID-induced hepatocyte
      cytotoxicity when glucuronidation was inhibited with borneol. The competitive
      inhibition of hepatocyte p-nitrophenol glucuronidation by NSAIDs was determined
      by HPLC. Glucuronidation-inhibited hepatocytes were more susceptible to NSAID
      induced cytotoxicity. Also, we found a parabolic correlation between
      lipophilicity and the inhibition of glucuronidation for a subset of NSAIDs. For
      NSAIDs with a benzoic acid moiety, cytotoxicity also correlated parabolically
      with lipophilicity, but correlated linearly with the HOMO-LUMO gap, and the first
      order valence connectivity index. The cytotoxicity of NSAIDs with a phenylacetic
      acid (or propionic acid) substructure also correlated with lipophilicity, but not
      with the HOMO-LUMO gap. Our findings indicated that the inhibition of
      glucuronidation resulted in increased NSAID cytotoxicity, suggesting that acyl
      glucuronide metabolites were acutely less cytotoxic. Also, comparative QSTRs
      revealed that benzoic acid NSAIDs may form cytotoxic radical metabolites
      (parameterized by the HOMO-LUMO gap) or alter mitochondrial respiration
      (parameterized by the connectivity index), whereas phenylacetic acid derived
      NSAIDs may form different cytotoxic metabolites, since they did not correlate
      with these parameters. In summary, we have used QSTRs as a tool to distinguish
      the cytotoxic mechanism of two groups of NSAIDs, which, if analyzed together as
      one group, did not reveal such mechanism-based differences.

PMID- 15733540
TI  - Comparative excretion and tissue distribution of selenium in mice and rats
      following treatment with the chemopreventive agent 1,4
      phenylenebis(methylene)selenocyanate.
AB  - In a previous preliminary investigation, we reported on the excretion, tissue
      disposition and metabolism of the chemopreventive agent 1,4
      phenylenebis(methylene)selenocyanate (p-XSC) in the rat, but similar studies in
      the mouse have not been explored. Following the oral administration of p-XSC (50
      micromol/kg body weight), selenium excretion in feces was comparable to that in
      urine in mice, but in rats, feces was the major route of excretion.
      Tetraselenocyclophane (TSC) was the major metabolite detected in mouse and rat
      feces. In both species, levels of selenium in exhaled air were negligible. At
      termination, in the mouse, the stomach had the highest selenium content followed
      by liver and blood, but lung and kidney contained negligible levels of selenium;
      in the rat, the selenium level in liver was the highest followed by kidney,
      stomach, blood and lung. The identification of TSC as a fecal metabolite in both
      species let us to postulate the following metabolic pathway: p-XSC-->glutathione
      conjugate (p-XSeSG)-->a selenol (p-XSeH)-->TSC. Since the glutathione conjugate
      appears to be the proximal precursor for the selenol metabolite that may be an
      important intermediate in cancer chemoprevention, we report for the first time
      the synthesis of p-XSeSG and its other potential metabolites, namely the cysteine
      and N-acetylcysteine-conjugates of p-XSC. HPLC analysis of the urine and bile
      showed a few metabolites of p-XSC; none of which eluted with the synthetic
      standards described above. When we examined the conversion of p-XSC and p-XSeSG
      in vitro using rat cecal microflora, TSC was formed from p-XSeSG but not from p
      XSC. The formation of TSC from p-XSC in vivo but not in vitro suggests that p-XSC
      needs to be metabolized to p-XSeSG or an intermediate derived from its further
      metabolism. Thus, p-XSeSG was given orally to rats and the results showed that
      the pattern of selenium excretion after p-XSeSG treatment was similar to that of
      p-XSC; TSC was also identified as a fecal metabolite of p-XSeSG. It may be that
      the conversion of p-XSeSG to TSC is too facile, or the mere conjugation of p-XSC
      with glutathione does not occur in rats and mice.

PMID- 15733541
TI  - The metabolism of nonane, a JP-8 jet fuel component, by human liver microsomes,
      P450 isoforms and alcohol dehydrogenase and inhibition of human P450 isoforms by
      JP-8.
AB  - Nonane, a component of jet-propulsion fuel 8 (JP-8), is metabolized to 2-nonanol
      and 2-nonanone by pooled human liver microsomes (pHLM). Cytochrome P450 (CYP)
      isoforms 1A2, 2B6 and 2E1 metabolize nonane to 2-nonanol, whereas alcohol
      dehydrogenase, CYPs 2B6 and 2E1 metabolize 2-nonanol to 2-nonanone. Nonane and 2
      nonanol showed no significant effect on the metabolism of testosterone, estradiol
      or N,N-diethyl-m-toluamide (DEET), but did inhibit carbaryl metabolism. JP-8
      showed modest inhibition of testosterone, estradiol and carbaryl metabolism, but
      had a more significant effect on the metabolism of DEET. JP-8 was shown to
      inhibit CYPs 1A2 and 2B6 mediated metabolism of DEET, suggesting that at least
      some of the components of JP-8 might be metabolized by CYPs 1A2and/or 2B6.

PMID- 15733542
TI  - Quinone reductase 2 substrate specificity and inhibition pharmacology.
AB  - Quinone reductase 2 is a mammalian cytosolic FAD-dependent enzyme, the activity
      of which is not supported by conventional nicotinamide nucleotides. An endobiotic
      substrate has never been reported for this enzyme nor a set of molecular tools,
      such as inhibitors. In the present work, we used the recombinant human enzyme,
      expressed in CHO cells for the systematic screening of both co-substrates and
      substrates. The co-substrates survey showed that the natural occurring compound,
      N-ribosylnicotinamide, was a poor co-substrate. The synthetic N
      benzylnicotinamide is a better one compared to any other compounds tested. We
      found that tetrahydrofolic acid acted as a co-substrate for the reduction of
      menadione catalysed by quinone reductase 2, although with poor potency (Km
      approximately 2 mM). Among a series of commercially available quinones, a single
      one was found to be substrate of quinone reductase 2, in the presence of N
      benzyldihydronicotinamide: coenzyme Q0. Finally, we tested a series of 197
      flavonoids as potential inhibitors. We found apigenin, genistein or kaempferol as
      good inhibitor of quinone reductase 2 activity with IC50 in the 100 nM range.
      These compounds, co-substrate, substrate and inhibitors will permit to better
      know this enzyme, the role of which is still poorly understood.

PMID- 15733543
TI  - Inhibition of cyclooxygenase-2 gene expression by the heat shock response in J774
      murine macrophages.
AB  - The heat shock response is a highly conserved mechanism of protection elicited in
      the cell by various kinds of stimuli, such as heat, sodium arsenite, oxidants and
      inflammation. Among the mechanisms potentially involved in mediating the
      protective effects of hsp, one of the most investigated is the inhibition of pro
      inflammatory gene expression such as inducible nitric oxide synthase (iNOS) and
      inflammatory cytokines. Nevertheless, data about the effects of heat shock
      response on cyclooxygenase-2 expression in activated macrophages are so far not
      available in literature. The aim of this study was to investigate the changes in
      cyclooxygenase-2 expression following lipopolysaccharide stimulation of heat
      shocked J774 murine macrophages. We found, by Western blotting analysis and
      reverse transcription-polymerase chain reaction analysis (RT-PCR), that the
      lipopolysaccharide-induced cyclooxygenase-2 gene expression was reduced in heat
      shocked cells. Such a reduction was associated to activation of heat shock
      factor, increased levels of heat shock protein 72 and inhibition of
      lipopolysaccharide-induced nuclear factor-kappaB binding activity. These data
      suggest that the heat shock response inhibits cyclooxygenase-2 gene expression at
      transcriptional level, i.e. by preventing the activation of nuclear factor
      kappaB, and provide additional information about mechanism(s) underlying the anti
      inflammatory effect of the heat shock proteins.

PMID- 15733544
TI  - Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors
      by a competitive mechanism.
AB  - Effects of cholinergic drugs on human alpha4beta2 nicotinic acetylcholine
      receptors expressed in Xenopus oocytes have been investigated in
      electrophysiological and ligand binding experiments. Atropine, scopolamine,
      physostigmine, and tacrine combine potentiation of ion current induced by low
      concentrations of acetylcholine with inhibition of ion current evoked by high
      concentrations of acetylcholine. Rivastigmine, galanthamine, and dichlorvos cause
      only inhibition of ion current evoked by low concentrations of acetylcholine.
      Binding experiments show that the potentiating cholinergic drugs atropine,
      scopolamine, and physostigmine are competitive ligands of human alpha4beta2
      nicotinic acetylcholine receptors. Conversely, the inhibitory cholinergic drugs
      galanthamine and rivastigmine are non-competitive. The non-competitive drugs are
      not allosteric, since they do not affect the saturation curve of the radioligand
      [3H]cytisine. Effects of potentiating cholinergic drugs on nicotinic
      acetylcholine receptors are consistent with and predicted by a model comprising
      competitive drug effects at two equivalent agonist recognition sites on the
      nicotinic acetylcholine receptor combined with non-competitive ion channel block.

PMID- 15733545
TI  - Caffeine induced Ca2+ release and capacitative Ca2+ entry in human embryonic
      kidney (HEK293) cells.
AB  - The potential role of endogenous ryanodine receptor (RyR) in modulating Ca2+
      handling in HEK293 cells is controversial. Using Fura2/AM, here we provide
      evidence that caffeine can induce Ca2+ release from inositol 1,4,5-trisphosphate
      receptor-sensitive stores and Ca2+ entry in early passage numbers of HEK293
      cells, but not in late passage ones. Ryanodine blocks caffeine-mediated effect,
      whereas 4-chloro-m-cresol can mimic these effects. In contrast, an increase in
      cyclic AMP or activation of voltage-dependent Ca2+ channels does not induce
      detectable alteration in intracellular Ca2+. Importantly, immunoblotting and
      staining have revealed that endogenous RyR expression is more abundant in the
      early than in the late passage cells. Additionally, similar to carbachol, Ca2+
      entry in response to caffeine is blocked by capacitative Ca2+ entry inhibitors.
      These results indicate that the endogenous RyR in HEK293 cells can function as
      Ca2+ release channels and mediate capacitative Ca2+ entry, but they may be
      reduced due to cell passage.

PMID- 15733547
TI  - Involvement of spinal serotonin receptors in the regulation of intraspinal
      acetylcholine release.
AB  - Stimulation of spinal serotonin (5-HT) receptors results in analgesia and release
      of acetylcholine. We investigated the involvement of 5-HT1, 5-HT2, and 5-HT3
      receptor subtypes in the regulation of spinal acetylcholine release. A spinal
      microdialysis probe was placed dorsally at about the C5 level in anaesthetized
      rats. The selective serotonin reuptake inhibitor citalopram was found to increase
      acetylcholine release when infused via the microdialysis probe. Several doses of
      the 5-HT receptor agonists 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT, 5
      HT1A), 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5
      one dihydrochloride (CP93129, 5-HT1B), alpha-methyl-5-hydroxytryptamine maleate
      (m5-HT, 5-HT2), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 5-HT2C), and
      1-(m-chlorophenyl)-biguanide (5-HT3) were subsequently infused via the
      microdialysis probe. Only 8-OH-DPAT, CP93129, and m5-HT increased acetylcholine
      release dose dependently. The 5-HT1A receptor selective antagonist (S)-N-tert
      butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide hydrochloride
      and the 5-HT2A receptor selective antagonist ketanserin tartrate inhibited the 8
      OH-DPAT and the m5-HT induced acetylcholine release. The results suggest that 5
      HT1A and the 5-HT2A receptors are involved in the regulation of acetylcholine
      release in the spinal cord.

PMID- 15733546
TI  - BU74, a complex oripavine derivative with potent kappa opioid receptor agonism
      and delayed opioid antagonism.
AB  - In the search for opioid agonists with delayed antagonist actions as potential
      treatments for substance abuse, the bridged morphinan BU74 (17-cyclopropylmethyl
      3-hydroxy-[5beta,7beta,3',5']-pyrrolidino-2'[S]-phenyl-7alpha-methyl-6,14
      endoetheno morphinan) (3f) was synthesized. In isolated tissue and [35S]GTPgammaS
      opioid receptor functional assays BU74 was shown to be a potent long-lasting
      kappa opioid receptor agonist, delta opioid receptor partial agonist and mu
      opioid receptor antagonist. In antinociceptive tests in the mouse, BU74 showed
      high efficacy and potent kappa opioid receptor agonism. When its agonist action
      had waned BU74 became an antagonist of kappa and mu opioid receptor agonists in
      the tail flick assay and of delta, kappa and mu opioid receptor agonists in the
      acetic acid writhing assay. The slow onset, long-duration kappa opioid receptor
      agonist effects of BU74 suggests that it could be a lead compound for the
      discovery of a treatment for cocaine abuse.

PMID- 15733548
TI  - Sensitization to morphine withdrawal in guinea-pigs.
AB  - The aim of this study was to determine whether sensitization occurred to morphine
      withdrawal. Guinea-pigs were treated twice daily with increasing doses of
      morphine (10-100 mg/kg s.c.) for 3 days followed by injection of morphine 100
      mg/kg on the fourth day. Sixty min after the last morphine injection, animals
      were withdrawn from morphine with naltrexone, 15 mg/kg s.c., and locomotor
      activity and all other behaviours scored over 90 min. Animals were then rested
      for 3 days. This procedure was repeated twice over the next 2 weeks. Control
      animals were treated with saline for the first two treatment cycles. Guinea-pigs
      subjected to three cycles of morphine withdrawal showed a significant increase in
      the total number of withdrawal behaviour counts over the 90-min observation
      period following the third cycle of withdrawal compared with the first and second
      withdrawal cycles. However, locomotor activity, a major sign of morphine
      withdrawal in guinea-pigs, was not significantly increased. Fos-LI was markedly
      increased in the repeatedly withdrawn animals in several brain regions, including
      amygdala, dorsal striatum, thalamus, ventral tegmental area, and ventrolateral
      periaqueductal gray area. It is concluded that sensitization to morphine
      withdrawal occurs in guinea-pigs.

PMID- 15733549
TI  - Stress and central Urocortin increase anxiety-like behavior in the social
      interaction test via the CRF1 receptor.
AB  - Corticotropin releasing factor (CRF) and Urocortin are important
      neurotransmitters in the regulation of physiological and behavioral responses to
      stress. Centrally administered CRF or Urocortin produces anxiety-like responses
      in numerous animal models of anxiety disorders. Previous studies in our lab have
      shown that Urocortin infused into the basolateral nucleus of the amygdala
      produces anxiety-like responses in the social interaction test. Subsequently, in
      the current study we prepared a specific CRF1 receptor antagonist (N
      Cyclopropylmethyl-2,5-dimethyl-N-propyl-N'-(2,4,6-trichloro-phenyl)-pyrimidine
      4,6-diamine, NBI3b1996) to examine in this paradigm. This CRF1 receptor
      antagonist inhibited the ex vivo binding of 125I-sauvagine to rat cerebellum with
      an ED50 of 6 mg/kg, i.p. NBI3b1996 produced a dose-dependent antagonism of
      Urocortin-induced anxiety-like behavior in Social Interaction test with an ED50
      of 6 mg/kg, i.p. The compound had no effect on baseline social interaction. In
      addition, the CRF1 receptor antagonist prevented the stress-induced decrease in
      social interaction. These results provide further support for the CRF1 receptor
      in anxiety-like behavior and suggest this pathway is quiescent in unstressed
      animals.

PMID- 15733550
TI  - Maternal caffeine intake impairs MK-801-induced hyperlocomotion in young rats.
AB  - Here we have investigated the effects of maternal caffeine intake (1 g/l) on MK
      801-induced hyperlocomotion in rat pups. Animals submitted to caffeine treatment
      during the gestational and lactational period were separated in two groups:
      caffeine-treated group (up to 21 days old) and washout group (caffeine treatment
      up to 7 days old). MK-801 (0.25 mg/kg, i.p.) promoted hyperlocomotion in control
      rats, but this stimulatory effect was significantly decreased in caffeine-treated
      and washout groups. The permanent effect after caffeine withdrawal suggests
      durable or adaptive changes during neurodevelopment, mainly on adenosine
      receptors or neurotransmitter systems modulated by adenosine, such as the
      glutamatergic system.

PMID- 15733551
TI  - Periadolescent nicotine exposure causes heterologous sensitization to cocaine
      reinforcement.
AB  - There is increasing concern that abuse of tobacco during periadolescence
      increases the potential for later abuse of other drugs. To test this hypothesis,
      Sprague-Dawley rats received once-daily injections of either water or 0.4 mg/kg
      nicotine from postnatal day 35 through 44. Beginning on postnatal day 80, animals
      were tested in a 12-day cocaine-induced conditioned place preference (CPP)
      paradigm. Prior nicotine treatment enhanced the dose-response to cocaine. CPP
      training with 3.0 mg/kg i.p. cocaine increased time in drug-paired chambers by
      50% in control rats and 94% in nicotine-exposed animals. Thus, periadolescent
      nicotine exposure produced long-term sensitization to an indirect-acting dopamine
      agonist.

PMID- 15733552
TI  - Effect of ischemia duration and nitric oxide on coronary vasoconstriction after
      ischemia-reperfusion.
AB  - The effects of the duration of ischemia on coronary vasoconstriction after
      ischemia-reperfusion were analysed in rat hearts. After 15, 30 or 45 min of
      global zero-flow ischemia and 15 min reperfusion, the coronary response to
      endothelin-1 (10(-10)-10(-7) M) and the thromboxane A2 analogue 9,11-dideoxy
      1a,9a-epoxymethanoprostaglandin F2alpha (U46691, 10(-8)-10(-6) M) was recorded.
      Vasoconstriction induced by endothelin-1 only increased after short 15 min
      periods of ischemia. In contrast, the vasoconstriction induced by U46619 remained
      unmodified by short ischemias but was reduced after longer periods of ischemia
      (30 and 45 min). Inhibition of nitric oxide synthesis with the Nw-nitro-L
      arginine methyl ester (L-NAME, 10(-4) M) augmented the vasoconstriction induced
      by endothelin-1 in non-ischemic hearts, but not following ischemia. Similarly, L
      NAME increased the vasoconstriction induced by U46619 to a greater extent in non
      ischemic hearts than following ischemia. These results suggest that ischemia
      reperfusion inhibits nitric oxide production, causing an increased coronary
      response to endothelin-1 after brief ischemias. Longer ischemias may non
      specifically inhibit coronary vasoconstriction and reduce nitric oxide
      production.

PMID- 15733553
TI  - Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in
      rat detrusor muscle.
AB  - We have investigated the mechanism through which hydrogen sulfide (H2S)
      stimulates capsaicin-sensitive primary afferent neurons in the rat isolated
      urinary bladder. Sodium hydrogen sulfide (NaHS), a donor of H2S, produced
      concentration-dependent contractile responses (pEC50=3.5+/-0.1) that were
      unaffected by the transient receptor potential vanilloid receptor 1 (TRPV1)
      antagonist capsazepine (30 microM) and SB 366791 (10 microM) and by the N-type
      Ca2+ channel blocker omega-conotoxin GVIA (omega-CTX; 100 nM). In contrast, the
      unselective transient receptor potential (TRP) cation channels blocker ruthenium
      red (30 microM) almost abolished NaHS-induced contractions. Ruthenium red (30
      microM) greatly reduced capsaicin-induced contractions, whereas it did not
      attenuate the contractile response to neurokinin A. The putative TRPV1 receptor
      antagonist iodo-resiniferatoxin, from 100 nM upward, produced agonist responses
      per se, and could not be tested against NaHS. We conclude that H2S either acts at
      TRPV1 receptorial sites unblocked by capsazepine or SB 366791, or stimulates a
      still unidentified transient receptor potential-like channel co-expressed with
      TRPV1 on sensory neurons.

PMID- 15733554
TI  - Contrasting effects of tetraethylammonium and 4-aminopyridine on the
      gastrointestinal function of mice.
AB  - Many different K+ channels have been identified in the gastrointestinal tract,
      and the two classical K+ channel blockers, tetraethylammonium and 4
      aminopyridine, show different sensitivity for these channels. The aim of the
      present study was to compare the effects of tetraethylammonium and 4
      aminopyridine on the gastrointestinal function of mice. 4-Aminopyridine (5 mg/kg,
      p.o.) inhibited, but tetraethylammonium (40 mg/kg, p.o.) enhanced, the intestinal
      propulsion of a charcoal suspension in conscious mice. Studies in vitro showed
      that perfusion of 5 mM 4-aminopyridine increased the maximal contractile force
      and minimal relaxation force, and decreased the amplitude and frequency of the
      peristaltic contraction of the isolated duodenum. However, perfusion of 5 mM
      tetraethylammonium increased the maximal contractile force, the minimal
      relaxation force and the amplitude of the contraction. The effects of
      tetraethylammonium and 4-aminopyridine on the duodenal contraction could be
      abolished completely by application of 5 microM verapamil. Our results in vivo
      and in vitro showed that tetraethylammonium and 4-aminopyridine had contrasting
      effects on the gastrointestinal function of mice.

PMID- 15733555
TI  - The influence of hypothermia on P2 receptor-mediated responses of frog skeletal
      muscle.
AB  - The contractile responses of isolated Rana ridibunda frog sartorius muscle
      contractions evoked by electrical field stimulation (EFS) were studied at three
      temperature conditions of 17, 22 and 27 degrees C. Temperature-dependent increase
      of muscle contractility was found. ATP (10-100 microM) concentration dependently
      inhibited the electrical field stimulation-evoked contractions of sartorius
      muscle at all three temperatures; this effect was significantly more prominent at
      a temperature of 17 degrees C than at other two temperatures. Adenosine (100
      microM) also caused inhibition of electrical field stimulation-evoked
      contractions which was statistically identical at all three temperature
      conditions tested. A P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS, 10 microM) reduced the inhibitory effect of ATP at all
      three temperatures but did not affect inhibitory action of adenosine. In
      contrast, 8-(p-sulfophenyl)theophylline (8-SPT, 100 microM), a nonselective P1
      receptor antagonist, abolished inhibitory effects of adenosine at all three
      temperature conditions but did not antagonize inhibition caused by ATP. In
      electrophysiological experiments, ATP (100 microM) and adenosine (100 microM)
      temperature dependently reduced end-plate currents recorded in sartorius
      neuromuscular junction by voltage-clamp technique. The inhibitory effects of both
      agonists were enhanced with the decrease of temperature. 8-SPT (100 microM)
      abolished the inhibitory effect of adenosine but not ATP on end-plate currents.
      Suramin (100 microM), a nonselective P2 receptor antagonist, inhibited the action
      of ATP but not adenosine, while PPADS (10 microM) had no influence on the effects
      of either ATP or adenosine. It is concluded from this study that the
      effectiveness of P2 receptor-mediated inhibition of frog skeletal muscle
      contraction in contrast to that of adenosine is dependent on the temperature
      conditions.

PMID- 15733556
TI  - Effects of dietary baicalin supplementation on iron overload-induced mouse liver
      oxidative injury.
AB  - Iron overload is one of the most common metal related toxicity. Under this
      circumstance, excessive iron deposition in liver will lead to further injury such
      as hepatocellular necrosis, inflammation, fibrosis, and in some cases even to
      carcinoma. In this paper, the effect of a nature flavonoid, baicalin, on iron
      overload-induced mouse liver oxidative injury has been studied. It was found that
      when iron-dextran-induced iron overload, mice were fed baicalin-containing diet
      (0.25% and 1%) for 50 days, hepatic iron, liver-to-body weight ratio, and hepatic
      lipid peroxidation were dose-dependently decreased; while catalase activity,
      total antioxidant status, and serum iron content were dose dependently increased.
      The protective effect of baicalin on liver of iron overload mouse may due to both
      the antioxidant and iron chelation activities of baicalin. These data provide
      preliminary experimental support for baicalin as medicine for iron overload
      diseases.

PMID- 15733557
TI  - The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured
      human tracheal epithelial cells.
AB  - To examine the effects of lansoprazole, a proton pump inhibitor, on rhinovirus
      infection in airways, human tracheal epithelial cells were infected with a major
      subgroup of rhinoviruses, type 14 rhinovirus. Rhinovirus increased the mRNA
      expression of intercellular adhesion molecule-1 (ICAM-1) in the cells, the major
      rhinovirus receptor, and the content of the soluble form of ICAM-1 (sICAM-1) and
      cytokines in supernatants. Lansoprazole reduced supernatant titers and RNA of
      rhinovirus, the susceptibility to rhinovirus infection, the ICAM-1 mRNA
      production, the number and fluorescence intensity of acidic endosomes in the
      cells, and supernatants sICAM-1 and cytokine concentrations including interleukin
      1beta. Antibody to interleukin-1beta reduced baseline and rhinovirus-induced ICAM
      1 production. These results suggest that lansoprazole inhibits rhinovirus
      infection by reducing ICAM-1 via partly endogenous production of interleukin
      1beta, and by blocking the rhinovirus RNA entry into the endosomes. Lansoprazole
      may modulate airway inflammation by reducing the production of cytokines and ICAM
      1 in rhinovirus infection.

PMID- 15733559
TI  - Cholera and Shiga toxin B-subunits: thermodynamic and structural considerations
      for function and biomedical applications.
AB  - The B-subunits of cholera and Shiga toxins are functionally and structurally
      related proteins with different chain lengths and no sequence similarity. They
      are responsible for toxin binding to specific glycosphingolipid receptors and
      intracellular toxin trafficking. Indeed, it is clearly established that B
      subunits have the unique capacity of targeting the toxins to a poorly explored
      intracellular pathway, the retrograde route, allowing the transfer to the cytosol
      of the associated catalytic A-subunits, by retro-translocation from the
      endoplasmic reticulum. The B-subunits have also been used as vectors for antigen
      presentation in immunotherapeutic approaches. It is, however, not known if and
      how the B-subunits intervene in membrane translocation of the A-subunits and/or
      antigens to the cytosol. Therefore, it is important to characterise the driving
      force of pentamer formation, its conformational stability, and toxin-receptor
      interactions. This review summarises recent studies that have dealt with these
      topics.

PMID- 15733558
TI  - Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and
      increases insulin secretion in Zucker Diabetic Fatty rats and is associated with
      reduced plasma activity of dipeptidyl peptidase IV.
AB  - Sensory nerve desensitization by capsaicin has been shown to improve the diabetic
      condition in Zucker Diabetic Fatty rats. However, administration of capsaicin to
      adult rats is associated with an increased mortality. Therefore, in this
      experiment, we examined the influence of resiniferatoxin, a tolerable analogue of
      capsaicin suitable for in vivo use, on the diabetic condition of Zucker Diabetic
      Fatty rats. A single subcutaneous injection of resiniferatoxin (0.01 mg/kg) to
      these rats was tolerable, with no mortality. When administered to early diabetic
      rats at 15 weeks of age, the further deterioration of glucose homeostasis was
      prevented by resiniferatoxin. Further, when administered to overtly diabetic rats
      at 19 weeks of age, resiniferatoxin markedly improved glucose tolerance at two
      weeks after administration and this was accompanied by an increased insulin
      response to oral glucose as well as a reduction in the plasma levels of
      dipeptidyl peptidase IV. Therefore, resiniferatoxin is a safe alternative to
      capsaicin for further investigations of the role of the sensory nerves in
      experimental diabetes.

PMID- 15733560
TI  - Antioxidant enzyme activity and lipid peroxidation in liver and kidney of rats
      exposed to microcystin-LR administered intraperitoneally.
AB  - The effect of acute exposure of intraperitoneal injection of microcystin-LR
      (MCLR) on antioxidant enzymes and lipid peroxidation has been studied in liver
      and kidney of rats. Rats were treated with two doses, i.e. 100 and 150 microg of
      pure MCLR/kg body weight or saline solution. The enzyme activities of glutathione
      peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD) and
      catalase (CAT) in the liver were significantly decreased in MCLR-treated rats.
      The decrease of GR activity in the liver was 60%, followed by GSH-Px, SOD and
      CAT. Similarly, a decrease in the antioxidant enzymes was found in the kidney of
      MCLR-treated rats, such as GSH-Px (27-31%), GR (22%), SOD (42%) and CAT (25-28%).
      Concomitantly, significant increases in lipid peroxidation levels were recorded
      in liver (121 and 196% for 100 and 150 microg/kg, respectively) and kidney (48
      and 58% for 100 and 150 microg/kg, respectively) from MCLR-treated rats. In
      conclusion, acute exposure to MCLR results in a decrease in the antioxidant
      enzymes and an increase in lipid peroxidation in liver and kidney rats,
      suggesting the oxidative stress as an important role in the pathogenesis of MCLR
      induced toxicity. Antioxidant enzymes were significantly consumed in the liver
      and a minor decrease was found in kidney, confirming the organ-specific effects
      of MCLR.

PMID- 15733561
TI  - Identification and partial characterisation of hyaluronidases in Lonomia obliqua
      venom.
AB  - By studying Lonomia obliqua (caterpillar) venom we were able to detect a lytic
      activity on purified hyaluronic acid. The venom hydrolyses purified chondroitin
      sulphate, but was unable to degrade either heparan sulphate or dermatan sulphate.
      Moreover, through purified hyaluronic acid-degrading kinetic assays, we observed
      that this lytic activity was caused by a hydrolase rather than lyase enzyme. In
      addition, by using the Reissig colorimetric reaction, we detected this hyaluronic
      acid hydrolase action as a beta-endohexosaminidase enzyme originating terminal N
      acetylglucosamine residues rather than beta-endoglucuronidase, which may
      originate glucuronic acid residues. Zymogram analysis of the venom detected 49
      and 53 kDa molecules with hyaluronic acid lytic activity. An examination of these
      hyaluronic acid degrading activities as a function of pH showed that these
      hydrolases had no apparent activities at a pH below 5.0 and higher than 8.0 and
      displayed their optimal activities at pH ranging from 6.0 to 7.0. Finally,
      through a fluorescence reaction to hyaluronic acid and confocal microscopy, we
      confirmed this cleaving action upon hyaluronic acid organised on the
      extracellular matrix of the dermis of rabbit. The data provide experimental
      evidence of the presence of hyaluronidases in the L. obliqua venom, probably
      involved in the harmful effects of the venom.

PMID- 15733562
TI  - Purification and characterization of a hemorrhagic metalloproteinase from
      Bothrops lanceolatus (Fer-de-lance) snake venom.
AB  - Bothrops snake venoms contain metalloproteinases that contribute to the local
      effects seen after envenoming. In this work, a hemorrhagic metalloproteinase
      (BlaH1) was purified from the venom of the snake Bothrops lanceolatus by a
      combination of gel filtration, affinity (metal chelating) and hydrophobic
      interaction chromatographies. The hemorrhagin was homogeneous by SDS-PAGE and had
      a molecular mass of 28 kDa that was unaltered by treatment with beta
      mercaptoethanol. BlaH1 gave a single band in immunoelectrophoresis and
      immunoblotting using commercial bothropic antivenom. BlaH1 had hemorrhagic,
      caseinolytic, fibrinogenolytic, collagenolytic and elastinolytic activities, but
      no phospholipase A(2) activity. The hemorrhagic and caseinolytic activities were
      inhibited by EDTA, indicating that they were metal ion-dependent. In contrast,
      aprotinin, benzamidine and PMSF did not affect these activities. The caseinolytic
      activity of BlaH1 had a pH optimum of 8.0 and was stable in solution at up to 40
      degrees C; activity was completely lost at > or =70 degrees C. The hemorrhagic
      activity was neutralized by commercial bothropic antivenom. These properties
      suggest that this new hemorrhagin belongs to class P-I snake venom
      metalloproteinases.

PMID- 15733563
TI  - Variations in Loxosceles spider venom composition and toxicity contribute to the
      severity of envenomation.
AB  - Envenomation by Loxosceles spiders causes two main clinical manifestations:
      cutaneous and systemic loxoscelism. The factors contributing to the severity of
      loxoscelism are not fully understood. We have analysed biochemical and toxicity
      variations in venom of L. laeta and L. intermedia, with the aim to find a
      correlation with the seriousness of loxoscelism. Differences in expression of
      proteins, glycoproteins and sphingomyelinase activity were observed between venom
      from male and female spiders and between venom from the two species. These
      differences were reflected in the toxicity of the venoms including the capacity
      to induce complement-dependent haemolysis, dermonecrosis and lethality.
      Comparative analysis of gender and species, showed that these biological
      activities were more prominent in venom from female spiders, especially from L.
      laeta. Antiserum raised against venom from females L. laeta spiders had the
      highest efficacy in neutralizing venoms of males and females of both species.
      These results indicate that the severity of loxoscelism depends, at least
      partially, on the species and sex of the spider and suggest that for accidents
      involving L. laeta an specific serum therapy is necessary. Furthermore, it
      emphasizes the efficacy of the antiserum produced against L. laeta female venom
      in neutralizing Loxosceles venoms from different species and gender.

PMID- 15733564
TI  - Heteropoda toxin 2 is a gating modifier toxin specific for voltage-gated K+
      channels of the Kv4 family.
AB  - Kv4 voltage-gated K(+) channels are responsible for transient K(+) currents in
      the central nervous system and in the heart. HpTx2 is a peptide toxin that
      selectively inhibits these currents; making it a useful probe for understanding
      Kv4 channel structure and drug binding. Therefore, we developed a method to
      produce large amounts of recombinant HpTx2. Recombinant toxin inhibits all three
      Kv4 isoforms to the same degree; however, the voltage-dependence of inhibition is
      less apparent for Kv4.1 than for Kv4.3. Similarly, recombinant HpTx2(GS) effects
      gating characteristics of both channels, but Kv4.1 to a much lesser degree. The
      toxin lacks affinity for Kv1.4, Kv2.1, and Kv3.4. To locate the binding site, the
      amino acids linking the third and forth membrane spanning segments of Kv4.3 were
      replaced with analogous amino acids of Kv1.4. The chimeric K(+) channel was
      completely insensitive to block by rHpTx2, suggesting that its binding site is
      near the channel's voltage sensor. These data show that rHpTx2(GS) is a gating
      modifier toxin that binds to a site remote from the pore.

PMID- 15733565
TI  - Severe tongue necrosis associated with pine processionary moth (Thaumetopoea
      wilkinsoni) ingestion in three dogs.
AB  - The pine processionary moth (Thaumetopoea wilkinsoni) is an insect of medical
      significance in the eastern Mediterranean. This report describes three exposure
      cases in dogs due to ingestion of this moth's caterpillars in Israel. All three
      dogs were observed in direct contact with caterpillars or pinecones in infested
      gardens. The disease course and progression of signs were acute in all three
      cases, and included vomiting and severe tongue swelling. Physical examination
      findings included hyperthermia, tachypnoea, respiratory distress, cyanosis and
      tongue oedema, labial angioedema, ptyalism, bilateral submandibular
      lymphadenomegaly and conjunctivitis. Severe tongue necrosis and sloughing of its
      distal portion occurred 2-5 days after admission to the hospital. All dogs
      recovered and were discharged within 2-7 days of admission. Two staff members,
      attending one of the dogs, experienced an itchy rash and wheals on their arms,
      wrists and necks. To the best of our knowledge, this should be the first report
      of severe oral lesions and tongue necrosis due to contact with T. wilkinsoni
      caterpillars.

PMID- 15733566
TI  - Analysis of the toxic potential of venom from Loxosceles adelaida, a Brazilian
      brown spider from karstic areas.
AB  - Loxosceles adelaida spiders (Araneae, Sicariidae) are found near and inside the
      caves in the Parque Estadual Turistico do Alto Ribeira (PETAR), Sao Paulo,
      Brazil, which are visited by thousands of tourists every year. Several Loxosceles
      species are a public health problem in many regions of the world, by causing
      severe dermonecrosis and/or complement dependent haemolysis upon envenomation.
      The aim of this study was to characterize the biochemical and biological
      properties of L. adelaida venom and evaluate the toxic potential of envenomation
      by this non-synanthropic Loxosceles species. The biological activities of the L.
      adelaida venom was compared to that of Loxosceles gaucho, a synanthropic species
      of medical importance in Brazil. L. adelaida venom showed a similar potential to
      induce haemolysis, dermonecrosis and lethality as L. gaucho venom. L. adelaida
      crude venom was purified, yielding a 31 kDa component endowed with haemolytic and
      dermonecrotic activities. In conclusion, we show here that the troglophile
      Loxosceles species, L. adelaida, commonly found in the complex of caves from
      PETAR, is potentially able to cause envenomation with the same gravity of those
      produced by synanthropic species.

PMID- 15733567
TI  - Effects of Lantana camara (Verbenaceae) on general reproductive performance and
      teratology in rats.
AB  - Lantana camara L. (Verbenaceae) possesses several medicinal properties and it is
      used in folk medicine with antipyretic, antimicrobial and antimutagenic
      properties. This plant is one of the 10 most noxious weeds in the world. Lantana
      poisoning have caused severe economic losses and was the major cause of livestock
      mortality and morbidity. In this article we report the effects of hydroalcoholic
      extract from Lantana camara var. aculeata leaves on fertility, general
      reproductive performance and teratology in the rat. The data showed that the
      extract interfered in the frequency of fetal skeleton anomalies from dams treated
      with the extract and induced embryotoxicity as indicated by post-implantation
      loss, without any signs of maternal toxicity. The other parameters evaluated did
      not suggest modifications.

PMID- 15733568
TI  - The improvement of the therapeutic anti-Lachesis muta serum production in horses.
AB  - The main features associated with pit viper envenomations include the intense
      local lesions such as oedema, necrosis, acute renal failure and other effects.
      The severity of these reactions to snakebite depends on the degree of
      envenomation. Lachesis muta venom (LMV) has weak lethal activity, but due to the
      large amount often inoculated, the effects are extremely severe and demand anti
      venom with a high neutralizing capacity. LMV had the lowest neutralizing antibody
      induction capacity in horses when compared with that of other venoms. For
      example, Bothrops anti-venom serum neutralizes 180 times the equivalent LD(50) to
      Bothrops venom; Crotalus anti-venom neutralizes 250 LD(50) of this venom, while
      Lachesis anti-venom neutralizes only five LD(50) of the Lachesis toxins. To
      examine the reasons for this low antibody induction, the H(GP) mouse line,
      genetically selected for high antibody production received, at different times
      during immunization with sheep erythrocytes (SE), whole LMV and isolated venom
      fractions I-VI eluted by gel-filtration chromatography on Superdex75. The
      specific antibody responsiveness showed a partial, but significant suppression of
      the anti-SE antibody responses during the kinetics of the primary and even the
      secondary immunizations, after 50-100 microg of fractions IV and V administration
      72-48 h before the first antigen injections. Fraction IV was then applied in a
      Superose 12 column and three samples were obtained. The peak IVA containing a
      component of Mr 27 kDa was liable with the immunosuppressive effect as made
      evident by its effect on the H mice anti-SE responses. Horses receiving the LMV
      exempt of fractions IV and V produce highly significant anti-Lachesis sera with a
      45 LD(50) neutralizing activity, providing, for the first time, an efficient
      specific therapeutic heterologous serum for human use.

PMID- 15733569
TI  - Mitochondrial DNA D-loop as a new target of Saporin 6 nuclease activity.
AB  - The single-chain ribosome-inactivating proteins (RIPs) from plant origin,
      including Saporin 6 from the seeds of Saponaria officinalis, are ribotoxins known
      to act as N-glycosidases which depurinate the conserved alpha sarcin loop of
      large rRNAs. As a consequence, the eukaryotic ribosomes become inactivated,
      thereby arresting the protein synthesis at the elongation step. RIPs are
      currently under study as antiviral and antiproliferative agents. Additional in
      vitro activities of RIPs against either RNA or DNA have been recently described.
      A specific nuclease activity on plasmidic DNA was demonstrated by either purified
      or bacterial-recombinant molecules. We report here that human mitochondrial DNA
      (mtDNA) is a new specific target of Saporin 6 nuclease activity. A unique site of
      cleavage has been identified and mapped within the most variable part of the D
      loop region of the covalently closed circular mtDNA molecule.

PMID- 15733570
TI  - Sequence diversity of T-superfamily conotoxins from Conus marmoreus.
AB  - Remarkable sequence diversity of T-superfamily conotoxins was found in a mollusk
      hunting cone snail Conus marmoreus. The sequence of mr5a purified from the snail
      venom was determined, while six other sequences of Mr5.1a, Mr5.1b, Mr5.2, Mr5.3,
      Mr5.4a, and Mr5.4b were deduced from their corresponding cDNA cloned by RACE
      approach. mr5a of 10 amino acid residues is one of the shortest T-superfamily
      conotoxins ever found. They all share a typical (-CC-CC-) Cys pattern, a
      conserved signal peptide and a long 3'-untranslated region. A consensus Glu
      residue is preceded by the second two adjacent cysteines in all these toxins
      except in mr5a, whereas Mr5.1a, Mr5.1b, Mr5.4a and Mr5.4b are abundant in Trp
      residues. The identification of these highly divergent T-superfamily conotoxins
      will facilitate the understanding the relationship of their structure and
      function.

PMID- 15733571
TI  - Enzymatic characterization, antigenic cross-reactivity and neutralization of
      dermonecrotic activity of five Loxosceles spider venoms of medical importance in
      the Americas.
AB  - Loxosceles spiders have a wide distribution in the temperate and tropical regions
      of the world. Loxoscelism is characterized by necrotic skin ulceration at the
      bite site and, less commonly, a systemic illness that may be fatal. The purpose
      of this study was to characterize and compare aspects of the major medically
      important Loxosceles spider venoms in a standardized manner, particularly
      considering their neutralization by two Brazilian antivenoms. By SDS-PAGE (12%
      acrylamide), Loxosceles deserta, Loxosceles gaucho, Loxosceles intermedia,
      Loxosceles laeta and Loxosceles reclusa venoms had similar electrophoretic
      profiles, with the major protein bands of 32-35 kDa. All venoms exhibited
      gelatinolytic, caseinolytic and fibrinogenolytic activities in vitro with a large
      array of proteases, mainly between 18.1 and 31.8 kDa. Most of these enzymes were
      metalloproteases as this activity was abolished by 1,10-phenanthroline.
      Hyaluronidase activity was detected in a protein band of approximately 44 kDa in
      all venoms. Sphingomyelinase activity was demonstrated in all five venoms.
      Antigenic cross-reactivity, by Western blotting, was also observed among all
      venoms studied using commercial equine antivenoms produced in Brazil (Institute
      Butantan and CPPI). These antivenoms recognized mainly components between 25 and
      40 kDa in all venoms with several minor components of >89 kDa. Strong cross
      reactivity was also seen among all venoms through the ELISA technique (titre
      range: 64,000-512,000). All venoms (5 microg doses) induced a similar local
      reaction when injected intradermally into the flank of rabbits, demonstrating
      dermonecrosis, hemorrhage, vasoconstriction, edema, and erythema. However, no
      reaction was observed when each venom was pre-incubated (1 h, 37 degrees C) with
      Brazilian commercial sera prior to injection. The antivenoms also abolished the
      sphingomyelinase activity in vitro, suggesting the venoms of the major medically
      important Loxosceles spider species have generally similar toxic and enzymatic
      characteristics. Thus, as Brazilian commercial antivenoms are able to neutralize
      the dermonecrosis induced by Loxosceles venoms of diverse geographical origin,
      clinical studies should be undertaken on the potential for a single global
      Loxosceles antivenom.

PMID- 15733572
TI  - The depressant scorpion neurotoxin LqqIT2 selectively modulates the insect
      voltage-gated sodium channel.
AB  - LqqIT2 is a depressant neurotoxin present in the venom of the Leiurus
      quinquestriatus quinquestriatus scorpion, one of the world's most dangerous
      scorpions endemic to dry habitats in Africa and Asia. In order to determine its
      efficacy, potency and selectivity, LqqIT2 was subjected for the first time to an
      electrophysiological and pharmacological comparison between two different cloned
      sodium channels expressed in Xenopus laevis oocytes. Aside from typical beta
      toxin effects, LqqIT2 also affected the inactivation process and ion selectivity
      of the insect voltage-gated sodium channel. The most interesting feature of
      LqqIT2 is its total insect-selectivity. At a concentration of 1 microM, the
      insect-voltage-gated sodium channel, para, was profoundly modulated while its
      mammalian counterpart, the rat brain Na(v)1.2 channel, was not affected. This
      trait offers excellent prospects for the development of novel insecticides.

PMID- 15733573
TI  - Intracellular and dissolved microcystin in reservoirs of the river Segura basin,
      Murcia, SE Spain.
AB  - The seasonal sampling of irrigation or drinking water reservoirs in the province
      of Murcia (SE Spain) in the hydrological year 2000-2001 revealed the presence of
      intracellular microcystins in the benthic cyanophyte communities throughout the
      year. The total microcystin levels, as measured by HPLC, were relatively high but
      lower than others published for planktonic communities of the European continent
      or certain African countries. The diversity of forms was also very high and
      comparable to those found for other European countries. The concentrations of
      microcystins dissolved in the water were always below limits recommended by the
      WHO for drinking water and, during most of the year, undetectable by
      immunological methods. We discuss the need for setting up a control network for
      detecting benthic cyanobacteria growth to prevent long-term undesirable effects
      in the human population in small towns (through drinking water or the consumption
      of vegetables) and in wild animals. In the particular case of the Iberian
      Peninsula, a joint strategy between Portugal and Spain is recommendable.

PMID- 15733574
TI  - Cardiovascular effects and lethality of venom from nematocysts of the box
      jellyfish Chiropsalmus quadrigatus (Habu-kurage) in anaesthetized rats.
AB  - Haemodynamic effects of saline-extracted venom from nematocysts isolated from
      Chiropsalmus quadrigatus (Habu-kurage) were studied in anaesthetized rats.
      Intravenous administration of venom (0.2-5 microg protein/kg) produced
      immediately dose-dependent hypertension and bradycardia. Femoral blood flow
      transiently increased but calculated femoral vascular conductance decreased.
      Changes caused by 1 microg/kg of venom were reproducible, and were not affected
      by prazosin, atropine or BQ123 (ET(A) receptor antagonist) but were significantly
      attenuated by nicardipine. At doses over 2 microg/kg, hypotension and a decrease
      in pulse pressure were observed subsequent to transient hypertension. In 5 of 8
      rats received 5 microg/kg venom and 6 of 6 rats at 10 microg/kg, death due to
      irreversible cardiac arrest occurred within 30 min after intravenous injection.
      However, during nicardipine infusion, venom (10 microg/kg) exerted only modest
      effects and the rats survived. Heating venom (50 degrees C for 10 min) before
      injection practically abolished the haemodynamic effects of 10 microg/kg venom,
      indicating its thermolability. Data show that C. quadrigatus venom has both
      vasoconstrictor and cardiodepressive effects in rats, and suggest that a calcium
      channel blocker can protect against the cardiovascular and lethal effects of the
      venom.

PMID- 15733575
TI  - Duvernoy's gland secretion of Philodryas patagoniensis from the northeast of
      Argentina: its effects on blood coagulation.
AB  - Duvernoy's gland secretion of Philodryas patagoniensis exhibits high hemorrhagic
      activity, containing enzymes that are able to degrade the vascular wall. In this
      work we aim to determine if the secretion can also affect the hemostatic system
      by causing changes in blood coagulation. Procoagulant and coagulant activities
      were evaluated on plasma and fibrinogen, respectively. The delay in the thrombin
      clotting time of fibrinogen previously incubated with the secretion was also
      determined. Specific hydrolysis of fibrinogen and fibrin incubated with the
      secretion at different time intervals was shown by electrophoresis on
      polyacrylamide gel. To determine the structural characteristics of the enzymes
      degrading fibrinogen and fibrin, secretion were incubated in the presence of 45
      mM Na(2)EDTA, 40 mM Benzamidine, and/or 2 mM PMSF before the incubation with
      fibrinogen or fibrin, respectively. The effect in vivo was investigated in adult
      male rats injected with different dose of secretion, aliquots of blood were
      withdrawn at different time intervals, and the fibrinogen concentration was
      determined. Duvernoy's gland secretion of P. patagoniensis did not clot plasma or
      fibrinogen. It exhibited a potent fibrinogenolytic activity degrading the Aalpha
      chain faster than the Bbeta-chain, whereas gamma-chain was resistant. This latter
      corresponded with a strong delay in the thrombin clotting time of fibrinogen (4
      mg/ml) pre-incubated with the secretion, being 9.53 microg the amount of protein
      from Duvernoy's gland secretion that increased the thrombin clotting time from 20
      to 60 s. In vivo, the loss of rat plasma fibrinogen was proportional to the
      amount of secretion injected. The secretion also hydrolyzed fibrin degrading the
      alpha-monomer. Inhibition studies with Na(2)EDTA, Benzamidine, and/or PMSF showed
      that metalloproteinases and serinoproteinases are the main enzymes responsible
      for the hydrolyzing activity on fibrinogen and fibrin. All these results
      demonstrate that Duvernoy's gland secretion of P. patagoniensis possesses enzymes
      able to hydrolyze plasma components playing a relevant role in the blood
      coagulation. These hydrolyzing activities and those acting on the wall of blood
      vessels let the secretion exhibit a high hemorrhagic activity, which may result
      in permanent sequelae or even cause the death of the victims bitten by this
      colubrid snake.

PMID- 15733576
TI  - Cloning and expression of a novel cDNA encoding a mannose-binding lectin from
      Dendrobium officinale.
AB  - Using RNA extracted from Dendrobium officinale young leaves and primers designed
      according to the conservative regions of orchidaceae lectins, the full-length
      cDNA of Dendrobium officinale agglutinin2 (DOA2) was cloned by rapid
      amplification of cDNA ends (RACE). The full-length cDNA of doa2 was 777 bp and
      contained a 513 bp open reading frame (ORF) encoding a lectin precursor of 170
      amino acids. Through comparative analysis of doa2 gene and its deduced amino acid
      sequence with those of other orchidaceae species and Amaryllidaceae species, it
      was found that DOA2 had many common characters of mannose-binding lectin
      superfamily including three mannose-binding sites. Semi-Quantitative RT-PCR
      analysis revealed that doa2 mRNA expression was detected in all tested tissues
      including root, stem and leaf, however, the expression was higher in stem, and
      lower in leaf. As the doa2 mRNA was detected in all the tested plant tissues, the
      doa2 was considered to be a constitutively expressed gene. The recombinant
      protein was expressed in E. coli and purified. Anti-fungal assay showed that DOA2
      has anti-fungal activity towards Gibberella zeae. To our knowledge, this is the
      first report on cDNA cloning of mannose binding lectin from Dendrobium
      officinale.

PMID- 15733577
TI  - Vascular dopplers: a new way of recording cardiac parameters in envenomed
      organisms.
AB  - Measuring cardiac activity in experimental animals for research purposes has
      great relevance and obvious implications for investigating venom actions and
      toxicity. Previous techniques have been confined to vertebrate models as
      traditional heart recording apparatuses require a closed vascular system to be
      effective. A new technique utilizing a Vascular Doppler placed external to the
      cardiac muscle was trialled in order to record previously undocumented
      invertebrate heart activity of envenomed animals. Combined with Avisoft sound
      collection software, this technique was found to be successful in recording
      cardiac parameters such as heart rate and extent of contraction in an
      invertebrate model. This method is advantageous as it is not only inexpensive and
      easily portable but allows for specific venom actions to be investigated in a
      wider variety of previously unreportable, but ecologically significant animals.

PMID- 15733578
TI  - Microcalorimetry is a sensitive method for studying the effect of nucleotide
      mutation on promoter activity.
AB  - Microcalorimetric method was successfully used to study the effect of nucleotide
      mutations on promoter activity and identify the important nucleotide necessary
      for the promoter function in Escherichia coli. The thermokinetic parameters, such
      as k, I and IC(50), were calculated from the metabolic power-time curves obtained
      by microcalorimetric measurement using the TAM air Isothermal Microcalorimeter
      (manufactured by Thermometric AB company of Sweden). Analysis of these data
      revealed that different nucleotide mutations in -10 box sequence of RM07 fragment
      had different effect on the promoter activity. Our research also suggest that the
      microcalorimetric method is a very sensitive and easily performed method for
      investigation of promoter mutation.

PMID- 15733579
TI  - A simultaneous electrochemical impedance and quartz crystal microbalance study on
      antihuman immunoglobulin G adsorption and human immunoglobulin G reaction.
AB  - The quartz crystal microbalance (QCM), in combination with electrochemical
      impedance spectroscopy (EIS), has been utilized to monitor in situ antihuman IgG
      (hIgG) adsorption on bare poly(o-phenylenediamine) (PPD)- and 1-dodecanethiol
      (C12SH)-modified Au electrodes and succeeding human IgG reaction, respectively.
      The resonant frequency (f) and the motional resistance (R(1)) of the
      piezoelectric quartz crystal (PQC) as well as electrochemical impedance (EI)
      parameters were measured and discussed. The standard heterogeneous rate constants
      of the ferricyanide/ferrocyanide couple before and after the antibody adsorption
      and antibody-antigen reactions were determined. The results show that the amount
      for antibody adsorption was the greatest on the most hydrophobic (1-dodecanethiol
      modified) surface, while the antibody bioactivity was almost identical on the
      three kinds of surfaces. Two parameters simultaneously obtained, Deltaf and
      DeltaC(s) (interfacial capacitance), have been used for the first time to
      estimate both the association constant of the immunoreaction and the valence of
      antigen with satisfactory results. The proposed method may find wide application
      in interfacial biochemistry studies for its advantages in providing real-time
      multidimensional piezoelectric and electrochemical impedance information.

PMID- 15733580
TI  - An easy approach for the purification of native TFIIH.
AB  - Transcriptional regulation depends on the appropriate set of positive and
      negative regulating signals in order to provide the correct gene expression. In
      vitro studies in eukaryotic gene expression over the last few years have provided
      a wealth of information about new factors involved in the regulation of genes.
      However, the dissection of this mechanism requires the addition of well
      characterized general transcription factors; with the exception of TFIID and
      TFIIH, all others can easily be expressed in a recombinant form. Here we provide
      a simple methodology to obtain partially purified transcriptionally active TFIIH
      free from other general transcription factors and active in transcription.

PMID- 15733581
TI  - Preparation of polyvinyl alcohol-polyacrylamide composite polymer membrane by
      gamma-irradiation for entrapment of urease.
AB  - Composite polymer membrane of polyvinyl alcohol (PVA) and acrylamide was prepared
      on cheesecloth support by gamma-irradiation induced free radical polymerization.
      The enzyme urease was entrapped in the membrane during polymerization and was
      cross-linked within the matrix using glutaraldehyde. The membranes could be
      reused a number of times without significant loss of urease activity.

PMID- 15733582
TI  - Direct enantiomeric resolutions of chiral triazole pesticides by high-performance
      liquid chromatography.
AB  - Cellulose-tris (3,5-dimethylphenylcarbamate; CDMPC) was synthesized and coated on
      aminopropylsilica to prepare chiral stationary phase (CSP). Normal-phase high
      performance liquid chromatography (HPLC) methods for the resolutions of five
      chiral triazole pesticides, diniconazole, tebuconazole, hexaconazole, triadimefon
      and flutriafol, on the CSP were developed. Several operating parameters such as
      mobile phase composition, modifier and column temperature were studied for the
      optimization of the resolutions. Better separations were achieved using 2% iso
      butanol for diniconazole, 2% ethanol for tebuconazole, 2% iso-propanol for
      hexaconazole, 1% n-butanol for triadimefon and 2% n-propanol for flutriafol as
      modifiers in n-hexane at 0 degrees C with the resolution factors (Rs) of 1.62,
      1.66, 2.46, 1.68 and 1.98, respectively. Low temperature was better for the
      resolutions. Validation of the methods included linearity and precision.

PMID- 15733583
TI  - Growth of human stem cell-derived neurons on solid three-dimensional polymers.
AB  - Understanding neural differentiation and the development of complex neurite
      networks in three-dimensional matrices is critical for neural tissue engineering
      in vitro. In this study we describe for the first time the growth of human stem
      cell-derived neurons on solid polystyrene matrices coated with bioactive
      molecules. Highly porous foams were prepared from poly(styrene/divinylbenzene)
      using a high internal phase emulsion (HIPE) as a template to create the porous
      structure. The resulting polyHIPE matrices were readily coated with aqueous-based
      solutions including poly-d-lysine and laminin. Human neurons adhered well to poly
      d-lysine coated surfaces and extended neural processes, however, neurite
      outgrowth was particularly enhanced when polymers also received a coating of
      laminin. These data clearly demonstrate the potential use of solid polystyrene
      scaffolds to create three-dimensional environments for cell growth and
      differentiation. We propose that these robust and stable matrices can be
      conveniently and routinely used in the tissue culture laboratory to study the
      behaviour of cells grown in three-dimensions.

PMID- 15733584
TI  - Real-time quantitative PCR assay for analysis of platelet glycoprotein IIIa gene
      expression.
AB  - A quantitative detection assay for analysis of platelet glycoprotein GPIIIa gene
      expression is presented. The assay uses two fluorescently labeled TaqMan MGB
      probes to detect the polymorphic site in GPIIIa nucleotide sequence, leading to
      antigens HPA-1a and HPA-1b. In order to avoid the influence of DNA contamination
      on RNA quantification, a forward primer was constructed to span an exon-exon
      junction. The assay is therefore applicable to expression studies also in samples
      containing only a small amount of contaminating DNA. To standardize the amount of
      sample cDNA added to the reaction, amplification of endogenous control 18SrRNA
      was included in a separate well. The amplification validation experiment showed a
      high real-time PCR efficiency for HPA-1a, HPA-1b and 18SrRNA. Relative
      quantification was therefore performed using the comparative C(T) method. The
      assay was optimized on a reversely transcribed total RNA from platelets, and the
      specificity rate was determined by sequencing. The amount of cDNA at which
      amplification was still clearly detectable was 5 ng. This newly developed real
      time quantitative PCR assay is a sensitive, reproducible and reliable method. It
      is suitable for studying different stages of megakaryopoiesis, monitoring
      molecular alteration in defective platelets and determining differences in the
      GPIIIa expression level between normal and pathological megakaryocytic
      differentiation pathways.

PMID- 15733585
TI  - A new PCR-based approach for the preparation of RNA probe.
AB  - A number of PCR-based in situ hybridization (ISH) techniques have been reported
      to facilitate the procedure. However, those techniques require additional gene
      specific primers with RNA polymerase binding site. We developed a new PCR-based
      ISH technique without extra gene-specific primers. We amplified gene specific PCR
      products with regular gene-specific primer pairs. Special linker, including T7
      RNA polymerase binding site, was adapted to amplified PCR products. Secondary PCR
      was performed with T7 primer, and forward or reverse primer, used for the first
      PCR to prepare template DNA for RNA transcription. We were able to generate sense
      and anti-sense probes for ISH in a day. Recently, real-time PCR and ISH are
      required to validate microarray results quantitatively and qualitatively. This
      technique can be expected to facilitate the high-throughput validation of
      transcripts detected by microarrays.

PMID- 15733586
TI  - Current challenges in diagnosis of acute otitis media.
AB  - Diagnosis of acute otitis media is difficult: circumstances and equipment for
      diagnosis are often compromised, the child may be uncooperative, signs and
      symptoms of acute otitis media and those of the common cold are mostly the same,
      and parents appear to have strong opinions concerning correct diagnosis and
      treatment. Many clinicians have received inadequate pre- and postgraduate
      education about diagnosis. On the other hand, they are aware of the worldwide
      problem of antimicrobial resistance resulting from antibiotics unwisely
      prescribed for viral infections. We performed a systematic search to summarize
      what is known about diagnosis of acute otitis media and suggest ways to improve
      one's diagnostic skills. With the combination of appropriate and well-maintained
      diagnostic equipment for tympanometry and pneumatic otoscopy, strict diagnostic
      criteria, and open communication with each child's parents it is possible to
      increase accuracy in acute otitis media diagnosis. Recent public health campaigns
      both among clinicians and parents, plus increased knowledge of diagnostics reveal
      the possibility of significantly decreasing the number of acute otitis media
      diagnoses in children which will lead to reduced prescription of antibiotics.

PMID- 15733587
TI  - Cult of St. Blasius, patron saint of throat sufferers and of otolaryngologists,
      in Croatia.
AB  - In the introductory part presented is a short hagiography of St. Blasius, and the
      legend of miraculous healing of a child in whose throat a bone had stuck,
      threatening to choke the child. Thanks to that legend, St. Blasius has become the
      traditional patron of the laryngeal diseases, and, since recently, the patron of
      the otolaryngologists, too. The second part of the paper is dedicated to the cult
      of St. Blasius, which is present in Croatia since the 10th century until present.
      Venerated all over the country, St. Blasius has been "elected" the heavenly
      protector of 10 parish communities, as well as of the city and the dioceses of
      Dubrovnik. Beside pilgrimage and prayers, among many traditional forms of folk
      piety, a ritual called "grlicenje" has been preserved-a curative and preventive
      blessing of the throat with crossed candles on the Saint's Day. In more recent
      times, the same day has been remembered among Croatian otolaryngologists and the
      societies of laryngectomized persons, who chose St. Blasius for their patron,
      too.

PMID- 15733588
TI  - Microdebrider-assisted supraglottoplasty.
AB  - OBJECTIVE: Although laryngomalacia is a common cause for infantile stridor, few
      patients eventually go on to require surgical intervention. When surgery is
      required, the location of tissue excised may vary depending on the endoscopic
      findings, but only two methods of tissue excision are described-cold knife
      excision and carbon dioxide laser. We present our experience of using the
      microdebrider to excise tissue during supraglottoplasty. METHODS: Over the last
      12 months, patients were identified who had undergone supraglottoplasty, and
      their final outcomes with regards to resolution of stridor, cor pulmonale, and/or
      failure to thrive were assessed. A description of the indications for
      supraglottoplasty and the actual technique utilizing the microdebrider is
      included. RESULTS: Five patients were identified as having undergone a
      microdebrider-assisted supraglottoplasty. All five had resolution of their
      stridor following surgery. No new complications such as aspiration or
      supraglottic stenosis were identified. No revision surgeries were required. The
      microdebrider was used to trim the aryepiglottic folds and/or redundant arytenoid
      mucosa in all cases. CONCLUSIONS: The microdebrider appears to be a safe and
      effective tool to remove redundant tissue during supraglottoplasty.

PMID- 15733589
TI  - Cephalometric assessment of the mandibular growth pattern in mouth-breathing
      children.
AB  - OBJECTIVE: At the present time, it is generally accepted that chronic mouth
      breathing influences craniofacial growth and development. The objective of this
      study was to determine the position of the jaw, its growth direction and
      morphology, and the facial proportions of children with two different etiological
      factors of mouth breathing, at different age groups. MATERIALS AND METHODS: Four
      groups of mouth breathing children were analyzed by cephalometry. Two groups,
      ages ranging from 3 to 6 and 7 to 10 years, with respiratory obstruction due to
      isolated adenoid hypertrophy (AH), and two groups, ages ranging from 3 to 6 and 7
      to 10 years, due to adenotonsillar hypertrophy (ATH). RESULTS: No significant
      differences were observed between mouth breathing children caused either by AH or
      by ATH in any of the age groups. Only the linear Ar-Go measurement was
      significantly larger in children with ATH with 7 years or more. CONCLUSIONS: The
      results suggest that the influence of mouth breathing on mandibular growth is
      poorly related to the etiological factors analyzed. The single difference
      observed was the lower posterior facial height in children of 7 years of age or
      more, which was higher in those with ATH than in those with AH.

PMID- 15733590
TI  - Three-dimensional CT angiography imaging of vascular tumors of the head and neck.
AB  - OBJECTIVE: To evaluate the utility of three-dimensional (3D) computerized
      tomography angiography (CTA) in head and neck vascular anomalies. DESIGN:
      Prospective case series. METHODS: A consecutive series of cases of patients with
      distinct types of vascular anomalies (i.e. hemangioma, arteriovenous
      malformation, venous malformation and lymphatic malformation) were obtained
      through CT multislice scanner and analyzed with Vitrea 2 software (Vital Images
      Inc., Plymouth, MN). RESULTS: CTA was safe and successful in describing 3D
      vascular anatomy of a variety of vascular lesions. CONCLUSIONS: Three-dimensional
      CTA allows detailed description of vascular lesions of the head and neck and
      offers another effective means of imaging these complex lesions.

PMID- 15733591
TI  - Is there any association between consanguinity and hearing loss.
AB  - BACKGROUND: Hearing loss (HL) and its complications appear to be increasingly
      common in developing countries. Previous studies have supported the association
      between hearing loss and consanguinity. OBJECTIVE: The aim of the present study
      was to determine the frequency of hearing loss and its association with
      consanguinity among Qatari population. In addition, correlation between hearing
      loss and Rhesus (Rh) blood groups has been investigated. DESIGN: This is a cross
      sectional study. SETTING: The study conducted at the Hamad General Hospital,
      Hamad Medical Corporation. SUBJECTS: Total sample of 2800 infants screened and
      2277 subjects were eligible to be included in the study. METHODS: The neonatal
      screening for hearing loss was conducted from January 2003 to November 2003 among
      all the 2800 infants born during that period. Some of them were admitted to
      neonatal intensive care unit (NICU). The hearing loss was screened using
      otoacoustic emission (Garson Stadler Incorporation, GSI-70), auditory brain stem
      responses (ABR) and tympanogram. RESULTS: Out of 2277 infant screened, the
      prevalence of hearing loss was (119/2277) 5.2%. The prevalence of HL was more
      common in boys (2.7%) than in girls (2.5%). We did not find any statistical
      significance differences between genders with the respect of HL. Parental
      consanguinity was more common among HL cases compared with non-HL 60.5% versus
      25.3% (p < 0.0001). Family history of hearing loss did not show any differences
      between the two groups. 4.2% versus 4.3%. Risk factors like caesarean section,
      prenatal smoking and prenatal high blood pressure did not show any significant
      differences between the two groups. However, admission to NICU is associated with
      increase prevalence of HL 8.4% versus 4.4% (p = 0.043). The present study
      revealed that strong correlation between hearing loss, consanguineous (r = 0.217,
      p < 0.01), father education level illiterate (r = 0.293, p < 0.01), mothers
      consanguineous (r = 0.206, p < 0.01), mothers educational level illiterate (r =
      0.228, p < 0.01), mother blood group positive (r = 0.476, p < 0.01), family
      history of HL among first or second degree of relatives (r = 0.620, p < 0.01) and
      father hypertension (r = 0.570, p < 0.01). Furthermore, a significant correlation
      between hearing loss and Rh blood groups has been discovered. CONCLUSION: The
      present study was directed at determining the prevalence and risk factors of HL
      in the infant population of Qatar. The data revealed that parental consanguinity
      was more common among hearing loss cases. There is a strong correlation between
      hearing loss and baby's age.

PMID- 15733592
TI  - Circumferential trachea reconstruction with a prefabricated axial bio-synthetic
      flap: experimental study.
AB  - OBJECTIVE: The ideal method, in reconstruction of circumferential tracheal
      defects more than 50% of the total tracheal length, is still a question. Current
      methods lack either in epithelial lining or in skeletal framework. In this study,
      we designed an axial biosynthetic prefabricated flap to reconstruct the
      circumferential tracheal defects in rabbits. METHODS: Ten rabbits are used. The
      inner mucosal lining is substituted by hairless epithelium obtained from proximal
      ear. The tracheal cartilage is substituted by polypropylene mesh and the tracheal
      adventitia is substituted by lateral thoracic fascia as a vascular supply. The
      study is designed in three stages. Stage 1: Hairless epithelial graft is obtained
      by secondary healing of a full thickness skin defect in ear. Stage 2: Epithelial
      graft, polypropylene mesh and lateral thoracic fascia are tubed around a silicone
      catheter. This structure is dissected through its pedicle (lateral thoracic
      vessels and fascia) to the axilla and mobilized. The prefabricated neotrachea is
      carried on its pedicle to the cervical area through a subcutaneous tunnel formed
      superficial to the sternum and left there for 2 weeks. Stage 3: The silicone
      catheter is taken out and prefabricated neotrachea is adapted to the defect
      formed in native trachea and anastomized. Later the animals are evaluated for 4
      weeks. The patency of the lumen, the viability of the epithelial graft and
      fascia, airtightness of the anastomoses and other features of the reconstruction
      are evaluated by radiological, macroscopical and histological examinations.
      RESULTS: Survival at 4 weeks was 70%. All of the prefabricated neotracheas and
      epithelial grafts were viable. The rigidities, longitudinal elasticities,
      diameters and wall thickness were similar to native tracheas. Occlusion of lumen
      is encountered only in one animal. There was no hair growth from the epithelial
      lining. CONCLUSION: The study defines a new method of circular tracheal
      reconstruction with successful substitution of inner lining, skeletal framework
      and vascular supply.

PMID- 15733593
TI  - Search for Herpesvirus 1 and 2 by in situ hybridization in tonsils and adenoids.
AB  - OBJECTIVE: Herpes simplex virus (HSV) has been described as cause of acute
      tonsillitis. It has also been found in nasopharyngeal florid lymphoid infiltrate,
      mostly composed of CD4+, CD56+ T-cells, simulating lymphoma. In spite of its
      widespread prevalence in latent form, to the best of our knowledge no study is
      available on in situ detection of HSV in chronically hyperplastic nasopharyngeal
      lymphoid tissue. The purpose of the present study was to search for the presence
      of HSV 1 and 2 in 21 adenoids and 15 tonsils from children (2-12 years of age) in
      which these organs had been surgically removed due to hypertrophy. METHODS:
      Paraffin wax-embedded sections from the 36 cases were submitted to the in situ
      hybridization technique, using the biotinilated probe to Herpes simplex virus 1
      and 2 (Pan Path, Amsterdam) and the Rembrandt Universal DISH & HRP Detection Kit
      (Pan Path, Amsterdam). Positive control consisted of a previously tested Herpes
      infected lung. RESULTS: In none of the 36 cases studied were positive nuclei
      detected in adenoid and tonsils, either in lymphoid, in stroma or in epithelial
      cells, as those seen in the positive control. CONCLUSION: HSV does not seem to be
      implied in tonsil or adenoid chronic lymphoid hyperplasia. These organs do not
      seem to harbor the virus latently, or the amount of virus is too low to be
      detected without amplification methods.

PMID- 15733594
TI  - Speech summer camp for treating articulation disorders in cleft palate patients.
AB  - INTRODUCTION: Compensatory articulation disorder (CAD) severely affects speech
      intelligibility of cleft palate children. CAD must be treated with speech
      therapy. Children can manage articulation better when they use language in event
      contexts such as every day routines. OBJECTIVE: The purpose of this paper is to
      study and compare two modalities of speech intervention in cleft palate children
      with associated CAD. The first modality is a conventional approach providing
      speech therapy in 1-h sessions, twice a week. The second modality is a speech
      summer camp in which children received therapy 4h per day, 5 days a week for a
      period of 3 weeks. We were aimed to determine if a speech summer camp could
      significantly enhance articulation in CP children with CAD. MATERIALS AND
      METHODS: Forty-five children with repaired cleft palates who exhibited CAD were
      studied. A matched control group of 45 children with repaired cleft palate who
      also exhibited CAD were identified. The patients included in the first group
      attended a speech summer camp for 3 weeks. The matched control subjects included
      in the second group received speech therapy aimed to correct CAD twice per-week
      in 1-h sessions. RESULTS: At the onset of either the summer camp or the speech
      therapy period, the severity of CAD was evenly distributed with non-significant
      differences across both groups of patients (p > 0.05). After the summer camp (3
      weeks) or 12 months of speech therapy sessions at a frequency of twice per-week,
      both groups of patients showed a significant decrease in the severity of their
      CAD (p < 0.05). However, when the distribution of the severity of CAD was
      compared at the end of the summer camp or the speech therapy period, non
      significant differences were found between both groups of patients (p > 0.05).
      CONCLUSIONS: A speech summer camp is a valid and efficient method for providing
      speech therapy in cleft palate children with compensatory articulation disorder.

PMID- 15733595
TI  - Comparison of performance by otolaryngologists, pediatricians, and general
      practioners on an otoendoscopic diagnostic video examination.
AB  - OBJECTIVE: To compare the performance of United States, South African, and Greek
      otolaryngologists, pediatricians, and general practitioners in recognizing the
      otoscopic examination findings of acute otitis media (AOM) and otitis media with
      effusion (OME) as presented in an otoendoscopic video evaluation test.
      DESIGN/SUBJECTS: Otolaryngologists, pediatricians, and general practitioners from
      the United States (n = 273, 2190, and 360 respectively), South Africa (n = 36,
      36, and 206), and Greece (n = 58, 115, and 126) viewed nine different video
      recorded otoscopic examinations, including pneumatic otoscopy of tympanic
      membranes. The ability to differentiate AOM, OME, and normal was ascertained.
      RESULTS: Overall, the average +/- standard deviation correct diagnosis on the
      otoscopic video exam by otolaryngologists was superior to pediatricians and
      general practitioners in all three countries: from the United States, it was 74
      +/- 16% for otolaryngologists versus 51 +/- 11% for pediatricians (p < 0.000l)
      and 46+/-21% for general practitioners (p < 0.0001); from South Africa, it was 72
      +/- 16% versus 53 +/- 21% (p = 0.16) and 47 +/- 19% (p = 0.002); and from Greece,
      it was 61 +/- 15% versus 36 +/- 12% (p < 0.003) and 39 +/- 10% (p = 0.009).
      CONCLUSIONS: A video-based otoscopy examination test may be a useful tool for
      evaluation of otoscopy-based diagnostic skills. Otolaryngologists performed
      significantly better than pediatricians in differentiating AOM, OME, and normal
      in such a test described here. However, all specialists who examine patients with
      AOM or OME may benefit from viewing video otoscopies to improve diagnostic
      accuracy.

PMID- 15733596
TI  - Evaluation of deaf children in a large series in Turkey.
AB  - OBJECTIVE: Evaluation of the deafness etiology, ear examination findings and
      hearing levels of deaf children in a large series. PATIENTS AND METHODS: We
      studied 840 deaf primary school children (486 male, 354 female, mean age 12.69+/
      3.52, range 5-22). A questionaire investigating the prenatal, perinatal and
      postnatal etiological causes was prepared and pedigree analysis was performed.
      After ENT examination, odyologic tests were performed. RESULTS: The etiological
      features of deafness were found for genetic causes as 429 cases (51.1%), 127
      children (15.1%) for acquired group and 284 children (33.8%) for unknown group.
      We confirmed 136 (15.5%) syndromic deaf children and 19 of them (13.9%) were
      autosomal recessive (AR), 105 of them (77.2%) were autosomal dominant (AD), six
      (4.4%) of them were X-linked. Two hundred and ninety-three deaf (33.4%) children
      were in the familial nonsyndromic group. In this group, the inheritance of 255
      (87%) were AR, 23 (7.8%) were AD and 15 (5.2%) were X-linked recessive. Febrile
      convulsion was identified as the most common etiology in 36 (4.3%) cases in the
      acquired group. Three hundred and twenty-two (67.7%) children had profound HL
      (above 91 dB), 111 (23.3%) had severe HL and 43 (9%) had moderately severe HL.
      Sensorineural HL was found in 439 (92.2%) and mixed type hearing loss was seen 37
      (7.8%) of 476 cases. We found many major and minor abnormalities and ocular, ear
      and dental pathologies. The prevalence of ear diseases was found in 203 (24.2%)
      of children. Impacted wax was found in 80 (9.5%) of 840 children with otoscopic
      examination and was the most common pathology, retraction in 70 (8.3%) and
      perforation in 15 (1.8%) followed it. CONCLUSION: Preventable ear disease are
      important health problems among school children for the deaf because these
      diseases can affect the real level and type of deafness, so determining early
      diagnostic criteria, ear diseases and minor abnormalities is important for early
      rehabilitation. Syndromes can be prevented in pregnancy, infections can be
      prevented in prenatal or postnatal period but unknown group cannot be prevented
      although the unknown etiology can be reduced by multidiciplinary approach.

PMID- 15733597
TI  - Relationship between pediatric sinusitis and middle turbinate pneumatization-
      ethmoidal sinus pyocele thought to be caused by middle turbinate pneumatization.
AB  - OBJECTIVE: To investigate whether the presence of pediatric middle turbinate
      pneumatization causes narrowing of the ostiomeatal complex (OMC) and is
      associated with the development of paranasal sinusitis. METHODS: CT scans of 190
      nasal sides of 95 children (1-15 years old) were analyzed for the presence of
      middle turbinate pneumatization and mucosal thickness in the paranasal sinus.
      RESULTS: Middle turbinate pneumatization was detected in nine (4.6%) of the nasal
      cavities. Only one of these sides was in a patient younger than 10 years of age,
      while the other eight sides were in patients at least 13 years old. In six of
      those nine sides with pneumatization, paranasal sinusitis was also found.
      However, the images showed that in five sides the middle turbinate pneumatization
      itself did not obstruct the OMC. In addition, the mean +/- standard deviation
      (S.D.) of the total score for the paranasal sinus opacification on the side which
      had the middle turbinate pneumatization was 5.67 +/- 2.95. The corresponding
      value for the 76 sides without pneumatization was 5.29 +/- 2.53, and the
      difference between these mean total scores was not statistically significant.
      However, in one side, the OMC was obstructed or narrowed due to the middle
      turbinate pneumatization, and an ethmoidal sinus pyocele formed on this side.
      CONCLUSION: A causal relationship was not found between middle turbinate
      pneumatization and the mechanism of development of paranasal sinusitis in
      children. However, in the event that the OMU becomes obstructed at some time,
      frequent cycles of improvement and aggravation of pediatric paranasal sinusitis
      may occur and lead to the development of a serious condition.

PMID- 15733598
TI  - The potential inflammatory role of arginase and iNOS in children with chronic
      adenotonsillar hypertrophy.
AB  - OBJECTIVE: Nitric oxide (NO) induced tissue damage has been implicated in the
      pathogenesis of several diseases. Although recurrent/chronic tonsillitis and
      hypertrophy are still the most frequent surgical procedures carried out on
      children in order to cure these pathologies, etiopathogenetic mechanisms
      underlying these entities are still unknown. We aimed to investigate the
      potential inflammatory role of NO regulatory enzymes, arginase and inducible
      nitric oxide synthase (iNOS), in children with adenotonsillar hypertrophy.
      MATERIALS AND METHODS: The study consisted of 22 children with chronic
      adenotonsillar hypertrophy and 30 control subjects with similar age and sex. All
      the patients and/or their parents had complaints of snoring, mouth breathing and
      pausing of breathe during sleep at least 6 months. All patients underwent an
      adenotonsillectomy operation under general anesthesia with curettage and cold
      dissection methods. Venous blood samples were taken pre-operatively and 4 weeks
      post-operatively. iNOS activity was based on the diazotization of sulfanilic acid
      by nitric oxide at acid pH and subsequent coupling to N-(1-naphthtyl)
      ethylenediamine. Arginase activity was measured by the spectrophotometric method.
      RESULTS: The mean pre-operative and post-operative arginase activities in patient
      group were 4283.7 +/- 1823.7 and 2754.5 +/- 889.3 IU/L, respectively. In the
      control group, mean arginase activity was 2254.7 +/- 903 IU/L. When pre-, post
      operative and control arginase values were compared with each other, the mean
      activity in pre-operative activity was significantly different from the post
      operative and control values (p < 0.001). In the patient group, the mean levels
      of pre- and post-operative iNOS were 2.84 +/- 1.16 and 1.99 +/- 0.78 IU/ml,
      respectively. The difference was statistically significant (p = 0.007).
      Similarly, post-operative and control values were not significantly different (p
      > 0.05). CONCLUSION: The results of the present study supports that L-arginine:NO
      pathway may be key the participant in the pathogenesis of chronic adenotonsillar
      disease; arginase and iNOS activities are altered in children with adenotonsillar
      hypertrophy and this alteration improves after tonsillectomy.

PMID- 15733599
TI  - Hearing function in Nigerian children with a family history of type 2 diabetes.
AB  - OBJECTIVE: Consequent on our previous observations [F.E. Ologe, E.O. Okoro, Type
      2 diabetes and hearing loss in black Africans, Diabetic Med. (in press).], we
      investigated whether abnormality in auditory function can precede overt diabetes
      in individuals with a genetic predisposition to type 2 diabetes. METHOD:
      Frequency specific pure tone audiograms (125, 250, 500, 1000, 2000, 3000, 4000,
      8000 Hz) and fasting blood glucose (FBG) and 2h post prandial blood glucose
      (2hrPBG) levels were measured in Nigerian children aged 9-19 years with at least
      a biologic parent with type 2 diabetes and compared with controls (contemporaries
      with non-diabetic parents). RESULTS: : Both groups were similar in gender mix,
      age, body sizes, FBS, 2PPhr BG, SBP; the values being (chi(2) = 0.04, d.f. = 1, p
      = 0.84); 14.32 +/- 2.29 years versus 14.77 +/- 3.10 years, 19.47 +/- 1.82 kg/m(2)
      versus 18.66 +/- 3.12 kg/m(2); 4.26 +/- 0.68 mmol versus 4.04 +/- 0.61 mmol; 5.07
      +/- 0.95 mmol versus 5.16 +/- 1.04 mmol; 103.73 +/- 9.62 mmHg versus 100.07 +/-
      13.77 mmHg for control and offspring of diabetic individuals, respectively.
      Similarly, pure-tone air-conduction audiograms were comparable (p > 0.5) in both
      groups. CONCLUSION: The data shows normal glucose metabolism in teenage offspring
      of type 2 diabetes and a pattern of audiogram not different from those observed
      in their counterparts without a genetic predisposition to type 2 diabetes.

PMID- 15733600
TI  - Failed newborn hearing screens as presentation for otitis media with effusion in
      the newborn population.
AB  - OBJECTIVES: Evaluate the prevalence of middle ear disease in infants failing a
      newborn hearing screening program. Review the outcomes of those infants diagnosed
      with or without middle ear disease after failed hearing screen. DESIGN:
      Retrospective chart review of 76 patients referred to a tertiary care institution
      for evaluation of a failed newborn hearing screening test. SETTING: Arkansas
      Children's Hospital, Little Rock, Arkansas. RESULTS: Seventy-six patients were
      referred for failed OAEs and complete otolaryngology evaluation. Mean age at the
      time of referral was 3 months (0.25 years) old. OME was identified in 64.5% of
      the patients. ABR confirmed a suspected hearing loss in 15 patients (78.9%)
      without middle ear disease. Effusion resolved without surgical intervention in
      65.3% of infants, while 17 (34.7%) of the infants required tubes. SNHL was
      subsequently identified in 11% of infants after resolution of the effusion.
      CONCLUSIONS: OME is a common cause of failed infant hearing screens, and should
      be looked for prior to definitive diagnostic hearing testing. OME resolves in the
      majority of infants, but tube insertion is necessary to allow for diagnostic
      testing in nearly one third of infants. The majority of infants without OME had
      SNHL confirmed. SNHL was also identified in 11% of infants with OME after
      resolution of the effusion.

PMID- 15733601
TI  - Electron microscopy findings in the nasal mucosa of a patient with stenosis of
      the nasal vestibule.
AB  - The nasal mucosa humidifies, warms and filters inspired air before it passes to
      the lower respiratory tract. In order to maintain the physiological activity of
      the respiratory epithelium, a certain amount of airflow is required. This report
      describes electron microscopy findings in the nasal mucosa of a patient who had
      decreased airflow through the nose due to stenosis of the nasal vestibule.
      Electron microscopic examination of the nasal mucosa revealed stratified squamous
      epithelium composed of markedly degenerated cells. The findings of abnormal
      mucosal structure highlight another negative consequence of nasal obstruction in
      addition to abnormal physiological function of the nose. The negative impact of
      diminished airflow on the nasal mucosa should be considered in any case where the
      patient has a condition that can lead to partial or total loss of airflow through
      the nose.

PMID- 15733602
TI  - Auricular seroma in a preterm infant as a severe complication of nasal continuous
      positive airway pressure (nCPAP).
AB  - Nasal continuous positive airway pressure (nCPAP) in preterm infants is closely
      linked to improvements in the primary management of respiratory failure. We
      report on a severe complication involving the external ear, which is usually
      covered by the fixing straps of the nCPAP application system. The very low
      birthweight infant (233/7 weeks' gestation) was treated with nCPAP for more than
      2 months. At the age of 51 days, the child developed a fluctuating seroma of the
      right external ear. Applied surgical treatments including punctation and
      compression of the ear resulted in full recovery after 3 months. Due to shearing
      forces associated with straps used for attaching the nasal application system,
      the infant developed a severe auricular trauma. Ear trauma can be minimised by
      careful padding of these straps. Continuous monitoring of the nCPAP-system,
      including the straps, is required.

PMID- 15733603
TI  - An isolated hyoid fracture secondary to sport injury. A case report and review of
      literature.
AB  - A 16-year-old boy sustained a fracture of the hyoid bone following closed neck
      injury from a hockey puck. Though commonly occurring in association of other
      fractures of the laryngeal skeleton, the fracture was isolated and a
      comprehensive evaluation implicated it solely for the clinical picture. Our
      review of the English literature displays the diversity of opinion on
      classification and treatment. It also indicates, however, that hyoid fractures
      are usually managed successfully with minimum intervention as indeed our case
      was.

PMID- 15733604
TI  - Atypical angiofibromas: a report of four cases.
AB  - In this study, our four patients with angiofibroma with various atypical features
      are presented. Related literature is reviewed and criteria for atypicality are
      proposed. 14 patients, diagnosed and treated for angiofibroma in the
      Otorhinolaryngology Department of Faculty of Medicine in Uludag University
      between January 1992 and December 2003, have been evaluated. The files of the
      patients were examined and four patients with atypical characteristics have been
      included in the study. Angiofibromas presenting with at least one of the
      following criteria such as origin or location other than nasopharynx, presenting
      complaints other than nasal obstruction or epistaxis, aged younger than seven or
      older than 25, female sex, atypical histopathology and multifocalitiy were
      considered as "atypical". Four of 14 angiofibromas (28.5%), which were diagnosed
      and treated in our clinic, had atypical features. The reasons for atypicality
      were unusual localization in three patients and uncommon initial symptom in one
      case. In the atypical localization group, neoplasm was located in tonsil in one
      case, and in inferior turbinate in two patients. The only patient with atypical
      initial symptom presented with a bulging in the cheek. The patients, who have
      different characteristics other than classical angiofibromas, may be called
      "Atypical Angiofibroma (AAF)", under the scope of the related literature and our
      experience. These patients should be included in atypical group according to the
      characteristics such as, localization, symptom, age, sex, histopathology and
      multifocality.

PMID- 15733605
TI  - A rare complication of embolization in juvenile nasopharyngeal angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma (JNA) is one of the most common benign nasal
      cavity tumors of adolescence. It exhibits a strong tendency to bleed and despite
      being microscopically benign, its behavior is locally aggressive. Preoperative
      embolization is helpful to minimize intraoperative bleeding. However,
      embolization procedure may have some important thromboembolic complications such
      as central retinal artery occlusion. In this article, a young male with juvenile
      nasopharyngeal angiofibroma, who lost his vision in the left eye following
      embolization was presented and the possible therapeutic options in such a
      complication were discussed.

PMID- 15733606
TI  - Congenital sialolipoma of the parotid gland first reported case and review of the
      literature.
AB  - Tumours of the parotid gland in children are uncommon, and represent only 1.3% of
      all benign salivary tumours. Lipomas of the parotid are also rare, and account
      for 0.5% of all parotid gland tumours. Sialolipoma is a new variant of salivary
      gland lipoma, consisting of adipose and glandular tissue that was first proposed
      by Nagao et al. in 2001. Ten cases of parotid gland lipoma associated with
      glandular elements have been previously reported in the literature. All have been
      in adults and none in children. We present the first reported case of congenital
      sialolipoma that had developed in a female infant. It was managed successfully by
      superficial parotidectomy undertaken at ten weeks of age.

PMID- 15733608
TI  - Obesity: overview of an epidemic.

PMID- 15733609
TI  - The regulation of energy balance by the central nervous system.

PMID- 15733610
TI  - Obesity, psychiatric status, and psychiatric medications.

PMID- 15733611
TI  - Obesity and eating disorders.

PMID- 15733612
TI  - Body image and obesity in adulthood.

PMID- 15733613
TI  - Medical evaluation of the obese individual.

PMID- 15733614
TI  - Behavioral assessment and treatment overview.

PMID- 15733615
TI  - Dietary approaches to the treatment of obesity.

PMID- 15733616
TI  - Physical activity recommendations in the treatment of obesity.

PMID- 15733617
TI  - Behavioral treatment of obesity.

PMID- 15733618
TI  - Commercial and self-help programs for weight control.

PMID- 15733619
TI  - Drug treatment of obesity.

PMID- 15733620
TI  - Surgical treatment of obesity.

PMID- 15733621
TI  - Public policy and obesity: the need to marry science with advocacy.

PMID- 15733622
TI  - Neuroleptic-induced movement disorders: an overview.

PMID- 15733623
TI  - Huntington's disease and related disorders.

PMID- 15733624
TI  - Insights into morphine-induced plasticity and spinal tolerance.

PMID- 15733625
TI  - Mechanisms of the placebo response and their impact on clinical trials and
      clinical practice.

PMID- 15733626
TI  - Altered primary afferent anatomy and reduced thermal sensitivity in mice lacking
      galectin-1.
AB  - The transmission of nociceptive information occurs along non-myelinated, or
      thinly myelinated, primary afferent axons. These axons are generally classified
      as peptidergic (CGRP-expressing) or non-peptidergic (IB4-binding), although there
      is a sub-population that is both CGRP-positive and IB4-binding. During neuronal
      development and following injury, trophic factors and their respective receptors
      regulate their survival and repair. Recent reports also show that the
      carbohydrate-binding protein galectin-1 (Gal1), which is expressed by nociceptive
      primary afferent neurons during development and into adulthood, is involved in
      axonal pathfinding and regeneration. Here we characterize anatomical differences
      in dorsal root ganglia (DRG) of Gal1 homozygous null mutant mice (Gal1(-/-)), as
      well as behavioural differences in tests of nociception. Gal1(-/-) mice have a
      significantly reduced proportion of IB4-binding DRG neurons, an increased
      proportion of NF200-immunoreactive DRG neurons, increased depth of central
      terminals of IB4-binding and CGRP-immunoreactive axons in the dorsal horn, and a
      reduced number of Fos-positive second order neurons following thermal (cold or
      hot) stimulation. While there is no difference in the total number of axons in
      the dorsal root of Gal1(-/-) mice, there are an increased number of myelinated
      axons, suggesting that in the absence of Gal1, neurons that are normally destined
      to become IB4-binding instead become NF200-expressing. In addition, mice lacking
      Gal1 have a decreased sensitivity to noxious thermal stimuli. We conclude that
      Gal1 is involved in nociceptive neuronal development and that the lack of this
      protein results in anatomical and functional deficits in adulthood.

PMID- 15733627
TI  - Nitrous oxide analgesia in humans: acute and chronic tolerance.
AB  - Electrical tooth stimulation was used to investigate whether humans develop
      tolerance to nitrous oxide (N(2)O) analgesia within a single administration as
      well as over repeated administrations. In a double-blind cross-over experiment,
      77 subjects received a 40-min administration of 38% N(2)O at one session and
      placebo gas at the other. The sessions were separated by 1 week and the order of
      gas administration was counterbalanced. Acute analgesic tolerance developed for
      pain threshold but not for detection threshold. There was no evidence of a
      hyperalgesic rebound effect following cessation of the N(2)O administration. In a
      second double-blind experiment, 64 subjects received both 30-min of placebo gas
      and 30-min of 35% N(2)O, separated by a 35-min gas wash-out period, during each
      of five sessions. Sensory thresholds were assessed prior to drug or placebo
      administration (baseline) and between 7-12 and 25-30 min of gas administration. A
      control group of 16 subjects received only placebo gas at these five sessions.
      During a sixth session, the experimental procedures were similar to the previous
      sessions except that the control group received N(2)O for the first time and the
      experimental group was sub-divided to test for conditioned drug effects. For both
      detection and pain threshold measures, acute tolerance developed during the
      initial N(2)O exposure and chronic tolerance developed over repeated
      administrations. Although chronic tolerance developed, a test for Pavlovian drug
      conditioning found no evidence of conditioned effects on sensory thresholds. In
      conclusion, acute and chronic tolerance develop to N(2)O's analgesic effects in
      humans.

PMID- 15733628
TI  - Comparison of pain syndromes associated with nervous or somatic lesions and
      development of a new neuropathic pain diagnostic questionnaire (DN4).
AB  - Few studies have directly compared the clinical features of neuropathic and non
      neuropathic pains. For this purpose, the French Neuropathic Pain Group developed
      a clinician-administered questionnaire named DN4 consisting of both sensory
      descriptors and signs related to bedside sensory examination. This questionnaire
      was used in a prospective study of 160 patients presenting with pain associated
      with a definite neurological or somatic lesion. The most common aetiologies of
      nervous lesions (n=89) were traumatic nerve injury, post herpetic neuralgia and
      post stroke pain. Non-neurological lesions (n=71) were represented by
      osteoarthritis, inflammatory arthropathies and mechanical low back pain. Each
      patient was seen independently by two experts in order to confirm the diagnosis
      of neuropathic or non-neuropathic pain. The prevalence of pain descriptors and
      sensory dysfunctions were systematically compared in the two groups of patients.
      The analysis of the psychometric properties of the DN4 questionnaire included:
      face validity, inter-rater reliability, factor analysis and logistic regression
      to identify the discriminant properties of items or combinations of items for the
      diagnosis of neuropathic pain. We found that a relatively small number of items
      are sufficient to discriminate neuropathic pain. The 10-item questionnaire
      developed in the present study constitutes a new diagnostic instrument, which
      might be helpful both in clinical research and daily practice.

PMID- 15733629
TI  - Do men and women differ in their response to interdisciplinary chronic pain
      management?
AB  - Women report more pain than men. It also seems that gender may moderate responses
      to pharmacological agents used to combat pain, suggesting that men and women
      differ in treatment efficacy. Recent research suggests that gender differences
      may also exist in response to interdisciplinary pain management interventions.
      We, therefore, report data from a treatment-outcome program at a UK Pain
      Management Unit. The sample consisted of 98 chronic pain patients (33 males; 65
      females) who completed a series of measures relating to pain and distress at
      three different time points: immediately prior, on completion, and 3 months
      following an interdisciplinary pain management intervention. The pain management
      intervention consisted of a 3- or 4-week residential program that aimed to
      enhance daily functioning, and which involved physiotherapists, occupational
      therapists, a nurse, physicians, and clinical psychologists. Analyses revealed
      that the pain management intervention produced improvements in a range of domains
      of outcome for both men and women, and that such effects were sustained at 3
      months following treatment. However, although both men and women exhibited
      significant post-treatment reduction in measures of current pain intensity and
      with one measure of pain-related distress, at 3 months following treatment men
      showed similar reductions as at post-treatment, whereas for women there were no
      significant differences from pre-treatment scores. This suggests that gender may
      play a role in reports of pain and distress following interdisciplinary chronic
      pain management. However, the current results are different from those previously
      reported. We discuss potential reasons for such differences.

PMID- 15733630
TI  - Psychosocial work characteristics in relation to neck and upper limb symptoms.
AB  - The aim of this study was to investigate the relationship between psychosocial
      work characteristics and neck and upper limb symptoms and to examine to what
      extent this relationship could be explained by other risk factors. Data were used
      from a prospective cohort study in a working population, with a follow-up period
      of 3 years. The 3-year cumulative incidence rates of neck or upper limb symptoms,
      neck/shoulder symptoms and elbow/wrist/hand symptoms were 32, 24 and 15%,
      respectively. After adjustment for potential confounders high job demands was
      identified as a risk factor for neck/shoulder symptoms (RR: 2.1; CI: 1.2-3.6) and
      elbow/wrist/hand symptoms (RR: 1.9; CI: 1.0-3.7), and low social support of co
      workers was identified as a risk factor for elbow/wrist/hand symptoms (RR: 2.2;
      CI: 1.0-4.9). Partly, but not exclusively, these relationships were intermediated
      by an increased exposure to physical risk factors and increased stress symptoms.
      Personal characteristics did not considerably influence the main effects of the
      identified risk factors.

PMID- 15733631
TI  - Is successful rehabilitation of complex regional pain syndrome due to sustained
      attention to the affected limb? A randomised clinical trial.
AB  - In complex regional pain syndrome (CRPS1) initiated by wrist fracture, a motor
      imagery program (MIP), consisting of hand laterality recognition followed by
      imagined movements and then mirror movements, reduces pain and disability, but
      the mechanism of effect is unclear. Possibilities include sustained attention to
      the affected limb, in which case the order of MIP components would not alter the
      effect, and sequential activation of cortical motor networks, in which case it
      would. Twenty subjects with chronic CRPS1 initiated by wrist fracture and who
      satisfied stringent inclusion criteria, were randomly allocated to one of three
      groups: hand laterality recognition, imagined movements, mirror movements
      (RecImMir, MIP); imagined movements, recognition, imagined movements (ImRecIm);
      recognition, mirror movements, recognition (RecMirRec). At 6 and 18 weeks,
      reduced pain and disability were greater for the RecImMir group than for the
      other groups (P<0.05). Hand laterality recognition imparted a consistent
      reduction in pain and disability across groups, however, this effect was limited
      in magnitude. Imagined movements imparted a further reduction in pain and
      disability, but only if they followed hand laterality recognition. Mirror
      movements also imparted a reduction in pain and disability, but only when they
      followed imagined movements. The effect of the MIP seems to be dependent on the
      order of components, which suggests that it is not due to sustained attention to
      the affected limb, but is consistent with sequential activation of cortical motor
      networks.

PMID- 15733632
TI  - Characterization of morphine-induced hyperalgesia in male and female rats.
AB  - The pain enhancing (hyperalgesic) effect of morphine was characterized in
      relation to pain stimulus (thermal, mechanical), dose, mode of administration
      (acute, chronic), sex and mechanism. We found that a low (subanalgesic) dose of
      morphine enhanced the sensitivity to thermal and mechanical noxious stimuli in a
      dose- and sex-related manner. Morphine hyperalgesia was inversely related to dose
      (0.002-0.2mg/kg) and was more pronounced in female than male rats. The N-methyl-d
      aspartate receptor antagonist, ketamine, antagonized morphine hyperalgesia.
      Tolerance developed to hyperalgesia following repeated (chronic) dosing with low
      dose morphine. Several additional findings were noted in rats tolerant to
      morphine-induced hyperalgesia. The efficacy of an analgesic dose of morphine was
      increased (female rats). Sex-related differences in morphine's analgesic action
      (male>female) were attenuated. Development of tolerance to the analgesic effect
      of morphine was delayed. The present findings may have an implication for the use
      of mu opioids in the clinical setting.

PMID- 15733633
TI  - The organizational and activational effects of sex hormones on tactile and
      thermal hypersensitivity following lumbar nerve root injury in male and female
      rats.
AB  - Considerable evidence exists for sex differences in human pain sensitivity. Women
      typically report a higher incidence of various painful conditions and report that
      the conditions are more painful when compared to men. In the present study, we
      sought to determine whether sex differences in pain sensitivity are observed
      using a lumbar radiculopathy model of low back pain in the rat and whether
      removal or alteration of gonadal hormones at specific timepoints can modulate
      these sex differences. Pubertal and adult male and female Sprague-Dawley rats
      were castrated 2 or 6 weeks prior to L5 nerve root injury to determine the
      activational hormonal effects. In a separate study, neonatal male and female
      Sprague-Dawley rats were either castrated or injected with testosterone,
      respectively, on postnatal day one to determine the organizational effects of
      gonadal hormones on L5 nerve root injury-induced behavioral hypersensitivity. Our
      results demonstrate that there was a statistically significant sex difference in
      the magnitude of mechanical allodynia and thermal hyperalgesia following
      experimentally induced radiculopathy in the rat: females demonstrated decreased
      thresholds to tactile and thermal stimuli as compared to males. Furthermore, the
      enhanced female hypersensitivity was reversed in pubertal and adult animals
      ovariectomized 6 weeks, but not 2 weeks prior to L5 nerve root injury. Our
      results demonstrate that the activational effects of gonadal hormones mediate the
      enhanced female tactile and thermal hypersensitivity following L5 nerve root
      injury. These results suggest that manipulation of gonadal hormones may be a
      potential source for novel therapies for chronic pain in women.

PMID- 15733634
TI  - Evidence for a long-term influence on morphine tolerance after previous morphine
      exposure: role of neuronal glucocorticoid receptors.
AB  - Opioid analgesic tolerance is a pharmacological phenomenon that overtime
      diminishes the opioid analgesic effect. However, it remains unknown as to whether
      a previous opioid exposure would have a long-term influence on opioid tolerance
      upon subsequent opioid administration. Here, we show that the onset and degree of
      antinociceptive tolerance to a subsequent cycle of morphine exposure were
      substantially exacerbated in rats made tolerant to and then recovered from
      previous morphine administration, indicating a long-term influence from a
      previous morphine exposure on the development of morphine tolerance.
      Mechanistically, morphine exposure induced a cyclic AMP and protein kinase A
      dependent upregulation of neuronal glucocorticoid receptors (GR) within the
      spinal cord dorsal horn, which was maintained after discontinuation of morphine
      administration and significantly enhanced upon a second cycle of morphine
      exposure. Prevention of the GR upregulation with GR antisense oligonucleotides as
      well as inhibition of GR activation with the GR antagonist RU38486 effectively
      prevented the exacerbated morphine tolerance after subsequent cycles of morphine
      exposure. The results indicate that a previous morphine exposure could induce
      lasting cellular changes mediated through neuronal GR and influence morphine
      analgesia upon a subsequent exposure. These findings may have significant
      implications in clinical opioid therapy and substance abuse.

PMID- 15733635
TI  - Brain processing during mechanical hyperalgesia in complex regional pain
      syndrome: a functional MRI study.
AB  - Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory,
      motor and autonomic dysfunctions of still unknown origin. Pain and mechanical
      hyperalgesia are hallmarks of CRPS. There are several lines of evidence that
      central nervous system (CNS) changes are crucial for the development and
      maintenance of mechanical hyperalgesia. However, little is known about the
      cortical structures associated with the processing of hyperalgesia in pain
      patients. This study describes the use of functional magnetic resonance imaging
      (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS.
      Twelve patients, in whom previous quantitative sensory testing revealed the
      presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick
      hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by
      von-Frey filaments at the affected limb. For control, the identical stimulation
      was performed on the unaffected limb. fMRI was used to explore the corresponding
      cortical activations. Mechanical stimulation at the unaffected limb was non
      painful and mainly led to an activation of the contralateral primary
      somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices
      (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia)
      and led to a significantly increased activation of the S1 cortex (contralateral),
      S2 (bilateral), insula (bilateral), associative-somatosensory cortices
      (contralateral), frontal cortices and parts of the anterior cingulate cortex. The
      results of our study indicate a complex cortical network activated during pin
      prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not
      only involved in nociceptive, but also in cognitive and motor processing.

PMID- 15733636
TI  - Predicting the failure of disc surgery by a hypofunctional HPA axis: evidence
      from a prospective study on patients undergoing disc surgery.
AB  - Patients with postoperative ongoing sciatic pain have been shown to exhibit
      reduced cortisol levels along with enhanced IL-6 levels. The aim of the present
      study was to clarify the relationship between a reduced cortisol secretion and
      enhanced cytokine levels by performing a prospective study on patients with disc
      herniation. Twenty-two patients were examined before and after their disc
      surgery. Twelve healthy, pain-free subjects matched for age, education and gender
      constituted the control group. The preoperative examinations included the
      assessment of the diurnal pattern of cortisol secretion and the feedback
      sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis. Patients'
      subjective stress levels also were assessed during the preoperative examination.
      The diurnal pattern of cortisol secretion was again assessed during the
      postoperative examination. Furthermore, blood samples were collected to measure
      catecholamine, adrenocorticotropic hormone (ACTH)- and interleukin-6 (IL-6)
      levels before and after measuring the pressure pain thresholds (PPTs). An
      assessment of the sensitivity of circulating monocytes to the immunosuppressive
      effects of glucocorticoids was further included in the postoperative
      examinations. Failed back syndrome (FBS) patients (n=12) showed a reduced
      cortisol secretion in the morning hours and enhanced feedback sensitivity of the
      HPA axis. Furthermore, FBS patients displayed an increased in-vitro production of
      proinflammatory cytokines and a relative glucocorticoid resistance of pro
      inflammatory cytokine producing monocytes as compared to non-FBS patients (n=10)
      and controls. After PPT measurement FBS patients exhibited an increased
      norepinephrine but decreased epinephrine response, together with lower ACTH
      levels and a four times higher plasma IL-6 response. These findings suggest that
      chronically stressed patients are at a higher risk for a poor surgical outcome as
      their reduced cortisol secretion promotes the postoperative ongoing synthesis of
      proinflammatory cytokines.

PMID- 15733637
TI  - Sensory and motor effects of experimental muscle pain in patients with lateral
      epicondylalgia and controls with delayed onset muscle soreness.
AB  - This study compares the effect of experimental muscle pain on deep tissue
      sensitivity and force attenuation in the wrist extensors of patients with lateral
      epicondylalgia (n=20), and healthy controls (n=20) with experimentally induced
      sensori-motor characteristics simulating lateral epicondylalgia. Delayed onset
      muscle soreness (DOMS) in wrist extensors of healthy controls was induced by
      eccentric exercise in one arm 24h prior to injection (Day 0). Saline-induced pain
      intensity (visual analogue scale, VAS), distribution, and quality were assessed
      quantitatively in both arms for both groups. Pressure pain thresholds (PPT) were
      assessed at three different sites in the wrist extensors. Maximal grip force and
      wrist extension force were recorded. In response to saline-induced pain in the
      extensor carpi radialis brevis, regardless of arm, the patient group demonstrated
      a significantly quicker pain onset (P<0.01), mapped larger pain areas and more
      referred pain areas, compared to healthy controls (P<0.03). Pain persisted
      significantly longer in the sore arm of the patient group, compared with all
      other arms (P<0.02). Patients demonstrated significant bilateral hyperalgesia at
      extensor carpi radialis brevis during and post saline-induced pain compared to
      pre-injection and healthy controls (P<0.04). The sore arm in patients and the
      DOMS arms in healthy subjects showed significantly reduced maximal force
      (P<0.0001), at all Day 1 times compared with the control arms. In patients, the
      bilateral increase in deep tissue sensitivity and enlarged referred pain areas
      during saline-induced pain might suggest involvement of central sensitisation.

PMID- 15733638
TI  - Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast
      cells in the thalamus of female but not male mice.
AB  - Mast cells are restricted to the leptomeninges and thalamus of healthy mice.
      These populations are increased by stress and highly sensitive to reproductive
      hormones. To examine the influence of nociception, a form of stress, on thalamic
      mast cells, we ligated the left fifth lumbar spinal nerve of male and female mice
      to induce hyperalgesia. Two, 7 and 14 days later, mice were killed and thalami
      examined histologically using toluidine blue stain. The total number of thalamic
      mast cells was not influenced by ligation of the spinal nerve compared to sham
      operation in either female or male mice. However, in females, the percent of
      thalamic mast cells located on the side of the thalamus contralateral to the
      ligation was greater on days 2 and 7, coincident with mechanical hyperalgesia. At
      these times, areas in which mast cells were most dense contralateral to nerve
      injury included the posterior (Po) and lateral geniculate (LG) nuclei compared to
      their symmetrical distribution in sham-operated mice. These data suggest that
      local nociceptive signals to each side of the thalamus rather than stress
      hormones influence the location of mast cells during the development of allodynia
      and hyperalgesia. In addition, both hyperalgesia and mast cell distribution
      induced by nerve-ligation differ in females compared to males, reflecting a novel
      neuroimmune response to pain within the CNS.

PMID- 15733639
TI  - Physical and psychological factors predict outcome following whiplash injury.
AB  - Predictors of outcome following whiplash injury are limited to socio-demographic
      and symptomatic factors, which are not readily amenable to secondary and tertiary
      intervention. This prospective study investigated the predictive capacity of
      early measures of physical and psychological impairment on pain and disability 6
      months following whiplash injury. Motor function (ROM; kinaesthetic sense;
      activity of the superficial neck flexors (EMG) during cranio-cervical flexion),
      quantitative sensory testing (pressure, thermal pain thresholds, brachial plexus
      provocation test), sympathetic vasoconstrictor responses and psychological
      distress (GHQ-28, TSK, IES) were measured in 76 acute whiplash participants. The
      outcome measure was Neck Disability Index scores at 6 months. Stepwise regression
      analysis was used to predict the final NDI score. Logistic regression analyses
      predicted membership to one of the three groups based on final NDI scores (<8
      recovered, 10-28 mild pain and disability, >30 moderate/severe pain and
      disability). Higher initial NDI score (1.007-1.12), older age (1.03-1.23), cold
      hyperalgesia (1.05-1.58), and acute post-traumatic stress (1.03-1.2) predicted
      membership to the moderate/severe group. Additional variables associated with
      higher NDI scores at 6 months on stepwise regression analysis were: ROM loss and
      diminished sympathetic reactivity. Higher initial NDI score (1.03-1.28), greater
      psychological distress (GHQ-28) (1.04-1.28) and decreased ROM (1.03-1.25)
      predicted subjects with persistent milder symptoms from those who fully
      recovered. These results demonstrate that both physical and psychological factors
      play a role in recovery or non-recovery from whiplash injury. This may assist in
      the development of more relevant treatment methods for acute whiplash.

PMID- 15733640
TI  - ERK is sequentially activated in neurons, microglia, and astrocytes by spinal
      nerve ligation and contributes to mechanical allodynia in this neuropathic pain
      model.
AB  - Activation of extracellular signal-regulated kinase (ERK), a mitogen activated
      protein kinase (MAPK), in dorsal horn neurons contributes to inflammatory pain by
      transcription-dependent and -independent means. We have now investigated if ERK
      is activated in the spinal cord after a spinal nerve ligation (SNL) and if this
      contributes to the neuropathic pain-like behavior generated in this model. An L5
      SNL induces an immediate (<10 min) but transient (<6 h) induction of phosphoERK
      (pERK) restricted to neurons in the superficial dorsal horn. This is followed by
      a widespread induction of pERK in spinal microglia that peaks between 1 and 3
      days post-surgery. On Day 10, pERK is expressed both in astrocytes and microglia,
      but by Day 21 predominantly in astrocytes in the dorsal horn. In the L5 DRG SNL
      transiently induces pERK in neurons at 10 min, and in satellite cells on Day 10
      and 21. Intrathecal injection of the MEK (ERK kinase) inhibitor PD98059 on Day 2,
      10 or 21 reduces SNL-induced mechanical allodynia. Our results suggest that ERK
      activation in the dorsal horn, as well as in the DRG, mediates pain through
      different mechanisms operating in different cells at different times. The
      sequential activation of ERK in dorsal horn microglia and then in astrocytes
      might reflect distinct roles for these two subtypes of glia in the temporal
      evolution of neuropathic pain.

PMID- 15733641
TI  - Investigation of the paradoxical painful sensation ('illusion of pain') produced
      by a thermal grill.
AB  - A paradoxical painful sensation can be elicited by the simultaneous application
      of innocuous warm and cold stimuli to the skin. In the present study, we analyzed
      the conditions of production of this unique experimental illusion of pain in 52
      healthy volunteers (27 men, 25 women). The stimuli were produced by a thermode
      composed of six bars whose temperature was controlled by Peltier elements. The
      temperature of alternate (even- and odd-numbered) bars could be controlled
      independently to produce various patterns of the 'thermal grill'. After measuring
      the cold and heat pain thresholds, a series of combinations of warm and cold
      stimuli, whose distance to the thermal pain threshold was at least 4 degrees C,
      were applied on the palmar surface of the right hand during 30s. After each
      stimulus, the subjects had to describe and rate their sensations on visual analog
      scales. Paradoxical painful sensations, mostly described as burning, were
      reported by all the subjects but three. However, the phenomenon was less frequent
      in approximately one third of ('low responder') volunteers. The frequency and
      intensity of such painful sensations were directly related to the magnitude (i.e.
      5-25 degrees C) of the difference of the temperature between the warm and cold
      bars of the grill. The combination of increasingly colder temperature to a given
      warm temperature induces similar effects as combining increasingly warmer
      temperature to a given cold temperature. These results suggest that pain can be
      the result of a simple addition of non-noxious warm and cold signals.

PMID- 15733642
TI  - Excitatory and modulatory effects of inflammatory cytokines and neurotrophins on
      mechanosensitive group IV muscle afferents in the rat.
AB  - In inflamed tissue--including skeletal muscle--the concentrations of cytokines
      and neurotrophins are known to increase. However, nothing is known about a
      possible contribution of these agents to muscle pain and hyperalgesia. The
      present study investigated acute effects of cytokines and neurotrophins on
      response properties of slowly conducting muscle afferents. In anaesthetised rats,
      the impulse activity of single mechanosensitive group IV fibres innervating the
      gastrocnemius-soleus muscle was recorded and tumour necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6), nerve growth factor (NGF), or brain-derived
      neurotrophic factor (BDNF) were injected into the muscle. Changes in the
      mechanosensibility of the endings following administration of the agents were
      tested with repeated pressure stimuli of defined forces. A low mechanical
      threshold in the innocuous range was found in 44.4% of the units tested, 55.6%
      required strong, potentially tissue-damaging pressure stimuli for activation. NGF
      excited only units that had a high mechanical threshold, while IL-6 was a
      stimulant for low-threshold mechanosensitive units only. TNF-alpha and BDNF did
      not excite group IV units but had a desensitising action: after TNF-alpha or
      BDNF, the response magnitudes to pressure stimuli decreased significantly. The
      data indicate that cytokines and neurotrophins influence the impulse activity and
      mechanosensitivity of group IV muscle afferent units. These effects could be of
      functional significance when the agents are released from muscle cells under
      pathophysiological circumstances.

PMID- 15733643
TI  - Residual complaints following lumbar disc surgery: prognostic indicators of
      outcome.
AB  - Physical as well as psychological features might be important prognostic factors
      for residual complaints following lumbar disc surgery in primary care. No studies
      have yet investigated both factors simultaneously. The aim of this prospective
      cohort study was to identify indicators of the short and long-term outcome of
      residual complaints following lumbar disc surgery. Patients (n=105), aged between
      18 and 65 years, were included if they still suffered residual complaints 6 weeks
      after first-time lumbar disc surgery and had therefore been referred to
      physiotherapy. All potential indicators were measured at baseline except
      treatment expectancy, which was measured after two treatment sessions enabling
      patients to rate treatment expectancy based on their actual perception of the
      treatment. Dimensions of recovery included perceived recovery, functional status,
      and pain intensity (back and leg) at the 3-month and 12-month follow-up. It was
      found that high treatment expectancy was associated with a favorable outcome on
      perceived recovery and functional status, both at the 3 and the 12-month follow
      up. Taking pain medication and a poor functional status at baseline were
      associated with poor perceived recovery and functional status at both follow-up
      measurements. Leg pain and back pain at baseline were associated with residual
      leg and back pain at the 3 and the 12-month follow-up, respectively. The results
      for perceived recovery and functional status were rather robust. However, for leg
      pain and back pain, the results were less stable. Apparently, the clinical course
      to recovery of residual leg pain and residual back pain is not strongly
      influenced by these indicators.

PMID- 15733644
TI  - Genetic variations in IL6 associate with intervertebral disc disease
      characterized by sciatica.
AB  - Intervertebral disc disease (IDD) characterized by sciatica is a common disorder
      affecting about 5% of individuals. Environmental factors can predispose to this
      disease, but IDD has a strong genetic background. Recent evidence suggests that
      inflammation is one of the key factors in the etiology of IDD. Here, a possible
      role of the inflammatory mediator genes was studied in 155 patients with IDD
      related sciatica and 179 controls. Forty-eight patients were analyzed for
      mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10
      candidate cytokine genes (IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10,
      IFNG) were genotyped from all subjects. No disease-causing mutations were
      identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however,
      significantly different between the two groups for IL6 SNP, T15A in exon 5
      (P=0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more
      common in the patients (P=0.011; OR=4.4, 95% CI=1.2-15.7; AR=7.5%, 1.6-13.1%).
      Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C, G-174C, and
      T15A in exon 5. Haplotype GGGA was more common in the patients (P=0.011; OR=4.8,
      95% CI=1.6-14.5). To evaluate attributable risk, haplotype pairs were assigned
      for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR
      of 5.4 (95% CI=1.5-19.2). Association of GGGA with disease was highly significant
      (P=0.0033), and the associated AR was 6.8% (1.9-11.5%). These findings support
      the role of IL-6 genetic variations in discogenic pain.

PMID- 15733645
TI  - Role of central and peripheral mGluR5 receptors in post-operative pain in rats.
AB  - Metabotropic glutamate receptors (mGluRs) have previously been shown to play a
      role in pain transmission during inflammatory or neuropathic pain states.
      However, the role of mGluR5 in post-operative pain remains to be fully
      investigated. The present study was conducted to characterize analgesic activity
      of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) in the skin-incision-induced post
      operative pain model in rats. MPEP is a potent and selective mGluR5 antagonist
      with high affinity (K(i)=6.3+/-0.9 nM) in rat cortex using [(3)H]-MPEP as a
      radioligand, while not competing with the mGluR1-selective radioligand [(3)H]
      R214127 (K(i)>10,000 nM) in rat cerebellum. Post-operative pain was examined 2 h
      following surgery using weight-bearing (WB) difference between injured and
      uninjured paws as a measure of non-evoked pain. In this model, MPEP, as morphine,
      showed dose-dependent effects and full efficacy after systemic administration
      (ED(50)=15 mg/kg, i.p. for MPEP, ED(50)=1.3 mg/kg, s.c. for morphine). In
      addition, intrathecal (i.t.) and intracerebroventricular (i.c.v.) MPEP reduced WB
      difference (ED(50)=65 microg/rat i.t. and ED(50)=200 microg/rat i.c.v.).
      Interestingly, intraplantar (i.pl.) injection of MPEP either before or after
      surgery induced a similar reduction in WB difference (ED(50)=90 microg/rat,
      i.pl.) while contralateral i.pl. MPEP injection did not produce any effect. These
      results demonstrate that both peripheral and central mGluR5 receptors play a role
      in nociceptive transmission observed during post-operative pain. In addition, the
      data suggest that mGluR5 antagonists could offer a new therapeutic approach to
      the treatment of post-operative pain.

PMID- 15733646
TI  - Differential modulation of TMJ neurons in superficial laminae of trigeminal
      subnucleus caudalis/upper cervical cord junction region of male and cycling
      female rats by morphine.
AB  - Sex differences in the cellular responses to morphine were examined in an animal
      model of temporomandibular joint (TMJ) pain. TMJ-responsive neurons were recorded
      in the superficial laminae at the trigeminal subnucleus caudalis/upper cervical
      cord (Vc/C(2)) junction region, the initial site of synaptic integration for TMJ
      afferents, in male and cycling female rats under barbiturate anesthesia. Unit
      activity was evoked by local injection of bradykinin into the TMJ capsule at 30
      min intervals and the effects of morphine sulfate (0.03-3 mg/kg, i.v.) were
      assessed by a cumulative dose regimen. Morphine caused a dose-related inhibition
      of bradykinin-evoked unit activity in males and diestrous females in a naloxone
      reversible manner, while evoked unit activity in proestrous females was not
      reduced. The apparent sex hormone-related aspect of morphine analgesia was
      selective for evoked unit activity, since the spontaneous activity of TMJ units
      was reduced similarly in all groups, while the convergent cutaneous receptive
      field area of TMJ units did not change in any group. These results were
      consistent with the hypothesis that sex hormone status interacts with pain
      control systems to modify neural activity at the level of the Vc/C(2) junction
      region relevant for TMD pain.

PMID- 15733647
TI  - Inhibitors of serine/threonine protein phosphatases antagonize the
      antinociception induced by agonists of alpha 2 adrenoceptors and GABAB but not
      kappa-opioid receptors in the tail flick test in mice.
AB  - We previously reported that serine/threonine protein phosphatases (PPs) play a
      role in the antinociception induced by the mu-opioid receptor agonist morphine.
      In this study we evaluated the possible involvement of PPs on the antinociception
      induced by agonists of others G protein-coupled receptors in the tail flick test
      in mice. The subcutaneous administration of clonidine (0.25-4 mg/kg), baclofen (2
      32 mg/kg) or U50,488H (2-16 mg/kg) (agonists of alpha(2) adrenoceptors, GABA(B)
      and kappa-opioid receptors, respectively) produced dose-dependent
      antinociception. The antinociceptive effects of clonidine and baclofen were
      antagonized in a dose-dependent way by the protein phosphatase inhibitors okadaic
      acid (0.001-10 pg/mouse, i.c.v.) and cantharidin (0.001-10 ng/mouse, i.c.v.), and
      okadaic acid was 1000 times more potent than cantharidin in producing this
      effect. The effects of these drugs appear to be specifically due to the blockade
      of PPs, since L-norokadaone (an analogue of okadaic acid that has no effect on
      PPs) did not modify clonidine- or baclofen-induced antinociception over the wide
      range of doses used (0.001-1000 pg/mouse, i.c.v.). On the other hand, the
      antinociception induced by activation of kappa-opioid receptors with U50,488H was
      not modified by okadaic acid or cantharidin. In conclusion, our data support the
      idea that serine/threonine PPs are differentially involved in the antinociceptive
      effects of several agonists of G protein-coupled receptors in mice.

PMID- 15733648
TI  - Change of dorsal horn neurochemistry in a mouse model of neuropathic cancer pain.
AB  - We investigated some neurochemical changes that take place in the spinal cord
      dorsal horn in a mouse model of neuropathic cancer pain. The model was produced
      by inoculation of Meth-A sarcoma cells to the vicinity of the sciatic nerve,
      which resulted in growth of a tumor mass embedding the nerve. Hind paw-lifting, a
      behavioral sign of spontaneous pain, was at maximum on Day 18, but decreased
      thereafter. The decrease was likely caused by progression of motor paralysis. On
      Day 18, thermal and mechanical pain thresholds of the affected paw were
      significantly increased. Histologically, the sciatic nerve presented damages to
      both unmyelinated and myelinated fibers on Day 18, which were more pronounced on
      Day 25. In the spinal cord, c-Fos-positive cells were significantly increased in
      the superficial and deep layers on Day 18. The number of c-Fos-positive cells in
      the superficial layer correlated with the duration of paw-lifting. The increase
      in c-Fos-positive cells was still present on Day 25 despite decreased paw
      lifting. Substance P and calcitonin gene-related peptide were up-regulated on Day
      18 but down-regulated on Day 25. A marked up-regulation of dynorphin A (DynA) was
      present on Day 18 and persisted through Day 25. Our model caused progressive
      damage to the sciatic nerve and presented spontaneous pain-behavior while the paw
      became hyposensitive to mechanical and thermal stimuli. Since the up-regulation
      of DynA in the dorsal horn persisted and paralleled the increase in c-Fos
      positive cells, the release of DynA may be associated with spontaneous pain in
      our model.

PMID- 15733649
TI  - Peripheral and central antinociceptive action of Na+-K+-2Cl- cotransporter
      blockers on formalin-induced nociception in rats.
AB  - The possible local peripheral and spinal (intrathecal) antinociceptive effect of
      Na(+)-K(+)-2Cl(-) cotransporter (NKCC) inhibitors was investigated in the rat
      formalin test. Nociceptive flinching behavior induced by formalin (1%) injection
      in the hind paw was assessed following administration of cotransporter
      inhibitors. Local peripheral pretreatment in the ipsilateral paw with bumetanide
      (ED(30), 27.1+/-12.7 microg/paw), piretanide (ED(30), 109.2+/-21.6 microg/paw) or
      furosemide (ED(30), 34.3+/-5.0 microg/paw), but not vehicle (DMSO 100%), produced
      dose-dependent antinociception in phase 2 of the test. Local bumetanide had the
      greatest effect (approximately 70% antinociception). Bumetanide also inhibited
      formalin-induced flinching behavior during phase 1 (ED(30), 105.6+/-99.1
      microg/paw). Spinal intrathecal pretreatment with bumetanide (ED(30), 194.6+/
      97.9 microg), piretanide (ED(30), 254.4+/-104.9 microg) or furosemide (ED(30),
      32.0+/-6.9 microg), but not vehicle (DMSO 100%), also produced antinociception in
      phase 2. In this case, only intrathecal furosemide reduced flinching behavior
      during phase 1 (ED(30), 99.4+/-51.4 microg) and had the maximal antinociceptive
      effect in phase 2 (approximately 65% antinociception). The opioid receptor
      antagonist naloxone (2 mg/kg, s.c.) did not reverse antinociception induced by
      either peripheral or spinal administration of NKCC blockers. Our data suggest
      that the Na(+)-K(+)-2Cl(-) cotransporter localized in sensory neurons at
      intraspinal and peripheral sites is involved in formalin-induced nociception.

PMID- 15733650
TI  - Relationship between pain symptoms and referred sensory and trophic changes in
      patients with gallbladder pathology.
AB  - The relationship was investigated between algogenic potential of gallbladder
      pathology and occurrence/extent of sensory and trophic changes in the referred
      area. Five groups of subjects were studied, with: symptomatic gallbladder
      calculosis (3-20 colics); asymptomatic calculosis; symptomatic gallbladder shape
      abnormality (8-18 colics); asymptomatic shape abnormality; normal gallbladder/no
      symptoms. At the cystic point (CP) and contralaterally, all underwent measurement
      of: pain thresholds to electrical stimulation of skin, subcutis and muscle;
      thickness of subcutis and muscle via ultrasounds. Contralaterally to CP, all
      thresholds were not significantly different in the five groups. At CP, subcutis
      and muscle thresholds were significantly lower in symptomatic vs asymptomatic
      patients and/or normals (0.0001<P< 0.05). In symptomatic cases, at CP compared to
      contralaterally, subcutis and muscle thresholds were significantly lower
      (0.0001<P<0.02), subcutis thickness was significantly higher and muscle thickness
      significantly lower (0.006<P<0.02). Subcutis and muscle thresholds at CP in
      symptomatic patients were significantly and inversely correlated linearly to the
      number of colics (P<0.0004; P<0.0001). Patients with symptomatic calculosis were
      re-evaluated after 6 months; those not presenting further colics showed a
      significant increase in subcutis and muscle thresholds at CP, while those who
      continued presenting colics showed a further significant threshold decrease
      (0.01<P<0.05); tissue thickness did not vary. Referred hyperalgesia and altered
      trophism from the gallbladder only occur in painful pathology, their extent being
      modulated by the amount of perceived pain. The results suggest different
      mechanisms by which visceral nociceptive inputs trigger sensory vs trophic
      changes in the referred area.

PMID- 15733651
TI  - Dot-probe evaluation of selective attentional processing of pain cues in patients
      with chronic headaches.
AB  - Evidence supporting the notion that patients with chronic pain are characterized
      by attentional biases for sensory and affect pain words, and that such biases are
      mediated by fear of pain, is mixed. The present investigation was an attempt to
      replicate and extend initial findings obtained with the dot-probe task. Thirty
      patients with chronic headache and 19 healthy controls were tested using a dot
      probe task including affect pain, sensory pain, and neutral words. Individual
      difference variables, including fear of pain measures, were assessed and
      considered in analyses. Selective attention was denoted using the bias index,
      congruency index, and incongruency index. There were no significant between-group
      differences or interactions between group and word type observed for any of the
      indices of selective attention. Across groups there was evidence for a
      significant association between anxiety sensitivity and the bias index for
      sensory pain words, and between affective description of current pain and the
      incongruency index for affect pain words. These results do not provide convincing
      evidence that patients with chronic headache selectively attend to affect or
      sensory pain cues when compared to healthy controls. The significant cross-groups
      associations between anxiety sensitivity and current pain description and indices
      of selective attention are consistent with the notion that attentional biases may
      be influenced by fear propensity and current concerns. Implications of the
      findings and future research directions are discussed.

PMID- 15733652
TI  - Lack of estrogen increases pain in the trigeminal formalin model: a behavioural
      and immunocytochemical study of transgenic ArKO mice.
AB  - In order to examine the effect of estrogen on facial pain, we first compared the
      face-rubbing evoked by a formalin injection in the lip of aromatase-knockout
      (ArKO) mice, lacking endogenous estrogen production, 17 beta-estradiol-treated
      ArKO mice (ArKO-E2) and wild-type (WT) littermates. During the 'acute' phase of
      pain the time spent rubbing was similar in the three groups, whereas during the
      following 'interphase' and the second phase of pain, grooming was increased in
      ArKO mice. Estradiol-treatment restored a behaviour similar to WT group. To
      better understand estrogens modulation on pain processes, we examined changes in
      5-HT and CGRP innervations of trigeminal nucleus caudalis (TNC) in ArKO, ArKO-E2
      and WT groups sacrificed during the interphase. Whereas serotonin and CGRP
      immunoreactivities were comparable in WT and ArKO non-injected control groups,
      our data showed that 9 min after formalin injection, the density of
      serotoninergic terminals increased significantly in WT, but not in ArKO mice,
      while that of CGRP-immunoreactive fibers was lower in WT than in ArKO mice on the
      injected side. Estradiol-treatment only partially reversed these changes in ArKO
      E2 mice. We conclude that estrogen deprivation in ArKO mice can be responsible
      for increased nociceptive response and that it is accompanied by transmitter
      changes favouring pro- over anti-nociceptive mechanisms in TNC during interphase
      of the formalin model. That estradiol-treatment completely reverses the
      behavioural abnormality suggests that estrogens absence produces chiefly
      functional activation-dependent changes. However, the fact that the
      immunohistochemical abnormalities were not totally normalized by estradiol
      treatment suggested that some permanent developmental alterations may occur in
      ArKO mice.

PMID- 15733654
TI  - A normative analysis of the development of pain-related vocabulary in children.
AB  - Effective verbalization of pain requires progressive cognitive development and
      acquisition of social communication skills. Use of self-report in pediatric pain
      assessment assumes children have acquired a capacity to understand and use common
      words to describe pain. The current investigation documented the language most
      commonly used by young children to describe pain and the age of onset of use of
      these words. Two complementary research methodologies were employed. Study 1 used
      the CHILDES database, an aggregated transcript database of multiple research
      studies examining spontaneous speech development across childhood. Transcripts of
      14 randomly selected studies, yielding a total of 245 child participants ranging
      in age from 1 to 9 years, were searched for seven English primary pain word
      stems: 'ache', 'boo-boo', 'hurt', 'ouch', 'ow', 'pain', and 'sore'. Study 2
      surveyed 111 parents of children aged 3 to 6 years old concerning words the
      children commonly used for pain. Parents rated their children's frequency and age
      of first use of the seven pain word-stems. Both studies indicated that the most
      frequently used word-stems were 'hurt', 'ouch', and 'ow'. These words first
      emerged in children's vocabularies as early as 18 months of age. The word-stem
      'pain' was used relatively infrequently and gradually emerged in children's
      vocabularies. The findings indicate that young children rely on a select number
      of words to describe pain, with these words appearing in children's vocabularies
      at an early age. These results have implications for developmentally appropriate
      pain assessment in young children.

PMID- 15733653
TI  - Thiamine, pyridoxine, cyanocobalamin and their combination inhibit thermal, but
      not mechanical hyperalgesia in rats with primary sensory neuron injury.
AB  - Neuropathic pain after nerve injury is severe and intractable, and current drugs
      and nondrug therapies offer substantial pain relief to no more than half of
      affected patients. The present study investigated the analgesic roles of the B
      vitamins thiamine (B1), pyridoxine (B6) and cyanocobalamin (B12) in rats with
      neuropathic pain caused by spinal ganglia compression (CCD) or loose ligation of
      the sciatic nerve (CCI). Thermal hyperalgesia was determined by a significantly
      shortened latency of foot withdrawal to radiant heat, and mechanical hyperalgesia
      was determined by a significantly decreased threshold of foot withdrawal to von
      Frey filaments stimulation of the plantar surface of hindpaw. Results showed that
      (1) intraperitoneal injection of B1 (5, 10, 33 and 100 mg/kg), B6 (33 and 100
      mg/kg) or B12 (0.5 and 2 mg/kg) significantly reduced thermal hyperalgesia; (2)
      the combination of B1, B6 and B12 synergistically inhibited thermal hyperalgesia;
      (3) repetitive administration of vitamin B complex (containing B1/B6/B12
      33/33/0.5 mg/kg, for 1 and 2 wk) produced long-term inhibition of thermal
      hyperalgesia; and (4) B vitamins did not affect mechanical hyperalgesia or normal
      pain sensation, and exhibited similar effects on CCD and CCI induced
      hyperalgesia. The present studies demonstrate effects of B vitamins on pain and
      hyperalgesia following primary sensory neurons injury, and suggest the possible
      clinical utility of B vitamins in the treatment of neuropathic painful conditions
      following injury, inflammation, degeneration or other disorders in the nervous
      systems in human beings.

PMID- 15733655
TI  - Neurotensin activation of the NTR1 on spinally-projecting serotonergic neurons in
      the rostral ventromedial medulla is antinociceptive.
AB  - Microinjection of neurotensin (NT) in the rostral ventromedial medulla (RVM)
      produces dose-dependent antinociception. The NTR1 (Neurotensin Receptor Subtype
      1) may mediate part of this response, however definitive evidence is lacking, and
      the spinal mediators of NTR1-induced antinociception are unknown. In the present
      study, we used immunohistochemical techniques to show that the NTR1, but not the
      NTR2 is expressed by spinally projecting serotonergic neurons of the RVM. We also
      show that microinjection of NT or the NTR1-selective agonist PD149163 in the RVM
      both produce dose-dependent antinociception in the tail-flick test that is
      blocked by the NTR1-selective antagonist SR48692. The antinociception produced by
      NT or PD149163 is also blocked by intrathecal administration of the non-selective
      serotonergic receptor antagonist methysergide. The results of these experiments
      provide anatomical and behavioral evidence that activation of NTR1-expressing
      spinally projecting neurons in the RVM produces antinociception through release
      of serotonin in the spinal dorsal horn. These results support the conclusion that
      the NTR1 plays an important role in the central modulation of nociception.

PMID- 15733656
TI  - Widespread pain in fibromyalgia is related to a deficit of endogenous pain
      inhibition.
AB  - A deficit of endogenous pain inhibitory systems has been suggested to contribute
      to some chronic pain conditions, one of them being fibromyalgia. The aim of the
      investigation was to test whether endogenous pain inhibitory systems were
      activated by a spatial summation procedure in 30 fibromyalgia, 30 chronic low
      back pain, and 30 healthy volunteers who participated in a cross-over trial (two
      sessions). Each session consisted of visual analog scale ratings of pain during
      the immersion of different surfaces of the arm in circulating noxious cold (12
      degrees C) water. The arm was arbitrarily divided into eight segments from the
      fingertips to the shoulder. One session was ascending (from the fingertips to the
      shoulder) and the other was descending (from the shoulder to the fingertips);
      they included eight consecutive 2-min immersions separated by 5-min resting
      periods. For healthy and low back pain subjects, pain was perceived differently
      during the ascending and descending sessions (P=0.0001). The descending session
      resulted in lower pain intensity and unpleasantness. This lowering of the
      perception curve seems to be due to a full recruitment of inhibitory systems at
      the beginning of the descending session as opposed to a gradual recruitment
      during the ascending session. For fibromyalgia subjects, no significant
      differences were found between the increasing and decreasing sessions (P>0.05).
      These data support a deficit of endogenous pain inhibitory systems in
      fibromyalgia but not in chronic low back pain. The treatments proposed to
      fibromyalgia patients should aim at stimulating the activity of those endogenous
      systems.

PMID- 15733657
TI  - Can words hurt? Patient-provider interactions during invasive procedures.
AB  - Patients are often prepared for procedural discomforts with descriptions of pain
      or undesirable experiences. This practice is thought to be compassionate and
      helpful, but there is little data on the effect of such communicative behavior.
      This study assesses how such descriptions affect patients' pain and anxiety
      during medical procedures. The interactions of patients with their healthcare
      providers during interventional radiological procedures were videotaped during a
      previously reported 3-arm prospective randomized trial assessing the efficacy of
      self-hypnotic relaxation. One hundred and fifty-nine videos of the standard care
      and attention control arms were reviewed. All statements that described painful
      or undesirable experiences as warning before potentially noxious stimuli or as
      expression of sympathy afterwards were recorded. Patients' ratings of pain and
      anxiety on 0-10 numerical scales (0=No Pain, No Anxiety at All and 10=Worst Pain
      Possible, Terrified) after the painful event and/or sympathizing statement were
      the basis for this study. Warning the patient in terms of pain or undesirable
      experiences resulted in greater pain (P<0.05) and greater anxiety (P<0.001) than
      not doing so. Sympathizing with the patient in such terms after a painful event
      did not increase reported pain, but resulted in greater anxiety (P<0.05).
      Contrary to common belief, warning or sympathizing using language that refers to
      negative experiences may not make patients feel better. This conclusion has
      implications for the training in medical communication skills and suggests the
      need for randomized trials testing different patient-practioner interactions.

PMID- 15733658
TI  - Mouse ovary developmental RNA and protein markers from gene expression profiling.
AB  - To identify genes involved in morphogenetic events during mouse ovary
      development, we started with microarray analyses of whole organ RNA. Transcripts
      for 60% of the 15,000 gene NIA panel were detected, and about 2000 were
      differentially expressed in nascent newborn compared to adult ovary. Highly
      differentially expressed transcripts included noncoding RNAs and newly detected
      genes involved in transcription regulation and signal transduction. The phased
      pattern of newborn mouse ovary differentiation allowed us to (1) extend
      information on activity and stage specificity of cell type-specific genes; and
      (2) generate a list of candidate genes involved in primordial follicle formation,
      including podocalyxin (Podxl), PDGFR-beta, and a follistatin-domain-encoding gene
      Flst1. Oocyte-specific transcripts included many (e.g., Deltex2, Bicd2, and
      Zfp37) enriched in growing oocytes, as well as a novel family of untranslated
      RNA's (RLTR10) that is selectively expressed in early stage follicles. The
      results indicate that global expression profiling of whole organ RNA provides
      sensitive first-line information about ovarian histogenesis for which no in vitro
      cell models are currently available.

PMID- 15733659
TI  - Spatiotemporal characteristics and mechanisms of intracellular Ca(2+) increases
      at fertilization in eggs of jellyfish (Phylum Cnidaria, Class Hydrozoa).
AB  - We have clarified, for the first time, the spatiotemporal patterns of
      intracellular Ca(2+) increases at fertilization and the Ca(2+)-mobilizing
      mechanisms in eggs of hydrozoan jellyfish, which belong to the evolutionarily old
      diploblastic phylum, Cnidaria. An initial Ca(2+) increase just after
      fertilization took the form of a Ca(2+) wave starting from one cortical region of
      the egg and propagating to its antipode in all of four hydrozoan species tested:
      Cytaeis uchidae, Cladonema pacificum, Clytia sp., and Gonionema vertens. The
      initiation site of the Ca(2+) wave was restricted to the animal pole, which is
      known to be the only area of sperm-egg fusion in hydrozoan eggs, and the wave
      propagating velocity was estimated to be 4.2-5.9 mum/s. After a Ca(2+) peak had
      been attained by the initial Ca(2+) wave, the elevated Ca(2+) gradually declined
      and returned nearly to the resting value at 7-10 min following fertilization.
      Injection of inositol 1,4,5-trisphosphate (IP(3)), an agonist of IP(3) receptors
      (IP(3)R), was highly effective in inducing a Ca(2+) increase in unfertilized
      eggs; IP(3) at a final intracellular concentration of 12-60 nM produced a fully
      propagating Ca(2+) wave equivalent to that observed at fertilization. In
      contrast, a higher concentration of cyclic ADP-ribose (cADPR), an agonist of
      ryanodine receptors (RyR), only generated a localized Ca(2+) increase that did
      not propagate in the egg. In addition, caffeine, another stimulator of RyR, was
      completely without effect. Sperm-induced Ca(2+) increases in Gonionema eggs were
      severely affected by preinjection of heparin, an inhibitor of Ca(2+) release from
      IP(3)R. These results strongly suggest that there is a well-developed IP(3)R-,
      but not RyR-mediated Ca(2+) release mechanism in hydrozoan eggs and that the
      former system primarily functions at fertilization. Our present data also
      demonstrate that the spatial characteristics and mechanisms of Ca(2+) increases
      at fertilization in hydrozoan eggs resemble those reported in higher
      triploblastic animals.

PMID- 15733661
TI  - Caenorhabditis elegans germline patterning requires coordinated development of
      the somatic gonadal sheath and the germ line.
AB  - Interactions between the somatic gonad and the germ line influence the
      amplification, maintenance, and differentiation of germ cells. In Caenorhabditis
      elegans, the distal tip cell/germline interaction promotes a mitotic fate and/or
      inhibits meiosis through GLP-1/Notch signaling. However, GLP-1-mediated signaling
      alone is not sufficient for a wild-type level of germline proliferation. Here, we
      provide evidence that specific cells of the somatic gonadal sheath lineage
      influence amplification, differentiation, and the potential for tumorigenesis of
      the germ line. First, an interaction between the distal-most pair of sheath cells
      and the proliferation zone of the germ line is required for larval germline
      amplification. Second, we show that insufficient larval germline amplification
      retards gonad elongation and thus delays meiotic entry. Third, a more severe
      delay in meiotic entry, as is exhibited in certain mutant backgrounds,
      inappropriately juxtaposes undifferentiated germ cells with cells of the proximal
      sheath lineage, leading to the formation of a proximal germline tumor derived
      from undifferentiated germ cells. Tumors derived from dedifferentiated germ
      cells, however, respond to the proximal interaction differently depending on the
      mutant background. Our study underscores the importance of strict developmental
      coordination between neighboring tissues. We discuss these results in the context
      of mechanisms that may underlie tumorigenesis.

PMID- 15733662
TI  - Bone marrow contribution to skeletal muscle: a physiological response to stress.
AB  - Adult bone marrow-derived stem cells (BMDC) have been shown to contribute to
      numerous tissues after transplantation into a new host. However, whether the
      participation of these cells is part of the normal response to injury remains a
      matter of debate. Using parabiotically joined pairs of genetically labeled and
      wildtype mice, we show here that irradiation-induced damage of the target tissue,
      injection of bone marrow into the circulation, and immunological perturbation
      that are consequences of bone marrow transplantation are not necessary for bone
      marrow contribution to myofibers. Moreover, severe toxin-induced damage is not a
      prerequisite, as BMDC contribution to muscle is enhanced in response to increased
      muscle activity resulting from muscle overloading or forced exercise. Indeed,
      these two forms of muscle stress result in much more rapid contribution (within 1
      month) than voluntary running (6 months). These results indicate that BMDC
      contribute to myofibers in response to physiologic stresses encountered by
      healthy organisms throughout life.

PMID- 15733663
TI  - APC/C-Cdc20-mediated degradation of cyclin B participates in CSF arrest in
      unfertilized Xenopus eggs.
AB  - In vertebrates, unfertilized eggs are arrested at meiotic metaphase II (meta-II)
      by cytostatic factor (CSF), with Cdc2 activity maintained at a constant, high
      level. CSF is thought to suppress cyclin B degradation through the inhibition of
      the anaphase-promoting complex/cyclosome (APC/C)-Cdc20 while cyclin B synthesis
      continues in unfertilized eggs. Thus, it is a mystery how Cdc2 activity is kept
      constant during CSF arrest. Here, we show that the APC/C-Cdc20 can mediate cyclin
      B degradation in CSF-arrested Xenopus eggs and extracts, in such a way that when
      Cdc2 activity is elevated beyond a critical level, APC/C-Cdc20-dependent cyclin B
      degradation is activated and Cdc2 activity consequently declines to the critical
      level. This feedback control of Cdc2 activity is shown to be required for keeping
      Cdc2 activity constant during meta-II arrest. We have also shown that Mos/MAPK
      pathway is essential for preventing the cyclin B degradation from inactivating
      Cdc2 below the critical level required to sustain meta-II arrest. Our results
      indicate that under CSF arrest, Mos/MAPK activity suppresses cyclin B
      degradation, preventing Cdc2 activity from falling below normal meta-II levels,
      whereas activation of APC/C-Cdc20-mediated cyclin B degradation at elevated
      levels of Cdc2 activity prevents Cdc2 activity from reaching excessively high
      levels.

PMID- 15733660
TI  - Precocious retinal neurons: Pax6 controls timing of differentiation and
      determination of cell type.
AB  - The transcription factor Pax6 plays a pivotal role in eye development, as eye
      morphogenesis is arrested at a primitive optic vesicle stage in homozygous Pax6
      mutant mouse embryos. The arrested optic vesicle development has led to the
      assumption that cellular differentiation programs are unable to initiate.
      Contrary to this, we found that neurogenesis in Pax6 mutant optic vesicles was
      not arrested, but instead accelerated as numerous neurons differentiated
      precociously, more than a day earlier than normal. To identify potential
      mechanisms for Pax6 repression of neuron differentiation, we examined retinal
      proliferation and differentiation. Mutant optic vesicles had reduced
      proliferation, coupled with precocious activation of the proneural gene, Mash1.
      Ectopic expression of Mash1 was sufficient to induce precocious neuron
      differentiation. Subsequently, precocious neurons adopted a generic rather than a
      specific retinal neuron fate. Thus, Pax6 regulates the timing of retinal
      neurogenesis and couples it with specific neuron differentiation programs.

PMID- 15733664
TI  - Sonic hedgehog and retinoic acid are not sufficient to induce motoneuron
      generation in the avian caudal neural tube.
AB  - The caudal neural tube (CNT) of the avian embryo is devoid of both dorsal and
      ventral roots. We show that the lack of ventral roots in the CNT, from somite 48
      caudalwards, is due to an absence of post-mitotic motoneurons (MNs). The absence
      of MNs is not due to a defective notochordal induction since Sonic Hedgehog (SHH)
      signaling is intact and the caudal notochord is able to induce ectopic MNs when
      grafted laterally to a host neural tube. The transcription factors involved in MN
      specification (Pax6, Nkx6.1, and Olig2) are all expressed in the CNT, despite the
      lower expression level of Pax6, but an overlap between Olig2 and the ventrally
      expressed transcription factor Nkx2.2 is observed in the CNT. Grafting a quail
      CNT into the cervical level of a chick host rescues MN generation, demonstrating
      both the CNT potential for MN generation and the key role of the caudal
      environment in the MN differentiation blockade. The transplantation of the CNT
      flanking somites into the cervical level does not inhibit MN generation.
      Furthermore, implantation of a retinoic-acid-soaked bead laterally to the CNT
      does not rescue MN generation. Together, these data indicate that the rostral
      environment contains a signal different from both SHH and Retinoic Acid that acts
      on MN differentiation.

PMID- 15733665
TI  - Inactivation of tensin3 in mice results in growth retardation and postnatal
      lethality.
AB  - Tensin family is a group of focal adhesion proteins that interact with integrins,
      actin, and phosphotyrosine-containing proteins. To explore the in vivo functions
      of a new member of the family, tensin3, we have generated mutant mice with a
      disrupted tensin3 gene. Inactivation of tensin3 resulted in growth retardation
      and postnatal lethality in one third of the homozygous mutants. Histological
      analysis of those mutants showed incomplete development of the small intestine,
      lung, and bone. Villus formation in the small intestine was affected and cells
      migrated slower in the runt mutants. Their lungs also displayed enlarged air
      space suggesting defects in alveogenesis. In addition, the resting zone was
      thicker and fewer proliferating cells were present in the growth plates of
      tensin3(-/-) tibiae. These observations indicate that tensin3 is essential for
      normal development and functions of the small intestine, lung, and bone. These
      phenotypes of the runt tensin3(-/-) mice are similar to some clinical features of
      Silver-Russell syndrome (SRS) which is a genetically inherited defect. About 10%
      of SRS cases have been linked to abnormality in chromosome 7p11.2-13, where human
      tensin3 gene is located, suggesting a potential link between tensin3 and SRS.

PMID- 15733667
TI  - Proximodistal patterning during limb regeneration.
AB  - Regeneration is an ability that has been observed extensively throughout metazoan
      phylogeny. Amongst vertebrates, the urodele amphibians stand out for their
      exceptional capacity to regenerate body parts such as the limb. During this
      process, only the missing portion of the limb is precisely replaced--amputation
      in the upper arm results in regeneration of the entire limb, while amputation at
      the wrist produces a hand. Limb regeneration occurs through the formation of a
      local proliferative zone called the blastema. Here, we examine how proximodistal
      identity is established in the blastema. Using cell marking and transplantation
      experiments, we show that distal identities have already been established in the
      earliest stages of blastemas examined. Transplantation of cells into new
      environments is not sufficient to respecify cell identity. However,
      overexpression of the CD59, a cell surface molecule previously implicated in
      proximodistal identity during limb regeneration, causes distal blastema cells to
      translocate to a more proximal location and causes defects in the patterning of
      the distal elements of the regenerate. We suggest a model for the limb
      regeneration blastema where by 4 days post-amputation the blastema is already
      divided into distinct growth zones; the cells of each zone are already specified
      to give rise to upper arm, lower arm, and hand.

PMID- 15733666
TI  - Normal patterning of the coronary capillary plexus is dependent on the correct
      transmural gradient of FGF expression in the myocardium.
AB  - The formation of the coronary vessel system is vital for heart development, an
      essential step of which is the establishment of a capillary plexus that displays
      a density gradient across the myocardial wall, being higher on the epicardial
      than the endocardial side. This gradient in capillary plexus formation develops
      concurrently with transmural gradients of myocardium-derived growth factors,
      including FGFs. To test the role of the FGF expression gradient in patterning the
      nascent capillary plexus, an ectopic FGF-over-expressing site was created in the
      ventricular myocardial wall in the quail embryo via retroviral infection from E2
      2.5, thus abolishing the transmural gradient of FGFs. In FGF virus-infected
      regions of the ventricular myocardium, the capillary density across the
      transmural axis shifted away from that in control hearts at E7. This FGF-induced
      change in vessel patterning was more profound at E12, with the middle zone
      becoming the most vascularized. An up-regulation of FGFR-1 and VEGFR-2 in
      epicardial and subepicardial cells adjacent to FGF virus-infected myocardium was
      also detected, indicating a paracrine effect on induction of vascular signaling
      components in coronary precursors. These results suggest that correct transmural
      patterning of coronary vessels requires the correct transmural expression of FGF
      and, therefore, FGF may act as a template for coronary vessel patterning.

PMID- 15733668
TI  - Ephrin-As play a rhombomere-specific role in trigeminal motor axon projections in
      the chick embryo.
AB  - In this study, we investigate the possible role of ephrin-Eph signaling in
      trigeminal motor axon projections. We find that EphA receptors are expressed at
      higher levels by rhombomere 2 (r2) trigeminal motor neurons than by r3 trigeminal
      motor neurons in the chick embryo. Mapping of rhombomere-specific axon
      projections shows that r2 and r3 trigeminal motor neurons project to different
      muscle targets, including the mandibular adductor and the intermandibularis
      muscles respectively. Ephrin-A5 is expressed in these muscles, especially in some
      regions of the intermandibularis muscle, and can cause growth cone collapse of
      both r2 and r3 motor axons in vitro. We demonstrate that in vivo overexpression
      of ephrin-A5 in the intermandibularis muscle, or overexpression of dominant
      negative EphA receptors in trigeminal motor neurons leads to a reduction in
      branching of r3-derived motor axons specifically. Overexpression of full-length
      EphA receptors impairs the formation of r3 projections to the intermandibularis
      muscle. These findings indicate that ephrins and their Eph receptors play a role
      in trigeminal motor axon topographic mapping and in rhombomere 3-derived
      projections in particular.

PMID- 15733669
TI  - Human cytotrophoblasts acquire aneuploidies as they differentiate to an invasive
      phenotype.
AB  - Through an unusual differentiation process, human trophoblast progenitors
      (cytotrophoblasts) give rise to tumor-like cells that invade the uterus. By an
      unknown mechanism, invasive cytotrophoblasts exhibit permanent cell cycle
      withdrawal. Here, we report molecular cytogenetic data showing that approximately
      20 to 60% of these interphase cells had acquired aneusomies involving chromosomes
      X, Y, or 16. The incidence positively correlated with gestational age and
      differentiation to an invasive phenotype. Scoring 12 chromosomes in flow-sorted
      cytotrophoblasts showed that more than 95% of the cells were hyperdiploid. Thus,
      aneuploidy appears to be an important component of normal placentation, perhaps
      limiting the proliferative and invasive potential of cytotrophoblasts within the
      uterus.

PMID- 15733670
TI  - A concerted action of a paired-type homeobox gene, aristaless, and a homolog of
      Hox11/tlx homeobox gene, clawless, is essential for the distal tip development of
      the Drosophila leg.
AB  - The subdivision of the developing field by region-specific expression of genes
      encoding transcription factors is an essential step during appendage development
      in arthropod and vertebrates. In Drosophila leg development, the distal-most
      region (pretarsus) is specified by the expression of homeobox genes, aristaless
      and Lim1, and its immediate neighbor (distal tarsus) is specified by the
      expression of a pair of Bar homeobox genes. Here, we show that one additional
      gene, clawless, which is a homolog of vertebrate Hox11/tlx homeobox gene family
      and formerly known as C15, is specifically expressed in the pretarsus and
      cooperatively acts with aristaless to repress Bar and possibly to activate Lim1.
      Similar to aristaless, the maximal expression of clawless requires Lim1 and its
      co-factor, Chip. Bar attenuates aristaless and clawless expression through Lim1
      repression. Aristaless and Clawless proteins form a complex capable of binding to
      specific DNA targets, which cannot be well recognized solely by Aristaless or
      Clawless.

PMID- 15733671
TI  - Transcriptional control and patterning of the pho-1 gene, an essential acid
      phosphatase expressed in the C. elegans intestine.
AB  - We have previously described an acid phosphatase enzyme, PHO-1, present at the
      lumenal surface of all but the anterior six cells of the Caenorhabditis elegans
      intestine. In the present paper, we identify the pho-1 structural gene, which
      encodes a histidine acid phosphatase showing highest similarity to human
      prostatic acid phosphatase. The pho-1 5'-flanking DNA is capable of directing
      reporter gene expression that is both gut specific, correctly timed and correctly
      "patterned", that is, not expressed in the gut anterior. Furthermore, this
      anterior-posterior patterning of pho-1 expression responds to the C. elegans Wnt
      pathway as if pho-1 is repressed (directly or indirectly) by high levels of the
      HMG effector protein POP-1. Transgenic analysis of the pho-1 promoter shows that
      gut expression is critically dependent on a single WGATAR site. The gut-specific
      GATA factor ELT-2 binds to this site in vitro and removal of ELT-2 from the
      embryo destroys expression of the pho-1 reporter. Thus, all our results indicate
      that pho-1 is a direct downstream target of ELT-2. Finally, the pho-1 loss-of
      function mutation shows an interesting and unexpected phenotype for a somatically
      expressed hydrolytic enzyme: loss of pho-1 causes arrest of the majority of
      embryos but this lethality is a maternal effect. We suggest that pho-1 is
      required by the maternal intestine to assimilate some nutrient or cleavage
      product that is subsequently provided to the next generation of embryos.

PMID- 15733672
TI  - Candidate downstream regulated genes of HOX group 13 transcription factors with
      and without monomeric DNA binding capability.
AB  - Hox genes encode transcription factors that regulate the morphogenesis of
      developing embryos. In mammals, knowledge of the genetic pathways, including the
      possible direct or indirect targets, regulated by HOX proteins is extremely
      limited. To identify the downstream genes regulated by posterior HOX proteins, we
      expressed HOXA13 in mouse embryonic fibroblasts lacking paralog group 13
      expression using a bicistronic HOXA13/EGFP retroviral vector. Microarray analysis
      identified 68 genes with significant, reproducible RNA expression changes (50
      activated; 18 repressed) in stable HOXA13-expressing cells. Genes with the GO
      annotation terms "extracellular matrix" and "basement membrane" were greatly
      overrepresented, and several were shown to be regulated by HOX proteins in other
      studies. Among the genes strongly activated by HOXA13 were Enpp2, a bifunctional
      enzyme known to modulate tumor and normal cell motility and which is expressed in
      precartilaginous condensations; Fhl1, a transcription factor implicated in muscle
      cell differentiation and development; and M32486, a putative integral membrane
      molecule expressed in the female reproductive tract. Expression differences in
      the HOXA13-expressing cells were confirmed for selected downstream genes using
      semi-quantitative RT-PCR, and in vivo coexpression with Hoxa13 in the limb
      interdigital mesenchyme was demonstrated for many. For two candidates, Igfbp4 and
      Fstl, interdigital limb bud expression was reduced in Hoxa13 mutants. To explore
      whether paralogous and nonparalogous HOX proteins could regulate the same genes,
      we created new HOX cell lines and examined the expression of selected genes
      identified by the HOXA13 screen. HOXD13 similarly activated/repressed 6 tested
      candidates, demonstrating that multiple downstream genetic pathways may be
      regulated by paralog HOX proteins. In contrast, HOXA9 was only able to repress
      expression of some gene targets. A HOXD13 mutant, HOXD13(IQN >)(AAA), incapable
      of monomeric DNA-binding, activated the expression of 5 HOXA13-upregulated genes;
      but was incapable of repressing the expression of Ngef and Casp8ap2. Our results
      suggest that HOX protein-protein interactions without direct HOX DNA-binding may
      play a larger role in HOX transcriptional regulation than generally assumed, and
      DNA-binding appears critical for repression.

PMID- 15733673
TI  - Sox9 and Nkx2.5 determine the pyloric sphincter epithelium under the control of
      BMP signaling.
AB  - The organs of the digestive tract are specified by coordinated signaling between
      the endoderm and mesoderm during development. These epithelial-mesenchymal
      interactions lead to the organ-specific morphogenesis and differentiation of
      regions along the gut tube. In this paper, we show that in the chick, the SRY
      related transcription factor Sox9 is a marker for the posterior gizzard. Viral
      misexpression of Sox9 in the gizzard mesoderm is sufficient to specify epithelium
      characteristic of the pyloric sphincter. Sox9 expression is normally limited to
      the region of the posterior gizzard under the regulation of BMP signaling from
      the adjacent midgut. Misexpression of an activated form of BMPR1b in the gizzard
      upregulates Sox9 expression, while the BMP antagonist noggin down-regulates Sox9
      expression in the gizzard mesoderm. Previously, Nkx2.5 was identified as a marker
      for the mesoderm of the pyloric sphincter. As with Sox9, BMP signaling appears to
      regulate Nkx2.5 and its ability to determine the pyloric epithelium. Despite
      these similarities, our evidence suggests that Sox9 and Nkx2.5 are regulated
      independently by BMP signaling, and act coordinately to specify the pyloric
      sphincter.

PMID- 15733674
TI  - The Tribolium columnar genes reveal conservation and plasticity in neural
      precursor patterning along the embryonic dorsal-ventral axis.
AB  - The Drosophila columnar genes are key regulators of neural precursor formation
      and patterning along the dorsal-ventral axis of the developing CNS and include
      ventral nerve cord defective (vnd), intermediate nerve cord defective (ind),
      muscle segment homeodomain (msh), and Epidermal growth factor receptor (Egfr). To
      investigate the evolution of neural pattern formation, we identified and
      determined the expression patterns of Tribolium vnd, ind, and msh, and found that
      they are expressed in the medial, intermediate, and lateral columns of the
      developing CNS, respectively, in patterns similar, but not identical, to their
      Drosophila orthologs. The pattern of Egfr activity suggests that the genetic
      regulatory mechanisms that initiate Tc-vnd expression are similar in Drosophila
      and Tribolium, whereas those that initiate Tc-ind have diverged. RNAi analyses of
      gene function show that Tc-vnd and Tc-ind promote the formation of medial and
      intermediate column neural precursors and that vnd-mediated repression of ind
      establishes the boundary between the medial and intermediate columns. These data
      suggest that columnar gene expression and function underlie neural pattern
      formation in Drosophila, Tribolium, and potentially all insects, but that subtle
      spatiotemporal differences in expression of these genes may produce species
      specific morphological differences.

PMID- 15733675
TI  - The role of Phox2B in chromaffin cell development.
AB  - Phox2B, a homeodomain transcription factor closely related to Phox2A, is
      expressed in peripheral and central noradrenergic neurons. In neural crest (NC)
      derivatives Phox2B is restricted to sympathetic and parasympathetic ganglia,
      enteric neurons, and adrenal and extraadrenal chromaffin cells. Similar to MASH
      1, Phox2B has been implicated in synchronizing pan-neuronal and catecholaminergic
      phenotype-specific aspects of neurogenesis. The role of Phox2B for the
      differentiation of the neuroendocrine NC derivatives, the adrenal medullary
      chromaffin cells, has not been explored. We have previously reported that in MASH
      1-deficient mice most chromaffin cells are arrested at the early neuroblast stage
      and lack catecholaminergic differentiation. We show now that in Phox2B
      knockout/lacZ knockin mice the maturation of presumptive chromaffin cells is
      arrested at an even earlier stage of development. The cells lack the
      catecholaminergic marker enzyme TH and fail to form a centrally located medulla.
      In contrast to MASH-1 (-/-) mice they do not express dHand, Phox2A, c-ret,
      neurofilament, neuron-specific tubulin, and NCAM and appear ultrastructurally
      more immature. Many of these cells die by apoptosis. Despite the complete lack of
      differentiation, few lacZ-positive adrenal cells can still be found at E16.5. We
      conclude that Phox2B regulates very early events in the differentiation of
      adrenal chromaffin cells distinct to steps, which essentially require MASH-1.

PMID- 15733676
TI  - Neuromancer Tbx20-related genes (H15/midline) promote cell fate specification and
      morphogenesis of the Drosophila heart.
AB  - The Tbx family of transcription factors are prominently expressed in the early
      cardiac primordium throughout the animal kingdom. Mutations in Tbx genes result
      invariably in defective formation and function of the heart, including congenital
      heart disease in humans. Similar to their vertebrate counterpart, the Drosophila
      Tbx20 gene pair, neuromancer1 (nmr1, FlyBase:H15) and neuromancer2 (nmr2,
      Flybase:mid), exhibits a dynamic expression pattern, including in all contractile
      myocardial cells. Deletion mutants of nmr1 combined with mesoderm-specific knock
      down of nmr2 exhibit phenotypes that suggest nmr is critical for correct
      specification of the cardiac progenitor populations as well as for morphogenesis
      and assembly of the contractile heart tube. Loss-of-nmr-function causes a switch
      in cell fates in the cardiogenic region, in that the progenitors expressing the
      homeobox gene even skipped (eve) are expanded accompanied by a corresponding
      reduction of the progenitors expressing the homeobox gene ladybird (lbe). As a
      result, the number of differentiating myocardial cells is severely reduced
      whereas pericardial cell populations are expanded. Conversely, pan-mesodermal
      expression of nmr represses eve, while causing an expansion of cardiac lbe
      expression, as well as ectopic mesodermal expression of the homeobox gene tinman.
      In addition, nmr mutants with less severe penetrance exhibit cell alignment
      defects of the myocardium at the dorsal midline, suggesting nmr is also required
      for cell polarity acquisition of the heart tube. In exploring the regulation of
      nmr, we find that the GATA factor Pannier is essential for cardiac expression,
      and acts synergistically with Tinman in promoting nmr expression. Moreover,
      reducing nmr function in the absence of pannier further aggravates the deficit in
      cardiac mesoderm specification. Taken together, the data suggest that nmr acts
      both in concert with and subsequent to pannier and tinman in cardiac
      specification and differentiation. We propose that nmr is another determinant of
      cardiogenesis, along with tinman and pannier.

PMID- 15733678
TI  - Publishing ethics and Public Health.

PMID- 15733679
TI  - New intelligence.

PMID- 15733677
TI  - X chromosome reactivation and regulation in cloned embryos.
AB  - Somatic cell nuclear transfer embryos exhibit extensive epigenetic abnormalities,
      including aberrant methylation and abnormal imprinted gene expression. In this
      study, a thorough analysis of X chromosome inactivation (XCI) was performed in
      both preimplantation and postimplantation nuclear transfer embryos. Cloned
      blastocysts reactivated the inactive somatic X chromosome, possibly in a gradient
      fashion. Analysis of XCI by Xist RNA and Eed protein localization revealed
      heterogeneity within cloned embryos, with some cells successfully inactivating an
      X chromosome and others failing to do so. Additionally, a significant proportion
      of cells contained more than two X chromosomes, which correlated with an
      increased incidence of tetraploidy. Imprinted XCI, normally found in
      preimplantation embryos and extraembryonic tissues, was not observed in
      blastocysts or placentae from later stage clones, although fetuses recapitulated
      the Xce effect. We conclude that, although SCNT embryos can reactivate, count,
      and inactivate X chromosomes, they are not able to regulate XCI consistently.
      These results illustrate the heterogeneity of epigenetic changes found in cloned
      embryos.

PMID- 15733680
TI  - Development of public health observatories in the UK, Ireland and Europe.
AB  - Public Health Observatories are a new phenomenon in the United Kingdom and
      Ireland. However, similar institutions have been operating in other countries for
      many years. The nature and development of PHOs in England, Wales, Scotland and
      Ireland are described, and how they are supporting the growing public health
      movement in Europe is considered.

PMID- 15733681
TI  - Building public health skills and capacity in the English regions.
AB  - Local public health departments have variable access to a public health
      intelligence function, and information skills are scarce. Public health
      observatories are supporting the development of professional standards for public
      health intelligence specialists and offer training opportunities for both defined
      public health specialists and generalist public health specialists. In addition
      observatories support public health practice through educational programmes in
      health impact assessment, health equity audit, public health intelligence, and
      the provision of toolkits and advice on methods. Observatories have a key role in
      supporting and developing networks, in particular public health analysts, and the
      use of interoperable websites is enhancing these opportunities.

PMID- 15733682
TI  - Public health indicators.
AB  - An indicator is a measure used to express the behaviour of a system or part of a
      system. Indicators are widely used in the public sector, and there is widespread
      use of indicators for performance management of public health. In this paper, we
      define some of the terms used in relation to indicators. We outline some of the
      most important issues around selection and construction of indicators, and we
      include criteria for developing or assessing indicators. Use of inappropriate
      indicators can be misleading and can result in negative consequences for public
      health, and we point out the potential for pitfalls. Some misinterpretation of
      indicators could be avoided by use of better methods of presentation than the
      familiar league table. We use the example of a funnel plot to show a method of
      summarising indicator data which avoids ranking, and allows rapid identification
      of areas functioning outside normal limits.

PMID- 15733683
TI  - Supporting health impact assessment in practice.
AB  - Health impact assessment (HIA) is a process that aims to predict potential
      positive and negative effects of project, programme or policy proposals on health
      and health inequalities. It is recommended by national government and
      internationally. Supporting health impact assessment is one of the roles of
      English Public Health Observatories. The few centres in England with accredited
      health impact training centres have inadequate resources to meet demand.
      Currently, the London Health Observatory is providing the bulk of the training
      nationally. Some Public Health Observatories are currently investigating the
      preferences for support of those commissioning or conducting health impact
      assessment within their regions. The availability of published guidance on how to
      conduct health impact assessments has increased substantially over the past few
      years. The Department of Health has funded a research project led by the London
      Health Observatory to develop advice for reviewing evidence for use in health
      impact assessment. Completed health impact assessments can be useful resources.
      Evaluation of the process and impact of health impact assessment is important in
      order to demonstrate its usefulness and to learn lessons for the future. The
      focus for Public Health Observatories is to train and support others to conduct
      health impact assessment according to good practice, rather than undertaking
      health impact assessments themselves. The aim is to create sufficient skilled
      capacity around the country to undertake health impact assessments. The London
      Health Observatory plans to share its support models and to roll out a train the
      trainer programme nationally to enable effective local delivery of their national
      health impact assessment programme.

PMID- 15733684
TI  - Assessing and communicating the health and judicial impact of alcohol use.
AB  - BACKGROUND: Alcohol consumption places an increasing burden on health services,
      criminal justice agencies and private industry throughout the UK. Despite a
      national strategy to tackle alcohol-related harm, there remains a lack of
      epidemiology on alcohol use and related harms at local levels. Utilising national
      data sources and existing research studies, Regional Public Health Observatories
      are appropriately placed to calculate such measures and examine their
      relationship with deprivation. METHODS: For the North West of England, borough
      and health locality data were extracted from national sources. Alcohol
      consumption utilised lifestyle survey data and estimates of related harm were
      calculated by applying existing alcohol attributable fractions to deaths,
      hospital episodes and crime data. Contribution of alcohol to reduction in life
      expectancy was also calculated and all measures were correlated with deprivation.
      RESULTS: For the North West, the annual burden of alcohol was estimated at over
      3700 deaths, 56,700 hospital episodes and 71,000 crimes. Annual alcohol-related
      death rates for men varied from 0.43 to 1.17 per 1000 between Local Authorities
      and there was a six-fold variation in alcohol-related crime rate between areas.
      For males, alcohol reduced life expectancy by more than five months in the area
      worst affected. For both sexes, more deprived areas had significantly higher
      levels of alcohol-related hospital episodes, crime, and contribution to reduced
      life expectancy. CONCLUSIONS: Alcohol-related harm requires urgent, multi-agency
      attention at local levels throughout the UK. Applying appropriate research
      methods to national data sources provides limited but valuable local measures of
      alcohol use and its impact on health and crime. Regional Public Health
      Observatories can facilitate partnership working through such provision of
      national intelligence tailored to support local and regional action. Application
      of these techniques also helps identify additional requirements for better local
      intelligence on health-related behaviours and the necessity for consistency
      across local health and behaviour surveys.

PMID- 15733686
TI  - Trends in dental caries prevalence in 12-year-old schoolchildren between 1976 and
      2001 in Bauru, Brazil.
AB  - OBJECTIVE: To evaluate the trends in dental caries prevalence in 12-year-old
      schoolchildren between 1976 and 2001 in Bauru, Brazil. Study design. An
      epidemiological survey was performed by trained, calibrated examiners by the same
      research group in 1976, 1984, 1990, 1995 and 2001, using the decayed, missing and
      filled teeth (DMFT) index. METHODS: Urban elementary schools were chosen because
      they provide a fair representation of the city's population in terms of socio
      economic status. The study included 261, 321, 253, 377 and 211 subjects from the
      same regions in 1976, 1984, 1990, 1995 and 2001, respectively. The prevalence of
      caries and the DMFT index were used. RESULTS: A remarkable decrease was seen in
      the DMFT index at age 12 (84.53%) between 1976 and 2001. The DMFT indices at age
      12 were 9.89, 7.01, 3.97, 4.13 and 1.53 in 1976, 1984, 1990, 1995 and 2001,
      respectively. The percentage of schoolchildren presenting with sound permanent
      teeth (DMFT = 0) increased from 0.40 to 45.50% between 1976 and 2001. Over the
      same period, the percentage of schoolchildren with six or more decayed teeth
      decreased from 86.99% to 5.21%. CONCLUSIONS: The phenomenon of dental caries
      polarization is already perceptible in Bauru, Brazil. The increase in the number
      of schoolchildren with sound permanent teeth (DMFT = 0) suggests that the dental
      health policy in Bauru has had a positive effect in children's dental health, and
      should therefore be considered for other cities.

PMID- 15733685
TI  - General practitioners' views on and referral to NHS smoking cessation services.
AB  - OBJECTIVES: Increasing the rate of smoking cessation remains a major public
      health goal. To help achieve this in the UK, National Health Service (NHS)
      smoking cessation services have been established to provide treatment for smokers
      wanting help with stopping. Referrals from general practitioners (GPs) are
      crucial to the success of these clinics. This study aimed to assess English GPs'
      self-reported interactions with, and attitudes towards, their local smoking
      cessation services. STUDY DESIGN: Postal survey assessing the attitudes of GPs in
      England towards, and formal interactions with, NHS smoking cessation services.
      METHODS: A questionnaire was posted to a random sample of 544 GPs in England
      (response rate 63%). GPs' self-reported interactions with smoking cessation
      services and their attitudes towards these clinics were assessed. GPs were also
      asked what factors determined whether they prescribed nicotine-replacement
      therapy (NRT) and Buproprion (Zyban), and what was the extent and nature of their
      smoking cessation interventions with their patients. RESULTS: Most GPs (94%)
      reported that they were aware of the specialist smoking cessation service in
      their area. Seventy percent of GPs supported the continuation of current funding
      for specialist smoking cessation services. Seventy percent reported that they
      referred patients to these services, and 55% had staff within their practices
      trained as community smoking cessation advisors. Most GPs (79%) reported
      'clinical need' as a determinant of whether they prescribed NRT/Zyban, and a few
      GPs cited 'budgetary constraints' as a factor (15%). Ninety-eight percent of GPs
      reported that they record smoking status when new patients join their practice,
      and they advise smokers to stop 'at least every now and then'. CONCLUSIONS: GPs
      support the existence and continuation of specialist smoking cessation services,
      and most reported that they refer patients to them. Virtually every GP reported
      that they record smoking status when new patients join their practice, and they
      advise smokers to stop 'at least every now and then'.

PMID- 15733687
TI  - Evaluation of a photo-poster on nurses' perceptions of teething problems in South
      western Nigeria.
AB  - BACKGROUND: Health problems commonly associated with the eruption of teeth in
      babies continue to pose problems in Nigeria. Even nurses who should be well
      informed have misconceived views. In order to enlighten mothers and healthcare
      workers on this issue, a photo-poster was developed as a health-education tool.
      The objective of this study was to assess the effect of the poster, displayed in
      the workplace for 18 months, on the knowledge, attitude and reported practice of
      nurses. The study also aimed to assess the outcome of the inclusion of the photo
      poster in training materials in a workshop setting. METHODS: The study was
      conducted in two parts. In the first part, 542 nurses working in children's units
      within the city of Ibadan, South-western Nigeria were selected using a stratified
      sampling technique. A questionnaire was used to gather information on their
      perceptions of teething problems at baseline. Photo-posters were displayed in the
      nurses' workplaces for 18 months, and a follow-up survey was conducted using the
      same questionnaire. In the second part of the study, two groups of nurses (n = 21
      and n = 18 nurses) working in similar healthcare facilities in Ibadan
      participated in two separate workshops. One workshop used the photo-poster in
      addition to the standard educational materials, and the other workshop did not.
      Percentage differences between pre- and postintervention responses to perceived
      health problems were calculated. Intervention effects were the differences
      between the percentage changes in the intervention (with poster) and comparison
      (without poster) groups. Statistical differences were determined by Chi-squared
      test or one-tailed t-test, as appropriate. RESULTS: Five hundred and forty-two
      nurses (519 female and 23 male) completed the questionnaire survey at baseline
      and 403 (371 female and 32 male) at follow-up. Their ages ranged between 23 and
      56 years, with the greatest percentage aged 25-40 years. At baseline, many
      respondents indicated that several of the listed health problems were a
      consequence of tooth eruption. After exposure to the posters at their workplace
      for 18 months, there were slight changes in their opinions but most were not
      statistically significant (P > 0.05). The use of posters in a workshop setting
      revealed percentage changes ranging from -11 to 61% for the different associated
      health problems. Many of these changes were statistically significant (P < 0.05).
      CONCLUSION: Displaying photo-posters in the workplace did little to change
      nurses' perceptions of teething problems; the posters had more influence when
      they were used in an instructional, interactive atmosphere. It is recommended
      that the use of photo-posters in health education for such culturally entrenched
      health issues should be accompanied by discussion of the same subject wherever
      possible.

PMID- 15733688
TI  - Readiness for school entry: a community survey.
AB  - This study assessed the development of 4-5-year-old children in an urban low
      income community in Sri Lanka, with the aim of investigating their readiness for
      formal education. A modified Denver developmental screening test was used to
      determine the presence of age-appropriate motor, cognitive (including language)
      and social skills in 295 children. Of these children, 17.8% were unable to
      perform more than 50% of the tasks correctly. Children with motor problems were
      more likely to have difficulties with cognitive tasks than children without motor
      problems. Children who attended preschool did significantly better in most tasks
      compared with those who did not. The level of maternal education did not show a
      direct association with the competencies of the children. This assessment
      schedule can be used as a quick screening method in the community for early
      recognition of children with the potential for learning problems in school.

PMID- 15733689
TI  - Waiting for elective surgery: a qualitative analysis and conceptual framework of
      the consequences of delay.

PMID- 15733690
TI  - Anthropometric indications and nutritional intake of women in the Vaal Triangle,
      South Africa.
AB  - OBJECTIVES: The main purpose of this study was to determine the anthropometric
      indications and nutritional intake of pregnant and lactating women in the Vaal
      Triangle (n = 431). DESIGN AND METHODS: A validated quantitative food frequency
      questionnaire was used in this study. Trained fieldworkers conducted interviews
      with the help of food models to estimate portion sizes. The anthropometric
      measurements included weight, height and body mass index (BMI). Blood samples
      were collected for determining iron status parameters. RESULTS: The 10 items
      consumed most frequently by pregnant women were, in descending order: fresh milk;
      tea; coffee; cold drinks; maize meal; fruit juice; bread; magou (non-alcoholic
      fermented maize drink); rice and sugar. For lactating women, the results were:
      fresh milk; tea; coffee; maize meal; cold drinks; magou; bread; yoghurt; rice and
      sugar. Daily intakes (mean +/- SD) for pregnant women were 8425.71 +/- 2279 kJ,
      73.18 +/- 23 g protein, 62.29 +/- 23.7 g fat, 292.45 +/- 72.2 g carbohydrate and
      9.74 +/- 3.8 mg iron. For lactating women, the intakes were 8511.94 +/- 2047 kJ,
      76.24 +/- 25 g protein, 61.95 +/- 22.3 g fat, 294.37 +/- 64.2 g carbohydrate and
      10.50 +/- 4.0 mg iron. The results of this study showed that most of the women
      (98%) resided in towns and 79.3% were unemployed. The majority of the sample
      population was overweight or obese (BMI> or = 25). CONCLUSIONS: The diets of the
      subjects consisted primarily of plant-based foods. Animal foods were scarce
      except for milk. Most of the items consumed were low in iron. IMPLICATIONS: Iron
      deficiency is partly induced by plant-based diets containing low levels of poorly
      bio-available iron. An assessment of dietary intake is required to aid in the
      development of relevant dietary guidelines for the sample population.

PMID- 15733691
TI  - Disability retirement among former employees at the construction of the Great
      Belt Link.
AB  - OBJECTIVE: To investigate incidences of disability retirement among men who had
      been employed at the construction of a large traffic link in Denmark, which
      involved long working hours and long distances between home and work place.
      METHODS: Men aged 20-54 years at baseline who had been engaged in the
      construction of the Great Belt Link (n = 5882) were followed-up for disability
      retirements from 1996 to 2000. Age-standardized incidence ratios (SIR) were
      calculated and compared with those of other construction workers (n = 117,157).
      All economically active men in Denmark were used as the standard population.
      RESULTS: The SIRs for the two groups were 2.29 (95% confidence intervals (CI):
      1.95-2.67) and 0.98 (95% CI: 0.93-1.03), respectively. CONCLUSIONS: The Great
      Belt construction workers had an elevated risk for disability retirement compared
      with other construction workers and with economically active men in general.

PMID- 15733692
TI  - Are HIV/AIDS services in Leeds, UK, able to meet the needs of asylum seekers?
AB  - BACKGROUND: The Yorkshire and Humberside region of England ranks second only to
      London for reception of those seeking asylum in the UK. Human immunodeficiency
      virus (HIV) prevalence amongst asylum seekers is likely to mirror that in the
      country of origin. In 2001, the city of Leeds received 1100 asylum seekers,
      including dependents. Many of these were from areas with high seroprevalence of
      HIV, and HIV-infected asylum seekers require medical and social support. Are the
      current services for HIV-infected persons in Leeds appropriate and adequate for
      this new patient group? Provision of sexual health services for this client group
      needs to be evaluated. OBJECTIVES: To determine whether existing HIV/acquired
      immunodeficiency syndrome (AIDS) services in Leeds meet the needs of HIV-positive
      asylum seekers. METHODS: This was a qualitative study using semi-structured
      interviews. Seven service providers and 14 HIV-positive patients at Leeds Centre
      for Sexual Health, six of whom were asylum seekers, took part in the study.
      RESULTS: Asylum seekers and UK residents were equally satisfied with HIV/AIDS
      services at Leeds Centre for Sexual Health. Other agencies such as the Health
      Access Team and Terrence Higgins Trust had different strengths that provided
      valuable support for this client group. Unmet needs of asylum seekers were
      identified, such as specialist services for torture victims and educational
      opportunities. In areas of asylum seeker dispersal with increased case loads,
      this methodology may inform development of client-centred care networks.

PMID- 15733693
TI  - A community-based integrated nutrition research programme to alleviate poverty:
      baseline survey.
AB  - BACKGROUND: The United Nation's Children Fund (UNICEF) has indicated that urban
      poverty is primarily found in squatter settlements. At present, 13.5% of all
      South African households live in informal settlements. The main hypothesis for
      this empirical study was that micromechanisms would not negatively influence
      food, nutrition and health of residents in an informal settlement in the Vaal
      Triangle, South Africa. This hypothesis was tested empirically against the UNICEF
      framework of the immediate, underlying and basic causes of malnutrition. The
      purpose of this study was to establish a situation analysis of children and women
      before designing any intervention. OBJECTIVES: The objectives covered in this
      paper include Phases I and II of the project, namely planning of the project and
      determining the demographic and health profile of the sample as part of a
      situation analysis. STUDY DESIGN: This is a community participatory project.
      After a strategic participatory planning workshop with stakeholders, a plan of
      operation document, guiding all field undertakings, was drawn up (Phase 1),
      followed by a cross-sectional baseline survey (Phase II), situation analysis
      (Phase III), and implementation of community-based intervention studies (Phase
      IV). Impact measurement will follow in Phase V. METHODS: After the planning
      meeting and obtaining consent, a pretested, structured demographic and health
      questionnaire was used to obtain data from 357 randomly selected households in an
      informal settlement. Data were statistically analysed for means and standard
      deviations. RESULTS: The findings of the workshop evaluation indicated that 100%
      of the participants (n = 34) agreed that a need existed for this project, 74% (n
      = 24) understood the relevance, and 64% (n = 22) realized the importance for
      sustainable community development. In the baseline survey, 89% of the respondents
      lived in zinc shacks with two rooms or less (32.2%), three or four rooms (41.5%)
      or four rooms or more (26.3%). The household size was six people or more (33%),
      five people (18.5%), four people (21.3%) and three people or less (27.2%). The
      unemployment rate was 94.2% for respondents and 80.1% for their partners. The
      majority of households (42.6%) had a monthly income of <R500 (71 US dollars). The
      major health problems observed were chronic coughing (42%) and headaches (50.4%).
      Death of a child under 5 years of age was reported by 27.7% of respondents, of
      which 34.8% were stillborn, over the previous 5 years. CONCLUSIONS: These
      findings confirmed that poverty and household food insecurity were major
      problems. As such, these results form the basis for planning and implementing
      sustainable community-based intervention projects to promote public health
      nutrition in the Vaal Triangle, South Africa. It is, however, important to ensure
      community participation during all phases of the project to ensure
      sustainability.

PMID- 15733695
TI  - Health protection: communicable disease, public health and infection control
      educational programmes--a case study from the UK.
AB  - The health protection (HP) landscape is changing. Issues related to infectious
      diseases in the context of global health are receiving the attention of world
      leaders and policy makers. In the UK, the national health policies resonate with
      such transformations, presenting a range of opportunities and challenges. The
      opportunities include the formation of a new national organisation dedicated to
      protecting the people's health and reducing the impact of infectious disease, the
      Health Protection Agency. The opportunities also include the opening of non
      medical specialists's pathways in public health. The challenges represent the
      limited number of centres offering infection control education; the hospital
      focus and bias of the courses; new, resurgent and emerging infections;
      globalisation and travel; bacterial resistance; vaccine safety and coverage;
      bioterrorism; global response capacity; and visa restrictions. Within this
      context, this paper presents a case study of a HP educational programme at a
      British university in the south of England. It outlines the course design and
      philosophy, participants, recruitment, aims, descriptions and learning outcomes.
      A range of teething problems associated with the initiation and running of such
      programmes is considered. These include aspects related to the university,
      features associated with the modules, characteristics of the students, and other
      interconnected larger scale international issues. Some suggestions for the way
      forward are presented. Collectively, attention to the suggested measures can
      ensure that the processes that teaching programmes embrace to refine their
      content and delivery will equip tomorrow's professionals with the requisite HP
      knowledge and skills.

PMID- 15733694
TI  - Multidrug resistance in Salmonella enterica serovar typhi isolated from patients
      with typhoid fever complications in Lagos, Nigeria.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of Salmonella
      enterica serovar typhi in patients with pyrexia of unknown origin (PUO), and
      antimicrobial resistance in strains isolated from patients with S. typhi in
      Lagos, Nigeria. STUDY DESIGN: In total, 103 patients were included in this study,
      subdivided into two categories. Category A comprised 74 patients presenting with
      PUO, and Category B comprised 29 patients harbouring S. typhi who did not respond
      to initial treatment. METHODS: Blood samples were cultured for bacterial isolates
      and identified by standard procedures. Susceptibility testing was performed
      according to the National Committee for Clinical Laboratory Standards. Plasmid
      DNA extraction was performed using the alkaline lysis method with Escherichia
      coli v517 used as the standard. Conjugation and transformation experiments were
      performed using standard methods. For the latter, E. coli K12 HB 101 (ara-14,
      galK2, hsd 520, lacyl, leu, mtl-1, Pro A2, rec A13, rps L20, sup E44, thii xyl-5)
      was used as the recipient and plasmid PBR 322 was used as the positive control.
      RESULTS: The prevalence of S. typhi in PUO was 16.2% (12/74). In all, 25 of 41
      (61.0%) cases were multidrug resistant (MDR) with phenotypic-resistant patterns:
      ACoCT, ACTCeS, ACTCoCe and ACTS were commonly encountered among the strains.
      Interestingly, four of the strains harbouring similar plasmid DNA were isolated
      from patients with hepatosplenomegaly, and a strain harbouring a large
      transferable plasmid of 81.2MDa was isolated from a psychosis patient.
      CONCLUSIONS: Our study confirmed the circulation of MDR S. typhi in Lagos,
      Nigeria. Periodic review of antibiotics used in hospitals is essential as the
      efficacies of chloramphenicol, ampicillin and cotrimoxazole are now doubtful.
      Ciprofloxacin and ofloxacin are effective drugs for treatment of typhoid fever,
      but with current trends of drug abuse in Nigeria, resistance is likely to
      develop. These results, therefore, provide an early warning signal for the
      prudent use of fluoroquinolone antimicrobials to preserve their usefulness.

PMID- 15733696
TI  - Safety concerns at the FDA.

PMID- 15733697
TI  - Disease is not a justification for discrimination.

PMID- 15733698
TI  - Stroke and nutrition: FOOD for thought.

PMID- 15733699
TI  - Mad cows and monkey business: the end of vCJD?

PMID- 15733700
TI  - Charging failed asylum seekers for health care in the UK.

PMID- 15733701
TI  - Do-not-resuscitate orders in the surgical setting.

PMID- 15733702
TI  - Research into care at the end of life.

PMID- 15733703
TI  - Intensive management of type 1 diabetes in young children.

PMID- 15733704
TI  - Global or Gaelic epidemic of hypothyroidism?

PMID- 15733707
TI  - Co-trimoxazole prophylaxis in African children with HIV-1.

PMID- 15733708
TI  - RCOG recommendations on hormone replacement therapy.

PMID- 15733710
TI  - Beyond deworming.

PMID- 15733711
TI  - Beyond deworming.

PMID- 15733712
TI  - Childhood cancer treatment in developing countries.

PMID- 15733714
TI  - Assessment of trends in childhood cancer incidence.

PMID- 15733715
TI  - A survival strategy for anatomy.

PMID- 15733716
TI  - Routine oral nutritional supplementation for stroke patients in hospital (FOOD):
      a multicentre randomised controlled trial.
AB  - BACKGROUND: Undernutrition is common in hospital patients with stroke, can
      develop or worsen in hospital, and is associated with poor outcomes. We aimed to
      establish whether routine oral nutritional supplements improve outcome after
      stroke. METHODS: The FOOD trials are a family of three pragmatic, multicentre,
      randomised controlled trials. We measured the outcomes of stroke patients who
      could swallow and who were randomly allocated normal hospital diet or normal
      hospital diet plus oral nutritional supplements until hospital discharge. The
      primary outcome was death or poor outcome (modified Rankin scale [MRS] grade 3
      5), 6 months after enrollment, measured unaware of treatment allocation. Analysis
      was by intention to treat. FINDINGS: Between Nov 1, 1996, and July 31, 2003, 4023
      patients were enrolled by 125 hospitals in 15 countries. Only 314 (8%) patients
      were judged to be undernourished at baseline. Vital status and MRS at the end of
      the trial were known for 4012 and 4004 patients, respectively. Supplemented diet
      was associated with an absolute reduction in risk of death of 0.7% (95% CI -1.4
      to 2.7) and an increased risk of death or poor outcome of 0.7% (-2.3 to 3.8).
      INTERPRETATION: We could not confirm the anticipated 4% absolute benefit for
      death or poor outcome from routine oral nutritional supplements for mainly well
      nourished stroke patients in hospital. Our results would be compatible with a 1%
      or 2% absolute benefit or harm from oral supplements. These results do not
      support a policy of routine oral supplementation after stroke.

PMID- 15733717
TI  - Effect of timing and method of enteral tube feeding for dysphagic stroke patients
      (FOOD): a multicentre randomised controlled trial.
AB  - BACKGROUND: Undernutrition is common in patients admitted with stroke. We aimed
      to establish whether the timing and route of enteral tube feeding after stroke
      affected patients' outcomes at 6 months. METHODS: The FOOD trials consist of
      three pragmatic multicentre randomised controlled trials, two of which included
      dysphagic stroke patients. In one trial, patients enrolled within 7 days of
      admission were randomly allocated to early enteral tube feeding or no tube
      feeding for more than 7 days (early versus avoid). In the other, patients were
      allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The
      primary outcome was death or poor outcome at 6 months. Analysis was by intention
      to treat. FINDINGS: Between Nov 1, 1996, and July 31, 2003, 859 patients were
      enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early
      tube feeding was associated with an absolute reduction in risk of death of 5.8%
      (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (
      4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were
      enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an
      absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an
      increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05).
      INTERPRETATION: Early tube feeding might reduce case fatality, but at the expense
      of increasing the proportion surviving with poor outcome. Our data do not support
      a policy of early initiation of PEG feeding in dysphagic stroke patients.

PMID- 15733718
TI  - Assessment of the efficacy and effectiveness of influenza vaccines in healthy
      children: systematic review.
AB  - BACKGROUND: We aimed to assess evidence of efficacy and effectiveness of live
      attenuated and inactivated influenza vaccines in children up to 16 years of age.
      METHODS: We searched the Cochrane Library, MEDLINE, EMBASE Biological Abstracts,
      and Science Citation Index to June, 2004, in any language, and contacted vaccine
      manufacturers and authors of relevant studies to identify additional data. We
      included randomised, cohort, and case-control studies comparing efficacy of
      vaccines against influenza (reduction in laboratory-confirmed cases),
      effectiveness of vaccines against influenza-like illness (reduction in
      symptomatic cases), or both, with placebo or no intervention. We analysed the
      following outcomes: influenza, influenza-like illness, admissions, school
      absences, complications, and secondary transmission. FINDINGS: We included 14
      randomised controlled trials, eight cohort studies, one case-control study, and
      one randomised controlled trial of intraepidemic use of the vaccines. Live
      attenuated influenza vaccines had 79% efficacy and 38% effectiveness in children
      older than 2 years compared with placebo or no immunisation. Inactivated vaccines
      had lower efficacy (65%) than live attenuated vaccines, and in children aged 2
      years or younger they had similar effects to placebo. Effectiveness of
      inactivated vaccines was about 28% in children older than 2 years. Vaccines were
      effective in reducing long school absences (relative risk 0.14 [95% CI 0.07
      0.27]). Studies assessing the effects of vaccines against secondary cases, lower
      respiratory tract disease, acute otitis media, and hospital stay suggested no
      difference with placebo or standard care, but lacked statistical power.
      INTERPRETATION: Influenza vaccines (especially two-dose live attenuated vaccines)
      are efficacious in children older than 2 years. Efficacy and effectiveness of the
      vaccines differed strikingly. Only two small studies assessed the effects of
      influenza vaccines on hospital admissions and no studies assessed reductions in
      mortality, serious complications, and community transmission of influenza. If
      influenza immunisation in children is to be recommended as public-health policy,
      large-scale studies assessing such important outcomes and undertaking direct
      comparisons of vaccines are urgently needed.

PMID- 15733719
TI  - Risk of oral infection with bovine spongiform encephalopathy agent in primates.
AB  - The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)-
      which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by
      incomplete knowledge about the efficiency of oral infection and the magnitude of
      any bovine-to-human biological barrier to transmission. We therefore investigated
      oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral
      dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like
      neurological disease 60 months after exposure, whereas the other remained free of
      disease at 76 months. On the basis of these findings and data from other studies,
      we made a preliminary estimate of the food exposure risk for man, which provides
      additional assurance that existing public health measures can prevent
      transmission of BSE to man.

PMID- 15733720
TI  - A target rash.

PMID- 15733721
TI  - Pre-eclampsia.
AB  - Pre-eclampsia is a major cause of maternal mortality (15-20% in developed
      countries) and morbidities (acute and long-term), perinatal deaths, preterm
      birth, and intrauterine growth restriction. Key findings support a causal or
      pathogenetic model of superficial placentation driven by immune maladaptation,
      with subsequently reduced concentrations of angiogenic growth factors and
      increased placental debris in the maternal circulation resulting in a (mainly
      hypertensive) maternal inflammatory response. The final phenotype, maternal pre
      eclamptic syndrome, is further modulated by pre-existing maternal cardiovascular
      or metabolic fitness. Currently, women at risk are identified on the basis of
      epidemiological and clinical risk factors, but the diagnostic criteria of pre
      eclampsia remain unclear, with no known biomarkers. Treatment is still prenatal
      care, timely diagnosis, proper management, and timely delivery. Many
      interventions to lengthen pregnancy (eg, treatment for mild hypertension, plasma
      volume expansion, and corticosteroid use) have a poor evidence base. We review
      findings on the diagnosis, risk factors, and pathogenesis of pre-eclampsia and
      the present status of its prediction, prevention, and management.

PMID- 15733722
TI  - Pre-eclampsia: a first hand account.

PMID- 15733723
TI  - Optimised glucocorticoid therapy: the sharpening of an old spear.
AB  - CONTEXT: Glucocorticoids are frequently and successfully used drugs that mediate
      important immunosuppressive and anti-inflammatory effects. These drugs are also
      relatively inexpensive, but it is their broad range of adverse reactions that
      continuously stimulate efforts to optimise glucocorticoid treatment. STARTING
      POINT: Last year, Mary Leonard and colleagues studied 60 children and adolescents
      with nephrotic syndrome intermittently treated with high-dose glucocorticoids (N
      Engl J Med 2004; 351: 868-75). The patients received an average of 23 g
      glucocorticoids and were significantly shorter, had a significantly greater body
      mass index, and the prevalence of obesity was significantly higher than in
      controls. The expected deficits in the bone-mineral content of the spine or whole
      body were not seen, although this finding could be attributed to the highly
      increased body-mass index of many of the patients. WHERE NEXT: Glucocorticoids
      are urgently needed to treat a wide range of diseases in children and adults.
      Therefore strategies such as preferred local application or fine-tuned dose
      regimens have been developed over the past five decades to improve the benefit
      risk ratio. However, these efforts with conventional glucocorticoid drugs seem to
      have almost reached their limits. A further improvement needs qualitatively new
      drugs, which are currently in the development pipeline, with the most promising
      being the nitrosoglucocorticoids (nitrosteroids) and selective glucocorticoid
      receptor agonists.

PMID- 15733724
TI  - Environmental tobacco smoke research published in the journal Indoor and Built
      Environment and associations with the tobacco industry.
AB  - In the late 1980s, the international tobacco industry assisted in the
      establishment of the International Society of the Built Environment, which
      published the journal Indoor and Built Environment. Using evidence from tobacco
      industry documents, we examine the industry associations of the Society's
      executive, the journal's editor and board, and the extent to which the journal
      publishes papers on environmental tobacco smoke that would be deemed favourable
      by the tobacco industry. The society's executive has been dominated by paid
      consultants to the tobacco industry: all six members in 1992 and seven of eight
      members in 2002 had financial associations through industry lawyers. 67% of the
      editorial board in 1992 and 66% in 2002 had histories of financial associations
      with the tobacco industry. 61% (40/66) of papers related to environmental tobacco
      smoke published in Indoor and Built Environment in the study period reached
      conclusions that could be judged to be industry-positive. Of these, 90% (36/40)
      had at least one author with a history of association with the tobacco industry.
      The executive of the International Society of the Built Environment and the
      editorial board of Indoor and Built Environment are in large part consisted of
      people with histories of consultancies to the tobacco industry. On the basis of
      the evidence presented in this paper, there is a serious concern the tobacco
      industry may have been unduly influential on the content of the journal.

PMID- 15733725
TI  - Focusing on improved water and sanitation for health.

PMID- 15733726
TI  - How much would poor people gain from faster progress towards the Millennium
      Development Goals for health?

PMID- 15733727
TI  - Ruptured abdominal aortic aneurysm.

PMID- 15733728
TI  - New developments in metabolic syndrome. Proceedings of the 1st Conference of the
      Paul Hamel Institute. 7-8 June 2004, Monaco.

PMID- 15733729
TI  - Regulatory role of peroxisome proliferator-activated receptor delta (PPAR delta)
      in muscle metabolism. A new target for metabolic syndrome treatment?
AB  - Peroxisome proliferator-activated receptors (PPARs) are transcription factors
      involved in both developmental and metabolic functions. There are activated by
      fatty acids, fatty acid metabolites, and synthetic compounds marketed for their
      lipid-lowering and antidiabetic actions. It was clearly established that
      activation of PPAR alpha and PPAR gamma, by fibrates and thiazolidinediones,
      respectively, impair metabolic disorders. The implication of the third member of
      the PPAR family, PPAR delta, remained evasive until recently. These past few
      years, it has been demonstrated that treatment with PPAR delta agonists
      normalizes blood lipids, reduces insulin resistance and adiposity in rodent and
      primate. Utilization of both cellular and animal models revealed that the nuclear
      receptor plays a central role in the control of fatty acid burning in adipose
      tissue and skeletal muscle. Furthermore, PPAR delta appeared to be important for
      adaptive response of skeletal muscle to environmental changes, such as physical
      exercise.

PMID- 15733730
TI  - PPAR gamma, 10 years later.
AB  - It is now over 10 years since the discovery of peroxisome proliferator activated
      receptor gamma (PPAR gamma) and its unique role in adipogenesis. The subsequent
      identification of PPAR gamma as the target of insulin sensitizing drugs certified
      this ligand-regulated transcription factor as an exciting link between adipocyte
      biology and peripheral insulin resistance. Here, I summarize the great progress
      that has been made over the past decade in elucidating the biology of PPAR gamma
      and its role in adipogenesis and glucose metabolism. Prospects for future
      research leading to new therapies for obesity and diabetes are also discussed.

PMID- 15733731
TI  - The metabolic syndrome and the hepatic fatty acid drainage hypothesis.
AB  - Much data indicates that lowering of plasma triglyceride levels by hypolipidemic
      agents is caused by a shift in the liver metabolism towards activation of
      peroxisome proliferator activated receptor (PPAR)alpha-regulated fatty acid
      catabolism in mitochondria. Feeding rats with lipid lowering agents leads to
      hypolipidemia, possibly by increased channeling of fatty acids to mitochondrial
      fatty acid oxidation at the expense of triglyceride synthesis. Our hypothesis is
      that increased hepatic fatty acid oxidation and ketogenesis drain fatty acids
      from blood and extrahepatic tissues and that this contributes significantly to
      the beneficial effects on fat mass accumulation and improved peripheral insulin
      sensitivity. To investigate this theory we employ modified fatty acids that
      change the plasma profile from atherogenic to cardioprotective. One of these
      novel agents, tetradecylthioacetic acid (TTA), is of particular interest due to
      its beneficial effects on lipid transport and utilization. These hypolipidemic
      effects are associated with increased fatty acid oxidation and altered energy
      state parameters of the liver. Experiments in PPAR alpha-null mice have
      demonstrated that the effects hypolipidemic of TTA cannot be explained by altered
      PPAR alpha regulation alone. TTA also activates the other PPARs (e.g., PPAR
      delta) and this might compensate for deficiency of PPAR alpha. Altogether, TTA
      mediated clearance of blood triglycerides may result from a lowered level of apo
      C-III, with a subsequently induction of hepatic lipoprotein lipase activity and
      (re)uptake of fatty acids from very low density lipoprotein (VLDL). This is
      associated with an increased hepatic capacity for fatty acid oxidation, causing
      drainage of fatty acids from the blood stream. This can ultimately be linked to
      hypolipidemia, anti-adiposity, and improved insulin sensitivity.

PMID- 15733732
TI  - The role of the orphan nuclear receptor Rev-Erb alpha in adipocyte
      differentiation and function.
AB  - Lipid and carbohydrate homeostasis in higher organisms is governed by an
      integrated system that has a capacity to rapidly respond to metabolic changes.
      Numerous signals reciprocally convey information about body fat status from the
      periphery to central nervous system in the attempt to maintain body weight nearly
      stable throughout life. The role of adipocyte in energy homeostasis extends its
      function as a simple energy storage cell. Indeed, adipose tissue not only
      secretes fatty acids, but is also an active endocrine and paracrine organ due to
      the production of secreted proteins and lipid indicators collectively called
      adipokines. These observations have spurred interest in the identification of the
      transcriptional and other regulatory pathways of adipocyte differentiation. The
      nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma)
      (NR1C3) and members of the CCAAT enhancer-binding protein (C/EBP) family are
      central mediators controlling adipocyte differentiation and function. Rev-erb
      alpha (NR1D1) is an orphan nuclear receptor encoded on the opposite strand of the
      thyroid receptor alpha gene. Rev-erb alpha acts as a negative regulator of
      transcription binding to the same response element than another orphan nuclear
      receptor, ROR alpha. Rev-erb alpha is highly expressed in adipose tissue,
      skeletal muscle, heart, liver and brain. Rev-erb alpha expression increases
      during adipocyte differentiation of 3T3-L1 cells and is induced by PPAR gamma
      activation in both 3T3-L1 cells in vitro and in rat adipose tissue in vivo via a
      direct repeat (DR2) in the Rev-erb alpha promoter. Ectopic expression of Rev-erb
      alpha potentiates the adipocyte differentiation in 3T3-L1 cells. Recent results
      in vascular smooth muscle cells (VSMCs) indicate that Rev-erb alpha also controls
      inflammation by regulating NF-kappa B responsive genes, such as IL-6 and COX-2.
      Future studies on a potential role of Rev-erb alpha on glucose homeostasis and/or
      inflammation control are thus warranted.

PMID- 15733733
TI  - Proposed involvement of adipocyte glyceroneogenesis and phosphoenolpyruvate
      carboxykinase in the metabolic syndrome.
AB  - Elevated concentration of plasma non-esterified fatty acids (NEFA) is now
      recognized as a key factor in the onset of insulin-resistance and type 2 diabetes
      mellitus. During fasting, circulating NEFAs arise from white adipose tissue (WAT)
      as a consequence of lipolysis from stored triacylglycerols. However, a
      significant part of these FAs (30-70%) is re-esterified within the adipocyte, so
      that a recycling occurs and net FA output is much less than << true >> lipolysis.
      Indeed, a balance between two antagonistic processes, lipolysis and FA re
      esterification, controls the rate of net FA release from WAT. During fasting, re
      esterification requires glyceroneogenesis defined as the de novo synthesis of
      glycerol-3-P from pyruvate, lactate or certain amino acids. The key enzyme in
      this process is the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK
      C; EC 4.1.1.32). Recent advance has stressed the role of glyceroneogenesis and of
      PEPCK-C in FA release from WAT. Results indicate that glyceroneogenesis is indeed
      important to lipid homeostasis and that a disregulation in this pathway may have
      profound pathophysiological effects. The present review focuses on the regulation
      of glyceroneogenesis and of PEPCK-C gene expression and activity by FAs, retinoic
      acids, glucocorticoids and the hypolipidemic class of drugs, thiazolidinediones.

PMID- 15733734
TI  - Phosphorylation of PPARs: from molecular characterization to physiological
      relevance.
AB  - In addition to their ligand-mediated activation, nuclear receptor activity is
      finely tuned by their phosphorylation status. PPARs are phosphorylated by several
      kinases (PKA, PKC, MAPKs, and AMPK), which affect their activity in a ligand
      dependent or -independent manner according to the isoform and cellular context.
      Molecular consequences are multiple, including changes in ligand affinity, DNA
      binding, recruitment of transcriptional cofactors, proteasome degradation...
      Finally, the physiological relevance of PPAR phosphorylation is discussed.

PMID- 15733735
TI  - Effects of testosterone on fat cell lipolysis. Species differences and possible
      role in polycystic ovarian syndrome.
AB  - Testosterone is a potent regulator of lipolysis by influencing catecholamine
      signal transduction in fat cells. Major species differences exist as regards the
      testosterone effect. In rodents testosterone increases beta-adrenergic receptor
      mediated signals to lipolysis at multiple steps in the lipolytic cascade. The sex
      hormone also increases alpha2-adrenoceptor antilipolytic signalling in hamster
      which unlike rat express this receptor in their fat cells. In humans the region
      of adipose tissue is critical. Visceral fat cell lipolysis is not responsive to
      testosterone but this sex hormone decreases catecholamine-induced lipolysis in
      subcutaneous fat cells due to inhibition of the expression of beta2-adrenoceptors
      and hormone sensitive lipase. In polycystic ovarian syndrome (PCOS), which is
      characterized as a hyperandrogenic state, the lipolytic effect of catecholamine
      is decreased in subcutaneous adipocytes due to low content of beta2-adrenoceptors
      and hormone sensitive lipase. It is possible that the increased testosterone
      levels are responsible for these abnormalities in catecholamine signal
      transduction in subcutaneous fat cells of PCOS women. However, in visceral fat
      cells of PCOS women catecholamine-induced lipolysis is enhanced which cannot be
      explained by testosterone.

PMID- 15733736
TI  - Role of PAT proteins in lipid metabolism.
AB  - One of the central reactions in bodily energy metabolism is lipolysis in
      adipocytes, the reaction that governs the release of stored fatty acids from the
      adipocyte triacylglycerol pool, which constitutes the major energy reserve in
      animals. These fatty acids are then transported by serum albumin to various
      tissues to supply their energy requirements. This reaction was previously thought
      to result from phosphorylation and activation of hormone-sensitive lipase by
      protein kinase A (PKA) but is now known to be governed by a translocation of the
      lipase from the cytosol to the surface of the intracellular lipid droplet that
      houses the reservoir of TAG. This droplet is coated with perilipin A, which is
      also phosphorylated by PKA in response to lipolytic stimuli, and phosphorylation
      of perilipin A is essential for HSL translocation and stimulated lipolysis.

PMID- 15733737
TI  - The role of MAPKs in adipocyte differentiation and obesity.
AB  - The ERK, p38 and JNK mitogen activated protein kinases (MAPKs) are intracellular
      signalling pathways that play a pivotal role in many essential cellular processes
      such as proliferation and differentiation. MAPKs are activated by a large variety
      of stimuli and one of their major functions is to connect cell surface receptors
      to transcription factors in the nucleus, which consequently triggers long-term
      cellular responses. This review focuses on their in vitro and in vivo roles in
      adipocyte differentiation and obesity. Hyperplasia of adipose tissue is a
      critical event for the development of obesity. Several studies have analysed the
      role of MAPKs in vitro in adipocyte differentiation of preadipocyte established
      cell lines. In the case of ERK, although the first data appeared contradictory, a
      consensus scenario arises: ERK would be necessary to initiate the preadipocyte
      into the differentiation process and, thereafter, this signal transduction
      pathway needs to be shut-off to proceed with adipocyte maturation. The limitation
      of these cellular models is that only terminal adipocyte differentiation can be
      analysed, eluding the early proliferative steps of adipogenesis. New insights are
      now emerging by investigations conducted either in vitro with the use of
      embryonic stem (ES) cells or in vivo with mice where these genes are invalidated.
      These studies not only confirm and/or precise the various functions of MAPKs in
      adipogenesis but, importantly, reveal unsuspected roles, for example JNK in
      obesity or ERK in adipogenesis of ES cells, and, for a given pathway, assign
      specific functions to each isoform. It appears now that a fine tuning of the
      MAPKs regulates both normal and pathological adipogenesis. The precise
      understanding of the cascade of these molecular events and the way to regulate
      them will be certainly crucial in order to efficiently fight obesity.

PMID- 15733738
TI  - Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and
      famine.
AB  - In this review, we propose that actions of the lipid-lowering, apoptosis
      inhibiting effects of certain "longevity genes" oppose the life-shortening
      consequences of lipotoxicity and lipoapoptosis. We note that lipotoxicity occurs
      whenever leptin action is deficient, or whenever satiety is overridden, as in
      forced or voluntary overfeeding ("supersizing"). The role of hyperleptinemia, we
      suggest, is to extend survival during famine by permitting the storage of surplus
      calories in adipocytes without concomitant injury to nonadipose tissues from
      ectopic lipid deposits. It achieves this lipid partitioning by (1) restraining
      the level of overnutrition so as not to exceed the available adipocyte storage
      space and (2) enhancing oxidation of any ectopic lipid overflow: The mechanisms
      of lipoapoptosis are discussed, and the possibility that metabolic syndrome is
      the human equivalent of rodent lipotoxicity is suggested.

PMID- 15733739
TI  - HIV antiretroviral treatment alters adipokine expression and insulin sensitivity
      of adipose tissue in vitro and in vivo.
AB  - HIV-1-infected patients on antiretroviral therapy frequently develop a
      lipodystrophy syndrome, characterized by peripheral lipoatrophy and visceral fat
      redistribution associated with metabolic alterations including dyslipidemia and
      insulin resistance. Its pathophysiology remains unclear but the antiretroviral
      treatment, associating protease inhibitors (PIs) and nucleoside analogue
      inhibitors of the viral reverse transcriptase (NRTIs), plays a major role. Some
      antiretroviral molecules inhibit differentiation and induce insulin resistance
      and apoptosis in adipose cells both in vitro and in vivo. In vitro, PIs and NRTIs
      increase the expression and secretion of pro-inflammatory cytokines such as TNF
      alpha, IL-6 and L-1beta, which are involved in altered adipocyte functions and
      decrease that of adiponectin, a positive modulator of insulin sensitivity.
      Similar alterations are observed in fat and serum from HIV-1-infected
      lipodystrophic patients under antiviral treatment associating PIs and NRTIs.
      Altered adipokine secretion could result from patients' exposure to PIs and NRTIs
      and lead to altered adipocyte differentiation, insulin resistance and apoptosis,
      ultimately resulting in lipoatrophy. These disorders probably result in a
      decreased secretion of adiponectin and an increased release of free fatty acids
      by insulin-resistant adipose tissue. Therefore, they could be involved in whole
      body insulin resistance and metabolic alterations in lipodystrophic HIV-1
      infected patients.

PMID- 15733740
TI  - Development of conjugated linoleic acid (CLA)-mediated lipoatrophic syndrome in
      the mouse.
AB  - Conjugated linoleic acids (CLA) are positional and geometric dienoic isomers of
      linoleic acid. Dietary CLA supplementation leads to a drop in fat mass in various
      species, including in humans. The t10,c12-CLA isomer is responsible for this anti
      obesity effect. The reduction of fat mass is especially dramatic in the mouse, in
      which it is associated with severe hyperinsulinemia, insulin resistance and
      massive liver steatosis. The origin of these adverse side effects and putative
      chronology of events leading to CLA-mediated lipoatrophic syndrome are presented
      and discussed in this review.

PMID- 15733741
TI  - Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory
      element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism
      and lipid synthesis in liver.
AB  - In mammals, the regulation of hepatic metabolism plays a key role in whole body
      energy balance, since the liver is the major site of carbohydrate metabolism
      (glycolysis and glycogen synthesis) and triglyceride synthesis (lipogenesis).
      Lipogenesis is regulated through the acute control of key enzyme activities by
      means of allosteric and covalent modifications. Moreover, the synthesis of most
      glycolytic and lipogenic enzymes is regulated in response to dietary status, in
      which glucose, in particular, is a crucial energy nutrient. This latter response
      occurs in large part through transcriptional regulation of genes encoding
      glycolytic and lipogenic enzymes. In the past few years, recent advances have
      been made in understanding the transcriptional regulation of hepatic glycolytic
      and lipogenic genes by insulin and glucose. Although insulin is a major regulator
      of hepatic lipogenesis, there is increasing evidence that glucose also
      contributes to the coordinated regulation of carbohydrate and lipid metabolism in
      liver. Here, we review the respective roles of the transcription factor sterol
      regulatory element binding protein-1c (SREBP-1c) in mediating the effect of
      insulin on hepatic gene expression, and the role of carbohydrate responsive
      element binding protein (ChREBP) in regulating gene transcription by glucose.

PMID- 15733742
TI  - AMP-activated protein kinase: balancing the scales.
AB  - AMP-activated protein kinase (AMPK) is the central component of a protein kinase
      cascade that plays a key role in the regulation of energy control. AMPK is
      activated in response to an increase in the ratio of AMP:ATP within the cell.
      Activation requires phosphorylation of threonine 172 within the catalytic subunit
      of AMPK by an upstream kinase. The identity of the upstream kinase in the cascade
      remained frustratingly elusive for many years, but was recently identified as
      LKB1, a kinase that is inactivated in a rare hereditary form of cancer called
      Peutz-Jeghers syndrome. Once activated, AMPK initiates a series of responses that
      are aimed at restoring the energy balance within the cell. ATP-consuming,
      anabolic pathways, such as fatty acid synthesis and protein synthesis are
      switched-off, whereas ATP-generating, catabolic pathways, such as fatty acid
      oxidation and glycolysis, are switched-on. More recent studies have indicated,
      that AMPK plays an important role in the regulation of whole body energy
      metabolism. The adipocyte-derived hormones, leptin and adiponectin, activate AMPK
      in peripheral tissues, including skeletal muscle and liver, increasing energy
      expenditure. In the hypothalamus, AMPK is inhibited by leptin and insulin,
      hormones which suppress feeding, whilst ghrelin, a hormone that increases food
      intake, activates AMPK. Furthermore, direct pharmacological activation of AMPK in
      the hypothalamus by 5-aminoimidazole-4-carboxamide ribose increases food intake
      in rats, demonstrating that AMPK plays a direct role in the regulation of
      feeding. Taken together these findings indicate that AMPK has a pivotal role in
      regulating pathways that control both energy expenditure and energy intake.

PMID- 15733743
TI  - Potential regulatory role of the farnesoid X receptor in the metabolic syndrome.
AB  - Dyslipidemia and gallbladder diseases are two current anomalies observed in
      patients suffering from the metabolic syndrome and type 2 diabetes. The bile acid
      activated nuclear receptor farnesoid X receptor (FXR) controls bile acid as well
      as lipid metabolism. Recent observations indicate a role for FXR also in
      carbohydrate metabolism. Hepatic FXR expression is altered in diabetic animal
      models in vivo and regulated by hormones and nutrients in vitro. At the molecular
      level, FXR activation modifies the transcriptional activity of different
      transcription factors controlling gluconeogenesis and lipogenesis, thus affecting
      in concert bile acid, lipid and carbohydrate metabolism. The present review
      focuses on recent advances in our understanding of the modulation of carbohydrate
      metabolism by FXR. These observations raise the intriguing possibility for a
      modulatory role of this receptor also in the metabolic syndrome.

PMID- 15733744
TI  - Positive and negative regulation of insulin signaling through IRS-1
      phosphorylation.
AB  - This review will provide insight on the current understanding of the regulation
      of insulin signaling in both physiological and pathological conditions through
      modulations that occur with regards to the functions of the insulin receptor
      substrate 1 (IRS1). While the phosphorylation of IRS1 on tyrosine residue is
      required for insulin-stimulated responses, the phosphorylation of IRS1 on serine
      residues has a dual role, either to enhance or to terminate the insulin effects.
      The activation of PKB in response to insulin propagates insulin signaling and
      promotes the phosphorylation of IRS1 on serine residue in turn generating a
      positive-feedback loop for insulin action. Insulin also activates several kinases
      and these kinases act to induce the phosphorylation of IRS1 on specific sites and
      inhibit its functions. This is part of the negative-feedback control mechanism
      induced by insulin that leads to termination of its action. Agents such as free
      fatty acids, cytokines, angiotensin II, endothelin-1, amino acids, cellular
      stress and hyperinsulinemia, which induce insulin resistance, lead to both
      activation of several serine/threonine kinases and phosphorylation of IRS1. These
      agents negatively regulate the IRS1 functions by phosphorylation but also via
      others molecular mechanisms (SOCS expression, IRS degradation, O-linked
      glycosylation) as summarized in this review. Understanding how these agents
      inhibit IRS1 functions as well as identification of kinases involved in these
      inhibitory effects may provide novel targets for development of strategies to
      prevent insulin resistance.

PMID- 15733745
TI  - Interaction of PTPB with the insulin receptor precursor during its biosynthesis
      in the endoplasmic reticulum.
AB  - PTP1B is a protein tyrosine-phosphatase predominantly located on the cystosolic
      surface of the endoplasmic reticulum. This tyrosine-phosphatase plays a major
      role in the regulation of the activity of the insulin receptor (IR). We have
      studied the interaction of the IR with PTP1B in living cells using
      bioluminescence resonance energy transfer (BRET). The IR was fused to Renilla
      luciferase and a substrate-trapping mutant of PTP1B was fused to the yellow
      variant of the green fluorescent protein (YFP). When the two partners interacted,
      an energy transfer occurred between the luciferase and the YFP, and a fluorescent
      signal, emitted by the YFP, could be detected. The interaction of the IR with
      PTP1B could be monitored in real time for more than 30 min. Insulin rapidly and
      dose-dependently stimulated this interaction. The basal (insulin-independent)
      interaction of IR with PTP1B was much lower with a soluble form than with the
      endoplasmic reticulum-targeted form of PTP1B, indicating that this basal
      interaction mainly occurred in the endoplasmic reticulum. In the basal state,
      PTP1B and the IR indeed co-localized in the endoplasmic reticulum, as
      demonstrated by confocal microscopy and cell fractionation experiments. Moreover,
      inhibition of IR processing with tunicamycin indicated that the basal interaction
      of PTP1B with IR occurred during biosynthesis of the IR precursor in the
      endoplasmic reticulum. These results strongly suggest that PTP1B not only
      dephosphorylates the insulin receptor that has been activated by insulin, but
      also regulates the insulin receptor precursor during its biosynthesis.
      Localisation of PTP1B to the endoplasmic reticulum may be important to prevent
      insulin-independent autonomous activity of the immature insulin receptor
      precursor.

PMID- 15733746
TI  - Transcriptomics applied to obesity and caloric restriction.
AB  - Caloric restriction still remains the most efficient way to promote weight loss.
      Deciphering the molecular basis of adaptation to energy restriction is critical
      for the tailoring of new therapeutic strategies. This review focuses on the
      recent input of gene profiling on adipose tissue in obesity pathogenesis and on
      the new insights on adaptations occurring during very low caloric diet (VLCD) in
      humans. Hypocaloric diets improve a wide range of metabolic parameters including
      lipolytic efficiency, insulin sensitivity, and inflammatory profile. In the
      subcutaneous white adipose tissue (scWAT) the VLCD induced a decrease in the mRNA
      levels for the antilipolytic alpha2-adrenergic receptor associated with changes
      in catecholamine-induced adipocyte lipolytic capacity. The improvement in insulin
      sensitivity was not associated with a change in subcutaneous adipose tissue
      adiponectin gene expression or in its plasma level, suggesting that adiponectin
      is not involved in the regulation of VLCD-induced improvement of insulin
      sensitivity and that there is a small contribution of subcutaneous adipose tissue
      to plasma adiponectin levels. Pangenomic microarray studies in human scWAT
      revealed that a panel of inflammatory markers and acute phase reactants were over
      expressed in obese compared to lean subjects. Caloric restriction improved the
      inflammatory profile of obese subjects through a decrease of pro-inflammatory
      factors and an increase of anti-inflammatory molecules. These genes were mostly
      expressed in the stroma vascular fraction of the adipose tissue. Specific cell
      type isolation and immunohistochemistry demonstrated that monocyte/macrophage
      lineage cells were responsible for the expression of both mRNA and protein
      inflammatory markers. The acute phase proteins serum amyloid A was highly
      expressed in mature adipocytes from obese subjects. Caloric restriction decreased
      both serum amyloid mRNA and circulating levels. Obesity now clearly appears as
      chronic low-grade inflammation state. Modulation of the inflammatory pathways may
      represent new therapeutic targets for the treatment of obesity-related
      complications.

PMID- 15733747
TI  - The human adipose tissue is a source of multipotent stem cells.
AB  - Multipotent stem cells constitute an unlimited source of differentiated cells
      that could be used in pharmacological studies and in medicine. Recently, several
      publications have reported that adipose tissue contains a population of cells
      able to differentiate into different cell types including adipocytes,
      osteoblasts, myoblasts, and chondroblasts. More recently, stem cells with a multi
      lineage potential at the single cell level have been isolated from human adipose
      tissue. These cells, called human Multipotent Adipose-Derived Stem (hMADS) cells,
      have been established in culture and interestingly, maintain their
      characteristics with long-term passaging. The adipocyte differentiation of hMADS
      cells has been thoroughly studied and differentiated cells exhibit the unique
      feature of human adipocytes. Finally, potential applications of stem cells
      isolated from adipose tissue in medicine will be discussed.

PMID- 15733748
TI  - LIPGENE: an EU project to tackle the metabolic syndrome.
AB  - LIPGENE is a new 5-year sixth framework EU project involving researchers from 14
      EU countries. It will contribute to a reduction in the economic and social burden
      of the metabolic syndrome through research that will optimise the health impacts
      of dietary fat change. LIPGENE aims to: account for variation in genotype
      response to fatty acid modification; enable greater availability of food products
      that can enhance human health; enhance consumer awareness, and motivate adoption
      of dietary approaches to disease prevention. A truly integrated programme,
      LIPGENE incorporates human nutrition, animal nutrition, plant biotechnology, and
      economic and social/consumer sciences. The human nutrition packages will utilise
      data from an existing prospective study (SUVIMAX) to identify genotype and
      dietary interactions as risk factors for the metabolic syndrome. A multi-centre
      intervention will examine the effects of dietary fat on various risk factors for
      the metabolic syndrome, while molecular investigations will be supported by
      mechanistic and functional studies. The British Nutrition Foundation, as
      dissemination partners for this EU programme, is initiating a wide-reaching
      programme to disseminate information about the project and its findings. Further
      details, including lists of upcoming project-related events, are available at
      www.lipgene.tcd.ie and www.nutrition.org.uk/lipgene.

PMID- 15733750
TI  - Images in Resuscitation: Henning Ruben and the self inflating bag.

PMID- 15733751
TI  - Resuscitation great: Czar Alexander I, Emperor of Russia (1777-1825).

PMID- 15733752
TI  - An alternative approach to advancing resuscitation science.
AB  - Stagnant survival rates in out-of-hospital cardiac arrest remain a great impetus
      for advancing resuscitation science. International resuscitation guidelines, with
      all their advantages for standardizing resuscitation therapeutic protocols, can
      be difficult to change. A formalized evidence-based process has been adopted by
      the International Liason Committee on Resuscitation (ILCOR) in formulating such
      guidelines. Currently, randomized clinical trials are considered optimal
      evidence, and very few major changes in the Guidelines for Cardiopulmonary
      Resuscitation and Emergency Cardiovascular Care are made without such. An
      alternative approach is to allow externally controlled clinical trials more
      weight in Guideline formulation and resuscitation protocol adoption. In Tucson,
      Arizona (USA), the Fire Department cardiac arrest database has revealed a number
      of resuscitation issues. These include a poor bystander CPR rate, a lack of
      response to initial defibrillation after prolonged ventricular fibrillation, and
      substantial time without chest compressions during the resuscitation effort. A
      local change in our previous resuscitation protocols had been instituted based
      upon this historical database information.

PMID- 15733753
TI  - The Department of Health National Defibrillator Programme: analysis of downloads
      from 250 deployments of public access defibrillators.
AB  - From April 2000 to November 2002, the Department of Health (England) placed 681
      automated external defibrillators (AEDs) in 110 public places for use by
      volunteer lay first responders. An audit has been undertaken of the first 250
      deployments, of which 182 were for confirmed cardiac arrest. Of these, 177 were
      witnessed whilst 5 occurred in situations that were remote or initially
      inaccessible to the responders. The response interval between collapse and the
      initiation of CPR or AED placement was estimated to be 3-5 min in most cases.
      Ventricular fibrillation or rapid ventricular tachycardia (one case) was the
      first recorded rhythm in 146 cases (82%). In all, 44 of the 177 witnessed cases
      are known to have survived to hospital discharge (25%). Complete downloads are
      available for 173 witnessed cases and of these 140 were shocked: first-shock
      success, defined as termination of the fibrillatory waveform for 5 s or more, was
      achieved in 132 of them. When data quality permitted, the downloads were analysed
      with special reference to the numbers of compressions given and also to
      interruptions in compression sequences for ventilations, for rhythm analysis by
      the AED, for clinical checks, and for unexplained operator delays. The average
      rate of compressions during sequences was 120 min(-1), but because of
      interruptions, the actual number administered over a full minute from the first
      CPR prompt was a median of only 38. The speed of response by the lay first
      responders in relation to AED use was similar to that reported for healthcare
      professionals.

PMID- 15733754
TI  - The ABC of resuscitation and the Dutch (re)treat.
AB  - In 1982 the Netherlands made a unilateral decision to change the established
      airway-breathing-circulation (ABC) training sequence to a different approach that
      stressed efficiency in diagnosis and treatment. This Dutch approach became known
      as the CAB (circulation-airway-breathing) sequence. Twenty years later, being
      confronted with the new international guidelines (published 2000) that still use
      the ABC approach, the Netherlands Resuscitation Council (NRR) questioned again
      the validity of our persistence in using the "Dutch variant" of resuscitation.
      This resulted in revised national guidelines that conform again with the
      international guidelines. This article restates the main rationale and arguments
      behind the original decision to change to a Dutch (CAB) version of resuscitation
      over 20 years ago. The national decision to adopt the ABC approach once again was
      mainly to prevent resuscitation in the Netherlands from being isolated from the
      rest of the world and was not based on present knowledge of physiology and
      resuscitation. The authors hope that this article will open the discussion once
      again.

PMID- 15733755
TI  - Post-shock chest compression delays with automated external defibrillator use.
AB  - PRIMARY OBJECTIVE: In a swine model of out-of-hospital ventricular fibrillation
      (VF) cardiac arrest, we established that automated external defibrillator (AED)
      defibrillation could worsen outcome from prolonged VF compared with manual
      defibrillation. Worse outcomes were due to substantial interruptions and delays
      in chest compressions for AED rhythm analyses and shock advice. In particular,
      the mean interval from first AED shock to first post-shock compressions was 46+/
      6s. We hypothesized that the delay from shock to provision of chest compressions
      is similar in the out-of-hospital setting. MATERIALS AND METHODS: We conducted a
      retrospective observational review of AED-treated adult VF cardiac arrest victims
      over a 26-month period to determine the interval from the first AED
      defibrillation attempt to the initial provision of post-shock chest compressions
      for out-of-hospital VF cardiac arrests. A two-tiered, single emergency medical
      service (EMS) system with AED-equipped first responders serves our area of 400
      km2 with a population of 487,000 people. The defibrillators record a detailed
      sequence of events during the resuscitation effort that includes the
      electrocardiogram with real clock times and a recording of surrounding audible
      actions. RESULTS: A median of 38 s (IQR 15, 61 s) elapsed between the first shock
      and the initiation of chest compressions. Approximately half of the delay was due
      to mechanical/electronic factors and the remainder due to human factors. Of 64
      adults in VF, 45 (70%) died before hospital admission, 19 (30%) survived to
      admission and 10 (16%) survived to hospital discharge. CONCLUSION: Substantial
      delays in the provision of post-shock chest compressions are typical in this EMS
      system with AED-equipped first responders.

PMID- 15733756
TI  - Time matters; what is the time in your defibrillator? An observational study in
      30 emergency medical service systems.
AB  - BACKGROUND: Measuring different intervals during cardiopulmonary resuscitation is
      a key element of resuscitation performance. For accurate time measurements, the
      internal clocks of automated external defibrillator (AEDs) need to be
      synchronized with the dispatch centre time. AIM: To determine the present
      practice of using and synchronizing the AED clocks in five regions in Finland.
      METHODS: During a single morning, the time of all AED clocks in the emergency
      medical service (EMS) systems of five large hospital districts were checked and
      compared with the dispatch centre time. A questionnaire about synchronisation
      policy and documentation of the first defibrillatory shock was also e-mailed to
      the local EMS medical supervisors. RESULTS: Eighty-eight AEDs were checked in 30
      EMS systems. The mean deviation from dispatch centre time was 412 (+/-1001) s.
      There was no difference between EMS systems with (N = 7) or without (N = 23)
      written guidelines regarding synchronisation. Many EMSs reported that they
      document the time of the first shock without synchronisation of clocks.
      CONCLUSIONS: Synchronisation of AED clocks is not widespread in Finland.
      Instructions to synchronize have been issued in a minority of EMS systems.
      Despite this, time deviations are large, and erroneous times are recorded.

PMID- 15733757
TI  - Better adherence to the guidelines during cardiopulmonary resuscitation through
      the provision of audio-prompts.
AB  - OBJECTIVE: Quality assurance to optimize clinical resuscitation performance is
      important. The aims of the present study were to identify the deficiencies in the
      clinical practice of resuscitation by motion analysis of video-recorded
      cardiopulmonary resuscitation (CPR), and to evaluate the effectiveness of quality
      improvement strategies based on audio-prompt methods. MATERIALS AND METHODS: A
      two-stage prospective trial was conducted. The first stage (observation group)
      was designed to identify any major clinical nonconformity to current
      resuscitation guidelines by videotaped CPR sessions. The second stage
      (intervention group) was designed to evaluate the effectiveness of audio prompts
      in ameliorating the problems identified at the first stage. The demographic data
      of patients and CPR variables between the two groups were analysed. RESULTS: A
      total of 30 resuscitation attempts were recorded during study period: 17 patients
      were in the observation group and 13 patients in the intervention group.
      Inadequate number of chest compressions per minute, lack of re-oxygenation during
      prolonged intubation attempts and unnecessary hands-off periods were identified
      as the three most important deficiencies in CPR practice. Compared to the
      observation group, the intervention group showed a significant improvement in the
      hands-off period per minute during CPR (12.7 +/- 5.3 s versus 16.9+/-7.9 s, P <
      0.05), the total hands-off time during CPR (164 +/- 94 s versus 273 +/- 153 s, P
      < 0.05), the proportion of intubation attempts taking under 20 s (56.3% versus
      10%, P < 0.05). CONCLUSIONS: Audio-prompts can improve the adherence to current
      CPR guidelines in the clinical setting significantly. The quality improvement
      measures described in this study are helpful in translating CPR knowledge into
      clinical practice.

PMID- 15733758
TI  - How to become an under 11 rescuer: a practical method to teach first aid to
      primary schoolchildren.
AB  - It has been calculated that, on average, 20% of the population should be trained
      to provide first aid, if a significant reduction of mortality is to be achieved.
      However, wide dissemination of the principles of emergency care poses a series of
      difficulties. As a partial solution, we have designed a first aid training course
      for children aged 8-11 years in their last three courses at primary school.
      According to the Italian school system, classes in primary school are indicated
      as I through V, from start to ending. The course addresses three issues: the
      broken tooth, nose bleeding and paediatric basic life support (PBLS). The course
      is divided into 17 didactic modules: each module contains a theoretical lecture,
      a practical demonstration by the trainer and a session for the trainees to
      practice under supervision. The aim of the study was to evaluate the benefit of
      teaching emergency procedures including practical sessions for pupils in primary
      schools. Four hundred and sixty-nine children were enrolled: the evaluation
      consisted of a 13 question multiple-choice written test taken at the end of the
      theoretical session and a semi-structured test at one month. Two hundred and
      seventy-one children attended to the theoretical lesson only, without going
      through the practical session (Group A), while the remaining 189 children
      completed the practical training (Group B). The outcome of the evaluation
      demonstrates that older children (in their V school class) score better than
      those in their IV and III class (p < 0.001). However, when comparing Group A and
      Group B in each class, the children that had also been exposed to the practical
      training (Group B) scored significantly better (V(B) versus V(A) p < 0.001; IV(B)
      versus IV(A) p < 0.001; III(B) versus III(A) p < 0.01). In conclusion, this
      proposed method of teaching emergency first aid could be successful in training
      primary school children. The permanent integration of the subject into the core
      curriculum of primary schools, and extended to higher school levels, could help
      in disseminating the culture of emergency care in the general population.

PMID- 15733759
TI  - Body surface mapping versus the standard 12 lead ECG in the detection of
      myocardial infarction amongst emergency department patients: a Bayesian approach.
AB  - OBJECTIVE: To determine if body surface mapping (BSM) is better than the standard
      12 lead ECG in the diagnosis of acute myocardial infarction amongst emergency
      department patients. SETTING: A University affiliated inner-city emergency
      department. PARTICIPANTS: People presenting to an emergency department with
      symptoms compatible with myocardial ischaemia/infarction. MAIN OUTCOME MEASURES:
      Myocardial infarction as defined by either standard 12 lead ECG changes with
      associated cardiac marker rise, Troponin T >0.1 microg/ml at > 12 h or
      autopsy/surgical findings of fresh macroscopic infarction. RESULTS: BSM had an
      overall sensitivity of 47.1% versus 40% for the 12 lead ECG (P < 0.001).
      Specificity for the BSM was 85.6% versus 93.7% for the 12 lead ECG (P < 0.001).
      These findings were consistent for low/moderate and high risk subgroups. Bayesian
      analysis demonstrates that indiscriminate use of BSM would result in a clinically
      important overdiagnosis of myocardial infarction amongst emergency department
      patients. CONCLUSIONS: BSM has a higher sensitivity, but a lower specificity for
      the diagnosis of myocardial infarction.

PMID- 15733760
TI  - Detection of a systolic pressure threshold for reliable readings in pulse
      oximetry.
AB  - OBJECTIVE: To determine the error of measurement in pulse oximetry with a
      decreased arterial perfusion and to identify a systolic pressure threshold for
      (1) initial detection and (2) a reliable reading of oxygen saturation. DESIGN: An
      experimental clinical prospective study. The study was approved by the local
      ethics committee. SETTING: Eighteen bed intensive care unit at a University
      hospital. PATIENTS AND PARTICIPANTS: Twenty-five adult mechanically ventilated
      and critically ill patients in the ICU during a 3-month period. INTERVENTIONS: A
      blood pressure cuff at the upper arm (same side as an arterial catheter already
      in place) was inflated to decrease the arterial pulsatile flow. The cuff was
      deflated stepwise and the resulting oxygen saturation was measured
      simultaneously. The error of measurement [delta S = SpO2 (baseline)-SpO2
      (indicated)] was calculated for each 5 mmHg of blood pressure (BP). MEASUREMENTS
      AND RESULTS: Twenty-five patients (9 female, 16 male, 48 +/- 15.9 years old) with
      a mean SpO2 of 98.3 +/- 1.5% and a BP of 129 +/- 18.4 mmHg participated. The mean
      systolic BP to obtain initial readings with pulse oximetry was 45.8 +/- 17.7
      (range, 25-101) mmHg (35% of the baseline pressure) resulting in lower readings
      of pulse oximetry (mean -11.5 +/- 13.6%, range -45 to +4%). With a systolic BP >
      80 mmHg the mean bias was within the manufacturers limits of +/-2%. CONCLUSIONS:
      Pulse oximetry is reliable with a systolic blood pressure > 80 mmHg. The lower
      the BP, the lower the pulse oximetry readings leading to a bias of up to -45%.

PMID- 15733761
TI  - Effects of decreasing inspiratory times during simulated bag-valve-mask
      ventilation.
AB  - During CPR, an inspiratory time of 2 s is recommended when the airway is
      unprotected; indicating that approximately 30% of the resuscitation attempt is
      spent on ventilation, but not on chest compressions. Since survival rates may not
      decrease when ventilation levels are relatively low, and uninterrupted chest
      compressions with a constant rate of approximately 100/min have been shown to be
      lifesaving, it may be beneficial to cut down the time spent on ventilation, and
      instead, increase the time for chest compressions. In an established bench model
      of a simulated unprotected airway, we evaluated if inspiratory time can be
      decreased from 2 to 1 s at different lower oesophageal sphincter pressure (LOSP)
      levels during ventilation with a bag-valve-mask device. In comparison with an
      inspiratory time of 2 s, 1 s resulted in significantly (p < 0.001) higher peak
      airway pressure and peak inspiratory flow rate, while lung tidal volumes at all
      LOSP levels were clinically comparable. Neither ventilation strategy produced
      stomach inflation at 20 cmH2O LOSP, and 1 s versus 2 s inspiratory time did not
      produce significantly higher (mean +/- S.D.) stomach inflation at 15 (8 +/-9 ml
      versus 0 +/- 0 ml; p < 0.01) and 10 cmH2O LOSP (69 +/- 20 ml versus 34 +/- 18 ml;
      p < 0.001), and significantly lower stomach inflation at 5 cmH2O LOSP (219 +/- 16
      ml versus 308 +/- 21 ml; p < 0.001) per breath. Total cumulative stomach
      inflation volume over constantly decreasing LOSP levels with an inspiratory time
      of 2 s versus 1 s was higher (6820 ml versus 5920 ml). In conclusion, in this
      model of a simulated unprotected airway, a reduction of inspiratory time from 2
      to 1 s resulted in a significant increase of peak airway pressure and peak
      inspiratory flow rate, while lung tidal volumes remained clinically comparable
      (up to approximately 15% difference), but statistically different due to the
      precise measurements. Theoretically, this may increase the time available for,
      and consequently the actual number of, chest compressions during CPR by
      approximately 25% without risking an excessive increase in stomach inflation.

PMID- 15733762
TI  - The value of portable ultrasound for evaluation of cardiomegaly patients
      presenting at the emergency department.
AB  - OBJECTIVES: The purpose of this study was to evaluate the value of a hand-carried
      portable ultrasound device in the emergency department for patients with
      cardiomegaly and evaluate its impact on diagnosis and treatment. We compared the
      results of the portable ultrasound with the results of physical examination and
      with standard echocardiograph (SE) in the cardiomegaly patients in emergency
      department. BACKGROUND: Recently, small portable ultrasound devices have been
      introduced, and they need more extensive study to evaluate their application.
      METHODS: We used the OptiGo (Agilent Technologies, Andover, MA) portable device
      to evaluate emergency patients, and compared it with two SE devices available for
      this study, the Hewlett Packard (Sono 5500; Andover, MA) or the Vingmed (System
      V; Horten, Norway). Each of 100 patients was studied by physical examination
      first then examined with the portable ultrasound and standard echocardiography.
      The yields from physical examination and portable echocardiography were compared
      and results of the standard and portable were also compared. RESULTS: There were
      a total of 243 cardiovascular findings detected by the standard echocardiographic
      examination in the 100 patients studied. Cardiac examination failed to detect 40%
      of the overall findings but the portable device missed only 17% of all findings.
      The portable device evaluated 201 conditions correctly (83%) and missed relevant
      clinical findings in 37 (17%) as compared to standard echocardiography, but in
      only 12 (5%) were these findings of major importance As an overall measure of
      diagnostic value, the portable device would have added to clinical judgment, thus
      boosting diagnostic accuracy from 62% to 83%. CONCLUSIONS: Portable ultrasound
      technology can provide rapid, readily available and important clinical
      information for emergency physicians in the management of emergency patients with
      cardiomegaly.

PMID- 15733763
TI  - Modeling instructor preferences for CPR and AED competence estimation.
AB  - INTRODUCTION: Cardiopulmonary resuscitation (CPR) and automated external
      defibrillator (AED) skills competency can be tested using a checklist of
      component skills, individually graded "pass" or "fail." Scores are typically
      calculated as the percentage of skills passed, but may differ from an
      instructor's overall subjective assessment of simulated CPR or AED adequacy.
      OBJECTIVE: To identify and evaluate composite measures (methods for scoring
      checklists) that reflect instructors' subjective assessments of CPR or AED skills
      performance best. METHODS: Associations between instructor assessment and lay
      volunteer skill performance were made using 6380 CPR and 3313 AED skill retention
      tests collected in the Public Access Defibrillation Trial. Checklists included
      CPR skills (e.g., calling 911, administering compressions) and AED skills (e.g.,
      positioning electrodes, shocking within 90 s of AED arrival). The instructor's
      subjective overall assessment (adequate/inadequate) of CPR performance
      (perfusion) or AED competence (effective shock) was compared to composite
      measures. We evaluated the traditional composite measure (assigning equal weights
      to individual skills) and several nontraditional composite measures (assigning
      variable weights). Skills performed out of sequence were further weighted from 0%
      (no credit) to 100% (full credit). RESULTS: Composite measures providing full
      credit for skills performed out of sequence and down-weighting process skills
      (e.g., calling 911, clearing oneself from the AED) had the strongest association
      with the instructor's subjective assessment; the traditional CPR composite
      measure had the weakest association. CONCLUSION: Our findings suggest that
      instructors in public CPR and AED classes may tend to down-weight process skills
      and to excuse step sequencing errors when evaluating CPR and AED skills
      subjectively for overall proficiency. Testing methods that relate classroom
      performance to actual performance in the field and to clinical outcomes require
      further research.

PMID- 15733764
TI  - The three-phase model of cardiac arrest as applied to ventricular fibrillation in
      a large, urban emergency medical services system.
AB  - BACKGROUND: Cardiac arrest is responsible for significant morbidity and
      mortality, with consistently poor outcomes despite the rapid availability of
      prehospital personnel for defibrillation attempts in patients with ventricular
      fibrillation (VF). Recent evidence suggests a period of cardiopulmonary
      resuscitation (CPR) prior to defibrillation attempts may improve outcomes in
      patients with moderate time since collapse (4-10 min). OBJECTIVES: To determine
      cardiac arrest outcomes in our community and explore the relationship between
      time since collapse, performance of bystander CPR, and survival. METHODS: Non
      traumatic cardiac arrest data were collected prospectively over an 18-month
      period. Patients were excluded for: age <18 years, a "Do Not Attempt
      Resuscitation" (DNAR) directive, determination of a non-cardiac etiology for
      arrest, and an initially recorded rhythm other than VF. Patients were stratified
      by time since collapse (<4, 4-10, > 10 min, and unknown) and compared with regard
      to survival and neurological outcome. In addition, patients with and without
      bystander CPR were compared with regard to survival. RESULTS: : A total of 1141
      adult non-traumatic cardiac arrest victims were identified over the 18-month
      study period. This included 272 patients with VF as the initially recorded
      rhythm. Of these, 185 had a suspected cardiac etiology for the arrest; survival
      to hospital discharge was 15% in this group, with 82% of these having a good
      outcome or only moderate disability. Survival was highest among patients with
      time since collapse of less than 4 min and decreased with increasing time since
      collapse. There were no survivors among patients with time since collapse greater
      than 10 min. Among patients with time since collapse of 4 min or longer, survival
      was significantly higher with the performance of bystander CPR; there was no
      survival advantage to bystander CPR among patients with time since collapse less
      than 4 min. CONCLUSIONS: The performance of bystander CPR prior to defibrillation
      by EMS personnel is associated with improved survival among patients with time
      since collapse longer than 4 min but not less than 4 min. These data are
      consistent with the three-phase model of cardiac arrest.

PMID- 15733765
TI  - Cold simple intravenous infusions preceding special endovascular cooling for
      faster induction of mild hypothermia after cardiac arrest--a feasibility study.
AB  - OBJECTIVE: Mild therapeutic hypothermia has shown to improve neurological outcome
      after cardiac arrest. Our study investigated the efficacy and safety of cold
      simple intravenous infusions for induction of hypothermia after cardiac arrest
      preceding further cooling and maintenance of hypothermia by specialised
      endovascular cooling. METHODS: All patients admitted after cardiac arrest of
      presumed cardiac aetiology were screened. Patients enrolled received 2000 ml of
      ice-cold (4 degrees C) fluids via peripheral venous catheters. As soon as
      possible endovascular cooling was applied even if the cold infusions were not
      completed. The target temperature was defined as 33 +/- 1 degrees C. All
      temperatures recorded were measured via bladder-temperature probes. The primary
      endpoint was the time from return of spontaneous circulation to reaching the
      target temperature. Secondary endpoints were changes in haemodynamic variables,
      oxygenation, haemoglobin, clotting variables and neurological outcome. RESULTS:
      Out of 167 screened patients 26 (15%) were included. With a total amount of 24 +/
      7 ml/kg cold fluid at 4 degrees C the temperature could be lowered from 35.6 +/-
      1.3 degrees C on admission to 33.8 +/- 1.1 degrees C. The target temperature was
      reached 185 +/- 119 min after return of spontaneous circulation, 135 +/- 112 min
      after start of infusion, and 83 +/- 85 min after start of endovascular cooling.
      Except for two patients showing radiographic signs of mild pulmonary edema no
      complications attributable to the infusions could be observed. Thirteen patients
      (50%) survived with favourable neurological outcome. CONCLUSION: Our results
      indicate that induction of mild hypothermia with infusion of cold fluids
      preceding endovascular cooling is safe and effective.

PMID- 15733766
TI  - Incomplete chest wall decompression: a clinical evaluation of CPR performance by
      EMS personnel and assessment of alternative manual chest compression
      decompression techniques.
AB  - BACKGROUND: Complete chest wall recoil improves hemodynamics during
      cardiopulmonary resuscitation (CPR) by generating relatively negative
      intrathoracic pressure and thus draws venous blood back to the heart, providing
      cardiac preload prior to the next chest compression phase. OBJECTIVE: Phase I was
      an observational case series to evaluate the quality of chest wall recoil during
      CPR performed by emergency medical services (EMS) personnel on patients with an
      out-of-hospital cardiac arrest. Phase II was designed to assess the quality of
      CPR delivered by EMS personnel using an electronic test manikin. The goal was to
      determine if a change in CPR technique or hand position would improve complete
      chest wall recoil, while maintaining adequate duty cycle, compression depth, and
      correct hand position placement. Standard manual CPR and three alternative manual
      CPR approaches were assessed. METHODS AND RESULTS: Phase I--The clinical
      observational study was performed by an independent observer noting incomplete
      chest wall decompression and correlating that observation with electronically
      measured airway pressures during CPR in adult patients with out-of-hospital
      cardiac arrest. Rescuers were observed to maintain some residual and continuous
      pressure on the chest wall during the decompression phase of CPR, preventing full
      chest wall recoil, at some time during resuscitative efforts in 6 (46%) of 13
      consecutive adults (average +/- S.D. age 63 +/-5.8 years). Airway pressures were
      consistently positive during the decompression phase (>0 mmHg) during those
      observations. Phase II: This randomized prospective trial was performed on an
      electronic test manikin. Thirty EMS providers (14 EMT-Basics, 5 EMT
      Intermediates, and 11 EMT-Paramedics), with an average age +/- S.D. of 32 +/- 8
      years and 6.5 +/- 4.2 years of EMS experience, performed 3 min of CPR on a
      Laerdal Skill Reporter CPR manikin using the Standard Hand Position followed by 3
      min of CPR (in random order) using three alternative CPR techniques: (1) Two
      Finger Fulcrum Technique--lifting the heel of the hand slightly but completely
      off the chest during the decompression phase of CPR using the thumb and little
      finger as a fulcrum; (2) Five-Finger Fulcrum Technique--lifting the heel of the
      hand slightly but completely off the chest during the decompression phase of CPR
      using all five fingers as a fulcrum; and (3) Hands-Off Technique--lifting the
      heel and all fingers of the hand slightly but completely off the chest during the
      decompression phase of CPR. These EMS personnel did not know the purpose of the
      studies prior to or during this investigation. Adequate compression depth was
      poor for all hand positions tested and ranged only from 29.9 to 48.5% of all
      compressions. When compared with the Standard Hand Position, the Hands-Off
      Technique decreased mean compression duty cycle from 46.9 +/- 6.4% to 33.3 +/-
      4.6%, (P < 0.0001) but achieved the highest rate of complete chest wall recoil
      (95.0% versus 16.3%, P < 0.0001) and was 129 times more likely to provide
      complete chest wall recoil (OR: 129.0; CI: 43.4-382.0). There were no significant
      differences in accuracy of hand placement, depth of compression, or reported
      increase in fatigue or discomfort with its use compared with the Standard Hand
      Position. CONCLUSIONS: Incomplete chest wall decompression was observed at some
      time during resuscitative efforts in 6 (46%) of 13 consecutive adult out-of
      hospital cardiac arrests. The Hands-Off Technique decreased compression duty
      cycle but was 129 times more likely to provide complete chest wall recoil (OR:
      129.0; CI: 43.4-382.0) compared to the Standard Hand Position without differences
      in accuracy of hand placement, depth of compression, or reported increase in
      fatigue or discomfort with its use. All forms of manual CPR tested (including the
      Standard Hand Position) in professional EMS rescuers using a recording manikin
      produced an inadequate depth of compression more than half the time. These data
      support development and testing of more effective means to deliver manual as well
      as mechanical CPR.

PMID- 15733767
TI  - Effects of incomplete chest wall decompression during cardiopulmonary
      resuscitation on coronary and cerebral perfusion pressures in a porcine model of
      cardiac arrest.
AB  - INTRODUCTION: Recent data suggest that generation of negative intrathoracic
      pressure during the decompression phase of CPR improves hemodynamics, organ
      perfusion and survival. HYPOTHESIS: Incomplete chest wall recoil during the
      decompression phase of standard CPR increases intrathoracic pressure and right
      atrial pressure, impedes venous return, decreases compression-induced aortic
      pressures and results in a decrease of mean arterial pressure, coronary and
      cerebral perfusion pressure. METHODS: Nine pigs in ventricular fibrillation (VF)
      for 6 min, were treated with an automated compression/decompression device with a
      compression rate of 100 min(-1), a depth of 25% of the anterior-posterior
      diameter, and a compression to ventilation ratio of 15:2 with 100% decompression
      (standard CPR) for 3 min. Compression was then reduced to 75% of complete
      decompression for 1 min of CPR and then restored for another 1 min of CPR to 100%
      full decompression. Coronary perfusion pressure (CPP) was calculated as the
      diastolic (aortic (Ao)-right atrial (RA) pressure). Cerebral perfusion pressure
      (CerPP) was calculated multiple ways: (1) the positive area (in mmHg s) between
      aortic pressure and intracranial pressure (ICP) waveforms, (2) the coincident
      difference in systolic and diastolic aortic and intracranial pressures (mmHg),
      and (3) CerPP = MAP--ICP. ANOVA was used for statistical analysis and all values
      were expressed as mean +/- S.E.M. The power of the study for an alpha level of
      significance set at 0.05 was >0.90. RESULTS: With CPR performed with 100%-75%
      100% of complete chest wall recoil, respectively, the CPP was 23.3 +/- 1.9, 15.1
      +/- 1.6, 16.6 +/- 1.9, p = 0.003; CerPP was: (1) area: 313.8 +/- 104, 89.2 +/-
      39, 170.5 +/- 42.9, p = 0.03, (2) systolic aortic minus intracranial pressure
      difference: 22.8 +/- 3.6, 16.5 +/- 4, 23.7 +/- 4.5, p = n.s., and diastolic
      pressure difference: 5.7 +/- 3, -2.4 +/- 2.4, 3.2 +/- 2.5, p = 0.04 and (3) mean:
      14.3 +/- 3, 7 +/- 2.9, 12.4 +/- 2.9, p = 0.03, diastolic aortic pressure was 28.1
      +/- 2.5, 20.7 +/- 1.9, 20.9 +/- 2.1, p = 0.0125; ICP during decompression was
      22.8 +/- 1.7, 23 +/- 1.5, 19.7 +/- 1.7, p = n.s. and mean ICP was 37.1 +/- 2.3,
      35.5 +/- 2.2, 35.2 +/- 2.4, p = n.s.; RA diastolic pressure 4.8 +/- 1.3, 5.6 +/-
      1.2, 4.3 +/- 1.2 p = 0.1; MAP was 52 +/- 2.9, 43.3 +/- 3, 48.3 +/- 2.9, p = 0.04;
      decompression endotracheal pressure, -0.7 +/- 0.1, -0.3 +/- 0.1, -0.75 +/- 0.1, p
      = 0.045. CONCLUSIONS: Incomplete chest wall recoil during the decompression phase
      of CPR increases endotracheal pressure, impedes venous return and decreases mean
      arterial pressure, and coronary and cerebral perfusion pressures.

PMID- 15733768
TI  - Myocardial ischaemic preconditioning in the pig has no effect on the ventricular
      fibrillation and defibrillation thresholds.
AB  - INTRODUCTION: The effects of myocardial ischaemia preconditioning in pigs on the
      vulnerability to ventricular fibrillation during subsequent ischaemic events are
      controversial. This study examined the time course of changes in ventricular
      fibrillation (VFT) and defibrillation (DFT) thresholds during transient
      myocardial ischaemia after a 45 min preconditioning period. METHODS AND RESULTS:
      In five open-chest pigs, VFT was measured after 3 min of regional myocardial
      ischaemia, at time 0, 2, 15, 30, 60 and 90 min (Control group). In seven other
      pigs (Test group), VFT was measured before (time 0) and 2, 15, 30, 60 and 90 min
      after ischaemic preconditioning by three consecutive 5 min periods of regional
      coronary occlusion, followed by 10 min of reperfusion. DFT was measured by
      increasing the stored energy systematically until successful defibrillation.
      Ischaemic preconditioning caused no significant change in the effective
      refractory period (ERP), VFT or DFT over the 90 min of the experiments. In the
      Control group, ERP remained stable for 30 min, though was significantly lower at
      90 min (178 +/- 28 ms) than at baseline (204 +/- 32 ms, P = 0.007). VFT and DFT
      remained unchanged throughout the experiments, and no difference was observed in
      ERP, VFT and DFT between the two groups at any time during the experiment.
      CONCLUSION: No changes were observed in the refractory duration, ventricular
      vulnerability or defibrillation energy requirements up to 90 min after
      ventricular ischaemic preconditioning in the pig.

PMID- 15733769
TI  - N-Acetylcysteine administered as part of the immediate post-traumatic
      resuscitation regimen does not significantly influence initiation of inflammatory
      responses or subsequent endotoxin hyporesponsiveness.
AB  - Polytrauma and resuscitative efforts induce extensive alterations in the host's
      internal environment and cellular responses that may be a serious threat to these
      patients. Administration of exogenous thiols has been recommended to modulate the
      post-traumatic inflammatory responses. In this study, we have investigated the
      effect of N-acetylcysteine (NAC) on the early markers of leukocyte activation and
      subsequent endotoxin hyporesponsiveness. Twenty-eight pigs were exposed to a
      standardized gunshot injury. First aid treatment and initial life saving surgery
      was started without delay. One group (n = 14) was randomised to receive NAC 200
      mg kg(-1) over 20 min, the remaining group was given the same volume of vehicle.
      Blood samples drawn at time points 0 and 75 min were also studied in vitro and
      stimulated with LPS or LPS plus NAC. Selected physiologic variables and degree of
      organ injury were equal in both groups. TNF-alpha, IL-1beta, and reactive oxygen
      species (ROS) tended to be lower in the NAC-group (NS). In vitro, NAC
      significantly reduced the release of the same cytokines after the LPS challenge
      in blood drawn before injury. NAC did not influence post-traumatic endotoxin
      tolerance. Adding NAC to the immediate resuscitation fluid did not influence the
      early post-traumatic organ injury, and initiation of inflammatory responses
      significantly, or endotoxin tolerance. In vitro, NAC significantly reduced
      proinflammatory cytokine release, but only in normal blood. The clinical value of
      this treatment regimen is probably restricted, both due to the unfavourable post
      traumatic internal environment and imposed dosing limitations.

PMID- 15733770
TI  - Neuroprotection with delayed initiation of prolonged hypothermia after in vitro
      transient global brain ischemia.
AB  - Prolonged therapeutic hypothermia (32-34 degrees C for 12-24 h) improves the
      functional outcome of comatose cardiac arrest survivors. It is generally believed
      that rapidly achieving target temperature optimizes neuroprotection. However,
      this hypothesis has not been tested systematically. In this study, we compared
      the neuroprotective effect of prolonged hypothermia initiated between 0 and 8 h
      after reoxygenation using an in vitro model of simulated global brain ischemia.
      Organotypic hippocampal slices were prepared from 5-day-old Wistar rat pups and
      cultured for 1 week prior to analysis. Ischemia was simulated by normothermic
      oxygen-glucose deprivation (OGD). Hypothermia (33 degrees C) was initiated 0-8 h
      after reoxygenation and maintained until 24 h post-injury. CA1 regional cell
      death was quantified by propidium iodide (PI) fluorescence. Release of 14-3-3
      beta protein was evaluated as a potential surrogate maker for neuroprotection.
      Hypothermia initiated 0, 1, 2, or 4 h after 30 min OGD reduced 24 h CA1 regional
      PI fluorescence by 47 +/- 34%, 85 +/- 4%, 88 +/- 3%, and 88 +/- 5% (P < 0.05 for
      all versus normothermic reoxygenation). Direct comparison of hypothermia
      initiated 4 or 8 h after reoxygenation revealed equivalent neuroprotection
      following 15 and 30 min OGD, but neither was protective after 60 min OGD.
      Hypothermia initiated 4 or 8 h after 30 min OGD reduced 14-3-3 beta release by 73
      +/- 11% and 92 +/- 4%, respectively (P < 0.01 for both versus normothermic
      reoxygenation). In this model, the neuroprotective effect of prolonged post
      ischemic hypothermia is both optimal and equivalent when initiated between 1 and
      8 h after reoxygenation. These results suggest the need for further in vivo
      studies to define the therapeutic window within which prolonged hypothermia is
      optimally neuroprotective after cardiac arrest.

PMID- 15733771
TI  - Feasibility of using a Single Uniform Simulated Megacode Scenario (SUSMS) during
      assessment in the Paediatric Advanced Life Support (PALS) course.

PMID- 15733772
TI  - Thrombolysis during cardiopulmonary resuscitation: a pilot randomised trial of
      thrombolysis in cardiac arrest (the TICA trial).

PMID- 15733773
TI  - Allometric cascade model and metabolic rate.

PMID- 15733775
TI  - Motor control of the costal and crural diaphragm--insights from transcranial
      magnetic stimulation in man.
AB  - The costal and crural parts of the diaphragm differ in their embryological
      development and physiological function. It is not known if this is reflected in
      differences in their motor cortical representation. We compared the response of
      the costal and crural diaphragms using varying intensities of transcranial
      magnetic stimulation of the motor cortex at rest and during submaximal and
      maximal inspiratory efforts. The costal and crural motor evoked potential
      recruitment curves during submaximal inspiratory efforts were similar. The
      response to stimulation before, during and at 10 and 30 min after 44 consecutive
      maximal inspiratory efforts was also the same. Using paired stimulations to
      investigate intra-cortical facilitatory and inhibitory circuits we found no
      difference between the costal and crural response with varying interstimulus
      intervals, or when conditioning and test stimulus intensity were varied. We
      conclude that supraspinal control of the costal and crural diaphragm is identical
      during inspiratory tasks.

PMID- 15733776
TI  - Significance of extracellular potassium in central respiratory control studied in
      the isolated brainstem-spinal cord preparation of the neonatal rat.
AB  - The significance of extracellular potassium in central respiratory control was
      investigated using the isolated brainstem-spinal cord preparation of the neonatal
      rat. Depth profiles of extracellular potassium activity ([K+])ECF in the medulla
      were measured with ion-sensitive microelectrodes. Although [K+]ECF increased with
      depth in medullary tissue during control (4 mM) and low (1 mM) potassium
      concentration ([K+])CSF superfusion, this gradient disappeared with higher
      [K+]CSF. With low [K+]CSF (1 mM), respiratory CO2 responsiveness was abolished,
      and increased with high [K+]CSF (8 mM). Respiratory frequency (fR) was diminished
      at low [K+]CSF (1 mM), and increased with elevated [K+]CSF (8 and 16 mM); with
      yet higher [K+]CSF (32 mM) apnea occurred after a transient increase in fR.
      Perforated patch recording revealed that high [K+]ECF decreased membrane
      resistance, depolarized membrane potential, and increased firing frequency in
      most of the recorded medullary neurons. High [K+]ECF also increased excitatory
      and inhibitory post-synaptic potentials of medullary neurons and augmented the
      functional connectivity among neurons. It is concluded that [K+]ECF is of
      importance in the maintenance of respiratory rhythm and central chemosensitivity.

PMID- 15733778
TI  - Exaggerated respiratory chemosensitivity and association with SaO2 level at 3568
      m in obesity.
AB  - To investigate whether obesity is associated with alterations in respiratory
      chemosensitivity, we compared the ventilatory response to hypoxia (HVR) and
      hypercapnia (HCVR) in 9 obese men (BMI: 37.0+/-4.3 kg m(-2)) and 10 lean men
      (BMI: 25.8+/-4.8 kg m(-2)). HVR (DeltaVE, L min(-1) per DeltaSaO2, %) was
      measured by a progressive isocapnic hypoxia technique, and HCVR
      (DeltaVE/DeltaPETCO2, L min(-1)Torr(-1)) was measured by a progressive
      hypercapnic method. HCVR, was greater (p<0.001) in the obese men (2.68+/-0.78)
      than in the lean men (1.4+/-0.45) as was HVR (p<0.05) (1.26+/-0.65 versus 0.71+/
      0.43, respectively). The difference (DeltaSaO2, 4.30+/-3.69 and 10.54+/-3.45 in
      the lean and obese men, respectively, p<0.01) between daytime (86+/-1 and 86+/
      1%) and nighttime SaO2 (81+/-3 and 76+/-4%) at a simulated altitude of 3658 m was
      significantly (p<0.05) correlated with both HVR (r=0.51) and HCVR (r=0.48). These
      results suggest that chemosensitivity in mildly obese men is increased, not
      blunted. Furthermore, otherwise healthy, obese individuals have the potential for
      significant desaturation during sleep at high altitude possibly due to
      exaggerated sleep-disordered breathing.

PMID- 15733777
TI  - Hypercapnic and hypoxic responses require intact neural transmission from the pre
      Botzinger complex.
AB  - The central respiratory network that includes the pre-Botzinger complex (pre
      BotC), a region believed to contain rhythmogenic neurons, is capable of
      responding to fluctuations in CO2 and pH. However, the role of inputs from this
      site in mediating ventilatory responses to hypercapnia and/or hypoxia in
      nonsedated animals is not well established. Therefore, in the present study we
      tested the hypothesis that altered transmission from the pre-BotC to its target
      sites would decrease chemosensory responsiveness to acute hypercapnia and
      modulate the ventilatory response to hypoxia. Colchicine was used to block axonal
      transport. At 48 h after bilateral microinjections of colchicine into the pre
      BotC (100 microg/uL, 100 nL/site), but not saline, the baseline frequency of
      breathing decreased; however, rhythmicity was not altered. In addition, there was
      a significant fall in the ventilatory response to hypercapnia (5 and 12% CO2) and
      hypoxia (8% O2). These findings indicate that, inputs from pre-BotC neurons are
      of critical importance in providing the normal ventilatory response to both
      hypercapnia and hypoxia.

PMID- 15733779
TI  - Changes in ventilatory responses to hypercapnia and hypoxia after intermittent
      hypoxia in humans.
AB  - The purpose of this study was to clarify the changes in hypercapnic and hypoxic
      ventilatory responses (HCVR and HVR) after intermittent hypoxia and following the
      cessation of hypoxic exposure. Twenty-nine males were assigned to one of four
      groups, i.e., a hypoxic (EX1-H, n=7) or a control (EX1-C, n=7) group in
      Experiment 1, and a hypoxic (EX2-H, n=8) or a control (EX2-C, n=7) group in
      Experiment 2. In each experiment, the hypoxic tent system was utilized for
      intermittent hypoxia, and the oxygen levels in the tent were maintained at 12.3+/
      0.2%. In Experiment 1, the EX1-H group spent 3 h/day in the hypoxic tent for 1
      week. HCVR and HVR were determined before and after 1 week of intermittent
      hypoxia, and again 1 and 2 week after the cessation of hypoxic exposure. In
      Experiment 2, the subjects in the EX2-H group performed 3 h/day for 2 weeks in
      intermittent hypoxia. HCVR and HVR tests were carried out before and after
      intermittent hypoxia, and were repeated again after 2 weeks of the cessation of
      hypoxic exposure. The slope of the HCVR in the EX1-H group did not show a
      significant increase after 1 week of intermittent hypoxia, while HCVR in the EX2
      H group increased significantly after 2 weeks of intermittent hypoxia. The HCVR
      intercept was unchanged following 1 or 2 weeks of intermittent hypoxia. There was
      a significant increase in the slope of the HVR after 1 and 2 weeks of
      intermittent hypoxia. The increased HCVR and HVR returned to pre-hypoxic levels
      after 2 weeks of the cessation of hypoxia. These results suggest that 3 h/day for
      2 weeks of intermittent hypoxia leads to an increase in central hypercapnic
      ventilatory chemosensitivity, which is not accompanied by a re-setting of the
      central chemoreceptors, and that the increased hypercapnic and hypoxic
      chemosensitivities are restored within 2 weeks after the cessation of hypoxia.

PMID- 15733780
TI  - Effect of increased diaphragm activation on diaphragm power spectrum center
      frequency.
AB  - Increased transdiaphragmatic pressure, reduced muscle blood flow, and increased
      duty cycle have all been associated with a reduction in the center frequency
      (CFdi) of the diaphragm's electrical activity (EAdi). However, the specific
      influence of diaphragm activation on CFdi is unknown. We evaluated whether
      increased diaphragm activation would result in a greater decline in the CFdi when
      pressure-time product (PTPdi) was kept constant. Five healthy subjects performed
      periods of intermittent quasi-static diaphragmatic contractions with a fixed duty
      cycle. In separate runs, subjects targeted transdiaphragmatic pressures (Pdi) by
      performing end-inspiratory holds with the glottis open and expulsive maneuvers at
      end-expiratory lung volume (EELV). Diaphragm activation and pressures were
      measured with an electrode array and balloons mounted on an esophago-gastric
      catheter, respectively. The EAdi, which was 25+/-8%(S.D.) of maximum at EELV,
      increased to 61+/-8% (P<0.001) when an identical Pdi (averaging 31+/-13 cmH2O)
      was generated at a higher lung volume (77% of inspiratory capacity). The latter
      was associated with a 17% greater decline in CFdi (P=0.012). In order to
      reproduce at EELV, the decrease in CFdi observed at the increased lung volume, a
      two-fold increase in PTPdi was required. We conclude that CFdi responds
      specifically to increased diaphragm activation when pressure-time product remains
      constant.

PMID- 15733781
TI  - Comparison of two methods to assess blood CO2 equilibration curve in mechanically
      ventilated patients.
AB  - In order to compare two mathematical methods to assess the blood CO2
      equilibration curve from a single blood gas analysis [Loeppky, J.A., Luft, U.C.,
      Fletcher, E.R., 1983. Quantitative description of whole blood CO2 dissociation
      curve and Haldane effect. Resp. Physiol. 51, 167-181; Giovannini, I., Chiarla,
      C., Boldrini, G., Castagneto, M., 1993. Calculation of venoarterial CO2
      concentration difference. J. Appl. Physiol. 74, 959-964], arterial and central
      venous blood gas analyses and oximetry were performed before and after
      ventilatory resetting, at constant arterial O2 saturation, in 12 mechanically
      ventilated patients. CO2 equilibration curves obtained from basal arterial blood
      gas analyses were used to predict arterial CO2 content after ventilatory
      resetting and vice versa. Internal consistency was very good for both methods and
      comparable. Method 2 also yielded excellent predictions of changes of arterial pH
      associated with ventilatory resetting. In determining Haldane effect, method 2
      yielded very stable results within the expected range of values, while method 1
      yielded a wider spread of results. Method 2 appeared more suitable to determine
      the Haldane effect in the conditions of the study, probably due to an approach
      minimizing the effect of potential sources of inaccuracy.

PMID- 15733782
TI  - Training to yoga respiration selectively increases respiratory sensation in
      healthy man.
AB  - Because yoga practitioners think they are benefiting from their breath training
      we hypothesized that yoga respiration training (YRT) could modify the respiratory
      sensation. Yoga respiration (YR) ("ujjai") consisted of very slow, deep breaths
      (2-3 min(-1)) with sustained breath-hold after each inspiration and expiration.
      At inclusion in the study and after a 2-month YRT program, we determined in
      healthy subjects their eupneic ventilatory pattern and their capacity to
      discriminate external inspiratory resistive loads (respiratory sensation),
      digital tactile mechanical pressures (somesthetic sensation) and sound-pressure
      stimulations (auditory sensation). Data were compared to a gender-, age-, and
      weight-matched control group of healthy subjects who did not undergo the YRT
      program but were explored at the same epochs. After the 2-month YRT program, the
      respiratory sensation increased. Thus, both the exponent of the Steven's power
      law (Psi=kPhin) and the slope of the linear-linear plot between Psi and mouth
      pressure (Pm) were significantly higher, and the intercept with ordinate axis of
      the Psi versus Pm relationship was lower. After YRT, the peak Pm developed
      against inspiratory loads was significantly lower, reducing the load-induced
      activation of respiratory afferents. YRT induced long-lasting modifications of
      the ventilatory pattern with a significant lengthening of expiratory duration and
      a modest tidal volume increase. No significant changes in somesthetic and
      auditory sensations were noted. In the control group, the respiratory sensation
      was not modified during a 15-min period of yoga respiration, despite the peak Pm
      changes in response to added loads were then significantly reduced. These data
      suggest that training to yoga respiration selectively increases the respiratory
      sensation, perhaps through its persistent conditioning of the breathing pattern.

PMID- 15733783
TI  - Oxygen consumption of the chicken embryo: interaction between temperature and
      oxygenation.
AB  - We measured the effects of hypoxia and changes in ambient temperature (T) on the
      oxygen consumption (VO2) of chicken embryos at embryonic days 11, 16 and 20 (E11,
      E16 and E20, respectively), and post-hatching day 1 (H1). Between 30 and 39
      degrees C, at E11 and E16, VO2 changed linearly with T, as in ectothermic
      animals, with a Q10 of about 2.1. At E20, VO2 did not significantly change with
      T, indicating the onset of endothermy. At H1, a drop in T increased VO2, a clear
      thermogenic response. Hypoxia (11% O2 for 30 min) decreased VO2, by an amount
      that varied with T and age. At H1, hypoxia lowered VO2 especially at low T. At
      E20, hypoxic hypometabolism was similar at all T. At E11 and E16, hypoxia lowered
      VO2 only at the higher T. In fact, at E11, with T=39 degrees C even a modest
      hypoxia (15-18% O2) decreased VO2. Upon return to normoxia after 40 min of 11%
      O2, VO2 did not rise above the pre-hypoxic level, indicating that the
      hypometabolism during hypoxia did not generate an O2 debt. At E11, during modest
      hypoxia (16% O2) at 36 degrees C, the drop in VO2 was lifted by raising the T to
      39 degrees C, suggesting that the hypoxic hypometabolism at 36 degrees C was not
      due to O2-supply limitation. In conclusion, the hypometabolic effects of hypoxia
      on the chicken embryo's VO2 depend on the development of the thermogenic ability,
      occurring predominantly at high T during the early (ectothermic phase) and at low
      T during the late (endothermic) phase. At E11, both low T and low oxygen force
      VO2 to drop. However, at a near-normal T, modest hypoxia promotes a hypometabolic
      response with the characteristics of regulated O2 conformism.

PMID- 15733784
TI  - Imaging iron stores in the brain using magnetic resonance imaging.
AB  - For the last century, there has been great physiological interest in brain iron
      and its role in brain function and disease. It is well known that iron
      accumulates in the brain for people with Huntington's disease, Parkinson's
      disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral
      infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down
      syndrome, AIDS and in the eye for people with macular degeneration. Measuring the
      amount of nonheme iron in the body may well lead to not only a better
      understanding of the disease progression but an ability to predict outcome. As
      there are many forms of iron in the brain, separating them and quantifying each
      type have been a major challenge. In this review, we present our understanding of
      attempts to measure brain iron and the potential of doing so with magnetic
      resonance imaging. Specifically, we examine the response of the magnetic
      resonance visible iron in tissue that produces signal changes in both magnitude
      and phase images. These images seem to correlate with brain iron content, perhaps
      ferritin specifically, but still have not been successfully exploited to
      accurately and precisely quantify brain iron. For future quantitative studies of
      iron content we propose four methods: correlating R2' and phase to iron content;
      applying a special filter to the phase to obtain a susceptibility map; using
      complex analysis to extract the product of susceptibility and volume content of
      the susceptibility source; and using early and late echo information to
      separately predict susceptibility and volume content.

PMID- 15733785
TI  - Visualization of the internal carotid artery using MRA images.
AB  - A virtual angioscopy system is implemented to visualize the inside of the
      internal carotid artery (ICA) for qualitative assessment of carotid artery
      stenosis using magnetic resonance angiography (MRA) images. The carotid artery is
      one of the body regions not accessible by real optical endoscopy but can be
      visualized with virtual endoscopy. In order to visualize the carotid artery, it
      is segmented using the region-growing algorithm after locating the initial seed
      on the presegmented binary image. The ICA is separated from the external carotid
      artery (ECA) using a priori knowledge of the anatomic structure after
      bifurcation. A fly-through path is computed based on the medial axis transform
      (MAT) to automatically move the virtual camera from the common carotid artery
      (CCA) to the ICA. Considering interactive rendering speed and usability of
      standard graphic hardware, the surface-rendering algorithm with the perspective
      projection method is used to generate an endoscopic view of the ICA. In addition,
      the endoscopic view with the raycasting algorithm is provided for off-line
      navigation of the carotid artery. Virtual angioscopy is highly recommended as a
      diagnostic tool for identifying the specific location of the stenosis and for
      analyzing the stenosis qualitatively. The virtual angioscopy system for carotid
      artery will benefit radiological diagnostics, medical education, surgical
      planning and postoperative assessment.

PMID- 15733786
TI  - Diffusion-weighted EPI with magnetization transfer contrast.
AB  - Capabilities of diffusion-weighted (DW) and magnetization transfer (MT) imaging
      are well established for tissue characterization in various pathologies
      individually. However, the effect of suppression of macromolecules on applying MT
      pulse on signals associated with DW imaging and resulting change in the apparent
      diffusion coefficient (ADC) of water molecules has not been demonstrated
      previously. In the present study, we have performed DW echo planar imaging (EPI)
      with and without MT preparation pulse to see the effect of macromolecular signal
      suppression on ADC. A total of 10 normal volunteers and 20 patients with
      different intracranial cystic lesions [abscesses (n=10), cystic tumors (n=5),
      arachnoid cysts (n=5)] were subjected to DW imaging (b=0 and 1000 s/mm(2)) with
      and without MT saturation pulse. Analysis of region of interest (ROI) from
      different areas of white matter in normal volunteers and in the wall and cavity
      of cystic lesions in patients was carried out for calculating the ADC values. We
      found a significant increase (P<.05) in the ADC values in brain parenchyma and
      cavity of those intracranial cystic lesions having considerable amount of
      proteins after the application of MT preparation pulse except for arachnoid
      cysts. This is due to the size of the macromolecules present in the normal and
      abnormal tissue. Our studies suggest that this technique is likely to give a
      novel image contrast and may be of value in improving the tissue specificity in
      pathologies associated with variable macromolecular size.

PMID- 15733787
TI  - Separation of physiological very low frequency fluctuation from aliasing by
      switched sampling interval fMRI scans.
AB  - Anesthetized children have dominant blood-oxygen-level-dependent (BOLD) signal
      sources presenting high-power fluctuations at very low frequencies (VLF <0.05
      Hz). Aliasing of frequencies higher than critically sampled has been regarded as
      one probable origin of the VLF fluctuations. Aliased signal frequencies change
      when the sampling rate of the data is altered. In this study, the aliasing of VLF
      BOLD signal fluctuation was analysed by switching the repetition time (TR) of
      magnetic resonance (MR) images. Eleven anesthetized children were imaged at 1.5 T
      using TRs of 500 and 1200 ms. The BOLD signal sources were separated with
      independent component analysis (ICA). Occipital cortex signal sources had
      nonaliased VLF fluctuation ( approximately 0.03 Hz) in 9 of 11 subjects. Arterial
      signal sources failed to present stable power peaks at frequencies lower than
      0.42 Hz presumably due to aliasing. Cerebrospinal fluid (CSF)-related signal
      sources showed nonaliased VLF in four subjects. In conclusion, the VLF BOLD
      signal fluctuation in the occipital cortex is a true physiological fluctuation,
      not a result of signal aliasing.

PMID- 15733788
TI  - Effects of coil dimensions and field polarization on RF heating inside a head
      phantom.
AB  - Deterioration of radiofrequency (RF) inhomogeneity with increasing static
      magnetic field in magnetic resonance imaging (MRI) is one of the fundamental
      challenges preventing their clinical rendition and posing safety hazards.
      Variation in RF coil designs could help redistribute RF energy absorption over
      the imaged object. This work is intended to determine experimentally the
      difference in RF heating produced within a human head phantom by in situ
      measurement of RF inhomogeneity as a function of coil design utilized at 8 T. The
      heating patterns of 1/4 wavelength (long) and 1/8 wavelength 11-cm (short)
      transverse electromagnetic (TEM) coils loaded with a homogeneous human head
      phantom at 340 MHz were evaluated. In addition, different transmit/receive (T/R)
      configurations were used in search for the possibility of "hot-spot" formation.
      Fluoroptic thermometry was used to measure temperatures in multiple positions in
      a head phantom made of ground turkey breast for RF powers corresponding to a
      specific absorption rate (SAR) of 4.0 W/kg for 10 min. Numerical simulations were
      performed to study the general RF power deposition patterns in phantoms at 340
      MHz including the effects of field polarization. The temperature increases varied
      from 0 to 0.8 degrees C for the long RF coil, while the short RF coil produced a
      maximum temperature change of 0.5 degrees C. Similar to ultra high-field
      electromagnetic simulations, these measurements revealed low peripheral and high
      deep-tissue heating at 8 T. The findings indicated that the largest temperature
      changes for both cases were less than 1 degrees C. While these results showed an
      increase in localized heating due to RF pulses at 8 T, they highlight that RF
      inhomogeneity could be redistributed using different RF coil designs through
      which the hot spots could be made cooler.

PMID- 15733789
TI  - MR imaging of caveolin gene-specific alterations in right ventricular wall
      thickness.
AB  - Caveolin-1 and caveolin-3 are expressed in the mammalian heart. Mice deficient in
      caveolin 1 or 3 exhibit cardiac abnormalities including left ventricular
      hypertrophy and reduced fractional shortening. Cardiac imaging technologies such
      as transthoracic echocardiography and cardiac-gated magnetic resonance imaging
      (MRI) are effective tools for the study of left ventricular morphology and
      function in mice; however, there has not been widespread use of these
      technologies in studies of right ventricular morphology. In particular, right
      ventricular wall thickness has been difficult to assess using cardiac imaging
      technologies. We report here the use of centerline analysis of cardiac-gated MR
      images to more accurately determine right ventricular wall thickness in the mouse
      heart. Right ventricular wall thickness was evaluated in Cav-1 null, Cav-3 null
      and Cav-1/3 null mice, as well as wild-type control mice. Using this technique,
      we find that caveolin null mice exhibit significant thickening of the right
      ventricular wall as compared with age-matched wild-type controls. Interestingly,
      right ventricular wall thickening is greatest in the Cav-1/3 null mice.
      Furthermore, significant right ventricular wall thickening is also seen in the
      Cav-1 null mice. Histological analyses revealed right ventricular hypertrophy
      consistent with the imaging results. These studies demonstrate the utility of MRI
      in determining right ventricular wall thickness and underscore the severity of
      the right ventricular hypertrophy in caveolin null mice.

PMID- 15733790
TI  - Determination of relaxation characteristics during preacute stage of
      lysophosphatidyl choline-induced demyelinating lesion in rat brain: an animal
      model of multiple sclerosis.
AB  - Relaxation time measurements were carried out during the preacute stage of lesion
      progression in an animal model of demyelination created in the internal capsule
      (ic) area of the rat brain using lysophosphatidyl choline (LPC). T1 and T2 were
      determined both before and after 36 h of lesion creation. Histology carried out
      on the rats after MR measurements showed focal demyelinating lesion and
      surrounding edema with prominent infiltration of inflammatory cells. Both T1 and
      T2 were statistically higher for the lesion compared to that determined before
      lesion creation. Percentage increase in T2 was found to be higher by
      approximately 45% compared to before lesion creation while T1 showed about 25%
      increase. Increase in T1 and T2 may be attributed to the early acute inflammatory
      response due to LPC. The beginning of the inflammatory response following LPC
      injection may also be a contributing factor. The study demonstrates that the
      quantitative estimate of MR relaxation provides useful information on the
      pathological events occurring during the early phase of the progression of
      demyelination.

PMID- 15733791
TI  - To smooth or not to smooth? ROC analysis of perfusion fMRI data.
AB  - Blood oxygenation level dependent (BOLD) contrast has been widely used for
      visualizing regional neural activation. Temporal filtering and parameter
      estimation algorithms are generally used to account for the intrinsic temporal
      autocorrelation present in BOLD data. Arterial spin labeling perfusion imaging is
      an emerging methodology for visualizing regional brain function both at rest and
      during activation. Perfusion contrast manifests different noise properties
      compared with BOLD contrast, represented by the even distribution of noise power
      and spatial coherence across the frequency spectrum. Consequently, different
      strategies are expected to be employed in the statistical analysis of functional
      magnetic resonance imaging (fMRI) data based on perfusion contrast. In this
      study, the effect of different analysis methods upon signal detection efficacy,
      as assessed by receiver operator characteristic (ROC) measures, was examined for
      perfusion fMRI data. Simulated foci of neural activity of varying amplitude and
      spatial extent were added to resting perfusion data, and the accuracy of each
      analysis was evaluated by comparing the results with the known distribution of
      pseudo-activation. In contrast to the BOLD fMRI, temporal smoothing or filtering
      reduces the power of perfusion fMRI data analyses whereas spatial smoothing is
      beneficial to the efficacy of analyses.

PMID- 15733792
TI  - A comparison of Gamma and Gaussian dynamic convolution models of the fMRI BOLD
      response.
AB  - Blood oxygenation level-dependent (BOLD) contrast-based functional magnetic
      resonance imaging (fMRI) has been widely utilized to detect brain neural
      activities and great efforts are now stressed on the hemodynamic processes of
      different brain regions activated by a stimulus. The focus of this paper is the
      comparison of Gamma and Gaussian dynamic convolution models of the fMRI BOLD
      response. The convolutions are between the perfusion function of the neural
      response to a stimulus and a Gaussian or Gamma function. The parameters of the
      two models are estimated by a nonlinear least-squares optimal algorithm for the
      fMRI data of eight subjects collected in a visual stimulus experiment. The
      results show that the Gaussian model is better than the Gamma model in fitting
      the data. The model parameters are different in the left and right occipital
      regions, which indicate that the dynamic processes seem different in various
      cerebral functional regions.

PMID- 15733793
TI  - Does T2-weighted MR imaging improve preoperative detection of malignant hepatic
      tumors? Observer performance study in 49 surgically proven cases.
AB  - The purpose of our study was to determine whether or not the addition of T2
      weighted fast spin-echo (SE) imaging to gadolinium-enhanced spoiled gradient
      recalled-echo (GRE) imaging improves the observer performance in the preoperative
      detection of malignant hepatic tumors. Gadolinium-enhanced GRE and fat-suppressed
      T2-weighted fast SE images obtained in 49 patients with 82 surgically confirmed
      malignant hepatic tumors (40 hepatocellular carcinomas and 42 metastases) were
      retrospectively reviewed by three independent off-site observers. In the random
      review of images, gadolinium-enhanced GRE images were reviewed first; thereafter,
      T2-weighted fast SE images were added for combined review. Observer performance
      was evaluated with the McNemar's test and receiver operating characteristic curve
      analysis. For gadolinium-enhanced GRE images alone vs. combined images,
      sensitivities for detection were 78% vs. 79% for hepatocellular carcinomas
      (P>.05), 67% vs. 71% for metastases (P<.05) and 72% vs. 75% for tumors overall
      (P<.05), respectively. The Az values were 0.892 vs. 0.889 in hepatocellular
      carcinomas (P>.05), 0.797 vs. 0.828 in metastases (P<.05) and 0.839 vs. 0.846 in
      tumors overall (P>.05), respectively. Our results showed that the addition of T2
      weighted fast SE imaging to gadolinium-enhanced GRE imaging improved the observer
      performance in the detection of metastases.

PMID- 15733794
TI  - Orientational dependence of trimethyl ammonium signal in human muscles by (1)H
      magnetic resonance spectroscopic imaging.
AB  - (1)H magnetic resonance spectroscopic imaging (MRSI) was used to investigate the
      effect of orientation on spectral characteristics of trimethyl ammonium (TMA) in
      human muscle at rest. Four different muscles in the healthy calf were studied:
      soleus, gastrocnemius, tibial posterior and anterior. The data demonstrate that
      muscle orientation can profoundly change apparent spectral characteristics of
      proton metabolites. In particular, muscle orientation can cause concerted changes
      in the spectral pattern of TMA/methyl (tCr) and methylene (Cr2) protons of
      creatine for a given muscle, a switch of TMA/tCr spectral patterns among
      different muscles and changes in the T(2) of TMA. A significant correlation was
      detected between TMA/tCr peaks and the Cr2 peak splitting (r=.62, P<.001). In
      vivo (1)H MRSI has the potential to simultaneously evaluate the orientation of
      muscle fibers and biochemical changes induced by a disease process or
      physiological activity.

PMID- 15733795
TI  - Magnetic resonance spectroscopy study of proton metabolite level changes in
      sensorimotor cortex after upper limb replantation-revascularization.
AB  - We aimed to investigate the changes in proton metabolite levels at the motor and
      somatosensory cortex by magnetic resonance spectroscopy (MRS) after upper
      extremity replantation or revascularization. Nine patients who referred to our
      clinic suffering from major total (two) and subtotal (seven) amputation of the
      upper extremity were enrolled in this study. Mean time value between the injury
      and operation was 5.1 h. Mean follow-up period or mean time between the injury
      and MRS analysis was 26.2 months (ranging from 7 to 41 months). Voxels (TR: 2000;
      TE: 136 ms) were placed onto locations in the bilateral precentral and
      postcentral cortex area of the cerebral hemispheres that represent the upper
      extremity. Contralateral sides of the brain hemisphere that represent the injured
      extremity were accounted as control groups. Metabolite ratios [NAA (N-acetyl
      aspartate)/Cr (creatine) and Cho (choline)/Cr] of the motor and somatosensory
      cortex were calculated. The NAA/Cr and Cho/Cr metabolite ratios between the two
      groups were found to be insignificant, and these results may indicate that there
      is no remarkable somatosensorial cortex disruption or demyelination in these
      patients. Fifty-six percent of patients were found as functional according to
      Chen's scale.

PMID- 15733796
TI  - Solitary mediastinal lymph node metastasis of hepatocellular carcinoma: MR
      imaging findings.
AB  - A 65-year-old man with multiple hepatocellular carcinomas in the liver with type
      C viral hepatitis had a solitary mediastinal lymph node metastasis in the right
      paratracheal to tracheobronchial region. Surgical resection for the mediastinal
      metastasis was undertaken based on magnetic resonance (MR) imaging findings,
      suggesting its radicality. We assess the MR imaging findings and presumable
      pathways of lymphatic metastasis from the liver to mediastinal lymph nodes in
      this report.

PMID- 15733797
TI  - MRI findings of gastric metastases from breast carcinoma.
AB  - We describe the MR appearance of breast cancer metastases to the stomach. The
      stomach wall was diffusely thickened with loss of the regular fold pattern best
      shown on the single shot T2-weighted images and enhanced with moderate mural
      enhancement on early and late post gadolinium images. The combination of gastric
      wall thickening and abnormal enhancement should suggest the diagnosis of diffuse
      mural metastases in a woman with a history of breast cancer.

PMID- 15733801
TI  - Re: Paroxetine in the treatment of severe non-dermatological pruritus.

PMID- 15733798
TI  - Re: Use of strong opioids in advanced cancer pain.

PMID- 15733802
TI  - The willingness of palliative care patients to participate in research.

PMID- 15733803
TI  - Morphine in intrasite gel applied topically to painful ulcers.

PMID- 15733804
TI  - Re: Olanzapine-induced delirium.

PMID- 15733805
TI  - Transformative aspects of caregiving at life's end.
AB  - We do not know to what extent the needs of caregivers involved with patients at
      the end of life are being met by care providers and whether caregiving at life's
      end can be a positive experience. We used the Hospice Experience Model of Care as
      a framework for understanding the effect of transformative tasks on caregiving at
      life's end. We compared current and bereaved caregivers and then, holding
      background characteristics constant, tested the independent effects of three
      transformative mediators: self-acceptance, meaning, and closure, as well as
      comfort with caregiving on several stressors when explaining differences in
      caregiver burden and gain. Transformative aspects of caregiving do not mediate
      the stressors associated with burden but do mediate one stressor associated with
      caregiver gain. Two mediators reduce caregiver burden and all four of the
      mediators improve caregiver gain. Caregivers who are able to attend to these
      transformative aspects find more gain in the caregiving experience.

PMID- 15733807
TI  - Status quo of palliative care in pediatric oncology-a nationwide survey in
      Germany.
AB  - Cancer is the leading cause of death among the pediatric population with life
      limiting conditions. The provision of palliative care at home and on the
      children's cancer unit has not been surveyed previously on a national scale. A
      survey of 71 (of 73) German pediatric oncology units (response rate 97%) provided
      information on the timing of breaking bad news, place of death, orchestrating
      palliative care at home and on the ward, integration of services and staff,
      funding of palliative care, bereavement services for siblings and parents,
      educational needs, level of self-satisfaction, and designated integrated
      palliative care services for children with cancer. More than 60% of children with
      malignancies died as inpatients in 2000, fewer than 40% at home. Twenty-nine
      pediatric cancer departments were able to provide comprehensive medical
      palliative home care, and nine units incorporate a designated palliative care
      team or person. Only half of the departments provide bereavement services for
      siblings. Many health professionals working on pediatric cancer units in Germany
      provide palliative home care in their free time without any payment. They
      predominantly use their private vehicles and often are unclear about the legal
      background and insurance arrangements covering their provision of care. The data
      suggest an important need for education about palliative and end-of-life care.
      The majority of children dying from cancer in Germany do not have access to
      comprehensive palliative care services at home. Our study highlights the
      necessity of incorporating the palliative paradigm into the care of children with
      cancer. Barriers to its implementation must be identified and overcome.

PMID- 15733808
TI  - Validation study of the korean version of the brief fatigue inventory.
AB  - The goal of this study was to evaluate the reliability and validity of the Korean
      version of the Brief Fatigue Inventory (BFI-K). One hundred seventy-eight cancer
      patients and the same number of age- and sex-matched control subjects completed
      the BFI-K, the European Organization for Research and Treatment of Cancer QLQ-C30
      (EORTC QLQ-C30), the Beck Depression Inventory (BDI), and a Brief Pain Inventory
      (BPI). The Cronbach's alpha coefficient for the BFI-K was 0.956 in the cancer
      patient group and 0.955 in the control group. The global score and nine of the
      single item scores for the BFI-K were significantly correlated with the fatigue
      and global health status/QoL subscale of the EORTC QLQ-C30, BDI, and BPI
      (coefficient range 0.38-0.66). Discriminant validity showed that BFI-K could
      distinguish significant differences of performance status between subgroups of
      patients, and between the cancer patient group and the control group, as
      expected. Our study has shown that the BFI-K is a reliable, valid self-rating
      instrument in terms of its psychometric properties.

PMID- 15733809
TI  - Predictors and Correlates of Fatigue in HIV/AIDS.
AB  - Variation in the intensity of fatigue according to selected demographic,
      cultural, and health/illness variables was explored in 372 patients with
      HIV/AIDS, and the contribution of fatigue to physical and mental health in this
      population was investigated within the UCSF Symptom Management Model (UCSF-SMM).
      The sample included 73% African Americans and 63% males. Moderate to severe
      fatigue intensity was reported by 58% of the total sample. Women, Hispanics, the
      disabled and those with inadequate income or insurance reported higher fatigue
      intensity scores. Two hierarchical regression models explored the contributions
      of fatigue to physical and mental health. Fatigue contributed 2% to the total
      variance (37.4%) in physical health, but did not contribute as an independent
      predictor of the total variance (23.2%) in mental health. The results of this
      study imply the need for further gender and ethnic-specific fatigue research, as
      well as symptom cluster research.

PMID- 15733806
TI  - The relationship of cancer symptom clusters to depressive affect in the initial
      phase of palliative radiation.
AB  - Research on comorbidity across cancer symptoms, including pain, fatigue, and
      depression, could suggest if crossover effects from symptom-specific
      interventions are plausible. Secondary analyses were conducted on a survey of 268
      cancer patients with recurrent disease from a northeastern U.S. city who were
      initiating palliative radiation for bone pain. Moderator regression analyses
      predicted variation in depressive affect that could be attributed to symptom
      clusters. Patients self-reported difficulty controlling each physical symptom
      over the past month on a Likert scale and depressive symptoms on a validated
      depression measure (Center for Epidemiologic Studies-Depression [CES-D]) over the
      past week on a four-category scale. An index of depressive affect was based on
      items of negative and positive affect from the CES-D. In predicting depressive
      affect, synergistic interactions of pain with fever, fatigue, and weight loss
      suggest separate pathways involving pain. A similar interaction with fever occurs
      when nausea was tested in place of pain. Further, the interaction between pain
      and fatigue is similar in form to the interaction between difficulty breathing
      and fatigue (when sleep is not a problem). Follow-up to the latter interaction
      reveals: 1) additional moderation by hypertension and palliative radiation to the
      hip/pelvis; and 2) a similar cluster not involving hypertension when appetite
      problems and weight loss were tested in place of fatigue. The significance and
      form of these interactions are remarkably consistent. Similar sickness mechanisms
      could be generating: 1) pain and nausea during fever; 2) pain and fatigue during
      weight loss; and 3) pain and breathing difficulty when fatigue is pronounced.
      Crossover effects from symptom-specific interventions appear promising.

PMID- 15733810
TI  - HIV/AIDS symptom management in Southern Africa.
AB  - We describe self-reported strategies used by persons living with HIV/AIDS in
      Botswana, Lesotho, South Africa, and Swaziland to manage common HIV-related
      symptoms. A questionnaire asked participants to list three to six symptoms they
      had recently experienced, the care strategies they had used to make them better,
      where they had learned the strategy, and to rate the perceived effectiveness of
      the strategy. Data were collected in 2002 from 743 persons. The self-care
      management strategies were coded into eight categories: medications,
      complementary treatments, self-comforting, changing diet, seeking help, exercise,
      spiritual care, and daily thoughts/activities. Overall, participants reported
      medications as the most frequently occurring management strategy and the most
      effective. A very small inventory of behavioral strategies was available to
      participants to help them manage their HIV-related symptoms.

PMID- 15733811
TI  - The risk of disciplinary action by state medical boards against physicians
      prescribing opioids.
AB  - Concern of physicians about being disciplined for prescribing opioids for
      patients in pain is one cause for undertreatment of pain. This study was done to
      assess the actual risk of being disciplined by state medical boards. A review of
      records of actions by the New York State Board for Professional Medical
      Misconduct for 3 years and of all medical boards in the United States for 9
      months was done to determine this risk. New York State, with 7.8% of U.S.
      physicians, had 10 physicians disciplined annually related to overprescribing
      opioids, while the total for the entire U.S. was 120 physicians annually. Most
      physicians disciplined had multiple violations in addition to overprescribing
      controlled substances. In the national sample, 43% were prescribing for
      themselves or for nonpatients, 12% prescribed for addicts without addressing the
      patients' problems of addiction, 42% had inadequate records, 19% prescribed
      without indication for opioids, 13% were incompetent in additional ways, and 8%
      were having sexual activity with patients. Not a single physician, for whom
      information was available, was disciplined solely for overprescribing opioids.
      The actual risk of an American physician being disciplined by a state medical
      board for treating a real patient with opioids for a painful medical condition is
      virtually nonexistent.

PMID- 15733812
TI  - The "pain pen" for breakthrough cancer pain: a promising treatment.
AB  - Breakthrough pain has been recognized as a challenging pain phenomenon in cancer.
      Oral transmucosal fentanyl citrate (OTFC) recently has been recommended as
      treatment, but OTFC is not widely available. Therefore, alternatives are needed.
      In two separate pilot studies, 58 patients were instructed to self-administer
      subcutaneous (SC) rescue opioids (hydromorphone (n=43), morphine (n=11), or
      sufentanil (n=4), using a standard injection-pen for breakthrough pain. Patients
      were asked to rate the overall efficacy of SC rescue opioids on a 3-point scale
      (not noticeable, moderate, or good). The efficacy was rated as good in 49
      patients (84%, 95% CI: 73-91%), moderate in 8 patients (14%), and not noticeable
      in 1 patient (2%). The median dose per injection was equianalgesic to 25 mg of SC
      morphine (range: 4-150 mg). Twenty-nine patients (50%) were treated until death
      (n=26) or were on ongoing treatment (n=3). Patients were treated for a median of
      6 weeks (1 day-41 months).

PMID- 15733813
TI  - Heart rate variability and the autonomic nervous system.

PMID- 15733814
TI  - The aldosterone antagonist and facultative diuretic eplerenone: a critical
      review.
AB  - Eplerenone is a new aldosterone-receptor blocker that differs from spironolactone
      by virtue of higher selectivity for the aldosterone receptor. Therefore,
      eplerenone treatment is associated with comparative and absolute low incidences
      of gynecomastia, mastodynia, and abnormal vaginal bleeding. Similarly, a lower
      incidence of sexual impotence than that associated with spironolactone
      administration may be anticipated. Eplerenone and spironolactone increase
      natriuresis and cause renal retention of potassium when plasma aldosterone is
      high, i.e., both agents are facultative diuretics. Eplerenone reduces high blood
      pressure effectively. The results of a recent large study and an ensuing meta
      analysis on antihypertensive treatment suggest that a diuretic should be the
      first-choice agent in most circumstances. Low-dose eplerenone combinations with a
      low-dose thiazide-type diuretic appear to be options worth investigating, since
      the overall cardiovascular benefit brought about by reducing blood pressure with
      the thiazide would be increased, inter alia, by the antikaliuretic action and by
      the blockade of extrarenal aldosterone receptors provoked by eplerenone.
      Eplerenone should replace spironolactone as a natriuretic and antikaliuretic in
      heart failure and as add-on treatment in severe systolic cardiac insufficiency,
      and it is indicated after an acute myocardial infarction complicated by left
      ventricular dysfunction and heart failure. The finding that hypertension control
      with diuretic-based pharmacotherapy results in better prevention of heart failure
      than pressure reduction with other drugs makes it pertinent to investigate
      whether diuretics in general, and eplerenone in particular, should constitute
      part of the initial pharmacotherapy for heart failure when there is no overt
      fluid retention and independent of the etiology. Eplerenone may cause
      hyperkalemia, and it might favor the development of metabolic acidosis or
      hyponatraemia in some circumstances.

PMID- 15733815
TI  - Heart rate variability: from bench to bedside.
AB  - Power spectrum analysis of cardiovascular signal variability, and in particular
      of the RR period (heart rate variability, HRV), is a widely used methodology for
      investigating autonomic neural regulation in health and disease that can quantify
      the sympathovagal balance modulating the sinus node pacemaker. In some cases, it
      can also quantify the neural regulation of other organs or apparatuses. However,
      use of the correct methodology is crucial to extract the information embedded in
      the frequency domain. In numerous abnormal conditions, such as essential arterial
      hypertension, acute myocardial infarction and heart failure, the sympathovagal
      balance may be altered in basal conditions. However, a reduced responsiveness to
      an excitatory stimulus is the most common feature that characterizes numerous
      pathophysiological states. The attenuation of an oscillatory pattern can also
      reflect an altered target function, thus providing important prognostic markers.
      The general features of this approach correspond well to the needs of an
      internist attempting to envisage the involvement of the whole organism in a
      disease process.

PMID- 15733816
TI  - What can we learn from undergraduate medical education?
AB  - As in undergraduate medical training, postgraduate training of medical
      specialists requires clear learning objectives, a structured learning process, a
      challenging learning environment, valid and reliable assessment procedures, and
      an effective learning organization. One may wonder, however, whether such a
      structured approach is more theory than practice in the majority, if not all,
      teaching hospitals involved in graduate medical education.

PMID- 15733817
TI  - Influence of acute exacerbation of chronic obstructive pulmonary disease or
      congestive heart failure on functional decline after hospitalization in
      nonagenarian patients.
AB  - BACKGROUND: The functional decline that follows hospitalization may be especially
      important in frail populations such as nonagenarians. The present study examined
      the functional decline among nonagenarians admitted because of exacerbations of
      chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF).
      METHODS: A prospective cohort study was performed on two groups of patients who
      were distinguished by diagnosis in two tertiary academic medical hospitals. Sixty
      nonagenarian patients, admitted because of exacerbation of COPD (n=30) or CHF
      (n=30), were evaluated at admission, upon discharge, and 3 months post
      hospitalization. The Barthel Index (BI) was used to assess functionality. The
      outcome we were interested in was functional decline 3 months after hospital
      discharge. RESULTS: The inpatient mortality rate was 10%. Overall functional
      status at discharge, as compared with that before admission, declined in all 54
      surviving patients (p<0.001). At the 3-month follow-up, 37 patients were
      evaluated; a decline in their BI persisted in 60% of them. We did not find
      significant differences, either upon discharge or at 3 months post
      hospitalization, in the decrease in BI rate between COPD patients and CHF
      patients. CONCLUSIONS: The fact that the underlying disease does not induce
      differences in the functional outcome of nonagenarians reinforces the importance
      of using a comprehensive approach at admission and after discharge for all frail
      patients.

PMID- 15733818
TI  - Dysglycemia in suspected acute coronary syndromes.
AB  - BACKGROUND: Apart from diabetes itself, even minor glycometabolic dysregulation
      may be associated with an increased risk of cardiovascular disease. We analyzed
      the prevalence and predictive value of glycometabolic disturbances in patients
      with a suspected acute coronary syndrome (ACS). METHODS: In a prospective follow
      up study, admission glucose and Hba1C levels in all consecutive patients with
      suspected ACS were measured. Dysglycemia was defined as a Hba1C of 5.6-6.1% with
      a non-fasting glucose above 7.8 mmol/L. Both predictors of glycometabolic
      disturbances and the predictive value of glycometabolic disturbances were
      studied. RESULTS: Of the 521 patients with a suspected ACS who were included in
      the study, 332 (64%) had an ACS and 189 (36%) had atypical chest pain. A total of
      115 patients (22%) had diabetes and 65 (13%) had dysglycemia. Patients with
      diabetes or dysglycemia had an increased risk of a confirmed diagnosis of ACS (RR
      2.3, 95% CI 1.5-3.4). Multivariate analyses did not change these findings.
      CONCLUSIONS: One in three patients with suspected ACS had a glucose metabolism
      disturbance. Glycometabolic disturbance was strongly associated with a confirmed
      diagnosis of ACS. Whether intensive treatment of patients with disturbed glucose
      metabolism may improve long-term prognosis needs to be assessed.

PMID- 15733819
TI  - Screening for carotid artery disease in the general public.
AB  - BACKGROUND: Screening for various diseases is now being offered to the public in
      settings other than their physicians' office, often using expensive and
      sophisticated technology. Little is known about how patients decide to
      participate in such programs, whether they understand the implications of a
      positive or negative test, or if their primary care physician is involved in the
      decision to screen. METHODS: We surveyed a cohort of patients who participated in
      a free carotid artery screening using Doppler ultrasound at a tertiary care
      academic medical center. RESULTS: One hundred twenty-four patients participated
      and underwent the ultrasound exam. Their mean age was 68.8 (+/-9.8) years and 54%
      were female. Some 117 patients (94%) completed the survey. Five patients (4%)
      tested positive for significant carotid artery stenosis. Sixty-two percent (95%
      CI: 53-71%) of the patients learned about the program through a newspaper
      advertisement. Eighty-eight percent (95% CI: 82-94%) of the subjects stated that
      their primary physician had not suggested that they have the test, and 59% (95%
      CI: 50-68%) did not know that carotid artery surgery is often recommended for
      patients who test positive. CONCLUSIONS: This study of one group of patients who
      voluntarily took a screening test for carotid artery stenosis raises some
      important questions since most subjects did not understand the implications of a
      positive result, nor did they involve their physicians in their decision to take
      the test. Further studies are needed to evaluate whether providing patients with
      more information about the implications of a screening test would change their
      desire to have the test and about the nature of the informed consent required
      before such screening is carried out.

PMID- 15733820
TI  - The annual yield of diagnostic endoscopy of the lower digestive tract.
AB  - BACKGROUND: Endoscopy of the colon and rectum has become a standard diagnostic
      procedure. No data are presented in the literature on the annual yield or on
      morbidity patterns. A large, cross-sectional, single-center study was done in
      order to detect the annual yield of endoscopy of the colon and rectum. METHODS:
      All consecutive endoscopies performed over an 11-year period were included. All
      files from a random year were taken in order to collect data on the indication
      for the endoscopy. A standardized endoscopy report was used. RESULTS: Over the 11
      year period, 11,550 consecutive endoscopies of the lower digestive tract were
      performed. Seven hundred and fourteen procedures were excluded because they were
      done as a direct follow-up after the index procedure. The majority of endoscopies
      were scheduled as colonoscopy. The most common endoscopic diagnoses made each
      year remained constant in number. Cancer was diagnosed in 4-6% of cases,
      inflammation in 9-15%, polyps in 9-16%, and diverticular disease in 21-37%. The
      percentage of women undergoing the procedure each year ranged from 54% to 59%,
      that of men from 41% to 46%. CONCLUSION: From this study it can be concluded that
      the annual yield of endoscopy of the lower digestive tract remains rather
      constant. No major changes in morbidity are noted.

PMID- 15733821
TI  - Distinguishing between ischemic and non-ischemic dilated cardiomyopathy based on
      non-invasive ultrasonic evaluation of peripheral arteries.
AB  - BACKGROUND: Recently, high-frequency transducers have been introduced in
      echocardiography laboratories to non-invasively evaluate peripheral arteries. Our
      aim was to assess the usefulness of these non-invasive vascular ultrasonic
      techniques in differentiating between ischemic and non-ischemic dilated
      cardiomyopathy. METHODS: Forty patients with dilated cardiomyopathy of uncertain
      origin who underwent echocardiographic examination were studied. In all patients,
      carotid, femoral, and brachial arteries were scanned using high-frequency
      transducers in order to detect atherosclerotic plaques and to measure intima
      media wall thickness. Also, flow-mediated vasodilation was measured at the
      brachial artery. RESULTS: Of the 40 patients studied, 24 (60%) had significant
      coronary lesions. In patients with ischemic cardiomyopathy, carotid plaques were
      found more frequently (79% vs. 25%, p=0.001), and intima-media wall thickness was
      higher in carotid (1.14+/-0.23 vs. 0.84+/-0.20 mm, <0.001), femoral (1.21+/-0.15
      vs. 0.90+/-0.17 mm, p<0.001), and brachial (0.85+/-0.11 vs. 0.68+/-0.12, p<0.001)
      arteries. Carotid intima-media thickness of 1 mm or more was 83% sensitive and
      69% specific for the diagnosis of ischemic cardiomyopathy. The highest diagnostic
      accuracy for any isolated vascular finding was obtained for femoral intima-media
      thickness greater than 1.1 mm (83% sensitivity, 88% specificity) and for brachial
      intima-media thickness greater than 0.7 mm (88% sensitivity and 81% specificity).
      The highest sensitivity (92%) was obtained for the presence of 1 or more vascular
      findings, and the highest specificity (94%) for 3 or more vascular findings.
      CONCLUSION: Non-invasive assessment of peripheral arteries is of help in
      differentiating between ischemic and non-ischemic dilated cardiomyopathy. These
      ultrasonic techniques should be considered as complementary examinations in the
      evaluation of patients with dilated cardiomyopathy in echocardiography
      laboratories.

PMID- 15733822
TI  - Prognostic value of inflammatory markers alone and in combination with blood
      lipids in patients with stable coronary artery disease.
AB  - BACKGROUND: Biomarkers may be helpful in improving risk stratification in
      cardiovascular diseases. Therefore, we assessed the prognostic value of sensitive
      inflammatory markers alone and in combination with lipids in patients with stable
      coronary artery disease (CAD). METHODS: In a prospective cohort study, we
      recruited 312 patients, aged 40-68 years, with angiographically proven,
      clinically stable CAD at the University Hospital in Ulm, Germany. C-reactive
      protein (CRP), interleukin-6 (IL-6), and lipoproteins were measured at baseline
      in all patients. After a median follow-up of 3.2 years, a fatal or non-fatal
      cardiovascular event (CVE) had occurred in 60 of 300 patients (20%). RESULTS:
      Baseline concentrations of IL-6 were significantly higher (3.27 versus 2.45
      pg/ml, p=0.02) in patients with a future CVE compared to those without. After
      multivariate adjustment, patients with elevated baseline concentrations (4th
      versus 1st quartile) of inflammatory markers showed a moderately increased risk
      of CVE, i.e., hazard ratios (HR) were 1.3 (95% confidence interval 0.6-2.8) for
      CRP and 1.8 (0.9-3.6) for IL-6. The HRs increased if both inflammatory and lipid
      markers were simultaneously elevated (both markers>median versus<median). HR was
      1.8 (0.8-4.0) for simultaneously elevated baseline concentrations of CRP and
      total cholesterol, and 1.9 (0.8-4.7) for simultaneously elevated concentrations
      of CRP and LDL cholesterol. Corresponding HRs for IL-6 and lipoproteins were 2.0
      (0.9-2.7) and 2.1 (0.9-5.0). CONCLUSION: Simultaneous assessment of markers of
      inflammation and lipid metabolism may improve cardiovascular risk stratification
      in patients with stable CAD.

PMID- 15733823
TI  - Disseminated Mycobacterium avium complex infection in a renal transplant patient.
AB  - Organ transplant recipients are at an increased risk of developing opportunistic
      infections due to prolonged immunosuppression. We present the case of a renal
      transplant recipient with severe CD4 lymphopenia who developed disseminated
      Mycobacterium avium complex infection. Recovery from infection was paralleled by
      a progressive increase in CD4 lymphocytes. T lymphocyte subsets are not monitored
      routinely in organ transplants but may identify patients at risk of developing
      serious infectious complications.

PMID- 15733824
TI  - A rare lung manifestation with rapidly progressive glomerulonephritis (RPGN).
AB  - In this unusual case, we report the history of a patient who was hospitalized
      with pulmonary manifestations presenting as broncholitis obliterance organizing
      pneumonia (BOOP) associated with ANCA-negative pauci-immune glomerulonephritis.
      Other known causes for the occurrence of BOOP were excluded. Immediate diagnosis
      and treatment with a combination of steroids and cytotoxic therapy resulted in a
      complete remission and prevented eventual dialysis.

PMID- 15733825
TI  - Henoch-Schonlein purpura associated with Aloe vera administration.
AB  - Henoch-Schonlein purpura (HSP) is a systemic vasculitis that occurs most often in
      children and rarely follows exposure to drugs or other environmental factors.
      Aloe is one of the most widely used traditional remedies and has been associated
      with gastrointestinal and renal complications. We report a case of HSP in an
      adult patient who had previously received the herb Aloe vera.

PMID- 15733826
TI  - Coumadin-induced hepatitis.
AB  - The diagnosis of "coumadin-induced hepatitis" is compatible with the time
      relationship between the start of the drug and the onset of hepatopathy, the
      rapid improvement following discontinuation of the drug, recurrence of liver
      dysfunction after re-exposure to the drug and liver histology. Although liver
      damage induced by coumadin derivatives is rare, it is important to be aware of
      the hepatotoxic potential of these drugs, which, in most cases, mimic the
      clinical presentation of viral hepatitis.

PMID- 15733827
TI  - The patient's history remains a powerful tool in the diagnosis of fever of
      unknown origin.

PMID- 15733828
TI  - Pancreatic carcinoma and basal cell carcinoma secondary to Hodgkin's disease
      treatment.

PMID- 15733829
TI  - Transcriptional signaling by double-stranded RNA: role of TLR3.
AB  - Mammalian Toll-like receptors recognize components of invading microbes and
      trigger the first line of innate immune response that is mediated by
      transcriptional induction of a large number of cellular genes. Toll-like receptor
      3 (TLR3) is thought to be a major mediator of cellular response to viral
      infection, because it responds to double-stranded (ds) RNA, a common by-product
      of viral replication. This article is focused on the nature of the signaling
      pathways activated by TLR3 and dsRNA. The genes induced by TLR3 activation
      include those that encode secreted antiviral cytokines, such as interferon (IFN),
      and those that encode intracellular viral stress-inducible proteins. Recent
      studies have revealed several unique features of TLR3 signaling that are
      highlighted here. Specifically, we discuss the roles of receptor tyrosine
      phosphorylation, PI3 kinase and two-step activation of the transcription factors,
      IRF-3 and NF-kappaB, in mediating TLR3-signaling.

PMID- 15733830
TI  - Dual role for TGF-beta1 in apoptosis.
AB  - The exposure of cells to TGF-beta1 can trigger a variety of cellular responses
      including the inhibition of cell growth, migration, differentiation and
      apoptosis. TGF-beta1-regulated apoptosis is cell type and context-dependent,
      indeed TGF-beta1 provides signals for both cell survival or apoptosis. The
      molecular mechanisms underlying the role of TGF-beta1 in apoptosis remains
      unclear. The proteins that primarily mediate the intracellular signaling of TGF
      beta1 are the members of the Smad family. Nevertheless, TGF-beta1 signaling can
      also cooperate with the death receptor apoptotic pathway (Fas, TNF), with the
      intracellular modulators of apoptosis JNK and p38 MAP kinases, Akt, NF-kappaB,
      and with the mitochondrial apoptotic pathway mediated by members of the Bcl-2
      family. Moreover, the involvement of TGF-beta1 in the production of oxidative
      stress and in preventing the inflammatory processes required for the clearance of
      apoptotic bodies is further evidence of its integration into apoptotic pathways.
      The interaction and balance between different stimuli provides the basis for the
      pro- or anti-apoptotic output of TGF-beta1 signaling in a given cell.

PMID- 15733831
TI  - Tumor necrosis factor, cancer and anticancer therapy.
AB  - Tumor necrosis factor (TNF) is being utilized as an antineoplastic agent for the
      treatment of patients with locally advanced solid tumors. However, its role in
      cancer therapy is debated. Although a large body of evidence supports TNF's
      antineoplastic activity, the cascade of molecular events underlying TNF-mediated
      tumor regression observed in vivo is still incompletely elucidated. Intriguingly,
      some pre-clinical findings suggest that TNF may promote cancer development and
      progression, which has led to propose anti-TNF therapy as a novel approach to
      malignancies. In the present work, we summarize the molecular biology of TNF with
      particular regard to its tumor-related properties, and review the experimental
      and clinical evidence currently available describing the complex and sometime
      conflicting relationship between this cytokine, cancer and antitumor therapy.
      Recent insights that might pave the way to further exploitation of the
      antineoplastic potential of TNF are also discussed.

PMID- 15733832
TI  - Tumor therapeutics by design: targeting and activation of death receptors.
AB  - Due to their strong apoptosis-inducing capacity, the death receptor ligands
      CD95L, TNF and TRAIL have been widely viewed as potential cancer therapeutics.
      While clinical data with CD95L and TRAIL are not yet available, TNF is a
      registered drug, albeit only for loco-regional application in a limited number of
      indications. The TNF experience has told us that specific delivery and restricted
      action is a major challenge in the development of multifunctional,
      pleiotropically acting cytokines into effective cancer therapeutics. Thus, gene
      therapeutic approaches and new cytokine variants have been designed over the last
      10 years with the aim of increasing anti-tumoral activity and reducing systemic
      side effects. Here, we present our current view of the therapeutic potential of
      the death receptor ligands TNF, CD95L and TRAIL and of the progress made towards
      improving their efficacy by tumor targeting, use of gene therapy and genetic
      engineering. Results generated with newly designed fusion proteins suggest that
      enhanced tumor-directed activity and prevention of undesirable actions of death
      receptor ligands is possible, thereby opening up a useful therapeutic window for
      all of the death receptor ligands, including CD95L.

PMID- 15733834
TI  - Viral chemokine-modulatory proteins: tools and targets.
AB  - The chemokine network is an extensive system that regulates many immune functions
      such as leukocyte locomotion, T cell differentiation, angiogenesis and mast cell
      degranulation. Tight control of chemokines is vital for proper immune function.
      Not surprisingly, viruses have found ways to subvert or exploit the immune system
      in order to persist in co-existence with their hosts. Several viral immune
      evasion genes encode proteins that modulate the chemokine network. We attempt to
      identify which aspects of the chemokine control mechanisms are susceptible to
      modulation. Chemokine-glycosaminoglycan interaction, extracellular processing of
      chemokines and chemokine scavenging will be discussed in the light of poxvirus
      and herpesvirus immune evasion. Viral chemokine-modulatory proteins may either be
      targets for anti-viral therapy or lead the way to new anti-inflammatory chemokine
      modulating drugs.

PMID- 15733833
TI  - Transcriptional regulation of vascular endothelial growth factor in cancer.
AB  - Vascular endothelial growth factor (VEGF) is critical for vascularization of
      tissues, including tumors, making it an attractive target for controlling
      angiogenesis. An important first step towards the goal of effectively blocking
      tumor angiogenesis is to understand the relationships among tumor-promoting
      molecules. Whereas little is known about developmental regulation of VEGF,
      pathological regulation of VEGF during disease states and tumorigenesis is better
      understood. This review focuses on transcriptional regulation of VEGF expression
      in cancer. Understanding how VEGF is regulated in tumors cells may provide the
      basis for future treatments that target both the tumor and its vascular supply.

PMID- 15733835
TI  - Chauvinism in science.

PMID- 15733836
TI  - Ribosome inactivating proteins and apoptosis.
AB  - Ribosome inactivating proteins (RIPs) are protein toxins that are of plant or
      microbial origin that inhibit protein synthesis by inactivating ribosomes. Recent
      studies suggest that RIPs are also capable of inducing cell death by apoptosis.
      Though many reports are available on cell death induced by RIPs, the mechanism
      involved is not well studied. Comparison of pathways of apoptosis and cellular
      events induced by various RIPs suggests a central role played by mitochondria,
      probably acting as an integrator of cellular stress and cell death. The purpose
      of this review is to compare the various apoptotic pathways that may be involved
      and propose a general pathway in RIP-induced cell death.

PMID- 15733837
TI  - GC-MS libraries for the rapid identification of metabolites in complex biological
      samples.
AB  - Gas chromatography-mass spectrometry based metabolite profiling of biological
      samples is rapidly becoming one of the cornerstones of functional genomics and
      systems biology. Thus, the technology needs to be available to many laboratories
      and open exchange of information is required such as those achieved for
      transcript and protein data. The key-step in metabolite profiling is the
      unambiguous identification of metabolites in highly complex metabolite
      preparations with composite structure. Collections of mass spectra, which
      comprise frequently observed identified and non-identified metabolites, represent
      the most effective means to pool the identification efforts currently performed
      in many laboratories around the world. Here, we describe a platform for mass
      spectral and retention time index libraries that will enable this process (MSRI;
      www.csbdb.mpimp-golm.mpg.de/gmd.html). This resource should ameliorate many of
      the problems that each laboratory will face both for the initial establishment of
      metabolome analysis and for its maintenance at a constant sample throughput.

PMID- 15733838
TI  - The "promiscuous drug concept" with applications to Alzheimer's disease.
AB  - Arguably, Alzheimer's disease (AD) is a multifactorial syndrome, rather than
      single disease, arising from a complex array of neurochemical factors. Numerous
      studies on the molecular pathogenesis of AD implicate a diversity of factors
      ranging from neurotoxic peptides (beta-amyloid) to inflammatory processes
      (interleukins), but all culminating in a common neuropathology. This diversity of
      molecular causation is an impediment to the design of effective therapies for AD.
      To address this design problem, we sought to identify a single, common motif (a
      "common receptor") shared by multiple structurally and functionally diverse
      proteins implicated in AD. This search revealed the presence of a common BBXB
      peptide motif and upon refinement, an AXBBXB motif; these regions can be
      exploited for the design of a "promiscuous drug" that exploits a "one-drug
      multiple-receptors" therapeutic strategy for AD.

PMID- 15733839
TI  - At least two Toc34 protein import receptors with different specificities are also
      present in spinach chloroplasts.
AB  - The receptor components of the chloroplast protein import machinery, Toc34 and
      Toc159, are both encoded by small gene families in Arabidopsis thaliana. Recent
      results suggest that each member of these families preferentially interacts with
      different groups of precursor proteins. Here we address the question, whether
      multiple homologous Toc receptors are unique to Arabidopsis or whether they are a
      general phenomenon in plants. Indeed, in spinach we could identify at least two
      Toc34 proteins with different substrate specificities as demonstrated by
      competition and antibody inhibition experiments. In addition, an analysis of the
      available genomic data revealed the presence of at least two Toc34 homologs in
      six other plant species.

PMID- 15733840
TI  - Werner syndrome protein associates with gamma H2AX in a manner that depends upon
      Nbs1.
AB  - The WRN protein is mutated in the chromosomally unstable Werner syndrome (WS) and
      the Nbs1 protein is mutated in Nijmegen breakage syndrome (NBS). The Nbs1 protein
      is an integral component of the M/R/N complex. Although WRN is known to interact
      with this complex in response to gamma-irradiation, the mechanism of action is
      unclear. Here, we show that WRN co-localizes and associates with gamma H2AX, a
      marker protein of DNA double strand breaks (DSBs), after cellular exposure to
      gamma-irradiation. While the DNA damage-inducible Nbs1 foci formation is normal
      in WS cells, WRN focus formation is defective in NBS cells. Consistent with this,
      gamma H2AX colocalizes with Nbs1 in WS cells but not with WRN in NBS cells. The
      defective WRN-gamma H2AX association in NBS cells can be complemented with wild
      type Nbs1, but not with an Nbs1 S343A point mutant that lacks an ATM
      phosphorylation site. WRN associates with H2AX in a manner dependent upon the
      M/R/N complex. Our results suggest a novel pathway in which Nbs1 may recruit WRN
      to the site of DNA DSBs in an ATM-dependent manner.

PMID- 15733841
TI  - Characterisation of plant tocopherol cyclases and their overexpression in
      transgenic Brassica napus seeds.
AB  - Tocopherols, collectively known as vitamin E, are only synthesised in
      photosynthetic organisms. Tocopherol cyclase (TC) catalyses the formation of the
      chromanol headgroup of the various tocopherol isoforms. TCs from Arabidopsis and
      maize (Zea mays) were expressed in Escherichia coli and purified. Analysis of the
      enzymatic properties revealed similarities but also differences between the two
      enzymes. Overexpression of chimeric TC gene constructs in developing seeds of
      transgenic rapeseed plants enhanced and modified the relative abundance of
      individual tocochromanol species in the seed oil, indicating a regulatory
      function of the enzyme in prenyllipid metabolism.

PMID- 15733842
TI  - Screening of genes expressed in developing mandibles during soldier
      differentiation in the termite Hodotermopsis sjostedti.
AB  - We investigated the morphological changes accompanying soldier differentiation in
      the damp-wood termite Hodotermopsis sjostedti. Genes expressed in the developing
      mandibles, which undergo the most remarkable morphological changes during soldier
      differentiation, were screened using fluorescent differential display. Database
      searches for sequence similarities were conducted and the relative expression
      levels were then quantified by real-time polymerase chain reaction. Among the
      identified candidate genes, 12 genes were upregulated during soldier
      differentiation. These included genes for cuticle proteins, nucleic acid binding
      proteins, ribosomal proteins and actin-binding protein, which were inferred to be
      involved in caste-specific morphogenesis in termites.

PMID- 15733843
TI  - Tau protein binds single-stranded DNA sequence specifically--the proof obtained
      in vitro with non-equilibrium capillary electrophoresis of equilibrium mixtures.
AB  - Tau is a microtubule-associated protein, which plays an important role in
      physiology and pathology of neurons. Tau has been recently reported to bind
      double-stranded DNA (dsDNA) but not to bind single-stranded DNA (ssDNA) [Cell.
      Mol. Life Sci. 2003, 60, 413-421]. Here, we prove that tau binds not only dsDNA
      but also ssDNA. This finding was facilitated by using two kinetic capillary
      electrophoresis methods: (i) non-equilibrium capillary electrophoresis of
      equilibrium mixtures (NECEEM); (ii) affinity-mediated NECEEM. Using the new
      approach, we observed, for the first time, that tau could induce dissociation of
      strands in dsDNA by binding one of them in a sequence-specific fashion. Moreover,
      we determined the equilibrium dissociation constants for all tau-DNA complexes
      studied.

PMID- 15733844
TI  - Structure of a type II thymidine kinase with bound dTTP.
AB  - The structure of human cytosolic thymidine kinase in complex with its feedback
      inhibitor 2'-deoxythymidine-5'-triphosphate was determined. This structure is the
      first representative of the type II thymidine kinases found in several pathogens.
      The structure deviates strongly from the known structures of type I thymidine
      kinases such as the Herpes simplex enzyme. It contains a zinc-binding domain with
      four cysteines complexing a structural zinc ion. Interestingly, the backbone
      atoms of the type II enzyme bind thymine via hydrogen-bonds, in contrast to type
      I, where side chains are involved. This results in a specificity difference
      exploited for antiviral therapy. The presented structure will foster the
      development of new drugs and prodrugs for numerous therapeutic applications.

PMID- 15733845
TI  - Ser475, Glu272, Asp276, Asp327, and Asp360 are involved in catalytic activity of
      human tripeptidyl-peptidase I.
AB  - Tripeptidyl-peptidase I (TPP I) is a lysosomal aminopeptidase that sequentially
      removes tripeptides from small polypeptides and also shows a minor endoprotease
      activity. Mutations in TPP I are associated with a fatal lysosomal storage
      disorder--the classic late-infantile form of neuronal ceroid lipofuscinoses. In
      the present study, we analyzed the catalytic mechanism of the human enzyme by
      using a site-directed mutagenesis. We demonstrate that apart from previously
      identified Ser475 and Asp360, also Glu272, Asp276, and Asp327 are important for
      catalytic activity of the enzyme. Involvement of serine, glutamic acid, and
      aspartic acid in the catalytic reaction validates the idea, formulated on the
      basis of significant amino acid sequence homology and inhibition studies, that
      TPP I is the first mammalian representative of a growing family of serine
      carboxyl peptidases.

PMID- 15733846
TI  - Discovery of quinazolinone and quinoxaline derivatives as potent and selective
      poly(ADP-ribose) polymerase-1/2 inhibitors.
AB  - Two classes of quinazolinone derivatives and quinoxaline derivatives were
      identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1)
      and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant
      PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high
      selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity
      for PARP-2. SBDD analysis via a combination of X-ray structural study and
      homology modeling suggested distinct interactions of inhibitors with PARP-1 and
      PARP-2. These findings provide a new structural framework for the design of
      selective inhibitors for PARP-1 and PARP-2.

PMID- 15733847
TI  - Stopped-flow spectrophotometric and resonance Raman analyses of aldoxime
      dehydratase involved in carbon-nitrogen triple bond synthesis.
AB  - On stopped-flow analysis of aliphatic aldoxime dehydratase (OxdA), a novel
      hemoprotein, a spectrum derived from a reaction intermediate was detected on
      mixing ferrous OxdA with butyraldoxime; it gradually changed into that of ferrous
      OxdA with an isosbestic point at 421 nm. The spectral change on the addition of
      butyraldoxime to the ferrous H320A mutant showed the formation of a substrate
      coordinated mutant, the absorption spectrum of which closely resembled that of
      the above intermediate. These observations and the resonance Raman investigation
      revealed that the substrate actually binds to the heme in OxdA, forming a hexa
      coordinate low-spin heme.

PMID- 15733848
TI  - Effects of different anti-tau antibodies on tau fibrillogenesis: RTA-1 and RTA-2
      counteract tau aggregation.
AB  - Tau is the major antigenic component of neurofibrillary pathology in tauopathy,
      including Alzheimer's disease. Although conversion of soluble tau to an insoluble
      polymerized fibrillar form is a key factor in the pathogenesis of tauopathy, the
      mechanism of the change is unclear and no inhibitors of fibril formation are
      available. Monoclonal antibodies against the 1st or 2nd repeat of the microtubule
      binding domain, but not the C-terminal 16 residues, completely inhibited tau
      aggregation into PHF. Furthermore, they did not inhibit tau-induced tubulin
      assembly. Thus, they are useful to investigate tau protein conversion and will be
      useful therapeutic lead materials.

PMID- 15733849
TI  - Characterisation of a novel amylosucrase from Deinococcus radiodurans.
AB  - The BLAST search for amylosucrases has yielded several gene sequences of putative
      amylosucrases, however, with various questionable annotations. The putative
      encoded proteins share 32-48% identity with Neisseria polysaccharea amylosucrase
      (AS) and contain several amino acid residues proposed to be involved in AS
      specificity. First, the B-domains of the putative proteins and AS are highly
      similar. In addition, they also reveal additional residues between putative beta
      strand 7 and alpha-helix 7 which could correspond to the AS B'-domain, which
      turns the active site into a deep pocket. Finally, conserved Asp and Arg residues
      could form a salt bridge similar to that found in AS, which is responsible for
      the glucosyl unit transfer specificity. Among these found genes, locus
      NP_294657.1 (dras) identified in the Deinococcus radiodurans genome was initially
      annotated as an alpha-amylase encoding gene. The putative encoded protein (DRAS)
      shares 42% identity with N. polysaccharea AS. To investigate the activity of this
      protein, gene NP_294657.1 was cloned and expressed in Escherichia coli. When
      acting on sucrose, the pure recombinant enzyme was shown to catalyse insoluble
      amylose polymer synthesis accompanied by side-reactions (sucrose hydrolysis,
      sucrose isomer and soluble maltooligosaccharide formation). Kinetic analyses
      further showed that DRAS follows a non-Michaelian behaviour toward sucrose
      substrate and is activated by glycogen, as is AS. This demonstrates that gene
      NP_294657.1 encodes an amylosucrase.

PMID- 15733850
TI  - Inhibition of human telomerase by oligonucleotide chimeras, composed of an
      antisense moiety and a chemically modified homo-oligonucleotide.
AB  - Most tumor cells attain their immortality by reactivating telomerase. We report
      here the telomerase inhibitory potential of chimeric oligonucleotides composed of
      a 13mer antisense sequence targeting the telomerase RNA template region and a
      (s4dU)n moiety at its 3' or 5'-end. The increase of the thiolated chain length
      enhances the telomerase inhibitory potential, but decreases specificity,
      indicated by HIV reverse transcriptase inhibition. Chimeras with 5' (s4dU)(n)s
      were more potent inhibitors than the antisense alone or the 3' modified ones. Cy5
      labeled (s4dU)4AS and (s4dU)8AS proved the internalization of the
      oligonucleotides, raising the possibility to be tested as cellular anti
      telomerase agents.

PMID- 15733851
TI  - Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1
      substrate.
AB  - Recent work has shown that the LKB1 tumour suppressor protein kinase
      phosphorylates and activates protein kinases belonging to the AMP activated
      kinase (AMPK) subfamily. In this study, we identify the sucrose non-fermenting
      protein (SNF1)-related kinase (SNRK), a largely unstudied AMPK subfamily member,
      as a novel substrate for LKB1. We demonstrate that LKB1 activates SNRK by
      phosphorylating the T-loop residue (Thr173), and that the LKB1 regulatory
      subunits STRAD and MO25 are required for LKB1 to activate SNRK. We find that SNRK
      is not active when expressed in HeLa cells that lack expression of LKB1, and its
      activity is restored by expression of wild type LKB1, but not catalytically
      deficient LKB1. We also present evidence that two other AMPK-related kinases more
      distantly related to AMPK than SNRK, namely NIM1 and testis-specific
      serine/threonine kinase-1 (TSSK1) are not substrates for LKB1. Tissue
      distribution analysis indicates that SNRK protein is mainly expressed in testis,
      similar to TSSK isoforms, whereas NIM1 is more widely expressed. These results
      provide evidence that SNRK could mediate some of the physiological effects of
      LKB1.

PMID- 15733852
TI  - Regulation of the transcription factor, CTCF, by phosphorylation with protein
      kinase CK2.
AB  - CTCF is a transcription factor involved in various aspects of gene regulation. We
      previously reported that CTCF function is modulated by protein kinase CK2. In
      this report we investigate further the role of CK2 in regulating the
      transcriptional properties of CTCF. We demonstrate that coexpression of CTCF with
      CK2 switches function of CTCF from repressor to activator. The non
      phosphorylatable mutant increases repression by CTCF and potentiates the growth
      suppressive ability of the protein, whereas the phospho-mimetic mutant behaves in
      the opposite fashion. Mutation of the individual serines reveals that Serine 612
      is a critical residue in regulation of CTCF by CK2.

PMID- 15733853
TI  - The fidelity of DNA synthesis by human immunodeficiency virus type 1 reverse
      transcriptase increases in the presence of polyamines.
AB  - The high error rates characteristic of human immunodeficiency virus type-1
      reverse transcriptase (HIV-1 RT) are a presumptive source of the viral
      hypervariability that substantially affect viral pathogenesis and resistance to
      drug therapy. We have analyzed the potential role of polyamines in the fidelity
      of DNA synthesis by HIV-1 RT. The current study suggest that polyamines tested
      has the potential to be "antimutator". The polyamines exert the ability to reduce
      the misincorporation and mispair extension with both RNA/DNA and DNA/DNA template
      primers in the following order: spermine > spermidine > putrescine. In view of
      the significance of mutations of HIV, the possible roles of polyamines in the
      accuracy of DNA synthesis could be of particular importance; polyamines may
      affect the mutation rate of the virus.

PMID- 15733854
TI  - Evolution of different oligomeric glycyl-tRNA synthetases.
AB  - There are two oligomeric types of glycyl-tRNA synthetases (GlyRSs) in genome, the
      alpha2beta2 tetramer and alpha2 dimer. Here, we showed that the anticodon-binding
      domains (ABDs) of dimeric and tetrameric GlyRSs are non-homologous, although
      their catalytic central domains (CCDs) are homologous. The dimeric GlyRS_ABD is
      fused to the C-terminal of CCD in alpha-subunit, but the tetrameric GlyRS_ABD is
      to the C-terminal in beta-subunit during evolution. Generally, one species only
      contains one oligomeric type of GlyRS, but the both oligomeric GlyRSs with the
      multiple homologous domains can be observed in Magnetospirillum magnetotacticum
      genome, nevertheless, these homologous domains are probably from different
      genomes.

PMID- 15733856
TI  - Site-specific pseudophosphorylation modulates the rate of tau filament
      dissociation.
AB  - Hyperphosphorylation of tau is of fundamental importance for neurofibrillary
      lesion development in Alzheimer's disease, but the mechanisms through which it
      acts are not clear. Experiments with pseudophosphorylation mutants of full-length
      tau protein indicate that incorporation of negative charge into specific sites
      can modulate the aggregation reaction, and that this occurs by altering the
      critical concentration of assembly. Here, the kinetic origin of this effect was
      determined using quantitative electron microscopy methods and
      pseudophosphorylation mutant T212E in a full-length four-repeat tau background.
      On the basis of disaggregation rates, decreases in critical concentration
      resulted primarily from decreases in the dissociation rate constant. The results
      suggest a mechanism through which site-specific posttranslational modifications
      can modulate filament accumulation at low free intracellular tau concentrations.

PMID- 15733855
TI  - Free fatty acids increase PGC-1alpha expression in isolated rat islets.
AB  - PGC-1alpha mRNA and protein are elevated in islets from multiple animal models of
      diabetes. Overexpression of PGC-1alpha impairs glucose-stimulated insulin
      secretion (GSIS). However, it is not well known which metabolic events lead to
      upregulation of PGC-1alpha in the beta-cells under pathophysiological condition.
      In present study, we have investigated effects of chronic hyperlipidemia and
      hyperglycemia on PGC-1alpha mRNA expression in isolated rat islets. Isolated rat
      islets are chronically incubated with 0, 0.2 and 0.4 mM oleic acid/palmitic acid
      (free fatty acids, FFA) or 5.5 and 25 mM glucose for 72 h. FFA dose-dependently
      increases PGC-1alpha mRNA expression level in isolated islets. FFA also increases
      PGC-1alpha expression in mouse beta-cell-derived beta TC3 cell line. In contrast,
      25 mM glucose decreases expression level of PGC-1alpha. Inhibition of PGC-1alpha
      by siRNA improves FFA-induced impairment of GSIS in islets. These data suggest
      that hyperlipidemia and hyperglycemia regulate PGC-1alpha expression in islets
      differently, and elevated PGC-1alpha by FFA plays an important role in chronic
      hyperlipidemia-induced beta-cell dysfunction.

PMID- 15733858
TI  - Fractal nature of chromatin organization in interphase chicken erythrocyte
      nuclei: DNA structure exhibits biphasic fractal properties.
AB  - Arrangement of chromatin in intact chicken erythrocyte nuclei was investigated by
      small angle neutron scattering. The scattering spectra have revealed that on the
      scales between 15 nm and 1.5 microm the interior of the nucleus exhibited
      properties of a mass fractal. The fractal dimension of the protein component of
      cell nucleus held constant at approximately 2.5, while the DNA organization was
      biphasic, with the fractal dimension slightly higher than 2 on the scales smaller
      than 300 nm and approaching 3 on the larger scales.

PMID- 15733857
TI  - A newly synthetic chromium complex--chromium(phenylalanine)3 improves insulin
      responsiveness and reduces whole body glucose tolerance.
AB  - Low-molecular-weight organic chromium complexes such as chromium picolinate are
      often used as dietary supplements to improve insulin sensitivity and to correct
      dyslipidemia. However, toxicity associated with such chromium compounds has
      compromised their therapeutic value. The aim of this study was to evaluate the
      impact of a newly synthesized complex of chromium with phenylalanine, Cr(pa)3 on
      insulin-signaling and glucose tolerance. Cr(pa)3 was synthesized by chelating
      chromium(III) with D-phenylalanine ligand in aqueous solution. In mouse 3T3
      adipocytes, Cr(pa)3 augmented insulin-stimulated glucose-uptake as assessed by a
      radioactive-glucose uptake assay. At the molecular level, Cr(pa)3 enhanced
      insulin-stimulated phosphorylation of Akt in a time- and concentration-dependent
      manner without altering the phosphorylation of insulin receptor. Oral treatment
      with Cr(pa)3 (150 microg/kg/d, for six weeks) in ob/ob+/+ obese mice
      significantly alleviated glucose tolerance compared with untreated obese mice.
      Unlike chromium picolinate, Cr(pa)3 does not cleave DNA under physiological
      reducing conditions. Collectively, these data suggest that Cr(pa)3 may represent
      a novel, less-toxic chromium supplement with potential therapeutic value to
      improve insulin sensitivity and glycemic control in type II diabetes.

PMID- 15733859
TI  - The flexible loop of Bcl-2 is required for molecular interaction with
      immunosuppressant FK-506 binding protein 38 (FKBP38).
AB  - Bcl-2 contains an unusually long loop between the first and the second helices.
      This loop has been shown to be highly flexible based on NMR and X-ray
      crystallographic analyses of this region. Bcl-2 is regulated at the
      posttranslational level through phosphorylation of specific residues within the
      flexible loop. The biological role and posttranslational modifications of the
      loop of Bcl-2 is currently unclear. FK-506 binding protein 38 (FKBP38) has been
      reported to interact with Bcl-2, suggesting that FKBP38 could act as a docking
      molecule to localize Bcl-2 at the mitochondrial membrane [Shirane, M. and
      Nakayama, K.I. (2003) Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to
      mitochondria and inhibits apoptosis. Nat. Cell Biol. 5, 28-37]. Here, we
      investigated the molecular interaction between FKBP38 and Bcl-2, and demonstrated
      that Bcl-2 interacts with FKBP38 through the unstructured loop, and the
      interaction appears to regulate phosphorylation in the loop of Bcl-2.

PMID- 15733860
TI  - Cell death induced by Pteris semipinnata L. is associated with p53 and oxidant
      stress in gastric cancer cells.
AB  - In this study, we demonstrated that Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic
      acid (5F) had stronger cytotoxicity against MKN-45, a gastric cancer cell line
      bearing wild-type p53 than MKN-28, another gastric cancer cell line containing
      missense mutation in p53. The rapid increase of ROS level was involved in the
      mechanism of cytotoxicity. Classical features of apoptosis induced by 5F were
      observed in MKN-45 cells only or more significant in MKN-45 cells than MKN-28
      cells. Translocation of Bax from cytosol to mitochondria, reduction of delta psi
      m and DNA fragmentation were induced by 5F in the p53-dependent manner. We
      conclude that the expression of Bax and its downstream molecules requires the
      presentation of a wild-type p53 in the cells treated by 5F.

PMID- 15733861
TI  - Cell-cycle-dependent regulation of the human and mouse Tome-1 promoters.
AB  - Tome-1, which refers to a trigger of mitotic entry 1, mediates the destruction of
      the mitosis-inhibitory kinase, Wee1, via the E3 ligase, SCF. In turn, Tome-1
      itself is targeted for degradation by APC in the G1 phase of the cell cycle. In
      the present study, we analyzed the human and mouse Tome-1 promoter regions. Using
      synchronized cultures of NIH3T3 cells transfected with Tome-1 promoter/luciferase
      constructs, we showed that the promoter activity of Tome-1 is activated at the
      G2/M phase. Using various Tome-1 promoter/luciferase constructs, we showed that
      the CCAAT box located upstream of the transcription initiation site is important
      for the basal promoter activity. We identified a repressor element (cell-cycle
      dependent element/cell cycle gene homology region) in the vicinity of the
      transcription start site, and mutations within this element diminished the cell
      cycle-dependent transcriptional regulation of Tome-1.

PMID- 15733862
TI  - A part of ice nucleation protein exhibits the ice-binding ability.
AB  - We generated a recombinant 96-residue polypeptide corresponding to a sequence
      Tyr176-Gly273 of ice nucleation protein from Pseudomonas syringae (denoted
      INP96). INP96 exhibited an ability to shape an ice crystal, whose morphology is
      highly similar to the hexagonal-bipyramid generally identified for antifreeze
      protein. INP96 also showed a non-linear, concentration-dependent retardation of
      ice growth. Additionally, circular dichroism and NMR measurements suggested a
      local structural construction in INP96, which undergoes irreversible thermal
      denaturation. These data imply that a part of INP constructs a unique structure
      so as to interact with the ice crystal surfaces.

PMID- 15733863
TI  - Inducible double-stranded RNA expression activates reversible transcript turnover
      and stable translational suppression of a target gene in transgenic tobacco.
AB  - A binary vector amenable to high-throughput cloning was constructed for ethanol
      inducible expression of double-stranded RNA (dsRNA) in plants. Silencing of a
      transgene encoding beta-glucuronidase (GUS) was then examined at RNA and protein
      levels in tobacco. Transient gene silencing could be effectively achieved in
      plants with higher expression levels of alcR (the ethanol sensor) after single
      application of 1% ethanol (v/v) through root drenching. GUS activities showed
      more dramatic pattern of loss and recovery in young leaves than in older leaves.
      Repeated ethanol treatment resulted in extended gene suppression and increased
      loss of GUS activities. Interestingly, recovery of GUS transcript level is
      dramatically earlier than that of GUS protein levels as measured by enzyme
      assays. These observations indicate that dsRNA-mediated gene silencing may occur
      through more stable translational inhibition in addition to reversible targeted
      RNA degradation.

PMID- 15733864
TI  - Fibrillogenesis of apomyoglobin facilitated by aggregation sequence of yeast
      Sup35 in various regions.
AB  - To examine the effect of aggregation sequence QGGYQQQYNP from yeast Sup35 on
      fibril formation of sperm whale apomyoglobin (apoMb), we constructed several
      mutants via substitution. Urea-induced unfolding of apoMb confirms that the
      substitution of the aggregation sequence does not significantly affect the
      stability of the mutants compared to wild type (WT) at pH 4.2. Under this
      condition, however, despite the difference in rate most apoMb mutants form
      fibrils more readily than WT with distinct morphology. These results suggest that
      the aggregation sequence facilitates fibril assembly of apoMb at acidic pH in
      vitro and this facilitation depends on the regions replaced.

PMID- 15733865
TI  - SHARP-2/Stra13/DEC1 as a potential repressor of phosphoenolpyruvate carboxykinase
      gene expression.
AB  - The influence of the enhancer of split- and hairy-related protein-2 (SHARP-2)
      transcriptional repressor on the expression of rat phosphoenolpyruvate
      carboxykinase (PEPCK) gene was examined. When H4IIE cells were treated with
      epigallocatechin gallate, a green tea constituent, an increase in SHARP-2 mRNA
      levels and a decrease in PEPCK mRNA levels were observed. The adenovirus-mediated
      overexpression of SHARP-2 in H4IIE cells and primary cultured rat hepatocytes led
      to a decrease in the levels of PEPCK mRNA. Finally, when a SHARP-2 expression
      plasmid was transiently transfected with various reporter plasmids into MH1C1
      cells, the promoter activity of a PEPCK reporter plasmid was specifically
      decreased. Based on these findings, we conclude that SHARP-2 is a potential
      repressor of PEPCK gene expression.

PMID- 15733866
TI  - Heavy metal transport by AtHMA4 involves the N-terminal degenerated metal binding
      domain and the C-terminal His11 stretch.
AB  - The Arabidopsis thaliana AtHMA4 is a P1B-type ATPase that clusters with the
      Zn/Cd/Pb/Co subgroup. It has been previously shown, by heterologous expression
      and the study of AtHMA4 knockout or overexpressing lines in Arabidopsis , that
      AtHMA4 is implicated in zinc homeostasis and cadmium tolerance. Here, we report
      the study of the heterologous expression of AtHMA4 in the yeast Saccharomyces
      cerevisiae. AtHMA4 expression resulted in an increased tolerance to Zn, Cd and Pb
      and to a phenotypic complementation of hypersensitive mutants. In contrast, an
      increased sensitivity towards Co was observed. An AtHMA4::GFP fusion protein was
      observed in endocytic vesicles and at the yeast plasma membrane. Mutagenesis of
      the cysteine and glutamate residues from the N-ter degenerated heavy metal
      binding domain impaired the function of AtHMA4. It was also the case when the C
      ter His11 stretch was deleted, giving evidence that these amino acids are
      essential for the AtHMA4 binding/translocation of metals.

PMID- 15733867
TI  - Histone deacetylase inhibitor BL1521 induces a G1-phase arrest in neuroblastoma
      cells through altered expression of cell cycle proteins.
AB  - Histone deacetylase inhibitors (HDACi) have been discovered as potential drugs
      for cancer treatment. The effect of BL1521, a novel HDACi, on the cell cycle
      distribution and the induction of apoptosis was investigated in a panel of MYCN
      single copy and MYCN amplified neuroblastoma cell lines. BL1521 arrested
      neuroblastoma cells in the G1 phase and induced up to 30% apoptosis.
      Downregulation of CDK4, upregulation of p21(WAF1/CIP1) and an increase of
      hypophosphorylated retinoblastoma protein were observed, indicating a possible
      mechanism for the cell-cycle arrest. BL1521 also induced downregulation of p27,
      which may underlie the observed induction of apoptosis.

PMID- 15733868
TI  - Human receptor Smoothened, a mediator of Hedgehog signalling, expressed in its
      native conformation in yeast.
AB  - Though the role of Hedgehog (Hh) signalling in patterning and differentiation
      during development is well established, the underlying signal transduction
      mechanisms remain obscure. This is the first report on the overexpression of the
      human Hh signalling receptor Smoothened (hSmo) in Saccharomyces cerevisiae and
      Pichia pastoris. We show that hSmo is expressed in both types of yeast in its
      native conformational state. The first purification presented here will allow the
      characterisation of hSmo expressed in yeast, and the scale-up of hSmo production
      enabling structural studies to develop new therapeutic approaches against tumors
      and neurodegenerative diseases induced by Hh signalling dysfunction.

PMID- 15733869
TI  - Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP response
      element binding protein, CREB.
AB  - To maintain homeostasis, cells often respond to stressful extra-cellular stimuli
      by new gene expression. Serum/glucocorticoid-induced kinase (SGK) is an immediate
      early gene whose expression is induced by a variety of extra-cellular stimuli.
      Here, we examine the possibility that SGK can directly phosphorylate the
      transcription factor cyclic AMP response element binding protein (CREB). In a
      cell-free context, SGK physically associates with CREB and SGK phosphorylates it
      on serine 133. Phospho-serine 133 is essential for stimulating the
      transcriptional activity of CREB. Further, we show that in a variety of cellular
      contexts, SGK phosphorylates CREB. Activation of receptor tyrosine kinase
      pathways or the phosphoinositide-dependent kinase 1 (PDK1) lead to SGK-dependent
      CREB phosphorylation. Hormonal stimulation of epithelial cells leads to the
      induction of endogenous SGK and CREB phosphorylation. A dominant-negative form of
      SGK blocks dexamethasone-induced CREB phosphorylation. Our studies indicate that
      stimulation of SGK can lead to CREB phosphorylation, suggesting that CREB
      dependent gene transcription is an important link between stressful extra
      cellular signals and cellular responses.

PMID- 15733870
TI  - Persistent TNF-alpha exposure impairs store operated calcium influx in CD4+ T
      lymphocytes.
AB  - Persistent tumour necrosis factor alpha (TNF-alpha) exposure uncouples proximal T
      cell receptor (TCR)-signalling events. Here, we demonstrate that chronic TNF
      alpha exposure also attenuates signalling distal to the TCR, by specifically
      inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T-cells. Mitogen-induced
      Ca2+ responses were impaired in a dose dependent manner, and TCR-induced Ca2+
      responses were also significantly reduced. The impairment of Ca2+ influx strongly
      correlated with poor function as proliferative responses to both mitogen and anti
      CD3/CD28 stimulation were suppressed. Our findings show that persistent TNF-alpha
      exposure of T-cells specifically inhibits store operated Ca2+ influx. This may
      affect gene activation and contribute to the poor T-cell function in chronic
      inflammatory disease.

PMID- 15733871
TI  - WRKY group IId transcription factors interact with calmodulin.
AB  - Calmodulin (CaM) is a ubiquitous Ca(2+)-binding protein known to regulate diverse
      cellular functions by modulating the activity of various target proteins. We
      isolated a cDNA encoding AtWRKY7, a novel CaM-binding transcription factor, from
      an Arabidopsis expression library with horseradish peroxidase-conjugated CaM. CaM
      binds specifically to the Ca(2+)-dependent CaM-binding domain (CaMBD) of AtWRKY7,
      as shown by site-directed mutagenesis, a gel mobility shift assay, a split
      ubiquitin assay, and a competition assay using a Ca2+/CaM-dependent enzyme.
      Furthermore, we show that the CaMBD of AtWRKY7 is a conserved structural motif (C
      motif) found in group IId of the WRKY protein family.

PMID- 15733872
TI  - Lysosome destabilization by cytosolic extracts, putative involvement of
      Ca(2+)/phospholipase C.
AB  - Lysosomal disintegration is a crucial event for living cells, but mechanisms for
      the event are still unclear. In this study, we established that the cytosolic
      extracts could enhance lysosomal osmotic sensitivity and osmotically destabilize
      the lysosomes. The cytosol also caused the lysosomes to become more swollen in
      the hypotonic sucrose medium. The results indicate that the cytosol induced an
      osmotic shock to the lysosomes and an influx of water into the organelle. Since
      the effects of cytosol on the lysosomes could be abolished by O
      tricyclo[5.2.1.0(2,6)]dec-9-yl dithiocarbonate potassium salt (D609), a specific
      inhibitor of cytosolic phospholipase C (PLC), the PLC might play an important
      role in the lysosomal osmotic destabilization. The activity of cytosolic PLC and
      the extent of enzyme latency loss of the cytosol-treated lysosomes exhibited a
      similar biphasic dependence on the cytosolic Ca2+ concentration. In addition, the
      cytosol did not osmotically destabilize the lysosomes until the cytosolic calcium
      ions rose above 100 nM. It suggests that the destabilization effect of cytosol on
      the lysosomes is Ca(2+)-dependent.

PMID- 15733873
TI  - Arabidopsis ADC genes involved in polyamine biosynthesis are essential for seed
      development.
AB  - Arginine decarboxylase (ADC) is a rate-limiting enzyme that catalyzes the first
      step of polyamine (PA) biosynthesis in Arabidopsis thaliana. We generated a
      double mutant deficient in Arabidopsis two ADC genes (ADC1-/- ADC2-/-) and
      examined their roles in seed development. None of the F2 seedlings from crosses
      of adc1-1 and adc2-2 had the ADC1-/- ADC2-/- genotype. In addition, some abnormal
      seeds were observed among the ADC1+/- ADC2-/- and ADC1-/- ADC2+/- siliques.
      Viable offspring with the ADC1-/- ADC2-/- genotype could not be obtained from the
      ADC1+/- ADC2-/- and ADC1-/- ADC2+/- plants. These results indicate that AtADC
      genes are required for production of polyamines that are essential for normal
      seed development in Arabidopsis.

PMID- 15733875
TI  - Oral misoprostol versus intracervical dinoprostone for induction of labor.
AB  - OBJECTIVES: To compare oral misoprostol with dinoprostone for induction of labor
      and their effects on the fetal heart rate patterns. METHODS: In a randomized
      controlled trial, 200 patients received either misoprostol 50 mug orally for
      every 4 h, or dinoprostone 0.5 mg intracervically for every 6 h.
      Cardiotocographic recordings, in 10-min windows 30, 60, and 80 min after
      prostaglandin administration during induction and continuously during labor, were
      compared between the two groups. Primary outcome for effectiveness and safety was
      assessed in terms of the number of vaginal deliveries within 24 h and fetal heart
      rate abnormalities during induction and labor respectively. RESULTS: Data from 96
      patients in the misoprostol group and 95 in the dinoprostone group were analyzed.
      There were no significant differences in respect of the number of vaginal
      deliveries within 24 h (RR 1.12; 95% CI 0.88-1.42). The frequency of suspicious
      and pathological fetal heart rate patterns did not differ significantly but
      significantly more cardiotocographs in the dinoprostone group had non-reassuring
      baseline variability 60 min after dose administration (RR 0.33; 95% CI 0.14
      0.77). Maternal and neonatal outcomes did not differ significantly. CONCLUSION:
      Oral misoprostol is as effective as intracervical dinoprostone for induction of
      labor with no difference in the frequency of fetal heart rate abnormalities.

PMID- 15733876
TI  - Soft forceps.
AB  - OBJECTIVE: The risk of maternal and fetal trauma and, chiefly, the fear of law
      suits, have contributed to a significant decline in rates of forceps-assisted
      deliveries and an increase in rates of cesarean sections, especially in the
      United States. Our experience with gas-sterilized forceps blades covered with a
      soft rubber coating--the "soft" forceps--is described. METHOD: Ninety-six women
      who required a forceps-assisted delivery for standard indications were randomly
      allocated to 2 groups. There were 51 women in the regular forceps group and 45
      women in the soft forceps group. Low forceps delivery with a Simpson instrument
      was used in all cases. The groups were compared for fetal injury. RESULTS: The
      rates of severe facial abrasion and minimal marking were 4.1% and 61%,
      respectively, in the regular forceps group and 1.9% and 34% in the soft forceps
      group. CONCLUSION: The soft forceps may reduce the rates of neonatal facial
      abrasion and skin bruises. The forceps should be further perfected, as well as
      vacuum extractors; they should both continue to be part of the obstetrician's
      armamentarium.

PMID- 15733877
TI  - Re-laparotomy after Cesarean section.
AB  - OBJECTIVE: The objective of the study was to find out the indications for
      management and the outcomes of reopening the abdomen during the puerperium after
      Cesarean section. PATIENTS AND METHODS: This was a retrospective descriptive
      survey at the Korle Bu Teaching Hospital in Accra, Ghana. RESULTS: There were
      6120 Cesarean sections (17%) out of a total of 36,010 deliveries. Re-laparotomy
      was done in 44 patients (0.7%) of the Cesarean sections. The indications were:
      hemorrhage from uterine atony, hemorrhage from placental bed after operation for
      placenta previa, uterine sepsis with hemorrhage, hemorrhage after Cesarean
      section, myomectomy and hemorrhage from anterior abdominal wound dehiscence. The
      main surgeries performed were: hysterectomy, ligation of ascending branches of
      uterine arteries, ligation of hypogastric arteries, debridement and re-suturing
      of the uterine incision and secondary suturing of anterior abdominal wall. There
      were 6 near missed fatalities. There were 4 mortalities caused by excessive
      hemorrhage and severe sepsis. CONCLUSION: The case fatality rate for re
      laparotomy after Cesarean section is high (9%). Near missed-fatalities are
      common. To reduce the unfavorable outcomes, instituting more intensive education
      on the use of the partograph should prevent prolonged labor. Centers carrying out
      Cesarean section should have efficient blood transfusion service in place.

PMID- 15733878
TI  - Hyaluronidase versus Foley catheter for cervical ripening in high-risk term and
      post term pregnancies.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of Foley catheter and
      hyaluronidase for cervical ripening. METHOD: Randomized controlled trial where
      140 pregnant women, with gestational age > or = 37 weeks, indication for labor
      induction and an unripe cervix, were enrolled, allocated in two groups according
      to the method of cervical ripening before labor induction. Statistical analysis
      used Student's t-test, Mann-Whitney, Chi-square test, survival analysis, risk
      ratios and number needed to treat. RESULTS: Time of induction, dose of oxytocin
      and mode of delivery had better results in the Foley catheter group. Comfort with
      the method was higher in the hyaluronidase group. CONCLUSIONS: Both methods were
      effective and safe for cervical ripening. The Foley catheter group experienced a
      shorter period of induction, required a lower dose of oxytocin and had higher
      vaginal delivery rates, while the women who used hyaluronidase declared greater
      comfort with the method.

PMID- 15733879
TI  - Genetic thrombophilias and uterine artery Doppler velocimetry and preeclampsia.
AB  - OBJECTIVE: The aim of this study was to evaluate the correlation between genetic
      thrombophilic mutations, uterine artery Doppler at 24 weeks of gestation and
      preeclampsia. METHODS: In a case control study we performed the genetic analysis
      for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin
      gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase
      (MTHFR) gene in 103 women that had already attended routine ultrasonography
      scanner at 20 weeks at our Department. RESULTS: The frequency of heterozygous
      carriers of the factor V Leiden was 17.4% in the women with preeclampsia and
      abnormal artery Doppler compared with 3.12% in the patients with normal
      pregnancies. This difference was statistically significant (P<0.05). The
      frequency of mutation G20210A of prothrombin gene was 1.5 vs. 4.3% between women
      with normal pregnancies and with preeclampsia. This difference is not
      statistically significant. The frequency of homozygous patients for the C677T
      mutation of MTHFR gene among the patients with preeclampsia was 21.7% and in the
      control group was 10.3%, but this difference is not statistically significant. No
      thrombophilic gene variants were found in women with preeclampsia and normal
      uterine artery Doppler. CONCLUSION: We demonstrated the important association
      between factor V Leiden mutation, abnormal uterine Doppler at 24 weeks and
      preeclampsia in our population.

PMID- 15733880
TI  - The effect of exercise on the intensity of low back pain in pregnant women.
AB  - OBJECTIVE: To investigate the effect of exercise during pregnancy on the
      intensity of low back pain and kinematics of spine. METHOD: A prospective
      randomized study was designed. 107 women participated in an exercise program
      three times a week during second half of pregnancy for 12 weeks and 105 as
      control group. All filled a questionnaire between 17-22 weeks of gestation and 12
      weeks later for assessment of their back pain intensity. Lordosis and flexibility
      of spine were measured by Flexible ruler and Side bending test, respectively, at
      the same times. Weight gain during pregnancy, Pregnancy length and neonatal
      weight were recorded. RESULT: Low back pain intensity was increased in the
      control group. The exercise group showed significant reduction in the intensity
      of low back pain after exercise (p<0.0001). Flexibility of spine decreased more
      in the exercise group (p<0.0001). Weight gain during pregnancy, pregnancy length
      and neonatal weight were not different between the two groups. CONCLUSION:
      Exercise during second half of the pregnancy significantly reduced the intensity
      of low back pain, had no detectable effect on lordosis and had significant effect
      on flexibility of spine.

PMID- 15733881
TI  - Mode of delivery and pelvic floor muscle strength and sexual function after
      childbirth.
AB  - OBJECTIVE: To investigate the respective roles of the mode of delivery and
      strength of pelvic floor muscles in the sexual function of women. METHOD: Thirty
      two women who were delivered vaginally and 21 women who underwent cesarean
      delivery at the Celal Bayar University School of Medicine Obstetrics Department
      were enrolled in the study, and 15 nulliparas were recruited as controls. Sexual
      function was assessed in all women by a validated questionnaire (the Female
      Sexual Function Index). Desire, arousal, lubrication, orgasm, satisfaction, and
      pain were measured separately, and pelvic floor muscle strength was assessed by a
      perineometer. Sexual function was compared among the 3 groups. The correlation
      between pelvic floor muscle strength and sexual function was also investigated.
      RESULTS: Pelvic floor muscle strength was significantly lower in the group
      vaginally delivered compared with the group delivered by cesarean section and the
      nulliparous group (P<0.05). There was no difference between the groups regarding
      sexual function (P>0.05), and there was also no correlation between sexual
      function and pelvic muscle strength. CONCLUSION: Pelvic floor muscle strength and
      mode of delivery did not affect sexual function in our study participants. The
      muscular component of female sexual function should be further investigated.

PMID- 15733882
TI  - Low-dose secnidazole in the treatment of bacterial vaginosis.
AB  - OBJECTIVE: To determine whether bacterial vaginosis could be cured with a single
      1-g oral dose of secnidazole. MATERIAL AND METHODS: A total of 80 women were
      recruited at the outpatient gynecologic clinic of Manuel Noriega Hospital,
      Maracaibo, Venezuela. Diagnosis and patient enrollment were based on the Amsel
      criteria. The participants were randomized to 2 groups. In group 1 (n=44)
      participants received a single 1-g oral dose and in group 2 (n=32) participants
      received a single 2-g oral dose of secnidazole. Clinical cure was defined as the
      absence of the characteristic symptoms (a bad odor and a grossly abnormal
      discharge) and at least 2 of the following: vaginal pH less than 4.5, no fish
      odor on addition of KOH, and no Gardnerella vaginalis or clue cells on wet-mount
      examination. Cytologic cure was defined as an absence of G. vaginalis on a
      Papanicolaou (Pap) smear. RESULTS: Clinical cure was experienced by 95.5% of the
      women who received the 1-g oral dose and by 97.4% of the women who received the 2
      g oral dose of secnidazole. There was no significant difference between the
      groups in the clinical resolution of bacterial vaginosis. Following treatment,
      results were negative for G. vaginalis in 94.7% of the women. In group 1, 41
      women (93.2%), and in group 2, 31 women (96.9%) had cytologic cure. The Pap smear
      revealed G. vaginalis in 3 of the women in group 1 and 1 of the women in group 2
      (P=0.47). Twenty-seven women (35.5%) reported mild side effects. More women had
      adverse effects in group 1 (n=16) than in group 2 (n=11) but this difference was
      not statistically significant. CONCLUSION: This clinical study showed that a
      single 1-g oral dose of secnidazole is effective to cure bacterial vaginosis
      associated with G. vaginalis.

PMID- 15733883
TI  - Prognostic significance of DNA quantification by flow cytometry in ovarian
      tumors.
AB  - OBJECTIVE: The objective of our study is to evaluate prognostic significance of
      DNA quantification by flow cytometry in ovarian tumor. METHODS: A prospective
      analysis was performed on 56 ovarian tumor patients treated in the Yonsei Medical
      Center from Feb. 2000 to Jan. 2003. RESULTS: Regarding the association between
      tumor grade and the DNA quantitative analysis, as tumor grade increased, the
      quantity of aneuploid cells and S-phase fraction (SPF) increased. In addition,
      SPF was increased significantly in the advanced staged patients (P=0.04) and SPF
      was significantly increased in aneuploid tumors (P=0.03). The overall survival
      rate was poor for patients with aneuploid tumors and for patients with tumors
      showing over SPF (10%). CONCLUSION: Our data demonstrated that the prognosis was
      poor for patients with aneuploid cancers or increased SPF. Therefore, DNA
      quantification by flow cytometry may provide important information for predicting
      the prognosis of the disease.

PMID- 15733884
TI  - Serum tumor necrosis factor alpha receptors p55/p75 ratio and ovarian cancer
      detection.
AB  - OBJECTIVE: Early ovarian cancer detection is still very difficult and patients
      are mostly in advanced stages, with obvious influence on poor prognosis. METHOD:
      Fifty-one ovarian cancer patients and 16 healthy controls had the serum
      concentrations of TNF alpha receptor p55, p75 and CA-125 measured prospectively
      and preoperatively. RESULT: Mean concentrations of TNF alpha receptor p55, p75
      and CA-125 in patients with ovarian cancer were higher than in controls. The
      ratios of p55 and p75 receptor in ovarian cancer and controls were 0.73+/-0.38
      and 0.55+/-0.06 respectively. The areas under ROC curve in detecting malignancy
      (all FIGO stages) were 0.73, 0.65, 0.88 and 0.85 for p55, p75, p55/p75 ratio and
      CA-125 respectively. The areas under ROC curve in detecting stage I of ovarian
      cancer were 0.52, 0.60, 0.84 and 0.66 for p55, p75, p55/p75 ratio and CA-125
      respectively. CONCLUSION: Serum TNF alpha p55/p75 ratio showed promising value in
      ovarian cancer detection.

PMID- 15733885
TI  - Successful treatment of cervical aplasia using a peritoneal graft.
AB  - OBJECTIVE: To evaluate the efficacy of a peritoneal graft for the treatment of
      cervical aplasia. METHOD: Four patients with cervical aplasia who had a
      functioning endometrium and hematometra were recruited for this clinical trial.
      Through an abdominoperineal approach a plastic stent was inserted between the
      endometrial cavity and the upper part of the vagina; then, a graft of peritoneum
      was applied over the stent. In the absence of a vagina, grafts of skin or
      amniotic membrane were also used. The plastic stent was removed after 1 month in
      2 patients and after 1 week in the 2 other patients. RESULT: After more than 1
      year of observation the 4 patients had regular menstrual cycles with normal
      menstruation. Sonographic examinations also showed empty uterine cavities.
      CONCLUSION: Traditional gynecology textbooks recommend hysterectomy in cases of
      cervical aplasia. This report presents a new technique with 2 variations using a
      peritoneal graft. Although both variations were successful in the treatment of
      cervical aplasia in 4 women, more trials are needed to determine which one should
      be developed.

PMID- 15733886
TI  - The HDL2/HDL3 ratio in menopause.
AB  - OBJECTIVES: The influence of the menopause on the HDL2/HDL3 ratio was assessed in
      association with hypertriglyceridemia. METHODS: Fasting blood samples were
      collected from 607 patients. Commercially available enzymatic methods were used
      for determination of TG, and total HDL-C. HDL2 and HDL3 were measured by
      ultracentrifugation. RESULTS: The HDL2/HDL3 ratio had a strong negative
      correlation with TG (r=-0.272, P<0.0001 and r=-0.314, P<0.0001) in both pre- and
      postmenopausal women. No significant differences were observed in HDL2, HDL3, and
      HDL2/HDL3 ratio between pre- and postmenopausal women without
      hypertriglyceridemia. Postmenopausal women had a significantly higher HDL2/HDL3
      ratio than premenopausal women with hypertriglyceridemia. CONCLUSIONS: These
      results indicate that menopausal status not only increases plasma LDL-cholesterol
      and triglyceride levels, but also increases the HDL2/HDL3 ratio when associated
      with elevation of plasma triglyceride levels. These changes may increase the risk
      for CHD due to enlargement of the lipid pool.

PMID- 15733888
TI  - Pregnancy outcome in women with echogenic amniotic fluid at term gestation.

PMID- 15733887
TI  - Tubal patency after clinical treatment of unruptured ectopic pregnancy.
AB  - OBJECTIVE: To evaluate tubal patency using hysterosalpingography after clinical
      treatment of tubal pregnancy. METHOD: Of 80 patients who underwent
      hysterosalpingography after clinical treatment of tubal pregnancy from April 1994
      to February 2002, 30 were treated with a single 50 mg/m(2) dose of methotrexate
      intramuscularly (n=30) and 50 were followed up expectantly. RESULTS: Patency of
      the ipsilateral tube was 84% after methotrexate treatment and 78% after expectant
      management. In addition, contralateral tubal patency was 97% after methotrexate
      treatment and 92% after expectant management. There were no statistically
      significant differences between the groups. CONCLUSION: Findings from this study
      suggest similar tubal patency rates after methotrexate treatment and expectant
      management.

PMID- 15733889
TI  - Rupture of noncommunicating rudimentary uterine horn at 27 weeks' gestation with
      neonatal and maternal survival.

PMID- 15733890
TI  - Transabdominal cervicoisthmic cerclage.

PMID- 15733891
TI  - Maternal mortality in rural Nigeria.

PMID- 15733892
TI  - Bone turnover in preeclamptic and normotensive pregnancy.

PMID- 15733893
TI  - Giant myomas of the uterus.

PMID- 15733894
TI  - Misoprostol as an adjunctive medication in late surgical abortion.

PMID- 15733895
TI  - Pelvic inflammatory disease with perforated peptic ulcer mimicking tubo-ovarian
      abscess.

PMID- 15733896
TI  - Non-puerperal uterine rupture after use of misoprostol and a Foley catheter for
      management of uterine bleeding.

PMID- 15733897
TI  - CA 125 half-life breakpoint between a "good" and "poor" prognosis in patients
      with ovarian cancer.

PMID- 15733899
TI  - Peri-hepatic endometriosis.

PMID- 15733898
TI  - Inhibin B, activin A, and follistatin and the pathogenesis of polycystic ovary
      syndrome.

PMID- 15733900
TI  - The management of abnormal cervical smears by Nigerian gynecologists.

PMID- 15733901
TI  - Ethnic background and in vitro fertilization outcomes.
AB  - OBJECTIVE: To compare IVF outcomes among women of different ethnic backgrounds.
      METHOD: This was a retrospective cohort study. Between August 1994 and March
      1998, the first IVF cycles of 1039 white, 43 African American, 18 Hispanic, and
      35 Asian women were examined. RESULT: Ages and day 3 FSH levels did not differ
      significantly among patients. African Americans weighed more than other ethnic
      groups and were also more likely to have tubal factor infertility than whites.
      IVF cycle characteristics did not vary among the ethnic groups with the exception
      that African Americans had a higher level of estradiol on day of HCG than whites.
      Pregnancy outcomes did not differ among the ethnic groups. The percentage of
      ectopic pregnancies, spontaneous abortions, and successful live births was
      similar among the groups. CONCLUSION: Our data showed no significant difference
      in pregnancy outcomes with IVF among the ethnic groups.

PMID- 15733902
TI  - A systematic review of large scale and heterogeneous gene array data in heart
      failure.
AB  - Microarray analysis has become a widely available tool for the generation of gene
      expression data on a genomic scale. Since the studies with similar protocols are
      growing, it has become necessary to systematically revise the large body of
      literature to decipher the gene expression data. In this review, we analyzed and
      critically discussed the database presented from 14 published studies that showed
      the gene expression profile in heart failure (HF) using microarray as a primary
      tool. After comparing the diverse database from these studies, we explain the
      protein translational, matri-cellular, immunological and fibrosis-related
      mechanisms in HF. In addition to previously annotated genes, we analyzed two
      differentially expressed expressed sequence tags (ESTs) (KIAA0152 and Suppressor
      of G(Two) allele of the suppressor of kinetochore protein-1, SGT1) in HF and
      showed how bio-informatic analysis of ESTs can lead to the identification of
      novel pathways active in HF. We have also discussed the new publicly accessible
      tools that link the gene expression data to gene ontogeny (GO) and functionality.
      Finally, we have systematically revised the chromosomal localization of the genes
      that are specifically up-regulated in HF. We have thus spotted chromosome 1, 2,
      11 and 12 as the chromosomal hotspots of HF. This methodical approach will
      simplify the existing concepts on the evolution and progression of HF and lead us
      toward the development of newer diagnostic and therapeutic tools. Although
      modeled to HF, this approach should be of broader scientific interest to
      elaborate multiple genes and complex pathways.

PMID- 15733903
TI  - Small heat shock proteins: a new classification scheme in mammals.
AB  - Small MW heat shock proteins (i.e. sHSPs approximately 15-30 kDa) share
      significant sequence similarity within the "alpha-crystallin domain" but exhibit
      different patterns of gene expression, transcriptional regulation, sub-cellular
      localization, and, perhaps, function. The chaperone-like properties of many sHSPs
      are defined biochemically by their ability to prevent protein aggregation and/or
      restore biological activity of client substrates in vitro. Furthermore, such
      functions are widely believed to mitigate protein misfolding and denaturation
      triggered by noxious environmental stimuli such as hyperthermia stress, decreased
      pH(i), osmotic stress, heavy metals, hypoxia, and ischemic injury in vivo. At
      least 10 mammalian sHSPs, several with tissue-restricted expression, have been
      identified in recent genome surveys of mice, rats, and humans, but their
      functions have remained poorly understood. Here, we propose a simple
      classification scheme for sHSPs to reflect emerging evidence that their
      specialized roles (e.g. apoptosis, protein trafficking, redox control, and
      cytoskeletal interactions) might be inextricable linked to both coordinate
      regulation and multimeric protein complexes in a lineage-specific manner. Thus,
      Class I proteins display ubiquitous expression, whereas the tissue distribution
      of Class II proteins is primarily restricted to myogenic and testicular lineages.
      Because the expression patterns and modifications of sHSPs are potentially
      surrogate biosignatures for underlying pathophysiological events, we propose that
      this classification should accelerate progress to define the functional
      diversification for sHSPs especially in selective tissues predisposed to
      inheritable, degenerative, and other acquired diseases in humans.

PMID- 15733904
TI  - Bcl-2 in endothelial cells is increased by vitamin E and alpha-lipoic acid
      supplementation but not exercise training.
AB  - Atherosclerotic plaque contains apoptotic endothelial cells with oxidative stress
      implicated in this process. Vitamin E and alpha-lipoic acid are a potent
      antioxidant combination with the potential to prevent endothelial apoptosis.
      Regular exercise is known to increase myocardial protection, however, little
      research has investigated the effects of exercise on the endothelium. The purpose
      of these studies was to investigate the effects of antioxidant supplementation
      and/or exercise training on proteins that regulate apoptosis in endothelial
      cells. Male rats received a control or antioxidant-supplemented diet (vitamin E
      and alpha-lipoic acid) and were assigned to sedentary or exercise-trained groups
      for 14 weeks. Left ventricular endothelial cells (LVECs) were isolated and levels
      of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax were
      measured. Antioxidant supplementation caused a fourfold increase in Bcl-2 (P <
      0.05) with no change in Bax (P > 0.05). Bcl-2:Bax was increased sixfold with
      antioxidant supplementation compared to non-supplemented animals (P < 0.05).
      Exercise training had no significant effect on Bcl-2, Bax or Bcl-2:Bax either
      alone or combined with antioxidant supplementation (P > 0.05) compared to non
      supplemented animals. However, Bax was significantly lower (P < 0.05) in the
      supplemented trained group compared to non-supplemented trained animals. Cultured
      bovine endothelial cells incubated for 24 h with vitamin E and/or alpha-lipoic
      acid showed the combination of the two antioxidants increased Bcl-2 to a greater
      extent than cells incubated with the vehicle alone. In summary, vitamin E and
      alpha-lipoic acid increase endothelial cell Bcl-2, which may provide increased
      protection against apoptosis.

PMID- 15733905
TI  - Pharmacological modulation of the hyperpolarization-activated current (I f) in
      human atrial myocytes: focus on G protein-coupled receptors.
AB  - AIMS: In human atrial myocytes (HuAM) two beta-adrenergic receptors (beta-AR) and
      four splicing-variants of the serotonin 5-HT(4) receptor are present. Multiple
      coupling with G stimulatory (G(s)) and G inhibitory (G(i)) proteins has been
      proposed for both beta(2)-AR and 5-HT((4b)) subtypes, but no functional data
      exist in HuAM. Serotonin (5-HT) and catecholamines are able to trigger
      arrhythmias in human atrium, but the underlying cellular mechanisms are not
      completely understood. The pacemaker current (I(f)) is an inward Na(+)/K(+)
      current, constitutively present in HuAM and directly modulated by cAMP; I(f)
      could play a role in triggering human atrial arrhythmias. This study evaluated
      the different G protein coupling of beta(1)-AR, beta(2)-AR and 5-HT(4) receptors
      by assessing the modulation of I(f) by selective stimuli. METHODS: HuAM were
      isolated from right atrial appendages and utilized for patch-clamp recording. The
      coupling of receptor subtypes with G(i) proteins was tested by incubating HuAM in
      pertussis toxin (PTX). RESULTS: Beta(1)-AR stimulation (Isoprenaline [ISO] + ICI
      118,551), and 5-HT caused a concentration-dependent significant shift of the half
      activation potential of I(f) activation curve (DeltaV(h)), P < 0.01. beta(2)-AR
      stimulation (ISO 1 microM + CGP 20712A) also significantly shifted V(h) (P <
      0.0001), but with DeltaV(h)[beta(2)-AR] significantly smaller than the effect
      caused by 1 microM beta(1)-AR stimulation (P < 0.05). Pre-treatment of HuAM with
      PTX did not alter the effect of beta(1)-AR stimulation (both 0.1 and 1 microM)
      and 1 microM 5-HT on I(f), but significantly increased the effect in response to
      beta(2)-AR stimulation and 0.1 microM 5-HT (P < 0.05 for both), thus suggesting a
      G(i) protein coupling of these receptors. CONCLUSIONS: Our results provide the
      first functional evidence of the different G protein coupling of beta(1)-AR,
      beta(2)-AR and 5-HT(4) receptors in HuAM. Further they support the view that I(f)
      current might play an important role in triggering catecholamines and serotonin
      induced atrial arrhythmias.

PMID- 15733906
TI  - Alterations in the heart mitochondrial proteome in a desmin null heart failure
      model.
AB  - Desmin, the major muscle-specific intermediate filament (IF) protein, is
      essential for mitochondrial behavior and function and maintenance of healthy
      muscle. Mice null for desmin develop dilated cardiomyopathy characterized by
      extensive cardiomyocyte death, fibrosis, calcification and eventual heart
      failure. We sought to investigate the heart mitochondrial proteome of wild type
      and desmin null mice in order to understand the cardiac and skeletal myopathy
      phenotype of desmin deficiency. The proteins were analyzed by 2-D
      electrophoresis, followed by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry. Three hundred and eighty different gene products were
      identified, about 50% of which were enzyme subunits. Cytoskeletal and muscle
      specific proteins, calcium-binding proteins, proteins with various other
      functions and about 70 unknown, hypothetical or poorly described gene products,
      were also identified. We have observed differences in most metabolic pathways, in
      apoptosis, calcium homeostasis, calcification and fibrosis and in different
      signaling pathways linked or not to mitochondrial function. The most significant
      changes were observed in ketone body and acetate metabolism, NADH shuttle
      proteins, amino-acid metabolism proteins and respiratory enzymes. Several of
      these changes are consistent with the known phenotype of desmin deficiency.

PMID- 15733907
TI  - Increased late sodium current in myocytes from a canine heart failure model and
      from failing human heart.
AB  - Electrophysiological remodeling of ion channels in heart failure causes action
      potential prolongation and plays a role in arrhythmia mechanism. The importance
      of down-regulation of potassium currents is well-known, but a role for Na current
      (I(Na)) in heart failure is less well established. We studied I(Na) in heart
      failure ventricular cells from a canine pacing model of heart failure and also
      from explanted failing human hearts. Peak I(Na) density was significantly
      decreased by 39% and 57% in the dog model and in human heart failure,
      respectively. The kinetics of peak I(Na) were not different in heart failure.
      Late I(Na) was measured 750 ms after the initial depolarization as the saxitoxin
      (STX)-sensitive current and also as the current remaining after contaminating
      currents were blocked. Late I(Na) as a percentage of the peak I(Na) was
      significantly increased in both conditions. In dogs, STX sensitive late I(Na) was
      0.5 +/- 0.1% n = 16 cells from eight normal hearts and 3.4 +/- 1.4% n = 12 cells
      from seven failing hearts; in humans, it was 0.2 +/- 0.1% n = 4 cells from two
      normal hearts and 2.4 +/- 0.5% n = 10 cells from three human failing hearts (-40
      mV). Quantitative measures of mRNA including RNase protection assays and real
      time quantitative PCR in the dog model showed no differences for different alpha
      subunit isoforms (NaV1.1, 1.3, 1.5) and for the beta1 and beta2 subunits. This
      suggests neither alpha subunit isoform switching nor altered beta subunit
      expression is a mechanism for increased late I(Na). We conclude that a peak I(Na)
      is decreased, and non-inactivating late I(Na) is increased in heart failure and
      this may contribute to action potential prolongation and the generation of
      arrhythmia.

PMID- 15733908
TI  - Apoptosis-modulating interaction of the neuregulin/erbB pathway with
      anthracyclines in regulating Bcl-xS and Bcl-xL in cardiomyocytes.
AB  - During chemotherapy with anthracyclines, attenuated neuregulin signaling by the
      erbB2 receptor inactivating antibody Trastuzumab enhances the heart failure risk.
      We compared the effects of attenuated neuregulin/erbB signaling and of
      daunorubicin on splicing of the Bcl-x gene and on mitochondrial activation of
      apoptosis in cardiomyocytes. Attenuating erbB signals in cultured neonatal rat
      cardiomyocytes by the erbB2 antagonist tyrphostin AG825, by the erbB1/4
      antagonist AG1478 or by antisense-induced lowering of erbB2 receptors resulted in
      an augmented Bcl-xS/Bcl-xL ratio, mitochondrial release of cytochrome c,
      activation of caspase 9 and caspase 3, and nucleosome-sized DNA fragmentation. A
      similar DNA fragmentation and caspase 3 activation was induced by TNF-alpha, but
      without Bcl-xS/Bcl-xL increase, cytochrome c release or caspase 9 activation. A
      BH4-domain containing HIV TAT fusion protein added to cardiomyocytes under
      attenuated erbB signaling lowered the enhanced Bcl-xS/Bcl-xL ratio, the
      cytochrome c release, the caspase 3 activation and the DNA fragmentation, while
      apoptosis was not modified by the fusion protein in TNF-alpha treated
      cardiomyocytes. Enhancement of Bcl-xS/Bcl-xL by reducing Bcl-xL via siRNA
      transfection mimicked the mitochondrial apoptotic activation due to erbB signal
      attenuation. Daunorubicin also caused Bcl-xS/Bcl-xL enhancement and mitochondrial
      apoptotic activation in cultured cardiomyocytes; this was attenuated by BH4
      fusion protein or by neuregulin-1 and augmented by siRNA-mediated Bcl-xL
      lowering. We conclude that activation of mitochondrial apoptosis due to altered
      Bcl-x splicing contributes as a common mechanism of anthracyclines and erbB
      signal attenuation to the enhanced heart failure risk under this combination.

PMID- 15733909
TI  - The effect of extracellular matrix on embryonic stem cell-derived cardiomyocytes.
AB  - Extracellular matrix (ECM) components significantly influence the growth
      characteristics of cardiomyocytes, development of spontaneous contractile
      activity and morphologic differentiation. The present study involves
      characterization of ES cell-derived cardiomyocytes cultured on different ECMs. We
      hypothesized that cardiogel, which is a naturally occurring ECM containing a
      complex mixture of laminin, fibronectin may better support ES cell-derived
      cardiomyocytes maturation in terms of chronotropic characteristics and
      subcellular structure development. Spontaneously differentiated cardiomyocytes
      from 7-day embryoid bodies (EBs) derived from mouse ES cells line Royan B1
      (C57BL/6) were cultured on commercial ECM (matrigel), a fibroblast-derived ECM
      (cardiogel), and control (without ECM) for 7 + 21 days. The growth
      characteristics of cardiomyocytes were assessed by immunocytochemistry, reverse
      transcription polymerase chain reaction (RT-PCR), positive and negative
      chronotropic drugs and transmission electron microscopy (TEM). The spontaneously
      beating cells expressed markers characteristic of cardiomyocytes including alpha
      actinin, desmin, troponin-I, sarcomeric myosin heavy chain (MHC), pan-cadherin,
      connexin-43, cardiac alpha-MHC, cardiac beta-MHC, atrial natriuretic factor (ANF)
      and myosin light chain isoform-2V (MLC-2V). In addition, spontaneous beating of
      cardiomyocytes on both ECMs was enhanced by treatment of cells with isopernaline,
      while reduced more on matrigel, by carbacol when compared with control and
      cardiogel. However, the change in beating was similar in all groups upon
      treatment with phenylephrine and/or Bay-K. Ultrastructure analysis showed
      myofibrillar bundle organization and exhibited intercalated discs, T-tubules, Z-,
      A-, I-, H- and M-bands and the showed earlier maturation of the cardiomyocytes on
      cardiogel. We conclude that substructurally matured cardiomyocytes can be
      produced from ES cells and the cardiac fibroblast-derived ECM (cardiogel)
      supported earlier maturation of ES-derived cardiomyocytes, in terms of
      chronotropic characteristics and subcellular structure development.

PMID- 15733910
TI  - IL-1beta and TNF-alpha upregulate angiotensin II type 1 (AT1) receptors on
      cardiac fibroblasts and are associated with increased AT1 density in the post-MI
      heart.
AB  - Angiotensin (Ang) II plays an important role in post-myocardial infarction (MI)
      cardiac remodeling. The Ang II type 1 (AT(1)) receptor which mediates most Ang II
      effects is upregulated on non-myocytes in the post-MI heart. We have shown that
      pro-inflammatory cytokines increase AT(1) receptor density on cardiac fibroblasts
      through a mechanism involving NF-kappaB activation. This study examines the in
      vitro kinetics of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta
      (IL-1beta) induced AT(1) receptor upregulation in neonatal rat cardiac
      fibroblasts and assesses temporal and spatial associations between the appearance
      of these agents and increased AT(1) receptor density post-MI. The results show
      that IL-1beta more rapidly induces AT(1) receptor upregulation than does TNF
      alpha, an effect that can be mimicked by a NF-kappaB-dependent luciferase
      reporter gene. Moreover, the effects of these pro-inflammatory cytokines are
      additive. Using immunohistochemistry in the post-MI rat heart we found strong
      temporal and spatial correlations between TNF-alpha, IL-1beta and AT(1) receptor
      proteins in the peri-infarction (PI) zone in fibroblasts and macrophages.
      Labeling intensity for the cytokines and the AT(1) receptor increased from 1 to 7
      days post-MI in the PI zone in conjunction with replacement scar formation. This
      labeling persisted in non-myocytes bordering the scar for up to 83 days post-MI.
      These findings suggest that IL-1beta and TNF-alpha act coordinately to increase
      AT(1) receptor density on non-myocytes in the post-MI heart and that this effect
      may contribute to extracellular matrix remodeling and fibrosis.

PMID- 15733911
TI  - 150-kDa oxygen-regulated protein attenuates myocardial ischemia-reperfusion
      injury in rat heart.
AB  - Early contractile dysfunction and the later death of cardiomyocytes are two major
      problems that can follow myocardial infarction or major cardiovascular surgery
      that demands ischemic arrest of the heart. Here, we found that 24 h of hypoxia
      and 1 h of reoxygenation induced the expression of the chaperone ORP150 in
      cultured rat cardiomyocytes. Inhibition of its induction using an adenovirus to
      express anti-sense ORP150 significantly enhanced the hypoxia-reoxygenation
      induced cardiomyocyte death; cell death was reduced by overexpressing ORP150.
      Decreased levels of ORP150 expression also enhanced caspase-3 and -8 activation,
      cytochrome-c release, and DNA fragmentation, suggesting that this chaperone
      regulates apoptotic cell death. In contrast, increasing the expression of ORP150
      in the cardiomyocytes had the opposite effect on the expression of these
      molecules. Moreover, apoptotic cell death initiated by myocardial ischemia
      reperfusion (I/R) was significantly inhibited in vivo by transfecting an ORP150
      expression plasmid into whole rat heart using the hemagglutinating virus of Japan
      (HVJ)-liposome method. Interestingly, ORP150 seemed to preserve calcium
      homeostasis in cardiomyocytes that underwent ischemia-reoxygenation in vitro.
      Calpain activity in the cardiomyocytes was enhanced by anti-sense ORP150 and
      suppressed by sense ORP150. Finally, we examined the functional recovery of rat
      hearts that overexpressed ORP150 or GFP protein and were subjected to I/R; we
      found that ORP150 preserved early contractile function after transient ischemia.
      Our results indicated cytoprotective roles for ORP150 in rat heart and suggested
      a therapeutic role for the protein both in preventing cardiomyocyte death and in
      preserving contractile function after ischemic damage.

PMID- 15733912
TI  - Endothelin-converting enzyme-1-mediated signaling in adult rat ventricular
      myocyte contractility and apoptosis during sepsis.
AB  - We hypothesized that modulation of endothelin-converting enzyme-1 (ECE-1)
      activity would affect phosphorylation of p38-mitogen activated protein kinase
      (p38-MAPK) and potentiate apoptosis in adult rat ventricular myocytes (ARVMs)
      during sepsis. The activity of ECE-1 in ARVMs was altered by increasing the
      substrate availability for ECE-1 by exogenous administration of bigendothelin-1
      (bigET-1, 100 nM) and by inhibiting ECE-1 using FR901533 (10 microM) for 24-h.
      FR901533 significantly decreased the concentration of ET-1 in both sham and
      sepsis groups. FR901533 decreased p38-MAPK phosphorylation in sepsis but not in
      sham group. BigET-1 upregulated p38-MAPK phosphorylation, produced hypertrophy,
      decreased cell viability and reversed FR901533-induced down-regulation of p38
      MAPK phosphorylation in both groups. Although, FR901533 did not affect cell cross
      sectional area, it significantly reduced the viability of ARVM in both groups.
      The peak shortening of sham ARVMs was elevated by bigET-1, FR901533 and
      pretreatment with FR901533 followed by bigET-1. However, the contractility of
      septic ARVMs was not altered by either bigET-1 or FR901533 treatments per se.
      Septic ARVM exhibited significantly increased caspase-3 activity at 12 and 24-h.
      Pretreatment with FR901533 significantly elevated caspase-3 activity in both sham
      and sepsis group. The data demonstrated that bigET-1-induced hypertrophy in
      septic ARVM correlates with an ECE-1 dependent-activation of p38-MAPK. The
      results suggest that non-responsiveness of ARVM to bigET-1 is due to ECE-1
      dependent apoptosis. We concluded that ECE-1 may play a crucial role in ARVM
      dysfunction via increased caspase-3 activity and p38-MAPK phosphorylation during
      sepsis.

PMID- 15733913
TI  - Two domains of MalT, the activator of the Escherichia coli maltose regulon, bear
      determinants essential for anti-activation by MalK.
AB  - MalT, the dedicated transcriptional activator of the maltose regulon in
      Escherichia coli, is subject to multiple controls. Maltotriose, the inducer,
      promotes MalT self-association, a critical step in promoter binding, whereas
      three proteins acting as negative allosteric effectors (MalK, the ABC-component
      of the maltodextrin transporter, MalY, and Aes) antagonize maltotriose binding.
      All of these regulatory signals are integrated by a novel signal transduction
      module that comprises three out of the four MalT structural domains: DT1, the ATP
      binding domain that contains determinants recognized by the negative effectors,
      DT2, and DT3, the maltotriose-binding domain. For a better insight into the role
      of DT3 in signal integration, we PCR mutagenized the DT3-encoding region and
      screened for gain of function mutations in a malK+ strain in the absence of
      repression by MalY or Aes. Most of the mutations isolated alter one of seven
      residues that are located in DT3 helices 10 and 11, or in the turn between them
      and delineate a surface-exposed motif. In vivo and in vitro analyses revealed
      that the substitutions altering the so-called H10/H11 motif do not affect the
      ability of MalT to activate transcription or its sensitivity to MalY and Aes, but
      dramatically decrease its sensitivity to MalK. We propose that MalT/MalK
      interaction might involve two distinct contact sites on each partner. These sites
      would be located in DT1 and DT3 of MalT, and in the nucleotide-binding domain and
      the regulatory domain of MalK. Such a two-point interaction model would explain
      how the regulatory activity of MalK might be coupled to transport.

PMID- 15733914
TI  - The structure of the excisionase (Xis) protein from conjugative transposon Tn916
      provides insights into the regulation of heterobivalent tyrosine recombinases.
AB  - Heterobivalent tyrosine recombinases play a prominent role in numerous
      bacteriophage and transposon recombination systems. Their enzymatic activities
      are frequently regulated at a structural level by excisionase factors, which
      alter the ability of the recombinase to assemble into higher-order recombinogenic
      nucleoprotein structures. The Tn916 conjugative transposon spreads antibiotic
      resistance in pathogenic bacteria and is mobilized by a heterobivalent
      recombinase (Tn916Int), whose activity is regulated by an excisionase factor
      (Tn916Xis). Unlike the well-characterized (lambda)Xis excisionase from
      bacteriophage lambda, Tn916Xis stimulates excision in vitro and in Escherichia
      coli only modestly. To gain insights into this functional difference, we have
      performed in vitro DNA-binding studies of Tn916Xis and Tn916Int, and we have
      solved the solution structure of Tn916Xis. We show that the heterobivalent
      Tn916Int protein is capable of bridging the DR2-type and core-type sites on the
      left arm of the tranpsoson. Consistent with the notion that Tn916Int is regulated
      only loosely, we find that Tn916Xis binding does not alter the stability of DR2
      Tn916Int-core bridges or the ability of Tn916Int to recognize the arms of the
      transposon in vitro. Despite a high degree of divergence at the primary sequence
      level, we show that Tn916Xis and (lambda)Xis adopt related prokaryotic winged
      helix structures. However, they differ at their C termini, with Tn916Xis
      replacing the flexible integrase contacting tail found in (lambda)Xis with a
      positively charged alpha-helix. This difference provides a structural explanation
      for why Tn916Xis does not interact cooperatively with its cognate integrase in
      vitro, and reveals how subtle changes in the winged-helix fold can modulate the
      functional properties of excisionase factors.

PMID- 15733916
TI  - Atomic force microscopy analysis of icosahedral virus RNA.
AB  - Single-stranded genomic RNAs from four icosahedral viruses (poliovirus, turnip
      yellow mosaic virus (TYMV), brome mosaic virus (BMV), and satellite tobacco
      mosaic virus (STMV)) along with the RNA from the helical tobacco mosaic virus
      (TMV) were extracted using phenol/chloroform. The RNAs were imaged using atomic
      force microscopy (AFM) under dynamic conditions in which the RNA was observed to
      unfold. RNAs from the four icosahedral viruses initially exhibited highly
      condensed, uniform spherical shapes with diameters consistent with those expected
      from the interiors of their respective capsids. Upon incubation at 26 degrees C,
      poliovirus RNA gradually transformed into chains of globular domains having the
      appearance of thick, irregularly segmented fibers. These ultimately unwound
      further to reveal segmented portions of the fibers connected by single strands of
      RNA of 0.5-1 nm thickness. Virtually the same transformations were shown by TYMV
      and BMV RNA, and with heating, the RNA from STMV. Upon cooling, the chains of
      domains of poliovirus RNA and STMV RNA condensed and re-formed their original
      spherical shapes. TMV RNAs initially appeared as single-stranded threads of 0.5
      1.0 nm diameter but took on the structure of the multidomain chains upon further
      incubation at room temperature. These ultimately condensed into short, thick
      chains of larger domains. Our observations suggest that classical extraction of
      RNA from icosahedral virions produces little effect on overall conformation. As
      tertiary structure is lost however, it is evident that secondary structural
      elements are arranged in a sequential, linear fashion along the polynucleotide
      chain. At least in the case of poliovirus and STMV, the process of tertiary
      structure re-formation from the linear chain of secondary structural domains
      proceeds in the absence of protein. RNA base sequence, therefore, may be
      sufficient to encode the conformation of the encapsidated RNA even in the absence
      of coat proteins.

PMID- 15733915
TI  - Interaction of the eukaryotic pore-forming cytolysin equinatoxin II with model
      membranes: 19F NMR studies.
AB  - Sea anemones produce a family of 18-20 kDa proteins, the actinoporins, which lyse
      cells by forming pores in cell membranes. Sphingomyelin plays an important role
      in their lytic activity, with membranes lacking this lipid being largely
      refractory to these toxins. As a means of characterising membrane binding by the
      actinoporin equinatoxin II (EqTII), we have used 19F NMR to probe the environment
      of Trp residues in the presence of micelles and bicelles. Trp was chosen as
      previous data from mutational studies and truncated analogues had identified the
      N-terminal helix of EqTII and the surface aromatic cluster including tryptophan
      residues 112 and 116 as being important for membrane interactions. The five
      tryptophan residues were replaced with 5-fluorotryptophan and assigned by site
      directed mutagenesis. The 19F resonance of W112 was most affected in the presence
      of phospholipid micelles or bicelles, followed by W116, with further change
      induced by the addition of sphingomyelin. Although binding to phosphatidylcholine
      is not sufficient to enable pore formation in bilayer membranes, this interaction
      had a greater effect on the tryptophan residues in our studies than the
      subsequent interaction with sphingomyelin. Furthermore, sphingomyelin had a
      direct effect on EqTII in both model membranes, so its role in EqTII pore
      formation involves more than simply an indirect effect mediated via bulk lipid
      properties. The lack of change in chemical shift for W149 even in the presence of
      sphingomyelin indicates that, at least in the model membranes studied here,
      interaction with sphingomyelin was not sufficient to trigger dissociation of the
      N-terminal helix from the beta-sandwich, which forms the bulk of the protein.

PMID- 15733917
TI  - Extracting stacking interaction parameters for RNA from the data set of native
      structures.
AB  - A crucial step in the determination of the three-dimensional native structures of
      RNA is the prediction of their secondary structures, which are stable independent
      of the tertiary fold. Accurate prediction of the secondary structure requires
      context-dependent estimates of the interaction parameters. We have exploited the
      growing database of natively folded RNA structures in the Protein Data Bank (PDB)
      to obtain stacking interaction parameters using a knowledge-based approach.
      Remarkably, the calculated values of the resulting statistical potentials (SPs)
      are in excellent agreement with the parameters determined using measurements in
      small oligonucleotides. We validate the SPs by predicting 74% of the base-pairs
      in a dataset of structures using the ViennaRNA package. Interestingly, this
      number is similar to that obtained using the measured thermodynamic parameters.
      We also tested the efficacy of the SP in predicting secondary structure by using
      gapless threading, which we advocate as an alternative method for rapidly
      predicting RNA structures. For RNA molecules with less than 700 nucleotides,
      about 70% of the native base-pairs are correctly predicted. As a further
      validation of the SPs we calculated Z-scores, which measure the relative
      stability of the native state with respect to a manifold of higher free energy
      states. The computed Z-scores agree with estimates made using calorimetric
      measurements for a few RNA molecules. Structural analysis was used to rationalize
      the success and failures of SP and experimentally determined parameters. First,
      from the near perfect linear relationship between the number of native base-pairs
      and sequence length, we show that nearly 46% of nucleotides are not in stacks.
      Second, by analyzing the suboptimal structures that are generated in gapless
      threading we show that the SPs and experimentally determined parameters are most
      successful in predicting stacks that end in hairpins. These results show that
      further improvement in secondary structure prediction requires reliable estimates
      of interaction parameters for loops, bulges, and stacks that do not end in
      hairpins.

PMID- 15733918
TI  - Bacteriophage lambda terminase: alterations of the high-affinity ATPase affect
      viral DNA packaging.
AB  - DNA packaging by large DNA viruses such as the tailed bacteriophages and the
      herpesviruses involves DNA translocation into a preformed protein shell, called
      the prohead. Translocation is driven by an ATP hydrolysis-powered DNA packaging
      motor. The bacteriophages encode a heterodimeric viral DNA packaging protein,
      called terminase. The terminases have an ATPase center located in the N terminus
      of the large subunit implicated in DNA translocation. In previous work with phage
      lambda, lethal mutations that changed ATP-reactive residues 46 and 84 of gpA, the
      large terminase subunit, were studied. These mutant enzymes retained the
      terminase endonuclease and helicase activities, but had severe defects in virion
      assembly, and lacked the terminase high-affinity ATPase activity. Surprisingly,
      in the work described here, we found that enzymes with the conservative gpA
      changes Y46F and Y46A had only mild packaging defects. These mild defects
      contrast with their profound virion assembly defects. Thus, these mutant enzymes
      have, in addition to the mild DNA packaging defects, a severe post-DNA packaging
      defect. In contrast, the gpA K84A enzyme had similar virion assembly and DNA
      packaging defects. The DNA packaging energy budget, i.e. DNA packaged/ATP
      hydrolyzed, was unchanged for the mutant enzymes, indicating that DNA
      translocation is tightly coupled to ATP hydrolysis. A model is proposed in which
      gpA residues 46 and 84 are important for terminase's high-affinity ATPase
      activity. Assembly of the translocation complex remodels this ATPase so that
      residues 46 and 84 are not crucial for the activated translocation ATPase.
      Changing gpA residues 46 and 84 primarily affects assembly, rather than the
      activity, of the translocation complex.

PMID- 15733919
TI  - Patterns that define the four domains conserved in known and novel isoforms of
      the protein import receptor Tom20.
AB  - Tom20 is the master receptor for protein import into mitochondria. Analysis of
      motifs present in Tom20 sequences from fungi and animals found several highly
      conserved regions, including features of the transmembrane segment, the ligand
      binding domain and functionally important flexible segments at the N terminus and
      the C terminus of the protein. Hidden Markov model searches of genome sequence
      data revealed novel isoforms of Tom20 in vertebrate and invertebrate animals. A
      three-dimensional comparative model of the novel type I Tom20, based on the
      structurally characterized type II isoform, shows important differences in the
      amino acid residues lining the ligand-binding groove, where the type I protein
      from animals is more similar to the fungal form of Tom20. Given that the two
      receptor types from mouse interact with the same set of precursor protein
      substrates, comparative analysis of the substrate-binding site provides unique
      insight into the mechanism of substrate recognition. No Tom20-related protein was
      found in genome sequence data from plants or protozoans, suggesting the receptor
      Tom20 evolved after the split of animals and fungi from the main lineage of
      eukaryotes.

PMID- 15733920
TI  - Molecular structure of D-hydantoinase from Bacillus sp. AR9: evidence for mercury
      inhibition.
AB  - Stereospecific conversion of hydantoins into their carbamoyl acid derivatives
      could be achieved by using the enzyme hydantoinase. Specific hydantoinases
      convert either the D-form or the L-form of the hydantoin and the amino acids
      responsible for stereospecificity have not been identified. Structural studies on
      hydantoinases from a few bacterial species were published recently. The structure
      of a thermostable D-hydantoinase from Bacillus sp. AR9 (bar9HYD) was solved to
      2.3 angstroms resolution. The usual modification of carboxylation of the active
      site residue Lys150 did not happen in bar9HYD. Two manganese ions were modelled
      in the active site. Through biochemical studies, it was shown that mercury
      inhibits the activity of the enzyme. The mercury derivative provided some
      information about the binding site of the mercuric inhibitors and a possible
      reason for inhibition is presented.

PMID- 15733921
TI  - Engineering high affinity superantigens by phage display.
AB  - Protein L (PpL) is a B-cell superantigen from Peptostreptococcus magnus known to
      bind to mammalian Vkappa light chains. PpL from P.magnus strain 312 comprises
      five homologous immunoglobulin (Ig) binding domains. We first analysed the
      binding of the individual domains (B1-B5) of PpL(312) to human Vkappa light
      chains (huVkappa) subtypes 1 (huVkappaI) and 3 (huVkappaIII). Using a combination
      of rational design and phage selection we isolated mutants of the N-terminal B1
      domain with a 14-fold increased affinity for huVkappa1 (B1kappa1) and >tenfold
      increased affinity for huVkappaIII (B1kappa3). We investigated the potential of
      the selected domains, in particular the B1kappa1 domain, as reagents in
      immunochemistry and immunotherapy. B1kappa1 proved a superior reagent than the
      wild-type domain, allowing up to tenfold more sensitive detection of human Vkappa
      antibody fragments in ELISA. A fusion protein of B1kappa1 with a human Vlambda
      antibody scFv fragment promoted the efficient recruitment of antibody encoded
      effector functions including complement, mononuclear phagocyte respiratory burst
      and phagocytosis through retargeting of IgGkappa and IgMkappa. Our results
      suggest that superantigens with improved affinity and/or specificity are easily
      accessible through protein engineering. Such engineered superantigens should
      prove useful as reagents in immunochemistry and may have potential as agents in
      immunotherapy.

PMID- 15733922
TI  - The crystal structure of the pyoverdine outer membrane receptor FpvA from
      Pseudomonas aeruginosa at 3.6 angstroms resolution.
AB  - The pyoverdine outer membrane receptor FpvA from Pseudomonas aeruginosa
      translocates ferric-pyoverdine across the outer membrane via an energy consuming
      mechanism that involves the inner membrane energy transducing complex of TonB
      ExbB-ExbD and the proton motive force. We solved the crystal structure of FpvA
      loaded with iron-free pyoverdine at 3.6 angstroms resolution. The pyoverdine
      receptor is folded in two domains: a transmembrane 22-stranded beta-barrel domain
      occluded by an N-terminal domain containing a mixed four-stranded beta-sheet (the
      plug). The beta-strands of the barrel are connected by long extracellular loops
      and short periplasmic turns. The iron-free pyoverdine is bound at the surface of
      the receptor in a pocket lined with aromatic residues while the extracellular
      loops do not completely cover the pyoverdine binding site. The TonB box, which is
      involved in intermolecular contacts with the TonB protein of the inner membrane,
      is observed in an extended conformation. Comparison of this first reported
      structure of an iron-siderophore transporter from a bacterium other than
      Escherichia coli with the known structures of the E.coli TonB-dependent
      transporters reveals a high structural homology and suggests that a common
      sensing mechanism exists for the iron-loading status in all bacterial iron
      siderophore transporters.

PMID- 15733923
TI  - Structure of the thermolabile mutant aldolase B, A149P: molecular basis of
      hereditary fructose intolerance.
AB  - Hereditary fructose intolerance (HFI) is a potentially lethal inborn error in
      metabolism caused by mutations in the aldolase B gene, which is critical for
      gluconeogenesis and fructose metabolism. The most common mutation, which accounts
      for 53% of HFI alleles identified worldwide, results in substitution of Pro for
      Ala at position 149. Structural and functional investigations of human aldolase B
      with the A149P substitution (AP-aldolase) have shown that the mutation leads to
      losses in thermal stability, quaternary structure, and activity. X-ray
      crystallography is used to reveal the structural basis of these perturbations.
      Crystals of AP-aldolase are grown at two temperatures (4 degrees C and 18 degrees
      C), and the structure solved to 3.0 angstroms resolution, using the wild-type
      structure as the phasing model. The structures reveal that the single residue
      substitution, A149P, causes molecular disorder around the site of mutation
      (residues 148-159), which is propagated to three adjacent beta-strand and loop
      regions (residues 110-129, 189-199, 235-242). Disorder in the 110-129-loop
      region, which comprises one subunit-subunit interface, provides an explanation
      for the disrupted quaternary structure and thermal instability. Greater
      structural perturbation, particularly at a Glu189-Arg148 salt bridge in the
      active-site architecture, is observed in the structure determined at 18 degrees
      C, which could explain the temperature-dependent loss in activity. The disorder
      revealed in these structures is far greater than that predicted by homology
      modeling and underscores the difficulties in predicting perturbations of protein
      structure and function by homology modeling alone. The AP-aldolase structure
      reveals the molecular basis of a hereditary disease and represents one of only a
      few structures known for mutant proteins at the root of the thousands of other
      inherited disorders.

PMID- 15733925
TI  - Effect of the structure of the denatured state of lysozyme on the aggregation
      reaction at the early stages of folding from the reduced form.
AB  - We previously demonstrated that the hydrophobic clusters present in hen lysozyme
      under denaturing conditions were disrupted by the mutation of Trp62 to Gly
      (W62G). In order to examine the effects of the structure of the denatured state
      of W62G lysozyme on folding, we analyzed the early events in the folding of
      reduced W62G lysozyme in detail. From the exchange measurements of disulfide
      bonds using the variants containing a pair of cysteine residues (1SS), it was
      found that the formation of disulfide bond in the W62G1SS lysozyme was not
      accompanied by a prominent interaction between amino acid residues, indicating
      that the disruption of the hydrophobic core led to the random folding at the
      early stages in the process of folding of the reduced lysozyme. On the other
      hand, analyses of the oxidative-renaturation of reduced W62G lysozymes, as well
      as measurements of the extent of aggregation of the reduced and carboxy amido
      methylated W62G lysozyme, indicated that the formation of an aggregate is more
      prominent in the reduced W62G lysozyme than in the reduced wild-type lysozyme.
      Moreover, a lag phase was detected in the oxidative-renaturation of reduced W62G
      lysozyme, as based on observations of the recovery of activity. The simulation of
      the folding process indicated that intermediates were present at the early stages
      in the folding of the reduced W62G lysozyme. These results suggest that the
      presence of the intermediates was derived from the random folding at the early
      stages in the folding process of reduced W62G lysozyme due to the disruption of
      the structure of the denatured state. Folding thus appears to have been
      kinetically delayed by these processes, which then led to the significant
      aggregation of reduced lysozyme. Moreover, from the analysis of amyloid
      aggregation of the reduced lysozymes, it was suggested that the disruption of the
      residual structure in denatured state by W62G mutation deterred the formation of
      the amyloid fibrils of lysozyme.

PMID- 15733924
TI  - Are neuronal SNARE proteins Ca2+ sensors?
AB  - The neuronal SNARE complex formed by synaptobrevin, syntaxin and SNAP-25 plays a
      central role in Ca2+-triggered neurotransmitter release. The SNARE complex
      contains several potential Ca2+-binding sites on the surface, suggesting that the
      SNAREs may be involved directly in Ca2+-binding during release. Indeed,
      overexpression of SNAP-25 bearing mutations in two putative Ca2+ ligands
      (E170A/Q177A) causes a decrease in the Ca2+-cooperativity of exocytosis in
      chromaffin cells. To test whether the SNARE complex might function in Ca2+
      sensing, we analyzed its Ca2+-binding properties using transverse relaxation
      optimized spectroscopy (TROSY)-based NMR methods. Several Ca2+-binding sites are
      found on the surface of the SNARE complex, but most of them are not specific for
      Ca2+ and all have very low affinity. Moreover, we find that the E170A/Q177A SNAP
      25 mutation does not alter interactions between the SNAREs and the Ca2+ sensor
      synaptotagmin 1, but severely impairs SNARE complex assembly. These results
      suggest that the SNAREs do not act directly as Ca2+ receptors but SNARE complex
      assembly is coupled tightly to Ca2+-sensing during neurotransmitter release.

PMID- 15733926
TI  - Sequence determinants of a transmembrane proton channel: an inverse relationship
      between stability and function.
AB  - The driving forces behind the folding processes of integral membrane proteins
      after insertion into the bilayer, is currently under debate. The M2 protein from
      the influenza A virus is an ideal system to study lateral association of
      transmembrane helices. Its proton selective channel is essential for virus
      functioning and a target of the drug amantadine. A 25 residue transmembrane
      fragment of M2, M2TM, forms a four-helix bundle in vivo and in various detergents
      and phospholipid bilayers. Presented here are the energetic consequences for
      mutations made to the helix/helix interfaces of the M2TM tetramer. Analytical
      ultracentrifugation has been used to determine the effect of ten single-site
      mutations, to either alanine or phenylalanine, on the oligomeric state and the
      free energy of M2TM in the absence and the presence of amantadine. It was
      expected that many of these mutations would perturb the M2TM stability and
      tetrameric integrity. Interestingly, none of the mutations destabilize
      tetramerization. This finding suggests that M2 sacrifices stability to preserve
      its functions, which require rapid and specific interchange between distinct
      conformations involved in gating and proton conduction. Mutations might therefore
      restrict the full range of conformations by stabilizing a given native or non
      native conformational state. In order to assess one specific conformation of the
      tetramer, we measured the binding of amantadine to the resting state of the
      channel, and examined the overall free energy of assembly of the amantadine bound
      tetramer. All of the mutations destabilized amantadine binding or were
      isoenergetic. We also find that large to small residue changes destabilize the
      amantadine bound tetramer whereas mutations to side-chains of similar volume
      stabilize this conformation. A structural model of the amantadine bound state of
      M2TM was generated using a novel protocol that optimizes a structure for an
      ensemble of neutral and disruptive mutations. The model structure is consistent
      with the mutational data.

PMID- 15733927
TI  - Structural basis for the energetics of jacalin-sugar interactions: promiscuity
      versus specificity.
AB  - Jacalin, a tetrameric lectin, is one of the two lectins present in jackfruit
      (Artocarpus integrifolia) seeds. Its crystal structure revealed, for the first
      time, the occurrence of the beta-prism I fold in lectins. The structure led to
      the elucidation of the crucial role of a new N terminus generated by post
      translational proteolysis for the lectin's specificity for galactose. Subsequent
      X-ray studies on other carbohydrate complexes showed that the extended binding
      site of jacalin consisted of, in addition to the primary binding site, a
      hydrophobic secondary site A composed of aromatic residues and a secondary site B
      involved mainly in water-bridges. A recent investigation involving surface
      plasmon resonance and the X-ray analysis of a methyl-alpha-mannose complex, had
      led to a suggestion of promiscuity in the lectin's sugar specificity. To explore
      this suggestion further, detailed isothermal titration calorimetric studies on
      the interaction of galactose (Gal), mannose (Man), glucose (Glc), Me-alpha-Gal,
      Me-alpha-Man, Me-alpha-Glc and other mono- and oligosaccharides of biological
      relevance and crystallographic studies on the jacalin-Me-alpha-Glc complex and a
      new form of the jacalin-Me-alpha-Man complex, have been carried out. The binding
      affinity of Me-alpha-Man is 20 times weaker than that of Me-alpha-Gal. The
      corresponding number is 27, when the binding affinities of Gal and Me-alpha-Gal,
      and those of Man and Me-alpha-Man are compared. Glucose (Glc) shows no measurable
      binding, while the binding affinity of Me-alpha-Glc is slightly less than that of
      Me-alpha-Man. The available crystal structures of jacalin-sugar complexes provide
      a convincing explanation for the energetics of binding in terms of interactions
      at the primary binding site and secondary site A. The other sugars used in
      calorimetric studies show no detectable binding to jacalin. These results and
      other available evidence suggest that jacalin is specific to O-glycans and its
      affinity to N-glycans is extremely weak or non-existent and therefore of limited
      value in processes involving biological recognition.

PMID- 15733928
TI  - High resolution crystal structures of human cytosolic thiolase (CT): a comparison
      of the active sites of human CT, bacterial thiolase, and bacterial KAS I.
AB  - Thiolases belong to a superfamily of condensing enzymes that includes also beta
      ketoacyl acyl carrier protein synthases (KAS enzymes), involved in fatty acid
      synthesis. Here, we describe the high resolution structure of human cytosolic
      acetoacetyl-CoA thiolase (CT), both unliganded (at 2.3 angstroms resolution) and
      in complex with CoA (at 1.6 angstroms resolution). CT catalyses the condensation
      of two molecules of acetyl-CoA to acetoacetyl-CoA, which is the first reaction of
      the metabolic pathway leading to the synthesis of cholesterol. CT is a
      homotetramer of exact 222 symmetry. There is an excess of positively charged
      residues at the interdimer surface leading towards the CoA-binding pocket,
      possibly important for the efficient capture of substrates. The geometry of the
      catalytic site, including the three catalytic residues Cys92, His 353, Cys383,
      and the two oxyanion holes, is highly conserved between the human and bacterial
      Zoogloea ramigera thiolase. In human CT, the first oxyanion hole is formed by
      Wat38 (stabilised by Asn321) and NE2(His353), and the second by N(Cys92) and
      N(Gly385). The active site of this superfamily is constructed on top of four
      active site loops, near Cys92, Asn321, His353, and Cys383, respectively. These
      loops were used for the superpositioning of CT on the bacterial thiolase and on
      the Escherichia coli KAS I. This comparison indicates that the two thiolase
      oxyanion holes also exist in KAS I at topologically equivalent positions.
      Interestingly, the hydrogen bonding interactions at the first oxyanion hole are
      different in thiolase and KAS I. In KAS I, the hydrogen bonding partners are two
      histidine NE2 atoms, instead of a water and a NE2 side-chain atom in thiolase.
      The second oxyanion hole is in both structures shaped by corresponding main chain
      peptide NH-groups. The possible importance of bound water molecules at the
      catalytic site of thiolase for the reaction mechanism is discussed.

PMID- 15733929
TI  - Energy functions for protein design: adjustment with protein-protein complex
      affinities, models for the unfolded state, and negative design of solubility and
      specificity.
AB  - The development of the EGAD program and energy function for protein design is
      described. In contrast to most protein design methods, which require several
      empirical parameters or heuristics such as patterning of residues or rotamers,
      EGAD has a minimalist philosophy; it uses very few empirical factors to account
      for inaccuracies resulting from the use of fixed backbones and discrete rotamers
      in protein design calculations, and describes the unfolded state, aggregates, and
      alternative conformers explicitly with physical models instead of fitted
      parameters. This approach unveils important issues in protein design that are
      often camouflaged by heuristic-emphasizing methods. Inter-atom energies are
      modeled with the OPLS-AA all-atom forcefield, electrostatics with the generalized
      Born continuum model, and the hydrophobic effect with a solvent-accessible
      surface area-dependent term. Experimental characterization of proteins designed
      with an unmodified version of the energy function revealed problems with under
      packing, stability, aggregation, and structural specificity. Under-packing was
      addressed by modifying the van der Waals function. By optimizing only three
      parameters, the effects of >400 mutations on protein-protein complex formation
      were predicted to within 1.0 kcal mol(-1). As an independent test, this modified
      energy function was used to predict the stabilities of >1500 mutants to within
      1.0 kcal mol(-1); this required a physical model of the unfolded state that
      includes more interactions than traditional tripeptide-based models. Solubility
      and structural specificity were addressed with simple physical approximations of
      aggregation and conformational equilibria. The complete energy function can
      design protein sequences that have high levels of identity with their natural
      counterparts, and have predicted structural properties more consistent with
      soluble and uniquely folded proteins than the initial designs.

PMID- 15733930
TI  - Warm-up phenomenon and cardiac autonomic control in patients with coronary artery
      disease.
AB  - Decreased heart rate variability (HRV) and heart rate turbulence (HRT) are
      independent predictors of mortality after acute myocardial infarction (AMI).
      There are no previous studies on the relationship between warm-up phenomenon and
      cardiac autonomic control in stable coronary artery disease (CAD). We
      investigated the responses in HRV to repeated exercise induced ischemia and
      differences in global HRV and HRT in patients with and without adaptation to
      ischemia (warm-up phenomenon). Fifty male patients with CAD underwent two
      successive exercise tests with ambulatory electrocardiogram (ECG) recordings. HRV
      was evaluated using time and frequency domain measures and HRT was determined
      among patients with ventricular premature complexes (VPCs). The patients were
      divided in two groups on the basis of either positive (warm-up+) or negative
      (warm-up-) ischemia adaptation. Total power, ULF and VLF power and pNN50
      calculated from the entire ECG recording were higher in the group demonstrating
      warm-up phenomenon (P<0.05 for all). In the assessment of the four short-term
      stationary phases (pre-and post-test 1 and 2) total power, VLF power and pNN50
      were significantly higher in the warm-up positive group already at the baseline
      (P<0.05 for all). Furthermore, in the entire recordings total power, ULF and VLF
      power and SDNN correlated positively with the decrease in ischemic burden in the
      recovery phase (P<or=0.001 for all). No significant differences were found in HRT
      between the groups. Our results suggest that CAD patients demonstrating warm-up
      phenomenon have better cardiac autonomic control, and this correlates with the
      extent of ischemia adaptation. The true prognostic significance of this needs to
      be prospectively studied, however.

PMID- 15733931
TI  - Identical changes in Bax expression, but not Fas ligand expression, occur in
      structural luteolysis in gonadotropin releasing hormone agonist- and prolactin
      treated superovulated rats.
AB  - Structural luteolysis induced by gonadotropin releasing hormone agonist (GnRHa)
      or prolactin (PRL) is defined as histological involution of the corpus luteum. We
      reported that one of the mechanisms of structural luteolysis induced by PRL was
      tissue remodeling by matrix metalloproteinase (MMP) and also apoptosis in
      superovulated rats. We also reported that GnRHa induced structural luteolysis
      with elevation of MMP. In this study, we investigated whether GnRHa caused
      apoptosis in mature corpus luteum of superovulated rats and also examined the
      expression of apoptosis-related molecules (Fas, Fas ligand (FasL), Bcl-2, Bax).
      We gave 4-day GnRHa treatment 5 days after hCG injection to immature female rats
      treated with pregnant mare surum gonadotrophin (PMSG) and hCG to induce
      structural involution of mature corpus luteum. PMSG-hCG-treated rats without
      GnRHa treatment, rats treated with bromocryptine (Brom) to induce functional
      luteolysis and rats treated with Brom followed by PRL (Brom+PRL) to mimic the PRL
      surge to induce structural luteolysis as we previously reported were used for
      comparison. GnRHa treatment caused structural luteolysis characterized by
      structural involution, a decrease in the serum progestin level, and apoptotic
      bodies as well as structural luteolysis induced by Brom+PRL. FasL expression in
      corpora lutea was elevated after Brom treatment, but there was no elevation of
      FasL after GnRHa treatment started. FasL expression decreased and Bax expression
      increased in structural luteolysis induced by GnRHa as well as Brom+PRL
      treatment, although Fas and Bcl-2 expression did not change throughout the luteal
      phase. In summary, both GnRHa and Brom+PRL caused structural luteolysis, one of
      whose mechanisms was apoptosis with an increase in Bax expression, but not with
      an identical change in FasL expression. It is speculated that the significance in
      alteration of FasL may involve some mechanism other than apoptosis.

PMID- 15733932
TI  - Serotonergic disturbances in autistic disorder: L-5-hydroxytryptophan
      administration to autistic youngsters increases the blood concentrations of
      serotonin in patients but not in controls.
AB  - Some studies have suggested that disorders in the peripheral and central
      metabolism of serotonin (5-HT) may play a role in the pathophysiology of autistic
      disorder. This study examines the whole blood concentrations of 5-HT and 5
      hydroxy-indoleacetic acid (5-HIAA) in baseline conditions and during a challenge
      with L-5-OH-tryptophane (5-HTP; 4 mg/kg in non enteric-coated tablets), the
      precursor of 5-HT, in a study group of 18 male, post-pubertal, Caucasian autistic
      patients (age 13-19 y.; I.Q.>55) and 20 matched healthy volunteers. In baseline
      conditions, no significant differences in 5-HT or 5-HIAA levels could be found
      between autistic youngsters and normal controls. 5-HTP administration
      significantly increased the levels of 5-HT in autistic youngsters but not in
      normal controls. Following 5-HTP challenge the 5-HT levels were significantly
      higher in autistic patients than in healthy volunteers. After challenge with 5
      HTP, no significant differences were found in the concentrations of 5-HIAA or the
      test substance between autistic youngsters and normal controls. Differences in
      the peripheral metabolism of 5-HT which may not be observed in baseline
      conditions but which became clear after loading with 5-HTP, suggest that an
      increased synthesis of 5-HT from its precursor 5-HTP might be a one factor
      responsible for differences in the serotonergic system between autistic post
      pubertal youngsters and normal controls.

PMID- 15733933
TI  - Selenoureas and thioureas are effective superoxide radical scavengers in vitro.
AB  - Oxygen radicals, such as superoxide radicals, embellishing DNA, protein, lipids,
      etc., and carrying out the obstacle of the function of a cell is known. It
      depends for the oxidant level in the living body on the balance of a generation
      system and an elimination system of oxygen radicals, and research which controls
      an oxidant level in the living body is briskly done by taking in the substance
      which eliminates an oxygen radical. We investigated scavenging effects of
      superoxide radicals by selenoureas and thioureas using a highly sensitive and
      quantitative chemiluminescence method. At 330 nM, five selenoureas and five
      thioureas scavenged fractions of superoxide radicals (O2-) ranging from 8.4% to
      87.6%. Among five N,N-unsubstituted selenoureas and N,N-unsubstituted thioureas 1
      selenocarbamoylpiperidine and 1-thiocarbamoylpyrrolidine were the most effective
      scavengers. A possibility that selenoureas could use it as a new superoxide anion
      scavenging substance from the result of this research became clear.

PMID- 15733934
TI  - Protective effects of N-acetylserotonin against 6-hydroxydopamine-induced
      neurotoxicity.
AB  - The present work studied in vivo neuroprotective effects of n-acetylserotonin
      (NAS), the immediate precursor of melatonin, on the dopaminergic system, in rats
      lesioned with the unilateral intrastriatal injection of the neurotoxin 6
      hydroxydopamine (6-OHDA). Two weeks after the lesion, the dopamine receptor
      agonist, apomorphine, produced rotational asymmetry, and the NAS treatment
      significantly reduced the motor deficit following the apomorphine challenge. The
      apomorphine-induced rotational behavior was blocked by 84, 86 and 53% after NAS,
      at doses of 2, 5 and 10 mg/kg, i.p., respectively. The injection of 6-OHDA
      significantly decreased DA, DOPAC and HVA levels in the rat striatum. In
      contrast, the NAS (2, 5 and 10 mg/kg, i.p., daily for 7 days) treatment partially
      reversed the decreases caused by 6-OHDA, and the neurotransmitter levels were
      brought to approximately 50% of that observed in the contralateral sides. NAS was
      more efficient at the smaller doses. NAS (5 mg/kg) produced an up-regulation of
      D1 (37%) and D2 (37%) receptors associated with a decrease in Kd values.

PMID- 15733935
TI  - Fe(II)/Cu(I)-dependent P-type ATPase activity in the liver of Long-Evans cinnamon
      rats.
AB  - This study examined Fe(II)-dependent ATPase activity in OTG (octylthioglucoside) 
      treated microsomes isolated from Wistar and LEC rats. The ATPase activity of the
      liver OTG-microsomes from Wistar rats increased sharply in the 5-150 microM range
      of Fe(II) with a K0.5 value of 23.9+/-3.6 microM, while the activity of LEC rat
      liver microsomes increased with increasing Fe(II) up to 500 microM with a K0.5
      value of 64.4+/-8.1 microM. The K0.5 values for Fe(II)-dependent ATPase activity
      of spleen OTG-microsomes were nearly identical at 59.3 microM in the Wistar rat
      and 63.7 microM in the LEC rats with a similar level of activity at each Fe(II)
      concentration in both strains of animals. These results indicated that there are
      two types of Fe(II)-dependent ATPase with different Fe(II) sensitivity, a high
      sensitive (H) and a low sensitive (L) type, and that the H-type activity was
      specific to the liver. The H-type activity was, however, deficient in the liver
      of LEC rats that accumulate copper and iron in hepatocytes as a result of
      mutations in the Wilson's disease protein (WNDP). On the basis of these results,
      together with the similarity in optimal conditions required for full activity of
      the enzyme, we conclude that the Fe(II)-dependent ATPase (H-type) and WNDP may be
      identical.

PMID- 15733936
TI  - Cholinesterase activity in human pulmonary arteries and veins: correlation with
      mRNA levels.
AB  - Isolated intact human pulmonary arteries and veins were used to determine the
      acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) activities in the
      absence or presence of two selective cholinesterase (ChE) inhibitors, iso-OMPA or
      BW284c51, respectively. These results were compared with the mRNA levels for each
      enzyme in human pulmonary vessels. Total ChE activities measured in presence of
      acetylthiocholine (ACTI, 1 mM) in intact vascular preparations were 45+/-04 and
      114+/-07 mU/g tissue in human pulmonary arteries (n=14) and veins (n=14),
      respectively. These activities were completely abolished in presence of 10 microM
      neostigmine. In both types of vessels AChE and BChE activities were observed.
      These activities were at least 2-fold higher in human pulmonary veins when
      compared with arteries and were correlated with the accumulation of the
      corresponding transcripts (n=8). In each type of vessel, similar total ChE
      activities were detected in homogenized and intact preparations, while in human
      bronchial preparations this activity was 5-fold higher in homogenates than in
      intact preparations. Together these results provide evidence that the ChE
      activities in human pulmonary vessels may be extracellular and that the higher
      activity measured in veins as compared to arteries was associated with the
      differential accumulation of the corresponding transcripts.

PMID- 15733937
TI  - Antinociceptive properties of acetylenic thiophene and furan derivatives:
      evidence for the mechanism of action.
AB  - The aim of the present study was to evaluate the antinociceptive potential of the
      acetylenic thiophene and furan derivatives: 3-(furan-2-il) prop-2-yn-1-ol 1, 1
      (thiofen-2-il) pent-1yn-3-ol 2 and 4-(thiofen-2-il)-2-metilbut-3-yn-2-ol 3 on
      three different pain models in mice. The pain models evaluated were the acetic
      acid-induced writhing, capsaicin-induced pain and the tail immersion test. The
      possible mechanisms involved in the antinociceptive effect of these compounds
      were also investigated. Thus, the acetylenic thiophene and furan derivatives
      presented antinociceptive effect in the pain tests caused by chemical agents.
      Statistical analysis showed that compounds 1 and 3 increased the latency for tail
      withdrawal in the tail immersion test (phasic pain). Besides, the role of the
      opioidergic, muscarinic cholinergic and dopaminergic systems in the acetic acid
      induced writhing was examined. The antinociceptive effect of compounds 2 and 3
      was prevented by pretreatment with naloxone (1 mg/kg, s.c), but not by atropine
      (5 mg/kg, s.c) or metoclopramide (1 mg/kg, s.c). Neither naloxone nor
      metoclopramide prevented the antinociceptive effect caused by compound 1, while
      the pretreatment with atropine antagonized the antinociceptive action of this
      compound. The compounds 1-3 used in this study did not reveal any motor
      impairment to mice in the open field. The results suggest that compounds 2 and 3
      induced antinociception in the abdominal writhing test and that their effects are
      mediated by opiodergic receptors, while the antinociceptive effect of compound 1
      may involve muscarinic cholinergic receptors.

PMID- 15733938
TI  - Role of learning of open arm avoidance in the phenomenon of one-trial tolerance
      to the anxiolytic effect of chlordiazepoxide in mice.
AB  - A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or
      abolishes the anxiolytic efficacy of benzodiazepines on a second trial. Some
      possible explanations to the occurrence of this phenomenon (one-trial tolerance
      OTT) involve behavioral modifications thought to be consequence of some kind of
      learning in the first trial. In the present study, the influence of learning
      impairing situations on the effects of the benzodiazepine chlordiazepoxide on
      mice re-tested in the EPM is investigated. The results showed that: (1) as
      expected, the administration of chlordiazepoxide to mice re-tested in the EPM-
      under the same conditions of the first trial- failed to induce anxiolysis; (2) a
      decreased percent time in the open arms was observed on the second trial of mice
      exposed to both trials under the same experimental conditions; (3) neither the
      increase in open arm avoidance by mice re-exposed to the EPM nor the OTT to
      chlordiazepoxide effect were modified by administration of the amnestic agent
      scopolamine; (4) the decrement of the duration of the first trial to 1 min or the
      change in light and noise conditions in both trials counteracted the increase in
      open arm avoidance on trial 2; (5) none of the later procedures modified the
      phenomenon of OTT. Although not discarding the modulation exerted by other memory
      processes in the OTT phenomenon, the results indicate that situations that impair
      the learned avoidance response to the open arms in the EPM do not modify the
      phenomenon of OTT.

PMID- 15733939
TI  - Attenuation of N-methyl-N'-nitro-N-nitrosoguanidine induced genotoxicity and
      oxidative stress by tomato and garlic combination.
AB  - The protective effect of pretreatment with tomato and garlic against N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity and oxidative stress was
      investigated in male Swiss mice. In vivo bone marrow micronucleus test was
      performed to assess the antigenotoxic effect of tomato and garlic. Oxidative
      stress was monitored by estimating the extent of lipid peroxidation and the
      status of the glutathione redox cycle antioxidants. Increased frequency of bone
      marrow micronuclei with enhanced lipid peroxidation was associated with
      compromised antioxidant defenses in MNNG treated animals. Although pretreatment
      with tomato and garlic significantly reduced the frequencies of MNNG-induced bone
      marrow micronuclei, the combination of tomato and garlic exerted a greater
      protective effect. This was associated with modulation of lipid peroxidation as
      well as reduced glutathione (GSH) and the GSH-dependent enzymes glutathione
      peroxidase (GPx) and glutathione-S-transferase (GST). These findings suggest that
      a diet containing even low levels of different naturally occurring compounds is
      effective in exerting antigenotoxic effects by modulating oxidative stress.

PMID- 15733940
TI  - Pitavastatin at low dose activates endothelial nitric oxide synthase through PI3K
      AKT pathway in endothelial cells.
AB  - Pitavastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that
      is used for suppressing cholesterol biosynthesis. Previously, we have reported
      that pitavastatin induces the activation of endothelial nitric oxide synthase
      (eNOS) and increases nitric oxide (NO) production in vascular endothelial cells
      (EC). However, the mechanism of eNOS activation by pitavastatin remains unknown.
      Here, we examined the implications of pitavastatin-induced signaling in eNOS
      phosphorylation in EC. We found that treatment of EC with a low dose of
      pitavastatin induced eNOS phosphorylation at Ser-1177, activated Akt
      phosphorylation at Ser-473 in a time-and dose-dependent manner, and increased NO
      production. These processes were suppressed by the addition of either mevalonic
      acid (MEV) or geranylgeranyl pyrophosphate (GGPP). In addition, northern blot
      analysis revealed that pitavastatin did not increase eNOS mRNA expression level
      in EC. These results suggest that the activation of eNOS with a low dose of
      pitavastatin (0.1 microM) involves phosphoinositide 3-kinase and the Akt pathway
      and produces NO in EC, which is dependent on post-transcriptional regulation.
      This pathway is critical for cellular responses that contribute to EC function.

PMID- 15733941
TI  - Effects of subchronic clozapine administration on serum glucose, cholesterol and
      triglyceride levels, and body weight in male BALB/c mice.
AB  - Atypical antipsychotics, like clozapine, have fewer extrapyramidal side effects
      compared with typical antipsychotics, however, such treatment is associated with
      several adverse metabolic effects such as weight gain, hyperglycemia and
      hyperlipidemia in patients with schizophrenia. In this study, we investigated the
      effects of 30-day clozapine treatment on weight change, and serum fasting
      glucose, cholesterol and triglyceride levels in male BALB/c mice. The results
      demonstrate that 10.0 mg/kg clozapine group gained significantly less weight but
      had higher cholesterol compared with controls and the 2.0 mg/kg clozapine group.
      Our findings indicate the possibility of using mice to study the mechanisms of
      body weight change and lipid dysregulations induced by clozapine.

PMID- 15733943
TI  - Creating an organizational culture for medication safety.
AB  - Medication errors are costly from human, economic, and societal perspectives. All
      patients are vulnerable to the detrimental effects of these errors.
      Recommendations regarding the problem of medication errors include: Prevention of
      error by learning from the nonpunitive reporting of errors and near misses;
      Evaluation of the system for potential causes of error through failure mode and
      effects analysis and encouragement of a questioning attitude; Elimination of
      system problems that increase the risk of error; Recognition that humans are
      fallible and that error will occur even in a perfect system; Minimization of the
      consequences of errors when they do occur. An important goal for healthcare
      organizations should be to create a culture that accepts the imperfection of
      human performance and solicits the assistance of team members in the development
      of safeguards for error prevention. Proposed interventions to prevent medication
      errors can be described by the PATIENT SAFE taxonomy, which includes: Patient
      participation; Adherence to established policy and procedures; Technology use;
      Information accessibility; Education regarding medication safety; Nonpunitive
      approach to reporting of errors and near misses; Teamwork, communication, and
      collaboration; Staffing: adequate number and staffing mix; Administration support
      for the clinical goal of patient safety; Failure mode and effects analysis with
      team member involvement; Environment and equipment to support patient safety

PMID- 15733944
TI  - Reduction of adverse drug events and medication errors in a community hospital
      setting.
AB  - Keys to success in reducing ADEs have included the support of administrative
      leaders through their visibility and emphasis on safety as an organizational
      priority, and financial support for safety projects. Administrative participation
      was also helpful in promoting safety efforts through the reinforcement of
      expectations when progress was sluggish. The use of rapid cycle change provided
      enough early success to serve in motivating staff to push ahead. It allowed staff
      the opportunity to analyze changes, make adjustments, and retest on a slightly
      larger scale. Other key success factors included the motivation of teams through
      continual sharing of progress and success stories; celebrations for achievements
      are held routinely. As an organization, SJMC has shared its success strategies
      with other organizations and promoted networking with other organizations to
      determine what strategies have worked elsewhere. This is helpful as it prevents
      time from being wasted on solutions that have been tried without success. Within
      the OSF Healthcare System, the following phrase has been adopted in regard to
      patient safety, "Safety is like peeling an onion; the more you look, the more you
      find, and each layer makes you cry."

PMID- 15733945
TI  - Use of prescription drugs: rising or declining?
AB  - Prescribing practices are a reflection of health professionals' abilities to
      discriminate among the various choices of drugs and determine the ones that will
      most benefit their patients. As selective as practitioners must be, they cannot
      limit themselves to knowing only those drugs that fit within the dominant
      paradigm of acute care. They must broaden their exposure to incorporate knowledge
      of drugs that permeate clients' lives through media and self-administration.
      Health promotion drug use is just emerging as a prescriptive activity, but it
      will become more significant in the future. Primary and secondary prevention drug
      uses are in flux, and tertiary prevention drug use is likely to overwhelm our
      system, particularly with the baby boom generation, until our society can switch
      its focus to more health promotion and disease prevention. It is imperative that
      health professionals develop shared decision-making capabilities for client
      education and appropriate prescribing. Only when the health care system exhibits
      a true client-provider partnership will the "five rights"-right drug, right dose,
      right route, right time, right client-be accurately applied. With the increasing
      and overwhelming costs of prescription drugs, health practitioners cannot afford
      to sit idle; as professionals and stakeholders, they must engage health policy
      makers and persuade these entities to share their concerns and views, and help
      their clients, the profession, and themselves.

PMID- 15733946
TI  - Strategies for acquiring affordable medications for seniors.
AB  - While Congress continues to debate issues related to Medicaredrug benefits,
      senior citizens grow increasingly frustrated withtheir monthly medication bills.
      Many seniors are unable to affordall of their medications, and therefore find
      that they must choosebetween those that are the most helpful and those that have
      thegreatest potential for severe medical consequences if missed. Op-tions are
      available for helping senior citizens with this financialburden, but many seniors
      are either unaware or unable to availthemselves of the existing programs. Several
      pharmaceutical com-panies have developed programs for the medically needy based
      onincome levels. Generic medications as opposed to trade names re-present
      substantial cost savings. Many pills can be split, thus pro-viding twice the dose
      for half the cost. Some community healthcenters offer access to prescriptions at
      decreased costs through fed-eral programs. This article explores the various
      options availableto senior citizens so that nurses may act as advocates for
      thesepatients.

PMID- 15733947
TI  - Antibiotic resistance.
AB  - Resistance to antibiotics is economically and physiologically costly. Control of
      antibiotic resistance will require aggressive implementation of numerous
      strategies. Ongoing surveillance is needed to monitor known antibiotic types and
      to be able to identify the development of other potential types. Early
      intervention is needed to combat the rising rate of resistance. Persistent use of
      hygiene measures and controlled use of antibiotics will limit the spread of
      antibiotic resistance. Health care providers need to monitor adherence to control
      measures. Hand and environmental control measures remain a critical component of
      staff education activities. Active management of infections with non
      pharmacologic treatments should be promoted. Motivational campaigns will
      reinforce positive infection control behaviors. Consistent surveillance of
      antibiotic use will help fulfill the CDC directive to combat antibiotic
      resistance and keep the population healthy.

PMID- 15733948
TI  - Innovations in antineoplastic therapy.
AB  - Cancer is a complex group of diseases. Many of the current treatment modalities
      available provide limited effectiveness and significant side effects. This
      circumstance creates a challenge for health care providers. There is great need
      for the development of innovative therapies that increase efficacy and decrease
      morbidity. In general, chemotherapeutic agents are unable to distinguish cancer
      cells from normal cells. As a result of therapy, patients may develop significant
      myelosuppression. Patients who are undergoing chemotherapy need to be observed
      for signs of hematologic and nonhematologic toxicities. Patients should be
      advised that periodic blood tests are indicated to monitor for anemia,
      neutropenia, and thrombocytopenia. If myelosuppression develops, measures to
      prevent complications such as bleeding and infection are indicated. Strategies to
      combat fatigue should also be discussed. Understanding of the biology of cancer
      has increased significantly in recent years. As knowledge of the science grows,
      new therapies are developed and clinical trials are initiated to investigate
      feasibility and efficacy of agents. Many of these trials involve agents that
      target specific biologic processes of cancer. While the complexities of cancer
      treatment are prolonging the life expectancy of patients who have the disease,
      patients are presenting with increasing numbers and types of morbidities. Nurses
      need to be aware of the rationale for treatment, mechanism of action of the
      agents administered, and expected toxicities of therapies. With this knowledge,
      symptoms can be identified earlier, life-threatening sequela can possibly be
      averted, and patients and families can be educated about what to expect and how
      to make knowledgeable decisions about treatment options. Enhancing patients'
      knowledge base may also increase their adherence to challenging therapies.

PMID- 15733949
TI  - New developments in antidepressant therapy.
AB  - Depression is an overwhelmingly common problem in the United States. It is not
      only life threatening, but also costly, both personally and financially.
      Following a brief overview of depression, this article presents a variety of
      treatment modalities. Advantages and dis-advantages of each intervention are
      explored along with suggestions for evaluating current and future advances in
      treatment options.

PMID- 15733950
TI  - Multidimensional pharmacologic strategies for diabetes.
AB  - Diabetes is a chronic disease associated with multisystem complications. In
      particular, cardiovascular and renal demise are almost certain in individuals who
      have diabetes, with cardiovascular complications account-ing for over 50% of
      mortality among patients who have type 2 diabetes mellitus. Documented benefits
      of lowering cholesterol, blood pressure, and glucose levels in these patients
      have led to the current emphasis on multidimensional pharmacologic management.
      Table 2 provides a summary of recommendations for managing patients who have type
      2 diabetes.

PMID- 15733951
TI  - Osteoporosis: incidence, prevention, and treatment of the silent killer.
AB  - Osteoporosis is a nationwide health care concern affecting millions of Americans.
      Health care dollars to prevent and treat osteoporosis are needed. Osteoporosis
      related injuries and resulting disabilities, and consequent admissions to
      hospitals, nursing homes, and long-term care facilities is costing billions of
      dollars for care and treatment. Healthy lifestyle choices including vitamin and
      mineral therapy; safe home environments; a diet replete with calcium, vitamin D,
      and protein; weight-bearing and resistance exercises; and fall prevention
      programs for home-bound and hospitalized elders are needed to prevent
      osteoporosis-related fractures and injuries. Nurses must educate the public on
      osteoporosis and osteoporosis-prevention activities. Research in nursing,
      pharmacy, and allied health fields such as physical therapy and nutrition must
      expand to improve understanding of the risks associated with osteoporosis and to
      evaluate health-promotion and disease- prevention activities. Interdisciplinary
      partnerships should be established to study the issues, prevention, and treatment
      modalities of this "silent killer."

PMID- 15733952
TI  - Emerging trends in the management of heart failure: Beta blocker therapy.
AB  - There is overwhelming evidence that beta blocker therapy in the form of
      metoprolol, bisoprolol, and carvedilol can have positive outcomes on morbidity,
      mortality, and quality of life in patients who have been diagnosed with mild to
      severe heart failure. Barring contraindications, beta blockers should be
      considered a cornerstone of therapy for these patients along with ACE inhibitors
      and diuretics. Beta blocking drugs are effective in modifying the cascade of
      events that occur as a result of the neurohormonal response that leads to the
      devastating effects evident during heart failure. Long-term effects of beta
      blockade include an increase in cardiac output, an increase in exercise
      tolerance, a decrease in the number of hospitalizations, and an overall
      improvement in symptoms.

PMID- 15733953
TI  - Update on antiviral agents for HIV and AIDS.
AB  - Drug therapy is a vital component of the care required to promote quality of life
      for individuals who are afflicted with HIV or AIDS. Issues including weight loss
      and gain, heart disease, insulin resistance, and even increased bone metabolism
      must be considered when determining appropriate pharmacologic therapy. New
      complications often arise with new treatments; living longer may not always mean
      living better. However, it is the responsibility of nurses to promote the best
      care possible. Management of appropriate drug therapy and the related
      implications are critical nursing responsibilities in the care of individuals who
      have HIV or AIDS.

PMID- 15733954
TI  - An evaluation of children's metered-dose inhaler technique for asthma
      medications.
AB  - Regardless of the medication delivery system, health care providers need to teach
      accurate medication administration techniques to their patients, educate them
      about the particular nuances of the prescribed delivery system (eg, proper
      storage), and reinforce these issues at each health encounter. A single
      instruction session is not sufficient to maintain appropriate inhaler techniques
      for patients who require continued use. Providing written steps for the
      administration technique is helpful so that the patient can refer to them later
      when using the medication. The National Heart, Lung, and Blood Institute's
      "Practical Guide for the Diagnosis and Management of Asthma" recommends that
      practitioners follow these steps for effective inhaler technique training when
      first prescribing an inhaler: 1. Teach patients the steps and give written
      instruction handouts. 2. Demonstrate how to use the inhaler step-by-step. 3. Ask
      patients to demonstrate how to use the inhaler. Let the patient refer to the
      handout on the first training. Then use the handout asa checklist to assess the
      patient's future technique. 4. Provide feedback to patients about what they did
      right and what they need to improve. Have patients demonstrate their technique
      again, if necessary. The last two steps should be performed (ie, demonstration
      and providing feedback on what patients did right and what they need to improve)
      at every subsequent visit. If the patient makes multiple errors, it is advisable
      to focus on improving one or two key steps at a time. With improvements in drug
      delivery come challenges, necessitating that practitioners stay current with new
      medication administration techniques. Teaching and reinforcing accurate technique
      at each health care encounter are critical to help ensure medication efficacy for
      patients with asthma. Since one fifth of children in the study performed
      incorrect medication technique even after education, checklists of steps for the
      correct use of inhalation devices, such as those provided in this article, should
      be given to patients for home use and for use by clinicians to evaluate patient
      technique at each health encounter.

PMID- 15733955
TI  - The role of surface pigmentation for recognition revealed by contrast reversal in
      faces and Greebles.
AB  - Faces are difficult to recognize when viewed as negatives [Galper (1970).
      Recognition of faces in photographic negative. Psychonomic Science, 19, 207].
      Here we examined the contribution of surface properties to this contrast effect,
      and whether it is modulated by object category. We tested observers in a matching
      task using faces or Greebles, presented with or without pigmentation. When
      stimulus pairs were shown with mismatched contrast (e.g., positive-negative),
      there was a decrement in performance. This decrement was larger when the stimuli
      were shown with pigmentation, and this difference was more pronounced with faces
      than with Greebles. Overall, contrast reversal disrupts the recognition of both
      faces and objects to a greater degree in the presence of pigmentation, suggesting
      that surface properties are important components of the object representation.

PMID- 15733956
TI  - Identification of a protanomalous chimpanzee by molecular genetic and
      electroretinogram analyses.
AB  - We determined the structures of long (L)-wavelength-sensitive and middle (M)
      wavelength-sensitive opsin gene array of 58 male chimpanzees and we investigated
      relative sensitivity to red and green lights by electroretinogram flicker
      photometry. One subject had protanomalous color vision, while others had normal
      color vision. Unlike in humans, a polymorphic difference in the copy number of
      the genes and a polymorphic base substitution at amino acid position 180 were not
      frequently observed in chimpanzees.

PMID- 15733957
TI  - A pulse-step model of accommodation dynamics in the aging eye.
AB  - We have developed a dynamic model of accommodation that combines independent
      phasic-velocity and tonic-position neural signals to control position, velocity
      and acceleration properties of accommodative step responses. Phasic and tonic
      signals were obtained from neural integration of a fixed-height acceleration
      pulse and variable-height velocity-step respectively to control independent
      acceleration and velocity properties of the step response. Duration and amplitude
      of the acceleration-pulse are increased with age to compensate for age-related
      increases of visco-elastic properties of the lens to maintain youthful velocity.
      The model illustrates a neural control strategy that is similar to the classical
      neural control model of step changes by the saccadic and vergence systems.

PMID- 15733958
TI  - Contrast sensitivity of form and motion discrimination during binocular rivalry.
AB  - Binocular rivalry, which is induced by presenting the two eyes with incompatible
      stimuli, results in periods where one eye's stimulus is seen and the other
      stimulus is suppressed. We measured the depth of suppression in two ways, with
      very different results. First, two similar forms were briefly presented to one
      eye: the difference in shapes required to discriminate the forms was
      substantially greater during suppression than during dominance. Second, the two
      forms were made sufficiently different in shape to be easily distinguishable at
      high contrast, and contrast was lowered to find the threshold for discrimination
      of the forms. Contrast sensitivity did not differ between the suppression and
      dominance states. These results were replicated with a motion discrimination
      task: suppression markedly worsened the ability to distinguish increases from
      decreases in speed but did not elevate the minimum contrast required for the same
      task. We interpret the results in terms of steep contrast-response functions in
      visual cortex beyond the primary area.

PMID- 15733959
TI  - Accommodation with and without short-wavelength-sensitive cones and chromatic
      aberration.
AB  - Accommodation was monitored while observers (23) viewed a square-wave grating
      (2.2 cycles/deg; 0.53 contrast) in a Badal optometer. The grating moved
      sinusoidally (0.2 Hz) to provide a stimulus between -1.00 D and -3.00 D during
      trials lasting 40.96 s. There were three illumination conditions: 1.
      Monochromatic 550 nm light to stimulate long-wavelength-sensitive cones (L-cones)
      and medium-wavelength-sensitive cones (M-cones) without chromatic aberration; 2.
      Monochromatic 550 nm light+420 nm light to stimulate long-, medium- and short
      wavelength-sensitive cones (S-cones) with longitudinal chromatic aberration
      (LCA); 3. Monochromatic 550 nm light+420 nm light to stimulate L-, M- and S-cones
      viewed through an achromatizing lens. In the presence of LCA mean dynamic gain
      decreased (p=0.0003; ANOVA) and mean accommodation level was reduced (p=0.001;
      ANOVA). The reduction in gain and increased lag of accommodation in the presence
      of LCA could result from a blue-yellow chromatic signal or from a larger depth-of
      focus.

PMID- 15733960
TI  - Timing sight and sound.
AB  - It has been proposed that there is a perceptual compensation for the difference
      between the speeds of light and sound. We examined this possibility using a range
      of auditory-visual tasks, in which performance depends on the relative timing of
      auditory and visual information, and manipulated viewing distance to test for
      perceptual compensation. We explored auditory-visual integration, cross modal
      causal attributions, and auditory-visual temporal order judgments. We observed
      timing shifts with viewing distance following loudspeaker, but not headphone,
      presentations. We were unable to find reliable evidence of perceptual
      compensation. Our findings suggest that auditory and visual signals of an event
      that reach an observer at the same point in time tend to become perceptually
      bound, even when the sources of those signals could not have occurred together.

PMID- 15733961
TI  - Visual and spatial symptoms in Parkinson's disease.
AB  - The interaction of visual/visuospatial and motor symptoms in Parkinson's disease
      (PD) was investigated by means of a 31-item self-report questionnaire. The
      majority of 81 non-demented patients reported problems on non-motor tasks that
      depended on visual or visuospatial abilities. Over a third reported visual
      hallucinations, double vision and difficulty estimating spatial relations.
      Freezing of gait was associated with visual hallucinations, double vision and
      contrast sensitivity deficits. Visual strategies frequently were employed to
      overcome freezing. The results underscore the importance of investigating visual
      and visuospatial impairments in PD and their relation to motor symptoms, in order
      to help patients develop successful compensatory strategies.

PMID- 15733962
TI  - Near work induced wavefront aberrations in myopia.
AB  - We undertook a detailed analysis of the wavefront aberrations of the eyes of 20
      young progressing myopes (mean age=22 years; mean spherical equivalent=-3.84 D,
      range -1.00 to -7.5 D) and twenty young age matched emmetropes (mean age=23
      years; mean spherical equivalent=-0.00 D, range +0.25 to -0.25 D). A wavefront
      sensor was used to measure the ocular wavefront and a videokeratoscope was used
      to measure corneal topography. The corneal wavefront was subsequently calculated
      and the difference between the corneal and ocular wavefront was derived to give
      the internal wavefront component of the eye. Ocular and corneal wavefronts were
      measured before and after a 2-h reading task. At the baseline measurements, the
      myopes showed greater levels of some high order ocular wavefronts than the
      emmetropes. These differences between the groups became larger following 2 h of
      reading. Ocular higher order wavefront RMS was (baseline RMS: myopes=0.21 microm,
      emmetropes=0.16 microm, difference p=0.05 and after 2 h reading was RMS:
      myopes=0.27 microm, emmetropes=0.17 microm, difference p=0.02). The differences
      between the groups are primarily due to changes in the corneal wavefront
      associated with a narrower lid aperture during reading for the myopes. These
      differences are enhanced by longer periods spent reading, larger pupils and
      consequently low light levels. We suggest lid induced corneal changes caused by
      reading in downgaze provides a theoretical framework that could explain the known
      features of myopia development. The inherited characteristics of facial and lid
      anatomy would provide a mechanism for a genetic component in the genesis of
      myopia.

PMID- 15733963
TI  - Attention-based motion perception and motion adaptation: what does attention
      contribute?
AB  - Attention-based motion perception refers to the phenomenon that a stimulus with
      ambiguous motion energy can be seen to move in a direction that is under
      attentive control of the observer. The role of attention is obvious when the
      stimulus is ambiguous: it makes the stimulus move in one direction. The goal of
      the current experiment is to investigate what the contribution of attention under
      attentive tracking conditions actually is, especially while viewing-time
      progresses. We had our observers look at a circular array of four evenly spaced
      discs whose motion direction was biased in the clockwise direction. Observers
      either viewed the stimulus moving around a circular path passively or actively.
      In the latter case they attentively tracked one of the discs. The observer's task
      was to indicate the perceived direction of motion. As time progresses, this kind
      of stimulus will undergo spontaneous motion direction reversals. We analyzed the
      time course of the reversals and show that actively attentive tracking the
      stimulus massively delays the reversal time. These results suggest that attention
      can temporarily overrule lower level adaptation.

PMID- 15733965
TI  - Effects of attention on motion repulsion.
AB  - Motion repulsion involves interaction between two directions of motion. Since
      attention is known to bias interactions among different stimuli, we investigated
      the effect of attentional tasks on motion repulsion. We used two overlapping sets
      of random dots moving in different directions. When subjects had to detect a
      small speed-change or luminance change for dots along one direction, the
      repulsive influence from the other direction was significantly reduced compared
      with the control case without attentional tasks. However, when the speed-change
      could occur to either direction such that subjects had to attend both directions
      to detect the change, motion repulsion was not different from the control. A
      further experiment showed that decreasing the difficulty of the attentional task
      resulted in the disappearance of the attentional effect in the case of attention
      to one direction. Finally, over a wide range of contrasts for the unattended
      direction, attention reduced repulsion measured with the attended direction.
      These results are consistent with the physiological finding that strong attention
      to one direction of motion reduces inhibitory effects from the other direction.

PMID- 15733964
TI  - Vernier acuity for stereodisparate objects and ocular prevalence.
AB  - QUESTION: How precisely can objects, located in different depth planes, be
      aligned to the same visual direction? METHODS: Twenty normal observers were
      presented with vertical Vernier lines at various stereodisparities. They had to
      judge whether the lower, anterior line was located on the right- or left-hand
      side of the upper, posterior line. RESULTS: Over a stereodisparity range from
      zero to 62'', the threshold for detecting a lateral offset between the Vernier
      lines remained at the "hyperacuity" level of about 7''. With larger
      stereodisparities, the threshold increased about fourfold, probably due to a
      mutual, partial suppression of the position signals from the right and left eyes.
      The reference point from which the observers judged the relative visual
      directions between stereodisparate objects was not located midway between the
      eyes; rather, it was often decentred towards the right or the left eye, meaning
      that the observers had an "ocular prevalence". Their ocular prevalence was,
      however, not strong enough to have an effect on the Vernier acuity for
      stereodisparate objects. (Under pathological conditions like strabismic
      amblyopia, one should expect a 100% prevalence of the good eye, implying that the
      Vernier acuity reaches the monocular level, irrespective of any depth difference
      between objects.) CONCLUSION: Vernier acuity decreases with increasing
      stereodisparity. Ocular prevalence, occurring frequently among persons with
      normal eyes, has no effect on Vernier acuity for stereodisparate objects. For a
      typical everyday viewing condition, the reduced Vernier acuity beyond a
      stereodisparity of 62'' means that, from a viewing distance of 40 cm, precision
      mechanics have to guide their instrument as close as 0.4mm to a workpiece, until
      they can utilise their best position acuity.

PMID- 15733966
TI  - Transient reduction of the ocular perfusion pressure and the oscillatory
      potentials of the ERG.
AB  - PURPOSE: To evaluate the changes of the Oscillatory Potentials (OPs) of
      Electroretinogram (ERG) caused by short-term hypertension in human subjects, and
      their relationship with ocular perfusion pressure (OPP). METHODS: Suction cup
      technique in 12 normal volunteers with OPs simultaneously recording. RESULTS:
      Scotopic and photopic OPs were altered during OPP drop. Scotopic OPs showed more
      sensitiveness, with higher reduction (from 21% to 47%), when compared to the
      basal value, than in photopic recordings (from 14% to 34%). In both conditions,
      the relationship between OPP and OPs presented a steady amplitude before the
      trough after the +30 step, and rapid recovery after OPP normalisation. ANOVA and
      correlation analysis confirmed the data. CONCLUSION: The ERG OPs seemed to
      reflect the OPP modification. The features of OPs amplitudes suggest involvement
      of the retinal autoregulation mechanism and support development for further
      clinical studies.

PMID- 15733967
TI  - Characterization of two novel mutations of the antithrombin gene observed in
      Japanese thrombophilic patients.
AB  - We investigated the molecular basis of reduced functional levels of antithrombin
      (AT) in two individuals suffering from thromboembolic events. In each case direct
      sequencing of amplified DNA revealed 13,260-13,262 del in one patient and 2511C>A
      in the other patient, predicting a heterozygous E381del and P16H, respectively.
      Both patients had no 20210A allele and factor V Leiden mutation. To understand
      the molecular mechanism responsible for antithrombin deficiency, stable
      expression experiments were performed using HEK293 cells transfected with the
      expression vector containing the wild-type or the mutated recombinant cDNA. In
      these experiments, the media levels of the two mutated antithrombins were the
      same as that of wild type, but the specific activity of the E381del mutant
      decreased significantly compared with that of wild type. These results showed
      that the E381del mutation was responsible for type II deficiency, whereas the
      other mutation, P16H, did not produce any definite abnormality which could
      contribute to antithrombin deficiency.

PMID- 15733968
TI  - Effects of hormone replacement therapy on blood coagulation and fibrinolysis in
      hypertensive and normotensive postmenopausal women.
AB  - INTRODUCTION: Hypertension and estrogens are both prothrombotic. We investigated
      the effect of 12-month hormone replacement therapy (HRT) on hemostatic factors in
      mild to moderate essential hypertensive and normotensive postmenopausal women.
      MATERIALS AND METHODS: A group of 38 hypertensive and 32 normotensive
      postmenopausal women received HRT (conjugated equine estrogen 0.625 mg plus
      medroxyprogesterone acetate 2.5 mg daily) for 12 months, and 19 hypertensive and
      15 normotensive postmenopausal women did not. All hypertensive women had been
      administered antihypetensive drugs before the start of the study. Hemostatic
      factors, i.e., fibrogen, antithrombin, protein C activity, plasminogen activator
      inhibitor-1, D-dimer, and plasminogen, were measured in plasma of all women
      before, and 6 and 12 months after the start of study. RESULT: The antithrombin
      levels of the hypertensive and normotensive women who received HRT had decreased
      at 6 (both P<0.001) and 12 months (P<0.001 and P<0.01) and their D-dimer at 12
      months (both P<0.05) and plasminogen levels at 6 (both P<0.001) and 12 months
      (both P<0.001) has increased, but other hemostatic factors were unchanged. There
      were no changes in hemostatic factors in either control group. CONCLUSION: HRT
      for 12 months activated blood coagulation and fibrinolysis in both hypertensive
      and normotensive postmenopausal women. Administration of CEE plus MPA therapy to
      hypertensive or normotensive postmenopausal women may be related to the
      thromboembolic events.

PMID- 15733969
TI  - Thromboxane and prostacyclin biosynthesis in patients with acute spontaneous
      intracerebral hemorrhage.
AB  - OBJECTIVE: Elevated levels of 11-dehydrothromboxane B2 (11-dehydro-TXB2) excreted
      in urine have been observed in acute ischemic stroke. This marker of platelet
      activation has not been investigated in patients with acute spontaneous
      intracerebral hemorrhage (ICH). METHODS: We examined 43 patients with spontaneous
      ICH and 23 controls. Urinary excretion rates of 11-dehydro-TXB2, 2,3-dinor
      thromboxane B2 (2,3 dinor-TXB2) and 2,3-dinor-6-ketoprostaglandin F(1alpha) (2,3
      dinor-PGF(1alpha)) during the first week and at 3 months after ICH were compared
      between patients who had or had not used aspirin and controls. RESULTS: On
      admission, ICH patients without aspirin use had significantly higher urinary
      levels of 11-dehydro-TXB2 (p<0.001), 2,3-dinor-TXB2 (p<0.001) and 2,3-dinor
      PGF(1alpha) (p=0.019) than controls. Aspirin users had significantly lower
      urinary levels of these metabolites than nonusers. The metabolite levels of
      aspirin users on admission did not significantly differ from those of controls.
      The differences between aspirin users and nonusers leveled off during the
      following 3-5 days, however, as the blocking effect of aspirin on the production
      of TXA2 and PGI2 ceased. Three months after ICH, the metabolite excretion levels
      in all the patients were similar to those in nonusers of aspirin on admission. On
      admission, aspirin users had longer bleeding times (p=0.032) than nonusers, but
      aspirin use did not associate with impaired recovery or hematoma enlargement.
      CONCLUSIONS: Urinary excretion levels of 11-dehydro-TXB2, 2,3-dinor-TXB2 and 2,3
      dinor-PGF1alpha were higher in patients with acute ICH than in controls. The
      levels in aspirin users were equally low as in controls but rose to the levels of
      the other patients within a few days. The metabolite levels remained high 3
      months after ICH in all patients. Prior use of aspirin did not seem to cause
      hematoma enlargement.

PMID- 15733970
TI  - eNOS genotype is without effect on circulating nitrite/nitrate level in healthy
      male population.
AB  - INTRODUCTION: Nitric oxide (NO) plays an important role in the regulation of the
      cardiovascular system. It is produced by endothelial nitric oxide synthase
      (eNOS), which exhibits genetic polymorphisms. Although the clinically relevant
      polymorphism T(+IhI-786)C reduces eNOS-promoter activity, it is not clear whether
      circulating nitrite/nitrate (NOx) are affected by this polymorphism. MATERIALS
      AND METHODS: We addressed this issue by studying a homogeneous group of 200
      healthy subjects (males, Caucasians, nonsmokers, 18+IBM-56 years of age, and not
      taking any medication). Genotypes were determined by restriction fragment length
      polymorphism and circulating NOx were determined by chemiluminescence. RESULTS:
      We found nonsignificant effects of the T(+IhI-786)C polymorphism on circulating
      NOx (mean+ALE-S.D.=52.2+ALE-21.4, 49.0+ALE-17.8, and 45.9+ALE-16.8 +A7w-mol/L for
      genotypes +IBw-TT,+IB0 +IBw-TC,+IB0 and +IBw-CC,+IB0 respectively) and on total
      plasma cholesterol concentrations (both P>.05). No correlation was found between
      circulating NOx and total plasma cholesterol concentrations (P>.05). CONCLUSIONS:
      Our study provides strong evidence that the T(+IhI-786)C polymorphism does not
      affect plasma NOx concentrations, which are believed to reflect endogenous
      production of NO. Therefore, our results suggest that this polymorphism does not
      affect endogenous NO production.

PMID- 15733971
TI  - Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the
      quantitative determination of D-dimer.
AB  - The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA),
      a rapid fully automated assay, could be used as an initial screening test in the
      diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive
      symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients,
      21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients)
      or suspected for both complications (n=8) were tested with this D-dimer assay
      with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary
      embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest
      risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by
      spiral-computed tomography of the pulmonary arteries or compression
      ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas
      DVT was confirmed in 17.7% of the patients. The optimal cut-off value for
      exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity
      and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95%
      CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient
      with PE were missed using D-Dimer PLUS; both cases were outpatients. In
      conclusion, this assay appears to be safe when implemented in an algorithm based
      on clinical assessment, D-dimer concentration, and radiological diagnostic
      techniques to stratify the risk for PE or DVT. However, higher sensitivities and
      negative predictive values were claimed in the scarce published reports for the D
      Dimer PLUS assay than found in this study.

PMID- 15733972
TI  - Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy
      related hypertension and severe intrauterine growth retardation.
AB  - OBJECTIVE: Recently, acquired as well as genetic prothrombotic factors are
      associated with thrombotic events. These factors have also been related to
      conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome
      and severe intrauterine growth restriction (IUGR). The aim of this study was to
      determine whether elevated factor VIII levels are associated with uteroplacental
      insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced
      hypertension and intrauterine growth retardation. METHODS: Plasma samples of 75
      women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome,
      pregnancy induced hypertension or intrauterine growth restriction were tested for
      factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory
      results were compared to factor VIII:C levels found in a healthy control group of
      272 women. RESULTS: Mean factor VIII:C levels were similar at 123 IU/dl in both
      the patient group and the controls. In a logistic regression model, after
      adjusting for age and blood group, no effect of factor VIII:C levels on the risk
      of pregnancy complications was observed, with the exception of IUGR with (OR 2.9,
      CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). CONCLUSION: If the
      elevated level of factor VIII would be the sole factor responsible for the
      increased risk observed, one would expect to find an effect of blood group on
      risk as well (blood group being an important determinant of FVIII:C). While no
      such effect could be shown a causal relationship between elevated levels of
      factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia,
      HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

PMID- 15733973
TI  - TNF-alpha -308G/A and IL-6 -174 G/C polymorphisms in the Turkish pediatric stroke
      patients.
AB  - INTRODUCTION: Introduction: Stroke is an important cause of mortality and
      morbidity in the pediatric age group. There is increasing evidence on the role of
      proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) in the occurrence and outcome of stroke. These proinflammatory
      cytokines carry functional polymorphisms (IL-6 -174 G/C and TNF-alpha -308 G/A)
      in their promoter regions, affecting their transcription rate and plasma cytokine
      levels. The aim of this study was to investigate the association of these
      polymorphisms with the occurrence of stroke in the Turkish pediatric stroke
      patients. MATERIAL AND METHODS: Eighty six arterial stroke patients (aged between
      0 and 14) and 83 healthy unrelated adult controls without personal or family
      history of stroke were investigated by PCR and restriction endonuclease analysis
      for IL-6 -174 G/C and TNF-alpha -308 G/A polymorphisms. RESULTS: The allele
      distribution, allele frequencies, and combined distribution of genotypes for both
      polymorphisms did not differ significantly between control and patient groups.
      CONCLUSIONS: The two polymorphisms did not associate with the occurrence of
      stroke in our study group.

PMID- 15733974
TI  - Atypical onset of antiphospholipid syndrome in pregnancy: a case report.
AB  - BACKGROUND: We present a case of an atypical onset of antiphospholipid syndrome
      (APS). CASE: A woman in her 15th week gestation had a thrombosis of an unknown
      cerebral cavernoma, which was successfully removed. Twenty-six days after, she
      was admitted for a severe pain in right hypochondrium and a second class HELLP
      syndrome was diagnosed. Two days after, she had a fetal loss. After 1 month,
      laboratory tests revealed high level of antiphospholipid antibodies. At the same
      time, she developed a spontaneous thrombosis at her right arm. After 6 weeks,
      antiphospholipid antibodies, tested again, result positive. CONCLUSION:
      Antiphospholipid antibodies often cause pregnancy complications, but, to our
      knowledge, this is the first report of an association of antiphospholipid
      antibodies, with cerebral cavernoma thrombosis and early onset HELLP syndrome.

PMID- 15733975
TI  - The intracellular action of sphingosine 1-phosphate in GPVI-mediated Ca2+
      mobilization in platelets.
AB  - We analyzed the intracellular action of sphingosine 1-phosphate (Sph-1-P), formed
      from sphingosine (Sph) by sphingosine kinase (SPHK), in platelets. When
      sphingosine kinase activity was inhibited by N,N-dimethylsphingosine (DMS), Ca2+
      mobilization induced by convulxin, an agonist of the collagen receptor
      glycoprotein VI (GPVI), was moderately but specifically abolished; that induced
      via G protein-coupled receptors was not affected. Under the same conditions,
      however, tyrosine phosphorylation of Syk and phospholipase Cgamma2, which is
      essential for the GPVI-mediated signaling, was not inhibited. Sphingosine kinase
      activity of the platelet membrane fraction increased specifically upon
      stimulation with convulxin or collagen. Our results suggest that intracellular
      sphingosine 1-phosphate is related to Ca2+ mobilization in GPVI-mediated
      signaling pathways.

PMID- 15733976
TI  - Effects of TNF-alpha and curcumin on the expression of thrombomodulin and
      endothelial protein C receptor in human endothelial cells.
AB  - The objective of this study was to elucidate the effects of tumor necrosis factor
      alpha (TNF-alpha) on the expression of thrombomodulin (TM) and endothelial
      protein C receptor (EPCR) in human endothelial cells as well as the effect of
      curcumin, a spice and coloring food compound, as a potential therapeutic agent.
      Human umbilical vein endothelial cells (HUVECs) treated with TNF-alpha (2.0
      ng/ml) showed reduced TM mRNA levels by 80%, 97%, 94%, and 97% at 3, 6, 12, and
      24 h, respectively (P<0.05), by real-time PCR analysis. Dose-dependent study
      showed that TM mRNA levels of HUVECs were decreased by 86%, 89%, 91%, and 94%
      after treatment of TNF-alpha (0, 0.25, 0.5, 1, and 2 ng/ml) for 6 h, respectively
      (P<0.05). TM protein levels in HUVECs were significantly reduced by 69% in TNF
      alpha-treated cells as compared to controls (P<0.05) by Western blot analysis.
      Secreted protein and activity of TM of HUVEC cultures were also significantly
      reduced in TNF-alpha-treated cells. In addition, EPCR mRNA levels of HUVECs were
      significantly reduced in TNF-alpha-treated group as compared to controls
      (P<0.05). Furthermore, these effects were observed in other types of endothelial
      cells from human coronary arteries, lung, and skin. Curcumin effectively blocked
      these effects of TNF-alpha on downregulation of TM and EPCR. These data
      demonstrate that TNF-alpha significantly decreases expression of TM and EPCR at
      both mRNA and protein levels in several human endothelial cells. Curcumin can
      effectively block TNF-alpha-induced endothelial dysfunction. This study suggests
      a new molecular mechanism of inflammation-induced thrombosis and a new
      therapeutic strategy to prevent this clinical problem.

PMID- 15733977
TI  - Heparin compromises streptokinase-induced arterial patency in rabbits.
AB  - INTRODUCTION: Little is known with regard to efficacy of heparin as an adjunct to
      fibrinolytics under conditions of severe vascular damage. In this study, we
      compared the effects of unfractionated heparin (UH), low-molecular weight heparin
      (LMWH), and recombinant desulfohirudin (HIR) in combination with streptokinase
      (SK) in such settings. MATERIALS AND METHODS: We used an established rabbit
      model, in which thrombosis, critical stenosis, and vascular wall damage were
      introduced to a segment of the abdominal aorta and the effects of the respective
      therapies were assessed by time to patency (TTP in minutes), cumulative patency
      (CP (%)), lysis of original clot (CL (%)), and net clot accretion (NCA (%)).
      Treatments were administered over 90 min at the following doses: SK: 33,000 U/kg,
      UH: 125-250 U/kg, LMWH: 1.25-2.5 mg/kg, HIR: 0.25-0.55 mg/kg. RESULTS:
      Unexpectedly, UH and LMWH had a paradoxical and detrimental effect on SK-mediated
      recanalization as measured by both TTP and CP. Thus, administration of SK vs.
      SK+UH or SK+LMWH resulted in TTP values of 43+/-8 min vs. 70+/-11 min (p<0.05)
      and 67+/-12 min. (p<0.08), respectively. For CP, the corresponding values were
      21+/-7%, 0.5+/-0.3% and 9+/-8%. This delay in vessel recanalization occurred
      despite excessive systemic anticoagulation (activated partial thromboplastin time
      (aPTT) and thrombin clotting time (TCT) ratios >6 and >34, respectively). Of
      interest, both heparinoids completely inhibited SK-induced fibrinogen consumption
      (FC). In contrast, recombinant desulfohirudin (HIR) shortened SK-induced TTP
      (4.97+/-0.81 min) without preserving fibrinogen. CONCLUSIONS: Our findings
      suggest that caution needs to be exercised, when using the combination of SK and
      heparinoids for the treatment of arterial thrombosis under conditions of severe
      vascular damage and stenosis.

PMID- 15733978
TI  - Dipyridamole enhances tissue plasminogen activator release by brain capillary
      endothelial cells.

PMID- 15733979
TI  - Predisposing factors in patients with early-onset cerebral vein thrombosis.

PMID- 15733980
TI  - Ocular higher-order aberrations in eyes with supernormal vision.
AB  - PURPOSE: To quantify ocular higher-order aberrations (HOAs) in eyes with
      supernormal vision, that is, natural uncorrected visual acuity (UCVA) > or =
      20/15, to analyze the correlation between ocular HOAs and age in these eyes, and
      to investigate the correlation of HOAs between right and left eyes. DESIGN:
      Observational case series. METHODS: Ocular HOAs were examined across a naturally
      dilated pupil with a diameter > or = 6.0 mm in 70 eyes of 35 subjects with > or =
      20/15 UCVA (mean age 24.3 years +/- 7.7 [SD]) using the Nidek OPD scan wavefront
      aberrometer. Root-mean-square (RMS) values of HOA, total spherical aberration
      (TSA), total coma (TC), and total trefoil (TT) were analyzed. Correlation
      analysis was performed to assess the association between ocular HOAs and age and
      the correlation of HOAs between right and left eyes. RESULTS: Mean RMS values
      were 0.334 +/- 0.192 microm for HOA, 0.110 +/- 0.077 microm for TSA, 0.136 +/-
      0.081 microm for TC, and 0.268 +/- 0.220 microm for TT. There were no significant
      differences in the mean values of HOA, TSA, TC, and TT between right and left
      eyes. The Pearson correlation coefficient between right and left eyes for TSA was
      0.764 (P<.0001). No significant correlation was found between right and left eyes
      for HOA, TC, and TT. No significant correlation was found between each of the
      ocular aberrations and age. CONCLUSIONS: The amount of ocular HOAs in eyes with
      natural supernormal vision is not negligible, and is comparable to the reported
      amount of HOAs in myopic eyes.

PMID- 15733981
TI  - The treatment of primary acquired melanosis (PAM) with atypia by topical
      Mitomycin C.
AB  - PURPOSE: To report our results of 12 consecutive patients with conjunctival
      primary acquired melanosis (PAM) with atypia who were treated by topical
      Mitomycin C (MMC). DESIGN: Retrospective interventional consecutive case series.
      METHODS: Twelve patients with PAM with atypia in one of their eyes who were
      treated by topical chemotherapy with MMC were included in this case study. Eyes
      with histologically proven PAM with atypia were treated by two to five courses of
      0.04% (0.4 mg/ml) MMC four times a day. Each course lasted 2 continuous weeks.
      Follow-up was conducted on patients for control of local disease, side effects,
      and visual acuity in the treated eye. RESULTS: In all patients, there was
      complete or partial response to treatment. In four patients, the pigmentation
      disappeared, whereas in eight patients, some remnants of the pigmentation
      remained. In seven of these eight patients, the remnants of the pigmentation were
      stable during the follow-up period of 4 months to 9 years, whereas one in whom re
      growth of the PAM was noticed was successfully treated again by topical MMC. No
      patients lost visual acuity at the end of the follow-up. All side effects of the
      local chemotherapy were resolved after cessation of the treatment. CONCLUSIONS:
      Topical MMC chemotherapy is a good alternative to surgical excision and
      cryotherapy in treating conjunctival PAM with atypia.

PMID- 15733982
TI  - Primary placement of a hydroxyapatite-coated sleeve in bioceramic orbital
      implants.
AB  - PURPOSE: To study a new surgical option of primary placement of a hydroxyapatite
      coated sleeve into the Bioceramic implant during enucleation or evisceration.
      DESIGN: Retrospective, observational case series. METHODS: A standard enucleation
      or evisceration was performed, followed by the preplacement of a hydroxyapatite
      coated sleeve into the Bioceramic implant. Care must be taken to ensure the
      sleeve has been positioned centrally when the implant is put inside the orbital
      socket. Complications such as sleeve exposure, Bioceramic implant exposure, and
      infection were closely observed. RESULTS: Twenty-seven patients were treated in
      above fashion with five enucleation and 22 evisceration procedures. Five of the
      sleeves have exposed spontaneously during 1 to 4 months after original surgery.
      They had no further complication, except for one sleeve around which there were
      visible Bioceramic spicules attributable to long-term corticosteroid usage. The
      remaining 22 sleeves that did not spontaneously expose pursued secondary exposure
      of the sleeve and peg insertion by the conjunctival cutdown procedure 3 months
      postoperatively. One sleeve was medially positioned far away from the implant
      center. Re-insertion of new sleeve and peg was scheduled 2 weeks later. One
      additional sleeve was obliquely positioned after conjunctival cutdown procedure.
      Fortunately, all 27 patients were successfully fitted with a peg-coupled
      prosthesis with good motility. CONCLUSIONS: Primary placement of a hydroxyapatite
      coated sleeve into the Bioceramic implants has several advantages, including high
      patient acceptance, technical simplicity, and an office-based conjunctival
      cutdown pegging procedure. By avoiding the expense of postoperative imaging
      studies and additional prosthetic modification, a more rapid and efficient
      rehabilitation is possible.

PMID- 15733984
TI  - Optic disk ovality as an index of tilt and its relationship to myopia and
      perimetry.
AB  - PURPOSE: To examine the association of optic disk ovality with myopic refractive
      error, axial length, and the visual field. DESIGN: Prospective observational case
      series. METHODS: The study included 150 randomly recruited male subjects with
      myopia. In all cases, one eye was randomly selected, and subjective refraction,
      slit-lamp examination, applanation tonometry, gonioscopy, A-scan ultrasonography,
      funduscopy, and color optic disk stereo photography were performed. Disk ovality
      was assessed using the ratio of minimum to maximum disk diameter (index of tilt).
      A ratio of < or = 0.8 was considered as significant disk tilt. Visual fields were
      tested using static automated threshold perimetry with two methods of optical
      correction: trial lenses and contact lenses. RESULTS: Of the total sample, 137
      subjects completed the study. Mean age was 21.2 +/- 1.1 year, and mean spherical
      equivalent was -6.36 +/- 3.56 diopters. Mean ovality ratio was 0.83 +/- 0.09; 55
      subjects (40.2%) had significant tilted optic disks. Greater optic disk ovality
      (tilt) correlated with greater myopia (P = .009) and longer axial length (P =
      .009); 95.6% of subjects had normal visual fields with both methods of optical
      correction. Using multiple linear regression analysis, greater tilt was
      independently related to a higher mean defect on testing with trial lenses (P <
      .01). CONCLUSIONS: Increased optic disk tilt was associated with higher myopia
      and reduced sensitivity on field testing. These factors are important in the
      assessment of glaucoma in patients with myopia.

PMID- 15733985
TI  - The application of a new continuous functional visual acuity measurement system
      in dry eye syndromes.
AB  - PURPOSE: To evaluate the efficacy of a new continuous functional visual acuity
      measurement (FVAM) system for the assessment of dry eye patients. DESIGN:
      Prospective comparative study. METHODS: Monocular recognition acuity measured
      continuously by the FVAM system during a 30-second blink-free period was defined
      as functional visual acuity (FVA). Examinations using the FVAM system were
      conducted in 35 eyes of 20 healthy controls and 19 eyes of 13 dry eye patients.
      Tear function examinations including the Schirmer test, tear film break-up time,
      and fluorescein and Rose Bengal staining were performed in all subjects.
      Functional visual acuity and tear functions were also examined before and after
      insertion of punctum plugs in dry eye patients. Functional visual acuity results
      at 10, 20, and 30 seconds were compared. RESULTS: Functional visual acuity in dry
      eyes were significantly lower than control subjects at all time points (P < .05).
      Functional visual acuity after punctum plugs insertion improved significantly at
      all time points (P < .05). CONCLUSIONS: FVAM system seemed not only to be an
      effective tool in the assessment of dynamic visual acuity changes in dry eye and
      normal subjects but in evaluating the outcome of management of dry eye disease by
      punctum plugs.

PMID- 15733986
TI  - Visual prognosis of amblyopia associated with myelinated retinal nerve fibers.
AB  - PURPOSE: To investigate the visual prognosis of amblyopia associated with
      anisomyopia and myelinated nerve fibers. DESIGN: Retrospective noncomparative
      case series. METHODS: Twelve children with amblyopia associated with anisomyopia
      and myelinated nerve fibers were treated with spectacle correction after
      cycloplegic refraction and occlusion therapy for amblyopia. Their visual acuity
      was measured at each visit to the clinic. The patients were divided into three
      groups according to their final visual acuity, and statistical analyses were
      performed to evaluate the differences among these groups in terms of the initial
      age, spherical equivalent, anisometropia, the area of myelination, final age, and
      follow-up period. RESULTS: The mean refractive error of the 12 children in
      spherical equivalents was -8.16 diopters (range -1.50 to approximately -13.00
      diopters). The mean age at the initiation of therapy was 4.2 years (range 2.1 to
      8.6) and the mean follow-up period was 2.6 years (range 0.5 to 5.1). After the
      occlusion treatment, visual acuity improved to 20/30 in four patients, and to
      20/60 in one patient. In the remaining six patients, visual acuity remained at
      20/200 or worse. The amount of anisometropia and the area of myelination were
      significantly different between the group with a final visual acuity of 20/40 or
      better and the group with a final visual acuity of worse than 20/200. CONCLUSION:
      The visual acuity of about one third of the amblyopes with myelinated nerve
      fibers improved to 20/30. The prognostic factors for the visual improvement were
      the amount of anisometropia and the area of myelination.

PMID- 15733983
TI  - The effect of autologous serum eyedrops in the treatment of severe dry eye
      disease: a prospective randomized case-control study.
AB  - PURPOSE: To evaluate the effectiveness of the autologous serum eyedrops in the
      treatment of severe dry eye patients. DESIGN: Prospective randomized case-control
      study. METHODS: Thirty-seven eyes of twenty severe dry eye patients without
      punctal occlusion were enrolled in this study. After 2 weeks of washout, they
      were randomly assigned to two groups. Group A patients used only preservative
      free artificial tears, and group S patients used only autologous serum eyedrops.
      We evaluated the results of Schirmer test, fluorescein and rose bengal staining
      scores, tear film breakup time (BUT), and subjective symptom scores before and 2
      weeks after treatment. RESULTS: Mean BUT and fluorescein and rose bengal staining
      scores, as well as subjective symptom scores, showed significant improvement in
      the patients assigned to autologous serum eyedrops compared with subjects
      assigned to preservative-free artificial tears after 2 weeks of treatment.
      CONCLUSIONS: Autologous serum eyedrops were found effective in the treatment of
      severe dry eye disease, as evidenced by improvement of tear stability and ocular
      surface vital staining scores.

PMID- 15733987
TI  - Alpha-tocopherol in plasma, red blood cells and lenses with and without cataract.
AB  - PURPOSE: To compare levels of alpha-tocopherol in human lenses with cataract to
      clear human lenses and to determine associations between levels of alpha
      tocopherol in plasma, red blood cells, and human lenses with cataract. DESIGN:
      Cross-sectional study. METHODS: Concentrations of alpha-tocopherol were measured
      by high-performance liquid chromatography in blood and in human lenses with and
      without cataract. Lenses were obtained during cataract surgery and from a
      regional eye bank. Peripheral alpha-tocopherol status in patients was assessed as
      plasma alpha-tocopherol (total and corrected for low-density lipoproteins) and as
      red blood cell bound alpha-tocopherol. Data (mean +/- standard error of the mean)
      are expressed as microM alpha-tocopherol/g lens protein, microM alpha
      tocopherol/l plasma, microM alpha-tocopherol/g low-density lipoproteins, and
      microM alpha-tocopherol/T red blood cells. RESULTS: Concentrations of alpha
      tocopherol were measured in 27 lenses of cataract patients, 8 cadaver lenses with
      cataract and in 14 clear cadaver lenses. The concentration of alpha-tocopherol
      was significantly higher in cataract than in control cadaver lenses (0.49 +/-
      0.04 vs 0.35 +/- 0.03, P < .05). The difference between alpha-tocopherol in
      lenses of cataract patients and control cadaver lenses was even higher (0.7 +/-
      0.1 vs 0.35 +/- 0.03, P < .01). No significant correlation was observed between
      plasma alpha-tocopherol or red blood cell bound alpha-tocopherol and lens alpha
      tocopherol in patients. CONCLUSIONS: Serum and red blood cell levels of alpha
      tocopherol may not reflect the alpha-tocopherol status of the lens itself and
      therefore may not be clinically relevant markers for cataract risk. Mechanisms
      leading to increased levels of alpha-tocopherol in cataract lenses need to be
      explored in future research.

PMID- 15733988
TI  - Vision-related quality of life in patients suffering from age-related macular
      degeneration.
AB  - PURPOSE: To evaluate the relative impact of best and worst eye on vision-related
      quality of life in patients suffering from age-related macular degeneration
      (AMD). DESIGN: Quality of life and visual acuity data were collected at baseline
      during a randomized clinical trial. METHODS:  SETTING: Multicenter (11 centers),
      international study. PATIENTS: One hundred fourteen patients with a diagnosis of
      exudative AMD and primary or recurrent subfoveal neovascular membrane (greatest
      linear dimension of lesion < or =5400 microm; > or =50% of the total lesion was
      choroidal neovascularization (CNV); classic component of the total CNV > or = 1.0
      mm(2)). All patients were over age 50 years, of any race, either sex.
      INTERVENTION OR OBSERVATION PROCEDURE: NEI-VFQ-39 questionnaire administered to
      patients at home by trained telephone interviewers. MAIN OUTCOME MEASURES: ETDRS
      visual acuity (VA) was measured in both eyes separately. Vision-related quality
      of life (QoL) was assessed using the NEI-VFQ-39. An analysis of variance was
      performed on the NEI-VFQ scores, including best eye VA (VA > 20/40 vs VA < or =
      20/40), worst eye VA (VA > 20/200 vs VA < or = 20/200), and the interaction
      between the two as independent variables. RESULTS: Best eye VA was 0.34 on
      average, with VA > 20/40 in 43.0% of patients. Worst eye VA was 0.85 on average,
      with VA > 20/200 in 32.5% of patients. VA was not linked to general health and
      ocular pain scores. General Vision, Near Activities, Distance Vision, Driving,
      Mental Health, Role Difficulties, Dependency, Peripheral Vision, and the Global
      NEI-VFQ scores were affected by both best eye VA and worst eye VA. CONCLUSION: In
      the study sample, worst eye VA (< or =20/200) and best eye VA (< or =20/40)
      contributed independently to vision-related QoL. These results suggest that
      preserving a minimal visual acuity in the worst eye may contribute to vision
      related quality of life.

PMID- 15733989
TI  - Photoreceptor layer features in eyes with closed macular holes: optical coherence
      tomography findings and correlation with visual outcomes.
AB  - PURPOSE: Study correlation between optical coherence tomography (OCT) findings
      and visual acuity (VA) outcomes after successful macular hole surgery (MHS).
      DESIGN: Retrospective cross-sectional study. METHODS: Postoperative OCT scans
      were analyzed in 34 eyes of 30 patients. Raw files of horizontal and vertical OCT
      scans were exported to Adobe Photoshop 7.0. Measured parameters included central
      foveal thickness, photoreceptor thickness, photoreceptor reflectivity, and
      relative reflectivity of photoreceptor to retinal pigment epithelium in the
      foveal area. Foveal configuration was subjectively graded. RESULTS: OCT scans
      were obtained at a median of 2 years (1 month to 10 years) postoperatively. The
      median visual acuity was 20/80 (20/50 to 8/200) preoperatively and 20/50 (20/20
      to 5/200) postoperatively. The median foveal thickness was 198.5 micro (148 to
      283). The mean (SD) photoreceptor layer thickness was 16.5 (8) micro in the 500
      micro area and 17.5 (8) micro in the 1000 micro area. Mean (SD) of relative
      reflectivity of the photoreceptor layer was 0.60 (0.10) in both 500 micro and
      1000 micro area. Postoperative VA did not correlate with foveal thickness or
      foveal configuration. Central (500 micro and 1000 micro) photoreceptor thickness
      was significantly correlated with final VA (r = .38, P = .026, each). Relative
      reflectivity of photoreceptors to retinal pigment epithelium in the 500 micro
      area was correlated with postoperative VA at a borderline significance (r = .32,
      P = .07). Relative reflectivity of photoreceptors to retinal pigment epithelium
      in the 1000 micro area was not significantly correlated with postoperative VA (r
      = .27, P = .12). CONCLUSION: Specific retinal features can be assessed from OCT
      images. Morphology and thickness of the foveal photoreceptor layer correlate well
      with macular function after successful MHS. Outer retinal features appear to be
      more important to determine postoperative visual function. Inner retinal features
      may be more relevant for the ophthalmoscopic appearance of anatomic closure.

PMID- 15733990
TI  - Posterior subtenon triamcinolone acetonide for refractory diabetic macular edema.
AB  - PURPOSE: To evaluate posterior subtenon injection of triamcinolone acetonide for
      refractory diabetic macular edema (DME). DESIGN: Retrospective, interventional,
      case series. METHODS:  SETTING: Clinical practice. PATIENT POPULATION: Patients
      with persistent clinically significant DME involving the center of the fovea 3 or
      more months after one or more treatments of focal macular photocoagulation were
      included. Exclusion criteria were a history of corticosteroid-responsive
      intraocular pressure (IOP) rise, intraocular surgery within 3 months, and any
      laser treatment within 1 month. PROCEDURE: All patients received an ophthalmic
      history and examination including best-corrected Snellen visual acuity, IOP
      measurement, anterior segment examination including evaluation of lens status
      with LOCS II criteria, dilated fundus examination, and a posterior subtenon
      injection of 40 mg triamcinolone acetonide at baseline. Patients were reevaluated
      at 1, 3, 6, and 12 months after injection. RESULTS: Seventy-three injections were
      performed in 63 eyes of 50 patients. The mean baseline visual acuity was 20/80.
      Mean visual acuity significantly improved to 20/50 at 1 month, then stabilized to
      20/65 at 3 months, 20/68 at 6 months, and 20/63 at 12 months. Complications were
      rare, with a transient significant rise in intraocular pressure at the 3-month
      evaluation and ptosis in two patients. CONCLUSIONS: Visual acuities remained
      stable or improved over a 12-month period after posterior subtenon triamcinolone
      injections for refractory DME. There was a statistically significant improvement
      in visual acuity at 1 month.

PMID- 15733991
TI  - Objective analysis of retinal damage in HIV-positive patients in the HAART era
      using OCT.
AB  - PURPOSE: To assess retinal nerve fiber layer (RNFL) thickness in patients with
      human immunodeficiency virus (HIV) disease without cytomegalovirus retinitis
      (CMV). DESIGN: A case-control study. METHODS: The study included 113 eyes of 65
      patients in one center. Thickness of RNFL along a 3.4-mm-diameter circle centered
      on the optic nerve head was evaluated using third-generation optical coherence
      tomography. Patients in group A (39 eyes of 22 patients) were human
      immunodeficiency virus-negative control subjects. Group B (36 eyes of 18
      patients) was composed of HIV patients with no history of CMV retinitis and CD4
      counts consistently above 100. Group C (38 eyes of 25 patients) comprised HIV
      patients with no history of CMV retinitis but a history of CD4 count less than
      100 at some point lasting for at least 6 months. RESULTS: The average RNFL
      thicknesses in groups A, B, and C were 103.33 +/- 8.50 microm, 103.30 +/- 9.28
      microm, and 90.10 +/- 12.50 microm, respectively. Group C had significantly
      thinner overall RNFL than either of the groups A and B (Tukey-Kramer). This
      difference was most prominent in temporal, superior, and inferior retinal areas.
      No difference was in nasal retinal area, nor between groups A and B in any of the
      areas. CONCLUSIONS: Significant RNFL thinning occurs in HIV patients without CMV
      retinitis and with low CD4 counts compared with the same subgroup of patients
      with CD4 count increased to above 100 and HIV-negative control subjects. Third
      generation OCT may be useful in diagnosis of early subclinical HIV-associated
      visual functional loss.

PMID- 15733992
TI  - Vitrectomy surgery increases oxygen exposure to the lens: a possible mechanism
      for nuclear cataract formation.
AB  - PURPOSE: To report vitreous oxygen tension before, immediately after, and at
      longer times after vitrectomy. DESIGN: A prospective, interventional consecutive
      case series. METHODS: Oxygen was measured using an optical oxygen sensor in
      patients undergoing vitrectomy. Intraoperatively, oxygen measurements were taken
      before and after vitrectomy in two intraocular locations: adjacent to the lens
      and in the mid-vitreous. RESULTS: Sixty-nine eyes underwent oxygen tension
      measurements at the time of vitrectomy. In baseline eyes, oxygen tension in the
      vitreous was low, measuring 8.7 +/- 0.6 mm Hg adjacent to the lens and 7.1 +/-
      0.5 mm Hg in the mid-vitreous. The difference between the two locations was
      statistically significant (P < .003), indicating that vitreous gel maintains an
      intraocular oxygen gradient. Immediately after vitrectomy, oxygen tension in the
      fluid-filled eye was higher, measuring 69.6 +/-4.8 mm Hg adjacent to the lens and
      75.6 +/- 4.1 mm Hg in the mid-vitreous. There was no statistically significant
      oxygen gradient between the two locations. The difference in oxygen tension pre-
      and postvitrectomy is highly statistically significant (P < .0001 lens, P < .0001
      mid-vitreous). In eyes with a history of vitrectomy and previous removal of the
      vitreous gel, the intraocular oxygen tension was significantly higher than in
      eyes with a formed vitreous gel undergoing a first vitrectomy (P < .02 lens, P <
      .003 mid-vitreous). CONCLUSION: Vitrectomy surgery significantly increases
      intraocular oxygen tension during and for prolonged periods after surgery. This
      exposes the crystalline lens to abnormally high oxygen and may lead to nuclear
      cataract formation.

PMID- 15733993
TI  - Corneal endothelium and postoperative outcomes 15 years after penetrating
      keratoplasty.
AB  - PURPOSE: To determine changes in the central endothelium and thickness of grafted
      corneas and the cumulative probability of developing glaucoma, of graft
      rejection, and of graft failure 15 years after penetrating keratoplasty. DESIGN:
      Longitudinal cohort study of 500 consecutive penetrating keratoplasties by one
      surgeon. METHODS: Regrafted eyes, fellow eyes of bilateral cases, and patients
      not granting research authorization were excluded, leaving 388 grafts for
      analysis. At intervals after surgery, we photographed the endothelium and
      measured corneal thickness using specular microscopy. The presence of glaucoma,
      graft rejection, and graft failure were recorded. RESULTS: The 67 patients
      examined at 15 years represented 30% of the available clear grafts. Endothelial
      cell loss from preoperative donor levels was 71 +/- 12% (mean +/- standard
      deviation, n = 67), endothelial cell density was 872 +/- 348 cells/mm(2), and
      corneal thickness was 0.59 +/- 0.06 mm. Endothelial cell density was unchanged
      between 10 and 15 years, whereas corneal thickness increased (P = .001, n = 55).
      The mean annual rate of endothelial cell loss from 10 to 15 years after surgery
      was 0.2 +/- 5.7% (n = 54). The cumulative probability of developing glaucoma,
      graft rejection, or graft failure was 20%, 23%, and 28%, respectively, and 6 of
      the 8 graft failures after 10 years resulted from late endothelial failure.
      CONCLUSIONS: From 10 to 15 years after penetrating keratoplasty, the annual rate
      of endothelial cell loss was similar to that of normal corneas, corneal thickness
      increased, and late endothelial failure was the major cause of graft failure.

PMID- 15733994
TI  - Correlation between office and peak nocturnal intraocular pressures in healthy
      subjects and glaucoma patients.
AB  - PURPOSE: To evaluate the correlations between office-hour intraocular pressures
      (IOP) and peak nocturnal IOP in healthy and glaucomatous eyes. DESIGN:
      Retrospective review of laboratory records. METHODS: We reviewed 24-hour data of
      IOP collected from 33 younger healthy subjects (aged 18 to 25 years), 35 older
      healthy subjects (aged 40 to 74 years), and 35 untreated older glaucoma patients
      (aged 40 to 79 years) housed in a sleep laboratory. Measurements of IOP were
      taken every 2 hours using a pneumatonometer in the sitting and supine positions
      during the diurnal/wake period (7 AM to 11 PM) and in the supine position during
      the nocturnal/sleep period. Correlations between average sitting or supine IOP in
      the right eye between 9:30 AM and 3:30 PM (office hours) and peak right eye IOP
      during the nocturnal hours were analyzed. RESULTS: The average values of supine
      IOP during office hours were found to have the strongest correlation with peak
      nocturnal IOP in older glaucoma subjects (r = .713, P < .001), whereas the
      correlation was less in older healthy subjects (r = .523, P < .01) and was absent
      in younger healthy subjects (r = .224, P = .21). The correlation between average
      sitting IOP values during office hours and peak nocturnal IOP was also strong in
      older glaucoma subjects (r = .601, P < .001) and moderate in older healthy
      subjects (r = .412, P < .05), but absent in younger healthy subjects (r = -.077,
      P = .672). CONCLUSION: Using a modification of the diurnal IOP curve, the
      magnitude of peak nocturnal IOP in untreated glaucoma patients can be estimated
      during routine office visits. Supine IOP measurements estimate peak nocturnal IOP
      better than sitting measurements. This estimation may provide the clinician with
      valuable information regarding the nocturnal IOP peak in glaucoma patients.

PMID- 15733995
TI  - A technique to harvest Descemet's membrane with viable endothelial cells for
      selective transplantation.
AB  - PURPOSE: To describe a surgical technique using an artificial anterior chamber to
      facilitate harvest of Descemet's membrane (DM) and endothelium for corneal
      endothelial cell transplantation. DESIGN: Laboratory investigation. METHODS:
      Corneoscleral buttons of seven human donor eyes were mounted endothelial side up
      on an artificial anterior chamber. Keeping the endothelial side with its usual
      concavity, a manual trephination was made on the posterior surface with a 9.0-mm
      trephine, inside the Schwalbe line and just past the DM in depth. The chamber was
      filled with air, causing the endothelial side of the donor cornea to assume a
      convex configuration. The DM along with its endothelium was separated from the
      posterior stroma using a blunt cyclodialysis spatula. Drops of trypan blue 0.3%
      and alizarin red S 0.2% (n = 6) were applied. The stained DMs were examined under
      a light microscope and photographed to calculate the percentage of endothelial
      cell damage. Histology was done on the unstained cornea. RESULTS: The DM carrying
      endothelium was successfully removed from the posterior stroma in all seven eyes.
      Although the DM appears to be very friable, all samples were removed in toto
      without rupture. Vital staining showed a mean endothelial cell loss of 8.46%
      (standard deviation (SD) 6.9). Direct light microscopy demonstrated the
      preservation of endothelial cell morphology. CONCLUSIONS: This technique appears
      to be a safe and straightforward method to harvest DM for endothelial cell
      transplantation. Further studies are underway to determine the optimal method of
      insertion of the obtained healthy DM with endothelial cells through small corneal
      incisions.

PMID- 15733996
TI  - Mitomycin for pigmented conjunctival lesions.

PMID- 15733997
TI  - Primary placement of hydroxyapatite-coated sleeves in bioceramic orbital
      implants.

PMID- 15733998
TI  - Making sense out of wavefront sensing.

PMID- 15733999
TI  - In vivo demonstration of the anatomic differences between classic and occult
      choroidal neovascularization using optical coherence tomography.
AB  - PURPOSE: To determine architectural differences between classic and occult
      choroidal neovascularization (CNV) in vivo. DESIGN: Prospective observational
      case series. METHODS: Twenty-two patients with acute CNV underwent fluorescein
      angiography and optical coherence tomography (OCT), which were analyzed by
      separate blinded observers. RESULTS: In 87.5% of angiographically labeled
      "classic" CNV a discreet subretinal lesion corresponding to the neovascular
      complex could be seen above and separate to the retinal pigment epithelium on
      OCT. This was found in only 13.3% of "occult" CNV. CONCLUSION: With the latest
      commercially available OCT equipment it is now possible to confirm in vivo the
      previously proposed anatomic differences between fluorescein angiographically
      labeled classic and occult CNV. Classic CNV appear to grow predominantly in the
      subretinal space, whereas the majority of occult lesions do not. Optical
      coherence tomography features of CNV may correlate with response to photodynamic
      therapy or angiostatic treatments, as well as predicting the success of surgical
      removal.

PMID- 15734000
TI  - Optic disk size correlated with refractive error.
AB  - PURPOSE: To evaluate for which range of refractive error the optic disk size
      depends on, or is independent of, the refractive error. DESIGN: Clinical
      observational study. METHODS: The study included 1999 eyes of 1011 subjects with
      a mean refractive error of -0.97 +/- 2.72 diopters (range, -24.25 to +9.4
      diopters). Optic disk photographs were morphometrically evaluated. RESULTS: The
      relation between optic disk area and refractive error showed a curvilinear shape,
      with a steep increase toward high myopia starting at -8 diopters, and a decrease
      toward high hyperopia starting at +4 diopters. CONCLUSION: The optic disk size
      depends on the refractive error with an increase in highly myopic eyes beyond -8
      diopters and a decrease in highly hyperopic eyes beyond +4 diopters. Confirming
      histomorphometric studies, the limits of -8 diopters and +4 diopters may be
      discussed to refine the definitions of high hyperopia and high myopia.

PMID- 15734001
TI  - Serous retinal detachment in an elderly patient with Philadelphia-chromosome
      positive acute lymphoblastic leukemia.
AB  - PURPOSE: To describe an elderly woman who presented with a serous retinal
      detachment (SRD) as the first sign of Philadelphia-chromosome-positive acute
      lymphoblastic leukemia (Ph(+) ALL). DESIGN: Observational case report. METHODS: A
      complete ophthalmic and systemic evaluation was performed on a 62-year-old woman
      because of decreased vision of 20/60 OD and 20/25 OS. RESULTS: Fundus examination
      revealed a SRD involving the fovea, OU. Fluorescein angiography disclosed
      multifocal spots of hyperfluorescence in the early phase, and diffuse subretinal
      accumulation of fluorescein in the late phase. She was diagnosed with Ph(+) ALL
      because of systemic findings. She underwent systemic chemotherapy and went into
      complete remission. Visual acuity improved to 20/20 in both eyes with resolution
      of the bilateral SRD. CONCLUSIONS: Our observations indicate that a sudden
      appearance of SRD, even in an elderly patient, warrants a thorough systemic
      screening for underlying leukemia. This is especially important, because prompt
      systemic chemotherapy can improve the visual acuity and the prognosis.

PMID- 15734002
TI  - The genotype of Toxoplasma gondii strains causing ocular toxoplasmosis in humans
      in Brazil.
AB  - PURPOSE: To determine Toxoplasma gondii genotype in scars of retinochoroiditis in
      humans. DESIGN: Immunopathology analysis. METHODS: DNA was isolated from
      retinochoroidal specimens taken from the borders of the scars from eye bank eyes
      as well as enucleated eyes from uveitis patients with retinochoroidal toxoplasmic
      scars. The SAG2 region was amplified by polymerase chain reaction and analyzed by
      restriction fragment length polymorphism. RESULTS: Of the 92 eyes studied, 9 had
      toxoplasmic scars. All of them, as well as the 2 enucleated eyes, disclosed the
      presence of type I parasites by the gel electrophoresis analysis of the
      restriction fragment length polymorphism from SAG2. CONCLUSION: These results
      suggest that type I strain seems to be responsible for the ocular infections in
      the population studied.

PMID- 15734003
TI  - Optical coherence tomography in Best's disease: an observational case report.
AB  - PURPOSE: To report the optical coherence tomographic (OCT) findings in a case of
      Best's disease. DESIGN: Observational case report. METHODS: Optical coherence
      tomography was carried out to understand the pathogenesis of Best's disease in a
      13-year-old girl. RESULTS: Optical coherence tomography demonstrated that the
      lipofuscin accumulated in a cystic space underneath the retinal pigment
      epithelium in the "pseudohypopyon stage" of Best's disease. It also demonstrated
      the disruption of the photoreceptors in the "scrambled egg" stage. CONCLUSIONS:
      These new OCT findings could explain the retention of good visual acuity in the
      "pseudohypopyon stage" and the loss of visual acuity in the "scrambled egg" stage
      of Best's disease.

PMID- 15734005
TI  - Unilateral keratoconus in a child with chronic and persistent eye rubbing.
AB  - PURPOSE: To report a case of unilateral keratoconus in a 7- year-old female,
      secondary to chronic persistent eye-rubbing in the absence of any systemic
      condition. DESIGN: Observational case report. METHODS: In the case of this child,
      no organic cause was found to explain the onset of keratoconus other than
      persistent eye-rubbing in the affected eye. RESULTS: Nocturnal eye padding was
      instigated and the condition stabilized. She was reviewed over a 2-year period of
      follow-up. CONCLUSIONS: Eye-rubbing has been implicated in the pathogenesis of
      keratoconus. Eye-rubbing is also often a feature of a number of conditions linked
      to keratoconus such as Down syndrome, atopic keratoconjunctivitis, mental
      retardation, and Lebers' congenital amaurosis. There are a number of reports
      linking eye-rubbing and keratoconus in children, typically in relation to these
      conditions. However, in this case the keratoconus was secondary to chronic and
      persistent eye-rubbing in a healthy child.

PMID- 15734004
TI  - Near-infrared spectroscopy of the visual cortex in unilateral optic neuritis.
AB  - PURPOSE: To examine the occipital-lobe activation of patients with optic neuritis
      using near-infrared spectroscopy. DESIGN: Experimental study. METHODS: NIRS was
      performed on five patients with acute unilateral optic neuritis during monocular
      visual stimulation. As controls, six normal subjects were also tested in the same
      manner. RESULTS: In the patients with optic neuritis, the changes in the
      hemoglobin concentrations (oxyhemoglobin, deoxyhemoglobin, and total hemoglobin)
      in the occipital lobe were found to be markedly reduced when the clinically
      affected eyes were stimulated compared with the fellow eyes. The response induced
      by the stimulation of the affected eye was decreased, even when the patient's
      visual acuity improved to 20/20 in the recovery phase. There was no difference in
      the concentration changes between the two eyes in the control subjects.
      CONCLUSIONS: NIRS may be useful in detecting visual dysfunction objectively and
      noninvasively in patients with visual disturbance, especially when used at the
      bedside.

PMID- 15734006
TI  - Macular hole secondary to epiretinal membrane in a juvenile patient.
AB  - PURPOSE: To report a macular hole secondary to an idiopathic epiretinal membrane
      in a 14-year-old girl. DESIGN: Interventional case report. METHODS: A 3-year-old
      girl who failed a public visual-screening test was examined. Since then, she had
      been followed-up for her epiretinal membrane, which began to peel spontaneously
      in the left eye for 11 years until a macular hole was observed. She was treated
      by vitrectomy and membranectomy, and the membrane was histologically examined.
      RESULT: The macular hole was successfully closed, and her visual acuity improved.
      The membrane appeared to have a homogenous structure and contained no cells.
      CONCLUSIONS: The juvenile idiopathic epiretinal membrane sometimes peels
      spontaneously. However, long-term follow-up is needed because vitreous traction
      of the membrane by intraocular aging change may result in a macular hole.

PMID- 15734007
TI  - Fundus abnormalities in a patient with type I Gaucher's disease with 12-year
      follow-up.
AB  - PURPOSE: To report a case of type I Gaucher's disease with rare presentation of
      fundus abnormalities in long-term observation. DESIGN: Observational case report.
      METHODS: This 53-year-old Taiwanese woman suffered from type I Gaucher's disease
      for 12 years, with initial presentation of hepatoslpenomegaly in 1992. RESULTS:
      At that time, poor vision with unusual macular change and peripheral retinal
      vessel leakage was also noted. She received a complete ophthalmic examination at
      the initial visit and again 12 years later in 2003. She was treated with
      imiglucerase injection during the last 4 years. However, her visual acuity was
      10/200 in both eyes. The macular and peripheral retinal degenerative change
      progressed after 12 years. CONCLUSIONS: Fundus changes associated with Gaucher's
      disease are uncommon. We should not neglect the possibility of retinal
      involvement and progression in these patients.

PMID- 15734008
TI  - New ophthalmic manifestations of branchio-oculo-facial syndrome.
AB  - PURPOSE: To report new ocular manifestations of branchio-oculo-facial (BOF)
      syndrome. DESIGN: Case report. METHODS: A 10-year-old girl with known BOF
      syndrome was referred because of a fundus lesion in her left eye. RESULTS: She
      had undergone excision of a left orbital dermoid cyst at age 18 months and a
      branchial cleft fistula from the right side of neck at age 4 years. Examination
      disclosed openings of sinus tracts on each side of the nose connecting the
      lacrimal sac to skin. In the right eye, an iris pigment epithelial cyst was
      confirmed with ultrasound biomicroscopy. In the left eye, there was a combined
      hamartoma of the retina and retina pigment epithelium. CONCLUSION: BOF syndrome
      can display mild to severe craniofacial, auricular, oral, and ophthalmic
      anomalies. In this case, the ophthalmic manifestations included lacrimal sac
      fistula, orbital dermoid cyst, iris pigment epithelial cyst, and combined
      hamartoma of the retina and retinal pigment epithelium.

PMID- 15734009
TI  - Sclerochoroidal calcification in a patient with classic Bartter's syndrome.
AB  - PURPOSE: To report sclerochoroidal calcification in a patient with classic
      Bartter's syndrome. DESIGN: Observational case report. METHODS: A 42-year-old
      woman with a 26-year history of classic Bartter's syndrome was found to have
      bilateral fundus tumors. The patient presented initially with quivering lips and
      hand stiffness at age 6 years but was not diagnosed until age 16 years. Treatment
      included magnesium and potassium supplementation and Amiloride therapy. RESULTS:
      On ocular examination, there were multifocal, yellow-white, geographic, solid
      choroidal lesions along the superior and inferior retinal vascular arcades in
      both eyes. Ultrasonography showed echogenic, placoid calcified lesions at the
      level of the sclera and choroid, consistent with bilateral sclerochoroidal
      calcification. CONCLUSIONS: Sclerochoroidal calcification can be associated with
      classic Bartter's syndrome.

PMID- 15734010
TI  - Oprelvekin-associated bilateral optic disk edema.
AB  - PURPOSE: To report a case of bilateral optic disk edema in a patient taking
      oprelvekin for radioimmunotherapy-induced thrombocytopenia. DESIGN: Observational
      case report. METHODS: A 38-year-old man with a history of relapsed non-Hodgkins
      follicular lymphoma complained of bilateral loss of vision following oprelvekin
      therapy for thrombocytopenia. RESULTS: Funduscopic examination demonstrated
      bilateral optic disk edema with exudates inferotemporal to the right nerve. The
      results of magnetic resonance imaging of the brain and orbits and lumbar puncture
      were normal. The disk edema resolved with discontinuation of oprelvekin therapy.
      CONCLUSIONS: Oprelvekin therapy may be associated with bilateral optic disk
      edema. This has been shown to be reversible in a primate model.

PMID- 15734011
TI  - Acute corneal hydrops treated by intracameral injection of perfluoropropane
      (C3F8) gas.
AB  - PURPOSE: To report a case of acute hydrops with intrastromal cleft in a patient
      of keratoconus with associated Marfan's syndrome, treated with intracameral
      injection of perfluoropropane (C(3)F(8)) gas. DESIGN: Interventional case report.
      METHODS: A nonexpansile concentration of perfluoropropane gas (0.2 ml) was
      injected intracamerally in the operating room under aseptic precautions. RESULTS:
      There was complete and rapid resolution of corneal edema. CONCLUSION:
      Intracameral perfluoropropane gas in nonexpansile concentration may be a useful
      modality for treatment of corneal edema in acute corneal hydrops.

PMID- 15734012
TI  - Bilateral endogenous Scedosporium prolificans endophthalmitis after lung
      transplantation.
AB  - PURPOSE: To report a case of bilateral endogenous fungal endophthalmitis
      resulting from disseminated Scedosporium prolificans. DESIGN: Observational case
      report. METHODS: A 56-year-old woman with cystic fibrosis status post dual lung
      transplantation on chronic immunosuppressive therapy presented with acute graft
      rejection. Cultures of bronchial brushings revealed S. prolificans. Three weeks
      after admission, the patient noted increased blurriness and a central scotoma in
      her right eye. Dilated fundus examination revealed profound vitritis in the right
      eye with hemorrhagic retinitis involving the macula. A peripheral, yellow
      choroidal infiltrate with overlying retinitis and localized vitritis was present
      in the left eye. RESULTS: Intravitreal antibiotics were initiated, and vitreous
      cultures revealed S. prolificans. The patient ultimately succumbed to her
      disseminated disease. Pathologic examination of the eyes confirmed bilateral
      endogenous fungal endophthalmitis. CONCLUSION: S. prolificans is an opportunistic
      infection resistant to standard antifungal therapy that can result in endogenous
      endophthalmitis in immunocompromised individuals.

PMID- 15734013
TI  - Medication use and retinal vessel diameters.
AB  - PURPOSE: To study the influence of different medications on retinal vessel
      diameters. DESIGN: Cross-sectional study. METHODS: Retinal photographs in the
      Beaver Dam Eye Study (n = 4926, aged 43 to 84 years) were digitized, and the
      diameters of retinal vessels were measured. Participants' current medications
      were recorded at the examination. RESULTS: There were few significant
      associations between medication use and retinal vessel diameters. After adjusting
      for age, blood pressure, and other factors, participants who were using topical
      beta-blocker eyedrops had narrower retinal arteriolar (P = .05) and venular (P =
      .006) diameters than nonusers. Systemic beta-blocker was not associated with
      retinal vessel diameter size. CONCLUSION: We found few associations between
      current medication use and retinal vessel diameter. Retinal vessels were narrowed
      in those taking antiglaucoma medications, most strikingly in those prescribed
      topical beta-blockers, although such a relationship could not be established
      among those using systemic beta-blockers.

PMID- 15734014
TI  - Laser in situ keratomileusis in a patient with presumed central cloudy corneal
      dystrophy of Francois.
AB  - PURPOSE: To report a case of laser in situ keratomileusis (LASIK) surgery
      performed in a patient with likely central cloudy corneal dystrophy of Francois
      (CCDF). DESIGN: Observational case report. METHODS: A 48-year-old woman with
      likely CCDF had myopic LASIK to establish monovision. Outcome measures included
      visual acuity, manifest refraction, and slit-lamp examination. RESULTS: At 5-year
      follow-up, the patient had uncorrected visual acuity of 20/100, J1, in the right
      eye (OD) and 20/20 in the left eye (OS), consistent with monovision correction.
      Manifest refraction was -1.50 OD and -0.25 OS postoperatively; after retreatment
      at 1 year for regression, the left eye remained stable over the subsequent 4-year
      period. Slit-lamp examination revealed no progression of corneal opacities in
      either eye. CONCLUSIONS: LASIK may be safe and effective in patients with CCDF.
      Further observations of a greater number of patients are required to confirm
      these findings.

PMID- 15734015
TI  - New micro vertical scissors for the surgical ablation of retinal angiomatous
      proliferation.
AB  - PURPOSE: To develop new micro vertical scissors for the ablation of retinal
      angiomatous proliferation (RAP) to minimize possible retinal damage. DESIGN:
      Interventional case report. METHODS: New micro vertical scissors were developed
      and used for the ablation of RAP vessels. RESULTS: The length of the inner side
      of the tip is 180 microm, which is approximately one seventh that of regular
      vertical scissors. The scissors handled easily and the RAP vessels were ablated
      with less retinal damage compared with that associated with use of standard
      vertical scissors. Postoperatively, intraretinal hemorrhage was reduced and
      hyperfluorescence seen on indocyanine green angiography resolved. CONCLUSIONS:
      The new micro vertical scissors developed for the ablation of RAP vessels can be
      used safely and effectively during this surgical procedure.

PMID- 15734016
TI  - Primary embryonal carcinoma of the orbit in a 10-month-old female: a seven-year
      follow-up.
AB  - PURPOSE: Extra-gonadal germ cell tumors (GCTs) are rare and can be highly
      aggressive. If correctly identified and treated with multimodality chemotherapy,
      their prognosis can be significantly improved. We examined a 10 month-old female
      with primary embryonal carcinoma of the orbit. DESIGN: Case report and literature
      review. METHODS: Case study with 7-year follow-up and literature review of
      intracranial and intraorbital GCT cases. RESULTS: The patient presented with
      progressive proptosis and ophthalmoplegia. CT scan revealed an orbital apex mass
      and biopsy demonstrated a nongerminomatous GCT--an embryonal carcinoma. The
      patient is tumor-free 7 years after multimodality chemotherapy. She has mild
      amblyopia and a right micro esotropia. CONCLUSIONS: Nongonadal GCTs of the orbit
      can occur and should be considered in the differential diagnosis of a young child
      with proptosis and ophthalmoplegia. Five-year survival rates improve
      significantly with accurate identification and treatment.

PMID- 15734017
TI  - Argon laser iridoplasty in the treatment of plateau-like iris configuration as
      result of numerous ciliary body cysts.
AB  - PURPOSE: To report the use of argon laser peripheral iridoplasty in the treatment
      of plateau-like iris configuration as a result of iris and ciliary body cysts.
      DESIGN: Case report. METHODS: A 43-year-old male with plateau iris syndrome was
      demonstrated by high frequency ultrasound biomicroscopy (UBM), to have numerous
      iris and ciliary body cysts. Bilateral argon laser peripheral iridoplasty was
      performed. RESULTS: Argon laser iridoplasty opened the drainage angle in both
      eyes. CONCLUSION: Argon laser iridoplasty is an effective and safe treatment for
      plateau iris syndrome and may also prove valuable in the treatment of plateau
      like iris configuration resulting from iridociliary cysts.

PMID- 15734018
TI  - Idiopathic macular hole with extensive subretinal fluid: clinical and optical
      coherence tomography features before and after surgery.
AB  - PURPOSE: To report clinical and optical coherence tomography (OCT) features in
      patients with idiopathic macular hole and extensive subretinal fluid (extending
      at least 1 disk diameter from the center of the hole). DESIGN: Retrospective,
      consecutive, noncomparative case series. METHODS: The case records of two
      patients with idiopathic macular holes with extensive subretinal fluid were
      reviewed. RESULTS: Both patients presented with reduced visual acuity (20/200 and
      20/400). OCT demonstrated attachment of the posterior hyaloid to the inner
      retina, a full-thickness macular hole, cystoid macular edema (CME), and extensive
      subretinal fluid. After surgery, both patients achieved macular hole closure and
      improvement in visual acuity (20/60 and 20/30). Postoperatively, OCT showed a
      normal foveal contour, complete hole closure, and resolution of the CME and
      subretinal fluid. CONCLUSIONS: In patients with macular hole and extensive
      subretinal fluid, improved visual acuity and hole closure can be achieved.
      Preoperative OCT in these patients demonstrates vitreoretinal interface
      abnormalities, CME, and extensive subretinal fluid. These changes resolve
      postoperatively.

PMID- 15734019
TI  - Histopathologic study of X-linked cone-rod dystrophy (CORDX1) caused by a
      mutation in the RPGR exon ORF15.
AB  - PURPOSE: To evaluate the donor retina of a patient with X-linked cone-rod
      dystrophy caused by an RPGR exon ORF15 mutation. DESIGN: Histopathologic study of
      the retina. METHODS: The eye of a 69-year-old man was fixed at 1.6 hours
      postmortem and processed for histopathology and immunocytochemistry. RESULTS:
      Grossly, the macula was atrophic with a bull's-eye appearance. The remaining
      retina showed postmortem edema but no intraretinal pigment. Microscopically, the
      macular retinal pigment epithelium was absent focally and had pigmentary changes
      elsewhere. Cones and rods were absent from the perifovea and reduced with
      shortened outer segments elsewhere in the macula. In the remainder of the retina,
      cones but not rods were reduced and all photoreceptor outer segments were
      shortened. CONCLUSIONS: The abnormalities in both cone and rod photoreceptors
      confirm the importance of RPGR in both cell types but leaves unresolved how
      various exon ORF15 mutations lead to different clinical phenotypes.

PMID- 15734021
TI  - Indocyanine green-assisted internal limiting membrane removal in epiretinal
      membrane surgery.

PMID- 15734023
TI  - Optical coherence tomography under general anesthesia in a child with nystagmus.

PMID- 15734025
TI  - Corneal thickness measurement by confocal microscopy, ultrasound, and scanning
      slit methods.

PMID- 15734026
TI  - Inflow of ocular surface fluid through clear corneal cataract incisions: a
      laboratory model.

PMID- 15734027
TI  - Current and future role of photodynamic therapy in chronic central serous
      chorioretinopathy.

PMID- 15734029
TI  - Clinical features associated with lesions other than pituitary adenoma in
      patients with an optic chiasmal syndrome: a new perspective.

PMID- 15734032
TI  - A prospective multicenter clinical trial to evaluate the safety and effectiveness
      of the implantable miniature telescope.

PMID- 15734035
TI  - Retinal striae after surgical and spontaneous ILM-peeling.

PMID- 15734036
TI  - Plant-derived vaccines and antibodies: potential and limitations.

PMID- 15734037
TI  - Vaccines and sera through plant biotechnology.

PMID- 15734038
TI  - Opportunities for recombinant antigen and antibody expression in transgenic
      plants--technology assessment.
AB  - Plants are now gaining widespread acceptance as a general platform for the large
      scale production of recombinant proteins. The principle has been demonstrated by
      the success of a diverse repertoire of proteins, with therapeutic molecules
      showing the most potential for added value. Over the past 10 years, several
      efficient plant-based expression systems have emerged. However, a number of
      issues remain to be addressed before plant bioreactors can be accepted and
      adopted widely in preference to the established microbial and mammalian
      platforms. Overcoming bottlenecks imposed by low yields, poor and inconsistent
      product quality and difficulties with downstream processing are the most
      important goals for researchers working in this field. The achievement of these
      goals is conditional on the development of extraction and processing steps that
      comply with GMP standards, including extensive quality assurance and control
      procedures. Such rigorous and validated standards should be combined with
      measures applied earlier in production to ensure product sustainability and
      quality, such as the use of master seed banking procedures. Moreover, there are
      several further challenges concerning topics of environmental impact, biosafety
      and risk assessment, which reflect the release of transgenic plants, as well the
      safety of the plant-derived products themselves. We are facing a growing demand
      for protein diagnostics and therapeutics, but lack the capacity to meet those
      demands using established facilities. A shift to plant bioreactors may,
      therefore, become necessary within the next few years, making it more imperative
      that the technical and regulatory limitations are addressed and solved. The
      production of pharmaceutical proteins in plants will only realize its huge
      potential if the products are provided at consistent high quality levels,
      allowing the delivery of clinical grade proteins that will gain regulatory
      approval and which can be used routinely in clinical trials.

PMID- 15734039
TI  - Protein modifications in the plant secretory pathway: current status and
      practical implications in molecular pharming.
AB  - Plants have become, over the last ten years, a suitable alternative to microbial
      and animal cell factories for the production of clinically-useful, therapeutic
      proteins. Besides the well known advantage of low-cost and large-scale production
      of safe and biologically active mammalian proteins, plants also are able to
      perform most post-translational maturations required for biological activity and
      suitable pharmacokinetics of recombinant therapeutic proteins. In this short
      review we focus on glycosylation and proteolytic processing of plant-made
      pharmaceuticals during their transport through the plant cell's secretory
      pathway. We also address the practical implications of these important processes
      on the effectiveness of plant molecular pharming systems.

PMID- 15734040
TI  - Chloroplast-derived vaccine antigens and other therapeutic proteins.
AB  - The chloroplast genetic engineering offers a number of unique advantages
      including high level of transgene expression, multi-gene expression in single
      transformation event and transgene containment due to maternal inheritance. Hyper
      expression of vaccine antigens or therapeutic proteins in transgenic chloroplasts
      (leaves) or chromoplasts (fruits/roots) facilitates efficient oral delivery.
      Ability of chloroplasts to correctly fold human blood proteins with proper
      disulfide bridges (human serum albumin or interferons) or presence of chaperones
      in chloroplasts to facilitate assembly of complex multi-subunit proteins or their
      prokaryotic nature to express native bacterial genes (up to 46.1% total leaf
      protein) are attractive features for therapeutic protein production. Purification
      of therapeutic proteins has been achieved using novel purification strategies
      that do not require expensive column chromatography.

PMID- 15734041
TI  - Viral and host determinants of RNA virus vector replication and expression.
AB  - Positive-strand RNA viruses have proven to be valuable vectors for delivery and
      expression of antigens for direct vaccination of animals and vaccine production
      in plants. However, optimal use of these viruses as vectors for vaccine and other
      purposes is limited by incomplete understanding of their replication pathways and
      associated constraints on inserted foreign genes. Further insights into RNA virus
      vector design and optimization are emerging from recent advances on the function
      of viral RNA replication factors, the nature of the viral RNA replication complex
      as a membrane-bounded compartment sequestering replication components from
      competing processes and host defenses, and identification of surprisingly diverse
      host genes contributing to many virus replication steps.

PMID- 15734042
TI  - Cowpea mosaic virus-based systems for the production of antigens and antibodies
      in plants.
AB  - Cowpea mosaic virus (CPMV) is a bipartite RNA plant virus which has proved to be
      useful both for epitope presentation and as a polypeptide expression system. For
      epitope presentation, short antigenic sequences are expressed on the surface of
      the assembled virus. Chimaeric virus particles produced in this way can stimulate
      protective immunity in experimental animals. For polypeptide expression, we have
      created a vector in which foreign sequences can be inserted near the 3' end of
      RNA-2 and have successfully expressed a number of polypeptides in plant tissue.
      To extend the utility of the CPMV-based systems, we have recently developed a
      combined virus vector/transgenic expression system in which RNA-2 expressed from
      a transgene is replicated by RNA-1.

PMID- 15734043
TI  - Uptake and presentation of orally administered antigens.
AB  - The mucosae of the gastrointestinal tract are continuously exposed to a myriad of
      antigens and microorganisms that the immune system has to discriminate between
      dangerous and harmless. Entry of pathogenic microorganisms occurs mainly via M
      cells that are concentrated in the follicle-associated epithelium overlying the
      Peyer's Patches (PPs). M cells are very selective and do not allow entry of all
      microorganisms. We have recently described an additional mechanism by which
      dendritic cells (DCs) can monitor the contents of the intestinal lumen. DCs send
      dendrites outside the epithelium, like periscopes. It is not clear whether this
      mechanism is constitutively active or is induced in response to signals from
      epithelial cells that have been in contact with pathogens or high numbers of non
      pathogenic bacteria in the lumen. Therefore, deciphering the signals that are
      released by epithelial cells after the encounter with mucosal antigens is of
      paramount importance to understand the ability of the DCs to respond to the
      different antigens and to mount immune or tolerogenic responses.

PMID- 15734044
TI  - Dendritic cells and immune responses to orally administered antigens.
AB  - The intestinal immune system discriminates between invasive pathogens and
      antigens that are harmless, such as food proteins and commensal bacteria. The
      latter groups of antigens normally induce tolerance and the nature of the
      intestinal immune response depends on how antigen is presented to CD4+ T cells by
      dendritic cells (DC). Expanding the numbers of DC in vivo using the cytokine flt3
      ligand (flt3L) enhances the susceptibility of mice to the induction of oral
      tolerance. The relevant DC may be in Peyer's patches (PP), mesenteric lymph node
      (MLN) or the lamina propria (LP)of the villus mucosa. All these tissues contain a
      number of distinctive DC subsets, including some that can preferentially induce
      the differentiation of regulatory T cells. However, we find that the largest
      proportion of orally administered protein is taken up by DC in the lamina
      propria. Intestinal DC are not inherently tolerogenic. Under physiological
      conditions they are "quiescent", capable of presenting antigen and inducing
      tolerance, but being sufficiently responsive to inflammatory stimuli to allow T
      cell priming and protective immunity when necessary. Targeting local DC may be a
      useful means of inducing either tolerance or active immunity. We have achieved
      this using immune stimulating complexes (ISCOMS) containing Quil A, which are
      highly immunogenic by the oral route and appear to act by targeting DC
      preferentially. ISCOMS or saponins such as Quil A may prove useful adjuvants to
      incorporate in plant derived, mucosally active vaccines.

PMID- 15734045
TI  - Immune response versus mucosal tolerance to mucosally administered antigens.
AB  - The enhancement of protective mucosal responses to infectious agents sought by
      vaccinologists, and the desired suppression of immune responses to autoantigens,
      allergens and food antigens induced by mucosal exposure to relevant antigens, may
      seem paradoxical. However, such outcomes are not mutually exclusive because of a
      hierarchy in the quality of immune responses: mucosal immunity manifested by the
      appearance of secretory antibodies and systemic tolerance manifested by
      diminished cell-mediated responses may be induced concomitantly. We have
      demonstrated that the ingestion, or nasal application, of a neo-antigen-keyhole
      limpet hemocyanin (KLH)-primes human volunteers for subsequent humoral mucosal
      and systemic responses induced by systemic immunization but suppresses cell
      mediated responses (T cell proliferation and delayed-type hypersensitivity).
      Furthermore, extended ingestion of selected food antigens diminished, but did not
      totally suppress, cell-mediated immunity and levels of serum antibodies while
      salivary antibodies were easily detectable. Most importantly, the humoral and
      cellular immune responses induced by systemic immunization with KLH could not be
      suppressed by subsequent extended ingestion of large doses of the same antigen.
      Thus, ongoing systemic responses are refractory to the induction of mucosal
      tolerance in humans. This finding is of considerable importance for the
      development of and sequence of immunization with mucosally administered vaccines.

PMID- 15734046
TI  - Mucosal adjuvants.
AB  - Induction of immune responses following oral immunization is frequently dependent
      upon the co-administration of appropriate adjuvants that can initiate and support
      the transition from innate to adaptive immunity. The three bacterial products
      with the greatest potential to function as mucosal adjuvants are the ADP
      ribosylating enterotoxins (cholera toxin and the heat-labile enterotoxin of
      Escherichia coli), synthetic oligodeoxynucleotides containing unmethylated CpG
      dinucleotides (CpG ODN), and monophosphoryl lipid A (MPL). The mechanism of
      adjuvanticity of the ADP-ribosylating enterotoxins is the subject of considerable
      debate. Our own view is that adjuvanticity is an outcome and not an event. It is
      likely that these molecules exert their adjuvant function by interacting with a
      variety of cell types, including epithelial cells, dendritic cells, macrophages,
      and possibly B- and T-lymphocytes. The adjuvant activities of CpG and MPL are due
      to several different effects they have on innate and adaptive immune responses
      and both MPL and CpG act through MyD88-dependent and -independent pathways. This
      presentation will summarize the probable mechanisms of action of these diverse
      mucosal adjuvants and discuss potential synergy between these molecules for use
      in conjunction with plant-derived vaccines.

PMID- 15734047
TI  - Antibody processing and engineering in plants, and new strategies for vaccine
      production.
AB  - The use of transgenic plants for the production of recombinant proteins is not a
      universal solution for all proteins. The choice of this expression system depends
      very much on the type of protein and its applications. Many proteins will best be
      made by conventional microbial fermentation, similarly, we are already
      identifying proteins where plants represent the only practical option for one
      reason or another. It will be important to understand better the cellular
      mechanisms of protein folding, assembly and processing in plants, in order to
      maximise the potential of transgenic plants as a protein production system. One
      of the main advantages that plants offer is that they are higher eukaryotic
      organisms with an endomembrane system. Therefore, they fold and assemble
      recombinant proteins using protein chaperones that are homologous to those in
      mammalian cells, and they perform post-translational modifications. This allows,
      for example, the expression of monoclonal antibodies, first described in 1989, as
      well as a range of other types of immunoglobulin molecules and multimeric
      complexes.

PMID- 15734048
TI  - Preventing transmission: plant-derived microbicides and mucosal vaccines for
      reproductive health.
AB  - Exclusion of infectious agents from mucosal surfaces of the reproductive tract is
      a key objective of microbicides and mucosal vaccines. With mucosal antibodies as
      a common mechanism of exclusion, parallel development of passive and active
      immunization strategies is an opportunity to determine and achieve protective
      antibody concentrations in the female reproductive tract. Recognizing that access
      to sexual and reproductive health products will require low-cost and high
      capacity production technologies, the emerging tools of plant biotechnology for
      complex biopharmaceutical production are crucial. Unfortunately, few preclinical
      or clinical studies have been completed to date with plant-derived agents
      intended for reproductive health.

PMID- 15734049
TI  - Expression of single-chain antibodies in transgenic plants.
AB  - There is an ever-growing interest in plant molecular farming as a system for
      producing valuable recombinant pharmaceutical molecules, such as single-chain
      variable fragments, on an industrial/agricultural scale and it appears that it is
      going to become a reality. Human epidermal growth factor receptor-2 (HER2) is an
      oncogene involved in abnormal cell growth in breast cancer and is considered for
      the development of new cancer therapies. We describe here the cloning and
      expression of a scFv-alpha HER2 that has been produced in Escherichia coli and in
      plants using both stable and transient systems in tobacco and Nicotiana
      benthamiana. Single-chain antibodies (ScFvs) extracted and purified from E. coli
      and plant tissues were tested for functionality and specificity by flow cytometry
      analysis on several cell lines and showed positive results when used on breast
      cancer slides coming from human frozen tissues. As a result, scFv-alpha HER2
      represents a good opportunity for application and use in diagnosis and therapy.

PMID- 15734050
TI  - Expression of human antibodies in eukaryotic micro-algae.
AB  - Protein based therapeutics have enjoyed great success over the past decade.
      Unfortunately, with this clinical success comes a heavy price tag, owing to the
      inherently high costs of capitalization and production using mammalian cell
      fermentation. To address this problem, we have begun developing a system for the
      expression of recombinant proteins in the unicellular eukaryotic green algae,
      Chlamydomonas reinhardtii, leading to the production of human IgA single chain
      antibodies. The expression of human monoclonal antibodies in C. reinhardtii
      offers an attractive alternative to traditional mammalian based expression
      systems for several reasons, including an ability to rapidly obtain stable
      plastid and nuclear transformants, coupled with inherently low costs of
      capitalization and production.

PMID- 15734052
TI  - Development of transgenic alfalfa plants containing the foot and mouth disease
      virus structural polyprotein gene P1 and its utilization as an experimental
      immunogen.
AB  - The use of transgenic plants as vectors for the expression of viral and bacterial
      antigens has been increasingly tested as an alternative methodology for the
      production of experimental vaccines. Here, we report the production of transgenic
      alfalfa plants containing the genes encoding the polyprotein P1 and the protease
      3C of foot and mouth disease virus (FMDV). The immunogenicity of the expressed
      products was tested using a mouse experimental model. Parenterally immunized mice
      developed a strong antibody response and were completely protected when
      challenged with the virulent virus. This report demonstrates the possibility of
      using transgenic plants to express polyprotein P1 and the protease 3C of FMDV and
      their utilization as effective experimental immunogens.

PMID- 15734051
TI  - An integral approach towards a practical application for a plant-made monoclonal
      antibody in vaccine purification.
AB  - The use of transgenic plants for the production of pharmaceutical compounds has
      received increasing attention in the last few years. However, many technological
      and regulatory issues regarding the practical exploitation of this alternative
      system of production remain to be solved; a situation that explains the lack of
      commercial products derived from such a system. This paper reports the expression
      in transgenic plants and cells of a single-chain antibody variable-region
      fragment (scFv) and a mouse monoclonal antibody to the hepatitis B virus surface
      antigen (HBsAg). The large-scale purification of the scFv from plants and its use
      for immunopurification of HBsAg are also described, together with elements
      concerning regulatory issues and technologies for compliance with good
      manufacturing and agricultural practices.

PMID- 15734053
TI  - Immunoprotective properties of transgenic plants expressing E2 glycoprotein from
      CSFV and cysteine protease from Fasciola hepatica.
AB  - Immune responses were elicited in laboratory animals after oral vaccination by
      transgenic plants (lettuce and alfalfa) expressing the E2 glycoprotein of
      Classical Swine Fever Virus (CSFV) or cysteine protease from Fasciola hepatica.
      ELISA analyses demonstrated that the oral route is effective in inducing a
      specific antibody response against these antigens in mice.

PMID- 15734054
TI  - Plant-based immunocontraceptive control of wildlife--"potentials, limitations,
      and possums".
AB  - Possums (Trichosurus vulpecula), originally introduced from Australia, are spread
      over 90% of New Zealand and cause major economic and environmental damage.
      Immunocontraception has been suggested as a humane means to control them.
      Marsupial-specific reproductive antigens expressed at high levels in edible
      transgenic plant tissue might provide a safe, effective, and cheap oral delivery
      bait for immunocontraceptive control. As proof of concept, female possums
      vaccinated with immunocontraceptive antigens showed reduced fertility, and
      possums fed with potato-expressed heat labile toxin-B (LT-B) had mucosal and
      systemic immune responses to the antigen. This demonstrated that
      immunocontraception was effective in possums and that oral delivery in edible
      plant material might be possible. Nuclear transformation with reporter genes
      showed that transgenic carrot roots accumulate high levels of foreign protein in
      edible tissues, indicating their potential as a delivery vector. However, prior
      to attempts at large scale production, more effective immunocontraceptive antigen
      adjuvant formulations are probably required before plant-based
      immunocontraception can become a major tool for immunocontraceptive control of
      overabundant vertebrate pests.

PMID- 15734055
TI  - Virus-like particle expression and assembly in plants: hepatitis B and Norwalk
      viruses.
AB  - Expression of vaccine antigens in plants and delivery via ingestion of transgenic
      plant material has shown promise in numerous pre-clinical animal studies and in a
      few clinical trials. A number of different viral antigens have been tested, and
      among the most promising are those that can assemble virus-like particles (VLP),
      which mimic the form of authentic virions and display neutralizing antibody
      epitopes. We have extensively studied plant expression, VLP assembly, and
      immunogenicity of hepatitis B surface antigen (HBsAg) and Norwalk virus capsid
      protein (NVCP). The HBsAg small protein (S protein) was found by TEM to assemble
      tubular membrane complexes derived from endoplasmic reticulum in suspension
      cultured cells of tobacco and soybean, and in potato leaf and tuber tissues. The
      potato material was immunogenic in mice upon delivery by ingestion. Here we
      describe the plant expression and immunogenicity of HBsAg middle protein (M
      protein or pre-S2 + S) which contains additional 55 amino acid pre-S2 region at N
      terminus of the S protein. Plant-derived recombinant M protein provoked stronger
      serum antibody responses against HBsAg than did S protein when injected
      systemically in mice. We discuss implications for use of fusion proteins for
      enhanced immunogenicity and mucosal targeting of HBsAg, as well as delivery of
      heterologous fused antigens. NVCP expressed in plants assembled 38 nm virion-size
      icosahedral (T = 3) VLP, similar to those produced in insect cells. The VLP
      stimulated serum IgG and IgA responses in mice and humans when they were
      delivered by ingestion of fresh potato tuber. Here we show that freeze-drying of
      transgenic NVCP tomato fruit yielded stable preparations that stimulated
      excellent IgG and IgA responses against NVCP when fed to mice. However, the
      predominant VLP form in tomato fruit was the small 23 nm particle also observed
      in insect cell-derived NVCP.

PMID- 15734056
TI  - The development of a plant-based vaccine for measles.
AB  - Plant-based vaccination strategies have the potential to overcome the limitations
      of the current measles vaccine. The measles virus hemagglutinin (MV-H) protein
      has been expressed in tobacco. Oral immunisation of mice with plant-derived MV-H
      protein resulted in MV-specific antibodies and secretory IgA, indicative of
      humoral and mucosal immune responses. In addition, boosting with oral plant
      derived MV-H protein following a MV-H DNA prime, resulted in a greater response
      than could be induced with either vaccine alone. Collectively, this research
      represents a significant step towards an effective oral measles vaccine that
      would be temperature-stable, easy to administer and amenable to inexpensive
      manufacture.

PMID- 15734057
TI  - Plant-derived vaccines against diarrheal diseases.
AB  - Transgenic plants present a novel system for both production and oral delivery of
      vaccine antigens. Production of protein antigen in food plants is substantially
      cheaper than production in bacterial, fungal, insect cell, or mammalian cell
      culture. Edible plants themselves can also serve as the oral vaccine delivery
      system. Phase-1 studies of raw transgenic potatoes expressing the B subunit of
      Escherichia coli heat labile enterotoxin (LT-B), potatoes expressing Norwalk
      virus capsid protein, and defatted corn germ meal expressing LT-B have been
      conducted. New oral vaccines based on other transgenic plants will soon be
      evaluated in humans.

PMID- 15734058
TI  - Challenges in creating a vaccine to prevent hepatitis E.
AB  - Recombinant hepatitis E virus capsid protein (HEV CP) assembles orally
      immunogenic virus-like particles (VLP) when expressed in an insect cell system.
      We used plant expression cassettes, pHEV101 and pHEV110, for transformation of
      potato to express HEV CP, and 10 independent transgenic lines of HEV101 and 6
      lines of HEV110 were obtained. ELISA for HEV CP was performed on tuber extracts.
      Accumulation of HEV CP in tubers varied from about 5 to 30 microg/g fresh tuber
      depending on the transgenic plant line. We further compared the expression levels
      with the yield of tubers for each line. Tuber yield varied less than expression
      levels, and ranged from about 600 to 1000 g per pot. Although Western blot showed
      that apparently intact HEV CP accumulated, we observed very limited assembly of
      virus-like particles in potato tubers. Oral immunization of mice with transgenic
      potatoes failed to elicit detectable anti-CP antibody response in serum,
      suggesting that VLP assembly is a key factor in orally delivered HEV CP vaccines.

PMID- 15734059
TI  - Plant based HIV-1 vaccine candidate: Tat protein produced in spinach.
AB  - The HIV-1 Tat protein has been recently explored as a prospective vaccine
      candidate with broad, subtype non-specific action. We approached the problem of
      delivery of Tat through the mucosal route by expressing Tat in an edible plant.
      The tat gene was assembled from synthetic overlapping oligonucleotides, and was
      subsequently cloned into a plant virus-based vector tobacco mosaic virus (TMV).
      Spinach plants inoculated with the Tat-producing constructs were collected and
      fed to mice 7-14 days post inoculation. DNA vaccinations were performed using a
      gene gun. Codon optimization of the Tat gene expressed in spinach plants resulted
      in several-fold yield increase as detected in immunoblots, and did not cause
      severe symptoms in inoculated plants. Mice were fed with the Tat-producing or
      control vector-inoculated spinach. After three feedings, 1 week apart, 1g per
      mice, no differences were detected in the growth rate or behavior of the animals
      fed with these three types of spinach. None of the animals developed measurable
      Tat antibodies. Following DNA vaccination, however, mice having previously
      received oral Tat developed higher antibody titers to Tat than did the controls,
      with the titers peaking at 4 weeks post-vaccination. Codon optimization allows
      production of up to 300-500 microg of Tat antigen per 1 g of leaf tissue in
      spinach using a plant virus-based expression system. The plant produced Tat does
      not seem to have any apparent adverse effect on mice growth or behavior, when fed
      with spinach for 4 weeks. ELISA data suggested that oral Tat primed for the
      development of Tat antibodies when mice were subsequently vaccinated with plasmid
      DNA designed for Tat expression.

PMID- 15734060
TI  - Cultivating fertile ground for the introduction of plant-derived vaccines in
      developing countries.
AB  - Like any biotechnology innovation, the production of human vaccines in plants
      will succeed partly on its technical merits, and partly on the social acceptance
      of the new technology. The latter is harder to predict than the former, and may
      pose the most significant challenges to plant-derived vaccines' (PDVs) success.
      To realize the potential benefits of plant-derived vaccines, especially for
      developing countries in which health inequities are most acute, social challenges
      must be anticipated and addressed in a way that will foster concrete policy
      alternatives. The ultimate aim is to minimize the risk of premature social
      rejection of plant-derived vaccines.

PMID- 15734062
TI  - Fast track selection of immunogens for novel vaccines through visualisation of
      the early onset of the B-cell response.
AB  - A most essential step in vaccine research and development, ie vaccine studies in
      animals, seriously suffer from long timespans needed to arrive at effective
      immunogens. In this report we show how almost immediately after vaccination the
      antibody inducing potential of low immunogenic 'self' antigens can be accurately
      assessed. (We expect that this timespan can be reduced even more when 'non self'
      antigens are used, since such responses should be stronger.) The method takes
      advantage of the immediate onset after vaccination of the immune response in the
      spleen. This novel method allows detection of antigen-specific B cells of the
      spleen as early as 7 days after immunization and at frequencies as low as 10 in
      1,000,000 cells. The method depends on sequential staining with PE- and APC
      conjugated tetramers, made with the same biotinylated peptide. The antigenic
      peptides are biotinylated and tetramerized with either PE neutravidin or APC
      streptavidin. We expect that this method can be generally applied to visualize B
      cell responses, irrespective of the way they are induced. In addition to the fast
      selection and development of novel immunogens, this procedure can be used to
      delineate the kinetics of the B cell response, to phenotypically characterize and
      to isolate antigen-specific B cells, and, perhaps most importantly, to count them
      at the clonal level before any circulating antibodies can be detected.

PMID- 15734061
TI  - Size determination of bacterial capsular oligosaccharides used to prepare
      conjugate vaccines against Neisseria meningitidis groups Y and W135.
AB  - The glycoconjugate vaccines against Neisseria meningitidis groups Y and W135
      consist of pools of selected oligosaccharides conjugated to the protein carrier
      (CRM197). Consistent production of these vaccines requires control and thus
      determination of the average degree of polymerisation of the oligosaccharides
      used for conjugation. Acid hydrolysis generates group Y and W135 oligosaccharides
      with N-acetylneuraminic acid at the reducing end. A method, involving NaBH4
      reduction and quantification of this terminal N-acetylneuraminic acid by use of
      high performance anion-exchange chromatography with pulsed amperometric detection
      (HPAEC-PAD) following acid hydrolysis (2M TFA), was developed. The average degree
      of polymerisation is calculated from the ratio of reduced N-acetylneuraminic acid
      to total N-acetylneuraminic acid. The assay was qualified by application to group
      C, Y and W135 oligosaccharide standards characterised by liquid chromatography,
      mass and NMR spectroscopy.

PMID- 15734063
TI  - Impact of plasmid supercoiling on the efficacy of a rabies DNA vaccine to protect
      cats.
AB  - As of today, most DNA vaccination trials have been performed with plasmid
      preparations highly enriched in supercoiled molecules (sc) and the importance of
      supercoiled versus open circular (oc) plasmid isoforms for vaccine immunogenicity
      has only received limited attention. This study demonstrated that a single rabies
      DNA vaccination fully protected cats against a lethal rabies challenge as early
      as 3 weeks post vaccination provided that the proportion of supercoiled isoform
      in the vaccinal solution is at least 48%. In contrast, vaccination with a plasmid
      containing only 20% of supercoiled molecules induced significant but only partial
      protection. Further, a single rabies DNA vaccination with plasmids containing at
      least 70% of supercoiled molecules triggered statistically significant specific
      antibody titers and specific Th-1 oriented cell-based immunity as early as 2 and
      3 weeks post vaccination, respectively. It is concluded that the oc isoforms are
      less efficient than supercoiled isoforms at inducing a complete profile of immune
      responses. Therefore, it is proposed that the target threshold of supercoiling
      that must be met by a rabies DNA vaccine to guarantee optimal immune responses
      and protection, be set at 70% of supercoiled molecules in the vaccine solution.

PMID- 15734064
TI  - Comparative immunomodulatory properties of a chitosan-MDP adjuvant combination
      following intranasal or intramuscular immunisation.
AB  - As the precise functions of adjuvants become clearer, opportunities are presented
      in their complementary use for the induction of tailored immune responses to
      subunit vaccines. Here we comparatively investigate the immunological outcome
      following intranasal or intramuscular immunisation with Helicobacter pylori
      urease admixed to a chitosan and muramyl di-peptide (MDP) combination. MDP
      appeared to limit the antigenicity of rUre by either administration route. Nasal
      administration of the combined adjuvant formulation resulted in an up-regulation
      of type I recall responses in splenocytes as opposed to adjuvantisation with
      chitosan alone. In contrast, intramuscular immunisation appeared to limit the
      responsiveness to the antigen when adjuvanted with chitosan and even more so when
      chitosan was combined with MDP, suggesting that the mechanism of adjuvantisation
      and adjuvant synergy differed depending on the immunisation route. Recognising
      the benefit of improved delivery of MDP intranasally due to the specific
      physiological effects of chitosan, we discuss the impact of the newly identified
      pathogen associated molecular pattern (PAMP) role of MDP with respect to the
      adjuvanticity of proposed chemical variants of this peptide adjuvant.

PMID- 15734065
TI  - VP22 enhances antibody responses from DNA vaccines but not by intercellular
      spread.
AB  - In some species DNA vaccines elicit potent humoral and cellular immune responses.
      However, their performance in humans and non-human primates is less impressive.
      There are suggestions in the literature that an increase in the intercellular
      distribution of protein expressed from a DNA vaccine may enhance immunogenicity.
      We incorporated the Herpes Simplex Virus type 1 (HSV) VP22 gene, which encodes a
      protein that has been described as promoting intercellular spread, into a DNA
      vector in which it was fused to enhanced green fluorescent protein (EGFP).
      Following transfection of the plasmid DNA into mammalian cells, distribution of
      the fusion protein VP22-EGFP was not increased compared to EGFP alone.
      Furthermore, we found no evidence to suggest that VP22 was capable of mediating
      intercellular spread. However, when these constructs were used as DNA vaccines to
      immunise mice, antibody levels specific to EGFP were significantly enhanced when
      EGFP was fused to VP22. These data suggest that amplification of the immune
      response may occur via mechanisms other than VP22-mediated intercellular spread
      of antigen.

PMID- 15734066
TI  - To vaccinate or not to vaccinate--that is the question: why are some mothers
      opposed to giving their infants hepatitis B vaccine?
AB  - OBJECTIVE: To identify the characteristics of mothers who prevent their newborn
      babies from receiving the hepatitis B vaccine. METHODS: Women who gave birth and
      prevented the administration of routine hepatitis B vaccine to their newborn
      infants (study group) were compared to women who complied with vaccination
      (control group). During their hospital stay, both groups were asked to answer a
      questionnaire constructed to evaluate relevant demographic data, knowledge and
      attitudes liable to differ between the two groups. RESULTS: The 51 women in the
      Prevent (study) group were more educated and had a higher income level. They
      expressed more knowledge about the vaccine, and held more naturalistic and less
      conventional medical attitudes than did the women in the Comply (control) group
      (153 women). Some of the reasons given by the Prevent group for vaccine rejection
      included the following: "The child is too young"; "vaccines are dangerous";
      "Doctors vaccinate without consideration"; "Vaccines causes trauma to the baby".
      The Comply group's reasons for giving the vaccine were mainly "to protect the
      baby" and "trust in the doctors". Differences between the groups were also found
      with respect to their future intended behavior. The study group planned to
      breastfeed for a longer period than the control group. Only 16% of the study
      group compared to 98% of the control group stated they intended to comply with
      the full vaccination program offered to developing children. On the basis of the
      answers to the questionnaire, the Comply group was further subdivided into two
      groups: those with knowledge and those lacking knowledge (determined by
      subjective evaluation). This subdivision showed that the differences between the
      Prevent Group and the Comply group exist, even though knowledge was controlled
      for. CONCLUSIONS: Mothers prevent administration of the hepatitis B vaccine to
      their newly born children based upon their overall approach, and not due to
      ignorance. In order to overcome this harmful trend, the medical community must
      supply counter information that encourages vaccinations.

PMID- 15734067
TI  - Subtype AE HIV-1 DNA and recombinant Fowlpoxvirus vaccines encoding five shared
      HIV-1 genes: safety and T cell immunogenicity in macaques.
AB  - To induce broad T cell immunity to HIV-1, we evaluated the safety, immunogenicity
      and dose-response relationship of DNA and recombinant Fowlpoxvirus (rFPV)
      vaccines encoding five shared HIV subtype AE genes (Gag, Pol, Env, Tat, Rev) in
      pigtail macaques. The DNA (three doses of either 1 mg or 4.5 mg) and rFPV (a
      single boost of either 5 x 10(7) or 2 x 10(8) plaque forming units) vaccines were
      administered intramuscularly without adjuvants. Broadly reactive HIV-specific T
      cell immunity was stimulated by all doses of the vaccines administered, without
      significant differences between the high and low doses studied. The vaccines
      induced both CD4 and CD8 T cell responses to Gag, Pol, Env and Tat/Rev proteins,
      with CD4 T cell responses being greater in magnitude than CD8 T cell responses.
      The vaccine-induced T cell responses had significant cross-recognition of
      heterologous HIV-1 proteins from non-AE HIV-1 subtypes. In conclusion, these
      subtype AE HIV-1 DNA and rFPV vaccines were safe, induced broad T-cell immunity
      in macaques, and are suitable for progression into clinical trials.

PMID- 15734068
TI  - Effect of homologous and heterologous prime-boost on the immune response to
      recombinant plague antigens.
AB  - Among the pathogens that have been identified as potential agents of biological
      warfare or bioterrorism, Yersinia pestis is one of the main concerns due to the
      severity and potential transmissibility of the pneumonic form of the disease in
      humans. There are no approved vaccines for protection against pneumonic plague,
      but a Y. pestis-derived fusion protein (F1-V) has shown great promise as a
      protective antigen in murine studies. In the current study, we examine different
      prime-boost regimens, including parenteral, mucosal, and transcutaneous delivery,
      in order to explore the effect of changing the route of prime and boost on the
      ability of recombinant F1-V to promote the development of long-lasting, high
      titer antibodies. The most significant findings of the study reported here are
      that (1) intranasal and subcutaneous immunizations are both effective and
      essentially equivalent for induction of serum and bronchioalveolar anti-F1-V IgG1
      responses when a single booster dose is administered by the same (homologous)
      route, (2) heterologous boosting can be as or more effective than homologous
      boosting for induction of either serum or bronchioalveolar anti-F1-V IgG1
      responses, and (3) anti-F1 and anti-V total IgG responses were highest in animals
      primed intranasally and boosted by any route when compared to animals primed
      transcutaneously or subcutaneously. As with previously published studies, there
      were still significant levels of circulating anti-F1-V antibodies 1 year post
      primary immunization. These studies provide important insights into the
      development of new-generation biodefense vaccines.

PMID- 15734069
TI  - Antigen epitope-expressing cytokines for DNA immunization.
AB  - Strategies to enhance the efficacy of DNA vaccination against malignancy remain
      to be established. In this study, a plasmid expressing a tumor antigen
      incorporated into the signal peptide of human IL-2 was tested as a DNA vaccine in
      a murine model system. Results showed that antigen-specific CTL responses were
      elicited by intramuscular injection of these plasmids. Importantly, compared with
      a minigene vector expressing the same epitope, the OVA epitope-incorporated, IL-2
      expression plasmid vaccination was more effective in protecting mice from OVA
      expressing tumor challenge. The improved efficacy appears to result from enhanced
      antigen presentation as well as the immunostimulatory activity of IL-2. This
      approach may provide new perspectives in designing cytokine-adjuvant DNA vaccines
      for clinical applications.

PMID- 15734070
TI  - Economic evaluation of vaccination against influenza in the elderly: an
      experience from a population-based influenza vaccination program in Taiwan.
AB  - Due to viral strains, influenza season, and consultations and admission rates
      varying from country to country, the continued economic evaluation of influenza
      vaccination for the elderly people aged 65 years and above is paramount,
      particularly in areas with dense population. Efficacy and cost-effective analysis
      of influenza vaccination in reducing all-cause mortality and hospitalization was
      therefore elucidated based on a prospective and population-based study targeted
      to 226,997 elderly people aged 65 years and above residing in Taipei county,
      Taiwan between 1 October 2000 and 31 March 2001. Vaccination against influenza
      for the elderly persons can lead to a 29% (95% CI: 23-35%) significant reduction
      of all-cause deaths. Approximately, 20% (95% CI: 9-30%) significant reduction in
      hospitalization was observed for average-risk group but 4% (95% CI: -4-11%) non
      significant reduction for high-risk group. Community-based influenza vaccination
      program for elderly people aged 65 years and above was demonstrated to be
      effective in reducing mortality in all elderly people but not significantly in
      reducing hospitalization. Universal vaccination program for the elderly people
      seems cost-effective in averting death or gaining life years.

PMID- 15734071
TI  - Effectiveness of the 2003-2004 influenza vaccine among U.S. military basic
      trainees: a year of suboptimal match between vaccine and circulating strain.
AB  - Effectiveness of the 2003-2004 influenza vaccine was evaluated at five military
      basic training centers throughout the United States. Data from surveillance
      conducted in December and January 2003-2004 in this highly vaccinated population
      were evaluated. During this period, 10.6% (37/350) of specimens were positive for
      influenza A. A 14-day period after vaccination was considered the period prior to
      immune protection; vaccine effectiveness (VE) was calculated based on febrile
      respiratory illness presentation and laboratory confirmation of influenza before
      or after this 14-day period. Thirty-two cases presented within 14 days of
      vaccination, and five cases presented beyond 14 days from vaccination. VE in this
      population was estimated to be 94.4% for laboratory-confirmed influenza. In
      contrast, VE was only 13.9% for influenza-like illness (ILI) without a laboratory
      confirmation.

PMID- 15734072
TI  - Aerogenic vaccination with a Burkholderia mallei auxotroph protects against
      aerosol-initiated glanders in mice.
AB  - Burkholderia mallei is an obligate mammalian pathogen that causes the zoonotic
      disease glanders. Two live attenuated B. mallei strains, a capsule mutant and a
      branched-chain amino acid auxotroph, were evaluated for use as vaccines against
      aerosol-initiated glanders in mice. Animals were aerogenically vaccinated and
      serum samples were obtained before aerosol challenge with a high-dose (>300 times
      the LD50) of B. mallei ATCC 23344. Mice vaccinated with the capsule mutant
      developed a Th2-like Ig subclass antibody response and none survived beyond 5
      days. In comparison, the auxotrophic mutant elicited a Th1-like Ig subclass
      antibody response and 25% of the animals survived for 1 month postchallenge.
      After a low-dose (5 times the LD50) aerosol challenge, the survival rates of
      auxotroph-vaccinated and unvaccinated animals were 50 and 0%, respectively. Thus,
      live attenuated strains that promote a Th1-like Ig response may serve as
      promising vaccine candidates against aerosol infection with B. mallei.

PMID- 15734073
TI  - Immunogenicity in mice of anthrax recombinant protective antigen in the presence
      of aluminum adjuvants.
AB  - The only US-licensed anthrax vaccine for human use, as well as several
      experimental vaccines containing solely purified recombinant protective antigen
      (rPA), are formulated using aluminum hydroxide (Al(OH)3) as an adjuvant. It has
      been suggested that effective adjuvanticity of aluminum salts for protein
      antigens depends, at least partially, on the degree of adsorption of the antigen
      to the adjuvant. On the other hand, the ease of antigen desorption from the
      adjuvant in a quantitative fashion may facilitate the assessment of vaccine
      characteristics in the laboratory. In this regard, aluminum phosphate (AlPO4),
      although deemed a "weaker" adjuvant than Al(OH)3, appears superior to the latter.
      To investigate the possibility of formulating rPA vaccines with AlPO4, as well as
      the significance of the adsorption of this antigen to the aluminum salt for
      adjuvanticity, we studied the effect of AlPO4 and Al(OH)3 on the induction of
      anti-rPA antibodies in mice. In a first immunization experiment the adjuvanticity
      of AlPO4 combined with rPA was examined. Antibodies against rPA were measured
      using an ELISA. Results indicated that AlPO4 is able to significantly increase
      the antibody response to rPA, irrespective of its degree of adsorption to the
      adjuvant. Based on these results, in a second experiment mice were immunized
      twice, with different formulations of rPA containing either AlPO4 or Al(OH)3, and
      rPA-antibodies were measured using ELISA and an in vitro toxin neutralization
      assay. Comparable immune responses to rPA were obtained with both aluminum salts.
      Additionally, results with AlPO4 as adjuvant confirmed that, in this mouse model,
      binding of the protein to the adjuvant is not essential for adjuvanticity,
      whereas the amount of adjuvant has an influence on the antibody response induced.

PMID- 15734074
TI  - Moraxella catarrhalis strains with reduced expression of the UspA outer membrane
      proteins belong to a distinct subpopulation.
AB  - The outer membrane proteins UspA1 and UspA2 are candidate antigens for a
      Moraxella catarrhalis vaccine. We previously reported that 103 of 108 isolates
      (95%) from young children expressed UspA1 detected by reactivity with the
      monoclonal antibody mAb24B5. The aim of the present study was to investigate
      mechanisms controlling UspA1 expression by analysis of five mAb24B5 non-reactive
      isolates. Four of these strains were characterized by (i) decreased or absent
      transcription of uspA1 and uspA2 and (ii) clustered mutations and deletions in
      the promoter region of both uspA1 and uspA2. Antigenic or phase variation were
      not responsible for reduced levels of UspA1 expression. While mAb24B5-positive
      isolates expressing normal levels of uspA1 and uspA2 mRNA belonged to the
      previously described 16S rRNA type 1 phylogenetic group, these four mAb24B5
      negative isolates were found to belong to the 16S rRNA gene types 2 or 3. The
      remaining mAb24B5-negative isolate (#610) belonged to 16S rRNA type 1 and
      exhibited a posttranscriptional defect of UspA1 expression defined by normal
      levels of uspA1 mRNA and both recombinant and in vitro expression of mAb24B5
      reactive UspA1. In conclusion, M. catarrhalis clinical isolates exhibiting
      reduced expression of UspA1 and UspA2 belonged to a distinct phylogenetic
      subpopulation. A UspA-based vaccine is unlikely to be effective against such
      isolates.

PMID- 15734075
TI  - Description of the immunization information database: a tool for investigating
      allegations made against childhood immunizations.
AB  - This paper describes the Immunization Information Database (IID). The IID is
      designed for cataloguing and systematically analyzing allegations that give rise
      to public concern regarding the safety, efficacy, and appropriateness of routine
      childhood immunizations. We describe the IID's eight data tables (Immunization
      Type; Claim; Claim Basis; Claimant; Source Documentation; Source Type; Claim
      Analysis; and Claim Analysis Type), and explain how these tables function to
      create a conceptual map of existing allegations.

PMID- 15734076
TI  - Seroprevalence and immunization history of selected vaccine preventable diseases
      in medical students.
AB  - To evaluate protection against vaccine-preventable diseases in medical students,
      we obtained data on immunization status and history of diphtheria, tetanus,
      pertussis, poliomyelitis, measles, mumps, rubella, varicella and hepatitis B from
      students with elective periods in our institution. Further, serum antibodies
      against measles, mumps, rubella and varicella-zoster virus (VZV) and hepatitis B
      surface (HBs) antigen were determined on a voluntary basis. For students with
      incomplete immunization status or lack of protective antibodies, vaccination was
      offered for free. Success of catch-up immunizations was serologically confirmed 4
      weeks later. From May 1999 to April 2003, 170 students were enrolled; their mean
      age was 26 years with a median of 25 years (range 22-48 years). Immunization
      records were complete in 148 (87%), incomplete in 11 (6.5%) and missing in 11
      (6.5%) students. Only 26% of the cohort had a complete and up-to-date
      immunization status. Seroprevalence of IgG antibodies against measles, mumps,
      rubella, VZV and HBs (> or = 10 IU/l) in 149 students were 85, 85, 92, 97 and
      90%, respectively. Indications for > or = 1 catch-up immunization were found in
      125 (74%) students and were accepted by 97 of them (78%). Sixty two (99%) of 63
      immunized students available for follow-up demonstrated an adequate serological
      response. In conclusion, the great majority of medical students had immunization
      gaps. Systematic immunization programmes for medical students should be
      implemented.

PMID- 15734078
TI  - Fertility and pregnancy in women with psychotic disorders.
AB  - The majority of women with psychotic disorders have children but their
      pregnancies are at an increased risk of obstetric and psychiatric complications.
      This paper reviews research into the fertility of women with psychosis and
      complications occurring during their pregnancies and in the postpartum period.
      Mesh terms were used to search electronic databases (Medline, Embase, Psychlit
      and the Cochrane database of systematic reviews). Recent studies have confirmed
      earlier findings of a low fertility in women with schizophrenia, though fertility
      is less affected by mood disorders. Psychotic relapse during pregnancy is rare
      but women with a history of mood disorders (affective psychoses) are at high risk
      of postpartum relapse. There is a high risk of obstetric complications, mixed
      evidence of stillbirths and neonatal deaths and there is some weaker evidence of
      an association with sudden infant death syndrome. A significant proportion of
      mothers with psychotic disorders have parenting difficulties and lose custody of
      their infant. Close liaison between all health professionals during pregnancy and
      postpartum is essential for optimal management of these high risk pregnancies.

PMID- 15734079
TI  - The accuracy of maternal anthropometry measurements as predictor for spontaneous
      preterm birth--a systematic review.
AB  - OBJECTIVE: To assess the accuracy with which antenatal maternal anthropometric
      measurements predict the risk spontaneous preterm birth. STUDY DESIGN: (1) DATA
      SOURCES: Studies were identified without language restrictions from MEDLINE,
      EMBASE, PASCAL, BIOSIS, the Cochrane Library, MEDION, National Research Register,
      SCISEARCH and Conference Papers, and manual searching of bibliographies of known
      primary and review articles, and contact with authors. (2) STUDY SELECTION AND
      DATA EXTRACTION: Studies were selected if they used antenatal maternal
      anthropometric features (pre-pregnancy weight, maternal pregnancy weight gain and
      maternal height) to predict spontaneous preterm birth. Two reviewers
      independently selected studies and extracted data on their characteristics,
      quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables of
      the maternal anthropometric test results with spontaneous preterm birth as the
      reference standard. (3) DATA SYNTHESIS: Heterogeneity assessments were carried
      out to aid the decision regarding pooling of the accuracy results. Likelihood
      ratios for positive (LR+) and negative (LR-) test results were calculated, and
      summary estimates were produced in absence of heterogeneity of the accuracy
      results. RESULTS: There were eight primary accuracy articles that met the
      selection criteria, which included a total of 122,647 asymptomatic women. There
      were six studies on pre-pregnancy weight where five measured the body mass index
      (BMI) and one used an arbitrary measure. There were four studies on the adequacy
      of pregnancy weight gain and two studies on maternal height as a predictor for
      the risk of preterm birth. One article contributed three studies, while two
      articles provided two studies each. The commonest reference standard used was
      birth before 37 weeks' gestation. None of the studies fulfilled the ideal test
      accuracy study criteria. There was heterogeneity in the accuracy results of pre
      pregnancy BMI but not in the adequacy of weight gain. All three maternal
      anthropometric features were poor predictors of preterm labour. Pre-pregnancy BMI
      is a poor predictor of preterm birth before 37 weeks' gestation (LR+ that ranged
      from 0.96 (95% confidence interval (CI) 0.66-1.40) to 1.75 (95% CI 1.33-2.31)) as
      are the adequacy of pregnancy weight gain (summary LR+ of 1.81, 95% CI 1.45-2.30)
      and short maternal height (LR+ of 1.79 (95% CI 1.27-2.52). CONCLUSION: Routine
      antenatal maternal anthropometric measurements are not useful in predicting the
      risk of preterm birth before 37 weeks' gestation. Further studies should address
      their use in combination with other test but need to use a more clinically
      appropriate reference standard of preterm birth, such as birth before 32-34
      weeks' gestation, and improve on the quality of study design.

PMID- 15734080
TI  - Effect of amoxicillin sulbactam in threatened preterm labour with intact
      membranes: a randomised controlled trial.
AB  - OBJECTIVE: To determine whether treatment with amoxicillin-sulbactam in women
      with threatened idiopathic preterm labour will prolong the gestation and reduce
      preterm birth rates in a Latin-American population. METHODS: A double-blind,
      placebo-controlled, randomized trial was conducted in 96 women who were
      hospitalized for preterm labour between 24 and 34 weeks of gestation at the
      Pereira Rossell Hospital, in Montevideo, Uruguay. The primary outcome measure was
      prematurity. The sample size was calculated a priori based on the hospital
      database. Statistical analyses were performed using the t-test, chi square,
      weighted mean difference (WMD) and relative risk (RR) with their confidence
      intervals (95% CI). Analysis by intention-to-treat. RESULTS: Out of 47 patients
      assigned for antibiotics, 43 completed the treatment. There were no significant
      statistical differences between antibiotics and placebo group in prematurity
      (RR:1.04, 95% CI: 0.59, 1.84), prolongation of pregnancy (WMD:0.23, 95% CI: 
      0.96, 1.42) and other perinatal outcomes. CONCLUSION: Antibiotics did not prove
      to have benefits in improving perinatal outcomes in this Latin American
      population.

PMID- 15734081
TI  - Fibroblast growth factor-10 and fibroblast growth factor receptors 1-4:
      expression and peptide localization in human decidua and placenta.
AB  - The development of the chorionic villous tree into a complex and organized
      ramified tubular network can be termed branching morphogenesis. Studying the
      molecular mechanisms involved in this process may contribute to the understanding
      of pregnancy complications such as preeclampsia. We hypothesized that fibroblast
      growth factor-10 (FGF-10) and fibroblast growth factor receptors 1-4 (FGFR 1-4)
      are expressed in human decidual and placental tissues. We analyzed the expression
      of FGF-10 and FGFRs 1-4 in 1st, 2nd and 3rd trimester placentas, as well as in
      decidua. RT-PCR and immunohistochemistry were employed to study mRNA and protein
      expression. FGF-10 was expressed by decidual cells and by cytotrophoblasts of the
      cytotrophoblast columns during all three trimesters. FGFR 1-4 were expressed in
      the placenta but not in the decidua. Placental expression of FGFRs was temporally
      regulated: In 1st trimester placentas, FGFR 1-4 were expressed by Hofbauer cells,
      FGFR-1 and FGFR-4 were expressed in cytotrophoblast columns, and the latter was
      also expressed by syncytiotrophoblasts. Similar expression was seen in 2nd
      trimester placentas with additional expression of FGFR-1 in blood vessel walls.
      The expression of FGFR-1 and FGFR-4 in the 3rd trimester was comparable to that
      seen in the 2nd trimester. The expression of FGF-10, FGFR-1 and FGFR-4 in the
      maternal-fetal interphase suggests their role in decidual-trophoblast
      interaction. The abundance of FGFR expression in Hofbauer cells implies that
      mesenchymal-trophoblast interaction is important for regulation of villous
      development.

PMID- 15734082
TI  - Are plasma total homocysteine and other amino acids associated with glucose
      intolerance in uncomplicated pregnancies and preeclampsia?
AB  - OBJECTIVE: To evaluate the possible association between plasma total homocysteine
      or other amino acid concentrations and gestational diabetes or glucose
      intolerance (GI), in normotensive and preeclamptic pregnant women. STUDY DESIGN:
      Prospective study including 243 pregnant women without previous risk factors.
      O'Sullivan test (plus oral glucose tolerance test when necessary) was performed,
      and homocysteine, B vitamins and plasma amino acids (AA) were measured at 24-25
      weeks. Homocysteine and other amino acids were also measured in the third
      trimester. RESULTS: Significant differences were observed in the incidence of
      preeclampsia in relation to abnormal glucose tolerance (P < 0.012). In
      normotensive patients, the glucose intolerance group showed significantly lower
      tHcy (P = 0.021) and increased plasma alanine concentrations in comparison with
      controls (P = 0.046), although no correlation was observed between both amino
      acid concentrations. CONCLUSIONS: (a) A higher incidence of preeclampsia was
      observed in abnormal glucose tolerance patients, (b) total homocysteine and
      alanine were the only individual amino acids whose plasma concentrations varied
      according to the glucose tolerance classes, and (c) an association between
      hyperhomocysteinemia and glucose intolerance in our preeclamptic patients could
      not be demonstrated.

PMID- 15734083
TI  - Oxidative stress-related gene polymorphism and the risk of preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine whether genetic variability
      in oxidative stress-related enzymes contributes to individual preeclampsia
      susceptibility differences. STUDY DESIGN: Polymorphisms in the cytochrome P450
      (CYP)1A1 (MspI), CYP1A1(Ile/Val), glutathione S-transferase (GST)M1, GSTT1,
      myeloperoxidase (MPO), and manganese superoxide dismutase (MnSOD) genes were
      evaluated by polymerase chain reaction (PCR) or PCR-restriction fragment length
      polymorphism (RFLP) in 214 healthy controls with an uncomplicated obstetric
      history, and in 121 preeclampsia patients. Chi2 analyses were used to
      statistically evaluate differences. RESULTS: No significant differences in the
      CYP1A1(MspI) or CYP1A1(Ile/Val) genotypes were observed between the healthy
      controls and the preeclampsia patients (chi2 = 1.43, P = 0.49 versus chi2 = 1.54,
      P = 0.46). The GSTM1 homozygous null type and GSTT1 homozygous null type were no
      differences in the patients and controls (chi2 = 0.01, P = 0.92 versus chi(2) =
      0.31, P = 0.57), and no significant differences in the polymorphisms of the MPO
      and MnSOD genotypes were found between the patients and controls (chi2 = 2.00, P
      = 0.37 versus chi2 = 0.07, P = 0.96). CONCLUSION: Polymorphisms in the oxidative
      stress-related genes (CYP1A1, GSTM1, GSTT1, MPO, MnSOD) do not seem to be risk
      factors for preeclampsia.

PMID- 15734084
TI  - Prevalence of cranial scan abnormalities in preterm twins in relation to
      chorionicity and discordant birth weight.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of
      ultrasonographically detected cerebral white matter lesions (WMLs) in preterm
      twins at birth in relation to chorionicity, discordant weight and twin-twin
      transfusion syndrome (TTTS). METHODS: In this retrospective study, perinatal,
      neonatal, and cranial scan data of 85 monochorionic (MC) and 94 dichorionic (DC)
      twin pregnancies (341 infants) delivered between 24 and 34 weeks of gestation
      were collected. Data were analysed according to chorionicity, discordant birth
      weight (>20%), single intrauterine death and TTTS. RESULTS: The cerebral WML was
      seen in 14% of preterm twins. Monochorionic infants had higher risks of WML than
      DC twin (odds ratio 7.1; 95% CI 3.28-15.8). In MC group, discordant weight (37%),
      TTTS (38%), single intrauterine death (67%) had higher incidence of cerebral WML
      than concordant weight infants (7%). Similarly, incidence of WML was higher in DC
      discordant compared with concordant weight infants (13% versus 2%; P < 0.05).
      CONCLUSION: Monochorionic infants had a seven-fold higher incidence of cerebral
      WML than DC infants. Discordant birth weight, TTTS and survivor of co-twin demise
      are an independent risk of cerebral white matter lesion.

PMID- 15734085
TI  - Clinical consequences of first-trimester growth discordance in twins.
AB  - OBJECTIVES: To evaluate the clinical consequences of size discordance in the
      first-trimester of pregnancy in twins. STUDY DESIGN: This study was performed in
      a university tertiary referral centre. Nineteen pairs of twins identified as
      discordant were compared with 41 concordant twins. The rates of intrauterine
      growth restriction (IUGR), congenital malformations, and growth discordance in
      late pregnancy and at delivery were compared using chi-squared test and Fisher's
      exact test. RESULTS: There was not a significant difference in the rate of
      congenital malformations between the studied groups. The rates of IUGR and fetal
      growth discordance in late pregnancy were significantly higher in the first
      trimester discordant group (57.2 and 35.7%, respectively) than in the control
      group (24.4 and 7.3%; P = 0.03 and 0.02, respectively). CONCLUSIONS: First
      trimester growth discordant twins have an increased risk of IUGR and growth
      discordance in late pregnancy, and therefore they are a high-risk subgroup among
      multiple pregnancies.

PMID- 15734086
TI  - Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels
      in preeclampsia.
AB  - OBJECTIVE: To investigate the changes in enzyme activities of erythrocyte
      superoxide dismutase (SOD), catalase, and placental glutathione peroxidase (GSH
      Px), and analyze the levels of serum malondialdehyde (MDA), copper (Cu), zinc
      (Zn), selenium (Se), leptin and placental MDA and glutathione (GSH). STUDY
      DESIGN: Cross-sectional prospective study consisting of 32 preeclamptic (PE)
      pregnant, 25 non-pregnant (NP) women, 28 healthy pregnant (HP) women. Levels of
      lipid peroxides in serum and placenta, and activities of SOD, catalase in
      erythrocyte and placental GSH level, placental GSH-Px activity were measured by
      spectrophotometric methods. Serum levels of Cu, Zn, Se measured by atomic
      absorption spectrophotometry. Serum levels of leptin was measured by enzyme
      immunoassay by using the Cayman chemical kit. One-way analysis of variance and
      post hoc Tukey-HSD test and Pearson correlation test were used for the
      statistical analyses. RESULTS: Serum levels of MDA, Cu, Leptin were markedly
      higher (P < 0.001); and serum level of Se was markedly lower (P < 0.001) in PE
      women compared with HP women and NP women. Also, placental MDA level was higher
      (P < 0.001) and placental GSH-Px activity was lower in PE women compared with HP
      women. In preeclamptic women erythrocyte catalase activity was markedly increased
      (P < 0.001), while erythrocyte SOD activity was markedly decreased (P < 0.001)
      compared to HP women and NP women. Placental GSH level was decreased compared to
      HP women (P < 0.001). Serum level of Zn was markedly decreased compared to NP
      women (P < 0.001) but no significant difference was observed in PE pregnant when
      compared with HP women (P > 0.05). Placental MDA level in PE women had
      significant negative correlation with serum Se level (r = -0.353, P < 0.05). A
      negative correlation was found between erythrocyte catalase activity with birth
      weight (r = -0.528, P < 0.001). Also, there were a significant negative
      correlation between serum levels of Cu and Se in the preeclamptic women (r = 
      0.407, P < 0.05). CONCLUSION: Our data demonstrate that elevation of lipid
      peroxides together with impaired antioxidant defense mechanisms and status of
      trace metals and the presence of possible interrelationship and crosstalk between
      those parameters may be related at least partly to the pathogenesis of
      preeclampsia. Additionally, lipid peroxides and blood oxidative imbalance could
      be part of the cytotoxic mechanisms leading to endothelial cell injury.

PMID- 15734087
TI  - Dietary intake of vitamin C and vitamin E and the development of hypertensive
      disorders of pregnancy.
AB  - OBJECTIVES: To explore the relationship, if any, between dietary intake of the
      antioxidant vitamins C and E, and the development of pre-eclampsia and
      gestational hypertension. STUDY DESIGN: A prospective cohort study of pregnant
      women attending the antenatal clinic of the Women's and Children's Hospital in
      Adelaide, Australia, was carried out between April and July 2001. Women completed
      a semi-quantitative 116-item food frequency questionnaire (FFQ). Women's medical
      records were viewed after birth to collect data on pregnancy outcomes.
      Relationships were explored through cross-tabulations, chi-square analysis, and
      adjustments were made for potential confounders using binary logistic regression.
      RESULTS: A total of 299 women completed the FFQ. Median intake of vitamin C was
      188 mg and for vitamin E was 6.74 mg. There was no relationship between the
      intake of vitamin C and hypertensive disorders of pregnancy. For vitamin E, being
      in the lowest quartile of intake, was associated with an increased risk of
      hypertensive disorders (RR 1.75, 95% CI 1.11-2.75, P = 0.02). This relationship
      was confirmed after adjusting for the confounding factors of maternal age and
      parity. CONCLUSIONS: Little support was found for a relationship between dietary
      intake of vitamin C and the development of hypertensive disorders of pregnancy.
      Low vitamin E intake was associated with a significant increase in the risk of
      hypertensive disorders of pregnancy, even after adjustments were made for
      confounding factors. Further research is required to investigate whether
      supplementation above dietary intake of antioxidant vitamins influences the risk
      of hypertensive disorders of pregnancy.

PMID- 15734088
TI  - Lipid peroxidation in the peritoneal fluid of infertile women with peritoneal
      endometriosis.
AB  - OBJECTIVE: To assess the level of lipid peroxidation in the peritoneal fluid of
      infertile women with peritoneal endometriosis and of fertile disease-free
      controls. STUDY DESIGN: Level of lipid peroxidation (malondialdeyde,
      malondialdeyde with copper addition, and cholest-3,5-dien-7-one) was measured in
      the peritoneal fluid obtained from 21 women with endometriosis-related
      infertility and from 21 fertile women having tubal ligation. RESULTS: : The level
      of lipid peroxidation did not differ significantly (P > 0.05) according to the
      stage of endometriosis. The level of lipid peroxidation (malondialdeyde,
      malondialdeyde with the addition of copper, and cholest-3,5-dien-7-one) did not
      differ significantly (P > 0.05) between patients with endometriosis-related
      infertility (0.07 nmol/ml, 0.34 nmol/ml, 0.24 microg/ml, respectively) and
      disease-free controls (0.04 nmol/ml, 0.21 nmol/ml, 0.25 microg/ml, respectively).
      CONCLUSION: The level of lipid peroxidation did not differ between women with
      endometriosis-related infertility and fertile disease-free controls, suggesting
      that increased reactive oxygen species may not be one of the factors responsible
      for compromised fertility in patients with endometriosis.

PMID- 15734089
TI  - Laparoscopic ovarian drilling in polycystic ovary syndrome.
AB  - BACKGROUND AND OBJECTIVE: Patients with polycystic ovary syndrome (PCOS) treated
      with gonadotrophins often have a polyfollicular response and are exposed to the
      risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. The aim
      of the present study was to evaluate the efficacy of laparoscopic ovarian
      drilling (LOD) on the endocrinologic, clinical parameters and reproductive
      outcome of clomiphene-resistant anovulatory infertile patients with PCOS using
      monopolar diathermy. MATERIAL AND METHODS: Forty-five clomiphene-resistant
      anovulatory women with PCOS have participated in the study. Serum testosterone
      (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH), fasting
      insulin and glucose levels, body mass indexes, modified Ferriman Gallwey (FG)
      hirsutism scores of the subjects are recorded before and after the procedure.
      Endocrinologic and clinical profile and reproductive outcome of the patients were
      analysed. RESULTS: Ovarian drilling was successfully employed without any
      surgical complications and mean +/- S.D. duration of follow-up time was 29.73 +/-
      10.64 months. In the follow-up period 93.3% of the subjects were recorded to have
      regular cycles and 64.4% pregnancy rate was achieved, spontaneously. The serum
      levels of T, free T, LH, LH:FSH ratio, insulin and FG scores were significantly
      reduced after LOD, although glucose levels and glucose/insulin ratio remained
      unchanged. CONCLUSION: In choosing ovulation induction method in clomiphene
      resistant PCOS patients, LOD may avoid or reduce the risk of OHSS and multiple
      pregnancy than gonadotrophins with the same success rate of conception. The high
      pregnancy rate, and economic aspect of the procedure offer an attractive
      management for patients with PCOS.

PMID- 15734090
TI  - Symptom distribution among infertile and fertile endometriosis cases with
      different stages and localisations.
AB  - OBJECTIVE: To evaluate endometriosis patients' symptoms and relate them to
      different stages and locations of endometriosis and also to fertility/infertility
      of the patients. STUDY DESIGN: Sixty-eight patients diagnosed with endometriosis
      constituted the population investigated in this cross-sectional observational
      study, 55 and 13 of whom were diagnosed from the visual findings recorded during
      laparoscopy and laparotomy, respectively. All cases were categorised as early-
      (stages I and II) or late (stages III and IV)-stage endometriosis and as fertile
      or infertile endometriosis. The extent of endometriosis was further divided into
      peritoneal, ovarian, and ovarian and peritoneal. Symptoms of dysmenorrhoea, deep
      dyspareunia, dyschesia and dysuria and also depressive mood state were analysed
      and compared among those different groups. RESULTS: Cyclic chronic pelvic pain
      was more relevant in late-stage endometriosis (P = 0.04). Deep dyspareunia,
      painful defecation, dysuria, infertility, and depressive state did not differ
      with stages of endometriosis or fertility status. Admission for pelvic pain of
      any duration was more prevalent among fertile patients with endometriosis (P =
      0.008). Chronic noncyclic pelvic pain was more frequently observed in patients
      with fertile than in those with infertile endometriosis (P = 0.01). More cases in
      the fertile group experienced noncyclic pelvic pain (P = 0.04). More patients
      admitted with cyclic pelvic pain had ovarian or ovarian and peritoneal
      endometriosis than peritoneal endometriosis only (P = 0.03). Infertility was more
      prevalent among peritoneal endometriosis cases than among those with ovarian or
      peritoneal and ovarian involvement (P = 0.008). CONCLUSION: Symptoms of
      endometriosis may predict the stage and localisation of the disease to some
      extent.

PMID- 15734091
TI  - Evaluation of ovarian functionality after a dietary treatment in obese women with
      polycystic ovary syndrome.
AB  - In women with polycystic ovary syndrome (PCOS) weight loss is associated with an
      improvement in insulin sensitivity and a reduction of the insulin concentration
      in the plasma. It is clear, then, that the first therapeutic approach that can be
      considered in obese PCOS patients for restoration of the menstrual cycle should
      be a diet. The aim of our study was to examine the effect of long-term caloric
      restriction on the clinical and biochemical abnormalities in obese PCOS women.
      The results obtained make it clear that caloric restriction for 4 weeks causes an
      increase in SHBG and decreases of free testosterone and insulin, with consequent
      improvement of the clinical picture.

PMID- 15734092
TI  - Influence of hormonal stimulation on in vitro fertilization/embryo transfer
      outcome.
AB  - OBJECTIVE: To compare efficacy and efficiency of ovarian stimulation therapy.
      STUDY DESIGN: Retrospective study compares ovarian response as number of
      retrieved oocytes, fertilization rates, endometrial patterns, number of
      pregnancies and pregnancy rates to different stimulation protocols. RESULTS: The
      least number of cancelled cycles was in long protocols with buserelin. There was
      no difference in overall number of retrieved oocytes between the rFSH and HMG
      protocols, but 75% of the patients undergoing both protocols had higher number of
      oocytes after rFSH. The highest pregnancy rate (35.13%) was with rFSH. There was
      no statistical correlation between endometrial pattern and type of protocol used.
      Data showed the 9 mm cut-off value for endometrial thickness, and RI = 0.58 for
      subendometrial blood flow between the pregnant and non-pregnant group of
      patients. Nitriderm patches significantly decreased (P < 0.05) subendometrial RI
      of the patients with impaired uterine perfusion, increased endometrial thickness
      and achieved better morphology. CONCLUSIONS: These findings demonstrate that rFSH
      alone and in long protocol gives better results in wide patient population.
      Nitriderm patches seem to have good impact on pregnancy rate, but further studies
      are necessary before making any statements.

PMID- 15734093
TI  - Detection of feeding artery improves the ultrasound diagnosis of endometrial
      polyps in asymptomatic patients.
AB  - OBJECTIVE: To investigate whether transvaginal power Doppler imaging of the
      vascularity improves the ultrasound detection rate of endometrial polyps in
      symptomatic and asymptomatic patients. STUDY DESIGN: Forty-one patients with
      endometrial polyps confirmed by operative hysteroscopy and histologic
      examination. They were all examined with grey-scale and subsequent power Doppler
      enhanced ultrasound preoperatively according to the same protocol. Double layer
      endometrium and detailed endometrial morphology were described at grey scale
      scan. With power Doppler imaging pattern of endometrial vascularity. In the
      presence of a single feeding artery the ultrasound diagnosis of an endometrial
      polyp was made. RESULTS: With grey-scale imaging 20 polyps (49%) were recognized,
      while the subsequent application of power Doppler diagnosed the remaining 21
      polyps increasing the overall detection rate to 10% (P < 0.01). The grey-scale
      detection rate for the polyp was 11/30 (0.37) in the asymptomatic patients and
      9/11 (82%) in the symptomatic patients. No difference in endometrial thickness
      was observed. With power Doppler imaging, the detection rate for the feeding
      arteries was 97% (29/30) in the asymptomatic polyps and a similar 91% (10/11) in
      the symptomatic polyps. In the 21 polyps, where imaging of the vascularity was
      the only diagnostic marker, all but two were asymptomatic. CONCLUSION: Power
      Doppler enhanced ultrasound detection of the feeding vessels can be a simple, non
      invasive and highly effective first line test for the diagnosis of endometrial
      polyps in asymptomatic patients.

PMID- 15734094
TI  - Significance of the O6-methylguanine-DNA methyltransferase and glutathione S
      transferase activity in the sera of patients with malignant and benign ovarian
      tumors.
AB  - OBJECTIVE: To demonstrate O6-methylguanine-DNA methyltransferase (MGMT) and
      glutathione S-transferase (GST) activities by analyzing the sera separately
      obtained from patients with malignant ovarian tumors, benign ovarian tumors, and
      healthy individuals. STUDY DESIGN: Fourty-nine patients with ovarian cancer, nine
      patients with benign tumors, and 22 healthy women were included in this study.
      Blood samples were obtained from all the subjects in the malignant-tumor, benign
      tumor, and control groups. Patients with malignant tumors underwent second and
      third phlebotomies one week following the surgery and after the chemotherapy
      regimen, respectively. MGMT, GST, and protein levels were measured for each serum
      sample. GST activity of the samples was measured by the method of Habig et al.
      using l-chloro-2-4 dinitrobenzene (CDNB) as substrate. MGMT activity was measured
      by the transfer of radio labelled methyl groups from a prepared MG-DNA substrate
      to the enzyme fraction of serum. Protein concentration was measured by biuret
      method. RESULTS: Our work demonstrated that untreated patients with malignant
      ovarian tumors revealed significantly greater MGMT and GST activities in their
      sera than did both healthy individuals and patients with benign ovarian tumors,
      while no significant difference was found between the healthy group and the
      patients with benign ovarian tumors with respect to their sera MGMT and GST
      activities. GST activity following chemotherapy was significantly lower than the
      postoperative values preceding chemotherapy. A relationship between sera MGMT and
      GST activities, tumor histology and pathology was not found in this study.
      CONCLUSION: Our work suggests the fact that detection of sera MGMT and GST
      activities is important in diagnostic and therapeutic approaches during the
      course of ovarian cancer.

PMID- 15734096
TI  - Apoptosis of HeLa cell lines incubated with retinol.
AB  - PURPOSE: The aim of the study was to evaluate a soluble form of APO-1/Fas antigen
      in supernatants from HeLa cell line culture after 24 and 72 h of incubation with
      selected retinoic acid concentrations. MATERIALS AND METHODS: HPV18-positive cell
      lines were cultivated with All-trans-retinoic acid (ATRA) at concentrations of 1
      x 10(-6) and 1 x 10(-9) M. The cultures were incubated for 24 and 72 h. A control
      culture with 3 microl of DMSO was incubated under identical conditions. The
      concentrations of soluble APO-1/Fas antigen in cell culture supernatants were
      estimated using an ELISA method. RESULTS: The culture with 72-h incubation with
      retinoic acid proved to be toxic to cells and was excluded from the analysis. The
      results obtained showed a significantly lower concentrations of soluble APO-1/Fas
      antigen in supernatants from cell lines incubated with retinol for 24 h than in
      the controls. CONCLUSIONS: The higher concentrations of soluble APO-1/Fas antigen
      in supernatants from the HeLa cell line without retinol may constitute a
      protective mechanism of the cells infected with the virus before undergoing
      Fas/FasL-dependent apoptosis. Lower concentrations of sAPO-1/Fas antigen in the
      supernatant from HeLa cell culture incubated with retinol may suggest that
      mechanisms protecting infected cells against Fas/FasL-mediated apoptosis become
      defective under the influence of retinol. Our studies confirm that Vitamin A and
      its analogues inhibit the proliferation of cells associated with HPV infection
      and suggest promising effects of retinoid therapy in inhibiting the progression
      of early cervical lesions to cancer.

PMID- 15734095
TI  - Endometrial resection and preoperative LH-RH agonists: a prospective 5-year
      trial.
AB  - OBJECTIVE: To evaluate the benefits of systematic preoperative treatment with LH
      RH agonists prior to endometrial resection (ER). STUDY DESIGN: The study
      population was made up of 98 premenopausal women who underwent resectoscopic
      treatment for abnormal uterine bleeding (AUB) between January 1996 and December
      1997. Only patients with endometrial polyps or dysfunctional bleeding were
      included. The population was divided into two groups: patients who had (group B)
      and those who had not (group A) received LH-RH before the surgical intervention.
      RESULTS: ER was carried out as a single procedure in 66 (67.5%) of the patients.
      ER plus polypectomy was necessary in 32 (32.5%) patients. There were no
      differences between the two groups as far as the operating time and total volume
      of distension medium were concerned. No intraoperative complications were seen in
      either group. A higher negative balance of distension medium was achieved in
      group A (320 +/- 23 mL versus 187 +/- 16 mL; P < 0.001), and this difference was
      not modified when cases with polyps were excluded. The failure rate was similar
      in both groups both at 12 months [group A 6 (14.8%) versus group B 7 (14.9%)
      patients] and at 60 months [group A, 11 (21.6%) versus group B 10 (21.2%)
      patients]. Likewise, the amenorrhea and hypomenorrhea rates at 12 months and at
      60 months were also shown to be the same in both groups. When two doses of LH-RH
      are used and the failure rate is taken into account the cost of an acceptable
      outcome increases from 843.37 Euro to 1373.49 Euro per patient, while the total
      cost of a hysterectomy is 1355.42 Euro. CONCLUSIONS: Endometrial suppression with
      LH-RH agonists did not guarantee better results of ER, but they are strongly
      recommended during the learning curve to achieve a safer procedure.

PMID- 15734097
TI  - Why do women still develop cancer of the cervix despite the existence of a
      national screening programme?
AB  - The study looked at why women developed invasive cervical cancer during a 10-year
      period. It reviewed the hospital records of 66 patients with cervical cancer with
      an age range of 21-81 years. Screening non-attenders accounted for a
      disproportionate number of cases. The proportion of women who had never been
      screened did not vary during the study period. Attention needs to focus on
      reasons why these women do not attend.

PMID- 15734098
TI  - Mature cystic teratoma with intracystic fat balls in a postmenopausal woman.

PMID- 15734099
TI  - An incidental zygomycetes-like placental infection.

PMID- 15734100
TI  - A study to determine the use of medicines and drugs of abuse in high-risk early
      pregnancy.

PMID- 15734101
TI  - Monochorial monoamniotic twin pregnancies: targeted surveillance reduces the
      risks of cord entanglement.

PMID- 15734102
TI  - Weil's syndrome in pregnancy.

PMID- 15734104
TI  - Isolation of Delta9-THCA-A from hemp and analytical aspects concerning the
      determination of Delta9-THC in cannabis products.
AB  - A simple procedure based on a common silica gel column chromatography for the
      isolation of Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) from hemp in a
      multi-milligram scale is presented. Further, the decarboxylation reaction of
      Delta9-THCA-A to the toxicologically active Delta9-tetrahydrocannabinol (Delta9
      THC) at different analytical and under-smoking conditions is investigated.
      Maximal conversion in an optimised analytical equipment yields about 70% Delta9
      THC. In the simulation of the smoking process, only about 30 % of the spiked
      substance could be recovered as Delta9-THC.

PMID- 15734105
TI  - Virtopsy: postmortem imaging of the human heart in situ using MSCT and MRI.
AB  - The rapid further development of computed tomography (CT) and magnetic resonance
      imaging (MRI) induced the idea to use these techniques for postmortem
      documentation of forensic findings. Until now, only a few institutes of forensic
      medicine have acquired experience in postmortem cross-sectional imaging.
      Protocols, image interpretation and visualization have to be adapted to the
      postmortem conditions. Especially, postmortem alterations, such as putrefaction
      and livores, different temperature of the corpse and the loss of the circulation
      are a challenge for the imaging process and interpretation. Advantages of
      postmortem imaging are the higher exposure and resolution available in CT when
      there is no concern for biologic effects of ionizing radiation, and the lack of
      cardiac motion artifacts during scanning. CT and MRI may become useful tools for
      postmortem documentation in forensic medicine. In Bern, 80 human corpses
      underwent postmortem imaging by CT and MRI prior to traditional autopsy until the
      month of August 2003. Here, we describe the imaging appearance of postmortem
      alterations--internal livores, putrefaction, postmortem clotting--and distinguish
      them from the forensic findings of the heart, such as calcification,
      endocarditis, myocardial infarction, myocardial scarring, injury and other
      morphological alterations.

PMID- 15734106
TI  - Pathology of peliosis.
AB  - Peliosis is a pathological entity characterized by the gross appearance of
      multiple cyst-like, blood-filled cavities within parenchymatous organs. Peliosis
      has been related to several underlying debilitating illnesses such as
      tuberculosis, hematological malignancies, the acquired immunodeficiency syndrome
      (AIDS), and post-transplant immunodeficiency, as well as intravenous drug abuse,
      chronic alcoholism, and in conjunction with the intake of oral contraceptives or
      steroids. The classical pathoanatomical concept is based upon the opinion that
      peliosis exclusively develops in organs belonging to the mononuclear phagocytic
      system (liver, spleen, bone marrow, and lymph nodes). However, a paucity of
      studies indicates that other organs such as lungs, parathyroid glands, and
      kidneys may be affected too. Concerning the underlying pathogenetic mechanisms of
      onset and maintenance of peliosis, the morphological data obtained by different
      investigators suggest that there is more than one path of formal pathogenesis
      (e.g., congenital malformation of vessels manifesting under altered local
      intravascular pressure conditions, acquired vascular disorder triggered by toxic
      noxae, active proliferation of vessels corresponding to the benign end on the
      spectrum of neoplastic vascular lesions). In the liver, at gross inspection, the
      peliotic lesions give the cut sections a "swiss cheese" appearance.
      Microscopically, two different types of peliosis can be distinguished in the
      liver: (1) "parenchymal peliosis" consisting of irregular cavities that are
      neither lined by sinusoidal cells nor by fibrous tissue, and (2) "phlebectatic
      peliosis" characterized by regular, spherical cavities lined by endothelium
      and/or fibrosis. One of the differential diagnoses that most closely resembles
      peliosis hepatis is secondary hepatic congestion due to veno-occlusive disease or
      the Budd-Chiari syndrome. In the spleen, the peliotic lesions may be arranged
      sporadically, disseminated, or in clusters in an uneven distribution pattern.
      Histologically, the cavities show frequently well-demarcated margins that may
      appear focally lined by sinusoidal endothelium, or totally lack a clear cell
      lining. Differential diagnoses are hemangiomas and involvement of the spleen in
      hairy-cell leukaemia. Since the disease may culminate in spontaneous rupture of
      the affected organ and thus may mimic a violent death at autopsy, peliosis is far
      more than just another morphological curiosity. Awareness of peliosis at autopsy
      as well as an appreciation for the histopathological changes in less
      characteristic or advanced cases may become an important issue for both the
      forensic and clinical pathologist.

PMID- 15734107
TI  - Fatal pulmonary cement embolism following percutaneous vertebroplasty (PVP).
AB  - A case of fatal pulmonary embolism with acrylic cement occuring during a
      percutaneous vertebroplasty on account of a fracture of L1 is described. Autopsy
      confirmed the presence of large amounts of surgical cement in the paravertebral
      venous system and in the pulmonary arteries. This rare complication occurred
      because perivertebral venous cement migration was not recognized during
      vertebroplasty. To our knowledge, this is the first case of fatal pulmonary
      embolism caused by surgical cement following a percutaneous vertebroplasty.

PMID- 15734108
TI  - An unusual occupational accident: fall into a sewage plant tank with lethal
      outcome.
AB  - Occupational accidents, often presenting with lethal outcomes, are a rarely
      reported issue in forensic literature. However, these incidents are part of
      medicolegal casework with special regard to reconstruction, liabilities and
      insurance law-related issues, respectively. We report on a lethal occupational
      accident in a metropolitan sewage plant. When performing routine controls, a
      technician fell into an overflow sewer and was immediately pulled into a 30 cm
      diameter drain. Rescue efforts were initiated immediately, but had to be
      terminated due to gas warning. Rescue teams continued the search, however, the
      body remained undiscoverable. Forty-eight hours later, the cadaver was found in
      an adjacent digester tank, from where it was finally rescued. It was concluded,
      that the body had been transported between the overflow sewer and the digester
      tank through a 120 m pipeline with several 90 degrees bendings and branch
      connections with a minimum diameter of 25 cm at the discharge valve. On
      medicolegal examination, the cadaver showed marked signs of advanced
      decomposition caused by anaerobic microorganisms in the 37 degrees C biomass
      environment. Moreover, as a consequence of the passage of the pipeline system,
      signs of massive trauma (several comminuted and compound fractures) were
      disclosed at autopsy. To us, this is the first report on a lethal occupational
      accident in a sewage plant; our observations demonstrate the rapid progress of
      putrefaction in a warm anaerobic bacterial environment and the massive trauma
      sustained.

PMID- 15734109
TI  - A coronary artery crossed embolism of bone-marrow origin: proof of connections
      between pulmonary arteries and veins.
AB  - The paper describes a case of exceptionally rare crossed embolism of the coronary
      artery. The embolus material originated in bone-marrow released from rib
      fractures which occurred during resuscitation attempts. Autopsy did not reveal
      any anatomical abnormalities of the circulatory system, nor any disease-related
      changes, which could explain the occurrence of this embolism type, and therefore
      the only possible explanation is the presence of direct connections between
      pulmonary arteries and veins. The confirmation of this theory is the bone-marrow
      embolism of the pulmonary vein detected in the second case.

PMID- 15734110
TI  - Three cases of suspected hyperthermia with remarkable elevation of serum mast
      cell tryptase.
AB  - Tryptase is a neutral protease of human mast cells, and an important indicator of
      mast cell activation and degranulation in anaphylactic events. The elevation of
      serum mast cell tryptase (SMCT) is used for postmortem diagnosis of anaphylaxis.
      We have quantified the SMCT levels of 122 forensic autopsy cases with various
      causes of death and found only three where the SMCT levels were remarkably
      elevated, with values of 179, 68.9 and 69.4 ng/ml (normal level <13.5 ng/ml). The
      three cases were suspected to have suffered from hyperthermia, and the deaths did
      not seem to be related to causes of death where SMCT levels have been reported to
      be elevated in some cases. Two cases were patients who had been prescribed long
      term neuroleptics or antidepressants, and myoglobin was detected
      immunohistochemically in the renal tubules of both cases. The other case died of
      heatstroke. A possible mechanism of hyperthermia in SMCT elevation is discussed.

PMID- 15734111
TI  - Estimation of postmortem interval in real cases based on experimentally obtained
      entomological evidence.
AB  - Using the entomological evidence obtained in several forensic cases analyzed in
      our laboratory for comparison, we evaluated the results of an experimental study
      carried out in a semiurban setting to determine the structure of the
      sarcosaprophagous fauna from a Mediterranean region of SE Spain. In all, 18
      orders of arthropods were collected. The summarized experimental results refer to
      the most important taxa for estimating the postmortem interval. Thus, the
      seasonal character of certain Diptera species, such as Phaenicia sericata,
      Calliphora vicina, Chrysomya albiceps and Musca domestica, is cited. Among the
      Coleoptera, the role of Dermestidae as a necrophagous species, and of
      Staphylinidae and Histeridae as necrophilous, or Cleridae, Tenebrionidae and
      Nitidulidae as omnivorous, as well as their appearance on the corpse, is
      described. Among the Hymenoptera, Formicidae were as the most abundant group,
      acting as omnivores and not apparently related to any particular decomposition
      stage. The real cases are discussed using data from the literature and the
      experimentally obtained results. In every case, the most relevant factors for
      estimating PMI are briefly discussed, mentioning, when possible, the relation
      with the experimental results. We confirm the significance of the experimental
      results because they seem to be applicable to actual forensic cases, the details
      of which enlarge our very little knowledge on the subject in the Iberian
      Peninsula. The importance of regional faunistic studies of the sarcosaprophagous
      arthropod community, the results of which may be applied to forensic practice, is
      mentioned.

PMID- 15734112
TI  - Death due to positional asphyxia under severe alcoholisation: pathophysiologic
      and forensic considerations.
AB  - In contrary to "physical restraint", describing a fixed body position due to
      external devices, "positional restraint" is defined as an abnormal body position,
      resulting from accidental fixation under unfortunate circumstances. We report on
      a remarkable case of positional asphyxia of an alcoholised young man after a fall
      down a staircase. On external examination, the body showed petechiae of the
      conjunctivae and oral mucosa, abrasions on the left zygomatic region and scratch
      marks, respectively. Neither broken fingernails, etc. nor signs of external
      violence against the neck were found. Autopsy revealed haemorrhages in the
      praevertebral cervical musculature and Simon's sign. Haemorrhagic pulmonary edema
      and cerebral edema were observed; blood alcohol concentration: 2.60 g/l, urine
      alcohol concentration: 3.26 g/l. As cause of death, positional asphyxia after
      blunt head trauma has to be considered as well as lethal ethanol intoxication. To
      us, alcoholisation attributed to the fall and together with unconsciousness
      following blunt head trauma circumvented self-rescue efforts, and therefore,
      aggravated the potentially lethal impact of positional restraint.

PMID- 15734113
TI  - Contact shot with unusual soot pattern.
AB  - In a suicidal shot to the temple two roundish zones of powder soot blackening
      were found above the entrance wound. The paired zones of powder soot blackening
      were caused by two gas outlets located on the upper side of the muzzle end of the
      weapon used (converted blank cartridge pistol of make Rhoner). The conclusions
      that can be drawn from this particular soot pattern with regard to the type of
      the weapon, the muzzle-to-target distance, the direction of fire and the way of
      holding the weapon are discussed.

PMID- 15734114
TI  - STR data for the Amp FlSTR Profiler Plus loci among 27 populations of different
      social hierarchy from southern part of Andhra Pradesh, India.
AB  - Allele frequency for the 9 STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51,
      D5S818, D13S317, D7S820) were estimated from a total of 1096 individuals
      belonging to 27 endogamous populations from the state of Andhra Pradesh, India,
      covering the entire gamut of socio-economic variation of the linguistic region.
      These loci are found to be highly polymorphic within the populations with high
      levels of average heterozygosity (>0.80). However, the allele frequency
      distributions are fairly uniform across the populations in case of these loci
      suggesting relatively greater homogeneity among the populations. Regrouping
      populations into five broad socio-economic categories further reiterated the
      homogenous pattern of genetic diversity.

PMID- 15734115
TI  - Y-chromosome STR haplotype diversity in Brazilian populations.
AB  - A sample of 198 unrelated males distributed among the five geopolitical regions
      in Brazil were typed for the minimal Y-STR haplotype composed of microsatellite
      loci DYS19, DYS385I/II, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393.
      Gene frequency data, gene diversity, haplotype diversity and power of
      discrimination were estimated. An AMOVA indicated that 99.97% of the haplotypic
      variation is found within regions and only a small 0.03% and non significant
      variation is found among the five regions (Fst=0.00031, P-value=0.43). This
      result suggests that a single national database of Y-STR haplotypes can be used
      in the quantitative assessment of matches in forensic casework in the Brazilian
      population. A significant haplotype diversity of 99.8% was found and 172
      different haplotypes were observed in 198 chromosomes. Haplotype (14-11, 14-13-29
      24-11-13-13) with five occurrences in 198 chromosomes was the most frequent in
      Brazil.

PMID- 15734116
TI  - Genetic variability of 16 Y-chromosome STRs in a sample from Equatorial Guinea
      (Central Africa).
AB  - Nine Y-STR loci from the "minimal haplotype" included in Y-STR Haplotype
      Reference Databases (YHRD) together with eight additional Y-STRs (DYS437, DYS438,
      DYS439, DYS460, DYS461, GATA C4, GATA H4 and GATA A10) were analyzed in a sample
      of 101 males from Equatorial Guinea living in Madrid. Haplotype and allelic
      frequencies were calculated and genetic diversities were estimated for each
      genetic system as well as for the whole haplotype. An unexpected high frequency
      (6%) of intermediate alleles (13.2 and 14.2) was found in DYS385. For DYS19, two
      alleles were found in one sample. Another sample failed to amplify with DYS393
      primers using either PowerPlex Y System (Promega Corporation) or the Y-PLEXtrade
      mark 12 (Reliagene, New Orleans, LA) commercial kits. Comparison between
      Equatorial Guinea and another African population (Mozambique; South East Coast)
      revealed a significant pairwise Phi(st) value between them (Phi(st)=0.03309;
      P=0.00000).

PMID- 15734117
TI  - [Bereavement after a sudden infant death: place of a psychological support].

PMID- 15734118
TI  - [Oral morphine administration for children's traumatic pain].
AB  - OBJECTIVES: To study the compliance of prescription, the efficacity and the
      adverse events of oral morphine used in the pediatric emergency department (ED)
      in traumatic pains. METHOD: This prospective study was conducted in the ED from
      october 2002 to september 2003. Children aged six months to 16 years with a
      visual analogic scale (VAS) score higher than 70 or with a traumatic member
      deformation received oral morphine (0,5 mg/kg). Pain was assessed every 30
      minutes using two scales: behavioral observation by the faces scale and objective
      pain scale (OPS) for children less than five years, behavioral observation by the
      faces scale and self-report by VAS for children older than five years. The
      compliance of prescription, the pain scores and the adverse events were studied.
      RESULTS: Ninety-one children received oral morphine and seventy-four children
      were studied. Seventy per cent of prescriptions were in accordance with the
      recommendations. For patients younger than five years a rapid decrease of pain
      was observed in thirty minutes. The pain's reduction was respectively 79 and 84%
      with faces scale and OPS when they left ED. For children older than five years,
      pain's reduction was more important and more rapid when pain assessment was made
      by nurses than when it was self-reported in the first hour (pain reduction 58,2
      and 36,1%). When leaving, pain reduction was the same with the two different
      assessments. No major adverse event was noted. CONCLUSION: Use of oral morphine
      in ED is simple, with a few numbers of adverse events. None was severe.
      Efficiency is correct after 30 to 60 minutes.

PMID- 15734119
TI  - [DiGeorge syndrome, a review of 52 patients].
AB  - The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or
      velo-cardiofacial syndrome. The phenotypic variability was noted in the "CATCH
      22" acronym. This acronym doesn't recapitulate the full spectrum of the symptoms.
      The diagnosis of this syndrome can be done with the prenatal diagnosis, with
      fetal pathology or with a child alive. METHODS: Review of 52 cases with the
      microdeletion 22q11. Six cases were diagnosed during the prenatal period, 12
      cases at fetal pathology examination, and 34 cases during infancy. RESULTS:
      Cardiac malformations were the major indications (75%) to search for the
      microdeletion. The facial dysmorphy was difficult to diagnose during the
      antenatal period or in dead foetus, thereby it was not often recognized. The
      renal anomalies usually present in 35% of cases, were diagnosed in only 6 to 16%
      of the cases in our study. CONCLUSION: Phenotypic diversity of the DiGeorge
      syndrome is important. Its knowledge allows to better determine the indications
      of the research of the microdeletion. 22q11.2.

PMID- 15734120
TI  - [Congenital hyperinsulinism of infancy: surgical treatment in 60 cases of focal
      form].
AB  - Congenital hyperinsulinism of infancy is a severe disease that leads to important
      brain damage. Two different forms of the disease have been identified by
      pathologists: a diffuse and a focal form. A specific genetic anomaly identified
      in focal forms has never been described in diffuse ones. However, for most of
      authors, failure of medical treatment results in near-total pancreatectomy in all
      cases, which ends in diabetus. The aim of this retrospective study was to assess
      the results of elective partial pancreatectomy performed in 60 cases of focal
      form of hyperinsulinism over the last 18 years. Fifty-eight patients were cured
      with euglycemia at both fasting and hyperglycaemic tests without insulin
      dependent diabetes mellitus. One patient is still in hypoglycaemia from
      unrecognized lesion; insulin-dependent diabetes mellitus occurred in one case
      nine years after surgery (a near-total pancreatectomy has been performed because
      of unknown focal form, in 1985).

PMID- 15734121
TI  - ["Audio 4": a simple and quick speech audiometry test for moderate hearing loss
      screening in four-year-old children].
AB  - The need for repeated auditory screening throughout early childhood faces the
      obstacle of the lack of objective validated material. OBJECTIVES: The goal of
      this two-year prospective study was to create and validate frequency-based
      word/picture lists appropriate for four-year-olds. Words were chosen not on the
      basis of the acoustic frequency of phoneme production, but on frequencies
      corresponding to their optimal recognition. Responses thus were to predict pure
      tone threshold curves. MATERIAL AND METHODS: First of all, the linguistics
      laboratory created lists. Next, we proceeded to validate the form of the test:
      this involved verifying that the words selected on the basis of their frequency
      characteristics were common and well-known to children of this age. During the
      first year of the study, the picture boards were tested in a hospital
      otolaryngology service (66 children) and in a public health service (500
      children) and corrected. RESULTS: All of the words and pictures were known during
      the next year by 5088 children. The second step was the audiometric validation of
      the test in a paediatric otolaryngology service. We compared classification of
      normal and impaired ears according to tonal audiograms and according to "Audio
      4": 360 children were tested. Results were the following ones: Se: 0.81, Sp:
      0.96, PPV: 0.91, NPV: 0.93. "Audio 4" therefore allows for prediction of pure
      tone curves. CONCLUSION: This gives us hope that, directly interpretable by
      physicians, Audio 4, a rapid test which is attractive to children, will be used
      in diagnostic paediatric examinations whenever necessary.

PMID- 15734122
TI  - [Kidney transplanted child and sport practices].
AB  - OBJECTIVE: Evaluation of physical capacity in kidney transplanted children for
      sport practice adequacy. POPULATION AND METHODS: A retrospective study was
      carried out in 32 children transplanted at least one year before evaluation. We
      studied auxology, respiratory function testing, cardiovascular parameters at rest
      and after exercise, and aerobic capacity performed during a triangular effort
      test. RESULTS: Kidney transplanted children were smaller and had a higher body
      mass index (IMC). Breathing parameters and cardiac ultrasound examinations were
      normal in all but one child. After exercise, four children had high systolic
      blood pressure requiring a treatment adaptation. Lower values of maximal aerobic
      power (Pmax) and oxygen maximal uptake (VO2max) were noticed, mainly in girls.
      CONCLUSION: Kidney transplanted children have a good physical exercise tolerance.
      Therefore they can be allowed to practise sports at school or in a club after a
      normal effort test (taking into account the risk of transplant trauma).

PMID- 15734123
TI  - [Retrobulbar optic nevritis and chicken pox: a case report in a child].
AB  - We report here the case of a three-year-old boy presenting with an optic neuritis
      during the invasive phase of a chicken pox. This clinical, infrequent picture,
      can be directly due to the virus or be secondary to an auto-immune mechanism. The
      examination of the ocular fundus, the profile of the spinal fluid, the MRI and
      the measure of visual evoked potential allow to reach diagnosis and to identify
      the type of lesion. There is no consensus on the treatment of this optic neuritis
      and the current attitude is therapeutic abstention because of a rapid spontaneous
      improvement. Cerebellitis, meningitis can also be seen during chicken pox. Their
      evolution is quickly favorable, not requiring additional exam. Encephalitis can
      result from an auto-immune lesion of the white matter and require then the use of
      corticoids with antiviral drugs.

PMID- 15734124
TI  - [Parvovirus B19 thrombocytopenic purpura complicated with a cerebral hemorrhage].
AB  - Severe hemorrhage complications are rare in idiopathic thrombocytopenic purpura.
      This pathology is often considered as benign. CASE REPORT: We report the case of
      a four-year-old boy presenting a parvovirus B19 idiopathic thrombocytopenic
      purpura. Despite early and repeated use of intravenous immunoglobulin, the
      evolution was characterized by the secondary apparition of a cerebral hemorrhage.
      It was lethal seven days after the initial diagnosis. CONCLUSION: Parvovirus B19
      should be investigated as an etiologic agent of idiopathic thrombocytopenic
      purpura, using PCR. The unpredictive aspect of severe hemorrhage complications,
      especially cerebral hemorrhages, explains the potential severity of this disease.

PMID- 15734125
TI  - [Dental fluorosis: etiological diagnosis].
AB  - Dental fluorosis is defined by an alteration of dental hard tissues and occurs
      when fluoride intakes are excessive. Medical authorities recommend a total daily
      consumption of 0.05 mg/kg of fluoride, without exceeding 1 mg. OBSERVATIONS: The
      two reported clinical observations confirm that fluorosis is a consequence of
      excessive fluoride intakes. Etiological diagnosis allows a better understanding
      of this pathology. In the majority of the cases, dental fluorosis can be avoided.
      CONCLUSION: Dental fluorosis is the sole risk of fluoride use, but it is not a
      fate. It does not constitute a problem of public health in France and the
      benefits/risks ratio is widely in favour of the use of fluoride.

PMID- 15734126
TI  - [Acute abdominal pain in a 8-year-old girl with Epstein-Barr infection].
AB  - Abdominal pain is uncommon in patient with Epstein-Barr infection and is usually
      attributed to an enlargement of the liver or spleen. We report on an 8-year-old
      girl with a pseudoperitonitis due to a mesenteric lymphadenitis associated with
      Epstein-Barr infection. Outcome was favourable without surgery. We review the
      different causes of abdominal pain occurring during Epstein-Barr infection.

PMID- 15734127
TI  - [Clinical aspects and outcome of meningococcal disease due to Neisseria
      meningitidis of serogroup W135 in 5 children].
AB  - Meningococcal disease due to Neisseria meningitidis of serogroup W135 (N.
      meningitidis W135) is increasing in France. Clinical and outcome data concerning
      these infections in children are scarce. We report five cases of children
      hospitalized between June 2000 and December 2002 for N. meningitidis W135
      infection. Extra-meningeal septic and/or non-septic complications were frequent
      and a prolonged post meningococcal inflammatory syndrome was reported. In N.
      meningitidis W135 infections a careful clinical evaluation of potential extra
      meningeal complications and a long term follow up of children are needed.

PMID- 15734129
TI  - [Cord blood banking: public versus private banks--facts to ponder and consider].
AB  - Since 1988, allogeneic cord blood transplantations have been used in the
      hematology and oncology area. Cord blood banks, either public or from non-profit
      corporations, opened in several countries. They organized themselves into a world
      wide network permitting broad and quick graft availability all over the world.
      Cryopreservation modalities and biological safety were strongly defined according
      to laboratory good practices. More recently, in the United States, Canada and
      some European and Asian countries, commercial companies created for-profit cord
      blood banks. They offer families the possibility of privately storing the cord
      blood of their children. Then, if a child gets sick and needs a hematopoietic
      stem cell transplantation, it is possible to use the cord blood for an autograft.
      These companies present this service, relatively expensive for the families, as a
      true biological insurance. Also, they capitalize on families' hopes that
      scientific progress will increase cord blood autografts and other stem cell
      medical applications. In this work, we review available scientific data, ethical
      considerations and laws that can contribute to an informed reflection.

PMID- 15734128
TI  - [Erythema nodosum and adenopathy in a 15-year-old boy: uncommon signs of cat
      scratch disease].
AB  - Erythema nodosum rarely occurs in childhood and can be caused by cat scratch
      disease, as a result of agent Bartonella henselae. We report the case of a
      teenager who presented erythema nodosum and bilateral inguinal adenitis. Cat
      scratch disease diagnosis was confirmed by anti-Bartonella henselae serologies.
      Despite an appropriate antibiotic therapy, evolution was unfavourable with
      adenitis abcedation requiring surgical drainage. CONCLUSION: Erythema nodosum in
      children must let think to cat scratch disease among others etiologies.

PMID- 15734130
TI  - [Immunity and immunosuppression in childhood idiopathic nephrotic syndrome].
AB  - Steroid sensitive idiopathic nephrotic syndrome is a T-cell disorder
      characterized by a functional renal impairment. Concluding a still relevant
      demonstration involving cellular immunity in the pathogenesis of the disease, R.
      Shalhoub in 1974 suggested a "special role for the thymus" based on the
      efficiency of steroids and alkylating agents, dramatic recoveries following
      measles, sensibility to bacterial infection due to a lack of cooperation between
      T and B cell and association to Hodgkin disease. As a matter of fact, the
      selected drugs based on medical empirism somehow enhance thymocytes apoptosis and
      negative selection of T cell, except cyclosporin. Steroids have been the first
      historical treatment of idiopathic nephrotic syndrome and have steadily been the
      first-line treatment for 50 years. Their unavoidable ability to induce rapid
      recovery of proteinuria and long-lasting or definite remission are dependent to a
      strict compliance to treatment. Indications of steroids-sparing treatments are
      not that clearcut in patients with steroids intoxication. Objectively, efficiency
      of levamisole and cyclophosphamide are much more limited than previously reported
      and cyclosporin nephrotoxicity might severely impair renal function following
      long-lasting treatment as well as it may paradoxically increase the activity of
      the disease. An alternate strategy to those currently adopted would use
      cyclosporin as the first-line steroids-sparing treatment during a very limited
      period, awaiting favourable ageing of patients and natural dampening activity of
      the disease to a full efficiency of alkylating agents. Compared to
      cyclophosphamide and cyclosporin, the relative safety of levamisole is
      encouraging to a more frequent uses. Its association to a full dose of prednisone
      in the treatment of the inaugural episode should be investigated. According to
      the limitations of those therapies, emerging drugs as mycophenolate might be
      worthwhile in the treatment of nephrotic patients.

PMID- 15734131
TI  - [Pharmacologic treatment of acute migraine attack in children].
AB  - Migraine, according to the criteria of the International Headache Society, occurs
      in about 5 to 10% of children. Management of acute headache is only one of the
      parts of the treatment, along with identification of migraine precipitants,
      adjustments in lifestyle, and when necessary the use of preventive therapy, which
      can include non pharmacologic (relaxation or biofeedback) or pharmacologic
      treatment. In the acute migraine attack, a single dose of either ibuprofen 10
      mg/kg or paracetamol 15 mg/kg has been shown to be effective, with only a few
      adverse effects. In severe migraine attacks, dihydroergotamine mesylate
      administered orally (20 to 40 microg/kg) or intravenously (maximum 1 mg/day) may
      be helpful, but there have been no large placebo-controlled trials of this
      treatment. Among the different triptans, it is the sumatriptan nasal spray whose
      efficacy has been best demonstrated. The most frequent adverse event is
      transitory unpleasant taste.

PMID- 15734132
TI  - [Epidemiology of meningococcal infections in children in Loire-Atlantique and
      neighbouring areas from 1997 to 2002].

PMID- 15734133
TI  - [National planning for perinatology 2005-2007: breast feeding is neglected!].

PMID- 15734134
TI  - [Evaluation of direct costs of child severe malaria management at the general
      hospital of Bonoua, Cote-d'Ivoire].

PMID- 15734135
TI  - [Allergic rhinitis in childhood].
AB  - Prevalence of allergic rhinitis has increased in the past years. The
      determination of the aeroallergens involved is important. Children with
      persistent rhinitis must be evaluated for asthma. Early treatment of allergic
      rhinitis may avoid asthma onset. The management of allergic rhinitis must include
      allergen avoidance, pharmacological treatment and immunotherapy. Sublingual
      swallow immunotherapy is a safe and effective method of treatment.

PMID- 15734137
TI  - [Sexual female mutilation].
AB  - Each year, two million young girls are at risk of female sexual mutilation.
      Pediatricians are likely to be confronted with this problem. They must know to
      identify it as well as the complications to ensure a concerned assumption of the
      families, in the respect of the law.

PMID- 15734136
TI  - [Imaging in paediatric epilepsy].
AB  - Epilepsy is a chronic disease, often with an onset during childhood and
      characterized by spontaneous and recurrent seizures. It concerns 0.5-1% of
      children under 16 years of age. A classification proposed by the International
      League Against Epilepsy (ILEA) in 2001 takes into account recent genetic factors
      involved in epilepsy and attenuates the sharp demarcation between generalized and
      partial seizures. This classification tends to define whether imaging is
      indicated or not. Imaging is useless in simple cases of fits associated with
      hyperthermia and in benign idiopathic epilepsy. It is debated if it is a first
      episode of epilepsy without a particular context and no neurological signs. In
      all other cases of epilepsy in children, imaging is indicated. In descending
      order of frequency the possible causes include malformations (as abnormal gyral
      development and phakomatoses), hypoxic-ischemic lesions, non-accidental injuries,
      infections, metabolic diseases and tumors. Being much more sensitive than
      computed tomography (CT), magnetic resonance imaging (MRI) is the technique of
      choice to identify an underlying cause in symptomatic epilepsy. Clinical data are
      mandatory in order to direct a proper MRI investigation. The recently developed
      diffusion-weighted sequence is particularly useful in the acute phase of certain
      events such as hypoxia-ischemia, trauma and metabolic disease. CT scan is used in
      emergency situations and also as a complement to MRI for example to identify
      calcified lesions. In this way, imaging contributes to establish the nature and
      define the extension of epileptogenic lesions, thereby guiding therapeutic
      management. MRI also allows follow-up of the consequences of repeated seizures
      (such as mesial temporal sclerosis and selective neuronal necrosis) on the
      cerebral parenchyma and plays a role in the establishment of a prognosis.

PMID- 15734139
TI  - [New developments in 2005 for the management of visual deficit in the infant].
AB  - The main progress in ophthalmopediatrics is the knowledge of the importance and
      efficacy of visual refraction defects screening. This screening has to be the
      earliest possible, allowing a glass equipment preventing complications:
      amblyopia, strabismus. This screening allows the same time screening of organic
      anomalies and early treatment.

PMID- 15734138
TI  - [Treatment of exacerbation of asthma: what are today's issues?].
AB  - During past decades, major progress has been accomplished in the management of
      acute asthma. Most recent recommendations include evidence-based rationale. The
      improved quality of clinical guidelines makes them efficient models for medical
      education. The pediatric pharmacopoeia provides a great variety of choices of
      drugs as well as for asthma medical devices. These innovations dramatically
      facilitated the medical management of asthmatic children, but they did not solve
      all problems. Physicians now use higher doses of salbutamol, but the early
      prescription of systemic glucocorticoids for moderate exacerbation of asthma is
      still underused, given the most recent clinical guidelines and meta-analysis.
      Furthermore, repeated emergency department visits to the wards and lack of
      primary care physician should systematically be appraised when evaluating
      severity, as they are both major risk factors for severe exacerbations, even
      though they are not considered in acute asthma severity scores. Finally,
      initiating (or reinforcing) patient education at the time of exacerbation also
      presents important challenges, as emergency visits are a favorable moment to
      commence the therapeutic education of the child and his family. Indeed, framing
      the controller medications and educating families about how to manage the disease
      and to improve their domestic environment are the genuine tools available for the
      prevention of asthma exacerbations, and particularly those most severe.

PMID- 15734140
TI  - [Children's strangulated inguinal hernia].
AB  - The inguinal hernia, malformations caused by persistence of peritonea-vaginal
      duct, is frequent in children. It is a benign affection as long as it is not
      strangled. During our five-year-retrospective study, we have found 32 cases (30
      boys and 2 girls) of strangled inguinal hernia. There are 78,12% of cases under
      five years old. In 54%, the hernia was on the right side. Malnutrition and
      inguinoscrotal hernia are very exposed to strangulation. We observed obstruction
      syndrome in 81,25% of cases. We have to deplore one case of scrotal fistulae by
      intestinal necrosis and two cases of testicle necrosis. For all of our patients,
      the peritonea-vaginal duct was closed with ligature, associated with pre
      funicular parietal refection. One case of recurrence is found in postoperative
      time.

PMID- 15734141
TI  - [Surgical treatment of tympanic perforation in children].

PMID- 15734142
TI  - A new lipase in regulating lipid mobilization: hormone-sensitive lipase is not
      alone.
AB  - Three papers recently appeared simultaneously that identify a new triacylglycerol
      lipase. Zimmerman et al. identified this lipase as adipocyte triacylglycerol
      lipase (ATGL). Jenkins et al. identified it as the zeta-isoform of a calcium
      independent phospholipase A(2) (iPLA(2)), whereas Villena et al. found this
      enzyme and called it desnutrin. Interestingly, if, as implied, this lipase works
      in concert with hormone-sensitive lipase, then our concept of regulated fatty
      acid mobilization from triacylglycerols will have to be revised.

PMID- 15734143
TI  - Andropause: invention, prevention, rejuvenation.
AB  - There is a growing interest, as well as a booming industry, in the use of
      testosterone therapy for middle-aged and older men. This interest has led to the
      definition of a new condition, termed 'andropause', meaning the putative somatic
      consequences of gradually falling blood testosterone concentrations during male
      aging. This trend risks replicating both the rejuvenation fads of a century ago
      and the recent experience in estrogen therapy for menopause that has been
      propelled for decades by advocacy substituting for reliable scientific evidence.
      The current status and prospects for androgen therapy in middle-aged and older
      men should be evaluated critically from the perspective of male reproductive
      health during aging. This review appraises current knowledge with a focus on the
      questionable basis for using androgen therapy to improve male reproductive health
      during aging.

PMID- 15734144
TI  - Transcription factor cross-talk: the estrogen receptor and NF-kappaB.
AB  - The NF-kappaB family of transcription factors regulates many genes that are
      essential primarily for the development, maintenance and function of the innate
      and adaptive immune systems. Thus, aberrant activity of the nuclear factor NF
      kappaB has a role in many pathological conditions with inflammatory and
      autoimmune components. Estrogen receptors (ERs) are transcription factors that
      mediate the biological responses to the sex hormone estrogen and are essential
      for reproduction and for functions of the cardiovascular, skeletal and nervous
      systems. Recent studies have demonstrated molecular cross-talk between these
      families of transcription factors in which the ER mediates inhibition of NF
      kappaB activity at several levels. Such cross-talk between these important
      regulators of the endocrine and immune systems might be exploited for the
      treatment of cancer and inflammatory and autoimmune diseases.

PMID- 15734145
TI  - Role of SOCS2 in growth hormone actions.
AB  - Growth hormone (GH) has numerous effects in the body and is most commonly known
      for its role in regulating metabolism and body growth. Because GH is involved in
      many aspects of cell function, its signaling is tightly controlled by several
      pathways at both the extracellular and intracellular level. Suppressor of
      cytokine signaling-2 (SOCS2) is one such intracellular regulator of GH signal
      transduction. Expression of SOCS2 is tightly regulated and alteration of its
      levels leads to marked abnormalities in metabolism and growth. Unexpectedly, GH
      and SOCS2 have been recently shown to regulate neural development, neural stem
      cell differentiation and neuronal growth -- functions that might have important
      therapeutic implications for both repairing nervous system injuries and treating
      neurological disease.

PMID- 15734146
TI  - The role of insulin receptor signaling in the brain.
AB  - The insulin receptor (IR) is expressed in various regions of the developing and
      adult brain, and its functions have become the focus of recent research. Insulin
      enters the central nervous system (CNS) through the blood-brain barrier by
      receptor-mediated transport to regulate food intake, sympathetic activity and
      peripheral insulin action through the inhibition of hepatic gluconeogenesis and
      reproductive endocrinology. On a molecular level, some of the effects of insulin
      converge with those of the leptin signaling machinery at the point of activation
      of phosphatidylinositol 3-kinase (PI3K), resulting in the regulation of ATP
      dependent potassium channels. Furthermore, insulin inhibits neuronal apoptosis
      via activation of protein kinase B in vitro, and it regulates phosphorylation of
      tau, metabolism of the amyloid precursor protein and clearance of beta-amyloid
      from the brain in vivo. These findings indicate that neuronal IR signaling has a
      direct role in the link between energy homeostasis, reproduction and the
      development of neurodegenerative diseases.

PMID- 15734147
TI  - New functional imaging modalities for chromaffin tumors, neuroblastomas and
      ganglioneuromas.
AB  - Nuclear medicine modalities use radiolabeled ligands that either follow metabolic
      pathways or act on cellular receptors. Thus, they permit functional imaging of
      physiological processes and help to localize sites such as tumors that harbor
      pathological events. The application of positron emission tomography (PET)
      ligands to the specific pathways of synthesis, metabolism and inactivation of
      catecholamines found in chromaffin tumors, neuroblastomas and ganglioneuromas can
      be used to provide a more thorough localization of these types of tumor. Recent
      advances have been made in functional imaging to localize pheochromocytomas,
      paragangliomas, neuroblastomas and ganglioneuromas, including approaches based on
      PET with [(18)F]fluorodopamine, [(18)F]fluorohydroxyphenylalanine,
      [(11)C]epinephrine or [(11)C]hydroxyephedrine. Such functional imaging can
      complement computed tomography or magnetic resonance imaging and other
      scintigraphic techniques to localize these tumors before surgical or medical
      therapeutic approaches are considered.

PMID- 15734148
TI  - Antagonists of activin signaling: mechanisms and potential biological
      applications.
AB  - Activins are members of the transforming growth factor-beta (TGF-beta)
      superfamily that control many physiological processes such as cell proliferation
      and differentiation, immune responses, wound repair and various endocrine
      activities. Activins elicit these diverse biological responses by signaling via
      type I and type II receptor serine kinases. Recent studies have revealed details
      of the roles of inhibin, betaglycan, follistatin and its related protein
      follistatin-related gene (FLRG), Cripto and BAMBI in antagonizing activin action,
      and exogenous antagonists against the activin type I (SB-431542 and SB-505124)
      and type II (activin-M108A) receptors have been developed. Understanding how
      activin signaling is controlled extracellularly is the first step in providing
      treatment for wound healing and for disorders such as cachexia and cancer, which
      result from a deregulated activin pathway.

PMID- 15734149
TI  - Determination of amosulalol in human plasma using solid-phase extraction combined
      with liquid chromatography and ultraviolet detection.
AB  - Amosulalol is an antihypertensive drug with selective postsynaptic alpha 1 and
      non-selective beta blocking effects. A simple solid-phase extraction and high
      performance liquid chromatographic (HPLC) method has been developed and validated
      for the quantitative determination of amosulalol in human plasma. A reversed
      phase C18 column was used for the separation of amosulalol and ethyl paraben
      (internal standard) with a mobile phase composed of 0.025 M phosphate buffer (pH
      6.0).acetonitrile (73:27, v/v) at a flow rate of 1.5 mL/min. The ultraviolet
      detector was operated at the 272 nm wavelength. Intra- and inter-day precision
      and accuracy were acceptable for all quality control samples including the lower
      limit of quantification of 30 ng/mL. Recovery of amosulalol from human plasma was
      >95.6%. Amosulalol was stable in human plasma under various storage conditions.
      This method was used successfully for a pharmacokinetic study in plasma after
      oral administration of a single 20 mg dose of amosulalol hydrochloride to 16
      healthy volunteers.

PMID- 15734150
TI  - Non-enzymatic hinge region fragmentation of antibodies in solution.
AB  - Liquid formulations of monoclonal antibodies (MAbs) typically undergo
      fragmentation near the papain cleavage site in the hinge region, resulting in Fab
      and Fab+Fc forms. The purpose of this study was to investigate whether this
      fragmentation is due to proteases. Four closely-related MAbs were exchanged into
      a pH 5.2 acetate buffer with NaCl and stored at -20 degrees C, 5 degrees C, 30
      degrees C, or 40 degrees C for 1 month. Fragmentation generated size-exclusion
      chromatography (SEC) peak fractions that were analyzed by electrospray mass
      spectrometry to identify the cleavage sites. The effects of protein inhibitors or
      host cell proteins on fragmentation were also studied. The extent of
      fragmentation was equivalent for all four antibodies, occurring in the heavy
      chain hinge region Ser-Cys-Asp-Lys-Thr-His-Thr sequence. The fragment due to
      cleavage of the Asp-Lys bond showed two forms that differ by 18 Da. A synthetic
      peptide with the hinge region sequence terminating with Asp did not show
      fragmentation or the loss of 18 Da after incubation. Protease inhibitors did not
      affect rates of cleavage or modify sites of fragmentation. Degradation was not
      affected by host cell protein content. Fragmentation appears to be a kinetic
      process that is not caused by low levels of host cell proteases.

PMID- 15734151
TI  - Purification and some properties of Cu,Zn superoxide dismutase from Radix
      lethospermi seed, kind of Chinese traditional medicine.
AB  - Copper-zinc superoxide dismutase (Cu,Zn SOD) has been extracted, purified and
      characterized from Radix lethospermi seed (RLS), a kind of Chinese traditional
      medicine. Before extraction, the lipid was removed by super critical fluid
      extraction (SCF). Partial protein fractionation in the crude extract was affected
      by using 50-75% (NH(4))(2)SO(2). Subsequently, superoxide dismutase was
      fractionated by column chromatographies on DEAE-52, Sephadex G-200 and DEAE-52
      again. Pure Cu,Zn SOD had a specific activity of 4843 U/mg protein and was
      purified 267.2-fold, with a yield of 23.55%. The purified enzyme has a molecular
      weight of about 30,500+/-100 and is composed of two non-covalently joined equal
      subunits. Purity was confirmed by Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE), HPLC and mass spectroscopy. Amino acid content has
      been investigated. The enzyme was found to remain stable in the pH range 6.0-9.0
      at 25 degrees C and up to 45 degrees C at pH 7.8 for a 30 min incubation period.
      RLS Cu,Zn SOD appeared to have significant thermal stability lower than other
      Cu,Zn SODs, as revealed by irreversible heat inactivation at 60 degrees C. The
      enzyme was not inhibited by DTT, NaN(3) and beta-mercaptoethanol, but was
      inhibited by cyanide and hydrogen peroxide. Finally, in the presence of 2 mM
      ethylendiamine tetra acetic acid (EDTA) and sodium dodecyl sulphate (SDS), the
      enzyme showed approximately 18 and 34% activity loss.

PMID- 15734153
TI  - Metal ion-selective membrane prepared by surface molecular imprinting.
AB  - Surface molecular imprinting was applied to the preparation of an ion-selective
      polymeric membrane for the first time. The use of acrylonitrile-butadiene rubber
      and a porous solid support in the polymer matrix resulted in improved flexibility
      and mechanical strength of the imprinted membrane. The asymmetric porous
      structure of the membrane was observed by scanning electron microscopy. The
      selectivity of the zinc(II)-imprinted membrane was evaluated by competitive
      adsorption and permeation studies. The imprinted membrane showed higher
      adsorption affinity and permeation selectivity towards the imprinted zinc ion
      than the non-imprinted counterpart. On the basis of the results obtained, the
      permeation mechanism of the metal ions was considered to be hopping of metal ions
      on the binding sites in the membranes.

PMID- 15734152
TI  - Quantitative analysis of chondroitin sulfate in raw materials, ophthalmic
      solutions, soft capsules and liquid preparations.
AB  - We performed the quantitative analysis of chondroitin sulfate (CS) obtained from
      raw materials and various pharmaceutical preparations. To quantify CS content in
      raw materials and in an ophthalmic solution, each test sample and the authentic
      CS were first digested by chondroitinase ABC. The CS disaccharides produced were
      analyzed by strong anion-exchange high-performance liquid chromatography (SAX
      HPLC) and CS content was quantified by calculating the total peak areas of the
      disaccharides derived from a CS calibration curve. In the case of soft capsules,
      CS was first extracted with hexane followed by phenol-chloroform to remove oil
      and protein ingredients. The extracted CS samples were depolymerized by
      chondroitinase ABC and CS content was determined. Quantitative analysis of the
      disaccharides derived from raw materials and an ophthalmic solution showed the CS
      contents (%) were 39.5+/-0.1 to 105.6+/-0.1 and 103.3+/-1.2, respectively. In
      case of CS analysis in soft capsules and liquid preparations, the overall
      recovery (%) of the spiked CS was 96.79+/-0.53-103.54+/-1.78 and 97.10+/-1.82 to
      103.17+/-2.34, respectively. In conclusion, the quantitative analysis of the
      disaccharides produced by enzymatic digestion can be used in the direct
      quantitation of CS containing pharmaceutical formulations.

PMID- 15734154
TI  - Sol-gel-based solid-phase microextraction and gas chromatography-mass
      spectrometry determination of dextromethorphan and dextrorphan in human plasma.
AB  - A novel solid-phase microextraction (SPME) method was developed for isolation of
      dextromethorphan (DM) and its main metabolite dextrorphan (DP) from human plasma
      followed by GC-MS determination. Three different polymers, poly(dimethylsiloxane)
      (PDMS), poly(ethylenepropyleneglycol) monobutyl ether (Ucon) and polyethylene
      glycol (PEG) were synthesized as coated fibers using sol-gel methodologies. DP
      was converted to its acetyl-derivative prior to extraction and subsequent
      determination. The porosity of coated fibers was examined by SEM technique.
      Effects of different parameters such as fiber coating type, extraction mode,
      agitation method, sample volume, extraction time, and desorption condition, were
      investigated and optimized. The method is rapid, simple, easy and inexpensive and
      offers high sensitivity and reproducibility. The limits of detection are 0.010
      and 0.015 ng/ml for DM and DP, respectively. The precisions for both analytes are
      below 5% (n=5). The correlation coefficient was satisfactory (r(2)>0.99) for both
      DM and DP. Linear ranges were obtained from 0.03 ng/ml to 2 microg/ml for DM and
      from 0.05 ng/ml to 2 microg/ml for DP.

PMID- 15734155
TI  - Relationship between cucurbitacins reversed-phase high-performance liquid
      chromatography hydrophobicity index and basal cytotoxicity on HepG2 cells.
AB  - Drug development of cucurbitacins requires derivatives that have lower
      cytotoxicity. Therefore, the effect of structural modification on in vitro
      cytotoxicity has been investigated. Lipophilicity or chromatographic
      hydrophobicity index (CHI) was chosen as molecular property. CHI was determined
      by RP-HPLC in both aqueous acetonitrile and aqueous methanol. Compounds CHI range
      was wide and better defined in acetonitrile (CHI(ACN)=46-88 and 38-102) than in
      methanol (CHI(MeOH)=56-78). Higher resolution was achieved in acetonitrile, and
      higher precision on the shorter C18 column. Cucurbitacins cytotoxicity (IC(50))
      was measured on the hepatocyte-derived HepG2 cells. Strong relationship between
      CHI and logarithmic IC(50) was found. As a result, cytotoxicity increased
      linearly with increasing hydrophobicity (r>/=0.90). Other lipophilicity
      parameters, such as logP and ClogP were also estimated. Cytotoxicity correlated
      well with logP (r=0.95) and slightly with ClogP (r=0.74). The logP and ClogP data
      showed good correlation with CHI (r>0.92). Overall, alkylation of C1 hydroxyl,
      unsaturation of C1C2 bond, and acetylation of C25 hydroxyl increased both
      lipophilicity and cytotoxicity. This assay should prove useful for monitoring
      cucurbitacin homologues or other drug candidates for their cytotoxicity.

PMID- 15734156
TI  - High performance liquid chromatographic-mass spectrometric determination of
      ginsenoside Rg3 and its metabolites in rat plasma using solid-phase extraction
      for pharmacokinetic studies.
AB  - To support pharmacokinetic studies of ginsenosides, a novel method to
      quantitatively analyze ginsenoside Rg3 (Rg3), its prosapogenin ginsenoside Rh2
      (Rh2) and aglycone 20(S)-protopanaxadiol (ppd) in rat plasma was developed and
      validated. The method was based on gradient separation of ginsenosides present in
      rat plasma using high performance liquid chromatography (HPLC), followed by
      detection with electrospray ionization(ESI) mass spectrometry (MS) in negative
      ion mode with the mobile phase additive, ammonium chloride (500 microM).
      Differentiation of ginsenosides was achieved through simultaneous detection of
      the [M(+)Cl(-)] adduct of ginsenoside Rg3 and [M(+)Cl(-)] adducts of its
      deglycosylated metabolites Rh2 and ppd, and other ions after solid phase
      extraction (SPE). The /specific ions monitored were m/z 819.50 for Rg3, m/z
      657.35 for Rh2, m/z 495.40 for ppd and m/z 799.55 for the internal standard
      (digitoxin). The mean recoveries for Rg3, Rh2 and ppd were 77.85, 82.65 and
      98.33%, respectively using 0.1 ml plasma for extraction. The lower limits of
      quantification were 10.0, 2.0 and 8.0 ng/ml (equivalent to 0.1, 0.02 and 0.08 ng
      in each 10 microl injection onto the HPLC column) for Rg3, Rh2 and ppd,
      respectively. The method has been demonstrated to be highly sensitive and
      accurate for the determination of Rg3 and its metabolites in rat plasma.

PMID- 15734157
TI  - Determination of 14 benzodiazepines and hydroxy metabolites, zaleplon and
      zolpidem as tert-butyldimethylsilyl derivatives compared with other common
      silylating reagents in whole blood by gas chromatography-mass spectrometry.
AB  - The most common commercially available silylating reagents, N-methyl-N
      (trimethylsilyl)trifluoroacetamide (MSTFA), N,O-bis
      (trimethylsilyl)trifluoroacetamide+1% trimethylchlorosilane (BSTFA+1% TMCS) and N
      methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) were evaluated to
      achieve optimal derivatization conditions for analyzing various benzodiazepines
      based on gas chromatography-electron impact ionization-mass spectrometry (GC-EI
      MS). Sensitivity, repeatability, retention times and stability of the
      derivatives, as well as specificity of mass fragmentation, were studied in
      detail. Also other parameters affecting the derivatization chemistry of
      benzodiazepines are discussed. tert-Butyldimethylsilyl (TBDMS) derivatives proved
      to be more stable, reproducible and sensitive than corresponding trimethylsilyl
      (TMS) derivatives for the GC-EI-MS analysis of benzodiazepines. Based on the
      TBDMS derivatives, a rapid, reliable, sensitive and quantitative GC-MS method was
      developed for the determination of 14 benzodiazepines and two hydroxy
      metabolites, as well as two non-benzodiazepine hypnotic agents, zolpidem and
      zaleplon, using 50 microl of whole blood. The method was completely validated in
      terms of accuracy, intra- and interday precision, limit of detection (LOD), limit
      of quantitation (LOQ), linearity, selectivity and extraction efficiency; these
      were all within the required limits, except for the accuracy of nitrazepam at a
      medium concentration level.

PMID- 15734158
TI  - Determination of warfarin enantiomers and hydroxylated metabolites in human blood
      plasma by liquid chromatography with achiral and chiral separation.
AB  - An assay comprising two simple, selective and isocratic HPLC methods with UV
      detection was developed and validated for measuring warfarin enantiomers and all
      five warfarin monohydroxylated metabolites in patient blood plasma. Following
      liquid/liquid extraction from 1 ml of blood plasma a baseline separation of
      analytes was achieved on chiral (alpha(1) acid glycoprotein - AGP) and achiral
      (C(18)) column. Both methods were consistent (R.S.D.<6.9% for warfarin
      enantiomers and<8.9% for monohydroxylated metabolites) and linear (r>0.998). The
      limits of detection were 25 ng/ml for warfarin enantiomers, 25 ng/ml for 4'-, 10
      , 6- and 7-hydroxywarfarin, 35 ng/ml for 8-hydroxywarfarin and 50 ng/ml for
      racemic warfarin. In a clinical study in 204 patients, it was confirmed that the
      assay is appropriate for evaluation of influences of genetic polymorphisms,
      demographic factors and concomitant drug treatment on warfarin metabolism.

PMID- 15734159
TI  - Liquid chromatographic quantitation of the lactone and the total of lactone and
      carboxylate forms of 9-nitrocamptothecin in human plasma.
AB  - Simple and sensitive high-performance liquid chromatography (HPLC) assays were
      developed and validated for the quantitation of the investigational anticancer
      drug 9-nitrocamptothecin (9-NC) as the lactone form and as the total of the
      lactone(I) and carboxylate(II) forms in human plasma. For the assay of lactone
      form (9NC-lac), the analytical method involved a protein precipitation step with
      adding a mixture of cold acetonitril-chloroform (5:1 (v/v), -20 degrees C) to
      plasma sample that stabilized the pH-dependent conversion of I to II. After
      evaporation under gentle stream of nitrogen gas (40 degrees C) the dry extract
      was dissolved in mobile phase (pH 5.5). For determination of the total of the
      lactone and carboxylate forms of the drug (9NC-tot), plasma samples were
      deproteinated with cold acetonitril (-20 degrees C) acidified with perchloric
      acid (5%), which resulted in the conversion of the carboxylate into the lactone
      form. After centrifugation the upper solvent was evaporated (nitrogen, 40 degrees
      C) and the dry extract was dissolved in mobile phase (pH 3.5). All separations
      were performed on a RP-C(8) column, using a mixture of acetonitril-water as
      eluent (pH 3.5 for total form and pH 5.5 for lactone form) and UV detection. The
      presented assay was linear over a concentration range of 25-1500 ng/ml with lower
      limit of quantitation of 25 ng/ml for both 9NC-tot and 9NC-lac. Within-run and
      between-run precision was always less than 7.5% in the concentration range of
      interest. The reported assay method showed good characteristics of linearity,
      sensitivity, selectivity and precision allowing applying in pharmacokinetic
      studies.

PMID- 15734160
TI  - Simple and sensitive high performance liquid chromatographic method for the
      simultaneous quantitation of the lactone and carboxylate forms of topotecan in
      human plasma.
AB  - A selective and highly sensitive isocratic high performance liquid
      chromatographic (HPLC) method is described for simultaneous determination of
      lactone and carboxylate species of topotecan, in plasma. The method utilizes a
      protein precipitation step with cold methanol (-20 degrees C) for sample
      preparation followed by separation on a Novapack C(18) column using ammonium
      acetate buffer, acetonitrile and triethylamine (84:16:1.5, v/v) containing
      tetrabutyl ammonium hydrogen sulfate (TBAHS) (2 mM) with a pH of 5 as the mobile
      phase. The eluted peaks were detected by a fluorescence detector was set at an
      excitation wavelength of 380 nm and an emission wavelength of 527 nm. The method
      was validated in the range of lactone and carboxylate forms of topotecan
      concentrations from 0.05 to 75 ng/ml. Intra- and inter-day precision expressed by
      the relative standard deviation was less than 8.50% and inaccuracy did not exceed
      10% for lactone and carboxylate forms of topotecan. The limit of quantitation was
      0.05 ng/ml using 0.50 ml plasma. Stability studies in plasma and plasma extract
      indicated that topotecan is stable for at least 2 weeks at -70 degrees C.

PMID- 15734161
TI  - Quantitation of itopride in human serum by high-performance liquid chromatography
      with fluorescence detection and its application to a bioequivalence study.
AB  - A new method was developed for determination of itopride in human serum by
      reversed phase high-performance liquid chromatography (HPLC) with fluorescence
      detection (excitation at 291 nm and emission at 342 nm). The method employed one
      step extraction of itopride from serum matrix with a mixture of tert-butyl methyl
      ether and dichloromethane (70:30, v/v) using etoricoxib as an internal standard.
      Chromatographic separation was obtained within 12.0 min using a reverse phase YMC
      Pack AM ODS column (250 mm x 4.6 mm, 5 microm) and an isocratic mobile phase
      constituting of a mixture of 0.05% tri-fluoro acetic acid in water and
      acetonitrile (75:25, v/v) flowing at a flow rate of 1.0 ml/min. The method was
      linear in the range of 14.0 ng/ml to 1000.0 ng/ml. The lower limit of
      quantitation (LLOQ) was 14.0 ng/ml. Average recovery of itopride and the internal
      standard from the biological matrix was more than 66.04 and 64.57%, respectively.
      The inter-day accuracy of the drug containing serum samples was more than 97.81%
      with a precision of 2.31-3.68%. The intra-day accuracy was 96.91% or more with a
      precision of 5.17-9.50%. Serum samples containing itopride were stable for 180.0
      days at -70+/-5 degrees C and for 24.0 h at ambient temperature (25+/-5 degrees
      C). The method was successfully applied to the bioequivalence study of itopride
      in healthy, male human subjects.

PMID- 15734162
TI  - Determination of Salvinorin A in body fluids by high performance liquid
      chromatography-atmospheric pressure chemical ionization.
AB  - Salvinorin A was quantitated in human and rhesus monkey plasma, rhesus monkey
      cerebrospinal fluid, and human urine by negative ion LC-MS/APCI. The method for
      Salvinorin A has been fully validated, the LLOQ using FDA guidelines is 2 ng/mL
      for 0.5 mL plasma samples. The linear range was from 2 to 1000 ng/mL. Several
      derivatives in the Salvinorin family can also be analyzed by this method; d(3)
      Salvinorin A was prepared and used as internal standard. The metabolite
      Salvinorin B can be semi quantitatively determined. The method has been used to
      establish that Salvinorin B is the principal metabolite of Salvinorin A ex vivo
      and to establish the analytical method to study in vivo samples.

PMID- 15734163
TI  - Determination of glutathione and glutathione disulfide in hepatocytes by liquid
      chromatography with an electrode modified with functionalized carbon nanotubes.
AB  - Glutathione (GSH) and glutathione disulfide (GSSG) are important thiols, which
      provide defence against oxidative stress by scavenging free radicals or causing
      the reduction of hydrogen peroxide. The ratio GSH/GSSG is often used as a
      sensitive index of oxidative stress in vivo. In this paper, a direct
      electrochemical method using an electrode modified with functionalized carbon
      nanotubes as electrochemical detector (ED) for liquid chromatography (LC) was
      described. The electrochemical behaviors of GSH and GSSG on this modified
      electrode were investigated by cyclic voltammetry and it was found that the
      functionalized carbon nanotubes exhibited efficiently electrocatalysis on the
      current responses of GSH and GSSG. In LC-ED, both of the analytes showed good and
      stable current responses. The detection limit of GSH was 0.2 pmol on column and
      that of GSSG was 1.2 pmol on column, which were low enough for the analysis of
      real small samples. The method was sensitive enough to detect difference in
      concentration of GSH and GSSG in hepatocytes from animals with and without
      introduction of oxidation stress by glucose or hydrogenperoxide.

PMID- 15734164
TI  - Simultaneous determination of buprenorphine and its prodrug, buprenorphine
      propionate, by high-performance liquid chromatography with fluorescence
      detection: application to pharmacokinetic studies in rabbits.
AB  - A rapid, sensitive, precise and accurate high-performance liquid chromatographic
      assay with fluorescence detection was developed for the simultaneous
      determination of buprenorphine and buprenorphine propionate in human and animal
      blood. Buprenorphine propionate was also proven to be a prodrug of buprenorphine.
      It was comprised of only a one-step extraction procedure with ethyl acetate and
      normal-phase chromatography on a Betasil Silica column. The recoveries of
      buprenorphine and buprenorphine propionate were above 84%. Calibration graphs
      were linear for buprenorphine over the concentration range 2-1500 ng/ml and for
      buprenorphine propionate over the concentration range 20-1500 ng/ml with a
      coefficient of variation, both within- and between-day, or less than 10% at any
      level. The limits of quantitation of buprenorphine and buprenorphine propionate
      in human or animal blood were 2.0 and 20 ng/ml, respectively, based on a single
      to-noise ratio of 3. The method has been successfully applied to pharmacokinetic
      studies of buprenorphine and buprenorphine propionate in rabbits. The results
      demonstrated that buprenorphine propionate was rapidly and totally converted to
      its parent drug, buprenorphine, following intravenous administration.
      Buprenorphine propionate is a prodrug of buprenorphine.

PMID- 15734165
TI  - Concerns in the development of an assay for determination of a highly conjugated
      adsorption-prone compound in human urine.
AB  - Concerns in pre-analytical handling of urine samples are discussed using a new
      KDR kinase inhibitor, 3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2
      yl]-1H-quinolin-2-one (compound A), as an example of a case where high light
      sensitivity and low analyte recovery (high affinity for container surface) were
      found. The absence of these problems in plasma samples may be a result of the
      plasma protein content. Low recovery of the analyte from urine can be remedied by
      either changing the container or by using additives, such as bovine serum albumin
      (BSA) or non-ionic surfactant Tween-20. In the case of compound A, changing
      containers (polypropylene versus glass vial) or addition of BSA did bring analyte
      recovery up to 80%. However, the addition of 0.2% Tween-20 into urine quality
      controls (QCs) gave more than 95% analyte recovery, indicating effective
      reduction of analyte loss to the surface of containers. The urine assay using
      mixed-mode SPE and LC-MS/MS was not affected significantly by introducing Tween
      20 into the samples. The mean SPE extraction recovery was 68.4% and matrix
      suppression of ionization on MS was less than 8% at all analyte concentrations.
      The linear range of the calibration curve was 0.5-400 ng/mL on PE Sciex API 3000
      LC-MS/MS system. The assay intraday accuracy and precision were 92.1-104.8% and
      <4.2% (%CV), respectively. Urine QC samples, containing 0.2% Tween-20, gave
      excellent recovery after three cycles of freeze and thaw. Since analyte loss to
      its urine container surface is not unique to compound A (M. Schwartz, W. Kline,
      B. Matuszewski, Anal. Chim. Acta 352 (1997) 299-307; A.L. Fisher, E. DePuy, T.
      Shih, R. Stearns, Y. Lee, K. Gottesdiener, S. Flattery, M. De Smet, B. Keymeulen,
      D.G. Musson, J. Pharm. Biomed. Anal. 26 (2001) 739-752), we suggest an evaluation
      of the potential problem in the early stages of urine assay development to ensure
      reliable quantitation of analytes. The addition of Tween-20 can serve as a useful
      analytical tool to other analytes with similar situations.

PMID- 15734166
TI  - Validation study of a method for assaying DE-310, a macromolecular carrier
      conjugate containing an anti-tumor camptothecin derivative, and the free drug in
      human plasma by HPLC and LC/MS/MS.
AB  - DE-310 is a macromolecular carrier conjugate containing an anti-tumor
      camptothecin derivative, DX-8951, conjugated to a water-soluble polymer by means
      of a peptide spacer. New assay methods have been developed to determine the
      polymer-bonded DX-8951 conjugate, free DX-8951, and Glycyl-DX-8951 in human
      plasma. Solid-phase extraction was used to extract free DX-8951 and Glycyl-DX
      8951 from plasma, and LC/MS/MS (Method I) was used to determine the amount of
      each analyte. Protein precipitation was used to extract Conjugated DX-8951, which
      was then digested with thermolysin. HPLC (Method II) was used to determine the
      productive compound (Phenylalanyl-Glycyl-DX-8951). The lower limit of
      quantitation of DX-8951 was 50 pg/ml, of Glycyl-DX-8951 was 80 pg/ml, and of
      Conjugated DX-8951 was 100 ng/ml (as DX-8951 equivalent). Both methods showed
      satisfactory sensitivity, precision, and accuracy.

PMID- 15734167
TI  - Quantification of pravastatin in human plasma and urine after solid phase
      extraction using high performance liquid chromatography with ultraviolet
      detection.
AB  - A high performance liquid chromatography (HPLC) method for the estimation of
      pravastatin in human plasma and urine samples has been developed. The preparation
      of the samples was performed by automated solid phase extraction using clonazepam
      as internal standard. The compounds were separated by isocratic reversed-phase
      HPLC (C(18)) and detected at 239 nm. The method was linear up to concentrations
      of 200 ng/ml in plasma and 2000 ng/ml in urine. The intra-assay variability for
      pravastatin in plasma ranged from 0.9% to 3.5% and from 2.5% to 5.3% in urine.
      The inter-assay variability ranged from 9.1% to 10.2% in plasma and from 3.9% to
      7.5% in urine. The validated limits of quantification were 1.9 ng/ml for plasma
      and 125 ng/ml for urine estimation. These method characteristics allowed the
      determination of the pharmacokinetic parameters of pravastatin after
      administration of therapeutic doses.

PMID- 15734168
TI  - Development and characterization of an immobilized human organic cation
      transporter based liquid chromatographic stationary phase.
AB  - Membranes from a stably transfected cell line that expresses the human organic
      cation 1 transporter (hOCT1) have been immobilized on the immobilized artificial
      membrane (IAM) liquid chromatographic stationary phase to form the hOCT1(+)-IAM
      stationary phase. Membranes from the parent cell line that does not express the
      hOCT1 were also immobilized to create the hOCT1(-)-IAM stationary phase. Columns
      were created using both stationary phases, and frontal displacement
      chromatography experiments were conducted using [(3)H]-methyl phenyl pyridinium
      ([(3)H]-MPP(+)) as the marker ligand and MPP(+), verapamil, quinidine, quinine,
      nicotine, dopamine and vinblastin as the displacers. The K(d) values calculated
      from the chromatographic studies correlated with previously reported K(i) values
      (r(2)=0.9987; p<0.001). The data indicate that the hOCT1(+)-IAM column can be
      used for the on-line determination of binding affinities to the hOCT1 and that
      these affinities are comparable to those obtained using cellular uptake studies.
      In addition, the chromatographic method was able to identify a previously
      undetected high affinity binding site for MPP(+) and to determine that hOCT1
      bound (R)-verapamil to a greater extent than (S)-verapamil.

PMID- 15734169
TI  - Simple and rapid determination of serotonin and catecholamines in biological
      tissue using high-performance liquid chromatography with electrochemical
      detection.
AB  - Using the CNS of Lymnaea stagnalis a method is described for the rapid analysis
      of neurotransmitters and their metabolites using high performance liquid
      chromatography coupled with electrochemical detection. Tissue samples were
      homogenised in ice-cold 0.1 M perchloric acid and centrifuged. Using a C(18)
      microbore column the mobile phase was maintained at a flow rate of 100 microl/min
      and consisted of sodium citrate buffer (pH 3.2)-acetonitrile (82.5:17.5, v/v)
      with 2 mM decane-sulfonic acid sodium salt. The potential was set at +750 mV
      versus Ag|AgCl reference electrode at a sensitivity of 50 nA full scale
      deflection. The detection limit for serotonin was 11.86 ng ml(-1) for a 5 microl
      injection. Preparation of tissue samples in mobile phase reduced the response to
      dopamine and serotonin compared with perchloric acid. In addition it was found
      that the storage of tissue samples at -20 degrees C caused losses of dopamine and
      serotonin. As a result of optimising the sample preparation and mobile phase the
      total time of analysis was substantially reduced resulting in a sample
      preparation and assay time of 15-20 min.

PMID- 15734170
TI  - A sensitive liquid chromatographic method for the spectrophotometric
      determination of urinary trans,trans-muconic acid.
AB  - Benzene is a human carcinogen and its metabolite, urinary trans,trans-muconic
      acid (ttMA), is a biomarker for risk assessment. However, most of the existing
      methods were not sensitive enough for monitoring of low level exposure. This
      paper describes a HPLC-UV method for ttMA determination with enhanced selectivity
      and sensitivity. A 30 mg OasisMAX cartridge was used to clean-up 50 microl of
      urine sample and gradient elution was performed on a Zorbax SB-C(18) column (30
      degrees C). ttMA was detected at wavelength 263 nm using a UV diode array
      detector (DAD). The two mobile phases used were (A) 150 mM ortho-phosphoric acid
      containing of 9% (v/v) methanol; and (B) 125 mM ortho-phosphoric acid containing
      30% (v/v) acetonitrile. The method was validated with 61 urine samples collected
      from non-occupationally benzene exposed individuals and 14 quality control
      specimens from an international quality assessment scheme. The urinary ttMA
      concentrations (mean+/-S.D.microg/g creatinine) were 90+/-34 for smokers (n=26),
      49+/-39 for non-smokers (n=21) and 23+/-18 for non-smoking hospital staff (n=14).
      A correlation coefficient, r=0.99 was found with 14 external quality specimens
      for ttMA ranged from 0.4 to 6.8 mg/l. The recovery and reproducibility were
      generally over 90% and the detection limit was 5 microg/l.

PMID- 15734171
TI  - Solid-phase microextraction and chiral HPLC analysis of ibuprofen in urine.
AB  - A simple and rapid solid-phase microextraction method was developed for the
      enantioselective analysis of ibuprofen in urine. The sampling was made with a
      polydimethylsiloxane-divinylbenzene coated fiber immersed in the liquid sample.
      After desorptioning from the fiber, ibuprofen enantiomers were analyzed by HPLC
      using a Chiralpak AD-RH column and UV detection. The mobile phase was made of
      methanol-pH 3.0 phosphoric acid solution (75:25, v/v), at a flow rate of 0.45
      mL/min. The mean recoveries of SPME were 19.8 and 19.1% for (-)-R-ibuprofen and
      (+)-(S)-ibuprofen, respectively. The method was linear at the range of 0.25-25
      microg/mL. Within-day and between-day assay precision and accuracy were below 15%
      for both ibuprofen enantiomers at concentrations of 0.75, 7.5 and 20 microg/mL.
      The method was tested with urine quality control samples and human urine
      fractions after administration of 200 mg rac-ibuprofen.

PMID- 15734172
TI  - Application of the standard addition approach for the quantification of urinary
      benzene.
AB  - Urinary benzene is used as biomarker of exposure to evaluate the uptake of this
      solvent both in non-occupationally exposed population and in benzene-exposed
      workers. The quantitative determination of benzene in urine is carried out in a
      three steps procedure: urine collection, sample analysis by head space/solid
      phase microextraction/gas chromatography/mass spectrometry and analyte
      quantification. The adopted quantification method influences the initial step,
      hence the whole procedure. Two quantification approaches were compared as regards
      precision and accuracy: the calibration curves and the standard addition method.
      Even if calibration curves obtained by using urine samples from different
      subjects were always linear, their slopes and intercepts showed noteworthy
      variations, attributable to the influence of the biological matrix on benzene
      recovery. The standard addition method showed to be more suitable for
      compensating matrix effects, and a three-point standard addition protocol was
      used to quantify benzene in urine samples of 11 benzene-exposed workers (smokers
      and non-smokers). Urine from occupationally exposed workers was collected before
      and after work-shift. Besides urinary benzene, the applicability of the method
      was verified by measuring the urinary concentration of the S-phenylmercapturic
      acid, a specific benzene metabolite, generally adopted as biomarker in biological
      monitoring procedures. A similar trend of concentration levels of both analytes
      measured in urine samples collected before work-shift with respect to the after
      work-shift ones was found, showing the actual applicability of the standard
      addition method for biological monitoring purposes.

PMID- 15734173
TI  - Sensitive capillary chromatography mass spectrometric methods for the
      determination of salcatonin in human biological matrices.
AB  - New methods employing capillary liquid chromatography in combination with time-of
      flight mass spectrometry (microLC-TOF/MS) were developed for the rapid
      determination of salcatonin in human urine and plasma. The present approaches
      utilize (13)C(6)-leucine (19)-labeled salcatonin as internal standard, small
      matrix volumes and simple sample preparation procedures. They allow TOF/MS to be
      used as a highly selective detector for providing accurate quantitation of
      salcatonin. Data acquisition was performed in enhanced mode optimizing the signal
      for the triply charged species of salcatonin and its internal standard. We
      demonstrate that the determination of salcatonin is straightforward and reliable
      and can be performed with excellent linearity (R(2)>0.999), precision and
      accuracy over the concentration ranges of 2.9-290 pmol/mL in human urine, and 7.3
      730 pmol/mL in human plasma.

PMID- 15734174
TI  - Determination of urinary succinylacetone by capillary electrophoresis for the
      diagnosis of tyrosinemia type I.
AB  - The presence of succinylacetone in urine or blood or amniotic fluid is
      pathognomonic of an inherited metabolic disorder, named tyrosinemia type I. We
      developed a capillary electrophoretic method for the fast analysis of
      succinylacetone in urine samples. The separation was performed at reversed
      polarity mode using either a cationic surfactant as the buffer additive, or a
      capillary coated with a positively charged polyelectrolyte. Under these
      conditions, urine samples were directly injected to the capillary without any
      pretreatment step. The utility of the method was demonstrated by the
      identification of succinyacetone in urine from patients with hereditary
      tyrosinemia type I. For all patients, diagnostic peaks at the expected migration
      times were detected. The developed method is rapid, simple, inexpensive, and
      suitable for the determination of succinylacetone in clinical urine samples.

PMID- 15734176
TI  - Income and child maltreatment.

PMID- 15734177
TI  - The results of randomized clinical trials move the field forward.

PMID- 15734179
TI  - Treating sexually abused children: 1 year follow-up of a randomized controlled
      trial.
AB  - OBJECTIVE: To measure the durability of improvement in response to two
      alternative treatments for sexually abused children. METHOD: Eighty-two sexually
      abused children ages 8-15 years old and their primary caretakers were randomly
      assigned to trauma-focused cognitive-behavioral therapy (TF-CBT) or non-directive
      supportive therapy (NST) delivered over 12 sessions; this study examines
      symptomatology during 12 months posttreatment. DATA ANALYSIS: Intent-to-treat and
      treatment completer repeated measures analyses were conducted. RESULTS: Intent-to
      treat indicated significant group x time effects in favor of TF-CBT on measures
      of depression, anxiety, and sexual problems. Among treatment completers, the TF
      CBT group evidenced significantly greater improvement in anxiety, depression,
      sexual problems and dissociation at the 6-month follow-up and in PTSD and
      dissociation at the 12-month follow-up. CONCLUSION: This study provides
      additional support for the durability of TF-CBT effectiveness.

PMID- 15734178
TI  - Income, family characteristics, and physical violence toward children.
AB  - OBJECTIVE: This paper discusses the ways in which existing microeconomic theories
      of partner abuse, intra-family bargaining, and distribution of resources within
      families may contribute to our current understanding of physical child abuse. The
      empirical implications of this discussion are then tested on data from the 1985
      National Family Violence Survey (NFVS) in order to estimate the effects of
      income, family characteristics, and state characteristics on physical violence
      toward children. METHODOLOGY: The sample consists of 2,760 families with children
      from the NFVS. Probit and ordered probit models are used to explore relationships
      between income, family characteristics, state characteristics, and physical
      violence toward children among single-parent and two-parent families. RESULTS: In
      both single-parent and two-parent families, depression, maternal alcohol
      consumption, and history of family violence affect children's probabilities of
      being abused. Additionally, income is significantly related to violence toward
      children in single-parent families. CONCLUSIONS: These results reinforce earlier
      findings that demographic characteristics, maternal depression, maternal alcohol
      use, and intra-family patterns of violence may largely contribute to child abuse.
      This research also suggests that income may play a substantially more important
      role in regard to parental violence in single-parent families than in two-parent
      families.

PMID- 15734180
TI  - Why child maltreatment researchers should include children's disability status in
      their maltreatment studies.

PMID- 15734181
TI  - Sexual abuse perpetrated by adult and juvenile females: an ultimate attempt to
      resolve a conflict associated with maternal identity.
AB  - OBJECTIVE: The purpose of this article is to report the descriptive and
      phenomenological aspects of adult females (AF) and juvenile females (JF) who
      sexually abuse children and adolescents. A major focus is to study the relational
      problems during childhood and adulthood of this specific population and how they
      echo the relational aspects of their own victimization. METHODOLOGY: Since 1992,
      clinical and evaluative data were collected from a sample of 13 AF and 15 JF who
      had committed sexual abuse. The subjects were evaluated in the program for adult
      and adolescent sex offenders at the outpatient clinic of the Centre de
      Psychiatrie Legale de Montreal (affiliated with the Institut Philippe Pinel de
      Montreal). The data were collected by a multidisciplinary team of clinicians:
      psychiatrists, psychologists, criminologists and sexologists. A team of two or
      three clinicians who utilized a standardized interview grid evaluated each
      subject. RESULTS: Mean age at the time of the evaluation was 36.2 years (SD=9.28)
      for the AF and 14.7 years (SD=1.39) for the JF. A considerable percentage of the
      sexual abuses occurred in an intra-familial context for both groups (92.3% of the
      AF; 53.3% of the JF). Half of the AF not only committed sexual but also physical
      abuse of their victims. In addition, the precocious and repetitive dimension of
      the sexual abuses perpetrated by 33.3% of the JF was noted. CONCLUSION: This
      descriptive study reports a set of problematic relationships and a history of
      victimization among AF and JF. The history of the relationship with their parents
      frequently revealed that for JF, the father was absent or not very involved and
      for AF the father was sexually and physically abusive. On the other hand, a
      disturbed mother-child relationship among both AF and JF sexual abusers
      highlights an important conflict.

PMID- 15734182
TI  - Maternal use of physical punishment in response to child misbehavior:
      implications for child abuse prevention.
AB  - OBJECTIVE: The objective was to examine the roles of cognition and affect in
      maternal use of physical punishment. METHOD: Through a review of the literature,
      distal and proximal predictors (cognitive and affective) of physical punishment
      use were identified. One hundred and ten mothers of 3-year-old children were
      interviewed regarding two disciplinary situations that occurred during the
      previous 2-week period that elicited their strongest reactions: one which
      resulted in the use of physical punishment (if this occurred) and one which did
      not. The individual and combined contributions of the predictors of physical
      punishment use were analyzed through logistic regression. RESULTS: The predictors
      of physical punishment following individual analyses were: maternal attitude
      toward physical punishment, maternal perception of the seriousness and intent of
      the child misbehavior, and maternal anger in response to the child misbehavior.
      Through multivariate analysis 54% of the variance in physical punishment use was
      explained. CONCLUSIONS: Both cognitive and affective factors affect the decision
      to use physical punishment with children. These findings can be useful in
      establishing parenting educational programming that is directed at decreasing the
      rates of physical punishment and subsequently child physical abuse.

PMID- 15734183
TI  - Child abuse: Bahrain's experience.

PMID- 15734184
TI  - Do pediatric chief residents recognize details of prepubertal female genital
      anatomy: a national survey.
AB  - OBJECTIVE: To evaluate how well a group of recently trained pediatric chief
      residents could label anatomic structures on two different photographs of female
      prepubertal genitalia. Additionally, the study sought to explore aspects of
      pediatric training in sexual abuse and clinical practice issues surrounding the
      routine genital examination. METHOD: A 38-item questionnaire was mailed to
      pediatric chief residents at all of the officially listed pediatric residency
      training programs in the continental US. Comparisons were made between this study
      and the responses to two previous surveys, which asked a more heterogeneous group
      of physicians to label one of the photographs used in the study. The second
      photograph was added because of its improved clarity of each anatomic structure
      when compared to the first photograph used in the previous studies. The study
      also asked about clinical practice issues surrounding the prepubertal genital
      examination. RESULTS: An overall response rate of 73% was achieved and analysis
      was done on 139 respondents. One-half of chief residents thought that their
      training during residency on sexual abuse was inadequate for practice. Sixty-four
      percent of chief residents correctly labeled the hymen on the photograph used in
      the previous studies, which was not significantly different from the 62% and 59%
      of physicians who correctly labeled the hymen in the previous surveys. In the
      second photograph, which more clearly displayed the various anatomic structures,
      71% correctly labeled the hymen. CONCLUSION: Pediatric chief residents reported
      variable amounts of training on issues pertaining to child sexual abuse during
      residency, think that this time was inadequate, and, while doing slightly better
      than a more diverse group of previously studied physicians, did not achieve 100%
      accuracy in identifying basic genital structures correctly on two different
      photographs.

PMID- 15734185
TI  - A multivariate analysis of the accumulation and fractionation of major and trace
      elements in agricultural soils in Hidalgo State, Mexico irrigated with raw
      wastewater.
AB  - We evaluated the accumulation and distribution of major and trace elements in
      agricultural soils of District 03 (DR03) in the State of Hidalgo, Mexico,
      irrigated with raw wastewaters for an average of 20 years. Samples of topsoils (0
      30 cm depth) were extracted using a modified Tessier method. Total concentrations
      of the species tested were in the ranges of 675-1176 mg K kg(-1), 277.9-1001 mg
      Na kg(-1), 6,708-81,854 mg Ca kg(-1), 23,800-106,974 mg Mg kg(-1), 9.2-123.8 mg B
      kg(-1), 0.6-1.9 mg Cd kg(-1), 11.6-27.4 mg Cr kg(-1), 3.9-47.0 mg Pb kg(-1).
      Concentrations of As and Hg were very low. Concentrations of total Cd, Cr and Pb
      were generally below the maximum permissible levels set by the regulations of the
      European Union except for cadmium, which was in the middle of the maximum
      European range allowed for two soils. Regarding lead, one soil (S5) could reach
      the maximum permissible level of the EU in 6 more years of continued irrigation.
      On the other hand, contents of Pb in the most mobile fractions ("e" in this work)
      were significant (range: 3-28%). This distribution translated into concentrations
      of soluble plus exchangeable lead of approximately 2 mg Pb kg(-1) in three of six
      soils, significantly higher than the Swiss tolerance limit of 1.0 mg Pb kg(-1)
      for mobile fractions of lead in soils. Multivariate analysis of the data (Pearson
      correlation and principal component analysis) quantitatively confirmed that: (i)
      there is a strong covariance between boron contents and several variables
      representing the salinity of soils (electrolytic conductivity, a variety of
      alkaline and alkaline-earth total and fraction concentrations). It appears that
      there is a problem with high boron content in soils, although the salinity is
      high only for one of the soils (S3); (ii) a significant correlation among
      irrigation time, lead content (total, fraction easily exchangeable and bound to
      organic matter and sulfides) and organic carbon in soils was found; (iii) another
      association among irrigation time, total contents of cadmium, chromium and boron,
      and organic carbon was observed.

PMID- 15734186
TI  - Distribution of trace elements in tissues of two shrimp species from the Persian
      Gulf and roles of metallothionein in their redistribution.
AB  - This study investigates the distribution of three trace elements (Cd, Cu and Zn)
      in tissues (exoskeleton, abdominal muscle and hepatopancreas) of two shrimp
      species (Penaeus merguiensis and Penaeus semisulcatus). Special emphasis in this
      study was placed on evaluating the effects of storage conditions on
      redistribution of the elements and moreover the potential roles of
      metallothionein in tissue redistribution. The specimens were collected from the
      northern part of Persian Gulf during September 2001 and January 2002. The
      concentrations of metals in the tissues were measured using an Inductively
      Coupled Plasma-Atomic Emission Spectrophotometer (ICP-AES) and an ICP-Mass
      Spectrometer (ICP-MS). Metallothionein levels were determined using Differential
      pulse polarography. Results show a similar hierarchy for Cd and Cu concentrations
      among different tissues as follows: hepatopancreas>exoskeleton>muscle; and for
      Zn, the hepatopancreas again contained the highest levels, though there were not
      any significant differences in Zn concentrations between muscle and exoskeleton.
      Significant differences were found between the species in the case of Cd and Zn
      concentrations. Cd and Zn levels in P. semisulcatus were markedly higher than in
      P. merguiensis. In general, there were highly significant differences among the
      storage conditions from accumulation the selected trace elements and
      metallothionein in both species point of view, but in most cases, no significant
      differences could be observed among the fresh, refrigerated and frozen specimens
      of P. semisulcatus. In regards to Zn and Cu accumulation in edible (muscle)
      tissues of P. merguiensis, optimum conditions for frozen storage is -30 degrees C
      as ice-frozen, and in terms of short-term storage, 1-day refrigeration is
      recommended. The redistribution of Zn and Cu during the storage period can be
      attributed to the role of metallothionein in their transport from organ(s) to
      muscle during storage. The variations in pH values measured in the muscle of P.
      merguiensis in different storage conditions showed a similar trend with
      metallothionein, Zn and Cu. In contrast, it appears that cadmium is transported
      from muscle to the other tissues. Exoskeleton is probably one of the recipient
      tissues of cadmium. The inter-elemental relationships were assessed for each
      species, separately. A significant positive relationship was observed between the
      concentrations of Zn and metallothionein in P. semisulcatus, whereas in P.
      merguiensis, Cd concentrations decreased significantly with increasing
      metallothionein. Highly significant differences between the sexes in Cu and Zn
      contents could be detected. The differences between the sexes in the levels of Zn
      and Cu were significantly greater in P. semisulcatus. Highly significant size
      related differences were found in the levels of Cd, Cu and metallothionein in the
      selected tissues of the shrimp species. Comparison between the mean
      concentrations of the elements in muscle tissue and existing guidelines indicate
      that in nearly all cases, the concentrations were well below permissible levels
      for human consumption. The only exception was observed regarding mean values of
      Cd, which was somewhat greater than some of the recommended levels.

PMID- 15734187
TI  - The effects of air pollution and meteorological parameters on respiratory
      morbidity during the summer in Sao Paulo City.
AB  - Effects of meteorological variables and air pollutants on child respiratory
      morbidity are investigated during two consecutive summers (December-March
      1992/1993 and 1993/1994) at the Metropolitan Area of Sao Paulo (MASP), Brazil.
      The MASP, with almost 17 million inhabitants, is considered the most populous
      region in South America. Due to warmer temperatures, increased rainfall and
      consequent low levels of air pollutants during the summer compared to winter,
      less attention has been paid to epidemiological studies during this season,
      especially in tropical urban areas such as Sao Paulo. In the present work,
      principal component analysis (PCA) is applied to medical end environmental data
      to identify patterns relating child morbidity, meteorological variables and air
      pollutants during the summer. The following pollutant concentrations are
      examined: SO2, inhalable particulate matter (PM10), and O3. The meteorological
      variables investigated are air temperature, water vapor (water vapor density) and
      solar radiation. Although low correlation between respiratory morbidity and
      environmental variables are, in general, observed for the entire dataset, the PCA
      method indicates that child morbidity is positively associated with O3 for the
      1992/1993 summer. This pattern is identified in the third principal component
      (PC3), which explains about 19% of the total variance of all data in this summer.
      However, the 1993/1994 summer shows a more complex association between both
      groups, suggesting stronger ties with meteorological variables. Marked changes in
      synoptic conditions from the end of January to end of March of the 1993/1994
      summer seem to have played an important role in modulating respiratory morbidity.
      A detailed examination of meteorological conditions in that period indicates that
      prefrontal (postfrontal), hot (cold) and dry (wet) days favored the observed
      decrease (increase) of respiratory morbidity.

PMID- 15734188
TI  - Chlorpyrifos in surface waters before and after a federally mandated ban.
AB  - Samples collected from rural and urban streams in the City of Denton, Texas, USA
      were analyzed for the organophosphorus pesticides diazinon and chlorpyrifos
      during the years preceding and following a United States Environmental Protection
      Agency ban on many chlorpyrifos uses. A network of 70 monitoring stations, based
      mainly on topography and hydrological considerations, were established within the
      three main watersheds of Denton. Monitoring stations were sampled monthly from
      March through August during periods of normal flow (baseflow), resulting in a
      total of 308 samples and 311 samples collected during 2001 and 2002,
      respectively. Pesticide concentrations were determined using commercially
      available enzyme-linked immunosorbent assays (ELISA) specific for each pesticide.
      Results from this temporally and spatially dense monitoring effort were used to
      illustrate the impacts of a ban on most chlorpyrifos sales that was imposed in
      December 2001. The total number of samples exhibiting concentrations above method
      lower limits of detection (LLD) decreased between 2001 and 2002 for both
      chlorpyrifos and diazinon. The total number of sites exhibiting at least one
      sample with concentrations above the LLD for chlorpyrifos, however, significantly
      decreased (Fisher's exact test, p<<0.0001, n=70) when comparing 2001 (before the
      ban) with 2002 (after the ban). Similar analyses indicated no significant
      difference (Fisher's exact test, p=0.50, n=70) in the number of sites exhibiting
      detectable diazinon concentration between 2001 and 2002. Our results indicate
      that the cessation of retail chlorpyrifos sales at the end of 2001 resulted in a
      highly significant decrease in the surface water occurrences of this pesticide
      during 2002.

PMID- 15734189
TI  - The speciation and bioavailability of mercury in sediments of Haihe River, China.
AB  - Twenty-one sediment samples in 11 sites along the Haihe River and Dagu Drainage
      River, Tianjin, China, were analyzed to investigate the pollution status and
      bioavailability of mercury (Hg). The results showed that the Haihe River was
      slightly polluted with Hg when flowing through Tianjin city. On the contrary, the
      sediments collected from Dagu Drainage River, an important drainage river in
      Tianjin, were found to have very high Hg concentrations and the highest
      concentration reached 8779.1 ng g(-1) (dry weight). The methylmercury (MeHg)
      concentrations accounted for 0.1-2.4% (average: 0.9%) of total mercury (HgT) and
      were strongly influenced by HgT (r=0.91, p=0.99, n=20) and total organic carbon
      (TOC; r=0.76, p=0.99, n=20) contents in sediments. Moreover, a five-step
      sequential selective extraction (SSE) procedure was used to study the
      bioavailability of Hg in sediments. The mercury in sediments existed mainly as
      element Hg and mercury sulfide, which accounted for 46.5% and 39.0% of HgT,
      respectively. The percentage of exchangeable Hg (defined as water soluble Hg plus
      'human stomach acid' soluble Hg) was only 0.1-4.6%. The distribution of
      exchangeable Hg showed an obvious difference to that of HgT, indicating that the
      HgT concentrations were absolutely insufficient to evaluate the risk of Hg in
      sediments.

PMID- 15734190
TI  - Polybrominated diphenyl ethers, polychlorinated biphenyls and organochlorine
      pesticides in sediment cores from the Western Scheldt river (Belgium): analytical
      aspects and depth profiles.
AB  - A rapid and simple analytical method for the determination of organochlorines,
      such as polychlorinated biphenyls (PCBs) and selected organochlorinated
      pesticides (OCPs) and organobromines, such as polybrominated diphenyl ethers
      (PBDEs), in sediment samples was optimised using CRM 536 (PCBs in freshwater
      sediment). The method involved a hot Soxhlet extraction that reduced the
      extraction time to 2 h. Elemental sulphur, which is present in sediments and may
      interfere during the analysis, was removed by means of copper powder added to the
      sediment during extraction and into the clean-up cartridge. The analysis of PCBs
      and OCPs was accomplished by gas chromatography with electron capture or mass
      spectrometric detection. Similar quantitative results for PCB congeners in CRM
      536 were obtained using a 50-m capillary column and a 10-m narrow bore column
      suited for fast analysis. The analysis of PBDEs was done by mass spectrometry in
      negative chemical ionisation mode. Concentrations of organic pollutants in two
      sediment cores (approximately 50 cm depth) from the Scheldt river (south of
      Antwerp, Belgium) showed a relative steady state for PCBs and DDTs, with a slight
      decrease in the top layers, suggesting a slight decline in their concentrations
      due to restrictions in their usage. On the contrary, PBDEs were showing an
      increase in their concentrations in the top layers (up to 270 and 8400 ng/g dry
      weight for sum of tri- to hexa-BDE congeners and for BDE 209, respectively). This
      suggests an increasing trend in the concentrations of PBDEs in the Belgian
      environment.

PMID- 15734191
TI  - Causation in risk assessment and management: models, inference, biases, and a
      microbial risk-benefit case study.
AB  - Causal inference of exposure-response relations from data is a challenging aspect
      of risk assessment with important implications for public and private risk
      management. Such inference, which is fundamentally empirical and based on
      exposure (or dose)-response models, seldom arises from a single set of data;
      rather, it requires integrating heterogeneous information from diverse sources
      and disciplines including epidemiology, toxicology, and cell and molecular
      biology. The causal aspects we discuss focus on these three aspects: drawing
      sound inferences about causal relations from one or more observational studies;
      addressing and resolving biases that can affect a single multivariate empirical
      exposure-response study; and applying the results from these considerations to
      the microbiological risk management of human health risks and benefits of a ban
      on antibiotic use in animals, in the context of banning enrofloxacin or
      macrolides, antibiotics used against bacterial illnesses in poultry, and the
      effects of such bans on changing the risk of human food-borne campylobacteriosis
      infections. The purposes of this paper are to describe novel causal methods for
      assessing empirical causation and inference; exemplify how to deal with biases
      that routinely arise in multivariate exposure- or dose-response modeling; and
      provide a simplified discussion of a case study of causal inference using
      microbial risk analysis as an example. The case study supports the conclusion
      that the human health benefits from a ban are unlikely to be greater than the
      excess human health risks that it could create, even when accounting for
      uncertainty. We conclude that quantitative causal analysis of risks is a
      preferable to qualitative assessments because it does not involve unjustified
      loss of information and is sound under the inferential use of risk results by
      management.

PMID- 15734192
TI  - Fate of glutaraldehyde in hospital wastewater and combined effects of
      glutaraldehyde and surfactants on aquatic organisms.
AB  - Glutaraldehyde (GA), an aliphatic dialdehyde disinfectant, and surfactants, one
      of the major components of detergents, are widely used in hospitals in order to
      eliminate pathogenic organisms causing nosocomial infectious diseases. After
      their use, disinfectants and surfactants reach the wastewater network together.
      The discharge of chemical compounds from hospital activities into wastewater is
      also a well-known problem, causing pollution of water resources and constituting
      an ecological risk for aquatic organisms. In this study, the chemistry and
      toxicology of GA and surfactant mixtures were reviewed in order to estimate their
      fate in aquatic ecosystems. Furthermore, their joint effects on aquatic organisms
      were experimentally assessed in the laboratory. A simple model of the additive
      joint action of toxicants was used to determine combined acute toxicity effects
      on the bacteria luminescence and Daphnia mobility of three mixtures containing GA
      at 1.5 x EC50 24 h [in mg/L] on Daphnia and anionic, cationic and nonionic
      surfactants at twice their critical micellar concentration (CMC). The mixture of
      GA and a cationic surfactant gave an EC50 30 min on Vibrio fischeri of 0.158%,
      with a concentration of 0.04 mg GA/L and 1.04 mg CTAB/L, which provided an
      additive action. The interaction between GA and an anionic surfactant on V.
      fischeri produced an antagonistic joint action with an EC50 30 min of 3.95%,
      containing 1.06 mg GA/L and 33.2 mg SDS/L. A synergistic action with an EC50 30
      min of 8.4% on V. fischeri was observed for the mixture containing GA and a
      nonionic surfactant. Antagonistic interactions were observed for the joint action
      between GA and the surfactants studied on Daphnia. The mixture of GA and CTAB was
      more toxic (EC50 24 h=0.02%) than the two other mixtures (EC50 24 h GA+SDS=6%;
      EC50 24 h GA+TX 100=10%). This study provides new data on the toxicity of certain
      hospital pollutants entering the aquatic environment and detected in surface and
      groundwaters. It is necessary to study the joint effects of GA and surfactant
      mixtures following chronic and sublethal standard bioassays in order to estimate
      the contribution of the additive joint action models in assessing the
      environmental risk of hospital wastewater (HW).

PMID- 15734193
TI  - Using the WTO/TBT enquiry point to monitor tendencies in the regulation of
      environment, health, and safety issues affecting the chemical industry.
AB  - The growing importance of technical regulation affecting the use and sale of
      chemical products is a topic of interest not only for the chemical industry, but
      also for governments, nongovernmental organizations, consumers, and interested
      communities. The results of such regulation on behalf of the environment, health
      and safety of individuals, as well as its economic effects on industrial
      activity, are well understood in the United States and recently in the European
      Union. In less developed countries, however, the general level of public
      understanding of these issues is still minimal. It is common knowledge that the
      so-called "regulatory asymmetry" between countries at different levels of
      development contributes to the establishment of technical barriers to trade. Such
      asymmetries, however, also have other impacts: the displacement of polluting
      industrial sectors to countries which have less demanding regulations, the
      concentration of unsafe and harmful environmental conditions in certain parts of
      the globe, and the competitive disadvantage for industries located in countries
      where control is more rigid. This study analyses information on a wide range of
      technical regulations issued by World Trade Organization (WTO) members, and
      focuses on those regulations that affect the chemical industry. This information
      is available through the WTO Enquiry Points, organizations created in each
      country to administrate the Technical Barriers to Trade Agreement (TBT). This
      article consists of an analysis of 4,301 notifications of technical regulations
      by WTO member states in the 7-year period following the establishment of the WTO
      in 1995. Starting from this mass of information, 585 notifications that affect
      the circulation or use of chemical products were isolated. Of this group, 71%
      refer to only 15 countries. This group of notifications was further classified
      according to their motivation (the environment, health, safety), by the type of
      product affected (medications, fuels, hazardous products, etc.), by the type of
      country where it was established (developed, emerging or developing) and the
      existing conformity assessment mechanism (prohibition, licenses, certification,
      labeling, etc.). Beyond identifying tendencies in specific industrial sectors,
      the notifications studied here reach more than 100 chemical products, substances,
      preparations and other materials, which are subject to various levels of
      restrictions in different parts of the globe because of their composition or
      adverse reactions during their life cycles.

PMID- 15734194
TI  - Hazardous waste, impact on health and environment for development of better waste
      management strategies in future in India.
AB  - Industry has become an essential part of modern society, and waste production is
      an inevitable outcome of the developmental activities. A material becomes waste
      when it is discarded without expecting to be compensated for its inherent value.
      These wastes may pose a potential hazard to the human health or the environment
      (soil, air, water) when improperly treated, stored, transported or disposed off
      or managed. Currently in India even though hazardous wastes, emanations and
      effluents are regulated, solid wastes often are disposed off indiscriminately
      posing health and environmental risk. In view of this, management of hazardous
      wastes including their disposal in environment friendly and economically viable
      way is very important and therefore suggestions are made for developing better
      strategies. Out of the various categories of the wastes, solid waste contributes
      a major share towards environmental degradation. The present paper outlines the
      nature of the wastes, waste generating industries, waste characterization, health
      and environmental implications of wastes management practices, steps towards
      planning, design and development of models for effective hazardous waste
      management, treatment, approaches and regulations for disposal of hazardous
      waste. Appraisal of the whole situation with reference to Indian scenario is
      attempted so that a better cost-effective strategies for waste management be
      evolved in future.

PMID- 15734195
TI  - Ecological Sanitation--a way to solve global sanitation problems?
AB  - Today about 2.4 billion people in rural and urban areas do not have access to
      adequate sanitation services. Within 20 years, it is expected that an additional
      2 billion will live in towns and cities, mainly in developing countries,
      demanding sanitation. Still over 90% of sewage in developing countries is
      discharged untreated, polluting rivers, lakes and coastal areas. Conventional
      sanitation concepts, based on flush toilets, a water wasting technology, are
      neither an ecological nor economical solution in both industrialized and
      developing countries. The water-based sewage systems were designed and built on
      the premises that human excreta are a waste; suitable only for disposal and that
      the environment is capable of assimilating this waste. A sanitation system that
      provides Ecological Sanitation (EcoSan) is a cycle--a sustainable, closed-loop
      system, which closes the gap between sanitation and agriculture. The EcoSan
      approach is resource minded and represents a holistic concept towards
      ecologically and economically sound sanitation. The underlying aim is to close
      (local) nutrient and water cycles with as less expenditure on material and energy
      as possible to contribute to a sustainable development. Human excreta are treated
      as a resource and are usually processed on-site and then treated off-site. The
      nutrients contained in excreta are then recycled by using them, e.g., in
      agriculture. EcoSan is a systemic approach and an attitude; single technologies
      are only means to an end and may range from near-natural wastewater treatment
      techniques to compost toilets, simple household installations to complex, mainly
      decentralised systems. These technologies are not ecological per se but only in
      relation to the observed environment. They are picked from the whole range of
      available conventional, modern and traditional technical options, combining them
      to EcoSan systems. The paper presents an introduction to EcoSan principles and
      concepts including re-use aspects (available nutrients and occurring risks), and
      case studies of EcoSan concepts in both industrialized and developing countries.

PMID- 15734196
TI  - Pollution by nitrogen oxides: an approach to NO(x) abatement by using sorbing
      catalytic materials.
AB  - This article summarises the abatement of NO(x) pollution by using sorbing
      catalytic materials with special relevance to the challenge presented in fixed
      installations sources. A general vision of the origins of the different
      pollutants, with emphasis on nitrogen oxides formation, is presented as
      introduction. The impact of NO(x) pollution comprises additionally a quick view
      of its toxicity and environmental effects. Actual solutions are presented
      especially the case of the selective catalytic reduction (SCR) process with its
      advantages and difficulties. The new concepts for NO(x) abatement are also
      analysed. In such a way, updated information on solid sorbents for NO(x) removal
      is provided by including metal oxides, spinelles, perovskites, double-layered
      cuprates, zeolites, carbonaceous materials, heteropolyacids (HPAs), and supported
      heteropolyacids. The possibility of reducing those sorbed NO(x) is also
      underlined. Sorption mechanisms are analysed and clarified by emphasising
      convergence and disagreement points.

PMID- 15734197
TI  - Molecular predictor and promising target: will EGFR now become a star in
      radiotherapy?

PMID- 15734198
TI  - Different classes of EGFR inhibitors may have different potential to improve
      local tumour control after fractionated irradiation: a study on C225 in FaDu
      hSCC.
AB  - BACKGROUND AND PURPOSE: Previous experiments reported from this laboratory have
      shown that simultaneous application of the selective epidermal growth factor
      receptor tyrosine kinase (EGFR-TK) inhibitor BIBX1382BS during fractionated
      irradiation significantly prolonged growth delay of FaDu human squamous cell
      carcinoma but did not improve local tumour control. The present study
      investigates the effect of the EGFR monoclonal antibody (mAb) C225 on local
      tumour control of FaDu tumours after combined treatment with single dose and
      fractionated irradiation to address whether different classes of EGFR inhibitors
      have different potential to improve the outcome of radiotherapy in the same
      tumour model. MATERIAL AND METHODS: In unirradiated tumours, C225 was given
      either once or 4 times i.p. to the nude mice. Irradiation experiments were
      performed with graded single doses under clamp hypoxic conditions or with 30
      fractions in 6 weeks with graded total doses under ambient blood flow. C225 was
      given 6h before or 6 h before and 2, 5 and 7 days after single dose irradiation.
      During fractionated irradiation C225 was given once per week. Experimental
      endpoints were tumour growth delay and local tumour control 120 after end of
      irradiation. RESULTS: C225 treatment resulted in prolongation of tumour growth
      delay after drug treatment alone as well as after single dose and fractionated
      irradiation. TCD50 values were reduced from 56.3 Gy [95% CI 50; 62 Gy] after
      single dose irradiation alone to 46.0 Gy [41;51] (enhancement ratio [ER]=1.22,
      P<0.01) after 1 C225 injection and 47.7 Gy [44; 51] after 4 injections of the
      drug (ER=1.18, P=0.06). After fractionated irradiation, tumour control dose 50%
      (TCD50) was 73.0 Gy [64; 82] in control tumours and 63.1 Gy [57; 69] after
      simultaneous C225 treatment, corresponding to an ER of 1.2 (P=0.01). CONCLUSION:
      Treatment of FaDu hSCC with the anti-EGFR mAb C225 resulted in a significant
      prolongation of tumour growth delay after single dose and fractionated
      irradiation. In contrast to previous results on the EGFR-TK inhibitor BIBX1382BS,
      this prolongation of growth delay translated into a slight but significant
      improvement of local tumour control. The data indicate that different classes of
      EGFR inhibitors may have different potential to improve the outcome of
      radiotherapy in the same tumour model.

PMID- 15734199
TI  - Radiosensitization of Ras-mutated human tumor cells in vitro by the specific EGF
      receptor antagonist BIBX1382BS.
AB  - BACKGROUND AND PURPOSE: To investigate the cellular and molecular consequences of
      antagonizing radiation-induced EGFR-activation in vitro. PATIENTS AND METHODS:
      The effect of the EGFR tyrosine kinase inhibitor BIBX1382BS on radiation
      sensitivity was determined after single- and fractionated-dose irradiation in
      human cell lines of bronchial carcinoma (A549), breast adeno-carcinoma (MDA-MB
      231), pharyngeal squamous-cell carcinoma (FaDu), squamous-cell carcinoma of
      cervix (HTB-35) as well as normal (HSF-7) and transformed (HH4-DED) human skin
      fibroblasts. Applying immuno-precipitation and western blotting pattern of
      radiation-dependent activation of different components of EGFR-signaling after
      pre-treatment with and without BIBX1382BS or other tyrosine kinase inhibitors was
      analyzed. RESULTS: Autophosphorylation of EGFR which occurred 1-5 min after
      irradiation (IR, 2 Gy) or treatment with EGF (100 ng/ml) could be inhibited in
      all cells tested by pre-treatment with BIBX1382BS for 30 min. Combination of drug
      treatment with fractionated irradiation (4x2 Gy) led to a strong radiosensitizing
      effect in Ras-mutated A549 and MDA-MB-231 cells, but not in normal Ras presenting
      cell lines FaDu and HTB-35 or normal and transformed human skin fibroblasts. Both
      BIBX1382BS as well as the PI3 kinase inhibitor LY294002 led to a blockage (for
      A549 cells) or reduction (for FaDu cells) of radiation-induced P-AKT. In contrast
      to FaDu cells, treatment of A549 cells with LY294002 resulted in a significant
      decrease of post-irradiation survival of A549 cells. Furthermore, only in Ras
      mutated cells, but not in normal Ras cells clonogenic survival and
      phosphorylation of AKT was sensitive to pre-treatment with TGF-alpha-neutralizing
      antibody indicating an important role of TGF-alpha in regulating radiation
      induced EGFR signaling. CONCLUSIONS: Enhancement of radiation sensitivity by the
      specific EGFR-tyrosine kinase inhibitor BIBX1382BS is not generally achieved in
      human tumor cells, but depends most likely on the Ras genotype of the cell lines
      tested.

PMID- 15734200
TI  - Does inverse planning applied to Iridium192 high dose rate prostate brachytherapy
      improve the optimization of the dose afforded by the Paris system?
AB  - BACKGROUND AND PURPOSE: The purpose of the work is to analyse for 192Ir prostate
      brachytherapy (BT) some of the different steps in optimizing the dose delivered
      to the CTV, urethra and rectum. MATERIALS AND METHODS: Between 07/1998 and
      12/2001, 166 patients were treated with 192Ir wires providing a low dose rate,
      according to the Paris system philosophy and with the 2D version of the treatment
      planning IsisR. 40-45 Gy were delivered after an external beam radiotherapy of 40
      Gy. The maximum tolerable doses for BT were 25 Gy to the anterior third of the
      rectum on the whole length of the implant (R dose) and 52 Gy to the urethra on a
      1cm length (Umax). A Umax/CTV dose ratio >1.3 represented a pejorative value as
      the planned dose of 40-45 Gy could not be achieved. On the other side a ratio
      <or=1.25 was considered optimal and the intermediate values satisfactory. A R/CTV
      dose ratio <0.55 which is easily obtained was also stated as an optimal
      situation. From the CT Scan images performed for these implants, a theoretical
      study investigated the possibilities of complementary optimization afforded by a
      3D treatment planning. This work was based on an inverse planning philosophy and
      a stepping source technology (SST) for high dose rate 192Ir sources. RESULTS: At
      the end of a learning curve reaching a plateau after the first 71 patients, 90%
      of the implants with 192Ir wires were stated at least satisfactory for a total
      rate of 82% for the whole population. When the 3D dosimetry for SST was used, the
      initial values >1.25 decreased significantly with optimization required on CTV
      contours and additional constraints on urethra while the R/CTV ratio was
      maintained under 0.55. For initial Umax/CTV >1.3 or >1.25 but <or=1.3 indeed, the
      mean respective values of 1.41+/-0.16 and 1.28+/-0.01 decreased to 1.28+/-0.24
      and 1.17+/-0.09 (P<0.001), allowing to increase the total dose to the CTV by 4
      Gy. CONCLUSIONS: The Paris system which assumes a homogeneous distribution of a
      minimum number of catheters inside the CTV allowed to anticipate a satisfactory
      dosimetry in 82% of cases. However, this precision rate could be improved until
      95% with an optimization approach based on an inverse planning philosophy. These
      new 3D optimization methods, ideally based on good quality implants at first
      allow to deliver the highest doses with minimal probability of creating cold
      spots inside the CTV or unacceptable hot spots outside.

PMID- 15734201
TI  - GEC/ESTRO-EAU recommendations on temporary brachytherapy using stepping sources
      for localised prostate cancer.
AB  - BACKGROUND AND PURPOSE: The aim of this paper is to present the GEC/ESTRO-EAU
      recommendations for template and transrectal ultrasound (TRUS) guided
      transperineal temporary interstitial prostate brachytherapy using a high dose
      rate iridium-192 stepping source and a remote afterloading technique. Experts in
      prostate brachytherapy developed these recommendations on behalf of the GEC/ESTRO
      and of the EAU. The paper has been approved by both GEC/ESTRO steering committee
      members and EAU committee members. PATIENTS AND METHODS: Interstitial
      brachytherapy (BT) to organ confined prostate cancer can be applied as a boost
      treatment in combination with external beam radiation therapy (EBRT) using a
      proper number of BT fractions in curative intent. Temporary transperineal BT
      alone or in combination with EBRT are feasible as a palliative/salvage treatment
      modality because of local recurrence, however, without large clinical experience.
      The use of temporary BT as a monotherapy is subject of ongoing clinical research.
      RESULTS: Recommendations for pre-treatment investigations, patient selection,
      equipment and facilities, the clinical team, the implant procedure (treatment
      planning and needle implantation) dose and fractionation, reporting, management
      of side effects and follow-up are given. CONCLUSIONS: These recommendations are
      intended to be technically and advisory in nature, but the ultimate
      responsibility for the medical decision rests with the treating physician.
      Although, this paper represents the consensus of an interdisciplinary group of
      experts, TRUS and template guided temporary transperineal interstitial implants
      in prostate cancer are a constantly evolving field and the recommendations are
      subject to modifications as new data become available.

PMID- 15734203
TI  - Long-term outcome of high dose rate brachytherapy in radiotherapy of localised
      prostate cancer.
AB  - BACKGROUND AND PURPOSE: High dose rate brachytherapy (HDR-BT) in prostate cancer
      (PC) is receiving increasing interest. The steep dose gradient gives a
      possibility to escalate the dose to the prostate. If the alpha/beta ratio is low
      for PC, hypofractionation will be of advantage. A retrospective analysis of
      outcome in patients (pts) consecutively treated with combined HDR-BT and
      conformal external beam radiotherapy (ERT) was performed. MATERIAL AND METHODS:
      Data from 214 pts treated consecutively from 1988 to 2000 were analysed. The
      median age was 64 years (50-77). Median follow up was 4 years (12-165 months).
      Pre-irradiatory endocrine therapy was given to 150 pts (70%). The pts were
      divided into low-, intermediate- and high (80/87/47 pts) risk groups according to
      the occurrence of none, one, or more risk factors defined by T-classification,
      PSA and histopathology. ERT was given with 2 Gy fractions to 50 Gy. HDR-BT
      consisted of two 10 Gy fractions. RESULTS: Overall 5-year biochemical no evidence
      of disease (bNED) was 82%, and for the low-, intermediate-, and high-risk group
      bNED was 92, 88 and 61%, respectively. PSA-relapse was found in 17, local
      recurrence in 3 and distant metastases in 13 pts. Five pts died of PC. No
      recurrences were observed after 5 years. Severe late complications were few.
      Urethral stricture (13 pts) was the most frequent. No severe rectal complications
      were seen. CONCLUSION: Dose escalation with HDR-BT is safe and effective in
      radiotherapy of localised PC.

PMID- 15734202
TI  - A dosimetric intercomparison of brachytherapy facilities in Ireland, Scotland and
      the North of England.
AB  - BACKGROUND AND PURPOSE: A dosimetric intercomparison of brachytherapy remote
      afterloading units in Ireland, Scotland and the North of England has been carried
      out involving 9 radiotherapy centres, and sampling 5 HDR and 6 LDR units.
      MATERIALS AND METHODS: Absolute calibrations have been performed in air on both
      HDR and LDR sources. The results are expressed in terms of a ratio of local to
      calibrated value. Frequency distributions were obtained for the multi-source LDR
      units by individually measuring each source. Using these distributions the effect
      of non-uniform source strength on the dose rate at Manchester point A was
      assessed for a typical clinical brachytherapy insertion for carcinoma of the
      cervix. Both frequency and dose rate distribution curves were modeled using
      normal statistics and characterised in terms of the mean (mu) and standard
      deviation (sigma). RESULTS: Evaluation of the HDR units indicated a mean ratio of
      1.008 (+/-0.01) while for LDR the mean ratio was 0.997 (+/-0.02). The LDR
      frequency distributions demonstrated a variation of sigma values extending from
      1.4 to 3.0% of mu. It was shown that this non-uniformity in source strength
      introduced an uncertainty in the treatment planning process of between 0.8 and
      1.8% when compared to the assumption of uniform source strength. CONCLUSIONS: The
      results of this intercomparison indicate dosimetric consistency between centres
      for both LDR and HDR units. The distribution of LDR source strengths were within
      expected limits and the resultant dose rate distributions were considered
      clinically acceptable.

PMID- 15734204
TI  - Limited efficacy of salvage radiotherapy for biopsy confirmed or clinically
      palpable local recurrence of prostate carcinoma after surgery.
AB  - BACKGROUND AND PURPOSE: To assess the efficacy of salvage radiotherapy (RT) for
      biopsy confirmed or clinically palpable local recurrence of prostate
      adenocarcinoma after radical prostatectomy (RP). PATIENTS AND METHODS: We
      retrospectively analyzed 44 patients treated with salvage RT for biopsy confirmed
      or clinically palpable local recurrence between 1991 and 2000. Thirty-six had
      positive biopsy for local recurrence and the rest without histological
      confirmation had clinically palpable disease. All had rising PSA at the time of
      RT (median: 3.7). Median interval from RP to RT was 2.6 years. Thirty-six
      received salvage RT alone, while eight had a short course (<4 months) of androgen
      ablation prior to RT. RT doses were 60-66Gy in 30-33 fractions. Freedom from PSA
      failure was defined as the maintenance of PSA<or=0.2. RESULTS: Median follow-ups
      from RP and salvage RT were 8.7 and 5.5 years, respectively. All but one achieved
      local control clinically. The actuarial PSA relapse-free and survival rate at 5
      years were 11 and 87%, respectively. On Cox regression analysis, significant
      predictors for relapse were PSA level prior to salvage RT, and Gleason score.
      CONCLUSIONS: The efficacy of salvage RT alone for local recurrence was limited.
      This study suggests a need to explore other strategies incorporating systemic
      therapy, and the importance of timely referral for consideration of salvage RT in
      patients with rising PSA after surgery.

PMID- 15734205
TI  - The design and testing of a solid phantom for the verification of a commercial 3D
      seed reconstruction algorithm.
AB  - BACKGROUND AND PURPOSE: To test the implementation of a new solid phantom and to
      study the accuracy and the reliability of 3D seed reconstruction algorithms in
      prostate seed implants. PATIENTS AND METHODS: A solid phantom, the Kiel-phantom,
      to simulate prostate implants was designed. Several measurements were performed
      with this phantom to test the three-film seed reconstruction using a commercial
      planning system. RESULTS: Precision of better than 0.1 mm (SD) were found for
      seed combinations when source projections do not overlap. If seeds overlapped
      from two or more gantry angles, the software showed serious miscomputations with
      seed displacements of more than 30.0mm. CONCLUSIONS: Systematic measurements were
      carried out which demonstrated that the solid phantom can be an advantageous tool
      to increase the quality assessment for seed planning systems.

PMID- 15734206
TI  - Strategies to reduce the systematic error due to tumor and rectum motion in
      radiotherapy of prostate cancer.
AB  - BACKGROUND AND PURPOSE: The goal of this work is to develop and evaluate
      strategies to reduce the uncertainty in the prostate position and rectum shape
      that arises in the preparation stage of the radiation treatment of prostate
      cancer. PATIENTS AND METHODS: Nineteen prostate cancer patients, who were treated
      with 3-dimensional conformal radiotherapy, received each a planning CT scan and 8
      13 repeat CT scans during the treatment period. We quantified prostate motion
      relative to the pelvic bone by first matching the repeat CT scans on the planning
      CT scan using the bony anatomy. Subsequently, each contoured prostate, including
      seminal vesicles, was matched on the prostate in the planning CT scan to obtain
      the translations and rotations. The variation in prostate position was determined
      in terms of the systematic, random and group mean error. We tested the
      performance of two correction strategies to reduce the systematic error due to
      prostate motion. The first strategy, the pre-treatment strategy, used only the
      initial rectum volume in the planning CT scan to adjust the angle of the prostate
      with respect to the left-right (LR) axis and the shape and position of the
      rectum. The second strategy, the adaptive strategy, used the data of repeat CT
      scans to improve the estimate of the prostate position and rectum shape during
      the treatment. RESULTS: The largest component of prostate motion was a rotation
      around the LR axis. The systematic error (1 SD) was 5.1 degrees and the random
      error was 3.6 degrees (1 SD). The average LR-axis rotation between the planning
      and the repeat CT scans correlated significantly with the rectum volume in the
      planning CT scan (r=0.86, P<0.0001). Correction of the rotational position on the
      basis of the planning rectum volume alone reduced the systematic error by 28%. A
      correction, based on the data of the planning CT scan and 4 repeat CT scans
      reduced the systematic error over the complete treatment period by a factor of 2.
      When the correction was carried out later in the treatment (based on the data of
      more scans) the overall reduction was less. For the rectum, the first strategy
      performed best at the upper anterior side, where a reduction of the anterior
      posterior displacement of 30% could be achieved. The systematic error could be
      reduced by 43% for the whole rectum by using the data of 4 repeat CT scans and
      the planning CT scan. CONCLUSIONS: Both the pre-treatment as well as the adaptive
      correction strategy reduced the systematic error in the prostate position and
      rectum position and shape. A smaller systematic error makes it possible to safely
      reduce the margin around the clinical tumor volume, so that normal tissues can be
      spared or the prescription dose can be escalated.

PMID- 15734207
TI  - Rectal and bladder motion during conformal radiotherapy after radical
      prostatectomy.
AB  - BACKGROUND AND PURPOSE: To investigate the extent and the impact of rectum and
      bladder motion during adjuvant conformal radiotherapy (3DCRT) after radical
      prostatectomy (RP). MATERIALS AND METHODS: Nine patients previously operated with
      RP and treated with early adjuvant 3DCRT were considered for this investigation.
      Weekly CT scans were collected during treatment (CT1-CTn, n=4-6) and were 3D
      matched using bony anatomy with the planning CT (CT0). A single observer drew the
      contours of rectum and bladder on all CTs. The CTV (prostate+/-seminal vesicles
      surgical bed) was contoured on CT0 by a single observer and a 4-field 3DCRT
      technique was planned: dose statistics/dose-volume histograms (DVH) of the rectum
      and bladder were calculated for each contour referred to CT0, CT1...CTn. Average
      DVHs during the treatment were then calculated and compared with the planned DVH.
      Cranial, caudal, anterior and posterior shifts of rectum and bladder were also
      assessed by lateral BEV projections. NTCP values for the rectum were also
      calculated using the Lyman-Kutcher model. RESULTS: Random variations of volume
      and DVHs due to variable filling content were found for the bladder; a trend of
      the bladder to be more empty during therapy with respect to CT0 was also found
      (median values: 45 cm3 vs. 79 cm3, P=0.02). Regarding the rectum, 6/9 patients
      showed an average DVH 'worse' than the planned one (up to 10-20%). BEV and volume
      analyses showed that the rectal volume decreased in 3/9 patients after the first
      week. In 6/9 patients a systematic anterior shift of the cranial half of the
      rectum was detected and found to be correlated with a corresponding shift of the
      posterior border of CTV contoured by five different observers. The average rectal
      NTCP during therapy was systematically higher than the NTCP referred to CT0
      (average increase 1.2%; range 0.0-3.7%, for a 70 Gy ICRU dose, P=0.01).
      CONCLUSIONS: The impact of systematic uncertainty due to rectal wall motion seems
      to be relatively high for patients treated with adjuvant 3DCRT after RP. The
      detected trend of the rectum in migrating anteriorly during therapy is consistent
      with post-surgery settlement effects and/or some modification of rectum mobility
      due to irradiation. Rectal motion (and consequent shifts of CTV) was large at the
      half cranial portion of the rectum while it was very small below the flexure.

PMID- 15734208
TI  - Dose-volume histograms associated to long-term colorectal functions in patients
      receiving pelvic radiotherapy.
AB  - BACKGROUND AND PURPOSE: To correlate long-term colorectal dysfunctions following
      radical radiotherapy for bladder or prostate cancer with clinical parameters and
      dose-volume histogram parameters of the small intestine, rectum, and anal canal
      volume. MATERIALS AND METHODS: Seventy-one patients previously treated for
      bladder or prostate cancer were interviewed following CT-based radiotherapy of 60
      70 Gy with questions concerning long-term colorectal dysfunctions. Median follow
      up time was 30 months (range 12-109 months). Clinical parameters and parameters
      from the dose-volume histograms were correlated with colorectal dysfunctions
      (Spearman's test). Median and quartile values of all parameters were used as cut
      off values for statistical analyses. A logistic regression model was used for
      analysis of urgency and incontinence in relation to median or maximum radiation
      dose to the anal canal volume. RESULTS: Rectum length, volume and several dose
      volume parameters from the anal canal volume and rectal volume were correlated
      with late organ dysfunctions. In a logistic model, fecal urgency and incontinence
      were dependent of dose-volume parameters from the anal canal volume. No relation
      between age or follow-up time and late effects were found. Dose-volume parameters
      of the small intestine were not related to any late dysfunctions. CONCLUSIONS: A
      relationship between several late anorectal dysfunctions and dose-volume
      parameters from the rectum and anal canal volume was demonstrated. It is
      recommended to exclude the anal canal volume from the high dose-volume and to
      apply rectal shielding whenever possible to prevent late anorectal dysfunctions.

PMID- 15734209
TI  - The effective dose (Deff) for electron beams.
AB  - BACKGROUND AND PURPOSE: Calculation of the effective dose and proposal of a dose
      specification method for the electron beams. PATIENTS AND METHODS: In a
      homogenous water phantom the 3D dose distributions for electron beams of energy
      6, 9, 12, 15, 18 and 21 MeV and beam size 10x10 cm were calculated. For a volume
      encompassed with 80, 85 and 90% isodose, the mean dose and the SD were calculated
      for each energy. Using the Brahme's formulae, the effective dose was calculated.
      RESULTS: The larger the minimum dose (value of the encompassing isodose), the
      larger the mean dose and the smaller the SD. The mean doses and SD to the volume
      encompassed with 80, 85 and 90% are in the range of 91-94%, and 5.1-6.2%, 93-96%
      and 4.2-4.6%, 94-96% and 3.0-3.2%, respectively. Thus the effective dose for the
      volume encompassed with 80, 85 and 90% are about 90, 93 and 95%, respectively.
      CONCLUSION: Taking into account the requirements regarding dose uniformity within
      the PTV and the sparing effect for normal tissue situated under the PTV, we
      propose to keep the 85% isodose as a minimum one and to prescribe the dose to the
      90% isodose. The present method may be applied for single electron beams and
      typical cases.

PMID- 15734210
TI  - Measurements and treatment planning calculations of electron dose distributions
      below bolus edges.
AB  - Electron dose distributions below bolus edges of various thicknesses and angles
      were measured using a diode in a water phantom. The measurements were compared
      with treatment planning calculations using the gamma method. Below 5 mm boluses,
      the dose variations were acceptable for all angles, while for boluses thicker
      than 5mm, the lowest edge gave the smallest dose variations. The calculated dose
      distributions agreed well with the measured dose distributions.

PMID- 15734211
TI  - Analysis of p16INK4A gene promoter in male germ-cell tumors: identification of a
      new point mutation.
AB  - Human male germ-cell tumors of seminoma type display aberrant expression of INK4
      family inhibitors of the cell cycle including CDKN2-encoded p16INK4A. The
      mechanisms underlying the altered p16INK4A expression are not fully understood.
      Indeed, neither genetic/epigenetic alterations in CDKN2 coding sequence nor its
      promoter hypermethylation could explain all anomalies. To assess whether the
      aberrant p16INK4A expression could be related to the alterations in CDKN2
      regulatory sequence, we screened seminoma DNAs from 19 patients for the promoter
      mutations. Combined polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and automated DNA-sequencing approaches indicated an
      adenine insertion at the position-1973 (relative to the ATG codon at+1) of CDKN2
      promoter in one particular patient. The immunohistochemical analysis pointed to
      the correlation between the observed promoter mutation and the loss of p16INK4A
      protein expression. These data suggest that in addition to previously
      characterized anomalies, the identified CDKN2 promoter mutation may be relevant
      for altered p16INK4A protein expressions in at least some seminoma.

PMID- 15734212
TI  - Osteoclast-like giant cell tumor in mucinous cystadenocarcinoma of the pancreas:
      an immunohistochemical and molecular analysis.
AB  - Osteoclast-like giant cell tumors (OLGT) are rare neoplasms of the pancreas and
      mostly associated with ductal adenocarcinomas. In this report, we present the
      rare case of OLGT associated with mucinous cystadenocarcinoma (MCC). We
      investigated the expression profile of both tumors by methods of molecular
      biology and immunohistochemistry. The panel of markers included osteopontin,
      her2/neu, mismatch repair genes, K-ras, p53, E-cadherin, VEGF-C, and podoplanin.
      Osteopontin was expressed by the osteoclast-like giant cells but not by the
      mononuclear tumor cells of the OLGT. We detected an amplification and
      overexpression of her2/neu in the MCC but not in the OLGT. Although we observed
      an immunohistochemical expression of hMSH2 and hMLH1 in the OLGT, we were not
      able to confirm this result by western blot analysis. We also did not find any
      microsatellite instability (D2S123, BAT26). While mutation of K-ras codon 12 was
      found in both tumor components, there was wild-type DNA of p53. E-cadherin was
      expressed in MCC but not in OLGT. VEGF-C was only positive in osteoclast-like
      giant cells and some of the mononuclear cells of OLGT. The vessel-rich stroma of
      OLGT did not present any podoplanin-positive lymphatic vessel. The observation of
      our case and others in the published literature may indicate separating OLGT with
      undifferentiated carcinoma from OLGT with MCC for the better clinical outcome of
      the latter.

PMID- 15734213
TI  - Cigarette smoking and cancer incidence risk in adult men: National Health
      Insurance Corporation Study.
AB  - We analyzed risk while adjusting for age, body mass index, frequency of moderate
      physical activity, alcohol consumption, preference for vegetables versus meats,
      and frequency of meat consumption in a multivariate analysis and based our
      findings on not mortality data but incidence data. 733,134 Korean men who were 30
      years old or older, insured by the National Health Insurance Corporation, and had
      a medical evaluation in 1996 were included in the study and followed up through
      2000. During the 4-year follow-up period of 3,590,872 person-years, we identified
      7204 new cases. We used the Cox proportional hazards model to estimate adjusted
      relative risks (aRRs), 95% confidence intervals (CIs). The association of current
      cigarette smoking was significantly stronger as compared with never smokers; aRR
      was 1.49 (95% CI=1.39-1.59) for all cancers, 4.46 (2.32-8.57) for esophageal,
      3.83 (2.97-4.94) for lung, 3.01 (1.58-5.72) for laryngeal, 2.24 (1.48-3.39) for
      urinary bladder, 1.62 (1.42-1.84) for gastric, 1.75 (1.12-2.74) for oral and
      pharyngeal, 1.58 (0.97-2.27) for pancreatic, and 1.50 (1.29-1.74) for liver
      cancer. Our findings, based on incidence data, confirmed that differences in
      smoking habit were responsible for most of the differences observed in smoking
      related cancers.

PMID- 15734214
TI  - The associations between psychological distress and cancer prevention practices.
AB  - The aim of the current study was to determine the extent to which psychological
      distress is associated with cancer prevention practices among otherwise healthy
      adults in the community (N=30,223). Using data from the 2000 National Health
      Interview Survey, a series of multiple logistic regression analyses were used to
      estimate the associations between psychological distress and selected cancer
      prevention practices. Results indicate that psychological distress was directly
      associated with an increased likelihood of daily cigarette smoking, physical
      inactivity, and obesity. Only smoking status mediated the relation between
      psychological distress and perceived cancer risk. Individuals who reported higher
      psychological distress were more likely to engage in specific cancer screenings
      before reaching the recommended age. This effect was partially mediated by
      perceived cancer risk. The higher levels of cigarette smoking and physical
      inactivity among psychologically distressed adults support the need for
      integration of cancer prevention and mental health interventions to reduce
      specific cancer risk in high-risk adults. Further research is needed to
      differentiate the causal pathways and mechanisms linking heightened individual
      cancer risk, potentially comorbid mental disorders or psychological conditions,
      and cancer screening adherence.

PMID- 15734215
TI  - The relative distribution of oncogenic types of human papillomavirus in benign,
      pre-malignant and malignant cervical biopsies. A study with human papillomavirus
      deoxyribonucleic acid sequence analysis.
AB  - The aim of the present investigation was to define the spectrum of oncogenic
      types of human papillomavirus (HPV) present in benign, pre-malignant (low-grade
      and high-grade squamous intraepithelial lesions, LSIL and HSIL) and malignant
      cervical lesions. The study comprises 215 HPV-positive biopsies, analysed with
      PCR, followed by sequence analyses of the HPV DNA. Fifeteen oncogenic types of
      HPV were identified. In 170 benign or pre-maligant alterations, the most common
      being HPV 16 (51%), HPV 31 (8%), HPV 18 (7%) and HPV 45 (6%). HPV 33, 35, 51, 56,
      58, 66, and 70 occurred in about 1-4%. The prevalence of HPV 39, 52, 56, 59 and
      73 was <1%. All the observed types of HPV, except 39 and 52, occurred in SIL
      lesions. The most common oncogenic HPV types (16 and 18), occurring in 45
      invasive squamous carcinomas, comprised 76 per cent of the tumours, whereas less
      frequent HPV types (31, 33, 52, 56, 67, 70 and 73) were each found in about 2-4%.
      Double HPV infections were not observed. In conclusion, a total of 15 different
      oncogenic HPV types were identified, of which 13 types were present in pre
      malignant cervical lesions and 9 in malignant lesions. This information may have
      some relevance when HPV analyses are considered as an adjunct to the organised
      screening of cervical cancer and for those working with the development of HPV
      vaccines for the prevention of cervical cancer.

PMID- 15734217
TI  - The role of folates in squamous cell carcinoma of the head and neck.
AB  - The primary objective of this review is to explore the hypothesis that folate
      insufficiency may be important in the pathogenesis of squamous cell carcinomas of
      the head and neck (SCCHN) and that folate repletion may be an effective component
      of chemoprevention. The main results are that folate insufficiency disrupts DNA
      global and specific gene methylation patterns such that the activity of certain
      tumor suppressor genes such as p16 and possibly p53 may be lost. Folate pool
      imbalance and impaired repair mechanisms may contribute to DNA instability and
      strand breaks. Sensitive methods exist for identification of individuals with
      folate insufficiency in contrast to the relatively insensitive conventional serum
      or red cell folate assays with broad "normal" ranges. The impact of folate
      supplementation can thus be quantified. Folate imbalance may result from
      alterations in folate cellular uptake by the reduced folate carrier (RFC) and/or
      the folate receptor (FR) and polymorphisms in enzymes important in folate
      retention such as folylpolyglutamate synthetase and in folate modification such
      as methylene tetrahydrofolate reductase (MTHFR). Known predisposing factors for
      SCCHN such as alcohol and tobacco carcinogens may influence folate balance.
      Folate supplementation may reduce primary or secondary risk of cancer. Formal
      studies of folate sufficiency in persons at risk for or diagnosed and treated for
      SCCHN are needed to define the role of folate supplementation in the prevention
      of these cancers.

PMID- 15734216
TI  - NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic
      lesions and oral squamous cell carcinoma.
AB  - Previous investigations in our laboratory and others (Chen et al., 1998) have
      shown that the levels of certain inflammatory, proangiogenic cytokines in saliva
      and tissue specimens of patients with oral premalignant lesions (OPML) are
      elevated. We have also shown that these cytokines are elevated in tissue culture
      of oral squamous cell carcinoma (OSCC) cell lines. The purpose of this pilot
      study was to determine the level of several inflammatory, NF-kappaB-dependent
      cytokines in whole unstimulated saliva (WUS), in subjects with OPML as compared
      to those with diagnosed OSCC. Subjects (n=13) with OMPL, OSCC (n=13), and age-sex
      matched controls without oral lesions (C) (n=13) were enrolled. The mean age was
      58.7 years. WUS was collected by standard techniques for 5 min (Navazesh, 1993).
      WUS samples were centrifuged and the cytokine analysis was performed on the
      supernatants by ELISA as previously described by Ondrey et al. (1991). The
      cytokines analyzed were: TNF-alpha, interleukin-1, interleukin-6, and interleukin
      8 (TNF-alpha, IL-1, IL-6, and IL-8). The results as analyzed by Pairwise t-tests
      revealed significant differences in the salivary levels of: (1) TNF-alpha:
      (mean+/-S.E.M.: TNF-alpha-OSSC=28.9+/-14.6* pcg/ml versus OPML=10.5+/-7.4* pcg/ml
      versus controls=3.0+/-1.0 pcg/ml; *p<0.01); (2) IL-1: (IL-1-OSSC=454.4+/-215.8*
      pcg/ml versus OPML=255.1+/-124.8* pcg/ml versus controls=173.2+/-66.9 pcg/ml;
      *p<0.01); (3) IL-6: (mean+/-S.E.M.: IL-6-OSSC=88.2+/-43.2* pcg/ml versus
      OPML=70.8+/-24.3* pcg/ml versus controls=1.4+/-1.0 pcg/ml; *p<0.001) and (4) IL-8
      in saliva: (mean+/-S.E.M.: IL-8-OSSC=3154.1+/-1023.2* pcg/ml versus OPML=1918.2+/
      899.1* pcg/ml versus controls=1580.7+/-789.0 pcg/ml; *p<0.001). There was a
      significant increase in the levels of all cytokines in the saliva of the OPML as
      compared to controls, and a significant difference in the cytokines of OSSC
      saliva compared to the OPML and controls. These results suggest that these
      proangiogenic, proinflammatory cytokines are elevated in the saliva of patients
      with OSSC and OPML as compared to controls, which may have diagnostic and/or
      prognostic significance.

PMID- 15734218
TI  - Comparison of chemopreventive effects of Vitamin E plus selenium versus melatonin
      in 7,12-dimethylbenz(a)anthracene-induced mouse brain damage.
AB  - In this work, the protective effect of Vitamin E plus selenium (Vit E+Se) and
      melatonin against 7,12-dimethylbenz(a)anthracene (7,12-DMBA)-induced changes in
      superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT) and
      carbonic anhydrase (CA) activities and malonedialdehyde (MDA) levels of mouse
      brain were compared. 12-month old mice were divided into four groups each
      including 10 animals. The first group served as control group. The second group
      was treated with 7,12-DMBA (20 mg/(kg day)). The third group was treated with
      7,12-DMBA and Vitamin E (90 microg/(individual day)) and selenium (1.8
      microg/(individual day)) simultaneously. The fourth group was treated with 7,12
      DMBA and melatonin (4.2 mg/(kg day)) simultaneously. Treatment continued for 21
      days after which the mice were sacrificed and brain homogenates were prepared.
      7,12-DMBA treated group exhibited significantly decreased levels of brain SOD,
      GSHPx, CAT and CA activities and increased MDA levels as compared to control.
      Vitamin E+Se fully or partially restored enzyme inhibition except for SOD. Lipid
      peroxidation was also reduced in Vitamin E+Se treated group. Melatonin provided a
      better protection for SOD, GSHPx and CAT, and a plausible protection for CA
      activity. Protection against lipid peroxidation measured as MDA in melatonin
      treated group was appreciable although slightly lesser than the protection
      provided by Vitamin E+Se. The results imply that Vitamin E+Se and melatonin both
      provide chemoprevention against 7,12-DMBA-induced oxidative stress in mouse
      brain.

PMID- 15734219
TI  - Spectra of antinuclear antibodies in patients with squamous cell carcinoma of the
      lung and of the head and neck.
AB  - Squamous cell carcinoma of the head and neck (HNSCC) and of the lung (LSCC) share
      some important risk factors, but differ substantially in terms of prognosis and
      treatment. A pulmonary nodule developing in patients with surgically cured HNSCC
      may pose a diagnostic dilemma. Markers able to distinguish these two common
      malignancies would be of major clinical importance. In this work we compared the
      spectrum of antinuclear antibodies (ANA) from 22 patients with SCCL to that of 40
      patients with HNSCC. Patient sera were used to probe immunoblots of nuclear
      extracts from all four major lung cancer cell types, normal lung fibroblasts,
      cells cultured from a HNSCC, and keratinocytes cultured from the field
      cancerization. The ability to classify retrospectively LSCC from HNSCC based on
      serum ANA reactivities was determined by recursive partitioning analyses. We
      found that while both malignancies share reactivities to a small group of nuclear
      antigens, other reactivities are directed against proteins uniquely or
      preferentially expressed in either SCCL or in SCCHN cells. Our work shows that
      autoimmunity is a prominent feature of squamous cell carcinoma and suggests that
      molecular characterization of nuclear antigens recognized by ANAs may lead to the
      discovery of markers valuable to distinguish LSCC from HNSCC.

PMID- 15734220
TI  - Negative correlation between poly-ADP-ribosylation of spleen cell histone
      proteins and initial duration of dimethylnitrosamine exposure to mice in vivo
      measured by Western blot immunoprobe assay: a possible biomarker for cancer
      detection.
AB  - Improved cancer detection involving suitable biomarkers with easy applicability
      is a challenge to our fight against cancer. Poly-ADP-ribosylation (PAR) of
      proteins is a likely candidate biomarker for this purpose because it meets the
      criterion well. This report is a step towards testing suitability of PAR as a
      biomarker for cancer detection. Swiss albino mice were exposed to
      hepatocarcinogen, dimethylnitrosamine (DMN), at a chronic dose, which is known to
      induce carcinogenesis in liver. PAR was monitored by a Western blot immunoprobe
      assay in spleen, a lymphoid organ, to find a correlation between PAR of spleen
      histone proteins and duration of DMN exposure. A negative, non-linear correlation
      was found for most histone proteins. The inhibition of PAR of histones was
      significant from 4 weeks onwards until the end of the observation. The inhibition
      was potentiated when 3-aminobenzamide was simultaneously administered. The
      results open up the possibility of PAR of cellular proteins being used as
      biomarker for cancer detection.

PMID- 15734221
TI  - Assessing missing data assumptions in longitudinal studies: an example using a
      smoking cessation trial.
AB  - Due to the chaotic nature of the clinical disorder, longitudinal data analysis in
      substance abuse research is plagued by missing values. To obtain an unbiased
      estimation on intervention effects, different longitudinal modeling strategies
      require various assumptions on the patterns and mechanisms of missing data. By
      defining missingness as intermittent missingness (occasional omission) and
      dropout (premature withdrawal), this article demonstrates statistical ways for
      assessing missing data assumptions using evidence from a clinical trial. Within
      the framework of multiple imputation, intermittent missing data are imputed first
      so that dropouts can be isolated and treated specifically. A computational tool
      called "pattern reduction resampling" is proposed to simplify missing data
      methods when the number of intra-subject repeated measures is large. To test
      whether missingness patterns are nondifferential across treatment conditions, a
      formal testing approach treats indicators of missingness as a special type of
      repeated measures (e.g., 0: intermittent missing, 1: observed, and 2: dropout
      missing). After reviewing the idea of ignorability for missing data and of
      classifying missingness mechanisms into subcategories, the article provides an
      example for assessing common assumptions on missingness mechanisms and how these
      assumptions affect model selection for significance testing. A carbon monoxide
      longitudinal data set in a smoking cessation study is used for illustration.

PMID- 15734222
TI  - Prevalence and correlates of crack-cocaine injection among young injection drug
      users in the United States, 1997-1999.
AB  - OBJECTIVES: We estimated prevalence and identified correlates of crack-cocaine
      injection among young injection drug users in the United States. METHODS: We
      analyzed data from the second Collaborative Injection Drug Users Study (CIDUS
      II), a 1997-1999 cohort study of 18-30-year-old, street-recruited injection drug
      users from six US cities. RESULTS: Crack-cocaine injection was reported by 329
      (15%) of 2198 participants. Prevalence varied considerably by site (range, 1.5
      28.0%). No participants injected only crack-cocaine. At four sites where crack
      cocaine injection prevalence was greater than 10%, recent (past 6 months) crack
      cocaine injection was correlated with recent daily injection and sharing of
      syringes, equipment, and drug solution. Lifetime crack-cocaine injection was
      correlated with using shooting galleries, initiating others into drug injection,
      and having serologic evidence of hepatitis B virus and hepatitis C virus
      infection. CONCLUSIONS: Crack-cocaine injection may be a marker for high-risk
      behaviors that can be used to direct efforts to prevent HIV and other blood-borne
      viral infections.

PMID- 15734223
TI  - Multidimensional assessment of nicotine dependence in adolescents.
AB  - Despite the critical importance of adolescent smoking, the assessment of nicotine
      dependence during this developmental period has been the subject of relatively
      little research. In this study, 301 adolescents (ages 12 through 18 years)
      reporting daily smoking were recruited for a project on alcohol use disorders
      (AUDs). The sample included 140 females and 161 males, 251 subjects from clinical
      and 50 from community sources, and 176 subjects with AUDs at the baseline
      assessment. Subjects were evaluated with the Nicotine Dependence Syndrome Scale
      (NDSS), the Fagerstrom Test for Nicotine Dependence (FTND) and a determination of
      average number of cigarettes per day (cigarettes/day). A varimax factor analysis
      of 27 NDSS items revealed four factors: (1) Drive/Tolerance (13 items; Cronbach
      alpha = 0.91); (2) Continuity (five items; Cronbach alpha = 0.67); (3) Priority
      (three items; Cronbach alpha = 0.64); (4) Stereotypy (five items; Cronbach alpha
      = 0.66). The NDSS total score, refined by the removal of four items, was also
      examined (23 items; Cronbach alpha = 0.90). Predicting cigarettes/day at follow
      up, initial smoking rate was the best predictor, with the FTND and NDSS Total
      score showing significant and similar predictive validity. The NDSS Total showed
      incremental validity in the prediction of smoking progression in a model
      including demographic characteristics, initial smoking rate and FTND. The
      findings suggest that the NDSS has acceptable psychometric properties when
      applied to adolescents, complementing smoking rate and FTND in a multidimensional
      smoking assessment.

PMID- 15734224
TI  - Post-traumatic stress disorder among people with heroin dependence in the
      Australian treatment outcome study (ATOS): prevalence and correlates.
AB  - This study documents the prevalence and correlates of post-traumatic stress
      disorder (PTSD) among Australian individuals with heroin dependence. Data was
      obtained from a cohort of 615 people dependent on heroin, 535 entering treatment
      for their heroin dependence and 80 individuals not in treatment. Trauma exposure
      (92%) and lifetime PTSD (41%) were highly prevalent. PTSD was prevalent across
      all treatment modalities, most commonly residential rehabilitation (52%) followed
      by maintenance therapies (42%), and detoxification (37%). The lowest prevalence
      was reported among those not in treatment (30%). Although men and women were
      equally likely to have experienced trauma (93% vs. 89%), women were more likely
      to develop lifetime PTSD (61% vs. 37%). For the large majority of those with
      PTSD, the condition was chronic (84%), with symptoms continuing for an average of
      9.5 years. Those with PTSD had more extensive polydrug use histories, poorer
      general physical and mental health, and more extensive health service
      utilisation. It is concluded that PTSD is highly prevalent among individuals with
      heroin dependence, presenting a significant challenge to treatment providers.

PMID- 15734225
TI  - Co-morbid post-traumatic stress disorder in a substance misusing clinical
      population.
AB  - BACKGROUND: USA studies have reported high rates of co-morbid post-traumatic
      stress disorder (PTSD) and substance (drugs and alcohol) dependence/misuse.
      Avoidance of trauma reminders and associated distress may be achieved by the use
      of drugs and alcohol, alternatively a substance abusing lifestyle might
      predispose such individuals to experience traumatic events. This may have
      implications for treatment and management of patients with co-morbid substance
      misuse and PTSD. There have been no British studies looking at the extent of
      traumatic life events and post-traumatic stress disorder amongst substance
      misusers, although high rates of reported sexual and physical abuse have been
      reported in two recent UK studies with drug- and alcohol-dependent patients in
      clinical settings. AIMS: (i) To investigate the prevalence of co-morbid PTSD in a
      UK substance use disorder (SUD) inpatient clinical population; (ii) to identify
      the characteristics, severity and types of trauma experienced; (iii) to compare
      SUD patients with and without co-morbid PTSD on substance use and history,
      psychological/psychiatric and social variables METHOD: This is a cross-sectional
      study involving interviews with patients and case note review. SUD inpatients
      were interviewed about traumatic experiences, PTSD, and addiction. RESULTS:
      Ninety-four percentage reported experiencing one or more PTSD criterion A
      traumatic experiences. 38.5% met criteria for current PTSD and 51.9% for lifetime
      PTSD. Significant differences between the PTSD and non-PTSD groups were found in
      PTSD and trauma-related variables, notably social variables and distress
      associated with traumatic experiences, but few differences were found in
      addiction severity (medical and psychiatric composite scores of the ASI) and
      psychiatric symptomatology. CONCLUSIONS: This study highlights not only the
      importance of assessment of trauma and PTSD amongst substance misusers but,
      conversely the need for the assessment of substance abuse among victims of PTSD.
      Co-morbid psychopathology is common, so trauma histories and PTSD symptoms may
      become embedded in other co-morbid psychopathology.

PMID- 15734226
TI  - A comparison of the content-, construct- and predictive validity of the cigarette
      dependence scale and the Fagerstrom test for nicotine dependence.
AB  - BACKGROUND: Research showed that the widely used Fagerstrom test for nicotine
      dependence (FTND) does not cover important aspects of dependence. A new test, the
      cigarette dependence scale (CDS-12), covers the main elements in DSM-IV and ICD
      10 definitions of dependence. We compared the psychometrics of CDS-12, FTND, and
      CDS-5 and the heaviness of smoking index (HSI), which are short versions of CDS
      12 and FTND, respectively. METHODS: Internet survey in 2002-2003. Participants
      were invited one month after answering the first survey to answer a second survey
      on smoking status and withdrawal symptoms. RESULTS: Eight hundred two smokers
      answered both surveys. Cronbach's alpha coefficients were higher for CDS-12
      (0.91) and CDS-5 (0.77) than for FTND (0.68) and HSI (0.63). Among 231 smokers
      who quit smoking at follow-up, higher baseline CDS-12 scores predicted higher
      withdrawal ratings at follow-up, for all withdrawal symptoms except appetite.
      FTND and HSI predicted higher craving in quitters, but did not predict the
      intensity of other withdrawal symptoms. Neither CDS-5, FTND or HSI predicted
      smoking cessation, but higher CDS-12 scores marginally predicted smoking
      cessation at follow-up (area under the receiver operating characteristic (ROC)
      curve = 0.55, 95% confidence interval = 0.51-0.59). CONCLUSIONS: CDS-12 had
      better content validity and internal consistency than FTND and was a slightly
      better predictor of withdrawal symptoms. Unexpectedly, higher (not lower) CDS-12
      scores predicted subsequent smoking cessation, perhaps because endorsement of
      some CDS-12 items implies accepting that one is dependent, which in turn could
      reflect motivation to quit. CDS-12 may represent an alternative to FTND for
      measuring cigarette dependence.

PMID- 15734227
TI  - Estimating drug treatment needs among state prison inmates.
AB  - Growing prison populations in the U.S. are largely due to drug-related crime and
      drug abuse. Yet, relatively few inmates receive treatment, existing interventions
      tend to be short-term or non-clinical, and better methods are needed to match
      drug-involved inmates to level of care. Using data from the 1997 Survey of
      Inmates in State Correctional Facilities, a nationally representative sample of
      14,285 inmates from 275 state prisons, we present a framework for estimating
      their levels of treatment need. The framework is drawn partly from the American
      Society of Addiction Medicine Patient Placement Criteria and other client
      matching protocols, incorporating drug use severity, drug-related behavioral
      consequences, and other social and health problems. The results indicate high
      levels of drug involvement, but considerable variation in severity/recency of use
      and health and social consequences. We estimate that one-third of male and half
      of female inmates need residential treatment, but that half of male and one-third
      of female inmates may need no treatment or short-term interventions. Treatment
      capacity in state prisons is quite inadequate relative to need, and improvements
      in assessment, treatment matching, and inmate incentives are needed to conserve
      scarce treatment resources and facilitate inmate access to different levels of
      care.

PMID- 15734228
TI  - Regular use of alcohol and tobacco in India and its association with age, gender,
      and poverty.
AB  - This study provides national estimates of regular tobacco and alcohol use in
      India and their associations with gender, age, and economic group obtained from a
      representative survey of 471,143 people over the age of 10 years in 1995-96, the
      National Sample Survey. The national prevalence of regular use of smoking tobacco
      is estimated to be 16.2%, chewing tobacco 14.0%, and alcohol 4.5%. Men were 25.5
      times more likely than women to report regular smoking, 3.7 times more likely to
      regularly chew tobacco, and 9.7 times more likely to regularly use alcohol.
      Respondents belonging to scheduled castes and tribes (recognized disadvantaged
      groups) were significantly more likely to report regular use of alcohol as well
      as smoking and chewing tobacco. People from rural areas had higher rates compared
      to urban dwellers, as did those with no formal education. Individuals with
      incomes below the poverty line had higher relative odds of use of chewing tobacco
      and alcohol compared to those above the poverty line. The regular use of both
      tobacco and alcohol also increased significantly with each diminishing income
      quintile. Comparisons are made between these results and those found in the
      United States and elsewhere, highlighting the need to address control of these
      substances on the public health agenda.

PMID- 15734229
TI  - Dopamine receptor regulation of ethanol intake and extracellular dopamine levels
      in the ventral pallidum of alcohol preferring (P) rats.
AB  - Sufficient evidence exists for the inclusion of the ventral pallidum (VP) into
      the category of a dopaminoceptive brain region. The effects of inhibiting
      dopamine D(1)- or D(2)-like receptors in the VP on (a) ethanol intake and (b)
      extracellular levels of dopamine, were investigated in the alcohol-preferring (P)
      rat. The D(1)-like antagonist, SCH-23390, and the D(2)-like antagonist, sulpiride
      (0.25-2 microg/0.5 microl) were bilaterally injected into the VP and ethanol
      (15%, v/v) intake was assessed in a 1 h limited access paradigm. The results
      indicate that microinjections of sulpiride significantly increased ethanol
      consumption (65% increase at the 2.0 microg dose). Whereas the D(1) antagonists
      SCH-23390 tended to decrease ethanol intake, the effect was not statistically
      significant. In a separate group of rats, reverse microdialysis of sulpiride and
      SCH-23390 (10-200 microM) were conducted in the VP of P rats. Local perfusion of
      only the 200 microM sulpiride dose significantly increased the extracellular
      levels of dopamine (maximal increase: 250% of baseline). On the other hand, local
      perfusion of SCH-23390 (10-200 microM) dose dependently increased the
      extracellular levels of dopamine 180-640% of baseline. Overall, the results of
      this study suggest that (a) tonic activation of D(2) postsynaptic receptors in VP
      imposes a limit on ethanol intake in the P rat; (b) there are few D(2)
      autoreceptors functioning in the VP; (c) there is tonic D(1)-like receptor
      mediated inhibitory feedback regulation of VP-dopamine release.

PMID- 15734230
TI  - Circumstances surrounding the first injection experience and their association
      with future syringe sharing behaviors in young urban injection drug users.
AB  - Young injection drug users are at heightened risk for acquisition of blood-borne
      infections because of their high rates of unsafe injection behaviors, yet there
      has been little research examining the circumstances surrounding injection drug
      users' first injection experience ('hit'). We examined the relationship between
      factors associated with young drug users' first hit and their future syringe
      sharing behaviors among 420 new initiates to injection drug use (less than 5
      years), aged 15-30 years old in urban Baltimore, Maryland. Contingency table
      analysis and logistic regression were used to determine the association between
      circumstances surrounding the first hit and recent receptive syringe sharing.
      Participants were primarily male (58.8%), White (71.2%), and were a median age of
      24 years (interquartile range [IQR]: 21-27 years). Adjusting for race, gender,
      and homelessness, the following variables were independently associated with
      recent receptive syringe sharing: age at first hit (adjusted odds ratio [AOR] =
      0.92 per year increase; 95% confidence interval [CI]: 0.87-0.98), self-injection
      at initiation (AOR = 0.55; 95% CI: 0.32-0.97) and using a syringe that had
      previously been used by someone else at first hit (AOR = 2.81; 95% CI: 1.70
      4.64). These data suggest that injection-related risk behaviors may be
      established as early as the onset of injection initiation, supporting the need to
      educate non-injectors of the harms associated with unsafe injection practices.

PMID- 15734231
TI  - Nicotine lozenge efficacy in light smokers.
AB  - BACKGROUND: Nicotine replacement therapy (NRT) has been proven to be effective in
      heterogeneous groups of smokers. However, analyses have not specifically examined
      efficacy among light smokers (< or =15 cigarettes per day). The objective of this
      study is to assess the efficacy of a nicotine lozenge in light smokers. METHODS:
      We conducted a secondary analysis of a randomized, placebo-controlled clinical
      trial contrasting active 2mg nicotine lozenge with placebo, and contrasting light
      smokers (< or =15 cigarettes per day) with moderate-heavy smokers (>15 cigarettes
      per day). Participants were 917 smokers who smoked their first cigarette >30 min
      after waking, and were randomized to active (n = 459) or placebo (n = 458)
      lozenge. Biochemically verified continuous abstinence was measured at 6 weeks and
      1 year. RESULTS: Nicotine lozenge significantly increased quit rates relative to
      placebo at 6 weeks (45.7% versus 31.1%; OR = 1.9 [1.3-2.8]) and at 1 year (19.2%
      versus 10.0%; OR = 2.3 [1.3-4.0]) among light smokers. Efficacy among light
      smokers did not differ from that among heavier smokers (ps>0.50). CONCLUSION: The
      nicotine lozenge is effective for light smokers.

PMID- 15734232
TI  - Gliding resistance of the extensor pollicis brevis tendon and abductor pollicis
      longus tendon within the first dorsal compartment in fixed wrist positions.
AB  - PURPOSE: While the etiology of de Quervain's disease is unknown, repetitive
      motion coupled with awkward wrist position and septation within the first dorsal
      compartment are considered causative factors. We hypothesize that these
      conditions might produce high gliding resistance, which could then induce micro
      damage of the tendons and retinaculum. The purpose of this study was to measure
      the gliding resistance of the extensor pollicis brevis and abductor pollicis
      longus tendons within the first dorsal compartment in a human cadaver model.
      METHODS: Fifteen human cadaver wrists, which included eight septation and seven
      non-septation wrists in the first dorsal compartment, were used. Gliding
      resistance of the extensor pollicis brevis and abductor pollicis longus tendons
      was measured in seven wrist positions: 60 degrees extension, 30 degrees
      extension, 0 degrees, 30 degrees flexion, 60 degrees flexion in neutral deviation
      and 30 degrees ulnar deviation, 15 degrees radial deviation in neutral
      extension/flexion. RESULTS: The overall gliding resistance was not different
      between septation and non-septation wrists (0.21 versus 0.19 N for abductor
      pollicis longus and 0.21 versus 0.15 N for extensor pollicis brevis,
      respectively), but there was a significant effect on gliding resistance due to
      wrist position (p<0.05) in both tendons. Interaction between wrist position and
      septation status was observed in the extensor pollicis brevis tendon (p<0.05).
      With septation, the gliding resistance of the extensor pollicis brevis was
      significantly higher in 60 degrees wrist flexion (0.51 N) compared to all other
      wrist positions tested (all less than 0.26 N) (p<0.05). In the non-septation
      group, gliding resistance was significantly higher in 60 degrees flexion (0.20 N)
      and 60 degrees extension (0.22 N) compared to the other five wrist positions (all
      less than 0.15 N) (p<0.05). Although no significant difference was observed, the
      extensor pollicis brevis tendon with septation tended to have higher gliding
      resistance than that without septation in wrist flexion. In 60 degrees of wrist
      flexion the abductor pollicis longus tendon had significantly higher gliding
      resistance (0.33 N) than the other wrist positions (all less than 0.26 N)
      (p<0.05). CONCLUSIONS: A combination of septation and wrist position
      significantly affected extensor pollicis brevis tendon gliding resistance in this
      cadaver model. These factors may contribute to the development of de Quervain's
      disease.

PMID- 15734233
TI  - Effect of elbow position on canine flexor digitorum profundus tendon tension.
AB  - Tendon injury in the finger remains a clinical challenge to hand surgeons. A
      canine model is commonly used to study biological effects of tendon injuries and
      their treatment. There is an important anatomical difference between human and
      canine anatomy that may be overlooked, however, namely that most of the flexor
      digitorum profundus (FDP) muscle in dogs takes its origin from the medial
      epicondyle of the humerus, whereas in humans this muscle arises purely from the
      forearm. Therefore, elbow position can affect the tension of this muscle in dogs,
      while having no effect in humans. The purpose of this study was to measure the
      effect of elbow position on tendon tension in the canine digit in vitro. Elbow
      position had a significant effect on tendon tension. Digit motion with the elbow
      fully flexed resulted in significantly higher tendon tension compared to digit
      motion with the elbow flexed 90 degrees or fully extended, regardless of digit or
      wrist position (p<0.05). The tension with the elbow flexed 90 degrees was also
      significantly higher than with the elbow fully extended (p<0.05). The maximum
      tendon tension with the elbow fully flexed was more than eight times larger than
      that of the fully extended elbow (p<0.05). We conclude that, in the canine model,
      elbow position is an important parameter that affects the passive tension applied
      to the flexor digitorum profundus, and, by implication, to any repair of that
      tendon. Dog flexor tendon rehabilitation protocols should therefore specify elbow
      position, in addition to wrist and digit position.

PMID- 15734234
TI  - Asymmetric atrophy of the supraspinatus muscle following tendon tear.
AB  - Muscle atrophy is a known consequence of muscle disuse, muscle denervation and
      tendon tear. Whereas after nerve injury muscle atrophies in the denervated area,
      the distribution of muscle atrophy following tear of its tendon is not known.
      Standardized MRI scans of 64 consecutive, painful shoulders were evaluated for
      supraspinatus tendon tearing, myotendinous retraction, supraspinatus muscle
      atrophy, fatty infiltration, ratio of the scapular (deep) and fascial
      (superficial) muscle area ("symmetry") and position of the central tendon within
      the supraspinatus fossa. There were thirteen shoulders with no and eleven
      shoulders with partial thickness supraspinatus tendon tears. In the forty cases
      with full thickness tendon tear, there was significant muscle atrophy and fatty
      infiltration. Atrophy of the fascial muscle portion was 43%, on the bony side it
      was 9% (p<0.005). The position of the central tendon within the supraspinatus
      fossa, was unaltered. Muscular changes following tendon tear occur highly
      asymmetrically: the muscle portion originating from the fascia primarily
      atrophies, the portion originating from the scapula primarily undergoes fatty
      infiltration. Muscular changes are not simply a consequence of muscle disuse, but
      dependent on architectural changes in the muscle.

PMID- 15734235
TI  - Rat supraspinatus muscle atrophy after tendon detachment.
AB  - Rotator cuff tears are one of the most common tendon disorders found in the
      healthy population. Tendon tears not only affect the biomechanical properties of
      the tendon, but can also lead to debilitation of the muscles attached to the
      damaged tendons. The changes that occur in the muscle after tendon detachment are
      not well understood. A rat rotator cuff model was utilized to determine the time
      course of changes that occur in the supraspinatus muscle after tendon detachment.
      It was hypothesized that the lack of load on the supraspinatus muscle would cause
      a significant decrease in muscle mass and a conversion of muscle fiber properties
      toward those of fast fiber types. Tendons were detached at the insertion on the
      humerus without repair. Muscle mass, morphology and fiber properties were
      measured at one, two, four, eight, and 16 weeks after detachment. Tendon
      detachment resulted in a rapid loss of muscle mass, an increase in the proportion
      of fast muscle fibers, and an increase in the fibrotic content of the muscle bed,
      concomitant with the appearance of adhesions of the tendon to surrounding
      surfaces. At 16 weeks post-detachment, muscle mass and the fiber properties in
      the deep muscle layers returned to normal levels. However, the fiber shifts
      observed in the superficial layers persisted throughout the experiment. These
      results suggest that load returned to the muscle via adhesions to surrounding
      surfaces, which may be sufficient to reverse changes in muscle mass.

PMID- 15734236
TI  - Healing of the aponeurosis during recovery from aponeurotomy: morphological and
      histological adaptation and related changes in mechanical properties.
AB  - Aponeurotomy, which is the transection of an aponeurosis perpendicular to its
      length, is performed to lengthen spastic and/or short muscles. During recovery,
      the cut ends of the aponeurosis are reconnected by new connective tissue bridging
      both ends. The aim of this study is to investigate the histological features of
      this new connective tissue as well as its mechanical properties after recovery
      from aponeurotomy. For this purpose, aponeurotomy was performed on the proximal
      aponeurosis of rat m. gastrocnemius medialis (GM), which was followed by six
      weeks of recovery. The lengths of aponeurotic tissues were measured as a function
      of active muscle length. The results are compared to a control group as well as
      to the acute effects and a sham operated group. Activation of the muscle at
      increasing lengths after aponeurotomy caused a gap between the cut ends of the
      aponeurosis. However, after recovery, new connective tissue is formed bridging
      the aponeurotic ends, consisting of thin collagen fibres, which are densely
      packed and generally arranged in the direction of the aponeurosis. The number of
      fibroblasts was three to five times higher than that of aponeurotic tissue of the
      intact parts as well as that of the acute and sham operated muscles. The strain
      of the new connective tissue as a function of active muscle length was shown to
      be about three times higher than that of the aponeurosis. It is concluded that
      the inserted new aponeurotic tissue is more compliant and that the aponeurosis
      becomes 10-15% longer than in untreated muscle. As a consequence, the muscle
      fibres located distally to the new aponeurotic tissue will become shorter than
      prior to aponeurotomy. This explains a shift of the length-force curve, which
      favours the restoration of the range of joint motion.

PMID- 15734237
TI  - The effect of shock wave treatment at the tendon-bone interface-an
      histomorphological and biomechanical study in rabbits.
AB  - PURPOSE: This study was performed to investigate the effect of shock wave
      treatment on the healing at tendon-bone interface in rabbits. MATERIALS AND
      METHODS: Thirty-six New Zealand White rabbits were used in this study. The
      anterior cruciate ligament was excised and replaced with the long digital
      extensor. The right knees (study group) were treated with 500 impulses of shock
      waves at 14 kV, while the left knees (control group) received no shock waves.
      Histomorphological studies were performed in 24 rabbits at 1, 2, 4, 8, 12 and 24
      weeks. Biomechanical studies were performed in 12 rabbits at 12 and 24 weeks.
      RESULTS: There was significantly more trabecular bone around the tendons noted in
      the study group compared with the control group at different time intervals after
      4 weeks (P<0.05). The contacting between bone and tendon was significantly better
      in the study group than the control group after 8 weeks (P<0.05). The tensile
      strength of the tendon-bone interface was significantly higher in the study group
      than the control group at 24 weeks (P=0.018), whereas similar modes of graft
      failure were noted between the two groups. CONCLUSION: Shock wave treatment
      significantly improves the healing rate of the tendon-bone interface in a bone
      tunnel in rabbits. The effect of shock waves appears to be time-dependent.

PMID- 15734238
TI  - Effects of age on the repair ability of mesenchymal stem cells in rabbit tendon.
AB  - Successful tissue engineered repair in the aging adult requires an abundant
      source of autologous, multipotent mesenchymal stem cells (MSCs). Although the
      number of bone marrow-derived MSCs declines dramatically with aging, their
      effectiveness in repair with increasing age has not been studied. We tested the
      hypothesis that MSCs harvested from geriatric rabbits would not repair patellar
      tendon defects as well as MSCs harvested from younger adult rabbits. In a novel
      within-subjects experiment, autologous MSCs were isolated from 1-year old
      rabbits, culture expanded, and cryogenically preserved. After housing the rabbits
      for 3 years, MSCs were re-harvested from the 4-year old rabbits and expanded.
      Five hundred thousand thawed and fresh MSCs were each separately mixed with type
      I collagen gel (333.3 x 10(3) cells/mg collagen) 24 h before surgery, and the
      resulting constructs implanted in bilateral full-length central third tendon
      defects. Twelve weeks post-surgery, the bone-tendon repair-bone units were failed
      in tension. Intra-animal (paired) comparisons between repair tissue treated with
      1-year old MSCs and repair tissue treated with 4-year old MSCs resulted in no
      significant differences (alpha=0.05) in material properties including maximum
      stress (10.8 MPa vs. 9.9 MPa; p=0.762), modulus (139.8 MPa vs. 146.2 MPa;
      p=0.914), and strain energy density (0.52 N mm/mm(3) vs. 0.53 N mm/mm(3);
      p=0.966). Despite an age-related trend, there were also no significant
      differences in structural properties including maximum force (62.9 N vs. 27.0 N;
      p=0.070), stiffness (24.9 N/mm vs. 12.0 N/mm; p=0.111), and strain energy (87.2 N
      mm vs. 31.4 N mm; p=0.061). A subset of the rabbits (n=4 1 yrMSC, n=2 4 yrMSC)
      showed the presence of ectopic bone in the repair region and were not included in
      the mechanical analyses. We conclude that in the rabbit model MSCs do not lose
      their benefit as a tendon repair therapy with aging and that MSCs can be
      cryogenically stored for 3 years and still effectively repair soft tissue
      injuries.

PMID- 15734239
TI  - Increase in sensory neuropeptides surrounding the Achilles tendon in rats with
      adjuvant arthritis.
AB  - The Achilles tendon in rats with adjuvant arthritis was analyzed by
      radioimmunoassay (RIA) and semi-quantitative immunohistochemistry for the
      occurrence of two sensory neuropeptides, substance P (SP) and calcitonin gene
      related peptide (CGRP), and a sensory modulating peptide, galanin (GAL). The
      tissue concentration of SP and CGRP in the Achilles tendon and its envelope, i.e.
      the paratenon and bony insertion, as assessed by RIA was increased by 22% and
      71%, respectively, compared to normal controls, whereas the level of GAL was
      unchanged. Semi-quantitative immunohistochemistry applied to different regions of
      the tendon in arthritic rats disclosed an increased occurrence of SP and CGRP
      positive nerve fibers in the paratenon and bone tendinous junction, whereas GAL
      fibers were only increased at the bone tendinous junction. Notably, neither
      neuropeptides nor inflammatory cells were seen in the tendon proper. The
      increased occurrence of SP and CGRP in the tendon envelope presumably reflects
      inflammatory actions, whereas that of GAL implies an endogenous anti-inflammatory
      response. The observed SP and CGRP upregulation in the paratenon and bony
      insertion suggests a pathophysiological role in paratenonitis and enthesitis
      often seen in patients with rheumatoid arthritis. Presumably Achillodynia
      originates in the tendon envelope rather than the tendon proper. The observations
      could be used to define new pharmacological targets for mitigating symptoms from
      tendons in rheumatoid arthritis and possibly also in other disorders. Whether a
      neuronal pathogenic mechanism underlies tendon overuse disorders in non-arthritic
      tendinopathies and the development of degeneration, i.e. tendinosis, remains to
      be studied.

PMID- 15734240
TI  - Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following
      botulinum toxin A injection: a study in rats.
AB  - PURPOSE: Botulinum toxin A (BoNT-A) is used to manage spasticity in cerebral
      palsy. BoNT-A cleaves SNAP-25 protein, blocking acetylcholine release and
      weakening the muscle. Nicotinic acetylcholine receptors (nAChR) including alpha,
      beta, delta, gamma, and epsilon subunits, and GAP-43 protein are associated with
      functional recovery of neuromuscular junctions (NMJ) following BoNT-A. To better
      understand the mechanism behind this functional recovery, this study attempted to
      (1) document changes in NMJ morphometry following BoNT-A, and (2) determine the
      gene expression of nAChR subunits, SNAP-25, and GAP-43 protein. METHODS: In this
      rat study (46 rats), 6 units/kg body weight of BoNT-A was injected into the
      gastrocnimus. NMJ morphometry and the time course of gene expression of nAChR
      subunits, SNAP-25, and GAP-43 were evaluated up to 1year post-injection. RESULTS:
      NMJ morphometry: gutter depth was reduced vs. the control side at two months, and
      normalizing by 6 months following BoNT. nAChR alpha mRNA and gamma mRNA increased
      by 3 days, peaked at 7 days and returned to control levels; delta mRNA peaked at
      3 days. Epsilon mRNA peaked by 7 days. SNAP-25 mRNA increased from 60 to 90 days,
      returning to control levels by 6 months. GAP-43 mRNA was unchanged. CONCLUSIONS:
      Specific nAChR subunit mRNA expression up-regulates and then returns to normal
      within two weeks, preceding changes in NMJ morphometry. Although GAP-43
      participates in nerve sprouting, no increase of GAP-43 mRNA occurred following
      BoNT-A. Delayed up-regulation of SNAP-25 mRNA might be associated with muscle
      functional recovery.

PMID- 15734241
TI  - Effects of systemic and regional taurine on skeletal muscle function following
      ischaemia-reperfusion injury.
AB  - INTRODUCTION: Tissues subjected to prolonged ischaemia are paradoxically further
      damaged when their perfusion is restored. The mechanisms underlying this
      ischaemia-reperfusion injury are complex, but oxidative attack is a central
      feature. Among the therapeutic agents used to attenuate ischaemia-reperfusion
      injury, endogenous agents such as taurine which form part of the native defence
      mechanism against oxidative damage are of particular interest. METHODS: Using a
      model of hindlimb ischaemia-reperfusion injury in the rat, taurine solution was
      administered either into the operated hindlimb, into the systemic circulation, or
      both. Contraction strengths of gastrocnemius biopsies from the operated and
      contralateral (control) hindlimbs of each animal were measured. RESULTS: Fast
      twitch strength was impaired significantly by ischaemia-reperfusion injury, and
      taurine injected into the operated limb conferred partial protection. A similar
      trend was observed for tetany, but protection by taurine was not statistically
      significant for tetanic contraction strength. CONCLUSION: Preservation of fast
      twitch strength following ischaemia-reperfusion injury by administration of
      taurine before ischaemia has clinical potential. However, delivery to the
      affected tissues during ischaemia presents technical difficulties.

PMID- 15734242
TI  - Ankle eversion torque response to sudden ankle inversion Torque response in
      unbraced, braced, and pre-activated situations.
AB  - In 13 young ankle stable subjects, ankle eversion torque and peroneal EMG were
      simultaneously recorded in response to sudden ankle inversion. The eversion
      torque response was bi-phasic. The initial development of torque, which was
      responsible for 30% of the maximal eversion torque response, was observed 135 ms
      after the start of platform rotation and correlated well with the onset of the
      automatic postural peroneal EMG response. The remaining eversion torque response
      commenced after 305 ms, strongly correlating with the onset of the peroneal long
      latency voluntary EMG activity. With the ankle unbraced, 66% of the maximal
      torque level was reached in 326 ms. While braced, the same torque magnitude was
      reached using 230 ms (p<0.02), and pre-activation of the peroneal muscles allowed
      the subjects to reach the same level of torque in 89 ms (p<0.0005). Prior to the
      study, a common reaction pattern to sudden inversion was expected in an ankle
      stable population, but review of the eversion torque and EMG data from the 13
      subjects revealed three different voluntary reaction patterns: 10 subjects showed
      an efficient activation of evertor muscles; two subjects stiffened their ankles
      with activation of both in- and evertor muscles; and one subject showed a
      marginal voluntary activation of the ankle evertors. The results of the study
      indicate that the reaction to sudden ankle inversion is not solely automatic. The
      main part of the torque response is voluntarily mediated and inter-individual
      differences in strategy seem to exist in healthy subjects.

PMID- 15734243
TI  - Age-related changes in electromyographic quadriceps activity during stair
      descent.
AB  - PURPOSE: To determine the effects of age on (i) the onset of vastus medialis
      obliquus (VMO) activity relative to that of vastus lateralis (VL) and (ii) the
      onset of quadriceps activity in terminal swing relative to heel-strike, during
      stair descent. METHODS: Sixty-six healthy men and women with no known knee
      pathology were recruited from the community and the University of Melbourne.
      Thirty-three older people aged over 50 (mean (SD) 68 (8) years) and 33 younger
      people aged under 40 (mean (SD) 25 (4) years) participated. Surface
      electromyography (EMG) was used to record muscle activity during stair descent.
      Muscle onset was identified from individual EMG traces with a computer algorithm
      and validated visually. RESULTS: Both younger and older participants demonstrated
      a relatively synchronous onset of VMO and VL (i.e. within 10ms of each other)
      with no differences between the age groups evident (P=0.262). However older
      participants activated their quadriceps significantly earlier than the younger
      group (P<0.001) even when differences in body mass and speed of stair descent
      were accounted for. CONCLUSION: Age-related changes in quadriceps activity are
      apparent. The clinical implications of such changes are unknown, but increases in
      joint loading are possible. Earlier quadriceps activation may compensate for
      balance and strength impairments in older people during challenging activities.

PMID- 15734244
TI  - A new tibial coordinate system improves the precision of anterior-posterior knee
      laxity measurements: a cadaveric study using Roentgen stereophotogrammetric
      analysis.
AB  - Roentgen stereophotogrammetric analysis (RSA) can be used to measure changes in
      anterior-posterior (A-P) knee laxity after anterior cruciate ligament (ACL)
      reconstruction. Previous measurements of A-P knee laxity using RSA have employed
      a tibial coordinate system with the origin placed midway between the tips of the
      tibial-eminences. However, the precision in measuring A-P knee laxity might be
      improved if the origin was placed on the flexion-extension axis of rotation of
      the knee. The purpose of this study was to determine whether a center-of-rotation
      tibial coordinate system with the origin placed midway between the centers of the
      posterior femoral condyles, which closely approximates the flexion-extension
      center-of-rotation of the knee, improves the precision in measuring A-P knee
      laxity compared to the tibial-eminence-based coordinate system. A-P knee laxity
      was measured using each coordinate system six times in three human cadaveric
      knees implanted with 0.8-mm diameter tantalum markers. For each laxity
      measurement, the knee was placed in a custom loading apparatus and biplanar
      radiographs were obtained while the knee resisted a 44 N posterior shear force
      and 136 N anterior shear force. A-P knee laxity was determined from the change in
      position of the tibia, with respect to the femur, resulting from the posterior
      and anterior shear forces. The precision for each coordinate system was
      calculated as the pooled standard deviation of A-P knee laxity measurements. The
      precision of the center-of-rotation coordinate system was 0.33 mm, which was
      about a factor of 2 better than the 0.62 mm precision of the tibial-eminence
      coordinate system (p=0.006). The 0.33 mm precision with the center-of-rotation
      coordinate system suggests that an observed change of either 0.56 mm (i.e. 1.7
      standard deviations) or greater in A-P knee laxity over time is a real change and
      not due to measurement error when the new tibial coordinate system is used and
      other factors contributing to variability are controlled as was done in this
      study. Accordingly, clinicians and researchers should consider the use of this
      alternate tibial coordinate system when making serial measurements of A-P knee
      laxity using RSA because the improved precision allows for the observation of
      smaller differences.

PMID- 15734245
TI  - Movement of the posterior cruciate ligament during knee flexion--MRI analysis.
AB  - The movement of the posterior cruciate ligament (PCL) during flexion of the
      living knee is unknown. The purpose of the present study was to analyze the
      movement of the PCL using magnetic resonance imaging (MRI). The posterior
      cruciate ligaments in 20 normal knees were visualized using MRI from extension to
      deep flexion. Sagittal inclination relative to the longitudinal axis of the tibia
      was measured and analyzed with reference to the patellar tendon (PT) and the
      anterior cruciate ligament (ACL). Although the PCL was slack in extension, it
      straightened with anterior inclination (24.1+/-5.1 degrees ) at 90 degrees
      flexion. At active maximum flexion (129.2+/-8.1 degrees ), the ligament was
      almost parallel (3.9+/-7.4 degrees inclination) to the longitudinal axis of the
      tibia. At passive maximum flexion (158.8+/-5.8 degrees ), the inclination was
      reversed anteroposteriorly, measuring -23.0+/-6.7 degrees . The PCL and PT moved
      in a corresponding manner within 20 degrees of discrepancy. The results of this
      in vivo study of the PCL have clinical relevance to conservative therapy for PCL
      knee injuries. The results of this study could also be useful in PCL
      reconstruction surgery to determine the optimum graft position to allow maximum
      postoperative motion.

PMID- 15734246
TI  - In vivo kinematics of the ACL during weight-bearing knee flexion.
AB  - No study has investigated the three-dimensional morphological changes of the
      anterior cruciate ligament (ACL) during functional activities in vivo. The
      purpose of this study was to analyze the elongation, rotation (twist), and
      orientation of the ACL during weight-bearing flexion in five human subjects using
      dual-orthogonal fluoroscopic images and MR image-based computer models. The ACL
      consistently decreased in length with flexion. At 90 degrees , the length
      decreased by 10% compared to its length at full extension. The ACL twisted
      internally by only 20 degrees at 30 degrees of flexion. The ACL was oriented more
      vertically (approximately 60 degrees ) and slightly laterally (approximately 10
      degrees ) at low flexion angles. These data on in vivo ligament elongation
      demonstrate that the ACL plays a more important role in lower flexion angles than
      at higher flexion angles during weight-bearing flexion. These data also suggest
      that successful ACL reconstruction should not only restore the ligament's
      elongation behavior, but also its rotational and orientation characteristics, so
      that normal ACL biomechanics are restored.

PMID- 15734247
TI  - Patellofemoral joint contact area increases with knee flexion and weight-bearing.
AB  - Patellofemoral pain is a common and debilitating disorder. Elevated cartilage
      stress of the patellofemoral joint is hypothesized to play a role in the onset of
      pain. Estimating cartilage stress requires accurate measurements of contact area.
      The purpose of this study was to estimate patellofemoral joint contact areas in a
      group of healthy, pain-free subjects during upright, weight-bearing conditions.
      Sixteen subjects (8 female, 8 male) were scanned in a GE Signa SP open
      configuration MRI scanner, which allowed subjects to stand or squat while
      reclining 25 degrees from vertical with the knee positioned at 0 degrees , 30
      degrees , or 60 degrees of flexion. A custom-built backrest enabled subjects to
      be scanned without motion artifact in both weight-bearing (0.45 body weight per
      leg) and reduced loading conditions ('unloaded' at 0.15 body weight) at each knee
      flexion posture. Male subjects displayed mean unloaded patellofemoral joint
      contact areas of 210, 414, and 520 mm(2) at 0 degrees , 30 degrees and 60 degrees
      of knee flexion, respectively. Female subjects' unloaded contact areas were
      similar at full extension (0 degrees ), but significantly smaller at 30 degrees
      and 60 degrees (p<0.01), with mean values of 269 and 396 mm(2), respectively.
      When normalized by patellar dimensions (heightxwidth), contact areas were not
      different between genders. Under weight-bearing conditions, contact areas
      increased by an average of 24% (p<0.05). This study highlights the differences in
      patellofemoral joint contact area between gender, knee flexion postures, and
      physiologic loading conditions.

PMID- 15734248
TI  - Cutaneous stimulation from patella tape causes a differential increase in vasti
      muscle activity in people with patellofemoral pain.
AB  - Patella taping reduces pain in individuals with patellofemoral pain (PFP),
      although the mechanism remains unclear. One possibility is that patella taping
      modifies vasti muscle activity via stimulation of cutaneous afferents. The aim of
      this study was to investigate the effect of stretching the skin over the patella
      on vasti muscle activity in people with PFP. Electromyographic activity (EMG) of
      individual motor units in vastus medialis obliquus (VMO) was recorded via a
      needle electrode and from surface electrodes placed over VMO and vastus lateralis
      (VL). A tape was applied to the skin directly over the patella and stretch was
      applied via the tape in three directions, while subjects maintained a gentle
      isometric knee extension effort at constant force. Recordings were made from five
      separate motor units in each direction. Stretch applied to the skin over the
      patella increased VMO surface EMG and was greatest with lateral stretch. There
      was no change in VL surface EMG activity. While there was no net increase in
      motor unit firing rate, it was increased in the majority of motor units during
      lateral stretch. Application of stretch to the skin over VMO via the tape can
      increase VMO activity, suggesting that cutaneous stimulation may be one mechanism
      by which patella taping produces a clinical effect.

PMID- 15734249
TI  - Contact pressures in the flexed hip joint during lateral trochanteric loading.
AB  - Acetabular fractures are an especially problematic outcome of motor vehicle side
      impacts. While fracture type has been correlated with impact direction and
      femoral orientation, actual contact pressures in the hip joint have not been
      quantified for lateral loading conditions. In the present study, we used pressure
      sensitive film to measure contact areas and pressures in seven hip joints from
      four cadavers under quasi-static lateral loading through the greater trochanter.
      The aim was to quantify the interactions of the femoral head with the acetabulum
      associated with variations in femoral orientation. Three angles of hip flexion
      (80 degrees , 90 degrees , 100 degrees ) and hip abduction (-10 degrees , 0
      degrees , 10 degrees ) were tested, producing nine test orientations for each
      joint. We observed that contact areas, pressures, and forces varied significantly
      with femoral orientation for the adducted hip. The principal locations of load
      transmission were in the anterior and posterior regions of the acetabulum. For
      the abducted femur, contact pressures were concentrated anteriorly, and with
      increased adduction, anterior contact pressures diminished while posterior and
      superior pressures increased. The movement of pressure sites was consistent with
      mechanisms of acetabular fractures described by Letournel and Judet and provides
      new data for validation of finite element models of the pelvis in side impact.

PMID- 15734250
TI  - Molecular chain stretch is a multiaxial failure criterion for conventional and
      highly crosslinked UHMWPE.
AB  - The development of accurate theoretical failure, fatigue, and wear models for
      ultra-high molecular weight polyethylene (UHMWPE) is an important step towards
      better understanding the micromechanisms of the surface damage that occur in load
      bearing orthopaedic components and improving the lifetime of joint arthoplasties.
      Previous attempts to analytically predict the clinically observed damage, wear,
      and fatigue failure modes have met with limited success due to the complicated
      interaction between microstructural deformations and continuum level stresses. In
      this work, we examined monotonic uniaxial and multiaxial loading to failure of
      UHMWPE using eight failure criteria (maximum principal stress, Mises stress,
      Tresca stress, hydrostatic stress, Coulomb stress, maximum principal strain,
      Mises strain, and chain stretch). The quality of the predictions of the different
      models was assessed by comparing uniaxial tension and small punch test data at
      different rates with the failure model predictions. The experimental data were
      obtained for two conventional (unirradiated and gamma radiation sterilized in
      nitrogen) and two highly crosslinked (150kGy, remelted and annealed) UHMWPE
      materials. Of the different failures models examined, the chain stretch failure
      model was found to capture uniaxial and multiaxial failure data most accurately
      for all of the UHMWPE materials. In addition, the chain stretch failure criterion
      can readily be calculated for contemporary UHMWPE materials based on available
      uniaxial tension data. These results lay the foundation for future developments
      of damage and wear models capable of predicting multiaxial failure under cyclic
      loading conditions.

PMID- 15734251
TI  - Polyethylene and titanium particles induce osteolysis by similar, lymphocyte
      independent, mechanisms.
AB  - Periprosthetic osteolysis is a major clinical problem that limits the long-term
      survival of total joint arthroplasties. Osteolysis is induced by implant-derived
      wear particles, primarily from the polyethylene bearing surfaces. This study
      examined two hypotheses. First, that similar mechanisms are responsible for
      osteolysis induced by polyethylene and titanium particles. Second, that
      lymphocytes do not play a major role in particle-induced osteolysis. To test
      these hypotheses, we used the murine calvarial model that we have previously used
      to examine titanium-induced osteolysis. Polyethylene particles rapidly induced
      osteolysis in the murine calvaria 5-7 days after implantation. The polyethylene
      induced osteolysis was associated with large numbers of osteoclasts as well as
      the formation of a thick periosteal fibrous tissue layer with numerous
      macrophages containing phagocytosed polyethylene particles. Polyethylene-induced
      osteolysis was rapidly repaired and was undetectable by day 21 after
      implantation. Lymphocytes were noted in the fibrous layer of wild-type mice.
      However, the amount of osteolysis and cytokine production induced by polyethylene
      particles was not substantially affected by the lack of lymphocytes in Pfp/Rag2
      double knock out mice. All of these findings are similar to our observations of
      osteolysis induced by titanium particles. These results provide strong support
      for both of our hypotheses: that similar mechanisms are responsible for
      osteolysis induced by polyethylene and titanium particles and that lymphocytes do
      not play a major role in particle-induced osteolysis.

PMID- 15734253
TI  - Endothelin-1 is secreted after total knee arthroplasty regardless of the use of a
      tourniquet.
AB  - Early infections and wound healing disorders after implantation of a total knee
      replacement occur regardless of the intraoperative use of a tourniquet. The
      biochemical regulatory processes responsible for the disturbances in
      microcirculation and thus the potential therapeutic options have yet to be
      elucidated. The hypothesis of the present paper was that endothelin-1 (ET-1), a
      mediator of microcirculation disturbances in parenchymatous organs, also is
      released after major operations on peripheral joints. The concentration of ET-1
      in the plasma was determined preoperatively and at 10 postoperative time points
      (5 min-48 h) with (group A, n=10) and without the use of a tourniquet (group B,
      n=10). The ET-1 concentration achieved its maximum 6h after opening the
      tourniquet, which corresponded to 3.3 times the preoperative value. Without a
      tourniquet, the concentration maximum (2.9 times the baseline value) was achieved
      already 1.5 h after the end of the operation. However, the total amount of ET-1
      secreted over 24 h was identical in both groups (p>0.5). We conclude that the
      tissue hypoxia resulting from the use of a tourniquet modulates ET-1 secretion,
      but that traumatization during the operation has a much stronger influence on the
      total amount secreted. ET-1 antagonists thus should be discussed for the drug
      prophylaxis of wound healing disorders, regardless of the use of a tourniquet.

PMID- 15734252
TI  - Lymphocyte responses in patients with total hip arthroplasty.
AB  - How lymphocyte-mediated metal sensitivity affects orthopaedic implant performance
      remains poorly understood. Do patients with implants exhibit elevated lymphocyte
      reactivity to metals and is this reactivity more generalized or more implant
      alloy specific? We investigated these questions by measuring lymphocyte responses
      to implant metals (Cr(+3), Co(+2), Ni(+2) at 0.1mM, and Ti(+4) at 0.001 mM) in
      six subject groups: Group 1a=young controls, Group 1b=age matched controls, Group
      2a=subjects with osteoarthritis (OA) and no history of metal sensitivity, Group
      2b=OA subjects with history of metal sensitivity, Group 3a=total hip arthroplasty
      (THA) subjects with no to mild radiographic osteolysis, and Group 3b=THA subjects
      with moderate osteolysis. Lymphocyte proliferation, using Lymphocyte
      Transformation Testing (LTT), and cytokine release provided quantitative
      reactivity measurement, where a stimulation index of >2 indicated metal
      sensitivity. OA subjects with a history of metal sensitivity (Group 2b) were more
      metal reactive to Ni than any other group, as expected (66% incidence and
      Stimulation Index >20). However, THA subjects (Groups 3a and b) were >3 fold more
      reactive to Cr (p<0.04), than were controls (Groups 1a & b) or OA subjects
      (Groups 2a & b). THA subjects with moderate vs mild osteolysis (Group 3b vs 3a)
      were more reactive to Co (43% vs 0% incidence). Only osteolytic THA subjects
      demonstrated increased cytokine responses with >two-fold (p<0.05) increases in
      soluble interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) levels in response
      to Cr challenge. This elevated incidence and averaged level of lymphocyte
      reactivity supports a metal-specific adaptive immune response and suggests
      involvement in the pathogenesis of poor implant performance, e.g. aseptic
      osteolysis.

PMID- 15734254
TI  - Circulating and synovial levels of IGF-I, cytokines, physical function and
      anthropometry differ in women awaiting total knee arthroplasty when compared to
      men.
AB  - PURPOSE: Determine if gender differences in osteoarthritis relate to cytokine and
      growth factor levels. METHODS: Cross-sectional comparison of serum and synovial
      concentrations of cytokines (IL-1alphabeta, TNF-alpha, IL-6), growth factors (IGF
      I, TGF-beta, IRAP), physical performance and perceived function in total knee
      arthroplasty candidates (TKAC) (n=17) and healthy controls (n=21) was done.
      RESULTS: Serum IGF-I values were reduced in female (TKAC 137.6+/-7.2; Controls
      160.2+/-26.2) but not male TKAC (TKAC 182.6+/-18.4; Controls 184.0+/-18.4)
      (p<0.05).). Serum and synovial levels of cytokines and growth factors did not
      differ significantly by group or gender. Physical performance testing (SPW, TUG)
      revealed significant group and gender differences (p=0.001) with women
      demonstrating greater functional impairment. DISCUSSION: A systemic, not local
      component to OA pathophysiology may exist for female TKAC. Male TKAC were less
      impaired, and their IGF-I levels differ little from Control values.

PMID- 15734255
TI  - Less systemic cytokine response in patients following microendoscopic versus open
      lumbar discectomy.
AB  - The magnitude of the tissue damage from surgery impacts the trauma response. This
      response is proportional to the severity of surgical stress. Systemic cytokines
      are recognized as markers of postoperative tissue trauma. Microendoscopic
      discectomy (MED) recently has become popular for treating lumbar disc
      herniations, and is associated with favorable clinical outcomes compared with
      open discectomy (OD). This study postulates that MED is a less traumatic
      procedure, and therefore has a lower surgical stress response compared to OD. In
      this study, a quantitative comparison of the overall effects of surgical trauma
      resulting from MED and OD was performed through analyzing patient systemic
      cytokines response. From April, 2002 to June, 2003, 22 consecutive patients who
      had symptomatic lumbar disc herniations were prospectively randomized to undergo
      either intracanalicular MED (N=10) or OD (N=12). In this study, the Vertebroscope
      System (Zeppelin, Pullach, Germany) was used to perform the endoscopic discectomy
      procedure in all MED patients. Serum levels of tumor necrosis factor-alpha (TNF
      alpha), Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), and Interleukin-8 (IL
      8) were measured before surgery and at 1, 2, 4, 8 and 24h after surgery using an
      enzyme-linked immunosorbent assay. Serum C-reactive protein (CRP) was measured at
      the same time interval. The results showed the MED patients had shorter
      postoperative hospital stay (mean, 3.57+/-0.98 vs. 5.92+/-2.39 days, p=0.025) and
      less intraoperative blood loss (mean, 87.5+/-69.4 vs. 190+/-115 ml, p=0.042). The
      operating length, including the set-up time, was longer in the MED group (mean,
      109+/-35.9 vs. 72.1+/-17.8 min, p=0.01). The mean size of skin incision made for
      the MED patients was 1.86+/-0.13 cm (range 1.7-2.0 cm); and 6.3+/-0.98 cm for the
      OD patients (range 5.5-8 cm), p=0.001. The patients' pain severity of the
      involved limbs on 10-point Visual Analog Scale before operation in MED group was
      7.5+/-0.3 (range 6-9) and 8+/-0.2 (range 7-9) in OD group, p=0.17; and after
      surgery, 1.5+/-0.2 (range 1-2) in MED group and 1.4+/-0.1 (range 1-3) in OD
      group, p=0.91. CRP levels peaked at 24h in both groups, and OD patients displayed
      a significantly greater postoperative rise in serum CRP (mean, 27.78+/-15.02 vs.
      13.84+/-6.25mg/l, p=0.026). Concentrations of TNF-alpha, IL-1beta, and IL-8 were
      detected only sporadically. Serum IL-6 increased less significantly following MED
      than after OD. In the MED group, IL-6 level peaked 8h after surgery, with the
      response statistically less than in the open group (mean, 6.27+/-5.96 vs. 17.18+/
      11.60 pg/ml, p=0.025). A statistically significant correlation was identified
      between IL-6 and CRP values (r=0.79). Using the modified MacNab criteria, the
      clinical outcomes were 90% satisfactory (9/10) in MED patients and 91.6%
      satisfactory (11/12) in OD patients at a mean 18.9 months (range 10-25) follow
      up. Based on the current data, surgical trauma, as reflected by systemic IL-6 and
      CRP response, was significantly less following MED than following OD. The
      difference in the systemic cytokine response may support that the MED procedure
      is less traumatic. Moreover, our MED patients had achieved satisfactory clinical
      outcomes as the OD patients at a mean 18.9 months follow-up after surgery.

PMID- 15734256
TI  - Experimental studies on the effects of recombinant human matrix
      metalloproteinases on herniated disc tissues--how to facilitate the natural
      resorption process of herniated discs.
AB  - PURPOSE: Recently, MMP-7 and MMP-3 have been found to play a crucial role in the
      natural resorption process of herniated discs. We therefore examined the role of
      these recombinant human matrix metalloproteinases (rh MMPs) in the treatment of
      herniated discs. METHODS: (a) Surgical samples of herniated disc were cultured in
      the presence or absence of rh MMPs, and wet weight was measured 24h later. (b)
      The rh MMPs were administered into normal rabbit intervertebral discs, and after
      1 week spine samples were stained with Safranin O. (c) The rh MMPs were
      administered into canine herniated discs in vivo. Myelography and MRI were
      performed prior to and 1 week after administration. Spine samples were examined
      histologically. Whole disc tissue was collected, total protein was extracted, and
      Western blot analysis was performed. RESULTS: (a) Proteoglycan degradation was
      found in MMP-7, MMP-3, and chymopapain-treated samples. MMP-7 and chymopapain
      treated samples displayed a significant loss in wet weight (p<0.01). (b) Normal
      disc tissues after administration of rh MMP-7, MMP-3, and chymopapain showed an
      extensive loss of Safranin O staining. (c) The rh MMP-7-treated discs had a
      marked decrease in protruded herniation by MRI. Herniated discs after
      administration of MMP-7 and chymopapain showed a significant decrease in
      protruded mass 7 days after administration compared with saline-treated discs
      when evaluated by myelography (p<0.01). The rh MMP-7-treated discs displayed a
      clear loss of Safranin O staining in the nucleus pulposus. Proteoglycan
      expression was barely detectable in disc tissues after MMP-7 administration,
      whereas obvious expression was obtained in saline-treated or untreated disc
      tissues. CONCLUSIONS: Exposure to rh MMP-7 resulted in promising proteoglycan
      loss in human surgical samples, normal rabbit intervertebral discs, and natural
      canine herniated discs. Administration of rh MMP-7 may facilitate the resorption
      process of herniated discs.

PMID- 15734257
TI  - Effect of acute nerve root compression on endoneurial fluid pressure and blood
      flow in rat dorsal root ganglia.
AB  - The objective of the current study was to test the hypothesis that crush injury
      to nerve root increases endoneurial fluid pressure (EFP) and decreases blood flow
      in the associated dorsal root ganglion (DRG). A total of 21 adult, female Sprague
      Dawley rats had their left L5 nerve root and DRG exposed. The L5 nerve root was
      clamped for 2 s with a vascular suture clip just proximal to the DRG (compression
      group). Sham-operated animals without compression were used for control (control
      group). EFP was recorded with a servo-null micropipette system using a glass
      micropipette with tip diameter of 4 mum before and after 3 h of treatment. After
      the final measurement of EFP, DRG was excised and processed for histology. Blood
      flow in the DRG was continuously monitored by laser Doppler flow meter for 3 h.
      Three hours after treatment, EFP was 4.7+/-2.7 cm H(2)O in the compression group
      and 2.2+/-1.2 cm H(2)O in the control group (P<0.05). Edema was the principal
      pathologic findings seen consistently in the DRG from animals in the compression
      group. Blood flow in the compression group was reduced 10 min after compression.
      This reduction was statistically significant compared with that of the control
      (P<0.01). An acute compression to the nerve root increased endoneurial edema,
      increased EFP in the associated DRG, and reduced DRG blood flow. This combination
      of increased EFP and decreased blood flow in the DRG may result in neuronal
      ischemia and sensory dysfunction. These acute pathophysiologic changes may thus
      have a role in the pathogenesis of low back pain and sciatica due to disc
      herniation and spinal canal stenosis.

PMID- 15734258
TI  - Rapid phenotypic changes in passaged articular chondrocyte subpopulations.
AB  - Articular chondrocytes are often expanded in vitro and then used to assist in
      healing articular cartilage defects. We investigated the extent of
      dedifferentiation in monolayer-passaged, zonal articular chondrocytes by using
      quantitative, real-time PCR. The relative gene expressions for collagen type I
      and II, aggrecan, and superficial zone protein were analyzed for relevant passage
      numbers (P0-P4) to determine how the expansion of chondrocytes affects the
      expression of cartilage extracellular matrix proteins. Results reveal that
      dramatic changes occur as early as first passage. Furthermore, these changes are
      shown to persist even when the expanded cells are encapsulated in 3D, alginate
      beads. Successful tissue engineering and autologous cell transplantation
      procedures rely heavily on having a cell source that expresses the chondrocytic
      phenotype. The results of this study suggest that major problems exist at the
      front-end of cartilage regeneration efforts.

PMID- 15734259
TI  - Growth and integration of neocartilage with native cartilage in vitro.
AB  - Poor integration of neocartilage with recipient has been a major obstacle to
      articular cartilage restoration. An in vitro study was designed to provide
      insights regarding the integration process. Cartilage explants and chondrocytes
      were harvested from the distal sternum of 16-day-old chick embryos. Four million
      chondrocytes and one 1mm(3) explant were centrifuged together in a 0.75ml tube.
      In the constructs, consisting of cartilage explant and chondrocyte pellet,
      isolated chondrocytes attached to the surface of the explant at the beginning of
      the culture, followed by significant chondrocyte death at the interface between
      chondrocyte pellet and explant. Chondrocyte apoptosis was seen almost exclusively
      at this interface. Meanwhile, the interface was a zone with active extracellular
      matrix deposition as demonstrated by immunohistochemistry. By two weeks, the
      junction of neocartilage and native cartilage explant had formed an acellular
      zone with collagen fibrils orientated parallel with the surface of the cartilage
      explant. In conclusion, chondrocyte death leads to acellularity and fibril
      network reorganization at the neocartilage/explant interface, and impacts the
      quality of cartilage repair as abnormal matrix remodeling implies.

PMID- 15734260
TI  - Inhibition of nitric oxide can ameliorate apoptosis and modulate matrix protein
      gene expression in bacteria infected chondrocytes in vitro.
AB  - Bacterial infection stimulates nitric oxide (NO) production in chondrocytes.
      However, the role of NO in chondrocyte apoptosis after infection remains unclear.
      The purpose of the study was to test if inhibition of NO could ameliorate
      apoptosis and modulate matrix protein gene expression in bacteria-infected
      chondrocytes. It was shown that pre-treating chondrocytes with L-NAME (1 mM)
      significantly decreased the release of NO (from 72 to 14 microM) and the extent
      of apoptosis (from 52.9% to 18.9%). Pre-treatment with L-NAME also counteracted
      the bacteria-induced downregulation of Type II collagen (from 26% to 79%) and
      aggrecan (from 63% to 105%) mRNA levels. Inhibition of NO after the induction of
      infection could not decrease the extent of apoptosis and modulate matrix protein
      gene expression. The results of this study support the hypothesis that NO has an
      important role in bacteria-induced chondrocyte apoptosis. Pre-treatment but not
      post-treatment could ameliorate the extent of apoptosis and reestablish the
      cartilage matrix protein gene expression. This study suggests that in addition to
      NO, other mechanisms may be responsible for the sustained destruction of
      articular cartilage in the post-infectious arthropathy.

PMID- 15734261
TI  - Type I and II collagen regulation of chondrogenic differentiation by mesenchymal
      progenitor cells.
AB  - Chondrogenic differentiation by mesenchymal progenitor cells (MPCs) is associated
      with cytokines such as transforming growth factor-beta 1 (TGF-beta1) and
      dexamethasone. Extracellular matrix (ECM) also regulates the differentiation by
      MPCs. To define whether ECM plays a functional role in regulation of the
      chondrogenic differentiation by MPCs, an in vitro model was used. That model
      exposed to dexamethasone, recombinant human TGF-beta1(rhTGF-beta1) and collagens.
      The results showed that MPCs incorporated with dexamethasone and rhTGF-beta1
      increased proliferation and expression of glycosaminoglycan (GAG) after 14 days.
      Type II collagen enhanced the GAG synthesis, but did not increase alkaline
      phosphatase (ALP) activity. When adding dexamethasone and rhTGF-beta1 MPCs
      increased mRNA expression of Sox9. Incorporation with type II collagen,
      dexamethasone and rhTGF-beta1, MPCs induced mRNA expression of aggrecan and
      enhanced levels of type II collagen, and Sox9 mRNA. In contrast, incorporation
      with type I collagen, dexamethasone and rhTGF-beta1 MPCs reduced levels of
      aggrecan, and Sox9 mRNA, and showed no type II collagen mRNA. Altogether, these
      results indicate that type I and II collagen, in addition to the cytokine effect,
      may play a functional role in regulating of chondrogenic differentiation by MPCs.

PMID- 15734262
TI  - p38 MAPK and COX2 inhibition modulate human chondrocyte response to TGF-beta.
AB  - These studies compare actions of p38 MAPK inhibition and COX2 inhibition to
      modulate human arthritic chondrocyte responses to TGF-beta and FCS under basal
      and IL-1 activated conditions. Chondrocytes isolated from arthritic human femoral
      condyle cartilage obtained at total knee replacement were grown to 80%
      confluence. Proteoglycan synthesis and proliferation were measured with and
      without IL-1 activation in the presence and absence of growth factors and with
      and without inhibition of p38 MAPK or COX2 activity. Experiments to evaluate TIMP
      1 production under these conditions were done using cartilage organ cultures.
      Neither p38 MAPK inhibitors nor COX2 inhibition affected basal proliferation.
      However both inhibitors enhanced the proliferative response to TGF-beta and FCS
      in IL-1 activated chondrocytes. TGF-beta stimulated proteoglycan synthesis was
      decreased by p38 MAPK inhibition, however COX2 inhibition restored the response
      to TGF-beta in IL-1 activated cells. In contrast, COX2 inhibition did not
      modulate TIMP-1 production while p38 MAPK inhibitors potentiated TGF-beta
      stimulated production of TIMP-1 in IL-1 activated cartilage. p38 MAPK inhibition
      and COX2 inhibition have unique and similar abilities to counteract some of the
      effects of IL-1 on human chondrocyte/cartilage metabolism. Both will partially
      restore the proliferative response to growth factors. p38 MAPK inhibition blunts
      TGF-beta stimulation of proteoglycan synthesis, but increases TIMP-1 synthesis.
      COX2 inhibition can restore the proteoglycan synthetic response to TGF-beta, but
      has no effect on cartilage TIMP-1 production. Use of these inhibitors to minimize
      cartilage damage in arthritic and mechanically stressed joints should reflect
      these characteristics.

PMID- 15734263
TI  - Molecular mechanism of nitric oxide-induced osteoblast apoptosis.
AB  - Nitric oxide (NO) can regulate osteoblast activities. Our previous study showed
      that NO induced osteoblast apoptosis. This study was further aimed to evaluate
      the mechanism of NO-induced osteoblast apoptosis from the viewpoints of
      mitochondrial functions, intracellular oxidative stress, and the anti-apoptotic
      Bcl-2 protein using neonatal rat calvarial osteoblasts as the experimental model.
      Exposure of osteoblasts to sodium nitroprusside (SNP), an NO donor, significantly
      increased amounts of lactate dehydrogenase in the culture medium, and decreased
      cell viability in concentration- and time-dependent manners. Administration of
      SNP in osteoblasts time-dependently led to DNA fragmentation. The mitochondrial
      membrane potential was significantly reduced following SNP administration. SNP
      decreased complex I NADH dehydrogenase activity in a time-dependent manner.
      Levels of cellular adenosine triphosphate (ATP) were suppressed by SNP. In
      parallel with the mitochondrial dysfunction, SNP time-dependently increased
      levels of intracellular reactive oxygen species. Immunoblotting analysis revealed
      that SNP reduced Bcl-2 protein levels. Exposure to lipopolysaccharide (LPS) and
      IFN-gamma significant increased endogenous nitrite production. In parallel with
      the increase in endogenous NO, administration of LPS and IFN-gamma suppressed
      cell viability, mitochondrial membrane potential, and ATP synthesis. Results of
      this study show that NO released from SNP can induce osteoblast insults and
      apoptosis, and the mechanism may involve the modulation of mitochondrial
      functions, intracellular reactive oxygen species, and Bcl-2 protein.

PMID- 15734264
TI  - Vascular endothelial growth factor (VEGF) gene transfer enhances surgical
      revascularization of necrotic bone.
AB  - Avascular necrosis of bone is a relatively common clinical condition caused by
      inflammatory conditions, steroid or other drug use, and trauma that affect many
      different sites in man. Revascularization of the necrotic bone is slow to occur,
      often resulting in bone resorption and eventual collapse of the involved bone.
      Rapid revascularization and subsequent bone remodeling may lead to improved
      outcomes. Surgical revascularization with arterovenous bundles (AV bundles) or
      vascularized bone grafts results in neoangiogenesis and bone remodeling. Gene
      transfer of an angiogenic factor to the vessel wall may be an additional strategy
      to further accelerate this process. In this study, we examined the effectiveness
      of vascular endothelial growth factor (VEGF) gene transfer to augment surgical
      revascularization of necrotic bone. An adenoviral vector, either with the VEGF
      gene (VEGF-A) or identical virus without the cDNA VEGF insert (ADV-DeltaE1) was
      used to transduce endothelial cells in rabbit saphenous arteries. The artery was
      then placed with its venae comitantes as an AV bundle into necrotic iliac crest
      bone in vivo. Angiogenesis in the necrotic bone was quantified by bone blood flow
      measurement and assessment of vessel density following microangiography. The
      extent of neoangiogenesis was significantly greater in the VEGF group than the
      control group at 1 week postoperatively.

PMID- 15734265
TI  - The effect of bone microstructure on the initiation and growth of microcracks.
AB  - Osteonal bone is often compared to a composite material and to metals as
      discontinuities within the material may provide sites of stress concentration for
      crack initiation and serve as barriers to crack growth. However, little
      experimental data exist to back up these hypotheses. Fluorescent chelating agents
      were applied at specific intervals to bone specimens fatigue tested in cyclic
      compression at a stress range of 80 MPa. The failed specimens were sectioned and
      labelled microcracks identified using UV epifluorescence microscopy. Microcrack
      lengths were measured and their relationship to cement lines surrounding
      secondary osteons recorded. Microcrack length at the time of encountering a
      cement line was also measured. Microcracks of less than 100mum stopped growing
      when they encountered a cement line. Microcracks of greater than 100mum in length
      continued to grow after encountering a cement line surrounding an osteon. Only
      microcracks greater than 300mum in length were capable of penetrating osteons and
      these microcracks were the only ones which were observed to cause failure in the
      specimen. These experimental data support the hypothesis that secondary osteons
      act as barriers to crack propagation in compact bone. However, it shows that this
      microstructural barrier effect is dependent on the crack length at the time of
      encountering an osteon. For the vast majority of cracks, osteons act as barriers
      to growth but for the minority of cracks that are long enough and do break
      through the cement line, an osteon may actually act as a weakness in the bone and
      facilitate crack propagation.

PMID- 15734267
TI  - Intact fibula improves fracture healing in a rat tibia osteotomy model.
AB  - Rat tibia fractures are often used in fracture healing studies. Usually the
      fracture is stabilized with an intramedullary pin, which provides bending
      stiffness, but little torsional stiffness. The objective of this research was to
      determine the in vitro torsional rigidity of an osteotomized tibia with and
      without the fibula, and to determine if this difference influences the healing
      process in vivo. In vitro eleven rat tibias received an osteotomy, were
      stabilized with an intramedullary pin, and were tested in internal rotation to
      determine the torsional rigidity. The fibula was then manually broken and the
      torsional rigidity measured again. In vivo 18 rats received a tibial osteotomy,
      eight of which had an additional fractured fibula. After three weeks, the rats
      were sacrificed and the tibias were analyzed. Bone density in the fracture callus
      was measured with qCT. Bending rigidity and maximum breaking moment were
      determined in three-point bending. In vitro testing demonstrated that the
      torsional rigidity with an intact fibula was nearly two times higher than when
      the fibula was fractured. Though the torsional rigidity was still small in
      comparison with an intact bone, it resulted in a significantly different healing
      process in vivo. Rats with intact fibulas had significantly higher bone mineral
      density, bending rigidity, and maximum breaking moment compared to rats with a
      fractured fibula. These results indicate that torsional stability considerably
      affects the healing process. In a fracture model, it is critical to characterize
      the mechanical environment of the fracture.

PMID- 15734266
TI  - Accuracy and precision of radiostereometric analysis in the measurement of three
      dimensional micromotion in a fracture model of the distal radius.
AB  - The purpose of the current study was to verify the feasibility of
      radiostereometric analysis (RSA) in monitoring three-dimensional fracture
      micromotion in fractures of the distal radius. The experimental set-up consisted
      of a simulated model of an extra-articular Colles' fracture, including metallic
      beads inserted into the bone on either side of the fracture site. The model was
      rigidly fixed to high precision micrometer stages allowing controlled translation
      in three axes and rotation about the longitudinal and transverse axes. The whole
      construct was placed inside a RSA calibration cage with two perpendicular
      radiographic film cassettes. Accuracy was calculated as the 95% prediction
      intervals from the regression analyses between the micromotion measured by RSA
      and actual displacements measured by micrometers. Precision was determined as the
      standard deviation of five repeated measurements of a 200 microm displacement or
      a 0.5 degrees rotation along a specific axis. Translations from 25 microm to 5mm
      were measured with an accuracy of +/-6 microm and translations of 200 microm were
      measured with a precision of 2-6 microm. Rotations ranging from 1/6 degrees to 2
      degrees were measured with an accuracy of +/-0.073 degrees and rotations of 1/2
      degrees were measured with a precision of 0.025 degrees -0.096 degrees . The
      number of markers and their configuration had greater impact on the accuracy and
      precision of rotation than on those of translation. Aside from the unknown rate
      of clinical marker loosening, the current results favor the use of at least four
      markers in each bone fragment in distal radius fractures. These results suggest a
      strong rationale for the use of RSA as an objective tool for comparing different
      treatment modalities and novel bone graft substitutes aimed at stabilization of
      fractures of the distal radius.

PMID- 15734268
TI  - In vivo assessment of regenerate axial stiffness in distraction osteogenesis.
AB  - This paper presents an in vivo test for assessment of regenerate axial stiffness
      after the distraction phase of lengthening therapy. The test result supplements
      radiography in evaluating bone healing and assists in determining when the
      regenerate stiffness is sufficient for removal of the external fixator. The test
      is non-invasive and does not require fixator removal. The theoretical basis for
      the method is that an externally applied load is shared between the fixator and
      the regenerating bone. The amount of load carried by the regenerate depends on
      its axial stiffness, which increases with advanced mineralization. By measuring
      the force in the fixator while applying a known external load to the limb, the
      load-share ratio between fixator and limb can be assessed. A load-share ratio of
      100% indicates that the entire load is carried by the fixator. The ratio
      decreases as the regenerate structure gradually stiffens. In a clinical trial of
      22 individuals with tibial lengthening, the fixator was removed when the load
      share ratio dropped below 10%. None of the patients experienced fracture after
      removal of the fixator.

PMID- 15734269
TI  - Gender and alcohol moderate prenatal cocaine effects on teacher-report of child
      behavior.
AB  - Prenatal cocaine exposure has been associated with behavior problems at school
      age. However, the correspondence between use of cocaine and alcohol during
      pregnancy is often high, making appropriate allocation of variance and control
      for other exposures and their interactions difficult. Additionally, gender
      specific effects are not typically reported. The purpose of the current study was
      to determine the degree to which gender-specific effects of prenatal cocaine
      exposure on teacher-reported child externalizing behavior problems were evident
      when evaluated in relation to prenatal alcohol exposure. Subjects were singleton
      infants of mothers who were prospectively evaluated during pregnancy. At age
      seven, 499 children (214 exposed prenatally to cocaine) were evaluated in our
      laboratory and teacher reports were solicited. Analyses stratified by gender and
      prenatal alcohol exposure status, and controlled for significant pre- and
      postnatal confounders, revealed that among boys with prenatal alcohol exposure,
      those with persistent cocaine exposure throughout pregnancy had significantly
      higher levels of Delinquent Behavior compared to boys with no cocaine exposure.
      Boys with any prenatal cocaine exposure were twice as likely as unexposed boys to
      have clinically significant Externalizing Behavior scores. However, no
      association was found between prenatal cocaine exposure and scores on
      Externalizing Behavior and specific syndromes for boys with no prenatal alcohol
      exposure. Among girls with no prenatal alcohol exposure, those with persistent
      cocaine exposure had significantly higher levels of Externalizing Behaviors and
      Aggressive Behaviors compared to girls with no prenatal cocaine exposure after
      control for confounding, and were almost five times as likely to have clinically
      significant Externalizing Behavior scores. However, for girls with prenatal
      alcohol exposure, no association between prenatal cocaine exposure and scores on
      Externalizing Behavior and specific syndromes was found after control for
      confounding. The current findings support gender- and alcohol-moderated effects
      of prenatal cocaine exposure on school-age teacher-reported child behavior
      problems. These findings are similar to what we have reported for independent
      parent-reported behavioral evaluation.

PMID- 15734270
TI  - Gender and alcohol moderate caregiver reported child behavior after prenatal
      cocaine.
AB  - OBJECTIVE: The concurrence of prenatal alcohol exposure with other drug exposure,
      low socioeconomic status and environmental risk factors may obscure associations,
      if any, between prenatal cocaine exposure and child outcomes. This study
      evaluates the effects of prenatal cocaine exposure on child behavior in analyses
      stratified by gender and prenatal alcohol exposure status. METHODS: Maternal
      alcohol, cigarette, and illicit drug use were prospectively assessed by interview
      during pregnancy and postnatally. Maternal and neonatal urine were tested for
      drug exposure as clinically indicated. Caregiver report of child behavior was
      assessed with the Achenbach Child Behavior Checklist (CBCL). Dichotomous cocaine
      exposure was characterized as no (negative history and biologic markers), and any
      (positive history and/or biologic markers during pregnancy and/or positive urine
      screen at delivery from either mother or infant). RESULTS: Prenatal cocaine
      exposure was associated with adverse effects on offspring behavior that were
      moderated by the gender of the offspring as well as prenatal alcohol exposure.
      For girls without prenatal alcohol exposure, 6.5% of the unique variance in
      behavior was related to prenatal cocaine exposure. For these girls, the odds of
      scoring in the abnormal range for Aggression was 17 times control levels (95%
      confidence limits 1.4 to 203). These findings, though significant, have wide
      confidence intervals and need to be replicated in larger cohorts and on
      longitudinal follow-up.

PMID- 15734271
TI  - School performance of children with gestational cocaine exposure.
AB  - OBJECTIVE: To document school performance (pass/fail, grade point average,
      reading level, standardized test scores, absences) of cocaine-exposed and control
      children. DESIGN: A total of 135 children (62 with gestational cocaine exposure
      and 73 without), who were enrolled at birth, followed prospectively and have
      completed the fourth grade, were evaluated using report card data, standardized
      test results, teacher and parent report, and natal and early childhood data.
      Successful grade progression was defined as completing grades 1 through 4 without
      being retained. RESULTS: Cocaine-exposed (cocaine-exposed presented first) and
      control children were similar in school performance: successful grade progression
      (71% vs. 84%), Grade Point Average (2.4+/-0.8 vs. 2.6+/-0.7), reading below grade
      level (30% vs. 28%) and standardized test scores below average (reading [32% vs.
      35%], math [57% vs. 44%], science [39% vs. 36%]); all p > or = 0.10. Children
      with successful progression, regardless of cocaine exposure, had higher Full
      Scale Intelligence Quotient and better home environments. CONCLUSION: In this
      inner-city cohort, cocaine-exposed and control children had similar poor school
      performance. Better home environment and higher Intelligence Quotient conferred
      an advantage for successful grade progression, regardless of gestational cocaine
      exposure.

PMID- 15734272
TI  - Predictors of motor development in children prenatally exposed to cocaine.
AB  - The current study examined the pattern of motor development across the first 18
      months of life in infants with in utero exposure to cocaine to determine how
      prenatal drug effects and level of exposure relates to motor development. Motor
      development was examined at 1, 4, 12, and 18 months of age (corrected for
      prematurity). Infants were divided into cocaine exposed (n=392) and comparison
      (n=776) groups. Exposure status was determined by meconium assay and maternal
      self-report with alcohol, marijuana, tobacco, and opiates present in both groups.
      Motor skills were assessed at 1 month using the NICU Network Neurobehavioral
      Scale (NNNS), at 4 months using the posture and fine motor assessment of infants
      (PFMAI), at 12 months using the Bayley Scales of Infant Development-Second
      Edition (BSID-II), and at 18 months using the Peabody Developmental Motor Scales
      (PDMS). Examiners masked to exposure status performed all assessments. Motor
      scores were converted to standard (z) scores, and hierarchical linear modeling
      (HLM) was used to examine the change in motor skills from 1 to 18 months of age.
      Infants with exposure to cocaine showed low motor skills at their initial status
      of 1 month but displayed significant increases over time. Both higher and lower
      levels of tobacco use related to poorer motor performance on average. Heavy
      cocaine use related to poorer motor performance as compared to no use, but there
      were no effects of level of cocaine use on change in motor skills.

PMID- 15734273
TI  - Marijuana impairs growth in mid-gestation fetuses.
AB  - Marijuana (Cannabis sativa) is the most commonly used illicit drug by pregnant
      women, but information is limited about the effects of prenatal cannabis exposure
      on fetal development. The present study evaluated the influence of early maternal
      marijuana use on fetal growth. Women electing voluntary saline-induced abortions
      were recruited at a mid-gestational stage of pregnancy (weeks 17-22), and
      detailed drug use and medical histories were obtained. Toxicological assays
      (maternal urine and fetal meconium) were used in conjunction with the maternal
      report to assign groups. Subjects with documented cocaine and opiate use were
      excluded. Main developmental outcome variables were fetal weight, foot length,
      body length, and head circumference; ponderal index was also examined. Analyses
      were adjusted for maternal alcohol and cigarette use. Marijuana (n=44)- and
      nonmarijuana (n=95)-exposed fetuses had similar rates of growth with increased
      age. However, there was a 0.08-cm (95% CI -0.15 to -0.01) and 14.53-g (95% CI 
      28.21 to 0.86) significant reduction of foot length and body weight,
      respectively, for marijuana-exposed fetuses. Moreover, fetal foot length
      development was negatively correlated with the amount and frequency of marijuana
      use reported by the mothers. These findings provide evidence of a negative impact
      of prenatal marijuana exposure on the mid-gestational fetal growth even when
      adjusting for maternal use of other substances well known to impair fetal
      development.

PMID- 15734274
TI  - Neurocognitive consequences of marihuana--a comparison with pre-drug performance.
AB  - In determining the effects of regular marihuana use on neurocognition, abilities
      within specific relevant cognitive domains prior to regular drug use have not
      been available. The present study examined effects of current and past regular
      use of marihuana in subjects for whom pre-drug performance had been ascertained
      in a prospective, longitudinal fashion. A total of 113 young adults, assessed
      since infancy, were evaluated using neurocognitive tests for which commensurate
      measures were obtained prior to the initiation of marihuana smoking. Marihuana
      users, determined by urinalysis and self-report, were categorized as light (< 5
      joints per week) and heavy (> or = 5 joints per week) current users and former
      users, the latter having used the drug regularly in the past (> or = 1 joint per
      week) but not for at least 3 months. A third of the subjects were using marihuana
      on a regular basis at the time of assessment with half being heavy users. Among
      former, regular users, approximately half had been smoking 5 or more joints per
      week. Overall IQ, memory, processing speed, vocabulary, attention, and abstract
      reasoning were assessed. After accounting for potentially confounding factors and
      pre-drug performance in the appropriate cognitive domain, current regular heavy
      users did significantly worse than non-users in overall IQ, processing speed,
      immediate, and delayed memory. In contrast, the former marihuana smokers did not
      show any cognitive impairments. It was concluded that residual marihuana effects
      are evident beyond the acute intoxication period in current heavy users after
      taking into account pre-drug performance but similar deficits are no longer
      apparent 3 months after cessation of regular use, even among former heavy using
      young adults.

PMID- 15734275
TI  - Does selenium deficiency unmask mercury toxicity in motor neurons?
AB  - OBJECTIVE: Inorganic mercury enters in particular motor neurons and has been
      implicated in motor neuron diseases. One way that cells protect themselves from
      mercury toxicity is via selenium, so we sought to determine whether the motor
      neurons of mice on a low selenium diet would be more susceptible to mercury
      toxicity. METHODS: Recently weaned mouse pups were placed on diets containing
      either low, normal or high levels of selenium. Twenty days later, half were
      exposed to mercury vapor. Ninety days after exposure, their spinal motor neurons
      and phrenic motor axons were examined histologically. Mercury in the spinal cord
      was sought using autometallography. RESULTS: Neither low nor high selenium diets
      combined with mercury vapor had any clinical effect on the mice. Mercury was seen
      within the spinal motor neurons of all exposed mice. Spinal motor neurons and
      phrenic motor axons however appeared normal in morphology and size across the
      groups. CONCLUSION: Diets low or high in selenium did not damage motor neurons
      with or without mercury. This suggests that changes in the selenium environment
      are unlikely to precipitate mercury toxicity in motor neurons.

PMID- 15734277
TI  - Neuropsychological effects of long-term exposure to organophosphate pesticides.
AB  - Cholinesterase inhibitors, such as carbamates and organophosphates (OPs), are
      widely used as insecticides and pesticides and may be stored as biological
      weapons. The massive use of these products, along with a lack of personal
      protective equipment on the job, and accidental and intentional ingestions, has
      produced a great number of poisonings in farmers. A large part of the employment
      and income in southeastern Spain is concentrated in intensive greenhouse
      agriculture in which growers are exposed to a varying degree of subsymptomatic
      doses of a combination of pesticides, mainly OPs and carbamates. We conducted a
      cross-sectional survey of workers in high-exposure conditions to assess possible
      neurobehavioral deficits, using a wide array of tasks to test neuropsychological
      functioning and emotional status. Linear and logistic regression series revealed
      the importance of the variable "years working with pesticides" as a measure of
      cumulative exposure for risk of worsened perceptive function performance (odds
      ratio (OR)=6.93, 95% confidence interval (CI): 1.52-31.51), visuomotor praxis
      (OR=5.00, 95% CI: 1.22-20.40) and integrative task performance time (OR=4.12, 95%
      CI: 1.18-14.39) with no relation to plasma cholinesterase activity as a measure
      of recent exposure. This association was statistically significant after
      controlling for confounds (age and educational level). The findings showed
      association of long-term exposure and worse performance in neuropsychological
      functions, which is interpreted as evidence of a chronic effect of cumulative
      high exposure to OPs and carbamates.

PMID- 15734276
TI  - Neuromotor functions in Inuit preschool children exposed to Pb, PCBs, and Hg.
AB  - The aim of this study was to examine the effects of prenatal and postnatal
      chronic exposure to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb)
      on the neuromotor development of preschool children. The study population
      consisted of 110 preschool Inuit children from Nunavik (Canada). Blood Hg, PCBs
      and Pb concentrations were measured at birth (cord blood) and at the time of
      testing. Gross motor functions were evaluated and a neurological examination was
      performed. Fine neuromotor performance was assessed using quantitative measures
      of postural hand tremor, reaction time, sway oscillations, as well as alternating
      and pointing movements. Potential covariates were documented including
      demographic and familial characteristics, other prenatal neurotoxicants (alcohol,
      tobacco) and nutrients (selenium (Se), Omega-3 polyunsaturated fatty acids (n-3
      PUFA)). Hierarchical multivariate regression analyses were performed, controlling
      for significant covariates. Gross motor development was not linked to prenatal
      exposures. However, significant associations were observed between blood Pb
      concentration at testing time and changes in reaction time, sway oscillations,
      alternating arm movements and action tremor. For some of these outcomes,
      neuromotor effects of Pb exposure are observed at blood concentrations below 10
      microg/dl. Negative effects of PCBs on neuromotor development were not clearly
      observed, neither were the potential beneficial effects of n-3 PUFA and selenium.
      Tremor amplitude was related to blood Hg concentrations at testing time, which
      corroborate an effect already reported among adults.

PMID- 15734278
TI  - Effects of prenatal cigarette and marijuana exposure on drug use among offspring.
AB  - The present study investigated whether maternal cigarette smoking and marijuana
      use during pregnancy were associated with an increased risk of initiation and
      daily/regular use of such substances among one hundred fifty-two 16- to 21-year
      old adolescent offspring. The participants were from a low risk, predominately
      middle-class sample participating in an ongoing, longitudinal study. Findings
      indicated that offspring whose mothers reported smoking cigarettes during their
      pregnancy were more than twice as likely to have initiated cigarette smoking
      during adolescence than offspring of mothers who reported no smoking while
      pregnant. Offspring of mothers who reported using marijuana during pregnancy were
      at increased risk for both subsequent initiation of cigarette smoking (OR=2.58)
      and marijuana use (OR=2.76), as well as daily cigarette smoking (OR=2.36), as
      compared to offspring of whose mothers did not report using marijuana while
      pregnant. There was also evidence indicating that dose-response relationships
      existed between prenatal exposure to marijuana and offspring's use of cigarettes
      and marijuana. These associations were found to be more pronounced for males than
      females, and remained after consideration of potential confounds. Such results
      suggest that maternal cigarette smoking and marijuana use during pregnancy are
      risk factors for later smoking and marijuana use among adolescent offspring, and
      add to the weight of evidence that can be used in support of programs aimed at
      drug use prevention and cessation among women during pregnancy.

PMID- 15734279
TI  - Absence of long-term behavioral effects after sub-chronic administration of low
      doses of methamidophos in male and female rats.
AB  - Putative long-term learning and memory effects of low-dose exposure to the
      cholinesterase inhibitor organophosphate methamidophos (Tamaron) early in life
      were studied in two parallel studies in middle-aged rats. Methamidophos was
      administered via the drinking water to female and male Wistar rats using nominal
      concentrations of 0 (control), 0.5, 1.5 and 4.5 ppm active ingredient for 16
      weeks. Animals were then maintained for a recovery period of about 14 months
      without treatment. They were tested in the standard and repeated acquisition
      version of the Morris water escape task in two series of tests starting 33 and 55
      weeks after termination of the methamidophos treatment. Functional observations
      and motor activity measurements preceded each series of testing. Exposure to
      methamidophos was confirmed by measurement of brain cholinesterase (ChE-B) at the
      end of the 16 weeks of treatment in satellite animals. At 4.5 ppm a biologically
      relevant reduction in ChE-B activity was observed without clinical signs of
      intoxication (males: 66%, females: 64% of control activity). Mid- and low-dose
      exposure to methamidophos revealed ChE-B activity of 90% and 100% in males and
      88% and 97% in females, respectively. General examinations of the animals during
      treatment revealed no clinical signs suggesting cholinergic stimulation.
      Functional observations and motor activity measurements exhibited no relevant
      differences between treatment groups and controls. Neither the performance in the
      standard Morris water escape task that predominantly measures spatial reference
      memory, nor in the repeated acquisition task in the Morris tank, which
      predominantly measures spatial working memory, was affected by treatment with
      methamidophos. A small number of statistically significant differences were noted
      in the mean performance level between treatment groups, or between treatment by
      sex groups in both versions of the Morris task. However, these findings appeared
      to be idiosyncratic for a particular experiment and were not supported by
      findings from the other. They were consequently not considered as reflecting a
      consistent effect of methamidophos on learning and memory. In conclusion,
      administration of low doses of methamidophos to female and male Wistar rats for
      16 weeks during early adulthood did not impair spatial working and reference
      memory in the Morris water escape task 33 and 55 weeks after cessation of
      treatment.

PMID- 15734280
TI  - Permanent motor activity and learning disorders induced by exposure to phenytoin
      during gestation and early infancy in the rat.
AB  - Experimental models and clinical data indicate that the incidence of motor and
      learning disorders may be increased in children of epileptic mothers taking
      phenytoin (PHT) during pregnancy. There is little data on the vulnerability of
      infants to PHT-induced long-term behavioral toxicity after gestational or early
      life exposure (i.e., infantile convulsion therapy). We examined the persistence
      of alterations in circling behavior induced by exposure to PHT during gestation,
      infancy, or both. Pregnant Sprague-Dawley rats were injected i.p. with saline
      (SAL) or PHT (30 mg/kg/day) during gestational days (GD) 10-18. The offspring
      were then administered (i.p.) SAL or PHT (60 mg/kg/day) during postnatal days
      (PD) 13-23. Afterward, Circling Training tests were performed at three time
      points. At PD40 and PD80, the clockwise direction of circling was reinforced. At
      PD150, counterclockwise circling was rewarded instead. At PD40, all PHT-treated
      groups demonstrated increased circling velocities compared to saline-treated
      controls. Higher spatial error rates for direction of circling were also observed
      in gestation-only and infancy-only exposures. At PD80, groups exposed during
      gestation had higher circling velocities than control or infancy-only exposed
      groups. At PD150, increases in circling velocity were apparent for the reverse
      learning task in groups exposed during gestation. These results indicate that
      early postnatal exposure to PHT may exacerbate the known long-term behavioral
      effects of gestational exposure.

PMID- 15734281
TI  - Volume, trend and citation analyses of skin related publications from 1966 to
      2003.
AB  - Research activities in the field of dermatology and skin biology have markedly
      improved our understanding of the physiology of skin and pathogenic mechanisms of
      cutaneous diseases. To evaluate the progress of such activities in a
      retrospective manner, we extracted more than 250,000 skin-related publications
      between 1966 and 2002 from the MEDLINE database and categorized them on the basis
      of the topics and experimental approaches. We observed that the annual number of
      publications in skin research had increased comparably with publications in lung
      or kidney research, and we identified several notable changes in research trends.
      To assess the impact of skin research on the biomedical community as a whole, we
      extracted from the PubMed database in excess of 3200 skin-related articles
      published between 1975 and 2003 in 19 highly ranked journals with impact factors
      greater than 10.0. Interestingly, two major research areas, immunology and
      cancer, appeared to dominate both clinical and basic science articles published
      in those top tier journals. From this collection of publications, we generated a
      list of the top 101 skin-related articles based on the citation numbers. Not only
      does our survey highlight past accomplishments, it also provides an important
      clue for predicting the future direction of skin research.

PMID- 15734282
TI  - Tempol, one of nitroxides, is a novel ultraviolet-A1 radiation protector for
      human dermal fibroblasts.
AB  - BACKGROUND: Nitroxide has been reported to have antioxidant and some
      photoprotective properties. Exposure of skin to ultraviolet-A1 (UVA1, 340-400 nm)
      can lead to formation of reactive oxygen species, reduction in collagen, and
      increased expression of matrix metalloproteinases (MMPs). OBJECTIVE: The goal of
      this research was to determine the effects of 4-hydroxy-Tempo (Tempol), one of
      nitroxides, in the presence of UVA1 on cytotoxicity, superoxide dismutase enzyme
      (SOD) activity, lipid peroxidation, and expression of collagen I, collagen III
      and MMP-1, MMP-3 in human dermal fibroblasts in vitro. METHODS: Fibroblasts were
      irradiated by a single exposure to UVA1 and at the same time incubated with, or
      without, Tempol and detected twenty-four hours later. SOD activity and lipid
      peroxidation, as shown by accumulation malonyldialdehyde (MDA), were detected by
      biochemical assay. Expressions of collagen I, collagen III (protein levels) and
      MMP-1, MMP-3 (mRNA level) were detected by ELISA and semi-quantitative reverse
      transcriptase-PCR separately. RESULTS: Cell survival curve after UVA1 irradiation
      showed dose dependent decrement pattern and Tempol, between 0.03 and 8 mM,
      increased cell viability in a dose-effect manner when the cells were exposed to
      20 J/cm(2) UVA1. Fifteen Joule per centimetre square of UVA1 significantly
      inhibited SOD activity and collagen I, collagen III protein levels, while
      increased MDA level and stimulated MMP-1 and MMP-3 mRNA expression. Tempol
      reversed these effects caused by UVA1 in some degree or completely and in proper
      concentration, the results were statistically significant compared with
      irradiated group. CONCLUSIONS: Tempol had photoprotective properties against UVA1
      irradiation in vitro. With antioxidant ability, Tempol inhibited extracellular
      matrix degradation and preserved collagen production in dermis and may be used as
      an anti-photoaging agent.

PMID- 15734283
TI  - Correlation of clinical severity and ELISA indices for the NC16A domain of BP180
      measured using BP180 ELISA kit in bullous pemphigoid.
AB  - BACKGROUND: Titres of circulating autoantibodies detected by indirect
      immunofluorescence (IIF) have been used for the diagnosis and evaluation of
      disease activity in bullous pemphigoid (BP). In BP, the major pathogenic epitope
      is known to be the non-collagenous extracellular domain (NC16A) of the 180-kDa
      transmembrane hemidesmosomal protein (BPAG2). Recently, an enzyme-linked
      immunosorbent assay (ELISA) kit using the NC16A domain recombinant protein (BP180
      ELISA kit) has become commercially available to measure the quantities of
      pathogenic autoantibodies circulating in BP patients. OBJECTIVE: To investigate
      the correlation of clinical severity and ELISA indices in BP. METHODS: Fourteen
      patients with a typical form of BP and one refractory BP patient who died despite
      extensive treatment were included in this study. Antibody titres in sera from
      these patients were measured using BP180 ELISA kit and an analysis of ELISA
      indices with disease activity was performed. RESULTS: ELISA indices were
      significantly reduced after successful therapy, although IIF titres did not
      always show apparent correlations. In the patient with refractory BP, ELISA
      indices also showed a good correlation with disease course. ELISA indices
      measured using the BP180 ELISA kit were well correlated with the disease
      activity. CONCLUSION: This commercially available kit more closely followed
      disease activities than the IIF titres. The BP ELISA system may be a useful tool
      to evaluate the disease activity and to assess the effectiveness of the treatment
      of BP.

PMID- 15734284
TI  - Differentiation-specific localization of catalase and hydrogen peroxide, and
      their alterations in rat skin exposed to ultraviolet B rays.
AB  - BACKGROUND: It is now well known that to counteract oxidative stress and maintain
      a redox balance within the cells, the skin is equipped with a network of
      antioxidant enzymes. Among these enzymes, SOD and CAT are the major antioxidant
      enzymes protecting the epidermis. OBJECTIVE: In the present study, we have
      attempted to demonstrate the distribution of endogenous H(2)O(2) and the
      expression of CAT in the epidermis of newborn rats, in relation to epidermal
      differentiation, and alterations after UVB irradiation. METHODS: We have
      localized the antioxidant enzyme catalase (CAT) using immunohistochemical
      analysis, and hydrogen peroxide (H(2)O(2)) using in situ H(2)O(2) assay. RESULTS:
      We demonstrated that keratinocytes in the stratum granulosum produced H(2)O(2),
      and CAT was mainly expressed in the cytoplasm of cells from the stratum
      granulosum to the lower corneum, and in the cell periphery in the stratum
      granulosum of newborn rat skin. The results suggested that generation of H(2)O(2)
      and expression of CAT were coordinated and were indicative of epidermal
      differentiation as well as of the role of CAT in repairing redox damage by
      discomposing H(2)O(2). When rat skin was exposed to 50 mJ/cm(2) of ultraviolet B
      (UVB) rays, the accumulation of H(2)O(2) in the upper epidermis increased twenty
      four hours later, while CAT immunoreactivity decreased. CONCLUSION: The results
      suggested that generation of H(2)O(2) and expression of CAT were coordinated and
      were indicative of epidermal differentiation as well as of the role of CAT in
      repairing redox damage by discomposing H(2)O(2). In addition, UVB-induced
      oxidative stress in the present study seemed to alter the endogenous and
      differentiation-specific redox balance between H(2)O(2) and CAT.

PMID- 15734285
TI  - Analyses of a mouse model of the dermatitis caused by 2,4,6-trinitro-1
      chlorobenzene (TNCB)-repeated application.
AB  - BACKGROUND: The model of chronic dermatitis caused by repeated application of
      hapten is frequently used as a tool for assessment of the efficacy of a compound
      or the elucidation of chronic dermatitis. OBJECTIVE: The purpose of this study is
      to provide more detailed analysis of the model of chronic dermatitis caused by
      repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). METHODS: BALB/c
      mice were sensitized with TNCB on day -7 to the ear, and then TNCB was repeatedly
      applied to the same ear three times per week, through days 0-21. RESULTS: The
      repeated application of TNCB induced an increase of ear thickness, and a
      relatively steep increment of ear thickness from days 7 to 9 was observed. This
      increment reached almost a plateau at day 9. The peaks of ear swelling on days 7,
      14 and 21 were approximately two times higher than that on day 0. Regarding
      cytokines in the ear, the highest production of IL-1 beta, 4, 6 and 18 were
      observed on day 7. The peak production of IL-1 beta, 4 and 6 on day 7 was found
      within 24 h after the challenge, while that of IL-18 was found at 0 h. The
      inflammatory cell infiltration into epidermis and dermis was observed and
      increased in day 7, then reached almost a plateau on day 9. CONCLUSION: The
      indices such as thickness, swelling and inflammatory cell infiltration in the
      lesional skin was increased and maintained by repeated application, however, the
      protein levels of some cytokines were not always consistent with the reactions.

PMID- 15734286
TI  - Viability and adipogenic potential of human adipose tissue processed cell
      population obtained from pump-assisted and syringe-assisted liposuction.
AB  - BACKGROUND: Correcting soft tissue defects by autologous fat grafting has been a
      routine procedure in plastic surgery. Liposuction material for autologous fat
      grafting is normally obtained using a hand-held syringe. The pump-assisted
      liposuction technique is not used because of the belief that cells in the
      harvested fat tissue are necrotic from the physical forces created by the vacuum
      pump liposuction machine. OBJECTIVE: The metabolism and adipogenic potential of
      cultured mesenchymal precursor cells processed from pump and syringe
      lipoaspirates were studied. METHODS: Metabolic estimates were determined with
      alamarBlue assay. These cells were also induced along the adipogenic lineage with
      adipogenic induction factors. The extent of adipogenic differentiation was
      measured using a digital photo counting software. RESULTS: The cells obtained by
      pump-assisted liposuction are viable, have comparable metabolic activity and
      adipogenic potential which are comparable to cells using the syringe for
      aspiration. CONCLUSION: The implications of this study are that pump-assisted
      liposuction might be a possible alternative to aspirating adipose tissue for
      reimplantation during reconstruction procedures.

PMID- 15734287
TI  - The investigation on the skin whitening efficacy of Chinese herb extracts using
      the colour physics technology.

PMID- 15734288
TI  - Does the determination of the Bb vitamin D receptor genotype identify psoriasis
      vulgaris patients responsive to topical tacalcitol?

PMID- 15734289
TI  - Subclass distribution of type VII collagen-specific autoantibodies in patients
      with inflammatory bowel disease.

PMID- 15734290
TI  - Apoptosis-deficient Pro allele of p53 gene is associated with the resistance of
      psoriasis to the UV-based therapy.

PMID- 15734291
TI  - The effect of antibacterial peptide human beta-defensin-2 on interleukin-18
      secretion by keratinocytes.

PMID- 15734292
TI  - Ascorbic and 6-Br-ascorbic acid conjugates as a tool to increase the therapeutic
      effects of potentially central active drugs.
AB  - Ascorbic acid (AA) or 6-Br-ascorbate (BrAA) conjugation has been investigated as
      a tool to improve brain drug delivery by the Vitamin C transporter SVCT2. To this
      aim, the effects of AA- or BrAA-conjugation on drug affinity and uptake have been
      assessed in vitro, by using human retinal pigment epithelium (HRPE) cells, and
      compared in vivo on mice. Nipecotic, kynurenic and diclofenamic acids were chosen
      as model drugs. Kinetic and inhibition experiments referred to [(14)C]AA uptake
      into HRPE cells showed that nipecotic and kynurenic acids became able to interact
      with SVCT2, as competitive inhibitors, only when conjugated to AA or BrAA.
      Surprisingly, diclofenamic acid itself appeared able to interact with SVCT2, with
      an affinity that was significantly increased or decreased by AA or BrAA
      conjugation, respectively. HPLC analysis, performed on HRPE cells, confirmed the
      SVCT2 mediated transport for the BrAA-conjugate of nipecotic acid, whereas
      kynurenic acids conjugates although interacting with the transporter did not
      enter the cells. In accordance, only the nipecotic acid conjugates showed
      anticonvulsant activity after systemic injection in mice.

PMID- 15734293
TI  - Identification and quantitation of novel metabolites of amiodarone in plasma of
      treated patients.
AB  - In mammals, mono-N-desethylamiodarone (MDEA) is the only known metabolite of
      amiodarone. Our previous experiments demonstrated that in vitro MDEA may be
      hydroxylated, N-dealkylated, and deaminated. In this report, we investigated the
      concentration of these microsomal metabolites in the plasma of patients receiving
      amiodarone. The presence of the hydroxy-amiodarone and deiodinated amiodarone was
      also additionally investigated. A high-performance liquid chromatography
      atmospheric pressure chemical ionization tandem mass spectrometry (HPLC-APCI
      MS/MS) quantitative assay using morpholine-amiodarone as internal standard was
      developed for measuring these metabolites in the range of 3-250 ng ml(-1). In the
      concentration ranges 5-50 and 50-250 ng ml(-1), the coefficients of variation of
      the measurements were less than 14 and 7%, respectively. The concentrations of
      investigated compounds in plasma of patients (n=14) receiving amiodarone (0.2 g
      day(-1), orally for >2 months) varied inter-individually and were 140.0+/-85.2,
      39.1+/-20.8, and 26.2+/-15.2 ng ml(-1) for 3'OH-mono-N-desethylamiodarone, di-N
      desethylamiodarone, and deaminated amiodarone, respectively. The concentrations
      of MDEA and amiodarone in these samples were 970+/-347 and 11163+/-435 ng ml(-1),
      respectively. In contrast, the studied compounds were not detectable in plasma
      samples from eight patients receiving amiodarone intravenously. Qualitatively, in
      the plasma of patients receiving amiodarone orally, hydroxylated amiodarone was
      also positively detected by assaying the [M+H](+) ions at m/z 662, but the deiodo
      metabolites of amiodarone were not detected using mass spectrometry. Thus, in
      humans, amiodarone and MDEA were biotransformed by dealkylation, hydroxylation,
      and deamination.

PMID- 15734294
TI  - Antiprotozoal activities of new bicyclo[2.2.2]octan-2-imines and esters of
      bicyclo[2.2.2]octan-2-ols.
AB  - Several bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols were
      prepared. Their antitrypanosomal and antiplasmodial activities against
      Trypanosoma brucei rhodesiense (STIB 900) and the K1 strain of Plasmodium
      falciparum (resistant to chloroquine and pyrimethamine) were determined using
      microplate assays. Two of the synthesized bicyclo[2.2.2]octan-2-one 4'
      phenylthiosemicarbazones showed the highest antitrypanosomal activity (IC(50)<0.3
      microM) of the so far prepared 4-amino-6,7-diarylbicyclo[2.2.2]octane
      derivatives, but they are distinctly less active than suramine (IC(50)=0.0075
      microM). Most of the 4'-phenylthiosemicarbazones and a single bicyclo[2.2.2]octan
      2-yl benzoate exhibit attractive antimalarial activity (IC(50)=0.23-0.72 microM).
      Two bicyclooctanone oximes are even as active as chloroquine (IC(50)=0.08-0.15
      microM, chloroquine: IC(50)=0.12 microM against sensitive strains).

PMID- 15734295
TI  - Selenocarbamates are effective superoxide anion scavengers in vitro.
AB  - We investigated the superoxide anion-scavenging effects of six selenocarbamates
      and four thiocarbamates, using a highly sensitive quantitative chemiluminescence
      method. At 333 nM, six selenocarbamates and four thiocarbamates scavenged in the
      range of 2.9-68.7% of O(2)*-. Se-methyl N-phenylselenocarbamate and Se-methyl N
      (4-methylphenyl)selenocarbamate exhibited the strongest superoxide anion
      scavenging activity among the Se-selenocarbamates. In contrast, the corresponding
      S-thiocarbamates had moderate inhibitory effect. The 50% inhibitory
      concentrations (IC(50)) of Se-methyl-N-phenylselenocarbamate and Se-methyl-N-(4
      methylphenyl)selenocarbamate were determined to be 140 nM and 162 nM,
      respectively. Thus, these compounds acted in vitro as effective and potentially
      useful O(2)*- scavengers.

PMID- 15734296
TI  - Effect of liquid volume and food intake on the absolute bioavailability of
      danazol, a poorly soluble drug.
AB  - The influence of liquid intake and a lipid-rich meal on the bioavailability of a
      lipophilic drug was investigated. Danazol was used as the model substance. In a
      randomized four-way crossover study eight healthy male volunteers received four
      different treatments with danazol at 2-week intervals following an overnight fast
      (one I.V. infusion and three oral treatments). The I.V. formulation contained
      50mg danazol solubilized in 40% hydroxypropyl-beta-cyclodextrin. The oral
      treatments were a Standard treatment, a Standard + 800 ml water treatment and a
      Standard + lipid-rich meal treatment. The Standard oral treatment consisted of
      200 ml water and one capsule containing 100mg danazol, three 500 mg paracetamol
      tablets and two 500 mg sulfasalazine tablets. Paracetamol and sulfasalazine were
      used as markers for gastric emptying and small intestinal transit times. Intake
      of danazol with a lipid-rich meal or extra 800 ml water increased the
      bioavailability by 400 and 55%, respectively. Gastric emptying times increased in
      the following order: Standard<Standard + 800 ml water<Standard + lipid-rich meal.
      The effects of food and liquid on danazol bioavailability can at least partly be
      explained by a delay in the gastric emptying time.

PMID- 15734297
TI  - In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow
      through dissolution method with biorelevant dissolution media.
AB  - The purpose of the study was to design dissolution tests that were able to
      distinguish between the behaviour of danazol under fasted and fed conditions, by
      using biorelevant media. In vitro dissolution of 100mg danazol capsules was
      performed using the flow-through dissolution method. Flow rates were 8, 16 or 32
      ml/min, corresponding to total volumes dissolution medium of 960, 1920 and 3840
      ml, respectively. The media used contained bile salt and phospholipid levels
      relevant for either fasted or fed conditions in vivo. Crude and inexpensive bile
      components, Porcine Bile Extract and soybean phospholipids, were used as the bile
      source. The effect of adding different concentrations and molar ratios of
      monoglycerides and fatty acids to the fed state media was investigated. In vivo
      release profiles under fasted and fed conditions were obtained from a previous
      study by deconvolution [Sunesen, V.H., Vedelsdal, R., Kristensen, H.G.,
      Christrup, L., Mullertz, A. 2005. Effect of liquid volume and food intake on the
      absolute bioavailability of danazol, a poorly soluble drug, Eur. J. Pharm. Sci.
      24, 297-303]. In the fasted state, the physiologically most relevant correlation
      with in vivo results was achieved with a medium containing 6.3 mM bile salts and
      1.25 mM phospholipids (8 ml/min). A medium containing 18.8 mM bile salts, 3.75 mM
      phospholipids, 4.0 mM monoglycerides and 30 mM fatty acids (8 ml/min) gave the
      closest correlation with fed state in vivo results. By using the flow-through
      dissolution method it was possible to obtain correlations with in vivo release of
      danazol under fasted and fed conditions. Both hydrodynamics and medium
      composition were important for the dissolution of danazol. In the fed state an
      IVIVC could only be obtained by including monoglycerides and fatty acids in the
      medium.

PMID- 15734298
TI  - A new amino-masking group capable of pH-triggered amino-drug release.
AB  - The prodrug approach is potentially useful for mitigating pharmaceutical problems
      -such as poor membrane permeability or stability--which commonly occur with amino
      drugs. On the other hand there persists a dearth of useful systems for masking
      amines that satisfy the prodrug requirements of good in vitro stability coupled
      with predictable and rapid drug release in response to a local tissue condition.
      This study describes an evaluation of aminoindanes as bioreversibly masked amines
      poised to undergo elimination to the parent amine. Several model amine and amino
      drug indanone derivatives were synthesised. pK(a) values were determined by
      capillary electrophoresis and pH rate profiles for elimination and amine
      liberation were measured. The aminoindanone system appears to have particular
      applicability to secondary amino substrates whose indanone derivatives are stable
      at low pH but undergo drug release at rates corresponding to first-order half
      lives of <5 min at pH 7.4.

PMID- 15734299
TI  - Influence of flow rate on the disposition of levofloxacin and netilmicin in the
      isolated rat lung.
AB  - The objective of this study was to examine the influence of the rate at which the
      tissue is perfused on the disposition of levofloxacin and netilmicin in the
      pulmonary tissue, using an experimental model of the isolated rat lung. Analysis
      of the results was performed using two pharmacokinetic approaches. By stochastic
      analysis of outflow curves the corresponding statistical moments and derived
      distribution coefficient were calculated. Model-dependent analysis based on a
      three-compartment dispersion model was also applied to the outflow concentration
      data. A statistically significant decrease in the distribution coefficient was
      observed for both antibiotics when the flow rate was decreased. For levofloxacin
      this parameter takes values of 2.14 and 1.25 mL/g for 10 and 5 mL/min flow rates,
      respectively. In the case of netilmicin these values were 0.81 and 0.39 mL/g for
      the higher and lower flow rates, respectively. Model parameters related to the
      distribution process were also modified as a consequence of the flow rate
      decrease. Tissue flow rate seems to be a determinant factor on the distribution
      of levofloxacin and netilmicin in the isolated rat lung.

PMID- 15734300
TI  - Caco-2 permeability of weakly basic drugs predicted with the double-sink PAMPA
      pKa(flux) method.
AB  - The aim of this study was to analyze pH-dependent permeability of cationic drugs
      in Caco-2 cell monolayers using the pK(a)(flux) method and to correlate the
      results with those obtained in PAMPA (parallel artificial membrane permeability
      assay). The pH-dependent permeability of verapamil and propranolol was studied in
      Caco-2 cell monolayers. The data were subsequently processed using software
      developed for the PAMPA pK(a)(flux) method. Literature values for an additional
      nine cationic drugs were also analyzed. Double-Sink PAMPA data were also obtained
      for the same cationic drugs, to compare with the Caco-2 data. The Algorithm
      Builder program was then used to develop a predictive model of Caco-2
      permeability based on PAMPA permeability and calculated Abraham molecular
      descriptors. From the relationship between permeability and pH it was shown that
      in PAMPA only the uncharged form of the drugs permeated across the membrane
      barrier, while charged and ionized forms of the drugs were significantly
      permeable in Caco-2. The charged-form permeability, P(i), was therefore
      determined and subsequently subtracted from all permeability coefficients in Caco
      2 prior to the comparison with PAMPA. The resulting intrinsic permeability
      coefficients (P(o)) obtained in Caco-2 were successfully related to those derived
      from the PAMPA model. In this study we have shown that permeability coefficients
      obtained in PAMPA can predict the passive transcellular permeability in Caco-2.

PMID- 15734301
TI  - Correlation between the release characteristics of theophylline and the free
      volume of polyvinylpyrrolidone.
AB  - The purpose of this work was to study the drug-release properties of an amorphous
      polymer, polyvinylpyrrolidone applied conventionally as a binder in tablets. In
      order to gain data on the wearing properties of tablets, they were stored for a
      30 days period under different humidity conditions before the drug-release
      measurements. The active material chosen for the release study was theophylline.
      An exponential relationship was found, with good correlation, between the
      relative humidity of the storage medium and the mean dissolution time of
      theophylline from polyvinylpyrrolidone tablets and the size of free volume holes.
      Positron annihilation lifetime spectroscopy (PALS) measurements, performed
      parallel with the theophylline release study, showed that the main reason for
      this correlation is the rearrangement of the pore structure of PVP. The results
      suggest that the water-induced glassy to rubbery transition of the polymer plays
      a significant role in the drug-release characteristics.

PMID- 15734302
TI  - Fast-dissolving mucoadhesive microparticulate delivery system containing
      piroxicam.
AB  - We have studied the feasibility of preparing fast-dissolving mucoadhesive
      microparticulate delivery systems containing amorphous piroxicam to improve drug
      residence time on sublingual mucosa and drug dissolution rate. Two new
      mucoadhesive carriers, Eudragit L100 (EuLNa) and Eudragit S100 (EuSNa) sodium
      salts, both characterized by a fast intrinsic dissolution rate, have been
      selected. Microparticles containing piroxicam and EuLNa (series 1) or EuSNa
      (series 2) in ratios from 15/85 to 85/15% (m/m) were prepared by spray drying.
      The morphology and physical state of the microparticles and the effect of the
      microparticle composition on the piroxicam release and mucoadhesion were
      investigated. Piroxicam loaded into the microparticles was found to be in the
      amorphous form at all drug/copolymer ratios. This feature was ascribed to the
      presence of an H-bond between the NH of piroxicam and a CO of the copolymers. The
      formation of solid solutions improved the dissolution rate and the apparent drug
      solubility. The mucoadhesive properties were affected by the drug/copolymer ratio
      and in series 2 the microparticles containing more than 50% (m/m) of piroxicam
      did not show mucoadhesive properties. The delivery system made of piroxicam and
      EuLNa in the ratio 70/30% (m/m) appears to be the most promising because it
      contains the lowest amount of polymer able to confer mucoadhesive properties and
      increase apparent drug solubility.

PMID- 15734303
TI  - Emulsion gel beads of calcium pectinate capable of floating on the gastric fluid:
      effect of some additives, hardening agent or coating on release behavior of
      metronidazole.
AB  - Emulsion gel (EMG) beads of calcium pectinate capable of floating in the gastric
      condition were developed using an emulsion-gelation method and their release
      properties were investigated. Attempts to modify the drug release were made by
      applying some additives into the starting solution prior to bead formation, by
      hardening with glutaraldehyde, and by coating with polymer. The metronidazole
      loaded EMG beads were found to float on simulated gastric fluid. Increasing the
      drug to pectin ratio in the beads slowed the drug release from the conventional
      and the EMG beads. However, the drug release from these beads was rapid, i.e.,
      about 80% of drug loading released within 20-80 min. The additives (PEG10000,
      glyceryl monostearate and Eudragit L) had a slight, insignificant, effect on the
      drug release. Using 2% glutaraldehyde as a hardening agent prolonged the drug
      release. Coating the beads with Eudragit RL significantly sustained the drug
      release while the beads remained buoyant. The results suggest that EMG beads are
      suitable as a carrier for intragastric floating drug delivery and that their
      release behaviour could be modified by hardening with glutaraldehyde or by
      coating with Eudragit RL.

PMID- 15734304
TI  - Separation of aceclofenac and diclofenac in human plasma by free zone capillary
      electrophoresis using N-methyl-D-glucamine as an effective electrolyte additive.
AB  - Aceclofenac (A) and diclofenac (D) are effective non-steroidal anti-inflammatory
      drugs (NSAIDs) derived from the phenylacetic acid with pronounced antirheumatic,
      anti-inflammatory, analgesic and antipyretic properties. Our work proposes a new,
      fast-free zone capillary electrophoresis method for the simultaneous
      determination of aceclofenac and diclofenac in human plasma. The effect of
      increasing concentrations of N-methyl-D-glucamine organic base on borate run
      buffer was investigated. A good separation was achieved using a 40 cm x 75 microm
      uncoated silica capillary, 300 mmol/l sodium borate buffer, 200 mmol/l N-methyl-D
      glucamine, pH 8.9, in about 3 min. Moreover, the plasma sample pre-treatment
      procedure was examined: acidic precipitants such as trichloroacetic acid (TCA),
      metaphosphoric acid (MPA), perchloric acid (PCA) or 5-sulphosalicylic acid (SSA)
      cause a total loss of analytes while acetonitrile allows a recovery of 97-98% of
      both compounds. Its simplicity and rapidity and the low analysis costs
      demonstrate that our method is a reliable and efficient mean for the
      comprehensive determination of aceclofenac and diclofenac in human plasma when
      pharmacokinetics studies are required.

PMID- 15734305
TI  - Evaluation of a chylomicron flow blocking approach to investigate the intestinal
      lymphatic transport of lipophilic drugs.
AB  - The purpose of this study was to examine the feasibility of investigating the
      lymphatic transport of drugs in vivo utilizing known chylomicron flow blocking
      substances. Vitamin D(3) (0.5 mg/kg), a model lipophilic molecule, was
      administered to rats with blocked chylomicron flow, induced by either
      cycloheximide injection (3 mg/kg), colchicine injection (5 mg/kg) or
      intraduodenal infusion of pluronic L-81 (1 mg/h). The effect of these
      experimental models on the absorption of Vitamin D(3) was compared to the
      outcomes of the mesenteric lymph duct cannulated rat model. The oral d-xylose
      loading test was used to verify that other intestinal absorptive functions were
      not affected. Colchicine treatment induced severe adverse effects whereas
      pluronic L-81 and the cycloheximide models did not affect other absorption
      pathways and did not cause apparent adverse effects. Vitamin D(3) absorption in
      these two models was in good correlation to the mesenteric lymph duct cannulation
      model (25% non-lymphatic relative bioavailability) indicating that the
      incorporation of the lipophilic molecule into the chylomicron is an essential
      step in the cascade of lymphatic absorption. Moreover, the data suggest that the
      drug association with the chylomicron occurs at an early stage of its assembly
      process. The results also specify that lymphatic absorption and portal blood
      absorption are separate pathways that are not affected by each other. In
      conclusion, the chemical blockage of chylomicron flow provides a potential
      approach for lymphatic transport investigation, and may elucidate processes
      involving in the absorption of lipophilic compounds.

PMID- 15734306
TI  - Microbial community analysis and performance of a phosphate-removing activated
      sludge.
AB  - The microbial community of a phosphate-removing activated sludge was analyzed
      according to the extracted 16S rDNA sequences. The sludge, which accumulated 5.6%
      P by weight, was obtained from a sequencing batch reactor treating a fatty-acid
      rich wastewater containing 108 mg l(-1) total organic carbon (TOC), 14.0 mg l(-1)
      N and 16.2 mg l(-1) P. The reactor at 25 degrees C and pH 7.6 removed over 96%
      TOC and 99.9% P from the wastewater. According to the 16S rDNA analysis of the
      114 clones developed, the sludge had a diverse population, mainly comprising
      Proteobacteria (71.0%) and the Cytophaga Flavobacterium Bacteroides group
      (23.7%), plus a few species of Planctomycetales (2.6%), Verrucomicrobiales (1.8%)
      and Firmicutes (0.9%). Of the 114 clones, 36 (31.6%) were closely affiliated with
      Acinetobacter. However, Acinetobacter did not accumulate phosphate judging from
      the images of sludge samples hybridized with an Acinetobacter-specific probe and
      stained with a phosphate-specific dye. The identities of the phosphate-removing
      bacteria remain unclear.

PMID- 15734307
TI  - Effect of molybdate on methanogenic and sulfidogenic activity of biomass.
AB  - The effect of molybdate, a sulfate analog, on the total methanogenic activity
      (TMA) and total sulfidogenic activity (TSA) of biomass metabolizing synthetic
      sucrose based substrate containing sulfate was investigated in batch assays. In
      Phase I of the study, TMA and TSA were assessed twice for four feed changes at a
      chemical oxygen demand to sulfate (COD/SO(4)(2-)) ratio of 3.5. In Phase II, long
      term experiments were conducted for 10-13 feed changes with varying chemical
      oxygen demand (COD) concentration, sulfate concentration, COD/SO(4)(2-) ratio,
      molybdate dose and biomass with different growth histories. Assays with 3mM
      molybdate showed TSA inhibition over 85%. Dose dependency was observed for
      sulfate concentration, COD/SO(4)(2-) ratio, and biomass history. The minimum
      concentration that gave over 93% TSA inhibition was 0.25 mM. However,
      intermediate concentrations of molybdate inhibited methane producing bacteria
      (MPB) activity. TMA stimulation was observed at 0.75-2.0 mM molybdate.

PMID- 15734308
TI  - Tamarind seed powder and palm kernel cake: two novel agro residues for the
      production of tannase under solid state fermentation by Aspergillus niger ATCC
      16620.
AB  - Palm kernel cake (PKC), the residue obtained after extraction of palm oil from
      oil palm seeds and tamarind seed powder (TSP) obtained after removing the fruit
      pulp from tamarind fruit pod were tested for the production of tannase under
      solid-state fermentation (SSF) using Aspergillus niger ATCC 16620. The fungal
      strain was grown on the substrates without any pretreatment. In PKC medium, a
      maximum enzyme yield of 13.03 IU/g dry substrate (gds) was obtained when SSF was
      carried out at 30 degrees C, 53.5% initial substrate moisture, 33 x 10(9)
      spores/5 g substrate inoculum size and 5% tannic acid as additional carbon source
      after 96 h of fermentation. In TSP medium, maximum tannase yield of 6.44 IU/gds
      was obtained at 30 degrees C, 65.75% initial substrate moisture, 11 x 10(9)
      spores/5 g substrate inoculum, 1% glycerol as additional carbon source and 1%
      potassium nitrate as additional nitrogen source after 120 h of fermentation.
      Results from the study are promising for the economic utilization and value
      addition of these important agro residues, which are abundantly available in many
      tropical and subtropical countries.

PMID- 15734309
TI  - Isolation of palm oil-utilising, polyhydroxyalkanoate (PHA)-producing bacteria by
      an enrichment technique.
AB  - In early attempts to isolate palm oil-utilising bacteria from palm oil mill
      effluent (POME), diluted liquid samples of POME were spread on agar containing
      POME as primary nutrient. 45 purified colonies were screened for intracellular
      lipids by staining with Sudan Black B. Of these, 10 isolates were positively
      stained. The latter were grown in a nitrogen-limiting medium with palm olein (a
      triglyceride) or saponified palm olein (salts of fatty acids) as carbon source.
      None of the isolates grew in the palm olein medium but all grew well in the
      saponified palm olein medium. Of the latter however, only one isolate was
      positively stained with Nile Blue A, indicating the presence of PHA. This method
      did not successfully generate bacterial isolates which could metabolise palm
      olein to produce PHA. An enrichment technique was therefore developed whereby a
      selective medium was designed. The latter comprised minerals and palm olein (1%
      w/v) as sole carbon source to which POME (2.5% v/v) was added as the source of
      bacteria. The culture was incubated with shaking at 30 degrees C for 4 weeks. Out
      of seven isolates obtained from the selective medium, two isolates, FLP1 and
      FLP2, could utilise palm olein for growth and production of the homopolyester,
      poly(3-hydroxybutyrate). FLP1 is gram-negative and is identified (BIOLOG) to have
      80% similarity to Burkholderia cepacia. When grown with propionate or valerate,
      FLP1 produced a copolyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate).

PMID- 15734310
TI  - Larvicidal activity of Tagetes patula essential oil against three mosquito
      species.
AB  - Larvicidal activity of Tagetes patula essential oil was tested against the fourth
      instar larvae of Aedes aegypti, Anopheles stephensi, and Culex quinquefaciatus.
      Five different concentrations of essential oil were studied and the results were
      compared with that of synthetic insecticide, malathion. A. aegypti (LC(50) 13.57,
      LC(90) 37.91) was most susceptible followed by An. stephensi (LC(50) 12.08,
      LC(90) 57.62) and C. quinquefaciatus (LC(50) 22.33, LC(90) 71.89).

PMID- 15734312
TI  - Conversion of bark-rich biomass mixture into fermentable sugar by two-stage
      dilute acid-catalyzed hydrolysis.
AB  - Despite high availability and low cost, bark has not actively been considered as
      a biomass feedstock for producing bio-based products due to its high content of
      extractives and lignin. In this study, to investigate the feasibility of
      utilizing bark-rich sawmill residues for producing value-added materials, the
      mixed Hemlock hog fuel/pin chips (85:15 by dry weight) from a local sawmill were
      converted into fermentable sugar by two-stage dilute sulfuric acid-catalyzed
      hydrolysis. Combining the sugar yields from the first-stage (190 degrees C for
      150 s with 1.1% acid) and second-stage (210 degrees C for 115 s with 2.5% acid)
      hydrolyses, which aimed to maximize the recovery of mannose/galactose and
      glucose, respectively, 13.6 g of glucose (46% theoretical maximum), 10.5 g of
      mannose and galactose (98% theoretical maximum), and 2.8 g of xylose (85%
      theoretical maximum) were obtained per 100 g of the original dry feedstock.

PMID- 15734311
TI  - Uranium removal from aqueous solution by coir pith: equilibrium and kinetic
      studies.
AB  - Basic aspects of uranium adsorption by coir pith have been investigated by batch
      equilibration. The influence of different experimental parameters such as final
      solution pH, adsorbent dosage, sorption time, temperature and various
      concentrations of uranium on uptake were evaluated. Maximum uranium adsorption
      was observed in the pH range 4.0-6.0. The Freundlich and Langmuir adsorption
      models were used for the mathematical description of the adsorption equilibrium.
      The equilibrium data fitted well to both the equilibrium models in the studied
      concentration range of uranium (200-800 mg/l) and temperatures (305-336 K). The
      coir pith exhibited the highest uptake capacity for uranium at 317 K, at the
      final solution pH value of 4.3 and at the initial uranium concentration of 800
      mg/l. The kinetics of the adsorption process followed a second-order adsorption.
      The adsorbent used proved to be suitable for removal of uranium from aqueous
      solutions. 0.2 N HCl was effective in uranium desorption. The results indicated
      that the naturally abundant coir pith of otherwise nuisance value exhibited
      considerable potential for application in removal of uranium from aqueous
      solution.

PMID- 15734313
TI  - Fractionation of wheat straw by atmospheric acetic acid process.
AB  - Fractionation of wheat straw was investigated using an atmospheric acetic acid
      process. Under the typical conditions of 90% (v/v) aqueous AcOH, 4% H(2)SO(4)
      (w/w, on straw), ratio of liquor to straw (L/S) 10 (v/w), pulping temperature 105
      degrees C, and pulping time 3h, wheat straw was fractionated to pulp (cellulose),
      lignin and monosaccharides mainly from hemicellulose with yields of approximately
      50%, 15% and 35%, respectively. Acetic acid pulp from the straw had an acceptable
      strength for paper and could be bleached to a high brightness over 85% with a
      short bleaching sequence. Acetic acid pulp was also a potential feedstock for
      fuels and chemicals. The acetic acid process separated pentose and hexose in
      wheat straw to a large extent. Most of the pentose (xylan) was dissolved, whereas
      the hexose (glucan) remained in the pulp. Approximately 30% of carbohydrates in
      wheat straw were hydrolyzed to monosaccharides during acetic acid pulping, of
      which xylose accounted for 70% and glucose for 12%. The acetic acid lignin from
      wheat straw showed relatively lower molecular weight and fusibility, which made
      the lignin a promising raw material for many products, such as adhesive and
      molded products.

PMID- 15734314
TI  - Immobilized white-rot fungal biodegradation of phenol and chlorinated phenol in
      trickling packed-bed reactors by employing sequencing batch operation.
AB  - The biodegradation of phenol and 2,4,6-trichlorophenol (2,4,6-TCP) by immobilized
      white-rot fungal cultures was studied in pinewood chip and foam glass bead-packed
      trickling reactors. The reactors were operated in sequencing batch format.
      Removal efficiency increased over time and elevated influent phenol and 2,4,6-TCP
      (800 and 85 mg l(-1)) concentrations were removed by greater than 98% in 24-30 h
      batch cycles. Comparable performance between the packing materials was shown.
      Increased lignin peroxidase (LiP) activity was detected with the introduction of
      the compounds and optimum activity corresponded to optimum removal periods.
      Higher LiP activity (16.7-19 Ul(-1)) was detected in glass bead-packed reactor
      compared to wood chip reactor (0.2-5 Ul(-1)). The presence of Mn(2+) in the wood
      material possibly effected elevated manganese peroxidase (MnP) activity (0.3-5.8
      Ul(-1)) compared to low to negligible activity in the glass bead reactor. Reactor
      performances are discussed in relation to sequencing batch operation and nutrient
      requirements necessary to induce and sustain fungal enzyme activity in inert vs.
      organic material packed systems.

PMID- 15734315
TI  - Autolytic degradation of chicken intestinal proteins.
AB  - Data on the exhaustive degradation of chicken intestinal proteins by endogenous
      proteases, which could be utilized as a means to prepare protein hydrolysate, is
      reported in the present paper. Chicken intestine possesses proteolytic activities
      (cathepsin B, D, H, L, aminopeptidases and alkaline proteases) comparable to that
      in organ tissues like liver and spleen, which could degrade the tissue proteins
      extensively. The autolytic degradation was found to be optimum at pH 2.5 and 60
      degrees C. Analysis by SDS-PAGE showed a time dependent degradation of proteins
      to low molecular weight (<10 kDa) products. Kinetic studies employing specific
      inhibitors indicated that the degradation (90-94%) of proteins at acidic pH is
      governed largely by pepstatin sensitive proteases. The acidic extract of the
      tissue was found to hydrolyse albumin, casein and soybean proteins efficiently.
      Results point to the possible application of tissue autolysis for obtaining
      protein hydrolysates from chicken intestine. Chicken intestine could also serve
      as a potential source of much needed proteolytic enzymes for food and
      pharmaceutical applications.

PMID- 15734316
TI  - Regression analysis for the sorption isotherms of basic dyes on sugarcane dust.
AB  - The sorption of three basic dyes, named basic violet 10, basic violet 1, and
      basic green 4, from aqueous solutions onto sugarcane dust was studied. The
      results revealed the potential of sugarcane dust, a waste material, to be a low
      cost sorbent. Equilibrium isotherms were analyzed using the Langmuir, the
      Freundlich, and the three-parameter Redlich-Peterson isotherms. In order to
      determine the best-fit isotherm for each system, two error analysis methods were
      used to evaluate the data: the linear coefficient of determination and the Chi
      square statistic test for determination of a non-linear model. Results indicated
      that the Chi-square test provided a better determination for the three sets of
      experimental data.

PMID- 15734317
TI  - Effect of pH on lead removal from water using tree fern as the sorbent.
AB  - The sorption of lead from water onto an agricultural by-product, tree fern, was
      examined as a function of pH. The sorption processes were carried out using an
      agitated and baffled system. Pseudo-second-order kinetic analyses were performed
      to determine the rate constant of sorption, the equilibrium sorption capacity,
      and the initial sorption rate. Application of the pseudo-second-order kinetics
      model produced very high coefficients of determination. Results showed the
      efficiency of tree fern as a sorbent for lead. The optimum pH for lead removal
      was between 4 and 7, with pH 4.9 resulting in better lead removal. Ion exchange
      occurred in the initial reaction period. In addition, a relation between the
      change in the solution hydrogen ion concentration and equilibrium capacity was
      developed and is presented.

PMID- 15734318
TI  - Effect of germination temperature on characteristics of phytase production from
      barley.
AB  - The effects of germination temperature on the growth of barley seedlings for
      phytase production were studied at 15, 20 and 25 degrees C for 6-10 days. The
      growth rate of the barley seedlings was increased as the germination temperature
      was increased. The initial rate of total protein production was closely coupled
      to that of the barley growth, and the rate of total protein production tended to
      increase as the germination temperature was increased. SDS-PAGE analysis of total
      protein from the barley seedlings showed time-dependent appearance and
      disappearance of protein bands. Although no significant phytase activity was
      detected at zero time of germination, a significant increase in phytase activity
      up to 7.9-fold occurred during the first several days of germination then
      decreased. Phosphate production (viz. phytate degradation) in the barley
      seedlings occurred rapidly at the beginning of germination. However, the rate of
      production continued to decrease with further germination. A time lag of about 1
      2 days between the rate of total protein production and that of phytase
      production was observed. Unlike the extent of total protein production, that of
      phytase production was similar irrespective of germination temperature. Partial
      purification of a crude enzyme extract by hydrophobic interaction chromatography
      resulted in two phytase fractions (PI and PII). Zymogram analysis demonstrated
      that PI had two bands with molecular masses of about 66 and 123 kDa while PII had
      one band corresponding to a molecular mass of about 96 kDa. The optimal
      temperature for PI was found to be 55 degrees C, while it was 50 degrees C for
      PII. The enzyme fraction PI had a pH optimum at 6.0, whereas the optimum pH for
      PII was found to be 5.0. Addition of 0.1% (v/v) Tween 80 was found to increase
      enzyme activity significantly (i.e., 167% for PI and 137% for PII). Phytate in
      cereals including barley, rice, corn and soybean degraded effectively by the
      treatment of the barley phytases.

PMID- 15734319
TI  - Accumulation of poly-beta-hydroxybutyrate in Nostoc muscorum: regulation by pH,
      light-dark cycles, N and P status and carbon sources.
AB  - Accumulation of poly-beta-hydroxybutyrate (PHB) in Nostoc muscorum was studied.
      Cells harvested at stationary phase of growth depicted maximum accumulation i.e.
      8.6% (w/w) of dry cells as compared to lag (4.1%) or logarithmic (6.1%) phases of
      cultures. In contrast to alkaline pH, acidic pH, continuous illumination and
      cells grown in presence of combined nitrogen sources, such as NH(4)Cl and KNO(3),
      were found to affect PHB accumulation negatively. However, P-deficiency and
      addition of exogenous carbon sources (acetate, glucose, maltose, fructose and
      ethanol) were found stimulatory for PHB accumulation. In this report PHB
      accumulation in N. muscorum was boosted up to 35% (w/w) of dry cells when cells
      supplemented with 0.2% acetate were subjected to dark incubation for 7 days.
      Further studies are needed at metabolic engineering level or to apply genetic
      engineering techniques to improve the expression level of PHB photoproduction in
      cyanobacteria.

PMID- 15734321
TI  - LCMS/MS and TOF-SIMS identification of the color bodies on the surface of a
      polymer.
AB  - The source of discoloration on a polymer surface can often be identified by
      washing the surface of the discolored polymer to collect the color bodies, then
      analyzing the washings using liquid chromatography-mass spectrometry (LCMS), with
      an in-line ultraviolet (UV) detector set at the optimum wavelength for the
      particular color bodies. A reference sample having no discoloration is also
      analyzed in the same way. In this paper, results from this methodology are
      compared with direct time of flight-secondary ion mass spectrometry (TOF-SIMS)
      analysis of a discolored polymer. The benefits and shortcomings of each
      methodology are discussed.

PMID- 15734320
TI  - Combined effect of alkali pretreatment and sodium chloride addition on the olive
      fermentation process.
AB  - Green olives of the Tunisian variety "Meski" were treated according to a Spanish
      style green olive preservation process by using an alkaline treatment (1.5, 2 and
      2.5% (w/v) NaOH) to eliminate bitterness, combined with different brine
      concentrations (6, 9 and 12% (w/v) NaCl). A spontaneous fermentation by the
      environmental microflora took place. Results showed that 2% NaOH solution and 9%
      sodium chloride brine was an optimal combination inducing the best growth of
      Lactobacillus species (10(8) CFU/ml) and acidity of 0.726 g lactic acid/100 ml
      brine. In all trials and independently of the treatment, Lb. plantarum was the
      most dominant strain of Lactobacillus. Moreover, pretreatment with lye and lactic
      fermentation of olives contributed to coliform elimination.

PMID- 15734322
TI  - ZoomQuant: an application for the quantitation of stable isotope labeled
      peptides.
AB  - The main goal of comparative proteomics is the quantitation of the differences in
      abundance of many proteins between two different biological samples in a single
      experiment. By differentially labeling the peptides from the two samples and
      combining them in a single analysis, relative ratios of protein abundance can be
      accurately determined. Protease catalyzed (18)O exchange is a simple method to
      differentially label peptides, but the lack of robust software tools to analyze
      the data from mass spectra of (18)O labeled peptides generated by common ion trap
      mass spectrometers has been a limitation. ZoomQuant is a stand-alone
      computational tool that analyzes the mass spectra of (18)O labeled peptides from
      ion trap instruments and determines relative abundance ratios between two
      samples. Starting with a filtered list of candidate peptides that have been
      successfully identified by Sequest, ZoomQuant analyzes the isotopic forms of the
      peptides using high-resolution zoom scan spectrum data. The theoretical isotope
      distribution is determined from the peptide sequence and is used to deconvolute
      the peak areas associated with the unlabeled, partially labeled, and fully
      labeled species. The ratio between the labeled and unlabeled peptides is then
      calculated using several different methods. ZoomQuant's graphical user interface
      allows the user to view and adjust the parameters for peak calling and
      quantitation and select which peptides should contribute to the overall abundance
      ratio calculation. Finally, ZoomQuant generates a summary report of the relative
      abundance of the peptides identified in the two samples.

PMID- 15734323
TI  - Trap for MAbs: characterization of intact monoclonal antibodies using reversed
      phase HPLC on-line with ion-trap mass spectrometry.
AB  - For the first time, the characterization of intact 150-kDa monoclonal antibodies
      (MAbs) using a commercially available three-dimensional ion-trap mass
      spectrometer (IT-MS) is reported. The IT-MS analysis was performed on-line with
      reversed-phase high performance liquid chromatography (RP-HPLC) on a POROS column
      using a nontraditional solvent system of acetonitrile, isopropanol, ethanol, and
      water in formic acid. The operating parameters of the IT-MS were optimized by
      extending the mass range to m/z 4000 and elevating the tube lens offset voltage
      value to around -100 V. Mass accuracy better than 300 ppm (+/-40 Da) has been
      routinely achieved for these macromolecules. Multiple peaks 162 Da apart due to
      the hexose variants of the monoclonal IgG antibodies were partially resolved in
      mass spectra. Several commercial and chimeric antibodies have been investigated
      in this study.

PMID- 15734324
TI  - Investigation of electrospray ionization and electrostatic focusing devices using
      a three-dimensional electrospray current density profiler.
AB  - A novel instrument for profiling the current density of nanoelectrospray
      ionization plumes in three dimensions has been developed. A hemispherically
      shaped electrostatic lens at atmospheric pressure is found to be able to compress
      the space-charge in nano-ESI and increase the average current density in the
      plume to three times the nominal value. Ion transmission into a single-quadrupole
      mass spectrometer is found to roughly double using the electrostatic lens. Data
      also suggest that ion transmission into the first vacuum region for a skimmer
      type mass spectrometer interface using nano-ESI may be typically 40% or better
      with no special focusing device used.

PMID- 15734325
TI  - Structural characterization of sialic acid synthase by electrospray mass
      spectrometry--a tetrameric enzyme composed of dimeric dimers.
AB  - Sialic acid synthase (NeuB) encoded by the neuB gene catalyzes the condensation
      of N-acetylmannosamine and phospho(enol)pyruvate to form N-acetylneuraminic acid.
      The enzyme is essential for the biosynthesis of polysialic acid, a capsular sugar
      polymer functioning as a virulent factor and antiphagocytic barrier. This report
      demonstrates the first characterization on the quaternary structure of NeuB from
      Escherichia coli (EcNeuB) and Streptococcus agalactiae (SaNeuB) by nanoflow
      electrospray ionization mass spectrometry (ESI-MS). Under non-denaturing
      conditions, Tris buffer was observed to induce a higher ratio of tetramer/dimer
      of NeuB in the ESI mass spectra, providing supportive evidence for the existence
      of a "structurally-specific" tetramer. The instrument parameters were found to
      significantly affect the ratio of detected tetramer/dimer in ESI mass spectra.
      The harshest conditions, including high desolvation voltages and pressure in the
      collision cell, led to enhanced detection of the 160 kDa tetramer. The prevalence
      of dimeric form is likely the cause in loss of tetramer stability in gas-phase
      arising from insufficient collisional cooling, which implies an asymmetric
      assembly, possibly composed of dimeric dimers. Most interestingly, the hypothesis
      was further supported by chemical cross-linking of SaNeuB, in which the reaction
      of shorter linker yielded mainly the dimer whereas that of longer linker produced
      both dimer and tetramer. Furthermore, the ESI-MS analysis can reflect dramatic
      change of pH-dependent quaternary structure in association with enzyme activity,
      suggesting the tetrameric form may be the primary species responsible for the
      enzyme catalysis.

PMID- 15734326
TI  - Immobilized carbon nanotubes as matrix for MALDI-TOF-MS analysis: applications to
      neutral small carbohydrates.
AB  - In this work, we reported on the advantages of immobilized carbon nanotubes as a
      novel MALDI-matrix. Recently, carbon nanotubes have been reported to be an
      effective MALDI matrix for small molecules (Anal. Chem.2003, 75, 6191), as it can
      eliminate the interfering matrix peaks as well as form a web morphology to fully
      disperse the analyte and allow strong ultraviolet absorption for enhanced pulsed
      laser desorption and ionization. In our study, to overcome the problem that the
      carbon nanotube matrix may fly off from the target, a type of polyurethane
      adhesive, NIPPOLAN-DC-205, is introduced to immobilize carbon nanotubes on the
      target, which enables widespread application of carbon nanotubes as matrix for
      MALDI-MS analysis. At the same time, the properties of the carbon nanotubes as an
      efficient matrix remained after immobilization. The presence of NIPPOLAN-DC-205
      increases the time for analysis at a particular desorption spot by minimizing the
      time-consuming search for "hot spots" and facilitating experiments such as post
      source decay (PSD) which need longer-lasting signals. Moreover, NIPPOLAN-DC-205
      produces no interference peaks and can easily be cleaned with acetone. Fast
      evaporation technology may be used to enhance signal reproducibility in MALDI
      analysis using carbon nanotubes as matrix. Consequently, the applicability of the
      carbon nanotube as matrix for matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) analysis of low molecular mass analytes is highly
      improved. The feasibility of the method employing polyurethane is demonstrated by
      comparison of the results produced from the carbon nanotube matrix with and
      without immobilization. In addition, neutral small carbohydrates, which are
      difficult to be ionized normally, can be cationized with high efficiency by MALDI
      TOF-MS using the immobilized carbon nanotube matrix. The method was further
      applied to analyze peptides and detect urine glucose successfully.

PMID- 15734327
TI  - Enhanced detection of sulfated glycosylation sites in glycoproteins.
AB  - We demonstrate a method that enhances the mass spectral signal of mono- and
      disulfated glycopeptides, present in glycoproteins that contain many other
      nonsulfated glycoforms. This method utilizes the tripeptide Lys-Lys-Lys as an ion
      pairing reagent to complex selectively to sulfated species, and enhance their ion
      signal. The method is applied to the analysis of glycopeptides released from the
      enzymatic digestion of ovine luteinizing hormone. In this analysis, a disulfated
      glycopeptide is identified that was previously not detectable by MS assays, and a
      monosulfated glycoform, present at less than 1% abundance, is identified without
      any separation or enrichment of these species prior to analysis. In addition to
      enhancing the ion signal of sulfated glycopeptides, the ion-pairing technique is
      useful in obtaining structural information about the sulfated species.

PMID- 15734328
TI  - Comparison of experimental and calculated peak shapes for three cylindrical
      geometry FAIMS prototypes of differing electrode diameters.
AB  - High-field asymmetric waveform ion mobility spectrometry (FAIMS) separates ions
      at atmospheric pressure and room temperature based on the difference of the
      mobility of ions in strong electric fields and weak electric fields. This field
      dependent mobility of an ion is reflected in the compensation voltage (CV) at
      which the ion is transmitted through FAIMS, at a given asymmetric waveform
      dispersion voltage (DV). Experimental CV, relative peak ion intensity, and peak
      width data were compared for three FAIMS prototypes with concentric cylindrical
      electrodes having inner/outer electrode radii of: (1) 0.4/0.6 cm, (2) 0.8/1.0 cm,
      and (3) 1.2/1.4 cm. The annular analyzer space was 0.2 cm wide in each case. A
      finite-difference numerical computation method is described for evaluation of
      peak shapes and widths in a CV spectrum collected using cylindrical geometry
      FAIMS devices. Simulation of the radial distribution of the ion density in the
      FAIMS analyzer is based upon calculation of diffusion, electric fields, and the
      electric fields introduced by coulombic ion-ion repulsion. Excellent agreement
      between experimental and calculated peak shapes were obtained for electrodes of
      wide diameter and for ions transmitted at low CV.

PMID- 15734329
TI  - Automated nanospray using chip-based emitters for the quantitative analysis of
      pharmaceutical compounds.
AB  - An automated nanospray system based on chip technology (the NanoMate) was
      successfully interfaced to a modified Particle Discriminator Interface on a
      triple quadrupole mass spectrometer. A number of the interface parameters were
      optimized to improve the sampling efficiency for ions from the chip-based system.
      Analytical performance was assessed using a number of biochemicals as well as via
      a methodology for a pharmaceutical that passed validation as required by Good
      Laboratory Practices. Infusion analyses in flow rates <1 microL/min provided
      advantages in terms of throughput and sample consumption when compared to other
      methodologies based on liquid chromatography.

PMID- 15734330
TI  - Investigation of metal-oligonucleotide complexes by nanoelectrospray tandem mass
      spectrometry in the positive mode.
AB  - The formation and fragmentation of multiply metal-coordinated oligonucleotides
      was studied by nanoelectrospray tandem mass spectrometry in the positive ion
      mode. Fundamental aspects of the gas-phase behavior of metal-oligonucleotide
      complexes are revealed. The addition of transition metal ions, such as iron(II),
      iron(III), and zinc(II), leads to very stable metal-oligonucleotide complexes
      which show heavily altered fragmentation patterns in contrast to uncomplexed
      oligonucleotides. The site of metal ion complexation was located by collision
      induced dissociation (CID) experiments. It was found that all three metal ions
      investigated predominantly coordinate to the central phosphate groups of the
      oligonucleotides. Furthermore, it is demonstrated that the fragmentation of such
      complexes depends highly upon the metal ion complexed as well as on the sequence
      of the nucleobases in the oligonucleotide.

PMID- 15734331
TI  - Upper stability island of the quadrupole mass filter with amplitude modulation of
      the applied voltages.
AB  - Modulation of the voltages applied to a quadrupole mass filter (QMF), either RF
      or RF and DC, leads to splitting of the stability region into islands of
      stability. The ion optical properties, such as transmission, resolving power and
      peak tails of the first upper stability islands have been investigated by
      numerical simulation of ion trajectories. The dependence of the location of this
      island on the amplitude of the modulation and the parameter nu = omega/Omega =
      Q/P where omega is modulation frequency, Omega is main angular radio frequency,
      and Q and P are integers, is calculated in detail. Different methods of adjusting
      the QMF resolution are examined. It is found that operation at the upper and
      lower tips of the stability islands created by amplitude modulation of the RF
      voltage is preferred, because of the technical simplicity of this method and a
      reduction of the required separation time. Amplitude modulation improves the
      performance of a QMF constructed with round rods, in comparison to perfect
      quadrupole fields. For example, with amplitude modulation of the RF, to reach a
      resolution of R(0.1) = 1200 requires only about 75 RF cycles of ion motion in a
      quadrupole field created by round rods.

PMID- 15734332
TI  - Chemometric approaches in calibration experiments of trilinolenoylglycerol by
      liquid chromatography ion-trap mass spectrometry.
AB  - The article presents a comprehensive account of the application of chemometric
      approaches to determine the factors that influence the tri-alpha
      linolenoylglycerol (TALG) ammoniated adduct signal m/z 890.6 in an ion-trap mass
      spectrometer coupled to a liquid chromatograph and the estimation of different
      sources of errors involved in TALG calibration experiments. It was found that by
      using experimental design, the influence of the nebulizer pressure on the
      analytical signal is less pronounced than the influence of the drying gas flow
      and the chromatographic flow rate. The results revealed that without using tandem
      mass or atmospheric pressure chemical ionization, it is possible to fragment the
      TALG backbone and obtain the free alpha-linolenic acid by varying the drying gas
      flow and using an electrospray interface. The error decomposition approach
      revealed that the preparation error was 26 times higher than the instrumental
      error.

PMID- 15734333
TI  - Structural characterization and regiochemical differentiation of alpha
      cyanoethylindole isomers in the gas phase.
AB  - Mass spectrometry and tandem mass spectrometry techniques have been used to study
      the gas phase ion chemistry of isomeric alpha-cyanoethylindoles obtained by
      photochemical reactions. Both the fragmentation reactions occurring in the ion
      source, as well as metastable decompositions produced by the molecular and
      selected fragment ions, have allowed us to structurally characterize and
      differentiate each isomer from the others. The experiments, carried out also on
      deuterium labeled analogs, have shown the role exerted by the alpha-cyanoethyl
      substituent and by its position at the indolic ring on gas phase reactions that
      resulted to be distinctive and selective for each isomer. Ab initio theoretical
      calculations have been used to evaluate the stability and chemico-physical
      properties of different ion structures.

PMID- 15734334
TI  - Correction of accurate mass measurement for target compound verification by
      quadrupole time-of-flight mass spectrometry.
AB  - The aim of this work is to evaluate quadrupole/time-of-flight (QTOF) mass
      spectrometry for simultaneous measurement of accurate mass and quantification of
      a target by using a stable isotopically labeled internal standard. Mixtures of
      caffeine and (13)C(3)-caffeine (internal standard) at different concentration
      ratios were analyzed by capillary HPLC/QTOF. A calibration plot for
      quantification is linear over a factor of 20. Without invoking any correction
      scheme, the mass accuracy seriously degraded when the ratio of the mass standard
      to the test compound was not unity. The accuracy could be restored to
      approximately 2 ppm by using a quadratic function to correct the measured mass as
      a function of the measured signal ratio of target and internal calibrant.

PMID- 15734336
TI  - Identification of a new source of interference leached from polypropylene tubes
      in mass-selective analysis.
AB  - An interference leached from polypropylene tubes was identified to be a sulfoxide
      oxidative product of didodecyl 3,3'-thiodipropionate (DDTDP) that is used to
      prevent oxidative degradation of synthetic polymers. A sulfone oxidative product
      of DDTDP leached from the polypropylene tubes was also observed. The interfering
      compounds were isolated by LC and characterized using time-of-flight mass
      spectrometry and NMR. Authentic sulfoxide and sulfone products of DDTDP were also
      prepared by reacting DDTDP with hydrogen peroxide reaching an unequivocal
      structural assignment. In conclusion, when analytes of interest are solubilized
      in predominantly organic solvents and kept in polypropylene containers, the
      possibility of contamination from leached chemicals should be taken into account.

PMID- 15734337
TI  - Collision induced ion ejection in an FTICR trapped-ion cell.
AB  - A collision algorithm was used with SimIon to evaluate collision-mediated ion
      ejection mechanisms in the ICR MS experiment. These mechanisms were characterized
      based on kinetic energy, ion mass, applied trapping potential, and collision gas
      mass. It was found that there are three collision-based energy regimes for ion
      loss from a trapped-ion cell. The first region is characterized by low initial
      cyclotron kinetic energy, a radial ejection mode, and a very high collision ratio
      (>100 collisions per ejection). The second region is characterized by a medium to
      high initial cyclotron kinetic energy leading to axial ejection at low collision
      ratio (1 to 10 collisions per ejection). The third region is characterized by a
      high initial cyclotron kinetic energy, a radial ejection mode, and a collision
      ratio of unity. It was also determined that there is a radial cyclotron mode
      limit, approximately 40% of the cell radius, after which an ion is ejected after
      a single collision. This has important consequences on the damping of the FTICR
      signal, various cooling techniques, ion activation techniques, and the
      remeasurement experiment.

PMID- 15734335
TI  - Shifts in protein charge state distributions with varying redox reagents in
      nanoelectrospray triple quadrupole mass spectrometry.
AB  - The influence of a number of redox reagents on the charge state distribution in
      nanoelectrospray mass spectrometry was examined using cytochrome c and ubiquitin.
      The redox active species investigated were: 1,4-benzoquinone, quinhydrone,
      tetracyanoquinodimethane (TCNQ), hydroquinone, and ascorbic acid. The redox
      active species was mixed with the protein sample before injection into the
      nanoelectrospray emitter, and mass spectra were acquired using a triple
      quadrupole mass spectrometer. Under the same experimental conditions, the charge
      state distribution of cytochrome c was observed to shift from a weighted average
      charge state of 14.25 (in the absence of redox species) to 7.10 in the presence
      of 1,4-benzoquinone. When quinhydrone was mixed with cytochrome c, the charge
      state distribution of the protein also shifted to lower charge states (weighted
      average charge state = 9.43), indicative of less charge state reduction for
      quinhydrone than with 1,4-benzoquinone. Addition of the redox reagent had little
      effect on the conformation of cytochrome c, as indicated by far ultraviolet
      circular dichroism spectra. In contrast, the reagents TCNQ, hydroquinone, and
      ascorbic acid exhibited negligible effects on the observed charge state
      distribution of the protein. The differing results for these redox reagents can
      be rationalized in terms of the redox half reactions involving these species. The
      results observed with ubiquitin upon adding quinhydrone were analogous to those
      observed with cytochrome c.

PMID- 15734338
TI  - Ecological nuances in functional magnetic resonance imaging (fMRI): psychological
      stressors, posture, and hydrostatics.
AB  - Brain imaging techniques such as functional magnetic resonance imaging (fMRI)
      have forged an impressive link between psychology and neuroscience. Whereas most
      experiments in cognitive psychology require participants to perform while sitting
      upright in front of display devices, fMRI obliges participants to perform
      cognitive tasks while lying supine and motionless inside a narrow bore. In
      addition to introducing psychological and physical stressors, such as loud thumps
      and head restraints, fMRI procedures also alter brain hydrostatics. The
      ecological factors associated with current fMRI technology, such as supine
      posture, may skew cognitive processing and influence hemodynamic and
      electrophysiological measurements, especially in extreme age groups and
      pathological populations. Recognizing the central role of fMRI in unraveling the
      neural mechanisms of cognition, we outline ways to address these limitations.

PMID- 15734339
TI  - EEG source analysis and fMRI reveal two electrical sources in the fronto-parietal
      operculum during subepidermal finger stimulation.
AB  - Using functional magnetic resonance imaging (fMRI) and electroencephalographic
      (EEG) source dipole analysis in 10 normal subjects, two electrical source dipoles
      in the contralateral fronto-parietal operculum were identified during repetitive
      painful subepidermal stimulation of the right index finger. The anterior source
      dipole peaking at 79 +/- 8 ms (mean +/- SD) was located in the frontal operculum,
      and oriented tangentially toward the cortical surface. The posterior source
      dipole peaking at 118 +/- 12 ms was located in the upper bank of the Sylvian
      fissure corresponding to the second somatosensory cortex (S2). The orientations
      of the posterior source dipoles displayed large variability, but differed
      significantly (P < 0.05) from the orientations of the anterior source dipoles.
      Electrical sources and fMRI clusters were also observed in ipsilateral fronto
      parietal operculum. However, due to low signal-to-noise ratio of ipsilateral EEG
      sources in individual recordings, separation of sources into anterior and
      posterior clusters was not performed. Combined fMRI and source dipole EEG
      analysis of individual data suggests the presence of two distinct electrical
      sources in the fronto-parietal operculum participating in processing of
      somatosensory stimuli. The anterior region of the fronto-parietal operculum shows
      earlier peak activation than the posterior region.

PMID- 15734340
TI  - An information-processing model of three cortical regions: evidence in episodic
      memory retrieval.
AB  - ACT-R (Anderson, J.R., et al., 2003. An information-processing model of the BOLD
      response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241-261) relates
      the inferior dorso-lateral prefrontal cortex to a retrieval buffer that holds
      information retrieved from memory and the posterior parietal cortex to an
      imaginal buffer that holds problem representations. Because the number of changes
      in a problem representation is not necessarily correlated with retrieval
      difficulties, it is possible to dissociate prefrontal-parietal activations. In
      two fMRI experiments, we examined this dissociation using the fan effect
      paradigm. Experiment 1 compared a recognition task, in which representation
      requirement remains the same regardless of retrieval difficulty, with a recall
      task, in which both representation and retrieval loads increase with retrieval
      difficulty. In the recognition task, the prefrontal activation revealed a fan
      effect but not the parietal activation. In the recall task, both regions revealed
      fan effects. In Experiment 2, we compared visually presented stimuli and aurally
      presented stimuli using the recognition task. While only the prefrontal region
      revealed the fan effect, the activation patterns in the prefrontal and the
      parietal region did not differ by stimulus presentation modality. In general,
      these results provide support for the prefrontal-parietal dissociation in terms
      of retrieval and representation and the modality-independent nature of the
      information processed by these regions. Using ACT-R, we also provide
      computational models that explain patterns of fMRI responses in these two areas
      during recognition and recall.

PMID- 15734341
TI  - Is medial temporal lobe activation specific for encoding long-term memories?
AB  - Several neuroimaging studies have consistently demonstrated the critical
      involvement of prefrontal cortices and medial temporal lobes during long-term
      encoding. While the contribution of prefrontal lobes to working memory is well
      established, the role of the MTL structures remains controversial. To address
      this issue, we registered the neuromagnetic brain patterns of eight adult
      volunteers while they performed two working memory tasks (verbal and spatial)
      using magnetoencephalography (MEG). MEG recordings can provide real-time measures
      of brain activity, thus allowing detailed tracking of the time-course of brain
      activation during the encoding phase. We detected sustained and material-specific
      activity on the MTLs during the encoding phase of a working memory task, based on
      verbal and spatial information. Two peaks of activation were noted in the left
      MTL during word encoding in two non-consecutive time periods (500-600 ms and 700
      800 ms after stimulus onset). Right MTL laterality was found for encoding
      locations when we collapsed activity sources in a wider time period (400-800 ms).
      In addition, we provided the spatiotemporal profiles of what seems to be two
      different brain circuits specific for each type of material. Finally, following
      an emerging conceptualization of working memory, we hypothesized that encoding
      processes mediated by the MTL to long-term memory would also apply to working
      memory.

PMID- 15734343
TI  - Dissociating intentional learning from relative novelty responses in the medial
      temporal lobe.
AB  - The establishment of a role for medial temporal lobe (MTL) structures in episodic
      memory has led to an investigative focus on the specific contributions and
      interactions between constituent MTL regions, including the hippocampus and
      surrounding medial temporal cortices. By dissociating an intentional stimulus
      category learning condition from a passive viewing condition, we demonstrate,
      using fMRI, that novelty- and familiarity-driven responses in human anterior and
      posterior hippocampus, respectively, only occur during intentional learning. With
      increasing familiarity of stimulus-category associations, there is a shift in
      neuronal responses from anterior to posterior hippocampal regions. This
      anterior/posterior response gradient may reflect a weighting of functional
      hippocampal architecture related to encoding of novel and retrieval of familiar
      information. By contrast, perirhinal cortex is engaged by novel stimuli
      irrespective of task, highlighting this region as a component of a generic
      familiarity discrimination system. By introducing distinct stimulus types, we
      further demonstrate that these MTL responses are independent of stimulus
      complexity. Different patterns of activity for intentional learning vs. passive
      viewing indicate that intentional encoding/retrieval of stimulus-category
      associations and automatic novelty/familiarity assessment of stimuli are
      processed in anatomically dissociable neuronal ensembles within the MTL memory
      system.

PMID- 15734342
TI  - Association between lower P300 amplitude and smaller anterior cingulate cortex
      volume in patients with posttraumatic stress disorder: a study of victims of
      Tokyo subway sarin attack.
AB  - Previous investigations of auditory P300 event-related potentials have provided
      electrophysiological evidence for attentional problems in patients with
      posttraumatic stress disorder (PTSD). The present study sought to evaluate the
      relationship between P300 deficits and underlying brain morphological
      abnormalities in never-treated, comorbidity-free patients with PTSD following the
      Tokyo subway sarin attack. Out of 47 victims recruited, 8 victims with PTSD and
      13 victims without PTSD were identified. Correlational analyses were performed
      between auditory P300 amplitude at Pz electrode site elicited in an oddball task
      and anterior cingulate gray matter volume that was shown to be reduced in our
      previous study using voxel-based morphometry on magnetic resonance imaging.
      Victims with PTSD showed significantly lower amplitudes of P300 compared with
      victims without PTSD, and the lower P300 amplitudes at Pz were significantly
      associated with higher avoidance/numbing scores in the PTSD group. Furthermore,
      in the PTSD group only, the P300 amplitudes showed a trend toward significant
      positive correlation with voxel densities of the anterior cingulate cortex gray
      matter. These results provide the first evidence that electrophysiological
      deficits of controlled attention observed in patients with PTSD may be linked to
      underlying brain morphological abnormalities.

PMID- 15734345
TI  - Listening to talking faces: motor cortical activation during speech perception.
AB  - Neurophysiological research suggests that understanding the actions of others
      harnesses neural circuits that would be used to produce those actions directly.
      We used fMRI to examine brain areas active during language comprehension in which
      the speaker was seen and heard while talking (audiovisual) or heard but not seen
      (audio-alone) or when the speaker was seen talking with the audio track removed
      (video-alone). We found that audiovisual speech perception activated a network of
      brain regions that included cortical motor areas involved in planning and
      executing speech production and areas subserving proprioception related to speech
      production. These regions included the posterior part of the superior temporal
      gyrus and sulcus, the pars opercularis, premotor cortex, adjacent primary motor
      cortex, somatosensory cortex, and the cerebellum. Activity in premotor cortex and
      posterior superior temporal gyrus and sulcus was modulated by the amount of
      visually distinguishable phonemes in the stories. None of these regions was
      activated to the same extent in the audio- or video-alone conditions. These
      results suggest that integrating observed facial movements into the speech
      perception process involves a network of multimodal brain regions associated with
      speech production and that these areas contribute less to speech perception when
      only auditory signals are present. This distributed network could participate in
      recognition processing by interpreting visual information about mouth movements
      as phonetic information based on motor commands that could have generated those
      movements.

PMID- 15734344
TI  - Raloxifene exposure enhances brain activation during memory performance in
      healthy elderly males; its possible relevance to behavior.
AB  - Raloxifene is a selective estrogen receptor modulator (SERM) that is prescribed
      in females only, but its use in male subjects is increasingly considered. With a
      growing number of patients having potential benefit from raloxifene, the need for
      an assessment of its effects on brain function is growing. Effects of estrogens
      on brain function are very subtle and difficult to detect by neuropsychological
      assessment. Functional imaging techniques, however, have been relatively
      successful in detecting such changes. This study used functional magnetic
      resonance imaging (fMRI) to examine effects of raloxifene treatment on memory
      function. Healthy elderly males (n = 28; mean age 63.6 years, SD 2.4) were
      scanned during performance on a face encoding paradigm. Scans were made at
      baseline and after 3 months of treatment with either raloxifene (n = 14) or
      placebo (n = 14). Treatment effects were analyzed using mixed-effects statistical
      analysis (FSL). Activation during task performance involved bilateral parietal
      and prefrontal areas, anterior cingulate gyrus, and inferior prefrontal,
      occipital, and mediotemporal areas bilaterally. When compared to placebo,
      raloxifene treatment significantly enhanced activation in these structures (Z >
      3.1), except for mediotemporal areas. Task performance accuracy diminished in the
      placebo group (P = 0.02), but remained constant in the raloxifene group (P =
      0.60). In conclusion, raloxifene treatment enhanced brain activation in areas
      spanning a number of different cognitive domains, suggesting an effect on
      cortical arousal. Such effects may translate into small effects on behavior,
      including effects on attention and working memory performance, executive
      functions, verbal skills, and episodic memory. Further neuropsychological
      assessment is necessary to test the validity of these predictions.

PMID- 15734346
TI  - Tactile estimation of the roughness of gratings yields a graded response in the
      human brain: an fMRI study.
AB  - Human subjects can tactually estimate the magnitude of surface roughness.
      Although many psychophysical and neurophysiological experiments have elucidated
      the peripheral neural mechanisms that underlie tactile roughness estimation, the
      associated cortical mechanisms are not well understood. To identify the brain
      regions responsible for the tactile estimation of surface roughness, we used
      functional magnetic resonance imaging (fMRI). We utilized a combination of
      categorical (subtraction) and parametric factorial approaches wherein roughness
      was varied during both the task and its control. Fourteen human subjects
      performed a tactile roughness-estimation task and received the identical tactile
      stimulation without estimation (no-estimation task). The bilateral parietal
      operculum (PO), insula and right lateral prefrontal cortex showed roughness
      related activation. The bilateral PO and insula showed activation during the no
      estimation task, and hence might represent the sensory-based processing during
      roughness estimation. By contrast, the right prefrontal cortex is more related to
      the cognitive processing, as there was activation during the estimation task
      compared with the no-estimation task, but little activation was observed during
      the no-estimation task in comparison with rest. The lateral prefrontal area might
      play an important cognitive role in tactile estimation of surface roughness,
      whereas the PO and insula might be involved in the sensory processing that is
      important for estimating surface roughness.

PMID- 15734347
TI  - Extracellular diffusivity determines contribution of high-versus low-affinity
      receptors to neural signaling.
AB  - Diffusion-weighted magnetic resonance imaging detects physiological changes in
      the human brain by highlighting alterations in local diffusivity. However, the
      causal link between brain tissue diffusivity and neural activity is poorly
      understood. Synaptic physiology studies in vitro coupled with biophysical
      modeling have suggested that extracellular diffusion affects the spatial profile
      of receptor activation during synaptic discharges. Here, we attempt to address
      this issue more directly, by recording synaptic currents from individual cells in
      acute brain slices while reducing the bath medium diffusivity by 25-30% (measured
      with two-photon microscopy) using inert dextran molecules. We find that retarding
      extracellular diffusion increases the activation of high-affinity NMDA, but not
      low-affinity AMPA, receptors in response to remote, spontaneous or evoked,
      synaptic releases of the common excitatory neurotransmitter glutamate. The
      results suggest that variations in extracellular diffusivity could reflect an
      altered contribution of higher- versus lower-affinity receptor types to the
      network activity of synaptic circuits.

PMID- 15734348
TI  - Positive or negative blips? The effect of phase encoding scheme on susceptibility
      induced signal losses in EPI.
AB  - The observation of blood oxygenation level-dependent (BOLD) effect in functional
      magnetic resonance imaging (fMRI) studies is often hampered by the presence of
      magnetic field inhomogeneities. These are caused by abrupt changes in the
      magnetic susceptibility that typically occur near air/tissue interfaces and may
      result in substantial image distortions and signal losses. In this article, we
      investigate the effect of susceptibility-induced magnetic field inhomogeneities
      on the signal intensity (I) and the BOLD sensitivity (BS) for two different phase
      encoding schemes in blipped echo-planar imaging (EPI), which use either positive
      (EPIpos) or negative (EPIneg) phase gradient blips for stepping through k-space.
      Based on magnetic field maps, we generate computer simulations of I and BS for
      both phase encoding schemes and demonstrate good agreement with the experimental
      image intensities. We show that regions compromised by susceptibility effects are
      affected very differently by EPIpos and EPIneg. Further simulations are performed
      in two representative regions of interest (orbitofrontal cortex and lower
      temporal lobe) to investigate the dependence of I and BS on the slice angle
      (alpha), the magnitude of a moderate compensation gradient applied in the slice
      direction (GScomp), and the phase encoding scheme. We find that I and BS can be
      considerably increased if the appropriate phase encoding scheme is applied in
      addition to optimizing alpha and GScomp. Our results suggest that this
      optimization method would be useful in future fMRI studies to improve the
      sensitivity in regions compromised by susceptibility effects.

PMID- 15734349
TI  - CASL fMRI of subcortico-cortical perfusion changes during memory-guided finger
      sequences.
AB  - Arterial spin labeling (ASL) perfusion functional magnetic resonance imaging
      (fMRI) is an attractive alternative to BOLD fMRI. Nevertheless, current ASL fMRI
      techniques are limited by several factors that hamper more routine applications
      in humans. One of these factors is restricted brain coverage so that whole-brain
      ASL fMRI studies have never been reported. The present study tested the ability
      of a multislice continuous ASL (CASL) fMRI approach using a small surface coil
      placed on the subject's neck to map changes in regional cerebral blood flow
      (rCBF) throughout the brain while healthy individuals (N = 15) performed memory
      guided sequential finger movements at a mean rate of approximately 0.5 Hz. As
      predicted by results from a large number of studies, reliable task-related
      increases in flow were detected across subjects not only in primary and
      associative cortical areas but also in subcortical brain regions. When normalized
      to baseline, rCBF increased 31% in the hand representation area (HRA) of left
      primary motor cortex (M1), 13% in the left supplementary motor area proper (SMA),
      10% in the left dorsolateral prefrontal cortex (DLPFC), 10-18% in the bilateral
      intraparietal sulci, 6% in the HRA of left putamen, 10% in the left thalamus, and
      17% in the right anterior cerebellum. In addition to these increases, 6% and 4%
      decreases in rCBF were detected in the HRA of the right M1 and the bilateral
      posterior cingulate sulci, respectively. These results demonstrate that perfusion
      based fMRI using CASL with a separate labeling coil can now be used to
      characterize task-related flow changes in most of the brain volume with adequate
      accuracy and sensitivity.

PMID- 15734350
TI  - An fMRI study of joint attention experience.
AB  - Although much is now known about eye movement detection, little is known about
      the higher cognitive processes involved in joint attention. We developed video
      stimuli which when watched, engender an experience of joint attention in the
      observer. This allowed us to compare an experience of joint attention to nonjoint
      attention within an fMRI scanning environment. Joint attention was associated
      with activity in the ventromedial frontal cortex, the left superior frontal gyrus
      (BA10), cingulate cortex, and caudate nuclei. The ventromedial frontal cortex has
      been consistently shown to be activated during mental state attribution tasks.
      BA10 may serve a cognitive integration function, which in this case seems to
      utilize a perception-action matching process. The activation we identified in
      BA10 overlaps with a location of increased grey matter density that we recently
      found to be associated with autistic spectrum disorder. This study therefore
      constitutes evidence that the neural substrate of joint attention also serves a
      mentalizing function. The developmental failure of this substrate in the left
      anterior frontal lobe may be important in the etiology of autistic spectrum
      disorder.

PMID- 15734351
TI  - Fractional Gaussian noise, functional MRI and Alzheimer's disease.
AB  - Fractional Gaussian noise (fGn) provides a parsimonious model for stationary
      increments of a self-similar process parameterised by the Hurst exponent, H, and
      variance, sigma2. Fractional Gaussian noise with H < 0.5 demonstrates negatively
      autocorrelated or antipersistent behaviour; fGn with H > 0.5 demonstrates 1/f,
      long memory or persistent behaviour; and the special case of fGn with H = 0.5
      corresponds to classical Gaussian white noise. We comparatively evaluate four
      possible estimators of fGn parameters, one method implemented in the time domain
      and three in the wavelet domain. We show that a wavelet-based maximum likelihood
      (ML) estimator yields the most efficient estimates of H and sigma2 in simulated
      fGn with 0 < H < 1. Applying this estimator to fMRI data acquired in the
      "resting" state from healthy young and older volunteers, we show empirically that
      fGn provides an accommodating model for diverse species of fMRI noise, assuming
      adequate preprocessing to correct effects of head movement, and that voxels with
      H > 0.5 tend to be concentrated in cortex whereas voxels with H < 0.5 are more
      frequently located in ventricles and sulcal CSF. The wavelet-ML estimator can be
      generalised to estimate the parameter vector beta for general linear modelling
      (GLM) of a physiological response to experimental stimulation and we demonstrate
      nominal type I error control in multiple testing of beta, divided by its standard
      error, in simulated and biological data under the null hypothesis beta = 0. We
      illustrate these methods principally by showing that there are significant
      differences between patients with early Alzheimer's disease (AD) and age-matched
      comparison subjects in the persistence of fGn in the medial and lateral temporal
      lobes, insula, dorsal cingulate/medial premotor cortex, and left pre- and
      postcentral gyrus: patients with AD had greater persistence of resting fMRI noise
      (larger H) in these regions. Comparable abnormalities in the AD patients were
      also identified by a permutation test of local differences in the first-order
      autoregression AR(1) coefficient, which was significantly more positive in
      patients. However, we found that the Hurst exponent provided a more sensitive
      metric than the AR(1) coefficient to detect these differences, perhaps because
      neurophysiological changes in early AD are naturally better described in terms of
      abnormal salience of long memory dynamics than a change in the strength of
      association between immediately consecutive time points. We conclude that
      parsimonious mapping of fMRI noise properties in terms of fGn parameters
      efficiently estimated in the wavelet domain is feasible and can enhance insight
      into the pathophysiology of Alzheimer's disease.

PMID- 15734352
TI  - Wavelet variance components in image space for spatiotemporal neuroimaging data.
AB  - Neuroimaging studies place great emphasis on not only the estimation but also the
      standard error estimates of underlying parameters derived from a temporal model.
      This allows inferences to be made about the signal estimates and resulting
      conclusions to be drawn about the underlying data. It can often be advantageous
      to interrogate temporal models after spatial transformation of the data into the
      wavelet domain. Wavelet bases provide a multiresolution decomposition of the
      spatial data dimension and an ensuing reduction in spatial correlation. However,
      widespread acceptance of these wavelet techniques has been hampered by the
      limited ability to reconstruct both parametric and error estimates into the image
      domain after analysis of temporal models in the wavelet domain. This paper
      introduces a derivation and a fast implementation of a method for the calculation
      of the variance of the parametric images obtained from wavelet filters. The
      technique is proposed for a class of estimators that have been shown to be useful
      in neuroimaging studies. The techniques are demonstrated for both functional
      magnetic resonance imaging (fMRI) and positron emission tomography (PET) data
      sets.

PMID- 15734353
TI  - Volumetric, connective, and morphologic changes in the brains of children with
      chromosome 22q11.2 deletion syndrome: an integrative study.
AB  - Chromosome 22q11.2 deletion syndrome is a highly prevalent genetic disorder whose
      manifestations include developmental disability and sometimes mental retardation.
      The few studies that have examined brain morphology in different samples from
      this population have found similar general patterns, mostly using region of
      interest measures. We employed voxel-based techniques to concurrently examine
      specific morphologic changes in multiple brain tissue measures. Results were
      similar to previous findings of volumetric reductions in the posterior brain.
      They also extended them in two ways. First, our methods provided greater
      specificity in the localization of changes detected. Second, the combination of
      our measures of gray and white matter along with cerebrospinal fluid volume and
      fractional anisotropy, which indicates the structure of white matter, showed a
      posterior displacement of and morphologic changes to the corpus callosum in
      affected children.

PMID- 15734354
TI  - Independent component analysis applied to self-paced functional MR imaging
      paradigms.
AB  - Self-paced functional MR imaging (fMRI) paradigms, in which the task timing is
      determined by the subject's performance, can offer several advantages over
      commonly applied paradigms with predetermined stimulus timing. Independent
      component analysis (ICA) does not require specification of a timed response
      function, and could be an advantageous method of deriving results from fMRI data
      sets with varying response timings and durations. In this study normal volunteers
      (N = 10) each performed two self-paced fMRI motor and arithmetic paradigms.
      Individual data sets were analyzed with the Infomax spatial ICA algorithm.
      Conventional regression analysis was performed for comparison purposes. Spatial
      ICA effectively produced task-related components from each of the self-paced data
      sets, even in a few cases where regression analysis yielded non-specific
      functional maps. For the motor paradigm, these components consistently mapped to
      primary motor areas. ICA of the arithmetic paradigm yielded multiple task-related
      components that variably mapped to regions of parietal and frontal lobes.
      Regression analysis generally yielded similar spatial maps. The multiple task
      related ICA components that were sometimes produced from each self-paced data set
      can be challenging to identify and evaluate for significance. These preliminary
      results indicate that ICA is useful as an exploratory and complementary method to
      conventional regression analysis for fMRI of self-paced paradigms.

PMID- 15734355
TI  - Independent component analysis of fMRI group studies by self-organizing
      clustering.
AB  - Independent component analysis (ICA) is a valuable technique for the multivariate
      data-driven analysis of functional magnetic resonance imaging (fMRI) data sets.
      Applications of ICA have been developed mainly for single subject studies,
      although different solutions for group studies have been proposed. These
      approaches combine data sets from multiple subjects into a single aggregate data
      set before ICA estimation and, thus, require some additional assumptions about
      the separability across subjects of group independent components. Here, we
      exploit the application of similarity measures and a related visual tool to study
      the natural self-organizing clustering of many independent components from
      multiple individual data sets in the subject space. Our proposed framework
      flexibly enables multiple criteria for the generation of group independent
      components and their random-effects evaluation. We present real visual activation
      fMRI data from two experiments, with different spatiotemporal structures, and
      demonstrate the validity of this framework for a blind extraction and selection
      of meaningful activity and functional connectivity group patterns. Our approach
      is either alternative or complementary to the group ICA of aggregated data sets
      in that it exploits commonalities across multiple subject-specific patterns,
      while addressing as much as possible of the intersubject variability of the
      measured responses. This property is particularly of interest for a blind group
      and subgroup pattern extraction and selection.

PMID- 15734356
TI  - Accounting for nonlinear BOLD effects in fMRI: parameter estimates and a model
      for prediction in rapid event-related studies.
AB  - Nonlinear effects in fMRI BOLD data may substantially influence estimates of task
      related activations, particularly in rapid event-related designs. If the BOLD
      response to each stimulus is assumed to be independent of the stimulation
      history, nonlinear interactions create a prediction error that may reduce
      sensitivity. When stimulus density differs among conditions, nonlinear effects
      can cause artifactual differences in activation. This situation can occur in
      rapid event-related designs or when comparing blocks of unequal lengths. We
      present data showing substantial nonlinear history effects for stimuli 1 s apart
      and use estimates of nonlinearities in response magnitude, onset time, and time
      to peak to form a low-dimensional parameterization of these nonlinear effects.
      Our estimates of nonlinearity appear relatively consistent throughout the brain,
      and these estimates can be used to form adjusted linear predictors for future
      rapid event-related fMRI studies. Adjusting the linear model for these known
      nonlinear effects results in a substantially better model fit. The biggest
      advantages to using predictors adjusted for known nonlinear effects are (1)
      higher sensitivity at the individual subject level of analysis, (2) better
      control of confounds related to nonlinear effects, and (3) more accurate
      estimates of design efficiency in experimental fMRI design.

PMID- 15734358
TI  - Mapping directed influence over the brain using Granger causality and fMRI.
AB  - We propose Granger causality mapping (GCM) as an approach to explore directed
      influences between neuronal populations (effective connectivity) in fMRI data.
      The method does not rely on a priori specification of a model that contains pre
      selected regions and connections between them. This distinguishes it from other
      fMRI effective connectivity approaches that aim at testing or contrasting
      specific hypotheses about neuronal interactions. Instead, GCM relies on the
      concept of Granger causality to define the existence and direction of influence
      from information in the data. Temporal precedence information is exploited to
      compute Granger causality maps that identify voxels that are sources or targets
      of directed influence for any selected region-of-interest. We investigated the
      method by simulations and by application to fMRI data of a complex visuomotor
      task. The presented exploratory approach of mapping influences between a region
      of interest and the rest of the brain can form a useful complement to existing
      models of effective connectivity.

PMID- 15734357
TI  - Distributions of transmitter receptors in the macaque cingulate cortex.
AB  - The primate cingulate cortex is structurally and functionally complex. Although
      no studies have investigated the regional densities of multiple neurotransmitter
      receptor systems, such information would be useful for assessing its functions
      and disease vulnerabilities. We quantified nine different receptors in five
      transmitter systems by in vitro autoradiographic mapping of the cingulate cortex
      of macaque monkeys with the aim to link cytoarchitectonic regions and functional
      specialization. Receptor mapping substantiated the subdivision of the cingulate
      cortex into anterior versus posterior regions. In anterior cingulate cortex (ACC)
      AMPA glutamatergic receptors and GABA(A) inhibitory receptors were present in
      significantly higher concentrations than the modulatory alpha-adrenergic and
      muscarinic receptors. These differences were absent in the posterior cingulate
      cortex (PCC). By contrast, NMDA receptor densities were significantly higher than
      AMPA receptor densities in PCC, but not in ACC. The midcingulate area 24' shared
      more features with ACC than PCC. This area was characterized by the highest
      ratios of NMDA receptors to alpha-adrenergic, muscarinic and 5-HT2 receptors
      among all cingulate regions. Compared to rostrocaudal divisions, the differences
      between dorsoventral subdivisions a-c were small in all regions of cingulate
      cortex, and only muscarinic and alpha-adrenergic receptor densities followed the
      degree of cytoarchitectonic differentiation. We conclude that multiple receptor
      mapping reveals a highly differentiated classification of cingulate cortex with a
      characteristic predominance of fast ionotropic excitatory and inhibitory
      receptors in ACC, but a strong and varied complement of NMDA and metabotropic
      receptors in PCC.

PMID- 15734359
TI  - Force level independent representations of predictive grip force-load force
      coupling: a PET activation study.
AB  - The existence of forward internal models is a fundamental principle in theories
      of predictive motor control. There are indications that internal models are
      represented in the cerebellum. So far, no conclusive data exist on automated
      procedures involving predictive motor behavior. In particular, it is unknown
      whether single or multiple task-specific internal models handle the broad range
      of behavioral situations in which they occur. Using H2(15)O PET in eight
      subjects, we examined predictive motor control in an automated grip force-load
      force coupling task at three differing load force levels. In the experimental
      condition, subjects pulled a grasped object against an isometric resistance while
      simultaneously producing anticipatory grip forces. There were three control
      conditions (pull force isolated; grip force isolated; motor rest). A 2 x 2
      factorial design was chosen to reveal the interaction effect of grip force-pull
      force coupling. The factors were pull force (with/without) and grip force
      (with/without). Grip and load forces were well matched between experimental and
      control conditions. Conjunction inference and interaction analyses identified
      force coupling related activity in the ipsilateral posterior cerebellum that was
      independent of force levels. Interaction effects were also identified in the
      anterior cingulate and frontal association regions, the right caudate nucleus,
      and the left lingual gyrus. These data demonstrate the existence of modular
      representations for predictive force coupling, with the ipsilateral cerebellum
      playing a major role. Moreover, the data implicate that the representations for
      predictive force control are applicable to a range of different environmental
      affordances.

PMID- 15734360
TI  - Verbal episodic memory impairment in Alzheimer's disease: a combined structural
      and functional MRI study.
AB  - Anatomical and functional MRI images were acquired in a group of healthy elderly
      subjects (n = 11) and a group of patients diagnosed with probable Alzheimer's
      disease, from mild to moderate severity (n = 8). During functional sessions,
      verbal episodic Encoding and Recognition tasks were presented to subjects. Both
      groups were compared in terms of gray matter volume and cerebral activation.
      Furthermore, in the AD group, correlations between hippocampal gray matter volume
      and whole-brain activations were examined. When compared to healthy controls, AD
      patients presented significant gray matter atrophy as well as reduced activations
      during Encoding and Recognition in the medial temporal lobes and inferior
      parietal/superior temporal associative areas. In the same regions, the fMRI
      activity elicited by the Recognition task was positively correlated with
      hippocampal gray matter volume. Moreover, an increase of left prefrontal activity
      during Encoding and Recognition was observed in AD patients relative to controls
      and was correlated with memory performance. This additional activity elicited by
      episodic memory processes was not found to correlate with the degree of medial
      temporal atrophy in our group of patients. Our study shows that function in brain
      regions critical to episodic memory is altered in AD. During episodic
      Recognition, these functional changes may closely correlate with the progressive
      structural changes observed in the hippocampal region.

PMID- 15734361
TI  - Intentional false responding shares neural substrates with response conflict and
      cognitive control.
AB  - The ability to deceive others is a high-level social and cognitive function. It
      has been suggested that response conflict and cognitive control increase during
      deceptive acts but this hypothesis has not been evaluated directly. Using fMRI,
      we tested this prediction for the execution of an intentional false response.
      Subjects were instructed to respond truthfully or falsely to a series of yes/no
      questions that were also varied in autobiographical and nonautobiographical
      content to further examine the influence of personal relevance when lying. We
      observed an interference effect (longer reaction times for false versus true
      responses) that was accompanied by increased activation within the anterior
      cingulate, caudate and thalamic nuclei, and dorsolateral prefrontal cortex
      (DLPFC), a circuit that has been implicated in response conflict and cognitive
      control. Behavioral and neural effects were more robust when falsifying
      autobiographical responses relative to nonautobiographical responses.
      Furthermore, a correlation between reaction time and left caudate activity
      supported the presence of increased response inhibition when falsifying
      responses. When presented with self-relevant (autobiographical) stimuli
      regardless of response condition, the mesial prefrontal and posterior cingulate
      cortices were recruited. Neural activity within these two regions and the
      anterior cingulate cortex (ACC) also showed correlations with self-report
      personality measures from the Psychopathic Personality Inventory (PPI). Overall,
      we conclude that the process of interference is inherent to the act of falsifying
      information and that the amount of conflict induced and cognitive control needed
      to successfully execute false responses is greater when dealing with personal
      information.

PMID- 15734362
TI  - Atlas-guided non-uniform attenuation correction in cerebral 3D PET imaging.
AB  - Photon attenuation in tissues is the primary physical degrading factor limiting
      both visual qualitative interpretation and quantitative analysis capabilities of
      reconstructed Positron Emission Tomography (PET) images. This study investigates
      the implementation and applicability of transmission atlas-guided attenuation
      correction in cerebral 3D PET imaging, thus eliminating the need for acquisition
      of a measured transmission scan. Patient-specific attenuation map is derived by
      anatomic standardization through nonlinear warping of a stereotactic transmission
      template obtained by averaging 11 scans of normal subjects. This template is
      coregistered to a specially designed tracer-specific 18F-[FDG] template
      constructed by scanning 17 normal subjects in resting condition during tracer
      uptake in a dark room. This emission template is first coregistered and spatially
      normalized to preliminary PET images of subjects corrected for scatter and
      attenuation using an approximate calculated method. The resulting transformation
      matrices are recorded and re-applied to the transmission template. The derived
      attenuation map is then forward projected to generate attenuation correction
      factors to be used for correcting the subjects' PET data. Twelve cerebral
      clinical studies are used for evaluation of the developed attenuation correction
      technique as compared to the standard pre-injection measured transmission-based
      method used in clinical routine. Statistical Parametric Mapping (SPM2) analysis
      is used to assess significant differences between images obtained using both
      techniques. The subjective qualitative assessment shows no significant visual
      differences between atlas-guided and transmission-based attenuation correction
      methods. However, the quantitative voxel-based analysis comparing atlas-guided to
      transmission-based attenuation corrections suggest that regional brain metabolic
      activity increases significantly bilaterally in the superior frontal and
      precentral gyri, in addition to the left middle temporal gyrus and the left
      frontal lobe. Conversely, activity decreases in the corpus callosum in the left
      parasagittal region. A new non-uniform attenuation correction method is thus
      proposed, which is suitable for both research and clinical routine applications
      in 3D brain PET imaging on a transmissionless PET scanner or when a patient
      specific transmission scan is not available.

PMID- 15734363
TI  - Voxel-based analysis of multiple-system atrophy of cerebellar type: complementary
      results by combining voxel-based morphometry and voxel-based relaxometry.
AB  - Voxel-based relaxometry (VBR) is a novel morphometric method that analyses the
      relaxation rate R2 derived from multi-echo T2-weighted images on a voxel-by-voxel
      basis. We used VBR to study the brain morphology of 14 patients suffering from
      multiple-system atrophy of cerebellar type (MSA-C) and compared the results with
      those obtained by voxel-based morphometry (VBM) of T1-weighted images. VBR
      analysis revealed reduction of relaxation rate R2 in the cerebellum and brainstem
      reflecting infratentorial brain atrophy. The affected regions largely
      corresponded to those regions in which VBM showed reductions of grey and white
      matter. In addition, R2 was increased in the putamen, a region in which VBM did
      not show abnormalities. Our data show that the combination of VBR and VBM
      provided convergent and complimentary information about the brain morphology of
      MSA-C.

PMID- 15734364
TI  - Tensorial extensions of independent component analysis for multisubject FMRI
      analysis.
AB  - We discuss model-free analysis of multisubject or multisession FMRI data by
      extending the single-session probabilistic independent component analysis model
      (PICA; Beckmann and Smith, 2004. IEEE Trans. on Medical Imaging, 23 (2) 137-152)
      to higher dimensions. This results in a three-way decomposition that represents
      the different signals and artefacts present in the data in terms of their
      temporal, spatial, and subject-dependent variations. The technique is derived
      from and compared with parallel factor analysis (PARAFAC; Harshman and Lundy,
      1984. In Research methods for multimode data analysis, chapter 5, pages 122-215.
      Praeger, New York). Using simulated data as well as data from multisession and
      multisubject FMRI studies we demonstrate that the tensor PICA approach is able to
      efficiently and accurately extract signals of interest in the spatial, temporal,
      and subject/session domain. The final decompositions improve upon PARAFAC results
      in terms of greater accuracy, reduced interference between the different
      estimated sources (reduced cross-talk), robustness (against deviations of the
      data from modeling assumptions and against overfitting), and computational speed.
      On real FMRI 'activation' data, the tensor PICA approach is able to extract
      plausible activation maps, time courses, and session/subject modes as well as
      provide a rich description of additional processes of interest such as image
      artefacts or secondary activation patterns. The resulting data decomposition
      gives simple and useful representations of multisubject/multisession FMRI data
      that can aid the interpretation and optimization of group FMRI studies beyond
      what can be achieved using model-based analysis techniques.

PMID- 15734365
TI  - Viewing facial expressions of pain engages cortical areas involved in the direct
      experience of pain.
AB  - Recent neuroimaging and neuropsychological work has begun to shed light on how
      the brain responds to the viewing of facial expressions of emotion. However, one
      important category of facial expression that has not been studied on this level
      is the facial expression of pain. We investigated the neural response to pain
      expressions by performing functional magnetic resonance imaging (fMRI) as
      subjects viewed short video sequences showing faces expressing either moderate
      pain or, for comparison, no pain. In alternate blocks, the same subjects received
      both painful and non-painful thermal stimulation. Facial expressions of pain were
      found to engage cortical areas also engaged by the first-hand experience of pain,
      including anterior cingulate cortex and insula. The reported findings corroborate
      other work in which the neural response to witnessed pain has been examined from
      other perspectives. In addition, they lend support to the idea that common neural
      substrates are involved in representing one's own and others' affective states.

PMID- 15734367
TI  - A full-size MRI-compatible keyboard response system.
AB  - Two commercially available plastic keyboards were contrasted in the degree to
      which they interfered with echo planar imaging. One keyboard (GrandTec USA's
      "Virtually Indestructible Keyboard") caused significantly less temporally variant
      and invariant signal loss and was integrated into a MRI interface system for
      recording participants' manual motor responses. The response recording system is
      safe, accurately records reaction time behavioral data, and does not interfere
      with functional data collection. Implementing this MRI-compatible keyboard allows
      the collection of motor responses from complex manual behaviors (i.e., typing)
      and thus represents a valuable tool for functional MRI (fMRI) studies.

PMID- 15734366
TI  - The neuroanatomy of general intelligence: sex matters.
AB  - We examined the relationship between structural brain variation and general
      intelligence using voxel-based morphometric analysis of MRI data in men and women
      with equivalent IQ scores. Compared to men, women show more white matter and
      fewer gray matter areas related to intelligence. In men IQ/gray matter
      correlations are strongest in frontal and parietal lobes (BA 8, 9, 39, 40),
      whereas the strongest correlations in women are in the frontal lobe (BA10) along
      with Broca's area. Men and women apparently achieve similar IQ results with
      different brain regions, suggesting that there is no singular underlying
      neuroanatomical structure to general intelligence and that different types of
      brain designs may manifest equivalent intellectual performance.

PMID- 15734368
TI  - Polymerase chain reaction amplification as a diagnostic tool in culture-negative
      multiple-valve endocarditis.
AB  - We report a case of culture-negative infectious endocarditis in a 17-year-old boy
      in which the etiologic diagnosis could only be provided by polymerase chain
      reaction amplification and sequencing of the bacterial 16S rRNA gene from valve
      tissue.

PMID- 15734369
TI  - Neoaortic aneurysm after stage I Norwood reconstruction.
AB  - Treatment of hypoplastic left heart syndrome through staged repairs has resulted
      in patients surviving into adulthood. Use of either aortic or pulmonary
      homografts in performing the neoaortic reconstruction has become the standard of
      practice with relatively few problems. We report the case of an asymptomatic
      adolescent boy who had an enlarging neoaortic aneurysm and mild neoaortic
      regurgitation develop after undergoing a stage I Norwood procedure using a
      pulmonary homograft. Given the risk for rupture and a concern for further
      functional deterioration of the neoaortic valve, the patient underwent repair.
      Histologic examination showed a striking accumulation of myxoid material as well
      as abnormal vasculature in both the native and engrafted portions of the
      neoaorta.

PMID- 15734370
TI  - Lung abscess due to retained gallstones with an adenocarcinoma.
AB  - We describe a patient who had a right lower lobe mass containing calcifications
      consistent with gallstones develop 3(1)/(2) years after laparoscopic
      cholecystectomy. Thoracotomy revealed a chronic abscess containing pigmented
      gallstones and an adjacent area of bronchoalveolar adenocarcinoma involving both
      N1 and N2 lymph nodes.

PMID- 15734371
TI  - Late perforation of the aortic root by an atrial septal defect occlusion device.

PMID- 15734372
TI  - CryoLife-O'Brien stentless valve: 10-year results of 402 implants.
AB  - BACKGROUND: This truly stentless porcine valve is composite, without Dacron, and
      implanted supra-annularly. Ten-year analysis with magnetic resonance imaging is
      presented. METHODS: From 1992 to 2002, 402 patients (mean 73.5 years) had aortic
      valve replacement. Associated procedures were required in 252 patients (63%).
      Serial echoes provided 1340 studies. Clinical follow-up was 100%. Magnetic
      resonance imaging focused on aortic annulus extensibility. RESULTS: The 30-day
      mortality was 0.99% (4 deaths). Morbidity comprised thromboembolism (40 patients
      including 18 patients with permanent strokes); endocarditis (9 patients); and
      reoperation (9 patients [periprosthetic leak, 2; endocarditis, 5; technical
      needle damage, 1; and structural degeneration, 1]). Of 402 valves more than 10
      years, five valves were explanted, one only for structural failure. Except for
      endocarditis (2 patients), no late deaths (69 patients, 1.5 months to 5.7 years)
      were valve related. Echocardiography demonstrated low gradients with good orifice
      areas, excellent ventricular regression (p = 0.0001 preoperative and
      postoperative comparisons) and late incompetence (mild in 45 patients and
      moderate in 9 patients). No living patient has severe incompetence. Magnetic
      resonance imaging demonstrated the annulus 'expanding and relaxing' throughout
      the cardiac cycle, the mean increase in cross-sectional area being 37%,
      resembling normal aortic root dynamics. CONCLUSIONS: Elderly patients received
      this hemodynamically acceptable valve with its simple, supra-annular implantation
      and satisfactory mid-term morbid-free lifestyle to 10 years maximum follow-up.
      With only one structural failure, restoration of valve annular extensibility may
      have a favorable influence on long-term durability.

PMID- 15734373
TI  - Cryopreserved aortic viable homograft for active aortic endocarditis.
AB  - BACKGROUND: To evaluate the short and long-term results of cryopreserved aortic
      viable homograft (CAVH) in the treatment of active aortic endocarditis. METHODS:
      From January 1992 to December 2002, 104 patients (23 females, 81 males) with a
      mean age 51 +/- 13 years (from 14 to 77) underwent CAVH replacement for active
      aortic valve endocarditis. Seventy-six patients (73%) had endocarditis of the
      native aortic valve, 28 (27%) had endocarditis of prosthetic aortic valve; among
      them, eight had a recurrent infection. Eighty-three patients (80%) had isolated
      aortic endocarditis. Plurivalvular endocarditis was observed in 21 (20%)
      patients, (aortic and mitral in 16 patients, aortic and tricuspid in 5).
      Intraoperative transesophageal echocardiography was systematically used.
      Anatomical lesions included perforations in 89 (86%) patients, vegetations in 79
      (77%) patients and periannular extensions in 60 (58%) patients. Precise
      bacteriologic diagnosis was available in 82 (80%) patients. RESULTS:
      Cryopreserved aortic viable homografts were inserted using the aortic root
      replacement technique in 93 (89%) patients and the subcoronary technique in 11
      (11%) patients. Associated procedures were performed in 38 (37%) patients: mitral
      (n = 23) and tricuspid (n = 3) valve repair, partial homograft mitral valve
      replacement (n = 3), partial homograft tricuspid valve replacement (n = 3),
      coronary bypass graft (n = 3), and ascending aorta replacement (n = 3). Hospital
      mortality was 5 (5%) patients. Causes of death included: myocardial infarction (n
      = 2), myocardial failure (n = 2), and multiorgan failure (n = 1). During follow
      up (61 +/- 36 months, from 6 months to 136 months), 9 secondary deaths occurred
      (2 were cardiac related), 14 aortic valvular redo surgeries were performed (2 for
      nonstructural failure, 6 for structural failure, and 6 for endocarditis).
      Actuarial survival at ten years was 83%, with 93% of the patients free from
      cardiac death. At ten years, actuarial rate for freedom from reoperation was 76%
      and freedom from recurrent endocarditis was 93%. No thromboembolic complications
      were observed. CONCLUSIONS: The CAVH has proven its effectiveness in treating the
      destructive lesions of active aortic endocarditis. It has provided satisfactory
      immediate and long-term results. Allowing the possibility to avoid a prosthetic
      material, CAVH could represent an option for surgically treating active aortic
      endocarditis more rapidly.

PMID- 15734374
TI  - Clinical experience with stentless mitral valve replacement.
AB  - BACKGROUND: Our aim is to describe the clinical experience with stentless mitral
      valve (SMV) replacement with special focus on the functionality of the SMV.
      METHODS: Fifty-two patients (68 +/- 8.5 years old; 36 female) have been
      prospectively evaluated since August 1997. The chordally supported SMV (Quattro)
      was implanted for mitral stenosis (n = 26), severe incompetence (n = 17), or
      mixed lesion (n = 9). Preoperative New York Heart Association class was 3.1 +/-
      0.6. Twenty patients received additional intraoperative ablation therapy. Mean
      follow-up is 37.3 +/- 18.7 months (range, 1 to 65). RESULTS: Surgery was
      performed using conventional sternotomy (33) or anterolateral minithoracotomy
      (19). Atrial rhythm was reestablished in 17 of 20 patients. Six patients operated
      on early in this series required reoperation, 2 for paravalvular leakage, 2 for
      functional stenosis, 1 with pannus formation due to underlying rheumatoid
      disease, and 1 for papillary flap rupture after 5.1 years. Mortality was 1
      perioperative (1.9%, nonvalve related) and 1 after reoperation due to multiorgan
      failure. During late follow-up (30 +/- 7 months postoperatively) 5 patients died
      of noncardiac causes. Regular echocardiographic control revealed good SMV
      function (maximum transmitral blood flow velocity 1.7 +/- 0.2 m/s; mean
      transmitral pressure gradient 3.9 +/- 1.2 mm Hg) and well-preserved ejection
      fraction postoperatively as well as at most recent follow-up. CONCLUSIONS: The
      clinical experience after 5.5 years of SMV implantation is promising.
      Preservation of annuloventricular continuity is advantageous. However, long-term
      durability remains to be proved.

PMID- 15734375
TI  - The St. Jude Medical cardiac valve prosthesis: a 25-year experience with single
      valve replacement.
AB  - BACKGROUND: From October 1977 to October 2002, 4,480 patients (age range, 17 to
      94 years; average, 64 +/- 13 years) underwent single valve replacement with the
      St. Jude Medical heart valve. Of 2,982 aortic (AVR) and 1,498 mitral valve
      replacements (MVR), concomitant coronary artery bypass grafting was performed on
      42% and 33%, respectively. METHODS: Cardiac Surgical Associates has maintained an
      independent database of patients having valve replacement with the St. Jude
      Medical prosthesis since the world's first implant. Patients were contacted by
      questionnaire or phone from November 2002 through June 2003. Hospital course and
      valve-related events were verified by patient chart review or physician contact.
      RESULTS: Follow-up was 95% complete. Operative mortality was 4% with AVR and 9%
      with MVR. Total follow-up was 32,190 patient-years (range, 1 month to 24.8 years;
      average, 7 +/- 5 years). During the study period, patient freedom from late
      mortality was 61% (AVR, 61%; MVR, 63%), and from valve-related mortality 92%
      (AVR, 93%; MVR, 91%). Freedom from thromboembolic events was 85% (86% AVR, 81%
      MVR), from bleeding events, 81% (81% AVR, 81% MVR), from reoperation, 98% (99%
      AVR, 97% MVR), from endocarditis, 98% (99% AVR, 98% MVR), and from valve
      thrombosis, 99% (99% AVR, 98% MVR). There was one MVR structural failure (0.06%).
      CONCLUSIONS: The St. Jude Medical valve has proven to be an effective and durable
      valve prosthesis with a low event rate during the long term.

PMID- 15734377
TI  - A 10-year experience with the Carbomedics cardiac prosthesis.
AB  - BACKGROUND: There are few reports on the long-term results of Carbomedics
      prosthetic heart valves. METHODS: Five hundred five patients who underwent valve
      replacement with this prosthesis in the aortic or mitral position were chosen for
      this study. Patients' mean age was 57 years. There were 173 aortic (AVR), 253
      mitral (MVR), and 79 double (DVR) valve implants. The mean follow-up was 5.1
      years, and cumulative follow-up was 2,590 patient-years with an overall follow-up
      rate of 99.2%. RESULTS: The early mortality rate for the total population was
      2.8% (AVR 1.2%, MVR 3.6%, DVR 3.8%). Actuarial freedom from thromboembolism at 10
      years was 81.8% +/- 5.1%, 85.7% +/- 3.2%, and 88.8% +/- 6.8% for AVR, MVR, and
      DVR, respectively. At 10 years, 92.7% of AVR, 85.4% of MVR, and 94.7% of DVR
      patients were free of valve-related death. Overall survival rate at 10 years was
      77.6% +/- 4.6%, 71.8% +/- 4.2%, and 81.3% +/- 5.8% for AVR, MVR, and DVR,
      respectively. The linearized rate of thromboembolism was 1.45%/patient-year,
      1.78%/patient-year, 0.67%/patient-year; of major bleeding events, 0.52%/patient
      year, 0.85%/patient-year, 0.45%/patient-year; of valve thrombosis, 0%/patient
      year, 0.25%/patient-year, 0%/patient-year; of prosthetic valve endocarditis,
      0.1%/patient-year, 0.25%/patient-year, 0.22%/patient-year; and of all
      reoperations, 0.31%/patient-year, 0.93%/patient-year, 1.1%/patient-year for AVR,
      MVR, and DVR, respectively. CONCLUSIONS: The Carbomedics prosthetic heart valves
      showed comparable or even better results than those of other mechanical valves
      with respect to morbidity and mortality. These results may justify the use of
      Carbomedics valves as one of the mechanical heart valves.

PMID- 15734378
TI  - Outcome of medical and surgical treatment in patients with acute type B aortic
      dissection.
AB  - BACKGROUND: Optimal treatment of acute type B aortic dissection remain unclear.
      The aim of this study was to assess the clinical outcome of acute type B aortic
      dissection. METHODS: In the last 8 years, 107 patients were admitted for acute
      type B aortic dissection. We medically treated patients at the time of onset with
      antihypertensives. Surgery was considered if there is intractable pain,
      uncontrolled hypertension, severe aortic branch malperfusion, or aneurysm
      expansion. RESULTS: Twenty-nine patients had pleural effusion (27%), 9 patients
      had leg ischemia (8%), 5 patients had impending rupture, and 2 patients had
      aneurysm enlargement exceeding 60 mm on repeated imaging studies. A total of 16
      patients (15%) underwent surgical intervention: 8 extra-anatomical bypass for leg
      ischemia, 1 in situ infrarenal aortoiliac bypass for distal aortic obstruction,
      and 7 thoracic aortic graft replacement. Of the 8 patients with extra-anatomic
      bypass, 3 patients died: 2 patients died of catastrophic aortic rupture 2 and 9
      days after bypass, and 1 patient died of dissection progression to type A lesion
      9 days after bypass. There was no in-hospital death in 92 medically treated
      patients. Follow-up was 92% complete. The mean follow-up duration was 36.1 months
      (range, 2 to 96 months). The 6-month, 1-year, and 5-year survival rates of all
      patients were 96.2 +/- 1.9%, 95.2% +/- 2.1%, and 95.2% +/- 2.1%. CONCLUSIONS:
      Medical treatment of acute type B aortic dissection produced good outcomes.
      Central aortic procedures such as aortic fenestration and endovascular stenting
      should be the preferred methods to treat patients with acute type B aortic
      dissection and leg ischemia because there was high risk of central aortic
      complications after extra-anatomic bypass.

PMID- 15734380
TI  - Long-term integrity of teflon felt-supported suture lines in aortic surgery.
AB  - BACKGROUND: Although the ultimate success of aortic operations depends upon the
      integrity of graft-to-aorta anastomoses, little is known about different
      techniques used to assure their longevity. We report the incidence of reoperation
      for suture line disruptions arising from anastomoses using reinforcement with
      Teflon felt. METHODS: Since 1987, 1475 patients underwent 2281 anastomoses in the
      thoracic aorta (mean 1.55/anastomoses per patient). All patients were followed
      with at least yearly computed tomographic scans, for a total follow-up of 6483.8
      patient-years. Those requiring reoperation were reviewed retrospectively for
      evidence of suture line disruption. RESULTS: Only 34 patients, with a mean age of
      55.1 years old (range 26-85 years old) underwent reoperation for suture-line
      disruptions following vascular graft-to-aorta anastomosis using Teflon felt. The
      previous operation was a Bentall procedure in 15 (44%); ascending aorta
      replacement in 9 (26%); total arch replacement in 6 (18%); descending aorta
      replacement in 2 (6%); thoracoabdominal repair in 1 (3%); and sinus of Valsalva
      repair in 1 (3%). The incidence of suture line disruption was 0.0052 per patient
      year, and 0.0034 per anastomosis-year. The mean interval between operations was
      55.9 months (range 4-180 months). In 21%, the pseudoaneurysm originated from the
      proximal anastomosis; in 71% from the distal anastomosis; in 3% from both; in 3%
      from the innominate artery; and in 3% from a sinus of Valsalva repair. In only 1
      patient was there evidence of infection. Reoperation involved ascending aorta
      replacement in 11 patients, and total arch replacement in 13 patients. Adverse
      outcome, such as hospital death or permanent stroke, occurred in 8% (3 patients).
      CONCLUSIONS: Use of Teflon felt to support aortic suture lines yields a very low
      incidence of suture line disruptions: 1 per 191 patient-years, or 1 per 296
      anastomosis-years. Teflon felt reinforcement provides a secure, long-lasting
      graft-to-aorta anastomosis with minimal risk of infection.

PMID- 15734381
TI  - Emergency coronary artery bypass grafting can be performed safely without
      cardiopulmonary bypass in selected patients.
AB  - BACKGROUND: Patients requiring emergency surgical revascularization are often not
      considered for off-pump coronary artery bypass grafting (OPCAB). METHODS: From
      1996 to 2003, 614 patients underwent emergency coronary artery bypass grafting
      (Society of Thoracic Surgeons definition) at an academic institution. Forty-four
      (7%) of these procedures were performed without cardiopulmonary bypass, while 570
      were conventional coronary artery bypass procedures with cardiopulmonary bypass
      (CABG/CPB). Data were collected prospectively into a computerized database and
      reviewed retrospectively. RESULTS: Though a greater proportion of CABG/CPB
      patients had critical left main stenosis (15.9% vs 38.3%, p = 0.005), other
      preoperative risk factors were similar between groups. Completeness of
      revascularization (No. distal anastomoses/No. diseased vessel systems) was
      significantly greater in the CABG/CPB group (1.51 +/- 0.03 vs 1.25 +/- 0.07, p =
      0.003). There were no differences among individual complication rates (death,
      cardiac reoperation, postoperative myocardial infarction, permanent cerebral
      vascular accident, deep sternal wound infection, renal failure requiring
      hemodialysis, and respiratory failure requiring reintubation). However, the
      combined incidence of these endpoints was significantly lower in the OPCAB group
      (6.8% vs 21.1%, p = 0.038). OPCAB patients received fewer blood transfusions
      (65.9% vs 84.9%, p = 0.004) and had a significantly shorter intensive care unit
      stay (1.47 vs 3.20 days, p = 0.016). In-hospital mortality (0% vs 6.3%, p =
      0.168) and mean postoperative length of stay (5.48 vs 7.03 days, p = 0.414)
      favored OPCAB, but did not reach statistical significance. CONCLUSIONS: Off-pump
      coronary artery bypass can be performed safely and effectively and should be
      considered in selected patients with acceptable hemodynamics undergoing emergency
      coronary revascularization.

PMID- 15734382
TI  - Impact of off-pump coronary bypass grafting on the prevalence of adverse
      perioperative outcome in women undergoing coronary artery bypass grafting
      surgery.
AB  - BACKGROUND: Female gender has been associated with a high prevalence of
      perioperative morbidity and mortality in coronary artery bypass grafting surgery
      (CABG). We attempted to determine a potential benefit of off-pump CABG as
      compared with on-pump CABG (OPCAB) with regard to perioperative outcome in female
      patients. METHODS: Data were prospectively gathered on 2,182 consecutive female
      patients undergoing CABG either with or without cardiopulmonary bypass from 1996
      to 2001. The associations between OPCAB surgery in addition with 22 further
      preoperative patient-related or treatment-related variables and 26 perioperative
      outcome variables were assessed with multivariable logistic regression analysis.
      RESULTS: One hundred fifty-two (7.0%) female patients underwent OPCAB surgery
      during the study period. Women undergoing OPCAB had higher ejection fractions and
      received fewer coronary artery bypass grafts than CABG patients. Surgery using
      OPCAB was associated with shorter hospital stays, less bleeding, less transfusion
      requirements, and lower mortality than CABG. Furthermore, OPCAB surgery was
      independently associated with a lower prevalence of high perioperative
      transfusion requirement, postoperative respiratory insufficiency, postoperative
      renal insufficiency, and dialysis. Prevalence of postoperative blood loss of at
      least 500 mL was significantly higher after OPCAB surgery. CONCLUSIONS: OPCAB in
      female patients undergoing coronary artery bypass surgery is safe and seems to be
      beneficial with regard to perioperative outcome as compared with conventional on
      pump CABG. For that reason, off-pump surgery may be an effective method of
      lowering morbidity and mortality in these relatively high-risk patients.

PMID- 15734384
TI  - Off-pump, in situ internal thoracic artery grafting: a durable treatment for
      single-vessel coronary artery disease.
AB  - BACKGROUND: The value of off-pump in situ left internal thoracic artery to left
      anterior descending coronary artery bypass grafting in single-vessel coronary
      artery disease was assessed by long-term angiographic and clinical data. METHODS:
      One-hundred three randomly selected patients (87 male, 16 female; mean age, 57.4
      +/- 10.5 years) underwent postoperative angiographic control after an average
      postoperative period of 4.8 +/- 2.9 years (up to 8.2 years; a total of 490
      patient-years). RESULTS: Fifty-five patients (52%) were asymptomatic, whereas 31
      (30%) had anginalike chest pain. Ninety-seven patients (94.2%) were in New York
      Heart Association class I or II. Five-year angina-free survival was 81% +/- 5%.
      Of 103 left internal thoracic arteries assessed, 99 were patent (overall patency,
      96.1%). All four cases having occluded grafts had mild native vessel stenoses
      (<80%) before operation. The patency rate was 99% +/- 1% at 3 years, and 93% +/-
      4% at 5 years. The left ventricular segmental wall motion score of the left
      anterior descending coronary arterial distribution improved from 4.1 +/- 1.1 to
      3.7 +/- 0.9 (p = 0.001). Consequently, 15 patients (15%) underwent secondary
      revascularization (11 interventional and 4 surgical) 4.8 +/- 2.1 years after the
      primary operation. The most frequent indication for interventional
      revascularization was atherosclerotic progression in systems other than left
      anterior descending artery. The cases with graft occlusion were treated
      surgically. Five-year freedom from interventional or surgical repeat
      revascularization was 91% +/- 4%. CONCLUSIONS: In addition to the well-documented
      safety and reliability, off-pump in situ left internal thoracic artery grafting
      is also a durable treatment for isolated left anterior descending artery disease,
      in both clinical and angiographic terms.

PMID- 15734385
TI  - Effect of diabetes on outcome and changes in quality of life after coronary
      artery bypass grafting.
AB  - BACKGROUND: An increasing proportion of patients undergoing coronary artery
      bypass grafting are diabetics who are known to carry a higher mortality and
      morbidity in association with operation, but data on whether health-related
      quality of life improves similarly after coronary artery bypass grafting in
      diabetic and nondiabetic patients are limited. We assessed in detail changes in
      health-related quality of life (RAND-36 Health Survey) during the first year
      after coronary artery bypass grafting. METHODS: Seventy-four of the 508 patients
      (14.6%) operated on in a single institution had a history of diabetes and were
      compared to nondiabetics. The RAND-36 Health Survey was used as an indicator of
      quality of life. Assessments were made preoperatively and repeated 12 months
      later. RESULTS: Thirty-day mortality was 2.7% versus 1.6% (p = 0.511) and one
      year survival was 94.6% versus 97.0% (p = 0.287) in the diabetics and
      nondiabetics, respectively. Diabetics improved significantly (p < 0.005) in
      seven, nondiabetics (p < 0.001) in all eight RAND-36 dimensions. Physical
      component summary and mental component summary scores on the RAND-36 improved
      significantly (p < 0.001) in diabetics as well as in nondiabetics. Both groups
      experienced closely similar freedom from anginal symptoms at one year (86.2% vs
      90.5%, p = 0.280). CONCLUSIONS: Although diabetic patients differ from
      nondiabetics having slightly inferior quality of life before and one year after
      coronary artery bypass grafting, they gain similar improvement of quality of life
      in one year after surgery when compared to nondiabetics.

PMID- 15734386
TI  - Different profiles of patients who require dialysis after cardiac surgery.
AB  - BACKGROUND: This study was aimed at evaluating the determinants of postoperative
      dialysis-requiring acute renal failure and at identifying eventual correlations
      between the different etiologic mechanisms and postoperative prognosis. METHODS:
      We evaluated the preoperative and intraoperative features of the 69 out of 6,542
      consecutive cardiac surgery patients who developed postoperative dialysis
      requiring acute renal failure at our Institution during a 10-year period.
      RESULTS: Age, valvular and aortic surgery, hypertension, extracardiac
      vasculopathy, timing of surgery, cardiopulmonary bypass time, and preoperative
      creatinine level greater than 2.0 mg/dL were identified as predictors by
      multivariate analysis. In a second analysis, patients were divided in two groups
      according to the preoperative creatinine level: group A (preoperative creatinine
      2.0 mg/dL or less; 38 cases) and group B (preoperative creatinine 2.1 mg/dL or
      more; 31 cases). The two groups significantly differed in preoperative and
      intraoperative characteristics and in postoperative outcome: group A patients
      were younger, had a lower incidence of cardiac and vascular risk factors and
      comorbidities, were mainly operated on urgent or emergent basis for valvular or
      aortic pathologies, had longer cardiopulmonary bypass and cross-clamp time, and
      worse in-hospital outcome but higher midterm survival. Group B patients were
      older, had a higher prevalence of comorbidities, required more often in-hospital
      or after-discharge dialysis, had lower in-hospital mortality, but reduced midterm
      survival. CONCLUSIONS: Postoperative dialysis-requiring acute renal failure can
      be the result of two different pathophysiological pathways: complicated
      perioperative course due to urgent-emergent surgery or main intraoperative
      technical complications in patients with preoperative normal renal function and
      uncomplicated perioperative course associated with reduced preoperative kidney
      function. The two patient groups significantly differ in baseline preoperative
      features, as well as in in-hospital and in midterm outcome.

PMID- 15734388
TI  - Effects of the postoperative administration of diltiazem on renal function after
      coronary artery bypass grafting.
AB  - BACKGROUND: Radial artery grafts are used for coronary artery bypass grafting
      (CABG), and postoperative antispasm therapy with diltiazem is performed widely.
      Some investigators have warned that diltiazem administration after cardiac
      surgery is harmful to renal function. We designed a retrospective study to
      investigate the renal and hemodynamic effects of the postoperative administration
      of diltiazem in patients undergoing CABG. METHODS: Subjects were 90 consecutive
      CABG patients. All were treated with diltiazem during surgery (a 0.1 mg/kg bolus
      injection followed by continuous infusion at 2 microg x kg(-1) x min(-1)). In the
      50 patients (diltiazem group) with a radial artery graft, intravenous diltiazem
      administration was continued until the oral intake of diltiazem (90 mg/d) was
      begun to avoid graft spasms. In the remaining 40 patients without a radial artery
      graft, diltiazem was not continued postoperatively (control group). Postoperative
      renal function, assessed by serum creatinine level and creatinine clearance, and
      hemodynamic variables (heart rate, arterial pressure, pulmonary wedge pressure,
      cardiac index, left ventricular stroke work index) was compared between the two
      groups. RESULTS: Renal function: Serum creatinine concentrations on postoperative
      days 1 through 7 were lower, and the endogenous creatinine clearance in the early
      postoperative period was higher in diltiazem group than in control group,
      although the differences were not significant. Hemodynamics: Heart rate was lower
      in diltiazem group than in the control group, but blood pressure, pulmonary wedge
      pressure, cardiac index, left ventricular stroke work index, and urinary output
      were similar between the groups. CONCLUSIONS: Our results confirmed that
      intravenous diltiazem treatment in patients undergoing CABG is not harmful to
      renal function.

PMID- 15734390
TI  - Determinants and prognosis of myocardial damage after coronary artery bypass
      grafting.
AB  - BACKGROUND: Myocardial infarction remains a devastating complication after
      coronary revascularization. Although electrocardiography (ECG) and
      echocardiography suggest transmural infarction, myocardial damage and the quality
      of myocardial protection are not recognized unless troponin I (TnI) is assessed.
      Determinants and prognosis of TnI elevation after coronary artery bypass grafting
      (CABG) were evaluated. METHODS: Data of 776 consecutive patients undergoing CABG
      between January 2002 and January 2004 were prospectively exposed to univariate
      and multivariate analysis. We evaluated the prognosis of patients with all the
      ECG, echocardiographic, and biochemical criteria for acute myocardial infarction
      and that of patients with only TnI elevation. Twelve-month follow-up survival and
      freedom from cardiac events (FCE) were accomplished. RESULTS: Troponin I greater
      than 3.1 mug/L at 12 hours was detected in 6.9% of the population, and correlated
      with lower in-hospital (p < 0.001) and follow-up survival (p = 0.00001), and
      lower FCE (p = 0.0009). Twenty-one (38.8%) of these fulfilled ECG
      echocardiographic criteria (p = 0.05), demonstrating higher TnI values at 12 (p =
      0.001), 24 (p = 0.01), 48 (p = 0.01), and 72 (p = 0.04) hours, prolonged
      ventilation time (p = 0.001), higher in hospital mortality (p = 0.003), lower
      follow-up survival (p = 0.023), and lower FCE (p = 0.0084). A EuroSCORE greater
      than 6, ongoing unstable angina, aortic cross-clamp time greater than 90 minutes,
      cardiopulmonary bypass time greater than 180 minutes, incomplete
      revascularization, and intraoperative intraaortic balloon pump were independent
      predictors of myocardial damage (MD) at multivariate analysis. Combined antegrade
      and retrograde cardioplegia and postoperative enoximone infusion were associated
      with a lower TnI elevation. CONCLUSIONS: Troponin I greater than 3.1 mug/L at 12
      hours defines perioperative MD. Associated ECG-echocardiographic criteria
      indicate acute myocardial infarction and anticipate a worse outcome.
      Identification of predictors for MD is important to develop preventative
      strategies, as antegrade plus retrograde cardioplegia and enoximone infusion.

PMID- 15734391
TI  - Optimal method of coronary endarterectomy for diffusely diseased coronary
      arteries.
AB  - BACKGROUND: Although several techniques for coronary artery bypass grafting have
      been introduced that incorporate coronary endarterectomy (CE), there is little
      information about late patency among the various CE methods. To clarify the
      quality of CE, we assessed clinical and angiographic results of our experience
      with this procedure on 127 patients who had diffusely diseased coronary arteries.
      METHODS: Between January 1994 and December 2002, 127 patients underwent coronary
      artery bypass grafting with CE. Sixty-eight patients undergoing CE with long
      arteriotomies and on-lay patch bypass grafting (group O) were compared with 59
      patients undergoing CE with the conventional pull-out method (group P). RESULTS:
      Thirty-day mortality was 2.9% in group O and 6.8% in group P. The early
      angiographic results of 115 patients revealed a patency rate of 92.1% (grade A:
      79.4%) in group O and 88.6% (grade A: 68.6%) in group P. Actuarial survival at 5
      years was 90.7% in group O and 74.0% in group P (p = 0.1). Angiograms performed
      on 78 patients after a mean period of 21 +/- 16 months showed a patency rate of
      89.1% (grade A:76.1%) in group O and 81.0% (grade A: 38.1%) in group P (grade A:
      p < 0.001). CONCLUSIONS: The midterm angiographic results of CE with long
      arteriotomies and on-lay patch bypass grafting were better than the results
      obtained with the conventional pull-out method. This procedure was found to be
      safe and effective for complete revascularization in patients with a severely and
      diffusely diseased coronary artery.

PMID- 15734393
TI  - Transit-time flow measurement is essential in coronary artery bypass grafting.
AB  - BACKGROUND: Patent bypass grafts are fundamental to successful coronary artery
      bypass grafting. Intraoperative flow measurement through newly constructed grafts
      is a test of patency. We studied the use of transit-time flow measurement to
      determine its ability to detect technical errors in grafts, to measure the mean
      flow norms for Asian patients, and to compare arterial and vein grafts. METHODS:
      From January 1, 2001, to June 30, 2002, 116 patients underwent isolated primary
      coronary artery bypass grafting. Sixty-seven patients underwent conventional
      coronary artery bypass grafting and 49 patients underwent off-pump coronary
      artery bypass grafting. There were 125 arterial and 197 vein grafts. Transit-time
      flow measurement was carried out on all completed grafts. Graft patency was
      assessed using flow curves, mean flow, and pulsatility index. Average of mean
      flows was calculated to determine mean flow norms. Arterial and vein grafts were
      compared by statistical analysis between the variables mean flow and pulsatility
      index. RESULTS: In 6 patients with seven grafts, intraoperative graft assessment
      detected technical errors, which were corrected. Average mean flow was 37.4 +/-
      23.5 mL/min for left anterior descending coronary artery-to-left internal mammary
      artery grafts, and values ranging from 21.2 to 36.0 mL/min for the rest. There
      were no statistically significant differences in mean flow or pulsatility index
      between arterial and vein grafts. CONCLUSIONS: Transit-time flow measurement
      enables technical problems to be diagnosed accurately, allowing prompt revision
      of grafts. It should be mandatory in coronary artery bypass grafting to improve
      surgical outcomes.

PMID- 15734395
TI  - P-wave signal-averaged electrocardiogram for predicting atrial arrhythmia after
      cardiac surgery.
AB  - BACKGROUND: Atrial arrhythmias (AF) are usually benign, but occur frequently
      after cardiac surgery. P-wave signal-averaged electrocardiogram has been used to
      characterize atrial conduction delay as a marker of risk of AF during sinus
      rhythm. METHODS: Ninety-five patients undergoing either primary isolated coronary
      artery bypass grafting or aortic valve replacement were enrolled. The duration
      and the root mean square voltage for the last 20 ms of filtered (40 to 300 Hz) P
      wave of the spatial magnitude were recorded before surgery. Any episode of
      postoperative atrial fibrillation, atrial flutter, or paroxysmal atrial
      fibrillation lasting longer than 1 hour was considered as AF. RESULTS: Twenty
      eight patients (29%) exhibited AF 3.0 +/- 2.3 days after surgery. The P-wave
      duration recorded with P-wave signal-averaged electrocardiogram was significantly
      prolonged in patients with AF (135 +/- 14 ms versus 127 +/- 9 ms; p = 0.002).
      Patients with AF more often had dilated left atrium (p = 0.003), left ventricular
      hypertrophy (p = 0.03), and advanced age (p = 0.02). Logistic regression analysis
      identified the following three variables as predictive of AF: P-wave duration of
      135 ms or greater (p = 0.02; odds ratio, 3.5), patients 70 years of age and older
      (p = 0.03; odds ratio, 3.2), and left atrial dimension of 35 mm or greater (p =
      0.03; odds ratio, 3.2). If a patient had two or more of these three risk factors,
      the occurrence of AF was predicted with a sensitivity of 75%, specificity of 76%,
      positive predictive accuracy of 57%, and negative predictive accuracy of 88%.
      CONCLUSIONS: The prolonged P-wave duration recorded with P-wave signal-averaged
      electrocardiogram, together with advanced age and left atrial enlargement, is a
      potent and independent predictor of AF after cardiac surgery. Patients with these
      risk factors may benefit from prophylactic antiarrhythmic treatment.

PMID- 15734396
TI  - Association of high intracellular, but not serum, heat shock protein 70 with
      postoperative atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is a common arrhythmia, after cardiac surgery.
      Reperfusion injury and inflammation associated with cardiac surgery are thought
      to be involved in its pathogenesis. We hypothesized that cytoprotective effects
      associated with heat shock protein 70 (HSP70) could counteract these
      proarrhythmic insults. We therefore set out to examine the influence of heat
      shock protein 70 on the incidence of postoperative atrial fibrillation. METHODS:
      We prospectively recruited 80 patients undergoing elective coronary artery bypass
      surgery. Blood samples were collected preoperatively. Right atrial tissue was
      obtained at surgery. Incidence of postoperative atrial fibrillation and its
      duration were noted. Using a nested case-control design, 15 patients who
      developed atrial fibrillation were matched for operative procedure, age, sex, and
      beta-blocker usage, with 15 controls from the remaining patients. Atrial heat
      shock protein 70 was subsequently quantified by immunohistochemistry. Serum heat
      shock protein was measured using enzyme-linked immunosorbent assay and high
      sensitivity C-reactive protein was determined by immunoturbidometric assay.
      RESULTS: Intracellular HSP70 level was significantly higher in patients who did
      not develop atrial fibrillation (35 +/- 13 vs 19 +/- 15; p = 0.006). Atrial HSP70
      level negatively correlated with atrial fibrillation; independent of other risk
      factors (odds ratio = 0.90; 95% confidence interval 0.84 to 0.99, p = 0.02).
      Serum HSP70 levels were similar in both groups (p = 0.81) and did not correlate
      with intracellular levels (p = 0.38). Preoperative C-reactive protein levels were
      similar in both groups (p = 0.93). CONCLUSIONS: Intracellular, but not serum,
      HSP70 level is negatively correlated with postoperative atrial fibrillation. This
      suggests a cardioprotective and an antiarrhythmic role for intracellular HSP70.

PMID- 15734398
TI  - Beat-to-beat effects of intraaortic balloon pump timing on left ventricular
      performance in patients with low ejection fraction.
AB  - BACKGROUND: Intraaortic balloon counterpulsation (IABP) timing errors during
      arrhythmia may result in afterload increases which may negatively influence left
      ventricular (LV) ejection and LV mechanical dyssynchrony. The aim of our study
      was to determine beat-to-beat effects of properly timed IABP, premature IAB
      inflation, and late IAB deflation on LV performance and LV mechanical
      dyssynchrony in heart failure patients undergoing cardiac surgery. METHODS: In 15
      patients, LV pressure-volume relations and LV dyssynchrony were measured by
      conductance volume catheter. Properly timed IABP was evaluated at a 1:1 assist
      ratio within a 10 seconds time-span. Premature IAB inflation and late IAB
      deflation were evaluated at a 1:4 assist ratio. RESULTS: Properly timed 1:1 IABP
      acutely decreased LV end-systolic volume by 6.1% (p < 0.0001) and LV end-systolic
      pressure by 17.5% (p < 0.0001) due to decreased aortic impedance. Stroke volume
      (SV) increased by 14% (p < 0.0001), which correlated markedly with a decrease of
      LV mechanical dyssynchrony (p < 0.0001). The largest SV increases occurred in
      patients with lowest contractile state. Premature IAB inflation decreased SV by
      20% (p < 0.0001) due to abrupt increase of LV afterload during late ejection.
      Late IAB deflation increased SV and stroke work by 18% (p < 0.0001) and 16% (p <
      0.01) respectively, due to increased afterload during early ejection and
      decreased afterload during late ejection. CONCLUSIONS: Left ventricular
      performance during IABP is causally related to changes in LV afterload, and the
      timing of these changes in relation to contraction or relaxation phases, to LV
      mechanical dyssynchrony and to contractile state.

PMID- 15734399
TI  - Early ventricular restraint after myocardial infarction: extent of the wrap
      determines the outcome of remodeling.
AB  - BACKGROUND: Early infarct expansion initiates adverse remodeling, leads to left
      ventricular dilatation and portends a poor long-term outcome. Early mechanical
      prevention of infarct expansion has been proposed as a method to improve
      remodeling, but the extent of ventricular restraint necessary to optimize the
      salutary effect is not known. We tested the hypothesis that left ventricular
      restraint (wrap) is superior to infarct stiffening (patch). METHODS: Infarction
      of 20% to 25% of the left ventricle was induced by coronary ligation in 69 sheep.
      Infarcts were either anteroapical (n = 33) or posterobasal (n = 36). Animals with
      each infarct received either no treatment (anteroapical, n = 26; posterobasal, n
      = 17), infarct stiffening with a localized Marlex mesh patch (posterobasal, n =
      9) or left ventricular wrapping with Merseline mesh (anteroapical, n = 7;
      posterobasal, n = 10). End-systolic volume, end-diastolic volume, end-systolic
      muscle to cavity area ratio, left ventricular sphericity, ejection fraction, and
      degree of mitral regurgitation as determined by quantitative echocardiography
      were assessed before infarction and at 2, 5, and 8 weeks after infarction to
      evaluate the extent of left ventricular remodeling. RESULTS: Control animals in
      both groups experienced adverse remodeling. Anteroapical infarct animals
      developed large left ventricular aneurysms and the posterobasal infarct animals
      developed severe mitral regurgitation. Early infarct stiffening did not
      significantly improve any aspect of remodeling due to the posterobasal infarct.
      Early left ventricular wrapping significantly improved remodeling after both
      types of infarctions. CONCLUSIONS: Early left ventricular wrapping attenuates
      infarct expansion and has a salutary effect on remodeling. Simple infarct
      stiffening alone is not effective.

PMID- 15734400
TI  - Recellularization of decellularized allograft scaffolds in ovine great vessel
      reconstructions.
AB  - BACKGROUND: Decellularized allograft tissues have been identified as a potential
      extracellular matrix (ECM) scaffold on which to base recellularized tissue
      engineered vascular and valvular substitutes. Decreased antigenicity and the
      capacity to recellularize suggest that such constructs may have favorable
      durability. Detergent/enzyme decellularization methods remove cells and cellular
      debris while leaving intact structural protein "scaffolds." Allograft pulmonary
      artery tissues decellularized with an anionic detergent/enzyme methodology were
      tested in a long-term implantation model that used arterial wall repairs in the
      great vessels of juvenile sheep. METHODS: Twelve test sheep were implanted (n =
      4) for each of three different scaffold protocols that compared traditional
      dimethylsulfoxide cryopreservation, cryopreservation followed by
      decellularization, and decellularization of fresh tissue. Four additional sheep
      served as controls (n = 2 sham, n = 2 fresh tissue). Patches were fashioned and
      implanted into pulmonary artery and aortic defects. Panel reactive antibodies
      (PRA) were measured over time (10 to 20 weeks). Explant histopathology determined
      recellularization morphology as well as calcium, collagen, and elastin
      distribution within explanted tissue. RESULTS: Unlike traditionally cryopreserved
      tissues, the decellularized tissues contained no residual cells or cellular
      debris before implantation, which correlated with measurable reductions in PRA.
      Decellularized explants demonstrated time-dependent migration of recipient cells
      through matrix, typically staining positive for alpha-smooth muscle actin with no
      calcification. CONCLUSIONS: The properties demonstrated seem consistent with
      characteristics necessary for implantable tissue-engineered scaffolds. The
      decellularization method described appears to create a biologically suitable ECM
      scaffold for in vivo migration of phenotypically appropriate cells while avoiding
      antigenicity and calcification.

PMID- 15734402
TI  - Prevention of calcification of bioprosthetic heart valve cusp and aortic wall
      with ethanol and aluminum chloride.
AB  - BACKGROUND: Calcification is frequently associated with device failure of
      bioprostheses fabricated from either glutaraldehyde pretreated porcine aortic
      valves or bovine pericardium. It was hypothesized that differential pretreatment
      with ethanol-aluminum chloride will prove safe and efficacious for inhibiting the
      calcification of both the porcine aortic valve bioprosthetic cusp and the aortic
      wall. METHODS: Glutaraldehyde-fixed porcine aortic valves were subjected to
      differential aluminum chloride (AlCl3) and ethanol pretreatment; aortic wall
      segments were treated exclusively with AlCl3 (0.1 moles/L) for 45 minutes, 6
      hours, or 8 hours (groups 3A, B, and C, respectively), followed by valve cusp
      incubations in ethanol (80%, pH 7.4). Nontreated control bioprosthetic valves
      were either stent-mounted porcine aortic valve bioprostheses (Carpentier-Edwards,
      group 1) (Edwards, Santa Anna, CA) or St. Jude Toronto SPV valves (St. Jude
      Medical, St. Paul, MN) (group 2). Mitral valve replacements were carried out in
      juvenile sheep for 150 days. RESULTS: Calcium in cusps from group 3A was 2.84 +/-
      0.62 mg calcium/g tissue versus control, 22.79 +/- 8.46 mg calcium/g tissue, p =
      0.04. Valves pretreated with AlCl3 for 45 minutes, 6 hours, and 8 hours had
      significantly lower levels of calcium in the aortic wall compared to controls
      (40.38 +/- 5.66, 26.77 +/- 4.02, and 28.94 +/- 8.25 mg calcium/g tissue for
      groups 3A, 3B, and 3C, respectively, vs 95.47 +/- 17.14 mg calcium/g tissue for
      group 1, p < 0.001, and 133.42 +/- 3.96 mg calcium/g tissue for group 2, p <
      0.001). CONCLUSIONS: Differentially applied ethanol and aluminum chloride
      pretreatment significantly inhibited calcification of both the glutaraldehyde
      fixed porcine aortic valve bioprosthetic cusp and the aortic wall.

PMID- 15734403
TI  - Carbodiimide treatment dramatically potentiates the anticalcific effect of alpha
      amino oleic acid on glutaraldehyde-fixed aortic wall tissue.
AB  - BACKGROUND: Bifunctional amines were previously found to act as bridging
      molecules between the terminal ends of incomplete glutaraldehyde (GA) cross
      links. The additional cross-links thus formed between -NH2 groups of tissue were
      seen to significantly inhibit bioprosthetic calcification. In the current study,
      the potential ability of alpha-amino oleic acid (AOA) to act as a bridging
      molecule between -NH2- and COOH-dependent cross-links was hypothesized to
      similarly augment the anticalcification effect of the AOA molecule. METHODS:
      Porcine aortic wall tissue from Medtronic Freestyle valve bioprostheses
      incorporating the AOA anticalcification process additionally underwent carboxyl
      group cross-linking with Jeffamine (poly[propylene glyco]-bis-[aminopropyl
      ether]) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Tissue was
      subdermally implanted into 5-week-old Long-Evans rats for 60 days. Standard 0.2%
      GA-fixed tissue served as a control. To further assess the impact of storage
      solution on AOA tissue, samples were either stored in GA (0.2%GA) or EDC (25
      mmol/L carbodiimide) before implantation. Tissue calcification was assessed by
      atomic absorption spectroscopy and histochemical staining. RESULTS: Aldehyde end
      capping with AOA achieved only a modest reduction of calcification in GA-treated
      aortic wall tissue (-20.0%; p < 0.05). Replacing GA with EDC as a storage
      solution led to a further 32.4% (p < 0.01) mitigation of calcification in
      Freestyle tissue. Incorporating an intermediate EDC/Jeffamine cross-linking step
      achieved a distinct additional reduction of calcification by 40.4% (p < 0.05).
      Overall, aortic wall calcification was 59.7% (p < 0.0001) lower if commercial
      Freestyle tissue underwent an additional EDC/Jeffamine cross-linking step and
      subsequent storage in EDC. Relative to control GA-fixed tissue, this represented
      a 67.8% (p < 0.0001) reduction. Incorporation of AOA was essential for the
      beneficial effect of the additional EDC/Jeffamine cross-linking step.
      CONCLUSIONS: Potentially utilizing both the amino- and the carboxyl moieties of
      AOA for tissue binding dramatically reduces aortic wall calcification of GA-fixed
      tissue.

PMID- 15734404
TI  - Bradykinin preconditioning preserves coronary microvascular reactivity during
      cardioplegia-reperfusion.
AB  - BACKGROUND: Alterations of microvascular reactivity reduce myocardial perfusion
      after ischemic cardioplegia. We hypothesized that bradykinin preconditioning
      (BKPC) would preserve endothelium-dependent microvascular responses and improve
      myocardial function after cardioplegic ischemia-reperfusion. METHODS: Rabbit
      hearts were perfused with Krebs-Henseleit buffer (KHB). The hearts were arrested
      for 60 minutes with moderately cold (25 degrees C) crystalloid cardioplegia
      (MCCP, n = 8) or with cold (0 degrees to 4 degrees C) crystalloid cardioplegia
      (CCCP) (n = 6). The BKPC hearts received a 10-minute coronary infusion of 10(-8)
      M BK-enriched KHB, followed by a 5-minute recovery period, and then were arrested
      for 60 minutes with MCCP (BKPC + MCCP, n = 8) or with CCCP (BKPC + CCCP, n = 6).
      The hearts were reperfused for 30 minutes with KHB. Six control hearts were
      perfused with KHB for 90 minutes without cardioplegia-ischemia. Left ventricle
      performance was measured, and in vitro relaxation responses of precontracted
      coronary arterioles (internal diameter, 80 to 150 mum) were obtained in a
      pressurized no-flow state. RESULTS: Ischemic arrest with MCCP or CCCP markedly
      reduced endothelium-dependent relaxation to adenosine 5'-diphosphate, substance
      P, and calcium ionophore (A23187). Both MCCP and CCCP significantly enhanced
      contractile responses to U46619 (10(-7) M), a thromboxane A2 analogue, compared
      with control (p < 0.05). In contrast, BKPC significantly improved the recovery of
      endothelium-dependent relaxation to adenosine 5'-diphosphate, substance P, and
      A23187 compared with MCCP or CCCP, respectively. BKPC reduced the contractile
      responses to U46619 compared with MCCP or CCCP. BKPC also improved postischemic
      performance compared with MCCP or CCCP alone (p < 0.05). CONCLUSIONS: BKPC
      preserves endothelium-dependent microvascular responses and prevents the
      hypercontractility to U46619. These effects may provide increased coronary
      perfusion and prevent arteriolar spasm after open heart surgery. They suggest
      that BK preconditions the coronary microvasculature during cardiovascular
      surgery.

PMID- 15734405
TI  - Differential effect of heparin coating and complement inhibition on artificial
      surface-induced eicosanoid production.
AB  - BACKGROUND: Contact between blood and artificial surfaces induces an inflammatory
      response including activation of leukocytes and platelets, as well as complement
      and other plasma cascade systems. In the present study we investigated the roles
      of complement and surface modification in polyvinyl chloride-induced synthesis of
      eicosanoids (arachidonic acid metabolites). METHODS: Human whole blood was
      incubated in rotating loops of polyvinyl chloride or heparin-coated polyvinyl
      chloride tubing for 4 hours. Plasma concentrations of the eicosanoids leukotriene
      B4, prostaglandin E2 and thromboxane B2 were quantified. RESULTS: Polyvinyl
      chloride induced a substantial increase in leukotriene B4, prostaglandin E2, and
      thromboxane B2. Inhibition of complement activation by the complement factor 3
      binding peptide compstatin or blockade of the complement factor 5a receptor with
      a specific antagonist significantly and specifically inhibited the synthesis of
      leukotriene B4, whereas thromboxane B2 and prostaglandin E2 synthesis were
      apparently complement independent. The increase in all three mediators was
      significantly reduced by the heparin coating. Indomethacin abolished the increase
      of the cyclooxygenase products prostaglandin E2 and thromboxane B2, but had no
      effect on the increase of the lipoxygenase product leukotriene B4, consistent
      with the specificity of indomethacin for the cyclooxygenase and confirming the
      specificity of complement inhibition. CONCLUSIONS: Polyvinyl chloride-induced
      increase in all three eicosanoids was attenuated by heparin coating, whereas
      complement inhibition selectively reduced the synthesis of leukotriene B4.

PMID- 15734406
TI  - Initial experience with a bicuspid polytetrafluoroethylene pulmonary valve in 41
      children and adults: a new option for right ventricular outflow tract
      reconstruction.
AB  - BACKGROUND: As the population of children with repaired congenital heart disease
      ages, an increasing number of patients will benefit from pulmonary valve
      insertion. We report our initial experience in 41 consecutive patients treated
      with placement of a surgically created polytetrafluoroethylene bicuspid pulmonary
      valve. METHODS: A bicuspid pulmonary valve with orifice size greater than 24 mm
      is created with polytetrafluoroethylene and sutured into the right ventricular
      outflow tract. To obviate the need for reoperation in growing children, this
      technique is limited to older children and adults. Polytetrafluoroethylene
      bicuspid pulmonary valves were placed in 41 patients (age: range, 5.0 to 64.7
      years, median = 15.7 years; weight: range, 14.2 to 99.0 kilograms, median, 52.0
      kg). All patients had pulmonary insufficiency, pulmonary stenosis, or both, after
      previous intervention for tetralogy of Fallot (27), pulmonary stenosis (11),
      pulmonary atresia with intact ventricular septum (2), or double outlet right
      ventricle (1). RESULTS: All patients left the operating theater with
      transesophageal echocardiography documenting no pulmonic stenosis and zero to
      trace pulmonic insufficiency. Median hospital length of stay was 5 days (range, 3
      to 15 days; mean, 5.8 days). Follow-up including echocardiography ranged from 0.2
      to 3.1 year (median follow-up, 1.5 years) and revealed significant improvement in
      New York Heart Association Classification, pulmonary insufficiency, and right
      ventricular end diastolic dimension. CONCLUSIONS: Polytetrafluoroethylene
      bicuspid pulmonary valve reconstruction of the right ventricular outflow tract is
      a safe, effective, and durable technique for the short term. Appropriate
      oversizing minimizes outflow tract obstruction while maximizing competence. Long
      term follow-up is necessary to determine the true value of this technique.

PMID- 15734407
TI  - Acute hemodynamic benefit of left ventricular apex pacing in children.
AB  - BACKGROUND: Despite the fact that pacing at the right ventricular apex acutely
      and chronically decreases left ventricular contractile function, this pacing site
      is still conventionally used in adults and children. Because animal studies
      showed beneficial effects of left ventricular pacing, we compared the hemodynamic
      performance of left ventricular apex, left ventricular free wall, and right
      ventricular apex pacing in children. METHODS: Studies were performed in 10
      children (median age, 2.5 years; range, 2 months to 17 years) undergoing surgery
      for congenital heart disease with normal systemic left ventricular anatomy and
      intraventricular conduction. High-fidelity left ventricular and arterial pressure
      measurements were performed during epicardial right ventricular apex and left
      ventricular apex and free wall pacing. RESULTS: Left ventricular apex pacing
      increased the maximum rate of rise of left ventricular pressure and pulse
      pressure significantly relative to right ventricular apex pacing (by 7.7% +/-
      7.2% and 7.7% +/- 7.0%, respectively) without changes in end-diastolic left
      ventricular pressure. Left ventricular free wall pacing did not significantly
      improve hemodynamics as compared with right ventricular apex pacing. The QRS
      duration was not different among pacing at the three sites. CONCLUSIONS: In this
      short-term study left ventricular apex pacing is hemodynamically superior to
      right ventricular apex and left ventricular free wall pacing in children.
      Therefore, the left ventricular apex appears a favorable pacing site after
      pediatric cardiac surgery.

PMID- 15734408
TI  - Selective annuloplasty for tricuspid regurgitation in children.
AB  - BACKGROUND: Tricuspid valve regurgitation occurs with other congenital heart
      defects, especially the right-sided obstructive lesions. We applied the selective
      annuloplasty technique for the treatment of tricuspid regurgitation in children.
      METHODS: Between 2001 and 2003, 15 patients whose ages averaged 7.6 +/- 3.1 years
      (range 4 to 17 years old) underwent selective annuloplasty during correction of
      other heart defects. The patients had repair of pulmonary stenosis (5 patients),
      pulmonary stenosis and ventricular septal defect (7 patients), and tetralogy of
      Fallot (3 patients). Eight patients preoperatively had moderate tricuspid
      regurgitation, and 7 patients had severe tricuspid regurgitation. RESULTS: No
      deaths nor heart block occurred after the operation. The length of the tricuspid
      regutgitation flow was significantly decreased from 2.9 +/- 0.7 cm before the
      operation to 0.9 +/- 0.6 cm after the operation (p < 0.01), and the tricuspid
      annular diameter decreased from 3.9 +/- 0.3 cm to 3.3 +/- 0.3 cm (p < 0.01).
      Annular circumference was reduced by 1.9 +/- 0.2 cm. No tricuspid regurgitation
      was detected in 3 patients (20%), mild tricuspid regurgitation was seen in 10
      (67%), moderate tricuspid regurgitation in 2 (13%). The right atrial mean
      pressure was significantly decreased from 7.5 +/- 0.5 mm Hg before the operation
      to 3.1 +/- 0.2 mm Hg after the operation (p < 0.01), right ventricular systolic
      pressure from 55.5 +/- 2.3 mm Hg to 29.8 +/- 1.9 mm Hg (p < 0.01), and right
      ventricular end-diastolic pressure from 8.4 +/- 0.7 mm Hg to 4.9 +/- 0.9 mm Hg (p
      < 0.01). Preoperatively, the degree of tricuspid regurgitation flow correlated
      significantly with the right ventricular systolic pressure (r = 0.89; p < 0.001).
      There was no correlation between tricuspid regurgitation flow and right
      ventricular systolic pressure postoperatively (p = 0.88). No child has
      symptomatic or significant tricuspid stenosis. CONCLUSIONS: Selective
      annuloplasty presents a useful procedure for young patients with moderate or
      severe tricuspid regurgitation and right-sided obstructive lesions resulting from
      functional reconstruction of the tricuspid valve.

PMID- 15734409
TI  - Tracheal regeneration following tracheal replacement with an allogenic aorta.
AB  - BACKGROUND: Tracheal replacement remains an unsolved surgical problem. Attempts
      to use tracheal substitutes have failed to achieve reliable results. In this
      study, tracheal regeneration was obtained after tracheal replacement with an
      allogenic aorta. METHODS: Twenty female sheep underwent a 8-cm tracheal
      replacement with a fresh aortic allograft. In the six last animals, aortic grafts
      came from male sheep. A stent prevented airway collapse. No immunosuppressive
      therapy was used. Aortic segments were retrieved at regular intervals up to 16
      months. A polymerase chain reaction for the SRY gene was performed in specimens
      with aortic grafts from male sheep. RESULTS: All animals but one survived the
      operation without complications. Clearly identified between the suture lines, the
      aortic segments were completely transformed into a tracheal structure. Histology
      showed initially an inflammatory reaction with proliferation of a squamous
      epithelium followed by mucociliary epithelium and newly formed cartilage rings.
      SRY gene was not found in newly formed cartilage rings showing that the
      regeneration originated from recipient cells. CONCLUSIONS: This study presents a
      new type of tissue regeneration and brings hopes to the treatment of extensive
      tracheal lesions.

PMID- 15734411
TI  - Impact of recipient age and procedure type on survival after lung transplantation
      for pulmonary fibrosis.
AB  - BACKGROUND: The decision to perform single-lung (SLT) or bilateral sequential
      lung (BSLT) transplantation in patients with pulmonary fibrosis is controversial.
      Some centers use recipient age (<50 years) as a criterion to select BSLT over
      SLT, but the rationale for this approach is not well established. METHODS: Eight
      hundred twenty-one patients (636 SLT, 185 BSLT), aged 30 to 69 years, who were
      recipients of transplants for pulmonary fibrosis in the United States between
      1994 and 2000 were reported to the United Network for Organ Sharing. Survival was
      compared by procedure type within three age groups (30 to 49 years, 50 to 59
      years, and 60 to 69 years) using the Kaplan-Meier method. Multivariate logistic
      regression analysis was used to calculate risk-adjusted mortality within 1-month
      after transplantation, and proportional hazards regression was used to calculate
      risk-adjusted mortality after 1 month. RESULTS: Early (1-month) and late (3-year)
      survival in recipients aged 30 to 49 years was significantly better with SLT than
      BSLT (early, 90.9% versus 77.1%; late, 63.8% versus 46.2%, respectively; p =
      0.02). Survival was also significantly better with SLT than BSLT at these time
      points in those patients aged 50 to 59 years (early, 89.5% versus 81.7%; late,
      53.6% versus 46.7%, respectively; p = 0.03). When posttransplant survival was
      reanalyzed contingent on survival to 1 month, no significant difference in
      survival by procedure type (SLT versus BSLT) was detected for any age group.
      Multivariate analysis of survival, adjusted for other known risk factors, as well
      as propensity analysis, yielded similar results. CONCLUSIONS: Patients younger
      than 60 years of age who were recipients of transplants for pulmonary fibrosis
      appear to have better survival with SLT than with BSLT. Although the basis for
      this observation is unclear, events occurring in the early period (first month)
      after transplantation may play a role. Further studies will be needed, but these
      data do not appear to support the preferential use of BSLT for younger patients
      with pulmonary fibrosis.

PMID- 15734413
TI  - Current surgical intervention for pulmonary tuberculosis.
AB  - BACKGROUND: Surgery for pulmonary tuberculosis now plays a role in facing the
      emergence of complicated and multidrug resistant tuberculosis (MDR-TB), and it
      still remains a challenge for thoracic surgeons. We report on our 16 years of
      experience with lung resection for pulmonary tuberculosis. METHODS: We
      retrospectively reviewed the surgical results of 35 patients (23 males and 12
      females: mean age, 47.8 years) who underwent therapeutic surgical resection for
      pulmonary tuberculosis from 1988 to 2003. RESULTS: Indications for surgery were
      MDR-TB in 26 patients, hemoptysis in 7, destroyed lung in 1, and drug allergy in
      1. Thirty patients (85.7%) had fibrocavitary lesions seen radiologically, and 16
      (61.5%) MDR-TB patients showed sputum-positive preoperatively. Operative
      procedures included 22 lobectomies, 7 pneumonectomies, 5 lobectomy plus
      segmentectomy procedures, and 1 segmentectomy. There was one operation-related
      death (2.9%) and 5 major postoperative complications (14.3%). Overall, 32 of 35
      (91.4%) patients including 23 of 26 (88.5%) of the MDR-TB patients remained free
      of TB following surgery. Preoperative comorbidity, Aspergillus coinfection,
      operation time, transfusion, and male were the factors shown to be predictive of
      an unfavorable outcome. CONCLUSIONS: Surgery remains a crucial adjunct to medical
      therapy for the treatment of MDR-TB and medical failure lesions. Treatment
      success was obtained in cases with MDR-TB with few and incomplete sensitive
      drugs, and the early morbidity and mortality were acceptable in the current
      series. Proper selection of the patients and early decision for surgical
      intervention can achieve a high success rate and the salvage of lung parenchyma
      in this difficult group of patients.

PMID- 15734414
TI  - Surgical treatment of tuberculous abscess in the chest wall.
AB  - BACKGROUND: We reviewed surgical cases of tuberculous abscess in the chest wall
      and analyzed the indications and methods of surgery, results, perioperative
      complications, and postoperative treatment. METHODS: We retrospectively reviewed
      the records of 13 patients who underwent surgical treatment of tuberculous
      abscess in the chest wall between January 1994 and December 2003 at National
      Hospital Organization Tokyo Hospital. RESULTS: There was a past history of
      tuberculosis in 3 patients, concomitant active pulmonary tuberculosis in 5,
      concomitant active tuberculosis in the neck lymph node in 1, and no antecedent
      tuberculosis in 4. The locations of the tuberculous abscesses were right chest
      wall in 8 patients, left chest wall in 3, and anterior chest wall in 2. All of
      the patients underwent surgical treatment. In all patients, postoperative
      antituberculous treatments were administered. The combination regimens consisted
      of isoniazid (400 mg/d), rifampicin (450 mg/d), ethambutol (750 mg/d),
      pyrazinamide (1,500 mg/d), or some combination of these, and the duration ranged
      more than 6 months. Postoperative complications were not seen, and there was no
      recurrence. CONCLUSIONS: We recommend a complete resection of the abscess with
      rib resection, and postoperative treatment by tuberculous chemotherapy regimen.
      We consider that these treatments reduce postoperative recurrence.

PMID- 15734415
TI  - Comparison of morbidity, 30-day mortality, and long-term survival after
      pneumonectomy and sleeve lobectomy for non-small cell lung carcinoma.
AB  - BACKGROUND: The advantage of sleeve lobectomy as an alternative to pneumonectomy
      for preserving lung function is obvious and among other arguments allows
      operating on patients with lung cancer who would not tolerate pneumonectomy. The
      purpose of this retrospective, nonrandomized study is to compare the early (30
      day mortality) and late (5-year survival) outcomes of both procedures. METHODS:
      The charts of 310 patients who underwent either pneumonectomy or sleeve lobectomy
      for lung cancer stages I to IIIA from 1987 to 1997 were reviewed. One hundred
      ninety-four patients underwent pneumonectomy, and 116 patients underwent sleeve
      lobectomy. Specific operative complications, i.e., anastomotic leakage versus
      stump dehiscence, perioperative complications, 30-day or in-hospital mortality,
      and 5-year survival were registered for comparison of the immediate risk of the
      respective procedures. RESULTS: In the bronchial sleeve lobectomy group, the
      incidence of anastomotic leakage was 6.9% (8 of 116 patients) and the operative
      mortality was 4.3%. The incidence of bronchial stump fistulas after pneumonectomy
      was 3.6% (7 of 194 patients), and early mortality was 4.6%. All but 6 patients
      (98%) had a complete resection. Overall 5-year survival after sleeve lobectomy
      was 39% and after pneumonectomy, 27%. The distribution of 5-year survival stage
      by stage in either group is presented. Sleeve lobectomy, age younger than 65
      years, pN0, and stage I are positive prognostic factors for long-term survival.
      In the multivariate analysis, pneumonectomy is a negative prognostic factor.
      CONCLUSIONS: The indication for pneumonectomy versus sleeve lobectomy depends on
      the localization of the primary tumor on the one hand, and on cardiorespiratory
      function, which might be more often distinctly impaired in the sleeve group, on
      the other hand. This could explain why the mortality in the sleeve lobectomy
      group was identical with that in the pneumonectomy group. However, both
      techniques are appropriate treatment modalities of advanced lung cancer or
      patients with critical functional reserve. Therefore, whenever possible, sleeve
      lobectomy should be performed.

PMID- 15734416
TI  - Comparison between clinical and pathologic staging in 2,994 cases of lung cancer.
AB  - BACKGROUND: The accuracy of clinical staging in lung cancer may be evaluated by
      comparing it against the gold standard of pathologic staging. The objective of
      this paper is to compare these two staging methods in a series of 2,994 lung
      cancer cases operated on consecutively in Spain between 1993 and 1997. METHODS:
      The raw frequency of agreement was used to compare clinical against pathologic
      staging and to assess the agreement. Kappa's index was used to determine the
      random effect of agreement. RESULTS: Ninety-three percent of the entire
      population were men, with a mean age of 64 years (median, 66; SD, 9.6). The
      majority of cases were classified as squamous tumors (1,774; 59%), with complete
      resection (2,410; 80%), and with lobectomy or bilobectomy (1,490; 55%). The most
      frequently found pathologic stage was pIB (997; 37%), followed by pIIIA (524;
      19%). Considering the 2,377 cases with clinical and pathologic staging data, a
      classification coincidence was observed in 1,108 cases (47%; Kappa's index 0.248
      for stages IA through IIIB). Considering the pathologic staging as the gold
      standard, the agreement was 75% for stages IA-IB (Kappa's index 0.56). In
      general, downstaging is more frequent than upstaging. CONCLUSIONS: This recent
      series of lung cancer showed the low diagnostic accuracy of the clinical staging
      as compared with the pathologic staging. Diagnostic accuracy was found to be much
      higher in the initial IA-IB stages, as illustrated by Kappa's index.

PMID- 15734418
TI  - Lung cancer after heart transplantation: a 17-year experience.
AB  - BACKGROUND: The effects of heart transplantation on lung cancer incidence in
      heart transplant recipients are unclear. METHODS: In an observational study, we
      retrospectively reviewed the charts of all patients undergoing heart
      transplantation at our institution from July 1982 to July 1999. Data on lung
      cancer incidence, risk factors, treatment, and outcome were collected. RESULTS:
      Five hundred seventy-two patients (mean age, 50 +/- 11 years; range, 18 to 73)
      were considered at risk for lung cancer. Of these, 324 (57%) had a more than 20
      pack-year history of smoking before transplantation. Lung cancer developed in 2
      patients 1 year or less after transplantation and in 8 patients more than 1 year
      after transplantation (incidence, 2.2 per 1,000 patients per year of follow-up).
      Non-small cell lung cancer was diagnosed in all cases. Median survival was 10.8
      months (range, 2 to 37.5). Routine annual chest radiographs after transplantation
      enabled early diagnosis in 5 cases (stages Ia and IIa), which correlated with
      better mean survival (28.1 months [range, 19 to 37.5] versus 5.1 months [range, 2
      to 10.8]; p = 0.0002). CONCLUSIONS: The incidence of lung cancer in our
      population of heart transplant recipients appears to be no higher than in
      nontransplant populations with similar risk factors (ie, smoking and age).
      Routine radiographic imaging of transplant recipients may allow earlier detection
      of lung cancer and thus offer a survival benefit.

PMID- 15734419
TI  - Visual and semiquantitative analyses for F-18 fluorodeoxyglucose PET scanning in
      pulmonary nodules 1 cm to 3 cm in size.
AB  - BACKGROUND: While visual assessment is the simplest way to evaluate positron
      emission tomography (PET) with fluorodeoxyglucose (FDG), faintly positive nodules
      are often difficult to evaluate. We performed visual and semiquantitative
      analyses of pulmonary nodules from 1 to 3 cm in size to determine the optimal
      method of analysis for PET data, especially for faintly positive nodules on
      visual assessment. METHODS: Positron emission tomography data were analyzed for
      161 pulmonary nodules from 1 to 3 cm in size (108 malignant and 53 benign
      nodules). On visual assessment, FDG uptake by the nodules was classified into
      three grades in comparison with mediastinal blood pool, (ie, definitely positive,
      faintly positive, and negative). In addition, FDG uptake was measured by the
      standard uptake value (SUV), the contrast ratio to the contralateral lung (CR
      lung), and the contrast ratio to the cerebellum (CR-brain). Cut-off values for
      each variable were determined from receiver operating characteristics (ROC)
      curves, and the values were 2.5 for the SUV, 0.4 for the CR-lung, and 0.25 for
      the CR-brain. Nodules with FDG uptake above these cut-off values were defined as
      positive in each method. RESULTS: Visual assessment showed definitely positive
      for 80 nodules (64 malignant and 16 benign), faintly positive for 22 (17
      malignant and 5 benign), and negative for 59 nodules (27 malignant and 32
      benign). In the 139 nodules that were definitely positive or negative by visual
      assessment, there were no significant differences of sensitivity and specificity
      among the four methods (visual assessment, SUV, CR-lung, and CR-brain). In the 17
      malignant nodules that were faintly positive, the SUV did not detect any true
      positive nodules, but the CR-lung and CR-brain showed 9 and 5 true-positive
      nodules, respectively, resulting in a significantly higher sensitivity than the
      SUV (p < 0.001 and p = 0.02, respectively). Fifteen of 17 faintly positive
      malignant nodules (88%) were histologically well- or moderately-differentiated
      adenocarcinoma. CONCLUSIONS: The semiquantitative methods (SUV, CR-lung, and CR
      brain) do not improve the efficacy of visual assessment alone for nodules graded
      as definitely positive or negative. However, faintly positive nodules on visual
      assessment should be evaluated by the CR-lung or CR-brain rather than the SUV,
      and are often differentiated adenocarcinomas.

PMID- 15734421
TI  - Surgically induced accelerated local and distant tumor growth is significantly
      attenuated by selective COX-2 inhibition.
AB  - BACKGROUND: Even after apparently curative resection, lung cancer recurrence
      continues to lead to high mortality levels. The aim of this study was to assess
      the effects of cyclooxygenase-2 (COX-2) inhibitor on local and systemic recurrent
      tumor growth. METHODS: C57BL/6 mice underwent mammary fat pad inoculation with
      3LL cells. After two weeks growth, flank tumors were resected completely and
      followed for recurrent tumor growth. Postresection mice were randomized to
      receive placebo alone (group 1) or the selective COX-2 inhibitor, rofecoxib
      (group 2), daily for two weeks by tube feeding. Recurrent tumor growth kinetics
      were compared for both groups. Two weeks following primary tumor excision animals
      were sacrificed, after which lungs were resected and pulmonary metastatic burden
      was assessed using the lung-body weight ratio. Apoptotic and mitotic indices were
      established for recurrent tumors and lungs, using hematoxylin and eosin
      histology. RESULTS: Two weeks postexcision of the primary tumor, recurrent tumors
      in the placebo group were significantly greater than the treatment group (p =
      0.002). While primary tumors were typically encapsulated and not adherent,
      recurrent tumors in the placebo group were invasive, adherent to the chest wall
      and the overlying wound. In contrast, recurrent tumors in the treatment group
      were nonadherent to the chest wall. Moreover, postoperative pulmonary metastatic
      burden was significantly reduced in treated animals. Histologic examination
      revealed increased apoptosis as well as an increase in the apoptosis-mitosis
      ratio in treated animals. CONCLUSIONS: Primary tumor excision was associated with
      accelerated local and systemic tumor recurrence. However, these effects were
      significantly attenuated using selective COX-2 inhibition. The COX-2-inhibition
      was associated with increased levels of apoptosis. These findings endorse a role
      for COX-2 inhibition in the secondary prevention of lung cancer recurrence at
      both local and systemic levels.

PMID- 15734422
TI  - Can we predict long-term survival after pulmonary metastasectomy for renal cell
      carcinoma?
AB  - BACKGROUND: The purpose of this study is to identify factors associated with time
      related survival after pulmonary metastasectomy for renal cell carcinoma and to
      confirm the safety of metastasectomy. METHODS: From January 1986 to July 2001,
      417 patients were diagnosed with pulmonary metastases from renal cell carcinoma;
      92 underwent pulmonary metastasectomy. Median disease-free interval after
      nephrectomy was 3.0 years. Half the patients had 1 or 2 pulmonary nodules; 37%
      had 5 or more. Median size of the largest nodule (pulmonary metastasis) was 15
      mm. Complete resection was obtained in 63 patients (68%). Twenty-nine patients
      received preoperative immunotherapy. Multivariable hazard function analysis was
      used to identify continuous, ordinal, and true dichotomous risk factors. RESULTS:
      PREDICTORS: The strongest risk factor for time-related mortality was incomplete
      resection. Five-year survival was 8% for incomplete and 45% for complete
      resection. Other risk factors included the following continuous and ordinal
      variables: larger nodule size (p = 0.0001), increasing number of involved lymph
      nodes (p = 0.01), and decreased preoperative 1-second forced expiratory volume (p
      = 0.02). Immunotherapy did not improve survival. For completely resected
      patients, shorter disease-free interval was a risk factor (p = 0.01). Fewer
      pulmonary nodules predicted higher probability of complete resection (p <
      0.0001). SAFETY: No operative deaths occurred. Nine patients (10%) experienced a
      total of 12 complications, with persistent air leak and atrial arrhythmia
      accounting for 5 (42%). CONCLUSIONS: Because pulmonary metastasectomy for renal
      cell carcinoma is safe, survival depends on complete resection of pulmonary
      disease and adequate pulmonary reserve. Preoperative determination of
      resectability is thus critical, and computed chest tomography and mediastinoscopy
      are valuable tools for optimizing patient selection.

PMID- 15734423
TI  - Factors associated with postoperative delirium after thoracic surgery.
AB  - BACKGROUND: Postoperative delirium is an acute confusional state characterized by
      fluctuating consciousness and is associated with increased morbidity and
      mortality. We analyzed the incidence and risk factors of delirium following
      thoracic surgery. METHODS: All patients (n = 432) who underwent thoracotomy or
      sternotomy from 1996 to 2003 were analyzed retrospectively. The diagnosis of
      postoperative delirium was based on Diagnostic and Statistical Manual of Mental
      Disorders- IV criteria. RESULTS: Postoperative delirium developed in 23 patients
      (5.32%) between postoperative days 2 to 12 (mean, 4.4 +/- 2.6 days). There were
      15 males and 8 females, with a mean age of 59.4 years (24 to 77 years). The
      delirium group was older (59.4 +/- 14.6 vs 51.3 +/- 15.5 years, p < 0.01) and had
      a longer operation time than the nondelirious group (5.34 +/- 1.58 vs 4.38 +/-
      1.6 hours, p = 0.005). Morbidity and mortality rates were not significantly
      different between the two groups (56.5% vs 47.1%; 13.0% vs 3.66%, respectively).
      Univariate analysis showed that the older age, markedly abnormal postoperative
      levels of sodium, potassium, or glucose, sleep deprivation, operation time, and
      diabetes mellitus were risk factors (p < 0.05). According to multivariate
      analyses, four factors were selected as predictive risk factors: (1) markedly
      abnormal postoperative levels of sodium, potassium, or glucose (p = 0.038); (2)
      sleep deprivation (p = 0.05); (3) age (p = 0.033); and (4) operation time (p =
      0.041). CONCLUSIONS: Postoperative delirium may cause higher morbidity and
      mortality rates after thoracic surgery. Close postoperative follow-up and early
      identification of predisposing factors such as older age, sleep deprivation,
      abnormal postoperative levels of sodium, potassium, or glucose, and longer
      operation time can prevent occurrence of postoperative delirium.

PMID- 15734424
TI  - Cyclosporine modulates the response to hypoxia-reoxygenation in pulmonary artery
      endothelial cells.
AB  - BACKGROUND: Depletion of macrophages, neutrophils, or lymphocytes confers only
      partial protection against experimental lung reperfusion injury, suggesting that
      inflammatory responses in other cell types contribute to tissue injury.
      Endothelial cell activation has previously been shown to be critical to the
      development of ischemia-reperfusion injury in other vascular beds. Furthermore,
      cyclosporine (CSA) reduces in vivo lung reperfusion injury through attenuated
      secretion of proinflammatory mediators. These studies determined whether
      pulmonary artery endothelial cells (PAEC), subjected to hypoxia and
      reoxygenation, promote inflammation and whether CSA afforded any modulation of
      that response. METHODS: Isolated rat PAEC were subjected in vitro to 2 hours
      hypoxia followed by up to 4 hours reoxygenation. Cells were pretreated with CSA
      or a cremaphor vehicle. Differences in activation of signaling kinases and
      transcription factors were assessed, as was cytokine-chemokine protein secretion.
      RESULTS: There was significant signaling kinase (extracellular signal regulated
      kinase [ERK 1/2]) activation by 15 minutes reoxygenation, which was temporally
      associated with marked activation of the transcription factors nuclear factor
      kappa B (NFkappaB) and early growth response one (EGR-1). At 4 hours
      reoxygenation there were significant increases in chemokine protein secretion.
      The CSA decreased ERK 1/2 phosphorylation and significantly attenuated
      transcription factor transactivation at 15 minutes reoxygenation. The CSA was
      found to be selective in reducing cytokine-chemokine elaboration at 4 hours
      reoxygenation. CONCLUSIONS: Hypoxia-reoxygenation induces ERK 1/2
      phosphorylation, as well as transactivation of the transcription factors NFkappaB
      and EGR-1 in PAEC. Cyclosporine selectively reduces proinflammatory mediator
      secretion, likely by transcriptional regulation through NFkappaB and EGR-1. This
      is the first demonstration of ERK 1/2 inhibition afforded by CSA.

PMID- 15734425
TI  - Automatic intraaortic balloon pump timing using an intrabeat dicrotic notch
      prediction algorithm.
AB  - PURPOSE: The efficacy of intraaortic balloon counterpulsation (IABP) during
      arrhythmic episodes is questionable. A novel algorithm for intrabeat prediction
      of the dicrotic notch was used for real time IABP inflation timing control.
      DESCRIPTION: A windkessel model algorithm was used to calculate real-time aortic
      flow from aortic pressure. The dicrotic notch was predicted using a percentage of
      calculated peak flow. Automatic inflation timing was set at intrabeat predicted
      dicrotic notch and was combined with automatic IAB deflation. EVALUATION:
      Prophylactic IABP was applied in 27 patients with low ejection fraction (< 35%)
      undergoing cardiac surgery. Analysis of IABP at a 1:4 ratio revealed that IAB
      inflation occurred at a mean of 0.6 +/- 5 ms from the dicrotic notch. In all
      patients accurate automatic timing at a 1:1 assist ratio was performed. Seventeen
      patients had episodes of severe arrhythmia, the novel IABP inflation algorithm
      accurately assisted 318 of 320 arrhythmic beats at a 1:1 ratio. CONCLUSIONS: The
      novel real-time intrabeat IABP inflation timing algorithm performed accurately in
      all patients during both regular rhythms and severe arrhythmia, allowing fully
      automatic intrabeat IABP timing.

PMID- 15734427
TI  - Facilitated minimally invasive left ventricular epicardial lead placement.
AB  - PURPOSE: Atrial-synchronized biventricular pacing is an effective treatment
      option in patients with heart failure and interventricular conduction delay.
      Owing to a failed transvenous implantation in some patients, the left ventricular
      (LV) lead has to be placed surgically, usually by an anterolateral thoracotomy.
      We used a novel malleable epicardial lead placement tool (Epicardial Lead Implant
      Tool, Model 10626; Medtronic, Minneapolis, MN) that facilitates lead placement on
      the posterior aspect of the LV through an anterolateral minithoracotomy.
      DESCRIPTION: The tool consists of a malleable steel shaft with distal gripping
      tongs for the epicardial lead. Proximally, a thumbwheel and an actuator button
      allow fixation and release of the lead on the myocardium. EVALUATION: We used
      this tool in 7 patients through an anterolateral minithoracotomy. All patients
      had a safe, successful, and rather short procedure. No scopes were required.
      CONCLUSIONS: Epicardial LV lead placement through an anterolateral
      minithoracotomy is facilitated by using the Lead Implant Tool. Lead placement is
      achieved by the malleable shaft design, which enables perpendicular implantation
      of the lead pad on the posterior LV surface with an anterolateral approach.

PMID- 15734429
TI  - Palmar microcirculation after harvesting of the radial artery in coronary
      revascularization.
AB  - PURPOSE: To evaluate real-time parameters of palmar microcirculation before and
      after harvesting of the radial artery in coronary revascularization using a laser
      Doppler flowmetry and remission spectroscopy system (O2C). DESCRIPTION: Fifteen
      patients (11 males, 54 +/- 4 years, mean New York Heart Association [NYHA] class
      of 2.3 +/- 0.3) were prospectively scheduled with control measurements of the
      fingertips of D1, D3, and D5 at base line, after suprasystolic, and after
      selective radial or ulnar compression for tissue oxygen saturation (SO2),
      postcapillary venous recombinant hemoglobin (rHb) concentration, superficial (2
      mm) blood flow, and deep (8 mm) blood flow. EVALUATION: Preoperatively during
      suprasystolic compression SO2 decreased significantly for the fingertips of D1,
      D3, and D5 by -58%, -74%, and -63%, respectively (p < 0.05). Radial compression
      reduced SO2 for all fingertips (-12%, -14%, and -16%), as did ulnar compression (
      24%, -18%, and -10%). rHb did not change significantly for either compression
      type. Superficial and deep blood flow decreased significantly after suprasystolic
      and only slightly after radial and ulnar compression at either side. No side
      differences were noted. After radial artery harvesting, microcirculatory
      parameters did not change considerably versus preoperatively. CONCLUSIONS: Radial
      artery harvesting does not remarkably change microcirculatory parameters of the
      hand. The O2C system is a safe and quantitative method to assess both
      preoperatively and postoperatively the palmar microcirculation and therefore adds
      further functional clinical information.

PMID- 15734431
TI  - Submitral left ventricular pseudoaneurysm.
AB  - We describe a successful transatrial repair in a patient with left ventricular
      pseudoaneurysm in the submitral position after a myocardial infarct.

PMID- 15734432
TI  - Successful outcome of emergency coronary artery bypass grafting and retrieval of
      entrapped stent, angioplasty balloon, and guidewire.
AB  - A 42-year-old man presented with worsening of angina after a recent angioplasty
      and stenting. Repeat angiography revealed further untreated lesions in the left
      anterior descending coronary artery. The patient underwent re-angioplasty and
      stenting. After stent deployment, the guidewire and balloon got entrapped in the
      left anterior descending coronary artery, which was associated with hypotension
      and ischemic changes of the anterolateral wall on electrocardiogram. The patient
      was stabilized with the insertion of an intraaortic balloon pump, and he
      underwent emergency coronary artery bypass grafting and removal of the entrapped
      equipment. He had an uneventful postoperative recovery.

PMID- 15734433
TI  - Traumatic innominate artery aneurysm 26 years after stab injury.
AB  - We report the case history of a 46-year-old African man with a false aneurysm of
      the innominate artery subsequent to a stab wound in the right supraclavicular
      area 26 years previously, presenting with stridor.

PMID- 15734434
TI  - Antihuman factor V antibodies after use of relatively pure bovine thrombin.
AB  - Although bovine thrombin is commonly used in the operating room, there is
      evidence that exposure to bovine thrombin can result in the development of
      autoimmune antibodies, usually against factor V, which can lead to a profound
      coagulopathy. It is thought that impurities in bovine thrombin preparations are
      responsible for the adverse reactions in patients. Here we describe a case in
      which exposure to a relatively pure bovine thrombin preparation resulted in the
      development of an antihuman factor V antibody-associated coagulopathy. This
      report calls into question the safety of even relatively pure bovine thrombin.

PMID- 15734435
TI  - Compression of trachea and left main bronchus by arch aneurysm.
AB  - We report on the case of a 70-year-old woman who presented dyspnea. Contrast
      enhanced computed tomography of the chest revealed the compression of the lower
      part of the trachea and left main bronchus by an aneurysm of the ascending aorta
      and aortic arch. Although we performed a replacement of the ascending aorta and
      aortic arch, we were unable to relieve the stenosis of the trachea and bronchus.
      By the suspension of the posterior wall of the native aneurysm, we were able to
      successfully relieve the compression and alleviate the respiratory insufficiency.

PMID- 15734436
TI  - Cardiac lymphoma following mitral valve replacement.
AB  - A primary cardiac lymphoma was encountered in a patient with prosthetic mitral
      valve dysfunction. Although rare, this tumor could be related to the presence of
      prosthetic material and specifically that of Dacron. Primary cardiac tumors have
      to be considered in the differential diagnosis of prosthetic valve dysfunction.

PMID- 15734437
TI  - Successful single-lung fontan operation in an adult: 5-year follow-up.
AB  - We report a case of a 20-year-old man with a functional single left ventricle who
      underwent a successful Fontan operation into a single left pulmonary artery, the
      right pulmonary artery being atretic. The literature of a single-lung Fontan
      procedure is also reviewed.

PMID- 15734438
TI  - One-stage unifocalization and palliative right ventricular outflow tract
      reconstruction.
AB  - We report a successful case of one-stage unifocalization concomitant with
      palliative right ventricular outflow tract reconstruction for pulmonary atresia
      and ventricular septal defect with major aortopulmonary collateral arteries and
      central pulmonary arterial absence. Through a median sternotomy, one-stage
      unifocalization was accomplished using autologous pericardial conduit and no
      prosthetic material. To achieve an adequate pulmonary blood flow, the right
      ventricular outflow tract was reconstructed so that it would be 70% of the normal
      pulmonary annular diameter, while the ventricular septal defect was left open.
      One-stage unifocalization concomitant with palliative right ventricular outflow
      tract reconstruction is considered to be a good surgical option for selected
      patients with these diseases.

PMID- 15734439
TI  - Alternative Fontan connection for apicocaval juxtaposition.
AB  - We present an alternative technique to the modified Fontan procedure used in a 3
      year-old boy who had complex heart defects with bilateral superior vena cava and
      apicocaval juxtaposition. The left superior vena caval pathway was used behind
      the ventricle to connect the inferior vena cava to the pulmonary artery. We
      proved the technical feasibility of this with good midterm results at the 5-year
      follow-up angiography.

PMID- 15734440
TI  - Bilateral minithoractomy repair of aortic coarctation with ventricular septal
      defect and persistent ductus arteriosus.
AB  - A 6-year-old female child with aortic coarctation, a ventricular septal defect,
      and a persistent ductus arteriosus underwent surgical repair by bilateral
      minithoracotomies. At 6-month follow-up, the patient had recovered well, with
      increased exercise tolerance. Transthoracic echocardiography revealed an intact
      ventricular septum and no significant gradient across the aortic repair.

PMID- 15734441
TI  - Living-donor lobar lung transplantation for bronchiolitis obliterans after bone
      marrow transplantation.
AB  - We report a successful case of living-donor lobar lung transplantation (LDLLT)
      for severe bronchiolitis obliterans (BO) after bone marrow transplantation (BMT).
      The patient is a 29-year-old woman who underwent BMT because of aplastic anemia
      in 1995. In 1996, BO developed in the patient because of chronic graft-versus
      host disease. In May 2000, a LDLLT was performed. Pulmonary function tests showed
      improvement of both vital capacity and forced expiratory volume in 1 second. At
      present, 91 months after BMT and 38 months after lung transplantation, the
      patient is in good health. LDLLT may offer a therapeutic option for the treatment
      of BO after BMT.

PMID- 15734442
TI  - Resection of a thoracic duct lymphangioma using video-assisted thoracoscopic
      surgery.
AB  - Thoracic duct lymphangioma is a rare mediastinal tumor. Most patients are
      asymptomatic. Symptoms may include dysphagia, dyspnea, cough, or chest pain.
      Workup may include chest computed tomography or lymphangiography, or both.
      Surgery should be considered the treatment of choice. We present a 60-year-old
      man with a 2.4-cm mass in the retro-cardiac space to the right of the esophagus.
      The patient underwent a thoracoscopic resection of the mass with ligation of the
      thoracic duct. We conclude that video-assisted thoracoscopic surgery allows for
      safe evaluation and resection of mediastinal pathology.

PMID- 15734443
TI  - Candida infection in a stent inserted for tracheal stenosis after heart lung
      transplantation.
AB  - Although there are many reports on the use of expandable metallic stents for
      treating an airway stenosis that develops after heart lung transplantation,
      complications from using these stents are rarely reported. We experienced a case
      of Candida infection in a stent that was placed to treat a tracheal stenosis
      after heart lung transplantation in an 11-year-old girl. The patient had
      progressive shortness of breath developed from the 5th postoperative week. Chest
      computed tomography and bronchoscopy revealed a stenosis at the level of the
      anastomosis. After repeated unsuccessful trials of endoscopic ablation of the
      granuloma, a Palmaz metallic expandable stent (8 x 30 mm) (Johnson and Johnson
      Interventional Systems Co, Warren, NJ) was placed, which was followed by
      immediate relief of the dyspnea. Bronchoscopy conducted immediately after the
      stent placement showed a free floating distal stent end, which needed to be
      followed up. The patient had been doing well for the next 9 months after stent
      placement when she again had shortness of breath develop. Endoscopic examination
      revealed an intraluminally growing fungal mass, which was particularly severe at
      the distal free edge of the stent. The culture yielded Candida albicans.
      Aggressive antifungal agents and surgical removal of the stent were planned, but
      the patient died 1 day after admission.

PMID- 15734444
TI  - Recalcitrant chest wall Aspergillus fumigatus osteomyelitis after coronary artery
      bypass grafting: successful radical surgical and medical management.
AB  - This report describes a 62-year-old male diabetic patient with persistent chest
      wall osteomyelitis that developed after repeat coronary artery bypass grafting.
      The chronic infection was localized to the right anterior chest wall and
      refractory to medical and surgical treatment including long-term antiobiotics,
      five separate intraoperative debridements, and reconstruction with vascularized
      omentum over a two-year period at outside institutions. Aggressive surgical
      debridement with flap reconstruction resulted in definitive management. The
      organism isolated from multiple intraoperative bone, cartilage, and tissue
      cultures yielded Aspergillus fumigatus; therapy with itraconazole was utilized
      for 6 months. Surgical management of osteomyelitis and costochondritis is
      reviewed accompanied by a literature review on this uncommon cause of chronic
      chest wall infection.

PMID- 15734445
TI  - Successful surgical treatment of aortoesophageal fistula after esophagectomy.
AB  - We report a 65-year-old man with complications of aortoesophageal fistula after
      esophagectomy. A combined middle-lower esophagectomy with remnant gastrectomy was
      performed for esophageal cancer. The alimentary tract was restored by
      intrathoracic esophagojejunal anastomosis using a surgical stapler. Twenty-four
      days later the patient suddenly had hypovolemic shock develop due to
      aortoesophageal fistula. We performed emergency surgery, and the aortic fistula
      was directly closed with a 3-0 monofilament using abdominal fascia as a pledget.
      Thirty-eight days later, alimentary reconstruction was performed using a free
      jejunal graft. Aortic pseudoaneurysm due to direct closure was predictably
      detected, and transluminal endovascular stent grafting was indicated.

PMID- 15734446
TI  - Hemodynamic compromise from a right coronary artery pseudoaneurysm after remote
      stent placement.

PMID- 15734447
TI  - Plombage thoracoplasty with Lucite balls.

PMID- 15734448
TI  - A new device for ensuring the correct length of artificial chordae in mitral
      valvuloplasty.
AB  - Mitral valvuloplasty using Gore-Tex as artificial chordae, especially for
      patients with anterior leaflet prolapse, is often associated with difficulties in
      determining the length of artificial chordae as well as in preventing knot
      slipping. We describe a simple technique of using a new device that enables
      surgeons to easily determine the accurate length of the artificial chordae and to
      tie the slippery knot without sliding and damaging it.

PMID- 15734449
TI  - D-transposition of the great arteries with an aortopulmonary window: a new
      corrective technique.
AB  - D-transposition of the great arteries with an aortopulmonary window is rare. Five
      cases have been previously reported. Arterial switch is the procedure of choice.
      We describe a new method of transferring coronaries making use of the
      aortopulmonary window and a pericardial patch to form a pouch.

PMID- 15734450
TI  - How to tailor A "pi" graft for complex myocardial revascularization: a variant of
      the mammary loop technique.
AB  - We present a new pattern for tailoring the "pi" graft that uses the advantages of
      the mammary loop technique. The two internal thoracic mammary arteries are
      skeletonized. The free right mammary artery is anastomosed end-to-side to the
      proximal part of the in situ left mammary artery to make a "Y" graft. The distal
      end of the left mammary artery is anastomosed end-to-side to the middle portion
      of the right one to form a loop with the two arteries. The loop is severed at the
      appropriate level at the time of the coronary anastomosis to form a "pi" graft.
      This technique allows a more rational use of the length of the two mammary
      arteries, because the branch leading to the left anterior descending artery is
      measured and cut precisely at the time of the anastomosis.

PMID- 15734451
TI  - A simple and effective method of preventing inadvertent occlusion of chest tube
      drains: the corrugated tubing splint.
AB  - Inadvertent occlusion of tube thoracostomy drains by normal patient positioning
      can be not only a nuisance but also a potentially life-threatening problem. A
      method of splinting the pliable chest tube drains by using corrugated ventilator
      circuit tubing is described. This relatively simple and quick technique can help
      to prevent this undesired and potentially dangerous occlusion of chest tube
      drains.

PMID- 15734452
TI  - Calcification of tissue heart valve substitutes: progress toward understanding
      and prevention.
AB  - Calcification plays a major role in the failure of bioprosthetic and other tissue
      heart valve substitutes. Tissue valve calcification is initiated primarily within
      residual cells that have been devitalized, usually by glutaraldehyde
      pretreatment. The mechanism involves reaction of calcium-containing extracellular
      fluid with membrane-associated phosphorus to yield calcium phosphate mineral
      deposits. Calcification is accelerated by young recipient age, valve factors such
      as glutaraldehyde fixation, and increased mechanical stress. Recent studies have
      suggested that pathologic calcification is regulated by inductive and inhibitory
      factors, similar to the physiologic mineralization of bone. The most promising
      preventive strategies have included binding of calcification inhibitors to
      glutaraldehyde fixed tissue, removal or modification of calcifiable components,
      modification of glutaraldehyde fixation, and use of tissue cross linking agents
      other than glutaraldehyde. This review summarizes current concepts in the
      pathophysiology of tissue valve calcification, including emerging concepts of
      endogenous regulation, progress toward prevention of calcification, and issues
      related to calcification of the aortic wall of stentless bioprosthetic valves.

PMID- 15734453
TI  - Role of angiotensin-converting enzyme inhibitors in the coronary artery bypass
      patient.
AB  - Angiotensin-converting enzyme inhibitors have been shown to prolong survival and
      decrease infarct size in patients after acute coronary syndromes. Now there is
      evidence to suggest that angiotensin-converting enzyme inhibition is beneficial
      in coronary artery bypass patients. This review will summarize the beneficial
      effects of angiotensin-converting enzyme inhibition in patients with ischemic
      heart disease and provide evidence to show that the routine use of angiotensin
      converting enzyme inhibition in coronary artery bypass patients can improve
      clinical outcomes.

PMID- 15734454
TI  - Transesophageal echocardiography for pulmonary embolectomy.

PMID- 15734456
TI  - The third option.

PMID- 15734457
TI  - Arterial pressure and pump flow rate during long-term pulsatile and nonpulsatile
      cardiac support.

PMID- 15734461
TI  - MCC-135 diminishes the egress of CK-MB but not of troponin-I from cardiomyocytes
      during reperfusion.

PMID- 15734462
TI  - Parasternal wire technique and sternal dehiscence.

PMID- 15734464
TI  - Markers of endothelial activation during cardiopulmonary bypass.

PMID- 15734465
TI  - Mediastinal parathyroid adenoma.

PMID- 15734466
TI  - Total aortic arch replacement.

PMID- 15734467
TI  - Should all stage-one Norwood patients receive a prolonged period of postoperative
      mechanical circulatory support?

PMID- 15734468
TI  - Simultaneous bilateral apical bullectomy through access from only one side.

PMID- 15734469
TI  - Lymphangiomatosis possibly With Gorham's disease and not lymphangioma.

PMID- 15734472
TI  - The distinct and secondary harmful effect of pelvic and extremity injury on the
      outcome of laparotomy for trauma.
AB  - HYPOTHESIS: Extra-abdominal injury negatively affects the outcome of abdominal
      injury following trauma laparotomy. DESIGN: Retrospective review of 920
      consecutive patients receiving laparotomy for trauma who survived more than 24 h
      between January 1989 and May 1998 at a Level 1 trauma center. Major abdominal
      complications (MAC) were defined as: abdominal compartment syndrome (ACS),
      abscess/peritonitis, enterocutaneous fistula, necrotizing fasciitis, and
      necrotizing pancreatitis. METHODS: Univariant and multivariant logistic
      regression were used to identify predictors of MAC. RESULTS: Sixty-nine patients
      (7.5%) developed one or more MAC. Patients who developed MAC had higher injury
      severity scores (ISS), abdominal trauma indices (ATI), and blood transfusions in
      the first 24 h (PRCs) than patients who did not develop MAC. Patients with MAC
      were more likely to have suffered a thoracic or pelvic injury with an abbreviated
      injury scale (AIS) > or =3 and were more likely to have received an extremity
      injury (AIS > or =3) operation than patients without MAC. Independent predictors
      of MAC in multivariant analysis included colon injury (AIS > or =3) [odds ratio
      (OR) = 3.1, 95% confidence interval (CI) 1.5- 6.3)], pelvic injury (AIS > or =3)
      or operation for extremity injury (AIS > or =3) [OR 2.9, 95% CI 1.5-5.3], and ATI
      (OR = 1.03 for each 10 unit increase in ATI, 95% CI 1.02-1.05). PRCs did not
      independently predict MAC. CONCLUSION: The outcome of laparotomy for trauma (both
      blunt and penetrating) is negatively affected by a severe pelvic injury or a
      severe extremity injury operation independent of initial hemorrhage and abdominal
      injury severity.

PMID- 15734473
TI  - Ornithine breath test as a method to evaluate functional liver volume.
AB  - BACKGROUND: The purpose of this study was to investigate whether the functional
      liver volume can be measured from changes in expiratory 13CO2 levels after
      intravenous administration of L-[1, 2-13C] ornithine, using a rat model of
      hepatectomy. MATERIALS AND METHODS: Under pentobarbital anesthesia, 30%, 70%, or
      90% hepatectomy was performed. In the control group, simple laparotomy was
      performed. Then, 20 mg/kg L-[1, 2-13C] ornithine was administered to rats via the
      femoral vein. A breath test was conducted 20 min after laparotomy. We examined
      the correlation of the sum of 13CO2 output (S) or a single point of 13CO2 level
      (SP) with liver weight/body weight (LW/BW) (%) every 15 min. RESULTS: In all of
      the groups, the ornithine breath test (OBT) graph reached a plateau level at
      about 6 min. The correlation coefficient between S15 and LW/BW was highest 0.952
      (P <0.0001). The correlation coefficient between SP14 and LW/BW was highest,
      0.944 (P <0.0001). The severity of hepatic injury could be evaluated, with
      significant differences in S5-15 and SP5-15 in all comparisons between groups.
      CONCLUSION: In the breath test with intravenously administered L-[1, 2-13C]
      ornithine, functional liver volume could be evaluated accurately in a short
      period.

PMID- 15734474
TI  - Persistent vascular defects in lung allografts attributed to defective endogenous
      endothelial progenitors.
AB  - BACKGROUND: A major pathological finding in human newborns with pulmonary
      hypoplasia and congenital diaphragmatic hernia is the presence of vascular
      abnormalities in lungs. Vasculogenesis/angiogenesis are crucial to lung
      development. To study lung alveolar development, including microvascular
      formation in fetal lung implants, Schwarz et al. [1] developed a subcutaneous
      allograft model. We adopted their model to assess the influence of
      neovascularization or the "host-graft vascular development" on hypoplastic lung
      structure and growth. MATERIALS AND METHODS: Normal and hypoplastic lungs at
      pseudoglandular stage were implanted subcutaneously under the dorsolateral fold
      of immunocompromised nude mice (athymic, nu/nu). Lung allografts were removed and
      assessed at 2, 4, 6, and 8 weeks postimplantation. RESULTS: Neovascularization of
      implanted lungs from subcutaneous vasculature of nude mice resulted in varying
      degrees of maturation of implanted normal and hypoplastic lungs. By 4 weeks,
      implanted normal lungs contained Type 2-like cells and by 7 to 8 weeks, Type 2
      and Type 1-like cells, air spaces had enlarged, and surfactant secretion was
      observed. Despite some differentiation and maturation of hypoplastic lungs, there
      was more mesenchymal tissue, no secondary septa, and smaller air spaces compared
      to normal lungs. CONCLUSIONS: (a) Neovascularization or host-graft vascular
      development occurs in both normal and hypoplastic lung allografts. (b)
      Development and maturation of implanted normal and hypoplastic lungs follow the
      establishment of the vascular connections between the host and grafts. (c) The
      host-graft vascular connections do not improve the growth of normal or
      hypoplastic lungs. (d) Neovascularization failed to overcome the embryonic
      defects in vascular formation and the pulmonary vasculogenesis remained defective
      in hypoplastic lung allografts, which may be attributed to the defective
      endogenous endothelial progenitor cells.

PMID- 15734475
TI  - Lipid metabolism in omental adipose tissue during operative surgery.
AB  - BACKGROUND: Omental adipose tissue is a pure depot of visceral adipose tissue. We
      investigated the regulation of lipid metabolism in human omental tissue in vivo
      by the arterio-venous technique. MATERIALS AND METHODS: Six adults were studied
      while undergoing elective colonic surgery. Their omental vein was cannulated
      intraoperatively, and after obtaining the baseline blood samples, 50 ml of 50%
      dextrose solution was given intravenously and simultaneous arterio-venous samples
      were taken for the next 2 h. Concentration differences of lipid metabolites,
      glucose, and lactate were measured across the arterio-venous bed. The rates of
      action of hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) were
      calculated by stoichiometric analysis and the rate of re-esterification of
      nonesterified fatty acids (NEFA) was determined. RESULTS: After an overnight fast
      there was a significant release of NEFA and glycerol from the omental adipose
      tissue (P <0.05, P <0.05). Intravenous glucose load caused a significant
      reduction in the arterial NEFA and glycerol concentrations (P <0.05, P <0.05),
      but only the arterio-venous concentration of NEFA decreased significantly (P
      <0.05). There was no significant change in the arterio-venous concentration
      difference of glycerol, and the relative rate of action of HSL decreased, but not
      significantly (P=0.09 at 30 min; P=0.054 at 120 min). The ratio of release of
      NEFA to glycerol changed significantly (ANOVA; P <0.05) from 2.93:1 to 0.1:1.
      CONCLUSION: The net release of NEFA by omental adipose tissue is primarily
      regulated by their local re-esterification. The change in the rate of action of
      HSL and LPL plays a minor role in the net release of NEFA by omental adipose
      tissue.

PMID- 15734476
TI  - Hepatic CCR7lowCD62LlowCD45RClow allograft dendritic cells migrate to the splenic
      red pulp in immunologically unresponsive rats.
AB  - Donor dendritic cells (DC) migrate into the recipient spleen after hepatic
      transplantation. Immunological unresponsiveness to rat hepatic allografts can be
      induced by prior donor-specific blood transfusion (DST). We investigated homing
      receptor phenotype and splenic distribution of donor DC after allografting and
      DST. Immunostaining revealed OX62+ cells in the splenic red pulp of animals
      receiving pre-transplant DST but only in the white pulp of untreated animals.
      Most OX62 cells were positive for OX76. There were two subsets of DC in the
      spleen, CD45RChighOX62+ and CD45RClowOX62+ cells. RT-PCR revealed that
      CD45RClowOX62+ cells expressed interleukin (IL)-10, while CD45RChighOX62+ cells
      expressed IL-2 and low levels of IL-10 mRNA. CD45RChighOX62+ cells strongly
      expressed CCR5 and CCR7, compared with weak expression in CD45RClowOX62+ cells.
      The Epstein-Barr virus-induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3beta)
      was expressed mainly within the splenic white pulp. Mucosal vascular addressin
      cell adhesion molecule-1 (MAdCAM-1) was expressed in the marginal zone and white
      pulp, but expression of splenic MAdCAM-1 was down-regulated in DST-treated
      animals. L-selectin (CD62L), the ligand for MAdCAM-1, was strongly expressed on
      CD45RChighOX62+ cells but not on CD45RClowOX62+ cells. In conclusion,
      differential splenic migration of CCR5lowCCR7lowCD62Llow CD45RClow DC expressing
      Th2-type cytokines is associated with immunological unresponsiveness to rat
      hepatic allografts.

PMID- 15734477
TI  - Donor cell engraftment in recipient lymphoid tissues after rat limb allograft.
AB  - BACKGROUND: The movement of cells from a transplanted tissue into the host
      organs, the so-called systemic chimerism, is a phenomenon known to occur and be
      associated with the development of immunologic tolerance in allotransplantation
      cases. The purpose of this study was to identify donor cell engraftment in
      recipient lymphoid tissues after performing rat hind limb allograft. MATERIALS
      AND METHODS: Fifty-five whole-limb allotransplantations were performed in sex
      mismatched pairs of rats. Syngeneic male Lewis and allogeneic Dark Agouti donors
      were transplanted to female Lewis recipients. FK506 was used for
      immunosuppression. Donor male cells could be identified in the recipient female
      tissues by semiquantitative polymerase chain reaction analysis for a Y chromosome
      specific DNA sequence. Chimerism was assessed at 1, 24, and 48 weeks after
      transplantation. RESULTS: There was no rejection episode in any of the limb
      grafts. Although levels of chimerism were highly variable in each lymphoid
      tissue, a gradual increase was noticed in all during the course of time. At 1
      week after the transplant period, only intrasplenic chimerism was at high level
      (1%) in three groups. At 48 weeks after the transplant, all recipients with
      allografts showed very high level (10%) of chimerism in the bone marrow. Two,
      two, and two of six recipients showed very high levels in the spleen, lymph node,
      and liver, respectively, at 48 weeks. Intrathymic chimerism was higher at 24
      weeks after transplant rather than at 48 weeks. CONCLUSION: We demonstrated donor
      cell engraftment into recipient lymphoid tissues after successful whole limb
      transplantation. We conclude that limb allograft can work as a vascularized
      carrier for the bone marrow transplantation, provide a continuous source of donor
      cells and contribute to chimerism in the recipient.

PMID- 15734478
TI  - Absence of PERV infection in baboons after transgenic porcine liver perfusion.
AB  - BACKGROUND: Xenotransplantation offers great promise to supplement the shortage
      of human organs available for transplant, but cross-species infection is a
      substantial concern. Porcine endogenous retrovirus (PERV), in particular, is
      thought to pose a risk as a potential pathogen to humans. We evaluated whether
      PERV is capable of infecting nonhuman primates in vivo after extracorporeal
      porcine liver perfusion (ECLP). METHODS: Livers were harvested from six human
      decay-accelerating factor (h-DAF) transgenic piglets and perfused with fresh
      baboon blood via the portal vein and the hepatic artery. Six healthy baboons
      underwent direct cross-circulation with the ECLP for 13 to 24 h without
      immunosuppression. Peripheral blood and bone marrow of baboons were sampled
      periodically until the baboons were euthanized for the examination of various
      organ tissue samples. Genomic DNA was extracted from those samples and tested for
      PERV and pig-specific centromeric DNA sequences by quantitative PCR. Validation
      showed that the assay could detect one copy of PERV in a background of 150,000
      baboon cells, and it was quantitative over a range from 10 to 10(6) copies of
      PERV. RESULTS: PERV sequences were detected in a high number (4.4 x 10(3)-1.6 x
      10(4)/1 microg) in peripheral leukocyte DNA during the initial phases of ECLP,
      but they disappeared within 1 week. Bone marrow DNA contained PERV sequences
      longer than peripheral blood, but PERV signals became negative within 1 month. No
      PERV DNA relapse was seen over the course of this study. Pig-specific centromeric
      sequences were also detected in the same manner. At 6 months or 1 year after
      ECLP, no PERV or pig-specific centromeric sequences were detected in the genomic
      DNA obtained from the following organs: skin, lymph nodes, spleen, liver,
      pancreas, kidney, heart, and lung. CONCLUSIONS: ECLP did not result in PERV
      infection or pig-cell microchimerism in baboons.

PMID- 15734479
TI  - Exogenous nitric oxide can control SIRS and downregulate NFkappaB.
AB  - BACKGROUND: Nitric oxide (NO) participates in inflammation and affects almost all
      steps of its development. Several experimental studies have unveiled the
      beneficial effects of NO through modulation of the Systemic Inflammatory Response
      Syndrome (SIRS). In this sense, in the present work we attempted to evaluate the
      beneficial effects of exogenous NO and its levels of action (biochemical and
      cellular) in a model of SIRS induced by two sequential insults. MATERIALS AND
      METHODS: Dacron graft implantation (first insult) and subsequent administration
      of Zymosan A (second insult) in Wistar rats. The animals were divided into four
      groups: 1) No manipulation (Basal); 2) Laparotomy (L) + mineral oil (Sham); 3) L
      + Graft-Zymosan (GZ) (Control); and 4) L + GZ + NO (Assay). Determinations:
      Survival, TNF-alpha, SOA, ICAM-1, and NFkappaB. RESULTS: The model established
      (Control) induced a mortality rate of 20%. Also, it significantly increased the
      levels of TNF-alpha (P <0.001) and SOA (P <0.01), ICAM-1 expression, and NFkappaB
      levels (P <0.05). Treatment with NO reduced mortality to 0%, significantly
      decreasing TNF-alpha (P <0.001) and SOA (P <0.01) levels, ICAM-1 expression, and
      NFkappaB levels (P <0.05). CONCLUSION: The exogenous administration of NO before
      the two sequential insults controlled SIRS at biochemical level (TNF-alpha, SOA)
      and at cellular level (transcription) in a lasting manner. The cascade-like
      interrelationship of both levels and the study design do not allow us the
      pinpoint the key to its modulation.

PMID- 15734480
TI  - The role of HMGB-1 on the development of necrosis during hepatic ischemia and
      hepatic ischemia/reperfusion injury in mice.
AB  - BACKGROUND: High-mobility group 1 (HMGB-1) is a late mediator of endotoxin
      lethality in mice. The release of HMGB-1 is delayed compared to other
      proinflammatory cytokines that mediate shock and tissue injury. The purpose of
      this study was to investigate the role of HMGB-1 levels in response to hepatic
      ischemia, hepatic I/R injury, and the relationship between changes in HMGB-1 and
      other cytokines. MATERIALS AND METHODS: Three murine models were employed: our
      robust model of segmental hepatic warm ischemia (SHWI), a model of partial
      hepatic ischemia/reperfusion injury (PHIRI), and a model of total hepatic
      ischemia/reperfusion injury (THIRI). Over a 48-h period following ischemic insult
      and reperfusion using these models, serum HMGB-1 concentrations, concentrations
      of HMGB-1 in ischemic and nonischemic lobes, and serum concentrations of TNF
      alpha and IL-6 levels were determined in mice. An anti-HMGB-1 antibody treatment
      was used in SHWI and THIRI to evaluate what aspects of response to ischemia and
      reperfusion were potentially mediated by HMGB-1. RESULTS: Hepatic HMGB-1 tissue
      concentrations exhibited biphasic changes in SHWI mice, which were increased in
      the ischemic lobes relative to nonischemic lobes at 12 h but decreased relative
      to nonischemic lobes at 24 h after ischemic insult. These results suggested that
      HMGB-1 was released into the systemic circulation by necrotic cells over the
      first 12 h but this process may be complete by 24 h postischemia. By 6 to 12 h
      after SHWI, serum TNF-alpha began to increase significantly and continued to
      increase for 18 h, followed by a sudden decline. Similarly, serum IL-6 increased
      over 1-3 h after SHWI and then decreased over the next 6 h. Treatment with an
      anti-HMGB-1 antibody significantly prolonged survival time in SHWI and THIRI.
      CONCLUSIONS: HMGB-1 plays a significant role in the response to hepatic ischemia
      and hepatic ischemia/reperfusion injury. The present study demonstrated a time
      dependent production of HMGB-1 following hepatic warm ischemia in mice. The
      inherent HMGB-1 in ischemic areas was exhausted and HMGB-1 may be released by
      necrotic cells. HMGB-1 activation is involved in immediate proinflammatory stress
      response to I/R and anti-HMGB-1 antibody treatment remarkably improved survival.
      We demonstrated that systemic HMGB-1 accumulation was measured at an earlier
      phase of the hepatic ischemia and ischemia/reperfusion injury model than LPS
      induced endotoxemia.

PMID- 15734481
TI  - The effects of selective nitric oxide synthase blocker on survival, mesenteric
      blood flow and multiple organ failure induced by zymosan.
AB  - BACKGROUND: Circulatory failure in multiple organ dysfunction syndromes (MODS) is
      characterized with systemic vasodilation, diminished blood flow to various
      vascular beds. The aim of this study was to investigate the effects of selective
      inhibition of nitric oxide on the mesenteric arterial blood flow (MABF), survival
      and organ injury of the liver, kidney, lung and spleen in zymosan-induced MODS.
      MATERIALS AND METHODS: Forty Swiss albino mice (20-40 g), 7 to 9 weeks old, were
      obtained. Animals were randomly divided into four groups. The first group were
      treated intraperitoneally (i.p) with vehicle (saline) and served as a sham group
      for aminoguanidine (AG) (n=10). The second group was treated with zymosan (500
      mg/kg, suspended in saline solution, i.p). The mice in the third and fourth group
      received AG (15 mg/kg) 1 h and 6 h after zymosan or saline administration,
      respectively. Eighteen hours after the administration of zymosan, animals were
      assessed for MODS described subsequently. The signals from the flowmeter were
      also recorded on mesenteric arterial blood flow values. RESULTS: In zymosan
      treated animals, the MABF was significantly lower than that of solvent (saline)
      treated controls (ml min(-1), controls: 4.6 +/- 0.6; zymosan: 1.6 +/- 0.9, P
      <0.05). When animals were treated with AG, there were no significant differences
      in MABF values between AG group and solvent (saline)-treated control group.
      However AG prevented zymosan-induced mesenteric MABF decrease. Treatment with
      aminoguanidine also decreased mortality. CONCLUSION: AG is capable of inhibiting
      both the induction and the activity of the already iNOS; it remains a potential
      therapeutic agent in patients with MODS.

PMID- 15734482
TI  - K-ras mutation influences macroscopic features of gastric carcinoma.
AB  - INTRODUCTION: Gastric carcinoma is classified morphologically as type 1 to 4.
      Type 1 is defined as a polypoid tumor; types 2 and 3 are defined as ulcerated
      tumors with polypoid growth or gastric wall infiltration, respectively, and type
      4 tumors are defined as flat. This morphological classification is important
      because biological characteristics differ between the four morphological types,
      but little is known about genetic differences between them. MATERIALS AND
      METHODS: One hundred eight gastric tumors were classified macroscopically as type
      1 to 4. Tumoral DNA was microdissected from paraffin-embedded tissue sections.
      PCR amplification of exon 1 of a K-ras containing codons 12 and 13 was performed.
      K-ras amplicons were dot-blotted onto nylon filters and hybridized with
      radiolabeled oligomer primers. RESULTS: A K-ras mutation was found in 20 of 108
      gastric cancers. A significant relationship of K-ras mutation with polypoid
      cancer was found. The frequency of K-ras mutation was 6/14 (43%), 8/29 (28%),
      2/11 (18%), and 4/54 (7%) in type 1 to 4 tumors, respectively. K-ras mutation was
      correlated with well-differentiated tumors. Of various types of K-ras mutations,
      12 Asp often was seen in type 1 and 2 gastric cancers (well-demarcated, elevated
      tumors), while 12 Val and 12 Ser were often seen in type 3 and 4 cases
      (infiltrating carcinomas). CONCLUSION: K-ras mutations occur prominently in type
      1 and type 2 gastric cancers.

PMID- 15734483
TI  - Protective effect of fibronectin for endotoxin-induced liver injury after partial
      hepatectomy in rats.
AB  - BACKGROUND: Endotoxemia may occur after hepatectomy and become the cause of post
      operative death. Fibronectins (Fns) are involved in a number of biological
      processes, such as cellular adhesion, motility, differentiation, apoptosis,
      hemostasis, wound healing, and ischemic injury. Studies were performed to
      determine whether Fn influences the survival rate of rats subjected to endotoxin
      induced liver injury after partial hepatectomy. MATERIALS AND METHODS:
      Lipopolysaccharide (LPS) was administered intravenously to male Sprague-Dawley
      rats within 48 h of 70% hepatectomy. Before LPS administration, plasma Fn or
      bovine serum albumin was given intravenously. RESULTS: The survival rate of the
      Fn-treated group was markedly improved compared with that of the controls. Fn
      prevented increases in the concentrations of serum enzymes and total bilirubin
      related to liver injury. The levels of inflammatory cytokines, including tumor
      necrosis factor-alpha, interleukin-1beta, and cytokine-induced neutrophil
      chemoattractant, in serum and liver tissue, also were significantly lower in the
      Fn-treated group than in the control group. Furthermore, the degree of apoptosis
      and necrosis in remnant liver was significantly decreased in the Fn-treated rats
      compared with the controls. CONCLUSIONS: These results indicate that Fn prevents
      endotoxin-induced liver injury after partial hepatectomy, at least in part
      through the inhibition of production of inflammatory cytokines, necrosis and
      apoptosis in the remaining liver.

PMID- 15734484
TI  - Effect of vessel diameter on the creation of ovine lung radiofrequency lesions in
      vivo: preliminary results.
AB  - OBJECTIVE: We sought to evaluate the effect of radiofrequency ablation (RFA) on
      pulmonary vessels with respect to potential of injury of these structures, to
      assess perfusion-mediated "heat sink" effect, and to consider acute and chronic
      complications. MATERIAL AND METHODS: RFAs targeted to perihilar, middle third,
      and peripheral lung regions were created in vivo in the lung of 10 crossbred
      sheep. The RITA generator and the Starburst XLi electrode with deployable hooks
      were used. The approach was open, performed under general anesthesia. Lesions 4
      cm in diameter at a target temperature of 80 degrees C were created. Acute
      (immediate postinterventional euthanasia), subacute (96 h), and chronic (28 days)
      lesions were evaluated macroscopically, and histologic analysis of the vessels
      was performed. Patency of the vessels, both arteries and veins, was
      macroscopically assessed by presence or absence of thrombus and the degree of
      vascular injury and the viability of perivascular pneumocytes as well as
      endobronchial injury were histologically assessed. RESULTS: In the acute,
      subacute, and chronic setting, heat sink effect, indicated by invagination of the
      tissue between vessel and ablated region, was only observed in vessels greater
      than 3 mm in diameter. Thrombus was seen in 20% of the vessels smaller than 3 mm.
      On histopathology, vessels smaller than 3 mm showed at least partial vessel wall
      injury, characterized by endothelial cell necrosis and luminal thrombus. In the
      vessels greater than 3 mm the extent of vessel wall injury decreased with
      increasing vessel diameter. No acute complications were noted. For the chronic
      complications a bronchopleural fistula and a lung abscess were found. CONCLUSION:
      There seems to be a narrow transition zone for pulmonary vessels around 3 mm,
      beyond which the heat sink effect was seen consistently and substantial vascular
      injury was rare.

PMID- 15734486
TI  - Altered intestinal motility in leptin-deficient obese mice.
AB  - INTRODUCTION: Leptin is produced by adipocytes and causes satiety by regulating
      hypothalamic neurotransmission and energy expenditure. Leptin functions through
      the active long form of its receptor, which is expressed throughout the
      gastrointestinal tract, including the vagal neurons concerned with small
      intestinal motility. However, the role of leptin in small intestinal motility is
      poorly understood. Therefore, we hypothesized that leptin-deficient (Lepob) obese
      mice would have altered small intestinal response to neurotransmitters and
      transit time. MATERIALS AND METHODS: Responses of jejunal and ileal segments from
      lean control and leptin-deficient obese animals to acetylcholine (ACh) and
      cholecystokinin (CCK) were determined in an organ bath. In addition, gastric
      emptying was determined as the amount of gavaged liquid diet remaining in the
      stomach after 1 h, and intestinal transit time was determined by calculating the
      geometric center (GC) of passage of a fluorescent-labeled marker. RESULTS: Leptin
      deficiency resulted in increased jejunal responses to CCK (P <0.05) and a similar
      response to ACh compared to lean controls. Also, gastric emptying (97% versus
      91%, P <0.001) in obese mice was greater. Overall small intestinal transit (GC)
      in obese mice was decreased (7.3 versus 8.4, P <0.05) even though proximal
      transit was increased (5.3 versus 1.5, P <0.06). CONCLUSIONS: These studies
      indicate that leptin-deficient (Lepob) obese mice have an increased jejunal
      response to CCK as well as an increased proximal intestinal transit, but an
      overall decrease in small intestinal transit.

PMID- 15734485
TI  - No apparent association between genetic polymorphisms (-102 C>T) and (-9 T>C) in
      the human manganese superoxide dismutase gene and gastric cancer(1).
AB  - BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the
      detoxification of mitochondrial reactive oxygen species, constituting a major
      cellular defense mechanism against agents that induce oxidative stress. A genetic
      polymorphism in the mitochondrial targeting sequence of this gene has been
      associated with increased cancer risk. This one base pair transition (-9 T>C)
      leads to a Val to Ala amino acid change in the mitochondrial targeting sequence.
      In addition, the MnSOD promoter contains an activator protein-2 (AP-2) binding
      site that modifies transcription of MnSOD. Mutations have been identified in the
      proximal region of the promoter in human tumor cell lines. One of these mutations
      (-102 C>T) has been shown to change the binding pattern of AP-2, leading to a
      reduction in transcriptional activity. The aim of our study was to investigate
      possible associations of the (-9 T>C) and (-102 C>T) polymorphisms with gastric
      cancer in a population-based case-control study conducted in Warsaw, Poland.
      MATERIALS AND METHODS: DNA was obtained from a population based case-control
      study of stomach cancer conducted in Warsaw, Poland, between 1994 and 1996. The
      MnSOD -9 T>C genotype was determined by PCR-RFLP assay. The MnSOD -102 C>T
      genotype was determined using a TaqMan allele discrimination assay. RESULTS: The
      frequency of the -102 C>T polymorphism was 41% (38/91) in gastric cancer cases
      and 38% (50/130) in the controls (odds ratio [OR] 1.1, 95% confidence interval
      [CI] 0.6-2.1). The frequency of the -9 T>C polymorphism was 44% (202/464) in
      cases and 56% (262/464) in controls (OR 1.1; 95% CI 0.9-1.37). The lack of
      association was observed in both non-smokers (OR 1.5; 95% CI 0.7-2.34) and
      smokers (OR 1.1; 95% CI 0.7-1.7). Furthermore, the association was not
      significant when smokers were segregated by extent of smoking history.
      CONCLUSION: The association of the manganese superoxide dismutase polymorphisms
      at -102 C>T and the -9 T>C were not found to be associated with gastric cancer in
      a Polish case-control study.

PMID- 15734487
TI  - Effects of progesterone and estrogen on endothelial dysfunction in porcine
      coronary arteries.
AB  - BACKGROUND: The effects of hormone replacement therapy (HRT) on the vascular
      endothelium have been controversial. In this study, we determined the effects of
      HRT on endothelium-dependent relaxation in a porcine coronary artery model.
      METHODS: Coronary artery rings harvested from female swine were incubated as
      controls or with estrogen (10(-9), 10(-8), 10(-7) g/L), progesterone (1 x 10(-6),
      1 x 10(-5), 5 x 10(-5) g/L), or a combination of the two (10(-8)g/L estrogen, 1 x
      10(-5)g/L progesterone). After 24 h in tissue culture, the rings were tested on a
      myograph system to measure contraction and endothelium-dependent relaxation.
      Myograph analysis was performed with the thromboxane A2 analogue U46619 for
      contraction and bradykinin or sodium nitroprusside for relaxation. Nitric oxide
      synthase (eNOS) levels were determined by immunohistochemistry. Levels of
      superoxide anion in the progesterone or estrogen treated tissues were assessed by
      lucigenin-enhanced chemiluminescence analysis. RESULTS: In response to 10(-7)M
      bradykinin, porcine coronary artery rings treated with 1 x 10(-6), 1 x 10(-5) and
      5 x 10(-5) g/L of progesterone showed a significant reduction in endothelium
      dependent vasorelaxation by 36%, 45%, and 68%, respectively, as compared to
      controls (P <0.05). However, rings treated with estrogen showed no significant
      difference as compared to controls. Furthermore, estrogen treatment with
      progesterone reversed the effect of progesterone, showing no difference in vessel
      relaxation as compared to controls. There were no differences in endothelium
      independent vasorelaxation (sodium nitroprusside) or in smooth muscle
      contractility (U46619) between the control and the hormone-treated groups. The
      eNOS immunoreactivity was reduced in progesterone-treated coronary artery rings.
      Furthermore, coronary endothelium exposed to progesterone showed a 59% increase
      in superoxide anion production, while estrogen produced a 67% decrease when
      compared to controls (P <0.05 for both). CONCLUSION: This data suggests that the
      progesterone component of HRT has a detrimental influence on endothelium
      dependent relaxation. This effect appears to be related to decreased eNOS levels,
      as well as increased consumption of NO by superoxide anion in the endothelium of
      tissues exposed to progesterone. Estrogen can block progesterone-induced
      endothelial dysfunction and superoxide anion production in the pig coronary
      artery model.

PMID- 15734488
TI  - Pressure-induced cellular senescence: a mechanism linking venous hypertension to
      venous ulcers.
AB  - INTRODUCTION: Slow healing of ulcers in chronic venous insufficiency (CVI) has
      long been thought secondary to venous hypertension. Dermal fibroblasts isolated
      from venous ulcers have morphologies and protein production suggestive of
      premature aging. In this study, we hypothesized that neonatal fibroblasts (NNF)
      cultured under elevated pressure will demonstrate premature aging and that this
      effect will be augmented by an inflammatory mediator, transforming growth factor
      beta (TGF-beta). MATERIALS AND METHODS: A unique pressure incubator was used to
      culture NNF at atmospheric pressure (ATM), ATM + 30 mmHg, ATM + 60 mmHg, and ATM
      +120 mmHg. Some pressure-exposed NNF were also cultured with TGF- beta (1 ng/ml).
      Growth rates were determined by flow cytometry. Senescent cells were identified
      by staining with a marker for cellular senescence, beta-galactosidase (SA-beta
      Gal). Light microscopy and digital imaging were used to evaluate cell morphology.
      Paired linear models and comparison of the slopes were used for statistical
      analysis of growth. chi2 analysis was used to compare senescence rates. RESULTS:
      NNF cultured at ATM + 60 mmHg and ATM + 120 mmHg showed increased SA-beta-Gal
      activity (P <0.05), and reduced growth rates (P <0.05) at 11 days. These effects
      were not seen at ATM + 30 mmHg. NNF grown with TGF-beta did not show augmented SA
      beta-Gal staining. CONCLUSIONS: Pressure-exposed NNF demonstrated an accelerated
      aging phenomenon similar to fibroblasts isolated from venous ulcers. This aging
      effect was directly related to the level of pressure. TGF-beta did not augment
      the aging effect. This study suggests that pressure elevations result in altered
      cell function and accelerated aging that may contribute to the slowed healing
      seen in patients with venous insufficiency.

PMID- 15734489
TI  - Anisotropy of human linea alba: a biomechanical study.
AB  - BACKGROUND: Recently, a new model of fiber architecture of the linea alba has
      been described consisting of an oblique fiber layer of intermingling oblique
      fibers, a transverse fiber layer containing mainly transverse fibril bundles, and
      a variable, small irregular fiber layer. In this study the morphological model
      was proven using direction-specific biomechanical measurements of the linea alba.
      MATERIAL AND METHODS: Thirty-one human abdominal walls were analyzed (16 male and
      15 female). Six strips of collagen tissue with a width of 1 cm were exsected from
      each linea alba transversely, obliquely, and longitudinally according to the main
      fiber directions. An increasing force from 2 to 24 N was applied to these strips,
      and the corresponding strain represented by the relative elongation was measured,
      which allows the calculation of a direction-specific compliance of the tissue.
      RESULTS: The compliance is highest in longitudinal and smallest in transverse
      direction. In the infraumbilical part of the female linea alba the compliance was
      significantly smaller in the transverse direction than in the oblique direction.
      Moreover, the compliance in the transverse direction was significantly smaller in
      women than in men. CONCLUSIONS: A distinct anisotropy of morphological and
      biomechanical properties was demonstrated as well as sex-dependent differences.
      The compliance correlates with the distribution of fiber orientation in the linea
      alba. These biomechanical results constitute the functional correlation with the
      fiber morphology of the linea alba and correspond well to our earlier proposed
      model of fiber architecture.

PMID- 15734490
TI  - Kupffer cell ablation attenuates cyclooxygenase-2 expression after trauma and
      sepsis.
AB  - BACKGROUND: Prostaglandins, synthesized by cyclooxygenase (COX), play an
      important role in the pathophysiology of inflammation. Severe injuries result in
      immunosuppression, mediated, in part, by maladaptive changes in macrophages.
      Herein, we assessed Kupffer cell-mediated cyclooxygenase-2 (COX-2) expression on
      liver function and damage after trauma and sepsis. MATERIALS AND METHODS: To
      ablate Kupffer cells, Sprague Dawley rats were treated with gadolinium chloride
      (GdCl3) 48 and 24 h before experimentation. Animals then underwent femur fracture
      (FFx) followed 48 h later by cecal ligation and puncture (CLP). Controls received
      sham operations. After 24 h, liver samples were obtained, and mRNA and protein
      expression were determined by PCR, Western blot, and immunohistochemistry.
      Indocyanine-Green (ICG) clearance and plasma alanine aminotransferase (ALT)
      levels were determined to assess liver function and damage, respectively. One-way
      analysis of variance (ANOVA) with Student-Newman-Keuls test was used to assess
      statistical significance. RESULTS: After CLP alone, FFx+CLP, and GdCl3+FFx+CLP,
      clearance of ICG decreased. Plasma ALT levels increased in parallel with severity
      of injury. Kupffer cell depletion attenuated the increased ALT levels after
      FFx+CLP. Femur fracture alone did not alter COX-2 protein compared with sham. By
      contrast, COX-2 protein increased after CLP and was potentiated by sequential
      stress. Again, Kupffer cell depletion abrogated the increase in COX-2 after
      sequential stress. Immunohistochemical data confirmed COX-2 positive cells to be
      Kupffer cells. CONCLUSIONS: In this study, sequential stress increased hepatic
      COX-2 protein. Depletion of Kupffer cells reduced COX-2 and attenuated
      hepatocellular injuries. Our data suggest that Kupffer cell-dependent pathways
      may contribute to the inflammatory response leading to increased mortality after
      sequential stress.

PMID- 15734491
TI  - Enhancement of dorsal random-pattern skin flap survival in rats with topical
      lidocaine and prilocaine (EMLA): enhancement of flap survival by EMLA.
AB  - BACKGROUND: Various topical pharmacologic agents have been investigated for their
      efficacy in preventing or reversing skin flap ischemia. Most of these studies
      have focused on agents that act on the vascular smooth muscles to cause
      vasodilatation and improve circulation in the flap. Most of local anesthetics
      relax vascular smooth muscle and produce peripheral vasodilatation. Topical
      lidocaine administration was shown that it was an effective and prompt resolution
      of mechanically induced vasospasm. The topical analgesia cream, EMLA is a mixture
      of the substances lidocaine and prilocaine. EMLA causes a biphasic vascular
      response comprising initial blanching and vasoconstriction (maximal after 1.5 h
      of application) and late erythema and vasodilatation at application times longer
      than 3 h. MATERIALS AND METHODS: To investigate the effect of EMLA on random flap
      survival, 40 rats were divided in 2 groups of 20 animals. Caudally based random
      pattern skin flaps were elevated on dorsa of the rats in 10 x 3 cm dimensions. In
      group 1 which was the treatment group, topical EMLA was applied and covered with
      Opsite for 1 week whereas in group 2 which was the control group, carrier for
      EMLA was applied to the flaps. At the end of treatment period, the areas of flap
      necrosis were measured and percentages of flap survivals were calculated.
      RESULTS: The mean percentages of flap survivals in group 1 and 2 were 81.2 +/-
      1.2 percent and 58.7 +/- 2.3 percent, respectively. CONCLUSION: Topically
      administered EMLA might lead to a significant improvement in flap survival. In
      addition, it is safe, cost-effective, easily applied, and clinically available.

PMID- 15734492
TI  - Effects of TVE application during 70% hepatectomy on regeneration capacity of
      rats.
AB  - BACKGROUND: For adequate control of excess bleeding during liver resection, total
      vascular exclusion (TVE) is preferred by surgeons, especially when the tumor is
      located in the posterior liver lobes or near the cava. To the authors' knowledge,
      the effects of TVE technique on the postoperative liver regeneration process have
      not thus far been evaluated yet in the literature. This study was planned to
      compare the effects of liver resections performed either with portal pedicle
      clamping or with TVE on the regeneration process. MATERIALS AND METHODS: Seventy
      percent hepatectomy was performed with portal pedicle clamping (n=10, Group A) or
      with TVE (n=10, Group B) in rats. At 48 h after resection, sampling was performed
      for the measurement of serum transaminase, alkaline phosphatase (ALP), tissue
      malondialdehyde (MDA), and glutathione (GSH) levels. Liver regeneration rate,
      proliferating cell nuclear antigen (PCNA) labeling, and mitotic indices were also
      evaluated. RESULTS: Liver injury determinants (serum transaminases, ALP, and
      tissue MDA levels) were found significantly higher in group B than in group A.
      Liver regeneration rate, liver GSH levels, PCNA labeling index, and mitotic index
      were significantly lower in group B than in group A. CONCLUSIONS: The injury
      during TVE seems to be greater than during resection with portal pedicle
      clamping. The negative effect of this oxidative damage may influence the
      regenerative capacity of the remnant liver tissue.

PMID- 15734493
TI  - Leptin increases small intestinal response to cholecystokinin in leptin-deficient
      obese mice.
AB  - INTRODUCTION: Leptin receptors are present in the jejunum, ileum, and vagal
      neurons. Leptin increases duodenal secretion of cholecystokinin (CCK) and acts
      with CCK on vagal mechanoreceptors in the regulation of small intestinal
      motility. We have demonstrated that leptin-deficient (Lepob) obese mice have
      increased jejunal and normal ileal responses to CCK. Therefore, we hypothesized
      that leptin administration alters small intestinal motility observed in leptin
      deficient obese mice. MATERIALS AND METHODS: Twelve-week-old female leptin
      deficient (Lepob) obese mice received either saline (n=12) or 5 microg/g leptin
      ip (n=12) injections daily. After 4 weeks, jejunal and ileal segments were
      harvested, mounted in an organ bath, and reacted with acetylcholine (ACh, 10(
      5)M) and CCK (10(-8,-7,-6)M). Data were expressed as N/cm2 and compared by ANOVA
      and Student's t test. RESULTS: The average body weights in the leptin-treated
      group were significantly decreased compared to those of the saline-treated group
      (34 versus 49 g, P <0.01). Jejunal responses to ACh within each group were
      significantly decreased (P <0.05) when compared to ileal responses. No
      significant differences in responses to ACh were observed between groups. Jejunal
      responses to 10(-7,-6)M CCK in the leptin-treated group were significantly
      greater than those in the saline-treated group. Ileal responses in the leptin
      group were similarly increased at all CCK concentrations. CONCLUSIONS: These data
      suggest that daily leptin administration for 4 weeks in leptin-deficient (Lepob)
      obese mice increases jejunal and ileal responses to CCK and does not alter
      responses to ACh. Therefore, we conclude that regulation of small intestinal
      motility may be influenced by synergistic action of cholecystokinin and leptin.

PMID- 15734494
TI  - Distribution of CD4+CD25high regulatory T-cells in tumor-draining lymph nodes in
      patients with gastric cancer.
AB  - BACKGROUND: Regulatory T-cells (T-regs) can inhibit the immune response mediated
      by T-cells. There is an increasing evidence that there is an increased proportion
      of T-regs in PBLs and tumor-infiltrating lymphocytes in several different human
      malignancies, although the mechanism remains unclear. In the present study, we
      evaluated the prevalence of CD4+CD25high T-regs in tumor-draining lymph nodes in
      patients with gastric cancers. MATERIALS AND METHODS: Regional lymph nodes in the
      stomach of the patients with gastric cancer (n=44) were classified into N1
      regional lymph nodes adjacent to the gastric tumor and N2 regional lymph nodes
      marginally distant from the tumor. The population of CD4+CD25high T-cells as a
      percentage of total CD4+ cells was evaluated by flow cytometric analysis with
      triple-color staining. Cytokine production (IL-10 and IFN-gamma) was evaluated by
      intracellular cytokine staining and the antiproliferative function of CD4+CD25+
      cells positively selected by magnetic beads was measured by evaluating the
      proliferative activity of CD4+CD25- cells in response to anti-CD3 plus anti-CD28
      in the presence of autologous CD4+CD25+ cells. RESULTS: The percentage of
      CD4+CD25high T-cells in N1 regional lymph nodes (3.1 +/- 0.3%) was significantly
      higher than that of control mesenteric lymph nodes (1.2 +/- 0.3%, P <0.01).
      Furthermore, a more extended area (N2) of regional lymph nodes, as well as
      adjacent lymph nodes (N1) to the tumors, was involved in an increased prevalence
      of CD4+CD25high T-cells according to the disease progression. The functional
      evaluations confirmed that CD4+CD25high T-cells derived from the lymph nodes have
      an inhibitory activity corresponding to T-regs. CONCLUSIONS: The populations of
      CD4+CD25high T-cells in the regional lymph nodes in patients with gastric cancer
      were significantly higher in comparison to those in control lymph nodes. The
      increased prevalence of T-regs may be one of the explanations for impaired cell
      mediated immunity in cancer-bearing hosts.

PMID- 15734497
TI  - Ventriculoperitoneal shunt of continuous flow vs valvular shunt for treatment of
      hydrocephalus in adults.
AB  - BACKGROUND: Shunting for hydrocephalus is the neurosurgical procedure most
      frequently associated with long-term complications. We developed an alternative
      to valvular shunts based on a simple shunt procedure whose functioning depends on
      a peritoneal catheter with a highly precise cross-sectional internal diameter of
      0.51 mm. Preliminary studies have shown that the shunt of continuous flow (SCF)
      is superior to valvular shunts for the treatment of hydrocephalus in adults.
      Here, we show the long-term performance of the SCF in adult patients with
      hydrocephalus secondary to a comprehensive variety of neurological disorders.
      METHODS: In a 5-year period, ventriculoperitoneal shunting was performed on 307
      patients with hydrocephalus; 114 of them were treated with the SCF and 193
      controls were treated with a conventional valvular shunt. Patients were followed
      from 1 to 5 years after surgery; endpoint observation was considered at surgical
      reintervention because of shunt failure. RESULTS: At the end of the observation
      period (44 +/- 17 months), the failure rate of the shunting device was 14% for
      the SCF and 46% for controls (P < .0002). Shunt endurance was 88% in patients
      with SCF and 60% in controls. Along the study, signs of overdrainage developed in
      40% of patients treated with valvular shunt, but they were not observed in
      patients with SCF. CONCLUSIONS: The design of the SCF was calculated according to
      the mean rates of cerebrospinal fluid production; it takes simultaneous advantage
      of the intraventricular pressure and the siphon effect and complies with the
      principle of uninterrupted flow, maintaining a fair equilibrium that prevents
      under- and overdrainage. The SCF is a simple, inexpensive, and effective
      treatment for hydrocephalus in adults.

PMID- 15734500
TI  - Diagnosis and prognostication of adult spinal cord injury without radiographic
      abnormality using magnetic resonance imaging: analysis of 40 patients.
AB  - BACKGROUND: Spinal cord injury without radiographic abnormality (SCIWORA) is not
      uncommon among middle-aged and elderly people. It is less reported in adults as
      compared with children. This study was undertaken to find the incidence, magnetic
      resonance imaging (MRI) changes, and outcome of SCIWORA in adults and to
      demonstrate the prognostic value of MRI in SCIWORA. MATERIALS AND METHODS: Forty
      adult patients who sustained SCIWORA for a period of 2 years (January 1999 to
      December 2000) were admitted to our hospital. Methylprednisolone was given in
      therapeutic doses, for a period of 24 hours, to those arriving within 6 hours of
      injury. Magnetic resonance imaging was performed within 72 hours of admission to
      the hospital. In all patients, sagittal, axial, and coronal T1, spin, and T2
      images of MRI were obtained. Clinical status of the patient at the time of
      admission and discharge was correlated with MRI. RESULTS: Four patients (10%),
      who were in Frankel grade D, with no demonstrable injury on MRI, improved to
      Frankel grade E at the time of discharge. Two patients (5%) with cord edema and
      extraneural injury improved to a useful neurological grade (Frankel grades D or
      E), whereas 13 patients (32.5%) with MRI features of cord contusion and
      hemorrhage did not achieve useful neurological function. CONCLUSION: Spinal cord
      injury without radiographic abnormality contributes 12% of cases of spinal cord
      injury. Magnetic resonance imaging is the investigation of choice, having
      diagnostic and prognostic value because it demonstrates neural and extraneural
      injuries and helps to pick up surgically correctable abnormality. Patients with
      minimal cord changes on MRI have the best outcome followed by those with cord
      edema. Patients with parenchymatous hemorrhage and contusion on MRI fare badly.

PMID- 15734502
TI  - Minimally invasive anterior contralateral approach for the treatment of cervical
      disc herniation.
AB  - BACKGROUND: During the practice of ipsilateral approach to the offending lesion
      in anterior simple discectomy, the authors realized that it achieves better
      surgical exposure of the opposite foraminal area. In addition, it was also
      realized that routine procedures for better visualization of the foraminal area,
      such as stripping longus colli muscles, further excising of the anterior
      longitudinal ligament, or using a spreader, which cause more invasive surgery
      during the standard anterior approach, are not necessary because the
      contralateral approach already achieves sufficient exposure of the target
      foraminal area. OBJECTIVE: Evaluation of the results and effectiveness of this
      minimal invasive technique in patients with either soft or hard disc herniations.
      METHODS: Between January 1994 and April 2002, 216 patients underwent anterior
      contralateral microdiscectomy without fusion for cervical disc herniation at 1 or
      2 adjacent levels. Anterior contralateral microdiscectomy is a less invasive
      technique than standard anterior simple discectomy in which longus colli muscles
      are not stripped, and the lateral part of annulus fibrosis at the side of
      intervention and ventrolateral part of it at the opposite side are not removed.
      In addition, a mini Zenker handheld retractor is used for retraction of
      paravertebral soft tissues and a spreader is not used during the discectomy
      procedure. There were 182 patients diagnosed with radiculopathy and 34 patients
      with myelopathy. Assessments of the neurological status of patients with
      radiculopathy were done by physical examinations, and of those with myelopathy
      according to the modified Japanese Orthopaedic Association cervical spine
      functional assessment scale. These neurological assessments were repeated in the
      18th month after surgery. In the follow-up period, the outcomes of surgery were
      also assessed for all patients in 4 categories, from failure to excellent.
      RESULTS: Surgery outcomes generally have been good to excellent and none of the
      patients were made worse by the procedure. The outcomes were significantly better
      in the radiculopathy and soft disc herniation groups. Other positive outcome
      factors were short duration and sudden onset of symptoms, normal cervical
      curvature, and single-level disease. Follow-up radiological studies revealed
      fibrous healing with normal or slight loss of disc height in 199 (92.1%) patients
      and total obliteration of the involved disc space representing radiological
      fusion signs in 13 (6%) patients. The overall complications observed in this
      study were 2 spontaneous and 2 postinfection collapses of disc level, 1 excessive
      fibrosis of disc level, and 2 adjacent-level diseases. CONCLUSION: Anterior
      contralateral microdiscectomy without fusion achieves better exposure for
      resection of the offending foraminal or far lateral lesions, ventral osteophytes,
      or a disc fragment under direct microscopic visualization. Collapse and
      instability of the involved disc level can also be avoided via this less invasive
      technique.

PMID- 15734505
TI  - Acute arm paresis with cervical spondylosis: three case reports.
AB  - BACKGROUND: The mild type of anterior spinal artery syndrome (ASAS) is
      characterized by motor loss with an absent or insignificant sensory deficit due
      to a disturbance in the blood supply to the anterior horn of the spinal cord. The
      clinical symptoms of cervical spondylotic amyotrophy (CSA) are motor loss or
      atrophy with an absent or insignificant sensory deficit or a long tract sign;
      however, the pathophysiology has not been clarified. METHODS: Three patients who
      suffered from palsy of the deltoid and biceps brachii are presented. Magnetic
      resonance imaging confirmed the intrinsic cord disease as the cause of the
      paresis. We measured the central motor conduction time (CMCT) and the latencies
      of the tendon reflex (T waves) of the biceps and triceps and those of the F waves
      of the abductor pollicis brevis and abductor digiti minimi before, 2 weeks after,
      and 3 months after starting intravenous injections of prostaglandin E(1)
      (PGE(1)). RESULTS: In these 3 cases, restoration of muscle strength began after
      starting injection of PGE(1). The electrophysiologic diagnosis revealed a
      disturbance of the motor conduction, in the CMCT and the latencies of the T
      waves, in the paretic muscle, which is more severe than that in other muscles.
      The radiological diagnosis suggested damage in the spinal cord. Improvements in
      the disturbance of the motor conduction and those of symptoms were parallel.
      CONCLUSION: From symptomatologic or radiological viewpoints, it is difficult to
      differentiate CSA from ASAS with cervical spondylosis. This suggests that there
      have been patients with ASAS whom we have diagnosed as CSA, and we may add
      administration of PGE(1) to the treatment for the patients with CSA. The present
      3 patients showed improvement of muscle strength after starting injections of
      PGE(1). Although this improvement was measured by an electrophysiologic method,
      the mechanisms of PGE(1) require further study.

PMID- 15734507
TI  - Subarachnoid hemorrhage on computed tomography scanning and the development of
      cerebral vasospasm: the Fisher grade revisited.
AB  - BACKGROUND: The Fisher grade (FG) is widely used to predict cerebral vasospasm
      after aneurysmal subarachnoid hemorrhage (SAH). We revisited the grading scale to
      determine its validity in the era of modern management. METHODS: We
      retrospectively reviewed the records of 134 patients with SAH. The amount and
      distribution of subarachnoid blood on admission computed tomography (CT) scan was
      quantified according to the FG and compared with development of symptomatic
      vasospasm. RESULTS: We reviewed 134 patients (median age, 54) who presented with
      aneurysmal SAH. Six (5%) were FG 1, 34 (25%) were FG 2, 25 (19%) were FG 3, and
      69 (51%) were FG 4. Symptomatic vasospasm developed in no (0%) FG 1, 8 (24%) FG
      2, 7 (28 %) FG 3, and 13 (19%) FG 4 patients (28 of 134 total patients; 21%).
      Development of symptomatic vasospasm was not associated with admission FG, Hunt
      and Hess grade, age, sex, or location of blood on presenting CT scan. Elevated
      transcranial Doppler blood flow velocity was associated with blood in the basal
      cisterns (P = .0047), lateral ventricles (P = .026), or blood in any ventricle (P
      = .04). Postoperative angiograms were obtained in 57 patients; moderate to severe
      vasospasm was observed in 5 (15%) FG 2, 6 (24%) FG 3, and 14 (20%) FG 4 patients.
      Twenty patients (71%) with symptomatic vasospasm had moderate or severe
      angiographic vasospasm. Angiographic vasospasm was associated with
      intraventricular blood (P = .054) but not with FG. CONCLUSIONS: Symptomatic
      vasospasm occurred in 21% of cases. The FG correlated with symptomatic vasospasm
      in only half the patients. A new predictive CT grading scale for vasospasm may be
      necessary.

PMID- 15734510
TI  - Late morphological progression of a dissecting basilar artery aneurysm after
      staged bilateral vertebral artery occlusion: case report.
AB  - BACKGROUND: The authors present a patient who experienced late (5-year follow-up)
      morphological progression of a dissecting aneurysm of the distal basilar artery
      after treatment with a combined microsurgical and neuroendovascular Hunterian
      strategy. In addition to postulating about the possible reasons underlying the
      evolution of this lesion, the role of stenting is discussed. CASE DESCRIPTION:
      The patient was 37 years old when she suffered a subarachnoid hemorrhage from
      spontaneous basilar artery dissection. At the time of the hemorrhage, minimal
      aneurysmal enlargement was noted angiographically, and she was therefore treated
      nonoperatively. On reimaging 5 months later, massive enlargement of the aneurysm
      was noted. The patient was treated with staged bilateral vertebral artery
      sacrifice using a combination of microsurgical and neuroendovascular techniques.
      The dominant vertebral artery was clip-ligated distal to the posteroinferior
      cerebellar artery, whereas the contralateral vertebral artery was coil-occluded
      cervically 1 week later. CONCLUSIONS: Despite the patient remaining asymptomatic,
      follow-up angiography 5 years after the initial hemorrhage revealed further
      enlargement of the aneurysm as well as a newly discovered inferiorly projecting
      daughter sac measuring 5 mm in diameter. Clearly, certain aneurysms exist for
      which indirect approaches involving hemodynamic attenuation fail to prevent
      progression. With greater refinements in stent technology, such lesions may be
      more effectively treated.

PMID- 15734513
TI  - Ruptured saccular aneurysm of distal vertebral artery fenestration managed with
      Guglielmi detachable coils and intraventricular tissue plasminogen activator.
AB  - BACKGROUND: Aneurysms associated with vertebrobasilar fenestrations are uncommon.
      We report on an unusual presentation of such aneurysm with a dedicated arterial
      pedicle, manifesting with significant intraventricular hemorrhage. Equally
      important, the aneurysm was managed in a multidisciplinary fashion, which, we
      think, greatly contributed to a good outcome. CASE DESCRIPTION: A 55-year-old man
      presented in good condition after subarachnoid and massive intraventricular
      hemorrhage. The aneurysm location and the extent of intraventricular hemorrhage
      both presented concerns regarding treatment approach. The aneurysm was first
      treated with transarterial coil obliteration, and intraventricular tissue
      plasminogen activator (tPA) infusion was given, with rapid resolution of evolving
      hydrocephalus. The patient had an excellent outcome. CONCLUSION: To our
      knowledge, this is the first report of a vertebrobasilar fenestration saccular
      aneurysm with a dedicated pedicle projecting toward the foramen of Magendie with
      significant intraventricular hemorrhage. In addition, this patient was
      successfully managed with endovascular obliteration and intraventricular tPA
      infusion.

PMID- 15734516
TI  - Correspondence of microelectrode mapping with magnetic resonance imaging for
      subthalamic nucleus procedures.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) and microelectrode recording (MER)
      are commonly used to guide stereotactic procedures on the subthalamic nucleus
      (STN). Little is known about the correlation between the position of the STN as
      seen on MRI and that as determined by MER mapping. We compared these in 10
      patients with Parkinson's disease. METHODS: The position of the STN was
      determined by intraoperative MER findings and stereotactic axial T2 magnetic
      resonance images with 2-mm slice thickness. Images were reconstructed in a 3
      dimensional workstation. The anterior, posterior, medial, lateral, dorsal, and
      ventral borders of the STN defined with the MRI were measured relative to the
      midcommissural point. The location of STN activity during MER was reconstructed
      relative to the midcommissural point for comparison. RESULTS: Twenty-nine tracks
      recorded with microelectrodes provided clear spans of STN-like activity in 18 STN
      nuclei. The coordinates of MER were, in general, within the borders of the STN
      defined with the MRI. However, when analyzed individually, some of the tracks had
      STN-like activity outside the borders of the MRI-defined nucleus (mostly <1 mm).
      Three tracks had STN-like activity recorded between 2 and 3 mm more anterior than
      the anterior border of the nucleus defined with the MRI. CONCLUSIONS: There was a
      good correlation between MER and the borders of the STN defined in the MRI,
      except for the anterior-posterior axis, in which MER indicated that the STN
      extended more anteriorly than as suggested by MRI. This should be taken into
      account in STN surgery.

PMID- 15734518
TI  - Intracranial fungal granuloma: analysis of 40 patients and review of the
      literature.
AB  - OBJECTIVE: To describe the characteristics of patients diagnosed with
      intracranial fungal granuloma (IFG) in the largest reported series to date (to
      our knowledge). METHODS: A 22-year retrospective, multi-institutional review of
      40 patients, aged 16 to 62 years (mean, 40.2 years), was performed in patients
      with histopathologically confirmed IFG. The variables were symptoms/signs at
      presentation, predisposing factors, location of granuloma, involvement of
      paranasal sinuses, diagnostic studies including blood and urine cultures,
      surgical procedures performed, specific organism identified, treatment, and
      prognosis. Plain x-rays, computed tomography, and/or magnetic resonance imaging
      scans were performed. RESULTS: Predominant symptoms included headache (83%),
      vomiting (65%), proptosis (48%), and visual disturbances (48%). Other symptoms
      were fever, nasal congestion, and seizures (7 [18%]). Common signs included
      papilledema (12 [30%]), with cranial neuropathy (I, III/IV/VI, and V in 4, 7, and
      2 patients, respectively), hemiparesis (3), and meningismus (3). Predisposing
      factors were diabetes (16 [40%]), tuberculosis (7 [18%]), and immunocompromise
      related to renal transplant (2), non-Hodgkin's lymphoma (1), and human
      immunodeficiency virus (1). Location was primarily frontal (10 [25%]), with
      anterior cranial fossa involved in 8 (20%) patients; 6 (15%) patients had
      sellar/parasellar involvement. Eighteen (40%) had paranasal sinus involvement.
      Twenty-nine patients underwent craniotomy for resection, with 11 undergoing
      biopsy (of which 3 were transsphenoidally approached). Histopathology revealed
      aspergilloma (25 [63%]), mucormycosis (7 [18%]), cryptococcoma (3),
      cladosporidium (3), Bipolaris hawaiiensis (1), and Candida species(1).
      Microbiological analysis of the specimen was positive in 28 (60%) patients. All
      patients were treated with amphotericin B, fluconazole, and/or flucytosine. Only
      26 patients completed amphotericin B therapy (due to nephrotoxicity). Mortality
      was 63%, most commonly due to meningoencephalitis (16 [36%]). CONCLUSIONS: High
      index of suspicion of IFG should exist for the following groups: (1)
      immunocompromised patients with intracranial lesions and (2) diabetic patients
      with intracranial and rhinocerebral mass lesions. Early diagnosis, surgical
      decompression, and a complete course of promptly initiated antifungal therapy are
      associated with better prognosis.

PMID- 15734520
TI  - Long-term survival in a child with a brain stem dermoid cyst.
AB  - BACKGROUND: Brain stem dermoid cysts are very rare lesions, and in most, the
      outcome has been very poor. Because of the dangers of dissecting the cyst wall
      away from the brain stem parenchyma, some authors have advocated not to attempt a
      radical resection. METHODS: We describe a child in whom the brain stem dermoid
      cyst recurred rapidly after a conservative approach. We therefore attempted a
      radical removal. RESULTS: During surgery, the almost complete resection of the
      cyst wall was not very difficult, leading to an apparent cure after 4 years.
      CONCLUSION: In exceptional cases, it may be possible to remove a brain stem
      dermoid cyst without prohibitive morbidity and with long-term cure.

PMID- 15734522
TI  - Surgical treatment of temporal bone chondroblastoma.
AB  - BACKGROUND: Temporal bone chondroblastoma is a rare primary bone tumor that
      affects the floor of the middle cranial fossa. This tumor is known to have high
      recurrence rate after curettage, and wide resection is therefore recommended.
      However, the literature provides little information regarding long-term results
      after wide resection of temporal bone chondroblastoma. METHODS: Four cases of
      surgically treated temporal bone chondroblastoma underwent long-term follow-up.
      RESULTS: Four patients, 3 males and 1 female, with mean age of 34, were
      surgically treated at the neurosurgery department of Keio University Hospital.
      Two patients were treated for recurrent tumor and the other two for new disease.
      In all cases the tumor mainly involved the mandibular fossa with variable degree
      of infiltration into tympanic and petrous parts. The tumor was totally removed
      via zygomatic approach in all patients. In 3 patients, the mandibular condyle was
      removed to expose the tumor. These patients had temporary malocclusion and
      restricted motion postoperatively, which resolved within 3 to 12 months with
      conservative treatment. All patients have no recurrence to date with a mean
      follow-up period of 9 years. CONCLUSION: Temporal bone chondroblastoma was
      removed totally with skull base surgical technique and no recurrence has occurred
      for 6 to 13 years postoperatively. We found that removal of the mandibular head
      does not cause permanent problems of mastication in patients with normal
      dentures.

PMID- 15734524
TI  - Meningeal melanocytoma of the posterior fossa: case report and literature review.
AB  - BACKGROUND: Meningeal melanocytomas are rare primary melanotic tumors of the
      leptomeninges. According to our review of the literature, just 22 cases of
      meningeal melanocytoma (MM) of the posterior fossa have been previously reported.
      Some aspects related to diagnosis, radiological appearance, histopathologic
      features, and management are discussed in this paper. CASE DESCRIPTION: We
      describe the case of a 42-year-old female presenting with severe headache,
      nausea, and vomiting. Computed tomography and magnetic resonance imaging
      demonstrated a posterior fossa lesion that was surgically treated.
      Histopathologic examination showed a highly cellular melanocytic neoplasm with
      numerous dark pigments in the cytoplasm. Immunoperoxidase staining S-100 protein
      and HMB 45 demonstrated immunoreactivity for both, confirming the diagnosis of
      MM. CONCLUSIONS: In conclusion, MMs are rare histologically benign tumors that
      can be cured by complete surgical resection alone, which should be the goal of
      the treatment. These lesions, although rare, should be considered in the
      differential diagnosis of tumors of the posterior fossa.

PMID- 15734527
TI  - Melanotic neuroectodermal tumor of infancy in the skull: case report and review
      of the literature.
AB  - BACKGROUND: Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm
      that develops during the first year of life and grows rapidly. Early diagnosis
      and radical surgery are critical for a long-term cure. We report a rare case of
      MNTI in the skull and discuss the importance of the radical surgery and the long
      term follow-up results. CASE PRESENTATION: We describe a case of a 4-month-old
      girl with an MNTI in the skull who underwent the operation 11 years ago. The mass
      in the frontotemporosphenoid region grew rapidly after birth. The patient
      underwent a craniotomy. By referring to the histological findings of frozen
      section during surgery, a total excision of the tumor including its adjacent
      hypertrophic bone was performed. The patient has remained well without evidence
      of recurrence or neurological abnormality for 11 years. CONCLUSION: Radical
      surgery for MNTI provides complete cure. According to the literature including
      our case, there should be follow-up for at least 2 years after surgery.
      Especially in cases in which tumors recur, follow-up should be for longer periods
      because of the possibility of its malignant change.

PMID- 15734529
TI  - Intraspinal clear-cell meningioma: case report and review of literature.
AB  - BACKGROUND: Intraspinal clear-cell meningioma (CCM) is a rare morphological
      variant of meningioma with only 16 documented cases. We report one case and
      review the literature regarding intraspinal CCM. CASE PRESENTATION: A 2-year-old
      boy and a 2-month-old male infant presented with knee pain and leg weakness.
      Magnetic resonance imaging revealed an intradural extramedullary neoplasm at T10
      L1. The patient underwent radical resection of the tumor. Pathology and
      immunohistochemical study demonstrated a CCM. Unfortunately, the patient had a
      recurrence 5 years after the operation. CONCLUSION: Intraspinal CCMs are very
      uncommon tumors. They usually show aggressive behavior with local recurrence
      observed in slightly more than half of all patients. We recommend serial imaging
      studies every 3 to 6 months during the first several years, after which an annual
      imaging study should be performed for follow-up.

PMID- 15734532
TI  - The kings and queens of medicine have died.

PMID- 15734528
TI  - Giant cranial extradural primary fibroxanthoma: a case report.
AB  - Primary fibroxanthoma of the cranium is an extremely rare condition. Xanthomatous
      tumors of the central nervous system are occasionally associated with diseases
      such as Hand-Schuler-Christian disease, malignant fibrous histiocytoma,
      hyperlipidemia, and a complication of metabolic or storage disorders. However,
      until 2003, only a few cases of primary fibroxanthoma have been reported. We
      report a giant fibroxanthoma destroying the lateral skull base unaccompanied by a
      systemic or metabolic disease.

PMID- 15734534
TI  - Innate immune traits differ between Meishan and Large White pigs.
AB  - A panel of innate immune traits were compared between Meishan and Large White
      pigs. These pigs were of similar age and kept under the same environmental
      conditions to reduce non-genetically derived variation in immune traits. The
      animals were all apparently healthy and were not experimentally challenged with
      any pathogen during the study. The measures only required a small blood sample.
      Total white cell counts were similar between the pig breeds. However, the numbers
      of lymphocytes, neutrophils and monocytes differed significantly, with Meishans
      having higher neutrophil and monocyte counts and lower lymphocyte counts. Flow
      cytometric methods were used to determine quantitatively the characteristics and
      function of neutrophils and monocytes. Meishan neutrophils were smaller and less
      complex than Large White neutrophils, and phagocytosis of Escherichia coli and
      the ensuing oxidative burst was lower in Meishan neutrophils compared to Large
      White neutrophils. Monocyte phagocytosis of E. coli was significantly less than
      that of neutrophils in both breeds but the function of Meishan monocytes as
      measured by phagocytosis and tumour necrosis factor alpha (TNFalpha) release did
      not differ from that of Large White monocytes. Levels of acute phase proteins
      also differed between the breeds with a significantly higher proportion of
      Meishans having elevated serum amyloid A levels. However, Meishans had lower
      alpha(1)-acid glycoprotein levels than Large Whites and haptoglobin levels were
      similar. Such differences in innate immune traits may have implications in the
      resistance to infection by a broad range of pathogens and subsequent disease
      effects in these breeds. Further studies are warranted to investigate the genes
      underlying these traits.

PMID- 15734535
TI  - Cloning and sequence analysis of llama (lama glama) Th2 (IL-4, IL-10 and IL-13)
      cytokines.
AB  - This paper describes the cloning and sequence analysis of the cDNAs encoding the
      T helper (Th) 2 cytokines of llama including interleukin-4 (IL-4), IL-10 and IL
      13. The cDNAs encoding for IL-4, IL-10 and IL-13 were amplified using specific
      primers designed from reported sequences of bovine cytokine genes. The cDNAs for
      llama IL-4, IL-10 and IL-13 were found to be 402, 537 and 411 bp in length, with
      open reading frames encoding 133, 178 or 136 amino acids, respectively. Homology
      analyses of nucleotide and deduced amino acid sequences of llama IL-4, IL-10 and
      IL-13 and phylogenetic analysis based on their nucleotide sequences indicated the
      close relationship in these cytokine genes between llama and eutherian mammalian
      order Artiodactyla (pig, cattle) and Perissodactyla (horse).

PMID- 15734536
TI  - Identification of multiple linear epitopes of the plasminogen activator A (PauA)
      of Streptococcus uberis with murine monoclonal antibodies.
AB  - Streptococcus (S.) uberis is a common cause of mastitis in cattle. A protein
      (PauA) secreted by this bacterium is capable of activating plasminogen from sheep
      and cattle. The PauA first binds to bovine plasminogen (b-plg) to form a PauA
      plasminogen complex that subsequently binds to and activates b-plg to form
      plasmin. We have identified several linear epitopes of PauA that are recognized
      by murine monoclonal antibodies to PauA. Two of the monoclonal antibodies which
      neutralized the enzymatic activity of PauA, EC3 and 2.22, recognized common
      linear peptide sequences with similar charge and spacing patterns. These
      neutralization epitopes are located in the predicted alpha-domain of the PauA
      molecule. Further, these same epitopes are in critical structure/function domains
      identified in other studies. These characterizations may facilitate the design of
      an efficacious vaccine for streptococcal mastitis in the dairy cow.

PMID- 15734537
TI  - Inflammatory cell infiltration as an indicator of Staphylococcus aureus infection
      and therapeutic efficacy in experimental mouse mastitis.
AB  - Staphylococcus aureus intramammary colonization of the mouse mammary gland
      induces migration of polymorphonuclear neutrophils (PMNs) similar to that
      observed during bovine mastitis. In the present study, a method combining
      acridine orange staining, fluorescence microscopy and computer-assisted image
      analysis has been developed to quantitate PMN infiltration in a mouse model of
      mastitis. This was carried out using paraffin embedded sections, and using this
      method, we showed that the presence of PMNs increased with the number of bacteria
      present in tissues. Nearly 400 and 1100 times more PMNs were counted in the
      mammary gland tissue after 12 and 24 h of infection, respectively, compared to
      mice infected for 6 h. Treatment with the antibiotic cephapirin at 10 or 25 mg/kg
      reduced PMN infiltration by 71 and 85%, respectively. In conclusion, this method
      can be used to quantitate PMN infiltration as a marker of inflammation and
      bacterial burden in infected tissue sections.

PMID- 15734538
TI  - Effects of diet energy density and milking frequency in early lactation on tumor
      necrosis factor-alpha responsiveness in dairy cows.
AB  - A whole blood stimulation assay (WBA) with Escherichia coli lipopolysaccharide
      (LPS) and an enzyme-linked immunosorbent assay (ELISA) were established to
      measure the production of tumor necrosis factor-alpha (TNF-alpha) in bovine
      plasma. The assays were used to study the effect of time around parturition, and
      diet energy density, and milking frequency on TNF-alpha responsiveness of dairy
      cows in early lactation. Forty cows were included in a 2 x 2 factorial block
      design. One factor was high (H) versus low (L) diet energy density and the other
      factor was two versus three daily milkings. Blood samples were collected in weeks
      -3, -1, 2, 3, 5, 9, and 13 around parturition, and investigated for the TNF-alpha
      production ex vivo and CD14+ monocytes. The TNF-alpha response, CD14+ monocyte
      number, and CD14 expression level on monocytes were significantly increased in
      the weeks close to parturition. However, dips of varying sizes were observed for
      the measured parameters in week 3 after calving. Diet and milking frequency had
      no effect on the TNF-alpha response ex vivo or CD14 expression level on
      monocytes, but cows fed diet H had significantly higher numbers of CD14+
      monocytes than cows fed diet L. The WBA with LPS was a fast reliable method for
      repeated measurements of TNF-alpha responsiveness in cattle. Previous findings of
      increased TNF-alpha responses in periparturient cows were confirmed, whereas diet
      energy concentration and milking frequency had no effect on the TNF-alpha
      responsiveness in early lactation.

PMID- 15734539
TI  - Development of a monoclonal blocking ELISA for the detection of antibody to
      Mycoplasma bovis in dairy cattle and comparison to detection by PCR.
AB  - A monoclonal antibody blocking enzyme-linked immunosorbent assay (B-ELISA) was
      developed to detect antibodies to Mycoplasma bovis in cattle sera. The assay was
      highly specific and sensitive and there was no cross-reaction detected. This
      method revealed a high prevalence of antibodies (60%) to M. bovis in dairy cattle
      in North Queensland. The diagnostic potential of this B-ELISA for the detection
      of antibody to M. bovis was compared with its detection by PCR. There was a
      strong positive correlation between PCR and B-ELISA titers. Thus, the B-ELISA
      appears to be a valuable and reproducible tool in the serodiagnosis of M. bovis
      infection in cattle.

PMID- 15734540
TI  - Real-time RT-PCR quantification of mRNA encoding cytokines and chemokines in
      histologically normal canine nasal, bronchial and pulmonary tissue.
AB  - Cytokines and chemokines are likely to be involved in the pathogenesis of
      inflammatory diseases of the canine respiratory tract. The roles and relative
      amounts of these molecules have not yet been defined in the respiratory mucosa of
      normal dogs or dogs with naturally acquired respiratory inflammation. In the
      present study, real-time reverse transcriptase polymerase chain reaction (RT-PCR)
      assays were employed to quantify messenger RNA (mRNA) encoding the chemokines
      monocyte chemotactic protein (MCP)-2, eotaxin-2 and eotaxin-3, and the cytokines
      interleukin-4 (IL-4), IL-5, IL-6, IL-10, IL-12p40, IL-18, interferon-gamma (IFN
      gamma), tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor
      beta (TGF-beta) in normal nasal, bronchial and pulmonary tissues from puppies (n
      = 4) and from adult dogs (n = 7). There was no significant difference in the
      expression of any transcript between puppies and adult dogs at any of the
      anatomical sites examined. The expression of mRNA encoding eotaxin-2 and eotaxin
      3 increased significantly with progression from the nasal mucosa to pulmonary
      parenchyma but expression of MCP-2 mRNA did not show this trend. At all levels of
      the respiratory mucosa, the most abundant transcripts were those encoding IL-18
      and TGF-beta. Transcripts encoding IL-6, IL-10, IL-12 and TNF-alpha were
      approximately ten-fold less abundant, and IL-4, IL-5 and IFN-gamma were the least
      abundant templates. There was significantly different amount of mRNA encoding IL
      5, IL-18 and TNF-alpha between particular anatomical levels of the respiratory
      mucosa while the mRNA expression of the other cytokines was similar at all
      anatomical sites. The results of the present study will enable comparisons to be
      made with results obtained from similar samples obtained from dogs with nasal,
      bronchial or pulmonary diseases.

PMID- 15734541
TI  - Development and validation of puma (Felis concolor) cytokine and lentivirus real
      time PCR detection systems.
AB  - Studies of immune correlates of disease outcome associate humoral immune response
      mediated by T-helper 2 cytokines (IL-4, IL-10) with more virulent disease
      relative to a cell-mediated response driven by T-helper 1 cytokines (IL-2, IFN
      gamma), particularly in viral and other intra-cellular infections. Specifically,
      the kinetics of both human immunodeficiency virus (HIV) and feline
      immunodeficiency virus (FIV) infection are closely associated with Type 1 versus
      Type 2 cytokine profiles. Puma (Felis concolor) lentivirus (PLV) is closely
      related to FIV, but based on phylogenetic and clinical studies, is more ancient
      and less pathogenic. The aims of this study were to validate feline real-time PCR
      primer/probe systems for puma cytokines and PLV as sensitive, quantitative assays
      for use in investigations of PLV pathogenicity. We demonstrate that primer/probe
      systems for IL-4, IL-10, IFN-gamma, TNF-alpha, GAPDH, and the pol region of PLV
      1695 amplify puma cytokines and PLV-1695 with high amplification efficiency and
      sensitivity. Detection of PLV-1695 provirus in experimentally inoculated domestic
      cats proved to be of equivalent sensitivity, specificity, and positive and
      negative predictive value to co-culture of one million peripheral blood
      mononuclear cells (PBMC). Evaluation of cytokine induction during naturally
      occurring PLV infection will allow insight into mechanisms of host control
      associated with apathogenic infection. In addition, determination of viral loads
      during different stages of PLV infection or in different tissues from domestic
      cats or pumas will further elucidate capacity of these viruses to replicate and
      establish infection.

PMID- 15734542
TI  - Assessment in mice of vapA-DNA vaccination against Rhodococcus equi infection.
AB  - There is a need to produce a vaccine against Rhodococcus equi pneumonia in foals
      in which immunity against infection is largely based on a type 1, cell-mediated,
      immune response. The VapA protein of the virulence plasmid of R. equi is highly
      immunogenic. To assess the potential of vapA-DNA to produce immunity, C57BL/6 and
      BALB/c mice were immunized with a DNA vaccine constructed from vapA incorporated
      into pcDNA3.1. The plasmid construct expressed VapA in a COS-7 cell line.
      Intramuscular immunization of mice resulted in enhanced clearance of R. equi from
      the liver of intravenously challenged mice compared to non-immunized controls.
      This effect was more marked when pORF-IL-12, a plasmid expressing murine IL12,
      was included with the vaccine. Antibody developed to VapA, with an IgG2a response
      being more marked in mice immunized with pcDNA-vapA than in non-immunized or in
      mice immunized with the mixed vapA and IL-12 plasmid constructs. In conclusion,
      this study has shown for the first time that DNA immunization with vapA enhances
      the immune responses of mice against R. equi infection, that the IgG subisotype
      response is consistent with a type 1-based immune response, and that this can be
      enhanced by injection of the IL-12 gene.

PMID- 15734543
TI  - Cellular immunophenotyping of exfoliative dermatitis in canine leishmaniosis
      (Leishmania infantum).
AB  - Lymphocyte subsets, major histocompatibility complex (MHC)-II expressing cells
      and number of amastigotes in the epidermis and dermis were investigated
      immunohistochemically in 48 dogs with patent leishmaniosis, with or without
      exfoliative dermatitis (ED) to study the immunopathogenesis of this common
      cutaneous form of the disease. Skin biopsies were obtained and compared for ED
      sites (group A, n = 26), normal-appearing skin from the same animals (group B, n
      = 24), and leishmanial dogs not exhibiting ED (group C, n = 22), and normal
      controls (group D, n = 22). The CD3+, CD45RA+, CD4+, CD8+ (CD8a+), CD21+, and MHC
      II+ cells and leishmania amastigotes were identified immunohistochemically and
      counted with the aid of an image analysis system. Pyogranulomatous to
      granulomatous dermatitis, expressed in various histopathological patterns, was
      noticed in all groups A and B and in half of group C dogs. In the epidermis, the
      low number of T-cells and their subsets did not differ significantly between
      groups A and B, but CD8+ outnumbered CD4+ lymphocytes in both groups. MHC-II+
      expression on epidermal keratinocytes was intense in the skin with and without
      lesions from dogs with ED but not in group C dogs. CD3+, CD8+ and MHC-II+ cells
      were fewer in group C compared to group A and B dogs. In the dermis, CD3+ cells
      in group A animals were mainly represented by the CD8+. CD45RA+ and CD21+ cells
      were also seen in high numbers. MHC-II expression, potentially in lymphocytes,
      fibroblasts, dendritic cells, and macrophages was intense. The numbers of all
      cellular subpopulations in the dermis were significantly different between the
      groups, being highest in group A and lowest in group D. In sebaceous adenitis
      sites, CD4+ outnumbered CD8+ cells in contrast to the neighbouring dermis and the
      epidermis. The number of CD21+ and CD45RA+ cells was much lower in the inflamed
      sebaceous glands compared to the dermis. Finally, the number of amastigotes in
      the normal-appearing skin was significantly higher in the ED dogs (group B) than
      in those not exhibiting this cutaneous form of the disease (group C).

PMID- 15734544
TI  - Lymphatic organ development in dogs: major lymphocyte subsets and activity.
AB  - In the present study, we have characterized lymphocyte subsets and activity in
      peripheral blood, spleen, mesenteric and popliteal lymph nodes in pups from birth
      till the age of one month and compared the results with the situation in the
      group of three adult dogs. In neonatal pups, lower numbers of CD3(+) T-cells were
      detected in both the spleen and peripheral blood than in lymph nodes. In contrast
      to the other compartments, CD21(+) B-cells prevailed in the spleen, which
      resulted in low values (<1) of the CD3(+)/CD21(+) ratio. Low numbers of CD8(+)
      lymphocytes were characteristic in all compartments immediately after birth;
      consequently a high CD4(+)/CD8(+) ratio has been calculated. Postnatal
      development was characterized by an increasing frequency of CD8(+) lymphocytes in
      all organs studied. Another typical feature of the early period of life was a
      relative decrease of B-cell numbers, which was compensated by an increasing
      proportion of T-lymphocytes, particularly in the peripheral blood and spleen. DNA
      synthesis in newborn pups' cells as measured by in vitro thymidine incorporation
      was surprisingly high in non-stimulated control samples, notably in the spleen.
      Further development of lymphocyte activity was characterized by the decline in
      spontaneous activity in all organs. Stimulation indices upon mitogen-induced
      proliferation increased proportionally to the decrease in spontaneous activity.
      Based on our experimental data, we have concluded that pups are born with a
      relatively competent immune system the structure of which, however, markedly
      develops during a few postnatal weeks.

PMID- 15734545
TI  - IgE reactivity to vaccine components in dogs that developed immediate-type
      allergic reactions after vaccination.
AB  - Allergic reactions after vaccination are considered as an important practical
      problem in dogs; however, their immunological mechanism has not been well
      understood. The present study was designed to investigate the relationship
      between IgE reactivity to the vaccines and immediate-type allergic reactions
      after vaccination in dogs. Sera from 10 dogs that developed immediate-type
      allergic reactions such as circulatory collapse, cyanosis, dyspnea, facial edema,
      and vomiting within 1h after vaccination with non-rabies monovalent or combined
      vaccines and sera from 50 dogs that did not develop allergic reactions after
      vaccination were collected. Serum IgE reactivity to the injected vaccines was
      measured by fluorometric ELISA using a mouse monoclonal anti-dog IgE antibody.
      Then, IgE reactivity to fetal calf serum (FCS) and stabilizer proteins (gelatin,
      casein, and peptone) included in the vaccines was measured in sera that had high
      levels of IgE to the vaccines. Levels of serum specific IgE to the vaccines in
      dogs with immediate-type allergic reactions (59-4173 fluorescence units [FU],
      mean +/- S.D.: 992.5 +/- 1181.9 FU) were significantly higher than those in
      control dogs (38-192 FU, 92.4 +/- 43.3 FU) (P < 0.001). Of the eight dogs that
      developed immediate-type allergic reactions and had high levels of serum specific
      IgE to the vaccines, seven had specific IgE directed to FCS. The IgE reactivity
      to the vaccines in sera from these dogs was almost completely inhibited by FCS.
      The other one dog had serum IgE directed to gelatin and casein included in the
      vaccine as stabilizers. The results obtained in this study suggest that immediate
      type allergic reactions after vaccination in dogs were induced by type I
      hypersensitivity mediated by IgE directed to vaccine components. In addition,
      FCS, gelatin, and casein included in vaccines could be the causative allergens
      that induced immediate-type allergic reactions after vaccination in dogs.

PMID- 15734546
TI  - Goat endothelial cells may be infected in vitro by transmigration of caprine
      arthritis-encephalitis virus-infected leucocytes.
AB  - The caprine arthritis-encephalitis lentivirus (CAEV) causes a lifelong persistent
      infection in goats, and induces infiltrations of leucocytes and tissue
      reorganization in target organs, with a cyclical pattern of viral expression. The
      mammary gland is an important site of infection, associated with mother-to-kid
      transmission by infected cells in colostrum and milk. The monocyte/macrophage is
      the principal target cell, but other cell types, including epithelial and
      endothelial cells and fibroblasts, are susceptible to in vitro infection with
      varying levels of viral replication. Such cells, perhaps at specific
      differentiation states, might play a role in the regulation and transfer of in
      vivo infection in target organs. In this paper we describe the in vitro infection
      of endothelial cell monolayers by the transmigration of monocytes carrying the
      CAEV provirus. The infected endothelial cells progress to expression of the viral
      p30 capsid antigen, suggesting viral proliferation. Such a process occurring in
      vivo during angiogenesis and leucocyte homing to the mammary gland in the final
      third of mammogenesis, might contribute to viral spread in this crucial target
      organ.

PMID- 15734547
TI  - Placental transfer of immunoglobulins in cattle infected with Schistosoma
      mattheei.
AB  - Although the epitheliochorial placenta of ruminants does not allow passage of
      immunoglobulins from dam to foetus specific antibodies have been detected at
      birth in calves born to Schistosoma mattheei-infected cows. The present study
      determined the prevalence of calves born with specific antibodies for S. mattheei
      and the origin of these antibodies. For the determination of the prevalence, 100
      calves born to infected mothers in an endemic area (Zambia) were examined, 24
      were seropositive. To study the origin of these antibodies placentomes of 40
      naturally S. mattheei-infected cows were examined for the presence of schistosome
      eggs and lesions which could explain foetal priming and/or leakage of maternal
      antibodies and/or antigen into the foetus. Tissue damage and schistosome eggs
      were observed on the maternal as well as the foetal side of the placentomes. In
      order to determine the specific nature of the antibody response, antibody
      profiles against soluble adult worm antigen preparation (SWAP) of S. mattheei
      were compared by Western blot between dams and their newborn calves (n = 8). The
      specific recognition profiles were identical for the seropositive calves and
      their dams on SWAP mattheei. Identical recognition profiles between dams and
      calves were also observed when sera were analysed on Escherichia coli, a pathogen
      of which the foetus should be free, and would indicate passive antibody transfer
      from the dam. In conclusion, the present study shows that S. mattheei could
      induce placentome lesions and that eggs can cross the placenta. Consequently,
      foeti can come into contact with S. mattheei antigens in utero, and might also
      contain maternal antibodies from leakage through placentome lesions. As such, the
      infection status of the mother could have far reaching effects on the
      immunological status of her offspring and modify their reaction upon infection.

PMID- 15734548
TI  - A peptide vaccine administered transcutaneously together with cholera toxin
      elicits potent neutralising anti-FMDV antibody responses.
AB  - In this study a synthetic peptide representing residues 141-159 from the GH loop
      of VP1 protein of foot-and-mouth disease virus was tested for its capacity to
      elicit virus neutralising antibodies in mice after transcutaneous immunisation.
      Topical application of the peptide conjugated to bovine serum albumin together
      with cholera toxin as an adjuvant elicited anti-peptide antibody responses with
      strong virus neutralising activity. The combination of cholera toxin with an
      immunostimulatory CpG motif resulted in the induction of IgG1 and IgG2a anti
      peptide antibodies with significantly enhanced virus neutralising activity. To
      shed more light on the mechanisms of cholera toxin adjuvanticity we demonstrated
      its binding to keratinocytes via GM(1)-gangliosides. This was followed by an
      increase of the intracellular cAMP and the rapid diffusion of cholera toxin
      throughout the epidermis. These findings demonstrate that peptide-based vaccines
      when combined with the appropriate adjuvant(s) can elicit potent virus
      neutralising antibody responses after transcutaneous immunisation. However,
      experiments in target species will be required to confirm the potential of this
      simple vaccination procedure in livestock.

PMID- 15734549
TI  - Localization of porcine CD29 transcripts and protein in pig cells and tissues by
      RT-PCR and immunohistochemistry.
AB  - Integrins are heterodimeric cell adhesion proteins with major roles in a variety
      of biological processes ranging from cell migration to tissue organization,
      immune and non-immune defense mechanisms and oncogenic transformation. Members of
      the beta(1) integrin subfamily are composed of a beta(1) subunit (CD29) non
      covalently associated with different alpha subunits to constitute a group of
      transmembrane glycoproteins that participate in many physiologically important
      events. Here, we have studied the CD29 expression in porcine tissues and cells at
      two different levels: expression of the CD29 mRNA by RT-PCR and localization of
      the protein by immunohistochemistry. CD29 transcripts were detected in a variety
      of tissues and cells: platelets, PBMC, granulocytes, alveolar macrophages, smooth
      muscle, intestine, lung, liver, spleen, lymph node, skin, testis, heart, kidney
      and bone marrow. Our results suggest that CD29 gene transcription occurs in all
      organs examined, although with different intensities. The precise localization of
      CD29 protein in paraffin-embedded tissues was detected by using a specific
      polyclonal antibody indicating that its expression is limited to smooth muscle,
      epithelium cells, endothelium of blood vessels and myeloid cells and is no
      detectable in cells of the lymphoid lineage. The distribution of the CD29 in
      normal tissues provide insight into the physiological function of the porcine
      beta(1) integrins and should be of importance in understanding the role of this
      integrin family in pathological processes.

PMID- 15734550
TI  - Effects of polyunsaturated fatty acids on the proliferation of mitogen stimulated
      bovine peripheral blood mononuclear cells.
AB  - The present study aimed at analysis of the effects of polyunsaturated fatty acid
      (PUFA), linoleic acid (LA, C18:2n - 6) and linolenic acid (LNA, C18:3n - 3) on
      bovine peripheral blood mononuclear cells (PBMC) in vitro. Both mitogen (ConA)
      induced proliferative lymphocyte responsiveness during 4 days of culture and
      eicosanoid (prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4))) production
      during 36 h were determined in relation to the absence or presence of various
      concentrations of LA and LNA (0, 1, 5, 25, 125 and 250 microM). Mitogen-driven
      proliferative responses of lymphocytes tended to be uninfluenced in the presence
      of lower concentrations of LA, whereas significant inhibition was observed at the
      higher concentrations of LA (125 and 250 microM). However, increasing amounts of
      LNA did not affect the proliferation. ConA stimulation induced a clear PGE(2)
      response, which significantly decreased in the presence of 250 microM of LA. In
      addition, increasing amounts of LNA, but not LA, led to a significant decrease in
      LTB(4) levels. However, The production of LTB(4) did not alter due to mitogenic
      stimulation. In conclusion, the present study shows that bovine mononuclear cells
      may functionally be influenced by the presence of PUFA in their environment.
      Further studies need to be conducted to clarify in vivo consequences of these
      findings in a situation of PUFA enriched rations in ruminants.

PMID- 15734551
TI  - Engineering regulatory RNAs.
AB  - RNA has long been a favoured medium for in vitro evolution and engineering.
      Functional RNAs produced in vitro can bind small molecules (aptamers), possess
      catalytic activity (ribozymes) or do both (aptazymes). A plethora of recent work
      has shown similar strategies used naturally for gene regulation in bacteria.
      Interest in these natural systems has inspired an effort to engineer and evolve
      this activity in vivo. A recent paper by Isaacs et al. describes the engineering
      and in vivo activity of a small RNA that removes translation inhibition by
      binding the 5' untranslated region of its target mRNA and making the ribosome
      binding site accessible.

PMID- 15734552
TI  - Digital biology: an emerging and promising discipline.
AB  - This article examines the role of computation and quantitative methods in modern
      biomedical research to identify emerging scientific, technical, policy and
      organizational trends. It identifies common concerns and practices in the
      emerging community of computationally-oriented bio-scientists by reviewing a
      national symposium, Digital Biology: the Emerging Paradigm, held at the National
      Institutes of Health in Bethesda, Maryland, November 6th and 7th 2003. This
      meeting showed how biomedical computing promises scientific breakthroughs that
      will yield significant health benefits. Three key areas that define the emerging
      discipline of digital biology are: scientific data integration, multi-scale
      modeling and networked science. Each area faces unique technical challenges and
      information policy issues that must be addressed as the field matures. Here we
      summarize the emergent challenges and offer suggestions to academia, industry and
      government on how best to expand the role of computation in their scientific
      activities.

PMID- 15734553
TI  - Regulating genomics in the 21st century: from logos to pathos?
AB  - There is currently an important change in the governance of genomics. In the
      past, much of the regulatory discussion about genomics has focused on issues of
      risk. Today, a new discussion is evolving that emphasizes the uncertainties
      involved in the development and diffusion of genomics into society. The
      increasing importance of emotional language and the focus on trust in the
      discussion about genomics reflects the attempt to substitute for the shortcomings
      of logos with ethos and pathos.

PMID- 15734554
TI  - New directions in incidence-dose modeling.
AB  - Many cellular responses are quantal; that is, they either take place or they do
      not. Examples of "either-or" responses include cell replication, differentiation
      and apoptosis. Surprisingly, induction of suites of genes and coordinated
      phenotypic changes in cells are also often quantal, where embedded molecular
      circuitry creates on-off switches. Mechanistic incidence-dose (ID) models need to
      account for the quantal characteristics of cellular switches that contribute, in
      turn, to dose thresholds and to the incidence of biological responses in
      individuals. Interdisciplinary systems biology approaches create mechanistic ID
      models based on: (i) detailed knowledge of the cellular circuitry controlling
      signal transduction; (ii) evolving biological modeling tools describing cellular
      circuits and their perturbations by chemicals and (iii) high throughput, high
      coverage "omic" screens for examining cell signaling pathways and biological
      responses. These interdisciplinary approaches should produce novel, quantitative
      ID models for biological responses and greatly improve the biological basis of
      safety and risk assessments.

PMID- 15734555
TI  - Immune modulation for prevention of type 1 diabetes mellitus.
AB  - Prevention of type 1 diabetes mellitus requires early intervention in the
      autoimmune process directed against beta cells of the pancreatic islets of
      Langerhans. This autoimmune inflammatory process is thought to be caused by the
      effect of Th1 cells and their secreted cytokines (e.g. interferon) and to be
      suppressed by Th2-secreted anti-inflammatory cytokines (e.g. IL-4, IL-10).
      Various methods aimed specifically at halting or modulating this response have
      been attempted. An alternative method is the re-induction of tolerance towards
      the putative self antigen that causes the disease. Proposed antigens such as
      insulin, glutamic acid decarboxilase (GAD) and the heat shock protein 60 (Hsp60)
      derived peptide 277 have been used successfully in murine diabetes models and in
      initial clinical trials in early diabetes patients. Here, we review the results
      of these trials.

PMID- 15734556
TI  - Accessing microbial diversity for bioremediation and environmental restoration.
AB  - Biological methods for decontamination promise an improved substitute for
      ineffective and costly physico-chemical remediation methods, although so far only
      a fraction of the total microbial diversity (i.e. the culturable fraction with
      metabolic potential) has been harnessed for this purpose. Exploring and
      exploiting the "overlooked" genetic resource might ameliorate concerns associated
      with the degradation of recalcitrant and xenobiotic pollutants that are not
      degraded or only poorly degraded by known culturable bacteria. Recent advances in
      the molecular genetics of biodegradation and in knowledge-based methods of
      rational protein modification provide insight into the development of "designer
      biocatalysts" for environmental restoration. The application of such genetically
      engineered microorganisms (GEMs) in the environment has been limited, however,
      owing to the risks associated with uncontrolled growth and proliferation of the
      introduced biocatalyst and horizontal gene transfer. Programming rapid death of
      the biocatalyst soon after the depletion of the pollutant could minimize the
      risks in developing these technologies for successful bioremediation.

PMID- 15734557
TI  - Physicochemical perspectives on DNA microarray and biosensor technologies.
AB  - Detection and sequence-identification of nucleic acid molecules is often
      performed by binding, or hybridization, of specimen "target" strands to
      immobilized, complementary "probe" strands. A familiar example is provided by DNA
      microarrays used to carry out thousands of solid-phase hybridization reactions
      simultaneously to determine gene expression patterns or to identify genotypes.
      The underlying molecular process, namely sequence-specific recognition between
      complementary probe and target molecules, is fairly well understood in bulk
      solution. However, this knowledge proves insufficient to adequately understand
      solid-phase hybridization. For example, equilibrium binding constants for solid
      phase hybridization can differ by many orders of magnitude relative to solution
      values. Kinetics of probe-target binding are affected. Surface interactions,
      electrostatics and polymer phenomena manifest themselves in ways not experienced
      by hybridizing strands in bulk solution. The emerging fundamental understanding
      provides important insights into application of DNA microarray and biosensor
      technologies.

PMID- 15734558
TI  - The past, present and future of cell-free protein synthesis.
AB  - Recent technical advances have revitalized cell-free expression systems to meet
      the increasing demands for protein synthesis. Cell-free systems offer several
      advantages over traditional cell-based expression methods, including the easy
      modification of reaction conditions to favor protein folding, decreased
      sensitivity to product toxicity and suitability for high-throughput strategies
      because of reduced reaction volumes and process time. Moreover, improvements in
      translation efficiency have resulted in yields that exceed a milligram of protein
      per milliliter of reaction mix. We review the advances on this expanding
      technology and highlight the growing list of associated applications.

PMID- 15734559
TI  - Painting protein misfolding in the cell in real time with an atomic-scale brush.
AB  - The direct observation of specific biochemical events in living cells is now
      possible as a result of combined advances in molecular biology and fluorescence
      microscopy. By genetically encoding the source of a unique spectroscopic signal,
      target proteins can be selectively detected within the complex cellular
      environment, with limited interference from background signals. A recent study
      takes advantage of arsenical reagent-based methodologies to monitor in vivo
      protein misfolding and inclusion body formation in real time. This approach
      promises to yield important information on the kinetics of aggregate formation in
      living cells and its relation to the time-course of protein expression and post
      translational processing. The ability to follow protein self-association in real
      time accurately from its early stages is unique to this method, and has far
      reaching implications for both biotechnology and misfolding-based disease.

PMID- 15734560
TI  - Aspergillus flavus growth in the presence of chemical preservatives and naturally
      occurring antimicrobial compounds.
AB  - The combined effects of water activity ([a(w)] 0.99 or 0.95), pH (4.5 or 3.5) and
      antimicrobial agent (potassium sorbate, sodium benzoate, sodium bisulfite,
      carvacrol, citral, eugenol, thymol, or vanillin) concentration (0, 100, 200 up to
      1800 ppm) on the growth of Aspergillus flavus were evaluated in potato dextrose
      agar (PDA). Mold spore germination time and radial growth rates (RGR) were
      significantly (p<0.05) affected by the variables. For equal antimicrobial
      concentration, reduction in pH or a(w) had important effects, lowering RGR and
      delaying germination time. Depending on a(w) and pH, increase in antimicrobial
      concentration slightly reduced RGR until a critical concentration where RGR was
      drastically reduced or mold growth was inhibited. Germination time increased as
      antimicrobial agent concentration increased and when a(w) and pH decreased.
      Important antimicrobial differences were observed, being, in general, the natural
      antimicrobials less pH-dependent than chemical preservatives. A. flavus exhibited
      higher sensitivity to thymol, eugenol, carvacrol, potassium sorbate, sodium
      bisulfite, and sodium benzoate (at pH 3.5) than to vanillin or citral.

PMID- 15734561
TI  - Behavior of Yersinia enterocolitica and Salmonella typhimurium in Crottin goat's
      cheese.
AB  - In order to evaluate the behavior of Yersinia enterocolitica and Salmonella
      typhimurium in Crottin goat's cheese, inoculated products stored at 5, 15 and 25
      degrees C were analysed together with chemical and microbiological
      characteristics of the cheese. In general, low counts of microorganisms were
      detected. None of the samples showed the presence of Escherichia coli, Salmonella
      spp. or Y. enterocolitica. In the inoculation tests, Y. enterocolitica and S.
      typhimurium were inhibited during storage; nevertheless, these bacteria survived
      for extensive periods. The counts at the end of the experiments at 5 and 15
      degrees C were high, indicating that contamination with high bacterial numbers
      represents a potential health hazard. The primary mathematical models used to
      analyse the behavior of Y. enterocolitica and S. typhimurium were the Vitalistic,
      Gompertz's empirical and Churchill's model. The mean square error was calculated
      for the three models in order to evaluate the goodness-of-fit of each one. For Y.
      enterocolitica, the Vitalistic model was the best at the three temperatures. For
      S. typhimurium, there was no significant difference between the three models at 5
      and 15 degrees C; the Churchill model was clearly the best at 25 degrees C. These
      results confirm that, in order to predict the risk of transmission of pathogenic
      microorganisms in foods using mathematical models, it is essential to analyse
      their behavior in specific foods.

PMID- 15734562
TI  - Identification of yeast strains isolated from marcha in Sikkim, a microbial
      starter for amylolytic fermentation.
AB  - Marcha or murcha is a traditional amylolytic starter used to produce sweet-sour
      alcoholic drinks, commonly called jaanr in the Himalayan regions of India, Nepal,
      Bhutan, and Tibet (China). The aim of this study was to examine the microflora of
      marcha collected from Sikkim in India, focusing on yeast flora and their roles.
      Twenty yeast strains were isolated from six samples of marcha and identified by
      genetic and phenotypic methods. They were first classified into four groups
      (Group I, II, III, and IV) based on physiological features using an API test.
      Phylogenetic, morphological, and physiological characterization identified the
      isolates as Saccharomyces bayanus (Group I); Candida glabrata (Group II); Pichia
      anomala (Group III); and Saccharomycopsis fibuligera, Saccharomycopsis
      capsularis, and Pichia burtonii (Group IV). Among them, the Group I, II, and III
      strains produced ethanol. The isolates of Group IV had high amylolytic activity.
      Because all marcha samples tested contained both starch degraders and ethanol
      producers, it was hypothesized that all four groups of yeast (Group I, II, III,
      and IV) contribute to starch-based alcohol fermentation.

PMID- 15734564
TI  - The mathematical properties of the quasi-chemical model for microorganism growth
      death kinetics in foods.
AB  - Knowledge of the mathematical properties of the quasi-chemical model [Taub,
      Feeherry, Ross, Kustin, Doona, 2003. A quasi-chemical kinetics model for the
      growth and death of Staphylococcus aureus in intermediate moisture bread. J. Food
      Sci. 68 (8), 2530-2537], which is used to characterize and predict microbial
      growth-death kinetics in foods, is important for its applications in predictive
      microbiology. The model consists of a system of four ordinary differential
      equations (ODEs), which govern the temporal dependence of the bacterial life
      cycle (the lag, exponential growth, stationary, and death phases, respectively).
      The ODE system derives from a hypothetical four-step reaction scheme that
      postulates the activity of a critical intermediate as an antagonist to growth
      (perhaps through a quorum sensing biomechanism). The general behavior of the
      solutions to the ODEs is illustrated by several examples. In instances when
      explicit mathematical solutions to these ODEs are not obtainable, mathematical
      approximations are used to find solutions that are helpful in evaluating growth
      in the early stages and again near the end of the process. Useful solutions for
      the ODE system are also obtained in the case where the rate of antagonist
      formation is small. The examples and the approximate solutions provide guidance
      in the parameter estimation that must be done when fitting the model to data. The
      general behavior of the solutions is illustrated by examples, and the MATLAB
      programs with worked examples are included in the appendices for use by
      predictive microbiologists for data collected independently.

PMID- 15734563
TI  - Acid-adaptation does not increase the resistance of Listeria monocytogenes to
      irradiation in a seafood salad.
AB  - Stress adaptation of microbial cells enables the cells to survive better when
      they are subsequently exposed to other types of stresses. In the food industry,
      pathogens are commonly stressed during food processing and this is a concern
      where pathogens such as Listeria monocytogenes are involved. Research was
      conducted to determine if acid adaptation of L. monocytogenes provides resistance
      to ionizing irradiation. Three different strains of L. monocytogenes were acid
      adapted using three different acids (acetic, citric, lactic) in Tryptic Soy
      Broth, at a pH 5.5 for 1 h, 4 h, or continuous acid exposure. The acid-adapted L.
      monocytogenes were then exposed to a low level of gamma irradiation (0.59-0.72
      kGy) along with a non-acid adapted L. monocytogenes control. In a test tube
      study, the 1-h acetic acid-adapted L. monocytogenes strains showed the greatest
      difference from the control, a reduced kill of 1.1 log CFU/g but this difference
      was not significant by ANOVA (p=0.054). The reduction achieved after 4 h and
      continuous acid exposure also did not significantly differ from the control. To
      determine whether acid adaptation affected radiation resistance within a food
      product, a refrigerated storage shelf-life study was completed. Acetic acid was
      used to acid adapt a three-strain cocktail of L. monocytogenes for a period of 1
      h. The organisms were then inoculated into a seafood salad (pH 5.15) and
      subsequently exposed to low dose gamma irradiation (0.7 to 4.5 kGy). L.
      monocytogenes was reduced or eliminated by irradiation regardless of acid
      adaptation; no increased resistance was observed.

PMID- 15734565
TI  - Natural occurrence of Fusarium and subsequent fumonisin contamination in
      preharvest and stored maize in Benin, West Africa.
AB  - The natural occurrence of Fusarium and fumonisin contamination was evaluated from
      1999 to 2003 in both preharvest and stored maize produced by small-scale farmers
      in four agroecological zones of Benin. Mycological analyses revealed a
      predominance of both Fusarium and Aspergillus in maize samples compared to other
      genera. The two Fusarium species most commonly isolated from maize were Fusarium
      verticillioides (68%) and Fusarium proliferatum (31%). Atypical isolates of F.
      verticillioides with some characteristics of Fusarium andiyazi but apparently
      closer to F. verticillioides, because the isolates were all high fumonisin
      producers, were also found only on preharvest maize. Study of F. verticillioides
      strains showed the presence of extremely high fumonisin producers in Benin with
      total fumonisin levels ranging from 8240 to 16,690 mg/kg. Apart from 2002-2003,
      Fusarium occurrence was not significantly different from one zone to another,
      although a slight decrease was observed from south, humid, to north, drier.
      Fusarium occurrence varied somewhat from one season to another. It significantly
      decreased over the 6 months of storage. Widespread fumonisin occurrence in maize
      was observed. Most of the maize samples collected were found positive for
      fumonisin with levels ranging from not detected to 12 mg/kg in 1999-2000, 6.7
      mg/kg in 2000-2001 and 6.1 mg/kg in 2002-2003. Fumonisin levels in maize were
      found to be significantly higher in the two southern zones during all the
      surveys. The highest mean total fumonisin level was detected in 1999-2000 in
      maize samples from the southern Guinea Savannah (SGS) (12 mg/kg), whereas in both
      2000-2001 and 2002-2003, it was in samples from the forest mosaic savannah (FMS)
      (6.7 and 6.1 mg/kg, respectively). Fumonisin levels varied from one season to
      another and, throughout the storage time, showing a decreasing trend in each
      zone. However, this decrease was not significant every season. An increasing
      trend was observed during some seasons in the SGS and northern Guinea Savannah
      (NGS) zones. The results of this study emphasise that farmers and consumers, not
      only in Benin but also in other West African countries, should be alerted to the
      danger of fumonisin contamination in maize.

PMID- 15734566
TI  - Preparation of gold-labeled antibody probe and its use in immunochromatography
      assay for detection of aflatoxin B1.
AB  - Preparation of an antibody-colloidal gold probe (conjugate) specific to aflatoxin
      B1 (AFB1) and its use in developing a rapid AFB1 diagnostic method was presented
      in this paper. Monodispersional nanogold colloid was synthesized and preparation
      of nanogold-labeled polyclonal antibody probe to aflatoxin B1 under friendly and
      optimal condition. Combination of antibody with nanogold particles was also
      characterized by UV-visible (UV-vis) light absorption spectra, transmission
      electron microscopy (TEM), fluorescence spectroscopy, titers, cross reactivity
      and stability measurements. Furthermore, nanogold-labeled probe was used to
      develop an immunochromatographic (IC) method for aflatoxin B1 analysis. With this
      method, analysis could be completed in less than 10 min. Detection time was
      reduced 6-10 times comparative with ELISA. With visual observation, lower test
      limit was found to be around 2.5 ng/ml aflatoxin B1 standard solution, which was
      increased to two times of ELISA.

PMID- 15734567
TI  - Morphological, chemical and molecular differentiation of Fusarium equiseti
      isolated from Norwegian cereals.
AB  - The morphological variation, secondary metabolite profiles and restriction
      fragment length polymorphisms (RFLPs) of PCR amplified intergenic spacer (IGS)
      ribosomal DNA (rDNA) were studied in 27 isolates of Fusarium equiseti, 25
      isolated from Norwegian cereals and 2 from soil obtained from the IBT culture
      collection (BioCentrum, Technical University of Denmark). All 27 isolates were
      tested for production of fusarochromanone (FUSCHR), zearalenone (ZEA) and the
      trichothecenes: 15-monoacetoxy-scirpentriol (MAS), diacetoxy-scirpenol (DAS), T-2
      and HT-2 toxins, T2-triol, neosolaniol (NEO), deoxynivalenol (DON), nivalenol
      (NIV) and 4-acetylnivalenol (Fus-X). The trichothecenes were analysed by GC-MS in
      a selected ion monitoring mode, while FUSCHR was determined by ion pair HPLC with
      fluorometric detection and production of ZEA by TLC. For amplification of IGS
      rDNA primers CNL12 and CNS1 were applied. IGS rDNA was digested with the four
      restriction enzymes: AvaII, CfoI, EcoRI and Sau3A. In addition, we sequenced the
      IGS rDNA region of three of the Norwegian isolates. There were two morphological
      types among the Norwegian strains of F. equiseti, type I with short apical cells
      (dominating) and type II with long apical cells, with four haplotypes identified
      based on the RFLP data. Variation in secondary metabolite profiles within and
      between the morphological groups was observed and the levels of produced toxins
      were: FUSCHR 3000-42,500 and 25-30 ng/g, NIV 20-2500 and 120-700 ng/g, FUS-X 20
      15,000 and 0 ng/g, DAS 30-7500 and 0-600 ng/g, and MAS 10-600 and 0-500 ng/g, for
      strains with short and long apical cells, respectively. NEO was detected in 16/27
      strains tested (all morphotype I). All but four strains of type I (these four
      lacked a restriction site for EcoRI) had identical RFLP profiles. The isolates of
      type II had two haplotypes. The IGS sequence similarity data indicated
      differences between these morphotypes corresponding to two separate lineages
      apparently at the species level.

PMID- 15734568
TI  - The effect of substrate on mycotoxin production of selected Penicillium strains.
AB  - Analytical methods are presented for detecting simultaneously 11 fungal
      metabolites (aflatoxins B1, B2, G1 and G2, citrinin, cyclopiazonic acid,
      mycophenolic acid, ochratoxin A, penicillic acid, penitrem A and roquefortine C)
      on different matrices. The methods were applied to determine the mycotoxins
      produced by different Penicillium crustosum, Penicillium nordicum and Penicillium
      verrucosum strains on yeast extract sucrose (YES) agar and cheese and bread
      analogues and are based on high-performance liquid chromatography (HPLC) and
      photodiode array detection (PDA). The growth substrate had a distinctive effect
      on the mycotoxin production ability of the fungi examined. The P. crustosum
      strains produced roquefortine C on all the substrates, with the highest amounts
      being detected on the cheese analogue. Penitrem A was synthesised on the cheese
      analogue only. The strains of P. verrucosum produced exclusively citrinin on YES,
      but both ochratoxin A and citrinin were detected in considerable amounts on the
      bread analogue. On the bread, toxin profiles varied significantly between the
      individual P. verrucosum strains. The cheese analogue was not favourable for the
      mycotoxin production of this species. The growth substrate had the least effect
      on the toxin production of the P. nordicum strains, which synthesised ochratoxin
      A in moderate amounts on all three media.

PMID- 15734569
TI  - Mycological survey of ripped service tree fruits (Sorbus domestica L.) with an
      emphasis on toxinogenic fungi.
AB  - To investigate a possible incidence of microscopic fungi in ripped service tree
      (Sorbus domestica L.) fruits, a mycological survey was carried out during October
      November 2003 in Slovakia. This rare kind of fruit is renowned for its
      significant curative actions in various human and animal diseases. The study
      revealed that all 24 surface sterilized fruits analysed were contaminated with
      fungi. The most dominant endogenous contaminant encountered was Cladosporium
      cladosporioides (Fres.) de Vries followed by Alternaria alternata (Fr.) Keissler
      and Penicillium expansum Link with 88%, 63% and 54% frequency, respectively.
      Furthermore, 24 other fungal species were associated with the fruits as well. P.
      expansum (40), P. carneum (Frisvad) Frisvad/Penicillium paneum Frisvad (35) and
      P. griseofulvum Dierckx (6) isolates recovered from the fruits were screened by
      an agar plug method for production of mycotoxin patulin, all with positive
      results. In addition, citrinin, griseofulvin and zearalenon production by
      appropriate species isolates were detected. Despite of a limited number of
      samples of the service tree fruits examined during this study, it was concluded
      that the ripening of service tree fruits is accompanied with the presence of
      typical rotting-fungi as well as of some others, which have not previously been
      reported in connection with fruit. Furthermore, it was suggested that the ripped
      service tree fruits should be considered as a potential source of significant
      fungal secondary metabolites including mycotoxins. Secondary metabolite profiles
      of the species identified during the study were included here.

PMID- 15734570
TI  - Transfer RNA gene recruitment in mitochondrial DNA.
AB  - Transfer RNA (tRNA) is the adaptor molecule that mediates recognition of the
      codon sequence in mRNA and enables its translation into the appropriate amino
      acid. Accordingly, phylogenetic relationships among tRNA genes are often thought
      to recapitulate the evolution of the genetic code. However, it has been
      demonstrated experimentally that one tRNA gene can be replaced with a copy of
      another carrying a single mutation in its anticodon sequence. In this article, we
      show that such "gene recruitment" has occurred recently and repeatedly in the
      mitochondrial genome of the demosponge Axinella corrugata and appears to be a
      common phenomenon in the evolution of the tRNA multigene family.

PMID- 15734571
TI  - A eukaryotic gene family related to retroelement integrases.
AB  - Proteins encoded by mobile genetic elements occasionally assume cellular roles.
      Telomerase, for example, is a reverse transcriptase that replicates chromosome
      ends, and Rag1 is a transposase that mediates immunoglobulin gene rearrangements.
      In this article, we report cellular genes related to integrases that are not
      associated with a retrovirus or retrotransposon. These integrases are found in
      diverse eukaryotes and are evolving under functional constraint. We propose that
      the cellular integrases have assumed a host role and, like their retroelement
      counterparts, probably function in DNA metabolism.

PMID- 15734572
TI  - Chromosomal organization is shaped by the transcription regulatory network.
AB  - Transcription regulation, a key step in the control of gene expression, has been
      the focus of several large-scale studies; however, little attention has been
      given to its relationship with the chromosomal arrangement of transcription
      units. We studied this relationship systematically in Escherichia coli and
      Saccharomyces cerevisiae using network analysis methods. Our analysis reveals
      links between transcription regulation and chromosomal organization, suggesting
      that in both organisms transcription regulation has shaped the organization of
      transcription units on the chromosome. Differences found between the organisms
      reflect the inherent differences in transcription regulation between prokaryotes
      and eukaryotes.

PMID- 15734574
TI  - Developmental gene amplification: insights into DNA replication and gene
      expression.
AB  - In the formation of a complex organism and the differentiation of specific cell
      types, there are often demands for high levels of particular gene products. These
      demands can be met by increasing transcription or translation, or by decreasing
      the rate of mRNA or protein turnover. Although these are the most common means to
      increase expression levels, there is another mechanism: gene amplification.
      Developmental gene amplification is a DNA replication-based process whereby
      specific genes are replicated above the copy number of surrounding sequences,
      resulting in an increase in the template available for transcription. Recent
      microarray studies in Drosophila melanogaster have identified two additional
      amplicons, suggesting that developmental gene amplification might be more widely
      used than was previously thought. Furthermore, work in both Drosophila and the
      related fly, Sciara coprophila, has yielded insights into the mechanisms,
      regulatory sequences and proteins controlling DNA replication during gene
      amplification, including a link between transcription factors and origin usage.

PMID- 15734573
TI  - A new function for nonsense-mediated mRNA-decay factors.
AB  - mRNAs often contain premature-termination (nonsense) codons as a result of
      mutations and RNA splicing errors. These nonsense codons cause rapid decay of the
      mRNAs that contain them, a phenomenon called nonsense-mediated mRNA decay (NMD).
      This response is thought to be a quality-control mechanism that protects cells
      from truncated dominant-negative proteins. Surprisingly, recent evidence strongly
      suggests that the NMD factors UPF1, UPF2, UPF3B, RNPS1, Y14 and MAGOH also
      promote translation of normal mRNAs in mammalian cells. This, along with an
      earlier discovery that NMD factors appear to dictate efficient translation
      termination, suggests that NMD factors do not merely function in RNA
      surveillance. These findings lead to the interesting question of why NMD factors
      evolved; are they for RNA-quality control or to promote efficient translation
      initiation and termination?

PMID- 15734575
TI  - New vision from Eyes absent: transcription factors as enzymes.
AB  - Post-translational modifications such as phosphorylation provide versatile
      context-specific strategies for modulating transcription factor activity. In the
      prevailing view of this process, modifying enzymes indirectly influence gene
      expression by shuttling to and from the nucleus where they alter the activity of
      their target transcription factors. However, a new paradigm has recently been
      suggested from studies of Eyes absent (EYA), a member of a conserved network of
      transcriptional regulators implicated in the development of numerous tissues and
      organs including the eye, ear, muscle and kidney. These findings indicate that
      EYA operates both as a transcriptional coactivator and as the prototype of a
      novel class of protein tyrosine phosphatases. The regulatory potential of such a
      bifunctional transcription factor is enormous and suggests a new layer of dynamic
      regulation in which transcription factors themselves might provide intrinsic
      enzymatic activities to fine-tune nuclear output.

PMID- 15734576
TI  - The dual nature of homologous recombination in plants.
AB  - Homologous recombination creates covalent linkages between DNA in regions of
      highly similar or identical sequence. Recent results from several laboratories,
      many of them based on forward and reverse genetics in Arabidopsis, give insights
      into the mechanisms of the enzymatic machinery and the involvement of chromatin
      in somatic and meiotic DNA recombination. Also, signaling pathways and
      interconnections between repair pathways are being discovered. In addition,
      recent work shows that biotic and abiotic influences from the environment can
      dramatically affect plant genomes. The resulting changes in the DNA sequence,
      exerted at the level of somatic or meiotic tissue, might contribute to evolution.

PMID- 15734577
TI  - Transcription, apoptosis and p53: catch-22.
AB  - The tumor suppressor p53 is a transcription factor and is activated in response
      to DNA damage or oncogenic transformation through modification of its interaction
      with regulatory proteins. The transcription factor activity of p53 is thought to
      mediate its primary functions of cell-cycle arrest and apoptosis through the gene
      expression it regulates, and evidence to support this interpretation continues to
      accumulate. However, reports of transcription-independent activities of p53,
      especially in the induction of apoptosis, persist. In particular, recent studies
      suggest that cytosolic p53 directly interacts with members of the BCL-2 family of
      apoptosis regulators, thereby triggering mitochondrial outer membrane
      permeabilization and apoptosis. In this article, we examine the possible
      relationships between the transcription-dependent activity of p53 and its
      transcription-independent activity, and we propose ways in which both might
      regulate apoptosis.

PMID- 15734579
TI  - Decomposition in soil microcosms of leaves of the metallophyte Arabidopsis
      halleri: effect of leaf-associated heavy metals on biodegradation.
AB  - More knowledge is needed concerning the disturbance of soil organic matter
      cycling due to heavy metal pollution. The present study deals with the impact of
      heavy metal pollution on litter breakdown. Our aim was to assess whether heavy
      metals initially present in the leaves of the metallophyte Arabidopsis halleri:
      (i) slow down the rate of C mineralization, in relation to metal toxicity towards
      microflora, and/or (ii) increase the amount of organic C resistant to
      biodegradation, in relation to an intrinsic resistance of metallophyte residues
      to biodegradation. We incubated uncontaminated soil samples with either metal
      free or metal-rich plant material. Metal-free material was grown in a greenhouse,
      and metal-rich material was collected in situ. During the 2-month period of
      incubation, we measured evolved CO(2)-C and residual plant C in the coarse
      organic fraction. Our results of CO(2)-C evolution showed a similar
      mineralization from the microcosms amended with highly metal-rich leaves of A.
      halleri and the microcosms amended with the metal-free but otherwise similar
      plant material. Measuring residual plant C in its input size-fraction gave a more
      precise insight. Our results suggest that only the large pool of easily
      decomposable C mineralized similarly from metal-free and from metal-rich plant
      residues. The pool of less decomposable C seemed on the contrary to be
      preferentially preserved in the case of metal-rich material. These results
      support the hypothesis of an annual extra-accumulation in situ of such a slowly
      decomposable fraction of plant residues which could account to some extent for
      the observed accumulation of metallophyte litter on the surface of highly metal
      polluted soils.

PMID- 15734578
TI  - The etiology of Wolf-Hirschhorn syndrome.
AB  - Wolf-Hirschhorn syndrome (WHS) is defined by a collection of core
      characteristics, which include mental retardation, epilepsy, growth delay and
      cranio-facial dysgenesis. The disorder is caused by sub-telomeric deletions in
      the short arm of chromosome 4. The severity of the core characteristics is highly
      variable, and additional problems, including midline fusion defects, occur at
      lower frequency. Only one gene, WHSC1, is deleted in every case. However, recent
      evidence, from patient studies and mouse models, indicates that deletion of WHSC1
      alone is insufficient for full-blown WHS. Instead a model is emerging in which
      deletion of WHSC1 is essential for pathogenesis, but deletion of linked genes
      contributes to both the severity of the core characteristics and the presence of
      the additional syndromic problems. In this article, we outline the progress being
      made in patient studies and in the development of mouse models, and relate the
      implications of this work for a broad group of sub-telomeric deletion syndromes.

PMID- 15734580
TI  - Sub-cellular partitioning of Cd, Cu and Zn in tissues of indigenous unionid
      bivalves living along a metal exposure gradient and links to metal-induced
      effects.
AB  - We studied organ and sub-cellular distributions of several trace metals in a
      freshwater bivalve that has been proposed for use as a metal biomonitor.
      Specimens of Pyganodon grandis were collected from nine lakes located along a Cd,
      Cu and Zn concentration gradient (Rouyn-Noranda area, Quebec). Gills and
      digestive gland were isolated, homogenized and six sub-cellular fractions were
      separated by differential centrifugation and analysed for their Cd, Cu and Zn
      content. Metallothionein was quantified independently. Gill tissues contained
      abundant calcium concretions that accounted for over 60% of the total gill burden
      of each metal. Cadmium and Zn concentrations in this granule fraction reflected
      ambient metal concentrations. Metal concentrations in the digestive gland also
      responded to the metal contamination gradient, but to a lesser extent than the
      gills, reflecting the lower abundance of granules in the digestive gland. Metals
      (Cd, Cu) in this organ were present largely in the "heat-stable proteins"
      fraction, and metal concentrations in this fraction were strongly correlated with
      those of both metallothionein and, to a lesser extent, the "lysosomes+microsomes"
      and "mitochondria" fractions. In both organs, Cd concentrations in the "heat
      denaturable protein" fraction remained low and constant, suggesting reasonably
      effective metal detoxification. Some evidence for oxidative stress was noted in
      the gills but not in the digestive gland. Overall, we conclude that in nature
      metals in P. grandis are bound differently in the gills and in the digestive
      gland and that metal detoxification in the former organ may be less effective
      than in the latter.

PMID- 15734581
TI  - Metal stress consequences on frost hardiness of plants at northern high
      latitudes: a review and hypothesis.
AB  - This paper reviews the potential of trace/heavy metal-induced stress to reduce
      plant frost hardiness at northern high latitudes. The scientific questions are
      first outlined prior to a brief summary of heavy metal tolerance. The concepts of
      plant capacity and survival adaptation were used to formulate a hypothesis,
      according to which heavy metal stress may reduce plant frost hardiness for the
      following reasons: (1) Heavy metals change membrane properties through impaired
      resource acquisition and subsequent diminution of the cryoprotectant pool. (2)
      Heavy metals change membrane properties directly through oxidative stress, i.e.
      an increase of active oxygen species. (3) The involved co-stress may further
      increase oxidative stress. (4) The risk of frost injury increases due to membrane
      alterations. An opposite perspective was also discussed: could metal stress
      result in enhanced plant frost hardiness? This phenomenon could be based on the
      metabolism (i.e. glutathione, polyamines, proline, heat shock proteins)
      underlying a possible general adaptation syndrome of stress (GAS). As a result of
      the review it was suggested that metal-induced stress seems to reduce rather than
      increase plant frost hardiness.

PMID- 15734583
TI  - Octanol-solubility of dissolved and particulate trace metals in contaminated
      rivers: implications for metal reactivity and availability.
AB  - The lipid-like, amphiphilic solvent, n-octanol, has been used to determine a
      hydrophobic fraction of dissolved and particulate trace metals (Al, Cd, Co, Cu,
      Mn, Ni, Pb, Zn) in contaminated rivers. In a sample from the River Clyde,
      southwest Scotland, octanol-solubility was detected for all dissolved metals
      except Co, with conditional octanol-water partition coefficients, D(ow), ranging
      from about 0.2 (Al and Cu) to 1.25 (Pb). In a sample taken from the River Mersey,
      northwest England, octanol-solubility was detected for dissolved Al and Pb, but
      only after sample aliquots had been spiked with individual ionic metal standards
      and equilibrated. Spiking of the River Clyde sample revealed competition among
      different metals for hydrophobic ligands. Metal displacement from hydrophobic
      complexes was generally most significant following the addition of ionic Al or
      Pb, although the addition of either of these metals had little effect on the
      octanol-solubility of the other. In both river water samples hydrophobic metals
      were detected on the suspended particles retained by filtration following their
      extraction in n-octanol. In general, particulate Cu and Zn (up to 40%) were most
      available, and Al, Co and Pb most resistant (<1%) to octanol extraction.
      Distribution coefficients defining the concentration ratio of octanol-soluble
      particle-bound metal to octanol-soluble dissolved metal were in the range 10(3.3)
      10(5.3)mlg(-1). The presence of hydrophobic dissolved and particulate metal
      species has implications for our understanding of the biogeochemical behaviour of
      metals in aquatic environments. Specifically, such species are predicted to
      exhibit characteristics of non-polar organic contaminants, including the
      potential to penetrate the lipid bilayer. Current strategies for assessing the
      bioavailability and toxicity of dissolved and particulate trace metals in natural
      waters may, therefore, require revision.

PMID- 15734582
TI  - Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in
      tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan.
AB  - A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models were
      developed for arsenic (As) in tilapia Oreochromis mossambicus from blackfoot
      disease area in Taiwan. The PBPK/PD model structure consisted of muscle, gill,
      gut wall, alimentary canal, and liver, which were interconnected by blood
      circulation. We integrate the target organ concentrations and dynamic response
      describing uptake, metabolism, and disposition of As and the associated area
      under-curve (AUC)-based toxicological dynamics following an acute exposure. The
      model validations were compared against the field observations from real tilapia
      farms and previously published uptake/depuration experimental data, indicating
      that predicted and measured As concentrations in major organs of tilapia were in
      good agreement. The model was utilized to reasonably simulate and construct a
      dose-dependent dynamic response between mortality effect and equilibrium target
      organ concentrations. Model simulations suggest that tilapia gills may serve as a
      surrogate sensitive biomarker of short-term exposure to As. This integrated As
      PBPK/PD/AUC model quantitatively estimates target organ concentration and dynamic
      response in tilapia and is a strong framework for future waterborne metal model
      development and for refining a biologically-based risk assessment for exposure of
      aquatic species to waterborne metals under a variety of scenarios.

PMID- 15734584
TI  - Dietary mercury exposure and bioaccumulation in amphibian larvae inhabiting
      Carolina bay wetlands.
AB  - Inorganic mercury and methylmercury concentrations were measured both in guts and
      remaining carcasses of southern leopard frog (Rana sphenocephala) larvae from 10
      Carolina bay wetlands in South Carolina, USA. Significant variation among bays in
      methylmercury and inorganic mercury concentrations existed both in guts and
      carcasses. There was a moderate negative correlation between dissolved organic
      carbon concentration in bays and mean inorganic mercury concentrations in guts.
      There was also a weak positive correlation between pH in bays and mean
      methylmercury concentrations in carcasses. The ratio of methylmercury to
      inorganic mercury decreased with increasing total mercury concentration in guts
      and in larvae, but the rate of decrease was highly variable among bays. Ratios of
      concentrations in carcasses to concentrations in guts were inversely related to
      gut concentration. Mercury concentrations in carcasses in some bays were within
      the range of concentrations at which adverse effects have been observed in
      laboratory studies of R. sphenocephala.

PMID- 15734586
TI  - In vitro toxicity of selected pesticides on RTG-2 and RTL-W1 fish cell lines.
AB  - The rainbow trout fish cell lines RTG-2 and RTL-W1 were used to determine the
      cytotoxic effects of the pesticides bifenthrin, cypermethrin, cyhalothrin, lambda
      cyhalothrin, quinalphos and chlorpyrifos. Cytotoxicity was measured by EROD and
      beta-Gal enzymatic activities, the neutral red (NR) uptake assay, and the FRAME
      KB protein (KBP) assay. The beta-Gal activity was unaffected by the pesticide
      exposure. The EROD activity was induced by cyhalothrin and lambda-cyhalothrin
      (RTG-2 and RTL-W1) and by bifenthrin (RTL-W1). Dose dependent inhibition
      responses were observed for EROD activity in cells exposed to quinalphos (RTL-W1)
      and chlorpyrifos (RTG-2 and RTL-W1). RTL-W1 offered a better response for EROD
      induction. The EC50 values on EROD endpoint were more sensitive than NR and KBP.
      The acute fish toxicity of chlorpyrifos and quinalphos depends highly on the
      species; the species sensitivity distributions cover several orders of magnitude
      and the values obtained for EROS were within the lowest part of the reported
      ranges.

PMID- 15734585
TI  - Diversity of arbuscular mycorrhizal fungi in grassland spontaneously developed on
      area polluted by a fertilizer plant.
AB  - Mycorrhizal colonization and diversity of arbuscular mycorrhizal fungi (AMF) were
      analyzed in a calcareous grassland with residual phosphate contamination 10 years
      after the closure of a pollutant fertilizer plant in Thuringia (Germany). AMF
      were detected in 21 of 22 plant species analyzed. Mean mycorrhization levels
      reached up to 74.5% root length colonized. AMF diversity was analyzed based on
      104 sequences of the internal transcribed spacer (ITS) of the ribosomal DNA.
      Phylogenetic analyses revealed a total of 6 species all belonging to the genus
      Glomus. There was no overlap between species detected as active mycorrhizas on
      roots (2 taxa) or as spores (4 taxa). Compared to the regional context, the
      diversity of AMF at our field site was reduced, which may reflect a residual
      disturbance effect. However, none of the detected species was exclusive to the
      polluted site as they are commonly found in the region.

PMID- 15734587
TI  - Early-phase immunodetection of metallothionein and heat shock proteins in
      extruded earthworm coelomocytes after dermal exposure to metal ions.
AB  - This paper provides direct evidence that earthworm immune cells, coelomocytes,
      are exposed to bio-reactive quantities of metals within 3 days after dermal
      exposure, and that they respond by upregulating metallothionein (MT) and heat
      shock protein (HSP70, HSP72) expression. Indirect support for the hypothesis that
      coelomocytes are capable of trafficking metals was also obtained. Coelomocytes
      were expelled from adult individuals of Eisenia fetida after 3-day exposure
      either to metal ions (Zn, Cu, Pb, Cd) or to distilled water (controls) via filter
      papers. The number of coelomocytes was significantly decreased after Cu, Pb, or
      Cd treatment. Cytospin preparations of coelomocytes were subjected to
      immunoperoxidase staining with monoclonal antibodies against human heat shock
      proteins (HSP70 or HSP72), or rabbit polyclonal antibodies raised against
      metallothionein 2 (w-MT2) of Lumbricus rubellus. Applied antibodies detected the
      respective proteins of E. fetida and revealed that the expression of HSP70, HSP72
      and w-MT2 proteins was either induced or significantly enhanced in coelomocytes
      from metal-exposed animals. In conclusion, stress protein expression in earthworm
      coelomocytes may be used as sensitive biomarkers of metal contaminations. Further
      experimentation is needed for quantitative analysis of kinetics of metal-induced
      stress protein expression in earthworm coelomocytes.

PMID- 15734588
TI  - Oxygen levels versus chemical pollutants: do they have similar influence on
      macrofaunal assemblages? A case study in a harbour with two opposing entrances.
AB  - Generally, harbours are polluted zones characterised by low values of
      hydrodynamism and oxygen in the water column and high concentrations of
      pollutants in sediments. The harbour of Ceuta, North Africa, has an unusual
      structure; it is located between two bays connected by a channel, which increases
      the water movement and exchange in the harbour, maintaining moderate oxygen
      levels in the water-sediment interface. Nevertheless, high concentration of
      organic matter, nutrients and heavy metals were measured in sediments from this
      harbour. Under these unusual conditions (high levels of pollution but total
      saturation of oxygen in the water column) we studied the responses of soft-bottom
      macrobenthic communities using uni and multivariate analyses. The number of
      species was similar inside and outside the harbour but the species composition
      differed between internal and external stations; oxygen levels seem to control
      the "quantity" of species whereas pollutants control the "quality" of them.

PMID- 15734589
TI  - The Solling roof revisited--slow recovery from acidification observed and modeled
      despite a decade of "clean-rain" treatment.
AB  - Soil chemistry under the Solling clean-rain roof was simulated using the dynamic
      multi-layer soil chemistry model SAFE, including sulfate adsorption. Soil was
      sampled in order to parameterize the pH and sulfate concentration dependent
      sulfate adsorption isotherm used in SAFE. Modeled soil solution chemistry was
      compared to the 14 year long time-series of monthly measurements of soil solution
      data at 10 and 100cm depth. The deposition of N and S under the roof has been
      reduced by 68% and 53%, respectively, compared to the surrounding area. Despite
      this the soil solution concentrations of sulfate are still high (a median of
      420mumol(c)/L at 100cm depth between 2000 and 2002) and the soil base saturation
      low (approximately 3% in the whole profile in 1998). Sulfate adsorption is an
      important process in Solling. The soil capacity to adsorb sulfate is large, the
      modeled adsorbed pool in 2003 down to 100cm was 1030kg S/ha, and the measured
      sulfate concentration is high, due to release of adsorbed sulfate. The addition
      of sulfate adsorption improved the modeled sulfate dynamics although the model
      still slightly underestimated the sulfate concentration at 100cm. Model
      predictions show no recovery, based on the criteria of Bc/Al ratio above 1 in the
      rooting zone, before the year 2050, independent of future deposition cuts.

PMID- 15734590
TI  - The effect of hydrological regime on the metal bioavailability for the wetland
      plant species Salix cinerea.
AB  - The hydrological conditions on a site constitute one of the many factors that may
      affect the availability of potentially toxic trace metals for uptake by plants.
      Bioavailability of Cd, Mn and Zn in a contaminated dredged sediment-derived soil
      under different hydrological regimes was determined by measuring metal uptake by
      the wetland plant species Salix cinerea, both in field circumstances and in a
      greenhouse experiment. Longer submersion periods in the field caused lower Cd
      concentrations in leaves and bark. The wetland hydrological regime in the
      greenhouse experiment resulted in normal Cd and Zn concentrations in the leaves,
      while the upland hydrological regime resulted in elevated Cd and Zn
      concentrations in the leaves. Field observations and the greenhouse experiment
      suggest that a hydrological regime that creates or sustains a wetland is a
      potential management option that reduces metal bioavailability to willows. This
      would constitute a safe management option of metal-polluted, willow-dominated
      wetlands provided that wetland conditions can be maintained throughout the full
      growing season.

PMID- 15734591
TI  - Manganese toxicity thresholds for restoration grass species.
AB  - Manganese toxicity thresholds for restoration plants have not been established.
      As a result, ecological risk assessments rely on toxicity thresholds for
      agronomic species, which may differ from those of restoration species. Our
      objective was to provide Mn toxicity thresholds for grasses commonly used in
      restoration. We used a greenhouse screening study where seedlings of redtop,
      slender wheatgrass, tufted hairgrass, big bluegrass, basin wildrye, and common
      wheat were grown in sand culture and exposed to increasing concentrations of Mn.
      The LC50, EC50-plant, EC50-shoot, EC50-root, PT50-shoot, and the PT50-root were
      then determined. Phytotoxicity thresholds and effective concentrations for the
      restoration species were generally higher than values reported for agronomic
      species. Our estimates of PT50-shoot for the five restoration grasses range from
      41,528 to 120,082 mg Mn kg(-1). Measures of EC50-plant for these restoration
      grasses ranged from 877 to >6,000 mg Mn l(-1). These thresholds might be more
      useful for risk assessors than those based on crop plants that are widely used.

PMID- 15734592
TI  - Decomposition of leaves of the metallophyte Arabidopsis halleri in soil
      microcosms: fate of Zn and Cd from plant residues.
AB  - In order to better understand the fate of metals during the biodegradation of
      organic matter in soils, an in vitro incubation experiment was conducted with
      metal-rich and metal-free leaves of Arabidopsis halleri introduced in a non
      contaminated soil. During incubation of these microcosms, we followed the
      partitioning of Zn and Cd between the solution and their solid components, by
      determining the metal contents of six soil fractions and dissolved metals after
      granulo-densimetric separations at selected times. Microbial biomass and
      exchangeable metals in K(2)SO(4) solutions were also determined at the same
      times, and two main stages were identified. The first one takes place after a
      fast abiotic transfer of Zn and Cd from readily soluble plant tissues onto fine
      soil constituents, keeping metals away from the liquid phase: during about 14
      days, microbial biomass increased as well as metal contents of some soil
      fractions, particularly those rich in particulate organic matter. During the
      second stage, between 14 and 60 days and for the metal-rich microcosms, Zn and Cd
      contents in solution increased, while microbial biomass decreased instead of
      staying constant as in control. A change of Zn and Cd speciation is assumed, from
      non-toxic adsorbed forms to more toxic species in solution. Remaining metal-rich
      plant residues seem to create a stable organic C compartment in the soil.

PMID- 15734593
TI  - Effects of arsenic on concentration and distribution of nutrients in the fronds
      of the arsenic hyperaccumulator Pteris vittata L.
AB  - Pteris vittata was the first terrestrial plant known to hyperaccumulate arsenic
      (As). However, it is unclear how As hyperaccumulation influences nutrient uptake
      by this plant. P. vittata fern was grown in soil spiked with 0-500 mg As kg(-1)
      in the greenhouse for 24 weeks. The concentrations of essential macro- (P, K, Ca,
      and Mg) and micro- (Fe, Mn, Cu, Zn, B and Mo) elements in the fronds of different
      age were examined. Both macro- and micronutrients in the fronds were found to be
      within the normal concentration ranges for non-hyperaccumulators. However, As
      hyperaccumulation did influence the elemental distribution among fronds of
      different age of P. vittata. Arsenic-induced P and K enhancements in the fronds
      contributed to the As-induced growth stimulation at low As levels. The frond P/As
      molar ratios of 1.0 can be used as the threshold value for normal growth of P.
      vittata. Potassium may function as a counter-cation for As in the fronds as shown
      by the As-induced K increases in the fronds. The present findings not only
      demonstrate that P. vittata has the ability to maintain adequate concentrations
      of essential nutrients while hyperaccumulating As from the soil, but also have
      implications for soil management (fertilization in particular) of P. vittata in
      As phytoextraction practice.

PMID- 15734594
TI  - Comment on "Characterization of a reference site for quantifying uncertainties
      related to soil sampling" by S. Barbizzi et al (2004).

PMID- 15734595
TI  - A TA-repeat polymorphism in the gene for the estrogen receptor alpha does not
      correlate with muscle strength or body composition in young adult Swedish women.
AB  - OBJECTIVES: There are conflicting data in the literature whether estrogens affect
      muscle strength. Prospective studies with hormone replacement therapy have not
      been able to convincingly demonstrate a muscular effect and the putative role of
      estrogen in the development of lean body mass is not established. Both lean mass
      and fat mass are known to be under strong genetic control and therefore we have
      investigated the relation between a TA-repeat in the gene for the estrogen
      receptor alpha (ERalpha) and muscle strength and body composition. METHODS: 175
      healthy Swedish women, aged 20-39 were randomly selected from the population
      registry and included in the study. Body mass measurements (lean mass, fat mass,
      body weight and BMI) and muscle strength (quadriceps, hamstring and grip
      strength) were evaluated. The TA-repeat in the ERalpha gene was amplified by
      polymerase chain reaction. RESULTS: Alleles with a TA-repeat length of 16 repeats
      or shorter were denoted short (e), and repeat length of 17 repeats or longer were
      denoted long (E). Women homozygous for the short and long genotype were denoted
      ee (31%) and EE (21%), respectively, while heterozygous individuals were denoted
      Ee (48%). The frequencies were in Hardy-Weinberg equilibrium. No associations
      were found between ERalpha genotypes and muscle strength or body composition.
      CONCLUSION: The TA-repeat in the human ERalpha gene does not correlate with
      muscle strength or body mass measurements, indicating that body composition is
      not as sensitive to genetic variation in this receptor as other target organs for
      estrogen.

PMID- 15734596
TI  - Prevalence of symptoms possibly related to PADAM, in a Swedish population aged
      55, 65 and 75 years.
AB  - OBJECTIVES: With age there is an average decline in the concentration of
      biologically active testosterone. It is still controversial if this leads to a
      clinically relevant deficit, "partial androgen deficiency of the ageing man"
      (PADAM). Our objective was to investigate the prevalence of a series of symptoms
      possibly associated with PADAM in an assumed normal-population of older men.
      METHODS: We developed a questionnaire including items about symptoms possibly
      associated with PADAM as well as background data covering demography, medical
      history, mood status, medication, castration therapy, as well as smoking,
      exercise and alcohol habits. The 10 items of the ADAM-questionnaire, designed to
      predict low bio-available T, were also included. The questionnaire was sent to
      all 1885 men 55, 65 or 75-years-old, living in Linkoping, Sweden. RESULTS: We
      identified a number of symptoms that differed significantly (P < 0.01) between
      age groups, e.g., "increased abdominal circumference", "decrease in muscle
      strength and/or endurance", "decreased libido", "less strong erection" and "lack
      of energy". From factorial analysis we found that the symptoms co-varied in four
      different groups. CONCLUSION: The prevalence of a number of symptoms differed
      significantly between age groups, but we cannot infer that there is a causal
      connection between an average age-dependent decline in testosterone function and
      these symptoms. There are several other ways to interpret these results like the
      existence of concurrent somatic and/or mood disorders or ageing as such. For this
      purpose further studies including measurements of testosterone concentrations
      relating to the findings of this study have to be performed.

PMID- 15734597
TI  - Women with and without menopause over age of 40 in Turkey: consequences and
      treatment options.
AB  - AIM: To investigate the characteristics of menopausal population who gets free
      first step health-care services from government facilities in the Central
      Anatolia Region of Turkey. METHODS: One thousand and forty-nine pre- (N = 403)
      and post (N = 646)-menopausal females were interviewed with a questionnaire in
      five different facilities during 2 weeks. RESULTS: The group, who never used oral
      contraceptive as a family planning method, never smoked and had a low rate of
      illiteracy (72.5, 72.5, 77.7, and 12.1%, respectively. Mean age of the menopause
      was 45.8 +/- 5.5 years. Mean years since menopause was 13.2 +/- 9.6 years and
      mode of the menopause was 10 years. Group of postmenopausal women knew the
      meaning of menopause as "ceasing of menses" in a significantly higher rate
      compared to pre-menopausal group (6.9% versus 2.2%, respectively). While rate of
      the women regularly visiting free health-care facilities and rate of receiving
      some form of HRT is observed to be relatively low (33 and 29.4%, respectively),
      no significant differences were observed in symptoms rating between pre- and post
      menopausal group restlessness, uneasy feeling, insomnia, flushing, sweating,
      tachycardia, short memory, bone and muscle pain, and nocturia and therefore such
      symptoms seem to be unrelated to their menopausal status. CONCLUSIONS: Women are
      entering to menopause earlier and using the free medical facilities in this
      region of Turkey less, compared to European population and seeking less help for
      menopause during this period. They are mostly married, with lower preferences for
      oral medications, non-smokers, relatively literate group of people; however, with
      low awareness of their current situation regarding the phenomenon of "ceasing of
      menses" and its consequences.

PMID- 15734598
TI  - Differential indication for histological evaluation of endometrial fluid in
      postmenopause.
AB  - OBJECTIVES: The endometrium carcinoma is the most frequent malignancy of the
      female genital tract. Approximately, 10-20% of all patients with an endometrial
      carcinoma are free of symptoms until the time of diagnosis. The frequent
      occurrence of an endometrial carcinoma in connection with intrauterine cavity
      fluid collection (sero- or mucometra) has been discussed controversially in
      literature. What are the hysteroscopic and histological findings in patients with
      sonographically determined endometrial fluid in postmenopause, and how should
      these findings be interpreted? METHODS: 74 patients, in whom endometrial fluid
      without bleeding disorders had been diagnosed during routine transvaginal
      sonography, underwent hysteroscopy conducted with a 4.5 mm optics and dilatation
      and curettage (D&C). The median age of the patients was 68 years with a range of
      32 years. RESULTS: The simple thickness of the endometrium, i.e. single layer
      measured sonographically at the point of maximal thickness, was on average 5.7 mm
      +/- 3.6 mm (2-15 mm). Hysteroscopically, an endometrium polyp was found in 23
      cases (31.1%), endometrium hyperplasia in 12 (16.2%), and an atrophy in 35 cases
      (47.3%). In four cases (5.4%), an endometrial carcinoma was suspected. The
      histological results were consistent with the hysteroscopic findings. In all
      instances, in which the simple endometrial thickness amounted to 3 mm or less, an
      atrophic endometrium was found. The frequency of intrauterine pathologies
      increased significantly with a greater thickness of the endometrium. In 80% of
      patients, a cervical stenosis existed. CONCLUSIONS: Endometrial fluid by itself,
      without assessment of the endometrium, does not indicate the requirement for
      additional histological clarification. As diagnostics, the authors suggest
      especially the endometrial morphology.

PMID- 15734599
TI  - Effects of raloxifene on serum malondialdehyde, erythrocyte superoxide dismutase,
      and erythrocyte glutathione peroxidase levels in healthy postmenopausal women.
AB  - OBJECTIVE: To investigate the relationship between raloxifene administration and
      serum malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), erythrocyte
      glutathione peroxidase (GPx) levels in healthy postmenopausal women. METHODS: In
      a randomized and placebo-controlled design, 80 women received either 60 mg/day
      raloxifene or placebo for 24 weeks. MDA, SOD, and GPx levels were assessed at
      0,4,12, and 24 weeks. Wilcoxon signed-rank test and Mann-Whitney U test were used
      for comparisons. RESULTS: Six women in the treatment arm and eight women in the
      placebo group discontinued the study. Mean serum MDA levels were significantly (p
      = 0.001) decreased from 11.4 nmol/ml at baseline to 8.9 nmol/ml at week 12 with
      raloxifene treatment. Mean erythrocyte SOD activity was significantly (p = 0.02)
      reduced from 1472 U/g Hb at baseline to 1173 U/g Hb at week 12 following
      raloxifene administration. Lowered serum MDA and erythrocyte SOD levels persisted
      during treatment. On contrary, erythrocyte GPx levels did not change
      significantly with raloxifene administration. CONCLUSIONS: Raloxifene (60 mg/day)
      lowers serum MDA levels and erythrocyte SOD activity in postmenopausal women
      after 12 weeks of treatment. The clinical implications of these findings need to
      be determined.

PMID- 15734600
TI  - The impact of a monophasic continuous estro-progestogenic treatment on Latin
      American menopausal women.
AB  - OBJECTIVE: The present study was undertaken to assess the impact, effectiveness
      and safety of a monophasic hormone replacement treatment (HRT) for continuous use
      with regards to the clinical effects, bleeding patterns and lipid profile of
      menopausal women in four Latin American countries. DESIGN: Three hundred and six
      postmenopausal women with natural menopause and uterus present were recruited.
      This was a multicentre prospective, clinical trial; the participating countries
      were Brazil (BR), Colombia (CO), Mexico (MX) and Argentina (AR). The study period
      was 12 months. The HRT regime was formulated in tablets containing 2 mg estradiol
      E2 and 1mg norethisterone acetate (NETA); one visit every 3 months was solicited.
      METHODS: HRT was given as one tablet every day without interruption for 1 year.
      Climacteric complaints, side-effects, reason for discontinuation, bleeding
      patterns, lipid profile at baseline and 12 months of treatment were documented.
      RESULTS: There were no significant differences between the four populations on
      clinical measurements. Thirty-four women discontinued, 13 for bleeding problems.
      The five most common side-effects were mastalgia, bleeding problems, headache,
      pelvic pain and nausea. 44.8% of women experienced scanty vaginal bleeding during
      the first 3 months of therapy. Ninety seven percent of women had amenorrhea at
      the end of the study in MX, BR and AR, and 100% in CO. Body weight was constant
      during the study, and no correlation was found between body weight and total days
      with bleeding. The Kupperman index score was used to evaluate the climacteric
      complaints, and the score decreased from a mean of 25.4 to 5.1 at 12-months
      visit. Total cholesterol levels were significantly reduced in BR and CO (P <
      0.05) between baseline and the final sample; serum triglycerides remained
      unchanged, HDL-cholesterol was significantly increased in MX (P < 0.05), and LDL
      cholesterol was significantly reduced in CO (P < 0.05). The results of this 1
      year study emphasize that a continuous combined HRT regimen with 2 mg E2/1 mg
      NETA is an attractive alternative for postmenopausal women who are at least 1
      year after their menopause and optimally 2 years after their menopause. Although
      the combination of 2 mg E2 with 1 mg NETA in a continuous combined therapy scheme
      has been in use in the Nordic countries for over a decade and in Latin America
      for the last 6 years, there have been no previous published reports on its
      effectivity in Latin American women. This publication reports the experience in a
      group of 306 Latin American women, and it is the first Latin American publication
      with this formulation.

PMID- 15734601
TI  - Osteoporosis beliefs and antiresorptive medication use.
AB  - OBJECTIVE: Although a number of prescription medications are effective for the
      prevention and treatment of osteoporosis, little is known about the role of
      beliefs and attitudes in women decisions to use these drugs. The objectives of
      this study were (1) to assess the role of beliefs and attitudes regarding
      osteoporosis and prescription antiresorptive drugs in the decision to use newer
      antiresorptive medicines (such as bis-phosphonates, selective estrogen receptor
      modulators, and calcitonin nasal) and (2) to assess the role of these same
      beliefs and attitudes in the decision to use hormone therapy. DESIGN: Data were
      collected using a cross-sectional survey mailed to 1700 community dwelling women
      age 45 and older residing in Minnesota. Respondents completed measures of health
      belief model constructs, medication profiles and demographics. Data were analyzed
      using multivariate logistic regression models. RESULTS: A total of 983 usable
      survey forms were returned, yielding an adjusted response rate of 60.7%. More
      than one quarter of respondents reported using a prescription antiresorptive
      agent, with 90 (9.2%) currently taking a newer antiresorptive agent and 163
      (16.6%) using hormone therapy. Several health belief model components were
      predictive of newer antiresorptive medicine use, including higher perceptions of
      susceptibility to osteoporosis (OR 1.34, 95% CI 1.20-1.49), perceptions of strong
      benefits of antiresorptive medicines (OR 1.34, 95% CI 1.10-1.63), and perceptions
      of few barriers to the use of antiresorptive medicines (OR 0.51, 95% CI 0.38
      0.67). Several cues to action also were predictive of newer antiresorptive
      medicine use. Use of hormone therapy was associated with a single cue to action
      (being tested for osteoporosis (OR 1.74, 95% CI 1.14-2.66) and the perception of
      few barriers to the use of prescription antiresorptives (OR 0.65, 95% CI 0.55
      0.77). CONCLUSION: Several health belief model constructs were associated with
      the decision to use newer antiresorptive drugs relative to no prescription
      therapy. However, few model components as operationalized in this study were
      predictive of the use of hormone therapy. Although the health belief model
      appears to provide a plausible model of the decision to undertake newer
      antiresorptive drug therapy, it explains little about women use of hormone
      therapy.

PMID- 15734602
TI  - Further psychometric property development of the Menopause-Specific Quality of
      Life questionnaire and development of a modified version, MENQOL-Intervention
      questionnaire.
AB  - OBJECTIVES: To develop the 1996 MENQOL questionnaire further with advice
      regarding summary score computation, missing-data management, readability, recall
      period and assessment of the vasomotor domain reliability and construct validity.
      To develop a modified version, the MENQOL-Intervention questionnaire, for use
      where certain treatment side effects could negatively impact the quality of life.
      METHODS: MENQOL-Intervention modifications involved the addition of three items
      to the physical domain. For both questionnaires, psychometric property assessment
      was embedded in two randomized controlled trials of menopause interventions. Test
      retest reliability and Cronbach's alpha were computed for all domains as was
      construct validity of the vasomotor domain for both questionnaires. RESULTS: The
      vasomotor intraclass correlation coefficient was 0.73 for the MENQOL-Intervention
      over 1 week and 0.78 for the MENQOL over 1 month. The altered physical domain of
      the MENQOL-Intervention questionnaire continued to show strong test-retest
      reliability and Cronbach's alpha consistent with the MENQOL. The MENQOL
      Intervention demonstrated excellent face validity with high construct validity
      for the vasomotor domain of 0.78-0.80. For both instruments, comparisons of the
      vasomotor domains to hot flash scores, although statistically significant, were
      only moderate at 0.56 and 0.49. CONCLUSIONS: Both the MENQOL and the MENQOL
      Intervention questionnaires show strong psychometric properties. We recommend
      using the MENQOL-Intervention questionnaire where intervention side effects might
      negatively impact a woman's quality of life. For both questionnaires, a summary
      score can be calculated.

PMID- 15734603
TI  - Tibolone relieves climacteric symptoms in highly symptomatic women with at least
      seven hot flushes and sweats per day.
AB  - OBJECTIVE: To establish the potency of four dose levels of tibolone, a tissue
      selective estrogenic activity regulator (STEAR), to relieve climacteric symptoms
      in a subgroup of highly symptomatic women experiencing a minimum of seven hot
      flushes and sweats per day. METHODS: In a group of 770 women receiving tibolone
      0.625, 1.25, 2.5 or 5.0 mg or placebo for 12 weeks, a total of 317 women
      experienced at least seven hot flushes and sweats per day. Frequency and
      intensity of climacteric symptoms were assessed at baseline and after 4, 8 and 12
      weeks of treatment. Vaginal bleeding/spotting was studied using diary cards.
      Occurrence of adverse events was determined by active questioning. RESULTS:
      Tibolone induced a decrease in the frequency and intensity of climacteric
      symptoms, leading to statistically significant differences compared to placebo
      for dose levels of 1.25 mg and higher. The incidence of vaginal bleeding/spotting
      and of drug-related adverse events was similar in all tibolone dose groups,
      except for the 5.0 mg group, where the incidence was about twice as high. Dropout
      rate due to insufficient therapeutic effect is substantially higher in the 0.625
      and 1.25 mg group (about 10%) compared to the 2.5 and 5.0 mg group (about 1%).
      These results are consistent with what occurred in the total study population
      published previously. CONCLUSION: The effects of tibolone in highly symptomatic
      women experiencing at least seven hot flushes and sweats per day do not differ
      much from that in the total study population. A daily dose of 2.5 mg is the
      optimal dose for both the total study population and the subgroup of highly
      symptomatic women. However, in order to optimise individual treatment, the 1.25
      mg dose might also be taken into consideration.

PMID- 15734604
TI  - The role of hormone replacement therapy in endometrial polyp formation.
AB  - OBJECTIVE: To evaluate the iatrogenic effect of different protocols of hormone
      replacement therapy (HRT) on endometrial polyp formation adjusting for the
      confounding effects of other factors such as age, parity, weight and menopausal
      status at menopause. METHODS: Out of 2685 menopause patients 375 (13.9%) eligible
      patients were enrolled. Patients were randomized to three HRT types and three
      equal groups were formed. The first group received Premelle 2.5 mg (Group-I)
      (0.625 mg conjugated estrogen + 2.5 mg medroxyprogestorone), the second received
      Kliogest (Group-II) (2 mg estradiol + 1 mg norethisterone) and the last received
      Livial (Group-III) (2.5 mg tibolone) at least for 36 months without giving a
      break. After the first 18 months patients had their first office hysteroscopy and
      it was repeated in every 6 months until the end of third year to find out new and
      recurrent endometrial polyps. RESULTS: Multiple regression analysis revealed that
      the type of HRT, late menopause and obesity increased the occurrence of
      endometrial polyps. In Group-I five polyps, in Group-II ten polyps and in Group
      III two polyps were detected. There were significant differences between G-II and
      G-I and G-II and G-III (P < 0.05), but there was no significant difference
      between G-I and G-III (P > 0.05). 82.3% of the polyps were detected in the third
      and fourth hysteroscopic examinations. Endometrial polyp recurrence was
      encountered in 4 (23.5%) patients, 1 in G-I and 3 in G-II without a significant
      difference (P > 0.05). No malignancy was detected in any of the specimen.
      CONCLUSION: We observed that endometrial polyp formation may be dependent on the
      type and dosage of the estrogen and progestogen. Especially a progestogen with
      high antiestrogenic activity may play an important preventive role in the
      development of endometrial polyps.

PMID- 15734605
TI  - The epidemiology, pathophysiology, and management of psychosocial risk factors in
      cardiac practice: the emerging field of behavioral cardiology.
AB  - Observational studies indicate that psychologic factors strongly influence the
      course of coronary artery disease (CAD). In this review, we examine new
      epidemiologic evidence for the association between psychosocial risk factors and
      CAD, identify pathologic mechanisms that may be responsible for this association,
      and describe a paradigm for studying positive psychologic factors that may act as
      a buffer. Because psychosocial risk factors are highly prevalent and are
      associated with unhealthy lifestyles, we describe the potential role of
      cardiologists in managing such factors. Management approaches include routinely
      screening for psychosocial risk factors, referring patients with severe
      psychologic distress to behavioral specialists, and directly treating patients
      with milder forms of psychologic distress with brief targeted interventions. A
      number of behavioral interventions have been evaluated for their ability to
      reduce adverse cardiac events among patients presenting with psychosocial risk
      factors. Although the efficacy of stand-alone psychosocial interventions remains
      unclear, both exercise and multifactorial cardiac rehabilitation with
      psychosocial interventions have demonstrated a reduction in cardiac events.
      Furthermore, recent data suggest that psychopharmacologic interventions may also
      be effective. Despite these promising findings, clinical practice guidelines for
      managing psychosocial risk factors in cardiac practice are lacking. Thus, we
      review new approaches to improve the delivery of behavioral services and patient
      adherence to behavioral recommendations. These efforts are part of an emerging
      field of behavioral cardiology, which is based on the understanding that
      psychosocial and behavioral risk factors for CAD are not only highly
      interrelated, but also require a sophisticated health care delivery system to
      optimize their effectiveness.

PMID- 15734606
TI  - Angioscopic follow-up study of coronary ruptured plaques in nonculprit lesions.
AB  - OBJECTIVES: Changes of ruptured plaques in nonculprit lesions were evaluated
      using coronary angioscopy. BACKGROUND: The concept of multiple coronary plaque
      ruptures has been established. However, no detailed follow-up studies of ruptured
      plaques in nonculprit lesions have yet been reported. METHODS: Forty-eight
      thrombi in 50 ruptured coronary plaques in nonculprit lesions in 30 patients were
      identified by angioscopy. The percent diameter stenosis (%DS) at the target
      plaques on quantitative coronary angiographic analysis and the serum C-reactive
      protein (CRP) level were measured. RESULTS: The mean angioscopic follow-up period
      was 13 +/- 9 months. Thirty-five superimposed thrombi still remained at follow
      up, and the predominant thrombus color changed from red (56%) at baseline to
      pinkish-white (83%) at follow-up. The healing rate increased according to the
      angioscopic follow-up period (23% at </=12 months vs. 55% at >12 months, p =
      0.044). The %DS at the healed plaque increased from baseline to follow-up (12.3
      +/- 5.8% vs. 22.7 +/- 11.6%, respectively; p = 0.0004). The serum CRP level in
      patients with healed plaques (n = 10) was lower than that in those without healed
      plaques (n = 19; 0.07 +/- 0.03 mg/dl vs. 0.15 +/- 0.11 mg/dl, respectively; p =
      0.007). CONCLUSIONS: The present study demonstrated that: 1) ruptured plaques in
      nonculprit lesions tend to heal slowly with a progression of angiographic
      stenosis; and 2) the serum CRP level might reflect the disease activity of the
      plaque ruptures.

PMID- 15734607
TI  - Plaque rupture and intracoronary thrombus in nonculprit vessels: an eyewitness
      account.

PMID- 15734608
TI  - Effects of candesartan on cardiac sympathetic nerve activity in patients with
      congestive heart failure and preserved left ventricular ejection fraction.
AB  - OBJECTIVES: We sought to evaluate the effects of angiotensin receptor blocker
      (ARB) on cardiac sympathetic nerve activity (CSNA) in patients with congestive
      heart failure (CHF) with a preserved left ventricular ejection fraction (LVEF).
      BACKGROUND: Approximately 50% of patients with CHF have preserved LVEF. It is
      reported that ARB therapy improves CSNA in CHF patients and reduced LVEF.
      However, the effect of ARB therapy on CSNA evaluated by iodine-123 meta
      iodobenzylguanidine ((123)I-MIBG) scintigraphy has not been determined in CHF
      patients with preserved LVEF. METHODS: We selected 50 patients with nonischemic
      CHF and LVEF >40% who were treated with standard therapy. Twenty-five patients
      were randomized to also receive candesartan, whereas the remaining 25 patients
      received placebo. The delayed heart/mediastinum count (H/M) ratio, delayed total
      defect score (TDS), and washout rate (WR) were determined by (123)I-MIBG
      scintigraphy before and six months after treatment. The LV end-diastolic volume
      and LVEF were determined by echocardiography, and the plasma brain natriuretic
      peptide (BNP) concentration was also measured. RESULTS: In patients receiving
      candesartan, (123)I-MIBG scintigraphic and echocardiographic parameters were
      significantly improved after treatment. In contrast, there were no significant
      changes in these parameters in patients receiving placebo. There was a
      significant correlation between the changes in (123)I-MIBG scintigraphic findings
      and the percent change in BNP from baseline to six months in patients receiving
      candesartan (TDS: r = 0.587, p < 0.005; H/M ratio: r = -0.509, p < 0.01; WR: r =
      0.602, p < 0.005). CONCLUSIONS: Adding candesartan to standard therapy can
      improve CSNA and LV performance in CHF patients with preserved LVEF.

PMID- 15734609
TI  - Left ventricular assist device support normalizes left and right ventricular beta
      adrenergic pathway properties.
AB  - OBJECTIVES: We hypothesized that some aspects of left ventricular assist device
      (LVAD) reverse remodeling could be independent of hemodynamic factors and would
      primarily depend upon normalization of neurohormonal milieu. BACKGROUND: The
      relative contributions of LVAD-induced hemodynamic unloading (provided to the
      left ventricle [LV]) and normalized neurohormonal milieu (provided to LV and
      right ventricle [RV]) to reverse remodeling are not understood. METHODS:
      Structural and functional characteristics were measured from hearts of 65
      medically managed transplant patients (MED), 30 patients supported with an LVAD,
      and 5 nonfailing donor hearts not suitable for transplantation. RESULTS: Compared
      with MED patients, diastolic pulmonary pressures trended lower (p < 0.01) and
      cardiac output higher (p < 0.001) in LVAD patients; V(30) (ex vivo ventricular
      volume yielding 30 mm Hg, an index of ventricular size) in LVAD patients was
      decreased in the LV (p < 0.05) but did not change significantly in RV. The LVAD
      support improved force generation in response to beta-adrenergic stimulation in
      isolated LV (increase in developed force from 6.3 +/- 0.6 to 18.5 +/- 4.4
      mN/m(2), p < 0.01) and RV (increase in developed force, from 10.9 +/- 2.0 to 20.5
      +/- 3.1 mN/m(2), p < 0.05) trabeculae. The LVAD patients had higher myocardial
      beta-adrenergic receptor density in LV (p < 0.01) and RV (p < 0.01). Protein
      kinase A (PKA) hyperphosphorylation of the ryanodine receptor 2 (RyR2)/calcium
      release channel was significantly reduced by LVAD in both RV and LV (p < 0.01).
      CONCLUSIONS: Improved beta-adrenergic responsiveness, normalization of the RyR2
      PKA phosphorylation, and increased beta-adrenergic receptor density in LV and RV
      after LVAD support suggest a primary role of neurohormonal environment in
      determining reverse remodeling of the beta-adrenergic pathway.

PMID- 15734610
TI  - A novel tool to assess systolic asynchrony and identify responders of cardiac
      resynchronization therapy by tissue synchronization imaging.
AB  - OBJECTIVES: This study was designed to investigate if tissue synchronization
      imaging (TSI) is useful to identify regional wall delay and predict left
      ventricular (LV) reverse remodeling after cardiac resynchronization therapy
      (CRT). BACKGROUND: Echocardiographic assessment of systolic asynchrony is helpful
      to predict a positive response to CRT. Tissue synchronization imaging is a new
      imaging technique that allows quick evaluation of regional systolic delay.
      METHODS: Tissue synchronization imaging was performed in 56 heart failure
      patients at baseline and three months after CRT. Regional wall delay was
      identified on TSI images and the time to regional peak systolic velocity (Ts) in
      LV was measured by the six-basal-six-mid-segmental model. Eight TSI parameters of
      systolic asynchrony were computed when Ts was measured in ejection phase or also
      included postsystolic shortening. RESULTS: Severe lateral wall delay occurred in
      17 patients, which predicted LV reverse remodeling (chi-square = 8.13, p =
      0.004). Among the eight quantitative parameters of asynchrony, the predictive
      values were higher for parameters that measured Ts in ejection phase than in
      postsystolic shortening. The standard deviation of Ts of 12 LV segments in
      ejection phase (Ts-SD-12-ejection) was most powerful to predict reverse
      remodeling (r = -0.61, p < 0.001) and gain in ejection fraction (r = 0.53, p <
      0.001). The area of the receiver-operating characteristic (ROC) curve was the
      largest for Ts-SD-12-ejection (0.90, p < 0.001), with a sensitivity of 87% and
      specificity of 81% at a cutoff of 34.4 ms. The combination of lateral wall delay
      with Ts-SD-12-ejection gave a sensitivity and specificity of 82% and 87%.
      CONCLUSIONS: Tissue synchronization imaging allows quick evaluation of regional
      wall delay, and combined with Ts-SD-12-ejection provides a reliable way of
      predicting reverse remodeling after CRT.

PMID- 15734611
TI  - Cross-sectional relations of electrocardiographic QRS duration to left
      ventricular dimensions: the Framingham Heart Study.
AB  - OBJECTIVES: The goal of this study was to assess the relations of
      electrocardiographic QRS duration to left ventricular (LV) measurements in
      individuals without heart failure (HF) or prior myocardial infarction (MI).
      BACKGROUND: Increased electrocardiographic QRS duration (>/=120 ms) is a marker
      of ventricular dyssynchrony. METHODS: We evaluated the relations of maximal
      electrocardiographic QRS duration to echocardiographic LV dimensions in 4,534
      Framingham Heart study participants (mean age 54 years, 57% women) without prior
      HF or MI. QRS duration was analyzed as a continuous variable and as categories
      (<100, 100 to 119, and >/=120 ms). RESULTS: In linear regression models, LV mass,
      end-diastolic dimension, and septal and posterior wall thicknesses were
      positively related to log-QRS duration, whereas fractional shortening (FS) was
      inversely related (p < 0.001). There was a significant trend for increasing LV
      mass and dimensions, and decreasing FS across categories of QRS duration (p <
      0.001). Left bundle branch block was associated with higher LV mass and lower FS
      compared with a normal QRS duration (p < 0.001). CONCLUSIONS: In our community
      based sample of individuals free of HF and MI, increasing electrocardiographic
      QRS duration was positively related to LV mass and dimensions, and inversely
      associated with LV FS. Additional investigations are warranted to elucidate the
      mechanisms underlying the observed associations.

PMID- 15734612
TI  - The need for atrial flutter ablation following pulmonary vein antrum isolation in
      patients with and without previous cardiac surgery.
AB  - OBJECTIVES: The aim of this study was to assess the incidence of atrial flutter
      (AFL) after pulmonary vein antrum isolation (PVAI) in patients with previous
      cardiac surgery (PCS) in comparison to patients without PCS and to assess the
      need for AFL ablation in both groups. BACKGROUND: Atrial fibrillation (AF) and
      AFL often co-exist. Pulmonary vein antrum isolation may be sufficient to control
      both arrhythmias. However, in patients with PCS, atrial incisions, cannulations,
      and scar areas may cause AFL recurrence despite elimination of pulmonary vein
      triggers. METHODS: Data from 1,345 patients who had PVAI were analyzed. Patients
      with a history of AFL ablation and patients who had concomitant AFL ablation
      during PVAI were excluded from analysis. Sixty-three patients constituted the PCS
      group (Group 1, age 57 +/- 13 years, 12 female) and 1,062 patients constituted
      the non-PCS group (Group 2, age 55 +/- 12 years, 212 female). Patients in Group 1
      had larger left atria, higher incidence of AFL pre-PVAI, and lower ejection
      fraction. RESULTS: There was no significant difference in post-PVAI AF recurrence
      between Groups 1 and 2, but AFL incidence after PVAI was higher in Group 1 (33%
      vs. 4%, p < 0.0001). Ablation of AFL in Group 1 patients resulted in an 86% acute
      success rate and 11% recurrence over a mean follow-up of 357 +/- 201 days.
      CONCLUSIONS: In patients with PCS, post-PVAI AF recurrence is similar to patients
      without PCS. However, history of PCS is associated with a higher recurrence of
      AFL after PVAI. In a significant number of patients with PCS, AFL ablation is
      required to achieve a cure.

PMID- 15734613
TI  - Spectrum and prognostic significance of arrhythmias on ambulatory Holter
      electrocardiogram in hypertrophic cardiomyopathy.
AB  - OBJECTIVES: The goal of this study was to assemble a profile and assess the
      significance of arrhythmias in a nontertiary-based hypertrophic cardiomyopathy
      (HCM) cohort. BACKGROUND: Hypertrophic cardiomyopathy is associated with
      arrhythmia-related consequences, particularly sudden death. Ventricular
      tachyarrhythmias on Holter electrocardiograms (ECG) have been reported as markers
      for sudden death in highly selected HCM populations. METHODS: We assessed the
      profile of ventricular and supraventricular ectopy and bradyarrhythmia on
      ambulatory 24-h Holter ECG and also related these findings to clinical outcome in
      178 HCM patients. RESULTS: Of the 178 study patients, 157 (88%) had premature
      ventricular complexes (PVCs), including 21 (12%) with >/=500 PVCs, 74 (42%) had
      couplets, 67 (37%) had supraventricular tachycardia (SVT), and 56 (31%) had
      nonsustained ventricular tachycardia (NSVT). Mean number of PVCs was 330 +/- 763
      (range 1 to 5,435) and increased with age (p < 0.01); NSVT was associated with
      greater left ventricular hypertrophy (p = 0.01) and severe symptoms (New York
      Heart Association functional classes III and IV) (p = 0.04); SVT occurred more
      commonly in patients with outflow obstruction (p = 0.02). Over a follow-up of 5.5
      +/- 3.4 years, 11 (6%) patients died suddenly (annual mortality rate, 1.1%)
      including 5 patients with NSVT. For sudden death, NSVT on Holter ECG had negative
      and positive predictive values of 95% and 9%, and sensitivity and specificity of
      45% and 69%, respectively. CONCLUSIONS: In this nontertiary-based HCM cohort,
      ventricular and supraventricular tachyarrhythmias were particularly frequent and
      demonstrated a broad spectrum on ambulatory (Holter) ECG. Paradoxically, despite
      such a highly arrhythmogenic substrate, sudden death events proved to be
      relatively uncommon. Ventricular tachyarrhythmias had a low positive and
      relatively high negative predictive value for sudden death in this HCM
      population.

PMID- 15734614
TI  - Cardiovascular morbidity and mortality in hypertensive patients with a history of
      atrial fibrillation: The Losartan Intervention For End Point Reduction in
      Hypertension (LIFE) study.
AB  - OBJECTIVES: We assessed the impact of antihypertensive treatment in hypertensive
      patients with electrocardiographic (ECG) left ventricular (LV) hypertrophy and a
      history of atrial fibrillation (AF). BACKGROUND: Optimal treatment of
      hypertensive patients with AF to reduce the risk of cardiovascular morbidity and
      mortality remains unclear. METHODS: As part of the Losartan Intervention For End
      point reduction in hypertension (LIFE) study, 342 hypertensive patients with AF
      and LV hypertrophy were assigned to losartan- or atenolol-based therapy for 1,471
      patient-years of follow-up. RESULTS: The primary composite end point
      (cardiovascular mortality, stroke, and myocardial infarction) occurred in 36
      patients in the losartan group versus 67 in the atenolol group (hazard ratio [HR]
      = 0.58, 95% confidence interval [CI] 0.39 to 0.88, p = 0.009). Cardiovascular
      deaths occurred in 20 versus 38 patients in the losartan and atenolol groups,
      respectively (HR = 0.58, 95% CI 0.33 to 0.99, p = 0.048). Stroke occurred in 18
      versus 38 patients (HR = 0.55, 95% CI 0.31 to 0.97, p = 0.039), and myocardial
      infarction in 11 versus 8 patients (p = NS). Losartan-based treatment led to
      trends toward lower all-cause mortality (30 vs. 49, HR = 0.67, 95% CI 0.42 to
      1.06, p = 0.090) and fewer pacemaker implantations (5 vs. 15, p = 0.065), whereas
      hospitalization for heart failure took place in 15 versus 26 patients and sudden
      cardiac death in 9 versus 17, respectively (both p = NS). The benefit of losartan
      was greater in patients with AF than those with sinus rhythm for the primary
      composite end point (p = 0.019) and cardiovascular mortality (p = 0.039).
      CONCLUSIONS: Losartan is more effective than atenolol-based therapy in reducing
      the risk of the primary composite end point of cardiovascular morbidity and
      mortality as well as stroke and cardiovascular death in hypertensive patients
      with ECG LV hypertrophy and AF.

PMID- 15734615
TI  - Angiotensin II receptor blockade reduces new-onset atrial fibrillation and
      subsequent stroke compared to atenolol: the Losartan Intervention For End Point
      Reduction in Hypertension (LIFE) study.
AB  - OBJECTIVES: This study was designed to evaluate whether different
      antihypertensive treatment regimens with similar blood pressure reduction have
      different effects on new-onset atrial fibrillation (AF). BACKGROUND: It is
      unknown whether angiotensin II receptor blockade is better than beta-blockade in
      preventing new-onset AF. METHODS: In the Losartan Intervention For Endpoint
      reduction in hypertension (LIFE) study 9,193 hypertensive patients and patients
      with electrocardiogram-documented left ventricular hypertrophy were randomized to
      once-daily losartan- or atenolol-based antihypertensive therapy.
      Electrocardiograms were Minnesota coded centrally, and 8,851 patients without AF
      by electrocardiogram or history, who were thus at risk of developing AF, were
      followed for 4.8 +/- 1.0 years. RESULTS: New-onset AF occurred in 150 patients
      randomized to losartan versus 221 to atenolol (6.8 vs. 10.1 per 1,000 person
      years; relative risk 0.67, 95% confidence interval [CI] 0.55 to 0.83, p < 0.001)
      despite similar blood pressure reduction. Patients receiving losartan tended to
      stay in sinus rhythm longer (1,809 +/- 225 vs. 1,709 +/- 254 days from baseline,
      p = 0.057) than those receiving atenolol. Moreover, patients with new-onset AF
      had two-, three- and fivefold increased rates, respectively, of cardiovascular
      events, stroke, and hospitalization for heart failure. There were fewer composite
      end points (n = 31 vs. 51, hazard ratio = 0.60, 95% CI 0.38 to 0.94, p = 0.03)
      and strokes (n = 19 vs. 38, hazard ratio = 0.49, 95% CI 0.29 to 0.86, p = 0.01)
      in patients who developed new-onset AF in the losartan compared to the atenolol
      treatment arm of the study. Furthermore, Cox regression analysis showed that
      losartan (21% risk reduction) and new-onset AF both independently predicted
      stroke even when adjusting for traditional risk factors. CONCLUSIONS: Our novel
      finding is that new-onset AF and associated stroke were significantly reduced by
      losartan- compared to atenolol-based antihypertensive treatment with similar
      blood pressure reduction.

PMID- 15734616
TI  - Angiotensin II inhibition and prevention of atrial fibrillation and stroke.

PMID- 15734617
TI  - A prognostic score for prediction of cardiac mortality risk after adenosine
      stress myocardial perfusion scintigraphy.
AB  - OBJECTIVES: We sought to derive and validate a score to estimate risk after
      adenosine stress. BACKGROUND: Maximizing the prognostic information extracted
      from adenosine stress myocardial perfusion scintigraphy, a commonly performed
      test, is often challenging for referring physicians. METHODS: A split-set
      validation of a score predicting cardiovascular mortality was performed in 5,873
      consecutive patients studied by adenosine stress, dual-isotope single-photon
      emission computed tomography (SPECT; follow-up 94% complete, mean 2.2 +/- 1.1
      years). RESULTS: On follow-up, 387 cardiac deaths occurred (6.6%). The Cox
      proportional hazards model most predictive of cardiac death included age, %
      myocardium ischemic, % myocardium fixed, early revascularization, dyspnea,
      diabetes mellitus, rest and peak stress heart rates, abnormal rest
      electrocardiogram (ECG), and an interaction between % myocardium ischemic and
      early revascularization (chi-square = 376). The final prognostic score was
      calculated as follows: (age [decades] x 5.19) + (% myocardium ischemic [per 10%]
      x 4.66) + (% myocardium fixed [per 10%] x 4.81) + (diabetes mellitus x 3.88) +
      (if patient treated with early revascularization, 4.51) + (if dyspnea was a
      presenting symptom, 5.47) + (resting heart rate [per 10 beats] x 2.88) - (peak
      heart rate [per 10 beats] x 1.42) + (ECG score x 1.95) - (if patient treated with
      early revascularization, % myocardium ischemic [per 10%] x 4.47). Scores of <49,
      49 to 57, and >57 identified low, intermediate, and high risk (0.9%, 3.3%, and
      9.5% cardiac death/year, respectively). Score results further risk stratified
      patients with respect to cardiac death in all categories of SPECT abnormality.
      CONCLUSIONS: We derived and validated a score incorporating data available after
      adenosine stress perfusion SPECT. This score maximizes the prognostic information
      extracted from this test and may enhance the application of this test as part of
      an overall strategy.

PMID- 15734618
TI  - Quantitative instruments for predicting risk ... and benefit.

PMID- 15734620
TI  - Noninvasive diagnosis of coronary artery disease in patients with heart failure
      and systolic dysfunction of uncertain etiology, using late gadolinium-enhanced
      cardiovascular magnetic resonance.
AB  - OBJECTIVES: We evaluated the feasibility of using late gadolinium-enhanced (LGE)
      cardiovascular magnetic resonance (CMR) to distinguish left ventricular (LV)
      systolic dysfunction related or not to coronary artery disease (CAD) in patients
      with heart failure (HF) but without clinical suspicion of CAD as the underlying
      cause. BACKGROUND: In patients with known CAD, LGE-CMR is capable of
      distinguishing LV systolic dysfunction related to CAD from dilated
      cardiomyopathy. METHODS: Seventy-one patients with HF and LV systolic
      dysfunction, without a previous history of myocardial infarction, with neither Q
      waves nor clinical data suggesting CAD, underwent both LGE-CMR and coronary
      angiography. RESULTS: Twenty-six patients (37%) had angiographically proven CAD
      (>/=70% stenosis of a major epicardial vessel) (angio [+] group), and 45 (63%)
      had unobstructed coronary arteries (angio [-] group). Twenty-one patients in the
      angio (+) group (21 of 26, 81%) showed subendocardial and/or transmural
      enhancement, whereas only 4 (9%) of 45 in the angio (-) group showed it (p <
      0.001). In 7 patients (7 of 71, 10%), we found a different pattern of mid-wall
      enhancement-namely, 3 of 26 patients in the angio (+) group and 4 of 45 in the
      angio (-) group (11% vs. 9%, p = 0.7). Mid-wall enhancement in the angio (+)
      group was distributed in segments other than those which had subendocardial
      enhancement. CONCLUSIONS: In patients with HF and LV systolic dysfunction without
      clinical suspicion of CAD, LGE-CMR is an excellent tool for classifying patients
      in relation to the presence or absence of underlying CAD. Thus, CMR might offer a
      valid alternative to coronary angiography for the detection of CAD in these
      patients.

PMID- 15734619
TI  - Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic
      plaques detected by noninvasive magnetic resonance imaging.
AB  - OBJECTIVES: We sought to elucidate the effects of 20-mg versus 5-mg atorvastatin
      on thoracic and abdominal aortic plaques. BACKGROUND: Regression of thoracic
      aortic plaques by simvastatin was demonstrated using magnetic resonance imaging
      (MRI). However, the effects of different doses of statin have not been assessed.
      METHODS: Using MRI, we investigated the effects of 20-mg versus 5-mg atorvastatin
      on thoracic and abdominal aortic plaques in 40 hypercholesterolemic patients who
      were randomized to receive either dose. Treatment effects were evaluated as
      changes in vessel wall thickness (VWT) and vessel wall area (VWA) of
      atherosclerotic lesions from baseline to 12 months of treatment. RESULTS: The 20
      mg dose induced a greater low-density lipoprotein (LDL) cholesterol reduction
      than did the 5-mg dose (-47% vs. -34%, p < 0.001). Although 20 mg and 5 mg
      reduced C-reactive protein (CRP) levels (-47% and -28%), the degree of CRP
      reduction did not differ between the two doses. The 20-mg dose reduced VWT and
      VWA of thoracic aortic plaques (-12% and -18%, p < 0.001), whereas 5 mg did not
      (+1% and +4%). Regarding abdominal aortic plaques, even 20 mg could not reduce
      VWT or VWA (-1% and +3%), but instead progression was observed with 5-mg
      treatment (+5% and +12%, p < 0.01). Notably, the degree of plaque regression in
      thoracic aorta correlated with LDL cholesterol (r = 0.64) and CRP (r = 0.49)
      reductions. Although changes in abdominal aortic plaques only weakly correlated
      with LDL cholesterol reduction (r = 0.34), they correlated with age (r = 0.41).
      CONCLUSIONS: One-year 20-mg atorvastatin treatment induced regression of thoracic
      aortic plaques with marked LDL cholesterol reduction, whereas it resulted in only
      retardation of plaque progression in abdominal aorta. Thoracic and abdominal
      aortic plaques may have different susceptibilities to lipid lowering.

PMID- 15734621
TI  - Noninvasive visualization of the cardiac venous system using multislice computed
      tomography.
AB  - OBJECTIVES: We sought to evaluate the value of multislice computed tomography
      (MSCT) to depict the cardiac venous anatomy. BACKGROUND: During cardiac
      resynchronisation therapy (CRT), left ventricular (LV) pacing is established by a
      pacemaker lead in a tributary of the coronary sinus (CS). Knowledge of the CS
      anatomy and variations may facilitate the implantation of LV leads. METHODS: The
      MSCT scans of 38 patients (34 men; age 60 +/- 12 years) were studied. Anatomical
      variants were divided in three groups, dependent on the continuity of the cardiac
      venous system at the crux cordis. The CS ostium and distances between the main
      tributaries were measured. RESULTS: The most frequently observed variant had a
      separate insertion of the CS and the small cardiac vein in the right atrium (24
      patients [63%]). In 11 patients (29%), there was continuity of the anterior and
      posterior venous system at the crux cordis. In three patients (8%), the posterior
      interventricular vein (PIV) did not connect to the CS. The mean distance from the
      PIV to the posterior vein of the left ventricle (PVLV) was 42.4 +/- 18.1 mm, from
      the PVLV to the left marginal vein (LMV) 39.9 +/- 15.6 mm, and from the LMV to
      the anterior interventricular vein 45.4 +/- 15.3 mm. The diameter of the CS
      ostium was 12.6 +/- 3.6 mm in anteroposterior and 15.5 +/- 4.5 mm in the
      superoinferior direction (p < 0.01). CONCLUSIONS: The anatomy of the CS and its
      tributaries can be evaluated using MSCT. As substantial variation in anatomy was
      observed, pre-implantation knowledge of the venous anatomy may help to decide
      whether transvenous LV lead placement for CRT is feasible.

PMID- 15734623
TI  - Quantitation of mitral valve tenting in ischemic mitral regurgitation by
      transthoracic real-time three-dimensional echocardiography.
AB  - OBJECTIVES: We sought to investigate the geometric changes of the mitral leaflets
      and annulus, clarify the maximum tenting site of the leaflets, and quantify the
      valve tenting in ischemic mitral regurgitation (MR) using three-dimensional (3D)
      echocardiography. BACKGROUND: Although the understanding of the mechanisms of
      ischemic MR has advanced recently, the geometric changes of the mitral leaflets
      and annulus have been assessed by two-dimensional echocardiography in the
      clinical setting, despite the unique configuration of the leaflets and annulus.
      METHODS: Utilizing real-time 3D echocardiography, we obtained transthoracic
      volumetric images in 12 patients with ischemic MR presenting with global left
      ventricular dysfunction and in 10 controls. Original software was used to crop
      the 3D data into 18 radial planes, and we marked the mitral annulus and leaflets
      in each plane in mid-systole. The 3D images of the leaflets and annulus were
      reconstructed for the quantitative measurements. RESULTS: In ischemic MR, the
      annulus flattened with apparent tenting of the leaflets. Maximum and mean tenting
      length were longer and tenting volume was larger in ischemic MR than control
      subjects (maximum tenting length: 9.8 +/- 2.0 mm vs. 3.1 +/- 1.2 mm, p < 0.0001,
      mean tenting length: 3.7 +/- 0.9 mm vs. 0.7 +/- 0.5 mm, p < 0.0001, tenting
      volume: 4.09 +/- 1.22 ml vs. 0.45 +/- 0.29 ml, p < 0.0001). The maximum tenting
      site was located in anterior leaflet in all patients. CONCLUSIONS: We clearly
      demonstrated 3D geometric deformity of the mitral leaflets and annulus in
      ischemic MR using novel software for creating images by 3D echocardiography. This
      technique will be helpful in making a proper decision for the surgical strategy
      in each patient.

PMID- 15734622
TI  - The quantification of absolute myocardial perfusion in humans by contrast
      echocardiography: algorithm and validation.
AB  - OBJECTIVES: We sought to test whether myocardial blood flow (MBF) can be
      quantified by myocardial contrast echocardiography (MCE) using a volumetric model
      of ultrasound contrast agent (UCA) kinetics for the description of refill curves
      after ultrasound-induced microsphere destruction. BACKGROUND: Absolute myocardial
      perfusion or MBF (ml.min(-1).g(-1)) is the gold standard to assess myocardial
      blood supply, and so far it could not be obtained by ultrasound. METHODS: The
      volumetric model yielded MBF = rBV.beta/rho(T), where rho(T) equals tissue
      density. The relative myocardial blood volume rBV and its exchange frequency beta
      were derived from UCA refill sequences. Healthy volunteers underwent MCE and
      positron emission tomography (PET) at rest (group I: n = 15; group II: n = 5) and
      during adenosine-induced hyperemia (group II). Fifteen patients with coronary
      artery disease underwent simultaneous MCE and intracoronary Doppler measurements
      before and during intracoronary adenosine injection. RESULTS: In vitro
      experiments confirmed the volumetric model and the reliable determination of rBV
      and beta for physiologic flow velocities. In group I, 187 of 240 segments were
      analyzable by MCE, and a linear relation was found between MCE and PET perfusion
      data (y = 0.899x + 0.079; r(2) = 0.88). In group II, resting and hyperemic
      perfusion data showed good agreement between MCE and PET (y = 1.011x + 0.124;
      r(2) = 0.92). In patients, coronary stenosis varied between 0% to 89%, and
      myocardial perfusion reserve was in good agreement with coronary flow velocity
      reserve (y = 0.92x + 0.14; r(2) = 0.73). CONCLUSIONS: The volumetric model of UCA
      kinetics allows the quantification of MBF in humans using MCE and provides the
      basis for the noninvasive and quantitative assessment of coronary artery disease.

PMID- 15734624
TI  - Broad-beam spectral Doppler sonification of the vena contracta using matrix-array
      technology: A new solution for semi-automated quantification of mitral
      regurgitant flow volume and orifice area.
AB  - OBJECTIVES: The objective of this study was to evaluate broad-beam spectral
      Doppler sonification of the vena contracta using a matrix-array transducer for
      quantification of mitral regurgitation (MR). BACKGROUND: Noninvasive assessment
      of the severity of valvular regurgitation remains challenging. A recent technique
      measures regurgitant flow directly at the vena contracta based on the product of
      velocity times backscattered Doppler power (proportional to orifice area). That
      approach, however, has been limited by relatively narrow conventional beamwidths.
      Matrix-array transducers, recently developed for three-dimensional imaging, can
      potentially provide broader beams. Therefore, we addressed the hypothesis that
      deliberate broadening of the Doppler beam can encompass larger regurgitant cross
      sectional areas to capture a broader range of regurgitant flows. METHODS: A
      matrix-array transducer system was modified to provide a three-dimensionally
      expanded spectral Doppler sample volume. Calculations of orifice area, flow rate,
      and regurgitant stroke volume (RSV) from Doppler power were automated on board a
      routinely used echocardiographic scanner and tested in vitro. In 24 patients with
      isolated MR, RSV was compared with magnetic resonance imaging (MRI) mitral inflow
      minus aortic outflow from phase-velocity maps. RESULTS: The calculated flow rate
      and RSV correlated and agreed well with reference values in vitro (r = 0.98 to
      0.99) and in patients (r = 0.93, mean difference 0.4 +/- 3.2 ml, p = NS vs. 0),
      with sufficient sonification to measure flow orifices up to 0.85 cm in diameter.
      Agreement with MRI was comparable in 17 patients with central and seven with
      eccentric jets (p = NS vs. 0). CONCLUSIONS: The broad-beam spectral Doppler
      technique provides accurate, largely automated quantification of regurgitant flow
      rate and integrated RSV directly at the lesion. The accuracy related to broader
      sonification is made possible by the new matrix-array transducer design.

PMID- 15734625
TI  - Detection of peripheral vascular stenosis by assessing skeletal muscle flow
      reserve.
AB  - OBJECTIVES: We sought to determine whether the severity of peripheral arterial
      disease (PAD) can be assessed by measuring blood flow reserve in limb skeletal
      muscle with contrast-enhanced ultrasound (CEU). BACKGROUND: Noninvasive imaging
      of distal limb perfusion could improve management of patients with PAD by
      evaluating the impact of large and small vessel disease, and collateral flow.
      METHODS: In 12 dogs, blood flow in the quadriceps femoris was measured by CEU at
      rest and during either electrostimulated contractile exercise or adenosine
      infusion. Femoral artery blood flow was measured by Doppler ultrasound. Studies
      were performed in the absence and presence of either moderate or severe stenosis
      (pressure gradient of 10 to 20 mm Hg and >20 mm Hg, respectively). RESULTS:
      Resting femoral artery blood flow progressively decreased with stenosis severity,
      while resting skeletal muscle flow was reduced only with severe stenosis (52 +/-
      21% of baseline, p < 0.05), indicating the presence of collateral flow. Skeletal
      muscle flow reserve during contractile exercise or adenosine decreased
      incrementally with increasing stenosis severity (p < 0.01). The stenotic pressure
      gradient correlated with skeletal muscle flow reserve for exercise and adenosine
      (r = 0.70 for both, p < 0.01). CONCLUSIONS: Contrast-enhanced ultrasound of limb
      skeletal muscle can be used to assess the severity of PAD by measuring muscle
      flow reserve during either contractile exercise or pharmacologic vasodilation.
      Unlike currently used methods, this technique may provide a measure of the
      physiologic effects of large- and small-vessel PAD, and the influence of
      collateral perfusion.

PMID- 15734626
TI  - Better outcome after pediatric defibrillation dosage than adult dosage in a swine
      model of pediatric ventricular fibrillation.
AB  - OBJECTIVES: This study was designed to compare outcome after adult defibrillation
      dosing versus pediatric dosing in a piglet model of prolonged prehospital
      ventricular fibrillation (VF). BACKGROUND: Weight-based 2 to 4 J/kg monophasic
      defibrillation dosing is recommended for children in VF, but impractical for
      automated external defibrillator (AED) use. Present AEDs can only provide adult
      shock doses or newly developed attenuated adult doses intended for children. A
      single escalating energy sequence (50/75/86 J) of attenuated adult-dose biphasic
      shocks (pediatric dosing) is at least as effective as escalating monophasic
      weight-based dosing for prolonged VF in piglets, but this approach has not been
      compared to standard adult biphasic dosing. METHODS: Following 7 min of untreated
      VF, piglets weighing 13 to 26 kg (19 +/- 1 kg) received either biphasic 50/75/86
      J (pediatric dose) or biphasic 200/300/360 J (adult dose) therapies during
      simulated prehospital life support. RESULTS: Return of spontaneous circulation
      was attained in 15 of 16 pediatric-dose piglets and 14 of 16 adult-dose piglets.
      Four hours postresuscitation, pediatric dosing resulted in fewer elevations of
      cardiac troponin T (0 of 12 piglets vs. 6 of 11 piglets, p = 0.005) and less
      depression of left ventricular ejection fraction (p < 0.05). Most importantly,
      more piglets survived to 24 h with good neurologic scores after pediatric shocks
      than adult shocks (13 of 16 piglets vs. 4 of 16 piglets, p = 0.004). CONCLUSIONS:
      In this model, pediatric shocks resulted in superior outcome compared with adult
      shocks. These data suggest that adult defibrillation dosing may be harmful to
      pediatric patients with VF and support the use of attenuating electrodes with
      adult biphasic AEDs to defibrillate children.

PMID- 15734628
TI  - Highlights of the 2004 transcatheter cardiovascular therapeutics (TCT) annual
      meeting: clinical implications.

PMID- 15734627
TI  - The year in clinical electrophysiology.

PMID- 15734629
TI  - Angiographic patterns of restenosis after paclitaxel-eluting stent implantation.

PMID- 15734630
TI  - Rescue angioplasty--the MERLIN trial.

PMID- 15734633
TI  - Definition of failed lysis may have influenced outcome in the MERLIN trial.

PMID- 15734634
TI  - Influence of pretreatment systolic blood pressure on benefit from carvedilol in
      severe chronic heart failure patients.

PMID- 15734635
TI  - Should the lack of feasibility of conducting controlled trials influence evidence
      based guidelines?

PMID- 15734639
TI  - Biolex, Inc.: pharmaceutical production in plants.

PMID- 15734640
TI  - Making a new turn in matrix metalloprotease inhibition.
AB  - The paradigm for matrix metalloprotease inhibition combines active site tailoring
      and catalytic zinc ligation. But, selectivity has been difficult. Now, Engel et
      al. present novel compounds, completely selective for MMP-13, with a unique
      binding mode.

PMID- 15734641
TI  - New prodiginines from a ketosynthase swap.
AB  - The prodiginine antibiotics exhibit antitumor and immunosuppressive activity. In
      this issue of Chemistry & Biology, Reynolds and coworkers demonstrate that new
      prodiginines can be obtained by substituting a FabH ketosynthase for the RedP
      ketosynthase in the undecylprodiginine biosynthetic gene cluster.

PMID- 15734642
TI  - Enzyme-assisted antibiotic engineering--the Wright way.

PMID- 15734643
TI  - Creating small-molecule-dependent switches to modulate biological functions.
AB  - Biological small-molecule-dependent switches sense external chemical signals and
      transduce them into appropriate internal signals and cellular responses.
      Artificial molecular switches that control the function of any protein of
      interest using a small molecule are powerful tools for studying biology because
      they enable cellular responses to be controlled by inputs chosen by researcher.
      Furthermore, these switches can combine the generality of genetic regulation with
      the reversibility and temporal control afforded by small molecules. Three
      approaches to creating molecular switches include altering a natural switch to
      recognize new exogenous ligands, engineering novel allosteric responses to ligand
      binding, or enforcing protein localization with chemical dimerizers. Here, we
      discuss the development of small-molecule-dependent switches that control in a
      general fashion transcriptional activation, translational initiation, and protein
      activity posttranslationally.

PMID- 15734644
TI  - Exploring new chemical space by stereocontrolled diversity-oriented synthesis.
AB  - Natural products that act as highly specific, small-molecule protein-binding
      agents and as modulators of protein-protein interactions are highly complex and
      exhibit functional groups with three-dimensional and stereochemical diversity.
      The complex three-dimensional display of chiral functional groups appears to be
      crucial for exhibiting specificity in protein binding and in differentiating
      between closely related proteins. The development of methods that allow a high
      throughput access to three-dimensional, skelatally complex, polycyclic compounds
      having few asymmetric diversity sites is essential and a highly challenging task.
      In the postgenomic chemical biology age, in which there is a great desire to
      understand protein-protein interactions and to dissect protein networking-based
      signaling pathways by small molecules, the need for developing "stereocontrolled,
      diversity-oriented synthesis" methods to generate natural product-like libraries
      is of utmost importance.

PMID- 15734645
TI  - Structural basis for the highly selective inhibition of MMP-13.
AB  - Inhibitors for matrix metalloproteinases (MMPs) are under investigation for the
      treatment of cancer, arthritis, and cardiovascular disease. Here, we report a
      class of highly selective MMP-13 inhibitors (pyrimidine dicarboxamides) that
      exhibit no detectable activity against other MMPs. The high-resolution X-ray
      structures of three molecules of this series bound to MMP-13 reveal a novel
      binding mode characterized by the absence of interactions between the inhibitors
      and the catalytic zinc. The inhibitors bind in the S1' pocket and extend into an
      additional S1' side pocket, which is unique to MMP-13. We analyze the
      determinants for selectivity and describe the rational design of improved
      compounds with low nanomolar affinity.

PMID- 15734646
TI  - Production of branched-chain alkylprodiginines in S. coelicolor by replacement of
      the 3-ketoacyl ACP synthase III initiation enzyme, RedP.
AB  - The enzyme RedP is thought to initiate the biosynthesis of the undecylpyrolle
      component of the antibiotic undecylprodiginine produced by Streptomyces
      coelicolor. RedP has homology to FabH, which initiates fatty acid biosynthesis by
      condensing the appropriate acyl-CoA starter unit with malonyl ACP. We have
      generated a redP-deletion mutant of S. coelicolor M511 (SJM1) and shown that it
      produces reduced levels of prodiginines and two new analogs,
      methylundecylprodiginine and methyldodecylprodiginine. Incorporation studies with
      perdeuterated valine were consistent with these being generated using
      methylbutyryl-CoA and isobutyryl-CoA as starter units, respectively. Plasmid
      based expression of a streptomycete fabH in the SJM1 mutant led to restoration of
      overall prodiginine titers but the same overall ratio of undecylprodiginines and
      novel prodiginines. Thus, the redP FabH can be replaced by FabH enzymes with
      different substrate specificities and provides a method for generating novel
      prodiginines.

PMID- 15734647
TI  - Coevolution of protein and RNA structures within a highly conserved ribosomal
      domain.
AB  - The X-ray crystal structure of a ribosomal L11-rRNA complex with chloroplast-like
      mutations in both protein and rRNA is presented. The global structure is almost
      identical to that of the wild-type (bacterial) complex, with only a small
      movement of the protein alpha helix away from the surface of the RNA required to
      accommodate the altered protein residue. In contrast, the specific hydrogen
      bonding pattern of the mutated residues is substantially different, and now
      includes a direct interaction between the protein side chain and an RNA base edge
      and a water-mediated contact. Comparison of the two structures allows the
      observations of sequence variation and relative affinities of wild-type and
      mutant complexes to be clearly rationalized, but reinforces the concept that
      there is no single simple code for protein-RNA recognition.

PMID- 15734648
TI  - TINS, target immobilized NMR screening: an efficient and sensitive method for
      ligand discovery.
AB  - We propose a ligand screening method, called TINS (target immobilized NMR
      screening), which reduces the amount of target required for the fragment-based
      approach to drug discovery. Binding is detected by comparing 1D NMR spectra of
      compound mixtures in the presence of a target immobilized on a solid support to a
      control sample. The method has been validated by the detection of a variety of
      ligands for protein and nucleic acid targets (K(D) from 60 to 5000 muM). The
      ligand binding capacity of a protein was undiminished after 2000 different
      compounds had been applied, indicating the potential to apply the assay for
      screening typical fragment libraries. TINS can be used in competition mode,
      allowing rapid characterization of the ligand binding site. TINS may allow
      screening of targets that are difficult to produce or that are insoluble, such as
      membrane proteins.

PMID- 15734649
TI  - Stereospecific effects determine the structure of a four-way DNA junction.
AB  - Conversion of a centrally located phosphate group to an electrically neutral
      methyl phosphonate in a four-way DNA junction can exert a major influence on its
      conformation. However, the effect is strongly dependent on stereochemistry.
      Substitution of the proR oxygen atom by methyl leads to conformational transition
      to the stacking conformer that places this phosphate at the point of strand
      exchange. By contrast, corresponding modification of the proS oxygen destabilizes
      this conformation of the junction. Single-molecule analysis shows that both
      molecules are in a dynamic equilibrium between alternative stacking conformers,
      but the configuration of the methyl phosphonate determines the bias of the
      conformational equilibrium. It is likely that the stereochemical environment of
      the methyl group affects the interaction with metal ions in the center of the
      junction.

PMID- 15734650
TI  - Chimeric streptogramin-tyrocidine antibiotics that overcome streptogramin
      resistance.
AB  - Streptogramin antibiotics are comprised of two distinct chemical components: the
      type A polyketides and the type B cyclic depsipeptides. Clinical resistance to
      the type B streptogramins can occur via enzymatic degradation catalyzed by the
      lyase Vgb or by target modification through the action of Erm ribosomal RNA
      methyltransferases. We have prepared through chemical and chemo-enzymatic
      approaches a series of chimeric antibiotics composed of elements of type B
      streptogramins and the membrane-active antibiotic tyrocidine that evade these
      resistance mechanisms. These new compounds show broad antibiotic activity against
      gram-positive bacteria including a number of important pathogens, and chimeras
      appear to function by a mechanism that is distinct from their parent antibiotics.
      These results allow for the development of a brand new class of antibiotics with
      the ability to evade type B streptogramin-resistance mechanisms.

PMID- 15734652
TI  - Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in
      Streptomyces rochei.
AB  - The lankacidin biosynthetic gene cluster in Streptomyces rochei strain 7434AN4
      was found to span 31 kb of the giant linear plasmid pSLA2-L and contain a
      polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid gene
      (lkcA), type I PKS genes, and pyrroloquinoline quinone (PQQ) biosynthetic genes
      (lkcK-lkcO). Feeding of PQQ to a pqq mutant restored the lankacidin production,
      suggesting its crucial role in an oxidation process. However, formation of the 17
      membered macrocyclic ring was not catalyzed by PQQ-dependent dehydrogenase
      (Orf23), but was by flavin-dependent amine oxidase (LkcE). Compound LC-KA05
      isolated from an lkcE disruptant was an acyclic intermediate lacking the C2-C18
      linkage. These results suggested a cyclization mechanism for the synthesis of the
      lankacidin macrocyclic skeleton.

PMID- 15734653
TI  - RNAi-based discovery and validation of new drug targets in filarial nematodes.
AB  - Human filarial nematodes cause river blindness and lymphatic filariasis, both of
      which are diseases that produce considerable morbidity. Control of these diseases
      relies on drug treatments that are ineffective against macrofilariae and are
      threatened by the development of resistance. New validated drug targets are
      required to allow development of new classes of antifilarial drugs. To identify
      and validate potential new drug targets, we propose a collaborative research
      strategy utilizing bioinformatic filters and assessment of gene function by RNA
      interference in Caenorhabditis elegans and Brugia malayi.

PMID- 15734651
TI  - A neoceptor approach to unraveling microscopic interactions between the human A2A
      adenosine receptor and its agonists.
AB  - Strategically mutated neoceptors, e.g., with anionic residues in TMs 3 and 7
      intended for pairing with positively charged amine-modified nucleosides, were
      derived from the antiinflammatory A(2A) adenosine receptor (AR). Adenosine
      derivatives functionalized at the 5', 2, and N(6) positions were synthesized. The
      T88D mutation selectively enhanced the binding of the chain-length-optimized 5'
      (2-aminoethyl)uronamide but not 5'-(2-hydroxyethyl)uronamide, suggesting a
      critical role of the positively charged amine. Combination of this modification
      with the N(6)-(2-methylbenzyl) group enhanced affinity at the Q89D- and N181D-
      but not the T88D-A(2A)AR. Amino groups placed near the 2- or N(6)-position only
      slightly affected the binding to mutant receptors. The 5'-hydrazide MRS3412 was
      670- and 161-fold enhanced, in binding and functionally, respectively, at the
      Q89D-A(2A)AR compared to the wild-type. Thus, we identified and modeled pairs of
      A(2A)AR-derived neoceptor-neoligand, which are pharmacologically orthogonal with
      respect to the native species.

PMID- 15734654
TI  - Mining nematode genome data for novel drug targets.
AB  - Expressed sequence tag projects have currently produced over 400 000 partial gene
      sequences from more than 30 nematode species and the full genomic sequences of
      selected nematodes are being determined. In addition, functional analyses in the
      model nematode Caenorhabditis elegans have addressed the role of almost all genes
      predicted by the genome sequence. This recent explosion in the amount of
      available nematode DNA sequences, coupled with new gene function data, provides
      an unprecedented opportunity to identify pre-validated drug targets through
      efficient mining of nematode genomic databases. This article describes the
      various information sources available and strategies that can expedite this
      process.

PMID- 15734655
TI  - Is Giardia a living fossil?
AB  - Despite enormous efforts, the patterns of the rise of eukaryotic life on Earth
      are not clearly defined. The ability of eukaryotes to produce energy using oxygen
      and sugars was a key factor in advancing life on Earth towards complex
      multicellular organisms. However, this was not the only way to produce energy and
      survive. Mitochondria probably appeared soon after the oxygen increase in the
      Earth's atmosphere but many microaerophilic protists require little or no oxygen
      to survive. New ultrastructural, biochemical and molecular phylogeny data about
      structures and processes involved in the generation of energy by currently known
      protists have forced the revision of understanding of the "tree of life".

PMID- 15734656
TI  - A case for a Glossina genome project.
AB  - Given the medical and agricultural significance of Glossina, knowledge of the
      genomic aspects of the vector and vector-pathogen interactions are a high
      priority. In preparation for a full genome sequence initiative, an extensive set
      of expressed sequence tags (ESTs) has been generated from tissue-specific
      normalized libraries. In addition, bacterial artificial chromosome (BAC)
      libraries are being constructed, and information on the genome structure and size
      from different species has been obtained. An international consortium is now in
      place to further efforts to lead to a full genome project.

PMID- 15734657
TI  - Vaccine-linked chemotherapy: can schistosomiasis control benefit from an
      integrated approach?
AB  - The present strong emphasis on gross organ pathology (liver, kidneys, bladder) in
      schistosomiasis needs to be replaced with a more balanced view of the disease
      that also takes into account systemic symptoms that are less easy to assess, such
      as retarded growth, cognitive development and the effect of continuing low-level
      blood loss. Access to better estimates of disease burdens, morbidity and
      mortality is delivering results that bring into question the wisdom of
      downgrading the impact of the disease. In this scenario, the simplistic approach
      of exclusive drug treatment might not be sufficient and, in the worst-case
      scenario, might even exacerbate pathology. To meet this challenge, the
      repositioning of vaccines within the totality of disease control through the
      combined use of chemotherapy and vaccination is recommended as the basis for a
      novel, more-versatile approach to control. Studies on human correlate responses
      in endemic areas have opened the way to assess the protective value of specific
      antigens through the cytokine responses and antibodies they elicit. Moreover,
      vaccine formulations based on novel adjuvants could improve the final outcome
      through selective manipulation of the immune response. Thus, the tools of vaccine
      linked chemotherapy are in principle already available and could shortly be put
      to the test in clinical trials.

PMID- 15734658
TI  - How many functional transport pathways does Plasmodium falciparum induce in the
      membrane of its host erythrocyte?
AB  - Intraerythrocytic malaria parasites induce considerable change in the
      permeability of the membrane of their host cell. Using classical techniques of
      radiolabel uptake and iso-osmotic lysis, the permeability characteristics of the
      host-cell membrane have been determined. In a recent analysis of these results,
      we concluded that there are at least two types of channel that conform to the
      data: a low copy number (four channels per cell) type that mediates the transport
      of cations, anions and most other osmolytes that were tested, and a high copy
      number (300-400 channels per cell) type that is an anion channel that could also
      mediate the translocation of purine nucleosides. Patch-clamping experiments using
      cells infected with Plasmodium falciparum reveal 200-1000 anion channels of more
      than one type that are of host-cell endogenous provenance. Recent reports show
      that parasites can grow normally in erythrocytes that lack these endogenous
      agencies and in which the anion channels are not expressed, although their
      osmolyte permeability is present. We suggest that only the latter type of channel
      is important for normal development of the parasite.

PMID- 15734659
TI  - Are Tritrichomonas foetus and Tritrichomonas suis synonyms?
AB  - Tritrichomonas suis, a tritrichomonad of pigs, and the related species
      Tritrichomonas foetus, a tritrichomonad of cattle, are morphologically identical.
      The taxonomic relationship between these two tritrichomonads has been questioned
      ever since they were established as distinct species in 1843 and 1928,
      respectively. Here, we compare the similarities of morphology, ultrastructure,
      distribution, host specificity, characteristics of in vitro cultivation,
      immunology, biochemistry and analysis of molecular data from published sources
      between these two species. All data indicate that these two tritrichomonad
      species are identical. Thus, we propose that T. foetus and T. suis are synonyms.

PMID- 15734660
TI  - Satoshi Omura: in pursuit of nature's bounty.
AB  - Professor Satoshi Omura has spent over 40 years searching for bioactive compounds
      in naturally occurring microorganisms, discovering more than 330 biomedically and
      commercially significant compounds in the process. The discovery, development and
      delivery of the drug ivermectin has pioneered the way for subsequent partnerships
      between the public and private sectors, as well as international collaborations
      and drug donation programmes. It has involved a variety of ground-breaking steps,
      providing a curative drug that will help rid Africa and the world of at least one
      of the most devastating of all human diseases, onchocerciasis. It has also
      improved the health of pets and livestock around the globe, and encouraged
      development of a community-based delivery mechanism that could herald a
      revolution in public health care in Africa.

PMID- 15734661
TI  - Cryptosporidium excystation and invasion: getting to the guts of the matter.
AB  - Cryptosporidium parvum excystation and host cell invasion have been characterized
      in some detail ultrastructurally. However, until recently, the biochemical and
      molecular basis of host-parasite interactions and parasite- and host-specific
      molecules involved in excystation, motility and host cell invasion have been
      poorly understood. This article describes our understanding of Cryptosporidium
      excystation and the events leading to host cell invasion, and draws from
      information available about these processes in other apicomplexans. Many
      questions remain but, once the specific mechanisms are identified, they could
      prove to be novel targets for drug delivery.

PMID- 15734662
TI  - Schistosomes: the road from host-parasite interactions to vaccines in clinical
      trials.
AB  - Insights over recent years into the interactions between helminths, including
      schistosomes, and the immune system have generated new concepts in immunology and
      significant advances in vaccine strategies. Here, we report recent advances that
      substantially increase our understanding of the nature of the host innate and
      adaptive responses to schistosomes and on strategies elaborated by the parasite
      to manipulate such responses. We also describe the long road that has allowed us
      to move from the identification of an anti-schistosome vaccine candidate, a 28kDa
      glutathione-S-transferase, to its recent evaluation in human clinical trials.

PMID- 15734663
TI  - What is and what is not 'Fahr's disease'.
AB  - Bilateral almost symmetric calcification involving striatum, pallidum with or
      without deposits in dentate nucleus, thalamus and white matter is reported from
      asymptomatic individuals to a variety of neurological conditions including
      autosomal dominant inheritance to pseudo-pseudohypoparathyroidism. While
      bilateral striopallidodentate calcinosis is commonly referred to as 'Fahr's
      disease' (a misnomer), there are 35 additional names used in the literature for
      the same condition. Secondary bilateral calcification is also reported in a
      variety of genetic, developmental, metabolic, infectious and other conditions. In
      autosomal dominant or sporadic bilateral striopallidodentate calcinosis no known
      calcium metabolism abnormalities are known to date. Clinically, parkinsonism or
      other movement disorders appear to be the most common presentation, followed by
      cognitive impairment and ataxia. When presence of movement disorder, cognitive
      impairment and ataxia are present, a computed tomography scan of the head should
      be considered to rule-in or rule-out calcium deposits. Calcium and other mineral
      deposits cannot be linked to a single chromosomal locus. Further genetic studies
      to identify the chromosomal locus for the disease are in progress.

PMID- 15734665
TI  - Is there a relationship between Parkinson's disease and obsessive-compulsive
      disorder?
AB  - Obsessive-compulsive (OC) symptoms and obsessive-compulsive disorder (OCD) have
      been reported in Parkinson's disease (PD). This is interpreted as an indirect
      evidence for the involvement of frontobasal ganglia circuitry in OCD. However,
      the evidence for relationship between the OC symptoms and PD is inconsistent.
      This study systematically assessed OC symptoms and OCD in non-demented idiopathic
      PD patients (n=69) and matched medically ill controls (n=69). The cases did not
      differ from controls with respect to OC symptoms, clinical and subclinical OCD,
      tics and other psychiatric diagnoses. There was no relationship between severity
      of PD and OC symptoms. The findings do not support relationship between OCD and
      PD. While the findings of this study do not in any way rule out the involvement
      of frontobasal ganglia circuitry in OCD, it is speculated that the involvement of
      different circuitry in the pathophysiology of OCD and PD explain the lack of
      association between PD and OCD.

PMID- 15734664
TI  - Statins, cholesterol, Co-enzyme Q10, and Parkinson's disease.
AB  - 'Statins', drugs that lower cholesterol are widely used. Statins block
      cholesterol in the body and brain by inhibiting HMG-Co-A reductase. This pathway
      is shared by CoQ-10. An unintended consequence of the statins is lowering of CoQ
      10. As CoQ-10 may play a role in PD, its possible statins may worsen PD. Such a
      report has appeared. Statins came into wide use in 1997-1998, 6 years before our
      study began. Thus 74% of our patients on a statin had a PD duration of 1-6 years
      versus 56% of our patients not on a statin. A direct comparison of patients on a
      statin and not on a statin would bias the study in favor of the statins: patients
      on a statin would have a shorter disease duration and less advanced PD. Therefore
      we divided the patients into two groups. Group I consisted of 128 patients on a
      statin, and 252 not on a statin who had PD for 1-6 years. In this group, disease
      severity (Hoehn & Yahr Stage), levodopa dose, Co-enzyme Q10 use, prevalence of
      'wearing off', dyskinesia and dementia were similar. Group II consisted of 45
      patients on a statin and 200 patients not on a statin who had PD for 7-22 years.
      In this group disease severity, levodopa dose, Co-enzyme Q10 use, prevalence of
      wearing off, dyskinesia and dementia were similar. Statins although they may
      affect Co-enzyme Q10 levels in the body and the brain, do not worsen PD at least
      as assessed by stage, and prevalence of wearing-off, dyskinesia, and dementia.

PMID- 15734666
TI  - Bilateral subthalamic nucleus stimulation improves health-related quality of life
      in Parkinsonian patients.
AB  - Parkinson's disease (PD) is a common neurological disorder. Recently, bilateral
      deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an
      option in the treatment of severe PD. We measured the health-related quality of
      life (HRQoL) of 27 parkinsonian patients, who underwent a bilateral STN
      operation. The instruments used for the evaluation of the HRQoL were the
      Parkinson's Disease Questionnaire (PDQ-39) and the Finnish version of the
      Nottingham Health Profile (NHP). We found that the quality of life significantly
      improved when measured with both HRQoL scales. Clinical improvement and
      improvement in HRQoL were positively correlated.

PMID- 15734667
TI  - The effect of directing attention during walking under dual-task conditions in
      Parkinson's disease.
AB  - The aim of this study was to investigate the effect of directing attention on
      walking performance under dual-task conditions in people with Parkinson's disease
      (PD). Twelve subjects with mild to moderate PD were tested 'on' medication.
      Subjects walked at comfortable speed under 2 baseline conditions: (i) walking
      with hands-free, no specific instructions and (ii) walking carrying a tray and
      glasses, no specific instructions; and 2 experimental conditions: (i) walking
      carrying a tray and glasses with instructions to direct attention towards walking
      and (ii) walking carrying a tray and glasses with instructions to direct
      attention towards the tray and glasses. When instructed to direct their attention
      towards walking while carrying the tray and glasses, subjects walked faster
      (P=0.003) and with longer strides (P<0.001) than when they were given no specific
      instructions. These improvements in walking were achieved without any significant
      adverse effect on carrying the tray of glasses. The improvement obtained was to a
      level comparable to that achieved when subjects walked with their hands-free.
      This suggests that specific instructions can be used to manipulate attention to
      enhance the performance of everyday dual-tasks in people with mild to moderate
      PD.

PMID- 15734668
TI  - Effect of zonisamide on essential tremor: a pilot crossover study in comparison
      with arotinolol.
AB  - We performed a pilot, crossover trial of zonisamide (ZNS) on essential tremor
      patients. Patients were randomly selected to start either ZNS or arotinolol
      treatment for 2 weeks. After a washout period, the patients were switched to an
      alternative drug. The assessment of tremor was carried out using the Fahn-Tolosa
      Marin's clinical rating scale for tremor at baseline and 2 weeks after
      administration of each drug. There was a significant improvement after ZNS and
      arotinolol administration compared with the baseline. There was no significant
      difference in the antitremor effect between ZNS and arotinolol; however, ZNS was
      more effective for tremors of cranial nerve areas. Although the number of
      enrolled patients was limited in the present study, this open-label pilot study
      suggests that ZNS may have a therapeutic potential for essential tremor. A
      controlled trial of this drug in the future would be valuable.

PMID- 15734669
TI  - Repetitive involuntary leg movements in patients with brainstem lesions involving
      the pontine tegmentum: evidence for a pontine inhibitory region in humans.
AB  - Repetitive involuntary limbs movements have been mostly reported in patients with
      extensive brainstem pathologies, but the region responsible is unknown. We
      describe two patients with progressive basilar artery infarcts who showed
      automatic stepping and one patient with an osmotic demyelination disorder who
      showed periodic involuntary leg movements. By subtracting diffusion-weighted
      images before and after the development of repetitive involuntary leg movements,
      the brainstem lesion responsible for the involuntary movements was distinctively
      located in the vicinity of the pontine tegmentum, which is known as the pontine
      inhibitory region in animal studies.

PMID- 15734670
TI  - Memory perception and strategy use in Parkinson's disease.
AB  - Although there is growing support for the existence of memory deficits within
      Parkinson's disease (PD), little has been done to evaluate the extent to which PD
      patients demonstrate differences in their use of metacognitive strategies. In the
      present study, 79 PD patients (46 men and 33 women) and 49 age-matched healthy
      participants (19 men and 30 women) were compared on a metamemory questionnaire.
      PD patients reported significantly less strategy-use than age-matched controls,
      particularly with regards to external memory strategies (such as making lists).
      This suggests that auxiliary treatments such as memory strategy training might be
      effective in this population.

PMID- 15734671
TI  - Graves' disease associated with spasmodic truncal flexion.
AB  - A 40-year-old Chinese man was admitted with 1-2 Hz spasmodic truncal flexion
      resembling myoclonus. He was known to be thyrotoxic, and had defaulted
      antithyroid therapy. Clinical examination revealed truncal flexion from
      contraction of the rectus abdominis, with no involvement of limbs or face and no
      jerking in sleep. He was biochemically thyrotoxic. Treatment with clonazepam and
      propylthiouracil resulted in resolution of the myoclonic jerks within the next 3
      weeks. He stopped taking clonazepam within the next 3 months with no recurrence
      of myoclonus. He remained well until he stopped taking his antithyroid
      medications 9 months later, when he developed spasmodic truncal jerking again.
      Biochemical tests confirmed that he was hyperthyroid at this time. These
      movements ceased within a month of compliance with antithyroid therapy, and he
      has been well since. MRI of the brain and thoracic spine were unremarkable.
      Thyrotoxicosis is known to cause chorea and tremors, and has rarely been
      described in association with myoclonus.

PMID- 15734673
TI  - Cyanide-induced akinetic rigid syndrome: clinical, MRI, FDG-PET, beta-CIT and
      HMPAO SPECT findings.
AB  - A 35-year-old female ingested a lethal dose of potassium cyanide in a suicide
      attempt. She survived following antidote therapy and intensive care. Following
      artificial coma she presented with an agitative state for several days followed
      by akinetic mutism, buccofacial and ideomotoric aphasia. Severe rigid-akinetic
      syndrome, dysarthria, dysphagia and generalized dystonia developed weeks later.
      MRI revealed lesions in the caudate and lentiform nuclei, precentral cortex, and
      cerebellum. SPECT by [123-I] 2 beta-carbomethoxy-3-beta-(4-iodophenyl)-Tropan on
      two occasions revealed progressive loss of dopamine transporter suggestive of
      nigral neuronal apoptosis. Striatal and frontal hypometabolism and hypoperfusion
      were found by FDG-PET and HMPAO SPECT.

PMID- 15734672
TI  - Secondary generalized dystonia without basal ganglia damage.
AB  - We report the case of a woman who developed generalized dystonia, severe
      cognitive deficits and dysphagia following an overdose of the hypoglycaemic drug,
      sulphonylurea. The MRI reveals frontal and temporal lobe atrophy, but no evidence
      of damage to the basal ganglia. This case adds to the small number of previously
      reported cases with secondary dystonia seemingly due to cortical rather than
      subcortical damage.

PMID- 15734674
TI  - Plasma homocysteine levels in Parkinson's disease: role of antiparkinsonian
      medications.
AB  - Elevated plasma homocysteine (Hcy) concentrations have been reported in L-dopa
      treated Parkinson's disease (PD) patients, suggesting that L-dopa treatment is an
      acquired cause of hyperhomocysteinemia. Aim of this study is to evaluate the
      effects of different antiparkinsonian drugs on Hcy concentrations. We compared
      Hcy, B(12) and folate levels in 45 PD patients (15 treated with dopamine
      agonists, 15 with L-dopa and 15 with L-dopa plus a catechol-O-methyltransferase
      inhibitor (COMT-I) and in 15 controls. Analysis of data revealed that L-dopa
      administration significantly increases Hcy concentrations and that the addition
      of COMT-I effectively reduces the homocysteinemia.

PMID- 15734675
TI  - Limited efficacy of levetiracetam on myoclonus of different etiologies.
AB  - Levetiracetam is a relatively new antiepileptic drug, which has been reported to
      have promising antimyoclonic properties, especially in posthypoxic myoclonus,
      progressive myoclonic epilepsy (PME) and spinal myoclonus. Eight patients with
      intractable myoclonus of various etiologies were given levetiracetam as add-on
      therapy in an open-label trial. Physician and patient self-assessments were
      recorded over 1 year. Symptomatic improvement occurred only with posthypoxic
      myoclonus, which was rapid, dramatic and sustained. All other forms of myoclonus
      either did not improve or worsened (1 essential myoclonus, 2 myoclonus-dystonia,
      2 PME, 2 mitochondrial disease). Levetiracetam has promising but selective
      antimyoclonic potential, which should be the subject of further study.

PMID- 15734677
TI  - Understanding the odd science of aging.
AB  - Evolutionary considerations suggest aging is caused not by active gene
      programming but by evolved limitations in somatic maintenance, resulting in a
      build-up of damage. Ecological factors such as hazard rates and food availability
      influence the trade-offs between investing in growth, reproduction, and somatic
      survival, explaining why species evolved different life spans and why aging rate
      can sometimes be altered, for example, by dietary restriction. To understand the
      cell and molecular basis of aging is to unravel the multiplicity of mechanisms
      causing damage to accumulate and the complex array of systems working to keep
      damage at bay.

PMID- 15734678
TI  - The plasticity of aging: insights from long-lived mutants.
AB  - Mutations in genes affecting endocrine signaling, stress responses, metabolism,
      and telomeres can all increase the life spans of model organisms. These mutations
      have revealed evolutionarily conserved pathways for aging, some of which appear
      to extend life span in response to sensory cues, caloric restriction, or stress.
      Many mutations affecting longevity pathways delay age-related disease, and the
      molecular analysis of these pathways is leading to a mechanistic understanding of
      how these two processes--aging and disease susceptibility--are linked.

PMID- 15734679
TI  - Sex and death: what is the connection?
AB  - A cost of reproduction, where lifespan and fecundity are negatively correlated,
      is of widespread occurrence. Mutations in insulin/IGF signaling (IIS) pathways
      and dietary restriction (DR) can extend lifespan in model organisms but do not
      always reduce fecundity, suggesting that the link between lifespan and fecundity
      is not inevitable. Understanding the molecular basis of the cost of reproduction
      will be informed by elucidation of the mechanisms by which DR and IIS affect
      these two traits.

PMID- 15734680
TI  - Calorie restriction--the SIR2 connection.
AB  - A nutritious diet low in calories improves the health and extends the life span
      of rodents. Recent studies identified a gene, SIR2, which encodes an NAD
      dependent deacetylase and may mediate the effects of calorie restriction. In this
      review, we discuss SIR2 genes and calorie restriction in the lower organisms
      yeast and Drosophila. We then describe the physiological changes in mammals
      during calorie restriction and how they may lead to the observed health benefits.
      We summarize the roles of mammalian Sirt1 in mediating these changes in tissues
      and endocrine systems and propose that Sirt1 regulates calorie restriction by
      sensing low calories and triggering physiological changes linked to health and
      longevity.

PMID- 15734681
TI  - Mitochondria, oxidants, and aging.
AB  - The free radical theory of aging postulates that the production of intracellular
      reactive oxygen species is the major determinant of life span. Numerous cell
      culture, invertebrate, and mammalian models exist that lend support to this half
      century-old hypothesis. Here we review the evidence that both supports and
      conflicts with the free radical theory and examine the growing link between
      mitochondrial metabolism, oxidant formation, and the biology of aging.

PMID- 15734682
TI  - DNA repair, genome stability, and aging.
AB  - Aging can be defined as progressive functional decline and increasing mortality
      over time. Here, we review evidence linking aging to nuclear DNA lesions: DNA
      damage accumulates with age, and DNA repair defects can cause phenotypes
      resembling premature aging. We discuss how cellular DNA damage responses may
      contribute to manifestations of aging. We review Sir2, a factor linking genomic
      stability, metabolism, and aging. We conclude with a general discussion of the
      role of mutant mice in aging research and avenues for future investigation.

PMID- 15734683
TI  - Senescent cells, tumor suppression, and organismal aging: good citizens, bad
      neighbors.
AB  - Cells from organisms with renewable tissues can permanently withdraw from the
      cell cycle in response to diverse stress, including dysfunctional telomeres, DNA
      damage, strong mitogenic signals, and disrupted chromatin. This response, termed
      cellular senescence, is controlled by the p53 and RB tumor suppressor proteins
      and constitutes a potent anticancer mechanism. Nonetheless, senescent cells
      acquire phenotypic changes that may contribute to aging and certain age-related
      diseases, including late-life cancer. Thus, the senescence response may be
      antagonistically pleiotropic, promoting early-life survival by curtailing the
      development of cancer but eventually limiting longevity as dysfunctional
      senescent cells accumulate.

PMID- 15734684
TI  - Genetic modulation of senescent phenotypes in Homo sapiens.
AB  - Single-gene mutations can produce human progeroid syndromes--phenotypes that
      mimic usual or "normative" aging. These can be divided into two classes--those
      that have their impacts upon multiple organs and tissues (segmental progeroid
      syndromes) and those that have their major impacts upon a single organ or tissue
      (unimodal progeroid syndromes). The prototypic example of the former is the
      Werner syndrome, a condition caused by mutations of the RecQ family of DNA
      helicases. Research on the Werner syndrome and a surprising number of other
      progeroid syndromes support the importance of the maintenance of genomic
      stability as a partial antidote to aging. The prototypic examples of the latter
      are Alzheimer type dementias. The three gene products that cause rare autosomal
      dominant early-onset varieties of these disorders all participate in the
      modulation of the beta amyloid precursor protein. They thus support the
      importance of the maintenance of proper protein processing and folding as a
      partial antidote to aging.

PMID- 15734685
TI  - Longevity and lineages: toward the integrative biology of degenerative diseases
      in heart, muscle, and bone.
AB  - Human aging is characterized by debilitating diseases, including heart failure,
      cardiac pacemaker defects, muscle wasting, and osteoporosis, in heart, skeletal
      muscle, and bone. Recent studies are identifying pathways for these aging-related
      diseases by examining how the process of aging influences tissue-specific
      progenitors and differentiated cell lineages in these organ systems. These
      advances form a foundation for new therapeutic strategies to delay the onset of
      aging-related disorders.

PMID- 15734686
TI  - Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic
      perspective.
AB  - From Alois Alzheimer's description of Auguste D.'s brain in 1907 to George
      Glenner's biochemical dissection of beta-amyloid in 1984, the "amyloid
      hypothesis" of Alzheimer's disease has continued to gain support over the past
      two decades, particularly from genetic studies. Here we assess the amyloid
      hypothesis based on both known and putative Alzheimer's disease genes.

PMID- 15734687
TI  - The future of aging therapies.
AB  - Advances in understanding aging processes and their consequences are leading to
      the development of therapies to slow or reverse adverse changes formerly
      considered to be "normal" aging and processes that underlie multiple age-related
      conditions. Estimating the effectiveness of candidate aging therapies, whose
      effects on human aging may require many years to determine, is a particular
      challenge. Strategies for identifying candidate interventions can be developed
      through multiple approaches, including the screening of molecular targets and
      pathways in vitro and in animal models, informed as well by evidence from human
      genetic and epidemiologic data. A number of recently established programs and
      networks can serve as resources for such research. For all these research
      approaches, from in vitro molecular studies to clinical trials, contributions of
      cell and molecular biology are crucial and offer the prospect of therapeutic
      advances that address fundamental biological processes as well as the clinically
      important challenges of aging.

PMID- 15734688
TI  - Menstrual cycle, pregnancy and oral contraceptive use alter attraction to
      apparent health in faces.
AB  - Previous studies demonstrating changes in women's face preferences have
      emphasized increased attraction to cues to possible indirect benefits (e.g.
      heritable immunity to infection) that coincides with periods of high fertility
      (e.g. the late follicular phase of the menstrual cycle). By contrast, here we
      show that when choosing between composite faces with raised or lowered apparent
      health, women's preferences for faces that are perceived as healthy are (i)
      stronger during the luteal phase of the menstrual cycle than during the late
      follicular, fertile phase, (ii) stronger in pregnant women than in non-pregnant
      women and (iii) stronger in women using oral contraceptives than in women with
      natural menstrual cycles. Change in preference for male faces was greater for
      short- than long-term relationships. These findings indicate raised progesterone
      level is associated with increased attraction to facial cues associated with
      possible direct benefits (e.g. low risk of infection) and suggest that women's
      face preferences are influenced by adaptations that compensate for weakened
      immune system responses during pregnancy and reduce the risk of infection
      disrupting foetal development.

PMID- 15734689
TI  - Ascent exhalations of Antarctic fur seals: a behavioural adaptation for breath
      hold diving?
AB  - Novel observations collected from video, acoustic and conductivity sensors showed
      that Antarctic fur seals consistently exhale during the last 50-85% of ascent
      from all dives (10-160 m, n > 8000 dives from 50 seals). The depth of initial
      bubble emission was best predicted by maximum dive depth, suggesting an
      underlying physical mechanism. Bubble sound intensity recorded from one seal
      followed predictions of a simple model based on venting expanding lung air with
      decreasing pressure. Comparison of air release between dives, together with lack
      of variation in intensity of thrusting movement during initial descent regardless
      of ultimate dive depth, suggested that inhaled diving lung volume was constant
      for all dives. The thrusting intensity in the final phase of ascent was greater
      for dives in which ascent exhalation began at a greater depth, suggesting an
      energetic cost to this behaviour, probably as a result of loss of buoyancy from
      reduced lung volume. These results suggest that fur seals descend with full lung
      air stores, and thus face the physiological consequences of pressure at depth. We
      suggest that these regular and predictable ascent exhalations could function to
      reduce the potential for a precipitous drop in blood oxygen that would result in
      shallow-water blackout.

PMID- 15734690
TI  - Male mate choice influences female promiscuity in Soay sheep.
AB  - In most animal species, males are predicted to compete for reproductive
      opportunities, while females are expected to choose between potential mates.
      However, when males' rate of reproduction is constrained, or females vary widely
      in 'quality', male mate choice is also predicted to occur. Such conditions exist
      in the promiscuous mating system of feral Soay sheep on St Kilda, Scotland, where
      a highly synchronized mating season, intense sperm competition and limitations on
      sperm production constrain males' potential reproductive rate, and females vary
      substantially in their ability to produce successful offspring. We show that,
      consistent with predictions, competitive rams focus their mating activity and
      siring success towards heavier females with higher inclusive fitness. To our
      knowledge, this is the first time that male mate choice has been identified and
      shown to lead to assortative patterns of parentage in a natural mammalian system,
      and occurs despite fierce male-male competition for mates. An additional
      consequence of assortative mating in this population is that lighter females
      experience a series of unstable consorts with less adept rams, and hence are
      mated by a greater number of males during their oestrus. We have thus also
      identified a novel male-driven mechanism that generates variation in female
      promiscuity, which suggests that the high levels of female promiscuity in this
      system are not part of an adaptive female tactic to intensify post-copulatory
      competition between males.

PMID- 15734691
TI  - Successful sons or superior daughters: sex-ratio variation in springbok.
AB  - Mothers would often benefit from producing more offspring of one sex than the
      other. Although some species show an astonishing ability to skew their sex ratio
      adaptively, the trends found in many studies on vertebrates have proved
      inconsistent. Furthermore, evidence for a mechanism by which such a bias is
      achieved is equivocal at best. Here, we examine sex-ratio variation over 30
      years, both at an individual and a population level, in the highly polygynous,
      size-dimorphic springbok (Antidorcas marsupialis). Many previous studies of
      similar species have shown that mothers in superior condition preferentially
      produce sons, whereas those in poorer condition produce more daughters. We found
      the opposite to be true in springbok, perhaps because daughters provide mothers
      in superior condition with a more rapid and secure fitness return. This theory
      was supported by the findings that earlier-conceived offspring tended to be
      female and that an increased proportion of daughters were produced with
      increasing rainfall (which was likely to reduce nutritional stress). We also show
      that selective reabsorption of embryos is unlikely to be the main mechanism by
      which deviations from an equal sex ratio are achieved. Hence, either differential
      implantation occurs or females are able to influence the sex of the sperm
      fertilizing an egg.

PMID- 15734692
TI  - Playback of colony sound alters the breeding schedule and clutch size in zebra
      finch (Taeniopygia guttata) colonies.
AB  - The hypothesis that social stimulation, derived from the presence and activities
      of conspecifics, can hasten and synchronize breeding in colonies of birds was
      tested. A modified playback/recorder system was used to continuously exaggerate
      the amount of colony sound available to zebra finches throughout their courtship
      period. Males that heard 'sound supplements' generated from their own colony sang
      more than males in control colonies that did not receive playback; males that
      heard samples from a different colony, sang at an intermediate level. Females
      that were exposed to the vocalizations of their mate and playback from a colony
      other than their own, laid eggs earlier and more synchronously than females in
      control colonies. Females that heard the vocalizations of their mate along with
      playback samples generated from their own colony, laid eggs more synchronously
      but not earlier than control females. Both acoustic treatments caused females to
      lay larger clutches. Social stimulation influences the breeding schedule and
      clutch size in zebra finch colonies. If there are advantages associated with
      these effects, social stimulation may contribute to the maintenance of colonial
      breeding systems.

PMID- 15734693
TI  - Co-infection of Mycobacterium tuberculosis and Mycobacterium leprae in human
      archaeological samples: a possible explanation for the historical decline of
      leprosy.
AB  - Both leprosy and tuberculosis were prevalent in Europe during the first
      millennium but thereafter leprosy declined. It is not known why this occurred,
      but one suggestion is that cross-immunity protected tuberculosis patients from
      leprosy. To investigate any relationship between the two diseases, selected
      archaeological samples, dating from the Roman period to the thirteenth century,
      were examined for both Mycobacterium leprae and Mycobacterium tuberculosis DNA,
      using PCR. The work was carried out and verified in geographically separate and
      independent laboratories. Several specimens with palaeopathological signs of
      leprosy were found to contain DNA from both pathogens, indicating that these
      diseases coexisted in the past. We suggest that the immunological changes found
      in multi-bacillary leprosy, in association with the socio-economic impact on
      those suffering from the disease, led to increased mortality from tuberculosis
      and therefore to the historical decline in leprosy.

PMID- 15734694
TI  - Pancrustacean phylogeny: hexapods are terrestrial crustaceans and maxillopods are
      not monophyletic.
AB  - Recent molecular analyses indicate that crustaceans and hexapods form a clade
      (Pancrustacea or Tetraconata), but relationships among its constituent lineages,
      including monophyly of crustaceans, are controversial. Our phylogenetic analysis
      of three protein-coding nuclear genes from 62 arthropods and lobopods
      (Onychophora and Tardigrada) demonstrates that Hexapoda is most closely related
      to the crustaceans Branchiopoda (fairy shrimp, water fleas, etc.) and
      Cephalocarida + Remipedia, thereby making hexapods terrestrial crustaceans and
      the traditionally defined Crustacea paraphyletic. Additional findings are that
      Malacostraca (crabs, isopods, etc.) unites with Cirripedia (barnacles, etc.) and
      they, in turn, with Copepoda, making the traditional crustacean class Maxillopoda
      paraphyletic. Ostracoda (seed shrimp)--either all or a subgroup--is associated
      with Branchiura (fish lice) and likely to be basal to all other pancrustaceans. A
      Bayesian statistical (non-clock) estimate of divergence times suggests a
      Precambrian origin for Pancrustacea (600 Myr ago or more), which precedes the
      first unambiguous arthropod fossils by over 60 Myr.

PMID- 15734695
TI  - Selection for plasmid post-segregational killing depends on multiple infection:
      evidence for the selection of more virulent parasites through parasite-level
      competition.
AB  - Is the virulence of parasites an outcome of optimized infection? Virulence has
      often been considered an inevitable consequence of parasite reproduction when the
      cost incurred by the parasite in reducing the fitness of its current host is
      offset by increased infection of new hosts. More recent models have focused on
      how competition occurring between parasites during co-infection might effect
      selection of virulence. For example, if co-infection was common, parasites with
      higher intrinsic growth rates might be selected, even at the expense of being
      optimally adapted to infect new hosts. If growth rate is positively correlated
      with virulence, then competition would select increased virulence. We tested
      these models using a plasmid-encoded virulence determinant. The virulence
      determinant did not contribute to the plasmid's reproduction within or between
      hosts. Despite this, virulent plasmids were more successful than avirulent
      derivatives during selection in an environment allowing within-host competition.
      To explain these findings we propose and test a model in which virulent parasites
      are selected by reducing the reproduction of competitors.

PMID- 15734696
TI  - The invasive Korea and Japan types of Varroa destructor, ectoparasitic mites of
      the Western honeybee (Apis mellifera), are two partly isolated clones.
AB  - Varroa destructor, now a major pest of the Western honeybee, Apis mellifera,
      switched from its original host, the Eastern honeybee, A. cerana, ca. 50 years
      ago. So far, only two out of several known mitochondrial haplotypes of V.
      destructor have been found to be capable of reproducing on A. mellifera (Korea
      and Japan). These haplotypes are associated in almost complete cytonuclear
      disequilibrium to diagnostic alleles at 11 microsatellite loci. By contrast,
      microsatellite polymorphism within each type is virtually absent, because of a
      severe bottleneck at the time of host change. Accordingly, 12 mitochondrial
      sequences of 5185 nucleotides displayed 0.40% of nucleotide divergence between
      haplotypes and no intra haplotype variation. Hence, each type has a quasi-clonal
      structure. The nascent intratype variability is subsequent to the clone formation
      50 years ago: in both types the variant alleles differ from the most common by
      one (in 10 cases), two (five cases) or three (one case) repeated motifs. In
      addition to individuals of the two 'pure' types, five F1 hybrids and 19
      recombinant individuals (Japan alleles introgressed into the Korea genetic
      background) were detected. The existence of F1 and recombinant individuals in
      admixed populations requires that double infestations of honeybee cells occur in
      a high proportion but the persistence of pure types suggests a post-zygotic
      isolation between the two clones.

PMID- 15734697
TI  - Convergent incidences of Wolbachia infection in fig wasp communities from two
      continents.
AB  - Wide surveys suggest that Wolbachia bacteria infect ca. 20% of all insect
      species, but particular taxonomic or ecological groups may display significantly
      higher or lower incidences. We studied 61 fig wasp species in Australia and found
      the highest known incidence (67%) of infection in a targeted study of this
      nature. A comparable study in Panama reported a similar figure (59%), confirming
      the exceptionally high incidence of Wolbachia in fig wasps. Importantly, these
      are two independent estimates of Wolbachia incidence in fig wasp communities,
      because no host species, or even genera, are shared between localities. The high
      level of infection may reflect enhanced opportunities for horizontal transmission
      inside fig fruits. Although incidence was similar in Panama and Australia, the
      actual strains involved were different and region-specific. Local strains were
      shared by several host species, although there was often no obvious (direct)
      ecological link between two hosts with the same infection.

PMID- 15734698
TI  - Aposematism: what should our starting point be?
AB  - The evolution of aposematism is considered to be a major evolutionary problem
      because if new aposematic forms emerged in defended cryptic populations, they
      would face the dual problems of rarity and conspicuousness. We argue that this
      commonly assumed starting point might not have wide validity. We describe a novel
      evolutionary computer model in which prey evolve secondary defences and become
      conspicuous by moving widely over a visually heterogeneous habitat. Unless
      crypsis imposes high opportunity costs (for instance, preventing prey from
      efficient foraging, thermoregulation and communication), costly secondary
      defences are not predicted to evolve at all. However, when crypsis imposes
      opportunity costs, prey evolve secondary defences that facilitate raised
      behavioural conspicuousness as prey exploit opportunities within their
      environment. Optimal levels of secondary defence and of behavioural
      conspicuousness increase with population sizes and the costs imposed by crypsis.
      When prey are already conspicuous by virtue of their behaviours, the evolution of
      aposematic appearances (bright coloration, etc.) is much easier to explain
      because aposematic traits add little further costs of conspicuousness, but can
      bring large benefits.

PMID- 15734699
TI  - Discrete hierarchical organization of social group sizes.
AB  - The 'social brain hypothesis' for the evolution of large brains in primates has
      led to evidence for the coevolution of neocortical size and social group sizes,
      suggesting that there is a cognitive constraint on group size that depends, in
      some way, on the volume of neural material available for processing and
      synthesizing information on social relationships. More recently, work on both
      human and non-human primates has suggested that social groups are often
      hierarchically structured. We combine data on human grouping patterns in a
      comprehensive and systematic study. Using fractal analysis, we identify, with
      high statistical confidence, a discrete hierarchy of group sizes with a preferred
      scaling ratio close to three: rather than a single or a continuous spectrum of
      group sizes, humans spontaneously form groups of preferred sizes organized in a
      geometrical series approximating 3-5, 9-15, 30-45, etc. Such discrete scale
      invariance could be related to that identified in signatures of herding behaviour
      in financial markets and might reflect a hierarchical processing of social
      nearness by human brains.

PMID- 15734700
TI  - Unrelated helpers will not fully compensate for costs imposed on breeders when
      they pay to stay.
AB  - Unrelated subordinates may invest in costly help to avoid being evicted from
      groups (the 'pay-to-stay' hypothesis). However, the effectiveness of eviction to
      enforce help should depend on its being applied accurately and on the costs it
      imposes on both dominants and subordinates. The relative cost of being evicted is
      a function of the population frequency of eviction when population growth is
      limited by density-dependent factors. We describe a stage-structured pay-to-stay
      model incorporating density-dependent population growth, costly eviction and
      occasional errors. Breeders demand some amount of help and evict subordinates
      that do not provide it. Helpers decide on the amount of help they will provide.
      The threat of eviction alone is sufficient to enforce helping. However, helping
      will not be favoured if helpers do not impose costs on breeders. The amount of
      help provided is less than the cost that subordinates impose upon breeders, when
      any help is provided. Thus, the net fitness effect of a helper under pay-to-stay
      alone is negative, even if it is investing in cooperative behaviour. Constraints
      on dispersal have no effect on the amount of help, although they may influence
      the tolerance threshold of breeders and group stability, depending on the
      mechanism of density dependence.

PMID- 15734701
TI  - Origin of the endemic fern genus Diellia coincides with the renewal of Hawaiian
      terrestrial life in the Miocene.
AB  - The enigmatic fern genus Diellia, endemic to the Hawaiian archipelago, consists
      of five extant and one recently extinct species. Diellia is morphologically
      highly variable, and a unique combination of characters has led to several
      contrasting hypotheses regarding the relationship of Diellia to other ferns. A
      phylogenetic analysis of four chloroplast loci places Diellia within 'black
      stemmed' rock spleenworts of the species-rich genus Asplenium, as previously
      suggested by W. H. Wagner. Using an external calibration point, we estimate the
      divergence of the Diellia lineage from its nearest relatives to have occurred at
      ca. 24.3 Myr ago matching an independent estimate for the renewal of Hawaiian
      terrestrial life (ca. 23 Myr ago). We therefore suggest that the ancestor of the
      Diellia lineage may have been among the first successful colonists of the newly
      emerging islands in the archipelago. Disparity between morphological and
      nucleotide sequence variation within Diellia is consistent with a recent rapid
      radiation. Our estimated time of the Diellia radiation (ca. 2 Myr ago) is younger
      than the oldest island of Kaua'i (ca. 5.1 Myr ago) but older than the younger
      major islands of Maui (ca. 1.3 Myr ago), Lana'i (ca. 1.3 Myr ago) and Hawaii (ca.
      0.43 Myr ago).

PMID- 15734703
TI  - Food and nutrient intakes among nomads living in three different areas of Inner
      Mongolia, China.
AB  - The subjects, from Mongolian-style gel tribes, aged 6-79 years, living in three
      different areas of Inner Mongolia, were asked about their daily food consumption
      in August 2001 using the 24-hr dietary recall method. There were no significant
      differences in food intakes between males and females of the same age group in
      the same area, with a few exceptions, although considerable variation was found
      among individuals and areas for the amount of foods consumed. Some subjects
      consumed greater amounts of wheat, vegetables, fruits, and vegetable oils, which
      suggested they had changed their eating patterns. All subjects drank large
      quantities of tea, to which was added milk (sheep/goat), cream, butter, parched
      millet and/or sawa. This traditional tea supplied vitamins and minerals such as
      vitamin A, iron and calcium.

PMID- 15734702
TI  - Does diet matter for survival in long-lived cultures?
AB  - In 1987, the International Union of Nutritional Sciences (IUNS) subcommittee on
      Nutrition and Ageing, in conjunction with the World Health Organization (WHO)
      global program for the elderly, embarked on the 'Food Habits in Later Life'
      (FHILL): a cross-cultural study to determine to what extent health, social and
      lifestyle variables, especially food intake, collectively predict survival
      amongst long-lived cultures. A total of 818 participants aged 70 years and over
      were recruited from five IUNS centres. Mortality data were collected after five
      to seven years. The cohorts included Swedes in Sweden (SWD), Greeks in Greece
      (GRS) and in Melbourne, Australia (GRM), Anglo-Celts in Australia (ACS) and
      Japanese in Japan (JPN). Information was obtained on health, lifestyle and diet
      at baseline. A Cox Proportional Hazard model containing ten potential predictors
      of survival, adjusted to age at enrollment and ethnicity/locality, was developed
      to analyse the survival data. Based on up to seven years survival data, it was
      found that being an elderly Greek in Australia conferred the lowest mortality
      risk and being an elderly Greek in Greece conferred the highest mortality risk.
      When the ten potential predictors of survival were entered into the Cox model,
      the memory score, the Mediterranean diet score, Activities of Daily Living (ADL)
      and general health status scores showed the greatest effects in significantly
      reducing mortality hazard ratios by 22%, 13%, 4% and 4%, respectively. For diet
      score, a one-unit change predicted a significant 13% difference in survival. Of
      the lifestyle (modifiable) variables entered in the multivariate model, exercise
      and social activity were not significant predictors of survival suggesting that
      diet is a more important predictor of survival than these variables. Another
      lifestyle variable, smoking, significantly increased mortality hazard ratios by
      67%, making it a more important predictor of survival than diet. Being male (non
      modifiable) also increased risk of death by 63%. Diet, particularly the
      Mediterranean Diet, operates irrespective and together with other factors as an
      appreciable contributor to survival, with a strength comparable to or greater
      than all other measured variables. The independence and strength of the
      predictiveness of food pattern for survival, and for this to be cross-cultural
      from Europe to Asia is a novel and important observation for food and health
      policy.

PMID- 15734704
TI  - Physical status, nutrient intake and dietary pattern of adolescent female factory
      workers in urban Bangladesh.
AB  - This cross-sectional study examined the physical status, nutrient intake and
      dietary pattern of adolescent female factory workers in urban Bangladesh. A total
      of 1211 postmenarchial girls aged 14-19 y from seventeen readymade garment
      industries spread over the Dhaka City participated in the study. Body weight,
      height and skin fold thickness were measured for all subjects. The nutrient
      intake was assessed by 24-h recall method and 7-day food frequency questionnaire
      was used to investigate their dietary pattern on a sub-sample of 509 girls. Sixty
      five percent of the girls were short (height-for-age, <3rd percentile of NCHS
      reference values). Pre-valence of short stature was higher in the older girls.
      Mean body weight was 38k g for the 14 year old girls, which gradually increased
      across the age groups to about 42 kg for the 18 and 19 year olds. About 17% of
      the girls were thin (BMI-for-age <5th percentile of NCHS reference values). Over
      all, about 23% were lean (TSFT-for-age <5th percentile of NCHS reference values).
      Food intake data revealed a deficit of 1.62 MJ/day in energy. Mean intake of
      protein, calcium, iron, vitamin A, thiamin, riboflavin, niacin and vitamin C were
      below the recommended dietary allowance. Most of the energy and nutrients came
      from cereal grains. Habitual pattern of food intake revealed poor intake of eggs,
      milk, meat, and green leafy vegetables. In conclusion, the data show a poor
      physical status of the adolescent female factory workers in Bangladesh.
      Simultaneous substantial deficits in energy and several nutrients in their diet
      stress the need for an appropriate intervention to improve their overall
      nutritional and physical status of these young females.

PMID- 15734705
TI  - Iodine status in pregnant women living in Melbourne differs by ethnic group.
AB  - The iodine status of pregnant women from different ethnic groups in an Australian
      population was determined by measuring urinary iodine concentration (UIC) from
      stored spot urine samples. Study subjects were selected from pregnant women
      participating in a Down Syndrome screening study at Monash Medical Centre in
      Melbourne, Australia. In total, 263 Vietnamese, 262 Indian/Sri Lankan (ISL) and
      277 Caucasian women were included. The median UIC of Caucasian women (52
      microg/L) was significantly lower than that of both Vietnamese women (58
      microg/L, P <0.01) and ISL women (61 microg/L, P = 0.03). The proportion of women
      who had a UIC below 50 microg/L was 48.4% of the Caucasian women, 38.4% of the
      Vietnamese women and 40.8% of the ISL women. These data are consistent with mild
      iodine deficiency for each of the groups of pregnant women. The evidence for mild
      iodine deficiency in these groups of pregnant women is consistent with recent
      Australian studies in pregnant and non-pregnant individuals. The association of
      ethnicity with iodine status is most likely due to differences in dietary
      behaviours. Understanding the factors that influence iodine nutrition in a
      multiethnic population will be important for identifying the most useful
      approaches to improving iodine status, evaluating different strategies and the
      development of appropriate monitoring programs. Action to improve iodine status
      in the Australian population should include consideration of ethnic differences
      in diet.

PMID- 15734706
TI  - The effects of iodine on intelligence in children: a meta-analysis of studies
      conducted in China.
AB  - This study quantifies the effects of iodine on the intellectual development of
      children using a systematic manual literature search of Chinese publications
      related to iodine deficiency disorders. The Chinese Medical Reference Database,
      Medline, and Cochrane library were searched electronically in Chinese and
      English. Inclusion criteria included: studies conducted in China, comparing
      children (<16 ys) living in naturally iodine sufficient (IS) with those in
      severely iodine deficient (ID) areas, or children in ID areas born before and
      after the introduction of iodine supplementation. Intelligent Quotient (IQ) was
      measured using Binet or Raven Scales. The iodine sufficient control groups were
      comparable socially, economically, and educationally with the study groups.
      Random effects models were used in the meta-analysis. Effect size was the
      standard deviation IQ point (SIQP), which is equivalent to 15 IQ. Thirty-seven
      reported studies, total 12,291 children, were analysed. The effect size was an
      increase of 0.83, 0.82, and 0.32 SIQP respectively, for the children living in IS
      communities compared with those living in ID areas with no iodine
      supplementation, with inadequate iodine supplementation, or children who had
      received iodine during their mothers' pregnancy and after birth. These equal to
      12.45, 12.3, 4.8 IQ points. Compared with that of children whose mothers were
      persistently exposed to ID, the total effect size of the 21 entries was an
      increase of 0.58 SIQP (8.7 IQ points) in the group receiving iodine
      supplementation during pregnancy. Furthermore, there was an increase on 1.15 SIQP
      of Binet or 0.8 SIQP on Raven Scale (17.25 or 12 IQ points) for children born
      more than 3.5 years after iodine supplementation program was introduced. The
      level of iodine nutrition plays a crucial role in the intellectual development of
      children. The intelligence damage of children exposed to severe ID was profound,
      demonstrated by 12.45 IQ points loss and they recovered 8.7 IQ points with iodine
      supplementation or IS before and during pregnancy. Iodine supplementation before
      and during pregnancy to women living in severe ID areas could prevent their
      children from intelligence deficit. This effect becomes evident in children born
      3.5 years after the iodine supplementation program was introduced.

PMID- 15734707
TI  - The effect of vitamin A-fortified coconut cooking oil on the serum retinol
      concentration of Filipino children 4-7 years old.
AB  - A 6-month intervention trial was conducted among 542 Filipino children aged 4 to
      7 years to determine the effect of vitamin A-fortified coconut cooking oil intake
      on their vitamin A status and to identify factors that influence this. Children
      were randomly assigned to the Experimental group, with vitamin A-fortified
      cooking oil ration; to Control-1 group with unfortified cooking oil ration; and
      to Control-2 group without cooking oil ration. In all groups, children's serum
      retinol concentration improved. Relative change in serum retinol concentration
      was significantly higher among the Experimental group, with one-third of total
      vitamin A intake coming from vitamin A-fortified cooking oil intake, than in the
      Control groups, with more than half of intake from other vitamin A-rich foods.
      Determinants of post-intervention serum retinol concentration included baseline
      serum retinol concentration, caregiver's education, receipt of high-dose vitamin
      A capsule, interaction between consumption of vitamin A-fortified cooking oil and
      of other vitamin A-rich foods, and between households purchasing cooking oil and
      food expenditure. Intake of vitamin A-fortified cooking oil combined with vitamin
      A-rich foods was necessary to increase serum retinol concentration. It is
      recommended to vigorously promote the consumption of vitamin A-fortified cooking
      oil together with other vitamin A-rich sources to sustain the prevention and
      control of vitamin A deficiency.

PMID- 15734708
TI  - Correlates of under- and over-reporting of energy intake in Tehranians: body mass
      index and lifestyle-related factors.
AB  - Under- and over-reporting of energy intake are problems in dietary intake
      assessment. This study was conducted to assess the correlates of under- and over
      reporting of energy intake in Tehranians. Dietary data on 947 participants (415
      males and 532 females) of the Tehran Lipid and Glucose Study was collected by
      trained interviewers using two 24-hour recalls. Weight and height were measured
      by digital scale and tape measure according to standard protocols and recorded to
      the nearest 100 g and 1cm, respectively. Under-, normal- and over-reporting of
      energy intake was defined as ratio of energy intake to basal metabolic rate
      (EI:BMR) <1.35, 1.35-2.39 and >or = 2.4, respectively. Mean +/- SD of age was
      37.3 +/-14.6 and 32.9 +/-13.6 years for men and women, respectively. Men had
      higher EI:BMR than women (1.72 +/-0.44 vs 1.27 +/-0.44, P<0.001). EI and EI:BMR
      was highest in the youngest age groups in both sexes. The prevalences of under-
      and over-reporting were 31% and 5%, respectively. Fewer men than women
      underreported EI (19% vs 40%, P<0.001). The fraction of over-reporters was
      significantly higher in men than women (7% vs 3%, P<0.05). EI:BMR decreased with
      age. Under-reporters were older and had higher BMI than normal-reporters, but
      their educational level did not differ significantly. Over-reporters were younger
      and had lower BMI than normal-reporters, but their educational levels did not
      differ significantly. Most over-reporters had normal BMI. Smoking was more
      prevalent in over-reporters than in the normal-reporters (28% vs 19% in men and
      6% vs 1% in women, P<0.01). The results showed a high prevalence of misreporting
      of energy intake in Tehran. This phenomenon is related to age, obesity and
      smoking habits.

PMID- 15734709
TI  - Waist girth normalized to body build in obesity assessment.
AB  - Waist girth (WG) is regarded as the most significant anthropometric parameter
      associated with cardiovascular risk. The objective of the present study was to
      strengthen WG as an obesity marker by basing WG assessment not on gender but on
      individually measured body build characteristics that need not coincide with
      gender. We formulated a new marker, the Waist Reference Girth (WRG) and two
      corollaries, the Waist Deviation (WD) and the Percent Waist Deviation (%WD). The
      present research centered on deriving an equation for WRG from relevant trunk
      skeletal measurements that closely predicted WG in lean individuals. This
      equation would determine any individual's WRG and current WD. Trunk skeletal
      widths and chest depth as well as WG were measured on 507 physically active
      subjects (247 men and 260 women), predominantly lean young adults. Multiple
      regression analysis with the skeletal measurements as independent variables was
      performed on this data to predict WG. The unisex WRG equation WRG = Chest Sum x
      1.635 predicted WG of 282 lean subjects (maximum WD of 4 cm) with R(2) of 0.87
      (SEE of 3.0 cm). Male and female WG cutoff values for central obesity are usually
      taken at 94 cm and 80 cm respectively. For the average male and female WRG in
      this study (79 cm and 67.4 cm), these cutoff values are equivalent to WD of 15 cm
      and 12.6 cm respectively and to 19%WD for both genders (15/79 and 12.6/67.4).
      With %WD normalized for WRG, hence unaffected by intra-group or inter-group
      variations in the Chest Sum, %WD thresholds may better identify health risks
      linked to abdominal obesity than existing WG thresholds.

PMID- 15734710
TI  - Increased abdominal fat in young women of Indian origin.
AB  - People of Indian origin develop type 2 diabetes at a relatively young age and low
      body mass index compared to people of other racial groups, possibly because of
      preferential accumulation of abdominal fat. We examined the relationship between
      abdominal fat and body mass index (BMI) in healthy premenopausal women of
      different racial groups, and compared abdominal fat measurements at different
      ages. Women of Chinese, European, Indian or Polynesian origin (50 of each, mean
      age 31) had dual energy x-ray absorptiometry of the lumbar spine, with estimation
      of the percentage fat in the abdominal area. Polynesian women had a significantly
      greater mean BMI (P< 0.001) than all other groups, and a higher abdominal fat
      than European and Chinese woman (P< 0.001). Although the Indian women had a
      similar mean BMI to the European and Chinese women, they had a significantly
      greater abdominal fat (P<0.001). When examined by age tertile, the Indian women
      had significantly more abdominal fat than Chinese or European women at all ages
      (P<0.001), with marked differences evident even in the youngest group (mean age
      23 years). Compared to other racial groups, women of Indian origin preferentially
      accumulate abdominal fat--a trait that is well established in young adulthood.

PMID- 15734711
TI  - Anthropometric indices as screening tools for cardiovascular risk factors in
      Singaporean women.
AB  - Previous studies have suggested the need to revise the World Health Organization
      (WHO) cut-off values for the various indices of obesity and fat distribution in
      Singapore. The purpose of this study was to delineate cut-off points of body mass
      index (BMI), waist-hip ratio (WHR), waist circumference (WC), and waist-stature
      ratio (WSR) as screening tools for cardiovascular risk factors in Singaporean
      women. Anthropometric indices were measured in a cross sectional survey of 566
      subjects (60% Chinese individuals, 28% Malay individuals and 12% Indian
      individuals). Cardiovascular risk factors were determined by measuring blood
      pressure, serum lipids, and fasting blood glucose levels. Receiver Operating
      Characteristic (ROC) curves were constructed to determine cut-off points. Forward
      logistic regression and area under curves (AUC) were used to determine the best
      anthropometric index. For at least one cardiovascular risk factor (hypertension,
      dyslipidaemia and diabetes mellitus), the cut-off points for BMI, WHR, WC and WSR
      were around 23.6 kg/m(2), 0.80, 77.8 cm and 0.48 for Singaporean females. The AUC
      of WSR was the highest for all three risk factors in females (0.79 for
      hypertension, 0.70 for dyslipidaemia, 0.88 for diabetes mellitus). Regression
      analyses revealed that WSR was independently associated with all risk factors.
      For Singaporean female adults, the cut-off points were lower than the criteria
      suggested by the WHO, but were in agreement with those reported for Asians. BMI,
      WHR, WC and WSR may be used as screening tools for cardiovascular risk factors,
      of which WSR may be the best anthropometric index.

PMID- 15734712
TI  - Anthropometric characteristics and nutritional status based on body mass index of
      adult Bathudis: a tribal population of Keonjhar District, Orissa, India.
AB  - A cross-sectional study was undertaken to determine anthropometric profile and
      nutritional status based on body mass index (BMI) of adult Bathudis, a tribal
      population of Orissa, India. A total of 409 adult (aged >18 years) Bathudis of
      three villages of Anandapur, Keonjhar District, Orissa, India, were studied.
      Anthropometric measurements including height, weight, circumferences and
      skinfolds as well as BMI and waist-hip ratio (WHR) were measured. Overall, the
      extent of undernutrition (BMI < 18.5) was found to be very high (57.9%).
      Moreover, there was a significant (chi(2)= 8.09674, P = 0.01745) difference in
      the prevalence of undernutrition between men (52.7%) and women (64.5%). In
      conclusion, this study demonstrated that the prevalence of adult undernutrition
      was found to be very high among the Bathudis, a tribal population of Keonjhar
      District, Orissa. These rates were much higher than those found in several tribal
      populations from other parts of India. Therefore, immediate nutritional
      intervention programs are needed for implementation among Bathudis. Moreover,
      further research is needed not only among this ethnic group but also other tribal
      populations of India to fully understand the causes and consequences of adult
      undernutrition.

PMID- 15734714
TI  - Australian sweet lupin flour addition reduces the glycaemic index of a white
      bread breakfast without affecting palatability in healthy human volunteers.
AB  - The addition of some legume ingredients to bread has been associated with effects
      on glycaemic, insulinaemic and satiety responses that may be beneficial in
      controlling type 2 diabetes, cardiovascular disease and obesity. However, the
      effect of Australian sweet lupin (Lupinus angustifolius) flour (ASLF) is unknown.
      This investigation examined the effect of adding ASLF to standard white bread on
      post-meal glycaemic, insulinaemic and satiety responses and palatability in
      healthy subjects. Using a randomised, single-blind, cross-over design, 11
      subjects consumed one breakfast of ASLF bread and two of standard white bread >
      or =7 days apart after fasting overnight. Each breakfast also included margarine,
      jam, and tea with milk and contained 50 g available carbohydrate. On each test
      day, blood samples were taken after fasting, then several times over 2 hours post
      prandially, and analysed for plasma glucose and serum insulin. Subjects rated
      breakfast palatability and perception of satiety, in the fasting state and over 3
      hours post-prandially, after which food intake from an ad libitum buffet and for
      the rest of the day was recorded. Incremental areas under the curves for glucose,
      insulin and satiety, glycaemic index, insulinaemic index and satiety index were
      calculated. ASLF addition to the breakfast reduced its glycaemic index (mean +/
      SEM; ASLF bread breakfast = 74.0 +/-9.6. Standard white bread breakfast = 100,
      P=0.022), raised its insulinaemic index (ASLF bread breakfast = 127.7 +/-12.0.
      Standard white bread breakfast = 100, P=0.046), but did not affect palatability,
      satiety or food intake. ASLF addition resulted in a palatable breakfast; however,
      the potential benefits of the lowered glycaemic index may be eclipsed by the
      increased insulinaemic index.

PMID- 15734713
TI  - Use of [14C]-sodium bicarbonate/urea to measure physical activity induced
      increases in total energy expenditure in free-living healthy males.
AB  - The aim of this study was to evaluate the utility of the [(14)C]-sodium
      bicarbonate/urea technique to detect physical activity-induced increases in total
      energy expenditure in free-living healthy men. Thirteen healthy males aged 34.1
      +/- 11.7 yrs with body mass index 24.1 +/- 3.1 kg/m(2) were studied on three
      separate occasions, during which [(14)C]-bicarbonate was infused over 48-hours
      and urine was collected during the second 24-hours. On three separate occasions
      and in random order, subjects either remained sedentary, or performed a bout of
      physical activity on an electro-magnetically braked cycle ergometer sufficient to
      increase energy expenditure by 7% or 11% above predicted sedentary total energy
      expenditure. Urine samples were analyzed to evaluate the amount of [(14)C]
      bicarbonate incorporated into urinary urea, thereby reflecting the amount of
      CO(2) produced per day, and upon conversion, the number of kilojoules of energy
      expended in 24-hours. All 13 subjects successfully completed the two physical
      activity treatments and there were no adverse events. As measured by the [(14)C]
      urea assay, mean total energy expenditure values were not significantly different
      between sedentary activity (17902 +/- 905 kJ/day), the physical activity
      treatment designed to increase TEE by 7% (17701 +/- 594 kJ/day) and the physical
      activity treatment designed to increase TEE by 11% (18538 +/- 485 kJ/day)
      (P=0.668). In conclusion, although the [(14)C]-sodium bicarbonate/urea technique
      was well tolerated and did not interfere with normal daily activities, it was not
      able to accurately measure physical activity-induced increases in EE in the range
      of 7-11% above predicted sedentary total energy expenditure.

PMID- 15734715
TI  - Clinical evidence of growth hormone, glutamine and a modified diet for short
      bowel syndrome: meta-analysis of clinical trials.
AB  - This study assessed the safety and efficacy of growth hormone (GH) and glutamine
      (GLN) combined with a modified (high-carbohydrate-low-fat, HCLF) diet in patients
      with short bowel syndrome. A meta-analysis of all the relevant clinical trials
      was performed. Clinical trials were identified from the following electronic
      databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio
      medicine Database. The search was undertaken in May 2004. Language was restricted
      to Chinese and English. Literature references were checked at the same time.
      Clinical trials were extracted and evaluated by two reviewers independently of
      each other. The statistical analysis was performed by RevMan4.2 software which
      was provided by the Cochrane Collaboration. A P value of < 0.05 was considered
      statistically significant. Thirteen trials involving 258 patients were included.
      The combined results showed that GH, GLN and HCLF diet had positive treatment
      effect on body weight (weighted mean difference [WMD] = 2.44, 95%CI [1.62, 3.27],
      P<0.00001), stool output (WMD = -376.49, 95%CI [-600.35, -152.63], P=0.001), lean
      body mass (WMD = 2.16, 95%CI [0.91, 3.41], P=0.0007), absorption of carbohydrates
      (WMD = 6.21, 95%CI [5.27, 7.15], P< 0.00001), absorption of nitrogen (WMD =
      10.83, 95%CI [5.22, 16.44], P=0.0002), absorption of D-xylose (WMD = 0.37, 95%CI
      [0.29, 0.44], P<0.00001), and off TPN (total parenteral nutrition) (odds ratios
      [OR] = 64.63, 95%CI [15.51, 269.22], P<0.00001). But there were no improvements
      in fat mass (WMD = -1.50, 95%CI [-3.48, 0.48], P=0.14), absorption of energy (WMD
      = 7.48, 95%CI [-7.22, 22.17], P=0.32), and absorption of fat (WMD = 7.16, 95%CI [
      2.95, 17.28], P=0.17). Most patients had side effects that are known to occur
      during treatment with high doses (0.14 mg/kg/day) of GH. No serious adverse
      effects occurred during active treatment with low doses (< or =0.1 mg/kg/day) of
      GH. Treatment with a combination of low-dose GH, GLN and HCLF diet is effective
      without any major adverse effects in patients with short bowel syndrome. Further
      trials are required, especially in children, with sufficient size and rigorous
      design.

PMID- 15734716
TI  - Protective effects of bovine colostrum on non-steroidal anti-inflammatory drug
      induced intestinal damage in rats.
AB  - The aim of this study was to examine whether bovine colostrum was able to prevent
      the NSAID induced small intestinal damage in animals. The animal model population
      of the study consisted of 4 groups: control group, diclofenac group, diclofenac
      with 10% low fat milk group and diclofenac with 5% colostrum group. The animals
      with milk or colostrum were fed with 10% low fat milk or 5% colostral solution
      for 5 days before the administration of diclofenac. Gut injuries were induced by
      administration of a single dose of diclofenac (100 mg/kg orally). Epithelial
      permeability values (24 hour urinary excretion of 51Cr-ethylenediaminetetraacetic
      acid [51Cr-EDTA]), enteric aerobic bacterial counts, serum biochemical profiles
      and pathologic findings of distal ileum were measured. Diclofenac caused a marked
      increase in the intestinal permeability, enteric bacterial numbers and intestinal
      villous damage, and enteric protein and albumin loss. Combined administration of
      bovine colostrum reduced the increase in intestinal permeability, enteric
      bacterial overgrowth, protein losing enteropathy and mucosal villous damage of
      the small intestine induced by diclofenac. Bovine colostrum may have a beneficial
      effect in prevention of NSAID induced small intestinal injuries.

PMID- 15734717
TI  - Regulators of G protein signaling & drugs of abuse.
AB  - Drugs of abuse such as opioids and stimulants share a common dopaminergic reward
      pathway; however, in response to continual intermittent exposure to such drugs,
      there are neuronal alterations leading to changes in behavior. Regulators of G
      protein signaling (RGS) are proteins that negatively regulate G protein signaling
      and are expressed in brain areas important for the pharmacology of abused drugs.
      Moreover, the level of expression of several of these proteins is regulated by
      abused drugs. In this article, we discuss RGS proteins, their regulation by
      morphine and stimulants, and how altered levels of these proteins affect cell
      signaling to contribute to the pharmacology and behavioral consequence of abused
      drugs. Finally, we consider if RGS proteins represent viable targets for drug
      abuse medications.

PMID- 15734718
TI  - Orlistat: from antiobesity drug to anticancer agent in Her-2/neu (erbB-2)
      overexpressing gastrointestinal tumors?

PMID- 15734719
TI  - Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance
      to human health.
AB  - The indigenous intestinal microflora are involved in a variety of processes
      within the human body, and are important for maintaining host health. As such,
      interindividual differences in the ability to harbor certain intestinal bacteria
      might be associated with interindividual differences in health and/or disease
      susceptibility. In the last decade there has been considerable interest in
      phytoestrogen intakes in relation to human health. Daidzein, an isoflavone
      phytoestrogen found in soy, is metabolized to equol and O-desmethylangolensin (O
      DMA) by intestinal bacteria. The specific bacterium/bacteria responsible for
      equol and O-DMA production in humans have yet to be identified definitively, but
      in vitro and animal studies have suggested that equol and O-DMA are more
      biologically active than their precursor daidzein. Interestingly, substantial
      interindividual differences in daidzein metabolism exist; following soy or
      daidzein consumption, approximately 30%-50% of the human population produce
      equol, and approximately 80%-90% produce O-DMA. Observational and intervention
      studies in humans have suggested that the ability to produce equol and O-DMA may
      be associated with reduced risk of certain diseases including breast and prostate
      cancers. However, relatively few studies have been conducted to date. In this
      review, we discuss the available evidence for a relationship between
      daidzeinmetabolizing phenotypes and human health, and suggest potential
      mechanisms for some of the reported relationships.

PMID- 15734720
TI  - Physiologically attainable concentrations of lycopene induce mitochondrial
      apoptosis in LNCaP human prostate cancer cells.
AB  - Prostate cancer is the second leading cause of cancer deaths among men in the
      United States. Studies show that people with diets rich in tomato-based foods
      have reduced risks of cancer, viz., prostate cancer. This is attributed, in part,
      to lycopene, the most abundant carotenoid in tomatoes. Thus, we studied the
      effect of lycopene at physiologically attainable concentrations on apoptosis,
      cellular proliferation, and necrosis in LNCaP human prostate cancer cells. Cells
      at 37 degrees C and >80% confluency were treated with media alone (0.32%
      tetrahydrofuran vehicle) or with increasing concentrations (0.3-3.0 microM) of
      lycopene overnight. After washing monolayers, analyses by high-performance liquid
      chromatography (HPLC) showed that cellular accumulation of lycopene was 5.5 +/-
      0.8, 14.0 +/- 3.2, and 36.7 +/- 12.3 pmole/10(6) cells for 0.3, 1.0, and 3.0 muM,
      respectively, and not detected in control cells. Lycopene did not alter cellular
      proliferation because bromodeoxyuridine (BrdU) incorporation and cell numbers
      were identical among groups. However, results of a 3[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide (MTT) assay showed that mitochondrial function
      decreased 61%-83% with increasing concentrations of lycopene (P < 0.001).
      Cytotoxicity and necrosis did not contribute to this effect because lactate
      dehydrogenase (LDH) release (1.5%-1.8%) and trypan blue exclusion (89%-93%) were
      similar. Subsequently, we demonstrated that increasing concentrations of lycopene
      significantly (P < 0.05) reduced mitochondrial transmembrane potential, induced
      the release of mitochondrial cytochrome c, and increased annexin V binding,
      confirming induction of apoptosis. Thus, lycopene at physiologically relevant
      concentrations did not affect cellular proliferation or promote necrosis but
      clearly altered mitochondrial function and induced apoptosis in LNCaP human
      prostate cancer cells.

PMID- 15734721
TI  - A comparison of two exercise training programs on cardiac responsiveness to beta
      stimulation in obesity.
AB  - We demonstrated previously that exercise training did not restore normal cardiac
      beta-adrenergic responsiveness in obese rabbits. This study tested the hypothesis
      that an increased training volume was required to attenuate obesity-related
      reductions in isolated heart responsiveness to isoproterenol. Female New Zealand
      White rabbits were divided into lean control, lean exercise-trained, obese
      control, and obese exercise-trained groups. For the exercise-trained groups,
      total treadmill work over 12 weeks was increased 27% when compared with lean and
      obese animals trained with lower total training volume. After 12 weeks,
      Langendorff isolated hearts were used to study developed pressure, +dP/dt(max),
      and -dP/dt(max) responses to isoproterenol (10(-9) - 3 x 10(-7) M). Concentration
      response data were fit to a sigmoidal function using a four-parameter logistic
      equation. Controls were compared with animals trained under the low- and high
      training volume programs using one-way analysis of variance and Tukey's post-hoc
      test; separate analyses were conducted for lean and obese rabbits. In both lean
      and obese groups trained under the high-training volume program, EC50 values for
      +dP/day(tmax) and -dP/dt(max) were higher compared with same-weight controls and
      animals trained under the low-training volume program, indicating that
      contractility and relaxation responsiveness to isoproterenol was reduced by the
      higher training volume. Therefore, these data indicate that increased training
      volume failed to attenuate obesity-related decrements in isolated heart
      responsiveness to beta-adrenergic stimulation and caused reduced sensitivity to
      isoproterenol in both lean and obese animals.

PMID- 15734722
TI  - Soybean-derived phytoestrogens regulate prostaglandin secretion in endometrium
      during cattle estrous cycle and early pregnancy.
AB  - Phytoestrogens acting as endocrine disruptors may induce various pathologies in
      the female reproductive tract. The purpose of this study was to determine whether
      phytoestrogens present in the soybean and/or their metabolites are detectable in
      the plasma of cows fed a diet rich in soy and whether these phytoestrogens
      influence reproductive efficiency and prostaglandin (PG) synthesis during the
      estrous cycle and early pregnancy in the bovine endometrium. In in vivo
      Experiment 1, we found significant levels of daidzein and genistein in the fodder
      and their metabolites (equol and p-ethyl-phenol) in bovine serum and urine. The
      mean number of artificial inseminations (AIs) and pregnancy rates in two kinds of
      herds, control and experimental (cows fed with soybean 2.5 kg/day), were almost
      double in the soy-diet herd in comparison with the control animals. In in vivo
      Experiment 2, three out of five heifers fed soybean (2.5 kg/day) became pregnant
      whereas four out of five heifers in the control group became pregnant. The
      concentrations of a metabolite of PGF2alpha (PGFM) were significantly higher in
      the blood plasma of heifers fed a diet rich in soybean than those in the control
      heifers throughout the first 21 days after ovulation and AI. The higher levels of
      PGFM were positively correlated with equol and p-ethyl phenol concentrations in
      the blood. In in vitro experiments, the influence of isoflavones on PG secretion
      in different stages of the estrous cycle was studied. Although all phytoestrogens
      augmented the output of both PGs throughout the estrous cycle, equol and p-ethyl
      phenol preferentially stimulated PGF2alpha output. The results obtained lead to
      the conclusion that soy-derived phytoestrogens and their metabolites disrupt
      reproductive efficiency and uterus function by modulating the ratio of PGF2alpha
      to PGE2, which leads to high, nonphysiological production of luteolytic PGF2alpha
      in cattle during the estrous cycle and early pregnancy.

PMID- 15734723
TI  - Acute central infusion of leptin modulates fatty acid mobilization by affecting
      lipolysis and mRNA expression for uncoupling proteins.
AB  - Chronic administration of leptin has been shown to reduce adiposity through
      energy intake and expenditure. The present study aims to examine how acute
      central infusion of leptin regulates peripheral lipid metabolism, as assessed by
      markers indicative of their mobilization and utilization. A bolus infusion of 1
      microg/rat leptin into the third cerebroventricle increased the expression of
      mRNA for hormone-sensitive lipase (HSL), an indicator of lipolysis, in white
      adipose tissue (WAT). This was accompanied by elevation of plasma levels of
      glycerol, but not of free fatty acids, as compared to the saline control (P <
      0.03). The same treatment with leptin decreased plasma insulin levels but did not
      affect the plasma glucose level (P < 0.05 for insulin). Among the major
      regulators of the transportation or utilization of energy substrates, leptin
      treatment increased expression of mRNA for uncoupling protein 1 (UCP1) in brown
      adipose tissue (BAT), UCP2 in WAT, and UCP3 in quadriceps skeletal muscle, but
      not those for fatty acid-binding protein in WAT, carnitine phosphate transferase
      1, a marker for beta oxidation of fatty acids in muscle, nor glucose transporter
      4 in WAT and muscle (P < 0.01 for HSL, P < 0.05 for UCP1, and P < 0.005 for UCP2
      and UCP3). These results indicate that, even in a single bolus, leptin may
      regulate the mobilization and/or utilization of energy substrates such as fatty
      acids by affecting lipolytic activity in WAT and by increasing the expression of
      UCPs in BAT, WAT, and muscle.

PMID- 15734724
TI  - A nonspecific phosphotyrosine phosphatase inhibitor,
      bis(maltolato)oxovanadium(IV), improves glucose tolerance and prevents diabetes
      in Zucker diabetic fatty rats.
AB  - The molecular basis of insulin resistance, a major risk factor for development of
      Type II diabetes, involves defective insulin signaling. Insulin-mediated signal
      transduction is negatively regulated by the phosphotyrosine phosphatase, PTP1B,
      and numerous studies have demonstrated that organo-vanadium compounds, which are
      nonselective phosphotyrosine phosphatase inhibitors, have insulin-mimetic
      properties. However, whether or not vanadium compounds can prevent the transition
      from insulin resistance to overt diabetes is unknown. We compared the ability of
      bis(maltolato)oxovanadium(IV) (BMOV), an orally bioavailable organo-vanadium
      compound, and rosiglitazone maleate (RSG), a known insulin sensitizer, to prevent
      development of diabetes in Zucker diabetic fatty (ZDF) rats. Treatment began at 6
      weeks of age when animals are insulin resistant and hyperinsulinemic, but not yet
      hyperglycemic, and ended at 12 weeks of age, which is 4 weeks after ZDF rats
      typically develop overt diabetes. BMOV-treated ZDF rats did not develop
      hyperglycemia, showed significant improvement in insulin sensitivity, and
      retained normal pancreatic islet morphology and endocrine cell distribution,
      similar to RSG-treated animals. BMOV and RSG treatment also prevented the hyper
      phagia and polydipsia present in untreated ZDF rats; however, BMOV-treated ZDF
      rats gained much less weight than did RSG-treated animals. Circulating levels of
      adiponectin decreased in untreated ZDF rats compared to lean controls, but these
      levels remained normal in BMOV-treated ZDF rats. In contrast, in RSG-treated ZDF
      rats, plasma adiponectin levels were nearly 4-fold higher than in lean control
      rats, primarily as a result of a large increase in the amount of low-molecular
      weight forms of adiponectin in circulation. These data demonstrate that
      phosphatase inhibition offers a new approach to diabetes prevention, one that may
      have advantages over current approaches.

PMID- 15734725
TI  - Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer
      model in vivo.
AB  - Clinical intervention studies and experimental studies with lignan-rich diets
      suggest that lignans may have inhibitory effects on prostate cancer, but no
      clinical or experimental studies with purified lignans have been published. The
      purpose of this study was to investigate the effect of a plant lignan 7
      hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic
      mice. Athymic nude male mice were injected subcutaneously with LNCaP cells.
      Starting 3 days after tumor cell injections, a control diet or a control diet
      supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor
      take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of
      LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take
      rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic
      index compared with controls. Furthermore, the cell proliferation index was
      reduced in mice receiving the 0.30% HMR diet compared with mice receiving the
      control diet. Our results suggest that dietary HMR started at the early phase of
      the tumor development inhibits the growth of the LNCaP human prostate cancer
      xenografts in athymic male mice.

PMID- 15734726
TI  - Pharmacogenetics and human molecular genetics of opiate and cocaine addictions
      and their treatments.
AB  - Opiate and cocaine addictions are major social and medical problems that impose a
      significant burden on society. Despite the size and scope of these problems,
      there are few effective treatments for these addictions. Methadone maintenance is
      an effective and most widely used treatment for opiate addiction, allowing
      normalization of many physiological abnormalities caused by chronic use of short
      acting opiates. There are no pharmacological treatments for cocaine addiction.
      Epidemiological, linkage, and association studies have demonstrated a significant
      contribution of genetic factors to the addictive diseases. This article reviews
      the molecular genetics and pharmacogenetics of opiate and cocaine addictions,
      focusing primarily on genes of the opioid and monoaminergic systems that have
      been associated with or have evidence for linkage to opiate or cocaine addiction.
      This evidence has been marshalled either through identification of variant
      alleles that lead to functional alterations of gene products, altered gene
      expression, or findings of linkage or association studies. Studies of
      polymorphisms in the mu opioid receptor gene, which encodes the receptor target
      of some endogenous opioids, heroin, morphine, and synthetic opioids, have
      contributed substantially to knowledge of genetic influences on opiate and
      cocaine addiction. Other genes of the endogenous opioid and monoaminergic
      systems, particularly genes encoding dopamine beta-hydroxylase, and the dopamine,
      serotonin, and norepinephrine transporters have also been implicated. Variants in
      genes encoding proteins involved in metabolism or biotransformation of drugs of
      abuse and also of treatment agents are reviewed.

PMID- 15734727
TI  - International union of pharmacology. XLV. Classification of the kinin receptor
      family: from molecular mechanisms to pathophysiological consequences.
AB  - Kinins are proinflammatory peptides that mediate numerous vascular and pain
      responses to tissue injury. Two pharmacologically distinct kinin receptor
      subtypes have been identified and characterized for these peptides, which are
      named B1 and B2 and belong to the rhodopsin family of G protein-coupled
      receptors. The B2 receptor mediates the action of bradykinin (BK) and lysyl
      bradykinin (Lys-BK), the first set of bioactive kinins formed in response to
      injury from kininogen precursors through the actions of plasma and tissue
      kallikreins, whereas the B(1) receptor mediates the action of des-Arg9-BK and Lys
      des-Arg9-BK, the second set of bioactive kinins formed through the actions of
      carboxypeptidases on BK and Lys-BK, respectively. The B2 receptor is ubiquitous
      and constitutively expressed, whereas the B1 receptor is expressed at a very low
      level in healthy tissues but induced following injury by various proinflammatory
      cytokines such as interleukin-1beta. Both receptors act through G alpha(q) to
      stimulate phospholipase C beta followed by phosphoinositide hydrolysis and
      intracellular free Ca2+ mobilization and through G alpha(i) to inhibit adenylate
      cyclase and stimulate the mitogen-activated protein kinase pathways. The use of
      mice lacking each receptor gene and various specific peptidic and nonpeptidic
      antagonists have implicated both B1 and B2 receptors as potential therapeutic
      targets in several pathophysiological events related to inflammation such as
      pain, sepsis, allergic asthma, rhinitis, and edema, as well as diabetes and
      cancer. This review is a comprehensive presentation of our current understanding
      of these receptors in terms of molecular and cell biology, physiology,
      pharmacology, and involvement in human disease and drug development.

PMID- 15734728
TI  - Metabolism and disposition kinetics of nicotine.
AB  - Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy
      for smoking cessation, a potential medication for several diseases, and a useful
      probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). We review current
      knowledge about the metabolism and disposition kinetics of nicotine, some other
      naturally occurring tobacco alkaloids, and nicotine analogs that are under
      development as potential therapeutic agents. The focus is on studies in humans,
      but animal data are mentioned when relevant to the interpretation of human data.
      The pathways of nicotine metabolism are described in detail. Absorption,
      distribution, metabolism, and excretion of nicotine and related compounds are
      reviewed. Enzymes involved in nicotine metabolism including cytochrome P450
      enzymes, aldehyde oxidase, flavin-containing monooxygenase 3, amine N
      methyltransferase, and UDP-glucuronosyltransferases are represented, as well as
      factors affecting metabolism, such as genetic variations in metabolic enzymes,
      effects of diet, age, gender, pregnancy, liver and kidney diseases, and racial
      and ethnic differences. Also effects of smoking and various inhibitors and
      inducers, including oral contraceptives, on nicotine metabolism are discussed.
      Due to the significance of the CYP2A6 enzyme in nicotine clearance, special
      emphasis is given to the effects and population distributions of CYP2A6 alleles
      and the regulation of CYP2A6 enzyme.

PMID- 15734729
TI  - Mechanisms of resistance of malaria parasites to antifolates.
AB  - Antifolate antimalarial drugs interfere with folate metabolism, a pathway
      essential to malaria parasite survival. This class of drugs includes effective
      causal prophylactic and therapeutic agents, some of which act synergistically
      when used in combination. Unfortunately, the antifolates have proven susceptible
      to resistance in the malaria parasite. Resistance is caused by point mutations in
      dihydrofolate reductase and dihydropteroate synthase, the two key enzymes in the
      folate biosynthetic pathway that are targeted by the antifolates. Resistance to
      these drugs arises relatively rapidly in response to drug pressure and is now
      common worldwide. Nevertheless, antifolate drugs remain first-line agents in
      several sub-Saharan African countries where chloroquine resistance is widespread,
      at least partially because they remain the only affordable, effective
      alternative. New antifolate combinations that are more effective against
      resistant parasites are being developed and in one case, recently introduced into
      use. Combining these antifolates with drugs that act on different targets in the
      parasite should greatly enhance their effectiveness as well as deter the
      development of resistance. Molecular epidemiological techniques for monitoring
      parasite drug resistance may contribute to development of strategies for
      prolonging the useful therapeutic life of this important class of drugs.

PMID- 15734730
TI  - Disabled-2 (Dab2) is required for transforming growth factor beta-induced
      epithelial to mesenchymal transition (EMT).
AB  - Transforming growth factor beta (TGFbeta) induces an epithelial to mesenchymal
      transition (EMT) during both physiological and pathological processes; however,
      the mechanism underlying this transition is not fully elucidated. Here, we have
      demonstrated that TGFbeta induces the expression of the adaptor molecule disabled
      2 (Dab2) concomitant with the promotion of EMT. We show that TGFbeta induces a
      transient accumulation of Dab2 to the membrane and increases Dab2 binding to
      beta1 integrin. Furthermore, small interfering RNA (siRNA)-mediated silencing of
      Dab2 expression in mouse mammary gland epithelial cells results in inhibition of
      integrin activation, shown by a decrease of both TGFbeta-induced focal adhesion
      kinase phosphorylation and cellular adherence, leading to apoptosis and
      inhibition of EMT. Forced re-expression of human Dab2, not targeted by the mouse
      siRNA sequence, rescues cells from apoptosis and restores TGFbeta-mediated
      integrin activation and EMT. These results are confirmed in the F9
      teratocarcinoma cell line, a model for retinoic acid-induced visceral endoderm
      differentiation in which we demonstrate that ablation of retinoic acid-induced
      Dab2 expression levels, by stable siRNA silencing of Dab2, blocks visceral
      endoderm differentiation. Our findings indicate that Dab2 plays an important
      regulatory role during cellular differentiation and that induction of
      differentiation in the absence of Dab2 expression commits the cell to apoptosis.

PMID- 15734731
TI  - Regulation of BRCA2 gene expression by the SLUG repressor protein in human breast
      cells.
AB  - The expression of the breast cancer susceptibility protein BRCA2 is highly
      regulated in human breast, ovary, and pancreatic cells. BRCA2 is not expressed in
      the non-dividing cells, and expression is cell cycle stage-dependent and is
      elevated in the sporadic cancer cells. Mutational analysis of the upstream
      sequence of the human BRCA2 gene revealed an E2-box-containing silencer at the 
      701 to -921 position. The E2-box is essential for the cell-cycle stage-dependent
      activity of the silencer. We affinity-purified a 29-kDa silencer-binding protein
      (SBP) from the nuclear extracts of human breast cells BT-549 and MDA-MB-231. We
      explored whether the E2-box-binding repressor protein SLUG, which is of similar
      molecular size, is involved in the silencing process. Supershift assay with the
      purified SBP and anti-SLUG antibody revealed the identity of the SBP as SLUG. We
      found that silencer is inactive in the human breast cancer cells such as MDA-MB
      468 and MCF-7 that do not express SLUG, further suggesting the involvement of
      SLUG in the BRCA2 gene silencing. Inducible expression of human SLUG in the
      dividing MDA-MB-468 cells reduced BRCA2 RNA levels with the activation of the
      silencer. Furthermore, small interfering RNA-mediated knockdown of SLUG mRNA in
      the BT-549 cells caused inhibition of the silencer function. Chromatin
      immunoprecipitation assays suggested that SLUG mediates its action by recruiting
      C-terminal-binding protein-1 (CtBP-1) and histone deacetylase-1 (HDAC-1) at the
      silencer E2-box. The general HDAC inhibitor, trichostatin A, inhibited the SLUG
      mediated regulation of the silencer function. It thus appears that SLUG is a
      negative regulator for BRCA2 gene expression.

PMID- 15734732
TI  - Bach1 competes with Nrf2 leading to negative regulation of the antioxidant
      response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression
      and induction in response to antioxidants.
AB  - The antioxidant response element (ARE) and Nrf2 are known to regulate the
      expression and coordinated induction of genes encoding detoxifying enzymes
      including NAD(P)H:quinone oxidoreductase1 (NQO1) in response to antioxidants. In
      this report, we demonstrate that overexpression of the transcription factor Bach1
      in Hep-G2 cells negatively regulated NQO1 gene expression and induction in
      response to antioxidant t-BHQ. Bandshift and supershift assays revealed that
      Bach1 binds to the ARE as a heterodimer with small Maf proteins but not as a
      homodimer or heterodimer with Nrf2. The transfection and ChIP assays revealed
      that Bach1 and Nrf2 competed with each other to regulate ARE-mediated gene
      expression. Heme, a negative regulator of Bach1 relieved the Bach1 repression of
      NQO1 gene expression in transfected cells. The transcription of Bach1 and Nrf2
      did not change in response to t-BHQ. Immunofluorescence assays and Western blot
      analysis revealed that both Bach1 and Nrf2 localized in the cytoplasm and nucleus
      of the untreated cells. The treatment of cells with t-BHQ resulted in the nuclear
      accumulation of both Bach1 and Nrf2. Interestingly, the t-BHQ-induced nuclear
      accumulation of Bach1 was significantly delayed over that of Nrf2. These results
      led to the conclusion that a balance of Nrf2 versus Bach1 inside the nucleus
      influences up- or down-regulation of ARE-mediated gene expression. The results
      further suggest that antioxidant-induced delayed accumulation of Bach1
      contributes to the down-regulation of ARE-regulated genes, presumably to reduce
      the antioxidant enzymes to normal levels.

PMID- 15734733
TI  - Structure of hnRNP D complexed with single-stranded telomere DNA and unfolding of
      the quadruplex by heterogeneous nuclear ribonucleoprotein D.
AB  - Heterogeneous nuclear ribonucleoprotein D, also known as AUF1, has two DNA/RNA
      binding domains, each of which can specifically bind to single-stranded
      d(TTAGGG)n, the human telomeric repeat. Here, the structure of the C-terminal
      binding domain (BD2) complexed with single-stranded d(TTAGGG) determined by NMR
      is presented. The structure has revealed that each residue of the d(TAG) segment
      is recognized by BD2 in a base-specific manner. The interactions deduced from the
      structure have been confirmed by gel retardation experiments with mutant BD2 and
      DNA. It is known that single-stranded DNA with the telomeric repeat tends to form
      a quadruplex and that the quadruplex has an inhibitory effect on telomere
      elongation by telomerase. This time it is revealed that BD2 unfolds the
      quadruplex of such DNA upon binding. Moreover, the effect of BD2 on the
      elongation by telomerase was examined in vitro. These results suggest the
      possible involvement of heterogeneous nuclear ribonucleoprotein D in maintenance
      of the telomere 3'-overhang either through protection of a single-stranded DNA or
      destabilization of the potentially deleterious quadruplex structure for the
      elongation by telomerase.

PMID- 15734734
TI  - Homocysteine down-regulates cellular glutathione peroxidase (GPx1) by decreasing
      translation.
AB  - Hyperhomocysteinemia contributes to vascular dysfunction and an increase in the
      risk of cardiovascular disease. An elevated level of homocysteine in vivo and in
      cell culture systems results in a decrease in the activity of cellular
      glutathione peroxidase (GPx1), an intracellular antioxidant enzyme that reduces
      hydrogen peroxide and lipid peroxides. In this study, we show that homocysteine
      interferes with GPx1 protein expression without affecting transcript levels.
      Expression of the selenocysteine (SEC)-containing GPx1 protein requires special
      translational cofactors to "read-through" a UGA-stop codon that specifies SEC
      incorporation at the active site of the enzyme. These factors include a
      selenocysteine incorporation sequence (SECIS) in the 3'-untranslated region of
      the GPx1 mRNA and cofactors involved in the biosynthesis and translational
      insertion of SEC. To monitor SEC incorporation, we used a reporter gene system
      that has a UGA codon within the protein-coding region of the luciferase mRNA.
      Addition of either the GPx1 or GPx3 SECIS element in the 3'-untranslated region
      of the luciferase gene stimulated read-through by 6-11-fold in selenium-replete
      cells; absence of selenium prevented translation. To alter cellular homocysteine
      production, we used methionine in the presence of aminopterin, a folate
      antagonist, co-administered with hypoxanthine and thymidine (HAT/Met). This
      treatment increased homocysteine levels in the media by 30% (p < 0.01) and
      decreased GPx1 enzyme activity by 45% (p = 0.0028). HAT/Met treatment decreased
      selenium-mediated read-through significantly (p < 0.001) in luciferase constructs
      containing the GPx1 or GPx3 SECIS element; most importantly, the suppression of
      selenium-dependent read-through was similar whether an SV40 promoter or the GPx1
      promoter was used to drive transcription of the SECIS-containing constructs.
      Furthermore, HAT/Met had no effect on steady-state GPx1 mRNA levels but decreased
      GPx1 protein levels, suggesting that this effect is not transcriptionally
      mediated. These data support the conclusion that homocysteine decreases GPx1
      activity by altering the translational mechanism essential for the synthesis of
      this selenocysteine-containing protein.

PMID- 15734735
TI  - Regulation of sphingosine-1-phosphate lyase gene expression by members of the
      GATA family of transcription factors.
AB  - Sphingosine-1-phosphate is a bioactive sphingolipid that regulates proliferation,
      differentiation, migration, and apoptosis. Sphingosine-1-phosphate is
      irreversibly degraded by the highly conserved enzyme sphingosine-1-phosphate
      lyase. Recent studies have suggested that sphingosine-1-phosphate lyase
      expression affects animal development and cell fate decisions. Despite its
      crucial role, mechanisms affecting expression of sphingosine-1-phosphate lyase
      remain poorly understood. In this study, regulation of sphingosine-1-phosphate
      lyase gene expression was investigated in Caenorhabditis elegans, where lyase
      expression is spatially restricted to cells of the developing and adult gut and
      is essential for normal development. Deletion analysis and generation of
      transgenic worms combined with fluorescence microscopy identified a 350
      nucleotide sequence upstream of the ATG start site necessary for maximal lyase
      expression in adult worms. Site-specific mutagenesis of a GATA transcription
      factor-binding motif in the promoter led to loss of reporter expression.
      Knockdown of the gut-specific GATA transcription factor ELT-2 by RNA interference
      similarly led to loss of reporter expression. ELT-2 interacted with the GATA
      factor-binding motif in vitro and was also capable of driving expression of a
      Caenorhabditis elegans lyase promoter-beta-galactosidase reporter in a
      heterologous yeast system. These studies demonstrate that ELT-2 regulates
      sphingosine-1-phosphate lyase expression in vivo. Additionally, we demonstrate
      that the human sphingosine-1-phosphate lyase gene is regulated by a GATA
      transcription factor. Overexpression of GATA-4 led to both an increase in
      activity of a reporter gene as well as an increase in endogenous sphingosine-1
      phosphate lyase protein.

PMID- 15734736
TI  - Vinexin beta interacts with the non-phosphorylated AF-1 domain of retinoid
      receptor gamma (RARgamma) and represses RARgamma-mediated transcription.
AB  - Nuclear retinoic acid receptors (RARs) are ligand-dependent transcription factors
      that regulate the expression of retinoic acid target genes. Although the
      importance of RAR phosphorylation in their N-terminal domain is clearly
      established, the underlying mechanism for the phosphorylation-dependent
      transcriptional activity of the receptors had not been elucidated yet. Here,
      using a yeast two-hybrid system, we report the isolation of vinexin beta as a new
      cofactor that interacts with the N-terminal A/B domain of the RARgamma isotype.
      Vinexin beta is a multiple SH3 motif-containing protein associated with the
      cytoskeleton and also present in the nucleus. We demonstrate that vinexin beta
      colocalizes with RARgamma in the nucleus and interacts with the non
      phosphorylated form of the AF-1 domain of RARgamma. We also show that this
      interaction is prevented upon phosphorylation of the AF-1 domain. Using F9 cells
      stably overexpressing vinexin beta or vinexin knockdown by RNA interference, we
      demonstrate that vinexin beta is an inhibitor of RARgamma-mediated transcription.
      We propose a model in which phosphorylation of the AF-1 domain controls RARgamma
      mediated transcription through triggering the dissociation of vinexin beta.

PMID- 15734737
TI  - Adiponectin inhibits cell proliferation by interacting with several growth
      factors in an oligomerization-dependent manner.
AB  - Adiponectin, an adipocyte-specific secretory protein, is present in serum as
      three oligomeric complexes. Apart from its roles as an anti-diabetic and anti
      atherogenic hormone, adiponectin has been implicated as an important regulator of
      cell growth and tissue remodeling. Here we show that some of these functions
      might be mediated by the specific interactions of adiponectin with several
      important growth factors. Among six different growth factors examined,
      adiponectin was found to bind with platelet-derived growth factor BB (PDGF-BB),
      basic fibroblast growth factor (FGF), and heparin-binding epidermal growth factor
      like growth factor (HB EGF) with distinct affinities. The bindings of adiponectin
      with these growth factors are oligomerization-dependent. PDGF-BB bound to the
      high molecular weight (HMW) and middle molecular weight (MMW) complexes, but not
      to the low molecular weight (LMW) complex of adiponectin. Basic FGF
      preferentially interacted with the HMW form, whereas HB EGF bound to all three
      forms with comparable affinities. These three growth factors did not compete with
      each other for their bindings to adiponectin, suggesting the involvement of
      distinct binding sites. The interactions of adiponectin with PDGF-BB, basic FGF,
      and HB EGF precluded the bindings to their respective membrane receptors and
      attenuated the DNA synthesis and cell proliferation induced by these growth
      factors. Small interfering RNA-mediated down-regulation of adiponectin receptors
      did not affect the suppressive effects of adiponectin on cell proliferation
      stimulated by these growth factors. These data collectively suggest that the
      oligomeric complexes of adiponectin can modulate the biological actions of
      several growth factors by controlling their bioavailability at a pre-receptor
      level and that this effect might partly account for the anti-atherogenic, anti
      angiogenic, and anti-proliferative functions of adiponectin.

PMID- 15734739
TI  - Active site aspartate residues are critical for tryptophan tryptophylquinone
      biogenesis in methylamine dehydrogenase.
AB  - The biosynthesis of methylamine dehydrogenase (MADH) requires formation of six
      intrasubunit disulfide bonds, incorporation of two oxygens into residue betaTrp57
      and covalent cross-linking of betaTrp57 to betaTrp108 to form the protein-derived
      cofactor tryptophan tryptophylquinone (TTQ). Residues betaAsp76 and betaAsp32 are
      located in close proximity to the quinone oxygens of TTQ in the enzyme active
      site. These residues are structurally conserved in quinohemoprotein amine
      dehydrogenase, which possesses a cysteine tryptophylquinone cofactor. Relatively
      conservative betaD76N and betaD32N mutations resulted in very low levels of MADH
      expression. Analysis of the isolated proteins by mass spectrometry revealed that
      each mutation affected TTQ biogenesis. betaD76N MADH possessed the six disulfides
      but had no oxygen incorporated into betaTrp57 and was completely inactive. The
      betaD32N MADH preparation contained a major species with six disulfides but no
      oxygen incorporated into betaTrp57 and a minor species with both oxygens
      incorporated, which was active. The steady-state kinetic parameters for the
      betaD32N mutant were significantly altered by the mutation and exhibited a 1000
      fold increase in the Km value for methylamine. These results have allowed us to
      more clearly define the sequence of events that lead to TTQ biogenesis and to
      define novel roles for aspartate residues in the biogenesis of a protein-derived
      cofactor.

PMID- 15734738
TI  - Distinct conformation-mediated functions of an active site loop in the catalytic
      reactions of NAD-dependent D-lactate dehydrogenase and formate dehydrogenase.
AB  - The three-dimensional structures of NAD-dependent D-lactate dehydrogenase (D-LDH)
      and formate dehydrogenase (FDH), which resemble each other, imply that the two
      enzymes commonly employ certain main chain atoms, which are located on
      corresponding loop structures in the active sites of the two enzymes, for their
      respective catalytic functions. These active site loops adopt different
      conformations in the two enzymes, a difference likely attributable to hydrogen
      bonds with Asn97 and Glu141, which are also located at equivalent positions in D
      LDH and FDH, respectively. X-ray crystallography at 2.4-A resolution revealed
      that replacement of Asn97 with Asp did not markedly change the overall protein
      structure but markedly perturbed the conformation of the active site loop in
      Lactobacillus pentosus D-LDH. The Asn97-->Asp mutant D-LDH exhibited virtually
      the same k(cat), but about 70-fold higher K(M) value for pyruvate than the wild
      type enzyme. For Paracoccus sp. 12-A FDH, in contrast, replacement of Glu141 with
      Gln and Asn induced only 5.5- and 4.3-fold increases in the K(M) value, but 110
      and 590-fold decreases in the k(cat) values for formate, respectively.
      Furthermore, these mutant FDHs, particularly the Glu141-->Asn enzyme, exhibited
      markedly enhanced catalytic activity for glyoxylate reduction, indicating that
      FDH is converted to a 2-hydroxy-acid dehydrogenase on the replacement of Glu141.
      These results indicate that the active site loops play different roles in the
      catalytic reactions of D-LDH and FDH, stabilization of substrate binding and
      promotion of hydrogen transfer, respectively, and that Asn97 and Glu141, which
      stabilize suitable loop conformations, are essential elements for proper loop
      functioning.

PMID- 15734741
TI  - Structural studies of a stabilized phosphoenzyme intermediate of Ca2+-ATPase.
AB  - Ca(2+)-ATPase belongs to the family of P-type ATPases and maintains low
      concentrations of intracellular Ca(2+). Its reaction cycle consists of four main
      intermediates that alternate ion binding in the transmembrane domain with
      phosphorylation of an aspartate residue in a cytoplasmic domain. Previous work
      characterized an ultrastable phosphoenzyme produced first by labeling with
      fluorescein isothiocyanate, then by allowing this labeled enzyme to establish a
      maximal Ca(2+) gradient, and finally by removing Ca(2+) from the solution. This
      phosphoenzyme is characterized by very low fluorescence and has specific
      enzymatic properties suggesting the existence of a high energy phosphoryl bond.
      To study the structural properties of this phosphoenzyme, we used cryoelectron
      microscopy of two-dimensional crystals formed in the presence of decavanadate and
      determined the structure at 8-A resolution. To our surprise we found that at this
      resolution the low fluorescence phosphoenzyme had a structure similar to that of
      the native enzyme crystallized under equivalent conditions. We went on to use
      glutaraldehyde cross-linking and proteolysis for independent structural
      assessment and concluded that, like the unphosphorylated native enzyme, Ca(2+)
      and vanadate exert a strong influence over the global structure of this low
      fluorescence phosphoenzyme. Based on a structural model with fluorescein
      isothiocyanate bound at the ATP site, we suggest that the stability as well as
      the low fluorescence of this phosphoenzyme is due to a fluorescein-mediated cross
      link between two cytoplasmic domains that prevents hydrolysis of the aspartyl
      phosphate. Finally, we consider the alternative possibility that phosphate
      transfer to fluorescein itself could explain the properties of this low
      fluorescence species.

PMID- 15734740
TI  - Relief of p53-mediated telomerase suppression by p73.
AB  - Reactivation of telomerase is a feature in many cancer cells. Telomerase
      activation inhibits telomere shortening, thereby preventing cell cycle arrest and
      apoptosis activated by shortened telomeres or chromosomal rearrangements. The
      tumor-suppressor gene product, p53, was previously shown to transcriptionally
      suppress the activation of the catalytic subunit of telomerase (hTERT). Here we
      have evaluated the role of p73 in hTERT regulation. We found that ectoptic
      expression of p73beta, in contrast to p73alpha or p53, in p53 null H1299 cells
      does not lead to suppression of hTERT transcription. However co-expression of
      p73alpha or p73beta together with p53 abolished p53-mediated hTERT suppression.
      This phenomenon was found to be dependent on the DNA binding ability of p73. We
      also show that p53-mediated suppression of hTERT transcription requires a minimum
      threshold level of p53, and p73 abrogates p53-mediated suppression by reducing
      p53 levels through the activation of HDM2. Moreover, p53-mediated hTERT
      suppression was not relieved by p73beta in cells depleted of HDM2 through small
      interfering RNA-mediated gene silencing. In addition, knockdown of HDM2 in MCF7
      cells, which express moderately high levels of p73 and p53, resulted in the
      reduction of endogenous hTERT levels. Finally, knockdown of p73 in MCF7 cells
      resulted in increased p53 protein levels and a concomitant decrease in hTERT
      levels. Together, our data indicate a plausible way by which p73, through HDM2,
      can oppose p53 tumor suppressor function, thereby possibly contributing to
      tumorigenesis.

PMID- 15734742
TI  - Phospholipid transfer protein deficiency impairs apolipoprotein-B secretion from
      hepatocytes by stimulating a proteolytic pathway through a relative deficiency of
      vitamin E and an increase in intracellular oxidants.
AB  - Genetic deficiency of the plasma phospholipid transfer protein (PLTP) in mice
      unexpectedly causes a substantial impairment in liver secretion of apolipoprotein
      B (apoB), the major protein of atherogenic lipoproteins. To explore the
      mechanism, we examined the three known pathways for hepatic apoB secretory
      control, namely endoplasmic reticulum (ER)/proteasome-associated degradation
      (ERAD), post-ER pre-secretory proteolysis (PERPP), and receptor-mediated
      degradation, also known as re-uptake. First, we found that ERAD and cell surface
      re-uptake were not active in PLTP-null hepatocytes. Moreover, ER-to-Golgi
      blockade by brefeldin A, which enhances ERAD, equalized total apoB recovery from
      PLTP-null and wild-type cells, indicating that the relevant process occurs post
      ER. Second, because PERPP can be stimulated by intracellular reactive oxygen
      species (ROS), we examined hepatic redox status. Although we found previously
      that PLTP-null mice exhibit elevated plasma concentrations of vitamin E, a lipid
      anti-oxidant, we now discovered that their livers contain significantly less
      vitamin E and significantly more lipid peroxides than do livers of wild-type
      mice. Third, to establish a causal connection, the addition of vitamin E or
      treatment with an inhibitor of intracellular iron-dependent peroxidation,
      desferrioxamine, abolished the elevation in cellular ROS as well as the defect in
      apoB secretion from PLTP-null hepatocytes. Overall, we conclude that PLTP
      deficiency decreases liver vitamin E content, increases hepatic oxidant tone, and
      substantially enhances ROS-dependent destruction of newly synthesized apoB via a
      post-ER process. These findings are likely to be broadly relevant to hepatic apoB
      secretory control in vivo.

PMID- 15734744
TI  - Assembly of human immunodeficiency virus precursor gag proteins.
AB  - To investigate the mechanism by which human immunodeficiency virus (HIV)
      precursor Gag (PrGag) proteins assemble to form immature virus particles, we
      examined the in vitro assembly of MACANC proteins, composed of the PrGag matrix,
      capsid, and nucleocapsid domains. In the absence of other components, MACANC
      proteins assembled efficiently at physiological temperature but inefficiently at
      lower temperatures. However, the addition of RNA reduced the temperature
      sensitivity of assembly reactions. Assembly of MACANC proteins also was affected
      by pH because the proteins preferentially formed tubes at pH 6.0, whereas spheres
      were obtained at pH 8.0. Because neither tubes nor spheres were amenable to
      analysis of protein-protein contacts, we also examined the membrane-bound
      assemblies of MACANC proteins. Interestingly, MACANC proteins organized on
      membranes in tightly packed hexameric rings. The observed hexamer spacing of 79.7
      A is consistent with the notion that more PrGag proteins assemble into virions
      than are needed to provide capsid proteins for mature virus cores. Our data are
      also consistent with a model for PrGag contacts in immature virions where capsid
      hexamers are tightly packed, where nucleocapsid domains align beneath capsid C
      terminal domains, and where matrix domains form trimers at the nexus of three
      neighbor hexamers.

PMID- 15734743
TI  - Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break
      repair.
AB  - Mdm2 directly regulates the p53 tumor suppressor. However, Mdm2 also has p53
      independent activities, and the pathways that mediate these functions are
      unresolved. Here we report the identification of a specific association of Mdm2
      with Mre11, Nbs1, and Rad50, a DNA double strand break repair complex. Mdm2 bound
      to the Mre11-Nbs1-Rad50 complex in primary cells and in cells containing
      inactivated p53 or p14/p19ARF, a regulator of Mdm2. Further analysis revealed
      that Mdm2 directly bound to Nbs1 but not to Mre11 or Rad50. Amino acids 198-314
      of Mdm2 were required for Mdm2/Nbs1 association, and neither the N terminus
      forkhead-associated and breast cancer C-terminal domains nor the C terminus Mre11
      binding domain of Nbs1 mediated the interaction of Nbs1 with Mdm2. Mdm2 co
      localized with Nbs1 to sites of DNA damage following gamma-irradiation. Notably,
      Mdm2 overexpression inhibited DNA double strand break repair, and this was
      independent of p53 and ARF, the alternative reading frame of the Ink4alocus. The
      delay in DNA repair imposed by Mdm2 required the Nbs1 binding domain of Mdm2, but
      the ubiquitin ligase domain in Mdm2 was dispensable. Therefore, Nbs1 is a novel
      p53-independent Mdm2 binding protein and links Mdm2 to the Mre11-Nbs1-Rad50
      regulated DNA repair response.

PMID- 15734745
TI  - Identification of the putative staphylococcal AgrB catalytic residues involving
      the proteolytic cleavage of AgrD to generate autoinducing peptide.
AB  - The P2 operon of the staphylococcal accessory gene regulator (agr) encodes four
      genes (agrA, -B, -C, and -D) whose products compose a quorum sensing system: AgrA
      and AgrC resemble a two-component signal transduction system of which AgrC is a
      sensor kinase and AgrA is a response regulator; AgrD, a polypeptide that is
      integrated into the cytoplasmic membrane via an amphipathic alpha-helical motif
      in its N-terminal region, is the propeptide for an autoinducing peptide that is
      the ligand for AgrC; and AgrB is a novel membrane protein that involves in the
      processing of AgrD propeptide and possibly the secretion of the mature
      autoinducing peptide. In this study, we demonstrated that AgrB had endopeptidase
      activity, and identified 2 amino acid residues in AgrB (cysteine 84 and histidine
      77) that might form a putative cysteine endopeptidase catalytic center in the
      proteolytic cleavage of AgrD at its C-terminal processing site. Computer analysis
      revealed that the cysteine and histidine residues were conserved among the
      potential AgrB homologous proteins, suggesting that the Agr quorum sensing system
      homologues might also exist in other Gram-positive bacteria.

PMID- 15734747
TI  - Longitudinal myocardial dysfunction in healthy older subjects as a manifestation
      of cardiac ageing.
AB  - BACKGROUND: Abnormalities of longitudinal left ventricular (LV) contraction and
      relaxation may be early markers of cardiac disease. This study was designed to
      assess the relationship between long-axis LV function and age in healthy
      subjects. METHODS: 118 healthy individuals aged 57 +/-19 years (range 20-90
      years) with no evidence of cardiovascular disease under-went echocardiography
      with Doppler examination of transmitral flow. To assess longitudinal LV function,
      systolic (S(m)), early diastolic (E(m)) and late diastolic (A(m)) mitral annular
      velocities were measured using colour-coded tissue Doppler imaging. RESULTS: The
      left atrium was enlarged (P<0.001) in subjects >/=60 years of age compared to
      those <60 years, but there were no differences in LV volumetric indices and
      ejection fraction. Peak E velocity was lower (P<0.001) and peak A velocity of
      transmitral flow was higher in older subjects (P<0.001) with a higher E/A ratio
      (P<0.001) and longer isovolumic relaxation time (P= 0.001) indicative of impaired
      ventricular relaxation. S m and E m mitral annular velocities decreased (P<0.001)
      and A m velocity increased (P=0.002) in the older group. E m velocity and E m /A
      m ratio showed a strong negative correlation with age (r= -0.80, P<0.001 and r=
      0.78, P<0.001, respectively). CONCLUSIONS: Global LV systolic function is
      preserved but the velocity of long-axis systolic shortening is depressed in older
      individuals, indicating selective impairment of the longitudinal component of
      systolic contraction. The decline in the velocity of early diastolic long-axis LV
      lengthening and the changes in the pattern of transmitral flow suggest impaired
      ventricular relaxation. These measures of cardiac function may be a useful index
      of normal cardiac ageing.

PMID- 15734748
TI  - Operative delivery and postnatal depression: a cohort study.
AB  - OBJECTIVES: To assess the association between elective caesarean section and
      postnatal depression compared with planned vaginal delivery and whether emergency
      caesarean section or assisted vaginal delivery is associated with postnatal
      depression compared with spontaneous vaginal delivery. DESIGN: Prospective
      population based cohort study. SETTING: ALSPAC (the Avon longitudinal study of
      parents and children). PARTICIPANTS: 14,663 women recruited antenatally with a
      due date between 1 April 1991 and 31 December 1992. MAIN OUTCOME MEASURE:
      Edinburgh postnatal depression scale score > or = 13 at eight weeks postnatal on
      self completed questionnaire. RESULTS: Albeit with wide confidence intervals,
      there was no evidence that elective caesarean section altered the odds of
      postnatal depression compared with planned vaginal delivery (adjusted odds ratio
      1.06, 95% confidence interval 0.66 to 1.70, P = 0.80). Among planned vaginal
      deliveries there was similarly little evidence of a difference between women who
      have emergency caesarean section or assisted vaginal delivery and those who have
      spontaneous vaginal delivery (1.17, 0.77 to 1.79, P = 0.46, and 0.89, 0.68 to
      1.18, P = 0.42, respectively). CONCLUSIONS: There is no reason for women at risk
      of postnatal depression to be managed differently with regard to mode of
      delivery. Elective caesarean section does not protect against postnatal
      depression. Women who plan vaginal delivery and require emergency caesarean
      section or assisted vaginal delivery can be reassured that there is no reason to
      believe that they are at increased risk of postnatal depression.

PMID- 15734749
TI  - Antral follicle count and FSH concentration after clomiphene citrate challenge
      test in the prediction of ovarian response during IVF treatment.
AB  - BACKGROUND: We compared: (i) antral follicle count (AFC) in the early follicular
      phase, after the clomiphene citrate challenge test (CCCT) and before ovarian
      stimulation following pituitary down-regulation; and (ii) age of women, body mass
      index, basal and stimulated serum FSH concentrations and AFC in predicting the
      ovarian response of infertile women aged <40 years with basal FSH <10 IU/l on
      recruitment in their first IVF cycle. METHODS: Two months prior to the treatment
      cycle, AFC and basal FSH concentration were determined on day 2-3 of a
      spontaneous period and on day 10 after CCCT. All women received a standard
      stimulation regimen. Ovarian response was represented by the number of oocytes,
      serum estradiol, the duration and dosage of gonadotrophins. RESULTS: There was no
      significant difference between basal, stimulated and down-regulated AFC. AFC
      achieved the best predictive value in relation to the number of oocytes, followed
      by combined FSH concentration (sum of the two FSH concentrations) and age of
      women. Both basal AFC and combined FSH concentration were predictive factors of
      serum estradiol concentration, whereas stimulated FSH concentration was
      predictive of the total dosage of gonadotrophins. CONCLUSION: Combined FSH
      concentration after CCCT provides additional information in predicting ovarian
      response.

PMID- 15734750
TI  - Menstrual-like breakdown and apoptosis in human endometrial explants.
AB  - BACKGROUND: Apoptosis occurs in late secretory and menstrual human endometrium
      and is thought to play an important role in endometrial physiology. Menstrual
      like breakdown has been observed in vitro in endometrial explants. The purpose of
      this study was to assess the role of apoptosis in menstrual-like breakdown in
      human endometrial explants. METHODS: Human endometrial tissue was obtained during
      the mid-secretory phase and cultured with or without estrogen and progesterone.
      The occurrence of breakdown was assessed by histology. Apoptosis was determined
      by gel electrophoresis for the detection of DNA fragmentation and by
      immunohistochemistry using the M30 CytoDEATH and anti-cleaved caspase-3 (CASP3)
      antibodies for the detection of caspase activity. Expression of BCL2 and BAX was
      quantified using real-time PCR analysis. RESULTS: Apoptosis occurred in human
      endometrial explants at all time-points studied. Cleaved CASP3 and M30 antigen
      expression increased in all explants, suggesting the involvement of CASP3 in the
      apoptosis. Low BCL2:BAX ratios were observed in all samples when compared with
      pre-culture controls. Estradiol and progesterone supplementation of the culture
      media reduced or eliminated menstrual-like breakdown but did not affect the
      degree of apoptosis observed. CONCLUSIONS: The apoptosis observed in endometrium
      during the late secretory phase and menstrual phase does not appear to be
      mechanistically related to the tissue breakdown but rather may be involved in the
      impending remodelling that occurs in the endometrium in the transition from
      secretory to proliferative phase following the menses.

PMID- 15734751
TI  - Solo mothers and their donor insemination infants: follow-up at age 2 years.
AB  - BACKGROUND: Findings are presented of the second phase of a longitudinal study of
      solo-mother families created through donor insemination (DI). METHODS: At the
      time of the child's second birthday, 21 solo DI mother families were compared
      with 46 married DI families on standardized interview and questionnaire measures
      of the psychological well being of the mothers, mother-child relationships and
      the psychological development of the child. RESULTS: The solo DI mothers showed
      greater pleasure in their child and lower levels of anger accompanied by a
      perception of their child as less 'clingy'. Fewer emotional and behavioural
      difficulties were shown by children of solo than married DI mothers. CONCLUSIONS:
      The findings from this first cohort of solo DI families to be studied lend
      further weight to the view that these women represent a distinct subgroup of
      single parents, who, out of a strong desire for a child, have made the active
      choice to go it alone. Moreover, this route to parenthood does not necessarily
      seem to have an adverse effect on mothers' parenting ability or the psychological
      adjustment of the child.

PMID- 15734752
TI  - Anti-Mullerian hormone concentrations in maternal serum during pregnancy.
AB  - BACKGROUND: In females, anti-Mullerian hormone (AMH) is expressed only by the
      ovary. AMH is secreted by the granulosa cells of ovarian follicles and appears to
      regulate early follicle development. AMH is detected in serum from women of
      reproductive age and its levels vary slightly with the menstrual cycle, reaching
      the peak value in the late follicular phase. This study investigated serum AMH
      levels throughout gestation and after delivery in healthy pregnant women.
      METHODS: This cross-sectional study recruited pregnant women and healthy non
      pregnant women, 84 in total. AMH, FSH and E2 were measured in the follicular
      phase, in the three trimesters of pregnancy and in early puerperium. RESULTS:
      Estradiol and FSH levels followed the expected patterns during gestation. During
      the follicular phase of the menstrual cycle AMH levels were 1.9 +/- 0.5 ng/ml. In
      the three trimesters of pregnancy and in early puerperium AMH levels were: 2.1 +/
      0.56, 2.4 +/- 0.64, 1.95 +/- 0.6 and 2.05 +/- 0.55 ng/ml respectively. No
      significant modifications were found in AMH levels during pregnancy and in the
      early puerperium. CONCLUSIONS: This study has obtained information on AMH and on
      the possible relationship with FSH. We hypothesize that the profile of the new
      marker of ovarian activity AMH may indicate that initial non-cyclic ovarian
      follicular activity during pregnancy is not abolished. Moreover FSH, does not
      seem to play a direct role on AMH synthesis and secretion.

PMID- 15734753
TI  - The high incidence of meiotic errors increases with decreased sperm count in
      severe male factor infertilities.
AB  - BACKGROUND: The high frequency of aneuploidy sperm raises concerns that there may
      be an increased incidence of aneuploid offspring in ICSI programmes. In order to
      assess the role that chromosome complement plays in normal and abnormal
      fertility, detailed molecular cytogenetic studies must be done on sperm samples
      from men with normal and abnormal fertility. METHODS: To understand more clearly
      the cytogenetic make-up of sperm from oligoasthenoteratozoospermic (OAT)
      patients, multi-colour fluorescence in situ hybridization was used to determine
      numerical chromosome abnormalities. RESULTS: Increased aneuploidy frequencies for
      chromosomes 13, 18, 21, X and Y were detected in sperm from OAT patients. The
      frequencies of diploidy also increased. There were no differences in non
      disjunction at meiosis I compared to meiosis II. Sperm count inversely correlated
      with the frequencies of diploidy, aneuploidies for chromosomes 13 and 21 in OAT
      patients. Twenty-two cycles of ICSI and 18 embryo transfers were performed in 20
      couples. Only three cases achieved successful pregnancies. CONCLUSIONS: A higher
      incidence of meiotic errors and lower sperm counts was found in sperm from OAT
      patients.

PMID- 15734754
TI  - High magnitude of light retardation by the zona pellucida is associated with
      conception cycles.
AB  - BACKGROUND: Failures in expression of zona proteins correlate to subfertility in
      animals. Low expression of the zona proteins by the growing human oocyte may
      indicate reduced developmental potential. Therefore, we non-invasively analysed
      the thickness and the structure of the zona pellucida (ZP) of human oocytes with
      respect to embryo fate after ICSI. METHODS: Retardance magnitude and thickness of
      the inner, middle and outer layers of the ZP were quantitatively analysed by a
      Polscope in 166 oocytes selected for transfer after ICSI (63 patients; 32.8 +/-
      4.4 years) on the basis of pronuclear score at day 1. Blastomere number was
      determined at day 2. Data were compared between conception cycles (CC; 65
      oocytes/23 patients) and non-conception cycles (NCC; 101 oocytes/40 patients) and
      with respect to maternal age. RESULTS: The thickness was slightly elevated (P <
      0.001), and the mean magnitude of light retardance was nearly 30% higher (P <
      0.001) in the inner layer of the zona pellucida of oocytes contributing to CC
      compared to NCC. Embryos in the CC group tended to develop faster. CONCLUSIONS:
      The magnitude of light retardance by the zona pellucida inner layer appears to
      present a unique non-invasive marker for oocyte developmental potential.

PMID- 15734755
TI  - Secretion of cytokines and chemokines by polarized human epithelial cells from
      the female reproductive tract.
AB  - BACKGROUND: Pro-inflammatory chemokines that attract and cytokines that activate
      immune cells contribute to normal physiological homeostasis in the female
      reproductive tract, and are needed to deal effectively with potential pathogenic
      microbes. Mucosal epithelial cells are capable of producing these factors that
      communicate with cells of the innate and adaptive immune systems. METHODS:
      Epithelial cells from Fallopian tube, endometrium and endocervix were isolated
      and grown to high transepithelial resistance in cell inserts from seven patients
      who had hysterectomies. Interleukin (IL)-8, IL-6, granulocyte colony-stimulating
      factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), granulocyte
      macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF
      alpha) and macrophage inflammatory peptide-1beta (MIP-1beta) were assessed by
      Luminex bead analysis or enzyme-linked immunosorbent assay (ELISA) in epithelial
      cell conditioned media from the apical and basolateral compartments. RESULTS:
      With the exception of MCP-1, the seven chemokines/cytokines constitutively
      produced by the polarized epithelial cells were preferentially secreted apically.
      A concentration pattern was found in all cases, with IL-8 and IL-6 produced in
      the greatest quantity. CONCLUSIONS: The concentrations of IL-8, IL-6, G-CSF and
      MCP-1 are similar to the levels found in reproductive tract fluids of patients
      with infection. The constitutive secretion and compartmentalization of large
      quantities of bioactive chemokines and cytokines provide additional evidence for
      the role of epithelial cells as gatekeepers of innate immune protection in the
      female reproductive tract.

PMID- 15734756
TI  - Progestogens stimulate prostacyclin production by human endothelial cells.
AB  - BACKGROUND: The effects of progestogens on endothelial physiology are poorly
      studied. Prostacyclin is a potent vasodilator synthesized by two isoforms of
      cyclooxygenase (COX) in endothelium. We examined the effects of two clinically
      used progestogens, progesterone and medroxyprogesterone acetate (MPA), on
      prostacyclin production by cultured human umbilical vein endothelial cells
      (HUVEC) and the possible role of progesterone receptors and both COX enzymes.
      METHODS: Cells were exposed to 1-100 nmol/l of either progesterone or MPA and
      prostacyclin production was measured in culture medium. RESULTS: Both
      progestogens significantly increased prostacyclin release in a time- and dose
      dependent manner, being higher than control after 24 h. Progesterone and MPA,
      both at 10 nmol/l, increased mRNA expression and protein content of both COX. All
      these effects were mediated through progesterone receptor activation, since they
      were abolished by treatment of cells with the progesterone receptor antagonist RU
      486. Selective inhibitors of COX-1 and -2 (SC-560 and NS-398 respectively)
      reduced basal prostacyclin release, and eliminated increased production in
      response to progestogens. In combination with estradiol, progestogens had an
      additive effect without eliminating estradiol-induced prostacyclin production.
      CONCLUSIONS: Our results support the hypothesis that progesterone and MPA
      increased HUVEC prostacyclin production in a progesterone receptor-dependent
      manner, by enhancing COX-1 and COX-2 expression and activities.

PMID- 15734757
TI  - Differentiation and development of human female germ cells during prenatal
      gonadogenesis: an immunohistochemical study.
AB  - BACKGROUND: In the development of the human ovary, the second trimester includes
      the transition from oogonial replication to primordial follicle formation. The
      present study was carried out to assess differentiation and proliferation of germ
      cells in a series of female gonads from 19 fetuses from the second and third
      trimester, and two neonates. METHODS: Using immunohistochemistry, the following
      markers were studied: placental/germ-like cell alkaline phosphatases (PLAP), the
      marker of pluripotency OCT3/4, the proliferation marker Ki-67, beta-catenin and E
      cadherin, the stem cell factor receptor c-KIT, and VASA, a protein specific for
      the germ cell lineage. RESULTS: PLAP and OCT3/4 were seen during oogenesis, but
      not in germ cells engaged in folliculogenesis. A similar pattern was observed for
      Ki-67. Loss of pluripotency occurs once oocytes engage in follicle formation,
      suggesting a role of cell-cell interactions in the process of germ cell
      maturation. VASA, c-KIT, beta-catenin and E-cadherin were found in germ cells at
      all developmental stages of oogenesis and folliculogenesis. CONCLUSIONS:
      Immunohistochemically, two groups of germ cells can be distinguished. Germ cells
      that are predominantly found in the cortical region of the ovary before weeks 22
      24 of gestation, showing an immature phenotype, are mitotically active, and
      express OCT3/4, a marker of pluripotency. On the other hand, germ cells
      undergoing folliculogenesis have lost their pluripotent potential and no longer
      proliferate.

PMID- 15734758
TI  - Prolonged HCG action affects angiogenic substances and improves follicular
      maturation, oocyte quality and fertilization competence in patients with
      polycystic ovarian syndrome.
AB  - BACKGROUND: The aim of this study was to determine whether, in polycystic ovarian
      syndrome (PCOS) patients, HCG action prolonged for 4 h improves the action of
      angiogenic substances [ovarian renin angiotensin system and vascular endothelial
      growth factor (VEGF)], and consequently follicular maturation, oocyte quality and
      oocyte fertilization competence. METHODS: In this prospective study 20 patients
      with PCOS undergoing IVF were included. Oocyte retrieval was carried out either
      34 or 38 h after HCG administration. Each follicle was analysed for prorenin,
      active renin, VEGF and estradiol. Oocytes were evaluated for quality (mature,
      immature, degenerated oocytes), as were the embryos (low or high). RESULTS: In
      the HCG +38 h group there were 245 follicles, and in the HCG +34 h group 240
      follicles. In the HCG +38 h group, log active renin was lower (2.78 +/- 0.20
      versus 2.91 +/- 0.25; P < 0.001) and VEGF higher (2276.0 +/- 790.1 versus 1946.6
      +/- 954.5 pg/ml; P < 0.001). The odds ratio for obtaining oocytes from follicles
      was 1.6 [95% confidence interval (CI) 1.1-2.6; P = 0.02], and for developing high
      quality embryos 7.6 (95% CI 2.8-20.9; P < 0.001) in favour of the HCG +38 h
      group. CONCLUSIONS: Follicular maturation and oocyte quality are related to the
      intrafollicular influences of active renin and VEGF in a time-dependent manner
      after HCG administration, whereas fertilization competence is related to VEGF
      only.

PMID- 15734759
TI  - The couple's decision-making in IVF: one or two embryos at transfer?
AB  - BACKGROUND: The aim of this study was to evaluate the decision-making process and
      factors that contribute to the decision of IVF participants to choose one or two
      embryos at transfer. METHODS: Two hundred and seventy-four IVF patients equally
      distributed in males and females were personally interviewed using a semi
      structured questionnaire which included 82 items. RESULTS: In the whole study
      population, previous childbirth [odds ratio (OR) 2.1; 95% confidence interval
      (CI) 1.9-3.6], and spare embryos to freeze (OR 23.6; 95% CI 11.2-54.5) emerged as
      the most important variables in patients who had one embryo transferred, while
      previous IVF treatments (OR 0.3; 95% CI 0.1-0.6) and the assumed increased
      pregnancy chance (OR 0.1; 95% CI 0.05-0.3) were the most important decision
      making factors among those who had two embryos. The women were more satisfied
      with the information (83 versus 71%; P = 0.02), and more aware of the risks with
      twin pregnancies (77 versus 66%; P = 0.03) than the males. The women were also
      more concerned about their age. Knowledge about risks of multiple pregnancies was
      higher in females (77%) than in males (66%, P = 0.03). CONCLUSION: The results of
      this study indicate that despite good information about the risks for
      complications with multiple pregnancies, many patients wish to have two embryos
      transferred. Spare embryos to freeze, improvement of pregnancy rate in single
      embryo transfer and young age of the woman are predictive of choosing single
      embryo transfer. However, the final decision must always be made in agreement
      with the physician.

PMID- 15734760
TI  - Reproduction of menstrual changes in transplanted human endometrial tissue in
      immunodeficient mice.
AB  - BACKGROUND: Cultures of human endometrial tissue are useful for analysing the
      mechanisms underlying the menstrual cycle. However, long-term culture of
      endometrial tissue is difficult in vitro. Xenotransplantation of normal human
      endometrial tissue into immunodeficient mice could allow prolonged survival of
      the transplanted tissues. METHODS: Proliferative-phase endometrial tissue samples
      from three women were transplanted into the subcutaneous space of ovariectomized,
      immunodeficient, non-obese diabetic (NOD)/severe combined immunodeficiency
      (SCID)/gammaC(null) (NOG) mice. The mice were treated with 17beta-estradiol (E2)
      for the first 14 days after transplantation, followed by E2 plus progesterone for
      the next 14 days. The transplants were investigated morphologically and
      immunohistochemically at various times after implantation. RESULTS: The
      transplanted tissues contained large numbers of small glands,
      pseudostratification of the nuclei and dense stroma after treatment with E2
      alone. After treatment with E2 plus progesterone, subnuclear vacuolation, luminal
      secretion and decidualization of the stroma were observed. When the hormone
      treatment ceased, tissue destruction occurred and the transplants returned to the
      proliferative phase. Lymphocytes were identified immunohistochemically: the
      numbers of CD56-positive and CD16-negative cells increased significantly in the
      stroma during the late secretory phase (day 28). CONCLUSIONS: Human endometrial
      tissue transplanted into NOG mice showed similar histological changes to eutopic
      endometrial tissue during treatment with sex steroid hormones for 1 month.
      Moreover, lymphocytes were produced in the transplanted human endometrial tissue.
      This system represents a new experimental model of the human endometrium in vivo.

PMID- 15734761
TI  - The use of enzyme-linked immunosorbent assay for detection of Mycoplasma hominis
      antibodies in infertile women serum samples.
AB  - BACKGROUND: Besides Chlamydiae trachomatis and Mycoplasma genitalium, Mycoplasma
      hominis may also cause infertility due to damage of the Fallopian tubes.
      Therefore serum samples from infertile women were analyzed for antibodies to M.
      hominis. METHODS: Sera from 304 infertile women were investigated for
      seropositivity to M. hominis by immunoblotting and a developed ELISA. Women were
      classified into groups based on the type of infertility: infertile due to lack of
      passage in Fallopian tubes (TFI, tubal factor infertility), an infertile male
      partner (MFI, male factor infertility) and unexplained infertility (UFI,
      unexplained factor infertility). Three M. hominis isolates were used in the
      immunoblotting analysis and clear differences in patient immunoprofiles were
      observed between two isolates. For the ELISA we used a mixture of Triton X-114
      extracted membrane proteins from those two M. hominis isolates as antigen.
      RESULTS: Ninety-seven sera (32%) were seropositive to M. hominis when tested by
      the ELISA. There was a significant correlation between TFI and seropositivity to
      M. hominis (P = 0.0015, OR = 2.21, CI = 1.35-3.61). We compared the
      seropositivity of 304 patients to M. hominis with the presence of antibodies
      against two other bacteria Chlamydiae trachomatis and Mycoplasma genitalium and
      there was no statistical correlation between those bacteria and M. hominis.
      CONCLUSION: Our results indicate that M. hominis may be an independent predictor
      of TFI.

PMID- 15734762
TI  - Endometrial micropolyps at fluid hysteroscopy suggest the existence of chronic
      endometritis.
AB  - BACKGROUND: At fluid hysteroscopy the presence of endometrial micropolyps (less
      than 1 mm of size) is a frequent finding. Although their origin is still unknown,
      in our experience they are associated with stromal edema, endometrial thickening
      and periglandular hyperhaemia that suggest the existence of chronic endometritis.
      This study will aim to describe these lesions and evaluate their inflammatory
      significance by comparing hysteroscopic and histological findings. METHODS: 820
      women underwent hysteroscopy and endometrial biopsy. Sensitivity, specificity,
      positive and negative predictive values and accuracy of the micropolyps presence
      for the diagnosis of chronic endometritis were calculated. RESULTS: Micropolyps
      were found in 96 cases (11.7% of all hysteroscopies); in 90 (93.7%) of these
      cases histology confirmed the presence of chronic endometritis. In women without
      micropolyps, chronic endometritis was significantly less frequent (78 cases,
      10.8%) (P < 0.000001). The likelihood of chronic endometritis for women with
      micropolyps was very high (odds ratio 124.2, confidence interval 50.3-205.4). The
      sensitivity, specificity, positive and negative predictive values were 54%, 99%,
      94% and 89%, respectively; the diagnostic accuracy was 90%. CONCLUSIONS: The
      presence of endometrial micropolyps at fluid hysteroscopy is significantly
      associated with endometrial inflammation and can be considered a reliable
      diagnostic sign for this pathology.

PMID- 15734763
TI  - Sex ratios in California following the terrorist attacks of September 11, 2001.
AB  - BACKGROUND: Natural and man-made disasters as well as declining economies appear
      to coincide with reduced odds of male live births among humans (i.e. lower
      secondary sex ratio). This association has been attributed to excess death of
      males in gestation and to reduced conception of males. We attempt to empirically
      discriminate between these two attributions by testing the hypotheses that the
      attacks of September 11, 2001 were followed in California first by higher fetal
      death sex ratios and later by lower sex ratios among very low weight births and
      total live births. METHODS: We apply interrupted time-series methods to the fetal
      death, very low birth weight, and secondary sex ratios. The methods control for
      trends, seasonal cycles, and other forms of autocorrelation that could induce
      spurious associations. RESULTS: Findings support the excess death explanation in
      that the fetal death sex ratio reached its highest level in the 6 year test
      period in October and November of 2001, while the very low weight birth sex ratio
      dropped to its lowest level in 14 years in December of 2001. The secondary sex
      ratio exhibited its second lowest value in 14 years in December of 2001. No
      support was found for the reduced conception explanation in that the sex ratio
      did not differ from expected values 9, 10 or 11 months after the attacks.
      CONCLUSIONS: We infer support for the excess death explanation at the expense of
      the reduced conception explanation. We also describe the implications of our
      findings for public health planning.

PMID- 15734764
TI  - Possible implication of midkine in the development of endometriosis.
AB  - BACKGROUND: The present study was conducted to assess whether midkine (MK), a
      multifunctional molecule known to stimulate tumor growth, may be involved in the
      development of endometriosis. METHODS: The mitogenic activity of MK on cultured
      endometriotic stromal cells was examined by measuring 5-bromo-2'-deoxyuridine
      (BrdU) incorporation. Concentrations of MK in the peritoneal fluid (PF) of women
      without or with endometriosis and those under GnRH agonist treatment were
      measured using a specific enzyme immunoassay. The expression of MK mRNA in
      peritoneal bone marrow-derived cells, peritoneum and endometriotic tissues was
      evaluated by RT-PCR. RESULTS: MK significantly increased BrdU incorporation into
      the DNA of cultured endometriotic stromal cells. The MK concentrations in the PF
      of the women with advanced endometriosis (stages II, III and IV) Median: 1.21
      ng/ml; interquartile range 0.80-2.27 were significantly higher than those of the
      women without endometriosis and with stage I endometriosis (0.06 ng/ml, 0.67
      1.26, P < 0.05). As for the menstrual phase, the MK concentration in PF in the
      inteal phase (1.32 ng/ml. 0.72-2.21) were significantly higher than those in the
      follicular phase (0.95 ng/ml, 0.68-1.24, P < 0.05). In addition, women with
      adnexal adhesions had higher concentrations of MK in PF than those without
      adhesions (P < 0.05). The MK concentrations of the women under GnRH agonist
      treatment were significantly lower than those of the other groups (P < 0.001).
      The expression of MK mRNA was detected in peritoneal bone marrow-derived cells,
      peritoneum and endometriotic tissues. CONCLUSIONS: The present findings suggest
      that MK may play roles, such as stimulation of endometriotic cell proliferation,
      in the development of endometriosis.

PMID- 15734765
TI  - Diuretic usage in heart failure: a continuing conundrum in 2005.
AB  - Several large well-designed clinical trials have shown that the use of diuretics
      is beneficial in patients with hypertension. However, similarly robust data
      regarding their role in chronic heart failure are lacking. Historically,
      diuretics were developed for treatment of sodium and water retention in
      oedematous disorders and clinically, they remain the most potent drugs available
      to relieve symptoms and eliminate oedema in the congested patient with heart
      failure. In the non-congested patient, however, diuretics continue to be used on
      a purely clinical basis without sufficient characterization of benefits, adverse
      effects, and potential influence on mortality. There are also concerns that
      chronic diuretic usage can cause adverse vascular effects, unfavourable
      neuroendocrine activation, electrolyte imbalances, and life-threatening
      arrhythmias. In this article, we review the limited evidence available regarding
      the benefits and perils of using diuretics in heart failure.

PMID- 15734766
TI  - Atherosclerosis regression and TP receptor inhibition: effect of S18886 on plaque
      size and composition--a magnetic resonance imaging study.
AB  - AIMS: Endothelial dysfunction, platelet hyperactivity, and inflammation play a
      crucial role in atherogenesis. A growing body of evidence suggests that
      inhibition of the thromboxane A2 (TxA2 or TP) receptor may improve endothelial
      function and reduce the inflammatory component of atherosclerosis in addition to
      its demonstrated antiplatelet activity. Consequently, we sought to assess the
      effect of a novel TP receptor antagonist S18886, on atherosclerotic lesion
      progression and composition by serial non-invasive magnetic resonance imaging
      (MRI). METHODS AND RESULTS: S18886 was compared with control in an experimental
      model of established aortic atherosclerosis in New Zealand White rabbits (n=10).
      The animals underwent MRI of the abdominal aorta at the time of randomization and
      at the end of treatment. Subsequently, animals were euthanized and specimens were
      stained for histopathology and immunohistochemistry with anti-alpha-actin
      antibodies for vascular smooth muscle cells (VSMC), anti-RAM-11 for macrophages,
      anti-caspase-3 for apoptotic cells, anti-MMP-1 for metalloproteinases, and anti
      endothelin-1 (ET-1) as a marker of endothelial dysfunction. MRI analysis revealed
      a significant reduction in total vessel area (TVA) and vessel wall area (VWA) in
      the S18886 group (P<0.05). Immunostaining analysis showed a significant decrease
      in RAM-11, caspase-3, MMP-1, ET-1 and an increase in alpha-actin in the treated
      group (P<0.05 vs. control). CONCLUSION: Inhibition of the TP receptor by S18886
      causes a regression of advanced atherosclerotic plaques. In addition, the
      reduction in the markers for macrophages, apoptotic cells, metalloproteinases,
      and endothelin-1 and the increase in VSMC, suggests that S18886 may not only halt
      the progression of atherosclerosis, but also transform lesions towards a more
      stable phenotype. The possibility of combining antithrombotic and
      antiatherosclerotic activity by means of the administration of TP inhibitors
      deserves further investigation in a clinical setting.

PMID- 15734767
TI  - One year outcomes with abciximab vs. placebo during percutaneous coronary
      intervention after pre-treatment with clopidogrel.
AB  - AIMS: In the Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action
      for Coronary Treatment Trial, the use of abciximab in patients undergoing
      percutaneous coronary intervention (PCI) after pretreatment with 600 mg
      clopidogrel for >2 h was associated with no clinically measurable benefit at 30
      days. We assessed whether there was any clinical benefit from abciximab at 1 year
      follow-up. METHODS AND RESULTS: After pre-treatment with 600 mg clopidogrel, a
      total of 2159 patients undergoing PCI for stable or unstable angina without
      marked ST-segment shifts or positive biomarkers were randomly assigned to receive
      abciximab or placebo. The occurrence of the composite endpoint of death,
      myocardial infarction, or target vessel revascularization was assessed at 1 year
      after randomization. At 1 year, the composite endpoint occurred in 23.8% of the
      patients in each group [relative risk (RR), 1.01; 95% confidence interval (CI),
      0.85-1.20; P=0.92]. The combined incidence of death and myocardial infarction was
      6.0% in the abciximab group and 6.4% in the placebo group (RR, 0.94; 95% CI, 0.67
      1.32; P=0.73). The mortality rate was 2.1% in the abciximab group and 2.4% in the
      placebo group (RR, 0.88; 95% CI, 0.50-1.54; P=0.66). No trend towards clinical
      benefit was observed with abciximab at 1 year in any subgroup analysed.
      CONCLUSION: In patients with a low-to-intermediate risk profile undergoing PCI
      after pre-treatment with a 600 mg clopidogrel for at least 2 h, the use of
      abciximab offers no additional clinical benefit at 1 year.

PMID- 15734768
TI  - Combined prognostic utility of ST-segment recovery and myocardial blush after
      primary percutaneous coronary intervention in acute myocardial infarction.
AB  - AIMS: ST-segment recovery (SigmaSTR) and myocardial blush (MB) evaluate different
      elements of microcirculatory integrity after reperfusion therapy in acute
      myocardial infarction (AMI). We sought to determine whether the combination of
      SigmaSTR and MB after primary percutaneous coronary intervention (PCI) in AMI has
      greater prognostic utility than either measure alone. METHODS AND RESULTS: The 30
      days and 1 year clinical outcomes of 456 patients were assessed as a function of
      SigmaSTR and MB after primary PCI from the CADILLAC trial. SigmaSTR and MB were
      concordant (> or =70% SigmaSTR and MB grade 2/3 or <70% SigmaSTR and MB grade
      0/1) in 60.1% of patients and discordant in 39.9% of patients. The greatest
      survival was observed among patients with complete SigmaSTR (> or =70%) and MB
      grade 2/3 in whom the cumulative rates of death at 30 days and 1 year were 0.6
      and 1.2%, respectively. Poorest survival was observed among patients with
      incomplete SigmaSTR (<70%) and reduced MB (grade 0/1), in whom 30 days and 1 year
      rates of death were 8.3 and 10.1%, respectively. Intermediate outcomes were
      present in patients with discordant MB and SigmaSTR. By multivariable analysis,
      however, SigmaSTR was an independent correlate of survival at 30 days and 1 year
      (P=0.05 and 0.01, respectively), whereas MB was no longer predictive (P=0.38 and
      0.72, respectively). CONCLUSION: SigmaSTR and MB are not infrequently discordant
      after primary PCI. By univariate analysis, both measures of reperfusion success
      strongly correlate with survival and assessment of both yields incremental
      prognostic information beyond either measure alone. By multivariable analysis,
      however, SigmaSTR is the stronger prognostic variable.

PMID- 15734769
TI  - Comparison of synchrotron radiation angiography with conventional angiography for
      the diagnosis of in-stent restenosis after percutaneous transluminal coronary
      angioplasty.
AB  - AIMS: Synchrotron radiation angiography (SRA) is a novel tool for minimally
      invasive coronary artery imaging. The method uses subtraction of two images
      produced at energies bracketing the iodine K-edge after intravenous infusion of
      iodinated contrast agent. We investigated the accuracy of SRA for detecting in
      stent restenosis (ISR). METHODS AND RESULTS: We recruited 57 men, 4-6 months
      after successful PTCA. We visualized the right coronary artery (RCA) in 27
      patients with 36 stented segments [12 segments with ISR>50% by quantitative
      coronary angiography (QCA)], and the left anterior descending artery (LAD) in 30
      patients with 37 stented segments (10 ISR). SRA and QCA were performed within 2
      days of each other. Two experienced observers unaware of QCA data evaluated the
      SRA results. Image quality was good or excellent in most patients. Global
      sensitivity was 64%, specificity was 95%, and positive and negative predictive
      values were approximately 85%. Inter-observer kappa concordance coefficient was
      0.86. False negatives involved short eccentric lesions and superimposed segments,
      most frequently of the LAD. False positives occurred in intermediate stenoses
      slightly overestimated by SRA. CONCLUSION: In men, this minimally invasive
      approach, using small radiation doses, detects significant ISR in the RCA, but
      the LAD poses difficulties because of superimposition with others structures.

PMID- 15734770
TI  - Mobilization of bone marrow-derived stem cells after myocardial infarction and
      left ventricular function.
AB  - AIMS: Recent data suggest that the administration of bone marrow-derived stem
      cells (BMSC) might improve myocardial perfusion and left ventricular (LV)
      function after acute myocardial infarction (AMI). The aim of this study was to
      assess spontaneous mobilization of BMSC expressing the haematopoietic and
      endothelial progenitor cell-associated antigen CD34+ after AMI and its relation
      to post-infarction remodelling. METHODS AND RESULTS: Peripheral blood
      concentration of CD34+ BMSC was measured by flow cytometry in 54 patients with
      AMI, 26 patients with chronic stable angina (CSA), and 43 normal healthy
      subjects. In patients with AMI, LV function was measured by 2D-echocardiography.
      Eighteen AMI patients were reassessed at 1 year. BMSC concentration was higher in
      patients with AMI (mean peak value: 7.04+/-6.27 cells/microL), than in patients
      with CSA (3.80+/-2.12 cells/microL, P=0.036) and in healthy controls (1.87+/-1.52
      cells/microL, P<0.001). At multivariable analysis statin use (P<0.001), primary
      percutaneous intervention (P=0.048) and anterior AMI (P=0.05) were the only
      independent predictors of increased BMSC mobilization after AMI. In the 28
      patients without subsequent acute coronary events reassessed at 1 year follow-up,
      CD34+ cell concentration was an independent predictor of global and regional
      improvement of LV function (r=0.52, P=0.004 and r=-0.41, P=0.03, respectively).
      CONCLUSION: AMI is followed by enhanced spontaneous mobilization of BMSC, in
      particular, in patients on statin therapy and following a primary percutaneous
      intervention. More importantly persistent spontaneous mobilization of BMSC might
      contribute to determine a more favourable post-AMI remodelling.

PMID- 15734771
TI  - Randomized comparison of intra-aortic balloon support with a percutaneous left
      ventricular assist device in patients with revascularized acute myocardial
      infarction complicated by cardiogenic shock.
AB  - AIMS: Mortality in cardiogenic shock (CS) following acute myocardial infarction
      (AMI) remains unacceptably high despite percutaneous coronary intervention (PCI)
      of the infarcted artery and use of intra-aortic balloon pump (IABP)
      counterpulsation. A newly developed percutaneous left ventricular assist device
      (VAD) (Tandem Heart, Cardiac Assist, Pittsburgh, PA, USA) with active circulatory
      support might have positive haemodynamic effects and decrease mortality. METHODS
      AND RESULTS: Patients in CS after AMI, with intended PCI of the infarcted artery,
      were randomized to either IABP (n=20) or percutaneous VAD support (n=21). The
      primary outcome measure cardiac power index, as well as other haemodynamic and
      metabolic variables, could be improved more effectively by VAD support from 0.22
      [interquartile range (IQR) 0.19-0.30] to 0.37 W/m2 (IQR 0.30-0.47, P<0.001) when
      compared with IABP from 0.22 (IQR 0.18-0.30) to 0.28 W/m2 (IQR 0.24-0.36, P=0.02;
      P=0.004 for intergroup comparison). However, complications like severe bleeding
      (n=19 vs. n=8, P=0.002) or limb ischaemia (n=7 vs. n=0, P=0.009) were encountered
      more frequently after VAD support, whereas 30 day mortality was similar (IABP 45%
      vs. VAD 43%, log-rank, P=0.86). CONCLUSION: Haemodynamic and metabolic parameters
      can be reversed more effectively by VAD than by standard treatment with IABP.
      However, more complications were encountered by the highly invasive procedure and
      by the extracorporeal support.

PMID- 15734772
TI  - A trial of self-adhesive patch electrodes and hand-held paddle electrodes for
      external cardioversion of atrial fibrillation (MOBIPAPA).
AB  - AIMS: External electrical cardioversion is the method of choice to terminate
      persistent atrial fibrillation. Whether the type of shock electrode affects
      cardioversion success is not known. We tested whether hand-held steel electrodes
      improve cardioversion outcome with monophasic or biphasic shocks when compared
      with adhesive patch electrodes. METHODS AND RESULTS: Two hundred and one
      consecutive patients with persistent atrial fibrillation (147 male, mean age 63+/
      1 years, duration of atrial fibrillation 6.3+/-1 months) were randomly assigned
      to cardioversion using either a sinusoidal monophasic or a truncated exponential
      biphasic shock wave form. The first half of patients were cardioverted using
      adhesive patch electrodes, the second half using hand-held steel paddle
      electrodes, and all patients using an anterior-posterior electrode position.
      Paddle electrodes successfully cardioverted 100/104 patients (96%) and patch
      electrodes 85/97 patients (88%, P=0.04). This effect was comparable to that of
      biphasic shocks: biphasic shocks cardioverted 102/104 patients (98%) and
      monophasic shocks 83/97 patients (86%, P=0.001). A beneficial effect of paddle
      electrodes was observed for both shock wave forms. After cross-over from an
      ineffective monophasic to a biphasic shock, cardioversion was successful in
      198/201 (98.5%) patients. Unsuccessful cardioversion after cross-over (3/201
      patients) only occurred with patch electrodes (P=0.07). CONCLUSION: Hand-held
      paddle electrodes increase success of external cardioversion of atrial
      fibrillation in this trial. This increase is of similar magnitude as the increase
      in cardioversion success achieved with biphasic shocks. A combination of biphasic
      shocks, paddle electrodes, and an anterior-posterior electrode position renders
      outcome of external cardioversion almost always successful (104/104 patients in
      this trial).

PMID- 15734773
TI  - Percutaneous approach to a stent-based ventricle to coronary vein bypass (venous
      VPASS): comparison to catheter-based selective pressure-regulated retro-infusion
      of the coronary vein.
AB  - AIMS: Percutaneous stent-based ventricle-to-coronary vein bypass (venous VPASS)
      is a new approach to chronic venous arterialization as a treatment modality in an
      otherwise no option patient with coronary artery disease. In this study, the
      efficacy of venous VPASS was compared with catheter-based selective pressure
      regulated retro-infusion of arterial blood during acute ischaemia. METHODS AND
      RESULTS: In seven pigs, venous VPASS was established using a percutaneous
      ultrasound-guided puncture from the anterior cardiac vein to the left ventricle,
      with subsequent implantation of an ePTFE-covered stent graft. During left
      anterior descending artery (LAD) occlusion, coronary venous pressure in the
      distal anterior cardiac vein increased to 55+/-4 mmHg under conditions of venous
      VPASS compared with 78+/-5 mmHg during selective pressure-regulated retro
      infusion. Significant preservation of regional myocardial function was observed
      during venous VPASS (67+/-6% baseline) and during selective retro-infusion (83+/
      4%) compared with control LAD occlusion (0.4+/-2%). CONCLUSION: Percutaneous
      implantation of a PTFE covered stent (venous VPASS) was feasible and associated
      with significant preservation of regional myocardial function during acute
      ischaemia in pigs at reasonable levels of mean coronary venous pressure to avoid
      tissue damage during chronic application.

PMID- 15734774
TI  - A web-based tool for principal component and significance analysis of microarray
      data.
AB  - We have developed a program for microarray data analysis, which features the
      false discovery rate for testing statistical significance and the principal
      component analysis using the singular value decomposition method for detecting
      the global trends of gene-expression patterns. Additional features include
      analysis of variance with multiple methods for error variance adjustment,
      correction of cross-channel correlation for two-color microarrays, identification
      of genes specific to each cluster of tissue samples, biplot of tissues and
      corresponding tissue-specific genes, clustering of genes that are correlated with
      each principal component (PC), three-dimensional graphics based on virtual
      reality modeling language and sharing of PC between different experiments. The
      software also supports parameter adjustment, gene search and graphical output of
      results. The software is implemented as a web tool and thus the speed of analysis
      does not depend on the power of a client computer. AVAILABILITY: The tool can be
      used on-line or downloaded at http://lgsun.grc.nia.nih.gov/ANOVA/

PMID- 15734775
TI  - Thermo-chemotherapy for intermediate or high-risk recurrent superficial bladder
      cancer patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of combined
      local hyperthermia and intravesical mitomycin-C (MMC) in a selected group of
      patients with intermediate or high-risk recurrent transitional cell carcinoma
      (TCC) of bladder. PATIENTS AND METHODS: Forty-seven patients with multiple or
      recurrent Ta or T1 TCC of the bladder were treated with intravesical MMC and
      local hyperthermia of the bladder wall. Patients were treated with either a
      prophylactic protocol (40 mg MMC) after complete transurethral resection of all
      tumours or with an ablative protocol (80 mg MMC) in patients with viable tumours.
      RESULTS: Thirty-two patients were eligible for analysis. The prophylactic
      protocol was administered to 22 patients. After a mean follow-up of 289 days, 20
      patients (91%) were recurrence free. Two patients (9%) had tumour recurrence
      after a mean period of 431 days. The ablative protocol was administered to 10
      patients. Complete tumour ablation was achieved in eight patients (80%) after a
      mean follow up of 104.5 days. CONCLUSIONS: Our efficacy and safety results
      confirm those reported in previously published studies, suggesting the promising
      value of this combined treatment modality for both prophylactic and ablative
      patients. The ablative protocol offers an alternative therapy for a selected
      patient population for whom no other treatment option exists.

PMID- 15734776
TI  - The significance of skeletal-related events for the health-related quality of
      life of patients with metastatic prostate cancer.
AB  - BACKGROUND: We examined the clinical relevance of skeletal-related events (SREs)
      for health state preferences, pain and health-related quality of life in patients
      with advanced prostate cancer and a history of bone metastases. PATIENTS AND
      METHODS: Data were from a clinical trial of zoledronic acid versus placebo in the
      treatment of SREs associated with advanced prostate cancer metastatic to bone.
      Patients (n=248) were included if they experienced an SRE during the study.
      Outcome measures were assessed at fixed intervals. We used mixed-effects models
      to estimate changes in outcomes after each patient's first SRE. RESULTS: There
      were clinically meaningful and statistically significant declines in physical
      well-being after: radiation and pathologic fractures; functional well-being after
      radiation; and emotional well-being after radiation and pathologic fractures.
      There also were meaningful and significant declines in preference and utility
      scores after radiation and fracture. Pain intensity declined after radiation, but
      not after other SREs; no other pain measure changed substantively. CONCLUSIONS:
      SREs have important and significant effects on measures of health-related quality
      of life in men with prostate cancer. Treatments that prevent SREs may not
      demonstrate corresponding effects on outcomes if the effects of SREs occur
      between scheduled outcome assessments. Implications for trial design are
      discussed.

PMID- 15734777
TI  - Survival for rectal cancer patients and international comparisons.
AB  - BACKGROUND: Population-based cancer registry data are important because they
      reflect routine care, present long-term follow-up, can show differences in
      treatment, outcomes and health care over time, and can be used for comparisons
      between regions and countries. PATIENTS AND METHODS: Details of all cancer
      patients in the Munich region are recorded by the Munich Cancer Registry. Rectal
      cancer patients with an invasive primary tumor diagnosed between 1996 and 1998
      were included in this analysis (n=936). Observed and relative survival are
      presented. Observed survival was also investigated with a Cox proportional
      hazards regression model. RESULTS: Median follow-up time of survivors was 5.7
      years. Five-year relative survival for the whole sample was 62.2%. International
      Union Against Cancer (UICC) stage was the most important prognostic factor in the
      multivariate analysis. Compared with the 1992-1999 Surveillance Epidemiology and
      End Results (SEER) data (62.4%), relative survival for each disease stage and the
      whole sample were very similar. In comparison with other European registries,
      Munich patients had slightly higher survival rates per stage (for example, 5-year
      relative survival in UICC III was 58.3% in Munich, 54.6% in South East
      Netherlands, 33.3% in Modena and 47.4% in Cote d'Or); however, more patients in
      Munich were in higher disease stages with worse prognoses, indicating poorer
      early detection. CONCLUSIONS: These results indicate that treatment of rectal
      cancer in Munich is good, but early detection could be improved. Cancer
      registries should publish their population-based stage data to ensure quality of
      care and provide regular feedback to health-care workers and decision makers.
      Comparisons between countries without stage data should be conducted cautiously.

PMID- 15734779
TI  - Influence of muscle relaxation on neuromonitoring of the recurrent laryngeal
      nerve during thyroid surgery.
AB  - BACKGROUND: The influence of muscle relaxation on the intra-operative
      neuromonitoring of the recurrent laryngeal nerve during thyroid surgery is
      unclear. METHODS: In a prospective study involving 200 patients undergoing
      elective thyroid surgery, the influence of muscle relaxation on neuromonitoring
      of the recurrent laryngeal nerve was investigated. The patients received balanced
      anaesthesia with oxygen-nitrous oxide-isoflurane, and rocuronium bromide was used
      as the non-depolarizing neuromuscular blocking agent. The degree of relaxation
      was monitored continuously by accelerometry [twitch (% TW)]. Summed action
      potentials (SAcP) obtained from the vocalis muscle were characterized by the area
      under the electromyographic curve expressed in millivolt seconds. RESULTS: Evoked
      potentials were obtainable in all patients and at all time points. With
      decreasing neuromuscular blockade a significant increase in the potentials evoked
      at the vocalis muscle was observed. At 0% TW SAcP was 1.27 (SD 1.02) mV s. An
      increase in TW to 10% was accompanied by an increase in SAcP to 2.68 (2.01) mV s
      (P<0.01). At a TW of 25%, mean SAcPs of 5.08 mV s were recorded. CONCLUSIONS:
      There was a significant difference in the degree of relaxation of the adductor
      pollicis muscle and the vocalis muscle. The laryngeal muscles exhibited a shorter
      response time than the adductor pollicis and recovered more quickly. These
      results confirm the feasibility of intra-operative neuromonitoring of the
      recurrent laryngeal nerve during neuromuscular blockade.

PMID- 15734780
TI  - Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation
      and pharmacokinetics?
AB  - BACKGROUND: The development of hydroxyethyl starches (HES) with low impact on
      blood coagulation but higher volume effect compared with the currently used HES
      solutions is of clinical interest. We hypothesized that high molecular weight,
      low-substituted HES might possess these properties. METHODS: Thirty pigs were
      infused with three different HES solutions (20 ml kg(-1)) with the same degree of
      molar substitution (0.42) but different molecular weights (130, 500 and 900 kDa).
      Serial blood samples were taken over 24 h and blood coagulation was assessed by
      Thromboelastograph analysis and analysis of plasma coagulation. In addition,
      plasma concentration and in vivo molecular weight were determined and
      pharmacokinetic data were computed based on a two-compartment model. RESULTS:
      Thromboelastograph analysis and plasma coagulation tests did not reveal a more
      pronounced alteration of blood coagulation with HES 500 and HES 900 compared with
      HES 130. In contrast, HES 500 and HES 900 had a greater area under the plasma
      concentration-time curve [1542 (142) g min litre(-1), P<0.001, 1701 (321) g min
      litre(-1), P<0.001] than HES 130 [1156 (223) g min litre(-1)] and alpha half life
      (t(alpha)(1/2)) was longer for HES 500 [53.8 (8.6) min, P<0.01] and HES 900 [57.1
      (12.3) min, P<0.01] than for HES 130 [39.9 (10.7) min]. Beta half life
      (t(beta)(1/2)), however, was similar for all three types of HES [from 332 (100)
      to 381 (63) min]. CONCLUSIONS: In low-substituted HES, molecular weight is not a
      key factor in compromising blood coagulation. The longer initial intravascular
      persistence of high molecular weight low-substituted HES might result in a longer
      lasting volume effect.

PMID- 15734781
TI  - Differential effects of halothane and isoflurane on lumbar dorsal horn neuronal
      windup and excitability.
AB  - BACKGROUND: Windup of spinal nociceptive neurones may underlie temporal summation
      of pain, influencing the minimum alveolar concentration (MAC) of anaesthetics
      required to prevent movement to supramaximal stimuli. We hypothesized that
      halothane and isoflurane would differentially affect windup of dorsal horn
      neurones. METHODS: We recorded 18 nociceptive dorsal horn neurones exhibiting
      windup to 1 Hz electrical hindpaw stimuli in rats. Effects of 0.8 and 1.2 MAC
      isoflurane and halothane were recorded in the same neurones (counterbalanced,
      crossover design). Windup was calculated as the total number of C-fibre (100-400
      ms latency) plus afterdischarge (400-1000 ms latency) spikes/20 stimuli (area
      under curve, AUC) or absolute windup (C-fibre plus afterdischarge-20 x initial
      response). RESULTS: Increasing isoflurane from 0.8 to 1.2 MAC did not affect AUC,
      but increased absolute windup from 429 (62) to 618 (84) impulses/20 stimuli
      (P<0.05) and depressed the initial C-fibre response from 14 (3) to 8 (2) impulses
      (P<0.05). Increasing halothane from 0.8 to 1.2 MAC depressed AUC from 690 (79) to
      537 (65) impulses/20 stimuli (P<0.05) and the initial response from 18 (2) to 13
      (2) impulses (P<0.05), but absolute windup was not affected. Absolute windup was
      117% greater during 1.2 MAC isoflurane compared with 1.2 MAC halothane.
      CONCLUSIONS: Windup was significantly greater under isoflurane than halothane
      anaesthesia at 1.2 MAC, whereas the initial C-fibre response was suppressed more
      by isoflurane. These findings suggest that these two anaesthetics have
      mechanistically distinct effects on neuronal windup and excitability.

PMID- 15734782
TI  - Effects of AM281, a cannabinoid antagonist, on systemic haemodynamics, internal
      carotid artery blood flow and mortality in septic shock in rats.
AB  - INTRODUCTION: The purpose of this study was to examine the effects of AM281, a
      cannabinoid receptor antagonist, on systemic haemodynamics, internal carotid
      artery blood flow and mortality during septic shock in rats. METHODS: The study
      included three sets of experiments: measurements of changes in systemic
      haemodynamics and left internal carotid artery flow (30 animals divided into
      three groups of 10); measurements of biochemical variables (n=30); assessment of
      mortality (n=30). Male Wistar rats (7 weeks old) were randomly divided into three
      groups: group 1, control; group 2, lipopolysaccharide (LPS) i.v., Escherichia
      coli endotoxin 10.0 mg kg(-1) i.v., bolus; group 3, LPS 10.0 mg kg(-1) i.v.+AM281
      1 mg kg(-1) i.v. Systemic haemodynamics, carotid artery flow changes and
      biochemical variables were assessed at pretreatment and 1, 2 and 3 h after the
      treatment was performed. RESULTS: Administration of AM281 could prevent the
      haemodynamic changes induced by sepsis. Tumour necrosis factor-alpha and
      interleukin 1-beta increased in the LPS i.v. and LPS i.v.+AM281 groups at 1, 2
      and 3 h after treatment; significant differences were observed in these levels in
      the two groups at these times. Internal carotid artery blood flow remained fairly
      constant in the control and LPS i.v.+AM281 groups compared with baseline values.
      In the LPS i.v. group, it decreased at 2 and 3 h after the treatment compared
      with baseline values [at 2 h: control 12.7 (SD 0.9) ml min(-1), LPS i.v. 8.7
      (1.4) ml min(-1) (P<0.05), LPS i.v.+AM281 11.5 (0.9) ml min(-1); at 3 h: control
      12.7 (0.4) ml min(-1), LPS i.v. 7.7 (1.3) ml min(-1) (P<0.05), LPS i.v.+AM281
      11.6 (1.0) ml min(-1)]. Significant differences in mortality within 6 and 12 h
      were found between the LPS i.v. and LPS i.v.+AM281 groups [6 h mortality: LPS
      i.v. 5/10 (50%), LPS i.v.+AM281 2/10 (20%), P<0.05; 12 h mortality: LPS i.v.
      group 10/10 (100%), LPS i.v.+AM281 5/10 (50%), P<0.05]. CONCLUSIONS:
      Administration of AM281 prevented changes in systemic haemodynamic and internal
      carotid artery blood flow and could improve mortality in experimentally induced
      septic shock in rats. These findings may have significant therapeutic
      implications in the treatment of septic shock.

PMID- 15734783
TI  - Use of activated recombinant coagulation factor VII in patients undergoing
      reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum:
      a double-blind, randomized, placebo-controlled trial.
AB  - BACKGROUND: Activated recombinant coagulation factor VII (rFVIIa) effectively
      prevents and controls bleeding in patients with coagulopathy. Data show that
      rFVIIa may reduce blood loss and eliminate the need for transfusion in patients
      with normal haemostasis undergoing major surgery. We assessed the efficacy of
      rFVIIa in patients with normal haemostasis undergoing repair surgery of major
      traumatic fracture of the pelvis or the pelvis and acetabulum, who were expected
      to have a large volume of blood loss. METHODS: We performed a double-blind,
      randomized, placebo-controlled trial involving 48 patients undergoing major
      pelvic-acetabular surgery. Patients were randomized to receive an i.v. bolus
      injection of rFVIIa 90 microg kg(-1) or placebo as add-on therapy at the time of
      the first skin incision. All patients also received intraoperative salvaged red
      blood cells (RBC). RESULTS: There was no significant difference in the total
      volume of perioperative blood loss, the primary outcome variable, between the
      rFVIIa and placebo groups. In addition, there were no differences between the two
      groups in the total volume of blood components, including salvaged RBC
      transfused, number of patients requiring allogeneic blood components, total
      volume of fluids infused, total operating time, time taken after entry to the
      intensive care unit to reach normal body temperature and acid-base status, and
      time spent in hospital. No adverse events, in particular thromboembolic events,
      were reported in either group. CONCLUSIONS: In patients with normal haemostasis
      undergoing repair surgery of traumatic pelvic-acetabular fracture, the
      prophylactic use of rFVIIa does not decrease the volume of perioperative blood
      loss.

PMID- 15734784
TI  - Laryngospasm during subarachnoid block.
AB  - Central neuraxial block is associated with increased vagal tone. We report a
      patient who developed laryngospasm and stridor under spinal anaesthesia. This was
      treated successfully with i.v. atropine and fluids. We propose that the
      laryngospasm was secondary to increased vagal tone under the spinal anaesthetic.
      Such a manifestation of increased vagal tone under spinal anaesthesia has not
      been reported previously.

PMID- 15734785
TI  - Relationship between bispectral index, electroencephalographic state entropy and
      effect-site EC50 for propofol at different clinical endpoints.
AB  - BACKGROUND: State entropy (SE) is a newly available monitor for depth of
      anaesthesia. We investigated whether the relationship between predicted effect
      site propofol concentration and both bispectral index (BIS) and SE values is
      useful for predicting loss of verbal contact and loss of consciousness during
      steady-state conditions. METHODS: Twenty unpremedicated patients undergoing
      elective major abdominal surgery were recruited. A target-controlled infusion of
      propofol was administered using Schneider's pharmacokinetic model. The propofol
      infusion was set at an initial site-effect concentration of 1.0 microg ml(-1),
      and increased by 1.0 microg ml(-1) steps every 4 min, up to 6.0 microg ml(-1). A
      4-min interval was chosen to ensure that steady-state site-effect concentrations
      were obtained. Propofol site-effect concentrations and BIS and SE values were
      recorded at loss of verbal contact (LVC) and loss of consciousness (LOC).
      Population values for predicted effect-site concentrations at the clinical
      endpoints were estimated and correlated with BIS and SE values. RESULTS: For LVC,
      the effect-site concentration for 90% of patients was 1.1 (1.1-3.2) microg ml(-1)
      and for LOC 2.8 (2.8-5.65) microg ml(-1). LVC occurred in 90% of patients at a
      BIS value of 70.2 (70.2-90.2) and an SE value of 60.3 (60.3-75.5) and LOC
      occurred at a BIS value of 38.2 (38.2-70.4) and an SE value of 42.2 (42.2-60.4).
      CONCLUSIONS: LVC and LOC occurred within a defined range of predicted effect-site
      concentrations. SE had a smaller range than BIS and higher correlation with
      effect-site concentration and may be more useful than BIS in predicting both LVC
      and LOC.

PMID- 15734786
TI  - Performance of breathing filters under wet conditions: a laboratory evaluation.
AB  - INTRODUCTION: Heat and moisture exchangers in combination with a bacterial and
      viral filter (HMEF) are widely used during general anaesthesia. Excess patient
      secretions occluding the HMEF have been responsible for previous case reports of
      airway obstruction. A previous study suggested that differences in HMEF design
      might contribute to filter obstruction under wet conditions. METHODS: We tested
      14 types of HMEF under wet conditions to establish which design features
      contributed to HMEF obstruction. Incremental amounts of saline were added to each
      filter. The pressure across the filter was measured with an air flow of 60 litre
      min(-1). RESULTS: We observed that saline added to the filter was often not
      easily visible to the casual observer. This concealment volume varied between
      filters. Ceramic hydrophobic pleated-membrane filters did not absorb saline and
      their resistance did not change. The composite filter where the moisture exchange
      component was either polyurethane foam or cellulose absorbed saline and
      contributed to a rise in resistance of 70-480% with the higher value more typical
      of the cellulose-paper-based HMEF. CONCLUSION: The ideal HMEF for use during
      general anaesthesia should prevent the passage of viral, bacterial and prion
      material, should provide this filtration performance even under wet conditions,
      should supplement humidification of the inspired air and anaesthetic gases and
      should not increase respiratory work. We have identified large variations in HMEF
      performance under wet conditions. Users should be aware of performance variation
      in HMEFs and use a filter suited to the intended application.

PMID- 15734787
TI  - PPARgamma agonists inhibit TGF-beta induced pulmonary myofibroblast
      differentiation and collagen production: implications for therapy of lung
      fibrosis.
AB  - Pulmonary fibrosis is a progressive life-threatening disease for which no
      effective therapy exists. Myofibroblasts are one of the key effector cells in
      pulmonary fibrosis and are the primary source of extracellular matrix production.
      Drugs that inhibit the differentiation of fibroblasts to myofibroblasts have
      potential as antifibrotic therapies. Peroxisome proliferator-activated receptor
      (PPAR)-gamma is a transcription factor that upon ligation with PPARgamma agonists
      activates target genes containing PPAR response elements. PPARgamma agonists have
      anti-inflammatory activities and may have potential as antifibrotic agents. In
      this study, we examined the abilities of PPARgamma agonists to block two of the
      most important profibrotic activities of TGF-beta on pulmonary fibroblasts:
      myofibroblast differentiation and production of excess collagen. Both natural
      (15d-PGJ2) and synthetic (ciglitazone and rosiglitazone) PPARgamma agonists
      inhibited TGF-beta-driven myofibroblast differentiation, as determined by alpha
      smooth muscle actin-specific immunocytochemistry and Western blot analysis.
      PPARgamma agonists also potently attenuated TGF-beta-driven type I collagen
      protein production. A dominant-negative PPARgamma partially reversed the
      inhibition of myofibroblast differentiation by 15d-PGJ2 and rosiglitazone, but
      the irreversible PPARgamma antagonist GW-9662 did not, suggesting that the
      antifibrotic effects of the PPARgamma agonists are mediated through both
      PPARgamma-dependent and independent mechanisms. Thus PPARgamma agonists have
      novel and potent antifibrotic effects in human lung fibroblasts and may have
      potential for therapy of fibrotic diseases in the lung and other tissues.

PMID- 15734788
TI  - Expression and localization of diacylglycerol kinase isozymes and enzymatic
      features in rat lung.
AB  - Diacylglycerol kinase (DGK) catalyzes phosphorylation of diacylglycerol to
      generate phosphatidic acid, and both molecules are known to serve as second
      messengers as well as important intermediates for the synthesis of various
      lipids. In this study, we investigated the spatiotemporal expression patterns of
      DGK isozymes together with the developmental changes of the mRNA expression and
      enzymatic property in rat lung. Northern blot and RT-PCR analyses showed that
      mRNAs for DGKalpha, -epsilon, and -zeta were detected in the lung. By
      immunohistochemical examination, DGKalpha and -zeta were shown to be coexpressed
      in alveolar type II cells and macrophages. Interestingly, these isozymes were
      localized at distinct subcellular locations, i.e., DGKalpha in the cytoplasm and
      DGKzeta in the nucleus, suggesting different roles for these isozymes. In the
      developing lung, the expression for DGKalpha and -zeta was transiently elevated
      on embryonic day 21 (E21) to levels approximately two- to threefold higher than
      on postnatal day 0 (P0). On the other hand, the expression for DGKepsilon was
      inversely elevated approximately twofold on P0 compared with that on E21. These
      unique changes in the expression pattern during the perinatal period suggest that
      each isozyme may play a distinct role in the adaptation of the lung to air or
      oxygen breathing at birth.

PMID- 15734789
TI  - Lung infection with gamma-herpesvirus induces progressive pulmonary fibrosis in
      Th2-biased mice.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic lung disease of
      unknown etiology. A viral pathogenesis in IPF has been suggested since >95% of
      IPF patients have evidence of chronic pulmonary infection with one or more
      herpesviruses. To determine whether pulmonary infection with herpesvirus can
      cause lung fibrosis, we infected mice with the murine gamma-herpesvirus 68
      (MHV68). Because IPF patients have a T helper type 2 (Th2) pulmonary phenotype,
      we used IFN-gammaR-/-, a strain of mice biased to develop Th2 responses. Chronic
      MHV68 infection of IFN-gammaR-/- mice resulted in progressive deposition of
      interstitial collagen as shown by light and electron microscopy. A significant
      decrease in tidal volume paralleled the collagen deposition. Five features
      typically seen in IPF, increased transforming growth factor-beta expression,
      myofibroblast transformation, production of Th2 cytokines, hyperplasia of type II
      cells, and increased expression of matrix metalloproteinase-7, were also present
      in chronically infected IFN-gammaR-/- mice. There also was altered synthesis of
      surfactant proteins, which is seen in some patients with familial IPF. MHV68
      viral protein was found in type II alveolar epithelial cells, especially in lung
      areas with extensive alveolar remodeling. In summary, chronic herpesvirus
      pulmonary infection in IFN-gammaR-/- mice causes progressive pulmonary fibrosis
      and many of the pathological features seen in IPF.

PMID- 15734790
TI  - Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway
      neutrophilia and inflammatory mediators through an NF-kappaB-independent
      mechanism.
AB  - Consumption of a naturally occurring polyphenol, resveratrol, in particular
      through drinking moderate amounts of red wine, has been suggested to be
      beneficial to health. A plethora of in vitro studies published demonstrate
      various anti-inflammatory actions of resveratrol. The aim of this research was to
      determine whether any of these anti-inflammatory effects translate in vivo in a
      rodent model of LPS induced airway inflammation. Resveratrol reduced lung tissue
      neutrophilia to a similar magnitude as that achieved by treatment with
      budesonide. This was associated with a reduction in pro-inflammatory cytokines
      and prostanoid levels. Interestingly, the reduction did not appear to be due to
      an impact on NF-kappaB activation or the expression of the respective genes as
      suggested by various in vitro publications. These results suggest that
      resveratrol may possess anti-inflammatory properties via a novel mechanism.
      Elucidation of this mechanism may lead to potential new therapies for the
      treatment of chronic inflammation.

PMID- 15734791
TI  - Prednisolone-induced changes in dystrophic skeletal muscle.
AB  - Although glucocorticoids delay the progression of Duchenne muscular dystrophy
      (DMD) their mechanism of action is unknown. Skeletal muscle gene expression
      profiles of mdx mice, an animal model of DMD, treated with prednisolone were
      compared with control mice at 1 and 6 wk. Of the 89 early differentially
      regulated genes and ESTs, delta-sarcoglycan, myosin Va, FK506-binding protein 51
      (FKBP51), the potassium channel regulator potassium inwardly-rectifying channel
      Isk-like (IRK2) and ADAM 10 were overexpressed, whereas growth hormone-releasing
      hormone receptor (GHRHR) and Homer-2 were underexpressed. The 58 late
      differentially overexpressed genes included kallikreins (13, 16, and 26), FKBP51,
      PI3K alpha regulatory subunit, and IGFBP6, while underexpressed genes included
      NeuroD and nicotinic cholinergic receptor gamma. At both time points,
      overexpression of a cohort of genes relating to metabolism and proteolysis was
      apparent, alongside the differential expression of genes relating to calcium
      metabolism. Treatment did not increase muscle regeneration, reduce the number of
      infiltrating macrophages, or alter utrophin expression or localization. However,
      in the treated mdx soleus muscle, the percentage of slow fibers was significantly
      lower compared with untreated controls after 6 wk of treatment. These results
      show that glucocorticoids confer their benefit to dystrophic muscle in a complex
      fashion, culminating in a switch to a more normal muscle fiber type.

PMID- 15734792
TI  - Gating of aquaporins by low temperature in roots of chilling-sensitive cucumber
      and chilling-tolerant figleaf gourd.
AB  - Effects of low temperature (8 degrees C) on the hydraulic conductivity of young
      roots of a chilling-sensitive (cucumber, Cucumis sativus L.) and a chilling
      resistant (figleaf gourd, Cucurbita ficifolia Bouche) crop have been measured at
      the levels of whole root systems (root hydraulic conductivity, Lp(r)) and of
      individual cortical cells (cell hydraulic conductivity, Lp). Exposure of roots to
      low temperature (LRT) for up to 6 d caused a stronger suberization of the
      endodermis in cucumber compared with figleaf gourd, but no development of
      exodermal Casparian bands in either species. Changes in anatomy after 6 d of LRT
      treatment corresponded with a reduction in hydrostatic root Lp(r) of cucumber
      roots by a factor of 24, and by a factor of 2 in figleaf gourd. In figleaf gourd,
      there was a reduction only in hydrostatic Lp(r) but not in osmotic Lp(r)
      suggesting that the activity of water channels was not much affected by LRT
      treatment in this species. Changes in cell Lp in response to chilling and
      recovery were similar to the root levels, although they were more intense at the
      root level. Activation energies (E(a)) and Q10 of water flow as measured at the
      cell level were high in cucumber (E(a)=109+/-13 kJ mol(-1); Q(10)=4.8+/-0.7; n=6
      10 cells), but small in figleaf gourd (E(a)=11+/-2 kJ mol(-1); Q10=1.2+/-0.1; n=6
      10 cells). Roots of figleaf gourd recovered better from LRT treatment than those
      of cucumber. In figleaf gourd, recovery (at both the root and cell level) often
      resulted in Lp and Lp(r) values which were even bigger than the original, i.e.
      there was an overshoot in hydraulic conductivity. These effects were larger for
      osmotic (representing the cell-to-cell passage of water) than for hydrostatic
      Lp(r). After a short-term (1 d) exposure to 8 degrees C followed by 1 d at 20
      degrees C, hydrostatic Lp(r) of cucumber nearly recovered and that of figleaf
      gourd still remained higher due to the overshoot. By contrast, osmotic Lp(r) and
      cell Lp in both species remained high by a factor of 3 compared with the control,
      possibly due to an increased activity of water channels. After preconditioning of
      roots at LRT, increased hydraulic conductivity was completely inhibited by HgCl2
      at both the root and cell levels. Different from figleaf gourd, recovery from
      chilling was not complete in cucumber after longer exposure to LRT. It is
      concluded that at LRT, both changes in the activity of aquaporins (AQPs) and
      alterations of root anatomy determine the water uptake in both species. The high
      temperature dependence of cell Lp in cucumber suggests conformational changes of
      AQPs during LRT treatment which result in channel closure and in a strong gating
      of AQP activity by low temperature. This mechanism is thought to be different
      from that in figleaf gourd where AQPs reacted in the conventional way, i.e. low
      temperature affected the mobility of water molecules in AQPs rather than their
      open/closed state, and Q(10) was low.

PMID- 15734793
TI  - Impact of alphaENaC polymorphisms on the risk of ischemic cerebrovascular events:
      a multicenter case-control study.
AB  - BACKGROUND: Amiloride-sensitive epithelial sodium channels (ENaCs) are important
      candidates in the development of hypertension, which is a major risk factor for
      stroke. Two single-nucleotide polymorphisms (SNPs) in the gene that encodes the
      ENac alpha-subunit (alphaENaC) have been identified. We evaluated those SNPs for
      a possible association with ischemic cerebrovascular events (ICEs). METHODS AND
      RESULTS: We genotyped 1399 patients with ICEs [median age, 70 years;
      interquartile range, 58-78 years; 745 (53%) men] and 1076 control individuals
      without vascular disease [47 (39-58) years; 557 (52%) men] for the SNPs Trp493Arg
      and Ala663Thr. The SNP frequencies at nucleotide 3977 (Trp493Arg) in the
      alphaENaC gene were significantly different in patients and controls. Carriers of
      493Arg had a 1.78-fold increased risk (95% confidence interval, 1.02-3.12) for
      ICEs compared with Trp/Trp carriers. Interaction analysis revealed that the
      relative risk was even higher in women in the lowest age tertile [adjusted odds
      ratio, 3.26 (1.10-9.72)]. CONCLUSIONS: Carriers of the 493Arg allele are at
      increased risk for ICEs compared with Trp/Trp carriers. The effect is independent
      of traditional vascular risk factors and is particularly evident in younger
      women. The Trp493Arg variant in alphaENaC may represent an important candidate
      genetic susceptibility factor in the development of ICEs.

PMID- 15734794
TI  - Assessment of a reference procedure to collect and analyze glucose in capillary
      whole blood.

PMID- 15734795
TI  - The cytokine activity of HMGB1.
AB  - High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein
      present in the nuclei and cytoplasm of nearly all cell types. We recently
      discovered that HMGB1 is secreted into the extracellular milieu and acts as a
      proinflammatory cytokine. Administration of HMGB1 to normal animals causes
      inflammatory responses, including fever, weight loss and anorexia, acute lung
      injury, epithelial barrier dysfunction, arthritis, and death. Anti-HMGB1
      treatment, with antibodies or specific antagonists, rescues mice from lethal
      endotoxemia or sepsis and ameliorates the severity of collagen-induced arthritis
      and endotoxin-induced lung injury. Here, we give an abridged review of the
      cytokine activity of HMGB1, its secretion and release into the extracellular
      milieu, the putative signal transduction pathways, including interaction with
      cell-surface receptors and intracellular signaling, and its role in several
      inflammatory diseases. Finally, the therapeutic potential of blocking HMGB1 in
      the treatment of inflammatory diseases is discussed.

PMID- 15734796
TI  - Termites assess wood size by using vibration signals.
AB  - Contrary to the common perception that termites are indiscriminant eaters,
      termites choose their food carefully; however, the methods by which they choose
      food are not well understood. Using choice experiments and recordings of termites
      feeding on wooden blocks of different sizes, we show that worker drywood termites
      (Cryptotermes domesticus) use the resonant frequency of a block of wood to assess
      its size. Drywood termites showed differences in their response to vibration
      recordings of termites compared with artificially generated signals, suggesting
      that they can discriminate the source of vibration. Furthermore, fewer workers
      matured into neotenic reproductives when recorded termite signals were played,
      suggesting that vibration signals play an important role in termite
      communication.

PMID- 15734797
TI  - Coupling of the cortical hemodynamic response to cortical and thalamic neuronal
      activity.
AB  - Accurate interpretation of functional MRI (fMRI) signals requires knowledge of
      the relationship between the hemodynamic response and the neuronal activity that
      underlies it. Here we address the question of coupling between pre- and
      postsynaptic neuronal activity and the hemodynamic response in rodent
      somatosensory (Barrel) cortex in response to single-whisker deflection. Using
      full-field multiwavelength optical imaging of hemoglobin oxygenation and
      electrophysiological recordings of spiking activity and local field potentials,
      we demonstrate that a point hemodynamic measure is influenced by neuronal
      activity across multiple cortical columns. We demonstrate that the hemodynamic
      response is a spatiotemporal convolution of the neuronal activation. Therefore,
      positive hemodynamic response in one cortical column might be explained by
      neuronal activity not only in that column but also in the neighboring columns.
      Thus, attempts at characterizing the neurovascular relationship based on point
      measurements of electrophysiology and hemodynamics may yield inconsistent
      results, depending on the spatial extent of neuronal activation. The finding that
      the hemodynamic signal observed at a given location is a function of
      electrophysiological activity over a broad spatial region helps explain a
      previously observed increase of local vascular response beyond the saturation of
      local neuronal activity. We also demonstrate that the oxy- and total-hemoglobin
      hemodynamic responses can be well approximated by space-time separable functions
      with an antagonistic center-surround spatial pattern extending over several
      millimeters. The surround "negative" hemodynamic activity did not correspond to
      observable changes in neuronal activity. The complex spatial integration of the
      hemodynamic response should be considered when interpreting fMRI data.

PMID- 15734801
TI  - Generation X: implications for faculty recruitment and development in academic
      health centers.
AB  - Differences and tensions between the Baby Boom generation (born 1945-1962) and
      Generation X (born 1963-1981) have profound implications for the future of
      academic medicine. By and large, department heads and senior faculty are Boomers;
      today's residents and junior faculty are Generation X'ers. Looking at these
      issues in terms of the generations involved offers insights into a number of
      faculty development challenges, including inadequate and inexpert mentoring, work
      life conflicts, and low faculty morale. These insights suggest strategies for
      strengthening academic medicine's recruitment and retention of Generation X into
      faculty and leadership roles. These strategies include (1) improving career and
      academic advising by specific attention to mentoring "across differences"--for
      instance, broaching the subject of formative differences in background during the
      initial interaction; adopting a style that incorporates information-sharing with
      engagement in problem solving; offering frequent, frank feedback; and refraining
      from comparing today to the glories of yesterday; to support such improvements,
      medical schools should recognize and evaluate mentoring as a core academic
      responsibility; (2) retaining both valued women and men in academic careers by
      having departments add temporal flexibility and create and legitimize less-than
      full-time appointments; and (3) providing trainees and junior faculty with ready
      access to educational sessions designed to turn their "intellectual capital" into
      "academic career capital."Given the trends discussed in this article, such
      supports and adaptations are indicated to assure that academic health centers
      maintain traditions of excellence.

PMID- 15734798
TI  - Cardiac stem cells delivered intravascularly traverse the vessel barrier,
      regenerate infarcted myocardium, and improve cardiac function.
AB  - The ability of cardiac stem cells (CSCs) to promote myocardial repair under
      clinically relevant conditions (i.e., when delivered intravascularly after
      reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary
      occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries
      via a catheter positioned into the aortic root. Echocardiographic analysis showed
      that injection of CSCs attenuated the increase in left ventricular (LV) end
      diastolic dimensions and impairment in LV systolic performance at 5 weeks after
      myocardial infarction. Pathologic analysis showed that treated hearts exhibited a
      smaller increase in LV chamber diameter and volume and a higher wall thickness-to
      chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial
      regeneration, decreasing infarct size by 29%. A diploid DNA content and only two
      chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did
      not contribute to tissue reconstitution. In conclusion, intravascular injection
      of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and
      ameliorates LV function. This study demonstrates that CSCs are effective when
      delivered in a clinically relevant manner, a clear prerequisite for clinical
      translation, and that these beneficial effects are independent of cell fusion.
      The results establish CSCs as candidates for cardiac regeneration and support an
      approach in which the heart's own stem cells could be collected, expanded, and
      stored for subsequent therapeutic repair.

PMID- 15734802
TI  - Strategies for defining financial benchmarks for the research mission in academic
      health centers.
AB  - Valid financial benchmarks are needed for the research mission in academic health
      centers (AHCs). Databases listing institutional success in obtaining sponsored
      research funding are publicly available. However, these databases are generally
      not adjusted for AHC size, confounding useful comparisons between institutions.
      The authors suggest simple strategies, which depend on a form of ratio analysis,
      to circumvent this limitation. Annual rates of growth (rates of return, R(f)) are
      determined for total National Institutes of Health research grant dollars, number
      of research grants, and average dollars per research grant for 15 U.S. AHCs.
      Selected institutions are compared to one another and to the total pool of
      medical school funding. Performance is evaluated over a ten-year period (1992
      2001) to illustrate the advantages, limitations, and applications of the ratio
      analysis approach. Alternative strategies are suggested for individual AHCs to
      evaluate their departmental and organizational performance, again without regard
      to institution size, and also dependent on ratios. Application of these
      strategies, especially when individualized to the particular AHC, permits more
      accurate assessment of past performance and more accurate and effective planning
      for future growth.

PMID- 15734803
TI  - A strategy for allocating central funds to support new faculty recruitment.
AB  - Requests for central funding for recruiting new faculty in academic health
      centers (AHCs) typically exceed available resources. The administration's
      prioritization of the requests, therefore, involves implicit or explicit
      predictions of the value of the potential faculty member to the institution.
      Optimal management dictates that the value of the recruit be assessed both on the
      extent to which they contribute to the organization's mission and on their
      capacity to generate revenues. The first premise of this article is that faculty
      recruits can be considered as "projects," and their potential value to the
      organization can be estimated in this context. The second premise is that the
      best way to determine a project's financial worth is by determining the net
      present value of each potential faculty recruit. The author models the
      combination of these premises and demonstrates that the approach allows for the
      more systematic prioritization of resource allocation for faculty recruitment in
      AHCs.

PMID- 15734804
TI  - A theoretical, practical, predictive model of faculty and department research
      productivity.
AB  - PURPOSE: Although numerous characteristics impact faculty research productivity,
      and although researchers have suggested comprehensive theoretical models to
      explain the relationship between these characteristics and levels of faculty
      research productivity, few studies have assessed these models. This study tests
      the ability of the Bland et al. (2002) model-based on individual, institutional,
      and leadership variables influencing faculty research productivity-to explain
      individual and group (department) research productivity within the context of a
      large medical school. METHOD: This study used data from a University of Minnesota
      Medical School-Twin Cities vitality survey conducted in 2000 that had a response
      rate of 76% (n = 465 faculty). A statistical software package was used to conduct
      t tests, logistic regressions, and multiple regressions on these data. RESULTS:
      The validity of faculty, department, and leadership characteristics identified in
      the Bland et al. (2002) model were confirmed as necessary for high levels of
      research productivity. Faculty productivity was influenced more by individual and
      institutional characteristics; group productivity was more affected by
      institutional and leadership characteristics. CONCLUSION: The characteristics and
      groupings (individual, institutional, and leadership) in the Bland et al. (2002)
      model predict faculty research productivity. Research productivity is influenced
      by the interaction of the three broad groupings, and it is the dynamic interplay
      of individual and institutional characteristics, supplemented with effective
      leadership, that determines the productivity of individuals and departments.

PMID- 15734805
TI  - Publications and extramural activities of general internal medicine and medicine
      subspecialty clinician-educators: a multicenter study.
AB  - PURPOSE: Generalist clinician-educators may have more difficulty than specialists
      satisfying common promotion criteria (peer-reviewed publication and extramural
      reputation). This study compared publication rates and participation in
      extramural activities among subspecialist and generalist clinician-educators, and
      sought to determine the views of clinician-educators on the use of publication
      and reputation in determining their promotion. METHOD: A cross-sectional
      questionnaire was delivered to 526 clinician-educators identified by the chairs
      at ten randomly selected U.S. medical schools in 2002. RESULTS: A total of 270
      clinician-educators responded. Medicine subspecialist clinician-educators
      reported more peer-reviewed publications than did general internal medicine (GIM)
      faculty (mean 26.4 versus 10.2, p < .003). Independent predictors of having a
      greater number of peer-reviewed publications were subspecialty membership (p <
      .01), less time spent in clinic (p < .01), focus of scholarship (p = .01),
      academic rank (p < .01), higher quartile of National Institutes of Health funding
      received by respondent's department (p < .01), and years on faculty (p = .03). A
      greater proportion of GIM faculty reported spending most of their protected time
      on scholarly activities less amenable to publication (p = .05). A greater
      proportion of subspecialists felt peer-reviewed publication should be required
      for promotion (p < .01), but a minority of both groups felt this should
      necessarily entail original research. CONCLUSION: Subspecialist clinician
      educators generate significantly more peer-reviewed publications than do their
      GIM colleagues. clinician-educators hold diverse views on the role of publication
      and reputation in determining their promotion.

PMID- 15734806
TI  - The research productivity of faculty in family medicine departments at U.S.
      medical schools: a national study.
AB  - PURPOSE: To determine the research productivity of faculty in family medicine
      departments at U.S. medical schools, as well as the individual and environmental
      characteristics and prior socializing experiences predictive of research
      productivity. METHOD: In 2000, a 43-item questionnaire was mailed to 796 faculty
      to obtain descriptive data toward formulating a conceptual model of the research
      productivity of family medicine faculty. Prior to model construction and testing
      through full-model regression, the model's factors were reduced through factor
      analysis. RESULTS: A total of 474 questionnaires (63%) were returned. Eighty
      percent of respondents spent a half-day or less per week on research; on average
      they produced less than one scholarly product per year. Few had research
      experience, nor could identify a research agenda or current research project.
      Mixed messages were perceived related to research, both at institutional and
      disciplinary levels. In testing a conceptual model, psychological and cognitive
      characteristics were most predictive of research productivity, along with time
      spent on research. Psychological and cognitive factors included enhancing
      research skills, establishing a definable research agenda, fostering research
      networks, having multiple research projects underway, maintaining in-depth
      knowledge of a research area, and clearly understanding research expectations for
      promotion and tenure. CONCLUSION: The clinical and academic demands on family
      medicine faculty reduce the likelihood that they will engage in research. These
      demands prevent the development of a critical mass to provide mentorship and
      networking necessary for research productivity. Resources are needed to recruit
      faculty with an interest in research and to provide faculty development in
      research skills, mentorship, and networking.

PMID- 15734807
TI  - Integration of an academic medical center and a community hospital: the Brigham
      and Women's/Faulkner hospital experience.
AB  - Brigham and Women's Hospital (BWH), a major academic tertiary medical center, and
      Faulkner Hospital (Faulkner), a nearby community teaching hospital, both in the
      Boston, Massachusetts area, have established a close affiliation relationship
      under a common corporate parent that achieves a variety of synergistic benefits.
      Formed under the pressures of limited capacity at BWH and excess capacity at
      Faulkner, and the need for lower-cost clinical space in an era of provider risk
      sharing, BWH and Faulkner entered into a comprehensive affiliation agreement.
      Over the past seven years, the relationship has enhanced overall volume,
      broadened training programs, lowered the cost of resources for secondary care,
      and improved financial performance for both institutions. The lessons of this
      relationship, both in terms of success factors and ongoing challenges for the
      hospitals, medical staffs, and a large multispecialty referring physician group,
      are reviewed. The key factors for success of the relationship have been
      integration of training programs and some clinical services, provision of
      complementary clinical capabilities, geographic proximity, clear role definition
      of each institution, commitment and flexibility of leadership and medical staff,
      active and responsive communication, and the support of a large referring
      physician group that embraced the affiliation concept. Principal challenges have
      been maintaining the community hospital's cost structure, addressing cultural
      differences, avoiding competition among professional staff, anticipating the pace
      of patient migration, choosing a name for the new affiliation, and adapting to a
      changing payer environment.

PMID- 15734808
TI  - Adapting postdoctoral training to interdisciplinary science in the 21st century:
      the Cancer Prevention Fellowship Program at the National Cancer Institute.
AB  - Preparing junior scientists for careers in the health sciences has become an
      immense challenge for many reasons, including the emerging demand for
      multidisciplinary approaches to solving problems in the health sciences. For
      those choosing careers in hybrid and interdisciplinary fields, the "traditional"
      postdoctoral training model may not perform well, particularly in light of other
      problems that plague postdoctoral success. New approaches are required. Using the
      interdisciplinary field of cancer prevention as an example, the authors describe
      the Cancer Prevention Fellowship Program (CPFP) of the National Cancer Institute,
      a three-year postdoctoral program of which the goal is to provide its fellows
      with a strong foundation in cancer prevention through education, mentored
      research, and structured professional development training activities that
      emphasize multidisciplinary approaches and leadership skills. Over time, the CPFP
      has incorporated the best aspects of the traditional postdoctoral training model
      with newer training approaches in an effort to overcome existing problems in
      postdoctoral training and to address the additional complexities inherent in
      training those who seek careers in interdisciplinary science. Many aspects of the
      CPFP, including an efficient infrastructure, a dedicated staff, a capacity to
      provide educational activities, and the provision of rich research opportunities,
      may translate well to other postdoctoral programs that face similar issues.

PMID- 15734809
TI  - Learning and cognitive styles in web-based learning: theory, evidence, and
      application.
AB  - Cognitive and learning styles (CLS) have long been investigated as a basis to
      adapt instruction and enhance learning. Web-based learning (WBL) can reach large,
      heterogenous audiences, and adaptation to CLS may increase its effectiveness.
      Adaptation is only useful if some learners (with a defined trait) do better with
      one method and other learners (with a complementary trait) do better with another
      method (aptitude-treatment interaction). A comprehensive search of health
      professions education literature found 12 articles on CLS in computer-assisted
      learning and WBL. Because so few reports were found, research from non-medical
      education was also included. Among all the reports, four CLS predominated. Each
      CLS construct was used to predict relationships between CLS and WBL. Evidence was
      then reviewed to support or refute these predictions. The wholist-analytic
      construct shows consistent aptitude-treatment interactions consonant with
      predictions (wholists need structure, a broad-before-deep approach, and social
      interaction, while analytics need less structure and a deep-before-broad
      approach). Limited evidence for the active-reflective construct suggests aptitude
      treatment interaction, with active learners doing better with interactive
      learning and reflective learners doing better with methods to promote reflection.
      As predicted, no consistent interaction between the concrete-abstract construct
      and computer format was found, but one study suggests that there is interaction
      with instructional method. Contrary to predictions, no interaction was found for
      the verbal-imager construct. Teachers developing WBL activities should consider
      assessing and adapting to accommodate learners defined by the wholist-analytic
      and active-reflective constructs. Other adaptations should be considered
      experimental. Further WBL research could clarify the feasibility and
      effectiveness of assessing and adapting to CLS.

PMID- 15734810
TI  - Earl's story.

PMID- 15734811
TI  - ACGME requirements for geriatrics medicine curricula in medical specialties:
      progress made and progress needed.
AB  - In the recent past, most physician visits by older adults were with a primary
      care physician, with less than 40% of ambulatory visits to other specialists.
      Since 1991, that trend has reversed. In 2001, 53% of ambulatory visits by
      patients aged 65 years or older were to nonprimary care specialists. Demographic
      trends and an expanding geriatrics medicine knowledge base require that every
      physician develop skills specific to the care of older adults. There are concerns
      that physicians-in-training are not learning adequate specific geriatrics
      medicine content to prepare them for the rapidly expanding numbers of older
      adults who will be seeking medical care. Training standards to prepare residents
      and fellows for practicing medicine are established by experts in the various
      medical specialties serving on individual residency review committees (RRCs) of
      the Accreditation Council for Graduate Medical Education. In 2002 (with a follow
      up in 2003), the Association of Directors of Geriatric Academic Programs' team at
      the University of Cincinnati School of Medicine's Institute for Health Policy and
      Health Services Research reviewed all 91 nonpediatric specialties' RRC program
      requirements to identify the specific curriculum requirements related to
      geriatrics medicine training. As of 2003, 27 of the 91 RRC-accredited specialties
      have specific geriatrics training requirements; the other 70% of these
      specialties did not specifically mention geriatrics training. Even among the
      specialties with specific geriatrics training requirements, curriculum
      expectations are modest. The geriatrics-specific descriptions within the program
      requirements of the 27 specialties are presented in this article. The authors
      encourage the RRCs for all nonpediatric specialties to update their program
      requirements to ensure that future physicians graduating from their graduate
      medical education programs are adequately prepared to care for older adults.

PMID- 15734812
TI  - Viewpoint: what is the best and most ethical model for the relationship between
      mainstream and alternative medicine: opposition, integration, or pluralism?
AB  - Despite radical improvements in medicine over the past 60 years, patients
      maintain multiple health care pathways that include high utilization of
      unconventional treatments. The authors examine three possible relationships
      between mainstream and alternative medicine: opposition, integration, and
      pluralism. Opposition, the traditional ethical position that the medical
      profession must eradicate unconventional medicine for the good of the patient,
      has withered away. Integration of mainstream and alternative medicine is
      increasingly advocated in tandem with hospital-based programs that amalgamate the
      use of conventional and alternative therapies. While advocates of integrative
      medicine often speak of "evidence-based" complementary and alternative medicine
      (CAM), integration fosters double standards for validating conventional and
      unconventional treatments. Integration also ignores unbridgeable epistemological
      beliefs and practices between mainstream and alternative medicine. Pluralism,
      which has been relatively ignored, calls for cooperation between the different
      medical systems rather than their integration. By recognizing the value of
      freedom of choice in medical options, pluralism is compatible with the principle
      of patient autonomy. Nonetheless, the pluralistic model does not amount to a
      relativistic stance according in which there would be no objective standards for
      comparing the therapeutic merit of conventional and CAM treatments. As an ethical
      model, pluralism realizes that physicians must be prepared to disagree with
      patient choices to pursue alternative therapies, and urge patients not to forgo
      medically indicated treatment. Pluralism encourages cooperation, research, and
      open communication and respect between practitioners despite the possible
      existence of honest disagreement, and preserves the integrity of each of the
      treatment systems involved.

PMID- 15734813
TI  - Teaching death.

PMID- 15734814
TI  - A.D. series: an artistic tribute to my mother.

PMID- 15734816
TI  - Problem-based learning outcomes: the glass half-full.
AB  - PURPOSE: To compare the characteristics and outcome data of students from a
      single institution with a two-track, problem based learning (PBL) and standard
      (STND) curriculum. METHOD: PBL and STND students from nine graduating classes at
      Southern Illinois University School of Medicine were compared using common
      medical school performance outcomes (USMLE Step 1, USMLE Step 2, clerkship mean
      ratings, number of clerkship honors and remediation designations, and the senior
      clinical competency exam), as well as common admission and demographic variables.
      RESULTS: PBL students were older, and the cohort had a higher proportion of
      women. The two tracks had similar USMLE Step 1 and 2 mean scores and pass rates.
      Performance differences were significant for PBL students in two clerkships as
      well as in the clerkship subcategories of clinical performance, knowledge and
      clinical reasoning, and noncognitive behaviors. In addition, the proportion of
      PBL students earning honors was greater. CONCLUSIONS: The traditional
      undergraduate educational outcomes for the PBL and STND students are very
      positive. In several of the clerkship performance measures, the PBL students
      performed significantly better, and in no circumstance did they perform worse
      than the STND students.

PMID- 15734817
TI  - A snapshot of the status of problem-based learning in U. S. medical schools, 2003
      04.
AB  - PURPOSE: Although the use of problem-based learning (PBL) is widespread in U.S.
      medical schools, its true prevalence is unknown. This study examined the
      prevalence of PBL in preclinical curricula. METHOD: In 2003, a Web-based
      questionnaire was sent to education deans or directors of medical education at
      the 123 Liaison Committee on Medical Education-accredited medical schools in the
      United States. The respondents indicated whether or not they were using PBL and
      what percentage of faculty-student contact hours in the preclinical years used
      PBL. RESULT: All 123 schools responded. Of them, 70% used PBL in the preclinical
      years. Of schools using PBL, 45% used it for less than 10% of their formal
      teaching, while 6% used it for more than half of their formal teaching. Of the
      30% of schools not using PBL, 22% had used it in the past, and 2% had plans to
      incorporate it in the future. CONCLUSIONS: Use of PBL is widespread in the
      preclinical curricula of U.S. medical schools. That use is limited, however,
      since fewer than 6% of programs use it for more than 50% of their instruction.

PMID- 15734818
TI  - Interns' participation and learning in clinical environments in a New Zealand
      hospital.
AB  - PURPOSE: To explore factors that encourage interns to participate actively within
      clinical rotations. Encouraging their participation in workplace interactions and
      activities during their clinical rotations is central to effective development of
      clinical practice. METHOD: In 2002-03, individual interviews and a focus group
      were conducted to gather data about interns' experiences in clinical rotations
      within a New Zealand hospital setting. A model for planning and organizing
      clinical learning was drafted and refined by iteration with other learners and
      more experienced peers. RESULTS: The findings resulted in a model for
      participation in clinical settings where two critical components were identified:
      the tasks of patient care and engagement with the clinical team. These two
      components are further divided into two aspects: initiation and maintenance. The
      outcome of all four factors working well is a reinforcing cycle of activities
      that promote and encourage effective participation and learning. CONCLUSION: This
      model could provide a framework and best-practice guide that could be used for
      faculty development and thereby allow both supervisors and learners to gain
      confidence and satisfaction.

PMID- 15734819
TI  - The dependability of medical students' performance ratings as documented on in
      training evaluations.
AB  - PURPOSE: To demonstrate an approach to obtain an unbiased estimate of the
      dependability of students' performance ratings during training, when the data
      collection design includes nesting of student in rater, unbalanced nest sizes,
      and dependent observations. METHOD: In 2003, two variance components analyses of
      in-training evaluation (ITE) report data were conducted using urGENOVA software.
      In the first analysis, the dependability for the nested and unbalanced data
      collection design was calculated. In the second analysis, an approach using
      multiple generalizability studies was used to obtain an unbiased estimate of the
      student variance component, resulting in an unbiased estimate of dependability.
      RESULTS: Results suggested that there is bias in estimates of the dependability
      of students' performance on ITEs that are attributable to the data-collection
      design. When the bias was corrected, the results indicated that the dependability
      of ratings of student performance was almost zero. CONCLUSION: The combination of
      the multiple generalizability studies method and the use of specialized software
      provides an unbiased estimate of the dependability of ratings of student
      performance on ITE scores for data-collection designs that include nesting of
      student in rater, unbalanced nest sizes, and dependent observations.

PMID- 15734822
TI  - EASEing into the future.

PMID- 15734823
TI  - The development of the EASE model.
AB  - The estimation and assessment of substance exposure (EASE) model has been under
      development and in use since the early 1990s. It is a general model that can be
      used to predict workplace exposure to any substance hazardous to health. The
      current EASE model (version 2.0) has been used widely in the risk assessment of
      new and existing chemicals by the UK Health and Safety Executive (HSE) and other
      regulatory agencies. EASE has also been distributed globally to over 200 users
      and therefore may have been used for many other purposes. Despite widespread use
      of the model, neither the development of its structure nor its underlying
      concepts and principles have been published in the open literature. Using
      surviving documentary evidence and discussions with key personnel, the creation
      and development of the model from 1992 to 2002 is described. The role of the
      HSE's National Exposure Database (NEDB) as the principal data source for the
      development of the model output exposure ranges is described. A number of
      problems and limitations of the model have been identified and the description of
      the model's development provides some explanation of their presence.

PMID- 15734824
TI  - Comparison of measured dermal dust exposures with predicted exposures given by
      the EASE expert system.
AB  - Estimation and Assessment of Substance Exposure (EASE) is a rule-based computer
      expert system used by regulatory authorities within the European Union to assist
      in assessing exposure for both new and existing substances. It can provide
      estimates of both inhalation exposure levels and dermal exposure levels to the
      hands and forearms. This article describes the results of a study in which
      measurements of workplace dermal zinc exposures were collected for an industry
      wide risk assessment and also compared with the levels predicted by EASE.
      Measurements were obtained from subjects in seven different workplaces that were
      producing or working with zinc metal or zinc compounds. The work activities were
      grouped a priori into one of three categories used by EASE for dermal exposure
      assessment: 'non-dispersive use with intermittent direct handling', 'wide
      dispersive use with intermittent direct handling' and 'wide dispersive use with
      extensive direct handling'. The predicted exposure ranges for these categories
      are 0.1-1, 1-5 and 5-15 mg cm(-2) day(-1). Although the average measured exposure
      levels for each of the categories increased in line with the predictions from
      EASE, the model overestimated dermal exposure to the hands by a factor of
      approximately 50 when the mid-point of the EASE range was compared with the
      measured mean exposure. Furthermore, a significant additional exposure was found
      on other parts of the workers' bodies for which EASE does not provide any
      estimates. Interpretation of the dermal exposure data was complicated by the use
      of protective gloves, which might have limited the amount of zinc dust adhering
      to the workers' skin. However, observation of the work activities suggested that
      the pattern of glove use was such that they would not provide a consistent level
      of protection. This study provided an opportunity to collect a large amount of
      dermal zinc exposure data for risk assessment purposes and also enabled a dermal
      sampling method to be developed and assessed. There is no standard method for
      dermal dust exposure measurement, and the choice of method was a key factor in
      the exposure estimation process. With regard to comparison with the EASE
      predictions, it is possible that EASE could appear to perform more accurately if
      its predictions were compared with measurements obtained using surrogate skin
      sampling methods. However, we believe that such sampling can provide a gross
      overestimate of the dust on the skin surface. We suggest that further development
      of the EASE system is necessary to ensure that it better reflects whole-body
      dermal exposures to dusts.

PMID- 15734825
TI  - The validity of the EASE expert system for inhalation exposures.
AB  - Estimation and Assessment of Substance Exposure (EASE) is a computerized expert
      system developed by the UK Health and Safety Executive to facilitate exposure
      assessments in the absence of exposure measurements. The system uses a number of
      rules to predict a range of likely exposures or an 'end-point' for a given work
      situation. The purpose of this study was to identify a number of inhalation
      exposure measurements covering a wide range of end-points in the EASE system to
      compare with the predicted exposures. Occupational exposure data sets were
      identified from previous research projects or from consultancy work. Available
      information for each set of measurements was retrieved from archive storage and
      reviewed to ensure that it was adequate to enable EASE (version 2) predictions to
      be obtained. Exposure measurements and other relevant contextual data were
      abstracted and entered into a computer spreadsheet. EASE predictions were then
      obtained for each task or job and entered into the spreadsheet. In addition, we
      generated a random exposure range for each data set for comparison with the EASE
      predictions. Finally, we produced exposure assessments for a subset of the data
      using a structured subjective assessment method. We were able to identify
      approximately 4000 inhalation exposure measurements covering 52 different
      scenarios and 28 EASE end-points. The data included measurements of solvent
      vapours, non-fibrous dusts and fibres. In 62% of the end-points the EASE
      predictions were generally greater than the exposure measurements and in 30% of
      the end-points the EASE estimates were comparable with the measurements. The
      random allocation of exposure ranges was, as expected, less reliable than EASE,
      although there were still about one-third of the cases where the randomly
      generated exposure ranges generally agreed with the measurements. The structured
      subjective assessments undertaken by a human expert produced exposure estimates
      in better agreement with the measurements with about two-thirds of the end-points
      derived from these assessments in good agreement with the data. We argue that the
      inhalation exposure estimates from EASE could be improved by incorporating some
      of the parameters included in the structured subjective assessment methodology.

PMID- 15734826
TI  - Evaluation and further development of EASE model 2.0.
AB  - EASE (Estimation and Assessment of Substance Exposure) is a general model that
      may be used to predict workplace exposure to a wide range of substances hazardous
      to health. First developed in the early 1990s, it is now in its second Windows
      version. This paper provides a critical assessment of the utility and performance
      of the EASE model, and on the basis of this review, recommendations for the
      structure of a revised model are outlined. Twenty-seven stakeholders were
      interviewed about their previous use of EASE, perceived advantages and
      limitations of the model and suggestions for improvement. A subset of
      stakeholders was contacted on a second occasion to determine their views on the
      preferred outputs for an ideal exposure assessment model. Overall, stakeholders
      felt that the model should be updated to provide more accurate and precise
      exposure assessments. However, users also expressed the view that the simplicity
      and usability of the software model should not be compromised. Six studies
      investigating the validity of the inhalation exposure assessment section of EASE
      were identified. These showed that the model generally either predicted close to
      the measured exposures or overestimated exposure; though performance was highly
      variable. Two studies investigated the validity of the dermal exposure assessment
      and found that EASE produced considerable overestimates of actual dermal exposure
      (the amount of a substance that actually lands on the skin). A conceptual model
      of exposure was developed to investigate whether the structure of the EASE model
      is appropriate. Although EASE has a number of characteristics that describe
      exposure, it is a greatly simplified model and does not include all the important
      exposure determinants. More importantly, EASE can produce estimates of exposure
      that are ambiguous or incomplete. Our conceptual model may provide a rational
      basis for developing an improved version of EASE but further consultation is
      needed to decide the purpose and intended use of any successor to EASE.

PMID- 15734827
TI  - Evaluation of an artificial intelligence program for estimating occupational
      exposures.
AB  - Estimation and Assessment of Substance Exposure (EASE) is an artificial
      intelligence program developed by UK's Health and Safety Executive to assess
      exposure. EASE computes estimated airborne concentrations based on a substance's
      vapor pressure and the types of controls in the work area. Though EASE is
      intended only to make broad predictions of exposure from occupational
      environments, some occupational hygienists might attempt to use EASE for
      individual exposure characterizations. This study investigated whether EASE would
      accurately predict actual sampling results from a chemical manufacturing process.
      Personal breathing zone time-weighted average (TWA) monitoring data for two
      volatile organic chemicals--a common solvent (toluene) and a specialty monomer
      (chloroprene)--present in this manufacturing process were compared to EASE
      generated estimates. EASE-estimated concentrations for specific tasks were
      weighted by task durations reported in the monitoring record to yield TWA
      estimates from EASE that could be directly compared to the measured TWA data. Two
      hundred and six chloroprene and toluene full-shift personal samples were selected
      from eight areas of this manufacturing process. The Spearman correlation between
      EASE TWA estimates and measured TWA values was 0.55 for chloroprene and 0.44 for
      toluene, indicating moderate predictive values for both compounds. For toluene,
      the interquartile range of EASE estimates at least partially overlapped the
      interquartile range of the measured data distributions in all process areas. The
      interquartile range of EASE estimates for chloroprene fell above the
      interquartile range of the measured data distributions in one process area,
      partially overlapped the third quartile of the measured data in five process
      areas and fell within the interquartile range in two process areas. EASE is not a
      substitute for actual exposure monitoring. However, EASE can be used in
      conditions that cannot otherwise be sampled and in preliminary exposure
      assessment if it is recognized that the actual interquartile range could be much
      wider and/or offset by a factor of 10 or more.

PMID- 15734828
TI  - Company-level, semi-quantitative assessment of occupational styrene exposure when
      individual data are not available.
AB  - In epidemiological research, self-reported information about determinants and
      levels of occupational exposures is difficult to obtain, especially if the
      disease under study has a high mortality rate or follow-up has exceeded several
      years. In this paper, we present a semi-quantitative exposure assessment strategy
      for nested case-control studies of styrene exposure among workers of the Danish
      reinforced plastics industry when no information on job title, task or other
      indicators of individual exposure were readily available from cases and controls.
      The strategy takes advantage of the variability in styrene exposure level and
      styrene exposure probability across companies. The study comprised 1522 cases of
      selected malignancies and neurodegenerative diseases and controls employed in 230
      reinforced plastics companies and other related industries. Between 1960 and
      1996, 3057 measurements of styrene exposure level obtained from 191 companies,
      were identified. Mixed effects models were used to estimate expected styrene
      exposure levels by production characteristics for all companies. Styrene exposure
      probability within each company was estimated for all but three cases and
      controls from the fraction of laminators, which was reported by a sample of 945
      living colleagues of the cases and controls and by employers and dealers of
      plastic raw materials. The estimates were validated from a subset of 427 living
      cases and controls that reported their own work as laminators in the industry. We
      computed styrene exposure scores that integrated estimated styrene exposure level
      and styrene exposure probability. Product (boats), process (hand and spray
      lamination) and calendar year period were the major determinants of styrene
      exposure level. Within-company styrene exposure variability increased by calendar
      year and was accounted for when computing the styrene exposure scores. Exposure
      probability estimates based on colleagues' reports showed the highest predictive
      values in the validation test, which also indicated that up to 67% of the workers
      were correctly classified into a styrene-exposed job. Styrene exposure scores
      declined about 10-fold from the 1960s-1990s. This exposure assessment approach
      may be justified in other industries, and especially in industries dominated by
      small companies with simple exposure conditions.

PMID- 15734829
TI  - Dermal exposure to polycyclic aromatic hydrocarbons among road pavers.
AB  - OBJECTIVES: Dermal exposure to polycyclic aromatic hydrocarbons (PAHs) and the
      role of an industrial by-product, coal fly ash, on workers' PAH exposure were
      investigated during stone mastic asphalt (SMA) paving and remixing. METHODS: PAH
      exposure was measured at eight sites during the laying of SMA containing coal fly
      ash or limestone (conventional SMA) as the filler. Six of the surveys were
      carried out during SMA paving and two during remixing of SMA (hot recycling at
      the paving site). Dermal PAH exposure was measured by hand washing (using
      sunflower oil and wiping with Kleenex tissues) before and after the work shift,
      and by placing exposure pads on the workers' wrists during the work shift. The
      analyses included 15 native PAHs from the hand-washing samples determined using
      high-performance liquid chromatography equipped with a two-channel fluorescence
      detector and 16 native PAHs and four methylated PAHs from the exposure pads using
      gas chromatography with mass-selective detection. RESULTS: The PAH results
      obtained using the pad and hand-washing methods (concentrations after the work
      shift) were equivalent and showed a strong correlation (r = 0.757, P < 0.001, N =
      23 for total PAHs). There was a statistically significant difference between pre-
      and post-shift samples as measured by hand washing. The skin contamination by
      PAHs was significantly higher (P < 0.01) during remixing than during SMA paving.
      The variation in PAH contamination on the skin explained more of the variation in
      the excretion of urinary 1-hydroxypyrene and phenanthrols than the variation in
      the respiratory PAH concentrations. CONCLUSIONS: The industrial by-product
      investigated in asphalt, coal fly ash, had no statistically significant effect on
      the workers' dermal PAH exposure. The dermal exposure of paving workers to PAHs
      was higher during remixing than during SMA paving.

PMID- 15734830
TI  - Evaluation of facial features on particle inhalation.
AB  - Computational fluid dynamics (CFD) and numerical investigations of particle
      inhalability and contaminant exposure have used simple geometrical surrogates for
      a breathing human form, but the effect of eliminating facial features has not
      been investigated. In this work, the velocity field and particle aspiration
      associated with two differently shaped mannequins were investigated to determine
      if an elliptical form was sufficient to represent the complexity of fluid flow
      associated with an inhaling human. Laser Doppler anemometry was used to measure
      velocity, and both optical sizing and gravimetric analysis were used to measure
      particle aspiration from an aerosol source. All tests were performed with
      continuous inhalation through the mouth, with the mannequin facing the 0.3 m s(
      1) freestream. Although limitations in the laser Doppler optics prevented
      velocity measurements at distances <11 mm in front of the mannequin mouth
      opening, significant velocity differences were identified up to 20 mm in front of
      the mouth opening. This indicated that facial features affected the flow field
      near the face only. Owing to these differences, particle aspiration was compared
      between mannequins for three different velocity ratio conditions using an aerosol
      source. Even with relatively large variability in the aspirated concentration in
      this study, the aspirated mass concentration was significantly less for the
      anatomical mannequin relative to the elliptical form. Thus, the simplified
      elliptical cylinder does not sufficiently characterize the fluid dynamics near
      the mouth of an inhaling human form at these limited test conditions. Future CFD
      and numerical simulations to investigate human aspiration of particles should
      incorporate the complex features of the human face to investigate adequately
      particle aspiration in low velocity environments.

PMID- 15734831
TI  - Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is
      associated with progression of human urothelial carcinomas.
AB  - Bladder cancer is the fifth most common malignancy in the world and represents
      the second most common cause of death among genitourinary tumors. Current
      prognostic parameters such as grade and stage cannot predict with certainty the
      long-term outcome of bladder cancer, and as a result there is a pressing need to
      identify markers that may predict tumor behavior. Earlier we identified the
      adipocyte fatty acid-binding protein (A-FABP), a small-molecular-mass fatty acid
      binding protein that functions by facilitating the intracellular diffusion of
      fatty acids between cellular compartments as a putative marker of progression
      based on a limited study of fresh bladder urothelial carcinomas (UCs) (Celis, J.
      E., Ostergaard, M., Basse, B., Celis, A., Lauridsen, J. B., Ratz, G. P.,
      Andersen, I., Hein, B., Wolf, H., Orntoft, T. F., and Rasmussen, H. H. (1996)
      Loss of adipocyte-type fatty acid binding protein and other protein biomarkers is
      associated with progression of human bladder transitional cell carcinomas. Cancer
      Res.56, 4782-4790). Here we have comprehensively examined the protein expression
      profiles of a much larger sample set consisting of 153 bladder specimens (46
      nonmalignant biopsies, 11 pTa G1, 40 pTa G2, 10 pTa G3, 13 pT1 G3, 23 pT2-4 G3,
      and 10 pT2-4 G4) by gel-based proteomics in combination with immunohistochemistry
      (IHC) using a peptide-based rabbit polyclonal antibody that reacts specifically
      with this protein. Proteomic profiling showed a striking down-regulation of A
      FABP in invasive lesions, a fact that correlated well with immunohistochemical
      analysis of the same samples. The IHC results were confirmed by using a tissue
      microarray (TMA) containing 2,317 samples derived from 1,849 bladder cancer
      patients. Moreover, we found that the altered expression of A-FABP in invasive
      UCs is not due to deregulated expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma), a trans-activator of A-FABP. Taken together, these
      results provide evidence that deregulation of A-FABP may play a role in bladder
      cancer progression and suggest that A-FABP could have a significant prognostic
      value in combination with other biomarkers.

PMID- 15734832
TI  - A role for sphingolipids in producing the common features of type 2 diabetes,
      metabolic syndrome X, and Cushing's syndrome.
AB  - Metabolic syndrome X and type 2 diabetes share many metabolic and morphological
      similarities with Cushing's syndrome, a rare disorder caused by systemic
      glucocorticoid excess. Pathologies frequently associated with these diseases
      include insulin resistance, atherosclerosis, susceptibility to infection, poor
      wound healing, and hypertension. The similarity of the clinical profiles
      associated with these disorders suggests the influence of a common molecular
      mechanism for disease onset. Interestingly, numerous studies identify ceramides
      and other sphingolipids as potential contributors to these sequelae. Herein we
      review studies demonstrating that aberrant ceramide accumulation contributes to
      the development of the deleterious clinical manifestations associated with these
      diseases.

PMID- 15734834
TI  - Fructose normalizes specific counterregulatory responses to hypoglycemia in
      patients with type 1 diabetes.
AB  - We have previously reported that specific counterregulatory responses to
      hypoglycemia were augmented by an infusion of fructose in nondiabetic humans. We
      hypothesized that this effect was due to the interaction of a "catalytic" dose of
      fructose with the regulatory protein for glucokinase in glucose-sensing cells
      that drive counterregulation. To examine whether fructose could restore
      counterregulatory responses in type 1 diabetic patients with defective
      counterregulation, we performed stepped hypoglycemic clamp studies (5.0, 4.4,
      3.9, and 3.3 mmol/l glucose steps, 50 min each) in eight intensively treated
      patients (HbA(1c) 6.4 +/- 0.7%) on two separate occasions: without (control) or
      with coinfusion of fructose (1.2 mg . kg(-1) . min(-1)). Fructose induced a
      resetting of the glycemic threshold for secretion of epinephrine to higher plasma
      glucose concentrations (from 3.3 +/- 0.1 to 3.9 +/- 0.1 mmol/l; P = 0.001) and
      markedly augmented the increment in epinephrine (by 56%; P < 0.001). The
      amplification of epinephrine responses was specific; plasma norepinephrine,
      glucagon, growth hormone, and cortisol were unaffected. Hypoglycemia-induced
      endogenous glucose production ([3-(3)H]-glucose) rose by 90% (P < 0.001) in the
      fructose studies, compared with -2.0% (NS) in control. In concert, the glucose
      infusion rates during the 3.9- and 3.3-mmol/l steps were significantly lower with
      fructose (2.3 +/- 0.6 and 0.0 +/- 0.0 vs. 5.9 +/- 1.15 and 3.9 +/- 1.0 micromol .
      kg(-1) . min(-1), respectively; P < 0.001 for both), indicating the more potent
      counterregulatory response during fructose infusion. We conclude that infusion of
      fructose nearly normalizes the epinephrine and endogenous glucose production
      responses to hypoglycemia in type 1 diabetic patients with impaired
      counterregulation, suggesting that defects in these responses may be dependent on
      glucokinase-mediated glucose sensing.

PMID- 15734833
TI  - Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and
      hyperglycemia by moderate weight reduction in patients with type 2 diabetes.
AB  - To examine the mechanism by which moderate weight reduction improves basal and
      insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes,
      we used (1)H magnetic resonance spectroscopy to assess intrahepatic lipid (IHL)
      and intramyocellular lipid (IMCL) content in conjunction with hyperinsulinemic
      euglycemic clamps using [6,6-(2)H(2)]glucose to assess rates of glucose
      production and insulin-stimulated peripheral glucose uptake. Eight obese patients
      with type 2 diabetes were studied before and after weight stabilization on a
      moderately hypocaloric very-low-fat diet (3%). The diabetic patients were
      markedly insulin resistant in both liver and muscle compared with the lean
      control subjects. These changes were associated with marked increases in IHL
      (12.2 +/- 3.4 vs. 0.6 +/- 0.1%; P = 0.02) and IMCL (2.0 +/- 0.3 vs. 1.2 +/- 0.1%;
      P = 0.02) compared with the control subjects. A weight loss of only approximately
      8 kg resulted in normalization of fasting plasma glucose concentrations (8.8 +/-
      0.5 vs. 6.4 +/- 0.3 mmol/l; P < 0.0005), rates of basal glucose production (193
      +/- 7 vs. 153 +/- 10 mg/min; P < 0.0005), and the percentage suppression of
      hepatic glucose production during the clamp (29 +/- 22 vs. 99 +/- 3%; P = 0.003).
      These improvements in basal and insulin-stimulated hepatic glucose metabolism
      were associated with an 81 +/- 4% reduction in IHL (P = 0.0009) but no
      significant change in insulin-stimulated peripheral glucose uptake or IMCL (2.0
      +/- 0.3 vs. 1.9 +/- 0.3%; P = 0.21). In conclusion, these data support the
      hypothesis that moderate weight loss normalizes fasting hyperglycemia in patients
      with poorly controlled type 2 diabetes by mobilizing a relatively small pool of
      IHL, which reverses hepatic insulin resistance and normalizes rates of basal
      glucose production, independent of any changes in insulin-stimulated peripheral
      glucose metabolism.

PMID- 15734835
TI  - Increased potency and efficacy of combined phosphorylase inactivation and
      glucokinase activation in control of hepatocyte glycogen metabolism.
AB  - Glucokinase and phosphorylase both have a high control strength over hepatocyte
      glycogen metabolism and are potential therapeutic targets for type 2 diabetes. We
      tested whether combined phosphorylase inactivation and glucokinase activation is
      a more effective strategy for controlling hepatic glycogen metabolism than single
      site targeting. Activation of glucokinase by enzyme overexpression combined with
      selective dephosphorylation of phosphorylase-a by an indole carboxamide that
      favors the T conformation of phosphorylase caused a greater stimulation of
      glycogen synthesis than the sum of either treatment alone. This result is
      explained by the complementary roles of elevated glucose-6-phosphate (G6P; a
      positive modulator) and depleted phosphorylase-a (a negative modulator) in
      activating glycogen synthase and also by synergistic inactivation of
      phosphorylase-a by glucokinase activation and the indole carboxamide.
      Inactivation of phosphorylase-a by the indole carboxamide was counteracted by 5
      aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside, which is metabolized to an
      AMP analog; this effect was reversed by G6P. Our findings provide further
      evidence for the inverse roles of G6P and AMP in regulating the activation state
      of hepatic phosphorylase. It is proposed that dual targeting of glucokinase and
      phosphorylase-a enables improved potency and efficacy in controlling hepatic
      glucose metabolism.

PMID- 15734836
TI  - Calcineurin does not mediate exercise-induced increase in muscle GLUT4.
AB  - Exercise induces a rapid increase in expression of the GLUT4 isoform of the
      glucose transporter in skeletal muscle. One of the signals responsible for this
      adaptation appears to be an increase in cytosolic Ca(2+). Myocyte enhancer factor
      2A (MEF2A) is a transcription factor that is involved in the regulation of GLUT4
      expression. It has been reported that the Ca(2+)-regulated phosphatase
      calcineurin mediates the activation of MEF2 by exercise. It has also been shown
      that the expression of activated calcineurin in mouse skeletal muscle results in
      an increase in GLUT4. These findings suggest that increases in cytosolic Ca(2+)
      induce increased GLUT4 expression by activating calcineurin. However, we have
      obtained evidence that this response is mediated by a Ca(2+)-calmodulin-dependent
      protein kinase. The purpose of this study was to test the hypothesis that
      calcineurin is involved in mediating exercise-induced increases in GLUT4. Rats
      were exercised on 5 successive days using a swimming protocol. One group of
      swimmers was given 20 mg/kg body weight of cyclosporin, a calcineurin inhibitor,
      2 h before exercise. A second group was given vehicle. GLUT4 protein was
      increased approximately 80%, GLUT4 mRNA was increased approximately 2.5-fold,
      MEF2A protein was increased twofold, and hexokinase II protein was increased
      approximately 2.5-fold 18 h after the last exercise bout. The cyclosporin
      treatment completely inhibited calcineurin activity but did not affect the
      adaptive increases in GLUT4, MEF2A, or hexokinase expression. We conclude that
      calcineurin activation does not mediate the adaptive increase in GLUT4 expression
      induced in skeletal muscle by exercise.

PMID- 15734837
TI  - Free fatty acid regulation of glucose-dependent intrinsic oscillatory lipolysis
      in perifused isolated rat adipocytes.
AB  - Free fatty acids (FFAs) and glycerol oscillate in plasma. This study examined
      intrinsic lipolytic oscillations within adipocytes. Rat adipocytes were perifused
      with Krebs-Ringer bicarbonate buffer: 1) +/- 2 mmol/l glucose; 2) +1 micromol/l
      isoproterenol +/- 2 mmol/l glucose; 3) + increasing oleate; and 4) + increasing
      percent BSA. At 2 mmol/l glucose, there were 9 +/- 1 glycerol, FFAs, and lactate
      pulses per hour with a pulse duration of 5 +/- 1 min. Lipolytic stimulation
      caused a 50-80% increase in the amplitude of lipolytic oscillations. Removal of
      glucose caused a 40-70% decrease in the amplitude of lipolytic oscillations and
      disturbed the pulsatility. Exogenous FFAs suppressed lipolysis and oscillatory
      amplitude, possibly because of increased cytosolic long-chain coenzyme A (LC
      CoA). Increasing percent BSA increased stimulated lipolysis and oscillatory
      amplitude, possibly because of decreased intracellular LC-CoA. These data show,
      for the first time, intrinsic lipolytic oscillations, which are glucose dependent
      and modulated by FFAs. We hypothesize that lipolytic oscillations are driven by
      oscillatory glucose metabolism, which leads to oscillatory relief of LC-CoA
      inhibition of triglyceride lipase(s). The results contribute to the understanding
      of physiological and biochemical regulators of lipolysis, such as glucose and
      FFAs. Lipolytic oscillations may be beneficial in the delivery of FFAs to liver,
      pancreas, and other tissues.

PMID- 15734838
TI  - Munc18c heterozygous knockout mice display increased susceptibility for severe
      glucose intolerance.
AB  - The disruption of Munc18c binding to syntaxin 4 impairs insulin-stimulated GLUT4
      vesicle translocation in 3T3L1 adipocytes. To investigate the physiological
      function and requirement for Munc18c in the regulation of GLUT4 translocation and
      glucose homeostasis in vivo, we used homologous recombination to generate Munc18c
      knockout (KO) mice. Homozygotic disruption of the Munc18c gene resulted in early
      embryonic lethality, whereas heterozygous KO mice (Munc18c(-/+)) had normal
      viability. Munc18c(-/+) mice displayed significantly decreased insulin
      sensitivity in an insulin tolerance test and a >50% reduction in skeletal muscle
      insulin-stimulated GLUT4 translocation when compared with wild-type (WT) mice.
      Furthermore, glucose-stimulated insulin secretion was significantly reduced in
      islets isolated from Munc18c(-/+) mice compared with those from WT mice. Despite
      the defects in insulin action and secretion, Munc18c(-/+) mice demonstrated the
      ability to clear glucose to the same level as WT mice in a glucose tolerance test
      when fed a normal diet. However, after consuming a high-fat diet for only 5
      weeks, the Munc18c(-/+) mice manifested severely impaired glucose tolerance
      compared with high-fat-fed WT mice. Taken together, these data suggest that the
      reduction of Munc18c protein in the Munc18c(-/+) mice results in impaired insulin
      sensitivity with a latent increased susceptibility for developing severe glucose
      intolerance in response to environmental perturbations such as intake of a high
      calorie diet rich in fat and carbohydrate.

PMID- 15734839
TI  - Differential utilization of saturated palmitate and unsaturated oleate: evidence
      from cultured myotubes.
AB  - We recently described a primarily reduced palmitate oxidation in myotubes
      established from type 2 diabetic subjects, whereas triacylglycerol (TAG)
      accumulation seemed to be adaptive. However, it is still uncertain whether these
      changes are similar for saturated and unsaturated fatty acids and whether high
      concentrations of glucose and/or insulin may change this picture. Studies of
      palmitic acid and oleic acid metabolism in human myotubes established from
      control and type 2 diabetic subjects under conditions of acute high
      concentrations of insulin and/or glucose may solve these questions. Total oleic
      acid and palmitic acid uptake in myotubes was increased during acute insulin
      stimulation (P < 0.01) but not under acute, high-glucose concentrations, and no
      differences were found between the groups. Type 2 diabetic myotubes expressed a
      reduced palmitic acid oxidation to carbon dioxide (P </= 0.04), whereas oleic
      acid oxidation showed no differences between myotubes from both groups. High
      glucose concentrations decreased oleic acid oxidation (P </= 0.03). Lipid
      distribution was not different in diabetic and control myotubes when palmitic
      acid and oleic acid incorporation into cellular lipids was compared. Myotubes
      that were exposed to palmitic acid showed an increased palmitic acid
      incorporation into diacylglycerol (DAG) and TAG compared with myotubes that were
      exposed to oleic acid (P < 0.05) expressing an increased intracellular free fatty
      acid (FFA) level (P < 0.05). Lipid distribution was not affected by high glucose,
      whereas insulin increased FFAs, DAG, and TAG (P < 0.05). De novo lipid synthesis
      from glucose in both diabetic and control myotubes was of the same magnitude
      independent of glucose and insulin concentrations. These results indicate that
      palmitic acid and oleic acid are utilized in the same pattern in diabetic and
      control myotubes even though palmitic acid oxidation is primarily reduced in
      diabetic cells. Palmitic acid and oleic acid are handled differently by myotubes:
      Palmitic acid seems to accumulate as DAG and TAG, whereas oleic acid accumulates
      as intracellular FFAs. These observations indicate that oleic acid is preferable
      as fatty acid as it accumulates to a lesser extent as DAG and TAG than palmitic
      acid. Neither acute hyperglycemia nor de novo lipid synthesis from glucose seems
      central to the TAG accumulation in obesity or type 2 diabetes.

PMID- 15734840
TI  - The endoplasmic reticulum chaperone improves insulin resistance in type 2
      diabetes.
AB  - To determine the role of the endoplasmic reticulum (ER) in diabetes, Akita mice,
      a mouse model of type 2 diabetes, were mated with either heterozygous knockout
      mice or two types of transgenic mice of 150-kDa oxygen-regulated protein
      (ORP150), a molecular chaperone located in the ER. Systemic expression of ORP150
      in Akita mice improves insulin intolerance, whereas the exclusive overexpression
      of ORP150 in pancreatic beta-cells of Akita mice did not change their glucose
      tolerance. Both an insulin tolerance test and hyperinsulinemic-euglycemic clamp
      revealed that ORP150 enhanced glucose uptake, accompanied by suppression of
      oxidized protein. Furthermore, ORP150 enhanced the insulin sensitivity of
      myoblast cells treated with hydrogen peroxide. These data suggest that ORP150
      plays an important role in insulin sensitivity and is a potential target for the
      treatment of diabetes.

PMID- 15734841
TI  - Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated
      insulin resistance in mice.
AB  - Our aim was to study whether the absence of apolipoprotein (apo) C3, a strong
      inhibitor of lipoprotein lipase (LPL), accelerates the development of obesity and
      consequently insulin resistance. Apoc3(-/-) mice and wild-type littermates were
      fed a high-fat (46 energy %) diet for 20 weeks. After 20 weeks of high-fat
      feeding, apoc3(-/-) mice showed decreased plasma triglyceride levels (0.11 +/-
      0.02 vs. 0.29 +/- 0.04 mmol, P < 0.05) and were more obese (42.8 +/- 3.2 vs. 35.2
      +/- 3.3 g; P < 0.05) compared with wild-type littermates. This increase in body
      weight was entirely explained by increased body lipid mass (16.2 +/- 5.9 vs. 10.0
      +/- 1.8 g; P < 0.05). LPL-dependent uptake of triglyceride-derived fatty acids by
      adipose tissue was significantly higher in apoc3(-/-) mice. LPL-independent
      uptake of albumin-bound fatty acids did not differ. It is interesting that whole
      body insulin sensitivity using hyperinsulinemic-euglycemic clamps was decreased
      by 43% and that suppression of endogenous glucose production was decreased by 25%
      in apoc3(-/-) mice compared with control mice. Absence of apoC3, the natural LPL
      inhibitor, enhances fatty acid uptake from plasma triglycerides in adipose
      tissue, which leads to higher susceptibility to diet-induced obesity followed by
      more severe development of insulin resistance. Therefore, apoC3 is a potential
      target for treatment of obesity and insulin resistance.

PMID- 15734842
TI  - Differential responses of visceral and subcutaneous fat depots to nutrients.
AB  - Increased visceral adiposity is a pivotal component of the metabolic syndrome.
      Differential gene expression patterns of fat-derived peptides (FDPs) in visceral
      fat and subcutaneous fat have been characterized in the fasting state. Here we
      examined whether delivery of nutrients differentially affects the expression of
      FDPs in visceral fat versus subcutaneous fat (in the fed state). We increased the
      rate of glucose flux into adipose tissue of normal rats (n = 16) by hyperglycemia
      or hyperinsulinemia using the clamp technique. Glucose uptake was associated with
      increased expression of FDPs, including resistin ( approximately 5-fold),
      adiponectin ( approximately 2-fold), leptin ( approximately 15-fold), plasminogen
      activating inhibitor-1 ( approximately 10-fold), and angiotensinogen (
      approximately 4-fold) in visceral fat, but markedly less in subcutaneous fat.
      Cytokine expression derived mainly from vascular/stromal/macrophage components of
      adipose tissue was less dramatically increased. Infusion of glucosamine amplified
      the results obtained by increasing glucose uptake into adipose tissue, suggesting
      that flux through the hexosamine biosynthetic pathway may serve as a mechanism
      for "nutrient sensing." Nutrient-dependent expression of FDPs in visceral fat was
      also associated with increased plasma levels of several FDPs. Because a biologic
      sensing pathway can dynamically couple daily food intake to abnormal plasma
      levels of important FDPs, we challenge the practice of obtaining plasma levels
      after fasting to assess risk factors for metabolic syndrome.

PMID- 15734843
TI  - Caveolin-1 expression is essential for proper nonshivering thermogenesis in brown
      adipose tissue.
AB  - Recently, we have shown that loss of caveolin-1 leads to marked alterations in
      insulin signaling and lipolysis in white adipose tissue. However, little is known
      about the role of caveolin-1 in brown adipose tissue (BAT), a tissue responsible
      for nonshivering thermogenesis. Here, we show that caveolin-1 null mice have a
      mildly, yet significantly, decreased resting core body temperature. To
      investigate this in detail, we next subjected the mice to fasting (for 24 h) or
      cold treatment (4 degrees C for 24 h), individually or in combination.
      Interestingly, caveolin-1 null mice showed markedly decreased body temperatures
      in response to fasting or fasting/cold treatment; however, cold treatment alone
      had no effect. In addition, under these conditions caveolin-1 null mice failed to
      show the normal increase in serum nonesterified fatty acids induced by fasting or
      fasting/cold treatment, suggesting that these mice are unable to liberate
      triglyceride stores for heat production. In accordance with these results, the
      triglyceride content of BAT was reduced nearly 10-fold in wild-type mice after
      fasting/cold treatment, but it was reduced only 3-fold in caveolin-1 null mice.
      Finally, electron microscopy of adipose tissue revealed dramatic perturbations in
      the mitochondria of caveolin-1 null interscapular brown adipocytes. Taken
      together, our data provide the first molecular genetic evidence that caveolin-1
      plays a critical functional and structural role in the modulation of
      thermogenesis via an effect on lipid mobilization.

PMID- 15734844
TI  - Long-term graft function of adult rat and human islets encapsulated in novel
      alginate-based microcapsules after transplantation in immunocompetent diabetic
      mice.
AB  - We describe the results of the first study to show that adult rat and human
      islets can be protected against xenogenic rejection in immunocompetent diabetic
      mice by encapsulating them in a novel alginate-based microcapsule system with no
      additional permselective membrane. Nonencapsulated islets lost function within 4
      8 days after being transplanted into diabetic Balb/c mice, whereas transplanted
      encapsulated adult rat or human islets resulted in normoglycemia for >7 months.
      When rat islet grafts were removed 10 and 36 weeks after transplantation, the
      mice became immediately hyperglycemic, thus demonstrating the efficacy of the
      encapsulated islets. The explanted capsules showed only a mild cellular reaction
      on their surface and a viability of >85%, and responded to a glucose stimulus
      with a 10-fold increase in insulin secretion. Furthermore, transplanted mice
      showed a slight decrease in the glucose clearance rate in response to
      intraperitoneal glucose tolerance tests 3-16 weeks after transplantation; after
      16 weeks, the rate remained stable. Similar results were obtained for
      encapsulated human islets. Thus we provide the first evidence of successful
      transplantation of microencapsulated human islets. In conclusion, we have
      developed a novel microcapsule system that enables survival and function of adult
      rat and human islets in immunocompetent mice without immunosuppression for >7
      months.

PMID- 15734845
TI  - Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation
      and function in vivo.
AB  - Pancreatic islet formation is a highly regulated process that is initiated at the
      end of gestation in rodents. Endocrine precursor cells first form within the
      epithelium of duct-like structures and then delaminate from the epithelium,
      migrate, and cluster during the early stages of islet formation. The molecular
      mechanisms that regulate endocrine cell migration and islet formation are not
      well understood. Cell culture studies suggest that matrix metalloproteinases
      (MMPs) 2 and 9 are required for islet formation. To address whether MMP2 and MMP9
      function are essential for endocrine cell migration and islet formation in vivo,
      we analyzed pancreas development in MMP2/MMP9 double-deficient mice. Our results
      show that islet architecture and function are unperturbed in these knockout mice,
      demonstrating that both MMP2 and MMP9 functions are dispensable for islet
      formation and endocrine cell differentiation. Our studies also show that a number
      of other MMPs are expressed at the time islet formation is initiated. This
      observation suggests that other MMPs may substitute for MMP2 and MMP9 loss in
      pancreatic tissue. However, islet formation is unaffected in transgenic mice with
      modified tissue inhibitor of metalloproteinase-1 (TIMP1) levels, suggesting that
      MMP activity may contribute little to islet morphogenesis in vivo.

PMID- 15734846
TI  - Beta-cell secretory dysfunction in the pathogenesis of low birth weight
      associated diabetes: a murine model.
AB  - Low birth weight (LBW) is an important risk factor for type 2 diabetes. We have
      developed a mouse model of LBW resulting from undernutrition during pregnancy.
      Restriction of maternal food intake from day 12.5 to 18.5 of pregnancy results in
      a 23% decrease in birth weight (P < 0.001), with normalization after birth.
      However, offspring of undernutrition pregnancies develop progressive, severe
      glucose intolerance by 6 months. To identify early defects that are responsible
      for this phenotype, we analyzed mice of undernutrition pregnancies at age 2
      months, before the onset of glucose intolerance. Fed insulin levels were 1.7-fold
      higher in mice of undernutrition pregnancies (P = 0.01 vs. controls). However,
      insulin sensitivity was normal in mice of undernutrition pregnancies, with normal
      insulin tolerance, insulin-stimulated glucose disposal, and isolated muscle and
      adipose glucose uptake. Although insulin clearance was mildly impaired in mice of
      undernutrition pregnancies, the major metabolic phenotype in young mice of
      undernutrition pregnancies was dysregulation of insulin secretion. Despite normal
      beta-cell mass, islets from normoglycemic mice of undernutrition pregnancies
      showed basal hypersecretion of insulin, complete lack of responsiveness to
      glucose, and a 2.5-fold increase in hexokinase activity. Taken together, these
      data suggest that, at least in mice, primary beta-cell dysfunction may play a
      significant role in the pathogenesis of LBW-associated type 2 diabetes.

PMID- 15734847
TI  - Overexpression of cyclin D1 in pancreatic beta-cells in vivo results in islet
      hyperplasia without hypoglycemia.
AB  - Cyclin D1 can stimulate proliferation by driving cells from the G1 into the S
      phase of the mammalian cell cycle. Previous animal studies have implicated the G1
      S transition as a key regulatory checkpoint governing the proliferation of
      pancreatic islet cells. We expressed cyclin D1 in the beta-cells of mice and
      islet hyperplasia developed in a time-dependent manner. The hyperplastic beta
      cells exhibited higher rates of proliferation. However, blood glucose levels in
      fasting as well as nonfasting conditions remained normal. Furthermore, glucose
      tolerance tests demonstrated nearly normal responses, and diabetes did not
      develop in any of the animals. No islet cell tumors were observed, even among
      animals >2 years of age. Under our experimental conditions, the proliferative
      stimulus provided by cyclin D1 is not tumorigenic, does not result in diabetes,
      and does not result in hypoglycemia. Cyclin D1 may thus be considered a potential
      candidate to augment the beta-cell population ex vivo as a prelude to islet
      transplantation for diabetes.

PMID- 15734848
TI  - TAT-mediated neurogenin 3 protein transduction stimulates pancreatic endocrine
      differentiation in vitro.
AB  - Stem cell technologies hold great potential for the treatment of type 1 diabetes,
      provided that functional transplantable beta-cells can be selectively generated
      in an efficient manner. Such a process should recapitulate, at least to a certain
      extent, the embryonic development of beta-cells in vitro. However, progress at
      identifying the transcription factors involved in beta-cell development has not
      been accompanied by a parallel success at unraveling the pattern of their
      instructive extracellular signals. Here we present proof of principle of a novel
      approach to circumvent this problem, based on the use of the HIV/TAT protein
      transduction domain. Neurogenin 3 (ngn3), a factor whose expression is essential
      for pancreatic endocrine differentiation, was fused to the TAT domain.
      Administration of TAT/ngn3 to cultured pancreatic explants results in efficient
      uptake, nuclear translocation, and stimulation of downstream reporter and
      endogenous genes. Consistent with the predicted activity of the protein, e9.5 and
      e13.5 mouse pancreatic explants cultured in the presence of TAT/ngn3 show an
      increased level of endocrine differentiation compared with control samples. Our
      results raise the possibility of sequentially specifying stem/progenitor cells
      toward the beta-cell lineage, by using the appropriate sequence and combination
      of TAT-fused transcription factors.

PMID- 15734849
TI  - Functional and molecular defects of pancreatic islets in human type 2 diabetes.
AB  - To shed further light on the primary alterations of insulin secretion in type 2
      diabetes and the possible mechanisms involved, we studied several functional and
      molecular properties of islets isolated from the pancreata of 13 type 2 diabetic
      and 13 matched nondiabetic cadaveric organ donors. Glucose-stimulated insulin
      secretion from type 2 diabetic islets was significantly lower than from control
      islets, whereas arginine- and glibenclamide-stimulated insulin release was less
      markedly affected. The defects were accompanied by reduced mRNA expression of
      GLUT1 and -2 and glucokinase and by diminished glucose oxidation. In addition,
      AMP-activated protein kinase activation was reduced. Furthermore, the expression
      of insulin was decreased, and that of pancreatic duodenal homeobox-1 (PDX-1) and
      forkhead box O1 (Foxo-1) was increased. Nitrotyrosine and 8-hydroxy-2'
      deoxyguanosine concentrations, markers of oxidative stress, were significantly
      higher in type 2 diabetic than control islets, and they were correlated with the
      degree of glucose-stimulated insulin release impairment. Accordingly, 24-h
      exposure to glutathione significantly improved glucose-stimulated insulin release
      and decreased nitrotyrosine concentration, with partial recovery of insulin mRNA
      expression. These results provide direct evidence that the defects of insulin
      secretion in type 2 diabetic islets are associated with multiple islet cell
      alterations. Most importantly, the current study shows that the functional
      impairment of type 2 diabetic islets can be, at least in part, reversible. In
      this regard, it is suggested that reducing islet cell oxidative stress is a
      potential target of human type 2 diabetes therapy.

PMID- 15734850
TI  - Regulated exocytosis and kiss-and-run of synaptic-like microvesicles in INS-1 and
      primary rat beta-cells.
AB  - We have applied cell-attached capacitance measurements to investigate whether
      synaptic-like microvesicles (SLMVs) undergo regulated exocytosis in insulinoma
      and primary pancreatic beta-cells. SLMV and large dense-core vesicle (LDCV)
      exocytosis was increased 1.6- and 2.4-fold upon stimulation with 10 mmol/l
      glucose in INS-1 cells. Exocytosis of both types of vesicles was coupled to
      Ca(2+) entry through l-type channels. Thirty percent of SLMV exocytosis in INS-1
      and rat beta-cells was associated with transient capacitance increases consistent
      with kiss-and-run. Elevation of intracellular cAMP (5 micromol/l forskolin)
      increased SLMV exocytosis 1.6-fold and lengthened the duration of kiss-and-run
      events in rat beta-cells. Experiments using isolated inside-out patches of INS-1
      cells revealed that the readily releasable pool (RRP) of SLMVs preferentially
      undergoes kiss-and-run exocytosis (67%), is proportionally larger than the LDCV
      RRP, and is depleted more quickly upon Ca(2+) stimulation. We conclude that SLMVs
      undergo glucose-regulated exocytosis and are capable of high turnover. Following
      kiss-and-run exocytosis, the SLMV RRP may be reloaded with gamma-aminobutyric
      acid and undergo several cycles of exo- and endocytosis. Our observations support
      a role for beta-cell SLMVs in a synaptic-like function of rapid intra-islet
      signaling.

PMID- 15734851
TI  - Effects of sustained insulin-induced hypoglycemia on cardiovascular autonomic
      regulation in type 1 diabetes.
AB  - Effects of hypoglycemia on cardiac autonomic regulation may contribute to the
      occurrence of adverse cardiac events. This study assessed the effects of
      sustained hyperinsulinemic hypoglycemia on cardiovascular autonomic regulation in
      type 1 diabetic patients and their nondiabetic counterparts. The study consisted
      of 16 type 1 diabetic patients and 8 age-matched healthy control subjects who
      underwent euglycemic and hypoglycemic clamp procedures in a random order. Heart
      rate variability was measured from continuous electrocardiogram recordings by
      time and frequency domain methods, along with Poincare plot analysis during both
      a hyperinsulinemic-euglycemic and hypoglycemic clamp at three different glucose
      levels (4.5-5.5, 3.0-3.5, and 2.0-2.5 mmol/l). Controlled hypoglycemia resulted
      in an increase of supine heart rate in both the diabetic patients (from 72 +/- 9
      to 80 +/- 11 bpm, P < 0.01) and the control subjects (from 59 +/- 5 to 65 +/- 5
      bpm, P < 0.05) and progressive reductions of the high-frequency spectral
      component and beat-to-beat heart rate variability (SD1; P < 0.05 in the diabetic
      patients and P < 0.01 in control subjects). No significant changes in heart rate
      variability occurred during the euglycemic clamp. We conclude that hypoglycemia
      results in a reduction of cardiac vagal outflow in both diabetic and nondiabetic
      subjects. Altered autonomic regulation may contribute to the occurrence of
      cardiac events during hypoglycemia.

PMID- 15734852
TI  - Redistribution of glucose from skeletal muscle to adipose tissue during catch-up
      fat: a link between catch-up growth and later metabolic syndrome.
AB  - Catch-up growth, a risk factor for later obesity, type 2 diabetes, and
      cardiovascular diseases, is characterized by hyperinsulinemia and an accelerated
      rate for recovering fat mass, i.e., catch-up fat. To identify potential
      mechanisms in the link between hyperinsulinemia and catch-up fat during catch-up
      growth, we studied the in vivo action of insulin on glucose utilization in
      skeletal muscle and adipose tissue in a previously described rat model of weight
      recovery exhibiting catch-up fat caused by suppressed thermogenesis per se. To do
      this, we used euglycemic-hyperinsulinemic clamps associated with the labeled 2
      deoxy-glucose technique. After 1 week of isocaloric refeeding, when body fat,
      circulating free fatty acids, or intramyocellular lipids in refed animals had not
      yet exceeded those of controls, insulin-stimulated glucose utilization in refed
      animals was lower in skeletal muscles (by 20-43%) but higher in white adipose
      tissues (by two- to threefold). Furthermore, fatty acid synthase activity was
      higher in adipose tissues from refed animals than from fed controls. These
      results suggest that suppressed thermogenesis for the purpose of sparing glucose
      for catch-up fat, via the coordinated induction of skeletal muscle insulin
      resistance and adipose tissue insulin hyperresponsiveness, might be a central
      event in the link between catch-up growth, hyperinsulinemia and risks for later
      metabolic syndrome.

PMID- 15734853
TI  - Loss of the decrement in intraislet insulin plausibly explains loss of the
      glucagon response to hypoglycemia in insulin-deficient diabetes: documentation of
      the intraislet insulin hypothesis in humans.
AB  - The intraislet insulin hypothesis for the signaling of the glucagon secretory
      response to hypoglycemia states that a decrease in arterial glucose --> a
      decrease in beta-cell insulin secretion --> a decrease in tonic alpha-cell
      inhibition by insulin --> an increase in alpha-cell glucagon secretion. To test
      this hypothesis in humans, a hyperinsulinemic- euglycemic ( approximately 5.0
      mmol/l [90 mg/dl] x 2 h) and then a hypoglycemic ( approximately 3.0 mmol/l [55
      mg/dl] x 2 h) clamp was performed in 14 healthy young adults on two occasions,
      once with oral administration of the ATP-sensitive potassium channel agonist
      diazoxide to selectively suppress baseline insulin secretion and once with the
      administration of a placebo. The decrement in plasma C-peptide during the
      induction of hypoglycemia was reduced by approximately 50% in the diazoxide
      clamps (from 0.3 +/- 0.0 to 0.1 +/- 0.0 nmol/l [0.8 +/- 0.1 to 0.4 +/- 0.1
      ng/ml]) compared with the placebo clamps (from 0.4 +/- 0.0 to 0.1 +/- 0.0 nmol/l
      [1.2 +/- 0.1 to 0.4 +/- 0.1 ng/ml]) (P = 0.0015). This reduction of the decrement
      in intraislet insulin during induction of hypoglycemia caused an approximately
      50% reduction (P = 0.0010) of the increase in plasma glucagon in the diazoxide
      clamps (from 29 +/- 3 to 35 +/- 2 pmol/l [102 +/- 9 to 123 +/- 8 pg/ml]) compared
      with the placebo clamps (from 28 +/- 2 to 43 +/- 5 pmol/l [98 +/- 7 to 151 +/- 16
      pg/ml]). Baseline glucagon levels, the glucagon response to intravenous arginine,
      and the autonomic (adrenomedullary, sympathetic neural, and parasympathetic
      neural) responses to hypoglycemia were not altered by diazoxide. These data
      indicate that a decrease in intraislet insulin is a signal for the glucagon
      secretory response to hypoglycemia in healthy humans. The absence of that signal
      plausibly explains the loss of the glucagon response to falling plasma glucose
      concentrations, a key feature of the pathogenesis of iatrogenic hypoglycemia, in
      insulin-deficient (type 1 and advanced type 2) diabetes.

PMID- 15734854
TI  - Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in
      hypoadrenal women.
AB  - DHEA (dehydroepiandrosterone) replacement is not part of the current standard of
      care in hypoadrenal subjects. Animal studies have shown that DHEA administration
      prevents diabetes. To determine the physiological effect of DHEA replacement on
      insulin sensitivity in adrenal-deficient women, we performed a single-center,
      randomized, double-blind, placebo-controlled, crossover study in 28 hypoadrenal
      women (mean age 50.2 +/- 2.87 years) who received a single 50-mg dose of DHEA
      daily or placebo. After 12 weeks, insulin sensitivity was assessed using a
      hyperinsulinemic-euglycemic clamp. DHEA replacement significantly increased DHEA
      S (sulfated ester of DHEA), bioavailable testosterone, and androstenedione and
      reduced sex hormone-binding globulin levels. Fasting plasma insulin and glucagon
      were lower with DHEA (42 +/- 4.94 vs. 53 +/- 6.58 pmol/l [P = 0.005] and 178 +/-
      11.32 vs. 195.04 +/- 15 pmol/l [P = 0.02], respectively). The average amount of
      glucose needed to maintain similar blood glucose levels while infusing the same
      insulin dosages was higher during DHEA administration (358 +/- 24.7 vs. 320 +/-
      24.6 mg/min; P < 0.05), whereas endogenous glucose production was similar. DHEA
      also reduced total cholesterol (P < 0.005), triglycerides (P < 0.011), LDL
      cholesterol (P < 0.05), and HDL cholesterol (P < 0.005). In conclusion,
      replacement therapy with 50 mg of DHEA for 12 weeks significantly increased
      insulin sensitivity in hypoadrenal women, thereby suggesting that DHEA
      replacement could have a potential impact in preventing type 2 diabetes.

PMID- 15734855
TI  - Contribution of abdominal visceral obesity and insulin resistance to the
      cardiovascular risk profile of postmenopausal women.
AB  - The aim of this study was to determine the respective contribution of abdominal
      visceral adipose tissue (AT) accumulation and insulin resistance (IR) to the
      determination of a comprehensive cardiovascular metabolic risk profile in 108
      postmenopausal women not receiving hormone therapy. Insulin sensitivity (M/I) was
      determined by a hyperinsulinemic-euglycemic clamp, and visceral AT area was
      measured by computed tomography. Median values of visceral AT (133.9 cm(2)) and
      insulin sensitivity (0.010189 mg . kg(-1) . min(-1) . pmol(-1)) were used to form
      four subgroups: 1) low visceral AT-low IR (n = 35), 2) low visceral AT-high IR (n
      = 19), 3) high visceral AT-low IR (n = 19), and 4) high visceral AT-high IR (n =
      35). Women with isolated IR (low visceral AT and high IR) were characterized by
      significantly higher fasting and 2-h glycemia and higher fibrinogen,
      triglyceride, and VLDL-apolipoprotein (apo)B concentrations than women with low
      visceral AT and low IR (P < 0.05). The plasma lipid-lipoprotein profile and
      inflammatory markers were not significantly different between women with high
      visceral AT and low IR and women with low visceral AT and low IR. Women with high
      visceral AT and high IR had higher fasting and 2-h glycemia, triglyceride, and
      VLDL-apoB levels; lower apoAI and HDL(2) cholesterol levels; as well as higher C
      reactive protein and interleukin-6 concentrations than women with low visceral AT
      and low IR (P < 0.05). In addition, 15 of the 35 women (42.9%) in the high
      visceral AT and high IR group were newly diagnosed with type 2 diabetes, whereas
      no women were diagnosed with type 2 diabetes in the group of women with low
      visceral AT and low IR. These results show that although the presence of high IR
      in its isolated form is associated with some metabolic alterations, it is the
      combination of both high visceral AT and high IR that is the most detrimental for
      the metabolic health in postmenopausal women.

PMID- 15734856
TI  - Absence of heme oxygenase-1 exacerbates myocardial ischemia/reperfusion injury in
      diabetic mice.
AB  - Increased production of reactive oxygen species contributes to the etiology of
      diabetes complications. Pathophysiological stimuli that increase oxidative stress
      upregulate heme oxygenase (HO)-1, a cytoprotective heme-degrading enzyme. We
      hypothesized that HO-1 may be important in myocardial injury that is exacerbated
      by diabetes. To test this hypothesis, the left anterior descending coronary
      arteries of nondiabetic and diabetic wild-type (HO-1(+/+)) and HO-1 null (HO-1(-/
      )) mice were ligated for 1 h followed by 24 h reperfusion. The absence of HO-1
      significantly increased myocardial infarct size (36.4 +/- 2.0 vs. 21.4 +/- 1.8%
      in HO-1(+/+) mice), while cardiac-specific overexpression of HO-1 protected
      against myocardial ischemic injury in diabetic mice. Despite similar high blood
      glucose levels, diabetic HO-1(-/-) mice had fourfold higher oxidative stress and
      larger infarcts (56.0 +/- 2.8%) than diabetic HO-1(+/+) mice (30.8 +/- 6.1%).
      Moreover, hyperglycemia increased the mortality of HO-1(-/-) mice (31.3%) after
      ischemia/reperfusion injury, and 55% of diabetic HO-1(-/-) mice had mural thrombi
      in the left ventricles. The increased mortality of diabetic HO-1(-/-) mice may be
      in part due to formation of left ventricular mural thrombi. Our data demonstrate
      that the absence of HO-1 renders animals more susceptible to myocardial
      ischemia/reperfusion damage and diabetes worsens the injury.

PMID- 15734857
TI  - Impaired retinal angiogenesis in diabetes: role of advanced glycation end
      products and galectin-3.
AB  - Suppression of angiogenesis during diabetes is a recognized phenomenon but is
      less appreciated within the context of diabetic retinopathy. The current study
      has investigated regulation of retinal angiogenesis by diabetic serum and
      determined if advanced glycation end products (AGEs) could modulate this
      response, possibly via AGE-receptor interactions. A novel in vitro model of
      retinal angiogenesis was developed and the ability of diabetic sera to regulate
      this process was quantified. AGE-modified serum albumin was prepared according to
      a range of protocols, and these were also analyzed along with neutralization of
      the AGE receptors galectin-3 and RAGE. Retinal ischemia and neovascularization
      were also studied in a murine model of oxygen-induced proliferative retinopathy
      (OIR) in wild-type and galectin-3 knockout mice (gal3(-/-)) after perfusion of
      preformed AGEs. Serum from nondiabetic patients showed significantly more
      angiogenic potential than diabetic serum (P < 0.0001) and within the diabetic
      group, poor glycemic control resulted in more AGEs but less angiogenic potential
      than tight control (P < 0.01). AGE-modified albumin caused a dose-dependent
      inhibition of angiogenesis (P < 0.001), and AGE receptor neutralization
      significantly reversed the AGE-mediated suppression of angiogenesis (P < 0.01).
      AGE-treated wild-type mice showed a significant increase in inner retinal
      ischemia and a reduction in neovascularization compared with non-AGE controls (P
      < 0.001). However, ablation of galectin-3 abolished the AGE-mediated increase in
      retinal ischemia and restored the neovascular response to that seen in controls.
      The data suggest a significant suppression of angiogenesis by the retinal
      microvasculature during diabetes and implicate AGEs and AGE-receptor interactions
      in its causation.

PMID- 15734858
TI  - Adipocytokines and VLDL metabolism: independent regulatory effects of
      adiponectin, insulin resistance, and fat compartments on VLDL apolipoprotein B
      100 kinetics?
AB  - We investigated the relationship of plasma adipocytokine concentrations with VLDL
      apolipoprotein B (apoB)-100 kinetics in men. Plasma adiponectin, leptin,
      resistin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)
      concentrations were measured using enzyme immunoassays and insulin resistance by
      homeostasis model assessment (HOMA) score in 41 men with BMI of 22-35 kg/m(2).
      VLDL apoB kinetics were determined using an intravenous infusion of 1
      [(13)C]leucine, gas chromatography-mass spectrometry, and compartmental modeling.
      Visceral and subcutaneous adipose tissue mass (ATM) were determined using
      magnetic resonance imaging, and total ATM was measured by bioelectrical
      impedance. In univariate regression, plasma adiponectin and leptin concentrations
      were inversely and directly associated, respectively, with plasma triglyceride;
      HOMA score; and visceral, subcutaneous, and total ATMs. Conversely, adiponectin
      and leptin were directly and inversely correlated, respectively, with VLDL apoB
      catabolism and HDL cholesterol concentration (P < 0.05). Resistin, IL-6, and TNF
      alpha were not significantly associated with any of these variables. In
      multivariate regression, adiponectin was the most significant predictor of plasma
      VLDL apoB concentration (P = 0.001) and, together with total or subcutaneous ATM,
      was an independent predictor of VLDL apoB catabolism (P < 0.001); HOMA score was
      the most significant predictor of VLDL apoB hepatic secretion (P < 0.05). Leptin
      was not an independent predictor of VLDL apoB kinetics. In conclusion, plasma
      VLDL apoB kinetics may be differentially controlled by adiponectin and insulin
      resistance, with adiponectin regulating catabolism and insulin resistance
      regulating hepatic secretion in men. Total body fat may also independently
      determine the rate of VLDL catabolism, but leptin, resistin, IL-6, and TNF-alpha
      do not have a significant effect in regulating apoB kinetics.

PMID- 15734859
TI  - Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size
      associated with low levels of myocardial HO-1 during ischemia/reperfusion.
AB  - This study investigated the role of heme oxygenase (HO)-1 in the cardiac tissue
      injury of acute ischemia/reperfusion (I/R) in diabetic streptozotocin (STZ)
      induced hyperglycemic rats. The effects of 1) hemin, an inducer of HO expression
      and activity, and 2) zinc protoporphyrin IX (ZnPP-IX), an inhibitor of HO
      activity, have also been investigated on the tissue injury by I/R and some
      mediators released in these circumstances. STZ hyperglycemic rats had impaired
      levels of HO-1 within the cardiac tissue and increased myocardial infarct size
      (IS) following I/R, as compared with the nondiabetic rats. In these rats,
      administration of hemin 4 mg/kg 18 h before I/R increases the levels of HO-1
      within the tissue. However, the values of HO-1 assayed in these circumstances
      were significantly lower (P < 0.01) than those assayed in nondiabetic animals
      subjected to the same procedures; IS was much more extended (P < 0.01) than in
      the parent nondiabetic group. STZ hyperglycemic rats also predisposed the heart
      to produce high levels of the cytokines interleukin (IL)-1beta and CXCL8.
      Subsequent I/R further increased (P < 0.01) the cytokine production, an effect
      partly prevented by hemin treatment. This recovered the huge number of
      infiltrated polymorphonuclear (PMN) leukocytes within the cardiac tissue
      associated with the STZ hyperglycemic state and I/R damage.

PMID- 15734860
TI  - Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome
      proliferator-activated receptor-gamma, transforming growth factor-beta1, and a
      Smad2-dependent mechanism.
AB  - Thiazolidinediones, such as pioglitazone, seem to exert direct
      antiatherosclerotic and antirestenotic effects on type 2 diabetes, in part due to
      an induction of vascular smooth muscle cell (VSMC) apoptosis. We aimed to study
      the role of transforming growth factor (TGF)-beta in rat aortic VSMC.
      Pioglitazone at 100 micromol/l increased apoptosis without affecting DNA
      synthesis, and this effect was reversed by an anti-TGF-beta1 antibody.
      Extracellular TGF-beta1 levels were rapidly increased after treatment with
      pioglitazone in a peroxisome proliferator-activated receptor (PPAR)-gamma
      dependent mechanism because this secretion was blocked by the PPAR-gamma
      inhibitor GW9662. Pioglitazone subsequently increased the nuclear recruitment of
      phospho-Smad2, without any effect on protein expression. According to our
      results, we propose that the apoptotic effect of pioglitazone on VSMC depends on
      the following sequence: PPAR-gamma activation, TGF-beta1 release, and selective
      phospho-Smad2 nuclear recruitment. Management of Smad signaling on VSMC might
      provide future clinical benefits in vascular diseases.

PMID- 15734861
TI  - Requirement of aldose reductase for the hyperglycemic activation of protein
      kinase C and formation of diacylglycerol in vascular smooth muscle cells.
AB  - Activation of protein kinase C (PKC) has been linked to the development of
      secondary diabetes complications. However, the underlying molecular mechanisms
      remain unclear. We examined the contribution of aldose reductase, which catalyzes
      the first, and the rate-limiting, step of the polyol pathway of glucose
      metabolism, to PKC activation in vascular smooth muscle cells (VSMCs) isolated
      from rat aorta and exposed to high glucose in culture. Exposure of VSMCs to high
      glucose (25 mmol/l), but not iso-osmotic mannitol, led to an increase in total
      membrane-associated PKC activity, which was prevented by the aldose reductase
      inhibitors tolrestat or sorbinil or by the ablation of aldose reductase by small
      interfering RNA (siRNA). The VSMCs were found to express low levels of sorbitol
      dehydrogenase, and treatment with the sorbitol dehydrogenase inhibitor CP-166572
      did not prevent high-glucose-induced PKC activation. Stimulation with high
      glucose caused membrane translocation of conventional (alpha, beta1, beta2, and
      gamma) and novel (delta and epsilon) isoforms of PKC. Inhibition of aldose
      reductase prevented membrane translocation of PKC-beta2 and -delta and delayed
      the activation of PKC-beta1 and -epsilon, whereas membrane translocation of PKC
      alpha and -gamma was not affected. Treatment with tolrestat prevented
      phosphorylation of PKC-beta2 and -delta. High glucose increased the formation of
      diacylglycerol (DAG) and enhanced phosphorylation of phospholipase C-gamma1 (PLC
      gamma1). Inhibition of aldose reductase prevented high glucose-induced DAG
      formation and phosphorylation of PLC-gamma1 and PLC-beta2 and -delta. Inhibition
      of phospholipid hydrolysis by D609, but not by the synthetic alkyl-1
      lysophospholipid 1-O-octadecyl-2-O-methyl-rac-glycerophosphocholine, or
      edelfosine, prevented DAG formation. Treatment with sorbinil decreased the levels
      of reactive oxygen species in high-glucose-stimulated VSMCs. Hence, inhibition of
      aldose reductase, independent of sorbitol dehydrogenase, appears to be effective
      in diminishing oxidative stress and hyperglycemic changes in signaling events
      upstream to the activation of multiple PKC isoforms and PLC-gamma1 and may
      represent a useful approach for preventing the development of secondary vascular
      complications of diabetes.

PMID- 15734862
TI  - Experimental diabetic neuropathy with spontaneous recovery: is there irreparable
      damage?
AB  - Progressive diabetic neuropathy has hitherto been irreversible in humans. New
      approaches raise the question of whether islet cell reconstitution rendering
      euglycemia can reverse specific features of neuropathy. We evaluated
      physiological and structural features of experimental neuropathy in a long-term
      murine model of diabetes induced by streptozotocin. By serendipity, a subset of
      these diabetic mice spontaneously regained islet function and attained near
      euglycemia. Our hypotheses were that this model might better reflect axon loss
      observed in human disease and that spontaneous recovery from diabetes might
      identify the features of neuropathy that are reversible. In this model,
      experimental neuropathy closely modeled that in humans in most critical aspects:
      declines in motor conduction velocities, attenuation of compound muscle (M waves)
      and nerve action potentials, axon atrophy, myelin thinning, loss of epidermal
      axons, and loss of sweat gland innervation. Overt sensory neuron loss in dorsal
      root ganglia was a feature of this model. In mice with recovery, there was robust
      electrophysiological improvement, less myelin thinning, and remarkable epidermal
      and sweat gland reinnervation. There was, however, no recovery of populations of
      lost sensory neurons. Our findings identify a robust model of human diabetic
      neuropathy and indicate that overt, irretrievable loss of sensory neurons is one
      of its features, despite collateral reinnervation of target organs. Sensory
      neurons deserve unique protective strategies irrespective of islet cell
      reconstitution.

PMID- 15734864
TI  - Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin
      induced diabetic neuropathy in rats.
AB  - Peripheral neuropathy is common and ultimately accounts for significant morbidity
      in diabetes. Recently, several neurotrophic factors have been used to prevent
      progression of diabetic neuropathy. In this study, we gave repeated intramuscular
      injections of the human hepatocyte growth factor (HGF) gene percutaneously, using
      liposomes containing the hemagglutinating virus of Japan (HVJ), to examine
      therapeutic efficacy of nonviral gene transfer of HGF for experimental diabetic
      sensorimotor neuropathy in rats. Experimental diabetes induced by intraperitoneal
      injection of streptozotocin resulted in a marked tactile allodynia (but not in a
      thermal hyperalgesia), in a reduction of both the conduction velocity and the
      amplitude, and in a decreased laser Doppler flux of the nerve and the muscle at 6
      weeks after the induction. All these changes were significantly reversed by
      repeated gene transfer of HGF. Furthermore, we analyzed the density of
      endoneurial capillaries and morphometrical changes of the nerve. The density of
      endoneurial capillaries, disclosing marked reduction in diabetic rats, was also
      reversed significantly by repeated gene transfer of HGF; however, no considerable
      differences were observed morphometrically in either myelinated or unmyelinated
      axons. These results suggest that nonviral HVJ liposome-mediated gene transfer of
      human HGF has potential for the safe effective treatment of diabetic sensorimotor
      neuropathy.

PMID- 15734863
TI  - N-acetyl-seryl-aspartyl-lysyl-proline prevents renal insufficiency and mesangial
      matrix expansion in diabetic db/db mice.
AB  - We have previously reported that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP),
      which is a tetrapeptide hydrolyzed by ACE, inhibits the transforming growth
      factor-beta (TGF-beta)-induced expression of extracellular matrix proteins via
      inhibition of the Smad signaling in human mesangial cells. To test in vivo the
      antifibrotic efficacy of Ac-SDKP, we examined whether long-term Ac-SDKP treatment
      can prevent renal insufficiency and glomerulosclerosis in diabetic db/db mice.
      Diabetic db/db mice or nondiabetic db/m mice were treated with Ac-SDKP for 8
      weeks using osmotic minipumps. The treatment with Ac-SDKP increased plasma Ac
      SDKP concentrations by approximately threefold in both groups but did not affect
      the blood glucose levels. Histologically, the increased glomerular surface area,
      mesangial matrix expansion, and overproduction of extracellular matrix proteins
      in db/db mice were significantly inhibited by Ac-SDKP. Furthermore, Ac-SDKP
      treatment normalized the increased plasma creatinine value in db/db mice, whereas
      the albuminuria in Ac-SDKP-treated db/db mice was somewhat decreased as compared
      with nontreated db/db mice, although the difference was not statistically
      significant. In addition, the nuclear translocation of Smad3 was inhibited by Ac
      SDKP. These results demonstrate that long-term Ac-SDKP treatment ameliorates
      renal insufficiency and glomerulosclerosis in db/db mice via inhibition of TGF
      beta/Smad pathway, suggesting that Ac-SDKP could be useful in the treatment of
      diabetic nephropathy.

PMID- 15734865
TI  - Topical pretreatment of diabetic rats with all-trans retinoic acid improves
      healing of subsequently induced abrasion wounds.
AB  - In the current study, rats were made diabetic with streptozotocin (STZ) and
      maintained for 8 weeks, during which time they were treated topically on
      alternative days with a solution of 0.1% all-trans retinoic acid in a vehicle of
      70:30% ethanol/propylene glycol. STZ-induced diabetic rats treated with vehicle
      served as controls. Additional nondiabetic rats were treated with all-trans
      retinoic acid or vehicle in parallel. At the end of the 8-week period, rats from
      all four treatment groups were subjected to abrasion wound formation. Wounds
      healed more rapidly in vehicle-treated nondiabetic skin than in vehicle-treated
      diabetic skin (96% of the wound surface area closed in nondiabetic rats within 6
      days vs. 41% closed in diabetic rats). Wounds in all-trans retinoic acid-treated
      diabetic skin healed more rapidly than wounds in vehicle-treated diabetic skin
      (85% of the wound surface area closed in all-trans retinoic acid-treated diabetic
      rats vs. 41% closed in vehicle-treated diabetic rats). At the histological level,
      recently healed skin from vehicle-treated diabetic rats was shown to contain a
      thin, wispy provisional matrix in which many of the embedded cells were rounded
      and some were pycnotic. In contrast, a much denser provisional matrix with large
      numbers of embedded spindle-shaped cells was observed in healed wounds from
      diabetic skin that had been pretreated with all-trans retinoic acid. The all
      trans retinoic acid-treated diabetic skin was histologically similar to vehicle
      treated (or all-trans retinoic acid-treated) skin from nondiabetic animals. In
      light of these findings, we suggest that prophylactic use of retinoid-containing
      preparations might be useful in preventing the development of nonhealing skin
      ulcers resultant from minor traumas in at-risk skin.

PMID- 15734866
TI  - Metabolic dysregulation with atypical antipsychotics occurs in the absence of
      underlying disease: a placebo-controlled study of olanzapine and risperidone in
      dogs.
AB  - Atypical antipsychotics have been linked to weight gain, hyperglycemia, and
      diabetes. We examined the effects of atypical antipsychotics olanzapine (OLZ) and
      risperidone (RIS) versus placebo on adiposity, insulin sensitivity (S(I)), and
      pancreatic beta-cell compensation. Dogs were fed ad libitum and given OLZ (15
      mg/day; n = 10), RIS (5 mg/day; n = 10), or gelatin capsules (n = 6) for 4-6
      weeks. OLZ resulted in substantial increases in adiposity: increased total body
      fat (+91 +/- 20%; P = 0.000001) reflecting marked increases in subcutaneous (+106
      +/- 24%; P = 0.0001) and visceral (+84 +/- 22%; P = 0.000001) adipose stores.
      Changes in adiposity with RIS were not different from that observed in the
      placebo group (P > 0.33). Only OLZ resulted in marked hepatic insulin resistance
      (hepatic S(I) [pre- versus postdrug]: 6.05 +/- 0.98 vs. 1.53 +/- 0.93 dl . min(
      1) . kg(-1)/[microU/ml], respectively; P = 0.009). beta-Cell sensitivity failed
      to upregulate during OLZ (pre-drug: 1.24 +/- 0.15, post-drug: 1.07 +/- 0.25
      microU . ml(-1)/[mg/dl]; P = 0.6). OLZ-induced beta-cell dysfunction was further
      demonstrated when beta-cell compensation was compared with a group of animals
      with adiposity and insulin resistance induced by moderate fat feeding alone (+8%
      of calories from fat; n = 6). These results may explain the diabetogenic effects
      of atypical antipsychotics and suggest that beta-cell compensation is under
      neural control.

PMID- 15734867
TI  - Increased in vivo regeneration of cortisol in adipose tissue in human obesity and
      effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor
      carbenoxolone.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11HSD1) regenerates cortisol from
      cortisone within adipose tissue and liver. 11HSD1 inhibitors may enhance insulin
      sensitivity in type 2 diabetes and be most efficacious in obesity when 11HSD1 is
      increased in subcutaneous adipose biopsies. We examined the regeneration of
      cortisol in vivo in obesity, and the effects of the 11HSD1 inhibitor
      carbenoxolone. We compared six lean and six obese men and performed a randomized,
      placebo-controlled crossover study of carbenoxolone in obese men. The obese men
      had no difference in their whole-body rate of regenerating cortisol (measured
      with 9,11,12,12-[(2)H(4)]cortisol tracer), but had more rapid conversion of
      [(3)H]cortisone to [(3)H]cortisol in abdominal subcutaneous adipose tissue
      (measured with microdialysis). During insulin infusion, adipose 11HSD1 activity
      fell markedly in lean but not in obese men. Carbenoxolone inhibited whole-body
      cortisol regeneration, but did not significantly inhibit adipose 11HSD1 and had
      no effects on insulin sensitivity (measured by [(2)H(2)]glucose infusion with or
      without hyperinsulinemia). Thus, in vivo cortisol generation is increased
      selectively within adipose tissue in obesity, perhaps reflecting resistance to
      insulin-mediated downregulation of 11HSD1. However, obese men are less
      susceptible than lean men to the insulin-sensitizing effects of carbenoxolone. To
      be useful in obese patients, 11HSD1 inhibitors will need to inhibit the enzyme
      more effectively in adipose tissue.

PMID- 15734868
TI  - Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue
      of diabetic patients.
AB  - Thiazolidinediones (TZDs) are a new class of insulin-sensitizing drugs. To
      explore how and in which tissues they improve insulin action, we obtained fat and
      muscle biopsies from eight patients with type 2 diabetes before and 2 months
      after treatment with rosiglitazone (n = 5) or troglitazone (n = 3). TZD treatment
      was associated with a coordinated upregulation in the expression of genes and
      synthesis of proteins involved in fatty acid uptake, binding, beta-oxidation and
      electron transport, and oxidative phosphorylation in subcutaneous fat but not in
      skeletal muscle. These changes were accompanied by a 13% increase in total body
      fat oxidation, a 20% decrease in plasma free fatty acid levels, and a 46%
      increase in insulin-stimulated glucose uptake. We conclude that TZDs induced a
      coordinated stimulation of fatty acid uptake, oxidation, and oxidative
      phosphorylation in fat of diabetic patients and thus may have corrected, at least
      partially, a recently recognized defect in patients with type 2 diabetes
      consisting of reduced expression of genes related to oxidative metabolism and
      mitochondrial function.

PMID- 15734870
TI  - The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276)
      of the adiponectin gene predict the conversion from impaired glucose tolerance to
      type 2 diabetes: the STOP-NIDDM trial.
AB  - Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and
      antiatherogenic properties. Therefore, the adiponectin gene is a promising
      candidate gene for type 2 diabetes. We investigated the single nucleotide
      polymorphisms (SNPs) +45T/G and +276G/T of the adiponectin gene as predictors for
      the conversion from impaired glucose tolerance to type 2 diabetes in the STOP
      NIDDM trial, which aimed to investigate the effect of acarbose compared with
      placebo on the prevention of type 2 diabetes. Compared with the TT genotype, the
      G-allele of SNP +45 was associated with a 1.8-fold risk for type 2 diabetes (95%
      CI 1.12-3.00, P = 0.015) in the placebo group. Subjects treated with placebo and
      simultaneously having the G-allele of SNP +45 and the T-allele of SNP +276 (the
      risk genotype combination) had a 4.5-fold (1.78-11.3, P = 0.001) higher risk of
      developing type 2 diabetes compared with subjects carrying neither of these
      alleles. Women carrying the risk genotype combination had an especially high risk
      of conversion to diabetes (odds ratio 22.2, 95% CI 2.7-183.3, P = 0.004). In
      conclusion, the G-allele of SNP +45 is a predictor for the conversion to type 2
      diabetes. Furthermore, the combined effect of SNP +45 and SNP +276 on the
      development of type 2 diabetes was stronger than that of each SNP alone.

PMID- 15734869
TI  - Association testing of variants in the hepatocyte nuclear factor 4alpha gene with
      risk of type 2 diabetes in 7,883 people.
AB  - Two recent publications reported association of common polymorphisms in the P2
      promoter of hepatocyte nuclear factor 4alpha (HNF4alpha) (the MODY1 gene) with
      risk for type 2 diabetes. We attempted to reproduce this putative association by
      genotyping 11 single nucleotide polymorphism (SNPs) spanning the HNF4alpha coding
      region and the P2 promoter in >3,400 patients and control subjects from Sweden,
      Finland, and Canada. One SNP that was consistently associated in the two previous
      reports (rs1884613, in the P2 promoter region) also trended in the same direction
      in our sample, albeit with a lower estimated odds ratio (OR) of 1.11 (P = 0.05,
      one-tailed). We genotyped this SNP (rs1884613) in an additional 4,400 subjects
      from North America and Poland. In this sample, the association was not confirmed
      and trended in the opposite direction (OR 0.88). Meta-analysis of our combined
      sample of 7,883 people (three times larger than the two initial reports combined)
      yielded an OR of 0.97 (P = 0.27). Finally, we provide an updated analysis of
      haplotype structure in the region to guide any further investigation of common
      variation in HNF4alpha. Although our combined results fail to replicate the
      previously reported association of common variants in HNF4alpha with risk for
      type 2 diabetes, we cannot exclude an effect smaller than that originally
      proposed, heterogeneity among samples, variation in as-yet-unmeasured genotypic
      or environmental modifiers, or true association secondary to linkage
      disequilibrium (LD) with as-yet-undiscovered variant(s) in the region.

PMID- 15734871
TI  - Retrovirus-like long-terminal repeat DQ-LTR13 and genetic susceptibility to type
      1 diabetes and autoimmune Addison's disease.
AB  - Controversial data are available on the association between the retrovirus-like
      long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes
      and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic
      patients, 166 autoimmune Addison's disease (AAD) patients, 1,054 healthy
      subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more
      frequent among patients than healthy subjects (P(c) < 0.0006), and a preferential
      transmission of DQB1*0302-LTR13(+) from parents to type 1 diabetic offspring was
      observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*0302 but not
      DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to
      3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169
      DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy
      subjects (P(c) < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive
      healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele
      (P(c) = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13
      is not independently associated with type 1 diabetes and AAD after correction for
      DQB1*0302 and DRB1*0403. Conversely, DQB1*0201, DQB1*0302, DRB1*0401, and
      DRB1*0403 were all significantly associated with disease risk also after
      correction for DQ-LTR13. We provide conclusive evidence that the genetic
      association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD
      with DQB1*0302 and DRB1*0403.

PMID- 15734872
TI  - Genetic association between a lymphoid tyrosine phosphatase (PTPN22) and type 1
      diabetes.
AB  - The lymphoid-specific phosphatase (LYP) encoded by PTPN22 is involved in
      preventing spontaneous T-cell activation by dephosphorylating and inactivating T
      cell receptor-associated Csk kinase. We have genotyped 396 type 1 diabetic
      patients and 1,178 control subjects of Caucasian descent from north central
      Florida and report a strong association between type 1 diabetes and a
      polymorphism (R620W) in the PTPN22 gene. The homozygous genotype for the T allele
      encoding the 620W residue is associated with an increased risk for developing
      type 1 diabetes (odds ratio [OR] = 3.4, P < 0.008), and the heterozygous genotype
      C/T had an OR of 1.7 (P = 6 x 10(-6)). The C/C homozygous genotype is protective
      against type 1 diabetes (OR = 0.5, P = 6 x 10(-6)). Furthermore, transmission
      disequilibrium analysis of 410 affected sibpair and simplex families of Caucasian
      descent indicated that the type 1 diabetes-associated T allele is transmitted
      more often (57.2%) than randomly expected (P < 0.003). Together with previous
      reports of the association between PTPN22 and type 1 diabetes, as well as
      rheumatoid arthritis and systemic lupus erythematosus, these results provide
      compelling evidence that LYP is a critical player in multiple autoimmune
      disorders.

PMID- 15734873
TI  - Genome-wide linkage scans for fasting glucose, insulin, and insulin resistance in
      the National Heart, Lung, and Blood Institute Family Blood Pressure Program:
      evidence of linkages to chromosome 7q36 and 19q13 from meta-analysis.
AB  - Genome-wide linkage analyses were performed using a multipoint variance
      components method in eight study groups from four multicenter networks (whites
      and blacks in GenNet; whites, blacks, and Mexican Americans in GENOA; whites and
      blacks in HyperGEN; and Asians in SAPPHIRe) that comprise the National Heart,
      Lung, and Blood Institute Family Blood Pressure Program (FBPP), in order to
      identify quantitative trait loci (QTLs) influencing fasting glucose, insulin, and
      homeostasis model assessment of insulin resistance (HOMA-IR). These study
      populations were enriched with subjects who had elevated blood pressure.
      Participants fasting <8 h, those with a history of type 2 diabetes, or those on
      antidiabetic medications were excluded from the current investigation. These
      three phenotypes were suitably transformed to approximate normal distributions.
      Each phenotype was adjusted for the effects of age, BMI, and field center
      separately by sex within each of the eight network ethnicity groups before
      genetic analysis. A total of 8,664 subjects comprising 5,923 sibpairs from 4,043
      families with 365 markers were available for conducting a meta-analysis using a
      modified Fisher's method of combining the P values from each of the eight scans.
      Evidence of linkages was found on chromosome 7q36 at 163 cM, with a logarithm of
      odds (LOD) score of 3.21 for HOMA-IR, and on chromosome 19q13 at 88 cM, with a
      LOD score of 3.33 for fasting glucose. We also found suggestive linkages (LOD
      score >/=2.2) on chromosome 7q36 at 163 cM, with LOD scores of 2.31 for fasting
      glucose and 2.26 for fasting insulin (versus the LOD score of 3.21 for HOMA-IR at
      this locus). In conclusion, QTLs were identified on chromosomes 7q36 and 19q13
      for fasting glucose, insulin, and insulin resistance in large and multiple
      ethnicity populations in the FBPP with good replications across several other
      independent studies for relevant traits. Follow-up dense mapping and association
      studies are warranted.

PMID- 15734874
TI  - Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A
      arterioles in mouse cremaster muscle.
AB  - Hypercholesterolemia and atherosclerosis have been associated with changes in the
      microvasculature, in particular with endothelial dysfunction. In the present
      study, the impact of atherogenic conditions on arteriolar vasomotor control was
      determined. Arteriolar [second-order (2A) and third-order (3A) arterioles;
      diameter range: 9-37 microm] responses during reactive hyperemia (RH) were
      determined in cremaster muscle of anesthetized mice. C57Bl/6 mice on normal
      rodent chow were used as controls and high-fat/high-cholesterol (HFC)-fed C57Bl/6
      and ApoE3-Leiden mice as hypercholesterolemic mice. The HFC diet resulted in time
      dependent increases in plasma cholesterol and triglyceride concentrations (P <
      0.001), which were more pronounced in ApoE3-Leiden mice (P < 0.001). In control
      mice, inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine (L
      NNA) reduced baseline diameter from 17.9 +/- 1.2 to 15.9 +/- 1.3 microm (P <
      0.05) and decreased the duration of RH [time to 50% (t50) of recovery: 23.3 +/-
      3.6 vs. 12.5 +/- 1.3 s (P = 0.003)]. t50 was longer in 2A versus 3A arterioles
      (33 +/- 3 vs. 18 +/- 2 s, P < 0.001) and increased with wall shear rate at the
      beginning of RH in 2A arterioles only. Compared with control mice, RH duration
      was reduced in 2A arterioles of HFC mice (t50: 11 +/- 2 s, P < 0.001 vs. control)
      but not affected in 3A vessels. L-NNA did not affect baseline diameter in HFC
      mice and reduced t50 only in "slow" responders (t50 > or = 10 s). It is concluded
      that hypercholesterolemia results in an impairment of NO-mediated vasomotor
      control in 2A but not 3A arterioles during dynamic changes of perfusion like RH.
      2A arterioles likely therefore represent the functional locus of endothelial
      dysfunction during atherogenic conditions.

PMID- 15734875
TI  - Chronic beta-agonist administration affects cardiac function of adult but not old
      rats, independent of beta-adrenoceptor density.
AB  - Although beta-adrenoceptor agonists have clinical merit for attenuating the age
      related loss of skeletal muscle mass and strength (sarcopenia), potential cardiac
      related side effects may limit their clinical application. The aim of this study
      was to determine whether chronic beta-agonist administration impairs cardiac
      function in adult or aged rats. Adult (16 mo) and aged (28 mo) Fischer 344 rats
      were treated with fenoterol (1.4 mg.kg(-1).day(-1) ip) or vehicle for 4 wk. Heart
      function was assessed in vitro before analyses of cardiac structure and beta
      adrenoceptor density. Heart mass increased 17% and 25% in fenoterol-treated adult
      and aged rats, respectively. The increased heart mass in aged, but not adult,
      rats was associated with a relative increase in collagen content. Cardiac
      hypertrophy in adult rats was associated with an increase in left ventricular
      developed pressure, a marked reduction in cardiac output, and a reduction in
      coronary flow per unit heart mass. In contrast, negligible differences in
      ventricular function were observed in fenoterol-treated aged rats. The
      differential effect on contractile function was not associated with age-related
      differences in beta-adrenoceptor density but, rather, an age-related increase in
      downregulation after treatment. Our results show that chronic beta-agonist
      treatment impairs cardiac function to a greater extent in adult than in aged
      rats. These results provide important information regarding the potential effects
      of chronic beta-agonist use on cardiac function and the future development of
      safe and effective treatments for sarcopenia.

PMID- 15734876
TI  - Mechanism of salutary effects of estradiol on organ function after trauma
      hemorrhage: upregulation of heme oxygenase.
AB  - A growing body of evidence indicates that heme degradation products may
      counteract the deleterious consequences of hypoxia and/or ischemia-reperfusion
      injury. Because heme oxygenase (HO)-1 induction after adverse circulatory
      conditions is known to be protective, and because females in the proestrus cycle
      (with high estrogen) have better hepatic function and less hepatic damage than
      males after trauma-hemorrhage, we hypothesized that estrogen administration in
      males after trauma-hemorrhage will upregulate HO activity and protect the organs
      against dysfunction and injury. To test this hypothesis, male Sprague-Dawley rats
      underwent 5-cm laparotomy and hemorrhagic shock (35-40 mmHg for 93 +/- 2 min),
      followed by resuscitation with four times the shed blood volume in the form of
      Ringer lactate. 17beta-Estradiol and/or the specific HO enzyme inhibitor chromium
      mesoporphyrin (CrMP) were administered at the end of resuscitation, and the
      animals were killed 24 h thereafter. Trauma-hemorrhage reduced cardiac output,
      myocardial contractility, and serum albumin levels. Portal pressure and serum
      alanine aminotransferase levels were markedly increased under those conditions.
      These parameters were significantly improved in the 17beta-estradiol-treated
      rats. Estradiol treatment also induced increased HO-1 mRNA expression, HO-1
      protein levels, and HO enzymatic activity in cardiac and hepatic tissue compared
      with vehicle-treated trauma-hemorrhage rats. Administration of the HO inhibitor
      CrMP prevented the estradiol-induced attenuation of shock-induced organ
      dysfunction and damage. Thus the salutary effects of estradiol administration on
      organ function after trauma-hemorrhage are mediated in part via upregulation of
      HO-1 expression and activity.

PMID- 15734877
TI  - Nitric oxide, VEGF, and VEGFR-2: interactions in activity-induced angiogenesis in
      rat skeletal muscle.
AB  - Vascular endothelial growth factor (VEGF) is considered to be important in
      promotion of capillary growth in skeletal muscles exposed to increased activity.
      We studied its interactions with nitric oxide (NO) by examining the expression of
      endothelial NO synthase (NOS), VEGF, and VEGF receptor-2 (VEGFR-2) proteins in
      relation to capillary growth in rat extensor digitorum longus muscles
      electrically stimulated for 2, 4, or 7 days with and without NOS inhibition by
      N(omega)-nitro-L-arginine (L-NNA, 3 mg/day). Stimulation increased all proteins
      from 2 days onward, concomitantly with capillary proliferation (labeling for
      proliferating cell nuclear antigen). Capillary-to-fiber ratio was elevated by 25%
      after 7 days. Concurrent oral administration of L-NNA did not affect the increase
      in endothelial NOS but depressed its activity, as shown by increased blood
      pressure and decreased arteriolar diameters in 2-day-stimulated muscles. NOS
      inhibition eliminated the increased expression of VEGFR-2 and VEGF proteins in
      muscles stimulated for 2 and 4 days but not for 7 days. However, it depressed
      capillary proliferation and the increase in C/F at all time points. We conclude
      that, in stimulated muscles, NO, generated by activation of neuronal NOS by
      muscle activity or endothelial NOS by increased blood flow and capillary shear
      stress, may increase capillary proliferation in the early stages of stimulation
      through upregulation of VEGFR-2 and VEGF. With longer stimulation, capillary
      growth appears to require NO, and high levels of VEGF and VEGFR-2 may be
      contributing to maintenance of the increased capillary bed.

PMID- 15734878
TI  - Increased contractility of cardiomyocytes from copper-deficient rats is
      associated with upregulation of cardiac IGF-I receptor.
AB  - Hearts from severely Cu-deficient rats show a variety of pathological defects,
      including hypertrophy and, in intact hearts, depression of contractile function.
      Paradoxically, isolated cardiomyocytes from these rats exhibit enhanced
      contractile properties. Because hypertrophy and enhanced contractility observed
      with other pathologies are associated with elevation of insulin-like growth
      factor-I (IGF)-I, this mechanism was examined for the case of dietary Cu
      deficiency. Male, weanling Sprague-Dawley rats were provided diets that were
      deficient (approximately 0.5 mg Cu/kg diet) or adequate (approximately 6 mg Cu/kg
      diet) in Cu for 5 wk. IGF-I was measured in serum and hearts by an ELISA method,
      cardiac IGF-I and IGF-II receptors and IGFBP-3 were measured by Western blotting
      analysis, and mRNAs for cardiac IGF-I and IGF-II were measured by RT-PCR.
      Contractility of isolated cardiomyocytes was assessed by a video-based edge
      detection system. Cu deficiency depressed serum and heart IGF-I and heart IGFBP-3
      protein levels and increased cardiac IGF-I receptor protein. Cardiac IGF-II
      protein and mRNA for cardiac IGF-I and IGF-II were unaffected by Cu deficiency. A
      Cu deficiency-induced increase in cardiomyocyte contractility, as indicated by
      increases in maximal velocities of shortening (-dL/dt) and relengthening (+dL/dt)
      and decrease in time to peak shortening (TPS), was confirmed. These changes were
      largely inhibited by use of H-1356, an IGF-I receptor blocker. We conclude that
      enhanced sensitivity to IGF-I, as indicated by an increase in IGF-I receptor
      protein, accounts for the increased contractility of Cu-deficient cardiomyocytes
      and may presage cardiac failure.

PMID- 15734880
TI  - Radionuclide plethysmography for noninvasive evaluation of peripheral arterial
      blood flow.
AB  - We validated a noninvasive radionuclide plethysmography technique to evaluate
      peripheral arterial blood flow during reactive hyperemia. This method, based on
      the measurement of blood volume variations during repetitive venous occlusions,
      was compared with strain-gauge venous impedance plethysmography. The technique
      uses 99mTc-labeled autologous red blood cells scintigraphy to determine the rate
      of change of forearm scintigraphic counts during venous occlusion. Thirteen
      subjects were simultaneously evaluated with radionuclide and impedance
      plethysmography. Six baseline flow measurements were performed to evaluate the
      reproducibility of each method. Twenty-seven serial measurements were then made
      to evaluate flow variation during forearm reactive hyperemia. After 30 min of
      recovery, resting forearm blood flows were again evaluated. Impedance and
      radionuclide methods showed excellent reproducibility with intraclass correlation
      coefficients of 0.96 and 0.93, respectively. There was also good correlation of
      flows between both methods during reactive hyperemia (r = 0.87). Resting flows at
      30 min after reactive hyperemia were slightly lower than at baseline with both
      methods. We conclude that radionuclide plethysmography could be used for the
      noninvasive evaluation of forearm blood flow and its dynamic variations during
      reactive hyperemia.

PMID- 15734879
TI  - Sodium balance, arterial pressure, and the role of the subfornical organ during
      chronic changes in dietary salt.
AB  - The subfornical organ (SFO), one of the brain circumventricular organs, is known
      to mediate some of the central effects of angiotensin II related to sodium and
      water homeostasis. Because angiotensin II levels are altered with changes in
      chronic dietary salt intake, we reasoned that the actions of angiotensin II at
      the SFO might be involved in the regulation of arterial pressure during long-term
      alterations in dietary salt. The present study was designed to test the
      hypothesis that long-term control of arterial pressure during chronic changes in
      dietary salt intake requires an intact SFO. Male Sprague-Dawley rats were
      randomly selected for electrolytic lesion (SFOx, n = 8) or sham (n = 9) operation
      of the SFO. After a 1-wk recovery period, rats were instrumented with radio
      telemetric blood pressure transducers for continuous 24-h measurement of mean
      arterial pressure (MAP) and heart rate (HR) and then were placed individually in
      metabolic cages. After another 1 wk of recovery, the rats were subjected to a 49
      day protocol as follows: 1) a 7-day control period (1.0% NaCl diet), 2) 14 days
      of high-salt (4.0% NaCl) diet, 3) 7 days of normal-salt (1.0% NaCl) diet, 4) 14
      days of low-salt (0.1% NaCl) diet, and 5) 7 days of recovery (1.0% NaCl diet).
      There were no significant differences in MAP or HR between SFOx and sham-operated
      rats throughout the protocol. These results do not support the hypothesis that
      the SFO is necessary for regulation of arterial pressure during chronic changes
      in dietary salt. However, SFOx rats demonstrated significantly less cumulative
      sodium balance than sham-operated rats on days 2-6 of the high-salt diet period.
      These data suggest that the SFO is important in the regulation of sodium
      homeostasis during chronic changes in salt intake.

PMID- 15734882
TI  - Variants of the tissue-sensor array window chamber.
AB  - Sensors are being developed that can be implanted in tissues for continuous
      monitoring of oxygen, glucose, and other metabolites. However, there have been
      difficulties in inferring metabolite concentrations in blood from the signals of
      tissue sensors due to the properties of tissues at the implant site and local
      physiological phenomena that can affect sensor responses. A multisensor array has
      been previously developed for implantation in a hamster skinfold window chamber
      preparation to study these effects. The preparation allows recording of
      concentration-dependent signals from multiple sensors while nondestructively
      visualizing the adjacent tissue and microvascular function. Variants of the
      tissue-sensor array window chamber described here have respective advantages over
      the original chamber design, including improved tissue visualization and reduced
      surgical intervention, and allow exposure of the sensor to different tissues.
      Results indicate that mass transfer within tissues is heterogeneous, and sensor
      signals are affected by variable perfusion of local microvasculature in addition
      to vascular metabolite concentration. These observations suggest new strategies
      for sensor design and operation. Window chamber variants are important tools for
      validation of implanted sensors.

PMID- 15734881
TI  - Cellular mechanisms underlying cutaneous pressure-induced vasodilation: in vivo
      involvement of potassium channels.
AB  - In the skin of humans and rodents, local pressure induces localized cutaneous
      vasodilation, which may be protective against pressure-induced microvascular
      dysfunction and lesion formation. Once activated by the local pressure
      application, capsaicin-sensitive nerve fibers release neuropeptides that act on
      the endothelium to synthesize and release nitric oxide (NO) and prostaglandins,
      leading to the development of the cutaneous pressure-induced vasodilation (PIV).
      The present study was undertaken to test in vivo the hypothesis that PIV is
      mediated or modulated by differential activation of K+ channels in anesthetized
      rats using pharmacological methods. Local pressure was applied at 11.1 Pa/s.
      Endothelium-independent and -dependent vasodilation were tested using
      iontophoretic delivery of sodium nitroprusside (SNP) and acetylcholine (ACh),
      respectively, and was correlated with PIV response. PIV was reduced after
      systemic administration of tetraethylammonium (a nonspecific K+ channel blocker),
      iberiotoxin [a specific large-conductance Ca2+-activated K+ (BKCa) channel
      blocker], and glibenclamide [a specific ATP-sensitive K+ (KATP) channel blocker],
      whereas PIV was unchanged by apamin (a specific small-conductance Ca2+-activated
      K+ channel blocker) and 4-aminopyridine (a specific voltage-sensitive K+ channel
      blocker). The responses to SNP and ACh were reduced by iberiotoxin but were
      unchanged by glibenclamide. We conclude that the cellular mechanism of PIV in
      skin involves BKCa and KATP channels. We suggest that the opening of BKCa and
      KATP channels contributes to the hyperpolarization of vascular smooth muscle
      cells to produce PIV development mainly via the NO and prostaglandin pathways,
      respectively.

PMID- 15734883
TI  - Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin
      resistance and the metabolic syndrome.
AB  - Type 2 diabetes mellitus (DM) and the metabolic syndrome, both characterized by
      insulin resistance, are associated with an accelerated form of atherosclerotic
      vascular disease and poor outcomes following vascular interventions. These
      vascular effects are thought to stem from a heightened inflammatory environment
      and reduced bioavailability of nitric oxide (NO). To better understand this
      process, we characterized the vascular injury response in the obese Zucker rat by
      examining the expression of adhesion molecules, the recruitment of inflammatory
      cells, and the development of intimal hyperplasia. We also evaluated the ability
      of exogenous NO to inhibit the sequela of vascular injury in the metabolic
      syndrome. Obese and lean Zucker rats underwent carotid artery balloon injury.
      ICAM-1 and P-selectin expression were increased following injury in the obese
      animals compared with the lean rats. The obese rats also responded with increased
      macrophage infiltration of the vascular wall as well as increased neointima
      formation compared with their lean counterparts (intima/media = 0.91 vs. 0.52, P
      = 0.001). After adenovirus-mediated inducible NO synthase (iNOS) gene transfer,
      ICAM-1, P-selectin, inflammatory cell influx, and oxidized low-density
      lipoprotein (LDL) receptor expression were all markedly reduced versus injury
      alone. iNOS gene transfer also significantly inhibited proliferative activity
      (54% and 73%; P < 0.05) and neointima formation (53% and 67%; P < 0.05) in lean
      and obese animals, respectively. The vascular injury response in the face of
      obesity and the metabolic syndrome is associated with increased adhesion molecule
      expression, inflammatory cell infiltration, oxidized LDL receptor expression, and
      proliferation. iNOS gene transfer is able to effectively inhibit this heightened
      injury response and reduce neointima formation in this proinflammatory
      environment.

PMID- 15734884
TI  - EGF receptor-dependent JNK activation is involved in arsenite-induced
      p21Cip1/Waf1 upregulation and endothelial apoptosis.
AB  - Arsenic exposure is associated with an increased risk of atherosclerosis and
      vascular diseases. Although endothelial cells have long been considered to be the
      primary targets of arsenic toxicity, the underlying molecular mechanism remains
      largely unknown. In this study, we sought to explore the signaling pathway
      triggered by sodium arsenite and its implication for endothelial phenotype. We
      found that sodium arsenite produced time- and dose-dependent decreases in human
      umbilical vein endothelial cell viability. This effect correlated with the
      induction of p21Cip1/Waf1 (up to 10-fold), a regulatory protein of cell cycle and
      apoptosis. We also found that arsenite-stimulated EGF (ErbB1) and ErbB2 receptor
      transactivation, manifest as receptor tyrosine phosphorylation, appeared to be a
      proximal signaling event leading to p21Cip1/Waf1 induction, because both
      pharmacological inhibitors and knockdown of receptors by RNA interference blocked
      arsenite-induced p21Cip1/Waf1 upregulation. Arsenite-induced activation of JNK
      and p38 MAPK was distinct, with only JNK as a downstream target of the EGF
      receptor. Moreover, inhibition of JNK with SP-600125 or dominant negative MKK7
      inhibited only p21Cip1/Waf1 induction, whereas the p38 MAPK inhibitor SB-203580
      or dominant negative MKK4 inhibited both p21Cip1/Waf1 and p53 induction.
      Functionally, inhibition of p21Cip1/Waf1 induction prevented endothelial
      apoptosis due to arsenite treatment. Insofar as endothelial dysfunction promotes
      vascular disease, these data provide a mechanism for the increased incidence of
      cardiovascular disease due to arsenite exposure.

PMID- 15734885
TI  - Increased tolerance to hypoxic metabolic inhibition and reoxygenation of
      cardiomyocytes from apolipoprotein E-deficient mice.
AB  - Although hypercholesterolemia is a strong risk factor for cardiovascular disease,
      it has in some instances paradoxically been associated with reduced infarct size
      and preserved contractile function in isolated hearts after ischemia and
      reperfusion. To elucidate potential cellular protective mechanisms, myocytes of
      hypercholesterolemic apolipoprotein E-deficient (ApoE-/-) and wild-type mice were
      subjected to hypoxic metabolic inhibition (I) with subsequent reoxygenation (R).
      Intracellular Ca2+ concentration ([Ca2+]i) and pH (pHi) were monitored as well as
      cell length and arrhythmic events. Force measurements in papillary muscles were
      also recorded, and myocardial expression of Na+/H+ exchanger 1 (NHE1) and three
      Ca2+ handling proteins [sarco(endo)plasmic reticulum Ca2+-ATPase, Na+/Ca2+
      exchanger, and plasma membrane Ca2+-ATPase] was quantified. After 30 min of I and
      35 min of R, Ca2+ overload was more pronounced in wild-type cells (P < 0.05). In
      these myocytes, pHi also dropped faster and remained below those values
      determined in ApoE-/- cells (P < 0.05). Furthermore, more wild-type myocytes
      remained in a contracted state (P < 0.05). This group also showed a higher
      incidence of arrhythmic events during R (P < 0.05). No group difference was found
      in the expression of the Ca2+ handling proteins. However, NHE1 protein was
      downregulated in hearts of ApoE-/- mice (P < 0.05). Histological results depict
      hyperplasia in ApoE-/- hearts without atherosclerosis of the coronaries.
      Contractile dysfunction was not observed in papillary muscles from ApoE-/-
      hearts. Our results suggest that downregulated myocardial NHE1 expression in
      hypercholesterolemic ApoE-/- mice could have contributed to increased tolerance
      to I/R. It remains to be elucidated whether NHE1 downregulation is a unique
      feature of these genetically altered animals.

PMID- 15734886
TI  - Diazoxide preserves hypercapnia-induced arteriolar vasodilation after global
      cerebral ischemia in piglets.
AB  - Diazoxide (Diaz), an activator of mitochondrial ATP-sensitive K+ (mitoKATP)
      channels, is neuroprotective, but the mechanism of action is unclear. We tested
      whether Diaz preserves endothelium-dependent (hypercapnia) or -independent
      [iloprost (Ilo)] cerebrovascular dilator responses after ischemia-reperfusion
      (I/R) in newborn pigs and whether the effect of Diaz is sensitive to 5
      hydroxydecanoate (5-HD), an inhibitor of mitoKATP channels. Anesthetized,
      ventilated piglets (n = 48) were equipped with closed cranial windows. Changes in
      diameter of pial arterioles were determined with intravital microscopy in
      response to graded hypercapnia (5-10% CO2 - 21% O2-balance N2, n = 25) or Ilo
      (0.1-1 microg/ml, n = 18) before and 1 h after 10 min of global I/R. Experimental
      groups were pretreated with vehicle, NS-398 (a selective cyclooxygenase-2
      inhibitor, 1 mg/kg), Diaz (3 mg/kg), or 5-HD (20 mg/kg) + Diaz. Potential direct
      effects of Diaz and 5-HD on hypercapnic vasodilation were also tested in the
      absence of I/R (n = 5). To confirm the direct effect of Diaz on mitochondria,
      mitochondrial membrane potential in cultured piglet cerebrovascular endothelial
      cells was monitored using Mito Tracker Red. Hypercapnia resulted in dose
      dependent pial arteriolar vasodilation, which was attenuated by approximately 70%
      after I/R in vehicle- and NS-398-treated animals. Diaz and 5-HD did not affect
      the CO2 response. Diaz significantly preserved the postischemic vasodilation
      response to hypercapnia, but not to Ilo. Diaz depolarized mitochondria in
      cultured piglet cerebrovascular endothelial cells, and 5-HD completely abolished
      the protective effect of Diaz, both findings indicate a role for mitoKATP
      channels. In summary, preservation of arteriolar dilator responsiveness by Diaz
      may contribute to neuroprotection.

PMID- 15734887
TI  - Delineating the guide-wire flow obstruction effect in assessment of fractional
      flow reserve and coronary flow reserve measurements.
AB  - Hemodynamic analysis was conducted to determine uncertainty in clinical
      measurements of coronary flow reserve (CFR) and fractional flow reserve (FFR)
      over pathophysiological conditions in a patient group with coronary artery
      disease during angioplasty. The vasodilation-distal perfusion pressure (CFR
      p(rh)) curve was obtained for 0.35- and 0.46-mm guide wires. Our hypothesis is
      that a guide wire spanning the lesions elevates the pressure gradient and reduces
      the flow during hyperemic measurements. Maximal CFR-p(rh) was uniquely determined
      by the intersection of measured CFR and calculated p(rh) of native and residual
      epicardial lesions in patients without microvascular disease, during angioplasty.
      Extrapolation of the linear curve gave a zero-coronary flow mean pressure (p(zf))
      of approximately 20 mmHg and a corresponding p(rh) of 55 mmHg in the native
      lesions, which coincided with the level that causes ischemia in human hearts. On
      this linear curve, values of CFR and FFRmyo (pathophysiological condition) and
      CFRg and FFRmyog (in the presence of the guide wire) were obtained in native and
      residual lesions. A strong linear correlation was found between CFR and CFRg [CFR
      = CFRg x 0.689 + 1.271 (R2= 0.99) for 0.46 mm and CFR = CFRg x 0.757 + 1.004 (R2=
      0.99) for 0.35 mm] and between FFRmyo and FFRmyog [FFRmyo = FFRmyog x 0.737 +
      0.263 (R2= 0.99) for 0.46 mm and FFRmyo = FFRmyog x 0.790 + 0.210 (R2= 0.99) for
      0.35 mm]. This study establishes a strong correlation between CFR and CFRg and
      between FFRmyo and FFRmyog, which could be used to obtain the true state of
      occlusion in the coronary artery during angioplasty.

PMID- 15734888
TI  - Novel method for measurement of medium size arterial lumen area with an impedance
      catheter: in vivo validation.
AB  - There is no doubt that the transformation of a cardiac catheter into a
      conductance catheter that allows reliable and accurate assessment of lumen cross
      sectional area (CSA) will provide a powerful diagnostic and treatment tool for
      the invasive cardiologist. The objective of this study was to develop a method
      based on the impedance catheter that allows accurate and reproducible
      measurements of CSA for medium size vessels (e.g., coronary, femoral, and carotid
      arteries). Two solutions of NaCl (0.5% and 1.5%) with known conductivities were
      injected directly into the lumen of the artery in eight swine. We showed that the
      CSA can be determined analytically from two Ohm's law-type algebraic equations
      that account for the parallel conductance of the current into the surrounding
      tissue. Excellent agreement was found between the conductance catheter with the
      proposed two-injection method and B-mode ultrasound (US). The root mean square
      error for the impedance measurements was 4.8% of the mean US diameter. The
      repeatability of the technique was assessed with duplicate measurements. The mean
      of the difference between the two measurements was nearly zero, and the
      repeatability coefficient was within 2.4% of the mean of the two measurements.
      The validated method was used to assess the degree of acute vasodilatation of the
      vessel in response to flow overload.

PMID- 15734889
TI  - Electrotonic influences on action potential duration dispersion in small hearts:
      a simulation study.
AB  - Intrinsic spatial variations in repolarization currents in the heart can produce
      spatial gradients in action potential duration (APD) that serve as possible sites
      for conduction block and the initiation of reentrant activity. In well-coupled
      myocardium, however, electrotonic influences at the stimulus site and wavefront
      collision sites act to modulate any intrinsic heterogeneity in APD. These effects
      alter APD gradients over an extent larger than that suggested by the length
      constant associated with propagation and, thus, are hypothesized to play a
      greater role in smaller hearts used as experimental models of human disease. This
      study uses computer simulation to investigate how heart size, tissue properties,
      and the spatial assignment of cell types affect functional APD dispersion.
      Simulations were carried out using the murine ventricular myocyte model of Pandit
      et al. or the Luo-Rudy mammalian model in three-dimensional models of mouse and
      rabbit ventricular geometries. Results show that the spatial extent of the APD
      dispersion is related to the dynamic changes in transmembrane resistance during
      recovery. Also, because of the small dimensions of the mouse heart, electrotonic
      effects on APD primarily determine the functional dispersion of refractoriness,
      even in the presence of large intrinsic cellular heterogeneity and reduced
      coupling. APD dispersion, however, is found to increase significantly when the
      heart size increases to the size of a rabbit heart, unmasking intrinsic cell
      types.

PMID- 15734890
TI  - Loaded wheel running and muscle adaptation in the mouse.
AB  - Voluntary cage wheel exercise has been used extensively to determine the
      physiological adaptation of cardiac and skeletal muscle in mice. In this study,
      we tested the effect of different loading conditions on voluntary cage wheel
      performance and muscle adaptation. Male C57Bl/6 mice were exposed to a cage wheel
      with no-resistance (NR), low-resistance (LR), or high-resistance (HR) loads for 7
      wk. Power output was elevated (3-fold) under increased loading (LR and HR)
      conditions compared with unloaded (NR) exercise training. Only unloaded (NR)
      exercise induced an increase in heart mass, whereas only loaded (LR and HR)
      exercise training induced an increase in skeletal (soleus) muscle mass. Moreover,
      unloaded and loaded exercise training had a differential impact on the cross
      sectional area of muscle fibers, depending on the type of myosin heavy chain
      expressed by each fiber. The biochemical adaptation of the heart was
      characterized by a decrease in genes associated with pathological (but not
      physiological) cardiac hypertrophy and a decrease in calcineurin expression in
      all exercise groups. In addition, transcriptional activity of myocyte enhancer
      factor-2 (MEF-2) was significantly decreased in the hearts of the LR group as
      determined by a MEF-2-dependent transgene driving the expression of beta
      galactosidase. Phosphorylation of glycogen synthase kinase-3beta, protein kinase
      B (Akt), and p70 S6 kinase was increased only in the hearts of the NR group,
      consistent with the significant increase in cardiac mass. In conclusion, unloaded
      and loaded cage wheel exercise have a differential impact on cage wheel
      performance and muscle (cardiac and skeletal) adaptation.

PMID- 15734895
TI  - In utero angiopoietin-2 gene delivery remodels placental blood vessel phenotype:
      a murine model for studying placental angiogenesis.
AB  - Angiopoietin (Ang)-2, the natural antagonist of the Ang1/Tie2 receptor is a
      complex regulator of blood vessel plasticity that plays a pivotal role in both
      vessel sprouting [in the presence of vascular endothelial growth factor (VEGF)-A]
      and vessel regression (in the absence of VEGF-A). Based on the spatial and
      temporal expression of Ang2 throughout human gestation, we recently suggested
      that the Ang2 may play a pivotal role in placental angiogenesis. Further, to
      examine this tenet we have developed a novel murine model system in which in
      utero Ang2 gene delivery via a non-replicating adenoviral expression vector has
      the potential to manipulate the blood vessel phenotype in vivo during pregnancy.
      Ang2 overexpression selectively and rapidly remodels the labyrinth perivascular
      extracellular matrix, subsequently promoting plasticity of the maternal and fetal
      vessels, which appear honeycombed due to a 2-fold increase in blood vessel
      luminal area. High levels of Ang2 impair endothelial cell adhesiveness, leading
      to vascular leakiness with perivascular oedema, which increases placental weight.
      These observations suggest that the Ang2 overexpression may play a key role in
      placental vascular remodelling. Furthermore, we suggest a novel new model to
      study the pathobiology of placental vascularization and the effect of placental
      blood vessels on fetal phenotype.

PMID- 15734891
TI  - Upregulation of beta-adrenergic receptors in heart failure due to volume
      overload.
AB  - To examine the mechanisms of changes in beta-adrenergic signal transduction in
      heart failing due to volume overload, we studied the status of beta-adrenoceptors
      (beta-ARs), G protein-coupled receptor kinase (GRK), and beta-arrestin in heart
      failure due to aortocaval shunt (AVS). Heart failure in rats was induced by
      creating AVS for 16 wk, and beta-AR binding, GRK activity, as well as their
      protein content, and mRNA levels were determined in both left and right
      ventricles. The density and protein content for beta1-ARs, unlike those for beta2
      ARs, were increased in the failing hearts. Furthermore, protein contents for GRK
      isoforms and beta-arrestin-1 were decreased in membranous fractions and increased
      in cytosolic fractions from the failing hearts. On the other hand, steady-state
      mRNA levels for beta1-ARs and GRK2, as well as protein content for Gbetagamma
      subunits, did not change in the failing heart. Basal cardiac function was
      depressed; however, both in vivo and ex vivo positive inotropic responses of the
      failing hearts to isoproterenol were augmented. Treatment of AVS animals with
      imidapril (1 mg.kg(-1).day(-1)) or losartan (20 mg.kg(-1).day(-1)) retarded the
      progression of heart failure; partially prevented changes in beta1-ARs, GRKs, and
      beta-arrestin-1 in the failing myocardium; and attenuated the increase in
      positive inotropic effect of isoproterenol. These results indicate that
      upregulation of beta1-ARs is associated with subcellular redistribution of GRKs
      and beta-arrestin-1 in the failing heart due to volume overload. Furthermore,
      attenuation of alterations in beta-adrenergic system by imidapril or losartan may
      be due to blockade of the renin-angiotensin system in the AVS model of heart
      failure.

PMID- 15734896
TI  - Human testicular protein TPX1/CRISP-2: localization in spermatozoa, fate after
      capacitation and relevance for gamete interaction.
AB  - Testicular protein Tpx-1, also known as CRISP-2, is a cysteine-rich secretory
      protein specifically expressed in the male reproductive tract. Since the
      information available on the human protein is limited to the identification and
      expression of its gene, in this work we have studied the presence and
      localization of human Tpx-1 (TPX1) in sperm, its fate after capacitation and
      acrosome reaction (AR), and its possible involvement in gamete interaction.
      Indirect immunofluorescence studies revealed the absence of significant staining
      in live or fixed non-permeabilized sperm, in contrast to a clear labelling in the
      acrosomal region of permeabilized sperm. These results, together with
      complementary evidence from protein extraction procedures strongly support that
      TPX1 would be mainly an intra-acrosomal protein in fresh sperm. After in vitro
      capacitation and ionophore-induced AR, TPX1 remained associated with the
      equatorial segment of the acrosome. The lack of differences in the
      electrophoretic mobility of TPX1 before and after capacitation and AR indicates
      that the protein would not undergo proteolytical modifications during these
      processes. The possible involvement of TPX1 in gamete interaction was evaluated
      by the hamster oocyte penetration test. The presence of anti-TPX1 during gamete
      co-incubation produced a significant and dose-dependent inhibition in the
      percentage of penetrated zona-free hamster oocytes without affecting sperm
      motility, the AR or sperm binding to the oolema. Together, these results indicate
      that human TPX1 would be a component of the sperm acrosome that remains
      associated with sperm after capacitation and AR, and is relevant for sperm-oocyte
      interaction.

PMID- 15734897
TI  - A deletion of a novel heat shock gene on the Y chromosome associated with
      azoospermia.
AB  - Deletions of the Y chromosome are a significant cause of spermatogenic failure.
      Three major deletion intervals have been defined and termed AZFa, AZFb and AZFc.
      Here, we report an unusual case of a proximal AZFb deletion that includes the Y
      chromosome palindromic sequence P4 and a novel heat shock factor (HSFY). This
      deletion neither include the genes EIF1AY, RPS4Y2 nor copies of the RBMY1 genes.
      The individual presented with idiopathic azoospermia. We propose that deletions
      of the testis-specific HSFY gene family may be a cause of unexplained cases of
      idiopathic male infertility. This deletion would not have been detected using
      current protocols for Y chromosome microdeletion screens, therefore we recommend
      that current screening protocols be extended to include this region and other
      palindrome sequences that contain genes expressed specifically in the testis.

PMID- 15734898
TI  - Immunophenotypical characterization of contractile cells in caput epididymidis of
      men affected by congenital or post-inflammatory obstructive azoospermia.
AB  - Myoid cells of the human caput epididymidis are replaced by large cells with
      ultrastructural features of smooth muscle cells (SMC) in chronic obstruction of
      the male genital tract. To evaluate whether these cellular changes are associated
      with different functional phenotypes we analysed the immunohistochemical
      expression of myosin heavy chain isoforms and of extracellular matrix (EM)
      components in the human caput epididymidis contractile cells in normal and in
      obstructed epididymides. Normal caput epididymidis myoid cells expressed a
      scattered immunostaining for SM2, marker of differentiated contractile SMC, while
      no staining was detected for SMemb (the non-muscle-type myosin heavy chain
      isoform) and for its transcription factor BTEB2, markers of undifferentiated
      proliferating SMC. A faint immunoreaction (IR) for EM was observed in the
      peritubular wall of the normal caput. In the contractile wall of the obstructed
      caput epididymidis a strong IR was detected for all myosin heavy chain isoforms
      as well as for collagen type IV and for fibronectin, markers for a secretory
      function of SMC. These findings, unknown in other models of SMC pathophysiology,
      suggest that myoid cells resume the molecular machinery of both mature SMC and of
      differentiating/secretory cells in the chronic obstruction of the human caput.
      Contractile cells of the epididymal duct represent a unique model to study the
      plasticity of SMC.

PMID- 15734899
TI  - Relative bioavailability of calcium from calcium formate, calcium citrate, and
      calcium carbonate.
AB  - Calcium is an essential nutrient required in substantial amounts, but many diets
      are deficient in calcium making supplementation necessary or desirable. The
      objective of this study was to compare the oral bioavailability of calcium from
      calcium formate, a new experimental dietary calcium supplement, to that of
      calcium citrate and calcium carbonate. In a four-way crossover study, either a
      placebo or 1200 mg of calcium as calcium carbonate, calcium citrate, or calcium
      formate were administered orally to 14 healthy adult female volunteers who had
      fasted overnight. After calcium carbonate, the maximum rise in serum calcium (
      approximately 4%) and the fall in serum intact parathyroid hormone 1-84 (iPTH)
      (approximately 20-40%) did not differ significantly from placebo. After calcium
      citrate, the changes were modestly but significantly (p < 0.05) greater, but only
      at 135 to 270 min after ingestion. In contrast, within 60 min after calcium
      formate serum calcium rose by approximately 15% and serum iPTH fell by 70%. The
      mean increment in area under the plasma concentration-time curve (0-270 min) for
      serum calcium after calcium formate (378 mg . min/dl) was double that for calcium
      citrate (178 mg . min/dl; p < 0.01), whereas the latter was only modestly greater
      than either placebo (107; p < 0.05) or calcium carbonate (91; p < 0.05). In this
      study, calcium formate was clearly superior to both calcium carbonate and calcium
      citrate in ability to deliver calcium to the bloodstream after oral
      administration. Calcium formate may offer significant advantages as a dietary
      calcium supplement.

PMID- 15734900
TI  - Comparison of the antinociceptive profiles of gabapentin and 3-methylgabapentin
      in rat models of acute and persistent pain: implications for mechanism of action.
AB  - The anticonvulsant gabapentin (GBP) has been shown effective for the treatment of
      neuropathic pain, although its mechanism of action remains unclear. A recent
      report has suggested that binding to the alpha(2)delta subunit of voltage-gated
      calcium channels contributes to its antinociceptive effect, based on the
      stereoselective efficacy of two analogs: (1S,3R)3-methylgabapentin (3-MeGBP)
      (IC(50) = 42 nM), which is effective in neuropathic pain models; and (1R,3R)3
      MeGBP (IC(50) > 10,000 nM), which is ineffective (Field et al., 2000). The
      present study was designed to further examine the profiles of GBP and 3-MeGBP in
      rat models of acute and persistent pain. Systemic administration of GBP or
      (1S,3R)3-MeGBP inhibited tactile allodynia in the spinal nerve ligation model of
      neuropathic pain, whereas (1R,3R)3-MeGBP was ineffective. The antiallodynic
      effect of GBP, but not (1S,3R)3-MeGBP, was blocked by i.t. injection of the
      GABA(B) receptor antagonist [3-[[(3,4
      dichlorophenyl)methyl]amino]propyl](diethoxymethyl)phosphinic acid (CGP52432).
      Systemic GBP or (1S,3R)3-MeGBP also inhibited the second phase of formalin-evoked
      nociceptive behaviors, whereas (1R,3R)3-MeGBP was ineffective. However, both
      (1S,3R)3-MeGBP and (1R,3R)3-MeGBP, but not GBP, inhibited first phase behaviors.
      In the carrageenan model of inflammatory pain, systemic GBP or (1R,3R)3-MeGBP
      failed to inhibit thermal hyperalgesia, whereas (1S,3R)3-MeGBP had a significant,
      albeit transient, effect. Systemic (1S,3R)3-MeGBP, but not GBP or (1R,3R)3-MeGBP,
      also produced an antinociceptive effect in the warm water tail withdrawal test of
      acute pain. These data demonstrate that GBP and 3-MeGBP display different
      antinociceptive profiles, suggesting dissimilar mechanisms of antinociceptive
      action. Thus, the stereoselective efficacy of 3-MeGBP, presumably related to
      alpha(2)delta binding, likely does not completely account for the mechanism of
      action of GBP.

PMID- 15734901
TI  - The cardioprotective effects of preconditioning with endotoxin, but not ischemia,
      are abolished by a peroxisome proliferator-activated receptor-gamma antagonist.
AB  - We investigated whether endogenous ligands of peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) protect the heart against ischemia-reperfusion (I/R)
      injury. The selective PPAR-gamma antagonist GW9662 (2-chloro-5-nitrobenzanilide)
      was used in rat models of 1) regional myocardial I/R, 2) ischemic
      preconditioning, and 3) delayed cardioprotection by endotoxin. We also
      investigated the effects of the selective cyclooxygenase-2 inhibitor, parecoxib,
      on ischemic preconditioning and delayed cardioprotective effects of endotoxin.
      Male Wistar rats were anesthetized with sodium thiopentone. Animals were
      subjected to either 15 or 25 min of regional myocardial I/R and pretreated with
      the PPAR-gamma agonist ciglitazone (0.3 mg/kg), the PPAR-gamma antagonist GW9662
      (1 mg/kg), or GW9662 and ciglitazone. Animals were also subjected to either 1)
      ischemic preconditioning alone, ischemic preconditioning, and pretreated with
      either GW9662 or parecoxib (20 mg/kg) or 2) lipopolysaccharide (LPS) (1 mg/kg)
      alone, LPS, and pretreated with ciglitazone, GW9662, or parecoxib (20 mg/kg).
      Myocardial infarct size was determined by p-nitroblue tetrazolium staining. The
      PPAR-gamma antagonist GW9662 (1 mg/kg) abolished the cardioprotection afforded by
      the potent PPAR-gamma agonist ciglitazone (0.3 mg/kg). Neither GW9662 nor
      parecoxib affected the cardioprotective effects of ischemic preconditioning.
      Pretreatment with ciglitazone did not provide additional cardioprotection to LPS
      treated animals. Both GW9662 and parecoxib abolished the delayed cardioprotective
      effects of endotoxin. Thus, we propose that 1) endogenous ligands of PPAR-gamma
      are being generated by myocardial ischemia in sufficient amounts to attenuate
      myocardial I/R injury, and 2) that cyclooxygenase-2 metabolites contribute to (or
      even account for) the cardioprotective effects of endotoxin (second window of
      protection) by acting as endogenous PPAR-gamma ligands.

PMID- 15734902
TI  - Cilostazol reduces atherosclerosis by inhibition of superoxide and tumor necrosis
      factor-alpha formation in low-density lipoprotein receptor-null mice fed high
      cholesterol.
AB  - This study shows that 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro
      2(1H)-quinolinone (cilostazol) suppresses the atherosclerotic lesion formation in
      the low-density lipoprotein receptor (Ldlr)-null mice. Ldlr-null mice fed a high
      cholesterol diet showed multiple plaque lesions in the proximal ascending aorta
      including aortic sinus, accompanied by increased macrophage accumulation with
      increased expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte
      chemoattractant protein-1 (MCP-1). Supplementation of cilostazol (0.2% w/w) in
      diet significantly decreased the plaque lesions with reduced macrophage
      accumulation and suppression of VCAM-1 and MCP-1 in situ. Increased superoxide
      and tumor necrosis factor-alpha (TNF-alpha) production were significantly lowered
      by cilostazol in situ as well as in cultured human umbilical vein endothelial
      cells (HUVECs). TNF-alpha-induced increased inhibitory kappaBalpha degradation in
      the cytoplasm and nuclear factor-kappaB (NF-kappaB) p65 activation in the nuclei
      of HUVECs were reversed by cilostazol (1 approximately 100 microM) as well as by
      (E)-3[(4-t-butylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7085) (10 microM),
      suggesting that cilostazol strongly inhibits NF-kappaB activation and p65
      translocation into the nuclei. Furthermore, in gel shift and DNA-binding assay,
      cilostazol inhibited NF-kappaB/DNA complex and nuclear DNA-binding activity of
      the NF-kappaB in the nuclear extracts of the RAW 264.7 cells. Taken together, it
      is suggested that the anti-atherogenic effect of cilostazol in cholesterol-fed
      Ldlr-null mice is ascribed to its property to suppress superoxide and TNF-alpha
      formation, and thereby reducing NF-kappaB activation/transcription, VCAM-1/MCP-1
      expressions, and monocyte recruitments.

PMID- 15734903
TI  - Differential regulation of FLOWERING LOCUS C expression by vernalization in
      cabbage and Arabidopsis.
AB  - Vernalization is required to induce flowering in cabbage (Brassica oleracea var
      Capitata L.). Since FLOWERING LOCUS C (FLC) was identified as a major repressor
      of flowering in the vernalization pathway in Arabidopsis (Arabidopsis thaliana),
      two homologs of AtFLC, BoFLC3-2 and BoFLC4-1, were isolated from cabbage to
      investigate the molecular mechanism of vernalization in cabbage flowering. In
      addition to the sequence homology, the genomic organization of cabbage FLC is
      similar to that of AtFLC, except that BoFLC has a relatively smaller intron 1
      compared to that of AtFLC. A vernalization-mediated decrease in FLC transcript
      level was correlated with an increase in FT transcript level in the apex of
      cabbage. This observation is in agreement with the down-regulation of FT by FLC
      in Arabidopsis. Yet, unlike that in Arabidopsis, the accumulation of cabbage FLC
      transcript decreased after cold treatment of leafy plants but not imbibed seeds,
      which is consistent with the promotion of cabbage flowering by vernalizing adult
      plants rather than seeds. To further dissect the different regulation of FLC
      expression between seed-vernalization-responsive species (e.g. Arabidopsis) and
      plant-vernalization-responsive species (e.g. cabbage), the pBoFLC4-1BoFLC4-1GUS
      construct was introduced into Arabidopsis to examine its vernalization response.
      Down-regulation of the BoFLC4-1GUS construct by seed vernalization was unstable
      and incomplete; in addition, the expression of BoFLC4-1GUS was not suppressed by
      vernalization of transgenic rosette-stage Arabidopsis plants. We propose a
      hypothesis to illustrate the distinct mechanism by which vernalization regulates
      the expression of FLC in cabbage and Arabidopsis.

PMID- 15734904
TI  - Proteomic identification of S-nitrosylated proteins in Arabidopsis.
AB  - Although nitric oxide (NO) has grown into a key signaling molecule in plants
      during the last few years, less is known about how NO regulates different events
      in plants. Analyses of NO-dependent processes in animal systems have demonstrated
      protein S-nitrosylation of cysteine (Cys) residues to be one of the dominant
      regulation mechanisms for many animal proteins. For plants, the principle of S
      nitrosylation remained to be elucidated. We generated S-nitrosothiols by treating
      extracts from Arabidopsis (Arabidopsis thaliana) cell suspension cultures with
      the NO-donor S-nitrosoglutathione. Furthermore, Arabidopsis plants were treated
      with gaseous NO to analyze whether S-nitrosylation can occur in the specific
      redox environment of a plant cell in vivo. S-Nitrosylated proteins were detected
      by a biotin switch method, converting S-nitrosylated Cys to biotinylated Cys.
      Biotin-labeled proteins were purified and analyzed using nano liquid
      chromatography in combination with mass spectrometry. We identified 63 proteins
      from cell cultures and 52 proteins from leaves that represent candidates for S
      nitrosylation, including stress-related, redox-related, signaling/regulating,
      cytoskeleton, and metabolic proteins. Strikingly, many of these proteins have
      been identified previously as targets of S-nitrosylation in animals. At the
      enzymatic level, a case study demonstrated NO-dependent reversible inhibition of
      plant glyceraldehyde-3-phosphate dehydrogenase, suggesting that this enzyme could
      be affected by S-nitrosylation. The results of this work are the starting point
      for further investigation to get insight into signaling pathways and other
      cellular processes regulated by protein S-nitrosylation in plants.

PMID- 15734905
TI  - Water stress deforms tracheids peripheral to the leaf vein of a tropical conifer.
AB  - Just as a soggy paper straw is prone to yielding under the applied suction of a
      thirsty drinker, the xylem tracheids in leaves seem prone to collapse as water
      potential declines, impeding their function. Here we describe the collapse, under
      tension, of lignified cells peripheral to the leaf vein of a broad-leaved
      rainforest conifer, Podocarpus grayi de Laub. Leaves of Podocarpus are
      characterized by an array of cylindrical tracheids aligned perpendicular to the
      leaf vein, apparently involved in the distribution of water radially through the
      mesophyll. During leaf desiccation the majority of these tracheids collapsed from
      circular to flat over the water potential range -1.5 to -2.8 MPa. An increase in
      the percentage of tracheids collapsed during imposed water stress was mirrored by
      declining leaf hydraulic conductivity (K(leaf)), implying a direct effect on
      water transport efficiency. Stomata responded to water stress by closing at -2.0
      MPa when 45% of cells were collapsed and K(leaf) had declined by 25%. This was
      still substantially before the initial indications of cavitation-induced loss of
      hydraulic conductance in the leaf vein, at -3 MPa. Plants droughted until 49% of
      tracheids had collapsed were found to fully recover tracheid shape and leaf
      function 1 week after rewatering. A simple mechanical model of tracheid collapse,
      derived from the theoretical buckling pressure for pipes, accurately predicted
      the collapse dynamics observed in P. grayi, substantiating estimates of cell wall
      elasticity and measured leaf water potential. The possible adaptive advantages of
      collapsible vascular tissue are discussed.

PMID- 15734906
TI  - A novel dwarfing mutation in a green revolution gene from Brassica rapa.
AB  - Mutations in the biosynthesis or signaling pathways of gibberellin (GA) can cause
      dwarfing phenotypes in plants, and the use of such mutations in plant breeding
      was a major factor in the success of the Green Revolution. DELLA proteins are GA
      signaling repressors whose functions are conserved in different plant species.
      Recent studies show that GA promotes stem growth by causing degradation of DELLA
      proteins via the ubiquitin-proteasome pathway. The most widely utilized dwarfing
      alleles in wheat (Triticum aestivum; e.g. Rht-B1b and Rht-D1b) encode GA
      resistant forms of a DELLA protein that function as dominant and constitutively
      active repressors of stem growth. All of the previously identified dominant DELLA
      repressors from several plant species contain N-terminal mutations. Here we
      report on a novel dwarf mutant from Brassica rapa (Brrga1-d) that is caused by
      substitution of a conserved amino acid in the C-terminal domain of a DELLA
      protein. Brrga1-d, like N-terminal DELLA mutants, retains its repressor function
      and accumulates to high levels, even in the presence of GA. However, unlike wild
      type and N-terminal DELLA mutants, Brrga1-d does not interact with a protein
      component required for degradation, suggesting that the mutated amino acid causes
      dwarfism by preventing an interaction needed for its degradation. This novel
      mutation confers nondeleterious dwarf phenotypes when transferred to Arabidopsis
      (Arabidopsis thaliana) and oilseed rape (Brassica napus), indicating its
      potential usefulness in other crop species.

PMID- 15734907
TI  - Control of sodium transport in durum wheat.
AB  - In many species, salt sensitivity is associated with the accumulation of sodium
      (Na(+)) in photosynthetic tissues. Na(+) uptake to leaves involves a series of
      transport steps and so far very few candidate genes have been implicated in the
      control of these processes. In this study, Na(+) transport was compared in two
      varieties of durum wheat (Triticum turgidum) L. subsp. durum known to differ in
      salt tolerance and Na(+) accumulation; the relatively salt tolerant landrace line
      149 and the salt sensitive cultivar Tamaroi. Genetic studies indicated that these
      genotypes differed at two major loci controlling leaf blade Na(+) accumulation
      (R. Munns, G.J. Rebetzke, S. Husain, R.A. James, R.A. Hare [2003] Aust J Agric
      Res 54: 627-635). The physiological traits determined by these genetic
      differences were investigated using measurements of unidirectional (22)Na(+)
      transport and net Na(+) accumulation. The major differences in Na(+) transport
      between the genotypes were (1) the rate of transfer from the root to the shoot
      (xylem loading), which was much lower in the salt tolerant genotype, and (2) the
      capacity of the leaf sheath to extract and sequester Na(+) as it entered the
      leaf. The genotypes did not differ significantly in unidirectional root uptake of
      Na(+) and there was no evidence for recirculation of Na(+) from shoots to roots.
      It is likely that xylem loading and leaf sheath sequestration are separate
      genetic traits that interact to control leaf blade Na(+).

PMID- 15734908
TI  - A genome-wide analysis of the effects of sucrose on gene expression in
      Arabidopsis seedlings under anoxia.
AB  - Exogenous sucrose (Suc) greatly enhances anoxia tolerance of Arabidopsis
      (Arabidopsis thaliana) seedlings. We used the Affymetrix ATH1 GeneChip containing
      more than 22,500 probe sets to explore the anaerobic transcriptome of Arabidopsis
      seedlings kept under anoxia for 6 h in presence or absence of exogenous Suc.
      Functional clustering was performed using the MapMan software. Besides the
      expected induction of genes encoding enzymes involved in Suc metabolism and
      alcoholic fermentation, a large number of genes not related to these pathways
      were affected by anoxia. Addition of exogenous Suc mitigated the effects of
      anoxia on auxin responsive genes that are repressed under oxygen deprivation.
      Anoxia-induced Suc synthases showed a lower induction in presence of exogenous
      Suc, suggesting that induction of these genes might be related to an anoxia
      dependent sugar starvation. Anoxic induction of genes coding for heat shock
      proteins was much stronger in presence of exogenous Suc. Interestingly, a short
      heat treatment enhanced anoxia tolerance, suggesting that heat shock proteins may
      play a role in survival to low oxygen. These results provide insight into the
      effects of Suc on the anoxic transcriptome and provide a list of candidate genes
      that enhance anoxia tolerance of Suc-treated seedlings.

PMID- 15734909
TI  - The potassium transporter AtHAK5 functions in K(+) deprivation-induced high
      affinity K(+) uptake and AKT1 K(+) channel contribution to K(+) uptake kinetics
      in Arabidopsis roots.
AB  - Potassium is an important macronutrient and the most abundant cation in plants.
      Because soil mineral conditions can vary, plants must be able to adjust to
      different nutrient availabilities. Here, we used Affymetrix Genechip microarrays
      to identify genes responsive to potassium (K(+)) deprivation in roots of mature
      Arabidopsis (Arabidopsis thaliana) plants. Unexpectedly, only a few genes were
      changed in their expression level after 6, 48, and 96 h of K(+) starvation even
      though root K(+) content was reduced by approximately 60%. AtHAK5, a potassium
      transporter gene from the KUP/HAK/KT family, was most consistently and strongly
      up-regulated in its expression level across 48-h, 96-h, and 7-d K(+) deprivation
      experiments. AtHAK5 promoter-beta-glucuronidase and -green fluorescent protein
      fusions showed AtHAK5 promoter activity in the epidermis and vasculature of K(+)
      deprived roots. Rb(+) uptake kinetics in roots of athak5 T-DNA insertion mutants
      and wild-type plants demonstrated the absence of a major part of an inducible
      high-affinity Rb(+)/K(+) (K(m) approximately 15-24 microm) transport system in
      athak5 plants. In comparative analyses, uptake kinetics of the K(+) channel
      mutant akt1-1 showed that akt1-1 roots are mainly impaired in a major transport
      mechanism, with an apparent affinity of approximately 0.9 mm K(+)(Rb(+)). Data
      show adaptation of apparent K(+) affinities of Arabidopsis roots when individual
      K(+) transporter genes are disrupted. In addition, the limited transcriptome-wide
      response to K(+) starvation indicates that posttranscriptional mechanisms may
      play important roles in root adaptation to K(+) availability in Arabidopsis. The
      results demonstrate an in vivo function for AtHAK5 in the inducible high-affinity
      K(+) uptake system in Arabidopsis roots.

PMID- 15734910
TI  - Molecular and biochemical characterization of 2-hydroxyisoflavanone dehydratase.
      Involvement of carboxylesterase-like proteins in leguminous isoflavone
      biosynthesis.
AB  - Isoflavonoids are ecophysiologically active secondary metabolites of the
      Leguminosae and known for health-promoting phytoestrogenic functions. Isoflavones
      are synthesized by 1,2-elimination of water from 2-hydroxyisoflavanones, the
      first intermediate with the isoflavonoid skeleton, but details of this
      dehydration have been unclear. We screened the extracts of repeatedly
      fractionated Escherichia coli expressing a Glycyrrhiza echinata cDNA library for
      the activity to convert a radiolabeled precursor into formononetin (7-hydroxy-4'
      methoxyisoflavone), and a clone of 2-hydroxyisoflavanone dehydratase (HID) was
      isolated. Another HID cDNA was cloned from soybean (Glycine max), based on the
      sequence information in its expressed sequence tag library. Kinetic studies
      revealed that G. echinata HID is specific to 2,7-dihydroxy-4'
      methoxyisoflavanone, while soybean HID has broader specificity to both 4'
      hydroxylated and 4'-methoxylated 2-hydroxyisoflavanones, reflecting the
      structures of isoflavones contained in each plant species. Strikingly, HID
      proteins were members of a large carboxylesterase family, of which plant proteins
      form a monophyletic group and some are assigned defensive functions with no
      intrinsic catalytic activities identified. Site-directed mutagenesis with soybean
      HID protein suggested that the characteristic oxyanion hole and catalytic triad
      are essential for the dehydratase as well as the faint esterase activities. The
      findings, to our knowledge, represent a new example of recruitment of enzymes of
      primary metabolism during the molecular evolution of plant secondary metabolism.

PMID- 15734911
TI  - Aquaporins of the PIP2 class are required for efficient anther dehiscence in
      tobacco.
AB  - Several processes during sexual reproduction in higher plants involve the
      movement of water between cells or tissues. Before flower anthesis, anther and
      pollen dehydration takes place before the release of mature pollen at dehiscence.
      Aquaporins represent a class of proteins that mediates the movement of water over
      cellular membranes. Aquaporins of the plasmamembrane PIP2 family are expressed in
      tobacco (Nicotiana tabacum) anthers and may therefore be involved in the movement
      of water in this organ. To gain more insight into the role these proteins may
      play in this process, we have analyzed their localization using
      immunolocalizations and generated plants displaying RNA interference of PIP2
      aquaporins. Our results indicate that PIP2 protein expression is modulated during
      anther development. Furthermore, in tobacco PIP2 RNA interference plants, anther
      dehydration was slower, and dehiscence occurred later when compared with control
      plants. Together, our results suggest that aquaporins of the PIP2 class are
      required for efficient anther dehydration prior to dehiscence.

PMID- 15734912
TI  - Global transcription profiling reveals comprehensive insights into hypoxic
      response in Arabidopsis.
AB  - Plants have evolved adaptation mechanisms to sense oxygen deficiency in their
      environments and make coordinated physiological and structural adjustments to
      enhance their hypoxic tolerance. To gain insight into how plants respond to low
      oxygen stress, gene expression profiling using whole-genome DNA amplicon
      microarrays was carried out at seven time points over 24 h, in wild-type and
      transgenic P(SAG12):ipt Arabidopsis (Arabidopsis thaliana) plants under normoxic
      and hypoxic conditions. Transcript levels of genes involved in glycolysis and
      fermentation pathways, ethylene synthesis and perception, calcium signaling,
      nitrogen utilization, trehalose metabolism, and alkaloid synthesis were
      significantly altered in response to oxygen limitation. Analysis based on gene
      ontology assignments suggested a significant down-regulation of genes whose
      functions are associated with cell walls, nucleosome structures, water channels,
      and ion transporters and a significant up-regulation of genes involved in
      transcriptional regulation, protein kinase activity, and auxin responses under
      conditions of oxygen shortage. Promoter analysis on a cluster of up-regulated
      genes revealed a significant overrepresentation of the AtMYB2-binding motif (GT
      motif), a sugar response element-like motif, and a G-box-related sequence, and
      also identified several putative anaerobic response elements. Finally,
      quantitative real-time polymerase chain reactions using 29 selected genes
      independently verified the microarray results. This study represents one of the
      most comprehensive analyses conducted to date investigating hypoxia-responsive
      transcriptional networks in plants.

PMID- 15734913
TI  - Constitutively elevated salicylic acid signals glutathione-mediated nickel
      tolerance in Thlaspi nickel hyperaccumulators.
AB  - Progress is being made in understanding the biochemical and molecular basis of
      nickel (Ni)/zinc (Zn) hyperaccumulation in Thlaspi; however, the molecular
      signaling pathways that control these mechanisms are not understood. We observed
      that elevated concentrations of salicylic acid (SA), a molecule known to be
      involved in signaling induced pathogen defense responses in plants, is a strong
      predictor of Ni hyperaccumulation in the six diverse Thlaspi species
      investigated, including the hyperaccumulators Thlaspi goesingense, Thlaspi
      rosulare, Thlaspi oxyceras, and Thlaspi caerulescens and the nonaccumulators
      Thlaspi arvense and Thlaspi perfoliatum. Furthermore, the SA metabolites
      phenylalanine, cinnamic acid, salicyloyl-glucose, and catechol are also elevated
      in the hyperaccumulator T. goesingense when compared to the nonaccumulators
      Arabidopsis (Arabidopsis thaliana) and T. arvense. Elevation of free SA levels in
      Arabidopsis, both genetically and by exogenous feeding, enhances the specific
      activity of serine acetyltransferase, leading to elevated glutathione and
      increased Ni resistance. Such SA-mediated Ni resistance in Arabidopsis
      phenocopies the glutathione-based Ni tolerance previously observed in Thlaspi,
      suggesting a biochemical linkage between SA and Ni tolerance in this genus.
      Intriguingly, the hyperaccumulator T. goesingense also shows enhanced sensitivity
      to the pathogen powdery mildew (Erysiphe cruciferarum) and fails to induce SA
      biosynthesis after infection. Nickel hyperaccumulation reverses this pathogen
      hypersensitivity, suggesting that the interaction between pathogen resistance and
      Ni tolerance and hyperaccumulation may have played a critical role in the
      evolution of metal hyperaccumulation in the Thlaspi genus.

PMID- 15734914
TI  - Diatom plastids possess a phosphoribulokinase with an altered regulation and no
      oxidative pentose phosphate pathway.
AB  - The chloroplast enzyme phosphoribulokinase (PRK; EC 2.7.1.19) is part of the
      Calvin cycle (reductive pentose phosphate pathway) responsible for CO(2) fixation
      in photosynthetic organisms. In green algae and vascular plants, this enzyme is
      light regulated via reversible reduction by reduced thioredoxin. We have
      sequenced and characterized the gene of the PRK from the marine diatom Odontella
      sinensis and found that the enzyme has the conserved cysteine residues necessary
      for thioredoxin-dependent regulation. Analysis of enzymatic activity of partially
      purified diatom enzyme and of purified protein obtained by native overexpression
      in Escherichia coli, however, revealed that under natural redox conditions the
      diatom enzyme is generally active. Treatment of the enzyme with strong oxidants
      results in inhibition of the enzyme, which is reversible by subsequent incubation
      with reducing agents. We determined the redox midpoint potentials of the
      regulatory cysteine in the PRK from O. sinensis in comparison to the respective
      spinach (Spinacia oleracea) enzyme and found a more positive redox potential for
      the diatom PRK, indicating that in vivo this enzyme might not be regulated by
      thioredoxin. We also demonstrate that in protease-treated diatom plastids,
      activities of enzymes of the oxidative pentose phosphate pathway are not
      detectable, thus reducing the need for a tight regulation of the Calvin cycle in
      diatoms. We discuss our results in the context of rearrangements of the
      subcellular compartmentation of metabolic pathways due to the peculiar evolution
      of diatoms by secondary endocytobiosis.

PMID- 15734916
TI  - Conservation and divergence of circadian clock operation in a stress-inducible
      Crassulacean acid metabolism species reveals clock compensation against stress.
AB  - One of the best-characterized physiological rhythms in plants is the circadian
      rhythm of CO(2) metabolism in Crassulacean acid metabolism (CAM) plants, which is
      the focus here. The central components of the plant circadian clock have been
      studied in detail only in Arabidopsis (Arabidopsis thaliana). Full-length cDNAs
      have been obtained encoding orthologs of CIRCADIAN CLOCK-ASSOCIATED1 (CCA1)/LATE
      ELONGATED HYPOCOTYL (LHY), TIMING OF CAB EXPRESSION1 (TOC1), EARLY FLOWERING4
      (ELF4), ZEITLUPE (ZTL), FLAVIN-BINDING KELCH REPEAT F-BOX1 (FKF1), EARLY
      FLOWERING3 (ELF3), and a partial cDNA encoding GIGANTEA in the model stress
      inducible CAM plant, Mesembryanthemum crystallinum (Common Ice Plant). TOC1 and
      LHY/CCA1 are under reciprocal circadian control in a manner similar to their
      regulation in Arabidopsis. ELF4, FKF1, ZTL, GIGANTEA, and ELF3 are under
      circadian control in C(3) and CAM leaves. ELF4 transcripts peak in the evening
      and are unaffected by CAM induction. FKF1 shows an abrupt transcript peak 3 h
      before subjective dusk. ELF3 transcripts appear in the evening, consistent with
      their role in gating light input to the circadian clock. Intriguingly, ZTL
      transcripts do not oscillate in Arabidopsis, but do in M. crystallinum. The
      transcript abundance of the clock-associated genes in M. crystallinum is largely
      unaffected by development and salt stress, revealing compensation of the central
      circadian clock against development and abiotic stress in addition to the well
      known temperature compensation. Importantly, the clock in M. crystallinum is very
      similar to that in Arabidopsis, indicating that such a clock could control CAM
      without requiring additional components of the central oscillator or a novel CAM
      oscillator.

PMID- 15734915
TI  - Carbohydrate-active enzymes involved in the secondary cell wall biogenesis in
      hybrid aspen.
AB  - Wood formation is a fundamental biological process with significant economic
      interest. While lignin biosynthesis is currently relatively well understood, the
      pathways leading to the synthesis of the key structural carbohydrates in wood
      fibers remain obscure. We have used a functional genomics approach to identify
      enzymes involved in carbohydrate biosynthesis and remodeling during xylem
      development in the hybrid aspen Populus tremula x tremuloides. Microarrays
      containing cDNA clones from different tissue-specific libraries were hybridized
      with probes obtained from narrow tissue sections prepared by cryosectioning of
      the developing xylem. Bioinformatic analyses using the sensitive tools developed
      for carbohydrate-active enzymes allowed the identification of 25 xylem-specific
      glycosyltransferases belonging to the Carbohydrate-Active EnZYme families GT2,
      GT8, GT14, GT31, GT43, GT47, and GT61 and nine glycosidases (or
      transglycosidases) belonging to the Carbohydrate-Active EnZYme families GH9,
      GH10, GH16, GH17, GH19, GH28, GH35, and GH51. While no genes encoding either
      polysaccharide lyases or carbohydrate esterases were found among the secondary
      wall-specific genes, one putative O-acetyltransferase was identified. These wood
      specific enzyme genes constitute a valuable resource for future development of
      engineered fibers with improved performance in different applications.

PMID- 15734917
TI  - The regulation of anion loading to the maize root xylem.
AB  - The regulation of anion loading to the shoot in maize (Zea mays) was investigated
      via an electrophysiological characterization of ion conductances in protoplasts
      isolated from the root stele. Two distinct anion conductances were identified. In
      protoplasts from well-watered plants, Z. mays xylem-parenchyma quickly-activating
      anion conductance (Zm-X-QUAC) was the most prevalent conductance and is likely to
      load the majority of NO(3)(-) and Cl(-) ions to the xylem in nonstressed
      conditions. Z. mays xylem-parenchyma inwardly-rectifying anion conductance was
      found at a lower frequency in protoplasts from well-watered plants than Zm-X
      QUAC, was much smaller in magnitude in all observed conditions, and is unlikely
      to be such a major pathway for anion loading into the xylem. Activity of Z. mays
      xylem-parenchyma inwardly-rectifying anion conductance increased following a
      water stress prior to protoplast isolation, but the activity of the putative
      major anion-loading pathway, Zm-X-QUAC, decreased. Addition of abscisic acid
      (ABA) to protoplasts from well-watered plants also inhibited Zm-X-QUAC activity
      within minutes, as did a high free Ca(2+)concentration in the pipette. ABA was
      also seen to activate a Ca(2+)-permeable conductance (Z. mays xylem-parenchyma
      hyperpolarization activated cation conductance) in protoplasts from well-watered
      plants. It is postulated that the inhibition of anion loading into the xylem (an
      important response to a water stress) due to down-regulation of Zm-X-QUAC
      activity is mediated by an ABA-mediated rise in free cytosolic Ca(2+).

PMID- 15734918
TI  - Auxin-dependent cell division and cell elongation. 1-Naphthaleneacetic acid and
      2,4-dichlorophenoxyacetic acid activate different pathways.
AB  - During exponential phase, the tobacco (Nicotiana tabacum) cell line cv Virginia
      Bright Italia-0 divides axially to produce linear cell files of distinct
      polarity. This axial division is controlled by exogenous auxin. We used
      exponential tobacco cv Virginia Bright Italia-0 cells to dissect early auxin
      signaling, with cell division and cell elongation as physiological markers.
      Experiments with 1-naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic
      acid (2,4-D) demonstrated that these 2 auxin species affect cell division and
      cell elongation differentially; NAA stimulates cell elongation at concentrations
      that are much lower than those required to stimulate cell division. In contrast,
      2,4-D promotes cell division but not cell elongation. Pertussis toxin, a blocker
      of heterotrimeric G-proteins, inhibits the stimulation of cell division by 2,4-D
      but does not affect cell elongation. Aluminum tetrafluoride, an activator of the
      G-proteins, can induce cell division at NAA concentrations that are not
      permissive for division and even in the absence of any exogenous auxin. The data
      are discussed in a model where the two different auxins activate two different
      pathways for the control of cell division and cell elongation.

PMID- 15734919
TI  - Proteomic characterization of evolutionarily conserved and variable proteins of
      Arabidopsis cytosolic ribosomes.
AB  - Analysis of 80S ribosomes of Arabidopsis (Arabidopsis thaliana) by use of high
      speed centrifugation, sucrose gradient fractionation, one- and two-dimensional
      gel electrophoresis, liquid chromatography purification, and mass spectrometry
      (matrix-assisted laser desorption/ionization time-of-flight and electrospray
      ionization) identified 74 ribosomal proteins (r-proteins), of which 73 are
      orthologs of rat r-proteins and one is the plant-specific r-protein P3. Thirty
      small (40S) subunit and 44 large (60S) subunit r-proteins were confirmed. In
      addition, an ortholog of the mammalian receptor for activated protein kinase C, a
      tryptophan-aspartic acid-domain repeat protein, was found to be associated with
      the 40S subunit and polysomes. Based on the prediction that each r-protein is
      present in a single copy, the mass of the Arabidopsis 80S ribosome was estimated
      as 3.2 MD (1,159 kD 40S; 2,010 kD 60S), with the 4 single-copy rRNAs (18S, 26S,
      5.8S, and 5S) contributing 53% of the mass. Despite strong evolutionary
      conservation in r-protein composition among eukaryotes, Arabidopsis 80S ribosomes
      are variable in composition due to distinctions in mass or charge of
      approximately 25% of the r-proteins. This is a consequence of amino acid sequence
      divergence within r-protein gene families and posttranslational modification of
      individual r-proteins (e.g. amino-terminal acetylation, phosphorylation). For
      example, distinct types of r-proteins S15a and P2 accumulate in ribosomes due to
      evolutionarily divergence of r-protein genes. Ribosome variation is also due to
      amino acid sequence divergence and differential phosphorylation of the carboxy
      terminus of r-protein S6. The role of ribosome heterogeneity in differential mRNA
      translation is discussed.

PMID- 15734921
TI  - Crystal structures of alfalfa caffeoyl coenzyme A 3-O-methyltransferase.
AB  - Caffeoyl coenzyme A 3-O-methyltransferases (CCoAOMTs) are S-adenosyl-l-methionine
      dependent O-methyltransferases (OMTs) involved in lignin biosynthesis. Plant
      CCoAOMTs belong to a distinct family of OMTs, more closely related to the
      mammalian catechol OMTs than to other plant OMTs. The crystal structure of
      alfalfa (Medicago sativa) CCoAOMT in complex with the reaction products S
      adenosine-l-homocysteine and feruloyl/sinapoyl CoAs presented here belong to a
      structurally and mechanistically distinct family of plant small molecule OMTs.
      These structures provide a new understanding of the substrate preferences and the
      catalytic mechanism accompanying CCoAOMT-mediated O-methylation of CoA-linked
      phenylpropanoid substrates.

PMID- 15734920
TI  - Monoterpene metabolism. Cloning, expression, and characterization of (-)
      isopiperitenol/(-)-carveol dehydrogenase of peppermint and spearmint.
AB  - The essential oils of peppermint (Mentha x piperita) and spearmint (Mentha
      spicata) are distinguished by the oxygenation position on the p-menthane ring of
      the constitutive monoterpenes that is conferred by two regiospecific cytochrome
      P450 limonene-3- and limonene-6-hydroxylases. Following hydroxylation of
      limonene, an apparently similar dehydrogenase oxidizes (-)-trans-isopiperitenol
      to (-)-isopiperitenone in peppermint and (-)-trans-carveol to (-)-carvone in
      spearmint. Random sequencing of a peppermint oil gland secretory cell cDNA
      library revealed a large number of clones that specified redox-type enzymes,
      including dehydrogenases. Full-length dehydrogenase clones were screened by
      functional expression in Escherichia coli using a recently developed in situ
      assay. A single full-length acquisition encoding (-)-trans-isopiperitenol
      dehydrogenase (ISPD) was isolated. The (-)-ISPD cDNA has an open reading frame of
      795 bp that encodes a 265-residue enzyme with a calculated molecular mass of
      27,191. Nondegenerate primers were designed based on the (-)-trans-ISPD cDNA
      sequence and employed to screen a spearmint oil gland secretory cell cDNA library
      from which a 5'-truncated cDNA encoding the spearmint homolog, (-)-trans-carveol
      dehydrogenase, was isolated. Reverse transcription-PCR amplification and RACE
      were used to acquire the remaining 5'-sequence from RNA isolated from oil gland
      secretory cells of spearmint leaf. The full-length spearmint dehydrogenase shares
      >99% amino acid identity with its peppermint homolog and both dehydrogenases are
      capable of utilizing (-)-trans-isopiperitenol and (-)-trans-carveol. These
      isopiperitenol/carveol dehydrogenases are members of the short-chain
      dehydrogenase/reductase superfamily and are related to other plant short-chain
      dehydrogenases/reductases involved in secondary metabolism (lignan biosynthesis),
      stress responses, and phytosteroid biosynthesis, but they are quite dissimilar
      (approximately 13% identity) to the monoterpene reductases of mint involved in (
      )-menthol biosynthesis. The isolation of the genes specifying redox enzymes of
      monoterpene biosynthesis in mint indicates that these genes arose from different
      ancestors and not by simple duplication and differentiation of a common
      progenitor, as might have been anticipated based on the common reaction chemistry
      and structural similarity of the substrate monoterpenes.

PMID- 15734922
TI  - Can MR imaging provide a noninvasive "biopsy" of the heart to measure iron
      levels?

PMID- 15734923
TI  - Small pulmonary emboli: what do we know?

PMID- 15734924
TI  - Technology and practice assessment: in search of a "desirable" statement.

PMID- 15734925
TI  - Perfusion imaging of the liver: current challenges and future goals.
AB  - Improved therapeutic options for hepatocellular carcinoma and metastatic disease
      place greater demands on diagnostic and surveillance tests for liver disease.
      Existing diagnostic imaging techniques provide limited evaluation of tissue
      characteristics beyond morphology; perfusion imaging of the liver has potential
      to improve this shortcoming. The ability to resolve hepatic arterial and portal
      venous components of blood flow on a global and regional basis constitutes the
      primary goal of liver perfusion imaging. Earlier detection of primary and
      metastatic hepatic malignancies and cirrhosis may be possible on the basis of
      relative increases in hepatic arterial blood flow associated with these diseases.
      To date, liver flow scintigraphy and flow quantification at Doppler
      ultrasonography have focused on characterization of global abnormalities.
      Computed tomography (CT) and magnetic resonance (MR) imaging can provide regional
      and global parameters, a critical goal for tumor surveillance. Several challenges
      remain: reduced radiation doses associated with CT perfusion imaging, improved
      spatial and temporal resolution at MR imaging, accurate quantification of tissue
      contrast material at MR imaging, and validation of parameters obtained from
      fitting enhancement curves to biokinetic models, applicable to all perfusion
      methods. Continued progress in this new field of liver imaging may have profound
      implications for large patient groups at risk for liver disease.

PMID- 15734928
TI  - Case 80: splenosis.

PMID- 15734926
TI  - Breast cancer yield for screening mammographic examinations with recommendation
      for short-interval follow-up.
AB  - PURPOSE: To compare cancer yield for screening examinations with recommendation
      for short-interval follow-up after diagnostic imaging work-up versus after
      screening mammography only. MATERIALS AND METHODS: From January 1996 to December
      1999, Breast Imaging Reporting and Data System assessments and recommendations
      were collected prospectively for 1,171,792 screening examinations in 758,015
      women aged 40-89 years at seven mammography registries in Breast Cancer
      Surveillance Consortium. Registries obtained waiver of signed consent or
      collected signed consent in accordance with institutional review boards at each
      location. Diagnosis of invasive cancer or ductal carcinoma in situ within 24
      months of screening examination and tumor stage and size for invasive cancer were
      determined through linkage to pathology database or tumor registry. chi2 test was
      used to determine significant differences between groups. RESULTS: Overall, 5.2%
      of first and 1.7% of subsequent screens included recommendation for short
      interval follow-up, which was similar to likelihood of recommendation for
      diagnostic evaluation (first screens, 4.6%; subsequent, 2.6%). Most
      recommendations for short-interval follow-up were based on screening mammography
      alone (86.2% of first screens, 77.5% of subsequent). Yield of cancer for
      screening examinations with probably benign finding (PBF) and recommendation for
      short-interval follow-up based on screening mammography alone tended to be lower
      than in those with PBF and recommendation for short-interval follow-up after
      additional work-up (first screens: 0.54% vs 0.96%, P=.10; subsequent: 1.50% vs
      1.73%, P=.26). Proportion of stage II and higher disease tended to be higher for
      examinations with PBF and recommendation for short-interval follow-up based on
      screening mammography alone compared with those recommended for short-interval
      follow-up after additional work-up (first screens: 34.7% vs 24.4%, P=.43;
      subsequent: 27.5% vs 19.2%, P=.13). CONCLUSION: Many first screening examinations
      include recommendation for short-interval follow-up based on screening
      mammography alone. Cancer yield for these examinations is low and is lower than
      that with diagnostic work-up prior to short-interval follow-up recommendation.
      Absence of diagnostic work-up prior to short-interval follow-up recommendation
      may result in periodic surveillance of a high proportion of benign lesions.

PMID- 15734929
TI  - Assessing cervical spine stability in obtunded blunt trauma patients: review of
      medical literature.
AB  - PURPOSE: To review the current medical literature on dynamic fluoroscopic and
      magnetic resonance (MR) imaging assessment of cervical spine stability in
      obtunded patients who sustained blunt trauma. MATERIALS AND METHODS: The English
      language literature within the Swetswise and Medline databases was searched for
      articles describing dynamic fluoroscopic or MR imaging assessment of cervical
      spine stability in patients who sustained blunt trauma. Patients with fractures
      or radiographic signs of injury were excluded. The frequencies of purely
      ligamentous injuries, injuries requiring immobilization, and other clinically
      important nonligamentous abnormalities were determined. RESULTS: The frequency of
      isolated cervical ligamentous injuries diagnosed with dynamic fluoroscopy, as
      reported in the literature, was 0.9% (11 of 1166 patients), whereas the reported
      frequency of these injuries diagnosed with MR imaging was 22.7% (125 of 550
      patients). All injuries diagnosed with dynamic fluoroscopy and 101 (80.8%) of
      those diagnosed with MR imaging required continued cervical immobilization. Six
      (60%) of 10 injuries diagnosed with dynamic fluoroscopy and seven (5.6%) of 125
      injuries diagnosed with MR imaging required surgical or halo stabilization. Five
      (2.5%) of the 200 obtunded patients assessed with MR imaging and six (0.5%) of
      the 1166 obtunded patients evaluated with dynamic fluoroscopy required surgery.
      CONCLUSION: Review of the current medical literature provided no clear evidence
      of the superiority of either MR imaging or dynamic fluoroscopy in the diagnosis
      of unstable ligamentous injury, although other relative advantages of MR imaging
      indicate that it is preferred for assessing cervical spine stability in obtunded
      blunt trauma patients.

PMID- 15734930
TI  - Ventilation-perfusion scanning and helical CT in suspected pulmonary embolism:
      meta-analysis of diagnostic performance.
AB  - PURPOSE: To perform meta-analysis of literature about the role of helical
      computed tomography (CT) and ventilation-perfusion (V-P) scanning in detection of
      acute pulmonary embolism (PE) by using summary receiver operating characteristic
      (ROC) curve analysis. MATERIALS AND METHODS: V-P scanning articles published from
      January 1985 to March 2003 and helical CT articles published from January 1990 to
      March 2003 in MEDLINE and EMBASE databases were included if (a) tests were
      performed for evaluation of acute PE, (b) conventional angiography was the
      reference standard, and (c) absolute numbers of true-positive, false-negative,
      true-negative, and false-positive results were available. Sensitivity analysis
      was conducted by excluding articles published before 1995. RESULTS: A total of 12
      articles discussing helical CT and/or V-P scanning were included. With a random
      effects model, pooled sensitivity for helical CT was 86.0% (95% confidence
      interval [CI]: 80.2%, 92.1%), and specificity was 93.7% (95% CI: 91.1%, 96.3%). V
      P scanning yielded low sensitivity of 39.0% (95% CI: 37.3%, 40.8%) but high
      specificity of 97.1% (95% CI: 96.0%, 98.3%) with high probability threshold. V-P
      scanning yielded high sensitivity of 98.3% (95% CI: 97.2%, 99.5%) and low
      specificity of 4.8% (95% CI: 4.7%, 4.9%) with normal threshold. Regression
      coefficients for helical CT angiography were 0.588 (95% CI: -1.55, 2.74) and 4.14
      (95% CI: -0.002, 8.28) versus V-P scanning with high and normal thresholds,
      respectively. Regression coefficients for helical CT angiography were 0.588 (95%
      CI: -1.55, 2.74) and 4.14 (95% CI: -0.002, 8.28) versus V-P scanning with high
      and normal thresholds, respectively. CONCLUSION: Helical CT has greater
      discriminatory power than V-P scanning with normal and/or near-normal threshold
      to exclude PE, while helical CT and V-P scanning with high probability threshold
      had similar discriminatory power in the diagnosis of PE.

PMID- 15734931
TI  - 1/T2 and magnetic susceptibility measurements in a gerbil cardiac iron overload
      model.
AB  - PURPOSE: To measure the transverse relaxation rate (1/T2) and magnetic
      susceptibility of the heart in conditions of iron overload by using magnetic
      resonance (MR) imaging and to correlate these with the tissue iron concentration
      in a gerbil model. MATERIALS AND METHODS: With prior approval by the
      institutional animal care and use committee, iron overload was induced with one
      to 15 weekly subcutaneous injections of iron dextran. Nine gerbils had one to
      five injections, 10 had six to 10, and eight had 13-15. T2 of the whole heart was
      measured ex vivo (n=27), and the magnetic susceptibility of the tissue was
      estimated through measurement of the tissue lysate (n=25). The iron level was
      measured (in milligrams of iron per gram of wet tissue) with chemical analysis
      after MR imaging. While 1/T2 and magnetic susceptibility are not equivalent
      measures of the chemically determined tissue iron level, correlations were
      expected and were identified by using linear regression models. RESULTS: Iron
      concentration range was 0.28-1.95 mg/g wet tissue. Iron concentration was
      strongly correlated with 1/T2 (r=0.92, P <.001, and the root of the mean squares
      error of the linear prediction, epsilonRMS, was 0.17 mg Fe/g wet tissue with a
      repetition time of 700 msec). Iron concentration also was strongly correlated
      with magnetic susceptibility (r=0.90, P <.001, epsilonRMS=0.19 mg Fe/g wet
      tissue). Multiple regression analysis with combined 1/T2 (with repetition time of
      700 msec) and magnetic susceptibility data led to a slight increase in r and
      decrease in epsilon(RMS) (r=0.93, P <.001, epsilonRMS=0.16 mg Fe/g wet tissue).
      CONCLUSION: The results of this animal model study demonstrate that 1/T2 and
      magnetic susceptibility values can be used for estimation of the iron level in
      the heart.

PMID- 15734932
TI  - Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting
      agent on rhabdomyosarcoma in rats.
AB  - PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for
      monitoring tumor response in rats after administration of combretastatin A4
      phosphate. MATERIALS AND METHODS: Study protocol was approved by local ethical
      committee for animal care and use. Rhabdomyosarcomas implanted subcutaneously in
      both flanks of 17 rats were evaluated with 1.5-T MR unit by using four-channel
      wrist coil. Transverse T2-weighted fast spin-echo sequences, T1-weighted spin
      echo sequences before and after gadodiamide administration, and transverse echo
      planar diffusion-weighted MR examinations were performed before, 1 and 6 hours,
      and 2 and 9 days after intraperitoneal injection of vascular targeting agent
      (combretastatin A4 phosphate, 25 mg/kg). Apparent diffusion coefficient (ADC) was
      automatically calculated from diffusion-weighted MR imaging findings. These
      findings were compared with histopathologic results at each time point. For
      statistical analysis, paired Student t tests with Bonferroni correction for
      multiple testing were used. RESULTS: T1-weighted images before combretastatin
      administration showed enhancement of solid tumor tissue but not of central
      necrosis. At 1 and 6 hours after combretastatin injection, enhancement of solid
      tissue disappeared almost completely, with exception of small peripheral rim. At
      2 and 9 days after combretastatin injection, enhancement progressively reappeared
      in tumor periphery. ADC, however, showed decrease early after combretastatin
      injection ([1.26 +/- 0.16]x 10(-3) mm2/sec before, [1.18 +/- 0.17]x 10(-3)
      mm2/sec 1 hour after [P=.0005] and [1.08 +/- 0.14]x 10(-3) mm(2)/sec 6 hours
      after [P=.0007] combretastatin A4 phosphate injection), histologically
      corresponding to vessel congestion and vascular shutdown in periphery but no
      necrosis. An increase of ADC ([1.79 +/- 0.13]x 10(-3) mm2/sec) (P <.0001) 2 days
      after combretastatin A4 phosphate injection was paralleled by progressive
      histologic necrosis. A significant (P <.0001) decrease in ADC 9 days after
      treatment ([1.41 +/- 0.15]x 10(-3) mm2/sec) corresponded to tumor regrowth.
      CONCLUSION: In addition to basic relaxation-weighted MR imaging and
      postgadolinium T1-weighted MR imaging to enable prompt detection of vascular
      shutdown, diffusion-weighted MR imaging was used to discriminate between
      nonperfused but viable and necrotic tumor tissues for early monitoring of
      therapeutic effects of vascular targeting agent.

PMID- 15734933
TI  - Chest radiography with a digital flat-panel detector: experimental receiver
      operating characteristic analysis.
AB  - PURPOSE: To evaluate the influence of different detector radiation doses and peak
      kilovoltage settings on diagnostic performance and radiation dose at
      posteroanterior (PA) chest radiography performed with an amorphous silicon flat
      panel detector (FPD). MATERIALS AND METHODS: All examinations were performed by
      using a digital FPD. PA chest radiographs of an anthropomorphic chest phantom
      were obtained with detector radiation doses of 2.50 microGy (system speed, 400),
      1.56 microGy (speed, 640), and 1.25 microGy (speed, 800) and with peak
      kilovoltage values of 100, 120, and 140 kVp. Four types of simulated lesions
      nodules of different sizes, polylobulated lesions, interstitial-nodular lesions,
      and interstitial-reticular lesions-were superimposed on the phantom. After four
      radiologists assessed all of the images, receiver operating characteristics
      analysis was performed. In addition, the entrance surface dose was measured and
      the effective dose was calculated. RESULTS: Reduced detector dose led to
      significantly decreased diagnostic performance in overall lesion detection (P
      <.05). However, over pulmonary areas only, this effect could not be seen. With
      use of the same kilovoltage values, reducing the detector dose, even to 1.25
      microGy (speed, 800), did not lead to significantly decreased lesion
      detectability. In terms of diagnostic performance and effective dose, 120 kVp was
      the most effective. CONCLUSION: Standard PA chest radiographs should still be
      acquired at a detector dose of 2.50 microGy (speed, 400) with 120 kVp to yield
      the highest diagnostic performance. However, when the present analysis was
      focused on the lung fields only, no significant loss in diagnostic performance
      could be demonstrated, even after a 50% reduction in radiation dose.

PMID- 15734934
TI  - Assessing tumor perfusion and treatment response in rectal cancer with
      multisection CT: initial observations.
AB  - PURPOSE: To use first-pass perfusion computed tomography (CT) to prospectively
      investigate tumor vascularity in rectal cancer and to determine whether any of
      the perfusion parameters would predict tumor response to chemotherapy and
      radiation therapy. MATERIALS AND METHODS: The institutional review board approved
      this study, and informed prior consent was obtained from participants. Perfusion
      CT of rectal cancer was performed with four-section multi-detector row CT in 15
      patients (13 men, two women; mean age, 62.1 years; age range, 46-84 years). Five
      patients with prostate cancer served as controls. All patients with rectal cancer
      underwent 6-8 weeks of chemotherapy and radiation therapy followed by surgery. In
      nine patients, perfusion CT was repeated after completion of chemotherapy and
      radiation therapy. Contrast medium-enhanced dynamic CT was performed with a
      static table position for 45 seconds, and the data were analyzed by using
      commercial software to calculate tissue blood flow (BF), blood volume, mean
      transit time (MTT), and vascular permeability-surface area product. Perfusion
      parameters of normal rectum and tumor were compared. Perfusion parameters before
      and after chemotherapy and radiation therapy were compared. A tumor was
      considered to have responded if its stage at pathologic analysis indicated
      regression compared with the preoperative stage. Baseline perfusion values were
      compared between responders and nonresponders. Statistical analysis was performed
      with the Student t test. RESULTS: Rectal cancer showed higher BF and shorter MTT
      compared with those of normal rectum (P < or =.05). After chemotherapy and
      radiation therapy, tumors showed significant reduction in BF and increase in MTT
      (P < or =.05). There was a significant difference in baseline BF and MTT values
      between responders and nonresponders (P < or =.05). Tumors in three patients with
      high initial BF and short MTT showed poor response. CONCLUSION: Perfusion CT of
      rectal cancer can enable assessment of tumor vascularity and perfusion changes
      that result from chemotherapy and radiation therapy. In this small patient
      sample, tumors with initial high BF and short MTT values tended to respond poorly
      to chemotherapy and radiation therapy.

PMID- 15734935
TI  - Correlation of proton MR spectroscopic imaging with gleason score based on step
      section pathologic analysis after radical prostatectomy.
AB  - PURPOSE: To determine whether hydrogen 1 magnetic resonance (MR) spectroscopic
      imaging can be used to predict aggressiveness of prostate cancer. MATERIALS AND
      METHODS: All patients gave informed consent according to an institutionally
      approved research protocol. A total of 123 patients (median age, 58 years; age
      range, 40-74 years) who underwent endorectal MR imaging and MR spectroscopic
      imaging between January 2000 and December 2002 were included. MR imaging and
      spectroscopy were performed by using combined pelvic phased-array and endorectal
      probe. Water and lipids were suppressed, and phase-encoded data were acquired
      with 6.2-mm resolution. Voxels in the peripheral zone were considered suspicious
      for cancer if (Cho + Cr)/Cit was at least two standard deviations above the
      normal level, where Cho represents choline-containing compounds, Cr represents
      creatine and phosphocreatine, and Cit represents citrate. Correlation between
      metabolite ratio and four Gleason score groups identified at step-section
      pathologic evaluation (3 + 3, 3 + 4, 4 + 3, and > or =4 + 4) was assessed with
      generalized estimating equations. RESULTS: Data from 94 patients were included.
      Pathologic evaluation was used to identify 239 lesions. Overall sensitivity of MR
      spectroscopic imaging was 56% for tumor detection, increasing from 44% in lesions
      with Gleason score of 3 + 3 to 89% in lesions with Gleason score greater than or
      equal to 4 + 4. There was a trend toward increasing (Cho + Cr)/Cit with
      increasing Gleason score in lesions identified correctly with MR spectroscopic
      imaging. Tumor volume assessed with MR spectroscopic imaging increased with
      increasing Gleason score. CONCLUSION: MR spectroscopic imaging measurement of
      prostate tumor (Cho + Cr)/Cit and tumor volume correlate with pathologic Gleason
      score. There is overlap between MR spectroscopic imaging parameters at various
      Gleason score levels, which may reflect methodologic and physiologic variations.
      MR spectroscopic imaging has potential in noninvasive assessment of prostate
      cancer aggressiveness.

PMID- 15734936
TI  - Meniscal tears with fragments displaced in notch and recesses of knee: MR imaging
      with arthroscopic comparison.
AB  - PURPOSE: To retrospectively evaluate magnetic resonance (MR) imaging for the
      depiction of meniscal tears with partially detached meniscal fragments displaced
      in the intercondylar notch or in the meniscal recesses of the knee. MATERIALS AND
      METHODS: The institutional review board required neither its approval nor
      informed patient consent for the retrospective review of patient data; however,
      informed patient consent had been obtained before the MR imaging examinations
      were performed. The presence of meniscal tears with notch and recess fragments
      was determined at MR imaging and at subsequent arthroscopy in 101 consecutive
      knees to determine the value of MR imaging for the depiction of these lesions.
      Initial reports were reviewed to evaluate results of initial interpretations. MR
      images were retrospectively analyzed to determine the value of several MR image
      signs for the detection of displaced tears with notch or recess fragments.
      RESULTS: At arthroscopy, 37 (41%) of 91 torn menisci had partially detached
      fragments. Twenty-six torn menisci had notch fragments, and 14 had recess
      fragments; three torn menisci had one notch and one recess fragment each. At
      initial MR image analysis, 38 (36%) of 105 torn menisci had partially detached
      fragments. Twenty-eight torn menisci had notch fragments, and 13 had recess
      fragments; one torn meniscus had two recess fragments, and three torn menisci had
      one notch and one recess fragment each. At initial analysis, sensitivities and
      specificities were, respectively, 69% and 94% for detection of tears with notch
      fragments and 71% and 98% for detection of tears with recess fragments. At
      retrospective analysis of sagittal MR images, the presence of at least one sign
      indicative of meniscal tear with a notch fragment had sensitivities and
      specificities, respectively, of 65% and 78% for observer 1 and 77% and 73% for
      observer 2. The presence of at least one sign indicative of a meniscal tear with
      a recess fragment had sensitivities and specificities, respectively, of 64% and
      77% for observer 1 and 64% and 76% for observer 2. CONCLUSION: Meniscal tears
      with notch and recess fragments are frequently seen at arthroscopy and can be
      depicted at knee MR imaging with moderate sensitivity and high specificity.

PMID- 15734937
TI  - Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive
      impairment measured with arterial spin-labeling MR imaging: initial experience.
AB  - PURPOSE: To prospectively determine if pulsed arterial spin-labeling perfusion
      magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in
      subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI),
      compared with perfusion in cognitively normal (CN) subjects, that is consistent
      with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and
      hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography
      (SPECT) studies of similar populations. MATERIALS AND METHODS: Institutional
      review board approval and informed consent were obtained. Twenty subjects with AD
      (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women;
      mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9
      years) underwent arterial spin-labeling and volumetric T1-weighted structural MR
      imaging. Perfusion images were coregistered to structural images, corrected for
      partial volume effects (PVEs) with information from the structural image to
      determine tissue content of perfusion voxels, and normalized to a study-specific
      template. Analyses of perfusion differences between groups, with and without
      corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed
      fixed-effects analysis of covariance model adjusted for age. In addition, tests
      were performed with and without accounting for global perfusion. RESULTS: The AD
      group showed significant regional hypoperfusion, compared with the CN group, in
      the right inferior parietal cortex extending into the bilateral posterior
      cingulate gyri (P <.001), bilateral superior and middle frontal gyri (P <.001),
      and left inferior parietal lobe (P=.007). When PVEs from underlying cortical gray
      matter atrophy were accounted for, the AD group still showed hypoperfusion in the
      right inferior parietal lobe extending into the bilateral posterior cingulate
      gyri (P <.001) and left (P=.003) and right (P=.012) middle frontal gyri. With a
      more liberal voxel-level threshold of P <.01, the MCI group showed significant
      regional hypoperfusion relative to the CN group in the inferior right parietal
      lobe (P=.046), similar to the region of greatest significance in the AD group.
      CONCLUSION: Arterial spin-labeling MR imaging showed regional hypoperfusion with
      AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of
      similar populations; this hypoperfusion persists after accounting for underlying
      cortical gray matter atrophy.

PMID- 15734938
TI  - Normal FDG distribution patterns in the head and neck: PET/CT evaluation.
AB  - PURPOSE: To retrospectively evaluate the distribution of fluorine 18
      fluorodeoxyglucose (FDG) in the head and neck region with combined positron
      emission tomography-computed tomography (PET/CT) in patients with no known
      abnormality in this region. MATERIALS AND METHODS: The institutional review board
      allowed a retrospective review of PET/CT images obtained in 78 patients with non
      head and neck cancer and waived the requirement for informed consent. The
      accumulation of FDG in 11 normal head and neck structures was visually and
      quantitatively assessed retrospectively. Positive rate percentage (PRP) was
      defined as the sum of the percentages of patients with grade 2 and grade 3 tracer
      uptake intensity. Standardized uptake values (SUVs) were calculated for
      quantitative analysis. Mean SUVs were compared between the male and female
      patients by using the unpaired t test, and the correlation between FDG uptake and
      patient age was assessed by using the Pearson correlation coefficient test.
      RESULTS: Intense tracer uptake was usually seen in the palatine tonsils (PRP,
      98%; mean SUV, 3.48), soft palate (PRP, 96%; mean SUV, 3.13), and lingual tonsils
      (PRP, 96%; mean SUV, 3.11). In the inferior concha (PRP, 4%; mean SUV, 1.56),
      thyroid gland (PRP, 3%; mean SUV, 1.31), and tongue (PRP, 1%; mean SUV, 1.39),
      uptake was typically minimal. FDG accumulation was variable in the sublingual
      glands (PRP, 72%; mean SUV, 2.93), spinal cord (PRP, 64%; mean SUV, 2.12),
      submandibular glands (PRP, 53%; mean SUV, 2.11), parotid glands (PRP, 51%; mean
      SUV, 1.90), and vocal cords (PRP, 19%; mean SUV, 1.77). The mean normal-tissue
      SUV in the soft palate was higher in male than in female patients (P <.01). A
      negative correlation between age and physiologic FDG uptake was seen in the
      palatine tonsils (r=-0.51, P <.001) and sublingual glands (r=-0.70, P <.001).
      CONCLUSION: Intense FDG uptake was usually observed in the palatine tonsils,
      lingual tonsils, and soft palate, whereas uptake in the major salivary glands was
      variable.

PMID- 15734939
TI  - Placement of peripherally inserted central catheters without fluoroscopy in
      children: initial catheter tip position.
AB  - PURPOSE: To determine how often placement of peripherally inserted central
      catheters (PICCs) without imaging guidance results in an initially correct
      central venous catheter tip location. MATERIALS AND METHODS: This study was
      approved by the hospital's institutional review board, which waived the
      requirement for informed consent. In a children's hospital, 843 PICCs were placed
      in 698 patients (age range, 0 days to 26 years; mean, 6.9 years) during a 14
      month study period. All PICCs were placed by a specialized team of PICC nurses
      and interventional radiology technologists in an angiography suite with the
      supervision of pediatric interventional radiologists. All catheters were threaded
      blindly to a previously estimated length by either a PICC nurse or a pediatric
      interventional radiologist, according to National Association of Vascular Access
      Networks guidelines, and the initial PICC tip location was then determined by
      means of spot fluoroscopy. PICC tips were regarded as central if they resided
      anywhere within the superior vena cava (SVC). All catheters were then manipulated
      with intermittent fluoroscopic guidance to achieve a final central position in
      the distal third of the SVC. A chi2 test was used to compare initial and final
      PICC tip locations according to patient age, catheter size, accessed vein, and
      need for radiologist assistance. A t test was used to compare procedure time with
      and without radiologist assistance. RESULTS: Analysis included 843 consecutively
      placed pediatric PICCs, of which 723 (85.8%) had a noncentral initial PICC tip
      position and required additional manipulation. After catheter repositioning
      performed with intermittent fluoroscopic guidance, a final central PICC tip
      location was achieved in 760 PICCs (90.2%). CONCLUSION: Pediatric PICC placement
      without fluoroscopic guidance required catheter manipulation of initial PICC tip
      position in 723 cases (85.8%). PICC placement with fluoroscopic guidance is
      highly successful, and the authors believe it is best performed in an angiography
      suite.

PMID- 15734940
TI  - The target sign: extremity.

PMID- 15734941
TI  - Three-dimensional venography of the brain with a volumetric interpolated
      sequence.
AB  - Informed consent was obtained from all patients before participation; study was
      approved by institutional review board. Three-dimensional (3D) gradient-echo
      magnetic resonance sequences can be optimized for rapid acquisition through
      asymmetric k-space sampling and interpolation of image data. A T1-weighted
      volumetric interpolated brain examination sequence (acquisition time, 1 minute 24
      seconds) was prospectively compared qualitatively and quantitatively with
      magnetization-prepared rapid acquisition gradient-echo sequence (acquisition
      time, 6 minutes 6 seconds) for venography of cerebral venous structures in 21
      female and seven male consecutive patients (mean age, 52.9 years; range, 16-81
      years). Although signal- and contrast-to-noise ratios were substantially lower
      for volumetric interpolated sequence, difference in the subjective quality of
      visualization of cerebral venous structures was not significant (P >.05).
      Volumetric interpolated brain examination seems promising as a more time
      efficient alternative for 3D imaging of cerebral venous structures.

PMID- 15734942
TI  - Human brain: reliability and reproducibility of pulsed arterial spin-labeling
      perfusion MR imaging.
AB  - The Committee of Human Research of the University of California San Francisco
      approved this study, and all volunteers provided written informed consent. The
      goal of this study was to prospectively determine the global and regional
      reliability and reproducibility of noninvasive brain perfusion measurements
      obtained with different pulsed arterial spin-labeling (ASL) magnetic resonance
      (MR) imaging methods and to determine the extent to which within-subject
      variability and random noise limit reliability and reproducibility. Thirteen
      healthy volunteers were examined twice within 2 hours. The pulsed ASL methods
      compared in this study differ mainly with regard to magnetization transfer and
      eddy current effects. There were two main results: (a) Pulsed ASL MR imaging
      consistently had high measurement reliability (intraclass correlation
      coefficients greater than 0.75) and reproducibility (coefficients of variation
      less than 8.5%), and (b) random noise rather than within-subject variability
      limited reliability and reproducibility. It was concluded that low signal-to
      noise ratios substantially limit the reliability and reproducibility of perfusion
      measurements.

PMID- 15734943
TI  - Telomerase activity predicts malignancy in percutaneous image-guided needle
      biopsy specimens of the abdomen and pelvis.
AB  - PURPOSE: To determine prospectively if assessment of telomerase activity in
      percutaneous needle biopsy specimens improves sensitivity and specificity in the
      diagnosis of abdominal and pelvic malignancy. MATERIALS AND METHODS: The study
      was approved by the institutional review board, and written informed consent was
      obtained from all patients. A prospective double-blinded design was used to
      assess telomerase activity in abdominal and pelvic biopsy specimens from 99
      patients (64 men, 35 women; age range, 22-87 years). After the clinical sample
      was retrieved, a study specimen from an extra needle pass was divided and
      independently analyzed for cytologic characteristics and telomerase activity. The
      final diagnosis was based on chart review at a minimum 1-year follow-up.
      Statistical analyses included sensitivity, specificity, and accuracy of cytologic
      examination and/or telomerase activity in predicting malignancy. RESULTS: Data
      from study specimens indicated that the sensitivity, specificity, and accuracy of
      telomerase activity (n=99) in predicting malignancy were 55%, 79%, and 60%,
      respectively. For cytologic examination (n=86), the sensitivity, specificity, and
      accuracy in predicting malignancy were 74%, 94%, and 78%, respectively. Combining
      the two tests (n=86) and classifying a positive reading with either test as
      malignant improved sensitivity (83%) (P <.05) without altering specificity (76%).
      In 20 patients who had clinical sample reports that were classified as
      indeterminate, telomerase activity (n=20) yielded a higher sensitivity (62%) (P
      <.05) and similar specificity (86%) compared with cytologic examination (n=15),
      which yielded a sensitivity of 11% and a specificity of 83%. CONCLUSION: In
      percutaneous biopsy specimens of the abdomen and pelvis, the combination of
      cytologic examination and telomerase activity yielded an increased sensitivity in
      predicting malignancy. In addition, assessing telomerase activity can help
      identify cancer even when cytologic results are indeterminate.

PMID- 15734944
TI  - Radiation risk of body CT: what to tell our patients and other questions.

PMID- 15734945
TI  - Patient radiation dose from vertebroplasty and kyphoplasty.

PMID- 15734946
TI  - Women with history of breast cancer excluded from screening programs: is it the
      right choice?

PMID- 15734949
TI  - The critical role of risk-benefit assessments in cancer prevention.

PMID- 15734947
TI  - Stunning with 131I diagnostic whole-body imaging of patients with thyroid cancer.

PMID- 15734950
TI  - Exploratory study of ovarian intraepithelial neoplasia.
AB  - PURPOSE: This was an exploratory study to test two hypotheses related to
      potential epithelial precursors to ovarian cancer: (a) histologically normal
      ovarian surface epithelium exhibited changes in the nuclear chromatin pattern,
      which indicate an ovarian abnormality, and (b) such changes were detectable in
      the ovarian surface epithelium of cancer-free subjects who were at high risk for
      ovarian cancer. EXPERIMENTAL DESIGN: Ovaries were carefully collected to avoid
      damage to the surface epithelium. Five-micron-thick histologic sections were cut
      and stained with H&E. High-resolution images were recorded from the ovarian
      surface epithelium and from the underlying stroma of ovaries from normal women
      (10 cases), women at high risk of developing ovarian cancer (7 cases), and
      histologically normal areas adjacent to ovarian cancer (3 cases). Karyometric
      features and measurements of nuclear abnormality were computed for 3,390
      epithelial nuclei. Discriminant function analyses and unsupervised learning
      algorithms were employed to define deviations from normal and to identify the
      subpopulations of nuclei exhibiting these changes. RESULTS: Epithelium from
      ovaries harboring a malignant lesion had changes in the nuclear chromatin pattern
      consistent with a second phenotype, which were not visually detected with
      histopathologic surveillance. This phenotype was also present in the ovaries
      obtained from women at increased risk of ovarian cancer, suggesting that it may
      represent a premalignant abnormality. These changes were statistically
      significant. CONCLUSION: The observed changes in karyometric features were
      sufficiently distinct to warrant further study as both diagnostic and prognostic
      biomarkers for early detection and prevention of ovarian cancer.

PMID- 15734951
TI  - Soluble epidermal growth factor receptor (sEGFR) [corrected] and cancer antigen
      125 (CA125) as screening and diagnostic tests for epithelial ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) is the leading cause of death among all
      gynecologic cancers in the United States. Because women who are diagnosed with
      early stage disease have a better prognosis than women diagnosed with late stage
      disease, early detection represents a potentially practical approach to reduce
      the mortality associated with EOC. Unfortunately, no single screening test has
      proven to be effective for this purpose, and a valid and feasible screening
      program to detect early stage EOC in the general population has not yet been
      devised. Consequently, research has focused on coupling two or more screening
      modalities to improve program validity and feasibility. Serum cancer antigen 125
      (CA125) and a soluble isoform of the epidermal growth factor receptor (p110
      sEGFR) have been studied individually as biomarkers of ovarian cancer. In this
      study, we compare serum CA125 levels and sEGFR concentrations in women with EOC
      to women with benign gynecologic conditions of ovarian and non-ovarian origin. We
      show that serum sEGFR concentrations are lower in patients with EOC than in women
      with benign gynecologic conditions, whereas serum CA125 levels are higher in
      patients to EOC compared with women with benign gynecologic conditions. These
      data also reveal that age and serum sEGFR concentrations modify the association
      between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and
      sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern
      EOC patients from women with benign ovarian tumors and non-ovarian gynecologic
      conditions. Our analyses show that parallel testing with fixed sEGFR and CA125
      cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing
      with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity,
      and overall accuracy to discern patients with EOC from women with benign ovarian
      and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and
      CA125, thus, has improved utility for screening and diagnosing EOC, which may
      increase the positive predictive value of a multimodal screening program that
      incorporates these biomarkers to detect and subsequently differentiate benign
      from malignant ovarian tumors.

PMID- 15734952
TI  - Double-strand break repair gene polymorphisms and risk of breast or ovarian
      cancer.
AB  - Deficiencies in DNA repair have been hypothesized to increase cancer risk and
      excess cancer incidence is a feature of inherited diseases caused by defects in
      DNA damage recognition and repair. We investigated, using a case-control design,
      whether the double-strand break repair gene polymorphisms RAD51 5' untranslated
      region -135 G > C, XRCC2 R188H G > A, and XRCC3 T241M C > T were associated with
      risk of breast or ovarian cancer in Australian women. Sample sets included 1,456
      breast cancer cases and 793 age-matched controls ages under 60 years of age, 549
      incident ovarian cancer cases, and 335 controls of similar age distribution. For
      the total sample and the subsample of Caucasian women, there were no significant
      differences in genotype distribution between breast cancer cases and controls or
      between ovarian cancer cases and combined control groups. The crude odds ratios
      (OR) and 95% confidence intervals (95% CI) associated with the RAD51 GC/CC
      genotype frequency was OR, 1.10; 95% CI, 0.80-1.41 for breast cancer and OR,
      1.22; 95% CI, 0.92-1.62 for ovarian cancer. Similarly, there were no increased
      risks associated with the XRCC2 GA/AA genotype (OR, 0.98; 95% CI, 0.76-1.26 for
      breast cancer and OR, 0.93; 95% CI, 0.69-1.25 for ovarian cancer) or the XRCC3
      CT/TT genotype (OR, 0.92; 95% CI, 0.77-1.10 for breast cancer and OR, 0.87; 95%
      CI, 0.71-1.08 for ovarian cancer). Results were little changed after adjustment
      for age and other measured risk factors. Although there was little statistical
      power to detect modest increases in risk for the homozygote variant genotypes,
      particularly for the rare RAD51 and XRCC2 variants, the data suggest that none of
      these variants play a major role in the etiology of breast or ovarian cancer.

PMID- 15734953
TI  - Nipple aspirate fluid cytology and the Gail model for breast cancer risk
      assessment in a screening population.
AB  - BACKGROUND: Recent guidelines suggest that chemoprevention with tamoxifen may be
      appropriate for women who have a 5-year risk of breast cancer greater than 1.66%
      calculated using the Gail model. OBJECTIVES: To determine whether nipple aspirate
      fluid (NAF) cytology combined with the Gail model provides breast cancer risk
      assessment that is superior to either method alone. METHODS: Prospective
      observational cohort of 6,904 asymptomatic women. Breast cancer cases were
      identified through follow-up with the women and linkage to cancer registries. We
      used proportional hazards modeling to recalculate the coefficients for the
      predictor variables used in the Gail model. NAF cytology was added to create a
      second model. The two models were compared using the concordance statistic (c
      statistic). RESULTS: During 14.6 years of follow-up, 400 women were diagnosed
      with breast cancer. There were 940 (14%) women with hyperplasia and 109 (1.6%)
      women with atypical hyperplasia found in NAF. Adding NAF cytology results to the
      Gail model significantly improved the model fit (P < 0.0001). The c-statistic for
      the Gail model was 0.62, indicating only modest discriminatory accuracy. Adding
      NAF cytology to the model increased the c-statistic to 0.64. NAF cytology results
      had the largest effect on discriminatory accuracy among women in the upper third
      of Gail model risk. The relative incidence for the highest quintile of risk score
      compared with the lowest quintile was 7.2 for the Gail model and 8.0 for the
      model including NAF cytology. CONCLUSION: NAF cytology has the potential to
      improve prediction models of breast cancer incidence, particularly for high-risk
      women.

PMID- 15734954
TI  - Cytochrome P450 1B1 and catechol-O-methyltransferase genetic polymorphisms and
      breast cancer risk in Chinese women: results from the shanghai breast cancer
      study and a meta-analysis.
AB  - Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are
      important estrogen-metabolizing enzymes and, thus, genetic polymorphisms of these
      enzymes may affect breast cancer risk. A population-based case-control study was
      conducted to assess the association of breast cancer risk with CYP1B1 and COMT
      polymorphisms. A meta-analysis was done to summarize the findings from this and
      previous studies. Included in this study were 1,135 incident breast cancer cases
      diagnosed from August 1996 through March 1998 among female residents of Shanghai
      and 1,235 randomly selected, age frequency-matched controls from the same general
      population. The common alleles of the CYP1B1 gene were Arg (79.97%) in codon 48,
      Ala (80.53%) in codon 119, and Leu (86.57%) in codon 432. The Val allele
      accounted for 72.46% of the total alleles identified in codon 108/158 of the COMT
      gene. No overall associations of breast cancer risk were found with any of the
      single nucleotide polymorphisms described above. This finding was supported by a
      meta-analysis of all previous published studies. No gene-gene interactions were
      observed between CYP1B1 and COMT genotypes. The associations of breast cancer
      risk with factors related to endogenous estrogen exposure, such as years of
      menstruation and body mass index, were not significantly modified by the CYP1B1
      and COMT genotypes. We observed, however, that women who carried one copy of the
      variant allele in CYP1B1 codons 48 or 119 were less likely to have estrogen
      receptor-positive breast cancer than those who carried two copies of the
      corresponding wild-type alleles. The results from this study were consistent with
      those from most previous studies, indicating no major associations of breast
      cancer risk with CYP1B1 and COMT polymorphisms.

PMID- 15734955
TI  - Polymorphisms in XRCC1 modify the association between polycyclic aromatic
      hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and breast
      cancer risk.
AB  - The variability in DNA repair capacity of the general population may depend in
      part upon common variants in DNA repair genes. X-ray repair cross complementing
      group 1 (XRCC1) is an important DNA base excision repair gene and exhibits
      polymorphic variation. Using the Long Island Breast Cancer Study Project, a
      population-based case-control study, we evaluated the hypothesis that two common
      single nucleotide polymorphisms of XRCC1 (codon 194 Arg-->Trp and 399 Arg-->Gln)
      influence breast cancer susceptibility and interact with polycyclic aromatic
      hydrocarbon (PAH)-DNA adducts, cigarette smoking, and intake of fruits and
      vegetables and antioxidants. The available sample for genotyping included 1,067
      cases and 1,110 controls. Genotyping was done by a high-throughput single
      nucleotide extension assay with fluorescence polarization detection of the
      incorporated nucleotide. We observed no significant increases in risk among all
      subjects who were carriers of XRCC1 194Trp or 399Gln alleles. Among never
      smokers, we observed an increased risk of breast cancer in 399Gln carriers [odds
      ratio (OR), 1.3; 95% confidence interval (CI), 1.0-1.7). Further analysis
      indicated a suggestive weak additive interaction between the 399Gln allele and
      detectable PAH-DNA adducts (OR for exposure with mutant genotype, 1.9; 95% CI,
      1.2-3.1). The estimated age-adjusted interaction contrast ratio (ICR) and 95% CI
      (ICR, 0.38; 95% CI, -0.32 to 1.10) indicated that the departure from additivity
      was not statistically significant, but that there was some suggestion of a
      relative excess risk due to the interaction. In subjects with at least one copy
      of XRCC1 194Trp allele, there was a moderate interaction with high intake of
      fruits and vegetables (>/=35 half-cup servings per week of any fruits, fruit
      juices, and vegetables, OR, 0.58; 95% CI, 0.38-0.89; ICR, -0.49; 95% CI, -0.03 to
      -0.95), and dietary plus supplement antioxidant intake with 33% to 42% decreases
      in breast cancer risk compared with those with the Arg194Arg genotype and low
      intake individuals. These results do not show that the two genetic polymorphisms
      of XRCC1 independently influence breast cancer risk. However, there is evidence
      for interactions between the two XRCC1 single nucleotide polymorphisms and PAH
      DNA adducts or fruit and vegetable and antioxidant intake on breast cancer risk.
      Further understanding of the biological function of XRCC1 variants and their
      interactions with PAH-DNA adducts, antioxidants, and other genes in the pathway
      are needed.

PMID- 15734956
TI  - The association of measured breast tissue characteristics with mammographic
      density and other risk factors for breast cancer.
AB  - BACKGROUND: We have examined the relationships between the measured properties of
      breast tissue and mammographic density and other risk factors for breast cancer,
      using breast tissue obtained at forensic autopsy and not selected for the
      presence of abnormalities. METHODS: We used randomly selected tissue blocks taken
      from breast tissue slices obtained by s.c. mastectomy at the time of forensic
      autopsy to measure histologic features using quantitative microscopy. The
      proportions of the biopsy occupied by cells (estimated by nuclear area),
      glandular structures, and collagen were determined. These measurements were
      examined in relation to the percent density in the faxitron image of the tissue
      slice from which the biopsy was taken and other risk factors for breast cancer.
      RESULTS: The percent mammographic density was associated with the proportion of
      the area of the biopsy occupied by nuclei, both epithelial and nonepithelial, and
      by collagen and the area of glandular structures. Several other risk factors for
      breast cancer, notably body weight, parity, and number of births, and menopausal
      status, that are associated with variations in mammographic density, were also
      associated with differences in one or more of these tissue features. CONCLUSION:
      All risk factors for breast cancer must ultimately exert their influence by an
      effect on the breast, and these findings suggest that, for some risk factors,
      this influence includes an effect on the number of cells and the quantity of
      collagen.

PMID- 15734957
TI  - Oral contraceptive use and risk of early-onset breast cancer in carriers and
      noncarriers of BRCA1 and BRCA2 mutations.
AB  - BACKGROUND: Recent oral contraceptive use has been associated with a small
      increase in breast cancer risk and a substantial decrease in ovarian cancer risk.
      The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are
      unclear. METHODS: Subjects were population-based samples of Caucasian women that
      comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40
      (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San
      Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney,
      Australia. Relative risks by carrier status were estimated using unconditional
      logistic regression, comparing oral contraceptive use in case groups defined by
      mutation status with that in controls. RESULTS: After adjustment for potential
      confounders, oral contraceptive use for at least 12 months was associated with
      decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22;
      95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation
      carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69
      1.24). First use during or before 1975 was associated with increased risk for
      noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001).
      CONCLUSIONS: There was no evidence that use of current low-dose oral
      contraceptive formulations increases risk of early-onset breast cancer for
      mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers.
      Because current formulations of oral contraceptives may reduce, or at least not
      exacerbate, ovarian cancer risk for mutation carriers, they should not be
      contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.

PMID- 15734958
TI  - Genetic factors in catechol estrogen metabolism in relation to the risk of
      endometrial cancer.
AB  - 2-Hydroxylated metabolites of estrogen have been shown to have antiangiogenic
      effects and inhibit tumor cell proliferation, whereas 4-hydroxylated metabolites
      have been implicated in carcinogenesis. We examined whether polymorphisms in
      certain genes involved in estrogen metabolism are associated with endometrial
      cancer risk in a population-based case-control study with 371 cases and 420
      controls. Based on previously published genotype-phenotype correlation studies,
      we defined variant alleles thought to increase estrogen 2-hydroxylation as
      presumptively low-risk (CYP1A1 m1 T6235C and m2 Ile(462)Val) and those thought to
      increase estrogen 4-hydroxylation as high-risk (CYP1A1 m4 Thr(461)Asn, CYP1A2
      A734C, and CYP1B1 Leu(432)Val). Odds ratios (OR) and 95% confidence intervals
      (95% CI) were calculated using unconditional logistic regression. Carrying at
      least one CYP1A1 m1 or m2 variant allele was associated with a decreased risk of
      endometrial cancer [ORs (95% CIs), 0.64 (0.44-0.93) and 0.54 (0.30-0.99),
      respectively]. No strong alteration in risk was observed among women with any of
      the putative high-risk alleles. When CYP1A1, CYP1A2, and CYP1B1 genotypes were
      combined and ranked by the number of putative low-risk genotypes carried, women
      with four or five low-risk genotypes had a reduced risk of endometrial cancer
      (OR, 0.29; 95% CI, 0.15-0.56) compared with women with one or none. No
      appreciable alteration in risk was observed among women carrying two or three low
      risk genotypes. Some of our findings are consistent with the hypothesis that
      increased estrogen 2-hydroxylation is associated with decreased endometrial
      cancer risk, but replication of these results is required before any firm
      conclusions can be reached.

PMID- 15734959
TI  - Comparison of human papillomavirus messenger RNA and DNA detection: a cross
      sectional study of 4,136 women >30 years of age with a 2-year follow-up of high
      grade squamous intraepithelial lesion.
AB  - The purpose of this study was to compare the detection of human papillomavirus
      (HPV) DNA with detection of mRNA. The study included 4,136 women >30 years of
      age. E6/E7 mRNA expression from the carcinogenic HPV types 16, 18, 31, 33, and 45
      was detected by the PreTect HPV-Proofer assay, whereas the presence of HPV DNA
      was detected by Gp5+/6+ consensus PCR followed by type-specific PCR. A total of
      4.0% had an abnormal cytologic diagnosis, 3.0% were positive by PreTect HPV
      Proofer, 4.4% by type-specific PCR, and 10.4% by consensus PCR. For detection of
      HPV in high-grade squamous intraepithelial lesion (HSIL), no significant
      difference was observed between PreTect HPV-Proofer and consensus PCR. For women
      with a cytologic normal, atypical squamous cell of uncertain significance, and
      low-grade SIL diagnosis, the detection rate of HPV was significantly higher by
      Gp5+/6+ consensus PCR (P < 0.005) than by PreTect HPV-Proofer. Histology
      confirmed 14 of 23 cytologic HSIL as cervical intraepithelial neoplasia grade >2.
      Of these women, PreTect HPV-Proofer and type-specific PCR detected 12, whereas
      consensus PCR detected 13. In conclusion, for HSIL, detection of E6/E7
      transcripts from HPV types 16, 18, 31, 33, and 45 are present to the same degree
      as DNA detected by consensus PCR. Equally important, only a small proportion of
      the HPV DNA-positive women with a normal, atypical squamous cell of uncertain
      significance or low-grade SIL diagnosis had a detectable mRNA expression. HPV
      E6/E7 mRNA detection by PreTect HPV-Proofer represents a new promising test as an
      adjunct to cytology.

PMID- 15734960
TI  - Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA
      repair enzymes in a population with aflatoxin exposure and hepatitis B virus
      endemicity.
AB  - High rates of hepatocellular carcinoma (HCC) in The Gambia, West Africa, are
      primarily due to a high prevalence of chronic hepatitis B virus infection and
      heavy aflatoxin exposure via groundnut consumption. We investigated genetic
      polymorphisms in carcinogen-metabolizing (GSTM1, GSTT1, HYL1*2) and DNA repair
      (XRCC1) enzymes in a hospital-based case-control study. Incident HCC cases (n =
      216) were compared with frequency-matched controls (n = 408) with no clinically
      apparent liver disease. Although the prevalence of variant genotypes was
      generally low, in multivariable analysis (adjusting for demographic factors,
      hepatitis B virus, hepatitis C virus, and TP53 status), the GSTM1-null genotype
      [odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.21-4.95] and the
      heterozygote XRCC1-399 AG genotype (OR, 3.18; 95% CI, 1.35-7.51) were
      significantly associated with HCC. A weak association of the HYL1*2 polymorphism
      with HCC was observed but did not reach statistical significance. GSTT1 was not
      associated with HCC. The risk for HCC with null GSTM1 was most prominent among
      those with the highest groundnut consumption (OR, 4.67; 95% CI, 1.45-15.1) and
      was not evident among those with less than the mean groundnut intake (OR, 0.64;
      95% CI, 0.20-2.02). Among participants who had all three suspected aflatoxin
      related high-risk genotypes [GSTM1 null, HLY1*2 (HY/HH), and XRCC1 (AG/GG)], a
      significant 15-fold increased risk of HCC was observed albeit with imprecise
      estimates (OR, 14.7; 95% CI, 1.27-169). Our findings suggest that genetic
      modulation of carcinogen metabolism and DNA repair can alter susceptibility to
      HCC and that these effects may be modified by environmental factors.

PMID- 15734961
TI  - Hepatitis B 1762T/1764A mutations, hepatitis C infection, and codon 249 p53
      mutations in hepatocellular carcinomas from Thailand.
AB  - Hepatocellular carcinoma is one of the leading causes of cancer death worldwide.
      The etiology of liver cancer is multifactorial, and infection with hepatitis B
      virus (HBV), whose pathogenesis is exacerbated by the acquisition of mutations
      that accelerate carcinogenesis, or hepatitis C virus (HCV) and dietary exposure
      to aflatoxin B(1) all contribute to elevating one's risk for this disease. In
      this study, we sought to determine the contributions of these agents by measuring
      the occurrence of an HBV 1762(T)/1764(A) double mutation, an aflatoxin-specific
      249(G-->T) mutation of the p53 gene, and HCV in plasma of 34 HCC cases and 68 age
      and gender-matched controls, and in 25 liver tumors from northern Thailand. In
      total, 14 cases, 5 controls, and 19 tumors had detectable levels of HBV DNA. All
      14 cases, 2 controls (2.9%), and 17 tumors (89.5%) were positive for the HBV
      double mutation. Nine cases (26.5%), 10 controls (14.7%), and 6 tumors (24%) were
      positive for the p53 mutation. Five cases (14.7%), no controls, and 4 tumors
      (16%) had both mutations. The median age of HCC diagnosis in these 5 cases was 34
      years versus 51 years for other cases. Five cases (14.7%) and 1 control (1.5%)
      were HCV enzyme immunoassay positive. Thus, specific HBV, HCV, and aflatoxin
      biomarkers reveal the complexity of risks contributing to HCC in northern
      Thailand and suggest further application of these biomarkers as intermediate end
      points in prevention, intervention trials, and etiologic investigations.

PMID- 15734962
TI  - Chlamydial antibodies and risk of prostate cancer.
AB  - OBJECTIVE: We assessed the risk of prostate cancer by exposure to Chlamydia
      trachomatis. METHOD: Seven hundred thirty eight cases of prostate cancer and
      2,271 matched controls were identified from three serum sample banks in Finland,
      Norway, and Sweden by linkage to the population based cancer registries. RESULTS:
      A statistically significant inverse association (odds ratio, 0.69; 95% confidence
      interval, 0.51-0.94) was found. It was consistent by different serotypes and
      there was a consistent dose-response relationship. CONCLUSION: C. trachomatis
      infection is not likely to increase the risk of prostate cancer. Whether the
      inverse relationship is true or due to difficulties in measuring the true
      exposure in prostatic tissue by serology, confounders or other sources of error
      remain open.

PMID- 15734963
TI  - Nonsteroidal anti-inflammatory drugs and risk of prostate cancer in the Baltimore
      Longitudinal Study of Aging.
AB  - BACKGROUND: Laboratory and epidemiologic studies suggest that aspirin and
      nonaspirin nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk of
      cancer, possibly via inhibition of the cyclooxygenase enzymes. We evaluated the
      association of aspirin and nonaspirin NSAIDs with subsequent prostate cancer in a
      prospective study. We also assessed whether use of these drugs influences serum
      prostate-specific antigen (PSA) concentration. METHODS: Participants were 1,244
      male members of the Baltimore Longitudinal Study of Aging. Use of prescription
      and over-the-counter drugs was collected by questionnaire and interview at
      multiple study visits. One hundred forty-one prostate cancer cases diagnosed
      between 1980 and May 2004 were confirmed by medical record review. We used Cox
      proportional hazards regression to estimate the rate ratio (RR) of prostate
      cancer updating drug use over time and taking into account age and year. We used
      generalized estimating equations to calculate age-adjusted geometric mean PSA
      concentration by aspirin or nonaspirin NSAIDs use among 933 of the men without
      prostate cancer, for whom 3,749 PSA measurements in archived sera had been done
      previously. RESULTS: On 46.0% and 21.5% of the visits, current use of aspirin or
      nonaspirin NSAIDs (mostly ibuprofen) was reported, respectively. The RRs of
      prostate cancer comparing ever to never use were 0.76 [95% confidence interval
      (95% CI), 0.54-1.07] for aspirin, 0.79 (95% CI, 0.54-1.16) for nonaspirin NSAIDs,
      and 0.71 (95% CI, 0.49-1.02) for either medication. The association for ever use
      of either aspirin or nonaspirin NSAIDs was suggestively more pronounced in men
      <70 years (RR, 0.54; 95% CI, 0.27-1.03) than in men >/=70 years (RR, 0.78; 95%
      CI, 0.50-1.22; P(interaction) = 0.73). The RR for current use of either drug was
      attenuated relative to ever use. Mean PSA concentration did not differ between
      users and nonusers of either aspirin or nonaspirin NSAIDs (1.01 versus 0.98
      ng/mL, P = 0.56). CONCLUSION: In this prospective study, men, in particular
      younger men, who had ever used aspirin or nonaspirin NSAIDs had a modest
      nonstatistically significant lower risk of prostate cancer. The modest inverse
      association was unlikely due to detection bias that might have resulted if anti
      inflammatory drugs had influenced serum PSA concentration.

PMID- 15734964
TI  - Macrophage scavenger receptor 1 999C>T (R293X) mutation and risk of prostate
      cancer.
AB  - BACKGROUND: Variants in the gene encoding the macrophage scavenger receptor 1
      (MSR1(4)) protein have been identified in men with prostate cancer, and several
      small studies have suggested that the 999C>T (R293X) protein-truncating mutation
      may be associated with an increased risk for this disease. METHODS: Using large
      case-control, cohort, and prostate cancer family studies conducted in several
      Western countries, we tested for the 999C>T mutation in 2,943 men with invasive
      prostate carcinoma, including 401 males from multiple-case families, 1,982 cases
      unselected for age, and 575 men diagnosed before the age of 56 years, and in
      2,870 male controls. Risk ratios were estimated by unconditional logistic
      regression adjusting for country and by a modified segregation analysis. A meta
      analysis was conducted pooling our data with published data. RESULTS: The
      prevalence of MSR1*999C>T mutation carriers was 0.027 (SE, 0.003) in cases and
      0.022 (SE, 0.002) in controls, and did not differ by country, ethnicity, or
      source. The adjusted risk ratio for prostate cancer associated with being a
      999C>T carrier was 1.31 [95% confidence interval (CI), 0.93-1.84; P = 0.16]. The
      modified segregation analysis estimated the risk ratio to be 1.20 (95% CI, 0.87
      1.66; P = 0.16). The risk ratio estimated from the meta-analysis was 1.34 (95%
      CI, 0.94-1.89; P = 0.10). CONCLUSION: Our large-scale analysis of case and
      controls from several countries found no evidence that the 999C>T mutation is
      associated with increased risk of prostate cancer. The meta-analysis suggests it
      is unlikely that this mutation confers more than a 2-fold increased risk.

PMID- 15734965
TI  - IGF1 (CA)19 repeat and IGFBP3 -202 A/C genotypes and the risk of prostate cancer
      in Black and White men.
AB  - We investigated the relationship between the insulin-like growth factor-1 (IGF1)
      cytosine-adenine repeat (CA)(19) polymorphism located upstream of the gene's
      transcription start site, the insulin-like growth factor binding protein-3
      (IGFBP3) -202 A/C promoter region polymorphism, and prostate cancer risk in Black
      and White men. Study subjects were U.S. veterans ages 41 to 75 years identified
      at the Durham Veterans Administration Medical Center over a 2.5-year period.
      Controls (n = 93) were frequency matched to cases (n = 100) based on race (Black
      or White) and age. Multivariable unconditional logistic regression was used to
      calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations
      between the polymorphisms and prostate cancer risk. For Blacks and Whites
      combined, an inverse association between prostate cancer and being homozygous for
      the most common IGF1 repeat allele, (CA)(19), (adjusted OR, 0.3; 95% CI, 0.1-0.7)
      was observed. Similar associations were noted for both Blacks (OR, 0.2; 95% CI,
      0.0-0.8) and Whites (OR, 0.4; 95% CI, 0.1-1.6) separately. No statistically
      significant associations between the IGFBP3 C allele and prostate cancer were
      noted for Blacks (adjusted OR, 2.3; 95% CI, 0.8-6.2) or Whites (OR, 1.0; 95% CI,
      0.3-3.1). The prevalence of the homozygous IGF1 (CA)(19) genotype was much lower
      in Black controls (21%) than White controls (46%), which may, in part, explain
      the increased prostate cancer incidence in Black versus White men. Further
      research is needed to confirm these findings.

PMID- 15734967
TI  - Surveillance patterns and polyp recurrence following diagnosis and excision of
      colorectal polyps in a medicare population.
AB  - OBJECTIVE: Study objectives were to determine surveillance and polyp recurrence
      rates among older, increased-risk patients who have been diagnosed and excised of
      colorectal polyps. The high incidence of colorectal cancers in the Medicare
      eligible population, the strong evidence linking reductions in mortality from
      colorectal cancer by removal of colorectal polyps, and the paucity of
      postpolypectomy surveillance data in this population all supported the need for
      this study. METHODS: This retrospective study used Medicare claims data to
      identify a cohort of 19,895 beneficiaries ages >/=65 years diagnosed and excised
      of colorectal polyps in 1994. Survival analysis was used to compute surveillance
      and polyp recurrence rates over 5 years. Log-rank test was used for all
      statistical comparisons. RESULTS: Median time to first surveillance was 2.6
      years. Surveillance rates for 1, 3, and 5 years were 17.6%, 55.8%, and 74.5%,
      respectively. Twenty-six percent had no surveillance event. Polyp recurrence
      rates for 1, 3, and 5 years were 10.9%, 38.2%, and 52.6%, respectively. Males and
      younger patients were more likely to undergo surveillance and showed higher polyp
      recurrence rates. CONCLUSIONS: The high likelihood of polyp recurrence
      underscores the need for continued efforts to promote awareness of and compliance
      with postpolypectomy surveillance. Efforts to increase surveillance rates among
      individuals diagnosed with colorectal polyps and making available additional
      treatment options that may prevent the recurrence of polyps and/or their possible
      progression to colorectal cancer should help make significant progress in
      reaching the Healthy People 2010 goal of reducing colorectal cancer deaths by 34%
      by the year 2010.

PMID- 15734966
TI  - Use of colonoscopy for colorectal cancer screening: evidence from the 2000
      National Health Interview Survey.
AB  - BACKGROUND: The use of colonoscopy as a primary screening tool for colorectal
      cancer is gaining momentum owing to several studies suggesting superior
      effectiveness and the recent, favorable decision by Medicare to cover all routine
      screening colonoscopies. This study documents the use of colonoscopy versus other
      tests to screen for colorectal cancer. MATERIALS AND METHODS: Data from the 2000
      National Health Interview Survey were analyzed. Fecal occult blood test (FOBT),
      sigmoidoscopy, and colonoscopy done for any reason and for routine screening only
      were analyzed for those >/=50 years without previously diagnosed colorectal
      cancer (n = 12,505). RESULTS: The proportion of the total eligible population
      receiving any of the recommended tests for all possible reasons and for screening
      purposes only is 34.6% and 25.1%, respectively. For routine screening purposes,
      the test most commonly utilized was FOBT (55.6%) followed by colonoscopy (29.1%)
      and sigmoidoscopy (15.3%). When usage was assessed for all reasons, FOBT was
      still most commonly utilized (45.8%) followed by colonoscopy (38.7%) and
      sigmoidoscopy (15.5%). The elderly, non-White males and those with private
      insurance have a higher probability of receiving colonoscopy than FOBT. Several
      regional differences exist, including higher probability of undergoing
      sigmoidoscopy versus colonoscopy in the West. CONCLUSIONS: Only one fourth (upper
      limit one third) of the study population complied with colorectal cancer
      screening recommendations. Nearly one third of the routine screening tests done
      in 2000 were colonoscopies. This study provides baseline values that can be used
      to project future colonoscopy demand and identify potential supply barriers.

PMID- 15734968
TI  - A simulation model for colorectal cancer screening: potential of stool tests with
      various performance characteristics compared with screening colonoscopy.
AB  - OBJECTIVE: Many new stool tests intended to detect neoplastic cells or cell
      products are developed at present for colorectal cancer (CRC) screening. The aim
      of this study was to simulate a population-based screening setting to assess and
      compare the potential for early detection and prevention of CRC of screening
      based on stool tests with different sensitivity and specificity and of screening
      with colonoscopy as a primary screening tool. METHOD: A Markov model was
      developed aimed to estimate the proportion of CRC cases which are early detected
      or prevented due to screening as well as the number of equired stool tests and
      colonoscopies per early detected or prevented CRC case. Model outcomes were
      calculated for the offer of annual stool testing from age 55 to 74 in combination
      with colonoscopic follow-up of positive test results and for the offer of
      screening colonoscopy as a primary screening tool at ages 55 and 65. The long
      lasting risk reduction of colonoscopy allowing the removal of precancerous
      lesions was taken into account quantitatively. RESULTS: For a variety of stool
      tests with different performance characteristics, the proportion of CRC cases
      early detected or prevented was estimated to be higher for stool testing in
      combination with colonoscopic follow-up of positive test results compared with
      screening colonoscopy assuming levels of compliance to be expected for the
      respective screening scheme. Optimizing performance characteristics of stool
      tests in terms of detecting precancerous lesions, in addition to those in terms
      of detecting CRC, seemed to be crucial for maximizing effectiveness of CRC
      screening with stool tests. CONCLUSION: Screening based on new stool tests with
      colonoscopic follow-up of positive test results might offer a high potential for
      early detection or prevention of CRC.

PMID- 15734969
TI  - Diet, lifestyle, and genomic instability in the North Carolina Colon Cancer
      Study.
AB  - OBJECTIVE: Microsatellite instability (MSI) is one form of genomic instability
      that occurs in 10% to 20% of sporadic colon tumors and almost all hereditary
      nonpolyposis colon cancers. However, little is known about how environmental
      factors (e.g., diet) may influence MSI in sporadic colon cancer. METHODS: We used
      data from a population-based case-control study in North Carolina (486 colon
      cancer cases and 1,048 controls) to examine associations of diet (total energy,
      macronutrients, micronutrients, and food groups) with MSI. In-person interviews
      elicited information on potential colon cancer risk factors, and a previously
      validated food frequency questionnaire adapted to include regional foods was used
      to assess diet over the year before diagnosis or interview date. MSI was
      classified as MSI-high (MSI-H) and MSI-low or microsatellite stable (MSI-L/MSS).
      Multivariate logistic regression models estimated energy-adjusted and non-energy
      adjusted odds ratios (OR). RESULTS: Ten percent of the cases (n = 49) had MSI-H
      tumors (29% African American). The strongest associations between diet and MSI
      were observed in case-control comparisons: there was a robust inverse association
      between MSI-H status and beta-carotene [OR, 0.4; 95% confidence interval (95%
      CI), 0.2-0.9] and positive associations with energy-adjusted refined
      carbohydrates (OR, 2.2; 95% CI, 0.9-5.4) and non-energy-adjusted read meat intake
      (OR, 2.0; 95% CI, 0.9-4.2). Compared with controls, MSI-L/MSS tumors were
      statistically significantly associated with energy-adjusted vitamin C, vitamin E,
      calcium, dietary fiber, and dark green vegetables and positively associated with
      total energy intake (all Ps for trend < 0.05). In case-case comparisons, no
      dietary factors were significantly differently related to MSI-H compared with MSI
      L/MSS tumors. CONCLUSION: Refined carbohydrate and red meat consumption may
      promote development of MSI-H tumors, whereas beta-carotene may be associated with
      lower risk.

PMID- 15734970
TI  - Clinicopathologic correlation of up-regulated genes identified using cDNA
      microarray and real-time reverse transcription-PCR in human colorectal cancer.
AB  - PURPOSE: We hypothesize that changes in the transcription of up-regulated genes
      are biologically meaningful and may be linked to variations in tumor behavior and
      clinical features. This study aimed to find individual up-regulated genes
      responsible for clinicopathologic variations in human colorectal cancer.
      EXPERIMENTAL DESIGN: Genes up-regulated concurrently in four microarray
      experiments were taken as candidate genes; 20 candidate genes were verified using
      real-time reverse transcription-PCR in these four experiments, along with 27 new
      samples. The presence or absence of up-regulation of these genes was correlated
      with 10 clinicopathologic variables from 31 patients. The mRNA transcript levels
      of these 20 candidate genes in the 31 paired samples were also correlated with
      each other to disclose any expression relationship. RESULTS: Forty percent (8/20)
      of the candidate genes were verified by real-time reverse transcription-PCR to
      have a tumor/normal expression ratio > 2. Up-regulation of THY1 and PHLAD1 was
      associated with the presence of anemia in colon cancer patients (P = 0.036 and
      0.009, respectively). Up-regulation of HNRPA1 was more significant in cancer
      growing in the right-sided colon than the left side (P = 0.027). Up-regulated
      GPX2 was related to a higher degree of tumor differentiation (P = 0.019). c-MYC
      was significantly over-expressed in specimens from male compared with female
      colon cancer patients (P = 0.012). GRO1 was significantly up-regulated in
      patients younger than 65 years old (P = 0.010) and was found to be frequently
      over-expressed when cancers were less invasive. In addition, we found that
      normalized transcript levels of HNRPA1 were tightly associated with that of c-MYC
      (r = 0.948). CONCLUSIONS: Validation of microarray data using another independent
      laboratory approach is mandatory and statistical correlation between gene
      expression status and the patient's clinical features may reveal individual genes
      relevant to tumor behavior and clinicopathologic variations in human colorectal
      cancer.

PMID- 15734971
TI  - Nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer.
AB  - INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAID) might reduce risks of
      esophageal and gastric cancer, but previous studies are limited and provide
      somewhat conflicting results. METHODS: We tested these associations in a
      prospective, nested case-control study based on the General Practitioners
      Research Database, including over 2 million persons in the United Kingdom between
      1994 and 2001. In multivariate analyses we calculated odds ratios (OR) with 95%
      confidence intervals (95% CI). Data were stratified by history of upper
      gastrointestinal (UGI) disorders and recalculated using 2 years lag time on data
      (i.e., excluding all information 2 years before index date). RESULTS: Among
      4,340,207 person-years of follow-up, we identified 909 patients with esophageal
      cancer and 1,023 patients with gastric cancer. We randomly selected 10,000
      control subjects. Overall analysis suggested that long-term users of nonaspirin
      NSAIDs were at reduced risks of esophageal (OR, 0.82; 95% CI, 0.57-1.18) and
      gastric cancer (OR, 0.65; 95% CI, 0.44-0.94), whereas long-term aspirin users
      might be at decreased risk of esophageal cancer (OR, 0.76; 95% CI, 0.53-1.08),
      but not of gastric cancer (OR, 1.09; 95% CI, 0.82-1.45). All estimates of reduced
      risk were weakened in the 2 years lag time analysis except the association
      between nonaspirin NSAIDs long-term users and gastric cancer. Potentially
      protective effects were suggestive of being more marked among subjects with a
      history of UGI disorders. CONCLUSIONS: Nonaspirin NSAIDs long-term use was
      associated with a reduced risk of gastric cancer, whereas no other studied
      associations could be firmly established. Our results suggest that UGI disorders
      could distort the associations, although we could not show this with statistical
      significance. If such bias was to be true, the previously reported inverse
      associations might, at least partly, be explained by lack of appropriate
      adjustment for such disorders.

PMID- 15734972
TI  - Genetic polymorphisms of CYP2E1, GSTT1, GSTP1, GSTM1, ALDH2, and ODC and the risk
      of advanced precancerous gastric lesions in a Chinese population.
AB  - There have been few studies of the associations of genetic polymorphisms with
      precancerous gastric lesions. We conducted a cross-sectional study to compare the
      prevalences of several genetic polymorphisms in 302 subjects with mild chronic
      atrophic gastritis with prevalences in 606 subjects with deep intestinal
      metaplasia or dysplasia. This stratified random sample of 908 subjects was
      selected and analyzed for genetic polymorphisms from 2,628 individuals who had
      gastric biopsies with histopathology in 1989 in Linqu County, Shandong Province,
      China. In subjects with mild chronic atrophic gastritis, the frequencies of the
      variant (less common) alleles of CYP2E1 RsaI, CYP2E1 DraI, GSTP1, ALDH2, and ODC
      were, respectively, 0.156, 0.201, 0.189, 0.190, and 0.428. The frequencies of the
      null genotypes of GSTM1 and GSTT1 in the mild chronic atrophic gastritis group
      were 0.509 and 0.565, respectively. Comparing mild chronic atrophic gastritis
      with deep intestinal metaplasia or any degree of dysplasia, we found no
      statistically significant associations with any genotype from these loci for
      dominant, additive, or recessive inheritance models. There was no statistically
      significant evidence of multiplicative interactions between any pair of genotypes
      based on CYP2E1 RsaI, CYP2E1 DraI, GSTP1, GSTM1, or GSTT1; nor between
      Helicobacter pylori status and any of these five loci; nor between smoking status
      and GSTP1, GSTM1, or GSTT1; nor between alcohol consumption and ALDH2.
      Statistically significant interactions were noted between salt consumption and
      GSTP1 and between sour pancake consumption and CYP2E1 RsaI. There was, moreover,
      a statistically significant interaction (odds ratio, 1.78; 95% confidence
      interval, 1.03-3.08) between CYP2E1 DraI and smoking at least one cigarette per
      day. A positive but not statistically significant interaction was also seen
      between CYP2E1 RsaI and smoking status. These polymorphisms do not seem to govern
      progression from mild chronic atrophic gastritis to advanced precancerous gastric
      lesions, but the effects of smoking may be accentuated in individuals carrying
      variants of CYP2E1.

PMID- 15734973
TI  - Obesity, recreational physical activity, and risk of pancreatic cancer in a large
      U.S. Cohort.
AB  - BACKGROUND: Obesity and physical activity, in part through their effects on
      insulin sensitivity, may be modifiable risk factors for pancreatic cancer.
      METHODS: The authors analyzed data from the American Cancer Society Cancer
      Prevention Study II Nutrition Cohort to examine the association between measures
      of adiposity, recreational physical activity, and pancreatic cancer risk.
      Information on current weight and weight at age 18, location of weight gain, and
      recreational physical activity were obtained at baseline in 1992 via a self
      administered questionnaire for 145,627 men and women who were cancer-free at
      enrollment. During the 7 years of follow-up, 242 incident pancreatic cancer cases
      were identified among these participants. Cox proportional hazards modeling was
      used to compute hazard rate ratios (RR) and to adjust for potential confounding
      factors including personal history of diabetes and smoking. RESULTS: We observed
      an increased risk of pancreatic cancer among obese [body mass index (BMI) >/= 30]
      men and women compared with men and women of normal BMI [<25; RR, 2.08; 95%
      confidence interval (95% CI), 1.48-2.93, P(trend) = 0.0001]. After adjustment for
      between BMI, risk of pancreatic cancer was independently increased among men and
      women who reported a tendency for central weight gain compared with men and women
      reporting a tendency for peripheral weight gain (RR, 1.45; 95% CI, 1.02-2.07). We
      observed no difference in pancreatic cancer incidence rates between men and women
      who were most active (>31.5 metabolic equivalent hours per week) at baseline
      compared with men and women who reported no recreational physical activity (RR,
      1.20; 95% CI, 0.63-2.27). CONCLUSION: This study, along with several recent
      studies, supports the hypothesis that obesity and central adiposity are
      associated with pancreatic cancer risk.

PMID- 15734974
TI  - Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a
      systematic review.
AB  - Mucosal human papillomaviruses (HPV) are the cause of cervical cancer and likely
      a subset of head and neck squamous cell carcinomas (HNSCC), yet the global
      prevalence and type distribution of HPV in HNSCC remains unclear. We
      systematically reviewed published studies of HNSCC biopsies that employed PCR
      based methods to detect and genotype HPV to describe the prevalence and type
      distribution of HPV by anatomic cancer site. Geographic location and study size
      were investigated as possible sources of variability. In the 5,046 HNSCC cancer
      specimens from 60 studies, the overall HPV prevalence was 25.9% [95% confidence
      interval (95% CI), 24.7-27.2]. HPV prevalence was significantly higher in
      oropharyngeal SCCs (35.6% of 969; 95% CI, 32.6-38.7) than oral SCCs (23.5% of
      2,642; 95% CI, 21.9-25.1) or laryngeal SCCs (24.0% of 1,435; 95% CI, 21.8-26.3).
      HPV16 accounted for a larger majority of HPV-positive oropharyngeal SCCs (86.7%;
      95% CI, 82.6-90.1) compared with HPV-positive oral SCCs (68.2%; 95% CI, 64.4
      71.9) and laryngeal SCCs (69.2%; 95% CI, 64.0-74.0). Conversely, HPV18 was rare
      in HPV-positive oropharyngeal SCCs (2.8%; 95% CI, 1.3-5.3) compared with other
      head and neck sites [34.1% (95% CI, 30.4-38.0) of oral SCCs and 17.0% (95% CI,
      13.0-21.6) of laryngeal SCCs]. Aside from HPV16 and HPV18, other oncogenic HPVs
      were rarely detected in HNSCC. Tumor site-specific HPV prevalence was higher
      among studies from North America compared with Europe and Asia. The high HPV16
      prevalence and the lack of HPV18 in oropharyngeal compared with other HNSCCs may
      point to specific virus-tissue interactions. Small sample size and publication
      bias complicate the assessment of the prevalence of HPV in head and neck sites
      beyond the oropharynx.

PMID- 15734975
TI  - The ADH1C polymorphism modifies the risk of squamous cell carcinoma of the head
      and neck associated with alcohol and tobacco use.
AB  - Alcohol consumption interacts with tobacco use to increase the risk of head and
      neck squamous cell carcinoma (HNSCC). Alcohol is eliminated through oxidation by
      alcohol dehydrogenase (ADH). The ADH1C gene is polymorphic and the ADH1C*1 allele
      metabolizes ethanol to acetaldehyde at a higher rate than the variant ADH1C*2
      allele. This polymorphism has been reported to alter the risk of HNSCC associated
      with alcohol use, although the literature differs in the estimates of both the
      magnitude and direction of this effect modification. We have investigated the
      association between the established risk factors for HNSCC and variant genotypes
      of ADH1C in a case-control study in the greater Boston area. ADH1C genotypes were
      determined from 521 cases and 599 population-based controls. The odds ratio (OR)
      for HNSCC associated with >26 drinks per week was 3.7 [95% confidence interval
      (95% CI), 2.4-5.7], whereas the OR for smoking >58 pack-years was 5.6 (95% CI,
      3.8-8.4). The combination of heavy smoking and heavy drinking significantly
      interacted to produce an OR of 17.3 (95% CI, 7.8-38.3). In cases and controls,
      respectively, 16% and 14% were ADH1C*1-1, 46% and 46% were ADH1C*1-2 and 38% and
      40% were ADH1C*2-2. There was a significant interaction of alcohol use and
      genotype (P = 0.05), with an estimated oral cancer risk in heavy drinkers of 7.1
      (95% CI, 2.3-22.0) for homozygous variants compared with an OR of 2.3 (95% CI,
      1.4-3.8) for ADH1C homozygous wild type or heterozygous individuals (controlling
      for smoking, age, race, and gender). These findings suggest that the ADH1C*2-2
      genotype is associated with susceptibility to smoking and drinking-related HNSCC
      by modifying the biologically effective dose of alcohol.

PMID- 15734976
TI  - Dietary patterns associated with male lung cancer risk in the Netherlands Cohort
      Study.
AB  - The objective of this article was to study the association between dietary
      patterns and lung cancer incidence in the Netherlands Cohort Study on Diet and
      Cancer. The baseline measurement of this prospective case cohort study that was
      completed by 58,279 men in 1986 included a self-administered questionnaire on
      dietary intake, smoking habits, and other covariates. Follow-up was established
      by computerized record linkage to cancer registries and a pathology register.
      After 9.3 years of follow-up, 1,426 confirmed cases of incident male lung cancer
      were detected. Five dietary patterns were identified by exploratory factor
      analysis in a randomly sampled subcohort (n = 2,190). The dietary pattern labeled
      "salad vegetables" was associated with decreased risk of lung cancer [rate ratios
      (RR)(Q5), 0.75; 95% confidence interval (CI), 0.55-1.01], after multivariate
      adjustment. This inverse association was most evident among current and former
      smokers. A dietary pattern labeled "sweet foods" was also inversely associated
      with lung cancer risk (RR(Q5), 0.62; 95% CI, 0.43-0.89). However, the higher
      intake of monosaccharides and disaccharides, fruits, and lower consumption of
      alcohol associated with this pattern could not account for its full protective
      effect. The "pork, processed meat, and potatoes" pattern was nonsignificantly
      associated with increased risk (RR(Q5), 1.44; 95% CI, 0.99-2.09), and this
      positive association was most evident among current smokers. The other dietary
      patterns characterized by brown/white bread substitution and by consumption of
      cooked vegetables were not associated with lung cancer risk. These results show
      how studying both single factors and dietary patterns gives more insight into the
      complex, and often seemingly inconsistent, associations between diet and cancer.

PMID- 15734977
TI  - Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of
      lung cancer.
AB  - Cigarette smoking may induce DNA damage. Lower DNA repair capacities have been
      associated with higher risk of lung cancer. Excision repair cross-complementing
      group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process, and
      low expression of ERCC1 mRNA levels has been associated with higher risk of
      cancers. We examined the association between two polymorphisms of ERCC1, 8092C >
      A (rs3212986) and 19007T > C (codon 118, rs11615), which are associated with
      altered ERCC1 mRNA stability and mRNA levels, in 1,752 Caucasian lung cancer
      patients and 1,358 controls. The results were analyzed using logistic regression
      models, adjusting for relevant covariates. The two polymorphisms were in Hardy
      Weinberg disequilibrium and in linkage disequilibrium. There was no overall
      association between ERCC1 polymorphisms and lung cancer risk, with the adjusted
      odds ratios (AOR) of 1.26 [95% confidence interval (95% CI), 0.81-1.96] for the
      8092C > A polymorphism (A/A versus C/C) and 0.93 (95% CI, 0.67-1.30) for the
      19007T > C polymorphism (C/C versus T/T). Stratified analyses revealed that the
      AORs for the 8092C > A polymorphism (A/A versus C/C) decreased significantly as
      pack-years increased, with the AOR of 2.11 (95% CI, 1.03-4.31) in never smokers
      and 0.50 (95% CI, 0.25-1.01) in heavy smokers (>/=56 pack-years), respectively.
      Consistent results were found when gene-smoking interaction was incorporated by
      joint effects and interactions models that considered both discrete and
      continuous variables for cumulative smoking exposure. The same direction for the
      gene-smoking interaction was found for the 19007T > C polymorphism, although the
      interaction was not statistically significant. In conclusion, ERCC1 8092C > A
      polymorphism may modify the associations between cumulative cigarette smoking and
      lung cancer risk.

PMID- 15734978
TI  - Interindividual variability in response to sodium dichromate-induced oxidative
      DNA damage: role of the Ser326Cys polymorphism in the DNA-repair protein of 8-oxo
      7,8-dihydro-2'-deoxyguanosine DNA glycosylase 1.
AB  - Although the genotoxic mechanism(s) of hexavalent chromium (CrVI) carcinogenicity
      remain to be fully elucidated, intracellular reduction of CrVI and concomitant
      generation of reactive intermediates including reactive oxygen species and
      subsequent oxidative damage to DNA is believed to contribute to the process of
      carcinogenesis. In the current study, substantial interindividual variation (7.19
      25.84% and 8.79-34.72% tail DNA as assessed by conventional and FPG-modified
      comet assay, respectively) in levels of DNA strand breaks after in vitro
      treatment of WBC with sodium dichromate (100 micromol/L, 1 hour) was shown within
      a group of healthy adult volunteers (n = 72) as assessed by both comet and
      formamidopyrimidine glycosylase-modified comet assays. No statistically
      significant correlation between glutathione S-transferases M1 or T1, NADPH
      quinone oxidoreductase 1 (codon 187) and X-ray repair cross complementation
      factor 1 (codon 194) genotypes and individual levels of DNA damage were observed.
      However, individuals homozygous for the Cys(326) 8-oxo 7,8-dihydro-2'
      deoxyguanosine glycosylase 1 (OGG1) polymorphism had a statistically significant
      elevation of formamidopyrimidine glycosylase-dependent oxidative DNA damage after
      treatment with sodium dichromate when compared with either Ser(326)/Ser(326) or
      Ser(326)/Cys(326) individuals (P = 0.008 and P = 0.003, respectively). In
      contrast, no effect of OGG1 genotype on background levels of oxidative DNA damage
      was observed. When individuals were divided on the basis of OGG1 genotype,
      Cys(326)/Cys(326) individuals had a statistically significant (P < 0.05, one-way
      ANOVA followed by Tukey test) higher ratio of oxidative DNA damage to plasma
      antioxidant capacity than either Ser(326)/Ser(326) or Ser(326)/Cys(326)
      individuals. The results of this study suggest that the Cys(326)/Cys(326) OGG1
      genotype may represent a phenotype that is deficient in the repair of 8-oxo-7,8
      dihydro-2'-deoxyguanosine, but only under conditions of cellular oxidative
      stress. We hypothesize that this may be due to oxidation of the Cys(326) residue.
      In conclusion, the homozygous Cys(326) genotype may represent a biomarker of
      individual susceptibility of lung cancer risk in individuals that are
      occupationally exposed to CrVI.

PMID- 15734979
TI  - Chromosomal aberrations in cord blood are associated with prenatal exposure to
      carcinogenic polycyclic aromatic hydrocarbons.
AB  - Molecular and traditional epidemiology studies have indicated a possible
      relationship between in utero environmental exposures and increased risk for
      childhood cancers, especially acute leukemias. Chromosomal aberrations have been
      associated with environmental exposures and cancer risk in adults. In order to
      more clearly define the association between prenatal exposures to carcinogenic
      polycyclic aromatic hydrocarbons (PAH) and chromosomal aberrations, chromosomal
      aberration frequencies were measured in a subset of 60 newborns from the Columbia
      Center for Children's Environmental Health (CCCEH) Prospective Cohort Study. The
      subset was composed of African American and Dominican, nonsmoking mother-newborn
      pairs residing in low-income neighborhoods of New York City, who were exposed to
      varying levels of airborne PAHs. Prenatal exposure was assessed by questionnaire,
      personal air monitoring during the third trimester, and PAH-DNA adducts in
      umbilical cord blood. Chromosomal aberrations were measured in cord blood
      lymphocytes by fluorescence in situ hybridization. PAH-DNA adducts were not
      associated with chromosomal aberrations. However, airborne PAHs were
      significantly associated with stable aberration frequencies in cord blood (P <
      0.01). Moreover, stable aberration frequencies were significantly higher among
      African American newborns compared with Dominican, despite no significant
      differences in PAH exposure. These results show for the first time an association
      between prenatal exposure to airborne carcinogenic PAHs and chromosomal
      aberrations in cord blood, suggesting that such prenatal exposures have the
      potential to cause cytogenetic damage that has been related to increased cancer
      risk in other populations. If confirmed, this finding may open new avenues for
      prevention.

PMID- 15734980
TI  - Dietary factors and risk of non-hodgkin lymphoma in men and women.
AB  - BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has increased worldwide
      in recent decades. Diet could influence NHL risk by modulating the immune system,
      although evidence is limited. We did a population-based case-control study to
      determine whether differences in diet were associated with NHL risk. METHODS: A
      total of 597 NHL cases and 467 population controls in Sweden completed a
      semiquantitative food frequency questionnaire evaluating their dietary habits 2
      years before the interview. Unconditional logistic regression was used to
      estimate the odds ratios (OR) and corresponding 95% confidence intervals (95% CI)
      for associations between food intake and risk of NHL. RESULTS: High consumption
      of dairy products and fried red meat was associated with increased risk of NHL.
      The OR of NHL for individuals in the highest quartile compared with the lowest
      quartile of dairy intake was 1.5 (95% CI, 1.1-2.2; P(trend) = 0.003). The OR for
      the highest versus lowest quartile of fried red meat intake was 1.5 (95% CI, 1.0
      2.1; P(trend) = 0.02). In contrast, high consumption of fruits and vegetables was
      associated with reduced risk of NHL, particularly follicular lymphoma, among
      women but not men. Compared with the lowest quartile of vegetable intake, the OR
      of follicular lymphoma among women in the highest quartile of vegetable intake
      was 0.3 (95% CI, 0.1-0.7; P(trend) = 0.002). CONCLUSIONS: The positive
      associations of NHL risk with dairy products and fried red meat and the inverse
      association with fruits and vegetables suggest that diet affects NHL risk and
      could explain the increase of some histopathogic subtypes.

PMID- 15734981
TI  - Antibody responses to simian virus 40 T antigen: a case-control study of non
      Hodgkin lymphoma.
AB  - A possible role for SV40, a macaque polyomavirus, in non-Hodgkin lymphoma (NHL)
      in humans was raised recently by the reported detection of SV40 DNA in tumor
      tissue. Animals with SV40-induced tumors frequently produce high-level antibodies
      against T antigen, the SV40 oncoprotein. In this study, we assessed whether SV40
      T antibody measured in humans supported a relationship between SV40 and NHL.
      Subjects were sampled from a U.S. population-based case-control study of NHL,
      according to presence of antibodies against capsids of SV40 and BK, a related
      human polyomavirus (n = 85 cases, n = 95 controls). T antibody was measured by
      enzyme immunoassay. We also evaluated serum specimens from SV40-infected and SV40
      uninfected macaques (n = 19 and n = 8, respectively), SV40-uninfected hamsters (n
      = 5), and hamsters with SV40-induced tumors (n = 10). Hamsters with SV40-induced
      tumors all produced robust SV40 T antibody [median absorbance, 0.99), whereas
      SV40-uninfected hamsters and macaques had much lower levels (median absorbance,
      0.05 and 0.04, respectively). NHL cases, controls, and SV40-infected macaques
      resembled these latter two groups, generally showing only low-level T antibody
      (median absorbance, 0.03, 0.04, and 0.04, respectively). Overall, only five cases
      (6%) and five controls (5%) had T antibody responses classified as seropositive
      (odds ratio, 1.2; 95% confidence interval, 0.3-4.6). Interestingly, all 10 humans
      with T antibody responses also showed antibody responses to BK capsid. We found
      no association between the presence of T antibody and NHL, arguing against SV40
      as a cause of NHL. Infrequent and low-level T antibody responses among humans
      could represent cross-reactivity to BK virus T antigen.

PMID- 15734982
TI  - Calcium, vitamin D, and apoptosis in the rectal epithelium.
AB  - OBJECTIVE: Decreased apoptosis in the colon is potentially an early indicator of
      colon cancer risk and may be influenced by calcium and vitamin D. This report
      describes the associations of calcium intake and 25-hydroxyvitamin D levels with
      apoptosis in colorectal epithelium. METHODS: Consecutive patients undergoing
      colonoscopies were recruited for a study designed to examine risk and etiologic
      factors for colorectal adenomas. Diet was assessed by food frequency
      questionnaire, and in one subpopulation, serum 25-hydroxyvitamin D levels were
      measured using an enzyme immunoassay. Apoptosis was scored from normal rectal
      mucosal pinch biopsies. Linear and logistic regression analyses were used to
      examine associations between calcium, serum vitamin D, and apoptotic scores. Data
      were available for 498 and 280 patients for the calcium and vitamin D analyses,
      respectively. RESULTS: Associations of calcium intake and vitamin D with
      apoptosis were modified by adenoma case-status. In an adjusted logistic
      regression model, patients with adenomas in the highest versus lowest tertile of
      dietary calcium intake had 3.4 times higher odds [95% confidence interval (CI),
      0.9-12.9] of elevated apoptotic scores. In adenoma-free patients, high calcium
      intake was not related to apoptosis (OR, 1.2; 95% CI, 0.6-2.7). In contrast, the
      highest level of 25-hydroxyvitamin D was associated with higher apoptosis in
      adenoma-free patients (OR, 2.6; 95% CI, 1.1-6.2) and slightly lower levels in
      patients with adenomas (OR, 0.6; 95% CI, 0.2-2.2). CONCLUSION: These results are
      consistent with a calcium and vitamin D-mediated apoptotic mechanism in colon
      carcinogenesis.

PMID- 15734984
TI  - A digital image analysis system for identifying filter vent blocking on
      ultralight cigarettes.
AB  - Filter ventilation is the dominant design feature on modern cigarettes, diluting
      the mainstream smoke with air and reducing tar and nicotine yields in the
      standard assay. Smokers are generally unaware of vent holes and often cover them
      with lips or fingers while smoking, reducing or eliminating the air dilution
      effect and increasing intake of tar and nicotine particularly on ultra-low tar
      brands. A digital imaging and analysis system for the detection of vent blocking
      was developed. Two studies were designed to evaluate the effectiveness of three
      color measures (hue, saturation, and value) at discriminating whether at least
      50% blocking had occurred. In study 1, saturation showed perfect discrimination
      between unblocked Carlton butts and butts with at least 50% of the vents blocked
      during syringe smoking. In study 2, saturation showed 95% accuracy at identifying
      Marlboro Ultra Light butts with at least four puffs blocked by smokers' lips. The
      results indicate that the pattern of color saturation is related to vent
      blocking. Implications for tobacco control research and policy are discussed.

PMID- 15734983
TI  - A model-based comparison of breast cancer screening strategies: mammograms and
      clinical breast examinations.
AB  - In screening for secondary prevention of breast cancer, clinical breast
      examination (CBE) combined with mammography may improve overall screening
      sensitivity compared with mammography alone. A systematic evaluation of the
      relative expenses and projected benefit of combining these two screening
      modalities is not presently available. We addressed this issue using a
      microsimulation model incorporating age-specific preclinical duration of the
      disease, age-specific sensitivities of the two modalities, age-specific incidence
      of the disease, screening strategy, and competing causes of mortality. We
      examined a total of 48 screening strategies, depending on the age range, the
      examination interval, and whether mammography or CBE is given at every one or two
      exam. Our results indicate that a biennial mammography can be cost-effective if
      coupled with annual CBE. For each screening interval and starting age, giving
      mammography every two exams and CBE at every exam has the lowest marginal cost
      per year of quality-adjusted life saved, whereas giving both at every exam has
      the highest. Comparing annual mammography and CBE to biennial mammography and
      annual CBE from 50 to 79, the total cost was reduced by 35%, whereas the marginal
      quality-adjusted life years only decreased by 12%. Similar reductions are
      observed for other starting ages. It is cost-effective to have a biennial
      mammography if coupled with an annual CBE. Annual mammography combined with CBE
      every 6 months will lead to a 41% increase in the quality-adjusted life years
      compared with annual mammography and CBE from 50 to 79, whereas the total cost
      increases by 30%.

PMID- 15734985
TI  - Lack of association between polymorphisms in inflammatory genes and lung cancer
      risk.

PMID- 15734986
TI  - 4-Hydroxy-1-(3-pyridyl)-1-butanone, an indicator for 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone-induced DNA damage, is not detected in human pancreatic
      tissue.

PMID- 15734987
TI  - Medication use, medical conditions, and the risk of human papillomavirus
      infection and subsequent cervical intraepithelial neoplasia 3 among women with
      mild cytologic abnormalities.

PMID- 15734988
TI  - Gastric and duodenal ulcer and risk of bladder cancer.

PMID- 15734989
TI  - Epidemiology of urinary melatonin in women and its relation to other hormones and
      night work.

PMID- 15734990
TI  - Number of siblings and risk of hodgkin's and other lymphoid neoplasms.

PMID- 15734991
TI  - Molecular target-based treatment of human cancer: summary of the 10th
      international conference on differentiation therapy.
AB  - The 10th International Conference on Differentiation Therapy was held between
      April 29 and May 3, 2004, in Shanghai, China. In the tradition of previous
      conferences from this series, which have been held biannually since the first
      meeting organized 20 years ago by Samuel Waxman and Giovanni Rossi in Sardinia,
      the organizers of the 10th International Conference on Differentiation Therapy
      aimed to gather basic and clinical cancer investigators in a setting of plenary
      sessions, workshops, and poster presentations to maximize the effective exchange
      of information and foster the establishment of collaborative interactions.
      Approximately 300 scientists attended the meeting with a mission to discuss
      targeted approaches to cancer treatment, which stem from our understanding of
      basic biological processes and the mechanisms of their deregulation during
      tumorigenesis.

PMID- 15734992
TI  - Osterix, a transcription factor for osteoblast differentiation, mediates
      antitumor activity in murine osteosarcoma.
AB  - Osterix is a novel zinc finger-containing transcription factor that is essential
      for osteoblast differentiation and bone formation. We hypothesized that osterix
      might have a role in osteosarcoma tumor growth and metastasis. Northern blot
      analysis showed that the mRNA level of osterix was decreased in two mouse
      osteosarcoma cell lines compared with its level in normal mouse osteoblasts.
      Osterix expression was also decreased in three human osteosarcoma cell lines.
      Transfection of the osx gene into the mouse osteosarcoma cells inhibited tumor
      cell growth in vitro and in vivo and significantly reduced tumor incidence, tumor
      volume, and lung metastasis following intratibial injection. Osterix expression
      was also associated with decreased osteolysis. Using an in vitro migration assay,
      osterix suppressed the migration of tumor cells to lung extracts. These results
      suggest that osterix expression may play a role in osteosarcoma tumor growth and
      metastasis.

PMID- 15734993
TI  - Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast
      activation and bone destruction by cancer cells.
AB  - The bone is the third most common site of cancer metastasis. To invade the bone,
      tumor cells produce osteoclast-activating factors that increase bone resorption
      by osteoclasts. Here we report that human neuroblastoma cells that form
      osteolytic lesions in vivo do not produce osteoclast-activating factors but
      rather stimulate osteoclast activity in the presence of human bone marrow
      mesenchymal stem cells. This alternative pathway of osteoclast activation
      involves a nonadhesive interaction between neuroblastoma cells and bone marrow
      mesenchymal stem cells. Stimulated bone marrow mesenchymal stem cells express
      markedly increased levels of interleukin-6, which is then responsible for
      osteoclast activation. This report describes a critical role of bone marrow
      mesenchymal stem cells in bone destruction in cancer.

PMID- 15734994
TI  - Effects of DNA methylation on galectin-3 expression in pituitary tumors.
AB  - Galectin-3 (Gal-3), a beta-galactoside-binding protein is expressed in a specific
      cell-type manner in pituitary tumors. Here we questioned the mechanism of Gal-3
      expression in pituitary tumors, by using methylation-specific PCR and DNA
      sequence analyses to analyze the methylation status of the promoter region of the
      LGALS3 gene. DNA analysis of a human pituitary tumor, breast carcinoma cell
      lines, and thyroid carcinoma cell lines showed that in cells expressing Gal-3
      protein, the LGALS3 gene was unmethylated, whereas in Gal-3 null cells, the
      promoter of the LGALS3 gene was methylated. Treatment of cells with 30 mumol/L 5
      aza-2'-deoxycytidine induced Gal-3 mRNA and protein expression. Among pituitary
      tumors, 30% (7/23), mainly in follicle-stimulating hormone/luteinizing hormone
      producing (38%) and null cell (57%) adenomas, the promoter of the LGALS3 was
      found to be methylated and silenced, although prolactin- and adrenocorticotropic
      hormone-producing tumors, which were unmethylated, expressed the Gal-3 protein.
      These results show for the first time that Gal-3 expression is regulated in part
      by promoter methylation in pituitary as well as in other tumors. Because it is
      functionally involved in cancer progression and metastasis, Gal-3 may serve as a
      possible therapeutic target in the treatment of pituitary tumors.

PMID- 15734995
TI  - Circulating tumor-specific DNA: a marker for monitoring efficacy of adjuvant
      therapy in cancer patients.
AB  - Adjuvant systemic therapy (a strategy that targets potential disseminated tumor
      cells after complete removal of the tumor) has clearly improved survival of
      patients with cancer. To date, no tool is available to monitor efficacy of these
      therapies, unless distant metastases arise, a situation that unavoidably leads to
      death. We analyzed RASSF1A DNA methylation in pretherapeutic sera and serum
      samples collected 1 year after surgery from 148 patients with breast cancer who
      were receiving adjuvant tamoxifen; 19.6% and 22.3% of patients with breast cancer
      showed RASSF1A DNA methylation in their pretherapeutic and 1-year-after serum
      samples, respectively. RASSF1A methylation 1 year after primary surgery (and
      during adjuvant tamoxifen therapy) was an independent predictor of poor outcome,
      with a relative risk (95% confidence interval) for relapse of 5.1 (1.3-19.8) and
      for death of 6.9 (1.9-25.9). Measurement of serum DNA methylation allows adjuvant
      systemic treatment to be monitored for efficacy: disappearance of RASSF1A DNA
      methylation in serum throughout treatment with tamoxifen indicates a response,
      whereas persistence or new appearance means resistance to adjuvant tamoxifen
      treatment. It remains to be seen whether modifications made in adjuvant
      therapeutic strategies based on detection of circulating nucleic acids will
      improve survival as well as quality of life.

PMID- 15734996
TI  - Haploinsufficiency for odc modifies mouse skin tumor susceptibility.
AB  - Numerous studies have linked overexpression of ornithine decarboxylase (Odc) gene
      with enhanced susceptibility to mouse skin tumorigenesis. However, there is
      little experimental evidence suggesting that modest reductions in Odc expression
      might reduce tumor susceptibility. To address this issue, here we report the use
      of the Odc(+/-) haploinsufficiency model, in which one copy of the murine Odc
      gene has been inactivated by a homologous recombination. Compared with Odc(+/+)
      mice, Odc(+/-) mice exhibit reduced epidermal ODC enzyme activity and polyamine
      accumulation following treatment with the tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA). Furthermore, following chronic TPA
      treatment, the characteristic hyperplastic response of the epidermis was
      diminished in Odc(+/-) mice. Finally, when subjected to a two-stage initiation
      promotion protocol, substantially fewer skin papillomas developed in Odc(+/-)
      mice compared with wild-type littermates. These results support the concept that
      differences in tissue polyamine levels, resulting from either overexpression or
      reductions in ODC, are important modifiers of tumor susceptibility.

PMID- 15734997
TI  - Differential expression of cell cycle regulators in phenotypic variants of
      transgenically induced bladder tumors: implications for tumor behavior.
AB  - Proteins controlling cell growth, differentiation, apoptosis, and oncogenic
      stress are often deregulated in tumor cells. However, whether such deregulations
      affect tumor behavior remains poorly understood in many tumor types. We recently
      showed that the urothelium-specific expression of activated H-ras and SV40 T
      antigen in transgenic mice produced two distinctive types of tumors strongly
      resembling the human superficial papillary tumors and carcinoma in situ of the
      bladder, respectively. Here we assessed the expression of a key set of cell cycle
      regulators in these mouse tumors and in a new transgenic line expressing a cyclin
      D1 oncogene in the urothelium. We found that urothelia of the wild-type and
      cyclin D1 transgenic mice exhibited a profile of cell cycle regulators found in
      quiescent (G(0)) cells, indicating that urothelium overexpressing the cyclin D1
      (an 8-fold increase) is reminiscent of normal urothelium and remains slow
      cycling. Low-grade superficial papillary tumors induced by activated H-ras had no
      detectable Rb family proteins (Rb, p107, and p130) and late cell cycle cyclins
      and kinases (cyclin A, E, and CDK1), but had increased level of p16, p53, and
      MDM2. These data suggest that the inactivation of the Rb pathway plays an
      important role in H-ras-induced superficial papillary tumors and that oncogenic H
      ras can induce a compensatory activation of alternative tumor suppressor
      pathways. In contrast, carcinoma in situ of the bladder induced by SV40 T antigen
      had increased expression of cell cycle regulators mainly active in post-G(1)
      phases. The fact that phenotypically different bladder tumors exhibit different
      patterns of cell cycle regulators may explain why these tumors have different
      propensity to progress to invasive tumors. Our results indicate that the
      transgenic mouse models can be used not only for studying tumorigenesis but also
      for evaluating therapeutic strategies that target specific cell cycle regulators.

PMID- 15734998
TI  - NFBD1/Mdc1 mediates ATR-dependent DNA damage response.
AB  - Budding yeast Rad9 (scRad9) plays a central role in mediating Mec1-dependent
      phosphorylation by recruiting its downstream substrates. The human scRad9
      orthologues 53BP1 and NFBD1 associate with ionizing radiation-induced foci (IRIF)
      at sites of DNA repair. RNAi-based gene silencing of 53BP1 or NFBD1 has shown
      impaired phosphorylation of SQ/TQ [ataxia-telangiectasia mutated/ATM and Rad3
      related (ATM/ATR) substrates] at IRIF, intra-S, and G(2)-M checkpoints and has
      thereby revealed essential roles for 53BP1 and NFBD1 in the DNA damage signaling
      pathway. Whether 53BP1 and NFBD1 are required for activation of kinases and/or
      for recruitment of substrates at IRIF, however, is not clear. Here we show that
      both 53BP1 and NFBD1 are required for recruitment of ATR to DNA damage sites, as
      well as for ATR-dependent phosphorylation in response to DNA damage. NFBD1 is not
      required for ssDNA generation at DNA damage sites and is not recruited by
      replication protein A (RPA)-coated ssDNA. We therefore show that recruitment of
      NFBD1 and/or 53BP1, the factors downstream of H2AX, is independent of ssDNA
      generation and RPA coating, whereas both ssDNA and RPA coating play key roles in
      regulation of the ATR-dependent pathway. These novel findings help clarify where
      NFBD1 functions in DNA damage early responses.

PMID- 15734999
TI  - Deletion, methylation, and expression of the NKX3.1 suppressor gene in primary
      human prostate cancer.
AB  - NKX3.1 is a prostate-specific homeoprotein and tumor suppressor that is affected
      by the loss of 8p21 in prostate cancer. In mice, Nkx3.1 haploinsufficiency
      results in prostatic dysplasia and complements cancer formation induced by loss
      of other suppressor genes. However, NKX3.1 expression can be
      immunohistochemically detected in most primary prostate cancers. We examined the
      relationship between suppressor gene haploinsufficiency, methylation, and
      quantitative NKX3.1 expression levels in primary prostate cancer. NKX3.1 gene
      copy number was assessed by microsatellite analysis, fluorescence in situ
      hybridization, and quantitative PCR. NKX3.1 gene methylation was determined in
      prostate cancer cell lines and we thereby identified potential CpG methylation
      sites for methylation-specific PCR analysis in tissues. We validated and then
      applied an internally controlled fluorescence immunomicroscopic assay for NKX3.1
      protein expression in 48 primary prostate cancer specimens from radical
      prostatectomies. NKX3.1 loss of heterozygosity was found in 27 of 43 tissues
      tested. Classic CpG island methylation of the NKX3.1 gene was not found in either
      prostate cancer cell lines or tissues. However, in 33 of 40 samples tested, CpG
      sites at -921, -903, and -47 were methylated to a greater degree in malignant
      than in adjacent normal cells. In 43 of 48 samples, NKX3.1 protein expression was
      reduced from 0.34 to 0.90 compared with adjacent normal luminal epithelium (mean
      of all samples, 0.68; 95% confidence interval, 0.05). In 12 cases that also had
      high-grade prostatic intraepithelial neoplasia, NKX3.1 expression levels were
      similar in preinvasive and invasive cancer cells and significantly lower than
      adjacent normal cells. Even in the presence of allelic loss, NKX3.1 expression is
      reduced over a wide range in prostate cancer at the time of prostatectomy,
      suggesting that diverse factors influence expression. Samples with protein
      expression below the median level in cancer cells had both NKX3.1 deletion and
      selective CpG methylation.

PMID- 15735000
TI  - Genomic organization of amplified MYC genes suggests distinct mechanisms of
      amplification in tumorigenesis.
AB  - Integration of the human papillomavirus (HPV) genome into the host genome is
      associated with the disruption of the HPV E2 gene and with amplification and
      rearrangement of the viral and flanking cellular sequences. Molecular
      characterization of the genomic structures of coamplified HPV sequences and
      oncogenes provides essential information concerning the mechanisms of
      amplification and their roles in carcinogenesis. Using fluorescent hybridization
      on stretched DNA molecules in two cervical cancer-derived cell lines, we have
      elucidated the genomic structures of amplified regions containing HPV/myc genes
      over several hundreds of kilobases. Direct visualization of hybridization signals
      on individual DNA molecules suggests that overreplication and breakage-fusion
      bridge-type mechanisms are involved in the genomic instability associated with
      HPV cervical cancers. Further analysis from two other genital cancer-derived cell
      lines reveals a recurrent motif of amplification, probably generated by a common
      mechanism involving overreplication upon viral integration. Interestingly,
      different amplification patterns seem to be correlated with the disease outcome,
      thus providing new insights into HPV-related cancer development and tumor
      progression.

PMID- 15735001
TI  - Multiphoton microscopy of endogenous fluorescence differentiates normal,
      precancerous, and cancerous squamous epithelial tissues.
AB  - This study characterizes the morphologic features and the endogenous fluorescence
      in the stratified squamous epithelia of the 7,12-dimethylbenz(a)anthracene
      treated hamster cheek pouch model of carcinogenesis using multiphoton laser
      scanning microscopy (MPLSM). MPLSM allows high-resolution, three-dimensional
      image data to be collected deeper within thick tissue samples with reduced
      phototoxicity compared with single-photon imaging. Three-dimensional image stacks
      of normal (n = 13), precancerous (dysplasia, n = 12; carcinoma in situ, n = 9)
      and cancerous tissue [nonpapillary squamous cell carcinoma (SCC), n = 10, and
      papillary SCC, n = 7] sites in the hamster cheek pouch were collected in viable,
      unsectioned tissue biopsies at a two-photon excitation wavelength of 780 nm. Five
      features were quantified from the MPLSM images. These included nuclear density
      versus depth, keratin layer thickness, epithelial thickness, and the fluorescence
      per voxel in the keratin and epithelial layers. Statistically significant
      differences in all five features were found between normal and both precancerous
      and cancerous tissues. The only exception to this was a lack of statistically
      significant differences in the keratin fluorescence between normal tissues and
      papillary SCCs. Statistically significant differences were also observed in the
      epithelial thickness of dysplasia and carcinoma in situ, and in the keratin layer
      thickness of dysplasia and SCCs (both nonpapillary and papillary). This work
      clearly shows that three-dimensional images from MPLSM of endogenous tissue
      fluorescence can effectively distinguish between normal, precancerous, and
      cancerous epithelial tissues. This study provides the groundwork for further
      exploration into the application of multiphoton fluorescence endoscopy in a
      clinical setting.

PMID- 15735002
TI  - A novel transgenic mouse model reveals humanlike regulation of an 8-kbp human
      TERT gene promoter fragment in normal and tumor tissues.
AB  - Telomerase activity is repressed in most human somatic tissues during
      differentiation processes but strongly up-regulated in most human tumors.
      Regulation of human telomerase activity primarily occurs at the level of
      transcriptional initiation of the TERT gene, which encodes the catalytic subunit
      of telomerase. We have generated a novel transgenic mouse model to study the
      regulation of the human TERT gene promoter in an in vivo system. For this
      purpose, we have cloned an 8.0-kbp human TERT promoter fragment in front of the
      bacterial lacZ reporter gene (hTERTp-lacZ), which encodes the beta-galactosidase
      enzyme. Expression of the reporter gene was monitored by reverse transcription
      PCR analysis, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining of
      whole mount preparations, and histologic sections. We find that the activity of
      the human TERT promoter in most normal mouse tissues recapitulates the expression
      of the hTERT gene in normal human tissues and is under tighter control when
      compared with the endogenous mouse TERT gene expression. In testis, where highest
      lacZ expression was observed, the expression of the reporter gene was restricted
      to the spermatogonial stem cells and the spermatocytes. Intriguingly, we find
      increased levels of lacZ expression in mammary tumors of hTERTp-lacZ x p53(+/-)
      bitransgenic mouse mammary tumor model. Thus, this transgenic mouse model
      provides a suitable in vivo system to analyze the expression of the human TERT
      gene under physiologic conditions and during tumorigenesis.

PMID- 15735003
TI  - p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival
      pathway.
AB  - Although a number of p53 target genes have been identified, the mechanisms of p53
      dependent activities that determine cellular survival or death are still not
      fully understood. Here we report isolation of a novel p53 target gene, designated
      p53-inducible cell-survival factor (p53CSV). p53CSV contains a p53-binding site
      within its second exon and the reduction of expression by small interfering RNA
      enhanced apoptosis, whereas overexpression protected cells from apoptosis caused
      by DNA damage. p53CSV is induced significantly when cells have a low level of
      genotoxic stresses, but not when DNA damage is severe. p53CSV can modulate
      apoptotic pathways through interaction with Hsp70 that probably inhibits activity
      of apoptosis protease activating factor-1. Our results imply that under specific
      conditions of stress, p53 regulates transcription of p53CSV and that p53CSV is
      one of the important players in the p53-mediated cell survival.

PMID- 15735004
TI  - Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer.
AB  - Chromosomal deletions are often observed in lung cancers suggesting that
      inactivation of tumor suppressor genes plays an important role in the development
      of this neoplasm. The region around chromosome 8p22 is a frequent and early
      target of these deletions and has therefore been investigated for the presence of
      candidate genes. The FEZ1/LZTS1 gene, located at 8p22, is inactivated in many
      cancers with 8p deletions, including prostate, esophageal, gastric, bladder, and
      breast cancer and the Fez1 protein has been shown to suppress growth of cancer
      cells and to regulate mitosis. To elucidate the role of FEZ1 in lung cancer, we
      have analyzed its expression by immunohistochemistry in 103 primary lung cancer
      specimens including 98 non-small cell lung cancers (57 adenocarcinomas, 32
      squamous cell carcinomas, 7 large cell carcinomas, and 2 others) and five small
      cell carcinomas. Absence of Fez1 protein expression was observed in 27 cases
      (26%) and additional 43 cases (42%) showed strong reduction in immunoreactivity.
      There was a positive association between loss of FEZ1 expression and tumor
      grading (P = 0.0345) and a tendency toward a reduction in the mortality rate in
      subjects with strong FEZ1 expression. Overall, these data indicate an important
      role for FEZ1 in lung cancer and suggest the possibility that it may serve as a
      novel prognostic indicator.

PMID- 15735006
TI  - p53 modulates RPA-dependent and RPA-independent WRN helicase activity.
AB  - Werner syndrome is a hereditary disorder characterized by the early onset of age
      related symptoms, including cancer. The absence of a p53-WRN helicase interaction
      may disrupt the signal to direct S-phase cells into apoptosis for programmed cell
      death and contribute to the pronounced genomic instability and cancer
      predisposition in Werner syndrome cells. Results from coimmunoprecipitation
      studies indicate that WRN is associated with replication protein A (RPA) and p53
      in vivo before and after treatment with the replication inhibitor hydroxyurea or
      gamma-irradiation that introduces DNA strand breaks. Analysis of the protein
      interactions among purified recombinant WRN, RPA, and p53 proteins indicate that
      all three protein pairs bind with similar affinity in the low nanomolar range. In
      vitro studies show that p53 inhibits RPA-stimulated WRN helicase activity on an
      849-bp M13 partial duplex substrate. p53 also inhibited WRN unwinding of a short
      (19-bp) forked duplex substrate in the absence of RPA. WRN unwinding of the
      forked duplex substrate was specific, because helicase inhibition mediated by p53
      was retained in the presence of excess competitor DNA and was significantly
      reduced or absent in helicase reactions catalyzed by a WRN helicase domain
      fragment lacking the p53 binding site or the human RECQ1 DNA helicase,
      respectively. p53 effectively inhibited WRN helicase activity on model DNA
      substrate intermediates of replication/repair, a 5' ssDNA flap structure and a
      synthetic replication fork. Regulation of WRN helicase activity by p53 is likely
      to play an important role in genomic integrity surveillance, a vital function in
      the prevention of tumor progression.

PMID- 15735007
TI  - Fate of premalignant clones during the asymptomatic phase preceding lymphoid
      malignancy.
AB  - Almost all cancers are preceded by a prolonged period of clinical latency during
      which a combination of cellular events helps move carcinogen-exposed cells
      towards a malignant phenotype. Hitherto, investigating the fate of premalignant
      cells in vivo remained strongly hampered by the fact that these cells are usually
      indistinguishable from their normal counterparts. Here, for the first time, we
      have designed a strategy able to reconstitute the replicative history of the bona
      fide premalignant clone in an animal model, the sheep experimentally infected
      with the lymphotropic bovine leukemia virus. We have shown that premalignant
      clones are early and clearly distinguished from other virus-exposed cells on the
      basis of their degree of clonal expansion and genetic instability. Detectable as
      early as 0.5 month after the beginning of virus exposure, premalignant cells
      displayed a two-step pattern of extensive clonal expansion together with a
      mutation load approximately 6 times higher than that of other virus-exposed cells
      that remained untransformed during the life span of investigated animals. There
      was no fixation of somatic mutations over time, suggesting that they regularly
      lead to cellular death, partly contributing to maintain a normal lymphocyte count
      during the prolonged premalignant stage. This equilibrium was finally broken
      after a period of 18.5 to 60 months of clinical latency, when a dramatic decrease
      in the genetic instability of premalignant cells coincided with a rapid increase
      in lymphocyte count and lymphoma onset.

PMID- 15735005
TI  - A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor
      suppressor gene and is associated with increased prostate cancer risk.
AB  - Prostate cancer is a leading and increasingly prevalent cause of cancer death in
      men. Whereas family history of disease is one of the strongest prostate cancer
      risk factors and suggests a hereditary component, the predisposing genetic
      factors remain unknown. We first showed that KLF6 is a tumor suppressor
      somatically inactivated in prostate cancer and since then, its functional loss
      has been further established in prostate cancer cell lines and other human
      cancers. Wild-type KLF6, but not patient-derived mutants, suppresses cell growth
      through p53-independent transactivation of p21. Here we show that a germline KLF6
      single nucleotide polymorphism, confirmed in a tri-institutional study of 3,411
      men, is significantly associated with an increased relative risk of prostate
      cancer in men, regardless of family history of disease. This prostate cancer
      associated allele generates a novel functional SRp40 DNA binding site and
      increases transcription of three alternatively spliced KLF6 isoforms. The KLF6
      variant proteins KLF6-SV1 and KLF6-SV2 are mislocalized to the cytoplasm,
      antagonize wtKLF6 function, leading to decreased p21 expression and increased
      cell growth, and are up-regulated in tumor versus normal prostatic tissue. Thus,
      these results are the first to identify a novel mechanism of self-encoded tumor
      suppressor gene inactivation and link a relatively common single nucleotide
      polymorphism to both regulation of alternative splicing and an increased risk in
      a major human cancer.

PMID- 15735008
TI  - Oncogenic K-RAS is required to maintain changes in cytoskeletal organization,
      adhesion, and motility in colon cancer cells.
AB  - RAS oncogenes are thought to play a role at multiple stages of tumorigenesis. The
      role and mechanisms by which RAS oncogenes maintain the transformed state of
      human cancer cells are poorly understood. Here, we have studied the role of
      oncogenic K-RAS in maintaining cytoskeletal disruption, cell adhesion and
      motility in metastatic colon carcinoma cells. Targeted deletion of K-RAS(G13D)
      from HCT116 colon carcinoma cells restored their ability to assemble stress
      fibers and focal adhesions/complexes, accompanied by increased cell-matrix
      adhesion and reduced motility. We further show that oncogenic K-Ras induces high
      Rho activity, but uncouples Rho from stress fiber formation. This uncoupling
      required the maintenance of high levels of the activator protein-1 family member,
      Fra-1, via a mitogen-activated protein/extracellular signal-regulated kinase
      dependent pathway. We also show that PI3-kinase signaling is required for the
      motility of HCT116 cells downstream of oncogenic K-Ras. Our findings suggest that
      mutated K-RAS oncogenes are essential for maintenance of the transformed and
      invasive phenotype of human colon cancer cells.

PMID- 15735010
TI  - Distal Chr 4 harbors a genetic locus (Gct1) fundamental for spontaneous ovarian
      granulosa cell tumorigenesis in a mouse model.
AB  - The spontaneous development of juvenile-onset ovarian granulosa cell tumors in
      mice of the SWXJ-9 recombinant inbred strain is a model for juvenile-type
      granulosa cell tumors that appear in very young girls. To expedite gene discovery
      in this mouse model of childhood cancer, we did a gene mapping study with the
      SWXJ-9 recombinant inbred strain and the evolutionarily divergent Mus musculus
      castaneus (CAST/Ei) strain as a mapping partner. Our mapping strategy focused on
      autosomal determinants of susceptibility with a backcross scheme that exploited a
      paternal, parent-of-origin effect for a X-linked gene (Gct4) that strongly
      supports granulosa cell tumor development. Of 1,968 backcross females examined,
      we detected 81 granulosa cell tumor-bearing animals and compared their allelic
      inheritance patterns to non-tumor-bearing siblings in a case-control analysis.
      The results of our study have confirmed an important locus on mouse chromosome
      (Chr) 4 (Gct1) and have revealed new loci for granulosa cell tumor susceptibility
      (Gct7-Gct9) on Chrs 1, 2, and 13 with susceptibility alleles contributed by the
      SWXJ-9 progenitor. Two novel gene-gene interactions supportive for granulosa cell
      tumor development were also observed between loci on Chrs 17 and 18 and loci on
      Chrs 2 and 10. Our data substantiate the evidence that Gct1 on Chr 4 is a
      fundamental oncogene for granulosa cell tumorigenesis in mice and has identified
      additional interacting autosomal loci that support tumor development.

PMID- 15735009
TI  - Altered gene expression patterns in MCF-7 cells induced by the urban dust
      particulate complex mixture standard reference material 1649a.
AB  - Human exposures to polycyclic aromatic hydrocarbon (PAH) occur in complex
      mixtures. Here, gene expression patterns were investigated using standard
      reference material (SRM) 1649a (urban dust). MCF-7 cells were exposed to SRM
      1649a alone or SRM 1649a with either benzo[a]pyrene (BP) or dibenzo[a,l]pyrene
      (DBP) for 24 hours. Global analyses of the gene expression data revealed
      alterations of 41 RNA transcripts with at least 2-fold change (signal log ratio
      </= -1 or >/= 1) in response to SRM 1649a exposure. Increase in expression of
      cytochrome P450 (CYP) genes was observed in response to BP exposure (CYP1A1 and
      CYP1B1; signal log ratio of 4.7 and 2.5, respectively). An additive induction of
      CYP1A1 and CYP1B1 was observed with cotreatment of SRM 1649a and BP. On the
      contrary, no change in gene expression of CYP1A1 and CYP1B1 was observed when the
      cells were exposed to DBP. Furthermore, to study the effect of complex PAH
      mixtures on the metabolic activation of carcinogenic PAH to DNA-binding
      derivatives and to relate this with gene expression studies, PAH-DNA adduct
      formation was determined. SRM 1649a decreased the total level of BP-DNA adducts
      in comparison with BP alone. No significant difference in adduct levels was
      observed in response to either DBP alone or in combination with SRM 1649a. These
      results provide a transcriptional signature for chemical carcinogen exposure; in
      addition, they suggest a major factor in carcinogenic activity of PAH within
      complex mixtures is their ability to promote or inhibit the activation of
      carcinogenic PAH by the induction of CYP enzymes.

PMID- 15735011
TI  - Susceptibility to aflatoxin B1-induced carcinogenesis correlates with tissue
      specific differences in DNA repair activity in mouse and in rat.
AB  - To investigate the mechanisms responsible for species- and tissue-specific
      differences in susceptibility to aflatoxin B(1) (AFB(1))-induced carcinogenesis,
      DNA repair activities of nuclear extracts from whole mouse lung and liver and rat
      liver were compared, and the ability of in vivo treatment of mice with AFB(1) to
      alter repair of AFB(1)-DNA damage was determined. Plasmid DNA containing AFB(1)
      N(7)-guanine or AFB(1)-formamidopyrimidine adducts were used as substrates for
      the in vitro determination of DNA repair synthesis activity, detected as
      incorporation of radiolabeled nucleotides. Liver extracts from CD-1 mice repaired
      AFB(1)-N(7)-guanine and AFB(1)-formamidopyrimidine adducts 5- and 30-fold more
      effectively than did mouse lung, and approximately 6- and 4-fold more effectively
      than did liver extracts from Sprague-Dawley rats. The susceptibility of mouse
      lung and rat liver to AFB(1)-induced carcinogenesis correlated with lower DNA
      repair activity of these tissues relative to mouse liver. Lung extracts prepared
      from mice treated with a single tumorigenic dose of 50 mg/kg AFB(1) i.p. and
      euthanized 2 hours post-dosing showed minimal incision and repair synthesis
      activities relative to extracts from vehicle-treated mice. Conversely, repair
      activity towards AFB(1)-N(7)-guanine damage was approximately 3.5-fold higher in
      liver of AFB(1)-treated mice relative to control. This is the first study to show
      that in vivo treatment with AFB(1) can lead to a tissue-specific induction in DNA
      repair. The results suggest that lower DNA repair activity, sensitivity of mouse
      lung to inhibition by AFB(1), and selective induction of repair in liver
      contribute to the susceptibility of mice to AFB(1)-induced lung tumorigenesis
      relative to hepatocarcinogenesis.

PMID- 15735012
TI  - Generation and molecular characterization of head and neck squamous cell lines of
      fanconi anemia patients.
AB  - Patients with Fanconi anemia (FA) are prone to develop malignancies at an early
      age. Besides hematologic malignancies, squamous cell carcinomas in the anogenital
      region and head and neck are also frequently found in these patients. The aim of
      this study was to generate a panel of head and neck squamous cell carcinoma
      (HNSCC) cell lines and xenografts of FA HNSCC, and to characterize these cell
      lines in comparison with a panel of seven cell lines from patients with sporadic
      HNSCC. Analyses have been done on sensitivity to DNA cross-linking agents, loss
      of heterozygosity profile, TP53 mutations, TP53 polymorphisms and the presence of
      human papillomavirus. Four FA HNSCC cell lines were established. Sensitivity to
      DNA cross-linking agents (cisplatin) in the FA HNSCC cell lines was on average 10
      times higher as compared with the sporadic HNSCC cell lines. Human papillomavirus
      was not detected in any of the FA or sporadic cell lines. No differences were
      found in loss of heterozygosity pattern, TP53 mutation frequency and TP53
      polymorphism between FA and sporadic HNSCC cell lines. This is the first report
      on the generation of squamous cell lines of FA patients. The FA HNSCC cell lines
      we have generated may be utilized for future studies and might aid in the
      development of new preventive therapies for FA patients. The genetic
      characteristics of these cell lines suggest that FA HNSCC are not very different
      from sporadic HNSCC, except for the sensitivity to cisplatin which is consistent
      with the known cellular FA phenotype.

PMID- 15735013
TI  - Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia.
AB  - The translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML) results in the
      expression of the fusion protein RUNX1/MTG8, which in turn recruits histone
      deacetylases (HDAC) to silence RUNX1 target genes [e.g., interleukin-3 (IL-3)].
      We previously reported that expression of the RUNX1/MTG8 target gene IL-3 is
      synergistically restored by the combination of inhibitors of HDACs (i.e.,
      depsipeptide) and DNA methyltransferases (DNMT; i.e., decitabine) in RUNX1/MTG8
      positive Kasumi-1 cells. Thus, we hypothesized that DNMT1 is also part of the
      transcriptional repressor complex recruited by RUNX1/MTG8. By a chromatin
      immunoprecipitation assay, we identified a RUNX1/MTG8-DNMT1 complex on the IL-3
      promoter in Kasumi-1 cells and in primary RUNX1/MTG8-positive AML blasts. The
      physical association of RUNX1/MTG8 with DNMT1 was shown by coimmunoprecipitation
      experiments. Furthermore, RUNX1/MTG8 and DNMT1 were concurrently released from
      the IL-3 promoter by exposure to depsipeptide or stabilized on the promoter by
      decitabine treatment. Finally, we proved that RUNX1/MTG8 and DNMT1 were
      functionally interrelated by showing an enhanced repression of IL-3 after
      coexpression in 293T cells. These results suggest a novel mechanism for gene
      silencing mediated by RUNX1/MTG8 and support the combination of HDAC and DNMT
      inhibitors as a novel therapeutic approach for t(8;21) AML.

PMID- 15735014
TI  - Ron receptor signaling augments mammary tumor formation and metastasis in a
      murine model of breast cancer.
AB  - The tyrosine kinase receptor Ron has been implicated in several types of cancer,
      including overexpression in human breast cancer. This is the first report
      describing the effect of Ron signaling on tumorigenesis and metastasis in a mouse
      model of breast cancer. Mice with a targeted deletion of the Ron tyrosine kinase
      signaling domain (TK-/-) were crossed to mice expressing the polyoma virus middle
      T antigen (pMT) under the control of the mouse mammary tumor virus promoter. Both
      pMT-expressing wild-type control (pMT+/- TK+/+) and pMT+/- TK-/- mice developed
      mammary tumors and lung metastases. However, a significant decrease in mammary
      tumor initiation and growth was found in the pMT+/- TK-/- mice compared with
      controls. An examination of mammary tumors showed that there was a significant
      decrease in microvessel density, significantly decreased cellular proliferation,
      and a significant increase in terminal deoxynucleotidyl transferase-mediated nick
      end labeling-positive staining in mammary tumor cells from the pMT+/- TK-/- mice
      compared with the pMT+/- TK+/+ mice. Biochemical analyses on mammary tumor
      lysates showed that whereas both the pMT-expressing TK+/+ and TK-/- tumors have
      increased Ron expression compared with normal mammary glands, the pMT-expressing
      TK-/- tumors have deficits in mitogen-activated protein kinase and AKT
      activation. These results indicate that Ron signaling synergizes with pMT
      signaling to induce mammary tumor formation, growth, and metastasis. This effect
      may be mediated in part through the regulation of angiogenesis and through
      proliferative and cell survival pathways regulated by mitogen-activated protein
      kinase and AKT.

PMID- 15735015
TI  - Angiogenesis inhibition by vascular endothelial growth factor receptor-2 blockade
      reduces stromal matrix metalloproteinase expression, normalizes stromal tissue,
      and reverts epithelial tumor phenotype in surface heterotransplants.
AB  - Inhibition of vascular endothelial growth factor (VEGF) signaling, a key
      regulator of tumor angiogenesis, through blockade of VEGF receptor (VEGFR)-2 by
      the monoclonal antibody DC101 inhibits angiogenesis, tumor growth, and invasion.
      In a surface xenotransplant assay on nude mice using a high-grade malignant
      squamous cell carcinoma cell line (A-5RT3), we show that DC101 causes vessel
      regression and normalization as well as stromal maturation resulting in a
      reversion to a noninvasive tumor phenotype. Vessel regression is followed by down
      regulation of expression of both VEGFR-2 and VEGFR-1 on endothelial cells and
      increased association of alpha-smooth muscle actin-positive cells with small
      vessels indicating their normalization, which was further supported by a regular
      ultrastructure. The phenotypic regression of an invasive carcinoma to a well
      demarcated dysplastic squamous epithelium is accentuated by the establishment of
      a clearly structured epithelial basement membrane and the accumulation of
      collagen bundles in the stabilized connective tissue. This normalization of the
      tumor-stroma border coincided with down-regulated expression of the stromal
      matrix metalloproteinases 9 and 13, which supposedly resulted in attenuated
      turnover of extracellular matrix components permitting their structural
      organization. Thus, in this mouse model of a human squamous cell carcinoma cell
      line, blockade of VEGF signaling resulted in the reversion of the epithelial
      tumor phenotype through stromal normalization, further substantiating the crucial
      role of stromal microenvironment in regulating the tumor phenotype.

PMID- 15735016
TI  - Insertion of c-Myc into Igh induces B-cell and plasma-cell neoplasms in mice.
AB  - We used gene targeting in mice to insert a His(6)-tagged mouse c-Myc cDNA,
      Myc(His), head to head into the mouse immunoglobulin heavy-chain locus, Igh, just
      5' of the intronic enhancer, Emu. The insertion of Myc(His) mimicked both the
      human t(8;14)(q24;q32) translocation that results in the activation of MYC in
      human endemic Burkitt lymphomas and the homologous mouse T(12;15) translocation
      that deregulates Myc in certain mouse plasmacytomas. Beginning at the age of 6
      months, Myc(His) transgenic mice developed B-cell and plasma neoplasms, such as
      IgM(+) lymphoblastic B-cell lymphomas, Bcl-6(+) diffuse large B-cell lymphomas,
      and CD138(+) plasmacytomas, with an overall incidence of 68% by 21 months.
      Molecular studies of lymphoblastic B-cell lymphoma, the most prevalent neoplasm
      (50% of all tumors), showed that the lymphomas were clonal, overexpressed
      Myc(His), and exhibited the P2 to P1 promoter shift in Myc expression, a hallmark
      of MYC/Myc deregulation in human endemic Burkitt lymphoma and mouse plasmacytoma.
      Only 1 (6.3%) of 16 lymphoblastic B-cell lymphomas contained a BL-typical point
      mutation in the amino-terminal transactivation domain of Myc(His), suggesting
      that most of these tumors are derived from naive, pregerminal center B cells.
      Twelve (46%) of 26 lymphoblastic B-cell lymphomas exhibited changes in the
      p19(Arf)-Mdm2-p53 tumor suppressor axis, an important pathway for Myc-dependent
      apoptosis. We conclude that Myc(His) insertion into Igh predictably induces B
      cell and plasma-cell tumors in mice, providing a valuable mouse model for
      understanding the transformation-inducing consequences of the MYC/Myc-activating
      endemic Burkitt lymphoma t(8;14)/plasmacytoma T(12;15) translocation.

PMID- 15735017
TI  - Increased expression of the E3-ubiquitin ligase receptor subunit betaTRCP1
      relates to constitutive nuclear factor-kappaB activation and chemoresistance in
      pancreatic carcinoma cells.
AB  - The permanent activation of the transcription factor nuclear factor-kappaB (NF
      kappaB) in pancreatic cancer cells is associated with a profound resistance
      towards chemotherapy. In the present study, we show that chemoresistant
      pancreatic cancer cell lines exhibiting constitutive NF-kappaB activity (i.e.,
      PancTu-1, BxPc3, and Capan-1) express significantly elevated levels of the E3
      ubiquitin ligase receptor subunit betaTRCP1, compared with pancreatic carcinoma
      cell lines lacking constitutive NF-kappaB activity and chemoresistance (i.e.,
      PT45-P1 and T3M4). If transfected with betaTRCP1, PT45-P1 cells exhibit an
      elevated NF-kappaB activity and become less sensitive towards anticancer drug
      treatment (i.e., etoposide). Conversely, blockade of betaTRCP1 expression in
      PancTu-1 cells by transfection with a vector-expressed small interfering RNA
      reduces NF-kappaB activation and chemoresistance. In PancTu-1 cells, betaTRCP1
      expression is inhibited, at least in part, by the interleukin-1 (IL-1)
      receptor(I) antagonist, whereas stimulation of PT45-P1 cells with IL-1beta
      resulted in an increased expression of betaTRCP1, and transfection of this cell
      line with betaTRCP1 induced IL-1beta secretion in a NF-kappaB-dependent fashion.
      Thus, via its close and mutual link to IL-1beta secretion, betaTRCP1 expression
      might substantially contribute to the persistent, IL-1beta-dependent activation
      of NF-kappaB in pancreatic carcinoma cells. In support of this, betaTRCP1
      expression is detectable at considerable levels in a great number of pancreatic
      ductal adenocarcinoma specimens, along with an intense staining for activated NF
      kappaB. Altogether, our findings of the elevated betaTRCP1 expression in
      pancreatic carcinoma cells pinpoint to another important mediator of constitutive
      NF-kappaB activation and thereby of chemoresistance.

PMID- 15735018
TI  - Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by
      blocking basic fibroblast growth factor signaling pathway.
AB  - Dipeptidyl peptidase IV (DPPIV) is a serine protease with tumor suppressor
      function. It regulates the activities of mitogenic peptides implied in cancer
      development. Progression of benign prostate cancer to malignant metastasis is
      linked to increased production of basic fibroblast growth factor (bFGF), a
      powerful mitogen. In this study, using in vitro model system we show that DPPIV
      loss is associated with increased bFGF production in metastatic prostate cancer
      cells. DPPIV reexpression in prostate cancer cells blocks nuclear localization of
      bFGF, reduces bFGF levels, inhibits mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated kinase (ERK)1/2 activation, and decreases levels
      of urokinase-type plasminogen activator, known downstream effectors of bFGF
      signaling pathway. These molecular changes were accompanied by induction of
      apoptosis, cell cycle arrest, inhibition of in vitro cell migration, and
      invasion. Silencing of DPPIV by small interfering RNA resulted in increased bFGF
      levels and restoration of mitogen-activated protein kinase (MAPK)-extracellular
      signal-regulated kinase (ERK)1/2 activation. These results indicate that DPPIV
      inhibits the malignant phenotype of prostate cancer cells by blocking bFGF
      signaling pathway.

PMID- 15735019
TI  - Identification of Src-specific phosphorylation site on focal adhesion kinase:
      dissection of the role of Src SH2 and catalytic functions and their consequences
      for tumor cell behavior.
AB  - Src tyrosine kinase expression and activity are elevated during colon cancer
      progression. How this contributes to the malignant phenotype is not fully
      understood. We show that in KM12C colon carcinoma cells, expression of kinase
      deficient Src proteins (SrcMF and Src251) does not alter cell growth. Src kinase
      activity is required for turnover of cell-matrix adhesions and, in particular,
      the Src-dependent phosphorylation of focal adhesion kinase (FAK) is required for
      their disassembly. Surprisingly, we found that expression of SrcMF or Src251
      resulted in increased tyrosine phosphorylation of FAK on Tyr(407), Tyr(576),
      Tyr(577), and Tyr(861), which are considered to be Src kinase substrates. This
      Src kinase-independent phosphorylation of FAK required an intact Src SH2 domain
      that mediates association of Src and FAK at peripheral adhesions. Use of a novel
      highly potent and selective Src kinase inhibitor AP23464 combined with
      experiments in Src/Fyn/Yes-deficient fibroblasts showed that increased
      phosphorylation of FAK in cells expressing SrcMF did not require Src-like
      kinases. However, specific phosphorylation on Tyr(925) of FAK was not evident in
      SrcMF- or Src251-expressing cells, and lack of Src kinase-dependent
      phosphorylation on this site was associated with impaired adhesion turnover. Our
      data show that Src kinase activity is required for adhesion turnover associated
      with cell migration in cancer cells and that, in addition to the catalytic
      activity, Src also acts as an adaptor to recruit other kinases that can
      phosphorylate key substrates including FAK. These studies have implications for
      tumor progression with respect to the use of Src kinase inhibitors.

PMID- 15735020
TI  - Cytoplasmic domain of proEGF affects distribution and post-translational
      modification of microtubuli and increases microtubule-associated proteins 1b and
      2 production in human thyroid carcinoma cells.
AB  - We studied the distribution of transcripts encoding the cytoplasmic domain of the
      membrane-anchored precursor epidermal growth factor (proEGFcyt) and a novel
      cytoplasmic proEGF splice isoform with a deleted exon 23 and an out-of-frame
      fusion of exon 24 (proEGFdel23) in human normal and neoplastic thyroid tissues.
      In papillary thyroid carcinoma (PTC), coexpression of transcripts encoding for
      both proEGFcyt and proEGFdel23 correlated with poor differentiation of PTC. To
      determine potential roles of the cytoplasmic proEGF domain in human thyroid
      cells, we generated stable transfectants of the human follicular thyroid
      carcinoma cell line FTC-133 overexpressing the normal cytoplasmic domain
      proEGFcyt, a truncated proEGFcyt composed of the peptide sequence encoded by
      exons 22 and 23 (proEGF22.23) and proEGFdel23. The proEGFcyt and proEGF22.23
      transfectants displayed significantly reduced proliferation rates, an enlarged
      cellular phenotype, and alterations in the distribution and post-translational
      modification of the microtubular system. These transfectants also displayed
      increased production of microtubule-associated proteins 1b and 2c, which was
      absent in FTC-133-proEGFdel23 or FTC-133-empty plasmid transfectants. This is the
      first evidence of an involvement of proEGF cytoplasmic domain in microtubular
      stability in the human thyroid carcinoma cell line FTC-133 and may suggest a
      specific role for the cytoplasmic domain of membrane-anchored proEGF,
      particularly exon 23, in thyroid carcinoma. The up-regulation of proEGFdel23 in
      poorly differentiated PTC and the exclusive detection of both proEGF isoforms in
      undifferentiated thyroid carcinoma may indicate an involvement of this novel
      truncated proEGFdel23 cytoplasmic domain during dedifferentiation processes of
      human thyroid cells.

PMID- 15735021
TI  - Angiogenin is translocated to the nucleus of HeLa cells and is involved in
      ribosomal RNA transcription and cell proliferation.
AB  - Angiogenin is an angiogenic protein known to play a role in rRNA transcription in
      endothelial cells. Nuclear translocation of angiogenin in endothelial cells
      decreases as cell density increases and ceases when cells are confluent. Here we
      report that angiogenin is constantly translocated to the nucleus of HeLa cells in
      a cell density-independent manner. Down-regulation of angiogenin expression by
      antisense and RNA interference results in a decrease in rRNA transcription,
      ribosome biogenesis, proliferation, and tumorigenesis both in vitro and in vivo.
      Exogenous angiogenin rescues the cells from antisense and RNA interference
      inhibition. The results showed that angiogenin is constitutively translocated
      into the nucleus of HeLa cells where it stimulates rRNA transcription. Thus,
      besides its angiogenic activity, angiogenin also plays a role in cancer cell
      proliferation.

PMID- 15735022
TI  - Mitotic infidelity and centrosome duplication errors in cells overexpressing
      tripeptidyl-peptidase II.
AB  - The oligopeptidase tripeptidyl-peptidase II (TPP II) is up-regulated Burkitt's
      lymphoma (BL) cells that overexpress the c-myc proto-oncogene and is required for
      their growth and survival. Here we show that overexpression of TPP II induces
      accelerated growth and resistance to apoptosis in human embryonic kidney 293
      cells. This correlates with the appearance of multiple chromosomal aberrations,
      numerical and structural centrosome abnormalities, and multipolar cell divisions.
      Similar mitotic aberrations were also observed in a panel of BL lines and were
      suppressed, in parallel with TPP II down-regulation, upon reversion of BL-like
      characteristics in EBV-immortalized B lymphocytes carrying a tetracycline
      regulated c-myc. Functional TPP II knockdown by small interfering RNA expression
      in BL cells caused the appearance of giant polynucleated cells that failed to
      complete cell division. Collectively, these data point to a role of TPP II in the
      regulation of centrosome homeostasis and mitotic fidelity suggesting that this
      enzyme may be a critical player in the induction and/or maintenance of genetic
      instability in malignant cells.

PMID- 15735023
TI  - Development of magnetic resonance imaging contrast material for in vivo mapping
      of tissue transglutaminase activity.
AB  - Transglutaminases are a family of enzymes that play an important role in tissue
      remodeling by catalyzing covalent cross-links between proteins of the
      extracellular matrix. Elevated activity of transglutaminase was shown at the
      boundaries of invading tumors, in association with angiogenesis, in stabilization
      of atherosclerotic plaques, and in generation of blood clots. The aim of this
      work was to develop a low molecular weight substrate of transglutaminase that
      could serve for noninvasive magnetic resonance and optical mapping of
      transglutaminase-mediated cross-linking activity. A 2 kDa contrast material was
      generated which showed cross-linking by either tissue transglutaminase or factor
      XIII in the context of multicellular tumor spheroids or fibrin clots,
      respectively. Successful detection by nuclear magnetic resonance microscopy of
      transglutaminase-mediated cross-linking of the contrast material to MCF7
      multicellular spheroids provides hope that this approach could potentially be
      developed for clinical demarcation of sites of transglutaminase activity.

PMID- 15735024
TI  - Visualizing chromosomes as transcriptome correlation maps: evidence of
      chromosomal domains containing co-expressed genes--a study of 130 invasive ductal
      breast carcinomas.
AB  - Completion of the working draft of the human genome has made it possible to
      analyze the expression of genes according to their position on the chromosomes.
      Here, we used a transcriptome data analysis approach involving for each gene the
      calculation of the correlation between its expression profile and those of its
      neighbors. We used the U133 Affymetrix transcriptome data set for a series of 130
      invasive ductal breast carcinomas to construct chromosomal maps of gene
      expression correlation (transcriptome correlation map). This highlighted
      nonrandom clusters of genes along the genome with correlated expression in
      tumors. Some of the gene clusters identified by this method probably arose
      because of genetic alterations, as most of the chromosomes with the highest
      percentage of correlated genes (1q, 8p, 8q, 16p, 16q, 17q, and 20q) were also the
      most frequent sites of genomic alterations in breast cancer. Our analysis showed
      that several known breast tumor amplicons (at 8p11-p12, 11q13, and 17q12) are
      located within clusters of genes with correlated expression. Using hierarchical
      clustering on samples and a Treeview representation of whole chromosome arms, we
      observed a higher-order organization of correlated genes, sometimes involving
      very large chromosomal domains that could extend to a whole chromosome arm.
      Transcription correlation maps are a new way of visualizing transcriptome data.
      They will help to identify new genes involved in tumor progression and new
      mechanisms of gene regulation in tumors.

PMID- 15735025
TI  - Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer
      cells.
AB  - ErbB1 and ErbB2 receptors are well-characterized targets for anticancer drugs,
      but the clinical relevance of the related ErbB4 receptor is unknown. Here, we
      have assessed the clinical significance of the proteolytically cleavable ErbB4
      isoforms in breast cancer patients and investigated their functions in vitro. The
      expression of transcripts encoding the cleavable ErbB4 isoforms associated with
      estrogen receptor-alpha (ER) expression (P < 0.001) and a high histologic grade
      of differentiation (P </= 0.002) in real-time reverse transcription-PCR analysis
      of 62 breast cancer samples. Despite high ErbB4 mRNA expression levels in a
      subset of samples, ErbB4 gene amplification was not observed. High ErbB4 protein
      expression levels, as assessed by immunohistochemistry, associated with a
      favorable outcome in ER-positive cases from a series of 458 breast cancer
      patients (P = 0.01), whereas no association between ErbB4 expression and survival
      was found among women with ER-negative cancer (P = 0.86). However, nuclear ErbB4
      immunoreactivity was associated with poor survival as compared with women whose
      cancer had membranous ErbB4 staining (P = 0.04). In vitro, overexpression of a
      cleavable ErbB4 isoform in ER-positive breast cancer cells resulted in
      translocation of a proteolytically released intracellular ErbB4 receptor fragment
      into the nucleus, as well as, enhanced proliferation, anchorage-independent
      growth, and estrogen response element-mediated transcriptional activity. These
      results suggest that the association of ErbB4 expression with clinical outcome is
      dependent on the subcellular localization of ErbB4 and that a proteinase
      cleavable ErbB4 isoform promotes growth of ER-positive breast cancer and enhances
      ER-mediated gene transcription.

PMID- 15735026
TI  - Development of skin tumors in mice transgenic for early genes of human
      papillomavirus type 8.
AB  - The cutaneous human papillomavirus (HPV) 8 is clearly involved in skin cancer
      development in epidermodysplasia verruciformis patients and its early genes E2,
      E6, and E7 have been implicated in cell transformation in vitro. To examine the
      functions of these genes in vivo we integrated the complete early region of HPV8
      into the genome of DBA/Bl6 mice. To target their expression to the basal layer of
      the squamous epithelia the transgenes were put under the control of the keratin
      14 promoter. Transgenic mice were back-crossed for up to six generations into
      both FVB/N and Bl6 mouse strains. Whereas none of the HPV8 transgene-negative
      littermates developed lesions in the skin or any other organ, 91% of HPV8
      transgenic mice developed single or multifocal benign tumors, characterized by
      papillomatosis, acanthosis, hyperkeratosis, and varying degrees of epidermal
      dysplasia. Squamous cell carcinomas developed in 6% of the transgenic FVB/N mice.
      Real-time reverse transcription-PCR showed highest expression levels for HPV8-E2,
      followed by E7 and E6. There was no consistent difference in relative viral RNA
      levels between healthy or dysplastic skin and malignant skin tumors. Whereas UV
      induced mutations in the tumor suppressor gene p53 are frequently detected in
      human skin carcinomas, mutations in p53 were not observed either in the benign or
      malignant mouse tumors. Nonmelanoma skin cancer developed in HPV8-transgenic mice
      without any treatment with physical or chemical carcinogens. This is the first
      experimental proof of the carcinogenic potential of an epidermodysplasia
      verruciformis-associated HPV-type in vivo.

PMID- 15735027
TI  - A mechanism-based antioxidant approach for the reduction of skin carcinogenesis.
AB  - Studies in our laboratories showed that overexpression of manganese superoxide
      dismutase (MnSOD) reduced tumor incidence in a multistage skin carcinogenesis
      mouse model. However, reduction of MnSOD by heterozygous knockout of the MnSOD
      gene (MnSOD KO) did not lead to an increase in tumor incidence, because a
      reduction of MnSOD enhanced both cell proliferation and apoptosis. The present
      study extends our previous studies in the MnSOD KO mice and shows that apoptosis
      in mouse epidermis occurred prior to cell proliferation (6 versus 24 hours) when
      treated with tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). To
      investigate the possibility that a timed administration of SOD following
      apoptosis but before proliferation may lead to suppression of tumor incidence, we
      applied a SOD mimetic (MnTE-2-PyP(5+)) 12 hours after each TPA treatment.
      Biochemical studies showed that MnTE-2-PyP(5+) suppressed the level of protein
      carbonyls and reduced the activity of activator protein-1 and the level of
      proliferating cellular nuclear antigen, without reducing the activity of p53 or
      DNA fragmentation following TPA treatment. Histologic examination confirmed that
      MnTE-2-PyP(5+) suppressed mitosis without interfering with apoptosis. Remarkably,
      the incidence and multiplicity of skin tumors were reduced in mice that received
      MnTE-2-PyP(5+) before cell proliferation. These results show a novel strategy for
      an antioxidant approach to cancer intervention.

PMID- 15735028
TI  - PTEN and hypoxia regulate tissue factor expression and plasma coagulation by
      glioblastoma.
AB  - We have previously proposed that intravascular thrombosis and subsequent
      vasoocclusion contribute to the development of pseudopalisading necrosis, a
      pathologic hallmark that distinguishes glioblastoma (WHO grade 4) from lower
      grade astrocytomas. To better understand the potential prothrombotic mechanisms
      underlying the formation of these structures that drive tumor angiogenesis, we
      investigated tissue factor (TF), a potent procoagulant protein known to be
      overexpressed in astrocytomas. We hypothesized that PTEN loss and tumor hypoxia,
      which characterize glioblastoma but not lower grade astrocytomas, could up
      regulate TF expression and cause intravascular thrombotic occlusion. We examined
      the effect of PTEN restoration and hypoxia on TF expression and plasma
      coagulation using a human glioma cell line containing an inducible wt-PTEN cDNA.
      Cell exposure to hypoxia (1% O(2)) markedly increased TF expression, whereas
      restoration of wt-PTEN caused decreased cellular TF. The latter effect was at
      least partially dependent on PTEN's protein phosphatase activity. Hypoxic cells
      accelerated plasma clotting in tilt tube assays and this effect was prevented by
      both inhibitory antibodies to TF and plasma lacking factor VII, implicating TF
      dependent mechanisms. To further examine the genetic events leading to TF up
      regulation during progression of astrocytomas, we investigated its expression in
      a series of human astrocytes sequentially infected with E6/E7/human telomerase,
      Ras, and Akt. Cells transformed with Akt showed the greatest incremental increase
      in hypoxia-induced TF expression and secretion. Together, our results show that
      PTEN loss and hypoxia up-regulate TF expression and promote plasma clotting by
      glioma cells, suggesting that these mechanisms may underlie intravascular
      thrombosis and pseudopalisading necrosis in glioblastoma.

PMID- 15735029
TI  - The homeobox gene Gax inhibits angiogenesis through inhibition of nuclear factor
      kappaB-dependent endothelial cell gene expression.
AB  - The growth and metastasis of tumors are heavily dependent on angiogenesis, but
      much of the transcriptional regulation of vascular endothelial cell gene
      expression responsible for angiogenesis remains to be elucidated. The homeobox
      gene Gax is expressed in vascular endothelial cells and inhibits proliferation
      and tube formation in vitro. We hypothesized that Gax is a negative
      transcriptional regulator of the endothelial cell angiogenic phenotype and
      studied its regulation and activity in vascular endothelial cells. Several
      proangiogenic factors caused a rapid down-regulation of Gax mRNA in human
      vascular endothelial cells, as did conditioned media from breast cancer cell
      lines. In addition, Gax expression using a replication-deficient adenoviral
      vector inhibited human umbilical vein endothelial cell migration toward
      proangiogenic factors in vitro and inhibited angiogenesis in vivo in Matrigel
      plugs. To identify putative downstream targets of Gax, we examined changes in
      global gene expression in endothelial cells due to Gax activity. Gax expression
      resulted in changes in global gene expression consistent with a quiescent,
      nonangiogenic phenotype, with increased expression of cyclin kinase inhibitors
      and decreased expression of genes implicated in endothelial cell activation and
      angiogenesis. Further analysis revealed that Gax down-regulated numerous nuclear
      factor-kappaB (NF-kappaB) target genes and decreased the binding of NF-kappaB to
      its target sequence in electrophoretic mobility shift assays. To our knowledge,
      Gax is the first homeobox gene described that inhibits NF-kappaB activity in
      vascular endothelial cells. Because NF-kappaB has been implicated in endothelial
      cell activation and angiogenesis, the down-regulation of NF-kappaB-dependent
      genes by Gax suggests one potential mechanism by which Gax inhibits the
      angiogenic phenotype.

PMID- 15735030
TI  - Characterizing extravascular fluid transport of macromolecules in the tumor
      interstitium by magnetic resonance imaging.
AB  - Noninvasive imaging techniques to image and characterize delivery and transport
      of macromolecules through the extracellular matrix (ECM) and supporting stroma of
      a tumor are necessary to develop treatments that alter the porosity and integrity
      of the ECM for improved delivery of therapeutic agents and to understand factors
      which influence and control delivery, movement, and clearance of macromolecules.
      In this study, a noninvasive imaging technique was developed to characterize the
      delivery as well as interstitial transport of a macromolecular agent, albumin
      GdDTPA, in the MCF-7 human breast cancer model in vivo, using magnetic resonance
      imaging. The transport parameters derived included vascular volume, permeability
      surface area product, macromolecular fluid exudate volume, and drainage and
      pooling rates. Immunohistochemical staining for the lymphatic endothelial marker
      LYVE-1 was done to determine the contribution of lymphatics to the macromolecular
      drainage. Distinct pooling and draining regions were detected in the tumors using
      magnetic resonance imaging. A few lymphatic vessels positively stained for LYVE-1
      were also detected although these were primarily collapsed and tenuous suggesting
      that lymphatic drainage played a minimal role, and that the bulk of drainage was
      due to convective transport through the ECM in this tumor model.

PMID- 15735031
TI  - Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis
      of human breast cancer cells.
AB  - Chemotaxis plays an important role in cancer cell metastasis. In this study, we
      showed that epidermal growth factor (EGF) was a more potent chemoattractant than
      chemokine SDF-1alpha/CXCL12 for human breast cancer cell MDA-MB-231. Different
      inhibitors were used to evaluate the involvement of 12 protein kinase C (PKC)
      isotypes in the chemotactic signaling pathway. Chelerythrine chloride, an
      inhibitor of all PKC isotypes, blocked chemotaxis, whereas inhibitors of classic
      and novel PKC, such as Go6976, Go6850, or calphostin C, only impaired EGF-induced
      chemotaxis to a minor extent by not greater-than32% inhibition. These data
      suggested that atypical PKC were involved. The ligand-induced actin
      polymerization and cell adhesion were also similarly dependent on atypical PKC.
      Immunofluorescent staining showed an EGF-induced, LY294002-sensitive
      translocation of PKCzeta from the cytosol to the plasma membrane, indicating that
      EGF was capable of activating PKCzeta, probably via phosphoinositide 3 kinases. A
      myristoylated PKCzeta pseudosubstrate blocked the chemotaxis with an IC(50) of 20
      mumol/L. To expand our investigation, we further showed that in MCF-7 and T47D,
      two additional human breast cancer cell lines, EGF-activated PKCzeta and the
      PKCzeta pseudosubstrate, inhibited chemotaxis. Taken together, our data suggest
      that PKCzeta is an essential component of the EGF-stimulated chemotactic
      signaling pathway in human breast cancer cells.

PMID- 15735032
TI  - Leukemic stem cells in childhood high-risk ALL/t(9;22) and t(4;11) are present in
      primitive lymphoid-restricted CD34+CD19- cells.
AB  - Open questions in the pathogenesis of childhood acute lymphoblastic leukemia
      (ALL) are which hematopoietic cell is target of the malignant transformation and
      whether primitive stem cells contribute to the leukemic clone. Although good
      prognosis ALL is thought to originate in a lymphoid progenitor, it is unclear if
      this applies to high-risk ALL. Therefore, immature CD34(+)CD19(-) bone marrow
      cells from 8 children with ALL/t(9;22) and 12 with ALL/t(4;11) were purified and
      analyzed by fluorescence in situ hybridization, reverse transcription-PCR (RT
      PCR), and colony assays. Fifty-six percent (n = 8, SD 31%) and 68% (n = 12, SD
      26%) of CD34(+)CD19(-) cells in ALL/t(9;22) and ALL/t(4;11), respectively,
      carried the translocation. In addition, 5 of 168 (3%) and 22 of 228 (10%)
      myeloerythroid colonies expressed BCR/ABL and MLL/AF4. RT-PCR results were
      confirmed by sequence analysis. Interestingly, in some patients with ALL/t(4;11),
      alternative splicing was seen in myeloid progenitors compared with the bulk
      leukemic population, suggesting that these myeloid colonies might be part of the
      leukemic cell clone. Fluorescence in situ hybridization analysis, however, shows
      that none of these myeloid colonies (0 of 41 RT-PCR-positive colonies) originated
      from a progenitor cell that carries the leukemia-specific translocation. Thus,
      leukemic, translocation-positive CD34(+)CD19(-) progenitor/stem cells that were
      copurified by cell sorting were able to survive in these colony assays for up to
      28 days allowing amplification of the respective fusion transcripts by sensitive
      RT-PCR. In conclusion, we show that childhood high-risk ALL/t(9;22) and t(4;11)
      originate in a primitive CD34(+)CD19(-) progenitor/stem cell without a
      myeloerythroid developmental potential.

PMID- 15735033
TI  - Mitotic arrest deficient 2 expression induces chemosensitization to a DNA
      damaging agent, cisplatin, in nasopharyngeal carcinoma cells.
AB  - Recently, mitotic arrest deficient 2 (MAD2)-mediated spindle checkpoint is shown
      to induce mitotic arrest in response to DNA damage, indicating overlapping roles
      of the spindle checkpoint and DNA damage checkpoint. In this study, we
      investigated if MAD2 played a part in cellular sensitivity to DNA-damaging
      agents, especially cisplatin, and whether it was regulated through mitotic
      checkpoint. Using nine nasopharyngeal carcinoma (NPC) cell lines, we found that
      decreased MAD2 expression was correlated with cellular resistance to cisplatin
      compared with the cell lines with high levels of MAD2. Exogenous MAD2 expression
      in NPC cells also conferred sensitivity to DNA-damaging agents especially
      cisplatin but not other anticancer drugs with different mechanisms of action. The
      increased cisplatin sensitivity in MAD2 transfectants was associated with mitotic
      arrest and activation of apoptosis pathway evidenced by the increased mitotic
      index and apoptosis rate as well as decreased Bcl-2 and Bax ratio and expression
      of cleaved poly(ADP-ribose) polymerase and caspase 3. Our results indicate that
      the MAD2-induced chemosensitization to cisplatin in NPC cells is mediated through
      the induction of mitotic arrest, which in turn activates the apoptosis pathway.
      Our evidence further confirms the previous hypothesis that spindle checkpoint
      plays an important part in DNA damage-induced cell cycle arrest and suggests a
      novel role of MAD2 in cellular sensitivity to cisplatin.

PMID- 15735034
TI  - Combined targeting of the estrogen receptor and the epidermal growth factor
      receptor in non-small cell lung cancer shows enhanced antiproliferative effects.
AB  - Identifying new effective therapeutic treatments for lung cancer is critical to
      improving overall patient survival. We have targeted both the estrogen receptor
      (ER) and the epidermal growth factor receptor (EGFR) pathways using an ER
      antagonist, fulvestrant ("Faslodex"), and the selective EGFR tyrosine kinase
      inhibitor, gefitinib ("Iressa"), in non-small cell lung cancer (NSCLC) cells.
      Rapid activation of phospho-EGFR and phospho-p44/p42 mitogen-activated protein
      kinase by estrogen was observed, indicating nonnuclear ER transactivation of
      EGFR. Additionally, EGFR protein expression was down-regulated in response to
      estrogen and up-regulated in response to fulvestrant in vitro, suggesting that
      the EGFR pathway is activated when estrogen is depleted in NSCLC cells. Cell
      growth and apoptosis were examined in several NSCLC lines that express varying
      amounts of ERbeta, EGFR, and Neu but no full-length ERalpha. One cell line
      contained an EGFR mutation. Cells were exposed to 10 nmol/L estrogen and 10 ng/mL
      EGF and either 1 mumol/L fulvestrant or 1 mumol/L gefitinib alone or in
      combination. In all cell lines, the drug combination decreased cell proliferation
      up to 90% and increased apoptosis 2-fold. The relative responses to gefitinib and
      fulvestrant were similar regardless of ER and EGFR expression and mutation
      status. In an in vivo lung tumor xenograft model, the drug combination decreased
      tumor volume in severe combined immunodeficient mice by approximately 60%
      compared with 49% and 32% for gefitinib and fulvestrant treatment alone,
      respectively. Antitumor effects of the combination therapy were accompanied by
      biochemical and histologic evidence of increased apoptosis, decreased phospho
      p44/p42 mitogen-activated protein kinase expression, and increased Ki-67
      expression compared with individual treatment. These studies provide evidence of
      a functional interaction between the ER and the EGFR pathways in NSCLC.

PMID- 15735035
TI  - Quantitative immuno-positron emission tomography imaging of HER2-positive tumor
      xenografts with an iodine-124 labeled anti-HER2 diabody.
AB  - Positron emission tomography (PET) provides an effective means of both
      diagnosing/staging several types of cancer and evaluating efficacy of treatment.
      To date, the only U.S. Food and Drug Administration-approved radiotracer for
      oncologic PET is (18)F-fluoro-deoxyglucose, which measures glucose accumulation
      as a surrogate for malignant activity. Engineered antibody fragments have been
      developed with the appropriate targeting specificity and systemic elimination
      properties predicted to allow for effective imaging of cancer based on expression
      of tumor associated antigens. We evaluated a small engineered antibody fragment
      specific for the HER2 receptor tyrosine kinase (C6.5 diabody) for its ability to
      function as a PET radiotracer when labeled with iodine-124. Our studies revealed
      HER2-dependent imaging of mouse tumor xenografts with a time-dependent increase
      in tumor-to-background signal over the course of the experiments. Radioiodination
      via an indirect method attenuated uptake of radioiodine in tissues that express
      the Na/I symporter without affecting the ability to image the tumor xenografts.
      In addition, we validated a method for using a clinical PET/computed tomography
      scanner to quantify tumor uptake in small-animal model systems; quantitation of
      the tumor targeting by PET correlated with traditional necropsy-based analysis at
      all time points analyzed. Thus, diabodies may represent an effective molecular
      structure for development of novel PET radiotracers.

PMID- 15735036
TI  - Functional expression and mutations of c-Met and its therapeutic inhibition with
      SU11274 and small interfering RNA in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is a difficult disease to treat. The c-Met
      receptor is an attractive potential target for novel therapeutic inhibition in
      human cancers. We provide strong evidence that c-Met is overexpressed, activated,
      and sometimes mutated in NSCLC cell lines and tumor tissues. Expression of c-Met
      was found in all (100%) of the NSCLC tumor tissues examined (n = 23) and most
      (89%) of the cell lines (n = 9). Sixty-one percent of tumor tissues strongly
      expressed total c-Met, especially adenocarcinoma (67%). Specific expression of
      phospho-Met (p-Met) [Y1003] and [Y1230/1234/1235] was seen by
      immunohistochemistry. p-Met expression was preferentially observed at the NSCLC
      tumor invasive fronts. c-Met alterations were identified within the semaphorin
      domain (E168D, L299F, S323G, and N375S) and the juxtamembrane domain (R988C,
      R988C + T1010I, S1058P, and alternative splice product skipping entire
      juxtamembrane domain) of a NSCLC cell line and adenocarcinoma tissues. We
      validated c-Met as potential therapeutic target using small interfering RNA down
      regulation of the receptor expression by 50% to 60% in NSCLC cells. This led to
      inhibition of p-Met and phospho-AKT and up to 57.1 +/- 7.2% cell viability
      inhibition at 72 hours. The selective small molecule inhibitor of c-Met SU11274
      inhibited cell viability in c-Met-expressing NSCLC cells. SU11274 also abrogated
      hepatocyte growth factor-induced phosphorylation of c-Met and its downstream
      signaling. Here, we provide first direct evidence by small interfering RNA
      targeting and small molecule inhibitor that c-Met is important in NSCLC biology
      and biochemistry. These results indicate that c-Met inhibition will be an
      important therapeutic strategy against NSCLC to improve its clinical outcome.

PMID- 15735037
TI  - The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent
      with telomere targeting and interference with telomerase function.
AB  - Interference with telomerase and telomere maintenance is emerging as an
      attractive target for anticancer therapies. Ligand-induced stabilization of G
      quadruplex formation by the telomeric DNA single-stranded 3' overhang inhibits
      telomerase from catalyzing telomeric DNA synthesis and from capping telomeric
      ends. We report here the effects of a 3,6,9-trisubstituted acridine compound,
      BRACO-19, on telomerase function in vitro and in vivo. The biological activity of
      BRACO-19 was evaluated in the human uterus carcinoma cell line UXF1138L, which
      has very short telomeres (2.7 kb). In vitro, nuclear human telomerase reverse
      transcriptase (hTERT) expression was drastically decreased after 24 hours,
      induction of cellular senescence and complete cessation of growth was seen after
      15 days, paralleled by telomere shortening of ca. 0.4 kb. In vivo, BRACO-19 was
      highly active as a single agent against early-stage (68 mm(3)) tumors in a s.c.
      growing xenograft model established from UXF1138L cells, if given chronically at
      2 mg per kg per day i.p. BRACO-19 produced growth inhibition of 96% compared with
      controls accompanied by partial regressions (P < 0.018). Immunostaining of
      xenograft tissues showed that this response was paralleled by loss of nuclear
      hTERT protein expression and an increase in atypical mitoses indicative of
      telomere dysfunction. Cytoplasmic hTERT expression and its colocalization with
      ubiquitin was observed suggesting that hTERT is bound to ubiquitin and targeted
      for enhanced degradation upon BRACO-19 treatment. This is in accord with a model
      of induced displacement of telomerase from the telomere. The in vitro and in vivo
      data presented here is consistent with the G-quadruplex binding ligand BRACO-19
      producing an anticancer effect by inhibiting the capping and catalytic functions
      of telomerase.

PMID- 15735038
TI  - Inhibition of integrin-linked kinase by a selective small molecule inhibitor,
      QLT0254, inhibits the PI3K/PKB/mTOR, Stat3, and FKHR pathways and tumor growth,
      and enhances gemcitabine-induced apoptosis in human orthotopic primary pancreatic
      cancer xenografts.
AB  - Integrin-linked kinase (ILK) couples integrins and growth factors to downstream
      signaling pathways involving phosphatidylinositol 3-kinase, protein kinase B/Akt
      (PKB/Akt), and glycogen synthase kinase-3beta. The anticancer effects of ILK
      inhibitor QLT0254 were tested in an orthotopic primary xenograft model of
      pancreatic cancer. The pharmacodynamic effects of a single dose of QLT0254 on the
      phosphorylation of PKB/Akt were measured by immunohistochemistry and Western
      blotting, and showed a decrease of >80% after 2 hours, followed by recovery over
      24 hours, consistent with the pharmacokinetic profile of this compound in mice.
      There was also suppression in phosphorylated PKB Thr(308), forkhead in
      rhabdomyosarcoma, S6K1, S6, 4E-BP1, and signal transducers and activators of
      transcription 3 Tyr(705) and Ser(727) protein levels with ILK inhibition by
      QLT0254. However, we did not observe an effect on phosphoinositide-dependent
      kinase 1, glycogen synthase kinase-3beta, and extracellular signal-regulated
      kinase phosphorylation or on total PKB and ILK protein expression levels with
      QLT0254 treatment. In tumor growth inhibition experiments, daily treatment with
      QLT0254 for 3 weeks was well tolerated and produced significant tumor growth
      inhibition compared with vehicle control (P = 0.001). When a single dose of
      QLT0254 and chemotherapy agent gemcitabine was administered, there was a
      significant 5.4-fold increase in acute apoptosis in the combination therapy group
      compared with vehicle controls (P = 0.002). However, the acute effects of QLT0254
      on proliferation were not statistically significant. These results show in vivo
      evidence that ILK plays a prominent role in oncogenic phosphatidylinositol 3
      kinase/PKB signaling in vivo with major impact on the mammalian target of
      rapamycin, signal transducers and activators of transcription 3, and forkhead in
      rhadomyosarcoma signaling pathways, suggesting that ILK inhibitors might show
      activity in pancreatic cancer patients.

PMID- 15735039
TI  - Histone deacetylase inhibitor valproic acid enhances the cytokine-induced
      expansion of human hematopoietic stem cells.
AB  - Ex vivo amplification of human hematopoietic stem cells (HSC) without loss of
      their self-renewing potential represents an important target for transplantation,
      gene and cellular therapies. Valproic acid is a safe and widely used neurologic
      agent that acts as a potent inhibitor of histone deacetylase activities. Here, we
      show that valproic acid addition to liquid cultures of human CD34+ cells isolated
      from cord blood, mobilized peripheral blood, and bone marrow strongly enhances
      the ex vivo expansion potential of different cytokine cocktails as shown by
      morphologic, cytochemical, immunophenotypical, clonogenic, and gene expression
      analyses. Notably, valproic acid highly preserves the CD34 positivity after 1
      week (range, 40-89%) or 3 weeks (range, 21-52%) amplification cultures with two
      (Flt3L + thrombopoietin) or four cytokines (Flt3L + thrombopoietin + stem cell
      factor + interleukin 3). Moreover, valproic acid treatment increases histone H4
      acetylation levels at specific regulatory sites on HOXB4, a transcription factor
      gene with a key role in the regulation of HSC self-renewal and AC133, a
      recognized marker gene for stem cell populations. Overall, our results relate the
      changes induced by valproic acid on chromatin accessibility with the enhancement
      of the cytokine effect on the maintenance and expansion of a primitive
      hematopoietic stem cell population. These findings underscore the potentiality of
      novel epigenetic approaches to modify HSC fate in vitro.

PMID- 15735041
TI  - Virus-associated RNA I-deleted adenovirus, a potential oncolytic agent targeting
      EBV-associated tumors.
AB  - Given the growing number of tumor types recognizably associated with EBV
      infection, it is critically important that therapeutic strategies are developed
      to treat such tumors. Replication-selective oncolytic adenoviruses represent a
      promising new platform for anticancer therapy. Virus-associated I (VAI) RNAs of
      adenoviruses are required for efficient translation of viral mRNAs. When the VAI
      gene is deleted, adenovirus replication is impeded in most cells (including HEK
      293 cells). EBV-encoded small RNA1 is uniformly expressed in most EBV-associated
      human tumors and can functionally substitute for the VAI RNAs of adenovirus. It
      enables replication to proceed through complementation of VAI-deletion mutants.
      We hypothesized that VAI-deleted adenovirus would selectively replicate in EBV
      positive tumor cells due to the presence of EBV-encoded small RNA1 with no (or
      poor) replication in normal or EBV-negative tumor cells. In this report, we show
      that high levels of replication occurred in the VAI-deleted mutant in the EBV
      positive tumor cells compared with low (or negligible) levels in EBV-negative and
      normal human primary cells. Correspondingly, high toxicity levels were observed
      in EBV-positive tumor cells but not in EBV-negative tumor or normal human primary
      cells. In vivo, VAI-deleted adenovirus showed superior antitumoral efficacy to
      wild-type adenovirus in EBV-positive tumor xenografts, with lower hepatotoxicity
      than wild-type adenovirus. Our data suggest that VAI-deleted adenovirus is a
      promising replication-selective oncolytic virus with targeting specificity for
      EBV-associated tumors.

PMID- 15735040
TI  - Inhibitory anti-FLT3 antibodies are capable of mediating antibody-dependent cell
      mediated cytotoxicity and reducing engraftment of acute myelogenous leukemia
      blasts in nonobese diabetic/severe combined immunodeficient mice.
AB  - Aberrant FLT3 expression and/or mutation plays a significant role in
      leukemogenesis. This has prompted the development of selective small molecule
      tyrosine kinase inhibitors against FLT3. However, like most tyrosine kinase
      inhibitors, those against FLT3 are not completely specific and at the doses
      required to completely inhibit target, significant toxicities may occur. In
      addition, tyrosine kinase inhibitors for other kinases have been shown to select
      for cells that become resistant. To overcome some of these limitations we
      developed two fully human phage display monoclonal antibodies against FLT3 (IMC
      EB10 and IMC-NC7). These antibodies inhibited ligand-mediated activation of wild
      type FLT3 and constitutively activated mutant FLT3 and in most cell types
      affected downstream STAT5, AKT, and mitogen-activated protein kinase activation.
      In addition to interfering with FLT3 signaling, IMC-EB10 and, to a significantly
      lesser extent, IMC-NC7 initiated antibody-dependent cell-mediated cytotoxicity on
      FLT3-expressing cells. When IMC-EB10 was used in vivo to treat nonobese
      diabetic/severe combined immunodeficient mice given injections of primary
      FLT3/ITD acute myelogenous leukemia samples or myeloid cell lines with FLT3
      expression, it significantly decreased engraftment of leukemic cells and
      increased survival, respectively. In contrast, IMC-EB10 treatment did not reduce
      engraftment of normal human CD34+ cord blood cells nor did it show any
      significant inhibition of normal murine hematopoiesis. Thus, these types of
      antibodies have the potential to be safe and effective new therapeutic agents for
      acute myelogenous leukemia and possibly other FLT3-expressing malignancies.

PMID- 15735042
TI  - Oncolytic herpes simplex virus vector therapy of breast cancer in C3(1)/SV40 T
      antigen transgenic mice.
AB  - Oncolytic herpes simplex virus vectors are a promising strategy for cancer
      therapy, as direct cytotoxic agents, inducers of antitumor immune responses, and
      as expressers of anticancer genes. Progress is dependent upon representative
      preclinical models to evaluate therapy. In this study, two families of oncolytic
      herpes simplex virus vectors (G207 and NV1020 series) that have been in clinical
      trials were examined for the treatment of breast cancer, using the C3(1)/T-Ag
      transgenic mouse model. Female mice spontaneously develop mammary carcinomas, and
      the C3(1)/T-Ag-derived tumor cell line M6c forms implantable tumors. Both in
      vitro and in vivo, G47Delta, derived from G207 by deletion of ICP47 and the US11
      promoter, was more efficacious than G207. Whereas NV1023, derived from NV1020 by
      deletion of ICP47 and insertion of LacZ, was as cytotoxic to M6c cells in vitro
      as G47Delta, it did not inhibit the growth of s.c. M6c tumors but did extend the
      survival of intracerebral tumor bearing mice. In contrast, NV1042, NV1023
      expressing interleukin 12, inhibited s.c. M6c tumor growth to a similar extent as
      G47Delta, but was less effective than NV1023 in intracerebral tumors. In the
      spontaneously arising mammary tumor model, when only the first arising tumor per
      mouse was treated, G47Delta inhibited the growth of a subset of tumors, and when
      all tumors were treated, G47Delta significantly delayed tumor progression. When
      the first mammary tumor was treated and the remaining mammary glands removed,
      NV1042 was more efficacious than G47Delta at inhibiting the growth and
      progression of injected tumors.

PMID- 15735043
TI  - Gefitinib ("Iressa", ZD1839), an epidermal growth factor receptor tyrosine kinase
      inhibitor, reverses breast cancer resistance protein/ABCG2-mediated drug
      resistance.
AB  - Gefitinib ("Iressa", ZD1839) is an orally active, selective epidermal growth
      factor receptor tyrosine kinase inhibitor, and the single agent is clinically
      effective in non-small cell lung cancer. Although gefitinib combined with various
      cytotoxic agents has been reported to enhance cytotoxicity in vitro and in mouse
      models, the mechanism remains undetermined. Here, to explore the mechanism with
      topoisomerase I inhibitors, we focused on the efflux pump of the breast cancer
      resistance protein (BCRP/ABCG2), and then examined whether gefitinib restored
      drug sensitivity in multidrug-resistant cancer cells overexpressing BCRP. We used
      PC-6 human small cell lung cancer cells and multidrug-resistant PC-6/SN2-5H cells
      selected with SN-38 of the active metabolite of irinotecan, and BCRP
      overexpressing MCF-7/MX cells selected with mitoxantrone and BCRP cDNA
      transfectant MCF-7/clone 8 cells. Drug sensitivity against anticancer drugs was
      determined by tetrazolium dye assay, and intracellular topotecan accumulation by
      FACScan. The topotecan transport study was done using the plasma membrane
      vesicles of PC-6/SN2-5H cells. The resistant PC-6/SN2-5H cells overexpressed BCRP
      but not epidermal growth factor receptor mRNA. Ten micromoles of gefitinib
      reversed topotecan, SN-38, and mitoxantrone resistance, and increased the
      intracellular topotecan accumulation in the resistant cells but not in the
      parental cells. Furthermore, gefitinib inhibited the topotecan transport into the
      vesicles, and the K(i) value was 1.01 +/- 0.09 micromol/L in the Dixon plot
      analysis, indicating direct inhibition of BCRP by gefitinib. However, gefitinib
      was not transported into the vesicles with the high-performance liquid
      chromatography method. These results indicate that gefitinib reverses BCRP
      mediated drug resistance by direct inhibition other than competitive inhibition
      as a BCRP substrate. Combination of gefitinib and topoisomerase I inhibitors
      could be clinically effective in cancers expressing BCRP.

PMID- 15735044
TI  - Induction of apoptosis in primary meningioma cultures by fenretinide.
AB  - Fenretinide, a synthetic retinoid that induces apoptosis in tumor cells in vitro,
      is being evaluated in clinical trials as a chemotherapeutic agent against several
      malignancies. Due to its ease of administration, long-term tolerability, and low
      incidence of long-term side effects, we explored its potential as a therapeutic
      agent against meningiomas by examining its efficacy in vitro against such cells
      in primary culture. Cells, cultured from freshly resected benign, atypical, or
      malignant meningiomas, were exposed to fenretinide (10 mumol/L). Treatment
      effects were assessed using flow cytometry, Western blot analysis,
      semiquantitative reverse transcription-PCR for retinoid receptor expression, and
      changes in insulin-like growth factor-I (IGF-I)-induced proliferation.
      Fenretinide induced apoptosis in the three grades of meningioma primary cells
      tested, as shown by the appearance of a sub-G(1) fraction in flow cytometric
      analysis and by the detection of poly-adenosyl ribonucleotidyl phosphorylase
      cleavage indicating caspase activation. Fenretinide treatment also increased
      levels of the death receptor DR5 and caused mitochondrial membrane
      depolarization. The levels of the retinoid receptors, retinoic acid receptor
      alpha and retinoid X receptor gamma, were up-regulated in response to
      fenretinide, suggestive of ligand-induced receptor up-regulation. IGF-I-induced
      proliferation in the meningioma cells was abolished by fenretinide. We conclude
      that fenretinide induces apoptosis in all three histologic subtypes of meningioma
      and exerts diverse cellular effects, including DR5 up-regulation, modulation of
      retinoid receptor levels, and inhibition of IGF-I-induced proliferation. These
      results provide preliminary evidence that fenretinide has activity against
      meningiomas and suggest that further studies are warranted to explore its
      potential as a therapeutic agent against meningiomas.

PMID- 15735045
TI  - Expression profiling of homocysteine junction enzymes in the NCI60 panel of human
      cancer cell lines.
AB  - Methionine metabolism provides two key cellular reagents: S-adenosylmethionine
      and glutathione, derived from the common intermediate, homocysteine. A majority
      of cancer cells exhibit a methionine-dependent phenotype whereby they are unable
      to grow in medium in which methionine is replaced by its precursor, homocysteine.
      Additionally, CpG island hypermethylation of tumor suppressor gene promoters is
      observed in a background of global hypomethylation in cancerous cells. In this
      study, we have profiled the expression levels of the homocysteine junction
      enzymes, methionine synthase (MS), MS reductase (MSR), and cystathionine beta
      synthase (CBS) in the NCI60 panel of cancer cell lines. The doubling time of non
      small lung cell cancer lines, which exhibit the lowest levels of MS within the
      panel, was significantly correlated with expression of MS. The ratio of MS to MSR
      varied over a 5-fold range in the different cell types, which may modulate
      methionine synthesis. Interestingly, markedly reduced CBS expression was seen in
      the methionine-dependent prostate cancer cell line, PC-3, but not in the
      methionine-independent cell line, DU-145. However, neither provision of the
      transsulfuration pathway product, cysteine, nor overexpression of CBS rescued the
      growth impairment, indicating that reduced CBS was not responsible for the
      methionine-dependent phenotype in this cell line.

PMID- 15735046
TI  - Thiazolidenediones mediate apoptosis in prostate cancer cells in part through
      inhibition of Bcl-xL/Bcl-2 functions independently of PPARgamma.
AB  - Certain members of the thiazolidenedione family of the peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists, such as troglitazone and
      ciglitazone, exhibit antitumor effects; however, the underlying mechanism remains
      inconclusive. This study shows that the effect of these thiazolidenedione members
      on apoptosis in prostate cancer cells is independent of PPARgamma activation.
      First, close structural analogues of thiazolidenediones, whereas devoid of
      PPARgamma activity, retain the ability to induce apoptosis with equal potency.
      Second, both PC-3 (PPARgamma-expressing) and LNCaP (PPARgamma-deficient) cells
      are sensitive to apoptosis induction by troglitazone and its PPARgamma-inactive
      analogue irrespective of their PPARgamma expression status. Third, rosiglitazone
      and pioglitazone, potent PPARgamma agonists, show marginal effects on apoptosis
      even at high concentrations. Evidence indicates that the apoptotic effect of
      troglitazone, ciglitazone, and their PPARgamma-inactive analogues 5-[4-(6-hydroxy
      2,5,7,8-tetramethyl-chroman-2-ylmethoxy)-benzylidene]-2,4-thiazolidine-dione
      (Delta2-TG) and 5-[4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4
      dione, respectively, is in part attributable to their ability to inhibit the anti
      apoptotic functions of Bcl-xL and Bcl-2. Treatment of PC-3 cells with
      troglitazone or Delta2-TG led to reduced association of Bcl-2 and Bcl-xL with
      Bak, leading to caspase-dependent apoptosis. Bcl-xL overexpression protects LNCaP
      cells from apoptosis induction by troglitazone and Delta2-TG in an expression
      level-dependent manner. Considering the pivotal role of Bcl-xL/Bcl-2 in
      regulating mitochondrial integrity, this new mode of mechanism provides a
      framework to account for the PPARgamma-independent action of thiazolidenediones
      in inducing apoptosis in cancer cells. Moreover, dissociation of these two
      pharmacologic activities provides a molecular basis to develop novel Bcl-xL/Bcl-2
      inhibitors, of which the proof of principle is illustrated by a Delta2-TG
      analogue with potent in vivo antitumor activities.

PMID- 15735047
TI  - Simultaneous generation of CD8+ and CD4+ melanoma-reactive T cells by retroviral
      mediated transfer of a single T-cell receptor.
AB  - Adoptive immunotherapy of cancer requires the generation of large numbers of
      tumor antigen-reactive T cells for transfer into cancer patients. Genes encoding
      tumor antigen-specific T-cell receptors can be introduced into primary human T
      cells by retroviral mediated gene transfer as a potential method of providing any
      patient with a source of autologous tumor-reactive T cells. A T-cell receptor
      specific for a class I MHC (HLA-A2)-restricted epitope of the melanoma antigen
      tyrosinase was isolated from a CD4(+) tumor-infiltrating lymphocyte (TIL 1383I)
      and introduced into normal human peripheral blood lymphocytes by retroviral
      transduction. T-cell receptor-transduced T cells secreted various cytokines when
      cocultured with tyrosinase peptide-loaded antigen-presenting cells as well as
      melanoma cells in an HLA-A2-restricted manner, and could also lyse target cells.
      Furthermore, T-cell clones isolated from these cultures showed both CD8(+) and
      CD4(+) transduced T cells could recognize HLA-A2(+) melanoma cells, giving us the
      possibility of engineering class I MHC-restricted effector and T helper cells
      against melanoma. The ability to confer class I MHC-restricted tumor cell
      recognition to CD4(+) T cells makes the TIL 1383I TCR an attractive candidate for
      T-cell receptor gene transfer-based immunotherapy.

PMID- 15735048
TI  - Functional characterization of EBV-encoded nuclear antigen 1-specific CD4+ helper
      and regulatory T cells elicited by in vitro peptide stimulation.
AB  - CD4(+) helper and regulatory T (Treg) cells play important but opposing roles in
      regulating host immune responses against cancer and other diseases. However, very
      little is known about the antigen specificity of CD4(+) Treg cells. Here we
      describe the generation of a panel of EBV-encoded nuclear antigen 1 (EBNA1)
      specific CD4(+) T-cell lines and clones that recognize naturally processed EBNA1
      P(607-619) and -P(561-573) peptides in the context of HLA-DQ2 and HLA-DR11, 
      DR12, and -DR13 molecules, respectively. Phenotypic and functional analyses of
      these CD4(+) T cells revealed that they represent EBNA1-specific CD4(+) T helper
      as well as Treg cells. CD4(+) Treg cells do not secrete interleukin (IL)-10 and
      transforming growth factor beta cytokines but express CD25, the glucocorticoid
      induced tumor necrosis factor receptor-related protein (GITR), and Forkhead Box
      P3 (Foxp3), and are capable of suppressing the proliferative responses of naive
      CD4(+) and CD8(+) T cells to stimulation with mitogenic anti-CD3 antibody. The
      suppressive activity of these CD4(+) Treg cells is mediated via cell-cell contact
      or in part by a cytokine-dependent manner. Importantly, these Treg cells suppress
      IL-2 secretion by CD4(+) effector T cells specific for either EBNA1 or a melanoma
      antigen, suggesting that these CD4(+) Treg cells induce immune suppression. These
      observations suggest that the success of peptide-based vaccines against EBV
      associated cancer and other diseases may likely depend upon our ability to
      identify antigens/peptides that preferentially activate helper T cells and/or to
      design strategies to regulate the balance between CD4(+) helper and Treg cells.

PMID- 15735049
TI  - Gene expression profile of papillary thyroid cancer: sources of variability and
      diagnostic implications.
AB  - The study looked for an optimal set of genes differentiating between papillary
      thyroid cancer (PTC) and normal thyroid tissue and assessed the sources of
      variability in gene expression profiles. The analysis was done by oligonucleotide
      microarrays (GeneChip HG-U133A) in 50 tissue samples taken intraoperatively from
      33 patients (23 PTC patients and 10 patients with other thyroid disease). In the
      initial group of 16 PTC and 16 normal samples, we assessed the sources of
      variability in the gene expression profile by singular value decomposition which
      specified three major patterns of variability. The first and the most distinct
      mode grouped transcripts differentiating between tumor and normal tissues. Two
      consecutive modes contained a large proportion of immunity-related genes. To
      generate a multigene classifier for tumor-normal difference, we used support
      vector machines-based technique (recursive feature replacement). It included the
      following 19 genes: DPP4, GJB3, ST14, SERPINA1, LRP4, MET, EVA1, SPUVE, LGALS3,
      HBB, MKRN2, MRC2, IGSF1, KIAA0830, RXRG, P4HA2, CDH3, IL13RA1, and MTMR4, and
      correctly discriminated 17 of 18 additional PTC/normal thyroid samples and all 16
      samples published in a previous microarray study. Selected novel genes (LRP4,
      EVA1, TMPRSS4, QPCT, and SLC34A2) were confirmed by Q-PCR. Our results prove that
      the gene expression signal of PTC is easily detectable even when cancer cells do
      not prevail over tumor stroma. We indicate and separate the confounding
      variability related to the immune response. Finally, we propose a potent
      molecular classifier able to discriminate between PTC and nonmalignant thyroid in
      more than 90% of investigated samples.

PMID- 15735050
TI  - Regulation of endogenous gene expression in human non-small cell lung cancer
      cells by estrogen receptor ligands.
AB  - Estrogen receptor (ER) agonists and antagonists elicit distinct responses in non
      small cell lung cancer (NSCLC) cells. To determine how such responses are
      generated, the expression of ERalpha, ERbeta, and ER coregulators in human lung
      fibroblasts and human NSCLC cell lines was evaluated by immunoblot. Ligand
      dependent estrogenic responses in NSCLC cells are probably generated via ERbeta
      and the p160 coactivator GRIP1/TIF2, because expression of these proteins was
      detected, but not full-length ERalpha or the p160 coactivator SRC-1. ERbeta and
      GRIP1/TIF2 are shown to interact in vitro in a ligand-dependent manner and thus
      may form functional transcription complexes in NSCLC cells. Furthermore, the
      capacity of ER ligands to regulate gene expression in NSCLC cells was explored
      using gene miniarrays. Expression profiles were examined after treatment with ER
      agonist 17-beta-estradiol (E2), the pure ER antagonist ICI 182,780 (fulvestrant,
      Faslodex), or epidermal growth factor, which served as a positive control for an
      alternative growth stimulus. E-cadherin and inhibitor of differentiation 2 were
      differentially regulated by E2 versus ICI 182,780 in 201T and 273T NSCLC cell
      lines. Epidermal growth factor also stimulated proliferation of these cells but
      had no effect on expression of E-cadherin and inhibitor of differentiation 2,
      suggesting they are specific targets of ER signaling. These data show that NSCLC
      cells respond to estrogens/antiestrogens by altering endogenous gene expression
      and support a model in which ICI 182,780 reduces proliferation of NSCLC cells via
      its ability to disrupt ER signaling. ICI 182,780 may therefore have therapeutic
      benefit in NSCLC.

PMID- 15735051
TI  - One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer.
AB  - Accumulating evidence from epidemiologic studies suggests that risk of breast
      cancer is reduced in relation to increased consumption of folate and related B
      vitamins. We investigated independent and joint effects of B vitamin intake as
      well as two polymorphisms of a key one-carbon metabolizing gene [i.e.,
      methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer
      risk. The study uses the resources of a population-based case-control study,
      which includes 1,481 cases and 1,518 controls. Significant inverse associations
      between B vitamin intake and breast cancer risk were observed among non
      supplement users. The greatest reduction in breast cancer risk was observed among
      non-supplement users in the highest quintile of dietary folate intake [odds ratio
      (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non
      supplement users in the lowest quintile of dietary folate intake (high-risk
      individuals). The MTHFR 677T variant allele was associated with increased risk of
      breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI,
      1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely
      associated with breast cancer risk (P, trend = 0.03), and was likely due to the
      linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer
      associations were more prominent among women who did not use multivitamin
      supplements. Compared with 677CC individuals with high folate intake, elevation
      of breast cancer risk was most pronounced among 677TT women who consumed the
      lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate
      intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is
      important to identify risk factors, such as low B vitamin consumption, that may
      guide an effective prevention strategy against the disease.

PMID- 15735052
TI  - RAS, MYC, and sensitivity to tumor necrosis factor-alpha-related apoptosis
      inducing ligand-induced apoptosis.

PMID- 15735053
TI  - Ethnic disparities in the treatment of stage I non-small cell lung cancer.
AB  - RATIONALE: Important variations exist in the treatment of non-small cell lung
      cancer. Because resection is the most effective treatment for patients with early
      disease, disparities in surgical rates can generate considerable differences in
      outcomes. OBJECTIVE: We analyzed data from a national population-based registry
      to evaluate disparities in the treatment of Hispanic and white patients with
      stage I lung cancer and to assess the extent to which these inequalities explain
      survival differences. METHODS: This study included 16,036 Hispanic and white
      patients with stage I lung cancer diagnosed between 1991 and 2000. Cases were
      identified from the Surveillance, Epidemiology, and End Results registry.
      Survival was compared among white and Hispanics using Kaplan-Meier curves.
      Stratified survival curves and Cox regression were used to evaluate whether
      inequalities in stage (IA vs. IB) and resection could explain survival
      differences. RESULTS: Hispanics had worse overall and lung cancer-specific
      survival compared with whites (p = 0.04 and 0.008, respectively). Five-year lung
      cancer survival was 54% for Hispanics versus 62% for whites. Hispanics were more
      frequently diagnosed with stage IB disease (p = 0.0002) and less likely to
      undergo resection (p = 0.03). Among resected patients, survival was similar for
      the two groups, as it was among those who did not undergo unresection. After
      adjusting for surgery and stage, there was no difference in survival between
      groups. CONCLUSIONS: Hispanics with stage I lung cancer had worse survival as
      compared with whites. These disparities are largely explained by lower rates of
      resection and higher probability of diagnosis at stage IB. Future work must
      delineate why Hispanics are receiving less surgery.

PMID- 15735054
TI  - The association of acetaminophen, aspirin, and ibuprofen with respiratory disease
      and lung function.
AB  - RATIONALE: Oxidative stress may increase the risk of asthma, contribute to asthma
      progression, and decrease lung function. Previous research suggests that use of
      acetaminophen, which is hypothesized to reduce antioxidant capacity in the lung,
      is associated with an increased risk of asthma. We hypothesized that
      acetaminophen use may also be associated with chronic obstructive pulmonary
      disease (COPD) and decreased lung function. OBJECTIVES: To investigate the
      associations between use of pain medication, particularly acetaminophen, and
      asthma, COPD, and FEV1 in adults. METHODS: A cross-sectional analysis using the
      Third National Health and Nutrition Examination Survey. MEASUREMENT AND MAIN
      RESULTS: Increased use of acetaminophen had a positive, dose-dependent
      association with COPD (adjusted odds ratio for increasing category of intake,
      1.16; 95% confidence interval [CI], 1.09-1.24; p value for trend < 0.001) and an
      inverse association with lung function (daily user compared with never users, 
      54.0 ml; 95% CI, -90.3 to -17.7, adjusted). Neither of these associations was
      explained by overlap between COPD and asthma occurrence. We confirmed a dose
      response association of acetaminophen use and asthma (adjusted odds ratio, 1.20;
      95% CI, 1.12-1.28; p value for trend < 0.001). CONCLUSIONS: This study provides
      further evidence that use of acetaminophen is associated with an increased risk
      of asthma and COPD, and with decreased lung function.

PMID- 15735055
TI  - Contractile fatigue, muscle morphometry, and blood lactate in chronic obstructive
      pulmonary disease.
AB  - We hypothesized that patients with chronic obstructive pulmonary disease
      developing contractile fatigue of the quadriceps during cycle exercise may have
      characteristic metabolic and muscle features that could increase their
      susceptibility to fatigue, thus differentiating them from those who do not
      develop fatigue. We examined, in 32 patients, the fiber-type proportion,
      enzymatic activities, and capillary density in the vastus lateralis and the
      arterial blood lactate level during constant work-rate cycling exercise.
      Contractile fatigue was defined as a postexercise fall in quadriceps twitch force
      greater than 15% of resting values. Twenty-two patients developed contractile
      fatigue after exercise. No significant differences were found between fatiguers
      and non-fatiguers for the endurance time, fiber-type proportion, and oxidative
      enzyme activities. The lactate dehydrogenase activity was significantly higher (p
      < 0.05) and muscle capillarization significantly reduced in fatiguers (p < 0.05).
      Compared with non-fatiguers, the arterial lactate level during exercise was
      significantly higher in fatiguers (p < 0.001). A significant relationship was
      found between the fall in quadriceps twitch force and lactate dehydrogenase
      activity, capillary/fiber ratio, and blood lactate level. We conclude that
      changes in muscle enzymatic profile and capillarization with a greater reliance
      on glycolytic metabolism during exercise are associated with contractile fatigue
      in patients with chronic obstructive pulmonary disease.

PMID- 15735056
TI  - The bronchial lavage of pediatric patients with asthma contains infectious
      Chlamydia.
AB  - There has been a worldwide increase in the incidence of asthma, and the disease
      has greatly impacted the public health care system. Chlamydia pneumoniae has been
      reported as a possible contributing factor in asthma. The organism has been
      detected by polymerase chain reaction (PCR) in bronchial tissue, but there has
      been no direct evidence of viability. To determine the frequency of viable
      Chlamydia in children, blood and bronchoalveolar lavage were collected from 70
      pediatric patients undergoing flexible fiberoptic bronchoscopy. Forty-two of
      these patients had asthma, whereas the remaining patients had various respiratory
      disorders. Fifty-four percent (38) of the bronchoalveolar lavage samples were PCR
      positive for Chlamydia, and 31% (22) of the PCR-positive samples were positive
      when cultured on macrophages. Twenty-eight samples (40%) and 14 samples (20%) of
      the PCR- and culture-positive samples, respectively, were from patients with
      asthma. Culture of the blood samples revealed that 24 (34.3%) of 70 were positive
      for Chlamydia compared with 8 (11%) of 70 matched nonrespiratory control subjects
      (p < 0.01); 17 (24%) of the positive blood cultures from the respiratory group
      were from patients with asthma. Elevation of total IgE was strongly associated
      with lavage culture positivity for Chlamydia. We therefore conclude that viable
      Chlamydia pneumoniae organisms are frequently present in the lung lavage fluid
      from this cohort of predominantly asthmatic pediatric patients.

PMID- 15735057
TI  - Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive
      pulmonary disease.
AB  - RATIONALE: Oxidative stress is involved in the skeletal muscle dysfunction
      observed in patients with severe chronic obstructive pulmonary disease (COPD). We
      hypothesized that the diaphragms of such patients might generate greater levels
      of oxidants than those neutralized by antioxidants. OBJECTIVES: To assess the
      levels of both oxidative and nitrosative stress and different antioxidants in the
      diaphragms of those patients, and to analyze potential relationships with lung
      and respiratory muscle dysfunctions. METHODS AND MEASUREMENTS: We conducted a
      case-control study in which reactive carbonyl groups, hydroxynonenal-protein
      adducts, antioxidant enzyme levels, nitric oxide synthases, and 3-nitrotyrosine
      formation were detected using immunoblotting and immunhistochemistry in diaphragm
      specimens (thoracotomy) obtained from six patients with severe COPD, six patients
      with moderate COPD, and seven control subjects. MAIN RESULTS: Diaphragms of
      patients with severe COPD showed both higher protein carbonyl groups and
      hydroxynonenal-protein adducts than control subjects. When only considering
      patients with COPD, negative correlations were found between carbonyl groups and
      airway obstruction, and between hydroxynonenal-protein adducts and respiratory
      muscle strength. Although diaphragmatic neuronal nitric oxide synthase did not
      differ among the three groups and no inducible nitric oxide synthase was detected
      in any muscle, muscle endothelial nitric oxide synthase was lower in patients
      with severe COPD than in control subjects. Muscle nitrotyrosine levels were
      similar in both patients with severe COPD and control subjects. CONCLUSIONS: This
      study shows that oxidative stress rather than nitric oxide is likely to be
      involved in the respiratory muscle dysfunction in severe COPD.

PMID- 15735059
TI  - Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary
      alveolar proteinosis.
AB  - The anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody
      is inferred to cause idiopathic pulmonary alveolar proteinosis (iPAP): the
      antibody neutralizes GM-CSF and thereby impairs differentiation of alveolar
      macrophages. Administration of GM-CSF improves respiratory function of patients
      with iPAP, as confirmed in this study using aerosolized GM-CSF. To elucidate its
      mechanism, we characterized bronchoalveolar lavage fluid and alveolar macrophages
      obtained from three patients with iPAP who were treated successfully with
      aerosolized GM-CSF. Cell number, expressions of surface mannose receptor and the
      transcription factor PU.1, and phagocytic ability of alveolar macrophages were
      all restored to control levels. With treatment, the neutralizing capacity of GM
      CSF activity was reduced markedly, concomitant with the decreasing autoantibody
      levels. Interestingly, the amount of GM-CSF autoantibody complex also decreased.
      In one case in which the complex was analyzed, the majority of GM-CSF binding the
      complex was endogenous protein, suggesting that the complex is removed
      immediately from the lung after treatment. Our study shows that GM-CSF
      administration engenders a decrease in the neutralizing capacity against the
      protein in the lungs. Thereby, it facilitates restoration of the normal function
      of alveolar macrophages.

PMID- 15735058
TI  - Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a
      human inhalation study.
AB  - RATIONALE: Zinc oxide is a common, biologically active constituent of particulate
      air pollution as well as a workplace toxin. Ultrafine particles (< 0.1 microm
      diameter) are believed to be more potent than an equal mass of inhaled
      accumulation mode particles (0.1-1.0 microm diameter). OBJECTIVES: We compared
      exposure-response relationships for respiratory, hematologic, and cardiovascular
      endpoints between ultrafine and accumulation mode zinc oxide particles. METHODS:
      In a human inhalation study, 12 healthy adults inhaled 500 microg/m3 of ultrafine
      zinc oxide, the same mass of fine zinc oxide, and filtered air while at rest for
      2 hours. MEASUREMENTS AND MAIN RESULTS: Preexposure and follow-up studies of
      symptoms, leukocyte surface markers, hemostasis, and cardiac electrophysiology
      were conducted to 24 hours post-exposure. Induced sputum was sampled 24 hours
      after exposure. No differences were detected between any of the three exposure
      conditions at this level of exposure. CONCLUSIONS: Freshly generated zinc oxide
      in the fine or ultrafine fractions inhaled by healthy subjects at rest at a
      concentration of 500 microg/m3 for 2 hours is below the threshold for acute
      systemic effects as detected by these endpoints.

PMID- 15735060
TI  - Inhibition of c-Jun N-terminal kinase limits lipopolysaccharide-induced pulmonary
      neutrophil influx.
AB  - The influx of neutrophils into the lung is a sentinel event in LPS-induced acute
      lung inflammation. Previous studies have shown that systemic inhibition of p38
      decreases LPS-induced neutrophil influx into the alveolar space but has no effect
      on pulmonary parenchymal neutrophil accumulation or on microvascular leak,
      indicating other pathways are important in LPS-induced acute lung inflammation.
      This study examined the role of c-Jun N-terminal kinase in LPS-induced acute lung
      inflammation. Systemic inhibition of c-Jun N-terminal kinase, with the specific c
      Jun N-terminal kinase inhibitor SP600125, decreased the LPS-induced accumulation
      of neutrophils into the lung parenchyma and alveolar space. In addition,
      increases in microvascular leak after LPS exposure were diminished by c-Jun N
      terminal kinase inhibition. To determine mechanisms by which systemic c-Jun N
      terminal kinase inhibition decreased pulmonary neutrophil influx, LPS and tumor
      necrosis factor alpha (TNF-alpha-)-induced neutrophil actin assembly and
      retention were examined. Neutrophil actin assembly was decreased after LPS and
      TNF-alpha stimulation with SP600125 pretreatment, as well as LPS-induced
      neutrophil retention. Finally, c-Jun N-terminal kinase inhibition decreased Cdc42
      activation after LPS or TNF-alpha stimulation, thereby providing one mechanism by
      which c-Jun N-terminal kinase inhibition decreased actin assembly, and thereby
      pulmonary neutrophil accumulation.

PMID- 15735061
TI  - Habituation of arousal responses after intermittent hypercapnic hypoxia in
      piglets.
AB  - RATIONALE: Clinical studies have demonstrated arousal deficits in infants
      suffering obstructive sleep apnea, and some infant deaths have been attributed to
      such an arousal deficit. OBJECTIVES: To evaluate whether arousal deficits can be
      induced by intermittent asphyxia during normal development. METHODS AND
      MEASUREMENTS: Young piglets were exposed to intermittent hypercapnic hypoxia for
      4 days from age 9.55 +/- 0.5 days. Arousal responses were compared between
      control animals and animals exposed to intermittent hypercapnic hypoxia. Outcome
      measures included time to arouse after onset of the respiratory stimulus and
      frequency of arousals during recovery. MAIN RESULTS: Arousal deficits emerged
      after successive exposures to hypercapnic hypoxia on Day 1, and were exacerbated
      on Day 4, although after overnight recovery, the deficit only became evident
      during the second and subsequent episode of hypercapnic hypoxia. On Day 1, time
      to arouse increased from 16.9 +/- 7.1 seconds in the first epoch to 41.7 +/- 28.6
      seconds in the fourth epoch (p = 0.004 between cycles, one-way analysis of
      variance). In the recovery periods after hypercapnic hypoxia, there were 64%
      fewer arousals than baseline on Day 1 and 90% fewer arousals on Day 4.
      Respiratory effort, measured by VT across 10 breaths before the arousal,
      increased from 25.7 +/- 7.6 on Day 1 to 29.1 +/- 6.8 ml/kg on Day 4 (p < 0.001,
      two-way analysis of variance, Day 4 vs. Day 1, respectively). CONCLUSIONS: These
      studies demonstrate that acute and chronic arousal deficits can be induced by
      intermittent asphyxia, on a background of otherwise normal postnatal development.

PMID- 15735062
TI  - Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in
      mice.
AB  - Imatinib mesylate is a potent and specific tyrosine kinase inhibitor against c
      ABL, BCR-ABL, and c-KIT, and has been demonstrated to be highly active in chronic
      myeloid leukemia and gastrointestinal stromal tumors. We examined the
      antifibrotic effects of imatinib using a bleomycin-induced lung fibrosis model in
      mice because imatinib also inhibits tyrosine kinase of platelet-derived growth
      factor receptors (PDGFRs). Imatinib inhibited the growth of primary murine lung
      fibroblasts and the autophosphorylation of PDGFR-beta induced by PDGF.
      Administration of imatinib significantly prevented bleomycin-induced pulmonary
      fibrosis in mice, partly by reducing the number of mesenchymal cells
      incorporating bromodeoxyuridine. Analysis of bronchoalveolar lavage cells
      demonstrated that imatinib did not suppress early inflammation on Days 7 and 14
      caused by bleomycin. These results suggest that imatinib has the potential to
      prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells,
      and that imatinib might be useful for the treatment of pulmonary fibrosis in
      humans.

PMID- 15735063
TI  - Roles for cell death in zinc deficiency.
AB  - Studies of zinc deficiency (ZD) have become important for demonstrating that
      nutritional imbalances can readily induce programmed cell death (PCD) or
      apoptosis in a variety of kinds of cells. In mice, ZD caused a 300% increase in
      the amount of apoptosis among pre T-cells, which was a major cause of thymic
      atrophy that alters host defense. Embryogenesis was significantly altered in ZD
      mice due to increased apoptosis in the neural crest, optic, and head regions.
      Insufficient zinc initiated PCD in hepatocytes, glioma, kidney, monocytes,
      fibroblasts, and testicular cells, demonstrating the scope of this phenomenon.
      New forms of cell death continue to emerge. For example, autophagy is initiated
      by starvation and various nutritional and metabolic imbalances. Autophagy is a
      form of PCD whereby the cell digests some of its own organelles to provide needed
      nutrients. Understanding the interplay between these different forms of cell
      death and nutritional imbalances is very important because of their profound
      impact on development, growth, immune function, and health.

PMID- 15735064
TI  - The discovery of the antioxidant function of vitamin E: the contribution of Henry
      A. Mattill.

PMID- 15735065
TI  - Meal feeding alters translational control of gene expression in rat liver.
AB  - Meal feeding after a period of food deprivation results in a subsequent increase
      in the protein and RNA content of the liver. To gain insight into the mechanisms
      involved in the response to food intake, changes in the association of selected
      mRNAs with polysomes were examined. On the day of the study, rat livers were
      collected at 0, 15, 60, and 180 min after the start of feeding and analyzed for
      biomarkers of the translational control of protein synthesis. Protein synthesis
      was increased within 60 min and was sustained for 180 min. Assembly of the active
      eukaryotic initiation factor (eIF) 4F complex was elevated within 15 min, as
      indicated by the relative association of eIF4E . eIF4G, but returned to the basal
      value within 180 min. Phosphorylation of the ribosomal protein (rp) S6 kinase
      S6K1 and its substrate rpS6 was increased within 15 min and was sustained for at
      least 180 min. Both eIF4F assembly and activation of S6K1 have been linked to
      upregulated translation of a subset of mRNAs. To identify translationally
      regulated mRNAs, polysomal (i.e., actively translated) and nonpolysomal
      (nontranslated) fractions were isolated and subjected to microarray analysis. The
      mRNAs encoding 78 proteins, including 42 proteins involved in protein synthesis,
      exhibited increased abundance in polysomes in response to feeding. Overall, the
      results demonstrate that protein synthesis as well as ribosomal protein mRNA
      translation undergo rapid and sustained stimulation in the liver after meal
      feeding and thus contribute to the previously observed increases in protein and
      RNA content.

PMID- 15735066
TI  - Oral leucine administration stimulates protein synthesis in rat skeletal muscle.
AB  - Oral administration of a single bolus of leucine in an amount equivalent to the
      daily intake (1.35 g/kg body wt) enhances skeletal muscle protein synthesis in
      food-deprived rats. To elucidate whether smaller amounts of leucine can also
      stimulate protein synthesis, rats were administered the amino acid at
      concentrations ranging from 0.068 to 1.35 g/kg body wt by oral gavage. Thirty
      minutes following the administration of doses of leucine as low as 0.135 g/kg
      body wt, skeletal muscle protein synthesis was significantly greater than control
      values. The increase in protein synthesis was associated with changes in the
      regulation of biomarkers of mRNA translation initiation as evidenced by
      upregulated phosphorylation of the translational repressor, eukaryotic initiation
      factor (eIF)4E-binding protein 1 (4E-BP1), the association of eIF4G with the mRNA
      cap binding protein eIF4E, and the phosphorylation of the 70-kDa ribosomal
      protein S6 kinase. Alterations in the phosphorylation of eIF4G, as well as the
      association of 4E-BP1 with eIF4E, were observed following leucine administration;
      however, these changes appeared to be biphasic with maximal changes occurring
      when circulating insulin concentrations were elevated. Thus it appears that
      leucine administration affects mRNA translation and skeletal muscle protein
      synthesis through modulation of multiple biomarkers of mRNA translation. The
      ability of small doses of leucine to stimulate skeletal muscle protein synthesis
      suggests that future research on the regulation of skeletal muscle protein
      synthesis by orally administered leucine will be feasible in humans.

PMID- 15735067
TI  - Plasma homocysteine concentrations in Greek children are influenced by an
      interaction between the methylenetetrahydrofolate reductase C677T genotype and
      folate status.
AB  - Risk factors established at young ages may set the stage for later cardiovascular
      disease (CVD). Elevated total homocysteine (tHcy) in blood is an emerging risk
      factor for CVD, yet few studies have been conducted in children, especially in
      the Mediterranean. We described plasma tHcy concentrations in a group of healthy
      Greek children and examined its relation with physiologic, metabolic, and genetic
      variables. Fasting blood samples were collected from 186 students, 11.6 +/- 0.4
      years old, and tHcy, folate, vitamin B-12, and routine biochemistry variables in
      plasma were measured. The methylenetetrahydrolate reductase (MTHFR) C677T
      genotype was determined and anthropometric and dietary data were obtained. The
      distribution of tHcy was positively skewed with a median of 7.9 micromol/L (mean:
      8.2 +/- 2.3 micromol/L; range: 4.4-22.2 micromol/L). tHcy was inversely related
      to plasma folate (r = -0.34, P < 0.0001), vitamin B-12 (r = -0.20, P = 0.008),
      and glucose (r = -0.15, P = 0.045). An interaction between the MTHFR genotype and
      plasma folate on tHcy was detected (P = 0.047). Specifically, the homozygous
      mutant TT genotype was associated with higher tHcy only in children with lower
      plasma folate (< 19.9 nmol/L), (P = 0.012). In our sample of healthy Greek
      children, plasma tHcy concentrations were higher than values reported in children
      of Northern European descent and were associated with folate, vitamin B-12, and
      glucose in plasma. The results also show that, similar to adults, plasma folate
      concentration is important in determining the contribution of the MTHFR C677T
      mutation to tHcy concentrations in children.

PMID- 15735068
TI  - Methylenetetrahydrofolate reductase 677C->T polymorphism and folate status affect
      one-carbon incorporation into human DNA deoxynucleosides.
AB  - The methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism is thought
      to influence the partitioning of 1-carbon units between methylation and other
      components of 1-carbon metabolism and to influence the risk and etiology of
      several major cancers and cardiovascular disease. Our objective was to determine
      the effect of the MTHFR 677C-->T polymorphism and folate status on the relative
      rate and extent of in vivo synthesis of DNA precursors. Adequately nourished,
      healthy women (9 CC, 9 TT) were infused with [3-(13)C]serine and
      [(13)C(5)]methionine for 9 h before and after 7 wk of consumption of a low-folate
      diet. Blood was drawn over 5 d for monocyte DNA isolation. Isotopic enrichment of
      the nucleosides in DNA digests was determined by LC-MS/MS. Maximum thymidine
      enrichment tended to be higher (P = 0.07) in TT than in CC subjects, suggestive
      of marginally higher mean thymidylate synthesis. However, the subset of TT
      subjects who exhibited formyltetrahydrofolate in erythrocytes (an indicator of 1
      carbon partitioning) had greater (P = 0.036) thymidine enrichment than CC
      subjects, who had no erythrocyte formyltetrahydrofolate. Purine enrichment was
      not affected by genotype or folate depletion. However, the deoxyadenosine to
      deoxyguanosine enrichment ratio was significantly higher in TT subjects,
      suggesting a greater relative rate of adenine synthesis. The approximately 40%
      greater (P = 0.012) labeling of the methyl group of methyldeoxycytidine during
      folate depletion suggests a change in the origin of this 1-carbon unit. This is
      the first time that 1-carbon incorporation into human DNA has been measured in
      vivo after infusion of (13)C-labeled 1-carbon precursors. These findings support
      the feasibility of further assessment of factors affecting deoxynucleotide
      synthesis and DNA methylation in human 1-carbon metabolism.

PMID- 15735069
TI  - Polyunsaturated fatty acids interact with the PPARA-L162V polymorphism to affect
      plasma triglyceride and apolipoprotein C-III concentrations in the Framingham
      Heart Study.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear
      transcription factor regulating multiple genes involved in lipid metabolism. It
      was shown that a common leucine to valine (L162V) substitution at the PPARalpha
      gene (PPARA) is functional and affects transactivation activity of PPARalpha
      ligands, such as PUFA, on a concentration-dependent basis. The current study
      examined this gene-nutrient interaction in relation to plasma lipid variables in
      a population-based study consisting of 1003 men and 1103 women participating in
      the Framingham cohort and consuming their habitual diets. We found significant
      gene-nutrient interactions between the L162V polymorphism and total PUFA intake,
      which modulated plasma triglycerides (TG; P < 0.05) and apolipoprotein C-III
      (apoC-III; P < 0.05) concentrations. The 162V allele was associated with greater
      TG and apoC-III concentrations only in subjects consuming a low-PUFA diet (below
      the population mean, 6% of energy). However, when PUFA intake was high, carriers
      of the 162V allele had lower apoC-III concentrations. This interaction was
      significant even when PUFA intake was considered as a continuous variable (P =
      0.031 for TG and P < 0.001 for apoC-III), suggesting a strong dose-response
      effect. When PUFA intake was <4%, 162V allele carriers had approximately 28%
      higher plasma TG than did 162L homozygotes (P < 0.01). Conversely, when PUFA
      intake was >8%, plasma TG in 162V allele carriers was 4% lower than in 162L
      homozygotes. Similar results were obtained for (n-6) and (n-3) fatty acids. Our
      data show that the effect of the L162V polymorphism on plasma TG and apoC-III
      concentrations depends on the dietary PUFA, with a high intake triggering lower
      TG in carriers of the 162V allele.

PMID- 15735070
TI  - An acute ileal amino acid digestibility assay is a valid procedure for use in
      human ileostomates.
AB  - An acute (24-h) feeding/digesta sampling procedure was evaluated in a preliminary
      study using growing pigs. The validated acute procedure was then applied using
      human ileostomates to determine apparent and true ileal amino acid
      digestibilities of 4 dietary protein sources. The acute method involved feeding
      ileostomized pigs a single meal containing the test protein as part of a purified
      diet, with no previous dietary adaptation, followed by an 8-h collection of
      digesta. Apparent ileal N digestibility did not differ between the acute and
      conventional (14-d study) procedures. Eight adult human ileostomates each
      received a single meal of protein-free biscuits and a drink containing sodium
      caseinate, whey protein concentrate, soy protein isolate, or soy protein
      concentrate; this meal was followed by a 9-h total digesta collection period.
      Acid insoluble ash was used as an indigestible marker. True ileal amino acid
      digestibilities (means +/- SE) ranged from 90.5 +/- 2.74% for cysteine in soy
      protein concentrate to 105.3 +/- 5.66% for cysteine in sodium caseinate and were
      markedly higher than their apparent counterparts. True ileal digestibilities for
      total nitrogen were 101.9 +/- 0.70, 98.3 +/- 0.80, 99.5 +/- 0.80, and 98.5 +/-
      1.20% for sodium caseinate, whey protein concentrate, soy protein isolate, and
      soy protein concentrate, respectively. The 4 protein sources were virtually
      completely digested in humans by the end of the small intestine.

PMID- 15735071
TI  - A nutritional intervention promoting the Mediterranean food pattern is associated
      with a decrease in circulating oxidized LDL particles in healthy women from the
      Quebec City metropolitan area.
AB  - The aim of the present study was to evaluate the effect of a nutritional
      intervention promoting the Mediterranean food pattern under free-living
      conditions on circulating oxidized LDL (ox-LDL) in a group of 71 healthy women
      from the Quebec City metropolitan area. The 12-wk nutritional intervention
      consisted of 2 courses on nutrition and 7 individual sessions with a dietitian. A
      score based on the 11 components of the Mediterranean pyramid was established to
      determine the women's adherence to the Mediterranean food pattern. Plasma ox-LDL
      concentrations were measured by a monoclonal antibody mAb-4E6-based competition
      ELISA. Among all women, plasma ox-LDL decreased by 11.3% after 12 wk of
      nutritional intervention (P < 0.0001) despite a lack of change in plasma LDL
      cholesterol (LDL-C). Also, an increase in the Mediterranean dietary score was
      significantly correlated with a decrease in ox-LDL concentrations (r = -0.30; P =
      0.01). More specifically, increases in servings of fruits (r = -0.25; P < 0.05)
      and vegetables (r = -0.24; P < 0.05) were associated with decreases in ox-LDL
      concentrations. Changes in the food pattern in response to a nutritional
      intervention promoting the Mediterranean food pattern were accompanied by
      beneficial effects in circulating ox-LDL concentrations in healthy women.

PMID- 15735072
TI  - Dietary fat type influences total milk fat content in lean women.
AB  - Trans fatty acids (TFA) are found naturally in some foods (e.g., dairy products)
      as well as many processed foods made with partially hydrogenated vegetable oils
      (PHVO). Data from a growing literature suggest that some TFA decrease milk fat in
      lactating animals. Because the physiologic effects of TFA in lactating women are
      unknown, this study was designed to investigate the effects of TFA consumption on
      human milk fat. A randomized, crossover design (n = 12) was used to study the
      effect of 3 dietary treatments: high PHVO (regular margarine), low PHVO (low TFA
      margarine), or low PHVO but high in naturally occurring TFA (butter) on milk fat.
      Treatments were administered for 5 d, with 7-d washout periods. Maternal
      adiposity was estimated by dual-energy X-ray absorptiometry. Milk and blood were
      collected on d 5 of each intervention period. In general, milk and serum fatty
      acid concentrations mirrored those of the dietary treatments. There were
      significant interactions between treatment and maternal adiposity on milk fat and
      infant milk consumption, as well as on serum glucose and nonesterified fatty acid
      (NEFA) concentrations. Consumption of regular margarine, compared with low TFA
      margarine, resulted in lower milk fat in leaner, but not in more obese women.
      Consumption of either regular or low TFA margarine, compared with butter,
      elevated serum NEFA concentrations in the more obese women. In summary,
      consumption of regular margarine, compared with low TFA margarine, decreased milk
      fat in lean women. Further studies are required to determine whether infant milk
      consumption might compensate for this potentially important change in milk
      composition.

PMID- 15735073
TI  - Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not
      alter milk fat or immunity in lactating women.
AB  - Isomers of conjugated linoleic acid (CLA) decreased milk fat, altered immunity,
      and reduced the risk for cardiovascular disease (CVD) in some animals. The major
      form of CLA in the human diet is c9,t11-18:2 (rumenic acid; RA). We studied the
      effects of high RA consumption on plasma and milk RA concentration, milk
      composition, immunity, and CVD risk factors in lactating women (n = 36) assigned
      to 1 of 3 treatments: control, low CLA cheese (LCLA; 160 mg RA/d), or high CLA
      cheese (HCLA; 346 mg RA/d). The increase in plasma RA concentration between
      baseline and 8 wk in women consuming HCLA cheese was significantly greater than
      that of controls. At study completion (8 wk), milk RA concentration among women
      consuming HCLA cheese was greater (P < 0.05) than that of controls (0.37 vs.
      0.26% of fatty acids). Treatment did not affect milk fat, protein, or lactose
      concentrations, immune indices (e.g., plasma T-helper cells and interleukin-2),
      or measured risk factors for CVD (e.g., plasma triacylglyceride and cholesterol).
      In summary, consumption of a RA-enriched cheese modestly increased plasma and
      milk RA concentrations without affecting total milk fat, plasma and milk indices
      of immunity, or selected risk factors for CVD.

PMID- 15735074
TI  - Carotenoid absorption from salad and salsa by humans is enhanced by the addition
      of avocado or avocado oil.
AB  - Dietary lipids are hypothesized to be an important factor for carotenoid
      bioavailability. However, most carotenoid-rich fruits and vegetables are low in
      lipids. The objective of this study was to assess whether the addition of avocado
      fruit as a lipid source enhances carotenoid absorption in humans. Healthy
      subjects (n = 11/study) were recruited for 2 crossover, postprandial studies. The
      effect of avocado addition (150 g) to salsa on lycopene and beta-carotene
      absorption was examined in Study 1, and the absorption of lutein, alpha-carotene,
      and beta-carotene from salad in Study 2. Furthermore, the effects of avocado dose
      (75 vs. 150 g containing 12 vs. 24 g lipid, respectively) and of lipid source
      (avocado fruit vs. avocado oil) on carotenoid absorption were examined in Study
      2. Intact carotenoids were quantified in the plasma triacylglycerol-rich
      lipoprotein (TRL) fraction during the 9.5 h after consumption of the test meal
      and expressed as baseline-corrected area under the concentration-vs.-time curve
      (AUC). The addition of avocado to salsa enhanced lycopene and beta-carotene
      absorption (P < 0.003), resulting in 4.4 and 2.6 times the mean AUC after intake
      of avocado-free salsa, respectively. In Study 2, supplementing 150 g avocado or
      24 g avocado oil to salad similarly enhanced alpha-carotene, beta-carotene, and
      lutein absorption (P < 0.01), resulting in 7.2, 15.3, and 5.1 times the mean AUC
      after intake of avocado-free salad, respectively (150 g avocado). Neither the
      avocado dose nor the lipid source affected carotenoid absorption. In conclusion,
      adding avocado fruit can significantly enhance carotenoid absorption from salad
      and salsa, which is attributed primarily to the lipids present in avocado.

PMID- 15735075
TI  - The nutritional status of astronauts is altered after long-term space flight
      aboard the International Space Station.
AB  - Defining optimal nutrient requirements is critical for ensuring crew health
      during long-duration space exploration missions. Data pertaining to such nutrient
      requirements are extremely limited. The primary goal of this study was to better
      understand nutritional changes that occur during long-duration space flight. We
      examined body composition, bone metabolism, hematology, general blood chemistry,
      and blood levels of selected vitamins and minerals in 11 astronauts before and
      after long-duration (128-195 d) space flight aboard the International Space
      Station. Dietary intake and limited biochemical measures were assessed during
      flight. Crew members consumed a mean of 80% of their recommended energy intake,
      and on landing day their body weight was less (P = 0.051) than before flight.
      Hematocrit, serum iron, ferritin saturation, and transferrin were decreased and
      serum ferritin was increased after flight (P < 0.05). The finding that other
      acute-phase proteins were unchanged after flight suggests that the changes in
      iron metabolism are not likely to be solely a result of an inflammatory response.
      Urinary 8-hydroxy-2'-deoxyguanosine concentration was greater and RBC superoxide
      dismutase was less after flight (P < 0.05), indicating increased oxidative
      damage. Despite vitamin D supplement use during flight, serum 25
      hydroxycholecalciferol was decreased after flight (P < 0.01). Bone resorption was
      increased after flight, as indicated by several markers. Bone formation, assessed
      by several markers, did not consistently rise 1 d after landing. These data
      provide evidence that bone loss, compromised vitamin D status, and oxidative
      damage are among critical nutritional concerns for long-duration space travelers.

PMID- 15735076
TI  - Low nutrient intakes among infants in rural Bangladesh are attributable to low
      intake and micronutrient density of complementary foods.
AB  - We assessed the adequacy of nutrient intakes of 135 rural Bangladeshi breast-fed
      infants 6-12 mo of age and examined nutritional trade-offs due to possible
      displacement of breast milk by complementary foods. Observers completed 12-h
      daytime measurements of breast milk and complementary food intakes; data for the
      previous 12 h were obtained from maternal recall, yielding estimates of total 24
      h intakes. On average, infants were mildly wasted (mean +/- SD weight-for-length
      Z-score = -0.92 +/- 0.88) and moderately stunted (length-for-age Z-score = -1.49
      +/- 0.96). Total energy intakes at 6-8 and 9-12 mo were 88 and 86% of absolute
      energy requirements (kJ/d), 106 and 105% of requirements per kg body weight, and
      97 and 94% of requirements per kg median weight-for-length, respectively. Breast
      milk contributed 78% of energy intake at 6-8 mo and 75% at 9-12 mo. Mean meal
      frequency and energy density of complementary foods were generally consistent
      with recommendations, but only small amounts of food were offered. Nevertheless,
      only 72% of the food energy offered was consumed. Total energy intake was
      positively correlated with meal frequency, quantity consumed per meal, and energy
      intake from breast milk, but not with energy density of complementary foods.
      Energy intake from complementary foods was inversely related to energy intake
      from breast milk. The diets fell short of recommended intakes for numerous
      vitamins and minerals. We conclude that although greater intakes of complementary
      foods were associated with higher total energy intake, micronutrient intake
      remained low due to the low micronutrient density of the complementary foods
      consumed and the partial displacement of breast milk.

PMID- 15735077
TI  - The prevalence of wasting, but not stunting, has improved in the Democratic
      People's Republic of Korea.
AB  - The Democratic People's Republic of Korea (DPRK) is one of the nutritionally
      vulnerable countries of the world. The objectives of this paper were to determine
      the current prevalence of undernutrition among children using data from the
      latest national survey and to compare the findings with those from the previous
      national survey in 1997. In 2002 with cooperation from UNICEF and the World Food
      Program (WFP), the government of the DPRK conducted a survey of 6000 households
      with children < 7 y old using multiple-stage sampling methods. Data were
      collected for sociodemographic variables, use of WFP food aid, and anthropometric
      measures of the youngest child in the household. The prevalence of stunting
      (height for age Z-score less than -2.0) in all children was 39.4% (40.2 and 38.5%
      for boys and girls, respectively). The prevalence of wasting (weight for height Z
      score less than -2.0) was 8.2% in all children (9.1 and 7.3% for boys and girls,
      respectively). Although the prevalence of wasting has decreased from 1997 (16.5%)
      to 2002 (8.2%), the prevalence of stunting has not changed between those years,
      38.2 vs. 39.4%. Thus, we conclude that acute undernutrition is decreasing in the
      DPRK, but chronic undernutrition that results in stunting is still highly
      prevalent. Continued surveillance of nutritional status of children in the DPRK
      is warranted given the continued state of undernutrition in that country.

PMID- 15735078
TI  - A young child feeding index is not associated with either height-for-age or
      height velocity in rural Senegalese children.
AB  - Ruel and Menon recently published a young child feeding index based on
      characteristics taken from 24-h and 7-d recalls. A strong positive association
      was found in 7 Latin American Demographic and Health Surveys for 12- to 36-mo-old
      children (1). The aim of this study was to test for associations of this index
      with height-for-age and linear growth in African children. Children (n = 500),
      aged 12-42 mo, living in a rural area of Senegal were visited in their homes in
      April-May, and 24-h and 7-d food recalls were conducted with their mothers.
      Height was measured, and measurements taken 7 mo earlier were used to compute
      linear growth rates. General linear models were used to adjust for potential
      confounders (child age and sex, maternal height, BMI, and socioeconomic status).
      The feeding index was not associated with either height-for-age (adjusted means: 
      1.01, -1.06, and -1.20 Z-scores for the 1st, 2nd, and 3rd tercile, respectively)
      or with linear growth (6.2, 6.0, and 6.3 cm/7 mo for the 3 terciles,
      respectively). Continuing breast-feeding was negatively associated with height
      for-age (P < 0.05) and positively associated with linear growth (P < 0.01).
      Frequent consumption of fruit was positively associated with both (P = 0.059 and
      P = 0.027, respectively, in adjusted models), whereas food consumption from an
      animal source was not. In conclusion, the composite feeding index was independent
      of height and linear growth in these rural African children, due in part to
      reverse causality between breast-feeding duration and stunting.

PMID- 15735079
TI  - The addition of milk or yogurt to a plant-based diet increases zinc
      bioavailability but does not affect iron bioavailability in women.
AB  - The addition of milk and milk-based products to the diets of individuals
      subsisting on plant-based diets was reported to have positive effects on
      nutritional status and functional outcomes such as growth, morbidity, and
      cognition. We examined the effect of the addition of milk or yogurt on the
      bioavailability of zinc and iron from a plant-based rural diet. The subjects were
      48 Mexican women (30.9 +/- 5.7 y) who habitually consumed a plant-based diet. The
      women were assigned to 1 of 3 groups: 1) the typical rural Mexican diet, 2) that
      diet with milk added, or 3) that diet with yogurt for 13 d. Zinc absorption was
      measured after extrinsically labeling meals with (67)Zn and an i.v. dose of
      (70)Zn; iron absorption was measured by extrinsically labeling meals with (58)Fe
      and a reference oral dose of (57)Fe. Including milk and yogurt in the diet
      increased zinc absorption by 50 and 68%, respectively (P < 0.05). The 3 groups
      did not differ in the percentage iron absorption. The total amount of zinc
      absorbed was increased (P < 0.05) by 70% when milk was added to the meal and 78%
      when yogurt was added. The total amount of iron absorbed did not differ among the
      groups. The addition of milk and yogurt to a plant-based diet high in phytate
      increases zinc bioavailability without affecting iron bioavailability.

PMID- 15735080
TI  - Muscle fractional protein synthesis is higher in Iberian than in Landrace growing
      pigs fed adequate or lysine-deficient diets.
AB  - Protein deposition in Iberian pigs is low and the reasons for this are unknown.
      We investigated differences in protein synthesis rate in tissues of 30 Iberian
      and Landrace gilts fed 2 diets with adequate amino acid composition containing
      160 or 120 g crude protein (CP)/kg, or a lysine-deficient diet (containing 120 or
      160 g CP/kg for Iberian and Landrace pigs, respectively). Pigs were infused with
      a flooding dose of phenylalanine (15% as [(2)H(5)]-phenylalanine). Blood samples
      were taken from 12 to 40 min after the start of infusion, and samples from
      longissimus dorsi (ld), biceps femoris (bf), and semimembranosus (sm) muscles,
      liver, and duodenum were taken after slaughter. Body weights (BW) were 22.9 +/-
      0.37 and 27.1 +/- 0.64 kg for Iberian and Landrace pigs, respectively. Iberian
      pigs fed the adequate diets had higher muscle fractional protein synthesis rates
      (FSR, %/d) than Landrace pigs. The FSR were 7.9 +/- 0.34 vs. 6.3 +/- 0.29%/d; 8.3
      +/- 0.36 vs. 6.3 +/- 0.21%/d, and 7.7 +/- 0.23 vs. 6.4 +/- 0.36%/d for ld, bf,
      and sm muscles in Iberian and Landrace breeds, respectively (P < 0.01). However,
      muscles were between 20 and 32% smaller in the Iberian pigs (P < 0.01). Dietary
      protein level did not affect muscle FSR or size in either breed. Lysine
      deficiency reduced muscle FSR (46-49%, P < 0.001). Visceral tissues had greater
      relative weights in Iberian pigs (P < 0.001) with no breed differences in FSR.
      These findings might explain the low efficiency of protein and energy utilization
      by Iberian pigs compared with conventional pig breeds.

PMID- 15735081
TI  - Hypoenergetic high-carbohydrate or high-fat parenteral nutrition induces a
      similar metabolic response with differential effects on hepatic IGF-I mRNA in
      dexamethasone-treated rats.
AB  - The optimal level of energy for critically ill patients who require parenteral
      nutrition (PN) is unclear. Our objective was to determine whether 50% energy
      (50%E) restriction due to a reduction in carbohydrate or fat, with provision of
      adequate protein and micronutrients, ameliorates the detrimental effects of
      dexamethasone (Dex) on body protein catabolism, insulin resistance, and insulin
      like growth factor-I (IGF-I) responses in rats administered PN. The experiment
      included 6 PN groups, adequate energy (AE) +/- Dex, 50% AE with high carbohydrate
      (50%E CHO) +/- Dex and 50% AE with high fat (50%E FAT) +/- Dex. There was a
      significant interaction between energy level and Dex such that the increase in
      body catabolism due to 50%E from CHO or FAT was reduced by approximately 50%,
      although the amount of body weight and nitrogen lost over 7 d was significantly
      greater with 50%E than with AE. AE+Dex induced a 60% increase in liver mass,
      whereas 50%E+Dex reduced the increase to 26%. AE+Dex induced a 5-fold increase in
      serum insulin level, whereas 50%E+Dex normalized the insulin to glucose ratio.
      Serum IGF-I levels were reduced 14-18% by Dex and 30% by 50%E. Hepatic
      immunoreactive IGF-I was significantly correlated with serum IGF-I and nitrogen
      balance. 50%E CHO and 50%E FAT had differential effects on hepatic IGF-I mRNA
      with a 40% decrease in IGF-I mRNA due to 50%E FAT+Dex. In summary,CHO or FAT
      hypoenergetic PN with adequate protein had similar effects in normalizing
      hyperinsulinemia, attenuating hepatomegaly, and reducing the increment, but not
      the total amount of body protein catabolism, induced by glucocorticoid excess.

PMID- 15735082
TI  - Dietary threonine restriction specifically reduces intestinal mucin synthesis in
      rats.
AB  - We determined whether the steady-state levels of intestinal mucins are more
      sensitive than total proteins to dietary threonine intake. For 14 d, male Sprague
      Dawley rats (158 +/- 1 g, n = 32) were fed isonitrogenous diets (12.5% protein)
      containing 30% (group 30), 60% (group 60), 100% (control group), or 150% (group
      150) of the theoretical threonine requirement for growth. All groups were pair
      fed to the mean intake of group 30. The mucin and mucosal protein fractional
      synthesis rates (FSR) did not differ from controls in group 60. By contrast, the
      mucin FSR was significantly lower in the duodenum, ileum, and colon of group 30
      compared with group 100, whereas the corresponding mucosal protein FSR did not
      differ. Because mucin mRNA levels did not differ between these 2 groups, mucin
      production in group 30 likely was impaired at the translational level. Our
      results clearly indicate that restriction of dietary threonine significantly and
      specifically impairs intestinal mucin synthesis. In clinical situations
      associated with increased threonine utilization, threonine availability may limit
      intestinal mucin synthesis and consequently reduce gut barrier function.

PMID- 15735083
TI  - Dietary fatty acids and cholesterol differentially modulate HDL cholesterol
      metabolism in Golden-Syrian hamsters.
AB  - Dietary fatty acids alter HDL cholesterol concentrations, presumably through
      mechanisms related to reverse cholesterol transport. The effect of dietary fats
      (coconut oil, butter, traditional stick margarine, soybean oil, canola oil)
      differing in fatty acid profile on this antiatherogenic process was assessed with
      respect to plasma lipids; exogenous and endogenous lecithin-cholesterol
      acyltransferase (LCAT), cholesterol ester transfer protein (CETP), phospholipid
      transfer protein (PLTP) activities; and LCAT, apolipoprotein (apo) A-I and
      scavenger receptor B class-1 (SR-B1) mRNA abundance. Golden-Syrian hamsters were
      fed a nonpurified (6.25 g/100 g fat) diet containing an additional 10 g/100 g
      experimental fat and 0.1 g/100 g cholesterol for 6 wk. Canola and soybean oils
      significantly lowered serum HDL cholesterol concentrations relative to butter.
      Canola oil, relative to butter, resulted in higher exogenous LCAT activity, and
      both soybean and canola oils significantly increased hepatic apo A-I and SR-B1
      mRNA abundance. Butter, relative to margarine, coconut and soybean oils,
      significantly increased serum non-HDL cholesterol concentrations. Endogenous and
      exogenous LCAT, CETP, and PLTP activities did not differ in hamsters fed
      margarine or saturated fat diets, despite lower hepatic LCAT, apo A-I, and SR-B1
      mRNA abundance, suggesting that changes in available substrate and/or
      modification to the LCAT protein may have been involved in lipoprotein changes.
      These results suggest that lower HDL cholesterol concentrations, as a result of
      canola and soybean oil feeding, may not be detrimental due to increases in
      components involved in the reverse cholesterol transport process in these
      hamsters and may retard the progression of atherosclerosis.

PMID- 15735084
TI  - (n-3) fatty acids reduce the release of prostaglandin E2 from bone but do not
      affect bone mass in obese (fa/fa) and lean Zucker rats.
AB  - Childhood obesity is prevalent and linked to the development of Type 2 diabetes
      mellitus (DM) and poor bone health. Some PUFA enhance bone mass and thus may
      improve bone health in obese children. The study objective was to determine the
      effects of dietary (n-6) compared with (n-3) essential PUFA and long-chain PUFA
      (LCPUFA) on bone in an obese and insulin-resistant state. Male fa/fa (n = 48) and
      lean Zucker rats (n = 48) were fed diets containing safflower oil [SO, high (n-6)
      PUFA], flaxseed oil [FXO, high (n-3) PUFA], or menhaden oil [MO, high (n-3)
      LCPUFA] for 9 wk. Measurements included the following: femur bone area (BA),
      mineral content (BMC), density (BMD), morphometry and ex vivo release of
      prostaglandin E(2) (PGE(2)); plasma osteocalcin and C-terminal telopeptides of
      type I collagen. Differences among groups were detected using 2-way ANOVA.
      Genotype effects in the fa/fa rats included lower femoral weight, length, BA, and
      BMC, as well as femoral head and proximal epiphysis widths compared with the lean
      rats, but BMD was not affected. Femur BA, BMC, and BMD did not differ among the
      dietary groups, but diaphysis width was elevated in the MO group and PGE(2)
      release was reduced by the FXO and MO diets. No genotype x diet interactions were
      observed. These data indicate that the fa/fa Zucker rat is at risk for low bone
      mass and that dietary (n-3) FA effectively reduce PGE(2) release. Whether reduced
      PGE(2) will support optimal peak bone mass during childhood and conserve bone
      mass with aging warrants investigation.

PMID- 15735085
TI  - Low levels of dietary arachidonic and docosahexaenoic acids improve bone mass in
      neonatal piglets, but higher levels provide no benefit.
AB  - In piglets, feeding arachidonic acid (AA) and docosahexaenoic acid (DHA) in a 5:1
      ratio leads to elevated bone mass, but the optimal total quantity requires
      clarification. We studied bone mass and modeling of piglets that were randomized
      to receive 1 of 4 formulas for 15 d: control formula or the same formula with
      various levels of AA:DHA (0.5:0.1 g, 1.0:0.2 g or 2.0:0.4 g AA:DHA/100 g of fat).
      Measurements included: bone area (BA), mineral content (BMC), and density (BMD)
      of whole body, lumbar spine, and excised femurs; biomarkers of bone modeling were
      plasma osteocalcin and urinary cross-linked N-telopeptides of type 1 collagen
      (NTx), tibial ex vivo release of prostaglandin E(2) (PGE(2)), plasma insulin-like
      growth factor-1 (IGF-1), and tissue fatty acids. Main effects were identified
      using ANOVA and post hoc Bonferroni t tests. In supplemented piglets, relations
      among liver fatty acid proportions and bone mass were assessed using Pearson
      correlations. Whole body (P = 0.028) and lumbar spine (P = 0.043) BMD were higher
      in the group supplemented with 0.5:0.1 g AA:DHA/100 g of fat than in controls.
      Tissue AA and DHA increased in proportion to diet levels. Liver eicosapentaenoic
      acid (EPA) correlated positively (r > or = 0.38, P < or = 0.05) with whole body
      and femur BMC and BMD and lumbar spine BMC. Liver AA:EPA ratio correlated
      negatively (r > or = -0.039, P < or = 0.05) with whole body, femur, and lumbar
      spine BMC plus whole body and femur BMD. Dietary 1.0:0.2 g AA:DHA/100 g reduced
      NTx relative to 2.0:0.4 g AA:DHA/100 g of fat (P = 0.039). The diets did not
      affect the other biochemical variables measured. Low levels of dietary AA:DHA
      (0.5:0.1 g/100 g of fat) elevate bone mass, but higher amounts are not
      beneficial.

PMID- 15735086
TI  - Single-cell protein diet of a novel recombinant vitellogenin yeast enhances
      growth and survival of first-feeding tilapia (Oreochromis mossambicus) larvae.
AB  - Yeast single-cell protein (SCP) is a high-nutrient feed substitute. This study
      evaluates the dual applications of a novel recombinant Pichia pastoris SMD1168H
      (SMD) yeast, expressing a tilapia vitellogenin protein (rVtg), as an SCP diet for
      Artemia and the first-feeding fish larvae. Instar II Artemia fed rVtg, rVtg
      precultured in 5% fish oil (rVtg-FO), Saccharomyces cerevisiae (SC), or native
      SMD had greater lipid contents (P < 0.05) than the freshly hatched. Lipid
      deposition in the Artemia fed rVtg or rVtg-FO was greater (P < 0.05) than in
      those fed SMD or SC. Diet-induced accumulation of low levels of docosahexaenoic
      acid [22:6(n-3)] was detected only in Artemia fed the rVtg-based diets. Tilapia
      (Oreochromis mossambicus) larvae were fed solely yeast diets singly or in
      combination (d 3-22), or a staggered regimen of yeast (d 3-12) followed by
      unenriched or yeast-enriched Artemia (d 13-22). The larvae fed rVtg for 22 d
      increased in length and weight (P < 0.05), whereas those fed SC or SMD suffered
      growth suppression and high mortality. Such adverse consequences were ameliorated
      when 50% of SC was substituted with rVtg. The larvae prefed rVtg followed by a
      dietary switch to Artemia preenriched for 48 h with rVtg or rVtg-FO were greatest
      in length, had the highest weight gain, and lived the longest. Besides delivering
      rVtg protein, essential fatty acids and amino acids, rVtg may have probiotic
      effects in enhancing larval survival. This study suggests the feasibility of
      using the rVtg yeast as an Artemia booster and an SCP first feed for larvae.

PMID- 15735087
TI  - A comparison of the effects of betaine and S-adenosylmethionine on ethanol
      induced changes in methionine metabolism and steatosis in rat hepatocytes.
AB  - Previous studies showed that chronic ethanol administration alters methionine
      metabolism in the liver, resulting in increased intracellular S
      adenosylhomocysteine (SAH) levels and increased homocysteine release into the
      plasma. We showed further that these changes appear to be reversed by betaine
      administration. This study compared the effects of betaine and S
      adenosylmethionine (SAM), another methylating agent, on ethanol-induced changes
      of methionine metabolism and hepatic steatosis. Wistar rats were fed ethanol or
      control Lieber-Decarli liquid diet for 4 wk and metabolites of the methionine
      cycle were measured in isolated hepatocytes. Hepatocytes from ethanol-fed rats
      had a 50% lower intracellular SAM:SAH ratio and almost 2-fold greater
      homocysteine release into the media compared with controls. Supplementation of
      betaine or SAM in the incubation media increased this ratio in hepatocytes from
      both control and ethanol-fed rats and attenuated the ethanol-induced increased
      hepatocellular triglyceride levels by approximately 20%. On the other hand, only
      betaine prevented the increase in generation of homocysteine in the incubation
      media under basal and methionine-loaded conditions. SAM can correct only the
      ratio and the methylation defects and may in fact be detrimental after prolonged
      use because of its propensity to increase homocysteine release. Both SAM and
      betaine are effective in increasing the SAM:SAH ratio in hepatocytes and in
      attenuating hepatic steatosis; however, only betaine can effectively methylate
      homocysteine and prevent increased homocysteine release by the liver.

PMID- 15735088
TI  - Low concentrations of flavonoids are protective in rat H4IIE cells whereas high
      concentrations cause DNA damage and apoptosis.
AB  - Dietary flavonoids possess a wide spectrum of biochemical and pharmacological
      actions and are assumed to protect human health. These actions, however, can be
      antagonistic, and some health claims are mutually exclusive. The antiapoptotic
      actions of flavonoids may protect against neurodegenerative diseases, whereas
      their proapoptotic actions could be used for cancer chemotherapy. This study was
      undertaken to determine whether a cytoprotective dose range of flavonoids could
      be differentiated from a cytotoxic dose range. Seven structurally related
      flavonoids were tested for their ability to protect H4IIE rat hepatoma cells
      against H(2)O(2)-induced damage on the one hand and to induce cellular damage on
      their own on the other hand. All flavonoids proved to be good antioxidants in a
      cell-free assay. However, their pharmacologic activity did not correlate with in
      vitro antioxidant potential but rather with cellular uptake. For quercetin and
      fisetin, which were readily taken up into the cells, protective effects against
      H(2)O(2)-induced cytotoxicity, DNA strand breaks, and apoptosis were detected at
      concentrations as low as 10-25 micromol/L. On the other hand, these flavonoids
      induced cytotoxicity, DNA strand breaks, oligonucleosomal DNA fragmentation, and
      caspase activation at concentrations between 50 and 250 micromol/L. Published
      data on quercetin pharmacokinetics in humans suggest that a dietary supplement of
      1-2 g of quercetin may result in plasma concentrations between 10 and 50
      micromol/L. Our data suggest that cytoprotective concentrations of some
      flavonoids are lower by a factor of 5-10 than their DNA-damaging and proapoptotic
      concentrations.

PMID- 15735089
TI  - Proline-rich proteins moderate the inhibitory effect of tea on iron absorption in
      rats.
AB  - Tea inhibits iron absorption in studies in which tea is given with radiolabeled
      iron to humans as a single dose. Our objective was to test the hypothesis that
      proline-rich proteins (PRPs) may act as a defense against this effect by forming
      complexes with tannins, thereby preventing them from inhibiting iron absorption.
      Two studies were conducted. In study 1, rats were given test solutions containing
      (59)FeCl(3) in water, tea, or tea + gelatin (T/G). In study 2, the rats were
      divided into 3 groups and assigned to one of 3 nutritionally complete diets:
      control, tea (5 g tea tannin/kg diet), or T/G (5 g tea tannin + 60 g gelatin/kg
      diet). Rats were fed the respective diets for 5 d and then given a single (59)Fe
      labeled meal of the diet. Iron absorption was measured by whole-body retention of
      the (59)Fe over a 2-wk period. Iron absorption in study 1 was lower in the tea
      group (24 +/- 9.6%, P < 0.05) than in the T/G (42 +/- 19.4%) or water groups (50
      +/- 7.5%). In study 2, iron absorption did not differ among the groups. Rats fed
      the tea diet had dramatic hypertrophy of the parotid salivary glands. Adding
      gelatin as a proxy for salivary PRPs to the tea eliminated the inhibitory effect
      of tea on iron absorption. The results suggest that PRPs, whether from salivary
      glands or diet, can protect against the inhibition of iron absorption by tea.

PMID- 15735090
TI  - Allergic airway eosinophilia is suppressed in ovalbumin-sensitized Brown Norway
      rats fed raffinose and alpha-linked galactooligosaccharide.
AB  - We recently found that dietary raffinose suppressed allergic airway eosinophilia
      in ovalbumin-sensitized Brown Norway rats. Using this model in the present study,
      we compared the efficacy of other oligosaccharides with that of raffinose. Brown
      Norway rats were immunized s.c. with ovalbumin on d 0 and exposed to aerosolized
      ovalbumin on d 20; broncho-alveolar lavage fluid was obtained on d 21. In Expt.
      1, rats were fed a control diet or diets supplemented with different
      oligosaccharides (50 g/kg diet, raffinose, alpha-linked galactooligosaccharide,
      fructooligosaccharide, and xylooligosaccharide). The number of eosinophils in the
      fluid was significantly lower in rats fed raffinose and alpha-linked
      galactooligosaccharide diets than in those fed the control diet. Dietary
      fructooligosaccharide and xylooligosaccharide did not affect airway eosinophilia.
      In Expt. 2, i.p. administration of raffinose and alpha-linked
      galactooligosaccharide, but not fructooligosaccharide and xylooligosaccharide,
      suppressed airway eosinophilia in rats fed the control diet. In Expt. 3,
      suppression of airway eosinophilia by dietary alpha-linked galactooligosaccharide
      occurred in cecectomized rats administered neomycin. Reduced levels of
      interleukin (IL)-4 and IL-5 mRNA in lung tissue were associated with the
      suppression of airway eosinophilia. We propose that indigestible oligosaccharides
      differ in their suppressive effect on allergic airway eosinophilia in ovalbumin
      sensitized Brown Norway rats and that the effect appears not to be mediated by
      intestinal microflora.

PMID- 15735091
TI  - Folic acid supplementation can reduce the endothelial damage in rat brain
      microvasculature due to hyperhomocysteinemia.
AB  - To evaluate the effects of dietary folic acid supplementation on the cerebral
      vascular damage induced by hyperhomocysteinemia, rats were fed a diet containing
      3.0 g/kg homocystine for 2 wk and then either 3.0 g/kg homocystine or 3.0 g/kg
      homocystine plus 0.008 g/kg folic acid for 8 wk. Control rats consumed the AIN-93
      Maintenance diet throughout the experiment. The cerebral expression of glucose
      transporter-1 was measured by Western blot analysis and cerebrovascular
      structural alterations were evaluated by electron microscopy. The homocystine
      diet significantly increased the plasma levels of homocysteine and TBARS and
      decreased the cerebral expression of glucose transporter-1 (GLUT-1) with a
      concomitant increase in the percentage of damaged cerebral vessels. The inclusion
      of dietary folic acid for 8 wk caused plasma homocysteine levels to be the same
      as in control rats and it significantly upregulated the cerebral expression of
      GLUT-1 that was significantly reduced by hyperhomocysteinemia. Folic acid
      supplementation also significantly decreased the incidence of damaged vessels due
      to hyperhomocysteinemia. These results and the electron microscopy findings
      suggested that folic acid supplementation might reduce the detrimental effects on
      the endothelium caused by experimentally induced hyperhomocysteinemia.

PMID- 15735092
TI  - Chronic administration of docosahexaenoic acid ameliorates the impairment of
      spatial cognition learning ability in amyloid beta-infused rats.
AB  - We investigated whether administration of docosahexaenoic acid (DHA), a major (n
      3) fatty acid of the brain, ameliorates the impairment of learning ability in an
      animal model of Alzheimer's disease (AD), rats infused with amyloid-beta (Abeta)
      peptide (1-40) into the cerebral ventricle. Inbred 3rd generation male rats (20
      wk old) fed a fish oil-deficient diet were randomly divided into 4 groups: a
      vehicle group, an Abeta peptide-infused group (Abeta group), a DHA group, and an
      Abeta + DHA group. A mini-osmotic pump filled with Abeta peptide or vehicle was
      implanted in the rats, and they were tested for learning ability-related
      reference and working memory in an 8-arm radial maze. The rats were then orally
      fed DHA dissolved in 5% gum Arabic solution at 300 mg/(kg . d) (DHA and Abeta +
      DHA groups) or vehicle alone (vehicle and Abeta groups) and tested again for
      learning ability. DHA administered for 12 wk significantly reduced the increase
      in the number of reference and working memory errors in the Abeta-infused rats,
      and increased both the cortico-hippocampal level of DHA and the molar ratio of
      DHA/arachidonic acid, suggesting an amelioration of the impaired spatial
      cognition learning ability. Furthermore, DHA suppressed the increases in the
      levels of lipid peroxide and reactive oxygen species in the cerebral cortex and
      the hippocampus of Abeta-infused rats, suggesting that DHA increases
      antioxidative defenses. DHA is thus a possible therapeutic agent for ameliorating
      learning deficiencies due to Alzheimer's disease.

PMID- 15735093
TI  - The combination of high fruit and vegetable and low saturated fat intakes is more
      protective against mortality in aging men than is either alone: the Baltimore
      Longitudinal Study of Aging.
AB  - Saturated fat (SF) intake contributes to the risk of coronary heart disease (CHD)
      mortality. Recently, the protective effects of fruit and vegetable (FV) intake on
      both CHD and all-cause mortality were documented. However, individuals consuming
      more FV may be displacing higher-fat foods. Therefore, we investigated the
      individual and combined effects of FV and SF consumption on total and CHD
      mortality among 501 initially healthy men in the Baltimore Longitudinal Study of
      Aging (BLSA). Over a mean 18 y of follow-up, 7-d diet records were taken at 1-7
      visits. Cause of death was ascertained from death certificates, hospital records,
      and autopsy data. After adjustment for age, total energy intake, BMI, smoking,
      alcohol use, dietary supplements, and physical activity score, FV and SF intakes
      were individually associated with lower all-cause and CHD mortality (P < 0.05).
      When both FV and SF were included in the same model, associations of each were
      attenuated with CHD mortality, and no longer significant for all-cause mortality.
      Men consuming the combination of > or =5 servings of FV/d and < or =12% energy
      from SF were 31% less likely to die of any cause (P < 0.05), and 76% less likely
      to die from CHD (P < 0.001), relative to those consuming < 5 FV and >12% SF. Men
      consuming either low SF or high FV, but not both, did not have a significantly
      lower risk of total mortality; but did have 64-67% lower risk of CHD mortality (P
      < 0.05) relative to those doing neither. These results confirm the protective
      effects of low SF and high FV intake against CHD mortality. In addition, they
      extend these findings by demonstrating that the combination of both behaviors is
      more protective than either alone, suggesting that their beneficial effects are
      mediated by different mechanisms.

PMID- 15735094
TI  - Consumption of trans fatty acids is related to plasma biomarkers of inflammation
      and endothelial dysfunction.
AB  - Trans fatty acid intake has been associated with a higher risk of cardiovascular
      disease. The relation is explained only partially by the adverse effect of these
      fatty acids on the lipid profile. We examined whether trans fatty acid intake
      could also affect biomarkers of inflammation and endothelial dysfunction
      including C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis
      factor receptor 2 (sTNFR-2), E-selectin, and soluble cell adhesion molecules
      (sICAM-1 and sVCAM-1). We conducted a cross-sectional study of 730 women from the
      Nurses' Health Study I cohort, aged 43-69 y, free of cardiovascular disease,
      cancer, and diabetes at time of blood draw (1989-1990). Dietary intake was
      assessed by a validated FFQ in 1986 and 1990. CRP levels were 73% higher among
      those in the highest quintile of trans fat intake, compared with the lowest
      quintile. IL-6 levels were 17% higher, sTNFR-2 5%, E-selectin 20%, sICAM-1 10%,
      and sVCAM-1 levels 10% higher. Trans fatty acid intake was positively related to
      plasma concentration of CRP (P = 0.009), sTNFR-2 (P = 0.002), E-selectin (P =
      0.003), sICAM-1 (P = 0.007), and sVCAM-1 (P = 0.001) in linear regression models
      after controlling for age, BMI, physical activity, smoking status, alcohol
      consumption, intake of monounsaturated, polyunsaturated, and saturated fatty
      acids, and postmenopausal hormone therapy. In conclusion, this study suggests
      that higher intake of trans fatty acids could adversely affect endothelial
      function, which might partially explain why the positive relation between trans
      fat and cardiovascular risk is greater than one would predict based solely on its
      adverse effects on lipids.

PMID- 15735095
TI  - Population determinants of serum lycopene concentrations in the United States:
      data from the Third National Health and Nutrition Examination Survey, 1988-1994.
AB  - Serum lycopene is inversely related to the risk for cancer and cardiovascular
      diseases. We used data from the Third National Health and Nutrition Examination
      Survey, 1988-1994, to investigate the relation between serum lycopene
      concentrations and sex, age, geographical location, race-ethnicity, education,
      alcohol, smoking, BMI, blood pressure, serum total cholesterol and
      triacylglycerol, and intakes of fat, tomatoes and tomato-based products in 3413
      individuals aged 17-90 y. Multivariate adjusted mean lycopene concentrations were
      48.3% lower in individuals > or =70 y old than in those 17 to <30 y old (P <
      0.0001), 7.6% lower in women than in men (P = 0.0045), 15.1% lower in people
      living in the South than those in the West (P < 0.0001), 10.3 and 61.0% lower in
      the 1st quartile than in the 4th quartile for dietary fat intake (P = 0.0173) and
      serum cholesterol (P < 0.0001), respectively, 11.1% lower in tomato noneaters
      than those who ate tomatoes > or =31 times/mo (P = 0.0085), 13.5% lower in pizza
      noneaters than those who ate pizza > or =16 times/mo (P = 0.0016), and 20.6%
      lower in pasta noneaters than those who ate pasta (with tomato sauce) > or =16
      times/mo (P < 0.0001). Race-ethnicity, alcohol, BMI, blood pressure, and
      consumption of non-tomato vegetables, and fruits and juices had no association
      with serum lycopene concentrations. Sex, age, geographical region, socioeconomic
      status, serum total cholesterol, smoking, and intakes of fat, tomatoes, pizza,
      and pasta were significant determinants of serum lycopene concentrations in the
      United States.

PMID- 15735096
TI  - Dietary evaluation and attenuation of relative risk: multiple comparisons between
      blood and urinary biomarkers, food frequency, and 24-hour recall questionnaires:
      the DEARR study.
AB  - Estimates of diet-disease relative risks (RRs) suffer from inaccuracies
      introduced by dietary measurement errors. Using the "method of triads," by which
      the validity coefficient (VC) of the dietary assessment method and "true" long
      term intake could be estimated from 3 pairwise correlations between the FFQ, the
      reference method, and the biomarker, the authors evaluated the performance of a
      newly developed FFQ. Over a period of 13 mo (September 2000 to September 2001),
      161 participants completed 3 FFQs and six 24-h recalls (24HRs), and supplied 2
      blood samples and three 24-h urine collections. For protein, beta-carotene, and
      folic acid, the VCs of the FFQ with the "true intake" (0.77, 0.65, and 0.72,
      respectively) were relatively higher than the VCs of 24HRs (0.68, 0.60 and 0.39,
      respectively). Among the biomarkers, the VCs of serum beta-carotene and folic
      acid with the "true intake" (0.65 and 0.65) were higher than the VCs of urinary
      nitrogen and alpha-tocopherol (0.44 and 0.34, respectively). The DEARR study
      showed that the newly developed FFQ is a valid and reproducible instrument for
      assessing dietary intake. The VCs obtained can be used for future adjustment of
      diet-disease RR estimates in this population.

PMID- 15735097
TI  - Whole-grain rye bread consumption by women correlates with plasma
      alkylresorcinols and increases their concentration compared with low-fiber wheat
      bread.
AB  - Whole-grain rye and wheat products are rich in lignans, the precursors of
      enterolactone (ENL) and alkylresorcinols (ARs), which are phenolic lipids. In
      this crossover trial, we examined the effect of whole-grain rye bread compared
      with low-fiber wheat bread on plasma AR levels. Women (n = 39) aged 59 +/- 0.94 y
      (mean +/- SEM) were advised to consume rye (214 +/- 7.1 g/d) or wheat (178 +/-
      6.5 g/d) bread (20% of total daily energy intake) in random order for 8 wk. The
      test periods were separated by an 8-wk washout period. ARs with different
      homologues and ENL were measured in plasma collected at the beginning (habitual
      diet) and end of the test bread periods. AR concentrations were higher (P <
      0.001) after the rye bread (352 +/- 24.7 nmol/L) and habitual diet (97.7 +/- 12.1
      and 88.3 +/- 8.7 nmol/L) periods than after the wheat bread period (36.6 +/- 4.2
      nmol/L). Plasma AR concentrations were correlated with intake of rye bread (r =
      0.34, P = 0.037), and with insoluble fiber from the whole diet during the rye (r
      = 0.39, P = 0.013) and wheat (r = 0.32, P = 0.047) bread periods. The plasma AR
      17:0/21:0 ratio differed after the rye (0.84 +/- 0.04) and wheat (0.53 +/- 0.08)
      bread diet periods (P < 0.001). These data strongly suggest that plasma ARs could
      be used as specific biomarkers for whole-grain rye intake, and their homologue
      pattern could be used as an indicator of the bread type consumed.

PMID- 15735098
TI  - Soy protein isolates of varying isoflavone content exert minor effects on serum
      reproductive hormones in healthy young men.
AB  - Inverse associations between soy and prostate cancer and the contribution of
      hormones to prostate cancer prompted the current study to determine whether soy
      protein could alter serum hormones in men. Thirty-five men consumed milk protein
      isolate (MPI), low-isoflavone soy protein isolate (SPI) (low-iso SPI; 1.64 +/-
      0.19 mg isoflavones/d), and high-iso SPI (61.7 +/- 7.35 mg isoflavones/d) for 57
      d each in a randomized crossover design. Twenty-four-hour urine samples indicated
      that urinary isoflavones were significantly increased by the high-iso SPI
      relative to the low-iso SPI and MPI. Serum collected on d 1, 29, and 57 of each
      treatment revealed that dihydrotestosterone (DHT) and DHT/testosterone were
      significantly decreased by the low-iso SPI [9.4% (P = 0.036) and 9.0% (P =
      0.004), respectively] and the high-iso SPI [15% (P = 0.047) and 14% (P = 0.013),
      respectively], compared with the MPI at d 57. Other significant effects included
      a decrease in testosterone by the low-iso SPI relative to the MPI (P = 0.023) and
      high-iso SPI (P = 0.020) at d 29; an increase in dehydroepiandrosterone sulfate
      by the low-iso SPI relative to the MPI at d 29 (P = 0.001) and relative to the
      MPI (P = 0.0003) and high-iso SPI (P = 0.005) at d 57; and increases in estradiol
      and estrone by the low-iso SPI relative to the MPI at d 57 (P = 0.010 and P =
      0.005, respectively). In conclusion, soy protein, regardless of isoflavone
      content, decreased DHT and DHT/testosterone with minor effects on other hormones,
      providing evidence for some effects of soy protein on hormones. The relevance of
      the magnitude of these effects to future prostate cancer risk requires further
      investigation.

PMID- 15735099
TI  - Dietary intake of lycopene is associated with reduced pancreatic cancer risk.
AB  - Although fruits and vegetables have been implicated in the etiology of pancreatic
      cancer, the role of phytochemicals in these food groups has received little
      attention to date. In this study, we investigated the possible association
      between dietary carotenoids and pancreatic cancer risk. A case-control study of
      462 histologically confirmed pancreatic cancer cases and 4721 population-based
      controls in 8 Canadian provinces took place between 1994 and 1997. Dietary intake
      was assessed by a self-administered FFQ. Unconditional logistic regression was
      used to assess associations between specific and total carotenoid intakes and the
      risk of pancreatic cancer. All tests of statistical significance were 2-sided.
      After adjustment for age, province, BMI, smoking, educational attainment, dietary
      folate, and total energy intake, lycopene, provided mainly by tomatoes, was
      associated with a 31% reduction in pancreatic cancer risk among men [odds ratio
      (OR) = 0.69; 95% CI: 0.46-0.96; P = 0.026 for trend] when comparing the highest
      and lowest quartiles of intake. Both beta-carotene (OR = 0.57; 95% CI: 0.32-0.99;
      P = 0.016 for trend) and total carotenoids (OR = 0.58; 95% CI: 0.34-1.00; P =
      0.02 for trend) were associated with a significantly reduced risk among those who
      never smoked. The results of this study suggest that a diet rich in tomatoes and
      tomato-based products with high lycopene content may help reduce pancreatic
      cancer risk.

PMID- 15735100
TI  - Lignans are involved in the antitumor activity of wheat bran in colon cancer
      SW480 cells.
AB  - Wheat bran was shown to provide protection against colorectal cancer in human
      intervention and animal studies. Our recent study showed, however, that antitumor
      activities of wheat bran from various wheat cultivars differed significantly even
      when wheat fiber was equal in diets. We hypothesized that phytochemical lignans
      in wheat bran may account for the differences among wheat cultivars in cancer
      prevention. The concentration of a major lignan, secoisolariciresinol
      diglycoside, was determined by HPLC in 4 selected wheat cultivars (i.e., Madison,
      Ernie, Betty, and Arapahoe). The lignan concentrations and their antitumor
      activities, previously determined in APC-Min mice, were correlated (r = 0.73, P <
      0.02). The cancer preventive mechanisms of 2 prominent lignan metabolites
      (enterolactone and enterodiol) were further studied in human colonic cancer SW480
      cells. Treatment with enterolactone and enterodiol, alone or in combination, at 0
      40 micromol/L resulted in dose- and time-dependent decreases in cell numbers.
      Although the cytotoxicity as measured by trypan blue staining in adherent cells
      was not affected, DNA flow cytometric analysis indicated that the treatments
      induced cell cycle arrest at the S-phase. Western blot analysis for cyclin A, a
      required protein for S/G2 transition, showed that the cyclin A protein levels
      decreased after treatment with enterodiol or the combination of enterolactone and
      enterodiol at 40 micromol/L for 72 h. Apoptosis analysis by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling assay showed an
      increased percentage of apoptotic cells in the floating cells after enterodiol
      alone or combined treatments. These results suggest for the first time that
      lignans may contribute, at least in part, to the cancer prevention by wheat bran
      observed in APC-Min mice. Inhibition of cancer cell growth by lignan metabolites
      seems to be mediated by cytostatic and apoptotic mechanisms.

PMID- 15735101
TI  - The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in
      postmenopausal women depends on equol production status but is not influenced by
      probiotic consumption.
AB  - Some epidemiologic studies reported an association between a low ratio of urinary
      2-hydroxyestrogens (2-hydroxyestradiol + 2-hydroxyestrone) to 16alpha
      hydroxyestrone (2:16OHE(1)) and increased breast cancer risk. Some studies show
      that soy consumption increases this ratio, and it is suggested that this effect
      may reduce breast cancer risk. We hypothesized that consumption of probiotic
      bacteria would alter fecal bacteria and enzymes involved in soy isoflavone
      metabolism, thereby increasing isoflavone bioavailability and enhancing the
      beneficial effects of soy on estrogen metabolism. Breast cancer survivors (n =
      20) and controls (n = 20) were given 4 treatments for 6 wk each, separated by 2
      wk washout periods, in a randomized, crossover design: soy protein (26.6 +/- 4.5
      g protein/d containing 44.4 +/- 7.5 mg isoflavones/d); soy protein + probiotics
      (10(9) colony-forming units Lactobacillus acidophilus DDS(R)+1 & Bifidobacterium
      longum, 15-30 mg fructooligosaccharide/d); milk protein (26.6 +/- 4.5 g
      protein/d); and milk protein + probiotics. Survivors tended to have a lower
      baseline urine 2:16OHE(1) ratio than controls (P = 0.10). In the group as a
      whole, soy consumption tended to increase urinary 2-hydroxyestrogens (P = 0.07)
      and 16alpha-hydroxyestrone (P = 0.11) but had no effect on the urinary 2:16OHE(1)
      ratio. When subjects were divided into groups by plasma concentrations and
      urinary levels of the daidzein metabolite equol, soy increased urinary 2
      hydroxyestrogens (P = 0.01) and the 2:16OHE(1) ratio (P = 0.04) only in subjects
      with high plasma equol concentrations. None of these results were influenced by
      probiotic consumption. These results are consistent with studies that found lower
      urine 2:16OHE(1) ratios in women with breast cancer and suggest that soy
      consumption increases this ratio only in women who are equol producers.

PMID- 15735103
TI  - Measurement of 3-hydroxyisovaleric acid in urine of biotin-deficient infants and
      mice by HPLC.
AB  - We developed an assay for measuring urinary 3-hydroxyisovaleric acid (3-HIA)
      using HPLC after derivatization with 2-nitrophenylhydrazine hydrochloride (2-NPH
      . HCl). The derivatized 3-HIA was extracted into n-hexane and separated
      isocratically on a C8 reversed-phase column for fatty acids (YMC-Pack FA). We
      used this method to measure 3-HIA in urine extracts from mice fed a biotin
      deficient diet for >4 wk and in an infant who was fed a special Japanese formula
      and was suspected of being biotin deficient. Urinary 3-HIA could be assayed
      within the range of 0.42-8.5 mmol/L with high accuracy by this method, as an
      indicator of biotin deficiency. Therefore, the HPLC method for 3-HIA described
      here may be a useful tool clinically as well as in the research laboratory.

PMID- 15735102
TI  - Ellagic acid potentiates the effect of quercetin on p21waf1/cip1, p53, and MAP
      kinases without affecting intracellular generation of reactive oxygen species in
      vitro.
AB  - Anticarcinogenic effects attributed to polyphenols in fruits may be based on
      synergistic, additive, or antagonistic interactions of many compounds. In a
      previous study, it was demonstrated that quercetin and ellagic acid interacted
      synergistically in the induction of apoptosis in the human leukemia cell line,
      MOLT-4. To investigate possible cellular mechanisms, this study evaluated whether
      synergistic effects might be detectable within proapoptotic or antiproliferative
      signal transduction pathways. We found that quercetin and combinations of
      quercetin and ellagic acid nonsynergistically increased p53 protein levels. In
      contrast, ellagic acid potentiated the effects of quercetin for p21(cip1/waf1)
      protein levels and p53 phosphorylation at serine 15, possibly explaining the
      synergistic effect observed in apoptosis induction. Phosphorylation of the
      mitogen-activated protein (MAP) kinases, c-jun N-terminal (JNK)1,2 and p38, was
      also increased by the combination of ellagic acid and quercetin, whereas
      quercetin alone induced only p38. We further evaluated whether the generation of
      reactive oxygen species (ROS) and/or quercetin stability were influenced by
      interactions of ellagic acid with quercetin. Quercetin increased the generation
      of ROS, which was neither potentiated nor inhibited by ellagic acid. The
      stability of intracellular and extracellular quercetin was not influenced by the
      presence of ellagic acid. In summary, quercetin and ellagic acid combined
      increase the activation of p53 and p21(cip1/waf1) and the MAP kinases, JNK1,2 and
      p38, in a more than additive manner, suggesting a mechanism by which quercetin
      and ellagic acid synergistically induce apoptosis in cancer cells.

PMID- 15735104
TI  - Differential kinetic behavior and distribution for pteroylglutamic acid and
      reduced folates: a revised hypothesis of the primary site of PteGlu metabolism in
      humans.
AB  - Single (13)C(6)-labeled doses of pteroylmonoglutamic acid (PteGlu: 634 nmol; n =
      14), (6S-)5-formyltetrahydrofolic acid (431-569 nmol; n = 16), or [(15)N(1-7)]
      intrinsically labeled spinach (mainly 5-methyltetrahydrofolate) (588 nmol; n =
      14) were fed to fasting adult volunteers. Plasma-labeled 5-methyltetrahydrofolic
      acid responses were monitored for 8 h. There was a slower rate of increase in
      plasma-labeled 5-methyltetrahydrofolic acid and longer time to peak (171 +/- 9
      min; mean +/- SEM) following an oral dose of [(13)C(6)]PteGlu than either
      [(13)C(6)]5-formyltetrahydrofolic acid (54 +/- 10 min) or [(15)N(1-7)]spinach
      folate (60 +/- 13 min) suggesting saturated metabolic capacity for the
      biotransformation of PteGlu. Mathematical modeling generated a significantly
      higher mean "apparent absorption" for 5-formyltetrahydrofolic acid (38%) and
      spinach folate (44%) than for PteGlu (24%). The high "relative absorption" of
      reduced folates to PteGlu was unexpected given that PteGlu itself, from (14)C
      tracer mass balance experiments, is almost completely absorbed. Although it is
      ubiquitously accepted that a physiological dose of PteGlu is reduced and
      methylated in the epithelial cells of the small intestine, and that essentially
      only 5-methyltetrahydrofolic acid is exported into the hepatic portal vein (HPV),
      as is the case for absorbed reduced 1-carbon-substituted folates, modeling
      indicated greater liver sequestration when PteGlu was used as the test dose,
      suggesting that PteGlu enters the HPV unaltered and that the liver is the primary
      site of initial metabolism. Because of the observed differential plasma response
      and the hypothesized difference in the site of initial metabolism, the historical
      use of PteGlu as a "reference folate" in studies of folate bioavailability is
      seriously questioned.

PMID- 15735106
TI  - The International Research on Infant Supplementation initiative.
AB  - The International Research on Infant Supplementation trials emerged as an attempt
      to develop a credible evidence base to guide policy decision making in this area.
      The fact that infant diets in developing country settings are more often
      deficient in multiple micronutrients rather than in single nutrients and/or
      energy was increasingly recognized during the 1990s. The concept of a "foodlet,"
      a crushable hybrid between a tablet and a food that is water dispersible, was
      developed at the first IRIS meeting in Rio de Janeiro in 1999. Trials were
      performed in 4 countries: Indonesia, Peru, South Africa, and Vietnam. Four
      different formulations of foodlets were tested: a daily placebo supplement, a
      daily iron supplement, a daily multiple micronutrient supplement, and a weekly
      multiple micronutrient supplement with a placebo on the other 6 d. The multiple
      micronutrient foodlets contained adequate daily intakes of 13 micronutrients
      considered most likely to be inadequate in infant diets. The foodlets were
      produced in Peru and distributed to all 4 of the country study sites. The methods
      used in the efficacy trials were standardized across countries, and the trials
      were carried out in infants 6-11 mo of age for 6 mo. Anthropometry was measured
      monthly and morbidity checked daily. Blood samples were collected at baseline and
      at the end of the trial. The data and the biological samples collected in each
      country were analyzed centrally. The results of this remarkable international
      collaboration are encouraging and, hopefully, will spur the development of
      programs in this area of nutrition interventions.

PMID- 15735107
TI  - Efficacy of a foodlet-based multiple micronutrient supplement for preventing
      growth faltering, anemia, and micronutrient deficiency of infants: the four
      country IRIS trial pooled data analysis.
AB  - Diets of infants across the world are commonly deficient in multiple
      micronutrients during the period of growth faltering and dietary transition from
      milk to solid foods. A randomized placebo controlled trial was carried out in
      Indonesia, Peru, South Africa, and Vietnam, using a common protocol to
      investigate whether improving status for multiple micronutrients prevented growth
      faltering and anemia during infancy. The results of the pooled data analysis of
      the 4 countries for growth, anemia, and micronutrient status are reported. A
      total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a
      daily placebo (P), 283 receiving a weekly multiple micronutrient supplement
      (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288
      received daily iron (DI) supplements. The DMM group had a significantly greater
      weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for
      the WMM group, and 186 g/mo for the DI and P groups. There were no differences in
      height gain. DMM was also the most effective treatment for controlling anemia and
      iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin
      status. DI supplementation alone increased zinc deficiency. The prevalence of
      multiple micronutrient deficiencies at baseline was high, with anemia affecting
      the majority, and was not fully controlled even after 6 mo of supplementation.
      These positive results indicate the need for larger effectiveness trials to
      examine how to deliver supplements at the program scale and to estimate cost
      benefits. Consideration should also be given to increasing the dosages of
      micronutrients being delivered in the foodlets.

PMID- 15735108
TI  - Multiple micronutrient supplements improve micronutrient status and anemia but
      not growth and morbidity of Indonesian infants: a randomized, double-blind,
      placebo-controlled trial.
AB  - Multiple micronutrient deficiencies are highly prevalent in Indonesia, but the
      interventions are still focused on single micronutrients. This study aimed to
      investigate the efficacy of multiple micronutrient supplements for improving
      micronutrient status, anemia, growth, and morbidity of Indonesian infants. In
      this double-blind, placebo-controlled trial, 284 infants aged 6-12 mo were
      randomly allocated to 4 treatment groups for 23 wk; 260 (92%) infants completed
      the study. Group 1 (DMM) received one adequate intake of multiple micronutrient
      supplements daily (n = 66); group 2 (WMM) received 2 adequate intakes of multiple
      micronutrient on 1d plus 6 d of placebo (n = 60); group 3 (DI) received 10 mg of
      iron supplement daily (n = 69); group 4 received a placebo supplement daily (n =
      65). Blood samples were collected at baseline and at posttreatment to assess
      anemia and micronutrient status. Anthropometric measurements were taken monthly,
      and morbidity was recorded daily. At baseline, 58.1% of infants were anemic,
      34.2% were iron deficient, 21.3% were vitamin A deficient, and 11% were zinc
      deficient. The DMM and DI supplements both corrected iron deficiency, but DMM
      supplements were more efficacious in improving hemoglobin levels of anemic
      infants than the other supplements. However, anemia still persisted in one-third
      of DMM infants posttreatment. The DMM supplement was more efficacious than WMM or
      DI supplementation in improving infant status of other micronutrients, including
      zinc, tocopherol, and riboflavin, whereas DI exacerbated zinc deficiency. There
      were no significant differences in growth and morbidity among treatment groups,
      and growth faltering was not prevented.

PMID- 15735109
TI  - Efficacy of multiple micronutrient supplementation for improving anemia,
      micronutrient status, growth, and morbidity of Peruvian infants.
AB  - Anemia, micronutrient deficiencies, and growth faltering are still common in
      Peru. The study objective was to determine the efficacy of different
      micronutrient supplements in preventing growth failure, anemia, and micronutrient
      deficiencies in Peruvian infants. Three hundred and thirteen infants aged 6 to 12
      mo participated in a double-blind, masked, controlled trial in which they were
      randomly assigned to receive either a daily dose of iron (DI), a daily dose of
      multiple micronutrients (DMM), a weekly dose of multiple micronutrients, or a
      placebo (P) for 6 mo. None of the supplements tested prevented growth faltering
      or the morbidities common during infancy. Anemia and plasma homocysteine
      concentrations fell significantly in all groups during the study, but the mean
      change of plasma homocysteine during the trial period was significantly smaller
      in the DI group than in other groups, and the increase in hemoglobin
      concentrations was smaller in the P group than the micronutrient treatment
      groups. Plasma ferritin concentrations decreased least in the groups taking daily
      micronutrient supplements containing iron (DI and DMM). There were no significant
      differences among groups in mean final values or changes in plasma zinc, retinol,
      tocopherol, or riboflavin. Although the DMM intervention was the most efficacious
      for preventing anemia, iron, and zinc deficiencies, 15%, 20%, and 50% of this
      group still remained anemic, zinc deficient, and iron deficient, respectively, at
      the end of the study. Further research thus should investigate whether higher
      doses of iron and zinc, together with infection control measures, are more
      efficacious.

PMID- 15735110
TI  - Efficacy of multiple micronutrient supplementation for improving anemia,
      micronutrient status, and growth in South African infants.
AB  - Growth faltering, anemia, and multiple micronutrient deficiency are common during
      infancy in developing countries. This South African trial was part of a
      multicenter study aimed at testing the efficacy of multiple micronutrient
      supplementation on growth, anemia, micronutrient status, and morbidity during
      infancy across 4 countries. A total of 265 infants aged 6-12 mo were individually
      randomized to 1 of 4 intervention groups: a daily multiple micronutrient
      supplement (DMM), a daily placebo supplement (P); a multiple micronutrient
      supplement 1 d of the week and placebo supplement on the other days of the week
      (WMM), and a daily iron supplement (DI). For 6 mo, the blinded supplements were
      provided to mothers at monthly health clinic sessions, and consumption was
      verified during weekly household visits by community health workers, when
      morbidity was also checked. Weight and height of the infants were measured
      monthly, and blood samples were taken at the beginning and at the end for
      assessing the infants micronutrient status. There were no significant differences
      in nutritional status of the groups at baseline with 40% of infants with anemia
      (hemoglobin < 110 g/L), 16% vitamin A deficiency (plasma retinol < 0.7
      micromol/L), 47% zinc deficiency (plasma zinc < 10.7 micromol/L), 2% underweight,
      and 11% stunting. There was no difference in growth or morbidity between the
      micronutrient supplemented groups and the P group during the 6-mo study. The DMM
      was the most effective intervention tested, not only for improving anemia but
      also for improving iron, zinc, riboflavin, and tocopherol status.

PMID- 15735111
TI  - Multiple micronutrient supplementation improves anemia, micronutrient nutrient
      status, and growth of Vietnamese infants: double-blind, randomized, placebo
      controlled trial.
AB  - A randomized, double-blind, placebo-controlled trial was performed to assess the
      efficacy of different micronutrient supplementation regimes for improving
      micronutrient status, preventing anemia, and growth faltering of Vietnamese
      infants. A population-based sample of 306 infants aged 6-12 mo, split in 4
      treatment groups, received daily multiple micronutrient (DMM), daily placebo (P),
      weekly multiple micronutrient (WMM), or daily iron (DI) supplements for 6 mo, 7
      d/wk, under supervision. Weight and length were measured monthly, and anemia and
      plasma levels of ferritin, zinc, riboflavin, retinol, tocopherol, and
      homocysteine were determined before and after the supplementation. Z-scores for
      length-for-age and weight-for-age worsened significantly in all groups, but the
      length-for-age Z-score decreased significantly less in the DMM group (-0.32 +/-
      0.05) than in the P and WMM groups (-0.49 +/- 0.05 and -0.51 +/- 0.05,
      respectively, P = 0.001). Hemoglobin levels increased significantly more in the
      DMM group [mean (95%CI): 16.4 g/L (12.4-20.4)] than in the P group [8.6 g/L (5.0
      12.2), P = 0.04), with intermediate nonsignificant increases in the WMM [15.0 g/L
      (11.5-18.5)] and the DI [12.9 g/L (8.4-17.3)] groups. Ferritin changes were
      significantly greater in DMM (12.1 microg/L) and DI (9.5 microg/L) than in P (
      14.7 microg/L) and WMM groups (-9.7 microg/L). Of the other micronutrients, only
      tocopherol showed a significantly greater level in the DMM group compared with P.
      Anemia still affected a quarter and zinc deficiency affected a third of infants
      although there was no iron deficiency after 6 mo of supplementation with DMM,
      suggesting that multiple factors are causing anemia and that the dose of zinc is
      too small.

PMID- 15735112
TI  - The International Research on Infant Supplementation study: implications for
      programs and further research.

PMID- 15735113
TI  - Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in
      normal tissue as predictors of fluorouracil sensitivity.
AB  - PURPOSE: To analyze thymidylate synthase (TS) and methylenetetrahydrofolate
      reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU)
      sensitivity. PATIENTS AND METHODS: The study included a retrospective analysis of
      88 patients with metastatic colorectal cancer and a prospective trial with 51
      patients also with measurable metastases. All patients were treated with FU and
      leucovorin. The analysis of gene polymorphism was performed on normal intestinal
      tissue and lymphocytes. RESULTS: The response rate was significantly higher in
      patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other
      groups. The difference of response rate translated to a difference in time to
      progression. Similar results were observed in the retrospective analysis and the
      prospective confirmatory trial. CONCLUSION: The analysis of gene polymorphism
      allows delineation of a group of patients (30%) with a response rate to a single
      drug of approximately 50%. This information should be used in the design of
      tailored treatment.

PMID- 15735114
TI  - Size of breast cancer metastases in axillary lymph nodes: clinical relevance of
      minimal lymph node involvement.
AB  - BACKGROUND: Overt ipsilateral axillary lymph node metastases of breast cancer are
      the most significant prognostic indicators for women who have undergone surgery,
      yet the clinical relevance of minimal involvement (isolated tumor cells and
      micrometastases) of these nodes is uncertain. PATIENTS AND METHODS: We evaluated
      biologic features, adjuvant treatment recommendations, and prognosis for 1,959
      consecutive patients with pT1-3, pN0, minimal lymph node involvement (pN1mi or
      pN0i+), or pN1a (single positive node) and M0, who were operated on and counseled
      for medical therapy from April 1997 to December 2000. RESULTS: Patients with pN1a
      and pN1mi/pN0i+, when compared with patients with pN0 disease, were more often
      prescribed anthracycline-containing chemotherapy (39.1% v 33.2% v 6.1%,
      respectively; P < .0001) and were less likely to receive endocrine therapy alone
      (9.8% v 19.4% v 41.9%, respectively; P < .0001). At the multivariate analysis, a
      statistically significant difference in disease-free survival (DFS) and in the
      risk of distant metastases was observed for patients with pN1a versus pN0 disease
      (hazard ratio [HR] = 2.04; 95% CI, 1.46 to 2.86; P < .0001 for DFS; HR = 2.32;
      95% CI, 1.42 to 3.80; P = .0007 for distant metastases) and for patients with
      pN1mi/pN0i+ versus pN0 disease (HR = 1.58; 95% CI, 1.01 to 2.47; P = .047 for
      DFS; HR = 1.94; 95% CI, 1.04 to 3.64; P = .037 for distant metastases).
      CONCLUSION: Even minimal involvement of a single axillary node in breast cancer
      significantly correlates with worse prognosis compared with no axillary node
      involvement. Further studies are required before widespread modification of
      clinical practice.

PMID- 15735115
TI  - Site of primary tumor has a prognostic role in operable breast cancer: the
      international breast cancer study group experience.
AB  - PURPOSE: Cancer presenting at the medial site of the breast may have a worse
      prognosis compared with tumors located in external quadrants. For medial tumors,
      axillary lymph node staging may not accurately reflect the metastatic potential
      of the disease. PATIENTS AND METHODS: Eight-thousand four-hundred twenty-two
      patients randomly assigned to International Breast Cancer Study Group clinical
      trials between 1978 and 1999 were classified as medial site (1,622; 19%) or
      lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years.
      RESULTS: A statistically significant difference was observed for patients with
      medial tumors versus those with nonmedial tumors in disease-free survival (DFS;
      10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall
      survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference
      increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13
      to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The
      risk of relapse for patients with medial presentation was largest for the node
      negative cohort and for patients with tumors larger than 2 cm. In the subgroup of
      2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and
      OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95%
      CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003
      for OS). CONCLUSION: Tumor site has a significant prognostic utility, especially
      for axillary lymph node-negative disease, that should be considered in
      therapeutic algorithms. New staging procedures such as biopsy of the sentinel
      internal mammary nodes or novel imaging methods should be further studied in
      patients with medial tumors.

PMID- 15735116
TI  - Gemcitabine, epirubicin, and paclitaxel versus fluorouracil, epirubicin, and
      cyclophosphamide as first-line chemotherapy in metastatic breast cancer: a
      Central European Cooperative Oncology Group International, multicenter,
      prospective, randomized phase III trial.
AB  - BACKGROUND: The objectives of this phase III trial were to compare the time to
      progressive disease (TtPD), overall response rate (ORR), overall survival, and
      toxicity of gemcitabine, epirubicin, and paclitaxel (GET) versus fluorouracil
      (FU), epirubicin, and cyclophosphamide (FEC) as first-line therapy in patients
      with metastatic breast cancer (MBC). PATIENTS AND METHODS: Female patients aged
      18 to 75 years with stage IV and measurable MBC were enrolled and randomly
      assigned to either gemcitabine (1,000 mg/m(2), days 1 and 4), epirubicin (90
      mg/m(2), day 1), and paclitaxel (175 mg/m(2), day 1) or FU (500 mg/m(2), day 1),
      epirubicin (90 mg/m(2), day 1), and cyclophosphamide (500 mg/m(2), day 1). Both
      regimens were administered every 21 days for a maximum of eight cycles. RESULTS:
      Between October 1999 and November 2002, 259 patients (GET, n = 124; FEC, n = 135)
      were enrolled. Baseline characteristics were well balanced across treatment arms.
      After a median of 20.4 months of follow-up, median TtPD was 9.1 months and 9.0
      months in the GET and FEC arms, respectively (P = .557). The ORR was 62.3% in the
      GET arm (n = 114) and 51.2% in the FEC arm (n = 129; P = .093). Grade 3 and 4
      toxicities, including neutropenia, thrombocytopenia, anemia, stomatitis,
      neurosensory toxicity, and allergy, occurred significantly more often in the GET
      arm. CONCLUSION: No significant differences in terms of TtPD and ORR were
      observed between the two treatment arms. Treatment-related toxicity was higher in
      the GET arm.

PMID- 15735117
TI  - Postmastectomy radiation and mortality in women with T1-2 node-positive breast
      cancer.
AB  - PURPOSE: To determine the relationship between postmastectomy radiotherapy (PMRT)
      and mortality in a population-based cohort of women with T1-2 node-positive
      breast cancer. PATIENTS AND METHODS: Using data from the Surveillance,
      Epidemiology, and End Results program, we identified 18,038 women with T1-2 node
      positive invasive breast cancer who were treated with mastectomy between 1988 and
      1995. The relationship between PMRT and mortality was determined using
      proportional hazards multivariate modeling and propensity score matched case
      control analysis. RESULTS: Median follow-up was 8.1 years. Only 2,648 women (15%)
      received PMRT. After adjusting for covariates, PMRT use was not associated with
      mortality (hazard ratio [HR] = 0.96; 95% CI, 0.90 to 1.03). However, the
      interaction term for PMRT use and number of involved regional lymph nodes was
      significant (P = .002), suggesting that, above a certain threshold of involved
      nodes, a mortality benefit from PMRT may exist. Adjusted analysis stratified by
      number of involved nodes revealed that patients with seven or more involved nodes
      treated with PMRT experienced a significant reduction in all-cause (HR = 0.84;
      95% CI, 0.76 to 0.93) and cause-specific mortality (HR = 0.86; 95% CI, 0.77 to
      0.96). Propensity score matched case-control analysis confirmed that PMRT was
      associated with reduced mortality only in the subset of patients with seven or
      more involved nodes (HR = 0.81; 95% CI, 0.73 to 0.91 for all-cause mortality; and
      HR = 0.82; 95% CI, 0.72 to 0.93 for cause-specific mortality). CONCLUSION: For
      women with T1-2 breast cancer, PMRT is associated with a 15% to 20% relative
      reduction in mortality for patients with seven or more involved regional lymph
      nodes.

PMID- 15735118
TI  - Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic
      breast cancer.
AB  - PURPOSE: Metastatic breast cancer (MBC) is incurable; its treatment is
      palliative. We investigated whether the presence of circulating tumor cells
      (CTCs) predicts treatment efficacy, progression-free survival (PFS), and overall
      survival (OS) in patients with newly diagnosed MBC who were about to start first
      line therapy. PATIENTS AND METHODS: One hundred seventy-seven patients with
      measurable MBC were enrolled onto a prospective study. Eighty-three of the 177
      patients were entering first-line treatment, and these patients are the focus of
      this analysis. CTCs from 7.5 mL of whole blood drawn before treatment initiation
      (baseline) and monthly thereafter for up to 6 months were isolated and enumerated
      using immunomagnetics. RESULTS: The mean (+/- standard deviation) follow-up time
      was 11.1 +/- 4.4 months (median, 12.2 months). Forty-three patients (52%) had >
      or = five CTCs at baseline. The median PFS was 7.2 months (95% CI, 4.9 to 9.4
      months), and the median OS was more than 18 months. Patients with > or = five
      CTCs at baseline and at first follow-up (4 weeks) had a worse prognosis than
      patients with less than five CTCs (baseline: median PFS, 4.9 v 9.5 months,
      respectively; log-rank, P = .0014; median OS, 14.2 v > 18 months, respectively;
      log-rank, P = .0048; first follow-up: median PFS, 2.1 v 8.9 months, respectively;
      log-rank, P = .0070; median OS, 11.1 v > 18 months, respectively; log-rank, P =
      .0029). CTCs before and after the initiation of therapy were strong, independent
      prognostic factors. CONCLUSION: Detection of CTCs before initiation of first-line
      therapy in patients with MBC is highly predictive of PFS and OS. This technology
      can aid in appropriate patient stratification and design of tailored treatments.

PMID- 15735119
TI  - Multi-institutional randomized phase II trial of the epothilone B analog
      ixabepilone (BMS-247550) with or without estramustine phosphate in patients with
      progressive castrate metastatic prostate cancer.
AB  - PURPOSE: To evaluate the antitumor activity and safety of the epothilone B
      analog, ixabepilone, with or without estramustine phosphate (EMP), in
      chemotherapy-naive patients with progressive castrate metastatic prostate cancer.
      PATIENTS AND METHODS: Patients were randomly assigned to receive ixabepilone (35
      mg/m(2)) by intravenous infusion every 3 weeks with or without EMP 280 mg orally
      three times daily on days 1 to 5. RESULTS: Between December 2001 and October
      2003, 92 patients were enrolled and randomly assigned to treatment with
      ixabepilone alone (45 patients) or in combination with EMP (47 patients). Grades
      3 and 4 toxicities experienced by more than 5% of patients included neutropenia
      (22%), fatigue (9%), and neuropathy (13%) on the ixabepilone arm, and neutropenia
      (29%), febrile neutropenia (9%), fatigue (9%), neuropathy (7%), and thrombosis
      (6%) on the ixabepilone + EMP arm. Post-treatment declines in prostate-specific
      antigen of > or = 50% were achieved in 21 of 44 patients (48%; 95% CI, 33% to
      64%) on the ixabepilone arm, and 31 of 45 patients (69%; 95% CI, 55% to 82%) on
      the ixabepilone + EMP arm. In patients with measurable disease, partial responses
      were observed in eight of 25 patients (32%; 95% CI, 14% to 50%) on the
      ixabepilone arm, and 11 of 23 (48%; 95% CI, 27% to 68%) on the ixabepilone + EMP
      arm. Time to prostate-specific antigen progression was 4.4 months (95% CI, 3.1 to
      6.9 months) on the ixabepilone-alone arm and 5.2 months (95% CI, 4.5 to 6.8
      months) on the combination arm. CONCLUSION: Ixabepilone, with or without
      estramustine phosphate, is well tolerated and has antitumor activity in patients
      with castrate metastatic prostate cancer.

PMID- 15735120
TI  - Supradose intra-arterial cisplatin and concurrent radiation therapy for the
      treatment of stage IV head and neck squamous cell carcinoma is feasible and
      efficacious in a multi-institutional setting: results of Radiation Therapy
      Oncology Group Trial 9615.
AB  - PURPOSE: To determine the feasibility of high-dose intra-arterial (IA) cisplatin
      and concurrent radiation therapy (RT) for head and neck squamous cell carcinoma
      in the multi-institutional setting (Multi-RADPLAT). PATIENTS AND METHODS:
      Eligibility included T4 squamous cell carcinoma of the oral cavity, oropharynx,
      hypopharynx, or larynx. Patients received cisplatin (150 mg/m(2) IA with sodium
      thiosulfate 9 g/m(2) intravenous [IV], followed by 12 g/m(2) IV over 6 hours,
      weekly for 4 weeks) and concurrent RT (70 Gy, 2.0 Gy/fraction, daily for 5 days
      over 7 weeks). Between May 1997 and December 1999, 67 patients from three
      experienced and eight inexperienced centers were enrolled, of whom 61 were
      eligible for analysis. RESULTS: Multi-RADPLAT was feasible (ie, three or four
      infusions of IA cisplatin and full dose of RT) in 53 patients (87%). The complete
      response (CR) rate was 85% at the primary site and 88% at nodal regions, and the
      overall CR rate was 80%. At a median follow-up of 3.9 years for alive patients
      (range, 0.9 to 6.1 years), the estimated 1-year and 2-year locoregional tumor
      control rates are 66% and 57%, respectively. The estimated 1-year and 2-year
      survival rates are 72% and 63%, respectively. The estimated 1-year and 2-year
      disease-free survival rates are 62% and 46%, respectively. The rates of grade 4
      and 5 toxicities at the experienced and the inexperienced institutions were 14%
      and 0% v 47% and 4%, respectively. CONCLUSION: This intensive treatment regimen
      for head and neck cancer is feasible and effective in a multi-institutional
      setting.

PMID- 15735121
TI  - Preoperative serum squamous cell carcinoma antigen levels in clinical decision
      making for patients with early-stage cervical cancer.
AB  - PURPOSE: To prevent morbidity associated with double modality treatment, early
      stage cervical cancer patients should only be offered surgery when there is a low
      likelihood for adjuvant radiotherapy. We analyzed whether serum squamous cell
      carcinoma antigen (SCC-ag) analysis allows better preoperative identification of
      patients with a low likelihood for adjuvant radiotherapy than currently used
      clinical parameters. PATIENTS AND METHODS: In a cohort study, International
      Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, and
      preoperative serum SCC-ag levels, as determined by enzyme immunoassay, were
      related to the frequency of postoperative indications for adjuvant radiotherapy
      in 337 surgically treated, FIGO stage IB/IIA, squamous cell cervical cancer
      patients. RESULTS: In patients with normal preoperative SCC-ag, 16% of IB1 and
      29% of IB2/IIA had postoperative indications for adjuvant radiotherapy, in
      contrast to 57% of IB1 and 74% of IB2/IIA patients with elevated (> 1.9 ng/mL)
      serum SCC-ag (P < .001). Serum SCC-ag was the only independent predictor for a
      postoperative indication for radiotherapy (odds ratio, 7.1; P < .001).
      Furthermore, in IB1 patients that did not have indications for adjuvant
      radiotherapy, 15% of patients with elevated preoperative serum SCC-ag levels
      recurred within 2 years, compared with 1.6% of patients with normal serum SCC-ag
      levels (P = .02). CONCLUSION: In early-stage cervical cancer, determination of
      serum SCC-ag levels allows more refined preoperative estimation of the likelihood
      for adjuvant radiotherapy than current clinical parameters, and simultaneously
      identifies patients at high risk for recurrence when treated with surgery only.
      The role of preoperative serum SCC-ag in the management of patients with early
      stage cervical cancer deserves further investigation.

PMID- 15735122
TI  - Plasma bikunin as a favorable prognostic factor in ovarian cancer.
AB  - PURPOSE: Bikunin is a multifunctional glycoprotein, which mediates suppression of
      tumor cell invasion and metastasis. The measurement of bikunin levels in the
      tissue of patients with malignant diseases has been introduced as a new and
      simple diagnostic tool for the evaluation of prognosis. The high bikunin
      expression in ovarian cancer tissue would enable the use of soluble bikunin
      protein present in the circulation of ovarian cancer patients as a biomarker of
      disease. PATIENTS AND METHODS: We developed a double-antibody immunoassay for
      bikunin and detected its presence in normal human circulation. We quantified, by
      enzyme-linked immunosorbent assay and/or immunoblot assay bikunin in sera from
      200 healthy women (controls), 200 patients with benign gynecologic diseases, and
      327 patients with ovarian cancer before surgical removal of the tumor. RESULTS:
      When the values of bikunin corresponding to the median were used as the cutoff
      value (11.5 microg/mL), low plasma bikunin was strongly associated with late
      stage, suboptimal debulking with large residual tumor (> 2 cm) and low response
      to chemotherapy. The median survival time of the patients with a high bikunin
      level was more than 60 months as compared with 26 months among those with low
      bikunin level (P = .002). This difference corresponded to a 2.2-fold increased
      risk of dying for the lower plasma bikunin patients (hazard ratio, 0.45; P =
      .023) and remained significant in multivariate analysis (hazard ratio, 0.63; P =
      .041). CONCLUSION: Preoperative plasma bikunin concentration is a strong and
      independent favorable prognostic marker for ovarian cancer.

PMID- 15735123
TI  - Prognostic significance of activated Akt expression in melanoma: a
      clinicopathologic study of 292 cases.
AB  - PURPOSE: Akt is a serine/threonine kinase that leads to stimulation of cell cycle
      progression, cell proliferation, and inhibition of apoptosis. To investigate the
      role of Akt in melanoma pathogenesis, we examined the expression of phospho-Akt
      (p-Akt; Ser-473) in melanocytic lesions at different stages and analyzed the
      correlations between the p-Akt expression level and clinicopathologic factors and
      patient survival. PATIENTS AND METHODS: We evaluated the p-Akt expression in 12
      cases of normal nevi, 58 cases of dysplastic nevi, 170 cases of primary
      melanomas, and 52 cases of melanoma metastases using tissue microarray and
      immunohistochemistry. RESULTS: Strong p-Akt expression was observed in 17%, 43%,
      49%, and 77% of the biopsies in normal nevi, dysplastic nevi, primary melanoma,
      and melanoma metastases, respectively. Significant differences for p-Akt staining
      pattern were observed between normal nevi and primary melanomas (P < .05), and
      between primary melanomas and melanoma metastases (P < .001). Furthermore, our
      Kaplan-Meier survival curves showed that strong p-Akt expression is inversely
      correlated with both overall and disease-specific 5-year survival of patients
      with primary melanoma (P < .05 for both). Strikingly, our multivariate Cox
      regression analysis revealed that p-Akt is an independent prognostic factor in
      low-risk melanomas (thickness < or = 1.5 mm; relative risk, 6.44; 95% CI, 1.28 to
      32.55; P = .018). CONCLUSION: The expression of p-Akt increases dramatically with
      melanoma invasion and progression and is inversely correlated with patient
      survival. In addition, p-Akt may serve as an independent prognostic marker and
      help to identify those patients with low-risk melanomas who are at increased risk
      of death.

PMID- 15735124
TI  - TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study.
AB  - PURPOSE: Mutations of the TP53 gene have been associated with resistance to
      chemotherapy as well as poor prognosis in many different malignancies. This is
      the first prospective study of the prognostic value of somatic TP53 mutations in
      patients with newly diagnosed extremity osteosarcoma. PATIENTS AND METHODS: One
      hundred ninety-six patients with high-grade, nonmetastatic osteosarcoma of the
      extremities were enrolled from seven tertiary care institutions and observed
      prospectively for tumor recurrence (median follow-up duration, 44 months). All
      patients received neoadjuvant or adjuvant chemotherapy and surgery. Tumors were
      analyzed for the presence of TP53 mutations by polymerase chain reaction single
      strand conformation polymorphism analysis and direct DNA sequencing. The
      association of the status of the TP53 gene with the risk of systemic recurrence
      was examined using survival analyses with traditional and histologic markers as
      prognostic factors. RESULTS: Patient age was the only factor that varied with
      TP53 gene status (P = .05). No relationship was identified between TP53 status
      and systemic relapse (relative risk, 1.24; P = .41). Analyses based on missense
      or nonsense mutations gave similar results (P > .10). In multivariate analysis,
      large (> 9 cm) tumor size (relative risk, 1.9; P = .006) and poor histologic
      response (< or = 90% necrosis) to chemotherapy (relative risk, 2.14; P = .02)
      were the only significant independent predictors of systemic outcome. CONCLUSION:
      We found no evidence that TP53 mutations predict for development of metastases in
      patients with high-grade osteosarcoma. Identification of other genes that
      influence chemotherapy response and clinical outcome in osteosarcoma is needed to
      facilitate further improvements in patient outcomes.

PMID- 15735125
TI  - Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years
      of age and older with radiation therapy and high-dose alkylator-based
      chemotherapy.
AB  - PURPOSE: To describe clinical features, therapeutic approaches, and prognostic
      factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT)
      treated at St Jude Children's Research Hospital (SJCRH). PATIENTS AND METHODS:
      Primary tumor samples from patients diagnosed with ATRT at SJCRH between July
      1984 and June 2003 were identified. Pathology review included histologic,
      immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1
      (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic
      confirmation of ATRT were reviewed. RESULTS: Thirty-seven patients were diagnosed
      with ATRT at SJCRH during the 19-year study interval. Six patients were excluded
      from this clinical review based on pathologic or clinical criteria. Of the
      remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary
      lesions and metastatic disease at diagnosis were more common in younger patients
      with ATRT. All patients underwent surgical resection; 30 received subsequent
      chemotherapy. The majority of patients aged 3 years or older received
      postoperative craniospinal radiation. Two-year event-free (EFS) and overall
      survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%)
      were significantly better than those for younger patients (EFS, 11% +/- 6%; OS,
      17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics
      were predictive of survival. Three of four patients 3 years or older with
      progressive disease were successfully rescued with ifosfamide, carboplatin, and
      etoposide therapy. CONCLUSION: Children presenting with ATRT before the age of 3
      years have a dismal prognosis. ATRT presenting in older patients can be cured
      using a combination of radiation and high-dose alkylating therapy. Older patients
      with relapsed ATRT can have salvage treatment using ICE chemotherapy.

PMID- 15735127
TI  - Common polymorphism G(-248)A in the promoter region of the bax gene results in
      significantly shorter survival in patients with chronic lymphocytic Leukemia once
      treatment is initiated.
AB  - PURPOSE: Chronic lymphocytic leukemia (CLL) is characterized by the development
      of drug resistance. The underlying biologic and genetic reasons for this
      resistance are complex, but the bcl-2 gene family seems to play a critical role.
      This retrospective study assessed the clinical impact of a common single
      nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic
      lymphocytic leukemia. PATIENTS AND METHODS: The frequency of the novel
      polymorphism, G(-248)A, in the promoter region of the bax gene and bax protein
      expression was assessed in 203 CLL patients. The results were correlated with
      clinical outcome. RESULTS: The polymorphism was found in 23% of the CLL cohort
      and 15% of normal controls with no significant difference in allele frequency
      between the two groups (P = .15). It was associated with lower Bax protein
      expression and a shorter overall survival, especially in the treated patient
      group (P = .03). Furthermore, the adverse impact of the polymorphism was
      accentuated when comparing survival from the date of first treatment rather than
      diagnosis (P = .012). No significant difference in age at diagnosis, stage of
      disease at presentation, lymphocyte doubling time, time to first treatment, or
      progression-free survival were observed. CONCLUSION: The presence of this single
      nucleotide polymorphism in CLL critically influences the response to treatment
      and overall survival. Given the relatively high prevalence of this polymorphism
      in the normal population, further prospective studies in CLL and other human
      malignancies are indicated.

PMID- 15735126
TI  - Results of whole-brain radiation as salvage of methotrexate failure for
      immunocompetent patients with primary CNS lymphoma.
AB  - PURPOSE: This study evaluates the efficacy and toxicity of whole-brain radiation
      therapy (WBRT) as salvage therapy for immunocompetent patients who failed initial
      high-dose methotrexate for primary CNS lymphoma (PCNSL). PATIENTS AND METHODS:
      The study cohort included 27 consecutive patients who failed initial high-dose
      methotrexate and then received salvage WBRT (median dose, 36 Gy). Actuarial
      survival was measured from the initiation of radiotherapy. RESULTS: Ten patients
      (37%) achieved a complete radiographic response (CR), and 10 patients (37%) a
      partial response to WBRT, for a 74% overall radiographic response rate. At the
      time of maximal response, Karnofsky performance status improved in 12 (44%) of 27
      patients and at least stabilized in 67%. Median estimated survival from
      initiation of WBRT was 10.9 months (range, 0.3 to 63.7 months). The univariate
      predictor of longer survival was age less than 60 years at the time of WBRT (P =
      .028). Among patients who survived 4 months, achievement of a CR to WBRT by 4
      months (P = .002) predicted longer survival. Late treatment-associated
      neurotoxicity was diagnosed in four patients (15%) and was significantly
      associated with total radiation doses greater than 36 Gy (P = .04). No patient
      treated with daily fractions less than 1.8 Gy developed late neurotoxicity.
      CONCLUSION: For patients with PCNSL who experience treatment failure with
      methotrexate, WBRT provides high response rates (74%) and a median survival of
      10.9 months. Age less than 60 years and response to WBRT predict post-WBRT
      survival. Modest rates of late neurotoxicity (15%) were seen and were associated
      with a total dose greater than 36 Gy.

PMID- 15735128
TI  - High risk of brain metastases in surgically staged IIIA non-small-cell lung
      cancer patients treated with surgery, chemotherapy, and radiation.
AB  - PURPOSE: Lung cancer is the leading cause of cancer mortality in the United
      States. We sought to review our experience with surgically staged IIIA (N2) non
      small-cell lung cancer (NSCLC), focusing on the patterns of failure in
      consecutively treated patients from 1988 to 2000. PATIENTS AND METHODS: The
      records of 177 patients were reviewed. Collected data included stage, histology,
      use of chemotherapy and radiation, initial and subsequent sites of failure, and
      survival. One hundred twenty-four patients have died; follow-up time is 35 months
      among the remaining patients. RESULTS: The median survival from the time of
      surgery was 21.0 months, with a 3-year overall survival (OS) of 34%. Nodal
      downstaging to N0 disease correlated with OS and progression-free survival (PFS;
      P < .001). The most common site of recurrence was the brain. Thirty-four percent
      of patients recurred in the brain as their first site of failure, and 40% of
      patients developed brain metastases at some point in their course. In patients
      with nonsquamous histology and residual nodal involvement after neoadjuvant
      therapy, the risk of brain metastases was 53% at 3 years. CONCLUSION: Patients
      treated with neoadjuvant therapy for N2-positive stage IIIA NSCLC enjoy an
      advantage in both OS and PFS if their lymph node status is downstaged to N(0).
      Because brain metastases constitute the most common site of failure in these
      patients, future studies focusing on prophylaxis of brain metastases may improve
      the outcome in patients with stage IIIA NSCLC.

PMID- 15735129
TI  - Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment
      radioimmunotherapy in patients with advanced lung cancer.
AB  - PURPOSE: Tumor necrosis treatment (TNT) uses degenerating tumor cells and
      necrotic regions of tumors as targets for radioimmunotherapy. Previous studies in
      animal tumor models and clinical trials have demonstrated that when linked to the
      therapeutic radionuclide iodine-131, recombinant chimeric TNT antibody ((131)I
      chTNT) can deliver therapeutic doses to tumors regardless of the location or type
      of malignancy. Therapeutic efficacy and toxicity of (131)I-chTNT in advanced lung
      cancer patients were studied in this pivotal registration trial. PATIENTS AND
      METHODS: Patients with advanced lung cancer were treated with systemic or
      intratumoral injection of (131)I-chTNT in eight oncology centers in China. The
      objective response rate (ORR) was assessed as the primary end point. RESULTS: All
      107 patients who were entered onto the study and completed therapy had
      experienced treatment failure after prior radiotherapy or chemotherapy a mean of
      three times. The results showed an ORR of 34.6% (complete response, 3.7%; partial
      response, 30.8%; no change, 55.1%; and progressive disease, 10.3%) in all
      patients and 33% in 97 non-small-cell lung cancer patients. A biodistribution
      study demonstrated excellent localization of the radioactivity in tumors in both
      systemically and intratumorally injected patients. The most obvious adverse side
      effect was mild and reversible bone marrow suppression. CONCLUSION:
      Radioimmunotherapy with (131)I-chTNT was well tolerated and can be used
      systemically or locally to treat refractory tumors of the lung.

PMID- 15735130
TI  - Health care provider-directed intervention to increase colorectal cancer
      screening among veterans: results of a randomized controlled trial.
AB  - PURPOSE: Colorectal cancer screening is the most underused cancer screening tool
      in the United States. The purpose of this study was to test whether a health care
      provider-directed intervention increased colorectal cancer screening rates.
      PATIENTS AND METHODS: The study was a randomized controlled trial conducted at
      two clinic firms at a Veterans Affairs Medical Center. The records of 5,711
      patients were reviewed; 1,978 patients were eligible. Eligible patients were men
      aged 50 years and older who had no personal or family history of colorectal
      cancer or polyps, had not received colorectal cancer screening, and had at least
      one visit to the clinic during the study period. Health care providers in the
      intervention firm attended a workshop on colorectal cancer screening. Every 4 to
      6 months, they attended quality improvement workshops where they received group
      screening rates, individualized confidential feedback, and training on improving
      communication with patients with limited literacy skills. Medical records were
      reviewed for colorectal cancer screening recommendations and completion. Literacy
      level was assessed in a subset of patients. RESULTS: Colorectal cancer screening
      was recommended for 76.0% of patients in the intervention firm and for 69.4% of
      controls (P = .02). Screening tests were completed by 41.3% of patients in the
      intervention group versus 32.4% of controls (P = .003). Among patients with
      health literacy skills less than ninth grade, screening was completed by 55.7% of
      patients in the intervention group versus 30% of controls (P < .01). CONCLUSION:
      A provider-directed intervention with feedback on individual and firm-specific
      screening rates significantly increased both recommendations and colorectal
      cancer screening completion rates among veterans.

PMID- 15735131
TI  - Intrathecal mafosfamide: a preclinical pharmacology and phase I trial.
AB  - PURPOSE: Preclinical studies of mafosfamide, a preactivated cyclophosphamide
      analog, were performed to define a tolerable and potentially active target
      concentration for intrathecal (IT) administration. A phase I and pharmacokinetic
      study of IT mafosfamide was performed to determine a dose for subsequent phase II
      trials. PATIENTS AND METHODS: In vitro cytotoxicity studies were performed in MCF
      7, Molt-4, and rhabdomyosarcoma cell lines. Feasibility and pharmacokinetic
      studies were performed in nonhuman primates. These preclinical studies were
      followed by a phase I trial in patients with neoplastic meningitis. There were
      five dose levels ranging from 1 mg to 6.5 mg. Serial CSF samples were obtained
      for pharmacokinetic studies in a subset of patients with Ommaya reservoirs.
      RESULTS: The cytotoxic target exposure for mafosfamide was 10 micromol/L.
      Preclinical studies demonstrated that this concentration could be easily achieved
      in ventricular CSF after intraventricular dosing. In the phase I clinical trial,
      headache was the dose-limiting toxicity. Headache was ameliorated at 5 mg by
      prolonging the infusion rate to 20 minutes, but dose-limiting headache occurred
      at 6.5 mg dose with prolonged infusion. Ventricular CSF mafosfamide
      concentrations at 5 mg exceeded target cytotoxic concentrations after an
      intraventricular dose, but lumbar CSF concentrations 2 hours after the dose were
      less than 10 micromol/L. Therefore, a strategy to alternate dosing between the
      intralumbar and intraventricular routes was tested. Seven of 30 registrants who
      were assessable for response had a partial response, and six had stable disease.
      CONCLUSION: The recommended phase II dose for IT mafosfamide, administered
      without concomitant analgesia, is 5 mg over 20 minutes.

PMID- 15735132
TI  - Diagnosis and management of Waldenstrom's macroglobulinemia.
AB  - PURPOSE: To review the diagnostic criteria, prognostic factors, response
      criteria, and treatment options of patients with Waldenstrom's macroglobulinemia
      (WM). METHODS: A review of published reports was facilitated by the use of a
      MEDLINE computer search and by manual search of the Index Medicus. RESULTS: WM
      should be regarded as a distinct clinicopathologic entity and confined to those
      patients with lymphoplasmacytoid lymphoma who have demonstrable serum
      immunoglobulin M monoclonal protein. Treatment decisions should rely on specific
      clinical and laboratory criteria. Initiation of therapy should not be based on
      serum monoclonal protein levels per se. The three main choices for systemic
      primary treatment of symptomatic patients with WM include alkylating agents
      (chlorambucil), nucleoside analogs (fludarabine and cladribine), and the
      monoclonal antibody rituximab. There are no data from prospective randomized
      studies to recommend the use of one first-line agent over another, although
      consideration of a patient's candidacy for autologous stem-cell transplantation
      (ASCT) should be taken into account to avoid stem cell-damaging agents. There are
      preliminary data to suggest that combinations of nucleoside analogs and
      alkylating agents with or without rituximab may improve response rates at the
      expense of higher toxicity. CONCLUSION: WM is a distinct low-grade
      lymphoproliferative disorder. When therapy is indicated, alkylating agents,
      nucleoside analogs, and rituximab are reasonable choices. Several factors,
      including the presence of cytopenias, need for rapid disease control, candidacy
      for ASCT, age, and comorbidities, should be taken into consideration when
      choosing the most appropriate primary treatment.

PMID- 15735133
TI  - CASE 1. Complete remission to corticosteroids in an octreotide-refractory
      thymoma.

PMID- 15735134
TI  - CASE 2. Response in a patient with metastatic adrenal cortical carcinoma with
      thalidomide.

PMID- 15735135
TI  - CASE 3. Pathologic complete remission of metastatic gastrointestinal stromal
      tumor after imatinib mesylate.

PMID- 15735136
TI  - Genuine encounters: responses to death.

PMID- 15735137
TI  - Long-term survival and cure of patients diagnosed with breast cancer before age
      50 years.

PMID- 15735141
TI  - Regarding "abbreviated course of radiation therapy in older patients with
      glioblastoma multiforme: a prospective randomized clinical trial".

PMID- 15735139
TI  - Acetaminophen in cancer pain.

PMID- 15735142
TI  - Antibacterial essential oils reduce tumor smell and inflammation in cancer
      patients.

PMID- 15735144
TI  - The metrics of clinical trials.

PMID- 15735147
TI  - FDG-PET in addition to conventional work-up in non-small-cell lung cancer.

PMID- 15735148
TI  - No therapeutic effect of extended lymph node dissection for gastric cancer.

PMID- 15735152
TI  - Pathobiology of brain metastases.
AB  - Brain metastasis is a major cause of systemic cancer morbidity and mortality.
      Many factors participate in the development and maintenance of brain metastases.
      The survival of the metastasis depends upon crucial interactions between tumour
      cells and the brain microenvironment during its development at the new site. This
      review focuses on the pathobiological mechanisms involved in the establishment
      and regulation of brain metastases. Developments in molecular biology have vastly
      expanded our knowledge about the mechanisms of invasion, proliferation,
      metastatic cell signalling, and angiogenesis in brain metastases. Advances in
      this understanding of the pathobiology of brain metastasis may lead to novel
      targeted treatment paradigms and a better prognosis for patients with brain
      metastatic disease.

PMID- 15735153
TI  - Complex head and neck specimens and neck dissections. How to handle them.
AB  - Dissecting surgical specimens from the upper aerodigestive tract is often
      difficult because of their complicated anatomy. The local environment dictates
      the routes of tumour spread and surgical margins at risk, and these features
      differ for various subsites within this part of the body. The examination of
      surgical specimens of the upper aerodigestive tract should disclose whether
      postoperative adjuvant treatment is needed and allow the evaluation of
      preoperatively performed diagnostic imaging. The aim of this article is to
      provide a concise guideline for the dissection of specimens from this part of the
      body.

PMID- 15735154
TI  - Methodology for constructing guidance.
AB  - Although guidance exists for the use of many laboratory tests in a wide range of
      clinical situations, this guidance is spread among a range of literature sources,
      and is often directed at laboratory specialists rather than test users.
      Individual general practices display large variations in standardised test
      requesting, yet much of their testing activity involves a relatively small range
      of tests. This paper describes a methodological approach to review the available
      evidence and guidance and to extract relevant primary research work to examine a
      range of testing scenarios in general practice, with the aim of formulating
      guidance based on the best available evidence or consensus opinions.

PMID- 15735151
TI  - The links between axin and carcinogenesis.
AB  - The products of the two mammalian Axin genes (Axin1 and its homologue Axin2) are
      essential for the degradation of beta catenin, a component of Wnt signalling that
      is frequently dysregulated in cancer cells. Axin is a multidomain scaffold
      protein that has many functions in biological signalling pathways. Overexpression
      of mutant [corrected] axin results in axis duplication in mouse embryos. Wnt
      signalling activity determines dorsal-ventral axis formation in vertebrates,
      implicating axin as a negative regulator of this signalling pathway. In addition,
      Wnts modulate pattern formation and the morphogenesis of most organs by
      influencing and controlling cell proliferation, motility, and fate. Defects in
      different components of the Wnt signalling pathway promote tumorigenesis and
      tumour progression. Recent biochemical studies of axins indicate that these
      molecules are the primary limiting components of this pathway. This review
      explores the intriguing connections between defects in axin function and human
      diseases.

PMID- 15735155
TI  - The use of digital imaging, video conferencing, and telepathology in
      histopathology: a national survey.
AB  - AIMS: To undertake a large scale survey of histopathologists in the UK to
      determine the current infrastructure, training, and attitudes to digital
      pathology. METHODS: A postal questionnaire was sent to 500 consultant
      histopathologists randomly selected from the membership of the Royal College of
      Pathologists in the UK. RESULTS: There was a response rate of 47%. Sixty four per
      cent of respondents had a digital camera mounted on their microscope, but only
      12% had any sort of telepathology equipment. Thirty per cent used digital images
      in electronic presentations at meetings at least once a year and only 24% had
      ever used telepathology in a diagnostic situation. Fifty nine per cent had
      received no training in digital imaging. Fifty eight per cent felt that the
      medicolegal implications of duty of care were a barrier to its use. A large
      proportion of pathologists (69%) were interested in using video conferencing for
      remote attendance at multidisciplinary team meetings. CONCLUSIONS: There is a
      reasonable level of equipment and communications infrastructure among
      histopathologists in the UK but a very low level of training. There is resistance
      to the use of telepathology in the diagnostic context but enthusiasm for the use
      of video conferencing in multidisciplinary team meetings.

PMID- 15735157
TI  - Ultrarapid Ki-67 immunostaining in frozen section interpretation of gliomas.
AB  - BACKGROUND: Astrocytic tumours, the most common gliomas, are often classified
      intraoperatively using standard morphological staining. The final diagnosis and
      grading of gliomas on paraffin wax sections is often assisted by Ki-67
      immunohistochemistry, but standard immunostaining protocols take too long to be
      used intraoperatively. AIMS: To investigate a new rapid Ki-67 immunohistochemical
      test for its use in an intraoperative setting. METHODS: The new Ki-67
      immunostaining (Ultrarapid-Ki67) method on frozen sections can be carried out in
      10 minutes. Thirty four pilocytic and diffuse astrocytomas were immunostained by
      rapid Ki-67 and results were compared with corresponding MIB-1 staining,
      histological grading, and prognosis. RESULTS: The staining protocol was practical
      to perform and the results were morphologically and quantitatively
      indistinguishable from those after immunostaining with MIB-1, an antibody
      recognising Ki-67 in paraffin wax embedded tissue. A comparison of Ultrarapid
      Ki67 and MIB-1 immunostaining of paraffin wax sections showed almost identical
      quantitative correlation in astrocytic gliomas (r = 0.916; p<0.001). The
      Ultrarapid-Ki67 indices (percentage of positive cells) of low grade (I/II)
      astrocytomas ranged from 0% to 6.1%, whereas those of representative high grade
      (III/IV) tumours were significantly higher (range, 5.6-45%; p<0.001). The best
      prognostic cutoff point for Ultrarapid-Ki67 was 7.5%, which divided diffuse grade
      II-IV astrocytomas into significantly differing subsets (p = 0.0008). CONCLUSION:
      Ultrarapid-Ki67 immunostaining is a useful adjunct to morphological diagnosis and
      grading of astrocytic tumours, and as a fast test (approximately 10 minutes for
      staining plus three to four minutes for scoring), it could be used in routine
      intraoperative diagnosis of gliomas and other neoplastic diseases.

PMID- 15735158
TI  - Are routine iron stains on bone marrow trephine biopsy specimens necessary?
AB  - AIMS: To determine the role of Perls' staining in bone marrow trephine biopsy
      sections. METHODS: The haemosiderin content of 155 Perls' stained, formic acid
      decalcified trephine biopsy sections was assessed and compared with Perls'
      stained aspirate samples in 105 cases and haematoxylin and eosin (H&E) stained
      biopsy sections in all cases. RESULTS: An evaluable aspirate film with positive
      iron or at least seven negative particles was available for 105 biopsies. Only 71
      of 95 cases with detectable aspirate iron had haemosiderin detectable on a Perls'
      stained section. None of 10 samples with a negative aspirate had a positive
      trephine biopsy. Haemosiderin was positive in 101 of the 155 Perls' stained
      sections, and was detectable on the H&E stained section in 71 of these cases. In
      five of 54 cases with negative Perls' staining, a small amount of haemosiderin
      was thought to be present on H&E staining. CONCLUSIONS: Aspirate smears reflect
      bone marrow iron stores more reliably than formic acid decalcified trephine
      biopsy sections. The presence of iron in Perls' stained aspirates in 44% of cases
      with negative Perls' stained sections indicates that iron is often lost from
      sections during decalcification. However, 61% of cases with unassessable aspirate
      samples had a positive trephine biopsy Perls' stain, contributing useful clinical
      information about iron status. Preparation of Perls' stained sections only in
      cases in which aspirate samples are inadequate for iron assessment and no obvious
      haemosiderin is present in an H&E stained section could produce savings in staff
      time and reagent costs.

PMID- 15735156
TI  - CagA in Barrett's oesophagus in Colombia, a country with a high prevalence of
      gastric cancer.
AB  - BACKGROUND: In the USA, atrophic gastritis and gastric cancer are rare, whereas
      gastro-oesophageal reflux disease (GERD) is common. Infection with Helicobacter
      pylori, especially a CagA positive strain, is unusual in patients with
      GERD/Barrett's oesophagus in the USA. AIM: To examine the relation between
      Barrett's oesophagus and CagA positive H pylori in Colombia, a country with a
      high prevalence of CagA positive H pylori associated atrophic gastritis and
      gastric cancer. METHODS: Helicobacter pylori and CagA status was determined among
      Colombian patients with long segment Barrett's oesophagus and a control group
      with simple H pylori gastritis. Helicobacter pylori status was determined using a
      triple stain and CagA status was determined by immunohistochemistry using a
      specific rabbit anti-CagA serum. RESULTS: Gastric and oesophageal mucosal
      biopsies were obtained from 51 patients--39 men (mean age, 57.8 years; SD, 13.1)
      and 12 women (mean age, 51.8 years; SD, 14.4)--with documented long segment
      Barrett's oesophagus. The results were compared with 24 Colombian patients with H
      pylori gastritis without oesophageal disease. Thirty two patients with Barrett's
      oesophagus had active H pylori infection. CagA status was evaluated in a subset
      of 23 H pylori infected patients with Barrett's oesophagus, and was positive in
      eight of these patients compared with 19 of 24 controls (p = 0.01). CONCLUSIONS:
      Although most Colombian patients with Barrett's oesophagus had H pylori
      infection, CagA positive infections were unusual. These data illustrate how
      consistent corpus inflammation reduces acid secretion, which prevents Barrett's
      oesophagus among those with abnormal gastro-oesophageal reflux barriers.

PMID- 15735159
TI  - Is endomyometrial injury during termination of pregnancy or curettage following
      miscarriage the precursor to placenta accreta?
AB  - AIMS: To determine the frequency with which myometrium is removed during vacuum
      terminations of pregnancy or dilatation and curettage after miscarriage, and to
      relate these findings to subsequent placenta accreta or its proxies. METHODS:
      Archival tissues from vacuum termination of pregnancy or dilatation and blunt
      curettage after miscarriage were examined for the presence of myometrium. The
      subsequent obstetric histories were scrutinised for manual removal of placenta,
      postpartum haemorrhage, or retained placenta. A retrospective study comparing the
      frequency of miscarriage and termination in women who had or did not have a
      manual removal was also performed. RESULTS: Myometrium was seen in the products
      of conception in 44% and 35% of termination and miscarriage tissues,
      respectively. One of nine women with myometrium at miscarriage had a postpartum
      haemorrhage in a subsequent pregnancy whereas, of the 21 women without myometrium
      at miscarriage, three required manual removal and seven had a postpartum
      haemorrhage afterwards. A past history of termination and/or miscarriage was more
      frequent in multigravid women who had a manual removal than those who did not.
      CONCLUSIONS: Endomyometrial injury is frequent at termination or dilatation and
      curettage after miscarriage, but the relation to subsequent placenta accreta
      remains unclear. Women requiring a manual removal of the placenta were likely to
      have had a past history of termination and/or miscarriage.

PMID- 15735161
TI  - Aberrations in the mismatch repair genes and the clinical impact on oesophageal
      squamous carcinomas from a high incidence area in South Africa.
AB  - AIMS: To investigate the incidence of genetic aberrations in the DNA repair genes
      in a cohort of oesophageal cancers. METHODS: One hundred oesophagectomy samples
      of squamous cell carcinoma were studied. Normal and tumour DNA were isolated
      using a standard phenol/chloroform extraction procedure. Six recommended
      microsatellite loci with high informativity were analysed. The following markers
      were used: D2S123 (2p), D3S659 (3p), D3S1255 (3p), Bat 25 (4q), Bat 26 (2p), and
      Bat 40 (1p). The results were analysed using software attached to an automated
      DNA sequencer. The molecular data were then correlated with clinicopathological
      parameters. RESULTS: The incidence of microsatellite instability and loss of
      heterozygosity was very low. There was no significant correlation between the
      clinicopathological and molecular data. However, D2S123 genetic abnormalities
      were seen more frequently in both moderately and well differentiated tumours than
      in poorly differentiated tumours (p = 0.033). Follow up data were available for
      only 67 of the 100 patients. Fifty patients were alive and 17 patients had died.
      CONCLUSION: Low frequencies of genetic aberrations in these mismatch repair loci
      are found in squamous carcinomas of the oesophagus from a high incidence area in
      South Africa.

PMID- 15735160
TI  - Development of a quantitative assay for SARS coronavirus and correlation of GAPDH
      mRNA with SARS coronavirus in clinical specimens.
AB  - AIMS: To develop a quantitative reverse transcriptase polymerase chain reaction
      (Q-RT-PCR) for severe acute respiratory syndrome coronavirus (SARS-CoV) detection
      and explore the potential of using glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) mRNA as an internal control to exclude false negative results. METHODS:
      SARS-CoV and GAPDH mRNA were both measured in 26 specimens from 16 patients with
      SARS, 40 follow up specimens from the same batch of patients, and appropriate
      control subjects. The relation between SARS positivity and GAPDH mRNA
      concentration was investigated using the chi2 test. Increasing the sensitivity
      for SARS-CoV and GAPDH mRNA detection was investigated in follow up specimens in
      which SARS-CoV and GAPDH mRNA were not detected initially. RESULTS: Varying
      amounts of SARS-CoV were found in the 26 SARS-CoV positive specimens and SARS-CoV
      was not detected in the 40 follow up specimens and controls. In addition,
      concentrations of GAPDH mRNA were significantly different between the patients
      with SARS, follow up specimens, and healthy controls (Kruskal-Wallis test,
      p<0.05). Moreover, GAPDH mRNA concentrations were highly correlated with SARS-CoV
      positivity (chi2 = 5.43; p<0.05). Finally, SARS-CoV and GAPDH mRNA were both
      detected in three follow up urine specimens that were initially negative when the
      amount of cDNA used was increased from 5 microl to 10 and 15 microl. CONCLUSIONS:
      This Q-RT-PCR assay can be used to detect SARS-CoV. Moreover, GAPDH mRNA may be
      useful to rule out false negative results in SARS-CoV detection, and the current
      extraction method for urine may not be sensitive enough to detect low titres of
      SARS-CoV.

PMID- 15735162
TI  - Mast cell distribution in normal adult skin.
AB  - AIMS: To investigate mast cell distribution in normal adult skin to provide a
      reference range for comparison with mastocytosis. METHODS: Mast cells (MCs) were
      counted in uninvolved skin adjacent to basal cell carcinomas and other
      dermatological disorders in adults. RESULTS: There was an uneven distribution of
      MCs in different body sites using the anti-tryptase monoclonal antibody
      technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar,
      but were significantly different from those found on the lower leg and forearm.
      Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at
      proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent
      diagnosis and age, this difference was consistent. The numbers of MCs in
      uninvolved skin adjacent to basal cell carcinomas and other dermatological
      disorders were not different from those in the control group. Differences in the
      numbers of MCs between the distal and the proximal body sites must be considered
      when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in
      patients with mastocytosis underlined the variation in the numbers of MCs in
      mastocytosis and normal skin, but showed a considerable overlap. The observed
      numbers of MCs in adults cannot be extrapolated to children. CONCLUSIONS: MC
      numbers varied significantly between proximal and distal body sites and these
      differences must be considered when MCs are counted for a reliable diagnosis of
      mastocytosis. There was a considerable overlap between the numbers of MCs in
      mastocytosis and normal skin.

PMID- 15735163
TI  - Basal cell hyperplasia and basal cell carcinoma of the prostate: a comprehensive
      review and discussion of a case with c-erbB-2 expression.
AB  - Prostatic basal cell proliferations range from ordinary basal cell hyperplasia
      (BCH) to florid basal cell hyperplasia to basal cell carcinoma. The distinction
      between these forms of BCH, including the variant with prominent nucleoli
      (formerly called atypical BCH), and basal cell carcinoma depends on morphological
      and immunohistochemical criteria and, in particular, on the degree of cell
      proliferation. In florid BCH, the proliferation index is intermediate between
      ordinary BCH and basal cell carcinoma. Immunohistochemistry is also useful for
      identifying the cell composition of the basal cell proliferations, including the
      basal cell nature of the cells, their myoepithelial differentiation, and c-erbB-2
      oncoprotein expression. Based on the information derived from the literature and
      on the appearance and follow up of the case presented here, florid BCH might
      represent a lesion with an intermediate position between ordinary BCH and basal
      cell carcinoma. However, criteria useful for the identification of those cases
      with a true precursor nature are not available. In general, basal cell carcinoma
      is seen as a low grade carcinoma. The immunohistochemical expression of the c
      erbB-2 oncoprotein, similar to that seen in breast cancer, might have therapeutic
      importance.

PMID- 15735164
TI  - Tenascin-C in primary Merkel cell carcinoma.
AB  - BACKGROUND/AIMS: Merkel cell carcinoma (MCC) is a rare malignant cutaneous
      neuroendocrine tumour that mostly affects the elderly. It shows rapid progression
      of the primary tumour, together with a vertical growth pattern into the
      underlying subcutaneous tissue. Metastatic dissemination to regional lymph nodes
      is early and frequent. Tenascin-C (Tn-C) is a large extracellular matrix
      glycoprotein that is expressed in various benign and malignant processes.
      Expression of Tn-C is also associated with invasion and cellular proliferation,
      and is often downregulated in fully evolved advanced carcinomas. In previous
      studies, Tn-C expression correlated with prognosis in tumours of different
      origin. METHODS: Immunohistochemistry was used to investigate the expression of
      Tn-C in 25 MCC specimens and to evaluate the prognostic importance of this
      glycoprotein. RESULTS: Seventeen samples expressed Tn-C. Staining was mainly seen
      in the invasion borders and within the connective tissue septae inside the
      tumours. The expression of Tn-C correlated significantly with large tumour size.
      There was also frequent expression of Tn-C in primary tumours with metastatic
      dissemination. Most of the Tn-C negative samples were of small size. CONCLUSIONS:
      Tn-C expression seems to increase with tumour size and malignant behaviour.
      Expression was slightly enhanced in tumours with high proliferative indices.
      Expression is seen mainly in areas of invasive growth and, in this respect,
      resembles that of other invasive tumours.

PMID- 15735165
TI  - Clostridium bacteraemia characterised by 16S ribosomal RNA gene sequencing.
AB  - BACKGROUND: Owing to problems in accurate species identification of the diverse
      genus clostridium, the epidemiology and pathogenicity of many species are not
      fully understood. Moreover, previous studies on clostridium bacteraemia have been
      limited and relied only on phenotypic species identification. AIMS: To
      characterise the epidemiology, disease spectrum, and outcome of clostridium
      bacteraemia using 16S ribosomal RNA (rRNA) gene sequencing. METHOD: During a four
      year period (1998-2001), all cases of clostridium bacteraemia were prospectively
      studied and all "non-perfringens" clostridium isolates identified to the species
      level by 16S rRNA gene sequencing. RESULTS: Fifty one blood culture isolates were
      identified as Clostridium perfringens and 17 belonged to 11 other clostridium
      species. The first case of C disporicum infection and two cases of clostridium
      bacteraemia in children with intussusception were also described. Of the 68
      clostridium isolates from 68 different patients, 38 were associated with
      clinically relevant bacteraemia. The gastrointestinal and hepatobiliary tracts
      were common sites of both underlying disease and portal of entry in these
      patients. Clostridium perfringens accounted for 79% of all clinically relevant
      bacteraemia, with the remainder caused by a diversity of species. The
      attributable mortality rate of clinically relevant clostridium bacteraemia was
      29%. Younger age and underlying gastrointestinal/hepatobiliary tract disease were
      associated with mortality (p < 0.05). CONCLUSIONS: Patients with clinically
      relevant clostridium bacteraemia should be investigated for the presence of
      underlying disease processes in the gastrointestinal or hepatobiliary tracts. 16S
      rRNA gene analysis will continue to be useful in further understanding the
      pathogenicity of various clostridium species.

PMID- 15735166
TI  - The role of CA125 in clinical practice.
AB  - BACKGROUND: CA125 is a high molecular weight glycoprotein, which is expressed by
      a large proportion of epithelial ovarian cancers. The sensitivity and specificity
      of CA125 are poor and there are no guidelines produced by the Royal College of
      Pathologists or the Association of Clinical Biochemists to aid clinicians and
      laboratories in its most appropriate use. AIM: To identify the patient population
      having a CA125 measurement and to determine its contribution to individual
      patient management. METHODS: A retrospective case note audit looking at patients
      who had a CA125 measurement performed between April 2000 and April 2002. RESULTS:
      The study comprised 799 patients; 751 (94%) were female and 48 (6%) male; 221
      (29%) females and 22 (46%) males had an abnormal result. CA125 was mainly used to
      investigate a wide range of signs and symptoms, and few tests were for follow up
      or screening of ovarian cancer. In female patients having a CA125 for suspicion
      of malignancy/ovarian cancer, only 39 (20%) of the abnormal results were caused
      by ovarian cancer. False positive results were largely caused by another
      malignancy (48 cases; 26%), benign ovarian disease (26 cases; 14%), and benign
      gynaecological conditions, particularly leiomyomas (18 cases; 9%). The
      specificity of CA125 for ovarian cancer increased with concentrations >1000
      kU/litre. CONCLUSIONS: These results confirm the high false positive rate and
      poor sensitivity and specificity associated with CA125. The substantial
      inappropriate usage of CA125 has led to results that are useless to the
      clinician, have cost implications, and add to patient anxiety and clinical
      uncertainty.

PMID- 15735167
TI  - DNA and RNA obtained from Bouin's fixed tissues.
AB  - BACKGROUND: The use in many countries of acid fixatives, such as Bouin's
      solution, has limited the use of archival tissue for molecular analysis. An
      acidic environment is one of the main causes of DNA degradation. Moreover, RNA
      extraction is difficult in these types of fixed tissues. AIMS: To amplify DNA and
      RNA from Bouin's fixed tissues. METHODS: DNA and RNA were extracted from 20
      breast cancer samples that had been routinely fixed in Bouin's fixative.
      Amplification of several genes using primers that produced amplicons of different
      lengths was carried out using the polymerase chain reaction (PCR) for DNA (with
      and without restoration) and reverse transcription PCR for RNA. RESULTS: The acid
      environment of Bouin's fixative damaged both DNA and RNA. However, amplification
      was successful when the amplicon length was reduced to about 80 bp for RNA and
      100-200 bp for DNA, especially if submitted to DNA reconstruction procedures.
      CONCLUSIONS: It is possible to recover and analyse DNA and RNA from Bouin's fixed
      and paraffin wax embedded tissues.

PMID- 15735168
TI  - An Ashkenazi Jewish woman presenting with favism.
AB  - The case of a 44 year old Ashkenazi Jewish woman of Russian origin who presented
      with a typical clinical and haematological picture of favism is reported. There
      was initial difficulty in confirming glucose-6-phosphate dehydrogenase (G6PD)
      deficiency because the enzyme concentrations were normal at presentation, but
      later fell to a concentration compatible with heterozygosity for the
      Mediterranean type of G6PD deficiency. The diagnosis was also later confirmed by
      gene analysis. The reasons for the difficulties in the initial confirmation of
      the diagnosis and the normal G6PD enzyme activity at presentation are discussed.

PMID- 15735169
TI  - Myelodysplastic syndrome with erythroid hypoplasia.
AB  - The incidence of myelodysplastic syndrome (MDS) with erythroid hypoplasia/aplasia
      is probably underestimated because in most patients it is mistaken for acquired
      pure red blood cell aplasia. This report describes three children who fulfilled
      the criteria for MDS with erythroid hypoplasia/aplasia. All these patients had
      transfusion dependent anaemia, reticulocytopenia, erythroid hypoplasia/aplasia,
      severe dysgranulopoiesis, and dysmegakaryopoiesis.

PMID- 15735171
TI  - Massive myeloid sarcoma affecting the central nervous system, mediastinum,
      retroperitoneum, liver, and rectum associated with acute myeloblastic leukaemia:
      a case report.
AB  - Myeloid sarcomas are extramedullary tumours with granulocytic precursors. When
      associated with acute myelogenous leukaemia (AML), these tumours usually affect
      no more than two different extramedullary regions. This report describes a
      myeloid sarcoma associated with AML with tumour formation at five anatomical
      sites. The patient was a 37 year old man admitted in September 1999 with a two
      month history of weight loss, symptoms of anaemia, rectal bleeding, and left
      facial nerve palsy. The anatomical sites affected were: the rectum, the right
      lobe of the liver, the mediastinum, the retroperitoneum, and the central nervous
      system. A bone marrow smear was compatible with AML M2. Flow cytometry showed
      that the peripheral blood was positive for CD4, CD11, CD13, CD14, CD33, CD45, and
      HLA-DR. A karyotypic study of the bone marrow revealed an 8;21 translocation. The
      presence of multiple solid tumours in AML is a rare event. Enhanced expression of
      cell adhesion molecules may be the reason why some patients develop myeloid
      sarcomas.

PMID- 15735170
TI  - Immunohistochemical assays in prostatic biopsies processed in Bouin's fixative.
AB  - AIMS: To investigate the problems involved in undertaking immunohistochemistry
      (IHC) and nuclear morphometry using Bouin's fixed prostate biopsies. METHODS:
      Archival Bouin's fixed and formalin fixed, paraffin wax embedded prostatic
      biopsies were immunostained for three nuclear biomarkers (minichromosome
      maintenance protein 2 (MCM-2), p27, and Ki-67), one membrane localised biomarker
      (C-erb-B2), CD34, and alpha methylacyl-CoA racemase (AMACR). The quality of IHC
      staining was compared between tissues prepared separately in both fixatives.
      Feulgen staining was also performed on Bouin's fixed tissues to check its
      suitability for nuclear morphometry. RESULTS: MCM-2 staining was completely
      negative in Bouin's fixed tissues, whereas p27 showed more background and excess
      cytoplasmic staining in Bouin's fixed versus formalin fixed tissues. C-erb-B2
      showed non-specific, strong luminal cell staining in the Bouin's fixed tissue.
      Feulgen staining was also very weak in Bouin's fixed tissue. However, Ki-67,
      AMACR, and CD34 worked equally well in Bouin's and formalin fixed tissues.
      CONCLUSIONS: Bouin's fixed tissues may be unsuitable when subsequent IHC and
      morphometry are contemplated. An awareness of which antibodies are suitable for
      use in Bouin's fixed biopsies is essential.

PMID- 15735172
TI  - An immunohistochemical analysis to evaluate an inverse correlation between
      Runx2/Cbfa1 and NF kappa B in human osteosarcoma.
AB  - BACKGROUND: Dominant negative inhibition of nuclear factor kappa B (NF kappa B)
      signalling activity in a human osteosarcoma cell line (Saos2) results in
      malignant reversion and the induction of the osteoblast differentiating
      transcription factor, Runx2/Cbfa1. This observation suggests that there is an
      inverse relation between a transcription factor associated with malignant
      progression and chemoresistance (NF kappa B) and an osteoblast differentiating
      transcription factor (Runx2/Cbfa1). AIMS: To assess and correlate Runx2/Cbfa1 and
      NF kappa B (p65) immunoreactivity in human osteosarcoma. METHODS: Runx2/Cbfa1 and
      NFkappaB (p65) immunoreactivity was assessed on 11 paraffin wax embedded archival
      specimens of human primary osteosarcoma by standard immunohistochemical methods
      and scored on a scale of 0-3. A Pearson correlation analysis between Runx2/Cbfa1
      and NF kappa B (p65) scores was established. RESULTS: Runx2/Cbfa1 was expressed
      constitutively in all pathology specimens of human osteosarcoma. Of note, a
      chondroblastic osteosarcoma showed the highest Runx2/Cbfa1 immunoreactivity. A
      Pearson correlation did not support an inverse correlation between Runx2/Cbfa1
      and NF kappa B (p65) scores (r = 0.57) in human osteosarcoma. CONCLUSION:
      Runx2/Cbfa1 immunoreactivity does not inversely correlate with NF kappa B
      immunoreactivity, and thus cannot serve as an indirect measure of NF kappa B
      activity or an independent predictive or prognostic indicator.

PMID- 15735174
TI  - Osseous metaplasia in a benign ovarian cyst in association with cloacal anomaly.

PMID- 15735173
TI  - Initial diagnosis of small lymphocytic lymphoma in parotidectomy for Warthin
      tumour, a rare collision tumour.
AB  - Warthin tumours (WT) and malignant lymphomas are only rarely associated, and most
      are examples of involvement of the lymphoid stroma of WT by a disseminated
      lymphoma. This report describes a case where excision of a parotid mass led to
      the initial diagnosis of WT and small lymphocytic lymphoma (SLL). The diagnosis
      of SLL was confirmed by immunohistochemistry and molecular studies. The patient
      had stage IV A disease and is currently in chemotherapy induced complete
      remission. This case highlights the extremely rare association of SLL with WT and
      the importance of evaluation of the WT stroma, where the pale proliferation
      centres of SLL may mimic germinal centres of reactive lymphoid nodules.

PMID- 15735175
TI  - Molecular confirmation of invasive infection caused by Chaetomium globosum.

PMID- 15735176
TI  - Expression of HIF-1alpha in human tumours.

PMID- 15735177
TI  - VEGF-D and HIF-1alpha in breast cancer.

PMID- 15735178
TI  - Congenital bronchogenic cyst in the gastric mucosa.

PMID- 15735179
TI  - The case for biennial retinopathy screening in children and adolescents.
AB  - OBJECTIVE: Current guidelines recommend annual retinopathy screening 2 years
      after onset (for pubertal-onset type 1 diabetes) and after 5 years (or age 11,
      whichever is earlier) for prepubertal onset. Our aim was to describe the natural
      history of retinopathy and to explore optimal retinal screening intervals for
      children and adolescents (aged <20 years) screened according to these guidelines.
      RESEARCH DESIGN AND METHODS: More than 1,000 children and adolescents, followed
      longitudinally, were screened for retinopathy using seven-field stereoscopic
      fundus photography through dilated pupils. Of these, 668 had baseline and follow
      up retinal screening. Using generalized estimating equations, we compared the
      risk of retinopathy with baselines at yearly intervals, in older and younger
      groups, in higher risk groups (diabetes duration >10 years or HbA(1c) >10% at any
      screening), and after stratification </=10 and <10 years in duration. RESULTS:
      After 1 year, retinopathy did not increase significantly in the older group (n =
      618, median HbA(1c) 8.7%, range 8.0-9.5), younger group (n = 50, median HbA(1c)
      8.5%, range 8.0-9.2), or the higher-risk groups. Retinopathy increased
      significantly after 2 years in the older group (P = 0.003) but not until 6 years
      in the younger group (P = 0.01). In the group with HbA(1c) >10% recorded at any
      visit, retinopathy increased significantly after 2 years (P = 0.001) but not
      until 3 years in the group whose HbA(1c) was always </=10% (P = 0.003). After the
      second eye assessment, retinopathy did not increase significantly until 3 and 6
      years later in the older and younger groups, respectively (P = 0.028 and 0.014).
      CONCLUSIONS: These results suggest that adolescents (in reasonable metabolic
      control) could safely be screened every 2 years rather than the currently
      recommended 1-year interval. In younger children, the next screening interval
      could be >2 years later. Individuals with especially poor control, duration >10
      years, or significant retinopathy should be screened more frequently.

PMID- 15735180
TI  - Sex disparities in treatment of cardiac risk factors in patients with type 2
      diabetes.
AB  - OBJECTIVE: Diabetes eliminates the protective effect of female sex on the risk of
      coronary heart disease (CHD). We assessed sex differences in the treatment of CHD
      risk factors among patients with diabetes. RESEARCH DESIGN AND METHODS: A cross
      sectional analysis included 3,849 patients with diabetes treated in five academic
      internal medicine practices from 2000 to 2003. Outcomes were stratified by the
      presence of CHD and included adjusted odds ratios (AORs) that women (relative to
      men) were treated with hypoglycemic, antihypertensive, lipid-lowering medications
      or aspirin (if indicated) and AORs of reaching target HbA(1c), blood pressure, or
      lipid levels. RESULTS: Women were less likely than men to have HbA(1c) <7%
      (without CHD: AOR 0.84 [95% CI 0.75-0.95], P = 0.005; with CHD: 0.63 [0.53-0.75],
      P < 0.0001). Women without CHD were less likely than men to be treated with lipid
      lowering medication (0.82 [0.71-0.96], P = 0.01) or, when treated, to have LDL
      cholesterol levels <100 mg/dl (0.75 [0.62-0.93], P = 0.004) and were less likely
      than men to be prescribed aspirin (0.63 [0.55-0.72], P < 0.0001). Women with
      diabetes and CHD were less likely than men to be prescribed aspirin (0.70 [0.60
      0.83], P < 0.0001) or, when treated for hypertension or hyperlipidemia, were less
      likely to have blood pressure levels <130/80 mmHg (0.75 [0.69-0.82], P < 0.0001)
      or LDL cholesterol levels <100 mg/dl (0.80 [0.68-0.94], P = 0.006). CONCLUSIONS:
      Women with diabetes received less treatment for many modifiable CHD risk factors
      than diabetic men. More aggressive treatment of CHD risk factors in this
      population offers a specific target for improvement in diabetes care.

PMID- 15735181
TI  - Has control of hypercholesterolemia and hypertension in type 1 diabetes improved
      over time?
AB  - OBJECTIVE: To determine the extent to which patients' awareness, treatment, and
      control of hypertension and hypercholesterolemia have changed over time and to
      examine factors associated with awareness and treatment in a type 1 diabetes
      population. RESEARCH DESIGN AND METHODS: Data from six examinations conducted
      over 10 years from the Pittsburgh Epidemiology of Diabetes Complications Study, a
      prospective study of subjects with childhood-onset (<17 years of age) type 1
      diabetes diagnosed between 1950 and 1980 and followed since 1986, were analyzed.
      Hypertension and hypercholesterolemia were defined according to the concurrent
      Joint National Committee and National Cholesterol Education Program Adult
      Treatment Panel criteria, respectively. RESULTS: Results demonstrated that
      awareness of both conditions has improved; however, control is not optimal (e.g.,
      only 32.1 and 28% of those with hypertension in 1986-1988 and 1996-1998 were
      controlled, while for hypercholesterolemia, the rates were 0 and 5.5%,
      respectively). Stratified by age-group (18-29, 30-39, and >40 years), the
      youngest subjects with hypercholesterolemia were least likely to be treated and
      controlled to goal levels. Older age and physician contact were correlates of
      awareness and treatment of hypertension at baseline, while presence of renal or
      coronary complications was also associated with awareness and treatment of both
      hypertension and hypercholesterolemia at the 10-year follow-up. CONCLUSIONS:
      There is a considerable treatment gap, particularly for hypercholesterolemia.
      Improved treatment of both hypertension and hypercholesterolemia are clearly
      needed, particularly hypercholesterolemia in younger age-groups who have not yet
      experienced long-term complications.

PMID- 15735182
TI  - Dosage effects of diabetes self-management education for Mexican Americans: the
      Starr County Border Health Initiative.
AB  - OBJECTIVE: The objective of this study was to compare two diabetes self
      management interventions designed for Mexican Americans: "extended" (24 h of
      education, 28 h of support groups) and "compressed" (16 h of education, 6 h of
      support groups). Both interventions were culturally competent regarding language,
      diet, social emphasis, family participation, and incorporating cultural beliefs.
      RESEARCH DESIGN AND METHODS: We recruited 216 persons between 35 and 70 years of
      age diagnosed with type 2 diabetes >/=1 year. Intervention groups of eight
      participants and eight support persons were randomly assigned to the compressed
      or extended conditions. The interventions differed in total number of contact
      hours over the year-long intervention period, with the major difference being the
      number of support group sessions held. The same information provided in the
      educational sessions of the extended intervention was compressed into fewer
      sessions, thus providing more information during each group meeting. RESULTS: The
      interventions were not statistically different in reducing HbA(1c); however, both
      were effective. A "dosage effect" of attendance was detected with the largest
      HbA(1c) reductions achieved by those who attended more of the extended
      intervention. For individuals who attended >/=50% of the intervention, baseline
      to 12-month HbA(1c) change was -0.6 percentage points for the compressed group
      and -1.7 percentage points for the extended group. CONCLUSIONS: Both culturally
      competent diabetes self-management education interventions were effective in
      promoting improved metabolic control and diabetes knowledge. A dosage effect was
      evident; attending more sessions resulted in greater improvements in metabolic
      control.

PMID- 15735183
TI  - Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple
      daily injection of insulin aspart/insulin glargine in type 1 diabetic patients
      previously treated with CSII.
AB  - OBJECTIVE: Multiple daily injection (MDI) therapy of bolus insulin aspart and
      basal insulin glargine was compared with continuous subcutaneous insulin infusion
      (CSII) with aspart in type 1 diabetic patients previously treated with CSII.
      RESEARCH DESIGN AND METHODS: One hundred patients were enrolled in a randomized,
      multicenter, open-label, crossover study. After a 1-week run-in period with
      aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart
      immediately before each meal and glargine at bedtime) and 50 subjects continued
      CSII. After 5 weeks of the first treatment, subjects crossed over to the
      alternate treatment for 5 weeks. During the last week of each treatment period,
      subjects wore a continuous glucose monitoring system for 48-72 h. RESULTS: Mean
      serum fructosamine levels were significantly lower after CSII therapy than after
      MDI therapy (343 +/- 47 vs. 355 +/- 50 micromol/l, respectively; P = 0.0001).
      Continuous glucose monitoring profiles over a 24-h time period showed that
      glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under
      the curve (AUC) glucose >/=80 mg/dl (1,270 +/- 742 vs. 1,664 +/- 1,039 mg . h .
      dl(-1); P < 0.001) and AUC glucose >/=140 mg/dl (464 +/- 452 vs. 777 +/- 746 mg .
      h . dl(-1), CSII vs. MDI, respectively; P < 0.001). Similar percentages of
      subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal
      (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major
      hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes).
      CONCLUSIONS: In a trial of short duration, CSII therapy with insulin aspart
      resulted in lower glycemic exposure without increased risk of hypoglycemia, as
      compared with MDI with insulin aspart and glargine.

PMID- 15735184
TI  - Comparative outcomes study of metformin intervention versus conventional approach
      the COSMIC Approach Study.
AB  - OBJECTIVE: Metformin was approved by the Food and Drug Administration in 1995
      subject to the conduct of a randomized trial to evaluate the risk of lactic
      acidosis or other serious adverse events (SAEs) with this agent, under usual care
      conditions. RESEARCH DESIGN AND METHODS: The Comparative Outcomes Study of
      Metformin Intervention versus Conventional (COSMIC) Approach Study was a
      randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2
      diabetic patients suboptimally controlled on diet or sulfonylurea. Patients
      received metformin (n = 7,227) or other usual care treatments (n = 1,505). The
      primary end point was the incidence of SAEs, death, and hospitalization. RESULTS:
      SAEs occurred in 10.3% (95% CI 9.6-11.1%) of the metformin group and in 11.0%
      (9.5-12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur.
      All-cause mortality (1.1% [0.9-1.4%] vs. 1.3% [0.8-2.0%], P = 0.596) and
      hospitalization (9.4% [8.8-10.1%] vs. 10.4% [8.9-12.1%], P = 0.229) were similar
      between groups. CONCLUSIONS: The incidence of SAEs was similar between groups.
      Lactic acidosis was not observed. Metformin may be safely prescribed for type 2
      diabetes if contraindications and warnings are respected. This study demonstrates
      the utility of large, simple trials for risk evaluation of treatments for common
      diseases.

PMID- 15735185
TI  - Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2
      years in patients with type 2 diabetes.
AB  - OBJECTIVE: The hypothesis that pioglitazone treatment is superior to gliclazide
      treatment in sustaining glycemic control for up to 2 years in patients with type
      2 diabetes was tested. RESEARCH DESIGN AND METHODS: This was a randomized,
      multicenter, double-blind, double-dummy, parallel-group, 2-year study.
      Approximately 600 patients from 98 centers participated. Eligible patients had
      completed a previous 12-month study and consented to continue treatment for a
      further year. To avoid selection bias, all patients from all centers were
      included in the primary analysis (a comparison of the time-to-failure
      distributions of the two groups by using a log-rank test) regardless of whether
      they continued treatment for a 2nd year. By using repeated-measures ANOVA, time
      course of least square means of HbA(1c) and homeostasis model of assessment
      (HOMA) indexes (HOMA-%S and HOMA-%B) were analyzed. RESULTS: A greater proportion
      of patients treated with pioglitazone maintained HbA(1c) <8% over the 2-year
      period than those treated with gliclazide. A difference between the Kaplan-Meier
      curves was apparent as early as week 32 and widened at each time point
      thereafter, becoming statistically significant from week 52 onward. At week 104,
      129 (47.8%) of 270 pioglitazone-treated patients and 110 (37.0%) of 297
      gliclazide-treated patients maintained HbA(1c) <8%. Compared with gliclazide
      treatment, pioglitazone treatment produced a larger decrease in HbA(1c), a larger
      increase in HOMA-%S, and a smaller increase in HOMA-%B during the 2nd year of
      treatment. CONCLUSIONS: Pioglitazone is superior to gliclazide in sustaining
      glycemic control in patients with type 2 diabetes during the 2nd year of
      treatment.

PMID- 15735186
TI  - Evaluation of removable and irremovable cast walkers in the healing of diabetic
      foot wounds: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a
      removable cast walker (RCW) and an "instant" total contact cast (iTCC) in healing
      neuropathic diabetic foot ulcerations. RESEARCH DESIGN AND METHODS: We randomly
      assigned 50 patients with University of Texas grade 1A diabetic foot ulcerations
      into one of two off-loading treatment groups: an RCW or the same RCW wrapped with
      a cohesive bandage (iTCC) so patients could not easily remove the device.
      Subjects were evaluated weekly for 12 weeks or until wound healing. RESULTS: An
      intent-to-treat analysis showed that a higher proportion of patients had ulcers
      that were healed at 12 weeks in the iTCC group than in the RCW group (82.6 vs.
      51.9%, P = 0.02, odds ratio 1.8 [95% CI 1.1-2.9]). Of the patients with ulcers
      that healed, those treated with an iTCC healed significantly sooner (41.6 +/-
      18.7 vs. 58.0 +/- 15.2 days, P = 0.02). CONCLUSIONS: Modification of a standard
      RCW to increase patient adherence to pressure off-loading may increase both the
      proportion of ulcers that heal and the rate of healing of diabetic neuropathic
      wounds.

PMID- 15735187
TI  - A randomized trial of two irremovable off-loading devices in the management of
      plantar neuropathic diabetic foot ulcers.
AB  - OBJECTIVE: The purpose of this study was to compare the effectiveness of a
      removable cast walker (RCW) rendered irremovable (iTCC) with the total contact
      cast (TCC) in the treatment of diabetic neuropathic plantar foot ulcers. RESEARCH
      DESIGN AND METHODS: In a prospective, randomized, controlled trial, 41
      consecutive diabetic patients with chronic, nonischemic, neuropathic plantar foot
      ulcers were randomly assigned to one of two groups: a RCW rendered irremovable by
      wrapping it with a single layer of fiberglass casting material (i.e., an iTCC) or
      a standard TCC. Primary outcome measures were the proportion of patients with
      ulcers that healed at </=12 weeks, healing rates, complication rates, cast
      placement/removal times, and costs. RESULTS: The proportions of patients with
      ulcers that healed within 12 weeks in the iTCC and TCC groups were 80 and 74%,
      respectively (94 and 93%, respectively, when patients who were lost to follow-up
      were excluded). Survival analysis (healing rates) was statistically equivalent in
      the two groups, as were complication rates, but with a trend toward benefit in
      the iTCC group. The iTCC took significantly less time to place and remove than
      the TCC with 39% and 36% reductions, respectively. There was also an overall
      lower cost associated with the use of the iTCC compared with the TCC.
      CONCLUSIONS: The iTCC may be equally efficacious, faster to place, easier to use,
      and less expensive than the TCC in the treatment of diabetic plantar neuropathic
      foot ulcers.

PMID- 15735188
TI  - Effects of exercise on the absorption of insulin glargine in patients with type 1
      diabetes.
AB  - OBJECTIVE: To study the effects of exercise on the absorption of the basal long
      acting insulin analog insulin glargine (Lantus), administered subcutaneously in
      individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 13
      patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen
      were studied. (125)I-labeled insulin glargine at the usual basal insulin dose was
      injected subcutaneously into the thigh on the evening (2100) before the study day
      on two occasions 1 week apart. Patients were randomly assigned to 30 min intense
      exercise (65% peak oxygen uptake [Vo(2peak)]) on one of these visits. The decay
      of radioactive insulin glargine was compared on the two occasions using a
      thallium-activated Nal gamma counter. Blood samples were collected at regular
      intervals on the study days to assess plasma glucose and insulin profiles.
      RESULTS: No significant difference was found in the (125)I-labeled insulin
      glargine decay rate on the two occasions (exercise vs. no exercise; repeated
      measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was
      observed over the exercise period (area under curve above fasting [DeltaAUC]
      glucose: -0.39 +/- 0.11 vs. -1.30 +/- 0.16 mmol . l(-1) . h(-1); nonexercise vs.
      exercise; P = 0.001), but insulin levels did not differ significantly on the two
      occasions (DeltaAUC insulin: -2.1 +/- 3.9 vs. 1.5 +/- 6.2 pmol . l(-1) . h(-1);
      nonexercise versus exercise; P = 0.507). CONCLUSIONS: An intense 30-min period of
      exercise does not increase the absorption rate of the subcutaneously injected
      basal long-acting insulin analog insulin glargine in patients with type 1
      diabetes.

PMID- 15735189
TI  - Caffeine ingestion is associated with reductions in glucose uptake independent of
      obesity and type 2 diabetes before and after exercise training.
AB  - OBJECTIVE: We investigated the effect of caffeine ingestion on insulin
      sensitivity in sedentary lean men (n = 8) and obese men with (n = 7) and without
      (n = 8) type 2 diabetes. We also examined whether chronic exercise influences the
      relationship between caffeine and insulin sensitivity in these individuals.
      RESEARCH DESIGN AND METHODS: Subjects underwent two hyperinsulinemic-euglycemic
      clamp procedures, caffeine (5 mg/kg body wt) and placebo, in a double-blind,
      randomized manner before and after a 3-month aerobic exercise program. Body
      composition was measured by magnetic resonance imaging. RESULTS: At baseline,
      caffeine ingestion was associated with a significant reduction (P < 0.05) in
      insulin sensitivity by a similar magnitude in the lean (33%), obese (33%), and
      type 2 diabetic (37%) groups in comparison with placebo. After exercise training,
      caffeine ingestion was still associated with a reduction (P < 0.05) in insulin
      sensitivity by a similar magnitude in the lean (23%), obese (26%), and type 2
      diabetic (36%) groups in comparison with placebo. Exercise was not associated
      with a significant increase in insulin sensitivity in either the caffeine or
      placebo trials, independent of group (P > 0.10). CONCLUSIONS: Caffeine
      consumption is associated with a substantial reduction in insulin-mediated
      glucose uptake independent of obesity, type 2 diabetes, and chronic exercise.

PMID- 15735190
TI  - Impact of early neonatal breast-feeding on psychomotor and neuropsychological
      development in children of diabetic mothers.
AB  - OBJECTIVE: In general, breast-feeding positively influences development of
      psychomotor function and cognition in children. Offspring of diabetic mothers
      (ODM) have delayed psychomotor and cognitive development. Recently, we observed a
      dose-dependent negative effect of early neonatal ingestion of breast milk from
      diabetic mothers (diabetic breast milk [DBM]) on the risk of overweight during
      early childhood. Here, we investigated the influence of early neonatal intake of
      DBM on neurodevelopment in ODM. RESEARCH DESIGN AND METHODS: A total of 242 ODM
      were evaluated for age of achieving major developmental milestones (Denver
      Developmental Scale) according to the volume of DBM ingested during the first
      week of life, using Kruskal-Wallis and Kaplan-Meier analysis. RESULTS: Children
      in the upper tertile of early neonatal ingestion of DBM achieved early
      psychomotor developmental milestones ("lifting head while prone," "following with
      eyes") earlier than those in lower tertiles (P = 0.002). In contrast, a delay in
      the onset of speaking was observed in children who had ingested larger volumes of
      DBM compared with those with lower DBM intake (P = 0.002). This negative impact
      of DBM ingestion was not confounded by birth characteristics, total milk intake,
      or socioeconomic/educational status. CONCLUSIONS: Our data indicate differential
      effects of early neonatal DBM ingestion on psychomotor and cognitive development.
      Ingesting larger compared with smaller volumes of DBM may normalize early
      psychomotor development in ODM but delays onset of speaking as a parameter
      indicative of cognitive development. This effect may result from qualitative
      alterations in the composition of DBM. Further studies are urgently recommended
      on the benefits and harms of breast-feeding in ODM.

PMID- 15735191
TI  - Increasing prevalence of gestational diabetes mellitus (GDM) over time and by
      birth cohort: Kaiser Permanente of Colorado GDM Screening Program.
AB  - OBJECTIVE: The prevalence of gestational diabetes mellitus (GDM) varies in direct
      proportion with the prevalence of type 2 diabetes in a given population or ethnic
      group. Given that the number of people with diabetes worldwide is expected to
      increase at record levels through 2030, we examined temporal trends in GDM among
      diverse ethnic groups. RESEARCH DESIGN AND METHODS: Kaiser Permanente of Colorado
      (KPCO) has used a standard protocol to universally screen for GDM since 1994.
      This report is based on 36,403 KPCO singleton pregnancies occurring between 1994
      and 2002 and examines trends in GDM prevalence among women with diverse ethnic
      backgrounds. RESULTS: The prevalence of GDM among KPCO members doubled from 1994
      to 2002 (2.1-4.1%, P < 0.001), with significant increases in all racial/ethnic
      groups. In logistic regression, year of diagnosis (odds ratio [OR] and 95% CI per
      1 year = 1.12 [1.09-1.14]), mother's age (OR per 5 years = 1.7 [1.6-1.8]) and
      ethnicity other than non-Hispanic white (OR = 2.1 [1.9-2.4]) were all
      significantly associated with GDM. Birth year remained significant (OR = 1.06, P
      = 0.006), even after adjusting for prior GDM history. CONCLUSIONS: This study
      shows that the prevalence of GDM is increasing in a universally screened
      multiethnic population. The increasing GDM prevalence suggests that the vicious
      cycle of diabetes in pregnancy initially described among Pima Indians may also be
      occurring among other U.S. ethnic groups.

PMID- 15735192
TI  - Early growth in offspring of diabetic mothers.
AB  - OBJECTIVE: By age 5 years, offspring of diabetic mothers (ODMs) are heavier and
      have altered glucose metabolism compared with offspring of mothers without
      diabetes (non-DMs). This study evaluates the growth pattern of ODMs before the
      age of 5 years. RESEARCH DESIGN AND METHODS: Anthropometric measures (z scores)
      from birth, 1.5 years, and 7.7 years in Pima Indian children were compared by
      maternal diabetes status. RESULTS: After adjustment for earlier gestational age
      at delivery (37.8 vs. 39.3 weeks, P < 0.01), ODMs were heavier at birth (z score
      birth weight 0.49 vs. -0.04, P < 0.01) than non-DMs. At age 1.5 years, ODMs were
      shorter than the non-DMs (z score = -0.24 vs. 0.12, P < 0.01) but their weight
      and relative weight (RW; weight adjusted for age, sex, and length or height) were
      similar. From birth to 1.5 years, ODMs showed significant "catch down" of weight
      compared with non-DMs (change in weight z score from birth to 1.5 years of ODMs
      and non-DMs was -0.56 and 0.12, respectively, P < 0.01). By age 7.7 years, ODMs
      were heavier (weight z score 0.89 vs. -0.07, P < 0.01) but had similar height as
      non-DMs. Differences in glucose and insulin concentrations at age 7.7 years were
      dependent on RW. CONCLUSIONS: ODMs had a dramatically different growth pattern
      from that of non-DMs. Gestational age-adjusted birth weight was higher. During
      the first 1.5 postnatal years, the change in weight z score and attained height
      were reduced. Subsequently, height caught up to that of non-DMs, while weight
      gain greatly exceeded that of non-DMs.

PMID- 15735193
TI  - Diabetes and the risk of lung cancer.
AB  - OBJECTIVE: The incidence of some cancers has been reported to be higher in
      diabetic patients than in the general population. We estimated the incidence of
      lung cancer in diabetic patients and investigated the hypothesis that the rate of
      lung cancer is different in diabetic compared with nondiabetic patients. RESEARCH
      DESIGN AND METHODS: Diabetic patients and age-, sex-, and general practice
      matched nondiabetic control subjects were identified from U.K. computerized
      general practice records (General Practice Research Database), and these records
      searched for any incident lung cancer, demographic details, and smoking status.
      Primary lung cancer incidence was calculated and rates compared between diabetic
      patients and nondiabetic control subjects using multivariate Cox regression,
      adjusting for age, sex, and smoking. The comparison was repeated for incident
      diabetic patients followed from diagnosis and after stratifying by diabetic
      treatment. RESULTS: The incidence of primary lung cancer in all 66,848 diabetic
      patients was 1.63 per 1,000 patient-years (95% CI 1.48-1.79) and 2.05 per 1,000
      patient-years (1.76-2.38) among diabetic patients followed from diagnosis. When
      compared with nondiabetic control subjects, the hazard ratio was 0.88 (0.79-0.97)
      for all diabetic patients and 1.12 (0.95-1.34) for those followed from diagnosis.
      When observation was truncated to allow for shorter life expectancy, the hazard
      ratio for the total cohort was 0.98 (0.84-1.13), and no association was found
      with any treatment group. CONCLUSIONS: No increased risk of lung cancer in
      diabetes was found. We hypothesize that the lower incidence may be partly due to
      shorter life expectancy.

PMID- 15735194
TI  - Adherence to statin therapy and LDL cholesterol goal attainment by patients with
      diabetes and dyslipidemia.
AB  - OBJECTIVE: The purpose of this study was to assess the relationship between
      adherence to statin therapy and LDL cholesterol goal achievement in patients with
      diabetes and dyslipidemia. RESEARCH DESIGN AND METHODS: The records of patients
      being medically treated for dyslipidemia in a managed care diabetes program from
      January 2001 to December 2002 were used to assess LDL cholesterol goal attainment
      (<100 mg/dl) and to compute a 9-month medication possession ratio (percentage of
      days when medication was available [MPR], beginning with the first prescription
      in the database). RESULTS: A total of 653 patient records was analyzed. The
      average MPR was significantly higher for men than for women (0.75 vs. 0.66, P <
      0.05). Overall, 44% (n = 290) of the patients achieved an LDL cholesterol level
      <100 mg/dl (52% of men and 37% of women, P < 0.05). A significant correlation
      emerged between MPR and plasma LDL cholesterol (P < 0.001), and MPR was
      significantly higher in patients who achieved the LDL cholesterol target than in
      those who did not (0.82 vs. 0.61, P < 0.05). CONCLUSIONS: Although statins are
      highly effective for decreasing LDL cholesterol levels in patients with
      dyslipidemia, including those with diabetes, failure to reach LDL cholesterol
      targets remains common. Adherence to statin therapy, as reflected by MPR, is
      closely related to LDL cholesterol goal attainment in patients with diabetes and
      dyslipidemia. The probability of goal achievement appears to increase
      substantially when the MPR is >0.80. Pharmacy records can be used to identify
      patients who are poorly compliant with statin therapy and at high risk for
      failure to attain LDL cholesterol goals. Because outcomes are directly related to
      patients' medication-taking behavior, when clinical goals (such as serum
      cholesterol levels) are not being reached, adherence should be the first item
      assessed by the clinician.

PMID- 15735195
TI  - Clinical inertia in response to inadequate glycemic control: do specialists
      differ from primary care physicians?
AB  - OBJECTIVE: Diabetic patients with inadequate glycemic control ought to have their
      management intensified. Failure to do so can be termed "clinical inertia."
      Because data suggest that specialist care results in better control than primary
      care, we evaluated whether specialists demonstrated less clinical inertia than
      primary care physicians. RESEARCH DESIGN AND METHODS: Using administrative data,
      we studied all non-insulin-requiring diabetic patients in eastern Ontario aged 65
      or older who had A1c results >8% between September 1999 and August 2000. Drug
      intensification was measured by comparing glucose-lowering drug regimens in 4
      month blocks before and after the elevated A1c test and was defined as 1) the
      addition of a new oral drug, 2) a dose increase of an existing oral drug, or 3)
      the initiation of insulin. Propensity score-based matching was used to control
      for confounding between groups. RESULTS: There were 591 patients with specialist
      care and 1,911 with exclusively primary care. In the matched cohorts, 45.1% of
      patients with specialist care versus 37.4% with primary care had drug
      intensification (P = 0.009). Most of this difference was attributed to
      specialists' more frequent initiation of insulin in response to elevated A1c.
      CONCLUSIONS: Fewer than one-half of patients with high A1c levels had
      intensification of their medications, regardless of specialty of their physician.
      Specialists were more aggressive with insulin initiation than primary care
      physicians, which may contribute to the lower A1c levels seen with specialist
      care. Interventions assisting patients and physicians to recognize and overcome
      clinical inertia should improve diabetes care in the population.

PMID- 15735196
TI  - Blood glucose and heart failure in nondiabetic patients.
AB  - OBJECTIVE: Nondiabetic patients were studied to determine whether increasing
      blood glucose is associated with subsequent incidence of heart failure. RESEARCH
      DESIGN AND METHODS: Baseline morning blood glucose determinations were evaluated
      with respect to subsequent heart failure using records from 20,810 nondiabetic
      patients. The onset of heart failure >1 year after initial glucose determinations
      was evaluated for patients who had 2-12 years of care. Patients were excluded if
      they had ever had the diagnosis of diabetes, had a diagnosis of heart failure <1
      year after initial blood glucose determinations, had a blood glucose
      determination >125 mg/dl, or used corticosteroids, loop diuretics, insulin, or
      oral hypoglycemics. RESULTS: Of the 20,810 patients studied, 916 patients
      developed heart failure over a total analysis time of 71,890 years at risk.
      Higher baseline morning glucose levels were associated with increased heart
      failure from 3.5% (glucose <90 mg/dl) to 3.8% (90-99 mg/dl) to 4.8% (100-109
      mg/dl) to 6% (110-125 mg/dl) over a mean 4- to 5-year evaluation period. The
      incidence rate increased from 7.5 cases per 1,000 person-years (glucose <90
      mg/dl) to 8.4 (90-99 mg/dl, NS) to 11.1 (100-109 mg/dl, P < 0.001) to 13.7 (110
      125 mg/dl, P < 0.0001), an 83% increase in heart failure if baseline glucose was
      >109 mg/dl compared with <90 mg/dl. A Cox proportionate hazards model including
      age, sex, BMI, creatinine, hypertension, lipids, smoking, medications, and
      coronary disease showed a progressive increase in hazard ratio from 1.25 (glucose
      90-99 mg/dl, P < 0.05) to 1.46 (100-109 mg/dl, P < 0.001) to 1.55 (110-125 mg/dl,
      P < 0.001) compared with glucose <90 mg/dl. Kaplan-Meier analysis showed
      increased glucose- associated risk with time. CONCLUSIONS: Patients with higher
      baseline blood glucose levels in the absence of diabetes and after adjustment for
      covariants have a significantly increased risk of heart failure.

PMID- 15735197
TI  - The association between glucose abnormalities and heart failure in the population
      based Reykjavik study.
AB  - OBJECTIVE: Diabetes is an independent risk factor for heart failure, whereas the
      relation between heart failure and abnormal glucose regulation (AGR) needs
      further evaluation. We studied this combination in the Reykjavik Study. RESEARCH
      DESIGN AND METHODS: The Reykjavik Study, a population-based cohort study during
      1967-1997, recruited 19,381 participants aged 33-84 years who were followed until
      2002. Oral glucose tolerance tests and chest X-rays were obtained from all
      participants. Cases were defined in accordance with World Health Organization
      criteria for type 2 diabetes or AGR (impaired glucose tolerance or impaired
      fasting glucose) and European Society of Cardiology guidelines for heart failure.
      RESULTS: The overall prevalence of type 2 diabetes and heart failure was 0.5% in
      men and 0.4% in women, while AGR and heart failure were found in 0.7% of men and
      0.6% of women. Among participants with normal glucose regulation, heart failure
      was diagnosed in 3.2% compared with 6.0 and 11.8% among those with AGR and type 2
      diabetes, respectively. The prevalence of type 2 diabetes in the age-group 45-65
      years increased in both sexes during the period (P for trend = 0.007). The odds
      ratio was 2.8 (95% CI 2.2-3.6) for the association between type 2 diabetes and
      heart failure and 1.7 (1.4-2.1) between AGR and heart failure. CONCLUSIONS: There
      is a strong association between any form of glucometabolic perturbation and heart
      failure. Future studies in this field should focus on all types of glucose
      abnormalities rather than previously diagnosed diabetes only.

PMID- 15735198
TI  - Associations of mortality and diabetes complications in patients with type 1 and
      type 2 diabetes: early treatment diabetic retinopathy study report no. 27.
AB  - OBJECTIVE: Diabetes is a leading cause of morbidity and mortality. The purpose of
      this study is to assess the associations between diabetes complications and
      mortality in the Early Treatment Diabetic Retinopathy Study (ETDRS). RESEARCH
      DESIGN AND METHODS: We examined demographic, clinical, and laboratory
      characteristics of the 3,711 subjects enrolled in the ETDRS, a randomized
      controlled clinical trial designed to evaluate the role of laser photocoagulation
      and aspirin therapy for diabetic retinopathy. The outcome assessed was all-cause
      mortality. Multivariable Cox proportional hazards regression was used to assess
      associations between diabetes complications and mortality for type 1 and type 2
      diabetes separately. RESULTS: The 5-year estimates of all-cause mortality were
      5.5 and 18.9% for patients with type 1 and type 2 diabetes, respectively. In
      patients with type 1 diabetes, amputation (hazard ratio [HR] 5.08 [95% CI 2.06
      12.54]) and poor visual acuity (1.74 [1.10-2.75]) remained significantly
      associated with mortality, after adjusting for other diabetes complications and
      baseline characteristics. In patients with type 2 diabetes, macrovascular disease
      and worsening levels of nephropathy, neuropathy, retinopathy, and visual acuity
      are associated with progressively increasing risks of mortality, after
      controlling for other baseline risk factors. CONCLUSIONS: Amputation is the
      strongest predictor for mortality in patients with type 1 diabetes. All
      complications independently predict mortality in patients with type 2 diabetes.
      There is an increased risk for mortality as the degree of each complication
      worsens. Additional studies are needed to investigate the effectiveness of
      tertiary prevention to decrease mortality in these patients.

PMID- 15735199
TI  - Assessing psychosocial distress in diabetes: development of the diabetes distress
      scale.
AB  - OBJECTIVE: The purpose of this study was to describe the development of the
      Diabetes Distress Scale (DDS), a new instrument for the assessment of diabetes
      related emotional distress, based on four independent patient samples. RESEARCH
      DESIGN AND METHODS: In consultation with patients and professionals from multiple
      disciplines, a preliminary scale of 28 items was developed, based a priori on
      four distress-related domains: emotional burden subscale, physician-related
      distress subscale, regimen-related distress subscale, and diabetes-related
      interpersonal distress. The new instrument was included in a larger battery of
      questionnaires used in diabetes studies at four diverse sites: waiting room at a
      primary care clinic (n = 200), waiting room at a diabetes specialty clinic (n =
      179), a diabetes management study program (n = 167), and an ongoing diabetes
      management program (n = 158). RESULTS: Exploratory factor analyses revealed four
      factors consistent across sites (involving 17 of the 28 items) that matched the
      critical content domains identified earlier. The correlation between the 28-item
      and 17-item scales was very high (r = 0.99). The mean correlation between the 17
      item total score (DDS) and the four subscales was high (r = 0.82), but the
      pattern of interscale correlations suggested that the subscales, although not
      totally independent, tapped into relatively different areas of diabetes-related
      distress. Internal reliability of the DDS and the four subscales was adequate
      (alpha > 0.87), and validity coefficients yielded significant linkages with the
      Center for Epidemiological Studies Depression Scale, meal planning, exercise, and
      total cholesterol. Insulin users evidenced the highest mean DDS total scores,
      whereas diet-controlled subjects displayed the lowest scores (P < 0.001).
      CONCLUSIONS: The DDS has a consistent, generalizable factor structure and good
      internal reliability and validity across four different clinical sites. The new
      instrument may serve as a valuable measure of diabetes-related emotional distress
      for use in research and clinical practice.

PMID- 15735200
TI  - Effects of pramlintide on postprandial glucose excursions and measures of
      oxidative stress in patients with type 1 diabetes.
AB  - OBJECTIVE: Oxidative stress has been shown to be increased in the postprandial
      period in patients with diabetes and has been implicated in the pathogenesis of
      micro- and macrovascular complications. The aim of this post hoc analysis was to
      assess the effects of pramlintide, an amylin analog shown to reduce postprandial
      glucose excursions in patients with diabetes, on markers of oxidative stress in
      the postprandial period. RESEARCH DESIGN AND METHODS: In a randomized, single
      blind, placebo-controlled, crossover study, 18 evaluable subjects with type 1
      diabetes underwent two standardized breakfast meal tests and received pramlintide
      or placebo in addition to their preprandial insulin. The plasma concentrations of
      glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL],
      and total radical-trapping antioxidant parameter [TRAP]) were measured at
      baseline and during the 4-h postprandial period. RESULTS: Compared with placebo,
      pramlintide treatment significantly reduced postprandial excursions of glucose,
      nitrotyrosine, and ox-LDL and prevented a decline in TRAP (P < 0.03 for all
      comparisons). Correlation analyses adjusted for treatment revealed a significant
      association between postprandial mean incremental area under the curve from 0 to
      4 h (AUC(0-4 h)) for glucose and postprandial mean incremental AUC(0-4 h) for
      each measure of oxidative stress (r = 0.75, 0.54, and -0.63 for nitrotyrosine, ox
      LDL, and TRAP, respectively; P < 0.001 for all correlations). CONCLUSIONS: These
      findings indicate that the postprandial glucose-lowering effect of pramlintide in
      type 1 diabetes is associated with a significant reduction in postprandial
      oxidative stress.

PMID- 15735201
TI  - Youth type 2 diabetes: insulin resistance, beta-cell failure, or both?
AB  - OBJECTIVE: This study evaluates insulin sensitivity, pancreatic beta-cell
      function (BCF), and the balance between the two in youth with type 2 diabetes and
      assesses the relationship of diabetes duration and HbA(1c) to insulin sensitivity
      and BCF. RESEARCH DESIGN AND METHODS: The subjects were 14 adolescents with type
      2 diabetes and 20 obese control subjects of comparable age, BMI, body
      composition, and puberty. Insulin sensitivity was evaluated with a 3-h
      hyperinsulinemic (80 mU . m(-2) . min(-1)) euglycemic clamp. First-phase insulin
      secretion (FPIS) and second-phase insulin secretion (SPIS) were evaluated with a
      2-h hyperglycemic (12.5 mmol/l) clamp. Fasting glucose rate of appearance was
      determined with the use of [6,6-(2)H(2)]glucose. RESULTS: Fasting glucose rate of
      appearance was higher in type 2 diabetic patients than in obese control subjects
      (16.5 +/- 1.1 vs. 12.3 +/- 0.5 micromol . kg(-1) . min(-1); P = 0.002). Insulin
      sensitivity was lower in type 2 diabetic patients than in obese control subjects
      (1.0 +/- 0.1 vs. 2.0 +/- 0.2 micromol . kg(-1) . min(-1) per pmol/l; P = 0.001).
      Fasting insulin was higher in type 2 diabetic patients than in obese control
      subjects (289.8 +/- 24.6 vs. 220.2 +/- 18.0 pmol/l; P = 0.007), and FPIS and SPIS
      were lower (FPIS: 357.6 +/- 42.0 vs. 1,365.0 +/- 111.0 pmol/l; SPIS: 652.2 +/-
      88.8 vs. 1,376.4 +/- 88.8 pmol/l; P < 0.001 for both). The glucose disposition
      index (GDI = insulin sensitivity x FPIS) was approximately 86% lower in type 2
      diabetic patients than in obese control subjects. HbA(1c) correlated with FPIS (r
      = -0.61, P = 0.025) with no relationship to insulin sensitivity. CONCLUSIONS:
      Despite the impairment in both insulin sensitivity and BCF in youth with type 2
      diabetes, the magnitude of the derangement is greater in BCF than insulin
      sensitivity when compared with that in obese control subjects. The inverse
      relationship between BCF and HbA(1c) may either reflect the impact of
      deteriorating BCF on glycemic control or be a manifestation of a glucotoxic
      phenomenon on BCF. Future studies in youth type 2 diabetes should target the
      natural course of beta-cell failure and means of retarding and/or preventing it.

PMID- 15735202
TI  - Identification of Amadori-modified plasma proteins in type 2 diabetes and the
      effect of short-term intensive insulin treatment.
AB  - OBJECTIVE: Growing evidence supports that nonenzymatic glycation products may
      cause hyperglycemia-induced diabetes complications. Amadori-modified proteins are
      the intermediate products of nonenzymatic glycation and constitute the forms of
      glycated proteins in diabetes. The objective of the current study was to utilize
      two-dimensional gel electrophoresis, Western blot, and mass spectrometry to
      identify Amadori-modified plasma proteins in type 2 diabetic patients with poor
      glycemic control and assess the impact of short-term insulin treatment on the
      glycation of these proteins. RESEARCH DESIGN AND METHODS: We compared eight type
      2 diabetic subjects (aged 56 +/- 3 years and BMI 29.7 +/- 0.9 kg/m(2)) with an
      average diabetes duration of 8.5 years (range 3-19) with equal numbers of weight
      matched (aged 56 +/- 2 years and BMI 30.1 +/- 10.0 kg/m(2)) and lean (aged 58 +/-
      2 years and BMI 25 +/- 00.5 kg/m(2)) nondiabetic subjects who have no first
      degree relatives with diabetes. Two separate blood samples were collected from
      the type 2 diabetic subjects, one following 2 weeks of withdrawal of all
      antidiabetic medications (T(2)D-; plasma glucose 12.6 +/- 1.0 mmol/l) and another
      following 10 days of intensive insulin treatment (T(2)D+; plasma glucose 5.5 +/-
      0.2 mmol/l). Plasma proteins were separated using single and two-dimensional gel
      electrophoresis. Western blot analysis was performed, and several proteins, which
      reacted with the Amadori-antibody (1-deoxyfructosyl lysine), were identified by
      tandem mass spectrometry. RESULTS: No significant differences in the glycation of
      proteins between the obese and lean groups were noted, but type 2 diabetic
      patients had several proteins with higher glycation than the control groups. We
      identified 12 plasma proteins with reduced reaction to the anti-Amadori antibody
      upon intensive insulin treatment. A significant (P < 0.03) difference in Amadori
      modification was observed between the T(2)D- and control subjects for all these
      proteins except the Ig light chain. Insulin treatment reduced Amadori
      modification of albumin (23.2%, P < 0.02), fibrin (34.6%, P < 0.001), Ig heavy
      chain constant region (20.7%, P < 0.05), transferrin (25.4%, P < 0.04), and Ig
      light chain (13%, P < 0.02). In addition, Western blot analysis of two
      dimensional gel electrophoresis identified alpha-fibrinogen precursor, beta
      fibrinogen precursor, fibrinogen gamma-B chain precursor, hemopexin, vitamin D
      binding protein, and serine protease inhibitor as proteins with a reduced
      reaction to anti-Amadori antibody upon intensive insulin treatment. CONCLUSIONS:
      The current approach offers the opportunity to identify Amadori modification of
      many proteins that may cause functional alterations and offers the potential for
      monitoring short-term glycemic control in diabetic patients.

PMID- 15735203
TI  - Autoantibodies against oxidized LDLs and atherosclerosis in type 2 diabetes.
AB  - OBJECTIVE: The aim of our study was to examine, in type 2 diabetic patients, the
      relationship between autoantibodies against oxidatively modified LDL (oxLDL Ab)
      and two indexes of atherosclerosis, intimal-medial thickness of the common
      carotid artery (CCA-IMT), which reflects early atherosclerosis, and the ankle
      brachial index (ABI), which reflects advanced atherosclerosis. RESEARCH DESIGN
      AND METHODS: Thirty newly diagnosed type 2 diabetic patients, 30 type 2 diabetic
      patients with long duration of disease, and 56 control subjects were studied. To
      detect oxLDL Ab, the ImmunoLisa Anti-oxLDL Antibody ELISA was used. ABI was
      estimated at rest by strain-gauge plethysmography. Carotid B-mode imaging was
      performed on a high-resolution imaging system (ATL HDI 5000). RESULTS: In
      patients with long duration of disease, IgG oxLDL Ab were significantly higher
      and ABI significantly lower compared with the other two groups. We found a
      correlation between IgG oxLDL Ab and CCA-IMT in all diabetic patients. A
      significant inverse correlation between IgG oxLDL Ab and ABI only in patients
      with long duration of disease was seen, demonstrating a close relationship
      between these autoantibodies and advanced atherosclerosis. CONCLUSIONS: IgG OxLDL
      Ab may be markers of the advanced phase of the atherosclerotic process and the
      response of the immunological system to the oxLDL, which are present within
      atherosclerotic lesions.

PMID- 15735204
TI  - Reduced prevalence of limited joint mobility in type 1 diabetes in a U.K. clinic
      population over a 20-year period.
AB  - OBJECTIVE: Limited joint mobility (LJM), one of the earliest clinically apparent
      long-term complications of type 1 diabetes, is a risk marker for subsequent
      microvascular complications. We hypothesize that the prevalence of LJM may have
      decreased during the past two decades due to improved standards of glycemic
      control. RESEARCH DESIGN AND METHODS: A single observer performed a survey in 204
      consecutive patients with type 1 diabetes (106 men and 98 women, age 27 +/- 1
      years, HbA(1c) 8.3 +/- 0.1%, duration of diabetes 14.5 +/- 0.8 years, insulin
      dose 63 +/- 2 units/day). We used the same examination method and criteria for
      assessment of LJM as used by us in an earlier study in 1981-1982. RESULTS: The
      prevalence of LJM has fallen from 43 to 23% between the 1980s and 2002 (P <
      0.0001). The relative risk for LJM in 2002 compared with the 1981-1982 cohort was
      0.53 (0.40 < RR < 0.72, P < 0.0001). The prevalence of LJM was increased with
      longer duration of diabetes (<10 years, 13%; 10-20 years, 19%; 20-29 years, 30%;
      >30 years, 65%; P < 0.001). The relative risk for those with a mean HbA(1c) <7%
      in 2002 was 0.3 (0.1 < RR < 1.2, P = 0.05) when compared with those with mean
      HbA(1c) >7%. CONCLUSIONS: The present study confirms the hypothesis that the
      prevalence of LJM is lower than 20 years ago and that improved standards of
      glycemic control and diabetes care may have contributed to this occurrence. Joint
      limitation in type 1 diabetes is strongly associated with duration of diabetes.
      The presence of LJM remains a common and important clinical marker for subsequent
      microvascular disease and can be a useful clinical tool for identification of
      patients at increased risk.

PMID- 15735205
TI  - Twice-weekly progressive resistance training decreases abdominal fat and improves
      insulin sensitivity in older men with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the influence of a twice-weekly progressive resistance
      training (PRT) program, without a concomitant weight loss diet, on abdominal fat
      and insulin sensitivity in older men with type 2 diabetes. RESEARCH DESIGN AND
      METHODS: Nine older men (aged 66.6 +/- 3.1) with type 2 diabetes participated in
      a 16-week PRT supervised program (50-80% of the one repetition maximum), for all
      main muscle groups. Basal glycemia, HbA(1c), diet, habitual physical activity,
      body composition, and upper/lower maximal strength were measured. Insulin
      sensitivity was determined according to Bergman's minimal model procedure and
      abdominal fat was obtained by computed tomography. The measurements were taken 4
      weeks before training (-4), immediately before training (0), and at 8-week
      intervals (i.e., weeks 8 and 16) during the 16-week training period. RESULTS: No
      significant variation was observed in any of the above selected parameters during
      the 4-week control period. After PRT, both leg and arm maximal strength increased
      significantly by 17.1 and 18.2%, respectively. Visceral and subcutaneous
      abdominal fat decreased significantly by 10.3% (from 249.5 +/- 97.9 to 225.6 +/-
      96.6 cm(3), P < 0.01) and by 11.2% (from 356.0 +/- 127.5 to 308.6 +/- 118.8
      cm(3), P < 0.01), respectively, while no changes were observed in body mass. PRT
      significantly increased insulin sensitivity by 46.3% (from 2.0 +/- 1.2 to 2.8 +/-
      1.6 . 10(4) . min(-1) . muU(-1) . ml(-1), P < 0.01), whereas it significantly
      decreased (-7.1%, P < 0.05) fasting blood glucose (from 146.6 +/- 28.3 to 135.0
      +/- 29.3 mg/dl). Finally, a 15.5% increase in energy intake (from 2,287.1 +/-
      354.7 to 2,619.0 +/- 472.1 kcal/day, P < 0.05) was observed. CONCLUSIONS: Two
      sessions per week of PRT, without a concomitant weight loss diet, significantly
      improves insulin sensitivity and fasting glycemia and decreases abdominal fat in
      older men with type 2 diabetes.

PMID- 15735206
TI  - Diabetes, glucose, insulin, and heart rate variability: the Atherosclerosis Risk
      in Communities (ARIC) study.
AB  - OBJECTIVE: To describe the progression of autonomic impairment among individuals
      with diabetes and pre-diabetic metabolic impairments. RESEARCH DESIGN AND
      METHODS: We investigated the consequence of diabetes and pre-diabetic metabolic
      impairments on the 9-year change in heart rate variability (HRV) in a population
      based cohort of 6,245 individuals aged 45-64 years at baseline and cross
      sectional associations among 9,940 individuals. RESULTS: Diabetic subjects had a
      more rapid temporal decrease in HRV conditional on baseline HRV than nondiabetic
      subjects. Adjusted mean annual changes (95% CI) (ms/year) in the SD of all normal
      to-normal R-R intervals were -0.65 (-0.69 to -0.61) for those with normal fasting
      glucose vs. -0.95 (-1.09 to -0.81) for diabetic subjects, in root mean square of
      successive differences in normal-to-normal R-R intervals -0.35 (-0.39 to -0.30)
      vs. -0.66 (-0.82 to -0.51), and in R-R interval 6.70 (6.37-7.04) vs. 3.89 (2.72
      5.05). While we found cross-sectional associations between decreased HRV and
      diabetes and nondiabetic hyperinsulinemia and a weak inverse association with
      fasting glucose, neither impaired fasting glucose nor nondiabetic
      hyperinsulimenia was associated with a measurably more rapid decline in HRV than
      normal. CONCLUSIONS: Cardiac autonomic impairment appears to be present at early
      stages of diabetic metabolic impairment, and progressive worsening of autonomic
      cardiac function over 9 years was observed in diabetic subjects. The degree to
      which pre-diabetic metabolic impairments in insulin and glucose metabolism
      contribute to decreases in cardiac autonomic function remains to be determined.

PMID- 15735207
TI  - A prospective study on the prevalence of metabolic syndrome among healthy french
      families: two cardiovascular risk factors (HDL cholesterol and tumor necrosis
      factor-alpha) are revealed in the offspring of parents with metabolic syndrome.
AB  - OBJECTIVE: The purpose of this study was to estimate the longitudinal variation
      of prevalence of metabolic syndrome within French families and to observe
      biological parameters involved in cardiovascular disease among their offspring.
      RESEARCH DESIGN AND METHODS: Three hundred seventy-one apparently healthy
      families (1,366 individuals) taken from the STANISLAS cohort were studied. The
      subjects were examined at two time points with a 5-year interval (t(0) and
      t(+5)). The crude prevalence of metabolic syndrome was assessed among parents
      according to the National Cholesterol Education Program Adult Treatment Panel III
      (NCEP ATP) definition. RESULTS: The prevalence of metabolic syndrome was 5.9% in
      men and 2.1% in women at t(0), rising to 7.2 and 5.4% in men and women,
      respectively, at t(+5). Children of parents having metabolic syndrome showed
      higher levels of tumor necrosis factor-alpha (TNF-alpha), whereas their HDL
      cholesterol and apolipoprotein (apo) E concentrations were lower compared with
      those of age- and sex-matched control subjects (P </= 0.05). When applying NCEP
      ATP definitions that included either antihypertensive drugs only or all the drugs
      involved in metabolic syndrome, we found that the three parameters shared by the
      three different versions of the definition were TNF-alpha, HDL cholesterol, and
      an interaction between alcohol consumption and parental metabolic syndrome on HDL
      cholesterol concentration. CONCLUSIONS: Metabolic syndrome increases with age in
      supposedly healthy families from the STANISLAS cohort. In offspring of affected
      people, it seems to be predictive of higher values of TNF-alpha and low HDL
      cholesterol levels, which are two major cardiovascular factors. Therefore, in
      terms of prevention, it is important to identify and follow subjects with
      metabolic syndrome as well as their offspring, even in apparently healthy
      populations, to enable early disease management.

PMID- 15735208
TI  - Presence of the metabolic syndrome does not impair coronary collateral vessel
      formation in patients with documented coronary artery disease.
AB  - OBJECTIVE: The metabolic syndrome confers an increased risk for cardiovascular
      morbidity and mortality. The presence of coronary collaterals may have beneficial
      effects during myocardial ischemia and may improve cardiovascular outcome in
      patients with coronary artery disease. Impaired collateral formation could be one
      of the reasons for the increased cardiovascular risk in patients with the
      metabolic syndrome. The aim of the present study was to determine the influence
      of the metabolic syndrome and insulin resistance on the presence of coronary
      collaterals. RESEARCH DESIGNS AND METHODS: We conducted a cross-sectional study
      in 227 patients referred for elective percutaneous transluminal coronary
      angioplasty to the University Medical Centre Utrecht. The metabolic syndrome was
      diagnosed according to Adult Treatment Panel III, and homeostasis model
      assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity
      check index (QUICKI) were used to quantify insulin resistance. Coronary
      collaterals were graded with Rentrop's classification. Rentrop grade >/=1
      indicated the presence of collaterals. Results were adjusted for age, sex, and
      severity of coronary artery disease. RESULTS: A total of 103 patients (45%) were
      diagnosed with the metabolic syndrome. There was no association between the
      metabolic syndrome and the presence of coronary collateral formation (odds ratio
      [OR] 1.2 [95% CI 0.7-2.0]). Also, the degree of insulin resistance was not
      related to the presence of coronary collaterals. The OR for HOMA-IR (highest
      versus lowest tertile) was 0.7 (0.3-1.5) and for QUICKI (lowest versus highest
      tertile) 0.8 (0.4-1.6). CONCLUSIONS: The metabolic syndrome and insulin
      resistance are not related to the presence of coronary collaterals in patients
      with documented coronary artery disease.

PMID- 15735209
TI  - Cardiovascular disease in U.S. patients with metabolic syndrome, diabetes, and
      elevated C-reactive protein.
AB  - OBJECTIVE: C-reactive protein (CRP) independently predicts cardiovascular disease
      (CVD); whether it can stratify risk in those with metabolic syndrome and diabetes
      is not well documented. We evaluated whether elevated CRP levels modify the
      relationship of metabolic syndrome and diabetes with CVD in U.S. adults. RESEARCH
      DESIGN AND METHODS: In a cross-sectional study of 3,873 subjects (weighted to 156
      million) aged >/=18 years participating in the National Health and Nutrition
      Examination Survey 1999-2000, subjects were classified as having diabetes,
      metabolic syndrome according to modified National Cholesterol Education Program
      criteria, or neither condition by low (<1 mg/l), intermediate (1-3 mg/l), or high
      (>3 mg/l) CRP levels. Logistic regression examined the odds of CVD by disease
      condition and CRP group. RESULTS: After adjusting for age, sex, smoking, and
      total cholesterol, compared with those with neither metabolic syndrome nor
      diabetes and low CRP levels, the odds of CVD were 1.99 (95% CI 1.10-3.59) for
      those with no disease and high CRP levels and 2.67 (1.30-5.48) for those with
      metabolic syndrome and intermediate CRP. Persons with metabolic syndrome but high
      CRP had an odds ratio (OR) of 3.33 (1.80-6.16), similar to those with diabetes
      and low CRP (3.21 [1.27-8.09]). The likelihood of CVD was highest in those with
      diabetes who had intermediate CRP levels (6.01 [2.54-14.20]) and in those with
      diabetes and high CRP (7.73 [3.99-14.95]). CONCLUSIONS: In this cross-sectional
      analysis, CVD is more common in those with metabolic syndrome or diabetes who
      have elevated CRP. Stratification by CRP may add prognostic information in
      patients with metabolic syndrome or diabetes.

PMID- 15735210
TI  - Can adoption of regular exercise later in life prevent metabolic risk for
      cardiovascular disease?
AB  - OBJECTIVE: To determine the impact of chronic exercise training initiated later
      in life upon development of metabolic markers of cardiovascular disease risk.
      RESEARCH DESIGN AND METHODS: Two inception cohorts of previously sedentary
      healthy adults aged 55-75 years at baseline (1989), one initiating regular
      supervised physical exercise training and the other a geographical similar
      sedentary control, were assessed for anthropometric, biochemical, and clinical
      markers of the metabolic syndrome and comorbidity over 10 years. RESULTS: At
      baseline, active individuals aged 68 years compared with sedentary individuals
      aged 67 years had similar fitness levels (5.7 vs. 5.8 metabolic equivalents). At
      follow-up, complete data were obtained for 161 active and 136 sedentary subjects.
      Drop out occurred primarily because of failure to adhere to the exercise regimen
      and poor physical health for active and sedentary individuals, respectively. More
      metabolic abnormalities were seen in the sedentary group than in the active group
      for one or two (64 vs. 36%, P < 0.001) and three or more (35 vs. 22%, P < 0.003)
      abnormalities, respectively. In those assessed at follow-up, the sedentary group
      compared with the active group had lower fitness levels (5.0 [13.8% decrease] vs.
      5.9 [3.5% increase] metabolic equivalents), had a greater likelihood of a
      positive exercise electrocardiogram or symptom (32 vs. 10%, P < 0.001), and had
      more comorbid conditions (Charlson Comorbidity Index score 0.9 vs. 0.4, P <
      0.01). CONCLUSIONS: Higher fitness achieved over 10 years of regular exercise
      training in older adults was associated with reduced development of metabolic
      risk factors for cardiovascular disease, fewer exercise-induced cardiac
      abnormalities, and reduced comorbidity.

PMID- 15735211
TI  - Endothelial-dependent vasodilation and incidence of type 2 diabetes in a
      population of healthy postmenopausal women.
AB  - OBJECTIVE: Both postmenopausal state and diabetes are associated with endothelial
      dysfunction and are well-known risk factors for atherosclerosis. However, the
      relationship of endothelium-dependent vasodilation and diabetes has never been
      prospectively evaluated. This study provided the opportunity to assess the
      association between endothelial vasodilation function and the incidence of
      diabetes in a cohort of apparently healthy postmenopausal women. RESEARCH DESIGN
      AND METHODS: We conducted a prospective cohort study that began in 1997 with 840
      apparently healthy, nonobese, postmenopausal women, aged 53 +/- 6 years,
      initially with normal glucose tolerance at the oral glucose tolerance test. All
      participants were followed up for a mean period of 3.9 +/- 0.7 years (range 0.5
      6.9). Endothelial function was measured as flow-mediated dilation (FMD) of the
      brachial artery, using high-resolution ultrasound. RESULTS: There were no
      significant differences in demographic, blood pressure, and biochemical profiles
      among each tertile group at baseline or at follow-up review. During follow-up,
      102 women developed type 2 diabetes. The adjusted relative risk (RR) for women
      with FMD </=4.3 (lowest tertile) was 5.87 (95% CI 4.34-8.10) versus women with
      FMD >/=5.6 (highest tertile reference). Each 1-unit decrease of FMD was
      associated with a significant 32% (22-48%) increase in the multiple-adjusted RR
      of incident diabetes. CONCLUSIONS: These prospective data indicate a significant
      increase in the RR of diabetes with each unit decrease of FMD. This could suggest
      that an impaired endothelial function may play a fundamental role in
      diabetogenesis in postmenopausal women.

PMID- 15735212
TI  - Hypoglycemia detection rate differs among blood glucose monitoring sites.

PMID- 15735213
TI  - Alternate-site testing is reliable in children and adolescents with type 1
      diabetes, except at the forearm for hypoglycemia detection.

PMID- 15735214
TI  - Chromium supplementation does not improve glucose tolerance, insulin sensitivity,
      or lipid profile: a randomized, placebo-controlled, double-blind trial of
      supplementation in subjects with impaired glucose tolerance.

PMID- 15735215
TI  - Inflammatory markers and diabetic retinopathy in type 1 diabetes.

PMID- 15735216
TI  - Metabolic syndrome and insulin resistance in normal glucose tolerant brazilian
      adolescents with family history of type 2 diabetes.

PMID- 15735217
TI  - Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis
      of prospective observational studies.
AB  - OBJECTIVE: This meta-analysis was undertaken to obtain insight regarding the
      shape and strength of the relationship between alcohol consumption and the risk
      of type 2 diabetes, the effects of adjustment for confounders, and the effect of
      modification by type 2 diabetes definition, sex, and BMI. RESEARCH DESIGN AND
      METHODS: The 15 original prospective cohort studies that were included comprise
      11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average,
      were followed for 12 years. RESULTS: After pooling the data, a U-shaped
      relationship was found. Compared with nonconsumers, the relative risk (RR) for
      type 2 diabetes in those who consumed </=6 g/day alcohol was 0.87 (95% CI 0.79
      0.95). For the moderate consumption ranges of 6-12, 12-24, and 24-48 g/day, RRs
      of 0.70 (0.61-0.79), 0.69 (0.58-0.81), and 0.72 (0.62-0.84) were found,
      respectively. The risk of type 2 diabetes in heavy drinkers (>/=48 g/day) was
      equal to that in nonconsumers (1.04 [0.84-1.29]). In general, nonsignificant
      trends for larger RR reduction associated with moderate alcohol consumption were
      observed for women compared with men, for crude compared with multivariate
      adjusted analyses, and for studies that used self-reports instead of testing for
      type 2 diabetes definition. No differences in RR reductions were found between
      individuals with low or high BMI. CONCLUSIONS: The present evidence from
      observational studies suggests an approximately 30% reduced risk of type 2
      diabetes in moderate alcohol consumers, whereas no risk reduction is observed in
      consumers of >/=48 g/day.

PMID- 15735218
TI  - The effects of type 1 diabetes on cognitive performance: a meta-analysis.
AB  - OBJECTIVE: To investigate the exact nature and magnitude of cognitive impairments
      in patients with type 1 diabetes and the possible association with other disease
      variables, such as recurrent episodes of hypoglycemia and metabolic control.
      RESEARCH DESIGN AND METHODS: MedLine and PsycLit search engines were used to
      identify studies on cognitive performance in patients with type 1 diabetes.
      Effect sizes (Cohen's d), which are the standardized differences between the
      experimental and the control group, were calculated. In the meta-analysis, a
      combined d value was calculated, expressing the magnitude of associations across
      studies. RESULTS: A total of 33 studies were identified that met the inclusion
      criteria. Compared with nondiabetic control subjects, the type 1 diabetic group
      demonstrated a significantly lowered performance on the following cognitive
      domains: intelligence (d = -0.7), speed of information processing (d = -0.3),
      psychomotor efficiency (d = -0.6), visual (d = -0.4) and sustained attention (d =
      -0.3), cognitive flexibility (d = -0.5), and visual perception (d = -0.4).
      Lowered cognitive performance in diabetic patients appeared to be associated with
      the presence of microvascular complications but not with the occurrence of severe
      hypoglycemic episodes or with poor metabolic control. CONCLUSIONS: In patients
      with type 1 diabetes, cognitive dysfunction is characterized by a slowing of
      mental speed and a diminished mental flexibility, whereas learning and memory are
      spared.The magnitude of the cognitive deficits is mild to moderate, but even mild
      forms of cognitive dysfunction might hamper everyday activities since they can be
      expected to present problems in more demanding situations.

PMID- 15735220
TI  - Diabetic nephropathy.

PMID- 15735219
TI  - A systematic review of drug therapy to delay or prevent type 2 diabetes.
AB  - OBJECTIVE: To systematically review the evidence for the prevention of type 2
      diabetes by pharmacological therapies. RESEARCH DESIGN AND METHODS: Randomized
      controlled trials and cohort studies examining the effect of oral hypoglycemic
      agents, antiobesity agents, antihypertensive agents, statins, fibrates, and
      estrogen on the incidence of type 2 diabetes were identified from MEDLINE,
      EMBASE, the Cochrane Controlled Trials Registry, and searches of reference lists.
      Two reviewers independently assessed studies for inclusion and performed data
      extraction. RESULTS: Ten studies of oral hypoglycemic agents and 15 studies of
      nonoral hypoglycemic agents were found. Oral hypoglycemic agents and orlistat are
      the only drugs that have been studied in randomized controlled trials with
      diabetes incidence as the primary end point. In the largest studies of 2.5-4.0
      years' duration, metformin (relative risk [RR] 0.69, 95% CI 0.57-0.83), acarbose
      (0.75, 0.63-0.90), troglitazone (0.45, 0.25-0.83), and orlistat (hazard ratio
      [HR] 0.63, 95% CI 0.46-0.86) have all been shown to decrease diabetes incidence
      compared with placebo; however, follow-up rates varied from 43 to 96%. Current
      evidence for statins, fibrates, antihypertensive agents, and estrogen is
      inconclusive. In addition, the critical question of whether drugs are preventing,
      or simply delaying, onset of diabetes remains unresolved. CONCLUSIONS: Currently,
      no single agent can be definitively recommended for diabetes prevention. Future
      studies should be designed with diabetes incidence as the primary outcome and
      should be of sufficient duration to differentiate between genuine diabetes
      prevention as opposed to simple delay or masking of this condition.

PMID- 15735221
TI  - Cholestatic hepatitis associated with repaglinide.

PMID- 15735222
TI  - B-type natriuretic peptide in type 2 diabetes: the influence of chronic renal
      failure and food.

PMID- 15735223
TI  - Cerebral edema without ketoacidosis or hyperosmolar coma in a 16-year- old boy.

PMID- 15735224
TI  - Adipocytokines as a novel target for the anti-inflammatory effect of atorvastatin
      in patients with type 2 diabetes.

PMID- 15735226
TI  - Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the
      DIAD study.

PMID- 15735225
TI  - Plasma adiponectin concentrations are independently predicted by fat insulin
      sensitivity in women and by muscle insulin sensitivity in men.

PMID- 15735227
TI  - Sexual dysfunction in women with the metabolic syndrome.

PMID- 15735228
TI  - Replacement of valsartan and candesartan by telmisartan in hypertensive patients
      with type 2 diabetes: metabolic and antiatherogenic consequences.

PMID- 15735229
TI  - High-dose glibenclamide can replace insulin therapy despite transitory diarrhea
      in early-onset diabetes caused by a novel R201L Kir6.2 mutation.

PMID- 15735230
TI  - Positive correlation of galanin with glucose in type 2 diabetes.

PMID- 15735231
TI  - Four-digit insulin dosing code: a simple solution for insulin dosing error.

PMID- 15735232
TI  - INSULOT: a cellular phone-based edutainment learning tool for children with type
      1 diabetes.

PMID- 15735233
TI  - The burden of treatment failure in type 2 diabetes: response to Brown et al.

PMID- 15735235
TI  - Antihypertensive therapy and incidence of type 2 diabetes in an elderly cohort:
      response to Padwal et al.

PMID- 15735237
TI  - Continuous subcutaneous insulin infusion versus multiple daily injections: the
      impact of baseline A1c: response to Retnakaran et al.

PMID- 15735238
TI  - The role of fibroblast growth factor 23 in renal disease.

PMID- 15735239
TI  - Ren sanus in corpore sano: the myth of the inexorable decline of renal function
      with senescence.

PMID- 15735240
TI  - Why patients with progressing kidney disease are referred late to the
      nephrologist: on causes and proposals for improvement.

PMID- 15735241
TI  - Biochemical risk markers: a novel area for better prediction of renal risk?

PMID- 15735242
TI  - Renin-angiotensin blockade reduces serum free testosterone in middle-aged men on
      haemodialysis and correlates with erythropoietin resistance.
AB  - BACKGROUND: There are conflicting reports about the importance of the renin
      angiotensin system (RAS) on erythropoietin (Epo) sensitivity in haemodialysis
      patients, but the role of gender has not been studied specifically. The
      hypothesis underlying this study is that Epo resistance associated with RAS
      blockade (RASB) is specific to men and related to drug-induced lowering of
      circulating testosterone. METHODS: Men and women undergoing chronic haemodialysis
      were divided into groups according to whether or not they were receiving RASB.
      Serum was collected pre-dialysis for determination of free testosterone levels by
      enzyme immunoassay. Routine laboratory data and Epo doses were collated and
      analysed for the 3 month period prior to the measurement of the hormone level.
      RESULTS: Control women required more Epo than control men (P=0.002), but the Epo
      doses between men and women with RASB were similar. Men with RASB required more
      Epo than control men (P=0.002), but RASB had no effect on Epo requirements in
      women. There was a significant relationship between age and testosterone levels
      in control men (P=0.01) that was not present in men taking RASB. RASB was
      associated with lower levels of serum testosterone in men <60 years old (P=0.02),
      but had no effect on serum testosterone levels in older men or women. Multiple
      regression analysis demonstrated that serum testosterone negatively correlated
      with Epo dose (P=0.045) when all groups of patients were considered together.
      CONCLUSIONS: These data suggest that androgens may participate in Epo resistance
      associated with RASB in patients on haemodialysis, and that the effect is related
      to both gender and age.

PMID- 15735243
TI  - Effective therapeutic use of rituximab in refractory Wegener's granulomatosis.

PMID- 15735245
TI  - Invasive apergillosis with myocardial involvement after kidney transplantation.

PMID- 15735244
TI  - Recovery from anti-recombinant-human-erythropoietin associated pure red cell
      aplasia in end-stage renal disease patients after renal transplantation.

PMID- 15735246
TI  - Desquamative interstitial pneumonia associated with concurrent cytomegalovirus
      and Aspergillus pneumonia in a renal transplant recipient.

PMID- 15735247
TI  - Resolution of thrombotic microangiopathy following renal transplant.

PMID- 15735248
TI  - Very low calorie diets and hypokalaemia: the importance of ammonium excretion.

PMID- 15735249
TI  - Virchow-Troisier's node in a haemodialysed patient: it is not always cancer.

PMID- 15735250
TI  - Biliary casts in the kidney tubule.

PMID- 15735251
TI  - Emphysematous cystitis.

PMID- 15735252
TI  - Jaccoud's nephritis.

PMID- 15735253
TI  - High-protein diets are not hazardous for the healthy kidneys.

PMID- 15735254
TI  - Sevelamer and pharmacokinetics of cyclosporin A after kidney transplantation.

PMID- 15735255
TI  - New-onset type II diabetes mellitus, hyperosmolar non-ketotic coma,
      rhabdomyolysis and acute renal failure in a patient treated with sulpiride.

PMID- 15735256
TI  - Blade Runner, blackout and haemofiltration: dialysis in times of catastrophe.

PMID- 15735257
TI  - Interaction between voriconazole and tacrolimus in a kidney-transplanted patient.

PMID- 15735258
TI  - Cystic fibrosis pulmonary disease is not a contra-indication to live-related
      renal transplantation.

PMID- 15735260
TI  - Should ultrasound guidance be used for central venous catheterisation in the
      emergency department?
AB  - In September 2002, the National Institute of Clinical Excellence (NICE) issued
      guidelines for England and Wales suggesting that ultrasound guidance should be
      used for all electives, and should be considered for most emergency, central
      venous catheterisations.1 These guidelines propose a major change of practice for
      most clinicians practising in UK Emergency Departments. There are also resource
      and training implications. In this paper we systematically review the literature
      to establish what evidence exists for the routine use of ultrasound guidance in
      the placement of central venous catheters in adult patients attending the
      Emergency Department, and provide an overview of the practical elements of this
      procedure.

PMID- 15735262
TI  - Rationing in the emergency department: the good, the bad, and the unacceptable.
AB  - OBJECTIVES: Waiting times in emergency departments (EDs) are an important
      government priority. Although substantial efforts are currently being made to
      reduce waiting times, little attention has been paid to the patients' view. We
      used qualitative methods to explore patients' perspectives on waiting times and
      other approaches to rationing and prioritisation. METHODS: Face to face, in
      depth, qualitative interviews (n = 11) explored how patients valued waiting times
      for non-urgent ED care. The framework approach (identifying a thematic framework
      through repeated re-reading) was used to analyse transcripts. RESULTS:
      Interviewees found some forms of rationing and prioritisation acceptable. They
      expected rationing by delay, but required explanations or information on the
      reason for their wait. They valued prioritisation by triage (rationing by
      selection) and thought that this role could be expanded for the re-direction of
      non-urgent patients elsewhere (rationing by deflection). Interviewees were mainly
      unwilling or unable to engage in prioritisation of different types of patients,
      openly prioritising only those with obvious clinical need, and children. However,
      some interviewees were willing to ration implicitly, labelling some attenders as
      inappropriate, such as those causing a nuisance. Others felt it was unacceptable
      to blame "inappropriate" attenders, as their attendance may relate to lack of
      information or awareness of service use. Explicit rationing between services was
      not acceptable, although some believed there were more important priorities for
      NHS resources than ED waiting times. Interviewees disagreed with the hypothetical
      notion of paying to be seen more quickly in the ED (rationing by charging).
      CONCLUSIONS: Interviewees expected to wait and accepted the need for
      prioritisation, although they were reluctant to engage in judgements regarding
      prioritisation. They supported the re-direction of patients with certain non
      urgent complaints. However, they perceived a need for more explanation and
      information about their wait, the system, and alternative services.

PMID- 15735261
TI  - Urban legend versus rural reality: patients' experience of attendance at accident
      and emergency departments in west Wales.
AB  - OBJECTIVES: To investigate why and how patients decide to attend accident and
      emergency (A&E) departments, and to assess their satisfaction with the
      experience, in a predominantly rural west Wales population. METHODS: This was a
      semi-structured follow up telephone interview of patients who walked in to A&E in
      one of four general hospitals in west Wales and were triaged as Manchester Triage
      score 4 or 5. Patients were recruited by nurses during the period July-November
      2002. The study sample consisted of 176 male and 145 female patients, mean (SD)
      age 36.6 (20.0) years. The main outcome measure was a quantitative and
      qualitative description of the recalled experiences of A&E attenders, the
      circumstances of their attendance, and their satisfaction with the experience.
      RESULTS: Of the study sample, 78% attended with injury or illnesses of recent
      origin, and 50% with actual or presumed musculoskeletal injury, 73% of which were
      sustained within 10 miles of home. Travel to hospital was by private transport
      for 86%, average distance 7.4 miles. The majority (90%) were registered with a
      local GP, but 32% felt A&E was the obvious choice, and a further 44% considered
      their GP inaccessible to their needs. Patients' reasons for seeking health care
      at A&E were similar to those described in an English urban study. Waiting times
      were rarely excessive; 80% left within 2 hours, and patient satisfaction was
      generally high. Among the 87 patients (27%) who reported a less satisfactory
      experience, 48 (55%) of these complained of dismissive attitudes of doctors.
      CONCLUSIONS: Anecdotal accounts of abuse of A&E services and unreasonable patient
      expectations gain the status of "urban legends" within the medical profession.
      Among the predominantly settled rural population in west Wales, there is little
      evidence of unreasonable patient expectations, and most patients report high
      satisfaction levels. Patients' bad experiences most frequently arise from a
      dismissive attitude on the part of medical staff. These attitudes are often
      consequent on an A&E culture that views some patients' attendances as less
      appropriate than others.

PMID- 15735263
TI  - Capillary versus venous bedside blood glucose estimations.
AB  - OBJECTIVES: To determine the mean difference and correlation between capillary
      and venous bedside glucose estimation in comparison to laboratory blood glucose
      analysis in emergency department (ED) patients. METHODS: Blood glucose levels
      were synchronously analysed using a bedside blood glucometer on capillary and
      venous derived samples from consenting ED patients aged >12 years. The venous
      sample was sent for comparative testing using a laboratory based multichannel
      analyser. Mean difference and correlation coefficients were determined. RESULTS:
      A total of 20 subjects (aged 13-88 years) were enrolled, with 100% data capture.
      The mean laboratory glucose was 7.075 mmol/l. The mean capillary blood glucose
      was 7.66 mmol/l (mean difference compared with mean laboratory glucose 0.58
      mmol/l; 95% confidence interval 0.3 to 0.9). The mean venous derived blood
      glucometer glucose was 7.99 mmol/l (mean difference compared with mean laboratory
      glucose 0.91 mmol/l; 95% CI 0.6 to 1.2). The correlation coefficient for the
      laboratory blood glucose versus the capillary blood glucometer glucose was 0.97
      mmol/l (p<0.001). The correlation coefficient for the laboratory blood glucose
      and the venous blood glucometer glucose was 0.96 (p<0.001). Variation occurred
      between the glucometer and the laboratory blood glucose results. CONCLUSIONS:
      There is a small but significant difference in the blood glucose results analysed
      on a bedside glucometer when the samples are taken from capillary or venous
      sources. Although good correlation is the norm between venous and capillary
      derived samples, caution must be exercised in accepting the results as equivalent
      or using either as substitutes for a laboratory blood glucose result.

PMID- 15735264
TI  - Simple nomograms to calculate sample size in diagnostic studies.
AB  - OBJECTIVES: To produce an easily understood and accessible tool for use by
      researchers in diagnostic studies. Diagnostic studies should have sample size
      calculations performed, but in practice, they are performed infrequently. This
      may be due to a reluctance on the part of researchers to use mathematical
      formulae. METHODS: Using a spreadsheet, we derived nomograms for calculating the
      number of patients required to determine the precision of a test's sensitivity or
      specificity. RESULTS: The nomograms could be easily used to determine the
      sensitivity and specificity of a test. CONCLUSIONS: In addition to being easy to
      use, the nomogram allows deduction of a missing parameter (number of patients,
      confidence intervals, prevalence, or sensitivity/specificity) if the other three
      are known. The nomogram can also be used retrospectively by the reader of
      published research as a rough estimating tool for sample size calculations.

PMID- 15735265
TI  - Rewarming of healthy volunteers after induced mild hypothermia: a healthy
      volunteer study.
AB  - OBJECTIVES: The study compares the efficacy of two active and one passive warming
      interventions in healthy volunteers with induced mild hypothermia. METHODS: Eight
      volunteers were studied in a random order crossover design. Each volunteer was
      studied during re-warming from a core temperature of 35 degrees C with each of: a
      radiant warmer (Fisher & Paykel); a forced air warmer (Augustine Medical), and a
      polyester filled blanket, to re-warm. RESULTS: No significant differences in re
      warming rates were observed between the three warming devices. It was found that
      the subject's endogenous heat production was the major contributor to the re
      warming of these volunteers. Metabolic rates of over 350 W were seen during the
      study. CONCLUSIONS: For patients with mild hypothermia and in whom shivering is
      not contraindicated our data would indicate that the rate of re-warming would be
      little different whether a blanket or one of the two active devices were used. In
      the field, this may provide the caregiver a useful choice.

PMID- 15735267
TI  - A users guide for reducing the pain of local anaesthetic administration.
AB  - Local anaesthetics (LAs) are used by medical practitioners in a number of
      clinical settings. The choice of agent and mode of administration is influenced
      by their experience, speciality and knowledge of the evidence base. Patients
      often express concern about the discomfort experienced during injection. Although
      short lived, the pain of LA administration in some patients is severe enough for
      them to decline future surgery. Methods to minimise the pain of LA administration
      relate to (1) the patient, (2) the LA, and (3) the injection technique (table 1).
      This article aims to provide a practical guide to doctors of all specialities who
      use LAs.

PMID- 15735266
TI  - Predictors of multi-organ dysfunction in heatstroke.
AB  - BACKGROUND: Heatstroke is a medical emergency that results from failure of
      thermoregulatory mechanism coupled with an exaggerated acute phase response,
      causing an elevation in core body temperature that rises above 40 degrees C,
      producing multi-organ dysfunction. It carries a high mortality rate, and in
      survivors, a risk of permanent neurological damage. OBJECTIVE: To investigate
      predictors of multiple organ dysfunction syndrome in patients presenting with
      heatstroke. METHODS: We investigated 28 patients admitted to a hospital in
      southern India during the period January 1998 to December 2001. Using a standard
      form, we collected data on the patients' characteristics, laboratory data, and
      outcome, and compared those with multiple organ dysfunction with those without
      such dysfunction. RESULTS: We found that more than three quarters of the studied
      patients developed multiple organ dysfunction, with the most common dysfunction
      being respiratory failure. Among the selected predictors, metabolic acidosis 14
      of 16 patients, 87.5%; p = 0.011, elevated CPK 17 of 19 patients, 89.5%; p =
      0.005, and liver enzymes elevated more than twice the normal (11 of 18 patients,
      61%; p = 0.02) had the highest correlation with dysfunction of two or more
      organs. CONCLUSIONS: The high mortality observed in heatstroke is secondary to
      multi-organ dysfunction, and among the various parameters assessed, high levels
      of CPK (>1000 IU/l), metabolic acidosis, and elevated liver enzymes are
      predictive. Aggressive measures to lower the body temperature with other
      supportive therapy could substantially reduce the mortality.

PMID- 15735268
TI  - Best evidence topic report. Role of flexion/extension radiography in paediatric
      neck injuries.
AB  - A short cut review was carried out to establish the potential utility of
      flexion/extension views of the cervical spine in children with neck injuries.
      Using the reported search, 51 papers were found, of which three presented the
      best evidence to answer the clinical question. The author, date, and country of
      publication, patient group studied, study type, relevant outcomes, results, and
      study weaknesses of these best papers are tabulated. A clinical bottom line is
      stated.

PMID- 15735270
TI  - Best evidence topic report. Use of troponin for the diagnosis of myocardial
      contusion after blunt chest trauma.
AB  - A short cut review was carried out to establish the utility of troponin levels in
      diagnosing myocardial contusion following blunt chest trauma. Using the reported
      search, 75 papers were found, of which six presented the best evidence to answer
      the clinical question. The author, date, and country of publication, patient
      group studied, study type, relevant outcomes, results, and study weaknesses of
      these best papers are tabulated. A clinical bottom line is stated.

PMID- 15735271
TI  - Best evidence topic report. Scorpion envenomation: does antivenom reduce serum
      venom concentrations?
AB  - A short cut review was carried out to determine if anitvenom reduces serum venom
      concentrations. Using the reported search, 69 papers were found, of which four
      presented the best evidence to answer the clinical question. The author, date,
      and country of publication, patient group studied, study type, relevant outcomes,
      results, and study weaknesses of these best papers are tabulated. A clinical
      bottom line is stated.

PMID- 15735272
TI  - Best evidence topic report. Scorpion envenomation: does administration of
      antivenom alter outcome?
AB  - A short cut review was carried out to establish the clinical utility of antivenom
      in scorpion poisoning. Using the reported search, 69 papers were found, of which
      four presented the best evidence to answer the clinical question. The author,
      date, and country of publication, patient group studied, study type, relevant
      outcomes, results, and study weaknesses of these best papers are tabulated. A
      clinical bottom line is stated.

PMID- 15735273
TI  - SOCRATES 5 (Synopsis of Cochrane Reviews applicable to Emergency Services).

PMID- 15735274
TI  - 10 Nausea, vomiting and fever.

PMID- 15735275
TI  - Pre-hospital management of burns by the UK fire service.
AB  - OBJECTIVE: To determine the current policies and practice of UK fire services for
      the management of burns patients. METHODS: Structured telephone questionnaire
      covering formal policies including patient assessment, oxygen and entonox use,
      burn assessment and treatment, and paediatric patients and training. RESULTS: The
      questionnaire was completed by 74% of the UK Fire Services (n = 46); only 14 had
      a specific written policy for the management of burns. Most services use "ABC" or
      "First Aid at Work" principles, although five have no formal guidelines for
      patient assessment. Oxygen is given by 44 services, all services cool burns with
      water and/or dressings, and 31 assess burn size. The same protocols are used for
      both adults and children by 29 brigades, while two brigades use lower oxygen
      concentrations for children. Only three brigades receive joint training from the
      fire and ambulance services. CONCLUSIONS: UK firefighters are in an ideal
      position to provide early assessment and treatment of burns, but there is
      currently a wide variation in the fire services' management of these patients.
      There is a need for clear evidence based national guidelines for all pre-hospital
      providers to standardise patient care for burns. A suggested protocol is included
      in this report.

PMID- 15735276
TI  - Limited benefits of ambulance telemetry in delivering early thrombolysis: a
      randomised controlled trial.
AB  - OBJECTIVES: To evaluate the potential of a continuous telemetry system linking
      rural ambulances to a coronary care unit to reduce call to thrombolysis times.
      METHODS: This prospective randomised controlled trial recruited patients using
      the 999 ambulance service in a rural area of the UK with signs or symptoms of
      coronary heart disease. Subjects were assigned to receive either standard
      paramedic treatment or transmission of 12 lead ECG, blood pressure, pulse
      oximetry, and relevant medical history to a general hospital coronary care unit.
      Cardiology senior house officers then determined each patient's suitability for
      pre-hospital thrombolysis time, and transmitted this decision back to the
      ambulance. This was documented as the potential thrombolysis, although no
      thrombolytic agents were administered by paramedics. The between groups
      difference in time to potential thrombolysis (intervention group) and actual
      thrombolysis (controls) was compared. The proportion of intervention group
      subjects ultimately receiving thrombolysis in hospital was compared with that
      recommended for pre-hospital thrombolysis. RESULTS: The potential reduction in
      call to treatment time for telemetry patients recommended for pre-hospital
      thrombolysis was 55 minutes (p = 0.022). Following hospital admission,21/213 of
      the telemetry patients were thrombolysed (10%, 95% confidence interval (CI) 6% to
      15%). Of these patients, 3/21 received a recommendation for thrombolysis in the
      ambulance (14%, 95% CI 3.1% to 36.3%). The sensitivity and specificity of the
      telemetry system in detecting patients requiring thrombolysis was 13.6 and 99.5%
      respectively. Errors were made in the pre-hospital treatment recommendations for
      two patients. CONCLUSIONS: Continuous telemetry systems may significantly reduce
      call to treatment times for patients recommended for pre-hospital thrombolysis in
      a rural setting. However, this benefit must be balanced against the very small
      proportion of eligible patients identified as suitable for pre-hospital
      thrombolysis. This limitation may be due to communications problems, the criteria
      used to identify eligible patients, or the seniority of physicians tasked with
      making treatment decisions.

PMID- 15735277
TI  - Have the implementation of a new specialised emergency medical service influenced
      the pattern of general practitioners involvement in pre-hospital medical
      emergencies? A study of geographic variations in alerting, dispatch, and
      response.
AB  - OBJECTIVES: Emergency medical service systems in Norway are based on equity and
      equality. A toll free number (113) and criteria based dispatch are crucial
      components. The establishment of an emergency medical system (EMS) manned by an
      air and ground emergency physician (EP) has challenged the role of the general
      practitioner (GP) in emergency medical care. We investigated whether there were
      any geographical differences in the use of 113, alerts to GPs by the emergency
      medical dispatch centres (EMDCs), and of the presence of GPs on scene in medical
      emergencies leading to a turnout of the EP manned EMS. METHODS: This was a
      prospective, observational cohort study of 385,000 inhabitants covered by the two
      EMDCs of Rogaland county, Norway, including 1035 on scene missions of the EP
      manned EMS during the period 1998-99. RESULTS: The proportion of emergency calls
      routed through 113 was significantly lower, the proportion of alerts to GPs
      significantly higher, and the proportions of GPs on scene significantly higher in
      rural than urban areas. CONCLUSION: We found geographical differences in the
      involvement of GPs in pre-hospital emergency medical situations, probably caused
      by a specialised emergency medical service system including an EMDC and an air
      and ground EP manned EMS. There were geographical differences in public use of
      the toll free 113, and alerts to GPs by the EMDCs, which is likely to result from
      geographical conditions and proximity to medical resources. Future organisation
      of the EMS has to reflect this to prevent unplanned and unwanted autonomously
      emerging EMS systems.

PMID- 15735278
TI  - Tension viscerothorax: an important differential for tension pneumothorax.

PMID- 15735279
TI  - Irreducible volar dislocations of the proximal interphalangeal joint.

PMID- 15735280
TI  - Low cost, high risk: accidental nutmeg intoxication.
AB  - Nutmeg poisoning is rare but probably underreported and should be considered in
      recreational substance users with acute psychotic symptoms as well as central
      nervous system neuromodulatory signs that may mimic in part an anticholinergic
      hyperstimulation.

PMID- 15735281
TI  - Atlas: standard diagnostic tests for an unusual fracture.
AB  - The case is reported of an unusual atlas fracture with no reports of such an
      injury in the literature. The diagnosis of this injury emphasises the importance
      of simple clinical decision instruments, and systematic interpretation of
      investigations.

PMID- 15735282
TI  - Descending necrotising mediastinitis: a report of misdiagnosis as thoracic aortic
      dissection.
AB  - Descending necrotising mediastinitis is an uncommon disease in the emergency
      department. Early recognition is important for a good prognosis for this fatal
      condition. This report describes a case of a healthy 79 year old woman who was
      seen in the urgent care centre with the initial presentation of chest pain.
      Misdiagnosis was made because of the mis-reading of a flap-like artefact over the
      ascending aorta and difficulty interpreting subtle change of mediastinal soft
      tissue infiltration. The patient was then treated as dissecting aneurysm over
      ascending aorta until her condition deteriorated. Although aggressive treatment
      comprising thoracotomy, cervical incision and drainage, and antibiotics were
      begun, the response was poor. Emergency physicians should be familiar with this
      rare but highly lethal disease. Correlation should be made in a patient
      complaining about chest pain, especially combined with fever, sore throat,
      dysphagia, or neck swelling.

PMID- 15735283
TI  - A case of thoracic aortic dissection presenting as lateral pleuritic chest pain.
AB  - An unusual presentation of thoracic aortic dissection in a 73 year old man is
      described. He was admitted to hospital with severe left sided pleuritic chest
      pain. Examination on admission was normal apart from minor tenderness on
      palpation of the left lower chest wall. Chest x ray showed cardiomegaly with
      right lung shadowing, and ventilation/perfusion scan was negative. Spiral
      computed tomography done on the fourth day showed a false lumen on the ascending
      aorta. He underwent surgery but deteriorated postoperatively because of
      intrathoracic bleeding and developed cardiac tamponade from which resuscitation
      was not possible.

PMID- 15735284
TI  - Pneumomediastinum secondary to an apparently trivial stab wound to the neck: the
      value of the Hamman's sign and thorough radiological investigation.
AB  - Perforation of the pharynx and upper oesophagus after stab wounds to the neck is
      easily overlooked because of the relative lack of symptoms. A case is reported in
      which pneumomediastinum occurred after an apparently trivial neck wound.

PMID- 15735285
TI  - Missed clavicular fracture; inadequate radiograph or occult fracture?

PMID- 15735286
TI  - "See and treat" is great--if you're a general practitioner.

PMID- 15735287
TI  - Tobacco in sport: an endless addiction?

PMID- 15735288
TI  - Austria: small but deadly.

PMID- 15735289
TI  - China: tobacco museum's "smoky" health information.

PMID- 15735290
TI  - Kenya: beach party "helps" tobacco bill.

PMID- 15735291
TI  - USA: the smokin' Marlboro man of Fallujah.

PMID- 15735293
TI  - Leaders and elites: portrayals of smoking in popular films.
AB  - OBJECTIVE: To study frequency and traits of characters that smoke in films and to
      document on-screen consequences of tobacco use. DESIGN: This study conducted a
      content analysis of the top 100 grossing films in 2002, with a total global gross
      of 12.4 billion US dollars. OUTCOME MEASURES: Three outcome measures were
      frequency of smoking incidents, traits of characters who smoke, and consequences
      of tobacco use. RESULTS: 6% of characters smoked in 453 incidents, including 3%
      of children. In 92% of incidences, smoking had no consequences. The most frequent
      consequence was a verbal reprimand. Although tobacco is a leading cause of
      preventable deaths globally, only 0.4% of tobacco incidences resulted in death.
      No deaths were caused by disease. Characters who smoked tended to be major
      characters playing leadership roles. They tended to be from privileged elites:
      male, white, and mature. CONCLUSIONS: Films portray characters that smoke as
      leaders from privileged elites, making smoking more attractive to audience
      members. Because 99.6% of characters suffer no life threatening consequences from
      smoking on screen, smokers seem invincible, belying tobacco's role as a leading
      cause of preventable deaths.

PMID- 15735294
TI  - Smoke-free law did not affect revenue from gaming in Delaware.
AB  - OBJECTIVE: To determine the effect of the Delaware smoke-free law on gaming
      revenue. METHODS: Linear regression of gaming revenue and average revenue per
      machine on a public policy variable, time, while controlling for economic
      activity and seasonal effects. RESULTS: The linear regression showed that the
      smoke-free law was associated with no effect on total revenue or average revenue
      per machine. CONCLUSION: Smoke-free laws are associated with no change in gaming
      revenue.

PMID- 15735295
TI  - Exploring the impact of foreign direct investment on tobacco consumption in the
      former Soviet Union.
AB  - BACKGROUND: Tobacco is the single largest cause of morbidity and mortality in the
      developed world; in the former socialist bloc tobacco kills twice as many men as
      in the west. Although evidence shows that liberalisation of the cigarette trade
      through the elimination of import barriers leads to significant increases in
      consumption, far less is known about the impact of foreign direct investment on
      cigarette consumption. This paper seeks to explore the impact that the
      substantial transnational tobacco company investments have had on patterns of
      tobacco trade and consumption in the former Soviet Union. DESIGN: Routine data
      were used to explore trends in cigarette trade and consumption in the 15
      countries of the former Soviet Union from the 1960s to the present day.
      Comparisons were made between trends in countries that have received substantial
      investment from the tobacco transnationals and countries that have not. RESULTS:
      Between 1991 and 2000 cigarette production increased by 96% in countries
      receiving industry investment and by 11% in countries that did not. Over the same
      period cigarette consumption increased by 40%; the increase was concentrated in
      countries receiving investments. Despite these investments, cigarette imports
      still outweigh exports and no trade surplus has yet to result. CONCLUSIONS: The
      findings suggest that liberalisation of inward investment has a significant and
      positive impact on cigarette consumption and that without appropriate safeguards,
      market liberalisation may have long term negative impacts on health. Specific
      trade rules are needed to govern trade and investment in this uniquely harmful
      product. Implementation of effective tobacco control policies should precede
      tobacco industry privatisation. International financial organisations pressing
      for privatisation should ensure this occurs.

PMID- 15735296
TI  - Tobacco control implications of the first European product liability suit.
AB  - OBJECTIVE: To examine tobacco control implication of the first European product
      liability suit in Finland. METHODS: Systematic search of internal tobacco
      industry documents available on the internet and at the British American Tobacco
      Guildford Depository. RESULTS: Despite legal loss, the litigation contributed to
      subsequent tobacco control legislation in Finland. The proceedings revealed that
      the industry had concealed the health hazards of its products and, despite
      indisputable evidence, continued to deny them. The positions taken by the
      industry rocked its reliability as a social actor and thus weakened its chances
      of influencing tobacco policy. Despite fierce opposition from the tobacco
      industry, tobacco products were included in the product liability legislation,
      tobacco was entered on the Finnish list of carcinogens, and an extensive Tobacco
      Act was passed in Parliament. CONCLUSIONS: Tobacco litigation might not stand
      alone as a tool for public health policymaking but it may well stimulate national
      debate over the role of smoking in society and influence the policy agenda.

PMID- 15735297
TI  - Smokeless tobacco use among professional baseball players: survey results, 1998
      to 2003.
AB  - OBJECTIVE: The use of smokeless tobacco (ST) (snuff and chewing tobacco) has long
      been associated with baseball in the USA. This article reviews six years of
      survey data from major and minor league baseball players to evaluate trends in
      tobacco use and quitting patterns over time in order to gain insight into the
      effects of past interventions and to document continued intervention needs.
      METHOD: Surveys were distributed by athletic trainers to major and minor league
      professional baseball players during spring training session in the six years
      from 1998 to 2003. The surveys were anonymous and identified only by team, level
      of league, and other self reported demographic data. RESULTS: ST use among
      professional baseball players remains much higher than among young males in the
      general population, and use is most prevalent among white non-Hispanic players.
      There was a significant decrease in ST use among minor league players from 1998
      to 2003, with seven day self reported use declining from 31.7% in 1998 to 24.8%
      in 2003. No significant year to year changes were observed for major league
      players. Major league players' self reported past week use rates, estimated at
      35.9% in 1998 and at 36% in 2003, were consistently higher than those of minor
      league players. Self reported prevalence of past month cigarette and cigar
      smoking was much lower than ST use for both major and minor league players.
      CONCLUSIONS: Six years of survey data confirm a continuing high use of ST among
      professional baseball players. Results suggest that the effects of the broad
      spectrum ST control efforts launched over the past decade may have been stronger
      among minor than major league players. Stronger policy interventions at the major
      league level and multi-level efforts, including programmes to increase the use of
      effective quitting aids and assistance, at both levels of play are needed. Future
      research is needed to further clarify changes in ST practices among professional
      players and set policy intervention directions.

PMID- 15735298
TI  - Cost effectiveness of a community based research project to help women quit
      smoking.
AB  - OBJECTIVE: To estimate the cost effectiveness of a four year, multifaceted,
      community based research project shown previously to help women quit smoking.
      DESIGN: A quasi-experimental matched control design. SETTING: Two counties in
      Vermont and two in New Hampshire, USA. SUBJECTS: Women aged 18-64 years. METHODS:
      Costs were the grant related expenditures converted to 2002 US dollars. Survey
      results at the end of the intervention were used to estimate the numbers of never
      smokers, former smokers, light smokers, and heavy smokers in the intervention and
      comparison counties, and 1986 life tables for populations of US women categorised
      by smoking status to estimate the gain in life expectancy. MAIN OUTCOME MEASURES:
      Cost effectiveness ratios, as dollars per life-year saved, for the intervention
      only and for total grant costs (intervention, evaluation and indirect costs).
      RESULTS: The cost effectiveness ratio for the intervention, in 2002 US dollars
      per life-year saved, discounted at 3%, was 1156 dollars (90% confidence interval
      (CI) 567 dollars to infinity), and for the total grant, 4022 dollars (90% CI 1973
      dollars to infinity). When discounted at 5%, these ratios were 1922 dollars (90%
      CI 1024 dollars to 15,647 dollars), and 6683 dollars (90% CI 3555 dollars to
      54,422 dollars), respectively. CONCLUSION: The cost effectiveness ratios of this
      research project are economically attractive, and are comparable with other
      smoking cessation interventions for women. These observations should encourage
      further research and dissemination of community based interventions to reduce
      smoking.

PMID- 15735299
TI  - Strength of clean indoor air laws and smoking related outcomes in the USA.
AB  - OBJECTIVES: Environmental tobacco smoke (ETS) is often encountered in the
      workplace. There have been efforts to apply and enforce state laws limiting
      workplace smoking. There has been little study of the relative effectiveness of
      state and/or local laws in affecting both rates of workplace ETS exposure and
      adult smoking rates. This study investigates these hypotheses, as well as the
      effect of these laws on youth smoking. DESIGN: This is a secondary data analysis
      using sources including the Current Population Survey (CPS), Behavioral Risk
      Factor Surveillance System (BRFSS), Youth Risk Behavior Survey (YRBS), and the
      National Household Survey of Drug Abuse (NHSDA) between the years of 1996 and
      1999. Linear regression models were used to investigate the effect of a state's
      clean indoor air (CIA) law (using a measure of extensiveness) on the overall
      amount of people who reported working in a smoke-free environment, youth smoking
      rates and adult smoking rates. RESULTS: The extensiveness of a state's CIA law
      was found to be a reliable predictor of the percentage of indoor workers who
      report a smoke-free work environment and the rates of youth smoking. State CIA
      laws were not conclusively associated with adult smoking rates. CONCLUSIONS: The
      extensiveness of a state's CIA law is strongly associated with a higher
      percentage of indoor workers reporting a smoke-free work environment. This study
      did not reveal a similar association between local laws and smoke-free work
      environments. Youth smoking rates, shown to be related to state CIA laws, may be
      further affected with more stringent CIA policy.

PMID- 15735300
TI  - A prospective study of off-label use of, abuse of, and dependence on nicotine
      inhaler.
AB  - OBJECTIVE: To determine the incidence of off-label use of, abuse of, and
      dependence on prescription nicotine inhaler. DESIGN: Prospective telephone and
      internet interviews for six months. PARTICIPANTS: 535 new inhaler users. MAIN
      OUTCOME: Structured interview about off-label use (that is, use of inhaler for
      non-cessation reasons or concurrent use of inhaler and cigarettes) and Diagnostic
      and statistical manual, fourth edition (DSM-IV) and International classification
      of diseases, 10th edition (ICD-10) criteria for abuse and dependence RESULTS:
      Although many used inhaler and cigarettes concurrently at some time (43-55%), few
      used inhaler for non-cessation reasons (4-9%) and few persisted in off label use
      (8-16%; 95% confidence interval (CI) 5% to 19%). No participant met ICD-10
      criteria for harmful use/abuse (95% CI 0% to 3.3%). Eight subjects (1.4%)
      appeared to meet DSM-IV or ICD-10 criteria for dependence on inhaler, but none
      were found dependent in a clinical expert interview (95% CI 0% to 3.3%).
      CONCLUSIONS: Although transient concurrent use of inhaler and cigarettes often
      occurs, use for non-cessation reasons, abuse and dependence are rare.

PMID- 15735301
TI  - Smokers' unrealistic optimism about their risk.
AB  - OBJECTIVE: Past studies have produced ambiguous or inconsistent results when
      testing whether smokers actually underestimate their own risks of experiencing
      tobacco related illness. Whereas smokers claim that they are less at risk than
      the average smoker on self administered questionnaires, this unrealistic optimism
      has not been found in telephone or face-to-face interviews. We avoided the
      measurement problems of past studies and examined responses to a number of new
      questions to assess different aspects of smokers' perceptions. METHODOLOGY: A US
      national telephone survey (n = 6369; 1245 current smokers) posed a variety of
      questions designed to examine beliefs about the risks of smoking. For key
      questions, separate samples of smokers were asked either about their own risk or
      about the risk of the average smoker. RESULTS: Smokers underestimated their
      relative risk compared to non-smokers and, contrary to previous interview
      surveys, believed they have a lower risk of developing lung cancer than the
      average smoker. Furthermore, their perceived risk of lung cancer and of cancer in
      general barely increases with the number of cigarettes smoked per day, and their
      estimates of their risk of cancer are actually slightly lower than their
      estimates of their risk of lung cancer. Substantial proportions of smokers and
      former smokers agree with several myths, more than half agreeing that exercise
      undoes most smoking effects. CONCLUSION: Smokers underestimate their risk of lung
      cancer both relative to other smokers and to non-smokers and demonstrate other
      misunderstandings of smoking risks. Smoking cannot be interpreted as a choice
      made in the presence of full information about the potential harm.

PMID- 15735303
TI  - An extremely compensatible cigarette by design: documentary evidence on industry
      awareness and reactions to the Barclay filter design cheating the tar testing
      system.
AB  - BACKGROUND: The Barclay cigarette (Brown & Williamson) was introduced in 1980 in
      the USA in the most expensive launch in history. In the USA and around the world,
      Barclay was later determined to have a grooved filter design that was compromised
      by human smokers in the normal act of smoking, but that was measured as ultra-low
      tar using the standard tar testing protocol. OBJECTIVES: To evaluate whether
      Brown & Williamson knew of the compensatability of Barclay during the design
      process and before it was released; to evaluate initial responses of competing
      tobacco companies to Barclay, before complaints were made to the Federal Trade
      Commission in 1981. METHODS: Internet databases of industry documents (Tobacco
      Documents Online, Legacy Tobacco Documents Library, Brown & Williamson Litigation
      discovery website, Guildford and major company websites) were searched using key
      words, key dates, and targeted searches. Documents related specifically to the
      development, evaluation and release of the Barclay cigarette and related to the
      responses by competing tobacco companies were examined. RESULTS: Documents
      indicate the manufacturer was aware of Barclay design problems and was planning,
      before release, to respond to criticism. Competing companies quickly detected the
      filter groove stratagem and considered developing their own similar filter, but
      eventually backed off. CONCLUSION: The design problems with Barclay were readily
      understood by cigarette manufacturers, including the maker of Barclay, before
      official governmental evaluations occurred. Testing involving measured exposures
      to human smokers may in the end be crucial to identifying problems with novel
      cigarette designs.

PMID- 15735304
TI  - Smoking scenes in Japanese comics: a preliminary study.

PMID- 15735302
TI  - Environmental tobacco smoke exposure in public places of European cities.
AB  - BACKGROUND: Exposure to environmental tobacco smoke (ETS) has important public
      health implications. The results of the first European multi-centre study that
      measured ETS exposure in a range of public places (transport, educational
      settings, and leisure facilities such as bars and restaurants) are presented.
      METHOD: Nicotine vapour phase was measured using ETS passive samplers containing
      a filter treated with sodium bisulfate. RESULTS: Bars and discos are the places
      with the highest concentrations of nicotine from ETS, median ranging from 19 to
      122 microg/m(3). Restaurants had the next highest values. Concentrations of
      nicotine generally range from 0.1-5 microg/m(3) in airports, and from 0.5-10
      microg/m(3) in train stations. Nicotine was also found in schools and
      universities, yet schools tended to have the lowest concentrations compared to
      all the other public places sampled. In hospitals levels were generally below 5
      microg/m(3). CONCLUSIONS: Although there is some variability between cities, this
      study shows that tobacco smoke is present in most of the studied public places.
      The study also showed that in areas where smoking is prohibited, concentrations
      of nicotine are lower than in areas where smoking is allowed but they are not
      zero. The results of this study indicate that policies should be implemented that
      would effectively reduce levels of tobacco smoke in public areas.

PMID- 15735305
TI  - Synthesis of the blood circulating C-terminal fragment of insulin-like growth
      factor (IGF)-binding protein-4 in its native conformation. Crystallization,
      heparin and IGF binding, and osteogenic activity.
AB  - Insulin-like growth factor-binding proteins play a critical role in a wide
      variety of important physiological processes. It has been demonstrated that both
      an N-terminal and a C-terminal fragment of insulin-like growth factor-binding
      protein-4 exist and accumulate in the circulatory system, these fragments
      accounting for virtually the whole amino acid sequence of the protein. The
      circulating C-terminal fragment establishes three disulfide bridges, and the
      binding pattern of these has recently been defined. Here we show that the
      monodimensional 1H NMR spectrum of the C-terminal fragment is typical of a
      protein with a relatively close packed tertiary structure. This fragment can be
      produced in its native conformation in Escherichia coli, without the requirement
      of further refolding procedures, when synthesis is coupled to its secretion from
      the cell. The recombinant protein crystallizes with the unit cell parameters of a
      hexagonal system. Furthermore, it binds strongly to heparin, acquiring a well
      defined oligomeric structure that interacts with insulin-like growth factors, and
      promotes bone formation in cultures of murine calvariae.

PMID- 15735306
TI  - Regulation of neuroprotective activity of myocyte-enhancer factor 2 by cAMP
      protein kinase A signaling pathway in neuronal survival.
AB  - The transcription factor myocyte-enhancer factor 2 (MEF2) has been shown to be
      required for the survival of different types of neurons. However, the death- or
      survival-inducing second messenger pathways that regulate MEF2 activity remain to
      be fully elucidated. Membrane depolarization by KCl induces neuronal survival
      that is dependent upon MEF2-mediated gene transactivation. Here we report that
      membrane depolarizationinduced activation of MEF2 requires the cAMP-protein
      kinase A (PKA) pathway. Inhibition of the activity of cAMP-PKA pathway attenuates
      membrane depolarization-induced activation of MEF2 activity and neuronal
      survival, whereas enhancing the activity of this pathway prevents KCl withdrawal
      induced inhibition of MEF2 and neuronal apoptosis. Moreover, PKA directly
      phosphorylates MEF2 at Thr-20 in vitro to increase MEF2 DNA binding activity. A
      mutation of Thr-20 to Ala renders MEF2 resistant to PKA phosphorylation in vitro
      and reduces its DNA binding activity. Transfection of this T20A mutant blocks
      survival and induces apoptosis in cultured cortical and cerebellar granule
      neurons. This study identifies the transcription factor MEF2 as a target of cAMP
      PKA pathway and demonstrates that PKA phosphorylation of MEF2 is a key step in
      modulating its DNA binding activity and ability to promote neuronal survival.

PMID- 15735307
TI  - Structural basis for the function of stringent starvation protein a as a
      transcription factor.
AB  - Stringent starvation protein A (SspA) of Escherichia coli is an RNA polymerase
      associated transcriptional activator for the lytic development of phage P1 and is
      essential for stationary phase-induced acid tolerance of E. coli. We report the
      crystal structure of Yersinia pestis SspA, which is 83% identical to E. coli SspA
      in amino acid sequence and is functionally complementary in supporting the lytic
      growth of phage P1 and acid resistance of an E. coli sspA mutant. The structure
      reveals that SspA assumes the characteristic fold of glutathione S-transferase
      (GST). However, SspA lacks GST activity and does not bind glutathione. Three
      regions of SspA are flexible, the N and C termini and the alpha2-helix. The
      structure also reveals a conserved surface-exposed pocket composed of residues
      from a loop between helices alpha3 and alpha4. The functional roles of these
      structural features were investigated by assessing the ability of deletion and
      site-directed mutants to confer acid resistance of E. coli and to activate
      transcription from a phage P1 late promoter, thereby supporting the lytic growth
      of phage P1. The results indicate that the flexible regions are not critical for
      SspA function, whereas the surface pocket is important for both transcriptional
      activation of the phage P1 late promoter and acid resistance of E. coli. The
      size, shape, and property of the pocket suggest that it mediates protein-protein
      interactions. SspA orthologs from Y. pestis, Vibrio cholerae, and Pseudomonas
      aeruginosa are all functional in acid resistance of E. coli, whereas only Y.
      pestis SspA supports phage P1 growth.

PMID- 15735309
TI  - Energetics of structural transitions of the addiction antitoxin MazE: is a
      programmed bacterial cell death dependent on the intrinsically flexible nature of
      the antitoxins?
AB  - The Escherichia coli mazEF addiction module plays a crucial role in the cell
      death program that is triggered under various stress conditions. It codes for the
      toxin MazF and the antitoxin MazE, which interferes with the lethal action of the
      toxin. To better understand the role of various conformations of MazE in
      bacterial life, its order-disorder transitions were monitored by differential
      scanning calorimetry, spectropolarimetry, and fluorimetry. The changes in
      spectral and thermodynamic properties accompanying MazE dimer denaturation can be
      described in terms of a compensating reversible process of the partial folding of
      the unstructured C-terminal half (high mean net charge, low mean hydrophobicity)
      and monomerization coupled with the partial unfolding of the structured N
      terminal half (low mean net charge, high mean hydrophobicity). At pH<or=4.5 and
      T<50 degrees C, the unstructured polypeptide chains of the MazE dimer fold into
      (pre)molten globule-like conformations that thermally stabilize the dimeric form
      of the protein. The simulation based on the thermodynamic and structural
      information on various addiction modules suggests that both the conformational
      adaptability of the dimeric antitoxin form (binding to the toxins and DNA) and
      the reversible transformation to the more flexible monomeric form are essential
      for the regulation of bacterial cell life and death.

PMID- 15735310
TI  - Human immunodeficiency virus, hepatitis C and hepatitis B infections among blood
      donors in Germany 2000-2002: risk of virus transmission and the impact of nucleic
      acid amplification testing.
AB  - Blood and plasma donations in Germany are collected by several institutions,
      namely the German Red Cross, community and hospital-based blood services, private
      blood centres, commercial plasma donation sites and transfusion services of the
      army. All blood donation centres are required to report quarterly data on
      infection markers to the Robert Koch Institute, thus providing current and
      accurate epidemiological data. The prevalence and incidence of relevant viral
      infections are low in the blood donor population in Germany, with a decreasing
      trend for hepatitis C infections in new and repeat donors since 1997. The
      implementation of mandatory nucleic acid amplification technique (NAT) testing
      for hepatitis C virus (HCV) in 1999 has markedly improved transfusion safety. HIV
      NAT became mandatory in 2004 but was done voluntarily by the majority of the
      blood donation services before then. The potential benefit of hepatitis B virus
      (HBV) minipool NAT is not as clear because chronic HBV carriers with very low
      virus levels might donate unidentified. The residual risk of an infectious window
      period donation inadvertently entering the blood supply can be estimated using a
      mathematic model which multiplies the incidence rate by the number of days during
      which an infection may be present but not detectable, i.e. the length of the
      window period. The risk of an undetected infection without NAT testing was
      estimated to be 1 in 2,770,000 for HIV, 1 in 670,000 for HCV and 1 in 230,000 for
      HBV in 2001/2002. This contrasts with 1 in 5,540,000 for HIV, 1 in 4,400,000 for
      HCV and 1 in 620,000 for HBV with minipool NAT testing. This demonstrates that
      NAT testing can further reduce the already very small risk of infectious
      donations entering the blood supply.

PMID- 15735308
TI  - Crystal structure of a novel shikimate dehydrogenase from Haemophilus influenzae.
AB  - To date two classes of shikimate dehydrogenases have been identified and
      characterized, YdiB and AroE. YdiB is a bifunctional enzyme that catalyzes the
      reversible reductions of dehydroquinate to quinate and dehydroshikimate to
      shikimate in the presence of either NADH or NADPH. In contrast, AroE catalyzes
      the reversible reduction of dehydroshikimate to shikimate in the presence of
      NADPH. Here we report the crystal structure and biochemical characterization of
      HI0607, a novel class of shikimate dehydrogenase annotated as shikimate
      dehydrogenase-like. The kinetic properties of HI0607 are remarkably different
      from those of AroE and YdiB. In comparison with YdiB, HI0607 catalyzes the
      oxidation of shikimate but not quinate. The turnover rate for the oxidation of
      shikimate is approximately 1000-fold lower compared with that of AroE.
      Phylogenetic analysis reveals three independent clusters representing three
      classes of shikimate dehydrogenases, namely AroE, YdiB, and this newly
      characterized shikimate dehydrogenase-like protein. In addition, mutagenesis
      studies of two invariant residues, Asp-103 and Lys-67, indicate that they are
      important catalytic groups that may function as a catalytic pair in the shikimate
      dehydrogenase reaction. This is the first study that describes the crystal
      structure as well as mutagenesis and mechanistic analysis of this new class of
      shikimate dehydrogenase.

PMID- 15735311
TI  - Residual risk of transfusion-transmitted viral infections in Spain, 1997-2002,
      and impact of nucleic acid testing.
AB  - Estimates of the risk of bloodborne viral infections are essential for monitoring
      the safety of the blood supply and the impact of new screening tests. Incidence
      rates of seroconversion and the residual risk for HBV, HIV and HCV were
      calculated among Spanish repeat donors between 1997 and 1999 at 22 blood donation
      centres, and at 7 centres between 2000 and 2002. The residual risk per million
      donations was estimated to be 18.67 for HBV, 2.49 for HIV and 10.96 for HCV
      (between 1997 and 1999). For the 2000-2002 period, the residual risk per million
      donations was estimated to be 9.78 for HBV, 2.48 for HIV and 3.94 for HCV.
      Between 1999 and 2003, about 3.4 million donations were tested by NAT, mainly in
      pools of 44 donations, in 12 of the 22 Spanish blood donation centres
      participating in the study. Eight anti-HCV negative and HCV-RNA positive
      donations were found, which represent an approximate yield of 1/420,000, versus a
      projected yield of 1/240,000 obtained from 1995-1997 data. The residual risks of
      transfusion-transmitted viral infections in Spain were low, and with the
      implementation of NAT these risks are even lower.

PMID- 15735312
TI  - Estimates of the frequency of HBV, HCV, and HIV infectious donations entering the
      blood supply in the United Kingdom, 1996 to 2003.
AB  - Several new tests have been recently introduced by the United Kingdom Blood
      Services to improve safety. The frequency (or risk) of hepatitis B virus (HBV),
      hepatitis C virus (HCV) and HIV infectious donations entering the UK blood supply
      during 1996-2003 has been estimated. These years span the introduction of nucleic
      acid testing (NAT) for HCV, HIV combination antigen and antibody test and NAT for
      HIV. The frequency of an infectious donation entering the blood supply due to i)
      the window period, ii) assay failures and iii) human and technical errors in
      testing and processing, was estimated. The window period risk was estimated using
      the incidence of infection in donors and the length of the window period for
      tests in use, with an adjustment for atypical inter-donation intervals in
      seroconverting donors. The estimated frequency of infectious donations entering
      the blood supply during 1996-2003 was 1.66, 0.80 and 0.14 per million for HBV,
      HCV and HIV respectively. HCV NAT resulted in an over 95% fall in the risk of
      HCV. Current usage of HIV combined antibody-antigen tests and of HIV NAT reduced
      the estimated risk of HIV by 10%. Since 1996, the risk of transfusion-transmitted
      HBV, HCV and HIV infection in the UK has been lowered by several improvements to
      donation testing, although the absolute reduction in risk has been small.
      Vigilance for errors and the affects of donor selection may be as or more
      important than further reductions to window periods of tests for improving blood
      safety with respect to HBV, HCV and HIV.

PMID- 15735313
TI  - Trends in risk of transfusion-transmitted viral infections (HIV, HCV, HBV) in
      France between 1992 and 2003 and impact of nucleic acid testing (NAT).
AB  - Monitoring trends in residual risk of transfusion-transmitted viral infections is
      important to assess improvements in blood safety and to adapt the risk reduction
      policies. These trends were analysed in France over 4 periods of 3 years (1992
      1994, 1995-1997, 1998-2000 and 2001-2003). The 2001-2003 estimates were compared
      to the results of HIV-1 and HCV NAT implemented on all blood donations in July
      2001. Due to improvements in donor recruitment and selection, continuing progress
      in screening assays, and preventive measures taken in the community to control
      infections, a significant decrease was observed in residual risks for HIV, HCV
      and HBV between 1992 and 2003. The residual risk is currently extremely low: for
      the 2001-2003 period, this risk was estimated at 1 in 3.15 million donations for
      HIV, at 1 in 10 million for HCV and at 1 in 640,000 for HBV. Of the 6.14 million
      donations screened with NAT between July 2001 and December 2003 in France, 2 HIV
      positive and 3 HCV-positive donations were discarded thanks to NAT, representing
      a yield of 1 in 3.07 million for HIV and 1 in 2.05 million for HCV. These results
      show the limited benefit of NAT and suggest that its cost-effectiveness is poor.

PMID- 15735314
TI  - Incidence of viral markers and evaluation of the estimated risk in the Swiss
      blood donor population from 1996 to 2003.
AB  - Among the well known transfusion-associated risks, the transmission of pathogenic
      viruses is regarded as one of the most serious. Over the past two decades, a
      series of overlapping safety procedures have been successively implemented to
      minimise this risk. It is now generally considered that the risk of transmitting
      viral infections via blood products is very low in developed countries. The
      present study analyses the incidence of the key infectious diseases HIV,
      hepatitis B virus (HBV) and hepatitis C virus (HCV) between 1996 and 2003 from
      99% of voluntary repeat blood donors visiting the blood transfusion service of
      the Swiss Red Cross. Furthermore the estimated risk of these viral markers was
      calculated. From 1996 to 2003 the incidence rate for HCV decreased continuously,
      whereas no significant decrease in the incidence rate of HIV and HBV was
      observed. From 2001 to 2003, the last calculated period, the residual risk was
      estimated to be 1 in 1,900,000 for HIV, 1 in 2,200,0000 for HCV and 1 in 115,000
      for HBV, respectively. This agrees with international studies, which have been
      shown that the estimated residual risk for HBV between 1996 and 2003 is higher
      than that of HCV and HIV.

PMID- 15735315
TI  - Impact of nucleic acid amplification technology (NAT) in Italy in the three years
      following implementation (2001-2003).
AB  - The use of NAT technology to screen blood donations in Italy became mandatory on
      28 June 2002, but had been available experimentally since 2001. During the
      transition period, an EIA test to detect hepatitis C core antigen (HCVcoreAg) had
      also been permitted. Considering the large number of blood transfusion centres in
      Italy, an initial reorganisation of the biological validation of blood units was
      necessary, with a partial centralisation of NAT testing. The Gruppo Italiano per
      lo Studio delle Malattie Trasmissibili con la Trasfusione (Italian Group for the
      Study of Transfusion-Transmissible Diseases) conducted a national survey
      evaluating NAT testing, based on an annual collection of data through a
      questionnaire sent to all centres. In the first three years of the investigation,
      219 blood transfusion centres returned the questionnaires. In the period between
      January 2001 and December 2003, 3,894,894 blood donations were investigated for
      HCV RNA and 2,186,468 for HIV RNA. Of these, 12 were found to be HCV RNA positive
      and four HIV RNA positive, with an observed NAT versus antibody-based assay yield
      of 3.1/106 donations for HCV and 1.8/106 donations for HIV, respectively. Five of
      the 12 HCV RNA positive and anti-HCV negative donors had abnormal ALT values and
      their donations would have been discarded even in absence of NAT testing. Thus
      the final NAT yield for HCV is 1.79/106. The residual risk for HCV or HIV
      transmission by blood transfusion after NAT implementation is currently estimated
      to be extremely low in Italy.

PMID- 15735316
TI  - Blood safety and nucleic acid testing in Europe.

PMID- 15735317
TI  - Cancer biomarkers: an emerging means of detecting, diagnosing and treating
      cancer.

PMID- 15735319
TI  - TH01, a tetrameric short tandem repeat locus in the tyrosine hydroxylase gene:
      association with myocardial hypertrophy and death from myocardial infarction?
AB  - TH01 is a tetrameric short tandem repeat locus located in intron 01 of the
      tyrosine hydroxylase gene. The tyrosine hydroxylase catalyzes the hydroxylation
      of L-tyrosine to L-DOPA and is the rate limiting enzyme in the synthesis of
      catecholamines like noradrenaline or adrenaline, which are pivotal in the
      regulation of blood pressure. In a clinical study a strong correlation between
      alleles *9.3 and *10 and essential hypertension was observed ([2] Hypertension
      32: 676-682). To further investigate this association, we typed TH01 in 296
      autopsy cases and correlated the genotypes to the heart weight as parameter for
      myocardial hypertrophy. No significant correlation was observed. Moreover,
      dividing the studied cases into 2 groups, one including 172 casualties from
      hypertension-associated diseases (myocardial infarction, left heart failure,
      aortic aneurysm, spontaneous intracerebral bleeding and cerebral infarction) and
      one consisting of 124 cases of death unrelated to hypertension, revealed similar
      allelic frequencies for both groups. Our data thus suggest that TH01 long alleles
      appear not to lead to a significant increase in the incidence of myocardial
      hypertrophy or other hypertension associated diseases. This could be explained by
      a relatively small impact of the TH01 genotype on the blood pressure or by
      counteraction of another mechanism related to catecholamines and their effect on
      the human body.

PMID- 15735318
TI  - Polymorphisms in the promoter region of catalase gene and essential hypertension.
AB  - Genetic variations that predispose individuals to complex disorders, such as
      essential hypertension, may be found in gene coding regions, intronic regions or
      in gene promoter regions. Most studies have focused on gene variations that
      result in amino acid substitutions because they result in different isoforms of
      the protein, presumably resulting in differences in protein properties. Less
      attention has been placed on the role of intronic or promoter mutations. In this
      report, we examined two single nucleotide polymorphisms (SNPs) in the catalase
      (CAT) gene prompter region in a cohort of hypertensive Caucasians and African
      Americans with a Mass Spec based Homogenous MassEXTEND assay. We found an
      association when a specific combination of the two promoter SNPs was examined in
      Caucasians. No association was observed in African Americans. Our data suggest
      that genetic variations in the promoter region of catalase gene influence the
      susceptibility to essential hypertension. In addition, the genetic factors that
      contribute to hypertension maybe different between ethnic groups.

PMID- 15735320
TI  - Genetic variability of Apolipoprotein E in different populations from Venezuela.
AB  - The genetic variation at the Apolipoprotein E locus (APOE) is an important
      determinant of plasma lipids and has been implicated in various human
      pathological conditions. The objective of the present study was to estimate the
      distribution of APOE alleles in five Venezuelan communities: two Amerindian
      tribes (Bari and Yucpa), one Negroid population from Curiepe, one Caucasoid
      population from Colonia Tovar and the Mestizo urban population living in Caracas.
      The APOE*3 allele was the most common allele in all populations studied. However,
      a significant increase in the APOE*2 allele frequency in the Mestizo (18.96%) and
      Negroid (16.25%) populations was found. Similar to results reported in other
      Native American populations we have found that the APOE*2 allele is completely
      absent in the Bari and Yucpa Amerindians. Frequencies found in the Colonia Tovar
      population are in agreement with those reported in the population of Germany,
      indicating a high degree of relatedness. The results support the notion that the
      distribution of the APOE alleles shows ethnic variability.

PMID- 15735321
TI  - Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's
      disease).
AB  - Recent studies have demonstrated that alpha-Smooth Muscle actin expression in
      glomerular and tubulointerstitial compartments of renal tissue could represent a
      prognostic marker in several renal diseases. Our objective was to identify the
      prognostic value of alpha-SM actin actin expression on the evolution of renal
      damage in Primary IgA nephropathy (Berger's disease). 43 patients followed up
      from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirao
      Preto, University of Sao Paulo, Brazil, was studied. Clinical-laboratory data
      were obtained from the medical records of the patients using a protocol
      containing name, race, gender, origin, profession, age at clinical presentation
      of the disease and personal and family history. The parameters assessed in the
      approach to IgA nephropathy were serum creatinine, creatinine clearance, serum
      albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium,
      potassium, calcium and phosphorus ions, analysis of urinary sediment, serum
      complement profile, blood count, and renal biopsy. Morphological evaluation was
      performed by renal biopsy using common light and immunofluorescence microscopy.
      Immunohistochemical studies were performed using a murine monoclonal antibody to
      alpha-SM actin. Our data showed that alpha-SM actin expression in the glomerular
      and tubulointerstitial compartments are not correlated with unfavorable clinical
      course of primary IgA nephropathy.

PMID- 15735322
TI  - Complete mutation screening and haplotype characterization of the BRCA1 gene in
      61 familial breast cancer patients from Norway.
AB  - Mutations in the Breast-Cancer-1 (BRCA1) gene are the major cause of familial
      breast/ovarian cancer. Among familial breast cancer only, 15-20% have been
      suggested to have a deleterious mutation in BRCA1. A highly sensitive method (REF
      SSCP) was applied to screen the open reading frame and the 5'UTRs of BRCA1 for
      mutations. The patient cohort comprised 61 unrelated moderate to high risk breast
      cancer patients from Western-Norway. Only one known deleterious BRCA1 mutation
      (c.816-817delGT) was found in two of the 61 patients (3.3%). Four haplotypes were
      established based on nine known single nucleotide polymorphisms. Two patients had
      a novel deletion (c.-33_-29delAAAAA) in the 5'UTR, and a novel amino acid
      substitution (L523W) was found in one patient. Size variations analysis in the
      5'UTR was repeated in a cohort of 159 unrelated familial breast/ovarian cancer
      patients and 94 healthy blood donors. Two patients were identified with 5'UTR (c.
      30 to -60) variations (CAAAA)5 and (CAAAA)7, instead of the (CAAAA)6-repeat. All
      of the identified 5'UTR size variations were localized between the start codon
      and the most stable secondary structures previously proposed for the exon 1b
      transcript. No such alterations were found among the healthy blood donors but
      association studies of the 5'UTR variations within the respective families were
      not conclusive.

PMID- 15735323
TI  - Endostatin polymorphism 4349G/A(D104N) is not associated with aggressiveness of
      disease in prostate [corrected] cancer.
AB  - Endostatin is an important inhibitory molecule which mediates the sequential
      steps involved in angiogenesis. Lower level or impaired function of endostatin is
      associated with a higher risk of developing malignant solid tumors and with a
      worse prognosis of the disease. The endostatin N104 polymorphism might be
      associated with an impaired ability to inhibit angiogenesis. We analyzed the
      tissues from 98 Caucasian prostate cancer patients for the presence of D104N
      polymorphism. The frequencies of homozygous 4349G/G(104D/D), and heterozygous
      4349G/A(104D/N) were 83.67%(82/98) and 16.33%(16/98), respectively; no
      individuals were homozygous 4349A/A(104N/N). With the Fisher's exact test we
      found the genotype of D104N was not significantly related to age, tumor grade,
      PSA and clinical stage (P > 0.05). There was no difference in relapse free
      survival(RFS) or overall survival(OS) between patients with 104D/N and those with
      104D/D (P = 0.8283, 0.3713 respectively). We concluded that endostatin
      polymorphism was not associated with the aggressiveness of prostate cancer in
      Caucasian patients.

PMID- 15735324
TI  - RNA profiling for biomarker discovery: practical considerations for limiting
      sample sizes.
AB  - We have compared microarray data generated on Affymetrix chips from standard (8
      micrograms) or low (100 nanograms) amounts of total RNA. We evaluated the gene
      signals and gene fold-change estimates obtained from the two methods and
      validated a subset of the results by real time, polymerase chain reaction assays.
      The correlation of low RNA derived gene signals to gene signals obtained from
      standard RNA was poor for less to moderately abundant genes. Genes with high
      abundance showed better correlation in signals between the two methods. The
      signal correlation between the low RNA and standard RNA methods was improved by
      including a reference sample in the microarray analysis. In contrast, the fold
      change estimates for genes were better correlated between the two methods
      regardless of the magnitude of gene signals. A reference sample based method is
      suggested for studies that would end up comparing gene signal data from a
      combination of low and standard RNA templates; no such referencing appears to be
      necessary when comparing fold-changes of gene expression between standard and low
      template reactions.

PMID- 15735325
TI  - Nitric oxide synthase and arginase expression changes in the rat perirhinal and
      entorhinal cortices following unilateral vestibular damage: a link to deficits in
      object recognition?
AB  - Previous studies have shown that peripheral vestibular damage causes long-term
      neurochemical changes in the hippocampus which may be related to spatial memory
      deficits. Since recent studies have also demonstrated deficits in non-spatial
      object recognition memory following vestibular lesions, the aim of the present
      study was to extend these investigations into the perirhinal cortex (PRC), which
      is known to be important for object recognition, and the related entorhinal
      cortex (EC). We examined the effects of unilateral vestibular deafferentation
      (UVD) on the expression of four enzymes associated with neuronal plasticity,
      neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS),
      arginase I and arginase II (AI and II), in the rat EC and PRC using Western
      blotting. Tissue was collected at 10 hs, 50 hs and 2 weeks post-UVD. In the EC
      and PRC, nNOS protein expression decreased on the contralateral side at 2 weeks
      post-UVD but not before. At the same time, eNOS protein expression increased in
      both regions on the contralateral side. In the EC, AII protein expression
      increased on the ipsilateral side at 2 weeks post-UVD. In the PRC, AI increased
      and decreased on the contralateral and ipsilateral sides (respectively) at 2
      weeks post-UVD. AII showed a bilateral increase in the PRC at 2 weeks post-UVD.
      These results demonstrate changes in NOS and arginase protein expression in the
      PRC and EC following UVD, which are unlikely to be due to the initial severity of
      the vestibular syndrome because they develop well after vestibular compensation
      has taken place. Neurochemical changes in these regions of the medial temporal
      lobe may be implicated in the development of object recognition deficits that
      contribute to cognitive dysfunction following peripheral vestibular damage.

PMID- 15735326
TI  - System identification of the human vestibulo-ocular reflex during head-free
      tracking.
AB  - A method was developed to identify the linear, system level dynamics of the
      horizontal, angular vestibulo-ocular reflex (VOR) as it stabilized vision during
      head-free tracking of a visual target. Small amplitude, broad spectrum,
      stochastic torque perturbations were applied to the head while the subject
      tracked an unpredictable, moving target with active head and eye motions.
      Stochastic system identification techniques were used to design the torque and
      target inputs and to conduct the analysis such that the linear dynamics of the
      VOR, independently of the visual system's influence on eye motions, were
      determined. The linear analysis was limited to evaluating VOR dynamics from
      approximately 0.5 to 4.5 Hz. Nonlinearities in the head-neck system affected the
      low frequency response of the head to the torque perturbations, and the eye
      velocity sequence was affected by nonlinearities and degraded by noise at high
      frequencies. The VOR's gain was near 1.0 between about 0.5 and 2.5 Hz, and then
      decreased steadily to 0.85 as the frequency increased towards 4.0 Hz. The VOR
      phase angle was also frequency dependent and corresponded to VOR eye motions
      lagging the head's disturbance motion by less than 10 ms at frequencies greater
      than 1.0 Hz.

PMID- 15735327
TI  - Vestibular coriolis effect differences modeled with three-dimensional linear
      angular interactions.
AB  - The vestibular coriolis (or "cross-coupling") effect is traditionally explained
      by cross-coupled angular vectors, which, however, do not explain the differences
      in perceptual disturbance under different acceleration conditions. For example,
      during head roll tilt in a rotating chair, the magnitude of perceptual
      disturbance is affected by a number of factors, including acceleration or
      deceleration of the chair rotation or a zero-g environment. Therefore, it has
      been suggested that linear-angular interactions play a role. The present research
      investigated whether these perceptual differences and others involving linear
      coriolis accelerations could be explained under one common framework: the laws of
      motion in three dimensions, which include all linear-angular interactions among
      all six components of motion (three angular and three linear). The results show
      that the three-dimensional laws of motion predict the differences in perceptual
      disturbance. No special properties of the vestibular system or nervous system are
      required. In addition, simulations were performed with angular, linear, and tilt
      time constants inserted into the model, giving the same predictions. Three
      dimensional graphics were used to highlight the manner in which linear-angular
      interaction causes perceptual disturbance, and a crucial component is the Stretch
      Factor, which measures the "unexpected" linear component.

PMID- 15735328
TI  - Perceptual and nystagmic thresholds of vestibular function in yaw.
AB  - A technique for simultaneous measurement of conscious (perceptual) and reflex
      (nystagmus) thresholds of vestibular function is described. We used an automated
      modified binary search algorithm with simultaneous infrared oculography in
      determining perceptual and VOR nystagmic thresholds respectively, during discrete
      whole body rotations in the dark. In a young group of 14 normal subjects (mean
      age 23 years) angular acceleration thresholds were significantly higher for
      perceptual detection (1.18 deg/s/s) than for nystagmus generation (0.51 deg/s/s).
      Only nystagmic thresholds were slightly raised (0.87 deg/s/s) in an older group
      of 9 normal subjects (mean age 63 years). The finding that nystagmic thresholds
      are lower than perceptual ones indicates a higher sensitivity of brainstem than
      cortical vestibular mechanisms. This technique would be of particular value in
      clinical situations where a dissociation between reflex and conscious vestibular
      mechanisms is expected, e.g. in patients with cortical lesions or in elderly
      patients with falls.

PMID- 15735329
TI  - Tai Chi and vestibular rehabilitation effects on gaze and whole-body stability.
AB  - Tai Chi (TC) is a comparatively new intervention for peripheral vestibular
      hypofunction, which is often treated with vestibular rehabilitation (VR). We
      compared gaze stability (GZS), whole-body stability (WBS) and footfall stability
      (FFS) during locomotion among 26 people with vestibulopathy (VSP), randomized
      into two treatment arms (13 TC and 13 VR). Each intervention program was offered
      for 10 weeks. GZS improved more for VR than for TC, but WBS (and FFS) improved
      more for TC than for VR. There was a significant relationship between changes in
      GZS and WBS for the VR subjects (r=0.60, p=0.01), but not for TC subjects. There
      was a significant relationship between changes in WBS and FFS for both VR
      (r=0.65, p <0.01) and TC (r=0.58, p=0.02) groups; the relationship disappeared in
      the VR but not the TC group when controlling for GZS. These findings suggest that
      VR and TC both benefit patients with VSP but via differing mechanisms. Moreover,
      these data are the first to test the assumption that improving gaze control among
      patients with VSP perforce improves postural stability: it does not. We conclude
      that GZS is most improved in those who receive VR, but that TC improves WBS and
      FFS without improving GZS, suggesting patients with VSP can rely on non-gaze
      related mechanisms to improve postural control.

PMID- 15735330
TI  - Structural consequences of hen egg-white lysozyme orthorhombic crystal growth in
      a high magnetic field: validation of X-ray diffraction intensity, conformational
      energy searching and quantitative analysis of B factors and mosaicity.
AB  - A novel method has been developed to improve protein-crystal perfection during
      crystallization in a high magnetic field and structural studies have been
      undertaken. The three-dimensional structure of orthorhombic hen egg-white (HEW)
      lysozyme crystals grown in a homogeneous and static magnetic field of 10 T has
      been determined and refined to a resolution of 1.13 angstroms and an R factor of
      17.0%. The 10 T crystals belonged to space group P2(1)2(1)2(1), with unit-cell
      parameters a = 56.54 (3), b = 73.86 (6), c = 30.50 (2) angstroms and one molecule
      per asymmetric unit. A comparison of the structures of the 0 T and 10 T crystals
      has been carried out. The magnitude of the structural changes, with a root-mean
      square deviation value of 0.75 angstroms for the positions of all protein atoms,
      is similar to that observed when an identical protein structure is resolved in
      two different crystalline lattices. The structures remain similar, with the
      exception of a few residues e.g. Arg68, Arg73, Arg128 and Gln121. The shifts of
      the arginine residues result in very significant structural fluctuations, which
      can have large effects on a protein's crystallization properties. The high
      magnetic field contributed to an improvement in diffraction intensity by (i) the
      displacement of the charged side chains of Arg68 and Arg73 in the flexible loop
      and of Arg128 at the C-terminus and (ii) the removal of the alternate
      conformations of the charged side chains of Arg21, Lys97 or Arg114. The
      improvement in crystal perfection might arise from the magnetic effect on
      molecular orientation without structural change and differences in molecular
      interactions. X-ray diffraction and molecular-modelling studies of lysozyme
      crystals grown in a 10 T field have indicated that the field contributes to the
      stability of the dihedral angle. The average difference in conformational energy
      has a value of -578 kJ mol(-1) per charged residue in favour of the crystal grown
      in the magnetic field. For most protein atoms, the average B factor in the 10 T
      crystal shows an improvement of 1.8 angstroms(2) over that for the 0 T control;
      subsequently, the difference in diffraction intensity between the 10 T and 0 T
      crystals corresponds to an increase of 22.6% at the resolution limit. The
      mosaicity of the 10 T crystal was better than that of the 0 T crystal. More
      highly isotropic values of 0.0065, 0.0049 and 0.0048 degrees were recorded along
      the a, b and c axes, respectively. Anisotropic mosaicity analysis indicated that
      crystal growth is most perfect in the direction that corresponds to the favoured
      growth direction of the crystal, and that the crystal grown in the magnetic field
      had domains that were three times the volume of those of the control crystal.
      Overall, the magnetic field has improved the quality of these crystals and the
      diffracted intensity has increased significantly with the magnetic field, leading
      to a higher resolution.

PMID- 15735331
TI  - Urate oxidase from Aspergillus flavus: new crystal-packing contacts in relation
      to the content of the active site.
AB  - Urate oxidase from Aspergillus flavus (uricase or Uox; EC 1.7.3.3) is a 135 kDa
      homotetramer with a subunit consisting of 301 amino acids. It catalyses the first
      step of the degradation of uric acid into allantoin. The structure of the
      extracted enzyme complexed with a purine-type inhibitor (8-azaxanthin) had been
      solved from high-resolution X-ray diffraction of I222 crystals. Expression of the
      recombinant enzyme in Saccharomyces cerevisiae followed by a new purification
      procedure allowed the crystallization of both unliganded and liganded enzymes
      utilizing the same conditions but in various crystal forms. Here, four different
      crystal forms of Uox are analyzed. The diversity of the Uox crystal forms appears
      to depend strongly on the chemicals used as inhibitors. In the presence of uracil
      and 5,6-diaminouracil crystals usually belong to the trigonal space group
      P3(1)21, the asymmetric unit (AU) of which contains one tetramer of Uox (four
      subunits). Chemical oxidation of 5,6-diaminouracil within the protein may occur,
      leading to the canonical (I222) packing with one subunit per AU. Coexistence of
      two crystal forms, P2(1) with two tetramers per AU and I222, was found in the
      same crystallization drop containing another inhibitor, guanine. Finally, a
      fourth form, P2(1)2(1)2 with one tetramer per AU, resulted fortuitously in the
      presence of cymelarsan, an additive. Of all the reported forms, the I222 crystal
      forms present by far the best X-ray diffraction resolution (approximately 1.6
      angstroms resolution compared with 2.3-3.2 angstroms for the other forms). The
      various structures and contacts in all crystalline lattices are compared. The
      backbones are essentially conserved except for the region near the active site.
      Its location at the dimer interface is thus likely to be at the origin of the
      crystal contact changes as a response to the various bound inhibitors.

PMID- 15735332
TI  - Structure of Escherichia coli glutamate decarboxylase (GADalpha) in complex with
      glutarate at 2.05 angstroms resolution.
AB  - Glutamate decarboxylase (GAD) is a pyridoxal enzyme that catalyzes the conversion
      of L-glutamate into gamma-aminobutyric acid and carbon dioxide. The Escherichia
      coli enzyme exists as two isozymes, referred to as GADalpha and GADbeta. Crystals
      of the complex of the recombinant isozyme GADalpha with glutarate as a substrate
      analogue were grown in space group R3, with unit-cell parameters a = b = 117.1, c
      = 196.4 angstroms. The structure of the enzyme was solved by the molecular
      replacement method and refined at 2.05 angstroms resolution to an R factor of
      15.1% (R(free) = 19.9%). The asymmetric unit contains a dimer consisting of two
      subunits of the enzyme related by a noncrystallographic twofold axis which is
      perpendicular to and intersects a crystallographic threefold axis. The dimers are
      related by a crystallographic threefold axis to form a hexamer. The active site
      of each subunit is formed by residues of the large domains of both subunits of
      the dimer. The coenzyme pyridoxal phosphate (PLP) forms an aldimine bond with
      Lys276. The glutarate molecule bound in the active site of the enzyme adopts two
      conformations with equal occupancies. One of the two carboxy groups of the
      glutarate occupies the same position in both conformations and forms hydrogen
      bonds with the N atom of the main chain of Phe63 and the side chain of Thr62 of
      one subunit and the side chains of Asp86 and Asn83 of the adjacent subunit of the
      dimer. Apparently, it is in this position that the distal carboxy group of the
      substrate would be bound by the enzyme, thus providing recognition of glutamic
      acid by the enzyme.

PMID- 15735333
TI  - Structures of the DNA-binding site of Runt-domain transcription regulators.
AB  - Runt-domain (RD) proteins are transcription factors that play fundamental roles
      in various developmental pathways. They bind specifically to DNA sequences of the
      general form PyGPyGGTPy (Py = pyrimidine), through which they regulate
      transcription of target genes. The DNA duplex TCTGCGGTC/TGACCGCAG, incorporating
      the binding site for the RD transcription factors (bold), was crystallized in
      space group P4(3). X-ray analysis of two crystals diffracting to 1.7 and 2.0
      angstroms resolution, which had slight variations in their unit-cell parameters,
      revealed two distinct conformations of the A-DNA helix. The two crystal
      structures possessed several structure and hydration features that had previously
      been observed in A-DNA duplexes. A comparative analysis of the present A-DNA
      structures and those of previously reported B-DNA crystal structures of RD
      binding sites in free and protein-bound states showed the various duplexes to
      display several common features. Within this series, the present A-DNA duplexes
      adopt two conformations along the pathway from the canonical A-DNA to the B-DNA
      forms and the protein-bound helices display conformational features that are
      intermediate between those of the current A-DNA structures and that of the B-DNA
      type helix of the free RD target. Based on these data and energy considerations,
      it is likely that the propensity of the RD-binding site to adopt the A-DNA or B
      DNA conformation in solution depends on the sequence context and environmental
      conditions, and that the transition from either DNA form to the protein-bound
      conformation involves a small energy barrier.

PMID- 15735334
TI  - Strongly correlated structure of axial-symmetric proteins. I. Orthorhombic,
      tetragonal, trigonal and hexagonal symmetries.
AB  - The geometry of the molecular envelope and channel in axial-symmetric proteins is
      investigated in order to test the validity of rules deduced previously from
      several other biomacromolecules. Again, molecular forms with remarkable geometric
      properties are found. In particular, for order of rotation N = 2, 3, 4, 6 the
      molecular forms encapsulating the C(alpha) backbone of the protein have vertices
      at lattice points and therefore integral indices. These lattices are
      characterized by a height-to-width axial ratio that reduces the number of free
      parameters and enhances the symmetry.

PMID- 15735335
TI  - Strongly correlated structure of axial-symmetric proteins. II. Pentagonal,
      heptagonal, octagonal, nonagonal and ondecagonal symmetries.
AB  - The investigation of the geometry of the molecular envelope and channel in the
      proteins discussed in part I [Janner (2005a), Acta Cryst. D61, 247-255] is
      extended to axial-symmetric proteins with orders of rotation N = 5, 7, 8, 9 and
      11, non-crystallographic in dimension 3. In these cases also, the vertices of the
      molecular form which encapsulate the C(alpha) backbone have integral coordinates
      (indices) in a symmetry-adapted basis which generates a polygonal lattice. As in
      the crystallographic case of part I, a characteristic rational axial ratio
      squared is observed that reduces to one the number of free lattice parameters and
      enhances the symmetry. Furthermore, there is a crystallographic scaling relation
      between the envelope and the channel which depends on the order of the axial
      symmetry and is expressible in terms of star polygons. Possible biological
      implications are suggested within a more general context.

PMID- 15735336
TI  - Strongly correlated structure of axial-symmetric proteins. III. Complexes with
      DNA/RNA.
AB  - Three cases are considered of protein-DNA (or protein-RNA) complexes with a
      strongly correlated structure based on symmetry. In the first the symmetry of the
      nucleic acid is the determinant element, the second contains a dominant protein
      and an adaptive DNA/RNA and in the third a perturbed symmetry arises from
      elements of both components. The first situation is exemplified by the
      filamentous bacteriophage Pf1 in a low- and high-temperature state. The
      Pyrococcus abyssi Sm core and the trp RNA-binding attenuation protein are
      examples of the second situation. Finally, the nucleosome core particle
      represents the cooperative compromise between histone and DNA. In all the cases,
      the strong correlation in the structure is based on polygrammal scaling relations
      and on a molecular polygonal form lattice which depends on a single parameter.

PMID- 15735337
TI  - Structure of human uridine-cytidine kinase 2 determined by SIRAS using a rotating
      anode X-ray generator and a single samarium derivative.
AB  - Uridine-cytidine nucleoside kinase 2 (UCK2) is the rate-limiting enzyme in the
      pyrimidine-nucleotide salvage pathway. UCK2 catalyzes the phosphorylation of the
      natural ribonucleosides cytidine and uridine to cytidine 5'-monophosphate (CMP)
      and uridine 5'-monophosphate (UMP), respectively, and activates several important
      frontline antimetabolite drugs. The present contribution reports the rapid
      crystal structure determination of human UCK2 complexed with a magnesium ion and
      the reaction products adenosine 5'-diphosphate (ADP) and CMP. Diffraction data
      were collected on a copper rotating-anode X-ray generator from one native UCK2
      crystal and a single samarium-derivative crystal. Utilizing the relatively high
      anomalous signal from the samarium derivative at the Cu Kalpha wavelength, the
      structure was determined by single isomorphous replacement and single anomalous
      signal (SIRAS) phasing techniques. Two of the four major samarium sites are
      located in the active sites of the two UCK2 molecules that form the asymmetric
      unit and appear to displace the magnesium ions present in the native crystals.
      The crystal structures of UCK2 alone and in complex with various ligands have
      recently been determined using traditional multiple isomorphous replacement (MIR)
      phasing techniques and data from three heavy-atom derivatives. The reported
      structures validate our independently determined structure. Of more than 1000
      kinase crystal structure entries in the Protein Data Bank, less than 1% of them
      have been determined by SIRAS. For the published kinase crystal structures
      determined by SIRAS, all data were reportedly collected at various synchrotron
      radiation facilities. This study demonstrates that diffraction data collected
      from a single samarium derivative using Cu Kalpha radiation provides sufficient
      phasing power to determine a novel macromolecular crystal structure.

PMID- 15735338
TI  - Phased translation function revisited: structure solution of the cofilin-homology
      domain from yeast actin-binding protein 1 using six-dimensional searches.
AB  - A modified molecular-replacement method is described that makes use of six
      dimensional searches and the phased translation function, providing a systematic
      examination of all possible search-model orientations in an experimental electron
      density map. As an example, the structure solution of the cofilin-homology domain
      of the Saccharomyces cerevisiae actin-binding protein 1 (ABP1) is presented in
      detail. Additional examples are presented in which these tools have significantly
      aided structure solutions in a variety of contexts. These results suggest that
      this approach might be of widespread utility for challenging structures involving
      weak phase information, complex asymmetric units and search models with weak
      structural homology. Furthermore, this approach supports an exhaustive molecular
      replacement strategy in cases where an appropriate search model cannot readily be
      identified on the basis of sequence homology. The fully automated web-based
      implementation of this phased translation function is described.

PMID- 15735339
TI  - Structure of the type I L-asparaginase from the hyperthermophilic archaeon
      Pyrococcus horikoshii at 2.16 angstroms resolution.
AB  - The crystal structure of the L-asparaginase from the hyperthermophilic archaeon
      Pyrococcus horikoshii (PhA) was determined by the multiwavelength anomalous
      diffraction (MAD) method and was refined to a resolution of 2.16 angstroms with a
      crystallographic R factor and free R factor of 21.1 and 25.3%, respectively. This
      is the first report of the three-dimensional structure of a type I L
      asparaginase. These enyzmes are known as cytosolic L-asparaginases with lower
      affinities for substrate than the type II L-asparaginases. Although the overall
      fold of PhA was closely related to the structure of the well characterized type
      II L-asparaginase, structural differences were also detected. PhA forms a
      homodimer that corresponds to half the homotetramer of type II L-asparaginases.
      Structure comparison at the active site reveals that most catalytic residues are
      conserved except for two residues that recognize the amino group of the
      substrate. Additionally, a remarkable structural difference is found in the so
      called 'active-site flexible loop'. In PhA this loop is stabilized by beta
      hairpin formation and by elaborate interactions with the type-I-specific alpha
      helical region derived from the other subunit forming the PhA dimer. The flexible
      loop of the type II enzyme is considered to serve as a mobile gate to the active
      site. Therefore, the loop stabilization observed in the PhA structure may cause
      limitation of the access of the substrate to the active site.

PMID- 15735340
TI  - Structure of the zinc-induced heterodimer of two calcium-free isoforms of
      phospholipase A2 from Naja naja sagittifera at 2.7 angstroms resolution.
AB  - The crystal structure of a zinc-induced heterodimer of two metal-free isoforms of
      a cobra venom phospholipase A(2) has been determined at 2.7 angstroms resolution.
      The crystals belong to space group P4(1), with unit-cell parameters a = b = 65.5,
      c = 58.4 angstroms, and have a single dimer in the asymmetric unit. The structure
      has been refined to R(cryst) and R(free) factors of 0.188 and 0.232,
      respectively. The two isoforms have a sequence identity of 82%. The zinc ion
      forms a fivefold coordination with a trigonal bipyramidal geometry involving one
      O atom each from Asp24 and Asn112 from molecule A and Asp24 from molecule B and
      two water molecules. Both molecules of the dimer are inactive. Molecule A is
      inactive because Arg31 (B) binds to Asp49 (A), while an acetate ion has displaced
      the essential water molecule and interacts with His48 (A). On the other hand,
      Arg31 (A) interacts with the calcium-binding loop of molecule B, resulting in an
      altered conformation of the loop. The absence of a calcium ion, loss of the
      essential water molecule and the altered conformation of the calcium-binding loop
      may be the reasons for the loss of activity of molecule B.

PMID- 15735341
TI  - The 1.70 angstroms X-ray crystal structure of Mycobacterium tuberculosis
      phosphoglycerate mutase.
AB  - The single-crystal X-ray structure of phosphoglycerate mutase from Mycobacterium
      tuberculosis has been determined at a resolution of 1.70 angstroms. The C
      terminal tail of each of the subunits is flexible and disordered; however, for
      one of the four chains (chain A) all but five residues of the chain could be
      modeled. Noteworthy features of the structure include the active site and a
      proline-rich segment in each monomer forming a short left-handed polyprolyl
      helix. These segments lie on the enzyme surface and could conceivably participate
      in protein-protein interactions.

PMID- 15735342
TI  - Structure of recombinant human cyclophilin J, a novel member of the cyclophilin
      family.
AB  - Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl
      prolyl cis-trans isomerases. CyPs have also been identified as being a specific
      receptor for the immunosuppressive drug cyclosporin A and are involved in a
      variety of biological functions. CyPJ is a novel member of the CyP family and
      human CyPJ (hCyPJ) is the protein encoded by a cyclophilin-like gene from human
      foetal brain, which shows 50% sequence identity to human cyclophilin A (hCyPA).
      Recombinant hCyPJ was expressed in Escherichia coli and purified. The three
      dimensional structure of hCyPJ has been determined by molecular replacement using
      the hCyPA structure as the search model and has been refined at 2.6 angstroms
      resolution. The hCyPJ molecule contains four helices and one beta-barrel composed
      of eight antiparallel beta-strands. The overall secondary and tertiary structures
      of hCyPJ are similar to those of hCyPA, but hCyPJ contains an additional
      disulfide bridge and four segments with conformations that are strikingly
      different from those of hCyPA. His43 and Gln52 of hCyPJ are expected to be the
      active sites based on sequence alignment with hCyPA. The hCyPJ structure shows a
      conserved water molecule close to His43 and Gln52 which appears to support the
      solvent-assisted mechanism.

PMID- 15735343
TI  - Refinement of protein crystal structures using energy restraints derived from
      linear-scaling quantum mechanics.
AB  - A novel method is proposed in which combined restraints derived from linear
      scaling semiempirical quantum-mechanical (QM) calculations and X-ray diffraction
      data are combined to refine crystal structures of proteins. Its performance has
      been tested on a small protein molecule, bovine pancreatic trypsin inhibitor
      (BPTI). The refinement involves minimization of the sum of a geometric energy
      function and an X-ray target function based on either the least-squares residual
      or the maximum-likelihood formalism. For comparison, similar refinement runs have
      also been performed using energy restraints derived from the force field
      available in the Crystallography & NMR System (CNS) program. The QM refinements
      were carried out with weights that were varied by several orders of magnitude and
      the optimal weights were identified by observing the trend in the final free R
      values, QM heats of formation and coordinate root-mean-square deviations
      (r.m.s.d.s) from the crystal structure. It is found that the QM weights are
      typically smaller but generally on the same scale as the molecular-mechanics (MM)
      weights for the respective X-ray target functions. The crystallographic R, free
      R, real-space R values and correlation coefficients based on the structures
      refined with the energy restraints derived from our QM calculations and Engh and
      Huber parameters are comparable, suggesting that the QM restraints are capable of
      maintaining reasonable stereochemistry to a similar degree as the force-field
      parameters. A detailed inspection of the structures refined with the QM and MM
      energy restraints reveals that one of the common differences between them and the
      crystal structure is that the strained bond angles in the crystal structure are
      corrected after energetically restrained refinements. Systematic differences in
      certain bond lengths between the QM-refined structures and the statistical
      averages of experimental structures have also been observed and discussed.

PMID- 15735344
TI  - X-ray crystallographic studies of two transthyretin variants: further insights
      into amyloidogenesis.
AB  - Transthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set
      of not yet fully characterized conformational changes, forms fibrillar aggregates
      that are the major protein component of amyloid deposits. More than 80 mutations
      associated with TTR amyloid deposition have been described in the literature. X
      ray crystallography was used to elucidate the three-dimensional structure of two
      important TTR variants: TTR Y78F, an amyloidogenic protein, and TTR R104H, which
      is associated with a protective effect over the amyloidogenic V30M mutation. The
      structures of those two TTR variants have been determined in space group
      P2(1)2(1)2 to 1.55 and 1.60 angstroms resolution, respectively, using molecular
      replacement techniques. Detailed analysis of the protein model for TTR Y78F
      indicates a destabilization of the contacts between the alpha-helix and AB loop
      and the body of the molecule, intimately related to the amyloidogenic nature;
      contrastingly, in the TTR R104H variant new contacts involving the N-terminal
      region and His104 are clearly antagonists of amyloid formation.

PMID- 15735345
TI  - A novel cryoprotection scheme for enhancing the diffraction of crystals of
      recombinant cytochrome ba3 oxidase from Thermus thermophilus.
AB  - Cytochrome ba(3) oxidase is an integral membrane protein identified in the
      thermophilic bacterium Thermus thermophilus. The enzyme has now been expressed
      recombinantly and purified with a histidine tag. As such, it crystallizes under
      similar conditions and in the same space group (P4(3)2(1)2) as the native
      protein. A novel cryoprotection scheme is described here to obtain high
      resolution diffraction from these crystals, which involves soaking in a mixture
      of glycerol and ethylene glycol under a layer of oil. The unit-cell parameters
      for these crystals are larger than the native protein, apparently deriving from
      increased ordering of the N-terminus and an internal loop (residues 495-500) in
      subunit I. Hence, compared with native cytochrome ba(3) oxidase, the recombinant
      His-tagged protein is accommodated in an expanded but equally well ordered
      lattice via an alternate set of specific intermolecular contacts. The structure
      was refined against data to 2.3 angstroms resolution to an R factor of 21.7% and
      an R(free) of 23.7%.

PMID- 15735346
TI  - The use of high halide-ion concentrations and automated phasing procedures for
      the structural analysis of BclA, the major component of the exosporium of
      Bacillus anthracis spores.
AB  - The structure determination of the recombinant form of BclA, the major protein
      component of Bacillus anthracis exosporium, involved soaking in a high
      concentration of potassium iodide as the means of obtaining a good-quality heavy
      atom derivative. The data to 2 angstroms resolution collected on a laboratory
      source were of sufficient quality to allow successful phasing and chain tracing
      by automated methods.

PMID- 15735347
TI  - Unusual twinning in an acetyl coenzyme A synthetase (ADP-forming) from Pyrococcus
      furiosus.
AB  - A recombinant form of an acetyl coenzyme A synthetase (ADP-forming) from
      Pyrococcus furiosus has been crystallized. Crystallization was accomplished by
      the sitting-drop vapour-diffusion technique. Crystals belong to the monoclinic
      space group C2, with unit-cell parameters a = 131.3, b = 186.1, c = 121.5
      angstroms, beta = 122.6 degrees, and diffract to 2.0 angstroms resolution on a
      synchrotron-radiation source. The unit-cell parameters allow twinning to the
      higher apparent space-group symmetry F222 by twin-lattice quasi-symmetry. The
      twinning fraction for the data is close to 40%. Two other data sets in the PDB
      show similar twinning.

PMID- 15735348
TI  - Answering the questions about miniscrews.

PMID- 15735349
TI  - Clinical applications of the Miniscrew Anchorage System.

PMID- 15735350
TI  - Autotransplantation of impacted canines.

PMID- 15735351
TI  - Retaining treatment results with the advanceable twin-block appliance.

PMID- 15735352
TI  - Orthodontic treatment of a child with hereditary spherocytosis.

PMID- 15735353
TI  - Bonding a V-loop lingual retainer with a DuraLay transfer tray.

PMID- 15735354
TI  - A simple remedy for bond failure.

PMID- 15735355
TI  - The paperless office.

PMID- 15735356
TI  - Toothborne orthopedic maxillary protraction in Class III patients.

PMID- 15735357
TI  - Extraction space closure with vacuum-formed splints and miniscrew anchorage.

PMID- 15735358
TI  - Establishing an all-digital office.

PMID- 15735359
TI  - An oral screen for early intervention in lower-lip-sucking habits.

PMID- 15735360
TI  - Surgical-orthodontic management of a child with autism.

PMID- 15735361
TI  - Tsunami and the challenge for nutrition security.

PMID- 15735362
TI  - Trends in overweight, obesity and central fat accumulation among Tehranian adults
      between 1998-1999 and 2001-2002: Tehran lipid and glucose study.
AB  - AIMS: Recent estimates show the prevalence of obesity to be increasing at
      alarming rates. This study was conducted to examine trends of prevalence in
      overweight, obesity and central fat accumulation among Tehranian adults between
      1998 and 2002. METHODS: Height and weight of 2,102 adults, aged 20-80 years,
      participants of the Tehran Lipid and Glucose Study, were measured in 1998-1999
      and remeasured in 2001-2002, after 3 years. Criteria used to state prevalence of
      overweight and obesity were body mass index (BMI) 25-29.9 and > or =30,
      respectively. Central fat accumulation was defined as waist-hip ratio (WHR) > or
      =0.8 in women and > or =0.9 in men. Individuals were divided into 10-year groups
      and the prevalence of obesity was compared according to sex and age. RESULTS: In
      1998-1999 and 2001-2002, mean BMI was 26.1 +/- 4.1 and 26.7 +/- 4.1 kg/m(2) in
      men (p < 0.001) and 27.8 +/- 4.9 and 28.7 +/- 5.9 kg/m(2) in women (p < 0.001),
      respectively. Mean WHR in women was 0.84 +/- 0.08 in 1998-1999 and 0.88 +/- 0.08
      in 2001-2002 (p < 0.001). The prevalence of overweight in men was 42.5 and 46%
      and 40 and 39.5% in women in the two mentioned periods. The prevalence of obesity
      was 32.7 and 40.3% in men and 16.5 and 20.8% in women in 1998-1999 and 2001-2002
      respectively. In both sexes the fastest increasing trends in obesity and central
      fat accumulation were seen in the 30- to 40- and 20- to 30-year-old age groups.
      Comparison of the 50th percentile of BMI in all age groups showed a significant
      increase in 2001-2002 as compared to 1998-1999 (p < 0.01). CONCLUSION: The
      findings demonstrate significant rises in the prevalence of both total and
      central fat accumulation, calling for urgent action to educate people in
      lifestyle modifications.

PMID- 15735363
TI  - Erythrocyte plasma membrane perturbations in rats fed a cholesterol-rich diet:
      effect of drinking sulphurous mineral water.
AB  - AIMS: The purpose of the present study was to evaluate the ability of calcic and
      magnesic-sulphate-sulphurous spring mineral water (SMW) to reduce total and
      erythrocyte plasma membrane cholesterol in rats fed a cholesterol-rich diet.
      METHODS: By using different fluorescent probes, 1,6-diphenyl-1,3,5-hexatriene
      (DPH), 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH) and
      Laurdan, a possible correlation was evaluated between cholesterol content changes
      of the membranes and membrane fluidity. RESULTS: The results clearly show that
      hydropinic treatment reduced cholesterol level. No significant change was
      observed in DPH and TMA-DPH anisotropy values. By using Laurdan, an increase was
      observed in generalized polarization (GP(340)) in both groups of rats (the one
      that drank tap water and the one that drank SMW) compared with the controls. The
      rate of haemolysis was reduced in those erythrocyte suspensions in which
      cholesterol was increased, even if the enzymatic activity of glutathione
      peroxidase and catalase decreased. CONCLUSION: Hydropinic treatment with SMW is
      of interest from the biomedical point of view, because it could represent an
      alternative approach in interventions aimed at ameliorating biological injury
      deriving from hypercholesterolaemia.

PMID- 15735364
TI  - Food and nutrient intake, anthropometric measurements and smoking according to
      alcohol consumption in the EPIC Heidelberg study.
AB  - AIMS: The study was carried out to determine associations of reported alcohol
      intake with dietary habits, body mass index, waist-to-hip ratio (WHR) and
      smoking. SUBJECTS AND METHODS: 24,894 subjects who participated in the baseline
      examination of the German part of the European Prospective Investigation into
      Cancer and Nutrition (EPIC) in Heidelberg and were between 35 and 65 years of age
      at baseline were included in the present cross-sectional analysis (11,617 men,
      13,277 women). Diet and alcohol consumption were assessed with a semiquantitative
      food frequency questionnaire. Analysis of covariance with age as a covariate was
      used to analyse the association between alcohol intake and dietary consumption
      patterns, BMI, WHR and smoking. RESULTS: Alcohol did not replace other food
      items, but was an addition to the diet. Among alcohol consumers, fat and protein
      intake as a percentage of energy was slightly higher and carbohydrate intake was
      slightly lower than among abstainers. Alcohol consumers had a lower intake of
      fruits, dairy products, cereal products, and added vegetable fat and a higher
      intake of animal products such as meat, fish, eggs and added animal fat than
      abstainers. The prevalence of current smoking showed a U-shaped relation to
      alcohol intake in men and women. In men, a U-shaped association was also seen
      between the prevalence of former smoking and alcohol intake, while the prevalence
      of former smoking increased linearly with alcohol intake in women. CONCLUSION:
      The results show that alcohol consumption is associated with dietary consumption
      patterns and smoking. Therefore, it will be important to consider dietary
      patterns and other lifestyle parameters when investigating the health effects of
      alcohol intake in the future.

PMID- 15735365
TI  - Serum concentration of vitamins A and E and lipid in a rural population of north
      Cameroon.
AB  - BACKGROUND: Vitamin A deficiency is still a major health problem mostly affecting
      people in developing countries. It contributes to increased mortality and
      morbidity through current infection. In Cameroon, it is a public health problem
      mostly in the northern part where palm oil, which is a principal source of
      provitamin A in the south of the country, is not consumed. AIM: We carried out
      this research to discover the relationship between vitamins (A and E) and blood
      lipids in a normal rural population living in vitamin A-deficiency area. DESIGN:
      A cross-sectional study with 81 healthy volunteers (40 men and 41 women) aged 3
      61 (mean 18.32 +/- 1.63) years and living in two neighboring villages (Doyan and
      Larao) in the northern part of Cameroon, where previous studies revealed a
      prevalence of vitamin A deficiency of 33.3%. METHODS: Serum concentrations of
      vitamins A and E were measured by fluorometric methods. Serum cholesterol and
      lipids were assayed by enzymatic methods. RESULTS: The mean +/- standard error
      for vitamin A and E were 15.09 +/- 0.82; 526.99 +/- 29.57 mug/100 ml,
      respectively. The concentrations of the serum parameters analyzed were similar
      for both sexes, whereas the atherogenic ration of cholesterol (ARC) was
      significantly (p < 0.036) higher in women. Serum lipids (total lipids, total
      cholesterol, low-density lipoprotein and phospholipids) correlated with vitamins
      A and E (p < 0.05). Vitamins A and E were highly correlated with each other (r =
      0.42, p < 0.001). Age was positively associated with vitamin A (r = 0.42, p <
      0.001) and vitamin E (r = 0.29, p < 0.01). Deficiency of vitamins A and E
      constitutes a public health problem with more than 56% of the subjects having low
      levels of these vitamins, while subjects tested had a low risk for cardiovascular
      diseases. CONCLUSION: In this population we noticed normal lipid levels and
      vitamin A deficiency probably resulting from diets poor in provitamin A.

PMID- 15735366
TI  - Isoflavones improve plasma homocysteine status and antioxidant defense system in
      healthy young men at rest but do not ameliorate oxidative stress induced by 80%
      VO2pk exercise.
AB  - AIMS: (1) Determination of whether isoflavones, as antioxidants and estrogen-like
      substances, reduce the atherosclerotic process. (2) Assessment of isoflavone anti
      atherosclerotic effectiveness by means of measuring plasma markers of
      atherosclerosis: homocysteine (Hcy), antioxidant status, and lipid peroxidation.
      (3) Testing of isoflavone antioxidant effectiveness in the presence and absence
      of oxidative stress induced by exercise. METHODS: Thirty subjects paired by
      aerobic fitness level were randomly assigned to either a placebo or high
      genistein isoflavone extract (HGI, 150 mg/day) treatment. Blood samples were
      collected before and within 5 min, after 30 min at 80% peak oxygen consumption
      (VO(2)pk) exercise, and before and after 4-week supplementation. RESULTS: Plasma
      genistein and daidzein were significantly increased by 4-week HGI supplementation
      before and after exercise (p < 0.05). HGI decreased pre-exercise (pre-ex) plasma
      malondialdehyde (MDA) (p < 0.05) and Hcy (p = 0.01), and increased pre-ex blood
      total glutathione (TGSH) (p = 0.01), but did not diminish the increase of MDA and
      the decrease of TGSH due to the exercise. Furthermore, HGI supplementation
      enhanced pre-ex total antioxidant capacity (p < 0.05), but did not influence
      plasma vitamin C and E and uric acid concentrations. CONCLUSION: Isoflavones
      reduce plasma Hcy and have antioxidant activity in healthy young men. However,
      the effect of isoflavones on antioxidant systems may not be potent enough to
      diminish an abrupt surge of oxidative stress due to acute exercise.

PMID- 15735367
TI  - Effect of supplementation with docosahexaenoic acid ethyl ester and sn-2
      docosahexaenyl monoacylglyceride on plasma and erythrocyte fatty acids in rats.
AB  - BACKGROUND/AIMS: Docosahexaenoic acid (C22:6, DHA) is an omega-3 fatty acid
      required for the normal development of the mammalian nervous and visual system.
      DHA is provided by the mother during pregnancy and lactating period. Mother's DHA
      supplementation during pregnancy, and even before pregnancy, has been suggested.
      DHA can be provided by marine oils, egg's yolk phospholipids, single cell algae
      oils, the pure fatty acid, or by the ethyl ester derivative (DHA-EE). Another way
      to provide DHA can be by sn-2 docosahexaenyl monoacylglyceride (DHA-MG), obtained
      by the treatment of fish oil with stereospecific lipases. sn-2 Fatty acid
      monoacylglycerides can be more easily absorbed at the intestine than other fatty
      acid derivatives. METHODS: Female rats fed with a synthetic, which provided
      essentially no DHA, received a 40-day supplementation of either DHA-EE or DHA-MG.
      Plasma and erythrocyte fatty acid composition were assessed by gas chromatography
      at day 0 and 40 of supplementation. RESULTS: DHA-EE increased plasma and
      erythrocyte DHA by 15 and 11.9%, respectively, with no modification of
      arachidonic acid (AA) content. DHA-MG supplementation increased plasma and
      erythrocyte DHA by 24 and 23.8%, respectively, but reduced AA by 5.5 and 3%,
      respectively. CONCLUSIONS: We conclude that in the rat, DHA-MG supplementation
      allows a higher plasma and erythrocyte DHA content than DHA-EE with minor
      modification of AA content.

PMID- 15735368
TI  - TEAVIGO (epigallocatechin gallate) supplementation prevents obesity in rodents by
      reducing adipose tissue mass.
AB  - BACKGROUND: This study investigated the antiobesity effects of TEAVIGO, a product
      providing the most abundant green tea catechin, epigallocatechin gallate (EGCG),
      in a pure form. Two models of diet-induced obesity and an in vitro adipocyte
      differentiation assay were employed. METHODS: Prevention and regression of diet
      induced obesity by dietary supplementation with EGCG was studied in C57BL/6J mice
      and Sprague-Dawley rats, respectively. Expression of genes regulating lipid
      metabolism was assessed in adipose tissue. The effects of EGCG on adipocyte
      differentiation were investigated in vitro. RESULTS: In C57BL/6J mice, EGCG
      supplementation prevented diet-induced increases in body weight and in fed state
      plasma levels of glucose, triglycerides, and leptin. EGCG decreased subcutaneous
      and epididymal adipose tissue weights. Supplementation of EGCG reversed the
      established obesity in Sprague-Dawley rats. Fatty acid synthase and acetyl-CoA
      carboxylase-1 mRNA levels were markedly decreased in adipose tissue of EGCG
      supplemented mice. EGCG dose dependently inhibited adipocyte differentiation in
      vitro. CONCLUSION: This study shows for the first time that supplementation with
      the most abundant green tea polyphenol, EGCG, abolishes diet-induced obesity.
      This effect is at least partly mediated via a direct influence on adipose tissue.
      Thus, dietary supplementation with EGCG should be considered as a valuable
      natural treatment option for obesity.

PMID- 15735369
TI  - Assessment of nutritional intake, body mass index and glycemic control in
      patients with type-2 diabetes from northern Tanzania.
AB  - BACKGROUND/AIMS: Little information is available about the nutrition of people
      with diabetes from Africa. For the treatment and prevention of diabetes by
      nutrition, we have assessed the major local foods in a baseline study. METHODS:
      The staple foods and meal frequencies of 53 outpatients with type-2 diabetes were
      assessed in a 24-hour dietary recall based on a questionnaire at a diabetes
      clinic in northern Tanzania in November and December 1999. In addition, data on
      weight and height, casual blood glucose, urinary glucose and diabetes therapy
      were ascertained. RESULTS: 72% of the patients had a body mass index of > or =25
      kg/m(2); 64% of patients had casual blood glucose levels of >7.8 mmol/l, 47% had
      >11.1 mmol/l, and most of them were treated by sulfonylureas or conventional
      insulin therapy. The test for urinary glucose highly correlated with the blood
      glucose values, and was positive in 59% of patients. 36% of the patients had < or
      =3 meals/day. The foods stated most frequently were stiff porridge, plantains,
      bread, rice, beef, milk, amaranth leaves, orange and sunflower oil. The main
      beverages were water, tea and milk. CONCLUSIONS: The baseline data obtained
      enable more precise dietary assessment and emphasize the need to collect more
      data on local food consumption in areas where pharmacological diabetes treatment
      is limited.

PMID- 15735370
TI  - Altered metabolic profiles among older mothers with a history of preeclampsia.
AB  - Preeclampsia has been linked to increased risk for cardiovascular disease and,
      more recently, to reduced risk for breast cancer later in life. The altered
      chronic disease risk associated with prior preeclampsia may reflect underlying
      metabolic differences. In this case-control study, we examined the metabolic
      profiles of older mothers with and without a history of preeclampsia in their
      first pregnancies. At the time of the study, subjects were non-pregnant, non
      smoking women who completed their first pregnancies at age 30 or older, were pre
      menopausal, and were free of serious chronic disease. Cases were 13 women who
      experienced preeclampsia in their first pregnancies; controls were 13 women with
      uncomplicated first pregnancies, frequency matched to cases on race/ethnicity,
      current age, and age at delivery. A fasting blood sample was collected from each
      subject during the luteal phase (day 19-22) of the menstrual cycle and assayed
      for specific factors thought to be linked to hypertensive disease or breast
      cancer. Compared to women with uncomplicated pregnancies, those with a history of
      preeclampsia had significantly elevated levels of fasting serum triglycerides,
      insulin and glucose, and a higher fasting insulin resistance index, suggesting
      that women with prior preeclampsia were relatively insulin resistant. In
      addition, cases had higher levels of insulin-like growth factor (IGF)-binding
      protein-3 (IGFBP-3) and a higher molar ratio of IGFBP-3 to IGF-1 than did
      controls. Adjustment for obesity and other potential confounders did not
      appreciably alter the magnitude of these associations. This preliminary study
      suggests that women with a history of preeclampsia have persistent metabolic
      abnormalities consistent with their observed excess risk for cardiovascular
      morbidity and mortality, and their apparent reduced risk for breast cancer later
      in life.

PMID- 15735371
TI  - Total pubertal growth and markers of puberty onset in adolescents with GHD:
      comparison between mathematical growth analysis and pubertal staging methods.
AB  - Two methods of determining puberty onset (Preece- Baines model 1 (PB1) and Tanner
      staging) were used to calculate total pubertal growth (TPG) in adolescents with
      growth hormone deficiency (GHD). PATIENTS AND METHODS: 34 patients (11 girls) met
      the following inclusion criteria: isolated GHD, >2 years growth hormone therapy
      prior to puberty onset, regular weight-adjusted GH dosage, known final height
      (age >21 years or height velocity <0.5 cm/year), no induction of puberty. PB1 was
      used to define age and height at onset of the pubertal growth spurt ("take-off").
      RESULTS: The results (mean +/- SD) were as follows: in girls, mean age at take
      off was 9.8 years; 2.0 +/- 1.1 years before breast stage B2. In boys, mean age at
      take-off was 11.3 years; 1.4 +/- 0.8 years before testes volume >3 ml. Height at
      take-off was lower than at Tanner stage 2 by 12.4 +/- 7.6 cm in girls and 7.7 +/-
      5.3 cm in boys. TPG was thus markedly greater (p < 0.001) using the PB1 method,
      as compared with Tanner stage2. Peak height velocity was normal. Final height was
      -0.5 +/- 0.7 SDS in females and -0.4 +/- 0.9 SDS in males. CONCLUSIONS: The
      method of measuring TPG from take-off is more objective, and has potentially
      greater implications for GH therapeutics than the Tanner stage method. In our
      study, 40% of TPG occurred before "breast stage B2" was attained in GHD girls;
      whereas 23% of TPG occurred before "testes >3 ml" in GHD boys.

PMID- 15735372
TI  - Clinicopathologic study of non-Hodgkin lymphoma in sinonasal and hard palate
      regions in 15 Japanese cases.
AB  - Non-Hodgkin lymphomas of the sinonasal region have been the subject of numerous
      studies. Previous reports have suggested that nasal lymphomas occurring in
      Orientals are mostly of the natural killer cell (NK)/T-cell phenotype which
      contrasts with the preponderance of the B-cell type in western populations.
      Recent studies indicated that NK/T-cell lymphoma constitutes the clinical
      condition of lethal midline granuloma. These reports led us to question whether
      all NK/T lymphomas are always lethal midline granuloma. We have investigated a
      series of 15 cases of non-Hodgkin lymphomas in the nasal and/or paranasal sinuses
      clinically, immunohistochemically and for the presence of Epstein-Barr virus
      (EBV). This study showed that the presence of EBV was common in nasal NK/T
      lymphoma, and this type of lymphoma was clearly highly frequent in other types of
      nasal lymphoma in our department. Moreover, in 4 cases of NK/T-cell lymphomas,
      the clinical features of lethal midline granuloma did not appear, indicating that
      NK/T lymphomas are not always lethal midline granuloma.

PMID- 15735373
TI  - Emergency extracorporeal shockwave lithotripsy for acute renal colic caused by
      upper urinary-tract stones.
AB  - PURPOSE: To evaluate emergency SWL for the treatment of upper urinary-tract
      stones causing renal colic. PATIENTS AND METHODS: Between January 1999 and June
      2003, 53 patients with a mean age of 46.6 years (range 22-65 years) were
      enrolled. The inclusion criteria were acute renal colic, radiopaque 5-mm to 1.5
      cm calculi in the ureteropelvic junction (N=10) or upper ureter (N=43), and no
      evidence of urinary-tract infection or acute renal failure. The mean stone size
      was 7.14 mm (range 5-13 mm). Patients were randomly assigned to the control
      (N=28) and study (N=25) groups using previously prepared cards in envelopes.
      Patients in the study group underwent emergency SWL, while patients in the
      control group underwent scheduled SWL within 30 days. Stone status was evaluated
      4 weeks after lithotripsy. There was no significant difference between the
      control and study groups with respect to age, sex, stone location or volume,
      renal obstruction, or days spent in the hospital for pain control. Available
      fragments of stones were sent for infrared spectroscopy. Preoperative and
      postoperative data were compared in the two groups using SPSS 10.0 statistical
      software. RESULTS: The SWL treatment lasted 50+/-11 minutes. The stone-free rates
      were 72% and 64% and the efficiency quotients were 53% and 44% in study and
      control groups, respectively. Patients in the control group spent more time in
      the hospital (P=0.014) and in recovery at home (P=0.011). CONCLUSION: Emergency
      SWL for acute renal colic caused by upper-ureteral stones is a safe procedure and
      offers effective release from pain and obstruction. It also decreases
      hospitalization days and hastens return to normal activity.

PMID- 15735374
TI  - CT attenuation value and shockwave fragmentation.
AB  - PURPOSE: To evaluate whether, in principle, the mean CT attenuation values of
      kidney stones could predict fragmentation by shockwaves. MATERIALS AND METHODS:
      Four types of artificial kidney stones having different CT attenuation values
      were tested. Artificial stones were weighed and exposed to 700 shockwaves at 21
      kV at the focus of an electrohydraulic lithotripter. Fragments were strained
      through meshes with 2x2-mm and 3.1x3.1-mm openings. The material left on the
      meshes after shockwave exposure was dried and weighed on a precision scale. Half
      of all artificial stones were saturated by immersing them in water several days
      before fragmentation. Fragmentation coefficients (i.e., percent weight loss) were
      associated with CT attenuation values using a statistical model. RESULTS: Higher
      CT numbers resulted in lower fragmentation coefficients. Artificial stone weight
      was inversely proportional to the percent weight loss. Larger fragments were
      obtained at lower fragmentation coefficients. Statistical analysis revealed that
      fragmentation can be predicted knowing the weight and the CT number of a stone
      before shockwave application. CONCLUSION: Prediction of the number of shockwaves
      necessary for successful SWL could be possible. Our statistical model proved to
      fit in vitro fragmentation of artificial stones; however, clinical application
      requires further research.

PMID- 15735375
TI  - Shockwave therapy as first-line treatment for Peyronie's disease: a prospective
      study.
AB  - BACKGROUND AND PURPOSE: To assess in a prospective study whether shockwave
      therapy (SWT) is effective as a first-line treatment for Peyronie's disease.
      PATIENTS AND METHODS: Forty patients with previously untreated Peyronie's disease
      underwent SWT with the Epos overhead-module device (Dornier). The pain severity
      (visual analog pain scale [VAS] 0-5), the degree of penile angulation after
      vasoactive drug injection, plaque size by ultrasound measurement, and erectile
      dysfunction (IIEF score) were assessed prior to and after treatment. Of the 40
      patients, 7 underwent two sessions and the rest three sessions. The time interval
      between treatments was 2 weeks. At a power level of 2 to 5 (mean 4), a maximum of
      3000 shockwaves per plaque per treatment were applied. The mean follow-up was 12
      months. RESULTS: All patients completed the protocol. The tolerance and safety
      were excellent. Of the 25 patients with pain on erection, 12 (48%) noticed relief
      after the first session, while 9 more were pain free at the end of the treatment
      (VAS reduction 2.8; P<0.0001, and 2; P<0.001, respectively). For 25 patients
      (62.5%), an improvement in penile angulation>20 degrees was observed, with a mean
      reduction of 35 degrees (range 20 degrees-60 degrees ) (P<0.001). No significant
      change in plaque size was noted. Among 28 patients with erectile dysfunction, 18
      (64.2%) had a marked increase in erection quality (IIEF score change: +4 for 10
      patients, +6 for 4 patients, +8 for 2 patients, +9 for 2 patients). CONCLUSION:
      Our results support SWT as an effective and safe first-line treatment for
      Peyronie's disease.

PMID- 15735376
TI  - Current trends in urologic laparoscopic surgery.
AB  - PURPOSE: We examined the status of laparoscopy in urology and the impact of
      residency and fellowship training on the performance of laparoscopy as primary
      surgeon. We also examined whether performing nonsurgical tasks requiring two
      handed dexterity had any link to the adoption of laparoscopic techniques by
      urologists. MATERIALS AND METHODS: A total of 8760 laparoscopy questionnaires
      containing 135 queries were mailed to urologists listed on the American
      Urological Association practicing urologists mailing list. The questions sought
      information on area of practice, time in practice, fellowship training,
      ambidexterity, laparoscopic experience, and experience with robotics. The
      response rate was 1.8% (155 of 8760). RESULTS: There appeared to be no
      significant correlation between the performance of laparoscopic surgery and
      participation in activities requiring bimanual dexterity. However, a correlation
      of strong statistical significance did exist between laparoscopic residency
      training and performance of laparoscopy after residency (p=0.003. There also was
      a correlation between fellowship training in laparoscopy/endourology and doing
      laparoscopy as primary surgeon. CONCLUSIONS: Participation in laparoscopic
      surgery during residency training is a major determining factor in performance of
      laparoscopy as a primary surgeon in practice. Younger surgeons trained in
      laparoscopy during residency are performing more laparoscopy post residency than
      those without laparoscopic training during residency. At present, there is a need
      to train more urologists in laparoscopy at the postgraduate level.

PMID- 15735377
TI  - Laparoscopic partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: With continuing rapid changes in endourology, we
      conducted a new survey of practice trends and expanded our sampling to include
      non-American urologists. MATERIALS AND METHODS: The survey was done via the
      Internet using the database for the 2003 World Congress of Endourology.
      Approximately 1100 surveys were sent, and responses were received from 193
      urologists, who had been in practice for a mean of 9.9 years (median 8 years). Of
      these, 52% spend >50% in endourology, and 48% devote >20% of their practice to
      laparoscopy. RESULTS: More than half of the respondents (56%) perform
      laparoscopic partial nephrectomy (LPN), and 65% chose LPN as the procedure of
      choice for patients with an uncomplicated 3-cm renal mass. The majority obtain
      vascular control, most commonly by clamping the renal artery only. Most
      respondents do not use ureteral stents unless the collecting system is entered.
      CONCLUSIONS: These results and a review of the literature indicate a growing
      acceptance among endourologists of LPN as the procedure of choice for patients
      with small renal masses who are to undergo nephron-sparing surgery. Disagreement
      remains concerning the role and type of vascular control, the use of hemostatic
      agents, and the value of stents when the collecting system is entered.

PMID- 15735378
TI  - High-power thulium fiber laser ablation of urinary tissues at 1.94 microm.
AB  - PURPOSE: This paper describes the preliminary testing of a new laser, the thulium
      fiber laser, as a potential replacement for the holmium:YAG laser for multiple
      applications in urology. MATERIALS AND METHODS: A 40 W thulium fiber laser
      operating at a wavelength of 1.94 microm delivered radiation in a continuous-wave
      or pulsed mode (10 msec) through either 300-microm- or 600-microm-core low-OH
      silica fibers for vaporization of canine prostate and incision of animal ureter
      and bladder-neck tissues. RESULTS: The thulium fiber laser vaporized prostate
      tissue at a rate of 0.21+/-0.02 g/min. The thermal-coagulation zone measured 500
      to 2000 microm, demonstrating the potential for hemostasis. Laser incisions were
      also made in bladder tissue and ureter, with coagulation zones of 400 to 600
      microm. CONCLUSIONS: The thulium fiber laser has several potential advantages
      over the holmium laser, including smaller size, more efficient operation, more
      precise incision of tissues, and operation in either the pulsed or the continuous
      wave mode. However, before clinical use will be possible, development of higher
      power thulium fiber lasers and shorter pulse lengths will be necessary for rapid
      vaporization of the prostate and more precise incision of urethral/bladder-neck
      strictures, respectively.

PMID- 15735379
TI  - Wireless teleradiology for renal colic and renal trauma.
AB  - BACKGROUND PURPOSE: Image transmission is an integral part of telemedicine,
      allowing evaluation of patients at remote sites. We developed a simple method of
      wireless transmission of digital images to a hand-held computer (PDA) and
      evaluated its feasibility and diagnostic accuracy in patients with acute renal
      colic or renal trauma. MATERIALS AND METHODS: The CT images from 11 patients with
      suspected renal colic and one patient with renal trauma were transmitted using a
      cellular telephone with a wireless modem link to a PDA (Sony Clie 615C). A
      diagnostic interpretation was recorded for the presence/absence of an upper-tract
      stone, stone location, estimated stone size, and signs of upper-tract
      obstruction. Radiologic staging of trauma was provided in the patient with a
      renal injury. Comparison was made with the final dictated report of a staff
      radiologist. RESULTS: Ten CT sets of patients with renal colic were used for
      comparison, the remaining one being excluded because of ambiguity in the final
      radiology report. An average of 5.9+/-1.6 images, average size 32.2+/-5.2 kb
      (range 21-42 kb) for each patient were sent at an average speed of 1 kb/sec.
      Interpretation correctly identified stone presence in 80%, hydronephrosis in
      100%, and perinephric stranding in 80% and stone size within 1+/-1 mm. A stage-3
      renal trauma was correctly identified and staged. CONCLUSION: Wireless
      teleradiology to PDA units provides image quality sufficient for diagnostic
      interpretation. Anticipated improvements in wireless transmission and PDA screen
      image resolution will enhance the speed, quality, and quantity of images
      transmitted. Wireless teleradiology may facilitate convenient rapid evaluation of
      patients at remote sites.

PMID- 15735380
TI  - Virtual endoscopy: navigation within pelvicaliceal system.
AB  - PURPOSE: To evaluate the use of virtual endoscopy (VE) for the investigation of
      the pelvicaliceal unit and the depiction of its anatomic deformities. PATIENTS
      AND METHODS: Two study groups were prospectively enrolled in our protocol: ten
      patients with nonurologic pathologies, and thus without any known deformity of
      the pelvicaliceal unit (group A), and five patients with caliceal obstruction
      (group B). Virtual endoscopy represented a non-invasive technique providing
      amplification of the image in three-dimensional space. RESULTS: Virtual endoscopy
      was feasible in all patients, and in all cases succeeded in demonstrating the
      threedimensional morphology of the region of interest. The entire processing time
      ranged from 10 to 15 minutes (mean 12.6 minutes), and the three-dimensional image
      could be viewed from different angles, allowing better evaluation of the
      collecting system and its deformities than is possible with conventional
      intravenous urography or percutaneous nephrostomography. CONCLUSION: Virtual
      endoscopy enabled the creation of endoluminal views of the renal pelvis and
      calices from spiral tomographic images, thereby allowing diagnostic-preoperative
      and postoperative evaluation of the pelvicaliceal unit.

PMID- 15735381
TI  - Contemporary management of ureteropelvic junction obstruction: practice patterns
      in Minnesota.
AB  - BACKGROUND AND PURPOSE: Ureteropelvic junction (UPJ) obstruction can be addressed
      surgically by an open, laparoscopic, endoscopic, or fluoroscopic procedure. Our
      objective was to establish what surgical alternatives are currently offered by
      urologists in Minnesota. MATERIALS AND METHODS: A questionnaire was sent to 174
      members of the Minnesota Urological Society. Practice settings were characterized
      as rural, urban, or metropolitan on the basis of the ZIP-code classifications of
      the Minnesota Ambulance Association and state geographic legislation. Respondents
      were asked to select initial treatment options for an adult patient with flank
      pain, decreased renal function, and hydronephrosis secondary to UPJ obstruction.
      RESULTS: Whereas 60% of the respondents would offer open pyeloplasty, only 12%
      would offer it as the only treatment option. The two most common minimally
      invasive therapies offered were the Acucise balloon (48%) and percutaneous
      antegrade endopyelotomy (48%). Rural urologists were more likely to offer Acucise
      balloon incision (71%) than were urban (28%; P=0.045) or metropolitan (55%;
      P=0.412) urologists. CONCLUSIONS: The majority of urologists still offer open
      pyeloplasty as first-line therapy for UPJ obstruction. Further emphasis should be
      placed on increasing the availability of endoscopic and laparoscopic procedures.

PMID- 15735382
TI  - Nephrolithiasis: "scope," shock or scalpel?
AB  - PURPOSE: To evaluate treatment preferences for complex urinary calculi. MATERIALS
      AND METHODS: A questionnaire was sent to 174 members of the Minnesota Urological
      Society. Three case scenarios were presented: a 1.5-cm lower-pole calculus with
      unfavorable anatomy, a 1.4-cm proximalureteral calculus, and a staghorn calculus.
      The treatment options offered were extracorporeal shockwave lithotripsy (SWL),
      ureteral stenting, ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), and
      open surgery. RESULTS: Our survey response rate was 49%. A PCNL for staghorn
      calculi was more likely to be offered by urologists in metropolitan (100%;
      P<0.001) and urban (100%; P=0.003) settings than rural settings (57%). Whereas
      only 22% of urban and metropolitan urologists would offer anatrophic
      nephrolithotomy, 43% of rural urologists would include this among their treatment
      options. A PCNL was more likely to be offered by urologists trained after 1980
      (100%) than by urologists trained before 1980 (81%; P=0.004). For a large lower
      pole calculus with unfavorable anatomy, urologists with >50% managed-care
      practices were more likely (91%) than urologists with <50% managed-care practices
      (65%) to select PCNL for such stones (P=0.034). Whereas 82% of metropolitan
      urologists would select PCNL, 43% of rural urologists would consider SWL as
      initial therapy. A URS was more likely to be offered by urologists trained after
      1980 (16%) than by urologists trained before 1980 (0; P=0.044). For a large
      proximal-ureteral calculus, metropolitan urologists were most likely (64%) to use
      stents initially (urban 28%; P=0.014; rural 14%; P=0.017). Rural urologists were
      more likely to offer SWL (100%) than were metro urologists (55%; P=0.024).
      CONCLUSIONS: Initial therapy for nephrolithiasis differs significantly according
      to geographic location, year of residency completion, and the percentage of
      managed-care patients in a urologist's practice. Future emphasis should be placed
      on increasing the availability of endoscopic techniques in rural settings.

PMID- 15735383
TI  - Complications of pneumatic ureterolithotripsy in the early postoperative period.
AB  - PURPOSE: To document the perioperative and early postoperative complications of
      pneumatic ureterolithotripsy. PATIENTS AND METHODS: Between January 1997 and
      December 2003, pneumatic ureterolithotripsy was performed in 665 male and 314
      female patients for stones >0.5 cm. The age range was 9 months to 72 years (mean
      41 years). Preoperatively, intravenous urography, urinalysis, and urine culture
      were done. Cefepime 1 g was given as prophylactic antimicrobial therapy 1 hour
      prior to surgery. A plain film of the urinary tract was taken immediately before
      the procedure. The operations were carried out with the patient under general
      anesthesia. Rigid ureteroscopes (6.9F ACMI "micro-6" or 8F-10F Storz) and the
      Vibrolith (Elmed, Ankara, Turkey) pneumatic lithotripter were used. The fragments
      were extracted with forceps or baskets. Urinalysis and culture as a routine
      postoperative evaluation and a plain film or ultrasonogram of the urinary tract
      when needed were done 1 week after the procedure. RESULTS: The stones were
      completely removed in 847 patients (86.5%); 783 (80%) of them went home on the
      day of surgery. A ureteral stent was needed in 401 patients (41.0%).
      Perioperative complications were migration of the stone into the kidney in 70
      patients (7.2%), mucosal damage in 34 (3.5%), ureteral perforation in 17 (1.7%),
      ureteral avulsion in 4 (0.4%), and conversion to open surgery in 3 (0.2%). During
      the early postoperative period, flank pain (18.4%), pelvic discomfort (5.5%),
      macroscopic hematuria (7.3%), and urinary tract infection (5%) were recorded.
      CONCLUSION: Ureterolithotripsy by a pneumatic lithotripter is a minimally
      invasive, highly tolerable procedure with a low complication rate and short
      hospital stay when performed meticulously with appropriate instruments.

PMID- 15735384
TI  - Percutaneous antegrade removal of impacted upper-ureteral calculi: still the
      treatment of choice in developing countries.
AB  - PURPOSE: To assess the safety and efficacy of antegrade percutaneous
      nephrolithotomy (PCNL) of large impacted proximal-ureteral calculi. PATIENTS AND
      METHODS: Between July 1998 and October 2003, a total of 66 patients (43 male and
      23 female; mean age 37.5 years) underwent PCNL for impacted proximal-ureteral
      calculi. The inclusion criteria were calculi >15 mm that were densely impacted
      and located between the ureteropelvic junction and the lower border of the 4th
      lumbar vertebra. The mean drop in hemoglobin, operating time, analgesic
      requirement, and hospital stay were assessed. RESULTS: Sixty-five patients
      (98.5%) had complete calculus clearance in a single session through a single
      tract. The mean operating time and hospital stay were 47 minutes and 46 hours,
      respectively. The mean analgesic requirement was 65 mg of pethidine (meperidine).
      The mean follow-up was 14 months. There were no significant postoperative
      complications. CONCLUSION: Antegrade PCNL is a safe and effective option for
      large, impacted proximal-ureteral calculi.

PMID- 15735385
TI  - Comparison of hand-assisted laparoscopic and open donor nephrectomy: a single
      center experience from South Korea.
AB  - PURPOSE: We report our experience with hand-assisted laparoscopic donor
      nephrectomy (HALDN) and compare to our results with conventional open donor
      nephrectomy (ODN). PATIENTS AND METHODS: From February 2000 to January 2003, 100
      patients (M:F 54:46) underwent HALDN at the Kangnam St. Mary's hospital. These
      patients were divided into early (1st 50 cases) and late (2nd 50 cases) groups.
      These cohorts were compared with 40 patients (M:F 26:14) who underwent ODN via a
      flank incision from January 1999 to January 2003 at the same institution. Patient
      data were obtained from medical record review and personal and telephone
      interviews. RESULTS: The HALDN was completed successfully in 99 donors. The mean
      operative times (minutes) were 225 (140-425), 178 (135-250), and 188 (140-260) in
      the early HALDN, late HALDN, and ODN groups, respectively (P<0.05). The mean warm
      ischemia times (seconds) of the ODN (135+/-52.4) and late HALDN (150+/-76.7)
      groups were shorter than that of the early HALDN group (207+/-88.5) (P<0.05). On
      average, a regular diet was resumed after 2.1, 1.89, and 2.05 days, respectively.
      (P<0.05), and patients were discharged home 4.12, 4.04, and 6.8 days (P<0.05)
      after surgery in the early HALDN, late HALDN, and ODN groups. Analgesic use was
      significantly reduced in the HALDN group in comparison with ODN (P<0.05).
      Complications consisted of two cases of chyloperitoneum and one case each of open
      conversion, transfusion, prolonged ileus, liver enzyme elevation, and recipient
      ureteral necrosis in the early HALDN group; one case of subcutaneous emphysema in
      the late HALDN group; and one case each of transfusion and liver enzyme elevation
      in the ODN group. The mean donor (1 and 30 days) and recipient (6 months) serum
      creatinine concentrations did not differ among the groups (P>0.05). CONCLUSIONS:
      The HALDN appears to be a safe, technically feasible, and effective alternative
      to conventional ODN. The procedure may offer several advantages over conventional
      ODN in terms of less postoperative pain, shorter convalescence, and minimal
      cosmetic disfigurement. The recipient graft function is similar to that after
      ODN.

PMID- 15735386
TI  - Stent-change therapy in advanced malignancies with ureteral obstruction.
AB  - BACKGROUND AND PURPOSE: To determine if patients with advanced malignancies and
      resultant ureteral obstruction who are managed with chronic ureteral stent
      changes have adequate preservation of renal function and an acceptable rate of
      complications. PATIENTS AND METHODS: A retrospective review was conducted on 28
      patients who had a stent to relieve ureteral obstruction caused by cancer.
      RESULTS: During the study period, 201 stents were placed, a median of 4 (range 1
      34) per patient. The mean time from cancer diagnosis to first stent placement was
      34 months (range 1-109 months). The median survival after the first stent
      insertion was 15.3 months (95% CI 15.1, 15.6). Seven patients had worsening renal
      function and hydronephrosis despite indwelling stents. In these patients, the
      median time from the first stent to a rising serum creatinine concentration was
      17 months (range 1-66 months). No patient required dialysis. Eighteen patients
      developed a total of 69 urinary tract infections (mean 2.5). Eight patients had a
      total of 13 episodes of urosepsis. The median infection-free survival was 11.9
      months (range 7.7-16.9 months). The median urosepsis-free survival was 28.5
      months (range 9.7-47.1 months). Fourteen patients died from their malignancies
      during the study. CONCLUSIONS: Stent-change therapy is an efficacious way to
      treat patients with advanced malignancies and ureteral obstruction, many of whom
      have a short life expectancy. All patients maintained adequate renal function to
      obviate dialysis. Most patients with stents in place will die before their renal
      function deteriorates. They may also benefit from treatment strategies designed
      to avoid the occurrence of frequent urinary infections.

PMID- 15735387
TI  - Percutaneous rheolytic thrombectomy for treatment of acute renal-artery
      thrombosis.
AB  - PURPOSE: We present our experience with percutaneous rheolytic treatment with the
      AngioJet thrombectomy catheter for acute renal-artery thrombosis. CASE REPORT: A
      63-year-old male patient with renal-artery thrombosis presented 48 hours after
      the onset of acute nonradiating flank pain. Thrombosis was documented by CT
      angiography, 99mTc-DTPA, and digital subtraction angiography. A percutaneous
      thrombectomy was performed with the AngioJet catheter. At the end of the
      procedure, the arterial lumen was patent, and no underlying stenosis or other
      deformity of the arterial wall was found. Thus, the cause of the obstruction was
      considered to be an embolus. After the procedure, urokinase was given to prevent
      distal occlusions from emboli that could have escaped mechanical thrombectomy.
      Heparin was also administered. The patient was released from the hospital with a
      patent renal unit and ameliorated serum creatinine concentration. CONCLUSION: We
      propose the use of the AngioJet thrombectomy catheter for the percutaneous
      treatment of acute renal-artery thrombosis.

PMID- 15735388
TI  - Feedback microwave thermotherapy with the ProstaLund Compact Device for
      obstructive benign prostatic hyperplasia: 12-month response rates and
      complications.
AB  - PURPOSE: To evaluate the effectiveness of the ProstaLund Compact Device in the
      treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A series
      of 38 consecutive patients with a mean age of 72.6+/-8.2 years, 19 with an
      indwelling catheter, underwent transurethral microwave thermotherapy (TUMT) with
      the ProstaLund Compact Device. Pretreatment evaluation included transrectal
      ultrasonography (TRUS), urodynamics, and cystoscopy for all patients and flow
      rate (Qmax), postvoiding residual urine volume (PVR), International Prostate
      Symptom Score (IPSS), and quality-of-life (QoL) assessment for those without a
      catheter. The mean prostate volume was 63.5+/-30 cc. The Qmax, IPSS, and QoL
      studies were repeated at 3, 6, and 12 months, while urodynamics, cystoscopy, and
      TRUS were repeated at 6 and 12 months. RESULTS: The treatment lasted a mean of
      43.1+/-17.1 minutes, achieved a maximal intraprostatic temperature of 58.7+/-7.2
      degrees C, and destroyed 18.4+/-14.3 g of prostatic tissue. Twelve months post
      treatment, for the patients without a catheter preoperatively, the IPSS was
      improved from 21.5+/-6.3 to 6.5+/-3.1 (P<0.001), Qmax from 7.2+/-3.1 mL/sec to
      18.1+/-7.4 mL/sec (P<0.001), detrusor pressure at Qmax from 87.5+/-15 cm H2O to
      48.4+/-16.4 cm H2O (P<0.001), and PVR from 113.2+/-78.2 mL to 34.6+/-36.7 mL
      (P<0.01). The good-response rates for IPSS (<or=7 or >or=50% improvement), Qmax
      (>or=15 mL/sec or >or=50% improvement), PVR (<50 mL or >or=50% decrease), and QoL
      (<or=2) were 73.7%, 84.2%, 73.7%, and 94.7%, respectively. For the patients with
      a catheter preoperatively, the IPSS improved from 9.5+/-6 at 3 months to 5.1+/
      5.3 (P<0.05) at the end of the follow-up period. The Qmax was 13.2+/-6.4 mL/sec
      at 3 months and remained stable throughout the follow-up period. Patient good
      response rates for IPSS (<or=7), PVR (<150 mL), and QoL (<or=2) were 75%, 87.5%
      and 75%, respectively. Only two patients were unable to void after the treatment.
      Complications were similar to those presented in the literature, and bladder
      stone formation was noted as well (five patients). CONCLUSIONS: ProstaLund
      thermotherapy is a highly promising alternative treatment for BPH, improving
      substantially both objective and subjective measures of bladder outflow
      obstruction.

PMID- 15735389
TI  - Transurethral electrovaporization of the prostate: is it any better than standard
      transurethral prostatectomy? 5-year follow-up.
AB  - BACKGROUND AND PURPOSE: At present, transurethral resection of the prostate
      (TURP) is regarded as the most effective treatment for benign prostate
      hyperplasia (BPH). In the present randomized study, we compared TURP with
      transurethral electrovaporization of the prostate (TUVP). PATIENTS AND METHODS: A
      series of 77 BPH patients who underwent operation between 1996 and 2001 were
      included in the study, 40 who had TURP with a standard resection loop and 32 who
      had TUVP with a Spike loop. All available patients were evaluated preoperatively,
      at 1 month and 3 months after the operation (N=73), and 5 years after the
      operation (N=44). The International Prostate Symptom Score (IPSS), sexual
      function questionnaire, uroflowmetry (Qmax), postvoiding residual urine volume
      (PVR), and transrectal ultrasonography were used. In addition, postoperative
      serum sodium concentration, serum hematocrit, duration of catheterization, and
      operation time were compared. RESULTS: In the TUVP group, the mean IPSS decreased
      from 17.3 to 6.5, the PVR from 88 to 35 mL, and the prostate volume from 39 to 24
      cc, while the Qmax increased from 6.3 to 12.9 mL/sec and the average flow from
      2.6 to 7.9 mL/sec. In the TURP group, the mean IPSS decreased from 17.6 to 6.1,
      the PVR from 95 to 38 mL, and the prostate volume from 38 to 23 cc, while the
      Qmax increased from 5.9 to 13.2 mL/sec and the average flow from 2.4 to 8.3
      mL/sec. Thus, significant improvements were observed in both groups, and the
      differences between them 5 years later were not significant P>0.05).
      Postoperative serum hemoglobin and hematocrit were significantly lower in the
      TURP group (P>0.05). However, no difference was seen in serum sodium
      concentrations. Also, there was no difference in the duration of the operations.
      The catheterization period was 22+/-5.7 hours in the TUVP group, while it was
      75.7+/-10.5 hours in the TURP group (P<0.001). When morbidities observed during
      follow-up were evaluated, no significant difference was seen. CONCLUSIONS: The
      TUVP procedure is as effective as TURP with similar morbidity. The advantages of
      TUVP are that the urethral catheter is withdrawn earlier, hospitalization is
      shorter, and bleeding is less. Its disadvantage is that tissue cannot be sampled
      for histologic diagnosis. In our opinion, in order to exploit the advantages of
      this technique, TUVP should be preferred in elderly patients without any
      suspicion of prostate cancer for whom bleeding during operation is a source of
      risk.

PMID- 15735390
TI  - Laser division of encircling sutures to remove retained urethral catheter after
      radical retropubic prostatectomy.
AB  - Inability to remove a urethral catheter after radical retropubic prostatectomy is
      an uncommon complication. We describe removal of a urethral catheter entrapped in
      vesicourethral anastomotic sutures, which was safely performed endoscopically
      using a holmium laser.

PMID- 15735391
TI  - Novel direct-vision renal morcellation with orthopedic rotary shaver-blade
      instrumentation.
AB  - BACKGROUND AND PURPOSE: When small ports are the only entry (and exit) points
      during laparoscopic nephrectomy, one is forced either to make an accommodating
      incision for final renal delivery or to perform renal morcellation. To date,
      morcellation has been performed in a blind manner with a specimen entrapped in a
      nonpenetrable, nonpermeable sac within the peritoneal cavity. Through the use of
      current laparoscopic equipment and a novel rotary shaver-blade system, we studied
      the safety, feasibility, and efficiency of directly observed renal morcellation.
      MATERIALS AND METHODS: Ten porcine renal units with a mean mass of 143 g (range
      92-192 g) were morcellated via a custom 5.5-mmx28-cm Dyonics (Smith & Nephew,
      Andover, MA) rotary shaver blade placed through a standard operative laparoscope
      (ACMI LAP 11-56W). Each kidney was entrapped in a standard 8x10-inch LapSac (Cook
      Urological, Spencer, Indiana), which was placed in a preconfigured abdomen model.
      Morcellation was performed under direct visual guidance with continuous-flow
      irrigation and suction. We then studied the feasibility, safety, technical ease,
      and efficiency of morcellation; the size of the fragments; and entrapment-bag
      integrity with each renal morcellation. RESULTS: The mean time required to
      complete morcellation was 8:02 minutes (range 4:45-14:00 minutes). The
      morcellation efficiency mean was 20.7 g/min (range 12.00-31.41 g/min), with the
      Dyonics EP-1 generator system morcellating most effectively at 2000 rpm in its
      oscillate mode. Of ten random fragments, the mean size was 8.7x4.7 mm. The
      integrity of one LapSac was lost when the bag was not filled to complete
      distention, creating susceptible in folding. CONCLUSION: This novel technique of
      laparoscopic renal delivery provides a feasible, safe, technically simple, and
      efficient means of morcellation. Directly viewed renal morcellation must occur
      with a kidney freely floating within a completely distended entrapment sac in
      order to preserve the integrity of the sac itself. Tissue fragments are large
      enough for pathologic review, which may permit superior oncologic surgical
      margins.

PMID- 15735393
TI  - Effect of antibiotics on Oxalobacter formigenes colonization of human
      gastrointestinal tract.
AB  - BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the
      human gastrointestinal tract that degrades oxalate and reduces its availability
      for absorption. This bacterium is assumed to be antibiotic sensitive, and
      repeated antibiotic therapies could eradicate it. The aim of the present study
      was to determine the differences in the colonization by O. formigenes of
      individuals who had been on antibiotics for at least 5 days at the time of sample
      collection and individuals who had not taken antibiotics for at least 3 months.
      PATIENTS AND METHODS: Stool samples were collected from 80 individuals without
      stone disease (35 with and 45 without antibiotic consumption) and 100 patients
      with stone disease (20 with and 80 without antibiotic consumption). Oxalobacter
      formigenes was detected by a polymerase chain reaction-based method, and the
      presence/absence of O. formigenes was correlated with urinary oxalate
      concentrations. RESULTS: Lower percentages of individuals without stone disease
      and with stone disease who were consuming antibiotics had O. formigenes
      colonization than individuals without antibiotic consumption. Urinary oxalate
      concentrations were higher in the individuals without O. formigenes than in
      colonized individuals. CONCLUSION: Our observations confirm a direct association
      between antibiotic consumption and absence of O. formigenes. Absence of
      intestinal O. formigenes could represent a pathogenic factor in calcium oxalate
      urolithiasis when antibiotics are prescribed generously.

PMID- 15735392
TI  - Shockwave lithotripsy: dose-related effects on renal structure, hemodynamics, and
      tubular function.
AB  - BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) predictably damages renal
      tissue and transiently reduces function in both kidneys. This study characterized
      the effects on renal function of a supraclinical dose of shockwaves (SWs) (8000)
      in porcine kidneys and tested the hypothesis that such excessive treatment would
      intensify and prolong the resulting renal impairment. MATERIALS AND METHODS: Pigs
      aged 6 to 7 weeks were anesthetized and assigned to one of three groups. Groups 1
      (N=8) and 2 (N=6) each received 8000 SWs at 24 kV (Dornier HM3) to the lower-pole
      calix of one kidney. Group 3 (7 pigs) received sham treatment. Renal function was
      monitored for the first 4 hours after SW treatment in Group 1 and for 24 hours in
      Group 2. Plasma renin activity was measured in Groups 2 and 3. RESULTS: The renal
      lesions produced by 8000 SWs comprised 13.8%+/-1.4% of the renal mass. In the 4
      hour protocol, this injury was associated with marked reduction of the glomerular
      filtration rate (GFR), renal plasma flow (RPF), and urinary sodium excretion in
      both kidneys, although fractional sodium excretion was reduced only in the
      shocked kidneys. In the 24-hour protocol, GFR and RPF remained below baseline in
      shocked kidneys at 24 hours. Evidence of progressive ischemic injury was noted in
      shocked tissue at 24 hours after SW treatment. CONCLUSIONS: These findings
      support the hypothesis that the severity of the renal injury caused by SWL is
      related to the number of SWs administered and demonstrate the connection in this
      relation between renal structure and function.

PMID- 15735394
TI  - PlasmaKinetic bipolar vessel sealing: burst pressures and thermal spread in an
      animal model.
AB  - BACKGROUND AND PURPOSE: Laparoscopic bipolar instruments are commonly employed to
      cauterize and divide tissue. A next-generation bipolar device has been developed
      that employs vapor pulse coagulation energy. We assessed the vessel-sealing
      capability of this device and quantified thermal spread during application.
      MATERIALS AND METHODS: Bilateral laparoscopic nephrectomy was performed on six
      common swine >25 kg. Five-millimeter clips and surgical staplers (US Surgical,
      Norwalk, CT) were utilized to perform nephrectomy on one side, while the Gyrus
      PlasmaKinetic bipolar device (Minneapolis, MN) was employed for the contralateral
      nephrectomy. Vessel-sealing capabilities were assessed via burst-pressure
      studies. The extent of thermal spread was measured after tissue fixation and
      hematoxylin and eosin staining. RESULTS: Surgical clips/vascular staplers
      adequately controlled/sealed renal hilar vessels with burst pressures nearing 300
      mm Hg. The Gyrus bipolar device reliably sealed and divided renal arteries <or=5
      mm with burst pressures averaging 291 mm Hg. Renal arteries above this size were
      not consistently sealed, but, with the exception of one technical error, renal
      veins of all sizes (3-12 mm) were reliably controlled (average burst pressure 288
      mm Hg). Histologic evidence of thermal spread extended an average of 3.6 mm from
      the cut edges of arteries and 3.4 mm from the edges of veins. CONCLUSIONS: The
      Gyrus PlasmaKinetic bipolar device is capable of reliably sealing/ dividing
      arteries as large as 6 mm, although we recommend restricting its use to vessels
      no larger than 5 mm in diameter to allow a safety margin. In addition, porcine
      renal veins of all sizes are adequately controlled. These sealed vessels are able
      to withstand pressures approaching 300 mm Hg. Thermal spread affects only the
      area surrounding the divided vessel. Further clinical studies are warranted.

PMID- 15735395
TI  - Association of vitamin D receptor-gene (FokI) polymorphism with calcium oxalate
      nephrolithiasis.
AB  - BACKGROUND AND PURPOSE: Formation of kidney stones is still not understood but is
      hypothesized to be associated with the vitamin D receptor gene (VDR). In order to
      assess the eventual role of VDR start-codon FokI polymorphism in stone formation,
      we evaluated the association between calcium stone disease and this polymorphism
      in a North Indian population. PATIENTS AND METHODS: A control group comprised of
      166 healthy individuals (age range 22-58 years) and a group of 138 patients with
      calcium oxalate stones (age range 21-72 years) were examined. The polymorphism
      was detected using polymerase chain reaction-based restriction analysis. An
      unexcisable length of 265 bp (CC) and two fragments of 169 bp and 96 bp (TT) were
      obtained by FokI restriction digestion. RESULTS: There was a statistically
      significant difference between the control and patient groups (X2 test, P<0.001)
      for the genotype of the VDR FokI start-codon polymorphism. The odds ratio (with
      95% CI) for the C allele in those at risk of stone disease was 1.654 (1.041,
      2.628). The VDR frequency distribution was also statistically significant
      (P<0.001) in case of male sex. The frequency distribution for this genetic
      polymorphism was not statistically different in normocalciuric and hypercalciuric
      stone patients (P=0.355). CONCLUSION: The VDR FokI polymorphism may be a good
      candidate for a marker for calcium oxalate-stone disease. These findings may
      contribute a small piece to the understanding of the pathogenesis of urinary
      calculi.

PMID- 15735399
TI  - Embryonic stem cell derived cardiomyocytes: potential therapeutic applications
      for heart regeneration.

PMID- 15735400
TI  - Heart cell implantation after myocardial infarction.
AB  - In the last 15 years, heart cell implantation to regenerate infarcted myocardium
      has gone from the bench to clinical trial. Several phase I and II controlled
      randomized trials showed the feasibility, the side effects and the potential
      efficacy of cell implantation after myocardial infarction in humans. Preclinical
      experiments investigating the mechanisms of heart function improvement after cell
      implantation showed controversial results regarding implanted cell
      differentiation into cardiomyocytes and highlighted other effects including
      neovascularization and modifications of the extra cellular matrix remodelling.
      Ongoing clinical and experimental studies should pave the way for cell
      implantation to become a therapeutic option to prevent and treat post-myocardial
      infarction congestive heart failure in a near future.

PMID- 15735401
TI  - Mesenchymal stem cells in the infarcted heart.
AB  - A loss of functional cardiomyocytes forms the cellular basis of cardiac
      dysfunction and heart failure. Stem cell based repletion of scarred myocardial
      tissue and regeneration of cardiomyocytes have been proposed as a potential
      treatment of ventricular dysfunction. In this review, we provide an overview of
      recent studies utilizing mesenchymal stem cells in cardiac regeneration and post
      myocardial infarct therapy.

PMID- 15735402
TI  - Bone marrow stem cells in the infarcted heart.
AB  - Conventionally, the heart is perceived as a terminally differentiated organ,
      which is incapable of regeneration. Adult stem cell transplantation is aimed at
      replenishing the myocyte number to compensate for the cardiomyocyte loss during
      the process of cardiomyocyte necrosis following infarction. More recently, the
      focus has been shifted on the use of autologous skeletal myoblasts and bone
      marrow derived stem cells. Here, we have reviewed some interesting aspects of the
      fast emerging field of bone marrow derived stem cell therapy for cardiac repair.

PMID- 15735403
TI  - Skeletal myoblast for cell therapy.
AB  - After a decade of experimental work, skeletal myoblast transplantation has now
      entered the clinical arena as a potentially new means of improving the function
      of the failing heart. Because of the apparent lack of connections between the
      engrafted myoblasts and the host cardiomyocytes, it is likely that the functional
      benefits of myogenic cell transplantation are more related to limitation of
      adverse post-infarction remodelling and/or paracrine effects on recipient tissue
      rather than to a synchronous contribution of the graft to systolic pump function.
      As the initial clinical studies have primarily documented the feasibility of the
      procedure, it is now critical to assess whether the functional benefits observed
      in the laboratory setting translate into meaningful improvements in cardiac
      contractility and ultimate patient outcomes. Only randomised trials will allow us
      to satisfactorily address efficacy. These trials should also clarify the
      potentially pro-arrhythmic risk of myoblast engraftment, which might be related
      to the heterogeneous electrical properties between donor and recipient cells. In
      parallel, additional experimental studies are still warranted to address some key
      issues including the means of optimising post-transplantation myoblast survival,
      the development of less invasive cell transfer delivery technologies, the role of
      myoblast transplantation in non-ischemic heart failure settings and the
      comparative effects of skeletal myoblasts compared with other potential forms of
      cell therapy such as bone marrow-derived and embryonic stem cells.

PMID- 15735404
TI  - Embryonic stem cells: differentiation into cardiomyocytes and potential for heart
      repair and regeneration.
AB  - Many forms of heart disease are associated with the loss of cardiomyocytes both
      via apoptosis or necrosis, and despite the recent identification of resident
      cardiac stem cells, the native capacity for renewal and repair is inadequate.
      Cell transplantation strategies have emerged as a potential therapeutic approach
      for repairing injured myocardium. Many different cell types including embryonic
      stem cells have been transplanted in myocardial infarction (MI) models with
      resulting improvement in myocardial function. Here, we review the current state
      of knowledge with regard to the potential of embryonic stem (ES) cells to
      differentiate into cardiomyocytes in the embryonic stem cell derived-embryoid
      body (EB) in vitro system as well as for myocardial regeneration following
      myocardial infarction.

PMID- 15735406
TI  - Feasibility and safety of regional myocardial hypothermia during myocardial
      ischemia and infarction in pigs.
AB  - OBJECTIVE: Mild systemic hypothermia has been shown to be feasible and safe in
      patients during acute myocardial infarction (AMI). Regional myocardial
      hypothermia of the ischemic myocardium only may be more effective in myocardial
      salvage with fewer side effects compared with systemic hypothermia. The purpose
      of this study was to evaluate the feasibility and safety of regional myocardial
      hypothermia in pigs. METHODS: Open-chest pigs with (n=5) or without (n=4)
      myocardial infarction underwent left anterior descending coronary artery (LAD)
      ligation followed by intracoronary infusion of lactated Ringer's solution (at
      room temperature and at 15 degrees C between 20-35 ml/min for 3 min) via the
      central lumen of a specially designed balloon catheter at the time of
      reperfusion. Intramyocardial temperatures via thermocouples at the ischemic zone
      (LAD territory) and non-ischemic zone (circumflex territory) as well as systemic
      temperature were constantly recorded, as were the hemodynamics. Each pig acted as
      its control regarding the myocardial temperature response to both solutions. In
      addition, intracoronary versus intramyocardial temperatures were compared with
      thermocouples in both territories during infusion. RESULTS: There was no
      hemodynamic compromise or arrhythmia seen during the intracoronary infusion of
      either temperature solution. There was a linear relationship between the infusion
      solution temperature and infusion rate versus intramyocardial temperature
      response, with the cooled solution providing 2 degrees C lower temperature and
      faster infusion resulting in lower intramyocardial temperature. There was no
      change in the non-ischemic zone or systemic temperature. On average, 6-8 degrees
      C reduction in tissue temperature, potential target temperature range for
      hypothermic therapy, was achieved in all animals. In addition, intracoronary
      temperature in distal LAD measured by intracoronary thermocouples correlated with
      the intramyocardial temperature (2 degrees C lower temperature in the coronary
      artery). CONCLUSION: It is feasible and safe to achieve regional myocardial
      hypothermia by intracoronary infusion of cooled solution in pigs.

PMID- 15735409
TI  - Cutaneous infection with Mycobacterium tuberculosis: how has this altered with
      the changing epidemiology of tuberculosis?

PMID- 15735405
TI  - Loss of insulin receptor substrate-1 signaling induces the cardiovascular and
      proteo(fibrino)lytic system derangements typical of insulin resistance.
AB  - BACKGROUND: Type 2 diabetes and insulin resistance have been associated with
      several cardiac features including diastolic heart failure, impaired ventricular
      function, perimicrovascular fibrosis and increased expression of plasminogen
      activator inhibitor type-1 (PAI-1) in coronary arterial walls. Insulin receptor
      substrate-1 (IRS-1) is one mediator of insulin signaling. This study was
      performed to determine whether induction of cardiac manifestations typical of
      insulin resistance and increased PAI-1 expression occur developmentally or post
      developmentally as a result of loss of IRS-1-mediated signaling. METHODS: IRS-1
      knockout mice were studied at 20 weeks of age. RESULTS: Compared with control
      mice, the left ventricular (LV) and cardiac mass to body weight ratios were
      increased. Diastolic and systolic LV diameters and decreased fractional
      shortening were indicative of LV dilatation and dysfunction. Coronary
      perimicrovascular fibrosis, an increased coronary arterial wall to lumen ratio,
      increased immunoreactivity of PAI-1 in the tunica media and increased PAI-1 mRNA
      expression were present consistent with constrained mural proteo(fibrino)lysis.
      These cardiac manifestations were similar to those we and others have observed
      previously in insulin-resistant mice without impaired IRS-1-mediated signaling.
      CONCLUSIONS: Loss of IRS-1 signaling is sufficient to induce cardiac
      manifestations typical of insulin resistance including increased coronary
      arterial mural PAI-1 expression. Furthermore, increased PAI-1 expression is not
      dependent on IRS-1 signaling.

PMID- 15735410
TI  - Skin complications of Bacillus Calmette-Guerin immunization.
AB  - PURPOSE OF REVIEW: Bacillus Calmette-Guerin (BCG) vaccination has been performed
      since 1921, and remains the best method of preventing severe infections caused by
      Mycobacterium tuberculosis. Tuberculosis, in its various forms, remains a public
      health problem, and more than 100 countries continue BCG vaccination in an effort
      to control the disease. Since the initiation of BCG vaccination, numerous
      complications have been reported. In this review we will focus on the cutaneous
      complications of BCG vaccination. RECENT FINDINGS: Recent case reports detail the
      development of large keloids, and also of juvenile sarcoidosis after BCG
      vaccination. Adverse outcomes from inadvertent intradermal injection of the
      forearm and from revaccination with BCG have also been reported. Other recently
      described skin complications subsequent to BCG vaccination include lupus
      vulgaris, delayed granuloma formation, cutaneous BCG infection in immune
      disorders, anterior chest wall mass, acute erythroderma with multiple skin
      abscesses, ulceration at the BCG site during Kawasaki disease, fixed drug
      eruption, and cutaneous abscesses following mesotherapy. SUMMARY: BCG vaccination
      will continue to be a key method of preventing severe tuberculosis infections for
      the foreseeable future. The World Health Organization currently recommends BCG
      vaccination for all infants living in tuberculosis endemic areas. As such, it is
      important for health care providers to recognize the routinely anticipated
      cutaneous findings of the vaccination, in addition to complications relating to
      the injection. Subsequent care of these skin complications is of paramount
      importance to the health of these patients.

PMID- 15735411
TI  - The diagnosis of necrotizing fasciitis.
AB  - PURPOSE OF REVIEW: A delay in the diagnosis and appropriate treatment of
      necrotizing fasciitis has clearly been demonstrated to increase mortality.
      However, paucity of specific cutaneous signs makes early recognition extremely
      difficult. This review highlights recent developments in the approaches to the
      diagnosis of necrotizing fasciitis. RECENT FINDINGS: A clinical staging of
      necrotizing fasciitis is proposed to better define the progression of the
      disease. Several clinical subtypes of necrotizing fasciitis have been described
      recently with hyperacute and sub-acute variants. Imaging techniques, such as
      magnetic resonance imaging and frozen section biopsies, have been reported to be
      of value in the early recognition of necrotizing fasciitis. However availability
      and cost limit the routine use of these tests. Several diagnostic adjuncts that
      have been developed recently to help in early recognition will be discussed.
      These include the fasciitis LRINEC (laboratory risk indicator for necrotizing
      fasciitis) score and transcutaneous tissue oxygen saturation monitoring. Some may
      have the potential for widespread application in the assessment of severe soft
      tissue infections. SUMMARY: Delayed recognition, with consequent massive soft
      tissue loss and sepsis, remains a deadly pitfall in the management of necrotizing
      fasciitis. With a better understanding of the clinical manifestations and the
      potential use and limitations of various diagnostic adjuncts available for the
      assessment of equivocal cases of soft tissue infections, it is hoped that a clear
      and logical approach to the diagnosis of necrotizing fasciitis may be developed.

PMID- 15735412
TI  - Immunity in vaginal candidiasis.
AB  - PURPOSE OF REVIEW: Vulvovaginal candidiasis and recurrent vulvovaginal
      candidiasis remain a significant problem in women of child-bearing age. While
      host defense mechanisms against infection are poorly understood, the most recent
      studies continue to challenge dogma relative to anti-Candida immunity at other
      mucosal sites that is normally associated with T helper 1-type CD4 T cells.
      RECENT FINDINGS: Four studies comprise the latest findings in host defense
      against vulvovaginal candidiasis. The first from an animal model provided the
      most definitive data to date for the lack of involvement by systemic or local T
      cell-mediated immunity. The second study confirmed a limited role for antibodies
      in vaginal candidiasis; similar to past studies, systemic and local Candida
      specific antibodies in women with vulvovaginal candidiasis were either similar or
      elevated compared with controls. The third study from a cohort of adolescents
      provided evidence for some form of local protective immunity based on high
      asymptomatic vaginal fungal burden with low incidence rate of vulvovaginal
      candidiasis. This was addressed more specifically through a natural history
      protocol involving an intravaginal challenge with live Candida. Results showed a
      strong correlation between infiltration of polymorphonuclear neutrophils and
      symptomatic vulvovaginal candidiasis, with no evidence of an inflammatory
      response in those protected against infection. SUMMARY: Instead of vulvovaginal
      candidiasis being caused by defective or dysfunctional CD4 T helper 1-type cell
      mediated immune reactivity, data suggest that symptomatic vulvovaginal
      candidiasis is associated with an aggressive response by polymorphonuclear
      neutrophils, whereas protection appears to be innate and noninflammatory. The
      role for innate immunity in both protection against, and promotion of,
      symptomatic vulvovaginal candidiasis is paradigm changing.

PMID- 15735413
TI  - Rhinosporidiosis: what is the cause?
AB  - PURPOSE OF REVIEW: Significant advances in knowledge on rhinosporidiosis and
      Rhinosporidium seeberi were made in 1999, 2000, 2003 and 2004. These advances are
      reviewed on account of the continuing sporadic occurrence of the disease
      universally, and because of the availability of new approaches that could resolve
      persisting enigmas of both the disease and its causative pathogen. RECENT
      FINDINGS: R. seeberi, the pathogen that causes rhinosporidiosis, has been
      definitively classified using molecular biological tools in a new clade - the
      Mesomycetozoea, along with 10 parasitic and saprobic microbes. The controversial
      spherical bodies of the endospores have been shown to comprise both lipid/protein
      nutritive bodies and other spherical bodies that are metabolizing units that
      reduce MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide).
      This indicates the viability of these spherical bodies, provisionally identified
      as the electron dense bodies that have also been shown to contain nucleic acids.
      MTT reduction as an indicator of viability has been used to determine the
      sensitivity of rhinosporidial endospores to biocides, antimicrobial drugs, and to
      specific antibodies. Genetic heterogeneity has been identified in strains from
      humans and animals. Cell-mediated and humoral immune responses have been
      demonstrated in human patients and in mice. Several mechanisms of immune evasion
      by R. seeberi have been identified. SUMMARY: These findings are applicable in
      both clinical and laboratory practice, while the basic advances have implications
      in further work on experimental pathogenicity, the biology of R. seeberi, and on
      the epidemiology and pathogenesis of rhinosporidiosis.

PMID- 15735414
TI  - Podoconiosis: endemic nonfilarial elephantiasis.
AB  - PURPOSE OF REVIEW: Podoconiosis is a noncommunicable disease producing
      lymphoedema of the lower limbs; it affects predominantly barefoot agricultural
      workers in the tropics. Why should this be of interest to a journal of infectious
      disease? For many years this disease has not been widely recognized as distinct
      from lymphatic filariasis and yet it may affect about 10% of populations in
      volcanic tropical highlands. It produces considerable morbidity associated with
      limb lymphoedema, impacting on economically productive age groups. As it does not
      fall into the briefs of infectious or chronic disease initiatives of the World
      Health Organization, it has been difficult to attract funds for research and for
      the development of community management approaches. The aim of this review is to
      describe details of the clinical features, management, epidemiological
      significance and evidence for the underlying aetiology of this poorly understood
      condition. RECENT FINDINGS: A recent comprehensive study in Ethiopia by Destas et
      al. identified a mean zonal prevalence of 5.46% of the population with 64% being
      in the economically productive age group. Otherwise there are no other
      contemporary epidemiological publications in this field. SUMMARY: Podoconiosis is
      thought to be a geochemical disease induced by the absorption of ultrafine silica
      particles from the soil (konia) through the skin of the feet (podos) in
      susceptible individuals, leading to a progressive obliterative endolymphangitis.

PMID- 15735415
TI  - Community-associated methicillin-resistant Staphylococcus aureas: not only a
      cause of skin infections, also a new cause of pneumonia.

PMID- 15735416
TI  - Immunomodulatory effects of antimicrobials in the therapy of respiratory tract
      infections.
AB  - PURPOSE OF REVIEW: Several classes of antibiotics, particularly macrolides and to
      some extent quinolones, exert modulatory effects on inflammatory cells. With a
      growing number of experimental and clinical studies being performed, the
      relevance of the immunomodulatory actions of antibiotics to the therapy of
      respiratory infections is discussed in the light of recent reports. RECENT
      FINDINGS: Antibiotics, particularly macrolides, exert both stimulatory and
      inhibitory effects on leukocytes. These effects seem to be related to the
      activation state of the leukocytes, facilitating bacterial killing as well as the
      resolution of local inflammation. In community-acquired pneumonia, this may
      account for the therapeutic benefit of macrolides, even when bacterial
      eradication is not complete. A variety of effects of macrolides on Pseudomonas
      aeruginosa, including the inhibition of biofilm matrix, contribute with
      immunomodulation to the improvement of respiratory function seen with macrolides
      in cystic fibrosis. SUMMARY: Macrolides can facilitate the killing of
      microorganisms in acute respiratory infections through the stimulation of
      neutrophil activation. On long-term administration, anti-inflammatory, T helper
      type 1 lymphocyte-enhancing and biofilm-thinning actions, among others, make
      macrolides valid therapeutic options in chronic infectious/inflammatory
      disorders, even for infections with microorganisms that are not completely
      eradicated.

PMID- 15735417
TI  - New recommendations for the treatment of tuberculosis.
AB  - PURPOSE OF REVIEW: The aim of this article is to give practicing physicians a
      practical approach to the treatment of latent and active tuberculosis and to
      review newer recommendations and common problems encountered in the treatment of
      patients with tuberculosis. RECENT FINDINGS: Recently published literature
      documents the increased incidence of multidrug resistant strains of Mycobacterium
      tuberculosis, the importance of antituberculosis drug toxicities and drug-drug
      interactions, persistent problems in the correct interpretation of the tuberculin
      skin test and ongoing problems with treatment compliance and treatment
      completion. SUMMARY: This article provides a practical approach to the
      interpretation of the tuberculin skin test, the proper approach to the treatment
      of latent tuberculosis infection, and a structured approach to the treatment of
      presumed or documented active tuberculosis infection. Questions about
      tuberculosis that are often asked of infectious disease and pulmonary specialists
      are addressed in a very practical manner.

PMID- 15735418
TI  - Newer respiratory virus infections: human metapneumovirus, avian influenza virus,
      and human coronaviruses.
AB  - PURPOSE OF REVIEW: Recently, several previously unrecognized respiratory viral
      pathogens have been identified and several influenza A virus subtypes, previously
      known to infect poultry and wild birds, were transmitted to humans. Here we
      review the recent literature on these respiratory viruses. RECENT FINDINGS: Human
      metapneumovirus has now been detected worldwide, causing severe respiratory tract
      illnesses primarily in very young, elderly and immunocompromised individuals.
      Animal models and reverse genetic techniques were designed for human
      metapneumovirus, and the first vaccine candidates have been developed.
      Considerable genetic and antigenic diversity was observed for human
      metapneumovirus, but the implication of this diversity for vaccine development
      and virus epidemiology requires further study. Two previously unrecognized human
      coronaviruses were discovered in 2004 in The Netherlands and Hong Kong. Their
      clinical impact and epidemiology are largely unknown and warrant further
      investigation. Several influenza A virus subtypes were transmitted from birds to
      humans, and these viruses continue to constitute a pandemic threat. The clinical
      symptoms associated with these zoonotic transmissions range from mild respiratory
      illnesses and conjunctivitis to pneumonia and acute respiratory distress
      syndrome, sometimes resulting in death. More basic research into virus ecology
      and evolution and development of effective vaccines and antiviral strategies are
      required to limit the impact of influenza A virus zoonoses and the threat of an
      influenza pandemic. SUMMARY: Previously unknown and emerging respiratory viruses
      are an important threat to human health. Development of virus diagnostic tests,
      antiviral strategies, and vaccines for each of these pathogens is crucial to
      limit their impact.

PMID- 15735420
TI  - Administration of first hospital antibiotics for community-acquired pneumonia:
      does timeliness affect outcomes?
AB  - PURPOSE OF REVIEW: Associations between processes of care for hospitalized
      community-acquired pneumonia patients and clinical outcomes are important because
      of the high incidence of such admissions and substantial related mortality.
      Several studies have examined these associations. RECENT FINDINGS: Large
      retrospective studies of older patients have demonstrated associations between
      time to first dose as short as 4 h and length of stay and mortality during and
      after hospitalization. Results of smaller studies have been less consistent. The
      association appears to be strongest among older patients who have not received
      antibiotics prior to arrival at the hospital. SUMMARY: A significant and causal
      relationship appears to exist between antibiotic timing and improved outcomes,
      especially among older patients. Even modest improvements in timeliness of
      antibiotic administration could impact a substantial number of lives because of
      the high incidence of community-acquired pneumonia hospitalization.

PMID- 15735419
TI  - Nosocomial sinusitis: a unique subset of sinusitis.
AB  - PURPOSE OF REVIEW: Nosocomial sinusitis is a complication of critically ill
      patients that is frequently not considered as a cause of fever and infection.
      While this disease has been described in the literature there have been few
      recent citations on this subject. This brief review will familiarize the reader
      with the current state of the art with regard to diagnosis complications and
      treatment of this problem. RECENT FINDINGS: Nasal and oral tubes have been the
      prime inciting events. Other risk factors have been facial trauma, inability to
      mobilize the patient and prior sinus disease. Patients usually present while in
      the intensive care unit; and there are few signs that suggest sinusitis to the
      critical care team. A number of complications including direct extension to the
      brain, lung and blood stream, as well as sepsis and even death have been
      described. The diagnosis is usually made with the help of specific radiographs or
      computed tomography scans when these modalities are used. The microbiology is
      quite different than sinusitis in the community. Staphylococcus spp., Pseudomonas
      spp. and other nosocomial organisms are frequently isolated when specific
      cultures are obtained. Treatment usually consists of removal of the tubes
      mobilizing the patient and institution of broad-spectrum antibiotics aimed at the
      offending organisms. SUMMARY: Nosocomial sinusitis continues to be a major
      problem causing morbidity and occasionally mortality in critically ill patients.
      Recent findings have suggested that a careful search for this disease and
      appropriate treatment if found can decrease both morbidity, mortality and
      subsequent other nosocomial infections.

PMID- 15735421
TI  - Monotherapy versus combination antimicrobial therapy for pneumococcal pneumonia.
AB  - PURPOSE OF REVIEW: In the past 5 years a number of studies have suggested that
      combination antibiotic therapy may be superior to monotherapy for pneumococcal
      pneumonia. This review outlines the major findings for and against combination
      therapy. RECENT FINDINGS: The evidence for a benefit of multiple antibiotics is
      strongest in patients with severe, bacteremic pneumococcal disease. All of these
      studies have limitations due to their retrospective or uncontrolled design.
      Unfortunately prospective, randomized, double-blind, controlled studies have not
      been performed in an appropriately severe disease cohort and are therefore
      urgently needed. Several viable mechanisms for a benefit of combination therapy
      have been proposed, especially related to non-antibiotic effects of macrolides.
      There is also some evidence that third-generation cephalosporins may be superior
      to penicillins as the non-macrolide component of combination therapy. SUMMARY:
      Although based on retrospective and observational data, there is substantial
      evidence to support combination antibiotic therapy, at least in patients with
      severe bacteremic pneumococcal pneumonia. What evidence is available supports a
      cephalosporin/macrolide combination as being associated with the highest
      survival, but proper prospective studies in patients with severe pneumonia are
      urgently required to clarify this issue.

PMID- 15735422
TI  - Pneumonia associated with HIV infection.
AB  - PURPOSE OF REVIEW: Pneumonia occurs commonly in HIV-infected patients and this
      review highlights some of the recent findings in the epidemiology, pathogenesis,
      clinical features, treatment and prevention of this condition. RECENT FINDINGS:
      Pneumonia remains an important cause of morbidity and mortality in HIV-infected
      patients. A number of factors have been identified that increase the risk of
      pneumonia. Cigarette smoking increases the risk of lung colonization, as well
      acute pneumonia due to Pneumocystis jiroveci, and has been documented to produce
      significant depression of the phagocytic function of alveolar macrophages in HIV
      infected patients, which may underlie this risk. Legionella pneumophila
      infections appear to be uncommon in HIV-infected patients, while pneumonia with
      Streptococcus pneumoniae continues to occur with regularity, including infections
      with antibiotic-resistant isolates. Pneumocystis pneumonia occurs with a low
      incidence in patients receiving HAART, once the CD4 count increases to over 200
      microl. Studies of invasive pneumococcal infections (predominantly pneumonia)
      indicate that in critically ill cases, including HIV-seropositive patients,
      combination antibiotic therapy is associated with a lower mortality than
      monotherapy. The 23-polyvalent pneumococcal vaccine has been shown to reduce the
      risk of pneumococcal infection in HIV-infected adults receiving HAART, and a 9
      valent conjugate pneumococcal vaccine has been shown to reduce the incidence of
      radiologically confirmed pneumonia in HIV-seropositive and HIV-seronegative
      children. SUMMARY: Pneumonia remains an important condition in HIV-infected
      patients, but recent studies demonstrate that antibiotic prophylaxis, the
      introduction of HAART, recognition of specific risk factors, new antibiotic
      treatment strategies and effective vaccines should serve to decrease its impact.

PMID- 15735423
TI  - Bibliography. Current world literature. Skin and soft tissue infections.

PMID- 15735427
TI  - Infliximab efficacy in pediatric ulcerative colitis.
AB  - BACKGROUND: The effects of infliximab, a tumor necrosis factor-alpha (TNF-alpha)
      antibody, have been well established in adult patients with inflammatory and
      fistulizing Crohn's disease. This study evaluates short- and long-term efficacy
      of infliximab in children with ulcerative colitis. METHODS: All pediatric
      patients with ulcerative colitis who received infliximab between July 2001 and
      November 2003 at the Johns Hopkins Children's Center were identified. Short- and
      long-term outcomes and adverse reactions were evaluated. RESULTS: Twelve
      pediatric patients with ulcerative colitis received infliximab for treatment of
      fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid
      dependent colitis (5), and steroid-refractory colitis (1). Nine patients had a
      complete short-term response, and 3 had partial improvement. The mean per patient
      dose of corticosteroid after the first infliximab infusion decreased from 45
      mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day
      at 8 weeks (P = 0.008). Eight patients were classified as long-term responders
      with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3
      underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long
      term nonresponders were steroid-refractory compared with 1 of 8 long-term
      responders. Patients receiving 6-mercaptopurine had a better response to
      infliximab. CONCLUSION: Infliximab should be considered in the treatment of
      children with symptoms of acute moderate to severe ulcerative colitis.

PMID- 15735428
TI  - Anti-inflammatory role of interleukin-15 in Crohn's disease.
AB  - BACKGROUND: Interleukin (IL)-15 is overexpressed in intestinal tissue with active
      Crohn's disease (CD). However, its role in the pathogenesis of the disease
      remains uncertain. We studied the effects of IL-15 on colonic mucosal
      proinflammatory cytokine response in vitro using organ culture of human colonic
      explants. METHODS: Colonic tissue was obtained from (1) resections in pediatric
      CD patients (inflamed and noninflamed) and (2) rectal biopsies in patients with
      CD undergoing colonoscopy (n = 31) and controls (n = 9). In preliminary
      experiments, explants from the resections were cultured in the presence or
      absence of a simulated T(H)1 stimulation using ionomycin (Io) and phorbol
      myristate-acetate (PMA), with or without IL-15, or in medium alone. Rectal
      biopsies were cultured in the same conditions as above, with or without adding a
      monoclonal anti-IL-15 neutralizing antibody (mAb). Levels of interferon (IFN)
      gamma, tumor necrosis factor (TNF)-alpha, and IL-2R alpha were measured by enzyme
      linked immunosorbent assay. RESULTS: IL-15, in the absence of Io + PMA, did not
      induce the expression of IFN-gamma, TNF-alpha, or IL-2R alpha. Only inflamed
      explants from resections stimulated with Io + PMA expressed IFN-gamma, TNF-alpha,
      and IL-2R alpha. This T(H)1 stimulatory effect was inhibited by IL-15 in a dose
      dependent fashion. In rectal biopsy explants, inflamed, noninflamed CD, and
      control tissue responded to stimulation with Io + PMA (P < 0.05) with increased
      IFN-gamma and TNF-alpha (P < 0.05). This response was again inhibited by IL-15.
      The inhibitory effect of IL-15 was specifically reversed by anti-IL-15 mAb (P <
      0.05). The data for the CD group were also analyzed according to the severity of
      colonic inflammation and medication use. CONCLUSIONS: Our results suggest a
      possible anti-inflammatory role for IL-15 in CD. We postulate that its
      overexpression in CD potentially represents a protective mechanism against the
      exaggerated T(H)1 immune response.

PMID- 15735429
TI  - The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays
      the onset of inflammatory bowel disease in mice with interleukin 10 deficiency.
AB  - AIMS: To test whether the peroxisome proliferator-activated receptor gamma
      (PPARgamma) ligand rosiglitazone (Ro) has therapeutic activity in the IL-10(-/-)
      mouse model of inflammatory bowel disease (IBD), and to identify the cellular
      targets and molecular mechanisms of Ro action. METHODS: The progression of
      spontaneous chronic colitis in IL-10(-/-) mice was compared in 5-week-old mice
      fed a standard diet with or without Ro for 12 weeks. The possible therapeutic
      effect of Ro was also tested over a 6-week interval in older IL-10(-/-) mice with
      established IBD. RESULTS: Treatment with Ro slowed the onset of spontaneous IBD
      in IL-10(-/-) mice. Crypt hyperplasia, caused by increased mitotic activity of
      crypt epithelial cells, was also delayed by Ro. Treatment with Ro significantly
      decreased expression of interferon gamma (IFNgamma), interleukin 17 (IL-17),
      tumor necrosis factor alpha, and the inducible nitric oxide synthase mRNA in the
      colon, whereas expression of IL-12p40 was unchanged. PPARgamma was detected in
      epithelial cells throughout the crypts and surface. Ro increased expression of
      PPARgamma protein in these cells, suggesting the existence of a positive feedback
      loop that would potentiate its action in these cells. Ro also specifically
      increased expression of a novel PPAR target, aquaporin-8 (AQP8), in
      differentiated colonic epithelial surface cells, demonstrating that PPARgamma is
      not only present but also regulates gene expression in these cells in vivo.
      Finally, Ro was ineffective in improving disease activity in older IL-10(-/-)
      mice with established IBD. CONCLUSIONS: PPARgamma is expressed, and the PPARgamma
      ligand Ro regulates gene expression in colonic epithelial cells. As a single
      agent, Ro works best for disease prevention in the IL-10(-/-) mouse model for
      IBD.

PMID- 15735430
TI  - Intestinal antiinflammatory effects of thiazolidenedione peroxisome proliferator
      activated receptor-gamma ligands on T helper type 1 chemokine regulation include
      nontranscriptional control mechanisms.
AB  - Crohn's disease is associated with an excessive T helper (TH) type 1 inflammatory
      immune response. Reducing the influx of disease-associated CD4+ TH1 cells into
      the inflamed intestine is likely to be beneficial in preventing a disease flare
      up and even possibly in reducing the effect of acute disease. Thiazolidenedione
      (TZD) ligands, which activate peroxisome proliferator-activated receptor-gamma
      (PPARgamma), have been shown to reduce TH1 inflammation in murine models of
      colitis, primarily in a preventative fashion. To determine whether PPARgamma
      ligands reduce this inflammation in part by reducing TH1 chemoattractant levels
      in vivo, the TZD pioglitazone was tested for its effects on a TH1 chemokine
      (CXCL10) in 2 models of colitis (i.e., dextran sodium sulfate and 2,4,6
      dinitrobenzene sulfonic acid-mediated colitis). In both models, CXCL10 levels
      were significantly reduced by pioglitazone. Because TZDs can affect gene
      expression either directly, by regulating the binding of PPARgamma to consensus
      promoter elements, or indirectly, by modulating other signaling pathways that can
      affect gene transcription, the regulation of CXCL10 by TZDs was investigated in
      vitro in both HT-29 colon epithelial cells and THP-1 monocyte/macrophage cells.
      TZDs significantly reduced CXCL10 protein levels from activated HT-29 cells and
      THP-1-derived macrophages in a dose-dependent manner at nanomolar concentrations.
      However, TZDs did not affect messenger RNA levels or nuclear factor-kappaB
      activation at these concentrations in these cells. These findings imply the
      existence of a novel posttranscriptional regulatory antiinflammatory mechanism by
      TZDs that is not associated with reductions in nuclear factor-kappaB activation.

PMID- 15735431
TI  - Comparative analysis of the in vitro prosecretory effects of balsalazide,
      sulfasalazine, olsalazine, and mesalamine in rabbit distal ileum.
AB  - BACKGROUND: The aminosalicylates remain foundation therapy for mild-to-moderate
      ulcerative colitis. Pro-drug 5-aminosalicylic acid (5-ASA; mesalamine)
      formulations have been developed to prevent 5-ASA from the proximal absorption
      and release of mesalamine, to decrease inflammation, and to improve colonic
      absorption. Clinically, pro-drugs such as olsalazine have been associated with
      dose-dependent diarrhea, which was likely secondary to ileal secretion induced by
      the azo linkages, in 17% of patients. The present study tested the hypothesis
      that the use of all compounds with azo linkages leads to increased secretion.
      METHODS: Intestinal tissue was randomly assigned to serve as controls or to
      receive brush border addition of equimolar concentrations of the compounds, and
      the change in short-circuit current was measured. RESULTS: Mesalamine did not
      induce secretion at any dose. Mean equivalent doses (0.1 to 10 mM) of balsalazide
      (range, 6.3 +/- 1.5 to 16.7 +/- 1.3 microA/cm2), olsalazine (range, 2.0 +/- 1.0
      to 7.0 +/- 2.1 microA/cm2), and sulfasalazine (3.2 +/- 1.1 to 6.2 +/- 1.5
      microA/cm2) significantly stimulated (P < 0.001) secretion. The values for the
      effective dose that is half the maximal dose for secretion induced by
      sulfasalazine, olsalazine, and balsalazide were 0.4, 0.7, and 0.9 mM,
      respectively. CONCLUSIONS: This study is the first to demonstrate that the use of
      pro-drugs with azo bonds leads to increased ileal secretion at equimolar
      concentrations of 5-ASA. Physicians should use caution when providing higher
      doses of the pro-drug forms of 5-ASA to their patients, as this could lead to
      increased diarrhea.

PMID- 15735432
TI  - MAdCAM-1 expression and regulation in murine colonic endothelial cells in vitro.
AB  - BACKGROUND: Although the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is
      associated with the etiology of inflammatory bowel diseases, few studies have
      directly examined MAdCAM-1 using microvascular endothelium derived from the
      colon. This study measured the expression of MAdCAM-1 in a novel colon
      endothelial line MJC-1, as well as MAdCAM-1 regulation and function in vitro.
      METHODS: We cloned microvascular endothelial cells from primary colon cultures
      using ImmortoMice mice (whose cells express a temperature-sensitive SV40 large T
      antigen, H-2Kb-tsA58 mice). Expression of MAdCAM-1 after stimulation with
      cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, or
      interferon (IFN)-gamma] was determined by Western blotting. Signal paths
      regulating MAdCAM-1 expression were examined using pharmacological blockers
      before cytokines. We also examined lymphocyte adhesion using lymphocytes that
      constitutively express alpha4beta7 integrin. RESULTS: TNF-alpha induced MAdCAM-1
      in a dose-dependent manner by 24 hours. MAdCAM-1 induction was protein kinase C,
      tyrosine kinase, p38 mitogen activated protein kinase, and nuclear-factor kappa
      B/poly adenosine diphosphate ribose polymerase dependent. Lymphocyte adhesion was
      increased 2.6-fold after TNF-alpha stimulation and was inhibited by anti-MAdCAM-1
      antibody before treatment (P < 0.05 control versus TNF-alpha). CONCLUSIONS: In
      vitro, MAdCAM-1 can be induced on colon endothelial cells by TNF-alpha
      stimulation and may represent a useful model to study microvascular injury in the
      large intestine.

PMID- 15735433
TI  - Preventative effects of lactulose in the trinitrobenzenesulphonic acid model of
      rat colitis.
AB  - AIMS: Lactulose is a drug used as a laxative that has been shown to promote the
      growth of lactobacilli and bifidobacteria, acting as a prebiotic and with a
      potential beneficial effect in inflammatory bowel disease. The present study
      describes the preventive antiinflammatory activity of lactulose in the
      trinitrobenzenesulphonic acid (TNBS) model of rat colitis. METHODS: Rats were
      rendered colitic by a colonic instillation of 10 mg of TNBS dissolved in 0.25 mL
      of 50% ethanol. One group of colitic rats received lactulose, which was
      incorporated in the drinking water (2.5% wt/vol) for 2 weeks before TNBS
      instillation, and colonic damage was evaluated 1 week after colitis induction.
      Different biochemical markers of colonic inflammation were assayed:
      myeloperoxidase activity, glutathione content, tumor necrosis factor alpha,
      leukotriene B4 levels, and colonic inducible nitric oxide synthase expression. In
      addition, bacterial counts (for lactobacilli and bifidobacteria) were performed
      in colonic contents from colitic rats. RESULTS: The results show that lactulose
      exerted a preventive antiinflammatory effect in this model of rat colitis, as
      evidenced by a significant reduction of myeloperoxidase activity and by a
      decrease of both colonic tumor necrosis factor alpha and leukotriene B4
      production. This effect was also characterized by an inhibition of colonic
      inducible nitric oxide synthase expression, which is unregulated as a consequence
      of the inflammatory status. This beneficial effect was associated with increased
      levels of lactobacilli and bifidobacteria species in colonic contents in
      comparison with untreated colitic rats. CONCLUSION: In conclusion, the intestinal
      antiinflammatory effect of lactulose could be related to its prebiotic
      properties, supporting its potential use in human inflammatory bowel disease.

PMID- 15735434
TI  - Determinants of life satisfaction in inflammatory bowel disease.
AB  - In patients with Crohn's disease (CD) and ulcerative colitis (UC), medical,
      sociodemographic, and psychologic "risk and protective" factors for general and
      health-related life satisfaction (GLS and HRLS, respectively)--defined as
      preference-based judgments of general and health-related quality of life--have
      not been studied to date. METHODS: A total of 429 of 868 (49%) outpatients (CD, n
      = 317; UC, n = 112) attending 3 tertiary care centers and members of the German
      Crohn's Disease/Ulcerative Colitis Foundation completed the sociodemographic and
      medical questionnaires of the German "Competence Network Inflammatory Bowel
      Diseases," the Hospital Anxiety and Depression Scale, and the "Questions on Life
      Satisfaction(Modules)". Disease activity was assessed by the German Inflammatory
      Bowel Disease Activity Index. "Questions on Life Satisfaction(Modules)" data were
      compared with a representative sample of the German general population. RESULTS:
      GLS and HRLS were reduced compared with the general German population (P <
      0.005). Logistic regression showed that mental disorder was a risk factor of
      reduced GLS in CD [odds-ratio (OR), 2.7; P < 0.01] and UC (OR, 6.3; P < 0.02).
      Membership in a self-help organization offered no protection against reduced GLS
      in CD (OR, 0.5; P < 0.02). In CD, psychiatric (OR, 10.4; P < 0.01) and medical
      comorbidity (OR, 2.0; P < 0.02) and disease activity (OR, 4.0; P < 0.01) were
      risk factors of reduced HRLS, whereas in UC, only disease activity (OR, 6.6; P <
      0.01) predicted reduced HRLS. CONCLUSIONS: To improve GLS and HRLS in
      inflammatory bowel disease, both the treatment of bowel disease and medical and
      psychiatric comorbidity are necessary. Strengthening of social support is an
      additional way to promote GLS.

PMID- 15735435
TI  - Amount of systemic steroid medication is a strong predictor for the use of
      complementary and alternative medicine in patients with inflammatory bowel
      disease: results from a German national survey.
AB  - OBJECTIVES: Previous studies have suggested that inflammatory bowel disease (IBD)
      patients rank high among users of complementary and alternative medicine (CAM).
      To further elucidate this phenomenon, we sent questionnaires to a large sample of
      IBD patients in Germany to determine the patterns and predictors of their CAM
      use. METHODS: Pretested 73-item questionnaires were mailed to a randomly selected
      representative sample of 1000 IBD patients from the approximately 16,000 members
      and associates of the German Crohn's and Colitis Association. Predictors of CAM
      use were evaluated by logistic regression models. RESULTS: Completed
      questionnaires were returned by 684 patients (female patients, 61.4%; Crohn's
      disease patients, 58.3%; ulcerative colitis patients, 38.2%). Of the 671 adult
      respondents, 344 (51.3%) had experience with CAM, and significantly more of the
      ulcerative colitis patients (59.8%) than the Crohn's disease patients (48.3%) had
      experience with CAM. There was no difference by gender. Homeopathy (52.9%) and
      herbal medicine (43.6%) were the most commonly used types of CAM. The most
      frequent personal reasons for CAM use were the search for an "optimum treatment"
      (78.9%) and the wish to stop taking steroids (63.8%). Using logistic regression,
      we found that total cortisone intake (P = 0.0077), but not duration of disease,
      was a strong predictor of CAM use. Other predictors were experience with
      psychosomatic and psychotherapeutic support (P = 0.0029), relaxation techniques
      (P = 0.0284), an academic education (P = 0.0173), a diet utilizing whole grains
      (P = 0.0123), and a normal body weight (P = 0.0215). Although 80% of patients
      indicated that they were interested in using CAM in the future, only 24.7% felt
      sufficiently informed about it. CONCLUSIONS: More than 50% of a large group of
      German IBD patients had used CAM. Prolonged or intensive steroid treatment, an
      academic education, active ways of coping, and a health-conscious life-style are
      associated with CAM use. Given the potential side effects and interactions, the
      treating physician should focus on thorough information about the benefits and
      limitations of conventional and complementary treatment options, especially for
      IBD patients who have received prolonged or intensive steroid treatment.

PMID- 15735436
TI  - Muscle performance in patients with Crohn's disease in clinical remission.
AB  - BACKGROUND: Because patients with Crohn's disease (CD) often show increased
      energy expenditure, nutritional deficiencies, and general fatigue, all which may
      persist after a flare, we hypothesized that CD could alter muscle mass and
      function. This study aimed to assess muscle strength and endurance in CD patients
      in clinical remission and the influencing factors. METHODS: Forty-one outpatients
      (17 men and 24 women; age, 37 +/- 10 yr), in remission (CD Activity Index < 150)
      for > 3 months, and 25 age-matched healthy controls (10 men and 15 women; age, 37
      +/- 13 yr) were evaluated. Evaluation included a sit-up test, hand-grip strength
      test, hand-grip endurance test, lower limb strength test, and lower limb
      endurance test (LE), as well as a measure of physical activity. RESULTS: No
      significant difference was found between CD and control groups regarding weight,
      height, body mass index, fat mass, and fat-free mass. Strength performance was
      lower in CD subjects compared with controls, particularly for lower limb indexes:
      lower limb strength test (-24.6%, P < 0.001), LE (-25.8%, P < 0.001), and sit-up
      test (-25.1%, P < 0.001). Previous disease severity, disease duration, the
      cumulative dose of glucocorticosteroids, current inflammation, and global
      habitual physical activity did not affect muscle performance. A recent use of
      steroids improved LE. CONCLUSIONS: CD patients in clinical remission have
      decreased muscle function that may affect their quality of life. This pattern is
      reflected by reduced strength and endurance indexes, particularly for lower
      limbs. The reasons for these changes need further study. Strength training should
      be assessed in these patients.

PMID- 15735437
TI  - The vasculature and inflammatory bowel disease: contribution to pathogenesis and
      clinical pathology.

PMID- 15735438
TI  - Consensus conference: Colorectal cancer screening and surveillance in
      inflammatory bowel disease.
AB  - The idiopathic inflammatory bowel diseases, ulcerative colitis and Crohn's
      colitis, are associated with an increased risk for developing colorectal cancer.
      To reduce colorectal cancer mortality in inflammatory bowel disease, most
      patients and their physicians choose to follow a program of surveillance
      colonoscopy in an attempt to detect early neoplastic lesions at a curable stage.
      Colectomy is typically reserved for patients whose biopsy findings are indicative
      of heightened cancer risk based on interpretation by pathologists. Despite the
      absence of prospective controlled clinical trials to formally evaluate the
      benefits, risks, and costs of this approach, enough circumstantial evidence has
      accrued to warrant its widespread adoption in practice. Nevertheless, no
      standardized guidelines have yet been set forth to guide the gastroenterologist
      in performing surveillance. A panel of international experts was assembled to
      develop consensus recommendations for the performance of surveillance. The
      findings are presented herein.

PMID- 15735439
TI  - What does football have in common with Crohn's disease? The best "defense-in" is
      a good offense.

PMID- 15735440
TI  - HIV epidemics driven by late disease stage transmission.
AB  - How infectious a person is when infected with HIV depends on what stage of the
      disease the person is in. We use 3 stages, which we call primary, asymptomatic,
      and symptomatic. It is important to have a systematic method for computing all 3
      infectivities so that the measurements are comparable. Using robust modeling, we
      provide high-resolution estimates of semen infectivity by HIV disease stage. We
      find that the infectivity of the symptomatic stage is far higher, hence more
      potent, than the values that prior studies have used when modeling HIV
      transmission dynamics. The stage infectivity rates for semen are 0.024, 0.002,
      and 0.299 for the primary, asymptomatic, and symptomatic stages, respectively.
      Implications of our infectivity estimates and modeling for understanding
      heterosexual epidemics such as that in sub-Saharan African are explored.

PMID- 15735441
TI  - Depletion in antibodies targeted to the HR2 region of HIV-1 glycoprotein gp41 in
      sera of HIV-1-seropositive patients treated with T20.
AB  - The anti-HIV drug T20 is a synthetic peptide derived from the HR2 region of HIV-1
      gp41. T20 contains the sequence ELDKWA, which binds the broadly neutralizing
      antibody 2F5. Using plates coated with T20 or with synthetic peptides and
      recombinant proteins representing gp120 or gp41 domains, this study investigated
      by enzyme-linked immunosorbent assay the levels of antibodies directed to the
      gp160 molecule in patients treated with T20. Analysis of sera obtained before and
      after administration of T20 indicated that the levels of antibodies directed to
      T20, to MBP44, a maltose binding protein representing the HR2 region, and to
      4765, a synthetic peptide containing the sequence ELDKWA, fell following
      administration of T20, while the levels of antibodies directed to other regions
      of gp41 ectodomain and to gp120 remained stable. The decline observed was
      independent of the viral load and of the total IgG concentration. Follow-up
      studies with sera obtained from HIV-1-seropositive patients naive to T20
      indicated no decline in the level of antibodies directed to HR2 and other regions
      of gp160. Analysis of sera obtained from a patient after 2 months of T20
      treatment interruption showed a level of antibodies to the HR2 region similar to
      that measured before administration of T20. The addition of increasing amounts of
      T20 to sera from T20-naive patients decreased the level of serum antibodies
      against peptide 4765, T20, and MBP44. The observation of antibody depletion by
      T20 suggests that anti-gp41 antibodies may interfere with T20 treatment by
      forming T20-antibody complexes.

PMID- 15735442
TI  - Increased adipocyte apoptosis in lipoatrophy improves within 48 weeks of
      switching patient therapy from Stavudine to abacavir or zidovudine.
AB  - OBJECTIVES: Lipoatrophy is an important manifestation of the lipodystrophy
      syndrome and is particularly associated with stavudine exposure. Increased
      apoptosis has been suggested as a possible mechanism of lipoatrophy. We assessed
      the degree and reversibility of adipocyte apoptosis in patients with lipoatrophy
      before and 48 weeks after substituting abacavir or zidovudine for stavudine.
      METHODS: Apoptotic adipocytes were identified using terminal transferase dUTP
      nick end labeling and quantified using video image analysis. RESULTS: Fat biopsy
      specimens were obtained from patients before (n = 15) and 48 weeks after (n = 10)
      switching from stavudine and from 20 HIV-uninfected controls. More apoptotic
      cells were seen in fat samples from patients with lipoatrophy treated with
      stavudine than in specimens from controls (P < 0.0001). Forty-eight weeks after
      switching from stavudine to abacavir or zidovudine, there was a reduction in
      apoptotic cells per unit area (P = 0.01) and as a proportion of all adipocytes
      present (P = 0.02) in patient biopsy specimens. Levels of adipocyte apoptosis in
      the 48-week biopsy specimens were no longer significantly different from those
      seen in control biopsy specimens (P > 0.1). CONCLUSIONS: Increased apoptosis is
      present in fat samples from patients with lipoatrophy treated with stavudine.
      This improves toward normal within 48 weeks of switching from stavudine to
      abacavir or zidovudine, suggesting a causative role for stavudine in this
      process.

PMID- 15735443
TI  - Contribution of cellular HIV-1 DNA quantification to the efficacy analysis of
      antiretroviral therapy: a randomized comparison of 2 regimens, including 3 drugs
      from 2 or 3 classes (TRIANON, ANRS 081).
AB  - Cellular HIV-1 DNA level was sequentially measured by quantitative polymerase
      chain reaction in 141 patients not previously treated with highly active
      antiretroviral therapy (HAART), who were enrolled in a 72-week randomized trial
      (ANRS 081 "Trianon") comparing 2 regimens, including 3 drugs from 2 classes
      (indinavir + stavudine + lamivudine, group 1) or 3 classes (indinavir + stavudine
      + nevirapine, group 2). The median decrease from baseline to week 72 in cellular
      HIV-1 DNA level was not significantly different between the 2 groups (0.54 and
      0.45 log10 copies/10 peripheral blood mononuclear cells [PBMCs] in groups 1 and
      2, respectively), whereas a higher proportion of patients maintained a plasma HIV
      1 RNA level less than 20 copies/mL at week 72 in group 1 than in group 2 (79% and
      52%; P = 0.0009). Furthermore, the difference in cellular HIV-1 DNA decrease from
      baseline to week 72 between patients who achieved a plasma HIV-1 RNA level less
      than 20 copies/mL at week 72 and those who did not was not statistically
      significant (0.54 and 0.45 log10 copies/10 PBMCs, respectively; P = 0.14). The
      decay in cellular HIV-1 DNA from baseline to week 72 was higher in antiretroviral
      naive patients than in pretreated patients (0.55 and 0.23 log10 copies/10 PBMCs,
      respectively; P = 0.0008). The cellular HIV-1 DNA level change under therapy was
      best fitted to a 2-phase decay model with a junction point at week 16, from which
      its half-life was estimated at 18 weeks during the initial phase and at 104 weeks
      thereafter. In conclusion, the changes under therapy in cellular HIV-1 DNA level,
      which were mostly coincident to those of plasma HIV-1 RNA, did not add
      significant information to the comparison of the viral efficacy of the 2 studied
      regimens.

PMID- 15735444
TI  - Prescribing of contraindicated protease inhibitor and statin combinations among
      HIV-infected persons.
AB  - HIV-1 protease inhibitors (PIs) contribute to hyperlipidemia in persons treated
      for HIV infection. There are potential drug-drug interactions between PIs and
      some statins, which are drugs frequently used to treat hyperlipidemia. We
      performed a retrospective cohort study using the TennCare program to determine
      prescribing rates of contraindicated combinations of PIs and statins in HIV
      infected persons in Tennessee and to assess changes in prescribing after
      publication of treatment guidelines. Computerized files identified adult patients
      with antiretroviral prescriptions and overlapping prescriptions for PIs and
      statins from January 1, 1996 through June 30, 2002. A subset of these
      combinations was defined as contraindicated based on published guidelines.
      Changes in patterns of prescribing after publication of preliminary treatment
      guidelines were examined using a mixed-effects logistic regression model. There
      were 3448 persons who received PIs during the study period. The proportion of PI
      users receiving statins increased from 3.5% during January 1996 through December
      2000 to 7.9% during January 2001 through June 2002 (P < 0.001). Contraindicated
      PI-statin use decreased from 42.0% of combinations to 20.8% during the same
      periods (P < 0.001). Use of PIs and statins has increased in the adult TennCare
      population. Contraindicated combinations have decreased but remain unacceptably
      high.

PMID- 15735446
TI  - Why are baseline HIV RNA levels 100,000 copies/mL or greater associated with
      mortality after the initiation of antiretroviral therapy?
AB  - BACKGROUND: There is conflicting evidence regarding the impact of baseline plasma
      HIV RNA on virologic responses after the initiation of triple-drug antiretroviral
      therapy (highly active antiretroviral therapy [HAART]). This has made it
      difficult to interpret the recently reported association between baseline plasma
      HIV RNA and mortality. We evaluated whether baseline CD4 cell count and plasma
      HIV RNA predicted virologic suppression (<500 copies/mL) and rebound (> or =500
      copies/mL) among adherent HIV-infected patients. METHODS: Antiretroviral-naive
      HIV-infected patients were stratified by baseline CD4 cell count, plasma HIV RNA,
      and adherence level. Cox and logistic regression were used to evaluate the time
      to suppression and rebound and the odds of ever achieving HIV RNA suppression.
      RESULTS: A total of 1422 individuals initiated HAART between August 1, 1996 and
      July 31, 2000 and were followed to March 31, 2002. Adherent patients with HIV RNA
      levels > or =100,000 copies/mL and 50 to 99,999 copies/mL were slower to suppress
      HIV RNA than patients with baseline HIV RNA <50,000 copies/mL in Kaplan-Meier
      analyses. Although the odds of RNA suppression among adherent patients with
      baseline RNA levels <50,000 copies/mL and 50 to 99,999 copies/mL were similar (P
      = 0.197), patients with baseline HIV RNA > or =100,000 copies/mL were markedly
      less likely ever to achieve suppression during follow-up (adjusted odds ratio:
      0.27 [95% confidence interval: 0.13-0.54]; P < 0.001). No differences in the rate
      of virologic rebound were observed between adherent patients in the various
      baseline HIV RNA strata, and CD4 cell count was not associated with suppression
      or rebound. CONCLUSIONS: Baseline HIV RNA > or =100,000 copies/mL was associated
      with a significantly lower likelihood of ever achieving HIV RNA suppression
      during follow-up. These findings likely explain the association between baseline
      HIV RNA levels and mortality and have important implications for the development
      of therapeutic guidelines.

PMID- 15735445
TI  - Persistence of nevirapine exposure during the postpartum period after intrapartum
      single-dose nevirapine in addition to zidovudine prophylaxis for the prevention
      of mother-to-child transmission of HIV-1.
AB  - OBJECTIVE: To determine nevirapine (NVP) plasma levels during the postpartum
      period after a single intrapartum NVP dose for the prevention of mother-to-child
      transmission. METHODS: Plasma samples at delivery and during days 8 to 45
      postpartum were obtained from HIV-infected Thai women who received an intrapartum
      NVP dose in the Perinatal HIV Prevention Clinical Trial-2 (PHPT-2) for the
      prevention of perinatal HIV transmission. These data were combined with NVP
      concentration data from 2 phase 1 studies of NVP for a population analysis.
      RESULTS: The median NVP level fell to 68 ng/mL (range: <50-228, n = 43) 8 to 14
      days after dosing and to 51 ng/mL (range: <50-166, n = 25) between 15 and 21
      days. During the second and third weeks postpartum, NVP levels were below the
      limit of quantitation in 23% and 44% of samples, respectively. Between 21 and 45
      days, no sample had a quantifiable NVP concentration. A simulation derived from
      the population analysis predicts that NVP concentration falls to less than 10
      ng/mL in 5% of women by 11 days, in 50% of women by 17.5 days, and in 95% of
      women by 28 days. CONCLUSIONS: Significant NVP concentrations remained for up to
      20 days in these Thai women. To ensure that coverage is maintained until NVP
      concentrations fall to nonsuppressive levels, 1 month of additional
      antiretroviral treatment after delivery should be considered to prevent the
      emergence of resistant viruses.

PMID- 15735447
TI  - Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable
      for nevirapine, efavirenz, or both drugs combined and is not predictive of long
      term virologic efficacy: A 2NN substudy.
AB  - BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed
      as a marker of early efficacy of antiretroviral therapy (ART) and a possible
      predictor of late efficacy. We compared the rate of pVL decline in patients
      starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in
      addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral
      decay constant (VDc) during the first 2 weeks of treatment in patients enrolled
      in the 2NN study who remained on allocated treatment. RESULTS: The median VDc
      (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25
      0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a
      baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3)
      times more likely to have a VDc >75th percentile. A high VDc was not associated
      with plasma drug concentration or with a decreased risk of virologic failure at
      week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2).
      CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar
      rates of pVL decline during the first 2 weeks of treatment. The VDc with these
      regimens is not predictive of late virologic efficacy.

PMID- 15735448
TI  - Serum hypophosphatemia in tenofovir disoproxil fumarate recipients is
      multifactorial in origin, questioning the utility of its monitoring in clinical
      practice.
AB  - Tenofovir disoproxil fumarate (TDF) has been anecdotally associated with isolated
      hypophosphatemia (HP) as well as proximal tubular toxicity and renal dysfunction
      in which HP has consistently been a feature. Consequently, routine phosphate
      measurements in TDF recipients have been recommended. We identified and compared
      the frequency of HP in TDF recipients with that in non-TDF recipients; assessed
      the reproducibility of HP; identified the incidence of renal dysfunction in
      hypophosphatemic patients; and evaluated associations between HP and host, HIV
      infection, or treatment factors. This prospective observational study measured
      serum phosphate, urea, and creatinine in HIV-positive individuals among the
      following treatment groups: TDF-containing highly active antiretroviral therapy
      (HAART, group A), TDF-sparing HAART (group B), HAART naive (group C), and off
      HAART but treatment experienced (group D). Phosphate measurements were obtained
      in 252 patients. Seventy-two percent of patients prescribed TDF received a
      phosphate measurement. The frequency of HP in groups A, B, C, and D was 31%, 22%,
      10%, and 14%, respectively. Seventy-eight percent of phosphate measurements were
      reproducible. Kaletra (P = 0.016) administration and duration of antiretroviral
      therapy (P = 0.023) were independently associated with HP, but elevated
      creatinine and urea or use of TDF was not. The etiology of HP seems to be
      multifactorial and unrelated to TDF or renal dysfunction. This questions the
      utility of routine phosphate testing, in isolation, in TDF recipients.

PMID- 15735449
TI  - T-Cell surface CCR5 density is not correlated with hepatitis severity in
      hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic
      use of CCR5 antagonists.
AB  - CCR5 antagonists represent promising anti-HIV agents. Yet, if the CCR5 chemokine
      receptor plays a positive role in hepatitis C virus (HCV) infection, CCR5
      antagonists might be contraindicated in HCV/HIV-coinfected subjects. Therefore,
      we tested the hypothesis that the level of T-cell surface CCR5 expression, which
      might determine the intensity of HCV-specific T-cell recruitment into the liver,
      and thereby the efficiency of the anti-HCV response, could determine HCV disease
      evolution. For this purpose, we compared CCR5 density, measured by quantitative
      flow cytometry at the surface of nonactivated (human leukocyte antigen-D-related
      [HLA-DR]-) T cells of 51 HCV/HIV patients, with HCV load, serum aminotransferase
      levels, and liver histology (inflammatory activity, fibrosis, and rate of
      fibrosis progression). DR-CD4+ T-cell surface CCR5 density, which correlated with
      DR-CD8+ T-cell surface CCR5 density and was stable over time in HCV/HIV
      coinfected individuals, did not correlate with any of the biologic parameters of
      HCV infection analyzed and was not linked to the capacity to clear the virus. In
      conclusion, we failed to demonstrate any impact of interindividual variability in
      T-cell surface CCR5 density on HCV infection, which would have argued against the
      use of CCR5 antagonists in HIV/HCV-coinfected subjects.

PMID- 15735450
TI  - Increased CD36 expression on circulating monocytes during HIV infection.
AB  - BACKGROUND: Metabolic alterations and abnormalities of fat distribution are
      common findings in antiretroviral-treated HIV-1-infected patients. CD36 is a
      multifunctional receptor with a wide tissue distribution that plays a crucial
      role in the cellular uptake and metabolism of lipids. OBJECTIVES: To define the
      level of CD36 expression on circulating monocytes from HIV-1-infected patients
      and healthy controls (HCs) and to correlate CD36 expression levels with metabolic
      and immunovirologic parameters. METHODS: CD36 expression on peripheral blood
      monocytes was measured by means of flow cytometry in 165 HIV-1-infected patients
      and in 35 HCs. Statistical analysis was performed by means of univariate and
      multivariate analysis of variance models. RESULTS: CD36 expression was
      significantly higher in HIV-1-infected patients compared with HCs (P < 0.0001).
      HIV-1 infection was the only variable associated with CD36 expression on
      multivariate analysis, whereas no correlation was found between CD36 level and
      age, sex, body mass index, lipid serum levels, HIV RNA levels, time on
      antiretroviral therapy, or kind of antiretroviral regimen. CONCLUSIONS: HIV-1
      infection is associated with increased expression of CD36 on circulating
      monocytes, and antiretroviral drugs play only a minor role in the complex
      homeostasis of this receptor. Given its role in the cellular uptake and
      accumulation of lipids, CD36 increased levels on monocytes could represent a
      proatherogenic condition in HIV-infected patients.

PMID- 15735451
TI  - HIV infection and sexually transmitted diseases in female commercial sex workers
      in China.
AB  - A cross-sectional survey was conducted among female commercial sex workers (FSWs)
      in Zhengzhou, China, to estimate rates of HIV infection and sexually transmitted
      diseases (STDs) and to document their sexual behavior patterns from October 2000
      to January 2001. FSWs were recruited by the snowball sampling technique and were
      interviewed at their working environments anonymously. This strategy resulted in
      high rates of response (92%) and concordance (98%) to sensitive questions. A
      total of 621 FSWs were enrolled. One direct FSW and 1 indirect FSW were positive
      for antibodies to HIV in oral fluids (prevalence of HIV infection, 1.4% and 0.2%,
      respectively). A history of STDs was reported by 49% of the FSWs. Most FSWs (87%)
      reported inconsistent condom use. Ten percent of FSWs recognized their clients as
      drug users. A few FSWs (2.2%) were injecting drug users, of whom 2 reported
      incidents of sharing needles/syringes with other injecting drug users. Direct
      FSWs had more risk characteristics and were more vulnerable to HIV infection and
      STDs than indirect FSWs. Inconsistent use of condoms and a high level of STDs
      underscore the urgent need to implement intervention strategies and condom
      promotion, particularly among direct sex workers in China.

PMID- 15735452
TI  - Interruption and discontinuation of highly active antiretroviral therapy in the
      multicenter AIDS cohort study.
AB  - OBJECTIVE: Identify the determinants and consequences of interrupting and
      discontinuing highly active antiretroviral therapy (HAART) among a population
      based cohort of HIV-infected men. METHODS: Longitudinal analyses were applied to
      2916 person-visit pairs (589 men) of continuous HAART use, 243 person-visit pairs
      (154 men) during which HAART was interrupted, and 151 person-visit pairs (130
      men) in which HAART was discontinued by the second visit. HIV RNA increase was
      defined as > or =1 log10 copies/mL across the visit pairs. RESULT: : Younger age,
      black race, geographic location, higher HIV RNA level, depression, shorter time
      on HAART, lower medication adherence, and not taking a lamivudine-containing
      regimen predicted interrupting HAART use. Younger age, higher HIV RNA level,
      depression, and taking an abacavir- or lopinavir-containing regimen predicted
      discontinuing HAART. Among men with < or =1000 HIV RNA copies/mL, approximately
      5% of those who interrupted HAART for < or =7 days and those who continued HAART
      had an HIV RNA increase. Men with longer interruptions and HAART discontinuers
      had significantly higher rates of HIV RNA increases (35.7% and 70.5%,
      respectively). Discontinuation and long interruptions resulted in lower CD4 cell
      counts. CONCLUSIONS: Host characteristics play a role in short interruptions,
      whereas longer interruptions may be clinically indicated. These longer stoppages
      had further virologic and immunologic consequences, however.

PMID- 15735453
TI  - Associations of sexual risk taking among Kenyan female sex workers after
      enrollment in an HIV-1 prevention trial.
AB  - BACKGROUND: Female sex workers (FSWs) often lack the ability to negotiate safer
      sex and are at high risk for HIV-1 infection and sexually transmitted infections
      (STIs). METHODS: Seronegative FSWs were enrolled in an STI/HIV-1 prevention trial
      in Nairobi, Kenya. Demographics and sexual risk taking were assessed every 3
      months. Predictors of reduced risk taking were defined using multivariate
      logistic regression. RESULTS: Four hundred sixty-six FSWs were enrolled and
      followed for just over 2 years each. A spectrum of sex work was apparent: FSWs
      working in night clubs were younger, charged more for sex, and used condoms more
      frequently; FSWs working from home were older, charged less, and used condoms the
      least; and those working in bars were intermediate. Increases in reported condom
      use were most significant and sustained for FSWs working from home and charging
      less for sex and were poorly maintained for bar-based FSWs. Self-reported lower
      condom use, higher client numbers, and alcohol use were associated with higher
      STI rates. CONCLUSIONS: Home-based FSWs and those charging less for sex used
      condoms the least at baseline but showed the greatest and most sustained
      improvements over time. Potential response heterogeneity in FSW subgroups should
      be considered in the design of HIV-1 prevention programs.

PMID- 15735454
TI  - Baseline plasma viral load and CD4 cell percentage predict survival in HIV-1- and
      HIV-2-infected women in a community-based cohort in The Gambia.
AB  - OBJECTIVES: To estimate and compare the all-cause mortality rates among HIV-1
      infected, HIV-2-infected, and uninfected women and to assess the predictive value
      of baseline plasma viral load (PVL) and CD4 cell percentage (CD4%) for mortality.
      DESIGN: Cohort study. METHODS: At presentation to antenatal clinics in The Gambia
      in 1993-1995, pregnant women were screened for antibodies to HIV-1 and HIV-2.
      Seropositive subjects and a similar number of seronegative controls were
      enrolled, and baseline PVL and CD4% were measured. Participants were visited
      regularly by field-workers until 18 months after delivery and again 4-7 years
      later. RESULTS: Thirty-two of 101 women infected with HIV-1, 23 of 243 infected
      with HIV-2, and 9 of 468 seronegative women died during a median follow-up of 6.9
      years. The mortality rate was 56 deaths per 1000 person years of observation
      (pyo) for HIV-1-infected, 16 deaths per 1000 pyo for HIV-2-infected, and 3.1
      deaths per 1000 pyo for HIV-uninfected women. After 8 years of follow-up, >50% of
      HIV-1-infected women were still alive. In multivariate analysis, a 1-log increase
      of HIV-1 PVL was associated with a 1.8-fold higher rate of mortality (95%
      confidence interval [CI], 0.9-3.4). In HIV-2 infection, women with a high PVL
      (>10,000 copies/mL) had an 8.7-fold (95% CI, 2.8-28) higher rate of mortality
      than did those with a low PVL (<1000 copies/mL). A 10% decrease in CD4% was
      associated with higher mortality rates among HIV-1-infected (1.6-fold; 95% CI,
      1.1-2.3) and HIV-2-infected (1.5-fold; 95% CI, 1.0-2.3) subjects. DISCUSSION:
      Survival of HIV-1-infected women in The Gambia is similar to that in
      industrialized countries before the introduction of antiretroviral treatment.
      Survival of HIV-2-infected women is much better. However, women with high PVLs
      die as quickly as their HIV-1-infected counterparts.

PMID- 15735455
TI  - Managed care for AIDS patients: is bigger better?
AB  - CONTEXT: Medicaid provides funds for the majority of AIDS-related health care
      services in the United States. In an effort to stabilize steeply rising Medicaid
      costs, managed care programs are replacing traditional fee-for-service Medicaid
      services. OBJECTIVE: To assess the impact of patient volume on the quality of
      care received by AIDS patients within a state's Medicaid managed care system.
      DESIGN: Cohort study of AIDS patients who were enrolled in Medicaid at any time
      from July 1997 through December 1998. Patient charts were reviewed and
      abstracted. Additional information on the AIDS patients' mode of exposure, date
      of AIDS diagnosis, and vital status were obtained from the state's HIV/AIDS
      surveillance database. PATIENTS AND SETTING: All known AIDS patients enrolled in
      the Maryland Medicaid managed care program were eligible. A total of 1052 of 1585
      patient records were reviewed and analyzed. MAIN OUTCOME MEASURES: CD4 and viral
      load tests; preventive health care including screening for sexually transmitted
      infections; placement of tuberculin purified protein derivative (PPDs); hepatitis
      B and C screening; vaccination for hepatitis B; vaccination for pneumococcal
      pneumonia; Papanicolaou test screening; medication utilization including receipt
      of antiretroviral therapy and prophylaxis against Pneumocystis carinii pneumonia;
      case management services; and mortality. RESULTS: Health care quality indicators
      were examined by comparing the performance of clinical sites that saw a low
      volume of Medicaid AIDS patients per site (1-15 patients), a medium volume (16
      100 patients), and a high volume (101-500 patients). High-volume sites performed
      better on virtually all quality indicators. There were few differences in
      performance between low- and medium-volume sites. High-volume sites experienced a
      greater number of patient deaths; this was true after adjusting for potential
      confounders such as age, use of antiretrovirals, time since AIDS diagnosis,
      appropriate laboratory monitoring, and hospitalizations. CONCLUSIONS: Variations
      in quality of care for AIDS patients were observed in a statewide managed care
      system. These variations existed despite provisions to ensure quality care such
      as an enhanced payment system for managed care organizations providing services
      for AIDS. High-volume sites were more likely to adhere to Public Health Service
      guidelines and may offer the best opportunity to provide high-quality AIDS care.

PMID- 15735456
TI  - Choosing HIV Counseling and Testing Strategies for Outreach Settings: A
      Randomized Trial.
AB  - BACKGROUND: In surveys, clients have expressed preferences for alternatives to
      traditional HIV counseling and testing. Few data exist to document how offering
      such alternatives affects acceptance of HIV testing and receipt of test results.
      OBJECTIVES: This randomized controlled trial compared types of HIV tests and
      counseling at a needle exchange and 2 bathhouses to determine which types most
      effectively ensured that clients received test results. METHODS: Four
      alternatives were offered on randomly determined days: (1) traditional test with
      standard counseling, (2) rapid test with standard counseling, (3) oral fluid test
      with standard counseling, and (4) traditional test with choice of written pretest
      materials or standard counseling. RESULTS: Of 17,010 clients offered testing,
      7014 (41%) were eligible; of those eligible, 761 (11%) were tested: 324 at the
      needle exchange and 437 at the bathhouses. At the needle exchange, more clients
      accepted testing (odds ratio [OR] = 2.3; P < 0.001) and received results (OR =
      2.6; P < 0.001) on days when the oral fluid test was offered compared with the
      traditional test. At the bathhouses, more clients accepted oral fluid testing (OR
      = 1.6; P < 0.001), but more clients overall received results on days when the
      rapid test was offered (OR = 1.9; P = 0.01). CONCLUSIONS: Oral fluid testing and
      rapid blood testing at both outreach venues resulted in significantly more people
      receiving test results compared with traditional HIV testing. Making counseling
      optional increased testing at the needle exchange but not at the bathhouses.

PMID- 15735458
TI  - Comparable pharmacokinetics of generic indinavir (Inhibisam) versus brand
      indinavir (Crixivan) when boosted with ritonavir.

PMID- 15735457
TI  - Molecular epidemiology of HIV-1 subtypes in southern China.
AB  - The driving forces of the HIV-1 epidemic in Guangxi, China were assessed by
      investigating virologic and epidemiologic data from a cohort of longitudinally
      followed injection drug users (IDUs) in Binyang and Pingxiang, major urban areas
      along 2 separate drug routes in the province. Sera and interview data were
      obtained in September and October of 2000. Sequence analysis of HIV-1 was
      performed on the gag-pol region (HXB2 nt 1850-3005) and C2 to V4 env (HXB2 nt
      6704-7626). Sequence data demonstrated that 88% of the infections in Pingxiang
      were CRF01_AE, whereas 96% in Bin-yang were CRF08_BC. Three recently infected
      subjects in Pingxiang were infected with CRF08_BC, and 1 chronically infected
      subject had evidence of a recombinant virus. Intersubject distances were
      statistically greater for CRF01_AE-infected subjects than CRF08_BC-infected
      subjects for all regions except V4. The epidemic in Binyang is similar to
      previously described IDU-based epidemics, with a strong founder effect with
      little variation in V3. The epidemic in Pingxiang may have had multiple
      introductions of the CRF01_AE epidemic into the city and greater spread through
      sexual transmission, resulting in greater variation in V3 than typically seen in
      purely parenterally based epidemics.

PMID- 15735459
TI  - Prevalence and persistence of nonnucleoside reverse transcriptase inhibitor
      mutations in the female genital tract.

PMID- 15735460
TI  - Adhesive dentistry and endodontics: materials, clinical strategies and procedures
      for restoration of access cavities: a review.
AB  - The complexity of restorative dentistry has increased greatly in recent years,
      with the myriad of products used in "adhesive dentistry." So too has the "simple"
      matter of restoring access cavities after completion of endodontic treatment.
      This review discusses current methods of "bonding" to tooth structure, ceramic
      materials, and metals, with emphasis on those aspects that are important to
      endodontics. Specific materials, procedures and major decision making elements
      are discussed, as well as how to avoid problems in compatibility between
      endodontic and restorative materials.

PMID- 15735461
TI  - In vivo debridement efficacy of ultrasonic irrigation following hand-rotary
      instrumentation in human mandibular molars.
AB  - This study histologically compared the in vivo debridement efficacy of
      hand/rotary canal preparation versus a hand/rotary/ultrasound technique in mesial
      root canals of vital mandibular molars. Group 1 consisted of 16 teeth prepared
      with a hand/rotary technique whereas group 2 consisted of 15 teeth prepared in
      similar fashion but followed by 1 min of ultrasonic irrigation, per canal,
      utilizing an ultrasonic needle in a MiniEndo unit. Five uninstrumented mandibular
      molars served as histologic controls. After extraction and histologic
      preparation, 0.5 microm cross-sections, taken every 0.2 mm from the 1- to 3-mm
      apical levels, were evaluated for percentage of tissue removal. Nonparametric
      analysis revealed mean percent canal and isthmus cleanliness values to be
      significantly higher for group 2 at all levels evaluated, except one. In
      conclusion, the 1 min use of the ultrasonic needle after hand/rotary
      instrumentation resulted in significantly cleaner canals and isthmuses in the
      mesial roots of mandibular molars.

PMID- 15735462
TI  - Effect of MTAD on postoperative discomfort: a randomized clinical trial.
AB  - The purpose of this study was to compare levels of postoperative discomfort after
      cleaning and shaping of root canals using two protocols for removal of smear
      layer. Seventy-three consecutive patients requiring root canal treatment were
      included. At random, canals were cleaned and shaped with one of the following
      protocols. In group 1, 5.25% sodium hypochlorite was used as the root canal
      irrigant. The smear layer was removed by placing 17% EDTA in the canal(s) for 1
      min followed by a 5-ml rinse with 5.25% NaOCl. In group 2, canals were irrigated
      with 1.3% NaOCl; the smear layer was removed by placing MTAD in the canal(s) for
      5 min. Access cavities were closed with a sterile cotton pellet and Cavit. The
      patients recorded degree of discomfort at various time intervals after cleaning
      and shaping on a visual analogue scale for 1 wk. No significant statistical
      difference was found in the degree of discomfort between the two groups (p =
      0.58).

PMID- 15735463
TI  - The effect of the distance between post and residual gutta-percha on the clinical
      outcome of endodontic treatment.
AB  - To determine whether the distance between the post and the residual gutta-percha
      influences the clinical outcome of endodontic treatment, 94 endodontically
      treated teeth following post and core restoration were evaluated
      radiographically. The teeth were divided into three groups: (I) no gap between
      the gutta-percha and the post; (II) a gap of >0 to 2 mm; (III) a gap of >2 mm.
      Treatment outcome was evaluated in follow-up radiographs, taken 1 yr after
      treatment and up to 5 yr posttreatment. In group I, 83.3% of the teeth were
      evaluated normal, 53.6% of group II, and only 29.4% of group III. A gap between
      the gutta-percha and the post was related to an increased rate of emerged disease
      in endodontically treated teeth restored with a post and core.

PMID- 15735464
TI  - An in vitro comparison of the rake angles between K3 and ProFile endodontic file
      systems.
AB  - The purpose of this study was to compare rake angles of the ProFile and K3 file
      systems. Twenty-five 40/0.06 taper files were obtained for each system. Five
      files from the same manufacturer were placed perpendicularly into a vial of
      Epoxicure Resin and left to set for 24 h. The set-ups were removed from the vials
      and each were sectioned 5 mm from the tip of the files and polished. A
      photomicrograph was taken of each file with 100x magnification. Five sets of
      ProFile and five sets of K3 files were processed in this manner. Images were
      captured digitally, and rake angles of each file were measured. Multivariate
      ANOVA found a significant difference (p < 0.001) among the three negative rake
      angles of the ProFile system compared with the K3 system.

PMID- 15735465
TI  - Effect of cyclic fatigue on static fracture loads in ProTaper nickel-titanium
      rotary instruments.
AB  - The aim of the present study was to evaluate static fracture loads of ProTaper
      Nickel-Titanium instruments that had been subjected to various degrees of cyclic
      fatigue. Torque and angle at failure of new instruments and instruments that had
      been stressed to 30, 60, or 90% of their cyclic fatigue rotations in a simulated
      canal (90 degrees and 5 mm radius) were tested according to ISO 3630-1. With
      unused ProTaper instruments, resistance to cyclic fatigue decreased with diameter
      increase and ranged from 158 to 450 rotations. Torque at failure ranged from 0.5
      to 2.1 Ncm and showed a strong linear relationship to instrument diameter (r =
      0.9) while angle at failure was weakly related to diameter (r = 0.46). Cyclic
      prestressing significantly reduced torsional resistance in finishing files, while
      shaping files were largely unaffected. In conclusion, build-up of tension within
      NiTi rotary instruments depends on instrument diameter. Clinically, larger
      instruments that have been subjected to some cyclic fatigue should be used with
      great care or discarded.

PMID- 15735466
TI  - Effects of endodontic irrigation solutions on mineral content of root canal
      dentin using ICP-AES technique.
AB  - The aim of this in vitro study was to evaluate mineral content of root canal
      dentin after treatment with several endodontic irrigation solutions. Sixty
      mandibular anterior teeth extracted for periodontal reasons used. The crowns of
      the teeth were removed at the cemento-enamel junction. Pulp tissues were removed
      and the teeth were randomly divided into six groups including 10 teeth each. Root
      canals were enlarged with gates-glidden burs (# 1, 2, and 3). The groups were
      treated as follows: group 1, 0.2% chlorhexidine gluconate for 15 min; group 2, 3%
      H2O2 for 15 min; group 3, 17% EDTA for 15 min; group 4, 5.25% NaOCl for 15 min;
      group 5, 2.5% NaOCl for 15 min; and group 6, distilled water (control). Dentin
      chips were obtained using gates-glidden burs (# 4, 5, and 6). The levels of five
      elements calcium, phosphorus, magnesium, potassium, and sulfur in each specimens
      were analyzed using ICP-AES (Inductively Coupled Plasma Atomic Emission
      Spectrometry) technique. Changes in the levels of the chemical elements were
      recorded. The results were then statistically analyzed by one-way ANOVA and Tukey
      tests. There was a significant decrease in the calcium and phosphorus levels
      after treatment with all irrigation solutions except for 5.25% NaOCl when
      compared with the control group (p < 0.05). The K, Mg, and S level changes were
      not statistically significant (p > 0.05). It has been concluded that endodontic
      irrigation solutions have an effect on mineral contents of root dentin.

PMID- 15735467
TI  - An in vitro comparison of the sealing ability of three endodontic sealers used in
      canals with iatrogenic enlargement of the apical constriction.
AB  - In cases of disrupted apical constriction effort is made to create an apical stop
      and subsequently instrument and obturate the canal up to this point. The aim of
      this study was to in vitro evaluate the sealing ability of three root canal
      sealers used with the lateral compaction technique in teeth with enlarged
      constriction. Thirty-six single rooted premolars with straight canals were
      instrumented up to the apical constriction using a step-back technique. The
      constriction was enlarged and root canal instrumentation 1.5 mm short of the
      original working length was performed, to create a new apical stop. Teeth were
      obturated using lateral compaction technique with either Topseal, Roth 811, or
      Apexit. Teeth were subjected to area-metric analysis of dye penetration in
      transverse root sections, up to the most coronal extend of the dye. Sections were
      studied under the stereomicroscope, digital images were processed and leakage
      area was estimated. Statistical analysis was performed using Student's t test and
      Wilcoxon matched-pairs signed-rank test. No gutta-percha was extruded into the
      space between the apical constriction and the new iatrogenically created
      constriction. Topseal showed statistical significant less leakage. No significant
      difference was found between Apexit and Roth 811 (t = 0.99; p = 0.75).

PMID- 15735468
TI  - Vasorelaxant effect of resin-based, single-bottle dentin bonding systems.
AB  - Single-bottle dentin bonding systems are currently in wide use. Because these
      materials are sometimes inadvertently placed on microscopic pulp exposures while
      at other times deliberately on frank exposures, their effects on pulpal soft
      tissues need to be evaluated. The present study assessed the vascular effects of
      3M Single Bond (3MSB) and Prime & Bond NT (PBNT), using rat aortic ring
      preparations. It is hypothesized that these bonding agents induce relaxation of
      these preparations. Both 3MSB and PBNT caused endothelium-dependent and 
      independent relaxations in a concentration-dependent manner. The endothelium
      dependent relaxation was associated with the release of nitric oxide. However,
      the responses to both agents did not involve the generation of prostanoids or
      KATP channel activation. At relatively low concentrations, the responses of
      endothelium-denuded tissues to 3MSB were greater than those to PBNT, indicating
      certain differences in the vascular action between these products. The data
      suggest that 3MSB and PBNT interfere with vascular function by causing
      vasorelaxation via mechanisms occurring in the smooth muscle and endothelium,
      including the release of nitric oxide. Among others, this effect may promote
      bleeding if these adhesives are placed on pulp exposures.

PMID- 15735469
TI  - Comparison of generated forces and apical microleakage using nickel-titanium and
      stainless steel finger spreaders in curved canals.
AB  - The purpose of this study was to compare (a) forces generated during lateral
      compaction and (b) apical microleakage for nickel-titanium (NiTi) and stainless
      steel (SS) finger spreaders. Twenty-eight extracted human teeth were instrumented
      using a standardized rotary instrumentation technique. NiTi and SS #30 spreaders
      were used to obturate molar roots while the forces generated during obturation
      were measured on a Universal testing machine. Apical microleakage was determined
      using a fluid filtration method. There was no significant difference in
      microleakage between spreaders. NiTi spreaders produced significantly less force
      than SS spreaders in all specimens (p < 0.001).

PMID- 15735470
TI  - Pulp tissue reactions to a dentin bonding agent as a direct capping agent.
AB  - The aim of this study was to investigate the response of human pulp tissue to a
      dentin bonding agent, Scotchbond Multi-Purpose Plus (SMPP), in exposed class V
      cavities. Sixteen human premolar teeth were mechanically exposed. Ten pulps were
      capped with SMPP and six teeth were capped with Dycal. The cavities were filled
      with a composite. After 40 days, the teeth were extracted and processed for
      histologic evaluation. Of the 10 teeth capped with SMPP, eight showed moderate
      chronic inflammation, one was severely inflamed, and one pulp had no to slight
      inflammation. None of the teeth capped with SMPP showed dentin bridge formation.
      Of the six teeth capped with Dycal, three exhibited incomplete dentin bridges
      associated with no to slight inflammation, and three showed no to slight
      inflammation, without formation of dentin bridges. Direct capping with Dycal with
      subsequent sealing with SMPP may show favorable results in pulp tissue. SMPP may
      cause inflammatory changes when applied directly to exposed pulp tissue.

PMID- 15735472
TI  - Evaluation of the flexural strength of carbon fiber-, quartz fiber-, and glass
      fiber-based posts.
AB  - This study investigated the flexural strength of eight fiber posts (one carbon
      fiber, one carbon/quartz fiber, one opaque quartz fiber, two translucent quartz
      fiber, and three glass fiber posts). Eighty fiber posts were used and divided
      into eight groups (n = 10): G1: C-POST (Bisco); G2: AESTHETI-POST (Bisco); G3:
      AESTHETI-PLUS (Bisco); G4: LIGHT-POST (Bisco); G5: D.T. LIGHT-POST (Bisco); G6:
      PARAPOST WHITE (Coltene); G7: FIBERKOR (Pentron); G8: REFORPOST (Angelus). All of
      the samples were tested using the three-point bending test. The averages obtained
      were submitted to the ANOVA and to Tukey's test (p < 0.05). The mean values (MPa)
      of the groups AESTHETI-POST-carbon/quartz fiber post (Bisco) and AESTHETI-PLUS
      quartz fiber post (Bisco) were statistically similar and higher than the mean
      values of the other groups. The mean values of the groups C-POST-carbon fiber
      post (Bisco), LIGHT-POST-translucent quartz fiber post (Bisco), D.T. LIGHT-POST
      double tapered translucent quartz fiber post (Bisco), PARAPOST WHITE-glass fiber
      post (Coltene) and FIBREKOR--glass fiber post (Pentron) were similar and higher
      than the group REFORPOST-glass fiber post (Angelus).

PMID- 15735471
TI  - Preferential attachment of human gingival fibroblasts to the resin ionomer
      Geristore.
AB  - The resin ionomer Geristore has been used extensively for root perforation
      repairs. The purpose of this study was to evaluate oral in vitro biocompatibility
      of the resin ionomer Geristore compared to two other dental perforation repair
      materials, Ketac-Fil and Immediate Restorative Material (IRM). Growth and
      morphology of human gingival fibroblasts (HGFs) was determined using scanning
      electron microscopy (SEM) of HGFs cells grown on test materials as well as
      cytotoxicity assays using eluates from test materials. SEM analysis showed that
      HGFs attached and spread well over Geristore with relatively normal morphology.
      SEM showed that fibroblasts did not attach and spread well over Ketac-Fil or IRM
      as cells appeared much fewer with rounded and different morphology than
      fibroblasts grown on Geristore. Cytotoxicity assays indicated that HGFs
      proliferated in the presence of Geristore eluates and not in the presence of
      Ketac-Fil or IRM eluates. In vitro interpretation indicates that Geristore is
      less cytotoxic to gingival fibroblasts.

PMID- 15735473
TI  - MTA repair of a supracrestal perforation: a case report.
AB  - Root perforations are undesired complications of endodontic treatment. In the
      recent literature, MTA has been regarded as an ideal material for perforation
      repair. This article describes a case report where an iatrogenic supracrestal
      perforation was repaired successfully with mineral trioxide aggregate (MTA).

PMID- 15735475
TI  - Chronic abdominal pain in children: a clinical report of the American Academy of
      Pediatrics and the North American Society for Pediatric Gastroenterology,
      Hepatology and Nutrition.
AB  - Children and adolescents with chronic abdominal pain pose unique challenges to
      their caregivers. Affected children and their families experience distress and
      anxiety that can interfere with their ability to perform regular daily
      activities. Although chronic abdominal pain in children is usually attributable
      to a functional disorder rather than to organic disease, numerous misconceptions,
      insufficient knowledge among health care professionals and inadequate application
      of knowledge may contribute to a lack of effective management. This clinical
      report accompanies a technical report on childhood chronic abdominal pain and
      provides guidance for the clinician in the evaluation and treatment of children
      with chronic abdominal pain. The conclusions are based on the evidence reviewed
      in the technical report and on consensus achieved among subcommittee members.

PMID- 15735476
TI  - Chronic Abdominal Pain In Children: a Technical Report of the American Academy of
      Pediatrics and the North American Society for Pediatric Gastroenterology,
      Hepatology and Nutrition.
AB  - Chronic abdominal pain, defined as long-lasting intermittent or constant
      abdominal pain, is a common pediatric problem encountered by primary care
      physicians, medical subspecialists and surgical specialists. Chronic abdominal
      pain in children is usually functional-that is, without objective evidence of an
      underlying organic disorder. The Subcommittee on Chronic Abdominal Pain of the
      American Academy of Pediatrics and the North American Society for Pediatric
      Gastroenterology, Hepatology and Nutrition has prepared this report based on a
      comprehensive, systematic review and rating of the medical literature. This
      report accompanies a clinical report based on the literature review and expert
      opinion. The subcommittee examined the diagnostic and therapeutic value of a
      medical and psychologic history, diagnostic tests, and pharmacological and
      behavioral therapy. The presence of alarm symptoms or signs (such as weight loss,
      gastrointestinal bleeding, persistent fever, chronic severe diarrhea and
      significant vomiting) is associated with a higher prevalence of organic disease.
      There was insufficient evidence to state that the nature of the abdominal pain or
      the presence of associated symptoms (such as anorexia, nausea, headache and joint
      pain) can discriminate between functional and organic disorders. Although
      children with chronic abdominal pain and their parents are more often anxious or
      depressed, the presence of anxiety, depression, behavior problems or recent
      negative life events does not distinguish between functional and organic
      abdominal pain. Most children who are brought to the primary care physician's
      office for chronic abdominal pain are unlikely to require diagnostic testing.
      Pediatric studies of therapeutic interventions were examined and found to be
      limited or inconclusive.

PMID- 15735477
TI  - Can we alter the natural history of Crohn disease in children?
AB  - The natural history of Crohn disease is characterized by recurrent bouts of
      active disease, the consequences of which can severely impair sufferers' physical
      and social functioning. Not only does the illness cause day-to-day morbidity for
      children but the consequence of the chronic inflammatory process also commonly
      results in the need for major intestinal surgery. The present challenge facing
      physicians treating children with Crohn disease is to alleviate symptoms and
      prolong periods of remission via the use of specifically targeted therapies while
      minimizing toxicity and promoting normal growth and development. Although
      systemic corticosteroids are effective in inducing clinical remission, they are
      of little or no benefit in maintaining remission and can contribute to linear
      growth retardation. Immunomodulating drugs such as azathioprine, 6-mercaptopurine
      and methotrexate have proved effective for inducing and maintaining remission of
      active Crohn disease. These agents are now commonly prescribed in children at
      diagnosis, after a severe attack or after surgery or in those who become
      corticosteroid-dependent or corticosteroid-resistant. Their use is not without
      potential adverse effects and not all patients respond well to these agents. With
      the introduction of biologic agents, notably the tumor necrosis factor-alpha
      monoclonal antibody infliximab, progress has been made in targeting specific
      pathogenetic mechanisms of Crohn disease and potentially altering the underlying
      disease process. Published experience in children is currently limited, but
      infliximab has been shown to improve symptoms and achieve corticosteroid
      independence in this age group. Unresolved issues with infliximab and other
      emerging biologic agents, including long-term safety, necessitate a degree of
      caution in selecting appropriate patients for treatment and with careful
      monitoring of their effects. The collection of contemporary natural history data
      is crucial to facilitate the better integration of current and emerging therapies
      in an attempt to alter the natural history of Crohn disease in children.

PMID- 15735478
TI  - The Paris Consensus on Childhood Constipation Terminology (PACCT) Group.

PMID- 15735479
TI  - What can we learn from Helicobacter pylori reinfection in childhood?

PMID- 15735480
TI  - Where is celiac disease coming from and why?

PMID- 15735481
TI  - Growth assessment in infants and toddlers using three different reference charts.
AB  - OBJECTIVE: To determine if the proportion of children < or =24 months old in a
      tertiary care facility defined as at risk of undernutrition or overnutrition
      differs according to different references used for assessment: the Centers for
      Disease Control and Prevention (CDC), National Center for Health Statistics
      (NCHS) or Tanner-Whitehouse (Tanner) growth charts for weight-for-age and length
      for-age. METHODS: Lengths and weights were measured on infants (207 female, 341
      male) aged < or =24 months admitted from or attending clinics in the General
      Pediatric or Respiratory Medicine Programs at The Hospital for Sick Children,
      Toronto. Weight-for-age and length-for-age percentiles and percent ideal body
      weight were electronically computed. RESULTS: The proportion of all children
      whose weight-for-age was <3rd percentile (at risk of undernutrition) was greatest
      using the CDC growth charts (22.5%) compared with the NCHS (15.9%) or Tanner
      (19.2%) growth charts. Likewise, the proportion of all infants/toddlers with
      percent ideal body weight <90 (at risk of undernutrition) was greatest using the
      CDC (32.3%) compared with the NCHS (22.1%) or Tanner (25.9%) growth charts. In
      contrast, the percentage of children whose percent ideal body weight was > or
      =110% (at risk of overnutrition) was least using the CDC (18.1%) compared with
      the NCHS (26.1%) or Tanner (22.4%) growth charts. CONCLUSION: More children aged
      < or =24 months will be defined as at risk of undernutrition and fewer at risk of
      overnutrition when using weight-for-age or percent ideal body weight and the CDC
      growth charts compared with the NCHS or Tanner growth charts. As a result,
      requests for a more detailed nutritional assessment for undernutrition will
      likely follow implementation of the CDC growth charts in a tertiary care setting.
      As the CDC, NCHS and Tanner growth charts are growth "references" rather than
      "standards," other than for screening purposes, they should not be used in
      isolation when assessing growth and nutritional status.

PMID- 15735482
TI  - Infected and noninfected ascites in pediatric patients.
AB  - OBJECTIVES: To determine the prevalence of spontaneous bacterial peritonitis,
      ascites with bacterial infection and noninfected ascites in pediatric patients
      with portal hypertensive ascites and to compare the clinical and laboratory
      features of infected and noninfected ascites. METHODS: Forty-one episodes of
      portal hypertensive ascites (serum-ascites albumin gradient >1.1 g/dL) in 31
      patients were studied. Median age was 2.9 years. Twenty-four (77.4%) patients
      were cirrhotic and 20 (83.3%) were classified as Child-Pugh C. Median pediatric
      end-stage liver disease score was 18.5. The following ascites features were
      assessed: polymorphonuclear neutrophil cell count, cytology, pH, concentration of
      glucose, lactic dehydrogenase, total protein and albumin, Gram stain and
      bacteriological culture. Blood was sampled for complete blood count, coagulation
      studies, liver and renal function tests. Groups were compared by Mann-Whitney and
      chi tests (P < 0.05). RESULTS: Noninfected ascites were observed in 29 of 41
      samples, spontaneous bacterial peritonitis in eight of 41 and ascites with
      bacterial infection in four of 41. The most prevalent clinical features were
      fever, voluminous ascites and encephalopathy, but there were no significant
      differences in the clinical features of the groups. All patients with infected
      ascites were cirrhotic. There was no statistical difference in Child-Pugh or
      pediatric end-stage liver disease status between patients with infected and
      noninfected ascites. Culture of ascetic fluid was positive in four of eight cases
      of spontaneous bacterial peritonitis. Gram-negative rods were the most prevalent
      bacteria cultured. Except for serum albumin, no statistical differences in
      biochemical markers were observed between patients with infected and noninfected
      ascites. CONCLUSIONS: The prevalence of infected ascites was 29.2%. With the
      exception of serum albumin, there were no differences in the clinical and
      biochemical features of patients with infected ascites and noninfected ascites.

PMID- 15735483
TI  - Using the concept of Food Based Dietary Guidelines to Develop an Optimized Mixed
      Diet (OMD) for German children and adolescents.
AB  - OBJECTIVE: To apply for the first time FAO/WHO standards for Food Based Dietary
      Guidelines (FBDG) to develop a total diet concept named Optimized Mixed Diet
      (OMD) for children and adolescents in a European country. METHODS: Exact 7-day
      menus were composed for sample age groups of children (4-6 years) and adolescents
      (13-14 years), taking into account the German meal patterns, common non-fortified
      foods, and sensory preferences of children (practical criteria). Food amounts and
      food selection within the menus were optimized so far as to achieve a total of
      reference intakes for 22 nutrients (scientific criteria). Simple food based
      messages were deduced. RESULTS: Compared to the existing high-fat, low plant food
      diet reported from the DONALD Study (Dortmund Nutritional and Anthropometric
      Longitudinally Designed Study), the OMD is lower in fat and saturated fatty acids
      and contains ample amounts of plant foods. Reference nutrient densities for age
      groups between 1 and 18 years were achieved or exceeded, except folate. Foods
      from the optimized menus were summarized into 11 food groups based on nutritional
      and practical considerations. Proportions of food groups by weight are
      independent of age and can be used to recalculate food amounts for various age
      groups or energy requirements, respectively. For simplification, "recommended"
      foods were distinguished from "tolerated" foods by their nutrient densities;
      based on food amounts, 3 simple rules for food consumption were deduced, i.e.
      beverages and plant foods: ample; animal foods: moderate; high-fat, high-sugar
      foods: sparingly. CONCLUSIONS: Exact menus and food amounts are a prerequisite to
      ascertain nutrient adequacy of FBDG. The OMD demonstrates that a single diet
      concept with a core of quantified food groups can be adequate for age groups
      between 1 and 18 years within a country, such as Germany.

PMID- 15735484
TI  - Celiac disease in children with diarrhea is more frequent than previously
      suspected.
AB  - BACKGROUND: Celiac disease (CD) may be missed or diagnosed late in children with
      chronic diarrhea. In this study the authors estimated the frequency of CD among
      pediatric patients with chronic diarrhea based on serologic and pathologic
      examinations. METHODS: During a 6-year period, all patients with chronic diarrhea
      of more than 6 weeks referred to the authors' department were included. For each
      patient, an asymptomatic control was enrolled from among the patients referred to
      our clinic for other reasons. Serologic tests for CD including immunoglobulin A
      endomysial antibody and immunoglobulin A antigliadin antibody were performed in
      all patients and controls. If positive, duodenal biopsy was performed to confirm
      the diagnosis. Patients subsequently diagnosed as CD were placed on a gluten-free
      diet and reevaluated after 6 months. RESULTS: 825 cases of diarrhea and 825
      controls were enrolled. CD was diagnosed in 54 (6.5%) of the diarrhea patients
      and seven (0.8%) of the controls. After 6 months of gluten-free diet, 48 (88.8%)
      patients had significant improvement in symptoms and of these 41 (76.1%) were
      totally asymptomatic. Forty-two patients allowed repeat endoscopy after 6 months
      of gluten-free diet and 40 (95.2%) showed improvement in histologic findings.
      CONCLUSION: CD is common among patients labeled as chronic diarrhea. In this
      subgroup, gluten-free diet may lead to a significant improvement in symptoms.
      Routine testing for CD may be indicated in all patients being evaluated for
      chronic diarrhea.

PMID- 15735485
TI  - Helicobacter pylori status and symptom assessment two years after eradication in
      pediatric patients from a high prevalence area.
AB  - OBJECTIVES: To establish the rate of Helicobacter pylori reinfection in children
      from an H. pylori high prevalence area, possible clinical features predictive of
      reinfection and the usefulness of re-treatment. METHODS: 65 consecutive children
      attending the authors' department between 1998 and 2000 who had proven successful
      H. pylori eradication were enrolled; 52 took part. Patients and family members
      were invited to undergo C-urea breath testing and to complete a simple
      questionnaire regarding symptoms and socioeconomic status. Patients with H.
      pylori reinfection were offered treatment; eradication was assessed by C-urea
      breath test 8 weeks after completion of treatment. RESULTS: Of 52 children, 15
      (28.8%) were H. pylori positive. Variables predictive of reinfection were age at
      primary infection and presence of an infected sibling. Although reinfected
      children were more frequently symptomatic than non-reinfected patients, no
      specific symptom was associated with reinfection. Of the nine re-treated patients
      who returned 8 weeks after completing therapy, the bacterium was eradicated in
      five (56%). CONCLUSIONS: The 12.8% per year reinfection rate in childhood at 2
      years that we observed should prompt a re-evaluation of H. pylori status even
      after a successful eradication. Living in an H. pylori high prevalence area
      increases the annual risk of reinfection by approximately fourfold over the
      annual risk in H. pylori low prevalence areas.

PMID- 15735486
TI  - Efficacy and safety of lansoprazole in adolescents with symptomatic erosive and
      non-erosive gastroesophageal reflux disease.
AB  - OBJECTIVES: To assess the efficacy and safety of lansoprazole in the treatment of
      adolescents with symptomatic, endoscopically proven, non-erosive gastroesophageal
      reflux disease and erosive esophagitis. METHODS: Adolescents between 12 and 17
      years of age with esophagitis were enrolled in this open-label trial and treated
      with lansoprazole 15 mg (non-erosive) or 30 mg (erosive) once daily for 8 weeks.
      If unhealed at week 8, those with erosive esophagitis were treated with an
      additional 4 weeks of lansoprazole 30 mg once daily. RESULTS: Lansoprazole
      produced a significant reduction from baseline in the median percentage of days
      with reflux symptoms (91 to 43% in the 64 adolescents with non-erosive disease
      and 85 to 16% in the 23 adolescents with erosive esophagitis, P < or = 0.001 for
      each comparison). At week 8, mucosal healing had occurred in 95% (21 of 22) of
      those with erosive esophagitis. Treatment-related adverse events were reported by
      19% of patients with non-erosive and 4% of patients with erosive esophagitis.
      Headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%) were the most
      frequently reported adverse events. One patient discontinued treatment early
      because of dizziness and vomiting. An elevation in mean serum gastrin from
      baseline (59 pg/mL at pretreatment to 80 pg/mL at final visit) was observed.
      CONCLUSION: Lansoprazole 15 mg or 30 mg once daily reduced symptoms of
      gastroesophageal reflux in adolescents with non-erosive gastroesophageal reflux
      disease and erosive esophagitis, respectively. Lansoprazole 30 mg once daily for
      8 weeks was effective in healing erosive esophagitis. Both treatment regimens
      were considered safe.

PMID- 15735487
TI  - Characteristics of human calicivirus enteritis in intestinal transplant
      recipients.
AB  - OBJECTIVES: The human caliciviruses, which include Norwalk-like viruses (or
      Noroviruses) and Sapporo viruses, commonly cause epidemic and endemic viral
      gastroenteritis of short duration in healthy individuals. However, the impact of
      human calicivirus in immunosuppressed populations has not been established. The
      authors report five pediatric patients who developed human calicivirus enteritis
      after intestinal transplantation. METHODS: Infection was documented with
      repetitive reverse transcription polymerase chain reaction testing with
      nucleotide sequencing of tissue and lumen fluid specimens. RESULTS: A single
      strain, type Miami Beach, affected all patients in the hospital with an apparent
      index case. A potential mode of transmission was not defined. Severe osmotic or
      secretory diarrhea necessitated intravenous fluid therapy for 40 days or more in
      three of the five infants. Concurrent or recent subclinical allograft infection
      with adenovirus in two patients was associated with more severe symptoms. Virus
      excretion exceeded 80 days in two patients. Differentiation of human calicivirus
      enteritis from allograft rejection was difficult, as both disorders were
      associated with increased enterocyte apoptosis and inflammation. Intensification
      of immunosuppressive therapy because of suspected rejection appeared to prolong
      symptoms. CONCLUSION: These findings demonstrate that human calicivirus can be a
      significant pathogen in intestinal transplant recipients and potentially in other
      immunocompromised patients.

PMID- 15735488
TI  - Attitudes toward percutaneous endoscopic gastrostomy placement in cystic fibrosis
      patients.

PMID- 15735489
TI  - Gastric emptying in premature newborns with acute respiratory distress.
AB  - OBJECTIVES: The authors hypothesized that acute respiratory distress (ARD) delays
      gastric emptying. The objective was to test this hypothesis by assessing gastric
      emptying on the second and seventh days of life in premature infants with ARD
      resulting from pulmonary disease. METHODS: Thirty-nine newborns with ARD starting
      on the first day of life were selected and paired with 39 healthy control
      newborns matched by weight (within 250 g). Gestational age was <or =35 weeks and
      birth weight was < or =1750 g for all subjects. Gastric emptying was assessed at
      48.0 +/- 24.0 hours and at 168.0 +/- 24.0 hours of life. A test meal consisting
      of 3 mL/kg of 5% glucose in water labeled with phenol red was administered by
      gastric tube over 1 minute and gastric retention was determined as percent test
      meal remaining in the stomach 30 minutes after administration. RESULTS: Gastric
      retention at 30 minutes varied considerably in both groups and was significantly
      higher (P < 0.01) in newborns with ARD (61.4%) than controls (51.8%) at 48.0 +/-
      24.0 hours, decreasing significantly after partial or full remission of ARD at
      168 +/- 24 hours of life. Gastric retention was 60.2% in newborns with feeding
      intolerance and 36.8% in tolerant newborns (P < 0.001) at 168 hours. ARD and
      periventricular or intraventricular hemorrhage were predictors of gastric
      retention at 48 +/- 24 hours of life, whereas feeding intolerance and gestational
      age were predictors of gastric retention at 168 +/- 24 hours. Gastric retention
      was inversely correlated with gestational age. CONCLUSION: Gastric emptying is
      delayed in premature infants with ARD during the first 72 hours of life and may
      impair the initiation of enteral feeding.

PMID- 15735490
TI  - The prevalence of encopresis in a multicultural population.
AB  - BACKGROUND: Population-based studies on the prevalence of encopresis in children
      are scarce and generally outdated. Prevalence estimates based on clinical studies
      are unreliable because parents tend to be reticent to seek medical help for this
      problem. Professional help is necessary, however, because encopresis can lead to
      serious psychosocial health problems. The authors examined the prevalence of
      encopresis in children, the frequency of visits made to general practitioners for
      encopresis and the psychosocial health problems of encopretic children. METHODS:
      This population-based study involved 13,111 parents and their 5- to 6-year-old
      children and 9,780 parents and their 11- to 12-year-old children, all residents
      of Amsterdam, the Netherlands. RESULTS: The prevalence of encopresis was 4.1% in
      the 5-to-6 age group and 1.6% in the 11-to-12 age group. Encopresis was more
      frequent among boys and children from the very depressed areas of the city.
      Encopresis was less frequent among Moroccan and Turkish children. A defecation
      frequency of less than three per week was found in 3.8% of the 5- to 6-year-olds
      and 10.1% of the 11- to 12-year-olds with encopresis. Only 37.7% of the 5- to 6
      year-olds and 27.4% of the 11- to 12-year-olds who had encopresis had ever been
      taken to see a doctor for this problem. Psychosocial problems were far more
      common among children with encopresis than among normal children. CONCLUSIONS:
      Encopresis is a common condition that is often associated with psychosocial
      health disorders but only a small proportion of the children with encopresis are
      taken to a general practitioner to discuss their problem.

PMID- 15735491
TI  - Laparoscopic antireflux procedures in the management of gastroesophageal reflux
      following esophageal atresia repair.
AB  - OBJECTIVES: The validity of open fundoplication after esophageal atresia (EA)
      repair is still disputed. The authors have retrospectively evaluated the results
      achieved in their centers using laparoscopic antireflux procedures (LARP) in
      children operated for EA at birth. METHODS: From 1998 to 2002, 350 children
      underwent LARP. Of these, 21 (6%) underwent EA repair at birth. Our study focused
      only on the management of these 21 patients; 5 of them (23.8%) were
      neurologically impaired children (NIC). All underwent LARP, 9 patients according
      to Nissen, 9 according to Thal, and 3 according to Toupet. The 5 NIC with feeding
      problems underwent concomitant g-tube placement during the same procedure.
      RESULTS: All the procedures were completed in laparoscopy, without intraoperative
      complications. The mean operative time was 65 minutes (range 45-140). We had no
      mortality in our series. Hospital stay varied from 2 to 9 days (median 3 days).
      At a maximum follow-up of 6 years, all patients were evaluated with a 24-hours pH
      metry and barium swallow. The 16 neurologically normal children were free of
      symptoms at the last follow-up; five of them (31.2%) had mild dysphagia, which
      disappeared spontaneously within 3-6 months. One girl experienced an important
      episode of aspiration 2 years after the LARP, although there was no evidence of
      reflux at the follow-up examinations. As for the 5 NIC, one patient eats only
      through a g-tube, the other 4 undergo mixed feeding (g-tube and mouth); none have
      signs of GER, but two of them still present respiratory symptoms, and one has
      delayed gastric emptying. CONCLUSIONS: In our experience laparoscopic antireflux
      surgery is an appropriate treatment of GER in children operated for EA at birth,
      independently of the antireflux mechanism adopted; the 31.2% rate of short-term
      dysphagia presenting as residual respiratory symptoms may be due to a primary
      dysmotility of the esophagus consequent to the esophageal atresia.

PMID- 15735492
TI  - Evidence for increased apoptosis of duodenal intraepithelial lymphocytes in cow's
      milk sensitive enteropathy.
AB  - OBJECTIVES: Enterocyte apoptosis induced by activated intraepithelial lymphocytes
      (IELs) is increased in celiac disease (CD). A lesser increment in intraepithelial
      lymphocytes associated with normal villous structure is also characteristic of
      cow's milk sensitive enteropathy (CMSE), but no information is available about
      the apoptosis rate of this condition. METHODS: Endoscopic biopsy samples of 21
      children with untreated CMSE were compared with samples from 15 children with CD
      and 18 controls. Apoptosis was analyzed using the TUNEL technique and the M30
      antibody from duodenal bulb and mid-duodenum samples. Ki-67 was used to detect
      the proliferation rate and CD3(+) to count the overall number of T lymphocytes.
      RESULTS: In the mid-duodenum, CMSE patients showed a significantly increased
      intraepithelial and lamina propria density of TUNEL(+) cells, but no difference
      in the density of M30(+) epithelial cells was seen compared with controls. In CD
      subjects, TUNEL(+) counts in mid-duodenal villous epithelium were increased.
      CD3(+) intraepithelial lymphocytes were increased in both CMSE and CD and
      correlated with TUNEL(+) and M30(+) counts among all patients. No increase in
      proliferation rate was seen in CMSE, and no significant correlations between
      apoptosis and proliferation rates were detected. CONCLUSIONS: The observed
      increase in TUNEL(+) counts and the absence of any increase in M30(+) cells
      suggest that the apoptosis rate of intraepithelial lymphocytes, but not of
      enterocytes, is increased in the small IELs in CMSE. However, the number of
      intraepithelial lymphocytes is still elevated in CMSE, indicating that a
      disturbance of homeostasis of intraepithelial lymphocytes is important in its
      pathogenesis.

PMID- 15735493
TI  - Shigella antibiotic resistance in central Turkey: comparison of the years 1987
      1994 and 1995-2002.
AB  - BACKGROUND: The epidemiology and antibiotic susceptibility of Shigella species
      changes over time. Updated susceptibility knowledge is necessary for appropriate
      empirical antibiotic treatment. METHODS: In this study the clinical
      characteristics and the antibiotic susceptibility test results of Shigella
      species isolated from patients admitted to Hacettepe University Ihsan Dogramac
      Children's Hospital Diarrheal Diseases Training and Treatment Unit between 1995
      2002 (n = 218) were evaluated. The results were compared with the results of 1987
      1994 from the same center (n = 618). RESULTS: The predominant species was S.
      sonnei in both periods with increasing prevalence in the later period (64% and
      71.5% respectively, P < 0.05). Although the prevalence of bloody diarrhea among
      Shigella cases did not change between periods, the prevalence of mild to moderate
      dehydration (11% and 20.6%) increased. Approximately 40% of cases were prescribed
      antibiotics on the suspicion of shigellosis. When the two periods were compared,
      Shigella resistance to trimethoprim/sulfamethoxazole increased from 39% to 70% (P
      < 0.0001), whereas resistance to ampicillin decreased from 41% to 23% (P <
      0.0001). However, the resistance of S. flexneri to ampicillin was found to be
      quite high (72.9%) between 1995-2002. No Shigella species resistant to
      ciprofloxacin was detected. Multi-drug resistance was present in 52 (24%) of the
      cases, of which 10 were S. sonnei (6.3%) and 42 S. flexneri (26.4%) (P < 0.0001).
      CONCLUSION: The need to treat all Shigella cases in areas where S. sonnei is
      predominant should be reevaluated, as should the appropriate empirical
      antibiotic.

PMID- 15735494
TI  - Multidisciplinary management of surgical disorders of the pancreas in childhood.
AB  - OBJECTIVES: To describe the frequency and range of pancreatic disorders in
      children requiring surgical intervention and to highlight the importance of
      multidisciplinary management. METHODS: An audit of all children under 17 years of
      age referred with surgical disorders of the pancreas or pancreatitis to a
      regional pediatric gastroenterology unit in the United Kingdom during a 10-year
      period. A retrospective chart review of clinical features, pathology and outcome
      was undertaken. RESULTS: Surgical intervention was required for the following
      pancreatic disorders: persistent hyperinsulinemic hypoglycemia of infancy (n =
      4), pancreatic tumors (n = 5), pancreaticobiliary malunion (n = 12), pancreatic
      trauma (n = 6) and pancreatitis (n = 10). The indications for surgery in acute
      pancreatitis were a persistent pseudocyst (n = 1) and treatment of an underlying
      cause of pancreatitis (n = 4); in chronic pancreatitis, surgery was used to treat
      symptomatic pancreatic duct strictures (n = 4). One child died of a progressive
      lymphoma but all others who underwent surgery are alive and well. All 33 children
      with acute pancreatitis, including four with pancreatic necrosis, survived.
      CONCLUSIONS: Surgery for pancreatic disorders in children is rarely required but
      may be necessary a) for definitive management of primary pancreatic pathology, b)
      to treat sequelae of acute or chronic pancreatitis and c) to treat an underlying
      cause of pancreatitis. There is a broad spectrum of potential pathologies. These
      patients are best managed by a multidisciplinary team approach.

PMID- 15735495
TI  - An unusual intestinal presentation of C-ANCA/PR-3 positive vasculitis in a child.

PMID- 15735496
TI  - Simultaneous herpetic and candidal esophagitis in an immunocompetent teenager.

PMID- 15735497
TI  - A case of neonatal hemochromatosis-like liver failure with spontaneous remission.

PMID- 15735498
TI  - Is there an association between duodenal atresia and choledochal cyst?

PMID- 15735499
TI  - Diagnostic role of upper gastrointestinal endoscopy in pediatric inflammatory
      bowel disease.

PMID- 15735500
TI  - Prebiotics: do they really change infant intestinal immunity?

PMID- 15735501
TI  - Does treating gastroesophageal reflux cause pneumonia?

PMID- 15735502
TI  - Another risk factor for neonatal hyperbilirubinemia.

PMID- 15735503
TI  - Topical nitric oxide treatment after pull through operations for Hirschsprung
      disease.
AB  - AIM: The diagnosis and treatment of Hirschsprung disease are well standardized.
      Symptoms of obstruction after surgery for Hirschsprung disease may result from
      residual spasticity of the internal anal sphincter. Nitric oxide (NO) is the
      chemical messenger mediating relaxation of the internal anal sphincter and its
      exogenous application results in a relaxation response in smooth muscle. The
      purpose of this study was to investigate topical NO application for obstructive
      symptoms after surgery for Hirschsprung disease and to correlate the symptoms
      with manometric findings with a view to directing further management. MATERIALS
      AND METHODS: The authors reviewed application of topical NO on six symptomatic
      children who were operated for Hirschsprung disease. Eighteen patients older than
      3 years of age were evaluated for anorectal manometric, functional and clinical
      outcome. The symptoms included enterocolitis in three patients and constipation
      in three patients. NO ointment was applied twice daily for 6 weeks in symptomatic
      patients and manometry was repeated. RESULTS: Anorectal manometric evaluation of
      six patients showed high internal anal sphincter tone without reflex relaxation
      on applying distending pressure to the rectum. Marked improvement of symptoms was
      noted after 6-week application of topical NO and maximal internal anal resting
      pressure decreased significantly (35% reduction). After ceasing application of
      topical ointment, increased maximal anal resting pressure was seen again.
      CONCLUSION: Although anal sphincter hypertonicity is not thought to be the only
      cause of post-operative obstructive symptoms, relaxation of the internal anal
      sphincter may improve the symptoms. Topical NO can be used for treatment of
      obstructive symptoms in Hirschsprung disease. We managed our symptomatic patients
      successfully with local NO application with a reversible chemical sphincterotomy.
      NO could be used as a therapeutic modality.

PMID- 15735504
TI  - Memorable medical mentors: X. Richard Wesley TeLinde (1894-1989).

PMID- 15735532
TI  - [The role of the von Willebrand factor in renal diseases and haemodialysis
      patients].
AB  - During a period of twenty years, the von Willebrand factor (VWf) biological
      activity was evaluated in 805 patients with vein thrombosis, diabetes mellitus,
      chronic renal failure and ischemic heart disease. The examined patients were 168
      with vein thrombosis, 129 with diabetes mellitus, 412 with chronic renal failure
      (CRF), and 96 with ischemic heart disease. The biological activity was also
      determined in 104 haemodialysis patients using four different haemodialytic
      membranes: 30 on cuprophan membrane, 30 on polymethylmetacrylate membrane (PMMA),
      24 on hemophane and 20 patients on polysulphone (PS) membrane. In 42 patients
      with arterio-venous fistula prone to thrombosis, the biological activity of the
      von Willebrand Factor was 178% in comparison to 106% in the control group. The
      biological activity of VWF was increased in patients with vein thrombosis (p <
      0.02), in patients with diabetes mellitus (p < 0.01), CRF (p < 0.05), and in
      patients with ischemic heart disease (p < 0.01). The highest biological activity
      was found in patients on PMMA (p < 0.001), then cuprophan (p < 0.05) and
      hemophane membrane (p < 0.01), while the lowest increase of its concentration was
      noticed in patients on PS without statistical significance. In arteriovenous
      fistula prone to thrombosis patients biological activity of the von Willebrand
      Factor was significantly increased (p < 0.01). Our investigations show the
      importance of VWF as a marker of endothelial disfunction, a possible predictor of
      A-V fistula thrombosis, and a possible marker of haemodialysis membranes
      biocompatibility.

PMID- 15735533
TI  - [Hypertension and diabetes mellitus].
AB  - AIM: To evaluate hypertension in patients with Diabetes Mellitus (DM) and its
      correlation with age, duration of DM, Body Mass Index (BMI) and HbA1C). MATERIALS
      AND METHODS: A retrospective study was made on 1211 patients with DM (male 554
      and female 657), hospitalized at Clinic of Endocrinology between January 2001 and
      December 2002. Patients were divided in two groups: Control group (CG)-subdivided
      into 3 groups patients with DM type 1 (CG-1), DM type 2 on oral anti-hyper
      glycemic agents (CG-2)and DM type 2 on insulin therapy (CG-3) and Examined Group
      (EG), the same groups for diabetes, including hypertension. RESULTS: We found
      hypertension in 12.6% patients with DM type 1, 30.5% in DM type 2 on oral anti
      hyper-glycemic agents and 33.4% in DM type 2 on insulin therapy. CONCLUSION:
      Hypertension is mostly presented in DM type 2 patients (33,4%), instead of 12.6%
      in DM type 1. There is statistical significance (p<0.05) between duration of DM
      in patients with and without hypertension.

PMID- 15735534
TI  - Options in uraemia therapy for diabetics with end-stage renal disease.
AB  - In many countries, diabetic renal disease has become, or will soon become, the
      single most common cause of end-stage renal disease (ESRD). End-stage renal
      failure (ESRF) in type-2 diabetic patients is increasing worldwide. Incidence of
      ESRF caused by diabetic nephropathy (DN) in 1996 in the USA was 41.7% and
      prevalence was 32.4%. ESRD and ESRF caused by DN was 10%, 5-15% in different
      haemodialysis centres in adults in the year 2000 in the Republic of Macedonia. In
      this review article we discuss options in uraemia therapy for diabetics with
      ESRD. Assessment and treatment of a diabetic with ESRD must be highly
      individualized. Haemodialysis (HD) has emerged as the most common treatment for
      all forms of renal failure including diabetic nephropathy. In diabetics patients
      with ESRD, dialysis is started early at creatinine clearance as high as 15-20
      ml/min, at serum creatinin levels as low as 3-5 mg/dl. The first choice of HD
      access in diabetics is an autologous a-v fistula of the Cimino-Brescia type. The
      A-V fistula should be created several months before starting HD when creatinine
      clearance is above 20-25 ml/min. When peritoneal dialysis (PD) is selected,
      advance planning should ensure that a suitable peritoneal catheter is in situ 2-4
      weeks before starting dialysis. HD procedures should be with low ultrafiltration
      rates and prolonged duration of dialysis sessions. The ultrafiltration in
      diabetics should not exceed more than 500-600 ml/h on HD. This means dialysis
      sessions of more than 4h and, in larger patients, of more than 5h HD three times
      per week. Renal transplantation (RT) is a safe and effective treatment modality
      for diabetic subjects with ESRD. Cardiovascular disease and serious infections
      are the major causes of death in haemodialysed and transplanted diabetics.
      Despite recent improvement, rehabilitation of HD diabetics continues to be
      inferior to that of non-diabetics. Improvement of survival is a matter of
      reduction of cardiovascular death and infection.

PMID- 15735535
TI  - [Inadequate erythropoietin production (epo) in patients with multiple myeloma].
AB  - Anaemia is the most common haematological complication in patients with malignant
      diseases. It is found in 60%-90% of cases with multiple myeloma. The pathogenesis
      of this hypoproliferative, normochromic, normocytic anaemia is complex. Results
      from clinical studies which evaluate the efficacy of recombinant human
      erythropoietin (rHuEpo) refer to the possibility that patients with multiple
      myeloma independently of renal function could have Epo deficiency. Based on this
      finding, the aim of the study was to evaluate the erythropoietin production in
      patients with multiple myeloma in order to define clinical conditions of Epo
      deficiency and thereby enable rational use of this expensive drug. 42 patients
      with multiple myeloma were examined. The control group consisted of 25 patients
      with iron deficiency anaemia. 14 healthy volunteers represented the so-called
      "normal" control. The adequacy of Epo production was estimated from the graphic
      representation of the linear regression between Epo and haemoglobin (Hb) in the
      control group, as well as from O/PEpo ratio as a measure of the degree of
      adequacy of Epo production (O -- observed Epo value, P -- predicted Epo value
      from the regression equation of the control group). The erythropoietic activity
      was estimated from the graphic representation of the linear regression between
      soluble transferin receptors (sTfR) and Hb in the control group, as well as from
      O/PsTfR ratio, as a measure of the degree of adequacy of erythropoietic activity
      (O -- observed sTfR value, P -- predicted sTfR value from the regression equation
      of the control group). Significant inverse correlation between Epo and Hb was
      found in patients with multiple myeloma but preserved renal function, which was
      not the case in patients with renal insufficiency. 43% of patients without renal
      insufficiency and 85% of patients with renal insufficiency had inadequate Epo
      response to anaemia. In both patient groups (with and without renal
      insufficiency) instead of the expected inverse relationship between Hb and sTfR
      as in the control group, a positive correlation was found. 76% of patients had
      inadequate sTfR response to anaemia. There is a positive correlation between
      O/PEpo and O/PsTfR which is in favour of Epo driven erythropoiesis. O/PEpo and
      O/PsTfR in patients with multiple myeloma are significantly lower in comparison
      to the control group, which also points to the inadequacy of erythropoietin
      production, respectively erythropoietic activity. In conclusion, the results from
      this study show unambiguously that anaemia in patients with multiple myeloma
      appears because of decreased erythropoiesis as a consequence of bone marrow
      infiltration with malignant plasma cells as well as inadequate Epo production.
      Most probably, there are two forms of inadequate Epo production: one because of
      the renal insufficiency and the other that found in patients with anaemia of
      chronic diseases the mechanism of which is not clear.

PMID- 15735536
TI  - [Tracking the changes in the HDL cholesterol levels at different time intervals
      after acute myocardial infraction].
AB  - Low HDL cholesterol level in the blood increases the risk of unwanted coronary
      events in patients with verified CAD, which can be considerably decreased by
      appropriate and on-time application of pharmacologic and non-pharmacologic
      therapeutical measures. Numerous studies have shown that the level of the serum
      lipids, measured in the first 24 hours of the acute myocardial infarction, in
      fact is the basal lipid level, which is liable to changes immediately after the
      event, and gets back to its initial (basal) value within the next 6-12 weeks. In
      order to confirm if there are changes in the lipid profile and what they look
      like, particularly the HDL cholesterol in the blood, in 230 middle aged patients
      (59.87 +/- 13 years old), mostly males (66.5%) with ST-elevation acute myocardial
      infarction (STEMI), a follow-up of the HDL cholesterol level was performed, taken
      from the vein blood and determined by standard enzymatic methods at different
      time intervals after the actual event (24 hours, 3-7 days, 10-14 days, 30-60
      days, 60-90-days) was performed. The results acquired showed that the patients
      with STEMI had a lower initial HDL cholesterol level, which showed a tendency to
      decrease three days after the actual event, and to be gradually "normalized"
      after 60-90 days, i.e. not only turning back the HDL cholesterol values to the
      initial level, but their overcoming too. It is interesting to mention, that the
      average value of HDL cholesterol level in the blood, checked after 60-90 days
      after the actual event, is overcoming that basal value in a positive sense, but
      it was further on higher than the desired aim of 40 mg/dl (1.03 mmol/l). From the
      results of our follow-ups, we can conclude that the optimal time for determining
      the HDL cholesterol level in the blood in patients with STEMI, are the first 24
      hours of the actual event, since in the first 24 hours there is a relevant
      decrease of the HDL cholesterol level in the blood. The values of the lipid
      profile acquired at that period, should be considered as basal.

PMID- 15735537
TI  - Bone biopsy in the diagnosis of renal osteodystrophy.
AB  - When renal disease develops, mineral and vitamin D homeostasis is disrupted,
      resulting in diverse manifestations in bone cells and structure as well as the
      rate of bone turnover. In ESRF when patients require chronic maintenance
      dialysis, nearly all of them have abnormal bone histology named renal
      osteodystrophy (ROD). On the other hand, survival rates of patients on dialysis
      have increased with improved dialytic therapy and the resultant increased
      duration of dialysis has led to a rise in renal osteodystrophy. Because this
      metabolic bone disease can produce fractures, bone pain, and deformities late in
      the course of the disease, prevention and early treatment are essential. Serum
      PTH levels are commonly used to assess bone turnover in dialyzed patients.
      However, it is found that serum PTH levels between 65 and 450 pg/ml seen in the
      majority of dialysis patients are not predictive of the underlying bone disease.
      To date, bone biopsy is the most powerful and informative diagnostic tool to
      provide important information on precisely the type of renal osteodystrophy
      affecting patients, the degree of severity of the lesions, and the presence and
      amount of aluminum and strontium deposition in bone. Bone biopsy is not only
      useful in clinical settings but also in research to assess the effects of
      therapies on bone. Although considered as an invasive procedure, bone biopsy has
      been proven as safe and free from major complications besides pain, haematoma or
      wound infections, but the operator's experience and skill is important in
      minimizing morbidity. Alternatives to bone biopsy continue to be pursued, but the
      non-invasive bone markers have not been proven to hold sufficient diagnostic
      performance related to the bone turnover, mineralization process and bone cell
      abnormality. At present however, the transiliac bone biopsy remains the golden
      standard in the diagnosis of renal osteodystrophy.

PMID- 15735538
TI  - The influence on coagulation of transdermal estrogen hormone replacement therapy
      as a preoperative preparation of the tissue before vaginal hysterectomy.
AB  - In 32 postmenopausal patients who underwent vaginal hysterectomy due to the
      presence of uterine prolapse at the Department of Uro-gynaecology and Pelvic
      Floor Disorders in the Clinic of Gynaecology and Obstetrics, Medical School,
      Skopje in the period from 1st January 2002 to 1st January 2003, and who were
      preoperatively treated with transdermal estradiol 50 microg/day during 14 days
      the following parameters of the coagulating status were estimated: prothrombin
      time (PT) that is expressed in: absolute value, percentage and INR; activated
      partial thromboplastin time (aPTT Pathrombin SL); thrombin time and platelets
      number before and after hormone replacement therapy. After 14-day transdermal
      estrogen therapy, the parameters: PT, PT%, PT INR, aPTT Pathrombin SL didn't
      expressed significant changes, the thrombin time expressed significant extension,
      and the platelets expressed a significant decrease. According to our results, the
      transdermal estrogens might not have any influence on the hepatic synthesis of
      coagulating factors till the step of prothrombin formation. They might have an
      essential influence on the step of prothrombin transformation into thrombin, as
      well as on the process of megacaryocytes segregation into platelets.

PMID- 15735539
TI  - Child trauma, attachment and biofeedback mitigation.
AB  - The aim of this study is to investigate the correlation between the quality of
      attachment in early infancy and the effects of child trauma, as well as to
      introduce some innovative therapeutic approaches. For this reason, a group of 10
      children manifesting post-traumatic stress disorder (PTSD), diagnosed by ICD-10,
      was selected. The mean age of the patients was 9 +/- 3.05 years, from both sexes
      (girls 3, boys 7). Mothers and children were examined by a battery of
      psychometric instruments Minnesota Multiphasic Personality Inventory (MMPI),
      Child Behaviour Checklist (CBCL), Eysenck Personality Questionnaire (EPQ), and
      State Anxiety Inventory (STAI). In addition to the classical psychotherapeutic
      methods (supportive, behaviour and play therapy), the multimodal computerised
      biofeedback technique was introduced for both assessment and therapy. The results
      for the children showed a high level of anxiety and stress, somatisation and
      behavioural problems (aggressivity, impulsivity, non-obedience, and nightmares),
      complemented by hypersensitive and depressive mothers and miss-attachment in the
      early period of infancy. Consequently, the explanation of the early
      predisposition to PTSD was related to be the non-developed Right Orbitofrontal
      Cortex-ROFC. The latter resulted from insecure attachment confirmed in all the
      children examined. The therapeutic results obtained with biofeedback techniques
      are very encouraging.

PMID- 15735540
TI  - Applications of the oral scraped (exfoliative) cytology in oral cancer and
      precancer.
AB  - Scraped (exfoliative) cytology is a simple and harmless procedure, which has been
      a controversial technique according to its real validity in oral pathology.
      Lately it has re-emerged due to its application in oral precancer and cancer as a
      diagnostic and predictive method as well as for monitoring patients. New
      diagnostic techniques have been developed, such as "brush biopsy" and multiple
      molecular studies using the cells collected. In this review we are going to
      analyse the more novel aspects related with the applications of the scraped or
      exfoliative cytology in oral precancerous and cancerous pathology, specially
      focusing on molecular studies and their diagnostic and prognostic implications.

PMID- 15735541
TI  - Cytological characteristics of acinic cell carcinoma (ACC) diagnosed by fine
      needle aspiration biopsy (FNAB). A study of four cases.
AB  - OBJECTIVE: To present the cytopathological characteristics of acinic cell
      carcinoma (ACC) as well as its cyto-histological correlation, commenting on the
      differential diagnostic problems of this entity based on four observations
      studied using fine-needle aspiration biopsy (FNAB). CLINICAL CASES: Two males of
      52 and 53 years of age, one 79 year-old woman and a girl of 12 years of age, who
      presented tumors located in the parotid area (cases 1, 2 and 4) and at the
      laterocervical level (case 3). In 3 patients, the FNAB was, together with the
      image studies, the first diagnostic indication; case 3 corresponding to a
      puncture of metastatic laterocervical adenopathies in a patient with a history of
      parotid ACC. CYTOLOGICAL FINDINGS: The cytologic smears revealed abundant tumoral
      cellularity arranged in small monolayered sheets, forming acinar structures or
      isolated cells. The abundance of bare nuclei at the background of the smears, and
      the absence of adipose tissue and ductal epithelium are highlighted. The cells
      possessed round or oval monomorphic nuclei, few nucleoli and abundant granular or
      finely vacuolate cytoplasm. DISCUSSION: FNAB provides essential information on
      the diagnostic-therapeutic management of salivary gland tumors; this methodology
      is highly sensitive in its diagnostic efficacy. The diagnosis of ACCs frequently
      presents difficulties, owing to the great cytologic similarity of the tumor cells
      with the normal acinar component of the salivary gland. The differential
      diagnosis is considered, fundamentally, with clear cell carcinomas,
      mucoepidermoid carcinomas, Warthin s tumor, and oncocytomas. Our observations
      confirm the validity of FNAB in a first diagnostic approximation for those
      lesions accessible to direct puncture.

PMID- 15735542
TI  - Lingual ulcer as the only sign of recurrent mycobacterial infection in an
      HIV/AIDS-infected patient.
AB  - The report describes an HIV/AIDS patient seen at a referral center in Mexico
      City, in whom a mycobacterial infection in the oral mucosa, probably tuberculosis
      (TB) was identified. The purpose is to describe the clinical and histological
      findings in an HIV-infected patient, who after being treated successfully for
      tuberculous lymphangitis 4 years ago, presented with a lingual ulcer as the only
      suggestive sign of recurrence of mycobacterial infection, probably M.
      tuberculosis. A 39-year-old man seen in the HIV clinic of the Instituto Nacional
      de Ciencias Medicas y Nutricion "Salvador Zubiran" in Mexico City since 1991 for
      HIV infection. In 1999 the patient developed tuberculous lymphangitis; he was
      managed with a 4-drug regimen for 12 months, with improvement of local and
      systemic symptoms. In May of 2003, the patient presented a painful superficial
      lingual ulcer, 0.7 cm in diameter, well circumscribed, crateriform with slightly
      elevated, irregular and indurated borders, of 4 months duration. The
      histopathological examination showed chronic granulomatous inflammation with
      giant multinucleated cells, suggestive of mycobacterial infection, and recurrence
      of TB was considered. Rifampin, isoniazide, pyrazinamide, ethambutol and
      streptomycin were administered. The lingual lesion improved with partial healing
      at the first week and total remission at 45 days after the beginning of the
      antituberculous treatment. In June, 2003, the patient began highly active
      antiretroviral therapy (HAART) that included two NRTIs and one NNRTI. At 7 months
      of follow-up, the patient remains free of lingual lesions. The particularity of
      the present case is that the lingual ulcer was the only sign of infection by
      mycobacteria, suggestive of TB, in an HIV/AIDS patient that probably represented
      a recurrence of a previous episode.

PMID- 15735544
TI  - Rhomboid glossitis in atypical location: case report and differential diagnosis.
AB  - Median rhomboid glossitis (MRG) is an uncommon benign abnormality of the tongue,
      most frequently affecting men. It is typically located around the midline of the
      dorsum of the tongue, anterior to the lingual "V", appearing as a reddish,
      rhomboid area, depapillated, flat maculate or mamillated and raised by 2 - 5 mm.
      This paper reports a case of rhomboid glossitis in a 61-year-old man who
      consulted for a painless raised lesion on the dorsum of the tongue, in left
      paramedial (not medial) location. Histopathological findings were compatible with
      rhomboid glossitis. Other diagnoses considered but ruled out on the basis of the
      clinical and histopathological findings were haemangioma, pyogenic granuloma,
      amyloidosis, granular cell tumour, and squamous cell carcinoma. This case
      confirms that rhomboid glossitis may occur in paramedial locations.

PMID- 15735543
TI  - Liquid-based preparations versus conventional cytology: specimen adequacy and
      diagnostic agreement in oral lesions.
AB  - OBJECTIVE: To compare specimen adequacy and diagnostic agreement between liquid
      based preparations and conventional smears in oral lesions, and to test the
      viability of immunocytochemical assay in liquid-based preparations from oral
      carcinoma lesions. MATERIAL AND METHODS: Samples were collected from 44 patients.
      Conventional smears were prepared first, using a cytobrush device. Then the
      brush, containing the residual material, was immersed in a preservative fluid.
      The sample in the preservative fluid was processed according to the manufacturer
      directions (AutoCyte, Inc. Elon College, North Carolina, USA). Slides of both
      techniques were stained by Papanicolaou method. For immunocytochemical assay, a
      cytokeratin pool AE1/AE3 (Dako, CA, USA) was applied in liquid-based preparations
      from oral carcinoma lesions following the Streptavidin-biotin-peroxidase method.
      Fisher's exact test was used; significance was set for P < or = 0.05. RESULTS:
      Both techniques agreed on cytologic diagnosis in every case they yielded an
      adequate specimen; in 3 cases conventional smear resulted in hypocellularity and
      therefore inadequate for analysis. On specimen analysis, the liquid-based
      cytology demonstrated a statistically significant, 41% overall improvement in
      smear thickness and 66% in cell distribution (P < or = 0.05), and a reduction in
      cell overlapping and presence of blood (P < or = 0.05). The cell morphology was
      better visualized in the liquid-based preparations. The immunocytochemical assay
      reactions were positive in all malignant cases, the visualization of the
      immunostained cells being especially clear. CONCLUSION: Both, the liquid-based
      preparation and conventional smear, are diagnostically reliable; the liquid-based
      method showed an overall improvement on sample preservation, specimen adequacy,
      visualization of cell morphology and reproducibility.

PMID- 15735545
TI  - Focal epithelial hyperplasia. A rare disease in our area.
AB  - Focal epithelial hyperplasia is a benign, asymptomatic disease, occurring with
      very low frequency within our population. It appears as papules, principally on
      the lower lip, although it can also be found on the retro-commissural mucosa and
      tongue, and less frequently on the upper lip, gingiva and palate. We present the
      clinical case of a 9-year-old Saharan girl with lesions that clinically and
      histologically corresponded to a focal epithelial hyperplasia.

PMID- 15735546
TI  - Periodontal aspects in menopausal women undergoing hormone replacement therapy.
AB  - AIMS: Currently, an important number of women use HRT to control their hormonal
      problems during menopause. A large percentage of these have problems at
      periodontal level. The present study aims at examining the effects that
      menopause, due to a decline in the synthesis of hormones, mainly of estrogens,
      can cause on the oral dental health of such women; in particular on the
      characteristics of the gingiva and periodontium, checking whether characteristics
      such as gingival recession, pain, tooth mobility and periodontal pocket formation
      might permit physicians to evaluate the degree of bone loss in menopausal woman.
      PATIENTS: Menopausal women aged 40 to 58 years of age undergoing hormone
      replacement therapy that had gingival periodontal disturbances. The total
      population of the study comprised 210 patients, divided into two groups. One
      group received HRT administered in patches and the other group did not receive
      this therapy. METHOD: Gynecologic and odonto-stomatologic protocols were
      established for data collection. In order to assess the efficacy of the treatment
      a descriptive statistical study for sociodemographic variables, analysis of
      variance, McNemar's test and the Stuart-Maxwell test were performed. RESULTS: The
      mean age of the patients studied was 49.6 years. HRT acts as a protective factor
      in dental pain and improves tooth mobility and depth of the probing of
      periodontal pockets. With respect to the variable gingival recession, no
      significant results were found either for the group not receiving HRT or for the
      group being treated with patches. CONCLUSIONS: The response to the HR therapy in
      periodontal disease is probably due to the existence of estrogen receptors
      localized in the gingiva and in the periodontal ligament.

PMID- 15735547
TI  - Systemic conditions associated with periodontitis in childhood and adolescence. A
      review of diagnostic possibilities.
AB  - The term periodontitis is used to describe a group of multifactorial diseases
      that result in the progressive destruction of the structures that support the
      teeth within the jaws, the so-called attachment apparatus, which includes the
      periodontal ligament, cementum and alveolar bone. If left untreated, this process
      can ultimately lead to tooth loss. The pathogenesis of these diseases involves
      the initial colonization of the gingival microenvironment of a susceptible host
      by pathogenic bacteria found in dental plaque. Subsequently, much of the tissue
      destruction characteristic of periodontitis is a , by-product, of the host
      response directed against these organisms. One of the major factors that appear
      to modulate disease severity is systemic health. Severe periodontitis in young
      individuals can therefore be a manifestation of an underlying systemic disease.
      In this review we will discuss the most important systemic diseases that should
      be considered in a differential diagnosis when evaluating a pediatric patient
      presenting with periodontitis.

PMID- 15735548
TI  - Removal of hyperplastic lesions of the oral cavity. A retrospective study of 128
      cases.
AB  - AIMS: Based on our accumulated experience, the present study evaluates and
      discusses the indications, advantages and inconveniences of oral cavity epulis
      resection using the carbon dioxide laser (CO2) versus the Erbium:YAG laser
      (Er:YAG), diode laser and surgical scalpel. MATERIAL AND METHODS: A retrospective
      study has been made of 120 patients involving the removal of 128 epulis lesions
      with the CO2 laser, Er:YAG laser, diode laser and surgical scalpel. Postoperative
      controls were carried out after 7, 15 and 30 days to evaluate healing and wound
      evolution, and after 3, 6 and 12 months to assess possible relapse. RESULTS: Two
      groups were defined, based on the clinical and etiopathogenic characteristics of
      the excised lesions: gingival hyperplastic lesions (77 cases) and fibromatous
      hyperplasia (51 cases). The lower jaw was the most frequent location of gingival
      hyperplasia (51.9%). Fibrous hyperplasia was the most common histological
      diagnosis (49 cases; 63.6%). Percentage relapse following removal was 9.1%, of
      which 5 cases corresponded to fibrous hyperplasia. Only one malignancy was
      identified, corresponding to infiltrating squamous cell carcinoma. On the other
      hand, of the 51 treated cases of fibromatous hyperplasia, 58.8% were located in
      the upper jaw. These were histologically confirmed to be fibrous hyperplasia,
      with relapse in 19.6% of the cases. CONCLUSIONS: Although the different surgical
      techniques used for removal of epulis of the oral cavity are appropriate, we
      consider the CO2 laser to be the treatment of choice, since it offers a number of
      both intra- and postoperative advantages. On the other hand, all oral lesions
      require histological study to establish a firm diagnosis.

PMID- 15735549
TI  - Implants in anatomical buttresses of the upper jaw.
AB  - The skull presents a series of dense bony buttresses that conform a protective
      frame around the different craniofacial cavities. The middle third portion
      presents two anterior buttresses (frontomaxillary and frontozygomatic) and a
      posterior buttress (pterygomaxillary). In certain situations these structural
      supports allow the rehabilitation of free upper extremities in atrophic jaws by
      positioning parasinusal angulated implants--thereby avoiding the need for more
      complex reconstruction techniques such as sinus lifting or autografting
      procedures. The present study presents a review of the literature on implant
      insertion in anatomical buttresses of the upper jaw.

PMID- 15735550
TI  - Brown tumor of the mandible as first manifestation of primary
      hyperparathyroidism: diagnosis and treatment.
AB  - Brown tumor is one of the lesions that develop in patients with
      hyperparathyroidism. Any of the skeletal bones can be affected including the
      cranio-maxillofacial ones. Most of the times the brown tumor appears after a
      final diagnosis of hyperparathyroidism is made. However brown tumor can be the
      first clinical sign of the disease. A clinical case in which a brown tumor
      located in the anterior part of the mandible appears as the first sign of primary
      hyperparathyroidism is presented. The possible differential clinical diagnosis
      and the recommended treatments are revised.

PMID- 15735551
TI  - A Stafne's cavity with unusual location in the mandibular anterior area.
AB  - The typical Stafne's cavity, located on the posterior portion of the mandible, is
      a relatively uncommon entity. However, when the defect is located in the anterior
      region of the mandible, it is quite rare, having thus far been described in only
      36 cases in the scientific literature. Most of these defects appear in the fifth
      and sixth decades of life, are localized to the area of the canines and
      premolars, and have a predilection for males. The inferior dental canal, one of
      the anatomical-radiographic landmarks that aid in the diagnosis of Stafne's
      cavity in the posterior region, is rarely present anterior the mental foramen.
      For this reason, because of its more variable radiographic appearance compared to
      the posterior defect, its tendency to be superimposed over the apices of the
      teeth, and the rarity of its localisation to the anterior mandible, it is much
      more difficult to establish a definitive diagnosis of a Stafne's cavity in this
      location. It is therefore more likely that a diagnostic error can occur,
      especially early on. We present a new case in a 68-year-old male in which the
      diagnosis was serendipitous, and we review in particular the aetiology and
      pathogenesis, clinical aspects, and differential diagnoses for this condition.

PMID- 15735552
TI  - Submaxillary gland mucocele: presentation of a case.
AB  - The term mucocele is referred to two concepts: the extravasation cysts resulting
      from salivary glandular duct rupture, with mucin leakage into the surrounding
      peri-glandular soft tissue, and the retention cysts, caused by a glandular duct
      obstruction and resulting in a decrease or even an absence of glandular
      secretion. Mucocele can not be considered as a true cyst because its wall lacks
      an epithelial lining. These lesions are very common in the minor salivary glands
      (particularly in the labial glands), but are very infrequent in the major
      salivary glands--including the submaxillary glands. The present study describes a
      clinical case of a right submaxillary gland mucocele resolved by surgical
      treatment and reviews the differential diagnosis with other clinical entities.

PMID- 15735553
TI  - Langerhans's cell histiocytosis.
AB  - A 42 year-old male, smoker, was referred for evaluation of an ulcer located in
      the gingiva, during one month, that produced disturbances. On the intraoral
      examination we appreciated an ulceration of 0.5 cm, on a mandibular torus, in the
      lingual gingiva of the left first molar (Fig. 1-2). A panoramic x-Ray (Fig. 3), a
      CT scan (Fig. 4) and a biopsy were taken (Fig. 5-6, Fig. 6 is a S-100 stain).

PMID- 15735554
TI  - Pleomorphic adenoma of the palate.
AB  - An 82-year-old female with a history of high blood pressure and anorexia. She was
      referred for a long-evolving, asymptomatic large tumor (3x3 cm) on the right side
      of the palate (fig 1). The patient was wearing total dentures. Intraoral
      examination revealed a pediculate tumor of the same color as the adjacent mucosa
      and presenting a firm consistency. An MRI study (fig 2-3) and biopsy were carried
      out (fig 4-6).

PMID- 15735555
TI  - Peripheral ameloblastoma.
AB  - A 73-year-old male ex-smoker of 10 cigarettes/day (up until 10 years ago) with a
      history of hypertension treated with Diovan 80 (Valsartan) was referred by his
      dentist. For the past 6 months the patient has presented an ulcer located in the
      right retromolar trigone region. In the last 2 months the patient has used
      chlorhexidine rinses, and is not wearing his dentures; the lesions fail to heal,
      however. Intraoral examination showed an ulcer in the right retromolar trigone
      area (Fig. 1-2), with a fibroelastic consistency. No regional lymph nodes were
      palpable. A panoramic X-ray study (Fig. 3), biopsy (Fig. 4-6) and CT exploration
      were requested.

PMID- 15735556
TI  - Metallothionein overexpression does not protect against inflammatory bowel
      disease in a murine colitis model.
AB  - BACKGROUND: We evaluated whether modulation of metallothionein (MT, and
      subsequent oxidative stress) would influence the development and progression of
      colitis. MATERIAL/METHODS: MT-transgenic (MT-TG), MT-knockout (MT-KO), and wild
      type (WT) mice were treated with Dextran Sodium Sulfate (DSS) to induce colitis
      compared to controls (no DSS). RESULTS: The DSS treated MT-TG and MT-KO mice
      responded in a manner similar to that of DSS treated WT mice, with all groups
      developing severe colitis. The colonic MT content in DSS treated animals
      increased drastically when compared to controls. The colonic and blood levels of
      the antioxidant, glutathione (GSH), were significantly reduced in DSS treated MT
      TG and MT-KO mice. Howevei there was no significant difference in the cysteine
      levels in these mice. The subeellular level of MT was highest in intestinal
      crypts loci of MT-TG mice and was not observed in MT-KO mice as well as in the
      inflammatory lesions. CONCLUSIONS: We conclude that MT does not appear to
      influence the development or progression of intestinal pathology in the DSS
      animal model of IBD.

PMID- 15735558
TI  - TGF-beta3 inhibits pentagastrin-stimulated gastric acid secretion in rats.
AB  - BACKGROUND: Transforming growth factor beta3 (TGF-beta3) has been shown to
      accelerate gastric ulcer healing in rats. However, little is known about the
      mechanism. In this study we investigated the influence of TGF-beta3 on gastric
      acid secretion, since gastric hyperacidity is a major cause of gastroduodenal
      ulcer disease. MATERIAL/METHODS: Male Sprague Dawley rats were equipped with
      gastric Thomas cannulas and jugular vein catheters. The acute effect of either
      intravenous TGF-beta3 (400 and 1200 pg/kg/h) or saline (0.15 M) on pentagastrin
      stimulated (10 pg/kg/h) gastric acid secretion was evaluated by gastric acid back
      titration after 5 days of recovery. Additionally, pentagastrin-stimulated gastric
      acid secretion was assessed after 48 hours following TGF-beta3 (1200 microg/kg/h)
      or saline treatment. RESULTS: Pentagastrin significantly increased gastric acid
      production. TGF-beta3 significantly reduced pentagastrin-stimulated gastric acid
      secretion in a dose-dependent manner as early as 15 minutes after application
      (saline: 124.9+/-14.9 microEq H+/15 min, TGF-beta3: 97.7+/-13.1 9 microEq H+/15
      min, p<0.002). Additionally, pretreatment with TGF-beta3 abolished the effect of
      pentagastrin on gastric acid production. This effect lasted throughout the entire
      recording period of 48 hours. However, baseline physiological gastric acid
      production was not altered by TGF-beta3. CONCLUSIONS: TGF-beta3 inhibits gastric
      acid secretion when given prior to as well as after pentagastrin treatment. This
      implicates both a preventive and a therapeutic role of TGF-beta3 in
      gastroduodenal ulcer disease.

PMID- 15735557
TI  - Role of 5-HT1A and 5-HT1B receptors in the hypophagic effect of 5-HT on the
      structure of feeding behavior.
AB  - BACKGROUND: Feeding behavior is deeply affected by serotonergic
      neurotransmission. This regulatory activity is mediated mainly by specific 5
      HT1/2 receptors, and the paraventricular nucleus (PVN) plays a key role in this
      phenomena. In order to reveal the involvement of 5-HT1A and 5-HT1B receptors in
      the paraventricular nucleus of the hypothalamus (PVN) on serotonin-induced
      hypophagia, we examined the effects of intra-PVN injections of serotonin in WAY
      100635 or SB 216641-pretreated rats on the structure of feeding behavior.
      MATERIAL/METHODS: Male Wistar rats were kept at 21+/-1 degrees C with a 12 h
      light /dark cycle on a self-selection feeding paradigm, provided with freely
      available and separate sources of protein, carbohydrate, fat and water. Blockade
      of 5-HT1A or 5-HT1B receptors in the paraventricular nucleus was effected by WAY
      100635 (2 microg) or SB-216641 (2 microg) pretreatment; ten minutes later, 5-HT
      (2 microg) was applied into the same nucleus, then food intake and meal patterns
      were measured in a 30-minute period. The behavioral test was conducted at the
      beginning of the dark phase. RESULTS: The suppressive effect of 5-HT on
      carbohydrate intake was blocked by both WAY 100635 and SB 216641 at the beginning
      of the active (dark) feeding period. CONCLUSIONS: The hypophagic effect induced
      by 5-HT requires activation of 5-HT1A and 5-HT1B receptors, and the specific
      contribution of these subtype receptors is different, since the 5-HT1A subtype
      showed higher behavioral selectivity.

PMID- 15735559
TI  - Co-localization of human herpes virus 6 and tissue plasminogen activator in
      multiple sclerosis brain tissue.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the
      central nervous system of unknown etiology. Several viruses have been suggested
      as playing a role in the pathogenesis of MS. The aim of this study was to
      investigate the interrelationship of human herpesvirus 6 (HHV-6) and plasminogen
      activation at the cellular level in MS plaques. MATERIAL/METHODS: Brain tissue
      specimens obtained from autopsies of 15 patients with MS and 10 controls were
      studied immunohistochemically for HHV-6 and cytomegalovirus (CMV) antigen and
      tissue plasminogen activator (tPA) protein. The presence of Ebstein-Barr virus
      (EBV) EBER RNA was studied using RNA in situ hybridization. RESULTS: HHV-6
      antigen was identified in the cells of 67% (10/15) of MS brain sections and 30%
      (3/10) of the control sections. All samples were negative for CMV antigen and all
      samples with intact RNA were negative for EBV EBER RNA as demonstrated by in situ
      hybridization. tPA expression was found to be increased in MS plaques compared
      with the control samples. Interestingly, in 5 MS samples both HHV-6 antigen and
      tPA stained clearly, compared with none in the controls, but HHV-6 and tPA only
      occasionally co-localized in the same cells. CONCLUSIONS: At the cellular level,
      HHV-6 and plasminogen activation seem to co-localize in MS.

PMID- 15735560
TI  - The effects of carbenoxolone on spatial learning in the Morris water maze task in
      rats.
AB  - BACKGROUND: High-frequency oscillations (ripples) are proposed to be involved in
      memory consolidation. Ripple oscillations persist in the absence of chemical
      synaptic transmission and inhibitors of gapjunctions were shown to block high
      frequency oscillations in hippocampal slices. In this study we investigated the
      effects of carbenoxolone, as a gap-junction blocker, on spatial learning in the
      rat. Cognitive performance was assessed using the Morris water maze (MWM).
      MATERIAL/METHODS: Adult male rats were bilaterally cannulated into the CA1 region
      of their hippocampus. Carbenoxolone (1.23, 2.46, 4.92 microg/side), scopolamine
      (3 microg/side), and saline were injected through the cannulas before 4
      consecutive training trials and one test trial that conducted 24 h after the
      training trials with the platform removed. RESULTS: The results showed that
      carbenoxolone could significantly reduce the percentages of time spent, distance
      traveled, and entry into Q2 (the target quadrant) compared with the control
      group. The carbenoxolone group failed to use a selective search strategy during
      the final test trial, in which the platform was removed. CONCLUSION: The results
      of this study suggest that carbenoxolone as a gap-junction channel blocker can
      decelerate the learning performances of rats in a spatial memory task, such as
      the MWM, that requires the integrity of the hippocampus.

PMID- 15735561
TI  - Updated management of non-st-segment elevation acute coronary syndromes:
      selection of patients for low-cost care: an analysis of outcome and cost
      effectiveness.
AB  - BACKGROUND: The management of patients with acute coronary syndromes without ST
      segment elevation (NSTEACS) in a chest pain unit (CPU) should represent a cost
      effective advantage over conventional management in a coronary care unit (CCU).
      However, the safety and advantages of this approach are still unresolved.
      MATERIAL/METHODS: Outcomes and management costs were evaluated in patients with
      NSTEACS with intermediate-high TIMI risk scores (> or =3) randomized to receive
      management in a CPU or a CCU. Coronary events (CEs: angina, myocardial
      infarction, and death), revascularization, and resource utilization were compared
      between the two groups during hospital stay and at 6 months. RESULTS: Two hundred
      and ten patients were enrolled, 104 in the CPU and 106 in the CCU group. CEs were
      similar in both groups both during hospitalization (28% vs. 26%, respectively)
      and at 6 months (17% vs. 16%). Angiography was performed in 67% vs. 75%; CPU
      patients less frequently underwent revascularization (53% vs. 76%; p=0.002). In
      hospital duration was similar in both groups (7.5 days vs. 5.7 days). CPU
      patients had a 22% reduction in overall hospitalization costs compared with
      conventional management (9,913 vs. 12,056 euros/patient; p=0.01). This gain was
      particularly relevant (29%) when patients with TIMI risk score < or =4 were
      considered (10,599 vs. 13,699 euros/patient; p=0.004). CONCLUSIONS: CPU care of
      NSTEACS is a safe and cost-effective alternative to conventional CCU management,
      particularly appealing with regard to patients presenting with intermediate TIMI
      risk score (< or =4) in whom CPU management could optimize the use of cath-lab
      facilities and dedicated cardiologists.

PMID- 15735562
TI  - Correlation between acoustic speech characteristics and non-speech motor
      performance in Parkinson Disease.
AB  - BACKGROUND: Research has found that non-speech motor deficits in Parkinson
      Disease (PD) can be consistently improved by levodopa medications and surgical
      treatment, but that speech and voice are only partially responsive to treatment.
      This has led to the assertion that speech is an axial (non-peripheral) feature of
      PD, along with other features that are only partially responsive to treatment
      (e.g., postural stability and gait). The current study tested this assertion via
      examination of the relationship between multiple measures of speech production
      and multiple measures of non-speech movement in individuals with PD.
      MATERIAL/METHODS: Nine individuals with idiopathic PD were studied, and all
      participants were taking levodopa-carbidopa medication. Motor performance was
      examined using the motor portion of the Unified Parkinson's Disease Rating Scale,
      and speech was examined via acoustic analysis of phonation, articulation, and
      prosody. RESULTS: Seven of sixteen speech acoustic measures (FoSD in vowels, F2
      slope for /u/ and /ae/, FoSD in reading, articulation rate in monologue, and
      percent pause in reading and monologue) were significantly correlated with non
      speech movements. Results suggested that speech measures are correlated with both
      axial motor symptoms (e.g., gait, facial expression, posture, postural stability)
      and non-axial motor symptoms (e.g., rest tremor, left and right bradykinesia,
      postural tremor). CONCLUSIONS: It has been hypothesized that axial symptoms of PD
      are more purely dopaminergic, and non-axial symptoms are related to non
      dopaminergic lesions. Therefore, the current results indicate that certain speech
      deficits in PD may result from dopaminergic lesions, while others appear to
      result from non-dopaminergic lesions.

PMID- 15735563
TI  - Infantile spasms: neurological and developmental follow-up--a comparison between
      two ethnic groups: Israeli Jews and Bedouin in the South of Israel.
AB  - BACKGROUND: The aim of this study was to examine all cases of infantile spasms
      (IS) diagnosed at the Soroka University Medical Center, Ben Gurion University,
      Israel during 1981--1997. MATERIAL/METHODS: 31 children, 17 (55%) males. 17 (55%)
      were Jews and 14 (45%) Bedouins. Four (13%) died. Data was gathered from hospital
      files, neuropediatric unit and Zusman Child Development Center. Demographic and
      ethnic data, characteristics of the disease type of seizures, EEG pattern imaging
      studies, type of treatment, psychomotor development, rehabilitation and
      educational services were analysed. RESULTS: Mean age at diagnosis 7.22 months.
      Etiology for one third was pre- or perinatal insult, one third postnatal and one
      third unknown. 26 (84%) were symptomatic and five (16%) cryptogenic. Significant
      statistical difference was found with more Bedouin children symptomatic with
      moderate or severe mental retardation, cerebral palsy with severe motor
      difficulties and recurrence of the disease. Statistically significant correlation
      existed between poor response to initial treatment and placement in special
      education, recurrence of disease and cerebral palsy with moderate or severe motor
      difficulties, the appearence of a different type of epilepsy during follow-up and
      placement in special education. 18 children (58%) received first treatment with
      ACTH, 10 (32%) children with IVIG (immunoglobolin iv), 3 (10%) with neither ACTH
      nor IVIG. Regarding therapy response we found no significant difference between
      Jews and Bedouins. CONCLUSIONS: No significant statistical difference was found
      between the two treatments concerning clinical course or developmental follow-up.
      Due to small numbers multi-center research is needed.

PMID- 15735564
TI  - Her-2/neu over-expression correlates with more advanced disease in Iranian
      colorectal cancer patients.
AB  - BACKGROUND: Her-2/neu protein is a member of the epidermal growth factor family
      of receptors which, upon activation, contributes positively to the growth and
      dissemination of neoplasia. Over-expression of this protein has been reported in
      different human tumors and shown to be a valuable prognostic factor especially in
      breast cancer. A limited number of studies have also shown positive correlation
      between Her-2/neu over-expression and advanced tumor progression in colorectal
      cancer. Here we studied the prevalence of Her-2/neu over-expression in Iranian
      colorectal cancer patients and assessed its correlation with the disease's
      progression. MATERIAL/METHODS: Fifty-five colorectal cancer patients in different
      stages of disease were studied. The pathology specimens were
      immunohistochemically stained using monoclonal antibody against Her-2/neu
      protein. Correlation of the degree of staining with clinicopathological
      parameters was investigated. RESULTS: It was shown that in an Iranian population
      of colorectal cancer patients, the Her-2/neu oncogene is over-expressed in a
      significant number of cases and positively correlates with tumor stage and grade,
      being more frequent in the advanced and less differentiated samples. CONCLUSIONS:
      These data can be applied in designating new chemotherapeutic regimens using
      drugs that block the function of Her-2/neu in colorectal cancer patients in Iran.

PMID- 15735565
TI  - Anatomical and surgical study of totally extraperitoneal laparoscopic
      hernioplasty.
AB  - BACKGROUND: Laparoscopic surgery provides direct access to the extraperitoneal
      inguinal space for a clear, amplified view of the anatomical structures. However,
      the variety of terms used to describe the fascial elements has partly prevented
      the promulgation of this approach. MATERIAL/METHODS: Two hundred patients
      received surgery for inguinal hernia at an outpatient surgery unit by means of
      totally extraperitoneal laparoscopy. Regional anatomical dissection was performed
      during the operation, which was filmed for later analysis. DISCUSSION: The
      totally extraperitoneal laparoscopic technique is described anatomically,
      including management of the internal spermatic fascia to create an opening for
      the use of fenestrated meshes. The technical maneuvers are discussed, with
      comparison of other possible methods of approach. CONCLUSIONS: From our
      experience we would recommend: 1) a consensus on terminology is necessary for
      dissemination of the TEP approach; 2) the ISF must be dissected to avoid ruptures
      of the sac and ensure parietalization; 3) the "sling of the TF" must be
      preserved, and 4) the TEP approach does not require dissection medial or inferior
      to the Cooper ligaments.

PMID- 15735566
TI  - Helicobacter pylori and nonsteroidal anti-inflammatory drugs in perforations and
      bleeding of peptic ulcers.
AB  - BACKGROUND: This study was designed to assess the relative contribution of H
      pylori (Hp) infection and NSAID in the pathogenesis of perforation and bleeding
      of peptic ulcer (PU). MATERIAL/METHODS: Total of 91 PU perforations and 135
      active bleeding were examined during last 5 years. At the same time, 1384 age-
      and gender-matched PU patients without such complications were examined.
      Furthermore, the effects of various concentrations of aspirin on the growth of Hp
      isolated from antral mucosa of these PU were examined in vitro. RESULTS: The
      average rates of Hp prevalence in PU patients with perforation or bleeding in
      NSAID intake were, respectively, only 50% and 62% as compared to 70.7 and 74% in
      PU patients non-using NSAID. The Hp prevalence in perforated and bleeding PU at
      all ages, particularly those at age of 60 years or higher, were significantly
      lower compared to that found below this age, while no such difference in Hp
      infection rate was seen in PU not using NSAID. In vitro studies on CagA and VacA
      positive Hp subjected to culture medium containing aspirin showed a dose
      dependent reduction in bacterial growth with complete bacteria killing occurring
      at 500 microg/ml of aspirin. CONCLUSIONS: The Hp prevalence, especially in older
      PU patients using NSAID, is significantly lower in perforated and bleeding PU
      compared to that in non-complicated PU, and this could be explained by direct
      suppression of Hp by NSAID used by these patients.

PMID- 15735567
TI  - Usefulness of ascitic fluid cholesterol as a marker for malignant ascites.
AB  - BACKGROUND: The differential diagnosis of ascites is a common clinical problem.
      However, the capability to distinguish malignant from non-malignant causes of
      ascites using available biochemical techniques would obviate many expensive and
      time-consuming diagnostic studies on patients presenting with ascites of unknown
      etiology. Therefore, this study was planned to evaluate the diagnostic efficacy
      of ascitic fluid cholesterol in comparison to the efficiency of ascitic/serum
      total protein, pH, glucose, total leukocyte count, and the serum/ascitic albumin
      gradient in differentiating "malignant" from non-malignant ascites.
      MATERIALS/METHODS: A total of 50 patients (25 with malignant ascites and 25 with
      non-malignant) were evaluated for total ascitic protein, ascites/serum (A/S)
      total protein ratio, serum ascites albumin gradient (SAAG), ascitic pH, serum &
      ascitic cholesterol with glucose. RESULTS: The mean ascitic cholesterol level was
      significantly higher in malignant ascites than in non-malignant ascites, with a
      cut off level of 70 mg/dl for ascitic fluid cholesterol; 22/25 (88%) patients
      with malignant ascites could be separated from the 25 patients with non-malignant
      ascites. The specificity (100%) and diagnostic efficiency (94%) of ascitic fluid
      cholesterol is better than the 84% specificity and 86% diagnostic efficiency of
      serum ascitic albumin gradient. CONCLUSIONS: Total Ascitic protein (70%), Ascitic
      serum protein ratio (74%), ascitic leukocyte count (54%), and malignant cytology
      (82%) yielded much lower diagnostic efficiency than ascitic fluid cholesterol
      (94%) or SAAG (86%) in the diagnosis of malignant ascites.

PMID- 15735568
TI  - Autologous gamete cryopreservation before hemopoietic stem cell transplantation.
AB  - BACKGROUND: Infertility after hemopoietic stem cell transplantation (HST) is a
      serious problem for young patients. Autologous gamete collection before HST may
      be a promising strategy to overcome infertility. MATERIAL/METHODS: From October
      1988 to December 2003, six male and nine female patients with hematological
      malignancies had autologous gametes collected before HST. The data on autologous
      gamete collection were analyzed. RESULTS: Sperm could be collected from three
      patients. However, in two of the three, the numbers and motility of the sperm
      were severely depleted because they received chemotherapy for one and 11 cycles,
      respectively. Normal sperm was only collected from one patient with
      myelodysplastic syndrome who had no history of receiving chemotherapy. One or
      more oocytes could be collected in five of nine female patients, although the
      five received multiple cycles of chemotherapy. The successful oocyte collection
      was associated with an ovulation stimulant. CONCLUSIONS: Autologous oocye
      collection before HST may be possible, even if patients receive multiple cycles
      of chemotherapy. In contrast, autologous sperm collection before HST may be
      difficult after patients receive chemotherapy. Successful pregnancy using
      autologous gametes after HST remains extremely difficult, especially in female
      patients; however, it is important to give information on infertility and
      autologous gamete collection to patients scheduled for HST.

PMID- 15735569
TI  - Modified Mid America Heart Institute Coronary Care Unit scoring system--a new
      comprehensive prognostic index for Coronary Care Unit patients.
AB  - BACKGROUND: Prediction of long-term outcomes for patients presenting with cardiac
      events is important, but few predictive instruments are available. We previously
      developed an innovative scoring system, the Mid America Heart Institute (MAHI)
      Coronary Care Unit (CCU) scoring system, for quantifying outcomes of patients
      admitted to the CCU, using clinical events rather than solely physiologic and
      laboratory variables. The objective of our study was to validate a refined
      version of this system (MAHI-2) and to explore its prognostic value, we have
      postulated that patients with high MAHI scores would have higher mortality and
      morbidity in 1-year follow-up. MATERIAL/METHODS: 154 patients admitted to the CCU
      were followed and assigned a MAHI score based on key clinical variables and
      events. The patients were followed for 1 year and outcomes were analyzed based on
      MAHI score quartiles. RESULTS: The mean MAHI-2 score was 14+/-8. Over one year,
      34 patients died, 13 suffered myocardial infarction, 12 had coronary artery
      bypass graft, 6 had percutaneous transluminal coronary angiography, 37 had a
      cardiovascular-related admission, and a total of 48 (31%) suffered >1 major
      adverse cardiac event (MACE - death/myocardial infarction/revascularization).
      MACE rates increased progressively by MAHI-2 score quartile (from 21% for those
      in the lowest quartile, to 42% in the highest quartile; p=0.22). The risk of
      death was more strongly correlated with MAHI-2 score, with patients in the
      highest quartile being at 6-fold greater risk for death in 1 year than those in
      the lowest quartile (p<0.0017). CONCLUSIONS: The MAHI-2 score appears to be a
      useful tool for predicting 1-year clinical outcomes based on in-hospital events.

PMID- 15735570
TI  - Bile leakage presenting as acute abdomen due to a stone created around a migrated
      surgical clip.
AB  - BACKGROUND: Surgical clips may migrate into the common bile duct after surgery
      for cholecystolithiasis leading to usually early or middle-term complications.
      CASE REPORT: A 31-year-old woman, 6 years after laparoscopic cholecystectomy,
      developed acute abdomen and choloperitoneum after rupture of a secondary bile
      duct and bile leakage. This complication was due to a solitary common bile duct
      stone. The stone was formed around a surgical clip that had migrated from the
      cystic duct remnant to the common bile duct. The patient underwent investigative
      laparotomy and, subsequently, an ERCP with stone extraction and clearance of the
      common bile duct. She was perfectly well at the follow-up after 14 months.
      CONCLUSIONS: Rupture of a bile duct and biliary peritonitis may be a delayed
      complication of laparoscopic cholecystectomy due to surgical clip migration and
      formation of a stone. Definitive treatment of the condition may be achieved
      through ERCP. Surgeons, gastroenterologists and radiologists should be aware of
      this late complication of laparoscopic cholecystectomy in cases of acute abdomen.

PMID- 15735571
TI  - Segregation of the marker chromosome der(20) in the sperm of a male with
      karyotype 46,XY[961/ 47,XY+mar[4].
AB  - BACKGROUND: The influence of the marker chromosome on reproductive failure is
      difficult to assess, especially in the case of low-rate mosaicism. The aim of our
      work was to examine the meiotic segregation of the marker chromosome der(20) in
      the sperm of a normal male whose wife had experienced three miscarriages, and
      therefore to determine whether there occurred a gametogenic tissue-specific
      mosaicism. MATERIAL/METHODS: The proband was a phenotypically normal 35-year-old
      man, referred for pre-conceptional counseling after his wife had experienced
      three miscarriages. Chromosome cytogenetic analysis was performed on peripheral
      blood lymphocytes using routine protocols. Sperm chromosome complements were
      obtained after penetration of zona-free hamster oocytes. Dual-color FISH analysis
      was performed using directly labeled probes identifying X, Y, 9 and 20
      chromosomes. RESULTS: A small marker chromosome der(20) was identified in 4% of
      the proband's lymphocytes and 8.25% of his sperm, which indicated mosaicism among
      the gametogenic cells, in which the proportion of cells containing the der(20)
      marker may reach a minimum of approx. 16%. CONCLUSIONS: In this case, we
      addressed a problem whether a revealed marker der(20) was the cause of
      reproductive failure or just a coincidental finding. In our view, each case of
      low-rate mosaicism of the marker chromosome should be individually assessed.

PMID- 15735572
TI  - Steroid sulfatase inhibitors as novel additions to the antipsoriatic
      armamentarium.
AB  - Psoriasis is a clinical conundrum that affects an estimated 1-3% of the world's
      population. The psoriatic disease process, characterized by a type 1 cytokine
      pattern, is supposed to be maintained by a continuing immune response in a
      "peripheral lymphoid tissue" that forms in lesional skin and is composed of T
      cells, dendritic cells, and vessels arranged like a T-dependent zone in lymph
      nodes. Dehydroepiandrosterone (DHEA), produced from dehydroepiandrosterone
      sulfate (DHEAS) through the enzymatic activity of DHEA-sulfatase, plays a pivotal
      role in the development of the type 1 immune response generated in peripheral
      lymphoid organs. Taken together, it could be reasoned that DHEA-sulfatase
      inhibitors may have utility in the treatment of psoriasis. Furthermore, the
      addition of DHEA-sulfatase inhibitors to calcipotriol, which encourages type 2
      immune response, may provide an additive or synergistic inhibition of the type 1
      immune response underlying psoriasis. It has been shown that topical application
      of cholesterol sulfate in the hairless mouse causes epidermal hyperkeratosis,
      which can be prevented by co-application of topical cholesterol. Therefore, as
      the inhibition of conversion of cholesterol sulfate to cholesterol can induce
      epidermal hyperkeratosis and may thus abbreviate the benefit obtained by
      inhibition of DHEAS to DHEA conversion, topical sulfatase inhibitors should
      preferably be co-applied with topical cholesterol, though it is also possible
      that the beneficial immunological effects of steroid sulfatase inhibitors
      outweigh their possible hyperkeratosis stimulation. Alternatively, the production
      of specific DHEA-sulfatase inhibitors can resolve the above concern. DHEA
      sulfatase inhibitors may prove invaluable in the treatment of psoriasis.

PMID- 15735573
TI  - A word on glutamate uptake by rat brain astroglia incubated in human
      cerebrospinal fluid.

PMID- 15735574
TI  - Molecular diagnosis of synovial sarcoma: RT-PCR detection of SYT-SSX1/2 fusion
      transcripts in paraffin-embedded tissue.
AB  - BACKGROUND: Synovial sarcomas comprise up to 10 percent of malignant soft tissue
      tumors, and most are characterized by the chromosomal translocation t(X;18) (pl
      1.2;q11.2), which results in the expression of SYT-SSX fusion transcripts. These
      tumors include two major histological subtypes, biphasic and monophasic.
      Diagnosing biphasic synovial sarcomas does not usually pose a problem, whereas
      the monophasic spindle-cell form can be difficult to distinguish from other
      spindle-cell neoplasms using histological and immunohistochemical profiles only.
      MATERIAL/METHODS: We investigated the presence of SYT-SSX1/2 chimeric RNA in
      tumors from 7 patients. We applied amplification of the specific fusion
      transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) in fresh,
      frozen tumors. We also developed a method useful for RT-PCR SYT-SSX fusion
      transcript detection in formalin-fixed, paraffin-embedded tissue. RESULTS: We
      found that both histological subtypes of synovial sarcoma were SYT-SSX positive.
      Moreover, we observed a correlation between histological subtype and type of SYT
      SSX fusion transcript. Biphasic synovial sarcoma expressed the SYT-SSX1 fusion
      transcript, whereas the monophasic subtype expressed the SYT-SSX2 fusion
      transcript. CONCLUSIONS: The detection of SYT-SSX1/2 fusion transcripts by RT-PCR
      is a valuable diagnostic marker of synovial sarcoma which can be used for the
      reclassification of cases whose diagnosis is difficult by routine methods.

PMID- 15735575
TI  - Variation in MRI/CT utilization among FAMILY physicians and general internists in
      a multi-specialty group practice.
AB  - BACKGROUND: The objective of this study was to examine variations in MRI/CT
      utilization between family physicians (FPs) and general internists (IMs) within a
      multi-specialty group practice. MATERIAL/METHODS: Using administrative data, we
      computed ordering rates of MRI/CT per 1,000 outpatient clinic visits and per
      1,000 unique patients and rate ratios (RR) to compare rates between 34 FPs and 24
      IMs practicing in 7 clinics located within 50 miles of the radiology facility. We
      also assessed intra-specialty variation. Sources and degree of variation were
      determined separately for FPs and IMs through multivariate linear regression
      modeling. RESULTS: The IMs ordered MRI/CTs at twice the rate of FPs (29.6 vs.
      14.8 per 1,000). Although the absolute ranges by specialty were statistically
      similar, the variance was significantly higher for IMs (86.1 vs. 52.3; p<0.0001).
      FPs' ordering rates ranged from 2.8 to 35.2 (SD=7.23), while IMs' ranged from
      16.0 to 47.9 (SD=9.27). Female physicians ordered the tests at a higher rate
      (RR=1.38; 95% CI=1.17-1.53). After controlling for physician gender, years of
      practice, and patient panel size, distances from their clinics to the radiology
      facility site and patient severity index were the only variables that were
      significantly associated with MRI/CT ordering among FPs, explaining 39% of the
      total variance. CONCLUSIONS: Although IMs ordered MRI/CTs at a higher rate, as
      were females from both specialties, there was a higher ratio between high and low
      FP utilizers. The variation in FPs can be partly explained by their clinic
      distance to the radiology facility site and their patient severity index.

PMID- 15735576
TI  - US, MRCP, CCT and ERCP: a comparative study in 131 patients with suspected
      biliary obstruction.
AB  - BACKGROUND: Recent years have witnessed a rapid and continuous evolution in the
      diagnosis of biliary obstructive disease. Traditional methodologies, such as US
      (ultrasonography), CT (computed tomography), ERCP (endoscopic retrograde
      cholangiopancreatography) and PTC (percutaneous transhepatic cholangiography),
      have been supplemented by MRCP (magnetic resonance cholagiopancreatography) and
      CCT (cholangio computed tomography) The purpose of our study was to compare the
      reliability of diagnostic US, MR and other imaging techniques in intrinsic
      biliary obstructive disease. MATERIAL/METHODS: Between June 1999 and July 2003 we
      conducted a prospective study on 131 patients--60 males and 71 females--ranging
      in age from 37 to 79 years, with clinical features of biliary obstructive
      disease. Imaging studies were done on each patient using several different
      techniques. The US, MRCP, CCT and ERCP results were read by radiologists blinded
      to other imaging findings. RESULTS: US is generally accurate in diagnostic
      imaging of obstructive biliary disease. MRCP and CCT are significantly more
      accurate only in completing the staging of malignant stenosis. CONCLUSIONS: If
      the suspicion posed by clinical and laboratory findings is not confirmed at US,
      the diagnosis must be achieved with the aid of MRCP or--where MRCP does not
      provide a diagnosis--CCT, so as to select candidates for therapeutic ERCP, PTC or
      surgery. If laboratory and clinical findings are supported by US, ERCP is
      required for therapeutic purposes, or--if necessary--surgery is performed.

PMID- 15735577
TI  - Do microbes have a causal role in type 1 diabetes?
AB  - Type 1 diabetes mellitus (T1DM) results from environmental factors acting on
      genetically susceptible individuals. Microbial infections and their immunological
      consequences are suspected to take part in the pathogenesis of T1DM. Congenital
      rubella infection has been strongly associated with increased disease
      susceptibility. In addition, infections with different strains of enteroviruses,
      human cytomegalovirus, and rotavirus have been suggested to be diabetogenic in
      susceptible individuals. A newly emerged hypothesis states that a bacterial
      toxin, bafilomycin A1 produced by Streptomyces spp, could be the cause of
      pancreatic beta-cell damage. In some instances, microbial infections may even
      protect the individual from T1DM. There are several proposed mechanisms of beta
      cell damage caused by microbes. T1DM can result from direct cytolysis of beta
      cells. Other suggested mechanisms are cross-reactivity between microbial proteins
      and self antigens (molecular mimicry), bystander activation of lymphocytes, and
      alterations in cytokine concentrations affecting T-helper cell balance in the
      vicinity of pancreatic beta-cells. Proving a causal role between microbial
      infections and T1DM appears difficult. Despite intensive research, a final
      conclusion concerning the causal role of microbes in the pathogenesis of T1DM has
      not been made.

PMID- 15735578
TI  - Insulin resistance and other metabolic aspects of the obstructive sleep apnea
      syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is usually associated with conditions
      known to increase insulin resistance and cardiovascular risk, such as
      hypertension, obesity, and diabetes. Thus, investigating whether obstructive
      sleep apnea itself is an independent risk factor for increased insulin resistance
      and whether continuous positive airway pressure treatment (CPAP) might improve
      insulin sensitivity brings up considerable methodological problems. Even if
      insulin sensitivity improves, it is hard to distinguish between an effect of CPAP
      treatment, e.g. in the reduction of nocturnal sympathetic activity caused by the
      sleep disturbance, and concomitant factors, such as weight loss. Two recent
      investigations were able to prove that OSAS is an independent risk factor for
      insulin resistance: one study in a statistical approach, the other by
      demonstrating a significant improvement of insulin sensitivity already two days
      after onset of CPAP therapy, thus clearly ruling out such confounding factors as
      changes in lifestyle or weight loss. However, it is still not clear if this
      improvement in insulin sensitivity is accompanied by an improvement in the
      usually elevated cardiovascular risk of patients with OSAS. Since a decrease in
      elevated markers of subclinical inflammation--nowadays regarded as the main
      culprit of cardiovascular complications and atherosclerosis--such as Interleukin
      6 and C-reactive protein has been reported during CPAP therapy, and since an
      improvement in left ventricular function and a decrease in blood pressure were
      also reported under CPAP treatment, there are several good reasons to assume an
      improvement in metabolical function in OSAS patients due to CPAP treatment.

PMID- 15735580
TI  - Contemporary treatment of ductal carcinoma in situ of the breast.
AB  - The main controversies surrounding the management of DCIS evolve around the need
      for adjuvant radiotherapy (RT) after adequate local excision (LE) of localized
      lesions and the role of adjuvant endocrine therapy. All randomized controlled
      trials (RCTs) examining the role of adjuvant RT and tamoxifen after LE were
      reviewed. The review also included important retrospective studies examining the
      treatment options for DCIS. All three RCTs demonstrated that adjuvant RT
      significantly reduced the incidence of ipsilateral breast tumour recurrence
      (IBTR) after 'adequate' LE of localised DCIS. Retrospective studies showed that
      the most significant effect for RT in DCIS was in women with high grade disease,
      with necrosis, large lesions and/or close margins. Total mastectomy is associated
      with the lowest rates of IBTR, but there is no evidence that it is superior to LE
      in terms of overall survival. Tamoxifen may be used in very selected patients
      with hormone sensitive (ER+) disease when the benefits outweigh the potential
      risks. Total mastectomy remains the treatment of choice for multicenteric and/or
      extensive disease. RT significantly reduces the risk of recurrence after adequate
      LE of localized DCIS. Radiation may be safely omitted after breast-conserving
      surgery (BCS) in postmenopausal women with low risk DCIS (USC/VNPI score =4-5).
      Tamoxifen can be considered in high-risk young women (USC/VNPI score =9-12)
      treated by BCS for ER+ DCIS as long as the potential benefits and adverse effects
      are explained to the patient.

PMID- 15735579
TI  - Septic shock; current pathogenetic concepts from a clinical perspective.
AB  - Sepsis is an infection-induced syndrome characterized by a generalized
      inflammatory state and represents a frequent complication in the surgical
      patient. The normal reaction to infection involves a series of complex
      immunologic processes. A potent, complex immunologic cascade ensures a prompt
      protective response to microbial invasion in humans. Although activation of the
      immune system during microbial invasion is generally protective, septic shock
      develops in a number of patients as a consequence of excessive or poorly
      regulated immune response to the offending organism (Gram-negative or Gram
      positive bacteria, fungi, viruses, or microbial toxins). This unbalanced reaction
      may harm the host through a maladaptive release of endogenously generated
      inflammatory compounds. Many mechanisms are involved in the pathogenesis of
      septic shock, including the release of cytokines, the activation of neutrophils,
      monocytes, and microvascular endothelial cells, as well as the activation of
      neuroendocrine reflexes and plasma protein cascade systems, such as the
      complement system, the intrinsic (contact system) and extrinsic pathways of
      coagulation, and the fibrinolytic system. In critically ill patients, the
      gastrointestinal tract plays a central role in the pathogenesis of septic shock.
      The potential for complementary and synergistic interaction of the different
      components in this cascade highlights the difficulty encountered in trying to
      identify a single means of altering the progression of sepsis and septic shock to
      multiple organ dysfunction syndrome (MODS) and multiple organ failure (MOF).

PMID- 15735581
TI  - Stage-specifically expressed schistosome proteins as potential chemotherapeutic
      targets.
AB  - Digenetic trematodes have evolved behavioral adaptations to their complex life
      cycles. They have their own strategies to find hosts, locate sites of infection
      within final and intermediate hosts, escape immune responses, etc. Many of these
      strategies are highly complex, but they are sometimes quite subtle. While the
      mechanisms or processes involved in a few parasites are understood, most are not.
      Schistosoma mansoni parasites inhabit three distinct environments: water,
      intermediate molluscan hosts, and a definitive vertebrate host. Although targeted
      chemotherapy and other public health measures are employed to control
      schistosomiasis and its spread, there is a need for the development of vaccine
      and new anti-schistosome drugs. Determining how schistosomes interact with
      different environments may be one mechanism by which suitable vaccine or
      chemotherapeutic drugs could be developed. Genes expressed in a stage-specific
      manner may help us to understand the molecular events controlling the complex
      life cycle of schistosomes. Various proteins are expressed during the life cycle
      of schistosomes which are essential for its miracidial infection of molluscan
      hosts, cercarial penetration of vertebrate skin, evasion of the immune responses
      of both hosts, and other biological activities needed by schistosomes to complete
      their complex life cycle. Identifying these stage-specific proteins may uncover
      hidden aspects of parasite biology and provide useful leads for the development
      of novel intervention strategies.

PMID- 15735583
TI  - Neonatal Health Psychology [NNHP]: theories and practice.
AB  - By 1994, Health Psychology had been established as a discipline, and defined by
      Marie Johnston as the scientific study of the psychological processes and
      behaviour in health, illness and health care. Health Psychology, so far, has
      mainly related to the adult population, although increasing attention is now
      being paid to both pediatric and broadly-based child health psychology. It is
      noteworthy that attention devoted to pediatric and child health psychology has
      increased dramatically, but the great majority of published work refers to the
      child and not to the preterm neonate; yet being preterm means being born early,
      and sometimes too small, and is a stressful life event. In the field of Medicine,
      Neonatology has appeared as a sub-discipline, and both investigates and cares for
      at-risk babies, including risk for developmental disabilities. The time is
      consequently opportune for psychology to make an effective contribution to both
      the theory and care of the preterm neonate, viewed as a unique, emergent,
      coactional and hierarchical human being. The formal framework for this is
      Neonatal Health Psychology (NNHP), which is defined in the article as 'the
      scientific study of biopsychosocial and behavioural processes in health, illness,
      and health care of the preterm (and fullterm) neonate during his/her first 28
      days of life, and the relationship of such processes with later outcome.' Early
      work in this category has shown that NNHP has profound interdisciplinary
      connotations, not least because of the diverse ways in which information has to
      be derived from the non-verbal neonates. The pathways and scope of NNHP are
      identified, and many examples of work with preterm neonates are summarised in the
      article. In making the case for the professional formalization of NNHP,
      descriptions are given of Neonatal Assessments and very-early interventions; the
      interdisciplinary character of much of the early work is shown to have been
      essential. Indication of theoretical frameworks for NNHP is given.

PMID- 15735584
TI  - Detection and prevention of premature labour.
AB  - Preterm birth is a major public health problem, affecting up to 10% of
      pregnancies. The cause of premature labour in humans is not known, although some
      risk factors have been identified. Currently it is not possible to predict which
      women will go into labour prematurely or deliver preterm. New possible methods
      for the detection of premature labour are the measurement of biochemical markers
      in cervical or vaginal secretions, the measurement of collagen in cervical tissue
      and the recording of electrical properties of contractions of the uterus. Agents
      used to prevent premature labour include beta-agonist drugs, magnesium sulphate,
      calcium channel blockers, nitric oxide donors and prostaglandin synthesis
      inhibitors. A new approach is the use of oxytocin antagonists. Premature labour
      is still not completely understood, but some advances are being made, arising
      from basic research.

PMID- 15735585
TI  - The epidemiology of preterm birth.
AB  - Preterm birth is a major clinical problem, accounting for 47% of all neonatal
      deaths. The preterm delivery rate in UK is approximately 7%, and rates of preterm
      birth are steadily increasing. The diagnosis of preterm labour is difficult and
      most interventions to halt labour are unsuccessful. Despite this, the lack of
      good data hinders high quality research. The West Midlands has the highest
      perinatal mortality in the UK and a Perinatal Institute was set up in 2000 to
      address this, and aid improvements in care. Survival rates amongst preterm
      infants have changed dramatically over the last decade, with 88% survival for
      2728 weeks, and 21% for > or =24 weeks (depending on birth weight). Risk factors
      include lower social class, less education, single marital status, low income,
      younger maternal age, low body weight, ethnicity, smoking, poor housing along
      with medical factors such as induction, premature rupture of membranes,
      infection, multiple pregnancy intrauterine death, fetal and uterine abnormalities
      and chorioamnionitis. Data from further detailed, robust studies are required to
      facilitate a comprehensive understanding of risk factors and their relationship
      with each other. Only then will it be possible to influence the adverse outcomes
      described.

PMID- 15735586
TI  - Pain and compassion in the neonatal unit -- a neonatologist's view.
AB  - Research has shown that even extremely premature babies are sufficiently
      developed, anatomically and physiologically, to be capable of experiencing and
      responding to pain. All newborn infants and especially those who require
      intensive care in the first days of life are exposed to some painful procedures.
      Part of the neonatologist's role is the detection and management of pain in these
      infants. Difficult challenges come with this role. All medications carry known or
      potential adverse effects and limited research has been done in this vulnerable
      population. The benefits and risks of all available pain-relieving measures
      should be balanced when planning management. Compassion is no excuse for a high
      incidence of undesirable or dangerous side effects. We must proceed with great
      care.

PMID- 15735587
TI  - Preterm neonatal neurological examination.
AB  - This chapter covers the purposes for which a neurological examination of a
      neonate may be performed. A brief description is given, of assessments currently
      in use. More extensive information is provided on the elements of the
      Neurobehavioral Assessment of the Preterm Infant (NAPI), an assessment which has
      been used extensively by this author and others (see references at www
      med.stanford.edu/school/pediatrics/NAPI/index). Medical and environmental factors
      that impact on the neurobehavioral performance of an infant are outlined. Two
      detailed case studies give insight to the complexity of the initial hospital stay
      of extremely low birth weight infants of short gestational age. The results of
      NAPIs for each of these cases are explained and the relation to long term outcome
      at 18 months is presented.

PMID- 15735588
TI  - TAC-TIC therapy with premature infants: a series of investigative studies.
AB  - This article provides a synopsis of a series of studies exploring the effects of
      TAC-TIC (Touching And Caressing-Tender In Caring) therapy with premature infants.
      Study 1 looked at the short and long-term effects and found enhanced mental
      development in the stroked infants at 15 months. In study 2 the physiological
      effects of an abbreviated version of TAC-TIC with high-risk ventilated infants
      were examined and it was concluded that TAC-TIC exerted no harm to these
      vulnerable infants. The behavioural reactions of a sample of premature and low
      birthweight infants to TAC-TIC and parental responses to administering it were
      explored in study 3. The infants were found to respond predominantly with arm and
      leg movements to TAC-TIC while fathers and mothers reported enjoying performing
      TAC-TIC and elicited a similar pattern and frequency of behavioural reactions. In
      study 4 the question of whether TAC-TIC benefits preterm infant learning and/or
      sucking behaviour was investigated. The conclusion reached was that TAC-TIC may
      potentially benefit cognitive performance within the neonatal period and that
      this may be an early indicator of long-term cognitive gains reported by previous
      studies. Using a matched subjects design, study 5 explored the impact of TAC-TIC
      upon the digestive system by analysing gastric aspirates before and after TAC-TIC
      and a control period of time. It was concluded that TAC-TIC appeared to induce a
      more suitable stomach environment for digestion.

PMID- 15735589
TI  - Continuing psychological care.
AB  - This article draws together thoughts derived from an experienced clinical
      psychologist's practice, with parents of ill and premature infants in the context
      of a psychological service for children and parents in a paediatric and maternity
      teaching hospital. Parents were those referred by attendant neonatologists in
      intensive neonatal care who observed acute distress. Referral was usually some
      weeks after birth and help continued until after discharge, in some instances
      after the death of the infant. The particular approach adopted was that of
      offering parents a therapeutic contact which, allowed them talk over these
      thoughts and feelings for which they had little other skilled listening
      environment. Parents chose the opportunity of a safe, calm and confidential
      contact to explore deep feelings and draw on their own strengths and an
      understanding of their own vulnerabilities. The novel insights derived and the
      clinical material presented were used to develop an understanding of the issues a
      support service should address. Key aims are described and should be incorporated
      to restore and enhance personal strengths and the mother child relationship hence
      contributing to positive outcome in infant development. Reference is made to the
      importance of understanding how women achieve soothed states and restoration of
      empowerment when birth presents extra challenge.

PMID- 15735590
TI  - Family centred care for the neonate -- the view from Wolverhampton.
AB  - The increased technology of neonatal intensive care has meant that babies born at
      increasingly lower gestational age are surviving to be discharged home. A family
      centred approach in neonatal care supports the move toward patient or parent
      empowerment, which is vital, if babies are to be fully integrated into the family
      unit. Nurses are essential to the success of this process as they have the most
      direct and prolonged contact with both family and their baby. Critical care areas
      such as Neonatal Units (NNU) can be adjusted to support a more family focused
      philosophy. In Wolverhampton Orems 'Self-Care Model' of self care has been
      adapted to the family as the self care unit and simple adjustments to the area
      such as Quiet Times supports families feeling of well being and control.

PMID- 15735591
TI  - Perceived Parenting Self-Efficacy (PMP S-E) of mothers who are breastfeeding
      hospitalised preterm neonates.
AB  - Breastfeeding is a complex task for many mothers but may be particularly
      difficult when coping with the birth of a preterm. In the following article the
      task of breastfeeding a preterm neonate is identified as one facet of the
      parenting process and the many problems encountered when breastfeeding are
      highlighted. Research is presented which investigates whether breastfeeding a
      preterm neonate mediates mothers' Perceived Parenting Self-Efficacy (PMP S-E)
      whilst in hospital. The findings from this study suggest that not only do mothers
      who are breastfeeding their preterm neonate have a lower self-efficacy than non
      breastfeeding mothers, but they also require further support in all aspects of
      parenting. The authors discuss these results in terms of self-efficacy theory and
      suggest that they may have implications for Neonatal Health Psychologists
      practice particularly with regard to the facilitation of breastfeeding within the
      neonatal unit.

PMID- 15735592
TI  - A role for counselling psychologists within the Neonatal Intensive Care Unit.
AB  - Counselling psychology appears to be neglecting the importance and merits of
      working with the client population associated with the preterm neonate within the
      Neonatal Intensive Care Unit (NICU). Throughout, the benefits of such a move are
      highlighted with particular emphasis on how counselling psychologists are
      uniquely qualified for this role. Specialist knowledge required to provide
      clients with the greatest therapeutic gains illustrates the pertinent issues,
      with proposals for clinical practice put forward. NHS Trusts nationwide are
      encouraged to recruit this ready-made professional into the Department for the
      psychological health of parents and caregivers engaged in caring for the preterm
      neonate.

PMID- 15735593
TI  - The mother-baby relationship in the event of extreme prematurity: intervention
      possibilities within a multidisciplinary team.
AB  - The purpose of this study is to consider the intervention possibilities within a
      multidisciplinary medical team during the hospitalization of extremely preterm
      infants. In this work, the interventions were carried out with the objective of
      establishing communication among the various parties involved, mother, infant and
      multidisciplinary team, by approaching and trying to understand the mother in the
      diverse moments of hospitalization of preterm infants.

PMID- 15735594
TI  - Prematurity and adult minor illness.
AB  - The long term impact of being born premature has received limited scientific
      investigation. Studies that have been carried out, focus on outcomes in
      childhood, with very few considering the impact on adult physical health. Three
      case studies are presented here, investigating differences in adult minor illness
      and psychological variables between adult participants born preterm, fullterm but
      small and fullterm with normal birthweight. This is a retrospective design using
      questionnaires and checklist to gather relevant information. Minor illness
      symptoms, daily hassles, anxiety, depression and general self-efficacy were
      measured. The participant born preterm scored higher on all measures. Data were
      applied to the Equilibrium Model for Minor Illness. Being born early appears to
      have a greater impact on later adult outcomes measured than being born fullterm
      but small or fullterm but of normal weight. In this article the authors reflect
      upon possible explanations for the different outcomes of each of the participants
      within the foetal origins of disease theory.

PMID- 15735595
TI  - Life after the NNU: the long term effects on mothers' lives, managing a child at
      home with broncho-pulmonary dysplasia and on home oxygen.
AB  - This study investigated the long-term influences on mothers' lives having managed
      an infant with bronchopulmonary dysplasia (BPD), on home oxygen. 16 mothers UK
      wide, whose children had been at home for over a year, formed this project, and
      completed a semi-structured questionnaire. All mothers displayed a high standard
      of literacy and were English/British by their own description with no indication
      of cross cultural or ethnic differences. Mothers, giving up jobs and careers to
      remain home, were the primary carers for their child, and experienced long term
      emotional distress, suffered from lowered self-esteem over many years, self-blame
      in some cases and grieved over many aspects of pregnancy, birth, babyhood and
      early childhood. The fear of infection led to these mothers keeping themselves
      and their children isolated, compounded for half the mothers who faced negative
      reactions from the community when they did go out with their child.

PMID- 15735596
TI  - Born too soon.
AB  - In this Letter, the author walks through 'Memory Lane'. She reflects upon the
      birth, growth and developmental trajectory of her third child who was born too
      soon, in a major Hospital in London. Her aim is to share her knowledge and
      experiences with other parents and professionals. The author acknowledges the
      feelings which is so common amongst mothers of preterm babies i.e. that the baby
      does not belong to them. Moreover, she reflects upon her participation in caring
      for her daughter, how overwhelming it all was and her joy when her child left
      hospital and is a healthy teenager.

PMID- 15735597
TI  - Reflections on neonatal intensive care unit.
AB  - This article reflects on twelve years spent on a regional neonatal intensive care
      unit (NICU). The trials and tribulations experienced by parents and staff alike
      are described together with some of the initiatives developed to mitigate the
      effects of these. High standards of medical and nursing care, environmental
      conditions, good communications and a multi-disciplinary approach are all
      identified as crucial in giving holistic care to the neonate. Finally, the
      involvement of the professional team is recognised as transient but key in
      developing in the parents both competence and confidence in their roles for the
      future.

PMID- 15735598
TI  - The impact of different types of bath in the behaviour and physiology of 'rooming
      in' newborn babies.
AB  - The new scientific knowledge about the behaviour of the newborn and their
      interactions as a developing factor, as well as the new neurosciences findings
      about the initial brain formation, gave us several elements for a new vision and
      reflection about the perinatal routines in hospitals. This study raises questions
      about the first experiences of the rooming in newborns during the specific act of
      bath, as the only determining factor in altering both behaviour and physiology.
      Through the monitoring of the heart rate frequency and observing the changes in
      the states of consciousness level, this article shows how the type of bath that
      the newborn is subjected to influences his/her organisation. The study showed
      significant results in the parameters observed during the electric shower bath,
      leading to unbalance of the subsystems where the individuals organise themselves;
      such findings made us classify this procedure as very stressing to the baby. To
      the contrary the bath in the "Tummy Tub" presented insignificant changes, showing
      a relaxed baby with normal bath behaviours and physiological status; thus this
      procedure appears to contribute to an energetic and interactive balance of the
      baby's various systems. The aggressive approach (electric shower) does not allow
      the newborn auto-regulation to occur and to get proper stimulation and learn
      basic interactive responses which would facilitate his /her healthy early infancy
      development.

PMID- 15735599
TI  - Maternal-fetal attachment: searching for a new definition.
AB  - Maternal-fetal attachment is the purest source of the powerful attachment
      relationship, the gradual internalisation of the life within unspoilt by the
      realities and complexities of early parenting. This qualitative study searches
      for a definition of attachment utilising a phenomenological framework. An
      opportunity sample of 10 women in the final trimester of pregnancy was
      interviewed. Interviews were transcribed and analysed using Glaser & Strauss's
      (1967) constant comparative methodology. Thirteen key themes were identified, of
      these 4 were specific to parenting experience. A novel finding contrary to
      earlier studies was that women reported their overwhelming emotion was not love
      but an innate desire to protect. Protection, the developmental nature of
      attachment and importance of the emotional and physical support of a partner or
      parent form the kernel of an evolving paradigm.

PMID- 15735600
TI  - Grasping and fingering (active or haptic touch) in healthy newborns.
AB  - The traditional view that the activity of the baby's hands are triggered by a
      stimulus in an automatic, compulsory, stereotyped way and persisting view that
      fingering does not occur prior to 4 months of age, have led perception
      researchers to the assumption that the processing, encoding, and retainment of
      sensory information could not take place through the manual mode. This study aims
      to investigate whether fingering and different types of grasping occur before 3
      months of age and can be modulated by surface texture of three objects. Using
      naturalistic observations, this small sample developmental study applied the AB
      experimental design to achieve aims above. Babies were video taped every week for
      12 weeks. Three special manual stimuli were developed for this study. Focal
      sampling method with either zero-sampling or instantaneous sampling recording
      rules were used to analyse data with the Observer Video Pro. Each session
      comprising baseline and 3 experimental conditions lasted for four minutes.
      Fingering or 'proto fingering' as it is suggested in this article emerges as
      early as the first week of postnatal life; texture of a handled object modulates
      both 'proto-palm' and hand-grasp behaviour of healthy newborns. Results suggest
      that texture also modulates 'proto-fingering' and challenge persisting current
      assumption that fingering does not occur before four months of age, and further
      validates the phrase 'neo-haptic' touch to describe hands-on exploration of the
      newborn. The author suggests that some 'mental representation' of the stimulus is
      present during 'neo-haptic' recognition of the objects which is in accordance to
      a constructivist approach to (touch) perception.

PMID- 15735601
TI  - Direct action of platelet activating factor (PAF) induces eosinophil accumulation
      and enhances expression of PAF receptors in conjunctivitis.
AB  - PURPOSE: The goal of the present study was to investigate the role of platelet
      activating factor (PAF) and PAF receptor (PAF-R) in the recruitment of
      eosinophils into the conjunctiva in the course of PAF induced conjunctivitis.
      Eosinophils are important players in the immediate hypersensitivity reactions and
      in allergic conjunctivitis. PAF-R is expressed in many ocular tissues including
      conjunctival cells. Although it is known that PAF is one of the most potent
      chemotactic agents for the recruitment of eosinophils, factors responsible for it
      in conjunctivitis are not clear. Colocalization analysis has been employed to
      quantify the degree of colocalization of major basic protein (MBP) and PAF-R
      antigens in the course of PAF induced conjunctivitis. METHODS: A 1% solution of
      PAF was applied in eye drops to male Brown Norway rats. Eyes were harvested with
      intact conjunctivas at different time points and examined using histology,
      immunohistochemistry, confocal immunofluorescence microscopy, and reverse
      transcription-polymerase chain reaction. PAF-R and MBP (a marker of eosinophils)
      antibodies have been used for immunohistochemical studies. Quantitative analysis
      of the colocalization of PAF-R and major basic protein (MBP) antigens was
      performed. RESULTS: Instillation of PAF caused a time dependent recruitment of
      eosinophils. Eosinophils revealed PAF-R in the intact state. An influx of
      eosinophils into the conjunctiva was caused by the interaction of PAF with PAF-R
      and, possibly, with MBP antigen. PAF appeared to enhance the expression of PAF-R
      by eosinophils and to act toward the PAF-R directly, without chemokine mediation.
      CONCLUSIONS: Quantitative colocalization analysis helped to determine that the
      recruitment of eosinophils in PAF induced conjunctivitis is accomplished via
      direct action of PAF toward the PAF-R. It also ensured an objective evaluation of
      the changes of the degree of colocalization of MBP and PAF-R antigens and the
      degree of PAF-R expression in dynamics, the findings not otherwise obtainable
      using qualitative approaches alone.

PMID- 15735602
TI  - Nanoparticles for gene delivery to retinal pigment epithelial cells.
AB  - PURPOSE: To evaluate the safety and potential use of poly(lactic) acid (PLA) and
      poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) as vectors for gene
      transfer to RPE cells. METHODS: Experiments were conducted with primary bovine
      RPE cells and with the ARPE-19 human RPE cell line. Rhodamine loaded NPs were
      used to study factors influencing the internalization process by the various RPE
      cells: concentrations of NPs, duration of contact time, stage of cell culture and
      ambient temperature. The extent of NPs internalization was evaluated by
      fluorescence and phase microscopy. Potential NP toxicity was measured by the
      trypan blue exclusion dye test and the MTT method. Green fluorescent protein
      (GFP) plasmid or red nuclear fluorescent protein (RNFP) plasmid were sequestered
      in NPs. The ability ot these "loaded" NPs to generate gene transfection and
      protein expression in RPE cells was assessed both in vivo and in vitro by
      fluorescence and confocal microscopy. RESULTS: The extent of NP internalization
      in cultured cells increases with their concentration reaching a plateau at 1
      mg/ml and a contact time of up to 6 h. Temperature and culture stage did not
      influence the in vitro internalization process. No toxic effects on RPE cells
      could be detected when these were incubated with up to 4 mg/ml of NPs. In human
      and bovine RPE cells incubated with GFP loaded NPs, cytoplasmic green
      fluorescence was observed in 14+/-1.65% of the cultured cells. Incubation with
      RNFP loaded NPs yielded a nuclear red fluorescence in 18.9+/-1.6% of the cells.
      These percentage levels of expression initially detected after 48 h of incubation
      remained unchanged during the following 8 additional days in culture. No
      significant differences in the extent of cytoplasm or nuclear fluorescence
      expression were observed between bovine or human RPE cultured cells. In vivo, a
      preferential RNFP expression within the RPE cell layer was detected after intra
      vitreous injection of RNFP plasmid loaded NPs. CONCLUSIONS: The ability of PLGA
      NPs to sequester plasmids, their nontoxic characteristics, and rapid
      internalization enables gene transfer and expression in RPE cells. These findings
      may be of potential use when designing future gene therapy strategies for ocular
      diseases of the posterior segment.

PMID- 15735603
TI  - Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal
      epithelial cells.
AB  - PURPOSE: Pinin (Pnn/DRS/memA) plays an important role in regulating cell-cell
      adhesion of corneal epithelial cells. In the nucleus, Pnn interacts with both
      transcriptional repressor and pre-mRNA processing machinery. Here we investigated
      the consequences of "knocking down" Pnn expression with short hairpin RNAi
      (shRNAi) on the corneal epithelial cell phenotype. METHODS: Cultured human
      corneal epithelial (HCE-T) cells were cotransfected with a shRNAi-expressing
      construct containing an inverted repeat of a Pnn specific 21 nucleotide sequence
      (Pnn shRNAi) and a GFP vector as a marker of transfected cells. After 24-48 h,
      cells were fixed and immunostained with antibodies against Pnn, keratin,
      desmoplakin, desmoglein, E-cadherin, ZO-1, SR-proteins, and SRm300. To
      demonstrate specificity of the Pnn knock down, a rescue vector was designed by
      incorporating three conservative nucleotide substitutions within the Pnn-shRNAi
      targeting sequences of the full length Pnn-GFP construct, thus generating a Pnn
      construct to produce mRNA that Pnn shRNAi could not target (Pnn-CS3-GFP).
      RESULTS: HCE-T cells were cotransfected with Pnn shRNAi and GFP vectors and after
      24 and 48 h exhibited significantly reduced immunostaining for Pnn. Western blot
      analyses of Pnn and E-cadherin protein expression in cells transfected with Pnn
      shRNAi and GFP vectors revealed marked reduction in levels of both proteins
      compared to those observed in cells transfected with GFP alone. The cells
      receiving Pnn-shRNAi appeared to be less adherent to neighboring nontransfected
      cells, often exhibited altered cell shape, downregulated cell adhesion and cell
      junction molecules, and escaped from the epithelium. The Pnn shRNAi transfected
      cells exhibited fewer keratin filaments anchored to desmosomes and a concurrent
      increase in the perinuclear bundling of filaments. SR proteins and SRm300 showed
      an altered distribution in the Pnn knock down cells. Cotransfection of Pnn-CS3
      GFP with Pnn shRNAi demonstrated that the conservatively mutated Pnn could
      maintain cell-cell adhesion. CONCLUSIONS: Our results indicate that knocking down
      Pnn expression leads to a loss of epithelial cell-cell adhesion, changes in cell
      shape, and movement of Pnn shRNAi transfected cells out of the epithelium. We
      suggest that Pnn plays an integral role in the establishment and maintenance of
      epithelial cell-cell adhesion via its activity within nuclear multi-protein
      complexes.

PMID- 15735604
TI  - Autosomal dominant cone dystrophy caused by a novel mutation in the GCAP1 gene
      (GUCA1A).
AB  - PURPOSE: To describe the clinical features and genetic analysis of a family with
      an autosomal dominant cone dystrophy (adCD). METHODS: Selected members of a
      family with an autosomal dominant cone dystrophy underwent ophthalmic evaluation.
      Blood samples were obtained, genomic DNA was isolated, and genomic fragments were
      amplified by PCR. Linkage to locus D6S1017 was established. DHPLC mutational
      analysis and direct sequencing were used to identify a mutation in GUCA1A, the
      gene encoding the guanylate cyclase activating protein 1 (GCAP1). RESULTS: Of 24
      individuals who are at risk of the disease in a five generation family, 11
      members were affected. Clinical presentations included photophobia, color vision
      defects, central acuity loss, and legal blindness with advanced age. The disease
      phenotype was observed in the second and third decades of life and segregated in
      an autosomal dominant fashion. An electroretinogram performed on one proband
      revealed profoundly subnormal and prolonged photopic and flicker responses, but
      preserved scotopic ERGs, consistent with a cone dystrophy. Mutational analysis
      and direct sequencing revealed a C451T transition in GUCA1A, corresponding to a
      novel L151F mutation in GCAP1. Like the E155G mutation, this mutation occurs in
      the EF4 hand domain, a region of GCAP1 critical in conferring calcium sensitivity
      to the protein. The leucine at this position is highly conserved among vertebrate
      guanylate cyclase activating proteins. CONCLUSIONS: A novel L151F missense
      mutation in the EF4 high affinity Ca2+ binding site of GCAP1 is linked to adCD in
      a large pedigree. The cone dystrophy in this family shares clinical and
      electrophysiologic characteristics with other previously described adCD caused by
      mutations in GUCA1A.

PMID- 15735605
TI  - American Society for Clinical Pharmacology and Therapeutics position statement on
      dietary supplement safety and regulation.

PMID- 15735606
TI  - Pharmacogenetics and response to beta-adrenergic receptor antagonists in heart
      failure.

PMID- 15735607
TI  - beta-Adrenergic receptor polymorphisms and responses during titration of
      metoprolol controlled release/extended release in heart failure.
AB  - OBJECTIVE: beta-Blockers require careful initiation and titration when used in
      patients with heart failure. Some patients tolerate beta-blocker therapy
      initiation without difficulty, whereas in other patients this period presents
      clinical challenges. We tested the hypothesis that polymorphisms at codons 389
      (Arg389Gly) and 49 (Ser49Gly) of the beta(1)-adrenergic receptor would be
      associated with differences in initial tolerability of beta-blocker therapy in
      patients with heart failure. We also tested whether polymorphisms in the beta(2)
      adrenergic receptor, G-protein alpha s subunit (G(s)alpha), and cytochrome P450
      (CYP) 2D6 genes or S-metoprolol plasma concentrations were associated with beta
      blocker tolerability. METHODS: Sixty-one beta-blocker-naive patients with
      systolic heart failure were prospectively enrolled. Patients began taking 12.5 to
      25 mg metoprolol controlled release/extended release with titration every 2 weeks
      (as tolerated) to 200 mg/d or the maximum tolerated dose over a period of 8 to 10
      weeks. Decompensation was the composite of death, heart failure hospitalization,
      increase in other heart failure medications, or need to discontinue metoprolol.
      End points were assessed during the titration period. RESULTS: The overall rate
      of decompensation was not different between the codon 49 or 389 genotypes.
      However, a significantly greater percentage of patients with the Gly389 variant
      required increases in heart failure medications as compared with Arg389
      homozygotes (48% versus 14%, respectively; P = .006). Similarly, patients with
      the Ser49 homozygous genotype were significantly more likely to require increases
      in concomitant heart failure therapy as compared with Gly49 carriers (41% versus
      11%, respectively; P = .03). Neither CYP2D6 genotypes nor metoprolol
      pharmacokinetics differed between patients with and those without a
      decompensation event. There was no association between the beta(2)-adrenergic
      receptor or G(s)alpha polymorphisms with decompensated heart failure.
      CONCLUSIONS: Patients with the Gly389 variant and Ser49Ser genotype were
      significantly more likely to require increases in heart failure medications
      during beta-blocker titration and thus may require more frequent follow-up during
      titration.

PMID- 15735608
TI  - Polymorphism screening in the cardiac K+ channel gene KCNA5.
AB  - BACKGROUND: Common deoxyribonucleic acid polymorphisms that modulate normal
      cardiac electrophysiologic characteristics have previously been identified in
      long QT syndrome disease genes. In this study we screened an additional gene
      encoding the cardiac potassium channel KCNA5 (underlying I(Kur)) in 3 ethnic
      groups and evaluated the functional consequences of the variants identified.
      METHODS: The coding region was screened by single-stranded conformational
      polymorphism analysis and direct sequencing, and nonsynonymous variants were
      studied by patch-clamping transfected Chinese hamster ovary cells. Results Five
      synonymous and 6 nonsynonymous polymorphisms were found in KCNA5. None of these
      polymorphisms was present in greater than 7% of alleles screened or in all 3
      ethnic groups. Expression of the nonsynonymous KCNA5 variants revealed normal
      gating. However, 2 variants (P532L and R578K, both in the C-terminus) were
      resistant to block by the prototypical inhibitor quinidine; the concentration
      required to block I(Kur) by 50% (IC(50)) was 8.4 micromol/L for wild type versus
      54 micromol/L for R578K and 133 micromol/L for P532L (both P < .0001, versus wild
      type). CONCLUSION: KCNA5 displays little variability in its coding region. C
      terminal KCNA5 variants displayed near-normal gating but striking resistance to
      drug block; thus these pharmacogenomic studies have identified a heretofore
      unappreciated role of this region as a modulator of channel sensitivity to drugs.
      Resistance to I(Kur) blockers may be genetically determined.

PMID- 15735609
TI  - Implications of CYP2A6 genetic variation for smoking behaviors and nicotine
      dependence.
AB  - Nicotine is the primary addictive compound in tobacco smoke. In this review we
      summarize nicotine dependence and the genetics of smoking in brief before
      focusing on cytochrome P450 (CYP) 2A6. In humans nicotine is mainly inactivated
      to cotinine and CYP2A6 mediates approximately 90% of this conversion. Some, but
      not all, studies suggest that genetic variation in CYP2A6 may play a role in
      smoking. We review some of the recent findings on the influence of CYP2A6 genetic
      polymorphisms on nicotine kinetics, smoking behaviors, and how the gene appears
      to exert differential effects during various stages of smoking (eg, initiation,
      conversion to dependence, amount smoked during dependence, and quitting). These
      new findings will be put in the context of the discrepancies found in the
      literature. Implications of these recent findings on current and novel treatment
      approaches for smoking cessation and tobacco-related lung cancer will also be
      discussed.

PMID- 15735611
TI  - Effect of grapefruit juice volume on the reduction of fexofenadine
      bioavailability: possible role of organic anion transporting polypeptides.
AB  - OBJECTIVE: The purpose of this study was to elucidate the potential clinical
      relevance and mechanism(s) of action of 2 different volumes of grapefruit juice
      on the reduction of bioavailability of fexofenadine, a substrate of organic anion
      transporting polypeptides. METHODS: Grapefruit juice or water at normal (300 mL)
      or high (1200 mL) volume was ingested concomitantly with 120 mg fexofenadine by
      12 healthy volunteers in a randomized 4-way crossover study, and fexofenadine
      pharmacokinetics were determined over a period of 8 hours. RESULTS: The 300-mL
      volume of grapefruit juice decreased the mean area under the plasma drug
      concentration-time curve (AUC) and the peak plasma drug concentration of
      fexofenadine to 58% (P < .001) and 53% (P < .001), respectively, of those with
      the corresponding volume of water, and 1200 mL grapefruit juice reduced these
      parameters to 36% ( P < .001) and 33% ( P < .001), respectively, of those with
      the corresponding volume of water. The 300-mL volume of grapefruit juice
      diminished the AUC of fexofenadine variably among individuals. This decline
      correlated with baseline AUC of fexofenadine with water at equivalent volume
      (r(2) = 0.97, P < .0001). The 1200-mL volume of grapefruit juice decreased the
      AUC of fexofenadine more than the 300-mL volume of grapefruit juice compared with
      the corresponding volume of water in each subject by a constant amount.
      Grapefruit juice, 300 mL and 1200 mL, reduced the coefficient of variation of the
      AUC of fexofenadine by 2-fold compared with that with a matching volume of water.
      CONCLUSIONS: Grapefruit juice at a commonly consumed volume diminished the oral
      bioavailability of fexofenadine sufficiently to be pertinent clinically, likely
      by direct inhibition of uptake by intestinal organic anion transporting
      polypeptide A (OATP-A; new nomenclature, OATP1A2). A much higher volume caused an
      additional modest effect, possibly from reduced intestinal concentration and
      transit time of fexofenadine. This food-drug interaction appears to be novel and
      may be relevant to other fruit juices and drugs.

PMID- 15735610
TI  - Influence of menstrual cycle on cytochrome P450 2A6 activity and cardiovascular
      effects of nicotine.
AB  - BACKGROUND AND OBJECTIVES: The phase of the menstrual cycle has been reported to
      affect frequency of smoking, withdrawal symptoms, and the likelihood of smoking
      cessation in women. Cytochrome P450 (CYP) 2A6 is primarily responsible for the
      metabolism of nicotine. Our objective was to evaluate the effect of the phase of
      the menstrual cycle on the activity of CYP2A6 and the cardiovascular effects of
      nicotine. METHOD: Eleven healthy, nonsmoking women received a 30-minute combined
      infusion of deuterium-labeled nicotine and cotinine (0.5 microg . kg(-1) . min(
      1) of each compound) during the midfollicular and midluteal phases of the
      menstrual cycle. Nicotine and cotinine pharmacokinetic parameters and plasma
      adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine responses
      were measured over time. RESULTS: There were no biologically or statistically
      significant differences in the comparison of menstrual cycle phases with regard
      to the pharmacokinetics of nicotine and cotinine. Nicotine clearance was 1000 +/-
      315 mL/min and 1047 +/- 271 mL/min in the follicular and luteal phases,
      respectively (geometric mean ratio, 1.06; 90% confidence interval, 0.87-1.29).
      Cotinine clearance was 44 +/- 20 mL/min and 55 +/- 42 mL/min in the follicular
      and luteal phases, respectively (geometric mean ratio, 1.13; 90% confidence
      interval, 0.90-1.41). Nicotine infusion increased blood pressure, heart rate, and
      epinephrine concentrations. There were no differences in catecholamine, ACTH, or
      hemodynamic responses to nicotine infusion between menstrual cycle phases,
      although norepinephrine concentrations were constantly higher in the luteal phase
      compared with the follicular phase. CONCLUSIONS: CYP2A6 activity is not affected
      by menstrual cycle phase, and it is unlikely that menstrual cycle-related smoking
      habits of women are determined by changes in nicotine pharmacokinetics. The
      effects of nicotine on plasma ACTH and catecholamine levels and hemodynamic
      parameters are not altered by menstrual cycle phase in healthy, nonsmoking women.

PMID- 15735612
TI  - Inhibition of human intestinal wall metabolism by macrolide antibiotics: effect
      of clarithromycin on cytochrome P450 3A4/5 activity and expression.
AB  - BACKGROUND: Clarithromycin increases both hepatic and intestinal availability of
      the selective cytochrome P450 (CYP) 3A probe midazolam. This study was designed
      to identify determinants of variability in the extent of intestinal wall CYP3A
      inhibition by clarithromycin, such as CYP3A5 genotype, and the mechanism of
      inhibition. METHODS: Ten healthy volunteers received 500 mg oral clarithromycin
      twice a day for 7 days. Before and after administration of clarithromycin, small
      bowel mucosal biopsy specimens were obtained endoscopically. Intestinal CYP3A
      activity was determined from the rate of 1'-hydroxymidazolam and 4
      hydroxymidazolam formation by incubation of small-bowel homogenate with midazolam
      (25 micromol/L) and NADPH for 5 minutes. Intestinal CYP3A4 and CYP3A5 messenger
      ribonucleic acid was quantified by real-time reverse transcriptase-polymerase
      chain reaction. Intestinal CYP3A4 and CYP3A5 protein concentrations were
      determined by immunoblotting. Serum and homogenate concentrations of midazolam,
      clarithromycin, and metabolites were determined by liquid chromatography-mass
      spectrometry. CYP3A5 genotype was determined by real-time polymerase chain
      reaction. RESULTS: The formation of 1'-hydroxymidazolam (1.36 +/- 0.46 pmol .
      min(-1) . mg(-1) at baseline versus 0.35 +/- 0.16 pmol . min(-1) . mg(-1) after
      administration) and 4-hydroxymidazolam (0.39 +/- 0.12 pmol . min(-1) . mg(-1) at
      baseline versus 0.12 +/- 0.05 pmol . min(-1) . mg(-1) after administration) was
      significantly (P < .001) reduced after clarithromycin administration.
      Clarithromycin administration did not result in a significant change in
      intestinal CYP3A4 and CYP3A5 messenger ribonucleic acid and protein expression.
      All subjects had detectable serum clarithromycin concentrations after 7 days of
      clarithromycin (3.71 +/- 2.43 micromol/L). The mean concentration of
      clarithromycin in the intestinal biopsy homogenate was 1.2 +/- 0.7 nmol/L (range,
      0.42-2.39 nmol/L). Compared with CYP3A5 nonexpressers, subjects with at least 1
      CYP3A5*1 allele (CYP3A5 expressers) had greater inhibition of intestinal CYP3A
      activity after treatment with clarithromycin. There was a strong linear
      relationship between the decrease in intestinal CYP3A activity and baseline
      catalytic activity (R(2) = 0.9). CONCLUSION: Baseline intestinal activity of
      CYP3A4 was a key determinant of variability of the inhibitory effect of
      clarithromycin among individuals. CYP3A5*1 alleles were associated with greater
      baseline intestinal CYP3A activity and, therefore, greater extent of inhibition.
      The primary in vivo mechanism was not rapidly reversible competitive or
      irreversible inhibition but was likely formation of metabolic intermediate
      complexes.

PMID- 15735613
TI  - Association between adherence measurements of metoprolol and health care
      utilization in older patients with heart failure.
AB  - OBJECTIVE: Data from electronic dosing monitors and published pharmacokinetic
      parameters were used to derive medication adherence measures for immediate
      release metoprolol and examine their association with health care utilization of
      outpatients aged 50 years or older with heart failure. METHODS: We used a 1
      compartment model and published population pharmacokinetic parameters to estimate
      mean plasma metoprolol concentrations for patients treated for 6 to 12 months. In
      the absence of directly measured plasma concentrations, we calculated the
      intended mean plasma concentration (Cp'(ave)) under the assumption of perfect
      adherence to the prescribed dose and frequency of administration. Projected mean
      plasma concentrations (Cp(ave)) were estimated by use of data from recorded
      dosing times. In addition to taking adherence (percentage of dose taken) and
      scheduling adherence (percentage of doses taken on schedule), we calculated the
      deviation from the intended exposure (DeltaCp(ave) = Cp'(ave) - Cp(ave)) and the
      proportion of intended exposure achieved by the patient (Cp(ave) /Cp'(ave)). We
      assessed the association between the adherence measures and the numbers of
      emergency department visits and hospital admissions experienced by the patients.
      RESULTS: Patients (N = 80) were aged 62 +/- 8 years. Mean DeltaCp(ave) and
      Cp(ave)/Cp'(ave) were 7.9 ng/mL (SD, 10.7) and 0.6 (SD, 0.3), respectively. Log
      linear models adjusted for patient functional status indicated that greater
      deviation from the intended metoprolol exposure (DeltaCp(ave)) was associated
      with increased numbers of emergency department visits ( P < .0001) and hospital
      admissions (P < .0001). A higher proportion of intended exposure (Cp(ave)
      /Cp'(ave)) corresponded to a reduced number of emergency department visits (P =
      .0204) and hospital admissions (P = .0093). Taking adherence was univariately
      associated with both emergency department visits and hospital visits (P < .0001
      and P = .0010, respectively). Scheduling adherence was associated with the number
      of emergency department visits (P = .0181) but not with the number of hospital
      admissions (P = .1602). Model selection procedures consistently chose the
      proposed measures over taking adherence and scheduling adherence. CONCLUSION:
      Deviation from the intended exposure and proportion of intended exposure achieved
      by the patient are valid adherence measures for immediate-release metoprolol and
      are associated with health care utilization. The potential utility of these
      measures for other beta-adrenergic antagonists and perhaps other cardiovascular
      drugs should be investigated.

PMID- 15735615
TI  - Peginterferon alfa-2a does not alter the pharmacokinetics of methadone in
      patients with chronic hepatitis C undergoing methadone maintenance therapy.
AB  - OBJECTIVE: Our objective was to quantify the pharmacokinetics of methadone and
      the pharmacokinetics and pharmacodynamics of peginterferon alfa-2a (40 kd) in
      patients with chronic hepatitis C undergoing methadone maintenance therapy.
      METHODS: Adults with chronic hepatitis C who had been receiving a consistent
      methadone maintenance regimen for at least 3 months were eligible for this open
      label, multicenter, nonrandomized drug interaction study. All patients received
      180 microg subcutaneous peginterferon alfa-2a once weekly for 4 weeks and
      continued their methadone regimen. Serial blood samples were collected at
      baseline and immediately before and for up to 168 hours after study drug
      administration for the purposes of quantifying methadone and peginterferon alfa
      2a serum concentrations, measuring serum 2',5'-oligoadenylate synthetase
      activity, and determining hepatitis C virus ribonucleic acid levels. RESULTS:
      Twenty-four patients were enrolled. Methadone exposure, as measured by maximum
      serum concentration (C(max)) and area under the concentration-time curve (AUC)
      normalized to a 100-mg/d dose, after 4 doses of peginterferon alfa-2a increased
      by 10% to 15% when compared with baseline. The week 4/baseline ratio of the mean
      C(max) was 1.11 (90% confidence interval [CI], 1.02-1.22), and for AUC from time
      0 to 24 hours, the week 4/baseline ratio was 1.15 (90% CI, 1.08-1.23). The mean
      accumulation ratios (week 4/first dose) for C(max) and AUC from time 0 to 168
      hours of peginterferon alfa-2a were 2.1 and 2.3, respectively. CONCLUSIONS:
      Peginterferon alfa-2a does not appreciably alter the pharmacokinetics of
      methadone.

PMID- 15735614
TI  - BIBN4096BS antagonizes human alpha-calcitonin gene related peptide-induced
      headache and extracerebral artery dilatation.
AB  - BACKGROUND AND OBJECTIVE: Calcitonin gene-related peptide (CGRP) plays a pivotal
      role in migraine pathogenesis. BIBN4096BS is the first CGRP receptor antagonist
      available for human studies, and its efficacy in the acute treatment of migraine
      has been demonstrated. We investigated the ability of BIBN4096BS to inhibit human
      alphaCGRP (h-alphaCGRP)-induced headache and cerebral hemodynamic changes in
      healthy volunteers. METHODS: Ten healthy volunteers completed this double-blind,
      placebo-controlled crossover study with 2.5 mg BIBN4096BS and placebo as
      pretreatments before a 20-minute intravenous infusion of h-alphaCGRP (1.5
      microg/min). Transcranial Doppler ultrasonography was used to measure blood flow
      velocity in the middle cerebral artery (MCA); regional and global cerebral blood
      flow (CBF) was measured by xenon 133 inhalation single-photon emission computed
      tomography. The temporal and radial artery diameter was measured by high
      frequency ultrasound. Systemic hemodynamics, end-tidal partial pressure of carbon
      dioxide (PETCO(2)), and headache were monitored. RESULTS: Of the 10 volunteers, 6
      had a CGRP-induced headache during the in-hospital phase after placebo
      pretreatment but none after BIBN4096BS (P = .031). BIBN4096BS did not affect
      changes in the diameter of the MCA or changes in CBF induced by h-alphaCGRP.
      Vasodilatation of the extracranial arteries was, however, significantly inhibited
      (P < .001 for temporal artery and P = .001 for radial artery). CONCLUSIONS: These
      results show that BIBN4096BS effectively prevents CGRP-induced headache and
      extracerebral vasodilatation but does not significantly affect the induced
      cerebral hemodynamic changes.

PMID- 15735616
TI  - Disposition of cisapride appears to be influenced by P-glycoprotein in the mouse.

PMID- 15735617
TI  - Modulation of celecoxib pharmacokinetics by food in pediatric patients.

PMID- 15735618
TI  - Limited association of the 2988g > a single nucleotide polymorphism with CYP2D641
      in black subjects.

PMID- 15735619
TI  - The current management of rectal cancer.

PMID- 15735622
TI  - Taking the guesswork out of toxicology.

PMID- 15735628
TI  - New UK law allows stricter punishment of animal rights extremists.

PMID- 15735629
TI  - Questioning IACUC composition: is SOCRATES' reasoning correct? SOCRATES is
      unreasonable.

PMID- 15735630
TI  - Questioning IACUC composition: is SOCRATES' reasoning correct?

PMID- 15735631
TI  - Questioning IACUC composition: is SOCRATES' reasoning correct? Don't believe
      SOCRATES.

PMID- 15735632
TI  - Questioning IACUC composition: is SOCRATES' reasoning correct? Every IACUC can
      improve.

PMID- 15735633
TI  - Questioning IACUC composition: is SOCRATES' reasoning correct? SOCRATES was
      right.

PMID- 15735634
TI  - What's your diagnosis? Limb discoloration on a depressed tree frog (Hyla
      cinerea).

PMID- 15735636
TI  - Introduction to the Good Laboratory Practice Regulations.
AB  - The GLP Regulations provide the framework for performing scientifically valid
      studies and generating reliable safety data. Complying with these regulations is
      a complex process. The veterinary and animal care staff has a key role in
      supporting these studies.

PMID- 15735637
TI  - The role of a clinical veterinarian in a safety assessment testing facility.
AB  - A clinical veterinarian working in a safety assessment testing facility must
      balance animal welfare concerns with the attainment of sound, reproducible data
      necessary for regulatory studies. Drawing on her experience as a clinical
      veterinarian with specialty training in the field of toxicology, and past
      experience as a Study Director on safety assessment studies, the author describes
      practices that facilitate the veterinarian's role to ensure animal welfare on
      safety assessment studies.

PMID- 15735638
TI  - Food preferences of captive gray short-tailed opossums (Monodelphis domestica).
AB  - The gray short-tailed opossum has been a subject in behavioral and biomedical
      studies for the last quarter century, but researchers know little about its
      preferred diet. The authors describe a study designed to determine food
      preferences of this species for the purpose of identifying suitable rewards to be
      used in behavioral studies.

PMID- 15735639
TI  - Systematic discovery of regulatory motifs in human promoters and 3' UTRs by
      comparison of several mammals.
AB  - Comprehensive identification of all functional elements encoded in the human
      genome is a fundamental need in biomedical research. Here, we present a
      comparative analysis of the human, mouse, rat and dog genomes to create a
      systematic catalogue of common regulatory motifs in promoters and 3' untranslated
      regions (3' UTRs). The promoter analysis yields 174 candidate motifs, including
      most previously known transcription-factor binding sites and 105 new motifs. The
      3'-UTR analysis yields 106 motifs likely to be involved in post-transcriptional
      regulation. Nearly one-half are associated with microRNAs (miRNAs), leading to
      the discovery of many new miRNA genes and their likely target genes. Our results
      suggest that previous estimates of the number of human miRNA genes were low, and
      that miRNAs regulate at least 20% of human genes. The overall results provide a
      systematic view of gene regulation in the human, which will be refined as
      additional mammalian genomes become available.

PMID- 15735640
TI  - Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart.
AB  - Systemic gene delivery into muscle has been a major challenge for muscular
      dystrophy gene therapy, with capillary blood vessels posing the principle barrier
      and limiting vector dissemination. Previous efforts to deliver genes into
      multiple muscles have relied on isolated vessel perfusion or pharmacological
      interventions to enforce broad vector distribution. We compared the efficiency of
      multiple adeno-associated virus (AAV) vectors after a single injection via
      intraperitoneal or intravenous routes without additional intervention. We show
      that AAV8 is the most efficient vector for crossing the blood vessel barrier to
      attain systemic gene transfer in both skeletal and cardiac muscles of mice and
      hamsters. Serotypes such as AAV1 and AAV6, which demonstrate robust infection in
      skeletal muscle cells, were less effective in crossing the blood vessel barrier.
      Gene expression persisted in muscle and heart, but diminished in tissues
      undergoing rapid cell division, such as neonatal liver. This technology should
      prove useful for muscle-directed systemic gene therapy.

PMID- 15735641
TI  - Drosophila N-cadherin mediates an attractive interaction between photoreceptor
      axons and their targets.
AB  - Classical cadherins have been proposed to mediate interactions between pre- and
      postsynaptic cells that are necessary for synapse formation. We provide the first
      direct, genetic evidence in favor of this model by examining the role of N
      cadherin in controlling the pattern of synaptic connections made by photoreceptor
      axons in Drosophila. N-cadherin is required in both individual photoreceptors and
      their target neurons for photoreceptor axon extension. Cell-by-cell
      reconstruction of wild-type photoreceptor axons extending within mosaic patches
      of mutant target cells shows that N-cadherin mediates attractive interactions
      between photoreceptors and their targets. This interaction is not limited to
      those cells that will become the synaptic partners of photoreceptors. Multiple N
      cadherin isoforms are produced, but single isoforms can substitute for endogenous
      N-cadherin activity. We propose that N-cadherin mediates a homophilic, attractive
      interaction between photoreceptor growth cones and their targets that precedes
      synaptic partner choice.

PMID- 15735642
TI  - Self-administration enhances excitatory synaptic transmission in the bed nucleus
      of the stria terminalis.
AB  - Understanding the neurobiology of motivation might help in reducing compulsive
      behaviors such as drug addiction or eating disorders. This study shows that
      excitatory synaptic transmission was enhanced in the bed nucleus of the stria
      terminalis of rats that performed an operant task to obtain cocaine or palatable
      food. There was no effect when cocaine or food was delivered passively,
      suggesting that synaptic plasticity in this area is involved in reward-seeking
      behaviors.

PMID- 15735643
TI  - Amygdala damage impairs emotional memory for gist but not details of complex
      stimuli.
AB  - Neurobiological studies demonstrate the amygdala's role in emotional memory, and
      psychological studies suggest a particular pattern: enhanced memory for the gist
      but not the details of complex stimuli. We hypothesized that these two findings
      are related. Whereas normal (n = 52) and brain-damaged (n = 22) controls showed
      the expected enhancement of gist memory when the encoding context was emotional,
      persons with unilateral damage to the medial temporal lobe including the amygdala
      (n = 16) did not show this pattern. Furthermore, amygdala volume showed a
      significant positive correlation with gist memory but not with overall memory. A
      further study in four subjects with selective medial temporal damage sparing the
      amygdala, and one with selective damage confined to the amygdala, confirmed the
      specificity of this effect to the amygdala. The data support a model whereby the
      amygdala focuses processing resources on gist, possibly accounting for features
      of traumatic memories and eyewitness testimony in real life.

PMID- 15735644
TI  - Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy
      and sensorineural hearing loss.
AB  - We identified a human mutation that causes dilated cardiomyopathy and heart
      failure preceded by sensorineural hearing loss (SNHL). Unlike previously
      described mutations causing dilated cardiomyopathy that affect structural
      proteins, this mutation deletes 4,846 bp of the human transcriptional coactivator
      gene EYA4. To elucidate the roles of eya4 in heart function, we studied zebrafish
      embryos injected with antisense morpholino oligonucleotides. Attenuated eya4
      transcript levels produced morphologic and hemodynamic features of heart failure.
      To determine why previously described mutated EYA4 alleles cause SNHL without
      heart disease, we examined biochemical interactions of mutant Eya4 peptides. Eya4
      peptides associated with SNHL, but not the shortened 193-amino acid peptide
      associated with dilated cardiomyopathy and SNHL, bound wild-type Eya4 and
      associated with Six proteins. These data define unrecognized and crucial roles
      for Eya4-Six-mediated transcriptional regulation in normal heart function.

PMID- 15735645
TI  - Mutation in myosin heavy chain 6 causes atrial septal defect.
AB  - Atrial septal defect is one of the most common forms of congenital heart
      malformation. We identified a new locus linked with atrial septal defect on
      chromosome 14q12 in a large family with dominantly inherited atrial septal
      defect. The underlying mutation is a missense substitution, I820N, in alpha
      myosin heavy chain (MYH6), a structural protein expressed at high levels in the
      developing atria, which affects the binding of the heavy chain to its regulatory
      light chain. The cardiac transcription factor TBX5 strongly regulates expression
      of MYH6, but mutant forms of TBX5, which cause Holt-Oram syndrome, do not.
      Morpholino knock-down of expression of the chick MYH6 homolog eliminates the
      formation of the atrial septum without overtly affecting atrial chamber
      formation. These data provide evidence for a link between a transcription factor,
      a structural protein and congenital heart disease.

PMID- 15735646
TI  - Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome
      and limb abnormalities.
AB  - Autosomal dominant mutations in the gene encoding the basic helix-loop-helix
      transcription factor Twist1 are associated with limb and craniofacial defects in
      humans with Saethre-Chotzen syndrome. The molecular mechanism underlying these
      phenotypes is poorly understood. We show that ectopic expression of the related
      basic helix-loop-helix factor Hand2 phenocopies Twist1 loss of function in the
      limb and that the two factors have a gene dosage-dependent antagonistic
      interaction. Dimerization partner choice by Twist1 and Hand2 can be modulated by
      protein kinase A- and protein phosphatase 2A-regulated phosphorylation of
      conserved helix I residues. Notably, multiple Twist1 mutations associated with
      Saethre-Chotzen syndrome alter protein kinase A-mediated phosphorylation of
      Twist1, suggesting that misregulation of Twist1 dimerization through either
      stoichiometric or post-translational mechanisms underlies phenotypes of
      individuals with Saethre-Chotzen syndrome.

PMID- 15735647
TI  - Sarcoidosis is associated with a truncating splice site mutation in BTNL2.
AB  - Sarcoidosis is a polygenic immune disorder with predominant manifestation in the
      lung. Genome-wide linkage analysis previously indicated that the extended major
      histocompatibility locus on chromosome 6p was linked to susceptibility to
      sarcoidosis. Here, we carried out a systematic three-stage SNP scan of 16.4 Mb on
      chromosome 6p21 in as many as 947 independent cases of familial and sporadic
      sarcoidosis and found that a 15-kb segment of the gene butyrophilin-like 2
      (BTNL2) was associated with the disease. The primary disease-associated variant
      (rs2076530; P(TDT) = 3 x 10(-6), P(case-control) = 1.1 x 10(-8); replication
      P(TDT) = 0.0018, P(case-control) = 1.8 x 10(-6)) represents a risk factor that is
      independent of variation in HLA-DRB1. BTNL2 is a member of the immunoglobulin
      superfamily and has been implicated as a costimulatory molecule involved in T
      cell activation on the basis of its homology to B7-1. The G --> A transition
      constituting rs2076530 leads to the use of a cryptic splice site located 4 bp
      upstream of the affected wild-type donor site. Transcripts of the risk-associated
      allele have a premature stop in the spliced mRNA. The resulting protein lacks the
      C-terminal IgC domain and transmembrane helix, thereby disrupting the membrane
      localization of the protein, as shown in experiments using green fluorescent
      protein and V5 fusion proteins.

PMID- 15735648
TI  - Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine
      kinases.
AB  - Signaling-responsive MAP kinases (MAPKs) are key in mediating immune responses
      and are activated through the phosphorylation of a Thr-X-Tyr motif by upstream
      MAPK kinases. Here we show that T cells stimulated through the T cell receptor
      (TCR) used an alternative mechanism in which p38 was phosphorylated on Tyr323 and
      subsequently autophosphorylated residues Thr180 and Tyr182. This required the TCR
      proximal tyrosine kinase Zap70 but not the adaptor protein LAT, which was
      required for activation of extracellular signal-regulated protein kinase MAPKs.
      TCR activation of p38 lacking Tyr323 was diminished, and blocking of p38 activity
      prevented p38 dual phosphorylation in normal T cells but not in B cells. Thus,
      phosphorylation of Tyr323 dependent on the tyrosine kinase Lck and mediated by
      Zap70 serves as an important mechanism for TCR activation of p38 in T cells.

PMID- 15735649
TI  - The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38
      activation pathway.
AB  - The p38 MAP kinase (MAPK) is phosphorylated and activated by upstream MAPK
      kinases. T cells have an alternative pathway in which T cell receptor-activated
      tyrosine kinase Zap70 phosphorylates p38 on Tyr323. Mice lacking Gadd45alpha, a
      small p38-binding molecule, develop a lupus-like autoimmune disease. Here we show
      that resting T cells but not B cells from Gadd45a(-/-) mice had spontaneously
      increased p38 activity in the absence of 'upstream' MAPK kinase activation. The
      p38 from resting Gadd45a(-/-) T cells was spontaneously phosphorylated on Tyr323,
      and its activity was specifically inhibited by recombinant Gadd45alpha in vitro.
      Thus, constitutive activation of T cell p38 through the alternative pathway is
      prevented by Gadd45alpha, the absence of which results in p38 activation, T cell
      hyperproliferation and autoimmunity.

PMID- 15735650
TI  - Lack of prominent peptide-major histocompatibility complex features limits
      repertoire diversity in virus-specific CD8+ T cell populations.
AB  - Using both 'reverse genetics' and structural analysis, we have examined the in
      vivo relationship between antigenicity and T cell receptor (TCR) repertoire
      diversity. Influenza A virus infection of C57BL/6 mice induces profoundly
      different TCR repertoires specific for the nucleoprotein peptide of amino acids
      366-374 (NP366) and the acid polymerase peptide of amino acids 224-233 (PA224)
      presented by H-2D(b). Here we show the H-2D(b)-NP366 complex with a 'featureless'
      structure selected a limited TCR repertoire characterized by 'public' TCR usage.
      In contrast, the prominent H-2D(b)-PA224 complex selected diverse, individually
      'private' TCR repertoires. Substitution of the arginine at position 7 of PA224
      with an alanine reduced the accessible side chains of the epitope. Infection with
      an engineered virus containing a mutation at the site encoding the exposed
      arginine at position 7 of PA224 selected a restricted TCR repertoire similar in
      diversity to that of the H-2D(b)-NP366-specific response. Thus, the lack of
      prominent features in an antigenic complex of peptide and major
      histocompatibility complex class I is associated with a diminished spectrum of
      TCR usage.

PMID- 15735651
TI  - Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis.
AB  - Chronic progression of two T cell-mediated central nervous system (CNS)
      demyelinating models of multiple sclerosis, relapsing EAE (R-EAE) and Theiler's
      murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is
      dependent on the activation of T cells to endogenous myelin epitopes (epitope
      spreading). Using transfer of carboxyfluorescein succinyl ester (CFSE)-labeled T
      cell receptor (TCR)-transgenic T cells and mixed bone marrow chimeras, we show
      that activation of naive proteolipid protein (PLP)139-151-specific T cells in SJL
      mice undergoing PLP178-191-induced R-EAE or TMEV-IDD occurs directly in the CNS
      and not in the cervical lymph nodes or other peripheral lymphoid organs.
      Examination of the antigen-presentation capacity of antigen-presenting cell (APC)
      populations purified from the CNS of mice with PLP178-191-induced R-EAE shows
      that only F4/80-CD11c+CD45hi dendritic cells (DCs) efficiently present endogenous
      antigen to activate naive PLP139-151-specific T cells in vitro. In contrast, DCs
      as well as F4/80+CD45hi macrophages and F4/80+CD45lo microglia activate a PLP139
      151-specific helper T cell line. The data suggest that naive T cells enter the
      inflamed CNS and are activated by local APCs, possibly DCs, to initiate epitope
      spreading.

PMID- 15735652
TI  - Hypothalamic sensing of circulating fatty acids is required for glucose
      homeostasis.
AB  - Increased glucose production is a hallmark of type 2 diabetes and alterations in
      lipid metabolism have a causative role in its pathophysiology. Here we postulate
      that physiological increments in plasma fatty acids can be sensed within the
      hypothalamus and that this sensing is required to balance their direct
      stimulatory action on hepatic gluconeogenesis. In the presence of physiologically
      relevant increases in the levels of plasma fatty acids, negating their central
      action on hepatic glucose fluxes through (i) inhibition of the hypothalamic
      esterification of fatty acids, (ii) genetic deletion (Sur1-deficient mice) of
      hypothalamic K(ATP) channels or pharmacological blockade (K(ATP) blocker) of
      their activation by fatty acids, or (iii) surgical resection of the hepatic
      branch of the vagus nerve led to a marked increase in liver glucose production.
      These findings indicate that a physiological elevation in circulating lipids can
      be sensed within the hypothalamus and that a defect in hypothalamic lipid sensing
      disrupts glucose homeostasis.

PMID- 15735653
TI  - Dendritic cells permit immune invasion of the CNS in an animal model of multiple
      sclerosis.
AB  - Immunization with myelin antigens leads to the development of experimental
      autoimmune encephalomyelitis, an animal model of multiple sclerosis. The disease
      can also be induced by the transfer of encephalitogenic CD4+ T helper (T(H))
      lymphocytes into naive mice. These T cells need to re-encounter their cognate
      antigen in the context of major histocompatibility complex (MHC) class II-bearing
      antigen-presenting cells (APCs) in order to recognize their target. The cell type
      and location of the APC mediating T-cell entry into the central nervous system
      (CNS) remain unknown. Here, we show that APCs of the lymphoreticular system and
      of the CNS parenchyma are dispensable for the immune invasion of the CNS. We also
      describe that a discrete population of vessel-associated dendritic cells (DCs) is
      present in human brain tissue. In mice, CD11c+ DCs alone are sufficient to
      present antigen in vivo to primed myelin-reactive T cells in order to mediate CNS
      inflammation and clinical disease development.

PMID- 15735654
TI  - The mechanism underlying the contractile effect of a chemotactic peptide, formyl
      Met-Leu-Phe on the guinea-pig Taenia coli.
AB  - 1 The contractile mechanism of N-formyl-L-methionyl-L-leucyl-L-phenylalanine
      (fMLP) was investigated in the guinea-pig Taenia coli, by simultaneously
      monitoring the changes in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and
      force. 2 fMLP induced a significant elevation of [Ca(2+)](i) and force at
      concentrations higher than 10 nM. The maximal response was obtained at a
      concentration of higher than 1 microM. 3 fMLP (10 microM) augmented the force
      development induced by a stepwise increment of the extracellular Ca(2+)
      concentration during 60 mM K(+) depolarization, while it had no effect on the
      [Ca(2+)](i) elevation, and thus produced a greater force for a given elevation of
      [Ca(2+)](i) than 60 mM K(+) depolarization. 4 The removal of extracellular Ca(2+)
      completely abolished the fMLP-induced contraction. The fMLP-induced [Ca(2+)](i)
      elevation was inhibited substantially but not completely by 10 microM diltiazem,
      partly by 10 microM SK&F 96365, and completely by their combination. 5 Y27632, a
      specific inhibitor of rho-kinase, had no significant effect on the fMLP-induced
      [Ca(2+)](i) elevation and force development. 6 Chenodeoxycholic acid, a formyl
      peptide receptor antagonist, specifically abolished the fMLP-induced contraction
      but not high K(+)- or carbachol-induced contractions. 7 A dual
      lipoxygenase/cyclooxygenase inhibitor, a 5-lipoxygenase inhibitor, a nonselective
      leukotriene receptor antagonist, and a selective type 1 cysteinyl-containing
      leukotriene receptor antagonist specifically reduced the fMLP-induced
      contraction. 8 We suggest that the low-affinity-type fMLP receptor and
      lipoxygenase metabolites of arachidonic acid are involved in the fMLP-induced
      contraction in the guinea-pig T. coli. This contraction mainly depends on the
      [Ca(2+)](i) elevation due to Ca(2+) influx and the enhancement of Ca(2+)
      sensitivity in the contractile apparatus.

PMID- 15735655
TI  - Purinergic modulation of cardiovascular function in the rat locus coeruleus.
AB  - 1 The purpose of the present study was to determine whether purines exerted a
      physiological role in central cardiovascular modulation at the level of the locus
      coeruleus (LC). 2 In pentobarbitone-anaesthetised Wistar-Kyoto rats, unilateral
      microinjection of ATP or alpha,beta-methyleneATP into the LC elicited dose
      related decreases in blood pressure and heart rate. Unilateral microinjection of
      the P2 purinoceptor antagonists suramin and PPADS, caused pressor and tachycardic
      responses. Administration of the selective P2X(1) receptor antagonist NF-279 had
      no effect. While both ATP and L-glutamate (L-GLU) resulted in depressor responses
      after intra-LC microinjection, following intra-LC microinjection of P2
      purinoceptor antagonists into the LC, the effects of subsequent administration of
      either ATP or L-GLU were functionally reversed, such that a pressor response
      ensued. 3 Microinjection of noradrenaline into the LC caused an increase in blood
      pressure and heart rate; however, the alpha(2)-adrenoceptor antagonist idazoxan
      had no cardiovascular effects, but did prevent the pressor response to PPADS or
      suramin. In addition, coinjection of idazoxan with either suramin or PPADS
      abolished the ATP and L-GLU mediated pressor responses observed following either
      suramin or PPADS administration. 4 The present data suggest that firstly, purines
      are capable of acting within the LC to ultimately modulate the cardiovascular
      system and secondly, that there is apparently a functional interaction between
      tonically active purinergic and noradrenergic systems within the LC of the rat.

PMID- 15735657
TI  - Ceramide alters endothelial cell permeability by a nonapoptotic mechanism.
AB  - Ceramide is a lipid second messenger that was recently identified as mediator of
      pulmonary edema in vivo. Here, we investigated the effect of ceramide on the
      permeability of confluent endothelial cell monolayers. In monolayers of bovine
      pulmonary artery and human microvascular pulmonary endothelial cells, incubation
      with C6-ceramide for 3 h elevated permeability in a concentration-dependent
      manner, whereas dihydroceramide was without effect. After 3 h of incubation with
      ceramide, we found no signs of necrosis (release of lactate dehydrogenase, loss
      of thiazylyl blue reduction) or apoptosis (ssDNA, caspase-8 activity). The
      increased endothelial permeability in response to ceramide was attenuated by the
      Ser/Thr protein kinase inhibitors K252a, K252b and H-7, as well as by the
      phosphatidylinositol-specific phospholipase C inhibitor L108. Since in some
      systems sphingosine-1-phosphate (S1P) acts antagonistic to ceramide, the effect
      of S1P was studied. S1P transiently increased endothelial cell resistance,
      whether it was given together with ceramide or 90 min thereafter. These data
      provide a novel example of the antagonism between S1P and ceramide. Our findings
      further suggest that ceramide alters vascular permeability by activation of
      pathways dependent on unidentified phospholipase C and Ser/Thr kinase isoenzymes.

PMID- 15735656
TI  - Stimulus-dependent glucocorticoid-resistance of GM-CSF production in human
      cultured airway smooth muscle.
AB  - For a subpopulation of asthmatics, symptoms persist even with high doses of
      glucocorticoids. Glucocorticoids reduce the levels of the proinflammatory and
      fibrogenic cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF)
      produced by human cultured airway smooth muscle (ASM). We have contrasted the
      effects of a synthetic glucocorticoid, dexamethasone, on thrombin- and IL-1alpha
      stimulated GM-CSF production in human ASM cells. Although IL-1alpha stimulated
      three-fold higher levels of GM-CSF mRNA and protein compared to thrombin,
      dexamethasone concentration-dependently reduced IL-1alpha-stimulated GM-CSF more
      potently and to a greater extent than the response to thrombin. This pattern of
      glucocorticoid regulation was also observed at the GM-CSF mRNA level and was
      reproduced with other glucocorticoids such as fluticasone propionate. IL-1alpha
      and thrombin stimulated NF-kappa B-dependent luciferase expression equally.
      Dexamethasone treatment reduced luciferase expression stimulated by both IL
      1alpha and thrombin. The GM-CSF mRNA half life was markedly prolonged by IL
      1alpha compared to thrombin. This IL-1alpha-induced GM-CSF mRNA stability was
      prevented by either dexamethasone or the p38(MAPK) inhibitor, SB203580, neither
      of which influenced GM-CSF mRNA stability in thrombin-treated cells.
      Dexamethasone inhibited p38(MAPK) phosphorylation in IL-1alpha-stimulated ASM,
      whereas thrombin does not stimulate p38(MAPK) phosphorylation. These data suggest
      that the mechanism underlying the greater potency and efficacy of glucocorticoids
      in reducing GM-CSF synthesis stimulated by IL-1alpha depends on inhibition of the
      involvement of p38(MAPK)-induced increases in GM-CSF message stability.

PMID- 15735658
TI  - Mechanisms of inverse agonist action at D2 dopamine receptors.
AB  - Mechanisms of inverse agonist action at the D2(short) dopamine receptor have been
      examined. Discrimination of G-protein-coupled and -uncoupled forms of the
      receptor by inverse agonists was examined in competition ligand-binding studies
      versus the agonist [3H]NPA at a concentration labelling both G-protein-coupled
      and -uncoupled receptors. Competition of inverse agonists versus [3H]NPA gave
      data that were fitted best by a two-binding site model in the absence of GTP but
      by a one-binding site model in the presence of GTP. K(i) values were derived from
      the competition data for binding of the inverse agonists to G-protein-uncoupled
      and -coupled receptors. K(coupled) and K(uncoupled) were statistically different
      for the set of compounds tested (ANOVA) but the individual values were different
      in a post hoc test only for (+)-butaclamol. These observations were supported by
      simulations of these competition experiments according to the extended ternary
      complex model. Inverse agonist efficacy of the ligands was assessed from their
      ability to reduce agonist-independent [35S]GTP gamma S binding to varying degrees
      in concentration-response curves. Inverse agonism by (+)-butaclamol and spiperone
      occurred at higher potency when GDP was added to assays, whereas the potency of (
      )-sulpiride was unaffected. These data show that some inverse agonists ((+)
      butaclamol, spiperone) achieve inverse agonism by stabilising the uncoupled form
      of the receptor at the expense of the coupled form. For other compounds tested,
      we were unable to define the mechanism.

PMID- 15735659
TI  - Diffuse alveolar hemorrhage following gemtuzumab ozogamicin.

PMID- 15735660
TI  - Allogeneic stem cell transplantation in second rather than first complete
      remission in selected patients with good-risk acute myeloid leukemia.
AB  - Through two consecutive trials, a policy that considered allogeneic stem cell
      transplantation (SCT) from a sibling donor in second rather than first complete
      remission (CR) in selected younger patients with acute myeloid leukemia (AML)
      with t(8;21)/inv(16) (core binding factor (CBF) group) or a normal karyotype (NN
      group) was followed by Acute Leukemia French Association (ALFA) centers. The
      outcome of 92 of these patients in first relapse (32 CBF, 60 NN) was reviewed
      with the aim of validating this strategy. The presence of an FLT3 internal tandem
      duplication (ITD) was retrospectively assessed in 50 patients. A total of 61
      patients (66%) reached a second CR. Donor availability was an independent
      prognostic factor for survival in the whole patient population as well as in the
      CBF subset, but not in NN patients, further supporting this strategy for CBF
      AMLs. In NN patients, FLT3-ITD was the main bad-prognosis factor for second CR
      achievement and survival, leading to consider SCT earlier, at least in FLT3-ITD
      patients with a donor.

PMID- 15735662
TI  - Maintaining high autopsy rates in a Canadian blood and marrow transplant program:
      preserving a diagnostic and research tool.
AB  - Autopsy series have revealed patterns of injury in graft-versus-host disease and
      provided insight into infectious and toxic complications following hematopoietic
      stem cell transplantation (HSCT). Overall autopsy rates have declined
      significantly in recent decades including specialized services such as neonatal
      medicine and cardiac care. However, rates of post-mortem exams at HSCT centers
      have not been specifically documented. We reviewed hospital records between 1992
      and 2002 to determine overall autopsy rates at our hospital and within the HSCT
      program. Although the overall autopsy rate declined steadily from 24% in 1992 to
      9% in 2002, rates of post-mortem exams in the HSCT program remained relatively
      stable at 32% (24-46%). Autopsy rates were not significantly different for
      recipients of allogeneic vs autologous transplants and no clear difference was
      observed for the proportion of autopsies requested on weekdays compared with
      weekends. Autopsies confirmed major clinical diagnoses and/or suspected causes of
      death in 45 of 61 autopsies (74%) and yielded major or minor disagreements in
      clinical diagnosis in 10 cases (16%) and seven cases (11%), respectively. The
      preservation of high rates of autopsy within our HSCT program demonstrates that
      specialized programs are able to maintain elevated rates of post-mortem
      examinations despite overall declining rates.

PMID- 15735661
TI  - Non-total body irradiation containing preparative regimen in alternative donor
      bone marrow transplantation for severe aplastic anemia.
AB  - Using non-total body irradiation (TBI) containing preparative regimens, 13
      patients with severe aplastic anemia (SAA) were transplanted from an alternative
      donor in a single institute. In total, 12 donors were unrelated volunteers and
      one was an HLA one-locus mismatched sibling. Median time from diagnosis of SAA to
      bone marrow transplantation (BMT) was 10.1 months (range, 1.6-180.1). Nine
      patients had received immunosuppressive treatment with ATG before BMT, while four
      had not. Preparative regimens consisted of cyclophosphamide plus ATG in nine
      patients, cyclophosphamide plus fludarabine in two patients, and cyclophosphamide
      plus fludarabine plus ATG in two patients. All patients received non-T-cell
      depleted bone marrow from the donor. Cyclosporine plus methotrexate were given
      for GVHD prophylaxis. All patients engrafted on a median of day 21 (range, 15
      27). Grade III-IV acute GVHD developed in three (23%) of 13 patients and
      extensive chronic GVHD in four (31%) of 12 evaluable patients. With a median
      follow-up duration of 1138 days (range, 118-1553), 10 patients are alive with
      durable engraftment showing 74.6% (95% confidence interval, 49.5-99.7%) of
      survival rate. Cause of the deaths was CNS bleeding in one and chronic GVHD in
      two. In conclusion, non-TBI containing preparative regimen could ensure durable
      engraftment in alternative donor BMT for SAA and showed promising results.

PMID- 15735663
TI  - A functional interaction between ATF7 and TAF12 that is modulated by TAF4.
AB  - The ATF7 proteins, which are members of the cyclic AMP responsive binding protein
      (CREB)/activating transcription factor (ATF) family of transcription factors,
      display quite versatile properties: they can interact with the adenovirus E1a
      oncoprotein, mediating part of its transcriptional activity; they heterodimerize
      with the Jun, Fos or related transcription factors, likely modulating their DNA
      binding specificity; they also recruit to the promoter a stress-induced protein
      kinase (JNK2). In the present study, we investigate the functional relationships
      of ATF7 with hsTAF12 (formerly hsTAF(II)20/15), which has originally been
      identified as a component of the general transcription factor TFIID. We show that
      overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation
      through direct interaction with ATF7, suggesting that TAF12 is a functional
      partner of ATF7. In support of this conclusion, chromatin immunoprecipitation
      experiments confirm the interaction of ATF7 with TAF12 on an ATF7-responsive
      promoter, in the absence of any artificial overexpression of both proteins. We
      also show that the TAF12-dependent transcriptional activation is competitively
      inhibited by TAF4. Although both TAF12 isoforms (TAF12-1 and -2, formerly
      TAF(II)20 and TAF(II)15) interact with the ATF7 activation region through their
      histone-fold domain, only the largest, hsTAF12-1, mediates transcriptional
      activation through its N-terminal region.

PMID- 15735664
TI  - The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly
      via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced
      lamellipodium formation, cell scattering and cell spreading.
AB  - Recently, evidence has been accumulating that inositol and phosphatidylinositol
      polyphosphate play important roles in a variety of signal transduction systems
      including membrane traffic, actin cytoskeleton rearrangement and cell motility.
      In this paper, we show for the first time that the SH2-domain-containing inositol
      5-phosphatase (SHIP)-2 binds directly to the hepatocyte growth factor (HGF/SF)
      receptor, c-Met, via phosphotyrosine 1356. HGF induces the breakdown of cell
      junctions and the dispersion of colonies of epithelial cells including MDCK
      cells. Whereas only few lamellipodia are observed in MDCK cells 2 min after
      stimulation with HGF, both SHIP-2- and SHIP-1-overexpressing cells form large,
      broad lamellipodia. The number of lamellipodia is 2-4-fold greater than that of
      mock-transfected MDCK cells in the same time period and SHIP is found to
      colocalize with actin at the leading edge. Furthermore, overexpression of a
      catalytic inactive mutant of SHIP-2 suppresses HGF-potentiated cell scattering
      and cell spreading, although these mutant-expressing cells form enhanced number
      of lamellipodia 2 min after HGF stimulation. Interestingly, cells expressing a
      mutant lacking the proline-rich domain of SHIP-2 at the C-terminal form few
      lamellipodia, but still spread and scatter upon stimulation with HGF at a reduced
      rate. These data suggest that phosphatase activity is required for HGF-mediated
      cell spreading and scattering but not for alteration of lamellipodium formation,
      while the proline-rich region influences lamellipodium formation. Furthermore,
      treatment with 10 microM of phosphatidylinositol 3 (PI3) kinase inhibitor,
      LY294002, abrogates HGF-induced cell scattering of SHIP-2-overexpressing cells
      but not parental HEK293 cells, suggesting that a balance between PI3 kinase and
      SHIP is important for cell motility.

PMID- 15735665
TI  - topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator
      of p53 in growth suppression induced by DNA damage.
AB  - The RING family zinc-finger protein topors (topoisomerase I-binding protein)
      binds not only topoisomerase I, but also p53 and the AAV-2 Rep78/68 proteins.
      topors maps to human chromosome 9p21, which contains candidate tumor suppressor
      genes implicated in small cell lung cancers. In this study, we isolated the
      murine counterpart of topors and investigated its impact on p53 function. The
      deduced amino-acid sequence of mouse topors exhibits extensive similarity to
      human topors. Overexpressed myc-tagged topors associates with and stabilizes p53,
      and enhances the p53-dependent transcriptional activities of p21(Waf1), MDM2 and
      Bax promoters and elevates endogenous p21(Waf1) mRNA levels. Overexpression of
      topors consequently results in the suppression of cell growth by cell cycle
      arrest and/or by the induction of apoptosis. Taken together, these studies
      identify topors as a positive regulator of p53. The expression of topors is
      induced by exposure to the genotoxic reagents cisplatin and camptothecin, a DNA
      topoisomerase I inhibitor. We therefore postulate that topors mediates p53
      dependent cellular responses induced by DNA damage, suggesting its physiological
      role as a tumor suppressor.

PMID- 15735666
TI  - Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA
      damage-induced apoptosis.
AB  - Human Kruppel-like factor 2 (KLF2) is a Cys(2)/His(2) zinc-finger-containing
      transcriptional factor, which is involved in multiple cellular pathways.
      Utilizing gene expression profiling to identify aberrantly expressed genes in
      ovarian cancer, we found that KLF2 was significantly and specifically
      downregulated in ovarian tumors. After reintroducing KLF2 into ovarian cancer
      cell lines, we observed decreased cell growth and increased sensitivity to DNA
      damage-induced apoptosis. Analysis of genes that could be potential targets of
      KLF2 revealed that KLF2 negatively regulated WEE1 expression. WEE1 encodes a
      tyrosine kinase that regulates the G2/M cell cycle transition. Expression of KLF2
      markedly repressed the transcription of WEE1 by directly binding to an SP1/CPBP
      motif located between -252 bp and the start codon of the WEE1 promoter. Both
      activation and zinc-finger domains of KLF2 were required for this suppression of
      Wee1 expression. In addition, we demonstrated that Wee1 expression prevents
      cancer cells from undergoing apoptosis in response to DNA damage; however, this
      resistance was abolished by coexpression of KLF2, which inhibits WEE1
      transcription. Thus, the level of WEE1 is regulated by KLF2 and enhanced KLF2
      expression sensitizes cells to DNA damage-induced apoptosis.

PMID- 15735667
TI  - Adhesion control of cyclin D1 and p27Kip1 levels is deregulated in melanoma cells
      through BRAF-MEK-ERK signaling.
AB  - Mutations in BRAF, a component of extracellular signal-regulated kinases 1 and 2
      (ERK) cascade, are frequent in melanoma. It is important to understand how BRAF
      mutations contribute to malignant traits including anchorage- and growth factor
      independence. We have previously shown that efficient activation of ERK in normal
      human epidermal melanocytes (NHEM) requires both adhesion to the extracellular
      matrix and growth factors. Mutant V599E BRAF is sufficient to promote ERK
      activation independent of adhesion and growth factors. Here, we analysed
      regulation of G1 cell cycle events in NHEM and human melanoma cells. We show that
      S phase entry in NHEM requires both adhesion and growth factor signaling through
      the MEK-ERK pathway. This control correlates with induction of cyclin D1 and
      downregulation of p27Kip1, two key G1 cell cycle events. In melanoma cells
      expressing V599E BRAF, cyclin D1 was constitutively expressed independent of
      adhesion but dependent upon MEK activation and nuclear accumulation of ERK.
      Reduction of cyclin D1 levels by RNA interference inhibited S phase entry in
      melanoma cells. Importantly, expression of V599E BRAF in NHEM was sufficient to
      promote cyclin D1 promoter activity in the absence of adhesion. Additionally,
      p27Kip1 levels were downregulated in V599E BRAF-expressing melanoma cells and
      active BRAF was sufficient to downregulate p27Kip1 in serum-starved NHEM. Thus,
      adhesion-growth factor cooperation, leading to efficient activation of ERK,
      regulates cyclin D1 and p27Kip1 levels in human melanocytes and mutant BRAF
      overrides adhesion-growth factor control of these two G1 cell cycle proteins in
      melanomas. These findings provide important insight into how BRAF mutations
      contribute to aberrant human melanocyte proliferation.

PMID- 15735668
TI  - Human endogenous retrovirus rec interferes with germ cell development in mice and
      may cause carcinoma in situ, the predecessor lesion of germ cell tumors.
AB  - Germ cell tumors (GCTs) are among the most common malignancies in young men. We
      have previously documented that patients with GCT frequently produce serum
      antibodies directed against proteins encoded by human endogenous retrovirus
      (HERV) type K sequences. Transcripts originating from the env gene of HERV-K,
      including the rec-relative of human immunodeficiency virus rev, are highly
      expressed in GCTs. We report here that mice that inducibly express HERV-K rec
      show a disturbed germ cell development and may exhibit, by 19 months of age,
      changes reminiscent of carcinoma in situ, the predecessor lesion of classic
      seminoma in humans. This provides the first direct evidence that the expression
      of a human endogenous retroviral gene previously established as a marker in human
      germ cell tumors may contribute to organ-specific tumorigenesis in a transgenic
      mouse model.

PMID- 15735669
TI  - De novo DNA methyltransferases Dnmt3a and Dnmt3b primarily mediate the cytotoxic
      effect of 5-aza-2'-deoxycytidine.
AB  - The deoxycytidine analog 5-aza-2'-deoxycitidine (5-aza-dC) is a potent
      chemotherapeutic agent effective against selective types of cancer. The molecular
      mechanism by which 5-aza-dC induces cancer cell death, however, is not fully
      understood. It has been accepted that the mechanism of toxicity is due to the
      covalent binding between the DNA methyltransferase (Dnmt) and 5-aza-dC
      substituted DNA. In order to define which member of the Dnmt family plays a
      dominant role in the cytotoxicity, we examined the effect of 5-aza-dC on cell
      growth and apoptosis in various Dnmt null mutant embryonic stem (ES) cells. Of
      interest, Dnmt3a-Dnmt3b double null ES cells were highly resistant to 5-aza-dC
      when compared to wild type, Dnmt3a null, Dnmt3b null, or Dnmt1 null ES cells. The
      cellular sensitivity to 5-aza-dC correlated well with the expression status of
      Dnmt3 in both undifferentiated and differentiated ES cells. When exogenous Dnmt3a
      or Dnmt3b was expressed in double null ES cells, the sensitivity to 5-aza-dC was
      partially restored. These results suggest that the cytotoxic effect of 5-aza-dC
      may be mediated primarily through Dnmt3a and Dnmt3b de novo DNA
      methyltransferases. Further, the ability to form Dnmt-DNA adducts was similar in
      Dnmt1 and Dnmt3, and the expression level of Dnmt3 was not higher than that of
      Dnmt1 in ES cells. Therefore, Dnmt3-DNA adducts may be more effective for
      inducing apoptosis than Dnmt1-DNA adducts. These results imply a therapeutic
      potential of 5-aza-dC to cancers expressing Dnmt3.

PMID- 15735671
TI  - Brca2 deficiency in the murine small intestine sensitizes to p53-dependent
      apoptosis and leads to the spontaneous deletion of stem cells.
AB  - The gene encoding the human BRCA2 tumour suppressor is mutated in a number of
      different tumour types, most notably inherited breast cancers. The primary role
      of BRCA2 is thought to lie in the maintenance of genomic stability via its role
      in the homologous recombination pathway. We generated mice in which Brca2 was
      deleted from virtually all cells within the adult small intestine, using a CYP1A1
      driven Cre-Lox approach. We noted a significant p53-dependent increase in the
      levels of spontaneous apoptosis which persisted for several months after removal
      of the gene and ultimately we observed the spontaneous deletion of Brca2
      deficient stem cells. Brca2 deficiency did not lead to gross changes in
      intestinal physiology but did enhance sensitivity to a variety of DNA
      crosslinking agents. Taken together, our results indicate that Brca2 plays an
      important role in the response to DNA damage in the small intestine. Furthermore,
      we show that Brca2 deficiency results in the spontaneous deletion of stem cells,
      thereby protecting the small intestine against tumorigenesis.

PMID- 15735670
TI  - Expression of EGF-family receptors and amphiregulin in multiple myeloma.
      Amphiregulin is a growth factor for myeloma cells.
AB  - A hallmark of plasma cells is the expression of syndecan-1, which has major
      functions in epithelial cells, in particular as the coreceptor of heparin-binding
      growth factors. We previously found that heparin-binding epidermal growth factor
      like growth factor (HB-EGF) is a growth factor for malignant plasma cells. As
      amphiregulin (AREG) is another heparin-binding factor of the EGF family, we
      investigated its role in multiple myeloma (MM). Using Affymetrix DNA microarrays,
      we show here that the AREG gene was expressed by purified primary myeloma cells
      from 65 patients and that the expression was higher than in normal bone marrow
      (BM) plasma cells or plasmablastic cells. AREG stimulated IL-6 production and
      growth of BM stromal cells. Using real-time reverse transcriptase-polymerase
      chain reaction, we found that MM cells expressed ErbB receptors and that AREG
      promoted their growth. Furthermore, PD169540 (a pan-ErbB inhibitor) and IRESSA
      (an ErbB1-specific inhibitor) induced apoptosis of primary myeloma cells from
      10/14 and 4/14 patients, respectively, and there was a synergistic effect with
      dexamethasone. Altogether, our data provide strong evidence that AREG plays an
      important role in the biology of MM and emphasize the advantages of using ErbB
      inhibitors, which might target myeloma cells as well as the tumor environment.

PMID- 15735672
TI  - PHOX2B mutations and genetic predisposition to neuroblastoma.
AB  - Neuroblastoma (NB) is a childhood malignancy originating from neural crest cells,
      which seldom occurs in association with other neurocristopathies. Owing to the
      rarity of familial NB cases, only a few linkage data are available and no
      mutations in candidate genes have been demonstrated up till now. Germline
      mutations in a small proportion of NB patients have been recently reported in the
      paired-like homeobox 2B (PHOX2B) gene, suggesting its role in NB predisposition.
      On the basis of this indication, we screened three Italian families with
      recurrence of NB and one family with occurrence of ganglioneuroblastoma and
      isolated Hirschsprung disease for PHOX2B defects. Our analysis did not show any
      mutation, excluding PHOX2B as the NB susceptibility gene in the families we
      analysed. Our findings combined with those derived from other PHOX2B mutation
      screenings and from genome-wide linkage analysis support a remarkable genetic
      heterogeneity of NB and suggest an oligogenic model of disease transmission.
      Furthermore, as PHOX2B mutations were mainly observed in some NB families with
      multifocal and syndromic NB, features that are missing in the families we have
      studied, we suggest they represent second-site modifications responsible for a
      specific phenotype rather than causal mutations of a major locus.

PMID- 15735673
TI  - The dioxin/aryl hydrocarbon receptor mediates downregulation of osteopontin gene
      expression in a mouse model of gastric tumourigenesis.
AB  - The dioxin/aryl hydrocarbon receptor functions as a ligand-activated
      transcription factor regulating transcription of a battery of genes encoding
      primarily drug-metabolizing enzymes. Expression of a constitutively active mutant
      of the aryl hydrocarbon receptor (CA-AhR) in transgenic mice results in
      development of stomach tumours, correlating with increased mortality. We have
      used suppression subtractive hybridization techniques followed by macroarray
      analysis to elucidate which genes are differentially expressed during this
      process. In the glandular stomach of CA-AhR mice, we observed decreased mRNA
      expression of osteopontin (OPN), a noncollagenous protein of bone matrix that is
      also involved in several important functions including regulation of cytokine
      production, macrophage accumulation, cell motility and adhesion. Downregulated
      expression of OPN during tumour development was confirmed by RT-PCR and RNA blot
      analysis. Immunohistochemical analysis showed that this decrease was confined to
      the corpus region, correlating with the restricted localization of the tumours.
      Decreased OPN mRNA expression was also observed in other organs of CA-AhR mice.
      Taken together, these results show that OPN is negatively regulated by the dioxin
      receptor, and that downregulation of its expression correlates with development
      of stomach tumours in mice expressing a constitutively active mutant of dioxin
      receptor.

PMID- 15735674
TI  - ILK mediates actin filament rearrangements and cell migration and invasion
      through PI3K/Akt/Rac1 signaling.
AB  - One of the hallmarks of integrin signaling is an increase in cell migration and
      invasion, both of which are associated with actin filament rearrangements.
      Integrin-linked kinase (ILK) is a cytoplasmic effector of integrin receptors. ILK
      is known to be involved in multiple cellular functions. However, the signaling
      pathways involved in ILK-mediated cellular structure and motility remain to be
      elucidated. Here, we have demonstrated that overexpression of ILK was sufficient
      to induce actin filament rearrangements, to form cell motility structures, and to
      increase cell migration and invasion in a phosphatidylinositol 3-kinase (PI3K)
      dependent manner. This corresponds with the activation of both Akt and p70
      ribosomal protein S6 kinase (p70S6K1). Overexpression of dominant-negative
      mutants of Akt inhibited ILK-dependent activation of p70S6K1, indicating that Akt
      is upstream of p70S6K1 in response to ILK signaling. Overexpression of ILK was
      sufficient to induce Rac1 activation, which was abolish by a PI3K inhibitor,
      indicating that Rac1 activity is involved in ILK signaling in a PI3K dependent
      manner. Inhibition of Akt, Rac1, or p70S6K1 inhibited the effects of ILK on actin
      filaments and cell migration, suggesting a regulatory role of the
      PI3K/Akt/p70S6K1/Rac1 signaling pathway in response to ILK signaling. We have
      shown that overexpression of a dominant-negative ILK was sufficient to abolish
      fibronectin peptide (PHSRN)-induced rearrangements of actin filaments and cell
      migration and invasion. Taken together, our results identify a mechanism through
      which ILK can regulate both integrin-associated rearrangements of actin filaments
      and cell migration and invasion at the integrin receptor-proximal region.

PMID- 15735675
TI  - Domain-specific function of ShcC docking protein in neuroblastoma cells.
AB  - ShcC is a family member of the Shc docking proteins that possess two different
      phosphotyrosine-binding motifs and conduct signals as Grb2-binding substrates of
      various receptor tyrosine kinases. We have recently shown that some neuroblastoma
      cell lines, such as NB-39-nu cells, express a protein complex of
      hyperphosphorylated ShcC and anaplastic lymphoma kinase (ALK), which is self
      activated by gene amplification. Here, we demonstrate that the expression of a
      mutant ShcC lacking Grb2-binding sites, 3YF-ShcC, significantly impaired the
      survival, differentiation and motility of NB-39-nu cells by blocking the ERK and
      Akt pathways. On the other hand, cells overexpressing ShcC or 3YF-ShcC, but not a
      mutant ShcC that lacks SH2, showed decreased anchorage independency and in vivo
      tumorigenicity, suggesting a novel ShcC-specific suppressive effect through its
      SH2 domain on cell transformation. Notably, overexpression of ShcC suppressed the
      sustained phosphorylation of Src family kinase after cell detachment, which might
      be independent of phosphorylation of Grb2-binding site. It was indicated that the
      Src/Fyn-Cas pathway is modulated as a target of these suppressive effects by
      ShcC. Reciprocal change of ShcC expression and phosphorylation observed in
      malignant neuroblastoma cell lines might be explained by these phosphotyrosine
      dependent and -independent functions of ShcC.

PMID- 15735677
TI  - Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of
      histone H3 on serine 10 and 28.
AB  - The Ras-mitogen activated protein kinase (Ras-MAPK) pathway plays an integral
      role in the formation of human malignancies. Stimulation of this pathway results
      in phosphorylation of histone H3 at serines 10 and 28 and expression of immediate
      early genes. Phosphorylated (serine 10) H3, which is also acetylated on lysine
      14, is associated with immediate-early genes. In this report, we investigated the
      relationship between these two H3 phosphorylation events in parental and ras
      transformed fibroblasts. Immunoblot analyses of two-dimensional gel patterns
      demonstrated that all three H3 variants were phosphorylated after stimulation of
      the Ras-MAPK pathway and during mitosis. Following stimulation of the Ras-MAPK
      pathway, H3 phosphorylated on serines 10 and 28 was excluded from regions of
      highly condensed chromatin and was present in increased levels in ras-transformed
      cells. Although H3 phosphorylated at serine 10 or 28 was dynamically acetylated,
      H3 phosphorylated at serine 28 had a higher steady state of acetylation than that
      of H3 phosphorylated at serine 10. When visualized with indirect
      immunofluorescence, most foci of phosphorylated serine 28 H3 did not co-localize
      with foci of H3 phosphorylated on serine 10 or phosphoacetylated on serine 10 and
      lysine 14, suggesting that these two phosphorylation events act separately to
      promote gene expression.

PMID- 15735676
TI  - Molecular characterization of PS-341 (bortezomib) resistance: implications for
      overcoming resistance using lysophosphatidic acid acyltransferase (LPAAT)-beta
      inhibitors.
AB  - PS-341 (bortezomib, Velcadetrade mark) is a promising novel agent for treatment
      of advanced multiple myeloma (MM); however, 65% of patients with relapsed
      refractory disease in a phase II study do not respond to PS-341. We have
      previously shown that lysophosphatidic acid acyltransferase (LPAAT)-beta
      inhibitor CT-32615 triggers caspase-dependent apoptosis, and can overcome
      resistance to conventional therapeutics (i.e., dexamethasone, doxorubicin,
      melphalan) in MM cells. In this study, we therefore determined whether CT-32615
      could also overcome resistance to PS-341. We first characterized molecular
      mechanisms of resistance to PS-341 in DHL-4 cells. DHL-4 cells express low levels
      of caspase-3 and caspase-8; furthermore, no cleavage in caspase-8, caspase-9,
      caspase-3, poly ADP-ribose polymerase (PARP), or DNA fragmentation factor 45 was
      triggered by PS-341 treatment. We have previously shown that PS-341 treatment
      triggers phosphorylation of c-Jun NH(2)-terminal kinase (JNK), which subsequently
      induces caspase-dependent apoptosis; conversely, JNK inhibition blocks PS-341
      induced apoptosis. We here show that phosphorylation of SEK-1, JNK, and c-Jun are
      not induced by PS-341 treatment, suggesting that PS-341 does not trigger a stress
      response in DHL-4 cells. Importantly, CT-32615 inhibits growth of DHL-4 cells in
      a time- and dose-dependent fashion: a transient G2/M cell cycle arrest induced by
      CT-32615 is mediated via downregulation of cdc25c and cdc2. CT-32615 triggered
      swelling and lysis of DHL-4 cells, without caspase/PARP cleavage or TUNEL
      positivity, suggesting a necrotic response. Our studies therefore demonstrate
      that LPAAT-beta inhibitor CT-32615 triggers necrosis, even in PS-341-resistant
      DHL-4 cells, providing the framework for its evaluation to overcome clinical PS
      341 resistance and improve patient outcome.

PMID- 15735678
TI  - Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor
      gene lgl, contributes to progression of colorectal cancer.
AB  - The human gene, human giant larvae (Hugl-1/Llg1/Lgl1) has significant homology to
      the Drosophila tumour suppressor gene lethal(2)giant larvae (lgl). The lgl gene
      codes for a cortical cytoskeleton protein, Lgl, that binds Myosin II and is
      involved in maintaining cell polarity and epithelial integrity. The human
      protein, Hugl-1 contains several conserved functional domains found in Lgl,
      suggesting that these proteins may have closely related functions. Whether loss
      of Hugl expression plays a role in human tumorigenesis has so far not been
      extensively investigated. Thus, we evaluated tumour tissues from 94 patients
      undergoing surgery for colorectal cancer (CRC) for loss of Hugl-1 transcription
      and compared our findings with the clinical data from each of these patients. We
      found that Hugl-1 was lost in 75% of tumour samples and these losses were
      associated with advanced stage and particularly with lymph node metastases.
      Reduced Hugl-1 expression during the adenoma-carcinoma sequence occurring as
      early as in colorectal adenomas was detected by both immunohistochemical and
      reverse transcription-polymerase chain reaction analysis. Functional assays with
      ecdysone-inducible cell lines revealed that Hugl-1 expression increased cell
      adhesion and decreased cell migration. Our studies thus indicate that
      downregulation of Hugl-1 contributes to CRC progression.

PMID- 15735679
TI  - Morphological and transcriptional responses of untransformed intestinal
      epithelial cells to an oncogenic beta-catenin protein.
AB  - Aberrant transactivation of a certain set of target genes by the beta-catenin and
      T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor complexes
      has been implicated in the process of intestinal epithelial cells entering early
      colorectal carcinogenesis. A rat intestinal epithelial cell line IEC6 became
      elongated, extended protrusions at cell periphery, and increased stress fibers
      and focal contacts upon the induction of beta-catenin protein stabilized by
      deletion of the N-terminal glycogen synthase kinase-3beta (GSKbeta)
      phosphorylation sites (beta-catenin DeltaN89). We used the GeneChiptrade mark
      oligonucleotide microarray system to examine approximately 24 000 genes and
      identified 13 genes whose expression was altered during the course of this
      morphological transformation. Those genes included known negative regulators of
      the Wnt signaling pathway, Sfrp4 and Axin2; extracellular matrix and related
      molecule, Hxb and Crtl1; cell adhesion and cytoskeletal proteins, Podxl, Igaf4,
      and Itab6; and molecules involved in the insulin and insulin-like growth factor
      (IGF) signaling pathways, Enpp1, Igfbp2, and Sgk. We report the finding that
      insulin-like growth factor-binding protein-2 (IGFBP2) is a direct target gene of
      the beta-catenin and TCF/LEF complexes. The IGFBP2 protein interacts with
      integrins. Disruption of the multigene network system regulating cell adhesion
      and cytoskeleton may be crucial in the initiation of colorectal carcinogenesis.

PMID- 15735680
TI  - The oncogene PDGF-B provides a key switch from cell death to survival induced by
      TNF.
AB  - Tumor necrosis factor (TNF) induces both cell death and survival signals. NF
      kappaB, a transcription factor activated by TNF, is critical for controlling
      survival signals through trans-activation of downstream target genes. However,
      few NF-kappaB target survival genes have been identified with direct roles in
      oncogenesis. We report that platelet-derived growth factor B (PDGF-B), an
      oncogene and growth factor, is highly induced by TNF in fibroblasts in an NF
      kappaB-dependent manner. PDGF-B can rescue NF-kappaB-deficient fibroblasts from
      TNF-mediated killing, and inhibition of PDGF-B signaling sensitizes wild-type
      cells to TNF-induced death. Interestingly, PDGF-B-transformed NIH-3T3 cells are
      even more highly sensitized to TNF-induced cell death with PDGF-B inhibition. Our
      results suggest that while normal cells contain multiple TNF-induced survival
      signals, tumor cells may favor a specific survival gene that is abnormally
      upregulated in order to evade death signals.

PMID- 15735681
TI  - Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated
      mouse zygotes.
AB  - Cell cycle arrest in response to DNA damage is important for the maintenance of
      genomic integrity in higher eukaryotes. We have previously reported the novel p53
      dependent S-phase checkpoint operating in mouse zygotes fertilized with
      irradiated sperm. In the present study, we analysed the detail of the p53
      function required for this S-phase checkpoint in mouse zygotes. The results
      indicate that ATM kinase is likely to be indispensable for the p53-dependent S
      phase checkpoint since the suppression was abrogated by inhibitors such as
      caffeine and wortmannin. However, ATM phosphorylation site mutant proteins were
      still capable of suppressing DNA synthesis when microinjected into sperm
      irradiated zygotes lacking the functional p53, suggesting that the target of the
      phosphorylation is not p53. In addition, the suppression was not affected by
      alpha-amanitin, and p53 protein mutated at the transcriptional activation domain
      was also functional in the suppression of DNA synthesis. However, p53 proteins
      mutated at the DNA-binding domain were devoid of the suppressing activity. Taken
      together, the transcription-independent function of p53 associated with the DNA
      binding domain is involved in the S-phase checkpoint in collaboration with yet
      another unidentified target protein(s).

PMID- 15735682
TI  - HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional
      complex that regulates Src-dependent hypoxia-induced expression of VEGF in
      pancreatic and prostate carcinomas.
AB  - Hypoxia stimulates a number of pathways critical to cancer cell survival,
      including the activation of vascular endothelial growth factor (VEGF)
      transcription. In normal fibroblasts, hypoxia-induced activation of the protein
      tyrosine kinase, Src, is required for VEGF expression. We show here in both
      pancreatic and prostate carcinoma cell lines cobalt chloride (used to mimic
      hypoxia) -induced VEGF expression requires Src activation and leads to increased
      steady-state levels of HIF-1alpha and increased phosphorylation of signal and
      transducer of transcription 3 (STAT3). STAT3 and hypoxia-inducible factor (HIF)
      1alpha bind simultaneously to the VEGF promoter, where they form a molecular
      complex with the transcription coactivators CBP/p300 and Ref-1/APE. Expression of
      activated Src from an inducible promoter is sufficient to increase VEGF
      expression and form these STAT3/HIF-1alpha-containing promoter complexes.
      Inhibition of DNA binding by expression of either STAT3 or HIF-1alpha dominant
      negative mutants significantly reduces VEGF expression. These data suggest that
      the binding of both STAT3 and HIF-1alpha to the VEGF promoter is required for
      maximum transcription of VEGF mRNA following hypoxia.

PMID- 15735683
TI  - p53 mediates a default programme of mammary gland involution in the absence of
      STAT3.
AB  - Previous studies have demonstrated a proapoptotic role for the transcription
      factor STAT3 in involuting murine mammary epithelium, resulting in delayed
      involution and lower levels of apoptosis in the STAT3 null gland relative to wild
      type controls. As p53 was implicated in the eventual involution of the STAT3 null
      gland, we examined the effect of STAT3 loss in the mammary gland in a p53 null
      background. Combined loss of STAT3 and p53 severely perturbed involution, with
      hyperdelayed loss of epithelium and reappearance of adipocytes. The early
      apoptotic response was almost completely abrogated, although elevated levels of
      delayed apoptosis persisted at days 6, 17 and 4 weeks of involution in STAT3-p53
      doubly null mammary glands. A 5.7-fold upregulation of the cyclin-dependent
      kinase inhibitor p21Waf1 at 3 days of involution in STAT3 null glands was
      abolished in STAT3-p53 doubly null glands -- suggesting that the critical factor
      triggering delayed involution in the STAT3 null gland is a p53-dependent rise in
      p21Waf1 levels around day 3 of involution. Further, STAT3-p53 doubly null glands
      showed significantly higher levels of proliferation compared to STAT3 or p53
      singly null (or wild-type) glands at days 6, 17 and 4 weeks of involution.
      Combined loss of STAT3 and p53 therefore results in hyperdelayed involution,
      demonstrating their synergistic physiological roles in normal involution. This
      inappropriate retention of p53-deficient cells may represent a novel mechanism of
      tumour predisposition.

PMID- 15735684
TI  - Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells
      containing downstream mutations.
AB  - Aberrant Wnt signaling, mainly through mutations of APC and in some cases of
      CTNNB1 or AXIN2, has been found in the majority of colorectal cancers. Recently,
      frequent promoter hypermethylation was identified to cause silencing of the
      secreted frizzled-related protein (sFRP) family in colorectal cancer. Restoration
      of sFRP in colorectal cancer cells attenuates Wnt signaling even in the presence
      of downstream mutations. Here we show that Wnt inhibitory factor-1 (WIF-1), a
      different secreted antagonist of Wnt signaling, is also silenced by promoter
      hypermethylation in colorectal cancer cells. Restoration of WIF-1 function, Wnt-1
      siRNA, or a monoclonal anti-Wnt-1 antibody that we developed attenuates Wnt-1
      signaling and induces significant apoptosis in these cells containing downstream
      mutations and expressing Wnt-1. In addition, this monoclonal anti-Wnt-1 antibody
      showed synergistic effects with docetaxel in treating these colorectal cancer
      cells and great efficacy in treating primary colorectal cancer cultures freshly
      prepared from patients. Therefore, our data support the hypothesis that
      constitutive Wnt signaling may be required to complement downstream mutations in
      the evolution of colorectal cancer. Furthermore, our results suggest that
      blockade of the Wnt signal may have a therapeutic role in the treatment of
      colorectal cancer.

PMID- 15735685
TI  - The rat tyrosine phosphatase eta increases cell adhesion by activating c-Src
      through dephosphorylation of its inhibitory phosphotyrosine residue.
AB  - The expression of the receptor protein tyrosine phosphatase r-PTPeta is
      drastically reduced in rat and human malignant thyroid cells, whereas its
      restoration reverts the neoplastic phenotype of retrovirally transformed rat
      thyroid cells. Moreover, reduced levels and loss of heterozygosity of DEP-1, the
      human homolog of r-PTPeta, have been found in many human neoplasias. Here, we
      report that the r-PTPeta protein binds to c-Src in living cells and
      dephosphorylates the c-Src inhibitory tyrosine phosphorylation site (Tyr 529),
      thereby increasing c-Src tyrosine kinase activity in malignant rat thyroid cells
      stably transfected with r-PTPeta. Tyrosine phosphorylation of focal adhesion
      kinase (FAK) and paxillin was enhanced in r-PTPeta-expressing cells. This was
      associated with increased adhesion of malignant r-PTPeta-transfected thyroid
      cells vs both untransfected cells and cells stably transfected with an inactive r
      PTPeta mutant. Treatment of rat thyroid cells with the c-Src inhibitor PP2
      decreased cell adhesion to a higher extent in r-PTPeta-transfected cells than in
      mock-transfected or stably transfected cells with the inactive r-PTPeta mutant,
      indicating that r-PTPeta regulates cell-substratum adhesion by activating c-Src.
      Interestingly, the extent of both c-Src dephosphorylation at Tyr 529, FAK and
      paxillin phosphorylation, and the increased cell adhesion were associated with
      the degree of r-PTPeta expression.

PMID- 15735686
TI  - Growth suppression induced by the TRC8 hereditary kidney cancer gene is dependent
      upon JAB1/CSN5.
AB  - TRC8 encodes an E3-ubiquitin ligase disrupted in a family with hereditary renal
      cell carcinoma (RCC). We previously reported that Drosophila Trc8 (DTrc8)
      overexpression inhibits growth and that human and fly proteins interact with with
      the COP9 signalosome (CSN) subunit JAB1/CSN5. However, further mechanistic
      evidence linking DTrc8 growth suppression to CSN5 was lacking. Here, we show that
      haploinsufficiency of CSN5, or a T100I point mutation (CSN5(3)), relieved growth
      suppression by DTrc8, whereas CSN5(1) (E160V) and CSN5(2) (G147D) mutations had
      no effect. The strength of yeast two-hybrid interactions between DTrc8 and CSN5
      were in complete agreement with the observed phenotypes. DTrc8 overexpression
      resulted in elevated levels of CSN5 and CSN7, but had no effect on NEDD8-modified
      Cul-1. In contrast to CSN5, heterozygosity for CSN4null had no effect on the
      DTrc8 phenotype. We also looked for genetic interactions between DTrc8 and other
      MPN domain proteins in the CSN and 26S proteasome lid. CSN6 haploinsufficiency
      restored growth, whereas reduction of proteasome subunits RPN8 or RPN11 had no
      effect. DTrc8 expression increased the level of digitonin-extractable CSN
      complex, consistent with elevated levels of CSN5 and 7. Our genetic results
      confirm that DTrc8-induced growth suppression is CSN5 (and CSN6) dependent. While
      there was no obvious influence on CSN deneddylation activity, the increase in CSN
      subunits and holocomplex suggests that TRC8 modulates signalosome levels or
      compartmentalization.

PMID- 15735687
TI  - Combined inhibition of extracellular signal-regulated kinases and HSP90
      sensitizes human colon carcinoma cells to ionizing radiation.
AB  - Indomethacin, a common nonsteroidal anti-inflammatory drug, has been shown to
      enhance radiation-mediated cell-killing effect through the activation of p38
      mitogen-activated protein kinase (MAPK). We found that indomethacin strongly
      reduced the basal level of extracellular signal-regulated kinases 1 and 2
      (ERK1/2) in HT-29 human colon carcinoma cells. The inhibition of ERK1/2 by
      indomethacin was only observed in cells with high basal activities of ERK1/2 such
      as HT-29 cells, but not in cells with low basal activities, such as HeLa. Cell
      cycle analysis of HT-29 cells exposed with indomethacin showed a partial G1/S
      arrest and slow DNA synthesis. However, the treatment with NS398, a specific COX
      1/2 inhibitor, failed to show any effect on cell cycle, indicating that the
      inhibition of COX-1/2 is not responsible for cell cycle arrest. Since U0126, a
      specific inhibitor for MEK1/2, also induced a partial G1/S arrest, the G1/S
      arrest induced by indomethacin is, at least in part, caused by the inhibition of
      ERK1/2. Cell proliferation of HT-29 was inhibited by the treatment of U0126 but
      not in HeLa cells, and the treatment of HT-29 cells with U0126 enhanced radiation
      sensitivity possibly due to the accumulation of cells in G1 phase. We found that
      17-allylamino-17-demethoxygeldanamycin, a geldanamycin delivative,
      radiosensitized HT-29 cells at a relatively low dose of irradiation, and
      indomethacin and U0126 further enhanced this effect. Therefore, tumor cells with
      elevated ERK1/2 activity can be effectively sensitized to radiation treatment by
      a combinational inhibition of HSP90 and MAPK activity.

PMID- 15735688
TI  - IL-2- and STAT5-regulated cytokine gene expression in cells expressing the Tax
      protein of HTLV-1.
AB  - Interleukin-2 (IL-2) mediates cell cycle progression and antiapoptosis in human T
      cells via several signal transduction pathways. The Tax protein of the human T
      cell leukemia virus type I (HTLV-1) deregulates cell growth and alters the role
      of IL-2 in infected cells. However, Tax-immortalized cells stay dependent on IL
      2, suggesting that events besides HTLV-1 gene expression are required for
      leukemia to develop. Here, IL-2-dependent and -independent events were analysed
      in a human T cell line immortalized by Tax. These studies show that, of the
      signaling pathways evaluated, only STAT5 remains dependent. Microarray analyses
      revealed several genes, including il-5, il-9 and il-13, are uniquely upregulated
      by IL-2 in the presence of Tax. Bioinformatics and supporting molecular biology
      show that some of these genes are STAT5 targets, explaining their IL-2
      upregulation. These results suggest that IL-2 and viral proteins work together to
      induce gene expression, promoting the hypothesis that deregulation via the
      constitutive activation of STAT5 may lead to the IL-2-independent phenotype of
      HTLV-1-transformed cells.

PMID- 15735689
TI  - Aneurysmal bone cyst variant translocations upregulate USP6 transcription by
      promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes.
AB  - Aneurysmal bone cysts (ABC) are locally aggressive bone tumors that often feature
      chromosome 17p13 rearrangements. One of the ABC 17p13 rearrangements-
      t(16;17)(q22;p13)--was recently shown to create a CDH11-USP6 fusion in which the
      USP6/TRE17 oncogene is overexpressed through juxtaposition with the CDH11
      promoter. Herein, we characterize four different ABC translocations involving
      17p13, and we show that each is associated with a novel USP6 fusion oncogene.
      Specifically, we demonstrate that t(1;17), t(3;17), t(9;17), and t(17;17) result
      in USP6 fusions with TRAP150 (thyroid receptor-associated protein 150), ZNF9
      (ZiNc Finger 9), Osteomodulin, and COL1A1 (Collagen 1A1), respectively. The
      oncogenic mechanism in these fusion genes is akin to CDH11-USP6, with the USP6
      coding sequences juxtaposed to the promoter regions in each of the four novel
      translocation partners. The novel fusion partners appear well suited to drive
      USP6 transcription in the bone/mesenchymal context: osteomodulin is expressed
      strongly in osteoblastic lineages, and the COL1A1 promoter has an oncogenic role
      in the mesenchymal cancer dermatofibrosarcoma protuberans. In summary, these
      studies show that USP6 oncogenic activation results from heterogeneous genomic
      mechanisms involving USP6 transcriptional upregulation by juxtaposition with
      ectopic promoters.

PMID- 15735690
TI  - SLUG in cancer development.
AB  - The SNAIL-related zinc-finger transcription factor, SLUG (SNAI2), is critical for
      the normal development of neural crest-derived cells and loss-of-function SLUG
      mutations have been proven to contribute to piebaldism and Waardenburg syndrome
      type 2 in a dose-dependent fashion. While aberrant induction of SLUG has been
      documented in cancer cells, relatively little is known about the consequences of
      SLUG overexpression in malignancy. To investigate the potential role of SLUG
      overexpression in development and in cancer, we generated mice carrying a
      tetracycline-repressible Slug transgene. These mice were morphologically normal
      at birth, and developed mesenchymal tumours (leukaemia and sarcomas) in almost
      all cases examined. Suppression of the Slug transgene did not rescue the
      malignant phenotype. Furthermore, the BCR-ABL oncogene, which induces Slug
      expression in leukaemic cells, did not induce leukaemia in Slug-deficient mice,
      implicating Slug in BCR-ABL leukaemogenesis in vivo. Overall, the findings
      indicate that while Slug overexpression is not sufficient to cause overt
      morphogenetic defects in mice, they demonstrate a specific and critical role for
      Slug in the pathogenesis of mesenchymal tumours.

PMID- 15735691
TI  - Y-box-binding protein 1 confers EGF independence to human mammary epithelial
      cells.
AB  - The epidermal growth factor receptor (EGFR) is linked to poor outcome in breast
      cancer, and resistance to hormonal therapy is often accompanied by activation of
      growth factor receptors. To investigate the mechanism(s) by which EGFR becomes
      activated in breast cancer, we screened a cDNA expression library for genes that
      mediate EGF-independent proliferation of human mammary epithelial cells (HMECs).
      We isolated the NSEP1 cDNA encoding Y-box-binding protein 1 (YB-1), a
      multifunctional transcriptional and translational regulator. This cDNA conferred
      growth factor independence to HMECs. YB-1-transduced cells overexpressed EGFR,
      but ErbB-2 (Her-2/neu) levels were unchanged. Moreover, EGFR was constitutively
      phosphorylated in the absence of exogenous ligand. In these cells, an EGFR
      blocking antibody failed to inhibit proliferation, conditioned medium activity
      could not be detected, and the synthesis of EGFR ligands was reduced compared to
      parental cells. This suggests that EGFR is activated in a ligand-independent
      fashion. However, cell growth could be blocked with an ErbB kinase inhibitor,
      indicating that EGFR signaling plays a major role in YB-1-induced growth factor
      independence. Taken together, our results demonstrate that YB-1 overexpression
      can induce EGF independence in HMECs via activation of the EGFR pathway. This
      could represent one of the mechanisms by which YB-1 contributes to breast tumor
      aggressiveness.

PMID- 15735692
TI  - The guanine nucleotide exchange factor Tiam1 increases colon carcinoma growth at
      metastatic sites in an orthotopic nude mouse model.
AB  - Alterations in migration and adhesion are critical to invasion and metastasis. To
      examine signaling pathways important for colon tumor metastasis, cells of
      increased migratory potential from the low migratory SW480 human colorectal
      carcinoma parental cell line were biologically selected by serial migration
      through modified Boyden chambers. Several sublines were obtained with
      statistically significantly increased migration relative to the parental cell
      line. One highly migratory population was single-cell cloned and characterized.
      The migratory clones exhibit a four- to five-fold increase in protein and mRNA
      expression of T-lymphoma invasion and metastasis gene 1 (Tiam1), a guanine
      nucleotide exchange factor. To determine directly the role of Tiam1 in the
      migration of these migratory sublines, the parental SW480 cell line was
      transfected with a plasmid encoding the Tiam1 protein, and single cell clones
      were established. Ectopic expression of Tiam1 in these clones led to morphologic
      changes identical to biologically selected clones and increased migration.
      Finally, the implantation of clones that overexpress Tiam1 into the cecum of
      athymic mice resulted in tumor growth in the spleen, liver, and lung, whereas
      parental cells do not form tumors by this route of injection. These results
      demonstrate that overexpression of Tiam1 contributes to the metastatic phenotype
      of colon cancer cells.

PMID- 15735693
TI  - Upregulation of PKC-delta contributes to antiestrogen resistance in mammary tumor
      cells.
AB  - Acquired resistance to tamoxifen (Tam) in breast cancer patients is a serious
      therapeutic problem. We have previously reported that protein kinase C-delta (PKC
      delta) plays a major role in estrogen (E2)-mediated cell proliferation. To
      determine if PKC-delta is one of the major alternate signaling pathways that
      supports cell growth in the presence of Tam, we determined the levels of PKC
      isoforms in four different models of antiestrogen-resistant cells. Three out of
      four antiestrogen resistance cell lines (Tam/MCF-7, ICI/MCF-7 and HER-2/MCF-7)
      expressed significantly high levels of both total and activated PKC-delta levels
      compared to sensitive cells. Estrogen receptor (ER) alpha content and function
      are maintained in all the antiestrogen-resistant cell lines. Overexpressing
      active PKC-delta in Tam-sensitive MCF-7 cells (PKC-delta/MCF-7) led to Tam
      resistance both in vitro and in vivo. Inhibition of PKC-delta by rottlerin (a
      relatively specific inhibitor of PKC-delta) or siRNA significantly inhibited
      estrogen- and Tam-induced growth in antiestrogen-resistant cells. PKC-delta
      levels are significantly higher in Tam-resistant tumors compared to Tam-sensitive
      tumors in xenograft model (P<0.05). Taken together, these data suggest that PKC
      delta plays a major role in antiestrogen resistance in breast tumor cells and
      thus provides a new target for treatment.

PMID- 15735694
TI  - Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed
      growth hormone/prolactin cell pituitary adenomas and natural killer cell
      lymphomas.
AB  - Overexpression of HMGA1 proteins is a constant feature of human carcinomas.
      Moreover, rearrangements of this gene have been detected in several human benign
      tumors of mesenchymal origin. To define the role of these proteins in cell
      transformation in vivo, we have generated transgenic mice overexpressing
      ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/prolactin
      cell pituitary adenomas and natural killer (NK)-T/NK cell lymphomas. The HMGA1
      induced expression of IL-2 and IL-15 proteins and their receptors may account for
      the onset of these lymphomas. At odds with mice overexpressing a wild-type or a
      truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet cell
      hyperplasia frequently occurred and no increase in body size and weight was
      observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of
      the HMGA1 gene also in vivo.

PMID- 15735695
TI  - Bcr-Abl-mediated suppression of normal hematopoiesis in leukemia.
AB  - A variety of experimental evidence including findings in various mouse models
      indicates that the BCR-ABL oncogene is the cause of chronic myeloid leukemia
      (CML). Since normal hematopoietic cells in marrow and spleen are replaced with
      proliferating leukemic blasts, we determined whether this is an active process
      mediated by the leukemia cells. The lipocalin 24p3 was reported to be secreted by
      mouse hematopoietic cells deprived of IL-3, resulting in apoptosis induction in a
      variety of hematopoietic cells including bone marrow cells. Here, we show that
      BCR-ABL+ mouse hematopoietic cells induced persistent expression and secretion of
      24p3. Importantly, BCR-ABL+ hematopoietic cells were resistant to the apoptotic
      effects of 24p3. The expression of the Bcr-Abl oncoprotein and its tyrosine
      kinase were required for induction of 24p3 expression. Co-culture studies showed
      that BCR-ABL+ cells induced apoptosis in BCR-ABL negative cells. Antisense
      24p3/siRNA expression reduced the level of 24p3 protein in both BCR-ABL+ cells
      and in conditioned medium (CM) obtained from these cells. CM from BCR-ABL+ cells
      expressing antisense 24p3/siRNA had reduced apoptotic activity for target cells;
      24p3 antibody also reduced the apoptotic activity of the CM. Leukemic mice
      induced by BCR-ABL+ cells expressing either antisense 24p3 or 24p3 siRNA had
      increased levels of normal hematopoiesis and reduced invasion of leukemia cells
      in marrow and spleen tissues. These findings indicate that suppression of normal
      hematopoiesis in BCR-ABL-induced leukemia is an active process involving
      secretion of the cell death-inducing factor 24p3 by mouse leukemia cells, raising
      the possibility that similar factors are involved in BCR-ABL+ CML.

PMID- 15735696
TI  - Molecular signature of retinoic acid treatment in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid
      leukemia characterized by a block of differentiation at the promyelocytic stage.
      APL patients respond to pharmacological concentrations of all-trans retinoic acid
      (RA) and disease remission correlates with terminal differentiation of leukemic
      blasts. The PML/RAR oncogenic transcription factor is responsible for both the
      pathogenesis of APL and for its sensitivity to RA. In order to identify
      physiological targets of RA therapy, we analysed gene expression profiles of RA
      treated APL blasts and found 1056 common target genes. Comparing these results to
      those obtained in RA-treated U937 cell lines revealed that transcriptional
      response to RA is largely dependent on the expression of PML/RAR. Several genes
      involved in the control of differentiation and stem cell renewal are early
      targets of RA regulation, and may be important effectors of RA response.
      Modulation of chromatin modifying genes was also observed, suggesting that
      specific structural changes in local chromatin domains may be required to promote
      RA-mediated differentiation. Computational analysis of upstream genomic regions
      in RA target genes revealed nonrandom distribution of transcription factor
      binding sites, indicating that specific transcriptional regulatory complexes may
      be involved in determining RA response.

PMID- 15735697
TI  - Ubiquitin-proteasome degradation of KLF5 transcription factor in cancer and
      untransformed epithelial cells.
AB  - Ubiquitin-mediated proteolysis plays a central role in controlling intracellular
      levels of essential regulatory molecules such as p53, cyclins, myc, BRCA1, HIF
      1alpha, etc. The Kruppel-like factor 5 (KLF5) transcription factor regulates
      biological processes involved in carcinogenesis, angiogenesis, and smooth muscle
      cell differentiation. In carcinogenesis, KLF5's role has been indicated by
      frequent genetic deletion as well as functional studies. Here we show that KLF5
      is an unstable protein with a short half-life. Destruction of KLF5 was prevented
      by each of the proteasome-specific inhibitors tested but not by an inhibitor for
      trypsin-like proteases and cysteine proteases or by a lysosome inhibitor in
      epithelial cells. Furthermore, KLF5 underwent ubiquitination, and deletion of a
      56-amino-acid sequence adjacent to a known transactivation domain of KLF5
      significantly reduced its ubiquitination and degradation. Interestingly, cancer
      cells appeared to be more active in KLF5 degradation than untransformed
      epithelial cells, yet their proteasome activity was not higher. These results
      suggest that KLF5 protein is degraded at least in part through ubiquitination
      proteasome pathway, which may have become hyperactive for KLF5 in cancer cells.

PMID- 15735698
TI  - ECop (EGFR-coamplified and overexpressed protein), a novel protein, regulates NF
      kappaB transcriptional activity and associated apoptotic response in an
      IkappaBalpha-dependent manner.
AB  - In the present study, we describe the function of a novel protein, ECop (EGFR
      Coamplified and overexpressed protein), in the regulation of NF-kappaB activity.
      Ectopic expression of ECop increases NF-kappaB transcriptional activity by
      promoting nuclear translocation and DNA binding of NF-kappaB, and ECop-induced NF
      kappaB activation confers cellular resistance to apoptotic challenge. In ECop
      knockdown cells, NF-kappaB transcriptional activity is suppressed due to delayed
      IkappaBalpha degradation, which results in a delayed nuclear translocation as
      well as decreased DNA binding of NF-kappaB. Suppression of NF-kappaB activation
      by ECop knockdown increases cellular susceptibility to apoptosis. These results
      suggest that ECop is a key regulator of NF-kappaB signaling, and that high-level,
      amplification-mediated ECop expression, such as that occurring in tumors with
      amplified EGFR, could contribute to resistance to apoptosis.

PMID- 15735699
TI  - Increased expression of the major heat shock protein Hsp72 in human prostate
      carcinoma cells is dispensable for their viability but confers resistance to a
      variety of anticancer agents.
AB  - The major heat shock protein Hsp72 is expressed at high levels in various types
      of cancer. Here we attempt to clarify the role of Hsp72 in prostate cancer cells
      by studying the effects of specific downregulation of this protein using siRNA
      and antisense RNA approaches. Contrary to previous reports, specific depletion of
      Hsp72 did not reduce viability of the prostate carcinoma cell lines PC-3 and DU
      145. However, even short-term downregulation of Hsp72 in these cells made them
      more sensitive to hyperthermia, inhibitors of proteasome and Hsp90, and tumor
      necrosis factor. Interestingly, prolonged downregulation of Hsp72 in PC-3 cells
      over 3 weeks aggravated these effects, as well as enhanced the sensitivity of
      cells to oxidative stress, radiation, cis-platinum, vinblastin and taxol. The
      increased sensitivity to the anticancer agents was due to increased apoptosis, as
      well as other types of cell death, which resulted in the loss of clonogenic
      survival. Prolonged downregulation of Hsp72 led to severe suppression of the
      major survival pathways, ERK and NF-kappaB, which may be responsible for enhanced
      sensitivity of prostate carcinoma cells to a variety of anticancer treatments, as
      well as reduction of the cell's capability of forming colonies in soft agar.

PMID- 15735700
TI  - Signalling pathways leading to neuroblastoma differentiation after serum
      withdrawal: HDL blocks neuroblastoma differentiation by inhibition of EGFR.
AB  - Neuroblastoma is the second most common pediatric malignancy, characterized by a
      high rate of unexplained spontaneous remissions. Much progress has been made in
      understanding neuroblastoma differentiation triggered by certain agents such as
      retinoic acid. However, little is known about the signalling pathways that lead
      to differentiation of neuroblastoma cells due to serum withdrawal. We found that
      in Neuro2a neuroblastoma cells, EGFR, ERK1/2 and Akt showed increased
      phosphorylation after serum withdrawal, and that the activation of EGFR was
      necessary for the activation of Akt and ERK1/2. Inhibition of EGFR, ERK1/2 and
      PI3K blocked neuroblastoma differentiation after serum withdrawal. Interestingly,
      addition of high-density lipoprotein (HDL) abrogated serum-withdrawal induced
      neuroblastoma differentiation, as well as the activation of EGFR. Our results
      demonstrate a novel role for serum-derived lipoproteins in the control of
      receptor tyrosine kinase activity.

PMID- 15735701
TI  - Caspase-9 can antagonize p53-induced apoptosis by generating a p76(Rb) truncated
      form of Rb.
AB  - The tumor suppressor Rb (retinoblastoma protein) is known to regulate p53
      dependent apoptosis, but the mechanisms involved are unclear. In a rat fibroblast
      model, we previously observed that caspase inhibition potentiates p53-dependent
      apoptosis and prevents the Rb cleavage associated with p53 activation. These
      results suggested that a caspase(s) can antagonize p53-mediated apoptosis via the
      production of a protective Rb truncated form. Here, we identify caspase-9 as the
      caspase that interferes, upstream of the mitochondrion, with p53-induced
      apoptosis in both immortalized and primary fibroblasts. This caspase can be
      detected as a p38 processed form in living cells, in the absence of apoptosome
      formation and apoptotic signal. We also provide evidence that the involvement of
      caspase-9 in a pre-mitochondrial protective pathway results from the previously
      undescribed cleavage of Rb, at a LExD site, into a p76(Rb) form, which
      antagonizes p53-induced apoptosis. These results establish that a truncated form
      of Rb can display an antiapoptotic activity, rather than just being a by-product
      of Rb degradation.

PMID- 15735702
TI  - BRCA1-mediated G2/M cell cycle arrest requires ERK1/2 kinase activation.
AB  - Germline mutations in the BRCA1 gene are associated with an increased
      susceptibility to the development of breast and ovarian cancers. Evidence
      suggests that BRCA1 protein plays a key role in mediating DNA damage-induced
      checkpoint responses. Several studies have shown that ectopic expression of BRCA1
      in human cells can trigger cellular responses similar to those induced by DNA
      damage, including G2/M cell cycle arrest and apoptosis. While the effects of
      ectopic BRCA1 expression on the G2/M transition and apoptosis have been
      extensively studied, the factors that dictate the balance between these two
      responses remain poorly understood. We have recently shown that ectopic
      expression of BRCA1 in MCF-7 human breast cancer cells resulted in activation of
      extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and G2/M cell
      cycle arrest. Furthermore, inhibition of BRCA1-induced ERK1/2 activation using
      mitogen-activated protein kinase kinase 1 and 2 (MEK1/2)-specific inhibitors
      resulted in increased apoptosis, suggesting a potential role of ERK1/2 kinases in
      BRCA1-mediated G2/M checkpoint response. In this study, we assessed the role of
      ERK1/2 kinases in the regulation of BRCA1-mediated G2/M cell cycle arrest.
      Results indicate that BRCA1-induced G2/M cell cycle arrest and ERK1/2 activation
      correlate with changes in the level and/or activity of several key regulators of
      the G2/M checkpoint, including activation of Chk1 and Wee1 kinases, induction of
      14-3-3, and down-regulation of Cdc25C. Furthermore, inhibition of ERK1/2 kinases
      using MEK1/2-specific inhibitors results in a marked attenuation of the BRCA1
      induced G2/M arrest. Biochemical studies established that ERK1/2 inhibition
      abolished the effects of BRCA1 on components of the G2/M checkpoint, including
      regulation of Cdc25C expression and activation of Wee1 and Chk1 kinases. These
      results implicate a critical role of ERK1/2 signaling in the regulation of BRCA1
      function on controlling the G2/M checkpoint responses.

PMID- 15735703
TI  - Survivin mediates resistance to antiandrogen therapy in prostate cancer.
AB  - Resistance to antiandrogen therapy in patients with metastatic prostate cancer
      poses a major challenge, which, if overcome, may lead to significant advances in
      the treatment of these patients. Hormone resistance of prostate cancer develops,
      in part, from upregulation of antiapoptotic genes after androgen deprivation.
      Given the accumulating evidence that Survivin, a new member of the inhibitor of
      apoptosis (IAP) family, is associated with both cancer progression and drug
      resistance, we hypothesized that Survivin plays a potentially important role in
      hormone therapy resistance, and that targeting of Survivin may enhance
      sensitivity to antiandrogen therapy in prostate cancer. Patterns of Survivin
      expression were assessed in three prostate cancer cell lines LNCaP, PC-3, and DU
      145 using quantitative Western analysis. All three cell lines were found to
      strongly express Survivin. In LNCaP cells with intact androgen receptors (ARs),
      it was observed that androgen stimulation with 5alpha-dihydrotestosterone (DHT)
      increased Survivin expression. Conversely, treatment with Flutamide decreased
      Survivin expression in LNCaP cells. We next studied the functional effect of
      Survivin on sensitivity to Flutamide. LNCaP cells were infected with replication
      deficient adenoviruses encoding either wild-type Survivin pAd-S(WT) or a
      phosphorylation-defective Survivin Thr34 --> Ala dominant-negative mutant pAd
      S(T34A), and then treated with Flutamide. Cell viability and apoptosis were
      assessed in vitro and in vivo. It was determined that Survivin can mediate
      resistance to such antiandrogen therapies based on our assays. Direct androgen
      stimulation resulted in pan-cell cycle expression of Survivin, which was found to
      be mediated by AKT, as it was determined that exogenous insulin-like growth
      factor-1 (IGF-1), a known activator of AKT signaling, could increase Survivin
      expression and result in pan-cell cycle expression even in AR-negative prostate
      cancer cell lines PC-3 and DU-145. Given this alternative mechanism of Survivin
      expression and our findings that Survivin can mediate resistance to Flutamide
      treatment, we further investigated whether IGF-1-mediated activation of Survivin
      via AKT could mediate resistance to antiandrogen therapy. Both in vitro and in
      vivo, this was found to be the case, supporting a novel mechanism of resistance
      to antiandrogen therapy. Our study indicates that upregulation of Survivin via
      IGF-1 signaling confers resistance to Flutamide in prostate cancer cells.
      Targeted inhibition of Survivin appears to enhance the therapeutic effects of
      Flutamide in vitro and in vivo, revealing a novel strategy to enhance sensitivity
      to androgen ablation therapy.

PMID- 15735704
TI  - v-Jun downregulates the alpha 2 (I) collagen target gene indirectly through
      Sp1/3.
AB  - Transformation of chick embryo fibroblasts (CEFs) by the v-Jun oncoprotein
      correlates with a downregulation of the alpha 2 (I) collagen gene. To investigate
      whether this gene constitutes a direct target of v-Jun, an analysis of a large
      proximal fragment of the promoter, extending from position -1080 to +109, was
      performed. Transient transfections with -1080/+109 and deleted derivatives
      revealed that a short proximal fragment, -433/+11, is the target for repression
      by v-Jun. Extensive analysis, conducted in CEFs and in Sp1/3-deficient Drosophila
      SL2 cells, further showed that (i) high constitutive activity of -433/+11
      requires a direct binding of the ubiquitous Sp1 and/or Sp3 transcription factors
      acting on two distinct motifs, that is, a proximal TCC-rich region and an
      upstream GC box, and that (ii) repression by v-Jun does not require any direct
      binding of the oncoprotein to the DNA, but an indirect binding within a v-Jun
      Sp1/3-DNA chromatin-associated complex. This situation is reminiscent of a
      situation previously reported with the tata-less, SPARC (secreted protein,
      acidic, and rich in cysteine) target promoter that regulates the expression of
      another extracellular matrix component in the same model of cell transformation.
      Taken together, these data reinforce the view that, at least in CEFs, v-Jun
      downregulates a family of direct target genes by binding to the DNA indirectly
      through Sp1/3.

PMID- 15735705
TI  - Phosphorylation of MdmX by CDK2/Cdc2(p34) is required for nuclear export of Mdm2.
AB  - Mdm2 and MdmX function as cellular regulators of the p53 tumor suppressor
      protein. Intriguingly, the activities of these proteins are interdependent; MdmX
      stabilizes Mdm2, enabling its activities towards p53, but it also requires Mdm2
      for its nuclear localization. Here we demonstrate that via its phosphorylation by
      CDK2/Cdc2p34, MdmX regulates nuclear export of Mdm2. Cdc2p34 phosphorylates MdmX
      on Ser 96 in vitro. Mutation within this site (MdmX(S96A)) impairs, whereas
      phosphomimic substitution (MdmX(S96D)) increases the cytoplasmic localization of
      MdmX, suggesting that CDK2/Cdc2p34 phosphorylation is required for export of MdmX
      from the nucleus. Consequently, cells that express MdmX(S96A) retain Mdm2 in
      their nuclei, suggesting that export of Mdm2 to the cytoplasm is MdmX-dependent.
      Similarly, treatment of cells with the pharmacological inhibitor of CDK2/Cdc2p34
      or with a dominant-negative Cdc2 results in nuclear localization of MdmX and Mdm2
      and decreases the level of Mdm2 expression. Since Cdc2p34 is active in
      nonstressed conditions, our finding provides a novel insight into the signaling
      cascade involved in the regulation of MdmX localization and for regulation of
      Mdm2 localization and stability.

PMID- 15735706
TI  - Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation.
AB  - The JAK/STAT signalling pathway mediates both antiproliferative responses
      following interferon stimulation and cellular proliferation in response to
      cytokines such as interleukins and growth factors. Central to these responses are
      the seven vertebrate STAT molecules, misregulation of which is implicated in a
      variety of malignancies. We have investigated the proliferative role of the
      single Drosophila STAT92E, part of the evolutionarily conserved JAK/STAT cascade.
      During second instar larval wing disc development pathway activity is both
      necessary and sufficient to promote proliferation of this epithelial cell type.
      However by later stages, endogenous STAT92E is stimulated by a noncannonical
      mechanism to exert pronounced antiproliferative effects. Ectopic canonical
      activation is sufficient to further decrease proliferation and leads to the
      premature arrest of cells in the G2 phase of the cell cycle. The single STAT92E
      present in Drosophila therefore mediates both proproliferative functions
      analogous to vertebrate interleukin-stimulated STAT3 and antiproliferative
      functions analogous to interferon-stimulated STAT1. Pro- and antiproliferative
      roles therefore represent ancestral activities conserved through evolution and
      subsequently assigned to distinct molecules.

PMID- 15735707
TI  - Stepwise occurrence of a complex unbalanced translocation in neuroblastoma
      leading to insertion of a telomere sequence and late chromosome 17q gain.
AB  - In neuroblastoma, the most frequent genetic alterations are unbalanced
      translocations involving chromosome 17. To gain insights into these
      rearrangements, we have characterized a previously identified der(1)t(1;17) of
      the CLB-Bar cell line. The 17q breakpoint was mapped by FISH. Subsequently, a
      rearranged fragment was identified by Southern analysis, cloned in a lambda
      vector and sequenced. The chromosome rearrangement is more complex than expected
      due to the presence of an interstitial 4p telomeric sequence between chromosome
      1p and 17q. Three different genes, which may play a role in neuroblastoma
      development, are disrupted by the translocation breakpoints. Indeed, the 3'UTR of
      the PIP5K2B gene on chromosome 17q is directly fused to the (TTAGGG)n repeat of
      the chromosome 4p telomere, and the (1;4) fusion disrupts the MACF1 (microtubule
      actin crosslinking factor 1) and POLN genes, respectively. Interestingly, the
      (1;4) fusion was present at diagnosis and at relapse, whereas the (4;17) fusion
      was detected at relapse only, leading to a secondary 17q gain confirmed by array
      CGH therefore indicating that 17q gain may not be a primary event in
      neuroblastoma. Finally, screening of a panel of neuroblastoma cell lines
      identified interstitial telomeric sequences in three other cases, suggesting that
      this may be a recurrent mechanism leading to unbalanced translocations in
      neuroblastoma.

PMID- 15735708
TI  - The cancer chemopreventive agent resveratrol induces tensin, a cell-matrix
      adhesion protein with signaling and antitumor activities.
AB  - During a search to identify resveratrol (3,5,4'-trihydroxy-trans-stilbene, RV)
      target genes in the human erythroleukemic K562 cell line, we show here that the
      tensin gene and protein levels are remarkably induced by this dietary polyphenol.
      Tensin, a cell-matrix adhesion protein binding the integrins and cytoskeletal
      actin filaments also interacts with PI3-kinase and JNK signaling pathways. Tensin
      induction by RV is associated with increased K562 cell adhesion to fibronectin,
      cell spreading and actin polymerization. The same responses were observed in the
      tensin-deficient MCF7 human breast cancer cell line. In K562 and MCF7 cells
      treated by RV, tensin was found in punctate and intracytoplasmic areas. In MCF7
      epithelial cells, induction of tensin is not exclusively associated with plasma
      membrane-bound vinculin, suggesting a dual localization of tensin in both focal
      and fibrillar adhesions. Pharmacological blockade of PI3-kinase and Rho
      GTPases/Rho-kinase resulted in selective depletion of focal adhesions,
      disorganization of tensin localization and disruption of stress fibers. RV
      increased cell motility and attachment to fibronectin in MCF7 cells submitted to
      mechanical laminar flow stress, and abrogated estrogen-induced MCF7 cancer cell
      invasion. Our data support the conclusion that induction of tensin by RV
      contributes to the chemopreventive and anti-invasive activity of this natural
      dietary compound in tensin-negative and -deficient leukemic cells or epithelioid
      cancers.

PMID- 15735709
TI  - Arsenic trioxide (As(2)O(3)) induces apoptosis through activation of Bax in
      hematopoietic cells.
AB  - This study explores the roles of Bax and other Bcl-2 family members play in
      arsenic trioxide (As(2)O(3))-induced apoptosis. We showed that As(2)O(3)
      treatment triggered Bax conformational change and subsequent translocation from
      cytosol to mitochondria to form various multimeric homo-oligomers in IM-9 cells.
      On the other hand, human leukemic Jurkat cells deficient in Bax showed
      dramatically reduced apoptosis in response to As(2)O(3). Stable overexpression of
      Bcl-2 in IM-9 cells (IM-9/Bcl-2) inhibited As(2)O(3)-mediated Bax activation and
      apoptosis, and this inhibition could be partially averted by cell-permeable Bid
      Bcl-2 homology (BH)3 peptide. Meanwhile, Bax conformational change and
      oligomerization induced by As(2)O(3) were not inhibited by the pancaspase
      inhibitor z-VAD-fmk, although Bid cleavage could be completely abolished. Bax
      activation by As(2)O(3) seemed to require stress-induced intracellular reactive
      oxygen species (ROS), since the ROS scavengers (N-acetyl-L-cysteine and lipoic
      acid) could completely block the conformational change and translocation of Bax
      from cytosol to mitochondria. These data suggest that As(2)O(3) might exert the
      cell killing in part by inducing Bax activation through a Bcl-2-suppressible
      pathway in hematopoietic cells that is caspase independent and intracellular ROS
      regulated.

PMID- 15735710
TI  - The human VE-cadherin promoter is subjected to organ-specific regulation and is
      activated in tumour angiogenesis.
AB  - Vascular endothelial (VE)-cadherin is exclusively expressed at interendothelial
      junctions of normal and tumour vessels. In this report, we characterized the
      transcriptional activity of the human VE-cadherin promoter. Transient
      transfection assays revealed that sequences at positions --1135/-744 and -166/-5
      base pairs are critical for promoter activity in endothelial cells. We show that
      specific sequences in the proximal region interact with Ets and Sp1 family
      members. Transgenic mice were created and the human VE-cadherin promoter was able
      to confer correct temporal and spatial expression on the LacZ gene in embryos. In
      adults, the transgene was specifically and strongly expressed in the lung, heart,
      ovary, spleen and kidney glomeruli, whereas expression was weak or absent in the
      vasculature of other organs, including the brain, thymus, liver and skeletal
      muscle. Neovessels in tumour grafts and Matrigel implants harboured strong
      stainings, indicating that promoter activity is enhanced in angiogenic
      situations. Furthermore, Matrigel and transfection assays showed that VE-cadherin
      promoter is subjected to bFGF induction. Transgene expression was also noticed in
      extravascular sites of the central nervous system, suggesting that silencer
      elements may be located elsewhere in the gene. These results are a first step
      towards addressing the organ- and tumour-specific regulation of the VE-cadherin
      gene.

PMID- 15735712
TI  - Distinct transduction mechanisms of cyclooxygenase 2 gene activation in tumour
      cells after photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a minimally invasive treatment for cancer and
      several noncancerous proliferating cell diseases. PDT relies on the uptake of a
      photosensitizing compound by the pathologic tissue followed by a selective
      irradiation with visible light, which leads to oxidative stress-mediated cell
      death. However, some studies showed that PDT induces the release of proangiogenic
      factors, such as vascular endothelial growth factor, and/or cyclooxygenase-2 (COX
      2), thereby promoting cancer cell regrowth following PDT. In this work, we
      focused on the molecular mechanisms regulating COX-2 expression after low-dose
      PDT in two cancer cell lines, namely HeLa and T24. We report that PDT induces COX
      2 expression in these cells and this expression is mainly due to nuclear factor
      kappa B (NF-kappaB)-dependent transcription of cox-2 gene without any post
      transcriptional regulation. However, the transduction mechanism leading to NF
      kappaB activation and subsequent cox-2 gene transcription differs in both cell
      types. In T24, NF-kappaB activation occurs through a protein kinase C (PKC)alpha-
      and phosphoinositide-3-kinase (PI3K)-dependent I kappa B kinase (IKK) complex
      activation, whereas in HeLa cells, NF-kappaB activation is mediated by PKC- and
      PI3K-independent IKK complex activation.

PMID- 15735711
TI  - Accumulation and altered localization of telomere-associated protein TRF2 in
      immortally transformed and tumor-derived human breast cells.
AB  - We have used cultured human mammary epithelial cells (HMEC) and breast tumor
      derived lines to gain information on defects that occur during breast cancer
      progression. HMEC immortalized by a variety of agents (the chemical carcinogen
      benzo(a)pyrene, oncogenes c-myc and ZNF217, and/or dominant negative p53 genetic
      suppressor element GSE22) displayed marked upregulation (10-15 fold) of the
      telomere-binding protein, TRF2. Upregulation of TRF2 protein was apparently due
      to differences in post-transcriptional regulation, as mRNA levels remained
      comparable in finite lifespan and immortal HMEC. TRF2 protein was not upregulated
      by the oncogenic agents alone in the absence of immortalization, nor by
      expression of exogenously introduced hTERT genes. We found TRF2 levels to be at
      least twofold higher than in control cells in 11/15 breast tumor cell lines,
      suggesting that elevated TRF2 levels are a frequent occurrence during the
      transformation of breast tumor cells in vivo. The dispersed distribution of TRF2
      throughout the nuclei in some immortalized and tumor-derived cells indicated that
      not all the TRF2 was associated with telomeres in these cells. The process
      responsible for accumulation of TRF2 in immortalized HMEC and breast tumor
      derived cell lines may promote tumorigenesis by contributing to the cells'
      ability to maintain an indefinite lifespan.

PMID- 15735713
TI  - Mutation frequencies and AID activation state in B-cell lymphomas from Ung
      deficient mice.
AB  - B-cell lymphomas arising in lymph nodes and spleen of aging mice deficient in the
      Ung DNA glycosylase were recovered, dispersed, grown in short-term culture, and
      CD19-positive B-cells retrieved and analysed. Several tumors as well as controls
      only expressed detectable amounts of the Aid deaminase after mitogenic
      stimulation, as estimated by real-time PCR of transcripts. However, one unusually
      large lymph node tumor expressed a high level of Aid constitutively. This
      particular tumor also showed a substantially increased mutation frequency in the
      Aid gene itself as well as in the bcl-6 and c-myc genes, but not in the p53 gene,
      consistent with aberrant somatic hypermutation. Other B-cell lymphomas from Ung(
      /-) mice exhibited a modest increase in mutation frequency.

PMID- 15735714
TI  - An integrated data analysis approach to characterize genes highly expressed in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the major causes of cancer deaths
      worldwide. New diagnostic and therapeutic options are needed for more effective
      and early detection and treatment of this malignancy. We identified 703 genes
      that are highly expressed in HCC using DNA microarrays, and further characterized
      them in order to uncover novel tumor markers, oncogenes, and therapeutic targets
      for HCC. Using Gene Ontology annotations, genes with functions related to cell
      proliferation and cell cycle, chromatin, repair, and transcription were found to
      be significantly enriched in this list of highly expressed genes. We also
      identified a set of genes that encode secreted (e.g. GPC3, LCN2, and DKK1) or
      membrane-bound proteins (e.g. GPC3, IGSF1, and PSK-1), which may be attractive
      candidates for the diagnosis of HCC. A significant enrichment of genes highly
      expressed in HCC was found on chromosomes 1q, 6p, 8q, and 20q, and we also
      identified chromosomal clusters of genes highly expressed in HCC. The microarray
      analyses were validated by RT-PCR and PCR. This approach of integrating other
      biological information with gene expression in the analysis helps select
      aberrantly expressed genes in HCC that may be further studied for their
      diagnostic or therapeutic utility.

PMID- 15735715
TI  - TGFalpha expression impairs Trastuzumab-induced HER2 downregulation.
AB  - The HER2 gene encodes a tyrosine kinase receptor overexpressed in 25-30% of human
      breast cancers. Clinical trials have shown the efficacy of the anti-HER2
      monoclonal antibody Trastuzumab in metastatic breast cancer patients.
      Nevertheless, 70% of patients are unresponsive from start of treatment and nearly
      all become unresponsive during treatment. Possible mechanisms for these failures
      could depend on impairment of the machinery responsible for receptor
      downregulation. To test this hypothesis, we analysed the genomic sequences
      encoding regions known to be critical for HER2 downregulation, of both HER2 and
      of the ubiquitin ligase Cbl. We investigated 63 breast cancers, and found no
      mutations in these regions. We thus considered alternative mechanisms -- such as
      TGFalpha production -- possibly interfering with HER2 downregulation. In selected
      cases, by comparing breast cancer neoplastic tissue before and after Trastuzumab
      treatment, we found induction of TGFalpha expression. Moreover, by in vitro
      expression of exogenous TGFalpha in breast cancer cells, we observed a dramatic
      reduction in Trastuzumab-induced HER2 endocytosis, downregulation and cell growth
      inhibition. Our results suggest that unresponsiveness to Trastuzumab may not be
      due to intrinsic defects in the machinery responsible for HER2 downregulation,
      but can be associated with a TGFalpha-related mechanism of escape to HER2
      downregulation.

PMID- 15735716
TI  - Visinin-like protein-1 is a potent inhibitor of cell adhesion and migration in
      squamous carcinoma cells.
AB  - Tumor cell invasion is a highly integrated and complex process comprising several
      biologically distinct functions such as cell adhesion, motility, proteolysis,
      etc. Visinin-like protein-1 (VILIP-1), a member of the neuronal EF-hand calcium
      sensor protein family, plays a role in regulating tumor cell invasiveness of
      mouse squamous cell carcinoma (SCC). VILIP-1 enhances cyclic adenosine
      monophosphate levels through PKA induction. However, the mechanism by which VILIP
      1 reduces cell invasiveness is not well understood. In this study, we show that
      VILIP-1 decreased cell adhesion and migration/invasiveness of highly invasive
      mouse SCC cells. Forced expression of VILIP-1 reduced cell adhesion to
      fibronectin in parallel to downregulating alphav and alpha5 integrin subunit
      levels. VILIP-1 overexpression also led to decreased migration ability.
      Conversely, short hairpin RNA-mediated VILIP-1 knock-down of SCC cells'
      characterized by little or no invasiveness, correlated with increased adhesion to
      fibronectin and enhanced expression of alphav and alpha5 integrin subunits
      together with increased cell migration. Function-blocking assays with inhibitory
      anti-alpha5 and anti-alphav integrin antibodies showed that both subunits
      contributed to cell adhesion, migration, and invasiveness of highly invasive SCC
      cell lines. These results point to a critical role of VILIP-1 in regulating cell
      adhesion and migration by downregulation of fibronectin receptor expression.
      Decreased or absent VILIP-1 expression in SCC cell subpopulations may lead to a
      more advanced malignant phenotype characterized by changes in adhesive ability
      and increased cell motility, suggestive of a tumor suppressor function.

PMID- 15735717
TI  - Inactivation of TGF-beta signaling in hepatocytes results in an increased
      proliferative response after partial hepatectomy.
AB  - The transforming growth factor beta (TGF-beta) signaling pathway, which is
      activated by the TGF-beta receptor complex consisting of type I and type II TGF
      beta receptors (TGFBR1 and TGFBR2), regulates cell growth and death. TGF-beta and
      components of its signaling pathway, particularly TGFBR2, have been implicated as
      tumor suppressor genes and important antimitogenic factors in the
      gastrointestinal tract and liver. An in vivo approach to study these effects has
      been hindered by the embryonic lethality of Tgfbr2(-/-) mice and poor viability
      of the Tgfb1(-/-) mice. Consequently, we have developed a hepatocyte-specific
      Tgfbr2 knockout mouse, the Alb-cre Tgfbr2(flx/flx) mouse, to study the
      physiologically relevant effects of TGF-beta signaling on epithelial cell
      proliferation in vivo. After 70% hepatectomy, we observed increased proliferation
      and an increased liver mass : body weight ratio in the Alb-cre Tgfbr2(flx/flx)
      mice compared to Tgfbr2(flx/flx) mice. We also observed decreased expression and
      increased phosphorylation of p130 in the livers from the Alb-cre Tgfbr2(flx/flx)
      mice as well as increased expression of cyclin E, which is transcriptionally
      regulated, in part, by p130:E2F4. Consistent with these results, in a hepatocyte
      cell line derived from the Tgfbr2(flx/flx) mice, we found that TGF-beta increases
      the nuclear localization of E2F4, and presumably the transcriptional repression
      of the p130:E2F4 complex. Thus, we have demonstrated that TGF-beta signaling in
      vivo regulates the mitogenic response in the regenerating liver, affecting the
      liver mass : body weight ratio after partial hepatectomy, and that these
      mitogenic responses are accompanied by alterations in p130 expression and
      phosphorylation, implicating p130 as one of the proteins regulated in vivo by TGF
      beta during liver regeneration.

PMID- 15735718
TI  - Induction of p21 by p53 following DNA damage inhibits both Cdk4 and Cdk2
      activities.
AB  - DNA damage often activates the p53-p21 pathway and causes G(1)-phase arrest in
      mammalian cells. Although there is ample evidence that p21 induction by p53 leads
      to Cdk2 inhibition, it is unclear whether this checkpoint event also leads to
      Cdk4 inhibition. Diaminocyclohexane(trans-diacetato)(dichloro) platinum(IV)
      (DAP), a platinum-based coordination complex, is a DNA-damaging agent that is
      effective against a variety of tumor cells resistant to the parental drug
      cisplatin. Our previous studies established that treatment of human cancer cells
      with low effective concentrations of DAP specifically activates the G(1)-phase
      checkpoint and simultaneously inhibit Cdk4 and Cdk2 activities. Here we
      demonstrate that DAP treatment of human cancer cells activates the p53-p21
      pathway without activating other known mechanisms that inhibit Cdk4 and Cdk2
      activities. The induced p21 binds to both the Cdk4/cyclin D and Cdk2/cyclin E
      complexes and inhibits both of their kinase activities. Conversely, inhibition of
      p21 induction by cycloheximide or by p21 gene deletion prevents DAP-induced
      inhibition of Cdk4 and Cdk2 activities. Attenuated p53 expression and p21
      induction also eliminates DAP-induced G(1)-phase arrest and inhibition of Cdk4
      and Cdk2 activities. Together, these findings establish that activation of the
      p53-p21 pathway is responsible for the DAP-induced G(1)-phase checkpoint response
      and provide the first solid evidence that p21 induction by p53 during a DNA
      damage-induced G(1)-phase checkpoint response inhibits both Cdk4 and Cdk2
      activities.

PMID- 15735719
TI  - Conditional inhibition of cancer cell proliferation by tetracycline-responsive,
      H1 promoter-driven silencing of PLK1.
AB  - RNA interference (RNAi) is a powerful tool for studying gene function. We
      developed an inducible genetic element for short interfering RNA-mediated gene
      silencing. This system uses a tetracycline (Tet)-responsive derivative of the H1
      promoter and the Tet repressor (TetR) for conditional expression of short hairpin
      RNA (shRNA) in HeLa cells. Promoter constructs were generated, which contain the
      Tet operator (TetO) derived from a prokaryotic Tet resistance transposon upstream
      and/or downstream of the TATA box. To quantify the response of controllable
      transcription units for shRNA expression, we examined the functional activity of
      polo-like kinase 1 (PLK1), a key component of mitotic progression, that is
      overexpressed in many human tumors. Cotransfection of plasmids for the expression
      of TetR and shRNA/PLK1 under the control of an H1 promoter-variant carrying TetO
      upstream of the TATA box did not alter PLK1 expression and proliferation
      properties of HeLa cells in the absence of doxycycline. Addition of the
      antibiotic led to marked downregulation of endogenous PLK1 accompanied by strong
      inhibition of cellular proliferation. Our data indicate that an inducible
      transcription system for shRNAs based on the human H1 promoter could be a
      versatile tool for controlled gene silencing in vitro.

PMID- 15735720
TI  - Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor
      activity.
AB  - Constitutive activation of the JAK/STAT3 pathway is a major contributor to
      oncogenesis. In the present study, structure-activity relationship (SAR) studies
      with five cucurbitacin (Cuc) analogs, A, B, E, I, and Q, led to the discovery of
      Cuc Q, which inhibits the activation of STAT3 but not JAK2; Cuc A which inhibits
      JAK2 but not STAT3 activation; and Cuc B, E, and I, which inhibit the activation
      of both. Furthermore, these SAR studies demonstrated that conversion of the C3
      carbonyl of the cucurbitacins to a hydroxyl results in loss of anti-JAK2
      activity, whereas addition of a hydroxyl group to C11 of the cucurbitacins
      results in loss of anti-STAT3 activity. Cuc Q inhibits selectively the activation
      of STAT3 and induces apoptosis without inhibition of JAK2, Src, Akt, Erk, or JNK
      activation. Furthermore, Cuc Q induces apoptosis more potently in human and
      murine tumors that contain constitutively activated STAT3 (i.e., A549, MDA-MB
      435, and v-Src/NIH 3T3) as compared to those that do not (i.e., H-Ras/NIH 3T3,
      MDA-MB-453, and NIH 3T3 cells). Finally, in a nude mouse tumor xenograft model,
      Cuc Q, but not Cuc A, suppresses tumor growth indicating that JAK2 inhibition is
      not sufficient to inhibit tumor growth and suggesting that the ability of Cuc Q
      to inhibit tumor growth is related to its anti-STAT3 activity. These studies
      further validate STAT3 as a drug discovery target and provide evidence that
      pharmacological agents that can selectively reduce the P-STAT3 levels in human
      cancer cells result in tumor apoptosis and growth inhibition.

PMID- 15735721
TI  - Stat3 regulates genes common to both wound healing and cancer.
AB  - Wound healing and cancer are both characterized by cell proliferation, remodeling
      of extracellular matrix, cell invasion and migration, new blood vessel formation,
      and modulation of blood coagulation. The mechanisms that link wound healing and
      cancer are poorly understood. We report here that Stat3, a common signaling
      mechanism involved in oncogenesis and tissue injury, regulates a common set of
      genes involved in wound healing and cancer. Using oligonucleotide gene arrays and
      quantitative real-time PCR, we evaluated changes in global gene expression
      resulting from expression of Stat3 in lung epithelial cells. We report here
      previously uncharacterized genes induced by Stat3 implicated in signaling
      pathways common to both wound healing and cancer including cell invasion and
      migration, angiogenesis, modulation of coagulation, and repression of interferon
      inducible genes. Consistent with these results, we found increased Stat3 activity
      associated with wound healing in chronically inflamed mouse lungs and increased
      Stat3 activity was identified at the leading edge of lung tumors invading
      adjacent nontumor stroma. These findings provide a molecular basis for
      understanding cancer as a deregulation of normal wound healing processes.

PMID- 15735722
TI  - Apoptosis related to telomere instability and cell cycle alterations in human
      glioma cells treated by new highly selective G-quadruplex ligands.
AB  - Telomerase represents a relevant target for cancer therapy. Molecules able to
      stabilize the G-quadruplex (G4), a structure adopted by the 3'-overhang of
      telomeres, are thought to inhibit telomerase by blocking its access to telomeres.
      We investigated the cellular effects of four new 2,6-pyridine-dicarboxamide
      derivatives displaying strong selectivity for G4 structures and strong inhibition
      of telomerase in in vitro assays. These compounds inhibited cell proliferation at
      very low concentrations and then induced a massive apoptosis within a few days in
      a dose-dependent manner in cultures of three telomerase-positive glioma cell
      lines, T98G, CB193 and U118-MG. They had also antiproliferative effects in SAOS
      2, a cell line in which telomere maintenance involves an alternative lengthening
      of telomeres (ALT) mechanism. We show that apoptosis was preceded by multiple
      alterations of the cell cycle: activation of S-phase checkpoints, dramatic
      increase of metaphase duration and cytokinesis defects. These effects were not
      associated with telomere shortening, but they were directly related to telomere
      instability involving telomere end fusion and anaphase bridge formation. Pyridine
      based G-quadruplex ligands are therefore promising agents for the treatment of
      various tumors including malignant gliomas.

PMID- 15735723
TI  - Uncoupling of genomic instability and tumorigenesis in a mouse model of Burkitt's
      lymphoma expressing a conditional box II-deleted Myc protein.
AB  - Burkitt's lymphomas (BL) are characterized by the constitutive expression of c
      Myc protein. In total, 50-60% of all BL cells carry mutant c-Myc proteins. Using
      a mouse model of spontaneously immortalized pro-B-lymphocytes (Ba/F3), we have
      investigated genomic instability mediated by the conditional expression of either
      wild-type (WT) or deletion box II Delta106-Myc proteins. We found that both
      proteins mediate common as well as differing types of chromosomal rearrangements
      as documented by spectral karyotyping (SKY). A higher level of genomic
      instability is induced by the Delta106-Myc protein. To examine the tumorigenic
      potential of WT or Delta106-driven Ba/F3 cells, in vivo tumorigenesis studies
      were performed in SCID mice. Under the experimental conditions of this study, WT
      but not Delta106-Myc expressing Ba/F3 cells triggered tumorigenesis in SCID mice.
      Therefore, the genomic instability phenotype induced by Delta106-Myc can be
      genetically uncoupled from its tumorigenic potential.

PMID- 15735724
TI  - Mayven induces c-Jun expression and cyclin D1 activation in breast cancer cells.
AB  - Mayven is a member of the kelch-related superfamily of proteins, characterized by
      a series of 'kelch' repeats at their carboxyl terminus and a BTB/POZ domain at
      their NH2-terminus. Little is known about the role of Mayven in cancer. Here, we
      report that Mayven expression was abundant and diffuse in primary human
      epithelial breast tumor cells as compared to normal breast epithelial cells,
      where Mayven was detected in the normal breast layer of the mammary ducts.
      Overexpression of Mayven resulted in an induction of c-Jun protein levels, as
      well as increased AP-1 (activating protein 1) transcriptional activity in MCF-7
      and T47D breast cancer cells through its BTB/POZ domain. Furthermore, Mayven
      activated c-Jun N-terminal kinase in breast cancer cells. Mayven, through its
      BTB/POZ domain, induced cyclin D1 expression and cyclin D1 promoter activity and
      promoted cell cycle progression from the G1 to S phase. MCF-7 cells transduced
      with the recombinant retroviral sense Mayven (pMIG-W-Mayven) showed significant
      induction of c-Jun and cyclin D1 mRNA expression and activities as compared to
      the retroviral vector alone, while MCF-7 cells transduced by the recombinant
      retroviral antisense Mayven (pMIG-W-Mayven-AS) demonstrated a significant
      decrease in c-Jun and cyclin D1 expression and activities. Given the crucial
      functions of cyclin D1 and AP-1 signaling in oncogenesis, our results strongly
      suggest that overexpression of Mayven may promote tumor growth through c-Jun and
      cyclin D1.

PMID- 15735725
TI  - Suppression of cell migration by protein kinase Cdelta.
AB  - The ability of cancer cells to migrate is strongly correlated with malignant
      progression and metastasis. Survival signals that suppress apoptosis have also
      been linked to increased cell motility. We previously reported that suppression
      of protein kinase Cdelta (PKCdelta) provided survival signals in a rat fibroblast
      model system. These studies have been extended to human breast cancer cells with
      differential cell motilities and PKCdelta levels. BT-549 cells, which lack
      detectable expression of PKCdelta, migrate very efficiently, whereas MCF-7 cells,
      which express high levels of PKCdelta, migrate very poorly. Ectopic expression of
      PKCdelta suppressed cell migration in the BT-549 cells, and downregulation of
      PKCdelta enhanced cell migration in the MCF-7 cells. Downregulation of PKCdelta
      in the MCF-7 cells also led to increased secretion of the matrix metalloprotease
      MMP-9. The migration of mouse embryo fibroblasts (MEFs) from wild type and
      PKCdelta knockout mice was also examined and MEFs from PKCdelta knockout mice had
      a five-fold increase in cell migration relative to the wild-type MEFs. These data
      provide evidence that PKCdelta suppresses cell migration in both human breast
      cancer cells and in primary mouse fibroblasts, and indicate that the loss of
      PKCdelta in human cancers could contribute to both cell survival and metastasis.

PMID- 15735726
TI  - Analysis of methylation-sensitive transcriptome identifies GADD45a as a
      frequently methylated gene in breast cancer.
AB  - Treatment of the breast cancer cell line, MDAMB468 with the DNA methylation
      inhibitor, 5-azacytidine (5-AzaC) results in growth arrest, whereas the growth of
      the normal breast epithelial line DU99 (telomerase immortalized) is relatively
      unaffected. Comparing gene expression profiles of these two lines after 5-AzaC
      treatment, we identified 36 genes that had relatively low basal levels in
      MDAMB468 cells compared to the DU99 line and were induced in the cancer cell line
      but not in the normal breast epithelial line. Of these genes, 33 have associated
      CpG islands greater than 300 bp in length but only three have been previously
      described as targets for aberrant methylation in human cancer. Northern blotting
      for five of these genes (alpha-Catenin, DTR, FYN, GADD45a, and Zyxin) verified
      the array results. Further analysis of one of these genes, GADD45a, showed that 5
      AzaC induced expression in five additional breast cancer cell lines with little
      or no induction in three additional lines derived from normal breast epithelial
      cells. The CpG island associated with GADD45a was analysed by bisulfite
      sequencing, sampling over 100 CpG dinucleotides. We found that four CpG's,
      located approximately 700 bp upstream of the transcriptional start site are
      methylated in the majority of breast cancer cell lines and primary tumors but not
      in DNA from normal breast epithelia or matched lymphocytes from cancer patients.
      Therefore, this simple method of dynamic transcriptional profiling yielded a
      series of novel methylation-sensitive genes in breast cancer including the BRCA1
      and p53 responsive gene, GADD45a.

PMID- 15735727
TI  - Regulation of epidermal apoptosis and DNA repair by E2F1 in response to
      ultraviolet B radiation.
AB  - The E2F1 transcription factor regulates the expression of genes involved in cell
      proliferation, apoptosis and DNA repair. Following DNA damage, E2F1 is
      phosphorylated and stabilized, but the physiological role of E2F1 in the response
      to DNA damage is unclear. We find that mice lacking E2F1 have increased levels of
      epidermal apoptosis compared to wild-type mice following exposure to ultraviolet
      B (UVB) radiation. Moreover, transgenic overexpression of E2F1 in basal layer
      keratinocytes suppresses apoptosis induced by UVB. Inhibition of UVB-induced
      apoptosis by E2F1 is unexpected given that most studies have demonstrated a
      proapoptotic function for E2F1. E2F1-mediated suppression of apoptosis does not
      involve alterations in mitogen-activated protein kinase activation or Bcl-2
      downregulation in response to UVB and is independent of p53. Instead, inhibition
      of UVB-induced apoptosis by E2F1 correlates with a stimulation of DNA repair.
      Mice lacking E2F1 are impaired for the removal of DNA photoproducts, while E2F1
      transgenic mice repair UVB-induced DNA damage at an accelerated rate compared to
      wild-type mice. These findings suggest that E2F1 participates in the response to
      UVB by promoting DNA repair and suppressing apoptosis.

PMID- 15735728
TI  - Chronic myeloid leukaemia: an investigation into the role of Bcr-Abl-induced
      abnormalities in glucose transport regulation.
AB  - In chronic myeloid leukaemia (CML) expression of the chimeric tyrosine kinase,
      Bcr-Abl, promotes the inappropriate survival of haemopoietic stem cells by a
      nonautocrine mechanism in the absence of IL-3. Stimulation of glucose uptake
      appears to play an important role in the suppression of apoptosis by this
      cytokine in normal haemopoietic cells. To investigate whether the cell survival
      mechanisms mediated by the oncoprotein and cytokine showed any similarities, we
      employed a haemopoietic cell line, TonB210, engineered for inducible expression
      of Bcr-Abl. Tyrosine kinase expression in cytokine-deprived cells was found to
      mimic the effect of IL-3 in maintaining a higher V(max) for hexose uptake. In
      both IL-3- treated cells and those expressing Bcr-Abl, high rates of hexose
      uptake were associated with the retention at the cell surface of approximately
      80% of the total cellular content of the GLUT1 glucose transporter. In contrast,
      treatment of Bcr-Abl-expressing cells for 6 h with the Bcr-Abl kinase inhibitor
      Glivec (10 muM), in the absence of IL-3, led to internalization of approximately
      90% of the cell-surface transporters and drastically decreased (4.4+/-0.9 (mean+/
      s.e.m., 4)-fold) the V(max) for hexose uptake, without significant effect on the
      K(m) for this process or on the total cellular transporter content. These effects
      were not the result of any significant loss in cell viability, and preceded the
      onset of apoptosis caused by inhibition of Bcr-Abl. Both IL-3 treatment and
      expression of Bcr-Abl led to enhanced phosphorylation of Akt (protein kinase B).
      The stimulation of transport by IL-3 and Bcr-Abl in TonB210 cells was inhibitable
      by phosphatidylinositol 3-kinase inhibitors, indicating the involvement of this
      kinase in the signal transduction pathway. These findings suggest that inhibition
      of glucose transport plays an important role in the therapeutic action of Glivec,
      and that the signal transduction pathways involved in transport stimulation by
      Bcr-Abl may offer novel therapeutic targets for CML.

PMID- 15735729
TI  - Enhanced oncolysis by a tropism-modified telomerase-specific replication
      selective adenoviral agent OBP-405 ('Telomelysin-RGD').
AB  - Replication-competent oncolytic viruses are being developed for human cancer
      therapy. We previously reported that an attenuated adenovirus (OBP-301,
      'Telomelysin'), in which the hTERT promoter element drives expression of E1A and
      E1B genes linked with an IRES, could replicate in cancer cells, and causes
      selective lysis of cancer cells. We further constructed OBP-405 ('Telomelysin
      RGD') that contains an RGD motif in the HI loop of the fiber knob. We examined
      whether OBP-405 could be effective in overcoming the limitations of OBP-301,
      specifically their inefficient infection into cells lacking the primary receptor,
      the coxsackievirus and adenovirus receptor (CAR). By flow cytometric analysis,
      H1299 (lung) and SW620 (colorectal) tumor cells showed high levels of CAR
      expression, whereas LN444 (glioblastoma), LNZ308 (glioblastoma), and H1299-R5
      (lung) tumor cells were negative for CAR expression. A quantitative real-time PCR
      analysis demonstrated that fiber-modified OBP-405 infected more efficiently than
      OBP-301, although the intracellular replication rate of both viruses was
      consistent. The comparative antitumor effect of fiber-modified OBP-405 and
      unmodified OBP-301 for human cancer cells was evaluated in vitro by XTT assay as
      well as in vivo by using athymic mice carrying xenografts. OBP-405 had a profound
      oncolytic effect on human cancer cell lines compared to OBP-301, in particular on
      cells with low CAR expression. Intratumoral injection of 10(7) plaque-forming
      units of OBP-405 into CAR-negative H1299-R5 lung tumor xenografts in nu/nu mice
      resulted in a significant inhibition of tumor growth and long-term survival in
      all treated mice. Moreover, selective replication of OBP-405 in the distant,
      uninjected H1299-R5 tumors was demonstrated. Our results suggest that fiber
      modified replication-competent adenovirus OBP-405 exhibits a broad target range
      by increasing infection efficiency, an outcome that has important implications
      for the treatment of human cancers.

PMID- 15735730
TI  - RNA silencing of S-phase kinase-interacting protein 2 inhibits proliferation and
      centrosome amplification in lung cancer cells.
AB  - The S-phase kinase-associated protein-2 (SKP2) plays a key role in ubiquitin
      mediated proteolysis, which results in the progression of cells from a quiescence
      to proliferative state. SKP2 is overexpressed in a variety of tumors. In this
      study, we used small interfering RNAs (siRNAs) to inhibit the SKP2 expression in
      lung cancer cells and thereby investigate the role of SKP2 in lung tumorigenesis.
      Three lung cancer cell lines were transfected with siRNAs targeted against SKP2.
      SKP2-siRNAs specifically and efficiently reduced the levels of the SKP2 protein
      by 90% 48 h after transfection in all cell lines. In the A549 and H1792 cells,
      p27 expression was increased and the increase was inversely proportional to the
      level of SKP2; cell proliferation was reduced to 12 and 28%, respectively;
      apoptosis was increased to 36 and 30%, respectively; 36 and 28% of cells
      accumulated in the sub-G1 phase, respectively; and the population of cells in the
      G1 phase was decreased to 37 and 41%, respectively. In addition, the SKP2
      depleted A549 and H1792 cells showed decreased levels of cyclin E/CDK2.
      Correspondingly, only 4 and 6% of the treated A549 and H1792 cells had multiple
      centrosomes, respectively, compared with 43 and 46% of the control cells,
      respectively. These results imply that SKP2 plays an oncogenic role in lung
      cancer and that SKP2 silencing may be useful in the treatment of lung cancer.

PMID- 15735731
TI  - Retinoic acid stabilizes p27Kip1 in EBV-immortalized lymphoblastoid B cell lines
      through enhanced proteasome-dependent degradation of the p45Skp2 and Cks1
      proteins.
AB  - Retinoic acid (RA) arrests the growth of EBV-immortalized lymphoblastoid B cell
      lines (LCLs) by upregulating the cyclin-dependent kinase inhibitor p27Kip1. Here,
      we show that in LCLs, RA inhibits ubiquitination and proteasome-dependent
      degradation of p27Kip1, a phenomenon that is associated with downregulation of
      Thr187 phosphorylation of the protein, whereas the phosphorylation on Ser10 is
      unaffected. Furthermore, we demonstrate that RA downregulates the expression of
      the p45Skp2 and Cks1 proteins, two essential components of the SCF(Skp2)
      ubiquitin ligase complex that target p27Kip1 for degradation. Downregulation of
      p45Skp2)and Cks1 occurs before the onset of growth arrest and is due to enhanced
      proteasome-mediated proteolysis of these proteins. Moreover, overexpression of
      p45Skp2 in DG75 cells prevents p27Kip1 protein accumulation and promotes
      resistance to the antiproliferative effects of RA. Treatment with Leptomycin B
      (LMB) blocked the translocation of p27Kip1 to the cytoplasm and prevented its
      degradation, indicating that CRM1-dependent nuclear export is required for
      p27Kip1 degradation. The shuttle protein p38Jab1, however, does not accumulate in
      the nucleus upon LMB treatment, nor does it interact with p27Kip1. Conversely,
      p45Skp2 is associated with p27Kip1 both in the nucleus and in the cytoplasm,
      accumulating within the nuclei after exposure to LMB and co-localizing with the
      exportin CRM1, suggesting a possible involvement of p45Skp2 in CRM1-dependent
      nuclear export of p27Kip1. These results indicate that downregulation of p45Skp2
      is a key element underlying RA-induced p27Kip1 stabilization in B cells,
      resulting in an impaired targeting of the protein to the ubiquitin-proteasome
      pathway and probably contributing to the nuclear accumulation of p27Kip1.

PMID- 15735732
TI  - In vitro and in vivo analysis of the interaction between 5.8S rRNA and ARF
      protein reveal a new difference between murine p19ARF and human p14ARF.
AB  - Both human and murine ARF proteins have been recently reported to impair rRNA
      maturation and ribosomes biogenesis through a p53-independent pathway. A specific
      interaction has been established between 5.8S rRNA and the murine p19ARF specie.
      We report here, by use of both in vitro and ChIP-RNA assays, the absence of any
      interaction between the human p14ARF and the homologous 5.8S rRNA. Our data are
      not consistent with the involvement of a 5.8S-p14ARF complex in ribosome
      biogenesis in man. Rather they suggest that the human protein does not require
      such an interaction to achieve a similar function. This result is a new argument
      in favour of functional differences between human and murine ARF proteins.

PMID- 15735733
TI  - Microsatellite instability of selective target genes in HNPCC-associated colon
      adenomas.
AB  - Microsatellite instability (MSI) occurs in most hereditary nonpolyposis
      colorectal cancers (HNPCC) and less frequently in sporadic tumors as the result
      of DNA mismatch repair (MMR) deficiency. Instability at coding microsatellites
      (cMS) in specific target genes causes frameshift mutations and functional
      inactivation of affected proteins, thereby providing a selective growth advantage
      to MMR deficient cells. At present, little is known about Selective Target Gene
      frameshift mutations in preneoplastic lesions. In this study, we examined 30
      HNPCC-associated MSI-H colorectal adenomas of different grades of dysplasia for
      frameshift mutations in 26 cMS-bearing genes, which, according to our previous
      model, represent Selective Target genes of MSI. About 30% (8/26) of these genes
      showed a high mutation frequency (> or =50%) in colorectal adenomas, similar to
      the frequencies reported for colorectal carcinomas. Mutations in one gene (PTHL3)
      occurred significantly less frequently in MSI adenomas compared to published
      mutation rates in MSI carcinomas (36.0 vs 85.7%, P=0.023). Biallelic inactivation
      was observed in nine genes, thus emphasizing the functional impact of cMS
      instability on MSI tumorigenesis. Some genes showed a high frequency of
      frameshift mutations already at early stages of MSI colorectal tumorigenesis that
      increased with grade of dysplasia and transition to carcinoma. These include
      known Target Genes like BAX and TGFBR2, as well as three novel candidates, MACS,
      NDUFC2, and TAF1B. Overall, we have identified genes of potential relevance for
      the initiation and progression of MSI tumorigenesis, thus representing promising
      candidates for novel diagnostic and therapeutic approaches directed towards MMR
      deficient tumors.

PMID- 15735734
TI  - EWS-FLI1 target genes recovered from Ewing's sarcoma chromatin.
AB  - In all, 85% of Ewing's sarcoma family tumors (ESFT), a neoplasm of unknown
      histogenesis, express EWS-FLI1 transcription factor gene fusions. To characterize
      direct target genes avoiding artificial model systems, we cloned genomic DNA from
      ESFT chromatin precipitating with EWS-FLI1. We now present a comprehensive list
      of 99 putative transcription factor targets identified, for the first time, by a
      hypothesis-free approach based on physical interaction. Gene-derived chromatin
      fragments co-precipitating with EWS-FLI1 were nonrandomly distributed over the
      human genome and localized predominantly to the upstream region and the first two
      introns of the genes. At least 20% of putative direct EWS-FLI1 targets were
      neural genes. One-third of genes recovered showed a significant ESFT-specific
      expression pattern and were found to be altered upon RNAi-mediated knockdown of
      EWS-FLI1. Among them, MK-STYX, encoding a MAP kinase phosphatase-like protein,
      was consistently expressed in ESFT. EWS-FLI1 was found to drive MK-STYX
      expression by binding to a single ETS binding motif within the first gene intron.
      MK-STYX serves as precedence for successful recovery of direct EWS-FLI1 targets
      from the authentic ESFT cellular context, the most relevant system to study
      oncogenic mechanisms for the discovery of new therapeutic targets in this
      disease.

PMID- 15735735
TI  - Ubiquitination and degradation of the Arg tyrosine kinase is regulated by
      oxidative stress.
AB  - The c-Abl and Arg nonreceptor tyrosine kinases are activated in the response of
      cells to oxidative stress. The present studies demonstrate that treatment of
      cells with 0.1 mM H2O2 is associated with increased tyrosine phosphorylation of
      Arg and little effect on Arg levels. By contrast, exposure to 1.0 mM H2O2
      decreased Arg phosphorylation. Treatment with 1.0 mM H2O2 was also associated
      with ubiquitination and degradation of Arg. The results show that Arg is
      stabilized in response to 0.1 mM H2O2 by autophosphorylation of Y-261, consistent
      with involvement of the Arg kinase function in regulating Arg levels. The results
      further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly
      confers Arg stabilization. In concert with these results, phosphorylation of Arg
      on Y-261 blocked H2O2-induced ubiquitination and thereby Arg degradation and
      inactivation. These findings demonstrate that Arg phosphorylation and degradation
      are differentially regulated by the degree of oxidative stress, and that Arg
      stability is conferred by phosphorylation of Y-261.

PMID- 15735737
TI  - Gene expression profiling of plasma cell dyscrasias reveals molecular patterns
      associated with distinct IGH translocations in multiple myeloma.
AB  - Multiple myeloma (MM) is the most common form of plasma cell dyscrasia,
      characterized by a marked heterogeneity of genetic lesions and clinical course.
      It may develop from a premalignant condition (monoclonal gammopathy of
      undetermined significance, MGUS) or progress from intramedullary to
      extramedullary forms (plasma cell leukemia, PCL). To provide insights into the
      molecular characterization of plasma cell dyscrasias and to investigate the
      contribution of specific genetic lesions to the biological and clinical
      heterogeneity of MM, we analysed the gene expression profiles of plasma cells
      isolated from seven MGUS, 39 MM and six PCL patients by means of DNA microarrays.
      MMs resulted highly heterogeneous at transcriptional level, whereas the
      differential expression of genes mainly involved in DNA metabolism and
      proliferation distinguished MGUS from PCLs and the majority of MM cases. The
      clustering of MM patients was mainly driven by the presence of the most recurrent
      translocations involving the immunoglobulin heavy-chain locus. Distinct gene
      expression patterns have been found to be associated with different lesions: the
      overexpression of CCND2 and genes involved in cell adhesion pathways was observed
      in cases with deregulated MAF and MAFB, whereas genes upregulated in cases with
      the t(4;14) showed apoptosis-related functions. The peculiar finding in patients
      with the t(11;14) was the downregulation of the alpha-subunit of the IL-6
      receptor. In addition, we identified a set of cancer germline antigens
      specifically expressed in a subgroup of MM patients characterized by an
      aggressive clinical evolution, a finding that could have implications for patient
      classification and immunotherapy.

PMID- 15735736
TI  - HPV16 E5 protein disrupts the c-Cbl-EGFR interaction and EGFR ubiquitination in
      human foreskin keratinocytes.
AB  - The E5 protein of human papillomavirus type 16 (HPV16) is a small hydrophobic
      protein, which localizes to the cell membrane, Golgi apparatus and endosomes.
      HPV16 E5 enhances the activation of the epidermal growth factor (EGFR). The
      activated EGFR is downregulated through the endocytic pathway, where E5 has been
      shown to inhibit endosomal acidification and trafficking. Ubiquitination of the
      activated EGFR plays a role in this downregulation. c-Cbl is a ubiquitin ligase
      that associates with the activated EGFR and targets it for degradation. Since E5
      has been shown to form a complex with the EGFR, we tested the hypothesis that E5
      affects the interaction of c-Cbl with the EGFR. We found a significant decrease
      of c-Cbl bound to the EGFR and of ubiquitinated EGFR in the presence of E5. E5
      did not affect c-Cbl steady-state level, phosphorylation or translocation to the
      membrane. This novel result suggests that HPV16 E5 may, at least in part,
      upregulate EGFR-mediated signal transduction by inhibiting the interaction of c
      Cbl with the EGFR, thereby decreasing c-Cbl-mediated degradation of the EGFR.

PMID- 15735738
TI  - [6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP
      kinase and NF-kappaB in phorbol ester-stimulated mouse skin.
AB  - [6]-Gingerol, a pungent ingredient of ginger (Zingiber officinale Roscoe,
      Zingiberaceae), has a wide array of pharmacologic effects. The present study was
      aimed at unraveling the molecular mechanisms underlying previously reported
      antitumor promoting effects of [6]-gingerol in mouse skin in vivo. One of the
      well-recognized molecular targets for chemoprevention is cyclooxygenase-2 (COX-2)
      that is abnormally upregulated in many premalignant and malignant tissues and
      cells. In our present study, topical application of [6]-gingerol inhibited COX-2
      expression in mouse skin stimulated with a prototype tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA). Since the transcription factor nuclear
      factor-kappaB (NF-kappaB) is known to regulate COX-2 induction, we attempted to
      determine the effect of [6]-gingerol on TPA-induced activation of NF-kappaB.
      Pretreatment with [6]-gingerol resulted in a decrease in both TPA-induced DNA
      binding and transcriptional activities of NF-kappaB through suppression of
      IkappaBalpha degradation and p65 nuclear translocation. Phosphorylation of both
      IkappaBalpha and p65 was substantially blocked by [6]-gingerol. In addition, [6]
      gingerol inhibited TPA-stimulated interaction of phospho-p65-(Ser-536) with cAMP
      response element binding protein-binding protein, a transcriptional coactivator
      of NF-kappaB. Moreover, [6]-gingerol prevented TPA-induced phosphorylation and
      catalytic activity of p38 mitogen-activated protein (MAP) kinase that regulates
      COX-2 expression in mouse skin. The p38 MAP kinase inhibitor SB203580 attenuated
      NF-kappaB activation and subsequent COX-2 induction in TPA-treated mouse skin.
      Taken together, our data suggest that [6]-gingerol inhibits TPA-induced COX-2
      expression in mouse skin in vivo by blocking the p38 MAP kinase-NF-kappaB
      signaling pathway.

PMID- 15735739
TI  - TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage.
AB  - Inactivation of the BRCA1 gene has been found to confer susceptibility to early
      onset familial breast and ovarian cancers. BRCA1 regulates DNA repair, chromatin
      remodeling and affects gene transcription. Transforming growth factor-beta
      (TGFbeta) is a potent regulator of growth, apoptosis and invasiveness of tumor
      cells, including breast cancer cells. Here we show that Smad3 which is a
      component of the TGFbeta signaling pathway, forms a complex with BRCA1 in vitro
      and in vivo. The interaction is mediated by the MH1 domain of Smad3 and the C
      terminal part of BRCA1. We observed a co-localization of Smad3 and BRCA1 in
      nuclear complexes. We also found that TGFbeta1/Smad3 counteracted BRCA1-dependent
      repair of DNA double-strand breaks in human breast epithelial cells, as evaluated
      by BRCA1 nuclear foci formation, single-cell gel electrophoresis and cell
      survival assays. Thus, TGFbeta1/Smad3 suppresses BRCA1-dependent DNA repair in
      response to a DNA damaging agent.

PMID- 15735740
TI  - Expression of a constitutively active mutant of M-Ras in normal bone marrow is
      sufficient for induction of a malignant mastocytosis/mast cell leukemia, distinct
      from the histiocytosis/monocytic leukemia induced by expression of activated H
      Ras.
AB  - Expression of constitutively activated M-Ras in normal murine bone-marrow cells
      was sufficient to induce the factor-independent, in vitro growth and
      differentiation of colonies of macrophages and neutrophils, and the generation of
      immortal lines of factor-independent mast cells, and, upon in vivo injection of
      the transduced cells, a fatal mastocytosis/mast-cell leukemia. In contrast,
      expression of constitutively activated H-Ras in bone-marrow cells resulted in the
      in vitro growth, in the absence of exogenous factors, of colonies that contained
      only macrophages and of lines of cells resembling dendritic cells, and, upon in
      vivo injection of the transduced cells, a fatal histiocytosis/monocytic leukemia.
      Macrophages generated by bone-marrow cells expressing activated M-Ras or
      activated H-Ras differed morphologically, the latter appearing more activated, a
      difference abrogated by an inhibitor of Erk activation. Inhibition of either Erk
      or PI3 kinase blocked the capacity of both activated M-Ras and activated H-Ras to
      support proliferation and viability. However, inhibition of p38 MAPK activity
      suppressed proliferation of bone-marrow cells expressing activated H-Ras, but
      enhanced that of bone-marrow cells expressing activated M-Ras. Thus, expression
      of either activated M-Ras or H-Ras in normal hematopoietic cells was sufficient
      for transformation but each resulted in the generation of distinct lineages of
      cells.

PMID- 15735741
TI  - DIM stimulates IFNgamma gene expression in human breast cancer cells via the
      specific activation of JNK and p38 pathways.
AB  - 3,3'-Diindolylmethane (DIM) is a promising anticancer agent derived from Brassica
      vegetables, but the mechanisms of DIM action are largely unknown. We have shown
      that DIM can upregulate the expression and stimulate the secretion of interferon
      gamma (IFNgamma) in the human MCF-7 breast cancer cell line. This novel effect
      may provide important clues to explain the anticancer effects of DIM because it
      is well known that IFNgamma plays an important role in preventing the development
      of primary and transplanted tumors. Utilizing promoter deletions, we show here
      that the region between -108 and -36 bp in the IFNgamma promoter, which contains
      two conserved and essential regulatory elements, is required for DIM-induced
      IFNgamma expression. DIM activates both JNK and p38 pathways, induces the
      phosphorylation of c-Jun and ATF-2, and increases the binding of the homodimer or
      heterodimer of c-Jun/ATF-2 to the proximal AP-1.CREB-ATF-binding element.
      Moreover, studies with specific enzyme inhibitors showed that up-stream Ca2+
      dependent kinase(s) is required for the inducing effects of DIM in MCF-7 cells.
      These results establish that DIM-induced IFNgamma expression in human breast
      tumor cells is mediated by activation of both JNK and p38 pathways, which is
      ultimately dependent on intracellular calcium signaling.

PMID- 15735743
TI  - Constitutive activation of the Wnt/beta-catenin signalling pathway in acute
      myeloid leukaemia.
AB  - The beta-catenin protein is at the core of the canonical Wnt signalling pathway.
      Wnt stimulation leads to beta-catenin accumulation, nuclear translocation and
      interaction with T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription
      factors to regulate genes important for embryonic development and proliferation.
      Wnt/beta-catenin can promote stem cell self-renewal and is dysregulated in colon
      carcinoma. We have examined the role of the Wnt pathway in the development of
      acute myeloid leukaemia (AML) and find that the beta-catenin protein is readily
      detected in primary AML samples. Using transfection of a TCF/LEF reporter
      construct into primary AML cells and normal human progenitors, we find increased
      reporter activity in 16/25 leukaemia samples. Retrovirally mediated expression of
      a mutant active beta-catenin in normal progenitors preserves CD34 expression and
      impairs myelomonocytic differentiation. Activation of TCF/LEF signalling
      decreases factor withdrawal-induced apoptosis of normal progenitors. A
      significant proportion of AML cases show aberrant expression of components of the
      Wnt pathway including Wnt-1, Wnt-2b and LEF-1. These results provide evidence for
      the involvement of the Wnt/beta-catenin pathway in the pathogenesis of AML.

PMID- 15735742
TI  - Caspase-8L expression protects CD34+ hematopoietic progenitor cells and leukemic
      cells from CD95-mediated apoptosis.
AB  - Regulation of sensitivity or resistance for apoptosis by death receptor ligand
      systems is a key control mechanism in the hematopoietic system. Dysfunctional or
      deregulated apoptosis can potentially contribute to the development of immune
      deficiencies, autoimmune diseases, and leukemia. Control of homeostasis starts at
      the level of hematopoietic stem cells (HSC). To this end, we found that CD34+
      hematopoietic progenitor cells are constitutively resistant to CD95-mediated
      apoptosis and cannot be sensitized during short-term culture to death receptor
      mediated apoptosis by cytokines. Detailed analysis of the death machinery
      revealed that CD34+ cells do not express caspase-8a/b, a crucial constituent of
      the death-inducing signaling complex (DISC) of death receptors. Instead, we found
      a smaller splice variant termed caspase-8L to be present in HSC. Forced
      expression of caspase-8L using a recombinant lentiviral vector was able to
      protect hematopoietic cells from death receptor-induced apoptosis even in the
      presence of caspase-8a/b. Furthermore, we found that caspase-8L is recruited to
      the DISC after CD95 triggering, thereby preventing CD95 from connecting to the
      caspase cascade. These results demonstrate an antiapoptotic function of caspase
      8L and suggest a critical role as apoptosis regulator in HSC. Similar to CD34+
      HSC, stem cell-derived leukemic blasts from AML(M0) patients only expressed
      caspase-8L. Additionally we found, caspase-8L expression in several AML and ALL
      samples. Thus, caspase-8L expression might explain constitutive resistance to
      CD95-mediated apoptosis in CD34+ progenitor cells and might participate in the
      development of stem cell-derived and other leukemias by providing protection from
      regulatory apoptosis.

PMID- 15735744
TI  - Differential modulation of malignant peripheral nerve sheath tumor growth by
      omega-3 and omega-6 fatty acids.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder of the nervous system
      resulting in neurofibromas and malignant peripheral nerve sheath tumors (MPNST).
      In this study, we report the modulation of murine and human MPNST cell growth by
      the fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA
      demonstrated a tendency to stimulate cell growth at low doses and induce
      apoptosis at high doses, paralleled by the activation of ERK and caspase-3.
      Furthermore, high-dose DHA reversed the stimulation of MPNST cell growth by a
      number of growth factors suggested to have a pathogenic effect in NF1 and
      inhibited MPNST growth in vivo. AA was found to have a reciprocal activity in
      vitro, stimulating MPNST cell growth at comparable concentrations and reducing
      DHA activation of ERK. These findings introduce fatty acids as a possible
      regulator of MPNST development in NF1 patients.

PMID- 15735745
TI  - PRIMA-1(MET) synergizes with cisplatin to induce tumor cell apoptosis.
AB  - Mutant p53-carrying tumors are often more resistant to chemotherapeutical drugs.
      We demonstrate here that the mutant p53-reactivating compound PRIMA-1(MET) acts
      synergistically with several chemotherapeutic drugs to inhibit tumor cell growth.
      Combined treatment with cisplatin and PRIMA-1(MET) resulted in a synergistic
      induction of tumor cell apoptosis and inhibition of human tumor xenograft growth
      in vivo in SCID mice. The induction of mutant p53 levels by chemotherapeutic
      drugs is likely to increase the sensitivity of tumor cells to PRIMA-1(MET). Thus,
      the combination of PRIMA-1(MET) with currently used chemotherapeutic drugs may
      represent a novel and more efficient therapeutic strategy for treatment of mutant
      p53-carrying tumors.

PMID- 15735746
TI  - Overexpression of human beta TrCP1 deleted of its F box induces tumorigenesis in
      transgenic mice.
AB  - Genetic alterations affecting beta-catenin, adenomatous polyposis coli or axin
      proteins are associated with the pathogenesis of numerous human tumors. All these
      mutations result in the synthesis of unphosphorylated beta-catenin that escapes
      recognition by the beta transducin repeat protein (beta TrCP1), the receptor of
      an ubiquitin. The stabilized beta-catenin translocates to the nucleus and
      activates the transcription of genes crucial for tumorigenesis. Recent evidence
      implicates mutations and overexpresssion of beta TrCP1 in human prostate and
      colon tumors, respectively, suggesting that deregulated beta TrCP1 may be
      involved in tumorigenesis. To explore this possibility further, we generated
      transgenic mice that specifically express a dominant-negative mutant of beta
      TrCP1 (Delta F beta TrCP1) or full-length beta TrCP1 in intestine, liver and
      kidney. We found that 46% (16/35) of the transgenic mice that overexpressed the
      transgenes developed either intestinal adenomas (10/35) or hepatic (4/35) or
      urothelial (2/35) tumors. Immunohistological analysis of the tumors revealed that
      upregulation of cyclin D1, glutamine synthetase and chemotaxin 2 was associated
      with nuclear accumulation of beta-catenin. These results show that the
      overexpression of Delta F beta TrCP1 or beta TrCP1 in vivo induce tumors through
      beta-catenin activation.

PMID- 15735747
TI  - Functional consequences of G alpha 13 mutations that disrupt interaction with
      p115RhoGEF.
AB  - The G-protein alpha subunit, alpha(13), regulates cell growth and differentiation
      through the monomeric Rho GTPase. Alpha(13) activates Rho through direct
      stimulation of the guanine nucleotide exchange factor p115RhoGEF, which contains
      a regulator of G-protein signaling homology domain (RH) in its N-terminus.
      Through its RH domain, p115RhoGEF also functions as a GAP for G alpha(13). The
      mechanism for the G alpha(13)/p115RhoGEF interaction is not well understood.
      Here, we determined specific alpha(13) residues important for its interaction
      with p115RhoGEF. GST-pulldowns and co-immunoprecipitation assays revealed that
      individually mutating alpha(13) residues Lys204, Glu229, or Arg232 to opposite
      charge residues disrupts the interaction of activated alpha(13) with the RH
      domain of p115RhoGEF or full-length p115RhoGEF. We further demonstrate that
      mutation of Glu229, and to a lesser extent Lys204 or Arg232, disrupts the ability
      of activated alpha(13) to induce the recruitment of p115RhoGEF to the plasma
      membrane (PM) and to activate Rho-mediated serum response element-luciferase gene
      transcription. Interestingly, an alpha(13) mutant where a conserved Gly was
      mutated to a Ser (G205S) retained its ability to bind to p115RhoGEF, induce
      p115RhoGEF recruitment to the PM, and activate Rho-dependent signaling, even
      though identical Gly to Ser mutations in other alpha disrupt their interaction
      with regulator of G-protein signaling (RGS) proteins. These results demonstrate
      that, whereas several features of a typical alpha/RGS interaction are preserved
      in the alpha(13)/p115RhoGEF interaction, there are also significant differences.

PMID- 15735748
TI  - Chronic gastritis in the hypochlorhydric gastrin-deficient mouse progresses to
      adenocarcinoma.
AB  - The current study tests the hypothesis that chronic atrophic gastritis from
      hypochlorhydria in the gastrin-deficient mouse predisposes the stomach to gastric
      cancer. Gross morphology and histology of 12-month-old wild-type (WT), gastrin
      deficient (G-/-) and somatostatin-deficient (SOM-/-) mice were examined. Parietal
      and G cells, Ki67, TUNEL, villin and MUC2 expression were analysed by
      immunohistochemistry. RUNX3 and STAT3 expression was analysed by Western blot.
      Anchorage-independent growth was determined by cell cluster formation in soft
      agar. Compared to the WT and SOM-/- mice, hypochlorhydric G-/- mice developed
      parietal cell atrophy, significant antral inflammation and intestinal metaplasia.
      Areas of metaplasia within the G-/- mouse stomach showed decreased RUNX3
      expression with elevated MUC2 and villin expression. Cells isolated from the
      tumor grew in soft agar. However, the cells isolated from WT, nontransformed G-/-
      and SOM-/- gastric tissue did not form colonies in soft agar. Consistent with
      elevated antral proliferation, tumor tissue isolated from the G-/- mice showed
      elevated phosphorylated STAT3 expression. We then examined the mechanism by which
      STAT3 was constitutively expressed in the tumor tissue of the G-/- mice. We found
      that IFNgamma expression was also significantly higher in the tumor tissue of G-/
      mice compared to WT and SOM-/- animals. To determine whether STAT3 was regulated
      by IFNgamma, MKN45 cells were cocultured with IFNgamma or gastrin. IFNgamma
      significantly stimulated phosphorylation of STAT3 in the MKN45 cell line, but not
      gastrin. Therefore, we show here that in the hypochlorhydric mouse stomach, the
      chronic gastritis, atrophy, metaplasia, dysplasia paradigm can be recapitulated
      in mice. Moreover, neoplastic transformation of the antral gastric mucosa does
      not require gastrin.

PMID- 15735749
TI  - Mesenchymal cells generated from patients with myelodysplastic syndromes are
      devoid of chromosomal clonal markers and support short- and long-term
      hematopoiesis in vitro.
AB  - Myelodysplastic syndromes (MDS) are clonal malignant stem cell disorders
      characterized by inefficient hematopoiesis. The role of the marrow
      microenvironment in the pathogenesis of the disease has been controversial and no
      study has been performed so far to characterize mesenchymal cells (MC) from MDS
      patients and to analyse their ability to support hematopoiesis. To this end, we
      have isolated and characterized MC at diagnostic marrow samples (n=12) and have
      purified their CD34+CD38- and CD34+CD38+ counterparts (n=7) before using MC as a
      short- and long-term hematopoietic support. We show that MC can be readily
      isolated from MDS marrow and exhibit a major expansion potential as well as an
      intact osteoblastic differentiation ability. They do not harbor the abnormal
      marker identified by FISH in the hematopoietic cells and they stimulate the
      growth of autologous clonogenic cells. Conversely, highly purified stem cells and
      their cytokine-expanded progeny harbor the clonal marker with variable
      frequencies, and both normal and abnormal long-term culture-initiating cell
      derived progeny can be effectively supported by autologous MC. Thus, we
      demonstrate that MDS marrow is an abundant source of MC appearing both
      cytogenetically and functionally noninvolved by the malignant process and able to
      support hematopoiesis, suggesting their possible usefulness in future cell
      therapy approaches.

PMID- 15735750
TI  - TRAIL is a key target in S-phase slowing-dependent apoptosis induced by
      interferon-beta in cervical carcinoma cells.
AB  - Interferon (IFN)-beta induces S-phase slowing and apoptosis in human papilloma
      virus (HPV)-positive cervical carcinoma cell line ME-180. Here, we show that
      apoptosis is a consequence of the S-phase lengthening imposed by IFN-beta,
      demonstrating the functional correlation between S-phase alteration and apoptosis
      induction. In ME-180 cells, where p53 function is inhibited by HPV E6
      oncoprotein, IFN-beta effects on cell cycle and apoptosis occur independently of
      p53. The apoptosis due to IFN-beta is mediated by the tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) in a manner dependent on the S-phase
      deregulation. IFN-beta appears to increase TRAIL expression both directly at the
      mRNA level and indirectly by augmenting surface protein levels as a consequence
      of the induced S-phase cell accumulation. Moreover, the alteration of the S-phase
      due to IFN-beta promotes TRAIL-dependent apoptosis by potentiating cell
      sensitivity to TRAIL, possibly through induction of a proapoptotic NF-kappaB
      activity and TRAIL-R2 receptor expression. Interestingly, IFN-beta-induced TRAIL
      dependent apoptotic events strongly differ in the requirement of caspase
      activity. These results show that IFN-beta may induce an apoptotic response by
      deregulating cell cycle. Understanding the linkage between these mechanisms
      appears to be of primary importance in the search for new IFN-based therapeutic
      strategies to circumvent cancer disease or improve clinical outcome.

PMID- 15735751
TI  - Sequential 5-Aza 2'-deoxycytidine/depsipeptide FK228 treatment induces tissue
      factor pathway inhibitor 2 (TFPI-2) expression in cancer cells.
AB  - cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer
      cells mediated by sequential 5-aza 2'-deoxycytidine (DAC)/depsipeptide FK228 (DP)
      exposure in order to identify translational end points for clinical trials
      evaluating these agents. In both cell lines, sequential DAC/DP treatment induced
      expression of tissue factor pathway inhibitor-2 (TFPI-2), an inhibitor of Factor
      VII: tissue factor signal transduction known to diminish the malignant phenotype
      of cancer cells. TFPI-2 expression was diminished or absent in 16 of 32 cell
      lines established from thoracic malignancies. Sequential DAC/DP treatment induced
      TFPI-2 in cancer cells deficient for TFPI-2 expression in the basal state.
      Promoter methylation coincided with loss of TFPI-2 expression in a number of
      cancer lines. TFPI-2 promoter methylation was observed in one of five pulmonary
      adenocarcinomas, and seven of seven esophageal adenocarcinomas, but not
      corresponding normal tissues. DP enhanced acetylation of TFPI-2-associated
      histones in CALU-6 cells. DP or PDBU, alone, induced TFPI-2 expression in cancer
      cells deficient for TFPI-2 expression in the absence of promoter methylation. In
      these cells, DP-mediated TFPI-2 induction was abrogated by calphostin. Induction
      of TFPI-2 by distinct, yet cooperative mechanisms involving chromatin remodeling
      and PKC signaling strengthens the preclinical rationale for sequential
      administration of DNA demethylating agents and HDAC inhibitors in cancer
      patients. Furthermore, induction of TFPI-2 may be a useful surrogate marker of
      treatment response in individuals receiving sequential DAC/DP infusions.

PMID- 15735752
TI  - E2F suppression and Sp1 overexpression are sufficient to induce the
      differentiation-specific marker, transglutaminase type 1, in a squamous cell
      carcinoma cell line.
AB  - Recently, E2F function has expanded to include the regulation of differentiation
      in human epidermal keratinocytes (HEKs). We extend these findings to report that
      in HEKs, Sp1 is a differentiation-specific activator and a downstream target of
      E2F-mediated suppression of the differentiation-specific marker, transglutaminase
      type 1 (TG-1). Deletion of elements between -0.084 to -0.034 kb of the TG-1
      promoter disabled E2F1-induced suppression of promoter activity. Electrophoretic
      mobility shift assays (EMSAs) demonstrated that Sp1 and Sp3 bound this region.
      Protein expression analysis suggested that squamous differentiation was
      accompanied by increased Sp1/Sp3 ratio. Cotransfection of proliferating HEKs or
      the squamous cell carcinoma (SCC) cell line, KJD-1/SV40, with an E2F inhibitor
      (E2Fd/n) and Sp1 expression plasmid was sufficient to activate the TG-1 promoter.
      The suppression of Sp1 activity by E2F in differentiated cells appeared to be
      indirect since we found no evidence of an Sp1/E2F coassociation on the TG-1
      promoter fragment. Moreover, E2F inhibition in the presence of a differentiation
      stimulus induced Sp1 protein. These data demonstrate that (i) Sp1 can act as a
      differentiation stimulus, (ii) E2F-mediated suppression of differentiation
      specific markers is indirect via Sp1 inhibition and (iii) a combination of E2F
      inhibition and Sp1 activation could form the basis of a differentiation therapy
      for SCCs.

PMID- 15735753
TI  - Epigenetic inactivation of the human sprouty2 (hSPRY2) homologue in prostate
      cancer.
AB  - Abnormal signalling events mediated by receptor tyrosine kinases (RTKs)
      contribute to human carcinogenesis. Sprouty2 (Spry2) is a key antagonistic
      regulator of RTK signalling and suppression of its expression or function may
      facilitate proliferation and angiogenesis. Using prostate cancer (CaP) as a
      model, we investigated the significance of Spry2 in human malignancy. We observed
      downregulated Spry2 expression in invasive CaP cell lines and high-grade clinical
      CaP (compared to benign prostatic hyperplasia (BPH) and well-differentiated
      tumours, P=0.041). A large CpG island is associated with hSPRY2, and extensive
      hypermethylation of this CpG island was observed in 76-82% of high-grade CaP,
      while control BPH tissues were predominantly unmethylated (P=0.0005).
      Furthermore, suppressed Spry2 expression correlated with methylation of the CpG
      region in clinical samples (P=0.004) and treatment with 5-aza-2'-deoxycytidine
      reactivated Spry2 expression in LNCaP and PC-3M cells. hSPRY2 maps to the long
      arm of chromosome 13 (13q31.1), where loss of heterozygosity (LOH) has been
      reported. We found no evidence of mutation; however, we demonstrated 27-40% LOH
      using flanking markers to hSPRY2. Hence, while biallelic epigenetic inactivation
      of hSPRY2 represents the main genetic event in prostate carcinogenesis, the
      observed 27-40% LOH presents evidence of hemizygous deletion with the remaining
      allele hypermethylated. We therefore propose hSPRY2 as a potential tumour
      suppressor locus in CaP.

PMID- 15735754
TI  - Wnt-5a has tumor suppressor activity in thyroid carcinoma.
AB  - Stabilization of beta-catenin by inhibition of its phosphorylation is
      characteristic of an activation of the canonical Wnt/beta-catenin signaling
      pathway and is associated with various human carcinomas. It contrasts to an as
      yet incompletely characterized action of an alternative noncanonical Wnt
      signaling pathway on neoplastic transformation. The aim of the present study was
      to test the effects of a member of the noncanonical Wnt signaling pathway, Wnt
      5a, in primary thyroid carcinomas and in thyroid carcinoma cell lines. Compared
      to normal tissue Wnt-5a mRNA expression was clearly increased in thyroid
      carcinomas. Immunohistochemically, a bell-shaped response was observed with low
      to undetectable levels in normal tissue and in anaplastic tumors whereas
      differentiated thyroid carcinomas showed strong positive immunostaining for Wnt
      5a. Transfection of Wnt-5a in a thyroid tumor cell line FTC-133 was able to
      reduce proliferation, migration, invasiveness and clonogenicity in these cells.
      These effects of Wnt-5a are associated with membranous beta-catenin translocation
      and c-myc oncogene suppression and are mediated through an increase in
      intracellular Ca(2+) release, which via CaMKII pathways promotes beta-catenin
      phosphorylation. Specific inhibition of beta-catenin phosphorylation by W-7, a
      calmodulin inhibitor, or by KN-93, a CaMKII inhibitor, supports these findings
      whereas PKC inhibitors were without effect. This interaction occurs downstream of
      GSK-3 beta as no Wnt-5a effect was seen on the Ser(9) phosphorylation of GSK-3
      beta. Our data are compatible with the hypothesis that Wnt-5a serves as an
      antagonist to the canonical Wnt-signaling pathway with tumor suppressor activity
      in differentiated thyroid carcinomas.

PMID- 15735755
TI  - PML interacts with Myc, and Myc target gene expression is altered in PML-null
      fibroblasts.
AB  - c-myc is a well-known proto-oncogene encoding for a transcription factor that
      needs to be tightly regulated in order to preserve cell homeostasis. The
      Promyelocytic Leukaemia gene product PML plays an important role in cell growth
      and survival, and resides in discrete subnuclear structures called Nuclear Bodies
      (NB). We performed comparative analysis of the expression of 40 Myc target genes
      and of Myc binding to their regulatory regions both in wild-type and PML knockout
      cells. We demonstrate that if PML is absent, despite Myc binding to the DNA
      regulatory sequences is unchanged, the expression profile of several Myc target
      genes is altered. PML is largely involved in gene regulation, via recruitment of
      several transcription factors and cofactors to the NB. Consistently, we show that
      Myc partially localizes to the NB and physically interacts with PML, and that
      this localization depends on Myc expression levels. As deregulation occurs to
      both activated and repressed Myc target genes, we propose that PML influences Myc
      transcriptional activity through a mechanism that involves the control of Myc
      post-translational modifications.

PMID- 15735756
TI  - Phosphorylation of cyclin D1 at Thr 286 during S phase leads to its proteasomal
      degradation and allows efficient DNA synthesis.
AB  - Continuing proliferation requires regulation of cyclin D1 levels in each cell
      cycle phase. Growth factors stimulate high levels during G2 phase, which commits
      the cell to continue through G1 phase with sufficient cyclin D1 to initiate DNA
      synthesis. Upon entry into S phase, however, cyclin D1 levels rapidly decline.
      Our goal is to understand the mechanism and importance of this S-phase
      suppression. Here, we demonstrate that cyclin D1 levels decline during S phase
      due to reduced protein stability, without alterations in the rate of protein
      synthesis. This decline depends upon Thr 286, since mutation of this site
      eliminates the normal pattern of cyclin D1 suppression during S phase. As
      evidence that phosphorylation of Thr 286 is responsible for this decline, Thr 286
      is shown to be more efficiently phosphorylated during S phase than in other cell
      cycle periods. Finally, high cyclin D1 levels during S phase are shown to inhibit
      DNA synthesis. This inhibitory activity presumably blocks the growth of cells
      with altered cyclin D1 expression characteristics. Abnormal stimulation of cyclin
      D1 might result in levels high enough to promote G1/S phase transition even in
      the absence of appropriate growth stimuli. In such cells, however, the levels of
      cyclin D1 would presumably be too high to be suppressed during S phase, resulting
      in the inhibition of DNA synthesis.

PMID- 15735757
TI  - Inactivated MGMT by O6-benzylguanine is associated with prolonged G2/M arrest in
      cancer cells treated with BCNU.
AB  - HCT116 and HCT15 cells that highly express O(6)-methylguanine-DNA
      methyltransferase (MGMT) displayed a transient cell cycle G2/M arrest in response
      to exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) alone; however, 70-80%
      of cells were arrested in G2/M after treatment with O(6)-benzylguanine (BG) and
      BCNU. Cells accumulated in G2/M showed elevated levels of an inactive form of
      cyclin B1/p-Cdc2 (Tyr15) complex that was not associated with activation of
      Chk1/p-Cdc25C and was independent of p53/p21 status. The most prominent feature
      of cell death was the appearance of enlarged and multinucleated cells that was
      related to the inhibition of mitotic entry. In contrast, BG-resistant cell lines,
      HCT116 BBR and HCT15 BBR cells that contain mutations K165E and K165N of MGMT,
      respectively, displayed a normal cell cycle progression with a slight and
      transient increase in G2/M arrest at 24 h after treatments with either BCNU alone
      or BG combined with BCNU. The differences in the ability to progress toward G2/M
      after treatment with BG and BCNU between cells expressing wild-type MGMT and
      mutated MGMT were confirmed in CHO cells transfected with human wild type and
      K165E mutant MGMT cDNA, respectively. Thus, our findings suggest that BG
      inactivated MGMT may be linked to cell signaling events, forcing cells into a
      permanent G2/M arrest in response to the DNA damages induced by BCNU.

PMID- 15735758
TI  - p53 deficiency exacerbates pleiotropic mitotic defects, changes in nuclearity and
      polyploidy in transdifferentiating pancreatic acinar cells.
AB  - In a primary culture model for pancreatic acinar-ductal transdifferentiation,
      cells exhibited increased proliferation, changes in nuclearity and polyploidy. We
      identify the 'nucleus to centrosome' ratio of the progenitor cell, the
      dissemination of centrosomes at spindle poles and cytokinesis failure as critical
      determinants of mitosis outcome and centrosome inheritance. Abortive cytokinesis
      of mononuclear cells contributes to the binuclear cell pool, whereas enclosure of
      entire mitotic formations, within a single nuclear envelope, perpetuates
      polyploidization. Binuclear cell nuclei combine their genomes on a single
      metaphase plate, doubling descendant ploidy. Moreover, approximately 42% of
      binuclear and tetraploid cells assemble aberrant spindles with up to 8
      centrosomes/poles. These phenotypes were exacerbated in p53-deficient cultures
      exhibiting increased S-phase entry, giant nuclei, multinucleation, multipolar
      mitoses and centrosome hyperamplification. The tendency of p53-proficient cells
      to spontaneously evade the tetraploidy checkpoint degenerates to uncontrolled
      polyploid progression in p53-deficient cultures, explaining why p53 abrogation
      alone rapidly descends to aneuploidy in this system. We detected constitutively
      nuclear mdm2, which may circumvent endogenous cell-cycle checkpoints, and
      pronounced accumulation of p21 and p27 in multinuclear cells and giant nuclei,
      consistent with roles in polyploidization. This in vitro model may recapitulate
      the processes underlying genomic instability in pancreatic tumours in vivo, and
      attests to the existence of a p53-dependent polyploidy checkpoint acting to limit
      the degree of polyploidization.

PMID- 15735759
TI  - Expression and function of vascular endothelial growth factor receptor-1 on human
      colorectal cancer cells.
AB  - Vascular endothelial growth factor (VEGF) is associated with tumor angiogenesis
      and poor prognosis in human colorectal cancer (CRC). VEGF receptor-1 (VEGFR-1 or
      Flt-1) is a high-affinity receptor for VEGF and is typically considered specific
      to endothelial cells. Here we report the expression and function of VEGFR-1 in
      CRC cell lines. VEGFR-1 was expressed in all CRC cell lines studied as determined
      by RT-PCR, Western blot analysis, FACS, and ELISA. Treatment of the human CRC
      cell lines HT-29 and SW480 with VEGF-A (a ligand for both VEGFR-1 and -2) or VEGF
      B (a ligand specific for VEGFR-1) led to activation of Erk-1/2, SAPK/JNK, and
      translocation of the p65 subunit of nuclear factor-kappaB into the nucleus. Both
      VEGF-A and -B led to significant induction of cell motility and invasiveness of
      CRC cells. Stimulation of cells with VEGF-A or -B also led to larger and more
      numerous colonies in soft agar. However, activation of VEGFR-1 did not increase
      CRC cell proliferation. In contrast to the previous paradigm that VEGFRs are not
      present on tumor cells of epithelial origin, we found that VEGFR-1 is present and
      functional on CRC cells, and activation by VEGF family ligands can activate
      processes involved in tumor progression and metastasis.

PMID- 15735760
TI  - A role for Ubc9 in tumorigenesis.
AB  - The post-translational modifications ubiquitination and sumoylation have been
      implicated in regulating many critical cellular pathways. Like ubiquitination,
      sumoylation is a multistep process involving maturation, activation, conjugation
      and deconjugation. Ubc9 is a sole E2-conjugating enzyme essential for
      sumoylation. We have previously shown that alterations of Ubc9 expression affect
      tumor drug responsiveness. However, it is not clear whether there is any link
      between sumoylation and tumorigenesis, even though alterations of the
      ubiquitination pathway can lead to the development of cancer. In this study, we
      found that Ubc9 expression levels were elevated in ovarian tumors compared to the
      matched normal ovarian specimens, suggesting that Ubc9 may play a role in
      tumorigenesis. To test this, we overexpressed a dominant-negative mutant of Ubc9
      (Ubc9-DN) and wild-type Ubc9 (Ubc9-WT) in the MCF-7 human breast tumor cells.
      Inoculating these cells as xenografts in mice revealed that tumors expressing
      Ubc9-WT grew better than the vector control, while tumors expressing Ubc9-DN
      exhibited reduced growth. This pattern was also seen in these cells when grown in
      culture. To better understand the mechanism behind this observation, we profiled
      gene expressions in these cells by microarray analysis and found alterations in
      expression of the pro-oncogene bcl-2 in these Ubc9-DN- and Ubc9-WT-expressing
      cells. Consistent with the bcl-2 results, subsequent studies revealed a higher
      rate of apoptosis and poor survival for the MCF-7 cells expressing Ubc9-DN, which
      are associated with downregulation of bcl-2. Together, these results suggest a
      role for Ubc9 in tumorigenesis at least partially through regulation of bcl-2
      expression.

PMID- 15735761
TI  - Tweak induces mammary epithelial branching morphogenesis.
AB  - Members of the tumor necrosis factor (TNF) superfamily regulate cell survival and
      proliferation and have been implicated in cancer. Tweak (TNF-related weak inducer
      of apoptosis) has pleiotropic biological functions including proapoptotic,
      proangiogenic and proinflammatory activities. We explored a role for Tweak in
      mammary gland transformation using a three-dimensional model culture system.
      Tweak stimulates a branching morphogenic phenotype, similar to that induced by
      pro-oncogenic factors, in Eph4 mammary epithelial cells cultured in matrigel.
      Increased proliferation and invasiveness are observed, with a concomitant
      inhibition of functional differentiation. Levels of matrix metalloproteinase-9
      (MMP-9) are significantly increased following Tweak treatment. Notably, MMP
      inhibitors are sufficient to block the branching phenotype induced by Tweak. The
      capacity to promote proliferation, inhibit differentiation and induce invasion
      suggests a role for Tweak in mammary gland tumorigenesis. Consistent with this,
      we have observed elevated protein levels of the Tweak receptor, Fn14, in human
      breast tumor cell lines and xenograft models as well as in primary human breast
      tumors. Together, our results suggest that the Tweak/Fn14 pathway may be
      protumorigenic in human breast cancer.

PMID- 15735762
TI  - Induction of human metallothionein 1G promoter by VEGF and heavy metals:
      differential involvement of E2F and metal transcription factors.
AB  - The E2F transcription factors induce the expression of many genes in response to
      specific extracellular stimuli. Here, we show that human metallothionein 1G
      (hMT1G) promoter is upregulated by E2F1 upon VEGF stimulation of human aortic
      endothelial cells. Analysis of the hMT1G promoter showed the presence of many
      potential E2F-binding sites flanked by potential SP1 sites and metal response
      elements (MREs). hMT1G promoter could be induced by E2F1 in transient
      transfections; further, deletion analysis suggested that the region spanning the
      E2F-binding sites was necessary for VEGF-mediated induction. E2Fs 1-5 could bind
      to the hMT1G promoter in a chromatin immunoprecipitation assay. VEGF stimulation
      led to an increased binding of E2Fs 1-3 to the endogenous hMT1G promoter; at the
      same time, the binding of Rb, p107 and p130 to the promoter was abolished. VEGF
      stimulation also led to the increased acetylation E2F1 as well as the histones in
      the hMT1G promoter region. Stimulation with metals or VEGF led to dissociation of
      histone deacetylase 1 (HDAC1) from the promoter, leading to acetylation of
      histones. Induction of the hMT1G promoter upon exposure to heavy metals such as
      Zn and Cd is mediated by the MRE. Interestingly, mutation of MRE affected the
      metal response, but not the VEGF response of the hMT1G promoter. In contrast,
      deletion of the E2F-binding sites did not affect the metal response. Based on
      these findings, we conclude that induction of the hMT1G promoter by VEGF and
      heavy metals occurs through the utilization of different transcription factors.

PMID- 15735763
TI  - MBD2 deficiency does not accelerate p53 mediated lymphomagenesis.
AB  - Recent studies using hypomorphic DNA methyltransferase 1 (DNMT1) alleles have
      suggested that strategies aiming to reduce DNA methylation may increase genomic
      instability and lymphomagenesis. Given our recent finding that loss of methyl
      binding domain protein 2 (Mbd2) suppresses intestinal tumorigenesis, we have
      tested whether loss of Mbd2 increases lymphomagenesis by intercrossing Mbd2
      deficient mice with p53 deficient and p53 heterozygous mice. Unlike DNMT1, loss
      of Mbd2 does not accelerate lymphomagenesis, arguing that MBD2 may represent a
      better potential therapeutic target than DNMT1.

PMID- 15735764
TI  - Identification of a novel nucleolar localization signal and a degradation signal
      in Survivin-deltaEx3: a potential link between nucleolus and protein degradation.
AB  - For a long time, as the most prominent subnuclear structure, nucleolus has been
      recognized as a main site where rRNA processing and ribosomal subunit assemblies
      take place. It has not been until recently that additional functions of nucleolus
      have begun to be proposed. In this study, we for the first time demonstrate that
      Survivin-deltaEx3, a novel functionally splice variant of Survivin localizes in
      the nucleoli where it degrades rapidly through ubiquitin-proteosome pathway.
      Several lines of evidences provided in this report support this finding (i) a
      novel nucleolar localization sequence (NoLS, MQRKPTIRRKNLRLRRK) and a novel
      degradation signal (aa92-aa137) within Survivin-deltaEx3 were identified (ii)
      proteasome inhibitors MG132 or ALLN greatly inhibits degradation of Survivin
      deltaEx3 and polyubiquitination of Survivin-deltaEx3 was detected (iii)
      heterologous proteins such as TAT-PTD or p14ARF, when fused to this putative
      degradation signal, result in a significant degradation within the nucleolus. In
      addition, the nucleolar localization and degradation of Survivin-deltaEx3 appear
      to be required for its antiapoptotic function, since neither NoLS-deleted nor
      degradation signal-deleted Survivin-deltaEx3 retains protective effect against
      Doxorubicin-induced apoptosis. Thus, our results have provided evidences to
      suggest that besides cytosol, nucleus, endoplsmic reticulum (ER) or lysosomes,
      nucleolus may also operate important protein degradation pathway, which has been
      overlooked previously.

PMID- 15735767
TI  - [Is leadership in surgery--a value in danger?].

PMID- 15735765
TI  - The 3p21 candidate tumor suppressor gene BAF180 is normally expressed in human
      lung cancer.
AB  - BAF180 encoding a subunit of the human SWI/SNF chromatin remodeling complex maps
      to 3p21, in a region where frequent allele loss has been detected in lung cancer.
      BAF180 can be mutated and has tumor suppressing properties in breast cancer. In
      addition, another member of this complex, hSNF5/INI1, is a known tumor suppressor
      gene (TSG) for malignant rhabdoid and childhood central nervous system tumors.
      Thus, BAF180 is a strong candidate TSG for lung cancer. The objective of this
      study was to determine whether BAF180 mRNA or protein expression was inactivated
      or abnormal in lung cancers to prompt detailed DNA promoter methylation or
      mutational analyses. In 30 non-small-cell and 26 small-cell lung cancer cell
      lines, most of which had 3p21 allele loss, BAF180 mRNA and protein expression
      were evaluated by RT-PCR using three sets of primers and Western blotting using
      two anti-BAF180 antibodies. In all cases, BAF180 was expressed and no abnormal
      size BAF180 protein was detected. Finally, we found no amino-acid sequence coding
      mutations in five non-small-cell and five small-cell lung cancer cell lines,
      while we did find a new splicing isoform of BAF180 (AY281068). We conclude that
      abnormalities of BAF180 are not frequently involved in the pathogenesis of lung
      cancer.

PMID- 15735768
TI  - [On the search for excellence: skills and requirements of modern cardio-thoracic
      and vascular surgery].
AB  - In this article the author evokes the figures of the past-presidents of the
      Portuguese Society for Cardio-Thoracic and Vascular Surgery, since its
      foundation, and enhances their qualities, regarded as examples for the new
      generations of cardio-thoracic and vascular surgeons in training. He approaches
      and describes the skills and personal requirements considered as essentials to be
      developed nowadays, by all those who dedicate their lives to those exciting and
      passionate surgical specialities.

PMID- 15735769
TI  - [Mitral valve repair in children for acquired valvular disease].
AB  - BACKGROUND: Valve surgery in children is aimed at restoring correct hemodynamics
      with few reoperations and limited resort to prostheses, which would imply early
      deterioration or definitive hypocoagulation. OBJECTIVES: Report a series of
      paediatric pts with acquired mitral valve disease, mostly due to rheumatic
      disease, in whom it was possible, for the great majority, to repair the damaged
      valve. DEMOGRAPHICS: Fifty children with predominant mitral valve disease, 47
      rheumatic (94%) and 3 after endocarditis were consequently operated by the same
      surgical team over the last five years. Ages were 12.5+/-3.1 yrs and weights
      33.2+/-8.4 Kg, 30 pts presented with predominant mitral regurgitation and 20 pts
      had significant stenosis. In 8 pts there also moderate to severe aortic
      regurgitation and in 2 pts severe tricuspid regurgitation was present. Patients
      were not operated during the acute phase of the disease. Five pts were
      reoperations and from those, all but one received mechanical prosthesis. RESULTS:
      In all operations the intention was to repair the mitral valve. In 46 pts complex
      mitral valvuloplasties were performed extended comissurotomies, shortening of
      chordae, chordal replacement with PTFE, and reconstruction of valve leaflefts by
      direct patching or pericardial extension of the retracted posterior leaflet
      (78.2% cases), plus reshaping of the annulus by using a fixed prosthetic CE ring
      (sizes 26 to 32) in every case. Ring sizes correlated poorly with body weights,
      but correlation was close and positive for the use of pericardial advancement of
      the posterior leaflet (p<0.01). There was no operative mortality, but one pt died
      early from sepsis and there was no late mortality. Maximum follow up extends now
      to 50 months (median 28 months) and functional evaluation, at latest follow up,
      as assessed by Doppler Echocardiography, showed residual mitral regurgitation,
      mild-moderate in 4 pts and LA-LV gradients mild in 5 and moderate in 2 pts. NYHA
      functional class, at present follow-up is class I for 43 pts (88%) and class II
      in the remaining 6 pts. Along the follow-up period 2 pts had to be reoperated for
      early repair failures and other three for late failures, presently freedom for
      reoperation is 91.8% at 5 years. CONCLUSIONS: Mitral valve repair in children
      with rheumatic lesions can be achieved for the great majority of cases by using
      different techniques. Pericardial extension of the retracted posterior leaflet
      allowed the use of a bigger size prosthetic ring. Intermediate functional results
      are good with fair functional classes and few reoperations but follow-up is short
      and does not allow us to draw conclusions about the long-term results of the
      repair in these rheumatic patients.

PMID- 15735770
TI  - [Coronary stenting--a success history].
AB  - Coronary stents are widely recognized as one of the most well succeeded
      achievements of modern intervention cardiology and were utilized in man, for the
      first time, since 1986. From that time until nowadays, they have been the subject
      of continuous improvements, as a consequence of a better understanding of their
      mechanisms of action and biologic behavior, which are described in detail in this
      article of revision.

PMID- 15735771
TI  - [Myocardial revascularization surgery, depressive symptoms and labeling effect].
AB  - INTRODUCTION: The individual awareness of one's own disease, the so called
      labeling effect, may result in a reduction of one's sense of perceived health. In
      patients submitted to coronary artery bypass surgery it has been reported that
      the diagnosis of depression is associated with a higher rate of hospitalization
      and it's an independent risk factor for cardiac events. The aim of this study was
      to evaluate the modification of depressive symptoms induced by the information of
      medical indication for myocardial revascularization surgery. METHODS: We studied
      the presence of depressive symptoms, socio-demographic variables, cardiovascular
      status and therapeutic procedures in two groups of consecutive patients admitted
      for acute coronary syndrome. In the labeled group the BDI-1 was performed after
      clinical stabilization and the BDI-2 after the information of myocardial
      revascularization surgery need. In the control group the BDI-1 was answered after
      clinical stabilization and the BDI-2 48-72 hours later. The Mann-Whitney test was
      used to compare the difference of depressive symptoms between the groups.
      RESULTS: Distribution by age, marital status and education level was similar
      between the two groups. The cardiovascular risk profile was alike. The difference
      between BDI-1 and BDI-2 was significantly higher in the labeled group (4.6-/+4.2
      vs 0.8-/+3.2; p=0.005). There were no significant differences between the final
      diagnosis (unstable angina in the labeled group 50% vs control group 45.5%; AMI
      without Q wave 30% vs 27.3%; AMI with Q wave 20% vs 27.3%) and in hospital
      clinical evolution. CONCLUSION: The individual awareness of the need to coronary
      bypass surgery was associated with a clinical and statistical significant
      increase of depressive symptoms. Hence, routine evaluation of depressive symptoms
      as a part of a preoperative protocol, may allow identification of the patients,
      who may benefit from therapeutic intervention.

PMID- 15735772
TI  - [Hypoplasias of the thoracic and abdominal aorta: presentation of two cases, with
      evaluation 11 and 20 years after surgical management].
AB  - Two cases of hypoplasia of the thoracic and abdominal aorta are reported,
      diagnosed in two individuals, a girl 13 years old and a boy aged 16 years. The
      malformation involved the upper abdominal aorta and the visceral arteries in the
      first case, and simply the descending thoracic aorta in the remainder. Arterial
      hypertension was the principal manifestation who lead to the diagnosis, which was
      confirmed through the conventional angiography. Both patients underwent surgical
      management, which consisted in the aortic revascularization associated to
      complete visceral revascularization in the first case, and in the single aortic
      revascularization in the second patient. Surgical therapy course was uneventful
      in both cases and blood pressure returned to normal values following the
      operation. Reviewed 11 and 20 years after the procedure, they were found in good
      condition, with normal blood pressure without any medication; angio CT studies
      disclosed the prosthetic grafts working in excellent condition. The main features
      of etiopathogeny, clinical presentation, diagnosis and surgical management are
      subjected to a discussion, based on an extensive review of the literature
      dedicated to this clinical entity.

PMID- 15735773
TI  - [The controversial use of dopamine in major vascular surgery].
AB  - Major vascular surgery patients are at great risk of renal failure. Several
      pharmacological and non pharmacological strategies have been developed to prevent
      renal failure in those patients. Renal doses of dopamine were used, based on its
      beneficial effects on renal function, in animals and healthy individuals.
      However, major vascular surgery patients are often critically ill, with diverse
      pathophysiological conditions and they cannot be easily compared to healthy
      individuals. There are, nowadays, enough scientific evidence demonstrating that
      renal doses of dopamine do not play a significant protective role of renal
      function in these critically ill patients.

PMID- 15735774
TI  - [Leg ulcers in Portugal: an underestimated health care problem].
AB  - To determine the prevalence and aetiology of leg ulceration in a population of
      patients registered with five health centres within Lisbon, a study was
      undertaken to identify patients receiving care from community and hospital.
      Identification of patients was through health professionals, with a simple
      questionnaire completed for all patients identified who were registered with the
      five health centres. In 263 patients were identified in a population of 186,000
      (total prevalence 1.41/1,000 population). The prevalence was similar between men
      and women (1.3 and 1.46/1,000, respectively). As expected this was highly age
      dependent, being most common in patients aged over 80 years (6.5 and 4.9/1,000,
      respectively). The ulceration was highly chronic in nature, with median
      ulceration of 18 months. Of the 240 with ulcer duration recorded, 158 (66%) had
      the present ulcer for longer than one year, and 40 (17%) for longer than five
      years. The cause of ulceration was unknown to the health professional treating
      the patient in 86 (33%) of the cases. Of those with a cause, most commonly this
      was venous (80%) with 10% mixed arterial/venous ulceration and 3% frank arterial
      disease. Most care was provided by community services, with 145 (55%) treated in
      health centres and 77 (29%) treated in the patient's home. The mean number of
      treatments per week was 3.0, with 21 (9%) of patients being seen on a daily
      basis. Most patients (80%) had seen a specialist doctor for their ulceration,
      most often a dermatologist (48%) and a vascular surgeon (33%). The prevalence of
      chronic leg ulceration is similar to other reported studies in western Europe,
      and indicates that approximately 14,000 patients suffer from leg ulceration at
      any one time in Portugal. This produces a high burden on both hospital and
      community services.

PMID- 15735775
TI  - [Lemierre's syndrome].
AB  - Lemierre's syndrome (LS) is an uncommon but potentially life-threatening
      complication of an anaerobic oropharyngeal infection, affecting young adults and
      adolescents. The disease is characterised by a septic thrombophlebitis of the
      internal jugular vein and "metastatic" infections, which can be followed by
      fulminant sepsis and rapid death. More recently, it has been reported a
      recrudescence of this condition, which could be attributable to alterations in
      antibiotic usage patterns. The authors report the case of a LS secondary to a
      bout of intense cough, a cause not yet described in the literature, highlighting
      the importance of a quick diagnosis and the institution of an appropriate
      therapy.

PMID- 15735776
TI  - [Multianeurismatic disease].

PMID- 15735777
TI  - Study of the evolution and degradation products of ciprofloxacin and oxolinic
      acid in river water samples by HPLC-UV/MS/MS-MS.
AB  - The results of a degradation study of the (fluoro)quinolone antibiotics
      ciprofloxacin and oxolinic acid in river water samples are presented in this
      paper. The decomposition of these compounds at ambient temperature was monitored
      during five months by HPLC-UV, and two consecutive degradation processes (photo-
      and bio/chemical-degradation) were observed in both cases although with different
      degradation rates. Ciprofloxacin was completely degraded after 3 months whereas
      80% of oxolinic acid remained unaltered after five months of storage. The
      analysis of the degradation compounds formed was carried out using MS and tandem
      MS-MS, allowing the identification of four new ciprofloxacin transformation
      products not previously described in the literature. Possible degradation
      pathways for this antibiotic in river water are proposed.

PMID- 15735778
TI  - The simultaneous modelling of metal ion and humic substance transport in column
      experiments.
AB  - Pulsed column experiments using Co, fulvic acid and porous sediment packing,
      along with up/down-flooding experiments using Eu, humic acid and intact sandstone
      blocks have been performed. The elution of metal and humic and their distribution
      along the sandstone columns have been measured. A mixed equilibrium and kinetic
      coupled chemical transport model has been used to simulate the results. In both
      cases, one exchangeable and one non-exchangeable component have been used to
      simulate the interaction of metal and humic substance. For the pulsed
      experiments, a simple equilibrium approach was used to model humic sorption,
      while a two component, kinetic model was required for the sandstone columns.

PMID- 15735779
TI  - Biomonitoring of tin and arsenic in different compartments of a limnic ecosystem
      with emphasis on Corbicula fluminea and Dikerogammarus villosus.
AB  - Asian clam Corbicula fluminea, the amphipod Dikerogammarus villosus and the
      macrophyte Nuphar lutea were tested for investigating spatial and temporal
      variability in the bioavailability of tin and arsenic in the River Lippe,
      Germany. Samples were collected from September 2002 to May 2003 at a tin polluted
      site (source pollution) and a reference site. Additional screening sampling was
      carried out twice in April 2003 to test the extent of As and Sn concentration in
      periphyton (aufwuchs) samples. Accumulated Sn and As concentrations were measured
      with ICP-MS after sample processing (dissection, cryo-milling) and digestion.
      Quality control was performed by parallel analysis of three certified reference
      materials. Measurable As and Sn contents in plant tissues were only detectable in
      roots (below 30 microg kg(-1) and 20 microg kg(-1) for As and Sn, respectively).
      Homogenates from C. fluminea and D. villosus tissues showed site-dependent trace
      metal contents. Elevated bioavailability of Sn is present downstream of the
      sewage discharge of the world's biggest producer of tributyltin (TBT) at Luenen
      (northern Ruhr region). In comparison to C. fluminea, D. villosus shows higher
      concentrations of tin in samples from both sites. Arsenic concentrations in C.
      fluminea remain constant with increasing shell size, whereas tin shows a size
      dependent accumulation. The results indicate that Corbicula fluminea and
      Dikerogammarus villosus are suitable passive biomonitoring organisms for Sn, but
      As levels might be actively regulated. The concentration of tin in the periphyton
      (aufwuchs) samples was found to be much higher in samples from a contaminated
      site (428 +/- 63 vs. 1949 +/- 226 microg kg(-1)).

PMID- 15735780
TI  - The use of the oyster Saccostrea glomerata as a biomonitor of trace metal
      contamination: intra-sample, local scale and temporal variability and its
      implications for biomonitoring.
AB  - Cu, Cd, Zn, Pb and Se concentrations were measured in the bivalve mollusc
      Saccostrea glomerata(Iredale and Roughly) from two uncontaminated locations,
      Clyde River Estuary, Batemans Bay and Moona Moona Creek, Jervis Bay, to determine
      natural variability of metals associated with mass, gender, age, tissue type and
      site within location. Trace metals were also measured in the Clyde River Estuary
      over an 11 year period and in five other NSW estuaries (Hastings River, Hunter
      River, Georges River, Tillgerry Creek and Lake Pambula) over a 13-month period to
      determine temporal variability and if diploid and triploid oysters accumulate
      trace metals differently. There were few significant relationships between trace
      metal concentrations and mass and no significant differences in trace metal
      concentrations between female and male oysters. Younger oysters (1.3 years) had
      significantly higher copper concentrations and higher trace metal variability
      than mature oysters (3 years). Different tissues have different trace metal
      concentrations with muscle tissues having lower concentrations. Considerable
      inherent variability occurs in oyster cohorts. Analysing specific tissues did not
      reduce variability of trace metal concentrations. Comparison of trace metal
      concentrations at two sites within the Clyde Estuary showed a significant
      difference in zinc concentrations. Cu, Cd, Zn and Se concentrations were
      generally higher and less variable in triploids than diploids. Pb had a variable
      pattern of accumulation with no consistent elevation in diploids or triploids.
      Inter annual variability of trace metal concentrations was considerable and trace
      metal concentrations also fluctuated throughout an annual cycle with no clear
      seasonal trends. Measurement of trace metals at known contaminated locations
      showed that Saccostrea glomerata accumulates metals in response to contamination.
      Saccostrea glomerata meet most of the requirements to be a biomonitor of trace
      metal contamination as they are abundant, sessile/sedentary, easy to identify,
      provide sufficient tissue for analysis, and accumulate trace metals in response
      to contamination. However, as trace metal concentrations can vary with mass, age,
      estuary position, ploidy type and temporally, care must be taken to collect
      individual organisms of similar mass, age and ploidy type to minimise
      variability, and from similar consistent positions and times to allow for
      seasonal changes in environmental conditions. Trace metal concentration
      variability is higher in young animals, thus to reduce variability, older mature
      animals could be selected. However, with immature oysters there are no
      complications because of the effects of spawning i.e. sudden loss of trace metals
      or body mass.

PMID- 15735782
TI  - Grid search: an innovative method for the estimation of the rates of lead
      exchange between body compartments.
AB  - This paper describes a new metabolic model for lead in humans and a numerical
      method to solve the differential equations governing the transfer of lead between
      body compartments. The model includes 3 compartments-cortical bone, trabecular
      bone and blood-and accounts for absorption from external sources and release
      through excreta. Estimation of the lead kinetics parameters was performed using
      the grid search method. Grid search is a simple procedure that allows the fit of
      an arbitrary function to data. When applied to data from occupationally exposed
      populations, the method demonstrated the exposure dependence of the rate of lead
      uptake and release by the compartments in the model. The results confirm and
      refine previous observations of the significant decrease of the transfer rate of
      lead from cortical bone to blood with increasing exposure, as expressed by half
      lives of (in years): 6.5 +/- 0.7, 13.6 +/- 1.0 and 47.5 +/- 2.3, in subgroups of
      low, intermediate and high long-term lead exposure. A similar trend was observed
      for the transfer rate from trabecular bone, which could be statistically
      supported for the first time. Reduction by a factor of 7 to 10 in the default
      values assigned to the fractional removal of lead from cortical bone to plasma in
      existing metabolic models was also predicted. These results can be used in the
      review of current metabolic models for lead, which are still based on the
      assumption of a constant rate of lead removal from bone, independently of the
      level of exposure.

PMID- 15735781
TI  - One-year monitoring survey of organic compounds (PAHs, PCBs, TBT), heavy metals
      and biomarkers in blue mussels from the Arcachon Bay, France.
AB  - Marine mussels Mytilus sp. were transplanted on a monthly basis in cages over one
      year to oyster farms and harbours in the Arcachon Bay (France) in order to assess
      the water quality of the bay. Contaminant levels (organotin compounds, trace
      metals, PCBs and PAHs) were measured in tissues of transplanted mussels and
      mussels from a reference station, along with physiological parameters of the
      mussels (condition indexes, lipid content and dry weight). Four biomarkers (AChE:
      acetylcholinesterase activity, GST: gluthathione S-transferase activity, CAT:
      catalase activity and TBARS: thiobarbituric acid-reactive substance content) were
      also monitored. The remote stations monitored (oyster parks) exhibited no
      accumulation pattern of pollutants. Their respective concentrations therefore
      constitute a background level of the contamination in the bay ([TBT]= 30 ng Sn g(
      1) dw, [SigmaHAPs]= 100 ng g(-1) dw, [SigmaPCBs]= 35 ng g(-1) dw). The elevated
      chemical contamination of the largest harbour of the bay, the Arcachon harbour,
      can be interpreted in terms of persistence of organotin compounds ([SigmaOTs]=
      1500-2000 ng Sn g(-1) dw) and PAHs ([SigmaHAPs]= 4500-5000 ng g(-1) dw) in
      sediments and, to a lesser extent, of direct inputs of copper ([Cu]= 20 microg g(
      1) dw in harbours versus 7 in oyster parks) and petrogenic PAHs
      ([methylphenanthrenes]= 1600 ng g(-1) dw in the dockyard versus 170 at the gas
      stations), related to the use of copper-based antifouling paints and to dockyard
      activity, respectively. However, the Arcachon Bay presents a low contamination
      level by PCBs and metals, including harbour stations. Furthermore, higher levels
      of other PAHs (particularly alkyl PAHs such as methylphenanthrenes/1600 ng g(-1)
      dw) not included in the 16 PAHs from the EPA priority list (usually studied in
      biomonitoring programmes/1500 ng g(-1) dw) in the Arcachon harbour underline the
      need to integrate these compounds in biomonitoring of highly PAH-polluted areas
      such as harbours in order to avoid misinterpretation of the biological responses
      observed. Biomarker responses were not able to discriminate the different
      chemical contamination levels recorded in the Arcachon Bay and rather reflected
      changes in environmental factors. Furthermore, the strong intraspecies
      variability of biological responses could be due to genetic differences of
      mussels from the Arcachon Bay. It is the first time that such an integrated
      monitoring is performed in the Arcachon Bay, also taking into account seasonal
      variations of chemical contents and biomarkers levels in mussel tissues.

PMID- 15735783
TI  - 24 h diffusive sampling of toxic VOCs in air onto Carbopack X solid adsorbent
      followed by thermal desorption/GC/MS analysis-laboratory studies.
AB  - Diffusive sampling of a mixture of 42 volatile organic compounds (VOCs) in
      humidified, purified air onto the solid adsorbent Carbopack X was evaluated under
      controlled laboratory conditions. The evaluation included variations in sample
      air temperature, relative humidity and ozone concentration. Linearity of samples
      with loading was examined both for a constant concentration with time varied up
      to 24 h and for different concentrations over 24 h. Reverse diffusion and its
      increase with accumulation of sample were determined for all compounds. Tubes
      were examined for blank levels, change of blanks with storage time, and
      variability of blanks. Method detection limits were determined based on seven
      replicate samples. Based on this evaluation, 27 VOCs were selected for
      quantitative monitoring in the concentration range from approximately 0.1 to 4
      ppbv. Comparison results of active and diffusive samples taken over 24 h and
      under the same simulated ambient conditions at a constant 2 ppbv were interpreted
      to estimate the effective diffusive sampling rates (ml min(-1)) and their
      uncertainties and to calculate the corresponding diffusive uptake rates (ng ppmv(
      1) min(-1)).

PMID- 15735784
TI  - Real-time quantitative PCR with gene probe, fluorochrome and flow cytometry for
      microorganism analysis.
AB  - Microorganism concentrations and viability can be better understood and clarified
      by using both culture and non-culture methods. Here, using pure suspensions of E.
      coli, three non-culture methods, namely, flow cytometry (FCM), epifluorescence
      microscopy (EFM), and real-time quantitative polymerase chain reaction (real-time
      qPCR), were compared with a traditional culture-based method. Using fluorocome
      labeling methods with FCM and EFM applications, acridine orange (AO) and
      propidium iodide (PI) dyes were used to determine the total cell concentration
      and microorganism viability, respectively. The results indicated that total cell
      concentrations determined using FCM were statistically higher (2.62-4.94 times)
      than those determined using EFM. The difference might be due to cell losses
      induced by extensive preparations needed for EFM. In addition, EFM and FCM were
      highly associated for both the total cell concentration and viability. FCM
      measured viability was the highest, whereas the culture-measured viability was
      the lowest. Furthermore, DNA concentrations measured by real-time qPCR with gene
      probe were highly associated with the total number concentrations measured by
      either the EFM or FCM. In summary, the three non-culture methods compared here
      could provide rapid and accurate information about microorganism concentrations
      and viabilities.

PMID- 15735785
TI  - A spoonful of sugar helps the medicine go down... but platelet eNOS activity go
      up!

PMID- 15735786
TI  - Genetic variation in the fibrinogen gene cluster.

PMID- 15735787
TI  - Effects of human cytomegalovirus infection on the coagulation system.
AB  - Pathophysiological mechanisms of acute vascular thrombosis are not fully
      understood. It has been suggested that different infectious pathogens are
      responsible agents of thrombotic disorders. The infection hypothesis is supported
      by an increasing number of reports on the interaction between acute infection and
      coagulation. Cytomegalovirus (CMV) is supposed to play an important role in
      apparently unprovoked thrombosis. We reviewed all human in vitro and in vivo
      studies on the influence of human CMV infection on the coagulation system, as
      well as all case reports of acute thrombosis during acute human CMV infection. In
      the published literature there is mounting evidence that human CMV may play a
      role in thrombotic disorders. Definitive conclusions, however, cannot be drawn,
      although the in vitro studies are convincing and offer insight in the
      pathogenesis.

PMID- 15735788
TI  - Protein Z and protein Z-dependent protease inhibitor. Determinants of levels and
      risk of venous thrombosis.
AB  - To assess the potential roles of protein Z (PZ) and protein Z-dependent protease
      inhibitor (ZPI) in venous thrombosis, their plasma levels were measured in 426
      individuals with venous thrombosis and 471 control individuals participating in
      the Leiden Thrombophilia Study. A relationship between the level of PZ or ZPI and
      venous thrombosis was not detected in the overall case-control study. PZ and ZPI
      circulate as a complex and their plasma levels are interdependent. Both PZ and
      ZPI are increased with oral contraceptive use and reduced with oral anticoagulant
      therapy.

PMID- 15735789
TI  - Molecular mechanism of dysfunctional factor VII associated with the homozygous
      missense mutation 331Gly to Ser.
AB  - We have identified a Japanese homozygous FVII deficiency associated with the
      mutation G331S (c184 [in chymotrypsin numbering]), and have determined the
      mechanisms responsible for the dysfunctional FVII variant by expressing the
      mutant recombinant FVII protein. In addition, the recombinant proteins FVIIG331D,
      G331W and G331F were expressed. The purified recombinant FVII proteins ran as a
      single chain form on SDS-PAGE having a molecular mass of approximately 50 Kda.
      The recombinant FVIIG331S expressed the level of the recombinant wild type FVII
      at 2.0%, and this mutant form was also similar to FVII in the patient's plasma.
      However, the amidolytic activity of FVIIa using peptidyl substrate S-2288
      differed little between the wild type and the four mutant FVII molecules. We
      suggest that the functional defect found in these mutants is not directly
      associated with peptidyl substrate recognition or catalysis. The Km values of FX
      and FIX for the mutant proteins were approximately 7.6- to 15-fold and 13- to 19
      fold higher than those for the wild-type protein, respectively. Molecular
      modelling indicated that the side chain of the S331 mutant is oriented close to
      the side chain of D338 (c189) at the bottom of the specificity pocket of FVIIa.
      We show that the replacement of G331 with a serine likely results in a steric
      hindrance of macromolecular substrate binding, leading to a loss of FVIIa
      enzymatic activity.

PMID- 15735790
TI  - Gene duplication of coagulation factor V and origin of venom prothrombin
      activator in Pseudonaja textilis snake.
AB  - The origin and evolution of venom toxins is a mystery that has evoked much
      interest. We have recently shown that pseutarin C, a prothrombin activator from
      Pseudonaja textilis venom, is structurally and functionally similar to mammalian
      coagulation factor Xa-factor Va complex. Its catalytic subunit is homologous to
      factor Xa while the nonenzymatic subunit is homologous to factor Va. P. textilis
      therefore has two parallel prothrombin activator systems: one expressed in its
      venom gland as a toxin and the other expressed in its liver and released into its
      plasma as a haemostatic factor. Here we report the complete amino acid sequence
      of factor V (FV) from its liver determined by cDNA cloning and sequencing. The
      liver FV shows 96% identity to pseutarin C nonenzymatic subunit. Most of the
      functional sites involved in its interaction with factor Xa and prothrombin are
      conserved. However, many potential sites of post-translational modifications and
      one critical cleavage site for activated protein C are different. The absence of
      the latter cleavage site makes pseutarin C nonenzymatic subunit resistant to
      inactivation and enhances its potential as an excellent toxin. By PCR and real
      time quantitative analysis, we show that pseutarin C nonenzymatic subunit gene is
      expressed specifically in the venom gland at approximately 280 fold higher than
      that of FV gene in liver. These two are thus encoded by two separate genes that
      express in a highly tissue-specific manner. Our results imply that the gene
      encoding pseutarin C nonenzymatic subunit was derived by the duplication of
      plasma FV gene and they have evolved to perform distinct functions.

PMID- 15735791
TI  - Improvement of the specificity of dipetarudin by site directed mutagenesis.
AB  - Protease specificity is crucial to the design of thrombin inhibitors as
      inhibition of other physiologically relevant serine-proteases can compromise
      their clinical use. Dipetarudin, a potent thrombin inhibitor, also inhibits
      trypsin and plasmin. Due to the specificity of an inhibitor being influenced by
      the amino acid residue at the P1 position, we replaced the Arg10 at P1 position
      of dipetarudin by a histidine, which is the P1 residue of rhodniin, a very
      specific thrombin inhibitor. The amino acid replacement was carried out by site
      directed mutagenesis. The mutant, dipetarudinR10H, showed a loss of plasmin and
      trypsin inhibitory activities present in its wild-type counterpart and a 3-fold
      higher dissociation constant for thrombin than dipetarudin. However, compared to
      dipetarudin and r-hirudin, dipetarudinR10H showed similar activity in coagulation
      screening assays such as activated partial thromboplastin time (aPTT),
      prothrombin time (PT), ecarin clotting time (ECT) and ecarin chromogenic assay
      (ECA).

PMID- 15735792
TI  - Antithrombotic potential of new direct thrombin inhibitors built on the
      azaphenylalanine scaffold in two rat venous thrombosis models.
AB  - The antithrombotic potential of new direct thrombin inhibitors built on the
      azaphenylalanine scaffold (LK-732, LK-639 and LK-731) and their amidoxime
      prodrugs (LK-658, LK-633 and LK-730) was studied in comparison to argatroban and
      nadroparin in two rat models of venous thrombosis, induced either by complete
      stasis combined with hypercoagulability (model 1) or by partial stasis combined
      with vessel injury (model 2). In initial experiments LK-732 was established as
      the most promising antithrombotic of the LK inhibitors and as such was further
      tested. In model 1, intravenous bolus administration of LK-732 produced a dose
      dependent inhibition of thrombus formation with an ID50 value of 1.3 mg/kg. This
      ID50 value was approximately four times higher than the ID50 value of argatroban
      (0.3 mg/kg; p=0.011). However, in model 2, LK-732 and argatroban decreased
      thrombus weight by 50% at similar ID50 values (3.8 mg/kg vs 3.0 mg/kg,
      respectively; p=0.726). The ex vivo anticoagulant effect of LK-732 was
      substantially weaker compared to argatroban at doses that produced comparable
      antithrombotic effects. After subcutaneous administration, in vivo thrombus
      weight reduction of LK inhibitors (10 mg/kg) ranged between 22 to 48%. However,
      their oral antithrombotic effect at a dose of 30 mg/kg was rather low. LK
      amidoxime prodrugs failed to produce a substantial antithrombotic effect after
      subcutaneous (10 mg/kg) as well as after oral administration (30 mg/kg). In
      conclusion, thrombin inhibitors built on the azaphenylalanine scaffold represent
      a new group of intravenously effective antithrombotics. However, optimisation of
      the oral antithrombotic effect of amidoxime prodrug LK-658 of the lead inhibitor
      LK-732 is required for justifying further development of these inhibitors.

PMID- 15735793
TI  - Complement activation: the missing link between ADAMTS-13 deficiency and
      microvascular thrombosis of thrombotic microangiopathies.
AB  - Endothelial injury is the central factor in the events leading to thrombotic
      microangiopathy (TMA); however, the mechanisms involved are not fully understood.
      Here we investigate the role of neutrophils (PMNs) and of complement activation
      in inducing microvascular damage and loss of thromboresistance in TMA associated
      with ADAMTS-13 deficiency. PMNs isolated during the acute phase of the disease
      released excessive amounts of reactive-oxygen species (ROS), N-derived oxidants
      and proteinases and induced damage and thromboresistance loss in human
      microvascular endothelial cell line (HMEC-1) ex vivo. Endothelial cytotoxicity
      and thromboresistance loss was also induced by TMA serum. Complement-derived
      products were responsible for the above effects: in fact, TMA serum caused C3 and
      Membrane Attack Complex (MAC) deposition on HMEC-1 and its cytotoxic effect was
      abolished by complement inhibition. TMA serum caused surface expression of P
      selectin on HMEC-1 which may promote PMN adhesion and resulted in increased PMN
      cytotoxicity, indicating that complement may have a role in PMN activation. In
      addition, TMA serum stimulated control PMNs to release ROS and proteinases, and
      to cause endothelial cell cytotoxicity. All of the above effects were abrogated
      by complement inactivation. These data document for the first time that
      complement-initiated PMN activation and endothelial injury may have a crucial
      role in microvascular thrombosis of TMA associated with ADAMTS-13 deficiency.

PMID- 15735794
TI  - The factor VIII D1241E polymorphism is associated with decreased factor VIII
      activity and not with activated protein C resistance levels.
AB  - Elevated factor VIII (FVIII) levels are a recognized risk factor for venous
      thrombosis. Recently, family studies suggested that the G allele of the 3951C/G
      (D1241E) FVIII polymorphism is associated to lower FVIII activity. We
      investigated in case-control studies both biological effects (FVIII levels and
      activated protein C sensitivity ratio) and clinical associations (venous
      thromboembolism) of the D1241E change. Among 145 healthy and 150 thrombotic
      women, not carriers of known thrombophilic defects, the 1241E allele was
      associated with 11% reduced (t-test, P<0.05) FVIII levels. The effect on
      activated protein C sensitivity ratio was not statistically significant.
      Carriership of the 1241E allele, potentially conferring protection from
      thrombosis, was found in 22.8% of controls and in 15.3% of cases. In an
      additional cohort of factor V Leiden carriers (n=283), carriership of the 1241E
      allele was 25.2% among 143 asymptomatic subjects and 17.1% among 140 thrombotic
      patients. Our data do not indicate a specific interaction with factor V Leiden.
      These genotype distributions suggest a mild protective effect from venous
      thrombosis conferred by 1241E FVIII, masked by other genetic and/or environmental
      components, and detectable only in very large population studies. Our findings
      point toward the presence of genetic determinant of coagulation factor levels
      with a biologically significant role, but with a poor predictive value to
      estimate thrombotic risk beyond established risk factors.

PMID- 15735795
TI  - Full-length sucrose-formulated recombinant factor VIII for treatment of
      previously untreated or minimally treated young children with severe haemophilia
      A: results of an international clinical investigation.
AB  - The safety and efficacy of a full-length sucrose-formulated recombinant factor
      VIII product (rFVIII-FS; Kogenate FS; Kogenate Bayer) was evaluated in previously
      untreated (PUPs) and minimally treated (MTP) patients with severe haemophilia A
      (FVIII <2%). Patients (37 PUPs; 24 MTPs) aged 0.1-25.7 months were treated with
      rFVIII-FS for a cumulative of 9,141 exposure days (EDs), median 114 EDs (range 4
      478), on prophylactic or on-demand therapy. Eighty-nine percent of all treated
      bleeding episodes were successfully treated with 1 (74%) or 2 (15%) infusions.
      Clinical response to first infusion for each bleeding episode was rated as
      'excellent' in 58%, or 'good' in 33%, of all cases. Recombinant FVIII-FS was used
      in 27 surgical procedures, mainly catheter implantations, which were all
      conducted without bleeding complications. FVIII recovery mean values
      (approximately 2%/kg/IU) were as expected for any licensed FVIII concentrate.
      FVIII neutralizing antibody formation was 15% (9/60). Aside from inhibitor
      formation, three adverse events were rated as 'at least possibly drug-related'
      for a total drug-related adverse event rate of 0.14%. No viral seroconversions
      were observed. Overall, excellent safety and efficacy were demonstrated with
      rFVIII-FS for therapy of young children with severe haemophilia A.

PMID- 15735796
TI  - The ABO blood group genotype and factor VIII levels as independent risk factors
      for venous thromboembolism.
AB  - Factor VIII (FVIII), von Willebrand factor (vWF) and the ABO blood groups have
      been associated with thrombosis. The ABO locus has functional effects on vWF and
      FVIII levels and is genetically correlated with FVIII, vWF and thrombosis. We
      carried out a case-control study to assess the role of FVIII, vWF and ABO types
      on thrombotic risk. We analyzed 250 patients with venous thrombosis and 250
      unrelated controls. FVIII, vWF and other factors related to thrombophilia were
      measured, ABO groups were analyzed by genotyping. FVIII and vWF were higher in
      non-O individuals. Group O was more frequent in the controls (44.3% v 23.3%;
      difference 21.1%; 95% CI: 13.0-29.3%) and Group A in patients (59.2% v. 41.5%;
      difference 17.7%, 95% CI: 9.1-26.4%). Individuals carrying the A1 allele had a
      higher risk of thrombosis (OR 2.6; 95% CI, 1.8-3.8). The risk attributed to vWF
      disappeared after adjusting for the ABO group. Patients with FVIII above the 90th
      percentile had a high thrombotic risk (adjusted OR 3.7; 95% CI, 2.1-6.5), and a
      high risk of recurrence (OR 2.3; 95% CI: 1.3-4.1). In conclusion, high FVIII
      levels and non-O blood groups, likely those with the A1 allele, are independent
      risk factors for venous thromboembolism and should be considered in evaluating of
      thrombophilia.

PMID- 15735797
TI  - Evaluation of thrombin generating capacity in plasma from patients with
      haemophilia A and B.
AB  - In haemophilia patients, a relationship is usually observed between the clinical
      expression of the disease and plasmatic factor VIII/factor IX (FVIII/FIX)
      activity. However, it is known from clinical experience, that some haemophilia
      patients, despite similar FVIII/FIX plasma levels, could exhibit different
      bleeding phenotype. After determining preanalytical test conditions, we evaluated
      the thrombin generation capacity from haemophilia plasma samples in various
      conditions and the potential usefulness of thrombin generation test (TGT) in
      haemophilia patients. In a series of 46 haemophilia patients (34 haemophilia A
      and 12 haemophilia B patients), we found a significant correlation between
      plasmatic FVIII/FIX levels and endogenous thrombin potential (ETP), peak and time
      to peak obtained by thrombin generation measurement. In addition, a correlation
      was found between severe clinical bleeding phenotype and ETP. Our results suggest
      that TGT could be a promising tool to evaluate haemostasis capacity in patients
      with haemophilia. Our ex vivo results, obtained 24 hours after FVIII concentrate
      administration, showed that in patients presenting similar plasmatic FVIIII
      levels, thrombin generation capacity may be significantly different. These
      results suggest that in patients with haemophilia, TGT could be useful for
      individually tailoring prophylactic regimens as well as for adapting clotting
      factors infusions in surgical situations, in addition to FVIII/FIX plasma
      clotting activities.

PMID- 15735798
TI  - Clinical phenotypes and factor VII genotype in congenital factor VII deficiency.
AB  - To investigate the relationship between clinical phenotype, clotting activity
      (FVIIc) and FVII genotype, a multi-center study of factor VII (FVII) congenital
      deficiency with centralized genotyping and specific functional assays was carried
      out. FVII mutations characterized in patients (n=313) were extremely
      heterogeneous (103 different, 22 novel). Clinical phenotypes ranged from
      asymptomatic condition, including 15 homozygotes and 14 double heterozygotes, to
      patients with a severe disease characterized by life-threatening and disabling
      symptoms (CNS, GI bleeding and hemarthrosis) strongly associated with an early
      age of presentation. Based on type and number of symptoms we classified 90
      'severe' (median FVIIc 1.4%, IQR [Interquartile Range] 0.9-3.8), 83 'moderate'
      (FVIIc 3%, IQR 1-21.7), and 140 'mild' bleeders (FVIIc 14%, IQR 3-31). The
      significantly different FVIIc levels, and the decreasing prevalence of
      homozygotes or double heterozygotes among severe (98%), moderate (84%) and mild
      (56%) bleeders, further support our classification. The excess of females among
      moderate bleeders (female/male ratio = 2.6) is attributable to menorrhagia. There
      was no evidence for modulation of clinical features by frequent functional
      polymorphisms. Homozygotes for the same mutation (Ala294Val; 11125delC) with
      similar FVIIc and FXa generation levels, showed striking differences in clinical
      phenotypes. Our study depicts the ample clinical picture of this rare disorder,
      proposes a severity classification and provides arguments for the early
      management of the disease in the severe cases. Genotype-phenotype relationships
      indicate the presence of major environmental and/or extragenic components
      modulating expressivity of FVII deficiency.

PMID- 15735799
TI  - Basal high-sensitivity-C-reactive protein levels in patients with spontaneous
      venous thromboembolism.
AB  - The role of C-reactive protein (CRP) in venous thromboembolism (VTE) is still
      under discussion because of controversial results in the literature. Conflicting
      data may have partly been due to bias by exogenous factors altering CRP levels.
      We investigated CRP concentrations in patients with spontaneous VTE applying a
      study design that allowed the measurement of basal high sensitivity (hs)-CRP
      levels. Patients with a history of deep vein thrombosis (DVT, n=117) and
      pulmonary embolism (PE, n=97) were compared to healthy individuals (n=104). Hs
      CRP levels (mg/dl) were significantly higher in patients (n=214,
      median/interquartile range: 0.171/0.082-0.366) than in controls (0.099/0.053
      0.245, p=0.001). The unadjusted odds ratio (OR) for VTE per 1 mg/dl increase of
      CRP was 2.8 [95% confidence interval (CI): 1.1-6.8, p=0.03]. This association
      remained significant after adjustment for factor V Leiden, prothrombin G20210A
      and factor VIII activity above 230% (OR = 2.9, 95% CI [1.1-7.5]), but became
      remarkably attenuated and lost its statistical significance after adjustment for
      BMI alone (OR = 1.7 [0.7-4.0]). CRP was also not independently associated with
      VTE in subgroups of patients (those with DVT without symptomatic PE, those with
      PE and patients without established risk factor) in multiple regression analysis.
      In summary, we observed significantly higher basal hs-CRP levels in patients with
      spontaneous VTE compared to healthy controls. This association was independent of
      hereditary and laboratory risk factors for VTE, but lost its significance after
      adjustment for BMI. Increased basal CRP levels do not appear to represent an
      independent risk factor for VTE.

PMID- 15735800
TI  - Risk factors associated with symptomatic pulmonary embolism in a large cohort of
      deep vein thrombosis patients.
AB  - In patients with deep vein thrombosis (DVT), the factors which predispose to
      concomitant symptomatic pulmonary embolism (PE) have remained uncertain. From a
      prospective cohort of 5,451 consecutive patients with ultrasound-confirmed DVT,
      we analyzed 4,211 patients with a known status for presence (n=639) or absence
      (n=3572) of symptomatic PE. Age and gender were similar in DVT plus PE (63.7+/
      15.6 years; 49% men) and DVT patients (63.4+/-17.3 years; 46% men). Body mass
      index (BMI) was higher in patients with DVT plus PE (median 29.0, range 15.4-67.0
      kg/m2) than in patients with DVT (median 26.8, range 9.7-64.4 kg/m2; p<0.001).
      Chronic lung disease (17% vs. 12%; p<0.001), a personal history of PE (11% vs.
      6%; p<0.001), and a family history of DVT or PE (8% vs. 4%; p<0.001) were more
      frequent in DVT plus PE patients. Twenty-seven percent of DVT plus PE patients
      received prophylaxis prior to the thromboembolic event compared with 32% of DVT
      patients (p=0.002). Proximal DVT (OR 1.84, 95% CI 1.39-2.43), prior PE (OR 1.68,
      95% CI 1.20-2.35), obesity (BMI >30 kg/m2) (OR 1.65, 95% CI 1.33-2.04), chronic
      lung disease (OR 1.51, 95% CI 1.13-2.01), as well as omission of prophylaxis (OR
      1.30, 95% CI 1.04-1.64) emerged as independent predictors of concomitant
      symptomatic PE.

PMID- 15735801
TI  - Post-thrombotic syndrome, functional disability and quality of life after upper
      extremity deep venous thrombosis in adults.
AB  - The post-thrombotic syndrome (PTS) after upper extremity deep venous thrombosis
      (UEDVT) has not been well characterized. The objective of our study was to
      describe and quantify residual symptoms, functional disability and quality of
      life associated with PTS after UEDVT in adults. Twenty-four patients with
      objectively diagnosed UEDVT (bilateral in 1 patient) at least 6 months previously
      were recruited from two Canadian thrombosis clinics. Data were collected on
      demographic characteristics, DVT risk factors and affected venous segments. The
      Villalta PTS scale, modified for the upper extremity, was used to diagnose PTS.
      Patients completed questionnaires on degree of functional disability (DASH
      questionnaire), and generic (SF-36) and disease-specific (VEINES-QOL) quality of
      life. Results were compared in patients with and without PTS. Patients were
      assessed a median of 13 months after the diagnosis of UEDVT. Daily ipsilateral
      arm or hand swelling was reported by 52% of patients and daily ipsilateral arm
      pain by 20% of study patients, compared with 0% and 0%, respectively, in the
      contralateral arm. PTS was present in 11/25 (44%) limbs (11/24 patients). One
      patient had severe PTS. Patients with PTS, compared with those without PTS, had
      significantly more functional disability (mean DASH score 20.9 vs. 3.7, p=0.009)
      and poorer quality of life (mean VEINES-QOL score 45.6 vs. 53.6; p=0.001; mean SF
      36 Physical Component Score (PCS) 40.8 vs. 50.2; p=0.12). PTS scores were higher
      and quality of life was poorer when PTS involved the dominant arm. In conclusion,
      PTS occurs frequently after UEDVT and is associated with significant functional
      disability and reduced quality of life. Patients with dominant arm PTS appear to
      fare worse than those with non-dominant arm PTS. Larger, prospective studies to
      identify prognostic factors that lead to PTS after UEDVT are warranted.

PMID- 15735802
TI  - Performance of magnetic resonance angiography in suspected acute pulmonary
      embolism.
AB  - Pulmonary embolism (PE) is a common and potentially fatal disorder. Non-specific
      findings make the clinical diagnosis of PE difficult. To assess the diagnostic
      value and inter-observer agreement of magnetic resonance angiography (MRA) in a
      cohort of patients with suspected PE, we conducted a prospective clinical study.
      MRA was compared for sensitivity and specificity to a diagnostic strategy
      including clinical probability, D-dimer testing, spiral CT, ultrasound leg
      compression and pulmonary angiography. A total of 89 patients with clinically
      suspected PE were included: the clinical probability of PE was intermediate or
      high in 78, and low in the remaining 11. All patients underwent monoor multi
      slice spiral CT and MRA with gadolinium injection (both within 24 hours of entry
      to the study). Anticoagulation was withheld in patients concerned about the
      strategy. All subjects were followed up for 3 months. MRA was read independently
      by two experienced teams of radiologists: one local and one from another
      university centre. Spiral CT was positive in 62 of 63 cases of confirmed PE. No
      patient with negative CT findings was positive ultrasonographically. Only one
      patient with a negative CT (and negative ultrasound) had a recurrent
      thromboembolic event. The first team diagnosed PE with MRA in 47 cases, with a
      sensitivity of 71% and a specificity of 92%; the second team obtained the
      diagnosis in 23 cases, with a sensitivity of 31% and a specificity of 85%. Inter
      observer agreement between MRA reading was low: Kappa = 0.16 (-0.01 to 0.33); p =
      0.07. In conclusion, compared with a non-invasive strategy based on spiral CT,
      the diagnostic value of MRA is limited by poor inter-observer agreement.

PMID- 15735803
TI  - Medical conditions increasing the risk of chronic thromboembolic pulmonary
      hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by
      organized thromboemboli that obstruct the pulmonary vascular bed. Although CTEPH
      is a serious complication of acute symptomatic pulmonary embolism in 4% of cases,
      signs, symptoms and classical risk factors for venous thromboembolism are
      lacking. The aim of the present study was to identify medical conditions
      conferring an increased risk of CTEPH. We performed a case-control-study
      comparing 109 consecutive CTEPH patients to 187 patients with acute pulmonary
      embolism that was confirmed by a high probability lung scan. Splenectomy (odds
      ratio=13, 95% CI 2.7-127), ventriculo-atrial (VA-) shunt for the treatment of
      hydrocephalus (odds ratio=13, 95% CI 2.5-129) and chronic inflammatory disorders,
      such as osteomyelitis and inflammatory bowel disease (IBD, odds ratio=67, 95% CI
      7.9-8832) were associated with an increased risk of CTEPH.

PMID- 15735804
TI  - High glucose rapidly activates the nitric oxide/cyclic nucleotide pathway in
      human platelets via an osmotic mechanism.
AB  - The aim was to evaluate whether high glucose influences the nitric oxide
      (NO)/cyclic nucleotide pathway in human platelets via osmotic stress and to
      clarify the role of protein kinase C (PKC) in this phenomenon. The study was
      carried out on 33 healthy lean male volunteers, aged 28.3+/-1.3 years. NO
      synthesis was detected as L-citrulline production after L-arginine incubation in
      platelets incubated for 6 min with 22.0 mM D-glucose and iso-osmolar
      concentrations of mannitol, L-glucose and fructose. To evaluate the influence of
      PKC, experiments with D-glucose and mannitol were repeated in the presence of the
      PKC-beta selective inhibitor LY379196, and NO synthesis was detected after a 6
      min incubation with phorbol 12-myristate 13-acetate (PMA), a non-selective PKC
      activator. Platelet content of guanosine-3',5'-cyclic monophosphate (cGMP) and
      adenosine-3',5'-cyclic monophosphate (cAMP) was measured by radioimmunoassay in
      platelets incubated with iso-osmolar concentrations of D-glucose, mannitol, L
      glucose and fructose. NO-dependence of cyclic nucleotide enhancements was
      evaluated by inhibiting NO synthase and guanylate cyclase. Platelet aggregation
      to ADP and collagen was evaluated in Platelet-Rich Plasma (PRP) in the presence
      of a 6-min incubation with D-glucose and mannitol, both without and with LY379196
      and the guanylate cyclase inhibitor (H-[1,2,4]Oxadiazolo [4,3-a]quinoxaline-1
      one)(ODQ). Iso-osmolar concentrations of D-glucose, mannitol, L-glucose and
      fructose, and PMA increased NO production (p=0.0001). Effects of D-glucose and
      mannitol were blunted by LY379196. D-glucose and mannitol enhanced platelet cGMP
      and cAMP (p=0.0001) with a mechanism blunted by NO synthase and guanylate-cyclase
      inhibition, but did not modify platelet aggregation. In conclusion, glucose
      activates the NO/cyclic nucleotide pathway in human platelets with an osmotic
      mechanism mediated by PKC-beta.

PMID- 15735805
TI  - Effects of aspirin, clopidogrel and dipyridamole administered singly and in
      combination on platelet and leucocyte function in normal volunteers and patients
      with prior ischaemic stroke.
AB  - The aim of this study was to assess whether triple antiplatelet therapy is
      superior to dual and mono therapy in attenuating platelet and leucocyte function.
      Aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and
      in various combinations (A, C, D, AC, AD, CD, ACD), each for two weeks (without
      washout) to 11 healthy subjects and to 11 patients with previous ischaemic stroke
      in two randomised multiway crossover trials. At the end of each two-week period
      platelet aggregation, platelet-leucocyte conjugate formation and leucocyte
      activation were measured ex vivo blinded to treatment. Platelets were stimulated
      with collagen; additional measurements were made with adenosine diphosphate
      (ADP), platelet activating factor (PAF), adrenaline and the combination of, ADP,
      PAF and adrenaline. Results show that in the presence of collagen, ACD was
      superior to all antagonists or combinations, except AC, in reducing aggregation,
      platelet-leucocyte conjugate formation, and monocyte activation (all p<0.05). ACD
      was also more potent than other treatments, except AC, in inhibiting the
      aggregation and platelet-monocyte conjugate formation induced by the combination
      of ADP, PAF and adrenaline. The effects were similar in both volunteers and
      stroke patients. No serious adverse events or major bleeding events occurred.
      Triple antiplatelet therapy did not appear to be more effective than combined
      aspirin and clopidogrel in moderating platelet and leucocyte function. Any
      additional clinical benefit provided by dipyridamole may be through other
      mechanisms of action.

PMID- 15735806
TI  - Nitroaspirin plus clopidogrel versus aspirin plus clopidogrel against platelet
      thromboembolism and intimal thickening in mice.
AB  - Clopidogrel plus aspirin is the treatment of choice for patients undergoing
      percutaneous, coronary interventions with stenting, but it does not prevent
      restenosis. NCX-4016, a nitric oxide-releasing aspirin (nitroaspirin), exerts a
      wider range of antiplatelet actions compared to aspirin, superior antithrombotic
      activity and reduces restenosis after arterial injury in animals. The aim of the
      present study was to compare the combination of nitroaspirin plus clopidogrel
      with aspirin plus clopidogrel in a model of platelet pulmonary thromboembolism,
      bleeding and intimal thickening in mice. Drugs were administered orally for 5
      days; the antithrombotic effects were evaluated against collagen plus epinephrine
      induced pulmonary thromboembolism, the haemorrhagic effects by tail transection
      bleeding time and the effects on neointima proliferation by histomorphology of
      photochemically injured femoral arteries. Lung platelet emboli were reduced
      significantly and more effectively by nitroaspirin plus clopidogrel (-56%, p<0.05
      vs control) than by aspirin plus clopidogrel (-26%, p<0.05 vs control). Ex vivo
      platelet aggregation was inhibited maximally by nitroaspirin plus clopidogrel.
      Aspirin plus clopidogrel strikingly prolonged the bleeding time while
      nitroaspirin plus clopidogrel induced a lesser prolongation. Nitroaspirin plus
      clopidogrel significantly reduced intimal thickening of the femoral artery while
      aspirin plus clopidogrel was ineffective. Nitroaspirin plus clopidogrel is more
      effective and less prohaemorrhagic than aspirin plus clopidogrel in mice;
      provided these data are confirmed in other animal models, nitroaspirin plus
      clopidogrel may represent a new regimen to be tested in patients undergoing
      coronary revascularization procedures.

PMID- 15735807
TI  - The Fc gammaRIIa polymorphism R/H131, autoantibodies against the platelet
      receptors GPIb alpha and Fc gammaRIIa and a risk for thromboembolism in lupus
      anticoagulant patients.
AB  - There is a clear propensity of individuals with lupus anticoagulant (LA) for
      thromboembolic disease (TE). Yet, it is not clear how individuals at risk for TE
      can be differentiated from those who are not. The Fc gammaRIIa receptor is the
      only Fc receptor expressed by platelets. As platelets can be activated via this
      receptor, we have compared gene frequencies of the Fc gammaRIIa polymorphism
      R/H131 in 46 and 27 patients with (LA/TE+) and without TE (LA/TE-), respectively,
      in an exploratory study. Furthermore, we investigated the presence of
      autoantibodies against Fc gammaRIIa and/or GPIb alpha, which is in close
      proximity to the Fc gammaRIIa and interacts with it functionally, and a possible
      linkage of antibody formation to HLA class II alleles. The Fc gammaRIIa-R/R131
      genotype was significantly less frequent in patients with LA compared to controls
      (p<0.025). These findings were due to an increased frequency of heterozygous
      patients in the LA/TE+ cohort (odds ratio 6.76, 95% confidence interval 1.55
      62.03, p<0.008). For the first time, heterozygosity, rather than homozygosity,
      can be linked to disease, which may be explained by the dual function of the Fc
      gammaRIIa, namely binding of antibodies to platelets and thereby their
      activation, and, on the other hand, clearance of antibody coated platelets by the
      phagocyte system. There was no correlation between the presence of anti-Fc
      gammaRIIa or anti-GPIb alpha autoantibodies and the Fc gammaRIIa-R/H131
      polymorphism, nor the incidence of TE, nor HLA class II alleles.

PMID- 15735808
TI  - Variability in clinical laboratory practice in testing for disorders of platelet
      function: results of two surveys of the North American Specialized Coagulation
      Laboratory Association.
AB  - Disorders of platelet function are important causes of abnormal bleeding that
      require laboratory tests for diagnosis. Currently there are limited guidelines on
      how to perform clinical testing for these disorders. The goal of our study was to
      obtain information on how disorders of platelet function are currently evaluated
      in clinical laboratories. Two patterns-of-practice surveys were distributed to
      laboratories of the North American Specialized Coagulation Laboratory Association
      (NASCOLA). The information collected was analyzed to determine practices and
      common problems. Forty-seven NASCOLA laboratories participated and 54% completed
      both surveys. The majority of the laboratories that responded performed more than
      50 aggregation tests per year, mainly using platelet rich plasma based
      methodologies. A minority performed testing for platelet secretion and dense
      granule abnormalities. While platelet aggregation results were reviewed in
      various ways, laboratories most commonly issued a combined report containing
      quantitative values (% aggregation and/or slope) and a qualitative
      interpretation. Although laboratories used similar agonists for aggregation
      testing, the final agonist concentrations varied widely. Several approaches were
      also used to obtain reference intervals. Comments offered by the participants
      indicated that performing, and interpreting platelet function tests were
      challenging for many clinical laboratories. Although common practices have
      evolved, there is considerable variability in the diagnostic test procedures used
      by clinical laboratories to evaluate disorders of platelet function. These
      patterns-of-practice surveys illustrate a need for guidelines and recommendations
      for clinical laboratories performing tests of platelet function.

PMID- 15735809
TI  - Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after
      induced release of von Willebrand factor during acute systemic inflammation.
AB  - Von Willebrand factor (VWF) is synthesized in endothelial cells, stored in the
      form of high molecular weight multimers and released after stimulation. After
      release, the multimers are cleaved by ADAMTS13 (von-Willebrand-factor-cleaving
      protease). We studied healthy volunteers in a double-blind, placebo controlled
      inflammation model. Ten male volunteers received 2 ng/kg endotoxin intravenously,
      and 5 volunteers placebo. Endotoxin infusion induced systemic inflammation and
      coagulation activation. After 4 hours the observed increase in neutrophils
      reached a maximum (273+/-34% of baseline; mean+/-SEM) and the platelet count
      dropped (81+/-2%). These parameters returned to baseline values after 24 hours.
      VWF antigen increased to 259+/-16% of baseline after 4 hours, remained elevated
      (192+/-15%) after 24 hours and returned to baseline after 7 days. Unusually large
      VWF multimers occurred in the plasma 4 hours after endotoxin infusion. ADAMTS13
      activity (measured with a collagen-binding assay) decreased to 64+/-5% of
      baseline (P<0.001) after 4 hours, was still reduced after 24 hours (86+/- %;
      P=0.008) and returned to normal after 7 days. VWF multimer analysis showed
      pronounced satellite bands in the 4-hour samples, indicating cleavage of VWF by
      ADAMTS13. No apparent changes of the analyzed parameters were observed in the
      placebo group. The reciprocal course of ADAMTS13 and VWF after short-term VWF
      release induced by systemic inflammation is similar to that observed after
      induction of VWF release by desmopressin.

PMID- 15735810
TI  - Adhesion molecules and cardiovascular risk in peripheral arterial disease.
      Soluble vascular cell adhesion molecule-1 improves risk stratification.
AB  - Although intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion
      molecule-1 (VCAM-1) play a relevant role in atherosclerosis, little is known
      about the prognostic impact of their soluble forms (s) in patients with
      peripheral arterial disease (PAD). The aim of this prospective study was to
      verify whether plasma levels of sICAM-1 and sVCAM-1 predict cardiovascular risk
      in PAD, and improve the prognostic value of the ankle/brachial index (ABI) alone.
      Accordingly, plasma levels of sICAM-1 and sVCAM-1, and the ABI were measured in
      75 PAD patients who were monitored for a mean of 24+/-13 months. Twenty-two
      (29.3%) patients had a cardiovascular event (15 coronary, 3 cerebrovascular and 4
      peripheral events). Plasma levels of sVCAM-1 were 618+/-258 ng/mL in patients
      with and 496+/-164 ng/mL in those without an event (p=0.016). The corresponding
      sICAM-1 values were 344+/-239 ng/mL and 275+/-99 ng/mL (p=0.079). The
      cardiovascular event rate was higher in patients with sVCAM-1 levels above the
      median than in those with sVCAM-1 below the median (p=0.0027 by log rank test).
      Independent predictors of events were sVCAM-1 levels above the median (p=0.005)
      and an ABI below the median (p=0.001). Amongst patients with ABI below the
      median, the occurrence of sVCAM-1 above the median was associated with a 3.4-fold
      increase in risk (95% CI 1.308 to 9.573, p=0.013). In conclusion, increased
      plasma levels of sVCAM-1 have a negative prognostic impact in PAD and improve the
      predictive value of ABI, which is currently the most powerful risk indicator in
      these patients.

PMID- 15735811
TI  - -455G/A polymorphism and preprocedural plasma levels of fibrinogen show no
      association with the risk of clinical restenosis in patients with coronary stent
      placement.
AB  - The effect of preprocedural fibrinogen levels on in-stent restenosis is largely
      unknown. The -455G/A polymorphism of the fibrinogen beta-gene is associated with
      baseline plasma level or acute phase increase of fibrinogen. Therefore, we
      hypothesized that there is a relationship between this polymorphism and
      preprocedural fibrinogen level and clinical restenosis at follow-up among
      patients with coronary stent placement. The GENetic DEterminants of Restenosis
      (GENDER) project is a multicenter follow-up study that enrolled 3,146 consecutive
      patients after successful percutaneous coronary intervention. A coronary stent
      was placed in 2,309 patients. Of these, 2,257 (97.7%) patients were successfully
      genotyped for the -455G/A polymorphism. Plasma fibrinogen levels were measured at
      baseline in a subpopulation of 623 stented patients with the von Clauss method
      and patients were grouped into tertiles according to fibrinogen levels. Primary
      endpoint was target vessel revascularization (TVR); secondary combined endpoint
      was defined as death presumably from cardiac causes, MI not attributable to
      another coronary artery than the target vessel, and TVR. No association was
      observed between the -455G/A polymorphism and TVR or combined endpoint (p=0.99,
      p=0.97, respectively). Multivariate regression analysis revealed that the risk of
      TVR and combined endpoint was not higher for patients in the highest tertile for
      fibrinogen versus the lowest tertile (RR=0.60, 95% CI: 0.26-1.37 for TVR,
      RR=0.64, 95% CI: 0.29-1.44 for combined endpoint). In conclusion, the presence of
      -455G/A polymorphism in the fibrinogen beta-gene and preprocedural fibrinogen
      level is not associated with an increased risk of TVR or combined endpoint in a
      patient population with coronary stent placement. Therefore, these parameters are
      not worthwhile for stratifying patients at risk for restenosis pre-stenting.

PMID- 15735812
TI  - Contribution of haplotypes across the fibrinogen gene cluster to variation in
      risk of myocardial infarction.
AB  - Fibrinogen has consistently been recognized as an independent predictor of
      myocardial infarction (MI). Multiple mechanisms link fibrinogen to MI; therefore
      disentangling the factors underlying variation in plasma fibrinogen concentration
      is essential. Candidate regions in the fibrinogen gamma (FGG), alpha (FGA) and
      beta (FGB) genes were screened for single nucleotide polymorphisms (SNPs).
      Several novel SNPs were detected in the FGG and FGA genes in addition to the
      previously known SNPs in the fibrinogen genes. Tight linkage disequilibrium
      extending over various physical distances was observed between most SNPs.
      Consequently, eight SNPs were chosen and determined in 377 postinfarction
      patients and 387 healthy individuals. None of the SNPs were associated with
      plasma fibrinogen concentration or MI. Haplotype analyses revealed a consistent
      pattern of haplotypes associated with variation in risk of MI. Of the four
      haplotypes inferred using the FGA -58G>A and FGG 1299 +79T>C SNPs, the most
      frequent haplotype, FGG-FGA*1 (prevalence 46.6%), was associated with increased
      risk of MI (OR 1.51; 95%CI 1.18, 1.93), whereas the least frequent haplotype, FGG
      FGA*4 (11.8%), was associated with lower risk of MI (OR 0.79 95%CI 0.64, 0.98).
      In conclusion, fibrinogen haplotypes, but not SNPs in isolation, are associated
      with variation in risk of MI.

PMID- 15735813
TI  - Soluble CD40L in peripheral artery disease. Relationship with disease severity,
      platelet markers and the effects of angioplasty.
AB  - Although soluble CD40L (sCD40L, possibly derived from platelets and pro
      inflammatory in vitro) may be implicated in thrombosis and haemostasis, there are
      little data in peripheral artery disease (PAD). We hypothesised the following:
      (a) that sCD40L relates to the clinical severity of PAD; and (b) that peripheral
      artery angioplasty acutely raises sCD40L levels. sCD40L was compared to
      established platelet markers soluble P selectin, platelet microparticles and
      platelet surface expression of CD62 and CD63. We recruited 36 healthy controls,
      33 patients with intermittent claudication (IC), and 33 with symptomatically more
      severe critical limb ischaemia (CLI), measuring plasma markers by ELISA and
      membrane markers by flow cytometry. Eleven patients with CLI subsequently
      underwent peripheral artery angioplasty: blood was taken before and 10 minutes
      after the intervention. Results show that sCD40L was raised in IC at median 68
      (IQR 28-333) pg/ml and in CLI at 64 (34-282) pg/mL compared to 35 (IQR 28-55)
      pg/ml in the healthy controls (p=0.009). Levels were no different between IC and
      CLI. The same distribution pattern was present for soluble P selectin, %platelets
      CD62+ve and CD63+ve. sCD40L failed to correlate significantly with ABPI
      (p=0.264), unlike %platelets CD62+ve (p=0.0032) and CD63+ve (p=0.009). Pre
      angioplasty sCD40L level of 72 (35-610) ng/ml rose to 100 ng/ml (IQR=60
      237)(p=0.018) post-angioplasty. Plasma sCD40L, in addition to other platelet
      indices, is raised in peripheral atherosclerosis and is increased by peripheral
      artery angioplasty, although levels seem unrelated to clinical severity. Failure
      to correlate with other markers suggest the platelet may not be the sole source
      of sCD40L, and that other cells may contribute to plasma levels.

PMID- 15735814
TI  - The alkylating carcinogen N-methyl-N'-nitro-N-nitrosoguanidine activates the
      plasminogen activator inhibitor-1 gene through sequential phosphorylation of p53
      by ATM and ATR kinases.
AB  - The alkylating agent MNNG is an environmental carcinogen that causes DNA lesions
      leading to cell death. We previously demonstrated that MNNG induced the
      transcriptional activity of the plasminogen activator inhibitor-1 (PAI-1) gene in
      a p53-dependent manner. However, the mechanism(s) linking external MNNG
      stimulation and PAI-1 gene induction remained to be elucidated. Here, we show
      that ATM and ATR kinases, but not DNA-PK, which participate in DNA damage
      activated checkpoints, regulate the phosphorylation of p53 at serine 15 in
      response to MNNG cell treatment. Using ATM-deficient cells, ATM was shown to be
      required for early phosphorylation of serine 15 in response to MNNG, whereas
      catalytically inactive ATR selectively interfered with late phase serine 15
      phosphorylation. In contrast, DNA-PK-deficient cells showed no change in the MNNG
      induced serine 15 phosphorylation pattern. In agreement with this, sequential
      activation of ATM and ATR kinases was also required for adequate induction of the
      endogenous PAI-1 gene by MNNG. Finally, we showed that cells derived from PAI-1
      deficient mice were more resistant to MNNG-induced cell death than normal cells,
      suggesting that p53-dependent PAI-1 expression partially mediated this effect.
      Since PAI-1 is involved in the control of tumor invasiveness, our finding that
      MNNG induces PAI-1 gene expression via ATM/ATR-mediated phosphorylation of p53
      sheds new insight on the role of these DNA damage-induced cell cycle checkpoint
      kinases.

PMID- 15735815
TI  - Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of
      cancer-related venous thromboembolism.
AB  - Although extended secondary prophylaxis with low-molecular-weight heparin was
      recently shown to be more effective than warfarin for cancer-related venous
      thromboembolism, its cost-effectiveness compared to traditional prophylaxis with
      warfarin is uncertain. We built a decision analytic model to evaluate the
      clinical and economic outcomes of a 6-month course of low-molecular-weight
      heparin or warfarin therapy in 65-year-old patients with cancer-related venous
      thromboembolism. We used probability estimates and utilities reported in the
      literature and published cost data. Using a US societal perspective, we compared
      strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The
      incremental cost-effectiveness ratio of low-molecular-weight heparin compared
      with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a
      quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars.
      Overall, 46% (7108 dollars) of the total costs associated with low-molecular
      weight heparin were attributable to pharmacy costs. Although the low-molecular
      weigh heparin strategy achieved a higher incremental quality-adjusted life
      expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical
      benefit was offset by a substantial cost increment of 7,609 dollars. Cost
      effectiveness results were sensitive to variation of the early mortality risks
      associated with low-molecular-weight heparin and warfarin and the pharmacy costs
      for low-molecular-weight heparin. Based on the best available evidence, secondary
      prophylaxis with low-molecular-weight heparin is more effective than warfarin for
      cancer-related venous thromboembolism. However, because of the substantial
      pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US,
      this treatment is relatively expensive compared with warfarin.

PMID- 15735816
TI  - "ProC Global": a functional screening test that predicts recurrent venous
      thromboembolism.
AB  - Abnormalities of the Protein C (PC) pathway are found in the majority of patients
      with thrombophilia. ProC Global is a coagulation assay that reflects the net
      effect of the PC pathway by measuring the activated partial thromboplastin time
      (APTT) of patient and control plasma, before and after activation of endogenous
      PC by Protac, a snake venom. Previous studies have suggested that abnormalities
      in this test are associated with an increased risk of venous thromboembolism
      (VTE). A retrospective analysis was performed using frozen plasma samples from
      140 patients with confirmed VTE to determine whether an abnormal ProC Global
      result (in the presence and in the absence of known abnormalities in the PC
      pathway) is a predictor of initial and recurrent VTE. Patients were tested for
      the presence of activated protein C resistance, Factor V Leiden, PC and protein S
      (PS) deficiency, and non-specific inhibitor positivity. Mean ProC Global results
      were significantly lower in patients with recurrent VTE than in patients without
      recurrent VTE. The association between abnormal ProC Global result and recurrent
      VTE showed a strong trend, before (odds ratio, OR 3.6) and after (OR 3.1)
      exclusion of known thrombophilic abnormalities. Patients with a first episode of
      idiopathic VTE also expressed significant lower ProC Global results than those
      with secondary VTE. After exclusion of known PC pathway abnormalities, there was
      a statistically significant association between abnormal ProC Global and initial
      idiopathic VTE (p=0.04). These results suggest that ProC Global may serve as a
      predictor of recurrent VTE and potentially for first episode of idiopathic VTE.
      ProC Global may help identify patients at increased risk of initial and recurrent
      VTE.

PMID- 15735817
TI  - Effect of age on the performance of a diagnostic strategy based on clinical
      probability, spiral computed tomography and venous compression ultrasonography:
      the ESSEP study.
AB  - As the prevalence of PE increases with age, the effect of age on the diagnostic
      work-up in front of a clinical suspicion of PE deserves exploration. In this
      retrospective analysis, we used the data from 1041 consecutive suspected PE
      patients. The patients were divided into three groups according to tertiles of
      age: under 54 years, 54 to 73 years and above 73 years. The prevalence of PE in
      patients with respectively low, intermediate and high pretest clinical
      probability was expressed within each age group. We studied the effect of age on
      the results observed in three main groups of patients, after performing CT scan
      and ultrasonography (CUS): (1) patients with inconclusive results; (2) patients
      with negative findings on both exams and non high pretest clinical probability;
      (3) patients with positive findings.The prevalence of PE increased significantly
      with age, in overall, as well as in patients with low or intermediate pretest
      clinical probability. An analysis according to the three main diagnostic groups
      showed that: (1) the distribution of inconclusive spiral CT or CUS examinations
      was not different between age groups; (2) no thromboembolic event occurred in
      untreated patients with low or intermediate clinical probability aged under 54
      years of age, whereas 7 events were diagnosed in patients aged over 73 years
      (p<0.001); (3) a higher proportion of older patients had a positive result at
      both spiral CT and CUS examinations. The percentage of positive CT scans in the
      case of negative or inconclusive CUS results was not different between age
      groups; conversely, in the case of a negative or inconclusive CT scan, the
      percentage of positive CUS was higher in older patients. In conclusion,
      management of elderly suspected PE patients appears to be different from both the
      work-up and the outcome perspectives.

PMID- 15735818
TI  - High frequency of premature termination mutations in the factor V gene: three
      factor V deficiency case reports and a mutation review.

PMID- 15735819
TI  - Familial hypodysfibrinogenaemia associated with second occurrence of gamma326 Cys
      ->Tyr mutation.

PMID- 15735820
TI  - Gly392Cys missense mutation in the A2 domain of factor V causing severe factor V
      deficiency: molecular characterization by expression of the recombinant protein.

PMID- 15735821
TI  - Is homozygosity for factor V Leiden a risk factor for myocardial infarction in
      young women who smoke?

PMID- 15735822
TI  - Nocturnal rise of urinary thromboxane B 2 in patients with coronary artery
      disease.

PMID- 15735824
TI  - Rebuttal: A problem of calibration in the paper 'Point of care monitoring of oral
      anticoagulant therapy in children'.

PMID- 15735823
TI  - Different effects of low-dose transdermal and oral oestrogen therapy on
      procarboxy-peptidase U, an inhibitor of fibrinolysis, in healthy postmenopausal
      women: a randomised, placebo-controlled study.

PMID- 15735827
TI  - Are cephalosporins appropriate for the treatment of acute otitis media in this
      era of increasing antimicrobial resistance among common respiratory tract
      pathogens?

PMID- 15735828
TI  - Neonatal asymmetric crying facies: a new look at an old problem.
AB  - Neonatal asymmetric crying facies, described 75 years ago, is a clinical
      phenotype resembling unilateral partial peripheral facial nerve paralysis, with
      an incidence of approximately 1 per 160 live births. The cause is either facial
      nerve compression or faulty facial muscle and/or nerve development. Spontaneous
      resolution is expected with the former, but not necessarily with the latter
      etiology. Approximately 10% of the developmental cases have associated major
      malformations. Mandibular asymmetry and maxillary-mandibular asynclitism (non
      parallelism of the gums) are frequently overlooked visual clues to nerve
      compression. Ultrasound imaging of facial muscles and electrodiagnostic testing
      may be useful for differential diagnosis and management.

PMID- 15735829
TI  - Psychiatric symptoms of adolescents with physical complaints admitted to an
      adolescence unit.
AB  - SUMMARY: The aim of this study was to evaluate the psychiatric symptoms among
      adolescents who were seen in the outpatient clinic for their physical complaints.
      Two hundred and ninety adolescent outpatients (154 males and 136 females) between
      13 and 17 years of age (mean 14.3+/-1.2) are included in this study. Patients
      with known psychiatric disorders, mental retardation, organic brain diseases, or
      chronic organic problems were excluded. The Brief Symptom Inventory, which
      measures the psychiatric symptoms under the categories of anxiety, depression,
      negative self, somatization, and hostility, was given to all subjects. Symptoms
      of urinary and cardiovascular systems were related to hostility. Patients with
      obesity, hirsutism, problems of external genitalia, enuresis nocturna, abdominal
      pain, chest pain, and lack of weight gain showed psychiatric symptoms at
      pathological levels. Hostility symptom was found to be high in all groups.

PMID- 15735830
TI  - Conservative approach to the mediastinitis in childhood secondary to esophageal
      perforation.
AB  - The aim of this study was to evaluate the safety and efficacy of nonoperative
      treatment of esophageal perforation (EP) in children. Between 1999 and 2004, 13
      episodes in 12 patients were evaluated. The treatment program consisted of broad
      spectrum antibiotics, nasopharyngeal aspiration, parenteral and/or enteral
      nutrition by gastrostomy, and pleural effusion or mediastinal abscess drainage
      when required. Mean age of the patients was 3.75 +/- 1.13 (range 3-7 years). Two
      patients (16.7%) were girls and 10 patients (83.3%) were boys. Chest pain was
      found 76.9% of all EP episodes (10 of 13 perforations), followed by dyspnea in
      69.2% (9 of 13), vomiting in 46.1% (6 of 13), fever in 46.1% (6 of 13), and
      epigastric pain in 7.6% (1 of 13). No deaths occurred. In children, in contrast
      with the adults, EP can be treated safely by nonoperative methods.

PMID- 15735831
TI  - Undetected hepatomegaly in obese children by primary care physicians: a pitfall
      in the diagnosis of pediatric nonalcoholic fatty liver disease.
AB  - The diagnostic evaluation of nonalcoholic fatty liver disease (NAFLD) relies on
      the initial detection of hepatomegaly or elevated serum aminotransferases by the
      primary care provider. In this investigation, the aptitude of the primary care
      provider to identify children with hepatomegaly and initiate an evaluation for
      NAFLD is determined. The physical examination findings and requests for
      diagnostic testing of 18 primary care physicians (and pediatric
      gastroenterologists) on 11 obese school-aged children, including a subset of
      children with hepatomegaly and NAFLD, were analyzed. In children with NAFLD,
      clinicians detected hepatomegaly in 1.4% of encounters and requested serum liver
      chemistries in 12.5% of encounters. Hepatomegaly is detected poorly in obese
      children by primary care physicians and thereby increases the likelihood of a
      delayed or omitted evaluation for NAFLD.

PMID- 15735832
TI  - A bioethical analysis of a form of psychologic abuse: teaching hatred to
      children.

PMID- 15735833
TI  - Adolescent and adult issues in CHARGE syndrome.
AB  - Very little information has been published about adolescents and older
      individuals with Coloboma, Heart defects, Atresia choanae, Retarded growth and
      development, Genital hypoplasia, Ear anomalies and deafness (CHARGE) syndrome.
      This paper describes the results of a study that identifies the unique issues
      faced by adolescents and adults with CHARGE. Descriptive information was gathered
      from parents of patients with CHARGE, and/or the patients themselves, about their
      developmental, medical, educational, and social history. The resulting body of
      information provides important insights into the prognosis and special needs of
      individuals with CHARGE, as well as further research questions.

PMID- 15735835
TI  - Congenital and infantile nephrotic syndrome in Thai infants.
AB  - Congenital and infantile nephrotic syndrome reported from the Eastern world is
      rare and might be a different entity from that in the West. In a retrospective
      review of 10 nephrotic syndrome in Thai infants (5 girls and 5 boys), 7 were
      diagnosed with congenital nephrotic syndrome and 3 with infantile nephrotic
      syndrome. Two had congenital nephrotic syndrome secondary to congenital syphilis.
      All had edema, ascites, and failure to thrive. Of the 3 patients tested for
      thyroid function, all showed hypothyroidism. Two patients developed renal
      failure. Renal tissue was examined from 4 patients from 3 biopsies and 2
      autopsies; only 1 patient showed tubular microcysts. Symptomatic therapy was
      performed concurrently with penicillin therapy in 2 patients having congenital
      syphilis. Prednisolone, cyclophosphamide, captopril, and enalapril were tried in
      some patients, with little effect. Five patients died from respiratory failure
      complicated by later infection, 1 patient died from renal failure, and 4 patients
      were lost to follow-up. Nephrotic syndrome in the first year of life in the
      Eastern world is rare. Prognosis of nephrotic syndrome in Thai infants at this
      time is still poor.

PMID- 15735834
TI  - Mothers' help-seeking for pediatric psychosocial problems.
AB  - Pediatricians have been criticized for failing to identify psychosocial problems
      in their pediatric patients. Maternal disclosure is important for identification;
      however, many mothers fail to discuss their concerns with the pediatrician. The
      present study explored the hypothesis that mothers are seeking and receiving help
      from sources other than the pediatrician. Participants were 50 mothers who
      brought their 4-13-year-old child for a routine health supervision visit at a
      county-funded hospital serving primarily low-income families. Results indicated
      that mothers actively seek help from multiple sources and find the help they
      receive useful. Clinical implications of these findings are discussed.

PMID- 15735836
TI  - Fatal stroke in a child with severe iron deficiency anemia and multiple
      hereditary risk factors for thrombosis.

PMID- 15735837
TI  - Pulmonary actinomycosis masquerading as a malignant lung tumor in a 9-year-old
      boy.

PMID- 15735838
TI  - Failure to thrive.

PMID- 15735839
TI  - Raising the bar: a primer on evidence-based decision-making.

PMID- 15735840
TI  - Fast-track cardiac anesthesia: choice of anesthetic agents and techniques.
AB  - Fast-track cardiac anesthesia (FTCA) incorporates early tracheal extubation,
      decreased length of intensive care unit (ICU) and hospital stay, and (ideally)
      should avoid or reduce complications to safely achieve cost-savings. A growing
      body of evidence from randomized trials has identified many anesthetic
      interventions that can improve outcome after cardiac surgery. These include new
      short-acting hypnotic, opioid, and neuromuscular blocking drugs. An effective
      FTCA program requires the appropriate selection of suitable patients, a low-dose
      opioid anesthetic technique, early tracheal extubation, a short stay in the ICU,
      and coordinated perioperative care. It is also dependent on the avoidance of
      postoperative complications such as excessive bleeding, myocardial ischemia, low
      cardiac output state, arrhythmias, sepsis, and renal failure. These complications
      will have a much greater adverse effect on hospital length of stay and healthcare
      costs. A number of clinical trials have identified interventions that can reduce
      some of these complications. The adoption of effective treatments into clinical
      practice should improve the effectiveness of FTCA.

PMID- 15735841
TI  - Applied neuromonitoring in cardiac surgery: patient specific management.
AB  - Various studies have demonstrated that over 50% of patients presenting for
      coronary revascularization surgery have evidence of extracranial or intracranial
      atherosclerotic disease. Although evidence is compelling that cerebral emboli are
      a major cause of perioperative central nervous system (CNS) morbidity in such
      patients, it is also apparent that alterations in cerebral perfusion pressure and
      blood flow can profoundly influence the extent of injury after an embolic insult.
      In this context, the recent studies demonstrating improved CNS outcomes with
      applied neuromonitoring in cardiac surgical patients can be understood as
      reflecting the optimization of CNS perfusion characteristics with potential
      amelioration of microembolic injury. This review critically evaluates and
      discusses the relevant characteristics of applied neuromonitoring techniques,
      including bispectral index (BIS), transcranial Doppler (TCD), and near infrared
      reflectance spectroscopy (NIRS) in the context of patients undergoing cardiac
      surgical procedures. Recent outcomes data regarding CNS and related morbidity and
      the influence of neuromonitoring in these groups are evaluated.

PMID- 15735842
TI  - The impact of intraoperative echocardiography on clinical outcomes following
      adult cardiac surgery.
AB  - Over the past 30 years, intraoperative echocardiography has become an invaluable
      diagnostic tool and monitor of cardiac performance for the management of cardiac
      surgical patients. The essential information provided by intraoperative
      echocardiography regarding hemodynamic management, cardiac valve function,
      congenital heart lesions, and great vessel pathology has contributed to its
      widespread popularity. Numerous investigations have been conducted in an attempt
      to specifically demonstrate a beneficial impact of intraoperative
      echocardiography in cardiac surgery. However, there is a relative paucity of data
      derived from prospective trials in which the use of intraoperative
      echocardiography has been randomized among various cardiac surgical patient
      populations to formally ascertain, rather than simply infer, its putative impact
      on perioperative decision-making and clinical outcomes. Ironically, the
      popularity of intraoperative echocardiography has imposed ethical limitations on
      performing randomized trials in patient populations for whom significant benefit
      has been previously inferred. Nonetheless, significant evidence has been
      published to support its almost universal acceptance as an important
      perioperative diagnostic tool and monitor for cardiac surgical patients. This
      review focuses on the impact of intraoperative echocardiography on clinical
      outcomes in the more common adult cardiac surgical scenarios, including coronary
      artery bypass graft surgery, mitral and aortic valve surgery, and in evaluating
      the intrathoracic aorta.

PMID- 15735843
TI  - Evidence based coagulation monitors: heparin monitoring, thromboelastography, and
      platelet function.
AB  - The hemostatic management of patients undergoing cardiac surgery is a unique
      challenge. Since its inception, cardiopulmonary bypass (CPB) has required
      meticulous attention to maintaining adequate anticoagulation. New anticoagulants
      and alternative monitoring techniques present an opportunity to investigate
      potential advances in the area of anticoagulation for CPB. Hemostasis after CPB
      is still a vexing problem, and the addition of antiplatelet medication to the
      platelet defect already incurred during CPB has led to hemorrhagic complications
      in cardiac surgery. The two opposing processes of anticoagulation and hemostasis
      must be managed carefully and modified with respect to the patient's hematologic
      status and desired hemostatic outcome. Cardiac surgical patients consume a much
      larger fraction of perioperative blood transfusions than the percentage of the
      surgical population they represent. Thus, during CPB, careful attention must be
      paid to optimal anticoagulation, platelet quiescence, biocompatible circuitry and
      interventions, and to monitoring hemostasis. The multifactorial etiology of the
      CPB-induced hemostatic defect requires a multimodal approach to blood
      conservation and hemostasis monitoring, including heparin maintenance and
      sophisticated point-of-care hemostasis monitoring. Each technology has its own
      attributes and each may be suitable for different populations based upon the
      expected defects being measured. This article reviews the evidence supporting the
      use of point-of-care monitors in coagulation and hemostasis management in cardiac
      surgical patients.

PMID- 15735844
TI  - The safety and efficacy of "bloodless" cardiac surgery.
AB  - Nearly 20% of blood transfusions in the United States are associated with cardiac
      surgery. Despite the many blood conservation techniques that are available, safe,
      and efficacious for patients undergoing cardiac surgery, many of these operations
      continue to be associated with significant amounts of blood transfusion. Although
      surgical bleeding after cardiopulmonary bypass is a common problem as reflected
      by the substantial use of blood products, it is the individual physician and
      institutional behavior that have been identified as reasons for transfusion and
      not necessarily patient comorbidity or blood loss. Transfusion rates in cardiac
      surgery remain high despite major advances in perioperative blood conservation,
      with large variations among individual centers. The adoption of available blood
      conservation techniques, either alone or in combination in patients undergoing
      cardiac surgery, could result in an estimated 75% reduction of unnecessary
      transfusions. The success of previously reported blood conservations programs in
      cardiac surgery should call for a reevaluation of allogeneic transfusion
      practices in patients undergoing cardiac surgery. By applying the numerous
      reported blood conservation strategies for the management of patients presenting
      for cardiac surgery, we can preserve our dwindling blood resources and help
      alleviate some of the direct costs of blood as well as the indirect costs of
      treating noninfectious and infectious complications of transfusion.

PMID- 15735845
TI  - Evidence-based renal protection in cardiac surgery.
AB  - Acute renal dysfunction is a common serious complication of cardiac surgery.
      Although a diversity of mechanisms exist by which the kidney can be damaged
      during cardiac surgery, atheroembolism, ischemia-reperfusion, and inflammation
      are believed to be primary contributors to perioperative renal insult. In
      addition, the high metabolic demands of active tubular reabsorption and the
      oxygen diffusion shunt characteristic of renal circulation make the kidney
      particularly vulnerable to ischemic injury. Remote effects of acute renal injury
      likely contribute to the strong association of this condition with other major
      postoperative morbidities and mortality and justify the search for renoprotective
      agents, even when dialysis is never required. Nonpharmacologic preventive
      strategies include procedure planning that is based on risk stratification,
      avoidance of nephrotoxins, and meticulous perioperative clinical care, including
      optimizing intravascular volume and attention to modifiable risk factors such as
      minimizing hemodilution. Although numerous pharmacologic interventions to prevent
      or treat acute renal injury have shown promise in animal models, randomized
      placebo-controlled clinical trials that have looked at measures of significant
      adverse outcomes such as death and dialysis have not confirmed a benefit.

PMID- 15735846
TI  - Atrial fibrillation after cardiac surgery: an evidence-based approach to
      prevention.
AB  - A number of advances in surgical and anesthetic techniques have reduced the risk
      for patients undergoing cardiac surgery. However, postoperative atrial
      fibrillation remains common, with an incidence ranging between 25% and 40%. It is
      associated with an increased incidence of congestive heart failure, renal
      insufficiency, and stroke that prolongs hospitalization and increases rates of
      readmission after discharge. Consequently, there has been great interest in
      strategies to prevent this arrhythmia. When both safety and efficacy are
      considered, the available evidence to date suggests that only beta-blockers can
      be recommended for the prevention of atrial fibrillation after cardiac surgery.
      Other treatments might be considered on an individual basis after careful
      consideration of the patient's potential for side effects.

PMID- 15735847
TI  - Regional anesthesia in cardiac surgery: a friend or a foe?
AB  - Escalating costs and change in the profile of patients presenting for cardiac
      surgery requires modification of perioperative management strategies. Regional
      anesthesia has played an integral part of many fast-track anesthesia protocols
      across North America and Europe. This review suggests that for patients
      undergoing coronary artery bypass graft surgery, the risk-to-benefit ratio is in
      favor of epidural and spinal anesthesia, provided there are no specific
      contraindications and the guidelines for the use of regional techniques in
      cardiac surgery are followed. Patients managed with regional techniques seem to
      benefit from superior postoperative analgesia, shorter postoperative ventilation,
      reduced incidence of supraventricular arrhythmia, and lower rates of
      perioperative myocardial infarction. The results of this analysis suggest that
      for each episode of neurologic complication, 20 myocardial infarctions and 76
      episodes of atrial fibrillation would be prevented, thus, we would consider the
      regional anesthesia and analgesia to be an effective strategy that improves
      perioperative morbidity. However, other treatment modalities such as the addition
      of calcium channel blockers, aspirin, and beating heart surgery, are also
      suggested to be beneficial in cardiac surgical patients and may impose less risk
      than the use of regional techniques. We believe that the results presented in
      this review are encouraging enough to permit continued investigation. A
      prospective, randomized, controlled multicenter trial needs to be adequately
      powered to answer important clinical questions and allow for a long-term follow
      up.

PMID- 15735848
TI  - Off pump coronary artery bypass graft surgery versus conventional coronary artery
      bypass graft surgery: a systematic review of the literature.
AB  - The recent development of off-pump coronary artery bypass (OPCAB) graft surgical
      techniques has led to numerous observational and several randomized trials that
      have investigated outcomes compared with the current gold standard of
      conventional on-pump coronary bypass (CCAB) graft surgery. This systematic review
      assesses the current randomized trials that compare OPCAB and CCAB. Numerous end
      points were investigated, including mortality, stroke, myocardial infarction,
      atrial fibrillation, blood transfusions, wound infections, and renal failure. In
      addition to these important outcomes, resource utilization markers were also
      examined such as hospital length of stay, intensive care unit length of stay, and
      duration of intubation/ventilation. Finally, when level I evidence from
      randomized trials was unavailable, level II evidence was examined. This was done
      for subgroup analysis, where currently no randomized trials exist, looking at
      OPCAB in high-risk patients. Recommendations were made as to who should receive
      OPCAB and the potential benefits in this patient population.

PMID- 15735849
TI  - ret/PTC and BRAF act as distinct molecular, time-dependant triggers in a sporadic
      Irish cohort of papillary thyroid carcinoma.
AB  - The purpose of this study was to assess BRAF mutation rates in various thyroid
      tissues and to investigate if concomitant mutations with ret/PTC activation
      occurred in inflammatory and neoplastic lesions. To this end, we developed a
      novel Taqman based screening assay for the common T1799A BRAF mutation.
      Heterozygous T1799A mutations were detected in 13 of 34 (44%) papillary thyroid
      carcinomas (PTCs) tested. No such mutations were detected in the other tissue
      types tested. Concomitant presence of both oncogenes was reported in 5 of the 34
      PTCs. A significant temporal trend was observed, with ret/PTC chimera detected
      for the most part before 1997 and BRAF mutations being more prevalent after 1997.
      The results suggest that some environmental/etiological agent(s) may have
      influenced the pathobiology of thyroid tumor development, among the population
      examined, over time.

PMID- 15735850
TI  - Loss of heterozygosity on chromosome 1 and 9 and hormone receptor analysis of
      metastatic malignant melanoma presenting in breast.
AB  - Malignant melanoma (MM), the most common metastatic solid tumor to involve the
      breast, may present as a diagnostic problem, frequently requiring the use of
      ancillary studies for accurate diagnosis. The implication of hormonal interplay
      is strong since metastatic MM to the breast is seen nearly always in women.
      However, the role of hormonal status as a predisposing factor in the development
      of this entity is largely unresolved. A number of chromosomal loci, including
      1p36 and 9p21-22, appear to harbor critical genes important to melanoma
      tumorigenesis, and additionally chromosome 9q22.3-31. We wanted to know if
      metastatic MM in breast showed chromosome 1p and 9p genetic alterations (loss of
      heterozygosity) similar to those that occur in primary cutaneous MM, and whether
      additional 9q LOH changes are present. Hormonal receptor status of the metastatic
      MM was also determined. We identified 20 patients with known MM metastatic to the
      breast, which we analyzed with the following genetic markers: D9S12 (9q22.3),
      D9S171 (9p21), IFNA (9p22), and D1S450 (1p). Visually directed microdissection
      was performed on archival histologic slides containing both tumor and adjacent
      normal breast epithelium, followed by single-step DNA extraction and polymerase
      chain reaction (PCR) amplification for evaluation of loss of heterozygosity (LOH)
      for the above-listed markers. Immunohistochemical (IHC) stains for estrogen
      receptor (ER) and progesterone receptor (PR) was performed on 10 of the cases.
      Twelve of the 20 cases contained DNA suitable for PCR amplification following
      direct visualization microdissection. Four of 8 (50%) informative cases showed
      LOH at 9p21 with D9S171. Ten cases were heterozygous for IFNA, with 2 cases (20%)
      showing LOH at this locus. These particular cases also showed LOH at 9p21. One of
      9 (11%) informative cases showed LOH for D1S450 (1p36). Five cases were
      heterozygous for D9S12, and 2 (40%) showed LOH in the tumor at 9q22.3. IHC stains
      for ER and PR were negative in the 10 tumors studied. Metastatic MM presenting as
      a breast mass is an interesting entity often requiring IHC studies for diagnosis,
      particularly when the histologic features simulate breast carcinoma or when no
      primary tumor is known. These tumors are ER and PR negative. Metastatic MM
      involving the breast shows similar genetic allelic losses on chromosome 9p21-22
      (50%) and 1p36 (11%), as previously described in primary cutaneous MM. Additional
      LOH was observed at the 9q22.3-31 locus (40%). We suggest this locus to be
      investigated for harboring potential genes important in the tumorigenesis of
      cutaneous MM.

PMID- 15735851
TI  - Divergent differentiation in malignant soft tissue neoplasms: the paradigm of
      liposarcoma and malignant peripheral nerve sheath tumor.
AB  - In tumors clonality does not always translate into morphologic uniformity. While
      most sarcomas exhibit only one line of histologic differentiation, a minority may
      display a strikingly diverse phenotype in addition to the main lineage. This
      phenomenon not only presents a diagnostic problem but also raises questions about
      the commitment of tumor cells toward a specific phenotype. Among sarcomas,
      malignant peripheral nerve sheath tumor (MPNST) and dedifferentiated liposarcoma
      are two entities in which divergent differentiation is a relatively frequent
      event. Diagnostically it is crucial to recognize the "primary" sarcoma in such
      tumors correctly and distinguish it from the "secondary" divergent elements. The
      presence of the latter could be the first morphologic clue to a specific sarcoma
      type. Even though it may be difficult to explain the pathogenesis of divergent
      differentiation, divergence still illustrates that the phenotype of a tumor cell
      is not set in stone but can be modulated or switched by a number of factors.

PMID- 15735852
TI  - Hurthle (oncocytic) cell tumors of thyroid: etiopathogenesis, diagnosis and
      clinical significance.
AB  - The etiopathogenesis and the classification of oncocytic (Hurthle cell) tumors of
      the thyroid is reviewed with an emphasis on the role played by mitochondrial and
      nuclear genetic abnormalities that interfere with mitochondrial function.
      Oxyphilia is classified into primary or secondary and the so-called Hurthle cell
      carcinoma is divided into oncocytic (Hurthle cell) variants of papillary and
      follicular carcinoma.

PMID- 15735853
TI  - Benign Hurthle cell adenoma with papillary architecture: a benign lesion
      mimicking oncocytic papillary carcinoma.
AB  - We studied the significance of encapsulated Hurthle cell thyroid nodules with
      papillary structures lacking the nuclear features of papillary thyroid carcinoma
      (PTC); 19 cases fulfilling these criteria were encountered The patients' ages
      ranged from 22 to 40 years (32+/-6), and the F:M ratio was 3:1 The tumors
      measured from 0.5-5 cm (2+/-1.1). The diameter of the tumor cell nuclei ranged
      from 5.6 to 7.2 microns. Many nodules had nuclei displaying a fine chromatin
      pattern somewhat resembling those of PTC, but these were present in <20% of the
      tumor cells. Immunohistochemically, there was reactivity for MIB-1 in the
      papillary structures, negativity to focally weak reactivity for HBME and galectin
      3, and negativity to moderate diffuse reactivity for CK19. Clinical follow-up
      from 1 to 19 years revealed no evidence of metastases in any of the cases. It is
      unlikely that the papillary structures in the study cases represent degenerative
      changes in view of the proliferative activity we have demonstrated in them. In
      view of (1) the encapsulation and the uniformity of the constituent cells, (2)
      the negative or weak immunoreactivity for galectin-3 and HBME and negative to
      moderate immunoreactivity for CK19, and (3) the absence or paucity of nuclear
      criteria for the diagnosis of PTC and the absence of lymph node metastasis in all
      study cases, we believe that these lesions represent the papillary variant of
      oncocytic follicular adenoma (Hurthle cell adenoma). Recognition of this entity
      is important to avoid an overdiagnosis of oncocytic PTC.

PMID- 15735854
TI  - Keratin-positive Ewing's sarcoma: an ultrastructural study of 12 cases.
AB  - Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) is an aggressive
      neoplasm of bone and soft tissue. Histologically, it is characterized by the
      presence of small round blue cells, which usually express MIC-2 and FLI-1
      immunohistochemically. The most specific feature for diagnosis, however, is
      cytogenetic or molecular evidence of a consistent abnormality, the
      t(11;22)(q24;q12), or variants thereof. The immunohistochemical expression of
      keratins in a significant proportion of these cases has been highlighted in
      several recent studies. The ultrastructural features of these keratin-positive
      tumors have not, however, been characterized in detail. In this study we analyzed
      the ultrastructural features of 12 well-documented EWS/PNETs that stained
      strongly for pankeratin by immunohistochemistry. Ultrastructurally, the tumor
      cells contained a few organelles, which included a small number of mitochondria,
      poorly developed Golgi complexes, free ribosomes, and inconspicuous rough
      endoplasmic reticulum. Rudimentary cell junctions were seen in 2 tumors while
      prominent junctions were observed in the remaining 10. Five tumors contained
      intracytoplasmic filaments, and definite tonofibrils were identified in 2. Well
      developed basal lamina around tumor cells were also demonstrated in 2 tumors.
      Follow-up information was available for all cases. Seven patients died of
      disease, 2 are alive with disease, and 3 have no current evidence of disease. The
      cohort includes 5 patients with a type-1 translocation, which has been associated
      with a better prognosis in some studies; 4 of these patients have died of their
      disease, and 1 is alive with recurrent disease. This study shows that keratin
      positive EWS/PNETs have evidence of epithelial differentiation ultrastructurally,
      and may possibly represent a more aggressive subset of the EWS/PNET group of
      tumors.

PMID- 15735855
TI  - Invasive micropapillary carcinoma of the breast: an immunohistochemical study of
      neoplastic and stromal cells.
AB  - A 59-year-old woman complained of a palpable mass in the right breast, and a
      needle biopsy disclosed small clusters of neoplastic cells in the fibrous stroma.
      The small clusters did not contain fibrovascular cores but exhibited
      micropapillary configuration. Epithelial membrane antigen (EMA)
      immunohistochemistry confirmed the reverse polarity of the neoplastic cells.
      Additionally, the plasma membrane of many neoplastic cells stained with E
      cadherin and beta-catenin. Myofibroblasts, which were positive for alpha smooth
      muscle actin (ASMA) and negative for cytokeratin 14, were abundant in the
      neoplastic stroma, but no CD34-positive stromal cells were observed in the
      neoplastic stroma. For comparison, 3 additional cases of invasive micropapillary
      carcinoma (IMC) and 4 cases of invasive ductal carcinoma (IDC) were studied.
      Similar results for stromal cells were obtained in all cases. Our results from
      this preliminary investigation suggest that CD34-positive stromal cells may
      disappear from the stroma of IMC as well as IDC.

PMID- 15735856
TI  - Myoepithelial cell markers in salivary gland neoplasms.
AB  - We compared the immunoexpression of 5 myoepithelial cell (MEC) markers (alpha
      smooth-muscle actin, calponin, h-caldesmon, vimentin, and S-100-protein) using 16
      pleomorphic adenomas (PA), 15 adenoid cystic carcinomas (ACC), and 3 epithelial
      myoepithelial carcinomas (EMC) of salivary glands. The alpha-smooth-muscle actin
      was useful for identification of MECs, especially in cribriform and tubular ACC,
      followed by EMC. Calponin was similar to alpha-smooth-muscle actin, except for
      polygonal and plasmacytoid cells of PA and for solid ACC, which showed alpha
      smooth-muscle actin negative and calponin positive. H-caldesmon was negative.
      Vimentin immunostained all MEC types, and was negative in luminal cells. S-100
      protein was expressed both in the nuclei and cytoplasm of MECs and luminal cells,
      especially in PA. The best way to identify MEC is using alpha-smooth-muscle actin
      or calponin, plus vimentin, since in tumors MECs are hardly ever fully
      differentiated.

PMID- 15735857
TI  - Correlation of periacinar retraction clefting in needle core biopsies and
      corresponding prostatectomy specimens of patients with prostatic adenocarcinoma.
AB  - One of the underemphasized supportive criteria for the diagnosis of prostatic
      cancer is the presence of retraction clefting around neoplastic glands. We
      analyzed a series of 152 prostatic cancer cases to determine the frequency,
      extent, and correlation of periacinar retraction clefting between needle core
      biopsies (NCB) and corresponding matched radical prostatectomy (RP) specimens.
      Clefting was significantly more frequent in neoplastic compared to nonneoplastic
      acini in NBC and RP (p<0.05). There was no significant difference in the
      frequency of retraction clefting in neoplastic acini between NCB and
      corresponding RP (p>0.05). We have also found a concordance in matched RP and NCB
      (Kappa=0.582). We conclude that periacinar retraction clefting appears more
      frequently in neoplastic acini and could serve as a reliable criterion in the
      diagnosis of prostatic adenocarcinoma.

PMID- 15735858
TI  - Follicular colonization of nodal marginal-zone B-cell lymphoma resembling
      follicular lymphoma: report of 6 cases.
AB  - The formation of neoplastic B-cell follicles is accepted as a diagnostic
      criterion of follicular lymphoma. However, extranodal marginal-zone B-cell
      lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes
      contain numerous lymphoid follicles and may even have a predominantly follicular
      growth pattern. However, morphologic, immunohistochemical, and genotypic findings
      suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles
      formed as the result of colonization of previously reactive follicles by tumor
      cells (centrocyte-like cells). We present here 6 cases of nodal MZBL
      demonstrating a follicular growth pattern. Immunohistochemical study demonstrated
      that the tumor cells were CD10-, CD20+, CD79a+,CD138-, Bcl-2+, Bcl-6- and IRF4+.
      Residual nonneoplastic follicular center cells were CD10+, CD20+, CD79a+, Bcl-2-,
      and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic
      cell pattern characteristic of follicular colonization in extranodal MZBL of MALT
      type. Taken in conjunction with the morphologic findings, nodal MZBL may also
      show a follicular growth pattern similar to extranodal MZBL of MALT type. The
      marginal-zone nature is most recognizable on immunohistochemistry, although the
      histologic appearance alone may cause some diagnostic problems. It is important
      for pathologists to consider this type of lesion in diagnostic practice.

PMID- 15735859
TI  - Adenofibromatous pattern in a solitary fibrous tumor of the lung.

PMID- 15735860
TI  - Primary alveolar soft part sarcoma (ASPS) of the breast: report of a deceptive
      case with xanthomatous features confirmed by TFE3 immunohistochemistry and
      electron microscopy.
AB  - Alveolar soft part sarcoma (ASPS) is a rare neoplasm that most commonly presents
      in the lower extremities. Although ASPS has distinctive histologic features, it
      may cause diagnostic problems when it arises in unusual locations. To our
      knowledge, only 1 case of ASPS arising within the breast has previously been
      reported. Here, we report a second case of primary mammary ASPS. The patient was
      a 44-year-old woman who presented with a breast mass. Needle biopsy was
      performed, yielding a polygonal cell lesion with abundant, predominantly
      xanthomatous cytoplasm. The cells labeled strongly for the histiocytic marker
      CD68, suggesting a benign macrophage-rich lesion. However, the unusual nature of
      the lesion as well as the prominence of nucleoli prompted suggestion for an
      excision. The excision more clearly revealed the lesion's alveolar architecture
      and demonstrated cells with more eosinophilic cytoplasm, along with the
      xanthomatous cells. The diagnosis of ASPS was confirmed by electron microscopy,
      which revealed characteristic membrane-bound rhomboidal crystals, as well as by
      nuclear labeling for TFE3 protein by immunohistochemistry. With this report, we
      confirm the utility of a novel immunohistochmical technique for the
      identification of an ASPS presenting in an unusual locale.

PMID- 15735861
TI  - Dual CD117 expression in gastrointestinal stromal tumor (GIST) and paraganglioma
      of Carney triad: a case report.
AB  - Carney triad is a rare syndrome, with only 20 complete cases reported. We report
      a 36-year-old white woman with complete Carney triad, including metastatic
      gastric stromal tumor (GIST), pulmonary chondroma, and nonfunctioning extra
      adrenal paraganglioma. Immunohistochemistry was positive for CD34 and CD117 (c
      kit) in the GIST, and positive for chromogranin and CD117 in the paraganglioma.
      Ultrastructural studies demonstrated skeinoid fibers in the GIST. To our
      knowledge, this is the 21st complete Carney triad case reported and the first
      report of dual expression CD117 in both GIST and paraganglioma, a finding with
      intriguing pathogenetic implications related to the organization of the autonomic
      nervous system.

PMID- 15735862
TI  - Cytokeratin-positive meningeal peripheral PNET/Ewing's sarcoma of the cervical
      spinal cord: diagnostic value of genetic analysis.
AB  - Peripheral primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES) of the
      central nervous system is extremely rare and should be differentiated from
      central PNET and other small blue round cell tumors. We describe a case of a
      meningeal peripheral PNET/ES of the spinal cord in an 11-year-old boy.
      Immunohistochemically, the small blue round cell tumor showed expression of
      epithelial markers and of CD99, thus posing an important differential diagnostic
      problem with a poorly differentiated synovial sarcoma. Fluorescence in situ
      hybridization revealed rearrangement of the EWS gene, as seen in peripheral
      PNET/ES. Peripheral PNET/ES does occur in the central nervous system, but its
      diagnosis can be extremely difficult on morphologic and immunohistochemical
      grounds alone. Genetic analysis plays a key role in its distinction from other
      small blue round cell tumors.

PMID- 15735863
TI  - Primary intranodal cellular angiolipoma.
AB  - Angiolipoma is a distinct, benign soft tissue tumor that most commonly occurs in
      young males as multiple small, subcutaneous, tender to painful nodules with
      predilection for the forearms. We report a case of angiolipoma that developed
      within a lymph node. The patient was a 67-year-old man who underwent radical
      retropubic prostatectomy with diagnostic pelvic lymphadenectomy because of
      adenocarcinoma of the prostate. The prostate and 3 lymph nodes located in the
      obturator fossa were removed. On gross examination, the cut surface of 1 of the
      lymph nodes revealed an 8 x 5 mm, ovoid, sharply demarcated, nonencapsulated,
      gray lesion being suspicious for adenocarcinoma metastasis. Microscopically, the
      major portion of the lymph node was replaced by mature metaplastic adipose
      tissue. The angiolipoma was seen as a well-demarcated, nonencapsulated lesion
      composed of numerous small blood vessels lined by monomorphous flattened or
      spindled endothelial cells. Many vascular lumina were filled with fibrin thrombi.
      There were scanty mature adipocytes. Focally, areas with increased cellularity
      and a suggestion of solid growth of the endothelial cells were seen. Lymph nodes
      are known to be a rare primary site of various tumors usually occurring in other
      organs. The knowledge of these tumors is important in order not to interpret them
      as metastatic lesions. The most recognized examples are pigmented nevi,
      palisading myofibroblastoma, various benign epithelial inclusions, serous cystic
      tumors of borderline malignancy, and hyperplastic mesothelial inclusions. As we
      present in this report, angiolipoma is another neoplasm whose primary occurrence
      in the lymph node should not be misinterpreted as a metastatic tumor or malignant
      vascular tumor.

PMID- 15735864
TI  - Splenic hamartoma: immunohistochemical and ultrastructural profile of two cases.
AB  - Splenic hamartoma (SH) is a rare, benign lesion. We present 2 cases, both in
      females (2 and 30 years, respectively) with multiple urinary tract infections,
      and left upper quadrant abdominal pain. Immunohistochemical staining with factor
      VIII displayed intense diffuse staining in the SH with corresponding weak
      staining in the adjacent spleen. CD31 showed a reverse pattern from that of
      factor VIII. CD34 staining pattern was identical in both the spleen and the SH.
      Ultrastructurally, the SH showed endothelial cells with relatively empty
      cytoplasm, scattered Weibel Palade bodies, and lining by basement membrane
      surrounded by fibrous long-spacing collagen. Our study highlights the unique
      immunohistochemical profile of SH. The ultrastructural features are interesting,
      although their diagnostic significance remains to be confirmed in future studies.

PMID- 15735865
TI  - Malignant ectomesenchymoma in the wrist of a child: case report and review of the
      literature.
AB  - Malignant ectomesenchymomas, rare and potentially aggressive tumors, occur in
      children and exhibit mesenchymal and neuroectodermal components. This report
      describes the first patient diagnosed with a malignant ectomesenchymoma of the
      hand. The patient was a 17-month-old male who developed a hypothenar mass on his
      left hand that was surgically excised. Microscopic evaluation revealed
      ganglioneuroblastic, rhabdomyosarcomatous, and chondrosarcomatous elements.
      Following excisional biopsy he was treated with cyclophosphamide, doxorubicin,
      vincristine, ifosfamide, and etoposide. After 3 courses of chemotherapy the
      patient had a wide reexcision with no residual tumor. The patient is 4 years from
      diagnosis, without evidence of disease.

PMID- 15735866
TI  - Low-grade myxofibrosarcoma of the vulva in a 15-year-old adolescent: a case
      report.

PMID- 15735867
TI  - Core biopsy and fine-needle aspiration: fit modus in rebus.

PMID- 15735869
TI  - Idiopathic plasmacytic lymphadenopathy with polyclonal gammopathy in a patient of
      Western origin.

PMID- 15735871
TI  - Challenges and recent developments in hearing aids. Part II. Feedback and
      occlusion effect reduction strategies, laser shell manufacturing processes, and
      other signal processing technologies.
AB  - This is the second part of a review on the challenges and recent developments in
      hearing aids. Feedback and the occlusion effect pose great challenges in hearing
      aid design and usage. Yet, conventional solutions to feedback and the occlusion
      effect often create a dilemma: the solution to one often leads to the other. This
      review discusses the advanced signal processing strategies to reduce feedback and
      some new approaches to reduce the occlusion effect. Specifically, the causes of
      three types of feedback (acoustic, mechanical, and electromagnetic) are
      discussed. The strategies currently used to reduce acoustic feedback (i.e.,
      adaptive feedback reduction algorithms using adaptive gain reduction, notch
      filtering, and phase cancellation strategies) and the design of new receivers
      that are built to reduce mechanical and electromagnetic feedback are explained.
      In addition, various new strategies (i.e., redesigned sound delivery devices and
      receiver-in-the-ear-canal hearing aid configuration) to reduce the occlusion
      effect are reviewed. Many manufacturers have recently adopted laser shell
      manufacturing technologies to overcome problems associated with manufacturing
      custom hearing aid shells. The mechanisms of selected laser sintering and stereo
      lithographic apparatus and the properties of custom shells produced by these two
      processes are reviewed. Further, various new developments in hearing aid
      transducers, telecoils, channel-free amplification, open-platform programming
      options, rechargeable hearing aids, ear-level frequency modulated (FM) receivers,
      wireless Bluetooth FM systems, and wireless programming options are briefly
      explained and discussed. Finally, the applications of advanced hearing aid
      technologies to enhance other devices such as cochlear implants, hearing
      protectors, and cellular phones are discussed.

PMID- 15735872
TI  - Childhood injuries: prevention is always better than cure.

PMID- 15735873
TI  - Rene Laennec (1781-1826): inventor of the stethoscope.

PMID- 15735874
TI  - How to read a paper: critical appraisal of studies for application in healthcare.
AB  - Finding and using research results to support your professional decisions must be
      a systematic process, based on the principles of evidence-based medicine and
      healthcare. This article takes you through a critical appraisal exercise using a
      recent article from the British Medical Journal as an example. It describes how
      you decide whether to read and use an article that may be relevant to your
      decision. The reading is guided by a series of questions. First you evaluate the
      validity of the article: is the study conducted and reported so that you may
      trust the results? The second set of questions discusses the outcomes, the effect
      of the intervention and describes the use of confidence intervals for this. The
      possibility of using the research results in the reader's setting and patient
      population is then evaluated.

PMID- 15735875
TI  - Childhood injuries in Singapore: a community nationwide study.
AB  - INTRODUCTION: Childhood injuries are the leading cause of death for children
      between 5 to 14 years of age in Singapore. However, there is no information or
      data on childhood injuries in the community in Singapore. There was a need to
      conduct a nationwide study on childhood injuries in Singapore in order to
      estimate the prevalence rate, types of injuries, and to identify the hazards in
      the homes of the children. METHODS: A cross-sectional nationwide study with a two
      stage stratified random sampling was conducted to obtain a representative sample
      of the Singapore population. Families that had children younger than 15 years of
      age were selected for the study. Parents and caregivers were interviewed at their
      homes. RESULTS: There were 2322 children in the study, of which 452 had one or
      more injuries in the past one year, giving an overall prevalence rate of 19.5
      percent. Of the children who had injuries, the home was the commonest place where
      injuries occurred (45 percent) and falls were the leading cause of injuries (77
      percent). There were many hazards identified in the homes studied and it was
      found that the more hazards present in the homes, the more likely it is for the
      child to get injuries. CONCLUSION: There is a need for educational and
      interventional programmes to help Singaporeans understand the need to make the
      home environment safe for children and to prevent home injuries.

PMID- 15735877
TI  - Type 2 diabetes mellitus with hypertension at primary healthcare level in
      Malaysia: are they managed according to guidelines?
AB  - INTRODUCTION: A study was conducted at primary healthcare level in the Melaka
      Tengah district of Malaysia to determine whether hypertension in patients with
      type 2 diabetes mellitus were managed according to guidelines. METHODS: A cross
      sectional study involving 517 patients with diabetes mellitus from August to
      October 2003 was performed. RESULTS: All the subjects had type 2 diabetes
      mellitus. 350 (67.7 percent) patients had hypertension and about 25.7 percent of
      them were associated with microalbuminuria. The Malay ethnic group form the
      majority (54.6 percent), followed by Chinese (37.7 percent) and Indian (7.4
      percent). Only 11 (3.1 percent) patients with type 2 diabetes mellitus and
      hypertension achieved the target blood pressure of less than 130/80 mmHg. For
      those who had not achieved the target goal, 39.5 percent of them were not on any
      antihypertensive drugs. 38.6 percent were on monotherapy and only 21.8 percent
      were on two or more antihypertensive drugs. Metoprolol was the most commonly used
      antihypertensive drug (22.4 percent), followed by Nifedipine (16.2 percent) and
      Prazosin (13.5 percent). Only 18.3 percent of patients with type 2 diabetes
      mellitus and hypertension were prescribed with angiotensin converting enzyme
      (ACE) inhibitors and 0.3 percent with angiotensin receptor blockers. For patients
      with type 2 diabetes mellitus, hypertension and microalbuminuria, only 14.1
      percent of them were prescribed with ACE inhibitors. CONCLUSION: A significant
      proportion of patients with type 2 diabetes mellitus had associated hypertension
      but they were not managed optimally according to guidelines. More intensive
      management of hypertension among patients with diabetes is essential to reduce
      the morbidity and mortality at primary healthcare level.

PMID- 15735876
TI  - Knowledge, attitude and practices of childhood injuries and their prevention by
      primary caregivers in Singapore.
AB  - INTRODUCTION: Childhood injuries are the leading cause of death for children
      between 5 to 14 years of age in Singapore. There have been no studies done on
      primary caregivers' knowledge, attitude and practices on childhood injuries and
      its prevention in Singapore. Thus there is a need to conduct this type of study
      in order to develop appropriate educational programmes. METHODS: A cross
      sectional nationwide study with a two-stage stratified random sampling was
      conducted to obtain a representative sample of the Singapore population. Families
      that had children younger than 15 years of age were selected for the study.
      Parents and caregivers were interviewed at their homes. RESULTS: The primary
      caregivers had good knowledge of road safety but poor knowledge on home safety
      and first aid. The higher the education of the mother, the more likely it is that
      she would possess the correct knowledge and practice on childhood injuries and
      its prevention. The media plays an important role on information on child safety
      of the caregivers. Only 38 percent said they obtained information from doctors
      and other health personnel. CONCLUSION: There is a need to educate parents and
      caregivers on home safety and first aid. Doctors and nurses should take a more
      active role in giving advice on child safety.

PMID- 15735878
TI  - In-vitro fertilisation in women aged 40 years and above.
AB  - INTRODUCTION: To compare the results of in-vitro fertilisation (IVF) in women
      aged less than 40 years with those aged 40 years and above with baseline follicle
      stimulating hormone (FSH) levels less than 15iu and using their own oocytes.
      METHODS: A total of 2179 fresh IVF cycles were started in KK Women's and
      Children's Hospital IVF Centre from 1997 to 2002, of which 247 cycles were done
      in women 40 to 45 years with FSH levels less than 15iu. The remaining 1932 cycles
      were performed in another group of women aged less than 40 years old. All couples
      were treated using our hospital's IVF protocol, and the same clinical and
      embryological team was involved in all treatments. The medical records of patient
      outcomes were retrospectively reviewed. The main outcomes measured were clinical
      pregnancy, miscarriage and delivery rates. RESULTS: The total number of fresh
      cycles performed in women over 40 years was 247 cycles. Of these, 186 (75.3
      percent) cycles reached oocyte collection, and 179 (72.5 percent) cycles reached
      embryo transfer. The total number of pregnancies was 22 (12.3 percent). The
      number of cancelled cycles was 61 (24.7 percent). Women less than 40 years of age
      demonstrated higher rates in cycles reaching oocyte collection (89.2 percent),
      embryo transfer (84.6 percent), pregnancy rates (32.9 percent) and live-birth
      rates (24.0 percent). They also reported a lower miscarriage (36.1 percent) and
      cancellation rate (10.9 percent) as compared to the group of older women.
      CONCLUSION: As older women seek IVF treatment, it is necessary for them to
      understand that chances of pregnancy decrease with increasing age. Our results
      show that as women exceed 40 years old, pregnancy and live-birth rates fall with
      concurrent rising miscarriage and cycle cancellation rates.

PMID- 15735879
TI  - Meniscal cyst causing periarticular tibial erosion.
AB  - Meniscal cysts causing bone erosions are rare. The majority of meniscal cysts are
      associated with tears of the menisci and magnetic resonance (MR) imaging
      appearances are usually diagnostic. The MR images of a 34-year-old man showed a
      well-defined cystic mass that communicated with a horizontal cleavage tear of the
      posterior horn of the lateral meniscus and caused pressure erosion of the lateral
      tibial condyle. We believe this to be the first locally reported case of tibial
      erosion related to a meniscal cyst. This entity should be included in the
      differential diagnosis for a well-defined periarticular erosion.

PMID- 15735880
TI  - Sclerosing haemangioma mimicking hepatocellular carcinoma.
AB  - Sclerosing haemangioma is a rare variant of hepatic haemangioma. The radiological
      features on computed tomography and magnetic resonance imaging may not be typical
      for haemangioma and can be confused with hepatocellular carcinoma. We report
      sclerosing haemangioma occurring in a 65-year-old woman where the radiological
      features raise the possibility of hepatocellular carcinoma.

PMID- 15735881
TI  - Electrocardiographical case. Elderly woman with sudden onset of post-operative
      dyspnoea.
AB  - A 70-year-old Chinese woman developed breathlessness, tachycardia and hypotension
      on the fourth day after total hip replacement. 12-lead electrocardiogram (ECG)
      showed sinus tachycardia with ST depression in I, II, V5 and V6. The ECG changes
      of sinus tachycardia along with a typical history is suggestive of pulmonary
      embolism. Diagnosis, treatment and the use of IVC filter for pulmonary embolism
      are discussed.

PMID- 15735883
TI  - Fibrinolysis of loculated pleural effusion in malignant mesothelioma.

PMID- 15735886
TI  - [Home cardiorespiratory sleep study in children. Will it be feasible?].
AB  - Childhood obstructive sleep apnea syndrome is a common condition and can result
      in serious complications. The nocturnal polysomnography remains the gold standard
      in the diagnosis of this pathology. Given the scarcity of sleep laboratories,
      namely with paediatric profile, screening techniques have been commonly used. It
      was our aim to study the yield of the home cardiorespiratory sleep studies
      carried out in children. Since January of 1999 until June of 2003, 33 home
      cardiorespiratory sleep studies were performed in children. We studied 31
      children (21 male) with a median age of 10.6+/-3.4 years. Five children had
      craniofacial malformations, 2 neuromuscular diseases and 10 were obese. The
      signals of nasal flow and saturation were good/acceptable in 67.7% and 96.8% of
      the cases, respectively. In 2 cases the register was null. Average of apnea
      hypopnea index was of 10.7+/-12.3/hour, average saturation of 95.6%+/-3.0 %,
      minimum saturation of 82.2 %+/-9.2% and dessaturation index of 12.5+/-10.7/hour.
      Childhood obstructive sleep apnea syndrome was confirmed/suggested in 30
      children. The apnea-hypopnea index and the dessaturation index were significantly
      higher in the group of children with craniofacial malformations and neuromuscular
      disorders comparatively to children with obesity (26.3 versus 10.5 and 21.5
      versus 11.3, respectively) but without statistical significance. In our
      experience, home cardiorespiratory sleep studies is a diagnostic method easily
      used in children. This method gives more information comparatively to other
      screening techniques so that it can evaluate with more accuracy the existence of
      sleep disordered breathing and may be a possible alternative to polysomnography.

PMID- 15735887
TI  - [Lung cancer and cutaneous metastasis].
AB  - The authors did a review of patients with lung neoplasms and cutaneous
      metatization diagnosed in the period from 1999 to 2004 and followed in the
      Pneumologic Oncologic department of the Hospital Sousa Martins (H SM). We have
      analysed the following variables: sex, race, hystologic diagnosis, clinical
      stage, therapeutics, impact of the appearance of cutaneous metastization and
      survival time. Five of the 114 patients with lung neoplasms (4.3%), presented
      with cutaneous metastization, two males and three females with an average age of
      69 years. In one of the patients the cutaneous lesions were synchronic, and in
      the others were metachronic. The most prevalent histologic type was the
      adenocarcinoma. The average survival time after the cutaneous metastization was
      3.8 months. The results are compared with others present in the world literature.

PMID- 15735888
TI  - [High resolution computed tomography findings in parainfluenza virus pneumonia
      after bone marrow transplantation: case report].
AB  - Nineteen year-old female patient, who underwent bone marrow transplantation
      because of chronic myelogenous leukemia, presented with dry cough and coriza
      sixty-seven days after the procedure. The chest radiograph was normal. The high
      resolution computed tomography showed a subsegmental air-space consolidation at
      the periphery of the left inferior lobe and areas of low attenuation at the
      superior and middle lung zones. The bronchoalveolar lavage demonstrated positive
      direct fluorescence antibody testing against parainfluenza virus. Treatment with
      aerolizated ribavirin was instituted during 10 days and the patient showed
      clinical-radiological improvement.

PMID- 15735889
TI  - [Broncho-mediastinal fistula -- a rare manifestation of a tumor].
AB  - Broncho-mediastinal fistulaes are a very rare condition, existing only a report
      of a case related with primary lung cancer. The authors present a clinical case
      of a white 58-year-old man, with previous history of cigarette smoking and
      diabetes, with fever, productive cough and progressive dyspnea, with radiological
      evidence of right inferior lobar pneumonia. We noticed a radiological
      deterioration, despite the high spectrum antibiotic therapy, so he was submitted
      to thoracic computerized tomography and broncofibroscopy, which revealed
      extensive infiltration of the principal and intermediary bronchioles with a
      broncho-mediastinal-esophagic fistula. The histological exam revealed a
      pavimentam cellular carcinoma.

PMID- 15735890
TI  - [Amyotrophic Lateral Sclerosis revealed by acute respiratory failure: two case
      studies].
AB  - Amyotrophic Lateral Sclerosis (ALS) is a fast progressing neuromuscular disease
      that affects all but the extrinsic muscles of the eye and sphincters. The main
      cause of morbidity and mortality are the respiratory complications that usually
      start in a late stage of the diseases natural history. In a small number of cases
      acute respiratory failure is the initial manifestation of the disease. The
      authors present 2 case studies admitted to a pulmonary department, without
      previously known neuromuscular disease, with the diagnosis of acute respiratory
      failure of unknown etiology and that were later shown to be cases of ALS.
      Analysis of the cases presented here, and those already published in the
      literature, suggests that the occurrence of acute respiratory failure in patients
      without a previous history of pulmonary and/or heart disease, especially in the
      5th and 6th decade of life, should alert to ALS as a possible diagnosis.

PMID- 15735891
TI  - Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with
      type 2 diabetes in the Danish population.
AB  - AIMS/HYPOTHESIS: The hepatocyte nuclear factor (HNF)-4alpha is an orphan nuclear
      receptor, which plays crucial roles in regulating hepatic gluconeogenesis and
      insulin secretion. The gene encoding HNF-4alpha (HNF4A) is located on chromosome
      20q12-q13 in a region that in several studies has shown linkage with type 2
      diabetes. Recently, two independent studies identified single nucleotide
      polymorphisms (SNPs) in a 90-kb region spanning HNF4A, which showed strong
      association with type 2 diabetes in the Finnish and Ashkenazi Jewish populations.
      In an attempt to replicate and extend these findings, we selected four SNPs in
      the same HNF4A region, which in the Finnish and Ashkenazi Jewish populations were
      associated with type 2 diabetes, and examined their relationships with type 2
      diabetes and prediabetic phenotypes in the Danish Caucasian population. METHODS:
      The rs1884614, rs2425637, rs1885088 and rs3818247 were analysed in case-control
      studies of 1387, 1429, 1417 and 1371 type 2 diabetic patients and 4766, 4727,
      4665 and 4748 glucose-tolerant subjects respectively. Genotype-quantitative trait
      analyses comprised 4430, 4394, 4336 and 4413 middle-aged glucose-tolerant
      subjects from the population-based Inter99 cohort for the rs1884614, rs2425637,
      rs1885088 and rs3818247 respectively. RESULTS: The risk allele of the rs1884614,
      which is located 4 kb upstream of the HNF4A P2 promoter, was associated with type
      2 diabetes (odds ratio [OR]=1.14, p=0.02) and with a subtle increase in post-OGTT
      plasma glucose levels in glucose-tolerant subjects (additive model, p=0.05).
      CONCLUSIONS/INTERPRETATION: Consistent with results from studies of Finnish and
      Ashkenazi Jewish subjects, variation near the P2 region of HNF4A is associated
      with type 2 diabetes in the Danish population.

PMID- 15735892
TI  - Effect of common polymorphisms in the HNF4alpha promoter on susceptibility to
      type 2 diabetes in the French Caucasian population.
AB  - AIMS/HYPOTHESIS: The gene encoding HNF-4alpha, an orphan nuclear receptor playing
      critical roles in embryogenesis and metabolism by regulating gene expression in
      pancreatic beta cells, liver, and other tissues, is localised to chromosome
      20q13, where linkage to type 2 diabetes has been shown in multiple studies. As
      two reports have independently demonstrated a convincing association with
      variants adjacent to the HNF-4alpha P2 promoter in Finnish and Ashkenazi Jewish
      populations, we evaluated their contribution to diabetes risk in the French
      Caucasian population. METHODS: Genotypes for four haplotype tag SNPs were
      analysed for association with diabetes in a case-control study of 744 unrelated
      type 2 diabetic patients and 686 normoglycaemic subjects, and for linkage in 148
      diabetic families in whom significant linkage to the HNF4alpha region had been
      shown. RESULTS: The association seen in the Finnish and Ashkenazi studies for
      SNPs rs2144908 and rs1884614 located within a haplotype block encompassing the
      beta cell promoter P2 of HNF-4alpha was not replicated in our study; in French
      Caucasians the minor allele prevalence was increased in control subjects [odds
      ratio (OR) 0.80, uncorrected p=0.022 for rs2144908; OR 0.82 uncorrected p=0.058
      for rs1884614]. Furthermore, none of the SNPs tested in the French familial
      sample was associated with diabetes, nor do they appear to contribute to the
      linkage. CONCLUSIONS/INTERPRETATION: None of the previously associated SNPs
      confer an increased risk for diabetes in French Caucasians. A large meta-analysis
      of association studies will determine whether there is a consistent association
      between particular SNPs upstream of HNF-4alpha and type 2 diabetes in several
      ethnic groups.

PMID- 15735893
TI  - [Antimicrobial peptides. A perspective for the treatment of chronic wounds?].
AB  - Human antimicrobial peptides play a substantial role in the immune response to
      various dermatological diseases, such as acne, atopic dermatitis and psoriasis
      vulgaris, and even mucosal HIV-protection is mediated inter alia by antimicrobial
      peptides. In wound healing, the antimicrobial and immune-modulating properties
      of, in particular, human defensins and cathelicidins can affect important
      controlling factors. For example, the interaction between different antimicrobial
      peptides and growth factors supports neoangiogenesis. Although further clinical
      investigations are necessary to identify the exact effects of antimicrobial
      peptides in chronic wounds, such peptides could be a promising therapeutic option
      in the near future for the treatment of patients with chronic wounds by promoting
      endogen expression or exogenous supplementation.

PMID- 15735894
TI  - Suprapubically assisted operative cystoscopy in the management of intravesical
      TVT synthetic mesh segments.
AB  - The tension-free vaginal tape (TVT) sling has become one of the most common
      procedures performed for the treatment of female stress incontinence.
      Perforations of the bladder during the TVT placement are relatively common, but
      are usually noted on cystoscopy and corrected at the time of the procedure.
      Undetected perforation may result in several complications including recurrent
      urinary tract infections, bladder stone formation, and pelvic pain. A novel
      technique is described using operative cystoscopy with suprapubic assistance,
      which provides an effective means for resection of intravesical mesh. Unlike
      traditional approaches via laparotomy, this minimally invasive procedure may
      allow for successful mesh removal while avoiding the morbidity of an open
      procedure.

PMID- 15735896
TI  - A review of osteoinductive testing methods and sterilization processes for
      demineralized bone.
AB  - Allogeneic demineralized bone has been used extensively as a clinical graft
      material because it has osteoinductive and osteoconductive properties. Concerns
      over processing and terminal sterilization procedures that may reduce performance
      have led clinicians to call for assurances of product potency. There is extensive
      experience on effects of demineralized bone in animal and cell culture models
      with the possibility for future evidence-based standards for release of products.
      Evaluation of the current state of knowledge leads to the fact that we cannot
      conclude that performance of different lots of demineralized bone allografts in
      in vivo or in vitro test systems can be used as a measure of clinical
      performance. It may be possible to adopt an osteoinductivity standard for release
      to-market, but it should be followed by clinical monitoring and further research.

PMID- 15735897
TI  - Extractable bone morphogenetic protein and correlation with induced new bone
      formation in an in vivo assay in the athymic mouse model.
AB  - A correlation between extractable bone morphogenetic proteins (BMPs) in
      demineralized bone matrix (DBM) and osteoinduction has been suggested.
      Extractable BMP-4 and osteoinductivity of DBM from 40 donors were assessed using
      enzyme-linked immunosorbent assay (ELISA) and in vivo athymic mouse assay,
      respectively. Extractable BMP-4 level averaged 3.7 +/- 0.21 ng/g of DBM and
      correlated with osteoinductivity of the DBM in an in vivo assessment of induced
      newbone formation.

PMID- 15735898
TI  - Detection of living cells in non-processed but deep-frozen bone allografts.
AB  - Impacted morselized donor bone is successfully used to treat bone loss in
      revision total hip arthroplasties. It is generally thought, but not proven, that
      the processing and storage at -80 degrees C of the donor bone kills all cells.
      Because of the risk of contamination and to increase our understanding about the
      process of new bone formation after revision total hip arthroplasty, the aim of
      this study was to investigate whether the donor bone does contain vital cells.
      Samples from 11 femoral heads were obtained according to the American and
      European standards of bone banking, and tested for their capacity to give rise to
      proliferating cells, using tissue culture methods. All bone samples were stored
      at - 80 degrees C for a minimum of 6 months. Bone sample cores were morselized
      and cultured for 6 weeks. Inverted phase contrast microscopy was used to evaluate
      cell growth. DNA marker analysis was used to confirm cellular identity. All bank
      bone samples gave rise to cell growth. The cell cultures showed osteoblastic
      characteristics in that they expressed high levels of alkaline phosphatase
      activity. DNA marker analysis showed identical alleles for cultured cells from
      frozen bone and freshly obtained buccal cells from the same donor, indicating
      that the cells growing from the banked bone were indeed originating from the
      donor tissue. It was therefore concluded that -80 degrees C freezing of bone
      tissue does not routinely kill cells within the tissue.

PMID- 15735899
TI  - Demineralized bone promotes chondrocyte or osteoblast differentiation of human
      marrow stromal cells cultured in collagen sponges.
AB  - Demineralized bone implants have been used for many types of craniomaxillofacial,
      orthopedic, periodontal, and hand reconstruction procedures. In previous studies,
      we showed that demineralized bone powder (DBP) induces chondrogenesis of human
      dermal fibroblasts in a DBP/collagen sponge system that optimized interactions
      between particles of DBP and target cells in cell culture. In this study, we test
      the hypothesis that DBP promotes chondrogenesis or osteogenesis of human marrow
      stromal cells (hMSCs) in 3-D collagen sponge culture, depending upon the culture
      conditions. We first confirmed that hMSCs have chondrogenic potential when
      treated with TGF-beta, either in 2-D monolayer cultures or in 3-D porous collagen
      sponges. Second, we found that DBP markedly enhanced chondrogenesis in hMSCs in 3
      D sponges, as assessed by metachromasia and expression of chondrocyte-specific
      genes AGGRECAN, COL II, and COL X. Human dermal fibroblasts (hDFs) were used to
      define mechanisms of chondroinduction because unlike hMSCs they have no inherent
      chondrogenic potential. In situ hybridization revealed that hDFs vicinal to DBPs
      express chondrocyte-specific genes AGGRECAN or COL II. Macroarray analysis showed
      that DBP activates TGF-beta/BMP signaling pathway genes in hDFs. Finally, DBP
      induced hMSCs to express the osteoblast phenotype when cultured with osteogenic
      supplements. These studies show how culture conditions can influence the
      differentiation pathway that human marrow stromal cells follow when stimulated by
      DBP. These results support the potential to engineer cartilage or bone in vitro
      by using human bone marrow stromal cells and DBP/collagen scaffolds.

PMID- 15735900
TI  - Phenotypic analysis of bovine chondrocytes cultured in 3D collagen sponges:
      effect of serum substitutes.
AB  - Repair of damaged cartilage usually requires replacement tissue or substitute
      material. Tissue engineering is a promising means to produce replacement
      cartilage from autologous or allogeneic cell sources. Scaffolds provide a three
      dimensional (3D) structure that is essential for chondrocyte function and
      synthesis of cartilage-specific matrix proteins (collagen type II, aggrecan) and
      sulfated proteoglycans. In this study, we assessed porous, 3D collagen sponges
      for in vitro engineering of cartilage in both standard and serum-free culture
      conditions. Bovine articular chondrocytes (bACs) cultured in 3D sponges
      accumulated and maintained cartilage matrix over 4 weeks, as assessed by
      quantitative measures of matrix content, synthesis, and gene expression.
      Chondrogenesis by bACs cultured with Nutridoma as a serum replacement was
      equivalent or better than control cultures in serum. In contrast, chondrogenesis
      in insulin-transferrin-selenium (ITS(+3)) serum replacement cultures was poor,
      apparently due to decreased cell survival. These data indicate that porous 3D
      collagen sponges maintain chondrocyte viability, shape, and synthetic activity by
      providing an environment favorable for high-density chondrogenesis. With
      quantitative assays for cartilage-specific gene expression and biochemical
      measures of chondrogenesis in these studies, we conclude that the collagen
      sponges have potential as a scaffold for cartilage tissue engineering.

PMID- 15735902
TI  - Tissue banking in South Africa: a 19-year history.
AB  - The establishment of a Tissue Bank and the science of Tissue Banking in South
      Africa started in the 1960s and is still developing. This article describes the
      development and growth of Tissue Banking in South Africa. The current emphasis is
      to supply viable bone products that have been produced under the best possible
      quality controlled circumstances; with the collaboration between different Organ
      Donation Organisations. Through collaboration, a dramatic increase in the number
      of donors was noted over the years. Concurrently, there was a dramatic increase
      in the usage of different allograft products and now necessitates the development
      of new graft materials for expanding patient options. As an ongoing concern, the
      Tissue Bank in South Africa experienced an ever increase in costs to enhance
      quality/safety controls: increase in historical patient information,
      documentation and serological testing in a population struggling to control HIV.
      To date, the South African Tissue Bank has not experienced any untoward patient
      incidence since the 1960s and currently is getting over 500 donors per year.

PMID- 15735901
TI  - Osteogenic cell contact with biomaterials influences phenotype expression.
AB  - Relationship between (1) osteoblast adhesion and spreading, and (2) phenotype
      expression was investigated. Cellular adhesion and spreading were estimated after
      short time (24 h), whereas proliferation and other osteoblast functions--after 7
      days. Primary human osteogenic cells were seeded on the samples of titanium (T),
      surgical steel (S) and tissue culture polystyrene (PS), and incubated at 37
      degrees C. After 24 h a number of samples were stained with crystal violet and
      Hoechst; the average single cell area (spreading) and adhering cell number was
      measured on each sample. The remaining cultures were supplemented with
      dexamethasone (10 nM) and beta-glycerophosphate (5 mM), and incubation was
      continued for 7 days. The cells on each sample were counted and the following
      tests were performed: XTT mitochondrial activity assay, total protein content,
      alkaline phosphatase activity (ALP), Sirius Red test for collagen, osteocalcin
      and calcium concentration. After 24 h significantly greater cell spreading (p <
      0.05) and number (p < 0.05) were on T than on S. After 7 days significantly
      higher on T than on S were: ALP activity (p < 0.000001), collagen (p < 0.0015)
      and calcium concentration (p < 0.03). XTT results were bigger on S than on T. In
      control - XTT results were higher than on the metals; collagen and ALP were lower
      than on T, and calcium level was significantly lower than on T and S (p < 0.025).
      After 7 days there were no differences in cell number between T and S. Cell
      number (24 h) correlated with ALP activity (7 days) on steel (coefficient of
      correlation, CC = 0.866) and titanium (CC = 0.742). The spreading correlated on
      steel and on titanium with calcium concentration (CC = 0.645 on S, CC = 0.696 on
      T) and collagen level (CC = -0.638 on S, CC = -0.69 on T). CONCLUSIONS: Better
      conditions for osteoblast phenotype expression on T after 7 days of culture
      coincided with greater adhesion and spreading of cells after 24 h on T, as
      compared with S. The initial contact of cells with underlying surface may
      influence osteoblast functions and possibly, bone regeneration and implant
      osteointegration in vivo. Early cell spreading may be an indicator of further
      expression of osteoblast phenotype and may be important for application of
      osteogenic cells in reconstructive surgery.

PMID- 15735904
TI  - A method for the determination of the residual chloroform in defatted cancellous
      bone transplants.
AB  - The removal of fat from cancellous bone tissue promotes the clinical healing of
      the transplant and improves the penetration of chemical sterilisation media into
      the tissue. Treatment using chloroform/methanol (2:1, 2 h) is frequently used as
      a defatting procedure. Eight rinses with methanol followed by two rinses with
      aqua ad iniectabilia (20 min each, with ultrasonic effect) ensure depletion in
      the level of chloroform from defatted cancellous bone to a concentration below 25
      ppm (limit value). For the necessary routine quality checks on the production
      process, a gas chromatography method has been developed that determines the level
      of chloroform in cancellous bone, for which the detection limit is 0.003 ppm.

PMID- 15735908
TI  - PKB/Akt mediates radiosensitization by the signaling inhibitor LY294002 in human
      malignant gliomas.
AB  - The phosphoinositide 3-kinase (PI3-kinase) signaling pathway is frequently
      aberrantly activated in glioblastoma multiforme (GM) by mutation or loss of the
      3' phospholipid phosphatase PTEN. PTEN abnormalities result in inappropriate
      signaling to downstream molecules including protein kinase B (PKB/Akt), and
      mammalian target of rapamycin (mTOR). PI3-kinase activation increases resistance
      to radiation-induced cell death; conversely, PI3-kinase inhibition enhances the
      sensitivity of tumors to radiation. The effects of LY294002, a biochemical
      inhibitor of PI3-kinase, on the response to radiation were examined in the PTEN
      mutant glioma cell line U251 MG. Low doses of LY294002 sensitized U251 MG to
      clinically relevant doses of radiation. In contrast to LY294002, rapamycin, an
      inhibitor of mTOR, did not result in radiosensitization. We demonstrate that
      among multiple known targets of LY294002, PI3-kinase is the most likely molecule
      responsible for LY294002-induced radiosensitization. Furthermore, using a
      myristoylated PKB/Akt construct, we identified PKB/Akt as the downstream molecule
      that mediates the synergistic cytotoxicity between LY294002 and radiation. Thus
      PI3-kinase dysregulation may contribute to the notable radioresistance of GM
      tumors and inhibition of PKB/Akt offers an excellent target to enhance
      radiosensitivity.

PMID- 15735909
TI  - PAX6 suppresses growth of human glioblastoma cells.
AB  - PURPOSE: Glioblastomas (GBMs) are the most common primary malignant brain tumors.
      Majority of GBMs has loss of heterozygosity of chromosome 10. The PAX6 encodes a
      transcription factor that involves in development of the brain, where its
      expression persists. We have reported that the expression of PAX6 was
      significantly reduced in GBMs and that a low level of PAX6 expression is a
      harbinger of an unfavorable prognosis for patients with malignant astrocytic
      glioma. Interestingly, PAX6 expression was increased in suppressed somatic cell
      hybrids derived from introducing a normal human chromosome 10 into U251 GBM
      cells. Thus it is interesting to determine if repression of PAX6 expression is
      involved in anti-tumor suppression function in GBM. EXPERIMENTAL DESIGN: We
      overexpressed PAX6 in a GBM cell line U251HF via either stable transfection or
      infection with recombinant adenovirus, and examined cell growth in vitro and in
      vivo. RESULT: Although we did not observe changes in the cell doubling time for
      PAX6-stable transfectants, significantly fewer numbers of PAX6-positive colonies
      grew in soft agar. Transient overexpression of PAX6 via adenovirus, however,
      suppressed cell growth by increasing the number of cells in G1 and by decreasing
      the number of cells in S-phase, and later on caused a dramatic level of cell
      death. Repeated subcutaneous and intracranial implantation experiments in nude
      mice using PAX6-stable transfectants provided solid evidence that PAX6 suppressed
      tumor growth in vivo and significantly extended mouse survival. CONCLUSION: Our
      data demonstrate that PAX6exerts a tumor suppressor function that limits the
      growth of GBM cells.

PMID- 15735910
TI  - T cell response to Hu-D peptides in patients with anti-Hu syndrome.
AB  - The anti-Hu syndrome is the most common paraneoplastic neurologic syndrome but
      the exact mechanism of immune mediated neuronal injury remains unknown. Anti-Hu
      antibodies do not appear to play a pivotal role in the pathogenesis of the
      disease. To assess cell-mediated immunity, we selected 51 peptides from the Hu-D
      sequence and tested their ability to bind to six common HLA class I molecules.
      Stable complexes with purified HLA molecules were obtained with 19/51 (37%)
      selected peptides. Subsequently, the ability of the 19 HLA-binding peptides to
      stimulate T cells from 10 patients and 10 control subjects was evaluated by
      detecting IFN-gamma secretion. An anti-peptide T-cell response was observed in
      7/10 Hu-positive patients but also in 3/10 control subjects. Overall, a
      significant T-cell activation occurred in response to 74% (14 out of 19) of the
      selected peptides in the Hu-positive patients vs. 16% (3 out of 19) in the
      control group (p < 0.001). In addition, T cells of patients tested within 3
      months of the onset of anti-Hu syndrome responded to 82% (14 out of 17) of
      assessed Hu-D peptides vs. 37% (7 out of 19) in patients tested 1 year or more
      after developing the syndrome (p < 0.01). Thus, the present study suggests a role
      of cellular immunity during the course of anti-Hu syndrome.

PMID- 15735911
TI  - Cell proliferative activity estimated by histone H2B mRNA level correlates with
      cytogenetic damage induced by radiation in human glioblastoma cell lines.
AB  - We studied the relationship between proliferative activity and radiation-induced
      DNA damage in human malignant gliomas in vitro. Nine human glioblastoma
      established cell lines were gamma-irradiated (60Co) over a dose range of 0-10 Gy.
      H2B and H4 histone mRNA level was assessed with quantitative RT-PCR technique
      (TaqMan) and histone labeling index (HLI) with in situ hybridization to define
      proliferation rate, while cytochalasin-block micronucleus assay was performed to
      measure cytogenetic damage. Micronucleus frequency correlated with H2B mRNA level
      (Spearman's R up to 0.82 at 8 Gy), HLI, nuclear division index (NDI) and
      percentage of binucleated cells (%BNC). There was a high correlation between H2B
      mRNA level and NDI (R = 0.80) as well as %BNC and HLI (R = 0.72). Histone H2B and
      H4 mRNA level (not significant), HLI, NDI, and %BNC (significant) were higher in
      cell lines sensitive to DNA damage. Proliferative activity correlates with
      radiation-induced DNA damage in human glioma cell lines. Histone H2B mRNA level
      and HLI may be a useful molecular predictor of the tumour response to radiation
      treatment in gliomas of the same histological grade, however the risk of
      potentially more rapid tumour-cell repopulation must be considered. Presumed
      protective activity of histones against radiation-induced DNA damage was not
      confirmed at the transcript level.

PMID- 15735913
TI  - Cavernous hemangioma of the thalamus.

PMID- 15735912
TI  - Up-regulation of neuropoiesis generating glial progenitors that infiltrate rat
      intracranial glioma.
AB  - To investigate adult neural stem cell (NSC) biology in relation to glioma, the C6
      glioma cell line was tagged with green fluorescent protein (GFP) and inoculated
      into the brain of adult rats. The in vivo biological response of the brain to
      glioma was studied using immunohistochemical analysis of the subventricular zone
      (SVZ), peritumoral areas, and glioma. Nestin immunoreactive cells were found
      infiltrating glioma, but the distribution of abnormal immunoreactivity was
      restricted to the dorsal and medial border of the tumor relative to the
      ipsilateral ventricle. The SVZ was found to be hypertrophic, hypercellular, and
      up-regulated nestin expression. Furthermore, a dense contiguous population of
      nestin immunoreactive cells could be found streaming from ipsilateral dorsal tip
      of the SVZ, tracking along the ventral margin of the corpus callosum, and fanning
      out to encompass and infiltrate the proximal tumor border. Although most cells
      were either nestin or glial fibrillary acidic protein (GFAP) immunoreactive in
      the SVZ and along the ventral margin of the corpus callosum, the number of cells
      co-expressing both markers increased proportionally as the tumor was approached
      so that the predominant cell population along the proximal tumor border was GFAP
      immunoreactive. Finally, we demonstrated that a significant proportion of cells
      found in areas of abnormal immunoreactivity were proliferating, especially in
      peritumoral areas. In summary, there is an induction of neuropoietic activity in
      a rat intracranial glioma model that results in an infiltration and accumulation
      of abnormal nestin and GFAP expressing cells with proliferative potential along
      the dorsal and medial border of intracranial C6 glioma.

PMID- 15735914
TI  - Double-platinum chemotherapy combined with etoposide in metastatic brain tumor
      from small cell lung carcinoma.
AB  - The platinum-based chemotherapeutic agents, such as cisplatin (CDDP) and
      carboplatin (CBDCA), are effective for small cell lung carcinoma (SCLC). However,
      high dose treatment of these agents required for advanced-stage SCLC is often
      associated with severe toxicity. The authors used combination of lower doses of
      both cisplatin and carboplatin combined with etoposide (VP-16) to minimize side
      effects of these agents. This goal was accomplished by utilizing the facts that
      each agent has its own toxicity that can be controlled individually. Two patients
      (60- and 71-year old men) with multiple metastatic brain tumors from SCLC were
      treated by our chemotherapeutic regimen. After fourth chemotherapy, remarkable
      shrinking of brain masses was associated with significant decrease the size of
      original lung lesions in both cases. The two patients were discharged without any
      side effects of the treatment, and neurological deficits subsided in both cases.
      Each course provided the following schedules: carboplatin 200 mg/m2 x 1 day,
      cisplatin 25 mg/m2 x 2 days (intravenous administration), and etoposide 25 mg
      oral x 14 days. After second chemotherapy, the patient of Case 1 was irradiated
      to both brain and chest lesions, and only to brain in Case 2. The authors
      concluded from our two cases that the combination of these agents extremely
      effective to treat this malignancy with less toxicity. We named this double
      platinum chemotherapy as 'PEC', abbreviated from cisplatin, etoposide, and
      carboplatin. m

PMID- 15735915
TI  - Stroke as a first manifestation of ovarian cancer.
AB  - BACKGROUND: Gynaecologic neoplasms are reported to have the highest potential for
      developing of ischemic stroke. OBJECTIVES: The history of a female patient, in
      whom recurrent cerebral embolism was the first clinical sign of occult ovarian
      neoplasm is described and the casuistic literature to characterise this clinical
      phenomenon reviewed. RESULTS: Among a large spectrum of neoplasms complicating
      with ischemic stroke, ovarian carcinoma is one of the most frequently reported in
      the casuistic literature. The source of systemic microembolisation is endocardits
      of non-infectious origin; the characteristic diagnostic findings are
      thrombocytopenia, elevated D-dimers level, and a specific stroke pattern in
      magnetic resonance imaging. CONCLUSION: Meticulous diagnosis in female, otherwise
      'healthy' patients with ischemic stroke, to detect the underlying neoplastic
      disease is of paramount importance, as early surgical intervention on cancer
      promises successful therapy for both, cancer and thromboembolism.

PMID- 15735916
TI  - Combined chemotherapy and radiotherapy for intracranial germinomas in adult
      patients: a single-institution study.
AB  - We report on our experience in the treatment of intracranial germinomas (18 pure
      germinomas and two germinomas with syncytiotrophoblastic giant cells) according
      to a strategy of radiotherapy doses and fields reduction after a neoadjuvant
      chemotherapy (Cisplatin-vinblastine and bleomycin combination). Radiation therapy
      was delivered after the completion of the third and last course of chemotherapy.
      For the solitary germinoma the target volume was the gross tumour volume. In the
      five multifocal germinoma patients the whole ventricle volume was irradiated. For
      the single disseminated germinoma patient we treated the whole central nervous
      system. The cumulative doses were 30 Gy for the pure germinomas. For the STGCs, a
      cumulative dose of 35 Gy was used. The median follow-up was 55 months (range 12
      120). 18 patients were alive without recurrence of disease. In the two patients
      with STGCs the death took place 16 and 35 months after diagnosis.

PMID- 15735917
TI  - Gefitinib ('Iressa', ZD1839) is active against brain metastases in a 77 year old
      patient.
AB  - This report highlights the case of a symptomatic 77-year-old non-smoking female
      patient who was diagnosed with advanced non-small-cell lung cancer (NSCLC),
      metastatic to the liver and contralateral lung. After tumor progression in the
      liver and lung following polychemotherapy, multiple diffuse brain and cerebellar
      metastases were apparent. Oral treatment with the epidermal growth factor
      receptor tyrosine kinase inhibitor gefitinib ('Iressa') 250 mg/day resulted in
      progressive and durable symptom relief, and improvements in quality of life and
      performance status. Reductions in the size of the primary pulmonary tumor and
      brain, cerebellar, and liver metastases were observed. Furthermore, gefitinib was
      well tolerated with an absence of adverse events. These results provide evidence
      that oral gefitinib is active in patients with advanced NSCLC and central nervous
      system metastases.

PMID- 15735918
TI  - Assessing perfusion changes during whole brain irradiation for patients with
      cerebral metastases.
AB  - PURPOSE: To assess perfusion changes within brain and correlate these with
      clinical symptoms during whole brain radiotherapy (WBRT) for cerebral metastases.
      MATERIALS AND METHODS: Fourteen patients with cerebral metastases underwent
      dynamic CT perfusion scans during palliative whole brain irradiation. Perfusion
      scans were performed on Day 1 prior to initial radiotherapy treatment, then on
      Day 2, and on Day 5 immediately after completion of radiotherapy. Measurements of
      cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT)
      and capillary surface area permeability product (PS) were performed for each
      perfusion scan, and daily symptom assessment was taken prior to initial perfusion
      scan and thereafter prior to each daily radiation treatment. RESULTS: Utilizing
      Day 1 as baseline, a 19% increase (P = 0.033) was noted in PS at Day 2, (median
      1.47 ml/100 g/min), which returned to Day 1 range at Day 5 (median 1.31 ml/100
      g/min). When symptoms were correlated with perfusion parameters, a statistically
      significant association between change in MTT with change in headache scores was
      observed, baseline to Day 2 (P = 0.019), and a trend between change in nausea
      scores with change in CBV (P = 0.059) as well as change in MTT (P = 0.098),
      baseline to Day 5. CONCLUSION: This study has demonstrated the feasibility of a
      non-invasive technique to assess changes occurring within the human brain during
      a course of radiation treatment. Dynamic perfusion tomography provides insight
      into the pathophysiological processes taking place and allows correlation with
      patient symptomatology.

PMID- 15735919
TI  - Distribution of BPA and metabolic assessment in glioblastoma patients during BNCT
      treatment: a microdialysis study.
AB  - Boron neutron capture therapy (BNCT) is dependent on the selective accumulation
      of boron-10 in tumour cells. To maximise the radiation effect, the neutrons
      should be delivered when the ratio between the boron concentration in tumour
      cells to that in normal tissues reaches maximum. However, the pharmacokinetics of
      p-boronophenylalanine (BPA) and other boron delivery agents are only partly
      known. We used microdialysis to investigate the extracellular in vivo kinetics of
      boron in three intracerebral compartments -- solid tumour, brain adjacent to
      tumour (BAT), and the normal brain, as well as the subcutaneous tissue before,
      during, and after BNCT treatment. The findings were compared to the
      pharmacokinetics of BPA in the blood. We also measured the glucose metabolism and
      the levels of glutamate and glycerol in those compartments. Four patients were
      studied, two patients underwent surgical tumour resection and in two a
      stereotactic biopsy was performed. The patients were given BPA (900 mg/kg body
      weight) by a 6-h infusion. The infusion was completed approximately 2-3 h before
      neutron irradiation. In tumour tissue the extracellular concentration of BPA
      followed that of blood with a maximal concentration of 31.2 ppm and a maximal
      ratio vs. blood of 1.07. In BAT, the maximal concentration of BPA was 18.0 ppm
      with the peak level delayed for 4-6 h compared to the peak in blood with a
      maximal ratio of 1.2. Maximal blood concentration found was 41.0 ppm. The uptake
      of BPA in the normal brain was considerably lower than that in the blood and
      tumour tissue. No change in glucose metabolism was observed. The extracellular
      level of glycerol was increased after treatment in tumour tissue but not in
      normal brain suggesting a selective acute cytotoxic effect of BNCT on tumour
      cells.

PMID- 15735920
TI  - UKT-04 trial of continuous metronomic low-dose chemotherapy with methotrexate and
      cyclophosphamide for recurrent glioblastoma.
AB  - Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Continuous
      oral low-dose chemotherapy with methotrexate (MTX) and cyclophosphamide (CPM) has
      modest activity in heavily pretreated patients with breast cancer. We explored
      the efficacy of 100 mg CPM daily and 5 mg MTX twice weekly in relapsed
      glioblastoma. Ten patients, 22-59 years old, with a Karnofsky score of 50% or
      higher who had failed at least two chemotherapies were accrued. No toxicity was
      observed. No patient showed a complete or partial response. Five of 10 patients
      progressed within 2 months of therapy. Another five patients progressed after 3
      4.5 months. The median time to progression was 2.5 months. The median overall
      survival after start of MTX/CPM was 6.9 months (range 0.5-18.8 months). Since the
      progression-free survival rate at 6 months was 0%, the trial was prematurely
      closed.

PMID- 15735921
TI  - A Phase II trial of paclitaxel and topotecan with filgrastim in patients with
      recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.
AB  - PURPOSE: Therapy for high-grade gliomas remains unsatisfactory. Paclitaxel and
      topotecan have separately demonstrated activity against gliomas. We conducted a
      Phase II trial of these agents in combination with filgrastim (G-CSF) in patients
      with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.
      PATIENTS AND METHODS: Adult patients with radiographic evidence of recurrent or
      progressive tumor following primary therapy were eligible for study. Patients
      received paclitaxel 175 mg/m2 IV over 3 h on day 1 and topotecan 1.0 mg/m2 IV
      over 30 min on days 1-5. Filgrastim 5 microg/kg was given days 6-14 for
      neutrophil support. Treatment cycles were repeated every 21 days. RESULTS: Twenty
      patients were enrolled on study, and seventeen were considered evaluable for
      response. Two patients (12/%) exhibited partial remission and seven patients
      (41/%) exhibited stable disease in response to therapy. Hematologic toxicity was
      common with 25 /% of patients experiencing grade III or IV leukopenia despite G
      CSF support. Two patients died of infectious complications on protocol, prompting
      suspension of further accrual. CONCLUSION: Paclitaxel and topotecan with G-CSF
      support exhibits modest activity in adults with recurrent or refractory
      glioblastoma and anaplastic astrocytoma. The significant hematotoxicity
      encountered, however, cannot justify further investigation of this combination in
      patients with high grade brain tumors.

PMID- 15735922
TI  - Gamma Knife radiosurgery for intracranial metastatic melanoma: an analysis of
      survival and prognostic factors.
AB  - Objective of this study was to evaluate retrospectively the effectiveness of
      Gamma Knife radiosurgery for intracranial metastatic melanoma and to identify
      prognostic factors related to survival. Twenty-six patients with intracranial
      metastases (72 lesions) from melanoma underwent Gamma Knife radiosurgery. In 14
      patients (54%) whole-brain radiotherapy (WBRT) was performed as part of the
      initial treatment, and in 12 patients (38%) immunotherapy and/or chemotherapy was
      given after Gamma Knife radiosurgery. The median tumor volume for Gamma Knife
      radiosurgery treated lesions was 1.72 cm3. The median prescribed radiation dose
      was 18 Gy (range 8-22 Gy) typically prescribed to the isodose at the tumor
      margin. Univariate and multivariate analyses were used to determine significant
      prognostic factors affecting survival. Overall median survival was 6 months after
      Gamma Knife radiosurgery, and 1-year survival was 25%. The median survival from
      the onset of brain metastases was 9 months and from the original diagnosis of
      melanoma was 50 months (range 4-160 months). There were no major acute or late
      GKS complications. In univariate testing, the Karnofsky score equal to or higher
      than 90% (P < 0.01, log-rank test), supratentorial localization (P < 0.001, log
      rank test), intracranial tumor volume less than 1 cm3 (P < 0.02, log-rank test),
      and absence of neurological signs or symptoms before Gamma Knife radiosurgery (P
      < 0.003, log-rank test) were significant favorable factors for survival. In
      multivariate regression analyses, the most important predictors associated with
      increased survival were a KPS > or = 90 (P < 0.023), female sex (P < 0.004),
      supratentorial localization (P < 0.01), and absence of neurological symptoms (P <
      0.008). Radiosurgery is a noninvasive, safe, and effective treatment option for
      patients with single or multiple intracranial metastases from melanoma. Female
      sex, Karnofsky score > or = 90, supratentorial localization and lack of symptoms
      before the Gamma Knife radiosurgery were good independent predictors of survival.

PMID- 15735923
TI  - Treatment-related myelodysplastic syndrome after temozolomide for recurrent high
      grade glioma.
AB  - In patients with recurrent malignant glioma, treatment-related myelodysplastic
      syndrome (t-MDS) and acute leukemia are rare adverse effects because the median
      survival after relapse is limited. We report a 44-year-old woman with t-MDS
      (refractory anemia with excess blasts) following treatment of recurrent
      anaplastic astrocytoma with temozolomide (TMZ). A cytogenetic study showed del
      (3)(q11.1). MDS was diagnosed 8.4 months after beginning TMZ. The disease rapidly
      evolved into acute leukemia within 1 month after the onset of MDS, and the
      patient died 1 month later during induction chemotherapy. The prognosis of t-MDS
      is generally poor. Considering the increasing use of TMZ, which is regarded as a
      drug with moderate toxicity, careful follow-up with routine blood testing is
      vital.

PMID- 15735924
TI  - Recurrent low-grade gliomas: the role of fractionated stereotactic re
      irradiation.
AB  - PURPOSE: To assess the effectiveness of re-irradiation in recurrent low-grade
      gliomas (LGG). PATIENTS AND METHODS: Sixty-three patients were treated with
      fractionated stereotactic re-irradiation in the case of recurrent gliomas. At
      primary diagnosis of the tumor, the histology was grade II astrocytoma,
      oligodendroglioma or oligoastrocytoma. Fifty-two (82.5%) recurrences were in
      field, three (4.8%) were localized at the field border, and eight (12.7%) tumors
      were localized completely out-field of the former RT field, respectively. Using
      three to four irregular non-coplanar fields formed with a multi-leaf-collimator,
      we applied a median total dose of 36 Gy (range 15-62 Gy)with a weekly
      fractionation of 5 x 2 Gy/week depending on the size and the location of the
      lesion. No concomitant chemotherapy was applied. RESULTS: Radiation was well
      tolerated by all patients. No severe side effects occurred. Median overall
      survival was 111 months (range 12-240 months). Extent of neurosurgical resection
      significantly influenced overall survival (P = 0.02). Median interval between the
      first radiation therapy and re-irradiation was 50 months (range 5-204 months).
      From the time point of re-irradiation, median survival was 23 months. Median
      progression-free survival from the time point of re-irradiation was 12 months
      (range 2-63 months). No prognosticators could be identified for survival from re
      irradiation and progression free survival. CONCLUSION: Our retrospective data
      suggest that stereotactically guided fractionated re-irradiation in recurrent
      glioma represents an effective treatment option with good results and few
      complications. However, further investigation is warranted to consolidate these
      results and to combine radiation with chemotherapy in the case of recurrent LGG.

PMID- 15735926
TI  - Successful treatment of a chemoresistant tumor with temozolomide in an adult
      patient: report of a recurrent intracranial mesenchymal chondrosarcoma.

PMID- 15735925
TI  - Evaluation of 11C-methionine PET as a surrogate endpoint after treatment of grade
      2 gliomas.
AB  - The aim of the present study was to assess the usefulness of positron emission
      tomography (PET) as a surrogate endpoint by analysing the uptake variability of
      11C-methionine (MET) in follow-up scans.A total of 96 PET MET scans were re
      evaluated in 32 patients with histologically confirmed supratentorial grade 2
      gliomas. In untreated patients, all follow-up PET scans showed an increased
      tumour volume after median 68 weeks, but only 46% of cases had an increased hot
      spot uptake. An improved outcome was observed in patients with stable hot spot
      uptake per se (P = 0.07) and in combinations with minor increase in tumour volume
      (P = 0.02). After conventional therapy, 52% of PET scans showed a reduced hot
      spot uptake the first year and 43% were reduced after more than a year.
      Successful MET decline after therapy did not correlate with outcome. PET MET may
      be a promising surrogate endpoint after treatment of grade 2 gliomas. Evaluation
      of both hot spot activity and uptake volume on PET may strengthen the association
      with clinical outcome.

PMID- 15735927
TI  - Chronic inflammatory polyneuropathy revealing malignant melanoma.

PMID- 15735932
TI  - Differential expression of genes within the cochlea as defined by a custom mouse
      inner ear microarray.
AB  - Microarray analyses have contributed greatly to the rapid understanding of
      functional genomics through the identification of gene networks as well as gene
      discovery. To facilitate functional genomics of the inner ear, we have developed
      a mouse inner-ear-pertinent custom microarray chip (CMA-IE1). Nonredundant cDNA
      clones were obtained from two cDNA library resources: the RIKEN subtracted inner
      ear set and the NIH organ of Corti library. At least 2000 cDNAs unique to the
      inner ear were present on the chip. Comparisons were performed to examine the
      relative expression levels of these unique cDNAs within the organ of Corti,
      lateral wall, and spiral ganglion. Total RNA samples were obtained from the three
      cochlear-dissected fractions from adult CF-1 mice. The total RNA was linearly
      amplified, and a dendrimer-based system was utilized to enhance the hybridization
      signal. Differentially expressed genes were verified by comparison to known gene
      expression patterns in the cochlea or by correlation with genes and gene families
      deduced to be present in the three tissue types. Approximately 22-25% of the
      genes on the array had significant levels of expression. A number of
      differentially expressed genes were detected in each tissue fraction. These
      included genes with known functional roles, hypothetical genes, and various
      unknown or uncharacterized genes. Four of the differentially expressed genes
      found in the organ of Corti are linked to deafness loci. None of these are
      hypothetical or unknown genes.

PMID- 15735935
TI  - Detailed f1, f2 area study of distortion product otoacoustic emissions in the
      frog.
AB  - Distortion product otoacoustic emissions (DPOAEs) are weak sounds emitted from
      the ear when it is stimulated with two tones. They are a manifestation of the
      nonlinear mechanics of the inner ear. As such, they provide a noninvasive tool
      for the study of the inner ear mechanics involved in the transduction of sound
      into nerve fiber activity. Based on the DPOAE phase behavior as a function of
      frequency, it is currently believed that mammalian DPOAEs are the combination of
      two components, each generated by a different mechanism located at a different
      location in the cochlea. In frogs, instead of a cochlea, two separate hearing
      papillae are present. Of these, the basilar papilla (BP) is a relatively simple
      structure that essentially functions as a single auditory filter. A two-mechanism
      model of DPOAE generation is not expected to apply to the BP. In contrast, the
      other hearing organ, the amphibian papilla (AP), exhibits a tonotopic
      organization. In the past it has been suggested that this papilla supports a
      traveling wave in its tectorial membrane. Therefore, a two-mechanism model of
      DPOAE generation may be applicable for DPOAEs from the AP. In the present study
      we report on the amplitude and phase of DPOAEs in the frog ear in a detailed f1,
      f2 area study. The result is markedly different from that in the mammalian
      cochlea. It indicates that DPOAEs generated by neither papilla agree with the two
      mechanism traveling wave model. This confirms our expectation for the BP and does
      not support the hypothesized presence of a mechanical traveling wave in the AP.

PMID- 15735933
TI  - Ouabain induces apoptotic cell death in type I spiral ganglion neurons, but not
      type II neurons.
AB  - Application of ouabain to the intact round-window (RW) membrane of the gerbil
      cochlea induces apoptosis in most spiral ganglion neurons (SGNs), leaving a few
      neurons intact (Schmiedt et al. 2002). Here, physiological measures and
      immunostaining were used to examine the process of SGN degeneration at 3, 6, 12,
      and 24 h, 4 days, and 1 and 5 months after ouabain treatment. The few remaining
      neurons surviving up to 5 months after ouabain treatment were immunoreactive for
      peripherin, a type II neuron marker. Peripherin-positive cell counts indicate
      that about 7% of the SGNs in the gerbil cochlea are type II neurons, and these
      neurons survive intact after ouabain treatment. Ouabain exposure had little
      effect on the outer hair cell and lateral wall systems, even after a 5 month loss
      of auditory-nerve function. The cellular locations of cytochrome c, poly (ADP
      ribose) polymerase (PARP), and activated caspase 3 were examined in control and
      ouabain-treated cochleas. A redistribution of cytochrome c in peripherin-negative
      (type I) neurons was observed at 3 h after ouabain exposure. Degraded PARP and
      activated caspase 3 were also detected in peripherin-negative SGNs at 6 and 24 h
      after treatment, respectively. These results suggest that the redistribution of
      cytochrome c is an early event during apoptosis in type I SGNs and that
      activation of PARP and caspase 3 are associated with apoptosis in these cells.
      Calcineurin and NF-kappaB are two important signaling pathways that may modulate
      cell survival in the central nervous system. Here, we found that calcineurin and
      NF-kappaB selectively labeled type II neurons. It is speculated that the high
      levels of calcineurin and NF-kappaB in type II SGNs, as compared with type I
      SGNs, may play protective roles in enhancing the survival of type II neurons
      exposed to ouabain.

PMID- 15735936
TI  - Hearing in fishes under noise conditions.
AB  - Our current knowledge on sound detection in fishes is mainly based on data
      acquired under quiet laboratory conditions. However, it is important to relate
      auditory thresholds to background noise in order to determine the signal
      detecting abilities of animals in the natural environment. We investigated the
      influence of two noise levels within the naturally occurring range on the
      auditory sensitivity of two hearing specialists (otophysines) and a hearing
      generalist. Audiograms of the goldfish Carassius auratus, the lined Raphael
      catfish Platydoras costatus and the pumpkinseed sunfish Lepomis gibbosus (hearing
      generalist) were determined between 200 and 4000 Hz (100-800 Hz for L. gibbosus)
      under laboratory conditions and under continuous white noise by recording
      auditory evoked potentials (AEPs). Baseline thresholds showed greatest hearing
      sensitivity around 500 Hz in goldfish and catfish and at 100 Hz in the sunfish.
      Continuous white noise of 110 dB RMS elevated the thresholds by 15-20 dB in C.
      auratus and by 4-22 dB in P. costatus. White noise of 130 dB RMS elevated overall
      hearing thresholds significantly in the otophysines by 23-44 dB. In the goldfish,
      threshold did not shift at 4 kHz. In contrast, auditory thresholds in the sunfish
      declined only at the higher noise level by 7-11 dB. Our data show that the AEP
      recording technique is suitable for studying masking in fishes, and that the
      occurrence and degree of the threshold shift (masking) depend on the hearing
      sensitivity of fishes, the frequency, and noise levels tested. The results
      indicate that acoustic communication and orientation of fishes, in particular of
      hearing specialists, are limited by noise regimes in their environment.

PMID- 15735934
TI  - Disruption of lateral olivocochlear neurons via a dopaminergic neurotoxin
      depresses sound-evoked auditory nerve activity.
AB  - We applied the dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) to the guinea pig cochlear perilymph. Immunolabeling of
      lateral olivocochlear (LOC) neurons using antibodies against synaptophysin was
      reduced after the MPTP treatment. In contrast, labeling of the medial
      olivocochlear innervation remained intact. As after brainstem lesions of the
      lateral superior olive (LSO), the site of origin of the LOC neurons, the main
      effect of disrupting LOC innervation of the cochlea via MPTP was a depression of
      the amplitude of the compound action potential (CAP). CAP amplitude depression
      was similar to that produced by LSO lesions. Latency of the N1 component of the
      CAP, and distortion product otoacoustic emission amplitude and adaptation were
      unchanged by the MPTP treatment. This technique for selectively lesioning
      descending LOC efferents provides a new opportunity for examining LOC modulation
      of afferent activity and behavioral measures of perception.

PMID- 15735937
TI  - Noise susceptibility of cochlear implant users: the role of spectral resolution
      and smearing.
AB  - The latest-generation cochlear implant devices provide many deaf patients with
      good speech recognition in quiet listening conditions. However, speech
      recognition deteriorates rapidly as the level of background noise increases.
      Previous studies have shown that, for cochlear implant users, the absence of fine
      spectro-temporal cues may contribute to poorer performance in noise, especially
      when the noise is dynamic (e.g., competing speaker or modulated noise). Here we
      report on sentence recognition by cochlear implant users and by normal-hearing
      subjects listening to an acoustic simulation of a cochlear implant, in the
      presence of steady or square-wave modulated speech-shaped noise. Implant users
      were tested using their everyday, clinically assigned speech processors. In the
      acoustic simulation, normal-hearing listeners were tested for different degrees
      of spectral resolution (16, eight, or four channels) and spectral smearing
      (carrier filter slopes of -24 or -6 dB/octave). For modulated noise, normal
      hearing listeners experienced significant release from masking when the original,
      unprocessed speech was presented (which preserved the spectro-temporal fine
      structure), while cochlear implant users experienced no release from masking. As
      the spectral resolution was reduced, normal-hearing listeners' release from
      masking gradually diminished. Release from masking was further reduced as the
      degree of spectral smearing increased. Interestingly, the mean speech recognition
      thresholds of implant users were very close to those of normal-hearing subjects
      listening to four-channel spectrally smeared noise-band speech. Also, the best
      cochlear implant listeners performed like normal-hearing subjects listening to
      eight- to 16-channel spectrally smeared noise-band speech. These findings suggest
      that implant users' susceptibility to noise may be caused by the reduced spectral
      resolution and the high degree of spectral smearing associated with channel
      interaction. Efforts to improve the effective number of spectral channels as well
      as reduce channel interactions may improve implant performance in noise,
      especially for temporally modulated noise.

PMID- 15735938
TI  - On the coupling between the incus and the stapes in the cat.
AB  - The connection between the long process and the lenticular process of the incus
      is extremely fine, so much so that some authors have treated the lenticular
      process as a separate bone. We review descriptions of the lenticular process that
      have appeared in the literature, and present some new histological observations.
      We discuss the dimensions and composition of the lenticular process and of the
      incudostapedial joint, and present estimates of the material properties for the
      bone, cartilage, and ligament of which they are composed. We present a
      preliminary finite-element model which includes the lenticular plate, the bony
      pedicle connecting the lenticular plate to the long process, the head of the
      stapes, and the incudostapedial joint. The model has a much simplified geometry.
      We present simulation results for ranges of values for the material properties.
      We then present simulation results for this model when it is incorporated into an
      overall model of the middle ear of the cat. For the geometries and material
      properties used here, the bony pedicle is found to contribute significant
      flexibility to the coupling between the incus and the stapes.

PMID- 15735939
TI  - Head-shaking nystagmus depends on gravity.
AB  - In acute unilateral peripheral vestibular deficit, horizontal spontaneous
      nystagmus (SN) increases when patients lie on their affected ear. This phenomenon
      indicates an ipsilesional reduction of otolith function that normally suppresses
      asymmetric semicircular canal signals. We asked whether head-shaking nystagmus
      (HSN) in patients with chronic unilateral vestibular deficit following vestibular
      neuritis is influenced by gravity in the same way as SN in acute patients. Using
      a three-dimensional (3-D) turntable, patients (N = 7) were placed in different
      whole-body positions along the roll plane and oscillated (1 Hz, +/-10 degrees )
      about their head-fixed vertical axis. Eye movements were recorded with 3-D
      magnetic search coils. HSN was modulated by gravity: When patients lay on their
      affected ear, slow-phase eye velocity significantly increased upon head shaking
      and consisted of a horizontal drift toward the affected ear (average: 1.2 degrees
      /s +/-0.5 SD), which was added to the gravity-independent and directionally
      nonspecific SN. In conclusion, HSN in patients with chronic unilateral peripheral
      vestibular deficit is best elicited when they are lying on their affected ear.
      This suggests a gravity-dependent mechanism similar to the one observed for SN in
      acute patients, i.e., an asymmetric suppression of vestibular nystagmus by the
      unilaterally impaired otolith organs.

PMID- 15735940
TI  - Molecular, biochemical, and physiological approaches for understanding the
      ecology of denitrification.
AB  - One of the major challenges in microbial ecology for the future is to establish
      links between structural and functional biodiversity. This is particularly
      difficult when one is interested in a phylogenetically diversified function such
      as denitrification. The data banks are very rich in functional gene sequences
      (nirS in this study), but most of them were obtained from not yet cultivated
      bacteria, and thus must be supplemented by sequences of organisms from the
      environment for which we could associate a taxonomic position and physiological
      characteristics. Combined analysis including molecular (16S-rRNA or nirS genes),
      physiological, and biochemical approaches was carried out on a bacterial set of
      89 strains isolated from marine sediment. The denaturing gradient gel
      electrophoresis (DGGE) technique was successfully applied on unclamped polymerase
      chain reaction (PCR) products of nirS genes to compare the picture of the
      biodiversity obtained with 16S rRNA and nirS genes. The diversity of nirS genes
      and denitrifier characteristics were found within several of the 16S rDNA
      phylotypes. In contrast, the nirS phylotypes were no diverse both with respect to
      16S rDNA and to physiology and biochemistry of denitrification. Sequences of the
      nirS PCR products were very close to marine environmental clones and were
      analyzed within the same phylogenetic tree.

PMID- 15735941
TI  - Enrichment of anammox from activated sludge and its application in the CANON
      process.
AB  - A microbial culture capable of actively oxidizing ammonium to dinitrogen gas in
      the absence of oxygen, using nitrite as the electron acceptor, was enriched from
      local activated sludge (Western Australia) in <14 weeks. The maximum anaerobic
      ammonium oxidation (i.e., anammox) activity achieved by the anaerobic culture was
      0.26 mmol NH (4) (+) (g biomass)(-1) h(-1) (0.58 kg total-N m(-3) day(-1)).
      Qualitative FISH analysis (fluorescence in situ hybridization) confirmed the
      phylogenetic position of the enriched microorganism as belonging to the order
      Planctomycetales, in which all currently identified anammox strains fall.
      Preliminary FISH analysis suggests the anammox strain belongs to the same
      phylogenetic group as the Candidatus 'Brocadia anammoxidans' strain discovered in
      the Netherlands. However, there are quite a few differences in the target sites
      for the more specific probes of these organisms and it is therefore likely to
      represent a new species of anammox bacteria. A small amount of aerobic ammonium
      oxidizing biomass was inoculated into the anammox reactor (10% v/v) to initiate
      completely autotrophic nitrogen removal over nitrite (the CANON process) in
      chemostat culture. The culture was always under oxygen limitation and no organic
      carbon was added. The CANON reactor was operated as an intermittently aerated
      system with 20 min aerobiosis and 30 min anaerobiosis, during which aerobic and
      anaerobic ammonium oxidation were performed in sequential fashion, respectively.
      Anammox was not inhibited by repeated intermittent exposure to oxygen, allowing
      sustained, completely autotrophic ammonium removal (0.08 kg N m(-3) day(-1)) for
      an extended period of time.

PMID- 15735945
TI  - Infrarenal abdominal aortic aneurysm repair via endovascular versus open
      retroperitoneal approach.
AB  - The beneficial effects of open surgical abdominal aortic aneurysm (AAA) repair
      via a left retroperitoneal approach have been established. We compared the short
      term outcome of infrarenal AAA repair via an endovascular approach with that of
      an open retroperitoneal approach. From October 2001 to April 2003, patients with
      infrarenal AAA >5 cm were offered repair via an endovascular approach (group I)
      with a variety of industry-made stent grafts or with an open retroperitoneal
      surgical approach (group II). Data were prospectively collected in the vascular
      registry and complications were analyzed. Data comparison between the two groups
      was done by using chi-squared analysis and two-tailed Students t-test.
      Statistical significance was identified at p < 0.05. Over an 18-month period, 492
      patients underwent evaluation for AAA. Of these, 446 patients had infrarenal AAA
      and underwent either endovascular (group I: n = 175, male 85%, female 15%) or
      open surgical repair (group II: n = 232, male 74%, female 26%) via a left
      retroperitoneal approach. Group I patients had a higher incidence of coronary
      artery disease (66% vs. 35%, p < 0.05), hypertension (74% vs. 43%, p < 0.05),
      chronic obstructed pulmonary disease (29% vs. 12%, p < 0.05), and diabetes
      mellitus (20% vs. 7%, p < 0.05), a lower mean amount of intraoperative blood loss
      (277 cc vs. 1452 cc, p < 0.05), and shorter length of stay in the hospital (1.7
      days vs., 7.3 days, p < 0.05). Group I also had fewer complications of myocardial
      infarction (1.7% vs. 5.2%, p = NS), renal failure (0% vs. 2.6%, p < 0.05),
      pulmonary failure (1.7% vs. 2.6%, p = NS), ischemic colitis requiring colectomy
      (0.6% vs. 2.6%, p < 0.05), multisystem organ failure (0% vs. 1.3%, p = NS), and
      death (0.6% vs. 1.3%, p < 0.05). Despite increased preexisting comorbidities,
      patients undergoing endovascular aneurysm repair had less morbidity, mortality,
      and blood loss and a shorter in-hospital length of stay than patients undergoing
      open surgical aneurysm repair via a left retroperitoneal approach.

PMID- 15735946
TI  - Acute aortic dissection presenting with primarily abdominal pain: a rare
      manifestation of a deadly disease.
AB  - The objective of this study was to determine the morbidity and mortality of
      patients with acute thoracic aortic dissections who present primarily with
      abdominal pain. Nine hundred ninety-two patients (mean age, 62.1 years +/- 14.1;
      68% male) encountered from 1996 to 2001 with acute thoracic aortic dissections
      from the International Registry of acute Aortic Dissection were studied. Patient
      demographics, presenting symptoms, signs of aortic dissection, aortic pathology,
      and mortality were compared in patients presenting primarily with abdominal pain
      (group I, 46 patients, 4.6%) versus all others (group II). Demographics were
      similar between the two groups. When signs of aortic dissection were examined,
      63% of patients in group I presented with hypertension compared to only 47% of
      patients in group II (p = 0.04). Patients in group I were less likely to present
      with evidence of end-organ malperfusion. Importantly, mortality in patients with
      a type B dissection, specifically following surgery for the dissection, was
      significantly increased in patients who presented primarily with abdominal pain
      (group I, 28% mortality vs. group II, 10.2% mortality; p = 0.02). This study
      documented increased mortality in patients with acute thoracic aortic dissections
      who present primarily with abdominal pain, underscoring the importance of
      maintaining a high index of suspicion for an aortic dissection in patients who
      have appropriate risk factors.

PMID- 15735947
TI  - Percutaneous and open renal revascularizations have equivalent long-term
      functional outcomes.
AB  - Atherosclerotic renal artery stenosis is a significant cause of poorly controlled
      hypertension and progressive renal dysfunction leading to ischemic nephropathy
      and other end-organ damage. The optimal treatment of renovascular disease
      contributing to hypertension and renal dysfunction is not known. This study
      compares the anatomic and functional outcomes of both open and endovascular
      therapy for chronic, symptomatic atherosclerotic renal artery disease. We
      performed a retrospective analysis of records from patients who underwent renal
      arterial interventions, endovascular or open bypass, between January 1984 and
      January 2004. Principal indications for intervention were hypertension (51%),
      chronic renal insufficiency (13%), and hypertension and elevated creatinine
      (36%). A total of 247 patients (109 males; mean age 69 +/- 10, range 44-89 years)
      underwent 314 interventions (109 open procedures; 205 angioplasties, 71% with
      stent placement). There was a significant difference in 30-day mortality (4% vs.
      <1%; p < 0.005) between the open and endoluminal groups, but not at 1, 3, or 5
      years. Patients in the open group had a higher primary patency rate at 5 years
      (83 +/- 5% vs. 76 +/- 6%; p = 0.03), but patients in the endoluminal group had a
      higher assisted primary patency rate at 5 years (92 +/- 5% vs. 84 +/- 5; p =
      0.03). There was no significant difference between both treatment groups in
      cumulative freedom from presenting symptom or in freedom from dialysis and renal
      related death. Patients who presented with hypertension were more likely to have
      shown improvement in their blood pressure with endoluminal intervention at 1, 3,
      and 5 (59 +/- 6% endoluminal vs. 83 +/- 5% open; p = 0.01) years. From these
      results we conclude that open repair and endoluminal repair of atherosclerotic
      renal artery stenosis have similar immediate and long-term functional and
      anatomic outcomes. Patients who present with hypertension may have greater
      benefit with an endoluminal repair.

PMID- 15735948
TI  - Surgical management of renal fibromuscular dysplasia: challenges in the
      endovascular era.
AB  - Percutaneous transluminal renal angioplasty (PTRA) is the primary treatment for
      renal fibromuscular dysplasia (RFMD). Surgical revascularization is limited to
      patients who fail or are unsuitable for PTRA. All patients who were operated on
      with RFMD since the indications for renal PTRA were expanded in our institution
      were retrospectively reviewed. Outcome included patency, hypertension, and renal
      function. Twenty-six patients had reconstruction of 32 renal arteries between
      1998 and 2004. The mean age was 47.1 +/- 14 years; the majority (81%) were
      female. Six patients had bilateral disease and three had a solitary kidney.
      Operations were done for hypertension in 25 patients, renal artery aneurysm in 8,
      and chronic dissection in 1, alone or in combination. Six patients had a failed
      PTRA and 20 were unsuitable for it. Aortorenal bypass was done most often (n =
      28) and saphenous vein was the preferred conduit (n = 25). The distal anastomosis
      was to the main renal artery in 13 patients and to the branch arteries in 19. Ex
      vivo repair was needed in five patients. Five intraoperative revisions were done
      because of abnormalities on duplex scan. One patient died unexpectedly 42 days
      after operation from myocardial infarction. Extrarenal complications occurred in
      five patients. Median follow-up was 2.4 (range, 42 days to 6.3) years and was
      available in all but one patient (96%). Two bypasses occluded at 3 and 376 days,
      which resulted in loss of the kidneys. One graft stenosis was treated
      successfully with PTRA at 239 days. All failures occurred in men. One-year
      cumulative primary patency was 89 +/- 8% and was not adversely affected by prior
      PTRA or complex repair. Hypertension at 1 year was cured in 27% of the patients
      and improved in 60%. No patient developed acute or chronic renal failure.
      Surgical reconstruction for RFMD has excellent short-term patency. Failed PTRA or
      complex reconstructions did not adversely affect outcome.

PMID- 15735949
TI  - [Clear cell tumor of the lung].
AB  - Clear cell tumors of the lung are rare tumors composed of epithelioid HMB45
      positive tumor cells. It has been proposed that clear cell tumors generate from
      perivascular epithelioid cells which are also found in renal angiomyolipoma. Due
      to its morphologic epithelioid features with clear cytoplasm the distinction from
      either primary or metastatic clear cell carcinoma is difficult. Usually clinical
      investigations do not lead to the final diagnosis so that only subsequent
      histological examination and immunophenotyping can establish the correct tumor
      classification. We describe the case of a 52 year old woman who underwent
      exploratory thoracotomy because of a lung mass in the right lower lobe. In frozen
      sections a solid trabecular tumor was diagnosed, paraffin histology and
      immunohistochemistry revealed a clear cell tumor of the lung. The difficulty of
      the correct diagnosis of the clear cell tumor of the lung in frozen sections is
      discussed as well as the differential diagnosis.

PMID- 15735950
TI  - Constant and severe involvement of Betz cells in corticobasal degeneration is not
      consistent with pyramidal signs: a clinicopathological study of ten autopsy
      cases.
AB  - This report concerns a clinicopathological study of three additional patients
      with corticobasal degeneration (CBD), described here for the first time, and a
      clinicopathological correlation between pyramidal signs and upper motor neuron
      involvement, in ten autopsy cases of CBD, including seven cases reported by us
      previously. We investigated pyramidal signs, including hyperreflexia, Babinski
      sign, and spasticity, and involvement of the primary motor cortex and pyramidal
      tract, focusing on the astrocytosis of the fifth layer of the primary motor
      cortex. Pyramidal signs were observed in six (60%) of the ten cases.
      Hyperreflexia was evident in six patients (60%), with spasticity being observed
      in three patients (30%). Loss of Betz cells associated with prominent
      astrocytosis and presence of ballooned neurons in the fifth layer of the primary
      motor cortex was observed in all ten cases. In all cases, involvement of the
      pyramidal tract was obvious in the medulla oblongata, without involvement of the
      pyramidal tract in the midbrain. Constant and severe involvement of the fifth
      layer of the primary motor cortex, including the Betz cells, has not previously
      been reported in CBD. We suggest that the pyramidal signs in CBD have been
      disregarded.

PMID- 15735951
TI  - Bipolar radiofrequency-induced thermotherapy (rfitt) for the treatment of
      spasmodic dysphonia. A report of three cases.
AB  - The symptoms of adductor spasmodic dysphonia are most commonly palliated by
      periodic botulinum toxin injections. The need for repeated injections, difficulty
      in obtaining injections and cost make this form of treatment intolerable for some
      patients. To address these concerns, we propose a new treatment approach
      utilizing trans-oral recurrent nerve coagulation. The goal is to weaken the force
      of laryngeal closure during spasms by creating fibrosis of the terminal branches
      of one recurrent nerve through coagulation. Under general anesthesia without
      paralysis, an electrical stimulator is used to identify the region within the
      thyroarytenoid muscle that produces the greatest contraction with minimal
      stimulation. The radiofrequency laryngeal probe or electrocautery device is
      introduced into this position, and energy is delivered. The location of the
      region of maximal stimulation is usually just lateral and anterior to the vocal
      process of the arytenoids. Between 1989 and 2000, seven patients were treated
      with electrocautery. To achieve remission of spasms, three patients needed three
      sessions, four needed two sessions and one only one session. Since 2001, three
      patients have achieved remission of spasms with a single treatment with
      radiofrequency during which 80 J was delivered. Voice results are comparable to
      those obtained with botulinum toxin. Initially, the voice is breathy and
      laryngeal examination shows complete vocal fold immobility. After 1-2 months, the
      voice improves and examination reveals unilateral hypomobility. Trans-oral
      recurrent nerve coagulation is an effective alternative to botulinum toxin
      injections.

PMID- 15735952
TI  - Three-slice computerized tomography for the diagnosis and follow-up of
      rhinosinusitis.
AB  - Plain sinus radiography is the imaging technique most frequently used to
      investigate suspected rhinosinusitis, but it has low diagnostic sensitivity.
      Contiguous paranasal computerized tomography (CT) gives detailed information
      about the pathology, anatomy and anatomical variations of the paranasal sinuses,
      but this method also has limitations. The cost of using this technique for all
      cases of suspected rhinosinusitis is prohibitive, and complete CT scans involve
      considerable radiation exposure. The aim of this study was to devise a CT
      protocol for diagnosing and following rhinosinusitis that is more economical and
      involves much less radiation exposure than contiguous CT. In this retrospective
      study, three physicians independently reviewed the contiguous coronal paranasal
      CT studies of 136 patients. The study population comprised the adult patients who
      were investigated for suspected chronic rhinosinusitis. All scans had been
      obtained at the second visit, after the patient had completed a 3-week course of
      medical treatment. For each case, the same three slices were selected to form the
      "three-slice CT" exam, and the same physicians independently evaluated this set.
      Using the results from the contiguous set as the gold standard, we calculated the
      sensitivity and specificity of three-slice CT for identifying rhinosinusitis. The
      sensitivity and specificity of three-slice CT for identifying inflammatory sinus
      disease were 95.1 and 92.6%, respectively. Three-slice CT is a valuable method
      for diagnosing and following rhinosinusitis cases, and would be cheaper and
      involve less radiation exposure than contiguous coronal CT. However, despite the
      high cost and greater radiation exposure, contiguous CT remains the gold standard
      for evaluating detailed sinus anatomy and disease progression.

PMID- 15735953
TI  - Nasal foreign body in an adult.
AB  - Foreign bodies of the nose in adults are rare, although they are frequently
      encountered among children and mentally retarded patients. They are often
      asymptomatic and consequently may remain undetected for many years. We describe a
      case of an intranasal foreign body mimicking a nasal lesion.

PMID- 15735954
TI  - Feasibility of acrylic acid production by fermentation.
AB  - Acrylic acid might become an important target for fermentative production from
      sugars on bulk industrial scale, as an alternative to its current production from
      petrochemicals. Metabolic engineering approaches will be required to develop a
      host microorganism that may enable such a fermentation process. Hypothetical
      metabolic pathways for insertion into a host organism are discussed. The pathway
      should have plausible mass and redox balances, plausible biochemistry, and
      plausible energetics, while giving the theoretically maximum yield of acrylate on
      glucose without the use of aeration or added electron acceptors. Candidate
      metabolic pathways that might lead to the theoretically maximum yield proceed via
      beta-alanine, methylcitrate, or methylmalonate-CoA. The energetics and enzymology
      of these pathways, including product excretion, should be studied in more detail
      to confirm this. Expression of the selected pathway in a host organism will
      require extensive genetic engineering. A 100,000-tons/year fermentation process
      for acrylic acid production, including product recovery, was conceptually
      designed based on the supposition that an efficient host organism for acrylic
      acid production can indeed be developed. The designed process is economically
      competitive when compared to the current petrochemical process for acrylic acid.
      Although the designed process is highly speculative, it provides a clear
      incentive for development of the required microbial host, especially considering
      the environmental sustainability of the designed process.

PMID- 15735955
TI  - Denitrifying activity of Xanthobacter autotrophicus strains isolated from a
      submerged fixed-film reactor.
AB  - Xanthobacter autotrophicus strains with the ability to reduce nitrate and nitrite
      to either nitrous oxide or molecular nitrogen were isolated from submerged fixed
      film reactors. Isolated strains were Gram-negative rods able to grow on methanol,
      ethanol and sucrose. The yellow cellular pigmentation, pleomorphic appearance,
      and the presence of poly-beta-hydroxybutyrate granules suggest that the organisms
      might belong to the genus Xanthobacter. Comparison of 16S rDNA gene sequences
      demonstrated the affiliation of the strains to X. autotrophicus species. The
      results show that X. autotrophicus may play a role in inorganic nitrogen removal
      from a denitrifying submerged filter used for the treatment of contaminated
      groundwater. To our knowledge, no data on denitrifying activity in X.
      autotrophicus strains have been reported previously.

PMID- 15735956
TI  - Usefulness of serum mast cell-specific chymase levels for postmortem diagnosis of
      anaphylaxis.
AB  - Chymase, a serine protease, is stored mainly in secretory granules of human mast
      cells. Serum chymase concentration was examined in 8 autopsy cases with
      anaphylaxis as well as in 104 control cases without anaphylaxis. It was detected
      in all 8 cases with anaphylaxis (range 3-380 ng/ml, mean 89.8 ng/ml), while it
      was detected in only 2 of the 104 controls and was below a detectable level (<3
      ng/ml) in the other 102. Serum tryptase levels are known to be a diagnostic
      indicator of anaphylaxis, therefore the relationship between serum chymase and
      tryptase levels was investigated in the 8 cases of anaphylactic death; a
      significant positive correlation was found (r=0.826, p=0.011). Furthermore,
      chymase was shown to be quite stable in serum. These results showed that
      measurement of serum chymase levels might be an additional tool for postmortem
      diagnosis of anaphylaxis.

PMID- 15735957
TI  - Julia Bell and the Treasury of Human Inheritance.
AB  - The Treasury of Human Inheritance represents the most extensive, and one of the
      earliest series of documentations and analyses of human genetic disorders.
      Published between 1909 and 1958, from The Galton Laboratory, London, most of the
      numerous sections were written by Julia Bell, who represents a key figure in the
      development of human and medical genetics. Her combination of mathematical
      training, genetic knowledge and clinical expertise yielded numerous important
      insights into human inheritance first appearing in the Treasury; it remains a
      valuable scientific as well as an historical record of the genetics of a range of
      important inherited disorders.

PMID- 15735959
TI  - Competitive reactions of a ruthenium arene anticancer complex with histidine,
      cytochrome c and an oligonucleotide.
AB  - The ruthenium arene anticancer complex [(eta(6)-bip)Ru(en)Cl][PF(6)] (1) (bip is
      biphenyl, en is ethylenediamine) reacted slowly with the amino acid L-histidine
      (L-His) in aqueous solution at 310 K. Two L-His adducts of 1 were separated by
      high-performance liquid chromatography and identified by electrospray ionisation
      mass spectrometry and NMR: an imidazole N(delta)-bound complex [(eta(6)
      bip)Ru(en)(N(delta)-L-His)](2+), and an N(epsilon)-bound complex [(eta(6)
      bip)Ru(en)(N(epsilon)-L-His)](2+). At 310 K, after 24 h only about 22% of complex
      1 (2 mM) reacted with L-His, and of the unreacted 1, 59% had hydrolysed. In the
      presence of 100 mM NaCl, approximately 90% of 1 remained unreacted. In aqueous
      solution or triethylammonium acetate (TEAA) buffer (pH 7.6), (15)N-labelled 1
      reacted with cytochrome c to give two monoruthenated protein adducts. The
      reaction reached equilibrium within 2 h by which time approximately 50% of
      cytochrome c was ruthenated. On the basis of [(1)H, (15)N] NMR data, one adduct
      may have Ru bound to the N-terminus, and the other to a carboxylate group on the
      protein. In TEAA buffer and at 310 K, more than 90% of the 14-mer oligonucleotide
      d(TATGTACCATGTAT) reacted with 2 mol Eq of 1 to give rise to monoruthenated and
      diruthenated oligonucleotide adducts. The presence of cytochrome c (1 mol Eq) or
      L-His (4 mol Eq) had little effect on the course of the reaction with the
      oligonucleotide. In cells, DNA (or RNA) may be a favoured reaction site for this
      Ru anticancer complex.

PMID- 15735961
TI  - Somatic DNA oxidative damage and coronary disease.

PMID- 15735960
TI  - Effects of activation of central nervous histamine receptors in cardiovascular
      regulation; studies in H(1) and H(2) receptor gene knockout mice.
AB  - To elucidate the central roles of histamine receptors in cardiovascular
      regulatory system, systolic, mean, and diastolic blood pressures (BPs) and heart
      rate (HR) were examined in conscious H(1) receptor gene knockout (H(1)KO) mice,
      H(2) receptor gene knockout (H(2)KO) mice, H(1) and H(2) receptor gene double
      knockout (DKO) mice, and their respective control mice by the tail-cuff system.
      Histamine, histamine-trifluoromethyl-toluidine derivative (HTMT, an H(1)
      agonist), dimaprit (an H(2) agonist), and immepip (an H(3) agonist) were
      intrathecally administered to these KO mice and control mice. Basal BPs and HR
      were not different among these three KO mice and their control or wild-type mice.
      Intrathecal administration of histamine significantly increased BPs and decreased
      HR in control mice. The increases in BPs were produced by histamine in H(1)KO and
      H(2)KO mice and by HTMT and dimaprit in C57BL mice. The pressor responses by HTMT
      and dimaprit in C57BL mice were greater than those by histamine in H(1)KO and
      H(2)KO mice, although the same decreases in HR were induced by histamine in C57BL
      and H(1)KO mice and by dimaprit in C57BL mice. The selective stimulation of H(3)
      receptors by immepip produced a consistent decrease in BPs in control mice. These
      results obtained with the exogenous selective agonists of three histamine
      receptors suggest that the pressor responses to histamine are mediated through
      the stimulation of both H(1) and H(2) receptors, whereas the atropine-sensitive
      decrease in heart rate is mainly due to H(2) receptors which activate the vagal
      output to the heart.

PMID- 15735963
TI  - A case report of midgut atresia and spontaneous closure of gastroschisis.
AB  - We report a case in which a neonate with a prenatal diagnosis of gastroschisis
      was born with midgut atresia and the mummified remains of the midgut arising from
      a spontaneously closed abdominal wall defect. As our ability to prenatally
      diagnose abdominal wall defects has improved, we have gained some insight into
      the prenatal natural history of this pathological process. We present a case in
      which an abdominal wall defect spontaneously closed and was associated with an
      apparent in utero midgut vascular accident. This unusual case provides some
      insight into the mechanisms underlying the pathophysiology of gastroschisis.

PMID- 15735962
TI  - Evaluation of thrombotic children with malignancy.
AB  - The purpose of this study was to evaluate inherited and acquired prothrombotic
      risk factors among children with malignancies who have thrombosis and emphasize
      the importance of inherited prothrombotic risk factors. Thirty-seven consecutive
      children with thrombosis and malignancy were included in this study. The patients
      were evaluated separately for time of development of thrombosis, insertion of a
      central venous line (CVL), history of L: -asparaginase usage, and recent
      infections. Prothrombotic risk factors such as factor V G1691A and prothrombin
      G20210A mutation, protein C, protein S, antithrombin III deficiencies, factor
      VIII and lipoprotein(a) elevation, and antiphospholipid antibodies were analyzed
      for all patients. Of 387 children with thrombosis, 37 (9.5%) had a malignancy.
      Thrombosis was detected in 9 patients at the time of diagnosis, during
      maintenance therapy in 25 patients, and after the discontinuation of treatment in
      3 patients. One or two additional prothrombotic risk factors other than L: 
      asparaginase therapy and insertion of central venous lines were present in 20 of
      these patients (54%). It was found that eight patients had the factor V G1691A
      mutation in the heterozygote state. One of them had the factor V G1691A mutation
      associated with a history of infection and one patient had the factor V G1691A
      mutation associated with factor VIII elevation. One had the the prothrombin
      G20210A mutation in the heterozygote state, four had lipoprotein(a) elevation,
      two had factor VIII elevation, one had a decreased protein S level, one had a
      decreased protein C level, one had antiphospholipid positivity, and two had
      histories of infection. Malignancy is an important risk factor for the
      development of childhood thrombosis. However, the risk of thrombosis increases
      when accompanied by additional prothrombotic risk factors. For this reason,
      especially children with malignancy and at high risk for the development of
      thrombosis, such as those who have received L: -asparaginase or a replaced CVL
      during their therapy, might be screened for additional prothrombotic risk factors
      and appropriate measures might be taken to prevent the development of thrombosis.

PMID- 15735964
TI  - The effect of extracellular calcium concentration on calcium-mediated cell
      signaling in NF1 tumor suppressor-deficient keratinocytes.
AB  - Capacitative calcium entry and calcium wave propagation were studied in
      keratinocytes from healthy volunteers and patients with type 1 neurofibromatosis
      (NF1) in calcium-depleted and in low calcium culture medium. In previous studies,
      we found evidence that mutations of the NF1 tumor suppressor gene can lead to
      altered calcium-mediated cell signaling in keratinocytes cultured in the presence
      of a high extracellular calcium concentration. The present study demonstrated
      that the differences between normal and NF1 keratinocytes were dependent on
      extracellular calcium concentration. Specifically, when keratinocytes were
      exposed to thapsigargin under calcium-depleted culture conditions the subsequent
      increase in free intracellular calcium concentration was moderate in NF1
      keratinocytes compared to controls. The finding indicates lowered endoplasmic
      calcium stores in NF1 which may also in part explain the reduced activation
      signal for capacitative calcium influx and the wound-induced intracellular Ca2+
      transient observed in NF1 keratinocytes maintained in culture medium containing
      0.05 mM calcium. The differences between control and NF1 keratinocytes were most
      pronounced when the cells were cultured in the presence of a high (1.8 mM)
      calcium concentration. Since elevated extracellular calcium levels induce
      keratinocytes to form cellular contacts and lead to terminal differentiation,
      markedly aberrant responses of NF1 keratinocytes in the presence of a high
      calcium concentration may help to explain previous findings on impaired formation
      of cellular junctions and differentiation in NF1 deficient cells.

PMID- 15735965
TI  - Wood adhesives prepared from lucerne fiber fermentation residues of Ruminococcus
      albus and Clostridium thermocellum.
AB  - Fermentation residues (consisting of incompletely fermented fiber, adherent
      bacterial cells, and a glycocalyx material that enhanced bacterial adherence)
      were obtained by growing the anaerobic cellulolytic bacteria Ruminococcus albus 7
      or Clostridium thermocellum ATCC 27405 on a fibrous fraction derived from lucerne
      (Medicago sativa L.). The dried residue was able to serve as an effective co
      adhesive for phenol-formaldehyde (PF) bonding of aspen veneer sheets to one
      another. Testing of the resulting plywood panels revealed that the adhesive,
      formulated to contain 30% of its total dry weight as fermentation residue,
      displayed shear strength and wood failure values under both wet and dry
      conditions that were comparable with those of industry standards for PF that
      contained much smaller amounts of fillers or extenders. By contrast, PF adhesives
      prepared with 30% of dry weight as either unfermented lucerne fiber or
      conventional fillers or extenders rather than as fermentation residues, displayed
      poor performance, particularly under wet conditions.

PMID- 15735966
TI  - Molecular and functional characterization of a levansucrase from the sourdough
      isolate Lactobacillus sanfranciscensis TMW 1.392.
AB  - Exopolysaccharides (EPS) produced in situ by sourdough lactobacilli affect
      rheological properties of dough as well as bread quality and may serve as
      prebiotics. The aim of this study was to characterize EPS-formation by
      Lactobacillus sanfranciscensis TMW 1.392 at the molecular level. A levansucrase
      gene from L. sanfranciscensis TMW 1.392 encompassing 2,300 bp was sequenced. This
      levansucrase is predicted to be a cell-wall associated protein of 879 amino acids
      with a relative molecular weight (M(R)) of 90,000. The levansucrase gene was
      heterologously expressed in Escherichia coli and purified to homogeneity. The
      recombinant enzyme exhibited transferase and hydrolase activities and produced
      glucose, fructose, 1-kestose and levan from sucrose; truncation of the N-terminal
      domain did not affect catalytic activity. Kestose formation was enhanced relative
      to fructose and levan formation by low temperature or high sucrose levels. During
      growth in wheat doughs, strain TMW 1.392 utilized sucrose to form fructose, 1
      kestose, and fructan, whereas a levansucrase deletion mutant, L. sanfranciscensis
      TMW 1392Deltalev, lost the ability to hydrolyze sucrose, and did not produce
      fructan or 1-kestose. These results indicate that, in L. sanfranciscensis TMW
      1.392, sucrose metabolism and formation of fructan and 1-kestose is dependent on
      the activity of a single enzyme, levansucrase.

PMID- 15735967
TI  - A Gluconobacter oxydans mutant converting glucose almost quantitatively to 5-keto
      D-gluconic acid.
AB  - Gluconobacter oxydans converts glucose to gluconic acid and subsequently to 2
      keto-D-gluconic acid (2-KGA) and 5-keto-D-gluconic acid (5-KGA) by membrane-bound
      periplasmic pyrroloquinoline quinone-dependent and flavin-dependent
      dehydrogenases. The product pattern obtained with several strains differed
      significantly. To increase the production of 5-KGA, which can be converted to
      industrially important L-(+)-tartaric acid, growth parameters were optimized.
      Whereas resting cells of G. oxydans ATCC 621H converted about 11% of the
      available glucose to 2-KGA and 6% to 5-KGA, with growing cells and improved
      growth under defined conditions (pH 5, 10% pO2, 0.05% pCO2) a conversion yield of
      about 45% 5-KGA from the available glucose was achieved. As the accumulation of
      the by-product 2-KGA is highly disadvantageous for an industrial application of
      G. oxydans, a mutant was generated in which the membrane-bound gluconate-2
      dehydrogenase complex was inactivated. This mutant, MF1, grew in a similar way to
      the wild type, but formation of the undesired 2-KGA was not observed. Under
      improved growth conditions, mutant MF1 converted the available glucose almost
      completely (84%) into 5-KGA. Therefore, this newly developed recombinant strain
      is suitable for the industrial production of 5-KGA.

PMID- 15735968
TI  - The ability of white-rot fungi to degrade the endocrine-disrupting compound
      nonylphenol.
AB  - Phanerochaete chrysosporium, Pleurotus ostreatus, Trametes versicolor and
      Bjerkandera sp. BOL13 were tested for their ability to degrade the endocrine
      disrupting compound nonylphenol at an initial concentration of 100 mg l-1. The
      highest removals were achieved with T. versicolor and Bjerkandera sp. BOL13,
      which were able to degrade 97 mg l-1 and 99 mg l-1 of nonylphenol in 25 days of
      incubation, respectively. Nonylphenol removal was associated with the production
      of laccase by T. versicolor, but the levels of laccase, manganese peroxidase and
      lignin peroxidase produced by Bjerkandera sp. BOL13 were very low. At 14 degrees
      C, T. versicolor and Bjerkandera sp. BOL13 sustained the removal of 88 mg l-1 and
      79 mg l-1 of nonylphenol, respectively. No pollutant removal was recorded at 4
      degrees C, although both fungi could grow at this temperature in the absence of
      nonylphenol. A microtoxicity assay showed that the fungi produced compounds that
      were toxic to Vibrio fischerii; and thus a reduction in toxicity could not be
      correlated with nonylphenol metabolism. T. versicolor and Bjerkandera sp. BOL13
      were capable of colonizing soil artificially contaminated with 430 mg kg-1 of
      nonylphenol. Only 1.3+/-0.1% of nonylphenol remained in the soil after 5 weeks of
      incubation.

PMID- 15735969
TI  - Planispheric multiplanar reformatted CT: a new method for evaluation of
      paediatric congenital spine abnormalities.
AB  - We describe an original reconstruction method for spine CT performed in four
      patients with single or multiple congenital spine abnormalities. Conventional
      radiographic imaging is at the forefront of diagnosis and follow-up of congenital
      scoliosis, but is frequently difficult to interpret. Three-dimensional CT
      reconstruction facilitates visualization of complex anatomic structures, but does
      not give a reliable assessment of failures of segmentation. Mental three
      dimensional reconstruction of the information displayed by classical multiplanar
      reformatted CT remains difficult. Planispheric reformatted imaging allows the
      visualization of all deformities in a single plane.

PMID- 15735970
TI  - Cantu syndrome.

PMID- 15735971
TI  - International Consensus on Nasal Polyposis 2002-2004.
AB  - Seventeen well-known experts in rhinosinusology from various countries tried to
      achieve consensus on the etiology, conservative approach and surgical approach to
      nasal polyposis. A Digi-Vote electronic system was used for an immediate computer
      analysis of expert answers to 23 questions related to the problem of nasal
      polyposis.

PMID- 15735972
TI  - Swallowing function in patients with multiple-system atrophy with a clinical
      predominance of cerebellar symptoms (MSA-C).
AB  - We investigated the swallowing function of 21 patients with multiple system
      atrophy with a clinical predominance of cerebellar symptoms (MSA-C) by
      videofluoroscopy (VF). Twenty-six VF examinations were performed at various time
      points, and they were divided into three groups according to the duration
      following disease onset: Group A had 1 to 3 years following disease onset (the
      early stage of the disease), group B had 4 to 6 years following disease onset
      (the middle stage of the disease), and group C had more than 7 years following
      disease onset (the late stage of the disease). Swallowing function in the oral
      phase became gradually disturbed over the progression of MSA. Delayed bolus
      transport from the oral cavity to the pharynx was already seen in 50% of the
      patients in group A, and it was seen in more than 85% of the patients in group C.
      Bolus holding in the oral cavity was slightly disturbed in group A, but it was
      seen in 57% of the patients in group C. Our study shows that parkinsonism is
      related to swallowing dysfunction in MSA, but cerebellar dysfunction also affects
      coordination of the tongue; bolus transport in the oral cavity was disturbed in
      the early stage of disease. Progression of cerebellar dysfunction and overlapped
      parkinsonism will worsen tongue movement, and in the late stage of the disease,
      swallowing function of the oral phase (bolus transport and bolus holding) was
      remarkably disturbed. Swallowing function in the pharyngeal phase was not
      significantly correlated to the duration of the disease; however, our study
      showed that swallowing function in the pharyngeal phase was not assessed fully by
      VF examination in MSA-C only. Combination with other examinations, such as
      manometry and electromyography, may be useful, especially in the late stage of
      the disease. In addition, an analysis concerning the relationship between
      aspiration seen on VF examination and a history of aspiration pneumonia in MSA-C
      patients suggested that the sensory system at the larynx and trachea should also
      be assessed in patients in the late stage of MSA-C.

PMID- 15735973
TI  - Paroxysmal positional vertigo as a complication of osteotome sinus floor
      elevation.
AB  - Paroxysmal positional vertigo (PPV) is a high prevalence, vestibular end organ
      disorder due to the detachment of the utricular otoconia floating in the
      posterior or lateral semicircular canal. Even though in the majority of cases the
      etiology of PPV is unknown, it may follow viral infection, vascular disorders and
      head trauma after different surgical procedures. The aim of this study was to
      investigate the correlation between PPV and the surgical trauma induced by the
      vibratory and percussive forces on the upper maxilla during the osteotome sinus
      floor elevation procedure. We performed a complete otoneurological examination on
      146 patients affected by atrophic ridges before and after upper maxilla surgery.
      Four patients showed a PPV of the posterior semicircular canal controlateral to
      the implanted side 1 or 2 days after the surgical procedure, which promptly was
      solved with the Epley re-positioning maneuver. We hypothesize that the surgical
      trauma, and specifically the pressure exerted by the osteotomes, determines the
      detachment of the otoliths from the utricular macula while the patient head
      position, hyper-extended and tilted opposite to the side where the surgeon is
      working, favors the entry of these free-floating particles in the posterior
      semicircular canal of the implanted side. Although this disease is rather
      frequent in the normal population and it is a benign, self-limiting peripheral
      disorder, it should be considered by the oral surgeon as a possible complication
      of pre-prosthetic upper maxilla surgery, and the patient should be informed
      before undergoing surgery.

PMID- 15735974
TI  - Craniocervical junction venous anatomy around the suboccipital cavernous sinus:
      evaluation by MR imaging.
AB  - The present study evaluated the venous anatomy of the craniocervical junction,
      focusing on the suboccipital cavernous sinus (SCS), a vertebral venous plexus
      surrounding the horizontal portion of the vertebral artery at the skull base. MR
      imaging was reviewed to clarify the venous anatomy of the SCS in 33 patients.
      Multiplanar reconstruction MR images were obtained using contrast-enhanced three
      dimensional fast spoiled gradient-recalled acquisition in the steady state (3-D
      fast SPGR) with fat suppression. Connections with the SCS were evaluated for the
      following venous structures: anterior condylar vein (ACV); posterior condylar
      vein (PCV); lateral condylar vein (LCV); vertebral artery venous plexus (VAVP);
      and anterior internal vertebral venous plexus (AVVP). The SCS connected with the
      ACV superomedially, with the VAVP inferolaterally, and with the AVVP medially.
      The LCV connected with the external orifice of the ACV and superoanterior aspect
      of the SCS. The PCV connected with the posteromedial aspect of the jugular bulb
      and superoposterior aspect of the SCS. The findings of craniocervical junction
      venography performed in eight patients corresponded with those on MR imaging,
      other than with regard to the PCV. Contrast-enhanced 3-D fast SPGR allows
      visualization of the detailed anatomy of these venous structures, and this
      technique facilitates interventions and description of pathologies occurring in
      this area.

PMID- 15735975
TI  - Ammonium affects tight junctions and the cytoskeleton in MDCK cells.
AB  - In the kidney medulla, tubule cells are exposed not only to elevated NaCl but
      also to high NH(4)Cl concentrations. Although it is well known that long-term
      exposure to high NaCl concentrations leads to reorganization of the actin-based
      cytoskeleton and to altered transport properties of renal epithelial cells, there
      have been no comparable studies on the effects of elevated extracellular NH(4)Cl
      concentrations. We therefore examined the effect of prolonged (up to 72 h)
      exposure of Madin-Darby canine kidney (MDCK) cells to increased NH(4)Cl
      concentrations on the actin-based cytoskeleton, the transepithelial electrical
      resistance (TER) and the expression and intracellular distribution of the tight
      junction protein occludin. NH(4)Cl exposure resulted in rarefaction of
      cytoplasmic stress fibres, formation of intense peripheral actin bands and
      reduced abundance of both F- and G-actin. While under control conditions occludin
      staining was restricted to the tight junction region, ample dot-like
      intracellular staining was apparent after NH(4)Cl exposure. These changes in cell
      structure were associated with an increase in TER and the enhanced expression of
      an additional putative, 40-kDa occludin isoform. Exposure to elevated
      extracellular NH(4)Cl concentrations thus leads to distinct alterations in the
      architecture and transepithelial transport properties of MDCK cells that may also
      be relevant for the tubule cells of the renal inner medulla.

PMID- 15735976
TI  - Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to
      cancer predisposition in hereditary non-polyposis colon cancer.
AB  - The majority of tumours in patients with hereditary non-polyposis colon cancer
      (HNPCC) occur in large intestine and endometrium; also, other tissues are at
      increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal
      samples of various tissues from non-HNPCC patients and in 14 normal colon tissues
      from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear
      staining, percentage of stained cells and H-scores were calculated. Tissues were
      divided into groups. Groups A, B and C included tissues with increased risk of
      cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary,
      ureter, urinary bladder, kidney and liver. Group D tissues were without increased
      risk. Expression of the proteins was significantly higher in groups A, B and C
      compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The
      expression was highest in testis. In colons of HNPCC patients, expression of the
      mutated gene product was significantly lower than in non-HNPCC patients. In
      conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain
      cell types of certain tissues, including the majority of tissues that are at
      increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2
      expression with cancer risk is not strictly valid.

PMID- 15735977
TI  - Hypermethylation of Chfr and hMLH1 in gastric noninvasive and early invasive
      neoplasias.
AB  - Human tumors are genetically unstable, and the instability exists at two distinct
      levels-the chromosomal level and the nucleotide level. Chfr and hMLH1
      hypermethylation, which may lead to chromosomal instability (CIN) and
      microsatellite instability (MSI), respectively, was analyzed in gastric
      noninvasive neoplasias (NIN, Padova international classification) and submucosal
      invasive adenocarcinomas and in their corresponding non-neoplastic gastric
      epithelia. Results were compared with microsatellite status, p53
      immunoreactivity, and cellular phenotype. Hypermethylation of Chfr and hMLH1 was
      observed in: 10% (1/10) and 0% (0/10) of low-grade NIN (L-NIN); 63% (5/8) and 63%
      (5/8) of high-grade NIN, including suspicion for carcinoma without invasion (H
      NIN); 36% (5/14) and 57% (8/14) of high-grade NIN, including carcinoma without
      invasion; and 35% (7/20) and 25% (5/20) of submucosal invasive adenocarcinomas,
      respectively. Hypermethylation was less frequent in L-NIN than H-NIN (P<0.05) for
      Chfr and was also less frequent in L-NIN than the others (P<0.05) for hMLH1. We
      failed to find a significant correlation between Chfr hypermethylation and
      chromosomal loss of heterozygosity, although hypermethylation of hMLH1 was
      significantly associated with high-frequency MSI (P<0.01). Expression of p53 was
      not associated with Chfr or hMLH1 methylation. As for cellular phenotype,
      hypermethylation of Chfr and hMLH1 was frequent in tumors exhibiting the foveolar
      epithelial phenotype (50%, 2/4 and 75%, 3/4, respectively) and the ordinary
      phenotype (40%, 16/40 and 38%, 15/40, respectively), but never in those with the
      complete-type intestinal metaplastic phenotype (0%, 0/8 for both). In addition,
      hypermethylation of Chfr and hMLH1 occurred concurrently (P<0.01); methylation
      was more frequent in patients over 70 years of age (P<0.01), and it was also
      present in some samples of non-neoplastic gastric epithelia from elderly
      patients. Thus, some gastric tumors with the foveolar or ordinary phenotype may
      develop as a result of age-related methylation of Chfr and hMLH1, although Chfr
      methylation was not associated with CIN.

PMID- 15735978
TI  - Aggressive angiomyxoma: a clinicopathological and immunohistochemical study of 11
      cases with long-term follow-up.
AB  - AIMS: To report the clinicopathological and immunohistochemical features and
      longer term biological behaviour of aggressive angiomyxoma, an uncommon
      mesenchymal neoplasm occurring predominantly in the pelvi-perineal region of
      adults. Using immunohistochemistry, possible overexpression of CDK4 and MDM2 was
      analysed, which might point to (cyto)genetic alteration(s) in chromosome region
      12q13-15, an area reported to be altered in this tumour entity. METHODS AND
      RESULTS: Cases (n=11) of aggressive angiomyxoma were retrieved from the
      consultation files of the Comprehensive Cancer Centre of the Middle Netherlands
      (IKMN) panel for soft tissue tumours. Clinical and follow-up information were
      obtained, and immunohistochemical analysis was performed using antibodies
      directed against vimentin, cytokeratin AE1/AE3, desmin, alpha-smooth-muscle
      actin, CD34, S-100 protein, oestrogen receptors, CDK4 and MDM2. Five patients
      were female (age range 24-47 years; median 39 years), and six patients were male
      (age range 36-69 years; median 44.5 years). Of 11 cases, 10 arose in the pelvi
      perineal area and 1 arose in the abdominal cavity in close relation to the
      bladder. Morphology was consistent with previous reports of this entity.
      Immunohistochemically, 8 of 11 cases were desmin positive (5 of 5 positive in
      females; 3 of 6 positive in males), 6 of 11 cases were positive for alpha-smooth
      muscle actin, 5 of 11 cases were CD34 positive, 11 of 11 cases, irrespective of
      gender, were positive for oestrogen receptors and 3 of 11 cases were positive for
      cytokeratin AE1/AE3. Strong, diffuse nuclear positivity for CDK4 expression was
      present in all 6 cases tested, while only 1 of 11 cases tested for MDM2 showed
      weak focal positivity. Clinical follow-up in all cases (range 1-216 months;
      median 72 months) showed one local recurrence (9%) after 36 months. No metastases
      or tumour-related deaths were noted. CONCLUSIONS: The sex distribution of cases
      reported in this study was roughly equal, in contrast to previous reports
      emphasising the predominance of this tumour in females. Our study confirms the
      local aggressive nature of aggressive angiomyxoma, although our local recurrence
      rate is lower than previous reports (9% versus 36-72%); no metastases and/or
      disease-related patient deaths were documented. All cases arising in females were
      positive for desmin, while three of the six cases arising in males were negative
      for desmin, supporting previous findings and indicating that the lesion may be
      somewhat different in males. The strong diffuse positivity for CDK4 in all six
      cases tested goes some way in implicating CDK4, either directly or indirectly, in
      tumourigenesis. The negative immunostaining for MDM2 would argue against
      functional amplification of this gene.

PMID- 15735979
TI  - Role of pathology in the identification of hereditary diffuse gastric cancer:
      report of a Portuguese family.
AB  - Mutations in E-cadherin gene are the underlying genetic defect in approximately
      one-third of the hereditary diffuse gastric cancer (HDGC) families described to
      date. Positive family history of diffuse gastric cancer and early age of onset of
      gastric tumours are the clinical criteria currently used to qualify for HDGC. In
      the present study, we describe a Portuguese family with HDGC that was selected
      for CDH1 mutation screening after histological observation of the gastrectomy
      specimen of one member, who died at the age of 23 years from widely invasive
      diffuse gastric carcinoma. The detection in the surgical specimen of tiny foci of
      intramucosal diffuse carcinoma as well as in situ carcinoma lesions and pagetoid
      spread of signet ring cells raised the hypothesis of HDGC, which was confirmed by
      pedigree analysis of the family and detection of CDH1 germline mutation. We
      conclude that there are morphological hints that may help in the identification
      of HDGC.

PMID- 15735980
TI  - Pericardial ectopic thymoma.
AB  - Primary intrapericardial thymoma is an unusual localization. We report a case of
      a patient with an isolated and primary pericardial thymoma. This 72-year-old
      woman presented with dyspnea, dysphony and myalgia. The radiological evaluation
      revealed an intrapericardial mass. Surgical exploration showed a hemorrhagic and
      infiltrative tumor in the pericardial sac, while the mediastinum was free of
      tumor. Surgical biopsies and, later, an ablation of pericardial mass were done.
      The tumor was a thymoma, composed of large epithelial cells and immature T
      lymphocytes and was classified B2 according to the World Health Organization
      classification (1999). Clinically, a myasthenia gravis was revealed. We discuss
      the few cases reported in the literature.

PMID- 15735981
TI  - Peripheral ameloblastoma with Merkel cells.

PMID- 15735983
TI  - Research advances in amyotrophic lateral sclerosis (ALS): a personal view.

PMID- 15735984
TI  - [Diagnosis of middle cerebral artery spasm by determination of flow velocity and
      the Lindegaard index with transcranial color Doppler sonography].
AB  - BACKGROUND AND PURPOSE: Recent reports have demonstrated the high utility of
      transcranial color-coded duplex sonography (TCCS) in the diagnosis of advanced
      spasm of the middle cerebral artery, whereas its accuracy in the diagnosis of
      mild vasospasm is reported to be lower. Relation of blood flow velocity in the
      middle cerebral artery (MCA) to that in the extracranial internal carotid artery
      (VMCA/VICA index) is recommended as being helpful in the diagnosis of vasospasm
      (the so called Lindegaard Index). Nevertheless, the exact diagnostic value of
      this index using the TCCS method remains to be established. The purpose of this
      study is to estimate the accuracy of TCCS in the diagnosis of MCA vasospasm, as
      based on the VMCA/VICA index. MATERIAL AND METHODS: The VMCA/VICA index was
      calculated in 195 patients (285 middle cerebral arteries) who were scheduled for
      cerebral arteriography. The TCCS study and color-coded duplex sonography of the
      internal carotid arteries were performed immediately before arteriography.
      RESULTS: A mild grade of MCA spasm was diagnosed angiographically in 21, and
      moderate-to-severe spasm in 29 MCAs out of 285 successfully insonated arteries.
      Peak-systolic, mean and end-diastolic blood velocities were measured using
      transcranial color sonography in the MCA and related to the respective velocities
      in the ipsilateral extracranial internal carotid artery. Receiver-operating
      characteristic curves (ROC) were calculated for particular velocities and for the
      related VMCA/VICA indices. By comparison of the areas under the ROC curves it was
      shown that the use of the VMCA/VICA index does not improve the accuracy of TCCS
      in the diagnosis of advanced MCA spasm, whereas it improves accuracy in the
      diagnosis of mild vasospasm. In particular, accuracy can be improved by the use
      of the VMCA/VICA index based on the end-diastolic velocity. The optimal
      diagnostic threshold of the VMCA/VICA index was determined at 3.9. CONCLUSIONS:
      The use of VMCA/VICA index improves the accuracy of TCCS in the diagnosis of mild
      vasospasm of the middle cerebral artery.

PMID- 15735985
TI  - [Endoscopic transsphenoidal treatment of pituitary adenomas].
AB  - BACKGROUND AND PURPOSE: The aim of this study is to present a new endoscopic
      transnasal transsphenoidal method of surgical treatment of pituitary adenomas and
      to evaluate the results and complications of the method. MATERIAL AND SURGICAL
      TECHNIQUE: From October 2001 to June 2003 in the Department of Neurosurgery of
      the Medical University of Silesia in Katowice 88 operations of pituitary adenomas
      were performed using the transnasal transsphenoidal endoscopic method. The group
      of patients consisted of 50 females and 38 males. The youngest patient was 11
      years old and the oldest was 79 years old. Patients were operated on using the 4
      mm diameter endoscope with 0- and 30-degree angled lenses, using a method of
      operation according to Jho and Carrau with own modifications. At the time of
      surgery the operation team included 2 neurosurgeons, an anesthesiologist and a
      laryngologist. RESULTS: In the group of 51 nonfunctioning adenomas, in 32 cases
      we obtained the total removal of the tumor, which amounts to 63%. Among 37 of
      hyperfunctioning adenomas there were 11 prolactinomas, 19 GH secreting adenomas
      and 7 ACTH secreting adenomas. In all cases of prolactinomas the tumor was
      removed totally and in the cases of GH secreting adenomas and ACTH secreting
      adenomas the total removal of the tumor was performed in 58% and 86% of the
      cases, respectively. One patient within our group died after the operation. It
      was the patient with a huge nonfunctioning macroadenoma, with hydrocephalus and
      preoperative disturbances of consciousness. The permanent diabetes insipidus
      occurred in 2 cases, which amounts to 2.3% of all operated patients. In this
      group we noticed the intraoperative CSF leakage in 20 cases but we did not
      observe the postoperative CSF leakage or any rhinological complications.
      CONCLUSIONS: The endoscopic transnasal transsphenoidal approach is an efficient
      method of surgical treatment of pituitary adenomas. The advantage of this method
      is low invasiveness and a small number of serious complications.

PMID- 15735987
TI  - [Surgical treatment of brainstem gliomas and other tumors in adults].
AB  - BACKGROUND AND PURPOSE: After the introduction of MR imaging to the diagnostics
      of brainstem tumors and after the introduction of microsurgical procedures to
      their treatment, the successful treatment, particularly of focal and exophytic
      forms of these tumors has begun all over the world. The objective of this paper
      is to establish indications for surgical treatment of gliomas and other tumors of
      brainstem, to determine surgical approaches and to establish the outcome.
      MATERIAL AND METHODS: Within the last 6 years, 12 patients with focal and
      exophytic tumors of the brainstem in adults were operated on. 5 tumors were
      located in the midbrain, 4 in the pons, 2 in the medulla oblongata and 1 was a
      cervicomedullary one. With one exception, all tumors were approached via the
      posterior fossa. RESULTS: The total removal was performed in 75% and a subtotal
      one in 25% of cases. A serious complication in 2 patients was bilateral ptosis
      after the removal of midbrain tumors. This lesion gradually regressed. A similar
      dangerous complication is impaired swallowing and coughing reflex loss which, by
      exposing the patient to the risk of aspiration pneumonia, occurred in 2 patients.
      One of these patients died after the operation. CONCLUSIONS: Patients with focal
      and exophytic forms of the brainstem tumors in MR imaging are qualified for
      surgical treatment. Immediate results of the treatment depend on the localization
      and size of the neoplasm. A precise operative approach, use of the
      neurophysiological examination and postoperative care at the Intensive Care Unit
      are essential conditions to obtain good results of the operative treatment.

PMID- 15735989
TI  - [Effects of intracranial hypertension on gastric myoelectrical activity evaluated
      by using clinical and radiological symptoms].
AB  - BACKGROUND AND PURPOSE: Acute and chronic increases in intracranial pressure
      (ICP) cause a dramatic autonomic dysfunction. The aim of the study is to evaluate
      effects of acute and chronic ICP on gastric myoelectrical activity. MATERIAL AND
      METHODS: We studied 80 patients hospitalized in the Department of
      Neurotraumatology of the Jagiellonian University Medical College. The control
      group included 16 healthy volunteers matched with gender and age. Gastric
      myoelectrical activity was captured with cutaneous electrodes and Synectics
      (Sweden) system of storing and analyzing the data. RESULTS: Results of the study
      were analyzed in the Department of Pathophysiology of the Jagiellonian University
      Medical College. Most significant changes on gastric myoelectrical activity were
      observed in patients after a severe head injury with acute intracranial
      hypertension (Glasgow Coma Scale: 4-7 points). The percentage of bradygastria
      timing increased up to 50%. In this group of patients the increase in amplitude
      of the signal was observed. Significant dysrhythmias up to 40% occurred in
      patients with chronic increase of intracranial pressure caused by brain tumors.
      CONCLUSIONS: Most significant changes on gastric myoelectrical activity were
      observed in patients after a severe head injury with acute intracranial
      hypertension (Glasgow Coma Scale: 4-7 points). The percentage of bradygastria
      timing increased up to 50%. Gastric dysmotility was caused by stimulation of both
      arms of the autonomic nervous system.

PMID- 15735988
TI  - [Concentration of interleukin-18, interleukin-1beta, soluble receptor for
      interleukin-1 (sIL-1RII) and C-reactive protein in patients with
      neuroborreliosis].
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to determine the role of
      interleukin-18 (IL-18), interleukin-1beta (IL-1beta) and its soluble receptor sIL
      1RII in the pathogenesis of neuroborreliosis as well as the usefulness of C
      reactive protein (CRP) determination in the diagnosis and monitoring of treatment
      of Lyme neuroborreliosis. MATERIAL AND METHODS: The study group consisted of 20
      patients with Lyme meningitis (age range 16-72 years, mean age 42.6 years). For
      measurements of IL-18, IL-1beta and sIL-1RII levels in serum and cerebrospinal
      fluid (CSF) the control group consisted of 10 healthy volunteers and 10 patients
      with infection of the central nervous system ruled out, respectively. Cytokines
      and sIL-1RII levels in serum and CSF were measured twice, before and after the 30
      day treatment period. Serum and CSF levels of IL-18, IL-1beta and sIL-1RII were
      measured using ELISA, and CRP serum levels were measured using the
      immunoturbidimetric method. RESULTS: Before the treatment the concentration of IL
      18, IL-1beta and sIL-1RII in serum as well as in CSF was significantly higher as
      compared to the controls. After the treatment end the level of IL-18, IL-1beta
      and sIL-1RII was reduced but the serum level of sIL-1RII and CSF level of IL-18
      and sIL-1RII remained significantly higher than in the control group. The serum
      level of CRP was increased only in 15% of patients and after the treatment CRP
      concentration returned to a basal level (except one patient in whom CRP was
      slightly higher than in the control group). No correlation between CRP and IL-18,
      IL-1beta and sIL-1RII was observed. CONCLUSIONS: Our results confirm the
      involvement of IL-18, IL-1beta and sIL-1RII in the pathogenesis of
      neuroborreliosis and uselessness of CRP determination in the diagnosis of Lyme
      meningitis.

PMID- 15735990
TI  - [Meningo-orbital fold (MOF) as a guiding point in extradural approach to the
      anterior clinoid process].
AB  - BACKGROUND AND PURPOSE: The essential stage of Dolenc's approach to the cavernous
      sinus is the incision of the meningo-orbital fold (MOF) without damaging nervous
      structures in the superior orbital fissure. The goal of the research is to
      perform a topographic and morphometric study of the meningo-orbital fold.
      MATERIAL AND METHODS: Formalin preserved central cranial base specimens from
      twenty adults (40 sides) were dissected for this study. The dissection was based
      on Dolenc's epidural approach to the cavernous sinus. RESULTS: The average width
      of MOF is 8.4 mm on the right side and 8.3 mm on the left side. The meningo
      orbital artery (MOA) is an important reference point in recognizing the superior
      orbital fissure. In 75% (15 specimens) of cases the meningo-orbital artery passes
      by the superior fissure at a distance of a few millimeters. In 25% (5 specimens)
      of cases the MOA passes through the lateral margin of the superior orbital
      fissure. CONCLUSIONS: The MOF is an inset of the external layer of the dura mater
      of the middle cranial fossa which passes through the superior orbital fissure and
      joins the periorbita at the level of the sphenoparietal sinus. The average width
      of the MOF is 8.4 mm on the right side and 8.3 mm on the left side. The new
      approach to the safe incision of the MOF relies on the medial margin
      identification by splitting both layers in the lateral wall of the cavernous
      sinus between V1 and V2. After identification of the medial margin, it is
      possible to separate the margin from the superficial layer of the cavernous
      sinus, from the side anterior and middle cranial fossae. It is then possible to
      perform a safe incision of the MOF without any danger of damaging the nerves.

PMID- 15735991
TI  - [Difficulties in microsurgical treatment of aneurysms after coiling].
AB  - BACKGROUND AND PURPOSE: The paper presents our own experience with microsurgical
      clipping of the cerebral aneurysms previously treated using endovascular
      techniques. MATERIAL AND METHODS: The presented clinical material consists of 3
      patients treated in such a way. A group of 60 patients was embolized. An initial
      satisfactory effect of endovascular treatment was verified within 12 months of
      observation. Control radiological examinations--plane skull x-ray and cerebral
      angiography (DSA)--revealed coil displacement and recanalization of the aneurysm.
      In each case a surgical clipping of the aneurysms was performed. RESULTS: Proper
      clipping of previously coiled aneurysms sometimes presents a serious problem.
      Certain difficulties included rebuilding of the aneurysmal wall with a change of
      anatomical configuration in vessel ramifications. CONCLUSIONS: Qualification for
      endovascular treatment and the existing risk of introduction of additional coils
      into the aneurysm sac was discussed in connection with our observations. Problems
      concerning surgical treatment of initially embolized cerebral aneurysms were
      discussed and illustrated. Radiological monitoring of patients after endovascular
      treatment was proposed.

PMID- 15735992
TI  - [Role of matrix metalloproteinases in the pathogenesis of multiple sclerosis].
AB  - Multiple sclerosis (MS) is an autoimmune disease whose features include a massive
      lymphocyte recruitment into the central nervous system and segmental
      demyelinization of the white matter. One of the MS development factors is an
      increase of matrix metalloproteinases (MMPs) activity with a coincidental
      decrease of tissue inhibitors of MMPs (TIMPs) activity. Investigations of serum,
      cerebrospinal fluid and brain tissue of patients showed an increase of MMP-1, -2,
      -3, -7, -9 and MMP-12 activity. MMPs disrupt the blood-brain barrier (BBB),
      increase lymphocyte migration into the central nervous system and are involved in
      degradation of myelin proteins. MMPs induce the appearance of an active form of
      tumor necrosis factor alpha, a strong proinflammatory cytokine. The drugs used in
      MS treatment decrease MMPs expression. Multiple actions of MMPs prove their
      involvement in the pathogenesis and treatment of MS.

PMID- 15735993
TI  - [Surgical technique in operations for brainstem gliomas].
AB  - The article presents an MRI-based classification of brainstem gliomas into focal,
      cervicomedullary, dorsal exophytic and diffuse ones. This classification provides
      the basis for specifying indications for surgical treatment and outcome. The
      article also presents the most frequent approaches to the midbrain, pons and
      medulla oblongata. These approaches include the pterional, orbito-zygomatic,
      subtemporal transtentorial and supracerebellar approaches to the midbrain.
      Suboccipital, trans fourth ventricle, subtonsillar, retrosigmoid and anterior
      petrosal approaches were used in the case of the pons. Suboccipital, trans fourth
      ventricle and transcondylar approaches were applied for the removal of tumors of
      medulla oblongata. This paper elaborates on rare approaches: transcondylar,
      paramedian-supracerebellar, subtonsillar and anterior petrosal ones effectively
      applied in our clinic. The resection of brain stem tumors is performed by
      piecemeal resection and not by removal en bloc. We stress the significance of
      safe entry zones to the brain stem and places at the fossa rhomboidea whose
      impairment may cause severe disability. Lesion of trigonum nervi hypoglossi,
      trigonum nervi vagi, colliculus facialis and fasciculus longitudinalis medialis
      leads to severe disability or death of the patient.

PMID- 15735995
TI  - [Hypnic headache as a primary short-lasting night headache: a report of two
      cases].
AB  - Hypnic headache is a rare type of primary short-lasting headache related to
      sleep. The pathogenesis of hypnic headache still remains unknown, but it may be a
      chronobiological disturbance or a response to a pineal circadian irregularity in
      which melatonin may play a role in resynchronizing biological rhythms to
      lifestyle. It is a moderate headache that appears during sleep with almost an
      alarm clock regularity and lasts up to 60 minutes. The headache is boring,
      unilateral or with diffuse location. Lithium carbonate and flunarizine show the
      best efficacy, caffeine and melatonin may also be useful. The author describes
      two cases of hypnic headache, which were effectively treated. A 45-year-old woman
      was treated with flunarizine and melatonin and a 65-year-old man was treated with
      flunarizine. The efficacy of flunarizine may be associated with the activation of
      D2 receptor and the added treatment with melatonin may hasten the good effect
      similar to that seen in our patient.

PMID- 15735996
TI  - [Satellite Symposium Treating MS: today, tomorrow and in the future, 20th ECTRIMS
      Congress, Vienna (Austria), 8 October 2004, a report].

PMID- 15735997
TI  - Cardiovascular health and fitness after stroke.
AB  - Stroke patients have profound cardiovascular and muscular deconditioning, with
      metabolic fitness levels that are about half those found in age-matched sedentary
      controls. Physical deconditioning, along with elevated energy demands of
      hemiparetic gait, define a detrimental combination termed diminished
      physiological fitness reserve that can greatly limit that can greatly limit
      performance of activities of daily living. The physiological features that
      underlie worsening metabolic fitness in the chronic phase of stroke include gross
      muscular atrophy, altered muscle molecular phenotype, increased intramuscular
      area fat, elevated tissue inflammatory markers, and diminished peripheral blood
      flow dynamics. Epidemiological evidence further suggests that the reduced
      cardiovascular fitness and secondary biological changes in muscle may propagate
      components of the metabolic syndrome, conferring added morbidity and mortality
      risk. This article reviews some of the consequences of poor fitness in chronic
      stroke and the potential biological underpinnings that support a rationale for
      more aggressive approaches to exercise therapy in this population.

PMID- 15735998
TI  - Aerobic exercise training in stroke survivors.
AB  - Functional aerobic capacity among persons with stroke is severely compromised and
      may limit their full participation in community living. Even though aerobic
      conditioning can be potentially valuable to persons with stroke in reducing the
      risk of recurrent morbid events and improving overall quality of life, there is
      limited information on the specific dose of aerobic exercise (i.e., frequency,
      intensity, duration, and modality) that may achieve the most desirable health
      outcomes under the safest conditions in this population. Because of the many
      comorbidities associated with stroke (i.e., hypertension, heart disease, obesity,
      depression), specific recommendations for prescribing aerobic exercise must
      become more precise and be subsequently added to the treatment regimen for this
      large and diverse population. Future research must address optimal aerobic
      training programs necessary for reductions in cardiovascular risk factors and
      gains in functional status in stroke patients.

PMID- 15735999
TI  - Exercise capacity and cardiovascular adaptations to aerobic training early after
      stroke.
AB  - Clinicians are becoming increasingly interested in the use of aerobic training to
      enhance functional outcomes after stroke. Several studies have demonstrated the
      effectiveness of training among individuals in the chronic poststroke period.
      However, there is limited information on the response to training in earlier
      stages of recovery. The purpose of this article is to review what is known
      regarding the capacity of people early after stroke (<4 months) to respond to the
      physiological demands of exercise (exercise capacity) as well as their ability to
      make long-term cardiovascular adaptations to aerobic exercise. There is evidence
      that exercise capacity, as measured by peak oxygen consumption on maximal
      exercise tests, is reduced in this population. There is also evidence, albeit
      limited, that exercise trainability soon after stroke can be both feasible and
      safe, if appropriate screening and monitoring are used. Moreover, there are early
      indications that activity-level functions such as walking speed, mobility, and
      balance may be enhanced through such programs. Further research is necessary to
      elucidate the most appropriate timing and design of fitness programs for people
      early after stroke.

PMID- 15736000
TI  - Task-oriented aerobic exercise in chronic hemiparetic stroke: training protocols
      and treatment effects.
AB  - Stroke is the leading cause of disability in older Americans. Each year 750,000
      Americans suffer a stroke, two thirds of whom are left with neurological deficits
      that persistently impair function. Principal among them is hemiparetic gait that
      limits mobility and increases fall risk, promoting a sedentary lifestyle. These
      events propagate disability by physical deconditioning and "learned non-use,"
      with further functional declines accelerated by the sarcopenia and fitness
      decrements of advancing age. Conventional rehabilitation care typically provides
      little or no structured therapeutic exercise beyond the subacute stroke recovery
      period, based on natural history studies showing little or no further functional
      motor recovery beyond 6 months after stroke. Emerging evidence suggests that new
      models of task-oriented exercise have the potential to improve motor function
      even years after stroke. This article presents treadmill as a task-oriented
      training paradigm to optimize locomotor relearning while eliciting cardiovascular
      conditioning in chronic stroke patients. Protocols for exercise testing and
      longitudinal aerobic training progression are presented that provide fundamental
      formulas that safely approach the complex task of customizing aerobic training to
      gait deficit severity in the high CVD risk stroke population. The beneficial
      effects of 6 months task-oriented treadmill exercise on cardiovascular-metabolic
      fitness, energy cost of hemiparetic gait, ADL mobility task performance, and leg
      strength are discussed with respect to the central and peripheral neuromuscular
      adaptations targeted by the training. Collectively, these findings constitute one
      initial experience in a much broader neuroscience and exercise rehabilitation
      development of task-oriented training paradigms that offer a multisystems
      approach to improving both neurological and cardiovascular health outcomes in the
      chronic stroke population.

PMID- 15736001
TI  - Exercise-induced changes of the upper extremity in chronic stroke survivors.
AB  - Problems with daily activities due to decreased aerobic capacity and decreased
      strength are common in people who survive a stroke. Implementation of exercise
      for the upper extremity is challenging because of weakness and other impairments
      that limit performance of exercise activities. Although maximal exercise testing
      protocols are difficult to administer, submaximal testing may be a safe and
      effective means for prescribing exercise. Research studies have demonstrated that
      people with stroke can improve aerobic capacity and upper extremity muscle
      strength with exercise intervention, although the number of randomized controlled
      trials is limited and this area requires further investigation.

PMID- 15736002
TI  - Applying the transtheoretical model to the exercise behaviors of stroke patients.
AB  - Individuals with disabilities, including stroke, are frequently deconditioned. A
      variety of factors, including infrequent exercise participation, may be
      responsible for the deconditioning observed. According to the transtheoretical
      model (TTM), individuals progress through cognitive processes, termed stages,
      that indicate their readiness to undertake a particular healthy behavior, such as
      exercise. Our study examined 178 community-dwelling stroke patients' readiness to
      initiate an exercise program and their current exercise patterns. Using the
      Stages of Change Questionnaire, we found over 75% of respondents to be in the
      exercise preadoption stages of precontemplation, contemplation, or preparation.
      Moreover, participants classified in the postadoption stages of maintenance and
      action reported exercising significantly more than those in the preadoption
      stages. Individuals in the postadoption stages were also participating in
      significantly more sessions of strenuous or moderate exercise than those in the
      preadoption stages. It was concluded that the TTM is a valid theoretical
      framework to measure stroke patients' readiness to participate in exercise.
      However, additional research examining the psychosocial and functional factors
      mitigating these attitudes, and the stability of these attitudes, needs to be
      performed.

PMID- 15736003
TI  - Laterality of motor control revisited: directionality of callosal traffic and its
      rehabilitative implications.
AB  - Based on evidence derived from personal data and a comprehensive review of the
      literature, this article provides a perspective of laterality of motor control in
      humans. The evidence supports existence of directionality in callosal traffic,
      codified in handedness. However, it is the neural handedness that definitively
      reveals the directionality of signal traffic between the executive and the minor
      hemisphere; the minor hemisphere is devoted to the affairs occurring on or toward
      the nondominant side of the body. Thus, moving the nondominant side of the body
      (and sensing from it) are bi-hemispherical events that require callosal
      participation. Time-resolved data are provided that indicate the absence of any
      ipsilateral corticospinal tract innervation in humans. The rehabilitative aspects
      of the new circuitry (i.e., one-way callosal traffic scheme) is reviewed,
      establishing that previously described plasticity or reorganization of cortical
      structure was a reflection of the newly described anatomy underpinning
      handedness. The distinction between neural and behavioral handedness is
      emphasized, suggesting simple and robust ways to establish a person's handedness
      without resorting to invasive and inconclusive tests currently in vogue. In the
      past, lack of knowledge of directionality in callosal traffic has resulted in
      surgical removal of healthy hemispheres (including the major hemisphere) in
      futile attempts to stop epilepsy in those with an intractable condition. Evidence
      is provided for lack of any motor communication from the minor to the major
      hemisphere, which makes the minor hemisphere incapable of initiating and
      propagating seizures.

PMID- 15736004
TI  - Stem cells 201: an overview of the ethics of stem cell research.

PMID- 15736006
TI  - Changes in hepatitis C virus (HCV) antibody status in patients with chronic
      hepatitis C after eradication of HCV infection by interferon therapy.
AB  - BACKGROUND: Changes in hepatitis C virus (HCV) antibody status were followed for
      10 years after the eradication of HCV by interferon (IFN) therapy in 30 patients
      with chronic hepatitis C who showed a sustained virological response. METHODS:
      HCV core antibody titer, third-generation HCV recombinant immunoblot assay (RIBA)
      grade (measuring the presence of antibodies for core, NS3, NS4, and NS5
      antigens), and genotype-specific antibodies to the HCV NS4 region were measured
      annually with commercially available kits for these antibodies. RESULTS: For
      grade of HCV antibody determined by RIBA, the most significant decrease was
      observed with anti-NS5 antibody, followed by anti-NS4, anti-NS3, and anti-core
      antibodies, in that order. Tests for anti-NS5 and anti-NS4 antibodies had
      negative results in almost 50% of patients 10 years after eradication of HCV. In
      contrast, the results of tests for anti-core antibody were still markedly
      positive in most patients. However, anti-core antibody titer decreased
      continuously during the 10-year follow-up period. Antibodies to the NS4 region
      specific for HCV genotypes 1 and 2 also decreased during the follow-up period.
      Differences in the rate at which antibody titers decreased were observed between
      antibodies for genotypes 1 and 2; as a consequence, the serological type of HCV
      changed during the follow-up period in some patients. CONCLUSIONS: HCV antibody
      titer appears to continue to decrease during the 10 years after eradication of
      HCV by IFN therapy.

PMID- 15736007
TI  - Interleukin-12 receptor beta 1 chain deficiency in a child with disseminated
      tuberculosis.
AB  - An 11-year-old girl who presented with disseminated tuberculosis associated with
      secondary hemophagocytosis received a diagnosis of interleukin-12 receptor beta 1
      chain deficiency. This diagnosis of immunodeficiency should, therefore, be
      considered for children with disseminated tuberculosis, even in the absence of
      any personal or familial history of prior infection by weakly pathogenic
      Salmonella and Mycobacterium species.

PMID- 15736008
TI  - An outbreak of Phialemonium infective endocarditis linked to intracavernous
      penile injections for the treatment of impotence.
AB  - BACKGROUND: In March 2002, a patient in Tel Aviv, Israel, died of endocarditis
      caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction,
      the patient had been trained to self-inject a compound of vasoactive drugs
      provided by an impotence clinic into his penile corpus cavernosous. METHODS: We
      identified the used prefilled syringes as the source of his infection. Similar
      cases were investigated as a putative outbreak of P. curvatum invasive disease
      among customers of this impotence clinic. P. curvatum isolates, cultured from
      samples obtained from the patients and from prefilled syringes, were compared by
      DNA sequencing of the nuclear ribosomal internal transcribed spacer. RESULTS: We
      identified 2 additional customers at the impotence clinic who had P. curvatum
      endocarditis. In addition, cultures of unused, prefilled syringes and bottles
      provided by the same clinic to 5 asymptomatic customers tested positive for
      pathogenic molds (P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P.
      curvatum isolates were of a single genetic type that is known only from this
      outbreak but is closely related to 3 other P. curvatum genotypes associated with
      pathogenicity in humans. CONCLUSIONS: P. curvatum is an emerging pathogen that
      can be readily isolated from blood. We identified an outbreak of P. curvatum
      endocarditis among men who had erectile dysfunction treated by intracavernous
      penile injections from contaminated prefilled syringes.

PMID- 15736009
TI  - Concurrent sexually transmitted infections (STIs) in sex partners of patients
      with selected STIs: implications for patient-delivered partner therapy.
AB  - BACKGROUND: Patient-delivered partner therapy (PDPT) is the practice of providing
      disease-specific antimicrobial agents to patients for delivery to their sex
      partners. Some partners who receive PDPT may forgo clinical evaluation, resulting
      in missed opportunities for the diagnosis and treatment of comorbid conditions.
      METHODS: We conducted a review of electronic charts for 8623 individuals
      attending 4 sexually transmitted disease clinics who were sex partners of
      patients with selected sexually transmitted infections (STIs). We evaluated the
      concordance between STIs diagnosed in partners and their reported exposures for
      which they might have received PDPT. RESULTS: Among 3503 female and 4647
      heterosexual male partners, 19 (0.4%) of 4716 individuals tested were newly
      diagnosed with human immunodeficiency virus (HIV) infection, and 61 individuals
      (0.7%) had syphilis. Pelvic inflammatory disease was diagnosed in 133 women
      (3.8%). Seventy-two (3.2%) of 2226 female and heterosexual male partners
      reporting exposure to patients with chlamydial infection had gonorrhea diagnosed.
      Chlamydial infection or gonorrhea was diagnosed in 81 heterosexual male partners
      (10.3%) who reported contact with women with trichomoniasis. Among 473 men who
      have sex with men (MSM; including bisexual men), 13 (6.3%) of 207 tested were
      newly diagnosed with HIV infection, and 8 (1.7%) had syphilis. Six (6.1%) of 98
      MSM reporting exposure to patients with chlamydial infection had gonorrhea
      diagnosed. CONCLUSIONS: Infrequent coinfections in female and heterosexual male
      partners exposed to patients with chlamydial infection or gonorrhea would not
      preclude use of PDPT. However, PDPT for male partners of women with
      trichomoniasis and for MSM requires further study.

PMID- 15736010
TI  - Clinical outcomes for hospitalized patients with Legionella pneumonia in the
      antigenuria era: the influence of levofloxacin therapy.
AB  - BACKGROUND: Although the reduction in case-fatality rate recently observed among
      patients with Legionella pneumonia has been largely attributed to the progressive
      utilization of urine antigen testing, other factors, such as changes in empirical
      antibiotic therapy, may also have contributed. We have analyzed more-recent
      outcomes of Legionella pneumonia in an institution where urine antigen testing
      was reflexly performed in cases of community-acquired pneumonia without an
      etiological diagnosis. METHODS: From a prospective series of 1934 consecutive
      cases of community-acquired pneumonia in nonimmunocompromised adults, 139 cases
      of Legionella pneumophila pneumonia were selected for observational review.
      Legionella cases were analyzed for outcome with respect to antibiotic treatment,
      mortality, complications, length of stay, time to defervescence, and stability.
      RESULTS: The early case-fatality rate was 2.9% (4 of 139 patients), and the
      overall case-fatality rate was 5% (7 of 139 patients). One hundred twenty
      patients (86.3%) received an appropriate initial therapy, which included
      macrolides (i.e., erythromycin or clarithromycin) in 80 patients and levofloxacin
      in 40. Levofloxacin progressively replaced macrolides as the initial therapy
      during the study period. Compared with patients who received macrolides, patients
      who received levofloxacin had a faster time to defervescence (2.0 vs. 4.5 days;
      P<.001) and to clinical stability (3 vs. 5 days; P=.002). No differences were
      found regarding the development of complications (25% vs. 25%; P=.906) and case
      fatality rate (2.5% vs. 5%; P=.518). The median length of hospital stay was 8
      days in patients treated with levofloxacin and 10 days in those who received
      macrolides (P=.014). CONCLUSIONS: Legionella pneumonia is still associated with
      significant complications in hospitalized patients, but recent mortality is
      substantially lower than that found in earlier series. Levofloxacin may produce a
      faster clinical response than older macrolides, allowing for shorter hospital
      stay.

PMID- 15736011
TI  - Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus
      macrolides.
AB  - BACKGROUND: The community outbreak of legionnaires disease that occurred in
      Murcia, Spain, in July 2001--to our knowledge, the largest such outbreak ever
      reported--afforded an unusual opportunity to compare the clinical response of
      patients with Legionella pneumonia treated with levofloxacin with that of
      patients treated with macrolides and to determine the role of rifampicin combined
      with levofloxacin in treating severe legionellosis. METHODS: An observational,
      prospective, nonrandomized study was conducted involving 292 patients seen at our
      hospital (Hospital "J. M. Morales Meseguer"; Murcia, Spain) who received a
      diagnosis of Legionella pneumonia during the Murcia outbreak. To compare both
      antibiotic regimens (macrolides vs. levofloxacin), patients were stratified by
      the severity of pneumonia. Duration of fever, clinical outcome, complications,
      side effects, and length of hospital stay were recorded. To assess the potential
      effects of adjuvant therapy with rifampicin, 45 case patients treated with
      levofloxacin plus rifampicin were evaluated and compared with 45 control pairs
      who were treated with levofloxacin alone. RESULTS: With the exception of 2
      patients who died, all patients were cured. There were no significant differences
      between treatment groups in clinical outcome for patients with mild-to-moderate
      pneumonia. Nevertheless, in patients with severe pneumonia, levofloxacin exerted
      superior activity; it was associated with fewer complications (3.4% of patients
      receiving levofloxacin experienced complications, compared with 27.2% of patients
      receiving macrolides; P=.02) and shorter mean hospital stays (5.5 vs. 11.3 days;
      P=.04). Addition of rifampicin to the treatment regimen for patients receiveing
      levofloxacin for severe pneumonia provides no additional benefit. CONCLUSIONS:
      Our findings strongly suggest that monotherapy with levofloxacin is a safe and
      effective treatment for legionnaires disease, including in patients with severe
      disease. In these patients, levofloxacin appears to be more effective than
      clarithromycin.

PMID- 15736012
TI  - Treatment of the common cold with echinacea: a structured review.
AB  - BACKGROUND: Echinacea is a herbal preparation that is frequently used to treat
      the common cold. Spending on echinacea in the United States has risen to >300
      million dollars annually. METHODS: A total of 322 articles related to echinacea
      and colds, including 9 placebo-controlled clinical trials, were identified using
      the Medline and PubMed databases. Eleven features of experimental design that
      affect the accuracy of the measurement of features of interest, the probability
      of a chance relationship, bias, and blinding were used to evaluate the 9 placebo
      controlled studies. The criteria were validated case definition, quantifiable
      hypothesis, sample-size calculation, randomized assignment, double blinding,
      proof of blinding, measurement of compliance, measurement of drop-out rate,
      analysis by intention to treat, description of the methods of analysis, and
      measurement of probability. Equal weight was given to each criterion, since
      failure to meet any one of them could potentially invalidate the findings of a
      clinical trial. RESULTS: Of the 9 studies, 2 met all 11 criteria. The results of
      both studies were judged to be negative by the people who performed the studies.
      Of the remaining 7 studies, 6 were judged to have positive results, and 1 was
      judged to have negative results. The criterion most commonly not met was proof of
      blinding. CONCLUSIONS: This structured review suggests that the possible
      therapeutic effectiveness of echinacea in the treatment of colds has not been
      established.

PMID- 15736013
TI  - Echinacea treatment for the common cold.

PMID- 15736014
TI  - Host-pathogen relationships among Escherichia coli isolates recovered from men
      with febrile urinary tract infection.
AB  - BACKGROUND: Host-pathogen relationships in men with febrile urinary tract
      infection (FUTI) are poorly understood. METHODS: Phylogenetic background,
      extended virulence genotypes, and serotypes were determined for 70 Escherichia
      coli isolates recovered from urine samples obtained from men with FUTI for
      comparison with available data for 70 E. coli rectal isolates recovered from
      uninfected men. Bacterial traits were assessed in relation to underlying host
      characteristics (age, compromise status, and history of urinary tract infection)
      and acute manifestations (bacteremia, flank pain, and serum prostate-specific
      antigen [PSA] level). RESULTS: Compared with rectal isolates, FUTI isolates
      exhibited a significantly higher prevalence of virulence-associated phylogenetic
      groups, serotypes, and extraintestinal virulence genes. The latter included
      traditional prostatitis-associated traits (e.g., hemolysin and cytotoxic
      necrotizing factor), as well as unconventional traits, such as outer membrane
      protease T. These bacterial traits occurred largely independent of host age,
      urological compromise status, urinary tract infection history, and acute
      manifestations. However, certain traits were less prevalent in association with
      use of urinary tract instrumentation and significantly predicted elevated PSA
      levels. CONCLUSIONS: Considerable virulence capability may be required for an E.
      coli strain to cause FUTI in men, regardless of whether most compromising
      conditions are present. Bacterial traits that promote prostatic invasion may be
      relevant for the pathogenesis of FUTI, even among men without classic
      manifestations of acute prostatitis.

PMID- 15736015
TI  - Epidemiology of invasive Haemophilus influenzae type A disease among Navajo and
      White Mountain Apache children, 1988-2003.
AB  - BACKGROUND: Before the introduction of Haemophilus influenzae type b (Hib)
      conjugate vaccines, rates of H. influenzae disease among Navajo and White
      Mountain Apache (WMA) children were among the highest reported worldwide. Routine
      Hib vaccination has significantly reduced rates of Hib disease in these
      populations. As Hib disease rates decrease to very low levels, there are concerns
      that non-type b strains of H. influenzae may emerge as more prevalent causes of
      invasive disease in children. METHODS: We reviewed population-based, active
      laboratory surveillance data from the period of 1988-2003 for invasive H.
      influenzae type a (Hia) disease among Navajo and WMA children aged <5 years.
      Clinical information on cases was collected by chart review. A sample of Hia
      isolates from Navajo children was typed by pulsed-field gel electrophoresis
      (PFGE). RESULTS: During 1988-2003, a total of 76 reported cases of invasive Hia
      disease occurred among Navajo and WMA children. The overall annual incidence was
      20.2 cases per 100,000 population aged <5 years. There was no increase in Hia
      disease rates after Hib vaccination was introduced. The median age of patients
      was 12 months. Meningitis (50% of cases) was the most common presentation,
      followed by pneumonia (27.6%). Two children with Hia disease died. PFGE analysis
      revealed a limited genetic diversity of Hia strains in this population.
      CONCLUSIONS: Active surveillance data showed high rates of invasive Hia disease
      among Navajo and WMA children but no increase in the incidence after Hib
      vaccination was introduced. The presentation of Hia disease is similar to that of
      Hib disease in the prevaccine era.

PMID- 15736016
TI  - Nature abhors vacuum, but public health is loving it: the sustained decrease in
      the rate of invasive Haemophilus influenzae disease.

PMID- 15736017
TI  - Association of hepatitis C virus infection with serum iron status: analysis of
      data from the third National Health and Nutrition Examination Survey.
AB  - BACKGROUND: There is growing evidence that mildly increased amounts of iron in
      the liver can increase hepatic injury, particularly if combined with other
      hepatotoxic factors, such as alcohol use, use of porphyrogenic drugs, or chronic
      viral hepatitis. In the present study, the association of hepatitis C virus (HCV)
      infection with serum measurements of iron status was assessed in the US
      population. METHODS: We analyzed data from a total of 14,462 participants in the
      Third National Health and Nutrition Examination Survey. We excluded subjects who
      were aged <12 years, subjects for whom measurements of serum levels of iron or
      ferritin or the results of liver function tests were missing, and subjects who
      had a serum transferrin saturation of > or =50% (to help exclude subjects with
      hemochromatosis). RESULTS: Mean serum levels of ferritin and iron (+/- standard
      error) were significantly higher among subjects with HCV infection (100+/-3 ng/mL
      and 229+/-17 microg/dL, respectively) than among subjects without liver disease
      (83+/-0.3 ng/mL and 101+/-2.1 microg/dL, respectively) (P<.0001). Serum levels of
      ferritin were directly and significantly correlated with serum levels of alanine
      aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase
      (r=0.25, r=0.24, and r=0.28, respectively; P<.0001), whereas platelet counts were
      inversely correlated with serum levels of ferritin (r=-0.12; P<.0001).
      CONCLUSION: HCV infection is significantly associated with higher serum levels of
      ferritin and iron in the US population.

PMID- 15736018
TI  - Diagnosis and management of central nervous system histoplasmosis.
AB  - Two cases of Histoplasma meningitis are presented, illustrating the difficulty in
      diagnosis and treatment. The first case occurred in a patient with acquired
      immunodeficiency syndrome as a relapse of disseminated histoplasmosis and
      resolved after prolonged treatment and ongoing antiretroviral therapy. The second
      case occurred in a cardiac allograft recipient as meningitis and focal brain
      lesions that responded to liposomal amphotericin B, but the patient died shortly
      after therapy was completed. Unfortunately, there are no prospective studies
      addressing the diagnosis and management of patients with histoplasmosis of the
      central nervous system from which to provide evidence-based guidelines for care.
      In the absence of such data, an approach will be presented on the basis of our
      experience and opinions.

PMID- 15736019
TI  - Serum neopterin, an immune activation marker, independently predicts disease
      progression in advanced HIV-1 infection.
AB  - BACKGROUND: CD4+ T lymphocyte (CD4) counts and plasma human immunodeficiency
      virus (HIV) type 1 RNA concentrations predict clinical outcome in HIV-1
      infection. Our objective was to assess the independent prognostic value for
      disease progression of soluble markers of immune system activation. METHODS: This
      retrospective marker-validation study utilized previously obtained clinical and
      laboratory data, including CD4+ cell counts, and made use of stored frozen serum
      samples to assay for levels of beta2-microglobulin, neopterin, endogenous
      interferon, triglycerides, interleukin-6, soluble tumor necrosis factor- alpha
      receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse-transcriptase
      inhibitor resistance. The 152 patients who participated in this study represented
      a subsample of participants in AIDS Clinical Trials Group (ACTG) 116B/117, a
      randomized trial that demonstrated the clinical benefit of didanosine over
      zidovudine monotherapy in persons with advanced HIV-1 infection. Marker data were
      analyzed in relation to protocol-defined clinical disease progression, using Cox
      proportional hazards models. RESULTS: The median duration of follow-up was 344
      days. Elevated baseline values for neopterin (P=.0009), endogenous interferon
      (P=.00039) and interleukin-6 (P=.0007) were each associated with greater
      subsequent risk of clinical disease progression. In a head-to-head comparison
      that was adjusted for CD4+ cell count (P=.0165) and HIV-1 RNA level (P=.1220), we
      found that elevated values for neopterin (P=.0002) and, to a lesser extent,
      endogenous interferon (P=.0053) were the strongest predictors of increased risk
      of clinical disease progression 6 months later. CONCLUSIONS: Soluble markers of
      immune activation add prognostic information to CD4 counts and viral load for
      risk of disease progression in advanced HIV-1 infection. The robust performance
      of neopterin, an inexpensive and reliably measured serum marker, supports its
      potential suitability for patient monitoring, particularly in resource-limited
      settings.

PMID- 15736020
TI  - Hepatitis C virus coinfection and HIV load, CD4+ cell percentage, and clinical
      progression to AIDS or death among HIV-infected women: Women and Infants
      Transmission Study.
AB  - BACKGROUND: Despite previous study, it remains unclear whether hepatitis C virus
      (HCV) coinfection affects the progression of human immunodeficiency virus (HIV)
      type 1 infection. The Women and Infants Transmission Study provided an
      opportunity to assess this issue. METHODS: Longitudinal data on 652 HIV-1
      infected women enrolled in the study before the availability of highly active
      antiretroviral therapy (HAART; 1989-1995) were analyzed. Random effects models
      were used to determine whether HCV coinfection was associated with different CD4+
      cell percentages and HIV-1 RNA levels over time, and Cox proportional hazards
      models were used to compare the rates of clinical progression to acquired
      immunodeficiency syndrome (AIDS) or death. RESULTS: Of 652 women, 190 (29%) were
      HCV infected. During follow-up, 19% of women were exposed to HAART. After
      controlling for indicators of disease progression (CD4+ cell percentages and HIV
      1 RNA levels determined closest to the time of delivery in pregnant women),
      ongoing drug use, receipt of antiretroviral therapy, and other important
      covariates, no differences were detected in the HIV-1 RNA levels, but the CD4+
      cell percentages were slightly higher in HCV-infected women than in HCV
      uninfected women. During follow-up, 48 women had progression to a first clinical
      AIDS-defining illness (ADI), and 26 died with no documented antecedent ADI. In
      multivariable analyses, HCV-infected participants did not have faster progression
      to a first class C AIDS-defining event or death (relative hazard, 0.75; 95%
      confidence interval, 0.37-1.53). CONCLUSIONS: In this cohort, the rate of
      clinical progression of HIV-1 infection was not greater for HCV-infected women.

PMID- 15736022
TI  - Incomplete antibody evolution and seroreversion after treatment of primary HIV
      type 1 infection: what is the clinical significance?

PMID- 15736021
TI  - Incomplete HIV type 1 antibody evolution and seroreversion in acutely infected
      individuals treated with early antiretroviral therapy.
AB  - BACKGROUND: The diagnosis of human immunodeficiency virus type 1 (HIV-1)
      infection by standard tests relies on the formation of HIV-1-specific antibodies.
      Early treatment of acute HIV-1 infection may have unique immunologic effects on
      host cellular and humoral responses. Rare cases of HIV-1 seroreversion have been
      reported for patients with advanced or rapidly progressive disease. Here, we
      report seroreversion that occurred in subjects with acute HIV-1 infection who
      initiated early antiretroviral therapy. METHODS: A total of 150 patients with
      symptomatic acute or early onset HIV-1 infection that was treated with
      antiretroviral therapy were observed prospectively by means of monthly clinical
      and laboratory evaluation, which included serial HIV enzyme-linked immunosorbent
      assay and Western blots, until a fully evolved HIV-1 antibody response was
      documented. RESULTS: Three patients who initiated antiretroviral therapy a mean
      interval of 8 days (range, 1-16 days) after presentation and were observed for a
      mean duration of 50.2 months (range, 40.2-55.7 months) did not develop a fully
      evolved HIV-1 antibody response or demonstrated complete or partial HIV-1
      seroreversion, despite maintenance of cytomegalovirus-specific humoral responses.
      Virologic suppression and seroreversion (complete or partial) occurred a mean
      duration of 4.1 months (range, 2.3-5.7 months) and 15.5 months (range, 6.7-26.3
      months), respectively, after the initiation of therapy. All patients maintained
      complete virologic suppression while receiving therapy and had an undetectable
      HIV-1 RNA load at the time of seroreversion. CONCLUSIONS: Early antiretroviral
      therapy associated with durable virologic suppression in acute HIV-1 infection
      may abrogate the formation or detection of HIV-1-specific antibodies. Ongoing
      antigenic stimulation may be required to maintain HIV-1-specific humoral
      responses. Incomplete evolution of the HIV-1 antibody response and/or presence of
      seroreversion (although infrequently observed) underscore the potential unique
      immunologic effect of early antiretroviral therapy in patients with primary HIV-1
      infection.

PMID- 15736023
TI  - No observed effect of GB virus C coinfection on disease progression in a cohort
      of African woman infected with HIV-1 or HIV-2.
AB  - We studied mortality among subjects with human immunodeficiency virus (HIV)-1 and
      HIV-2 infection in relation to GB virus (GBV)-C coinfection. No significant
      differences in mortality were seen between subjects with and subjects without GBV
      C coinfection who also had either HIV-1 or HIV-2 infection. No association
      between GBV-C and HIV plasma virus loads or CD4 cell count was observed.

PMID- 15736024
TI  - High incidence of the Beijing genotype among multidrug-resistant isolates of
      Mycobacterium tuberculosis in a tertiary care center in Mumbai, India.
AB  - We report a high frequency (35%) of the Beijing genotype among multidrug
      resistant isolates recovered in and around Mumbai, India. Further restriction
      fragment-length polymorphism typing showed that these strains were closely
      related. We also report a high frequency of the Delhi genotype (31% of isolates).
      Our data indicate considerable ongoing transmission of multidrug-resistant
      Mycobacterium tuberculosis strains of the Beijing genotype in Mumbai.

PMID- 15736025
TI  - Severe meningoencephalitis caused by human herpesvirus 6 type B in an
      immunocompetent woman treated with ganciclovir.
AB  - Human herpesvirus 6 (HHV-6), the causative agent of exanthema subitum in
      childhood, can also induce meningoencephalitis in immunocompromised individuals.
      In contrast, HHV-6 encephalitis in immunocompetent patients is rare, and the
      clinical syndrome not well defined. We report a case of meningoencephalitis
      caused by HHV-6 type B in an otherwise healthy woman.

PMID- 15736026
TI  - Evidence of human herpesvirus 6 infection in 4 immunocompetent patients with
      encephalitis.
AB  - We describe 4 patients with encephalitis due to possible reactivation of human
      herpesvirus 6 (HHV-6) infection who were enrolled in the California Encephalitis
      Project. All were immunocompetent and had HHV-6 loads determined in cerebrospinal
      fluid specimens. Tests for detection of HHV-6 should be considered for
      individuals with encephalitis.

PMID- 15736027
TI  - Human herpesvirus 6 infection of the central nervous system: is it just a case of
      mistaken association?

PMID- 15736028
TI  - Who are you--Staphylococcus saprophyticus?
AB  - Staphylococcus saprophyticus is a leading cause of cystitis in young women. S.
      saprophyticus shares many clinical features of urinary tract infection caused by
      Escherichia coli, but differs in pathogenesis, seasonal variation, and geographic
      distribution. This review summarizes what is known and what still needs to be
      learned about this microorganism.

PMID- 15736029
TI  - Epidemiology of nasopharyngeal carriage of Neisseria meningitidis in healthy
      Dutch children.
AB  - We investigated the prevalence and determinants of nasopharyngeal carriage of
      Neisseria meningitidis in 3200 healthy children aged 1-19 years. The incidence of
      meningococcal carriage was, on average, 1.5%. Peak incidences were seen at age 1
      year and after age 15 years. The independent determinants of meningococcal
      carriage included age, regular visits to youth clubs (odds ratio [OR], 2.2) and
      discotheques (OR, 4.3), and pneumococcal carriage (OR, 4.1).

PMID- 15736030
TI  - Decreased erythromycin use after antimicrobial reimbursement restriction for
      undocumented bacterial upper respiratory tract infections significantly reduced
      erythromycin resistance in Streptococcus pyogenes in Taiwan.

PMID- 15736031
TI  - Pathogenic mechanisms of mitochondrial DNA depletion in patients with HIV-1
      infection.

PMID- 15736032
TI  - Is the recent emergence of community-associated methicillin-resistant
      Staphylococcus aureus among participants in competitive sports limited to
      participants?

PMID- 15736033
TI  - Treatment of brain abscess caused by Listeria monocytogenes in a patient with
      allergy to penicillin and trimethoprim-sulfamethoxazole.

PMID- 15736034
TI  - Nosocomial outbreak of hepatitis E infection in Pakistan with possible parenteral
      transmission.

PMID- 15736035
TI  - Abacavir pharmacokinetics in hepatic dysfunction.

PMID- 15736036
TI  - Morphological aspects of potassium flow in the semicircular canal ampulla of the
      pigeon.
AB  - Potassium ions are a prerequisite for the development and regulation of sensory
      cell stimulation in the inner ear. From the potassium-rich endolymph the ions
      flow into the sensory cells apically and are released basolaterally. After
      transport pathways of various lengths potassium is released again into the
      endolymph - in the cochlea by marginal cells of the stria vascularis, in the
      vestibular labyrinth by dark cells. While this long recycling pathway is
      relatively well-known in the cochlea, few studies have been conducted on the
      semicircular canal ampullae (SCCA) where its morphological basis is largely
      unknown. According to the present electron microscopic findings, potassium ions
      are initially released into the extracellular space during stimulation of the
      sensory cells and then absorbed by supporting and light cells. Finally they are
      transported transcellularly over numerous very long gap junctions into the region
      of the dark cells. From here they move to an extracellular compartment, which is
      more or less completely sealed off basally by basal plates of the light cells.
      Apically the intercellular space between light and dark cells is sealed by
      junctional complexes. This newly identified space in the SCCA corresponds to the
      extracellular compartment between the marginal and intermediate cells in the
      stria vascularis. At both sites, the cochlea and the SCCA, this probably serves
      as a regulatory valve, reservoir or storage space, particularly for potassium
      ions. It is likely that the different morphology of the ion transport pathways is
      related to the different flow levels of potassium ions expressed by the different
      levels of the so-called endocochlear potential and concomitant movement of other
      ions in the cochlea and SCCA.

PMID- 15736037
TI  - Histological heterogeneity of human glioblastomas investigated with an
      unsupervised neural network (SOM).
AB  - The histological variability of Glioblastomas (GB) precludes the modern
      assimilation of theses tumors into a single histological tumor group. As an
      alternative to statistical histological evaluation, we investigated 1489 human GB
      in order to discover whether they could be correctly classified using Self
      Organizing Maps (SOM). In all tumors 50 histological features, as well as the age
      and sex of the patients, were examined. Four clusters of GB with a significance
      of 52 (maximal significance 60) were found. Cluster C1 contained 37.47% of all GB
      and 41.09% of all polymorphic glioblastomas (PG). Cluster C2 included 35.06% of
      all GB and 44.96% of all giant cell glioblastomas (GCG). Cluster C3 contained
      16.45% of all GB with a significant component of astroblasts, glioblasts and
      oligodendroglia. Cluster C4 included 11.01% of all GB, 87.80% of the gliosarcomas
      (GS) and 36.72% of all GCG. Placing a series of component windows with their maps
      side by side allows the immediate recognition of the dependencies on variables
      and the determination of variables necessary to build the specific clusters. The
      SOM allow a realistic histological classification, comparable to the actual
      classification by the WHO. In addition, we found new, small subclusters of human
      GB which may have a clinical significance. With SOM one can learn to
      discriminate, discard and delete data, select histological and clinical or
      genetic variables that are meaningful, and consequently influence the result of
      patient management.

PMID- 15736038
TI  - Streptidine, a metabolic derivative produced after administration of streptomycin
      in vivo, is vestibulotoxic in rats.
AB  - Streptomycin is the treatment of choice in developing countries for patients
      suffering from tuberculosis or other infectious diseases. However, it produces
      incapacitating vestibular symptoms whose onset is delayed and gradual. This
      observation led to the notion that a streptomycin metabolic derivative and not
      the antibiotic itself is the damaging agent for the inner ear. To study further
      the existence of this ototoxic metabolite, chronic treatment with streptomycin or
      its putative derivative streptidine was carried out in young male Long Evans
      rats. The presence of streptomycin or streptidine in the blood of animals of
      either experimental group was assessed by high performance liquid chromatography
      and analysis of swimming behavior was used to evaluate vestibular damage.
      Features of the sensory epithelium and quantification of hair cells were attained
      in sections of the utricular organ of all groups by light microscopy. After 25,
      35 and 45 days of treatment with streptomycin, a metabolite with the same
      chromatographic properties as the streptidine standard run in parallel was
      identified in the blood of rats. Concentrations of the metabolite were 2.26
      microg/ml on the 25th day and around 8.0 microg/ml in both the 35th and the 45th
      day of treatment, while streptomycin was below its detection level at either
      period. In streptidine-treated rats, the concentration of this compound was 1.0,
      1.84 and 4.94 microg/ml on the 25th, 35th and 45th treatment days, respectively.
      Treatment with either streptomycin or streptidine resulted in similar abnormal
      swimming patterns and histological alterations of the utricular epithelium. Loss
      of hair cells was roughly equivalent even though streptidine was administered in
      a dose 90% lower than streptomycin. The gradual appearance of streptidine as a
      metabolic derivative of the antibiotic in the blood of rats or the administration
      of this compound alone, causing similar functional and structural vestibular
      deterioration seen in streptomycin-treated animals, supports the notion that
      streptidine is a potential contributor to ototoxicity after prolonged antibiotic
      administration.

PMID- 15736039
TI  - Expression pattern of cell cycle-related gene products in synovial stroma and
      synovial lining in active and quiescent stages of rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the expression pattern of cell cycle related gene
      products in active and quiescent Rheumatoid arthritis (RA). METHODS: Synovial
      tissue from 20 patients with active proliferative RA and 28 patients with RA in
      remission was immunohistochemically examined for expression of p53, p63, p21,
      p27, p16, cyclin D1, CDK4, RB, E2F, Ki-67 on tissue microarrays and by DNA flow
      cytometry for cell cycle phases. RESULTS: Elevated expression of p53 and p27 was
      found in synovial lining and in stromal cells in proliferative active RA. In the
      remission stage this finding was confined to the synovial lining. Most of the
      cells were in the G0-phase. Ki-67 proliferation index was maximum 10% in synovial
      cells. CONCLUSION: The p53 pathway is activated in synovial cells in active RA as
      well as in quiescent stage of disease. Differences in the spatial expression
      pattern of proteins involved in the p53 pathway in RA in remission compared to
      actively proliferating RA reflect the phasic nature of the disease and support in
      our opinion the concept of adaptive role of p53 pathway in RA.

PMID- 15736040
TI  - Histopathological changes in the eyes in systemic lupus erythematosus: an
      electron microscope and immunohistochemical study.
AB  - This paper reports the histopathological findings in the eyes of a 26-year-old
      female patient diagnosed with systemic lupus erythematosus (SLE) with peripheral
      neuropathy. The patient had no significant ocular problems. She died of pneumonia
      after two years of suffering. The eyeballs were procured at autopsy and the
      retina, choroid and optic nerve processed for light and electron microscopy, and
      immunohistochemistry for immunoglobulin G (IgG), glial fibrillary acidic protein
      (GFAP), calbindin and parvalbumin. Histologically, there was haemorrhaging in the
      retinal nerve fibre layer. Ultrastructurally, the axons of this layer were
      swollen, and contained an unusual accumulation of microtubules and smooth
      endoplasmic reticulum. There were degenerative changes in the pericytes and
      smooth muscle cells of blood vessels. The capillary lumen was partially
      obliterated, and contained IgG, which was also detected throughout the choroid
      and wall of choroidal arterioles. The latter and Bruch's membrane showed fibrin
      deposits. The optic nerve showed infiltrated mononuclear cells near the
      degenerated axons, these axons lacked immunoreactivity to calbindin and
      parvalbumin. Compared to the control, the connective tissue sheaths of the
      central retinal vessels possessed a vast number of proliferated fibroblast cells,
      and trichrome staining showed transmural vessel scarring. Dense GFAP
      immunoreactivity was observed surrounding the vessel wall. These pathological
      changes are due to impaired blood circulation caused by haemorrhaging and
      vasculitis, and vessel occlusion by fibrin. The nature of the changes observed
      tends to indicate that a regular, thorough ophthalmic examination should be
      conducted even in the absence of significant ocular symptoms in SLE.

PMID- 15736041
TI  - Immunocytochemical developmental patterns of the thoracolumbar sympathetic chain
      in the chick and a comparison with its adrenal counterpart.
AB  - The immunocytochemical development of the thoracolumbar sympathetic ganglion and
      its adrenal counterpart was studied in the chick from days 3.5 to 12 of
      incubation, using antibodies to 17 separate antigens, including antibodies to pan
      neuroendocrine markers, catecholamine-synthesizing and proprotein-processing
      enzymes, and neuropeptides. Some of the antigens studied (Go protein-alpha
      subunit, thyrosine hydroxylase, and galanin) were strongly expressed from the
      first days of development, whereas others (chromogranin-A, chromogranin-B, 7B2
      protein, and somatostatin) showed a diverse immunoreactive expression at
      different stages. Three different patterns were found in the development of both
      adrenal medulla and thoracolumbar sympathetic ganglion. In the first
      (chromogranin-A and B, Go protein-alpha subunit, tyrosine hydroxylase, HNK-1, and
      galanin), virtually all medullary and thoracolumbar sympathetic ganglion cells
      were strongly immunostained from day 4 onward. Except for HNK-1, chromogranin-A
      and B, there was a steady increase in immunoreactive cells for all the remaining
      antigens up to day 12. In the second (7B2 protein, proprotein convertase 2, and
      secretogranin II), full antigenic expression was reached in medullary and
      thoracolumbar sympathetic ganglion cells by day 10. In the third pattern
      (proprotein convertase 3, somatostatin, dopamine-beta-hydroxylase, neuron
      specific enolase, vasoactive intestinal polypeptide, and met-enkephalin),
      differences in immunoreactivity were observed between the medullary and
      thoracolumbar sympathetic ganglion cells.

PMID- 15736042
TI  - NPY and TH innervation in human choroidal whole-mounts.
AB  - To determine the distribution of NPY and TH human choroidal innervation,
      choroidal whole-mounts were processed for indirect immunofluorescence. An
      antibody to a component of the neuronal cytoskeleton, neurofilament 200 kDa (NF
      200) was used to identify neurons and axons. A double immunostaining was
      performed, antibodies against NF-200 being combined with antibodies against
      neuropeptide Y (NPY) and tyroxine hydroxylase (TH). Fibers containing both NPY
      and TH were distributed in three plexuses, one in the suprachoroid large-sized
      vessel layer, and two in the medium-sized vessel layer. Intrinsic choroidal
      neurons (ICNs) containing NPY and TH were observed in the suprachoroid. The TH(+)
      ICNs were located in the medium-sized vessel layer. Overall, NPY(+) and TH(+)
      ICNs were more frequent in the central temporal area, both in isolation and
      forming microganglia. We also detected small spindle elements intensely
      immunoreactive to TH(+) and distributed mainly in the suprachoroid from the
      equator to the periphery. In conclusion, the human choroid contains abundant NPY
      and TH nerve fibers related to chroroidal vascular structures; it further
      possesses NPY(+) and TH(+) ICNs which contribute to the choroidal self-regulation
      persisting after sympathetic denervation. Additionally, these ICNs may at least
      partially explain why the choroidal blood flow does not respond to the factors
      that influence systemic vascular control. The preferential location of these
      cells in the submacular area suggests that dysfunction or degeneration of these
      cells may be a factor in vascular pathologies found in ocular disease, such as
      diabetic macular edema or age-related macular degeneration.

PMID- 15736043
TI  - Local immune response in serous papillary carcinoma of the endometrium.
AB  - OBJECTIVE: Serous papillary carcinomas of the endometrium are aggressive tumors
      that tend to permeate, in a very extensive fashion, to uterine and adnexal
      lymphatic and vascular channels at an early stage in their evolution, and are
      associated with a particularly gloomy prognosis. It is generally thought that
      even tumors apparently limited to the endometrium or confined to an endometrial
      polyp have a poor outcome. Our study points towards the value of HLA-DR antigen
      in the outcome of serous papillary endometrial cancer. Our aim was to assess the
      HLA-DR expression in inactive, endometrial intraepithelial carcinoma (EIC), and
      invasive serous carcinoma curretage specimens from the endometrial cavity,
      suggesting a role in immune response to keep tumor proliferation in check. STUDY
      DESIGN: Thirty-one cases of inactive endometrium, twelve cases of EIC, and thirty
      nine cases of serous papillary invasive carcinoma curettings were evaluated for
      the detection of HLA-DR monoclonal antigen. T helper (TH) marker (CD4) in the
      tumor stroma of the relevant cases was also studied, given that it is now known
      that the dependence of immune responsiveness on the class II antigens reflects
      the central role of these molecules in presenting antigen to TH cells. RESULTS:
      HLA-DR was expressed in 20 of 31 inactive endometrium (64.5%), 4 of 12 in EIC
      (33.3%), and in 10 of 39 serous papillary invasive carcinomas (25.6%). CD4 was
      expressed in 9 of 31 inactive endometrium (29%), 5 of 12 in EIC (42%), and in 26
      of 39 serous papillary invasive carcinomas (67%). CONCLUSIONS: The results showed
      decreased expression of HLA-DR and increased expression of CD4 as the lesion
      progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells
      of inactive endometrium, of EIC and of serous papillary invasive carcinomas
      agrees with the hypothesis of the inactive endometrium - carcinoma in situ
      sequence as the usual route for the development of serous papillary invasive
      carcinoma. The immune attract mechanism by low HLA-DR signaling seems to be of
      minor importance in the malignant and metastatic potential of the serous
      papillary endometrial tumours.

PMID- 15736044
TI  - Characterization of metaplastic and heterotopic epithelia in the human
      gastrointestinal tract by the expression pattern of acyl-CoA synthetase 5.
AB  - Metaplastic and heterotopic epithelia are frequently found in the human
      intestine. The recently cloned human acyl-CoA synthetase 5 (ACS5) is a key enzyme
      in providing cytosolic acyl-CoA thioesters. The aim of the study was to identify
      and to locate the expression of ACS5 in the gastric body and the small intestine
      with metaplasia or heterotopia by different methods. In the normal
      gastrointestinal tract, ACS5 was predominantly found in the villus epithelium of
      the small intestine, but not in the gastric mucosa. Of note, strong expression of
      ACS5 was also detectable in intestinal metaplasia of the stomach. Inversely, ACS5
      expression could neither be detected in heterotopic gastric mucosa of the corpus
      type nor in gastric, pseudopyloric, or antral metaplasia of the small intestine.
      In conclusion, our data implicate that ACS5 is a suitable differentiating marker
      molecule in the gastrointestinal tract.

PMID- 15736045
TI  - Differential expression of tissue kallikrein in the skin of systemic sclerosis.
AB  - Systemic sclerosis (SSc) is characterised by ischemic damage, impaired
      angiogenesis and skin fibrosis. Tissue kallikrein (t-kallikrein) is involved
      through kinins in inflammation, vasorelaxation and angiogenesis. T-kallikrein is
      synthetised by endothelial, smooth muscle, and inflammatory cells and, in skin,
      also by dark cells of the sweat glands, where it is involved in sweat formation.
      Our aim was to analyse, by immunohistochemistry and RT-PCR, the expression of t
      kallikrein in the skin of patients with different SSc subsets, limited (lSSc) and
      diffuse (dSSc), and phases, early and advanced. Skin biopsies were taken from 18
      SSc patients and 10 controls. Immunohistochemistry was performed on paraffin
      sections with an antibody against human urinary t-kallikrein. For RT-PCR, cDNA
      from skin biopsies was amplified using primers specific for human t-kallikrein.
      In the control skin, dark cells of the secretory units of sweat glands showed
      immunopositivity for t-kallikrein as well as blood vessels. In the lSSc skin,
      immunoreactivity was observed only in some glands, with weak staining in the
      advanced phase. In early lSSc skin, immunoreactivity was observed in microvessel
      walls and in the inflammatory infiltrate. In dSSc skin, dark cells of the
      glandular fundus units, and the few remaining vessels showed scarcity (early
      phase) or lack (advanced phase) of immunoreactivity for t-kallikrein. RT-PCR
      confirmed a decrease of t-kallikrein mRNA levels from early to advanced phase in
      SSc subsets, reaching its lowest level in advanced dSSc. In conclusion,
      immunohistochemical and biomolecular results indicate that t-kallikrein is
      decreased in the skin of SSc patients and decreases progressively from the early
      to advanced phase of lSSc and dSSc. The decreased expression of t-kallikrein may
      be involved in the impairment of the sweating process, vessel functionality and
      angiogenesis.

PMID- 15736046
TI  - Corneal endothelial cell density decreases with age in emmetropic eyes.
AB  - PURPOSE: To analyze the corneal endothelial cell density in healthy adult
      emmetropic subjects. METHODS: We analyzed the corneal endothelial cell density of
      a group made up of 225 emmetropic subjects (n=225). As age-matched control groups
      we analyzed two other groups, one made up of myopic subjects (n=209) and the
      other made up of hyperopic subjects (n=203). We recorded the mean of three
      consecutive measurements of the corneal endothelial cell density using the Topcon
      SP-2000P non-contact specular microscope (Topcon Corp., Tokyo, Japan). RESULTS:
      The mean age was 38.6+/-11.8 years, 40.7+/-12.2 years, and 39.2+/-10.5 years for
      emmetropic, myopic and hyperopic subjects respectively (p=0.994). No significant
      differences (p=0.920) in endothelial cell density values were found between
      emmetropic (2985+/-245 cells/mm2), myopic (2936+/-258 cells/mm2) and hyperopic
      eyes (2946+/-253 cells/mm2). Lower corneal endothelial cell density values were
      found in older emmetropic (p<0.001), myopic (p<0.001), and hyperopic subjects
      (p<0.001). A significant correlation between endothelial cell density and age was
      found in emmetropic (r=-0.958; p<0.001), myopic (r= -0.954; p<0.001) and
      hyperopic subjects (r= -0.948; p<0.001). CONCLUSIONS: In healthy emmetropic
      subjects there is a reduction in corneal endothelial cell density with age
      although there are no differences in corneal endothelial cell density values
      between emmetropic, myopic and hyperopic subjects.

PMID- 15736047
TI  - Immunodetection of aldose reductase in normal and diseased human liver.
AB  - Aldose reductase is an NADPH-dependent aldo-keto reductase best known as the rate
      limiting enzyme of the polyol pathway that is implicated in the complications of
      diabetes. Aldose reductase appears to be involved in a variety of disease states
      other than diabetes, presumably due to its ability to catalyze the reduction of a
      broad spectrum of aldehydes, including some cytotoxic products of lipid
      peroxidation. Although the data regarding expression of aldose reductase in
      normal liver are conflicting, prior studies have suggested that the enzyme may be
      induced in diseased liver. The goal of these studies was to characterize
      expression of aldose reductase in normal and diseased human liver, using RT-PCR,
      Western analysis and immunohistochemistry. Aldose reductase transcripts and
      protein were detected at low levels in control human livers. In contrast, levels
      of aldose reductase mRNA and protein were increased in chronically diseased human
      livers. Immunohistochemistry demonstrated localization of aldose reductase in
      sinusoidal lining cells; dual immunofluorescence confocal microscopy with the
      macrophage marker, CD68, confirmed that the aldose reductase-positive sinusoidal
      lining cells were Kupffer cells. Abundant aldose reductase-positive, CD68
      positive cells were present in the fibrous septa of cirrhotic livers, accounting
      for the increase in immunoreactive aldose reductase in diseased livers.
      Immunostaining of human lung, spleen and lymph node revealed that macrophages in
      those tissues also express aldose reductase. These data are the first to
      demonstrate that aldose reductase is expressed by human macrophages in various
      tissues and suggest that this enzyme may play a role in immune or inflammatory
      processes.

PMID- 15736048
TI  - Administration of L-arginine reduces the delay of the healing process caused by
      ibuprofen. Implication of COX and growth factors expression.
AB  - The objective of the present study has been to advance knowledge of the gastric
      role played by the amino acid L-Arginine (L-Arg) in the evolution of a chronic
      gastric ulcer. In order to clarify it, L-Arg alone or together with Ibuprofen
      have been administrated in an experimental acetic acid chronic ulcer, analysing
      characteristic parameters of an active curative process, such as PGE2 production,
      COX expression, and also angiogenesis, proliferation/apoptosis and growth factors
      expression. Our results reveal that L-Arg is favourable in the healing process
      improving the curative course. Ibuprofen caused a delay in ulcer healing, more
      evident 14 days after ulcer induction; COX-2 expression was increased at the 7th
      day although no signal of protein could be detected after 14 days; PGE2
      production was inhibited in intact and ulcerated areas at both times assayed. In
      contrast, treatment with L-Arg reduced the delay of the lesion, the increment in
      COX-2 expression induced by Ibuprofen, and was able to maintain PGE2 levels
      similar to the control group after 14 days. Additionally, the histological study
      showed that the healing effects of L-Arg might be associated with an increased
      angiogenesis and FGF-2 expression. These actions could be considered key factors
      in the healing response associated with L-Arg administration. However, the
      proliferation study assayed with the PCNA-immunostaining method did not reveal
      significant differences, as the same as the apoptosis analysis. In conclusion,
      the coupling of L-Arg to Ibuprofen is an attractive alternative to Ibuprofen
      administration alone because it not only attenuates but also improves the
      evolution of chronic lesions through mechanisms that implicate endogenous PG and
      FGF-2-associated pathways, which allow an increase of angiogenesis process.

PMID- 15736049
TI  - A simple method for the differential characterization of alveoli and alveolar
      ducts in injured lungs.
AB  - RATIONALE AND HYPOTHESIS: Previous studies evaluating the histoarchitecture of
      distal airspaces have been shown to be limited by the difficulty in adequately
      differentiating alveoli and alveolar ducts. This limitation has been specially
      noticed in studies addressing lung recruitment and in situations of diffuse
      alveolar damage (DAD), where generic nominations for distal airspaces had to be
      created, such as "peripheral airspaces" (PAS) and "large-volume gas-exchanging
      airspaces" (LVGEA). Elastic stains have been largely used to describe normal lung
      structures. Weigert's resorcin-fuchsin staining (WRF) demarcates the thickened
      free portions of the ductal septum facilitating its recognition. We hypothesized
      that this staining could help in differentiating alveoli from alveolar ducts in
      distorted lung parenchyma. MATERIAL AND METHODS: Samples of control lungs and of
      DAD lungs induced by mechanical ventilation (VILI) were stained with hematoxylin
      eosin (HE) and with WRF. Using morphometry we assessed the volume proportion of
      alveoli, alveolar ducts and LVGEA in control and VILI lungs. RESULTS: WRF stained
      VILI lungs showed a significant decrease in the volume proportion of LVGEA and
      alveoli and a significant increase in the volume proportion of alveolar ducts
      when compared to HE stained samples. CONCLUSION: We conclude that WRF staining is
      useful to distinguish alveolar ducts from alveoli in a DAD model, and suggest
      that it should be routinely used when morphometric studies of lung parenchyma are
      performed.

PMID- 15736050
TI  - Microtubules regulate aortic endothelial cell actin microfilament reorganization
      in intact and repairing monolayers.
AB  - To understand the role of microtubules and microfilaments in regulating
      endothelial monolayer integrity and repair, and since microtubules and
      microfilaments show some co-alignment in endothelial cells, we tested the
      hypothesis that microtubules organize microfilament distribution. Disruption of
      microtubules with colchicine in resting confluent aortic endothelial monolayers
      resulted in disruption of microfilament distribution with a loss of dense
      peripheral bands, an increase in actin microfilament bundles, and an associated
      increase of focal adhesion proteins at the periphery of the cells. However, when
      microfilaments were disrupted with cytochalasin B, microtubule distribution did
      not change. During the early stages of wound repair of aortic endothelial
      monolayers, microtubules and microfilaments undergo a sequential series of
      changes in distribution prior to cell migration. They are initially distributed
      randomly relative to the wound edge, then align parallel to the wound edge and
      then elongate perpendicular to the wound edge. When microtubules in wounded
      cultures were disrupted, dense peripheral bands and lamellipodia formation were
      lost with increases in central stress fibers. However, following microfilament
      disruption, microtubule redistribution was not disrupted and the microtubules
      elongated perpendicular to the wound edge similar to non-treated cultures.
      Microtubules may organize independently of microfilaments while microfilaments
      require microtubules to maintain normal organization in confluent and repairing
      aortic endothelial monolayers.

PMID- 15736051
TI  - Irradiation of the rabbit cornea with UVB rays stimulates the expression of
      nitric oxide synthases-generated nitric oxide and the formation of cytotoxic
      nitrogen-related oxidants.
AB  - Until now, the role of nitric oxide (NO) in cornea irradiated with UVB rays
      remains unknown. Therefore, we investigated nitric oxide synthase isomers (NOS),
      enzymes that generate NO, nitrotyrosine (NT), a cytotoxic byproduct of NO, and
      malondialdehyde (MDA), a byproduct of lipid peroxidation, in rabbit corneas
      repeatedly irradiated with UVB rays (312 nm, 1x daily for 6 days, the dose per
      day 1.01 J/cm2) using immunohistochemical methods. The biochemical measurement of
      nitrite and nitrate has been used for the indirect investigation of NO
      concentration in the aqueous humor. Results show that in contrast to normal
      corneas, where of the NOS isomers only endothelial nitric oxide synthase (NOS3)
      was expressed in a significant amount (in the epithelium and endothelium), in
      irradiated corneas all NOS isomers (also brain nitric oxide synthase, NOS1, and
      inducible nitric oxide synthase, NOS2) as well as an indirect measure of ONOO
      formation and MDA were gradually expressed, first in the epithelium, the
      endothelium and the keratocytes beneath the epithelium and finally in the cells
      of all corneal layers and the inflammatory cells that invaded the corneal stroma.
      This was accompanied by an elevated concentration of NO in the aqueous humor. In
      conclusion, repeated irradiation with UVB rays evoked the stimulation of NO
      production, peroxynitrite formation (demonstrated by NT residues) and lipid
      peroxidation (evaluated by MDA staining).

PMID- 15736052
TI  - Biochemical analysis and immunohistochemical determination of cardiac troponin
      for the postmortem diagnosis of myocardial damage.
AB  - Cardiac disease is the most common cause of sudden death in Western nations. In
      forensic practice there is a need for more sensitive diagnostic methods for the
      postmortem diagnosis of myocardial damage. The aim of this study was to analyse
      the diagnostic efficacy of biochemical markers in cadaver fluids in conjunction
      with histological studies and the immunohistochemical determination of cardiac
      troponin C (cTnC) and cardiac troponin T (cTnT) levels in myocardial tissue fixed
      in formol and included in paraffin. We studied 50 cadavers (43 males and 7
      females) with a mean age of 47.5 years (SD 19.2; range 12 to 87 years). Cases
      were chosen according to the postmortem interval, cause of death, and
      circumstances of death. Pericardial fluid and serum were tested in duplicate for
      cardiac troponin I (cTn I), myoglobin and CKMB by immunoassay system using
      commercial kits. In myocardial tissue, histological studies were performed with
      hematoxylin and eosin (HE), Masson's trichrome staining and immunohistochemical
      techniques involving streptavidin-biotin-peroxidase were performed. The results
      pointed to statistically significant differences for all the biochemical markers
      in pericardial fluid. The highest levels were obtained in the group of cadavers
      who had died from myocardial infarction. The immunohistochemical expression of
      cTnC was detected in 86% of cases; it was strongly positive and usually diffuse.
      The expression of cTnT, was much less frequent (46% of cases) and less intense.
      It was concluded that the immunohistochemical determination of cTnC and cTnT
      levels in myocardial tissue may be used as an index of myocardium damage.

PMID- 15736053
TI  - Dose-dependent promoting effect of dextran sodium sulfate on mouse colon
      carcinogenesis initiated with azoxymethane.
AB  - We previously reported a powerful tumor-promoting ability of dextran sodium
      sulfate (DSS) in a novel mouse model for colitis-related colon carcinogenesis
      initiated with azoxymethane (AOM). To determine the dose-dependent influence of
      DSS in our animal model, male ICR mice were given a single intraperitoneal
      injection of AOM (10 mg/kg body weight), followed by DSS at dose levels of 2, 1,
      0.5, 0.25, and 0.1% (w/v) in drinking water for 1 week. All animals were
      sacrificed at week 14 and histological alterations in their colon and
      nitrotyrosine immunohistochemistry were examined to evaluate the nitrosative
      stress. In the mice which received AOM and 2% DSS, the incidences (multiplicity)
      of colonic tubular adenoma and adenocarcinoma were 75% (1.25+/-1.26/mouse) and
      100% (2.75+/-2.22/mouse), respectively. Mice given AOM and 1% DSS had 80%
      incidence of adenoma (1.00+/-0.71/mouse) and 60% incidence of adenocarcinoma
      (1.40+/-2.07/mouse) in the colon. In a mouse treated with AOM and 0.5% DSS, only
      one colonic adenoma (20% incidence with 0.20+/-0.45 multiplicity) developed.
      Higher frequency of high-grade colonic dysplasia was noted in mice given AOM and
      2% or 1% DSS when compared with mice treated with AOM and lower doses of DSS.
      Also, scoring of inflammation and nitrotyrosine immunoreactivity suggested that
      severe inflammation and nitrosation stress caused by high-doses (2% and 1%) of
      DSS contribute its tumor-promoting effects in mouse colon carcinogenesis
      initiated with a low dose of AOM. Thus, our findings indicate that a tumor
      promoting effect of DSS was dose-dependent (1% or more) and the effect might
      occur under the condition of inflammation and nitrosation stress.

PMID- 15736054
TI  - Impairment of thrombospondin-1 expression during epithelial wound healing in
      corneas of vitamin A-deficient mice.
AB  - The purpose of this study is to investigate the expression of thrombospondin-1
      (TSP-1), a multifunctional extracellular matrix protein, during re
      epithelialization in wounded corneas of vitamin A-deficient mice. Epithelial
      defects were created in the corneas of normal and Vitamin A-deficient mice with a
      microgrinder. Wounded corneas were stained with fluorescein and photographed for
      evaluation of re-epithelialization. Histological examination and
      immunohistochemical analysis of TSP-1 expression were also performed on the
      specimens from wounded corneas. In vitamin A-deficient mice, re-epithelialization
      of the wounded corneal epithelium was significantly delayed compared with that in
      normal mice. TSP-1 was detectable neither in the unwounded corneal epithelium of
      normal mice nor in that of vitamin A-deficient mice. In normal mice, linear
      staining of TSP-1 was observed on the wounded corneal surface and stroma at 30
      min and 8 h to 16 h, respectively, after abrasion, and this TSP-1 expression
      disappeared at 36 to 48 h, when re-epithelialization was completed. In contrast,
      no TSP-1 staining was observed in the wounded corneas of vitamin A-deficient
      mice, except for the endothelial cells, throughout the wound healing process.
      Histological examination revealed a progressive increase in polymorphonuclear
      neutrophil infiltration in the stroma of the corneas of vitamin A-deficient mice
      during the healing process. These findings suggest that vitamin A may modulate
      the expression of TSP-1 in the corneas to accelerate the re-epithelialization of
      wounded corneas.

PMID- 15736055
TI  - Expression of Skp2 and p27KIP1 in naevi and malignant melanoma of the skin and
      its relation to clinical outcome.
AB  - Skp2 (S-phase kinase associated protein 2) controls progression from G- to S
      phase by promoting the proteolysis of the cyclin dependent kinase inhibitor
      p27KIP1. Despite the fact that a p27KIP1 decrease has been documented in melanoma
      progression, the role of Skp2 in these tumours is unknown. We therefore examined
      by immunohistochemistry the expression of Skp2, p27KIP1 and Ki-67 in 10 naevi
      (Ns), 15 superficial spreading melanomas (SSMs), 10 nodular melanomas (NMs) and
      14 melanoma metastases (Ms). Nuclear Skp2 expression augmented with increasing
      malignancy (Ns: 1.4%, SSMs: 5.6%, NMs: 17.3%, Ms: 19.1%). In all tumours nuclear
      Skp2 expression correlated with Ki-67 (p=0.024) and inversely with p27KIP1
      (p=0.007). A cytoplasmic reaction for Skp2 was also observed in most tumours and
      its expression decreased from Ns (12.3%) to SSMs (7.9%) and NMs (4.5%). In
      contrast, Ms showed an increase of cytoplasmic Skp2 (11.9%) that correlated with
      its nuclear expression (p=0.016). While nuclear Skp2 expression correlated with
      the pT-level (p=0.023), Clark-level (p=0.023) and Breslow index (p=0.019), the
      cytoplasmic Skp2 expression might be of biological significance only in NMs since
      it correlated with tumour depth (p=0.02) and pT-level (p=0.025). Our data
      suggests that Skp2 could contribute to melanoma progression. This is further
      highlighted by the fact that vertical growth phase (VGP) melanomas show
      significant higher nuclear Skp2 expressions when compared with the harmless
      radial growth phase (RGP) (p=0.047). Also nuclear Skp2 expression correlates with
      a reduced survival time (p=0.025) in melanoma.

PMID- 15736056
TI  - Response of the gut neuroendocrine system of Leuciscus cephalus (L.) to the
      presence of Pomphorhynchus laevis Muller, 1776 (Acanthocephala).
AB  - Immunohistochemical tests were applied to sections of intestine of uninfected and
      Pomphorhynchus laevis Muller-infected chub, Leuciscus cephalus (L.) using 15
      different antisera. Nerve cell bodies and fibres immunoreactive (IR) to the anti
      bombesin, -Cholecystokinin-8 (CCK-8), -galanin, -Gastrin-Releasing Peptide (
      GRP), -Nitric Oxide Synthase (-NOS), -Substance P (-SP), and -Vasoactive
      Intestinal Peptide (-VIP) sera were observed in the myenteric plexus of
      uninfected chub. The density of nerve components immunoreactive to these antisera
      was high in the intestine of the infected fish, especially near the site of
      attachment. Moreover, numerous nerve fibres, immunoreactive to anti-bombesin, 
      GRP, -galanin, -SP, and -VIP sera, were encountered in the connective tissue
      capsule surrounding the bulb and proboscis of P. laevis. The occurrence of P.
      laevis in the chub gut significantly increased the number of endocrine cells per
      intestinal fold immunoreactive to galanin, met-enkephalin and leu-enkephalin
      antisera. CCK-8, Neuropeptide Y and glucagon-like immunoreactive cells were less
      numerous in the intestine of infected chub. A large number of cells in the tunica
      propria-submucosa of L. cephalus infected with P. laevis were immunoreactive to
      anti-serotonin and -leu-enkephalin sera.

PMID- 15736057
TI  - X-irradiation reduces lesion scarring at the contusion site of adult rat spinal
      cord.
AB  - Spinal cord injury (SCI) results in cell death and tissue destruction, and
      ultimately cavitation followed by the formation of lesion scars at the injury
      site. The lesion scars include an astrocytic component (glial scar) and a
      fibroblastic component (connective tissue scar). The purpose of the present study
      is to determine if X-irradiation could minimize the formation of lesion scars and
      reduce the levels of chondroitin sulfate proteoglycans (CSPGs) in the contusion
      SCI model of the adult rat. Two weeks after SCI, a connective tissue scar formed
      at the injury site consisting primarily of fibroblasts and exhibits strong CSPG
      immunoreactivity. The fibroblasts might originate from the connective tissue of
      pia mater or arachnoid mater. At the same time, reactive astrocytes in the spared
      tissue accumulate surrounding the lesion cavity to form a thick glial scar with
      significant enhancement of glial fibrillary acidic protein (GFAP) and CSPG
      immunoreactivity. After X-irradiation (40 Gy) of the injury site 2 days post
      injury, that results in an attenuated dose to the lesion, the connective tissue
      scar was not observed, and accordingly, almost no CSPG immunoreactivity was
      detected at this area. Meanwhile, the glial scar and its CSPG immunoreactivity
      were prominently reduced. X-irradiation did not show significant improvement in
      locomotor recovery, but resulted in a slight delay of body weight recovery
      following injury. This preparative treatment could be used to reduce secondary
      scarring in the lesion resulting in an enriched site for further treatment such
      as growth related transplantation.

PMID- 15736058
TI  - Immunohistochemical localization of phosphatidylcholine in rat mandibular
      condylar surface and lower joint cavity by cryotechniques.
AB  - The immunolocalization of phospholipids has not yet been clearly demonstrated in
      temporomandibular joints (TMJs). We have examined the distribution of one of
      phospholipids, phosphatidyl-choline (PC), in the rat mandibular condylar surface
      and lower joint cavity. Some fresh resected TMJs with their disks attached were
      immediately plunged into isopentane-propane cryogen (-193 degrees C). Cryostat
      sections were cut, mounted on NH3+-coated slides, and fixed with paraformaldehyde
      (PF). Cryosections were first immunostained with anti-mouse PC antibody (JE-1).
      Subsequently, they were labeled with immunogold particles following silver
      enhancing for light microscopic analyses. Some cryosections were subjected to
      double immunofluoresecence labeling with anti-fibronectin antibody or hyaluronic
      acid-binding protein in combination with the anti-PC antibody. As an
      immunocontrol, other cryosections were pretreated with phospholipase A2 before
      such immunofluorescence labeling. We have confirmed the presence of PC in the
      lower joint cavity of rat TMJs as well as on the mandibular condylar surface
      layer, which was colocalized with hyaluronic acid and fibronectin respectively.
      However, by treatment with phospholipase A2, such immunolabeling for PC was
      clearly decreased, showing that the PC is a component in the rat in vivo TMJ.
      These findings suggest that PC, hyaluronic acid and fibronectin may interact each
      other in the TMJ articular surface areas to play a functional role for
      lubrication in TMJ.

PMID- 15736059
TI  - Effects of single, double or triple combinations of octreotide, galanin and
      serotonin on a human pancreatic cancer cell line.
AB  - The human pancreatic cancer cell line (SW 1990) was exposed to 0.2 microg/ml of
      octreotide, galanin or serotonin as single, double or triple combinations. The
      tumor cells were checked at 3, 6 and 12 hours. In order to determine the number
      of viable cancer cells, the MTT-assay was used. Proliferation, apoptosis and the
      expression of epidermal growth factor were detected with immunohistochemistry
      using the avidin-biotin complex method. In addition, apoptosis was also detected
      with (TUNEL) method. The primary antibodies used were proliferating cell nuclear
      antigen (PCNA), anti-poly (ADP-ribose) polymerase (PARP) and anti-human epidermal
      growth factor. Single treatment with octreotide or serotonin reduced, the number
      of viable cells and the proliferation index at all observation times. Galanin
      increased the number of viable cells and the proliferation index. Whereas double
      treatments containing octreotide reduced the number of viable cells, those
      containing galanin increased the number. The effect of single, double or triple
      treatment on the apoptotic index obtained with both TUNEL method and PARP
      expression varied depending on the combination and the observation time.
      Octreotide did not affect the tumor cell expression of EGF. Galanin and
      serotonin, on the other hand, increased the expression of EGF. Whereas triple
      combination increased the expression of EGF after 6 h, all the other double
      combinations decreased this expression. It has been concluded that treatment with
      a combination of octreotide and serotonin may be useful in clinical settings.

PMID- 15736060
TI  - Smad4 expression in gastric adenoma and adenocarcinoma: frequent loss of
      expression in diffuse type of gastric adenocarcinoma.
AB  - Smads are signal transducers for the members of the TGF-beta superfamily. Of
      these Smads, Smad4 is essential for TGF-beta signaling. The purpose of this study
      was to elucidate Smad4 expression and localization in 65 gastric adenomas, 49
      intestinal-type and 39 diffuse type of gastric adenocarcinomas (including 12
      cases of fresh frozen tissue) using Real-time RT-PCR and immunohistochemistry.
      Real-time RT-PCR showed that intestinal type gastric adenocarcinomas have higher
      Smad4 mRNA expression than diffuse type gastric adenocarcinomas.
      Immunohistochemical stain for Smad4 revealed that expression of Smad4 was
      significantly lower in diffuse-type gastric adenocarcinoma than intestinal-type
      gastric adenocarcinomas. Also, higher Smad4 protein expression in intestinal type
      gastric adenocarcinomas than overall gastric adenoma was noted. The rate of
      reduced Smad4 expression was higher in advanced gastric cancer than early gastric
      cancer. These results suggest that Smad4 might play different roles in human
      gastric carcinogenesis, especially between intestinal type and diffuse type of
      gastric adenocarcinoma.

PMID- 15736062
TI  - Human and animal spongiform encephalopathies are the result of chronic autoimmune
      attack in the CNS: a novel medical theory supported by overwhelming experimental
      evidence.
AB  - Spongiform encephalopathies, also called "prion diseases", are fatal degenerative
      diseases of the central nervous system which can occur in animals (such as the
      "mad cow disease" in cattle) and also in humans. This paper presents a novel
      medical theory concerning the pathogenic mechanisms for various human and animal
      spongiform encephalopathies. It is hypothesized that various forms of prion
      diseases are essentially autoimmune diseases, resulting from chronic autoimmune
      attack of the central nervous system. A key step in the pathogenic process
      leading towards the development of spongiform encephalopathies involves the
      production of specific autoimmune antibodies against the disease-causing prion
      protein (PrPsc) and possibly other immunogenic macromolecules present in the
      brain. As precisely explained in this paper, the autoimmune antibodies produced
      against PrPsc are responsible for the conversion of the normal cellular prion
      protein (PrPc) to PrPsc, for the accumulation of PrPsc in the brain and other
      peripheral tissues, and also for the initiation of an antibody-mediated chronic
      autoimmune attack of the central nervous system neurons, which would contribute
      to the development of characteristic pathological changes and clinical symptoms
      associated with spongiform encephalopathies. The validity and correctness of the
      proposed theory is supported by an overwhelming body of experimental observations
      that are scattered in the biomedical literature. In addition, the theory also
      offers practical new strategies for early diagnosis, treatment, and prevention of
      various human and animal prion diseases.

PMID- 15736061
TI  - Photopigment coexpression in mammals: comparative and developmental aspects.
AB  - In mammals, each cone had been thought to contain only one single type of
      photopigment. It was not until the early 1990s that photopigment coexpression was
      reported. In the house mouse, the distribution of color cones shows a
      characteristic division. Whereas in the upper retinal field the ratio of short
      wave to middle-to-long wave cones falls in the usual range (1:10), in the ventral
      retinal field M/L-pigment expression is completely missing. In the transitional
      zone, numerous dual cones are detectable (spatial coexpression). In other species
      without retinal division, dual cones appear during development, suggesting that
      M/L-cones develop from S-cones. Dual elements represent a transitory stage in M/L
      cone differentiation that disappear with maturation (transitory coexpression).
      These two phenomena seem to be mutually exclusive in the species studied so far.
      In the comparative part of this report the retinal cone distribution of eight
      rodent species is reported. In two species dual cones appear in adult specimens
      without retinal division, and dual elements either occupy the dorsal peripheral
      retina, or make up the entire cone population. This is the first observation
      proving that all cones of a retina are of dual nature. These species are good
      models for the study of molecular control of opsin expression and renders them
      suitable sources of dual cones for investigations on the role and neural
      connections of this peculiar cone type. In the developmental part, the retinal
      maturation of other species is examined to test the hypothesis of transitory
      coexpression. In these species S-pigment expression precedes that of the M/L
      pigment, but dual cones are either identified in a small number or they are
      completely missing from the developing retina. These results exclude a common
      mechanism for M/L-cone maturation: they either transdifferentiate from S-cones or
      develop independently.

PMID- 15736063
TI  - The signaling network of tumor invasion.
AB  - The ability of a cell to invade its surroundings is an important hallmark of
      malignant tumors and results from aberrant cell signaling mechanisms. The signal
      transduction that leads to tumor invasion can be broken down into major pathways.
      Even though the pathway systems are distinct in themselves, none of these
      pathways operate independently when it comes to transmitting signals that
      culminate in an invasive phenotype. That is, the malignant change in one receptor
      not only leads to malignant changes directly downstream but can also affect the
      molecules of many other pathways. Three major pathway systems involved in tumor
      invasion are discussed in this review: the integrin system, the insulin-like
      growth factor system, and the Rho family GTPases. Here we see that although the
      individual signaling systems can each contribute to invasion, each system is
      networked to others and should not be considered isolated. Each system is first
      reviewed as independent contributors to an invasive phenotype and then discussed
      in the context of interacting pathways that collectively result in tumor
      invasion.

PMID- 15736064
TI  - Bioactive lysophospholipids and mesangial cell intracellular signaling pathways:
      role in the pathobiology of kidney disease.
AB  - Lysophosphatidic acid (LPA), lyso-phosphatidylcholine (LPC), and sphingosine-1
      phosphate (S1P) are major biologically active lysophospholipids (LPLs) that are
      produced by activated platelets, monocyte/macrophages, and many types of
      mammalian cells. LPLs have been shown to induce a wide array of physiological and
      pathophysiological properties including cellular differentiation, proliferation,
      migration, extracellular matrix deposition, change in morphology, and chemotactic
      responses. The recent cloning and identification of G protein-coupled receptors
      as specific receptors for LPLs created a great deal of interest in LPLs signaling
      and diverse biological responses. The pathobiological role of LPLs has been
      implicated in a number of pathological states and human diseases including
      atherosclerosis, glomerulosclerosis, post-ischemic renal failure, polycystic
      kidney disease, and ovarian cancer. Although the research in this area is growing
      at an enormous rate, this review is specifically focused on the recent
      understanding of the pathophysiological properties of LPA and LPC with special
      reference to kidney diseases, and their specific G-protein-coupled receptors and
      intracellular signaling pathways.

PMID- 15736065
TI  - Functional aspects of the somatostatinergic system in the retina and the
      potential therapeutic role of somatostatin in retinal disease.
AB  - The somatostatinergic system of the retina has been investigated in a variety of
      studies. A considerable amount of experimental evidence is available concerning
      the patterns of expression of somatostatin (SRIF) and its receptors in vertebrate
      retinas. However the functional roles of this peptidergic system in retinal
      physiology are far from being elucidated. Nonetheless, data have been provided
      concerning the regulatory action of SRIF on the excitability of different retinal
      cell types and on the modulation of ion channels in different vertebrate retinas.
      The present review is focused on recent and unpublished investigations of the
      mouse retina relative to the involvement of specific SRIF receptors in the
      regulation of ion channels and transmitter release, the transduction pathways
      coupled to SRIF receptors, and the mechanisms regulating the expression of SRIF
      and its receptors as derived from studies in transgenic animal models. In these
      models, altered expression levels of SRIF or of specific SRIF receptors have also
      been found to affect the morphology of retinal cell types (namely the rod bipolar
      cells) and to result in functional alterations at the level of both ion channel
      regulation and transmitter release. These new pieces of evidence constitute an
      important step forward in the understanding of the functional actions of the
      retinal somatostatinergic system, although our current knowledge is far from
      being exhaustive. The ultimate goal of understanding SRIF functional actions in
      the retina is concerned with the possibility of using SRIF or its analogs as
      therapeutic agents to cure retinal diseases. Indeed, encouraging results are
      being obtained in clinical investigations focused on the use of SRIF analogs to
      treat diabetic retinopathy, a retinal disease with high social impact and
      originating as a complication of diabetes. The closing part of the present paper
      examines the evidence supporting SRIF as a promising therapeutic agent in this
      disease.

PMID- 15736066
TI  - Standardization of bone marrow features--does it work in hematopathology for
      histological discrimination of different disease patterns?
AB  - Standardized bone marrow (BM) features determined by semiquantitative scoring are
      valuable tools for the recognition and easily reproducible interpretation of
      histological patterns in hematopathology. This procedure may help to characterize
      various disease entities, but especially to differentiate chronic
      myeloproliferative disorders (MPDs) with increased platelet counts from reactive
      thrombocytosis (RTh). A clear-cut separation of these conditions continues to
      present a major problem in hematology. Therefore MPDs are a most suitable model
      to test the diagnostic relevance of this procedure. By regarding the literature
      and based on archive material that involved BM biopsies of 319 patients, a
      semiquantitative grading of histological parameters was performed. Standardized
      features were applied for a stepwise discriminant analysis to establish different
      sets of variables exerting a diagnostic impact. A distinction into five
      histological patterns was achieved that showed a correctly predicted group
      membership of about 94 %. These were consistent with the clinicopathological
      diagnosis of polycythemia vera, essential thrombocythemia (ET), prefibrotic or
      early fibrotic chronic idiopathic myelofibrosis (CIMF) and finally RTh. Variables
      of discriminating potency according to their ranking included megakaryopoiesis
      (maturation defects, nuclear lobulation, naked and bulbous nuclei, small and
      giant size), reticulin fibers, erythro- and granulopoiesis (left shifting and
      quantity) and cellularity. These findings are in keeping with the assumption that
      characteristic patterns of BM histopathology can be assigned to different
      subtypes of MDPs mimicking ET. Discrimination between ET and especially early
      stage CIMF with thrombocythemia is warranted because of significant implications
      concerning therapeutic strategies, follow-up examinations and survival. Regarding
      these results, a schematic procedure is proposed to be used for daily routine
      diagnosis concerning the discrimination of MPDs.

PMID- 15736067
TI  - The tumor suppressor RASSF1A in human carcinogenesis: an update.
AB  - Loss of heterozygosity of the small arm of chromosome 3 is one of the most common
      alterations in human cancer. Most notably, a segment in 3p21.3 is frequently lost
      in lung cancer and several other carcinomas. We and others have identified a
      novel Ras effector at this segment, which was termed Ras Association Domain
      family 1 (RASSF1A) gene. RASSF1 consists of two main variants (RASSF1A and
      RASSF1C), which are transcribed from distinct CpG island promoters. Aberrant
      methylation of the RASSF1A promoter region is one of the most frequent epigenetic
      inactivation events detected in human cancer and leads to silencing of RASSF1A.
      Hypermethylation of RASSF1A was commonly observed in primary tumors including
      lung, breast, pancreas, kidney, liver, cervix, nasopharyngeal, prostate, thyroid
      and other cancers. Moreover, RASSF1A methylation was frequently detected in body
      fluids including blood, urine, nipple aspirates, sputum and bronchial alveolar
      lavages. Inactivation of RASSF1A was associated with an advanced tumor stage
      (e.g. bladder, brain, prostate, gastric tumors) and poor prognosis (e.g. lung,
      sarcoma and breast cancer). Detection of aberrant RASSF1A methylation may serve
      as a diagnostic and prognostic marker. The functional analyses of RASSF1A reveal
      an involvement in apoptotic signaling, microtubule stabilization and mitotic
      progression. The tumor suppressor RASSF1A may act as a negative Ras effector
      inhibiting cell growth and inducing cell death. Thus, RASSF1A may represent an
      epigenetically inactivated bona fide tumor suppressor in human carcinogenesis.

PMID- 15736068
TI  - Nestin structure and predicted function in cellular cytoskeletal organisation.
AB  - Nestin is an intermediate filament protein expressed in dividing cells during the
      early stages of development in the CNS, PNS and in myogenic and other tissues.
      Upon differentiation, nestin becomes downregulated and is replaced by tissue
      specific intermediate filament proteins. Interestingly, nestin expression is
      reinduced in the adult during pathological situations, such as the formation of
      the glial scar after CNS injury and during regeneration of injured muscle tissue.
      Although it is utilised as a marker of proliferating and migrating cells very
      little is known about its functions or regulation. In depth studies on the
      distribution and expression of nestin in mitotically active cells indicate a
      complex role in regulation of the assembly and disassembly of intermediate
      filaments which together with other structural proteins, participate in
      remodeling of the cell. The role of nestin in dynamic cells, particularly
      structural organisation of the cell, appears strictly regulated by
      phosphorylation, especially its integration into heterogeneous intermediate
      filaments together with vimentin or alpha-internexin.

PMID- 15736070
TI  - [Cytoarchitectural structure of the areas of language].
AB  - INTRODUCTION AND DEVELOPMENT: There is a correlation between the higher brain
      functions and the degree of development of the associated cortices, but their
      efficiency depends on the patterns of cytoarchitectural organisation. Specialised
      areas can be distinguished in the neocortex and in the thalamus. Portions of the
      pars opercularis and triangularis of the inferior frontal gyrus (Broca's area)
      together with the posterior temporal region (Wernicke's area) are essential for
      the production and understanding of human speech, these being more developed in
      the left hemisphere of humans. The frontal lobe in front of Brodmann's areas
      numbers 6 and 8 represents a late phylogenetic acquisition, which is only
      developed in primates and in humans, that acts to sustain highly discriminating
      activities linked to the planning, execution and control of tasks that require
      the selection of programmes and flexibility for them to be applied. In its
      anterolateral sector, the temporal lobe has areas that are only shared with
      primates (such as area 20) or which are exclusive to humans (area 38), and which
      are important when it comes to assessing the vital significance of intellectually
      captured events. CONCLUSIONS: The three fundamental features of the human
      cerebral cortex are considerable folding, stratification and pillarisation, and
      its scant thickness. The rationale behind this work was to present the complex
      and sophisticated biological substrate for the development of speech and language
      in human beings and the connections within the temporal lobe and outside them, as
      well as the bi-hemispheric competence needed to enable the higher tutoring
      processes.

PMID- 15736071
TI  - [Functional neuroanatomical correlations of the perisylvian area in autism
      spectrum disorders].
AB  - INTRODUCTION: Autism spectrum disorders cover a continuum of disorders ranging
      from severe autism to mild autism and Asperger's syndrome. They are considered to
      be a subgroup of the pervasive development disorders and are characterised by the
      alteration of three basic areas of behaviour, qualitative alterations in
      reciprocal social interaction, qualitative alterations in communication and
      patterns of behaviour, and stereotyped, repetitive and restrictive activities and
      interests. These alterations are expressed to a greater or lesser degree
      depending on the level of severity of the disorder and can be detected and
      quantified by clinical instruments such as the ADI-R (Autism Diagnostic Interview
      Revised) and the CARS (Childhood Autism Rating Scale). AIMS. Our aim was to
      establish a relationship between the specific behavioural characteristics of
      autism (evaluated by ADI-R and CARS) and brain structures and functions. PATIENTS
      AND METHODS: The sample was made up of 10 subjects (9 boys and 1 girl) diagnosed
      with pervasive development disorder. RESULTS: We obtained statistically
      significant Spearman correlations between the ADI-R item restricted, repetitive
      and stereotyped behaviour patterns and the area of the right inferior precentral
      gyrus. A positive correlation was also found between the item for abnormality or
      apparent deviation in development before the age of 36 months and the right
      supramarginal gyrus area, while the correlation was negative between the former
      and the left postcentral gyrus. There was also a significant correlation between
      the number of perisylvian areas and epileptiform activity and qualitative
      incapacity in communication on the ADI-R, and some items on the CARS with areas
      of the perisylvian zone. CONCLUSIONS: Our findings confirm the relation between
      functional alterations of the different areas that make up the perisylvian region
      and the distinct behavioural features that define and characterise autism.

PMID- 15736072
TI  - [The prevalence of attention deficit hyperactivity disorder].
AB  - INTRODUCTION: Hyperactivity is a common, genetically-based disorder in childhood
      in which a number of neurological and psychological factors that give rise to
      attentional disorders, impulsiveness and motor overactivity are involved.
      DEVELOPMENT: The prevalence rate of attention deficit hyperactivity disorder
      (ADHD) is a controversial matter. Although the DSM-IV gives an interval of
      between 3 and 5%, which is probably the value that is most widely accepted by the
      scientific community, there is in fact a very high degree of variability.
      According to different authors, an interval of 2-30% is obtained in the general
      population. In Anglo-Saxon countries the most commonly accepted prevalence of
      this entity is 5%, but few studies have been conducted in our country. In an
      epidemiological study with a community-based sample extracted by multistage,
      stratified sampling in school-age children on the island of Majorca, the
      estimated prevalence of ADHD was 4.7%. The authors consider aspects concerning
      the prevalence of ADHD and subtypes by ages, sex, in both the clinical and
      community environments. CONCLUSIONS: The analysis of these data will enable us to
      compare the different evaluation methods used and to draw conclusions about
      screening and early detection methods.

PMID- 15736073
TI  - [Specific language disorders: their diagnosis, classification and study using
      magnetoencephalography].
AB  - INTRODUCTION: Specific language disorder (SLD) is defined as a disorder in which
      language is slow and retarded with respect to the patient's chronological age,
      and which is not related to a sensory-auditory or motor deficit or to a pervasive
      development disorder; in other words, structural and functional neurological
      developmental disorders must be excluded. After many studies and attempts to
      reach an agreement, specific language disorders have been broadly classified into
      two groups: specific expressive language disorder and specific receptive
      expressive language disorder. AIMS: Our objective was to study SLD using
      magnetoencephalography (MEG) in order to look for epileptiform manifestations in
      precise language areas. PATIENTS AND METHODS: We studied a sample made up of 11
      patients with SLD, one of whom had Landau-Kleffner syndrome and one with
      cryptogenic-type SLD. The criteria used were age-dependent autism exclusion tests
      and specific language tests for SLD. The MSI technique was carried out on all the
      patients, by magnetic resonance and MEG. RESULTS: A characteristic pattern is
      obtained for SLD in the form of irregular spike and polyspike-wave discharges in
      bilateral frontal channels. The dipoles were situated mainly in the left
      perisylvian areas. CONCLUSIONS: The study of specific language disorders using
      MEG enables us to identify the SLD included in a proposed classification as
      primary-type specific language disorder, cryptogenic-type specific language
      disorder and secondary-type type specific language disorder, like Landau-Kleffner
      syndrome.

PMID- 15736074
TI  - [Verbal dyspraxia: its clinical characteristics and treatment with speech
      therapy].
AB  - INTRODUCTION: Verbal dyspraxia is a specific developmental language disorder that
      is characterised by a deficit at different levels of speech processing: in
      phonological planning, in phonetic planning and in the implementation of the
      speech motor programme. DEVELOPMENT: In this study we review the criteria for
      differential diagnosis, the tests that are useful to achieve this and the
      possible lines of speech therapy treatment.

PMID- 15736075
TI  - [Speech therapy intervention in comprehension disorders].
AB  - INTRODUCTION: Most of the studies conducted on the subject of language
      pathologies have focused on the expressive aspect, but there is now generalised
      agreement on considering that most language disorders stem essentially from
      problems in the processes allowing input of verbal information provided by the
      environment. DEVELOPMENT: We analyse the processes that take place in a child's
      mind when faced with verbal production and the communicative intentions of
      others, in an attempt to understand the nature of their difficulties.
      CONCLUSIONS: The comprehension of oral language brings into play a series of
      extremely complex processes that combine different domains of higher mental
      functioning. Speech therapy intervention must ensure it analyses the true extent
      of the verbal comprehension of each child and attempt to achieve a representation
      of the levels of alteration involved in the faulty understanding.

PMID- 15736076
TI  - [Can we cure autism? From outcome to intervention].
AB  - Outcome in autism is variable but with a significant trend toward a poor
      prognosis and despite reports that outcome in individuals with autism may be
      improving secondary to early intensive interventions there is still much to be
      learned about the natural history and the effects of intervention in autism
      spectrum disorders. While there may not be a known cure for autism, there are a
      number of viable treatment options available. The primary models of treatment are
      non pharmacological interventions that include intervention models such as
      applied behavior analysis and developmental and structured teaching. The role of
      pharmacological interventions is limited to treating specific symptoms that may
      be interfering with a child's ability to learn or function within a particular
      environment. The question of whether or not we can cure autism needs to be
      discussed in terms of the need to overcome the as of yet poorly understood
      fundamental disturbance in autism and the need to develop treatment protocols
      specifically targeting social deficits. At the present time, it is more
      appropriate to speak of our quest to understand autism than it is to speak of a
      cure.

PMID- 15736077
TI  - [The social deficit in autism: focus on joint attention].
AB  - INTRODUCTION AND DEVELOPMENT: Autism is best thought of as a spectrum disorder
      with the dimensional components of social cognition, communication and
      flexibility varying between individuals meeting the criteria of autism. The core
      clinical feature that defines autism is a disturbance in social interaction which
      is not absolute and differs depending on a child's cognitive level, developmental
      stage, and the type of social structure in which they are observed. Social skills
      are under strong genetic influence with a continuous distribution of social
      interaction deficits in the general population with arbitrary cutoffs defining
      who is and is not affected with an autism spectrum disorder; this is the result
      of a complex interplay between numerous biological and environmental factors.
      Joint attention refers to the capacity of individuals to coordinate attention
      with a social partner in relation to some object or event and a disturbance in
      this early skill and in particular impairment in the ability to initiate joint
      attention, is a central symptom of autism. CONCLUSIONS: There are data to suggest
      that dorso-medial frontal cortex and anterior cingulate contribute to the
      development of an infant's ability to maintain representations of self, a social
      partner and an interesting object. The ability to engage frequently in social
      orienting behaviors and ultimately in numerous episodes of social attention
      coordination, or joint attention, may be a critical experience during a
      particular developmental window that serves to organize social neurodevelopment.
      A neurodevelopmental model explaining how these early deficits in social
      cognition may lead to autism is reviewed.

PMID- 15736078
TI  - [Syndromic autism: I. General aspects].
AB  - INTRODUCTION AND DEVELOPMENT: The diagnosis of autism is based on the
      identification of certain behavioural criteria, but there is no biological test
      that allows us to diagnose the disorder. Yet, a considerable number of cases of
      autism, estimated to be somewhere between 11 and 37%, are linked to specific
      syndromes that can be identified according to their clinical characteristics, or
      by means of some biological marker. These cases are known as syndromic autism or
      'double syndromes'. There is a relation between autism and certain genetic and
      metabolic diseases, epilepsy, infections of the nervous system, intrauterine
      exposure to certain substances and perinatal pathologies. CONCLUSIONS: The aim of
      this review is to guide the professional in the diagnosis of autistic children in
      order to rationalise the process by ruling out any underlying disease or syndrome
      related to the autistic condition. At the same time, we stress aetiological
      aspects of these syndromes, which make it easier to understand the biological
      bases of autism.

PMID- 15736079
TI  - [Syndromic autism: II. Genetic syndromes associated with autism].
AB  - INTRODUCTION AND DEVELOPMENT: In this study we report on the different genetic
      syndromes in which autism has been described as one of the possible
      manifestations. CONCLUSIONS: Certain genetic syndromes are providing us with
      extremely valuable information about the role played by genetics in autism. This
      is the case of the following syndromes: Angelman syndrome, Prader-Willi syndrome,
      15q11-q13 duplication, fragile X syndrome, fragile X premutation, deletion of
      chromosome 2q, XYY syndrome, Smith-Lemli-Opitz syndrome, Apert syndrome,
      mutations in the ARX gene, De Lange syndrome, Smith-Magenis syndrome, Williams
      syndrome, Rett syndrome, Noonan syndrome, Down syndrome, velo-cardio-facial
      syndrome, myotonic dystrophy, Steinert disease, tuberous sclerosis, Duchenne's
      disease, Timothy syndrome, 10p terminal deletion, Cowden syndrome, 45,X/46,XY
      mosaicism, Myhre syndrome, Sotos syndrome, Cohen syndrome, Goldenhar syndrome,
      Joubert syndrome, Lujan-Fryns syndrome, Moebius syndrome, hypomelanosis of Ito,
      neurofibromatosis type 1, CHARGE syndrome and HEADD syndrome.

PMID- 15736080
TI  - [Cognitive evoked potentials in face recognition in autism].
AB  - INTRODUCTION AND DEVELOPMENT: Face recognition requires a special type of
      processing that is different to that used to recognise objects. The right medial
      region of the fusiform gyrus displays a higher degree of activation when dealing
      with faces, which is why it is known as the fusiform face area, although the
      integrity of the right occipital face area may be needed to perform this task.
      Neuroimaging studies point not only to the existence of normal activation of the
      fusiform face area in response to faces but also of the occipital area. One
      modulation that supports the existence of a specific pathway is the face
      inversion effect, which is defined as the process in which greater disability is
      displayed in the recognition of inverted faces than for other mono-oriented
      objects. The P1 potential is the initial endogenic component of visual
      processing, acting as an index of the processing of features that show lower
      latency and greater amplitude when dealing with a face stimulus than when
      stimulated by objects. A later response, the negative component N170, also has
      lower latency in the case of faces than in inversion and objects. Its amplitude
      increases when the faces are inverted due to the generation of a greater
      activation in the region where it originates. A later negative potential can be
      associated to semantic identification in face recognition. The N170 waves in
      autistic individuals display greater latency with faces that is similar to the
      response to objects and, in turn, show no differences in the latencies with
      inverted faces. It remains to be shown whether they have an N400 response to
      faces. CONCLUSIONS: Cognitive evoked potentials allow us to evaluate face
      recognition both in normal and autistic individuals by presenting responses to
      specific stimuli. Further studies will enable us to determine whether an N400
      response exists in individuals with autism.

PMID- 15736081
TI  - [Movement disorders in Rett syndrome].
AB  - INTRODUCTION: Rett syndrome is a progressive neurodevelopmental disorder with
      onset in early childhood occurring almost exclusively in females and caused by
      mutations in methyl-CpG- binding protein 2 (MECp2) and is one of the most
      frequent causes of mental retardation in females. Regression is a defining
      feature of Rett syndrome and during the regression period the patients develop
      autistic behaviour. This is the reason why Rett syndrome has been classified as a
      pervasive developmental autistic spectrum disorder. However movement disorders
      are so exuberant, characteristic and unique in Rett syndrome that is very
      difficult to an experienced clinician mistake both situations. DEVELOPMENT: We
      can define Rett syndrome as a condition which manifests in the majority of the
      cases as a hyperkinetic movement disorder and progresses (at varying rates) to a
      bradykinetic disorder. The aim of this publication is to characterize and
      describe movement disorders in Rett syndrome based on a revision of the
      literature and the personal experience of the author.

PMID- 15736082
TI  - [The neuropsychological phenotype of attention deficit hyperactivity disorder:
      are there differences among subtypes?].
AB  - INTRODUCTION: Recent studies suggest that the ADHD subtypes would be best
      conceptualized as separate clinical entities, based on their epidemiology,
      central and associate symptomatology. OBJECTIVES: To determine the differences
      and similarities between subtypes in its associate symptomatology, specifically
      in the neuropsychological phenotype of executive dysfunction. PATIENTS AND
      METHODS: A group of children between 6 and 14 years of age with a diagnosis of
      ADHD-innattentive subtype (DESAT, n = 20) and another with ADHD-combined subtype
      (COMB, n = 39). RESULTS: Overall, the COMB subject sample displayed lower
      performance than DESAT group. Statistically significant differences were found in
      Kaufman-ABC-hands movement subtest, Wisconsin Card Sorting Test (WCST)-total
      error and WCST-conceptual level. CONCLUSIONS: The subtypes differ significantly
      in measures or non verbal working memory, hindsight, foresight, and motor
      control. Both groups share a deficit in response output speed and verbal working
      memory. We hypothesized areas of cognitive superiority for each subtype: spatial
      memory for the inattentive and gestaltic composition for the combined. Results
      provide evidence to support quantitative and qualitative differences in the
      neuropsychological profile between the ADHD-innatentive and combined subtypes.

PMID- 15736083
TI  - [Antiepileptic drugs in the treatment of autistic regression syndromes].
AB  - INTRODUCTION AND DEVELOPMENT: It is still not known whether epilepsy or
      subclinical epileptiform activity can generate autistic regression in children
      with pervasive development disorder (PDD) in a similar manner to the way
      linguistic and neurocognitive regression are produced in patients with Landau
      Kleffner syndrome and electrical status epilepticus during slow-wave sleep
      (ESES). Data on the use of different antiepileptic drugs (AED) in Landau-Kleffner
      syndrome and in ESES is contradictory, but it has been proved that courses of
      polytherapy clearly have a harmful effect. It has been suggested that the
      suppression of subclinical epileptiform activity by the early use of AED can
      revert the disorders affecting behaviour, cognition and language in these
      patients. Nevertheless, few studies have been conducted to examine the influence
      of AED therapy on the clinical course of children with PDD and autistic
      regression and evidence of epileptiform activity in video-EEG-polygraph
      recordings during sleep. Cases of complete recovery or significant improvement
      following the use of AED such as valproate, ethosuximide, clobazam,
      oxcarbazepine, sulthiame, levetiracetam, topiramate or lamotrigine have been
      reported. Moreover, striking and sustained improvements have been reported with
      courses of corticoids or ACTH. Yet, we still do not know whether the natural
      history of PDD with autistic regression is linked to the persistence of
      epileptiform anomalies in the video-EEG-polygraph recordings or not, and it is
      therefore difficult to draw conclusions about whether early AED therapy should be
      established in these patients. CONCLUSIONS: In our own clinical experience,
      lamotrigine has proved to be a good therapeutic alternative for the treatment of
      patients with autistic regression and paroxysmal anomalies in the EEG recordings,
      and offers a suitable balance between effectiveness and safety.

PMID- 15736084
TI  - [Educational intervention in autism from a psychological point of view].
AB  - INTRODUCTION: Autism is the prototypical condition in autism spectrum disorders.
      It is a developmental disorder of biological origin that becomes apparent by the
      age of 3 and which is characterised by qualitative alterations affecting the
      development of social relations and interaction, communication and language, and
      the development of symbolic and imaginative activity. DEVELOPMENT: The first
      manifestations of the disorder take place, in most cases and according to the two
      sources of information currently available (retrospective information provided by
      the families and the analysis of family videos), around the end of the first year
      (the age of 18 months is one of the ages most frequently mentioned by the
      families when asked about the matter). From an ontogenetic point of view, the
      coincidence between the times of the first manifestations of the disorder and the
      development of qualitatively human psychological functions is significant. Autism
      can, therefore, be understood to be a disorder that affects the genesis of
      psychological factors that are extremely relevant to human development and, thus,
      educational intervention must necessarily include the construction of these
      psychological functions as far as this is possible. CONCLUSIONS: Educational
      treatment in autism and in autism spectrum disorders have to be based on two
      essential areas of knowledge that must guide the implementation of any
      intervention programme, i.e. developmental and ontogenetic knowledge of typical
      development and knowledge of the autistic way of 'being'. The essential part of
      the treatment carried out in autism lies in the flexible and creative integration
      of our knowledge in these two areas.

PMID- 15736085
TI  - [Autism: educational models for a quality life].
AB  - AIMS: Our aim is to describe the change that is taking place in the field of
      education in developmental disabilities from models centred on the clinical
      symptoms and on the limitations in the adaptive skills to models that focus on
      valuable personal results in terms of quality of life. DEVELOPMENT: In order to
      understand these changes, we outline some of the key points that have given rise
      to a particular cultural construction of disability and we also discuss how the
      situation is changing towards models aimed at achieving important personal
      results. In autism, as in the other developmental disorders, special emphasis has
      traditionally been placed on an education focusing on symptoms and on skills,
      and, although things are now beginning to head in that direction, little
      attention has been given to education based on the person and his or her quality
      of life. These changes imply new roles for the professionals attending these
      people. These roles involve combining technique with empathy and ethics, and they
      are more firmly based on the active role of individuals with autism, together
      with their rights, interests and opinions. CONCLUSIONS: Models of intervention
      must pay special attention to the pursuit of valuable personal results, which are
      oriented towards living a quality life and must involve the active participation
      of the individuals themselves as well as their relatives.

PMID- 15736086
TI  - [Large-scale genotyping in research into autism spectrum disorders and attention
      deficit hyperactivity disorder].
AB  - INTRODUCTION AND DEVELOPMENT: Autism spectrum disorder (ASD) and attention
      deficit hyperactivity disorder (ADHD) are two neuropsychiatric disorders
      beginning in childhood that present a high degree of familial aggregation. ASD is
      characterised by social interaction and communication disorders, whereas patients
      with ADHD display persistent inattention and/or hyperactive-impulsive behaviour.
      With the exception of a few cases of autism in which cytogenetic anomalies or
      mutations have been reported in specific genes, the aetiology of these diseases
      remains unknown. This is a group of multifactorial diseases with several genes
      having a lesser effect and there is also an environmental component. Genetic
      linkage studies have pointed to about 20 chromosomal regions that could well
      contain genes that grant susceptibility to autism, to ADHD or to both disorders.
      The challenge to researchers lies in the clinical characterisation, recruitment
      of patients with ASD and ADHD, gene dosage quantification studies, comparative
      genomic methylation and hybridisation in order to identify chromosomal
      rearrangements in patients with autism and severe mental retardation.
      CONCLUSIONS: Genotyping large SNP-type collections that are potentially
      functional in genes that are candidates for these disorders, based on
      pharmacological, biochemical and neuropathological data together with that coming
      from animal models and linkage studies in a wide collection of samples from
      patients and controls, will enable us to identify the genetic components of these
      pathologies and to define their biological foundations.

PMID- 15736088
TI  - [Hyperactivity in preschoolers: a clinical description].
AB  - INTRODUCTION: Hyperactivity is a behavioural development disorder characterised
      by disruptive motor activity that prevents the individual from establishing
      adequate social ties and normal communication, which are an essential part of a
      child's overall development. It is an unspecific symptom of several
      neurocognitive disorders, the most frequent of which is attention deficit
      hyperactivity disorder (ADHD). PATIENTS AND METHODS: We present the results of
      two investigations. In the first, a case-control study, we conducted a
      comparative analysis of how the parents of 50 children diagnosed with ADHD
      remember the behaviour of their children during the first 12 months of their
      lives. The symptoms were separated into 3 clinical profiles (daytime
      irritability, eating disorders and sleep dysfunctions). Up to 33% of the families
      reported a history of at least one of these aspects. 41% of the children were
      described as being excessively restless, crying a lot or irritability, and being
      easily startled and very sensitive to noises, and 42.7% had difficulty in getting
      to sleep or displayed intermittent periods of sleep and woke up crying. For the
      second research project, which was to complement the previous one, we designed a
      survey which was answered by the parents of 78 patients diagnosed with ADHD. The
      questionnaire collected information about the first 5 years of life in 4 sections
      (28 items): behaviour up to the age of one year, psychomotor development,
      development of play, and the parents' general perception of their child
      (distracted-inattentive, impulsive, destructive, immature, negativist,
      oppositional, other). The Rasch mathematical model was used to obtain the
      clinical profile of the case mix. CONCLUSIONS: The clinical symptoms appear on a
      continuum throughout the early years of the child's life. The results of our
      experience allow us to develop a method of clinical examination focused on the
      evaluation of the individual's development, play, and communication and
      socialisation skills which can be used to approach the differential diagnosis of
      the hyperactive preschooler.

PMID- 15736087
TI  - [Epidemiological research in autism: an integrative view].
AB  - INTRODUCTION: Sixty years after the first descriptions of Autism, the same
      diagnostic criteria based on clinical observation used then are still valid
      today. Two years ago, the Instituto de Salud Carlos III set up the Grupo de
      Estudio en los Trastornos del Espectro Autista (Autism Spectrum Disorders Study
      Group) with the aim of evaluating the current state of research in autism
      spectrum disorders (ASD) in Spain. This group established collaborative links
      with different associations and set up a way of working that was more coordinated
      and closer to the real day-to-day situation experienced by the families involved.
      AIMS AND DEVELOPMENT: The aim of this review is to update certain areas of
      knowledge concerning the distribution of the factors that determine ASD, that is
      to say, about the epidemiology of these disorders. At the same time, it intends
      to arouse a greater degree of interest among professionals who are more directly
      involved in the study of pervasive developmental disorders. The latest diagnostic
      tools offer a higher degree of certainty in the complicated process of evaluating
      a case with symptoms of autism. Nevertheless, given the effectiveness of early
      attention and how it affects the prognosis, population-based ASD screening
      programmes must be implemented. These would have to include the use of Modified
      Check List for Autism in Toddlers (M-CHAT)-type questionnaires, followed by
      several levels of diagnosis, in order to reduce the number of false positives
      while at the same time increasing the true positives.

PMID- 15736089
TI  - [Neurodevelopmental disorders and epilepsy].
AB  - INTRODUCTION AND DEVELOPMENT: Neurodevelopmental disorders and the epilepsies
      share common etiologies and pathologies. The severity of impairment and the
      variety of symptoms associated with neurodevelopmental disorders or with
      particular epilepsy syndromes reflect focal or global, structural or functional
      dysfunction of neuronal networks. The complex relationship between
      neurodevelopmental disorders and epilepsy is secondary to common factors that
      include genetics, cognition, motor and language function. The epileptic
      encephalopathies are associated with regression or slowing of cognitive, language
      or behavior and the accepted working hypothesis is that this is a direct
      consequence of the seizures or of the interictal epileptiform activity, as
      opposed to the associated medical condition. The evidence that recurrent seizures
      or abnormal electrical activity can cause specific cognitive, language or
      behavioral abnormalities even in accepted epileptic encephalopathies is still
      controversial. Data from animal studies and the clinical experience from
      epileptic encephalopathies of early life imply that there are developmental time
      windows crucial to the type of epilepsy syndrome and to cognitive and behavioral
      outcome. CONCLUSION: The management of children in whom a neurodevelopmental
      disorder coexists with epilepsy is a difficult problem that requires a
      multidisciplinary approach that addresses both the epilepsy and the specific
      cognitive or behavioral problem and is tailored to the needs of the individual
      child.

PMID- 15736090
TI  - [Memory and attention in children with brain dysfunction].
AB  - INTRODUCTION: For conscious behaviours to continue, attention and working memory
      must be brought into play in order to match the data from the current reality
      with those in the long-term memory and to the sequential plans for adaptive
      action. PATIENTS AND METHODS: We present the preliminary findings of our study of
      50 patients between 7 and 16 years of age, who were divided into three groups
      according to their dominant neurocognitive disorder: a 'pure' ADHD group, an
      ADHD/LD group (with comorbid learning disorder) and an RMEM (risk of memory
      disorder due to bilateral temporomesial damage) group. All of them were
      administered a battery of tests designed to evaluate attentional control and
      short and long-term memory. RESULTS: Verbal IQ was above 80 in all the
      participants, with no differences among the three groups. The ADHD/LD group had a
      manipulative IQ and level of sustained attention below those of the ADHD group,
      but no long-term memory deficit was observed in either of these two groups. In
      contrast, the RMEM group's performance was poorer in verbal memory tasks,
      although their behaviour is more attentive and stable compared to that of the
      other two groups. CONCLUSIONS: Neuropsychological analysis of these dissociations
      allows adjustments to be made in the strategies for therapeutic interventions.
      Performance in long-term learning in children with ADHD and ADHD/LD can be
      improved with psychostimulants owing to the activating effect they have on
      working memory.

PMID- 15736091
TI  - [The value of cognitive evoked potentials in assessing the effectiveness of
      methylphenidate treatment in children with attention deficit hyperactivity
      disorder].
AB  - AIM: To investigate the changes of the latency and amplitude of P300 in relation
      to methylphenidate (MPH) medication. SUBJECTS AND METHODS: 36 children with
      attention deficit hyperactivity disorder (ADHD) and 18 children as control group
      were tested with an auditory and visual oddball paradigm both before and 1.5 h
      after a single dose trial of MPH. RESULTS: MPH increased the amplitude and the
      latency of the visual and auditory P300 component In the ADHD group the latency
      of the P300 component was longer and the amplitude smaller than in the control
      group. CONCLUSION: These results suggests that MPH acts to improve processing of
      cognitive information in children with ADHD where no differences with normal
      children are present.

PMID- 15736092
TI  - [Recent contributions from magnetoencephalography to the neurobiology of
      attention-deficit/hyperactivity disorder].
AB  - INTRODUCTION AND DEVELOPMENT: Current theories postulate that the core cognitive
      deficit in attention-deficit/hyperactivity disorder (ADHD) is an executive
      dysfunction. Neuroimaging studies on the whole have provided both anatomical and
      functional evidence supporting the fronto-striatal dysfunction hypothesis in
      ADHD. However, recent neuroimaging studies have found anatomical and functional
      impairments in posterior cortical regions, such as the inferior parietal and
      posterior temporal cortices, which have been related to a deficit in selective
      attention. Event related potential (ERP) studies show that ADHD children have an
      impairment in early components (within the first 200 ms of processing), such as
      P1 or N1, both of which are sensitive to selective attention effects. These
      findings cast doubt regarding the fronto-striatal/executive dysfunction as the
      core deficit in ADHD. CONCLUSIONS: One of the main objectives of ADHD research is
      the search for its core cognitive deficit and the neural networks underlying it,
      because it has important repercussions over ADHD diagnosis and treatment. High
      temporal resolution techniques, such as ERP or magnetoencephalography may be
      particularly useful in distinguishing the precise moment of cognitive processing
      during which the brain activity of children with ADHD begins to be impaired. As a
      consequence, this may help to elucidate the core cognitive deficit in ADHD.

PMID- 15736093
TI  - [Attention deficit hyperactivity disorder therapy update: extended-release
      methylphenidate].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a very common
      condition in neuropaediatric practice and the most widely used medication is
      methylphenidate (MPT). We discuss the comorbid disorders, diagnosis,
      aetiopathology and neurochemical bases, and we also stress the importance of
      pharmacological action on the dopaminergic and noradrenergic pathways, and the
      problems and benefits of the different formulations of MPT. AIMS: Since extended
      release MPT by means of the OROS technique has only recently been commercialised
      in Spain, we conducted a comparative analysis of immediate-release MPT and
      extended-release MPT in a series of 93 patients in order to determine which of
      them is preferable, to evaluate the reasons why this is so, and to analyse the
      shortcomings and advantages of the two drugs. PATIENTS AND METHODS: We present a
      study of 93 patients between 6 and 18 years old. Once an initial treatment had
      been established, changing over to extended-release MPT was proposed. We analysed
      compliance, effectiveness, safety, the preferences of the family and the degree
      of control over afternoon symptoms with the new treatment. RESULTS AND
      CONCLUSIONS: Most of the patients began treatment with immediate-release MPT or
      other medication. Changing to extended-release MPT brought about greater
      satisfaction with the control of afternoon symptoms and an improvement in the
      degree of compliance with respect to the initial treatment with immediate-release
      MPT or other drugs.

PMID- 15736094
TI  - [The contribution of the cerebellum to cognitive processes].
AB  - INTRODUCTION: Apart from its functions involving control over movement, the
      cerebellum is also related to learning motor sequences and, according to the
      experimental and clinical evidence we will examine, to cognitive and learning
      processes that do not exclusively involve motor activity. DEVELOPMENT: The
      cerebrocerebellar connections act as a vehicle for the afferent information from
      the sensory-motor cortex, prefrontal cortex, the frontal regions responsible for
      (expressive) language, parietal cortex, superior colliculus and superior temporal
      cortex, returning efferences to similar areas that are responsible for attention,
      visuospatial perception, memory and the regulation of executive and emotional
      functions. It plays a role in the preparation and anticipation of motor
      responses, according to sequences experienced previously depending on the
      information received from the surroundings, thus anticipating the physiological
      state for carrying out perceptual motor or cognitive tasks. A number of
      experimental neuroimaging studies, as well as the discovery of a new cell in the
      neuronal population of the cerebellum, relate the cerebellum to cognitive
      processing. CONCLUSIONS: Clinical observation of patients with cerebellar lesion
      or dysfunction, which are related to a deficit in the cognitive functions,
      suggests a model with which to understand these mechanisms. Long-lasting
      depression is considered to be the learning mechanism in the cerebellum and is
      intimately related to the mechanisms involved in neuronal plasticity and in
      memory.

PMID- 15736095
TI  - [Neurological follow-up of the preterm infant].
AB  - AIMS: Our aim was to evaluate the presence, type and severity of neurological
      sequelae in infants born prematurely. SUBJECTS AND METHODS: A descriptive,
      retrospective study was conducted in which we reviewed the patient records of 179
      patients with a history of prematurity who visited the Child Neurology clinic at
      COLSANITAS in Bogota between 1st January 2000 and 31st July 2004. Data was
      collected concerning demographic aspects, maternal and foetal risk factors,
      perinatal complications, age at the last Child Neurology control, type of sequela
      and severity. The variables and their relation to neurodevelopmental disorders
      were analysed. RESULTS: Of the 179 patients analysed, 51% were males and the
      remaining 49% were females. The average gestational age was 31.8 weeks. Average
      weight at birth was 1,690 g. No statistically significant associations were found
      among the variables that were analysed. CONCLUSIONS: The results obtained differ
      from those reported in the literature from around the world. This is due to the
      fact that the sample population belongs to a minority living in privileged
      socioeconomic conditions, which does not represent the real situation of the
      Columbian population. In addition, the high percentage of patients who drop out
      of the follow-up programmes makes it difficult to check the sequelae. With the
      data obtained we are considering the possibility of extending the neurological
      follow-up until the age of 6 years or up to the age at which the patient is
      completely adapted to full-time education.

PMID- 15736096
TI  - [Intrathecal baclofen and Botulinum toxin in infantile cerebral palsy].
AB  - INTRODUCTION: Infantile cerebral palsy is considered to be a motor disorder
      affecting both posture and movement. It is the manifestation of a cerebral lesion
      that took place during the maturing process of the brain. Spastic cerebral palsy
      is the most frequent variety. The spasticity presented by these patients strongly
      influences their functioning and gives rise to several complications that affect
      their quality of life. AIMS AND DEVELOPMENT: The main aim of this study is to
      determine a set of suitable and effective therapeutic steps that can be used to
      improve patients' spasticity and to prevent the complications that stem from
      them, such as contractures, deformities, surgery, etc. Multiple treatments were
      used, including physiotherapy, rehabilitation and oral pharmacotherapy, with few
      satisfactory results. At present there are two very promising therapeutic
      alternatives for patients with infantile cerebral palsy: Botulinum toxin, which
      we already have a great deal of experience with, and intrathecal treatment with
      baclofen. We report on a series of 10 patients aged between 8 and 15 years who
      had had an intrathecal baclofen infusion pump implanted. To date (maximum follow
      up: 12 months), their clinical course has been satisfactory in most cases, with
      no severe complications related to the surgical technique, except in one
      individual who presented a fistula that resolved spontaneously. CONCLUSIONS:
      Intrathecal baclofen seems to be a very useful alternative in the treatment of
      spasticity to improve the quality of life of these patients and those around
      them.

PMID- 15736097
TI  - [Movement disorders of functional origin (psychogenic) in children].
AB  - PATIENTS AND METHODS: Sixteen cases of functional (psychogenic) pediatric
      movement disorders (PMD) have been analyzed. They represents 2.4% of a PMD
      personal series (age of onset less than 18). RESULTS: Apart from a case, age of
      onset was older than 10 years. 81% (13/16 cases) were females. Tremor (68%) was
      the predominant abnormal movement followed by mioclonus. These facts are
      according with the scarce studies reported of functional PMD. We emphasize the
      diagnostic difficulties of this kind of conditions. CONCLUSIONS: Diagnostic clues
      are age of onset older than 10 years, female gender, clinical inconsistency of
      the movement, increasing or decreasing of the movements with attention to the
      movements or distraction, normality of the exams including neurophysiological
      studies. However in some cases a follow-up is necessary to confirm the diagnosis.

PMID- 15736098
TI  - [Working memory in basic learning processes].
AB  - INTRODUCTION AND DEVELOPMENT: Working or operative memory is considered to be a
      distinctive element of executive functioning. Nowadays, thanks to neuroimaging
      studies, it is known that the dorsolateral prefrontal cortex plays a crucial role
      in working memory. It has been observed that during the intervals when
      information is being retained, intense and persistent activity is going on in the
      region, as shown by the delayed response times. Working memory is fundamental for
      the analysis and synthesis of information, the retention of data needed to
      perform a particular mental process, carrying out priming (impression in memory
      of something that has been experienced, such as words, objects or events, for
      example), carrying out pre-functional tutoring activities and post-functional
      monitoring. CONCLUSIONS: Disorders affecting the fundamental mechanisms of
      working memory will give rise to a dysfunction that will exert an influence on
      innumerable formal academic learning processes such as difficulty in focusing
      attention, difficulty in inhibiting irrelevant stimuli, difficulty in recognising
      priority patterns, inability to recognise hierarchies and the meaning of stimuli
      (analysis and synthesis), problems in establishing an intention, and difficulty
      in recognising and selecting the goals that are best suited to solving a problem.
      It will also involve the impossibility to establish a plan to achieve goals,
      inability to analyse the activities required to accomplish an objective and
      difficulties in carrying out a plan, since it becomes impossible to monitor or
      modify the task to fit the original plans.

PMID- 15736099
TI  - [Non-verbal learning disorder. Clinical features to guide diagnosis].
AB  - AIMS: The development and multiplication of information about learning disorders
      leads to the need to systematise the knowledge available and to base it on the
      clinical data. DEVELOPMENT: Apart from trouble-free diagnoses, non-verbal
      learning disorders are characterised by their high comorbidity rate. They are
      associated to attention deficit with or without hyperactivity, motor coordination
      disorder, dyscalculia, problems with social development and also, to a certain
      extent, oral and written language disorders. Depending on countries, a child with
      a good fundamental intellectual capacity and good development of language, but
      motor clumsiness and low visuospatial skills with or without relational
      difficulties can be diagnosed in different ways. In this study, after briefly
      reviewing the literature on comorbidity and the contexts of the work, we propose
      a set of guidelines for basic examination that can be used in visits due to
      learning disorders, including suggestive history, areas that require detailed
      questioning, and central tests. CONCLUSIONS: Partly because of the comorbidity,
      following the introductory visit, only a multidisciplinary team can study a child
      with non-verbal learning disorder properly, using specific tests to pinpoint the
      profile of their difficulties; their strong points should also be stressed.

PMID- 15736100
TI  - [Written language and intellectual disability].
AB  - AIMS: Following the diagnosis of intellectual disability, a prognosis can be
      offered concerning the degree of autonomy the child will be able to achieve based
      on prior experience, but which depends on the aetiology of the disability. It is
      still difficult to give a prospective answer regarding the capacity to reach an
      operative level of written language. The goal of being able to offer an
      experience-based prognosis involves prior analysis of how learning dysfunctions
      are approached in the disabled population. DEVELOPMENT: Although we have an
      increasingly deeper understanding of the neurocognitive foundations of specific
      learning difficulties and the careful neuropsychological management of children
      with disorders affecting the acquisition of written language with a typical
      intellectual level, those with intellectual disability continue to be treated
      using a simplistic approach in which their intelligence quotient is still taken
      as the most relevant feature. Little attention is paid to neuropsychological
      aspects, the pedagogical and social environment or comorbid aspects that may
      affect the acquisition of the function. Yet, these are aspects that are submitted
      to thorough evaluation in children who are not disabled. CONCLUSIONS: The current
      concept of intellectual disability has gone beyond the definition based on the
      intelligence quotient. The wide variability in the reading function in children
      with intellectual disability cannot be explained only according to a psychometric
      assessment. A more complete neuropsychological approach, as carried out in the
      population with no disability, will enable us to detect cognitive, pedagogical,
      social and pathological dysfunctions that interfere with the acquisition of
      written language.

PMID- 15736101
TI  - [New trends in the evaluation of mathematics learning disabilities. The role of
      metacognition].
AB  - INTRODUCTION: The current trends in the evaluation of mathematics learning
      disabilities (MLD), based on cognitive and empirical models, are oriented towards
      combining procedures involving the criteria and the evaluation of cognitive and
      metacognitive processes, associated to performance in mathematical tasks. AIMS:
      The objective of this study is to analyse the metacognitive skills of prediction
      and evaluation in performing maths tasks and to compare metacognitive performance
      among pupils with MLD and younger pupils without MLD, who have the same level of
      mathematical performance. Likewise, we analyse these pupils' desire to learn.
      Subjects and methods. We compare a total of 44 pupils from the second cycle of
      primary education (8-10 years old) with and without mathematics learning
      disabilities. RESULTS: Significant differences are observed between pupils with
      and without mathematics learning disabilities in their capacity to predict and
      assess all of the tasks evaluated. As regards their 'desire to learn', no
      significant differences were found between pupils with and without MLD, which
      indicated that those with MLD assess their chances of successfully performing
      maths tasks in the same way as those without MLD. Finally, the findings reveal a
      similar metacognitive profile in pupils with MLD and the younger pupils with no
      mathematics learning disabilities. CONCLUSIONS: In future studies we consider it
      important to analyse the influence of the socio-affective belief system in the
      use of metacognitive skills.

PMID- 15736102
TI  - Altered response of insulin-like growth factor-binding protein 1 to nutritional
      deprivation in type 2 diabetes mellitus.
AB  - Circulating insulin-like growth factor-binding protein 1 (IGFBP-1) normally has a
      close inverse relationship to insulin secretion, which results in a
      characteristic diurnal variation. However, in type 2 diabetes the correlation
      with insulin may be lost and IGFBP-1 concentrations relatively increased. The aim
      of this study was to determine the effect of nutritional deprivation on the
      diurnal patterns of IGFBP-1 regulation in type 2 diabetes mellitus. After a
      baseline assessment period, food intake was reduced over 48 hours to 627.6 kJ/d
      (150 kcal/d) for 72 hours and increased again over 24 hours to baseline
      (refeeding). Blood samples were taken at 2-hour intervals, for 24 hours in the
      baseline period, 48 hours during nutritional deprivation, and 24 hours during
      refeeding. Six individuals with type 2 diabetes were compared with 2 groups that
      were selected for normal fasting glucose and insulin levels and comprised 6 obese
      and 6 lean subjects. During energy (caloric) restriction, fasting insulin levels
      decreased to a similar extent in each study group. At baseline, IGFBP-1
      concentrations were similar in each of the study groups and at the end of the
      period of energy (caloric) restriction the 6:00 AM fasting levels had increased
      by 144% in the obese control group and by 245% in the lean individuals (each P <
      .001). In the patients with type 2 diabetes there was a blunted increase in IGFBP
      1 concentrations with nutritional deprivation by 33% compared with baseline.
      During refeeding after nutritional deprivation the IGFBP-1 response to insulin
      was restored in the individuals with diabetes. In conclusion, patients with type
      2 diabetes mellitus have altered IGFBP-1 regulation, relating to impaired hepatic
      insulin sensitivity, which improves after a period of energy (caloric)
      restriction.

PMID- 15736103
TI  - Correlation between the adiponectin-leptin ratio and parameters of insulin
      resistance in patients with type 2 diabetes.
AB  - We studied the correlation between the adiponectin-leptin (A/L) ratio and
      parameters of insulin resistance in 220 Japanese patients with type 2 diabetes
      (138 men and 82 women). Body mass index (BMI), triglycerides (TGs), HDL
      cholesterol (HDL), and preheparin serum lipoprotein lipase (LPL mass) were
      examined as laboratory parameters of the insulin resistance. The correlations
      between these laboratory parameters and adiponectin, leptin, or A/L ratio were
      studied. Adiponectin levels correlated significantly with BMI (r = -0.298, P =
      .0003), TGs (r = -0.221, P = .0092), HDL (r = 0.31, P = .0002), and LPL mass (r =
      0.26, P = .0021) in men, and with TGs (r = -0.29, P = .0093), HDL (r = 0.239, P =
      .0338), and LPL mass (r = 0.499, P < .0001) in women. Leptin levels correlated
      significantly with only BMI (r = 0.31, P = .0002) in men, and with BMI (r = 0.71,
      P < .0001) and TGs (r = 0.26, P = .0201) in women. Adiponectin and leptin levels
      tended to correlate with these parameters in an opposite manner. On the other
      hand, A/L ratio significantly correlated with BMI (r = -0.4, P < .0001), TG (r = 
      0.199, P = .0192), HDL (r = 0.235, P = .0054), and LPL mass (r = 0.244, P =
      .0390) in men, and with BMI (r = -0.482, P < .0001), TG (r = -0.402, P = .0002),
      HDL (r = 0.358, P = .0011), and LPL mass (r = 0.487, P < .0001) in women. Next,
      the patients were divided into 3 groups classified by their fasting plasma
      glucose (FPG) level, and the correlations between the parameters and A/L ratio or
      homeostasis model assessment (HOMA-R), and the correlation between A/L ratio and
      HOMA-R were investigated in each group. Significant correlations between the
      parameters and A/L ratio were tended to be observed as the FPG level rose;
      however, the significant correlations between the parameters and HOMA-R were no
      longer seen as FPG level elevated. The results suggested that the A/L ratio was
      effective in relevance as a parameter of insulin resistance to adiponectin or
      leptin alone, and a more sensitive and reliable marker of insulin resistance than
      HOMA-R as the FPG level elevated, in patients with type 2 diabetes.

PMID- 15736104
TI  - Expression levels and functional aspects of the hyaluronan receptor CD44. Effects
      of insulin, glucose, IGF-I, or growth hormone on human arterial smooth muscle
      cells.
AB  - An increased amount of hyaluronan (HA) in the arterial wall is a feature of the
      diabetic macroangiopathy. The functional consequences of accumulated HA are
      mediated through binding to CD44. The regulation of this receptor by diabetic
      metabolic and hormonal factors is, however unknown. The objective of this study
      was to examine the influence of glucose, insulin, insulin-like growth factor I
      (IGF-I), and human growth hormone (hGH) on the formation and function of the HA
      receptor CD44 in cultures of human aortic smooth muscle cells (SMCs). Migration
      of nonproliferating SMCs were determined by estimating the area covered by cells
      6 days after removal of a barrier. Cellular content of standard CD44 and its
      isoforms, CD44v3 and CD44v6, and HA-binding capacity were measured using a
      modified enzyme-linked immunosorbent assay procedure. The analysis is made either
      with antibodies against CD44 or with HA as a ligand. The migration assay showed
      that glucose, insulin, and IGF-I were able to stimulate SMC migration (2 P <
      .01). Anti-CD44 antibody inhibited the stimulated migration at most
      concentrations. Insulin increased HA binding at 100 to 1000 micro U/mL insulin (2
      P < .03). CD44 expression was only elevated at 1000 micro U/mL insulin (2 P <
      .03), whereas CD44 content decreased at 2 ng/mL hGH and increased at 16 ng/mL hGH
      (2 P < .01). Glucose and IGF-I reduced the amount of the variant isoform CD44v3
      (2 P < .01) but did not change the amount of total CD44. CD44v6 was not present
      on human arterial SMCs. In conclusion, the present data obtained with human
      arterial SMCs in vitro support a role of CD44 and its isoform, CD44v3, in the SMC
      response to the metabolic and hormonal disorders of diabetes.

PMID- 15736105
TI  - GPR40 gene Arg211His polymorphism may contribute to the variation of insulin
      secretory capacity in Japanese men.
AB  - GPR40 is a member of the G-protein-coupled receptors. Recent studies suggest that
      GPR40 is highly expressed in pancreatic beta cells and insulin-secreting cell
      lines, and that fatty acids increase intracellular calcium concentration and
      amplify glucose-stimulated insulin secretion by activating GPR40. Despite
      identification of the Arg211His polymorphism in the GPR40 gene, there have been
      no clinical studies concerning this polymorphism. The present study was performed
      to investigate the effects of the GPR40 gene Arg211His polymorphism on clinical
      and metabolic parameters, including serum insulin level, in 327 healthy Japanese
      men, using the TaqMan polymerase chain reaction method. Serum insulin level,
      homeostasis model of insulin resistance (HOMA-IR), and beta-cell function (HOMA
      beta were significantly different (P = .0075, .0152, and .0039, respectively) and
      were lowest in Arg/Arg homozygotes and highest in His/His homozygotes, although
      plasma glucose and serum lipids were not significantly different. Multiple
      regression analyses showed that serum insulin level, HOMA-IR, and HOMA- beta were
      significantly correlated with this polymorphism after adjusting for age and body
      mass index. After Bonferroni's correction for multiple comparisons was made, only
      HOMA- beta was significantly different among the 3 genotypes. These results
      suggest that the Arg211His polymorphism in the GPR40 gene may contribute to the
      variation of insulin secretory capacity in Japanese men.

PMID- 15736106
TI  - Propylthiouracil and thiamazole do not alter in vitro neutrophil oxidative burst.
AB  - Propylthiouracil and thiamazole are thionamides used in the treatment of
      hyperthyroidism. In addition to reducing thyroid hormone synthesis, these drugs
      have other activities that improve the hypermetabolic state of the patients as
      well as adverse and toxic effects. The capacity of these 2 drugs to interfere
      with the production of reactive oxygen species of human neutrophils exposed in
      vitro to these drugs was evaluated. The production of reactive oxygen species was
      assessed by chemiluminescence assays and the cells were stimulated with zymosan
      particles opsonized with a pool of normal human serum. No alteration was found in
      the chemiluminescence response of treated human neutrophils when compared to
      controls. The results show that these drugs, at the studied concentrations and
      with the experimental approach used, have no direct effect on the production of
      oxidative burst of neutrophils. We conclude that if these drugs have any action
      on the oxidative metabolism of neutrophils these might include some
      metabolization steps that do not take place in this in vitro model.

PMID- 15736107
TI  - Red wine consumption improves insulin resistance but not endothelial function in
      type 2 diabetic patients.
AB  - Epidemiological studies have shown that red wine consumption is associated with
      less cardiovascular mortality in the general population and in the diabetic
      patients. To determine whether red wine improves insulin resistance in diabetic
      patients and to explore the relation between insulin sensitivity and endothelial
      function, we studied vascular reactivity and insulin-mediated glucose uptake in 9
      type 2 diabetic patients before and after 2 weeks of red wine consumption (360
      mL/d, wine-treated diabetics) and 8 type 2 diabetic patients who did not consume
      wine (control diabetics). Vascular reactivity was evaluated by plethysmography
      during intraarterial infusion of acetylcholine (Ach), sodium nitroprusside, and L
      N-monomethylarginine. Forearm nitrite balance was measured during Ach infusion.
      Insulin sensitivity was measured by euglycemic hyperinsulinemic clamp at 1 mU/kg
      per minute. The basal forearm blood flow and the response to Ach, to sodium
      nitroprusside, and to L-N -monomethylarginine were unchanged both in the wine
      treated and in the control diabetics. In contrast, insulin-mediated whole body
      glucose disposal improved by 43% after red wine consumption (from 2.79 +/- 0.4 to
      4.02 +/- 0.5 mg/kg of lean body mass per minute, P = .02), but did not change in
      the control group. In conclusion, red wine consumption for 2 weeks markedly
      attenuates insulin-resistance in type 2 diabetic patients, without affecting
      vascular reactivity and nitric oxide production.

PMID- 15736108
TI  - The effects of rosiglitazone and metformin on the plasma concentrations of
      resistin in patients with type 2 diabetes mellitus.
AB  - Resistin is a protein secreted from adipose tissue that is thought to play a role
      in insulin sensitivity. We examined the effects of rosiglitazone and metformin on
      the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients
      with type 2 diabetes mellitus who showed poor glycemic control with glimepiride
      (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid)
      treatment groups. All subjects continued glimepiride treatment as well. The
      plasma concentrations of resistin were measured at baseline and at 6 months of
      treatment for both groups. The anthropometric parameters, fasting plasma glucose,
      HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol,
      free fatty acids, and adiponectin concentrations were also measured. After 6
      months of treatment, the reduction in plasma glucose levels was similar between
      the 2 groups. There were no significant changes in the lipid profiles of either
      group during the study period. The plasma resistin levels decreased in the
      rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P < .05) but increased
      in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P < .05). The
      plasma adiponectin concentrations were increased in the rosiglitazone group (2.91
      +/- 1.46 vs 4.23 +/- 1.77 microg/ml; P < .05) but were unchanged in the metformin
      group. In summary, rosiglitazone treatment decreased the plasma resistin levels
      whereas metformin treatment increased them in patients with type 2 diabetes
      mellitus showing poor glycemic control with sulfonylurea therapy. These results
      suggest that the observed changes in plasma resistin levels are not the
      consequences of improved insulin resistance, nor are they consequences of
      glycemic control. Considering the potential role of resistin in insulin
      resistance, decrease in resistin levels may contribute to improving insulin
      action with rosiglitazone treatment.

PMID- 15736109
TI  - Carotid artery intima-media thickness and lipid profile in adults with growth
      hormone deficiency after long-term growth hormone replacement.
AB  - To investigate the effects of growth hormone (GH) replacement on carotid artery
      intima-media thickness (IMT) and lipid profile, 29 adults with GH deficiency
      (GHD), mean age 42.5 +/- 10.1 years, were studied and compared with 29 control
      subjects matched for sex, age, body mass index, and smoking habits. Lipid profile
      (total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol,
      low-density lipoprotein cholesterol, apolipoproteins A and B, and lipoprotein),
      serum insulin-like growth factor 1 (IGF-1) levels, and ultrasonography of the
      carotid arteries were performed at baseline and at 6, 12, and 24 months during GH
      therapy on maintenance dose. At baseline, when compared with the control group,
      patients presented increased carotid artery IMT (P < .05) and triglyceride levels
      (P < .001) and lower HDL concentrations (P < .01). In a linear regression
      analysis, age and known mean duration of GHD were correlated with carotid artery
      IMT. After 24 months of GH replacement, a reduction in the mean of carotid artery
      IMT was observed (P < .01). The apolipoprotein B levels decreased significantly
      after the first 3 months of GH treatment (P < .001) and remained stable
      thereafter. Women also presented an increase in HDL cholesterol levels (P < .01).
      No differences were observed in the other lipids measured. Carotid artery IMT at
      baseline was inversely correlated with the change in carotid artery IMT (Delta =
      24 months - baseline), r = 0.63, P < .001. In conclusion, 24 months of GH
      replacement therapy promoted favorable effects on carotid artery IMT and lipid
      profile in patients with GHD. Long-term follow-up studies are required to show
      whether these beneficial effects will result in reduction of morbidity and
      mortality from vascular disease.

PMID- 15736110
TI  - Altered relationship between body fat and plasma adiponectin in end-stage renal
      disease.
AB  - Patients with end-stage renal disease (ESRD) show an inverse association between
      body mass index and risk of death from cardiovascular disease. Paradoxical
      epidemiology may suggest some beneficial effects of body fat in ESRD. Because an
      antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we
      tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less
      atherogenic or that the relationship between body fat and adipocytokines may be
      altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166
      healthy subjects comparable in age and sex. We measured body fat mass by dual
      energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme
      linked immunosorbent assay. The ESRD group showed a significant increase in
      plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy
      subjects. Although sex and fat mass were significant factors correlating with
      plasma adiponectin level in the healthy group, none of these were significantly
      associated with plasma adiponectin in the patients with ESRD. In contrast, leptin
      showed significant relationships with sex and fat mass regardless of the presence
      of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and
      positively with high-density lipoprotein cholesterol in both healthy and ESRD
      groups, suggesting that uremic adiponectin retains its actions in favor of its
      antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and
      the effects of body fat and sex on adiponectin were less significant in the
      patients with ESRD.

PMID- 15736111
TI  - Isotopomer spectral analysis of intermediates of cholesterol synthesis in
      patients with cerebrotendinous xanthomatosis.
AB  - Four patients with cerebrotendinous xanthomatosis (CTX) and 2 healthy controls
      received a constant proximal intraduodenal infusion of 1- 13 C-acetate as a
      stable-isotope-labeled marker of sterol synthesis. One patient was treated with
      pravastatin (20 mg twice daily) and another patient with chenodeoxycholic acid
      (250 mg tid). Every hour, venous blood and duodenal samples were obtained. Stable
      isotope enrichment of neutral and polar sterols in serum and bile was assessed by
      gas chromatography/mass spectrometry. Isotopomer spectral analysis was performed
      on cholesterol, lathosterol, Delta-8-cholesterol, methylsterol, and lanosterol.
      Stable-isotope labeling of cholestanol, bile acids, and bile alcohols was
      analyzed by assessing the change over time of the ratio of M + 3 to M + 0. Eleven
      hours after marker infusion, we found up to 50% newly synthesized lathosterol in
      serum and up to 80% in bile, with similar results for other cholesterol
      precursors. In cholesterol, stable-isotope labeling could be demonstrated in all
      study subjects with a more prominent labeling in bile than in serum. No stable
      isotope labeling was detected in cholestanol. Only minor stable-isotope
      incorporation was detectable in polar sterols in some subjects. Therapy with
      pravastatin did not have any effect on fractional or absolute synthesis rates or
      on the concentrations of cholestanol or cholesterol precursors compared to
      untreated patients with CTX. In contrast, therapy with chenodeoxycholic acid
      markedly lowered the concentrations of cholestanol and cholesterol precursors,
      led to a disappearance of bile alcohols, and reduced absolute synthesis rates of
      lathosterol. Isotopomer spectral analysis proved to be a powerful method to
      assess the endogenous synthesis of cholesterol precursors in patients with CTX.
      Higher fractional synthesis in bile than in serum may be due to the size of the
      pools in bile vs serum. Cholestanol exhibits no marker uptake and is therefore
      probably synthesized from preformed cholesterol. Biliary cholesterol secretion in
      patients with CTX is decreased compared to healthy controls.

PMID- 15736112
TI  - High serum pentosidine concentrations are associated with increased arterial
      stiffness and thickness in patients with type 2 diabetes.
AB  - Accumulation of advanced glycation end products in vessel walls may increase
      arterial stiffness and/or thickness, contributing to a high incidence of
      cardiovascular disease (CVD) in patients with diabetes. We investigated whether
      serum concentrations of pentosidine, a well-defined advanced glycation end
      product, are associated with arterial stiffness or thickness in patients with
      type 2 diabetes. Pentosidine was measured in sera from 98 patients with type 2
      diabetes and 61 age-matched control subjects by a competitive enzyme-linked
      immunosorbent assay. Arterial stiffness was evaluated by heart-brachial and
      brachial-ankle pulse wave velocities (PWVs) measured using an automatic device.
      Arterial thickness was determined ultrasonographically as carotid intima-media
      wall thickness (IMT). Serum concentrations of pentosidine were significantly
      higher in patients with diabetes than in control subjects (64.4 +/- 21.0 vs 22.8
      +/- 7.0 microg/L; P < .0001). In patients with diabetes, serum pentosidine
      correlated positively with heart-brachial PWV (r = 0.304; P < .01) but not with
      brachial-ankle PWV. Serum pentosidine also correlated positively with carotid IMT
      in patients with diabetes (r = 0.300; P < .01). Serum pentosidine concentrations
      were significantly higher in patients with diabetes with CVD than in those
      without (72.3 +/- 23.7 vs 62.3 +/- 19.8 microg/L; P = .0453). By multivariate
      analysis, only age (partial coefficient = 0.308; P < .05) and serum creatinine
      (partial coefficient = 0.328; P < .01) retained significant influence on serum
      pentosidine. After adjustment for renal function, carotid IMT still correlated
      positively with serum pentosidine (partial coefficient = 0.2736; P = .021). In
      conclusion, serum pentosidine was positively associated with both arterial
      stiffness and thickness and CVD in patients with type 2 diabetes.

PMID- 15736113
TI  - Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric
      dimethylarginine, and endothelial function in healthy human subjects during
      experimental hyper- and hypohomocysteinemia.
AB  - Experimental hyperhomocysteinemia after an oral methionine or homocysteine load
      is associated with impaired nitric oxide-dependent vasodilatation in healthy
      human beings. However, it remains unproven that this effect is mediated by
      elevations in plasma homocysteine. There is evidence that an increase in plasma
      homocysteine may increase the formation of asymmetric dimethylarginine (ADMA), an
      inhibitor of nitric oxide synthase. The methyl groups within ADMA are derived
      from the conversion of S -adenosylmethionine to S -adenosylhomocysteine
      intermediates in the methionine/homocysteine pathway. No previous study has
      assessed the role of methylation status, its impact on ADMA formation, and their
      association with endothelial function in healthy human beings. In a randomized,
      placebo-controlled, crossover study, 10 healthy subjects (mean age, 29.1 +/- 3.9
      years) were administered an oral dose of methionine (0.1 g/kg), l -homocysteine
      (0.01 g/kg), N-acetylcysteine (NAC) (0.1 g/kg), or placebo. Endothelial function
      as assessed by flow-mediated dilatation (FMD) of the brachial artery was impaired
      after both the methionine and homocysteine load compared with placebo at 4 hours
      (36 +/- 15, 67 +/- 23 vs 219 +/- 26 microm, respectively, P < .001). N
      Acetylcysteine had no effect on flow-mediated dilatation. Plasma total
      homocysteine was significantly elevated at 4 hours after methionine (23.1 +/-
      6.2) and homocysteine (41.5 +/- 8.9) loading, but significantly reduced after NAC
      2.4 +/- 0.6 vs 7.1 +/- 2.1 micromol/L in the placebo (P < .001). Plasma S
      adenosylmethionine/S-adenosylhomocysteine ratio was significantly (P < .001)
      increased at 4 hours after methionine (10.9 +/- 0.7) compared with homocysteine
      (5.4 +/- 0.4), NAC (5.0 +/- 0.3), and placebo (6.0 +/- 0.5). Plasma ADMA
      concentrations were not altered by any intervention. Our results suggest that
      endothelial dysfunction due to methionine or homocysteine loading is not
      associated with an increase in plasma ADMA or a disruption in methylation status.

PMID- 15736114
TI  - The metabolism of apolipoproteins (a) and B-100 within plasma lipoprotein (a) in
      human beings.
AB  - The metabolism of apolipoproteins (apo) (a) and B-100 within plasma lipoprotein
      (a) [Lp(a)] was examined in the fed state in 23 subjects aged 41 to 79 years who
      received a primed-constant infusion of [5,5,5-2H3] leucine over 15 hours.
      Lipoprotein (a) was isolated from the whole plasma using a lectin affinity-based
      method. Apolipoprotein (a) and apoB-100 were separated by gel electrophoresis,
      and tracer enrichment of each apolipoprotein was measured using gas
      chromatography/mass spectrometry. Data were fit to a multicompartmental model to
      determine fractional catabolic rates (FCRs) and secretion rates (SRs). The FCRs
      of apo(a) and apoB-100 (mean +/- SEM) within plasma Lp(a) were significantly
      different (0.220 +/- 0.030 pool/d and 0.416 +/- 0.040 pool/d, respectively; P <
      .001). Apolipoprotein (a) SR (0.50 +/- 0.08 mg/[kg per d]) was significantly
      lower than that of apoB-100 SR (1.53 +/- 0.22 mg/[kg per d]; P < .001) of Lp(a).
      Plasma concentrations of Lp(a) were correlated significantly with both apo(a) SR
      and apoB-100 SR (r = 0.837 and r = 0.789, respectively; P < .001) and negatively
      with apo(a) FCR and Lp(a) apoB-100 FCR (r = -0.547 and r = -0.717, respectively;
      P < .01). These data implicate different metabolic fates for apo(a) and apoB-100
      within Lp(a) in the fed state. We therefore hypothesize that apo(a) does not
      remain covalently linked to a single apoB-100 lipoprotein but that it rather
      reassociates at least once with another apoB-100 particle, probably newly
      synthesized, during its plasma metabolism.

PMID- 15736116
TI  - Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese
      Japanese type 2 diabetic patients.
AB  - The aim of the present study was to investigate the relationships between insulin
      resistance and soluble E-selectin, body mass index (BMI), leptin, and serum lipid
      profile including triglycerides in nonobese Japanese type 2 diabetic patients. A
      total of 97 nonobese Japanese type 2 diabetic patients aged 43 to 84 years were
      examined. The duration of diabetes was 11.2 +/- 0.8 years. In conjunction with
      BMI and fasting concentrations of plasma glucose, serum lipids (triglycerides,
      total cholesterol, and high-density lipoprotein cholesterol) and serum insulin,
      soluble E-selectin, and leptin were also measured. The low-density lipoprotein
      (LDL) cholesterol level was calculated using the Friedewald formula. Insulin
      resistance was estimated by the homeostasis model assessment. The subjects were
      divided into 2 groups according to the value of insulin resistance estimated by
      the homeostasis model assessment. Values greater than 2.5 were indicative of the
      insulin-resistant state, and values less than 2.5 were indicative of the insulin
      sensitive state. The insulin-resistant group had significantly higher levels of E
      selectin, leptin, triglycerides, total and LDL cholesterol, and diastolic blood
      pressure as compared with the insulin-sensitive group. There was, however, no
      significant difference in age, sex, diabetes duration, BMI, systolic blood
      pressure, HbA1c, and high-density lipoprotein cholesterol between the 2 groups.
      Univariate regression analysis showed that insulin resistance was positively
      correlated to E-selectin (r = 0.305, P = .003), BMI (r = 0.283, P = .006), leptin
      (r = 0.296, P = .004), HbA1c (r = 0.241, P = .018), serum triglycerides (r =
      0.385, P < .001), serum total (r = 0.240, P = .019) and LDL cholesterol (r =
      0.254, P = .013) levels, and systolic (r = 0.247, P = .024) and diastolic (r =
      0.305, P = .006) blood pressure. Multiple regression analyses showed that insulin
      resistance was independently predicted by serum E-selectin (F = 18.4), serum
      leptin (F = 14.0) and serum triglycerides (F = 20.0) levels, which explained
      45.0% of the variability of insulin resistance. From these results, it can be
      concluded that in conjunction with serum triglycerides and serum leptin, serum E
      selectin is another important independent factor associated with insulin
      resistance in nonobese Japanese type 2 diabetic patients.

PMID- 15736115
TI  - Cellular insulin resistance in Epstein-Barr virus-transformed lymphoblasts from
      young insulin-resistant Japanese men.
AB  - The metabolic syndrome is characterized by a blunted insulin-mediated glucose
      uptake in various cell types. We compared the glucose uptake characteristics of
      Epstein-Barr virus (EBV)-transformed lymphoblasts obtained from young men with vs
      without metabolic and cardiovascular evidence of metabolic syndrome. From a
      population of 218 men, 20- to 25-year-old, 10 men with a systolic blood pressure
      (BP) > or =130 mm Hg and family history of hypertension were assigned to a high
      BP (HBP) group, and 10 with a BP < or =110 mm Hg, and no family history of
      hypertension was assigned to a low BP (LBP) group. Multiple clinical and
      metabolic characteristics were examined in both groups and compared. Peripheral
      lymphocytes from HBP and LBP subjects were EBV-transformed, and the glucose
      transporter (Glut)-mediated glucose uptake from each group was compared in
      lymphoblasts. Body mass index, fasting glucose, immunoreactive insulin, insulin
      resistance index based on a homeostasis model assessment (HOMA-R), and total and
      low-density lipoprotein cholesterol were significantly higher in the HBP than the
      LBP subgroup (whole-body insulin resistance). Baseline Glut-mediated and Glut
      mediated insulin-stimulated glucose uptake by lymphoblasts from the HBP group
      were significantly lower than by lymphoblasts from the LBP group (cellular
      insulin resistance). The net increment in Glut-mediated glucose uptake by insulin
      was inversely correlated with HOMA-R. In conclusion, cellular insulin resistance
      in EBV-transformed lymphoblasts is associated with young Japanese subjects with
      HBP. The net increment in Glut-mediated glucose uptake by insulin in lymphoblasts
      may be a useful intermediate phenotype to study genetic aspects of the metabolic
      syndrome.

PMID- 15736117
TI  - The K469E polymorphism of the intercellular adhesion molecule-1 gene is
      associated with plasma fibrinogen level in type 2 diabetes.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and
      development of atherosclerotic change of vascular endothelium. The aim of the
      present study is to investigate whether K469E polymorphism of the ICAM-1 gene is
      associated with various clinical factors including plasma fibrinogen in patients
      with type 2 diabetes. ICAM-1 gene polymorphism was examined using polymerase
      chain reaction and restriction enzyme analysis in 360 type 2 diabetic patients.
      Plasma fibrinogen levels and other clinical variables were measured as well as
      circulating soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay.
      The distribution of ICAM-1 genotypes, EE, EK, and KK, was not significantly
      different between type 2 diabetes and 152 healthy control subjects. Among 3
      groups according to ICAM-1 genotypes in type 2 diabetes, no difference was found
      in adiposity, glycemic control, lipid profile, insulin sensitivity evaluated by
      homeostasis model assessment, or sICAM-1. Regarding fibrinogen, the patients with
      E allele showed significantly lower plasma fibrinogen levels in a dose-dependent
      manner (P = .033). Spearman rank correlation analyses revealed that ICAM-1
      genotype showed significant correlation with plasma fibrinogen level (P < .001).
      In multiple regression analysis, ICAM-1 genotype was independent contribution
      factor of plasma fibrinogen level as well as high-density lipoprotein-cholesterol
      and urinary albumin excretion (R2 = 0.148, P < .001). In conclusion, K469E
      polymorphism of the ICAM-1 gene had impact on plasma fibrinogen level
      independently of other clinical factors in 360 type 2 diabetic patients,
      suggesting that fibrinogen is a candidate which links the ICAM-1 gene
      polymorphism to atherosclerosis.

PMID- 15736118
TI  - Effect of two alpha-glucosidase inhibitors, voglibose and acarbose, on
      postprandial hyperglycemia correlates with subjective abdominal symptoms.
AB  - To assess the possible difference in effectiveness of 2 alpha-glucosidase
      inhibitors, voglibose and acarbose, the relationship between postprandial
      hyperglycemia and subjective abdominal symptoms was investigated. A total of 21
      inpatients with type 2 diabetes were recruited to a single-center, 2-period,
      crossover trial. The subjects were given acarbose (150 mg/d) or voglibose (0.9
      mg/d) under an isocaloric diet, and the postprandial (2 hours) increment in blood
      glucose level, M value which is a marker for fluctuation of blood glucose levels,
      and subjective abdominal symptom score were monitored. There was no significant
      difference between the 2 agents in postprandial increment in blood glucose level,
      M value, and subjective symptom score. When patients were divided according to
      subjective symptoms, however, the sum postprandial glucose increments were
      significantly different according to the agent (P = .03), with favorable efficacy
      in patients in whom the alpha-glucosidase inhibitor caused abdominal symptoms,
      demonstrating a significant interaction (P = .04) between treatment and
      symptomatic grouping. The results demonstrated that 50 mg acarbose and 0.3 mg
      voglibose had similar overall effects on postprandial hyperglycemia as well as
      subjective symptoms, but marked interindividual variation existed. Subjective
      symptoms may be a predictor of the divergent clinical response to each agent.

PMID- 15736119
TI  - Changes in blood pressure and plasma catecholamine levels during prolonged
      hyperinsulinemia.
AB  - Hyperinsulinemia has been shown to induce activation of the sympathetic nervous
      system and vasodilatation. Whether these effects result in changes in blood
      pressure (BP) is discussed controversially. We measured BP and plasma
      catecholamine levels in 30 healthy men during a 60-minute baseline phase and 360
      minute period of insulin infusion. In a double-blind, between-subject comparison,
      insulin was infused at a low rate (1.5 mU insulin/kg per minute) in one half of
      the subjects and at a high rate (15 mU/kg per minute) in the other half.
      Throughout the experiments, blood glucose levels were held constantly within the
      normal range by a simultaneous infusion of glucose. Serum insulin levels
      increased to a plateau of 543 +/- 34 pmol/L during low rate and to 24,029 +/-
      1,595 pmol/L during high rate of insulin infusion. Compared with baseline,
      insulin infusion of either rate significantly increased systolic BP, BP
      amplitude, and heart rate (all P < .05). In comparison with the low rate of
      insulin infusion, the high rate provoked a more pronounced increase in heart rate
      (P < .02) and systolic BP (P < .05) but tended to decrease diastolic BP (P < .08)
      summing up to a distinctly more increased BP amplitude (P < .05). Plasma
      norepinephrine as well as epinephrine levels did not significantly change during
      the low-rate insulin infusion but significantly increased during high-rate
      insulin infusion (both P < .05). By showing a dose-dependent increasing influence
      of insulin on systolic BP and circulating catecholamine levels, the present study
      provides experimental evidence for the notion that hyperinsulinemia contributes
      to the development of hypertension.

PMID- 15736120
TI  - Insulin sensitivity indices of glucose and free fatty acid metabolism in obese
      children and adolescents in relation to serum lipids.
AB  - OBJECTIVE: Most studies concerning the association between insulin resistance and
      the features of metabolic syndrome in obese children are based on measurement of
      insulin sensitivity indices (ISI) of glucose metabolism and not of fat
      metabolism. METHODS: We studied fasting low-density lipoprotein cholesterol (LDL
      C), high-density lipoprotein cholesterol (HDL-C), triglycerides, insulin, free
      fatty acids (FFA), blood glucose, ISI of glucose (homeostasis model assessment
      [HOMA] %S), and FFA metabolism (ISI-FFA) in 124 obese children aged 6 to 16
      years. ISI-FFA was calculated based on the formula 2/(insulin x FFA + 1).
      Stepwise forward regression analyses were performed with triglycerides, HDL-C and
      LDL-C as dependent variables and age, sex, stage of puberty, body mass index,
      insulin, FFA, and blood glucose as independent variables. Direct multiple
      regression analyses were conducted with the dependent variables triglycerides,
      HDL-C, and LDL-C including age, sex, stage of puberty, body mass index, HOMA %S,
      and ISI-FFA as independent variables. Furthermore, ISI-FFA was measured in 13
      normal-weight children aged 6 to 16 years. RESULTS: ISI-FFA (median 0.30) was
      significantly (P < .05) reduced in obese children compared with normal-weight
      children (median ISI-FFA 0.64). In stepwise regression analyses, triglycerides
      were significantly correlated with insulin and FFA (P < .05), LDL-C levels were
      significantly correlated with FFA (P < .05), and HDL-C was related to stage of
      puberty (P < .05), whereas all other variables demonstrated no significant
      associations with triglycerides, LDL-C, and HDL-C levels. In contrast to HOMA %S,
      ISI-FFA was significantly (P < .05) related to triglycerides and LDL-C in direct
      multiple regression analysis. CONCLUSIONS: Insulin resistance in respect to FFA
      metabolism is already detectable in childhood. Insulin sensitivity index of FFA
      metabolism seems to be a better tool for describing insulin resistance in lipid
      metabolism than ISI of glucose metabolism, because FFA and partially insulin but
      not glucose were related to triglycerides and LDL-C.

PMID- 15736122
TI  - Influence of calcium-induced workload transitions and fatty acid supply on
      myocardial substrate selection.
AB  - Because of differences in energy yield and oxygen demand, the selection of
      oxidative fuels is important in the hypoxic or ischemic heart muscle. The aim of
      the present study was to clarify the contradictions observed in the effects of
      workload and fatty acid supply on myocardial fuel preference in isolated perfused
      rat hearts. Nuclear magnetic resonance spectroscopy combined with the
      administration of substrates labeled with the stable isotope carbon 13 and
      isotopomer analysis of glutamate labeling offers an opportunity to simultaneously
      measure metabolic fluxes in pathways feeding into the tricarboxylic acid (TCA)
      cycle. The work output was modulated by changes in extracellular calcium. In the
      presence of 5 mmol/L glucose, 0.5 mmol/L octanoate in the perfusate dominated the
      oxidative metabolism, and workload had little effect on the ratio of glucose to
      fatty acid utilization. This was the case even when the octanoate concentration
      was lowered to 50 micromol/L. The relative rate of replenishment of the TCA cycle
      intermediates was higher at a low workload. The redox state of flavoproteins in
      the intact heart was monitored fluorometrically to obtain an estimate of the
      mitochondrial reduced/oxidized nicotinamide-adenine dinucleotide ratio (NADH/NAD
      ratio) for assessment of the dominant level of regulation of cell respiration,
      and the myoglobin spectrum was simultaneously monitored to evaluate the
      oxygenation status of the myocardium. Commencement of octanoate infusion (50
      micromol/L or 0.5 mmol/L) caused a large but transient reduction of mitochondrial
      NAD and, conversely, its cessation elicited NADH oxidation and rebound reduction.
      During glucose oxidation, an increase in workload led to oxidation of the
      mitochondrial NADH, but this effect was much smaller in the presence of 50
      micromol/L octanoate and absent in the presence of 0.5 mmol/L. This indicates
      that strong control of oxygen consumption during glucose oxidation is exerted in
      the mitochondrial respiratory chain, whereas equal control during fatty acid
      oxidation is exerted within the metabolic pathway upstream from the respiratory
      chain. It is concluded that when a medium-chain fatty acid is available,
      myocardial workload and energy consumption have little influence on fuel
      preference and glucose oxidation remains suppressed.

PMID- 15736121
TI  - Increased diacylglycerol acyltransferase activity is associated with triglyceride
      accumulation in tissues of diet-induced insulin-resistant hyperlipidemic
      hamsters.
AB  - Over-accumulation of triglyceride (TG) in insulin-sensitive tissues is associated
      with the development of insulin resistance. We investigated whether enhanced de
      novo lipogenesis via diacylglycerol acyltransferase (DGAT) may contribute to the
      over-accumulation of TG in various tissues (liver, adipose, muscle, and
      intestine) using 2 well-characterized hyperlipidemic, insulin-resistant hamster
      models. In general, a marked increase in TG accumulation was noted in most
      tissues. Interestingly, the increase in TG accumulation corresponded to an
      increase in microsomal DGAT activity which ranged from 114% to 575% in all of the
      examined tissues (n = 7 per group). To delineate the mechanism for the increase
      in DGAT activity, we measured the expression of DGAT-1 and DGAT-2 messenger RNA
      by relative reverse transcriptase polymerase chain reaction (RT-PCR). In general,
      DGAT gene expression changed with DGAT-1 changing the most in the liver and
      adipose tissue, whereas DGAT-2 showed responses mainly in muscle and intestine.
      The increases in messenger RNA expression were not remarkable (averaging 35%; n =
      4 per group) indicating that posttranscriptional mechanism(s) may play a larger
      role in regulating DGAT activity. In summary, the data suggest that elevated DGAT
      activity/expression and the subsequent increase in de novo lipogenesis could in
      part induce the insulin-resistant state.

PMID- 15736123
TI  - Hormonal regulation of hepatic IGF-I and IGF-II gene expression in the marine
      teleost Sparus aurata.
AB  - The present work aimed to determine whether GnRH potentiates the effect of growth
      hormone (GH) on insulin-like growth factors (IGF-I and IGF-II) hepatic gene
      expression in Sparus aurata liver. Since several hepatic genes were shown to
      underlie direct regulation via the hepatic estrogen receptor, another aim was to
      extend our understanding of direct estrogen effects on liver IGFs gene
      expression. Pre-reproductive sea bream females were treated with GH, GnRH,
      estradiol-17beta, GH plus GnRH, and estradiol-17beta plus GH. After 72 hr, all
      treatment induced an increase of plasma estradiol well correlated with the
      increase of plasma vitellogenin (VTG) levels. IGF-I and IGF-II expression in the
      liver of treated females was determined by semi-quantitative RT-PCR, using beta
      actin as internal standard. The results reported here show that GH significantly
      stimulates hepatic transcription of IGF-I and IGF-II genes. Surprisingly, E2 and
      GnRH treatments decreased both IGF-I and IGF-II mRNA levels. In fishes treated
      with GH plus GnRH, the GnRH contrasted the GH effect: the IGF-I mRNA levels were
      still significantly higher than in controls, while the effect of GH on IGF-II
      gene expression was totally abolished. At the same time, in the combined
      treatment with GH plus E2, the E2 counteracted the stimulatory effect of GH on
      both IGF-I and IGF-II genes expression.

PMID- 15736124
TI  - VAP1, with cystatin C motif, an oocyte protein encoded by a novel ovarian
      specific gene during oogenesis in the common brushtail possum (Trichosurus
      vulpecula).
AB  - In the brushtail possum oocyte, vesicles accumulate in a polarized fashion at the
      vegetal pole and cytoplasm rich in mitochondria and containing the germinal
      vesicle comprise the animal pole. During cleavage to early blastocyst stages,
      animal pole cytoplasm locates to the cells of the embryonic hemisphere
      (pluriblast) and vegetal pole vesicular cytoplasm to cells of the abembryonic
      hemisphere (trophoblast). Previously identified 16 amino acid residues,
      associated with the vesicle-rich cytoplasm were used for molecular cloning and
      characterization of a vesicle associated protein, VAP1. The degenerate primer was
      used in a 3'RACE for vap1 gene cloning. The cDNA encoding VAP1 was 516 bp in
      length with no significant homologies and coded for 172 amino acid residues for
      the mature protein. The N-terminal domain of VAP1 showed a structural homology to
      the cysteine protease inhibitor, Cystatin. Gene expression studies during
      oogenesis revealed that vap1 had an ovary-specific, possibly oocyte-specific
      expression, which occurs during follicle formation and growth and in adult
      ovaries. Recombinant VAP1 fusion protein generated polyclonal antibodies in the
      mouse and in the brushtail possum.

PMID- 15736125
TI  - Chromosomal instability in the cattle clones derived by somatic cell nuclear
      transfer.
AB  - Cytogenetic analysis was performed on peripheral lymphocytes collected from 20
      cattle clones (19 showed no overt phenotypic abnormalities except for high birth
      weight while 1 exhibited left forelimb contracture), the donor cell cultures from
      which they were derived and lymphocytes from six insemination produced control
      cattle. All animals and cell cultures had a modal chromosome number of 60. The
      frequency of abnormal cells for donor cell cultures, clones, and controls was
      6.68+/-0.30%, 5.30+/-5.49%, and 5.08+/-1.04%, respectively, and did not differ
      significantly among the groups. There were, however, two clones derived from
      different donor cell cultures with high incidences of 21.29% and 20.13%, of
      abnormal cells consisting of pseudodiploid (near-diploid), near-triploid and near
      tetraploid, and tetraploid cells. Among these two clones, one had only a few
      endoreduplicated nuclei although further studies are necessary to precisely
      define the cytological origin and nature of the abnormal cells. The clones were
      evaluated at multiple time points for up to 20 months of age and the incidence of
      abnormal lymphocytes remained stable indicating that the chromosomally abnormal
      nuclei found in cloned animals was not a transient event. These results show that
      the majority of phenotypically normal clones have normal chromosomal make up but
      that instability of chromosome number can occur in clones that are phenotypically
      normal. Therefore, cytogenetical evaluation of peripheral lymphocytes and other
      tissues with follow up of the phenotypical consequences of these abnormalities is
      warranted even in phenotypically normal clones.

PMID- 15736127
TI  - Isolation and characterization of glycosaminoglycans from bovine follicular fluid
      and their effect on sperm capacitation.
AB  - The majority of published studies have reported the use of commercial heparin to
      capacitate bovine sperm. However, heparin is not present in the female genital
      tract fluids. In this study, we purified large amounts of glycosaminoglycans
      (GAGs) from bovine follicular fluid (FF), characterized them and determined their
      potential to capacitate sperm. FF-GAGs were isolated by protease digestion, lipid
      extraction, and by different precipitation conditions and then purified by ion
      exchange chromatography. Two GAGs, heparan sulfate and chondroitin sulfate B,
      were present in FF. To determine the capacitation potential of FF-GAGs, bovine
      ejaculated sperm were incubated 5 hr with or without 12 or 24 microg/ml of each
      of the FF-GAG fractions or with heparin (12 microg/ml). The purified FF-GAGs and
      heparin did not stimulate sperm acrosome reaction (AR), but stimulated sperm
      capacitation. Fractions 1 and 2 (heparan sulfate) were more active to promote
      capacitation (stimulated up to 3.2-fold) than fractions 3 and 4 (mostly
      chondroitin sulfate B). Fractions 3 and 4 stimulated capacitation two times more
      than the control (without FF-GAGs or heparin). When the heparan sulfate impurity
      was removed from fractions 3 and 4 by acid hydrolysis, the capacitation-promoting
      activity associated with these fractions did not change significantly. When 24
      microg/ml of fraction 1 or 2 were used, the percentage of sperm capacitation
      observed was similar to the capacitation with 12 microg/ml of heparin. Our
      results also indicated that the FF-GAGs interact strongly with the BSP proteins.
      Therefore, it is concluded that heparan sulfate is the GAG that is the most
      potent capacitating factor present in bovine FF.

PMID- 15736126
TI  - Effects of MAP kinase pathway and other factors on meiosis of Urechis unicinctus
      eggs.
AB  - The eggs of Urechis unicinctus Von Drasche, an echiuroid, are arrested at P-I
      stage in meiosis. The meiosis is reinitiated by fertilization. Immunoblotting
      analysis using anti-ERK2 and anti-phospho-MAPK antibodies revealed a 44 kDa MAP
      kinase species that was constantly expressed in U. unicinctus eggs, quickly
      phosphorylated after fertilization, and dephosphorylated slowly before the
      completion of meiosis I. Phosphorylation of the protein was not depressed by
      protein synthesis inhibitor Cycloheximide (CHX), but was depressed by the MEK1
      inhibitor PD98059. Under PD98059 treatment, polar body extrusion was suppressed
      and the function of centrosome and spindle was abnormal though GVBD was not
      affected, indicating that MAP kinase cascade was important for meiotic division
      of U. unicinctus eggs. Other discovery includes: A23187 and OA could
      parthenogenetically activate U. unicinctus eggs and phosphorylated 44 kDa MAP
      kinase species, indicating that the effect of fertilization on reinitiating
      meiosis and phosphorylation of 44 kDa MAP kinase specie is mediated by raising
      intracellular free calcium and by phosphorylation of some proteins, and that
      phosphotase(s) sensitive to OA is responsible for arresting U. unicinctus eggs in
      prophase I. diC8, an activator of PKC, accelerated the process of U. unicinctus
      egg meiotic division after fertilization and accelerated the dephosphorylation of
      44 kDa MAP kinase specie, which implied that the acceleration effect of PKC on
      meiotic division was mediated by inactivation of MAP kinase cascade. Elevating
      cAMP/PKA level in U. unicinctus eggs had no effect on meiotic division of the
      eggs.

PMID- 15736128
TI  - Effects of polyadenylation inhibition on meiosis progression in relation to the
      polyadenylation status of cyclins A2 and B1 during in vitro maturation of bovine
      oocytes.
AB  - The control of protein synthesis during maturation in oocytes is mainly exerted
      through cytoplasmic polyadenylation of stored mRNAs. We first analyzed the
      polyadenylation status of cyclins A2 and B1 during in vitro maturation (IVM) of
      bovine oocytes, using Rapid Amplification of cDNA Ends-Polyadenylation Technique
      (RACE-PAT). An inconstant elongation of the poly(A) tail was observed for cyclin
      A2 transcripts after maturation, while a constant lengthening was observed for
      cyclin B1, occurring during the first 12 hr of incubation. We then evaluated the
      effects of the polyadenylation inhibitor 3'-deoxyadenosine (3'-dA), on
      polyadenylation and nuclear maturation. The presence of 0.02 mM 3'-dA during the
      whole incubation period or from 6 hr after its beginning completely prevented
      meiosis progression in 100% of the oocytes. Polyadenylation of cyclin B1 was also
      completely prevented when 3'-dA was added at 0 hr, and greatly reduced when added
      at 6 hr. When 3'-dA was added at 12 hr, around metaphase I (MI), 46.9% of the
      oocytes have reached metaphase II (MII, vs. 78.8% in the control group) at 24 hr.
      The use of the same concentration of 3'-deoxyguanosine (3'-dG), that impairs
      transcription but not polyadenylation, did not affect cyclins polyadenylation,
      nor nuclear maturation, whatever was the timing of addition. These results
      suggest that the polyadenylation of cyclin B1 could be related to the first peak
      of activity of MPF, occurring around MI (10-12 hr after the onset of the
      maturation period). They also show that, in our culture conditions, inhibition of
      polyadenylation prevents meiosis progression, especially up to the MI stage,
      while inhibition of transcription does not.

PMID- 15736129
TI  - Six post-implantation lethal knockouts of genes for lipophilic MAPK pathway
      proteins are expressed in preimplantation mouse embryos and trophoblast stem
      cells.
AB  - Mitogen-activated protein kinase (MAPK) signaling pathways play an important role
      in controlling embryonic proliferation and differentiation. It has been
      demonstrated that sequential lipophilic signal transduction mediators that
      participate in the MAPK pathway are null post-implantation lethal. It is not
      clear why the lethality of these null mutants arises after implantation and not
      before. One hypothesis is that the gene product of these post-implantation lethal
      null mutants are not present before implantation in normal embryos and do not
      have function until after implantation. To test this hypothesis, we selected a
      set of lipophilic genes mediating MAPK signal transduction pathways whose null
      mutants result in early peri-implantation or placental lethality. These included
      FRS2alpha, GAB1, GRB2, SOS1, Raf-B, and Raf1. Products of these selected genes
      were detected and their locations and functions indicated by indirect
      immunocytochemistry and Western blotting for proteins and RT-polymerase chain
      reaction (PCR) for mRNA transcription. We report here that all six signal
      mediators are detected at the protein level in preimplantation mouse embryo,
      placental trophoblasts, and in cultured trophoblast stem cells (TSC). Proteins
      are all detected in E3.5 embryos at a time when the first known mitogenic
      intercellular communication has been documented. mRNA transcripts of two post
      implantation null mutant genes are expressed in mouse preimplantation embryos and
      unfertilized eggs. These mRNA transcripts were detected as maternal mRNA in
      unfertilized eggs that could delay the lethality of null mutants. All of the
      proteins were detected in the cytoplasm or in the cell membrane. This study of
      spatial and temporal expression revealed that all of these six null mutants post
      implantation genes in MAPK pathway are expressed and, where tested,
      phosphorylated/activated proteins are detected in the blastocyst. Studies on RNA
      expression using RT-PCR suggest that maternal RNA could play an important role in
      delaying the presence of the lethal phenotype of null mutations.

PMID- 15736130
TI  - Estrogen-induced Akt-1 activity in the lizard (Podarcis s. sicula) testis.
AB  - There are always more evidences indicating that 17beta-estradiol (E2) is to be
      necessary for normal male fertility. Here we report the expression of the most
      ubiquitously expressed member of the akt family of genes, akt1, in the lizard
      (Podarcis s. sicula) testis. We have used a nonmammalian vertebrate model (the
      lizard P. s. sicula) to investigate the regulation of the serine/threonine kinase
      Akt activity, implicated in the control of cell proliferation, survival, and
      metabolism, in the testis during the annual sexual cycle and to study whether E2
      exerts a role in the spermatogenesis through Akt-1 activity. Immunocytochemistry
      analysis show that Akt-1 proteins are present in the spermatogonia (SPG), and
      spermatocytes (SPC), and spermatids (SPT). The annual E2 profile shows a
      progressive increase during the active spermatogenesis (from April to June) and a
      peak in the month of August (spermatogonial mitosis). In parallel, Akt-1
      (molecular weight 60 kDa) are highly phosphorylated during the period of active
      spermatogenesis and in post-refractory period (August) compared with the winter
      stasis (from November to March). Present results demonstrate that E2 treatment
      induces the activation of Akt-1, and this effect is counteracted by the anti
      estrogen ICI 182-780.

PMID- 15736131
TI  - Changes in tyrosine phosphorylation associated with true capacitation and
      capacitation-like state in boar spermatozoa.
AB  - Capacitation is defined as a series of events that render boar sperm competent to
      fertilize, either in vivo or in vitro. Moreover, preliminary stages of
      cryopreservation of spermatozoa involving cooling to 5 degrees C have been shown
      to induce capacitation-like changes in boar spermatozoa. Capacitation of boar
      spermatozoa is accompanied by protein phosphorylation, however the relationship
      between both processes is poorly understood. Capacitation status was assessed by
      chlortetracycline (CTC) staining. Changes in protein tyrosine phosphorylation
      were examined in pre-cleared whole cell lysates using a specific anti
      phosphotyrosine monoclonal antibody. Our results in boar spermatozoa show a
      significant positive correlation between p32 tyrosine phosphorylation levels and
      percentage of capacitated (CTC pattern B) spermatozoa. Moreover, incubation of
      boar spermatozoa with two unrelated tyrosine kinase inhibitors induces a
      significant reduction in the percentages of capacitated and acrosome-reacted (AR)
      boar spermatozoa and a reduction in the p32 tyrosine phosphorylation. In our
      conditions, cooling boar spermatozoa to 5 degrees C and rewarming to 39 degrees C
      in a noncapacitating medium results in similar CTC staining patterns to those
      obtained after incubation of boar sperm for 1 or 4 hr at 39 degrees C in a
      capacitating medium. However, cooled-rewarmed fails to induce an increase in p32
      tyrosine phosphorylation in boar spermatozoa. Moreover, CTC staining patterns of
      cooled-rewarmed spermatozoa do not change after incubation with a tyrosine kinase
      inhibitor. In conclusion, our results show a direct relationship between
      capacitation and tyrosine phosphorylation and suggest that p32 tyrosine
      phosphorylation levels could be used as a marker of the true capacitation changes
      observed in boar spermatozoa. Moreover, our results show that true capacitation
      and capacitation-like changes induced after cooling involve alternative
      intracellular tyrosine phosphorylation pathways in boar spermatozoa.

PMID- 15736132
TI  - Activation of pig oocytes using nitric oxide donors.
AB  - Nitric oxide (NO) plays an important role in intracellular signaling, but its
      role during the activation of mammalian oocytes is little understood. In our
      study, in vitro matured pig oocytes were cultured with NO-donors-S-nitroso-N
      acetylpenicillamine (SNAP) or sodium nitropruside (SNP). These treatments were
      able to induce parthenogenetic activation of pig oocytes matured in vitro. The
      specificity of this effect was confirmed by the activation of oocytes by
      exogenous endothelial nitric oxide synthase (eNOS) microinjected in the oocyte
      with its activator calmodulin. Relatively long exposure (10 hr) is needed for
      activation of pig oocytes with 2.0 mM SNAP. An active NOS is necessary for the NO
      dependent activation of pig oocytes because NOS inhibitors L-NMMA or L-NAME are
      able to inhibit activation of oocytes with NO-donor SNAP. On the basis of our
      data, we conclude that the NO-dependent activating stimulus seems inadequate
      because it did not induce the exocytosis of cortical granules. Also, the cleavage
      of parthenogenetic embryos was very low, and embryos did not develop beyond the
      stage of eight blastomeres.

PMID- 15736133
TI  - Changes in histone modifications during in vitro maturation of porcine oocytes.
AB  - Nuclear core histone modifications influence chromosome structures and functions.
      Recently, the involvement of histone acetylations in the cell memory of gene
      expression has been suggested in mouse oocyte maturation. At present, there is
      little available data on histone modifications in mammalian oocyte maturation. In
      the present study, we examined changes in the acetylation of histone H3 lysines 9
      (H3K9) and 14 (H3K14), and histone H4 lysines 5 (H4K5), 8 (H4K8) and 12 (H4K12),
      and trimethylation of H3K9 during in vitro maturation of porcine oocytes.
      Immunocytochemical analyses revealed that the all of the lysines examined were
      highly acetylated in the germinal vesicle stage, and this level of acetylation
      was maintained until the first prometaphase. In the first metaphase, the lysines
      near the N-terminal end, H3K9 and H4K5, were completely deacetylated. The
      acetylation of the lysines far from the N-terminal end, H3K14, H4K8, and H4K12,
      was markedly decreased but still present. The acetylations were increased
      transiently at the first anaphase and telophase, and then decreased again at the
      second metaphase to the same level as the first metaphase. Since effective
      concentrations of trichostatin A (TSA) to inhibit the deacetylation were
      different in various lysine residues, multiple histone deacetylases (HDACs) were
      suggested to function during meiotic maturation. The trimethylation of H3K9 was
      maintained in a high level throughout maturation. These results suggest that the
      histone acetylation during porcine oocyte maturation is precisely controlled by
      the cell cycle.

PMID- 15736134
TI  - Varied patterns of DNA methylation change between different satellite regions in
      bovine preimplantation development.
AB  - Global reduction of DNA methylation, a part of genome reprogramming processes,
      occurs in a gradual manner until before implantation and is recognized as a
      conserved process in mammals. Here, we reported that in bovine, satellite regions
      exhibited varied patterns of methylation changes when one-cell egg advanced to
      the blastocyst; a maintenance methylation was observed in satellite I sequences,
      a decrease in alpha satellites, and an increase in satellite II regions. Cloned
      embryos exhibited similar changes for DNA methylation in the satellite I and
      alpha. We also observed that the satellite I and alpha sequences were methylated
      more in inner cell mass region of the blastocyst whereas the satellite II showed
      selective demethylation in this region. Together, these findings point that
      individual satellite sequences carry their own methylation patterns under the
      pressure of global demethylation, suggesting that local methylation control
      system acts on the satellite regions in early bovine embryos.

PMID- 15736135
TI  - Effect of epidermal growth factor in preimplantation development of porcine
      cloned embryos.
AB  - In this study, we determined the expression of epidermal growth factor (EGF) and
      its receptor (EGFr) gene, and the effect of exogenous EGF supplementation on
      preimplantation development of porcine somatic cell nuclear transfer (SCNT)
      embryos. In vitro matured gilt oocytes were fertilized with frozen-thawed semen
      in vitro or reconstructed with fetal fibroblasts by SCNT. In Experiment 1, total
      RNA was isolated from oocytes, preimplantation SCNT, or in vitro fertilization
      (IVF) embryos. The expression of EGF and EGFr mRNA was determined using reverse
      transcription-polymerase chain reaction (RT-PCR). In SCNT and IVF embryos, the
      EGF mRNA was detected in oocytes, 2-cell, 4-cell, 8-cell, morulae, and
      blastocysts, while EGFr mRNA was detected in oocytes, 2-cell, morulae, and
      blastocysts. In Experiment 2, SCNT embryos at 1-cell stage were cultured in North
      Carolina State University (NCSU)-23 medium supplemented with different
      concentrations of EGF (0.1, 1, or 10 ng/ml). Supplementing with 10 ng/ml EGF
      improved cleavage rate (82.8% vs. 76.8%, P<0.05), but not the rate of blastocyst
      formation compared to the control. At all concentrations, EGF increased (P<0.05)
      the total cell number in blastocysts (range 50.5-53.7 vs. 43.9). In Experiment 3,
      EGF (10 ng/ml) was added to NCSU-23 medium at the morula stage. The EGF did not
      affect blastocyst formation, total cell number in blastocysts or the ratio of
      inner cell mass (ICM) to total cell number. In conclusion, we demonstrated that
      EGF and EGFr mRNA are expressed in porcine IVF and SCNT preimplantation embryos,
      and that EGF increased the quality of blastocysts by increasing total cell
      numbers in porcine SCNT embryos.

PMID- 15736136
TI  - Molecular cloning and characterization of the macaque sperm associated antigen 9
      (SPAG9): an orthologue of human SPAG9 gene.
AB  - The present study was conducted to isolate macaque proteomic homologue of human
      SPAG9 (EMBL nomenclature human sperm associated antigen 9: hSPAG9; Shankar et
      al., 1998: Biochem Biophys Res Commun 243:561-565) in order to find out whether
      the macaque can provide a suitable model for examining its immunocontraception
      effects. Macaque SPAG9 was cloned and sequenced from the macaque testis cDNA
      library. The macaque cDNA contained open reading frame encoding 712 amino acids.
      A 84.9% and 94% homology between macaque and human SPAG9 was found at protein and
      DNA levels. Northern analysis and RNA in situ hybridization experiments revealed
      testis- and stage-specific expressions of macaque SPAG9 mRNA, mainly confined to
      round spermatid suggesting haploid germ cell expression. Anti-human SPAG9
      antibodies recognized native SPAG9 in macaque sperm extract in Western blotting
      and the acrosomal compartment region of macaque sperm in indirect
      immunofluorescence. Flow cytometry analysis further revealed surface localization
      of macaque SPAG9 in live macaque sperm. The amino acid sequence data for nonhuman
      primate SPAG9 suggest that antibodies generated by vaccinating macaque with
      hSPAG9 will recognize nonhuman primate SPAG9, supporting the testing of SPAG9
      contraceptive vaccine based on hSPAG9 in the nonhuman primate model.

PMID- 15736137
TI  - A comparative study of oxidative DNA damage in mammalian spermatozoa.
AB  - Alkaline gel electrophoresis, pulsed field gel electrophoresis, and quantitative
      PCR analyses (QPCR) of the nuclear (nDNA) and mitochondrial (mtDNA) genomes were
      used to assess DNA integrity in the spermatozoa of three species exposed to
      oxidative stress. In human and murine spermatozoa, the mtDNA was significantly
      more susceptible to H2O2-mediated damage than nDNA. In both eutherian species,
      exposure to 250 microM H2O2 induced around 0.6 lesions/10 kb of mtDNA. The mtDNA
      of human spermatozoa was particularly vulnerable to oxidative stress; 0.25, 1,
      and 5 mM H2O2 inducing DNA damage equivalent to 0.62, 1.34, and 1.42 lesions/10
      kb, respectively. Such results emphasize the diagnostic significance of mtDNA as
      a biomarker of oxidative stress in the male germ line. In contrast, no damage
      could be detected by QPCR in the nDNA of either eutherian species, on exposure to
      H2O2 at doses as high as 5 mM. However, electrophoretic analysis indicated that
      severe oxidative stress could induce detectable nDNA fragmentation in human, but
      not murine spermatozoa. The mtDNA of tammar wallaby spermatozoa was relatively
      resistant to oxidative stress, only exhibiting damage (0.6 lesions/10 kb DNA) on
      exposure to 5 mM H2O2. By contrast, the nDNA of wallaby spermatozoa was
      significantly more susceptible to this oxidant than the other species. Such
      vulnerability is consistent with the lack of disulfide cross-linking in marsupial
      sperm chromatin and suggests that chromatin condensation during epididymal
      maturation may be important in establishing the resistance of these cells to the
      genotoxic effects of reactive oxygen species.

PMID- 15736138
TI  - Fear of diabetes complications.

PMID- 15736139
TI  - Configuration and E/Z interconversion mechanism of O(S)-allyl-S(O)-methyl-N
      (acridin-9-yl) iminothiocarbonate.
AB  - The configuration and dynamic behavior of O-allyl-S-methyl-N-(acridin-9
      yl)iminothiocarbonate (1) and its S-allyl-O-methyl regioisomer (2) were studied
      using quantum chemical calculations and by applying a novel graphical method to
      scatter maps obtained from MD simulations for evaluation of an NOE-weighted
      internuclear distance (r(NOE)). Energy calculations indicated that the Z
      configuration was predominant for each compound and, further, this was supported
      both by the calculated chemical shifts and the r(NOE). Both N-inversion- and
      rotation-type transition-state structures were also calculated for the E/Z
      isomerization process, the results indicating that the preferred interconversion
      mechanism for 1 is N-inversion, but contrastingly, interconversion via rotation
      is equally as probable as N-inversion for 2. This supports the notion that one or
      the other or both pathways can be active and each system needs to be assessed on
      a case-by-case basis.

PMID- 15736140
TI  - 'Objective' determination of coupling constants and conformational equilibria by
      solvent variation: a comment.
AB  - Following the preceding paper, the 'objective' method of Abraham et al. for
      determining the conformational equilibrium between molecules rapidly
      interconverting between a number of different conformers has been re-evaluated.
      The method relies on the acquisition of a sufficient data set of nuclear
      couplings in different solvents to obtain an over-determined system with more
      equations than unknowns. The example considered by Deutsch and Roberts, of 1,2
      dichloro-1-fluoroethane, is re-evaluated here. A simple but mathematically
      rigorous computer scanning process is used to analyse the data set instead of the
      iterative but not mathematically rigorous process used previously and the results
      compared with those of Deutsch and Roberts. It is shown that both treatments give
      similar solutions. However, it is emphasized that in these multi-dimensional
      analyses the probable errors in the derived parameters (in this case the
      conformer couplings) may be much larger than the r.m.s. (observed versus
      calculated) errors and this error analysis is essential for a considered
      appraisal of the method.

PMID- 15736142
TI  - Probabilistic sensitivity analysis for NICE technology assessment: not an
      optional extra.
AB  - Recently the National Institute for Clinical Excellence (NICE) updated its
      methods guidance for technology assessment. One aspect of the new guidance is to
      require the use of probabilistic sensitivity analysis with all cost-effectiveness
      models submitted to the Institute. The purpose of this paper is to place the NICE
      guidance on dealing with uncertainty into a broader context of the requirements
      for decision making; to explain the general approach that was taken in its
      development; and to address each of the issues which have been raised in the
      debate about the role of probabilistic sensitivity analysis in general. The most
      appropriate starting point for developing guidance is to establish what is
      required for decision making. On the basis of these requirements, the methods and
      framework of analysis which can best meet these needs can then be identified. It
      will be argued that the guidance on dealing with uncertainty and, in particular,
      the requirement for probabilistic sensitivity analysis, is justified by the
      requirements of the type of decisions that NICE is asked to make. Given this
      foundation, the main issues and criticisms raised during and after the
      consultation process are reviewed. Finally, some of the methodological challenges
      posed by the need fully to characterise decision uncertainty and to inform the
      research agenda will be identified and discussed.

PMID- 15736141
TI  - Further analogues of plant peptide hormone phytosulfokine-alpha (PSK-alpha) and
      their biological evaluation.
AB  - Phytosulfokine-alpha (PSK-alpha), a sulfated growth factor of structure H
      Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-Gln-OH universally found in both monocotyledons and
      dicotyledons, strongly promotes proliferation of plant cells in culture. In
      studies on the structure/activity relationship of PSK-alpha the synthesis was
      performed of a series of a further 23 analogues modified in position 1, 3 or 4 as
      well as simultaneously in positions 1 and 3 of the peptide chain. Peptides were
      synthesized by the solid phase method according to the Fmoc procedure on a Wang
      resin. Free peptides were released from the resin by 95% TFA in the presence of
      EDT. All peptides were tested by competitive binding assay to the carrot membrane
      using 3H-labelled PSK-alpha according to the test of Matsubayashi et al. Among
      these peptide analogues, [H-Phe(4-Cl)1]-PSK-alpha (IV), [H-Phe(4-I)1]-PSK-alpha
      (VII), and [Phe(4-Cl)3]-PSK-alpha (XI) retained 30% PSK-alpha activity. Analogue
      [Tyr(PO3H2)3]-PSK-alpha (IX) showed 10% of PSK-alpha activity.

PMID- 15736143
TI  - Binding cooperativity of two different Lewis acid groups at the edge of
      ferrocene.
AB  - The binding properties of heteronuclear bidentate Lewis acids, in which an
      organoboron and an organotin moiety are attached adjacent to each other at one of
      the Cp rings of ferrocene, have been studied. Treatment of [1,2
      fc(SnMe2Cl)(BClMe)] (1-Cl) (fc = ferrocenediyl) with one equivalent of pyridine
      or 4-dimethylaminopyridine (DMAP) resulted in diastereoselective complexation of
      boron. Adducts 2 and 3 have been studied by multinuclear NMR, and the
      stereoselectivity of complexation was further confirmed by single crystal X-ray
      diffraction of 2. The importance of cooperative effects that involve an
      intramolecular B-ClSn interaction on the diastereoselectivity is evident from
      comparison with binding studies on the phenyl-substituted analogue [1,2
      fc(SnMe2Cl)(BPhMe)] (1-Ph). Complexation of 1-Ph led to diastereomeric mixtures
      of adducts 4 and 5, respectively, which were identified by multinuclear NMR
      including NOESY experiments. The solid-state structure of one of the
      diastereomers of 5 was confirmed by X-ray crystallography. Facile isomerization
      was found in solution and the barrier of activation was determined by VT NMR
      studies (4: Delta(#)(298) = 54.9+/-0.4 kJ mol(-1); 5: Delta(#)(298) = 70.3+/-0.1
      kJ mol(-1)). Competitive binding of pyridine to 1-Cl and [FcB(Cl)Me] (Fc =
      ferrocenyl) showed that cooperative effects between tin and boron lead to
      significant Lewis acidity enhancement. Binding of a second nucleophile in the
      presence of excess of base occurred also at boron. The novel zwitterionic
      complexes [1,2-fc(BMe(py)2)(SnMe2Cl2)] (6) and [1,2-fc(BMe(dmap)(2))(SnMe(2)Cl2)]
      (7) formed, which consist of boronium cation and stannate anion moieties. The
      structure of 7 in the solid-state was confirmed by X-ray crystallography.
      Multinuclear NMR data and competition experiments indicate weak binding of
      chloride to tin in 7 and partial dissociation in solution.

PMID- 15736144
TI  - Anal intraepithelial neoplasia.
AB  - BACKGROUND: Anal intraepithelial neoplasia (AIN) is believed to be a precursor of
      anal squamous cell cancer and its incidence is rising in high-risk groups,
      particularly those infected with the human immunodeficiency virus (HIV). The
      natural history of AIN is unclear and management strategies are lacking. METHODS:
      This review is based on a literature search (Medline and PubMed) with manual
      cross-referencing of all articles related to AIN. RESULTS AND CONCLUSIONS: The
      aetiology of AIN is intricately linked with human papilloma viruses. The
      pathological processes involved in the progression of AIN are becoming clearer
      but the natural history, particularly the rate of progression to invasive cancer,
      remains unknown. There is no standard management for AIN and this is mainly due
      to difficulties in both diagnosis and treatment. A variety of treatment options
      have been tried with varying success. Surgery is associated with significant
      recurrence, particularly in HIV-positive patients. Non surgical approaches with
      imiquimod, photodynamic therapy and vaccination are appealing, and further work
      is required. Long-term follow-up of these patients is essential until the natural
      history of AIN becomes clearer.

PMID- 15736145
TI  - p-Nitrophenoxycarbonyl derivatives of Boc-protected diaminoalkanes in the
      synthesis of enkephalin peptidomimetics.
AB  - The synthesis of p-nitrophenoxycarbonyl derivatives of 1-Boc-1,2-diaminoethane, 1
      Boc-1,3-diaminopropane and 1-Boc-1,4-diaminobutane is described. These
      derivatives were used to synthesize five peptidomimetics, analogues of
      enkephalin, containing alkylurea units inside the peptide chain and at the C
      terminal. All syntheses were carried out in solid phase on MBHA resin.
      Peptidomimetics with alkylurea units inserted into the peptide chain were
      synthesized using the standard method employing the Boc-strategy, with TFA
      deprotection and HF cleavage. The analogue containing a C-terminal alkylurea unit
      was synthesized using the Boc-strategy, with HCl/dioxane deprotection and TFA
      cleavage. All of the analogues were examined for opioid activity in GPI and MVD
      assays. The activity of the analogue containing a C-terminal alkylurea unit was
      comparable to that of [Leu5]-enkephalin, while the other analogues were less
      active.

PMID- 15736146
TI  - Xenophilic complexes bearing a Tp(R) Ligand, [Tp(R)M--M'Ln] [Tp(R) = Tp(iPr2),
      Tp(#) (Tp(Me2,4-Br)); M=Ni, Co, Fe, Mn; M'Ln = Co(CO)4, Co(CO)3(PPh3),
      RuCp(CO)2]: the two metal centers are held together not by covalent interaction
      but by electrostatic attraction.
AB  - A series of dinuclear complexes, [Tp(R)M--M'L(n)] [Tp(iPr(2) )M--Co(CO)(4) (1;
      M=Ni, Co, Fe, Mn); Tp(#)M--Co(CO)(4) (1'; M=Ni, Co); Tp(#)Ni--RuCp(CO)(2) (3')]
      (Tp(iPr(2) )=hydrotris(3,5-diisopropylpyrazolyl)borato; Tp(#) (Tp(Me(2),4
      Br))=hydrotris(3,5-dimethyl-4-bromopyrazolyl)borato), has been prepared by
      treatment of the cationic complexes [Tp(iPr(2) )M(NCMe)(3)]PF(6) or the halo
      complexes [Tp(#)M--X] with the appropriate metalates. Spectroscopic and
      crystallographic characterization of 1-3' reveals that the tetrahedral, high-spin
      Tp(R)M fragment and the coordinatively saturated carbonyl-metal fragment (M'L(n))
      are connected only by a metal-metal interaction and, thus, the dinuclear
      complexes belong to a unique class of xenophilic complexes. The metal-metal
      interaction in the xenophilic complexes is polarized, as revealed by their nu(CO)
      vibrations and structural features, which fall between those of reference
      complexes: covalently bonded species [R--M'L(n)] and ionic species [M'L(n)](-).
      Unrestricted DFT calculations for the model complexes [Tp(H(2) )Ni--Co(CO)(4)],
      [Tp(H(2) )Ni--Co(CO)(3)(PH(3))], and [Tp(H(2) )Ni--RuCp(CO)(2)] prove that the
      two metal centers are held together not by covalent interactions, but by
      electrostatic attractions. In other words, the obtained xenophilic complexes can
      be regarded as carbonylmetalates, in which the cationic counterpart interacts
      with the metal center rather than the oxygen atom of the carbonyl ligand. The
      xenophilic complexes show divergent reactivity dependent on the properties of
      donor molecules. Hard (N and O donors) and soft donors (P and C donors) attack
      the Tp(R)M part and the ML(n) moiety, respectively. The selectivity has been
      interpreted in terms of the hard-soft theory, and the reactions of the high-spin
      species 1-3' with singlet donor molecules should involve a spin-crossover
      process.

PMID- 15736148
TI  - Double-helical ultrastructure of polycationic dendronized polymers determined by
      single-particle Cryo-TEM.
AB  - The ultrastructure of cationic dendronized polymers (denpols) of third and fourth
      generations (PG3 and PG4) in water was determined by using single-particle cryo
      transmission electron microscopy (cryo-TEM). At concentrations in the region of
      50 mg L(-1), networks of double-stranded fibers were revealed that exhibit well
      defined diameters of 5.9 nm+/-0.4 nm for PG3 and 7.4 nm+/-0.4 nm for PG4. The
      structure varies with progression along the fibers, and includes a double helix
      with a pitch of 7.0+/-0.4 nm for PG3 and 9.0+/-0.4 nm for PG4. The formation of
      the double strands is attributed to the hydrophobic effect and limited crowding
      in the dendron shell of the third and fourth generation denpols investigated.
      From solutions of lower concentrations (around 10 mg L(-1)), isolated molecular
      fibers were adsorbed onto high-energy surfaces and examined by performing
      scanning force microscopy (SFM) on mica, and after staining, TEM on glow
      discharged carbon films. In both cases, characteristic undulations of single
      strands were observed, which are attributed largely to the adsorption process.

PMID- 15736147
TI  - Syntheses of seven-membered rings: ruthenium-catalyzed intramolecular [5+2]
      cycloadditions.
AB  - The Ru-catalyzed intramolecular [5+2] cycloaddition of cyclopropylenynes is
      investigated with respect to the regio- and diastereoselectivity as well as the
      functional group compatibility of the reaction. Evidence for the mechanism as
      occurring through a ruthenacyclopentene intermediate is elucidated from 1) the
      study of the diastereoselectivity of the cycloaddition; 2) the effect of
      variation of substituents on the regioselectivity of cyclopropyl bond cleavage in
      1,2-trans- and 1,2-cis-disubstituted cyclopropanes and 3) examples that clearly
      do not involve ruthenacyclohexene as intermediates as products still incorporate
      the cyclopropyl moiety. The scope and limitations of the Ru-catalyzed
      cycloaddition are discussed and compared with the Rh-catalyzed reaction. The
      potential power of this methodology towards natural product total synthesis is
      demonstrated by the formation of several polycyclic systems with the chosen
      reaction conditions and readily available cyclopropylenyne substrates.

PMID- 15736149
TI  - Stereoselective synthesis of cis-p-menth-8-ene-1,7-diol, cis-p-menthane-1,7-diol,
      and cis-p-menthane-1,7,8-triol.
AB  - The natural products cis-p-menthane-1,7-diol (cis-IV), cis-p-menth-8-ene-1,7-diol
      (cis-I) and cis-p-menthane-1,7,8-triol (cis-II) are obtained starting from the
      corresponding cis-cyanohydrins, cis-2 and cis-7, respectively, by chemical
      transformation of the cyano into the hydroxymethyl group. The key step of the
      synthesis is the very high cis-selectivity (> or = 96 %) of the MeHNL-catalyzed
      HCN addition to 4-alkylcyclohexanones. From 4-isopropylcyclohexanone (1) the
      cyanohydrin cis-2 and from 4-(1-methylvinyl)cyclohexanone (6) the cyanohydrin cis
      7 result almost quantitatively. Regioselective hydroxylation of cis-I affords the
      triol cis-II. X-ray crystal structure determinations of the final products
      confirm their cis-configuration.

PMID- 15736150
TI  - A study of [Co2(alkyne)(binap)(CO)4] complexes (BINAP=(1,1'-binaphthalene)-2,2'
      diylbis(diphenylphosphine)).
AB  - Understanding the interaction of chiral ligands, alkynes, and alkenes with
      cobaltcarbonyl sources is critical to learning more about the mechanism of the
      catalytic, asymmetric Pauson-Khand reaction. We have successfully characterized
      complexes of the type [Co2(alkyne)(binap)(CO)4] (BINAP=(1,1'-binaphthalene)-2,2'
      diylbis(diphenylphosphine)) and shown that diastereomer interconversion occurs
      under Pauson-Khand reaction conditions when alkyne=HC[triple bond]CCO2Me.
      Attempts to isolate [Co2(alkyne)(binap)(CO)x] complexes with coordinated alkenes
      led to the formation of cobaltacyclopentadiene species.

PMID- 15736152
TI  - Effect of bacoside A on membrane-bound ATPases in the brain of rats exposed to
      cigarette smoke.
AB  - Membrane-bound enzymes play a vital role in neuronal function through maintenance
      of membrane potential and impulse propagation. We have evaluated the harmful
      effects of chronic cigarette smoking on membrane-bound ATPases and the protective
      effect of Bacoside A in rat brain. Adult male albino rats were exposed to
      cigarette smoke for a period of 12 weeks and simultaneously administered with
      Bacoside A (the active principle isolated from Bacopa monniera) at a dosage of 10
      mg/kg b.w/day, p.o. The levels of lipid peroxides as marker for evaluating the
      extent of membrane damage, the activities of Na+/K+-ATPase, Ca2+-ATPase and Mg2+
      ATPase, and associated cations sodium (Na+), potassium (K+), calcium (Ca2+), and
      magnesium (Mg2+) were investigated in the brain. Neuronal membrane damage was
      evident from the elevated levels of lipid peroxides and decreased activities of
      membrane-bound enzymes. Disturbances in the electrolyte balance with accumulation
      of Na+ and Ca2+ and depletion of K+ and Mg2+ were also observed. Administration
      of Bacoside A inhibited lipid peroxidation, improved the activities of ATPases,
      and maintained the ionic equilibrium. The results of our study indicate that
      Bacoside A protects the brain from cigarette smoking induced membrane damage.

PMID- 15736151
TI  - ESR investigation of starch gelatinization using novel spin probes.
AB  - The spin probes 1,1,3,3-tetramethylisoindolin-2-yloxyl (TMIO) and the sodium salt
      of its sulfonate, 1,1,3,3-tetramethylisoindolin-2-yloxyl-5-sulfonate (NaTMIOS)
      were used to monitor the microviscosity changes of water during starch
      gelatinization. In cereal starch, which contains mainly A-type polymorphs,
      evidence was found for the amylopectin and amylose regions, the latter undergoing
      a transition at about 55 degrees C and a large increase in the microviscosity on
      cooling. Pea starch contains both A-and B-type polymorphs and this was also found
      to have two domains and the 55 degrees C transition was observed for the amylose
      phase: the less mobile amylopectin showed a reversible decrease in water
      microviscosity on heating.

PMID- 15736153
TI  - Lipid-lowering efficacy of 3,4-di(OH)-phenylpropionic L-leucine in high
      cholesterol fed rats.
AB  - A preliminary study revealed that 3,4-di(OH)-hydrocinnamate (HC), a polyphenolic
      compound, lowered the plasma lipids in high-cholesterol fed rats. Accordingly,
      this study was designed to test the lipid-lowering efficacy of a synthetic
      derivative, 3,4-di(OH)-phenylpropionic (L-leucine) amide (PPLA), in rats fed a
      high-cholesterol (1%, wt/wt) diet. As such, HC or PPLA was given as supplement to
      a high-cholesterol diet for 6 weeks at a dose of 0.137 mmol/100 g diet. The
      supplementation of HC and PPLA significantly lowered the plasma and hepatic
      cholesterol and triglyceride levels compared to the control group. The activities
      of hepatic HMG-CoA reductase (164 +/- 9.12 and 124.74 +/- 17.09 pmol/min/mg
      protein vs. 245.41 +/- 13.01 pmol/min/mg protein, p < 0.05) and ACAT (411.49 +/-
      11.48 and 334.35 +/- 17.68 pmol/min/mg protein vs. 490.41 +/- 16.69 pmol/min/mg
      protein, p < 0.05) were significantly lower in the HC- and PPLA-supplemented
      groups than in the control group. However, PPLA was more effective in inhibiting
      the enzyme activities than HC. The excretion of neutral sterol was significantly
      higher in HC- and PPLA-supplemented groups than in the control group. Therefore,
      these results indicate that PPLA, a leucine-attached version of HC, exhibited a
      similar significant hypocholesterolemic effect to HC in rats fed a high
      cholesterol diet.

PMID- 15736154
TI  - Prevention of naphthalene-induced pulmonary toxicity by glutathione prodrugs:
      roles for glutathione depletion in adduct formation and cell injury.
AB  - Naphthalene is metabolized in the lung and liver to reactive intermediates by
      cytochrome P450 enzymes. These reactive species deplete glutathione, covalently
      bind to proteins, and cause necrosis in Clara cells of the lung. The importance
      of glutathione loss in naphthalene toxicity was investigated by using the
      glutathione prodrugs (glutathione monoethylester or cysteine-glutathione mixed
      disulfide) to maintain glutathione pools during naphthalene exposure. Mice given
      a single intraperitoneal injection of naphthalene (1.5 mmol/kg) were treated with
      either prodrug (2.5 mmol/kg) 30 min later. Both compounds effectively maintained
      glutathione levels and decreased naphthalene-protein adducts in the lung and
      liver. However, cysteine-glutathione mixed disulfide was more effective at
      preventing Clara cell injury. To study the prodrugs in Clara cells without the
      influence of hepatic naphthalene metabolism and circulating glutathione, dose
      response and time-course studies were conducted with intrapulmonary airway
      explant cultures. Only the ester of glutathione raised GSH in vitro; however,
      both compounds limited protein adducts and cell necrosis. In vitro protection was
      not associated with decreased naphthalene metabolism. We conclude that (1)
      glutathione prodrugs can prevent naphthalene toxicity in Clara cells, (2) the
      prodrugs effectively prevent glutathione loss in vivo, and (3) cysteine
      glutathione mixed disulfide prevents naphthalene injury in vitro without raising
      glutathione levels.

PMID- 15736155
TI  - Usefulness of studies on the molecular mechanism of action of herbals/botanicals:
      The case of St. John's wort.
AB  - The use of herbals/botanicals has been gaining wide popularity in recent years in
      the United States as well as in other parts of the world. The mechanism of action
      of most of these herbals/botanicals has not been subjected to thorough scientific
      investigations. St. John's wort (Hypericum perforatum) represents a useful case
      study in this sense. Traditionally, it is used as a natural treatment for
      depression; however, in recent years its molecular mechanism of action has been
      elucidated by a number of laboratories across the world. Such studies have helped
      understand potential interactions of St. John's wort with drugs and other
      xenobiotics. St. John's wort activates a nuclear receptor called pregnane X
      receptor (PXR). PXR is a ligand-activated transcription factor that induces a
      number of xenobiotic-metabolizing enzymes and transporters including cytochrome
      P4503A4 (CYP3A4) in humans. Because CYP3A4 alone metabolizes about 60% of all
      clinically relevant drugs, induction of CYP3A4 may result in the rapid
      elimination of these drugs and a consequent reduction in drug efficacy.
      Ironically, such enzyme-inducing effects may not produce any immediate adverse
      symptomatology in the person taking St. John's wort. Therefore, the case of St.
      John's wort should serve as a good example of the usefulness and importance of
      studies on the mechanism of action of the herbals/botanicals, particularly those
      with widespread use. Scientists, physicians, and other health professionals can
      make use of the knowledge from such studies as an additional risk management
      tool.

PMID- 15736156
TI  - Effects of nickel poisoning on expression pattern of the 72/73 and 94 kDa stress
      proteins in rat organs and in the COS-7, HepG2, and A549 cell lines.
AB  - The present study deals with the effects of Ni on the expression level of three
      stress proteins, namely, the cytosolic HSP72 and HSP73, and the reticulum
      associated GRP94. Experiments were carried out on "Wistar'' female rats daily
      injected with 4 mg NiCl2 per kg body weight for 1, 3, 5, and 10 days. Another set
      of experiments were carried out using cell lines, derived from the monkey kidney
      (COS-7), and from human tumors of the lung (A549) and liver (HepG2). Cells were
      cultured for 4 days in the permanent presence of 100, 200, or 400 microM NiCl2.
      In control rats, stress proteins pattern was found to be tissue specific: two
      protein bands of 96 and 94 kDa were immunodetected with the anti-GRP94 antibody
      in kidney and liver extracts, whereas only the 96 kDa band was present in ovary
      extracts. HSP73 was present in kidney, liver, and ovary whereas HSP72 was only
      found in kidney. In kidney of nickel-treated animals, HSP73 and the 96 kDa
      proteins were overexpressed whereas HSP72 was strongly down regulated. No such
      effect was observed in liver or ovary. Similarly, in nickel-treated cell lines,
      HSP72 was downregulated and GRP94 (96 kDa protein) was overexpressed. HSP73
      expression appeared moderately increased in A549 cells but decreased in COS-7
      cells. Because long-term caloric restriction was reported to reduce free radical
      generation in cells, the effect of 1 month food restriction (50%) was tested in
      rats as a possible way to lower oxidative damages induced by Ni. No significant
      effect on HSP expression was observed.

PMID- 15736157
TI  - Potential neuroprotective effect of t-butylhydroquinone against neurotoxicity
      induced by 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl
      MPTP) in mice.
AB  - Dopaminergic damage inducing Parkinson's disease (PD) is ubiquitous
      neurodegenerative disorder, characterized by the progressive loss of dopaminergic
      neurons in the nigrostriatal pathways. The etiology and pathogenic factors
      implicated in dopaminergic damage are still unexplored to develop causal
      therapeutic strategies aimed to halt its progressive loss. The neurotoxicity
      induced by 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP),
      which is more potent neurotoxic than MPTP in mice, is one of the most valuable
      models for analyzing pathological feature of dopaminergic damage. Herein, we
      investigated the neuroprotective effect of the potent antioxidant tertiary
      butylhydroquinone (TBHQ) against 2'CH3-MPTP-induced neurotoxicity in mice as well
      as the possible mechanism underlying such neurotoxicity. Male albino mice were
      injected with two doses of 2'CH3-MPTP (20 mg/kg, i.p.) for two consecutive days.
      Animals were killed after 2 weeks from the last dose of 2'CH3-MPTP. Control
      animals received 10 mL/kg body weight i.p. of distilled water. In both groups,
      brain stems containing the nigrostriatal pathways were dissected and reduced
      glutathione (GSH), malonyldialdehyde (MDA) contents, and superoxide dismutase
      (SOD) activity were estimated. Also, brain stem histopathological and
      histochemical changes were examined. The results of this study revealed that i.p.
      injection of 2'CH3-MPTP caused decrease in the brain stem content of GSH. On the
      other hand, the content of MDA and SOD activity was increased as compared with
      control groups. Also, 2'CH3-MPTP showed severe histopathological changes
      including swelling of cytoplasm, interstitial edema, and complete loss of the
      neurons with reactive microglial proliferation and gliosis. Furthermore,
      histochemical examination of brain stem qualitatively showed depletion of
      dopaminergic neurons of nigrostriatum. Oral administration of TBHQ (100 mg/kg)
      prior to 2'CH3-MPTP for 7 days caused normalization of GSH content and SOD
      activity and ameliorated the MDA content but still above the control value.
      Pretreatment with TBHQ slightly mitigated the histopathological and histochemical
      changes observed in 2'CH3-MPTP-treated mice. Based on these observations, it can
      be concluded that the antioxidant TBHQ has the ability to reverse the oxidative
      stress caused by 2'CH3-MPTP in mice while failed to challenge the
      histopathological and histochemical changes induced by that toxicant.

PMID- 15736158
TI  - Dichloroacetate-induced developmental toxicity and production of reactive oxygen
      species in zebrafish embryos.
AB  - Dichloroacetate (DCA) is one of the toxic by products that are formed during the
      chlorine disinfection process of drinking water. In this study, the developmental
      toxicity of DCA has been determined in zebrafish (Danio rerio) embryos. Embryos
      were exposed to different concentrations (4, 8, 16, and 32 mM) of the compound at
      the 4 h postfertilization (hpf) stage of development, and were observed for
      different developmental toxic effects at 8, 24, 32, 55, 80, and 144 hpf. Exposure
      of embryos to 8-32 mM of DCA resulted in significant increases in the heart rate
      and blood flow of the 55 and 80 hpf embryos that turned into significant
      decreases at the 144 hpf time point. At 144 hpf, malformations of mouth
      structure, notochord bending, yolk sac edema and behavioral effects including
      perturbed swimming and feeding behaviors were also observed. DCA was also found
      to produce time- and concentration-dependent increases in embryonic levels of
      superoxide anion (O2*-) and nitric oxide (NO), at various stages of development.
      The results of the study suggest that DCA-induced developmental toxic effects in
      zebrafish embryos are associated with production of reactive oxygen species in
      those embryos.

PMID- 15736159
TI  - Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia:
      results of the first US randomized, double-blind, placebo-controlled study.
AB  - Botulinum toxin type A (Dysport) has been shown in European studies to be a safe
      and effective treatment for cervical dystonia. This multicenter, double-blind,
      randomized, controlled trial assessed the safety and efficacy of Dysport in
      cervical dystonia patients in the United States. Eighty patients were randomly
      assigned to receive one treatment with Dysport (500 units) or placebo.
      Participants were followed up for 4 to 20 weeks, until they needed further
      treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after
      treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8,
      and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10
      point vs. 3.8-point reduction in total score, respectively, at week 4; P < or =
      0.013). Of participants in the Dysport group, 38% showed positive treatment
      response, compared to 16% in the placebo group (95% confidence interval, 0.02
      0.41). The median duration of response to Dysport was 18.5 weeks. Side effects
      were generally similar in the two treatment groups; only blurred vision and
      weakness occurred significantly more often with Dysport. No participants in the
      Dysport group converted from negative to positive antibodies after treatment.
      These results confirm previous reports that Dysport (500 units) is safe,
      effective, and well-tolerated in patients with cervical dystonia.

PMID- 15736160
TI  - Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats
      with hexachlorobenzene-induced porphyria.
AB  - Uroporphyrinogen decarboxylase is an essential enzyme in all organisms and
      functions in the heme biosynthetic pathway, catalyzing the decarboxylation of the
      four acetate groups of uroporphyrinogen to form coproporphyrinogen. This work
      examines whether the four sequential decarboxylations occur at the same active
      site, and explores whether hexachlorobenzene-induced porphyria affects the
      behavior of the enzyme. For this purpose, kinetic competition studies were done
      with mixtures of uroporphyrinogen III and pentacarboxyporphyrinogen III. With the
      enzyme from normal rats, a constant velocity was obtained with all the mixtures,
      indicating that uroporphyrinogen and pentacarboxy-porphyrinogen react at the same
      active site, i.e. the first and fourth decarboxylations occur at the same site.
      In contrast, in experiments with enzyme from rats with hexachlorobenzene-induced
      porphyria, the total rate for mixtures was always lower than the reference rate;
      and a curve with a deep minimum was obtained, indicating that the two reactions
      occur at functionally different sites, but with cross-inhibition. This suggests
      that the modifications induced in the enzyme by hexachlorobenzene cause the two
      active sites to become nonequivalent and functionally different. The question is
      discussed how the hexachlorobenzene treatment may produce this abnormal kinetic
      behavior, and alternative hypotheses are considered.

PMID- 15736161
TI  - Improving hexane removal by enhancing fungal development in a microbial
      consortium biofilter.
AB  - The removal of hydrophobic pollutants in biofilters is often limited by gas
      liquid mass transfer to the biotic aqueous phase where biodegradation occurs. It
      has been proposed that the use of fungi may improve their removal efficiency. To
      confirm this, the uptake of hexane vapors was investigated in 2.6-L perlite
      packed biofilters, inoculated with a mixed culture containing bacteria and fungi,
      which were operated under neutral or acid conditions. For a hexane inlet load of
      around 140 g.m-3.h-1, elimination capacities (EC) of 60 and 100 g.m-3.h-1 were
      respectively reached with the neutral and acid systems. Increasing the inlet
      hexane load showed that the maximum EC obtained in the acid biofilter (150 g.m
      3.h-1) was twice greater than in the neutral filter. The addition of bacterial
      inhibitors had no significant effect on EC in the acid system. The biomass in the
      acid biofilter was 187 mg.g-1 (dry perlite) without an important pressure drop
      (26.5 mm of water.m-1reactor). The greater efficiency obtained with the acid
      biofilter can be related to the hydrophobic aerial hyphae which are in direct
      contact with the gas and can absorb the hydrophobic compounds faster than the
      flat bacterial biofilms. Two fungi were isolated from the acid biofilter and were
      identified as Cladosporium and Fusarium spp. Hexane EC of 40 g.m-3.h-1 for
      Cladosporium sp. and 50 g.m-3.h-1 for Fusarium sp. were obtained in short time
      experiments in small biofilters (0.230 L). A biomass content around 30 mg.g-1
      (dry perlite) showed the potential for hexane biofiltration of the strains.

PMID- 15736162
TI  - Amino acid content of recombinant proteins influences the metabolic burden
      response.
AB  - Recombinant protein production in Escherichia coli often results in a dramatic
      cellular stress response best characterized by a decrease in overall cell
      fitness. We determined that the primary sequence (the amino acid sequence) of the
      recombinant protein alone plays an important role in mitigating this response. To
      do so, we created two polypeptides, modeled after the 39-40 amino acid Defensin
      class of proteins, which contained exclusively the five least (PepAA; His, Trp,
      Tyr, Phe, Met), or most (PepCO: Ala, Glu, Gln, Asp, Asn) abundant amino acids in
      E. coli. We determined that overexpression of PepAA resulted in a drastic
      decrease in growth rate compared to overexpression of PepCO, our model Defensin
      protein MGD-1, or the 26 amino acid polypeptide contained within the pET-3d
      vector backbone. We further determined, using Affymetrix E. coli gene chips, that
      differences among the whole-genome transcriptional responses of these model
      systems were best characterized by altered expression of genes whose products are
      involved in translation, transport, or metabolic functions as opposed to stress
      response genes. Based on these results, we confirmed that translation efficiency
      was significantly reduced in cells overexpressing PepAA compared with the other
      model polypeptides evaluated.

PMID- 15736163
TI  - Mathematical model of influenza A virus production in large-scale microcarrier
      culture.
AB  - A mathematical model that describes the replication of influenza A virus in
      animal cells in large-scale microcarrier culture is presented. The virus is
      produced in a two-step process, which begins with the growth of adherent Madin
      Darby canine kidney (MDCK) cells. After several washing steps serum-free virus
      maintenance medium is added, and the cells are infected with equine influenza
      virus (A/Equi 2 (H3N8), Newmarket 1/93). A time-delayed model is considered that
      has three state variables: the number of uninfected cells, infected cells, and
      free virus particles. It is assumed that uninfected cells adsorb the virus added
      at the time of infection. The infection rate is proportional to the number of
      uninfected cells and free virions. Depending on multiplicity of infection (MOI),
      not necessarily all cells are infected by this first step leading to the
      production of free virions. Newly produced viruses can infect the remaining
      uninfected cells in a chain reaction. To follow the time course of virus
      replication, infected cells were stained with fluorescent antibodies.
      Quantitation of influenza viruses by a hemagglutination assay (HA) enabled the
      estimation of the total number of new virions produced, which is relevant for the
      production of inactivated influenza vaccines. It takes about 4-6 h before visibly
      infected cells can be identified on the microcarriers followed by a strong
      increase in HA titers after 15-16 h in the medium. Maximum virus yield Vmax was
      about 1x10(10) virions/mL (2.4 log HA units/100 microL), which corresponds to a
      burst size ratio of about 18,755 virus particles produced per cell. The model
      tracks the time course of uninfected and infected cells as well as virus
      production. It suggests that small variations (<10%) in initial values and
      specific rates do not have a significant influence on Vmax. The main parameters
      relevant for the optimization of virus antigen yields are specific virus
      replication rate and specific cell death rate due to infection. Simulation
      studies indicate that a mathematical model that neglects the delay between virus
      infection and the release of new virions gives similar results with respect to
      overall virus dynamics compared with a time delayed model.

PMID- 15736164
TI  - Physiological response of central metabolism in Escherichia coli to deletion of
      pyruvate oxidase and introduction of heterologous pyruvate carboxylase.
AB  - We studied the physiological response of Escherichia coli central metabolism to
      the expression of heterologous pyruvate carboxylase (PYC) in the presence and
      absence of pyruvate oxidase (POX). These studies were complemented with
      expression analysis of central and intermediary metabolic genes and conventional
      in vitro enzyme assays to evaluate glucose metabolism at steady-state growth
      conditions (chemostats). The absence of POX activity reduced nongrowth-related
      energy metabolism (maintenance coefficient) and increased the maximum specific
      rate of oxygen consumption. The presence of PYC activity (i.e., with POX
      activity) increased the biomass yield coefficient and reduced the maximum
      specific oxygen consumption rate compared to the wildtype. The presence of PYC in
      a poxB mutant resulted in a 42% lower maintenance coefficient and a 42% greater
      biomass yield compared to the wildtype. Providing E. coli with PYC or removing
      POX increased the threshold specific growth rate at which acetate accumulation
      began, with an 80% reduction in acetate accumulation observed at a specific
      growth rate of 0.4 h-1 in the poxB-pyc+ strain. Gene expression analysis suggests
      utilization of energetically less favorable glucose metabolism via glucokinase
      and the Entner-Doudoroff pathway in the absence of functional POX, while the
      upregulation of the phosphotransferase glucose uptake system and several amino
      acid biosynthetic pathways occurs in the presence of PYC. The physiological and
      expression changes resulting from these genetic perturbations demonstrate the
      importance of the pyruvate node in respiration and its impact on acetate overflow
      during aerobic growth.

PMID- 15736165
TI  - TGF-beta induces novel Lef-1 splice variants through a Smad-independent signaling
      pathway.
AB  - The lymphoid enhancer-binding factor (Lef-1) transcription factor is best known
      for the ability to transduce Wnt signals during development and to mediate
      excessive Wnt signaling in certain types of cancer. We recently identified and
      characterized a novel Wnt-like effect of transforming growth factor-beta (TGF
      beta) on beta-catenin, the binding partner of Lef-1. Therefore, we sought to
      determine the effect of TGF-beta on expression of the Lef/T-cell-specific
      transcription factor (TCF) components of the Wnt pathway. We found that TGF-beta
      markedly induced Lef-1 mRNA expression in cell lines originating from fetal lung
      (Mv1Lu) and newborn skin (Balb/MK), tissues that normally express Lef-1 during
      development. Lef-1 induction was temporally related to but independent of TGF
      beta-induced G1 cell cycle arrest. Furthermore, the induction of Lef-1 was
      independent of both new protein synthesis and Smad-mediated signaling. Using TGF
      beta-treated Mv1Lu cells, we identified multiple splice forms of Lef-1, including
      novel variants that lack both exons 2 and 3. We conclude that the induction of
      Lef-1 has permissive effects on the well-characterized TGF-beta signal that
      inhibits c-myc expression and induces a G1 arrest.

PMID- 15736166
TI  - Electrochemical probe for on-chip type flow immunoassay: immunoglobulin G labeled
      with ferrocenecarboaldehyde.
AB  - Labeling of ferrocenecarboaldehyde (Fc-CHO) to immunoglobulin G (IgG) via
      formation of Schiff-base and its reduction was investigated for construction of
      an electrochemical probe for miniaturized amperometric flow immunoassay.
      Approximately eight molecules of Fc-CHO were labeled to IgG and the reversible
      redox property of ferrocene was observed. Labeling efficiency improved by over
      three times as compared to the conventional method using ferrocenemonocarboxylic
      acid (Fc-COOH). Also, binding affinity of IgG labeled with Fc-CHO to its antigen,
      IgE, was investigated by enzyme-linked immunosorbent assay (ELISA) and surface
      plasmon resonance assay. IgG labeled with Fc-CHO that retained eight ferrocene
      moiety showed sufficient binding affinity to its antigen and the current response
      obtained in the flow electrochemical detection system increased by 14-fold as
      compared with IgG labeled with Fc-COOH when applying the potential of 390 mV vs.
      Ag/AgCl. The minimum detectable concentration of IgG labeled with Fc-CHO was 0.06
      microM. IgG labeled with Fc-CHO demonstrate biochemical and electrochemical
      properties that are useful for electrochemical immunosensors.

PMID- 15736167
TI  - Retinoic acid down-regulates Tbx1 expression in vivo and in vitro.
AB  - Both Tbx1 and retinoic acid (RA) are key players in embryonic pharyngeal
      development; loss of Tbx1 produces DiGeorge syndrome-like phenotypes in mouse
      models as does disruption of retinoic acid homeostasis. We have demonstrated that
      perturbation of retinoic acid levels in the avian embryo produces altered Tbx1
      expression. In vitamin A-deficient quails, which lack endogenous retinoic acid,
      Tbx1 expression patterns were disrupted early in development and expression was
      subsequently lost in all tissues. "Gain-of-function" experiments where RA-soaked
      beads were grafted into the pharyngeal region produced localized down-regulation
      of Tbx1 expression. In these embryos, analysis of Shh and Foxa2, upstream control
      factors for Tbx1, suggested that the effect of RA was independent of this
      regulatory pathway. Real-time polymerase chain reaction analysis of retinoic acid
      treated P19 cells showed a dose-dependent repression of Tbx1 by retinoic acid.
      Repression of Tbx1 transcript levels was first evident after 8-12 hr in culture
      in the presence of retinoic acid, and to achieve the highest levels of
      repression, de novo protein synthesis was required.

PMID- 15736168
TI  - The MLC1v gene provides a transgenic marker of myocardium formation within
      developing chambers of the Xenopus heart.
AB  - Many details of cardiac chamber morphogenesis could be revealed if muscle fiber
      development could be visualized directly within the hearts of living vertebrate
      embryos. To achieve this end, we have used the active promoter of the MLC1v gene
      to drive expression of green fluorescent protein (GFP) in the developing tadpole
      heart. By using a line of Xenopus laevis frogs transgenic for the MLC1v-EGFP
      reporter, we have observed regionalized patterns of muscle formation within the
      ventricular chamber and maturation of the atrial chambers, from the onset of
      chamber formation through to the adult frog. In f1 generation MLC1v-EGFP animals,
      promoter activity is first detected within the looping heart tube and delineates
      the forming ventricular chamber and proximal outflow tract throughout their
      development. The 8-kb MLC1v promoter faithfully reproduces the embryonic
      expression of the endogenous MLC1v mRNA. At later larval stages, weak patches of
      EGFP fluorescence are found on the atrial side of the atrioventricular boundary.
      Subsequently, an extensive lattice of MLC1v-expressing fibers extend across the
      mature atrial chambers of adult frog hearts and the transgene reveals the
      differing arrangement of muscle fibers in chamber versus outflow myocardium. The
      complete activity of the promoter resides within the proximal 4.5 kb of the MLC1v
      DNA fragment, whereas key elements regulating chamber-specific expression are
      present in the proximal-most 1.5 kb. Finally, we demonstrate how cardiac and
      craniofacial muscle expression of the MLC1v promoter can be used to diagnose
      mutant phenotypes in living embryos, using the injection of RNA encoding a Tbx1
      engrailed repressor-fusion protein as an example.

PMID- 15736169
TI  - Promoter activity of the retinoic acid receptor gene in the Ciona intestinalis
      embryo.
AB  - Retinoic acid regulates development of many chordate-specific characteristics.
      The genes encoding retinoic acid receptors (RARs) were isolated only from
      chordates. In the present study, a genomic DNA fragment containing the promoter
      region of the RAR gene (Ci-RAR) in the protochordate Ciona intestinalis was
      isolated. The transgene containing 1,326 bp of the Ci-RAR 5' flanking region was
      expressed in the epidermis, central nervous system, and muscle. The sequence
      element necessary for expression in the epidermis seemed to be subdivided into
      two elements. One was required for activation in the dorsal midline epidermis and
      the other for the rest of the epidermis. The element responsible for activation
      in the central nervous system was characterized by putative binding sites for
      Fox, Ets, and GATA transcription factors. An E-box sequence was required for the
      transgene expression in the tail muscle cells.

PMID- 15736170
TI  - Chicken genome: new tools and concepts.
AB  - Last spring, the Second International Chicken Genome Workshop was held at the
      Stowers Institute for Medical Research, less than 2 months after the first draft
      of the chicken genome was publicly released in March, 2004. This major event was
      highly anticipated by the chicken community, because of the invaluable resources
      that would be newly provided. In addition, from an evolutionary standpoint, birds
      are the species most closely related to mammals, whose genome has been sequenced.
      The meeting gathered both agricultural and academic chicken communities and
      provided the opportunity to discuss the status of the chicken genome sequencing,
      the preliminary analysis of the chicken genome sequences freshly available, and
      the impact on avian genetic tools.

PMID- 15736171
TI  - Effective enantiodifferentiation of spirochalcogenuranes by the dirhodium method:
      towards the determination of absolute configurations?
AB  - The properties of chiral spirochalcogenuranes acting as ligands in adducts with a
      chiral dirhodium tetracarboxylate complex is explored, and the individual adduct
      species are characterized by low-temperature NMR spectroscopy. Chiral recognition
      and the determination of enantiomeric composition of the chiral
      spirochalcogenuranes is easy by evaluating NMR signal dispersions both at low and
      at room- or slightly elevated temperatures. The uniformity in the signs of 1H
      dispersion effects and taking reference to the spiroselenurane with known
      absolute configuration [(S)-(-)-2] indicates that a convenient rule for the
      determination of absolute configuration in the spirochalcogenurane system can be
      established on the basis of 1H chemical shift dispersions.

PMID- 15736172
TI  - Supramolecular photochirogenesis in sensitizing chiral nanopore:
      enantiodifferentiating photoisomerization of (Z)-cyclooctene included and
      sensitized by POST-1.
AB  - By using homochiral mesoporous POST-1 (Scheme 1) as an inherently chiral
      sensitizing host, supramolecular enantiodifferentiating photoisomerizations of
      (Z)-cyclooctene (1Z) were performed for the first time to examine the sensitizing
      ability of the chiral nanopores, walls of which are decorated with pyridine
      chromophore. The homochiral nanopores of POST-1 crystals were demonstrated to
      function as an effective chiral-sensitizing cavity to give the optically active
      (E)-isomer 1E in up to 5% enantiomeric excess (ee), thus expanding the scope of
      porous material-mediated chirogenesis to both ground and excited electronic
      states.

PMID- 15736173
TI  - Analysis of chiral pharmaceuticals using HPLC with CD detection.
AB  - Recent American Food and Drug Administration guidelines have effectively
      determined that mixtures of chiral compounds can no longer be brought to the
      pharmaceuticals marketplace. These guidelines require a means for chiral
      detection and compound separation. This article describes separation and
      detection of chiral pharmaceuticals using HPLC with circular dichroism detection.
      Two over-the-counter (OTC) medications, Prilosec and naproxen sodium, along with
      the prescription drugs Naproxen, Nexium, and Coumadin were analyzed using HPLC
      with CD, UV, and optical rotation (OR) detection. In all cases the CD and UV
      detectors displayed a much greater sensitivity than the OR detector. Although in
      many cases the UV detector did have a slightly better sensitivity than the CD
      detector, the CD detector had the advantage of only responding to the chiral
      compounds, eliminating the possibility of interference with the peaks of
      interest.

PMID- 15736174
TI  - Biological chiral recognition: the substrate's perspective.
AB  - A novel stereocenter-recognition (SR) model has been proposed recently for
      describing the stereoselectivity of biological and other macromolecules towards
      substrates that have multiple stereocenters, based on the topology of substrate
      stereocenters (Sundaresan and Abrol, Prot Sci 11:1330-1339, 2002). The SR model
      provides the minimum number of substrate locations interacting with receptor
      sites that need to be considered for understanding stereoselectivity
      characteristics. Interactions between substrate locations and receptor sites may
      be binding, nonbinding or repulsive in nature and may occur in a many-to-one or
      one-to-many fashion, but for a receptor to be stereoselective, its interactions
      with substrate stereoisomers have to involve a minimum number of locations, in
      the correct geometry. The SR model is topologically rigorous, explains several
      previous experimental observations, and is predictive in nature. It predicts that
      stereoselectivity towards a substrate with N stereocenters in a linear structure
      involves a minimum of N + 2 substrate locations, distributed over all
      stereocenters in the substrate, such that effectively at least three locations
      per stereocenter interact with one or more receptor sites. This article uses the
      SR model to provide an insight into the chiral recognition process from a
      substrate's perspective that is intuitive and simple, furnishing a rigorous
      stereochemical basis for explaining stereoselectivity characteristics of many
      biological systems.

PMID- 15736175
TI  - Relationship between axial length of the emmetropic eye and the age, body height,
      and body weight of schoolchildren.
AB  - This report assesses the relationship of axial length of emmetropic (without
      refractive error) eyes to age, height, and weight in 1,600 Croatian
      schoolchildren. Axial eye lengths were determined by an ultrasonic eye biometry
      (A scan). Axial length of both eyes increases with age, height, and weight but
      shows a closer correlation to height and weight than to age. Boys have a
      significantly longer axial eye length than girls (P < 0.01). Boys or girls of
      similar or nearing body height and body weight and with emmetropic eyes have
      close linear measures of anatomic eye structures within their sex, regardless
      their age. Body height demonstrates the closest correlation to the growth and
      development of the emmetropic eye.

PMID- 15736177
TI  - Issues in evolutionary medicine.
AB  - This paper illustrates the utility of applying evolutionary thought to medical
      issues with three examples: selection arenas, aging, and tradeoffs. First, the
      human female reproductive tract functions as a selection arena at two levels: in
      the ovaries, where atresia reduces the number of oocytes by more than 99.99%
      before any are ovulated, and in the uterus, where early embryos homozygous for
      immune genes are spontaneously aborted. These selective filters early in life
      have implications both for eugenics and for the anti-abortion movement. Second,
      the evolutionary theory of aging predicts that intrinsic mortality should reflect
      extrinsic mortality: if life for adults is risky, then it does not pay to invest
      in maintenance at the expense of reproduction. This idea is well confirmed, at
      least in populations where density effects are not important. While only
      organisms that reproduce asymmetrically should age, even bacteria reproduce
      asymmetrically, and they do age, suggesting that all organisms reproduce
      asymmetrically and therefore age. Third, tradeoffs are central to theories of
      phenotypic design, but the mechanisms that cause them remain obscure. A method is
      suggested to get at the mechanisms of tradeoffs by examining conflicts among
      functions over gene expression. It could be applied in humans to the tradeoff
      between reproductive performance and disease resistance.

PMID- 15736176
TI  - Growth patterns of the heart and kidney suggest inter-organ collaboration in
      facultative fetal growth.
AB  - Maternal smoking during pregnancy has been associated with a number of negative
      sequelae among offspring, including elevated postnatal blood pressure. While
      animal studies have described organ level alterations with smoke exposure, human
      data have been more limited. Thirty-four healthy maternal/fetal pairs (24
      nonsmokers, 10 smokers) participated in a longitudinal growth study from the
      thirteenth week of pregnancy to document fetal kidney and heart growth
      trajectories and morphology. Curve fitting followed by a mixed model for repeated
      measures identified significantly different growth patterns in kidney width,
      thickness, length, and volume growth with exposure: the smoke-exposed fetal
      kidney was wide and thick compared to the unexposed kidney during the second and
      early third trimester, declining to proportionately thin kidneys for length and
      width subsequently. Cardiac growth in width and volume followed a reverse
      pattern: a surge in cardiac volume occurred after 30 weeks with acceleration in
      cardiac width, resulting in a heart that was wide for length and for fetal
      weight. Smoke exposure altered fetal growth in size and timing of the heart and
      kidneys during midgestation, with changes in organ morphology suggesting
      compensatory growth. These are the first data providing anatomical evidence of
      altered renal/cardiac volume relationships that may provide a mechanism to
      previously reported sequelae of in utero smoke exposure. They suggest that cell
      level adaptive responses to hypoxia and/or chemical insults are operative and
      illustrate the importance of longitudinal ultrasound to directly assess the organ
      level growth response of the human fetus to a prenatal stress, in lieu of relying
      on birth outcome measures.

PMID- 15736178
TI  - A brief history of the Human Biology Association: 1974-2004.
AB  - Originally incorporated as the Human Biology Council in 1974, the Human Biology
      Association, as it has been known since 1994, has matured in the intervening 30
      years to become a society that represents broadly the interests of human
      biologists in the U.S. and throughout the world. The purpose of this paper is to
      trace the development of the Association from its foundation to the present in
      the context of changes in the organization of the Association and in its By-Laws,
      officers, committees, and membership; the history of the two journals that served
      as the Association's official organs (Human Biology and American Journal of Human
      Biology); and how the annual meetings have evolved from a modest one-day plenary
      session to meetings that last more than two days and include a variety of
      scientific contributions. Highlights of the national meetings include the Raymond
      Pearl Memorial Lecture, the Franz Boas Distinguished Achievement Award, and the
      Edward E. Hunt, Jr. Student Prize.

PMID- 15736179
TI  - Skin pigmentation, self-perceived color, and arterial blood pressure in Puerto
      Rico.
AB  - Darker skin color has been associated with higher average blood pressure in
      several African-derived populations in the Americas. This pattern has been
      interpreted as evidence of genetic, physiologic, or sociocultural mechanisms, but
      existing evidence does not provide an adequate means of evaluating these
      alternatives. This paper introduces a measurement strategy to isolate the
      cultural and biological dimensions of skin color, and it develops a specific
      hypothesis regarding the cultural significance of skin color in Puerto Rico and
      its relationship to arterial blood pressure. Data come from a face-to-face survey
      in southeastern Puerto Rico (N = 100). There is no association between blood
      pressure and skin pigmentation, as measured by reflectance spectrophotometry.
      However, the discrepancy between self-perceived color and skin pigmentation, a
      measure we call "color incongruity," is associated with systolic blood pressure
      (SBP) through an interaction with socioeconomic status (SES) (P = 0.009). For low
      SES respondents, darker self-ratings of color relative to skin pigmentation are
      associated with higher mean SBP. For high-SES respondents, however, darker self
      ratings of color relative to pigmentation are associated with lower mean SBP. We
      interpret this pattern as evidence that the relationship between skin color and
      blood pressure is mediated by sociocultural processes, and we highlight the need
      for testable hypotheses and appropriate measurement operations in research on
      racial inequalities in health.

PMID- 15736181
TI  - Increased nuchal translucency and distended jugular lymphatic sacs on first
      trimester ultrasound.
AB  - OBJECTIVE: To investigate the presence and volume of jugular lymphatic sacs (JLS)
      in first-trimester fetuses with normal nuchal translucency thickness (NT) and in
      those with increased NT. METHODS: This was a prospective study of 26 fetuses with
      NT > 95(th) percentile, which were compared with 137 fetuses with normal NT.
      Following crown-rump length (CRL) and NT measurement the neck region of the fetus
      was studied by transvaginal ultrasound. The JLS presented as spheroidal
      translusencies in the anterolateral region of the neck. RESULTS: The prevalence
      of JLS differed significantly between fetuses with enlarged NT and the control
      group (P < 0.0001). In the group of 26 fetuses with increased NT, 22 had clearly
      visible JLS. Chorionic villus sampling revealed aneuploidy in 10 and euploidy in
      16 fetuses. In the control group two fetuses, with NT values of 2.8 mm and 2.9
      mm, had JLS; pregnancy outcome was normal in both cases. Logistic regression
      analysis in the total study group showed that an increase in NT was associated
      with a greater probability of JLS being present (for NT = 3-3.5 mm, probability =
      0.67; for NT > 3.5 mm, probability = 0.93). In fetuses with JLS, an increase in
      CRL was associated with a significant increase in right JLS volume (r = 0.51; P
      value = 0.01) and a non-significant increase in left sac volume (r = 0.40; P
      value = 0.09). Increase in NT was not associated with a significant increase in
      JLS volume. CONCLUSION: There is a significant association between increased NT
      and the presence of JLS on first-trimester ultrasound. In our opinion, the
      pathophysiological explanation for increased NT lies in a disturbance in
      lymphangiogenesis.

PMID- 15736180
TI  - Serum leptin levels in Ache Amerindian females with normal adiposity are not
      significantly different from American anorexia nervosa patients.
AB  - Serum leptin, a polypeptide hormone secreted primarily by adipocytes, is a
      reflection of somatic fat availability in humans and other vertebrates. Among
      Ache Amerindians, leptin levels are very low in contrast to other populations,
      despite comparable adiposity with individuals exhibiting much higher leptin
      levels. In order to gain a greater understanding of these differences, leptin
      levels were compared between Ache Amerindian females (n = 12, mean age = 32.2 +/-
      14.0 SD), American females diagnosed with anorexia nervosa (n = 22, mean age =
      23.0 +/- 4.0), and non-anorectic American controls (n = 23, mean age = 23.0 +/-
      4.0). Ache leptin (5.6 +/- 3.2 ng/ml) was not significantly different from
      anorectic patients (5.6 +/- 3.7 ng/ml; P > 0.98) despite greater adiposity (Ache
      33.3% +/- 4.4% vs. anorectic 7.0% +/- 2.0%; P < 0.0001). Ache adiposity was also
      higher than American controls (leptin 19.1 +/- 8.1 ng/ml; fat 28% +/- 5.0%; P <
      0.004) underscoring the uniqueness of Ache leptin profiles. This suggests a
      greater range of population variation in leptin physiology than previously
      suspected and intimates the potential role of chronic environmental conditions.

PMID- 15736182
TI  - Basal metabolic rate in the Yakut (Sakha) of Siberia.
AB  - Human indigenous circumpolar populations have elevated basal metabolic rates
      (BMRs) relative to predicted values; this metabolic elevation has been postulated
      to be a physiological adaptation to chronic and severe cold stress. The present
      study examines BMR in the Yakut, an indigenous high-latitude population from the
      Sakha Republic of Russia to determine (1) whether the Yakut show evidence of an
      elevated BMR, (2) if the Yakut display evidence of age-related changes in BMR,
      and (3) whether lifestyle differences influence BMR. BMR was measured during the
      late summer in 75 women and 50 men (ages 18-56 years) from the Siberian village
      of Berdygestiakh. Measured BMR (+/- SEM) of the entire sample was significantly
      elevated (+6.5%) compared to predictions based on body mass (6,623.7 +/- 94.9 vs.
      6,218.2 +/- 84.7 kJ/day; P < 0.001). Additionally, measured BMR for the entire
      sample was significantly higher than predictions based on fat-free mass (+20.8%)
      and surface area (+8.9%). Males and females both showed significant elevations
      relative to all three standards. The elevated BMR of the Yakut does not appear to
      be attributable to extreme levels of protein, since the Yakut consume a mixed
      diet with a substantial proportion of carbohydrates. No significant age-related
      changes in BMR were found when controlled for body composition. No significant
      relationship was found between lifestyle variables and BMR, suggesting the
      possibility of a genetic or developmental mechanism. This study provides
      additional evidence of metabolic elevation in indigenous circumpolar groups and
      has important implications for estimating the nutritional requirements of these
      populations.

PMID- 15736183
TI  - Nuchal translucency in pregnancies conceived after assisted reproduction
      technology.
AB  - OBJECTIVES: Levels of maternal serum markers of fetal Down syndrome in
      pregnancies conceived after assisted reproduction are different from those of
      normal spontaneous pregnancies. The present study examined the effects of
      conventional in-vitro fertilization (IVF), intracytoplasmic sperm injection
      (ICSI) and embryo cryopreservation on nuchal translucency (NT) thickness.
      METHODS: A retrospective analysis on 16 673 spontaneous pregnancies, 119
      pregnancies with fresh embryos from IVF, 62 pregnancies with frozen-thawed
      embryos from IVF, 81 pregnancies with fresh embryos from ICSI and 39 frozen
      thawed embryos from ICSI was performed. All were singletons with known normal
      outcomes. Multiples of the median (MoM) of NT were compared. RESULTS: The median
      NT MoM of spontaneous pregnancies was 1.01. In the assisted reproduction
      pregnancies, the median NT MoM were significantly increased to 1.07 (P = 0.003),
      1.09 (P = 0.009) and 1.09 (P = 0.001) in pregnancies conceived with fresh embryos
      from IVF, frozen-thawed embryos from IVF and fresh embryos from ICSI,
      respectively. A non-significant increase in median NT MoM (1.04; P = 0.489) was
      also observed in pregnancies with frozen-thawed embryos from ICSI. CONCLUSIONS:
      Increased NT in assisted reproduction pregnancies is postulated to be due to some
      delay in fetal development. Another possible reason might be related to adverse
      antenatal course in these pregnancies.

PMID- 15736184
TI  - Three-dimensional sonography in the evaluation and management of fetal goiter.

PMID- 15736185
TI  - Improved first-trimester Down syndrome screening performance by lowering the
      false-positive rate: a prospective study of 9941 low-risk women.
AB  - OBJECTIVE: To determine the performance of screening for Down syndrome (DS) and
      other major chromosomal abnormalities using nuchal translucency (NT), free beta
      human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A
      (PAPP-A) in a prospective study of a non-selected population. METHODS: Of 9941
      women with an early ultrasound examination, NT was measured in 8622 singleton
      pregnancies with a gestational age between 10 + 3 and 13 + 6 weeks. beta-hCG and
      PAPP-A were analyzed in 6441 cases. Detection rates (DR) and false-positive rates
      (FPR) for the NT screening, the double test (beta-hCG and PAPP-A) and the
      combined test (NT and the double test) were calculated using a 1 : 250 cut-off.
      RESULTS: NT could be measured in 97.5% of cases. The DR for DS with NT screening
      alone was 75% with a FPR of only 1.8%. The double test detected 73% and the
      combined test 91%, for FPRs of 8.8% and 2.1%, respectively. We detected 80% of
      fetuses with other major chromosomal abnormalities with a combination of NT
      screening and other ultrasound findings. Low beta-hCG and PAPP-A values (below
      0.4 MoM) were observed in 0.5% of the women including all cases of triploidy and
      trisomy 18 and 13. CONCLUSIONS: The performance of a screening strategy for DS
      using a combination of NT and the double test was superior to that using either
      NT or the double test alone due to a very low FPR and a higher DR.

PMID- 15736186
TI  - Multicenter study of first-trimester screening for trisomy 21 in 75 821
      pregnancies: results and estimation of the potential impact of individual risk
      orientated two-stage first-trimester screening.
AB  - OBJECTIVES: To evaluate the performance of first-trimester screening for trisomy
      21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal
      serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated
      plasma protein-A (PAPP-A). In addition, the potential impact of a new individual
      risk-orientated two-stage approach to first-trimester screening was examined.
      METHODS: First-trimester combined screening for trisomy 21 was carried out in 75
      821 singleton pregnancies with live fetuses at 11 + 0 to 13 + 6 gestational
      weeks. The detection and false-positive rates for different risk cut-offs were
      calculated. To examine the potential impact of an individual risk-orientated two
      stage approach to first-trimester screening it was assumed that, after first
      trimester combined screening, chorionic villus sampling (CVS) would be performed
      in all patients with a risk estimate of 1 in 100 or more and in none of those
      with a risk estimate of less than 1 in 1000. Those in the intermediate-risk
      category, with a risk estimate of between 1 in 101 and 1 in 1000, would have
      further assessment of risk by first-trimester ultrasound examination to determine
      presence/absence of the nasal bone, presence/absence of tricuspid regurgitation
      or normal/abnormal Doppler velocity waveform in the ductus venosus, and CVS would
      be performed if their adjusted risk became 1 in 100 or more. RESULTS: Fetal NT
      and maternal serum free beta-hCG and PAPP-A were successfully measured in all
      cases. The median maternal age was 31 (range, 13-49) years, the median gestation
      at screening was 12 (range, 11 + 0 to 13 + 6) weeks and the median fetal crown
      rump length was 62 (range, 45-84) mm. Chromosomal abnormalities were identified
      in 544 pregnancies, including 325 cases of trisomy 21. The estimated risk for
      trisomy 21 was 1 in 300 or greater in 5.2% of normal pregnancies, in 92.6% of
      those with trisomy 21, in 88.5% of those with trisomy 18 or 13 and in 85.6% of
      those with other chromosomal defects. The detection rates for trisomy 21 were
      about 75% and 80% for respective false-positive rates of 1% and 2%. In the
      proposed individual risk-orientated two-stage screening for a risk cut-off of 1
      in 100 the total false-positive rate would vary with the method used for the
      second stage of screening from 2.1% for absence of the nasal bone to 2.7% for
      increased impedance in the ductus venosus and 2.7% for tricuspid regurgitation
      and the respective detection rates would be 92.0%, 94.2% and 91.7%. CONCLUSIONS:
      First-trimester combined screening for trisomy 21 is associated with a detection
      rate of about 90% for a false-positive rate of 5%. Individual risk-orientated two
      stage screening for trisomy 21 can potentially identify, in the first trimester
      of pregnancy, more than 90% of affected fetuses for a false-positive rate of 2
      3%.

PMID- 15736187
TI  - Role of n-methyl pyrrolidone in the enhancement of aqueous phase transdermal
      transport.
AB  - The role of n-methyl pyrrolidone (NMP) as an enhancer for permeants delivered
      from an aqueous phase was investigated in the transdermal delivery of the local
      anesthetics lidocaine free base, lidocaine-hydrochloride (HCl), and prilocaine
      HCl. Lidocaine free-base flux increased from H2O/NMP binary systems containing
      over 50% (v/v) NMP with significant flux enhancement observed above 80% NMP. In
      this range, drug flux was found to correlate with NMP flux. The addition of oleic
      acid (1% w/v) further enhanced lidocaine flux sixfold, in these formulations. The
      H2O/NMP (50% v/v) system enhanced the transport of water-soluble hydrochloride
      salt derivatives of lidocaine and prilocaine by factors of 4.3 and 2.6,
      respectively, indicating that NMP was capable of enhancing hydrophilic and
      hydrophobic drugs from an aqueous phase. These findings were consistent with the
      model that NMP flux across the stratum corneum improves the transport of
      formulation solutes.

PMID- 15736188
TI  - The fetal heart or the lymphatic system or ...? The quest for the etiology of
      increased nuchal translucency.

PMID- 15736189
TI  - Silicone oil induced aggregation of proteins.
AB  - Prior to delivery to the patient, protein pharmaceuticals often come in contact
      with a variety of surfaces (e.g., syringes and stoppers), which are treated to
      facilitate processing or to inhibit protein binding. One such coating, silicone
      oil, has previously been implicated in the induction of protein aggregation. We
      have investigated the propensity of model proteins to aggregate when silicone oil
      is present in solution and find significant induction of aggregation in four
      proteins of various molecular weights and isoelectric points in the presence of
      0.5% oil. The ability of silicone oil to induce conformational changes that might
      be responsible for this aggregation was also examined by a combination of
      circular dichroism (CD) and derivative UV spectroscopy. Neither method produces
      evidence of large conformational changes or alterations in thermal stability
      although in a limited number of cases some small changes suggest the possibility
      of minor structural alterations. The most probable explanation for silicone oil
      induced aggregation is that the oil has direct effects on intermolecular
      interactions responsible for protein association through interaction with protein
      surfaces or indirectly through effects on the solvent.

PMID- 15736190
TI  - Influence of asymmetric donor-receiver ion concentration upon transscleral
      iontophoretic transport.
AB  - Recent in vitro and in vivo studies have suggested transscleral iontophoresis as
      a means for non-invasive drug delivery to the eye. However, there remains a lack
      of information of the iontophoretic transport behavior of the sclera. The
      objective of the present study was to investigate the effects of permeant
      concentration upon transscleral iontophoretic transport. Constant current direct
      current (DC) iontophoresis was conducted with rabbit sclera in vitro at permeant
      concentration ranging from 0.015 to 1.0 M in the donor chamber without background
      electrolyte at 0.4-4 mA (current density: 2-20 mA/cm2). PBS (0.15 M) was the
      receiver solution. Salicylate (SA) and tetraethylammonium (TEA) were the model
      ionic permeants, and mannitol was the neutral probe permeant. Conductivity
      experiments of SA and TEA solutions were performed to determine the effects of
      ion concentration upon SA and TEA electromobilities. Model simulations were
      carried out and compared with the experimental data. It was found that the fluxes
      of the ionic permeants increased linearly with the electric current but were
      relatively independent of their donor concentrations. Electric field-induced
      convective solvent flow (electroosmosis) in the sclera was observed to be from
      the anode to cathode, suggesting that the sclera is net negatively charge at
      neutral pH. For the studied permeants, electrophoresis was the main transport
      enhancing mechanism with electroosmosis as a secondary effect. No significant
      interaction between the permeants and sclera was observed that significantly
      altered electroosmosis in the membrane. Under the asymmetric donor and receiver
      conditions, the transference of the permeants could not be predicted by the
      concentrations of the ions in the donor and receiver chambers with the assumption
      of constant electric field in the membrane. The membrane ion concentrations were
      different from those in the chambers due to the requirement of charge neutrality
      in the membrane.

PMID- 15736191
TI  - Enhanced buccal mucosal retention and reduced buccal permeability of estradiol in
      the presence of padimate O and Azone: a mechanistic study.
AB  - In previous experiments, it was suggested that the reduction in estradiol (E2)
      buccal permeability after pretreatment with some skin penetration enhancers was
      attributed to enhanced membrane storage. To verify this, further in vitro
      permeability experiments were performed and the kinetics of E2 buccal mucosal
      uptake and permeability was assessed. Porcine buccal mucosa was pretreated with
      the skin penetration enhancers octisalate, padimate O (PO), or Azone (AZ) and
      placed in modified Ussing chambers. The disappearance of E2 from the donor
      chamber and appearance of E2 in the receptor chamber was then monitored over 4 h.
      The final concentration of E2 associated with the buccal mucosa and donor chamber
      walls in the presence of each enhancer was also determined. The rate of E2
      disappearance from the donor chamber was 3.1-fold greater than the rate of E2
      appearance in the receptor chamber, indicating significant membrane storage of
      E2. Pretreatment with PO and AZ significantly increased the rate of E2
      disappearance and reduced the rate of E2 appearance in the receptor chamber. The
      corresponding enhancement in E2 tissue concentration after PO and AZ pretreatment
      was 1.7- and 3-fold, respectively. However, PO and AZ also increased the amount
      of E2 adsorbed to the walls of the donor chamber, which contributed to the
      reduction in E2 flux through the buccal mucosa.

PMID- 15736192
TI  - Microemulsions as colloidal vehicle systems for dermal drug delivery. Part V:
      Microemulsions without and with glycolipid as penetration enhancer.
AB  - The aim of this study was to investigate the dermal administration of a highly
      hydrophilic model drug, diphenhydramine (DPH), in colloidal systems with an
      aqueous colloidal phase in the presence of a glycolipid (GL) as a penetration
      modifier. Dermal penetration of DPH, GL, and isopropylpalmitate (IPP) from ME
      systems without GL and with GL as well as from a hydrogel used as standard
      formulation were estimated in vitro using human skin. The penetration of the
      drug, the oil (IPP), and the GL was measured with highly sensitive HPLC, HPLC-MS,
      and GC-MS assays, respectively. It could be shown that penetration modifier GL is
      penetrating very fast, and to a high extent into and through the human skin. In
      contrast, the penetration of IPP used as oily phase in the ME is limited. When
      incorporated in the ME systems GL and DPH was accumulated in the viable epidermis
      and in the dermis. Using ME containing a penetration modifier such as GL, a
      slight additional enhancing effect could be observed, particularly concerning the
      penetration of DPH into the acceptor fluid when a highly hydrophilic drug such as
      DPH was applied.

PMID- 15736193
TI  - Structural and analytical characterization of three hydrates and an anhydrate
      form of risedronate.
AB  - Four hydration states are reported for Risedronate monosodium. A single-crystal X
      ray structure determination is provided as proof of assignment for the
      monohydrate, hemi-pentahydrate, and variable hydrate forms. The structure
      provided for the anhydrate form was determined through simulating annealing
      calculations and subsequent Reitveld refinement of a high-quality X-ray powder
      diffraction patterns Favorable comparisons of experimentally obtained X-ray
      powder patterns are made to those generated from the single crystal data.
      Characteristic infrared, Raman, and NMR spectra are provided and discussed for
      each form as are thermal analysis profiles. In addition, photomicrographs are
      provided for each of the forms isolated for this study. The hemi-pentahydrate is
      demonstrated to be the equilibrium form at room temperature and 37 degrees C, in
      the presence of water.

PMID- 15736194
TI  - Interspecies scaling of biliary excreted drugs: a comparison of several methods.
AB  - The objective of this study was to evaluate the predictive performance of several
      methods of interspecies scaling for the prediction of human clearance of drugs
      which are excreted in the bile. Ten methods of allometric scaling were used to
      predict human clearance of biliary excreted drugs from animal data. The methods
      included the simple allometric approach; the rule of exponents; the rule of
      exponents with a correction factor; the ratio of human and monkey liver blood
      flow x monkey clearance; product of clearance and bile flow; product of clearance
      and UDGPT; product of clearance, bile flow, and UDGPT; and a modified version of
      the last three approaches in association with the rule of exponents. The results
      of the study indicate that among these ten approaches, the rule of exponents with
      the correction factor is the best approach for the prediction of human clearance
      for drugs which are excreted in the bile. The worst approach is the product of
      clearance, bile flow, and UDGPT. The simple allometry and the monkey liver blood
      flow (MLBF) approaches gave almost similar results. For some drugs the simple
      allometry predicted clearance better than the MLBF approach and vice versa.

PMID- 15736195
TI  - Using terahertz pulsed spectroscopy to quantify pharmaceutical polymorphism and
      crystallinity.
AB  - Terahertz pulsed spectroscopy (TPS) is a new technique that is capable of
      eliciting rich information when investigating pharmaceutical materials. In
      solids, it probes long-range crystalline lattice vibrations and low energy
      torsion and hydrogen bonding vibrations. These properties make TPS potentially an
      ideal tool to investigate crystallinity and polymorphism. In this study four
      drugs with different solid-state properties were analyzed using TPS and levels of
      polymorphism and crystallinity were quantified. Carbamazepine and enalapril
      maleate polymorphs, amorphous, and crystalline indomethacin, and thermotropic
      liquid crystalline and crystalline fenoprofen calcium mixtures were quantified
      using partial least-squares analysis. Root-mean-squared errors of cross
      validation as low as 0.349% and limits of detection as low as approximately 1%
      were obtained, demonstrating that TPS is an analytical technique of potential in
      quantifying solid-state properties of pharmaceutical compounds.

PMID- 15736196
TI  - Water adsorption kinetics and contact angles of pharmaceutical powders.
AB  - Water sorption kinetics and water contact angles have been characterized for a
      range of pharmaceutical powders: ambroxol hydrochloride, griseofulvin, N,n-octyl
      D-gluconamide, paracetamol, sulfathiazole, and theophylline. The uptake of water
      by powder samples at saturated vapor pressure was modeled using a pseudo first
      order kinetic relationship. Parameters from this model have been correlated with
      the concentration and reactivity of the active surface sites of the
      pharmaceutical powders and their contact angles. The study has shown that
      analysis of water adsorption kinetics can be a powerful technique for
      characterizing the surface chemistry and wettability of pharmaceutical powders,
      and is particularly sensitive to their surface modification through excipient
      adsorption: ethyl(hydroxyethyl)cellulose treatment of griseofulvin and butyryl
      chloride treatment of sulfathiazole are reported as case studies.

PMID- 15736197
TI  - Bioconversion of naltrexone and its 3-O-alkyl-ester prodrugs in a human skin
      equivalent.
AB  - The purpose of this study was to compare the percutaneous absorption and
      bioconversion of naltrexone (NTX), naltrexone-3-O-valerate (VAL), and naltrexone
      3-O-(2'-ethylbutyrate) (ETBUT) in a human skin equivalent model (EpiDerm) and in
      fresh human skin in vitro. NTX diffusion and metabolism to 6-beta-naltrexol
      (NTXol) were quantitated and compared in the EpiDerm and in excised fresh human
      skin. VAL and ETBUT diffusion and bioconversion studies were also completed in
      EpiDerm. Naltrexone bioconverted to levels of 3+/-2% NTXol in the EpiDerm and 1+/
      0.5% in fresh human skin. VAL hydrolyzed rapidly in the EpiDerm and mainly (93+/
      4%) NTX was found in the receiver compartment, similar to human skin. More intact
      ETBUT permeated the EpiDerm tissue compared to VAL, and only 15+/-11% NTX was
      found in the receiver. Significantly higher fluxes of NTX and the prodrugs were
      observed with the EpiDerm compared to human skin. A similar flux enhancement
      level was observed for VAL, compared to NTX base, in the EpiDerm and the human
      skin. Metabolically active human epidermal models like EpiDerm are useful as an
      alternative experimental system to human skin for prediction of
      topical/transdermal drug/prodrug bioconversion.

PMID- 15736198
TI  - Ultrasonographic signs of twin-twin transfusion syndrome in a monoamniotic twin
      pregnancy.

PMID- 15736199
TI  - Prenatal laser treatment of a placental chorioangioma.
AB  - Large placental chorioangiomas are rare complications in pregnancy. We present a
      case of a placental chorioangioma, complicated by polyhydramnios, in which
      obliteration of its blood supply using diode laser coagulation at 25 weeks of
      gestation was followed by an uneventful pregnancy and delivery of a healthy baby
      with a normal follow-up at the age of 9 months. Laser coagulation of the feeding
      vessels seems to be an effective treatment for chorioangiomas when the blood
      supply is superficial and the feeding vessels are small in diameter.

PMID- 15736201
TI  - Growth hormone expression in the perinatal and postnatal rat lung.
AB  - It is now established that the lung is a target site for pituitary growth hormone
      (GH) action, because pathophysiological states of pituitary GH excess and
      deficiency are associated with impaired pulmonary function. The onset of lung
      development and differentiation is, however, before the ontogenic differentiation
      of pituitary somatotrophs. GH may be involved, nevertheless, in lung development,
      because it is present in extrapituitary tissues of preimplantation mouse embryos
      and in the lung buds of embryonic chickens. The possibility that GH may be
      expressed in the rat lung during fetal and neonatal development, therefore, has
      been assessed. GH mRNA was detected in the lung, and its 693-bp sequence was
      identical to that in the pituitary gland. By in situ hybridization, this
      transcript was found to be abundantly expressed in the lungs of embryonic day
      (ED) 17 rats in mesenchymal, mucosal epithelial, and smooth muscle cells. This
      transcript was expressed in neonates until at least day 14 postnatally and was
      localized to type I and II epithelial cells and to pulmonary tissue macrophages
      and alveolar macrophages. GH immunoreactivity paralleled GH mRNA cellular
      localization throughout the time course studied. This immunoreactivity was
      specific and was lost after antibody preabsorption. The perinatal and postnatal
      lung is, therefore, an extrapituitary site of GH gene expression during
      development. Given that the GH receptor is present in the lung from early
      development, lung GH may have autocrine and/or paracrine roles in lung growth or
      differentiation or in pulmonary function.

PMID- 15736202
TI  - Dynamic morphological changes in the anterior vaginal wall before and after
      laparoscopic Burch colposuspension in primary urodynamic stress incontinence.
AB  - OBJECTIVE: To evaluate dynamic morphological changes in the anterior vaginal wall
      in primary urodynamic stress incontinence before and after laparoscopic Burch
      colposuspension and to explore the related effects on urethral and voiding
      functions. METHODS: Ultrasound cystourethrography and urodynamic study were
      performed in 112 patients with primary urodynamic stress incontinence before and
      3 months after laparoscopic Burch colposuspension. Ultrasound assessment included
      measurement of the bladder neck positions at rest and during straining, the
      bladder wall thickness at the dome and trigone, and observation of the motion of
      the bladder neck in addition to the development of cystocele on Valsalva
      maneuver. On ultrasonography, a cystocele was defined as prolapse or descent of
      the bladder base below the bladder neck at rest, on Valsalva, or both. RESULTS:
      After laparoscopic Burch colposuspension, ultrasound cystourethrography revealed
      significant differences in the bladder neck position at rest and during stress
      (preoperative median 93 degrees vs. postoperative 70 degrees at rest and
      preoperative 160 degrees vs. postoperative 81 degrees during stress, P < 0.001,
      respectively) and rotational angle (preoperative median 58 degrees vs.
      postoperative 10 degrees , P < 0.001). A laparoscopic Burch operation corrected
      50% (5/10) of the preoperative cystoceles. However, a residual cystocele
      developed postoperatively in 29% (30/102) of the women who did not have one
      previously. Postoperative ultrasonographic and urodynamic studies did not reveal
      any differences between those women with or without postoperative cystocele
      except for the residual urine volume, detrusor opening pressure, and straining
      and rotational angles of the bladder neck (P < 0.001, 0.032, 0.010 and < 0.001,
      respectively). CONCLUSIONS: Laparoscopic Burch colposuspension may correct a pre
      existing cystocele, but in other patients a cystocele may persist or be
      disclosed. After laparoscopic Burch operation a persistent cystocele is not
      associated with urethral compression or voiding impairment.

PMID- 15736203
TI  - Perinatal management of right aortic arch with aberrant left subclavian artery
      associated with critical stenosis of the subclavian artery in a newborn.
AB  - A right-sided aortic arch with an aberrant left subclavian artery is a congenital
      vascular anomaly that is easily detectable in utero at the level of the three
      vessels and trachea view, but which is rarely symptomatic in the neonate. We
      present a newborn with prenatally diagnosed right-sided aortic arch and aberrant
      subclavian artery who showed a clinically relevant stenosis of the subclavian
      artery during the first week of life. An intravascular stent was implanted into
      the stenosis of the aberrant left subclavian artery by catheterization. This case
      report demonstrates that a right-sided aortic arch with an aberrant subclavian
      artery can be diagnosed prenatally, that in these patients a stenosis of the
      subclavian artery can occur in early infancy and requires awareness of the
      neonatologist or pediatrician, and that stent implantation represents a minimally
      invasive therapeutic approach.

PMID- 15736204
TI  - Non-surgical management of live ectopic pregnancy with ultrasound-guided local
      injection: a case series.
AB  - OBJECTIVES: To describe a series of consecutive cases of live ectopic pregnancies
      managed with ultrasound-guided local injection of methotrexate (MTX) or potassium
      chloride (KCl). METHODS: Eighteen consecutive women with live and unruptured,
      tubal, cornual or cervical ectopic pregnancies referred to our unit for
      evaluation and management underwent risk-benefit counseling. Under transvaginal
      ultrasound guidance, puncture and injection of the ectopic pregnancy was
      performed using an automated puncture device. Either MTX or KCl was injected,
      producing immediate cessation of fetal cardiac activity. RESULTS: Of the 18
      ectopic pregnancies, 10 were cervical, four were tubal and four were cornual. The
      mean initial beta-hCG level was 33 412 IU and the mean gestational age was 6 + 6
      weeks. Ten ectopic gestational sacs were injected with KCl and eight were
      injected with MTX. There was no difference in time to resolution of the ectopic
      pregnancies between those injected with KCl and those with MTX. CONCLUSIONS:
      Unruptured live ectopic pregnancies of many types can be successfully managed
      without surgical intervention through local injection of KCl or MTX.

PMID- 15736205
TI  - The output display standard: has it missed its target?

PMID- 15736206
TI  - Ischiopagus conjoined twins at 9 weeks of gestation: three-dimensional ultrasound
      and power Doppler findings.

PMID- 15736207
TI  - Accuracy of magnetic resonance imaging for measuring fetal sheep lungs and other
      organs.
AB  - OBJECTIVE: Lung volume measurement by fetal magnetic resonance imaging (fetMRI)
      has been used to predict survival of fetuses with isolated congenital
      diaphragmatic hernia (CDH). So far, the accuracy and precision of fetMRI for
      volumetry of either the normal or hypoplastic developing lung has not been
      formally studied. METHODS: A total of nine sheep carrying 14 fetuses underwent
      fetMRI under general anesthesia at a mean of 118 days' gestational age (term =
      145 days). A total of 61 organs were measured in nine normal fetal sheep and five
      that underwent surgical creation of diaphragmatic hernia (DH), so as to induce
      pulmonary hypoplasia. Lungs were measured on T2-WI (weighted images) in three
      different planes, while liver and kidneys were measured in the axial (T1-WI) and
      sagittal (T2-WI) planes, respectively. Necropsy was done within 24 h after fetMRI
      to determine the volume postmortem by the water displacement method. Values were
      linearly correlated and a Bland and Altman analysis was done for volume
      measurement comparison, calculating means +/- SD, bias (mean of the difference of
      volume measurements), precision (SD of the difference) and absolute and
      proportionate limits of agreement for both methods. The accuracy of fetMRI volume
      measurement was determined for different organ groups by calculating the median
      relative error and precision index, both being measures of error in proportion to
      the magnitude of the volume measured, as a clinically relevant proxy of potential
      errors. RESULTS: The fetMRI volume measurements were on average larger than
      postmortem volumes, except for the kidneys. Kidney volume determination had a
      relative error of 29%, while measurements of larger organs had larger relative
      errors (42% for liver). Normal lungs were less accurately measured in the coronal
      or sagittal than in the axial plane (relative error 53%, 73% and 38%,
      respectively; P < 0.05 for sagittal vs. axial). Axially-measured lung volumes
      were more accurate for lungs of normal sheep compared to DH lungs (relative error
      38% vs. 73%, respectively; P < 0.05). CONCLUSION: FetMRI measured systematically
      higher volumes for organs such as fetal liver or lung. This may be related to
      fluid loss or lack of perfusion at the time of necropsy. Measurement of lung
      volume by fetMRI was most accurate in the axial plane. Measurements of lung and
      liver volumes by fetMRI in normal sheep were both in agreement with volumes
      measured at necropsy. Loss of accuracy for DH-lungs in comparison with the
      accuracy when measuring other similarly small organs, such as kidneys, suggests
      that fetMRI measurements can be less accurate for hypoplastic lungs related to
      CDH. With improving hardware, it might become easier to render the fetal lung and
      determine its volume reliably.

PMID- 15736210
TI  - Limitations of conservative treatment for repeat Cesarean scar pregnancy.

PMID- 15736211
TI  - Measurement of nuchal skin fold thickness in the second trimester: influence of
      imaging angle and fetal presentation.
AB  - OBJECTIVE: To assess the effect of imaging angle and fetal presentation on the
      measurement of nuchal skin fold thickness (NFT) in the second trimester. METHODS:
      Fetal NFT was prospectively measured in 921 women at 18-21 weeks' gestation. The
      population was divided into two groups according to fetal presentation. Group A
      comprised 643 fetuses in cephalic or transverse presentation and Group B
      comprised 278 fetuses in breech presentation. To determine whether there was a
      difference in NFT depending on imaging angle, in Group A the NFT was measured on
      the standard axial horizontal images and then on images obtained after moving the
      transducer about 30 degrees toward the occiput. In Group B an assessment was made
      as to whether NFT changed with fetal presentation. Initial measurements were made
      with the fetuses in breech presentation. Repeat NFT measurements were made after
      15 min in 64 fetuses that had converted to cephalic or transverse presentation.
      Statistical analysis was performed using a paired t-test. RESULTS: The mean NFT
      on the standard horizontal image was 5.2 mm, while that on the 30 degrees occiput
      image was 4.0 mm. The difference was significant (P < 0.001). One hundred and
      twenty-three (19.1%) fetuses had a NFT greater than 6 mm on the standard image,
      but only two (0.3%) had an NFT of > 6 mm on the 30 degrees occiput image. There
      were no chromosomal or structural abnormalities in the 123 fetuses in which the
      NFT was > 6 mm. The mean NFT of 64 fetuses in the breech presentation was 4.4 mm,
      while it was 3.9 mm when they had converted to other presentations. The
      difference was statistically significant (P = 0.001). In breech presentation,
      13/64 (20.3%) fetuses had a NFT greater than 6 mm compared to only one (1.6%)
      fetus in the other presentations. There were no structural or chromosomal
      abnormalities in any fetus with a NFT > 6 mm in either group. CONCLUSIONS: In
      this study the NFT measurement varied with scan direction and fetal presentation.
      To avoid falsely thickened NFT measurements the scan should be directed to image
      the posterior surface of the occipital bone. This can be achieved by scanning
      from a 30 degrees occipital direction. Also, NFT is greater in fetuses in a
      breech presentation. Attention to these details can reduce false-positive NFT
      measurements.

PMID- 15736212
TI  - Sonographic measurement of cervical length in threatened preterm labor in
      singleton pregnancies with intact membranes.
AB  - OBJECTIVES: To predict when delivery will occur, within 48 h and 7 days of
      presentation and before 35 weeks' gestation in women presenting with threatened
      preterm labor. METHODS: Sonographic measurement of cervical length was carried
      out in 510 women with singleton pregnancies presenting with threatened preterm
      labor and intact membranes at 24 to 33 + 6 weeks of gestation. The measurement
      was not taken into account in the subsequent management of the pregnancies. The
      outcome measures were delivery within 48 h and 7 days of presentation and
      delivery before 35 weeks. RESULTS: The median gestation at presentation was 30 +
      1 (range, 24 to 33 + 6) weeks and the median cervical length was 25 (range, 1-51)
      mm. Delivery within 48 h of presentation occurred in 21 (4.1%) cases, delivery
      within 7 days occurred in 43 (8.4%) and delivery before 35 weeks occurred in 76
      (14.9%). Logistic regression analysis demonstrated that the only significant
      independent predictor of delivery within 48 h was cervical length (odds ratio
      (OR), 0.73; 95% CI, 0.65-0.81) and for delivery within 7 days the independent
      predictors were cervical length (OR, 0.69; 95% CI, 0.63-0.76) and vaginal
      bleeding (OR, 19.42; 95% CI, 3.87-97.4). In the subgroup of women who did not
      deliver within 7 days of presentation, the incidence of delivery before 35 weeks
      was 7.1% (33 of 467) and the only significant independent predictor of such
      delivery was cervical length (OR, 0.92; 95% CI, 0.88-0.96, P < 0.0001). There was
      no significant independent contribution to any of the outcome measures from
      ethnic group, maternal age, gestational age, body mass index, parity, cigarette
      smoking or use of tocolytics. CONCLUSIONS: In women with threatened preterm labor
      sonographic measurement of cervical length helps to distinguish between true and
      false labor and to predict early preterm delivery.

PMID- 15736213
TI  - Coronary complications of percutaneous coronary intervention: a practical
      approach to the management of abrupt closure.

PMID- 15736214
TI  - Nipple-areola complex reconstruction using badge flap and intradermal tattooing.

PMID- 15736215
TI  - Colonic epithelial apoptosis during conventional and endoluminal aortic surgery.
AB  - BACKGROUND: This study characterized the initial modes of colonic mucosal injury
      during aneurysm surgery and correlated these with proinflammatory cytokine
      release into the colonic and systemic circulations. METHODS: Twenty-four patients
      undergoing conventional open aortic aneurysm repair and ten who had endovascular
      aneurysm repair (EVAR) were recruited. Mucosal biopsies were taken from the
      sigmoid colon immediately before and after surgery, for histological examination.
      Inferior mesenteric vein (IMV) and peripheral blood from patients who had
      conventional surgery was assayed for interleukin (IL) 1 beta, IL-6 and tumour
      necrosis factor (TNF) alpha. Only peripheral blood from patients who had EVAR was
      assayed. RESULTS: Conventional aneurysm repair resulted in a threefold increase
      in columnar epithelial apoptosis. There was a 26-fold increase in IL-6 in IMV
      blood within 5 min of reperfusion, with an equivalent rise in peripheral blood
      after 30 min. A 20-fold rise in peripheral blood TNF-alpha was observed after
      surgery. Splanchnic IL-6 correlated positively with cross-clamp time and
      increased apoptosis. No histological changes were seen after EVAR. There were no
      intraoperative cytokine changes during EVAR, although a postoperative increase in
      IL-6 and TNF-alpha was observed. CONCLUSION: The lack of columnar epithelial
      apoptosis following EVAR reflects the relatively minor ischaemic injury incurred
      during this procedure.

PMID- 15736216
TI  - Relationship between hormone receptor status and tumour size, grade and comedo
      necrosis in ductal carcinoma in situ.
AB  - BACKGROUND: Results of the National Surgical Adjuvant Breast Project B-24 trial
      indicate that adjuvant tamoxifen therapy is of benefit only in oestrogen receptor
      (ER)- positive ductal carcinoma in situ (DCIS). In the UK, ER status is not
      routinely determined in DCIS. The aim of this study was to assess the ER status
      in women with DCIS to determine whether any clinicopathological factors could
      predict positivity instead of immunohistochemical assessment. METHODS: The ER and
      progesterone receptor (PR) status of consecutive women diagnosed with DCIS during
      2001 and 2002 was determined by immunohistochemistry. RESULTS: One hundred and
      nineteen tumours diagnosed between 2001 and 2002 were analysed; 73.0 per cent
      were ER positive and 61.1 per cent were PR positive. PR positivity was associated
      with ER positivity (P < 0.001). Increasing tumour grade correlated with a
      decrease in ER and PR positivity (both P = 0.002). Comedo necrosis was associated
      with ER negativity (P = 0.026), PR negativity (P = 0.033) and a lower percentage
      of ER expression in ER-positive tumours (mean(s.d.) 82(27) versus 93(10) per
      cent; P = 0.021). CONCLUSION: Tumour grade and comedo necrosis were not strong
      enough predictors to be used as surrogates for immunohistochemical assessment. ER
      status should be determined before commencing endocrine therapy.

PMID- 15736217
TI  - Index for predicting mortality in elderly surgical patients.
AB  - BACKGROUND: The aim of the study was to validate a mortality index for use in
      patients over 65 years of age undergoing operative treatment or conservative
      management. METHODS: From a study conducted more than 20 years ago of elderly
      patients admitted with a surgical condition, 11 variables were identified as
      being significant in predicting mortality: age, white cell count, serum urea
      concentration, pulse rate, mean blood pressure, type of admission, urgency of
      operation, complexity of surgery, conservative management, and diagnostic
      categories of vascular disease and malignancy. Using multivariate logistic
      regression analysis, a mortality index was devised. This index was validated in a
      separate study of comparable patients treated in 1999-2001. RESULTS: Comparison
      of the derivation and validation data sets showed similarity in the distribution
      of variables with no significant difference in mortality (overall mortality rate
      9.3 per cent for the derivation set versus 9.6 per cent for the validation set;
      chi(2) = 0.084, 1 d.f., P = 0.771). Tests of calibration and discrimination
      showed no significant difference in predicted to actual deaths, and the receiver
      operator characteristic plots of the two data sets showed good discrimination.
      CONCLUSION: This mortality index was derived specifically for patients over 65
      years of age receiving either operative or conservative treatment. It could be of
      use when counselling patients and their relatives about the possible outcome of
      treatment.

PMID- 15736218
TI  - Non-invasive tests to predict fetal anemia in Kell-alloimmunized pregnancies.
AB  - OBJECTIVES: To compare test characteristics of ultrasound and Doppler parameters
      in the prediction of fetal anemia in Kell-alloimmunized pregnancies. METHODS: In
      this prospective study, 27 fetuses at risk for anemia due to Kell
      alloimmunization were evaluated with ultrasound and Doppler imaging. Spleen
      perimeter, liver length, middle cerebral artery (MCA) peak systolic velocity and
      intrahepatic umbilical venous (IHUV) maximum velocity were measured. Results were
      compared with fetal hemoglobin values at first intrauterine blood sampling or
      delivery. Severe fetal anemia was defined as a hemoglobin deficit of at least 5
      SD below the mean for gestational age. RESULTS: Eighteen fetuses were anemic and
      required intrauterine transfusions. In the other nine pregnancies no transfusions
      were performed; one of these fetuses was severely anemic at birth. MCA and IHUV
      flow velocities were the best predictors of fetal anemia in Kell alloimmunized
      fetuses (sensitivity 89% for each test). Sensitivities for spleen perimeter (15%)
      and liver length (14%) were disappointing. CONCLUSIONS: Doppler evaluation of MCA
      peak systolic velocity and IHUV maximum velocity can be used to reliably predict
      severe fetal anemia in Kell alloimmunization.

PMID- 15736219
TI  - Primary rectus abdominis myocutaneous flap for repair of perineal and vaginal
      defects after extended abdominoperineal resection.
AB  - BACKGROUND: Significant morbidity can result from perineal wounds, particularly
      after radiotherapy and extensive resection for cancer. Myocutaneous flaps have
      been used to improve healing. The purpose of this study was to evaluate the
      morbidity and results of primary rectus abdominis myocutaneous flap
      reconstruction of the vagina and perineum after extended abdominoperineal
      resection. METHODS: Thirty-one consecutive patients undergoing one-stage rectus
      abdominis myocutaneous flap reconstruction of extensive perineal wounds were
      studied prospectively. Twenty-six patients had surgery for recurrent or
      persistent epidermoid anal cancer or low rectal cancer, and 21 had high-dose
      preoperative radiotherapy. RESULTS: Three weeks after the operation, complete
      healing of the perineal wound was seen in 27 of the 31 patients. There were nine
      flap-related complications including three patients with partial flap necrosis,
      two with vaginal stenosis, one with vaginal scarring, one with small flap
      disunion and two with weakness of the anterior abdominal wall. There were no
      unhealed wounds at the completion of follow-up (median 9 months). CONCLUSION: The
      transpelvic rectus abdominis myocutaneous flap for the reconstruction of large
      perineal and vaginal wounds achieves wound healing with only moderate morbidity
      in the majority of patients after extensive abdominoperineal resection with or
      without radiotherapy.

PMID- 15736220
TI  - Isolated ectrodactyly caused by a heterozygous missense mutation in the
      transactivation domain of TP63.
AB  - We report a Mexican boy with isolated ectrodactyly (split hand malformation) in
      whom a new mutation was identified in exon 3 of the TP63 gene. In contrast to
      previously reported patients with isolated split hand/foot anomaly and mutations
      in the DNA binding domain of Tp63, the mutation described herein induce an amino
      acid substitution (R97C) in the canonical transactivation (TA) domain. To our
      knowledge, this is the first naturally occurring mutation described so far in
      this part of the protein. Based on the genotype-phenotype correlation observed in
      our patient, we hypothesize that integrity of the TA domain of Tp63 is critical
      for normal limb development.

PMID- 15736221
TI  - Carpal and tarsal synostoses and transverse reduction defects of the toes in two
      brothers heterozygous for a double de novo NOGGIN mutation.
AB  - We describe two siblings with carpal and tarsal synostoses associated with
      transverse deficiencies of the toes. Mutation analysis of the NOG gene revealed a
      double missense mutation in both boys resulting in Pro42Ala and Pro50Arg. The
      parents were clinically unaffected, and these two mutations were not detected in
      their white blood cells or buccal mucosa. This indicates the presence of gonadal
      mosaicism or a low level of somatic mosaicism in one of the parents.

PMID- 15736222
TI  - Cloning of cDNAs and the differential expression of A-type cyclins and Dmc1
      during spermatogenesis in the Japanese eel, a teleost fish.
AB  - We cloned A-type cyclins (cyclins A1 and A2) and Dmc1 cDNAs from the eel testis.
      Cyclin A1 mRNA was predominantly expressed in the livers, ovaries, and testes of
      the eels. In contrast to cyclin A1 mRNA, a very high expression of cyclin A2 mRNA
      was observed in the brains, livers, kidneys, spleens, ovaries, and testes of the
      eels. Dmc1 mRNA was predominantly expressed in the testes and ovaries; expression
      in the brain was also detected. In the eel testis, a few type-A spermatogonia
      incorporating 5-bromo-2'-deoxyuridine (BrdU) were seen before the initiation of
      spermatogenesis by hormonal induction. On day 1 after hormonal induction, the
      number of BrdU-labeled spermatogonia increased remarkably, and after 3 and 6
      days, many labeled type-B spermatogonia were also observed. The expression of
      cyclin A2 increased 1 day after the induction of spermatogenesis and reached a
      plateau after 6 days, when many type-B spermatogonia with high proliferative
      activity were found. In contrast, the expression of cyclin A1 mRNA was detected
      after 9 days, coincident with the first appearance of spermatocytes. Cyclin A1
      mRNA was localized in germ cells of all stages, from primary spermatocytes to
      round spermatids, whereas cyclin A2 mRNA was specifically localized in
      spermatogonia, secondary spermatocytes, round spermatids, and testicular somatic
      cells, including Sertoli cells. Dmc1 was localized only in the earlier stages of
      primary spermatocytes; before this stage, cyclin A1 mRNA was not detectable.
      Overall, cyclin A2, Dmc1, and cyclin A1 are expressed in spermatogenic cells
      sequentially before and during meiosis in the eel testis.

PMID- 15736223
TI  - Two nodal-responsive enhancers control left-right asymmetric expression of Nodal.
AB  - Asymmetric expression of Nodal in the lateral plate mesoderm (LPM) plays the
      major role in left-right (L-R) patterning. A Nodal-responsive enhancer located in
      the intron 1 (ASE) regulates asymmetric Nodal expression, but it is unknown how
      Nodal expression is initiated in the left LPM. Here, we have identified a second
      asymmetric enhancer (left side-specific enhancer, LSE) in the upstream region of
      mouse Nodal gene. LSE is also located in the corresponding region of human NODAL.
      L-R specificity of LSE is affected by iv and inv mutations. The requirement of a
      conserved FoxH1-binding sequence for LSE activity and the dependence of LSE
      activity on Nodal coreceptor Cryptic indicate that LSE is activated by Nodal
      signal. However, the mutant mouse lacking LSE does not show obvious L-R
      patterning defects. These results suggest that Nodal expression in the left LPM
      is induced by a combination of two Nodal-responsive autoregulatory enhancers, ASE
      and LSE.

PMID- 15736224
TI  - Neural control mechanisms of the pheromone-triggered programmed behavior in male
      silkmoths revealed by double-labeling of descending interneurons and a motor
      neuron.
AB  - Male silkmoths, Bombyx mori, exhibit a characteristic zigzagging behavior
      consisting of straight-line walking, zigzagging turns, and looping. The timing
      for shifting the turning direction is synchronized to the sideways head movements
      controlled by neck motor neurons (NMNs) including a cervical ventral NMN (cv1
      NMN). It has been suggested that this programmed behavior is instructed by two
      types of activity patterns descending from the brain and the thoracic ganglion:
      one is a phasic excitation and the other is a state-dependent activity similar to
      the flipflop in electric memory circuits. These activities are shown by certain
      descending interneurons contained in two subsets of DNs, Group-I and -II DNs.
      However, it is not yet well understood which DNs are directly related to
      instructing this behavior. In order to understand neural control mechanisms of
      this programmed behavior, we investigated the morphological relationship between
      these DNs and the cv1-NMN, which is an index of this programmed behavior. We
      applied a double-labeling technique combining backfilling of the cv1-NMN and
      intracellular staining of single DNs. 3D confocal images revealed overlapping
      regions between the Group-I, -II DNs and the cv1-NMN. Group-IIA and -IID, which
      showed typical flipflop activities, Group-IIC DNs, which showed phasic
      excitation, and Group-IB DNs, which showed long-lasting inhibition had many
      overlapping regions on the cv1-NMNs. Our results indicate that the programmed
      behavior is instructed by these types of DNs.

PMID- 15736225
TI  - Retinoid signaling competence and RARbeta-mediated gene regulation in the
      developing mammalian telencephalon.
AB  - To study retinoid signaling in the developing telencephalon, we transfected a
      retinoid reporter gene into different regions of developing telencephalon. We
      found that the ventral telencephalon was more competent to retinoid signaling
      than the dorsal telencephalon. Moreover, among all retinoic acid receptors (RARs)
      and retinoid X receptors (RXRs), RARbeta was strongly induced by retinoic acid in
      the ventral telencephalon, suggesting that RARbeta might be involved in retinoid
      signaling competence. The RT-PCR analysis indicated that RARbeta was selectively
      expressed in the developing striatum of ventral telencephalon. We then
      demonstrated that null mutations of RARbeta gene resulted in reduction of
      striatal-enriched tyrosine phosphatase (STEP) mRNA in the striatum of RARbeta-/-
      mutant mice. Conversely, the gain-of-function study showed that ectopic
      expression of RARbeta1 in the cerebral cortex enhanced STEP expression, and the
      effect was RARbeta-isoform specific. Our study identified RARbeta as an important
      molecule for transducing retinoid signals in developing ventral telencephalon.

PMID- 15736226
TI  - Central inhibitory microcircuits controlling spike propagation into sensory
      terminals.
AB  - The phenomenon of afferent presynaptic inhibition has been intensively studied in
      the sensory neurons of the chordotonal organ from the coxobasal joint (CBCO) of
      the crayfish leg. This has revealed that it has a number of discrete roles in
      these afferents, mediated by distinct populations of interneurons. Here we
      examine further the effect of presynaptic inhibition on action potentials in the
      CBCO afferents and investigate the nature of the synapses that mediate it. In the
      presence of picrotoxin, the action potential amplitude is increased and its half
      width decreased, and a late depolarizing potential following the spike is
      increased in amplitude. Ultrastructural examination of the afferent terminals
      reveals that synaptic contacts on terminal branches are particularly abundant in
      the neuropil close to the main axon. Many of the presynaptic terminals contain
      small agranular vesicles, are of large diameter, and are immunoreactive for gamma
      aminobutyric acid (GABA). These terminals are sometimes seen to make reciprocal
      connections with the afferents. Synaptic contacts from processes immunoreactive
      for glutamate are found on small-diameter afferent terminals. A few of the
      presynaptic processes contain numerous large granular vesicles and are
      immunoreactive for neither GABA nor glutamate. The effect that the observed
      reciprocal synapses might have was investigated by using a multicompartmental
      model of the afferent terminal.

PMID- 15736227
TI  - Light and electron microscopic analysis of KChIP and Kv4 localization in rat
      cerebellar granule cells.
AB  - Potassium channels are key determinants of neuronal excitability. We recently
      identified KChIPs as a family of calcium binding proteins that coassociate and
      colocalize with Kv4 family potassium channels in mammalian brain (An et al.
      [2000] Nature 403:553). Here, we used light microscopic immunohistochemistry and
      multilabel immunofluorescence labeling, together with transmission electron
      microscopic immunohistochemistry, to examine the subcellular distribution of
      KChIPs and Kv4 channels in adult rat cerebellum. Light microscopic
      immunohistochemistry was performed on 40-microm free-floating sections using a
      diaminobenzidine labeling procedure. Multilabel immunofluorescence staining was
      performed on free-floating sections and on 1-microm ultrathin cryosections.
      Electron microscopic immunohistochemistry was performed using an immunoperoxidase
      pre-embedding labeling procedure. By light microscopy, immunoperoxidase labeling
      showed that Kv4.2, Kv4.3, and KChIPs 1, 3, and 4 (but not KChIP2) were expressed
      at high levels in cerebellar granule cells (GCs). Kv4.2 and KChIP1 were highly
      expressed in GCs in rostral cerebellum, whereas Kv4.3 was more highly expressed
      in GCs in caudal cerebellum. Immunofluorescence labeling revealed that KChIP1 and
      Kv4.2 are concentrated in somata of cerebellar granule cells and in synaptic
      glomeruli that surround synaptophysin-positive mossy fiber axon terminals.
      Electron microscopic analysis revealed that KChIP1 and Kv4.2 immunoreactivity is
      concentrated along the plasma membrane of cerebellar granule cell somata and
      dendrites. In synaptic glomeruli, KChIP1 and Kv4.2 immunoreactivity is
      concentrated along the granule cell dendritic membrane, but is not concentrated
      at postsynaptic densities. Taken together, these data suggest that A-type
      potassium channels containing Kv4.2 and KChIP1, and perhaps also KChIP3 and 4,
      play a critical role in regulating postsynaptic excitability at the cerebellar
      mossy-fiber/granule cell synapse.

PMID- 15736228
TI  - Retinotectal transmission in the optic tectum of rainbow trout.
AB  - Retinotectal transmission has not yet been well characterized at the cellular
      level in the optic tectum. To address this issue, we used a teleost, the rainbow
      trout, and characterized periventricular neurons as postsynaptic cells expected
      to receive the retinotectal inputs to the optic tectum. The somata of
      periventricular neurons are localized in the upper zone of the stratum
      periventriculare (SPV), whereas the lower zone of the SPV comprises the cell body
      layer of radial glial cells. Ca2+ imaging identified functional ionotropic
      glutamate receptors in periventricular neurons. We also cloned cDNAs encoding the
      NR1 subunit of N-methyl-D-aspartic acid (NMDA) receptors and the GluR2 subunit of
      (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors,
      and detected their mRNAs in periventricular neurons by in situ hybridization. The
      presence of the receptor subunit proteins was also confirmed in the dendrites of
      periventricular neurons by immunoblotting and immunohistochemistry. On the other
      hand, radial glial cells in the lower zone of the SPV did not respond to
      glutamate applications, and mRNA and immunoreactivities of ionotropic glutamate
      receptors were not detected in glial cells. The present findings suggest that
      glutamatergic transmission at synapses between retinotectal afferents and
      periventricular neurons is mediated by the functional NMDA and AMPA receptors.

PMID- 15736229
TI  - Localization of nitric oxide synthase in the central complex and surrounding
      midbrain neuropils of the locust Schistocerca gregaria.
AB  - Nitric oxide (NO), generated enzymatically by NO synthase (NOS), acts as an
      important signaling molecule in the nervous systems of vertebrates and
      invertebrates. In insects, NO has been implicated in development and in various
      aspects of sensory processing. To understand better the contribution of NO
      signaling to higher level brain functions, we analyzed the distribution of NOS in
      the midbrain of a model insect species, the locust Schistocerca gregaria, by
      using NADPH diaphorase (NADPHd) histochemistry after methanol/formalin fixation;
      results were validated by NOS immunohistochemistry. NADPHd yielded much higher
      sensitivity and resolution, but otherwise the two techniques resulted in
      corresponding labeling patterns throughout the brain, except for intense
      immunostaining but only weak NADPHd staining in median neurosecretory cells.
      About 470 neuronal cell bodies in the locust midbrain were NADPHd-positive
      positive, and nearly all major neuropil centers contained dense, sharply stained
      arborizations. We report several novel types of NOS-expressing neurons, including
      small ocellar interneurons and antennal sensory neurons that bypass the antennal
      lobe. Highly prominent labeling occurred in the central complex, a brain area
      involved in sky-compass orientation, and was analyzed in detail. Innervation by
      NOS-expressing fibers was most notable in the central body upper and lower
      divisions, the lateral accessory lobes, and the noduli. About 170 NADPHd-positive
      neurons contributed to this innervation, including five classes of tangential
      neuron, two systems of pontine neuron, and a system of columnar neurons. The
      results provide new insights into the neurochemical architecture of the central
      complex and suggest a prominent role for NO signaling in this brain area.

PMID- 15736230
TI  - Projections from the spinal trigeminal nucleus to the cochlear nucleus in the
      rat.
AB  - The integration of information across sensory modalities enables sound to be
      processed in the context of position, movement, and object identity. Inputs to
      the granule cell domain (GCD) of the cochlear nucleus have been shown to arise
      from somatosensory brain stem structures, but the nature of the projection from
      the spinal trigeminal nucleus is unknown. In the present study, we labeled spinal
      trigeminal neurons projecting to the cochlear nucleus using the retrograde
      tracer, Fast Blue, and mapped their distribution. In a second set of experiments,
      we injected the anterograde tracer biotinylated dextran amine into the spinal
      trigeminal nucleus and studied the resulting anterograde projections with light
      and electron microscopy. Spinal trigeminal neurons were distributed primarily in
      pars caudalis and interpolaris and provided inputs to the cochlear nucleus. Their
      axons gave rise to small (1-3 microm in diameter) en passant swellings and
      terminal boutons in the GCD and deep layers of the dorsal cochlear nucleus. Less
      frequently, larger (3-15 microm in diameter) lobulated endings known as mossy
      fibers were distributed within the GCD. Ventrally placed injections had an
      additional projection into the anteroventral cochlear nucleus, whereas dorsally
      placed injections had an additional projection into the posteroventral cochlear
      nucleus. All endings were filled with round synaptic vesicles and formed
      asymmetric specializations with postsynaptic targets, implying that they are
      excitatory in nature. The postsynaptic targets of these terminals included
      dendrites of granule cells. These projections provide a structural substrate for
      somatosensory information to influence auditory processing at the earliest level
      of the central auditory pathways.

PMID- 15736231
TI  - RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory
      ganglia, and corticospinal tract neurons and long-lasting specific changes
      following spinal cord injury.
AB  - Inhibition of RhoA has been shown to enhance axonal regeneration following spinal
      cord injury. Here we mapped mRNA expression patterns of RhoA, B, and C, Rac1,
      Cdc42, and Tc10 in spinal cord, sensory ganglia, and sensorimotor cortex in
      uninjured rats, and following spinal cord injury or sham laminectomy. In the
      intact spinal cord, neurons displayed high levels of Rac1, Cdc42, and Tc10 mRNA
      hybridization signal. GFAP-immunoreactive astrocytes expressed primarily RhoB and
      Rac1, while oligodendrocyte-like cells expressed RhoA, Rac1, and Cdc42. Injury
      caused profound, long-lasting upregulation of RhoA, Rac1, Cdc42, and Tc10 mRNA in
      the spinal cord, while RhoB was modestly increased and RhoC did not change. GFAP
      immunoreactive reactive astrocytes exhibited a dramatic increase of RhoA mRNA
      expression along with increases of Rac1 and Cdc42. Injury also led to elevation
      of RhoA, Cdc42, and Tc10 in neurons and modest increases of RhoA, Rac1, and Tc10
      in oligodendrocyte-like cells. Laminectomy caused similar, but less pronounced
      alterations of investigated mRNA species. In dorsal root ganglia neuronal RhoA,
      Rac1, Cdc42, and Tc10 mRNA levels were increased similarly by spinal cord injury
      and sham surgery. The CST pyramidal cells expressed Tc10 mRNA and the CST itself
      was Tc10-immunoreactive. Tc10-immunoreactivity disappeared distal to injury. We
      conclude that there are gene-specific patterns of expression of the six different
      Rho-GTPases in normal spinal cord and dorsal root ganglia, and that specific
      changes of temporal and spatial expression patterns occur in response to spinal
      cord injury, suggesting different roles of these GTPases in the cellular sequelae
      of CNS injury.

PMID- 15736232
TI  - Axonal development in the cerebral white matter of the human fetus and infant.
AB  - After completion of neuronal migration to form the cerebral cortex, axons undergo
      rapid elongation to their intra- and subcortical targets, from midgestation
      through infancy. We define axonal development in the human parietal white matter
      in this critical period. Immunocytochemistry and Western blot analysis were
      performed on 46 normative cases from 20-183 postconceptional (PC) weeks. Anti-SMI
      312, a pan-marker of neurofilaments, stained axons as early as 23 weeks. Anti-SMI
      32, a marker for nonphosphorylated neurofilament high molecular weight (NFH),
      primarily stained neuronal cell bodies (cortical, subcortical, and Cajal
      Retzius). Anti-SMI 31, which stains phosphorylated NFH, was used as a marker of
      axonal maturity, and showed relatively low levels of staining (approximately one
      fourth of adult levels) from 24-34 PC weeks. GAP-43, a marker of axonal growth
      and elongation, showed high levels of expression in the white matter from 21-64
      PC weeks and lower, adult-like levels beyond 17 postnatal months. The onset of
      myelination, as seen by myelin basic protein expression, was approximately 54
      weeks, with progression to "adult-like" staining by 72-92 PC weeks. This study
      provides major insight into axonal maturation during a critical period of growth,
      over an age range not previously examined and one coinciding with the peak period
      of periventricular leukomalacia (PVL), the major disorder underlying cerebral
      palsy in premature infants. These data suggest that immature axons are
      susceptible to damage in PVL and that the timing of axonal maturation must be
      considered toward establishing its pathology relative to the
      oligodendrocyte/myelin/axonal unit.

PMID- 15736234
TI  - Carbonization of disclike molecules in porous alumina membranes: toward carbon
      nanotubes with controlled graphene-layer orientation.

PMID- 15736233
TI  - Synaptogenesis on mature hippocampal dendrites occurs via filopodia and immature
      spines during blocked synaptic transmission.
AB  - During development, dendritic spines emerge as stubby protrusions from single
      synapses on dendritic shafts or from retracting filopodia, many of which have
      more than one synapse. These structures are rarely encountered in the mature
      brain. Recently, confocal and two-photon microscopy have revealed a proliferation
      of new filopodia-like protrusions in mature hippocampal slices, especially when
      synaptic transmission was blocked. It was not known whether these protrusions
      have synapses nor whether they are accompanied by the other immature spine forms.
      Here, reconstruction from serial section electron microscopy (ssEM) was used to
      answer these questions. Acute hippocampal slices from mature male rats, ages 56
      and 63 days, were maintained in vitro in control medium or in a nominally calcium
      free medium with high magnesium, glutamate receptor antagonists, and sodium and
      calcium channel blockers. At the end of each 8-hour experiment, all slices were
      fixed, coded, and processed for ssEM. In agreement with light microscopy, there
      were more filopodia along dendrites in slices with blocked synaptic transmission.
      These filopodia were identified by their pointy tips and either the absence of
      synapses or presence of multiple synapses along them. There was also a
      proliferation of stubby spines. Filopodia along mature dendrites were typically
      shorter than developmental filopodia, with outgrowth likely being constrained by
      reduced extracellular space and compact neuropil, providing numerous candidate
      presynaptic partners in the vicinity of the mature dendrites. These findings
      suggest that synaptogenesis and spine formation are readily initiated under
      conditions of reduced activity in the mature brain.

PMID- 15736235
TI  - Developmental regulation of neuron-specific P2X3 receptor expression in the rat
      cochlea.
AB  - ATP-gated ion channels assembled from P2X3 receptor (P2X3R) subunits contribute
      to neurotransmission and neurotrophic signaling, associated with neurite
      development and synaptogenesis, particularly in peripheral sensory neurons. Here,
      P2X3R expression was characterized in the rat cochlea from embryonic day 16 (E16)
      to adult (P49-56), using RT-PCR and immunohistochemistry. P2X3R mRNA was strongly
      expressed in the cochlea prior to birth, declined to a minimal level at P14, and
      was absent in adult tissue. P2X3R protein expression was confined to spiral
      ganglion neurons (SGN) within Rosenthal's canal of the cochlea. At E16,
      immunolabeling was detected in the SGN neurites, but not the distal neurite
      projection within the developing sensory epithelium (greater epithelial ridge).
      From E18, the immunolabeling was observed in the peripheral neurites innervating
      the inner hair cells but was reduced by P6. However, from P2-8, immunolabeling of
      the SGN neurites extended to include the outer spiral bundle fiber tract beneath
      the outer hair cells. This labeling of type II SGN afferent fiber declined after
      P8. By P14, all synaptic terminal immunolabeling in the organ of Corti was
      absent, and SGN cell body labeling was minimal. In adult cochlear tissue, P2X3R
      immunolabeling was not detected. Noise exposure did not induce P2X3R expression
      in the adult cochlea. These data indicate that ATP-gated ion channels
      incorporating P2X3R subunit expression are specifically targeted to the afferent
      terminals just prior to the onset of hearing, and likely contribute to the
      neurotrophic signaling which establishes functional auditory neurotransmission.

PMID- 15736236
TI  - Negatively thermoresponsive membranes with functional gates driven by zipper-type
      hydrogen-bonding interactions.

PMID- 15736238
TI  - High-aspect-ratio TiO2 nanotubes by anodization of titanium.

PMID- 15736237
TI  - 1D arrangement of Au nanoparticles by the helical structure of schizophyllan: a
      unique encounter of a natural product with inorganic compounds.

PMID- 15736239
TI  - Orthogonally protected sugar diamino acids as building blocks for linear and
      branched oligosaccharide mimetics.

PMID- 15736240
TI  - Beyond the limit on percutaneous intervention of saphenous vein graft.

PMID- 15736241
TI  - In situ observation of a reversible single-crystal-to-single-crystal apical
      ligand-exchange reaction in a hydrogen-bonded 2D coordination network.

PMID- 15736242
TI  - Feasibility, safety, and preliminary efficacy of a novel ePTFE-covered self
      expanding stent in saphenous vein graft lesions: the Symbiot II trial.
AB  - Compared with percutaneous interventions in native coronary arteries,
      revascularization of saphenous vein graft (SVG) lesions is associated with
      increased rates of immediate and long-term major adverse cardiac events (MACE).
      The Symbiot II trial was a multicenter prospective study designed to evaluate the
      feasibility and safety of a novel self-expanding polytetrafluoroethylene (ePTFE)
      covered stent in the treatment of de novo and restenotic SVG lesions. The primary
      endpoint was MACE through 30 days postprocedure. Successful Symbiot stent
      deployment was achieved in 75 of 77 patients (97.4%) with SVG lesions < or = 35
      mm in length (visual assessment). The procedural success rate (defined as < 30%
      residual stenosis at the target site and no clinical complications) was 83%, and
      all study device procedures provided grade 3 TIMI flow postprocedure. Within the
      first 30 days postprocedure, four patients (5.2%) experienced MACE (defined as
      death, Q-wave or non-Q-wave myocardial infarction, and clinically driven target
      vessel revascularization), of whom three patients (3.9%) experienced
      periprocedural non-Q-wave myocardial infarction. No subacute stent thrombosis was
      observed over the 6-month follow-up period. No relevant luminal loss at the
      target site (mean, 0.3 +/- 0.9 mm) was observed in the 58 patients (77.3% of
      enrolled patients) who underwent quantitative coronary angiography at 6 months.
      The incidences of binary in-stent restenosis, in-segment restenosis, and target
      vessel failure (defined as acute and late-term MACE through 6 months
      postprocedure) were low (7.0%, 8.6%, and 14.3%, respectively). The Symbiot self
      expanding ePTFE membrane-covered stent was associated with a high procedural
      success rate (97.4%), low incidences of MACE at 30 days (5.2%) and 6 months
      (14.3%), suggesting that it is safe and effective in the treatment of SVG
      disease.

PMID- 15736243
TI  - Bleeding complications with PCI.

PMID- 15736244
TI  - Superiority of endovascular grafts compared to bare metal stents with transstent
      coil embolization for endovascular abdominal aortic aneurysm repair in patients
      at high risk for surgery.
AB  - We sought to determine the effectiveness of uncovered stents with aneurysm
      transstent coil embolization compared with endografts for percutaneous abdominal
      aortic aneurysm (AAA) repair. Thirty-six patients with AAA considered inoperable
      underwent endovascular repair using the Ancure bifurcated endograft or
      overlapping uncovered stents with transstent coil embolization. Procedural
      success, outcomes, serial aneurysm size, aneurysm blood flow, and growth ratios
      were compared between groups. One patient in each group died due to the procedure
      and two patients in the endograft cohort required acute surgical repair. After
      2.0 +/- 0.8 years of follow-up, three patients required endograft placement, four
      surgical repair, three had AAA rupture, with two AAA-related deaths in the
      uncovered stent group. No late deaths or surgical conversion occurred in the
      endograft group. The primary AAA flow exclusion and aneurysm expansion rate and
      growth were superior in the endograft group and during follow-up. In high-risk
      patients with AAA, the use of endografts was superior compared to uncovered
      stents with transstent coil embolization for endovascular repair.

PMID- 15736245
TI  - Retrograde percutaneous aortic valve implantation for critical aortic stenosis.
AB  - Recently, a prosthetic aortic valve has been implanted percutaneously in several
      patients using an antegrade transseptal approach. This has been shown to be
      feasible and associated with dramatic hemodynamic improvement. We report a
      retrograde implantation of a percutaneous heart valve (PHV) in an 84-year-old man
      with critical aortic stenosis and refractory congestive heart failure after
      difficulties encountered with an initial antegrade approach. While attempting
      antegrade transseptal implantation of a PHV, the anterior leaflet of the mitral
      valve was tethered by the guidewire resulting in severe mitral regurgitation and
      pulseless electrical activity. Cardiac resuscitation was successful. Utilizing a
      retrograde approach, the PHV was successfully implanted in a stable position
      below the coronary ostia and well above the mitral valve leaflets. The aortic
      valve area increased from 0.55 to 1.7 cm2 with only mild paravalvular aortic
      regurgitation. Despite marked improvement in aortic valve function, the patient
      died secondary to guidewire-induced mitral valve anterior leaflet laceration,
      severe mitral regurgitation, and cardiogenic shock. Retrograde implantation of a
      PHV can be successfully performed with substantial increase in aortic valve area
      and an acceptable degree of aortic regurgitation. Although the retrograde
      approach may be associated with greater risk of vascular access site
      complications, it may be considerably safer by avoiding potential guidewire
      injury to the mitral valve. Further refinements in technique may establish the
      retrograde approach as the preferred means of PHV implantation in nonsurgical
      patients with critical aortic stenosis.

PMID- 15736246
TI  - Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas
      microbubble carrier reduced neointimal formation in a porcine coronary restenosis
      model.
AB  - Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC)
      adheres to injured arteries and enhances the drug uptake specifically into the
      cells of the denuded vessel segment. The purpose of this study was to investigate
      the effect of PGMC-based systemic delivery of Rapamycin on expression of p27 in
      vascular tissue and restenosis in porcine coronary arteries after stent
      implantation. Eight pigs underwent coronary stent implantation (three stents per
      animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of
      Rapamycin and three animals served as control. Four hours postprocedure, three
      pigs were sacrificed and stented segments were analyzed by high-performance
      liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs
      (15 stent sites) were sacrificed at 28 days following intervention and vessels
      were perfusion-fixed. HPLC of the treated arteries demonstrated high drug
      concentration in the vessel tissue, and Western blot analysis showed elevated
      expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly
      reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with
      controls (1.84 +/- 0.84 vs. 4.77 +/- 1.71 mm2, respectively; P < 0.001). In the
      porcine coronary model, site-specific systemic delivery of Rapamycin utilizing
      PGMC resulted in overexpression of p27 and a significant reduction of neointimal
      formation within the stented segments.

PMID- 15736247
TI  - Invasive human magnetic resonance imaging: feasibility during revascularization
      in a combined XMR suite.
AB  - We tested the feasibility and safety of invasive magnetic resonance imaging (MRI)
      during peripheral angioplasty. Real-time MRI can image soft tissue and may
      potentially guide therapeutic procedures without ionizing radiation or
      nephrotoxic contrast. MRI-guided diagnostic catheterization has been described
      recently, but safe and conspicuous catheter devices are not widely available. An
      active guidewire, which serves as an MRI receiver antenna, might be useful to
      guide catheterization or even to image atheroma. We describe a combined
      interventional suite offering both X-ray fluoroscopy and real-time MRI. We used a
      0.030'' active guidewire receiver coil for invasive MRI after X-ray lesion
      traversal in patients undergoing percutaneous iliofemoral artery
      revascularization. Intravascular MRI was compared with noninvasive MRI, X-ray
      angiography, and intravascular ultrasound (IVUS). Seven eligible patients
      consented to participate, but three were excluded because of lengthy
      revascularization procedures. Four remaining patients safely underwent combined X
      ray fluoroscopy and real-time magnetic resonance imaging (XMR) transport,
      continuous monitoring, and all imaging modalities. There was no device
      dislodgment, contamination or evidence of heating. The intravascular MRI coil was
      well visualized except at the tip, but did not provide superior mural imaging
      compared with IVUS. Therefore, because an adequate safety and workflow experience
      was obtained, enrollment was terminated after only four subjects. Invasive MRI is
      feasible and apparently safe during peripheral angioplasty. Patients can safely
      be transported and monitored in an XMR interventional suite. An active quarter
      wavelength guidewire coil does not provide superior imaging compared with IVUS,
      but provides satisfactory guidewire visualization. These tools may prove useful
      for advanced therapeutic procedures in the future.

PMID- 15736249
TI  - Proximal protection during saphenous vein graft angioplasty: the Kerberos embolic
      protection system.
AB  - Percutaneous intervention in the setting of aortocoronary saphenous vein graft
      disease is associated with a significant risk of distal embolization. Devices
      intended to minimize the clinical impact of embolization have primarily utilized
      distally placed occlusive balloons or filters. Although such systems are often
      effective, distal protection does have limitations. We report a novel proximal
      embolic protection and rinsing system intended to overcome some of these
      limitations.

PMID- 15736248
TI  - Starc II, a multicenter randomized placebo-controlled double-blind clinical trial
      of trapidil for 1-year clinical events and angiographic restenosis reduction
      after coronary angioplasty and stenting.
AB  - The objective of this study was to investigate the effect of trapidil 200 mg
      t.i.d. in preventing the occurrence of death, of myocardial infarction and the
      need for repeat revascularization at 12 months after balloon PTCA with or without
      stenting. Coronary restenosis after stenting is still a major drawback of
      percutaneous coronary interventions (PCI) for 30-40% of patients. Trapidil has
      been shown to prevent restenosis after PTCA. Eligible patients were randomized to
      placebo or oral trapidil 200 mg t.i.d. at least 48 hr before PCI and continuing 6
      months after a successful balloon angioplasty or stent implantation. Aspirin was
      given to all patients, and ticlopidine 250 mg b.i.d. to those who received a
      stent for 4 weeks. In a randomized subgroup of 216 patients, quantitative
      coronary angiography was performed also at 6-month follow-up. Out of the 933
      patients enrolled, primary endpoint incidence was 20.3% in trapidil and 18.0% in
      placebo (P = 0.37). When recurrence or deterioration of angina was added to the
      combined endpoint, incidence was 27.4% in trapidil and 23.0% in placebo (P =
      0.12). Restenosis rate in patients with 6-month angiography was 25.0% in trapidil
      arm vs. 30.1% in placebo (P = 0.43). Stent restenosis rate was similar in
      patients randomized to trapidil or placebo (30.2% vs. 23.8%, respectively; P =
      0.44), while in patients treated with balloon angioplasty, it was lower in
      trapidil (17.1%) than in placebo (40.0%; P = 0.03). Oral trapidil 200 mg t.i.d.
      for 6 months in addition to aspirin did not influence the occurrence of major
      cardiac events after coronary angioplasty with or without stenting. In a
      prespecified subgroup of 191 patients treated with balloon angioplasty only,
      trapidil reduced angiographic restenosis.

PMID- 15736250
TI  - Transcatheter closure of a 22 mm patent ductus arteriosus with an Amplatzer
      atrial septal occluder.
AB  - Transcatheter techniques for closure of patent ductus arteriosus (PDA) have been
      used for almost 40 years. We report a case of a 24-year-old female with a 22 mm
      PDA, congestive heart failure, and atrial fibrillation. She underwent
      transcatheter PDA closure with an Amplatzer atrial septal occluder (ASO).
      Following the procedure, she developed hemolysis due to a large residual shunt.
      However, the shunt gradually resolved until complete closure was achieved within
      8 months. An attempt to restore sinus rhythm with electrical cardioversion was
      successful and the patient is now, 2 years after procedure, in New York Heart
      Association functional class I. Off-label use of an ASO for closure of a very
      large PDA yielded an excellent clinical result.

PMID- 15736251
TI  - Submassive pulmonary embolism and paradoxical embolic stroke treated with
      percutaneous rheolytic thrombectomy and closure of the patent foramen ovale.
AB  - The presence of patent foramen ovale (PFO) in patients with large pulmonary
      emboli (PE) is associated with an increased risk of stroke and mortality. Many
      patients are ineligible to receive thrombolytic therapy. We present a patient
      with bilateral PE and cryptogenic stroke who was treated effectively with
      rheolytic thrombectomy with AngioJet, PFO closure with CardioSeal device, and
      placement of an inferior vena cava filter.

PMID- 15736252
TI  - Left ventricular conditioning in the elderly patient to prevent congestive heart
      failure after transcatheter closure of atrial septal defect.
AB  - Transcatheter closure of atrial septal defects (ASDs) is a safe and effective
      treatment. Over the past years, an increasing number of elderly patients (age >
      60 years) have been admitted for transcatheter closure to prevent ongoing
      congestive heart failure from volume overload. However, recent data point to the
      risk of serious acute left ventricular dysfunction leading to pulmonary edema
      immediately after surgical or transcatheter ASD closure in some patients. In this
      study, we used a technique described before to recognize in advance patients at
      risk of left heart failure after ASD closure. Those patients at risk were then
      treated with preventive conditioning medication for 48-72 hr before definitive
      transcatheter ASD closure was performed. Fifty-nine patients aged over 60 years
      (range, 60-81.8 years; median, 68 years) were admitted to our institution for
      transcatheter closure of an atrial septal defect. All patients received
      evaluation of atrial pressures before and during temporary balloon occlusion of
      the ASD. Patients with left ventricular restriction due to increased mean atrial
      pressures (> 10 mm Hg) during ASD occlusion received anticongestive conditioning
      medication with i.v. dopamine, milrinone, and furosemide for 48-72 hr before
      definitive ASD closure with an Amplatzer septal occluder was performed. In 44
      patients without any signs of left ventricular restriction, ASD closure was
      performed within the first session. Fifteen (25%) out of 59 patients showed left
      ventricular restriction. In the majority of patients with LV restriction, the
      mean left atrial pressures with occluded ASD were significantly decreased after
      48-72 hr of conditioning medication. Definitive ASD closure was then performed in
      a second session. Only two patients received a fenestrated 32 mm Amplatzer
      occluder due to persistent increased atrial pressures > 10 mm Hg even after
      conditioning medication. There were no significant differences in shunt, device
      size, or defect size between the two groups. Balloon occlusion of atrial septal
      defects identifies patients with left ventricular restrictive physiology before
      ASD closure. Intravenous anticongestive conditioning medication seems to be
      highly effective in preventing congestive heart failure after interventional
      closure of an ASD in the elderly patient with a restrictive left ventricle.

PMID- 15736253
TI  - PFO closure, when the going gets tough ...

PMID- 15736254
TI  - Open no tine before its time.

PMID- 15736255
TI  - Percutaneous balloon aortic valvuloplasty: antegrade transseptal vs. conventional
      retrograde transarterial approach.
AB  - Percutaneous balloon aortic valvuloplasty (BAV) has been limited predominantly to
      a palliative treatment for poor surgical candidates with critical aortic stenosis
      and multiple high-risk or comorbid conditions. The most commonly used technique
      for BAV is the retrograde approach, in which the balloon is passed via the
      femoral artery using 12-14 Fr sheaths. We compared an antegrade transseptal
      approach using the Inoue balloon vs. the retrograde transarterial approach using
      conventional balloons. The antegrade group had an improved acute hemodynamic
      outcome, including 20% additional increase of aortic valve area and 20% greater
      reduction of transaortic valve gradient compared to the retrograde approach.
      Preclosure with the Perclose device was used for the 14 Fr venous access sites,
      resulting in immediate hemostasis, minimizing the need for transfusion, and
      diminishing the period of bed rest. The improved acute efficacy and relative ease
      of venous access for the antegrade approach facilitate BAV by eliminating the
      need for large-caliber arterial access sheaths. The antegrade approach also
      incorporates technical elements necessary for percutaneous aortic valve
      replacement and may have expanded applications as an adjunct to this developing
      therapy. The impact of improved acute results on the long-term clinical outcome
      for this patient group will require further study.

PMID- 15736256
TI  - Bilateral carotid angioplasty and stenting.
AB  - Bilateral carotid stenosis is generally treated by staged stenting procedure and
      rarely simultaneously due to concerns about hemodynamic impairment from
      stimulation of the carotid sinus baroreflex (severe bradycardia, hypotension) and
      the risk of cerebral hyperperfusion syndrome. Most of the accounts of bilateral
      carotid stenting are of small series. The aim of this study was to evaluate the
      feasibility and safety of simultaneous bilateral carotid angioplasty and stenting
      (CAS) in comparison with staged procedure. We retrospectively analyzed the
      procedural outcome and complications of bilateral CAS done between February 1995
      and June 2004 in a consecutive series of 57 high-risk patients. Mean age was 64
      +/- 9 years (male, 43; female 14). One hundred fifteen arteries were treated (one
      patient had bilateral internal carotid artery stenosis associated to an ostial
      common carotid artery stenosis). Thirty-nine patients were symptomatic (70%).
      Thirty-six patients had severe coronary artery disease. Seventeen patients
      underwent a simultaneous bilateral CAS (group 1), 40 in a staged manner (group
      2). Among these 40 patients 10 were treated with a time interval of 24 hr, while
      the 30 other ones were treated with a time interval of 2 days to 2 months. A
      neuroprotection device was used in the last 42 patients. There was technical
      success in all patients and transient bradycardia and/or hypotension in 25
      patients (44%). There was no prolonged bradycardia or hypotension. At 30 days, we
      observed in group 1 (simultaneous bilateral CAS) no transient ischemic attack
      (TIA), no minor stroke, one (5.8%) major stroke (hyperperfusion syndrome with
      brain hemorrhage leading to death in a patient under IIb/IIIa inhibitors), one
      myocardial infarction leading to death, and two (11.7%) death/stroke/myocardial
      infarction; in group 2 (staged procedure), two (5%) TIAs, no minor stroke, no
      major stroke, and one (2.5%) hyperperfusion syndrome with rapid recovery. Among
      the 10 patients treated with a time interval of 24 hr, we observed one TIA. Among
      carefully selected patients, bilateral CAS is feasible simultaneously or the day
      after, with a safety and complication rate comparable to that of large published
      series of CAS or endarterectomies in high-risk patients. Nevertheless, careful
      monitoring of the patient, blood pressure, and heart rate is mandatory to avoid
      complications related to hyperperfusion syndrome. Routine use of neuroprotection
      device and meticulous technique should improve the outcomes of bilateral CAS.

PMID- 15736257
TI  - Successful urgent endovascular surgery for symptomatic subclavian artery
      aneurysmal compression of the trachea.
AB  - The purpose of this study is to report the progress of a patient who entered the
      hospital with symptomatic tracheal compression from a large right subclavian
      artery aneurysm that was treated with a self-expanding stent graft. The patient
      was at increased risk for traditional surgery, thus endovascular isolation of the
      aneurysm was felt to be reasonable. A flexible self-expanding stent graft was
      placed via a brachial artery cutdown and common femoral access without
      complication. The symptoms improved and the patient remained asymptomatic at 2
      year follow-up with serial CT scan confirmation of aneurysm regression. This
      unusual case illustrates that endovascular decompression of an aneurysm may have
      some benefit in alleviating subacute symptoms of extrinsic encroachment into
      other vital structures. Technical and clinical success was achieved with the
      stent graft deployment and this seems to be a reasonable alternative to surgery
      in such patients.

PMID- 15736258
TI  - Approaches to correct device malposition in percutaneous PFO closure: anatomical
      and technical implications.
AB  - We describe three patients with initial failure of transcatheter patent foramen
      ovale closure. Two patients had residual defects successfully closed during the
      initial session, and one patient had a persistent shunt, which was corrected at a
      later time. Anatomical and technical considerations and the role of intracardiac
      ultrasound are discussed.

PMID- 15736259
TI  - Rare case of pulmonary arteriovenous fistula simulating residual defect after
      transcatheter closure of patent foramen ovale for recurrent paradoxical embolism.
AB  - We report on a patient suffering from recurrent cerebrovascular events despite
      previous transcatheter closure of persistent foramen ovale (PFO) with a Helex
      occluder. There was evidence of persistent left-to-right atrial shunt shown by
      transesophageal contrast echocardiography and the patient was admitted to our
      institution for interventional closure of the supposed residual defect. However,
      the PFO was completely closed by the device and left pulmonary artery injections
      showed a pulmonary arteriovenous fistula in the left lower lobe. This rare
      malformation may well explain the recurrent paradoxical embolism. Transcatheter
      fistula closure with coils was performed successfully. This case underlines that
      the existence of an isolated pulmonary arteriovenous fistula as a right-to-left
      shunt in patients with cryptogenic stroke should not be overlooked, even if a PFO
      is present and pulmonary arteriovenous fistula is not suggested by the initial
      physical findings or chest X-ray.

PMID- 15736261
TI  - Do the current ACC/AHA guidelines correctly reflect the attitudes and utilization
      of PCI in patients with unprotected left main coronary artery stenosis?

PMID- 15736260
TI  - Closure devices and vascular complications among percutaneous coronary
      intervention patients receiving enoxaparin, glycoprotein IIb/IIIa inhibitors, and
      clopidogrel.
AB  - The objectives of this study were to explore the rate of vascular complications
      using closure devices (CDs) vs. manual compression (MC) among percutaneous
      coronary intervention (PCI) patients receiving enoxaparin, clopidogrel, aspirin,
      and GP IIb/IIIa inhibitors. The Evaluating Enoxaparin Clotting Times (ELECT)
      study enrolled patients receiving enoxaparin, clopidogrel, and GP IIb/IIIa
      inhibitors when necessary. Any approved CD or MC was allowed post-PCI, and
      clinical outcome data were prospectively collected. Four hundred forty-five
      patients had anti-Xa levels measured by a core laboratory and by a novel point-of
      care device that reports ENOX times. All received enoxaparin, aspirin, and
      clopidogrel, and 75% received a concomitant GP IIb/IIIa inhibitor. Major and
      minor bleeding were defined according to TIMI criteria. "Any bleeding" included
      the occurrence of access site complications including hematoma, significant
      rebleeding, or bleeding delaying hospital discharge. TIMI major plus minor
      bleeding occurred in 1.5% of the patients who received CD vs. 1.8% of patients
      with MC (P = 0.83). Any bleeding occurred in 12.2% of CD vs. 5.7% MC (P = 0.02),
      and in 9.5% of patients receiving GP IIb/IIIa inhibitor vs. 2.8% (P = 0.01) among
      those who did not. For patients receiving both a GP IIb/IIIa inhibitor and CD,
      any bleeding was observed in 13.7% vs. 3.4% (P = 0.006) among patients who
      received neither. While minor and major TIMI bleeding remained very low in both
      groups, CD was associated with a twofold increase in risk of any-bleeding event
      when compared to MC, especially when using GP IIb/IIIa inhibitors.

PMID- 15736262
TI  - Randomized comparison between Inoue balloon and metallic commissurotome in the
      treatment of rheumatic mitral stenosis: immediate results and 6-month and 3-year
      follow-up.
AB  - The metallic commissurotome (MC) technique is a cheaper alternative to the Inoue
      balloon (IB) technique for percutaneous mitral valvuloplasty (PMV). There are no
      randomized trials comparing these techniques with longer follow-up of the
      patients. The objective of this study was to compare the immediate results and
      short- and medium-term follow-up of PMV using either the IB or the MC technique.
      Fifty patients with rheumatic mitral stenosis were randomly assigned to PMV using
      the IB (n = 27) or the MC (n = 23) technique. There were no significant
      differences between the groups regarding baseline clinical, echocardiographic,
      and hemodynamic data. Clinical and echocardiographic follow-up were done 6 months
      and 3 years after the procedure. The success rate was 100% in the IB group and
      91.3% in the MC group (P = 0.15); two patients in the latter group developed
      mitral regurgitation grade 3/4, requiring elective surgery. The mean final mitral
      valve area was bigger in the MC group (2.17 +/- 0.13 vs. 2.00 +/- 0.36 cm2; P =
      0.04), but after 6-month and 3-year follow-up, this difference was no longer
      significant (2.06 +/- 0.27 vs. 1.98 +/- 0.38 cm2, P = 0.22, and 1.86 +/- 0.32 vs.
      1.87 +/- 0.34 cm2, P = 0.89, respectively). This finding suggests valve
      stretching as an important mechanism of valve dilation with the MC. Three
      patients in the MC group and two patients in the IB group (P = 0.65) developed
      mitral valve restenosis; one of them underwent repeat PMV and the other four, all
      asymptomatic, were clinically followed. PMV performed either with the IB or the
      MC technique is effective and provides excellent short- and medium-term outcomes
      regardless of the technique employed.

PMID- 15736263
TI  - Transcatheter creation of atrial septal perforation using a radiofrequency
      transseptal system: novel approach as an alternative to transseptal needle
      puncture.
AB  - Indications for the transseptal approach to the left side of the heart have
      recently broadened, as it provides a therapeutic access for both left-sided
      catheter ablation and also percutaneous transvenous valvular intervention.
      Despite rising demand for transseptal procedures, the technique and device used
      for this purpose have remained essentially unchanged over the past 4 decades. The
      possibilities of failure of puncturing distorted and thickened atrial septal
      tissue or risks of complications related to cardiac perforation remain
      limitations of the technique. A new radiofrequency catheter provides an
      alternative approach to create a controlled transseptal perforation. We applied
      this technique to a series of patients and evaluated its feasibility as an
      alternative to conventional transseptal needle puncture.

PMID- 15736264
TI  - Generation of a floxed allele of the mouse BMP type II receptor gene.
AB  - Bone morphogenetic proteins (BMPs) regulate a wide range of cellular functions
      that contribute to embryonic development from mesoderm formation to
      organogenesis. BMP type II receptor (BMPR-II) transduces BMP signals by forming
      heteromeric complexes with and phosphorylating BMP type I receptors. Heterozygous
      germline mutations of BMPR-II gene have been identified in patients with familial
      and sporadic primary pulmonary hypertension, indicating that BMPR-II may
      contribute to the maintenance of normal pulmonary vascular structure and
      function. Since embryos homozygous for a null BMPR-II allele died during
      gastrulation, precluding further studies of BMPR-II function in organ formation
      and in adult tissues, we generated mice carrying a conditional mutant BMPR-II
      allele in which exons 4 and 5 were flanked by loxP sequences. We anticipate that
      studies of mice carrying a floxed BMPR-II allele and a Cre transgene (under the
      control of a tissue-specific promoter) will enable characterization of the role
      of BMPR-II in specific cell types during development and in the pathogenesis of
      cardiovascular diseases.

PMID- 15736265
TI  - Endovascular treatment of basilar artery stenosis with drug-eluting stent: a case
      report and literature review.
AB  - Symptomatic basilar artery stenosis can be treated with stents. However, it still
      has limitations such as technical difficulty and restenosis. We describe a 61
      year-old man with episodic vertigo and significant basilar artery stenosis, who
      was successfully treated with drug-eluting stent. At 6 month follow-up, cerebral
      angiography revealed patent basilar artery.

PMID- 15736266
TI  - Characterization of Opr deficiency in mouse brain: subtle defects in dorsomedial
      telencephalon and medioventral forebrain.
AB  - Opr/Zic5 is a zinc-finger gene belonging to, and unique in, the opa/Zic family.
      Its expression is found in the anterior epiblast and anterior neuroectoderm
      during gastrulation and early neurulation. Later, we found the expression
      characteristic in the dorsomedial parts of forebrain and midbrain. However, no
      defects were apparent in embryonic day 10.5 Opr null mutants, and subtle defects
      were later found in medial pallium and ventral structures of forebrain,
      suggesting the compensation of Opr deficiency by its cognate(s).

PMID- 15736267
TI  - XTbx1 is a transcriptional activator involved in head and pharyngeal arch
      development in Xenopus laevis.
AB  - The development of pharyngeal arch derivatives in mouse and zebrafish embryos
      depends on the activity of the transcription factor Tbx1. We cloned the Xenopus
      laevis orthologue of Tbx1 (XTbx1) and show that the pattern of expression is
      similar to that in other vertebrate species. Zygotic transcripts are first
      detected shortly after the mid-blastula transition and are localized to the
      presumptive mesoderm at mid-gastrula stages. XTbx1 expression persists in the
      lateral plate mesoderm at neurula stages and is found in the pharyngeal arches
      and otic vesicles from early tail bud stages onward. We demonstrate that XTbx1 is
      a transcriptional activator and that this trans-activation requires the C
      terminal region of the protein. A dominant interfering mutant of XTbx1 disrupts
      the development of Xenopus head structures and pharyngeal arch derivatives.
      Lineage labeling reveals a requirement for XTbx1 function in cells that
      contribute to the pharyngeal mesoderm and for fgf8 expression.

PMID- 15736269
TI  - Ectopic expression of KitD814Y in spermatids of transgenic mice, interferes with
      sperm morphogenesis.
AB  - Kit is a receptor tyrosine kinase that plays a fundamental role during the
      development of germ cells. Additionally, a truncated product, tr-kit, expressed
      in haploid spermatids and mature spermatozoa can induce parthenogenetic
      activation when microinjected into mouse eggs, through the activation of PLCgamma
      1. In this work, we induced ectopic expression of a mutated Kit protein,
      Kit(D814Y) during germ cell development. The in vivo expression of this mutant in
      spermatids produced malformations in mature spermatozoa, and in the most severe
      cases, sterility. Ultrastructural analysis indicated that condensing spermatids
      in the transgenic mouse presented a mislocalization of the manchette; a structure
      that has a crucial role during the elongation steps of spermiogenesis. This
      morphogenetic phenotype was accompanied by an increased phosphorylation of
      PLCgamma-1 in spermatogenic cells. Interestingly, we also found that, in wild
      type testis, PLCgamma-1 is specifically phosphorylated in condensing spermatids,
      coincident with the timing of expression of tr-kit in spermiogenesis. We propose
      that alterations of PLCgamma-1 activity artificially promoted by ectopic
      Kit(D814Y) expression are related to the abnormalities of spermiogenesis. Our
      observations suggest that PLCgamma-1 activity could be involved in the shaping of
      spermatozoa.

PMID- 15736270
TI  - Confidence limits for the ratio of two rates based on likelihood scores: non
      iterative methods by P. L. Graham, K. Mengersen and A. P. Morton, Statistics in
      Medicine 2003; 22:2071-2083.

PMID- 15736271
TI  - Catchlike property of skeletal muscle: recent findings and clinical implications.
AB  - The catchlike property of skeletal muscle is the force augmentation produced by
      the inclusion of an initial, brief, high-frequency burst of two to four pulses at
      the start of a subtetanic low-frequency stimulation train. Catchlike-inducing
      trains take advantage of the catchlike property of skeletal muscle and augment
      muscle performance compared with constant-frequency trains, especially in the
      fatigued state. Literature spanning more than 30 years has provided comprehensive
      information about the catchlike property of skeletal muscle. The pattern of the
      catchlike-inducing train that maximizes muscle performance is fairly similar
      across different muscles of different species and under various stimulation
      conditions. This review summarizes the mechanisms of the catchlike property,
      factors affecting force augmentation, techniques used to identify patterns of
      catchlike-inducing trains that maximize muscle performance, and potential
      clinical applications to provide a historical and current perspective of our
      understanding of the catchlike property.

PMID- 15736273
TI  - An experimental and computational study on the effect of Al(OiPr)3 on atom
      transfer radical polymerization and on the catalyst-dormant-chain halogen
      exchange.
AB  - Compound Al(OiPr)3 is shown to catalyze the halide-exchange process leading from
      [Mo(Cp)Cl2(iPrN=CH-CH=NiPr)] and CH3CH(X)COOEt (X=Br, I) to the mixed-halide
      complexes [Mo(Cp)ClX(iPrN=CH-CH=NiPr)]. On the other hand, no significant
      acceleration is observed for the related exchange between [MoX3(PMe3)3] (X=Cl, I)
      and PhCH(Br)CH3, by analogy to a previous report dealing with the Ru(II) complex
      [RuCl2(PPh3)3]. A DFT computation study, carried out on the model complexes
      [Mo(Cp)Cl2(PH3)2], [MoCl3(PH3)3], and [RuCl2(PH3)3], and on the model initiators
      CH3CH(Cl)COOCH3, CH3Cl, and CH3Br, reveals that the 16-electron Ru(II) complex is
      able to coordinate the organic halide RX in a slightly exothermic process to
      yield saturated, diamagnetic [RuCl2(PH3)3(RX)] adducts. The 15-electron
      [MoCl3(PH3)3] complex is equally capable of forming an adduct, that is, the 17
      electron [MoCl3(PH3)3(CH3Cl)] complex with a spin doublet configuration, although
      the process is endothermic, because it requires an energetically costly electron
      pairing process. The interaction between the 17-electron [Mo(Cp)Cl2(PH3)2]
      complex and CH3Cl, on the other hand, is repulsive and does not lead to a stable
      19-electron adduct. The [RuCl2(PH3)3(CH3X)] system leads to an isomeric complex
      [RuClX(PH3)3(CH3Cl)] by internal nucleophilic substitution at the carbon atom.
      The transition state of this process for X=Cl (degenerate exchange) is located at
      lower energy than the transition state required for halogen-atom transfer leading
      to [RuCl3(PH3)3] and the free radical CH3. On the basis of these results, the
      uncatalyzed halide exchange is interpreted as the result of a competitive S(N)i
      process, whose feasibility depends on the electronic configuration of the
      transition-metal complex. The catalytic action of Al(OiPr)3 on atom-transfer
      radical polymerization (and on halide exchange for the 17-electron half-sandwich
      Mo(III) complex) results from a more favorable Lewis acid-base interaction with
      the oxidized metal complex, in which the transferred halogen atom is bound to a
      more electropositive element. This conclusion derives from DFT studies of the
      model [Al(OCH3)3]n (n=1,2,3,4) compounds, and on the interaction of Al(OCH3)3
      with CH3Cl and with the [Mo(Cp)Cl3(PH3)2] and [RuCl3(PH3)3] complexes.

PMID- 15736272
TI  - Skinned single fibers from normal and dystrophin-deficient dogs incur comparable
      stretch-induced force deficits.
AB  - Intact dystrophin-deficient canine muscles were previously shown to incur greater
      than-normal stretch-induced force deficits. Here we tested the hypothesis that
      maximally activated detergent-treated (skinned) single fibers from normal and
      dystrophin-deficient dogs would incur comparable force deficits after stretch.
      Skinned cranial sartorius (CS) fibers from dystrophin-deficient and normal dogs
      were calcium-activated (pCa 4.5) and rapidly stretched. A single 30% stretch
      induced force deficits of 27.07 +/- 3.9% and 29.7 +/- 4.8% in dystrophin
      deficient (n = 22) and normal (n = 18) fibers, respectively. Our data support the
      hypothesis that maximally activated skinned single fibers from normal and
      dystrophin-deficient dogs incur comparable force deficits after stretch. Our
      findings suggest that knowledge of the extent of stretch-induced force deficits
      following repeated stretch-activations in the GRMD dog may be useful to assess
      future therapeutic interventions aimed at replacing dystrophin in the sarcolemmal
      membrane.

PMID- 15736274
TI  - Self-assembled nanotapes of oligo(p-phenylene vinylene)s: sol-gel-controlled
      optical properties in fluorescent pi-electronic gels.
AB  - A rational approach to the design of supramolecular organogels of all-trans
      oligo(p-phenylene vinylene) (OPV) derivatives, a class of well-known organic
      semiconductor precursors, is reported. Self-assembly of these molecules induced
      gelation of hydrocarbon solvents at low concentrations (<1 mM), resulting in high
      aspect ratio nanostructures. Electron microscopy and atomic force microscopy
      (AFM) studies revealed twisted and entangled supramolecular tapes of an average
      of 50-200 nm in width, 12-20 nm in thickness, and several micrometers in length.
      The hierarchical growth of the entangled tapes and the consequent gelation is
      attributed to the lamellar-type packing of the molecules, facilitated by
      cooperative hydrogen bonding, pi stacking, and van der Waals interactions between
      the OPV units. Gelation of OPVs induced remarkable changes in the absorption and
      emission properties, which indicated strong electronic interaction in the
      aggregated chromophores. Comparison of the absorption and emission spectra in the
      gel form and in the solid film indicated a similar chromophore organization in
      both phases. The presence of self-assembled aggregates of OPVs was confirmed by
      solvent- and temperature-dependent changes in the absorption and emission
      properties, and by selective excitation experiments. This is the first detailed
      report of the gelation-induced formation of OPV nanotapes, assisted by weak,
      nondirectional hydrogen-bonding motifs and pi-pi stacking. These findings may
      provide opportunities for the design of a new class of functional soft materials
      and nanoarchitectures, based on pi-conjugated organic semiconductor-type
      molecules, thereby enabling the manipulation of their optical properties.

PMID- 15736275
TI  - Efficient solid-phase synthesis of highly functionalized 1,4-benzodiazepin-5-one
      derivatives and related compounds by intramolecular aza-Wittig reactions.
AB  - Due to their widespread biological activities and favorable pharmacokinetic
      properties, benzodiazepines were among the first classes of small molecules to be
      synthesized on solid supports. Since then, there have been numerous reports on
      the synthesis of similar skeletons. We have employed the T1 triazene linker to
      yield 1,4-benzodiazepin-5-one. Starting from various substituted triazene resins,
      cleavage in the presence of an azide donor, such as trimethylsilylazide, gave
      rise to aryl azides. Intramolecular aza-Wittig reactions produced the
      appropriately functionalized N-heterocycles. By using this route, the natural
      product deoxyvasicinone and related compounds were prepared.

PMID- 15736276
TI  - Can weakly coordinating anions stabilize mercury in its oxidation state +IV?
AB  - While the thermochemical stability of gas-phase HgF4 against F2 elimination was
      predicted by accurate quantum chemical calculations more than a decade ago,
      experimental verification of "truly transition-metal" mercury(IV) chemistry is
      still lacking. This work uses detailed density functional calculations to explore
      alternative species that might provide access to condensed-phase Hg(IV)
      chemistry. The structures and thermochemical stabilities of complexes Hg(IV)X4
      and Hg(IV)F2X2 (X- = AlF4-, Al2F7-, AsF6-, SbF6-, As2F11-, Sb2F11-, OSeF5-, OTeF5
      ) have been assessed and are compared with each other, with smaller gas-phase
      HgX4 complexes, and with known related noble gas compounds. Most species
      eliminate F2 exothermically, with energies ranging from only about -60 kJ mol(-1)
      to appreciable -180 kJ mol(-1). The lower stability of these species compared to
      gas-phase HgF4 is due to relatively high coordination numbers of six in the
      resulting Hg(II) complexes that stabilize the elimination products. Complexes
      with AsF6 ligands appear more promising than their SbF6 analogues, due to
      differential aggregation effects in the Hg(II) and Hg(IV) states. HgF2X2
      complexes with X- = OSeF5- or OTeF5- exhibit endothermic fluorine elimination and
      relatively weak interactions in the Hg(II) products. However, elimination of the
      peroxidic (OEF5)2 coupling products of these ligands provides an alternative
      exothermic elimination pathway with energies between -120 and -130 kJ mol(-1).
      While all of the complexes investigated here thus have one exothermic
      decomposition channel, there is indirect evidence that the reactions should
      exhibit nonnegligible activation barriers. A number of possible synthetic
      pathways towards the most interesting condensed-phase Hg(IV) target complexes are
      proposed.

PMID- 15736277
TI  - Ligand functionality as a versatile tool to control the assembly behavior of
      preformed titania nanocrystals.
AB  - Nanoparticle powders composed of surface-functionalized anatase crystals with
      diameters of about 3 nm self-organize into different structures upon redispersion
      in water. The assembly is directed by a small amount of a low-molecular-weight
      functional ligand (the "assembler") adsorbed on the surface of the nanoparticles.
      The ligand functionality determines the anisotropy of the resulting structures.
      Multidentate ligands, such as trizma ((HOCH(2))(3)CNH(2)) and serinol
      ((HOCH(2))(2)CNH(2)), with a chargeable terminal group preferentially induce the
      formation of anisotropic nanostructures several hundreds of nanometers in total
      length, whereas all the other investigated ligands (ethanolamine
      H(2)N(CH(2))(2)OH, glycine hydroxamate H(2)NCH(2)CONHOH, dopamine
      (OH)(2)C(6)H(3)(CH(2))(2)NH(3)Cl, tris (HOCH(2))(3)CCH(3)) mainly lead to
      uncontrolled agglomeration. Experimental data suggests that the anisotropic
      assembly is a consequence of the water-promoted desorption of the organic ligands
      from the {001} faces of the crystalline building blocks together with the
      dissociative adsorption of water on these crystal faces. Both processes induce
      the preferred attachment of the titania nanoparticles along the [001] direction.
      The use of polydentate and charged ligands to functionalize the surface of
      nanoparticles thus provides a versatile tool to control their arrangement on the
      nanoscale.

PMID- 15736278
TI  - Structural analysis of chiral complexes of palladium(0) with 15-membered
      triolefinic macrocyclic ligands.
AB  - The complete structural analysis of the palladium complexes of the triolefinic
      macrocycles (E,E,E)-1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3,8,13
      trienes, which featured from three identical to three different aryl groups, was
      achieved by performing X-ray diffraction studies, NMR spectroscopy, and other
      calculations. The stereochemical complexity is determined by the different
      isomers formed through complexation of the metal to one or other face of each of
      the three olefins involved. The palladacyclopropane formulation of the palladium
      olefin interaction offers a clear picture of the stereogenicity of the olefin
      carbon atoms that are complexed to the metal. The energetically favorable isomers
      were identified in the solid-state and in solution by performing X-ray
      diffraction and NMR spectroscopic analysis, respectively.

PMID- 15736279
TI  - The effects of joint misclassification of exposure and disease on the
      attributable risk.
AB  - While there is extensive methodological literature analysing the effects of
      misclassification on the relative risk under various misclassification scenarios,
      for the attributable risk only the effects of non-differential misclassification
      either of exposure or disease, and the effects of non-differential independent
      misclassification of exposure and disease have been discussed for the 2 x 2
      situation. The paper investigates the effects of non-differential correlated
      misclassification of exposure and disease on the attributable risk taking
      possible correlations of both types of misclassification into account.
      Furthermore, a comparison with the corresponding effects on the relative risk is
      drawn. We propose a matrix-based approach to describe the underlying structure of
      non-differential misclassification. The bias arising from non-differential
      misclassification in the attributable risk and relative risk is evaluated in four
      examples assuming under- or overreporting of exposure and disease. In each of the
      four examples we found scenarios where pronounced differences in degree and, more
      importantly, in direction of bias occurred. Our results clearly demonstrate the
      danger lying in the stereotype transfer of findings regarding misclassification
      effects on the relative risk to other epidemiologic risk measures and underline
      the necessity of specific analyses of the effects of misclassification on the
      attributable risk.

PMID- 15736280
TI  - Prediction of heterofullerene stabilities: a combined DFT and chemometric study
      of C56Pt2, C57Pt2 and C81Pt2.
AB  - A systematic search of the regioisomers of the heterofullerenes, C57Pt2 and
      C56Pt2, has been carried out by means of density functional calculations to find
      the most stable structures. Both heterofullerenes incorporate two metal atoms
      into the fullerene surface. In the case of C57Pt2, one platinum atom substitutes
      one carbon atom of C60 and the other platinum atom replaces a C--C bond, whereas
      in C56Pt2 each platinum atom replaces one C--C bond. Several geometric factors
      were studied, three of which have particularly important effects on the relative
      stabilities of the regioisomers: the Pt--Pt separation, the number of C--C bonds
      remaining after substitution, and the type of C--C bond that is substituted. All
      these factors indicate that the deformation of the carbon framework is a general
      factor that governs the relative stabilities of the regioisomers. Because a high
      number of factors affect the stability of the heterofullerenes we also used
      chemometric techniques in this study. Partial least-squares (PLS) regression was
      used to establish the structure-energy relationships of C57Pt2 and C56Pt2
      heterofullerenes. The understanding gained of the factors that affect the
      relative isomers stabilities has allowed us to predict the stabilities of larger
      disubstituted carbon cages, for example, C81Pt2 heterofullerene.

PMID- 15736281
TI  - Interval estimation of the difference in proportions under m-to-one matching.
AB  - When the number of potential controls is large relative to the number of
      available cases, or when little effort needs to be expended in collecting the
      relevant information on the controls, we often apply multiple matching to attain
      the validity or increase the efficiency of our inference in epidemiological
      studies. In this paper, we focus interval estimation on the difference in
      proportions for m-to-one matching. We consider four asymptotic interval
      estimators, including the estimator directly using the Mantel-Haenszel (MH) point
      estimator, the estimator using the tanh(-1)(x) transformation, the estimator
      derived from the Cochran-Mantel-Haenszel (CMH) test statistic, and the estimator
      derived from the quadratic inequality developed in this paper. To evaluate and
      compare the performance of these estimators, we employ Monte Carlo simulation. We
      find that the estimator directly using the MH estimator can have the coverage
      probability less than the desired confidence level when the number of matched
      sets is small. We note that the estimator derived from the quadratic inequality
      can perform well when the underlying difference is close to 0 even for a small
      number of matched sets. However, this estimator tends to have the coverage
      probability less than the desired confidence level as well when the underlying
      difference in proportions is large. By contrast, the estimator using the CMH
      statistic tends to have the coverage probability larger than the desired
      confidence level when the underlying difference is small. We also find that the
      estimator using the tanh(-1)(x) transformation consistently outperforms the
      interval estimator directly using the MH estimator. We use the data regarding the
      association between induced abortions and ectopic pregnancy to illustrate the use
      of these estimators.

PMID- 15736282
TI  - Nanocap-shaped tin phthalocyanines: synthesis, characterization, and corrosion
      inhibition activity.
AB  - Thermal and microwave reactions between [PcSn(IV)Cl2] (1) and the potassium salts
      of eight fatty acids (2 a-h) led to cis-[(RCO2)2Sn(IV)Pc] compounds (3 a-h) in
      yields ranging from 54 to 90 %. Compounds 3 a-h were fully characterized by
      elemental analysis, spectroscopy (IR, UV/Vis, multinuclear NMR), and seven X-ray
      diffraction structures, whereby two different allotropes were observed in two
      cases. The two carboxylates in 3 have a cis anisobidentate binding mode,
      octacoordination of the tin atoms with square-antiprismatic geometry, and pi
      electron-rich nanocap shapes. On account of the latter characteristics, 3 a-h
      compounds have anticorrosion properties. LPR and Tafel electrochemical methods
      were used to characterize the behavior of these derivatives in naturally aerated
      sour brine, which is a common environment in petroleum production and refinery
      operations. The measurement of the corrosion rate of carbon steel AISI 1018 in
      the presence of 3 a-h (500 ppm) gave efficiencies of 61-87 % for the inhibitor
      performance. Of the different derivatives examined, compounds 3 e and 3 h were
      the most effective corrosion inhibitor prototypes.

PMID- 15736283
TI  - Correlated errors in biased surrogates: study designs and methods for measurement
      error correction.
AB  - A measurement error model proposed previously allows for correlations between
      subject-specific biases and between random within-subject errors in the
      surrogates obtained from two modes of measurement. However, most of these model
      parameters are not identifiable from the standard validation study design,
      including, importantly, the attenuation factor needed to correct for bias in
      relative risk estimates due to measurement error. We propose validation study
      designs that permit estimation and inference for the attenuation factor and other
      parameters of interest when these correlations are present. We use an estimating
      equations framework to develop semi-parametric estimators for these parameters,
      exploiting instrumental variables techniques. The methods are illustrated through
      application to data from the Nurses' Health Study and Health Professionals'
      Follow-up Study, and comparisons are made to more restrictive models.

PMID- 15736284
TI  - New oxadiazole derivatives showing partly antiplatelet, antithrombotic and
      serotonin antagonistic properties.
AB  - Ten new 1, 2, 4-oxadiazole- and six new 1, 3, 4-oxadiazole-carboxamides
      containing different lipophilic moieties (i.e. 4-biphenyl-, 1-naphthyl,
      phenylpropyl- and n-hexyl substituents) and additional basic groups which are
      mainly alkyl- and dialkylaminoalkyl residues have been synthesized and tested for
      antiplatelet effects in vitro (Born-test) and antithrombotic properties in vivo
      (laser thrombosis model). If the platelet aggregation was induced by collagen,
      the inhibitory effects (IC50) were between 58 microM and 300 microM. Using
      serotonin (5-HT) as an inducer, compound 6a (N-(3-dimethylaminopropyl-5-(biphenyl
      4-yl)-1, 3, 4-oxadiazole-2-carboxamide) had an IC50 = 1 microM (12e: (N-3
      Dimethylaminopropyl)-3-(1-naphthyl)-1, 2, 4-oxadiazole-5-carboxamide, 6.7
      microM). In an in vitro rat tail artery assay 6a and 12e behaved as a competitive
      5-HT2A receptor antagonist (6a: pKB = 6.86 +/- 0.04; 12e: pKB = 6.66 +/- 0.05).
      The antithrombotic effects of some compounds were small but significant (7-10 %
      inhibition of thrombus formation).

PMID- 15736285
TI  - Evaluation of some pyrazoloquinolines as inhibitors of herpes simplex virus type
      1 replication.
AB  - Three structurally related aminopyrazoloquinoline derivatives were evaluated for
      their antiviral activity against Herpes Simplex virus type 1. These compounds
      were examined for their in vitro antiviral activity by two different bioassays,
      namely; crystal violet staining and tetrazolium dye (MTS) measurement. The
      antiviral role of these compounds was confirmed by enumerating the infectious
      particles with plaque assay. The acute toxicity values of the biologically active
      compounds were determined prior to their screening as antiviral agents.

PMID- 15736286
TI  - Stability and effectiveness against bacterial adhesion of poly(ethylene oxide)
      coatings in biological fluids.
AB  - Poly(ethylene oxide) (PEO) coatings have been shown to reduce the adhesion of
      different microbial strains and species and thus are promising as coatings to
      prevent biomaterial-centered infection of medical implants. Clinically, however,
      PEO coatings are not yet applied, as little is known about their stability and
      effectiveness in biological fluids. In this study, PEO coatings coupled to a
      glass substratum through silyl ether bonds were exposed for different time
      intervals to saliva, urine, or phosphate-buffered saline (PBS) as a reference at
      37 degrees C. After exposure, the effectiveness of the coatings against bacterial
      adhesion was assessed in a parallel plate flow chamber. The coatings appeared
      effective against Staphylococcus epidermidis adhesion for 24, 48, and 0.5 h in
      PBS, urine, and saliva, respectively. Using XPS and contact-angle measurements,
      the variations in effectiveness could be attributed to conditioning film
      formation. The overall short stability results from hydrolysis of the coupling of
      the PEO chains to the substratum.

PMID- 15736288
TI  - Effect of porosity on the fluid flow characteristics and mechanical properties of
      tantalum scaffolds.
AB  - In many cases of traumatic bone injury, bone grafting is required. The primary
      source of graft material is either autograft or allograft. The use of both
      material sources are well established, however, both suffer limitations. In
      response, many grafting alternatives are being explored. This article
      specifically focuses on a porous tantalum metal grafting material (Trabecular
      Metaltrade mark) marketed by Zimmer. Twenty-one cylindrical scaffolds were
      manufactured (66% to 88% porous) and tested for porosity, intrinsic permeability,
      tangent elastic modulus, and for yield stress and strain behavior. Scaffold
      microstructural geometries were also measured. Tantalum scaffold intrinsic
      permeability ranged from 2.1 x 10(-10) to 4.8 x 10(-10) m(2) and tangent elastic
      modulus ranged from 373 MPa to 2.2 GPa. Both intrinsic permeability and tangent
      elastic modulus closely matched porosity-matched cancellous bone specimens from a
      variety of species and anatomic locations. Scaffold yield stress ranged from 4 to
      12.7 MPa and was comparable to bovine and human cancellous bone. Yield strain was
      unaffected by scaffold porosity (average = 0.010 mm/mm). Understanding these
      structure-function relationships will help complete the basic physical
      characterization of this new material and will aid in the development of
      realistic mathematical models, ultimately enhancing future implant designs
      utilizing this material.

PMID- 15736287
TI  - Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix
      and contains porcine DNA: possible implications in human implantation.
AB  - Porcine small intestinal submucosa (SIS) has been recommended as a cell-free,
      biocompatible biomaterial for the repair of rotator cuff tendon tear. However, we
      have observed noninfectious edema and severe pain in patients who have undergone
      SIS implantation for tendon repair. The aim of this study was to conduct an
      independent assessment of the safety and efficacy of Restore SIS membrane. The
      Restore orthobiologic implant was examined by histology and the nested PCR
      technique using porcine immunoreceptor DAP12 gene to examine if SIS membrane
      contained porcine cells or DNA, respectively. The material was also implanted
      into mice and rabbits for the evaluation of biological reaction and inflammatory
      response. Restore SIS was found to contain multiple layers of porcine cells.
      Chloroacetate esterase staining showed that some of these cells were mast cells.
      Nested PCR of the DAP12 gene demonstrated that Restore SIS contained porcine DNA
      material. Subcutaneous implantation of Restore SIS membrane in mice, and in
      rabbits for rotator cuff tendon repair, showed that the membrane caused an
      inflammatory reaction characterized by massive lymphocyte infiltration. In
      conclusion, Restore SIS is not an acellular collagenous matrix, and contains
      porcine DNA. Our results contradict the current view that Restore SIS is a cell
      free biomaterial, and that no inflammatory response is elicited by its
      implantation. We suggest that further studies should be conducted to evaluate the
      clinical safety and efficacy of SIS implant biomaterials.

PMID- 15736290
TI  - Preventing microalbuminuria in type 2 diabetes.

PMID- 15736291
TI  - Telmisartan vs. enalapril in type 2 diabetes.

PMID- 15736292
TI  - Telmisartan vs. enalapril in type 2 diabetes.

PMID- 15736293
TI  - Prostanoid DP receptor variants and asthma.

PMID- 15736294
TI  - Medical research and the news media.

PMID- 15736295
TI  - Multiple myeloma.

PMID- 15736296
TI  - Multiple myeloma.

PMID- 15736297
TI  - Persistent inward currents in motoneuron dendrites: implications for motor
      output.
AB  - The dendrites of motoneurons are not, as once thought, passive conduits for
      synaptic inputs. Instead they have voltage-dependent channels that provide the
      capacity to generate a very strong persistent inward current (PIC). The amplitude
      of the PIC is proportional to the level of neuromodulatory input from the
      brainstem, which is mediated primarily by the monoamines serotonin and
      norepinephrine. During normal motor behavior, monoaminergic drive is likely to be
      moderately strong and the dendritic PIC generates many of the characteristic
      features of motor unit firing patterns. Most of the PIC activates at or below
      recruitment threshold and thus motor unit firing patterns exhibit a linear
      increase just above recruitment. The dendritic PIC allows motor unit
      derecruitment to occur at a lower input level than recruitment, thus providing
      sustained tonic firing with little or no synaptic input, especially in low
      threshold units. However the dendritic PIC can be readily deactivated by synaptic
      inhibition. The overall amplification due to the dendritic PIC and other effects
      of monoamines on motoneurons greatly increases the input-output gain of the motor
      pool. Thus the brainstem neuromodulatory input provides a mechanism by which the
      excitability of motoneurons can be varied for different motor behaviors. This
      control system is lost in spinal cord injury but PICs nonetheless recover near
      normal amplitudes in the months following the initial injury. The relationship of
      these findings to the cause of the spasticity syndrome developing after spinal
      cord injury is discussed.

PMID- 15736298
TI  - Statistical motor number estimation assuming a binomial distribution.
AB  - The statistical method of motor unit number estimation (MUNE) uses the natural
      stochastic variation in a muscle's compound response to electrical stimulation to
      obtain an estimate of the number of recruitable motor units. The current method
      assumes that this variation follows a Poisson distribution. We present an
      alternative that instead assumes a binomial distribution. Results of computer
      simulations and of a pilot study on 19 healthy subjects showed that the binomial
      MUNE values are considerably higher than those of the Poisson method, and in
      better agreement with the results of other MUNE techniques. In addition,
      simulation results predict that the performance in patients with severe motor
      unit loss will be better for the binomial than Poisson method. The adapted method
      remains closer to physiology, because it can accommodate the increase in
      activation probability that results from rising stimulus intensity. It does not
      need recording windows as used with the Poisson method, and is therefore less
      user-dependent and more objective and quicker in its operation. For these
      reasons, we believe that the proposed modifications may lead to significant
      improvements in the statistical MUNE technique.

PMID- 15736299
TI  - Muscle regeneration, inflammation, and connective tissue expansion in canine
      inflammatory myopathy.
AB  - Inflammatory myopathies (IMs) are relatively common in dogs, and canine IMs have
      many similarities to human IMs. The aim of this work was to analyze aspects of
      the pathogenesis of canine IM with an ultimate goal of establishing canine IM as
      a model for human IM. Muscle biopsies from 16 dogs with a histological diagnosis
      of IM were analyzed to determine degree of muscle regeneration, presence of
      eosinophils, expression of selected cytokines and chemokines, and extent of
      fibrosis. Regeneration, as shown by staining for developmental myosin heavy
      chain, was more extensive than evidenced with hematoxylin-eosin staining in most
      cases of canine IM. Expression of mRNA encoding transforming growth factor-beta
      (TGF-beta) and eotaxin 3 was upregulated in all cases evaluated. Eosinophils were
      abundant in most cases, and the connective tissue was variably expanded, as
      demonstrated by the distribution of the ubiquitous extracellular matrix proteins
      collagen VI and fibrillin. The extensive regeneration demonstrates that muscle
      may survive this adverse environment if inflammation and fibrosis can be stopped
      or reduced.

PMID- 15736300
TI  - Enrichment of the R77C alpha-sarcoglycan gene mutation in Finnish LGMD2D
      patients.
AB  - Limb-girdle muscular dystrophy 2D (LGMD2D) is caused by mutations in the alpha
      sarcoglycan gene (SGCA). The most frequently reported mutation, 229CGC>TGC (R77C)
      in exon 3 of SGCA, results in the substitution of arginine by cysteine. We
      present here the clinical, immunohistochemical, and genetic data of 11 Finnish
      patients with LGMD2D caused by mutations in SGCA. Mutational analysis showed 10
      patients homozygous and 1 compound heterozygous for R77C. A wide spectrum of SGCA
      mutations has been reported previously. Our results show an enrichment of R77C in
      Finland, further underlined by the observed carrier frequency of 1 per 150.
      According to the annual birth rate of approximately 60,000 in Finland, one LGMD2D
      patient with a homozygous mutation is expected to be born every 1 or 2 years on
      average. The presence of an ancient founder mutation is indicated by the fact
      that all patients shared a short common haplotype extending > or = 790 kilobases.
      Our results emphasize the need to include the SGCA gene R77C mutation test in
      routine DNA analyses of severe dystrophinopathy-like muscular dystrophies in
      Finland, and suggest that the applicability of this test in other populations
      should be studied as well.

PMID- 15736301
TI  - Successful intramuscular neurotization is dependent on the denervation period. A
      histomorphological study of the gracilis muscle in rats.
AB  - To characterize the extent to which reinnervation potential depends on the
      duration of denervation, intramuscular neurotization of the gracilis muscle was
      performed either immediately or 2, 4, 6, and 8 weeks after transection of the
      obturator nerve. For neurotization, the sciatic nerve was split into three
      fascicle groups and fixed intramuscularly. Muscle morphology after 6 weeks of
      regeneration was identified with anti-myosin immunohistochemistry and NADH
      staining. Newly formed motor endplates were characterized using
      acetylcholinesterase staining and electron microscopy. Wet muscle weight ratio
      indicated the functional state of synapses. Depending on the denervation period,
      three levels of regenerative outcome were evident. Best results were seen after
      immediate neurotization or after 2 weeks of denervation. Regeneration, although
      at a significantly lower level, also occurred after denervation periods of 4 and
      6 weeks. Regeneration following neurotization after 8 weeks of denervation was
      negligible. Quantity and quality of motor endplate formation depended on the
      denervation period. Thus, in special clinical situations intramuscular
      neurotization within a distinct time window provides a good reconstructive
      option.

PMID- 15736302
TI  - Protecting the privacy of human subjects.

PMID- 15736303
TI  - Prognostic value of chronic obstructive pulmonary disease in 2994 cases of lung
      cancer.
AB  - OBJECTIVE: Given the frequent association between chronic obstructive pulmonary
      disease (COPD) and lung cancer (LC), the objective of this paper is to analyse
      the prognosis of this comorbidity. METHODS: Multicenter prospective study
      compiling 2994 consecutive cases of surgically treated LC (1993-1997), the
      population with non-small cell lung cancer and complete resection was selected
      for the prognostic study of COPD. COPD is defined when the FEV1/FVC is <0.7
      (n=1370; 46%). Overall and conditional survivals (survival likelihood when alive
      at 2, 3 or 5 years after treatment) as well as the degree of severity (FEV1%
      percentiles) were calculated to establish prognosis. RESULTS: Although the
      overall survival is similar whether or not COPD is present (Log-rank: 0.34), the
      conditional survival analysis is different in every stage at 60 months (Log-rank:
      0.02) and different in stage pI at 24-36 months (Log-rank: 0.04). In LC (stage
      pI) with COPD, the presence of a worst pulmonary function (last FEV1% percentile
      vs first FEV1% percentile) is a bad prognostic factor (Log-rank: 0.002).
      CONCLUSIONS: The analysis of conditional survival at 24 months shows that COPD
      can be considered as a prognostic factor and that there is a clear relationship
      between the severity of the condition (FEV1%) and survival.

PMID- 15736304
TI  - Use of pedicled rectus abdominis muscle flap to protect against fistula formation
      after bladder neck closure.

PMID- 15736305
TI  - Apoptosis in cancer: archaeology, functional relevance and exploitation in novel
      treatment strategies.

PMID- 15736306
TI  - The effect of environmental pollution on the respiratory system of lignite
      miners: a diachronic study.
AB  - BACKGROUND: It is not known whether working in surface lignite mines can cause x
      ray lesions or disorders of respiratory function. OBJECTIVES: The aim of the
      study was to investigate the diachronic impact of environmental pollution on the
      respiratory system of lignite miners at mines in Eordea, Greece. METHODS: Cases
      of 199 workers (Group A) residing permanently in the Eordea valley and 151 (Group
      B) living outside the Eordea valley were studied during Phase I and then re
      examined after three years (Phase II). These cases were compared to those of 71
      office workers living in Eordea valley (Group C) and to 96 living in Grevena, a
      region without pollution (Group D). The study included the completion of the MRC
      questionnaire for the detection of respiratory diseases, pulmonary function
      tests, measurement of diffusion capacity, otorhinolaryngologic examination,
      rhinomanonetry as well as chest and paranasal cavity X-rays. RESULTS: Chronic
      bronchitis was reported by 26.8%, 24.8%, 17.9% and 10.6% respectively of the
      subjects of groups A, B, C and D according to the answers of the questionnaire
      (p<0.001). The spirometry and diffusion capacity findings presented no
      considerable differences either in the 4 groups or between phases I and II of the
      study. The main problems were detected in the upper airways. A very high
      prevalence of severe nasal obstruction (73%, 71.2%, 55.7% and 19.3% in Groups A,
      B, C and D respectively) was detected. Furthermore, a high percentage of atrophic
      rhinitis (14%) was detected both among workers (Groups A and B) and subjects
      living in the Eordea valley who participated as controls (Group C). From the X
      rays, hypertrophy of nasal turbinates-cartilage and polyposis was observed as
      follows: Group A: 53.9%, Group B: 48.1%, Group C: 46.5% and Group D: 20.3%
      (p<0.001). The findings related to the upper respiratory system may be due to
      excessive pollution by airborne particles (fly ash) pollution in the region and
      particularly to chromium, nickel, cobalt and lead found at high concentration
      levels in airborne dust. A marked association between the total air-flow in the
      nose and the mid-expiratory flow (p<0.01) was detected. CONCLUSIONS: We conclude
      that subjects working in lignite mines under conditions of excessive pollution by
      airborne contaminants have a high prevalence of atrophic rhinitis and, in
      addition to other standard examinations, should undergo rhinomanometry testing
      and X-ray imaging of the paranasal cavities.

PMID- 15736307
TI  - Partial gastrectomy for peptic ulcer: a review of 181 cases among British
      military personnel. 1957.

PMID- 15736308
TI  - [Esophagic varices].

PMID- 15736309
TI  - California adolescent's use of family planning services.

PMID- 15736310
TI  - Medical devices; medical device reporting. Direct final rule.
AB  - The Food and Drug Administration (FDA or we) is amending its regulation governing
      reporting of deaths, serious injuries, and certain malfunctions related to
      medical devices. We are revising the regulation into plain language to make the
      regulation easier to understand, and we are making technical corrections.
      Elsewhere in this issue of the Federal Register, we are publishing a companion
      proposed rule, under FDA's usual procedures for notice and comment, to provide a
      procedural framework to finalize the rule in the event we receive any significant
      adverse comment and withdraw the direct final rule.

PMID- 15736311
TI  - Pyruvate dehydrogenase and pyruvate dehydrogenase kinase expression in non small
      cell lung cancer and tumor-associated stroma.
AB  - Pyruvate dehydrogenase (PDH) catalyzes the conversion of pyruvate to acetyl
      coenzyme A, which enters into the Krebs cycle, providing adenosine triphosphate
      (ATP) to the cell. PDH activity is under the control of pyruvate dehydrogenase
      kinases (PDKs). Under hypoxic conditions, conversion of pyruvate to lactate
      occurs, a reaction catalyzed by lactate dehydrogenase 5 (LDH5). In cancer cells,
      however pyruvate is transformed to lactate occurs, regardless of the presence of
      oxygen (aerobic glycolysis/Warburg effect). Although, hypoxic intratumoral
      conditions account for HIF1alpha stabilization and induction of anaerobic
      metabolism, recent data suggest that high pyruvate concentrations also result in
      HIF1alpha stabilization independently of hypoxia. In the present
      immunohistochemical study, we provide evidence that the PDH/PDK pathway is
      repressed in 73% of non small cell lung carcinomas, which may be a key reason for
      HIF1alpha stabilization and "aerobic glycolysis." However, about half of PDH-HIF
      pathway, and patients harboring these tumors have an excellent postoperative
      outcome. A small subgroup of clinically aggressive tumors maintains a coherent
      PDH and HIF/LDH5 expression. In contrast to cancer cells, fibroblasts in the
      tumor supporting stroma exhibit an intense PDH but reduced PDK1 expression
      favoring maximum PDH activity. This means that stroma may use lactic acid
      produced by tumor cells, preventing the creation of an intolerable intratumoral
      acidic environment at the same time.

PMID- 15736312
TI  - [Diabetic retinopathy--staging and laser treatment].

PMID- 15736313
TI  - Association between pterostilbene and quercetin inhibits metastatic activity of
      B16 melanoma.
AB  - Inhibition of cancer growth by resveratrol (trans-3,5,4'-trihydroxystilbene;
      RESV), a phytoalexin present in many plant species, is limited by its low
      bioavailability. Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene; PTER) and
      quercetin (3,3',4',5,6-pentahydroxyflavone; QUER), two structurally related and
      naturally occurring small polyphenols, show longer half-life in vivo. In vitro
      growth of highly malignant B16 melanoma F10 cells (B16M-F10) is inhibited (56%)
      by short-time exposure (60 min/day) to PTER (40 microm) and QUER (20 microm)
      (approximate mean values of plasma concentrations measured within the first hour
      after intravenous administration of 20 mg/kg each polyphenol). Intravenous
      administration of PTER and QUER (20 mg/kg per day) to mice inhibits (73%)
      metastatic growth of B16M-F10 cell in the liver, a common site for metastasis
      development. The anti-metastatic mechanism involves: 1) a PTER-induced inhibition
      of vascular adhesion molecule 1 expression in the hepatic sinusoidal endothelium,
      which consequently decreases B16M-F10 cell adhesion to the endothelium through
      very late activation antigen 4; and 2) a QUER- and PTER-induced inhibition of Bcl
      2 expression in metastatic cells, which sensitizes them to vascular endothelium
      induced cytotoxicity. Our findings demonstrate that the association of PTER and
      QUER inhibits metastatic melanoma growth and extends host survival.

PMID- 15736314
TI  - Lamotrigine-induced rash--worth a rechallenge.
AB  - OBJECTIVES: The only serious adverse event associated with lamotrigine (LTG)
      treatment is a hypersensitivity reaction primarily presenting as a rash. Despite
      this concern, LTG is an antiepileptic drug (AED) with one of the most favorable
      efficacy/tolerability ratio compared with the new as well as the old AEDs. Thus,
      this study aimed to evaluate the results of rechallenge with LTG after the
      initial rash. MATERIAL AND METHODS: A total of 688 patients (350 as monotherapy,
      and 338 as add-on therapy) with either idiopathic generalized epilepsy or focal
      epilepsy were treated with LTG. The patients with LTG-induced rash were
      rechallenged to LTG. The dosage schedule was: 5 mg every day or every second day
      for 14 days, increased by 5 mg every 14th day to 25 mg a day. After achieving the
      daily dosage of 25 mg/day, the up-titration was completed following the current
      guidelines. RESULTS: A total of 52 patients developed a rash. The LTG-induced
      rash occurred in 6%, where 12 (1.8%) developed a rash shown to be coincidentally
      associated with the initiation of LTG therapy. In their cases LTG was continued
      with success without intermission. Nineteen (38%) of the initial cohort were
      rechallenged with LTG, with a success rate of 84%. CONCLUSION: This study is the
      first one to provide a successful recipe verified in time for the rechallenge
      with LTG after the initial drug-induced rash. Importantly, the concurrent use of
      valproate (VPA) was not found in this study to represent an additional risk
      factor for the occurrence of the rash during rechallenge with LTG. Our results
      agree with previous findings that women are more likely to develop the rash (P <
      0.009).

PMID- 15736315
TI  - When privacy fails: invoking a property paradigm to mandate the destruction of
      DNA samples.

PMID- 15736316
TI  - Interactive Health Communication Applications for people with chronic disease.

PMID- 15736317
TI  - Hedgehog signaling: from the Drosophila cuticle to anti-cancer drugs.
AB  - Hh signaling controls cell proliferation and differentiation in processes that
      range from insect segmentation and limb formation to vertebrate neural tube
      development and bone differentiation. Moreover, Hh signaling appears to regulate
      stem cell homeostasis in adult tissues, while persistent Hh pathway activity has
      pathological consequences in a number of cancers. Two recent meetings, a
      Karolinska Institute Nobel conference (August 22-24, 2004) and a joint EMBO and
      Juan March Institute workshop (October 25-27, 2004), provided the opportunity to
      take stock of the progress that has been made in understanding Hh signaling and
      also to remind us of the many questions that still remain unanswered.

PMID- 15736318
TI  - Application of GFP technique for cytoskeleton visualization onboard the
      International Space Station.
AB  - Cytoskeleton recently attracted wide attention of cell and molecular biologists
      due to its crucial role in gravity sensing and trunsduction. Most of cytoskeletal
      research is conducted by the means of immunohistochemical reactions, different
      modifications of which are beneficial for the ground-based experiments. But for
      the performance onboard the space vehicles, they represent quite complicated
      technique which requires time and special skills for astronauts. In addition,
      immunocytochemistry provides only static images of the cytoskeleton arrangement
      in fixed cells while its localization in living cells is needed for the better
      understanding of cytoskeletal function. In this connection, we propose a new
      approach for cytoskeletal visualization onboard the ISS, namely, application of
      green fluorescent protein (GFP) from Aequorea victoria, which has the unique
      properties as a marker for protein localization in vivo. The creation of
      chimerical protein-GFP gene constructs, obtaining the transformed plant cells
      possessed protein-GFP in their cytoskeletal composition will allow receiving a
      simple and efficient model for screening of the cytoskeleton functional status in
      microgravity.

PMID- 15736319
TI  - Plant molecular biology in the space station era: utilization of KSC fixation
      tubes with RNAlater.
AB  - Spaceflight experiments involving biological specimens face unique challenges
      with regard to the on orbit harvest and preservation of material for later ground
      based analyses. Preserving plant material for gene expression analyses requires
      that the tissue be prepared and stored in a manner that maintains the integrity
      of RNA. The liquid preservative RNAlater (Ambion) provides an effective
      alternative to conventional freezing strategies, which are limited or unavailable
      in current spaceflight experiment scenarios. The spaceflight use of RNAlater is
      enabled by the Kennedy space center fixation tube (KFT), hardware designed to
      provide the necessary containment of fixatives during the harvest and stowage of
      biological samples in space. Pairing RNAlater with the KFT system provides a safe
      and effective strategy for preserving plant material for subsequent molecular
      analyses, a strategy that has proven effective in several spaceflight
      experiments. Possible spaceflight scenarios for the use of RNAlater and KFTs are
      explored and discussed.

PMID- 15736320
TI  - Low-dose megavoltage cone-beam CT for radiation therapy.
AB  - PURPOSE: The objective of this work was to demonstrate the feasibility of
      acquiring low-exposure megavoltage cone-beam CT (MV CBCT) three-dimensional (3D)
      image data of sufficient quality to register the CBCT images to kilovoltage
      planning CT images for patient alignment and dose verification purposes. METHODS
      AND MATERIALS: A standard clinical 6-MV Primus linear accelerator, operating in
      arc therapy mode, and an amorphous-silicon (a-Si) flat-panel electronic portal
      imaging device (EPID) were employed. The dose-pulse rate of 6-MV Primus
      accelerator beam was windowed to expose an a-Si flat panel by using only 0.02 to
      0.08 monitor unit (MUs) per image. A triggered image-acquisition mode was
      designed to produce a high signal-to-noise ratio without pulsing artifacts.
      Several data sets were acquired for an anthropomorphic head phantom and frozen
      sheep and pig cadaver head, as well as for a head-and-neck cancer patient on
      intensity-modulated radiotherapy (IMRT). For each CBCT image, a set of 90 to 180
      projection images incremented by 1 degree to 2 degrees was acquired. The two
      dimensional (2D) projection images were then synthesized into a 3D image by use
      of cone-beam CT reconstruction. The resulting MV CBCT image set was used to
      visualize the 3D bony anatomy and some soft-tissue details. The 3D image
      registration with the kV planning CT was performed either automatically by
      application of a maximization of mutual information (MMI) algorithm or manually
      by aligning multiple 1D slices. RESULTS: Low-noise 3D MV CBCT images without
      pulsing artifacts were acquired with a total delivered dose that ranged from 5 to
      15 cGy. Acquisition times, including image readout, were on the order of 90
      seconds for 180 projection images taken through a continuous gantry rotation of
      180 degrees. The processing time of the data required an additional 90 seconds
      for the reconstruction of a 256(3) cube with 1.0-mm voxel size. Implanted gold
      markers (1 mm x 3 mm) were easily visible or all exposure levels without
      artifacts. In general, the presence of high Z materials such as tooth fillings or
      implanted markers did not result in visible streak artifacts. The registration of
      structures such as the spinal canal and the nasopharynx in the MV CBCT and kV CT
      data sets was possible with millimeter and degree accuracy as assessed by
      displacement simulations and subsequent visual evaluation. CONCLUSIONS: We
      believe that the quality of these images, along with the rapid acquisition and
      reconstruction times, demonstrates that MV CBCT performed by use of a standard
      linear accelerator equipped with a flat-panel imager can be applied clinically
      for patient alignment.

PMID- 15736322
TI  - Richard Dobson Kt MRCS FRS (1773-1847) and the inferior status of naval medicine
      in the early nineteenth century: end of the fleet physicians.
AB  - In the eighteenth and early nineteenth century assistant-surgeons in the Navy
      possessed an inferior status compared with their equivalents in the Army, despite
      protestations from the Physician of the Navy, Sir William Burnett FRS; lack of
      promotion was a major complaint. By abolishing the title physician in the Navy,
      Sir Richard Dobson, FRS, surgeon to Greenwich Hospital, did much to rectify this
      injustice. Instead of only two promotions in 26 years, 26 medical officers were,
      as a result of his exertions, advanced to the rank above that of Surgeon in two
      years.

PMID- 15736321
TI  - A Roman correspondence: George Ent and Cassiano dal Pozzo, 1637-55.
AB  - George Ent (FRS 1663), a distinguish physician, was in Rome in 1636, visited the
      notable collector Cassiano dal Pozzo and saw his Paper Museum. After he returned
      to London he carried on a correspondence with Cassiano in letters of more than
      ordinary interest. Cassiano had sent Ent specimens of fossil wood and a table
      made from fossil wood. They had come from the estates at Acquasparta belonging to
      Prince Federico Cesi, the founder of the Accademia dei Lincie. The specimens and
      the table were shown to early meetings of The Royal Society and had a significant
      part in the developing debate on the origin of fossils. The letters also record
      exchanges of books between London and Rome. Among medical matters there is news
      of William Harvey and his works.

PMID- 15736323
TI  - Needed: innovations in health.

PMID- 15736325
TI  - Medicare dentistry: the next logical step.

PMID- 15736324
TI  - Factors affecting implementation of the U.S. smallpox vaccination program, 2003.

PMID- 15736326
TI  - A model curriculum for public health bioterrorism education.
AB  - Beginning with the spring semester of 2001, a course designed to prepare future
      public health leaders for potential bioterrorism events has been offered by the
      University of Connecticut Graduate Program in Public Health. Entitled "The Public
      Health Response to Bioterrorism," this popular course was one of the few
      developed by academic programs in the United States prior to the attack of
      September 11, 2001. The course utilizes innovative teaching methods and
      presentations by distinguished guest speakers to educate public health personnel,
      public health and medical students, and physicians and nurses about the complex
      issues involved in the public health response to bioterrorism. The instructional
      methods and curriculum can serve as prototypes for similar efforts.

PMID- 15736327
TI  - Severe injury among Hispanic and non-Hispanic white children in Washington state.
AB  - OBJECTIVES: The authors' anecdotal experience at a regional Level I trauma center
      was that Hispanic children were overrepresented among burn patients, particularly
      among children with burns due to scalding from hot food. This study describes
      injury incidence and severity among Hispanic and non-Hispanic white infants,
      children, and adolescents with serious traumatic injuries in Washington State.
      METHODS: Data from the Washington State Trauma Registry for 1995-1997 were used
      to identify injured individuals aged < or = 19 years. Ratios of overall and
      mechanism-specific injury incidence rates for Hispanic children relative to non
      Hispanic white children were calculated using denominator estimates derived from
      U.S. Census Bureau population data. Hispanic children and non-Hispanic white
      children were also compared on several measures of severity of injury. RESULTS:
      In 1995-1997, serious traumatic injuries were reported to the Registry for 231
      Hispanic children aged < or = 19 years (rate: 54 per 100,000 person-years) and
      for 2,123 non-Hispanic white children (56 per 100,000 person-years), yielding an
      overall rate ratio (RR) of 1.0 (95% confidence interval [CI] 0.8, 1.1). Motor
      vehicle crashes and falls accounted for one-third to one-half of the injuries for
      each group. Infants, children, and adolescents identified as Hispanic had higher
      rates of injuries related to hot objects (i.e., burns) (RR=2.3; 95% CI 1.3, 4.1),
      guns (RR=2.2; 95% CI 1.5 to 3.3), and being cut or pierced (RR=3.5; 95% CI 2.2 to
      5.5). The Hispanic group had a lower injury rate for motor vehicle accidents
      (RR=0.7; 95% CI 0.5, 0.9). Mortality rates were similar (RR=1.1; 95% CI 0.7,
      1.7). The mean length of hospital stay was 5.5 days for the Hispanic group and
      8.8 days for the non-Hispanic white group (difference=3.3 days; 95% CI -0.7,
      7.4). CONCLUSIONS: The study found little difference between Hispanic and non
      Hispanic white infants, children, and adolescents in the burden of traumatic
      pediatric injury. However, burns, guns, drowning, and being pierced/cut appeared
      to be particularly important mechanisms of injury for Hispanic children. More
      specific investigations targeted toward these injury types are needed to identify
      the underlying preventable risk factors involved.

PMID- 15736328
TI  - Impact of a lead-safe training program on workers conducting renovation,
      painting, and maintenance activities.
AB  - OBJECTIVE: An important source of lead exposure is lead-based paint that is
      disturbed when unsafe work practices are used during renovation, remodeling, and
      maintenance activities. This study explores the success of a pilot lead-safe
      skills training program for home improvement contractors and their employees
      (including renovators, remodelers, and painters) and small property owners.
      METHODS: The study evaluates whether attendees at eight-hour lead-safe work
      practices training courses learned and retained information about lead exposure;
      developed and retained positive attitudes toward lead-safe work practices; and
      developed lasting, positive behavioral intentions to use lead-safe work practice
      skills and techniques. A questionnaire was administered immediately before,
      immediately following, and several months following the training program. Coded
      data from the questionnaires were analyzed using SPSS software. RESULTS:
      Respondents showed statistically significant changes from before to after the
      training program, and the changes were maintained over time. Knowledge improved,
      and attitudes and behavioral intentions changed in a favorable direction.
      CONCLUSION: These results suggest that lead-safe training can be successful and
      can create lasting changes in lead-safe knowledge, attitudes, and behaviors.

PMID- 15736329
TI  - Personal use of hair dyes and the risk of bladder cancer: results of a meta
      analysis.
AB  - OBJECTIVE: This study examined the methodology of observational studies that
      explored an association between personal use of hair dye products and the risk of
      bladder cancer. METHODS: Data were pooled from epidemiological studies using a
      general variance-based meta-analytic method that employed confidence intervals.
      The outcome of interest was a summary relative risk (RRs) reflecting the risk of
      bladder cancer development associated with use of hair dye products vs. non-use.
      Sensitivity analyses were performed to explain any observed statistical
      heterogeneity and to explore the influence of specific study characteristics of
      the summary estimate of effect. RESULTS: Initially combining homogenous data from
      six case-control and one cohort study yielded a non-significant RR of 1.01 (0.92,
      1.11), suggesting no association between hair dye use and bladder cancer
      development. Sensitivity analyses examining the influence of hair dye type,
      color, and study design on this suspected association showed that uncontrolled
      confounding and design limitations contributed to a spurious non-significant
      summary RR. The sensitivity analyses yielded statistically significant RRs
      ranging from 1.22 (1.11, 1.51) to 1.50 (1.30, 1.98), indicating that personal use
      of hair dye products increases bladder cancer risk by 22% to 50% vs. non-use.
      CONCLUSION: The available epidemiological data suggest an association between
      personal use of hair dye products and increased risk of bladder cancer.

PMID- 15736330
TI  - Socioeconomic factors and the risk of anencephaly in a Mexican population: a case
      control study.
AB  - OBJECTIVE: The study was designed to evaluate the association between
      socioeconomic level (as measured by maternal education, maternal occupation, and
      monthly family income) and anencephaly. METHODS: The authors conducted a case
      control study using data from the Epidemiological Surveillance System Register
      for Neural Tube Defects for three states of the Mexican Republic: Puebla,
      Guerrero and the State of Mexico. Mothers of 151 cases of infants born with
      anencephaly and mothers of 151 control infants born during the period March 2000
      to February 2001 were interviewed about their socioeconomic characteristics and
      other factors including reproductive history, use of prenatal care, use of
      tobacco and alcohol, fever during pregnancy, and folic acid supplementation.
      RESULTS: After adjustment for potential confounders, a risk gradient was seen
      with decreasing maternal education. Women with less than a primary school
      education (adjusted odds ratio [OR]=3.0; 95% confidence interval [CI] 1.2, 7.6)
      and women who had completed primary school but had not completed junior high
      school (adjusted OR=2.2; 95% CI 0.9, 5.7) had higher risks of giving birth to an
      infant with anencephaly, compared to women with a higher educational level. A
      monthly income < or = 1,000 pesos (approximately dollars 100 U.S.) was also
      associated with a higher risk of anencephaly (OR=2.5; 95% CI 1.2, 5.1). Women
      employed in industry or agriculture during the acute risk period (three months
      prior to conception to one month after conception) had a risk 6.5 times (95% CI
      1.4, 29.6) that of professional and business women. CONCLUSIONS: This study helps
      to identify groups that may be especially vulnerable to this type of congenital
      malformation so that primary and secondary preventive strategies can be targeted
      to these groups.

PMID- 15736331
TI  - Life expectancy without chronic morbidity: trends in gender and socioeconomic
      disparities.
AB  - OBJECTIVE: Life expectancy without chronic morbidity, or morbidity-free life
      expectancy (MFLE), was calculated to measure changes in population health status
      between 1989 and 2000 on the basis of gender and socioeconomic status. METHODS:
      Sullivan's method was used to calculate morbidity-free life expectancy.
      Prevalence rates for chronic morbidity were derived from the Netherlands
      Continuous Health Interview Survey. Four socioeconomic groups were distinguished
      on the basis of educational level. RESULTS: Between 1989 and 2000, total life
      expectancy increased for males and females and for all socioeconomic groups.
      Morbidity-free life expectancy decreased significantly for males (from 54.7 years
      to 53.9 years) and females (from 55.3 years to 51.0 years). The gap between males
      and females in MFLE has reversed, from 0.6 years in favor of females in 1989 to
      2.9 years in favor of males in 2000. The gap between the upper and lower classes
      seems to have narrowed (for males from 11 years to 8.5 years and for females from
      4.7 years to 4.0 years). CONCLUSIONS: The results indicate that morbidity-free
      life expectancy is falling for males and females and in all socioeconomic groups.
      Part of this decrease could be attributed to earlier diagnosis of chronic
      diseases. A widening gap in MFLE was observed between males and females in favor
      of males. The gap between the upper and lower socioeconomic groups seems to be
      narrowing.

PMID- 15736332
TI  - Influence of social factors on avoidable mortality: a hospital-based case-control
      study.
AB  - OBJECTIVE: The effect of socioeconomic factors on avoidable mortality at an
      individual level is not well known, since most studies showing this association
      are based on aggregate data. The purpose of this study was to determine
      socioeconomic differences between those patients who die of avoidable causes and
      those who do not die. METHODS: A matched case-control study was carried out
      regarding in-hospital avoidable mortality (Holland's medical care indicators)
      that occurred in a university hospital serving a Spanish-Mediterranean population
      during a 30-month period. RESULTS: We studied 82 cases of death from avoidable
      causes and 300 controls matched on medical care indicators and age. The variables
      that showed a statistically significant association with in-hospital avoidable
      mortality were number of diagnoses (the greater the number, the higher the risk),
      length of stay (patients staying seven or more days presented a lower risk), and
      education. Those patients with low and middle educational levels showed a greater
      risk of avoidable mortality (adjusted odds ratio=3.57 and 2.82, respectively)
      than those patients with higher levels of education. CONCLUSIONS: Consistent with
      the findings of studies based on aggregate data, our case-control analyses
      indicated that among several socioeconomic variables studied, educational level
      was significantly associated with the risk of in-hospital avoidable mortality,
      regardless of age and medical care indicators. Patients with low levels of
      education (<6 years of schooling) were at highest risk for in-hospital avoidable
      mortality, followed by those with middle levels of education (7-10 years of
      schooling).

PMID- 15736333
TI  - Residential injuries in U.S. children and adolescents.
AB  - OBJECTIVES: Injuries are the leading cause of death and disability for U.S.
      children, but little research exists on injury in the home environment. The
      purpose of this study was to estimate the rate and severity of and trends in
      unintentional residential injury for U.S. children <20 years for 1993-1999.
      METHODS: Data on emergency department (ED) visits were obtained from the National
      Hospital Ambulatory Medical Care Survey (NHAMCS). Rates and 95% confidence
      intervals (CIs) were calculated using SUDAAN. Chi-square analysis was used to
      test for differences among proportions. Time trends were analyzed using linear
      regression. RESULTS: Residential injuries accounted for an average of 4.01
      million (95% CI 3.50 million, 4.56 million) ED visits each year for U.S.
      children, representing 39% of unintentional injury ED visits. There were an
      average of 531,000 (95% CI 456,000, 606,000) visits with moderate-to-severe
      injuries, resulting in 73,680 (95% CI 59,715, 87,645) hospital admissions
      annually. The rate of residential injury visits (excluding unknown locations) was
      5.6 per 100 (95% CI 4.9 per 100, 6.4 per 100). The visit rates for children <5
      years of age were higher than those for children >9 years (p<0.0001). Males had a
      higher rate of visits than females (p=0.01). Falls were the leading mechanisms,
      resulting in 1.5 million ED visits per year (95% CI 1.3 million, 1.8 million).
      Residential injury rates decreased by 28% over time (p<0.02), from 6.3 per 100
      (95% CI 3.4, 9.2) in 1993 to 4.5 per 100 (95% CI 2.3, 6.7) in 1999. CONCLUSIONS:
      The predominant location of injury for U.S. children is the home, accounting for
      4.01 million ED visits and more than 70,000 hospitalizations each year. Efforts
      targeted to the home environment are needed to reduce morbidity and mortality
      from unintentional injury in U.S. children.

PMID- 15736335
TI  - Local public health system partnerships.
AB  - OBJECTIVES: Interorganizational collaboration aimed at community health
      improvement is an expectation of local public health systems. This study assessed
      the extent to which such collaboration occurred within one state (Wisconsin),
      described the characteristics of existing partnerships, and identified factors
      associated with partnership effectiveness. METHODS: In Stage 1, local health
      department (LHD) directors in Wisconsin were surveyed (93% response rate). In
      Stage 2, LHDs completed self-administered mailed surveys for each partnership
      identified in Stage 1 (85% response rate). Two-level hierarchical logit
      regression methods were used to model relationships between partnership and LHD
      variables and partnership outcomes. Data from 924 partnerships associated with 74
      LHDs were included in the analysis. RESULTS: Partnerships most frequently
      addressed tobacco prevention and control, maternal and child health, emergency
      planning, community assessment and planning, and immunizations. Partnering was
      most frequent with other government agencies, hospitals, medical practices or
      clinics, community-based organizations, and schools. Partnership effectiveness
      was predicted by having a budget, having more partners contributing financially,
      having a broader array of organizations involved, and having been in existence
      for a longer period of time. A government mandate to start the partnership was
      inversely related to successful outcomes. Characteristics of LHDs did not predict
      partnership effectiveness. CONCLUSIONS: Financial support, having a broader array
      of partners, and allowing sufficient time for partnerships to succeed contribute
      to partnership effectiveness. Further study-using objective outcome measures-is
      needed to examine the effects of organizational and community characteristics on
      the effectiveness of local public health system partnerships.

PMID- 15736334
TI  - Depression and hip fracture risk: the NHANES I epidemiologic follow-up study.
AB  - OBJECTIVE: Since hip fracture is the most devastating consequence of osteoporosis
      from a public health standpoint, addressing whether depression is predictive of
      fracture risk is important. The purpose of this study is to determine whether
      individuals with high depressive symptomatology are more likely to suffer an
      osteoporotic hip fracture than subjects with intermediate or low depressive
      symptomatology. METHODS: Data from the first National Health and Nutrition
      Examination Survey (NHANES I) were obtained from a nationally representative
      sample of noninstitutionalized civilians. A cohort aged 25 through 74 at baseline
      (1971-1975) was observed through 1992. Subjects were followed-up for a maximum of
      22 years. Included in the analyses were 6,195 white and black subjects. Ninety
      five percent of the original cohort completed the study. Hospital records and
      death certificates were used to identify a total of 122 hip fracture cases.
      RESULTS: In an unadjusted Cox proportional hazards regression model for all
      individuals, depression was predictive of hip fracture (hazard ratio [HR]=1.90;
      95% confidence interval [CI]=1.13, 3.21; p=0.016). In a multivariate proportional
      hazards model controlling for (1) age at baseline, (2) gender, (3) race, (4) body
      mass index, (5) smoking status, (6) alcohol consumption, and (7) physical
      activity level, high depressive symptomatology remained predictive of hip
      fracture (HR=1.70; 95% CI=0.99, 2.91; p=0.055). CONCLUSIONS: This study gives
      evidence of a prospective association between depression and hip fracture.
      Additional studies are needed to verify these findings and to elucidate the
      pathways for the effects of depression on hip fracture incidence.

PMID- 15736336
TI  - Effect of release from prison and re-incarceration on the viral loads of HIV
      infected individuals.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of release from
      prison and subsequent re-incarceration on the viral loads of HIV-infected
      individuals receiving highly active antiretroviral therapy (HAART). METHODS:
      Fifteen re-incarcerated HIV-infected prisoners on HAART were identified from a
      retrospective cohort of HIV-infected prison inmates released from January 1,
      1997, to August 31, 1999. The re-incarcerated prisoners were matched (1:2) to 30
      HIV-infected incarcerated prisoners on HAART who remained incarcerated during the
      re-incarcerated participants' release time period. The outcomes measured were
      plasma HIV RNA levels, CD4+ lymphocyte counts, percentage of re-incarcerated and
      incarcerated participants with plasma HIV RNA levels <400 copies/mL, and the
      median change in plasma HIV RNA levels of the re-incarcerated and incarcerated
      participants at the end of the study. RESULTS: At the beginning of the study,
      8/15 re-incarcerated participants had plasma HIV RNA levels <400 copies/mL,
      compared with 15/30 incarcerated participants. At the end of the study, only
      three of those eight re-incarcerated participants had plasma HIV RNA levels <400
      copies/mL, compared with 14/15 incarcerated participants (p=0.0086). The median
      change in plasma HIV RNA levels of the re-incarcerated participants was 1.29
      log10 copies/mL (interquartile range 0.04 to 1.70), compared with -0.03 log10
      copies/mL (interquartile range -0.65 to 0.09) in the incarcerated participants
      (p=0.0183). CONCLUSIONS: Release from prison was associated with a deleterious
      effect on virological and immunological outcomes. These data suggest that
      comprehensive discharge planning efforts are required to make certain that HIV
      infected inmates receive access to quality care following incarceration.

PMID- 15736338
TI  - The case of Laguna Honda.

PMID- 15736337
TI  - Date of first positive HIV test: reliability of information collected for
      HIV/AIDS surveillance in the United States.
AB  - OBJECTIVES: This study examined the reliability of the first positive HIV test
      date reported in the U.S. HIV/AIDS Reporting System (HARS). This date is
      essential to determine case counts for resource allocation for HIV treatment and
      prevention efforts. METHODS: The dates of first positive HIV tests reported by
      individuals with HIV in an interview survey conducted in 16 states (n=16,394,
      interviewed 1995-2002) were compared with the dates of HIV diagnosis reported to
      HARS. The percentage of agreement for the year of diagnosis and the weighed kappa
      (k) with 95% confidence intervals (CIs) was calculated. RESULTS: Self-reported
      year of diagnosis agreed with the year of diagnosis in HARS for 56% of date pairs
      (k=0.69; 95% CI 0.68, 0.70); 30% reported an earlier diagnosis year. Agreement
      differed by sex, age, race, exposure, and reason or place of testing (p<.01).
      Lower agreement was found when the self-reported diagnostic test was anonymous
      (k=0.57; 95% CI 0.52, 0.62) compared with confidential tests (k=0.66; 95% CI
      0.64, 0.68). Lower agreement was also found for cases first reported with AIDS
      (k=0.58; 95% CI 0.55, 0.62) compared with cases first reported with HIV not AIDS
      (k=0.71; 95% CI 0.70, 0.73) as well as for participants interviewed three years
      or more after their HARS diagnosis date (k=0.55; 95% CI 0.52, 0.57) compared with
      those interviewed within one year (k=0.62; 95% CI 0.61, 0.63). More than 20% of
      participants in almost all groups, however, reported earlier diagnosis years than
      those recorded in HARS. CONCLUSION: As many as 30% of HIV diagnoses may have
      occurred earlier than recorded in HARS. Additional studies need to determine
      mechanisms to adequately capture diagnosis dates in HARS.

PMID- 15736339
TI  - The Loma Linda experience.

PMID- 15736340
TI  - A new EVP chosen.

PMID- 15736341
TI  - The characterization of ozone exposures in rural West Virginia and Virginia.
AB  - Ozone (O3) is suspected of being the most significant air pollutant affecting
      vegetation in the United States. Ozone concentrations measured at Bearden Knob
      and Parsons, located in a remote forested region of northcentral West Virginia,
      were characterized and compared with exposures experienced at other sites in the
      region. From 1988 to 1992, 1988 was one of the highest O3 exposure years in the
      region, while 1992 was the lowest. At almost all sites in 1992, few hourly
      average concentrations were > or = 0.10 ppm, while in 1988 several sites had more
      than 100 hourly average concentrations > or = 0.10 ppm. These instances occurred
      at both high- and low-elevation sites. In 1992, the high-elevation Bearden Knob
      site experienced a flat-type diurnal pattern, while the nearby low-elevation
      Parsons site experienced a changing diurnal pattern, indicative of scavenging.
      Using several indices, O3 exposures at Parsons were less than those at Bearden
      Knob. Evaluation of hourly averaged data for all sites in the region from 1988 to
      1992 showed that Horton Station experienced the highest W126 O3 exposures. Horton
      Station is a high-elevation site in the mountains of southwestern Virginia.
      Square-wave exposures have been used under artificial conditions in vegetation
      experiments. If square-wave exposures are observed under ambient conditions, then
      the vegetation data collected under artificial conditions may be relevant for
      predictive purposes. Square-wave exposures were characterized for two high
      elevation sites. In 1992, Horton Station experienced 25 episodes for which the
      hourly average concentrations remained near 0.05 ppm for eight hours or longer;
      there were 18 episodes for which the hourly average concentrations remained near
      0.06 ppm, and three episodes for which the concentrations remained near 0.07 ppm.
      Bearden Knob experienced 31 episodes of eight hours or longer for hourly average
      concentrations near 0.05 ppm, 13 episodes at or near 0.06 ppm, and three episodes
      at or near 0.07 ppm. Until experiments are performed to determine the relative
      importance of hourly average concentrations above 0.03 ppm for assessing
      vegetation effects, using single-parameter exposure indices to predict effects
      may produce inconsistent results.

PMID- 15736342
TI  - Remote sensing data and a potential model of vehicle exhaust emissions.
AB  - In June 1991, General Motors Research and Development Center (GMR&D) participated
      in a remote sensing study conducted by the California Air Resources Board and the
      U.S. Environmental Protection Agency. During this study, the GMR&D remote sensor
      was used to measure the carbon monoxide (CO) and hydrocarbon (HC) emissions from
      approximately 15,000 vehicles. The vehicle type (passenger car, light-duty truck,
      or medium/heavy-duty truck), manufacturer, and model year were identified for
      each vehicle by acquiring registration data from the state of California.
      Analyses were performed separately for each vehicle type and for passenger cars
      by separate model years. The data indicate that the passenger cars with the
      highest 10% of CO emissions generated approximately 58% of the total CO from all
      cars. Similarly, the 10% highest HC-emitting cars generated 65% of the total HC
      from cars. It was found that for each model year of vehicle, the distribution of
      emission concentrations followed a logarithmic relationship. The logarithmic
      functions that describe these relationships can be used to estimate the fraction
      of vehicles that emitted at or above any given concentration of CO or HC.
      However, these logarithmic functions only describe measured distributions for
      vehicles emitting more than 1% CO and 0.015% HC.

PMID- 15736343
TI  - Landfill gas effects on groundwater samples at a municipal solid waste facility.
AB  - A study was performed to determine the source of low concentrations of volatile
      organic compounds (VOCs) detected in groundwater samples at a solid waste
      management facility. The affected wells were identified as hydraulically
      upgradient of an old unlined facility, but downgradient of a new clay-lined
      landfill. These monitoring wells are close to both sites. Subsurface landfill gas
      migration was identified after a low permeability cap was installed on the older
      site. Subsurface gas pressure was monitored to identify horizontal landfill gas
      migration. Monitoring well headspace gases were evaluated to identify depressed
      oxygen concentrations and methane because of landfill gas migration into the
      well. Monitoring well headspace gas VOC concentrations were compared to
      groundwater VOC concentrations to determine the direction of phase transfer. A
      ratio above 1.0 of the observed well headspace gas concentration of a VOC to the
      concentration that would be in equilibrium with the groundwater concentration
      indicates gas-to-water phase transfer within the well. For the major gas-phase
      and aqueous-phase VOC, cis-1,2-dichloroethene, gas-to-water phase transfer is
      clearly indicated from the data for two of the four wells. Fifteen other VOCs
      were detected in monitoring well headspace gases but not in groundwater samples
      from the four wells studied. Only one compound in one well was detected in the
      groundwater sample but not in the headspace gases, and only one compound in one
      well was detected in both matrices at concentrations that suggested water-to-gas
      phase transfer. This study suggests that if landfill gas is suspected as the
      source of detected VOCs, monitoring well construction and stratigraphy are
      important considerations when attempting to differentiate between groundwater
      contamination by landfill gas and contamination from other sources.

PMID- 15736344
TI  - An exposure system for the calibration of passive samplers to volatile organic
      compounds at low (ppbv) concentrations.
AB  - A recycling exposure system, which has characteristics of dynamic and static
      systems, has been designed and constructed for calibrating passive sampling
      tubes. This system is very easy to set up and maintain. Organic vapors inside the
      system are generated by syringe injection, and homogeneous vapors are circulated
      by a metal-bellows pump. The concentrations of light hydrocarbons (e.g.,
      isoprene) may decrease slightly after circulating for longer than 10 hours;
      however, this system is very stable for C5-C8 hydrocarbons for at least eight
      hours. The system has been used successfully to calibrate Perkin-Elmer diffusion
      tubes packed with Chromosorb 106 for collecting benzene vapor at low exposure
      doses (< 70 ppmv x min). The entire system can be easily and effectively cleaned
      by circulating through a U-tube packed with activated carbon.

PMID- 15736345
TI  - Pollution balance: a new methodology for minimizing waste production in
      manufacturing processes.
AB  - A new methodolgy based on a generic pollution balance equation, has been
      developed for minimizing waste production in manufacturing processes. A
      "pollution index," defined as the mass of waste produced per unit mass of a
      product, has been introduced to provide a quantitative measure of waste
      generation in a process. A waste reduction algorithm also has been developed from
      the pollution balance equation. This paper explains this methodology and
      demonstrates the applicability of the method by a case study.

PMID- 15736346
TI  - How does waste-to-energy "stack" up?
AB  - To put waste-to-energy (WTE) in perspective, it is important to see how it
      measures up environmentally to other power generation utility sources. This paper
      compares actual WTE facility emissions with those from fossil fuel combustion
      utility sources. This comparison is made on an electricity production basis, such
      as a pound of pollutant per megawatt-hour of net electricity generated, for each
      ower generation source.

PMID- 15736347
TI  - N2O emissions at solid waste disposal sites in Osaka City.
AB  - Nitrous oxide (N2O) is a trace gas contributing to stratospheric ozone depletion
      and global warming. Although a large quantity of information exists about N2O
      emissions from various ecosystems, this study was initiated to demonstrate the
      features of N2O emissions from sea-based waste disposal sites in Osaka City in
      relation to CH4 emissions. Average N2O emissions at an active landfill (S-Site)
      were several times higher than those at a closed landfill (N-Site). Average CH4
      emissions were also much greater at the S-Site. Regarding the nature of N2O
      emissions, remarkable emissions often were observed with aerobic waste layers at
      the N-Site, suggesting almost inversely related N2O emissions with CH4 production
      at the N-Site. However, at the S-Site a few exceptionally high N2O emissions were
      noted in cases of high CH4 emissions.

PMID- 15736348
TI  - Biofiltration control of hydrogen sulfide. 2. Kinetics, biofilter performance,
      and maintenance.
AB  - The kinetics of H2S oxidation in a biofilter were evaluated and the reaction
      rates determined to be first-order at low concentrations (< 200 ppm), zero-order
      at high concentrations (> 400 ppm), and fractional-order in the intermediate
      concentration range for H2S in the inlet waste gas. The overall performance of
      the biofilter system and changes in compost properties were investigated for 200
      days of operation. The compost biofilter showed good buffering capacities to
      variations in gas flow rate and pollutant (H2S) loading impacts. Hydrogen sulfide
      removal efficiencies exceeding 99.9% were consistently observed. System
      acidification and sulfate accumulation were identified as inhibitors of required
      biological activity. Routine washing of the compost effectively mitigated these
      deficiencies. System upset was determined to be caused by compost dry-out or
      system overloading. Methods were developed to provide for recovery of
      contaminated filter material.

PMID- 15736349
TI  - Occurrence of Burkholderia cepacia in the hospital environment.
AB  - AIM: To determine the prevalence of Burkholderia cepacia from the environment in
      a regional adult cystic fibrosis (CF) care centre. METHODS: Two hundred and
      eighty-five environmental samples were taken from inpatient and outpatient
      environments within the CF centre. Following a non-selective enrichment step,
      broths were plated onto a selective medium and B. cepacia isolates were confirmed
      by phenotypic tests and also genotypically by species specific 16S rRNA PCR.
      RESULTS: B. cepacia was not detected from commonly shared items of equipment,
      staff hands, staff uniforms or toilets. In addition, the organism was not
      detected in toilet bowls, even in the B. cepacia unit. With regard to positive
      environments for B. cepacia, 4/10 (40%) of the outside surfaces and inner rims of
      patients' plastic disposable sputum collection containers and 4/17 (23.5%) of air
      from patients' rooms, following physiotherapy, were positive. CONCLUSIONS: All
      positive samples originated in the B. cepacia segregation area of the inpatient
      wards and B. cepacia was not detected in the non-cepacia area of the CF centre.
      Consequently, these two positive sites should therefore be treated as high risk,
      where organisms may be potentially transmitted from environment to patient. As
      there is now evidence to suggest differences in the virulence and hence clinical
      outcome of certain of the genomovars of this organism, this study may be
      important in highlighting the areas that patients who are B. cepacia positive
      should avoid, to minimise the risk of transmission and acquisition of this
      organism within the CF cepacia population. These results indicate that effective
      infection control procedures are required in patients' rooms following
      physiotherapy, for prevention of B. cepacia transmission and to avoid the
      transmission of different genomovar types within CF patients, who are already
      colonised with this pathogen.

PMID- 15736350
TI  - Measures of self-reported morbidity according to age, gender and general medical
      services eligibility in the national survey of lifestyles, attitudes and
      nutrition.
AB  - BACKGROUND: The survey of lifestyles, attitudes and nutrition (SLAN) is a
      national representative sample of 6,539 adults. AIMS: To report on both global
      and disease specific measures of self-reported morbidity according to age, gender
      and medical card status. METHODS: Reported rates of morbidity are given for
      angina, heart attack, stroke, raised blood pressure, cholesterol, diabetes
      mellitus and for other general conditions as well as difficulty with hearing and
      glasses/contact lens use. Stratified chi-squared analysis of categorical
      variables was conducted and logistic age adjusted regression model with general
      medical services (GMS) eligibility as the dependent variable. RESULTS: All
      conditions were more prevalent after the age of 45 years and showed a continuing
      age gradient. There were highly statistically significant inverse morbidity
      patterns according to GMS status among both men and women. Only reported raised
      cholesterol level was higher among the more affluent (13.5% males and 13.3%
      females over 45 years without a medical card, compared with 7.3% and 9.5% card
      holders respectively), one suggested explanation is the lack of access to means
      tested screening. CONCLUSIONS: There is considerable morbidity in the Irish
      population, particularly among GMS card holders.

PMID- 15736351
TI  - Late presentation of developmental dysplasia of the hip.
AB  - BACKGROUND: A neonatal screening programme for developmental dysplasia of the hip
      (DDH) is ongoing in Cork. Despite early screening, infants continue to present at
      later ages with DDH. The impact of late diagnosis is significant. Established DDH
      causes significant morbidity and may have major medicolegal implications. AIM: To
      identify the reasons for the late presentation of DDH in the presence of a
      screening programme. METHODS: In a retrospective study all cases of late DDH
      presenting from 1988 to 2000 were identified using inpatient database. RESULTS:
      Forty-nine cases of DDH were diagnosed. The mean age of diagnosis was 14.8 months
      (range 6-47). Multiple risk factors were identified in four patients only. More
      than one risk factor was identified in 10 patients. CONCLUSION: Despite
      screening, children continue to present with late DDH. In this study, only 14
      patients had multiple risk factors and only four patients had more than two risk
      factors, highlighting the low incidence of suspicion in this patient group.

PMID- 15736352
TI  - Cyclizine and droperidol have comparable efficacy and side effects during patient
      controlled analgesia.
AB  - BACKGROUND: Post-operative nausea and vomiting (PONV) is common, especially
      following gynaecological surgery. Patient-controlled analgesia (PCA) is
      frequently complicated by nausea. We assessed PONV, pain and sedation in patients
      receiving cyclizine or droperidol during PCA following abdominal hysterectomy in
      a double-blind trial. METHODS: Thirty women were randomised to receive either
      cyclizine 0.7 mg/kg or droperidol 0.04 mg/kg during surgery followed by PCA
      containing morphine sulphate with cyclizine 2 mg or droperidol 0.05 mg per
      demand. Blinded observers scored levels of nausea, sedation, anxiety and pain.
      RESULTS: Pain scores, PCA usage and supplemental antiemetic requirements were
      comparable. Nausea and sedation scores were similar in both groups. Two patients
      in each group developed refractory PONV. Pre-operative anxiety scores were
      similar and decreased comparably over time. Patients developing refractory emetic
      sequelae had a higher incidence of previous PONV. Previous PONV also predicted
      lower PCA medication intake despite similar demand rates, suggesting increased
      usage during lock-out periods. CONCLUSION: Prophylactic cyclizine and droperidol
      have similar efficacy during PCA. Neither is associated with perioperative
      anxiety. A minority of patients have refractory PONV during PCA. Previous PONV
      may predict less efficient PCA usage.

PMID- 15736353
TI  - The prevalence of coeliac disease among female subjects having bone densitometry.
AB  - BACKGROUND: Osteoporosis frequently complicates coeliac disease but most studies
      focus on symptomatic patients at the time of diagnosis. Screening tests have
      revealed that many individuals with coeliac disease have mild, atypical, or
      absent symptoms. AIM: To evaluate the relationship between coeliac disease and
      osteopenia or osteoporosis in female subjects attending for bone densitometry.
      METHODS: We studied 371 female subjects attending for bone densitometry, without
      secondary causes of osteoporosis and included those with normal and with reduced
      bone mineral density. Mineral density was measured by dual energy X-ray
      absorptiometry. Screening for coeliac disease was by measurement of anti
      endomysial antibody by indirect immunofluorescence. RESULTS: Two of 115 (1.7%)
      female subjects with normal bone density and five of 256 (1.9%) female subjects
      with sub-normal bone density were positive for endomysial antibody. Five subjects
      who underwent small bowel biopsy had histological changes suggestive of coeliac
      disease. CONCLUSIONS: In females referred for bone densitometry, endomysial
      antibody positivity was not more prevalent among those with reduced bone mineral
      density. Examining only patients with clinically detected coeliac disease may
      overestimate the frequency of complications. This study does not support
      population screening for coeliac disease in an area with a high frequency of the
      condition.

PMID- 15736354
TI  - Ease of access is a principal factor in the frequency of paracetamol overdose.
AB  - BACKGROUND: In Ireland, 30% of non-fatal overdoses involve paracetamol. AIMS: To
      determine how and where patients obtained paracetamol, to assess awareness of
      toxicity and examine the relationship between dose and suicidal intent. METHODS:
      A prospective study of patients admitted following a paracetamol overdose
      recording their reasons for using paracetamol, their knowledge of its toxicity
      and their suicidal intent scale (SIS). RESULTS: Of 100 patients, 66% obtained
      paracetamol in non-pharmacy outlets, 82% cited ease of availability as the
      reason, 55% were aware of its toxicity, 31% of liver damage and 68% did not read
      the warning on packets. The mean number of tablets taken was 51.3 for males and
      37.2 for females (p < 0.01). Males presented later than females for medical
      attention (12.5 versus seven hours [p < 0.02]) and more males than females took
      alcohol (p < 0.03). The mean SIS score was 14.71 for males and 12.38 for females.
      There was a significant correlation between the SIS and the amount of paracetamol
      consumed (r = 0.28; p < 0.01). CONCLUSION: The majority obtained paracetamol in
      local shops or at home. Knowledge of toxicity and the need for early antidote was
      poor. There was a significant relationship between suicidal intent and number of
      tablets consumed. Limiting availability could reduce number of overdoses.

PMID- 15736356
TI  - Outcome of calcaneal fractures treated operatively and non-operatively. the
      effect of litigation on outcomes.
AB  - BACKGROUND: The optimum management of calcaneal fractures is controversial. These
      injuries are frequently associated with compensation litigation, which effects
      the outcome. AIMS: To assess the outcome of operatively and conservatively
      managed intra-articular calcaneal fractures and to examine the effect of
      compensation litigation on outcome. METHODS: This was a retrospective study of
      calcaneal fractures from a single regional trauma unit, with management decided
      by the admitting consultant surgeon's preference. Fifty-four patients (33
      operative, 21 conservative) with an average follow-up of 40 months (range 14-78
      months) were reviewed. Sixteen patients (30%) were pursuing a compensation case
      resulting from the injury. RESULTS: Despite similar fractures, medical co
      morbidity and trauma energy, significantly worse outcome scores were seen in
      litigants (p < 0.0001). Footwear fitting problems were greater in litigants. Time
      off work was more than twice that of non-litigants (14.5 vs 6 months, p < 0.01).
      Results were similar between the operative and non-operative groups in terms of
      functional score, footwear problems and time off work. CONCLUSIONS: Litigation
      was the major determinant of outcome following calcaneal fracture repair;
      highlighting the unreliability of subjective evaluation in determining outcome in
      the face of litigation. No subset of patients appeared to significantly benefit
      from internal fixation of their fracture.

PMID- 15736357
TI  - High dose chemotherapy and stem cell support for poor risk and recurrent
      nonseminomatous germ cell cancer: initial experience with sequential therapy.
AB  - BACKGROUND: Approximately 20% of patients with germ cell tumours do not respond
      fully to standard therapy, or relapse after treatment. The prognosis of these
      patients is poor with conventional chemotherapy. Preliminary data suggest that
      they may have a higher durable response rate with high dose chemotherapy and
      peripheral blood stem cell support. AIMS: To treat a group of testicular cancer
      patients, either with relapsed disease or with poor prognostic features
      initially, with high dose chemotherapy and stem cell support, and evaluate their
      outcome. METHODS: Five patients with testicular cancer were treated with high
      dose chemotherapy and stem cell support. Of these, four underwent this treatment
      as salvage therapy and one patient with poor prognostic features was treated as
      primary treatment. RESULTS: At an average follow-up of 18 months, four patients
      remain free of disease while one patient has developed relapse. CONCLUSION: This
      report provides further support for high dose chemotherapy in this setting
      although randomised, controlled trials are essential to clarify its use.

PMID- 15736355
TI  - Transcatheter occlusion of the patent ductus arteriosus: a comparison of two
      devices.
AB  - BACKGROUND: Transcatheter occlusion of the arterial duct is a safe and effective
      alternative to surgical closure. The Rashkind umbrella occluder and the Cook coil
      are two established devices, although the former is no longer manufactured. AIMS:
      To assess any difference in outcomes between the use of the Cook detachable coil
      and the Rashkind double umbrella in patent ductus arteriosus (PDA) occlusion.
      METHODS: A retrospective study of 77 patients in whom PDA occlusion was attempted
      using the Cook detachable PDA coil from March 1996 to March 2000. A comparison
      was carried out with patients in whom occlusion was attempted using the Rashkind
      double umbrella between 1989 and 1996. RESULTS: The rate of immediate complete
      occlusion was 24% compared with 29.9% for the Rashkind device. The figure for
      complete occlusion after 24 hours with the PDA coil was 63% compared with 61.5%
      in the Rashkind group (p > 0.1). The overall closure rate in the coil group was
      72% versus 74.6% for umbrellas. CONCLUSION: The outcome in terms of complete duct
      closure using the Cook coil is comparable with figures obtained using the
      Rashkind umbrella. Both devices have a good safety profile in the short and
      medium-terms.

PMID- 15736359
TI  - Conway Review Lecture 2001. Atheroma and the mechanics of blood flow in arteries.

PMID- 15736360
TI  - A beautiful mind.

PMID- 15736358
TI  - Hyperglycaemia: the relation to dyslipidaemia and atherosclerosis.

PMID- 15736361
TI  - Condylomata acuminata of the urinary bladder: a case report.

PMID- 15736362
TI  - Bilateral posterior shoulder dislocation associated with fracture.

PMID- 15736363
TI  - Fractures around implants used for hip fracture fixation.

PMID- 15736364
TI  - Conservative management of epiploic appendagitis based on CT scan findings.

PMID- 15736365
TI  - Enterocutaneous fistula due to polypropylene mesh migration.

PMID- 15736366
TI  - Systemic effects of intravesical BCG treatment.

PMID- 15736367
TI  - The largest reported papillary renal cell carcinoma.

PMID- 15736368
TI  - Hypocalcemia-associated coronary vasospasm.

PMID- 15736369
TI  - Work-related asthma in teachers in Connecticut: association with chronic water
      damage and fungal growth in schools.
AB  - PURPOSE: To review a series of 55 teachers from schools in Connecticut who
      presented consecutively to our clinic, and to summarize our clinical experience
      with work-related disease in this population, which could lead to a more formal
      study. METHODS: Retrospective chart review; data were abstracted concerning
      clinical and environmental factors and entered into a statistical spreadsheet
      program (JMP for Windows). RESULTS: Of the 55 educators, 22 were diagnosed with
      upper respiratory syndromes (rhinitis or sinusitis), three with bronchitis, and
      23 with asthma. Of the 23 with asthma, 20 presented with active or symptomatic
      asthma, and seven of these were incident cases of occupational asthma. In
      addition, four cases (7%) of granulomatous lung disease (two hypersensitivity
      pneumonitis and two sarcoidosis) were diagnosed. Finally, three patients (5%)
      received only nonrespiratory diagnoses (panic disorder, sicca syndrome, and
      vertigo). In 33 work-places, the exposures of concern were predominantly related
      to ongoing "dampness" or visible mold growth. The remaining 22 work-places were
      "dry." Symptoms varied according to the work-place environment, with more
      patients from water damaged (vs dry) work-places having upper respiratory
      symptoms (76% vs 45%) and asthma (45% vs 23%). All seven patients with incident
      asthma and all four patients with interstitial lung disease worked in schools
      with documented water incursion. CONCLUSIONS: Work-place exposures in water
      damaged school buildings are risk factors for development of work-related lower
      respiratory disease in schoolteachers and staff. Identification of such high-risk
      environments can be done by a simple but thorough qualitative evaluation during a
      walk-through inspection, and it should not require air sampling or surface
      sampling protocols for microbial contaminants.

PMID- 15736370
TI  - Cost-effectiveness of statin monotherapy and combination therapy with ezetimibe.

PMID- 15736371
TI  - Medical errors and quality of care in Connecticut hospitals. Grappling with the
      implications of the IOM reports.

PMID- 15736372
TI  - A defendant's tale.

PMID- 15736373
TI  - Honoring Horace Wells.

PMID- 15736374
TI  - Consumer-Driven Health Plans: implications for doctors.

PMID- 15736375
TI  - Re: Inglorious "old glory".

PMID- 15736376
TI  - [Extent of lymphadenectomy in lung resection for carcinoma].
AB  - Dissemination of the bronchogenic carcinoma into the lung and mediastinal
      lymphonodes is considered one of the basic prognostic factors. Correct evaluation
      of the lymphonodes involvement remains the principal pre-requisite for the choice
      of the most appropriate procedure and makes a forecast of a particular patient's
      perspective possible. The preoperative diagnostics of malignant lymphadenopathy
      is based on a CT examination. Once enlarged lymphonodes are detected, invasive
      exploration is indicated--either via mediastinoscopy, eventually via
      thoracoscopy. The final picture of the extent of the tumor dissemination via
      lymphatics is provided by the final histopathological examination of the
      lymphonodes removed during the surgical procedure. The minimal extent of
      lymphadenectomy is still being discussed. Some clinics do not conduct it at all.
      On the other hand, there are some clinics, where the en-bloc mediastinal
      lymphonodes dissection remains a common procedure during all lung carcinoma
      surgical procedures. On the group of 226 patients operated between 1996-1999, the
      authors assess surgical aspects and complications of the lymphadenectomic
      procedure within the radical lung resection for the non-spinocellular lung
      carcinoma. In the subgroup of 73 patients with a confirmed malignancy of the lung
      lymphonodes, the authors have found no statistical difference in the five-year
      survival rate which would be connected to lymphadenectomy. Mediastinal
      lymphadenectomy, with respect to its sound diagnostic and prognostic benefits,
      remains a necessary part of any curative resection. It proved to improve local
      control of the tumor, however, it has no clear influence on the survival rate. In
      small peripheral tumors (T1, T2), its extent may be restricted to systematic
      sampling of the interlobium, lung hilus and medistinum lymphonodes. On the other
      hand, in case of advanced tumors after the induction therapy, no other than en
      block resection procedures are suitable or even possible.

PMID- 15736377
TI  - [Minilaparotomy as an access route to vascular reconstruction procedures in the
      aortoiliac region].
AB  - Following the example of general surgical procedures, also vascular surgery
      gradually minimizes the size of its surgical entrances. Miniinvasive surgical
      procedures significantly reduce postoperative complaints and shorten the patients
      recovery rates. Minilaparotomy, either a hand-assisted or a laparoscopy-assisted
      procedure, a procedure conducted fully via laparoscopy or thoracoscopy and a
      robot-assisted procedure, all of the above are contemporary options for
      miniinvasive procedures in the vascular surgery. The authors introduce their
      initial experience with the use of minilaparotomy in the aortoiliac region. From
      November 2002 to April 2004, 29 procedures were performed for the abdominal
      aortic aneurysm repair or for aortoiliac occlusive disease. In 15 cases the
      abdominal aortic aneurysm was managed and in 14 cases the aortoiliac occlusive
      disease was managed.

PMID- 15736378
TI  - [Laparoscopic vascular reconstructions--initial experience].
AB  - Laparoscopic techniques, which have been found useful in the general surgical
      procedures, have influenced the vascular surgical procedures with a certain
      delay. The main reason for the delay were technical difficulties of the vascular
      anastomosis, which resulted in a reluctant acceptance of the laparoscopic
      procedures by vascular surgeons. However, with respect to clear benefits of the
      miniinvasive procedures, including reduction of the postoperative pain, faster
      recovery rates and reduction of the total treatment costs, the laparoscopic
      procedures are finally being applied in the vascular surgery as well. The authors
      introduce operative results and outcome of ten laparoscopic vascular procedures
      for aortoiliac occlusive disease, which were conducted from September 2003 to
      April 2004. In five cases, iliofemoral bypasses were conducted, fourtimes
      unilateral aortofemoral bypasses (AF) and once an aortobifemoral bypass (ABF).
      All the IF and AF reconstructions were conducted via laparoscopy and the ABF
      reconstruction was conducted as laparoscopy-assisted.

PMID- 15736379
TI  - [Esophageal stents].
AB  - The method of oesophageal stents application using a surgical procedure via
      gastrotomy for otherwise surgically unmanageable malignant stenoses of the
      oesophagus and the gastric cardia, has been used for several decades. Once the
      self-expandible endoprostheses, applied under either the endoscopical or
      radiological (RTG) control, or both, and following a change in the oesophageal
      malignities treatment strategy, the spectrum of indication groups of the
      patients, who would undergo the stent implantation, have enlarged. Recently,
      thank to the endoscopically removable endoprostheses, the authors broaden the
      spectrum of use to benign findings of the oesophageus and the gastric cardia
      (strictures, perforations, insuficiency of anastomoses), as well. In their work,
      the authors present a group of patients who have had the oesophageal stent, using
      the endoscopic method, implanted at the Surgical Clinic of the Faculty Hospital
      in Plzen since 1992.

PMID- 15736380
TI  - [A laparoscopic management of an iatrogenic lesion of the colon during a
      colonoscopy].
AB  - The colon injury during a colonoscopy is a rare, however a serious complication,
      requiring, mostly, a surgical management. Only few patients may undergo a
      conservative treatment. The authors discuss the problem of the iatrogenic colon
      perforation during the colonoscopy and they assess a benefit of the miniinvasive
      surgery in the diagnostics and treatment algorithm. The main benefit is seen in
      the reduction of the surgical intervention risks, in the surgical trauma
      minimalisation, in more favourable postoperative status and in the possibility of
      the definitive injury management.

PMID- 15736381
TI  - [Therapeutic approach for treatment of postoperative ileus].
AB  - The postoperative motility disorder of the gastrointestinal tract (POI) is a
      transient, however a frequent reaction of the gastrointestinal tract to
      intraabdominal procedures. The cause of the onset of the POI is multifactoral
      and, therefore, the treatment must also cover all known pathophysiological
      causes. The management of the POI includes the following basic measures:
      employment of the minimally invasive surgical techniques, prophylactic
      administration of the prokinetics, early postoperative mobilisation of the
      patient and early enteral nutrition.

PMID- 15736382
TI  - [Isolated rupture of the gall bladder following a blunt abdominal injury].
AB  - The study presents a rare isolated rupture of the gall bladder following a blunt
      abdominal injury. The diagnostics was complicated by inaccurate anamnestic data,
      because the patient was injured in the drunken state and could not remember it.
      The clinical picture was extremely nonspecific. Repetitive ultrasound
      examinations aided a correct clinical decision making and an adequate management.
      A possibility of the gall bladder perforation following blunt injuries of the
      abdomen must be considered mainly in younger patients with nonspecific abdominal
      pains. The risk increases after abuse of alcohol or after prolonged starvation.

PMID- 15736383
TI  - [Neurolyses of the brachial plexus and peripheral nerves of the extremities].
AB  - AIM: This study presents the results of the brachial plexus and the peripheral
      extremities nerves neurolyses conducted in our clinic for 18 years from 1985 to
      2003. SUBJECTS AND METHODOLOGY: 92 patients were treated surgically using
      neurolyses. Out of this number, 10 of them concerned brachial plexi, 49 nerves of
      the upper extremities and 33 nerves of the lower extremities. Out of the total
      patient number, 67 were males and 25 females, aged 30 years on average. The
      average time gap between the injury and the surgical procedure was 6.9 months. An
      extremely long time gap (over 12 months) was recorded in 5 cases. The operations
      were conducted in patients who suffered from a complete or persisting
      neurological deficits. In 92 patients, external neurolysis was conducted, out of
      them in 7 cases also internal neurolysis was conducted. Cases which required
      resection of the fascicles and reconstruction using autotransplants, as well as
      cases which had already undergone reconstruction procedures, have not been
      included in this study. The results analysis has been conducted with respect to
      the time gap between the surgical procedure and the injury, to the patient's age,
      to the type of the injured nerve and to the peroperatively detected degree of
      fibrotic changes. RESULTS: The best results were observed in patients under 20
      years of age, in cases of early treatment, in distal injuries and in neurolyses
      of the tibial and radial nerves. CONCLUSION: When indicated, the early surgical
      treatment is the main factor determining the results of the surgical procedures.

PMID- 15736384
TI  - [Recent patho-biochemical view of ischemia-reperfusion injury].
AB  - Ischemia-reperfusion injury (IRI) in patients with limb ischaemia remains still a
      topical problem and it is a subject of research. Some degree of tissue injury is
      expressed in each patient, regardless of type of ischaemia (acute or chronic).
      The difference is stated in extent of injury and in clinical relevance. In our
      article we provide current theoretical view of IRI and possibilities to influence
      it.

PMID- 15736385
TI  - [The influence of chloroquine on some biochemical and hematological parameters in
      patients with critical limb ischemia].
AB  - CLI represents a major medical and social problem. The incidence is increasing
      and currently it was estimated 500-1000 per 1 million inhabitants. We carried out
      a clinical study (2000-2004) concerning monitoring of some hematological and
      biochemical markers during reperfusion in patients with CLI. The subject of our
      interest included possibilities to influence PMNL elastase by medical means and
      neutrophil-lymphocyte ratio which is considered a reliable and simple parameter
      to assess severity of clinical conditions.

PMID- 15736386
TI  - [Infections of vascular reconstructions in the aortofemoral region].
AB  - Infections of vascular reconstructions in the aortofemoral region are among the
      most feared of conditions in the vascular surgery, having a very poor prognosis.
      The perioperative mortality reaches over 50% and the extremity loss up to 75%.
      The authors point out inaccuracies in diagnostics and definitions of the vascular
      reconstructions infections. On four cases of the vascular reconstructions
      infections in the aortofemoral region which have been managed in the Surgical
      Clinic in Plzen in last two years, they demonstrate severity of the above
      conditions.

PMID- 15736387
TI  - [A vascular surgeon and intervention].
AB  - Multisegmental affections of the arteries of the lower extremities are frequently
      connected with two- or more-step revascularisation--vascular reconstructions and
      radiological interventions. Recently, due to improvements in radiological
      visualizing equipment and due to the miniinvasive methods trend, the interest of
      vascular surgeons in conducting single-step complex revascularisations (joining
      classical vascular procedures and interventions) has been on increase. The aim of
      this study was to present the scope of use, the literature data and our
      experience with introduction of these methods.

PMID- 15736388
TI  - [Surgical therapy of the ductal carcinoma in situ].
AB  - AIM: Rates of the newly-detected DCIS reach up to 20% in developed countries.
      There is no unified therapeutic scheme to deal with the disorder. The aim of this
      work is to assess the author's own therapeutic results. METHODOLOGY: From 1999
      until 2003, 11 female patients suffering from the DCIS were treated and 2 DCIS
      female patients were treated using microinvasion. The diagnosis was established
      5x by the core-cut and 8x by the surgical excision. RESULTS: The size of the
      tumors varied from 0.5 cm to 6.0 cm. Conservative procedures were performed 11
      times, a simple mastectomy once and a mastectomy with reconstruction once, as
      well. The sentinel lymphonodes were examined in all cases and once the
      examination was accompanied by the axilla dissection. The number of the sentinel
      lymphonodes was 29. All of the lymphonodes were negative. Seven female patients
      were given a complementary therapy. All female patients have had no local relapse
      in the breast and have had no signs of the disease process since. The average
      follow-up time is 13.5 months. CONCLUSION: The conservative procedures
      sufficiently provide treatment of early forms of the DCIS of the breast. The
      sentinel lymphonode biopsy is a patient- kind method, giving exact information on
      the status of the axillary lymphonodes and it is considered a suitable part of
      the DCIS therapy.

PMID- 15736389
TI  - [The surgeon as a university educator and scientist].

PMID- 15736390
TI  - [Reflection on contemporary options for the esophageal carcinoma treatment].
AB  - Our opinions on contemporary strategies for the oesophageal carcinoma treatment,
      based on our oesophageal resections results, conducted in last five years, are
      presented in this study. RESULTS: From 2000 to 2004/VIII, 86 resections of the
      oesophagus were conducted. None of the patients exited. 18 serious complications
      were recorded (21%). METHODOLOGY: Surgical treatment procedures of the
      oesophageal carcinoma have been significantly influenced by miniinvasive
      techniques. Also our team employed laparoscopy as well as thoracoscopy. This
      technique appears to have a positive effect on both the immediate postoperative
      results and the long-term results, as it makes any increase in the procedure's
      radicality possible, mainly at the second level. The authors discuss the
      procedure's radicality degree as well as its limitations CONCLUSION: Although the
      oesophageal carcinoma treatment results have definitely improved, especially when
      lethality rates and morbidity rates are concerned, the long-term results have
      remained unsatisfactory, though the surgical treatment is combined with the
      oncological treatment (neoadjuvant, adjuvant). The radicality of the procedure
      itself is unlikely to have much influence on the above long-term results.

PMID- 15736391
TI  - [Aanalysis of the brachial plexus traumatic lesions reconstructive procedures
      unfavourable results].
AB  - AIM: The aim of this study is to analyze unfavourable results of nerve transfers
      to the musculocutaneous nerve, using upper intercostal nerves. METHODOLOGY: The
      trial group included 7 patients with traction injuries of the brachial plexus,
      who were treated surgically, using intercostal nerves as nerve transfers. The
      follow-up period was at least 3 years. The analysis of the motor function
      recovery depended on the respective patient's age and the operation time.
      RESULTS: In not a single case a functional recovery of the musculocutaneous nerve
      was achieved. CONCLUSION: The time gap between the injury and the operation, the
      level and the extent of the nerve injury and the type of the reconstructive
      procedure, all the above are the main prognostic factors for the functional
      recovery of the paralyzed muscles, resulting from its traction injury.

PMID- 15736392
TI  - [Anatomic variations of the radial artery. Their relationship to radial artery
      harvest for coronary artery bypass grafting. Review].
AB  - Radial artery increasingly is being used for coronary bypass grafting. Anatomic
      variantions of radial artery are rare but their clinical knowledge is important
      for surgeon performing radial artery harvest. We review the most often anatomic
      variations of radial artery on forearm and their influence to clinical practice.

PMID- 15736393
TI  - [Breast reconstructions using thoracodorsal flaps according to Holmstrom--a
      fourteen-year experience].
AB  - Breast reconstructions after completed mastectomies using fascio-cutaneous flaps
      in combination with silicone prostheses implantations, are considered routine
      breast reconstruction procedures. The authors present their fourteen-year
      experience with the breast reconstructions using the thoracodorsal flaps with the
      silicone prostheses.

PMID- 15736395
TI  - [Necrotizing enterocolitis in extremely immature newborns. The surgical treatment
      potential].
AB  - AIM: The aim of this study is to assess a contemporary treatment potential for
      necrotizing enterocolitis in newborns with birth weights under 1000 g.
      METHODOLOGY AND SUBJECTS: This is a retrospective study of clinical and
      pathological data in a group of 19 newborns with birth weights under 1000 g
      treated for necrotizing colitis (NEC) by the authors' team from 1999 to 2003.
      Only newborns with the second and third grade NEC according to Bell were included
      in the trial group. RESULTS: The trial group included 19 newborns born in the
      26th gestation week, on average (ranging from 23- to 31) with a mean birth weight
      of 711 grams (the range between 460-980 g). Their NEC appeared on the 18th
      postnatal day, on average (the range between 6-59). Ten newborns were operated in
      the acute stage of their NEC, nine were treated conservatively. Five infants
      operated in the acute stage had separational ileostomy conducted, four had a T
      drain introduced and one had an abdominal drain introduced. In the conservatively
      managed group, three infants were consequently operated for intestinal strictures
      following their NEC, two recovered during the conservative treatment and four
      exited due to a fast progress of their NEC without surgery. The total mortality
      rate of the trial group was 42% (8 infants exited). CONCLUSION: The NEC treatment
      in the extremely immature newborns with birth weigts under 1000 g requires
      complex cooperation of a neonatologist and a paediatric surgeon. The necrotic
      intestine resections followed by stomic procedures remain standard procedures in
      unstable newborns with a localised form of the disease.

PMID- 15736394
TI  - [Preoperative biliary drainage in the pancreatic head carcinoma].
AB  - Hemipancreatoduodenectomy has remained afflicted with high postoperative
      morbidity rates. Preoperative icterus is considered a significant risk factor.
      Therefore, a preoperative biliary drainage has been considered a standard
      preoperative procedure. This study aims to assess the preoperative drainage of
      the biliary tract significance with respect to the postoperative complications
      rates. SUBJECTS AND METHODOLOGY: This retrospective study includes 304 patients
      after completed hemipancreatoduodenectomies, who were operated in the 1st
      Surgical Clinic of the 1st Medical Faculty of the Charles University and the
      General Faculty Hospital in Prague between January 1990 and December 2002. In
      this trial group, 144 patients had underwent preoperative drainage of the biliary
      ducts and 160 patients underwent surgical procedures without the preoperative
      drainage. RESULTS: In the trial group, no significant difference in the gender
      rates, the history of the risk factors, the surgical procedure duration, the
      perioperative blood loss and the disease stage was detected. The patient trial
      group with the preoperative drainage of the biliary ducts completed was
      statistically significantly older (p = 0.05), had higher serum bilirubin levels
      recorded (118, respectively 81, p = 0.01), had more complications recorded
      postoperatively (42.4%, respectively 25%; p = 0.05), and more infectious
      complications (29%, respectively 13%; p = 0.05) when compared with the trial
      group without the preoperative drainage completed. Upon comparison of the both
      groups, we have not detected any statistically significant differences regarding
      the time interval between the diagnosis and the surgical procedure, the
      hospitalization duration or the mortality rates. CONCLUSION: The operated who had
      had the internal drainage of the biliary ducts conduted preoperatively, suffered
      from more complications in total as well as from more infectious complications,
      compared with the patients without the drainage. On the other hand, the patients
      who had had the preoperative drainage completed were older and had had higher
      preoperative bilirubin levels. With respect to the above results we strongly
      advise the patients with the pancreatic head carcinoma to early consult a
      hepatobiliary surgeon. As far as the examination algorithm is concerned, we
      strongly recommend using not only the spiral CT, but also non-invasive methods of
      examination (the MRI and the MRI cholangiography).

PMID- 15736396
TI  - [Laparoscopic fundoplication. Indications and preoperative examinations].
AB  - AIM: The aim of this study is to assess success rates and risks of laparoscopic
      antireflux procedures, based on 2000 completed surgical procedures. METHODOLOGY:
      We compared our experience with literature data. We concenterated on indications,
      preoperative examinations range and the procedure's technique itself. RESULTS: It
      is advisable to indicate patients with already advanced disorders and hiatal
      hernias, after the procedure's principles and possible side-effects have been
      explained to them. It is also advisable to carefully indicate young, polymorbid
      and depressive patients. The higher the expertise of the operating team, the less
      contraindications for the procedure occur. The preoperative examination should be
      sufficient enough to exclude any diagnostic errors. Fibroscopy, preferably
      conducted repeatedly, is necessary. PH-metry and oesophageal manometry may aid to
      exclude incorrect indications and, on the contrary, may confirm the diagnosis in
      cases of non- typical clinical manifestations. Radiography may depict hernias,
      stenoses, the oesophagus length, its relation to the diaphragm. CONCLUSION: The
      result of any antireflux surgical procedure depends on its correct indication, on
      a complete exhaustion of the patient's history data, on a rational assessment of
      the preoperative examination results. Education of the patient is necessary.

PMID- 15736397
TI  - [Laparoscopic fundoplication. The surgical technique].
AB  - The antireflux plastic procedures have a broad spectrum of its variations. The
      best results have been recorded with circular procedures with a good mobilization
      of the distal oesophagus and cardia, with or without interruption of the vasa
      brevia. The hiatal suture is always conducted. The rim (cuff) should be short, 25
      30 mm, applied loosely around the mobilized abdominal oesophagus with an inserted
      gastric tube (at least 12 mm). The surgeon must consider any peroperative
      fingdings. All his movements, location and application of each stitch would
      decide about the procedure's successful outcome.

PMID- 15736398
TI  - [Biologic characteristics of invasive bladder cancer: is there a difference
      between primary and progressive tumours?].
AB  - OBJECTIVE: In most muscle-invasive bladder cancer muscle invasion is present at
      the time of first diagnosis (primary tumours), in the rest of the patients muscle
      invasion is caused by progression of superficial tumours (progressive tumours).
      The aim of study is to determine whether a difference in natural history is
      between primary and progressive tumours. MATERIAL AND METHODS: In 1997-2001 we
      treated 278 patients with bladder cancer, 167 (60.1%) patients had superficial
      tumours and 111 patients had invasive tumours. At the time of diagnosis muscle
      invasion of the bladder was present in 90 (81.1%) patients, in 21 (18.9%)
      invasion was formed by progression of superficial tumours. The retrospective
      study evaluated and compared characteristics of patients (incl. survival) and
      tumours. Statistical significance was calculated by the chi2 test. RESULTS: A
      mean age of patients with primary tumours was 65.2 +/- 10.5 years, compared with
      mean age of 61.7 +/- 12.6 years of patients with progressive tumours. Gender-
      male:female ratio was 3.1:1 in primary tumours, as opposed to 4.2:1 in
      progressive. Progression of superficial tumours was noted on average within 35.4
      months (range of 7-115). Within one year died 46 out of 90 (51.1%) patients with
      primary tumours and 11 out of 21 (52.4%) patients with progressive tumours. Three
      years survived 14 out of 61 (23%) patients with primary tumours and two out of 13
      (15.4%) with progressive tumours. CONCLUSIONS: Prognosis of patients with
      progressive tumours is worse than prognosis of patients with primary invasive
      tumours. It is vital to detect superficial tumours in their pre-invasive stage,
      when they can be treated successfully.

PMID- 15736399
TI  - Visualizing portal vein metastatic trafficking to the liver with green
      fluorescent protein-expressing tumor cells.
AB  - Cell migration or trafficking is an integral aspect of cancer metastasis and is a
      target for development of novel antimetastatic therapy. Tumor cell trafficking
      has been a poorly understood phenomenon due to the inability to visualize the
      process. In this study, we visualized the trafficking of metastatic cells
      targeting the liver via the portal vein using green fluorescent protein (GFP)
      expressing cancer cells. Within 72 h after transplantation of tumor cells, on the
      ascending colon in nude mice, metastasis was visualized ex vivo on a single-cell
      basis around the portal vein by GFP imaging. At this early time-point, a few
      cells were visualized trafficking to the liver via the portal vein. By post
      implantation day-5, the caudate lobe of the liver was involved with trafficking
      metastatic cells. Metastasis around the portal vein increased more rapidly than
      those in other areas of the liver. By day-7 post-implantation, the right lateral
      lobe of the liver was involved with trafficking metastatic cells. By days-9 and 
      11, metastasis increased rapidly around the portal vein and then spread to other
      areas of the liver. These experiments demonstrate the critical role of the portal
      vein in metastasis to the liver.

PMID- 15736400
TI  - Prognostic value of the expression of Smad6 and Smad7, as inhibitory Smads of the
      TGF-beta superfamily, in esophageal squamous cell carcinoma.
AB  - BACKGROUND: The transforming growth factor beta (TGF-beta) superfamily regulates
      cell growth in various cells. Previous studies have shown that altered expression
      of TGF-beta receptors, Smad2 and Smad4, as mediators of TGF-beta superfamily
      signaling, contributes to tumor progression in esophageal squamous cell carcinoma
      (SCC). The expression of Smad6 and Smad7 as negative regulators was examined, to
      investigate the further effects of TGF-B superfamily signaling. MATERIALS AND
      METHODS: Immunohistochemical staining with anti-Smad6 and anti-Smad7 polyclonal
      antibodies was performed on surgical specimens obtained from 115 patients with
      esophageal SCC. RESULTS: The expression of Smad6 and Smad7 was inversely
      correlated with depth of invasion in the early stages (p = 0.0003 and p = 0.0173,
      respectively). Moreover, there was a significant correlation between the
      expression of Smad6 and Smad7, and poor survival rate (p = 0.0078 and p = 0.0207,
      respectively). CONCLUSION: Smad6 and Smad7 expression affects the progression of
      early lesions of esophageal SCC and indicates a poor prognosis.

PMID- 15736401
TI  - Expression of chemokine receptor CXCR6 in human colorectal adenocarcinomas.
AB  - Infiltration of inflammatory cells into colorectal adenocarcinomas is considered
      of importance for tumour progression. Tumour-associated macrophages and T cells
      are predominant components of the chemokine-guided filtrate of most colorectal
      tumours. CXCR6 is a chemokine receptor expressed by Th1, Tc, NKT cells and smooth
      muscle cells. To determine whether CXCR6 is expressed in human colorectal cancer
      and corresponding normal tissue, we analysed CXCR6 protein expression in 32
      surgical specimens. Immunohistochemistry revealed CXCR6 protein predominantly
      localised in normal epithelial cells and some scattered stromal cells. No or weak
      expression was found in cancerous tissue. Western blot analysis showed, in 41% of
      the cases, a notable suppression of CXCR6 protein (p < 0.05) in cancerous tissue
      compared with non-cancerous tissue. Up-regulation was found in 9% of the cases.
      CXCR6 protein expression, in 25% of the cases, showed no difference between
      tumour and adjacent normal tissue. Furthermore, 25% of the cases revealed
      undetectable levels of CXCR6 protein in tumour as well as corresponding normal
      tissue. The results may reflect one of the immunological features of normal and
      cancerous colorectal tissue and studies on regulation of CXCR6 are necessary in
      order to determine its role in colorectal carcinogenesis.

PMID- 15736402
TI  - Targeted gene expression using a 1.1 kilobase promoter fragment of the tumour
      associated antigen EpCAM.
AB  - The epithelial cell adhesion molecule EpCAM is over- or de novo expressed during
      carcinogenesis. EpCAM expression correlates with increased proliferation and
      dedifferentiation. Recently, we reported the cloning of a 1.1 kilobase fragment
      upstream of the epcam gene and demonstrated its specific transcriptional
      activity. Here, we analyzed the potential of this fragment for targeted gene
      expression. The fragment was used to regulate the expression of the green
      fluorescent protein (GFP) and HSV-1 thymidine kinase (HSV-TK), as a model
      therapeutic gene. Transfection of the pEpProm-control or pEpProm-GFP plasmids
      resulted in the expression of functional GFP and HSV-TK proteins specifically in
      EpCAM-positive cells. Expression levels of both proteins correlated with the
      amount of EpCAM. Additionally, the targeted expression of HSV1-TK transferred a
      marked sensitivity to ganciclovir treatment in EpCAM-positive HEK293-EBNA1 and
      SkBr3 carcinoma cells. The EpCAM promoter fragment is, thus, a novel tool to
      allow for the transcription of therapeutic genes, specifically, in EpCAM-positive
      carcinomas.

PMID- 15736403
TI  - Antibiotics directly induce apoptosis in B cell lymphoma cells derived from
      BALB/c mice.
AB  - BACKGROUND: The effects of bacterial eradication therapy cannot be fully
      explained simply by elimination of the target bacteria, if one considers the
      effects of eradication therapy in H. pylori-negative cases of low-grade
      malignancy MALTomas of the rectum. The present study was undertaken to examine
      the possibility and mechanism of direct induction of apoptosis of the tumor cells
      by the antibiotics used for bacterial eradication therapy. MATERIALS AND METHODS:
      A B cell lymphoma cell line (300-19) derived from BALB/c mice was co-cultured
      with amoxicillin or clarithromycin, and amoxicillin and clarithromycin at
      concentrations equal to or 1/10 x MIC of either drug. Cells co-cultured with
      1/100 x MIC of the standard anti-tumor agents, adriamycin, vincristine and
      cyclophosphamide, served as positive controls. Cells cultured without any
      antibiotic or anti-tumor agent served as controls. In each group, the following
      analyses were performed: (i) the time-course of changes in the cellular
      morphology, (ii) the time-course of occurrence of DNA fragmentation, (iii) the
      appearance of apoptotic changes as evaluated by trypan blue staining, (iv) Bcl-2
      expression as examined by immunoblotting; and (v) the expression of TNFR1, Fas,
      FasL and caspase-3, -8 and -9, as evaluated by immunoblotting. RESULTS: Cells
      treated with amoxicillin and clarithromycin showed the formation of apoptotic
      bodies, and degeneration and detachment of the cells in a dose-dependent manner.
      DNA fragmentation was induced in these cells to a degree similar to that seen in
      cells treated with the anti-tumor agents. Trypan blue staining also demonstrated
      apoptosis of the cells and loss of cell viability. Bcl-2 expression was seen only
      in the control group and FasL was never seen, while the expression of TNFR1, Fas
      and caspase-3, -8 and -9 was seen in the amoxicillin-treated group,
      clarithromycin-treated group, amoxicillin and clarithromycin-treated group and
      the positive control group. CONCLUSION: Antibiotics used for the eradication of
      H. pylori can also directly induce apoptosis in mouse B cell lymphoma cells, an
      action which involves the TNF system.

PMID- 15736404
TI  - Plasminogen activator inhibitor-1 is a downstream mediator of the PGP9.5-related
      oncogenic pathway in esophageal squamous cell carcinoma.
AB  - BACKGROUND & MATERIALS AND METHODS: Recently, it has been proved that PGP9.5 is
      an oncogene candidate for squamous cell carcinomas. To examine the PGP9.5-related
      oncogenic pathway, we tested for global patterns of gene expression in cancer
      cells following PGP9.5 gene introduction using an oligonucleotide microarray
      approach. RESULTS: Plasminogen activator inhibitor-1 (PAI-1) was identified as an
      overexpressed gene in a PGP9.5-expressed esophageal squamous cancer cell line. To
      confirm the data obtained, we performed Northern analysis using a PGP9.5 or a PAI
      1 cDNA probe and found that PAI-1 mRNA was induced by PGP9.5 expression in NUEC1
      cells. We further examined endogenous PGP9.5 and PAI-1 expression in 6 esophageal
      cancer cell lines. One cell line (NUEC2) with PGP9.5 expression exhibited PAI-1
      expression, suggesting the possibility that PGP9.5 might induce PAI-1 directly or
      indirectly. CONCLUSION: These results suggested that PAI-1 might be a novel
      downstream mediator of PGP9.5 in esophageal squamous cell carcinomas.

PMID- 15736405
TI  - Growth hormone receptor antagonist administration inhibits growth of human
      colorectal carcinoma in nude mice.
AB  - Increasing evidence has accumulated in support of the hypothesis that growth
      hormone (GH) and insulin-like growth factors (IGFs) play a role in
      carcinogenesis. In order to test this hypothesis, female nude mice were
      xenografted with two different human colorectal cancer cell lines (COLO 205 and
      HT-29) and randomized to receive placebo or a GH receptor antagonist (GHRA)
      (B2036-PEG) every second day for 16 days. The tumour volume was measured in each
      animal throughout the study and by the end of the experiment the tumour weights
      were recorded. After 16 days of therapy in nude mice with the COLO 205 colorectal
      cancer, GHRA treatment caused a 39% reduction in tumour volume (p < 0.02) and a
      44% reduction in tumour weight (p < 0.01). GHRA treatment equally reduced
      circulating IGF-I and IGFBP-3 levels, while apoptosis was increased in the
      treatment group. Expression of IGF-I, IGF-II and the corresponding receptors in
      COLO 205 tumours was also decreased by the treatment. GHRA had no effect on the
      growth of the HT-29 colorectal cancer despite pronounced reduction in serum IGF
      I. The present study thereby demonstrates a central role for the GH/IGF system in
      the pathogenesis of some colorectal cancers and suggests that specific GHR
      blockade may present a new concept in the treatment of colorectal cancer.

PMID- 15736406
TI  - Characterization of osteosarcoma cell lines MG-63, Saos-2 and U-2 OS in
      comparison to human osteoblasts.
AB  - BACKGROUND: Osteosarcomas are malignant bone tumors consisting of cells with
      abnormal cellular functions. Although osteosarcoma-derived cells are commonly
      used for osteoblastic models, the molecular composition of the osteosarcoma
      extracellular matrix (ECM) is not well characterized. MATERIALS AND METHODS: We
      compared three osteosarcoma cell lines (MG-63, Saos-2 and U-2 OS) with normal
      human osteoblasts by immunocytochemistry. Cellular characteristics were assessed
      by morphometric analysis and proliferation kinetics. RESULTS: All investigated
      osteosarcoma cell lines exhibited very heterogeneous labelling profiles and each
      differed significantly from that of normal osteoblasts. Saos-2 cells revealed the
      most mature osteoblastic labelling profile while U-2 OS cells were negative for
      most of the investigated osteoblastic markers. CONCLUSION: We conclude that each
      osteosarcoma cell line exhibits a characteristic labelling profile and thus
      produces a differently composed extracellular matrix. This can be used in
      attempts to better characterize osteosarcoma, a as well as for their diagnosis.

PMID- 15736407
TI  - Non-genomic cell growth inhibition by progesterone. cell cycle retardation and
      induction of cell death.
AB  - BACKGROUND: Non-genomic mechanisms have been proposed to play a role in
      progesterone-dependent cell growth inhibition. MATERIALS AND METHODS: The human
      cell line C-4I, derived from a squamous carcinoma of the uterine cervix, was
      progesterone receptor-negative. The culture medium contained 10% (v/v) fetal calf
      serum and the cells, growing in monolayer, were exposed to various progesterone
      concentrations. Flow cytometry and morphometry were employed to assess the
      effects. RESULTS: Progesterone caused a concentration-dependent growth inhibition
      with an IC50 value of 2.06 +/- 0.46 microM (mean value +/- SEM, n = 4). At 320
      microM no viable and attached cells were left. Two mechanisms appeared to be
      responsible for the effect. Firstly, the cells accumulated in the G1/G0-phase
      indicating a cell cycle-specific arrest. Secondly, progesterone induced cell
      death with apoptosis and necrosis. Morphometric analysis showed that progesterone
      caused a marked reduction in the nuclear size, compatible with apoptosis.
      CONCLUSION: The present results show that progesterone exerts non-genomic
      effect(s) by reducing the input of and accelerating the exit of cells from the C
      4I cell population.

PMID- 15736408
TI  - The preventive effect of green tea on the gap junction intercellular
      communication in renal epithelial cells treated with a renal carcinogen.
AB  - OBJECTIVE: Clinical studies imply that (-)-epigallocatechin-3-gallate (EGCG), a
      main ingredient of green tea catechins, has a chemopreventive action against
      cancers and suppresses the proliferation of cancer cells. However, there is no
      report about its chemopreventive effect for renal cancer. We previously
      determined that renal carcinogens suppressed the gap junction intercellular
      communication (GJIC) of renal epithelial cells. In this study, we investigated
      the effect of EGCG on the GJIC of renal epithelial cells treated with a renal
      carcinogen. MATERIALS AND METHODS: Mardin-Darby canine kidney (MDCK) cells were
      used to determine the protective effects of EGCG on dimethylnitrosamine-induced
      alteration of GJIC and connexin 43 (Cx 43). The maximum concentration of EGCG was
      determined by the lactate dehydrogenase assay method. The scrape-loading dye
      transfer method was used to assess the expression and cellular localization of Cx
      43. The phosphorylation status of Cx 43 was determined by Western blot analysis.
      RESULTS: The optimal noncytotoxic concentration of EGCG was determined to be 10
      microg/ml. The levels of GJIC and Cx 43 expression were markedly decreased in
      MDCK cells exposed to dimethylnitrosamine. A 12-h pretreatment with EGCG greatly
      ameliorated the GJIC-inhibitory effects of dimethylnitrosamine. CONCLUSION: These
      results suggest that the preservation of GJIC may indicate the chemopreventive
      effect of green tea on renal epithelial cells treated with a renal carcinogen in
      vitro.

PMID- 15736409
TI  - Antitumor effects produced by transduction of dendritic cells-derived
      heterodimeric cytokine genes in murine colon carcinoma cells.
AB  - Interleukin (IL)-23 and IL-27 have been recently identified as members of the IL
      12 heterodimeric cytokine family. The cytokines are released from activated
      dentritic cells and play a crucial role in cell-mediated immunity. Expression
      profiles of the cytokines' receptors suggest that target cells of the cytokines
      are distinct depending on T cell maturation and differentiation. We first
      examined whether murine colon carcinoma cells (Colon 26) expressing IL-27 (Colon
      26/IL-27) could produce antitumor effects in syngeneic mice. The mice developed
      small Colon 26/IL-27 tumors and subsequently rejected them, whereas parent tumors
      continued to grow. Since Colon 26/IL-12 and Colon 26/IL-23 cells were also
      rejected in syngeneic mice, we then investigated the combinatory antitumor
      effects of the cytokines. We inoculated Colon 26/IL-12, Colon 26/IL-23, Colon
      26/IL-27 cells or mixed populations of the cytokine producers into one flank of
      the mice that simultaneously received parent tumors in the other flank. The
      parent tumor growth influenced by the cytokine producers was similar to each
      other. Combinatory antitumor effects were not produced by the cytokine producers
      and application of the cytokines did not show any synergistic effects.

PMID- 15736410
TI  - Head and neck squamous cell carcinoma cell lines are highly sensitive to the new
      taxanes, BMS-184476, BMS-188797, in vitro.
AB  - BACKGROUND: The development of synthetic taxanes targets at increasing solubility
      of the drug, improved clinical efficacy and reduced side-effects. We evaluated
      the sensitivity of head and neck squamous cell carcinoma cell lines to BMS-184476
      and BMS-188797 in vitro. MATERIALS AND METHODS: The effects of paclitaxel and the
      synthetic taxanes were tested on six recently established cell lines (3 oral
      cavity SCC, 3 laryngeal SCC) using the 96-well plate clonogenic assay. The IC50
      values, corresponding to the mean inactivation dose, were obtained from the dose
      response curves. RESULTS: All tested cell lines were considerably more sensitive
      to both synthetic taxanes compared to paclitaxel. As a rule, the IC50
      concentration for paclitaxel was 4-5.5 times higher than that of BMS-184476 or
      BMS-188797. The sensitivity to these drugs varied from cell line to cell line,
      and time lapse video microscopy showed a mitotic arrest with subsequent apoptosis
      after four hours with BMS-188797. CONCLUSION: These results indicate that the
      synthetic taxanes could be useful clinically and warrant in vitro testing in
      combined modality models, like concurrent chemoradiation.

PMID- 15736411
TI  - Synthesis and antiproliferative activity of [1,2,4]triazino [4,3-a] indoles.
AB  - A series of [1, 2, 4triazino[4,3-a]indoles was prepared in good yield by reacting
      2-diazo-3-ethoxycarbonylindole with methylene active compounds. Derivatives of
      the title ring system were tested against a panel of 60 human tumor cell lines,
      and showed inhibitory activity against a wide range of cancer cell lines at
      micromolar concentration.

PMID- 15736412
TI  - Quantification of the expression of multidrug resistance-related genes in human
      tumour cell lines grown with free doxorubicin or doxorubicin encapsulated in
      polyisohexylcyanoacrylate nanospheres.
AB  - Doxorubicin (dox) encapsulated in polyisohexylcyanoacrylate nanospheres (PIHCA
      dox) can circumvent P-glycoprotein-mediated multidrug resistance (MDR). In order
      to investigate whether this drug formulation is able to select MDR cells in
      culture in the same way as free doxorubicin does, two human tumour cell lines,
      K562 and MCF7, were grown with increasing concentrations of either free dox or
      PIHCA-dox. For both drug formulations and for each selection level, the cell
      lines were more resistant to free dox than to PIHCA-dox. The MCF7 sublines
      selected with PIHCA-dox exhibited a higher level of resistance to both
      doxorubicin formulations than those selected with free doxorubicin. Different
      levels of overexpression of several genes involved in drug resistance (MDR1,
      MRP1, BCRP and TOP2alpha) occurred in the resistant variants. MDR1 gene
      overexpression was consistently higher in free dox-selected cells than in PIHCA
      dox-selected cells, while this was the reverse for the BCRP gene. Overexpression
      of the MRP1 and TOP2alpha genes was also observed in the selected variants. Our
      results show that several mechanisms may be involved in the acquisition of drug
      resistance and that drug encapsulation markedly alters or delays these processes.

PMID- 15736413
TI  - Effect of cyclooxygenase-2 antisense oligodeoxyribonucleotides in A-549 lung
      cancer cells.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 is overexpressed in several tumor entities and
      seems to play a key role in carcinogenesis. This makes it a potential target in
      cancer therapy. MATERIALS AND METHODS: Twelve phosphorothioate-modified antisense
      oligonucleotides (asODNs) against six targets of COX-2 mRNA were transfected to A
      549 lung carcinoma cells. COX-2 mRNA and protein levels were determined by
      quantitative RT-PCR and flow cytometry, respectively. Cell growth was assessed by
      measuring Alamar Blue reduction. RESULTS: The tested asODNs exhibited a range of
      activities. The most potent asODN reduced uninduced COX-2 mRNA to 66% and protein
      level to 75%, respectively. While this asODN did not influence cell growth, a 15%
      growth reduction was observed after transfection of another asODN which
      suppressed COX-2 mRNA to 71% and protein level to 84%. CONCLUSION: The use of
      asODNs directed against COX-2 mRNA is a promising approach to inhibit COX-2
      expression in tumor cells.

PMID- 15736415
TI  - Prevention of radiation-induced central nervous system toxicity: a role for
      amifostine?
AB  - PURPOSE: To review the role of amifostine (WR-2721) in ameliorating radiation
      induced central nervous system (CNS) toxicity. MATERIALS AND METHODS: Literature
      review and presentation of preliminary animal experiments designed to test the
      efficacy of both intrathecal and subcutaneous application of amifostine. RESULTS:
      Despite its inability to cross the blood-brain barrier, amifostine appears
      promising because it protects blood vessels against radiation-induced damage.
      Vascular damage is one of the most important components in the development of CNS
      toxicity after radiotherapy. Furthermore, the increased permeability of the blood
      brain barrier during fractionated radiotherapy might allow penetration of
      amifostine. Three animal studies with systemic administration found positive
      results after brain irradiation with different fractionation schedules, total
      doses and amifostine doses. One study where amifostine was given after
      radiotherapy showed no protection, suggesting that the timing of the drug
      application is crucial. Further data suggest that either intrathecal or systemic
      administration might protect the spinal cord as well. In our experience with
      spinal cord irradiation, systemic administration was more effective than
      intrathecal. Regarding CNS protection, the optimum dose of amifostine has yet to
      be determined. CONCLUSION: Several independent experiments provided preliminary
      evidence that modulation of the radiation response of the CNS in vivo by systemic
      administration of amifostine is possible and feasible. Additional studies are
      warranted to investigate the protective effect with differing regimens of
      administration, more clinically relevant fractionation regimens and longer follow
      up.

PMID- 15736414
TI  - Cellular and molecular effects of alpha-tocopheryloxybutyrate: lessons for the
      design of vitamin E analog for cancer prevention.
AB  - alpha-Tocopherol and its synthetic derivative, a-tocopheryl succinate (alpha-TS),
      are known to inhibit proliferation of cancer cells. alpha-TS is considered a more
      desirable anticancer agent because of the ability to induce apoptosis. It has
      been established previously that the whole intact alpha-TS molecule is necessary
      for its pro-apoptotic activity. For this reason, alpha-TS is not suitable for
      oral use because the ester bond linking succinate to tocopherol is subject to
      hydrolysis by intestinal esterases. One approach to overcome this problem is to
      replace the ester bond with an ether bond, since the latter is resistant to
      esterase-mediated hydrolysis. alpha-Tocopheryloxybutyrate (alpha-TOB) is the
      ether analog of alpha-TS. In this study, we compared the potency of alpha-TS and
      alpha-TOB using a panel of bioassays: cell growth, TUNEL labelling for apoptosis,
      PARP cleavage, caspase-3 and caspase-9 activation, as well as Akt and JNK
      phosphorylation. The experiments were carried out in two human prostate cancer
      cell lines: LNCaP and PC-3. Our results showed that alpha-TOB was capable of
      inhibiting cell growth and inducing apoptosis, although alpha-TOB was less active
      than alpha-TS on an equimolar basis. In general, it took twice as much alpha-TOB
      as alpha-TS to achieve the same response. Nonetheless, these two compounds shared
      the same mechanism of targeting the Akt and JNK signaling pathways, and
      activating the intrinsic cell death mediators of caspase-9 and caspase-3.
      Cellular analysis of alpha-TS and alpha-TOB showed that alpha-TOB was taken up as
      efficiently as alpha-TS (if not more so), suggesting that the lower activity of
      alpha-TOB is an inherent property of the molecule and not due to impaired uptake.
      Additional evidence is provided to show that beta-TS may act at the membrane
      level to interfere with Akt phosphorylation, although the exact nature of this
      disruption remains unclear. The future design of new anticancer tocopherol
      analogs should incorporate the ether linkage of the side chain for esterase
      resistance as well as other structural modifications for enhanced blocking of
      membrane signaling.

PMID- 15736416
TI  - Expression of the Drosophila melanogaster S3 ribosomal/repair protein in T24
      human bladder cells.
AB  - Repair of 8-oxo-7,8-dihydroguanine (8-oxoG) is inefficient in human cells due to
      the poor catalytic properties of hOGG1, the major DNA glycosylase involved in the
      removal of this oxidized base. The S3 ribosomal/repair protein from Drosophila
      melanogaster (dS3) is endowed with a potent 8-oxoG glycolytic activity coupled
      with a beta, delta-AP lyase. In vitro repair experiments have shown that pure GST
      tagged dS3 can stimulate a > 40-fold increase in the rate of 8-oxoG repair by
      human cell extracts. In this study, we expressed dS3 fused to the Enhanced Green
      Fluorescent Protein (EGFP) in T24 human bladder cells in order to accelerate the
      repair of 8-oxoG in vivo. Limiting dilution and Fluorescence-Activated Cell
      Sorting (FACS) were used in an effort to isolate cells with elevated EGFP-dS3
      expression; however, the cells that were isolated invariably had severe growth
      impairment. Curiously, EGFP-dS3 expression was slightly increased after
      recovering cells from liquid nitrogen, but it was not possible under those
      conditions to achieve a significant acceleration of 8-oxoG repair. The data
      confirm and extend our previous results obtained with Chinese hamster CHO cells
      and indicate that elevated expression of dS3 may be toxic to at least some types
      of mammalian cells, thus limiting its use in vivo as a protective factor against
      oxidative DNA damage.

PMID- 15736418
TI  - Effect of lactoferrin on the methotrexate-induced suppression of the cellular and
      humoral immune response in mice.
AB  - Our previous studies revealed that lactoferrin (LF) reconstitutes the cellular
      and humoral immune response in cyclophosphamide-treated mice. The aim of this
      investigation was to establish whether the suppressory effects of methotrexate
      (MTX) on the cellular and humoral immune response can be modulated by LF. We
      found that MTX, given intraperitoneally (i.p.) at a dose of 200 mg/kg b.w., 48 h
      following sensitization of CBA mice with ovalbumin (OVA), reduced by 80% the
      delayed type hypersensitivity (DTH) response. Co-administration of LF in drinking
      water (0.5% solution) for the duration of the experiment (4 days) restored the
      DTH response almost to the control level. However, LF was not able to restore the
      primary humoral immune response, measured by the number of antibody-forming cells
      (AFC) to sheep erythrocytes (SRBC) in the spleens when MTX (1 mg/kg b.w.) was
      administered to mice i.p. 48h post immunization. On the other hand, mice treated
      with LF after second challenge with SRBC showed significant restoration of the
      MTX-suppressed humoral immune response following the booster immunization. In
      addition, LF (1 microg/ml) restored the secondary humoral immune response to SRBC
      in vitro when MTX (0.05-1 mM) was added to cell cultures on day 2 following cell
      culture initiation. These data demonstrate that LF preferentially restores the
      cellular immune response impaired by MTX treatment. It seems that LF also
      prevents the block of the activity of T memory cells in the secondary, humoral
      immune response. Taken together, we demonstrated that LF given orally can reduce
      the toxic effects of MTX.

PMID- 15736417
TI  - Analysis of central regulatory pathways in p53-deficient primary cultures of
      malignant fibrous histiocytoma exposed to ifosfamide.
AB  - Soft tissue sarcomas frequently carry p53 mutations reducing chemotherapeutical
      response. Especially malignant fibrous histiocytoma (MFH) reveals a reduced
      ifosfamide (IF) chemosensitivity when compared to other sarcoma entities. This is
      the first study to analyze MFH cells for the effects of IF on the expression of
      the pathways P16-CDK4-Rb and P14ARF-MDM2-P73 regulating cell cycle. The aim was
      to identify candidate genes possibly involved in the anti-apoptotic response of
      p53-deficient MFH cells during chemotherapy. PCR, real-time RT-PCR and confocal
      laser scanning microscopy were applied on primary cultures of MFH cells
      containing defective p53 genes. The cultures were treated with different
      concentrations of IF. A non-treated MFH culture served as negative control. A
      threshold concentration of IF (100 microM) was determined sparing the majority of
      the cells (99%), whereas higher IF quantities caused complete apoptosis. Data
      collected over a period of 48 h showed that the MFH cells surviving 100 microM IF
      overexpressed the kinase gene CDK4 and oncogene MDM2 by a factor of 63. A similar
      strong increase was observed at the protein level for both proteins. In contrast,
      the other proteins analyzed were not detectable. Additionally, the MFH cells
      induced complex patterns of MDM2 mRNA splicing and an abnormal mRNA transcript
      carrying a novel MDM2 missense mutation. These effects were neither observed in
      the non-treated culture nor in cultures completely inducing spontaneous
      apoptosis. Therefore, we speculate that the induction of the gene CDK4, and
      especially of MDM2, is involved in anti-apoptotic mechanisms of p53-negative MFH
      cells tolerating IF in vitro. Further experiments are necessary to test whether
      the novel candidate genes favor development of chemoresistance and whether MDM2
      mRNA splicing variants contribute to this process in vivo.

PMID- 15736419
TI  - Up-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in left
      sided human colon cancer.
AB  - BACKGROUND: We evaluated the HMGCoA reductase activity and LDL receptor levels in
      human colon cancer as well as the effects of simvastatin on in vitro cell growth
      and apoptosis of DLD-1 and Caco2 cell lines. MATERIALS AND METHODS: HMGCoA
      reductase activity and LDL receptor were measured by radiochemical assay and
      ELISA method, respectively. Cell growth and apoptosis were evaluated by MTT-test
      and DNA fragmentation analysis, respectively. RESULTS: Higher HMGCoA reductase
      activity and LDL receptor levels were detected in cancer than in normal mucosa.
      An up-regulation of HMGCoA reductase activity was detected in left-sided tumors.
      Simvastatin treatment produced marked anti-proliferative and pro-aptotic effects
      in DLD-1. Cell growth inhibition, but no apoptosis, was also evident in Caco2
      cells. CONCLUSION: The cholesterol pathway is involved in colon malignant
      transformation. Therapeutic strategies using HMGCoA reductase inhibitors as anti
      cancer compounds should also take into consideration the biological and clinical
      differences detected inside colon tracts.

PMID- 15736420
TI  - Immunohistochemical expression of E-cadherin and beta-catenin in the normal and
      malignant human endometrium: an inverse correlation between E-cadherin and
      nuclear beta-catenin expression.
AB  - BACKGROUND: The E-cadherin/beta-catenin complex plays a crucial role in
      epithelial cell-cell adhesion and in the maintenance of tissue architecture. We
      previously reported aberrant expression of beta-catenin in endometrial
      carcinomas. However, the expression and correlation of E-cadherin and beta
      catenin in normal and malignant endometrial tissues are not fully understood.
      MATERIALS AND METHODS: Immunohistochemical expression of E-cadherin and beta
      catenin was detected in 30 cases of normal endometrium and 73 cases of
      endometrial carcinoma. RESULTS: In the normal endometrium, the expression of E
      cadherin and cytoplasmic beta-catenin in glandular cells was predominantly
      observed in the proliferative phase, and decreased in the secretory phase. In
      endometrial carcinomas, the expression of E-cadherin and cytoplasmic beta-catenin
      decreased compared to that in the normal proliferative endometrial glands. The
      expression of E-cadherin and cytoplasmic beta-catenin tended to be reduced in
      histologically high-grade tumors compared to low-grade tumors. Nuclear expression
      of beta-catenin was observed in the glandular cells in the late proliferative and
      early secretory phases, as well as in high-grade endometrial carcinomas.
      Interestingly, nuclear beta-catenin expression was associated with the loss of E
      cadherin expression in normal and carcinoma cells, indicating an inverse
      correlation. CONCLUSION: The cyclic expression of E-cadherin and beta-catenin in
      the normal endometrium suggests that the adhesion complex may act to maintain the
      endometrial architectures. In addition, nuclear beta-catenin expression
      associated with loss of E-cadherin expression may be involved in the acquisition
      of aggressive biological behavior, especially in high-grade tumors.

PMID- 15736421
TI  - Expression of twist and wnt in human breast cancer.
AB  - Twist, a transcription factor of the basic helix-loop-helix class, has been
      suggested to have oncogenic properties. We reported Twist expression was
      regulated by Wnt/beta-catenin signaling and that both Wnt-1 and Twist could
      contribute to mammary tumorigenesis. The aim of this study was to demonstrate the
      expression of Twist, Wnt-1 and Wnt-2 in human breast cancer tissue. We examined
      the expression in patients with breast cancer by RT-PCR and immunohistochemistry.
      RT-PCR of twenty-three pairs of cancer and normal breast tissue revealed that
      Twist was up-regulated in 69.6% (16/23) of the cancer lesions and 21.7% (5/23) of
      the normal breast tissues. Wnt-2 was up-regulated in all of the cancer lesions
      and 13.0% (3/23) of the normal breast tissues, whereas Wnt-1 was expressed in
      both the cancer and normal breast tissues of the five cases examined.
      Immunohistochemical analyses revealed that Twist was positively expressed in
      52.2% (12/23) of the cancer lesions and 34.8% (8/23) of the normal breast
      tissues. Twist and Wnt-2 are highly expressed in breast cancer tissue, suggesting
      that both molecules could play important roles in mammary carcinogenesis.

PMID- 15736422
TI  - Numerical aberrations of chromosomes 9 and 11 detected by FISH in Greek bladder
      cancer patients.
AB  - BACKGROUND: Bladder cancer is a genetically heterogeneous disease. The
      chromosomal aberrations observed are non-random and they are often correlated
      with disease progression. Several environmental risk factors have also been
      reported to be implicated in the pathogenesis of this disease. The aim of this
      study was to evaluate, by FISH technique, the numerical aberrations of
      chromosomes 9 and 11 in Greek bladder cancer patients and to correlate them with
      grade and histological stage of the tumors. MATERIALS AND METHODS: FISH with a
      satellite DNA probes specific for chromosomes 9 and 11 were applied to 35 primary
      bladder tumors directly processed for cytogenetic study. RESULTS: Numerical
      aberrations of chromosome 9 were observed in 23 out of 27 tumors (85.18%).
      Monosomy 9 was detected in 12 cases (44.45%) and polysomy in 11 cases (40.74%).
      Statistical analysis showed that polysomy 9 was linked to histological stage (p =
      0.024) and grade (p = 0.01) of the tumors, while monosomy 9 was correlated with
      tumor stage (p = 0.050). Numerical aberrations of chromosome 11 were observed in
      25 out of 35 cases (71.43%). Polysomy was detected in 24 cases (68.57%), while
      only one case (2.86%) had monosomy 11. Polysomy 11 was found mainly in high-grade
      and advanced-stage tumors. CONCLUSION: Numerical aberrations of chromosome 9
      could be a potential biomarker for bladder cancer screening. Further studies must
      be carried out to investigate gene alterations reflected by numerical aberrations
      of chromosomes 9 and 11 also contributing to the classification of this disease.

PMID- 15736423
TI  - The MTHFR C677T polymorphism, estrogen exposure and breast cancer risk: a nested
      case-control study in Taiwan.
AB  - BACKGROUND: We evaluated the effects of the MTHFR C677T polymorphism and its
      interaction with estrogen exposure on breast cancer risk in a nested case-control
      study conducted in Taiwan. MATERIALS AND METHODS: A total of 88 histologically
      confirmed breast cancer cases and 344 cancer-free controls were recruited between
      July 1992 and December 2000. The MTHFR C677T genotype was determined by a PCR
      RFLP-based assay. All subjects completed in-person interviews. RESULTS: There was
      a significant trend of breast cancer in relation to prolonged exposure to
      estrogens prior to the first full-term pregnancy (FFTP) (p for trend = 0.0015).
      In contrast, there was no statistically significant association between the risk
      of breast cancer and the MTHFR C677T genotype. However, a significantly elevated
      risk of breast cancer predisposed by the MTHFR 677T variant genotype (CT and TT)
      was observed in women with prolonged exposure to estrogens prior to FFTP
      (adjusted OR = 4.98, 95% CI = 2.00-12.43). CONCLUSION: The results of this study
      suggest that the MTHFR 677T variant genotype per se may have no overall
      association with breast cancer risk, but a sizable association could be observed
      in the presence of relevant environmental exposure.

PMID- 15736424
TI  - Change of zinc uptake under growth arrest and apoptosis.
AB  - Zinc uptake is critical for cell proliferation. On the basis of the evidence that
      brain tumors are positively-imaged with 65Zn, cellular zinc uptake was studied
      under growth arrest and apoptosis to understand the relationship between cellular
      viability and zinc uptake. When NIH3T3 cells were cultured in albumin-coated
      dishes under the presence of serum, the viability of the cells detached from the
      extracellular matrix, which was determined with fluoresceine diacetate, was
      almost the same as the control cells cultured in untreated dishes. Both the
      uptake of 14C-thymidine and 65Zn by the cells was significantly suppressed by
      detachment from the extracellular matrix, suggesting that cellular zinc uptake is
      suppressed by growth arrest. When apoptosis was induced in the cells detached
      from the extracellular matrix under serum-free condition, 65Zn uptake by the
      cells led to apoptosis which was significantly higher than that by the control
      cells. 65Zn uptake by C6 glioma cells, which were irradiated with gamma-ray, was
      also higher than that by control (unirradiated) C6 glioma cells. The present
      study demonstrates that zinc uptake is involved not only in the process of cell
      proliferation, but also in the process of apoptosis.

PMID- 15736425
TI  - Thymidylate synthase gene promoter polymorphisms are associated with TSmRNA
      expressions but not with microsatellite instability in colorectal cancer.
AB  - BACKGROUND: Microsatellite instability (MSI) is a biological characteristic of
      most tumours, being involved in 85% of hereditary non-polyposis colorectal cancer
      (HNPCC). It also occurs in 10-15% of sporadic colorectal cancers (CRC). HNPCC
      appears to be caused by germline mutations in mismatch repair (MMR) genes, which
      are responsible for repairing single base-pair mismatches. MSI is also associated
      with a better response of CRC to adjuvant chemotherapy with fluoropyrimidines. We
      investigated any relationship between the MSI status and the TSmRNA expression,
      the polymorphisms of 5-Fluorouracil (5-FU cellular target, the enzyme thymidylate
      synthase (TS) and TS expression evaluated by means of immunohistochemistry.
      MATERIALS AND METHODS: A series of 80 colorectal cancers was evaluated for MSI
      and polymorphisms in the 3'UTR and the 5'UTR of the TS gene by a PCR assay.
      TSmRNA was quantified by real-time PCR and the TS expression by
      immunohistochemical assay. RESULTS: There was no significant association between
      the polymorphisms in the TS gene and the MSI or between the TSmRNA expression and
      the MSI status. CRC with a 3R/3R or 2R/3R genotype showed a significantly higher
      TSmRNA expression than those with the 2R/2R genotype (p = 0.001 and p = 0.028,
      respectively). Another significant association was found between the TSmRNA
      expression and the TS immunohistochemical determination (p = < 0.05). No
      association was found between the polymorphism of the 3'UTR and the TSmRNA
      expression. CONCLUSION: Our data show that there is no association between MSI
      status and the polymorphisms in the 3' and 5' UTRs and the TS expression. Tumour
      samples displaying the 3R/3R or 2R/3R genotype of TS have higher TSmRNA levels
      than the 2R/2R genotype. Polymorphic variant of the 3'UTR does not influence the
      TSmRNA level. We found a relationship between the TSmRNA expression, evaluated by
      real-time PCR, and with the TS level determined by immunohistochemical assay.
      Thus, genotyping of the 5'UTR and quantification of the TSmRNA expression in
      human CRC could be considered as predictors for response to SFU-based
      chemotherapy. The evaluation of the TS expression by means of
      immunohistochemistry assay remains a safe and reliable assay in CRC.

PMID- 15736426
TI  - STAT 3 activation in head and neck squamous cell carcinomas is controlled by the
      EGFR.
AB  - Proliferation of squamous cell carcinoma of the head and neck (SCCHN) depends on
      epidermal growth factor receptor (EGFR) expression. As STAT 3 activation as well
      contributes to the cell growth in SCCHN, the interaction of STAT 3 and the EGFR
      is of great interest when considering treatment options through inhibition of
      STAT 3. We, therefore, evaluated the influence of blocking or activating the EGFR
      in human SCCHN cell lines and in vivo tumors on STAT 3 activation. We compared
      the effects on STAT 3 activation with the regulation of MAP Kinase under these
      conditions. We found that STAT 3 can be strongly inhibited via EGFR blocking in
      vitro as well as in vivo. However, the influence of EGFR regulation on the MAP
      Kinase pathway seemed to be very slight. These findings provide evidence that
      STAT 3 signal activity in head and neck carcinomas, which is partially
      responsible for proliferative activity, can be controlled via the EGFR.

PMID- 15736427
TI  - Sp1 regulates cathepsin B transcription and invasiveness in murine B16 melanoma
      cells.
AB  - BACKGROUND: Increased expression of cathepsin B contributes to extracellular
      matrix degradation and invasion in cancer. Cathepsin B expression is under
      transcriptional control in murine melanomas and the major promoter contains
      potential binding sites for the Sp1 transcription factor. MATERIALS AND METHODS:
      Murine melanoma cells transfected with an Sp1 expression plasmid or its control
      were used in Matrigel invasion and cell motility assays in the presence or
      absence of the cathepsin B inhibitor, CA-074Me. RESULTS: Transfection of B16F1
      cells with the Sp1 expression plasmid resulted in a 2.5- to 5.3 -fold increase in
      cathepsin B specific activity and a 4.8- to 5.5-fold increase in invasiveness
      over the control, but had no effect on the movement of cells across an uncoated
      membrane. CA-074Me treatment resulted in significantly reduced Matrigel invasion
      without affecting cell motility. CONCLUSION: Sp1 can regulate the capacity of
      B16F1 cells to degrade a reconstituted extracellular matrix in part by regulating
      cathepsin B expression.

PMID- 15736428
TI  - Cisplatin down-regulates topoisomerase I activity in lung cancer cell lines.
AB  - Many clinical studies have reported that irinotecan has reproducible antitumor
      activity against lung cancer. Both cisplatin and SN-38 are key drugs in the
      treatment of lung cancer, and their combination is one of the most promising
      regimens available. Using lung cancer cell lines, ABC-1 and SBC-3, we examined
      the cytotoxic effect of the schedule, as well as the effect of cisplatin on
      topoisomerase I activity. Cytotoxicity was determined by MTT assay. ABC-1 or SBC
      3 cells were incubated with or without various concentrations of both drugs in 96
      well microplates for 72 or 96 hours in a humidified 5% CO2 atmosphere at 37
      degrees C. Synergism was evaluated by median-effect plot analysis and a
      combination index isobologram method by Chou and Talalay. After ABC-1 or SBC-3
      cells had been exposed to 10/microM cisplatin for one hour, topoisomerase I
      activities were determined by supercoiled-DNA relaxation assay. Synergism was
      observed in ABC-1 and SBC-3 cells when cisplatin was given first, followed by SN
      38 (7-ethyl-10-hydroxycamptothecin) and cisplatin. Topoisomerase I activity
      decreased at 1-2 hours after exposure to cisplatin and recovered gradually after
      4-5 hours of cisplatin exposure in both ABC-1 and SBC-3 cells. Accordingly,
      pretreatment with cisplatin will have an impact on the sensitivity to SN-38.

PMID- 15736429
TI  - Functional analysis of focal adhesion kinase (FAK) reduction by small inhibitory
      RNAs.
AB  - The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes
      to the points of cell contact with the extracellular matrix, called focal
      adhesions. Many factors induce tyrosine phosphorylation of FAK including growth
      factors, neuropeptides and integrin-dependent adhesion to the extracellular
      matrix. FAK has been implicated in several cellular processes such as invasion,
      motility, proliferation and apoptosis. In addition, FAK expression was shown to
      be elevated in a number of different human cancers, suggesting a role in the
      development of malignancy. We examined the biological functions of FAK using
      small inhibitory RNAs (siRNA) in cancer cells. Although FAK siRNA reduced the FAK
      protein levels by approximately 70% in several cancer cell lines, there was no
      clear evidence of apoptosis. However, in clonogenic and soft-agar assays in
      H1299, a lung cancer cell line, FAK siRNA treatment led to a 43% to 55% decrease
      in colony formation. Furthermore, FAK siRNA-treated cells displayed a decrease in
      migration when serum or EGF (epidermal growth factor) were used as chemo
      attractants. Our results demonstrated that inhibition of FAK protein leads to
      alterations in cell growth and migration.

PMID- 15736430
TI  - Chkl binds and phosphorylates BAD protein.
AB  - Chk1 (checkpoint kinase 1) is a serine-threonine kinase that is critical for G2/M
      arrest in response to DNA damage. Chk1 phosphorylates Cdc25C at serine-216, a
      major regulatory site, in response to DNA damage. Furthermore, Chk1 also
      phosphorylates Cdc25A on serine 123 which accelerates its degradation through the
      ubiquitin-proteasome pathway and arrests cells in late G2-phase after DNA damage.
      In the present study, we demonstrated that Chk1 phosphorylates pro-apoptotic
      protein BAD (Bcl-2/Bcl-XL-Antagonist, causing cell Death) in vitro. In vitro
      phosphorylation analysis with various mouse BAD peptides has revealed two
      phosphorylation sites for Chk1 at serine-155 and serine-170. When wild-type and
      mutant BAD (S155A) constructs were transfected into 293T cells, an association
      between BAD and Chk1 was observed by co-immunoprecipitation. In addition, there
      was an increase in the phosphorylation of serine-155 following DNA damage by
      adriamycin treatment. Our results suggest that Chk1 associates with BAD and
      phosphorylates the BAD protein at serine-155. Taken together, our results suggest
      that Chk1 may inactivate BAD by associating with and phosphorylating residues
      critical for BAD function in response to DNA damage.

PMID- 15736431
TI  - Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung
      cancer cell line.
AB  - Irinotecan is one of the most active drugs used in the treatment of small cell
      lung cancer (SCLC). 7-Ethyl-10-hydroxy-camptothecin (SN-38) is an active
      metabolite of irinotecan. We established an SN-38-resistant subline (SBC-3/SN-38)
      by continuous exposure of SN-38 to a human SCLC cell line, SBC-3. Using the 3-[4,
      5-dimethyl-thiazol-2-yl] 2, 5-diphenyltetrazolium bromide assay, we evaluated the
      cytotoxicity of 17 anticancer agents. The SBC-3/SN-38 cells were 73-fold more
      resistant than the parental SBC-3 cells to SN-38 and showed cross-resistance not
      only to topoisomerase (topo) I inhibitors (irinotecan and topotecan), but also to
      topo II inhibitors (adriamycin and etoposide), antimicrotubule agents
      (vincristine, vindesine, vinorelbine and docetaxel), alkylating agents
      (cyclophosphamide and ifosfamide), platinum (cisplatin and carboplatin) and
      antifolate (methotrexate). Interestingly, the resistant subline reserved the
      sensitivity to bleomycin and 5-fluorouracil. The SBC-3/SN-38 cells had decreased
      topo I and II activity compared to the parent cells. The SN-38-resistant cell
      line, SBC-3/SN-38, will be useful to elucidate the mechanism of action of the
      topo I inhibitors.

PMID- 15736432
TI  - Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by
      tropolones.
AB  - We investigated the effect of 27 tropolones on nitric oxide (NO) production by
      mouse macrophage-like Raw 264.7 cells. All of these compounds failed to stimulate
      the Raw 264. 7 cells to produce detectable amounts of NO, but inhibited NO
      production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to various
      extents. Generally, the ability of tropolones to inhibit LPS-stimulated NO
      production was inversely related to their cytotoxic activity. Western blot and RT
      PCR analyses demonstrated that the most active compound, 2,4-dibromo-7
      methoxytropone [21], significantly reduced both the intracellular concentration
      of iNOS protein and the expression of iNOS mRNA. ESR spectroscopy showed that
      [21] did not produce radicals under alkaline condition, nor scavenged NO,
      produced by NOC-7. These data suggested that the inhibitory effect of [21] on NO
      production might be generated via the inhibition of iNOS expression, rather than
      a radical-mediated mechanism.

PMID- 15736433
TI  - Characterization of the glutametergic system in MG-63 osteoblast-like
      osteosarcoma cells.
AB  - BACKGROUND: The glutamate system is a fairly complex bioregulation pathway,
      consisting of several ionotropic Glu receptors (iGlu.Rs), the metabotropic Glu
      receptors (mGlu.Rs), Glu transporters (EAATs) and glutamine synthetase (GS),
      which metabolizes glutamate to glutamine. MATERIALS AND METHODS: We characterized
      the MG-63 human osteoblast-like osteosarcoma cells with regards to mRNA
      expression of the (a) NMDA.R group of iGlu.Rs, (b) mGlu.Rs, (c) EAAT1
      transporter, and (d) GS, using specific primers for their detection by RT-PCR.
      RESULTS: Our data confirm the mRNA expression of the NR1, NR2A, NR2B and NR2D
      subunits of NMDA.R and of GS mRNA in MG-63 cells. In addition, we documented, for
      the first time, the mRNA expression of the NR3A, EAAT1, mGlu.R1, mGlu.R2,
      mGlu.R3, mGluR.4, mGlu.R5 and mGlu.R8 mRNA. However, we did not detect the mRNA
      expression of NR2C, NR3B, mGlu.R6 and mGlu.R7 mRNA. CONCLUSION: Our data suggest
      that MG-63 cells can be used as a model for studying the possible role of Glu
      beyond CNS.

PMID- 15736434
TI  - Kinetic studies of the radical-scavenging activity of estrogens and
      antiestrogens.
AB  - Quinoids, quinoid radicals and phenoxyl radicals formed from estrogens (estrone;
      diethylstilbestrol, DES) and antiestrogens (tamoxifen; toremifene) may be
      responsible for adverse effects such as carcinogenesis. The radical-scavenging
      activity of estrogens and antiestrogens was determined quantitatively by the
      induction period method for the polymerization of methyl methacrylate initiated
      by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) or benzoyl
      peroxide (BPO) under nearly anaerobic conditions. The inhibition rate constant
      (k(inh), x10(-3) M(-1)s(-1)) for estrone, DES, tamoxifen, toremifene and 2,6-di-t
      butyl-4-methyphenol (BHT) was 1-3, 2-4, 6-12, 6-13 and 1-2, respectively. The
      k(inh) for antiestrogens was two-fold greater than that for estrogens or BHT. In
      contrast, the stoichiometric factor (n, number of free radicals trapped by one
      mole of antioxidant moiety) for estrone, DES, tamoxifen, toremifene and BHT was
      1.2-1.5, 1.8-2.4, 0.5-0.9, 0.4- 0.5 and 1.5-1.9, respectively. The fully oxidized
      n values for estrone, DES and BHT would be 2, whereas that for antiestrogens
      would be 1. However, the n values for estrone and antiestrogens were markedly
      less than 2 and 1, respectively, suggesting a complex oxidation process resulting
      in the formation of quinoids, quinoid radicals and phenoxyl radicals during the
      induction period.

PMID- 15736436
TI  - Conventional cytogenetics and fluorescence in situ hybridization in persistent
      cytopenias and myelodysplastic syndromes in childhood.
AB  - Accurate detection of the abnormal clone in children with persistent cytopenia
      (PC) may confirm the diagnosis of myelodysplastic syndrome (MDS) and determine
      prognosis and evolution of the disease. Bone marrow (BM) samples were obtained
      from 65 children, 11 of which were finally diagnosed as primary or secondary MDS.
      Ten to 20 G-banded metaphases were analyzed and FISH was performed using a
      satellite probes for chromosomes 7 and 8. Conventional cytogenetic analysis (CCA)
      was successful in 40/65 samples, revealing clonal aberrations in 3 patients with
      MDS. FISH was successful in all cases, detecting monosomy 7 and trisomy 8
      abnormal clones in 5 patients. Abnormalities were identified in 3/6 children with
      primary MDS and 3/5 with secondary MDS. None of the patients with PC of etiology
      other than MDS had a clonal abnormality in the BM. The results confirm the high
      incidence of chromosome abnormalities in childhood MDS and the sensitivity of
      FISH in detecting minor abnormal clones.

PMID- 15736435
TI  - Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by
      azulenes.
AB  - We investigated the effect of twenty-seven azulenes on nitric oxide (NO)
      production by mouse macrophage-like Raw 264.7 cells. No azulene derivative alone
      induced NO production by the Raw 264.7 cells, but inhibited lipopolysaccharide
      (LPS)-stimulated NO production to various extents. The ability of azulenes to
      inhibit NO generation by activated macrophages was generally increased when their
      cytotoxic activity declined. Western blot and RT-PCR analyses demonstrated that
      the most potent compound, 1,3-difluoroazulene [11], slightly inhibited the
      expression of inducible NO synthase (iNOS), but only at extremely high
      concentrations. ESR spectroscopy showed that [11] did not produce radical under
      alkaline condition, nor scavenged O2- (generated by HX-XOD reaction) or NO
      (generated by NOC-7). These data suggest that the inhibitory effect of [11] may
      be produced via a mechanism other than iNOS induction and a radical-mediated
      mechanism.

PMID- 15736437
TI  - Over-expression of RNA helicases in cancer.
AB  - RNA helicases constitute a large group of essential enzymes involved in all
      aspects of RNA metabolism. With few exceptions, human RNA helicases of DDX and
      DHX gene families have not been well characterized. However, several of them have
      been shown to be dysregulated in cancer, including over-expression in various
      types of tumors. Although the exact contribution of RNA helicases to
      carcinogenesis has not been determined, their over-expression in cancer render
      them potential targets for novel anti-cancer agents. In this review, RNA
      helicases whose expression is up-regulated in cancer are highlighted.

PMID- 15736438
TI  - Checkpoint effectors CDKN1A and Gadd45 correlate with oxidative DNA damage in
      human prostate carcinoma.
AB  - BACKGROUND: Although cellular oxidative stress is a major cause of DNA damage, it
      is still not clear to what degree it affects genetic instability and malignant
      progression in established prostate carcinoma (PCa). MATERIALS AND METHODS: We
      examined the expression of CDKN1A and Gadd45 proteins acting on cell cycle
      checkpoints and DNA repair in PCa relative to the presence of oxidative DNA
      damage, as measured by the detection of the DNA adduct 8-hydroxy-2-deoxyguanosine
      (8-OHdG.). Sixteen PCa and 28 benign prostate hyperplasias (BPH) were analyzed.
      RT-PCR was used to evaluate WAF1 and Gadd45 transcripts. Western blot and ELISA
      were used to analyze proteins and 8-OHdG adducts. Proliferation was studied by
      Ki67 image cytometry; telomerase activity was detected by TRAP- ELISA. RESULTS:
      Multivariate factor analysis provided evidence that, in PCa, DNA checkpoint
      proteins were associated with 8-OHdG and did not prevent neoplastic cells
      proliferation. Conversely, in BPH, oxidative DNA damage was inversely correlated
      with DNA checkpoint proteins and proliferation, suggesting the presence of energy
      depleted senescent cells. CONCLUSION: Although in non-malignant tissue extensive
      oxidative DNA damage drives cells to a metabolic blockage, in PCa neoplastic
      cells it activates repair mechanisms favoring the escape from senescence and the
      expansion of DNA-damaged clones.

PMID- 15736439
TI  - Effect of estrogen, tamoxifen and epidermal growth factor on the transcriptional
      regulation of vascular endothelial growth factor in breast cancer cells.
AB  - BACKGROUND: VEGF (Vascular Endothelial Growth Factor) is a key factor of
      angiogenesis and high tissue VEGF levels are related to a poor prognosis in
      breast cancer. MATERIALS AND METHODS: By semi-quantitative RT-PCR, we determined
      the relative expressions of VEGF mRNA in MCF-7 (both ER-alpha+ and ER-beta+
      (mainly ER-alpha+), PR+, bcl-2+, EGFR-) and MB-MDA-231 (only ER-beta+, PR-, EGFR
      ) breast cancer cells which were treated with estrogen, tamoxifen and EGF
      (Epidermal Growth Factor). RESULTS: In MCF-7 cell lines, estrogen induced the
      expression of VEGF mRNA while tamoxifen reduced its expression. Estrogen and
      tamoxifen did not confer any significant effect on MB-MDA-231 cells and EGF
      showed no significant effect on MCF-7 or MB-MDA-231. CONCLUSION: Reduced VEGF
      mRNA expression of MCF-7 cells treated with tamoxifen may be related to the
      antagonistic effect of tamoxifen on ER-positive breast cancer, and this
      antagonistic effect may be related to ER-alpha.

PMID- 15736440
TI  - Polymorphisms of glutathione-S-transferase and arylamine N-acetyltransferase
      enzymes and susceptibility to colorectal cancer.
AB  - BACKGROUND: Glutathione-S-transferases (GSTs) and N-acetyltransferases (NATs) are
      involved in the metabolism of a wide range of carcinogenic chemicals. Allelic
      polymorphism of these enzymes is associated with variations in enzyme activity,
      hence it may affect the concentration of activated carcinogenic chemicals in the
      body. Previous studies suggest a possible cancer risk-modifying effect of these
      allelic polymorphisms, but the results are still controversial. We evaluated the
      effect of GSTM1, GSTT1, GSTP1, NAT1 and NAT2 enzymes on individual susceptibility
      to colorectal cancer, with particular attention to possible interactions between
      the studied genotypes. MATERIALS AND METHODS: Five hundred colorectal cancer
      patients and 500 matched cancer-free controls were included in the study. The
      allelic polymorphisms of GSTM1, GSTT1 and GSTP1, NAT1 and NAT2 enzymes were
      determined by PCR-based methods, from peripheral blood leukocytes, and allelic
      distributions were compared between colorectal cancer patients and controls.
      RESULTS: The GSTM1 0 allele (OR: 1.48, 95% CI: 1.15-1.92) and rapid acetylator
      genotypes of NAT2 (OR: 1.52, 95% CI: 1.17-1.98) were associated with an elevated
      risk No statistically significant correlation between NAT1, GSTT1, GSTP1
      genotypes and colorectal cancer was found. Remarkably increased risk was
      associated with the GSTM1 0 allele--NAT2 rapid acetylator genotype combination
      (OR: 2.39, 95% CI: 1.75-3.26) and with the GSTM1 0 allele--NAT2 and NAT1 rapid
      acetylator triple combination (OR: 3.28, 95% CI: 2.06-5.23). Carrying 4 or 5
      putative "high-risk" alleles substantially increased the risk of colorectal
      cancer (OR: 3.69, 95% CI: 2.33-5.86). CONCLUSION: The genotype of certain
      metabolizing enzymes affects the risk for colorectal cancer. This effect is
      particularly important when certain allelic combinations are studied. In the near
      future, individual level risk assessment may be reached by further increasing the
      number of studied polymorphisms, combining them with traditional epidemiological
      risk factors.

PMID- 15736441
TI  - Action and efficacy of p-[131I]iodo-L-phenylalanine on primary human glioma cell
      cultures and rats with C6-gliomas.
AB  - BACKGROUND: Recently we demonstrated high selectivity and long retention of p
      [123I]iodo-L-phenylalanine (IPA-123) for diagnostic purposes in gliomas. Here we
      describe the potency of the iodine-131-labelled analogue p-[131I]iodo-L
      phenylalanine (IPA-131) for experimental treatment of gliomas. MATERIALS AND
      METHODS: Two human glioma cell cultures and 15/20 rats with C6-gliomas were
      exposed to IPA-131. RESULTS: After 24-h-exposure the cell number of the glioma
      cell cultures was reduced by 77% and 79%, respectively. Four out of five
      untreated rats died 8-24 days after implantation and had verifiable tumours.
      Seven animals died despite therapy, while 8 were soon healthier, gained body
      weight and were sacrificed 81 days after implantation, at which time survival of
      the treated animals was significantly prolonged (p < 0.05). At autopsy, instead
      of tumours there were substance defects, surrounded by pre-existing parenchyma
      infiltrated by probable tumour cells that were not discernible from reactive
      astrocytes, lymphocytes, monocytes and multinuclear giant cells. CONCLUSION: IPA
      131 has promising activity against human glioma cells in vitro and experimental
      gliomas in vivo.

PMID- 15736442
TI  - Is troponin I gene therapy effective for osteosarcoma treatment? Study on a human
      like orthotopic rat model.
AB  - BACKGROUND: An anti-angiogenesis strategy has been widely recognized as a viable
      approach to fight cancer and more and more anti-angiogenic factors are
      continually being identified. Among them, the muscular isoform of Troponin I
      (TnI) has been described as being a powerful anti-angiogenic agent in vitro as
      well as in vivo. We investigated the therapeutic efficacy of TnI gene therapy in
      a human-like orthotopic rat osteosarcoma model. MATERIALS AND METHODS: In this
      tumor model, we evaluated whether the administration of the secreted TnI coding
      sequence complexed to cationic liposomes (named TnITag cDNA/lCLP) could induce a
      delay in tumor growth and reduce tumor vasculature. RESULTS: Although TnI
      specifically inhibited endothelial cell growth in vitro, we were not able to
      demonstrate any therapeutic efficacy of TnI in the transplantable osteosarcoma
      model. CONCLUSION: This lack of efficacy probably resulted from the rapid
      degradation of recombinant TnI by matrix metalloproteinases, especially MMP2,
      which are present in large amounts in tumors.

PMID- 15736444
TI  - Anticancer activity of bacteriophage T4 and its mutant HAP1 in mouse experimental
      tumour models.
AB  - BACKGROUND: Previously, we have shown the ability of the bacteriophage T4 and its
      substrain HAP1 (selected for a higher affinity to melanoma cells) to reveal
      antimetastatic activity in a mouse melanoma model. Here, we investigated the
      potential phage anticancer activity in primary tumour models. MATERIALS AND
      METHODS: Mice were inoculated subcutaneously with B16 or LLC cells (collected
      from in vitro culture). Bacteriophages T4 and HAP1 were injected
      intraperitoneally daily (8 x 10(8)pfu/mouse, except the experiment concerning the
      dose-dependence). RESULTS: Treatment with purified preparations of bacteriophage
      T4 resulted in significant reduction of tumour size, the effect being dose
      dependent. HAP1 was more effective than T4 and its activity was also dose
      dependent. Parallel experiments with non-purified bacteriophage lysates resulted
      in significant stimulation of tumour growth. CONCLUSION: These data suggest that
      purified bacteriophages may inhibit tumour growth, a phenomenon with potentially
      important clinical implications in oncology.

PMID- 15736443
TI  - Induction of apoptosis or necrosis in human endometrial carcinoma cells by 2
      methoxyestradiol.
AB  - BACKGROUND: We investigated the effects of 2methoxyestradiol (2-ME), an
      endogenous estrogenic metabolite, on human endometrial cancer HEC-1-A and RL-95-2
      cell lines. MATERIALS AND METHODS: After exposure of HEC-1-A and RL-95-2 cells to
      2-ME, the morphological changes were evaluated by acridine orange staining and
      transmission electron microscopy. Cell cycle progress, apoptosis and necrosis
      were assessed by flow cytometry, DNA fragmentation and Western blot. RESULTS: 2
      ME inhibited cell growth by blocking the S- and G2/M-phase in both cell lines, by
      inducing apoptosis in HEC-1-A cells and by causing necrosis in RL-95-2 cells.
      Apoptosis, on HEC-1-A cells, was accompanied by an increased expression of iNOS
      and STAT1. This apoptotic effect was prevented by the iNOS inhibitor 1400W and
      eliminated by the caspase inhibitor Z-VAD-FMK. Necrosis, on RL-95-2 cells, was
      due to a severe disruption of the mitochondrial membrane potential. 2-ME had no
      significant effect on normal human endometrial cells. CONCLUSION: The data
      suggest that 2-ME has an antitumor effect on human endometrial carcinoma cells
      (HEC-1-A and RL-95-2) and may contribute as a new therapeutic agent for
      endometrial cancer patients.

PMID- 15736445
TI  - Early effects of transplatin on oncogene activation in vivo.
AB  - The aim of the study was to investigate the early effect of Transplatin (the
      stereo-isomer of Cisplatin) on oncogenes in inbred CBA/Ca mice. Cisplatin is
      commonly used for the treatment of squamous cell carcinomas of the head and neck.
      Cisplatin has a strong oncogene activation effect compared to the structural
      analogue Transplatin. Body weight equivalent amounts of a human dose of
      Transplatin were administered intra-peritoneally to 6- to 8-week-old, inbred,
      female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was
      isolated from the target organs and the expressions of c-myc, Ha-ras and p53
      genes were examined. Investigation of early changes showed no significant
      overexpression compared to Cisplatin, which had a significant effect on oncogene
      expression in the "short-term" in vivo test system.

PMID- 15736446
TI  - Identification of calretinin and the alternatively spliced form calretinin-22k in
      primary pleural mesotheliomas and in their metastases.
AB  - BACKGROUND: Antibodies against calretinin represent an established, powerful and
      reliable immunohistochemical marker in the differential diagnosis between
      mesothelioma and adenocarcinomas. However, in studies published so far, the exact
      molecular identity of the immunoreactive protein(s) detected in mesothelioma
      sections has not yet been determined. MATERIALS AND METHODS: Tissue biopsies from
      ten mesothelioma samples, primary and metastatic, were analyzed by Western blot
      analysis and reverse transcriptase-polymerase chain reaction (RT-PCR), in
      addition to immunohistochemical staining. RESULTS: Besides the selective positive
      immunoreaction in all 10 samples, calretinin was identified by Western blot
      analysis and by identification of its mRNA by RT-PCR. In addition, we identified
      the alternatively spliced form calretinin-22k and the corresponding mRNA,
      previously detected only in neoplastic cells in colon carcinomas and derived cell
      lines. CONCLUSION: Our findings demonstrate that the immunoreactivity observed in
      the mesotheliomas and their metastases investigated in this report is due to the
      concomitant presence of calretinin and the alternatively spliced form calretinin
      22k.

PMID- 15736448
TI  - Vitamin B2 (riboflavin) and a mixture of vitamin B2 and C affects MMC efficiency
      in aerated media under irradiation.
AB  - Vitamin B2 (Riboflavin) acts as a strong radiation protecting agent in
      Escherichia coli bacteria (AB1157) in aerated media. This ability is reinforced
      by the addition of vitamin C. Under the influence of gamma-radiation, vitamin B2
      completely suppresses the cytostatic activity of mitomycin C (MMC). In the
      presence of both vitamins, B2 and C, MMC is converted from an efficient
      cytostatic to a rather strong radiation protecting agent. This effect opens a new
      pathway for specific protection of normal mammalian cells (with a high O2
      content) under treatment with ionizing radiation.

PMID- 15736449
TI  - Targeting against epidermal growth factor receptors. Cellular processing of
      astatinated EGF after binding to cultured carcinoma cells.
AB  - BACKGROUND: The alpha-emitting nuclide 211At is of great interest for
      radionuclide therapy when coupled to a tumor-targeting biomolecule, e.g.
      epidermal growth factor (EGF) the receptors of which are overexpressed in many
      malignancies. However, almost no information concerning the cellular processing
      of astatinated targeting agents is available. MATERIALS AND METHODS: We
      indirectly astatinated EGF ([211At]-benzoate-EGF) and studied its cellular
      processing in A-431 carcinoma cells in comparison with data concerning [125I]
      benzoate-EGF. RESULTS: The biological half-life of astatine (3.5 h) was longer
      than the half-life of the iodine label (1.5 h). The increase of the half-life was
      due to longer retention of the internalised astatine radioactivity. The maximum
      accumulation for the astatine label occurred later (4-6h) than that for the
      iodine label (2-4h), indicating a slower excretion of astatine that was confirmed
      in experiment with 211At/1251-benzoate-EGF. CONCLUSION: The long retention of
      astatine might be advantageous for radionuclide therapy.

PMID- 15736447
TI  - Histone deacetylase inhibitors enhance retinoid response in human breast cancer
      cell lines.
AB  - Solid tumors develop resistance to retinoids during carcinogenesis. One of the
      strategies to overcome this resistance may include the combination of these
      molecules with other differentiating, cytotoxic or chromatin-remodelling agents.
      We analysed the anti-proliferative activity of two histone-deacetylase inhibitors
      (HDACIs), Trichostatin A (TSA) and sodium phenylbutyrate (PB), alone or combined
      with retinoids, all-trans retinoic acid (ATRA) and Ro 41-5253, on two human
      breast cancer cell lines: the hormone-dependent MCF-7 and the hormone-independent
      MDA-MB-231. These lines responded differently to retinoids: MCF-7 were sensitive,
      whilst MDA-MB-231 were rather resistant. When the retinoids were combined with
      HDACIs, these molecules potentiated the retinoid activity on growth inhibition,
      especially for the association Ro 41-5253 and TSA. By FACS analysis, we observed
      that the anti-proliferative effects were only partially due to pro-apopotic
      mechanisms, suggesting a cell-cycle block. The efficacy of the retinoids/HDACIs
      combinations could represent a new strategy in breast cancer chemotherapy,
      allowing inhibition of both ER + and ER- cell populations.

PMID- 15736450
TI  - Intermediate stage Hodgkin's disease: preliminary results on 210 patients treated
      with four ABVD chemotherapy cycles plus extended versus involved field
      radiotherapy.
AB  - BACKGROUND: To improve long-term survival by reducing toxicity in intermediate
      stage Hodgkin's disease patients, we compared the effects of involved field (IF)
      versus extended field (EF) irradiation administered after four cycles of ABVD
      regimen. MATERIALS AND METHODS: Two hundred and ten Hodgkin's disease patients,
      at clinical stage II with risk factors and III without risk factors, were
      enrolled in the randomized study HD94. After four courses of ABVD regimen,
      patients who achieved complete remission (CR) or partial remission (PR) were
      randomly assigned to the IF or EF arm. The Kaplan-Meier method was adopted to
      estimate overall survival (OS) and relapse-free survival (RFS). RESULTS: After a
      median follow-up of 78 months (range 13-111 months), OS was 98% and 96%,
      respectively, in the EF and IF arms; RFS was 94% and 91%, respectively, in the EF
      and IF arms. CONCLUSION: We confirm the efficacy of four cycles of ABVD regimen,
      with suitable dose intensity, and radiotherapy as consolidation therapy, in
      intermediate stage Hodgkin's disease patients (CR = 99.5% and OS = 95%). We also
      found that involved field radiotherapy results were as effective as extended
      field, without acute toxicity.

PMID- 15736451
TI  - Elevated serum beta-defensins concentrations in patients with lung cancer.
AB  - BACKGROUND: Beta-defensins (HBDs) are expressed in lung epithelial cells and act
      as antimicrobial agents. Most lung cancers that originate from pulmonary
      epithelial cells may produce HBDs. MATERIALS AND METHODS: We measured serum HBD-1
      and HBD-2 levels in healthy subjects (HS), patients with lung cancer and patients
      with pneumonia by radioimmunoassay. RESULTS: Serum HBD-1 levels were higher in
      patients with lung cancer than HS and patients with pneumonia. Serum HBD-2 levels
      were higher in patients with lung cancer than HS. When cut-off values for
      positive HBD-1 were set at mean + 2SD of HS, the sensitivity and specificity of
      HBD-1 for the whole group of patients with lung cancer were 76.4 and 94.0%,
      respectively, and the proportion of patients with HBD-1-positive lung cancer and
      clinical stage I was 69.2%. CONCLUSION: Serum HBDs levels were high in patients
      with lung cancer and the serum HBD-1 level could be used as an auxiliary
      diagnostic tool for lung cancer.

PMID- 15736452
TI  - Comparison of Epstein-Barr virus DNA level in plasma, peripheral blood cell and
      tumor tissue in nasopharyngeal carcinoma.
AB  - BACKGROUND: The plasma Epstein-Barr virus DNA (EBV-DNA) level has been found to
      be an indicator for staging and prognosis of nasopharyngeal carcinoma (NPC).
      MATERIALS AND METHODS: The EBV-DNA level in plasma, peripheral blood cells (PBC)
      and neoplastic tissues was quantitatively analyzed and potential associations
      with clinical parameters of NPC were investigated. RESULTS: The plasma EBV-DNA
      detecting rate and level in NPC (92%, 82,500 copies/ml) was significantly higher
      than that in NPC after treatment (19%, 0 copy/ml) and in controls (12%, 0
      copy/ml) (p < 0.001); while there was no significance of the PBC EBV-DNA
      detecting rate and EBV-DNA load in NPC before (24%, 0 copy/actin) and after
      treatment (14%, 0 copy/actin), and in controls (16%, 0 copy/actin). The plasma
      EBV-DNA level was not correlated to the PBC EBV-DNA load in NPC before (p = 0.92)
      and after treatment (p = 0.267), and in controls (p = 0.735). The EBV-DNA level
      in NPC tumor (27.8 copies/actin) was significantly higher than that in
      nasopharyngitis and was positively correlated to the ratio of EBER1-positive
      cells on the NPC section (p = 0.001). The plasma EBV-DNA level was significantly
      increased in TNM stages I, II, III and IV NPC, whereas there was no significant
      difference of PBC EBV-DNA load in different stage NPC. CONCLUSION: Our results
      indicate that plasma EBV-DNA is a more sensitive and reliable biomarker than PBC
      EBV-DNA for diagnosis, staging and therapeutic effect evaluation at a molecular
      level in NPC clinical practice. Plasma EBV-DNA may derive from the cancer cells
      and PBC EBV-DNA from circulating mononuclear cells in NPC patients.

PMID- 15736453
TI  - Color coding cancer cells with fluorescent proteins to visualize in vivo cellular
      interaction in metastatic colonies.
AB  - We report here in vivo visualization of cancer cell interaction using stable
      sublines of green fluorescent protein (GFP)- and red fluorescent protein (RFP)
      expressing HT-1080 human fibrosarcoma cells. These color-coded fibrosarcoma cell
      lines show similar cell proliferation and lung metastasis potential. The color
      coded cells were mixed at a ratio of 1:1 and were injected into the tail vein of
      severe combined immunodeficient (SCID) mice. The resulting experimental lung
      metastases were simultaneously imaged and their ratio was determined by color
      pixel analysis. Fluorescence color coding of cancer cells enables visualization
      of the interaction of cancer cells and can be used to distinguish cancer cells of
      any genotype or phenotype.

PMID- 15736454
TI  - Bronchoscopic treatment with argon plasma coagulation for recurrent typical
      carcinoids: report of a case.
AB  - Carcinoid tumors are recognized as a low-grade malignancy. Recurrence of
      bronchopulmonary typical carcinoids is extremely rare. We herein report a case of
      recurrent multiple intraluminal bronchial typical carcinoids that were
      successfully removed using argon plasma coagulation by bronchoscopic approach. A
      48-year-old man, who had undergone resection of a pulmonary typical carcinoid 8
      years previously, suffered from a productive cough and hemosputum for a month.
      Bronchoscopic examination revealed multiple intraluminal bronchial polypoid
      tumors. Based on histopathological findings, we diagnosed recurrence of typical
      carcinoids. The patient underwent argon plasma coagulation (APC) treatment by
      bronchoscopic approach several times. APC treatment is considered to be a safer
      method than conventional bronchoscopic treatment with neodymium-yttrium aluminum
      garnet (Nd-YAG) laser or electrocautery. After a series of treatments, his
      symptoms completely improved and no recurrence was found during 10 months of
      follow-up.

PMID- 15736455
TI  - Correlation between the histological grade of chondrosarcoma and the expression
      of MMPs, ADAMTSs and TIMPs.
AB  - BACKGROUND: The malignant degree of human chondrosarcoma can be difficult to
      determine using only histological findings. We, therefore, assessed the
      expression of matrix metalloproteinases (MMPs), a disintegrin and
      metalloproteinase (ADAM) with thrombospondin motifs (ADAMTSs) and tissue
      inhibitor of metalloproteinases (TIMPs) in chondrosarcoma and ascertained the
      relationships to histological degree of malignancy and prognosis. MATERIALS AND
      METHODS: In 28 chondrosarcoma cases, immunostaining was performed using
      antibodies against MMP 2, 3, 7, 9, 13, ADAMTS 4, 5 and TIMP 1, 2, 3. RESULTS: The
      chondrosarcoma were classified into groups of 7, 15 and 6 cases based on
      histologically malignant grade I, II and III, respectively. All target proteins
      were expressed in chondrosarcoma. Positive correlations (p < 0.05) existed
      between immunostaining scores and histological grades for all proteins except MMP
      9, with strong correlations (p < 0.01) for MMPs 2, 3 and 13, both ADAMTSs and all
      3 TIMPs. No correlation existed between prognosis and immunostaining scores.
      CONCLUSION: These target proteins could, thus, indicate the degree of malignancy
      in human chondrosarcoma.

PMID- 15736456
TI  - Imbalance in expression levels of insulin-like growth factor 2 and H19
      transcripts linked to progression of hepatocellular carcinoma.
AB  - BACKGROUND: The imprinted genes insulin-like growth factor 2 (IGF2) and H19 play
      important roles in various malignancies including hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: We used DNA microarray and patient follow-up data to
      examine the relationship between expression of IGF2 and H19 and HCC. RESULTS: We
      found that imbalances in levels of IGF2 and H19 transcripts were correlated with
      advanced tumor stage and poor outcome in HCC patients. CONCLUSION: In addition to
      their known epigenetic or genetic abnormality in malignancies, these findings
      suggest that altered transcription of these two imprinted genes contributes to
      progression of HCC.

PMID- 15736457
TI  - The effectiveness of planned esophagectomy after neoadjuvant chemoradiotherapy
      for advanced esophageal carcinomas.
AB  - BACKGROUND: The best treatment option for patients with locally advanced
      esophageal carcinoma has not yet been determined, especially because the benefits
      of esophagectomy after neoadjuvant chemoradiotherapy are still controversial. We
      report the results of a retrospective cohort comparison of definitive
      chemoradiotherapy without surgery (CRT) versus neoadjuvant chemoradiotherapy
      followed by planned surgery (CRTS) in patients with advanced esophageal squamous
      cell carcinoma (SCC). MATERIALS AND METHODS: Between January 1991 and December
      2002, 67 patients were enrolled in this study. Fifty of the 67 patients were
      considered to have inoperable tumors due to distant organ metastasis, distant
      lymph node metastasis, severe organ dysfunction or rejection of surgery by the
      patient and received CRT, while the remaining 17 patients were treated with CRTS.
      The clinical responses of the primary tumors were evaluated. RESULTS: In the 50
      CRT patients, the one- and 2-year survival rates were 33.8% and 20.2%,
      respectively, and the median survival time (MST) was 13.5 months. In the 17 CRTS
      patients, the response rate (CR + PR) was 76.5%, and the pathological complete
      response (pCR) rate was 29.4%. Their one- and 2-year survival rates were 61.6%
      and 35.9%, respectively, and the MST was 24.4 months. The survival rates of the
      CRT patients were lower than those of the CRTS patients (p = 0.1288). When the 12
      patients with distant organ metastases were removed from the CRT group, the one-
      and 2-year survival rates of the remaining 38 patients were 36.5% and 24.1%,
      respectively, and the MST was 14.7 months. The survival rates of these 38 CRT
      patients without distant organ metastases were similar to those of the 12 CRTS
      patients in the pathological partial response (pPR) group (p = 0.6279).
      CONCLUSION: This retrospective cohort comparison of CRT versus CRTS demonstrated
      that there may not be any survival benefit from the addition of surgery in the
      pPR group for advanced esophageal carcinomas. For patients with a poor response
      to neoadjuvant chemoradiotherapy, we suggest that the addition of
      chemoradiotherapy, instead of planned esophagectomy, may show a similar survival
      rate to definitive CRT. Thus, a large series of a randomized control study will
      be required to confirm the benefit of surgery after chemoradiotherapy.

PMID- 15736458
TI  - MRI diagnosis of mesorectal lymph node metastasis in patients with rectal
      carcinoma. what is the optimal criterion?
AB  - BACKGROUND: Preoperative diagnosis of lymph node metastasis is often difficult. A
      number of different criteria have been advocated in the literature, however, an
      optimal criterion has not yet been determined in patients with rectal carcinoma.
      PATIENTS AND METHODS: Fifty-one patients, undergoing radical surgery with total
      mesorectal excision, were examined with reference to regional lymph node status.
      MRI and pathological findings were compared, and an optimal preoperative
      criterion was clarified by receiver operating characteristic (ROC) analysis.
      RESULTS: Among size, shape and internal structure criteria, size was a
      significant factor for diagnosing metastatic lymph node on MRI. ROC analysis
      showed that a criterion of 6-mm or larger in the longitudinal axis was the most
      reliable in differentiating metastatic and non-metastatic lymph nodes, with
      overall accuracy of 78%. CONCLUSION: A 6-mm longitudinal diameter criterion is
      thought to be most optimal in the evaluation of mesorectal lymph node status in
      patients with rectal carcinoma.

PMID- 15736459
TI  - Application of PET and PEt/CT imaging for cancer screening.
AB  - The aim of this study was to evaluate the potential application of 18
      fluorodeoxyglucose positron emission tomography (FDG PET) and PET/CT for cancer
      screening in asymptomatic individuals. The subjects consisted of 3631 physical
      check-up examinees (1947 men, 1684 women; mean age +/- SD, 52.1 +/- 8.2 y) with
      non-specific medical histories. Whole-body FDG PET (or PET/CT), ultrasound and
      tumor markers were performed on all patients. Focal hypermetabolic areas with
      intensities equal to or exceeding the level of FDG uptake in the brain were
      considered abnormal and interpreted as neoplasia. Follow-up periods were longer
      than one year. Among the 3631 FDG PET (including 1687 PET/CT), ultrasound and
      tumor markers examinations, malignant tumors were discovered in 47 examinees
      (1.29%). PET findings were true-positive in 38 of the 47 cancers (80.9%). In
      addition, 32 of the 47 cancers were screened with the PET/CT scan. PET detected
      cancer lesions in 28 of the 32 examinees. However, the CT detected cancer lesions
      in only 15 out of 32 examinees. The sensitivity of FDG PET in the detection of a
      wide variety of cancers is high. Most cancer can be detected with FDG PET at a
      resectable stage. CT of the PET/CT for localization and characteristics of the
      lesion showed an increased specificity of the PET scan. The use of ultrasound and
      tumor markers may complement the PET scan in cancer screening for hepatic and
      urologic neoplasms.

PMID- 15736461
TI  - Masaoka staging is of prognostic relevance in type B3 / C thymomas.
AB  - BACKGROUND: The purpose of this study was to correlate the Ki67 labelling index
      (LI) with the Masaoka classification and the new WHO-classification in type B3 /
      C thymomas. PATIENTS AND METHODS: Fourteen patients with type B3 / C thymomas
      were evaluated, and archived specimens were histologically reclassified according
      to Masaoka staging, the new WHO classification and the Ki-67 LI in a
      retrospective analysis. RESULTS: Four patients presented with Masaoka stage II
      disease (all WHO-type B3), 1 patient had stage III (WHO-type C), 6 stage IVa (3
      WHO-type B3 and 3 WHO-type C), and another 3 patients stage IVb (all WHO-type C).
      The statistical analysis revealed a significant correlation between Masaoka
      staging and Ki-67 LI (II, III vs. IV; p = 0.007). As well, WHO-classification
      correlated significantly with Ki-67 LI (B3 vs. C; p = 0.015). Masaoka staging
      (II, III vs. IV) correlated significantly with survival status (p = 0.0237) in
      patients with type B3 / C thymoma whereas WHO-classification did not (p =
      0.3266). Between survivors and non-survivors there was no statistically
      significant correlation concerning Ki-67 LI (p = 0.075). CONCLUSION: Our study
      indicated that the Masaoka staging system is of prognostic relevance in type B3 /
      C thymomas.

PMID- 15736460
TI  - Sedation in gynaecologic oncology day surgery.
AB  - Gynaecologic oncology day surgery deals primarily with the diagnosis of
      endometrial, cervical, vulvar and vaginal tumors. Conscious sedation is an
      important technique used in gynaecologic oncology day surgery. It is often
      associated with regional anaesthesia. The goals of conscious sedation are to
      provide effective pain control with complete safety, reduction of the recovery
      time, of the infection risk and cost. Since the consequences of the
      immunosuppressive effects of the opiates and the surgical stress could lead to an
      increased susceptibility to post-operative infections and a possible lack of
      immunological defence in the cancer patients, we investigated the possibility of
      eliminating the administration of opiates during minor operations in gynaecologic
      oncology day surgery. In this study, 400 patients, aged between 35 and 77 years,
      underwent surgery using sedation at the day hospital annexed to the Gynaecology
      and Obstetrics Department of the 2nd University of Naples, Italy. The patients
      were randomized into two equal study groups, according to a computer-generated
      randomised list. All patients were seen by the consultant anaesthetist three days
      before surgery. In all cases, during surgery, we monitored the main vital
      parameters such as ECG, HR and RR, BT, BP and SO. The drugs commonly used were:
      opioids, hypnotics and benzodiazepines, associated or not, with local
      anaesthetics. By using these drugs, pain and anxiety were reduced, sedation and
      amnesia were accomplished. In our experience, conscious sedation seems to be the
      best choice in gynaecologic oncology day surgery because it presents low
      toxicity, is short acting and readily reversible, has a low cost and, finally,
      because it is more comfortable for the patients. Moreover, it is possible to
      eliminate the administration of opiates during conscious sedation for less
      invasive surgical procedures.

PMID- 15736462
TI  - Clinical response following adjuvant Temozolomide in a patient with primary
      cerebral lymphoma.
AB  - A 69-year-old female patient was treated for primary CNS-lymphoma (PCNSL)
      starting from August 2002. As her general condition allowed no high-dose
      methotrexate (MTX) therapy, radiotherapy was administered as a first-line
      treatment. CSF involvement could be managed by intrathecal Ara-C. Her general
      condition and cognitive status stabilized, but did not improve for 3 months.
      Therefore, oral chemotherapy with Temozolomide 200 mg/m2 was initiated. After two
      courses, which were tolerated without any problems, the patient's Karnofsky
      performance index had improved from 40% to 50%, the Mini-Mental Status rose from
      16 to 27/30. The CSF-cell count was elevated again to 23 cells/l without signs of
      meningeal relapse. Unfortunately, the patient died unexpectedly from suspected
      pulmonary embolism. We conclude that adjuvant Temozolomide chemotherapy can
      improve the general condition and cognition in patients with PCNSL even when the
      general condition is poor. Long-term effects and neurotoxicity remain to be
      analysed in prospective trials, as well as the efficacy in leptomeningeal
      disease.

PMID- 15736463
TI  - Molecular markers for human colon cancer in stool and blood identified by RT-PCR.
AB  - There is a need for sensitive and specific diagnostic and prognostic molecular
      markers which can monitor early patterns of gene expression in non-invasive
      exfoliated colonocytes shed in the stool, and aggression in carcinoma cells in
      blood of resected colorectal cancer patients. RNA-based detection methods are
      more comprehensive than either DNA- or protein-based methods. By routinely and
      systematically being able to perform quantitative gene expression studies on non
      invasive samples using carefully selected tumor-specific colon cancer genes, we
      can quantitatively and accurately monitor changes at various stages in the
      neoplastic process, allowing for surgical and/or other therapies, and thus,
      decrease mortality from colorectal cancer.

PMID- 15736464
TI  - Concurrent chemoradiotherapy with cisplatin and docetaxel for advanced head and
      neck cancer. A phase I study.
AB  - BACKGROUND: This phase I study of weekly low-dose administration of cisplatin
      (CDDP) and docetaxel (DOC) combined with concurrent conventionally fractionated
      radiotherapy was designed for locoregionally advanced head and neck cancer.
      PATIENTS AND METHODS: Twelve patients were treated at varying levels of DOC
      (level 1: 5 mg/m2/week, level 2: 7.5 mg/m2/week, level 3: 10 mg/m2/week) with
      CDDP constant at 20 mg/m2/week in four cohorts of three patients. Radiation was
      given at 1.8-2.0 Gy/fraction to a total dose of 60-70.2 Gy. RESULTS:
      Hematological toxicities, except lymphocytopenia, were minimal. Mucosal
      toxicities, especially grade 3 mucositis, were common. Dose-limiting toxicity was
      grade 3 pain, although level 3 did not reach a maximum tolerated dose. No grade 4
      toxicities were observed. Complete response rate ranged from 33% to 67% in the
      various dose levels. CONCLUSION: This concurrent chemoradiotherapy seems to be a
      promising treatment modality, in which level 3 is the recommended dose for a
      phase II study.

PMID- 15736465
TI  - Cytogenetic data as a prognostic factor in multiple myeloma patients: involvement
      of 1p12 region an adverse prognostic factor.
AB  - BACKGROUND: Multiple myeloma (MM) is charecterized by great clinical
      heterogeneity. Among known prognostic factors the cytogenetic abnormalities are
      thought to be of major importance. The aim of this study was to correlate certain
      chromosomal abnormalities with immunoglobulin isotype and survival in MM
      patients. PATIENTS AND METHODS: Forty-nine Greek MM patients, homogeneously
      treated with conventional-dose chemotherapy, were cytogenetically studied by
      direct culture of bone marrow cells and G-banding technique. RESULTS: Twenty-four
      patients had a normal karyotype while the remaining 25 patients presented
      numerical and structural abnormalities. Recurrent structural abnormalities were
      observed. Translocations involving the 14q32 region were observed in 8 cases,
      while 6 cases exhibited a del(1)(p12). We confirmed the negative impact of
      chromosomal abnormalities on the overall survival of MM patients and we also
      showed that t(11;14) had a worse impact on disease outcome as compared to
      t(14q32) with an unidentified partner chromosome. The presence of del(1) (p12)
      significantly worsened the prognosis in MM patients. No correlations existed
      between the association of immunoglobulin isotype with survival or certain
      chromosomal changes. CONCLUSION: Further studies are indicated at the molecular
      level to clarify the exact role and the prognostic value of 1p12 involvement in
      MM patients.

PMID- 15736466
TI  - Cathepsin B, plasminogenactivator-inhibitor (PAI-1) and plasminogenactivator
      receptor (uPAR) are prognostic factors for patients with non-small cell lung
      cancer.
AB  - To evaluate the possible role of cysteine proteases and serine proteases, as well
      as their respective inhibitors and receptors, as new prognostic factors in NSCLC,
      we examined, for the first time, 10 biological parameters related to three
      proteolytic systems within a homogeneous collective of 147 cases of NSCLC.
      Activities (cath B(AT), cath B(A7.5)) and protein levels of cath B(C), cath L(C),
      uPA, PAI-1, uPAR [measured by three different assays uPAR (ADI), uPAR (HD13),
      uPAR (IIIF10)] and TF were measured in homogenates of lung tumour tissue and
      corresponding non-malignant lung parenchyma. Total cath B activity (cath B(AT))
      and enzymatic activity of the fraction of cath B, which is stable and active at
      pH 7.5 (cath B(A7.5)), were determined by a fluorogenic assay using synthetic
      substrate Z-Arg-Arg-AMC. The concentrations of cath B(C), cath L(C), uPA, PAI-1,
      uPAR and TF were determined by ELISAs. uPAR was determined using three different
      ELISA formats. The median levels of cath B(AT) (5.1-fold), cath B(A7.5) (2.5
      fold), cath B(C), (8.5-fold), cath L(C) (6.6-fold), uPA (6.5-fold), PAI-1 (4.2
      fold), uPAR (ADI) (2.2-fold), uPAR (HD13) (4.0-fold) and uPAR (IIIF10) (2.6-fold)
      were higher in tumour tissue compared to the lung parenchyma. Cath B(AT), cath
      B(A7.5) and cath B(C) in primary tumours correlated with lymph node metastases.
      Regarding histologies, the concentration of PAI-1 seems to be associated with the
      histological cell types of NSCLC. We found the highest values of PAI-1 in large
      cell carcinoma > SCC, AC > carcinoid and lowest values in metastases of primary
      tumours of other organs. Only PAI-1 was significantly increased in poorly
      differentiated cells (G3) compared to well- and moderately- differentiated cells
      (G1/G2). PAI-1 significantly correlated with cath B(AT) and cath B(A7.5) with
      uPAR (ADI), uPAR (HD13), uPAR (IIIF10) with uPA, and only weakly with TF, but not
      with cath B(C) and cath L(C). Significant correlations with overall survival in
      the total population of NSCLC patients were observed in univariate analysis for
      cath B(AT), cath B(C), PAI-1, uPAR (ADI), uPAR (HD13), and uPAR (IIIF10). Cath
      L(C) was not significantly associated with poor prognosis. Regarding the
      histological tumour type, only in patients with squamous cell carcinomas did cath
      B(A7.5) and PAI-1 remain significant prognostic factors. In multivariate survival
      analysis only two proteolytic factors, PAI-1 and uPAR (III101F), stayed
      significant. In conclusion, among 10 biological parameters evaluated within the
      same cohort of patients, only PAI-1, uPAR (ADI), uPAR (HD13), uPAR (IIIF10), cath
      B(AT) and cath B(C) are prognostic factors for overall survival of NSCLC
      patients. Moreover, PAI-1 and uPAR (IIIF10) add independent prognostic
      information with regard to established clinical and histomorphological factors in
      NSCLC.

PMID- 15736467
TI  - Role of endoscopic clipping for determining the resection line for tumors located
      in the middle or upper corpus of the stomach: experience with 100 gastrectomies
      for early gastric cancer.
AB  - BACKGROUND: The efficacy and limitations of preoperative endoscopic clipping for
      determining the resection line in patients with early gastric cancer remain
      unclear. MATERIALS AND METHODS: Subjects comprised 100 patients with early
      gastric cancer (33 females, 67 males; mean age, 60.5 years; range, 33-84 years)
      who underwent pre-operative endoscopic clipping for lesions located in the middle
      or upper corpus of the stomach. The results of endoscopic clipping for a
      selection of appropriate surgical procedures were investigated. RESULTS: Distal
      gastrectomy was performed in 94 patients, the mean length between the lesion and
      proximal surgical margin of the resected stomach being 28.9 +/- 18.0 mm (mean +/-
      SD). The surgical margin was eventually free of tumor in all patients. In 5
      patients, clips were considered to be placed inadequately, and all 5 tumors were
      macroscopically depressed or flat and > 40 mm in size. CONCLUSION: Pre-operative
      endoscopic clipping represents a safe and reliable procedure to determine the
      resection line for tumors located in the middle or upper corpus of the stomach
      for treatment of early gastric cancer. During surgical resection, frozen section
      examination of the proximal cut end is recommended for patients with tumors that
      are macroscopically depressed or flat and > 40 mm in size, or that display a
      macroscopically unclear proximal margin.

PMID- 15736469
TI  - Correlation of diffusion-weighted MR imaging with cellularity of renal tumours.
AB  - BACKGROUND: Diffusion is a physical process based on the random movement of water
      molecules known as Brownian movement. Diffusion-weighted imaging (DWI) is a
      magnetic resonance (MR) technique that provides information about the biophysical
      properties of tissues such cell organization and density, microstructure and
      microcirculation. MATERIALS AND METHODS: Twenty healthy volunteers and 18
      patients with renal tumor were enrolled in our study. The DWI was obtained before
      contrast media injection with a single-shot SE EPI Inversion Recovery (IR)
      sequence. The tumor cellularity of each resected lesion was evaluated. RESULTS:
      The mean apparent diffusion coefficient (ADC) value of renal tumors was
      significantly lower than the mean ADC value of normal renal parenchyma. In our
      series, the mean ADC value of renal tumors did not significantly correlate with
      tumor cellularity, but correlated with histological architecture. CONCLUSION:
      These preliminary results indicate the utility of DWI in the acquisition of
      tissue characterization data of renal masses using a minimal acquisition time (17
      sec).

PMID- 15736468
TI  - Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung
      carcinoma.
AB  - BACKGROUND: We explored the expression of Fatty Acid Synthase (FAS) in lung
      carcinomas and its association with clinico-pathological features and prognosis.
      FAS is a recently discovered molecule involved in the energy supply of normal
      cells. FAS is also overexpressed in neoplastic tissues because of their increased
      necessity for energy. PATIENTS AND METHODS: One hundred and six patients with non
      small cell lung carcinoma were followed-up for an average period of 5 years. FAS
      expression was detected immunohistochemically. RESULTS: FAS staining was observed
      in 61 out of 106 cases (57.54%). Statistical analysis revealed that FAS had an
      overall low prognostic value (p = 0.14), while FAS-negative expression in stage I
      patients showed a trend for better survival (p = 0.10). PTNM stage (p < 0.0001)
      was the only significant prognostic marker for overall survival. CONCLUSION: FAS
      is a reliable marker of low-stage clinically aggressive lung carcinomas. The
      determination of FAS expression in lung carcinomas may stratify patients and
      determine therapeutic approaches for their care.

PMID- 15736470
TI  - Complexed prostate-specific antigen for the detection of prostate cancer.
AB  - BACKGROUND: The description of a new method for the measurement of complexed
      prostate-specific antigen (cPSA) offers a new approach to the diagnosis of
      prostate cancer. PATIENTS AND METHODS: We measured PSA (Hybritech and Bayer),
      free PSA (Hybritech) and complexed PSA (Bayer) in 72 patients with prostate
      cancer and 128 with benign prostate hyperplasia. RESULTS AND CONCLUSION: We found
      an increase of sensitivity using 25 and 7 ng/mL as cut-offs for cPSA in relation
      to total PSA using as cut-offs 4 and 10 ng/mL (96 and 36% vs. 92 and 35.5%).
      Similar differences were found for specificity (78% and 31% for cPSA vs. 73% and
      29% for total PSA). Therefore, we defined a gray zone for patients with cPSA
      between 2.5 and 7 ng/mL for which the measurement of the free/complexed PSA ratio
      saves an important number of negative biopsies maintaining a higher sensitivity.

PMID- 15736471
TI  - Paneth cell adenoma of the ileum.
AB  - A Paneth cell adenoma of the ileum was recently found in a 47-year-old male with
      familial adenomatous polyposis (FAP). The patient had years previously been
      subjected to a total proctocolectomy. Following surgery, endoscopical biopsies
      were obtained from the duodenum (10 biopsies) in four instances and from the
      ileal pouch (6 biopsies) in three. All biopsies were taken between 1988 and 2003.
      Hematoxylin and eosin (H&E) sections from all those 16 biopsies were reviewed. In
      one biopsy from the ileal pouch, a tubular adenoma carrying 92% dysplastic Paneth
      cells was found. Paneth cells were more easily singled out when H&E sections were
      observed in a fluorescent microscope than when using conventional transmitted
      light, or lysozyme immunostain. Despite a wide distribution of Paneth cells in
      mucosas with intestinal metaplasia (e.g. Barrett's esophagus and gastric
      intestinal metaplasia), in the normal small intestine and in the large intestine
      with chronic inflammatory diseases only a few Paneth cell neoplasias have been
      reported in the GI tract. The cause of the apparent natural resistance of these
      specialized cells provided with anti-microbial and growth factors to undergo
      neoplastic transformation deserve further investigation. A review of the
      literature indicates that this is the first reported case of Paneth cell adenoma
      of the small intestine.

PMID- 15736472
TI  - Application of new ploidy-related parameters for the diagnosis of ovarian
      tumours.
AB  - Differential diagnostics of borderline ovarian tumours and ovarian carcinomas is
      generally based on morphological criteria, which are not always sufficient for
      final diagnosis. Therefore, we investigated the practical diagnostic application
      of the CAS200 image analyzer and new ploidy-related parameters in a series of 68
      borderline tumours and 42 low-grade carcinomas of the ovary. Highly significant
      differences between borderline and malignant lesions were found for the
      percentage of diploid cells (p = 0.0001), the percentage of aneuploid cells
      between 4c and 8c (p = 0.0001), the percentage of octaploid cells (p = 0.0001),
      as well as for the 5c exceeding rate (p = 0.0001). The difference concerning the
      ratio of tetraploid cells also reached the level of significance (p = 0.0320). We
      suggest that new ploidy-related parameters evaluated by the CAS200 image analyzer
      can be helpful in ovarian lesions with unclear morphology.

PMID- 15736473
TI  - High-dose tamoxifen treatment increases the incidence of multifocal tumor
      recurrences in glioblastoma patients.
AB  - BACKGROUND: Multifocal tumor recurrences in glioblastoma patients are described
      in 4% - 14% of cases. Two recent studies, treating newly diagnosed glioblastoma
      patients with continuous high-dose tamoxifen (TAM), reported an increased
      incidence of multifocal tumor recurrences in 45.5% and 33% of study patients.
      PATIENTS AND METHODS: Fifty newly diagnosed patients with glioblastoma were
      treated with 3 cycles of carboplatin, continuous high-dose TAM and radiotherapy.
      Tumor progression was determined on follow-up MRI studies at 3-month intervals
      and categorized as either local or multifocal. RESULTS: Multifocal tumor
      recurrence was found in 16 (33%) out of 49 study patients. Compared to tumors
      which remained local, multifocal tumor recurrences were characterized by a
      significantly longer median time to tumor progression (41 vs. 23 weeks, Breslow
      test: p = 0.0123). Multifocal tumor recurrences were mainly observed after an
      initial response to the study treatment (81%), whereas local regrowth was more
      often associated with initial treatment failure, i.e. progressive disease (64%).
      CONCLUSION: The association of the pattern of tumor recurrence with the type of
      response to TAM treatment suggests that acquired resistance to TAM might be an
      important contributing mechanism in the development of multifocal glioblastoma
      disease.

PMID- 15736474
TI  - Influence of tumor biological factors on tumor cell dissemination in primary
      breast cancer.
AB  - BACKGROUND: The presence of disseminated tumor cells in the bone marrow (BM) of
      breast cancer patients is associated with poor prognosis and may therefore be
      related to aggressive breast cancer as indicated by tumor biological and
      clinicopathological factors. The aim of this study was to identify those features
      of the primary tumor related to the presence of disseminated tumor cells in the
      BM. PATIENTS AND METHODS: Clinical data from 508 primary breast cancer patients
      were analyzed. Tumor biological features of the primary tumor including HER2,
      p53, Ki-67, bcl-2 and hormone receptor status, as well as clinicopathological
      factors including histology, menopausal status, lymph node status, tumor size and
      grade, were studied for their association with BM involvement by univariate and
      multivariate analysis. RESULTS: Two-hundred and two out of 508 (40%) primary
      breast cancer patients had disseminated tumor cells in the BM. p53 expression,
      hormone receptor status, HER2 and Ki-67 were significantly related to BM
      involvement. The multivariate analysis revealed that p53 expression (OR: 1.9, 95%
      CI: 1.2 - 3.0) followed by progesterone receptor status (OR: 1.5, 95% CI: 1.0 -
      2.2) were the only independent determinants for BM involvement. CONCLUSION: The
      presence of disseminated tumor cells in the BM was not influenced by tumor load
      as reflected by tumor size and lymph node involvement, whereas tumor biological
      factors were independently correlated to BM involvement. The results substantiate
      the important role of tumor biological factors of the primary tumor for tumor
      cell dissemination.

PMID- 15736475
TI  - A dose escalation study of leucovorin (LV) and 48-hour continuous infusion of 5
      fluorouracil in combination with cyclophosphamide and vinorelbine in pretreated
      patients with metastatic breast cancer.
AB  - PURPOSE: To determine the maximum tolerated doses (MTD) and dose-limiting
      toxicities (DLTs) of vinorelbine (VNR) with fixed doses of cyclophosphamide (CPM)
      and 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic breast cancer
      (MBC) pretreated with anthracyclines and taxanes. PATIENTS AND METHODS: Eighteen
      patients with MBC pretreated with anthracyclines and taxanes were enrolled. VNR
      was administered as a 10-min intravenous infusion (i.v.) on day 1 at escalated
      doses with CPM 300 mg/m2 i.v. bolus and LV 500 mg/m2 as a 2-hour i.v. infusion,
      followed by 5-FU 1500 mg/m2 as a 22-hour continuous infusion (c.i.) for two
      consecutive days. Treatment was repeated every two weeks. RESULTS: At the dose of
      VNR 22.5 mg/m2 without rhG-CSF and 25 mg/m2 with rhG-CSF support, the DLT had
      been reached. Grade 3 or 4 neutropenia occurred in six (33%) patients and in
      fourteen (27%) cycles with no episode of febrile neutropenia. One (5.5%) patient
      developed grade 4 thrombocytopenia. Grade 3 neurotoxicity occurred in two
      patients and grade 2 and 3 asthenia in five (28%). CONCLUSION: The recommended
      doses for phase II studies are 20 mg/m2 for VNR (22.5 mg/m2 with rhG-CSF support)
      and 300 mg/m2 for CPM on day 1, with 500 mg/m2 for LV and 1500 mg/m2 for 5-FU on
      days 1 and 2.

PMID- 15736476
TI  - Enhancement of the efficacy of weekly low-dose taxotere by the long acting anti
      prolactinemic drug cabergoline in pretreated metastatic breast cancer.
AB  - In view of its potential action as a growth factor, the evidence of abnormally
      high blood levels of prolactin (PRL) is associated with a poor prognosis in
      metastatic breast cancer. Moreover, metastatic breast cancer-related
      hyperprolactinemia has proven to counteract the efficacy of cancer chemotherapy.
      The negative influence of high blood levels of PRL on the efficacy of
      chemotherapy in metastatic breast cancer has been confirmed by previous
      preliminary studies, showing that the concomitant administration of the anti
      prolactinemic dopaminergic agent bromocriptine may enhance the therapeutic effect
      of chemotherapy. However, the clinical use of bromocriptine is limited by its
      short duration and gastrointestinal toxicity. Therefore, new anti-prolactinemic
      drugs, characterized by less toxicity and a longer duration of activity, such as
      Cabergoline (CBG), could be more appropriated to control PRL secretion in breast
      cancer. On this basis, a study was planned to evaluate the efficacy and
      tolerability of a concomitant administration of CBG with weekly low-dose Taxotere
      (TXT) in pretreated metastatic breast cancer under chemotherapy. The study group
      comprised 70 metastatic breast cancer patients (females), pretreated with at
      least one previous chemotherapeutic line containing anthracyclines, who were
      randomized to be treated with TXT alone or TXT plus CBG. TXT 25 mg/m2 was given
      i.v. at weekly intervals for at least 9 consecutive cycles. CBG was given orally
      at 0.5 mg once per week. Abnormally high pre-treatment levels of PRL were seen in
      24/70 (34%) patients, 11 of whom were treated with TXT plus CBG, whereas the
      other 13 received TXT alone. CBG induced a complete normalization of the PRL
      levels in all patients within the first two weeks of therapy, whereas no
      normalization of PRL occurred spontaneously in patients treated with chemotherapy
      alone. The objective tumor regression rate was significantly higher in patients
      concomitantly treated with CBG than in those who received chemotherapy alone
      (31/34 vs 13/36, p < 0.05), and this difference was particularly evident in
      patients with high PRL levels prior to therapy (6/11 vs 2/13). No CBG-related
      toxicity occurred. On the contrary, chemotherapy-induced asthenia was
      significantly lower in patients concomitantly treated with CBG (5/34 vs 11/36, p
      < 0.05). This study shows that the chemoneuroendocrine therapy of weekly low-dose
      TXT plus the anti-prolactinemic drug CBG is a new, effective and well-tolerated
      therapy for metastatic breast cancer. It may also be recommended in heavily
      pretreated patients or in those with poor clinical status.

PMID- 15736477
TI  - Cisplatin and vinorelbine remains a valid option for the front-line chemotherapy
      treatment of NSCLC.
AB  - BACKGROUND: This study was designed to confirm the activity of the
      cisplatin/vinorelbine (C/V) combination in non-small cell lung carcinoma (NSCLC).
      PATIENTS AND METHODS: Treatment consisted of vinorelbine, i.v. slow infusion of
      30 mg/m2 every week, and cisplatin, 120 mg/m2 on days 1 and 29 and then every 6
      weeks. Treatment was continued until completion of the 22-week treatment plan,
      disease progression, persistent toxicity, or patient refusal. RESULTS: Seventy
      five patients entered the study. The median age was 62 years; major cell types
      were adeno- (38), squamous (26) and large cell carcinomas (7). Nineteen patients
      received a suboptimal treatment with less than 6 courses of vinorelbine. The
      median courses of C/V were 3 (range 0-4) and 15 (range 0-22), respectively. For
      both drugs, the median dose-intensity was 75% of projected. Toxicity was
      generally acceptable, mainly hematological and never life-threatening. Thirty
      five patients responded, with 8 complete responses, for an overall response rate
      of 46.7%. The estimated median time to progression was 28 weeks (quartile range:
      13-46); the median survival 60 weeks (quartile rage: 17-108). CONCLUSION: The C/V
      combination is fairly well tolerated, decidedly active and associated with
      prolonged survivals.

PMID- 15736479
TI  - Imbalance of cell proliferation and apoptosis during progression of lung
      carcinomas.
AB  - To evaluate the relationship between cell proliferation and apoptosis during
      progression of lung carcinomas, immunohistochemistry for proliferating cell
      nuclear antigen (PCNA) and the in situ end labelling (TUNEL) method for
      identifying apoptotic bodies were performed on paraffin sections from 135 lung
      carcinomas. These results were correlated with the corresponding tumor volumes as
      a model of disease progression in lung tumors. We found that, with increasing
      tumor volume, the proliferation rate decreased significantly, whereas the
      apoptotic rate increased. There was no relationship between apoptotic and
      proliferative indices except in carcinomas with a tumor volume between 51 and 100
      cm3. These data suggest that progression of lung carcinomas, i.e. the increase in
      tumor volume, is accompanied by an increase in apoptosis rather than an increase
      in cell proliferation.

PMID- 15736478
TI  - Circulating vascular endothelial growth factor during the normal menstrual cycle.
AB  - BACKGROUND: The purpose of the study was to investigate whether cycle-related
      variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would
      increase the metastatic potential at specific times during the menstrual cycle.
      MATERIALS AND METHODS: VEGF levels in serum and whole blood were evaluated during
      the normal menstrual cycle in premenopausal women. Determination of the menstrual
      phase was based on hormonal measurements. RESULTS: A total of 46 samples were
      taken of six menstrual cycles. Serum VEGF was inversely related with progesterone
      levels (r = -0.6, p = 0.012). Throughout the menstrual cycle the serum VEGF
      decreased indicating that the lowest VEGF level occurs during the secretory
      phase, which is compatible with the inverse relationship between serum
      progesterone and VEGF. CONCLUSION: These findings, however, do not suggest that
      individual VEGF levels can direct the optimal timing of surgical intervention in
      breast cancer.

PMID- 15736480
TI  - Matrix metalloproteinase-9 (MMP-9) immunoreactive protein has modest prognostic
      value in locally advanced breast carcinoma patients treated with an adjuvant
      antiestrogen therapy.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are involved with tumour invasion
      and metastasis. Controversial data exists concerning the prognostic value of MMP
      9 in breast carcinoma. We examined, here, whether the MMP-9 immunoreactive
      protein would correlate with--the prognosis in breast carcinoma treated with
      hormonal adjuvant therapy. MATERIALS AND METHODS: The MMP-9 status was determined
      immunohistochemically from primary tumour specimens in 168 postmenopausal breast
      cancer patients with a locally advanced (N+) disease treated with antiestrogen
      for three years after the primary therapy. RESULTS: A positive immunostaining for
      MMP-9 was found in 61.3% of 168 primary tumours without any significant
      correlation to clinical stage, histology or hormone receptor status. MMP-9
      immunoreactivity did not correlate with the survival when the entire study
      population was included in the analysis. There was, however, a compromised
      disease-free survival in a subgroup of patients presenting with an estrogen
      receptor-negative and MMP-9-positive tumour. The 5-year disease-free survival was
      only 37% in those patients, when it was 63% in the patients with a tumour
      negative for both estrogen receptor and MMP-9. CONCLUSION: We suggest that the
      prognostic value of MMP-9 immunoreactivity in the primary tumour is not generally
      strong in breast carcinoma, but it might correlate with the clinical benefit of
      an antiestrogen therapy, since MMP-9 positivity seemed to correlate with early
      recurrence in patients with an estrogen receptor-negative primary tumour.

PMID- 15736481
TI  - Prognostic value of serum VEGF in melanoma patients: a pilot study.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in
      angiogenesis. We investigated the association of VEGF serum levels (pre-treatment
      and follow-up) with outcome in patients with melanoma. PATIENTS AND METHODS:
      Serum levels of VEGF in melanoma patients at diagnosis and during follow-up were
      analysed with enzyme-linked immunoassays. Patients were followed up with physical
      examination and ultrasound scans of the liver every three months and thorax X-ray
      annually. The VEGF serum level was evaluated six-monthly. RESULTS: From February
      1996 to February 2000, 33 patients were enrolled. Ninety-two serum blood samples
      were collected. Patients had a median age of 60 years (range 32-82). Twenty
      patients were males, 13 females. One patient presented with stage IA disease, 2
      with stage IB, 11 with stage IIA, 4 with stage IIB, 8 with stage III and 5 with
      stage IV. Two patients were affected by uveal melanoma. The melanomas were
      predominantly located at the extremities or trunk (26/33). The median serum level
      of VEGF at diagnosis was 249 ng/ml (minimum: 9 ng/ml, maximum: 1215 ng/ml). The
      median survival of all 33 patients was 45.1 months. The median time-to
      progression was 36.7 months. Patients with lower or higher serum VEGF values
      showed no statistically significant differences in survival. In contrast, high
      serum VEGF values were associated with shorter disease-free survival as compared
      with lower values (median DFS: 25 vs 60 months, p = 0.048 at log-rank test).
      CONCLUSION: Our results suggest that serum VEGF could be of prognostic value in
      melanoma.

PMID- 15736482
TI  - Loss of heterozygosity at chromosomes 3p and 17p in primary non-small cell lung
      cancer.
AB  - BACKGROUND: Loss of heterozygosity (LOH) of selected regions at chromosomes 3p
      and 17p in non-small cell lung cancer (NSCLC) and the association of these
      abnormalities with major clinical parameters and prognosis were studied.
      MATERIALS AND METHODS: The study group included 92 consecutive primary NSCLC
      tumours and four microsatellite markers from chromosome 3p and three markers from
      17p were analyzed. RESULTS: LOH of at least one locus was found in 83% of all
      analyzed tumours. Most frequently deletion (58%) was found at locus D3S1481
      (3p14.2). Sequence deletions of D17S520 (17p12) and TP53 (17p13.1) occurred in
      52% of tumours. LOH occurrence at 3p and 17p was more frequent in squamous cell
      carcinomas compared to adenocarcinomas (89% vs. 75%), but this difference was not
      significant. CONCLUSION: No significant association was found between LOH on any
      analyzed loci and tumour stage (TNM) and grade (G). There was no correlation
      between LOH and survival.

PMID- 15736483
TI  - Cosmetic procedure nurses to face new competencies.

PMID- 15736484
TI  - Confusion reigns in wake of new AfC overtime rules.

PMID- 15736485
TI  - Jane Warner a voice from primary care.

PMID- 15736486
TI  - Is personality disorder treatable? Yes.

PMID- 15736487
TI  - Is personality disorder treatable? No.

PMID- 15736488
TI  - Proving your competency.

PMID- 15736489
TI  - A new role in stroke care.

PMID- 15736490
TI  - How I coped with...a fire on the ward.

PMID- 15736492
TI  - What you need to know about Glaucoma.

PMID- 15736491
TI  - Communicable disease control during major emergencies.
AB  - In December 2004 a major disaster occurred in the Indian Ocean killing over
      150,000 people (USAID, 2005). This article will look at interventions required to
      control communicable diseases in an emergency. It is an introduction to emergency
      public health interventions for UK nurses who are responding to an international
      disaster.

PMID- 15736493
TI  - Pulse oximetry.

PMID- 15736494
TI  - Evaluating the development of a nurse-led discharge scheme.
AB  - This article reports on a project designed to develop nurse-led discharge at
      Winchester and Eastleigh Healthcare NHS Trust. For the purpose of the project,
      nurse-led discharge is the formal discharge by experienced nurses of patients
      from acute wards who meet the criteria previously agreed with the medical
      consultants - without further reference to the medical team. The progress of the
      project is outlined and recommendations are made for further development and
      dissemination throughout the trust.

PMID- 15736495
TI  - Aspirin.

PMID- 15736496
TI  - Maintenance of oral health in people with learning disabilities.
AB  - The oral health of people with learning disabilities is often compromised, which
      has a deleterious effect on their well-being. This article explores the need for
      specialist intervention. Barriers to effective care are scrutinised and potential
      solutions are suggested. As many people with learning disabilities are reliant
      upon their carers for the maintenance of their oral health, the article concludes
      with an analysis of advice to carers.

PMID- 15736497
TI  - The benefits of understanding the pathophysiology of anaemia.

PMID- 15736498
TI  - Palliative care for people with end-stage non-malignant lung disease.
AB  - Progressive non-malignant lung disease (PNMLD) is a common cause of morbidity and
      mortality in the UK. In 1999, chronic lung disease--including chronic obstructive
      pulmonary disease (COPD), tuberculosis, pulmonary circulatory disease,
      pneumonoconiosis, sarcoidosis and cystic fibrosis--killed almost 39,000 (British
      Thoracic Society, 2000), while it is estimated that 600,000 people in the UK have
      COPD, the most common non-malignant lung disease (BTS, 2001).

PMID- 15736499
TI  - Smoking cessation in pregnancy.
AB  - One in four pregnant women smokes throughout pregnancy and these women tend to be
      young, single, of lower educational achievement and in manual occupations. About
      25 per cent of pregnant smokers stop for part of their pregnancy, mostly within
      the first trimester, but 75 per cent return to smoking after the birth of their
      child (Owen and Penn, 1999).

PMID- 15736500
TI  - An audit of the management of acute asthma in accident and emergency.
AB  - It is estimated that 3.4 million people suffer from asthma in the UK, with
      640,000 having the condition in a severe or very severe form (Action on Smoking
      and Health, 2002). Asthma also accounts for 1,250 deaths annually (De Keyser,
      2002). Between 1980 and 1990 the prevalence of asthma in males increased by 114
      per cent and in females by 165 per cent (Respiratory Alliance, 2003).

PMID- 15736501
TI  - The nursing of a patient following lung volume reduction surgery.
AB  - Lung volume reduction surgery (LVRS) is an experimental surgical procedure that
      aims to alleviate the symptoms of breathlessness for patients with end-stage
      chronic emphysema. Emphysema (from the Greek for 'puff up') is a progressive
      chronic obstructive pulmonary disease (COPD) and risk factors include smoking and
      chronic infections. The disease causes the alveoli of the lung to over-expand and
      lose their elasticity (Schedel and Connolly, 1999). Advanced emphysema causes
      severe dyspnoea that significantly reduces the patient's quality of life.

PMID- 15736502
TI  - How to excel at a job interview.

PMID- 15736503
TI  - The patient's advocate in theatre.

PMID- 15736505
TI  - Why do kids get sick?

PMID- 15736504
TI  - 'We are reminded that everyone loves the NHS but nobody wants to pay for it'.

PMID- 15736506
TI  - The newest war on drugs.

PMID- 15736507
TI  - Conceiving ideas.

PMID- 15736508
TI  - Fidget? No! Walk? Yes!

PMID- 15736509
TI  - Health-care decision-making processes in Latin America: problems and prospects
      for the use of economic evaluation.
AB  - OBJECTIVES: The use of economic evaluation studies (EE) in the decision-making
      process within the health-care system of nine Latin American (LA) and three
      European countries was investigated. The aim was to identify the opportunities,
      obstacles, and changes needed to facilitate the introduction of EE as a formal
      tool in health-care decision-making processes in LA. METHODS: A comparative study
      was conducted based on existing literature and information provided through a
      questionnaire applied to decision makers in Argentina, Brazil, Colombia, Cuba,
      Mexico, Nicaragua, Peru, Portugal Spain, United Kingdom, Uruguay, and Venezuela.
      Systematic electronic searches of HEED, NHS EED, and LILACS were conducted to
      identify published economic evaluation studies in LA from 1982 onward. RESULTS:
      There is relatively little evidence of the conduct and use of EE within the
      health care systems in LA. Electronic searches retrieved 554 records; however,
      only 93 were EE. In the nine LA participating countries, broad allocation of
      health-care resources is primarily based on political criteria, historical
      records, geographical areas, and specific groups of patients and diseases. Public
      health provision and inclusion of services in health-insurance package are
      responsibilities of the Ministry of Health. Decisions regarding the purchase of
      medicines are primarily made through public tenders, and mainly based on
      differences in clinical efficacy and the price of health technologies of
      interest. CONCLUSIONS: To expedite the process of incorporating EE as a formal
      tool to inform decision-making processes within the health-care systems in LA
      countries, two main conditions need to be fulfilled. First, adequate resources
      and skills need to be available to conduct EE of good quality. Second, decision
      making procedures need to be modified to accommodate "evidence-based" approaches
      such as EE.

PMID- 15736510
TI  - Systematic review of economic evidence on stroke rehabilitation services.
AB  - OBJECTIVES: Given the resource-intensive nature of stroke rehabilitation, it is
      important that services be delivered in an evidence-based and cost-efficient
      manner. The objective of this review was to assess the evidence on the relative
      cost or cost-effectiveness of three rehabilitation services after stroke: stroke
      unit care versus care on another hospital ward, early supported discharge (ESD)
      services versus "usual care," and community or home-based rehabilitation versus
      "usual care." METHODS: A systematic literature review of cost analyses or
      economic evaluations was performed. Study characteristics and results (including
      mean total cost per patient) were summarized. The level of evidence concerning
      relative cost or cost-effectiveness for each service type was determined
      qualitatively. RESULTS: Fifteen studies met the inclusion criteria: three on
      stroke unit care, eight on ESD services, and four on community-based
      rehabilitation. All were classified as cost-consequences analysis or cost
      analysis. The time horizon was generally short (1 year or less). The comparators
      and the scope of costs varied between studies. CONCLUSIONS: There was "some"
      evidence that the mean total cost per patient of rehabilitation in a stroke unit
      is comparable to care provided in another hospital ward. There is "moderate"
      evidence that ESD services provide care at modestly lower total costs than usual
      care for stroke patients with mild or moderate disability. There was
      "insufficient" evidence concerning the cost of community-based rehabilitation
      compared with usual care. Several methodological problems were encountered when
      analyzing the economic evidence.

PMID- 15736511
TI  - Measuring cost-effectiveness of secondary health care: feasibility and potential
      utilization of results.
AB  - OBJECTIVES: Whether cost-effectiveness of secondary health care can be measured
      in a simple, yet commensurate way was studied. METHODS: Approximately 4,900
      patients' health-related quality of life scores before and after treatment were
      measured. Used were a combination of quality of life data with diagnostic and
      financial indicators routinely collected in the hospital. RESULTS: Seventy
      percent of patients returned the first questionnaire and the informed written
      consent to participate. Of these patients, 80 percent also returned the second
      questionnaire sent out 3 to 12 months after treatment, depending on clinical
      specialty and diagnostic category. The routine of sending out questionnaires
      could be automated in such a way that data collection required only a limited
      amount of extra work. Patients were generally satisfied with the fact that the
      hospital was interested in their well-being also after treatment. No physician
      offered the chance to participate refused data collection in the patient group he
      or she was responsible for. The attitudes of the nursing staff were generally
      positive toward data collection, although it caused some extra work for some of
      them. The possibility of relating already routinely collected financial
      performance indicators with a relevant measure of treatment effectiveness, opened
      prospects for refined analysis of cost-effectiveness of secondary health care.
      CONCLUSIONS: Routine collection of health-related quality of life data as an
      indicator of treatment effectiveness is feasible, requires only a small amount of
      extra work, and is potentially very useful when combined with existing measures
      of hospital performance.

PMID- 15736512
TI  - Hemodialysis for end-stage renal disease: a cost-effectiveness analysis of
      treatment-options.
AB  - BACKGROUND: During 2001, over 32,000 patients in the United Kingdom received
      renal replacement therapy (RRT). Approximately half had a functioning transplant,
      with the remainder receiving dialysis therapy. The main form of dialysis is
      hemodialysis (HD), which is provided to 37.1 percent of the RRT population. HD is
      provided in three main settings: hospital (24.5 percent), satellite (10.9
      percent), or home (1.7 percent). The objective of this study is to explore the
      cost-effectiveness of these different modalities. METHODS: By using clinical and
      cost data from a systematic review, a Markov model was developed to assess the
      costs and benefits of the three different modalities. The model included direct
      health service costs and quality-adjusted life years (QALYs). Sensitivity
      analyses were performed to assess the robustness of the results. RESULTS:
      Satellite HD has lower costs 46,000 pounds sterling and 62,050 pounds sterling at
      5 and 10 years than home HD 47,660 pounds sterling and 63,540 pounds sterling.
      The total effectiveness of home HD was slightly greater than for satellite HD, so
      the incremental cost per QALY of home versus satellite HD was modest at 6,665
      pounds sterling at 5 years and 3,943 pounds sterling at 10 years. Both modalities
      dominated hospital HD. CONCLUSIONS: Results from the study reveal that satellite
      HD was less costly than home HD, and home HD was less costly than hospital HD.
      The lack of robust data on the effectiveness and new dialysis equipment, which
      were not included in this review, throws some caution on these results.
      Nonetheless, the results are supportive of a shift from hospital HD to satellite
      and home HD.

PMID- 15736513
TI  - Economic evaluation of hemodialysis: implications for technology assessment in
      Greece.
AB  - OBJECTIVES: Hemodialysis is a well-established treatment for 74 percent of end
      stage renal disease (ESRD) patients in Greece. The purpose of this study is to
      provide an estimate of the direct cost of dialysis in a public hospital setting
      and an estimate of the loss of production for ESRD patients. The results will be
      useful for public health facility planning purposes. METHODS: A socioeconomic
      prevalence-based analysis was performed using micro-economic evaluation of health
      care resources consumed to provide hemodialysis for ESRD patients in 2000. Lost
      productivity costs due to illness were estimated for the patient and family using
      the human capital approach and the friction method. Indirect morbidity costs due
      to absence from work and long-term were estimated, as well as mortality costs.
      Mean gross income was used for both patient and family. RESULTS: Total health
      sector cost for hemodialysis in Greece exceeds 171 million Euros, or 182 Euros
      per session and 229 Euros per inpatient day. There were 2,046 years lost due to
      mortality, and the potential productivity cost was estimated at 9.9 million
      Euros, according to the human capital approach, and 303.000 Euros, according to
      the friction method. Total morbidity cost due to absence from work and early
      retirement was estimated at more than 273 million Euros, according to the human
      capital approach, and 12.5 Euros, according to the friction method. CONCLUSIONS:
      Providing hemodialysis care for 0.05 percent of the population suffering from
      ESRD absorbs approximately 2 percent of total health expenditure in Greece. In
      addition to the cost for the National Health System, production loss due to
      mortality and morbidity from the disease are also considerable. Promoting
      alternative technologies such as organ transplantation and home dialysis as well
      as improving hemodialysis efficiency through satellite units are strategies that
      may prove more cost-effective and psychologically advantageous for the patients.

PMID- 15736514
TI  - Clinical- and cost-effectiveness of pegylated interferon alfa in the treatment of
      chronic hepatitis C: a systematic review and economic evaluation.
AB  - OBJECTIVES: To assess the clinical-effectiveness and cost-effectiveness of
      pegylated interferon alfa (2a and 2b) combined with ribavirin in previously
      untreated patients with moderate to severe chronic hepatitis C, compared with the
      current standard treatment, which is nonpegylated interferon alfa combined with
      ribavirin. METHODS: Systematic review and economic evaluation. A sensitive search
      strategy was applied to several electronic bibliographic databases. Relevant
      studies were critically appraised and meta-analyzed. A hypothetical cohort of
      1,000 patients entered a Markov model and were followed up for a more than 30
      year period to predict natural history, duration spent in each health state, and
      treatment costs. RESULTS: Two fully published Phase III randomized controlled
      trials were included. Methodological quality was generally good. Dual therapy
      with pegylated interferon was significantly more effective than nonpegylated dual
      therapy with a pooled sustained virological response rate (SVR) of 55 percent (95
      percent confidence interval [CI], 52-58 percent) compared with 46 percent (95
      percent CI, 43-49 percent). The pooled relative risk of remaining infected was
      0.83 (95 percent CI, 0.76-0.91 percent). Genotype was the strongest predictor of
      outcome, with SVRs in patients with the more responsive genotypes 2 and 3
      reaching up to 80 percent. The incremental cost per quality-adjusted life year
      (QALY) for pegylated dual therapy compared with nonpegylated dual therapy was
      12,123 pounds sterling. The cost per QALY remained under 30,000 pounds sterling
      for most patient subgroups and in sensitivity analyses. CONCLUSIONS: Pegylated
      interferon is clinically effective, represents good value for the money, and is a
      significant advance in the treatment of this insidious disease.

PMID- 15736515
TI  - Effectiveness and cost-effectiveness of initial combination therapy with
      interferon/peginterferon plus ribavirin in patients with chronic hepatitis C in
      Germany: a health technology assessment commissioned by the German Federal
      Ministry of Health and Social Security.
AB  - OBJECTIVES: The purpose of this health technology assessment (HTA), commissioned
      by the German Federal Ministry of Health and Social Security, was to
      systematically review the evidence for the effectiveness and cost-effectiveness
      of antiviral treatment (AVT) with interferon (INF) or peginterferon (PegIFN) in
      combination with ribavirin (RBV) in treatment-naive patients with chronic
      hepatitis C (CHC) and to apply these data in the context of the German health
      care system. METHODS: We performed a systematic literature search on
      effectiveness and cost-effectiveness of AVT and summarized results using meta
      analysis and evidence tables. We applied the German Hepatitis C Model (GEHMO), a
      decision-analytic Markov model, to determine long-term clinical effectiveness,
      costs, and incremental cost-effectiveness ratios (ICER) of the examined treatment
      strategies. Model parameters were derived from German databases, published
      international randomized clinical trials (RCT), and a Cochrane Review. RESULTS:
      Overall, nine RCTs, two HTA reports, one Cochrane review, two meta-analyses, and
      seven economic evaluations met the inclusion criteria. These studies indicate
      that PegIFN + RBV achieved the highest sustained virological response rates (SVR)
      (54-61 percent), followed by IFN + RBV (38-54 percent) and IFN monotherapy (11-21
      percent). Based on our meta-analysis, PegIFN + RBV reduced cases without SVR by
      17 percent compared with INF + RBV. International cost-effectiveness studies
      indicate that INF+ RBV is cost-effective when compared with INF monotherapy. For
      PegIFN + RBV, our decision analysis yielded an ICER of 9,800 Euros per quality
      adjusted life-year gained. CONCLUSIONS: This HTA suggests that initial
      combination therapy prolongs life, improves quality of life, and is cost
      effective in patients with CHC. Peginterferon plus ribavirin is the most
      effective and efficient treatment among the examined options. However, because
      not all chronic hepatitis C patients will develop progressive liver disease, a
      thorough assessment of the eligibility and appropriateness of treatment with
      combination therapy must be performed in each individual patient.

PMID- 15736516
TI  - Assessing the in-hospital survival benefits of intensive care.
AB  - OBJECTIVES: For an efficient and fair allocation of medical resources, one must
      know which patients benefit more from medical care. The objective of this study
      is to assess the differential survival benefits of a general intensive care unit
      (ICU) by acute diagnoses and by Acute Physiological and Chronic Health Evaluation
      (APACHE II) scores. METHODS: The sample included all patients triaged for
      admission to the Hadassah-Hebrew University Medical Center ICU during a 7-month
      period (n = 381). The potential effect of ICU on in-hospital survival was
      estimated by a bivariate (admission-survival) probit model, using crowding in the
      unit as the identifying variable, controlling for observable patients
      characteristics: age, sex, acute diagnoses, and APACHE II score. Using the
      estimates, the differential predicted survival benefits of ICU were calculated
      for selected general acute diagnoses and for different APACHE II scores. RESULTS:
      Adjusting for age, sex, and general acute diagnoses, the average potential
      survival benefit of ICU is 17 percentage points (pts). The benefit of ICU for
      patients with central nervous system problems, with sepsis, or with respiratory
      failure are higher than average (23 pts). Adjusting for APACHE II scores as well
      increases the estimated average potential benefit to 21 pts. Over the range of
      APACHE II scores, the highest benefit (38 pts of potential benefit) is attained
      for patients with scores around 22. CONCLUSIONS: Survival benefits differ across
      diagnoses and APACHE II scores. Facing limited resources, admission policies
      should distinguish between survival probabilities (and survival maximization) and
      survival benefits (and maximization of ICU benefits). Actual referral and
      admission policies to the present ICU do not maximize the potential survival
      benefits of ICU resources.

PMID- 15736517
TI  - Determinants of the diffusion of computed tomography and magnetic resonance
      imaging.
AB  - OBJECTIVES: The aim of this study is to explain factors influential to the
      diffusion of computed tomography (CTs) and magnetic resonance imaging (MRIs).
      METHODS: Variables were identified from a review of the literature on the
      diffusion of health technologies. A formal process was applied to build a
      conceptual model of the mechanism that drives technology diffusion. Variables for
      the analysis were classified as predisposing, enabling, or reinforcing factors,
      in keeping with a model commonly used to explain the diffusion of health
      behaviors. Multiple regression analysis was conducted using year 2000 OECD data.
      RESULTS: The results of this study showed that total health expenditure per
      capita (p < .01, both CTs and MRIs) and flexible payment methods to hospitals (p
      < .05, both CTs and MRIs) were significantly associated with the diffusion of CTs
      and MRIs (adjusted R2 = 0.477, 0.656, respectively). CONCLUSIONS: This study
      presents a systematically developed model of the mechanism governing technology
      diffusion. Important findings from the study show that purchasing power,
      represented by total health expenditure per capita and economic incentives to
      hospitals in the form of flexible payment methods, were positively correlated
      with diffusion. Another important achievement of our model is that it accounts
      for all thirty OECD member countries without excluding any as outliers. This
      study shows that variation across countries in the diffusion of medical
      technology can be explained well by a logical model with multiple variables, the
      results of which hold profound implications for health policy regarding the
      adoption of innovations.

PMID- 15736518
TI  - Determinants of computed tomography and magnetic resonance imaging utilization in
      Taiwan.
AB  - OBJECTIVES: Magnetic resonance imaging (MRI) and computerized tomography (CT)
      scanners are high-tech equipment with the highest utilizations and expenditures
      in Taiwan. This study investigates the factors that affect MRI and CT
      utilization, such as whether supply-side factors have more impact than demand
      side factors, and the effect of utilization control policies. METHODS: This study
      used the nationwide CT and MRI claim data for the years 1998 to 2001 from the
      Bureau of National Health Insurance (BNHI) in Taiwan. Multiple regression
      analysis was the statistical method used to determine the relative factors that
      influence CT and MRI utilization. RESULTS: CT: population ratio, hospital-based
      physician: population ratio, female ratio, pediatric (< or =14 years) :
      population ratio, and family income significantly influenced CT utilization. MRI
      : population ratio and hospital-based physician : population ratio, female ratio,
      and family income significantly influenced MRI utilization. However, the
      proportion of the aged (> or =65 years of age) did not significantly influence CT
      or MRI utilization after controlling for other factors. The rates of CT and MRI
      utilization for the outpatient and inpatient settings and the repeated uses of CT
      or MRI have decreased significantly after a utilization review was implemented by
      BNHI, which suggests that CT and MRI have been overused. CONCLUSIONS: Increases
      in supply-side factors significantly increase CT/MRI utilization, and supply-side
      factors impact CT/MRI utilization more than demand-side factors. The results show
      that the utilization instant report policy effectively decreases repeated uses of
      CT/MRI.

PMID- 15736519
TI  - International comparison of the definition and the practical application of
      health technology assessment.
AB  - OBJECTIVES: Health Technology Assessment (HTA) is defined as a policy research
      approach that examines the short- and long-term social consequences of the
      application or use of technology. Internationally different institutions have
      translated this definition to local contexts. In Denmark, HTA is comprehensive
      with focus on four aspects of the problem in question (technology [clinical
      evidence], economy, patient, and organization). The objective of this study is to
      study how the application of HTA differs across leading countries and to study
      the extent to which Danish HTA reports differ from foreign HTAs. METHODS: A
      sample of 433 HTA reports published in the period 1989--2002 by eleven leading
      institutions or agencies in Denmark and eight other countries were reviewed. We
      looked at the characteristics of the HTA with respect to focus on the four main
      aspects and the manner in which each aspect has been approached. RESULTS: The
      study shows health technology procedures to be the most common type of health
      technology assessed in HTAs and literature review to be the most often used
      method of analysis. Policy recommendations are only present in approximately half
      of the HTA reports. CONCLUSIONS: In the HTAs one generally sees a great focus on
      the clinical aspect of health technologies, leaving the economic, the patient
      related, and the organizational aspect much more unanalyzed. The Danish HTAs
      generally have a wider scope than HTAs produced in other countries and tend to
      focus more frequently on patient-related and organizational dimensions.

PMID- 15736520
TI  - Can health technologies be assessed using routine data?
AB  - OBJECTIVES: The potential of routine data for health technology assessment (HTA)
      in the United Kingdom was assessed. METHODS: Compiled were a comprehensive list
      of routine databases, their classification according to data characteristics,
      literature review on their current use, and their comparison with key topics
      identified as priorities for HTA. RESULTS: Two hundred seventy health-care
      databases for England or the English regions were identified. Twenty-four
      included data on both health technology and patient health state. Eleven found
      some published use in effectiveness evaluation. Of 140 prioritized health
      technologies, only 22 could be identified in routine databases. CONCLUSIONS:
      Routine data are plentiful but of limited use in HTA. The data sets usually do
      not include the effect of treatments. Coding is inadequate, and confidentiality
      regulations will make matters worse. Both need urgent attention.

PMID- 15736521
TI  - International Master's Program in health technology assessment and management:
      assessment of the first edition (2001--2003).
AB  - BACKGROUND: Despite a clear call for greater input from health technology
      assessment (HTA) in the areas of clinical practice and policy making, there are
      currently very few formal training programs. The objectives of our Consortium
      were to (i) develop a master's level program in HTA, (ii) test its content with a
      group of Canadian and European students, and (iii) evaluate the Program's
      strengths and weaknesses. OBJECTIVES: This study presents the results of our
      evaluation of the first edition of the Master's Program (2001--2003). METHODS:
      The evaluation relied on (i) a self-administered student questionnaire for each
      course (n = 142), (ii) interviews with students (n = 10), and (iii) interviews
      with internship supervisors (n = 5). RESULTS: A vast majority of students were
      satisfied with the course content and particularly appreciated the exercises and
      materials presented in an intensive format. However, they needed more systematic
      feedback from faculty members and recommended increasing the methodology content.
      The six key characteristics of the program are (i) flexible format adapted to the
      needs of skilled professionals, (ii) continuous interaction between HTA users and
      producers, (iii) international academic and professional collaboration, (iv)
      partnership with HTA agencies, (v) global approach to evidence-based methods and
      practices, and (vi) multidisciplinary approach. CONCLUSIONS: Despite the numerous
      organizational barriers inherent to creating an international program and several
      areas for improvement in the Program itself, the Ulysses Project was successful
      in attaining its objectives. Because there is a growing need for human resources
      with special training in HTA, further efforts need to be devoted to strengthening
      the international research capacity in HTA.

PMID- 15736522
TI  - Validity of utilities of patients with esophageal cancer.
AB  - OBJECTIVES: The convergent validity between utility assessment methods was
      assessed. METHODS: Investigated were patients with esophageal cancer treated
      surgically with curative intent. Patients were interviewed in a period from 3 to
      12 months after surgical resection. Patients evaluated their actual health and
      seven other states. Visual analogue scale (VAS) and standard gamble (SG)
      utilities were obtained for the health states in an interview. Patients also
      indicated whether or not they preferred death to living in a health state (worse
      than dead [WTD] preferences). RESULTS: Fifty patients completed the interview.
      Convergent validity was excellent at the aggregate and individual level. However,
      the relation between VAS and SG differed strongly across individuals. On a scale
      from 0 (dead) to 100 (perfect health), SG scores were lower for patients with WTD
      preferences (mean difference d = 35; p = .002); however, VAS scores did not vary
      by WTD preferences. CONCLUSIONS: In general, there is good agreement between VAS
      and SG measures, although patients disagree about how the VAS and SG are related.
      The standard gamble varied by WTD preferences, however, the VAS did not.

PMID- 15736523
TI  - Meta-analysis when only the median survival times are known: a comparison with
      individual patient data results.
AB  - BACKGROUND: The hazard ratio (HR) is the most appropriate measure for time to
      event outcomes such as survival. In systematic reviews, HRs can be calculated
      either from the raw trial data obtained as part of an individual patient data
      (IPD) meta-analysis or from the appropriate trial-level summary statistics.
      However, the information required for the latter are seldom reported in
      sufficient detail to allow reviewers to calculate HRs. In contrast, the median
      survival and survival rates at specific time points are frequently presented. We
      aimed to evaluate retrospectively the performance of meta-analyses using median
      survival times and survival rates by comparing them with meta-analyses using IPD
      to calculate HRs. METHODS: IPD from thirteen published meta-analyses (MAs) in
      cancers with high mortality rates were used. Median survival and survival rates
      were calculated from the IPD rather than taken from publications so that the same
      trials, patients, and extended follow-up are used in each analysis. RESULTS AND
      CONCLUSIONS: We show that using median survival times or survival rates at a
      particular point in time are not reasonable surrogate measures for meta-analyses
      of survival outcomes and that, wherever possible, HRs should be calculated.
      Individual trial publications reporting on time to event outcomes, therefore,
      should provide more detailed statistical information, preferably logHRs and their
      variances, or their estimators.

PMID- 15736524
TI  - Cost-effectiveness analysis of medical documentation alternatives.
AB  - OBJECTIVES: The delay between patient discharge and the completion of the final
      discharge note have prompted hospitals to consider new information technologies.
      This study compared the relative cost-effectiveness of an automated medical
      documentation system to the current system in place at a Canadian hospital. There
      are significant expenditures associated with the choice of medical documentation
      system, yet the benefit to the patient population has not been studied. METHODS:
      A systematic review of the literature was carried out. Cost data for the current
      documentation system were obtained from the study hospital. The costs of
      purchasing the automated system were obtained from the manufacturer. Other
      resource cost implications of the automated system were estimated based on
      information obtained from the Centre for Applied Health Informatics at the study
      hospital. The outcome was determined to be the average time (days) between
      patient discharge and note completion. A cost-effectiveness analysis was
      conducted. Sensitivity analyses were used to determine the robustness of the
      results. RESULTS: The automated documentation system was associated with higher
      costs but better outcomes than the current system. The incremental cost
      effectiveness ratio used for comparing the automated medical documentation system
      with the traditional system indicated that the incremental daily cost for
      decreasing a day in average note completion time per discharge note was 0.331
      Canadian $/day over the study period (4 years). CONCLUSIONS: Although the
      automated documentation system was more expensive than the current system, it
      also provided qualitative benefits that were not considered in the cost
      effectiveness analysis.

PMID- 15736525
TI  - Cost-effectiveness of Herceptin: a standard cost model for breast-cancer
      treatment in a Belgian university hospital.
AB  - OBJECTIVES: The objective of this study was to conduct a cost-effectiveness
      analysis of Herceptin from the hospital's point of view. This new
      biotechnological pharmaceutical is a humanized monoclonal antibody that targets
      the HER2 receptor, an important anti-cancer target. METHODS: A cost model with
      standard diagnostic and treatment options for breast cancer was set up for a
      Belgian university hospital in close collaboration with its specialists. Direct
      and indirect costs were calculated for each diagnostic and treatment option using
      the micro-costing method. Effectiveness was estimated through a literature study.
      The model allowed us to take cost consequences in other stages of the model into
      account and to calculate changes in monthly treatment costs from different
      "starting points." With an incremental cost-effectiveness analysis, differences
      in costs and effectiveness with and without Herceptin were compared. RESULTS:
      Over the complete treatment period from diagnosis until the metastatic phase,
      monthly costs for the hospital rose from 85.07 Euros to 90.35 Euros for stage I
      diagnosed breast cancer when adding Herceptin to the model. In the metastatic
      phase alone, these costs rose from 1,132.33 Euros to 1,256.23 Euros. With
      Herceptin, we found an extra cost of 3,981.44 Euros per extra life-month.
      CONCLUSIONS: This cost-effectiveness ratio was rather high, because Herceptin was
      quite expensive and the product was additive in its current use and did not
      replace existing treatments. Future research will concentrate on alternative
      applications of Herceptin based on ongoing Herceptin trials and expert opinions.

PMID- 15736526
TI  - Can electronic routine data act as a surrogate for patient-assessed outcome
      measures?
AB  - OBJECTIVES: There has been a rapid growth in the use of patient-assessed outcomes
      (PAOs) that are measured in the assessment of health technologies. The process of
      collection of such measures can be costly, and there may be problems associated
      with the ability of the patient to complete them. The use of electronically
      stored routine data may reduce costs and overcome the problems associated with
      patient completion. The feasibility of using routine data surrogates for the UK
      Inflammatory Bowel Disease Questionnaire (UKIBDQ) and the Short Form 36 (SF-36)
      was examined. METHODS: Clinical terms and codes for the UKIBDQ and SF-36
      questions were identified, and data from electronic routine sources were sought
      on patients participating in a randomized controlled trial. The presence or
      absence of relevant symptoms was used to generate surrogate scores, which were
      compared with the original scores. RESULTS: Most questions in the UKIBDQ and SF
      36 were codable but only one third of the terms were recorded routinely in
      electronic form. The surrogate total IBDQ score had reasonable reliability (Kuder
      Richardson coefficient = 0.51), but this reliability could not be determined for
      the SF-36. Intraclass correlations between routine and designed data were poor to
      weak. CONCLUSIONS: Although electronic routine data sources had the capacity to
      develop surrogate measures for patient assessed outcomes, there was evidence of
      wide underutilization of coding systems leading to an underreporting of symptoms.
      This finding is consistent with previous literature where only poor correlations
      were illustrated between patient assessed outcomes and surrogate scoring of
      symptoms.

PMID- 15736527
TI  - Double-blind randomized control trial in acute carbon monoxide poisoning.

PMID- 15736528
TI  - [Social inequalities in health: how to combine clinical and populational
      approaches].

PMID- 15736529
TI  - [Visceral leishmaniases].
AB  - Visceral leishmaniases (VL), with spreading epidemics in India and Sudan, and
      sporadic cases in mediterranean basin, show clinical, therapeutical and public
      health aspects varying according to the geographic context. Co-infection of VL
      with the human immunodeficiency virus emerged in southwestern Europe and could
      occur in a next future in India, in Sudan, in Ethiopia or in Brazil. Today, lipid
      formulations of amphotericin B should be the first line drugs in Mediterranean
      basin. Elsewhere, pentavalent antimonials remain the cornerstone of treatment in
      non resistant areas, conventional amphotericin B or miltefosine being an
      alternative in areas of resistance to antimony.

PMID- 15736530
TI  - [Social inequalities in health. A dossier to be reopened].

PMID- 15736531
TI  - [The origins and foundations of social inequalities in health].
AB  - France presents the paradox of being the country where the health system has been
      ranked first in the world for its overall performance and where the inequalities
      of mortality among men are the highest in Western Europe. This reality is little
      known, in part because it is little studied. The authors show how the issue of
      health inequalities has been recently re-discovered by researchers and scientific
      institutions. They attempt to explain the reasons of the delay in comparison with
      neighbour countries, referring to its historical background. They explore how
      health inequalities, long considered as natural, have progressively been seen as
      social. The problem of definition and qualification is therefore of the utmost
      importance. Two conditions are necessary to speak of inequalities and not mere
      differences: the domain has to be socially valued (life or wellbeing, for
      instance) and the disparities must be hierarchical (social classes, occupational
      categories, etc.). Finally, the authors recall that the social inequalities in
      health are the result of structural inequalities which concerns all the fields of
      social activities and conditions and which reflects the level of social justice
      in a country at a specific moment of its history and economic development.

PMID- 15736532
TI  - [Socio-economic differences in mortality].
AB  - The ranking and frequency of the different causes of death vary according to
      social categories. The largest disparities in mortality are observed, at first
      for causes linked to alcohol consumption; then for diabetes, respiratory
      diseases, lung cancer, cerebrovascular diseases, stomach cancer, suicide,
      accidents, myocardial infarction, intestine and pancreas cancer. For most of the
      causes of death, there is an increase in time trends in the level of the over
      mortality of the group "manual workers-clerical" in comparison with the group
      "high level professional workers". European comparisons outlined that France and
      Finland have the more marked social differences in mortality. For France, this
      trend concerns all the causes of death apart from cardiovascular diseases and
      violent deaths. The role of excessive alcohol consumption is outlined as an
      explanation of this specific position of France.

PMID- 15736533
TI  - [A research into the determinants of socio-economic differences in health].
AB  - The aim of this article is to explain the permanence and even the aggravation of
      health social inequalities, which concerns all age groups. One can regroup the
      causes of these inequalities into four main categories of inter-dependant
      variables, acting in synergy with a cumulative effect :1. accumulated capital,
      i.e. cultural, social, economical and health, acquired during the adult age; 2.
      conditions of employment and work; 3. conditions and atmosphere of daily life; 4.
      style and way of life. The worries, stresses and anxieties, compounded together
      with the whole of the above variables which, acting back on themselves, will
      therefore emphasise, whether favourable or not, their effects on the state of
      health of the individuals concerned. The social inequalities of health are,
      therefore, the results of the whole group of inequalities; practically all are
      hierarchically identical. An aggravation of the socioeconomic differences of all
      types leads, as a result, to inequality of health and social reproduction which
      is always pregnant in our society. This explains socio-economic differentials in
      health and mortality from one generation to the next.

PMID- 15736534
TI  - [Disabilities and social inequalities].
AB  - This article deals with disabilities in the light of social inequalities. The
      three constitutive levels of disabilities, as defined by Wood, are successively
      studied: impairments deficiencies, disabilities incapabilities, and
      disadvantages. The results, coming from the first French national survey on
      disabilities, show that impairments deficiencies are more frequent at the lower
      end of the social scale. These inequalities increase when sequentially
      considering impairments deficiencies, disabilities, incapabilities and then
      disadvantages. The scope of inequalities observed at these three levels makes us
      questioning the efficiency of the programmes aimed at correcting for
      disabilities.

PMID- 15736535
TI  - [Work and social inequalities in health: the case of professional cancers].
AB  - Work plays a major role in the production of social inequalities in health in two
      ways. It determines the place that each one is occupying in the production and in
      the society, which is influencing the social inequalities as regards living
      conditions, income, housing, social security and access to the healthcare. In
      addition, the conditions and the organization of work have direct effects on
      worker's health according to the types of social division of work and of
      occupational hazards. The social differentiation of the occupational exposure to
      carcinogenic substances is under the influence of such a social division of work
      which plays also a role in the production of the inequalities in cancer. Known
      since decades, such inequalities are generally considered as related to the
      individual behaviours. The role of work in the social construction of these
      inequalities is little questioned, even if epidemiological data exist concerning
      occupational cancer. These are not visible in public area and little recognised
      in occupational disease. French and European regulations are taking in account
      the prevention of occupational cancer, but the effective practices are still
      poorly developed. This article attempts to show what is the state of the problem
      in terms of knowledge, compensation and prevention of these cancers which are
      related to work and for a large part invisible. This invisibility is contributing
      to the social growth of social inequalities in cancer.

PMID- 15736536
TI  - [Social inequalities in terms of health and problems experienced in childhood].
AB  - Health-related social inequalities are aggravated by whether or not people have
      suffered "severe problems" during childhood. Vulnerability to illness linked to
      such problems is most significant among underprivileged populations. Moreover,
      while childhood difficulties affect all social levels, they are more frequent
      among the most deprived individuals. The article points out how these results
      have already been brought to light on samples derived from three major surveys
      conducted by INSEE between 1978 and 1992. It then draws from the surveys
      conducted from 1994 to 1997 by CREDES to present their more in-depth analyses
      explaining three of the processes through which people stating that they
      experienced problems in their childhood find themselves in a worse state of
      health: this fact is linked with higher risk-taking, which is, in itself, often
      pathogenic; it often aggravates the consequences of recent unfortunate events in
      terms of morbidity; in addition, the protection afforded by the memory of
      problems experienced during childhood diminishes in keeping with the educational
      level.

PMID- 15736537
TI  - [Social inequalities in health: what could be done in general practice?].
AB  - Because of specific features of his practice (comprehensive access to different
      social classes, provision of care for the whole set of diseases, length of follow
      up) general practitioner is in a privileged position to give evidence and can act
      against social inequalities in health. Understand and measure the effects of
      social characteristics on patients health is the first action to be done because
      the clinical description and the natural history of these inequalities are in
      fact very roughly known. The general practitioner can further act by learning how
      to concentrate his work to increase quality of care among male patients in
      workers and clerical or service staff categories, ensuring that needs are met as
      far as possible. Initiation of this work is the task of teaching practitioners
      and health care networks and provide a subject for primary care research. As a
      general rule, differences between social groups for the frequency or the
      prognosis of a given disease will be associated with, all together, accumulation
      of 'classical' risk factors for the considered disease, inequalities in care
      uptake partially due to a socially patterned access to the specialists, and an
      element of residual vulnerability, non explained by the previous two, which is
      the matter for an active research at the present time.

PMID- 15736538
TI  - [Social inequalities in health].

PMID- 15736539
TI  - [Patient card: universal health insurance].

PMID- 15736540
TI  - [The unicity of the wheel].

PMID- 15736541
TI  - [Hemoptysis].

PMID- 15736542
TI  - [Hernia of the abdominal wall in child and adult].

PMID- 15736543
TI  - [Sexuality and problems in sexuality].

PMID- 15736544
TI  - [Organ transplantation: epidemiological and immunological aspects; principles of
      treatment and surveillance; complications and prognosis; ethical and legal
      aspects].

PMID- 15736545
TI  - [Infectious pathology in migrants].

PMID- 15736546
TI  - [Etienne-Jules Marey, from the graphic method to the cinematograph].

PMID- 15736547
TI  - Open access and the developing world.

PMID- 15736548
TI  - Utilization of and barriers to public sector tuberculosis services in India.
AB  - BACKGROUND: Tuberculosis control in India still faces many challenges related to
      the provision of services under the Directly Observed Treatment, Short-course
      (DOTS) strategy. We assessed the utilization of and barriers to the Revised
      National Tuberculosis Control Programme (RNTCP) services based on DOTS in 4
      states of India, and recommend actions to optimize utilization of the RNTCP
      services. METHODS: Two districts each in 4 states with more than 50% of the
      population covered under the RNTCP in 2002, representing diverse levels of
      general health indicators, were selected. Sex-disaggregated data on patients who
      reported to the RNTCP facilities for the diagnosis and treatment of tuberculosis
      in 2002 were reviewed from the laboratory and tuberculosis registers to assess
      the utilization of these services. Data on barriers to utilization of the RNTCP
      services were collected through interviews of 4310 patients with tuberculosis who
      were 16 years of age or older. RESULTS: A total of 83,099 patients had reported
      for the diagnosis of tuberculosis in the study areas, of whom 29,279 were women
      (35.2%). The proportion of sputum-positive diagnosis was lower in women (10.8%
      [95% CI 10.5%-11.1%]) than men (17% [95% CI 16.7%-17.3%]). For the treatment of
      tuberculosis, 21592 patients were registered in the study areas; 6789 were women
      (31.4%). Among new smear-positive tuberculosis patients, 79.9% of women (95% CI
      78.4%-81.4%) and 74.4% of men (95% CI 73.4%-75.4%) were cured. Multivariate
      analysis revealed that the odds of not completing the process of diagnosis of
      tuberculosis were significantly higher for patients > 50 years of age, those who
      were never married or married currently, those with symptoms for < or = 15 days,
      those who had gone alone for diagnosis, and those who were not informed about a
      suspicion of tuberculosis by the health personnel at the time of diagnosis. Among
      the reasons for not completing the process of diagnosis of tuberculosis, health
      provider-related barriers were cited most frequently (45.9%), followed by
      improvement in symptoms. Health provider-related barriers were also cited most
      frequently (40.4%) by those who had completed the process of diagnosis but did
      not start treatment in the RNTCP facility. On multivariate analysis, the odds of
      not completing the treatment of tuberculosis were significantly higher for men,
      those who were ever married, those who were not informed that tuberculosis was
      curable, those who were not informed of the duration of treatment at the time of
      starting treatment, those who were dissatisfied with the DOTS provider, and those
      who had health facility staff as the DOTS provider compared with those who had an
      anganwadi/health worker. Medicine-related barriers were cited most frequently by
      patients who had defaulted in the intensive (37.1%) or continuation (23.1%) phase
      of treatment. CONCLUSION: Of the persons utilizing the RNTCP services, about one
      third are women. The health services-related factors indicated in the
      multivariate analysis for less than optimal utilization of the RNTCP services,
      and the health provider-related and treatment-related barriers to utilization of
      the RNTCP services at various levels cited by the patients suggest the need to
      adopt a patient-centred approach to improve utilization of the RNTCP services.

PMID- 15736549
TI  - Hypertension in the native rural population of Assam.
AB  - BACKGROUND: Recent studies have reported an increasing prevalence of hypertension
      in India. However, there are few epidemiological data with regard to the
      occurrence of hypertension in the native population of Assam. METHODS: Three
      thousand one hundred and eighty individuals (1441 men and 1739 women), > or =30
      years of age and from 25 villages of 5 districts in Assam were selected by the
      stratified random sampling method. They were interviewed and their blood pressure
      measured along with other anthropometric variables. Hypertension was defined
      according to the Sixth Report of the Joint National Committee on prevention,
      detection, evaluation and treatment of high blood pressure (JNC-VI). RESULTS: The
      overall prevalence of hypertension was 33.3%. Among the patients with
      hypertension, 21.6% were aware of their illness. The determinants of hypertension
      were age, intake of extra salt in the diet, body mass index and waist-hip ratio
      (derived by multiple logistic regression analysis with backward elimination of
      non-significant factors). Multivariate analysis showed that females had a higher
      risk of hypertension than males. CONCLUSION: The prevalence of hypertension in
      the native population of Assam is high. Implementation of an effective awareness
      programme with lifestyle modifications is necessary to control the cardiovascular
      disease burden in this population.

PMID- 15736550
TI  - Comparison of an immunochromatographic card test with night blood smear
      examination for detection of Wuchereria bancrofti microfilaria carriers.
AB  - BACKGROUND: At present, two diagnostic tests--Og4C3 ELISA and an
      immunochromatographic card test (ICT)--are available to detect circulating
      filarial antigens of Wuchereria bancrofti in serum/whole blood samples collected
      during the day. We aimed to assess the sensitivity of the new format card test
      'NOW ICT Filariasis' in detecting microfilaria carriers of W. bancrofti in
      comparison with conventional microscopic techniques and Og4C3 ELISA. METHODS: A
      total of 200 persons were selected from two villages following a quota sampling
      design (100 in each village). The required number of houses was selected using a
      systematic sampling procedure with a random start of the first household. Blood
      samples were taken from all the available persons in each selected house until
      the quota of 100 was reached. The new format ICT test, Og4C3 ELISA and night
      blood smear examination for microfilaria were carried out following standard
      procedures. RESULTS: The sensitivity of the new format ICT test was 100% among
      microfilaria carriers (detected by both early and late readings). The kappa
      statistic measure of agreement between the two readings of all the samples (n
      =200) tested was 0.811 (p<0.05). The new format test also reported 25% of
      microfilaria-negative individuals as being positive for circulating filarial
      antigens. However, the diagnostic lines were not stable beyond 10 minutes
      (particularly in the case of amicrofilaraemic persons). Though there was an
      overall agreement between the results of ICT and Og4C3 tests (kappa =0.612; p<
      0.05), the sensitivity of the Og4C3 test was lower than that of ICT. CONCLUSION:
      The new format ICT test is highly sensitive in detecting microfilaria carriers in
      endemic communities. Improvement in the format to provide stable diagnostic
      lines, specificity of the format and cost of the test kit are to be considered
      before its large-scale use.

PMID- 15736551
TI  - Clinical and echocardiographic findings in patients with myocardial toxicity due
      to scorpion sting.
AB  - BACKGROUND: Myocardial toxicity following a sting by the Indian red scorpion
      (Mesobuthus tamulus) is a life-threatening medical emergency. A perusal of the
      published literature suggests that this problem has seldom been studied
      systematically. METHODS: We retrospectively studied the clinical presentation and
      echocardiographic findings in 24 patients (mean [SD] age 23.2 [11.7] years; 19
      males) with myocardial toxicity caused by the sting of an Indian red scorpion
      (Mesobuthus tamulus). They were treated with inotropic support and diuretics
      depending on the requirement. At admission, oral L-carnitine was administered in
      a dose of 1980 mg/day in three divided doses till the left ventricular (LV)
      function normalized. None of the patients received digitalis, prazosin,
      hydrocortisone or antivenin. RESULTS: Extreme anxiety and severe pain at the site
      of sting were present in all the patients. Hypotension (n = 19), pulmonary oedema
      (n= 15) and acute renal failure (n=8) were the other presenting features. Chest X
      ray revealed cardiomegaly in 8 and pulmonary oedema in 13 patients. Serum
      creatinine phosphokinase levels were elevated more than two times the upper limit
      of normal (200 IU/L) in 22 patients (92%). The mean duration of hospitalization
      was 5 days (range 3- 11 days). L-carnitine treatment resulted in significant
      reduction in the LV diameter (mm) in diastole (47.6 [6.2] v. 42 [6.1], p < 0.01)
      and systole (42 [7.1] v. 28.2 [4], p<0.001); end-diastolic volume (ml) (108.7
      [31.9] v. 81 [26.7], p <0.01) and end-systolic volume (ml) (81.3 [30.9] v. 31.1
      [10.7], p < 0.001); and significant improvement in the stroke volume (ml) 27.8
      [13.2] v. 61.7 [6.2], p<0.001) and ejection fraction (%) (25.5 [12.8] v. 61.2
      [6.5], p<0.001). All the patients responded well to treatment and none died.
      CONCLUSION: Our initial observations suggest a potential benefit with additional
      oral L-carnitine treatment in patients with myocardial toxicity caused by
      scorpion sting presenting with hypotension and severe LV dysfunction. These
      findings merit further study.

PMID- 15736552
TI  - Changing patterns of sexually transmitted infections in India.
AB  - Sexually transmitted infections (STIs) are more dynamic than other diseases
      prevailing in the community. Their epidemiological profile varies from country to
      country and from one region to another within a country, depending upon
      ethnographic, demographic, socioeconomic and health factors. The clinical pattern
      is also a result of the interaction among pathogens, the behaviours that transmit
      them and the effectiveness of preventive and control interventions. We reviewed
      the changing patterns of different STIs (excluding HIV infection) in India and
      their various risk factors. A MEDLINE search was undertaken using the key words
      'sexually transmitted infections, epidemiology, India'. Related articles were
      also searched. In addition, a manual search for many Indian articles, published
      in journals that are not indexed was also carried out. Wherever possible, the
      full article was reviewed. If the full article could not be traced, the abstract
      was used. Most of the published data are institution based. There is a paucity of
      community-based data, except for information obtained from high risk groups such
      as commercial sex workers, truck drivers, hotel workers and drug abusers. From
      the literature search undertaken, it was observed that during the 1960s and
      1970s, bacterial infections including syphilis, chancroid and gonorrhoea were the
      major STIs, while viral infections caused by herpes simplex virus and human
      papillomavirus were so rare that they merited publication as case reports. Since
      the 1980s, the spread of human immunodeficiency virus (HIV) with subsequent
      behavioural (sexual and healthcare) change, the indiscriminate and prophylactic
      use of over-the-counter broad-spectrum antibiotics, upgradation of health
      services at the primary level and the success of 'syndromic' approach of
      treatment, has resulted in major changes in epidemiological patterns. As in
      developed countries, there has been a rise in viral and chlamydial infections and
      a relative fall in the incidence of traditional infections. This has forced a
      reappraisal of the importance of sexual and healthcare behaviours, since the
      control of incurable viral STIs depends to a great extent on societal efforts at
      primary prevention and counselling rather than their early diagnosis and
      treatment, which is an effective strategy against curable bacterial STIs.

PMID- 15736553
TI  - Lead intoxication in children: a global concern.

PMID- 15736554
TI  - Polymerase chain reaction for the diagnosis of tuberculous pleural effusion.

PMID- 15736555
TI  - Positron emission tomography: is it a better way to detect metastases?

PMID- 15736556
TI  - A simple protocol to manage patients with unexplained somatic symptoms in medical
      practice.

PMID- 15736557
TI  - Kidneys for breakfast!

PMID- 15736558
TI  - Second opinions and related topics.

PMID- 15736559
TI  - Re-organizing the health services in Scotland.

PMID- 15736560
TI  - Physicians and presidential politics.

PMID- 15736561
TI  - Shortcomings of the Prenatal Diagnostic Techniques Act, 1994.

PMID- 15736562
TI  - Fibrillary glomerulonephritis in acute myeloid leukaemia.

PMID- 15736563
TI  - Current aspects of mitral valve surgery.

PMID- 15736564
TI  - Indications for mitral valve surgery.
AB  - The current indications for mitral valve surgery are summarized in this review.
      Remarkable advancements in surgical technique and in our ability to define the
      onset of ventricular dysfunction have led to increasingly liberal indications for
      mitral valve surgery. Mitral valve repair for mitral regurgitation (MR) might be
      employed in asymptomatic patients with normal left ventricular function if valve
      repair were almost certain while in patients with severe left ventricular
      dysfunction, where valve replacement with destruction of the valve apparatus is
      most unwise, successful repair can lead to an improved quality of life. However,
      much is left to be done: increased repair rate, better definition of the role of
      surgery in both ischemic and myopathic MR and the role of limited incision
      surgery are all on the exciting horizon of the future.

PMID- 15736565
TI  - The role of annuloplasty in mitral valve repair.
AB  - Mitral valve repair surgery has progressed dramatically since its inception over
      40 years ago. As techniques have evolved, complicated mitral valve reconstruction
      has become commonplace, with durable late results. Likewise, the value of
      concomitant annuloplasty during valve repair has been firmly established as
      contributing to late valve repair durability. This review discusses the evolution
      of annuloplasty techniques and the physiologic reasoning behind various
      approaches.

PMID- 15736566
TI  - Long-term performance of prostheses in mitral valve replacement.
AB  - The long-term performance of prostheses in mitral valve replacement (MVR) is now
      available with representatives of current generation prostheses to 15 years.
      Mechanical prostheses have been implanted for 33 years and bioprostheses for 22
      years. The predominant complication of mechanical prostheses is hemorrhage from
      anticoagulation and reoperation for late structural valve deterioration of
      bioprostheses. Mitral valve (MV) reconstruction, over MVR, is recommended
      whenever possible, especially with the advancement of atrial fibrillation
      ablation techniques. The current indications for MVR are those valvular lesions
      that are unlikely to be repaired by most surgeons or which long-term results are
      suboptimal with reconstruction. Reconstruction is more common for degenerative
      disease, replacement for rheumatic disease and variable for advanced ischemic and
      infective disease. The recommendations for MVR for mitral stenosis (MS) are
      moderate to severe MS with advanced functional status and severe pulmonary
      hypertension when percutaneous balloon valvotomy or mitral reconstruction is not
      feasible. MVR is recommended in non-ischemic severe mitral regurgitation (MR) and
      for non-reparable acute symptomatic MR, advanced symptomatic status, systolic
      dysfunction and/or ventricular dysfunction. The recommendations for MV surgery in
      ischemic MR are acute post-infarction MR with cardiogenic shock, unstable angina
      with persistent moderate-severe and severe MR and chronic, dilated ischemic
      cardiomyopathy with moderate-severe and severe MR.

PMID- 15736567
TI  - Long-term results of bioprosthetic mitral valve replacement: the pericardial
      perspective.
AB  - Pericardial valve bioprostheses were introduced in early 1970s and were widely
      used in the 1980s. The longterm results with the Ionescu-Shiley valve, the first
      commercially available pericardial valve, were disappointing because of high rate
      cusp tears during the first decade after implantation. The enthusiasm for this
      type of bioprosthetic valve was further hampered by the premature failure of the
      Hancock pericardial valve. The long-term results of aortic valve replacement with
      the Carpentier-Edwards pericardial valve, which was introduced in 1981, indicated
      that that valve was durable and the issue of cusp tears had been resolved by an
      appropriate design. This knowledge prompted surgeons to revisit the merits of
      pericardial valves for mitral valve replacement and several other pericardial
      valves are now commercially available. The largest data on long-term results are
      with the Carpentier-Edwards pericardial mitral valve. The reported freedom from
      structure valve failure ranged from 69% to 85% at 10 years in patient population
      with mean age of 60 to 70 years. Young age is a major determinant of valve
      failure, which is largely due to calcification. There are also long-term data,
      albeit more limited on the Sorin Pericarbon and Mitroflow valves used for mitral
      valve replacement. This paper review the published experience with various
      pericardial bioprosthetic valves used for mitral valve replacement during the
      past 3 decades.

PMID- 15736568
TI  - Homologous transplantation of the mitral valve: a review.
AB  - Numerous experimental studies were conducted on homologous transplantation of the
      mitral valve either for mitral or tricuspid valve replacement in the early '60s.
      The first mitral homograft in humans was performed in 1965 by Senning. Since that
      time, there has been a limited number of implants mainly because of technical
      difficulties related to the insertion of the papillary muscles. Based on
      principles established for mitral valve repair, a reproducible method of
      homograft replacement of the mitral valve was described. Following validation in
      animals, the technique was applied in a series of 104 patients undergoing partial
      or complete mitral valve replacement. Significant improvements concerned:
      selection of indications and contraindications, staged approach according to the
      extent of the lesions leading either to partial or total replacement, systematic
      use of prosthetic ring annuloplasty, understanding of papillary muscle anatomy
      allowing a rationale for a reliable attachment method. In hospital mortality was
      3.8%. At 8 years, the incidences of patients free from cardiac death and from all
      death were 90.6% and 82% respectively. Freedom from any cardiac event (death or
      reoperation) was 72% at 7 years. Similarly to the aortic homograft, mitral
      homograft durability was decreased in younger patients. Partial homograft
      replacementoffered satisfactory results particularly in the case of endocarditis
      and enhanced the possibilities of valve repair. The limitations of the technique
      are: the technical difficulty which does not permit a completely standardized
      operation, the risk of early valve dysfunction related to valve mismatch and the
      risk of late deterioration mainly leading to stenosis. Homologous transplantation
      of the mitral valve was also applied for tricuspid valve replacement in the case
      of infective endocarditis or for replacement of a degenerated bioprosthesis.
      Satisfactory results have been reported. However due to the lack of anatomical
      landmarks, the implantation procedure has remained technically challenging. Thus
      until further progress demonstrates a clear superiority of the mitral homograft,
      bioprosthesis remains the gold standard for replacing the mitral or the tricuspid
      valve with a biological substitute.

PMID- 15736569
TI  - Surgery of congenital mitral valve disease.
AB  - Congenital malformations of the mitral valve are numerous and can be confusing.
      The functional expression is an insufficiency, a stenosis or a combined lesion.
      The anatomic classification is replaced by a functional approach. Anatomy and
      functional manifestations are analyzed by echocardiography pre-, intra- and
      postoperatively. Conservative surgery is the goal but is not always possible.
      Surgery of mitral valve insufficiency has a better prognosis than stenosis. The
      most difficult malformations are parachute and hammock mitral valves. When the
      mitral lesion is associated with another cardiac defect, the trend is to treat
      all the lesions in the same operation.

PMID- 15736570
TI  - Mitral valve surgery in non-ischemic cardiomyopathy.
AB  - Dilated cardiomyopathy is a disorder of the cardiac muscle in which myocyte
      cytoskeletal weakness leads to ventricular dilatation and congestive cardiac
      failure. Most commonly, the etiology of non-ischemic cardiomyopathy is unknown
      (idiopathic) and, in our practice, the second most common cause is advanced
      valvular heart disease. Functional mitral valve regurgitation occurs in up to 40%
      of patients with heart failure due to dilated cardiomyopathy and contributes to a
      vicious cycle of volume overload, further left ventricular dilatation, and
      worsening mitral valve regurgitation and heart failure. Surgical management of
      mitral valve regurgitation in dilated cardiomyopathy may carry a high risk and
      can be very challenging. However, operative risk is mitigated by continued
      vigorous medical management and judicious perioperative care. For example, at our
      Clinic, mortality for mitral valve repair or replacement in 43 patients with non
      ischemic cardiomyopathy having operation between 1993 and 2002 was 2.3%.
      Additional procedures to reverse cardiac remodeling have not proven to be
      uniformly successful and continue to undergo scientific scrutiny. Clinical
      outcome of mitral valve surgery in non-ischemic dilated cardiomyopathy compares
      well with cardiac transplantation in the early-to-intermediate term, but the long
      term results are less satisfactory. For our patients having mitral valve repair,
      the 1-, 3-, and 5-year survivorships were 84%, 80% and 33%. Evolving technology
      and research that focus on methods of altering or reversing cardiomyopathy; e.g.,
      cell transplant, may have significant impact on the future management of this
      debilitating illness.

PMID- 15736571
TI  - Minimally invasive mitral valve surgery.
AB  - Minimally invasive mitral valve surgery (MIC-MVS) was introduced into clinical
      practice in the mid 1990s. Since then it has evolved as the standard technique at
      some specialized centers. The routine technique includes femoral access for
      extracorporeal circulation, a right lateral minithoracotomy and direct aortic
      clamping using special instruments. Different techniques leading to some
      variations have been described. There is no prospectively randomized trial
      comparing minimally invasive with conventional mitral valve surgery. However,
      several series including large patient numbers and up to 8 years of follow-up
      have been published. Literature results as well as different aspects of minimally
      invasive MVS are discussed in this review, including the development, the current
      technique and future perspectives. Regarding MIC-MVS the word is that it is a
      safe and effective operation. Lateral minithoracotomy access offers excellent
      exposure, visualization can be further enhanced when using endoscopic cameras.
      All different mitral valve repair procedures can be performed even in the
      presence of complex pathologies. The repair rate is excellent and reaches 75%.
      Patient recovery is fast leading to a significant improvement in individual
      quality of life. MIC-MVS can now be considered the standard approach and will
      reach more widespread clinical application.

PMID- 15736572
TI  - An angiogenesis inhibitor TNP-470 (AGM-1470) suppresses vascular smooth muscle
      cell proliferation in experimental rat aortotomy models.
AB  - AIM: Vascular intimal hyperplasia is an important clinical concern in vascular
      diseases, such as anastomotic stricture as a possible complication of
      cardiovascular surgery. We recently suggested that a rat aortotomy model could be
      substituted for a vascular anastomotic stricture around a suture line. TNP-470 is
      known as an angiogenesis inhibitor and has demonstrated abilities to inhibit DNA
      synthesis of smooth muscle cells (SMCs) and SMCs proliferation. The aim of this
      study was to investigate the effect of TNP-470 on SMC proliferation using rat
      aortotomy models. METHODS: Longitudinal aortotomy was performed in the abdominal
      aorta of rats. Rats received a subcutaneous injection of materials (TNP-470, 20
      mg/kg) or vehicle 3 times a week (n=10 in each group). The aorta was harvested 2
      weeks after aortotomy. Serial sections from tissues were stained with hematoxylin
      and eosin, and the ratio of intimal to medial cross-sectional areas (I/M ratio)
      was determined. Values are expressed as the mean +/- the standard deviation.
      Results. Thickening of the intimal layer 2 weeks following aortotomy was observed
      in the control group however, intimal thickening was inhibited in the TNP-treated
      group. The I/M ratio was significantly (p = 0.0376) lower in the TNP-treated
      group than in the control group (8.3 +/- 4.8 vs 15.6 +/- 9.6%). Conclusion. TNP
      470 significantly suppressed intimal thickening in experimental rat aortotomy
      models. TNP-470 might inhibit the development of anastomotic stricture after
      cardiovascular surgery.

PMID- 15736573
TI  - Abdominal aortic aneurysm repair in a patient with a congenital solitary pelvic
      kidney. A case report.
AB  - Abdominal aortic aneurysm (AAA) is rarely associated witha congenital pelvic
      kidney. To date only 11 cases have been reported in the literature in which a
      solitary pelvic' kidney was associated in only 1 patient. Repair of thesaneurysm
      is technically demanding because the abnormal origin of the renal arteries
      presents the problem of renal ischemia duringaortic cross-clamping. We report a
      case of a 77-year-old man who was found to have an AAA associated with a
      congenital solitary pelvic kidney. An abdominal aortography dearly showed 2
      aberrant renal arteries, one of which originated from the aortic wall just above
      the aortic bifurcation and the other from the left common iliac artery. At
      surgery, we found other associated anomalies including malrotation of the gut and
      a left undescended testis. The surgical procedure consisted of an
      aneurysmorrhaphy followed by a tube graft replacement with therenal arteries
      being left intact to the distal aortic wall or below. Renal preservation during
      aortic cross-clamping was achieved by direct perfusion of the upper renal artery
      with cold lactated Ringer's solution together with topical cooling with ice
      slush. The patient's postoperative course was uneventful. Urinary output was
      satisfactory and serum creatinine level remained unchanged throughout his
      hospital stay. The renal preservation method used in this case was simple and
      effective.

PMID- 15736574
TI  - Surgical treatment of abdominal aortic aneurysm associated with horseshoe kidney
      and coagulopathy case report.
AB  - The coexistence of horseshoe kidney and aortic aneurysm poses a technical
      challenge to the vascular surgeon during aneurysm repair. Whether to divide the
      renal isthmus and how to approach the aneurysm are still matters of controversy,
      and coagulopathy sometimes occurs in patients with nontreated abdominal aortic
      aneurysm (AAA). We describe the successful surgical repair of an AAA with
      horseshoe kidney via the transperitoneal approach and division of the renal
      isthmus by harmonic scalpel. Exclusion of a thrombosed aneurysm can ameliorate
      coagulopathy due to AAA.

PMID- 15736575
TI  - Life threatening chronic expanding hematoma of the thorax.
AB  - A 73-year-old man presented with severe respiratory distress and systemic edema.
      Diagnosis of chronic expanding hematoma (CEH) was made through examination of
      past and present radiographic studies. A giant mass lesion with surrounding
      calcification occupying the left hemi-thorax on the chest was demonstrated via
      computed tomography on admission, and a chest X-ray from 8 years previously
      revealed evidence of tubercular pleurisy. The patient's condition deteriorated
      rapidly after admission, necessitating urgent operative resection of the mass.
      The mass consisted of fresh and organized blood and demonstrated a calcified
      fibrous capsule, findings that are consistent with the diagnosis of CEH. Although
      the patient's condition improved following operative removal of the mass, he was
      ultimately diagnosed with postoperative empyema secondary to bronchopleural
      fistula, necessitating additional surgery.

PMID- 15736576
TI  - Emergent pneumonectomy for hemoptysis in a patient with previous thoracoplasty.
AB  - Hemoptysis is a life-threatening episode of respiratory disease. By means of
      every possible treatment, hemostasis should be obtained to secure the airway as
      well as to prevent blood loss. We describe an emergent pneumonectomy for massive
      hemoptysis from destroyed lung in a patient with previous thoracoplasty. After
      prolonged ventilation support postoperatively, the patient with compromised lung
      function recovered well.

PMID- 15736577
TI  - Prevention of sudden death in mitral valve prolapse.

PMID- 15736578
TI  - Infection of the post-pneumonectomy space after dental procedures.

PMID- 15736579
TI  - Concurrent type a aortic dissection and lung abscess mimicking
      aortobronchopulmonary fistula.

PMID- 15736580
TI  - Tracheal carcinoid during pregnancy.

PMID- 15736581
TI  - Congenital cystic adenomatoid malformation of the lung (CCAM) in children.
      Indications to early treatment in asymptomatic patients.

PMID- 15736582
TI  - Biology of the troponin complex in cardiac myocytes.
AB  - Troponin is the regulatory complex of the myofibrillar thin filament that plays a
      critical role in regulating excitation-contraction coupling in the heart.
      Troponin is composed of three distinct gene products: troponin C (cTnC), the 18
      kD Ca(2+)-binding subunit; troponin I (cTnI), the approximately 23-kD inhibitory
      subunit that prevents contraction in the absence of Ca2+ binding to cTnC; and
      troponin T (cTnT), the approximately 35-kD subunit that attaches troponin to
      tropomyosin (Tm) and to the myofibrillar thin filament. Over the past 45 years,
      extensive biochemical, biophysical, and structural studies have helped to
      elucidate the molecular basis of troponin function and thin filament activation
      in the heart. At the onset of systole, Ca2+ binds to the N-terminal Ca2+ binding
      site of cTnC initiating a conformational change in cTnC, which catalyzes protein
      protein associations activating the myofibrillar thin filament. Thin filament
      activation in turn facilitates crossbridge cycling, myofibrillar activation, and
      contraction of the heart. The intrinsic length-tension properties of cardiac
      myocytes as well as the Frank-Starling properties of the intact heart are
      mediated primarily through Ca(2+)-responsive thin filament activation. cTnC,
      cTnI, and cTnT are encoded by distinct single-copy genes in the human genome,
      each of which is expressed in a unique cardiac-restricted developmentally
      regulated fashion. Elucidation of the transcriptional programs that regulate
      troponin transcription and gene expression has provided insights into the
      molecular mechanisms that regulate and coordinate cardiac myocyte differentiation
      and provided unanticipated insights into the pathogenesis of cardiac hypertrophy.
      Autosomal dominant mutations in cTnI and cTnT have been identified and are
      associated with familial hypertrophic and restrictive cardiomyopathies.

PMID- 15736583
TI  - Troponins in acute coronary syndromes.
AB  - Cardiac troponins have replaced creatine kinase-MB as the preferred biomarker for
      establishing the diagnosis of myocardial infarction (MI). Expert recommendations
      set the diagnostic decision-limit for each assay at the 99th percentile of
      troponin levels in an apparently healthy reference population, which due to a
      lack of standardization, will vary depending upon the manufacturer. Among
      patients presenting with an acute coronary syndrome (ACS), even low-level
      elevations of cardiac troponin T or I correlate with higher risk of death and
      recurrent ischemic events compared to patients with levels of troponin below the
      decision limit. Renal failure does not appear to diminish the prognostic value of
      troponins among patients with a high clinical probability of ACS. Moreover,
      patients with elevated levels of troponin derive the most benefit from more
      intense medical therapy with antithrombin and antiplatelet medications, as well
      as an early invasive management strategy. Whereas cardiac troponins are extremely
      specific for myocardial necrosis, they do not discriminate between ischemic and
      non-ischemic etiologies of myocardial injury. Clinicians must, therefore,
      determine whether a patient's presenting symptoms are consistent with ACS.
      Combining troponin with other cardiac biomarkers may offer complimentary
      information on the underlying pathobiology and prognosis in an individual
      patient. Future generations of troponin assays may detect specific
      posttranslational modifications of troponins that may increase the analytic
      sensitivity for myocardial damage and offer insight into the timing and mechanism
      of myocardial injury.

PMID- 15736584
TI  - Analytical issues for cardiac troponin.

PMID- 15736585
TI  - Cardiac troponins in renal insufficiency and other non-ischemic cardiac
      conditions.
AB  - The emergence of cardiac troponins has been an interesting step in the diagnosis
      of ACS. It has clearly helped us to better triage patients toward a more
      aggressive posture in performing early cardiac catheterization, and in some
      cases, early use of adjunctive Gp IIb/IIIa antagonists and percutaneous or
      surgical myocardial revascularization. However, with this step forward has come
      uncertainty and many cardiology consults regarding positive cardiac troponins in
      patients without ACS or myocardial infarction. In general, increased cardiac
      troponins imply a worse prognosis. This is clearly true of patients with ESRD and
      advanced heart failure. It is also true of patients with severe, noncardiac
      illnesses. In other situations, such as acute pericarditis and cardiac surgery,
      slightly elevated cardiac troponins do not seem to predict a worse prognosis, and
      can probably be disregarded. The elevation of cardiac troponins after successful
      percutaneous coronary interventions is not unexpected, and the level of cardiac
      troponin release seems to predict problems, but lively controversy persists.
      Last, monitoring cardiac troponins in cardiac transplant recipients and those
      receiving certain cardiotoxic chemotherapies may be of some diagnostic value, but
      clearly more experience and clinical research are needed.

PMID- 15736586
TI  - Developing the next generation of cardiac markers: disease-induced modifications
      of troponin I.
AB  - Troponin I (TnI) and Troponin T (TnT) have evolved into arguably the two most
      important diagnostic markers for acute myocardial injury. Part of their
      diagnostic utility lies in the uniquely important roles that both TnI and TnT
      play in the calcium-dependent regulation of cardiac muscle contraction. Both
      proteins undergo extensive physiologic regulation, principally through
      phosphorylation, as well as specific disease-induced pathologic modifications,
      including phosphorylation, oxidation, and proteolysis. Many, if not all, of these
      protein modifications in some way modulate contractility, and when detected in
      serum may therefore provide important information about both the disease state
      and functional status of the heart. However, the complexity of the TnI (and TnT)
      forms in the serum is large, which leads to difficulty in detecting all of the Tn
      subunits in serum, and hence interpreting the biologic significance of each
      modified product. But, as diagnostic tools and modalities improve, our ability to
      monitor and detect specific disease-induced modified forms of proteins will
      inevitably lead to better and more specific diagnoses and therapies.

PMID- 15736587
TI  - Constitution aims to bring an end to health economy warfare.
AB  - A rough new constitution is being drawn up for the NHS in a bid to prevent health
      economies sliding into bitter 'Bradford-style' warfare in the era of foundations
      trusts and payment by results. The rules of engagement are part of a package of
      measures designed to rescue some of the government's flagship reforms amid
      warnings from audit chiefs on the impact of PbR.

PMID- 15736588
TI  - Evercare says pilots would do better with own staff.
AB  - The company behind the Evercare model of chronic-disease management has claimed
      that it could cut admission rates far more dramatically than NHS pilots have done
      so far if it hired its own nurses. The claim, from UnitedHealth Europe's Dr
      Richard Smith, comes in the wake of research which found that the 10 English
      pilots had cut admissions by less than 1 per cent.

PMID- 15736589
TI  - Over 2,000 face Hep C scare.

PMID- 15736590
TI  - Foundation trusts. Bradford: how the trust and the regulator finally fell out.
AB  - Foundation regulator Bill Moyes gradually lost confidence in recovery plans put
      forward by Bradford Teaching Hospitals trust in a series of meetings last
      November and December. Papers released under the Freedom of Information Act show
      it accused the trust of not taking 'timely or appropriate action' to resolve the
      crisis, and not settling disputes with local PCTs.

PMID- 15736591
TI  - On integrating social care.

PMID- 15736592
TI  - The prophet motive. Interview by Mary-Louise Harding.
AB  - Bradford Teaching Hospitals trust's crisis shows how even 'one of the best
      organisations in the old regime' could be 'suddenly overwhelmed', says Audit
      Commission chief executive Steve Bundred (pictured). He warns that the 2008
      deadline for all trusts to be foundations is 'still achievable, but only if the
      sector raises its game on the quality of financial management and available
      data'. He also highlights the costing for the consultant contract as an area
      where 'the government may need to look again'.

PMID- 15736593
TI  - Data briefing. Why length-of-stay link is so vital.

PMID- 15736594
TI  - Practice-based commissioning special. A new show in town.
AB  - From April 1, practice-based commissioning will be operational; meaning practices
      can request indicative budgets from PCTs. Practices should be incentivised to
      take on budget deficits. There are concerns that the role of practice-based
      commissioning as a counterweight to payment by results will reinforce divisions
      between acute and primary care.

PMID- 15736595
TI  - Contracting job.
AB  - Sixteen GP practices in Epsom Downs have formed an NHS limited company, bringing
      them together as one provider-contracting organisation. Practices and the PCT
      hope to use these new flexibilities together with practice-based commissioning to
      redesign local services. By pooling resources, the practices can treat more
      patients within primary care, keeping expenses low.

PMID- 15736596
TI  - Non-consultant contract. Career-grade progression.

PMID- 15736597
TI  - Recruiting clinicians. Foreign legion.

PMID- 15736598
TI  - Diversity. Crossing the pink plateau.

PMID- 15736599
TI  - Management of cardiac devices as the end nears.

PMID- 15736600
TI  - Terminal care...not terminal career.

PMID- 15736601
TI  - On Kubler-Ross: is there a sixth stage of dying?

PMID- 15736602
TI  - Pacemaker and defibrillator deactivation in competent hospice patients: an
      ethical consideration.
AB  - The Denver Community Bioethics Committee (DCBC) is an independent, community
      based group that undertakes ethics consultations for any individual or
      organization. Its members include adult protection professionals, physicians,
      elder-law attorneys, chaplains, nurses, social workers, and lay persons. In its
      11-year history, the Committee has heard numerous cases concerning end-of-life
      care, futile treatment, and patients' rights. In 2003, a Colorado hospice
      provider asked the DCBC for assistance in developing a policy on deactivation of
      pacemakers and defibrillators in competent hospice patients. The hospice had
      encountered concerns from some physicians and cardiac care clinicians that
      deactivating such devices treads the fine line between legitimate withdrawal of
      burdensome treatment and assisted death. Although the specific deliberations of
      the DCBC are confidential, this article summarizes contributions from the
      committee's discussion, as well as independent research undertaken by the author.

PMID- 15736603
TI  - Cardiopulmonary resuscitation is not addressed in the admitting medical records
      for the majority of patients who undergo CPR in the hospital.
AB  - Cardiopulmonary resuscitation (CPR) is routinely performed on patients who
      develop cardiopulmonary arrest in the hospital. In some situations, it is
      performed on terminally or critically ill patients where death is predicted to be
      inevitable despite CPR. Since prior consent is not required for this procedure,
      CPR may be performed without patient consent or foreknowledge. Many of these
      patients may not want CPR if the anticipated outcome is reviewed with them. This
      study investigated the frequency of occurrence of a CPR discussion at the time of
      hospital admission for patients who undergo CPR during hospitalization. Results
      showed that CPR is infrequently addressed in the hospital orders or medical
      records in patients who undergo CPR during their hospital stay. In addition, the
      severity of illness at the time of admission does not appear to influence whether
      physicians discuss CPR with patients and their families.

PMID- 15736604
TI  - End-of-life care: perspectives of family members of deceased patients.
AB  - This study was undertaken to determine the opinions of family members of deceased
      patients regarding end-of-life care. This multisite cross-sectional survey was
      administered to 969 volunteer participants during 1997 to 2000. Eligible
      participants included immediate family members of deceased patients at five local
      institutions in a regional health system. Among 969 respondents, most (84.4
      percent) indicated that the care for their family member was excellent. Reasons
      cited for satisfaction included overall care (40.2 percent), staff effort (23.2
      percent), and communication (16.4 percent). Reasons cited for dissatisfaction
      included perceived incompetence (9.7 percent), perceived uncaring attitude (8.4
      percent), and perceived understaffing (3.7 percent). Respondents were more
      satisfied with communication from nursing staff (88 percent) than physicians'
      communication (78 percent, p < 0.001, Bowker's test). Respondents indicated
      higher overall satisfaction with nursing (90 percent) and pastoral care (87
      percent), than with physician care (81 percent, p < 0.001 and p = 0.006, Bowker's
      test). A unique survey instrument can be used to measure family perceptions and
      opinions regarding end-of-life care.

PMID- 15736605
TI  - Healthcare professional education: a unique role for hospices.
AB  - We sought to describe the educational experiences that hospices currently provide
      for students in health professions by using a national cross-sectional, Web-based
      survey of the National Hospice and Palliative Care Organization (NHPCO) and the
      Population-based Palliative Care Research Network (PoPCRN) hospice sites. Of the
      75 responding sites, 71 (95 percent) participated in the education of health
      profession students, most commonly providing education for bachelor of science in
      nursing students (73 percent), associate's degree nursing students (61 percent),
      master's-level social work or counseling students (61 percent), registered
      nursing students (59 percent), medical students (58 percent), and medical
      residents (57 percent). Significant staff time was devoted to educating these
      students (averaging 11 to 30 hours/week), but less than 3 percent received any
      financial compensation. Therefore, we conclude that hospices provide a
      significant amount of uncompensated education. This conclusion provides a unique
      opportunity for hospices to collaborate with healthcare educational institutions
      and to influence the work force of the future.

PMID- 15736606
TI  - Radiopharmaceuticals for the palliation of painful bone metastases.
AB  - Metastatic bone pain is prevalent in advanced cancer, and, despite a plethora of
      available therapies, effective palliation remains a clinical challenge. Bone
      seeking radiopharmaceuticals are an often-overlooked but valuable analgesic
      option for select patients. These agents work by binding to hydroxyapatite at the
      tumor-bone interface of osteoblastic lesions, delivering therapeutic doses of
      radiation to closely circumscribed tissue regions. They have been shown to reduce
      pain and improve quality of life. Their safety, simplicity, convenience of
      administration, and cost-effectiveness make them suitable for hospice and
      palliative care settings.

PMID- 15736607
TI  - The use of motion sickness bands to control nausea and vomiting in a group of
      hospice patients.
AB  - OBJECTIVE: To explore the potential benefits of using motion sickness bands
      (MSBs) to control nausea and vomiting in a hospice-based patient population.
      METHODS: A nonblinded, yearlong observational study. RESULTS: From February 2003
      to February 2004, 33 patients entered into the study. The mean age of the study
      cohort was 67 years, with a predominance of females to males and cancer as the
      most common admitting diagnosis. Twenty-nine of the 33 patients studied showed a
      positive response to the intervention for a response rate of 88 percent.
      CONCLUSIONS: MSBs demonstrated efficacy in controlling nausea and vomiting in a
      group of hospice patients. Added benefits of patient empowerment and financial
      savings also were noted. Further study is warranted.

PMID- 15736608
TI  - Modafinil to treat fatigue in amyotrophic lateral sclerosis: an open label pilot
      study.
AB  - An open label trial of modafinil was conducted to determine whether it would be
      tolerated and effective in treating fatigue for people with amyotrophic lateral
      sclerosis (ALS). Fifteen patients with ALS were treated for two weeks with either
      200 mg or 400 mg of modafinil. Reported side effects of the medication were mild
      and included diarrhea, headache, nervousness, and insomnia. Side effects did not
      result in any study dropouts. Following treatment, mean scores on the Fatigue
      Severity Scale (FSS) decreased from 51.3 (SD 9.2) to 42.8 (SD 10.2). On the
      Epworth Sleepiness Scale (ESS), mean scores decreased from 8.2 (SD 2.0) to 4.5
      (SD 2.4). Reductions in both the FSS and the ESS were significant at p < 0.001.
      Mean scores on the self-report version of the Functional Independence Measure
      (FIM-SR) increased from 115.2 (SD 5.6) to 118.1 (SD 5.4), with p < 0.01. This
      pilot study suggests that modafinil is well-tolerated and may reduce symptoms of
      fatigue in ALS. Further blinded, controlled studies of modafinil in larger
      numbers of ALS patients are warranted.

PMID- 15736609
TI  - Sisters to the end: the rights of the mentally retarded to refuse treatment.

PMID- 15736610
TI  - Six steps to innovation.

PMID- 15736611
TI  - Challenges of mentoring a brain-injured peer.

PMID- 15736612
TI  - Implications of advances in human genetics for rehabilitation nursing.

PMID- 15736613
TI  - How do we handle conflicts with parents over unsafe oral feedings?

PMID- 15736614
TI  - Modification of bed systems and use of accessories to reduce the risk of hospital
      bed entrapment.
AB  - Despite the long history of hospital-bed use, only in the past decade have bed
      related patient-safety hazards, including falls and life-threatening entrapment,
      been discussed publicly. Entrapment is an event in which a patient is caught,
      trapped, or entangled in hospital-bed components, including the bed rail,
      mattress, or hospital-bed frame. Since 1995, the Food and Drug Administration and
      the Joint Commission on Accreditation of Healthcare Organizations have issued
      patient-safety alerts about entrapment. While new beds are being manufactured
      without large gaps that would allow an individual's head, neck, or chest to
      become entrapped, it is incumbent upon healthcare providers, including
      rehabilitation nurses, to ensure the safety of older beds in use. This article
      describes a facility-based approach for identifying and managing risk related to
      hospital bed-entrapment to be used in rehabilitation settings.

PMID- 15736615
TI  - Analysis of the explanatory model of health promotion and QOL in chronic
      disabling conditions.
AB  - Until recently, persons with disabling conditions have not had adequate attention
      paid to their health promotion and disease prevention needs. This lack has
      resulted in a scarcity of relevant data on which to base effective healthcare
      practices. The Explanatory Model of Health Promotion and QOL in Chronic Disabling
      Conditions, by Stuifbergen and colleagues, is the result of years of research
      investigating the health-related needs and perspectives of the disabled
      population. This article explicates the model by reviewing its constituent
      origins and meanings. The model also is analyzed critically for logical adequacy,
      usefulness, generalizability, parsimony, and testability. Finally, the model is
      proposed as a sound framework to guide nursing practice and research.

PMID- 15736616
TI  - Social support in cyberspace: lessons learned.
AB  - The lessons learned from the implementation of phase one of Women to Women
      (WTW1), a research-based computer outreach program for rural women with chronic
      illness, and their influence on the development of phase two of Women to Women
      (WTW2) are discussed in this article. The changes implemented in WTW2 included
      moving from the FirstClass delivery platform to WebCT; increasing the intra- and
      interdisciplinary nature of the team by adding nurse experts in Web skills and
      women's health and non-nurse colleagues in family finance and nutrition;
      expanding the geographical area to be served from Montana to adjoining states;
      developing health teaching units that harness the internet as the major source of
      ever-current health information; including a control group in the study design;
      and selecting more pertinent, repeated measurement instruments to assess
      psychosocial variables.

PMID- 15736617
TI  - A study of spirituality and life satisfaction among persons with spinal cord
      injury.
AB  - The purpose of this study was to investigate the relationship of spirituality and
      life satisfaction among persons with spinal cord injury. A nationwide sample of
      230 persons with long-term spinal cord injury completed the Satisfaction With
      Life Scale (SWLS), the Quality of Life Index (QLI), and a demographic data form.
      Data analysis also indicated that there was a significant positive correlation
      between life satisfaction and psychological/spiritual factors of the QLI
      instrument. Nurses are mandated by the International Council of Nurses, the Joint
      Commission on Accreditation of Healthcare Organizations, and the Patient's Bill
      of Rights (Maddox, 2001) to provide spiritual care for clients. Rehabilitation
      nurses have the opportunity to support spirituality and life satisfaction as we
      assist our clients with disabilities to redefine their lives and explore new life
      opportunities.

PMID- 15736619
TI  - Indigenous peoples health in the Arctic.

PMID- 15736618
TI  - 35 years of ICCH: evolution or stagnation of circumpolar health research?
AB  - The first Circumpolar Health symposium took place in Fairbanks in 1967.
      Approximately every three years since, an increasing number of researchers have
      met to present and discuss the health conditions of the North. We analysed the
      proceedings from the 11 congresses and the abstracts from the 12th congress in
      2003 and found a shift of focus from biology to sociology of health. Today,
      circumpolar health research is primarily focused on three major topics: 1.
      epidemiology of indigenous peoples of the North; 2. health care delivery in the
      North; and 3. the effect of physical factors on human physiology and health.
      Despite the diverse research interests, it is remarkable how a community of
      circumpolar scientists and practitioners has emerged over the past 35 years.

PMID- 15736620
TI  - The challenge of reducing youth suicide in Greenland--interventions, strategies
      and roads to be explored.

PMID- 15736621
TI  - Viral hepatitis in the Arctic.
AB  - OBJECTIVES: Summarize research on viral hepatitis in indigenous populations in
      the Arctic. STUDY DESIGN: Literature review. METHODS: Medline search from 1966
      2003. RESULTS: High prevalence rates of total hepatitis A antibody of > 50% and
      of hepatitis B of between 22% in Alaska and 42% in Greenland for total infection
      and between 3% in Canada and 12% in Siberia for chronic infection have been
      reported. Universal childhood vaccination with hepatitis A vaccine beginning at
      age 2 have stopped epidemics of HAV in Alaska and newborn hepatitis B
      immunization programs in Alaska and Canada have reduced new infections. However,
      in all Arctic countries several thousand persons chronically infected with HBV
      remain at risk for the development of cirrhosis and hepatocellular carcinoma.
      Prevalence rates of hepatitis C (HCV) reported are <1.4% in the Arctic. Hepatitis
      D virus, which co-infects with HBV, has been found in 40% of persons with HBV in
      Greenland. CONCLUSIONS: High rates of viral hepatitis A, B, C, and D are found in
      the Arctic. Effective vaccines against HAV, HBV and HDV can prevent transmission
      of these viruses. In addition, new antiviral therapies for HBV and HCV can be
      used effectively to treat many chronically infected patients.

PMID- 15736622
TI  - Health care in the circumpolar world: Greenland.
AB  - Greenland is part of the Kingdom of Denmark and it is the world's largest island.
      An ice cap covers 85% of its territory. The population is about 57,000
      inhabitants, with 14,000 living in the capital Nuuk, and 10,000 in villages and
      other small settlements. There are pronounced regional variations in lifestyle
      and living conditions. The Greenland Home Rule Government assumed responsibility,
      for health care on 1 January 1992. Greenland's territory is divided into 16
      health care districts. Queen Ingrid's Hospital in Nuuk is the national hospital
      and has 156 beds and numerous specialist physicians associated with it. Each
      health district has a health care centre with one or more physicians, nurses and
      other health care personnel appropriate for the number of people living in the
      district. Each district health centre is responsible for primary health care in
      towns, villages and other small settlements, and the health centres treat all
      common illnesses. The health centres handle uncomplicated births, minor surgery,
      common treatment in internal medicine and community mental health services. The
      centres have a number of inpatient beds proportional to the number of people in
      the health district. People with more complicated illnesses are referred to Queen
      Ingrid's Hospital in Nuuk or to specialised treatment in Denmark.

PMID- 15736623
TI  - Health care delivery for Alaska Natives: a brief overview.
AB  - OBJECTIVES: Describe the Alaska Native Health Care delivery system and some of
      the historical elements that shaped it. STUDY DESIGN: Retrospective program
      review. METHODS: Retrospective review of existing administrative and clinical
      programs. RESULTS: Over the last 10,000-15,000 years the Alaska Native Health
      System developed from at traditional tribal based self-care system to a complex
      system that is interdependent on local, state, federal, and private insurance
      payers. The Alaska Tribal Health System takes an intentional approach to
      planning. While the system may face an uncertain future, it is poised to continue
      it remarkable success. The regional health corporations are the backbone of the
      system and it is the regional health corporations that own the Alaska Tribal
      Health System. In addition, it is the Alaska Tribal Health System that is
      responsive to the needs and priorities of the regional health corporations and
      their Native constituents. The spirit of the Alaska Native has inspired their
      health care providers at all levels to develop innovative "work arounds" to
      provide state of the art care through regionalization and telemedicine. Despite
      the many challenges ahead, the Alaska Tribal Health System will continue to
      strive to increase the health of Alaska Native people to the highest status
      possible. CONCLUSION: The Alaska Native health care system is a dynamic system
      administered by and for Alaska Native peoples. This system has risen to many
      challenges in the past and has made great strides through both ingenuity and
      necessity.

PMID- 15736624
TI  - Arctic telehealth: north to the future.
AB  - Over the past thirty years the delivery of health care services in Alaska has
      gone from Citizen Ban radio transmissions that were relayed through telephone
      bridges to one of the largest, state of the art telemedicine systems in the
      world. This transition has been marked by innovative approaches, learning from
      others, forged partnerships, open relationships with the telecommunication
      businesses, and a great deal of funding. This transition has required new
      approaches to health information, relinquishment of sole ownerships,
      collaboration, cooperation, and a unified voice. The system is not standalone.
      There are components that have influenced other endeavors. Health Aids now must
      be trained to make use of the electronic tools that they have at their remote
      clinics. Upgraded components for airborne medical evacuations need to match the
      overall system. Health professionals doing rotations and contracts in Alaska must
      learn how to interface with the telemedicine system. New administrators are being
      trained through a Master of Public Health program within the University of Alaska
      Anchorage that is taught entirely over the "Blackboard" computer-based system for
      distant delivery. The telehealth systems in Alaska and other Arctic nations are
      becoming the models to be replicated throughout the world. Excelsior.

PMID- 15736625
TI  - Body proportions in healthy adult Inuit in East Greenland in 1963.
AB  - OBJECTIVES: It is important to know the starting point when describing changes in
      Inuit in transition. STUDY DESIGN: The original charts of 1,852 individuals from
      the epidemiological investigation in East Greenland around 1963 performed by
      Littauer and colleagues were recovered recently. They included height, weight and
      a physical investigation. METHODS AND RESULTS: The focus of this paper was adult
      Inuit body proportions in 1963 by ten-year age groups excluding participants with
      disabilities affecting body build. Relatively stable values were seen in both
      genders with age. Median values in men/women aged 20 years and above were: height
      164/153.5 cm, weight 64/54 kg and BMI 23.7/23.1. Men aged 50 years and above had
      a little lower height and weight than young men. Women aged 40-49 years had a
      higher weight and BMI, but this evened out in the older age groups. Median BMI
      was relatively high compared to WHO definition. CONCLUSIONS: The data from 1963
      gives a starting point for evaluating changes in Inuit body build and the
      prevalence of overweight. Furthermore, they indicate a need for Inuit-specific
      normal BMI delineation.

PMID- 15736626
TI  - Obesity and metabolic correlates among the Inuit and a general Danish population.
AB  - OBJECTIVES: [corrected] Obesity and central fat pattern are associated with
      several cardiovascular risk factors incluy ding insulin resistance, glucose
      intolerance, hypertension and dyslipidemia in most populations. The study aims to
      assess the occurrence and metabolic correlates of obesity among Greenlanders and
      Danes. STUDY DESIGN: From 1999 to 2001, 917 adult Inuit participated in a health
      survey in Greenland. The examination included an oral glucose tolerance test.
      Body Mass Index, waist circumference, and blood pressure were measured. P
      glucose, s-insulin, and lipids were measured. Data from the Danish study
      'Inter99' (n=5606) conducted in 1999-2000 were used for comparison. RESULTS:
      Compared with the Inter99 population, a larger proportion of Inuit women were
      centrally obese (58.1% vs.17.8%, p<0.001) and central obesity was present in
      15.9% of Inuit men vs. 8.3% of the Danish men (p<0.001). At any given level of
      obesity the Inuit had lower levels of 2-hour glucose and insulin, blood pressure,
      triglyceride, and higher levels of HDL cholesterol than the Danish participants.
      Fasting glucose and fasting insulin levels within obesity categories were not
      different in the two populations. CONCLUSION: Central fat pattern and obesity are
      more prevalent among the Inuit, but the obesity observed among the Inuit is not
      associated with the same degree of metabolic disturbances as in a general Danish
      population.

PMID- 15736627
TI  - Mortality in the Kivalliq Region of Nunavut, 1987-1996.
AB  - INTRODUCTION: The Kivalliq region of Nunavut, Canada, had a 1996 population of
      7,131, of which 87% were Inuit. An attempt was made to characterize patterns of
      mortality in the region. STUDY DESIGN: Descriptive regional mortality study,
      based on 10-year retrospective review of health records data. METHODS: All deaths
      and stillbirths of Kivalliq residents during the study period were identified.
      Available health records data were reviewed for each death, including medical
      charts, death certificates and coroner's reports where applicable. Age
      standardized mortality rates, both overall and cause-specific, were calculated
      and compared to both Canadian national rates and territorial rates from the same
      time period. RESULTS: The infant mortality rate was 32.3/1,000 live births, five
      times Canada's rate. Leading causes of infant deaths were prematurity and Sudden
      Infant Death Syndrome (SIDS). The overall mortality rate was 1.8 times that of
      Canada, with leading causes of death being cancers (especially lung cancer),
      circulatory disease, respiratory disease, unintentional injury and suicide.
      CONCLUSIONS: Identified areas of concern included mortality due to premature
      birth, SIDS, unintentional injuries, suicides, respiratory disease and lung
      cancer. It is hoped that this study's results will assist territorial leaders,
      health workers and citizens in health planning activities.

PMID- 15736628
TI  - Burden of mortality in Greenland--today and tomorrow.
AB  - OBJECTIVES: Investigation of the relative impact of three factors expected to
      influence the future mortality burden in Greenland: demographic change,
      epidemiological transition and behavioural patterns. STUDY DESIGN: To identify
      general trends in public health status, evaluating the effect of public health
      campaigns and providing the basis for making predictions of future trends in the
      mortality burden data from the Greenlandic Death Causes Register to estimate
      Years of Life Lost (YLL) in the period 1976-1998 has been used. METHODS: YLL were
      estimated according to the Burden of Disease Method. Age standardised death rates
      were calculated per 10,000 person years. Regression analysis (ordinary least
      squares) using time as the explanatory variable was applied to project the time
      series 1976-1998 into the prediction period 1999-2028. RESULTS: The projections
      indicate that the demographic component in combination with behavioural patterns
      will have a dominant effect in the expected increase in the future burden of
      mortality. Relative to these two components, epidemiological transition will
      constitute a relatively insignificant impact on the future mortality burden in
      Greenland. CONCLUSION: Concerted multi-sectoral approaches and broad holistic
      health strategies related to health promotion and prevention today will
      strategically improve the capability of the Greenlandic society to manage the
      future disease burden from ageing via its health care sector and the
      institutional sector for care of the elderly.

PMID- 15736629
TI  - Health condition of Siberian population (medical ecological analysis).
AB  - OBJECTIVES: The aim of the investigation is to show, with the help of various
      scientific approaches, the Siberian population's state of health for the last
      years. METHOD: On the basis of results of a large cycle of population
      investigations of people in different zones of Siberia--shift workers,
      inhabitants of ecologically adverse regions, schoolchildren in sensitive periods
      of development--we discovered disorders of adaptive processes that are
      accompanied by a decrease of mental stability, readjustment of physiological
      regulation mechanisms and exhaustion of functional reserves of the organism.
      RESULTS AND CONCLUSIONS: The significant changes registered everywhere of the
      condition of health of the adult and children population in the centres of
      ecological risk and trouble call more and more urgently for considering the
      condition of health an economic category, and the quality of health of the
      population a limiting factor of the strategy of social-economic development of
      the territories of Siberia.

PMID- 15736630
TI  - Community based physiotherapy services in the Kivalliq Region of Nunavut, Canada.
AB  - OBJECTIVES: Community based physiotherapy services are an integral component of
      the recent implementation of a medical rehabilitation program in the Kivalliq
      Region of Nunavut. Since the year 2000, the Inuit people of Canada's central
      Arctic have had direct access to physiotherapy in their home communities. STUDY
      DESIGN: A quantitative review of physiotherapy services from January 1, 2001 to
      December 31, 2002. METHODS: Workload measurement data gathered by the
      physiotherapists in the field will be utilized to present information on referral
      sources, location of services provided, client diagnoses and average duration of
      treatment provided. Administrative data will provide information on staffing
      complements and challenges to date. The need for physiotherapy referrals out of
      the Kivalliq Region will be reviewed. RESULTS: Referral sources to physiotherapy
      services are varied, the majority of diagnoses are musculoskeletal in nature,
      followed by neurological and cardiovascular. Recruitment of the physiotherapy
      positions has been successful to date. Referrals out of the region for
      physiotherapy services have been rare since community based services have begun.
      CONCLUSIONS: Access to physiotherapy services by the residents of the Kivalliq
      Region has been significantly enhanced since the implementation of the medical
      rehabilitation program.

PMID- 15736631
TI  - Development of a community-based medical rehabilitation programme in the Kivalliq
      Region of Nunavut, Canada.
AB  - OBJECTIVE: In 2000, the University of Manitoba and the Department of Health and
      Social Services of Nunavut, Canada, jointly embarked upon the development of a
      community-based medical rehabilitation programme in the Kivalliq Region of
      Canada's central Arctic. Two main objectives were identified in moving forward
      with the implementation of a rehabilitation programme. Firstly, to conduct a
      region wide community needs assessment for rehabilitation services for all age
      groups of all residents of the Kivalliq Region of Nunavut. Secondly, to provide
      information from which a community-based rehabilitation therapy programme could
      be developed. METHODS: A community needs assessment of the Kivalliq Region was
      carried out to guide the implementation of physiotherapy, occupational therapy
      and speech language pathology services. RESULTS: There are now two
      physiotherapists, one occupational therapist, and one speech language pathologist
      providing rehabilitation services to the residents of the Kivalliq Region of
      Nunavut. The results of this needs assessment, the challenges and successes of
      this medical rehabilitation programme are discussed. CONCLUSION: The total
      population of the service area is approximately 8,000 people, the significant
      majority of whom self-report as Inuit, and are widely dispersed over eight
      communities. Despite the challenges in terms of culture, geography and
      recruitment of introducing a rehabilitation program in Canada's north, the
      residents of the Kivalliq Region now have a viable model of receiving
      rehabilitative intervention in their home communities.

PMID- 15736632
TI  - Conceptions and dimensions of health and well-being for Metis women in Manitoba.
AB  - Because of the continuing poor health status of Aboriginal populations in Canada,
      along with increasing opportunity for Aboriginal designed health surveys, it is
      argued that policies and programs, and the research from which they are derived,
      should be more solidly grounded within Aboriginal understandings of health and
      well-being. Survey research for Aboriginal populations usually draws on questions
      developed by and for mainstream Canadians. This paper stems from the author's
      master's thesis study that elicited adult and elder Metis women's description of
      'what constitutes health' and 'what constitutes well-being'. Outlined are
      descriptions of Metis women's Conceptions of Health and Conceptions of Well
      being, as well as Dimensions of Well-Being that should be included in health
      survey research.

PMID- 15736633
TI  - Reduction of amputation rates among Alaska Natives with diabetes following the
      development of a high-risk foot program.
AB  - OBJECTIVE: The prevalence of diabetes is increasing rapidly among Alaska's
      Indian, Eskimo and Aleut populations. Approximately half the Native people with
      diabetes have no road access to hospitals or physicians, presenting a challenge
      in the attempt to prevent lower extremity amputation as a complication. In late
      1998 funding became available for diabetes prevention and treatment among Native
      Americans. The tribal health corporations in Alaska decided to use a portion of
      this funding to implement a high-risk foot program to decrease the amputation
      rate. PROGRAM DESIGN: The program initially involved a surgical podiatrist who
      provided training to local staff and performed preventive and reconstructive
      surgery on several patients with impending amputations. The program then provided
      training for a physical therapist to become a certified pedorthist. This
      individual established the long-term maintenance phase of the program by
      conducting diabetic foot clinics routinely at the Alaska Native Medical Center, a
      referral center in Anchorage. He also travels to other regions of the state to
      provide training for village and hospital-based health care providers and to
      conduct field clinics. A system was established in a common database management
      program to track the patients' foot conditions. Patient education is emphasized.
      RESULTS: The overall amputation incidence among all Alaska Native patients with
      diabetes decreased from 7.6/1,000 in the pre-program period (1996 to 1998) to
      2.7/1,000 in the post-program period (1999-2001) (p<.001). The rate among Aleuts,
      who previously had the highest amputation incidence, decreased from 17.4/1,000 to
      3.1/1,000 over the same time periods (p<.001). Among people who had had diabetes
      at least 10 years, the overall amputation incidence decreased from 16.4/1,000 to
      6.8/1,000 (p=.021); among Aleuts the rate fell from 24.5/1,000 to 2.6/1,000
      (p=.01). CONCLUSIONS: Though longer follow-up is needed, these data suggest that
      even in populations living in isolated regions, diabetic amputations can be
      prevented by a coordinated system to identify high-risk feet and provide
      preventive treatment and education in the context of a comprehensive diabetes
      management program in an integrated health system.

PMID- 15736634
TI  - Speech language pathology services in Kivalliq Region of Nunavut, Canada.
AB  - OBJECTIVES: To provide a review of Speech Language Pathology services in the
      Kivalliq Region of Nunavut, Canada, since its inception. Referral sources,
      reasons for referral and discharge will also be shown for seven of the
      communities in the Kivalliq Region. STUDY DESIGN: A quantitative and qualitative
      survey of the services received for the 26-month time period from January 2001 to
      February 28th, 2003. METHODS: A record review of Speech Language Pathology
      services was conducted. Referral sources in each community, the rate of
      referrals, reasons for discharge and changes in abilities of three clients were
      examined. RESULTS: The rate of referrals increased as the service became more
      familiar. Small increases in client abilities were noted over the specified time
      period. CONCLUSION: Speech Language Pathology services are being utilized more
      effectively as the referral sources become more familiar with the program.

PMID- 15736635
TI  - Evaluation of a mobile diabetes care telemedicine clinic serving Aboriginal
      communities in Northern British Columbia, Canada.
AB  - INTRODUCTION: In British Columbia, Aboriginal diabetes prevalence,
      hospitalization and mortality rates are all more than twice as high as in the
      rest of the population. We describe and evaluate a program to improve access to
      diabetes care for Aboriginal people in northern communities. STUDY DESIGN: Cost
      effectiveness evaluation. METHODS: A diabetes nurse educator and an ophthalmic
      technician travel to Aboriginal reserves, offering people with diabetes services
      recommended in current clinical practice guidelines: retinopathy screening by
      digital retinal fundus photography, glaucoma screening by tonometry, point-of
      care urine and blood testing to detect microalbuminuria and dyslipidemia and to
      measure glycated hemoglobin, foot examinations and foot care advice, blood
      pressure and height and weight measurement and diabetes care advice. Via
      electronic communication, an ophthalmologist and an endocrinologist in Vancouver
      review the findings and supervise the mobile clinic staff. RESULTS: During the
      first year, 25 clinics were held at 22 sites, examining 339 clients with
      diabetes. Exit surveys showed high levels of client satisfaction. Mean cost per
      client (Cdn dollars 1,231) was less than for the alternative, transporting
      clients to care in the nearest cities (Cdn dollars 1,437). CONCLUSIONS: The
      mobile clinic is cost-effective and improves access to the recommended standard
      of diabetes care.

PMID- 15736636
TI  - How clients choices influence cancer care in northern Aboriginal communities.
AB  - OBJECTIVES: To illustrate how personal choice, or client self-reliance, is a
      determining factor in the management of cancer patients' care in northern
      Aboriginal communities. STUDY DESIGN: Multiple-site study done in the
      northwestern part of the Canadian Province of Ontario. METHOD: In-depth
      interviews with professionals and paraprofessionals involved in community-based
      delivery of cancer care. RESULTS: Study details how perceived care options,
      gender, awareness of disease and treatment, reaction to system-linked problems in
      care delivery, as well as cultural preferences influence clients' choices and
      care outcomes. CONCLUSION: The study underlines the interdependence between
      personal choice and the health care system; "bad" experiences with the system
      cause clients to disengage from care, while client disengagement results in
      reduced care options.

PMID- 15736637
TI  - E-mail contact between patients and doctors in primary health care.
AB  - OBJECTIVES: With the purpose of facilitating contact between patients and the
      doctors at the clinic a system for e-mail contact was developed. A system for
      evaluation is integrated in the software. METHOD: Dialogue between the authors
      and Dansk Telemedicin A/S, a firm specialized in web-based telemedicine. RESULTS:
      A system called E-laegen, which means E-doctor, consisting of a number of
      sequential web pages accessed through the Internet.

PMID- 15736638
TI  - Helping Inuit clients: cultural relevance and effective counselling.
AB  - OBJECTIVES: The objective of this study was to investigate the fit between Inuit
      conceptions of effective helping and Western counselling. STUDY DESIGN/METHODS:
      The essential components and value foundations of effective Western counselling,
      including multicultural counselling, were identified from primary and secondary
      counselling texts. Inuit traditional values and helping practices were identified
      from the transcripts of interviews with Inuit elders. Interviews with 5 younger
      Inuit provided information about the counselling needs of contemporary Inuit.
      Grounded theory analysis of all texts and interview transcripts was used to
      determine each informant group's conceptions of the elements of effective
      counselling. A comparative chart was then constructed of the important
      relationship factors, strategies and process, and effective interventions
      identified by each informant group. RESULTS: The values and relationship factors
      of effective counselling are similar in traditional and Western helping, and
      these same factors are important to the contemporary Inuit interviewed.
      Affective, behavioural and cognitive interventions were used traditionally;
      modern generic counselling also uses a variety of strategies from these three
      primary categories. Cognitive and cognitive-behavioural approaches to problem
      solving were traditionally of primary importance, with expression of feelings
      also seen as essential. CONCLUSION: Western and traditional Inuit helping
      correspond, and cognitive/cognitive-behavioural approaches especially complement
      Inuit cultural practice.

PMID- 15736639
TI  - Knowledge translation and indigenous knowledge.
AB  - OBJECTIVE: We wanted to evaluate the interface between knowledge translation
      theory and Indigenous knowledge. DESIGN: Literature review supplemented by expert
      opinion was carried out. METHOD: Thematic analysis to identify gaps and
      convergences between the two domains was done. RESULTS: The theoretical and
      epistemological frameworks underlying Western scientific and Indigenous knowledge
      systems were shown to have fundamental differences. CONCLUSION: Knowledge
      translation methods for health sciences research need to be specifically
      developed and evaluated within the context of Aboriginal communities.

PMID- 15736640
TI  - An ethics committee for medical research in Greenland: history and challenges.
AB  - Ethical appraisal of medical protocols for research is now well accepted, and
      needed when research may carry side effects and risks that may be difficult to
      understand for the people invited to take part in research. We argue that time
      has come for Greenland to establish a formal medical research ethics committee
      with a legal basis. With proper use of modern means of communication it should be
      possible to run a committee at a reasonable cost. We believe that such a
      committee should closely follow international standards. One urgent matter to get
      under a formal set of rules is to set proper standards for storage of biological
      samples taken from people in Greenland.

PMID- 15736641
TI  - The Danish Youth Survey 2002: asking young people about sensitive issues.
AB  - OBJECTIVES: To explore ethical, legal and practical issues related to conducting
      a youth survey in Denmark on sexual experiences before the age of 15 and thereby
      achieve reliable data on child sexual abuse. STUDY DESIGN AND METHODS: The
      relevant authorities were consulted on possible legal and ethical objections. By
      a pilot study based on conventional self-administered questionnaires, information
      was obtained about the reactions of school boards, teachers and 9th grade
      students. RESULTS: The necessary conditions were present for the implementation
      of a nationwide anonymous youth survey without obtaining parental consent. The
      Central Scientific Ethical Committee had no objections. In a number of fields,
      Danish legislation accords 15-to-18-year-olds the competence to make independent
      decisions regarding their personal circumstances, and the UN Convention of
      Children's Rights states that a child's viewpoints must be accorded appropriate
      significance in relation to that child's age and maturity. In the pilot study, no
      negative reactions were observed among the students and school authorities. About
      25% of the students had difficulties in filling the questionnaire. No student
      made use of the accompanying offer of counselling. CONCLUSION: An anonymous youth
      survey based on computer-assisted self-interview (CASI) would increase the
      validity of youth surveys on child sexual abuse to which no ethical or legal
      objections were found.

PMID- 15736642
TI  - Health research in Greenland: start with the children.

PMID- 15736643
TI  - The Greenlandic research database: a population-based research resource.
AB  - Information on past exposures is often warranted in health studies in Greenland,
      as living conditions have changed markedly in this century. To provide a
      longitudinal population-based research tool with such information the Department
      of Epidemiology Research at Statens Serum Institut has established 'The
      Greenlandic Research Database', a comprehensive population-based database
      comprising data from Greenland from national registers, population-based
      longitudinal and cross-sectional studies and human biological samples from 1979
      to the present day.

PMID- 15736644
TI  - Morbidity and health survey of wintering members in Japanese Antarctic research
      expedition.
AB  - STUDY DESIGN: The Japanese Antarctic Research Expedition (JARE) started in 1956.
      Syowa Station is the mother station of JARE at 69 degrees 00'S and 39 degrees
      35'E in East Antarctica. An epidemiological survey of the wintering team of JARE
      was carried out based on the annual reports of JARE over the period 1956-2001.
      METHODS: The total number of personnel was 1,236 including 3 females. The age of
      personnel was from 21 to 56 (average 33.1). We examined the proportion of
      personnel who had contracted disease with healthy personnel, as reported by the
      medical department at Syowa as well as a health survey of the latest party by
      biochemical analyses. RESULTS: The total number of diseases was 4,760. The ratios
      of surgical-orthopedic, internal medical, and dental cases were 45%, 23%, and
      13%, respectively. Only one death from a blizzard was recorded. In the latest
      party, serum levels for triglyceride, calcium, and gamma-glutamyl transpeptidase
      increased during the wintering period. CONCLUSION: The very low mortality of JARE
      may be due to the effective personnel selection and that there have been no
      severe accidents. There has been no deterioration in nutritional parameters in
      JARE recently.

PMID- 15736645
TI  - Consumption guideline for cadmium in moose meat in northern British Columbia,
      Canada.
AB  - INTRODUCTION: Disturbed by reports of high concentrations of cadmium in large
      land mammals in Arctic Canada, community members wondered if they should eat less
      moose (Alces alces). STUDY DESIGN: Risk assessment modelling. METHODS: We
      measured cadmium concentrations in moose tissues donated by food hunters. As a
      conservative assumption, we took the upper limits of the 95% confidence intervals
      for the means. Cadmium intake from other sources we estimated using risk
      assessment models. Assuming a Tolerable Daily Intake of cadmium of 1 microgram
      per kg body weight per day, we calculated maximum allowable intakes of moose
      kidney, liver and muscle. RESULTS: For a non-smoking 70 kg adult, allowable
      monthly intakes are: 52 kg of moose muscle, or 137 g of kidney, or 516 g of
      liver. Allowable intakes varied by age and in proportion to body weight.
      Cigarette smokers (one to 1.5 packs per day) reach the limit even if they consume
      no moose at all. CONCLUSIONS: Adults may continue to eat moose kidney and liver
      occasionally and in moderate amounts, but children and cigarette smokers should
      not eat these organs at all. Consumption of moose muscle need not be restricted.
      Monitoring of cadmium concentrations in moose should continue.

PMID- 15736646
TI  - Semen quality in Greenland.
AB  - OBJECTIVES: To quantify semen quality in the Greenlandic population. STUDY
      DESIGN: A cross-sectional study including recently proven fertile men from four
      regions including nine municipalities and one settlement in Greenland. METHODS:
      The samples were analysed for sperm cell concentrations and motility using
      standard methods. RESULTS: In total 201 semen samples were collected. The median
      sperm cell concentration of fertile men in Greenland was 53 x 10(6) sperm
      cells/ml, with a median sperm cell volume of 3.2 ml, a total sperm count of 185.6
      x 10(6) sperm cells and a median motility of 60%. Regionally there were no
      statistical significant difference in sperm counts, but the sperm cell motility
      differed among regions, with the lowest sperm cell motility found in semen
      samples collected on the east coast. Overall sperm cell concentration and total
      sperm count in Greenland seems to be in the lower range compared to studies from
      Europe, USA and Japan. CONCLUSION: Within Greenland the sperm cell concentration
      appears to be similar in different regions, but sperm cell motility tends to be
      lower in men from the east coast. This may be related to the higher
      organochlorine exposure level previously demonstrated in this population.

PMID- 15736647
TI  - Blood concentrations of persistent toxic substances in the indigenous communities
      of the Russian Arctic.
AB  - OBJECTIVES: Investigation was carried out within the framework of the large-scale
      international project "Persistent Toxic Substances (PTS), Food Security and
      Indigenous People of the Russian North" under RAIPON/AMAP/GEF aegis. Objectives
      of the project are to obtain comprehensive information on exposure of indigenous
      populations to contaminants through food chains (and other sources), and to
      investigate the possible health effects connected to this exposure. Four regions
      of Russia are involved in the project: Kola Peninsula (Murmansk oblast), Nenetsk
      okrug (Pechora river basin), Taimyr Peninsula, Chukotka Peninsula. METHODS:
      Questionnaire and paired sampling of maternal/cord blood among indigenous women
      at childbirth (more than 250 persons) as well as among general indigenous
      population (more than 1,400 persons), additionally breast milk sampling of
      lactating women (more than 50 persons) in Chukotka was conducted. About 700 blood
      samples have been analyzed at the Center for Environmental Chemistry, SPA
      "Typhoon" (Obninsk, Russia), the Regional Center "Monitoring of the Arctic", RCMA
      (St. Petersburg, Russia), the Norwegian Institute for Air Research, NILU (Tromso,
      Norway) and at INSPQ (Sainte-Foy, Quebec, Canada). RESULTS AND CONCLUSIONS: On
      the whole, PTS in human blood of the Russian Arctic natives are similar to those
      in the coastal areas of Greenland and Canada, and for some POPs such as
      toxaphenes and mirex, these levels are lower.

PMID- 15736648
TI  - The mystery of primary biliary cirrhosis in British Columbia's First Nations
      people.
AB  - OBJECTIVES: Primary biliary cirrhosis (PBC) is a rare chronic, progressive liver
      disorder leading to transplantation or death, with a known autoimmune basis.
      Although it has been estimated to have a prevalence of between 2-5 cases per
      100,000 worldwide, it is not rare in British Columbia's (BC) First Nations (FN)
      peoples, where it is the leading indication for liver transplant in that
      population. A study of indications for liver transplant from 1989 to 1998
      demonstrated that although just 3.9% of the population of BC is of FN descent,
      25% of those requiring transplantation for PBC were of FN descent. From this, it
      can be calculated that PBC is about 8 times more common than in the non-native
      population. METHODS: We studied the prevalence of PCB on Vancouver Island, where
      about 50% of the cases on the transplant Society List are reported. RESULTS AND
      DISCUSSION: As with many autoimmune diseases, PBC affects women predominantly.
      Genetic predisposition and environmental factors are thought to contribute to the
      development of PBC. A strong genetic component is postulated in the BC population
      where 6 affected individuals are all related through common great grandparents.
      Nonetheless, both genetic and environmental components are being explored in this
      unique population.

PMID- 15736649
TI  - Cholestasis Familiaris Groenlandica/Byler-like disease in Greenland--a population
      study.
AB  - OBJECTIVES: Cholestasis Familiaris Groenlandica (CFG, or progressive familiar
      intrahepatic cholestasis type 1 (PFIC1)) is a very common lethal recessive
      inherited disease in Greenland. A missense mutation, 1660G>A (asp554asn) in the
      gene ATP8B1 causes the disease (Klomp et al. 2000). STUDY DESIGN: A family study
      examining medical files from the period 1951-2003 from East Greenland resulted in
      46 cases of PFIC1 and more than 220 relatives showing carrier status. Further,
      random blood sample testing 953 anonymous persons from 11 major cities or
      districts all over Greenland have been analysed for carrier status of the
      mutation. METHODS: A sensitive PCR method is developed to distinguish between
      normal and mutant alleles for ATP8B1 in the Greenland population. RESULTS: The
      mutation 1660G>A is found in all areas of Greenland, and the frequency of the
      mutant allele vary all over the country. A shockingly high frequency for the
      mutant allele is found in East Greenland in Ittoqqortoormiit (0.16) and in
      Tasiilaq (0.077), whereas in Northwest Greenland lower frequencies are found in
      Uummannaq and Ilulissat (0.032), and Maniitsoq (0.005). CONCLUSIONS: The high
      frequency of the mutation in East and Northwest Greenland strongly indicates that
      routine screening of the population for carrier status should be done.

PMID- 15736651
TI  - Cancer in Greenlandic Inuit 1973-1997.
AB  - OBJECTIVES: During the second half of the 20th century living conditions of the
      Inuit populations in the Arctic have undergone major transitions. The objective
      was to investigate how the cancer pattern was affected by these changes, using
      data from the Danish Cancer Registry and the Civil Registration System. RESULTS:
      In the period 1973-1997 total cancer incidence increased by 4% per 5 years for
      men and 6% per 5 years for women. The incidence of lung, stomach, breast and
      colon cancer increased in both sexes, whereas the incidence of cervical cancer
      decreased. CONCLUSIONS: Thus, the overall cancer incidence among Greenlandic
      Inuit is increasing as a result of increases in several cancers that are common
      in Western populations. In contrast to global trends, a significant increase in
      the incidence of stomach cancer in both sexes was observed.

PMID- 15736650
TI  - Cholestasis Familiaris Groenlandica: an epidemiological, clinical and genetic
      study.
AB  - OBJECTIVES: Accumulation of Cholestasis Familiaris Groenlandica (CFG) or
      progressive familial intrahepatic cholestasis type 1 (PFIC1) occurs in indigenous
      Inuit families in Greenland. It is an autosomal recessive inherited liver
      disease. From early childhood the children suffer from failure to thrive,
      jaundice, pruritus and enlarged liver. Affected persons generally die very young.
      STUDY DESIGN: Patients' information has been collected from the Greenlandic death
      register and hospital records. METHODS: Detailed genealogy including clinical
      description and examination if possible. Interviews of parents and relatives,
      linkage and DNA analysis of the probands and the closest relatives have been
      studied. RESULTS: 46 affected cases from a highly inbred population have been
      diagnosed since 1943. The disease is caused by a missense mutation in the FIC1
      gene ATP8B1, chromosome 18q21. Six affected children are alive aged 1-21 years.
      Among the tested relatives 220 are heterozygote. One prenatal diagnosis has been
      performed. CONCLUSION: The mutation causing Cholestasis Familiaris Groenlandica
      is widespread in Greenland, but accumulation is seen in certain areas. The
      disease is burdensome for the child, the parents and the Greenlandic society.
      Genetic counselling and carrier screening are strongly recommended.

PMID- 15736652
TI  - Human papillomavirus and cervical dysplasia in Nunavut: prelude to a screening
      strategy.
AB  - OBJECTIVES: To determine the prevalence of oncogenic human papillomavirus' (HPV)
      in Nunavut and to assess the association between HPV and squamous intraepithelial
      lesions (SIL) as a prelude to planning a better screening strategy. STUDY DESIGN:
      A cross-sectional study was conducted on the Pap-screened populations in 19
      communities in Nunavut, Canada. SIL was determined using Liquid-based cytology,
      and HPV testing was done using the Hybrid Capture II assay. RESULTS: Prevalence
      of oncogenic HPVs in 1,290 women ages 13-79 was 26% and of Cervical Dysplasia was
      7.2%. Over 90% of women with SIL had positive HPV tests. Over 75% of women who
      were HPV positive but SIL negative were under 30 years of age. CONCLUSION:
      Consideration should be given to using liquid-based cytology for Pap testing.
      Also consider concurrent HPV testing in those over 30 years old and reflex
      testing of HPV in those under 30 years old with a positive HPV test.

PMID- 15736653
TI  - Incidence of viral hepatitis B and vaccination in the Arkhangelsk region, Russian
      Federation.
AB  - INTRODUCTION: Hepatitis B (HB) incidence in Russia decreased from 36.6 in 1997 to
      19.8 per 100,000 population in 2002. Despite this fact, there is an increasing
      transmission rate among young adults. STUDY DESIGN: Survey of official
      epidemiological surveillance data from 1997 to 2002 and results of serological
      screening of the population in the Arkhangelsk region are represented. METHODS:
      Incidence of HB was compared and age-specific analysis was performed during the
      survey period. Immunofluorescent method was used to determine HB carriage status.
      RESULTS: From 1997 to 2002, incidence of HB increased from 11.3 to 12.1 per
      100,000. Young adults between 15 and 29 years old were the most affected group in
      2001 (more than 60% of all cases). The leading route of transmission in this
      group was intravenous one. Vaccination of newborns resulted in decrease of HB
      incidence among children under 14 years from 8.7 in 1997 to 4.5 per 100,000 in
      2002. Serum of 13,128 future mothers was investigated in 2001, 208 women (1.58%)
      appeared to be positive (there were only 1.22% carriers in this group in 1999).
      CONCLUSIONS: Analysed data show the importance of immunisation against Hepatitis
      B not only among newborns, but also among teenagers. In addition, special
      attention should be paid to the growing problem of Hepatitis B carriage among
      pregnant women.

PMID- 15736654
TI  - Respiratory tract infections in Greenland: results of an audit project.
AB  - OBJECTIVES: To elucidate and improve quality of diagnosis and treatment of
      respiratory tract infections in Greenland. STUDY DESIGN: All district medical
      officers and nursing staff in the Greenlandic coastal health services were
      invited to participate in the study. Twenty-five district medical officers and
      the nursing staff from nine districts completed the project and registered in a 3
      week period 1,163 contacts involving respiratory tract infections. METHODS: Self
      registration according to the Audit Project Odense (APO) method on a simple APO
      registration chart. All contacts involving respiratory tract infections were
      registered with regard to sex, type of contact, contact form, infection focus,
      diagnosis and treatment, origin of infection, antibiotic treatment, choice of
      antibiotics and possible sick-leave. RESULTS: Of the 1,163 registered contacts
      lung infections represented 26%, throat infections 22% and otitis media 16%.
      Paraclinical tests were performed in 32% of the cases, 47% of the cases were
      treated with antibiotics, in 2/3 of the cases with penicillin V. The use of
      paraclinical tests was somewhat lower and the use of antibiotics was higher than
      in Denmark. CONCLUSION: The study showed that it is possible to carry out an APO
      audit in Greenland, and that there was a moderate difference in the diagnosis and
      treatment between Greenland and Denmark. An increased use of paraclinical tests
      may result in quality improvement.

PMID- 15736655
TI  - Helicobacter pylori infection in Greenlandic patients with dyspepsia.
AB  - OBJECTIVES: The aim was to evaluate the incidence of Helicobacter pylori (HP)
      infection in Greenland, to assess the value of the test "Helicobacter antigen in
      faeces" as a diagnostic tool and to determine the level of antibiotic resistance.
      STUDY DESIGN: 100 consecutive patients with dyspepsia who visited for endoscopic
      gastric examination were included. The patients had to be born in Greenland and
      to be > or = 18 years old. METHODS: Samples for HP antibody in blood, HP antigen
      in faeces, urease test on biopsies were collected from the patients. Gastric
      biopsies were cultured for HP bacteria, and antibiotic resistance was tested.
      Patients with positive urease test and/or antigen in faeces and/or positive
      culture were treated simultaneously with Amoxicillin, Metronidazole and
      Esomeprazole for 1 week. Patients with duodenal or gastric ulcer were
      endoscopically re-examined 8 weeks later. Patients with proven HP infection but
      without ulcer submitted a faeces sample 8 weeks after the eradication. RESULTS:
      77 patients were considered HP infected, and received treatment. Only 32% of them
      were eradicated sufficiently. CONCLUSION: HP antigen in faeces test is useful as
      a diagnostic tool and for control of therapy. A change in strategy of HP
      treatment in Greenland is a must, presumably preceded by an elucidation of
      microbial sensitivity.

PMID- 15736656
TI  - Tuberculosis in Greenland--still a problem to bear in mind: development and
      strategy.
AB  - OBJECTIVES: Tuberculosis is still a disease to be taken seriously in Greenland.
      After a ten-year period in oblivion, the incidence of tuberculosis has been shown
      to be rising during the nineties. A central tuberculosis-group was constituted in
      1997 in order to monitor and control the situation. A centrally placed TB nurse
      was established to support and supervise local health authorities. STUDY DESIGN:
      Retrospective review of registered incidents of tuberculosis from all health
      districts from 1997 until 2002. Review of reports from the TB nurse. METHODS:
      Quality assessment of treatment and subsequent control was systematically
      conducted by the TB nurse. RESULTS: Microepidemics were observed in various
      health districts. The TB nurse was a positive assistance in case finding,
      tracking sources of infection, identifying disease carriers, guidance and
      instruction of local health care workers. Knowledge of TB and continuity amongst
      health care workers along with a fragile manning situation are shown to be
      important determining factors in the effort to control TB. With a former high
      prevalence of TB hidden pools may still be likely to turn up. CONCLUSION: Health
      care workers still need to focus on tuberculosis in order to diagnose individual
      incidents, to secure proper treatment according to guidelines, to track sources
      of infection, to identify disease carriers, and to prevent further spreading into
      the community. The interventions of the TB nurse are an efficient tool to control
      microepidemics at a local level in seeing that proper registration, treatment and
      specific prophylactic interventions are being carried out.

PMID- 15736657
TI  - Tuberculosis in Greenland--current situation and future challenges.
AB  - OBJECTIVE: To describe the tuberculosis (TB) epidemiology in Greenland in 1998
      2002 and to identify possible obstacles for reducing the TB incidence. STUDY
      DESIGN/METHODS: TB notification data were collected from the annual reports of
      the Chief Medical Officer, and culture verification data were collected from the
      International Reference Laboratory of Mycobacteriology at Statens Serum Institut,
      Denmark. RESULTS: The TB incidence in Greenland reached a peak of 185/100,000 in
      2001. In 1999-2001, the majority of cases were related to an outbreak in the
      Southern districts. In 1998-2002, 0.5% drug-resistance was found among patients
      living in Greenland in contrast to 13.1% drug-resistance found previously among
      Inuit patients in Denmark. In 1998-2001, microscopy positive cases made up 65% of
      all culture confirmed cases and DNA subtyping demonstrated the emergence of
      Mycobacterium tuberculosis strains that were previously infrequently found.
      CONCLUSION: It is important to eliminate factors that fuel the epidemic and to
      improve general living conditions in Greenland. Treatment seems effective as
      limited drug-resistance is detected. TB reduction will therefore depend on early
      detection of active disease and thorough contact tracing. Greenland will face a
      pool of persons latently infected some of whom will progress to active disease.
      Sufficient resources need to be allocated for TB control in the years to come.

PMID- 15736658
TI  - A fresh look at an old vaccine: does BCG have a role in 21st century Canada?
AB  - INTRODUCTION: In Canada, bacille Calmette-Guerin (BCG) vaccine is now primarily
      given to First Nations and Inuit (FNI) neonates living in tuberculosis (TB)
      endemic areas. With declining TB rates, attention has shifted from the protective
      effects of BCG to reports of serious vaccine-associated adverse events (VAAE).
      METHODS: Surveillance data were reviewed to assess TB burden and trends, BCG
      coverage, and VAAE among FNI people in the 1990s. RESULTS: TB among FNI people
      living on reserve was 25 times higher than the Canadian-born, non-Aboriginal rate
      between 1997 and 2000. Paediatric TB rates declined from 149 per 100,000 in 1990
      to 23 per 100,000 in 2000, with one case of TB meningitis and one TB fatality
      (due to congenital TB) reported in the 0-4 age group. Nine cases of disseminated
      BCG infection occurred in a 21-year period among children with congenital or
      acquired immunodeficiencies. The estimated rate of disseminated BCG infection was
      205 per 1,000,000 (95% CI 62-678). DISCUSSION: BCG provides protection against
      severe forms of childhood TB. However, in a country with publicly funded health
      care and declining TB rates, it is important to consider VAAE. Disseminated BCG
      infection increases mortality among children with immunodeficiency disorders,
      which now have successful therapies. Although TB remains a threat in FNI
      communities, early detection and treatment of TB infection may be a more
      appropriate intervention.

PMID- 15736659
TI  - The outcome of perinatal care in Inukjuak, Nunavik, Canada 1998-2002.
AB  - INTRODUCTION: From the 1950s women in Nunavik were transferred to South Quebec to
      give birth. Since 1986 women have had the opportunity to give birth in
      Povungnituk, Nunavik, and the education of community midwives began. Inukjuak, a
      small community in Nunavik, was included in the project in 1998. There is no
      possibility for caesarean section or transfer during birth, in any of the places.
      Women can be transferred in pregnancy or post partum to the small hospital in
      Povungnituk or to a specialist obstetrical unit in Montreal. STUDY DESIGN: A 5
      year retrospective survey of the perinatal care in Inukjuak. METHOD: Data were
      collected from 1. Birth registrations. 2. Antenatal records in Inukjuak. 3.
      Records and follow-up of medical evacuations to either Povungnituk or Montreal.
      RESULTS: Of the 182 women from Inukjuak who gave birth, 72.5% of the women gave
      birth in their own community. 4.5% women or/and newborn was evacuated for reasons
      related to birth. The rate of premature birth is 3.3% of all pregnant women from
      Inukjuak. The PMR is 0.5% of all babies born by women from Inukjuak and 0.7% of
      all babies born in Inukjuak. CONCLUSION: Three out of four women can stay in
      Inukjuak and give birth with a PMR of 0.7%

PMID- 15736661
TI  - The importance of family to health, development and welfare of children.
AB  - OBJECTIVES: Recent investigations have shown that a number of families in
      Greenland have problems related to parents' use of alcohol. One of the
      consequences is that children get more difficult conditions during childhood.
      Children suffer when their parents have alcohol-related problems. An alcoholic
      parent is generally not able to meet the needs of his or her child. Many children
      are very lonely and do not discuss their thoughts, their situation or their
      problems with anyone. Some children get serious psychosocial problems as grown
      ups. RESULTS AND CONCLUSIONS: Professionals who work with children in health
      services, social services or within the school system are generally not
      adequately aware of the importance of family to the children's reactions. This
      means that the children are at risk of being treated only for symptoms when the
      unity of child and family is not adequately taken into account. Prevention has to
      focus on the first steps. Children must be allowed to talk about their problems.
      The whole family should be included in the treatment.

PMID- 15736660
TI  - Preterm delivery among Inuit women in the Baffin Region of the Canadian Arctic.
AB  - OBJECTIVE: To evaluate the rate and causes of preterm (before 37 weeks gestation)
      and very preterm (before 32 weeks gestation) delivery among a population of Inuit
      living in Canada. STUDY DESIGN: Three-year retrospective cross-sectional review
      of charts for patients delivering in the Baffin Region of Canada. RESULTS: There
      were 938 births over the study period; 95% to Inuit women. Inuit women had a
      preterm delivery rate of 18.2% and a very preterm delivery rate of 2.4%, more
      than twice the Canadian national average. Sociodemographic risk factors for
      preterm delivery including substance use, young age, single marital status, and
      poor nutrition, occurred more frequently among Inuit women compared to non-Inuit
      women, but were not independently associated with prematurity. Known medical and
      obstetrical risk factors were associated with preterm delivery among Inuit women;
      history of prior preterm delivery, multiple pregnancy, placenta previa, poor
      weight gain and vaginal bleeding after 20 weeks gestation. Hospitalization rates
      and infant mortality were higher among preterm infants. The most common
      indication for hospitalization was respiratory infection (51.1%) followed by
      other infection (15.8%). CONCLUSION: Inuit women had preterm and very preterm
      delivery rates more than twice the Canadian national average. Preterm delivery
      was associated with several medical risk factors and resulted in significant
      increases in infant hospitalization and mortality.

PMID- 15736662
TI  - Childcare immunization programme--to what extent are children covered by
      vaccinations in Greenland?
AB  - OBJECTIVES: New vaccines in the child healthcare programme are regularly
      considered. When considering the introduction of the Hepatitis-B vaccine into the
      programme, it was asked to what extent children in Greenland were actually
      covered by the existing immunization series. Would introducing new vaccines make
      any sense if the percentage of children immunized was shown to be low? A
      telephone enquiry conducted in 2000 showed a tendency of very high percentage of
      full coverage per child (98-99%) in small cities and settlements, as health
      visitors had a policy of checking up on the immunization status for each child.
      In big cities and Nuuk, parents alone have the responsibility of having their
      child immunized. The coverage was a guess of 85-95% for infants, falling as the
      child grows older. STUDY DESIGN: Retrospective review of registration from all
      Greenlandic health districts. METHODS: The registration included the number of
      immunized children in each group of age according to the childcare immunization
      programme. The collected data were compared to the number of children per age
      group in each health district. RESULTS AND CONCLUSION: The conclusion must be
      taken with some reservation on the basis of several aspects of uncertainty. As a
      whole, the tendencies show reasonably high vaccination coverage countrywide, but
      variations between districts are great. A number of children probably have their
      vaccination postponed somewhat in relation to recommended age, but it is fairly
      evident that the majority of these children are dealt with later. The coverage in
      a few districts is lower than desired, especially concerning DiTe4 and MMR2.

PMID- 15736663
TI  - Infection control in day-care centres in Greenland.
AB  - OBJECTIVES: The aim of this study was to determine hygienic habits and
      precautions taken with main focus on hand hygiene, cleaning and laundry in day
      care centres in Greenland. METHODS: In the period 2000-2002 we investigated 33
      day-care centres in towns along the west coast of Greenland using a
      questionnaire. The majority of the day-care centres (18/33) were found in the
      biggest towns in Greenland Nuuk and Sisimiut. RESULTS: The institutions covered
      34% of children attending day-care centres in Greenland. Although most caregivers
      and children would wash their hands before meals and after changing
      diaper/toilet, not all did so. One third of caretakers did not wash hands after
      wiping a child's nose. Paper towels were only available as recommended in 25% of
      day-care centres. Linen was washed weekly or more often per month, but at lower
      temperatures than recommended. Most floors were washed daily. CONCLUSIONS: The
      day-care centres in general did not follow hygienic recommendations sufficiently,
      and the hygienic behaviours resembled more those of home. For public institutions
      this is not sufficient to prevent cross-contamination, as the risk of spread of
      microorganisms is high in institutions with many contacts. Caregivers are the
      most important role models in teaching the child good hygienic habits such as
      hand hygiene. Hygienic education of caregivers and early hygienic training of
      children, preferably already in nursery, is therefore important and should be
      strengthened.

PMID- 15736665
TI  - Reducing unwanted pregnancies in Greenland.
AB  - OBJECTIVES: In 2002 the number of births in Greenland was 940 and the number of
      abortions 821. The Home Rule Government in Greenland and PAARISA, The Department
      of Health (Ministry of Health) have the goal to reduce the abortion rate in
      Greenland with 50% within the next 5 years. In spring 2003 an internal campaign
      was carried out in 8 communities/hospitals: Ittoqqortoormiit, Upernavik,
      Ilulissat, Aasiaat, Maniitsoq, Paamiut, Narsaq and Qaqortoq. The aim of the
      campaign was to recognize the problems and wishes for the future effort from the
      perspective of professionals (health professionals, teachers, preventive
      workers). STUDY DESIGN: Descriptive analyses of possibilities and barriers among
      professionals and lay people. METHODS: Participating observations, individual and
      group interviews. RESULTS: Though there are local variations, many problems are
      identical in the different communities. The general problems are related to
      collaboration, sexual supervision, education and mediation, contraceptive
      methods, access to contraceptive methods and moral standards in communities and
      the society in general. CONCLUSION: Increased collaboration between
      professionals, lay people and key persons in the community; improved quality and
      focus on sexual education; awareness on contraceptive methods used; new
      strategies in access to (desirable) condoms and increased focus on the problems
      related to unwanted pregnancies in society.

PMID- 15736664
TI  - Trends in the dietary patterns and prevalence of obesity among Greenlandic school
      children.
AB  - OBJECTIVE: The aim of the study was to examine the trends in the dietary patterns
      of selected food items and in the prevalence of self-perceived obesity in a
      population of Greenlandic schoolchildren. STUDY DESIGN: The study is based on
      three school surveys among Greenlandic schoolchildren, class 6 to 11 in public
      schools, and contributing to the Health Behaviour in School-aged Children (HBSC)
      Study. Data are collected through self-completed questionnaires administered in
      the classroom. Three surveys have been carried out in Greenland in 1994, 1998 and
      2002 with the participation of 2,999, 3,057 and 2,010 pupils, respectively.
      RESULTS: The intake of vegetables has increased significantly since 1994, and the
      intake of fruits, sweets and soft drink has decreased significantly at a 5%
      level. An unchanged high proportion of schoolchildren report to be on a diet or
      consider themselves obese. CONCLUSION: Most of the observed trends are positive,
      with regard to intake of vegetables and sweets and consumption of soft drinks.
      The fact that a high proportion of schoolchildren consider themselves to be obese
      must be assumed to have a negative impact on the psychological well-being of this
      population. The results of the survey can reveal changes which have occurred over
      time for the specified population. This knowledge can be used in public health
      work and planning.

PMID- 15736666
TI  - Youth sexual health in Nunavut: a needs-based survey of knowledge, attitudes and
      behaviour.
AB  - OBJECTIVES: This study attempts to address the need for culturally specific data
      on beliefs and behaviours in order to design and implement appropriate public
      health interventions. The goal of the health promotion booklet that followed the
      study is to give youth a tool that will promote healthy choices and give non
      judgmental information about sexuality. STUDY DESIGN AND METHODS: Knowledge gaps
      and beliefs about birth control, healthy sexuality and sexual health education
      were assessed through a written survey of young adults in three schools on Baffin
      Island. The sexual health survey was four pages long and written in simple
      language. The survey was voluntary, consensual and confidential, and it was
      administered by teachers. RESULTS: Some of the findings from the Iqaluit high
      school student survey (n=71) are reported with references to results from a
      smaller Iqaluit college student group (n=31). CONCLUSIONS: In Nunavut, teen
      pregnancy and sexually transmitted infection rates exceed national averages and
      continue to have devastating health and social consequences--particularly for
      Inuit girls and women. Using the data and a participatory approach, a culturally
      appropriate, bilingual booklet about sexual health is being developed for Nunavut
      youth.

PMID- 15736667
TI  - Adolescent mothers: a challenge for First Nations.
AB  - OBJECTIVES: Adolescent pregnancy is a growing Public Health problem in Greenland,
      resulting in higher risk of mortality of mothers and their children. Since social
      and cultural aspects are associated with adolescent pregnancy, a closer look was
      taken at the situation of adolescent mothers in Greenland and in Native American
      communities. METHODS AND RESULTS: Adolescent pregnancies and birth rates were
      followed in Greenland and in the First Nation communities in Alaska. Adolescent
      pregnancies decreased during the 1990s in both communities, but increased in
      2000, bringing up the birth rate to 79 and 92 babies per 1,000 girls aged 15-19
      yrs in Greenland in the U.S., respectively. CONCLUSIONS: A mentoring program to
      delay adolescent pregnancy and parenting, shown to be effective in African
      American and Latino communities, could be also used in the Greenlandic setting.

PMID- 15736668
TI  - Feasibility of Dual-Energy X-ray Absorptiometry in Arctic field studies.
AB  - BACKGROUND: Bone strength decreases with age. Bone mineral density (BMD) is a
      measure of bone strength. Data on BMD in present-day Inuit are limited, and data
      on circumpolar populations using Dual Energy X-ray Absorptiometry (DEXA scanning)
      are lacking. OBJECTIVES: Our aims were to validate DEXA scanning for use in field
      studies in the Arctic region and to obtain data on BMD in Greenland Inuit.
      METHODS: We measured BMD in 52 healthy Inuit living in Ilulissat and Saqqaq in
      North Greenland using a portable peripheral DEXA scanner. The measurement sites
      were forearms and calcaneal bones. Two measurements were performed at both radii
      and both calcanei. Triplicate measurements were performed in eleven Inuit.
      RESULTS: The portable scanner fitted into a standard bag suitable for
      transportation in the arctic winter. Imprecision was well within 2% for all
      calibrations. CV% were 0.16% to 1.79% in the forearms and 0.38% to 1.53% in the
      heels. The overall CV% was 1.09% in forearm and 1.01% in heel. Mean BMD in men
      was 0.569 g/cm2 in forearms and 0.542 in heel. In women it was 0.479 in forearms
      and 0.468 in heel. CONCLUSION: DEXA scanning is a feasible, reliable and
      comfortable method in rural Greenland. BMD values are now available for Greenland
      Inuit.

PMID- 15736669
TI  - Risk factors for ischaemic stroke in young Greenlanders.
AB  - INTRODUCTION: Contrary to a widely held belief, ischaemic cerebral infarction is
      not a rare disease in Greenland, as shown recently by our institution. We report
      data on some of the known risk factors in patients below 60 years of age with
      ischaemic stroke. METHOD: Retrospective data collection and review of charts from
      Greenlandic patients from all of Greenland admitted to the central hospital,
      Dronning Ingrids Hospital in Nuuk, in the years 2001 and 2002. RESULTS: A total
      of 37 patients below 60 years of age were discharged with a diagnosis of cerebral
      infarction. All had a CT, which showed infarction in 32. Five were reported
      normal, and the diagnosis of infarction rested on the absence of haemorrhage
      combined with long-standing, major neurological defect. Median age of the group
      was 54 years. Fifteen (40%) were women, thirty (81%) were smokers. Nine (24%) had
      hypertension. Two had diabetes, one had atrial fibrillation, and one had dilated
      cardiomyopathy. Two had significant carotid atherosclerosis diagnosed by duplex
      ultrasound. Of the rest, fifteen had transoesophageal echocardiography done,
      thirteen of which showed atherosclerotic changes. The cholesterol levels showed
      relatively high HDL levels. CONCLUSION: Ischaemic stroke is a common disease in
      young Greenlanders and seems to be associated with atherosclerosis with smoking
      as the only outstanding risk factor--though not more common than in the general
      population.

PMID- 15736670
TI  - Incidence of myocardial and cerebral infarction in Nuuk, Greenland.
AB  - INTRODUCTION: Myocardial and cerebral infarction are held to be rare among the
      Inuit, whereas cerebral haemorrhage is thought to be frequent. Recent studies
      have questioned these beliefs. We report data form our institution. METHOD:
      Retrospective data collection and review of all charts from Greenlandic patients
      from the Nuuk area admitted to the city hospital, Dronning Ingrids Hospital, from
      1999 to 2002. RESULTS: A total of 8 patients with myocardial infarction were
      found, median age 70 years, 4 with ST elevation MI and 4 with non-ST elevation
      MI. Two of the former had thrombolysis. Thirty-five patients were admitted with
      stroke, excluding subarachnoid haemorrhage, median age 65 years. Of these, twenty
      nine had a CT. Five scans were reported as being normal, one patient had an
      intracerebral haemorrhage and twenty-three had cerebral infarctions. Six had no
      CT. One of these was admitted comatose and died without regaining consciousness,
      the rest were minor strokes in patients over 70. CONCLUSION: Myocardial
      infarction is a rare disease in Greenlanders, whereas stroke is four times as
      frequent. The overwhelming majority of strokes are infarctions, whereas
      intracerebral haemorrhage seems to account only for a small minority.

PMID- 15736671
TI  - Risk factors for cardiovascular diseases among Swedish Sami--a controlled cohort
      study.
AB  - OBJECTIVE: To investigate the occurrence of clinical, psychosocial and
      behavioural risk factors for cardiovascular diseases (CVD) among reindeer herding
      (RS) and non-reindeer herding Sami (NRS). STUDY DESIGN: A retrospective cohort
      study, comparing risk factors behind CVD between Sami and non-Sami, RS and NRS,
      and Sami men and women. METHODS: A cohort of 611 Swedish Sami (276 men and 335
      women) was constructed from national population registers. A twice as large
      control cohort of non-Sami was created, matched by age, gender and area of
      residence. Information on risk factors was obtained from a database containing
      clinical and psychosocial-behavioural data from a regional CVD preventive
      programme for the period 1990-2001. RESULTS: The Sami and the non-Sami showed
      similar risk factor patterns. The main differences were related to working
      conditions and lifestyle factors of the RS. The RS men had lower blood pressure,
      were more physically active and had higher job demand and decision latitude. The
      RS women showed more negative scores on the indices of the job strain model.
      CONCLUSIONS: Previously reported differences in CVD mortality between Sami and
      non-Sami, and Sami men and women, can only partly be explained by different
      exposure to the psychosocial and behaviour risk factors investigated in this
      study.

PMID- 15736672
TI  - Very high concentrations of n-3 fatty acids in peri- and postmenopausal Inuit
      women from Greenland.
AB  - OBJECTIVES: The objectives of this study were to examine the profile of relative
      concentrations in plasma phospholipids of n-3 fatty acids among peri- and
      postmenopausal Inuit women living in Greenland and to verify their relationships
      with ischemic heart disease risk factors and more particularly, with
      concentrations of plasma triacylglycerols. STUDY DESIGN: This study was part of a
      survey conducted in 2000, which aimed to assess the prevalence of osteoporosis
      and the associated risk factors among peri- and postmenopausal Greenland Inuit
      women. METHODS: The study population consisted of 153 women aged 49-69 years
      (mean +/- SD: 55.3 +/- 4.4 y) randomly selected. Data were obtained through an
      interview (questionnaire on lifestyle habits, medical history etc) and a clinical
      session (physiologic and anthropologic measurements). Plasma samples were used to
      measure the fatty acid composition of plasma phospholipids. RESULTS: The mean
      body mass index of women was 27.9 +/- 6.1. Seventy-five percent were smokers and
      9% were currently on hormone replacement therapy. Relative concentrations of
      total n-3 fatty acids were very high (13.8%, 95% CI: 13.1-14.6), with
      docosahexanoic and eicosapentanoic acids accounting for 4.7% and 7.2%,
      respectively. The ratio of n-3:n-6 fatty acids was 0.67. n-3 fatty acids were
      inversely correlated to triacylglycerols. CONCLUSION: These data show that peri-
      and post-menopausal Greenland Inuit women have very high plasma concentrations of
      n-3 fatty acids that protect them from ischemic heart disease.

PMID- 15736673
TI  - Chronobiological and morphofunctional aspects of arterial hypertension under
      circumpolar conditions.
AB  - INTRODUCTION: Nowadays the problem of population health in the northern areas is
      of great importance. While evaluating human adaptation to the extreme
      geoecological northern conditions the state of the cardiovascular system can be
      used as an index of effective compensatory adaptation. STUDY DESIGN: The data on
      24-hour BP monitoring, data of echocardiography and heliogeophysical factors in
      different periods of ontogenesis in 317 patients, living in the north of the
      Tyumen region, were analysed to estimate the morphofunctional and
      chronobiological peculiarities of arterial hypertension. RESULTS: Considerable
      disorders of haemodynamic circadian rhythms, manifesting either insufficient
      decrease of BP at night are revealed in the examined subjects. Above 42.2% of
      such patients have myocardial hypertrophy. Insufficient night decrease of BP is
      typical for the examined patients, with coupling of the indices of haemodynamic
      and current geomagnetic activity. The peculiarities of heliogeophysical factors
      at early ontogenesis of the examined subjects with an increased variability and
      decreased circadian index of BP are defined using multivariate analysis.
      CONCLUSION: Thus, a combination of disorders of temporary haemodynamic
      organisation with the morphological changes of myocardium and peculiarities of
      biogeophysical coupling of the examined is shown. This anthropoecological
      approach can be used for the diagnostics and treatment of arterial hypertension
      under conditions of the northern ecosystem.

PMID- 15736674
TI  - Hearing screening outcomes in Inuit children in Nunavik, Quebec, Canada.
AB  - OBJECTIVES: Hearing loss is highly prevalent among Inuit children in Canada.
      Hearing screening at kindergarten age has been carried out in Nunavik by trained
      Inuit technicians since 1986. In this study, we determined what percentage of
      children fail their initial hearing screening at age 5-6 years and compared this
      initial result with the last hearing test. We also report the type of hearing
      loss observed at the last test. METHODS: Results compiled in a clinical database
      were analysed. At age 5-6 years, 524 children (born 1990-1994, 84% coverage) were
      tested and 515 children were retested at a later date. Screening failure was
      defined as >22 dB pure tone average (.5k, 1k, 2kHz) in either ear. Observations
      on ear condition at the last test were used to determine type of hearing loss.
      RESULTS: Nineteen percent (101 children) failed the hearing screening at age 5-6
      years and 12% failed on the later test. When those who failed the first test were
      retested, 58 had improved and 43 remained with a hearing loss. Twenty-one
      children who had initially passed the hearing screening were found to have a
      hearing loss at retest. The majority of the hearing losses were due to otitis
      media. CONCLUSION: Hearing screening and retesting remains necessary due to the
      high prevalence of hearing loss found in this population and the fluctuating
      nature of this problem.

PMID- 15736675
TI  - Otitis media and hearing loss among 12-16-year-old Inuit of Inukjuak, Quebec,
      Canada.
AB  - OBJECTIVES: Chronic otitis media (COM) and associated hearing loss is a frequent
      problem for many Inuit children in Canada. In this study, we evaluated
      individuals aged 12-16 years living in Inukjuak, to determine the prevalence of
      middle ear disease and hearing loss, and the effect of hearing loss on academic
      performance. METHODS: Otological examination, hearing test, medical and school
      file review were performed in November 1997. 88 individuals were seen. RESULTS:
      Otological examination revealed maximal scarring in 1.8%, minimal scarring in
      34.9%, normal eardrums in 49.1% and chronic otitis media in 16.9%. There were 62
      individuals whose ear exams could be directly compared with a previous exam done
      in 1987. Of those, there were three ears that had developed COM and 4/13 ears
      with COM in 1987 that had healed. Hearing tests found bilateral normal hearing in
      80% (PTA <20dB), unilateral loss in 15% and bilateral loss in 5%. Hearing loss
      was associated with poorer academic performance in Language (p<.05). A similar
      trend was found in Mathematics but not in Inuttitut. CONCLUSION: Chronic otitis
      media remains a significant problem among the Inuit, with a prevalence of 16.9%
      in individuals aged 12-16 years. One in five in this age group has hearing loss,
      and this hearing loss impacts on academic performance.

PMID- 15736676
TI  - Strategy for decentralised prevention of angle closure glaucoma in Greenland.
AB  - In 1962 a blindness survey showed glaucomas to be responsible for 64% of all
      blindness in Greenland. In 1968 primary angle closure glaucoma was found to be
      the major glaucoma problem. Population studies using gonioscopy, optical anterior
      chamber depth, corneal thickness, diameter- and curvature measurements as well as
      ultrasound biometry were gradually performed. Prevalence was estimated at 5.1% in
      women and 1.6% in men aged 40+. Main findings were eye traits associated with
      increased risk of angle closure glaucoma: shallow anterior chamber depth and
      small corneal diameters. A high heritability (70%) was found. Surgical
      iridectomies and later YAG-laser iridotomies were introduced as routine
      procedures by travelling consultants and at the referral centre Rigshospitalet in
      Copenhagen. Eventually, in 1993-96 a surgical eye clinic was established in the
      capital Nuuk, also introducing phakoemulsification cataract surgery. Blindness
      due to glaucomas had fallen to about 9% of the registrations in Greenland per
      1999. In 1999 an outreach model had to be established again, including
      consultants covering the 16 districts in 45 weeks and surgical teams of 2
      surgeons 3 x 3 weeks per year. In 2002 the coverage was reduced to 31 weeks and
      only two surgical tours.--The possible consequences for glaucoma blindness will
      be discussed.

PMID- 15736677
TI  - Age-related macular degeneration among the Inuit in Greenland.
AB  - OBJECTIVES: To investigate the clinical appearance and prevalence of Age-related
      Macular Degeneration (AMD) among the Inuit in Greenland, to investigate risk
      factors and to initiate the search for possible genetic markers. STUDY DESIGN: A
      cross-sectional population study including all individuals older than 60 years of
      age, born in Greenland and living in the communities of Nuuk and Sisimiut, was
      performed in 2000 and 2001. METHODS: All participants underwent an ophthalmologic
      examination, which was complemented by fundus photography and a questionnaire.
      RESULTS: 689 individuals, or more than 70%, participated in the study. Data are
      currently being processed. The preliminary data suggest that AMD among the Inuit
      is characterised by a rather uniform morphology and poor visual outcome. The
      detection of more cases of AMD in the early and late stages in relation to
      intermediate stages furthermore indicates a rapid development of AMD among the
      Inuit. CONCLUSION: The relative homogeneity of the Inuit population of Greenland
      may represent an opportunity for identifying the aetiological factors responsible
      for the development of AMD. The future results of this research project will
      hopefully also contribute towards an increased focus on the growing number of
      individuals with visual impairment due to AMD among the Inuit.

PMID- 15736678
TI  - A political economy of oral health services in Nunavut.
AB  - OBJECTIVES: We wanted to consider what factors influence oral health care
      services and carried out an Ethnographic Case Study in Nunavut. METHODS:
      Participant observation, document review, stakeholder interviews. RESULTS: This
      study argues that four general factors influence oral health care in Nunavut.
      CONCLUSION: These factors delimit oral health and care in Nunavut by influencing
      people's oral health, their experiences with health and disease, and ultimately
      the positions and practices of individuals within this system of care. Thus these
      factors contribute to (or take away from) the ability for positive change in the
      oral health of Nunavut residents. It is in settling debates within the latter two
      factors that an appreciable difference can be made in the oral health and care of
      Nunavut residents.

PMID- 15736679
TI  - Prevalence of crab asthma in crab plant workers in Newfoundland and Labrador.
AB  - OBJECTIVES: The aim of the study was to determine the prevalence of snow crab
      sensitisation and occupational asthma. STUDY DESIGN: Prevalence study of
      symptoms, pulmonary function testing and allergy testing to crab was conducted in
      four crab plants of different design in Newfoundland and Labrador, Canada.
      METHODS: Plants workers in four crab plants were interviewed and offered skin
      testing, RAST, pulmonary function testing and peak flow monitoring before and
      during crab processing. RESULTS: 38% (n=78) had atopy. 18% (n=39) had certain or
      highly probable crab asthma. The prevalence of sensitisation in different crab
      plants varied from 50% (n=19) to 15% (n=16) and the prevalence of certain or
      highly probable crab asthma varied from 50% (n=19) to 9% (n=3). CONCLUSION: Crab
      asthma and sensitisation to snow crab is a major health problem for snow crab
      plant workers in Newfoundland and Labrador.

PMID- 15736680
TI  - Knowledge, attitudes and beliefs regarding crab asthma in four communities of
      Newfoundlad and Labrador.
AB  - OBJECTIVES: This study was conducted to learn from snow crab plants workers and
      others involved in the industry their knowledge and beliefs of health issues and
      potential solutions. STUDY DESIGN: This is a survey in four communities with
      different crab plant designs in Newfoundland and Labrador, Canada. METHODS: At
      the start of a meeting to discuss crab asthma participants were requested to
      complete the questionnaire. RESULTS: 65% of 196 participants believed there were
      health problems associated with crab plants. 85% have heard of crab asthma.
      Almost 80% identified correctly the major symptoms of crab asthma as difficulty
      breathing, chest tightness and cough. Only 74% of workers did not know that
      workers with crab asthma were eligible for workers' compensation. 55% of those
      surveyed had heard of crab asthma from crab plant workers and only 26% from their
      doctor or nurse. If they had breathing problems, 73% would see their local
      doctor, and 51% a specialist and 51% their nurse. CONCLUSION: The majority of
      participants believed that there were health problems associated with crab
      plants. The majority of crab plant workers could identify symptoms of crab asthma
      correctly. Many do not know that those with crab asthma can obtain workers'
      compensation. Most of them learn of crab asthma from other workers but would seek
      treatment from their doctor.

PMID- 15736681
TI  - Work-related musculoskeletal pain among reindeer herding Sami in Sweden--a pilot
      study on causes and prevention.
AB  - OBJECTIVE: To investigate the prevalence and to identify causes of
      musculoskeletal pain (MSP) among reindeer herding Sami, and to evaluate the
      impact on the MSP symptoms elicited by an intervention-prevention programme (IP
      programme). STUDY DESIGN: A prospective cohort study in which alterations in MSP
      symptoms were documented over a two-year period. METHODS: Data were collected
      from 51 reindeer herders (26 men, 25 women) before and after a two-year IP
      programme. Information on MSP characteristics (affected body regions, pain
      duration and pain intensity) and exposure to a number of physical and
      psychosocial risk factors were collected as part of comprehensive health
      examinations. Clinical examinations and interviews complemented self-reported
      data collected through questionnaires. RESULTS: MSP symptoms were prevalent, both
      among women and men. High exposure to physical risk factors, to a large extent
      related to extensive use of snowmobiles and motorcycles, was the main cause of
      MSP among men, while psychosocial risk factors were suggested to be more
      important among women. About one-third of the reindeer herders reported fewer MSP
      symptoms as a result of the IP programme. CONCLUSIONS: This pilot study suggests
      that it is possible to reduce the number and the severity of the MSP symptoms
      among reindeer herders by implementing suitably tailored intervention-prevention
      measures.

PMID- 15736682
TI  - Estimation of functional state and labour efficiency of shift workers in
      conditions of the Far North.
AB  - OBJECTIVES: Shift work is an expeditionary method, and it has become quite common
      for the maintenance of industrial process in the Far North. In spite of good
      equipment and a high professional standard of the medical personnel in the
      majority of northern enterprises, the level of morbidity tends to increase. The
      aims of our work were to evaluate the psychophysiological alterations in shift
      workers during transit labour. METHODS: Shift workers of "Gazprom" Public
      Corporation were examined in conditions of the Far North using psychological and
      physiological methods. RESULTS: The morbidity of shift workers is higher than
      that of non-transit workers working in the same industries. Distinct changes of
      the functional condition of the cardiorespiratory system were discovered. While
      comparing shift workers of the Far North with workers of the Central regions of
      Russia we discovered an essential prevalence of isolated systolic hypertension
      (44.6%) in the first group. It is established that an increase of anxiety level
      (situational and personal) is much more common in persons having haemodynamic
      signs of hypertension. For workers in intraregional shift work metabolic exchange
      disorders, and for workers in inter-regional shift disorders of immune resistance
      are typical. CONCLUSIONS: Our results have shown that shift work is accompanied
      by stress of regulatory and adaptable systems, a decrease of functional reserves
      and an increased morbidity and frequent relapses.

PMID- 15736683
TI  - Scientific worker and licensed professional deaths in Alaska, 1990-2002.
AB  - OBJECTIVES: Between 1990-2002, 797 Alaskans died while working. After a
      scientific survey team member drowned, we examined the hazards of traumatic death
      to scientific and professional workers in Alaska. STUDY DESIGN: Surveillance and
      analysis methods for acute traumatic occupational injuries: The Alaska
      Occupational Injury Surveillance System (AOISS) uses direct investigation,
      jurisdictional agency reports, and death certificates to gather data for active
      surveillance on occupational injury deaths in Alaska. We searched AOISS for
      deaths which occurred while engaged in scientific or professional work.
      Commercial pilots, fishermen, loggers, taxi drivers and miners were excluded, as
      these have been previously studied. RESULTS: During 1990-2002, 85
      scientific/professional worker deaths (including 2 suicides) occurred. Fish,
      game, and mountaineering guides accounted for 28 (33%) of the worker deaths,
      followed by biologists, who accounted for 11 (13%). Aircraft crashes accounted
      for 42 (49%) of all these deaths, followed by drownings, 12 (14%), and falls, 9
      (11%). A seismologist was fatally mauled by a bear. Of the 14 hunting guide
      fatalities, 11 were the result of aircraft crashes, one was a suicide, one was a
      drowning, and one resulted from a motor vehicle crash. Of the 11 hunting guide
      fatalities, eight died in aircraft crashes, one drowned, one walked into an
      aircraft prop, and one sustained a fatal head injury in a fall. CONCLUSIONS:
      Scientific and professional workers in Alaska experienced a substantial number of
      fatalities from traumatic injury. Nearly half of these deaths occurred in
      aircraft crashes.

PMID- 15736684
TI  - The role of hypothermia and drowning in commercial fishing deaths in Alaska, 1990
      2002.
AB  - OBJECTIVES: To describe the patterns associated with cold-water immersion and
      drowning in commercial fishermen in Alaska from 1990 through 2002. STUDY DESIGN:
      This is a retrospective study using data from the Alaska Occupational
      Surveillance System (AOISS), a database with records from all occupational
      mortalities occurring in Alaska from 1990 on. METHODS: We extracted and analyzed
      all records describing deaths from drowning or hypothermia to commercial
      fishermen in Alaska from 1990 through 2002 that were registered within AOISS. We
      also used a subset of records from AOISS to compare use of Personal Flotation
      Devices (PFDs) between the target population and survivors of fatal events.
      RESULTS: There were 228 deaths resulting from cold-water immersion and subsequent
      drowning in the target population for the time period studied. Victims were far
      less likely to have used PFDs than were survivors of events where cold-water
      drowning occurred. CONCLUSION: The strong protective association seen with the
      use of PFDs, particularly immersion suits, in surviving cold-water events
      indicates that many of the events that led to deaths in the target population
      could well have been survivable.

PMID- 15736685
TI  - Epilepsy among children in Greenland.
AB  - INTRODUCTION: Epilepsy has been considered to be more frequent in Greenland than
      in Denmark, where the prevalence among children is 0.40%. STUDY DESIGN:
      Evaluation of the prevalence, diagnosis and treatment of epilepsy among children
      in Greenland aged 0-15 years. METHODS: During autumn 2000, 13 out of 18 hospitals
      in Greenland were visited. The population of children in the areas visited was
      11,965 of a total of 15,226 in Greenland. All children with the diagnosis of
      epilepsy were referred for evaluation and the diagnosis was confirmed. When
      possible, informed consent was obtained to collect data from medical records.
      RESULTS: 43 children (18 boys) had the diagnosis of epilepsy. For 38 (15 boys)
      further data were obtained. Mean age was 8.5 years (3-14) for boys and 7.9 years
      (2-14) for girls. The age at diagnosis was 4.9 years (1-11) for boys and 4.2
      years (0-10) for girls. The prevalence of epilepsy was 0.34%. In 31 cases an
      electroencephalograph (EEG) recording was done, comprising sleep recordings in 26
      cases. Medication was according to recommendations in Denmark. CONCLUSION: The
      prevalence of epilepsy in children and the medical treatment of epilepsy among
      children in Greenland is the same as in Denmark.

PMID- 15736686
TI  - Parkinson's disease among Inuit in Greenland: organochlorines as risk factors.
AB  - OBJECTIVES: In the present study we investigate organochlorines as possible risk
      factors for Parkinson's disease (PD) in an arctic population. This has never been
      done before. STUDY DESIGN: Case-control study of Inuit in Greenland. MATERIALS
      AND METHODS: Plasma from 31 PD (20 males and 11 females) (mean age 69 yr) and 122
      controls (57 males and 65 females) (mean age 61 yr) was analysed for 31 PCBs and
      pesticides by dual-column GC-ECD and GC-NCI/MS. RESULTS: Plasma concentrations of
      PCBs and pesticides were markedly increased in both PD and controls. The
      concentrations did not differ between the PD cases and controls. However, the
      mean DDE concentration was higher in PD than in controls (42.1 and 15.0 microg/l,
      respectively, and with a wide range among the PD cases). The difference was
      significant for log transformed DDE values after control for age and sex
      (p=0.005). CONCLUSION: A few epidemiological studies indicate a possible
      connection between exposure to pesticides and PD. The idea that exposure to
      organochlorines may be an important risk factor for PD among the Inuit in
      Greenland requires more investigations.

PMID- 15736687
TI  - High age-adjusted prevalence of Parkinson's disease among Inuit in Greenland.

PMID- 15736688
TI  - Acculturation and mental health--empirical verification of J.W. Berry's model of
      acculturative stress.
AB  - OBJECTIVES: Many studies concerning mental health among ethnic minorities have
      used the concept of acculturation as a model of explanation, in particular J.W.
      Berry's model of acculturative stress. But Berry's theory has only been
      empirically verified few times. The aims of the study were to examine whether
      Berry's hypothesis about the connection between acculturation and mental health
      can be empirically verified for Greenlanders living in Denmark and to analyse
      whether acculturation plays a significant role for mental health among
      Greenlanders living in Denmark. STUDY DESIGN AND METHODS: The study used data
      from the 1999 Health Profile for Greenlanders in Denmark. As measure of mental
      health we applied the General Health Questionnaire (GHQ-12). Acculturation was
      assessed from answers to questions about how the respondents value the fact that
      children maintain their traditional cultural identity as Greenlander and how well
      the respondents speak Greenlandic and Danish. The statistical methods included
      binary logistic regression. RESULTS: We found no connection between Berry's
      definition of acculturation and mental health among Greenlanders in Denmark. On
      the other hand, our findings showed a significant relation between mental health
      and gender, age, marital position, occupation and long-term illness. CONCLUSION:
      The findings indicate that acculturation in the way Berry defines it plays a
      lesser role for mental health among Greenlanders in Denmark than socio
      demographic and socio-economic factors. Therefore we cannot empirically verify
      Berry's hypothesis.

PMID- 15736689
TI  - Common mental disorders among patients in primary health care in Greenland.
AB  - INTRODUCTION: There are many indications that mental health in Greenland is
      endangered and needs more attention. STUDY DESIGN: A two-stage study of the
      prevalence of common mental disorders among a sample of primary health care
      patients. METHODS: 376 randomly selected patients from general consultations in
      two Greenlandic towns were screened with 12 questions from the General Health
      Questionnaire. From these patients, a sample of 100 patients, including more high
      than low-scorers, was interviewed using the SCAN (Schedules for Clinical
      Assessment in Neuropsychiatry) Present Examination psychiatric interview.
      RESULTS: Estimated prevalence for the total study population of at least one
      psychiatric diagnosis was 49.3% (95% CI 39.7-59.0%). Most diagnoses were in the
      group of anxieties, somatoform disorders and depressive disorders. Many patients
      had more than one diagnosis. Lack of education and poor proficiency in Danish, as
      well as growing up in a family with severe alcohol problems, were high risk
      factors for a psychiatric diagnosis. Patients and physicians seemingly agreed on
      focusing on physical disorders at the consultation, and only a minority of mental
      disorders was recognised and treated as such by the physicians. CONCLUSION:
      Mental disorders are prevalent but not sufficiently recognised and treated among
      patients in primary health care in Greenland. Their association with social and
      economic conditions calls for attention from the health services as well as from
      social and educational institutions.

PMID- 15736690
TI  - Fatal accidents and suicide among reindeer-herding Sami in Sweden.
AB  - OBJECTIVE: Over the last decades, reindeer-herding management has experienced
      dramatic changes, e.g. increased motorization and socio-economic pressure. The
      aim of the present study was to investigate whether these changes have increased
      the risk of fatal, work-related accidents and suicide between 1961 and 2000.
      STUDY DESIGN AND METHODS: A cohort containing 7,482 members of reindeer-herding
      Sami families was extracted from national population registers. Information on
      fatal accidents and suicide was obtained from the Swedish Causes of Death
      Register, and compared to the expected number of deaths in a demographically
      matched control population of non-Sami. RESULTS: The male reindeer herding Sami
      showed a significantly increased risk of dying from accidents such as vehicle
      accidents and poisoning. No significant increased risk of suicide was observed. A
      comparison between the periods of 1961-1980 and 1981-2000 showed non-significant
      differences in risk, although a trend towards increased risks was observed for
      most types of external causes of death except suicide. CONCLUSIONS: It is
      suggested that the increased socio-economic pressure and the extensive use of
      terrain vehicles have increased the risk for fatal accidents among Swedish
      reindeer herders, and that commercial reindeer management is one of the most
      dangerous occupations in Sweden.

PMID- 15736691
TI  - Can we compare violence data across countries?
AB  - OBJECTIVES: The paper aims to explore what knowledge can be obtained about
      violence through population-based data and additionally, through inter-country
      comparisons of violence data. STUDY DESIGN AND METHODS: Data on lifetime and 12
      month experiences of violence and/or severe threats of violence were obtained
      from self-administered questionnaires supplementary to nationwide, cross
      sectional health interview surveys conducted in Greenland in 1993-94 (N=2,425)
      and in Denmark in 2000 (N=16,684). The overall response rate achieved for the
      self-administered questionnaire was 63% (N=1,393) in Greenland and 63% (N=10,458)
      in Denmark. RESULTS: A comparison of violence data shows that overall, the
      violence prevalence was significantly higher in Greenland than Denmark.
      Experienced violence and/or severe threats amongst Greenlandic women was almost
      as prevalent as amongst Greenlandic men--especially so for severe lifetime
      violence. This was not the case for the Danish sample. Significantly more Danish
      men than Danish women reported experienced violence and/or severe threats for all
      age groups. CONCLUSION: Comparing violence data across countries enables us to
      describe actual differences in violence prevalence, as well as to highlight
      potential methodological discrepancies and cultural and gender differences in
      understanding and, thus, reporting of violence. This knowledge can be implemented
      in the development and improvement of existing and new prevention strategies.

PMID- 15736692
TI  - Reorganization of perinatal care in Greenland.
AB  - INTRODUCTION: September 2000 the planning of a major reform of health services
      was launched aimed at improving perinatal care and decreasing perinatal mortality
      and morbidity. The activities became effective from January 2002. METHODS: A new
      organization plan was developed, a special medical record was designed for
      perinatal care and training programs for health workers in perinatal care were
      instituted, including basic ultrasound scan for gestational age. Professional
      guidelines for perinatal care were distributed countrywide, stipulating that at
      risk pregnancies should be referred for delivery to Queen Ingrid's Hospital, as
      well as offering treatment suggestions for various complications. RESULTS: There
      was a marked improvement in the referral rate for at risk pregnancies and
      consequently a sharp rise in the share of at risk patients in Queen Ingrid's
      Hospital, calling for extra resources to be allocated. However, the rate for
      instrumental deliveries remained low at the special unit at the same time as the
      rural health care centres were relieved of the burden of high-risk deliveries.
      DISCUSSION: Transferring women for delivery, in many cases leaving their families
      for a substantial amount of time, undoubtedly has psychosocial implications. Will
      the impact of the programme on perinatal mortality and morbidity make up for
      these costs? Will we be able to reduce the rate of instrumental deliveries in the
      rural health care centres as well as the number of acute--and very costly-
      evacuations of patients by chartered aircraft? The questions are many--we hope to
      provide some answers.

PMID- 15736693
TI  - Experiences of sexual violence and relocation in the lives of HIV infected
      Canadian women.
AB  - OBJECTIVES: To investigate the role, if any, that violence and physical
      relocation may play in the acquisition of HIV infection in Canadian women. STUDY
      DESIGN: The present study is qualitative. METHODS: Using in-depth open-ended
      interviews conducted among HIV-positive women volunteers as a method. RESULTS:
      Twenty women were interviewed. Eighteen of the 20 were of aboriginal (First
      Nations) ethnicity. All participants reported experiences of isolation and
      violence in childhood (sexual abuse, domestic violence, emotional abuse). Half of
      those who experienced childhood sexual abuse reported being afraid to disclose
      the events to adults at the time due to fear of reprisal and/or shame. The
      majority reported running away from home to escape violence, with subsequent
      involvement in the sex trade and drug abuse as economic and emotional
      survival/coping strategies. Half reported previous incarceration in jail. The
      majority reported that they currently looked to community social programs for
      guidance and support. CONCLUSION: Early intervention programs must be implemented
      in partnership with communities to reduce family violence and create support
      networks for children, youth and adults at risk.

PMID- 15736694
TI  - Tobacco smoking status among Aboriginal youth.
AB  - OBJECTIVE: To determine what factors are associated with the smoking status among
      some of the spectators and participants of the 2002 North American Indigenous
      Games. STUDY DESIGN: Cross-sectional. METHODS: A survey inquiring about tobacco
      use and lifestyle behaviours was implemented at the North American Indigenous
      Games in Winnipeg, Canada. This survey, entitled the 2002 Aboriginal Youth
      Lifestyle Survey, included Aboriginal youth between the ages 12 to 22 years old.
      RESULTS: There were 570 survey participants (53.5% female) that met the inclusion
      criteria. It was determined that smoking initiation began earlier than what is
      reported in the literature and did not occur beyond age 18. The logistic
      regression analysis revealed that the variables age,peer smokings, self-rated
      health, and participation status at the NAIG, were associated with smoking status
      in this sample. CONCLUSION: These findings demonstrate that Aboriginal youth
      require different tobacco control strategies compared to non-Aboriginal youth.
      While these youth experience similar risk factors associated with smoking status,
      based on the earlier initiation age, tobacco prevention needs to commence much
      earlier. This study also showcases the positive role that involvement in physical
      activity plays in building resiliency among Aboriginal youth.

PMID- 15736695
TI  - Alcohol and other drug use among students in Greenland--a comparison between some
      1999 and 2003 ESPAD data.
AB  - OBJECTIVES: Smoking and drinking habits among young people are of great concern
      in Greenland. The Home Rule government has through the Department of Prevention
      (PAARISA) carried out several campaigns to highlight the risks of smoking and
      drinking alcohol. To monitor the changes in these habits Greenland has
      participated in the European Survey Project on Alcohol and Drugs (ESPAD) in 1999
      and 2003. The objective of this article is to make some preliminary comparisons
      between the 1999 and 2003 survey results on smoking and drinking alcohol. STUDY
      DESIGN/METHODS: The survey population in both the 1999 and 2003 surveys are all
      students in the 9th, 10th and 11th grade (persons between 14 and 16 years old).
      Hence the surveys include students born in 1982-84 and 1986-88, respectively. The
      ESPAD questionnaire focuses on alcohol and other drug use, but it also includes
      questions on lifestyle, relations to family and friends and the students'
      perception of their living conditions. Only answers from respondents born in 1983
      84 and 1987-88 and only questions on smoking and drinking habits are analysed in
      this article. RESULTS/CONCLUSION: Smoking and alcohol drinking among students
      aged 14-16 years has been decreasing from 1999 to 2003 measured by use during the
      last 30 days. The same trends cannot be found in students' use of
      marijuana/hashish and sniffing different substances.

PMID- 15736696
TI  - Prevalence and characterisation of Cryptosporidium species in cattle faeces and
      on beef carcases at slaughter.
AB  - Cattle are known reservoirs and asymptomatic excretors of Cryptosporidium, a
      protozoan parasite that causes severe and protracted diarrhoea in people. The
      incidence of Cryptosporidium was investigated in 288 matched samples taken from
      beef carcases of 1 g samples of faeces retrieved immediately after de-legging, 25
      cm2 samples of beef excised from the rump of uneviscerated carcases, and 25 cm2
      samples of beef excised from the brisket area of eviscerated carcases.
      Cryptosporidium species were detected in 21 of the faecal samples after salt
      flotation and immunofluorescent microscopy. The species isolated from the
      positive samples were identified by restriction fragment length polymorphism and
      PCR as Cryptosporidium andersoni (54.5 per cent) and Cryptosporidium parvum
      genotype 2 (45.5 per cent). In the faecal samples, there was a significantly
      higher prevalence of the parasite in samples taken in summer (May to July) and
      winter (November to January) than in spring or autumn. No Cryptosporidium species
      were recovered from any of the beef samples.

PMID- 15736697
TI  - Comparison of the efficacy of remote consultations and personal consultations for
      the treatment of dogs which are aggressive towards their owners.
AB  - Two groups of 42 dogs which were aggressive towards their owners were enrolled
      into a study designed to compare the efficacy of remote consultations with direct
      personal consultations for the treatment of the aggressive behaviour. The level
      of aggression of the dogs was assessed before and after programmes designed to
      modify their behaviour. Both programmes resulted in a significant reduction in
      the aggressive behaviour of the dogs towards their owners, and there was no
      significant difference between the effectiveness of the recommendations, whether
      they were made without having seen the dog or during a personal consultation with
      the dog and its owner.

PMID- 15736698
TI  - Outbreak of Mycobacterium tuberculosis infection among captive Asian elephants in
      a Swedish zoo.
AB  - Between 2001 and 2003, there was an outbreak of tuberculosis in a Swedish zoo
      which involved elephants, giraffes, rhinoceroses and buffaloes. Cultures of trunk
      lavages were used to detect infected elephants, tuberculin testing was used in
      the giraffes and buffaloes, and tracheal lavage and tuberculin testing were used
      in the rhinoceroses. The bacteria isolated were investigated by spoligotyping and
      restriction fragment length polymorphism. Five elephants and one giraffe were
      found to have been infected by four different strains of Mycobacterium
      tuberculosis.

PMID- 15736699
TI  - Effects of bovine somatotropin and timed embryo transfer on pregnancy rates in
      non-lactating cattle.

PMID- 15736700
TI  - Necrotising lymphadenitis associated with porcine circovirus type 2 in pigs.

PMID- 15736701
TI  - Cardiomegaly in a whooper swan (Cygnus cygnus).

PMID- 15736702
TI  - Application of a semitendinosus muscle flap in the treatment of perineal hernia
      in a cat.

PMID- 15736703
TI  - Periapical dental infection with nasolacrimal involvement in a horse.

PMID- 15736704
TI  - Extended-spectrum beta-lactamase detected in E coli recovered from calves in
      Wales.

PMID- 15736705
TI  - Prescribing veterinary medicines.

PMID- 15736706
TI  - RCVS Practice Standards Scheme.

PMID- 15736707
TI  - Out-of-hours cover.

PMID- 15736708
TI  - Out-of-hours cover.

PMID- 15736709
TI  - Out-of-hours cover.

PMID- 15736710
TI  - Cellular allergen stimulation test (CAST) 2003, a review.
AB  - Specific diagnosis of immediate type allergies, such as rhinoconjunctivis,
      asthma, urticaria/angioedema and anaphylaxis, particularly when IgE-mediated,
      traditionally rests on prick and/or intradermal skin tests and, since about 30
      years, on the determination of allergen specific IgEs. Some cellular tests, i.e.
      tests determining the reactivity of blood cells in vitro, particularly basophils,
      to allergens, have been available for many years. The determination of histamine
      release has been widely used in allergy pathophysiological research but its
      routine application in allergy diagnosis has been restricted to few groups.
      Basophil degranulation, as determined by microscopic examination, was promoted by
      some groups in the 1980's but has been largely abandoned since around 10 years
      ago; an alternative cellular test, based on the determination of
      sulfidoleukotrienes (LTC4, LTD4, LTE4) produced by IL-3 primed basophils
      stimulated by allergens in vitro, has been proposed. This test became available
      commercially in 1993 under the name of CAST (Buhlmann Laboratories, Allschwil,
      Switzerland). The CAST assay has been used in allergy diagnosis in a variety of
      indications, such as inhalation allergies, allergies to insect venoms, foods,
      occupational allergens and various drugs. A large number of reports on CAST
      diagnostic value, however, have been anecdotal. A meta-analysis of validated and
      well controlled studies encompasses 37 studies, 1614 patients and 1145 controls.
      This should definitely establish the value of this diagnostic test, particularly
      in instances where other in vitro or in vivo diagnostic tests are not reliable,
      such as food or drug allergies, as well as in non-IgE-mediated immediate
      hypersensitivity reactions. However, a number of questions about the CAST
      diagnostic assay are still open or have not been systematically explored. This
      may explain, in addition to the practical limitations inherent to all allergy
      cellular tests, why CAST has not yet become a very widely used assay worldwide,
      having gained broad acceptance in some countries but not in others.

PMID- 15736711
TI  - Continuing medical education. The point of view of asthmatic patients at the
      beginning of a mandatory CME system.
AB  - BACKGROUND: CME is well established in the USA and many European countries, but
      in Italy it became mandatory by law starting from 2002. The patient's opinion is
      a critical feedback signal for the outcomes of CME. We attempted, through a
      structured questionnaire, to evaluate the patient's opinion on CME a few months
      after its introduction. METHODS: A structured questionnaire involving 8 items
      concerning several aspects of CME was administered to asthmatic outpatients all
      over Italy. The questionnaire was anonymous and collected only demographic data.
      RESULTS: 298 questionnaires were eligible for analysis. One third of the patients
      were informed about the Health Ministery Law. 42% of patients indicated the
      update knowledge as the priority in CME, followed by communication with patients
      (14.09%) and attention to Quality of Life (13.09%). DISCUSSION: Independently of
      the Health Ministery Law knowledge, patients consider that the updating of
      knowledge has the priority in the professional development plan; the improvement
      of skills as communication with the patient and his family and the attention for
      Quality of Life, are recognized as more important than economical aspects of
      disease management.

PMID- 15736712
TI  - Basophil activation and sulfidoleukotriene production in patients with immediate
      allergy to betalactam antibiotics and negative skin tests.
AB  - BACKGROUND: New in vitro diagnostic methods for IgE-mediated drug allergic
      reactions, such as basophil activation test and antigen specific
      sulfidoleukotriene test, have proven their usefulness in patients with positive
      skin tests. OBJECTIVE: To assess the usefulness of basophil activation test and
      antigen specific sulfidoleukotriene test in the diagnosis of patients with IgE
      mediated allergy to Betalactam antibiotics and negative skin tests. METHODS: The
      23 patients included in the study underwent basophil activation test, antigen
      specific sulfidoleukotriene test and specific IgE. The patients were classified
      into three groups. GROUP A: patients with positive specific IgE. GROUP B:
      patients with a unique immediate reaction to Betalactams, negative specific IgE
      and positive oral provocation tests. And Group C: patients with at least two
      immediate reactions induced by Betalactams and negative specific IgE. RESULTS:
      The sensitivity/specificity of the different tests are: basophil activation test
      39.1 %/93.3%, antigen specific sulfidoleukotriene test 22.7%/83.3%, specific IgE
      21.7%/86.7%. The joint use of the three tests allows diagnosis of 60.9% of the
      patients. CONCLUSION: In vitro diagnostic tests, especially basophil activation
      test, are very important tools in the diagnosis of patients with IgE-mediated
      allergy to Betalactams and negative skin tests, avoiding performance of
      potentially dangerous oral provocation tests in a high percentage of cases.

PMID- 15736713
TI  - Clinical evaluation of response to long-term treatment with Pranlukast in
      patients with bronchial asthma.
AB  - BACKGROUND: Short-term treatment with pranlukast, a leukotriene receptor
      antagonist, has shown to be effective for the management of asthma. The
      effectiveness and safety of long-term treatment with pranlukast remains to be
      established. OBJECTIVES: The aim of this study was to determine the effects of
      pranlukast on morning peak expiratory flow rates (PEFRs), the diurnal variation
      of these values, and disease severity. METHODS: Fifteen men with bronchial asthma
      were studied for 5 years. During the first year, the subjects were treated with a
      bronchodilator; some also received inhaled and oral corticosteroids. During the
      next 4 years, the subjects received pranlukast in addition. RESULTS: Mean PEFR
      increased after the start of treatment with pranlukast. The increase in PEFR
      occurred later in subjects with more severe disease. Diurnal variation of PEFR
      was unchanged, but subsequently decreased. The condition of all subjects
      improved, but the greatest improvement was obtained in patients with mild to
      moderate asthma. CONCLUSIONS: Long-term treatment with pranlukast is effective
      for the management of bronchial asthma, particularly in patients with mild to
      moderate disease. Our results suggest that the effectiveness of antiasthmatic
      drugs should be evaluated over a period of years, rather than on a short-term
      basis.

PMID- 15736714
TI  - Low B12 levels in chronic idiopathic urticaria.
AB  - Recent studies suggest that autoimmune mechanisms may be involved in the etiology
      of chronic idiopathic urticaria (CIU). There is a higher prevalence of B12
      deficiency in autoimmune diseases and possibly in gastric Helicobacter pylori (H.
      pylori) infection. The frequency of B12 deficiency in CIU is unknown. Our
      objective in this study was to determine the prevalence of B12 deficiency in
      patients with CIU and also its relationship to gastric H. pylori infection and
      serologic markers of autoimmunity in these groups. Thirty-three patients with CIU
      and 27 healthy controls were included in the study. Serum vitamin B12 levels, H.
      pylori infection and serological markers of autoimmunity (anti-thyroglobulin,
      thyroid microsomal, gastric parietal cell and antinuclear autoantibodies) were
      investigated. H. pylori infection was determined according to serology and
      gastric biopsy in 19 patients, serology and urea breath test in 4 patients and
      serology alone in the remaining 10 patients. Serum B12 levels were below the
      normal reference range in 11/33 (33.3%) patients with CIU. The mean serum B12
      levels among patients with CIU and the controls were 281+/-127.5 pg/ml and
      465.1+/-140.3 pg/ml (p=0.0001), respectively. Anti-thyroid antibodies were
      positive in 6 of 11 patients (54.5%) with low B12 levels, but only in 4 of 27
      (14.8%) healthy controls (p=0.019). Anti-GPC antibodies were positive in 4 of 11
      (36.4%) patients with CIU and low B12 levels, but only in 2 of 27 (7.4%) healthy
      controls (p=0.047). In CIU patients, there was no difference in the frequency of
      IgG H. pylori antibodies between those with low B12 levels and normal B12 levels.
      Among the 19 patients who had been performed gastric endoscopy, 15 patients
      (78.9%) had chronic antral gastritis, 2 patients (10.5%) had atrophic gastritis
      and there were normal findings in 2 patients (10.5%). In conclusion, serum B12
      levels were found to be below the normal reference range in 33% of the patients
      with CIU. An association between low B12 levels and H. pylori could not be shown.
      The higher frequency of antithyroid and anti-GPC antibodies in patients with low
      B12 levels suggest that low B12 levels in CIU may be autoimmune in nature.

PMID- 15736716
TI  - Clinical features of patients showing Candida hypersensitivity: an observational
      study.
AB  - BACKGROUND: The significance of Candida albicans as an allergen is still unclear.
      This study aimed at investigating the clinical features of patients
      monosensitized to Candida. METHODS: Thirty-four adult patients monosensitized to
      the yeast Candida albicans selected from a population of >7000 subjects and
      referred for suspect respiratory allergy were studied. Ninety subjects
      monosensitized to different airborne allergens served as controls. Both patients
      and controls underwent a clinical examination at the ENT department to detect
      possible nasal polyps. RESULTS: Male and female patients were equally distributed
      (17/17). The mean age of the patients was 58.4 years (range 23-75 years; median
      59 years) vs 29.9 years (range 9-62 years) in controls (p <0.001). At baseline
      examination, 15 (44%) patients vs 5/90 (6%) controls were diagnosed as having
      nasal polyposis (p< 0.001). Polyposis was bilateral in 13/15 (87%) patients; 3
      had "massive" polyps, and 4 had a clinical history of prior surgical intervention
      to remove nasal polyps. Eight patients (24%) had asthma, previously diagnosed as
      intrinsic in six cases. No patient had a history of aspirin-induced asthma (i.e.
      ASA triad). After one year 1/11 (9%) patients without polyps at the baseline
      examination had developed bilateral nasal polyposis. CONCLUSION: Candida
      hypersensitivity is uncommon, occurs in older ages, and is strongly associated
      with nasal polyposis.

PMID- 15736715
TI  - Aerobiology as a tool to help in episodes of occupational allergy in work places.
AB  - Over 80% of weekday time is spent indoors and the air quality of this environment
      may affect the incidence of symptoms in allergy sufferers. However,
      indoor/outdoor measurements have been jointly considered only in a few studies.
      The objective of this paper is to analyse indoor/outdoor biological and non
      biological particle content togeher with other factors affecting the severity of
      symptoms during working periods in an Aerobiology Lab during the most troublesome
      period of the year for allergy sufferers. For this purpose, indoor/ outdoor air
      samples were taken using standard portable particle traps at the National
      Coordinating Centre of the Spanish Aerobiology Network, University of Cordoba.
      The analysis differentiated between biological and non-biological material, and
      the allergy symptoms suffered by workers were quantified and correlated
      accordingly. An inventory of the incoming and outgoing sources of emissions was
      done in order to identify agravating co-factors. The results showed that since
      there was very little air movement between indoors and outdoors, there was a
      significant difference in the amount of biological material present in the two
      areas. The presence of some indoor source of emissions, such as the Plant
      Collections property of the Department, the Air Conditioned System and the
      volatile compounds of the copying machine was responsible of high particle
      content. External factors such as weather conditions or human activities
      contributed exacerbating symptoms. As Conclusion, the knowledge of airborne
      biological particle content could be a useful tool in minimising allergy symptoms
      when environmental conditions render them inevitable.

PMID- 15736717
TI  - Prospective safety study of immunotherapy administered in a cluster schedule.
AB  - Cluster immunotherapy is becoming an alternative to conventional IT due to its
      shorter schedule, but the safety of such schedule is still controversial. At
      present, only few studies assess the risk of immunotherapy in a prospective
      manner, in well-controlled patients, using the same extract and intending to
      evaluate a single schedule. The aim of the present study is to evaluate the
      safety of a cluster immunotherapy administration regimen. A total of 91
      outpatients (41 male and 50 female), with a mean age of 25 years old (range: 16
      50) were included. Sixty-one patients were diagnosed mild to moderate asthma and
      30 rhinoconjunctivitis. Forty-six of the enrolled patients were sensitised to
      pollen (Lolium perenne and/or Olea europea), 38 to Dermatophagoides pteronyssinus
      and 7 to Alternaria alternata. Patients received specific immunotherapy following
      a five-week cluster schedule. It was considered as a preseasonal treatment, that
      is, it was accomplished before olive and grass initial pollinating months in this
      area (March--April). A total 1029 injections were administered during the
      induction phase. Adverse reactions were assessed and classified according to the
      EAACI criteria. The average number of visits to maximum dose was 6 (range 2-10),
      and 70 patients (77%) reached the maximum between 5-7 visits. In each of the
      visits an average of 2 (range 1-3) injections were administered. Eighty-one of
      the 91 initially enrolled patients (89%) completed the cluster schedule. The
      total number of reactions were 47 (24 local and 23 systemic). No fatal reactions
      were observed. Since the total number of administered injections was 1029, the
      relative frequency of adverse reactions was 4.6% (2.3% local and 2.2% systemic).
      The percentage of patients affected by systemic reaction was 18% and by local
      reaction 14%. No relationship can be shown between adverse reactions and gender
      or disease. However, a clear relationship with the composition of immunotherapy
      has been shown, with a lower risk of adverse reactions associated with the
      extract of D. pteronyssinus. The shorter period required to achieve the
      maintenance dose, with a similar frequency of adverse events, leads to the
      conclusion that the proposed administration regimen can be an alternative to
      conventional schedule to increase patient compliance.

PMID- 15736718
TI  - Antigen-presenting cells in the hypertrophic pharyngeal tonsils: a histochemical,
      immunuhistochemical and ultrastructural study.
AB  - The antigen presenting cells (APCs) with special interest to dendritic cells
      (DC), were investigated in 28 hypertrophic and 10 control pharyngeal tonsils of
      children by histochemistry, immunohistochemistry and electron microscopy. In this
      study, we are trying to clarify the function and classification of APC in
      pharyngeal tonsils using morphologic criteria, Human Leukocyte Antigen Monoclonal
      Antibody (HLA-DR MoAb), which is specific for APCs, and acid phosphatase (APh)
      reacting with both phagosomes and lysosomes. The surface epithelium of the
      patient group examined by light microscopy, heavy infiltration of lymphocytes,
      degenerated columnar cells and a few HLA-DR MoAb (+) columnar cells was observed.
      Additionally, a significant number of APCs which were Langerhans cells (LCs),
      interdigitating dendritic cell (IDC), follicular dendritic cell (FDC) and
      macrophages were stained with both HLA-DR MoAb and APh in the epithelial,
      interfollicular-subepithelial and follicular areas. Ultrastructural examinations
      revealed that lymphocytes, macrophages, LC and M cells were found among the
      surface columnar epithelial cells of the patient group. The interactions between
      M cells and LC suggested that M cells probably passed antigens from surface to
      LC. In the interfollicular-subepithelial areas of the hypertrophic pharyngeal
      tonsil, IDCs were in close contact with lymphocytes, macrophages and plasma
      cells. Seven types of FDCs (FDC-1 - FDC-7) were recognised according to their
      ultrastructural appearances. Differentiated FDCs (FDC-4) were also in close
      contact with each active subtype of FDCs in follicular areas besides lymphocytes.
      These findings supported the idea that although the pharyngeal tonsils contained
      several types of active APCs, only DC were in close contact with immunocompetent
      cells and the other APC's. Therefore, these morphologic appearances of DC could
      be a sign of function to initiate the immune response of the pharyngeal tonsil.

PMID- 15736719
TI  - The multiple faces of nonsteroidal antiinflammatory drug hypersensitivity.
AB  - Based on the clinical picture and triggering drugs, allergic and pseudoallergic
      adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) can be
      classified in four patterns : respiratory, cutaneous, mixed and systemic. This
      categorization is useful for the purpose of describing patient populations
      included in studies about NSAID adverse reactions as well as for the routine
      management of the patient in the clinical setting.

PMID- 15736720
TI  - IgE reactivity to profilin in Platanus acerifolia pollen-sensitized subjects with
      plant-derived food allergy.
AB  - BACKGROUND: The presence of profilin-specific IgE antibodies is a cause of cross
      reactivity between botanically-unrelated allergen sources. Recently, the
      association between Platanus acerifolia pollinosis and plant-derived food allergy
      has been described. The aim of this study was to ascertain whether the P.
      acerifolia profilin is involved in such cross-reactivity. METHODS: Twenty-three
      patients suffering from Platanus acerifolia pollinosis and plant-derived food
      allergy were evaluated in an allergy department. Specific IgE levels to P.
      acerifolia pollen, P. acerifolia profilin and food extracts were measured.
      Molecular masses of IgE-binding proteins were calculated by Western blotting and
      cross-reactivity studies among P. acerifolia profilin and different food extracts
      were evaluated by Enzyme AllergoSorbent Test (EAST)-inhibition assays. Also, EAST
      inhibition assays with the two known P. acerifolia allergens, Pla a 1 and Pla a
      2, were performed. RESULTS: Surprisingly, a high IgE-binding prevalence (90%) of
      P. acerifolia profilin was found. EAST-inhibition showed high inhibition values
      when Platanus acerifolia pollen extract was used as free phase and plant-derived
      food extracts as solid phase, whereas the other way round showed low inhibition
      values. IgE reactivity to profilin was studied using a pool of patient sera, by
      EAST-inhibition assays with hazelnut, apple peel, peanut, chickpea and peanut
      extracts as solid phase and no inhibition was obtained when P. acerifolia
      profilin was used as inhibitor phase. The same results were obtained when
      purified Pla a 1 and Pla a 2 were also used as inhibitor phase. CONCLUSIONS: The
      clinical association observed between Platanus acerifolia pollen and plant
      derived food could be explained by the in vitro IgE cross-reactivity detected by
      EAST-inhibition. However, it appears that neither P. acerifolia profilin nor the
      two major allergens described (Pla a 1 and Pla a 2) can explain such a strong
      cross-reactivity.

PMID- 15736721
TI  - Chronic autoreactive urticaria at six years of age.
AB  - A case of chronic urticaria in a child 6 years old is described. The strong skin
      reactivity upon intradermal injection of autologous serum suggested an
      autoreactive pathogenesis; however, patient's serum was unable to induce
      histamine release from basophils in-vitro, indicating the presence of a histamine
      releasing factor specific for mast cells, and possibly other than an anti
      FcepsilonRI or anti-IgE antibody. Intradermal test with autologous serum may be
      useful in revealing the autoreactive nature of chronic urticaria and can avoid a
      frustrating search for other causes of the disease. In children presenting with
      chronic or recurrent urticaria the diagnostic workup should include the
      autologous serum skin test.

PMID- 15736722
TI  - Bread eating induced oral angioedema due to alpha-amylase allergy.
AB  - Inhalation of dust from different enzymes can be the cause of occupational asthma
      in exposed workers. Enzymes from different sources are being increasingly used in
      food. Few cases of food allergy to alpha-amylase induced by eating bread have
      been reported. Those cases were reported in bakery-related patients and in a
      pharmaceutical-industry worker. A 25-year-old farmer suffered sneezing,
      rhinorrhea, oropharyngeal itching, hoarseness, cough, and non-wheezy dyspnea
      after eating white bread. Skin prick tests (SPT) with common aeroallergens and
      food allergens revealed only sensitization to Olea europaea pollen. SPT response
      was positive to Aspergillus oryzae alpha-amylase. Specific IgE against alpha
      amylase was positive. A double-blind placebo-controlled challenge with 5 mg of
      uncooked -amylase induced sneezing, cough, oral angioedema within 10 minutes. The
      provocation test with 50 g of white bread gave similar findings. This case
      indicates that alpha-amylase contained in bread may provoke IgE-mediated food
      allergy. It is worth noting that in this case, the only source of alpha-amylases
      sensitization was bread.

PMID- 15736723
TI  - Paradoxical coexistence of atopic asthma and Human T-Lymphotropic Virus Type I
      (HTLV-I) infection: a case report.
AB  - In this case report, the authors report the presence of two supposedly antagonic
      immune diseases in the same patient. The patient is a 45-year-old white woman
      with a history of asthma and allergic rhinitis for the last 10 years. Asthmatic
      symptoms were present and were triggered after exposure to dust and mold. Her
      Human T-Lymphotropic Virus Type I (HTLV-I) seropositive status was detected by
      chance five years ago during a routine screening for blood donation. Skin prick
      tests were positive for Dermatophagoides pteronyssinus, Dermatophagoides farinae
      and Blomia tropicalis. Cytokine levels in unstimulated cultures were: IFNgamma=
      1195 pg/ ml, TNFalpha = 460 pg/ml, IL5 = 41 pg/ml and IL10 = 265 pg/ml.

PMID- 15736724
TI  - The arts in health and healing: a personal journey.

PMID- 15736725
TI  - Living with diabetes: The holistic experiences of Nigerians and African
      Americans.
AB  - The purpose of this study was to understand the holistic and transcultural
      experience of living with, and growing old with, diabetes for Nigerians and for
      African Americans. In this study, 5 themes were identified and described;
      however, 2 drives-fear and living-were the main coping strategies that
      participants used to balance their life holistically. The results show that in
      the face of their fears, subjects from both cultures never gave up their hope for
      living. Rather, they often sought out and used holistic and complementary
      approaches while maintaining their spiritual faith and hope.

PMID- 15736726
TI  - The lived experience of fibromyalgia in African American women.
AB  - This study aimed to learn what it is like for African American women to live with
      fibromyalgia. Van Manen's phenomenological method of writing and rewriting guided
      the inquiry. The sample included 10 women, who were interviewed for 30 to 60
      minutes each. Two agreed to second interviews, for a total of 12 interviews for
      data analysis. Data analysis revealed the following themes: (a) managing the
      symptoms, (b) becoming a self-advocate, (c) medications camouflage the pain, (d)
      coming to grips with the illness means making changes, (e) being accused of
      "taking a free ride" angers them, (f) support comes from self and spiritual
      connections, and (g) a certain amount of secrecy makes it easier to live with the
      illness. Recommendations focus on using a holistic approach to help African
      American women achieve or maintain their integrity.

PMID- 15736727
TI  - The effects of mindfulness-based stress reduction on nurse stress and burnout,
      Part II: A quantitative and qualitative study.
AB  - This article is the second in a series reporting on research exploring the
      effects of Mindfulness-based Stress Reduction on nurses and describes the
      quantitative data. The third article describes qualitative data. Treatment group
      participants reduced scores on 2 of 3 subscales of the Maslach Burnout Inventory
      significantly more than wait-list controls; within-group comparisons for both
      groups pretreatment and posttreatment revealed similar findings. Changes were
      maintained as long as 3-month posttreatment. Implications of these findings are
      discussed.

PMID- 15736728
TI  - How CAM helps systemic lupus erythematosus.
AB  - The symptoms associated with systemic lupus erythematosus can vary in location
      and severity and often have life-altering effects. Because the disease is
      chronic, the use of traditional medical therapy may not bring about the maximum
      benefit in many cases. In light of this, many people diagnosed with lupus may
      turn to complementary and alternative medicine (CAM) therapies to help treat
      their disease. This article examines some of the common CAM methods used in
      addition to conventional medical treatment. Some points to consider include
      effectiveness, safety, cost, and ethical concerns associated with the use of CAM.
      The integration of these treatments into the medical regimen of those being
      treated for lupus is also considered.

PMID- 15736729
TI  - The experience of immobility due to trauma.
AB  - Through a series of 9 artistic etchings, the author's feelings of her experience
      with immobility due to trauma naturally fell into 3 groups of 3. These groupings
      represent the natural organization of human experience and all stories-the
      beginning, the middle, and the end. Here, the author and artist shares an account
      of her healing journey that revealed itself through artistic expression.

PMID- 15736730
TI  - Parish nursing: inclusive or exclusive?

PMID- 15736731
TI  - The management of fractures with bone loss.

PMID- 15736732
TI  - The use of outcome scores in surgery of the shoulder.

PMID- 15736733
TI  - The importance of leg length discrepancy after total hip arthroplasty.
AB  - We assessed leg length discrepancy and hip function in 90 patients undergoing
      primary total hip arthroplasty before surgery and at three and 12 months after.
      Function was measured using the Oxford hip score (OHS). After surgery the mean
      OHS improved by 26 points after three months and by 30 points after 12. After
      operation 56 (62%) limbs were long by a mean of 9 mm and this was perceived by 24
      (43%) patients after three months and by 18 (33%) after 12. The mean OHS in
      patients who perceived true lengthening was 27% worse than the rest of the
      population after three months and 18% worse after 12. In 55 (98%) patients,
      lengthening occurred in the femoral component. Appropriate placement of the
      femoral component could significantly reduce a patient's perception of
      discrepancy of length.

PMID- 15736734
TI  - Stability of the Birmingham hip resurfacing arthroplasty at two years. A
      radiostereophotogrammetric analysis study.
AB  - The Birmingham hip resurfacing metal-on-metal arthroplasty was introduced in 1997
      and has shown promising short- to mid-term results. We used
      radiostereophotogrammetric analysis (RSA) to study the stability of 20
      resurfacing arthroplasties over a follow-up period of 24 months. Radiological
      examinations for RSA were performed immediately after surgery and at two, six, 12
      and 24 months after operation. Precision and detection of migration thresholds
      (non-zero movement) were calculated. All the results corresponded well to those
      found in similar experimental arrangements with standard hip prostheses.
      Migration of the cup and vertical and mediolateral migration of the head were
      calculated. The values were low at two years compared with those of earlier
      studies of cemented femoral components in conventional total hip replacements
      indicating that there was no evidence of excessive early migration or loosening
      of the components.

PMID- 15736735
TI  - Comparison of offset in Birmingham hip resurfacing and hybrid total hip
      arthroplasty.
AB  - Hip resurfacing is being performed more frequently in the United Kingdom. The
      possible benefits include more accurate restoration of leg length, femoral offset
      and femoral anteversion than occurs after total hip arthroplasty (THA). We
      compared anteroposterior radiographs from 26 patients who had undergone hybrid
      THA (uncemented cup/cemented stem), with 28 who had undergone Birmingham Hip
      Resurfacing arthroplasty (BHR). We measured the femoral offset, femoral length,
      acetabular offset and acetabular height with reference to the normal
      contralateral hip. The data were analysed by paired t-tests. There was a
      significant reduction in femoral offset (p = 0.0004) and increase in length (p =
      0.001) in the BHR group. In the THA group, there was a significant reduction in
      acetabular offset (p = 0.0003), but femoral offset and overall hip length were
      restored accurately. We conclude that hip resurfacing does not restore hip
      mechanics as accurately as THA.

PMID- 15736736
TI  - Birmingham hip resurfacing arthroplasty. A minimum follow-up of five years.
AB  - We report the survival at five years of 144 consecutive metal-on-metal
      resurfacings of the hip implanted between August 1997 and May 1998. Failure was
      defined as revision of either the acetabular or femoral component for any reason
      during the study period. The survival at the end of five years was 98% overall
      and 99% for aseptic revisions only. The mean age of the patients at implantation
      was 52.1 years. Three femoral components failed during the first two years, two
      were infected and one fractured. A single stage revision was carried out in each
      case. No other revisions were performed or are impending. No patients were lost
      to follow-up. Four died from unrelated causes during the study period. This study
      confirms that hip resurfacing using a metal-on-metal bearing of known provenance
      can provide a solution in the medium term for the younger more active adult who
      requires surgical intervention for hip disease.

PMID- 15736737
TI  - Is there a role for extended antibiotic therapy in a two-stage revision of the
      infected knee arthroplasty?
AB  - All major studies have incorporated the use of prolonged courses of parenteral or
      oral antibiotic therapy in the management of two-stage revision of an infected
      total knee arthroplasty. We present a series of 59 consecutive patients, all with
      microbiologically-proven deep infection of a total knee arthroplasty, in whom a
      prolonged course of antibiotic therapy was not routinely used. The mean follow-up
      was 56.4 months (24 to 114). Of the 38 patients who underwent a staged exchange,
      infection was successfully eradicated in 34 (89%) but recurrent or persistent
      infection was present in four (11%). Our rate of cure for infection is similar to
      that reported elsewhere. We conclude that a prolonged course of antibiotic
      therapy seems not to alter the incidence of recurrent or persistent infection.
      The costs of the administration of antibiotics are high and such a regime may be
      unnecessary.

PMID- 15736738
TI  - Triple arthrodesis: is bone grafting necessary? The results in 100 consecutive
      cases.
AB  - Our aim was to evaluate the results of triple arthrodesis, performed without the
      use of supplementary bone graft. We carried out a retrospective review of 100
      consecutive triple arthrodeses. All the operations had been performed by the
      senior author (TSS) using a standard technique. Only local bone graft from the
      excised joint surfaces had been used, thereby avoiding complications at the donor
      site. The mean age of the patients at surgery was 58 years (18 to 84). The mean
      time to union was 5.1 months (3 to 17). There were 75 good, 20 fair and five poor
      results. There were four cases of nonunion. Our study has shown that comparable
      rates of union are achieved without the need for supplementary bone graft from
      the iliac crest or other donor site.

PMID- 15736739
TI  - Early results of autologous chondrocyte implantation in the talus.
AB  - Autologous chondrocyte implantation (ACI) has been used most commonly as a
      treatment for cartilage defects in the knee and there are few studies of its use
      in other joints. We describe ten patients with an osteochondral lesion of the
      talus who underwent ACI using cartilage taken from the knee and were
      prospectively reviewed with a mean follow-up of 23 months. In nine patients the
      satisfaction score was 'pleased' or 'extremely pleased', which was sustained at
      four years. The mean Mazur ankle score increased by 23 points at a mean follow-up
      of 23 months. The Lysholm knee score returned to the pre-operative level at one
      year in three patients, with the remaining seven showing a reduction of 15% at 12
      months, suggesting donor-site morbidity. Nine patients underwent arthroscopic
      examination at one year and all were shown to have filled defects and stable
      cartilage. Biopsies taken from graft sites showed mostly fibrocartilage with some
      hyaline cartilage. The short-term results of ACI for osteochondral lesions of the
      talus are good despite some morbidity at the donor site.

PMID- 15736740
TI  - Trapezius transfer in brachial plexus palsy. Correlation of the outcome with
      muscle power and operative technique.
AB  - Between March 1994 and June 2003, 80 patients with brachial plexus palsy
      underwent a trapezius transfer. There were 11 women and 69 men with a mean age of
      31 years (18 to 69). Before operation a full evaluation of muscle function in the
      affected arm was carried out. A completely flail arm was found in 37 patients
      (46%). Some peripheral function in the elbow and hand was seen in 43 (54%). No
      patient had full active movement of the elbow in combination with adequate
      function of the hand. Patients were followed up for a mean of 2.4 years (0.8 to
      8). We performed the operations according to Saha's technique, with a
      modification in the last 22 cases. We demonstrated a difference in the results
      according to the pre-operative status of the muscles and the operative technique.
      The transfer resulted in an increase of function in all patients and in 74 (95%)
      a decrease in multidirectional instability of the shoulder. The mean increase in
      active abduction was from 6 degrees (0 to 45) to 34 degrees (5 to 90) at the last
      review. The mean forward flexion increased from 12 degrees (0 to 85) to 30
      degrees (5 to 90). Abduction (41 degrees) and especially forward flexion (43
      degrees) were greater when some residual function of the pectoralis major
      remained (n = 32). The best results were achieved in those patients with most pre
      operative power of the biceps, coracobrachialis and triceps muscles (n = 7), with
      a mean of 42 degrees of abduction and 56 degrees of forward flexion. Active
      abduction (28 degrees) and forward flexion (19 degrees) were much less in
      completely flail shoulders (n = 34). Comparison of the 19 patients with the Saha
      technique and the 15 with the modified procedure, all with complete paralysis,
      showed the latter operation to be superior in improving shoulder stability. In
      all cases a decrease in instability was achieved and inferior subluxation was
      abolished. The results after trapezius transfer depend on the pre-operative
      pattern of paralysis and the operative technique. Better results can be achieved
      in patients who have some function of the biceps, coracobrachialis, pectoralis
      major and triceps muscles compared with those who have a complete palsy. A simple
      modification of the operation ensures a decrease in joint instability and an
      increase in function.

PMID- 15736741
TI  - Primary semi-constrained arthroplasty for chronic fracture-dislocations of the
      elbow.
AB  - We present six patients with chronic dislocation of the elbow who were treated by
      primary semiconstrained total elbow arthroplasty. All were women with a mean age
      of 65 years (51 to 76), the mean interval between dislocation and surgery was 17
      weeks (5 to 52) and the mean follow-up 58 months (24 to 123). The most dramatic
      improvement was in function. The mean American Shoulder and Elbow Surgeon score
      was 5.2 times better (p < 0.001) and the mean total range of movement increased
      from 33 degrees to 121 degrees (p < 0.001) after operation. Three patients
      developed wear of polyethylene. One required revision for a periprosthetic
      fracture, and another required a bushing exchange. Primary semiconstrained elbow
      arthroplasty provides significant, predictable functional improvement. Potential
      solutions for wear of polyethylene include a different operative technique or
      design of implant. Despite the high incidence of such wear, total elbow
      arthroplasty should be considered as a viable treatment option for chronic
      dislocation of the elbow in elderly patients.

PMID- 15736742
TI  - The effect of psychological disturbance on symptoms, self-reported disability and
      surgical outcome in carpal tunnel syndrome.
AB  - In a prospective study, we have evaluated the impact of psychological disturbance
      on symptoms, self-reported disability and the surgical outcome in a series of 110
      patients with carpal tunnel syndrome. Self-reported severity of symptoms and
      disability were assessed using the patient evaluation measure and the Boston
      carpal tunnel questionnaire. Psychological distress was assessed using the
      hospital anxiety and depression scale. There was a significant association
      between psychological disturbance and the pre-operative symptoms and disability.
      However, there was no significant association between pre-operative psychological
      disturbance and the outcome of surgery at six months. We concluded that patients
      with carpal tunnel syndrome should not be denied surgery because of pre-operative
      psychological disturbance since it does not adversely affect the surgical
      outcome.

PMID- 15736743
TI  - A computer touch-screen version of the North American Spine Society outcome
      assessment instrument for the lumbar spine.
AB  - We validated the North American Spine Society (NASS) outcome-assessment
      instrument for the lumbar spine in a computerised touch-screen format and
      assessed patients' acceptance, taking into account previous computer experience,
      age and gender. Fifty consecutive patients with symptomatic and radiologically
      proven degenerative disease of the lumbar spine completed both the hard copy
      (paper) and the computerised versions of the NASS questionnaire. Statistical
      analysis showed high agreement between the paper and the touch-screen computer
      format for both subscales (intraclass correlation coefficient 0.94, 95%
      confidence interval (0.90 to 0.97)) independent of computer experience, age and
      gender. In total, 55% of patients stated that the computer format was easier to
      use and 66% preferred it to the paper version (p < 0.0001 among subjects
      expressing a preference). Our data indicate that the touch-screen format is
      comparable to the paper form. It may improve follow-up in clinical practice and
      research by meeting patients' preferences and minimising administrative work.

PMID- 15736744
TI  - Sanders classification of fractures of the os calcis. An analysis of inter- and
      intra-observer variability.
AB  - Our study was undertaken to assess the inter- and intra-observer variability of
      the classification system of Sanders for calcaneal fractures. Five consultant
      orthopaedic surgeons with different subspecialty interests classified CT scans of
      28 calcaneal fractures using this classification system. After six months, they
      reclassified the scans. Kappa statistics were used to analyse the two groups. The
      interobserver variability of the classification system was 0.32 (95% confidence
      interval (CI) 0.26 to 0.38). The subclasses were then combined and assessment of
      agreement between the general classes as a whole gave a kappa value of 0.33 (95%
      CI 0.25 to 0.41). The mean kappa value for intra-observer variability of the
      classification system was 0.42 (95% CI 0.22 to 0.62). When the subclasses were
      combined, it was 0.45 (95% CI 0.21 to 0.65). Our results show that, despite its
      popularity, the classification system of Sanders has only fair agreement among
      users.

PMID- 15736745
TI  - Thromboprophylaxis in pelvic and acetabular trauma surgery. The role of early
      treatment with low-molecular-weight heparin.
AB  - We prospectively studied the outcome of a protocol of prophylaxis for deep vein
      thrombosis (DVT) in 103 consecutive patients undergoing surgical stabilisation of
      pelvic and acetabular fractures. Low-molecular-weight heparin (LMWH) was
      administered within 24 hours of injury or on achieving haemodynamic stability.
      Patients were screened for proximal DVT by duplex ultrasonography performed ten
      to 14 days after surgery. The incidence of proximal DVT was 10% and of pulmonary
      embolus 5%. Proximal DVT developed in two of 64 patients (3%) who had received
      LMWH within 24 hours of injury, but in eight of 36 patients (22%) who received
      LMWH more than 24 hours after the injury (p < 0.01). We conclude that LMWH, when
      begun without delay, is a safe and effective method of thromboprophylaxis in high
      risk patients with major pelvic or acetabular fractures.

PMID- 15736746
TI  - The effect of iron supplementation on the level of haemoglobin after lower limb
      arthroplasty.
AB  - We randomised 120 patients who were undergoing either primary total hip or knee
      arthroplasty to receive either ferrous sulphate or a placebo for three weeks
      after surgery. The level of haemoglobin and absolute reticulocyte count were
      measured at one and five days, and three and six weeks after operation. Ninety
      nine patients (ferrous sulphate 50, placebo 49) completed the study. The two
      groups differed only in the treatment administered. Recovery of level of
      haemoglobin was similar at five days and three weeks and returned to 85% of the
      pre-operative level, irrespective of the treatment group. A small, albeit greater
      recovery in the level of haemoglobin was identified at six weeks in the ferrous
      sulphate group in both men (ferrous sulphate 5%, placebo 1.5%) and women (ferrous
      sulphate 6%, placebo 3%). The clinical significance of this is questionable and
      may be outweighed by the high incidence of reported side effects of oral iron and
      the cost of the medication. Administration of iron supplements after elective
      total hip or total knee arthroplasty does not appear to be worthwhile.

PMID- 15736747
TI  - Reconstruction using an autograft containing tumour treated by liquid nitrogen.
AB  - We describe a method of reconstruction using tumour-bearing autograft treated by
      liquid nitrogen in 28 patients. The operative technique consisted of en bloc
      excision of the tumour, removal of soft tissue, curettage of the tumour, drilling
      and preparation for internal fixation or prosthetic replacement before incubation
      for 20 minutes in liquid nitrogen, thawing at room temperature for 15 minutes,
      thawing in distilled water for ten minutes, and internal fixation with an
      intramedullary nail, plate or composite use of prosthetic replacement. Bone graft
      or cement was used to augment bone strength when necessary. The limb function was
      rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three
      (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at
      a mean of 19.8 months after the operation, while 21 remained free from disease
      with a mean follow-up of 28.1 months (10 to 54). One patient is alive with
      disease. Bony union was seen at a mean of 6.7 months after the operation in 26
      patients. Complications were encountered in seven patients, including three deep
      infections, two fractures, and two local recurrences. All were managed
      successfully. Our results suggest that this is a simple and effective method of
      biological reconstruction.

PMID- 15736748
TI  - Pathomorphology and treatment of congenital anterolateral bowing of the tibia
      associated with duplication of the hallux.
AB  - Congenital unilateral anterolateral tibial bowing in combination with a bifid
      ipsilateral great toe is a very rare deformity which resembles the anterolateral
      tibial bowing that occurs in association with congenital pseudarthrosis of the
      tibia. However, spontaneous resolution of the deformity without operative
      treatment and with a continuously straight fibula has been described in all
      previously reported cases. We report three additional cases and discuss the
      options for treatment. We suggest that this is a specific entity within the field
      of anterolateral bowing of the tibia and conclude that it has a much better
      prognosis than congenital pseudarthrosis of the tibia, although conservative
      treatment alone may not be sufficient.

PMID- 15736749
TI  - Brachial plexus palsy secondary to birth injuries.
AB  - We describe the long-term results in ten patients with obstetric brachial plexus
      palsy of anterior shoulder release combined with transfer of teres major and
      latissimus dorsi posteriorly and laterally to allow them to act as external
      rotators. Eight patients had a lesion of the superior trunk and two some
      involvement of the entire brachial plexus. The mean age at operation was six
      years, and the mean follow-up was 30 years. Before operation, the patients were
      unable actively to rotate the arm externally beyond neutral, although this
      movement was passively normal. All showed decreased strength of the external
      rotator, but had normal strength of the internal rotator muscles. Radiologically,
      no severe bony changes were seen in the glenohumeral joint. No clinically
      detectable improvement of active abduction was noted in any patient. The mean
      active external rotation after operation was 36.5 degrees. This was maintained
      for a mean of ten years, and then deteriorated in eight patients. At the latest
      follow-up the mean active external rotation was 10.5 degrees. The early
      satisfactory results of the procedure were not maintained. In the long term there
      was loss of active external rotation, possibly because of gradual degeneration of
      the transferred muscles, contracture of the surrounding soft tissues and
      degenerative changes in the glenohumeral joint.

PMID- 15736750
TI  - Late orthopaedic sequelae following meningococcal septicaemia. A multicentre
      study.
AB  - Between 1990 and 2001, 24 children aged between 15 months and 11 years presented
      with late orthopaedic sequelae after meningococcal septicaemia. The median time
      to presentation was 32 months (12 to 119) after the acute phase of the disease.
      The reasons for referral included angular deformity, limb-length discrepancy,
      joint contracture and problems with prosthetic fitting. Angular deformity with or
      without limb-length discrepancy was the most common presentation. Partial growth
      arrest was the cause of the angular deformity. Multiple growth-plate involvement
      occurred in 14 children. The lower limbs were affected much more often than the
      upper. Twenty-three children underwent operations for realignment of the
      mechanical axis and limb-length equalisation. In 15 patients with angular
      deformity around the knee the deformity recurred. As a result we recommend
      performing a realignment procedure with epiphysiodesis of the remaining growth
      plate when correcting angular deformities.

PMID- 15736751
TI  - The Oxford hip and knee outcome questionnaires for arthroplasty.
AB  - The Oxford hip and knee scores are used to measure the outcome after primary
      total hip and knee replacement. We propose a new layout for the instrument in
      which patients are always asked about both limbs. In addition, we have defined an
      alternative scoring method which accounts for missing data. Over a period of 4.5
      years, 4086 (1423 patients) and 5708 (1458 patients) questionnaires were
      completed for hips and knees, respectively. The hip score had a pre-operative
      median of 70.8 (interquartile range (IQR) 58.3 to 81.2) decreasing to 20.8 (IQR
      10.4 to 35.4) after one year. The knee score had a pre-operative median of 68.8
      (IQR 56.2 to 79.2) decreasing to 29.2 (IQR 14.6 to 45.8). There was no further
      significant change in either score after one year. As a result of the data
      analysis, we suggest that the score percentiles can be used as a standard for
      auditing patients before and after operation.

PMID- 15736752
TI  - Treatment of infected retained implants.
AB  - We have prospectively studied the outcome of infections associated with implants
      which were retained and treated using a standardised antimicrobial protocol. Over
      a period of four years, we studied 24 consecutive patients who had symptoms of
      infection for less than one year, a stable implant, no sinus tract and a known
      pathogen which was susceptible to recommended antimicrobial agents. The
      infections involved hip prostheses (14), knee prostheses (5), an internal
      fixation device (4), and an ankle prosthesis (1). Twenty patients had a
      successful outcome at a median follow-up of 3.7 years (1.8 to 4.7); four had
      failure of the implant after a median follow-up of 1.2 years (0.3 to 2.5). The
      probability of survival without failure of treatment was 96% at one year (95%
      confidence interval (CI) 88 to 100), 92% at two years (95% CI 80 to 100) and 86%
      at three years (95% CI 72 to 100). Patients with a short-term infection but with
      a stable implant, no sinus tract and a known pathogen may be successfully treated
      by retention of the implant and the use of a standardised regimen of
      antimicrobial treatment.

PMID- 15736753
TI  - Cervical myelopathy caused by an exostosis of the posterior arch of C1.
AB  - We report a case of vertebral osteochondroma of C1 causing cord compression and
      myelopathy in a patient with hereditary multiple exostosis. We highlight the
      importance of early diagnosis and the appropriate surgery in order to obtain a
      satisfactory outcome.

PMID- 15736754
TI  - Exercise-induced strain and strain rate in the distal radius.
AB  - Strains applied to bone can stimulate its development and adaptation. High
      strains and rates of strain are thought to be osteogenic, but the specific dose
      response relationship is not known. In vivo human strain measurements have been
      performed in the tibia to try to identify optimal bone strengthening exercises
      for this bone, but no measurements have been performed in the distal radial
      metaphysis, the most frequent site of osteoporotic fractures. Using a strain
      gauged bone staple, in vivo dorsal metaphyseal radial strains and rates of strain
      were measured in ten female patients during activities of daily living, standard
      exercises and falls on extended hands. Push-ups and falling resulted in the
      largest compression strains (median 1345 to 3146 microepsilon, equivalent to a
      0.1345% to 0.3146% length change) and falling exercises in the largest strain
      rates (18582 to 45954 microepsilon/s). On the basis of their high strain and/or
      strain rates these or variations of these exercises may be appropriate for distal
      radial metaphyseal bone strengthening.

PMID- 15736755
TI  - Tricalcium-phosphate and hydroxyapatite bone-graft extender for use in impaction
      grafting revision surgery. An in vitro study on human femora.
AB  - Impacted morsellised allografts have been used successfully to address the
      problem of poor bone stock in revision surgery. However, there are concerns about
      the transmission of pathogens, the high cost and the shortage of supply of donor
      bone. Bone-graft extenders, such as tricalcium phosphate (TCP) and hydroxyapatite
      (HA), have been developed to minimise the use of donor bone. In a human cadaver
      model we have evaluated the surgical and mechanical feasibility of a TCP/HA bone
      graft extender during impaction grafting revision surgery. A TCP/HA allograft mix
      increased the risk of producing a fissure in the femur during the impaction
      procedure, but provided a higher initial mechanical stability when compared with
      bone graft alone. The implications of the use of this type of graft extender in
      impaction grafting revision surgery are discussed.

PMID- 15736756
TI  - Bacterial survival in the interfacial gap in gentamicin-loaded acrylic bone
      cements.
AB  - Clinical experience indicates the beneficial effects of antibiotic-loaded bone
      cement. Although in vitro studies have shown the formation of a biofilm on its
      surface they have not considered the gap between the cement and the bone. We have
      investigated bacterial survival in that gap. Samples with gaps 200 microm wide
      were made of different bone cements. These were stored dry ('pre-elution') or
      submersed in phosphate-buffered saline to simulate the initial release of
      gentamicin ('post-elution'). The gaps were subsequently inoculated with bacteria,
      which had been isolated from infected orthopaedic prostheses and assessed for
      their sensitivity to gentamicin. Bacterial survival was measured 24 hours after
      inoculation. All the strains survived in plain cements. In the pre-elution
      gentamicin-loaded cements only the most gentamicin-resistant strain, CN5115,
      survived, but in post-elution samples more strains did so, depending on the
      cement tested. Although high concentrations of gentamicin were demonstrated in
      the gaps only the gentamicin-sensitive strains were killed. This could explain
      the increased prevalence of gentamicin-resistant infections which are seen
      clinically.

PMID- 15736757
TI  - The prognosis following acute primary glenohumeral dislocation.

PMID- 15736758
TI  - Intra-operative findings in varus osteoarthritis of the knee.

PMID- 15736760
TI  - An RN is offended by the misuse of nursing uniforms.

PMID- 15736759
TI  - Resurfacing arthroplasty of the hip.

PMID- 15736761
TI  - Whole-body scans can save lives in the war against cancer.

PMID- 15736762
TI  - A flu vaccine shortage can be devastating for LTC residents.

PMID- 15736763
TI  - RNs agree: secret shopper programs are worrisome.

PMID- 15736765
TI  - Should nurses go back to wearing white?

PMID- 15736764
TI  - RNs agree: secret shopper programs are worrisome.

PMID- 15736766
TI  - Placing an oropharyngeal airway.

PMID- 15736767
TI  - Do-not-use abbreviations: are you in compliance?

PMID- 15736768
TI  - Unstable angina: is your care up to snuff?

PMID- 15736769
TI  - Are you endangering your patients?

PMID- 15736770
TI  - Whooping cough makes its return.

PMID- 15736771
TI  - New hope for stroke patients.

PMID- 15736772
TI  - End horizontal violence.

PMID- 15736773
TI  - Risk-benefit analysis of the radiographic standards of care.

PMID- 15736774
TI  - Porcelain laminate veneers: 6- to 12-year clinical evaluation--a retrospective
      study.
AB  - The purpose of this study was to retrospectively evaluate the clinical
      performance of laminate veneers placed in the anterior segments of the dental
      arches over a 12-year period at two different private dental practices. Forty-six
      patients were restored with 182 porcelain laminate veneers. The veneers were
      studied for a mean observation time of 5.69 years. Color match, porcelain
      surface, marginal discoloration, and marginal integrity were clinically examined
      following modified CDA/Ryge criteria. On the basis of the criteria used, most of
      the veneers rated A. Risk of fracture was determined with a Kaplan-Meier survival
      analysis. Probability of survival of the 182 veneers was 94.4% at 12 years, with
      a low clinical failure rate (approximately 5.6%). Porcelain veneers must be
      bonded with a correct adhesive technique to reach this successful survival rate.

PMID- 15736775
TI  - Reduction of autogenous bone graft resorption by means of bio-oss coverage: a
      prospective study.
AB  - Bone grafting may be required prior to implant placement, at the time of implant
      placement, or subsequent to it. The aim of this study was to compare the healing
      of onlay block grafts when deproteinized bovine bone coverage was used with the
      healing of the grafts without such coverage. The purpose was a clinical
      evaluation of deproteinized bovine bone's ability to reduce grafted bone
      resorption. The results indicated that bovine bone can be placed over grafted
      areas, taking advantage of its osteoconductive properties and compensating for
      the natural bone resorption caused by remodeling.

PMID- 15736776
TI  - Treatment of completely edentulous patients with fixed implant-supported
      restorations: three consecutive cases of simultaneous immediate loading in both
      maxilla and mandible.
AB  - This article aims to: (1) describe the treatment of three consecutive completely
      edentulous patients with fixed implant-supported restorations, including
      simultaneous same-day immediate loading with fixed provisional restorations in
      both jaws; and (2) illustrate a step-by-step definitive restoration approach. All
      patients followed the same diagnostic protocol. One surgical intervention was
      performed for simultaneous implant placement in both maxilla and mandible.
      Following implant placement, all patients received a simultaneous, same-day,
      complete-arch, screw-retained provisional restoration in both jaws according to
      the "pickup" technique. After healing, final impressions were taken, and
      occlusion recorder devices were prepared on working casts. For the first occlusal
      record, the "half-provisionals" method was used. Definitive solid abutments were
      used for both laboratory and clinical procedures. After casting and finishing,
      the frameworks were tried in, and a new occlusal record was made. The definitive
      segmented restorations consisted of four fixed partial dentures in the maxilla
      and three in the mandible and were cemented with provisional cement. All patients
      received a nightguard. The pickup technique facilitated simultaneous immediate
      loading in both maxilla and mandible. A complete, fixed, segmented rehabilitation
      supported by six to eight anteroposterior implants is a reproducible treatment
      for completely edentulous patients when optimal anatomic conditions are present.

PMID- 15736777
TI  - Clinical and histologic evaluation of the periodontal response to restorative
      procedures in the dog.
AB  - This study evaluated, in the dog, the periodontal response to resin-modified
      glass-ionomer cement or amalgam restorations placed in surgical windows and left
      for 124 days. Plaque control was performed in half of the sites. Histologic
      analyses showed that sites restored with amalgam were consistently more inflamed
      than sites restored with resin-modified glass-ionomer. Plaque control was
      associated with less inflammation in both cases. Some sites restored with resin
      modified glass-ionomer presented bone repair and a connective tissue lining. The
      inflammatory response of the periodontium to resin-modified glass-ionomer
      restorations is less pronounced than that associated with amalgam restorations.

PMID- 15736778
TI  - A reentry study on the use of bovine porous bone mineral, GTR, and platelet-rich
      plasma in the regenerative treatment of intrabony defects in humans.
AB  - This study compared the clinical effectiveness of a combination therapy
      consisting of bovine porous bone mineral (BPBM), guided tissue regeneration
      (GTR), and platelet-rich plasma (PRP) in the regeneration of periodontal
      intrabony defects in humans. Twenty-eight paired intrabony defects were
      surgically treated using a split-mouth design. Defects were treated with BPBM,
      GTR, and PRP (experimental), or with open-flap debridement (control). Clinical
      parameters evaluated included changes in attachment level, pocket depth, and
      defect fill as revealed by reentry at 6 months. Preoperative pocket depths,
      attachment levels, and transoperative bone measurements were similar for the two
      groups. Postsurgical measurements taken at 6 months revealed that both treatment
      modalities significantly decreased pocket depth and increased clinical attachment
      and defect fill compared to baseline. The differences between the experimental
      and control groups were 2.22+/-0.39 mm on buccal and 2.12+/-0.34 mm on lingual
      sites for pocket depth, 3.05+/-0.51 mm on buccal and 2.88+/-0.46 mm on lingual
      sites for gain in clinical attachment, and 3.46+/-0.96 mm on buccal and 3.42+/
      0.02 mm on lingual sites for defect fill. These differences between groups were
      statistically significant in favor of the experimental defects. The combined
      therapy was also clinically more effective than open-flap debridement. The
      superiority of the experimental group could not be attributed solely to the
      surgical intervention and was likely a result of the BPBM/GTR/ PRP application.
      Combining BPBM, GTR, and PRP was an effective modality of regenerative treatment
      for intrabony defects in patients with advanced periodontitis.

PMID- 15736779
TI  - Histomorphometric comparison of three bioabsorbable GTR barrier membranes in the
      canine model.
AB  - Guided tissue regeneration (GTR) using bioabsorbable barrier membranes has shown
      promising and somewhat predictable clinical results. However, limited information
      is available on the stages of histologic healing when these types of barriers are
      used. Therefore, the aim of this study was to compare three currently available
      bioabsorbable GTR barriers (type 1 collagen, polylactide/polyglycolide copolymer,
      and citric acid copolymer) for the treatment of surgically created periodontal
      dehiscences in dogs. Eight three-walled periodontal dehiscences were surgically
      created in the mandibles of six beagle dogs (four on each side of the jaw). The
      periodontal dehiscences were randomly assigned to receive one of the three
      barriers. One defect was left untreated to serve as a control. Histomorphometric
      analyses were conducted at 4 and 12 weeks. Data were analyzed using the Student
      Fisher test. The membrane-treated group had a statistically significant increase
      in new bone formation and connective tissue attachment compared to the nontreated
      control sites. However, no statistical difference was noted among the various
      membranes. In addition, no difference was found between test and control sites
      when new cementum was examined. Sites treated with barrier membranes achieved
      greater bone regeneration than nontreated control sites in the canine model.

PMID- 15736780
TI  - Microleakage of endodontically treated teeth restored with prefabricated posts
      and tooth-colored restorative materials.
AB  - This study evaluated the microleakage of endodontically treated teeth restored
      with prefabricated dowels and tooth-colored restoratives (Solitaire, Surefil,
      Filtek P60, Admira, Z-100) as core materials with and without the use of a
      flowable composite liner. A total of 200 extracted premolars were endodontically
      treated and prepared for post-core restorations. Prefabricated posts were
      inserted and cemented with resin cement into the root canals. Each resin system
      included the corresponding bonding agent for each respective flowable composite.
      For each group, half of the teeth were restored with composite alone, while the
      others were restored with the composite lined with flowable liner. Teeth were
      thermocycled for 1,000 cycles between 5 and 55 degrees C using a 30-second dwell
      time. The teeth were then coated with nail polish, placed in 5% methylene blue
      for 24 hours, sectioned, and scored for microleakage. Flowable liners reduced
      microleakage. Z-100 both with and without flowable liner demonstrated better
      resistance to leakage. Solitaire, Admira, and Filtek P60 showed more leakage than
      the other materials.

PMID- 15736781
TI  - Three-dimensional treatment planning for prosthetic rehabilitation.
AB  - All prosthetic rehabilitations require healthy, stable oral conditions. The
      biologic response to the preliminary treatment provides important criteria for
      planning the final reconstruction and permits testing of the desired prosthetic
      treatment goals within the unique patient-specific biologic conditions before
      final restoration. This study used long-term provisional restorations that
      corresponded in both form and function to the anticipated restorations. Intraoral
      testing of the diagnostic waxup is an outstanding basis for discussing the
      provisional as well as final restoration. As required, changes necessary to teeth
      form and position can be simply accomplished.

PMID- 15736782
TI  - The Cresco Bridge and implant concept: presentation of a technology for
      fabrication of abutment-free, passively fitting superstructures.
AB  - This article describes a new and cost-effective concept comprising innovative and
      simplified clinical and laboratory procedures for the rational fabrication of
      abutment-free, cast-titanium superstructures with passive fit to implants. Other
      alloys, such as precious metal or cobalt-chromium, can also be used. The
      precision of fit between the implants and superstructure is obtained by the
      Cresco Ti Precision method. This method is a user-friendly technology and can be
      adapted to most implant systems on the market. The method does not include any
      abutments, even when implants are positioned in extremely different angulations
      or inclined in a facial or palatal direction. Coupled with a simple All Parts
      Included (API) delivery system, the concept therefore represents an efficient
      treatment alternative.

PMID- 15736783
TI  - Short on progress. Joint Commission jumps into medical liability debate.

PMID- 15736784
TI  - Take the money and run. Bon Secours Health System tries to cut its losses by
      clearing out of the Garden State altogether.
AB  - In 2000, Bon Secours Health System began a growth spurt that added eight
      hospitals, spreading its operations across nine states. But now it's a different
      story; since last November the system has announced plans or deals to sell
      facilities in Florida and Virginia, and leave New Jersey entirely. Incoming CEO
      Richard Statuto, left, faces a handful of challenges. "We need to determine how
      effective they've been at right-sizing their organization," a Standard & Poor's
      analyst says.

PMID- 15736785
TI  - Competitive duel. FTC lawyer says Evanston deal caused 'sea change'.

PMID- 15736786
TI  - Balancing act. Bush budget reveals healthcare funding priorities.

PMID- 15736787
TI  - Dis-integration. Intermountain may sell HMO to avoid backlash.

PMID- 15736788
TI  - Changing venues. Scruggs billing lawsuit moves to state courts.

PMID- 15736789
TI  - Diversifying healthcare. Bridging the gap of care, treatment for minorities.

PMID- 15736790
TI  - Prescription for reducing paperwork. Medicare electronic prescriptions could be a
      step closer to reality.

PMID- 15736791
TI  - LifePoint battles Carilion.

PMID- 15736792
TI  - Residents not exempt from FICA.

PMID- 15736794
TI  - Putting a price on care. California coalition may expel high-cost providers from
      plan.

PMID- 15736793
TI  - Labor's success. Unions make strides recruiting healthcare workers.

PMID- 15736795
TI  - Holding out hope. CMS study to review payments to LTAC facilities.

PMID- 15736796
TI  - Getting the whole story. Don't assume that all published research is objective.

PMID- 15736797
TI  - No more procrastinating. Industry must eschew excuses and move fast on electronic
      health records.

PMID- 15736798
TI  - Quality in an academic setting. Cincinnati Children's teams execs, physicians,
      families to improve care systems.

PMID- 15736799
TI  - This time they really mean it. Annual survey shows healthcare organizations are
      committing more money to IT and installing EMRs is now their top priority.

PMID- 15736800
TI  - Plugged in. Memorial healthcare readies wireless hospital.

PMID- 15736802
TI  - Tailoring a device. Building grafts is a hands-on, labor-intensive process.

PMID- 15736801
TI  - Stealth fighter. Abdominal aortic aneurysms can kill quickly and silently. Some
      say the best prevention is increased screening and surgery to implant
      sophisticated grafts.

PMID- 15736803
TI  - Training surgeons.

PMID- 15736804
TI  - Opening sterile packets.

PMID- 15736805
TI  - Deep venous incompetence (DVI).

PMID- 15736806
TI  - An in-house course for first assistants (advanced scrub practitioners) in
      theatres.
AB  - It has become commonplace to see theatre practitioners undertaking the role of
      the first assistant to the surgeon in the absence of medical staff in the
      operating room (Martin 2004). At Kettering General Hospital we have devised,
      implemented and are in the process of evaluating a first assistant training
      package to facilitate a solution to the increasing problems arising from the
      challenges of the European Working Time Directive.

PMID- 15736807
TI  - The AfC reality.
AB  - The Agenda for Change (AfC) proposals were implemented in the workplace with
      effect from 1 December 2004. AfC is the new pay and conditions package applicable
      to every NHS organisation in all four countries of the UK.

PMID- 15736808
TI  - The duty of care: an update. Current legal principles.
AB  - The author had a twofold purpose in writing this article: firstly to inform
      readers of the current legal principles that inform the duty of care, and
      secondly to discuss these principles with reference to two recent cases.
      Practitioners giving consideration to these issues will be assisted in their
      professional decision-making processes.

PMID- 15736809
TI  - Childhood obesity.
AB  - There has been much public debate over the increasing global problem of obesity.
      The rise in obesity is not just confined to the adult population, childhood
      obesity is also on the increase. This article will highlight some of the issues
      contributing to the recent rise in childhood obesity and its associated health
      consequences. As healthcare professionals it is essential that we identify how
      the health-related factors of childhood obesity impact upon the care given in the
      perioperative environment.

PMID- 15736810
TI  - Angiostrongylosis--a recommendation, a reminder and a word of caution.

PMID- 15736811
TI  - Assessment of cytological criteria for diagnosing osteosarcoma in dogs.
AB  - OBJECTIVES: To evaluate the specific cytological criteria of osteosarcomas in
      dogs. METHODS: Significant cytological characteristics of osteosarcoma and benign
      mesenchymal bone proliferations were determined from imprint smears of 25 dogs
      with osteosarcoma (group 1) and 20 dogs admitted for removal of surgical bone
      implants after uncomplicated healing of bone fractures (group 2). RESULTS: Mild
      to moderate cellular necrosis occurred frequently in patients with osteosarcoma.
      The cytoplasm of osteoblasts was pale blue to blue with a more pronounced
      basophilia in group 2. In 48 per cent of the patients in group 1, but none in
      group 2, osteoblasts showed a slight to moderate eosinophilic cytoplasmic
      granulation. In both groups, osteoblasts contained one red to pale blue nucleus
      with one or two grey-red to blue nucleoli in group 2. Forty-four per cent of
      animals in group 1 had osteoblasts with more than two nucleoli per nucleus. The
      median nuclear:cytoplasmic ratio was higher in group 1 (1:2.0) than in group 2
      (1:3.5). Osteoblasts in group I were frequently seen to have a clumped chromatin
      pattern and showed significantly more criteria of malignancy (median six criteria
      per patient) than those in group 2 (median two criteria per patient). In group 1,
      mitoses of osteoblasts were detectable in 23 of 25 dogs, whereas only one dog in
      group 2 had evidence of mitotic osteoblasts. CLINICAL SIGNIFICANCE: Cytological
      criteria can be helpful in the diagnosis of canine osteosarcoma.

PMID- 15736812
TI  - Inheritance of dermoid sinus in the Rhodesian ridgeback.
AB  - OBJECTIVES: TO define the mode of inheritance of dermoid sinus. METHODS: A chi
      squared analysis was performed on data from 46 litters produced between 1990 and
      2001. Data were corrected to avoid bias in the segregation ratio. RESULTS: In
      data from 57 litters (n=492), 82 dermoid sinus positive offspring were observed.
      The frequency of affected offspring in the Swedish Rhodesian ridgeback population
      is estimated to be between 8 and 10 per cent. CLINICAL SIGNIFICANCE: Bias in
      heredity pattern may be caused by undetected dermoid sinus type V. Improved
      clinical diagnosis of all dermoid sinus types is therefore crucial.

PMID- 15736813
TI  - Cerebral and conjunctival haemorrhages associated with von Willebrand factor
      deficiency and canine angiostrongylosis.
AB  - A case of angiostrongylosis is described in a 14-month-old golden retriever
      bitch. Conjunctival haemorrhage and neurological signs, referable to a space
      occupying cerebral lesion, were associated with defective primary haemostasis
      caused by low levels of von Willebrand factor. Full clinical recovery followed
      treatment with desmopressin, fresh whole blood transfusion, fenbendazole and
      supportive care. The magnetic resonance image of the suspected organising
      haematoma is described. Similarities to the human condition, acquired von
      Willebrand syndrome, and a possible role for aberrant larval migration in
      haematoma formation are suggested.

PMID- 15736814
TI  - Hypercalcaemia associated with angiostrongylus vasorum in three dogs.
AB  - Hypercalcaemia was identified in three dogs that presented primarily for
      evaluation of respiratory disease. Angiostrongylosis was diagnosed in all three
      cases and both the respiratory signs and the hypercalcaemia resolved with
      treatment. Infection with Angiostrongylus vasorum is known to lead to formation
      of pulmonary granulomata. Granulomatous disease in humans may lead to
      hypercalcaemia secondary to increased unregulated production of 1,25
      dihydroxycholecalciferol by activated macrophages in the granulomata. In one of
      the three dogs, 1,25-dihydroxycholecalciferol was measured and found to be
      increased, providing supportive evidence for a similar mechanism in dogs. To the
      authors' knowledge, hypercalcaemia has not previously been reported in
      association with angiostrongylosis in dogs. Since prolonged untreated
      hypercalcaemia may lead to permanent impairment of renal function, dogs with
      angiostrongylosis should be evaluated for the presence of hypercalcaemia.

PMID- 15736815
TI  - Neosporosis in a young dog presenting with dermatitis and neuromuscular signs.
AB  - A 16-week-old, male boxer dog developed multifocal nodular dermatitis followed by
      rapidly progressive and fatal neuromuscular disease. Protozoal tachyzoites were
      demonstrated by aspiration and biopsy of dermal lesions. Necropsy and histology
      revealed necrotising inflammation associated with intralesional protozoal
      organisms in various organs including the brain, heart, skeletal muscle and skin.
      Serology suggested active infection with Neospora caninum. Immunohistochemistry
      provided a definitive diagnosis. Dermatitis is a finding rarely associated with
      juvenile neosporosis. The possible role of immunosuppression is discussed.

PMID- 15736816
TI  - Ethmoidal encephalocoele associated with seizures in a puppy.
AB  - A six-month-old puppy was presented for investigation of a seizure disorder.
      Neurological examination indicated persistent cerebral dysfunction in the absence
      of any identifiable metabolic disorder and magnetic resonance imaging revealed
      extension of the rostral lobes of the cerebrum into the nasal cavity. Despite
      symptomatic treatment, the puppy continued to exhibit seizures and appeared
      distressed and so was euthanased. Postmortem examination confirmed the abnormal
      anatomy of the rostral part of the brain and absence of a cribriform plate. There
      was extensive grey and white matter degeneration plus intraparenchymal
      haemorrhage in the abnormal brain tissue. The findings are consistent with a
      diagnosis of ethmoldal encephalocoele--a condition that has not previously been
      reported in the dog.

PMID- 15736817
TI  - Intracranial haemorrhage associated with Angiostrongylus vasorum infection in
      three dogs.
AB  - This report describes three dogs with intracranial haemorrhage secondary to
      severe coagulation defects associated with Angiostrongylus vasorum infection. The
      initial case was diagnosed at necropsy, with two subsequent cases diagnosed
      antemortem and successfully treated. The dogs ranged in age from 14 months to
      four years and were presented for evaluation of a severe, subacute onset of
      suspected cerebral disease. Magnetic resonance imaging performed on all three
      dogs was suggestive of multiple areas of intraparenchymal brain haemorrhage.
      Coagulation assays showed a consumptive coagulopathy resembling chronic
      disseminated intravascular coagulation. Postmortem examination of the initial
      case confirmed the presence of multiple intracranial and extracranial
      haemorrhages. An unexpected finding was that of a marked multifocal nematode
      infection of the lungs with an associated vasculopathy. The parasites were
      confirmed to be A vasorum. In the two other dogs, faecal examination by Baermann
      technique confirmed A vasorum infection. Both dogs were treated with fenbendazole
      and one was additionally given a plasma transfusion. Repeated coagulation assays
      were normal within one week. Neurological examinations were normal for both dogs
      within six weeks. This case series indicates that A vasorum infection should be
      considered as a possible aetiology of intracranial haemorrhage in dogs.

PMID- 15736818
TI  - What is your diagnosis? Posterior lens capsule disruption.

PMID- 15736819
TI  - English/German veterinary exchange programme.

PMID- 15736820
TI  - Mental disorders and drug abuse in persons living with HIV/AIDS.
AB  - This article reviews the literature on the prevalence of mental and substance use
      disorders among persons living with HIV/AIDS. Drug use, both injection and non
      injection, substantially increases the risk for HIV infection. While injection
      drug users have the highest prevalence rates for HIV, substantially elevated
      rates of HIV infection are also present among crack cocaine users and individuals
      with substance use disorders generally. Persons with HIV/AIDS and a mental and/or
      substance use disorder have highly variable patterns of accessing services.
      Persons with HIV/AIDS who have a serious mental illness are more highly involved
      with services than other groups. Most individuals with co-occurring disorders
      report some involvement with outpatient primary medical care, although ancillary
      services such as mental health and substance abuse treatment, transportation
      assistance, and case management improve involvement in medical care. Women with
      HIV/AIDS and co-occurring mental and substance use disorders experience unique
      vulnerabilities, particularly those related to exposure to traumatic events.
      Given the complexity of needs with which triply or multiply diagnosed individuals
      present, effective treatment programmes are likely to be those that provide some
      degree of integrated care.

PMID- 15736821
TI  - Literature on integrated HIV care: a review.
AB  - With a significant proportion of HIV-infected patients now presenting with co
      occurring substance abuse disorders and mental disorders, interest in integrated
      HIV care is growing. However, no review of integrated HIV care has been
      conducted. Using relevant key word searches of the Medline and Psychlit
      databases, the authors identified about 450 publications. The few evaluations of
      integrated models tended to focus on measurements of engagement and retention in
      medical care, and their findings indicated an association between integrated HIV
      care and increased service utilization. No random assignment controlled studies
      were identified, except in the peripheral area of integrated care (without HIV
      primary care) for persons with co-occurring substance abuse disorders and mental
      disorders. The majority of reviewed articles described integrated models
      operating in the field and various aspects of implementation and sustainability.
      Overall, they supported use of a wide range of primary and ancillary services
      delivered by a multidisciplinary team that employs a 'biopsychosocial' approach.
      Despite the lack of scientific knowledge regarding the effects of integrated HIV
      care, those wanting to optimize treatment for patients with multiple interacting
      disorders can gain useful and practical knowledge from this literature.

PMID- 15736822
TI  - Recruitment, engagement, and retention of people living with HIV and co-occurring
      mental health and substance use disorders.
AB  - People living with HIV/AIDS who have both a co-occurring mental health diagnosis
      and a substance use disorder (individuals with triple diagnoses) frequently do
      not receive adequate treatment for one or more of their illnesses. Poverty, risky
      behaviours, vacillating motivation, and cognitive impairments are additional
      problems facing many individuals with triple diagnoses. In many communities the
      service system is inadequately prepared to serve this population. Treatment
      barriers include stigma associated with the three illnesses, separate funding
      streams, and lack of co-ordination between medical, mental health, and substance
      abuse treatment facilities. This paper discusses strategies for recruiting,
      engaging, and retaining individuals with triple diagnoses in both treatment and
      research. Recruitment strategies should be directed at both professionals and
      individuals with triple diagnoses themselves. Recruiting and engaging these
      individuals in treatment requires that comprehensive services be provided on a 24
      hour basis in a flexible and culturally competent manner. A team approach is
      often the most effective way of providing such services. Retaining individuals
      with triple diagnoses in a longitudinal research study requires multiple
      strategies including the collection of detailed tracking information, outreach
      workers, and financial incentives for completing the interviews.

PMID- 15736823
TI  - Adherence in people living with HIV/AIDS, mental illness, and chemical
      dependency: a review of the literature.
AB  - Adherence to antiretroviral medications is central to reducing morbidity and
      mortality among people living with HIV/AIDS. Relatively few studies published to
      date address HIV adherence among special populations. The purpose of this article
      is to review the existing literature on HIV antiretroviral adherence, with an
      emphasis on studies among the triply diagnosed population of people living with
      HIV/AIDS, mental illness, and chemical dependency. In order to reflect the most
      current information available, data from conference proceedings, federally funded
      studies in progress, and the academic literature are presented for consideration.

PMID- 15736825
TI  - Economic evaluations of HIV treatment and health research with people diagnosed
      with HIV infection and co-occurring mental health and substance use disorders.
AB  - This paper describes the research challenges involved in measuring costs in
      economic evaluations of patients who are coping simultaneously with HIV/AIDS and
      co-occurring mental health and substance abuse disorders-especially in multi-site
      studies. We describe the general issues that arise in measuring costs for this
      population and suggest some operational solutions for their resolution, drawing
      from our experience in a recent multi-site health services research study focused
      on this population. We show that while reliance on patient self-report data may
      be unavoidable to provide a common denominator in multi-site studies, there are
      also some practical ways of improving the accuracy of such data and the cost
      estimates that result from them. We also provide readers with a means for
      securing the data collection instruments developed for the cost component of this
      study in the hope that these may serve as templates for researchers doing similar
      work.

PMID- 15736824
TI  - Understanding the interface of HIV, trauma, post-traumatic stress disorder, and
      substance use and its implications for health outcomes.
AB  - Many individuals living with HIV have been exposed to some type of traumatic
      event during their lives and may be living with symptoms of post-traumatic stress
      disorder (PTSD). A substantial number of these individuals are also likely to
      show evidence of a co-morbid substance use disorder (SUD). There is reason to
      believe that the co-occurrence of HIV and PTSD or co-morbid PTSD and SUD
      (PTSD/SUD) may predict poorer health outcomes. There are several pathways through
      which PTSD or PTSD/SUD might adversely impact the health of individuals living
      with HIV, including participation in negative health behaviours, low levels of
      adherence to antiretroviral medications, and/or a direct, deleterious effect on
      immune function. Psychological interventions are needed to treat PTSD and
      PTSD/SUD in HIV-positive individuals, and reduce the negative impact of these
      conditions on health outcomes. This article will explore data on the prevalence
      of trauma exposure, PTSD, and PTSD/SUD among individuals living with HIV, the
      pathways through which these conditions might affect health, possible
      interventions for PTSD and PTSD/SUD for individuals living with HIV, and methods
      for integrating care for individuals with these disorders. Future directions for
      research related to HIV, PTSD, and PTSD/SUD will also be discussed.

PMID- 15736826
TI  - Consumer representation in multi-site HIV, mental health, and substance abuse
      research: the HIV/AIDS Treatment Adherence, Health Outcomes and Cost Study.
AB  - Funders of HIV, mental health, and substance abuse research and services are
      increasingly mandating substantial consumer representation in the programmes they
      support. A review of the literature reveals that despite considerable challenges,
      consumer representation in HIV, mental health, and substance abuse research and
      services can be extremely valuable, both for the consumer representatives and the
      programmes they serve. The consumer representation model of the HIV/AIDS
      Treatment Adherence, Health Outcomes and Cost Study is described. Consumer
      representatives and principal investigators are interviewed about their
      experiences working within the model. Their collective comments form the basis of
      recommendations for practice when employing consumer representation models.

PMID- 15736827
TI  - Bioadhesive fluorescent microspheres as visible carriers for local delivery of
      drugs. II: Uptake of insulin-loaded PCEFB/PLGA microspheres by the
      gastrointestinal tract.
AB  - Uptake of novel inherently fluorescent microspheres composed of a luminescent
      polyanhydride, poly[p-(carboxyethylformamido)-benzoic anhydride] (PCEFB), and
      poly(lactide-co-glycolide) (PLGA) (2:1, weight ratio) by the gastrointestinal
      tract was evaluated by fluorescent microscopy. Oral efficiency of the
      incorporated insulin also was determined by measuring reduction of plasma glucose
      levels after feeding diabetic rats with a single dose of the microspheres. We
      found that PCEFB/PLGA microspheres could adhere to the intestinal epithelium and
      traverse the absorptive cells. A large number of the spheres were observed in
      spleen, whereas few were detected in liver within the evaluated period of time.
      Apparent reduction of the plasma glucose levels was observed over a span of 6 h
      postfeeding. The unique properties of the delivery system such as
      biodegradability, bioadhesivity, and inherently luminescent characteristics
      render it an ideal "visible" tracer for monitoring oral fate of polymeric
      microspheres.

PMID- 15736828
TI  - In vitro release of cisplatin from sol-gel processed porous silica xerogels.
AB  - Cisplatin an antineoplastic medicine, was incorporated into a silica gel received
      by the sol-gel method. Various techniques of trapping an active substance in gel
      were applied: at the stage of sol creation--by the predoping method--and already
      upon receipt of hard xerogel--the postdoping method. Further, the research aimed
      at the determination of the dynamics of cisplatin release from sol-gel processed
      silica xerogel to the water phase. Based on the achieved results, we may state
      that the sol-gel method is useful for trapping a medicine like cisplatin in
      silica gel and gives repeatable results with regard to medicine release from the
      pores of the so-established matrix. The postdoping method appeared to be more
      beneficial, because the gained gel's active substance is released almost entirely
      (94-96%). The time of release was 3 days.

PMID- 15736829
TI  - Preparation of arsenic trioxide-loaded microemulsion and its enhanced
      cytotoxicity on MCF-7 breast carcinoma cell line.
AB  - In this study, an injectable microemulsion of arsenic trioxide (As2O3-M) was
      prepared for intratumoral injection and the suppressive effect of As2O3-loaded
      microemulsion on human breast cancer cells MCF-7 was compared with those of a
      solution of the drug. Microemulsion was made up of soybean oil as oil phase, a
      mixture of Brij 58 and Span 80 as surfactants, absolute ethanol as cosurfactant,
      and bidistilled water containing As2O3 solution as the aqueous phase.
      Microemulsion formulation contains 5 x 10(-6) M As2O3. The pH of As2O3-M was
      adjusted to 7.35 +/- 0.1 and the physicochemical stability of the formulation was
      observed. The particle size distribution and zeta potential of As2O3-M were
      measured by Zetasizer 3000 HSA. The mean droplet diameters of As2O3-M were
      determined as 8.6 +/- 0.4 nm. As2O3-M exhibited 13.1 +/- 0.9 mV zeta potential.
      The formulation was physically stable for 12 months at room temperature when kept
      in ampule forms, as well as after autoclaving at 110 degrees C for 30 min. The
      antitumor effects of As2O3-M were examined on human breast cancer cells MCF-7. It
      was clearly demonstrated that As2O3-M had a significant cytotoxic effect on
      breast cancer cell lines, and the cytotoxic effect of As2O3-M was significantly
      more than that of regular As2O3 solutions. Even approximately 3000 times diluted
      microemulsion formulation loaded with 5 x 10(-6) M As2O3 showed a cytotoxic
      effect. As a result, this diluted concentration (approximately 1.6 x 10(-9) M)
      was found 1000 times more effective than regular As2O3 solutions (5 x 10(-6) M).
      According to the in vitro cytotoxicity studies, we concluded that when As2O3 was
      incorporated into the microemulsion (As2O3-M), which is a new drug carrier
      system, it suppresses tumor cell growth on multiple tumor lines. These results
      indicate that As2O3-M may exert a low cytotoxic effect on normal cells and may be
      effective as an antitumor agent that induces apoptosis.

PMID- 15736830
TI  - New synthetic glycolipids for targeted gene transfer: synthesis, formulation in
      lipoplexes and specific interaction with lectin.
AB  - Nonviral gene delivery systems are a promising approach for gene therapy
      applications, despite their low in vivo gene transfer efficiency. One approach to
      enhance this efficiency is to incorporate targeting elements into cationic
      lipid/DNA complexes (lipoplexes). Ligand-containing lipoplexes have to retain
      their efficiency while exposing accessible ligand on their surface.
      Physicochemical properties (particle size, surface charge, and efficacy of DNA
      complexation) of the lipoplexes largely determine their gene transfer efficiency.
      We synthesized glycolipids with various galactosylated head ligand and
      incorporated them into lipoplexes. We showed that incorporation of up to 33% mol
      of glycolipid did not change the physicochemical properties of lipoplexes. Some
      of our glycolipids yielded lipoplexes whose galactosyl heads were well exposed on
      the surface as demonstrated by a strong interaction with Ricinus communis
      agglutinin. Glycolipid-containing lipoplexes gave an efficient gene transfer on
      hepatocytes, although no ligand-targeted transfection could be observed.

PMID- 15736831
TI  - Preparation of various solid-lipid beads for drug delivery of enrofloxacin.
AB  - Solid-lipid beads were prepared to retard the release rate of enrofloxacin and to
      mask its bitter taste using carrageenan or sodium alginate as a shell material
      and either cacao butter or Witepsol W-35 as a solid lipid core. Sodium alginate
      was a better shell material than carrageenan and the highest loading efficiency
      was obtained using 2% sodium alginate. The alginate beads had a spherical
      morphology and a sturdy shell structure. The enrofloxacin release rate at room
      temperature was greatly reduced. Solid-lipid beads have the potential to mask the
      bitter taste of enrofloxacin and extend its release rate.

PMID- 15736832
TI  - Gellan-based scleral implants of indomethacin: in vitro and in vivo evaluation.
AB  - Film-type scleral implants of indomethacin with gellan gum were prepared by
      solvent casting and evaluated for uniformities of thickness, weight, drug
      content, and surface pH. The effect of plasticizers like glycerol, propylene
      glycol (PG), and polyethylene glycol 200, and 400 on the void volume of free
      gellan films (placebo) was calculated from the water content of the films. The
      drug release from the prepared implants was determined using a static dissolution
      set-up developed and optimized in our laboratory. Based on the results of the
      void volume and initial drug release studies, glycerol and PG were selected as
      the plasticizers for the gellan-based implants. The morphology of the drug-free
      films (containing 10% and 40% of PG) and the drug-loaded films (before and after
      dissolution and crosslinked) was studied using scanning electron microscopy.
      Further, the effect of plasticizer concentration, gellan concentration, effect of
      crosslinking technique, and duration of crosslinking using calcium chloride on in
      vitro drug release characteristics were evaluated. Selected batches of the
      implants were subjected to pharmacodynamic studies, after scleral placement, in
      uveitis-induced (intravitreal injection of bovine serum albumin 50 microg/ml)
      rabbit eyes. The release of indomethacin from the prepared implants followed
      matrix diffusion kinetics with diffusion co-efficient (n) values ranging between
      0.358 to 0.708 and seemed to depend on both gellan and plasticizer concentration.
      Surface crosslinking with 10% calcium chloride for 8 hr retarded drug release
      (1.42 times less than noncrosslinked implant) and was optimum. The
      pharmacodynamic studies showed a marked improvement in the various clinical
      parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in
      the implanted eye compared with the control eye in the rabbits. The scleral
      implants survived up to 3 weeks in vivo.

PMID- 15736834
TI  - Practical fluoride and remineralization protocols for adult patients.
AB  - There is a wealth of information on preventive measures and procedures that can
      be used to care for paediatric and adolescent patients. However, few studies have
      been conducted in adult or geriatric populations, and an understanding of
      preventive and non-surgical treatment regimens for these patients is lacking.
      Traditionally, caries incidence is high among risk groups of low income, low
      dental IQ and certain ethnic subgroups, but we are now witnessing a high
      incidence of caries among middle-income and healthy adult patients with an
      imbalance of protective factors and cariogenic factors. We will direct our
      attention to the adult population and attempt to address some of the most common
      questions.

PMID- 15736833
TI  - Synthesis, characterization and evaluation of IPN hydrogels for antibiotic
      release.
AB  - We prepared new ternary interpenetrating polymeric networks (IPN) systems
      containing chitosan, poly(N-vinylpyrrolidone) and poly(acrylamide) polymers. IPNs
      were synthesized by radical polymerization of acrylamide monomers in presence of
      glutaraldehyde (G) and N,N'-methylenebisacrylamide as crosslinkers and the other
      polymers. These IPNs were named as C-P-A. Glutaraldehyde were used in different
      concentration to control the network porous of IPNs. Spectroscopic and thermal
      analyses of these cylindrical shaped IPNs were made with fourier transform
      infrared spectroscopy analysis, thermogravimetric analysis, and thermomechanical
      analysis. Swelling studies of IPNs were carried out at pH 1.1 and pH 7.4 at 37
      degrees C. The swelling and diffusion parameters of IPNs in these solutions were
      calculated. Amoxicillin as a bioactive species was entrapped to the IPNs during
      synthesis. In vitro release kinetics of IPNs were investigated. The experimental
      data of swelling and release studies suggest clearly that the swelling and
      release process obeys second-order kinetics. The release of the entrapped
      bioactive species from IPNs depends on the degree of crosslinking of the polymer
      and pH of the medium at body temperature. We observed that amoxicillin release at
      pH 1.1 was higher than at pH 7.4. As a result, IPNs-based chitosan with different
      cross-linker concentration could be promising candidates for formulation in oral
      gastrointestinal delivery systems.

PMID- 15736835
TI  - The PDA and the oral maxillofacial surgeon.
AB  - The personal digital assistant (PDA) offers clinicians the ability to enter and
      manage clinical information at the point of care. The first part of this series
      examined the oral medicine and surgery resources available on the Internet. This
      article discusses the possibilities of PDA technology, in conjunction with the
      Internet, for oral maxillofacial surgeons to enhance their clinical practice.

PMID- 15736836
TI  - Role of interceptive orthodontics in early mixed dentition.
AB  - Early orthodontic interventions are often initiated in the developing dentition
      to promote favourable developmental changes and remove or suppress those that are
      unfavourable. Early interceptive orthodontics can eliminate or reduce the
      severity of a developing malocclusion, the complexity of orthodontic treatment,
      overall treatment time and cost. It also improves self-esteem in the subjects and
      parental satisfaction. Early detection and appropriate referral of cases
      requiring interceptive orthodontics are important. However, lack of awareness
      among school children, parents and primary-care personnel (dental nurses and
      dental officers) may result in patients not being referred for timely
      interceptive intervention. This article presents a general view of the scope of
      interceptive orthodontics that can be carried out in early mixed dentition, i.e.
      when the permanent incisors and molars are erupting into the oral cavity.

PMID- 15736837
TI  - Principles and implications of site preservation for alveolar ridge development.
AB  - The extraction of a tooth normally results in the loss of ridge height and width.
      Often, clinicians are faced with the management of edentulous sites that are less
      than optimal for prosthetic rehabilitation and implant restoration due to
      considerable alveolar ridge collapse after tooth removal. Site preservation using
      bone grafts or substitutes with and without a membrane maintain ridge dimensions
      and contours. However, some clinicians believe that such procedures are over
      treatment. This paper reviews the concepts and indications for site preservation
      following tooth extraction for the purpose of facilitating implant placement and
      conventional prosthetic restoration.

PMID- 15736838
TI  - Early childhood caries: an update.
AB  - Early childhood caries is the currently accepted term used to describe dental
      caries occurring in infants and toddlers. It is a multifactorial, transmissible
      and infectious disease that has recently been under scrutiny in the literature.
      The microflora, substrate, saliva and host are key factors involved in the
      pathogenesis, together with the immature host defence system and developing
      bacterial flora. Immature enamel surfaces and developmental defects of enamel
      should also be considered in the aetiology. This paper addresses the
      controversies of the cariogenicity of bovine milk, human breast milk and infant
      formulas. Clinical management should be planned according to age, extent of
      lesions, compliance of primary caregivers and where treatment is rendered
      (private or public sector). Cases of early childhood caries need comprehensive
      restorative management and preventive treatment together with the help of other
      health care professionals.

PMID- 15736839
TI  - Oral health status of 16-year-old school children in Malaysia.
AB  - The aim of the present study was to determine the oral health status of 16-year
      old Malaysian school children. The prevalence of caries was 75.5%. More than 60%
      of subjects had caries experience by teeth (DMFT) scores of 0-3. The largest
      component of the DMFT and caries experience by surface index was the filled
      component. Females had higher caries prevalence and caries scores than males. The
      mouth and tooth prevalences of enamel defects were 56% and 21.8%, respectively.
      The most common type of enamel defects observed were diffuse opacities, affecting
      95.5% of affected subjects and 92.1% of affected teeth. One-third of subjects had
      healthy gingival conditions, 8.6% had bleeding gingivae, 55.1% had calculus and
      3% had pockets. Less than 1% of subjects wore or required dentures. Cleft lip
      and/or palate was uncommon. This study shows that the prevalence of caries and
      DMFT scores have declined over the last 30 years.

PMID- 15736841
TI  - Absence of apical resorption during orthodontic treatment on a tooth with a
      complicated crown fracture and root canal treatment: a case report.
AB  - Root resorption often occurs after tooth trauma and may also occur during
      orthodontic tooth movement. This has been attributed to bacteria and inflammation
      or a combination of both aetiologies. The literature suggests that root canal
      treatment performed on a traumatized tooth that will concurrently or subsequently
      undergo orthodontic tooth movement may forestall the resorptive process. This
      case report provides evidence for this prevention and discusses the hypothesis
      for the absence of resorption on root-treated teeth.

PMID- 15736840
TI  - Polish retention of new aesthetic restorative materials over time.
AB  - New aesthetic restorative materials claiming superior polish retention have
      recently been introduced. This study compared polish retention of eight different
      types of aesthetic restorative materials including ormocer and nanofill
      composites over a 6-month ageing period in distilled water. Eight specimens of
      each material were fabricated and roughened with 320 grit grinding paper using a
      lapping device and finished/polished with a graded abrasive disk system. Mean
      roughness was then determined using a surface profilometer. The specimens were
      then stored in distilled water at 37 degrees C and roughness measurements were
      repeated after 3 and 6 months of ageing. Mean surface roughness values ranged
      from 0.15 to 0.68 microm for immediate readings and 0.17 to 1.02 microm after
      ageing for 6 months. With the exception of the highly viscous glass ionomer
      cement, the surface polish of most materials did not deteriorate much over time.
      At all time intervals, composite materials based on ormocer and nanomer
      technology were significantly smoother than all other materials evaluated.

PMID- 15736843
TI  - Use of the apically repositioned flap in the management of labially impacted
      maxillary central incisors.
AB  - Management of labially impacted maxillary central incisors often requires a
      coordinated surgical and orthodontic approach. In such cases, the treatment
      objective is surgical exposure of the unerupted incisor, preferably with a
      functional width of keratinized gingiva on the labial surface. Tooth exposure is
      then followed by orthodontic intervention to move the tooth to the line of
      occlusion. This paper describes three cases where the apically repositioned flap
      technique was used to manage labially impacted maxillary central incisors.

PMID- 15736842
TI  - Management of the infected, abscessed primary tooth--a report.
AB  - Despite modern advances in the prevention of dental caries and an increased
      understanding of the importance of maintaining the natural dentition in children,
      many abscessed and infected primary teeth, especially the deciduous molars, are
      still being prematurely lost through extractions. This report describes a simple,
      quick and effective technique that has been successfully used to manage infected,
      abscessed primary teeth. Results indicate that the non-vital primary pulp therapy
      technique is both reliable and effective. Not only is the procedure painless, it
      also helps to relieve the child of his immediate pain and achieves the primary
      goals of elimination of infection and retention of the tooth in a functional
      state without endangering the developing permanent tooth germ.

PMID- 15736844
TI  - Guidelines for root canal treatment.

PMID- 15736845
TI  - Pedological characterisation of sites along a transect from a primary
      cadmium/lead/zinc smelting works.
AB  - A pedological characterisation of seven sites along a transect from a smelter at
      Avonmouth, UK, was undertaken. Site locations comprised a mixture of both
      grassland (5 sites) and oak tree dominated (2 sites) areas. Geographically, sites
      were either low lying or on adjacent elevated ground. Across the transect, a
      severe gradient of metal concentrations was found with highest values for organic
      soil horizons from close to the factory. Comparisons with quality standards
      indicate that these metal levels are likely to be a major ecological stressor. In
      addition to the strong metal gradient, a number of other between site differences
      were also observed. These were firstly water regime, which at the low lying sites
      close to the smelter showed influence by both, groundwater and stagnant water,
      while at more distant sites indicated susceptibility to stagnant water only, and
      secondly soil pH, which showed large between site variations, although no
      consistent trend along the transect. Humus forms at sites more than 1.5 km from
      the smelter were characteristic for the soil conditions and land-use present,
      while those at sites within 1.5 km showed disturbed profiles. Indeed, the humus
      types present at these locations suggest that the activity of soil invertebrates
      may be inhibited. This is almost certainly due primarily to the high
      concentrations of metals that were present in mineral soil and organic horizons
      at the sites. However, the potential influences of water regime and pH could also
      be relevant factors influencing the results of any further studies conducted at
      these study sites.

PMID- 15736848
TI  - Genetic variation in the enzyme esterase, bioaccumulation and life history traits
      in the earthworm Lumbricus rubellus from a metal contaminated area, Avonmouth,
      England.
AB  - Earthworms, Lumbricus rubellus, were collected in three successive years, 1997,
      1998 and 1999 from 5, 6 and 4 sites, respectively, along a metal gradient near a
      smelter at Avonmouth, England. In total 271 worms were collected, 47 in 1997, 97
      in 1998, and 127 in 1999. The worms were analysed for the enzyme esterase by
      means of agarose electrophoresis and for internal metal concentration. At one
      site collected in three successive years, 64 individuals of 66 were heterozygous
      for the esterase enzyme. The metal concentrations (Cu and Zn) in worms were
      significantly correlated with the total concentration and the CaCl2 extractable
      fraction of the metal in the soil. One of the homozygous esterase genotypes was
      significantly correlated with distance from the smelter, the extractable fraction
      of metals from soil, and the metal concentration in the worms. The other
      homozygous genotype was correlated with the CaCl2 extractable Cu and the Cu
      concentration in the worms. The internal levels of Cd, Cu, and Zn showed a higher
      classification potential (Discriminant Analysis) for 50 of 127 individuals,
      collected in 1999, when based on the original habitat of the earthworms than on
      the esterase genotype. The remaining 77 specimens, representing three sites, were
      exposed for 30 days in the laboratory to soils from four sites. For the
      individuals in this transplantation experiment, parameters measured were the
      esterase phenotype, internal metal concentration (Cd, Cu, and Zn), mortality, wet
      weight change, cocoon production, and cocoon hatching success. Cocoon production
      was highest among the worms from the most contaminated area, while worms from the
      least contaminated area had the highest hatching success. Neither the metal
      concentrations, in soil or internal, nor the life-history parameters could fully
      explain the genotypic distribution of esterase along the gradient. The internal
      concentrations of Cd, Cu and Zn in the worms used for the transplantation
      experiment showed the highest classification potential (Discriminant Analysis)
      when the prediction was based on the original habitat of the earthworms. The
      classification potential was less strong when based on esterase genotype and
      least on the transplantation conditions. Including life history traits did not
      enhance the prediction potential.

PMID- 15736846
TI  - Stress proteins (hsp70, hsp60) induced in isopods and nematodes by field exposure
      to metals in a gradient near Avonmouth, UK.
AB  - Heat shock proteins (hsps) are potential biomarkers for monitoring environmental
      pollution. In this study, the use of hsps as biomarkers in field bioassays was
      evaluated in terrestrial invertebrates exposed to a metal gradient near
      Avonmouth, UK. We investigated the hsp70 response in resident and transplanted
      isopods of the species Oniscus asellus and Porcellio scaber and the hsp60
      response in transplanted nematodes of the species Plectus acuminatus in six field
      sites along the metal gradient. Considerable differences were detected in the
      stress responses between nematodes and isopods (isopods responded in a gradient
      specific manner, nematodes did not), the two isopod species and the transplanted
      and resident specimens of each isopod species: in the sites closest to the
      smelter, O. asellus residents showed high hsp70 levels while O. asellus
      transplanted from an unpolluted site displayed comparatively low hsp70 levels.
      For P. scaber, it was just the opposite. In resident isopod populations of both
      species, tolerant phenotypes were revealed in the most contaminated field sites.
      The hsp70 level in both isopod species was a suitable biomarker of effect (but of
      exposure only in non-tolerant individuals) even in long-term metal-contaminated
      field sites. The hsp60 response in the nematode alone was not a suitable
      biomarker for heavily contaminated soils. However, it had indicative value when
      related to the hsp70 response in the isopods and could be a suitable biomarker
      for less heavily contaminated soils.

PMID- 15736847
TI  - Cd accumulation and Cd-metallothionein as a biomarker in Cepaea hortensis
      (Helicidae, Pulmonata) from laboratory exposure and metal-polluted habitats.
AB  - Cepaea hortensis is a widespread terrestrial pulmonate, contributing
      significantly to element fluxes in soil ecosystems. Due to its capacity of
      accumulating certain trace elements in its tissues, Cepaea hortensis can serve as
      a biological indicator of metal accumulation in contaminated areas. In response
      to Cd exposure this species and related helicid pulmonates are also able to
      synthesize an inducible, Cd-binding metallothionein (MT) isoform specifically
      serving in binding and detoxification of this metal. As shown by field-collected
      garden-snails from a metal-contaminated site near a zinc smelting works in
      Avonmouth (UK) and an unpolluted reference site in Reutte (Tyrol, Austria), Cd
      and Cd MT concentrations in midgut gland of C. hortensis from these sites
      increased with rising Cd concentrations in the soil substrate from the same
      contaminated sites. By combining the results of these field data with laboratory
      experiments it appears that midgut gland Cd-MT of Cepaea hortensis seems to
      fulfil the criteria of a successful biomarker in many respects. First, the
      synthesis of the protein can rapidly be induced by Cd exposure. Second, the level
      of Cd MT induction in C. hortensis directly reflects the intensity of metal
      exposure. Third, the induced signal of increased Cd-MT concentration in C.
      hortensis is persistent over extended periods of time. Fourth, the Cd-MT signal
      in C. hortensis seems to be very specific for Cd exposure. Regression analyses
      demonstrate that tissue levels of Cd and Cd MT in C. hortensis depend on Cd
      concentrations in the substrate which is represented by either soil or plant
      material on which snails normally feed. In both cases the best fit for this
      dependence is exhibited by a semi-logarithmic relationship, with substrate (soil
      or plant feed) concentrations expressed on a logarithmic scale. It is concluded
      that C. hortensis and other related pulmonates can successfully be used either as
      biological indicators of Cd accumulation, or as key species in biomonitoring
      studies focusing on Cd-MT induction as a biomarker for Cd exposure.

PMID- 15736849
TI  - Energy reserves and metal-storage granules in the hepatopancreas of Oniscus
      asellus and Porcellio scaber (Isopoda) from a metal gradient at Avonmouth, UK.
AB  - Isopods taken from populations of Onsicus asellus and Porcellio scaber from long
      term polluted sites in the vicinity of metal smelting works at Avonmouth, South
      West England, and from a control site near Tubingen, South Germany, were examined
      for the frequency and size of metal-containing granules (spherites), lipid
      droplets and glycogen in their hepatopancreas. The number and size of spherites
      in the hepatopancreas of O. asellus increased with decreasing distance to the
      smelter, but such a trend was not found in P. scaber. A trend towards massive
      reduction in hepatopancreatic energy reserves (lipid, glycogen) with increasing
      soil metal pollution was observed for O. asellus while, in contrast, the lipid
      and glycogen content of P. scaber midgut gland cells was independent of the
      distance to the smelter. In view of previous reports on metal accumulation and
      biochemical responses to metal pollution, we propose that the two investigated
      isopod species, which form stable populations in the Avonmouth metal gradient,
      use different strategies to survive.

PMID- 15736850
TI  - Environmental metabonomics: applying combination biomarker analysis in earthworms
      at a metal contaminated site.
AB  - Earthworms were taken across an environmental gradient of metal contamination for
      ecotoxicology assessment. Both indigenous (Lumbricus rubellus and L. terrestris)
      and introduced earthworms (Eisenia andrei, exposed in mesh bags) were studied.
      Changes in the levels of small molecule metabolites in earthworm tissue extracts
      were analysed by 1H NMR spectroscopy as a means of identifying combination
      biomarker compounds. Principal components analysis of the NMR spectral data
      revealed that biochemical changes were induced across the metal contamination
      gradient. Native worms (L. rubellus) from the most polluted sites were associated
      with an increase in the relative concentration of maltose; a decrease was also
      seen in the concentration of an as yet unidentified biomarker compound.
      Introduced worms (E. andrei) did not show differences to the same extent. Direct
      integration of the resonances from histidine and 1-methylhistidine showed that
      relative histidine concentrations were elevated slightly for L. rubellus,
      confirming the results of earlier mesocosm studies. Conversely, the relative
      concentrations of both histidine and 1-methylhistidine were greatly reduced by
      metal contamination in L. terrestris. This study demonstrates the utility of NMR
      spectroscopy in detecting previously unknown potential biomarkers for ecotoxicity
      testing and identified maltose as a potential biomarker compound deserving of
      further study.

PMID- 15736851
TI  - Metal effects on soil invertebrate feeding: measurements using the bait lamina
      method.
AB  - Heightened concerns regarding the protection of terrestrial ecosystems at a
      national level has increased the need to develop a suite of indicators capable of
      assessing the quality, integrity and fertility of soils. Of the assays currently
      available, tests that measure aspects of soil function and associated parameters
      are among the most promising, since these integrate effects on soil quality at
      the highest level of organisation. In this study we describe results of the
      deployment of an indicator of soil functional integrity (the bait lamina test)
      that is designed to measure the feeding activity of soil invertebrates. Bait
      lamina was used at six grassland sites located along a transect from a smelter at
      Avonmouth (South-West England) used in the EU funded BIOPRINT II project. Results
      indicated highest bait removal (feeding) at sites furthest from the factory,
      intermediate feeding activity at intervening sites and extremely low activities
      at the two sites closest to the smelter. The strong decline in activity for the
      group of sites closest to the smelter corresponded with increasing metal
      concentrations suggesting a clear impact of metals on detritivorous invertebrate
      feeding. Comparisons of the results of the bait lamina study to previous
      invertebrate survey work suggested that the differences in observed bait removal
      can be attributed to direct effects of metals on the abundance and biodiversity
      of key decomposer groups such as earthworms, isopods, molluscs, myriapods,
      springtails and mites.

PMID- 15736853
TI  - Hydrogen peroxide production by Mycoplasma bovis and Mycoplasma agalactiae and
      effect of in vitro passage on a Mycoplasma bovis strain producing high levels of
      H2O2.
AB  - Hydrogen peroxide (H2O2) production and oxygen uptake during the oxidation of
      NADH and L-alpha-glycerophosphate (GP) by lysed cells was determined for the type
      and field strains of Mycoplasma bovis and M. agalactiae. NADH oxidation by all
      the strains showed variable production of H2O2 ranging from 0 to 1.21 mol/mol O2
      taken up. All strains were unable to oxidize GP, showing absence of GP oxidase
      activity. Some strains were identified that produced relatively high levels of
      H2O2 (> 1.0 mol/ mol O2 taken up). In vitro passage of M. bovis strain 119B96
      showed reduced H2O2 production: 0.52, 0.16, and 0.07 mol/mol O2 taken up after
      the 50th, 100th and 200th passages, respectively. SDS-PAGE analysis showed the
      loss of a protein band of 32 kDa after 50 passages. These preliminary studies
      show that not only does H2O2 production by potentially pathogenic Mycoplasma spp.
      vary in the field but also that similar alterations can be induced by passage in
      culture. In the latter case, at least in one M. bovis strain, this alteration has
      been shown by SDS-PAGE to be associated with a loss of specific protein
      production. Further study of these phenomena is essential background for the
      production of more efficient vaccines for mycoplasmas.

PMID- 15736852
TI  - Critical analysis of soil invertebrate biomarkers: a field case study in
      Avonmouth, UK.
AB  - During the period 1996-1999 a joint field research programme (BIOPRINT-II) funded
      by the European Union was undertaken. The main objective of this project was the
      deployment of biochemical fingerprint techniques of soil invertebrate biomarkers
      for assessing the exposure and effect of toxicants on soil invertebrates in the
      field. The aim was to apply these techniques in the field focusing on a a
      chronically polluted field near a lead and zinc smelter in Avonmouth (UK).
      Therefore six sites were selected from which organisms were either sampled or
      transplanted to or from the laboratory. The project has provided a unique
      opportunity to apply a series of biological test methodologies in order to
      determine the hazard posed to soil sustainability and by inference soil
      biodiversity and function. This work has attempted to understand the linkage
      between effects measured at the molecular or cellular level and relate these to
      changes at higher levels of biological organisation. Here we evaluated the links
      between biomarkers and soil function parameters. The paper aims to summarize and
      explore the necessary caveats that must be understood before soil biomarker test
      systems may be used to strengthen the risk assessment process.

PMID- 15736854
TI  - Immunogenicity of major cell surface protein(s) of Brucella melitensis Rev 1.
AB  - Brucella melitensis Rev 1 organisms were salt-extracted and the cell surface
      proteins (BCSPs) were found to be mainly 39-42 kDa (group 2 porin proteins) in
      addition to 31.6, 32.5, 58.5 and 14.7 kDa proteins. DEAE-Sephadex anion-exchange
      column chromatography of BCSPs yielded fraction 1, which contained one major
      protein (39.8-42.0 kDa) and a minor protein (31.6 kDa). All these proteins were
      found to be immunogenic by Western blotting. Fraction 1 along with monophosphoryl
      lipid A and trehalose dicorynomycolate adjuvants as well as BCSPs alone induced
      significant (p < or = 0.05) protection in BALB/c mice. Both these immunizing
      agents produced almost equivalent protection to live B. melitensis Rev 1 vaccine
      at 15 and 30 days post challenge. Lymphocyte stimulation test as well as delayed
      type hypersensitivity reaction revealed that both these preparations induced cell
      mediated immune response. These preparations also induced humoral immune response
      as indicated by indirect ELISA. Neither of the immune responses was significantly
      less (p < or = 0.05) than that with live B. melitensis Rev 1 vaccine, except that
      their duration was short.

PMID- 15736855
TI  - Effects of cyclosporin A on blood pressure, baroreceptor reflex and renal
      function in dogs.
AB  - The objective of this study is to investigate the effect of cyclosporin A (CsA)
      on baroreceptor reflex and renal function. Fifteen male mongrel dogs weighing 13
      18 kg were divided into three groups and were treated orally as follows: group 1,
      enalapril 0.5 mg/kg per day for 10 days; group 2, CsA 20 mg/kg per day for 7
      days; group 3, enalapril 0.5 mg/kg per day for 3 days combined with CsA 20 mg/kg
      per day for 7 more days. Measurements of blood pressure and of baroreflex
      response to sodium nitroprusside (SNP) and phenylephrine (PE) and renal function
      studies were performed on the days before and after receiving drugs. In group 1,
      both systolic arterial pressure (SAP) and mean arterial pressure (MAP) were
      unaltered, while diastolic arterial pressure (DAP) was reduced significantly. In
      group 2, all pressures (SAP, MAP and DAP) increased significantly. Group 3 showed
      no change in blood pressure. Studies of baroreceptor reflex showed that only dogs
      in group 2 had decreased sensitivity to PE without changing the setpoint. No
      change of the reflex was found in other groups. Renal function studies were
      unaltered in all groups. The data indicate that CsA increased blood pressure,
      which may be due to decreased baroreceptor reflex sensitivity mediated via
      activation of the renin-angiotensin-aldosterone system.

PMID- 15736856
TI  - Basic concepts of the bovine teat canal.
AB  - The bovine teat canal is highly specialized in its unique function of preventing
      both leakage of milk and entry of bacteria and thereby plays a major role in the
      defence of the udder against mastitis. The teat canal is a longitudinally folded
      cylinder-shaped body opening, covered with approximately the same type of
      epithelia as the normal skin and surrounded with a net-like integrated
      musculoelastic system facilitating its opening and closure. During milking, dead,
      flattened, enucleated squamae (cellular detritus) are sloughed from the teat
      canal surface and are continually replaced by inner cells differentiating
      outwards. The epidermis is characterized by a polarized pattern of epithelial
      growth and differentiation, with a single layer of proliferating keratinocytes
      and multiple overlying differentiated layers. Morphologically, the cells transit
      from the basal layers on the basement membrane of the dermis through stratum
      corneum before they finally end up as the keratin of the teat canal. The majority
      of the epidermal protein synthesizing machinery is devoted to making keratin.
      This is reflected in the fact that keratins are the major structural proteins,
      constituting up to 85% of a fully differentiated keratinocyte. Epidermal keratin
      is a 40-70 kDa alpha-helical coiled-coil dimer of the intermediate filament
      family that, among other marker proteins, characterizes each stage of
      keratinocyte differentiation. Studies of skin fragility disorders show that the
      primary role of keratins in epidermal cells is to reinforce them so that they do
      not lyse upon physical pressure and to provide cells with subtly different
      properties of resistance and plasticity to equip the epithelial cells for the
      physical stress of each particular body site. Epithelial cell specialization for
      function also depends, however, on the lipid composition and organization and on
      the epidermal architecture. Epidermal architecture depends on epidermal turnover
      time, which in turn depends on cell number as well as the proliferative
      condition. Both in vitro and in vivo studies have implicated calcium as a major
      modulator of epidermal differentiation. Calcium is a factor known to enhance
      differentiation and promote expression of the differentiation-specific keratin
      genes. In animals and humans, both topical and systemic retinoids produce
      acanthosis, hypergranulosis and a relative (but not absolute) decrease in the
      thickness of the stratum corneum. Despite a high degree of epithelial
      specialization, we expect a somewhat similar immunological functional importance
      in the teat canal epithelia as in other stratified squamous keratinized type
      epithelia.

PMID- 15736857
TI  - Gentamicin nephrotoxicity--a comparison of in vitro findings with in vivo
      experiments in equines.
AB  - The aminoglycoside gentamicin is often used in equine practice. Despite its
      clinical use, concerns remain regarding the potential toxic side-effects, such as
      nephrotoxicity, in equine patients, particularly after repeated dosing. The aim
      of the study was to investigate first in vitro the mechanisms contributing to the
      renal toxicity of gentamicin and to identify sensitive biomarkers indicating
      proximal tubule damage. To this end, the kidney-derived cell lines LLC-PKI and
      MDCK were treated with gentamicin at different concentrations. Toxicity was
      assessed by measuring the release of gamma-glutamyl transferase (GGT), and the
      production of reactive oxygen species (ROS). Cell viability was measured using
      Alamar blue (AB) and Neutral red (NR) cytotoxicity assays. Gentamicin exerted a
      dose-dependent toxicity. Primarily, loss of brush border membrane integrity,
      indicated by GGT leakage, and an increased ROS production were observed. As GGT
      was found to be a sensitive marker for gentamicin-induced renal cell injury, in
      the subsequent in vivo experiments, in which ponies were given gentamicin (3.0
      mg/kg bw three times daily and 4.5 mg/kg bw twice daily) for five consecutive
      days, plasma levels and the urinary excretion of GGT and creatinine were measured
      and the GGT:creatinine ratio was calculated. Elevated GGT levels in urine
      following gentamicin therapy were observed, but this enzyme leakage was transient
      and returned to baseline values after cessation of therapy. It could thus be
      concluded that even a conservative dose regimen of gentamicin did not result in
      significant renal toxicity in healthy ponies.

PMID- 15736858
TI  - Detection of porcine circovirus type 2, porcine parvovirus and porcine
      pseudorabies virus from pigs with postweaning multisystemic wasting syndrome by
      multiplex PCR.
AB  - Multiplex PCR was established to detect porcine circovirus type 2 (PCV-2),
      porcine parvovirus (PPV) and porcine pseudorabies virus (PRV) and applied to
      samples from 137 piglets exhibiting clinical signs of postweaning multisystemic
      wasting syndrome (PMWS). PCV-2 DNA was detected from all samples. Moreover, 43
      samples were positive for PPV but negative for PRV; 11 samples were positive for
      PRV but negative for PPV; and 35 samples were positive both for PPV and PRV.
      These results suggests that PCV-2 co-infection with PRV and PPV may play an
      important role in PMWS. Also, multiplex PCR is an appropriate candidate method
      for diagnosis of PCV-2, PRV and PPV simultaneously in field cases.

PMID- 15736859
TI  - Basidiomycete mycelia in forest soils: dimensions, dynamics and roles in nutrient
      distribution.
AB  - Basidiomycete mycelia are ubiquitous in forest soils where they fulfil a range of
      key ecological functions. Population studies, based largely on basidiome
      collections, indicate that mycelia of many ectomycorrhizal and saprotrophic
      basidiomycetes can spread vegetatively for considerable distances through soil,
      but the extent to which these become physically or physiologically fragmented is
      unclear. This review considers aspects of the distribution, dynamics and
      translocatory activities of individual basidiomycete mycelia in forest soil,
      highlighting current gaps in our understanding and possible ways to address
      these.

PMID- 15736860
TI  - Disintegration of the Micareaceae (lichenized Ascomycota): a molecular phylogeny
      based on mitochondrial rDNA sequences.
AB  - The phylogeny of the family Micareaceae and the genus Micarea was studied using
      mitochondrial small subunit ribosomal DNA sequences. Phylogenetic reconstructions
      were performed using Bayesian MCMC tree sampling and a maximum likelihood
      approach. The Micareaceae in its current sense is highly heterogeneous, and
      Helocarpon, Psilolechia, and Scutula, all thought to be close relatives of
      Micarea, are shown to be only distantly related. The genus Micarea is
      paraphyletic unless the entire Pilocarpaceae and Ectolechiaceae are included, as
      also indicated by an expected likelihood weights test. It is suggested that the
      Micareaceae is reduced to synonymy with the Pilocarpaceae, which also includes
      the Ectolechiaceae, and that Micarea may have to be divided into a series of
      smaller genera in the future. Micarea species with a 'non-micareoid' photobiont
      group with Psora and the Ramalinaceae, whereas Micarea intrusa appears to belong
      in Scoliciosporum. Three species fall inside the paraphyletic Micarea:
      Szczawinskia tsugae, Catillaria contristans, and Fellhaneropsis vezdae. Tropical
      foliicolous taxa are nested within groups of mainly temperate and arctic-alpine
      distribution. A 'micareoid' photobiont appears to be plesiomorphic in the
      Pilocarpaceae but has been lost a few times.

PMID- 15736862
TI  - Towards a phylogenetic classification of Cordyceps: ITS nrDNA sequence data
      confirm divergent lineages and paraphyly.
AB  - The ascomycetous genus Cordyceps accommodates endoparasitic species that attack
      arthropods or other fungi. Analyses of ITS nrDNA sequence data of 72 taxa from
      the teleomorph genera Cordyceps, Claviceps, Epichloe, and the anamorph genera
      Akanthomyces, Beauveria, Metarhizium, Hirsutella, Hymenostilbe, Paecilomyces,
      Polycephalomyces, and Tolypocladium assigned the taxa to four main evolutionary
      lineages not reflected in the current classification of Cordyceps. Ten subclades
      were recognized from separate analyses of data subsets. Judged from the ITS
      phylogenies, Cordyceps spp. with branched stromata were highly supported as a
      divergent lineage. Host specificity was found to be of limited phylogenetic
      significance, and several host shifts are suggested to have occurred during the
      evolution of Cordyceps. Similar ascospore morphology was not reflected in the
      phyletic groups, and closely related taxa showed large interspecific variation
      with respect to the number of segments in which the ascospores are divided.
      However, combinations of selected characters were found to delimitate some
      lineages, e.g. all Cordyceps spp. that attack hosts in the insect orders
      Coleoptera and Lepidoptera, and with non-immersed perithecia and clavate to
      acicular, brightly yellowish to reddish stromata, constituted a separate clade.
      Furthermore, all Cordyceps spp. with perithecia obliquely immersed in the stroma
      were recognized as a distinct monophyletic group. This clade is additionally
      characterized by the formation of anamorphs ascribable to the genus Hymenostilbe.
      The mycogenous Cordyceps spp. grouped in a separate subclade, interspersed by two
      cicadaen parasites and all Tolypocladium spp. except T. parasiticum.
      Tolypocladium and Beauveria were found to be polyphyletic. The included Claviceps
      and Epichloe taxa appeared to be derived within Cordyceps, thus making Cordyceps
      paraphyletic as suggested in other studies.

PMID- 15736863
TI  - Marchandiomyces lignicola sp. nov. shows recent and repeated transition between a
      lignicolous and a lichenicolous habit.
AB  - The anamorphic basidiomycete genus Marchandiomyces presently includes two common
      lichenicolous (lichen-inhabiting) species, M. corallinus and M. aurantiacus
      (teleomorph Marchandiobasidium aurantiacum). We describe here a new species, M.
      lignicola sp. nov., that is similar to M. corallinus in the colour of its
      sclerotia, but differs in having a wood-inhabiting (lignicolous) habit. The
      phylogenetic position of this lignicolous fungus was compared with the
      lichenicolous species of Marchandiomyces and related species currently placed in
      the basidiomycetous families Corticiaceae and Ceratobasidiaceae using parsimony,
      likelihood, and Bayesian analyses of complete sequences of the nuclear small
      subunit and internal transcribed spacers ribosomal DNA, and a portion of the
      nuclear large subunit ribosomal DNA. These DNA sequences were obtained from
      isolated cultures of freshly collected specimens. Significant Bayesian posterior
      probabilities, as well as maximum likelihood and parsimony analyses, indicate
      that the new lignicolous species is closely related to M. corallinus, the type
      species of Marchandiomyces. In most analyses these two species are monophyletic
      with the lichenicolous M. aurantiacus, although this relationship is not strongly
      supported. Since M. lignicola is more closely related to M. corallinus than to M.
      aurantiacus, either a transition to the lignicolous habit occurred recently
      within an ancestral lichenicolous group or, more likely, transition to the
      lichenicolous habit arose recently and in parallel from an ancestral lignicolous
      habit.

PMID- 15736861
TI  - The genus Anthracoidea (Basidiomycota, Ustilaginales): a molecular phylogenetic
      approach using LSU rDNA sequences.
AB  - The phylogenetic relationship of 52 specimens representing 30 species of
      Anthracoidea (Ustilaginales) was investigated by molecular analyses using
      sequence data from the large subunit (LSU) of nuclear rDNA. Phylogenetic trees
      were inferred with neighbour-joining (NJ), maximum parsimony (MP), and Bayesian
      Markov chain Monte Carlo (MCMC) methods. The results are discussed with respect
      to the species concept and the subdivision of the genus into subgenera and
      sections. Collections from different hosts and localities were compared. Our
      analyses can neither support nor significantly reject the hypothesis of the
      bipartition of the genus Anthracoidea. Thus, the representatives of the subgenus
      Proceres appeared in the NJ analysis as a moderately supported monophylum,
      whereas MCMC analysis revealed a polyphyletic topology for this group. Paraphyly
      of the subgenus Anthracoidea was supported by all methods used. Sections
      Echinosporae and Leiosporae were each represented by two species in our analyses
      which grouped together with high support. Section Anthracoidea should be
      restricted to a highly supported group with extremely irregular to angular
      teliospore shape. However, these three sections do not cover the whole diversity
      of the subgenus Anthracoidea. Molecular data largely supported the traditional
      circumscription of species, and species delimitations are discussed.

PMID- 15736864
TI  - Genetic structure of the Pleurotus eryngii species-complex.
AB  - Assessment of genetic and phenotypic diversity is necessary to confidently
      distinguish genotypes of Pleurotus eryngii when seeking traits of interest and to
      identify strains with high yield potential. We studied 154 strains from Italy for
      quantitative (shape, size and yield), qualitative (colour, malformations and
      growing behaviour), and molecular (RAPD and minisatellite) traits. This
      population consisted of isolates mostly belonging to P. eryngii var. eryngii,
      var. ferulae or var. nebrodensis, from different regions of Italy. A replicated
      cultivation trial, with three blocks and three replicates for each strain within
      the block, was used as an experimental design to calculate trait estimates.
      Significant differences were observed between strains for basidiome number and
      weight, while no significant differentiation for quantitative morphological
      traits was observed between geographical origins and taxonomic groups.
      Qualitative morphological traits were efficient in differentiating isolates of P.
      eryngii var. nebrodensis. On average, yield per strain (basidiome weight) was
      correlated more with basidiome number than with size. The most stable yield
      traits were basidiome number and weight per strain. An average heritability of
      0.31 was estimated for yield related traits. A significant difference between
      var. ferulae and var. eryngii populations was detected for basidiome production
      measured as 'average harvest time'. Molecular markers showed a high level of
      heterogeneity within populations and a low, but significant, degree of
      differentiation among populations defined a priori. No population-specific marker
      was detected and the differential pattern of variation between vars. ferulae and
      eryngii was due to frequency-dependent alleles. The nebrodensis type was more
      differentiated from var. eryngii than from var. ferulae using either molecular or
      qualitative morphological traits.

PMID- 15736865
TI  - SSR-based detection of genetic variability in the charcoal root rot pathogen
      Macrophomina phaseolina.
AB  - Macrophomina phaseolina, the causal agent of charcoal root or collar rot, is an
      important plant pathogen especially in soybean and cotton. Single primers of
      simple sequence repeats (SSR) or microsatellite markers have been used for the
      characterization of genetic variability of different populations of M. phaseolina
      obtained from soybean and cotton grown in India and the USA. Genetic similarity
      between isolates was calculated, and cluster analysis was used to generate a
      dendrogram showing relationships between isolates collected from the two hosts.
      Forty isolates could be clustered into three major groups corresponding to their
      hosts and geographical region. The wide distribution of microsatellites in M.
      phaseolina genome was assessed by agarose gel electrophoresis of the PCR products
      generated by direct amplification of inter SSR regions DNA. This is the first
      report of the use of microsatellite markers to characterize the charcoal root rot
      pathogen. The SSR fingerprints (0.25-3.5 kb) generated using DNA from different
      populations of M. phaseolina of two hosts indicated that these repeats are
      interspersed within the genome of this pathogen. The variability found within
      closely related isolates of M. phaseolina indicated that such microsatellites are
      useful in population studies and represents a step towards identification of
      potential isolate diagnostic markers specific to soybean and cotton.

PMID- 15736866
TI  - Restriction mapping of the IGS region in Alternaria spp. reveals variable and
      conserved domains.
AB  - Accurate identification of Alternaria spp. is dependent upon the production of
      diagnostic morphological characters under defined cultural conditions and the
      proper assessment of character variation. This process is often compromised by
      variation in laboratory facilities and technical expertise. To assist taxon
      identification and phylogenetic studies, restriction site information from the
      intergenic spacer (IGS) region of nuclear rDNA was evaluated. Restriction maps
      were constructed from 15 species of Alternaria and Stemphylium botryosum
      (telemorph Pleospora herbarum) for 11 restriction enzymes using a new method for
      restriction mapping based on differential priming of IGS amplicons. IGS fragment
      size varied among species from 2.2-3.9 kb. Based upon restriction site homology
      among closely-related and more distantly related species, the IGS region could be
      divided into conserved and variable domains. The conserved domain was
      approximately 0.75 kb in size and was located at the 3' end of the IGS region.
      Restriction site homology within this region was very high, especially among
      closely related taxa. The remainder of the region comprised the variable domain,
      which encompassed considerable differences in size and restriction sites among
      taxa. The presence or absence of restriction sites among taxa was analyzed using
      methods of neighbor-joining. Phylogenetic relationships based on this method were
      concordant with those previously resolved based upon other methods and other
      genomic regions.

PMID- 15736867
TI  - Endophytism of Sclerotinia pseudotuberosa: PCR assay for specific detection in
      chestnut tissues.
AB  - The endophytic behaviour of Sclerotinia pseudotuberosa, cause of black rot of
      fruits of Castanea sativa, was investigated in asymptomatic tissues of the host,
      including nuts, buds and bark. A nested polymerase chain reaction (PCR) assay was
      developed for the specific detection of S. pseudotuberosa. Two specific primers,
      RAC1 and RAC2 were designed within the ITS1-5.8S-ITS2 region of rDNA by
      comparison of sequences of 24 isolates of S. pseudotuberosa and related species.
      Specificity of primers was tested against isolates of related and unrelated
      genera and the total DNA of C. sativa. The assay proved to be highly sensitive
      and capable of detecting picograms of S. pseudotuberosa DNA. Our study showed
      that S. pseudotuberosa was present asymptomatically in all the chestnut tissues
      tested. It is discussed that latency of S. pseudotuberosa in chestnut tissues may
      represent a adaptive strategy of the pathogen for rapid and massive host
      colonization in favourable environmental conditions.

PMID- 15736868
TI  - Direct analysis of ribosomal DNA in denaturing gradients: application on the
      effects of Phlebiopsis gigantea treatment on fungal communities of conifer
      stumps.
AB  - The aim of this study was to test the usefulness of direct PCR-amplification in
      analysing fungal diversity in stumps. The analysis was conducted on stumps
      treated against Heterobasidion spp. using a commercial formulation of Phlebiopsis
      gigantea (Rotstop), and carried out using denaturing gradient gel electrophoresis
      (DGGE) of small subunit (SSU) ribosomal DNA (rDNA) fragments PCR-amplified
      directly from wood DNA samples using two separate fungus-specific primer pairs.
      On average, two (range 0-9) different amplification products were observed by
      DGGE in single wood samples of approximately 500 mm3. The PCR products were
      classified into operational taxonomical unit (OTU) groups based on their DGGE
      mobility. Six OTUs could be affiliated with a known species based on a reference
      fungal collection of 37 species: Heterobasidion annosum, H. parviporum. Hypholoma
      capnoides, P. gigantea, Resinicium bicolor and Stereum sanguinolentum. Sequence
      analyses did not give further identifications. OTU profiles from old (6 yr-old)
      and fresh (1-year-old) Scots pine and Norway spruce stumps from treated and
      untreated forest plots were compared statistically, and some significant
      differences were observed in the species composition between the treated and
      untreated plots. However, the frequency of most of the OTUs did not seem to be
      affected, and the treatment did not seem to have reduced the overall level of
      fungal diversity. Based on these results, direct PCR-amplification seems to be
      useful in analyses of fungal communities in decaying conifer stumps.

PMID- 15736869
TI  - Screening of basidiomycetes and xylariaceous fungi for lignin peroxidase and
      laccase gene-specific sequences.
AB  - Lignin peroxidase and laccase gene-specific PCR primers were used to screen 38
      diverse basidiomycetes and xylariaceous fungi. Lignin peroxidase gene-specific
      sequences were obtained for basidiomycetes only and were highly divergent.
      Possession of laccase genes was relatively widespread among basidiomycetes, and
      is shown for the first time in Xylariaceae. All sequences were highly conserved
      with no variation resulting in changes to predicted amino acid sequence. Those
      basidiomycetes shown to possess lignin peroxidase and laccase genes also produced
      the enzyme in vitro. Conversely none of the xylariaceous fungi shown to possess
      laccase genes were able to do so, whilst others decolorized Poly R yet yielded no
      PCR amplicons.

PMID- 15736870
TI  - Towards a balanced social psychology: causes, consequences, and cures for the
      problem-seeking approach to social behavior and cognition.
AB  - Mainstream social psychology focuses on how people characteristically violate
      norms of action through social misbehaviors such as conformity with false
      majority judgments, destructive obedience, and failures to help those in need.
      Likewise, they are seen to violate norms of reasoning through cognitive errors
      such as misuse of social information, self-enhancement, and an over-readiness to
      attribute dispositional characteristics. The causes of this negative research
      emphasis include the apparent informativeness of norm violation, the status of
      good behavior and judgment as unconfirmable null hypotheses, and the allure of
      counter-intuitive findings. The shortcomings of this orientation include
      frequently erroneous imputations of error, findings of mutually contradictory
      errors, incoherent interpretations of error, an inability to explain the sources
      of behavioral or cognitive achievement, and the inhibition of generalized theory.
      Possible remedies include increased attention to the complete range of behavior
      and judgmental accomplishment, analytic reforms emphasizing effect sizes and
      Bayesian inference, and a theoretical paradigm able to account for both the
      sources of accomplishment and of error. A more balanced social psychology would
      yield not only a more positive view of human nature, but also an improved
      understanding of the bases of good behavior and accurate judgment, coherent
      explanations of occasional lapses, and theoretically grounded suggestions for
      improvement.

PMID- 15736871
TI  - The emulation theory of representation: motor control, imagery, and perception.
AB  - The emulation theory of representation is developed and explored as a framework
      that can revealingly synthesize a wide variety of representational functions of
      the brain. The framework is based on constructs from control theory (forward
      models) and signal processing (Kalman filters). The idea is that in addition to
      simply engaging with the body and environment, the brain constructs neural
      circuits that act as models of the body and environment. During overt
      sensorimotor engagement, these models are driven by efference copies in parallel
      with the body and environment, in order to provide expectations of the sensory
      feedback, and to enhance and process sensory information. These models can also
      be run off-line in order to produce imagery, estimate outcomes of different
      actions, and evaluate and develop motor plans. The framework is initially
      developed within the context of motor control, where it has been shown that inner
      models running in parallel with the body can reduce the effects of feedback delay
      problems. The same mechanisms can account for motor imagery as the off-line
      driving of the emulator via efference copies. The framework is extended to
      account for visual imagery as the off-line driving of an emulator of the motor
      visual loop. I also show how such systems can provide for amodal spatial imagery.
      Perception, including visual perception, results from such models being used to
      form expectations of, and to interpret, sensory input. I close by briefly
      outlining other cognitive functions that might also be synthesized within this
      framework, including reasoning, theory of mind phenomena, and language.

PMID- 15736873
TI  - Efficiency of an infiltration basin in removing contaminants from urban
      stormwater.
AB  - The efficiency of a Stormwater Infiltration Basin (SIB) to remove contaminants
      from urban stormwater was assessed in the current investigation. The SIB,
      installed in an urban suburb in eastern Sydney (Australia), was monitored over
      seven rainfall events to assess the removal efficiency of the remedial device for
      total suspended solids (TSS), nutrients (TP, TKN, N(ox), TN), trace metals (Cd,
      Cr, Cu, Fe, Mn, Ni, Pb, Zn), organochlorine pesticides and faecal coliforms (FC)
      from stormwater. The weighted average concentration (WAC) of TSS in the
      stormwater effluent from the SIB was reduced by an average of 50%, whereas the
      WAC of Cu, Pb and Zn were also reduced by an average 68%, 93% and 52%,
      respectively. However, the WAC of Cr, Fe, Mn and Ni displays either similar
      concentrations as the stormwater influent (Cr and Mn), or substantially higher
      concentrations (Fe and Ni), due possibly to leaching of fine-grained zeolite clay
      particles in the filtration bed. The mean removal efficiency of the SIB for total
      phosphorus (TP) and total Kjeldahl nitrogen (TKN) was 51% and 65%, respectively.
      In contrast, the average WAC of oxidisable nitrogen (nitrate and nitrite nitrogen
      or N(ox) is about 2.5 times greater in the effluent (1.34 +/- 0.69 mg L(-1)) than
      in the incoming stormwater (0.62 +/- 0.25 mg L(-1)). The WAC of total nitrogen
      (TN) was similar for stormwater at the in-flow and out-flow points. The SIB was
      very efficient in removing FC from stormwater; and the WAC of almost 70000 cfu
      (100 mL)(-1) at inflow was reduced to <2000 cfu (100 Ml)(-1) at the outflow,
      representing a mean removal efficiency of 96%. Due to the low concentrations of
      Cd, organochlorine pesticides and PAHs in the stormwater, it was not possible to
      assess the efficiency of the SIB in removing these contaminants.

PMID- 15736872
TI  - Movement behaviour of Medaka (Oryzias latipes) in response to sublethal
      treatments of diazinon and cholinesterase activity in semi-natural conditions.
AB  - Behavioural changes of medaka (Oryzias latipes) treated with an
      anticholinesterase insecticide, diazinon (0.1 mg L(-1)), were continuously
      observed for 4 days in semi-natural conditions. Although variations occurred in
      individual specimens, the movement tracks appeared differently with typical short
      range movement with irregular turns and shaking after the treatments. Eight
      movement patterns frequently observed before and after the treatments were
      selected, and the variables characterising the movement patterns were compared
      quantitatively. The variables were clearly differentiated when the movement
      patterns were correspondingly matched before and after the treatments (e.g.,
      vertical movements, horizontal movements, etc). Meander and stop duration were
      highly different among the selected movement patterns. Additionally, different
      degree of toxic response behaviours could also be detected by quantitative
      characterisation of the variables. Response behaviour was confirmed with
      toxicological experiments that show the decrease in the acetylcholine esterase
      activity in the head and body of specimens. Quantitative investigations on the
      variables of the movement tracks suggested the usefulness of response behaviour
      as a monitoring tool for environmental assessment.

PMID- 15736874
TI  - Biomonitoring of air pollution in a seasonally dry tropical suburban area using
      wheat transplants.
AB  - Air pollution has been identified as a serious problem throughout the world which
      causes tremendous loss to the crops by affecting plant growth and yield. Earlier,
      air pollution was restricted to urban and industrial regions. Over the last few
      decades, however, it has become evident that pollutants can be transported over
      long distances and hence their impact may be felt widely over rural areas. The
      present study was conducted to evaluate the impact of urban air pollution on
      suburban agriculture with respect to the changes in photosynthetic rate, stomatal
      conductance, water-use efficiency, plant height, numbers of tillers, leaves, ears
      and seeds, chlorophyll, carotenoid, protein, phenol, ascorbic acid, nitrogen and
      sulphate-sulphur contents and seed weight of pot-grown wheat plants (Triticum
      aestivum var. HUW 468) kept at different sites around Varanasi city receiving
      varying levels of pollution load. Mean concentrations of SO2, NO2 and O3 were
      monitored. The study clearly showed that plants are negatively affected by the
      ambient levels of air pollutants. Reduction in various parameters directly
      corresponded with the air pollution levels at different sites.

PMID- 15736875
TI  - Impacts of visitors on soil and vegetation of the recreational area "Nacimiento
      del Rio Mundo" (Castilla-La Mancha, Spain).
AB  - This study examines the effects of recreational use on the soil and vegetation at
      a site of ecological importance (Nacimiento del Rio Mundo, Albacete, Spain). The
      most visited sites showed increased soil compaction of approximately 50%, bare
      ground increase to 61 +/- 10% and a decrease in richness (from 25 +/- 2 to 15 +/-
      2 species), diversity (from 4.0 +/- 0.1 to 2.7 +/- 0.4) and stratification of
      plant species (from 80 +/- 11 to 21 +/- 4%). The most visited sites had 90% less
      plant species as compared to the least visited. Intense use was associated with
      the presence of nitrophilous plant and vegetal species with a morphology adapted
      to heavy trampling. The recreational areas showed a distribution pattern of
      impact radiating outwards from the most used and degraded point. At the most
      visited point, "Los Chorros" (the spring of the river), the impact radiated
      outwards for about 20 m. A pilot experiment examining the effects of one-year
      restriction to visitors for access to a formerly impacted area showed a plant
      cover increase by anthropic and not by native species of 57 percent units.

PMID- 15736876
TI  - Mapping tropical deforestation in Central Africa.
AB  - The NASA Landsat Pathfinder Humid Tropical Deforestation Project was to map
      deforestation activities in the humid tropics using datasets from both the
      Landsat TM (Thematic Mapper) and MSS (Multispectral Scanner System). In Central
      Africa, its effort had been constrained by the availability of cloud-free
      satellite coverage, especially for the 1970s Landsat MSS imagery. Here, we
      reported the deforestation rate and its spatial variability in the region using
      18 pairs of co-registered Landsat TM imagery from the 1980s to 1990s. Of the
      total classified area of 416,000 km2, there were approximately 217,000 km2 of
      dense forest and 24,000 km2 of degraded forest in the 1980s. A total of 1012 km2
      of forest, including 542 km2 of dense forest and 470 km2 of degraded forest, were
      cleared annually with an annual deforestation rate of 0.42%, varying among scenes
      ranging from 0.03 to 2.72%. Additionally, an average of 0.12% (ranging from 0.01
      to 0.77% among scenes) or 257 km2 of dense forest was degraded annually.
      Regression analyses indicated that extensive deforestation occurred in areas with
      larger forest cover, including dense and degraded forests. Image interpretation
      also confirmed the hypothesized relationship between deforestation and forest
      accessibility. The annual clearance of the dense forest was significantly related
      to the rural population density, and there was a positive relationship between
      the dense forest degraded during the 1980s-1990s and the degraded forest area in
      the 1980s.

PMID- 15736877
TI  - Relationship between basal soil respiration rate, tree stand and soil
      characteristics in boreal forests.
AB  - Soil respiration is considered to represent the overall microbial activity
      reflecting mineralisation of organic matter in soil. It is the most commonly used
      biological variable in soil studies. In long-term monitoring of forested areas,
      there is a need for reference values for soil microbiological variables in
      different forest ecosystems. In this study we describe the relationship between
      soil respiration rate, tree stand and humus chemical characteristics of boreal
      coniferous forests stands. Soil respiration rate was higher in pine dominated
      than in spruce dominated study sites when the result was calculated on dry matter
      bases. However, when calculated on area bases, the result was opposite and no
      difference was found when the soil respiration rate was calculated on organic
      carbon bases. Irrespective of the main tree species, the soil respiration rate
      was equal in different development classes but not equal in soil fertility
      classes, i.e. within forest site types based on differences in ground vegetation.
      Respiration rates were clearly higher in mesic sites when calculated on dry
      matter, C(org) or area bases. However, soil respiration rate did not correlate
      with soil chemical variables indicating site fertility. Soil respiration rate on
      dry matter basis was at a lower level in the south and on more fertile sites, and
      on the other hand at a higher level in older stands and on sites with a thicker
      organic layer.

PMID- 15736878
TI  - Development of arsenic testing field kit--a tool for rapid on-site screening of
      arsenic contaminated water sources.
AB  - Recognizing the enormity and severity of the problem of arsenic poisoning in
      ground water, the capabilities of commercially available arsenic detection field
      kits were critically evaluated. In the light of findings of the evaluation of
      these kits, their merits and limitations; a simple, efficient, prudent,
      userfriendly, indigenous field kit has been developed. The kit can be used for
      rapid on-site screening of arsenic contaminated water sources and is capable of
      detecting arsenic concentration as low as 0.01 mg L(-1), the guideline value for
      arsenic set by the WHO. The kit has been subjected to extensive laboratory and
      field testing. The details of development of the kit and its salient features are
      presented in the paper.

PMID- 15736879
TI  - Combustive approach for measuring total volatile phosphorus content in landfill
      gas.
AB  - A technique was developed to measure the total gaseous phosphorus content in
      biogas. The amount of air needed for a neutral to oxidising flame was mixed with
      the biogas. The gas mixture was burnt in a closed quartz burner and the
      combustion gasses were bubbled through a nitric acid solution. The phosphate
      content in the bubbling liquid was determined with sector field ICP-MS. The
      technique was validated in the lab with phosphine. Afterwards the set-up was
      installed on a landfill. The total gaseous phosphorus content in the landfill
      gas, measured with the combustive technique, ranged from 1.65 to 4.44 microg
      P/m3. At the same time the phosphine concentration in the landfill gas was
      determined gas chromatographically (GC). The phosphine (PH3) content measured
      with GC ranged from 7.6 to 16.7 microg PH3-P/m3. Since the phosphine-P content
      (GC) was consistently higher than the total gaseous phosphorus content
      (burner/ICP-MS), the hypothesised presence of highly toxic gaseous phosphorus
      compounds other than phosphine could not be demonstrated.

PMID- 15736880
TI  - Application of biological measures for stream integrity assessment in south-east
      Brazil.
AB  - The sensitivity of eleven metrics using macroinvertebrate assemblages were
      evaluated in an environmental gradient in a tropical river in south-east Brazil.
      Eight sites were sampled in an altitudinal range of 160-650 m.a.s.l. during 1999
      (April and August) and 2000 (February). Four substrates were sampled at each
      site: riffle litter, pool litter, stony substrates and sediment. Correspondence
      Analysis indicated that assemblages were primarily more influenced by physical
      changes (like deforestation and erosion processes) than the water chemistry. The
      sensitivity of each metric was evaluated through the application of box-and
      whisker plot method by its power to assess impairment (metrics should be able to
      discriminate reference sites from impaired sites) and natural variability
      (metrics should not discriminate two reference sites). Metrics that failed in at
      least one of the above premises were not considered as sensitive. In this study,
      the most sensitive metrics were Shannon index, BMWP-ASPT, %_EPT, and relative
      abundance of EPT to Chironomidae.

PMID- 15736881
TI  - Monitoring of spatial and temporal hydrochemical changes in groundwater under the
      contaminating effects of anthropogenic activities in Mersin region, Turkey.
AB  - The development of groundwater resources for water supply is a favored way in
      Turkey. The Berdan alluvial aquifer in Mersin is particularly productive, but
      little is known about the natural phenomena that govern the groundwater quality
      and the contamination sources in this region. During 2001 and 2002, water samples
      for chemical analysis were obtained from 27 wells and from two points of Berdan
      River and analyzed by ICP. Main chemical characteristics of sampled groundwater
      define two aquifers, which were also determined by hydrogeological
      investigations. The groundwater produced from some of the wells was affected by
      anthropogenic activities temporally and spatially by seawater intrusion. Berdan
      River is polluted with the wastewater discharges and river water also influences
      the groundwater quality.

PMID- 15736882
TI  - Spatial analysis and eutrophication assessment for chlorophyll a in Taihu Lake.
AB  - Spatial structure analysis and kriging analysis have been identified to be useful
      tools in illustrating the spatial patterns of variables. Taihu Lake is one of the
      largest fresh water lakes in China, and has suffered serious eutrophication in
      recent years due to the rapid economic development and growing environmental
      pollution in the Taihu Catchment. In this paper, spatial structural analysis,
      kriging interpolation and eutrophication assessment were carried out for
      chlorophyll a in the lake. Studies show that spherical model could be applied to
      fit all experimental variograms. Positive nuggets were observed for three
      directions except NE-SW direction. The variograms show some anisotropy with
      anisotropic ratio falling within 1.76. The spatial structural patterns of
      chlorophyll a in the lake were affected by factors such as distribution of
      pollution sources, water flow and wind. Two-dimensional ordinary block kriging
      was applied for interpolation process. An eutrophication assessment map was also
      made based on a water-quality evaluation standard. Results show that the content
      of chlorophyll a in Taihu Lake was quite high. The whole lake has suffered
      serious eutrophication. However, the eutrophic situation varied in space. Higher
      contents of chlorophyll a appeared mainly in the northern part of the lake.

PMID- 15736883
TI  - The effects of urban areas on benthic macroinvertebrates in two Colorado Plains
      rivers.
AB  - Water demands in arid and semi-arid areas, coupled with increased human
      populations and concomitant changes in land use, can greatly alter aquatic
      ecosystems. A good example of this type of system occurs along the eastern slope
      of the Colorado Rocky Mountains, U.S.A. Long-term macroinvertebrate metric data
      from the Big Thompson and Cache la Poudre Rivers, Colorado, were collected at one
      site above, and three sites in and downstream from urban areas. These data were
      compared both with regional reference and single reference sites in the
      respective rivers. Using the surrogate variables of potential urban impact
      (population and housing units), and the environmental gradient represented
      primarily by chemical factors, it was determined that there was an effect of
      urban land use that was reflected in the macroinvertebrate assemblages in both
      rivers. The most robust results were usually seen when regional reference data
      were used. However, even using only the upstream reference site in either river
      indicated some negative impacts from the urban areas. The long-term data,
      particularly in the Cache la Poudre River, showed that water quality has not been
      getting worse and there is some evidence of a slight improvement in downstream
      reaches, even with increased urban development.

PMID- 15736884
TI  - Relevant aspects of air quality in Oporto (Portugal): PM10 and O3.
AB  - The air quality Framework Directive (FWD) and the correspondent Daughter
      Directives defined the new strategy for air quality management in Europe. In
      general, the new standards are more restrictive than those established by the
      previous legislation. In Portugal, some difficulties can be previewed to achieve
      those new standards. Thus, this paper aims at evaluating the impact of
      application of the FWD to Oporto Metropolitan Area in what concerns to the most
      critical air pollutants in the area (PM10 and O3). The specific objectives were:
      (i) to analyse the concentration exceedances between 1999 and 2001; (ii) to
      identify the main emission sources; (iii) to evaluate the possibility of a new
      redistribution of the existing monitoring sites; (iv) to contribute to the
      definition of a new strategy for air quality management. The results showed that;
      (i) the standard values for PM10 and O3 were largely surpassed, possibly
      concluding that the FWD application implies a strong impact on the air quality
      management strategies; (ii) the main emission sources (road traffic and the
      neighbour stationary sources localised upwind) affect all the Metropolitan area
      through intra-region pollutant transport; (iii) it is safer maintaining the site
      localisation to avoid previewing exceedances through mathematical correlations;
      (iv) the reduction of PM10 and of ozone precursors must be performed considering
      new technologies for 'cleaner production' and gaseous depuration, a rigorous
      urban and territory planning, the creation of an efficient public transport
      network and the definition of strict measures for car maintenance.

PMID- 15736885
TI  - Statistical and geostatistical modelling of preliminarily adjusted defoliation on
      an European scale.
AB  - Since 1987 tree crown condition is surveyed annually in large parts of Europe
      mainly in terms of defoliation. The plot-wise means of defoliation from 1994 to
      2000 were evaluated by General Linear Models (GLM) in order to describe country
      specific levels of defoliation and age-trends. Additional runs with estimates for
      influences of insects and fungi were performed. The amount of variance of
      defoliation explained by country, age and its interaction was between 35% and 59%
      for the main tree species, except for Quercus ilex. Additionally, up to 10% could
      be explained by the inclusion of estimates for infestations by insects and fungi.
      Residuals of the GLMs were taken as a measure of forest condition not biased by
      country or age effects and interpreted as 'preliminarily adjusted defoliation'
      (PAD). PAD values were analysed using geostatistical methods. The modelled
      spatial autocorrelations were used for kriging. The resulting maps give an
      overview on regions with elevated defoliation, which may pinpoint regional causes
      of defoliation. The elimination of methodologically caused variance is a
      precondition of any cause-effect oriented analyses. The combination of
      explorative modelling and geostatistics will promote the choice of further
      promising predictors.

PMID- 15736886
TI  - Modeling nitrogen uptake and potential nitrate leaching under different
      irrigation programs in nitrogen-fertilized tomato using the computer program
      NLEAP.
AB  - Readily available nitrogen (N) sources such as ammonium nitrate with excessive
      irrigation present a potential hazard for the environment. The computer program
      Nitrate Leaching and Economic Analysis Package (NLEAP) is a mechanistic model
      developed for rapid site-specific estimates of nitrate-nitrogen (NO3-N) moving
      below the root zone in agricultural crops and potential impacts of NO3-N leaching
      into groundwater. In this study, the value of NLEAP was tested to simulate N
      uptake by crops and NO3-N leaching parameters in large lysimeters under the
      tomato crop. Three seedlings of tomato variety of H-2274 (Lycopersicum esculentum
      L.) were transplanted into each lysimeter. N fertilizer at the rate of 140 kg N
      ha(-1) was sidedressed in two split applications, the first half as ammonium
      sulphate and the second half as ammonium nitrate. The lysimeters were irrigated
      based on programs of C 0.75, 1.00, 1.25 and 1.50, C referring to class A-Pan
      evaporation coefficients. Parameters such as leaching index (LI), annual leaching
      risk potential (ALRP), N available for leaching (NAL), amount of NO3-N leached
      (NL) and amount of N taken up by the crops (NU) were estimated using the NLEAP
      computer model. To test the ability of model to simulate N uptake and NL,
      measured values were compared with simulated values. Significant correlations, R2
      = 0.92 and P < 0.03 for the first year and R2 = 0.86 and P < 0.06 for the second
      year, were found between measured and simulated values for crop N consumption,
      indicating that the NLEAP model adequately described crop N uptake under the
      varied irrigation programs using an optimal N fertilization program for the
      experimental site. Significant correlations, R2 = 0.96 and P < 0.01 for the first
      year and R2 = 0.97 and P < 0.01 for the second year, were also found between
      measured and simulated values of NL, indicating that the NLEAP model also
      adequately predicted NL under the varied irrigation programs. Therefore, this
      computer model can be useful to estimate the NO3-N moving beyond the root zone
      under conditions in which the present experiment was carried out. Also, the NLEAP
      estimated NAL values and other parameters can also be used to improve N
      management practices and N fertilizer recommendations that will help to decrease
      the adverse effect of N fertilizer on groundwater quality and farm profitability.

PMID- 15736887
TI  - Landscape development intensity index.
AB  - The condition of landscapes and the ecological communities within them is
      strongly related to levels of human activity. Human-dominated land uses and
      especially the intensity of the uses can affect adjacent ecological communities
      through direct, secondary, and cumulative impacts. Using land use data and a
      development-intensity measure derived from energy use per unit area, an index of
      Landscape Development Intensity (LDI) can be calculated for watersheds of varying
      sizes to estimate the potential impacts from human-dominated activities that are
      experienced by ecological systems within those watersheds. The intended use of
      the LDI is as an index of the human disturbance gradient (the level of human
      induced impacts on the biological, chemical, and physical processes of
      surrounding lands or waters). The LDI can be used at the scale of river, stream,
      or lake watersheds or at the smaller scale of individual isolated wetland
      watersheds. Based on land uses and land cover, the LDI can be applied using
      available GIS land use/land cover data, aerial photographs, or field surveys. A
      description of data needs and methods for calculating an LDI index and several
      applications of the index as a land use based ranking scheme of the human
      disturbance gradient for watersheds are given.

PMID- 15736888
TI  - Accumulation of heavy metals in kidney and heart tissues of Epinephelus microdon
      fish from the Arabian Gulf.
AB  - Levels of Pb, Co, Cu, Ni, Zn, Mn and Cd in the kidney and heart tissues of
      Epinephelus Microdon collected from the Arabian Gulf, Eastern province of Saudi
      Arabia, were determined by wet digestion-based atomic absorption method. The
      results indicated that accumulation pattern of analyzed metals in the kidney
      tissues followed the order; Zn > Cu > Pb > Ni > Co > Mn > Cd, with Zn at 47.73 +/
      13.26 ppm and Cd at 0.41 +/- 0.16 ppm. Cu, Mn, Co and Ni levels in the kidney
      tissues were significantly lower or within the ranges reported previously. In the
      heart tissue the analyzed metals followed almost the same pattern of metal
      accumulation; Zn > Cu > Pb > Co > Ni > Mn > Cd. The average lead (3.19 +/- 2.03
      ppm), nickel (1.69 +/- 0.52 ppm), cobalt (1.75 +/- 0.44 ppm), copper (3.96 +/-
      0.98 ppm) and cadmium (0.34 +/- 0.23 ppm) concentrations were found high in the
      heart tissues whereas zinc and manganese levels were found high in kidney
      tissues. In general, the data indicated that marine fish from the sampling site
      of Arabian Gulf are comparatively clean and unpolluted.

PMID- 15736889
TI  - Risk factors for periodontitis.
AB  - In recent years, it has become apparent that the pathogenesis of periodontal
      diseases is more complex than the presence of virulent microorganisms. In fact,
      it is now widely accepted that susceptibility to periodontitis varies greatly
      between individuals who harbor the same pathogenic microflora. To date, the bulk
      of evidence points to the host response to bacterial challenge as a major
      determinant of susceptibility. In this review, we will assess the data
      implicating various inherited and acquired risk factors for susceptibility to
      periodontal diseases.

PMID- 15736890
TI  - Combined effects of Nd:YAG laser irradiation with local antibiotic application
      into periodontal pockets.
AB  - The purpose of the present study was to assess the effects of Nd:YAG laser
      irradiation into periodontal pockets with or without the combination of local
      antibiotic application on clinical parameters and microbiological prevalence.
      Sixteen patients, each of whom had 4 or more sites with probing depth e x 4mm
      were included in this study. They were monitored clinically and microbiologically
      at baseline, 1 and 3 months after the treatment. Subgingival plaque samples were
      taken from periodontally involved sites with a probing depth of e x 4mm. A total
      of 135 sites were randomly assigned to the following treatments; Nd:YAG laser
      alone (Group L: 10 pps, 200 mJ for 90 sec, n = 37), local minocycline
      administration following laser treatment (Group LP, n = 33), povidone-iodine
      irrigation following laser treatment (Group LI, n = 33), and control group (Group
      C: sham procedure, n = 32). The prevalence of 18 subgingival taxa were determined
      using the checkerboard technique. The mean value of the pocket probing depth
      (PPD) significantly decreased in Group L, Group LP and Group LI, and the mean
      clinical attachment loss (CAL) decreased in all three treatment groups.
      Multivariate logistic regression analysis showed that Group LP showed the most
      improvement in PPD or CAL at 3 months. The proportions of Porphyromonas
      gingivalis, Tannerella forsythia (formerly Bacteroides forsythus) and Prevotella
      intermedia were significantly lower in Group LP than in Group L after 3 months.
      These results showed that Nd:YAG laser irradiation plus local minocycline
      provides a much greater reduction in PPD, CAL and the amount of
      periodontopathogenic bacteria than laser irradiation alone in periodontitis
      patients.

PMID- 15736891
TI  - Periodontal disease as part of the insulin resistance syndrome in diabetic
      patients.
AB  - Periodontal disease has been considered as a complication of diabetes mellitus. A
      recent epidemiological study revealed that obesity is an independent risk factor
      for periodontal disease. Obesity and type 2 diabetes mellitus are associated with
      many metabolic disorders including insulin resistance, dyslipidemia, hypertension
      and atherosclerosis. Chronic sub-clinical inflammation, although often for the
      most part in a healthy reference range, has recently been declared part of the
      insulin resistance syndrome, as such inflammatory responses appear to participate
      in the progression of metabolic disorders, including type 2 diabetes and
      atherosclerosis. We hypothesized that periodontal disease is one such sub
      clinical inflammation. Here, we summarize current knowledge supporting this
      concept primarily based on data obtained from our own studies and propose a new
      concept that periodontal disease should be considered as part of the insulin
      resistance syndrome.

PMID- 15736892
TI  - Diet and periodontitis.
AB  - The importance of diet in maintaining optimum body health is well recognized. An
      unhealthy diet has been implicated as a risk factor for several chronic diseases
      such as cardiovascular disease, hypertension, diabetes and certain cancers. The
      relationship between diet and periodontitis is not clear. The purpose of this
      article is to critically review the available literature and to shed new light on
      the impact of the overall diet on the prevalence and severity of chronic
      periodontitis in a given population.

PMID- 15736893
TI  - Reproducibility of clinical attachment level and probing depth of a manual probe
      and a computerized electronic probe.
AB  - The aim of this study was to evaluate the reproducibility of a conventional
      manual probe (MP) and an electronic probe, the Florida Probe (FP). Twenty
      patients with chronic periodontitis were assessed for pocket depth (PD) and
      clinical attachment level (CAL) by one examiner. Replicate measurements were
      taken one hour apart with each probe, on anterior teeth, at six sites per tooth.
      Pearson's correlation test and Student's paired t-test were used for the
      statistical analysis. The results showed that there were no significant
      differences in PD between the replicate measurements of both FP and MP (p >
      0.05), although the correlation value was higher for FP (r = 0.97, p < 0.01) than
      for MP (r = 0.54, p < 0.05). Considering CAL, no differences were found between
      replicate measurements for both FP and MP (p > 0.05) and correlation values were
      similar (0.57 and 0.64, respectively, p < 0.001). Although the FP showed higher
      correlation values for PD, no significant differences were found between
      duplicate measurements for both probes. Thus, both electronic and manual probing
      measurements seem to be reproducible when assessing periodontal disease.

PMID- 15736894
TI  - KSF: the impact on the profession.

PMID- 15736895
TI  - Abortions: are some happening too late?

PMID- 15736896
TI  - RCM stewards: making a real difference.

PMID- 15736897
TI  - Research into EPRs: how midwives really feel.
AB  - This article describes some of the findings of a two-year research project
      entitled The use of electronic patient records (EPRs) in maternity services:
      professional and public acceptability, commissioned by the Department of Health
      (DH). The main methods used were: --Literature review. --A national telephone
      survey of heads of midwifery (HOMs) in England (2001). --Case studies of
      maternity services in four NHS Trusts (2002). One of the findings of the research
      was that midwives and HOMs considered they had little knowledge of what EPRs are,
      and most were confused about whether their existing maternity information system
      (MIS) constituted an EPR system. The exact nature of EPRs was also contested
      among information technology (IT) professionals and NHS Trusts' EPR development
      strategies varied. Each Trust was, and still is, developing their own response to
      Information for health (NHS executive, 1998). Broadly speaking, these fell into
      one of two main categories of approach to EPR development. First, a 'best of
      breed' approach meant that departmental information systems, such as MISs were to
      be part of future EPR systems, and these specialist systems would become part of
      an inter-connected EPR system by being gradually connected with other
      departmental and Trust-wide information systems. Second, a 'big bang' or 'one
      system' approach meant all departmental systems were in the process of being
      replaced by a single supplier's system for the whole Trust, and specialist
      departments were expected to meet their information needs by using specialist
      modules within this system. The relative merits of each approach were hotly
      debated both locally and nationally during the course of the research project.
      Another finding was that midwives had little interest in EPRs, although the views
      expressed were contradictory. While midwives were not interested in being
      involved in EPR developments, they did want to see midwifery interests
      represented. Nearly all midwives and midwifery managers expected their
      perspective to be provided by the 'IT midwife'. The definition of this role
      varied in different services. Also, the research found that not all IT midwives
      were accepted by colleagues as appropriate representatives of their needs. At a
      time when there are increasing pressures on midwives to expand their role,
      (Department of Health, 1999: RCM, 2002b) we argue that midwives should play a
      more proactive role in the development of EPRs. The example is given of the claim
      that EPR systems save practitioners time (NHS executive, 1998). The research
      showed that maternity EPR systems consumed more time for midwives than they
      saved, although where midwives could see the clinical value of having the system
      this burden was considered more acceptable. Midwives should ask more questions
      about the value of the information systems they use and the new EPR systems that
      are being rolled out, and this needs to be encouraged by midwifery educators.

PMID- 15736898
TI  - Wearing purple.

PMID- 15736899
TI  - Understanding why women decline HIV testing.
AB  - BACKGROUND: The Department of Health (DH) set a target for HIV testing--uptake
      should be at least 90% by 31 December 2002 (Department of midwife Health, 2000),
      i the number of 80% decrease in n order to see a babies born with HIV (Tookey et
      al, 2002). As an exercise to measure Newham Healthcare Trust against this
      standard and review the antenatal care HIV-positive women received, the maternity
      unit undertook an audit. One in 160 pregnant women receiving antenatal care in
      the London Borough of Newham are HIV positive (Communicable Disease Screening
      Centre, 2003), according to the HIV anonymous screening programme, however the
      rate of transmission to the baby is virtually zero, when babies were followed up
      at birth, six months and one year Healthcare NH S Trust, 2003). Newham's HIV
      testing uptake ranges from 80% to 90% (with an average of 88%). A strategy for
      improving the uptake has been to explore why the 10% to 20% of women decline
      testing; hence the Trust underwent an audit to explore the reasons women gave
      when they declined testing. Audit findings Some 2138 forms were returned over a
      seven-month period, of which 328 (15%) were from women who declined HIV testing.
      Uptake within that period ranged from 74% to 90%. Ten new positive women were
      identified. The HIV-specialist midwife carries a caseload and is aware of all
      positive women, therefore was able to identify the new cases. The reasons given
      for decline ranged from cultural and religious beliefs to those who said they
      were not at risk. Practice implications Where women are aware of their HIV
      status, services can be put in place to support them through their pregnancy and
      life as a positive parent, equally important is the ability to minimise the risk
      of transmission to babies, therefore it is vital that women understand the
      purpose of early diagnosis through testing and its consequences. Midwives have a
      vital role to play in ensuring pregnant women receive adequate information to
      form their decision. If a woman chooses not to have the test, midwives should
      explore her reasons without prejudice. It is also recommended that women who
      decline testing are reoffered the HIV test at their subsequent antenatal visit,
      allowing them the opportunity to digest the information and discuss it with a
      partner. The purpose of the audit was to assess how the Trust would meet the DH
      target (90% uptake), as part of a review of the maternity HIV service.

PMID- 15736900
TI  - Continuing innovation.

PMID- 15736901
TI  - Information technology in the NHS: the effect on midwifery.

PMID- 15736902
TI  - Heads above the parapet: consultant midwifery reviewed.

PMID- 15736903
TI  - Traumatic birth.

PMID- 15736904
TI  - Help wanted: umbilical cord pH research.

PMID- 15736905
TI  - Care for teenage mothers.

PMID- 15736906
TI  - Child-friendly working hours.

PMID- 15736907
TI  - Where is midwifery going?

PMID- 15736908
TI  - Attitudes to breech birth.

PMID- 15736909
TI  - Returning to practice.

PMID- 15736911
TI  - Effects of dietary n-3 polyunsaturated fatty acids on T-cell membrane composition
      and function.
AB  - Dietary n-3 PUFA have been shown to attenuate T-cell-mediated inflammation, in
      part, by suppressing T-cell activation and proliferation. n-3 PUFA have also been
      shown to promote apoptosis, another important mechanism for the prevention of
      chronic inflammation by maintaining T-cell homeostasis through the contraction of
      populations of activated T cells. Recent studies have specifically examined Fas
      death receptor-mediated activation-induced cell death (AICD), since it is the
      form of apoptosis associated with peripheral T-cell deletion involved in
      immunological tolerance and T-cell homeostasis. Data from our laboratory indicate
      that n-3 PUFA promote AICD in T helper 1 polarized cells, which are the mediators
      of chronic inflammation. Since Fas and components of the death-inducing signaling
      complex are recruited to plasma membrane microdomains (rafts), the effect of
      dietary n-3 PUFA on raft composition and resident protein localization has been
      the focus of recent investigations. Indeed, there is now compelling evidence that
      dietary n-3 PUFA are capable of modifying the composition of T-cell membrane
      microdomains (rafts). Because the lipids found in membrane microdomains actively
      participate in signal transduction pathways, these results support the hypothesis
      that dietary n-3 PUFA influence signaling complexes and modulate T-cell
      cytokinetics in vivo by altering T-cell raft composition.

PMID- 15736910
TI  - n-3 fatty acids, inflammation, and immunity--relevance to postsurgical and
      critically ill patients.
AB  - Excessive or inappropriate inflammation and immunosuppression are components of
      the response to surgery, trauma, injury, and infection in some individuals and
      these can lead, progressively, to sepsis and septic shock. The hyperinflammation
      is characterized by the production of inflammatory cytokines, arachidonic acid
      derived eicosanoids, and other inflammatory mediators, while the
      immunosuppression is characterized by impairment of antigen presentation and of T
      helper cell type-1 responses. Long-chain n-3 FA from fish oil decrease the
      production of inflammatory cytokines and eicosanoids. They act both directly (by
      replacing arachidonic acid as an eicosanoid substrate and by inhibiting
      arachidonic acid metabolism) and indirectly (by altering the expression of
      inflammatory genes through effects on transcription factor activation). Thus,
      long-chain n-3 FA are potentially useful anti-inflammatory agents and may be of
      benefit in patients at risk of developing sepsis. As such, an emerging
      application of n-3 FA is in surgical or critically ill patients where they may be
      added to parenteral or enteral formulas. Parenteral or enteral nutrition
      including n-3 FA appears to preserve immune function better than standard
      formulas and appears to partly prevent some aspects of the inflammatory response.
      Studies to date are suggestive of clinical benefits from these approaches,
      especially in postsurgical patients.

PMID- 15736912
TI  - Immunomodulation by polyunsaturated fatty acids: impact on T-cell signaling.
AB  - In recent years the potential application of the immunomodulatory effects of
      polyunsaturated FA (PUFA), particularly those of the n-3 series, in a variety of
      inflammatory disorders has been of considerable interest. However, the mechanisms
      underlying inhibition of T-cell activation have so far been unclear. In this
      short review we summarize possible mechanisms for the modulation of immune
      responses by PUFA. Effects of PUFA on T-cell signal transduction pathways and
      underlying molecular mechanisms are described in detail. These recent results add
      considerably to the understanding of mechanisms of PUFA actions, but their
      relevance in the in vivo situation must still be elucidated.

PMID- 15736913
TI  - Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing
      cellularity of adipose tissue.
AB  - Omega-3 PUFA of marine origin reduce adiposity in animals fed a high-fat diet.
      Our aim was to learn whether EPA and DHA could limit development of obesity and
      reduce cellularity of adipose tissue and whether other dietary FA could influence
      the effect of EPA/DHA. Weight gain induced by composite high-fat diet in C57BL/6J
      mice was limited when the content of EPA/DHA was increased from 1 to 12% (wt/wt)
      of dietary lipids. Accumulation of adipose tissue was reduced, especially of the
      epididymal fat. Low ratio of EPA to DHA promoted the effect. A higher dose of
      EPA/DHA was required to reduce adiposity when admixed to diets that did not
      promote obesity, the semisynthetic high-fat diets rich in EFA, either alpha
      linolenic acid (ALA, 18:3 n-3, the precursor of EPA and DHA) or linoleic (18:2 n
      6) acid. Quantification of adipose tissue DNA revealed that except for the diet
      rich in ALA the reduction of epididymal fat was associated with 34-50% depression
      of tissue cellularity, similar to the 30% caloric restriction in the case of the
      high-fat composite diet. Changes in plasma markers and adipose gene expression
      indicated improvement of lipid and glucose metabolism due to EPA/DHA even in the
      context of the diet rich in ALA. Our results document augmentation of the
      antiadipogenic effect of EPA/DHA during development of obesity and suggest that
      EPA/DHA could reduce accumulation of body fat by limiting both hypertrophy and
      hyperplasia of fat cells. Increased dietary intake of EPA/DHA may be beneficial
      regardless of the ALA intake.

PMID- 15736914
TI  - Effect of cancer cachexia on triacylglycerol/fatty acid substrate cycling in
      white adipose tissue.
AB  - The effect of cancer cachexia on the TAG/FA substrate cycle in white adipose
      tissue was determined in vivo using the MAC16 murine model of cachexia. When
      compared with non-tumor-bearing animals, the rate of TAG-glycerol production was
      found to be increased almost threefold in animals bearing the MAC13 tumor, which
      does not induce cachexia, but was not further elevated in animals bearing the
      MAC16 tumor. In both cases TAG-glycerol production and de novo synthesis of TAG
      FA were also increased above non-tumor-bearing animals. In animals bearing the
      MAC16 tumor, the TAG-FA rates were significantly higher than in animals bearing
      the MAC13 tumor. This suggests that the presence of the tumor alone is sufficient
      to cause an increase in cycling rate, and in the absence of an elevated energy
      intake (MAC16) this may contribute to the depletion of adipose tissue.

PMID- 15736915
TI  - A randomized controlled trial of the effect of fish oil supplementation in late
      pregnancy and early lactation on the n-3 fatty acid content in human breast milk.
AB  - The aim of this research was to investigate the effect of fish oil
      supplementation, in the third trimester of pregnancy and early lactation period
      of healthy pregnant Danish women. Forty-four pregnant women were randomly
      allocated to fish oil supplementation (1.3 g EPA and 0.9 g DHA per day) from week
      30 of gestation (FO-group) or to a control regimen (olive oil or no oil;
      controls). The FO-group was randomly subdivided into women stopping fish oil
      supplementation at delivery IFO(pregn)], and women continuing supplementation for
      an additional 30 d [FO(pregn/lact)]. Thirty-six women agreed to collect milk
      samples at days 4, 16, and 30 postpartum. The FA composition of the milk samples
      was determined by GLC. At days 4, 16, and 30 in lactation, FO(pregn/lact) women
      (n = 12) had, respectively 2.3 (P = 0.001), 4.1 (P = 0.001), and 3.3 (P = 0.001)
      times higher mean contents of LCPUFA(n-3) in their breast milk compared with
      controls (n = 13), and 1.7 (P = 0.005), 2.8 (P = 0.001), and 2.8 (P = 0.001)
      times higher LCPUFA(n-3) contents, respectively, at these days compared with
      FO(pregn) women (n = 11). The latter group did not differ significantly from
      controls with regard to LCPUFA(n-3) content in the breast milk. Similar results
      were obtained when analyzing separately for effects on the milk content of DHA.
      Dietary supplementation with 2.7 g LCPUFA(n-3) per day from week 30 of gestation
      and onward more than tripled the LCPUFA(n-3) content in early breast milk;
      supplementation limited to pregnancy only was much less effective.

PMID- 15736916
TI  - Modifying milk fat composition of dairy cows to enhance fatty acids beneficial to
      human health.
AB  - There is increased consumer awareness that foods contain microcomponents that may
      have beneficial effects on health maintenance and disease prevention. In milk fat
      these functional food components include EPA, DHA, and CLA. The opportunity to
      enhance the content of these FA in milk has improved as a result of recent
      advances that have better defined the interrelationships between rumen
      fermentation, lipid metabolism, and milk fat synthesis. Dietary lipids undergo
      extensive hydrolysis and biohydrogenation in the rumen. Milk fat is predominantly
      TG, and de novo FA synthesis and the uptake of circulating FA contribute nearly
      equal amounts (molar basis) to the FA in milk fat. Transfer of dietary EPA and
      DHA to milk fat is very low (<4%); this is, to a large extent, related to their
      extensive biohydrogenation in the rumen, and also partly due to the fact that
      they are not transported in the plasma lipid fractions that serve as major
      mammary sources of FA uptake (TG and nonesterified FA). Milk contains over 20
      isomers of CLA but the predominant one is cis-9,trans-11 (75-90% of total CLA).
      Biomedical studies with animal models have shown that this isomer has
      anticarcinogenic and anti-atherogenic activities. cis-9,trans-11-CLA is produced
      as an intermediate in the rumen biohydrogenation of linoleic acid but not of
      linolenic acid. However, it is only a transient intermediate, and the major
      source of milk fat CLA is from endogenous synthesis. Vaccenic acid, produced as a
      rumen biohydrogenation intermediate from both linoleic acid and linolenic acid,
      is the substrate, and delta9-desaturase in the mammary gland and other tissues
      catalyzes the reaction. Diet can markedly affect milk fat CLA content, and there
      are also substantial differences among individual cows. Thus, strategies to
      enhance milk fat CLA involve increasing rumen outflow of vaccenic acid and
      increasing delta9-desaturase activity, and through these, several-fold increases
      in the content of CLA in milk fat can be routinely achieved. Overall,
      concentrations of CLA, and to a lesser extent EPA and DHA, can be significantly
      enhanced through the use of diet formulation and nutritional management of dairy
      cows.

PMID- 15736917
TI  - Increasing homicide rates and linoleic acid consumption among five Western
      countries, 1961-2000.
AB  - Clinical intervention trials and animal studies indicate that increasing dietary
      intakes of long chain n-3 FA or reducing linoleic acid intake may reduce
      aggressive and violent behaviors. Here we examine if economic measures of greater
      n-6 consumption across time and countries correlate with greater risk of
      homicide. Linoleic acid available for human consumption was calculated from World
      Health Organization disappearance data for 12 major seed oils in the food supply
      for the years 1961 to 2000 in Argentina, Australia, Canada, the United Kingdom,
      and the United States (US). Homicide mortality rates, adjusted for age, were
      obtained from the central judicial authority of each country. Apparent linoleic
      acid intake from seed oil sources ranged from 0.29 en% (percentage of daily food
      energy) (Australia 1962) to 8.3 en% (US 1990s). Greater apparent consumption of
      linoleic acid correlated with higher rates of homicide mortality over a 20-fold
      range (0.51-10.2/100,000) across countries and time in an exponential growth
      regression model (r = 0.94, F = 567, P < 0.00001). Within each country,
      correlations between greater linoleic acid disappearance and homicide mortality
      over time were significant in linear regression models. Randomized controlled
      trials are needed to determine if reducing high intakes of linoleic acid by seed
      oils with alternative compositions can reduce the risk of violent behaviors.
      These dietary interventions merit exploration as relatively cost-effective
      measures for reducing the pandemic of violence in Western societies, just as
      dietary interventions are reducing cardiovascular mortality. Low linoleate diets
      may prevent behavioral maladies that correctional institutions, social service
      programs, and mental health providers intend to treat.

PMID- 15736918
TI  - Long-chain polyunsaturated fatty acids in childhood developmental and psychiatric
      disorders.
AB  - Both omega-3 and omega-6 long-chain PUFA (LC-PUFA) are crucial to brain
      development and function, but omega-3 LC-PUFA in particular are often lacking in
      modern diets in developed countries. Increasing evidence, reviewed here,
      indicates that LC-PUFA deficiencies or imbalances are associated with childhood
      developmental and psychiatric disorders including ADHD, dyslexia, dyspraxia, and
      autistic spectrum disorders. These conditions show a high clinical overlap and
      run in the same families, as well as showing associations with various adult
      psychiatric disorders in which FA abnormalities are already implicated, such as
      depression, other mood disorders, and schizophrenia. Preliminary evidence from
      controlled trials also suggests that dietary supplementation with LC-PUFA might
      help in the management of these kinds of childhood behavioral and learning
      difficulties. Treatment with omega-3 FA appears most promising, but the few small
      studies published to date have involved different populations, study designs,
      treatments, and outcome measures. Large-scale studies are now needed to confirm
      the benefits reported. Further research is also required to assess the durability
      of such treatment effects, to determine optimal treatment compositions and
      dosages, and to develop reliable ways of identifying those individuals most
      likely to benefit from this kind of treatment. Childhood developmental and
      psychiatric disorders clearly reflect multifactorial influences, but the study of
      LC-PUFA and their metabolism could offer important new approaches to their early
      identification and management. Heterogeneity and comorbidity are such, however,
      that a focus on specific traits or symptoms may prove more fruitful than an
      exclusive reliance on current diagnostic categories.

PMID- 15736920
TI  - Olive oil consumption and reduced incidence of hypertension: the SUN study.
AB  - Olive oil, a major component of the Mediterranean diet, has been associated in
      some small clinical trials and cross-sectional studies with a reduction in blood
      pressure. The objective of this study was to assess the association of olive oil
      consumption with the incidence of hypertension in an epidemiologic cohort, the
      Seguimiento Universidad de Navarra (SUN) study. The SUN Project is a prospective
      cohort study whose members are all university graduates. The recruitment and
      follow-up of participants is made using mailed questionnaires. Diet was assessed
      using a semiquantitative food frequency questionnaire previously validated in
      Spain, with 136 items. Outcomes of interest were newly diagnosed cases of
      hypertension, as reported by participants in the follow-up questionnaires.
      Logistic regression models were fit to assess the risk of hypertension associated
      with olive oil consumption. For the present analysis, we have taken in
      consideration the first 6,863 participants, with at least 2 yr of follow-up.
      After a median follow-up time of 28.5 mon, the cumulative incidence of
      hypertension was 4.7% in men and 1.7% in women. A lower risk of hypertension was
      observed among participants with a higher olive oil consumption at baseline, but
      the results were not statistically significant (P = 0.13 for the linear trend
      test in the multivariate model). However, among men, the adjusted odds ratios
      (OR) (95% confidence intervals) of hypertension for the second to fifth quintiles
      of olive oil consumption, compared with the first quintile, were 0.55 (0.28
      1.10), 0.75 (0.39-1.43), 0.32 (0.15-0.70), and 0.46 (0.23-0.94), respectively (P
      = 0.02 for linear trend). No association was found between olive oil consumption
      and the risk of hypertension among women. In conclusion, in a Mediterranean
      population, we found olive oil consumption to be associated with a reduced risk
      of hypertension only among men. The lack of association observed among women
      might be attributed to the overall lower incidence of hypertension found among
      females and the resulting lower statistical power.

PMID- 15736919
TI  - Olive oil and modulation of cell signaling in disease prevention.
AB  - Epidemiological studies show that populations consuming a predominantly plant
      based Mediterranean-style diet exhibit lower incidences of chronic diseases than
      those eating a northern European or North American diet. This observation has
      been attributed to the greater consumption of fruits and vegetables and the lower
      consumption of animal products, particularly fat. Although total fat intake in
      Mediterranean populations can be higher than in other regions (ca. 40% of
      calories), the greater proportion is derived from olive oil and not animals.
      Increased olive oil consumption is implicated in a reduction in cardiovascular
      disease, rheumatoid arthritis, and, to a lesser extent, a variety of cancers.
      Olive oil intake also has been shown to modulate immune function, particularly
      the inflammatory processes associated with the immune system. Olive oil is a
      nonoxidative dietary component, and the attenuation of the inflammatory process
      it elicits could explain its beneficial effects on disease risk since oxidative
      and inflammatory stresses appear to be underlying factors in the etiology of
      these diseases in man. The antioxidant effects of olive oil are probably due to a
      combination of its high oleic acid content (low oxidation potential compared with
      linoleic acid) and its content of a variety of plant antioxidants, particularly
      oleuropein, hydroxytyrosol, and tyrosol. It is also possible that the high oleic
      acid content and a proportionate reduction in linoleic acid intake would allow a
      greater conversion of alpha-linolenic acid (18:3n-3) to longer-chain n-3 PUFA,
      which have characteristic health benefits. Adoption of a Mediterranean diet could
      confer health benefits in high-risk populations.

PMID- 15736922
TI  - Investigations on the reaction pattern of photosystem II in leaves from
      Arabidopsis thaliana by time-resolved fluorometric analysis.
AB  - The transients of normalized fluorescence yield induced by an actinic laser flash
      in dark adapted leaves of Arabidopsis thaliana plants were measured with new
      equipment, that was developed as part of this work and permits the covarage of a
      wide time domain of 8 decades from 100 ns to 10 s. The raw data obtained were
      processed and analyzed within the framework of the "3-quencher" model with Q(A)
      as photochemical and P680(+)(*) and (3)Car as nonphotochemical quenchers.
      Comparative measurements with hydroxylamine treated PS II membrane fragments from
      spinach revealed that the widely used "dogma"of virtually identical efficiency of
      photochemical (Q(A)) and nonphotochemical (P680(+)(*)) quenching has to be
      revised: the constant of the latter exceeds that of the former by a factor of
      about 2. As a consequence, the probability of recombination between P680(+)(*)
      and Q(A)(-) and its kinetics have to be explicitly taken into account for the
      interpretation of flash induced fluorescence yield transients. The analysis of
      the experimental data within this extended "3-quencher" model reveals that a
      fully consistent description is achieved for the data gathered from measurements
      with intact leaves from wild type plants excited with actinic laser flashes of
      different energies (number of photons per flash and unit area). On the basis of
      these results it is shown that, in dark adapted leaves excited with a single
      laser flash, P680(+)(*) is predominantly (about 80% of the total reaction)
      reduced by Y(Z) via nanosecond kinetics and Q(A)(-) reoxidation is dominated by a
      kinetics of about 150 mus that are ascribed to PS II complexes with the Q(B) site
      occupied by PQ. The excess of excited chlorophyll singlet states decays to a
      significant extent via the carotenoid "triplet valve"with transient population of
      (3)Car. The present data provide the basis for analyses of A. thaliana mutants
      with modified lipid content and composition. The results of these investigations
      are described in an accompanying report (Steffen, R., Kelly, A. A., Huyer, J.,
      Dormann, P., and Renger, G. (2005) Investigations on the reaction pattern of
      photosystem II in leaves from Arabidopsis thaliana wild type plants and mutants
      with genetically modified lipid content, Biochemistry 44, 3134-3142).

PMID- 15736923
TI  - Investigations on the reaction pattern of photosystem II in leaves from
      Arabidopsis thaliana wild type plants and mutants with genetically modified lipid
      content.
AB  - The role of digalactosyldiacylglycerol (DGDG) for the functional competence of
      photosystem II (PS II) has been analyzed in leaves of Arabidopsis thaliana plants
      where the lipid composition was selectively modified by genetic mutations.
      Measurements with a newly developed laser flash fluorometer and data evaluation
      within the framework of an extended "3-quencher" model lead to the following
      results: (i) the normalized fluorescence transients F(t)/F(0) induced by an
      actinic laser flash in dark adapted leaves are virtually the same in wild type
      (WT) and mutants with diminished (about 50%) monogalactosyldiacylglycerol (MGDG)
      content (mgd1 mutant); (ii) significant changes of the F(t)/F(0) curves are
      observed in mutants with a severely reduced DGDG content; (iii) in mutants dgd1
      and dgd1 dgd2-1 with DGDG contents of 1/15 of the control and below the detection
      limit, respectively, the probability of the dissipative recombination reaction
      between P680(+)(*) and Q(A)(-) increases by factors of about two and four,
      respectively; (iv) the acceptor side reactions are only slightly affected; (v)
      excitation with actinic laser flash energies above the saturation level of
      photosynthesis gives rise to elevated carotenoid triplet formation in mutants
      dgd1 and dgd1 dgd2-1; and (vi) the relationship between DGDG content and
      functional effect(s) on PS II is strikingly nonlinear. A small fraction of DGDG
      molecules of the total pool is inferred to be specifically bound to PS II as an
      essential constituent for its functional competence.

PMID- 15736921
TI  - Hypochlorous acid scavenging properties of local Mediterranean plant foods.
AB  - Oxidative modification of low density lipoprotein (LDL) is involved in the
      pathogenesis of atherosclerosis and coronary heart disease, which are low in the
      Mediterranean area possibly due to a high dietary proportion of plant foods.
      Ethanolic extracts were prepared from more than 120 Mediterranean edible plants
      collected in remote areas (which maintain their traditional diet) and their
      antioxidant potential was studied. Extracts derived from Agaricus campestris,
      Cynara cardunculus, Thymus pulegioides, and Vicia faba were subjected to further
      analysis in this study. The extracts' potential to scavenge the DPPH radical (2,2
      diphenyl-1-picrylhydrazyl radical) and hypochlorous acid (HOCl), as well as their
      antioxidant capacity, was comparable to the those obtained for standard
      antioxidants (e.g., quercetin, Trolox). Myeloperoxidase (MPO) catalyzes the
      production of the highly chlorinating and oxidizing agent HOCl, which reacts with
      the LDL apoprotein moiety, leading to the derivatization of its aminoacidic
      residues. Coincubation with extracts significantly prevented HOCl-induced
      modification of the LDL residue tryptophan, whereas higher concentrations were
      required to retard lysine damage. Moreover, the extracts inhibited MPO-catalyzed
      guaiacol oxidation in a concentration-dependent manner in a cell-free assay but,
      in contrast, did not affect MPO activity in isolated human neutrophils. MPO is
      also known to facilitate nitric dioxide oxidation. The formation of 3
      nitrotyrosine was significantly lower in bovine endothelial aortic cells
      incubated with C. cardunculus or T. pulegioides. In synthesis, our study shows
      that local Mediterranean plant foods prevent HOCl toxicity in vitro and, thus,
      suggests further mechanisms responsible for the reported health-beneficial effect
      of the Mediterranean diet.

PMID- 15736924
TI  - Cysteine-to-serine mutants of the human copper chaperone for superoxide dismutase
      reveal a copper cluster at a domain III dimer interface.
AB  - Cysteine-to-serine mutants of a maltose binding protein fusion with the human
      copper chaperone for superoxide dismutase (hCCS) were studied with respect to (i)
      their ability to transfer Cu to E,Zn superoxide dismutase (SOD) and (ii) their Zn
      and Cu binding and X-ray absorption spectroscopic (XAS) properties. Previous work
      has established that Cu(I) binds to four cysteine residues, two of which, C22 and
      C25, reside within an Atox1-like N-terminal domain (DI) and two of which, C244
      and C246, reside in a short unstructured polypeptide chain at the C-terminus
      (DIII). The wild-type (WT) protein shows an extended X-ray absorption fine
      structure (EXAFS) spectrum characteristic of cluster formation, but it is not
      known how such a cluster is formed. Cys to Ser mutagenesis was used to
      investigate the Cu binding in more detail. Single Cys to Ser mutations, as
      represented by C22S and C244S, did little to affect the metal binding ratios of
      hCCS. Both mutants still showed approximately 2 Cu(I) ions and 1 Zn ion per
      protein. The double mutants C22/24S and C244/246S, on the other hand, showed Cu
      binding stoichiometries close to 1:1. The Zn-EXAFS of WT CCS showed a 3-4
      histidine ligand environment that is consistent with Zn binding in the SOD-like
      domain II of CCS. The Zn environment remained unchanged between wild type and all
      of the mutant CCS proteins. Single Cys to Ser mutations displayed lower activity
      than WT protein, although close to full activity could be rescued by increasing
      the CCS:SOD ratios to 8:1 in the assay mixture. The structure of the Cu centers
      of the single mutants as revealed by EXAFS was also similar to that of WT
      protein, with clear indications of a Cu cluster. On the other hand, the double
      mutants showed a greater degree of perturbation. The DI C22/25S mutant was 70%
      active and formed a cluster with a more intense Cu-Cu interaction. The DIII
      C244/246S mutant retained only a fraction (16%) of activity and did not form a
      cluster. The results suggest the formation of a DIII-DIII cluster within a
      dimeric or tetrameric protein and further suggest that this cluster may be an
      important element of the copper transfer machinery.

PMID- 15736925
TI  - Characterization of a succinyl-CoA radical-cob(II)alamin spin triplet
      intermediate in the reaction catalyzed by adenosylcobalamin-dependent
      methylmalonyl-CoA mutase.
AB  - The electron paramagnetic resonance (EPR) spectrum of an intermediate freeze
      trapped during the steady state of the reaction catalyzed by the
      adenosylcobalamin (AdoCbl)-dependent enzyme, methylmalonyl-CoA mutase, has been
      studied. The EPR spectrum is that of a hybrid triplet spin system created as a
      result of strong electron-electron spin coupling between an organic radical and
      the low-spin Co(2+) in cob(II)alamin. The spectrum was analyzed by simulation to
      obtain the zero-field splitting (ZFS) parameters and Euler angles relating the
      radical-to-cobalt interspin vector to the g axis system of the low-spin Co(2+).
      Labeling of the substrate with (13)C and (2)H was used to probe the identity of
      the organic radical partner in the triplet spin system. The patterns of
      inhomogeneous broadening in the EPR signals produced by [2'-(13)C]methylmalonyl
      CoA and [2-(13)C]methylmalonyl-CoA as well as line narrowing resulting from
      deuterium substitution in the substrate were consistent with those expected for a
      succinyl-CoA radical wherein the unpaired electron was centered on the carbon
      alpha to the free carboxyate group of the rearranged radical. The interspin
      distance and the Euler angles were used to position this product radical into the
      active site of the enzyme.

PMID- 15736926
TI  - Zn7metallothionein-3 and the synaptic vesicle cycle: interaction of
      metallothionein-3 with the small GTPase Rab3A.
AB  - In the central nervous system, a large amount of chelatable Zn(2+) is sequestered
      in presynaptic vesicles of certain glutamatergic nerve terminals. The exo
      endocytotic cycle of synaptic vesicles is strictly linked to the small GTPase
      Rab3A. Metallothionein-3 (Zn(7)MT-3) has been proposed to be involved in the
      intracellular trafficking of Zn(2+) in zinc-containing neurons, but its role in
      this process is not understood. By using affinity precipitation and surface
      plasmon resonance analysis, we show that Zn(7)MT-3 binds reversibly to Rab3A.GDP
      (K(D) = 2.6 microM), but not to Rab3A.GTP. The binding of Zn(7)MT-3 to Rab3A.GDP
      is specific as no binding was observed with the metal-free form of MT-3.
      Mutational studies of Rab3A mapped the interaction site to the effector binding
      site of the protein. This location is further supported by the kinetics of GDP
      exchange, which was found to be unaffected by binding of Zn(7)MT-3 to Rab3A.GDP.
      The interaction of Zn(7)MT-3 with Rab3A indicates that Zn(7)MT-3 is not merely a
      cellular Zn(2+) buffer, but actively participates in synaptic vesicle trafficking
      upstream of vesicle fusion.

PMID- 15736927
TI  - Structure and dynamics of the actin filament.
AB  - The structures of filamentous Mg-ATP-actin (F actin) in the presence and absence
      of KCl have been mapped with hydroxyl radicals (*OH) generated by synchrotron X
      ray radiolysis. Proteolysis and mass spectrometry (MS) analysis revealed 52
      reactive side-chain sites from 27 distinct peptides within actin. The
      reactivities of these probe sites with *OH in the F-actin states are compared
      with those of Mg-ATP-G-actin (monomers) analyzed previously [Guan, J.-Q. et al.
      (2003) Biochemistry 42, 11992-12000]. Filament-dependent protection within
      subdomains 2, 3, and 4 and at the C terminus is consistent with longitudinal
      contacts of monomers within the filament helical structure as predicted by the
      Holmes model. In the absence of KCl, the extent of filament-dependent protection
      rarely reached 3-fold, consistent with a highly dynamic filament characterized by
      relatively weak interactions between actin protomers. However, in the presence of
      KCl, the extents of protection are significantly increased, consistent with a
      well-ordered, more tightly packed filament structure. Filament-dependent
      enhancements of reactivity not predicted by the Holmes model are seen for a
      peptide that overlaps the "hydrophobic plug" (H-plug) region and for a peptide
      that forms contacts with the polyphosphate moiety of the bound nucleotide.
      Overall, these data are both consistent with and complementary to a recent
      deuterium-exchange MS study of filamentous actin [Chik, J. K., and Schriemer,
      D.C. (2003) J. Mol. Biol. 334, 373-385], which also did not detect any burial of
      the H plug upon formation of filaments.

PMID- 15736928
TI  - Different modes of interaction in cyanobacterial complexes of plastocyanin and
      cytochrome f.
AB  - The highly efficient electron-transfer chain in photosynthesis demonstrates a
      remarkable variation among organisms in the type of interactions between the
      soluble electron-transfer protein plastocyanin and it partner cytochrome f. The
      complex from the cyanobacterium Nostoc sp. PCC 7119 was studied using nuclear
      magnetic resonance spectroscopy and compared to that of the cyanobacterium
      Phormidium laminosum. In both systems, the main site of interaction on
      plastocyanin is the hydrophobic patch. However, the interaction in the Nostoc
      complex is highly dependent on electrostatics, contrary to that of Phormidium,
      resulting in a binding constant that is an order of magnitude larger at low ionic
      strength for the Nostoc complex. Studies of the mixed complexes show that these
      differences in interactions are mainly attributable to the surface properties of
      the plastocyanins.

PMID- 15736929
TI  - Characterization of the product radical structure in the Co(II)-product radical
      pair state of coenzyme B12-dependent ethanolamine deaminase by using three-pulse
      2H ESEEM spectroscopy.
AB  - Molecular structural features of the product radical in the Co(II)-product
      radical pair catalytic intermediate state in coenzyme B(12)- (adenosylcobalamin-)
      dependent ethanolamine deaminase from Salmonella typhimurium have been
      characterized by using X-band three-pulse electron spin-echo envelope modulation
      (ESEEM) spectroscopy in the disordered solid state. The Co(II)-product radical
      pair state was prepared by cryotrapping holoenzyme during steady-state turnover
      on excess 1,1,2,2-(2)H(4)-aminoethanol or natural abundance, (1)H(4)
      aminoethanol. Simulation of the (2)H/(1)H quotient ESEEM (obtained at two
      microwave frequencies, 8.9 and 10.9 GHz) from the interaction of the unpaired
      electron localized at C2 of the product radical with nearby (2)H nuclei requires
      four types of coupled (2)H, which are assigned as follows: (a) a single strongly
      coupled (effective dipole distance, r(eff) = 2.3 A) (2)H in the C5' methyl group
      of 5'-deoxyadenosine, (b) two weakly coupled (r(eff) = 4.2 A) (2)H in the C5'
      methyl group, (c) one (2)H coupling from a beta-(2)H bonded to C1 of the product
      radical (isotropic hyperfine coupling, A(iso) = 4.7 MHz), and (d) a second type
      of C1 beta-(2)H coupling (A(iso) = 7.7 MHz). The two beta-(2)H couplings are
      proposed to arise from two C1-C2 rotamer states of the product radical that are
      present in approximately equal proportion. A model is presented, in which C5' is
      positioned at a distance of 3.3 A from C2, which is comparable with the C1-C5'
      distance in the Co(II)-substrate radical pair intermediate. Therefore, the
      C5'methyl group remains in close (van der Waals) contact with the substrate and
      product radical species during the radical rearrangement step of the catalytic
      cycle, and the C5' center is the sole mediator of radical pair recombination in
      ethanolamine deaminase.

PMID- 15736930
TI  - Molecular basis of the effects of chloride ion on the acid-base catalyst in the
      mechanism of pancreatic alpha-amylase.
AB  - Pig pancreatic alpha-amylase (PPA), an enzyme belonging to the alpha-amylase
      family, is involved in the degradation of starch. Like some other members of this
      family, PPA requires chloride to reach maximum activity levels. To further
      explain the mechanism of chloride activation, a crystal of wild-type PPA soaked
      with maltopentaose using a chloride-free buffer was analyzed by X-ray
      crystallography. A conspicuous reorientation of the acid/base catalyst Glu233
      residue was found to occur. The structural results, along with kinetic data, show
      that the acid/base catalyst is maintained in the active site, in an optimum
      position, pointing toward the scissile bond-atom, due to the presence of chloride
      ions. The present study therefore explains the mechanism of PPA activation by
      chloride ions.

PMID- 15736931
TI  - Mutation of arginine 228 to lysine enhances the glucosyltransferase activity of
      bovine beta-1,4-galactosyltransferase I.
AB  - Beta-1,4-galactosyltransferase I (beta4Gal-T1) normally transfers Gal from UDP
      Gal to GlcNAc in the presence of Mn(2+) ion (Gal-T activity) and also transfers
      Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency. In
      addition, alpha-lactalbumin (LA) enhances this Glc-T activity more than 25 times.
      Comparison of the crystal structures of UDP-Gal- and UDP-Glc-bound beta4Gal-T1
      reveals that the O4 hydroxyl group in both Gal and Glc moieties forms a hydrogen
      bond with the side chain carboxylate group of Glu317. The orientation of the O4
      hydroxyl of glucose causes a steric hindrance to the side chain carboxylate group
      of Glu317, accounting for the enzyme's low Glc-T activity. In this study, we show
      that mutation of Arg228, a residue in the vicinity of Glu317, to lysine (R228K
      Gal-T1) results in a 15-fold higher Glc-T activity, which is further enhanced by
      LA to nearly 25% of the Gal-T activity of the wild type. The kinetic parameters
      indicate that the main effect of the mutation of Arg228 to lysine is on the
      k(cat) of Glc-T, which increases 3-4-fold, both in the absence and in the
      presence of LA; simultaneously, the k(cat) for the Gal-T reaction is reduced 30
      fold. The crystal structure of R228K-Gal-T1 complexed with LA, UDP-Gal, and
      Mn(2+) determined at 1.9 A resolution shows that the Asp318 side chain exhibits a
      minor alternate conformation, compared to that in the wild type. This alternate
      conformation now causes a steric hindrance to the O4 hydroxyl group of the Gal
      moiety of UDP-Gal, probably causing the dissociation of UDP-Gal and the reduced
      k(cat) of the Gal-T reaction.

PMID- 15736932
TI  - Spacer-based selectivity in the binding of "two-prong" ligands to recombinant
      human carbonic anhydrase I.
AB  - Benzenesulfonamide and iminodiacetate (IDA)-conjugated Cu(2+) independently
      interact at the active site and a peripheral site of carbonic anhydrases,
      respectively [Banerjee, A. L., Swanson, M., Roy, B. C., Jia, X., Haldar, M. K.,
      Mallik, S., and Srivastava, D. K. (2004) J. Am. Chem. Soc. 126, 10875-10883]. By
      attaching IDA-bound Cu(2+) to benzenesulfonamide via different chain length
      spacers, we synthesized two "two-prong" ligands, L1 and L2, in which the
      distances between Cu(2+) and NH(2) group of sulfonamide were 29 and 22 A,
      respectively. We compared the binding affinities of L1 and L2, vis-a-vis their
      parent compound, benzenesulfonamide, for recombinant human carbonic anhydrase I
      (hCA-I) by performing the fluorescence titration and steady-state kinetic
      experiments. The experimental data revealed that whereas the binding affinity of
      L1 for hCA-I was similar to that of benzenesulfonamide, the binding affinity of
      L2 was approximately 2 orders of magnitude higher, making L2 one of the most
      potent ligands or inhibitors of hCA-I. Since the enhanced binding or inhibitory
      potency of L2 is diminished (to the level of benzenesulfonamide) either in the
      presence of EDTA or upon treatment of the enzyme with diethyl pyrocarbonate, it
      is proposed that Cu(2+) of L2 interacts with one of the surface-exposed histidine
      residues of the enzyme. A cumulative account of the experimental data leads to
      the suggestion that the differential binding of L1 versus L2 to hCA-I is encoded
      in the chain length of the spacer moiety.

PMID- 15736933
TI  - Insights into the base catalysis exerted by the DD-transpeptidase from
      Streptomyces K15: a molecular dynamics study.
AB  - Herein, we present results from molecular dynamics simulations of the DD
      transpeptidase/penicillin-binding protein from Streptomyces K15 and its Michaelis
      complex with benzylpenicillin. For the apo-enzyme, six different configurations
      of the active site were modeled in aqueous solution and their relative
      stabilities were estimated by means of quantum mechanical energy calculations.
      The energetically most stable configuration has a neutral Lys(213) residue. In
      this configuration, the nucleophilic Ser(35) hydroxyl group interchanges with a
      water molecule in the "oxy-anion hole" and the Lys(38)/Lys(213) ammonium/amino
      groups are connected through the Ser(96) hydroxyl group. Subsequently, the enzyme
      penicillin complexes corresponding to the four most stable configurations of the
      apo-enzyme were modeled. In the presence of the beta-lactam antibiotic, the
      configuration with a neutral Lys(38) residue is favored energetically and shows
      the best orientation for nucleophilic attack. In addition, a very stable contact
      between the Ser(35) hydroxyl group and the neutral amino group of Lys(38)
      supports the assignation of Lys(38) as the base catalyst for the acylation step.
      Finally, some mechanistic implications of enzyme-inhibitor contacts involving the
      benzylpenicillin carboxylate group are also discussed.

PMID- 15736934
TI  - Interaction of phosphonate analogues of the tetrahedral reaction intermediate
      with 5-enolpyruvylshikimate-3-phosphate synthase in atomic detail.
AB  - The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the
      penultimate step of the shikimate pathway and is the target of the broad-spectrum
      herbicide glyphosate. Since the functionality of the shikimate pathway is vital
      not only for plants but also for microorganisms, EPSPS is considered a
      prospective target for the development of novel antibiotics. We have kinetically
      analyzed and determined the crystal structures of Escherichia coli EPSPS
      inhibited by (R)- and (S)-configured phosphonate analogues of the tetrahedral
      reaction intermediate. Both diastereomers are competitive inhibitors with respect
      to the substrates of the EPSPS reaction, shikimate-3-phosphate (S3P) and
      phosphoenolpyruvate (PEP). Remarkably, the (S)-phosphonate (K(iS3P) = 750 nM),
      whose configuration corresponds to that of the genuine tetrahedral intermediate,
      is a much weaker inhibitor than the (R)-phosphonate analogue (K(iS3P) = 16 nM).
      The crystal structures of EPSPS liganded with the (S)- and (R)-phosphonates, at
      1.5 and 1.9 A resolution, respectively, revealed that binding of the (R)
      phosphonate induces conformational changes of the strictly conserved residues
      Arg124 and Glu341 within the active site. This appears to give rise to
      substantial structural alterations in the amino-terminal globular domain of the
      enzyme. By contrast, binding of the (S)-phosphonate renders the enzyme structure
      unchanged. Thus, EPSPS may facilitate the tight binding of structurally diverse
      ligands through conformational flexibility. Molecular docking calculations did
      not explain why the (R)-phosphonate is the better inhibitor. Therefore, we
      propose that the structural events during the open-closed transition of EPSPS are
      altered as a result of inhibitor action.

PMID- 15736935
TI  - -NH-dansyl isocolchicine exhibits a significantly improved tubulin-binding
      affinity and microtubule inhibition in comparison to isocolchicine by binding
      tubulin through its A and B rings.
AB  - Structure-activity relationship studies have established that the A and C rings
      of colchicine comprise the minimum structural feature necessary for high affinity
      drug-tubulin binding. Thus, colchicine acts as a bifunctional ligand by making
      two points of attachment to the protein. Furthermore, analogues belonging to the
      iso series of colchicine are virtually inactive in binding to tubulin and
      inhibiting microtubule assembly. In the present study, we found that the
      substitution of a hydrophobic dansyl group on the B-ring side chain (C7 position)
      of isocolchicine reverses the structural alterations at the C ring and the newly
      synthesized -NH-dansyl isocolchicine restores the lost biological activity of the
      compound. It inhibits microtubule assembly efficiently with an IC(50) value of 10
      microM and competes with [(3)H]colchicine for binding to tubulin. Moreover,
      although -NH-dansyl colchicine binding to tubulin involves two steps, the -NH
      dansyl isocolchicine-tubulin interaction has been found to occur via a one-step
      process. Also, the affinity constant of the -NH-dansyl isocolchicine-tubulin
      interaction is roughly only 3 times lower than that of the -NH-dansyl colchicine
      tubulin interaction. These results suggest that the enhanced microtubule
      inhibitory ability of -NH-dansyl isocolchicine is therefore related to the
      affinity of the drug-tubulin interaction and not to any conformational changes
      upon binding tubulin. We also observed that the competition of -NH-dansyl
      isocolchicine with [(3)H]colchicine for binding to tubulin was dependent on the
      tubulin concentration. In conclusion, this paper for the first time indicates
      that a biologically active bifuntional colchicine analogue can be designed where
      the drug binds tubulin through its A and B rings, while the C ring remains
      inactive.

PMID- 15736936
TI  - Cholesterol binding to cytochrome P450 7A1, a key enzyme in bile acid
      biosynthesis.
AB  - The conversion of cholesterol to 7alpha-hydroxycholesterol catalyzed by
      cytochrome P450 7A1 (CYP7A1) initiates the major pathway for cholesterol
      elimination in mammals. In the present work we focused on identification of
      determinants of the CYP7A1 substrate specificity inside the active site using a
      homology model with a novel P450-fold, site-directed mutagenesis, and substrate
      binding and kinetic studies. Forty-one mutants, encompassing twenty-six amino
      acid residues, were generated and characterized, and of these, seven residues
      appear to determine cholesterol binding in the active site. In addition, four
      cholesterol derivatives were used as active site probes in the wild type and the
      seven mutant enzymes, and the spectral binding constants and products were
      analyzed. It was concluded that Asn288 in the I helix plays a key role in the
      P450-cholesterol contacts by hydrogen bonding to the steroid 3beta-hydroxyl,
      while Val280 and Ala284 are beside and the Trp283 is above the steroid nucleus
      orienting the cholesterol molecule. Leu360 and Ala358 between the K helix and the
      beta1-4 strand and Leu485 in the beta4 sheet-turn appear to define the size of
      the active site over the heme pyrrole ring A, thus limiting the orientation and
      size of the substrate at the steroid A ring. Additionally, the A358V mutant was
      found to form two new products, one being 7beta-hydroxycholesterol. Our data
      indicate that a tight fit of cholesterol in the enzyme active site is in part
      responsible for the high efficiency of cholesterol turnover by CYP7A1.

PMID- 15736937
TI  - Directed coevolution of stability and catalytic activity in calcium-free
      subtilisin.
AB  - We have coevolved high activity and hyperstability in subtilisin by sequentially
      randomizing 12 amino acid positions in calcium-free subtilisin. The optimal amino
      acid for each randomized site was chosen based on stability and catalytic
      properties and became the parent clone for the next round of mutagenesis.
      Together, the 12 selected mutations increased the half-life of calcium-free
      subtilisin at elevated temperature by 15,000-fold. The catalytic properties of
      the mutants were examined against a range of substrates. In general, only
      mutations occurring at or near the substrate-binding surface have measurable
      effects on catalytic constants. No direct influence of stability on catalytic
      properties was observed. A high-stability mutant, Sbt140, was a more efficient
      enzyme in terms of k(cat)/K(m) than a commercial version of subtilisin across a
      range of substrates but had a lower k(cat) against tight-binding substrates. The
      reason for this behavior was discerned by examining microscopic rate constants
      for the hydrolysis of a tight-binding peptide substrate. Burst kinetics were
      observed for this substrate, indicating that acylation is not rate-limiting.
      Although acylation occurs at the rate of substrate binding, k(cat) is attenuated
      by the slow release of the N-terminal product. Natural evolution appears to have
      optimized catalytic activity against a range of sequences by achieving a balance
      between substrate binding and the rate of release of the N-terminal product.

PMID- 15736938
TI  - Dimeric transthyretin variant assembles into spherical neurotoxins.
AB  - Familial amyloidotic polyneuropathy is a hereditary autosomal-dominant disease in
      which the deposited transthyretin fibrils are derived from amyloidogenic
      mutation. We investigated structure and stability of a human Ser112Ile
      transthyretin variant and showed that the Ser112Ile variant exists as a dimer
      having nonnative tertiary structure at physiological pH. In addition, the dimeric
      Ser112Ile assembles into a spherical aggregate and exerts cytotoxicity in a human
      neuroblastoma cell line. Our results suggest the importance of an unstable
      dimeric structure in forming spherical aggregates that will induce cell death.

PMID- 15736939
TI  - The effects of mutation on the regulatory properties of phospholamban in co
      reconstituted membranes.
AB  - Reconstitution into proteoliposomes is a powerful method for studying calcium
      transport in a chemically pure membrane environment. By use of this approach, we
      have studied the regulation of Ca(2+)-ATPase by phospholamban (PLB) as a function
      of calcium concentration and PLB mutation. Co-reconstitution of PLB and Ca(2+)
      ATPase revealed the expected effects of PLB on the apparent calcium affinity of
      Ca(2+)-ATPase (K(Ca)) and unexpected effects of PLB on maximal activity (V(max)).
      Wild-type PLB, six loss-of-function mutants (L7A, R9E, I12A, N34A, I38A, L42A),
      and three gain-of-function mutants (N27A, L37A, and I40A) were evaluated for
      their effects on K(Ca) and V(max). With the loss-of-function mutants, their
      ability to shift K(Ca) correlated with their ability to increase V(max). A total
      loss-of-function mutant, N34A, had no effect on K(Ca) of the calcium pump and
      produced only a marginal increase in V(max). A near-wild-type mutant, I12A,
      significantly altered both K(Ca) and V(max) of the calcium pump. With the gain-of
      function mutants, their ability to shift K(Ca) did not correlate with their
      ability to increase V(max). The "super-shifting" mutants N27A, L37A, and I40A
      produced a large shift in K(Ca) of the calcium pump; however, L37A decreased
      V(max), while N27A and I40A increased V(max). For wild-type PLB, phosphorylation
      completely reversed the effect on K(Ca), but had no effect on V(max). We conclude
      that PLB increases V(max) of Ca(2+)-ATPase, and that the magnitude of this effect
      is sensitive to mutation. The mutation sensitivity of PLB Asn(34) and Leu(37)
      identifies a region of the protein that is responsible for this regulatory
      property.

PMID- 15736940
TI  - Oligomeric state and mode of self-association of Thermotoga maritima ribosomal
      stalk protein L12 in solution.
AB  - The "stalk" of the prokaryotic 50S ribosomal subunit is comprised of four copies
      of the protein L7/L12. In Escherichia coli, L7/L12 is a dimeric protein at
      micromolar concentrations, which is able to undergo rapid subunit exchange. A
      recent structural study indicated a tetrameric arrangement of the L12 proteins
      isolated from Thermotoga maritima, in which the proteins engaged in two different
      dimerization modes. In one mode, the two monomers of L12 form a tight symmetric
      and parallel dimer held together by a four-helix bundle, which encompasses the
      hinge region between the N- and C-terminal domains. In the other mode, the two
      monomers bind through their N-terminal region in an antiparallel configuration,
      in which one monomer comprises an alpha-helical hinge and the other monomer
      adopts an elongated shape with an unfolded hinge region. Presently, it is unclear
      which dimer contact prevails in solution and on the ribosome. Using cysteine
      mutants of T. maritima labeled with fluorescent probes, we investigated the mode
      of interactions between L12 subunits. Data from Forster resonance energy transfer
      experiments support a dimerization of L12 in solution, in which two monomers bind
      through their N-terminal region in an antiparallel configuration. We also
      demonstrate that the rate of subunit exchange in T. maritima L12 is significantly
      slower at 25 degrees C than that in the E. coli system. The exchange rate
      increases with increasing temperature and approaches the one observed for the E.
      coli system at 50 degrees C. Possible factors responsible for this difference are
      discussed.

PMID- 15736941
TI  - Ultraviolet resonance Raman studies reveal the environment of tryptophan and
      tyrosine residues in the native and partially folded states of the E colicin
      binding immunity protein Im7.
AB  - Understanding the nature of partially folded proteins is a challenging task that
      is best accomplished when several techniques are applied in combination. Here we
      present ultraviolet resonance Raman (UVRR) spectroscopy studies of the E colicin
      binding immunity proteins, Im7* and Im9*, together with a series of variants of
      Im7* that are designed to trap a partially folded state at equilibrium. We show
      that the environments of the tryptophan and tyrosine residues in native wild-type
      Im7* and Im9* are indistinguishable, in contrast with models for their structures
      based on X-ray and NMR methods. In addition, we show that there is a general
      increase in the hydrophobicity in the environment of Trp75 in all of the variants
      compared with wild-type Im7*. These data suggest that a significant rearrangement
      of the tryptophan pocket occurs in the variants, which, together with an overall
      decrease in solvent accessibility of Trp75 as judged by time-resolved
      fluorescence lifetime measurements and fluorescence quenching experiments,
      rationalize the unusual fluorescence properties of the variants reported
      previously. The data highlight the power of UVRR in analyzing the structural
      properties of different conformational states of the same protein and reveal new
      information about the structural rearrangements occurring during Im7* folding,
      not possible using other spectroscopic methods alone. Finally, we describe a
      previously unreported dependence of the tryptophan Fermi doublet on excitation
      wavelength in the ultraviolet region revealed by these protein spectra. We
      corroborated this observation using tryptophan-containing model compounds and
      conclude that the conventional interpretation of this UVRR feature at these
      wavelengths is unreliable.

PMID- 15736942
TI  - Synthesis and characterization of 4-methoxy-7-nitroindolinyl-D-aspartate, a caged
      compound for selective activation of glutamate transporters and N-methyl-D
      aspartate receptors in brain tissue.
AB  - The D-isomer of aspartate is efficiently transported by high-affinity Na(+)/K(+)
      dependent glutamate transporters and is an effective ligand of N-methyl-d
      aspartate (NMDA) receptors. To facilitate analysis of the regulation of these
      proteins in their native membranes, we synthesized a photolabile analogue of D
      aspartate, 4-methoxy-7-nitroindolinyl-D-aspartate (MNI-D-aspartate). This
      compound was photolyzed with a quantum efficiency of 0.09 at pH 7.4. Photorelease
      of d-aspartate in acute hippocampal slices through brief (1 ms) UV laser
      illumination of MNI-d-aspartate triggered rapidly activating currents in
      astrocytes that were inhibited by the glutamate transporter antagonist DL-threo
      beta-benzyloxyaspartic acid (TBOA), indicating that they resulted from
      electrogenic uptake of D-aspartate. These transporter currents exhibited a
      distinct tail component that was approximately 2% of the peak current, which may
      result from the release of K(+) into the extracellular space during counter
      transport. MNI-D-aspartate was neither an agonist nor an antagonist of glutamate
      transporters at concentrations up to 500 muM and was stable in aqueous solution
      for several days. Glutamate transporter currents were also elicited in Bergmann
      glial cells and Purkinje neurons of the cerebellum in response to photolysis of
      MNI-D-aspartate, indicating that this compound can be used for monitoring the
      occupancy and regulation of glutamate transporters in different brain regions.
      Photorelease of D-aspartate did not activate alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)/kainate receptors or metabotropic glutamate
      receptors (mGluRs) in neurons, but resulted in the selective, but transient,
      activation of NMDA receptors in hippocampal pyramidal neurons; MNI-D-aspartate
      was not an antagonist of NMDA receptors. These results indicate that MNI-D
      aspartate also may be useful for studying the regulation of NMDA receptors at
      excitatory synapses.

PMID- 15736943
TI  - Structure of an oligodeoxynucleotide containing a butadiene oxide-derived N1 beta
      hydroxyalkyl deoxyinosine adduct in the human N-ras codon 61 sequence.
AB  - The solution structure of the N1-(1-hydroxy-3-buten-2(S)-yl)-2'-deoxyinosine
      adduct arising from the alkylation of adenine N1 by butadiene epoxide (BDO),
      followed by deamination to deoxyinosine, was determined, in the
      oligodeoxynucleotide d(CGGACXAGAAG).d(CTTCTCGTCCG). This oligodeoxynucleotide
      contained the BDO adduct at the second position of codon 61 of the human N-ras
      protooncogene, and was named the ras61 S-N1-BDO-(61,2) adduct. (1)H NMR revealed
      a weak C(5) H1' to X(6) H8 NOE, followed by an intense X(6) H8 to X(6) H1' NOE.
      Simultaneously, the X(6) H8 to X(6) H3' NOE was weak. The resonance arising from
      the T(17) imino proton was not observed. (1)H NOEs between the butadiene moiety
      and the DNA positioned the adduct in the major groove. Structural refinement
      based upon a total of 364 NOE-derived distance restraints yielded a structure in
      which the modified deoxyinosine was in the high syn conformation about the
      glycosyl bond, and T(17), the complementary nucleotide, was stacked into the
      helix, but not hydrogen bonded with the adducted inosine. The refined structure
      provided a plausible hypothesis as to why this N1 deoxyinosine adduct strongly
      coded for the incorporation of dCTP during trans lesion DNA replication, both in
      Escherichia coli [Rodriguez, D. A., Kowalczyk, A., Ward, J. B. J., Harris, C. M.,
      Harris, T. M., and Lloyd, R. S. (2001) Environ. Mol. Mutagen. 38, 292-296], and
      in mammalian cells [Kanuri, M., Nechev, L. N., Tamura, P. J., Harris, C. M.,
      Harris, T. M., and Lloyd, R. S. (2002) Chem. Res. Toxicol. 15, 1572-1580].
      Rotation of the N1 deoxyinosine adduct into the high syn conformation may
      facilitate incorporation of dCTP via Hoogsteen-type templating with deoxyinosine,
      thus generating A-to-G mutations.

PMID- 15736944
TI  - Base selectivity is impaired by mutants that perturb hydrogen bonding networks in
      the RB69 DNA polymerase active site.
AB  - To investigate the molecular basis for the selective utilization of nucleoside
      triphosphates complementary to templating bases, by RB69 DNA polymerase (RB69
      pol), we constructed a set of mutants that we predicted would perturb the "floor"
      of the nascent base-pairing interface in the enzyme. We then determined the pre
      steady-state kinetic parameters for the incorporation of complementary and
      noncomplementary dNTPs by the exo(-) form of RB69 pol and its mutants. We found
      that the Y567A mutant had the same K(d) and k(pol) values for incorporation of C
      versus G as the wild-type exo(-) enzyme; however, the k(pol)/K(d) ratio for G
      versus G incorporation with the Y567A mutant was 10 times higher than the
      k(pol)/K(d) efficiency of G versus G incorporation using the exo(-) RB69 pol. The
      reduced level of discrimination by the Y567A mutant against incorporation of
      mismatched bases was also seen with the Y391A mutant. Stopped-flow fluorescence
      was also employed to monitor rates of putative conformational changes with the
      exo(-) RB69 pol and its mutants using a primer-template complex containing 2
      aminopurine. The rates of fluorescence changes were equal to or greater than the
      rates of the rapid chemical quench, indicating that we were monitoring a process
      occurring before or during the phosphoryl transfer reaction. We have interpreted
      our results within the context of the crystal structure of the RB69 pol ternary
      complex [Franklin, M. C., et al. (2001) Cell 105, 657-667].

PMID- 15736945
TI  - Acarbose rearrangement mechanism implied by the kinetic and structural analysis
      of human pancreatic alpha-amylase in complex with analogues and their elongated
      counterparts.
AB  - A mechanistic study of the poorly understood pathway by which the inhibitor
      acarbose is enzymatically rearranged by human pancreatic alpha-amylase has been
      conducted by structurally examining the binding modes of the related inhibitors
      isoacarbose and acarviosine-glucose, and by novel kinetic measurements of all
      three inhibitors under conditions that demonstrate this rearrangement process.
      Unlike acarbose, isoacarbose has a unique terminal alpha-(1-6) linkage to glucose
      and is found to be resistant to enzymatic rearrangement. This terminal glucose
      unit is found to bind in the +3 subsite and for the first time reveals the
      interactions that occur in this part of the active site cleft with certainty.
      These results also suggest that the +3 binding subsite may be sufficiently
      flexible to bind the alpha-(1-6) branch points in polysaccharide substrates, and
      therefore may play a role in allowing efficient cleavage in the direct vicinity
      of such junctures. Also found to be resistant to enzymatic rearrangement was
      acarviosine-glucose, which has one fewer glucose unit than acarbose.
      Collectively, structural studies of all three inhibitors and the specific
      cleavage pattern of HPA make it possible to outline the simplest sequence of
      enzymatic reactions likely involved upon acarbose binding. Prominent features
      incorporated into the starting structure of acarbose to facilitate the synthesis
      of the final tightly bound pseudo-pentasaccharide product are the restricted
      availability of hydrolyzable bonds and the placement of the transition state-like
      acarviosine group. Additional "in situ" experiments designed to elongate and
      thereby optimize isoacarbose and acarviosine-glucose inhibition using the
      activated substrate alphaG3F demonstrate the feasibility of this approach and
      that the principles outlined for acarbose rearrangement can be used to predict
      the final products that were obtained.

PMID- 15736946
TI  - Insight into ribonuclease A domain swapping by molecular dynamics unfolding
      simulations.
AB  - Bovine pancreatic ribonuclease (RNase A) deserves a special place among the
      numerous proteins that form oligomers by three-dimensional domain swapping. In
      fact, under destabilizing conditions and at high protein concentrations, it can
      swap two different domains, the N-terminal alpha-helix or the C-terminal beta
      strand, leading to dimers with different quaternary structures. With the change
      in the unfolding conditions, the relative abundance of the two dimers varies, and
      the prevalence of one dimer over the other is inverted. To investigate the
      dynamic behavior of the termini, four independent 10 ns high-temperature
      molecular dynamics simulations of RNase A were carried out at two different pH
      values in an attempt to reproduce the experimental conditions of neutral and very
      low pH that favor the formation of the N- and C-terminal domain-swapped dimers,
      respectively. In agreement with experimental data, under mild unfolding
      conditions, a partial or complete opening of the N-terminal arm is observed,
      whereas the dislocation of the C-terminus away from the core of the structure
      occurs only during the low-pH simulations. Furthermore, the picture emerging from
      this study indicates that the same protein can have different pathways for domain
      swapping. Indeed, in RNase A the C-terminal swapping requires a substantial
      unfolding of the monomers, whereas the N-terminal swapping can occur through only
      partial unfolding.

PMID- 15736947
TI  - Kinetic and structural properties of disulfide engineered phospholipase A2:
      insight into the role of disulfide bonding patterns.
AB  - The family of secreted 14 kDa phospholipase A(2) (PLA2) enzymes have a common
      motif for the catalytic site but differ in their disulfide architecture. The
      functional significance of such structural changes has been analyzed by comparing
      the kinetic and spectroscopic properties of a series of disulfide mutants
      engineered into the sequence of pig pancreatic IB PLA2 to resemble the mammalian
      paralogues of the PLA2 family [Janssen et al. (1999) Eur. J. Biochem. 261, 197
      207, 1999]. We report a detailed comparison of the functional parameters of pig
      iso-PLA2, as well as several of the human homologues, with these disulfide
      engineered mutants of pig IB PLA2. The crystal structure of the ligand free and
      the active site inhibitor-MJ33 bound forms of PLA2 engineered to have the
      disulfide bonding pattern of group-X (eng-X) are also reported and compared with
      the structure of group-IB and human group-X PLA2. The engineered mutants show
      noticeable functional differences that are rationalized in terms of spectroscopic
      properties and the differences detected in the crystal structure of eng-X. A
      major difference between the eng-mutants is in the calcium binding to the enzyme
      in the aqueous phase, which also influences the binding of the active site
      directed ligands. We suggest that the disulfide architecture of the PLA2
      paralogues has a marginal influence on interface binding. In this comparison, the
      modest differences observed in the interfacial kinetics are attributed to the
      changes in the side chain residues. This in turn influences the coupling of the
      catalytic cycle to the calcium binding and the interfacial binding event.

PMID- 15736948
TI  - Metal-induced structural organization and stabilization of the metalloregulatory
      protein MntR.
AB  - MntR is a metalloregulatory protein that helps to modulate the level of manganese
      in Bacillus subtilis. MntR shows a metal-response profile distinct from other
      members of the DtxR family of metalloregulatory proteins, which are generally
      considered to be iron(II)-activated. As part of an ongoing effort to elucidate
      the mechanism and metal-selectivity of MntR, several biophysical studies on wild
      type MntR and two active site mutants, MntR E99C and MntR D8M, have been
      performed. Using circular dichroism (CD) spectroscopy, the thermal stability of
      these proteins has been examined in the presence of various divalent metal ions.
      Fluorescence intensity measurements of 8-anilino-1-naphthalenesulfonic acid (ANS)
      were monitored to examine the folding of these proteins in the presence of
      different metal ions. These experiments indicate that MntR undergoes a
      significant conformational change upon metal binding that results in
      stabilization of the protein structure. These studies also show that the MntR D8M
      active site mutation causes a detrimental effect on the metal-responsiveness of
      this protein. Fluorescence anisotropy experiments have been performed to quantify
      the extent of metal-activated DNA binding by these proteins to two different
      cognate recognition sequences. Binding of MntR and MntR E99C to the mntA cognate
      sequence closely parallels that of the mntH operator, confirming that the
      proteins bind both sequences with comparable affinity depending on the activating
      metal ion. Fluorescence anisotropy experiments on MntR D8M indicate significantly
      impaired DNA binding, providing additional evidence that MntR D8M is a
      dysfunctional regulator.

PMID- 15736949
TI  - Quantitative analysis of substrate specificity of haloalkane dehalogenase LinB
      from Sphingomonas paucimobilis UT26.
AB  - Haloalkane dehalogenases are microbial enzymes that cleave a carbon-halogen bond
      in halogenated compounds. The haloalkane dehalogenase LinB, isolated from
      Sphingomonas paucimobilis UT26, is a broad-specificity enzyme. Fifty-five
      halogenated aliphatic and cyclic hydrocarbons were tested for dehalogenation with
      the LinB enzyme. The compounds for testing were systematically selected using a
      statistical experimental design. Steady-state kinetic constants K(m) and k(cat)
      were determined for 25 substrates that showed detectable cleavage by the enzyme
      and low abiotic hydrolysis. Classical quantitative structure-activity
      relationships (QSARs) were used to correlate the kinetic constants with molecular
      descriptors and resulted in a model that explained 94% of the experimental data
      variability. The binding affinity of the tested substrates for this haloalkane
      dehalogenase correlated with hydrophobicity, molecular surface, dipole moment,
      and volume:surface ratio. Binding of the substrate molecules in the active site
      pocket of LinB depends nonlinearly on the size of the molecules. Binding affinity
      increases with increasing substrate size up to a chain length of six carbon atoms
      and then decreases. Comparative binding energy (COMBINE) analysis was then used
      to identify amino acid residues in LinB that modulate its substrate specificity.
      A model with three statistically significant principal components explained 95%
      of the experimental data variability. van der Waals interactions between
      substrate molecules and the enzyme dominated the COMBINE model, in agreement with
      the importance of substrate size in the classical QSAR model. Only a limited
      number of protein residues (6-8%) contribute significantly to the explanation of
      variability in binding affinities. The amino acid residues important for
      explaining variability in binding affinities are as follows: (i) first-shell
      residues Asn38, Asp108, Trp109, Glu132, Ile134, Phe143, Phe151, Phe169, Val173,
      Trp207, Pro208, Ile211, Leu248, and His272, (ii) tunnel residues Pro144, Asp147,
      Leu177, and Ala247, and (iii) second-shell residues Pro39 and Phe273. The tunnel
      and the second-shell residues represent the best targets for modulating
      specificity since their replacement does not lead to loss of functionality by
      disruption of the active site architecture. The mechanism of molecular adaptation
      toward a different specificity is discussed on the basis of quantitative
      comparison of models derived for two protein family members.

PMID- 15736950
TI  - Reversible transition between the surface trimer and membrane-inserted monomer of
      annexin 12.
AB  - Under mildly acidic conditions, annexin 12 (ANX) inserts into lipid membranes to
      form a transbilayer pore [Langen, R., et al. (1998) Proc. Natl. Acad. Sci. U.S.A.
      95, 14060]. In this study, we have addressed the question of the oligomeric state
      of ANX in this transbilayer conformation by means of Forster-type resonance
      energy transfer (FRET). Two single-cysteine mutants (K132C and N244C) were
      labeled with either Alexa-532 (donor) or Alexa-647 (acceptor). The labels were
      positioned at the sites thought to be on the cis side of the known transmembrane
      regions [Ladokhin, A. S., et al. (2002) Biochemistry 41, 13617]. If the pore were
      comprised of an annexin oligomer, efficient energy transfer should be observed.
      Fluorescence excitation spectra of several mixtures of donor- and acceptor
      labeled ANX were recorded under various conditions. Spectroscopic hallmarks of
      oligomerization-related FRET were established by following a well-documented
      transition of ANX from the soluble monomer to surface trimer upon addition of
      calcium at neutral pH. These hallmarks, however, were not detected for the
      membrane-inserted form of ANX at pH 4.5, suggesting that the transbilayer form is
      a monomer. This implies that the pore is formed by several transmembrane regions
      of the same ANX molecule. FRET and other fluorescence experiments demonstrate
      that the transitions between the surface trimer and membrane-inserted monomer are
      reversible. This reversibility, in combination with the absence of
      oligomerization in the water-soluble and inserted state, makes ANX a good
      experimental model for thermodynamic studies of folding and stability of membrane
      proteins.

PMID- 15736951
TI  - Microsecond-to-millisecond conformational dynamics demarcate the GluR2 glutamate
      receptor bound to agonists glutamate, quisqualate, and AMPA.
AB  - Chemical shift changes and internal motions on microsecond-to-millisecond time
      scales of the S1S2 ligand-binding domain of the GluR2 ionotropic glutamate
      receptor have been studied by NMR spectroscopy in the presence of the agonists
      glutamic acid (glutamate), quisqualic acid (quisqualate), and alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). Although the crystal
      structures of the three agonist-bound forms of GluR2 S1S2 ligand-binding domain
      are very similar, chemical shift changes imply that AMPA-bound GluR2 S1S2 is
      conformationally distinct from glutamate- and quisqualate-bound forms of GluR2
      S1S2. NMR spin relaxation measurements for backbone amide (15)N nuclei reveal
      that GluR2 S1S2 exhibits reduced chemical exchange line broadening, resulting
      from microsecond-to-millisecond conformational dynamics, in AMPA-bound compared
      to glutamate- and quisqualate-bound states. The largest changes in line
      broadening are observed for two regions of GluR2 S1S2: Val683 and the segment
      around Lys716-Cys718. The differences in binding affinity of these agonists do
      not explain the differences in microsecond-to-millisecond conformational dynamics
      because quisqualate and AMPA bind with similar affinities that are 10-fold
      greater than the affinity of glutamate. Differences in conformational mobility
      may reflect differences in the binding mode of AMPA in the GluR2 S1S2 active site
      compared to the other two ligands. The sites of conformational mobility in GluR2
      S1S2 imply that subtle differences exist between the agonists glutamate,
      quisqualate, and AMPA in modulating glutamate receptor function.

PMID- 15736952
TI  - Receptor-antagonist interactions in the complexes of agouti and agouti-related
      protein with human melanocortin 1 and 4 receptors.
AB  - The molecular interactions between human melanocortin receptor-1 and -4 (hMC1R
      and hMC4R) and their endogenous antagonists, agouti signaling protein (ASIP) and
      agouti-related protein (AGRP), were assessed by studying the effects of site
      directed mutations on the binding affinity of (125)I-ASIP[90-132(L89Y)] and
      (125)I-AGRP(86-132). Mutations of homologous residues from transmembrane helices
      (TMHs) 3 and 6 and extracellular loop (EL) 3 (D121A, T124A, F257A, and F277M in
      hMC1R and D126A, I129A F261A, and M281F in hMC4R) impaired binding of both
      antagonists to hMC4R and binding of the ASIP fragment to hMC1R. However, the
      mutations in TMH2 (E94A in hMC1R and E100A in hMC4R), TMH7 (F280A in hMC1R and
      F284A in hMC4R), and EL2 (Y183S, H184S, and D184H in hMC1R) only significantly
      affected binding of the ASIP fragment. The dependence of agonist binding on the
      dithiothreitol concentration followed a monophasic curve for wild-type hMC4R and
      its C40A, C271A, and C279A mutants and a biphasic curve for hMC1R, suggesting the
      presence of at least one structurally and functionally essential disulfide bond
      in both wild-type receptors and the hMC4R mutants. Models of complexes of both
      receptors with the ASIP fragment and hMC4R with the AGRP fragment were calculated
      using constraints from the experimental structures of rhodopsin and AGRP
      fragments, a set of deduced hydrogen bonds, supplemented by two proposed
      disulfide bridges and receptor-ligand contacts, derived from our mutagenesis
      data. In the models of the ASIP fragment complexed with both receptors, the core
      ligand tripeptide, Arg-Phe-Phe, positioned between TMHs 3 and 6, is shifted
      toward TMHs 2 and 7 relative to its position in the AGRP-hMC4R model, while the N
      terminal loop and two central disulfides of the antagonists interact with EL2 of
      the receptors.

PMID- 15736953
TI  - Identification of key residues in the A-Raf kinase important for phosphoinositide
      lipid binding specificity.
AB  - Raf kinases are involved in regulating cellular signal transduction pathways in
      response to a wide variety of external stimuli. Upstream signals generate
      activated Ras-GTP, important for the relocalization of Raf kinases to the
      membrane. Upon full activation, Raf kinases phosphorylate and activate downstream
      kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. The Raf
      family of kinases has three members, Raf-1, B-Raf, and A-Raf. The ability of Raf
      1 and B-Raf to bind phosphatidylserine (PS) and phosphatidic acid (PA) has been
      show to facilitate Raf membrane associations and regulate Raf kinase activity. We
      have characterized the lipid binding properties of A-Raf, as well as further
      characterized those of Raf-1. Both A-Raf and Raf-1 were found to bind to 3-, 4-,
      and 5-monophosphorylated phosphoinositides [PI(3)P, PI(4)P, and PI(5)P] as well
      as phosphatidylinositol 3,5-bisphosphate [PI(3,5)P(2)]. In addition, A-Raf also
      bound specifically to phosphatidylinositol 4,5- and 3,4-bisphosphates
      [PI(4,5)P(2) and PI(3,4)P(2)] and to PA. A mutational analysis of A-Raf localized
      the PI(4,5)P(2) binding site to two basic residues (K50 and R52) within the Ras
      binding domain. Additionally, an A-Raf mutant lacking the first 199 residues
      [i.e., the entire conserved region 1 (CR1) domain] bound the same phospholipids
      as full-length Raf-1. This suggests that a second region of A-Raf between amino
      acids 200 and 606 was responsible for interactions with the monophosphorylated
      PIs and PI(3,5)P(2). These results raise the possibility that Raf-1 and A-Raf
      bind to specific phosphoinositides as a mechanism to localize them to particular
      membrane microdomains rich in these phospholipids. Moreover, the differences in
      their lipid binding profiles could contribute to their proposed isoform-specific
      Raf functions.

PMID- 15736954
TI  - Kinetic analyses reveal multiple steps in forming TonB-FhuA complexes from
      Escherichia coli.
AB  - FhuA, an outer membrane receptor of Escherichia coli, facilitates transport of
      hydroxamate siderophores and siderophore-antibiotic conjugates. The cytoplasmic
      membrane complex TonB-ExbB-ExbD provides energy for transport via the proton
      motive force. This energy is transduced by protein-protein interactions between
      TonB and FhuA, but the molecular determinants of these interactions remain
      uncharacterized. Our analyses of FhuA and two recombinant TonB species by surface
      plasmon resonance revealed that TonB undergoes a kinetically limiting
      rearrangement upon initial interaction with FhuA: an intermediate TonB-FhuA
      complex of 1:1 stoichiometry was detected. The intermediate then recruits a
      second TonB protein. Addition of ferricrocin, a FhuA-specific ligand, enhanced
      amounts of the 2:1 complex but was not essential for its formation. To assess the
      role of the cork domain of FhuA in forming a 2:1 TonB-FhuA complex, we tested a
      FhuA deletion (residues 21-128) for its ability to interact with TonB. Analytical
      ultracentrifugation demonstrated that deletion of this region of the cork domain
      resulted in a 1:1 complex. Furthermore, the high-affinity 2:1 complex requires
      the N-terminal region of TonB. Together these in vitro experiments establish that
      TonB-FhuA interactions require sequential steps of kinetically limiting
      rearrangements. Additionally, domains that contribute to complex formation were
      identified in TonB and in FhuA.

PMID- 15736955
TI  - Transport of divalent transition-metal ions is lost in small-intestinal tissue of
      b/b Belgrade rats.
AB  - Belgrade rats exhibit microcytic, hypochromic anemia and systemic iron deficiency
      due to a glycine-to-arginine mutation at residue 185 in a metal ion transporter
      of a divalent metal transporter/divalent cation transporter/solute carrier 11
      group A member 2 or 3 (DMT1/DCT1/SLC11A2), a member of the natural-resistance
      associated macrophage protein (Nramp) family. By use of rabbit duodenal tissue, a
      calcein fluorescence assay has previously been developed to assess transport of
      divalent metal ions across the small-intestinal brush border membrane (BBM). The
      assay was readily applied here to rat BBM to learn if it detects DMT1 activity.
      The results demonstrate protein-mediated transport across the BBM of all tested
      ions: Mn(2+), Fe(2+), and Ni(2+). Transport into BBM vesicles (BBMV) from (b/b)
      Belgrade rats was below the detection limit. BBMV of +/b origin had substantial
      activity. The kinetic rate constant for Ni(2+) membrane transport for +/b BBMV
      was within the range for normal rabbit tissue. Vesicles from +/b basolateral
      membranes (BLM) showed similar activity to BBMV while b/b BLM vesicles (BLMV)
      lacked transport activity. Immunoblots using isoform-specific antibodies
      demonstrated that intestinal levels of b/b DMT1 were increased compared to +/b
      DMT1, reflecting iron deficiency. Immunoblots on BBMV indicated that lack of
      activity in b/b vesicles was not due to a failure of DMT1 to localize to the
      BBMV; an excess of specific isoforms was present compared to +/b BBMV or duodenal
      extracts. Immunoblots from BLMV also exhibited enrichment in DMT1 isoforms,
      despite their distinct origin. Immunofluorescent staining of thin sections of b/b
      and +/b proximal intestines confirmed that DMT1 localized similarly in mutant and
      control enterocytes and showed that DMT1 isoforms have distinct distributions
      within intestinal tissue.

PMID- 15736956
TI  - The conserved histidine 295 does not contribute to proton cotransport by the
      glutamate transporter EAAC1.
AB  - Transmembrane glutamate transport by the excitatory amino acid carrier (EAAC1) is
      coupled to the cotransport of three Na(+) ions and one proton. Previously, we
      suggested that the mechanism of H(+) cotransport involves protonation of the
      conserved glutamate residue E373. However, it was also speculated that the
      cotransported proton is shared in a H(+)-binding network, possibly involving the
      conserved histidine 295 in the sixth transmembrane domain of EAAC1. Here, we used
      site-directed mutagenesis together with pre-steady-state electrophysiological
      analysis of the mutant transporters to test the protonation state of H295 and to
      determine its involvement in proton transport by EAAC1. Our results show that
      replacement of H295 with glutamine, an amino acid residue that cannot be
      protonated, generates a fully functional transporter with transport kinetics that
      are close to those of the wild-type EAAC1. In contrast, replacement with lysine
      results in a transporter in which substrate binding and translocation are
      dramatically inhibited. Furthermore, it is demonstrated that the effect of the
      histidine 295 to lysine mutation on the glutamate affinity is caused by its
      positive charge, since wild-type-like affinity can be restored by changing the
      extracellular pH to 10.0, thus partially deprotonating H295K. Together, these
      results suggest that histidine 295 is not protonated in EAAC1 at physiological pH
      and, thus, does not contribute to H(+) cotransport. This conclusion is supported
      by data from H295C-E373C double mutant transporters which demonstrate that these
      residues cannot be linked by oxidation, indicating that H295 and E373 are not
      close in space and do not form a proton binding network. A kinetic scheme is used
      to quantify the results, which includes binding of the cotransported proton to
      E373 and binding of a modulatory, nontransported proton to the amino acid side
      chain in position 295.

PMID- 15736957
TI  - Characterization of a TET-like aminopeptidase complex from the hyperthermophilic
      archaeon Pyrococcus horikoshii.
AB  - Pyrococcus horikoshii open reading frame PH1527 encodes a 39014 Da protein that
      shares about 30% identity with endoglucanases and members of the M42 peptidase
      family. Analytical ultracentrifugation and electron microscopy studies showed
      that the purified recombinant protein forms stable, large dodecameric complexes
      with a tetrahedral shape similar to the one described for DAP, a deblocking
      aminopeptidase that was characterized in the same organism. The two related
      proteins were named PhTET1 (for DAP) and PhTET2 (for PH1527). The substrate
      specificity and the mode of action of the PhTET2 complex were studied in detail
      and compared to those of PhTET1 and other assigned M42 peptidases. When assayed
      with short chromogenic peptides, PhTET2 was found to be an aminopeptidase, with a
      clear preference for leucine as the N-terminal amino acid. However, the enzyme
      can cleave moderately long polypeptide substrates of various compositions in a
      fairly unspecific manner. The hydrolytic mechanism was found to be nonprocessive.
      The enzyme has neither carboxypeptidase nor endoproteolytic activities, and it is
      devoid of N-terminal deblocking activity. PhTET2 was inhibited in the presence of
      EDTA and bestatin, and cobalt was found to be an activating metal. The PhTET2
      protein is a highly thermostable enzyme that displays optimal activity around 100
      degrees C over a broad pH array.

PMID- 15736958
TI  - Denaturant-assisted formation of a stabilizing disulfide bridge from engineered
      cysteines in nonideal conformations.
AB  - The engineered disulfide bridge A23C/L203C in human carbonic anhydrase II,
      inserted from homology modeling of Neisseria gonorrhoeae carbonic anhydrase,
      significantly stabilizes the native state of the protein. The inserted cysteine
      residues are placed in the interior of the structure, and because of the
      conformationally restrained localization, the protein is expressed in the reduced
      state and the cysteines are not readily oxidized. However, upon exposure to low
      concentrations of denaturant (0.6 M guanidine hydrochloride), corresponding to
      the lower part of the denaturation curve for the first unfolding transition, the
      oxidation rate of correctly formed disulfide bridges was markedly increased. By
      entropy estimations it appears that the increased flexibility, induced by the
      denaturant, enables the cysteines to find each other and hence to form the
      disulfide bridge. The outlined strategy of facilitating formation of disulfide
      bonds by addition of adjusted concentrations of a denaturant should be applicable
      to other proteins in which engineered cysteine residues are located in nonideal
      conformations. Moreover, a S99C/V242C variant was constructed, in which the
      cysteine residues are located on the surface. In this mutant the disulfide bridge
      was spontaneously formed and the native state was considerably stabilized
      (midpoint concentration of unfolding was increased from 1.0 to 1.4 M guanidine
      hydrochloride).

PMID- 15736959
TI  - Purification and fluorescent labeling of the human serotonin transporter.
AB  - To establish a purification procedure for the human serotonin transporter (hSERT)
      we expressed in Sf9 insect cells an epitope-tagged version of the transporter
      containing a FLAG epitope at the N-terminus and a polyhistidine tail at the C
      terminus (FLAG-hSERT-12H). For purification, the transporter was solubilized in
      digitonin followed by nickel affinity and subsequent concanavalin A
      chromatography. Using this procedure we were able to obtain an overall
      purification of 700-fold and a yield of approximately 0.1 mg/L of cell culture.
      The purified transporter displayed pharmacological properties similar to those of
      hSERT expressed in native tissues and in transfected cell lines. Fluorescent
      labeling of the purified transporter with the thiol-reactive fluorophore
      nitrobenxoxadiazol-iodoacetamide (IANBD) and Texas Red bromoacetamide preserved
      the pharmacological profile of FLAG-hSERT-12H. Collisional quenching experiments
      revealed that the aqueous quencher iodide was able to cause marked quenching of
      the fluorescence of the IANBD labeled transporter with a K(SV) of 3.4 +/- 0.10 M(
      )(1). In a mutant transporter with five cysteines mutated (5CysKO) we observed a
      significant reduction in this quenching (K(SV) = 2.1 +/- 0.16 M(-)(1), p < 0.01).
      This reduction was most likely due to labeling of (109)Cys since mutation of this
      cysteine alone resulted in a reduction in collisional quenching that was similar
      to that observed with 5CysKO (K(SV) = 2.2 +/- 0.15 M(-)(1)). These data suggest
      that labeling of (109)Cys contributes substantially to the overall fluorescence
      of IANBD labeled FLAG-hSERT-12H. On the basis of these data we infer that
      (109)Cys is embedded in a mixed hydrophobic/hydrophilic environment at the
      external ends of transmembrane segments 1 and 2. Further use of fluorescent
      techniques on purified hSERT should prove useful in future studies aimed at
      understanding the molecular structure and function of Na(+)/Cl(-)-dependent
      neurotransmitter transporters.

PMID- 15736960
TI  - Substrate-induced conformational changes of melibiose permease from Escherichia
      coli studied by infrared difference spectroscopy.
AB  - Fourier transform infrared difference spectroscopy has been used to obtain
      information about substrate-induced structural changes of the melibiose permease
      (MelB) from Escherichia coli reconstituted into liposomes. Binding of the
      cosubstrate Na(+) gives rise to several peaks in the amide I and II regions of
      the difference spectrum Na(+).MelB minus H(+).MelB, that denote the presence of
      conformational changes in all types of secondary structures (alpha-helices, beta
      sheets, loops). In addition, peaks around 1400 and at 1740-1720 cm(-1) are
      indicative of changes in protonation/deprotonation or in environment of
      carboxylic groups. Binding of the cosubstrate Li(+) produces a difference
      spectrum that is also indicative of conformational changes, but that is at
      variance as compared to that induced by Na(+) binding. To analyze the following
      transport steps, the melibiose permease with either H(+), Na(+), or Li(+) bound
      was incubated with melibiose. The difference spectra obtained by subtracting the
      spectrum cation.MelB from the respective complex cation.melibiose.MelB were
      roughly similar among them, but different from those induced by cation binding,
      and more intense. Therefore, major conformational changes that are induced during
      melibiose binding/substrate translocation, like those denoted by intense peaks at
      1668 and 1645 cm(-)(1), are similar for the three cotransporting cations. Changes
      in the protonation state and/or in the environment of given carboxylic residues
      were also induced by melibiose-MelB interaction in the presence of cations.

PMID- 15736961
TI  - Orientation of beta-barrel proteins OmpA and FhuA in lipid membranes. Chain
      length dependence from infrared dichroism.
AB  - The outer-membrane proteins OmpA and FhuA of Escherichia coli are monomeric beta
      barrels of widely differing size. Polarized attenuated total reflection infrared
      spectroscopy has been used to determine the orientation of the beta-barrels in
      phosphatidylcholine host matrices of different lipid chain lengths. The linear
      dichroism of the amide I band from OmpA and FhuA in hydrated membranes generally
      increases with increasing chain length from diC(12:0) to diC(17:0)
      phosphatidylcholine, in both the fluid and gel phases. Measurements of the amide
      I and amide II dichroism from dry samples are used to deduce the strand tilt
      (beta = 46 degrees for OmpA and beta = 44.5 degrees for FhuA). These values are
      then used to deduce the order parameters, P(2)(cos alpha), of the beta-barrels
      from the amide I dichroic ratios of the hydrated membranes. The orientational
      ordering of the beta-barrels and their assembly in the membrane are discussed in
      terms of hydrophobic matching with the lipid chains.

PMID- 15736962
TI  - Effect of arginine loss in myelin basic protein, as occurs in its deiminated
      charge isoform, on mediation of actin polymerization and actin binding to a lipid
      membrane in vitro.
AB  - Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic
      surface of oligodendrocyte membranes and is most likely responsible for adhesion
      of these surfaces in the multilayered myelin sheath. It can also polymerize
      actin, bundle F-actin filaments, and bind actin filaments to lipid bilayers
      through electrostatic interactions. MBP consists of a number of
      posttranslationally modified isoforms of varying charge, including C8, in which
      six arginines are deiminated to the uncharged residue citrulline. The deiminated
      form decreases with development, but is increased in patients with the
      demyelinating disease multiple sclerosis. Here we investigate the effect of
      decreased net positive charge of MBP on its interaction with actin in vitro by
      comparing a recombinant murine form, rmC1, of the most highly charged unmodified
      isoform, C1, and a recombinant analogue of C8 in which six basic residues are
      converted to glutamine, rmC8. The dissociation constant of the less charged
      isoform rmC8 for actin was a little greater than that of rmC1, and rmC8 had
      somewhat reduced ability to polymerize actin and bundle F-actin filaments than
      rmC1. Moreover, rmC8 was more readily dissociated from actin by Ca(2+)-calmodulin
      than rmC1, and the ability of the deiminated isoform to bind actin to lipid
      bilayers was reduced. These results indicate that electrostatic forces are the
      primary determinant of the interaction of MBP with actin. The spin labeled side
      chains of a series of rmC1 and rmC8 variants containing single Cys substitutions
      at seven sites throughout the sequence all became motionally restricted to a
      similar degree on binding F-actin, indicating that the entire sequence is
      involved in interacting with actin filaments or is otherwise structurally
      constrained in actin bundles. Thus, this posttranslational modification of MBP,
      which occurs early in life and is increased in multiple sclerosis, attenuates the
      ability of MBP to polymerize and bundle actin, and to bind it to a negatively
      charged membrane.

PMID- 15736963
TI  - Inhibition of phosphorolysis catalyzed by HIV-1 reverse transcriptase is
      responsible for the synergy found in combinations of 3'-azido-3'-deoxythymidine
      with nonnucleoside inhibitors.
AB  - In spite of the growing attention to the combined chemotherapy in the treatment
      of AIDS, the molecular mechanisms underlying the antiviral synergy of
      combinations of reverse transcriptase (RT) inhibitors are in most cases unknown.
      Most combinations of nonnucleoside inhibitors (NNRTI) with nucleoside analogues
      synergistically inhibit HIV-1 replication in cell culture, though they fail to
      show synergy in enzymatic assays. In this work we have examined the mechanisms
      mediating the synergy in combinations of AZTTP with NNRTIs on HIV-1 RT and their
      possible relevance in antiretroviral therapy. We found that if two inhibitors
      bind either to different sites on the RT or to the same site but to different
      mechanistic forms, it is always possible to find conditions in which their
      combination results in synergistic inhibition of DNA polymerase activity. Though
      these analyses are interesting from a biochemical point of view, this kind of
      synergy is unlikely to play any role in vivo, since this positive interaction is
      lost under the conditions present in viral replication. Here we describe that the
      synergy found for combinations of NNRTI with AZT is due not to the inhibition of
      the DNA polymerase activity but to the inhibition of the RT-catalyzed
      phosphorolysis by the NNRTI. While phosphorolytical removal of the AZT-terminated
      primer has been related to the mechanism of resistance toward AZT, our data
      suggest that a basal phosphorolysis occurs even with the wild-type enzyme, and
      that the inhibition of this activity could explain the synergy found in antiviral
      assays.

PMID- 15736964
TI  - Role of activation function domain-1, DNA binding, and coactivator GRIP1 in the
      expression of partial agonist activity of glucocorticoid receptor-antagonist
      complexes.
AB  - The determinants of the partial agonist activity of most antisteroids complexed
      with steroid receptors are not well understood. We now examine the role of the N
      terminal half of the glucocorticoid receptor (GR) including the activation domain
      (AF-1), the DNA binding site sequence, receptor contact with DNA, and coactivator
      binding on the expression of partial agonist activity in two cell lines for GRs
      bound by five antiglucocorticoids: dexamethasone mesylate (Dex-Mes),
      dexamethasone oxetanone (Dex-Ox), progesterone (Prog), deoxycorticosterone (DOC),
      and RU486. Using truncated GRs, we find that the N-terminal half of GR and the AF
      1 domain are dispensable for the partial agonist activity of antiglucocorticoids.
      This contrasts with the AF-1 domain being required for the partial agonist
      activity of antisteroids with most steroid receptors. DNA sequence (MMTV vs a
      simple GRE enhancer) and cell-specific factors (CV-1 vs Cos-7) exert minor
      effects on the level of partial agonist activity. Small activity differences for
      some complexes of GAL4/GR chimeras with GR- vs GAL-responsive reporters suggest a
      contribution of DNA-induced conformational changes. A role for steroid-regulated
      coactivator binding to GRs is compatible with the progressively smaller increase
      in partial agonist activity of Dex-Mes > Prog > RU486 with added GRIP1 in CV-1
      cells. This hypothesis is consistent with titration experiments, where low
      concentrations of GRIP1 more effectively increase the partial agonist activity of
      Dex-Mes than Prog complexes. Furthermore, ligand-dependent GRIP1 binding to DNA
      bound GR complexes decreases in the order of Dex > Dex-Mes > Prog > RU486. Thus,
      the partial agonist activity of a given GR-steroid complex in CV-1 cells
      correlates with its cell-free binding of GRIP1. The ability to modify the levels
      of partial agonist activity through changes in steroid structure, DNA sequence,
      specific DNA-induced conformational changes, and coactivator binding suggests
      that useful variations in endocrine therapies may be possible by the judicious
      selection of these parameters to afford gene and tissue selective results.

PMID- 15736966
TI  - A flavo-diiron protein from Desulfovibrio vulgaris with oxidase and nitric oxide
      reductase activities. Evidence for an in vivo nitric oxide scavenging function.
AB  - A few members of a widespread class of bacterial and archaeal flavo-diiron
      proteins, dubbed FprAs, have been shown to function as either oxidases (dioxygen
      reductases) or scavenging nitric oxide reductases, but the questions of which of
      these functions dominates in vivo for a given FprA and whether all FprAs function
      as oxidases or nitric oxide reductases remain to be clarified. To address these
      questions, an FprA has been characterized from the anaerobic sulfate-reducing
      bacterium Desulfovibrio vulgaris. The gene encoding this D. vulgaris FprA lies
      downstream of an operon encoding superoxide reductase and rubredoxin, consistent
      with an O(2)-scavenging oxidase function for this FprA. The recombinant D.
      vulgaris FprA can indeed serve as the terminal component of an NADH oxidase.
      However, this oxidase turnover results in irreversible inactivation of the
      enzyme. On the other hand, the recombinant D. vulgaris FprA shows robust
      anaerobic nitric oxide reductase activity in vitro and also protects a nitric
      oxide-sensitive Escherichia coli strain against exposure to exogenous nitric
      oxide. It is, therefore, proposed that this D. vulgaris FprA functions as a
      scavenging nitric oxide reductase in vivo and that this activity protects D.
      vulgaris against anaerobic exposure to nitric oxide. The location of a gene
      encoding a second FprA homologue in the D. vulgaris genome also suggests its
      involvement in nitrogen oxide metabolism.

PMID- 15736965
TI  - Characterization of the membrane domain subunit NuoJ (ND6) of the NADH-quinone
      oxidoreductase from Escherichia coli by chromosomal DNA manipulation.
AB  - The ND6 subunit is one of seven mitochondrial DNA-encoded subunits of the proton
      translocating NADH-quinone oxidoreductase (complex I). Physiological importance
      of the ND6 subunit is becoming increasingly apparent because a number of
      mutations leading to amino acid changes in this subunit have been found to be
      associated with known mitochondrial diseases. Using the Escherichia coli enzyme
      (NDH-1), we have investigated the NuoJ subunit (the E. coli counterpart of ND6)
      by employing a chromosomal DNA manipulation technique. A series of point
      mutations was constructed directly on the nuoJ gene in the chromosome targeting
      at highly conserved residues. Analyses with blue-native gel electrophoresis and
      immunological methods revealed that, in all point mutants, the assembly of NDH-1
      was normal and that the deamino-NADH-K(3)Fe(CN)(6) reductase activity of the
      membrane was essentially the same as that of the wild-type. However, energy
      coupled NDH-1 activities were affected to varied extents. Among them, mutants of
      the Val-65 residue that is located in the most conserved transmembrane segment
      significantly lost the coupled electron-transfer activities and exhibited
      diminished membrane potential and proton translocation. This may suggest that Val
      65 or the area around it is important for energy transduction of the coupling
      site 1. Together with the results on mutations related to human diseases,
      possible functional roles of the NuoJ subunit have been discussed.

PMID- 15736967
TI  - The interaction of human tryptase-beta with small molecule inhibitors provides
      new insights into the unusual functional instability and quaternary structure of
      the protease.
AB  - Human tryptase-beta (HTbeta) is a serine protease with an atypical tetrameric
      structure and an unusual dependence on heparin binding or high salt for
      functional and structural stability. In the absence of heparin and at
      physiological salt, pH, and temperature, HTbeta rapidly loses activity by a
      reversible process that we have called spontaneous inactivation. The role of
      tetramer dissociation in this process is controversial. Using small irreversible
      or competitive inhibitors of HTbeta as stabilizing ligands, we were able to
      examine tetramer stability under inactivating (decay) conditions in the absence
      of heparin and to define further the process of spontaneous inactivation. Size
      exclusion chromatography showed that interaction with inhibitors stabilized the
      tetramer. Using sedimentation equilibrium, spontaneously inactivated HTbeta (si
      HTbeta) was shown to be a destabilized tetramer that dissociates upon dilution
      and which in the presence of a competitive inhibitor re-formed a stable tetramer.
      Addition of inhibitors to si-HTbeta rescued catalytic activity as was shown after
      inhibitor displacement. At high concentrations of si-HTbeta (4-5 microM), the
      binding of inhibitor alone provided sufficient free energy for complete
      reactivation and tetramer stabilization, whereas at low si-HTbeta concentration
      (0.1 microM) where the destabilized tetramer would be mostly dissociated,
      reactivation required more free energy which was provided by the binding of both
      an inhibitor and heparin. The results demonstrate that HTbeta is a tetramer in
      the absence of heparin and that tetramer dissociation is a consequence of and not
      a prerequisite for inactivation. Heparin binding likely stabilizes the tetramer
      by favoring a functionally active conformation with stable intersubunit contacts,
      rather than by simply cross-linking active monomers.

PMID- 15736968
TI  - Structural role of glycine in amyloid fibrils formed from transmembrane alpha
      helices.
AB  - Amyloid fibrils associated with diseases such as Alzheimer's are often derived
      from the transmembrane helices of membrane proteins. It is known that the fibrils
      have a cross-beta-sheet structure where main chain hydrogen bonding occurs
      between beta-strands in the direction of the fibril axis. However, the structural
      basis for how the membrane-spanning helix is converted into a beta-sheet or how
      protofibrils associate into fibrils is not known. Here, we use a model peptide
      corresponding to a portion of the single transmembrane helix of glycophorin A to
      investigate the structural role of glycine in amyloid-like fibrils formed from
      transmembrane helices. Glycophorin A contains a GxxxG motif that is found in many
      transmembrane sequences including that of the amyloid precursor protein and prion
      protein. We propose that glycine, which mediates helix interactions in membrane
      proteins, also provides key packing motifs when it occurs in beta-sheets. We show
      that glycines in the glycophorin A transmembrane helix promote extended beta
      strand formation when the helix partitions into aqueous environments and
      stabilize the packing of beta-sheets in the formation of amyloid-like fibrils. We
      demonstrate that fibrillization can be disrupted with a new class of inhibitors
      that target the molecular grooves created by glycine.

PMID- 15736969
TI  - Transbilayer complementarity of phospholipids in cholesterol-rich membranes.
AB  - Lipid-lipid interactions across cholesterol-rich phospholipid bilayers were
      investigated by measuring nearest-neighbor preferences of exchangeable
      phospholipids derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine
      (DMPE) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), in the
      presence of nonexchangeable dimers (i.e., templates) made from DMPE or DSPE. When
      homotemplates were present, a significant preference for homophospholipid
      association was observed. In contrast, when the corresponding heterotemplate was
      present, heterodimer formation was favored. These results support a model in
      which the longer phospholipid in one monolayer preferentially associates with the
      shorter one in the adjoining monolayer. In the absence of cholesterol,
      transbilayer complementarity was also observed but to a lesser degree.
      Transbilayer complementarity of phospholipids is likely to play an important role
      in stabilizing biological membranes and in promoting a compositional
      interdependence of their two lipid leaflets.

PMID- 15736970
TI  - Composite organization of the cobalamin binding and cubilin recognition sites of
      intrinsic factor.
AB  - Intrinsic factor (IF(50)) is a cobalamin (Cbl)-transporting protein of 50 kDa,
      which can be cleaved into two fragments: the 30 kDa N-terminal peptide IF(30) and
      the 20 kDa C-terminal glycopeptide IF(20). Experiments on binding of Cbl to
      IF(30), IF(20), and IF(50) revealed comparable association rate constants
      (k(+)(Cbl) = 4 x 10(6), 14 x 10(6), and 26 x 10(6) M(-1) s(-1), respectively),
      but the equilibrium dissociation constants were essentially different (K(Cbl) =
      200 microM, 0.2 microM, and <or=1 pM, respectively). The smaller fragment,
      IF(20), had unexpectedly high affinity for Cbl; however, efficient retention of
      the ligand required the presence of both fragments. Detailed schemes of the
      interaction of Cbl with IF(50) and with IF(30) and IF(20) are presented, where
      the sequential attachment of Cbl to the IF(20) and IF(30) domains plays the key
      role in recognition and retention of the ligand. Each isolated fragment of IF was
      tested for the binding to the specific receptor cubilin in the presence or
      absence of Cbl. Neither apo nor holo forms of IF(20) and IF(30) were recognized
      by the receptor. When two fragments were mixed and incubated with Cbl, they
      associated into a stable complex, IF(30+20).Cbl, which bound to cubilin as well
      as the noncleaved IF(50).Cbl complex. We suggest that formation of the cubilin
      recognition site on IF is caused by assembly of two distant domains, which allows
      the saturated protein to be recognized by the receptor. The obtained parameters
      for ligand and receptor binding indicate that both full-length IF(50) and the
      fragments may be involved in Cbl assimilation.

PMID- 15736972
TI  - A catalytic triad is responsible for acid-base chemistry in the Ascaris suum NAD
      malic enzyme.
AB  - The pH dependence of kinetic parameters of several active site mutants of the
      Ascaris suum NAD-malic enzyme was investigated to determine the role of amino
      acid residues likely involved in catalysis on the basis of three-dimensional
      structures of malic enzyme. Lysine 199 is positioned to act as the general base
      that accepts a proton from the 2-hydroxyl of malate during the hydride transfer
      step. The pH dependence of V/K(malate) for the K199R mutant enzyme reveals a pK
      of 5.3 for an enzymatic group required to be unprotonated for activity and a
      second pK of 6.3 that leads to a 10-fold loss in activity above the pK of 6.3 to
      a new constant value up to pH 10. The V profile for K199R is pH independent from
      pH 5.5 to pH 10 and decreases below a pK of 4.9. Tyrosine 126 is positioned to
      act as the general acid that donates a proton to the enolpyruvate intermediate to
      form pyruvate. The pH dependence of V/K(malate) for the Y126F mutant is
      qualitatively similar to K199R, with a requirement for a group to be unprotonated
      for activity with a pK of 5.6 and a partial activity loss of about 3-fold above a
      pK of 6.7 to a new constant value. The Y126F mutant enzyme is about 60000-fold
      less active than the wild-type enzyme. In contrast to K199R, the V rate profile
      for Y126F also shows a partial activity loss above pH 6.6. The wild-type pH
      profiles were reinvestigated in light of the discovery of the partial activity
      change for the mutant enzymes. The wild-type V/K(malate) pH-rate profile exhibits
      the requirement for a group to be unprotonated for catalysis with a pK of 5.6 and
      also shows the partial activity loss above a pK of 6.4. The wild-type V pH-rate
      profile decreases below a pK of 5.2 and is pH independent from pH 5.5 to pH 10.
      Aspartate 294 is within hydrogen-bonding distance to K199 in the open and closed
      forms of malic enzyme. D294A is about 13000-fold less active than the wild-type
      enzyme, and the pH-rate profile for V/K(malate) indicates the mutant is only
      active above pH 9. The data suggest that the pK present at about pH 5.6 in all of
      the pH profiles represents D294, and during catalysis D294 accepts a proton from
      K199 to allow K199 to act as a general base in the reaction. The pK for the
      general acid in the reaction is not observed, consistent with rapid
      tautomerization of enolpyruvate. No other ionizable group in the active site is
      likely responsible for the partial activity change observed in the pH profiles,
      and thus the group responsible is probably remote from the active site and the
      effect on activity is transmitted through the protein by a conformational change.

PMID- 15736971
TI  - The factor IXa heparin-binding exosite is a cofactor interactive site: mechanism
      for antithrombin-independent inhibition of intrinsic tenase by heparin.
AB  - Therapeutic heparin concentrations selectively inhibit the intrinsic tenase
      complex in an antithrombin-independent manner. To define the molecular target and
      mechanism for this inhibition, recombinant human factor IXa with alanine
      substituted for solvent-exposed basic residues (H92, R170, R233, K241) in the
      protease domain was characterized with regard to enzymatic activity, heparin
      affinity, and inhibition by low molecular weight heparin (LMWH). These mutations
      only had modest effects on chromogenic substrate hydrolysis and the kinetics of
      factor X activation by factor IXa. Likewise, factor IXa H92A and K241A showed
      factor IXa-factor VIIIa affinity similar to factor IXa wild type (WT). In
      contrast, factor IXa R170A demonstrated a 4-fold increase in apparent factor IXa
      factor VIIIa affinity and dramatically increased coagulant activity relative to
      factor IXa WT. Factor IXa R233A demonstrated a 2.5-fold decrease in cofactor
      affinity and reduced ability to stabilize cofactor half-life relative to wild
      type, suggesting that interaction with the factor VIIIa A2 domain was disrupted.
      Markedly (R233A) or moderately (H92A, R170A, K241A) reduced binding to
      immobilized LMWH was observed for the mutant proteases. Solution competition
      demonstrated that the EC(50) for LMWH was increased less than 2-fold for factor
      IXa H92A and K241A but over 3.5-fold for factor IXa R170A, indicating that
      relative heparin affinity was WT > H92A/K241A > R170A >> R233A. Kinetic analysis
      of intrinsic tenase inhibition demonstrated that relative affinity for LMWH was
      WT > K241A > H92A > R170A >> R233A, correlating with heparin affinity. Thus, LMWH
      inhibits intrinsic tenase by interacting with the heparin-binding exosite in the
      factor IXa protease domain, which disrupts interaction with the factor VIIIa A2
      domain.

PMID- 15736973
TI  - Spontaneous chemical reversion of an active site mutation: deamidation of an
      asparagine residue replacing the catalytic aspartic acid of glutamate
      dehydrogenase.
AB  - A mutant (D165N) of clostridial glutamate dehydrogenase (GDH) in which the
      catalytic Asp is replaced by Asn surprisingly showed a residual 2% of wild-type
      activity when purified after expression in Escherichia coli at 37 degrees C. This
      low-level activity also displayed Michaelis constants for substrates that were
      remarkably similar to those of the wild-type enzyme. Expression at 8 degrees C
      gave a mutant enzyme preparation 1000 times less active than the first
      preparation, but progressively, over 2 weeks' incubation at 37 degrees C in
      sealed vials, this enzyme regained 90% of the specific activity of wild type.
      This suggested that the mutant might undergo spontaneous deamidation. Mass
      spectrometric analysis of tryptic peptides derived from D165N samples treated in
      various ways showed (i) that the Asn is in place in D165N GDH freshly prepared at
      8 degrees C; (ii) that there is a time-dependent reversion of this Asn to Asp
      over the 2-week incubation period; (iii) that detectable deamidation of other Asn
      residues, in Asn-Gly sequences, mainly occurred in sample workup rather than
      during the 2-week incubation; (iv) that there is no significant deamidation of
      other randomly chosen Asn residues in this mutant over the same period; and (v)
      that when the protein is denatured before incubation, no deamidation at Asn-165
      is detectable. It appears that this deamidation depends on the residual catalytic
      machinery of the mutated GDH active site. A literature search indicates that this
      finding is not unique and that Asn may not be a suitable mutational replacement
      in the assessment of putative catalytic Asp residues by site-directed
      mutagenesis.

PMID- 15736974
TI  - Diversity of human insulin-like growth factor (IGF) binding protein-2 fragments
      in plasma: primary structure, IGF-binding properties, and disulfide bonding
      pattern.
AB  - The insulin-like growth factor binding proteins (IGFBPs) play a major role in the
      regulation of the effects and the bioavailability of the insulin-like growth
      factors (IGFs). IGFs are released from IGFBP-IGF complexes by proteolysis of
      IGFBPs generating fragments with reduced ligand-binding properties. To identify
      naturally occurring fragments of IGFBP-2, a peptide library generated from human
      hemofiltrate was immunologically screened. Purification of immunoreactive IGFBP-2
      fragments was performed by consecutive chromatographic steps. A total of 18
      different IGFBP-2 fragments was isolated and characterized. The peptides
      exhibited different N-terminal amino acid residues that were located in the
      variable midregion of IGFBP-2. Four major cleavage sites were determined to be
      between Tyr103 and Gly104, Leu152 and Ala153, Arg156 and Glu157, and Gln165 and
      Met166. The resulting fragments were further processed by amino and/or carboxy
      peptidases and comprised 37-185 amino acid residues. Ligand blotting, solution
      binding assays, and BIAcore analyses revealed that all tested fragments retained
      low IGF-binding capacity. The most abundant fragment IGFBP-2 (167-279) showed 10%
      of IGF-II binding compared to recombinant human (rh)IGFBP-2. Furthermore, the
      disulfide bonding pattern of the C-terminal domain of rhIGFBP-2 was defined,
      indicating linkages between cysteine residues 191-225, 236-247, and 249-270. This
      study provides the most comprehensive molecular characterization of human IGFBP-2
      fragments formed in vivo, exhibiting both residual IGF-binding capacities and the
      integrin-binding sequence.

PMID- 15736975
TI  - Perceptual and neural olfactory similarity in honeybees.
AB  - The question of whether or not neural activity patterns recorded in the olfactory
      centres of the brain correspond to olfactory perceptual measures remains
      unanswered. To address this question, we studied olfaction in honeybees Apis
      mellifera using the olfactory conditioning of the proboscis extension response.
      We conditioned bees to odours and tested generalisation responses to different
      odours. Sixteen odours were used, which varied both in their functional group
      (primary and secondary alcohols, aldehydes and ketones) and in their carbon-chain
      length (from six to nine carbons). The results obtained by presentation of a
      total of 16 x 16 odour pairs show that (i) all odorants presented could be
      learned, although acquisition was lower for short-chain ketones; (ii)
      generalisation varied depending both on the functional group and the carbon-chain
      length of odours trained; higher generalisation was found between long-chain than
      between short-chain molecules and between groups such as primary and secondary
      alcohols; (iii) for some odour pairs, cross-generalisation between odorants was
      asymmetric; (iv) a putative olfactory space could be defined for the honeybee
      with functional group and carbon-chain length as inner dimensions; (v) perceptual
      distances in such a space correlate well with physiological distances determined
      from optophysiological recordings of antennal lobe activity. We conclude that
      functional group and carbon-chain length are inner dimensions of the honeybee
      olfactory space and that neural activity in the antennal lobe reflects the
      perceptual quality of odours.

PMID- 15736976
TI  - Recombination difference between sexes: a role for haploid selection.
AB  - Why the autosomal recombination rate differs between female and male meiosis in
      most species has been a genetic enigma since the early study of meiosis. Some
      hypotheses have been put forward to explain this widespread phenomenon and, up to
      now, only one fact has emerged clearly: In species in which meiosis is achiasmate
      in one sex, it is the heterogametic one. This pattern, known as the Haldane
      Huxley rule, is thought to be a side effect, on autosomes, of the suppression of
      recombination between the sex chromosomes. However, this rule does not hold for
      heterochiasmate species (i.e., species in which recombination is present in both
      sexes but varies quantitatively between sexes) and does not apply to species
      lacking sex chromosomes, such as hermaphroditic plants. In this paper, we show
      that in plants, heterochiasmy is due to a male-female difference in gametic
      selection and is not influenced by the presence of heteromorphic sex chromosomes.
      This finding provides strong empirical support in favour of a population genetic
      explanation for the evolution of heterochiasmy and, more broadly, for the
      evolution of sex and recombination.

PMID- 15736977
TI  - Engineering gene networks to emulate Drosophila embryonic pattern formation.
AB  - Pattern formation is essential in the development of higher eukaryotes. For
      example, in the Drosophila embryo, maternal morphogen gradients establish gap
      gene expression domain patterning along the anterior-posterior axis, through
      linkage with an elaborate gene network. To understand the evolution and behaviour
      of such systems better, it is important to establish the minimal determinants
      required for patterning. We have therefore engineered artificial transcription
      translation networks that generate simple patterns, crudely analogous to the
      Drosophila gap gene system. The Drosophila syncytium was modelled using DNA
      coated paramagnetic beads fixed by magnets in an artificial chamber, forming a
      gene expression network. Transient expression domain patterns were generated
      using various levels of network connectivity. Generally, adding more
      transcription repression interactions increased the "sharpness" of the pattern
      while reducing overall expression levels. An accompanying computer model for our
      system allowed us to search for parameter sets compatible with patterning. While
      it is clear that the Drosophila embryo is far more complex than our simplified
      model, several features of interest emerge. For example, the model suggests that
      simple diffusion may be too rapid for Drosophila-scale patterning, implying that
      sublocalisation, or "trapping," is required. Second, we find that for pattern
      formation to occur under the conditions of our in vitro reaction-diffusion
      system, the activator molecules must propagate faster than the inhibitors. Third,
      adding controlled protease degradation to the system stabilizes pattern formation
      over time. We have reconstituted transcriptional pattern formation from purified
      substances, including phage RNA polymerases, ribonucleotides, and an eukaryotic
      translation extract. We anticipate that the system described here will be
      generally applicable to the study of any biological network with a spatial
      component.

PMID- 15736978
TI  - Recent origin and cultural reversion of a hunter-gatherer group.
AB  - Contemporary hunter-gatherer groups are often thought to serve as models of an
      ancient lifestyle that was typical of human populations prior to the development
      of agriculture. Patterns of genetic variation in hunter-gatherer groups such as
      the Kung and African Pygmies are consistent with this view, as they exhibit low
      genetic diversity coupled with high frequencies of divergent mtDNA types not
      found in surrounding agricultural groups, suggesting long-term isolation and
      small population sizes. We report here genetic evidence concerning the origins of
      the Mlabri, an enigmatic hunter-gatherer group from northern Thailand. The Mlabri
      have no mtDNA diversity, and the genetic diversity at Y-chromosome and autosomal
      loci are also extraordinarily reduced in the Mlabri. Genetic, linguistic, and
      cultural data all suggest that the Mlabri were recently founded, 500-800 y ago,
      from a very small number of individuals. Moreover, the Mlabri appear to have
      originated from an agricultural group and then adopted a hunting-gathering
      subsistence mode. This example of cultural reversion from agriculture to a
      hunting-gathering lifestyle indicates that contemporary hunter-gatherer groups do
      not necessarily reflect a pre-agricultural lifestyle.

PMID- 15736979
TI  - Modeling the mutualistic interactions between tubeworms and microbial consortia.
AB  - The deep-sea vestimentiferan tubeworm Lamellibrachia luymesi forms large
      aggregations at hydrocarbon seeps in the Gulf of Mexico that may persist for over
      250 y. Here, we present the results of a diagenetic model in which tubeworm
      aggregation persistence is achieved through augmentation of the supply of sulfate
      to hydrocarbon seep sediments. In the model, L. luymesi releases the sulfate
      generated by its internal, chemoautotrophic, sulfide-oxidizing symbionts through
      posterior root-like extensions of its body. The sulfate fuels sulfate reduction,
      commonly coupled to anaerobic methane oxidation and hydrocarbon degradation by
      bacterial-archaeal consortia. If sulfate is released by the tubeworms, sulfide
      generation mainly by hydrocarbon degradation is sufficient to support moderate
      sized aggregations of L. luymesi for hundreds of years. The results of this model
      expand our concept of the potential benefits derived from complex interspecific
      relationships, in this case involving members of all three domains of life.

PMID- 15736982
TI  - Selection on Sex Cells Favors a Recombination Gender Gap.

PMID- 15736980
TI  - Location coding by opponent neural populations in the auditory cortex.
AB  - Although the auditory cortex plays a necessary role in sound localization,
      physiological investigations in the cortex reveal inhomogeneous sampling of
      auditory space that is difficult to reconcile with localization behavior under
      the assumption of local spatial coding. Most neurons respond maximally to sounds
      located far to the left or right side, with few neurons tuned to the frontal
      midline. Paradoxically, psychophysical studies show optimal spatial acuity across
      the frontal midline. In this paper, we revisit the problem of inhomogeneous
      spatial sampling in three fields of cat auditory cortex. In each field, we
      confirm that neural responses tend to be greatest for lateral positions, but show
      the greatest modulation for near-midline source locations. Moreover,
      identification of source locations based on cortical responses shows sharp
      discrimination of left from right but relatively inaccurate discrimination of
      locations within each half of space. Motivated by these findings, we explore an
      opponent-process theory in which sound-source locations are represented by
      differences in the activity of two broadly tuned channels formed by contra- and
      ipsilaterally preferring neurons. Finally, we demonstrate a simple model, based
      on spike-count differences across cortical populations, that provides bias-free,
      level-invariant localization-and thus also a solution to the "binding problem" of
      associating spatial information with other nonspatial attributes of sounds.

PMID- 15736983
TI  - How the Brain Signals a Sound Source.

PMID- 15736984
TI  - Engineering Gene Networks to Probe Embryonic Pattern Formation in Flies.

PMID- 15736985
TI  - Tubeworm May Live Longer by Cycling Its Sulfur Downward.

PMID- 15736981
TI  - Grasping the intentions of others with one's own mirror neuron system.
AB  - Understanding the intentions of others while watching their actions is a
      fundamental building block of social behavior. The neural and functional
      mechanisms underlying this ability are still poorly understood. To investigate
      these mechanisms we used functional magnetic resonance imaging. Twenty-three
      subjects watched three kinds of stimuli: grasping hand actions without a context,
      context only (scenes containing objects), and grasping hand actions performed in
      two different contexts. In the latter condition the context suggested the
      intention associated with the grasping action (either drinking or cleaning).
      Actions embedded in contexts, compared with the other two conditions, yielded a
      significant signal increase in the posterior part of the inferior frontal gyrus
      and the adjacent sector of the ventral premotor cortex where hand actions are
      represented. Thus, premotor mirror neuron areas-areas active during the execution
      and the observation of an action-previously thought to be involved only in action
      recognition are actually also involved in understanding the intentions of others.
      To ascribe an intention is to infer a forthcoming new goal, and this is an
      operation that the motor system does automatically.

PMID- 15736987
TI  - An Evolutionary Road Less Traveled: From Farming to Hunting and Gathering.

PMID- 15736986
TI  - Predicting the Future: Mirror Neurons Reflect the Intentions of Others.

PMID- 15736988
TI  - Cracking the Olfactory Code.

PMID- 15736989
TI  - EGFR inhibition in non-small cell lung cancer: resistance, once again, rears its
      ugly head.

PMID- 15736990
TI  - Teaching health workers malaria diagnosis.

PMID- 15736991
TI  - The courage to change the rules: a proposal for an essential health R&D treaty.

PMID- 15736992
TI  - Can blood gene expression predict which patients with multiple sclerosis will
      respond to interferon?

PMID- 15736993
TI  - Asthma severity and prevalence: an ongoing interaction between exposure, hygiene,
      and lifestyle.

PMID- 15736994
TI  - Individual level injection history: a lack of association with HIV incidence in
      rural Zimbabwe.
AB  - BACKGROUND: It has recently been argued that unsafe medical injections are a
      major transmission route of HIV infection in the generalised epidemics of sub
      Saharan Africa. METHODS AND FINDINGS: We have analysed the pattern of injections
      in relation to HIV incidence in a population cohort in Manicaland in a rural area
      of Zimbabwe. In Poisson regression models, injections were not found to be
      associated with HIV in males (rate ratio = 0.33; 95% confidence interval: 0.07 to
      1.46) or females (rate ratio = 1.04; 95% confidence interval: 0.59 to 1.85).
      CONCLUSION: It is important that unsafe medical injections can be confidently
      excluded as a major source of HIV infection. In rural Zimbabwe the evidence is
      that they can.

PMID- 15736995
TI  - Use of procalcitonin and C-reactive protein to evaluate vaccine efficacy against
      pneumonia.
AB  - BACKGROUND: Pneumonia remains the leading cause of death in young children. The
      poor specificity of chest radiographs (CXRs) to diagnose pneumococcal pneumonia
      may underestimate the efficacy of pneumococcal conjugate vaccine in preventing
      pneumococcal pneumonia. METHODS AND FINDINGS: The efficacy of nine-valent
      pneumococcal conjugate vaccine among children not infected with HIV (21%; 95%
      confidence interval, 1%-37%) increased when CXR-confirmed pneumonia was
      associated with serum C-reactive protein of 120 mg/l (12 mg/dl) or more and
      procalcitonin of 5.0 ng/ml or more (64%; 95% confidence interval, 23%-83%).
      Similar results were observed in children infected with HIV. CONCLUSION: C
      reactive protein and procalcitonin improve the specificity of CXR to diagnose
      pneumococcal pneumonia and may be useful for the future evaluation of the
      effectiveness of pneumococcal conjugate vaccine in preventing pneumococcal
      pneumonia.

PMID- 15736996
TI  - Case-based study: from prediabetes to complications--opportunities for
      prevention.

PMID- 15736997
TI  - A person-centred approach to communicating risk.

PMID- 15736998
TI  - Communicating with patients about harms and risks.

PMID- 15736999
TI  - SARS transmission pattern in Singapore reassessed by viral sequence variation
      analysis.
AB  - BACKGROUND: Epidemiological investigations of infectious disease are mainly
      dependent on indirect contact information and only occasionally assisted by
      characterization of pathogen sequence variation from clinical isolates. Direct
      sequence analysis of the pathogen, particularly at a population level, is
      generally thought to be too cumbersome, technically difficult, and expensive. We
      present here a novel application of mass spectrometry (MS)-based technology in
      characterizing viral sequence variations that overcomes these problems, and we
      apply it retrospectively to the severe acute respiratory syndrome (SARS) outbreak
      in Singapore. METHODS AND FINDINGS: The success rate of the MS-based analysis for
      detecting SARS coronavirus (SARS-CoV) sequence variations was determined to be
      95% with 75 copies of viral RNA per reaction, which is sufficient to directly
      analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolates from
      the different stages of the Singapore outbreak identified nine sequence
      variations that could define the molecular relationship between them and pointed
      to a new, previously unidentified, primary route of introduction of SARS-CoV into
      the Singapore population. Our direct determination of viral sequence variation
      from a clinical sample also clarified an unresolved epidemiological link
      regarding the acquisition of SARS in a German patient. We were also able to
      detect heterogeneous viral sequences in primary lung tissues, suggesting a
      possible coevolution of quasispecies of virus within a single host. CONCLUSION:
      This study has further demonstrated the importance of improving clinical and
      epidemiological studies of pathogen transmission through the use of genetic
      analysis and has revealed the MS-based analysis to be a sensitive and accurate
      method for characterizing SARS-CoV genetic variations in clinical samples. We
      suggest that this approach should be used routinely during outbreaks of a wide
      variety of agents, in order to allow the most effective control.

PMID- 15737000
TI  - Can routine commercial cord blood banking be scientifically and ethically
      justified?
AB  - BACKGROUND TO THE DEBATE: Umbilical cord blood--the blood that remains in the
      placenta after birth--can be collected and stored frozen for years. A well
      accepted use of cord blood is as an alternative to bone marrow as a source of
      hematopoietic stem cells for allogeneic transplantation to siblings or to
      unrelated recipients; women can donate cord blood for unrelated recipients to
      public banks. However, private banks are now open that offer expectant parents
      the option to pay a fee for the chance to store cord blood for possible future
      use by that same child (autologous transplantation).

PMID- 15737001
TI  - Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial
      apoptosis in diabetic nephropathy.
AB  - BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and
      type 2 diabetes mellitus and the most common cause of kidney failure. While DNP
      manifests with albuminuria and diabetic glomerulopathy, its progression
      correlates best with tubular epithelial degeneration (TED) and interstitial
      fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.
      METHODS AND FINDINGS: We found that expression of scavenger receptor CD36
      coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED
      specifically in human DNP. High glucose stimulated cell surface expression of
      CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC
      apoptosis induced by glycated albumins (AGE-BSA and CML-BSA) and free fatty acid
      palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK
      and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic
      mice with diabetic glomerulopathy was associated with normal tubular epithelium
      and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant
      to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs
      conferred susceptibility to AGE-BSA-induced apoptosis. CONCLUSION: Our findings
      suggest a novel role for CD36 as an essential mediator of proximal tubular
      apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs,
      and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced
      PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of
      progression in DNP.

PMID- 15737002
TI  - Free community science and the free development of science.

PMID- 15737003
TI  - Unregistered trials are unethical.

PMID- 15737004
TI  - Open access to trials register.

PMID- 15737010
TI  - Why bigger is not yet better: the problems with huge datasets.

PMID- 15737005
TI  - Designing equitable antiretroviral allocation strategies in resource-constrained
      countries.
AB  - BACKGROUND: Recently, a global commitment has been made to expand access to
      antiretrovirals (ARVs) in the developing world. However, in many resource
      constrained countries the number of individuals infected with HIV in need of
      treatment will far exceed the supply of ARVs, and only a limited number of health
      care facilities (HCFs) will be available for ARV distribution. Deciding how to
      allocate the limited supply of ARVs among HCFs will be extremely difficult.
      Resource allocation decisions can be made on the basis of many epidemiological,
      ethical, or preferential treatment priority criteria. METHODS AND FINDINGS: Here
      we use operations research techniques, and we show how to determine the optimal
      strategy for allocating ARVs among HCFs in order to satisfy the equitable
      criterion that each individual infected with HIV has an equal chance of receiving
      ARVs. We present a novel spatial mathematical model that includes heterogeneity
      in treatment accessibility. We show how to use our theoretical framework, in
      conjunction with an equity objective function, to determine an optimal equitable
      allocation strategy (OEAS) for ARVs in resource-constrained regions. Our equity
      objective function enables us to apply the egalitarian principle of equity with
      respect to access to health care. We use data from the detailed ARV rollout plan
      designed by the government of South Africa to determine an OEAS for the province
      of KwaZulu-Natal. We determine the OEAS for KwaZulu-Natal, and we then compare
      this OEAS with two other ARV allocation strategies: (i) allocating ARVs only to
      Durban (the largest urban city in KwaZulu-Natal province) and (ii) allocating
      ARVs equally to all available HCFs. In addition, we compare the OEAS to the
      current allocation plan of the South African government (which is based upon
      allocating ARVs to 17 HCFs). We show that our OEAS significantly improves equity
      in treatment accessibility in comparison with these three ARV allocation
      strategies. We also quantify how the size of the catchment region surrounding
      each HCF, and the number of HCFs utilized for ARV distribution, alters the OEAS
      and the probability of achieving equity in treatment accessibility. We calculate
      that in order to achieve the greatest degree of treatment equity for individuals
      with HIV in KwaZulu-Natal, the ARVs should be allocated to 54 HCFs and each HCF
      should serve a catchment region of 40 to 60 km. CONCLUSION: Our OEAS would
      substantially improve equality in treatment accessibility in comparison with
      other allocation strategies. Furthermore, our OEAS is extremely different from
      the currently planned strategy. We suggest that our novel methodology be used to
      design optimal ARV allocation strategies for resource-constrained countries.

PMID- 15737013
TI  - Designing an equitable strategy for allocating antiretroviral treatments.

PMID- 15737017
TI  - Differential trends in the intestinal and diffuse types of gastric carcinoma.

PMID- 15737014
TI  - Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is
      associated with a second mutation in the EGFR kinase domain.
AB  - BACKGROUND: Lung adenocarcinomas from patients who respond to the tyrosine kinase
      inhibitors gefitinib (Iressa) or erlotinib (Tarceva) usually harbor somatic gain
      of-function mutations in exons encoding the kinase domain of the epidermal growth
      factor receptor (EGFR). Despite initial responses, patients eventually progress
      by unknown mechanisms of "acquired" resistance. METHODS AND FINDINGS: We show
      that in two of five patients with acquired resistance to gefitinib or erlotinib,
      progressing tumors contain, in addition to a primary drug-sensitive mutation in
      EGFR, a secondary mutation in exon 20, which leads to substitution of methionine
      for threonine at position 790 (T790M) in the kinase domain. Tumor cells from a
      sixth patient with a drug-sensitive EGFR mutation whose tumor progressed on
      adjuvant gefitinib after complete resection also contained the T790M mutation.
      This mutation was not detected in untreated tumor samples. Moreover, no tumors
      with acquired resistance had KRAS mutations, which have been associated with
      primary resistance to these drugs. Biochemical analyses of transfected cells and
      growth inhibition studies with lung cancer cell lines demonstrate that the T790M
      mutation confers resistance to EGFR mutants usually sensitive to either gefitinib
      or erlotinib. Interestingly, a mutation analogous to T790M has been observed in
      other kinases with acquired resistance to another kinase inhibitor, imatinib
      (Gleevec). CONCLUSION: In patients with tumors bearing gefitinib- or erlotinib
      sensitive EGFR mutations, resistant subclones containing an additional EGFR
      mutation emerge in the presence of drug. This observation should help guide the
      search for more effective therapy against a specific subset of lung cancers.

PMID- 15737018
TI  - College of American Pathologists 2003 fresh frozen serum proficiency testing
      studies.

PMID- 15737021
TI  - Creatinine measurement: state of the art in accuracy and interlaboratory
      harmonization.
AB  - CONTEXT: The National Kidney Disease Education Program recommends calculating
      glomerular filtration rate from serum creatinine concentration. Accurate
      creatinine measurements are necessary for this calculation. OBJECTIVE: To
      evaluate the state of the art in measuring serum creatinine, as well as the
      ability of a proficiency testing program to measure bias for individual
      laboratories and method peer groups. DESIGN: A fresh-frozen, off-the-clot pooled
      serum specimen plus 4 conventional specimens were sent to participants in the
      College of American Pathologists Chemistry Survey for assay of creatinine.
      Creatinine concentrations were assigned by isotope dilution mass spectrometry
      reference measurement procedures. PARTICIPANTS: Clinical laboratories with an
      acceptable result for all 5 survey specimens (n = 5624). RESULTS: The fresh
      frozen serum (FFS) specimen had a creatinine concentration of 0.902 mg/dL (79.7
      micromol/L). Mean bias for 50 instrument-method peer groups varied from -0.06 to
      0.31 mg/dL (-5.3 to 27.4 micromol/L), with 30 (60%) of 50 peer groups having
      significant bias (P < .001). The bias variability was related to instrument
      manufacturer (P < or = .001) rather than method type (P = .02) with 24 (63%) of
      38 alkaline picric acid methods and with 6 (50%) of 12 enzymatic methods having
      significant biases. Two conventional specimens had creatinine concentrations of
      0.795 and 2.205 mg/dL (70.3 and 194.9 micromol/L) and had apparent survey biases
      significantly different (P < .001) from that of the FFS specimen for 34 (68%) and
      35 (70%) of 50 peer groups, respectively. CONCLUSIONS: Thirty of 50 peer groups
      had significant bias for creatinine. Bias was primarily associated with
      instrument manufacturer, not with type of method used. Proficiency testing using
      a commutable specimen measured participant bias versus a reference measurement
      procedure and provided trueness surveillance of instrument-method peer groups.

PMID- 15737020
TI  - Cell-by-cell dissection of gene expression and chromosomal interactions reveals
      consequences of nuclear reorganization.
AB  - The functional consequences of long-range nuclear reorganization were studied in
      a cell-by-cell analysis of gene expression and long-range chromosomal
      interactions in the Drosophila eye and eye imaginal disk. Position-effect
      variegation was used to stochastically perturb gene expression and probe nuclear
      reorganization. Variegating genes on rearrangements of Chromosomes X, 2, and 3
      were probed for long-range interactions with heterochromatin. Studies were
      conducted only in tissues known to express the variegating genes. Nuclear
      structure was revealed by fluorescence in situ hybridization with probes to the
      variegating gene and heterochromatin. Gene expression was determined alternately
      by immunofluorescence against specific proteins and by eye pigment
      autofluorescence. This allowed cell-by-cell comparisons of nuclear architecture
      between cells in which the variegating gene was either expressed or silenced.
      Very strong correlations between heterochromatic association and silencing were
      found. Expressing cells showed a broad distribution of distances between
      variegating genes and their own centromeric heterochromatin, while silenced cells
      showed a very tight distribution centered around very short distances, consistent
      with interaction between the silenced genes and heterochromatin. Spatial and
      temporal analysis of interactions with heterochromatin indicated that variegating
      genes primarily associate with heterochromatin in cells that have exited the cell
      cycle. Differentiation was not a requirement for association, and no differences
      in association were observed between cell types. Thus, long-range interactions
      between distal chromosome regions and their own heterochromatin have functional
      consequences for the organism.

PMID- 15737022
TI  - Comparison of pooled fresh frozen serum to proficiency testing material in
      College of American Pathologists surveys: cortisol and immunoglobulin E.
AB  - CONTEXT: The College of American Pathologists (CAP) provides proficiency testing
      (PT) surveys to laboratories around the world. OBJECTIVES: To compare diagnostic
      assay methods for serum/plasma cortisol and immunoglobulin (Ig) E in terms of
      their bias and precision, to determine how well CAP PT specimens simulate human
      serum, and to reassess proficiency test grading criteria in light of these
      findings. DESIGN: A participant-blinded, prospective trial. One vial of pooled
      fresh frozen serum (FFS) and 4 different admixtures of PT material (PTM) were
      sent to laboratories participating in PT surveys. PARTICIPANTS: Laboratories
      providing cortisol (>1000) or IgE (>230) results among the subscribers to the CAP
      surveys, Ligand (General) 2003, set K/KN-A and Chemistry 2003, set C-C. MAIN
      OUTCOME MEASURES: The main outcome measures were (1) bias among laboratories
      using the same method (peer groups), defined relative to the median of method
      means (MedMM); (2) imprecision as measured by the SD and coefficient of variation
      (CV) about each method mean; and (3) total error across laboratories for the FFS
      cortisol results, defined as |Bias Relative to Reference Method| + 2 SD. RESULTS:
      Cortisol method biases, relative to MedMM, ranged from -22% to 9% for the FFS
      challenge and from -24% to 36% for comparable PTM challenges. The method biases,
      relative to the reference method, ranged from -3% to 19% for the FFS challenge.
      The cortisol method CVs ranged from 4.2% to 13.6% for the FFS challenge and from
      4.7% to 12.7% for comparable PTM challenges. Total error across laboratories
      ranged from 1.4 to 6.9 microg/dL (39 to 190 nmol/L) for the FFS challenge.
      Immunoglobulin E method biases, relative to MedMM, ranged from -8% to 9% for the
      FFS challenge and from -7% to 5% for comparable PTM challenges. The IgE method
      CVs ranged from 3.6% to 6.7% for the FFS challenge and from 3.4% to 9.8% for
      comparable PTM challenges. CONCLUSIONS: The bias for cortisol results was less
      with FFS than with PTM, but imprecision was comparable. The FFS MedMM was 8.5%
      higher than the reference value. Fresh frozen serum and PTM bias and imprecision
      for IgE methods were each less than 10%. Because some of the methods demonstrated
      greater bias when analyzing PTM than FFS, peer group grading of both these
      analytes is appropriate.

PMID- 15737023
TI  - Analytic bias of thyroid function tests: analysis of a College of American
      Pathologists fresh frozen serum pool by 3900 clinical laboratories.
AB  - CONTEXT: In proficiency testing surveys, there are differences in the values
      reported by users of various analytic methods. Two contributors to this variation
      are calibrator bias and matrix effects of proficiency testing materials.
      OBJECTIVES: (1) To quantify the biases of the analytic methods used to measure
      thyroid-stimulating hormone, thyroxine, triiodothyronine, free thyroxine, and
      free triiodothyronine levels; (2) to determine if these biases are within
      allowable limits; and (3) to ascertain if proficiency testing materials correctly
      identify these biases. DESIGN: A fresh frozen serum specimen was mailed as part
      of the 2003 College of American Pathologists Ligand and Chemistry surveys. The
      means and SDs for each analytic method were determined for this sample as well as
      for a proficiency testing sample from both surveys. In the fresh frozen serum
      sample, target values for thyroxine and triiodothyronine were determined by
      isotope dilution/liquid chromatography/tandem mass spectrometry. All other target
      values in the study were the median of the means obtained for the various
      analytic methods. MAIN OUTCOME MEASURES: Calibration biases were calculated by
      comparing the mean of each analytic method with the appropriate target values.
      These biases were evaluated against limits based on intra- and interindividual
      biological variation. Matrix effects of proficiency testing materials were
      assessed by comparing the rank of highest to lowest analytic method means
      (Spearman rank test) for each analyte. PARTICIPANTS: Approximately 3900 clinical
      laboratories were enrolled in the College of American Pathologists Chemistry and
      Ligand surveys. RESULTS: The number of methods in the Ligand Survey that failed
      to meet the goals for bias was 7 of 17 for thyroid-stimulating hormone and 11 of
      13 for free thyroxine. The failure rates were 12 of 16 methods for thyroxine, 8
      of 11 for triiodothyronine, and 9 of 11 for free triiodothyronine. The means of
      the analytic method for the proficiency testing material correlated significantly
      (P < .05) only with the fresh frozen serum means for thyroxine and thyroid
      stimulating hormone in the Chemistry Survey and free triiodothyronine in the
      Ligand Survey. CONCLUSIONS: A majority of the methods used in thyroid function
      testing have biases that limit their clinical utility. Traditional proficiency
      testing materials do not adequately reflect these biases.

PMID- 15737024
TI  - Total long-term within-laboratory precision of cortisol, ferritin, thyroxine,
      free thyroxine, and thyroid-stimulating hormone assays based on a College of
      American Pathologists fresh frozen serum study: do available methods meet medical
      needs for precision?
AB  - CONTEXT: It is important that the total long-term precision of laboratory methods
      meet the medical needs of the patients being served. OBJECTIVES: To determine the
      long-term within- and between-laboratory variation of cortisol, ferritin,
      thyroxine, free thyroxine, and thyroid-stimulating hormone measurements using
      commonly available methods and to determine if these variations are within
      accepted medical needs. DESIGN: Two vials of pooled frozen serum were mailed 6
      months apart to laboratories participating in 2 separate College of American
      Pathologists surveys. The data from those laboratories that analyzed an analyte
      in both surveys were used to determine for each method the total variance and the
      within- and between-laboratory components. SETTING: The study included the A
      mailing of the 2003 College of American Pathologists Ligand Survey and the C
      mailing of the Chemistry Survey. MAIN OUTCOME MEASURES: For each analyte, total
      variance was partitioned into within- and between-laboratory components for each
      analytic method. The within-laboratory variations were then compared with
      imprecision criteria based on biological variation. PARTICIPANTS: The
      laboratories that reported results on the same analyte using the same method in
      both surveys. RESULTS: For each analyte, the median of the long-term within
      laboratory variances of each peer group was 78% to 95% of its total-survey
      variance, and the median long-term within-laboratory coefficients of variation
      varied from 5.1% to 7.6%. The number of methods that met within-laboratory
      imprecision goals based on biological criteria were 5 of 5 for cortisol; 5 of 7
      for ferritin; 0 of 7 for thyroxine and free thyroxine; and 8 of 8 for thyroid
      stimulating hormone. CONCLUSIONS: For all analytes tested, the total within
      laboratory component of variance was the major source of variability in this
      study. In addition, there are several methods, especially for thyroxine and free
      thyroxine, that may not meet analytic goals in terms of their imprecision.

PMID- 15737025
TI  - Comparison of fresh frozen serum to traditional proficiency testing material in a
      College of American Pathologists survey for ferritin, folate, and vitamin B12.
AB  - CONTEXT: Comparison of different analytical methods in proficiency surveys may be
      affected by the artificial nature of the survey material. OBJECTIVE: To compare
      intermethod differences in proficiency survey results between 2 types of survey
      material, conventional proficiency testing material (PTM) and fresh frozen human
      serum (FFS), for 3 markers of anemia: ferritin, folate, and vitamin B12. DESIGN:
      Data were gathered from a 2003 survey event in the College of American
      Pathologists Ligand ("K") Series, in which the specimens to be tested by each
      participating laboratory included 1 vial of FFS and 2 vials of PTM with different
      analyte concentrations. The more than 1600 laboratories subscribing to the survey
      were not advised as to the nature of the specimens. MAIN OUTCOME MEASURES: The
      bias of each method relative to the median of method means for each analyte and
      each type of survey material, and the interlaboratory coefficient of variation
      for each method. RESULTS: For each of the 3 analytes, moderate to large method
      biases were observed. For ferritin, method biases correlated strongly between
      comparable PTM and FFS specimens (Spearman r = 0.863, P < .001), whereas
      virtually no correlation was found for folate (r = -0.224, P = .48), and a
      marginally significant correlation existed for B12 (r = 0.55, P = .049).
      CONCLUSIONS: With ferritin, proficiency survey performance of PTM is similar to
      that of FFS, implying that method biases relate mainly to calibration. With
      folate and to a lesser extent with B12, PTM and FFS exhibit different method
      biases, implying that the biases reflect analyte heterogeneity and/or matrix
      effects.

PMID- 15737026
TI  - A comparison of human chorionic gonadotropin- related components in fresh frozen
      serum with the proficiency testing material used by the College of American
      Pathologists.
AB  - CONTEXT: As part of a College of American Pathologists (CAP) proficiency testing
      survey, a comparison is made between human chorionic gonadotropin (hCG) results
      from an actual patient pool and a similarly targeted artificial sample. The goal
      is to gain insight into the possible source(s) of bias attributable to the
      proficiency testing material (PTM) with a view toward creating more appropriate
      survey materials. OBJECTIVE: To compare hCG and related variants in a pool of
      fresh frozen sera (FFS) with that found in PTM. DESIGN: The 2003 CAP K/KN-A
      Survey included a FFS specimen along with admixtures of PTM. The FFS (K-02) and 1
      PTM admixture (K-01) had similar mean hCG values. Five hCG-related analytes were
      measured on these 2 samples by a reference laboratory. PARTICIPANTS:
      Approximately 1800 clinical laboratories and diagnostic test kit manufacturers
      participated in the K/ KN-A Survey. MAIN OUTCOME MEASURES: Method imprecision
      (coefficient of variation) and method bias (relative difference between peer
      group mean and all-method median) were computed for the 2 samples. Differences
      were evaluated with respect to hCG-related analytes levels. RESULTS: All-method
      hCG results were 12.9 mIU/mL (12.9 IU/L) for the PTM material and 21.6 mIU/mL
      (21.6 IU/L) for the FFS material. Method biases for 14 manufacturers were greater
      for PTM than for FFS (-40% to +35% and -16% to +23%). Twelve of 14 methods had
      higher coefficients of variation on PTM. Total hCG and free beta hCG measurements
      by the reference laboratory were 14.1 mIU/ mL (14.1 IU/L) for the PTM material
      and 18.5 mIU/mL (18.5 U/L) for the FFS material (FFS), and 2.4 (PTM) and 0.7
      (FFS) mIU/mL (2.4 and 0.7 IU/L), respectively. On a molar basis, free beta
      represented 17% and 4% of the total hCG, respectively. Levels of
      hyperglycosylated hCG, nicked hCG, and beta core fragment were not measurable in
      either sample. CONCLUSIONS: It is unlikely that the hCG added to the PTM is the
      source of the increased bias and variability. The main difference is a 3-fold
      increase in free beta found in the PTM, but methods previously found to strongly
      react with free beta were not systematically elevated. The biases between
      manufacturers found for the FFS specimen are likely attributable to calibration
      differences.

PMID- 15737027
TI  - Comparison of fresh frozen serum to proficiency testing material in College of
      American Pathologists surveys: alpha-fetoprotein, carcinoembryonic antigen, human
      chorionic gonadotropin, and prostate-specific antigen.
AB  - CONTEXT: Most proficiency testing materials (PTM) contain an artificial matrix
      that may cause immunoassays to perform differently with this material than with
      clinical samples. We hypothesized that matrix effects would be reduced by using
      fresh frozen serum (FFS). OBJECTIVE: To compare the performance of an FFS pool to
      standard PTM for measurement of alpha-fetoprotein, carcinoembryonic antigen,
      human chorionic gonadotropin (hCG), and prostate-specific antigen (PSA). DESIGN:
      One FFS specimen and 4 different admixtures of PTM were distributed in the 2003
      College of American Pathologists K/KN-A (for alpha-fetoprotein, carcinoembryonic
      antigen, hCG, and total and free PSA) and C-C (hCG only) Surveys. PARTICIPANTS:
      The number of laboratories that participated in the surveys varied from a low of
      288 (free PSA, K/KN-A Survey) to a high of 2659 (hCG, C-C Survey). MAIN OUTCOME
      MEASURES: Method imprecision and method bias were compared between the FFS
      specimen and the standard PTM specimen with the closest value. Method imprecision
      was determined by calculating the coefficients of variation for each method and
      for all methods combined. Bias was defined as the proportional difference between
      peer-group mean and the median of all method means. RESULTS: The FFS specimen
      gave significantly higher imprecision than PTM for the analytes alpha
      fetoprotein, carcinoembryonic antigen, total PSA, and free PSA. For hCG, no
      substantial imprecision differences were observed in both surveys. Bias was
      significantly greater for the alpha-fetoprotein, carcinoembryonic antigen, and
      total PSA assays and significantly lower for the hCG and free PSA assays when
      comparing the FFS with the PTM. CONCLUSIONS: Fresh frozen serum did not provide
      consistently lower imprecision or bias than standard PTM in a survey of commonly
      ordered tumor markers.

PMID- 15737028
TI  - Utility of immunohistochemistry in distinguishing primary adenocarcinomas from
      metastatic breast carcinomas in the gastrointestinal tract.
AB  - CONTEXT: Breast carcinoma often metastasizes to the gastrointestinal tract,
      especially the stomach, where it is frequently difficult to distinguish from a
      primary gastric carcinoma. OBJECTIVE: To evaluate the utility of
      immunohistochemical stains in differentiating primary gastric carcinomas from
      metastatic breast carcinomas. DESIGN: Mucosal biopsy specimens from 47
      adenocarcinomas involving the gastrointestinal tract (28 primary gastric
      carcinomas and 19 metastatic breast carcinomas) and 16 control cases of primary
      breast carcinomas without metastasis were immunohistochemically stained for
      estrogen receptor protein (ER), progesterone receptor protein (PR), gross cystic
      disease fluid protein (GCDFP), human epidermal growth factor receptor 2 protein,
      cytokeratin (CK) 5/6, CK/7, CK/20, a panel of mucin glycoprotein antigens (MUC2,
      MUC3, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox
      transcription factor CDX2 and compared between primary and metastatic
      adenocarcinomas. RESULTS: Highly significant proportions of metastatic breast
      carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%)
      compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6,
      14%) (P < .001, P = .002, P < .001, and P = .004, respectively). Of these
      immunostains, ER, PR, and GCDFP were 100% specific. Primary breast tumors and
      their metastases showed a similar phenotypic profile. In contrast, primary
      gastric carcinomas showed significantly higher proportions of cases that stained
      with CK20 (50%), MUC2 (54%), MUC5AC (71%), MUC6 (39%), DAS-1 (43%), and CDX2
      (67%) compared with metastatic breast carcinomas (CK20, 0%; MUC2, 24%; MUC5AC,
      6%; MUC6, 0%; DAS-1, 0%; and CDX2, 0%) (P = .001, P = .01, P < .001, P = .02, P =
      .009, and P < .001, respectively). No significant differences were observed with
      regard to any of the other immunostains (human epidermal growth factor receptor 2
      protein, CK7, and MUC3) between the patient groups. CONCLUSIONS: Estrogen
      receptor protein, PR, GCDFP, CK5/6, CK20, MUC5AC, MUC6, DAS-1, and CDX2 are
      helpful in distinguishing primary gastric carcinomas from metastatic breast
      carcinomas. Of these, ER, PR, and GCDFP are highly specific for metastatic breast
      carcinomas, whereas CK20, DAS-1, MUC2, MUC5AC, MUC6, and CDX2 are highly specific
      for primary gastric carcinomas.

PMID- 15737029
TI  - Dendriform pulmonary ossification, a form of diffuse pulmonary ossification:
      report of a 26-year autopsy experience.
AB  - CONTEXT: Dendriform pulmonary ossification (DPO) is an uncommon form of diffuse
      pulmonary ossification that typically affects the pulmonary interstitium in a
      setting of interstitial fibrosis. OBJECTIVE: To determine the incidence and
      characteristics of DPO and correlate the clinical, radiographic, and pathologic
      features in order to better understand its pathogenesis and behavior and
      facilitate proper therapy. DESIGN: Adult autopsies performed at a tertiary care
      center from 1978 to 2004 were reviewed to identify cases of DPO. Clinical,
      radiographic, and pathologic findings, including ultrastructural studies in
      select cases, were analyzed and correlated. RESULTS: Eight cases of DPO were
      identified from 1393 adult autopsies. None of the cases was diagnosed antemortem.
      The prevalence of DPO was 0.5%, and the incidence was 0.28 cases per year. Most
      patients had a history of chronic lung disease, and all were 65 years of age or
      older. CONCLUSIONS: Dendriform pulmonary ossification is an uncommon and unusual
      entity seen incidentally at autopsy and associated with chronic lung disease. It
      is well demonstrated in postmortem examination, confirmed by microscopy and
      ultrastructural study, but rarely diagnosed and virtually never considered
      clinically. Clinical diagnoses include bronchiectasis and interstitial
      pneumonitis based on radiographic evidence. With its associated
      radiographic/pathologic findings, DPO should be considered in the differential
      diagnosis of chronic lung disease.

PMID- 15737030
TI  - Perineural and vascular invasion in oral cavity squamous carcinoma: increased
      incidence on re-review of slides and by using immunohistochemical enhancement.
AB  - CONTEXT: Perineural invasion and vascular invasion may be adverse prognostic
      factors in patients with oral cavity squamous cell carcinoma. However, the
      incidence of perineural and vascular invasion varies in the literature, and the
      use of immunohistochemistry to enhance their detection has not been evaluated in
      oral cavity squamous cell carcinomas. OBJECTIVE: To determine if the previously
      assessed incidence of perineural and vascular invasion in cases of oral cavity
      squamous cell carcinoma would be increased by re-review of the original routinely
      hematoxylin-eosin-stained sections as well as review of slides stained
      immunohistochemically with S100 and CD31 to enhance visualization of nerves and
      vessels. DESIGN: Forty cases of oral cavity squamous cell carcinoma in which the
      status of perineural and vascular invasion had been part of the original
      pathology report were reviewed. All original routinely stained slides were
      reviewed as well as S100- and CD31-stained sections of each case's tissue blocks
      that contained tumor. RESULTS: Perineural invasion was identified in 30% (12/ 40)
      of tumors in the original reports, 62% (25/40) of the authors' re-review of the
      same slides, and 82% (33/40) when cases were stained with S100. Vascular invasion
      was identified in 30% (12/40) of tumors in the original reports, 35% (14/40) of
      the authors' re-review of the same slides, and 42% (17/40) when cases were
      stained with CD31. False-positive and false-negative results were common in the
      original reports. The number of foci of both types of invasion was related to its
      discovery in the original reports. Vascular invasion, but not perineural
      invasion, was significantly associated with death at 5-year follow-up.
      CONCLUSIONS: Although careful re-review of routinely stained slides will detect a
      significant number of cases of perineural and vascular invasion,
      immunohistochemical enhancement further improves the accuracy of the
      determination.

PMID- 15737032
TI  - Pulmonary complications after bone marrow transplantation: an autopsy study from
      a large transplantation center.
AB  - CONTEXT: Bone marrow transplantation (BMT) is used to treat various malignant and
      nonmalignant disorders. Pulmonary complications are some of the most common
      causes of mortality in BMT recipients. Poor general health and bleeding tendency
      frequently preclude the use of definitive diagnostic tests, such as open lung
      biopsy, in these patients. OBJECTIVE: To identify pulmonary complications after
      BMT and their role as the cause of death (COD). DESIGN: The autopsy and
      bronchoalveolar lavage (BAL) slides and microbiology studies of BMT recipients
      from a 7-year period were reviewed. RESULTS: Pulmonary complications were
      identified in 40 (80%) of the 50 cases. The most common complications were
      diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH). Pulmonary
      complications were the sole or 1 of multiple CODs in 37 cases (74%). All
      complications were more common in allogeneic BMT recipients. In 19 (51%) of the
      37 cases in which pulmonary complications contributed to the death, cultures were
      negative. Both DAD and DAH, complications commonly reported in the early post-BMT
      period, were seen more than 100 days after BMT in 33% and 12% of cases,
      respectively. Five (83%) of 6 cases of invasive pulmonary aspergillosis diagnosed
      at autopsy were negative for fungi ante mortem (by BAL and cultures).
      CONCLUSIONS: Pulmonary complications are a significant COD in BMT recipients,
      many of which, especially the fungal infections, are difficult to diagnose ante
      mortem. The etiology of DAD and DAH is likely to be multifactorial, and these
      complications are not limited to the early posttransplantation period. Autopsy
      examination is important in determining the COD in BMT recipients.

PMID- 15737031
TI  - Giant cell tumors: inquiry into immunohistochemical expression of CD117 (c-Kit),
      microphthalmia transcription factor, tartrate-resistant acid phosphatase, and HAM
      56.
AB  - CONTEXT: Osteoclast-like giant cells (GCs) in giant cell tumors (GCTs) are
      thought to derive from a monocyte-macrophage lineage. Microphthalmia
      transcription factor (MITF) is necessary for osteoclast gene expression and
      tartrate-resistant acid phosphatase (TRAP) activation; c-Kit plays a role in
      regulation of MITF. OBJECTIVE: To gain insight into the differentiation of GCTs
      of bone (GCTBs) and GCTs tendon sheath (GCTTSs) by investigating
      immunohistochemical staining for c-Kit, MITF, TRAP, and HAM-56 in the GCs and
      stroma. DESIGN: Immunoreactivity for CD117 (c-Kit), MITF, TRAP, and HAM-56 was
      studied in 35 GCTBs, 15 GCTTSs, and 5 foreign-body GC controls. RESULTS: Across
      tumors, MITF and TRAP but not c-Kit were generally expressed in GCs; TRAP was
      variably expressed in stromal cells. The MITF was expressed more consistently in
      stromal cells of GCTTSs than GCTBs (P < .001). The GCTBs showed more intense MITF
      stromal (P < .001) and TRAP GC staining (P = .04) than GCTTSs. HAM-56 staining by
      stromal cells was associated with MITF stromal staining (r2 = 0.6, P < .001).
      CONCLUSIONS: Results suggest that MITF and TRAP are expressed during osteoclast
      differentiation and that a proportion of mononuclear cells in GCTs express the
      macrophage marker HAM-56. Both GCTBs and GCTTSs show similar patterns of
      immunohistochemical expression.

PMID- 15737033
TI  - Usefulness of cutaneous T-cell clonality analysis for the diagnosis of cutaneous
      T-cell lymphoma in patients with erythroderma.
AB  - CONTEXT: Demonstration of a dominant T-cell clone in skin biopsy specimens by a
      molecular assay constitutes an additional diagnostic criterion to differentiate
      cutaneous T-cell lymphomas (CTCLs) from inflammatory dermatoses. OBJECTIVE: To
      determine which patients, depending on their clinical presentations, could most
      benefit from a cutaneous T-cell clonality analysis in addition to histopathologic
      analysis for the diagnosis of CTCL. DESIGN: Comparison of sensitivity and
      specificity of histopathologic analysis and a combination of this method and the
      detection of a T-cell receptor gamma chain gene rearrangement by polymerase chain
      reaction denaturing gradient gel electrophoresis performed on skin biopsy
      specimens obtained at initial presentation. PATIENTS: One hundred forty
      consecutive patients were classified into 4 groups, depending on their clinical
      presentation: (1) eczematous patches suggestive of early-stage mycosis fungoides
      (MF) (IA and IB of the TNM classification) (n = 42); (2) plaques, nodules, or
      tumors that arise on or are associated with plaques suggestive of late-stage MF
      (IIB and III of the TNM classification) (n = 16); (3) erythroderma (n = 50); and
      (4) nodules or tumors that arise in normal skin, suggestive of non-MF CTCL (n =
      32). RESULTS: When compared with histopathologic examination, the addition of
      clonality analysis increased the sensitivity of CTCL diagnosis in all groups of
      patients except those with cutaneous lesions suggestive of late-stage MF, because
      the diagnosis was made based on histopathologic analysis alone in 100% of these
      cases. The main increase in sensitivity of CTCL diagnosis was observed in
      patients with erythroderma: 62% with histopathologic analysis alone to 87% with
      the combination of both methods (P = .04). Diagnostic specificity of molecular
      assays decreased from 100% to 76% (P = .01) in patients with patch lesions and
      from 100% to 70% (P = .04) in patients with nodules that occurred in normal skin
      due to the detection of a T-cell clone in 6 patients with follicular mucinosis
      without a histologic pattern of MF and in 5 of 20 cases of T-cell pseudolymphoma
      (25%), respectively. In contrast, a T-cell clone was not detected in the 34
      patients with erythroderma of inflammatory origin. CONCLUSION: Polymerase chain
      reaction analysis of cutaneous T-cell clonality could be useful for the diagnosis
      of CTCL in patients who present with erythroderma.

PMID- 15737034
TI  - Epstein-Barr virus in breast carcinoma in Argentina.
AB  - CONTEXT: Because the etiology and progression of breast carcinoma remain unclear,
      novel mechanisms of disease pathogenesis need to be considered. Recent interest
      has focused on Epstein-Barr virus (EBV), an oncogenic ubiquitous herpesvirus.
      Investigations of this association could not only broaden understanding of breast
      cancer etiology but also have implications regarding early detection, treatment,
      and prevention. OBJECTIVE: To assess EBV presence in breast carcinoma in an
      Argentine series. DESIGN: Breast biopsy specimens of 69 women with breast
      carcinoma and fresh tumor tissue of 39 of these women were collected. As
      controls, 17 biopsy specimens of fibroadenomas, 9 of benign epithelial
      proliferation, 4 of atypical ductal hyperplasia, and 10 of usual ductal
      hyperplasia and 8 normal breast tissues from women were studied. The EBV-infected
      cells were identified by means of immunohistochemical analysis, using a
      monoclonal antibody against Epstein-Barr virus-encoded nuclear antigen 1 (EBNA
      1). Polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers
      that cover the EBV encoded RNA (EBER) and BamHIW regions. RESULTS: Nuclear
      expression of EBNA-1 was observed in tumor epithelial cells in 24 (35%) of the 69
      cases. We confirmed both positive and negative immunohistochemical results by PCR
      in those cases where good quality DNA was also available, detecting amplification
      fragments of 108 base pairs (bp) from the EBER region and 122 bp from the BamHIW
      region. Neither immunohistochemical analysis nor PCR detected any positive EBV
      results in the control samples. CONCLUSIONS: Our results demonstrate the presence
      and expression of EBV restricted to epithelial tumor cells in a subset of breast
      carcinomas studied. However, no significant association was observed between EBV
      expression and worse clinical and pathologic patient characteristics.

PMID- 15737035
TI  - The openings of uteroplacental vessels with villous infiltration at different
      gestational ages.
AB  - CONTEXT: The number of uteroplacental vessels flowing into the intervillous space
      in mature placentas has been reported in some studies to increase and in others
      to decrease. Both villous infiltration and proliferation in the vessels have been
      neglected in histologic examinations and need to be studied. OBJECTIVE: To
      clarify these conflicting findings regarding villous infiltration and
      proliferation in the uteroplacental vessels. DESIGN: A retrospective study was
      done using placental sections of different gestational ages. The openings of the
      vessels in each section were counted, noting if they were with or without villous
      infiltration. The frequency of openings per section was calculated, and the
      findings were grouped by gestational age. RESULTS: The frequency of total
      openings was significantly lower in the 41 to 37 weeks group (1.2) than in the 36
      to 30 weeks group (2.0), the 29 to 20 weeks group (2.2), and the 19 to 13 weeks
      group (2.4) (P < .001). The frequency of openings with villous infiltration
      decreased similarly in mature placentas. Chorionic villi infiltrated the openings
      and proliferated in uteroplacental vessels. Differentiation between arteries and
      veins was difficult in the basal plate, because all vessels had veinlike
      structures. CONCLUSIONS: This decreasing frequency of openings in mature
      placentas suggests that the amount of intervillous blood flow is limited in full
      term and postterm pregnancy. Villous infiltration into the vessels is considered
      a normal finding with gestation and can provide trophoblast for uteroplacental
      arteries. The relationship between placental development and villous
      proliferation in the vessels is presented.

PMID- 15737036
TI  - Putative precursors of gallbladder dysplasia: a review of 400 routinely resected
      specimens.
AB  - CONTEXT: Dysplasia is thought to be a precursor of invasive gallbladder
      carcinoma, but it is unsettled whether dysplasia arises from other precursor
      lesions. OBJECTIVE: To ascertain the presence and nature of precursors of
      dysplasia in the gallbladder. DESIGN: Four hundred consecutive cholecystectomy
      specimens were processed and stained routinely for diagnosis. We retrospectively
      reviewed these cases to look for the presence of epithelial changes, including
      antral-type metaplasia, intestinal metaplasia, and dysplasia. RESULTS: Antral
      type metaplasia, intestinal metaplasia, and dysplasia were found in 238 (59.5%),
      39 (9.8%), and 20 (5.0%) cases, respectively. The mean patient age was 47.7 years
      (range, 15-93 years). The mean ages for patients with antral-type metaplasia,
      intestinal metaplasia, and dysplasia were 49.4, 50.9, and 52.6 years,
      respectively. Statistically significant associations were found between antral
      type metaplasia and intestinal metaplasia (P = .007, chi2 test) and between
      intestinal metaplasia and dysplasia (P < .001, chi2 test). CONCLUSION: These
      associations, along with the age gradient from antral-type metaplasia to
      dysplasia, suggest a progression from antral-type metaplasia to dysplasia via
      intestinal metaplasia.

PMID- 15737037
TI  - Recurrence of nodal diffuse large B-cell lymphoma as intravascular large B-cell
      lymphoma: is an intravascular component at initial diagnosis predictive?
AB  - We report a case of a 59-year-old man who first presented with a nodal diffuse
      large B-cell lymphoma that later relapsed as an intravascular large B-cell
      lymphoma. In the initial biopsy specimen, a few intranodal small vessels that
      contained large lymphoma cells were noted. After 8 months of multiagent
      chemotherapy, clinical remission was attained. Two years after the initial
      diagnosis of nodal diffuse large B-cell lymphoma, the patient presented with a
      rapid onset of multiorgan failure, which at autopsy was shown to be due to
      intravascular large B-cell lymphoma. Molecular genetic studies showed that these
      2 lymphomas had immunoglobulin heavy-chain gene rearrangements that were of
      identical size, suggesting that they were derived from the same clone. To our
      knowledge, this is the first report of a nodal large B-cell lymphoma that
      relapsed as an intravascular large B-cell lymphoma. Although this report is of
      only a single case, the presence of a relatively inconspicuous intravascular
      component in an otherwise typical nodal large B-cell lymphoma may be predictive
      and could affect clinical decisions regarding diagnosis, monitoring, and
      prognosis of such lymphomas.

PMID- 15737038
TI  - Hairy cell leukemia variant with features of intrasinusoidal bone marrow
      involvement.
AB  - Hairy cell leukemia variant (HCL-V) is a rare lymphoproliferative disorder. We
      report a case of HCL-V with an intrasinusoidal pattern of bone marrow involvement
      without interstitial or diffuse infiltration that is typical of HCL and its
      variant. The peripheral blood and bone marrow aspirates demonstrated abnormal
      lymphoid cells with cytoplasmic projections that were weakly positive for
      tartrate-resistant acid phosphatase cytochemical staining. Immunostaining of the
      bone marrow biopsy specimen showed that these cells were strongly positive for
      CD20, located within bone marrow sinusoids, and weakly positive for DBA44. By
      flow cytometry, these cells were positive for CD19, CD20, CD11c, and CD103,
      exhibited lambda light chain restriction, and were negative for CD25. The patient
      was initially diagnosed as having splenic lymphoma with villous lymphocytes
      (SLVL) or splenic marginal zone lymphoma (SMZL) (World Health Organization
      designation) and treated with fludarabine followed by splenectomy with
      simultaneous liver biopsy. The pathologic analysis of the spleen revealed
      infiltration of red pulp by the critical cells without white pulp involvement,
      which is characteristic of HCL and HCL-V but not of SLVL (SMZL). This case
      illustrates an atypical marrow presentation of HCL-V and emphasizes the need to
      correlate all clinical and pathologic data, including tissue biopsy, in reaching
      a diagnosis.

PMID- 15737039
TI  - Intratesticular mucinous cystadenoma: immunohistochemical comparison with ovarian
      and colonic tissue.
AB  - We report a case of a primary intratesticular mucinous cystadenoma in an
      asymptomatic 39-year-old man. The mass was found incidentally during a
      consultation for infertility. Pathologic examination of the orchiectomy specimen
      revealed a unilocular cyst lined with bland mucinous epithelium and mucinous
      extravasation, consistent with a diagnosis of mucinous cystadenoma. Foci of bone
      were also found in association with extensive chronic inflammation.
      Immunohistochemical stains performed showed immunoreactivity for cytokeratin 7,
      and nonreactivity for cytokeratin 20, CA125, chromogranin, and synaptophysin. The
      immunohistochemical staining patterns of the present case are compared with those
      of known mucinous cystadenomas of the ovary and nonneoplastic colonic mucosa. The
      histogenesis of this entity is discussed in light of the literature and the
      immunohistochemical findings in this rare case.

PMID- 15737040
TI  - Malignant deciduoid mesothelioma: a diagnostic challenge.
AB  - Malignant deciduoid mesothelioma, a rare phenotype of epithelioid mesothelioma,
      arises more commonly from the peritoneum of young women, but it is also reported
      in the pleura of elderly people. We report a case of malignant deciduoid
      mesothelioma that occurred in a 41-year-old woman after cesarean section and was
      initially misdiagnosed as pseudotumoral deciduosis. Microscopically, the tumor
      was entirely composed of deciduoid areas, and only scattered tumor cells were
      positive for calretinin and keratin 5/6. The patient died 14 months after the
      first operation. This observation confirms the poor prognosis of this entity and
      the importance of the differential diagnosis of pseudotumoral deciduosis.

PMID- 15737042
TI  - Detection of t(14;18)(q32;q21) in B-cell chronic lymphocytic leukemia.
AB  - Cytomorphologic testing and multiparameter flow cytometry are the mainstays in
      diagnosing B-cell chronic lymphocytic leukemia, whereas fluorescence in situ
      hybridization that targets the translocation t(14;18)(q32;q21) often is used to
      identify follicular lymphoma. Therapy is highly diverse between both diseases. We
      describe a case with cytomorphologically and immunologically proven B-cell
      chronic lymphocytic leukemia in which t(14;18)(q32;q21) was found.

PMID- 15737041
TI  - Collision tumor of the stomach: a rare case of an adenocarcinoma and carcinoid
      tumor.
AB  - We report a rare case of gastric collision tumor composed of moderately
      differentiated tubular adenocarcinoma and carcinoid in an 84-year-old woman. On
      endoscopic examination, an invasive tumor was noted at the cardia of the stomach,
      and a pathologic examination of the biopsy specimen revealed adenocarcinoma.
      After total gastrectomy, a thorough histopathologic examination of the resected
      tumor revealed the concurrent presence of moderately differentiated
      adenocarcinoma and a typical carcinoid tumor, which had a colliding pattern of
      tissue proliferation. There was no intermixing or transition area between the 2
      components. The final pathologic diagnosis was collision tumor of the
      adenocarcinoma and carcinoid tumor. The presence of either tumor individually
      would not be especially noteworthy, but this collision-type tumor of both
      histopathologic types in the stomach is, to our knowledge, only the sixth such
      case in the literature.

PMID- 15737043
TI  - Pathologic quiz case: a 44-year-old woman with a tubulovillous adenoma of the
      colon and liver and bone lesions. Small cell (neuroendocrine) carcinoma of the
      colon with metastasis and an associated, overlying villous adenoma.

PMID- 15737044
TI  - Pathologic quiz case: an unusual cause of acromegaly. Intrasellar gangliocytoma.

PMID- 15737045
TI  - Pathologic quiz case: a 39-year-old woman with nausea, vomiting, diarrhea, and
      weight loss. Menetrier disease.

PMID- 15737046
TI  - Pathologic quiz case: multiple splenic nodules. Splenic sarcoid.

PMID- 15737047
TI  - Malignant phyllodes tumor with liposarcomatous differentiation.

PMID- 15737048
TI  - Chronic myelogenous leukemia in sickle cell anemia.

PMID- 15737049
TI  - Acute monocytic leukemia with cutaneous manifestation.

PMID- 15737050
TI  - Rhabdoid tumor of the thyroid gland: a variant of anaplastic carcinoma.
AB  - Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by
      significant metastatic potential. All of the 6 cases reported in the recent
      literature had poor outcomes. We report an additional case involving, to our
      knowledge, the oldest patient reported so far. A 67-year-old woman had a nodular
      goiter for all of her adult life and presented with a rapidly growing mass in the
      right lobe. Histologic examination showed a highly cellular neoplasm with a solid
      infiltrative growth pattern. Extracapsular invasion was evident. Rhabdoid cells
      were large, with abundant cytoplasm, eosinophilic inclusions, and eccentric
      nuclei containing distinct nucleoli. Immunohistochemistry identified vimentin,
      sarcomeric actin, myoglobin, and cytokeratin expression in the tumor cells; they
      were negative for desmin, thyroglobulin, and calcitonin. Scattered follicles with
      nuclear features of papillary thyroid carcinoma were detected; these cells were
      immunoreactive for thyroglobulin and TTF-1. Reverse transcriptase polymerase
      chain reaction using specific primers for RET/PTC1 and RET/PTC3 fusion genes
      identified a RET/PTC3 gene rearrangement in the rhabdoid tumor. Despite
      radiotherapy, the neoplasm rapidly progressed, with massive local and mediastinal
      metastasis leading to death 5 months after presentation. The hypothesis that
      rhabdoid tumor is a variant of anaplastic thyroid carcinoma is supported by the
      identification of a RET/PTC gene rearrangement, a feature of carcinomas of
      follicular cell derivation.

PMID- 15737051
TI  - Nodular mucinosis of the breast: a case report with pathologic, ultrasonographic,
      and clinical findings and review of the literature.
AB  - Nodular mucinosis is an extremely rare breast lesion. This benign mass usually
      presents clinically as a poorly circumscribed, subareolar, myxoid mass in young
      female patients. We report a case of this rare breast lesion and discuss its
      clinical, radiologic, and histopathologic features. A 21-year-old white woman
      presented with a mass in the left breast of 6 months' duration. She had never
      been pregnant or had any history of breast feeding, surgery, trauma, or use of
      exogenous hormones or a family history of breast cancer. Clinical breast
      examination demonstrated a 1 cm "rubbery" mass directly under and continuous with
      the left nipple. The skin that covered the mass had an edematous and irregular
      appearance without erythema or drainage from the nipple. Ultrasonography
      demonstrated a 1-cm, nonintraductal, circumscribed, homogeneous, isoechoic mass
      that was continuous or part of the base of the left nipple. The mass was smooth,
      with a thin echogenic rim. Doppler flow showed some vascularity. These findings
      suggested a benign breast lesion, including a fibroadenoma or nipple adenoma.
      Despite reassurance, the patient desired excision of the lesion. Gross
      examination revealed a nodular, rubbery-firm, ovoid, pink, polypoid mass that
      measured 1.5 x 0.9 x 0.8 cm. Microscopic examination showed a well-circumscribed
      tumor with a nodular appearance, which consisted of an accumulation of pink
      myxoid tissue and contained spindle cells with bland-appearing nuclei, no
      mitosis, and mild cellularity. The pink myxoid tissue was stained with Hale
      colloidal iron and Alcian blue. The Alcian blue stain was removed by pretreatment
      with hyaluronidase. The spindle cells stained with vimentin and smooth muscle
      actin; however, they did not express smooth muscle myosin or cytokeratin. This
      report presents and discusses the pathologic, ultrasonographic, and clinical
      findings of this rare entity.

PMID- 15737052
TI  - Intraductal papillary mucinous adenoma that arises from pancreatic heterotopia
      within a meckel diverticulum.
AB  - Neoplasia is an unusual complication of Meckel diverticulum. Most tumors of
      Meckel diverticulum are neuroendocrine or mesenchymal in origin. Adenocarcinomas
      represent a minority of the tumors that arise in Meckel diverticulum and are
      generally thought to develop from either endogenous small intestinal epithelium
      or heterotopic gastric epithelium. Despite the presence of ectopic pancreas in a
      small fraction of Meckel diverticula, convincing evidence of tumors that arise
      from heterotopic pancreatic exocrine tissue has not been described in this
      setting. Intraductal papillary mucinous neoplasms are relatively uncommon tumors
      of pancreatic ductal epithelial cells that line the main pancreatic duct or its
      major side branches. We present an unusual case of an intraductal papillary
      mucinous neoplasm that arose in a heterotopic pancreas within a Meckel
      diverticulum.

PMID- 15737053
TI  - Pathologic quiz case: a 39-year-old man with severe lower back pain. Plasma cell
      leukemia.

PMID- 15737054
TI  - Pathologic quiz case: sphenoid sinus mass in a 12-year-old girl. Infrasellar
      adamantinomatous craniopharyngioma.

PMID- 15737055
TI  - Pathologic quiz case: a large, ill-defined cystic breast mass. Invasive cystic
      hypersecretory duct carcinoma.

PMID- 15737057
TI  - Pathologic quiz case: a 55-year-old man with chronic maxillary sinusitis.
      Synchronous occurrence of Aspergillosis and myospherulosis.

PMID- 15737056
TI  - Pathologic quiz case: a 44-year-old man with acute renal failure. Toxic acute
      tubular necrosis secondary to ingestion of ethylene glycol.

PMID- 15737058
TI  - Verucciform xanthoma of the penis not associated with human papillomavirus
      infection.
AB  - Verruciform xanthoma (VX) is a rare lesion with a predilection for oral mucosa.
      Only 16 cases of VX of the penis have been reported. Histologically, VX lesions
      in different locations are identical; however, the etiology is controversial.
      Previous studies have reported the presence of human papillomavirus (HPV) in VX
      of the skin. The purpose of this study was to determine whether HPV is a
      causative agent in this rare case of VX of the penis. Microscopically, the lesion
      demonstrated prominent verrucoid squamous hyperplasia with hyperkeratosis,
      parakeratosis, and acanthosis. Histiocytes, a hallmark of VX, were identified in
      the elongated dermal papillae. Nested polymerase chain reaction was performed on
      the DNA with the commonly used primer sets MY9/MY11 and GP5+/GP6+, which identify
      more than 40 HPV types. The results failed to identify HPV DNA in the sample,
      although HPV could be readily detected in genomic DNA extracted from paraffin
      embedded condyloma acuminatum, a known HPV-associated lesion. Additionally, we
      tested a VX lesion of the palate for HPV DNA and obtained negative results. Our
      results indicate that VX can arise without HPV infection and suggest other
      possible origins may be involved.

PMID- 15737059
TI  - Cytologic identification of reinke crystalloids in scrapings and imprints of
      fresh testicular tumors: a simple and rapid technique for intraoperative use.
AB  - Although not required for the diagnosis, crystalloids of Reinke are pathognomonic
      for Leydig cell tumor. However, conventional frozen section rarely reveals their
      presence. A method of rapid identification of crystalloids of Reinke could
      improve the intraoperative diagnosis. We tested the efficacy of touch imprints
      and scrape smears for the identification of crystalloids in 2 cases of Leydig
      cell tumor of the testis. Intraoperative smears of the tumors yielded abundant
      crystals. Scrape cytologic testing was the better method. We speculate that the
      process of scraping, and to a lesser extent touch imprinting, disrupts the
      cytoplasm of the Leydig cells and releases the crystalloids. We conclude that
      cytologic testing is an effective method of identifying crystalloids of Reinke in
      Leydig cell tumors of the testis.

PMID- 15737060
TI  - Pathologic quiz case: an 84-year-old woman with a skin cyst containing Ziehl
      Neelsen-positive structures. Basal cell carcinoma associated with a vellus hair
      cyst.

PMID- 15737061
TI  - Pathologic quiz case: a 52-year-old woman with a uterine mass. Leiomyo
      adenomatoid tumor of the uterus.

PMID- 15737062
TI  - Highly nonrandom features of synaptic connectivity in local cortical circuits.
AB  - How different is local cortical circuitry from a random network? To answer this
      question, we probed synaptic connections with several hundred simultaneous
      quadruple whole-cell recordings from layer 5 pyramidal neurons in the rat visual
      cortex. Analysis of this dataset revealed several nonrandom features in synaptic
      connectivity. We confirmed previous reports that bidirectional connections are
      more common than expected in a random network. We found that several highly
      clustered three-neuron connectivity patterns are overrepresented, suggesting that
      connections tend to cluster together. We also analyzed synaptic connection
      strength as defined by the peak excitatory postsynaptic potential amplitude. We
      found that the distribution of synaptic connection strength differs significantly
      from the Poisson distribution and can be fitted by a lognormal distribution. Such
      a distribution has a heavier tail and implies that synaptic weight is
      concentrated among few synaptic connections. In addition, the strengths of
      synaptic connections sharing pre- or postsynaptic neurons are correlated,
      implying that strong connections are even more clustered than the weak ones.
      Therefore, the local cortical network structure can be viewed as a skeleton of
      stronger connections in a sea of weaker ones. Such a skeleton is likely to play
      an important role in network dynamics and should be investigated further.

PMID- 15737063
TI  - Dissociation of cohesin from chromosome arms and loss of arm cohesion during
      early mitosis depends on phosphorylation of SA2.
AB  - Cohesin is a protein complex that is required to hold sister chromatids together.
      Cleavage of the Scc1 subunit of cohesin by the protease separase releases the
      complex from chromosomes and thereby enables the separation of sister chromatids
      in anaphase. In vertebrate cells, the bulk of cohesin dissociates from chromosome
      arms already during prophase and prometaphase without cleavage of Scc1. Polo-like
      kinase 1 (Plk1) and Aurora-B are required for this dissociation process, and Plk1
      can phosphorylate the cohesin subunits Scc1 and SA2 in vitro, consistent with the
      possibility that cohesin phosphorylation by Plk1 triggers the dissociation of
      cohesin from chromosome arms. However, this hypothesis has not been tested yet,
      and in budding yeast it has been found that phosphorylation of Scc1 by the Polo
      like kinase Cdc5 enhances the cleavability of cohesin, but does not lead to
      separase-independent dissociation of cohesin from chromosomes. To address the
      functional significance of cohesin phosphorylation in human cells, we have
      searched for phosphorylation sites on all four subunits of cohesin by mass
      spectrometry. We have identified numerous mitosis-specific sites on Scc1 and SA2,
      mutated them, and expressed nonphosphorylatable forms of both proteins stably at
      physiological levels in human cells. The analysis of these cells lines, in
      conjunction with biochemical experiments in vitro, indicate that Scc1
      phosphorylation is dispensable for cohesin dissociation from chromosomes in early
      mitosis but enhances the cleavability of Scc1 by separase. In contrast, our data
      reveal that phosphorylation of SA2 is essential for cohesin dissociation during
      prophase and prometaphase, but is not required for cohesin cleavage by separase.
      The similarity of the phenotype obtained after expression of nonphosphorylatable
      SA2 in human cells to that seen after the depletion of Plk1 suggests that SA2 is
      the critical target of Plk1 in the cohesin dissociation pathway.

PMID- 15737065
TI  - Predictive spatial dynamics and strategic planning for raccoon rabies emergence
      in Ohio.
AB  - Rabies is an important public health concern in North America because of recent
      epidemics of a rabies virus variant associated with raccoons. The costs
      associated with surveillance, diagnostic testing, and post-exposure treatment of
      humans exposed to rabies have fostered coordinated efforts to control rabies
      spread by distributing an oral rabies vaccine to wild raccoons. Authorities have
      tried to contain westward expansion of the epidemic front of raccoon-associated
      rabies via a vaccine corridor established in counties of eastern Ohio, western
      Pennsylvania, and West Virginia. Although sporadic cases of rabies have been
      identified in Ohio since oral rabies vaccine distribution in 1998, the first
      evidence of a significant breach in this vaccine corridor was not detected until
      2004 in Lake County, Ohio. Herein, we forecast the spatial spread of rabies in
      Ohio from this breach using a stochastic spatial model that was first developed
      for exploratory data analysis in Connecticut and next used to successfully hind
      cast wave-front dynamics of rabies spread across New York. The projections, based
      on expansion from the Lake County breach, are strongly affected by the spread of
      rabies by rare, but unpredictable long-distance translocation of rabid raccoons;
      rabies may traverse central Ohio at a rate 2.5-fold greater than previously
      analyzed wildlife epidemics. Using prior estimates of the impact of local
      heterogeneities on wave-front propagation and of the time lag between
      surveillance-based detection of an initial rabies case to full-blown epidemic,
      specific regions within the state are identified for vaccine delivery and
      expanded surveillance effort.

PMID- 15737064
TI  - Shugoshin prevents dissociation of cohesin from centromeres during mitosis in
      vertebrate cells.
AB  - Cohesion between sister chromatids is essential for their bi-orientation on
      mitotic spindles. It is mediated by a multisubunit complex called cohesin. In
      yeast, proteolytic cleavage of cohesin's alpha kleisin subunit at the onset of
      anaphase removes cohesin from both centromeres and chromosome arms and thus
      triggers sister chromatid separation. In animal cells, most cohesin is removed
      from chromosome arms during prophase via a separase-independent pathway involving
      phosphorylation of its Scc3-SA1/2 subunits. Cohesin at centromeres is refractory
      to this process and persists until metaphase, whereupon its alpha kleisin subunit
      is cleaved by separase, which is thought to trigger anaphase. What protects
      centromeric cohesin from the prophase pathway? Potential candidates are proteins,
      known as shugoshins, that are homologous to Drosophila MEI-S332 and yeast Sgo1
      proteins, which prevent removal of meiotic cohesin complexes from centromeres at
      the first meiotic division. A vertebrate shugoshin-like protein associates with
      centromeres during prophase and disappears at the onset of anaphase. Its
      depletion by RNA interference causes HeLa cells to arrest in mitosis. Most
      chromosomes bi-orient on a metaphase plate, but precocious loss of centromeric
      cohesin from chromosomes is accompanied by loss of all sister chromatid cohesion,
      the departure of individual chromatids from the metaphase plate, and a permanent
      cell cycle arrest, presumably due to activation of the spindle checkpoint.
      Remarkably, expression of a version of Scc3-SA2 whose mitotic phosphorylation
      sites have been mutated to alanine alleviates the precocious loss of sister
      chromatid cohesion and the mitotic arrest of cells lacking shugoshin. These data
      suggest that shugoshin prevents phosphorylation of cohesin's Scc3-SA2 subunit at
      centromeres during mitosis. This ensures that cohesin persists at centromeres
      until activation of separase causes cleavage of its alpha kleisin subunit.
      Centromeric cohesion is one of the hallmarks of mitotic chromosomes. Our results
      imply that it is not an intrinsically stable property, because it can easily be
      destroyed by mitotic kinases, which are kept in check by shugoshin.

PMID- 15737066
TI  - Recombination every day: abundant recombination in a virus during a single multi
      cellular host infection.
AB  - Viral recombination can dramatically impact evolution and epidemiology. In
      viruses, the recombination rate depends on the frequency of genetic exchange
      between different viral genomes within an infected host cell and on the frequency
      at which such co-infections occur. While the recombination rate has been recently
      evaluated in experimentally co-infected cell cultures for several viruses, direct
      quantification at the most biologically significant level, that of a host
      infection, is still lacking. This study fills this gap using the cauliflower
      mosaic virus as a model. We distributed four neutral markers along the viral
      genome, and co-inoculated host plants with marker-containing and wild-type
      viruses. The frequency of recombinant genomes was evaluated 21 d post
      inoculation. On average, over 50% of viral genomes recovered after a single host
      infection were recombinants, clearly indicating that recombination is very
      frequent in this virus. Estimates of the recombination rate show that all regions
      of the genome are equally affected by this process. Assuming that ten viral
      replication cycles occurred during our experiment-based on data on the timing of
      coat protein detection-the per base and replication cycle recombination rate was
      on the order of 2 x 10(-5) to 4 x 10(-5). This first determination of a virus
      recombination rate during a single multi-cellular host infection indicates that
      recombination is very frequent in the everyday life of this virus.

PMID- 15737072
TI  - Biometry, biometrics, biostatistics, bioinformatics,..., bio-X.
AB  - Recent scientific evolutions force us to rethink our profession's position on the
      scientific map, in relation to our neighboring professions, the ones with which
      we traditionally have strong collaborative links as well as the newly emerging
      fields, but also within our own, diverse professional group. We will show that
      great inspiration can be drawn from our own history, in fact from the early days
      of the Society. A recent inspiring example has been set by the late Rob Kempton,
      who died suddenly just months before he was to become President of the
      International Biometric Society.

PMID- 15737070
TI  - A proteomics approach for the identification of nucleophosmin and heterogeneous
      nuclear ribonucleoprotein C1/C2 as chromatin-binding proteins in response to DNA
      double-strand breaks.
AB  - Double-strand breaks (DSBs) of chromosomal DNA trigger the cellular response that
      activates the pathways for DNA repair and cell-cycle checkpoints, and sometimes
      the pathways leading to cell death if the damage is too severe to be tolerated.
      Evidence indicates that, upon generation of DNA DSBs, many nuclear proteins that
      are involved in DNA repair and checkpoints are recruited to chromatin around the
      DNA lesions. In the present study we used a proteomics approach to identify DNA
      damage-induced chromatin-binding proteins in a systematic way. Two-dimensional
      gel analysis for protein extracts of chromatin from DNA-damage-induced and
      control HeLa cells identified four proteins as the candidates for DNA-damage
      induced chromatin-binding proteins. MALDI-TOF (matrix-assisted laser-desorption
      ionization-time-of-flight) MS analysis identified these proteins to be NPM
      (nucleophosmin), hnRNP (heterogeneous nuclear ribonucleoprotein) C1, hnRNP C2 and
      37-kDa laminin-receptor precursor, and the identity of these proteins was further
      confirmed by immunoblot analysis with specific antibodies. We then demonstrated
      with chromatin-binding assays that NPM and hnRNP C1/C2, the abundant nuclear
      proteins with pleiotropic functions, indeed bind to chromatin in a DNA-damage
      dependent manner, implicating these proteins in DNA repair and/or damage
      response. Immunofluorescence experiments showed that NPM, normally present in the
      nucleoli, is mobilized into the nucleoplasm after DNA damage, and that neither
      NPM nor hnRNP C1/C2 is actively recruited to the sites of DNA breaks. These
      results suggest that NPM and hnRNP C1/C2 may function at the levels of the global
      context of chromatin, rather than by specifically targeting the broken DNA.

PMID- 15737073
TI  - Tight clustering: a resampling-based approach for identifying stable and tight
      patterns in data.
AB  - In this article, we propose a method for clustering that produces tight and
      stable clusters without forcing all points into clusters. The methodology is
      general but was initially motivated from cluster analysis of microarray
      experiments. Most current algorithms aim to assign all genes into clusters. For
      many biological studies, however, we are mainly interested in identifying the
      most informative, tight, and stable clusters of sizes, say, 20-60 genes for
      further investigation. We want to avoid the contamination of tightly regulated
      expression patterns of biologically relevant genes due to other genes whose
      expressions are only loosely compatible with these patterns. "Tight clustering"
      has been developed specifically to address this problem. It applies K-means
      clustering as an intermediate clustering engine. Early truncation of a
      hierarchical clustering tree is used to overcome the local minimum problem in K
      means clustering. The tightest and most stable clusters are identified in a
      sequential manner through an analysis of the tendency of genes to be grouped
      together under repeated resampling. We validated this method in a simulated
      example and applied it to analyze a set of expression profiles in the study of
      embryonic stem cells.

PMID- 15737074
TI  - Iterative partial least squares with right-censored data analysis: a comparison
      to other dimension reduction techniques.
AB  - In the linear model with right-censored responses and many potential explanatory
      variables, regression parameter estimates may be unstable or, when the covariates
      outnumber the uncensored observations, not estimable. We propose an iterative
      algorithm for partial least squares, based on the Buckley-James estimating
      equation, to estimate the covariate effect and predict the response for a future
      subject with a given set of covariates. We use a leave-two-out cross-validation
      method for empirically selecting the number of components in the partial least
      squares fit that approximately minimizes the error in estimating the covariate
      effect of a future observation. Simulation studies compare the methods discussed
      here with other dimension reduction techniques. Data from the AIDS Clinical
      Trials Group protocol 333 are used to motivate the methodology.

PMID- 15737075
TI  - Wavelet thresholding with bayesian false discovery rate control.
AB  - The false discovery rate (FDR) procedure has become a popular method for handling
      multiplicity in high-dimensional data. The definition of FDR has a natural
      Bayesian interpretation; it is the expected proportion of null hypotheses
      mistakenly rejected given a measure of evidence for their truth. In this article,
      we propose controlling the positive FDR using a Bayesian approach where the
      rejection rule is based on the posterior probabilities of the null hypotheses.
      Correspondence between Bayesian and frequentist measures of evidence in
      hypothesis testing has been studied in several contexts. Here we extend the
      comparison to multiple testing with control of the FDR and illustrate the
      procedure with an application to wavelet thresholding. The problem consists of
      recovering signal from noisy measurements. This involves extracting wavelet
      coefficients that result from true signal and can be formulated as a multiple
      hypotheses-testing problem. We use simulated examples to compare the performance
      of our approach to the Benjamini and Hochberg (1995, Journal of the Royal
      Statistical Society, Series B57, 289-300) procedure. We also illustrate the
      method with nuclear magnetic resonance spectral data from human brain.

PMID- 15737076
TI  - Model evaluation and spatial interpolation by Bayesian combination of
      observations with outputs from numerical models.
AB  - Constructing maps of dry deposition pollution levels is vital for air quality
      management, and presents statistical problems typical of many environmental and
      spatial applications. Ideally, such maps would be based on a dense network of
      monitoring stations, but this does not exist. Instead, there are two main sources
      of information for dry deposition levels in the United States: one is pollution
      measurements at a sparse set of about 50 monitoring stations called CASTNet, and
      the other is the output of the regional scale air quality models, called Models
      3. A related problem is the evaluation of these numerical models for air quality
      applications, which is crucial for control strategy selection. We develop formal
      methods for combining sources of information with different spatial resolutions
      and for the evaluation of numerical models. We specify a simple model for both
      the Models-3 output and the CASTNet observations in terms of the unobserved
      ground truth, and we estimate the model in a Bayesian way. This provides improved
      spatial prediction via the posterior distribution of the ground truth, allows us
      to validate Models-3 via the posterior predictive distribution of the CASTNet
      observations, and enables us to remove the bias in the Models-3 output. We apply
      our methods to data on SO2 concentrations, and we obtain high-resolution SO2
      distributions by combining observed data with model output. We also conclude that
      the numerical models perform worse in areas closer to power plants, where the SO2
      values are overestimated by the models.

PMID- 15737077
TI  - Modeling association among demographic parameters in analysis of open population
      capture-recapture data.
AB  - We present a hierarchical extension of the Cormack-Jolly-Seber (CJS) model for
      open population capture-recapture data. In addition to recaptures of marked
      animals, we model first captures of animals and losses on capture. The parameter
      set includes capture probabilities, survival rates, and birth rates. The survival
      rates and birth rates are treated as a random sample from a bivariate
      distribution, thus the model explicitly incorporates correlation in these
      demographic rates. A key feature of the model is that the likelihood function,
      which includes a CJS model factor, is expressed entirely in terms of identifiable
      parameters; losses on capture can be factored out of the model. Since the
      computational complexity of classical likelihood methods is prohibitive, we use
      Markov chain Monte Carlo in a Bayesian analysis. We describe an efficient
      candidate-generation scheme for Metropolis-Hastings sampling of CJS models and
      extensions. The procedure is illustrated using mark-recapture data for the moth
      Gonodontis bidentata.

PMID- 15737078
TI  - Genetic susceptibility to prostate, breast, and colorectal cancer among Nordic
      twins.
AB  - To investigate the role of genetics in the development of cancer, we developed a
      new approach to analyze data on prostate, breast, and colorectal cancer from the
      Swedish, Danish, and Finnish twin registries on monozygotic (MZ) and same-sex
      dizygotic (DZ) twins. In the spirit of a sensitivity analysis, we modeled genetic
      inheritance as either an autosomal recessive or dominant cancer susceptibility
      (CS) genotype that involves either a single gene, many genes with equal allele
      frequencies, or three genes with a ninefold range of allele frequencies. We also
      modeled the joint probability of cancer incidence among five age categories,
      conditional on the presence or absence of the CS genotype. The main assumptions
      are: (1) The joint distribution of unobserved environmental effects in a twin
      pair conditional on the presence or absence of the CS genotype is the same for MZ
      and DZ twins, (2) the probability of cancer conditional on the presence or
      absence of the CS genotype and the unobserved environmental effects (i.e., the
      gene-environment interaction) is the same for MZ and DZ twins, and (3) the
      probability of cancer is independent between twins with the CS genotype.
      Estimation was maximum likelihood via a search over allele frequency and two
      levels of EM algorithms. Models had acceptable or good fits. Variability was
      estimated using a bootstrap approach, but only 50 replications were feasible. The
      94th percentile of bootstrap replications for the estimated fraction of cancers
      with the CS genotype ranged, over the various genetic models, from 0.16 to 0.45
      for prostate cancer, 0.12 to 0.30 for breast cancer, and 0.08 to 0.27 for
      colorectal cancer. We conclude that genetic susceptibility makes only a small to
      moderate contribution to the incidence of prostate, breast, and colorectal
      cancer.

PMID- 15737079
TI  - A flexible B-spline model for multiple longitudinal biomarkers and survival.
AB  - Often when jointly modeling longitudinal and survival data, we are interested in
      a multivariate longitudinal measure that may not fit well by linear models. To
      overcome this problem, we propose a joint longitudinal and survival model that
      has a nonparametric model for the longitudinal markers. We use cubic B-splines to
      specify the longitudinal model and a proportional hazards model to link the
      longitudinal measures to the hazard. To fit the model, we use a Markov chain
      Monte Carlo algorithm. We select the number of knots for the cubic B-spline model
      using the Conditional Predictive Ordinate (CPO) and the Deviance Information
      Criterion (DIC). The method and model selection approach are validated in a
      simulation. We apply this method to examine the link between viral load, CD4
      count, and time to event in data from an AIDS clinical trial. The cubic B-spline
      model provides a good fit to the longitudinal data that could not be obtained
      with simple parametric models.

PMID- 15737080
TI  - Multiple imputation for model checking: completed-data plots with missing and
      latent data.
AB  - In problems with missing or latent data, a standard approach is to first impute
      the unobserved data, then perform all statistical analyses on the completed
      dataset--corresponding to the observed data and imputed unobserved data--using
      standard procedures for complete-data inference. Here, we extend this approach to
      model checking by demonstrating the advantages of the use of completed-data model
      diagnostics on imputed completed datasets. The approach is set in the theoretical
      framework of Bayesian posterior predictive checks (but, as with missing-data
      imputation, our methods of missing-data model checking can also be interpreted as
      "predictive inference" in a non-Bayesian context). We consider the graphical
      diagnostics within this framework. Advantages of the completed-data approach
      include: (1) One can often check model fit in terms of quantities that are of key
      substantive interest in a natural way, which is not always possible using
      observed data alone. (2) In problems with missing data, checks may be devised
      that do not require to model the missingness or inclusion mechanism; the latter
      is useful for the analysis of ignorable but unknown data collection mechanisms,
      such as are often assumed in the analysis of sample surveys and observational
      studies. (3) In many problems with latent data, it is possible to check
      qualitative features of the model (for example, independence of two variables)
      that can be naturally formalized with the help of the latent data. We illustrate
      with several applied examples.

PMID- 15737067
TI  - Lineage-specific expansions of retroviral insertions within the genomes of
      African great apes but not humans and orangutans.
AB  - Retroviral infections of the germline have the potential to episodically alter
      gene function and genome structure during the course of evolution. Horizontal
      transmissions between species have been proposed, but little evidence exists for
      such events in the human/great ape lineage of evolution. Based on analysis of
      finished BAC chimpanzee genome sequence, we characterize a retroviral element
      (Pan troglodytes endogenous retrovirus 1 [PTERV1]) that has become integrated in
      the germline of African great ape and Old World monkey species but is absent from
      humans and Asian ape genomes. We unambiguously map 287 retroviral integration
      sites and determine that approximately 95.8% of the insertions occur at non
      orthologous regions between closely related species. Phylogenetic analysis of the
      endogenous retrovirus reveals that the gorilla and chimpanzee elements share a
      monophyletic origin with a subset of the Old World monkey retroviral elements,
      but that the average sequence divergence exceeds neutral expectation for a
      strictly nuclear inherited DNA molecule. Within the chimpanzee, there is a
      significant integration bias against genes, with only 14 of these insertions
      mapping within intronic regions. Six out of ten of these genes, for which there
      are expression data, show significant differences in transcript expression
      between human and chimpanzee. Our data are consistent with a retroviral infection
      that bombarded the genomes of chimpanzees and gorillas independently and
      concurrently, 3-4 million years ago. We speculate on the potential impact of such
      recent events on the evolution of humans and great apes.

PMID- 15737081
TI  - A sample size formula for the supremum log-rank statistic.
AB  - An advantage of the supremum log-rank over the standard log-rank statistic is an
      increased sensitivity to a wider variety of stochastic ordering alternatives. In
      this article, we develop a formula for sample size computation for studies
      utilizing the supremum log-rank statistic. The idea is to base power on the
      proportional hazards alternative, so that the supremum log rank will have the
      same power as the standard log rank in the setting where the standard log rank is
      optimal. This results in a slight increase in sample size over that required for
      the standard log rank. For example, a 5.733% increase occurs for a two-sided test
      having type I error 0.05 and power 0.80. This slight increase in sample size is
      offset by the significant gains in power the supremum log-rank test achieves for
      a wide range of nonproportional hazards alternatives. A small simulation study is
      used for illustration. These results should facilitate the wider use of the
      supremum log-rank statistic in clinical trials.

PMID- 15737082
TI  - Survival model predictive accuracy and ROC curves.
AB  - The predictive accuracy of a survival model can be summarized using extensions of
      the proportion of variation explained by the model, or R2, commonly used for
      continuous response models, or using extensions of sensitivity and specificity,
      which are commonly used for binary response models. In this article we propose
      new time-dependent accuracy summaries based on time-specific versions of
      sensitivity and specificity calculated over risk sets. We connect the accuracy
      summaries to a previously proposed global concordance measure, which is a variant
      of Kendall's tau. In addition, we show how standard Cox regression output can be
      used to obtain estimates of time-dependent sensitivity and specificity, and time
      dependent receiver operating characteristic (ROC) curves. Semiparametric
      estimation methods appropriate for both proportional and nonproportional hazards
      data are introduced, evaluated in simulations, and illustrated using two familiar
      survival data sets.

PMID- 15737083
TI  - Two-sample tests for comparing intra-individual genetic sequence diversity
      between populations.
AB  - Consider a study of two groups of individuals infected with a population of a
      genetically related heterogeneous mixture of viruses, and multiple viral
      sequences are sampled from each person. Based on estimates of genetic distances
      between pairs of aligned viral sequences within individuals, we develop four new
      tests to compare intra-individual genetic sequence diversity between the two
      groups. This problem is complicated by two levels of dependency in the data
      structure: (i) Within an individual, any pairwise distances that share a common
      sequence are positively correlated; and (ii) for any two pairings of individuals
      which share a person, the two differences in intra-individual distances between
      the paired individuals are positively correlated. The first proposed test is
      based on the difference in mean intra-individual pairwise distances pooled over
      all individuals in each group, standardized by a variance estimate that corrects
      for the correlation structure using U-statistic theory. The second procedure is a
      nonparametric rank-based analog of the first test, and the third test contrasts
      the set of subject-specific average intra-individual pairwise distances between
      the groups. These tests are very easy to use and solve correlation problem (i).
      The fourth procedure is based on a linear combination of all possible U
      statistics calculated on independent, identically distributed sequence
      subdatasets, over the two levels (i) and (ii) of dependencies in the data, and is
      more complicated than the other tests but can be more powerful. Although the
      proposed methods are empirical and do not fully utilize knowledge from population
      genetics, the tests reflect biology through the evolutionary models used to
      derive the pairwise sequence distances. The new tests are evaluated theoretically
      and in a simulation study, and are applied to a dataset of 200 HIV sequences
      sampled from 21 children.

PMID- 15737084
TI  - Bayesian adaptive biased-coin designs for clinical trials with normal responses.
AB  - Adaptive designs are used in phase III clinical trials for skewing the allocation
      pattern toward the better treatments. We use optimum design theory to derive a
      skewed Bayesian biased-coin procedure for sequential designs with continuous
      responses. The skewed designs are used to provide adaptive designs, the
      performance of which is studied numerically and theoretically. Important
      properties are loss and the proportion of allocation to the better treatment.

PMID- 15737085
TI  - Bayesian inferences on predictors of conception probabilities.
AB  - Reproductive scientists and couples attempting pregnancy are interested in
      identifying predictors of the day-specific probabilities of conception in
      relation to the timing of a single intercourse act. Because most menstrual cycles
      have multiple days of intercourse, the occurrence of conception represents the
      aggregation across Bernoulli trials for each intercourse day. Because of this
      data structure and dependency among the multiple cycles from a woman,
      implementing analyses has proven challenging. This article proposes a Bayesian
      approach based on a generalization of the Barrett and Marshall model to
      incorporate a woman-specific frailty and day-specific covariates. The model
      results in a simple closed form expression for the marginal probability of
      conception, and has an auxiliary variables formulation that facilitates efficient
      posterior computation. Although motivated by fecundability studies, the approach
      can be used for efficient variable selection and model averaging in general
      applications with categorical or discrete event time data.

PMID- 15737086
TI  - Multi-list methods using incomplete lists in closed populations.
AB  - Multi-list methods have become a common application of capture-recapture
      methodology to estimate the size of human populations, and have been successfully
      applied to estimating prevalence of diabetes, human immunodeficiency virus (HIV),
      and drug abuse. A key assumption in multi-list methods is that individuals have a
      unique "tag" that allows them to be matched across all lists. This article
      develops multi-list methodology that relaxes the assumption of a single tag
      common to all lists. Estimates are found using estimating functions. An example
      illustrates its application for estimating the prevalence of diabetes, and a
      simulation study investigates conditions under which the methodology is robust to
      different list and population sizes.

PMID- 15737087
TI  - A Markov chain model for animal estrous cycling data.
AB  - Estrous cycling data contain sequences of characters (e.g., DPEMD). Each sequence
      represents an animal's estrous cycle, with each character indicating the daily
      estrous cycle stage. Changes in the estrous cycle pattern, which is determined by
      estrous stage lengths, can provide information on adverse events. Stage lengths
      are not directly observable. However interval censored lengths for all but the
      first and the last stages in a sequence can be extracted from the data. We
      propose a Markov chain model to approximate the estrous cycling process. The
      transition probabilities from one stage to another can be derived by conditioning
      on stage lengths. Assuming Weibull distribution for stage lengths, with the
      second Weibull parameter depending upon treatment effects and animal-specific
      random effects, regression models on censored stage lengths are fitted. A
      Bayesian approach is used for inference on dose effects. The analysis is
      implemented with MCMC method in WinBUGS. An estrous cycling data set from a
      National Toxicology Program study is analyzed as an example.

PMID- 15737088
TI  - Quantile regression models with multivariate failure time data.
AB  - As an alternative to the mean regression model, the quantile regression model has
      been studied extensively with independent failure time data. However, due to
      natural or artificial clustering, it is common to encounter multivariate failure
      time data in biomedical research where the intracluster correlation needs to be
      accounted for appropriately. For right-censored correlated survival data, we
      investigate the quantile regression model and adapt an estimating equation
      approach for parameter estimation under the working independence assumption, as
      well as a weighted version for enhancing the efficiency. We show that the
      parameter estimates are consistent and asymptotically follow normal
      distributions. The variance estimation using asymptotic approximation involves
      nonparametric functional density estimation. We employ the bootstrap and
      perturbation resampling methods for the estimation of the variance-covariance
      matrix. We examine the proposed method for finite sample sizes through simulation
      studies, and illustrate it with data from a clinical trial on otitis media.

PMID- 15737089
TI  - Robust estimation of multivariate covariance components.
AB  - In many settings, such as interlaboratory testing, small area estimation in
      sample surveys, and heritability studies, investigators are interested in
      estimating covariance components for multivariate measurements. However, the
      presence of outliers can seriously distort estimates obtained using standard
      procedures such as maximum likelihood. We propose a procedure based on M
      estimation for robustly estimating multivariate covariance components in the
      presence of outliers; the procedure applies to balanced and unbalanced data. We
      present an algorithm for computing the robust estimates and examine the
      performance of the estimator through a simulation study. The estimator is used to
      find covariance components and identify outliers in a study of variability of egg
      length and breadth measurements of American coots.

PMID- 15737090
TI  - Semiparametric estimation of proportional mean residual life model in presence of
      censoring.
AB  - A mean residual life function is the average remaining life of a surviving
      subject, as it varies with time. The proportional mean residual life model was
      proposed by Oakes and Dasu (1990, Biometrika77, 409-410) in regression analysis
      to study its association with related covariates in absence of censoring. In this
      article, we develop some semiparametric estimation procedures to take censoring
      into account. The proposed methodology is evaluated via simulation studies, and
      further applied to a clinical trial of chemotherapy in postoperative radiotherapy
      of lung cancer patients.

PMID- 15737091
TI  - Bias-corrected maximum likelihood estimator of the negative binomial dispersion
      parameter.
AB  - We derive a first-order bias-corrected maximum likelihood estimator for the
      negative binomial dispersion parameter. This estimator is compared, in terms of
      bias and efficiency, with the maximum likelihood estimator investigated by
      Piegorsch (1990, Biometrics46, 863-867), the moment and the maximum extended
      quasi-likelihood estimators investigated by Clark and Perry (1989, Biometrics45,
      309-316), and a double-extended quasi-likelihood estimator. The bias-corrected
      maximum likelihood estimator has superior bias and efficiency properties in most
      instances. For ease of comparison we give results for the two-parameter negative
      binomial model. However, an example involving negative binomial regression is
      given.

PMID- 15737092
TI  - Genomic control for association studies under various genetic models.
AB  - Case-control studies are commonly used to study whether a candidate allele and a
      disease are associated. However, spurious association can arise due to population
      substructure or cryptic relatedness, which cause the variance of the trend test
      to increase. Devlin and Roeder derived the appropriate variance inflation factor
      (VIF) for the trend test and proposed a novel genomic control (GC) approach to
      estimate VIF and adjust the test statistic. Their results were derived assuming
      an additive genetic model and the corresponding VIF is independent of the
      candidate allele frequency. We determine the appropriate VIFs for recessive and
      dominant models. Unlike the additive test, the VIFs for the optimal tests for
      these two models depend on the candidate allele frequency. Simulation results
      show that, when the null loci used to estimate the VIF have allele frequencies
      similar to that of the candidate gene, the GC tests derived for recessive and
      dominant models remain optimal. When the underlying genetic model is unknown or
      the null loci and candidate gene have quite different allele frequencies, the GC
      tests derived for the recessive or dominant models cannot be used while the GC
      test derived for the additive model can be.

PMID- 15737093
TI  - A queueing model for chronic recurrent conditions under panel observation.
AB  - In many chronic conditions, subjects alternate between an active and an inactive
      state, and sojourns into the active state may involve multiple lesions,
      infections, or other recurrences with different times of onset and resolution. We
      present a biologically interpretable model of such chronic recurrent conditions
      based on a queueing process. The model has a birth-death process describing
      recurrences and a semi-Markov process describing the alternation between active
      and inactive states, and can be fit to panel data that provide only a binary
      assessment of the active or inactive state at a series of discrete time points
      using a hidden Markov approach. We accommodate individual heterogeneity and
      covariates using a random effects model, and simulate the posterior distribution
      of unknowns using a Markov chain Monte Carlo algorithm. Application to a clinical
      trial of genital herpes shows how the method can characterize the biology of the
      disease and estimate treatment efficacy.

PMID- 15737094
TI  - A stochastic model to analyze clonal data on multi-type cell populations.
AB  - This article presents a stochastic model designed to analyze experimental data on
      the development of cell clones composed of two (or more) distinct types of cells.
      The proposed model is an extension of the traditional multi-type Bellman-Harris
      branching stochastic process allowing for nonidentical time-to-transformation
      distributions defined for different cell types. A simulated pseudo likelihood
      method has been developed for the parametric statistical inference from
      experimental data on cell clones under the proposed model. The method uses
      simulation-based approximations of the means and the variance-covariance matrices
      of cell counts. The proposed estimator for the vector of unknown parameters is
      strongly consistent and asymptotically normal under mild regularity conditions,
      while its variance-covariance matrix is estimated by the parametric bootstrap. A
      Monte Carlo Wald test is proposed for the test of hypotheses. Finite sample
      properties of the estimator have been studied by computer simulations. The model
      and associated methods of parametric inference have been applied to the analysis
      of proliferation and differentiation of cultured O-2A progenitor cells that play
      a key role in the development of the central nervous system. It follows from this
      analysis that the time to division of the progenitor cell and the time to its
      differentiation (into an oligodendrocyte) are not identically distributed. This
      biological finding suggests that a molecular event determining the type of cell
      transformation is more likely to occur at the start rather than at the end of the
      mitotic cycle.

PMID- 15737095
TI  - A class of Bayesian shared gamma frailty models with multivariate failure time
      data.
AB  - For multivariate failure time data, we propose a new class of shared gamma
      frailty models by imposing the Box-Cox transformation on the hazard function, and
      the product of the baseline hazard and the frailty. This novel class of models
      allows for a very broad range of shapes and relationships between the hazard and
      baseline hazard functions. It includes the well-known Cox gamma frailty model and
      a new additive gamma frailty model as two special cases. Due to the nonnegative
      hazard constraint, this shared gamma frailty model is computationally challenging
      in the Bayesian paradigm. The joint priors are constructed through a conditional
      marginal specification, in which the conditional distribution is univariate, and
      it absorbs the nonlinear parameter constraints. The marginal part of the prior
      specification is free of constraints. The prior distributions allow us to easily
      compute the full conditionals needed for Gibbs sampling, while incorporating the
      constraints. This class of shared gamma frailty models is illustrated with a real
      dataset.

PMID- 15737096
TI  - Two-dimensional dose finding in discrete dose space.
AB  - The objective of a Phase I trial with two agents is to find a set of maximum
      tolerated dose combinations that yield a prespecified toxicity rate. In this
      article, we consider the case where several doses of one agent are fixed and the
      goal is to find the maximum-tolerated dose of the other agent to be used in
      combination with each of the doses of agent one. We propose a Bayesian design
      that uses a parsimonious working model for the dose-toxicity relationship. We
      show that the new design is more effective in identifying the maximum-tolerated
      combinations than one-dimensional designs applied at each dose level of one of
      the agents.

PMID- 15737097
TI  - Regression modeling of competing risks data based on pseudovalues of the
      cumulative incidence function.
AB  - Typically, regression models for competing risks outcomes are based on
      proportional hazards models for the crude hazard rates. These estimates often do
      not agree with impressions drawn from plots of cumulative incidence functions for
      each level of a risk factor. We present a technique which models the cumulative
      incidence functions directly. The method is based on the pseudovalues from a
      jackknife statistic constructed from the cumulative incidence curve. These
      pseudovalues are used in a generalized estimating equation to obtain estimates of
      model parameters. We study the properties of this estimator and apply the
      technique to a study of the effect of alternative donors on relapse for patients
      given a bone marrow transplant for leukemia.

PMID- 15737098
TI  - Bayesian population dynamics of interacting species: great gerbils and fleas in
      Kazakhstan.
AB  - We propose a discrete-time Bayesian hierarchical model for the population
      dynamics of the great gerbil-flea ecological system. The model accounts for the
      sampling variability arising from data originally collected for other purposes.
      The prior for the unknown population densities incorporates specific biological
      hypotheses regarding the interacting dynamics of the two species, as well as
      their life cycles, where density-dependent effects are included. Posterior
      estimates are obtained via Markov chain Monte Carlo. The variance of the observed
      density estimates is a quadratic function of the unknown density. Our study
      indicates the presence of a density-dependent growth rate for the gerbil
      population. For the flea population there is clear evidence of density-dependent
      over-summer net growth, which is dependent on the flea-to-gerbil ratio at the
      beginning of the reproductive summer. Over-winter net growth is favored by high
      density. We estimate that on average 35% of the gerbil population survives the
      winter. Our study shows that hierarchical Bayesian models can be useful in
      extracting ecobiological information from observational data.

PMID- 15737099
TI  - Bayesian monitoring of clinical trials with failure-time endpoints.
AB  - This article presents an aid for monitoring clinical trials with failure-time
      endpoints based on the Bayesian nonparametric analyses of the data. The posterior
      distribution is a mixture of Dirichlet processes in the presence of censoring if
      one assumes a Dirichlet process prior for the survival distribution. Using Gibbs
      sampling, one can generate random samples from the posterior distribution. With
      samples from the posterior distributions of treatment-specific survival curves,
      one can evaluate the current evidence in favor of stopping or continuing the
      trial based on summary statistics of these survival curves. Because the method is
      nonparametric, it can easily be used, for example, in situations where hazards
      cross or are suspected to cross and where relevant clinical decisions might be
      based on estimating when the integral between the curves might be expected to
      become positive and in favor of the new but toxic therapy. An example based on an
      actual trial illustrates the method.

PMID- 15737100
TI  - Attributable effects in case2-studies.
AB  - In an effort to determine whether a particular treatment causes a particular
      outcome event, data are obtained from a database system that records events when
      they occur, and for such events, the system records exposure to the treatment.
      That is, the system records information about cases. The system provides no
      information about events that might have occurred but did not, that is, about
      units which are not cases. Roughly speaking, we know the number of successes for
      two proportions, treated and control, but not the numbers of trials or units for
      these proportions; indeed, the concept of a "trial" may be somewhat vague. With
      no further information, the situation is quite hopeless. However, an interesting
      strategy that is sometimes used entails identifying two types of cases whose
      origin is entirely different so that it is known the cases of the second type
      were definitely not affected by the treatment under study. This strategy--the
      case-case or case2-study--seems to have been reinvented independently many times,
      and has recently been offered as a general strategy for infectious disease
      epidemiology by McCarthy and Giesecke (1999, International Journal of
      Epidemiology 28, 764-768). Can this strategy permit estimation of the number of
      cases caused by the treatment? Using attributable effects in a new way, a method
      of exact inference is proposed, along with a large sample approximation. Two
      examples are discussed: one concerning the effects of daytime running lights
      (DRLs) on the risk of multivehicle accidents; the other concerning the origin of
      a Salmonella infection. A counterexample with superficially similar appearance is
      also discussed concerning suicide rates following the publication of Final Exit;
      here, the treatment may alter the outcome, or it may alter the type, and the
      attributable effect cannot be estimated.

PMID- 15737101
TI  - Comparison of maximum statistics for hypothesis testing when a nuisance parameter
      is present only under the alternative.
AB  - In many practical problems, a hypothesis testing involves a nuisance parameter
      which appears only under the alternative hypothesis. Davies (1977, Biometrika 64,
      247-254) proposed the maximum of the score statistics over the whole range of the
      nuisance parameter as a test statistic for this type of hypothesis testing.
      Freidlin, Podgor, and Gastwirth (1999, Biometrics 55, 883-886) studied two other
      simpler maximum test statistics, the maximum of the score statistics at two
      extreme points of the nuisance parameter, and the maximum of the score statistics
      at three points of the nuisance parameter including the two extreme points. In
      this article, we compare the powers of these three maximum-type statistics in the
      context of three genetic problems.

PMID- 15737102
TI  - Assessing accuracy of mammography in the presence of verification bias and
      intrareader correlation.
AB  - The performance of a medical diagnostic test is often evaluated by comparing the
      outcome of the test to the patient's true disease state. Receiver operating
      characteristic analysis may then be used to summarize test accuracy. However,
      such analysis may encounter several complications in actual practice. One
      complication is verification bias, i.e., gold standard assessment of disease
      status may only be partially available and the probability of ascertainment of
      disease may depend on both the test result and characteristics of the subject. A
      second issue is that tests interpreted by the same rater may not be independent.
      Using estimating equations, we generalize previous methods that address these
      problems. We contrast the performance of alternative estimators of accuracy using
      robust sandwich variance estimators to permit valid asymptotic inference. We
      suggest that in the context of an observational cohort study where rich covariate
      information is available, a weighted estimating equations approach may be
      preferable for its robustness against model misspecification. We apply the
      methodology to mammography as performed by community radiologists.

PMID- 15737103
TI  - Closure procedures for monotone bi-factorial dose-response designs.
AB  - Two goals of multiple-dose factorial trials are (i) demonstrating improved
      effectiveness of a fixed combination over each of its components as well as (ii)
      identifying a safe and effective dose range. The authors address both goals
      though with focus on the second by closure procedures that guarantee strong
      control of the familywise error rate. Two different families of null hypotheses
      are investigated for bi-factorial dose-response designs that are monotone with
      respect to the matrix partial order. One is suitable to find the minimum
      effective dose(s) and the other one is large enough to identify the highest
      effective dose step(s). Likelihood ratio tests and appropriate multiple contrast
      tests are applied to an unbalanced clinical trial example taken from Hung (2000,
      Statistics in Medicine 19, 2079-2087). Full computer code written in the R
      language is available from the Internet.

PMID- 15737104
TI  - Multiplicity-adjusted inferences in risk assessment: benchmark analysis with
      quantal response data.
AB  - A primary objective in quantitative risk or safety assessment is characterization
      of the severity and likelihood of an adverse effect caused by a chemical toxin or
      pharmaceutical agent. In many cases data are not available at low doses or low
      exposures to the agent, and inferences at those doses must be based on the high
      dose data. A modern method for making low-dose inferences is known as benchmark
      analysis, where attention centers on the dose at which a fixed benchmark level of
      risk is achieved. Both upper confidence limits on the risk and lower confidence
      limits on the "benchmark dose" are of interest. In practice, a number of possible
      benchmark risks may be under study; if so, corrections must be applied to adjust
      the limits for multiplicity. In this short note, we discuss approaches for doing
      so with quantal response data.

PMID- 15737105
TI  - Extending McNemar's test: estimation and inference when paired binary outcome
      data are misclassified.
AB  - McNemar's test is popular for assessing the difference between proportions when
      two observations are taken on each experimental unit. It is useful under a
      variety of epidemiological study designs that produce correlated binary outcomes.
      In studies involving outcome ascertainment, cost or feasibility concerns often
      lead researchers to employ error-prone surrogate diagnostic tests. Assuming an
      available gold standard diagnostic method, we address point and confidence
      interval estimation of the true difference in proportions and the paired-data
      odds ratio by incorporating external or internal validation data. We distinguish
      two special cases, depending on whether it is reasonable to assume that the
      diagnostic test properties remain the same for both assessments (e.g., at
      baseline and at follow-up). Likelihood-based analysis yields closed-form
      estimates when validation data are external and requires numeric optimization
      when they are internal. The latter approach offers important advantages in terms
      of robustness and efficient odds ratio estimation. We consider internal
      validation study designs geared toward optimizing efficiency given a fixed cost
      allocated for measurements. Two motivating examples are presented, using gold
      standard and surrogate bivariate binary diagnoses of bacterial vaginosis (BV) on
      women participating in the HIV Epidemiology Research Study (HERS).

PMID- 15737106
TI  - Applying concepts of generalizability theory on clinical trial data to
      investigate sources of variation and their impact on reliability.
AB  - This work aims at applying concepts of generalizability theory to data resulting
      from clinical trials. The focus is to study the sources of variance and their
      impact on the reliability and generalizability of a psychiatric measurement
      scale. The goal is to identify, measure, and thereby potentially find strategies
      to reduce the influence of these sources on the measurement in question for
      future trials. This approach was originally devised by Cronbach and his
      associates and is known as generalizability theory. This work shows how full
      modeling power in mixed models can be used to study generalizability using data
      from five double-blind randomized clinical trials, comparing the effects of
      risperidone to conventional antipsychotic agents for the treatment of chronic
      schizophrenia.

PMID- 15737107
TI  - An estimator for treatment comparisons among survivors in randomized trials.
AB  - In clinical trials of advanced-stage disease it is often of interest to perform
      treatment comparisons for endpoints which are defined only for survivors.
      Examples include time on ventilation in ventilation studies, change in quality of
      life in health-related quality-of-life studies, and duration of response to
      therapy in therapeutic trials. Randomized treatment comparisons for these
      endpoints cannot be performed because the outcomes are only defined in the
      nonrandomly selected subgroup of survivors. We propose a new evaluation of the
      survivor average causal effect (SACE) for treatment comparisons of this nature.
      We provide an estimator of SACE in the presence of no unmeasured confounders, a
      nontestable assumption, which identifies SACE. We also outline a sensitivity
      analysis for exploring robustness of conclusions to deviations from this
      assumption. We apply this method to duration of ventilation in a clinical trial
      of acute respiratory distress syndrome.

PMID- 15737123
TI  - Evaluating the accuracy of Malformations Surveillance Program in detecting
      virilization due to congenital adrenal hyperplasia.
AB  - Malformations surveillance programs of newborn infants have been developed as a
      method for identifying serious and relatively common birth defects. The
      virilization of newborn infants with the classic 21-hydroxylase form of
      congenital adrenal hyperplasia must be identified early if the associated
      metabolic crisis in the perinatal period is to be prevented. We compared the
      detection of virilization associated with 21-hydroxylase congenital adrenal
      hyperplasia in infants by three methods: an 'active' malformations surveillance
      of medical records at a large urban hospital; routine medical care by examining
      physicians; and newborn biochemical screening of blood samples. The experience at
      a large maternity center in Boston, since 1972, showed that pediatricians often
      recognized affected females (6/6), but not males (0/2); the state newborn
      screening program, begun in 1990, identified correctly all affected males and
      females. The Active Malformations Surveillance Program was the least effective
      screening method, identifying four of six affected females and neither of the
      affected males. The low rate of detecting affected females by the Surveillance
      Program was attributed to a failure to sensitize the research assistants to the
      importance of physicians' notations regarding the signs and symptoms of
      virilization. The failure of examining physicians, and thereby, the malformations
      surveillance program, to detect virilized newborn males was due to the lack of
      consistent associated physical features. These comparisons between these three
      methods of detection can be used to design and improve malformations surveillance
      programs.

PMID- 15737124
TI  - Population-based case-control study of oral ketoconazole treatment for birth
      outcomes.
AB  - The objective of the study presented here was to check the effect of oral
      ketoconazole treatment on fetal development. Ketoconazole has been given a
      teratogenic classification of C by the US Food and Drug Administration, but human
      controlled epidemiological studies of the treatment's effects have not been
      reported. The occurrence of ketoconazole use in the second to third months of
      gestation was compared between cases with congenital abnormalities and their
      matched controls in the large population-based data set of the Hungarian Case
      Control Surveillance of Congenital Abnormalities, 1980-1996. Birth weight and
      gestational age were evaluated in control newborn infants born to mothers with or
      without ketoconazole treatment. The case group comprised 22,843 cases with
      congenital abnormalities, while the control group contained 38,151 newborn
      infants without any defects. Six infants (0.03%) and 12 controls (0.03%) had
      mothers who had received oral ketoconazole treatment (prevalence odds ratio: with
      95% confidence interval: 0.8, 0.3-2.2). No group of infants with congenital
      abnormalities had mothers with a higher incidence of use of the drug. The mean
      gestational age was somewhat longer while birth weight was somewhat larger in
      controls with ketoconazole treated mothers. Our study failed to demonstrate a
      higher rate of congenital abnormalities in infants with mothers who had received
      oral ketoconazole treatment during pregnancy.

PMID- 15737125
TI  - Experimental cortical dysplasia following ibotenate administration in hamsters:
      pathogenesis of microgyria and associated gray matter heterotopia.
AB  - The study presented here investigated the pathogenetic relationship among
      different types of neuronal migration disorders occurring simultaneously in the
      brain using an experimental model induced by ibotenate in hamsters. In the
      cerebral cortex, abnormal neuronal arrangement was induced 1 day after ibotenate
      injection. This brain lesion resulted in microgyria in the rostral portion, focal
      subcortical heterotopia in the mid-portion, and focal subependymal heterotopia in
      the caudal portion in the same specimen. Vimentin-immunoreactive radial glial
      fibers were lacking in the area of disorganized neuronal arrangement, but were
      detected around the microgyria and the intermediate zone surrounding focal
      subcortical heterotopia. The focal subependymal heterotopia did not include
      radial glial elements. Glial fibrillary acidic protein (GFAP)-positive glial
      reaction was weak in these cortical lesions. We suggest that the occurrence of
      each type of migration disorder depends on the depth of the cortical lesion, that
      is, the production of microgyria, focal subcortical heterotopia and focal
      subependymal heterotopia are closely related to the lesions including the
      cortical plate, subplate and ventricular zone, respectively.

PMID- 15737126
TI  - Neuropathological examination of fetal rat brain in the 5-bromo-2'-deoxyuridine
      induced neurodevelopmental disorder model.
AB  - The majority of prior developmental neurotoxicity studies focused on postnatal
      subjects rather than on the fetus. In the present paper, we demonstrate the use
      of histological examination of fetal rat (embryonic day 16.5) brain serial
      sections, employing Nissl staining and microtubule-associated protein 2 (MAP2)
      immunohistochemistry, in evaluating a chemical-induced neurodevelopmental
      disorder. Since prenatal treatment with 5-bromo-2'-deoxyuridine (BrdU) is known
      to induce behavioral abnormalities such as locomotor hyperactivity in offspring,
      pregnant rats were administered 50 mg/kg on gestation days 9.5 through 15.5. The
      fetal brains at embryonic day 16.5 were collected and processed for
      neuropathological study. Cell death, including DNA strand breaks, was observed in
      specific areas of the fetal brain such as the neuroepithelium, intermediate zone
      and/or differentiating zones (e.g. neocortex and striatum) in exposed fetuses. In
      addition, the neocortex had an abnormal appearance cortical plate, which was also
      detected by MAP2 immunohistochemistry. The abnormal cortical plate was observed
      consistently, while the grade of cell death was generally very mild and variable.
      No significant alteration was detected in the brainstem. The present study
      reveals that histological observation of the fetal brain includes sensitive
      endpoints in developmental neurotoxicity, and that BrdU, at a dose generally
      administered to label proliferating cells, affects the development of the fetal
      neocortex.

PMID- 15737127
TI  - Parental origin and cell stage of non-disjunction of double trisomy in
      spontaneous abortion.
AB  - Using polymorphic analysis of microsatellites, we investigated the parental
      origin and mechanism of double trisomies seen in cases of spontaneous abortion.
      We obtained chorionic villi from spontaneous abortions, and peripheral blood from
      females who experienced abortion and their spouses. Chromosomal analysis of 170
      cases revealed four cases with double trisomy. The karyotypes of these cases are
      48,XX,+16,+22, 48,XXY,+18, 48,XX,+15,+21 and 48,XX,+2,+5. In the present study,
      the incidence of double trisomy was 2.4% of spontaneous abortions. Polymorphic
      analysis of microsatellites indicated that extra chromosomes were all of maternal
      origin in the four cases of double trisomy. The predominance of maternal origin
      in cases of double trisomy is similar to cases of single trisomy. The result also
      indicated that both extra chromosomes in two cases occurred by non-disjunction at
      the first meiotic division, and extra chromosomes in the other two cases occurred
      by non-disjunction at the first mitotic division. The mean maternal age in cases
      of double trisomy was significantly higher than that in cases of single trisomy.
      These findings suggest the possibility that abnormal separation of two or more
      chromosomes may occur simultaneously in oogonia, and that this phenomenon may
      increase in relation to the increase in age of women.

PMID- 15737128
TI  - Basic investigation of the lectin method for separation and recovery of nucleated
      red blood cells in maternal blood, and a study into the frequency of nucleated
      red blood cells in fetomaternal disorders.
AB  - We previously reported the separation and recovery of nucleated red blood cells
      (NRBCs) in maternal blood using the lectin method. In the present study, we
      verified the lectin method and investigated the appearance of NRBCs during
      pregnancy. For the concentration of lectin soy bean agglutinin, 7 mL of maternal
      peripheral blood was collected from 20 subjects, and the relative fluorescence
      intensity was measured using flowcytometry; 50 mg/mL, used in previous studies,
      was the optimal concentration. The number of cells recovered at each step of the
      lectin method was also investigated by FACS using fluorescence-labeled CD11a and
      CD33, and the results showed the usefulness of the method. Next, 7 mL of maternal
      peripheral blood was collected from 292 women with a normal single pregnancy (389
      specimens), and NRBCs were separated and recovered using the lectin method. NRBCs
      slightly increased over the course of pregnancy (y = 4.29x + 5.03, r2 = 0.11).
      When blood was collected multiple times in the same subjects, NRBCs increased in
      63 of 77 subjects (83.1%, percent change: 2.4 +/- 19.0). No NRBCs were recovered
      in 17 subjects (4.7%). Regarding the relationship between fetomaternal disorders
      and the frequency of NRBCs, 89.4 +/- 92.6 cells appeared per 10 mL of maternal
      blood in the normal group, but NRBCs increased in patients with 18 trisomy,
      placenta previa, pre-eclampsia, intrauterine fetal death, and 21 trisomy. NRBC
      examination may play an assisting role not only in fetal diagnosis but also in
      fetomaternal diagnosis.

PMID- 15737129
TI  - Improved technique for fetal heart examination in developmental toxicity studies
      in rats.
AB  - Bouin's or a 10% formalin solution has been used to fixate internal fetal
      observations for developmental toxicity studies in rats. However, these fixatives
      are known to cause contraction of the ventricle of the heart and arteries, which
      makes dissection and observation more difficult. Fetuses on day 20 of gestation
      from pregnant Crj:CD(SD)IGS rats were injected with 10 w/v% magnesium chloride/10
      vol% neutral buffered formalin solution into the thoracic cavity, and then fixed
      in 10 vol% neutral buffered formalin. After fixation, the heart was dissected
      using a modified Staples technique. In treated fetuses, the membranous region of
      the ventricular septum and the valves were clearly observed in an expanded state.
      We conclude that this method increases the ability to detect heart anomalies and
      decreases the chance of a false-positive finding.

PMID- 15737130
TI  - Deletion involving the TWIST locus and the HOXA cluster: a contiguous gene
      syndrome on 7p?
AB  - Deletion of TWIST on 7p21 leads to Saethre-Chotzen syndrome, whereas deletion of
      the HOXA cluster on 7p15.2 leads to hand-foot-genital syndrome. We report here a
      patient with 46,XY,del(7)(p15.2p21) who had craniosynostosis, maxillary
      hypoplasia, prominent ear crus, rectoperineal fistula, and hypoplastic fifth
      fingers. Using fluorescence in situ hybridization, we demonstrated the deletion
      to encompass the TWIST locus and the HOXA cluster. We suggest that many, if not
      all, of the features of this patient could be accounted for by combined
      haploinsufficiency of the TWIST and HOXA cluster. Hence, the patient's phenotype
      may define a new contiguous gene syndrome on 7p.

PMID- 15737132
TI  - Twin dilemmas for medical education.

PMID- 15737133
TI  - Percutaneous carotid artery stenting: a strategy in evolution.
AB  - BACKGROUND: Carotid stenting was initially proposed as an alternative to surgical
      endarterectomy for selected high-risk patients. More recently, patients of
      standard surgical risk are being considered for percutaneous treatment of their
      carotid disease. AIMS: To describe the clinical outcomes of an initial
      consecutive cohort of patients treated by carotid stenting at one institution.
      METHODS: Between December 1997 and July 2003, 111 patients underwent stenting of
      118 carotid arteries. Peri-procedural and long-term outcome data were collected.
      RESULTS: Most patients (>70%) were high-risk candidates for endarterectomy.
      Stents were successfully placed in 117/118 carotid arteries (99.2%). Distal
      protection devices were used in 43/118 (36.4%). The peri-procedural rate of death
      or disabling stroke was 3/118 (2.5%). Death or any stroke occurred in 11/118
      (9.3%). However, only 7/118 (5.9%) procedures resulted in death or any persistent
      stroke (neurological deficit >1 week post-procedure). No myocardial infarction
      occurred. Median length of post-procedure hospitalization was 1 day. Long-term
      follow up was possible for 101 patients (91.0%) over a mean period of 27.1
      months. The Kaplan-Meier estimate of survival free of ipsilateral stroke 36 and
      66 months after carotid stenting was 77.0 +/- 9.5% and 68.2 +/- 15.1%,
      respectively. The estimated survival free of any stroke or stent failure was 70.9
      +/- 10.7% and 60.7 +/- 17.4%, respectively. The majority of late deaths (7/11)
      were due to cardiac disease. CONCLUSION: We conclude that stenting of carotid
      stenoses is feasible, with a high procedural success rate and low complication
      rate. Carotid stenting should be considered the procedure of choice for high-risk
      patients.

PMID- 15737134
TI  - Implementing evidence-based guidelines:inpatient management of chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Evidence-based guidelines exist to guide inpatient management of
      chronic obstructive pulmonary disease (COPD) exacerbations, but we do not know
      how well these recommendations are adhered to. AIMS: The aims of this study were:
      (i) to examine concordance with evidence based guidelines for inpatient
      management of COPD and (ii)to address deficiencies in compliance with guidelines
      by feedback of audit results and distribution of an education package. METHODS:
      Retrospective chart reviews were performed using a data collection tool based on
      current guidelines. Forty-nine consecutive COPD admissions were audited, and
      results presented to medical staff. An education package was distributed directly
      after the presentation. One month later,35 consecutive separations were reviewed.
      Concordance with recommendations supported by the highest level of evidence was
      calculated. RESULTS: Data were complete for 84 cases. Concordance rates ranged
      from 0 to 100%. Apart from initiation of systemic steroids (80-83%)and avoidance
      of intravenous aminophylline (100%),concordance rates were less than 60%. The
      only significant improvement post-intervention was for steroid duration (10 vs
      29%,95% confidence interval for difference (-36.2, -1.8)). CONCLUSION:
      Recommendations for steroid initiation and avoidance of aminophylline are well
      adhered to. Concordance rates for other recommendations were generally less than
      60%. Concordance with recommendations for steroid duration was significantly
      improved by our intervention. The findings suggest that to facilitate evidence
      based practice, alternative interventions should be evaluated.

PMID- 15737136
TI  - Clinical practice guidelines: barriers to durability after effective early
      implementation.
AB  - BACKGROUND: Clinical practice guidelines in general (General-CPG) may reduce
      variation in clinician performance and improve patient outcomes. Short-term
      evaluation is now routine, but demonstration of early successful implementation
      does not necessarily ensure longer-term effectiveness. AIM: To assess adherence
      to chronic obstructive pulmonary disease (COPD)-CPG recommendations at the Royal
      Melbourne Hospital (RMH), 2 years after successful implementation. To identify
      barriers to sustained success of General-CPG. METHODS: A multi-faceted evaluation
      was performed to document: (i) current adherence to COPD management
      recommendations (medical record audit); (ii) awareness of attitudes towards and
      barriers for the use of COPD-CPG and General-CPG (staff survey, focus groups and
      key informant interviews) and (iii) access to and quality of available General
      CPG (internet review and random sample General-CPG evaluation. RESULTS: Adherence
      to COPD-CPG recommendations was highly variable. Adherence was higher in the
      Emergency Department than the general wards and for specific therapeutic
      recommendations. It was lower for non-pharmacological therapy and for
      recommendations relating to processes of care. Most health professionals were in
      favour of General-CPG. Barriers to use of General-CPG were in keeping with
      previous literature reports. Organizational issues including high levels of staff
      turnover and lack of integration of General-CPG into hospital quality frameworks
      were highlighted as major barriers. Hospital intranet access and presentation of
      General-CPG identified lack of consistency in terminology and presentation.
      CONCLUSION: Short-term effectiveness of COPD-CPG implementation did not ensure
      sustained success. Departmental organizational behaviours and organizational
      system barriers are major factors influencing durability.

PMID- 15737135
TI  - Enzyme replacement therapy for Gaucher disease in Australia.
AB  - AIM: To study the effectiveness of a specific national programme of enzyme
      replacement therapy (ERT) for patients with severe forms of Gaucher disease, a
      disorder of sphingolipid metabolism resulting from an inherited deficiency of the
      lysosomal enzyme beta-Glucocerebrosidase. METHODS: Prospective analysis of data
      submitted at entry and every 6 months on therapy. The responses of haemoglobin
      (Hb) and platelet (plt) concentrations, liver and spleen volumes were assessed.
      PATIENTS: Forty-eight patients were treated with ERT for a minimum of 6 months.
      Forty patients had Type 1 disease and eight had Type 3B. The age range was 1-70
      years (median 24 years). Duration of therapy at the time of analysis was 6-114
      months. RESULTS: Thirty-six per cent of patients started with a normal Hb
      increasing to 76% after 6 months. The mean improvement in Hb from baseline to the
      end of study period was 20 g/L, when the Hb was normal in 85% (41 patients).
      Thirty per cent of patients had a normal plt count at the start of therapy, with
      a more gradual increase in the count at 6 monthly intervals of 50, 91, 108 and
      142% of starting value. Seventy-five per cent of patients had a normal plt count
      at the end of study. Spleen volumes reduced by a mean of 56% in 33 evaluable
      patients, and the liver by 27% in 30 of 38 evaluable patients. Eight patients had
      an increase in liver volume of 28%. CONCLUSION: Enzyme replacement therapy
      produced a spectrum of beneficial responses in patients with Gaucher disease, but
      all had some evidence of reversal of haematological complications and/or
      reduction in visceromegaly. Future analyses will examine the effect of therapy on
      bone disease, prepubertal growth and quality of life.

PMID- 15737138
TI  - Selecting the future doctors: the role of graduate medical programmes.
AB  - Graduate-entry medical programmes have been introduced in many Australian states.
      This has coincided with the introduction of learner-centred, problem-orientated
      medical courses and has resulted in a need to develop new selection pathways.
      Medical schools have complemented their primary selection tool of academic
      performance with tests of personal attributes considered important in future
      doctors. Schools with graduate-entry programmes now employ a combination of the
      results of the applicant's undergraduate degree, a semistructured interview and a
      psychometric test (the Graduate Australian Medical School Admissions Test) to
      select students. Rationale for the change to graduate entry and the outcomes of
      this change will be discussed.

PMID- 15737137
TI  - Adult-onset inflammatory myopathy: North Canterbury experience 1989-2001.
AB  - AIM: To perform a clinical audit of all patients diagnosed with inflammatory
      myopathy in the North Canterbury region. METHODS: A retrospective case note audit
      of patients with a discharge diagnosis of inflammatory myopathy from June 1989 to
      June 2001 was performed. The audit was based at Christchurch Hospital, New
      Zealand, which services a population of 430,000. RESULTS: Of 77 case notes
      reviewed, 44 patients were identified who were considered to fulfil clinical
      criteria for inflammatory myopathy. There was a female preponderance (80% female,
      20% male). Diagnostic categories in descending order of frequency included:
      dermatomyositis (41%), polymyositis (39%), inclusion body myositis (IBM) (14%)
      and overlap syndromes (6%). Malignancy-associated myositis occurred in 20%
      overall (dermatomyositis 11%, polymyositis 9%). Delays in diagnosis and late age
      at presentation (average 72 years) were seen in the IBM group. Proximal limb
      weakness was common, but not universal at presentation (80%). A muscle biopsy was
      performed in all patients and electromyography in 82%. All were treated with high
      dose prednisone (0.5-1 mg/kg) of whom 29% were maintained on prednisone alone.
      Immunosuppressives/immunomodulators used included: azathioprine (58%),
      methotrexate (31%), intravenous immunoglobulin (13%), chlorambucil (13%), and
      cyclophosphamide (9%). Thirteen patients (42%) required more than one agent, with
      three trialling five agents. There were 59 relapses in 20 patients (45%), with
      mean time to first relapse of 7.8 months. At audit completion, 33% had deceased
      with malignancy and respiratory failure the main causes. CONCLUSION: Inflammatory
      myopathy is a challenging condition in both diagnosis and management. Our audit
      has shown delays in the diagnosis of IBM, a relatively high incidence of
      malignancy and a notable risk of relapse and mortality.

PMID- 15737139
TI  - Beauty is in the eye of the examiner: reaching agreement about physical signs and
      their value.
AB  - Despite advances in other areas, evidence-based medicine is yet to make
      substantial inroads on the standard medical physical examination. We have
      reviewed the evidence about the accuracy and reliability of the physical
      examination and common clinical signs. The physical examination includes many
      signs of marginal accuracy and reproducibility. These may not be appreciated by
      clinicians and could adversely affect decisions about treatment and
      investigations or the teaching and examination of students and doctors-in
      training. We provide a selected summary of the reliability and accuracy as well
      as important messages of key findings in the physical examination.

PMID- 15737140
TI  - Risk estimates for drugs suspected of being associated with Stevens-Johnson
      syndrome and toxic epidermal necrolysis: a case-control study.
AB  - The purpose of this case-control study is to estimate the risks of Stevens
      Johnson syndrome or toxic epidermal necrolysis associated with the use of
      specific drugs. The suspected cases were identified from the computerized
      hospital discharge file. We calculated crude relative risks and adjusted them for
      confounding by multivariate analysis. The analysis was based on 35 cases and 105
      controls. This study showed that the use of carbamazepine, phenytoin and
      allopurinol is most associated with the risks in the oriental population.

PMID- 15737142
TI  - Medical history from the viewpoint of the patient.
AB  - The patient narrative is now an established literary form, but has been largely
      disregarded within medicine. Medical history in general also pays only passing
      attention to the testimonies of individual patients. The patient narrative is not
      a merely contemporary development, however, but has many precursors in the past.
      This article outlines a project to bring medical history and the patient
      narrative into relationship and thereby to give the patient an intellectual
      history.

PMID- 15737141
TI  - Intestinal pseudo-obstruction complicating multiple sclerosis.
AB  - Three patients with intestinal pseudo-obstruction secondary to multiple sclerosis
      are reported. This is a serious complication with significant morbidity and
      mortality, which is infrequently recognized in clinical practice and rarely
      reported in the medical literature.

PMID- 15737143
TI  - Pleural mesothelioma with extension into the thoracic spinal cord.

PMID- 15737144
TI  - On not becoming a writer ...

PMID- 15737145
TI  - On not becoming a doctor ...

PMID- 15737146
TI  - Respiratory failure precipitated by salbutamol.

PMID- 15737147
TI  - Propionibacterium acnes sacroiliitis abscess: the private role of biopsy.

PMID- 15737148
TI  - Cyclical Cushing's disease causing recurrent oedema and knee effusions.

PMID- 15737149
TI  - Day care center characteristics and children's respiratory health.
AB  - Day care centers provide an important exposure arena with potential harmful
      health effects for children. This study has linked health effect data from a
      survey among 942 3-5-year-old Oslo children with information on day care center
      characteristics collected during inspection of the 175 day care centers these
      children attended. The aim of the study was to estimate associations between
      dampness problems and other building characteristics and several respiratory
      health outcomes. Dampness problems (sign of molds, water leakage, damage to
      floor/wall) were observed in 51% of the day care centers. In multiple logistic
      regression analyses none of the studied symptoms and diseases (nightly cough,
      blocked or runny nose without common cold, wheeze, heavy breathing or chest
      tightness, the common cold, tonsillitis/pharyngitis, otitis media, bronchitis,
      pneumonia, asthma, and allergic rhinitis) were systematically associated with
      dampness problems or type of ventilation in day care centers. None of the studied
      indicators of day care center exposures were found to have a clear effect on day
      care children's respiratory health. Even so this study does not rule out negative
      health effects of day care center exposures. The study demonstrates that
      population-based studies of these relations are demanding with regard to
      assessment of exposure and health outcomes. PRACTICAL IMPLICATIONS: Simple and
      easy-to-register indicators of exposures like dampness problems and type of
      ventilation assessed in 175 day care centers were not related to respiratory
      health among 3-5-year-old Norwegian children attending the day care centers. The
      study does not rule out negative health effects of day care center exposures, but
      demonstrates methodological challenges needed to be addressed in studies of
      health effects of the day care environment.

PMID- 15737151
TI  - Role of air distribution in SARS transmission during the largest nosocomial
      outbreak in Hong Kong.
AB  - Severe acute respiratory syndrome (SARS) is primarily transmitted by bio-aerosol
      droplets or direct personal contacts. This paper presents a detailed study of
      environmental evidence of possible airborne transmission in a hospital ward
      during the largest nosocomial SARS outbreak in Hong Kong in March 2003.
      Retrospective on-site inspections and measurements of the ventilation design and
      air distribution system were carried out on July 17, 2003. Limited on-site
      measurements of bio-aerosol dispersion were also carried out on July 22.
      Computational fluid dynamics simulations were performed to analyze the bio
      aerosol dispersion in the hospital ward. We attempted to predict the air
      distribution during the time of measurement in July 2003 and the time of exposure
      in March 2003. The predicted bio-aerosol concentration distribution in the ward
      seemed to agree fairly well with the spatial infection pattern of SARS cases.
      Possible improvement to air distribution in the hospital ward was also
      considered. PRACTICAL IMPLICATIONS: Our study revealed the need for the
      development of improved ventilation and air-conditioning systems in an isolation
      ward or a general hospital ward for infectious respiratory diseases. The outbreak
      in Ward 8A, which was in a general hospital and could house nearly 40 patients,
      demonstrated the cross-infection risks of respiratory infectious diseases in
      hospitals if a potential highly infectious patient was not identified and
      isolated. Our example simulation, which extended the SARS Busters' design for an
      isolation room to Ward 8A, demonstrated that there was room for improvement to
      minimize cross-infection in large general hospital wards.

PMID- 15737150
TI  - Indoor/outdoor relationships of carbon monoxide and oxides of nitrogen in
      domestic homes with roadside, urban and rural locations in a central Indian
      region.
AB  - Indoor air quality (IAQ) has been a matter of public concern these days whereas
      air pollution is normally monitored outdoors as part of obligations under the
      National air quality strategies. Much little is known about levels of air
      pollution indoors. Simultaneous measurements of indoor and outdoor carbon
      monoxide (CO) and oxides of nitrogen (NO and NO2) concentrations were conducted
      at three different environments, i.e. rural, urban and roadside in Agra, India,
      using YES - 205 multigas monitor during the winter season, i.e. October 2002
      February 2003. A statistical correlation analysis of indoor concentration levels
      with outdoor concentrations was carried out. CO was maximum at roadside locations
      with indoor concentrations 2072.5 +/- 372 p.p.b. and outdoor concentrations 1220
      +/- 281 p.p.b. (R2 = 0.005). Oxides of nitrogen were found maximum at urban site;
      NO concentration was 385 +/- 211 and 637 +/- 269 p.p.b. for indoors and outdoors
      respectively (R2 = 0.90792), where as NO2 concentration was 255 +/- 146 p.p.b.
      for indoors and 460 +/- 225 p.p.b. for outdoors (R2 = 0939464). Although indoor
      concentration at all the houses of the three sites have a positive correlation
      with outdoor concentration, CO variation indoors was very less due to outdoor
      sources. An activity schedule of inside and outside these homes were also
      prepared to see its influence and concentrations of pollutants. As standards for
      indoor air were not available for the Indian conditions these were compared with
      the known standards of other countries, where as outdoor concentrations were
      compared with the standards given by the Central Pollution Control board, which
      shows that indoor concentrations of both NO(x) and CO lie below permissible
      limits but outdoor concentrations of NO(x) cross the standard limits. PRACTICAL
      IMPLICATIONS: ''India currently bears the largest number of indoor air pollution
      (IAP) related health problems in world. An estimated 500,000 women & children die
      in India each year due to IAP-related cause--this is 25% of estimated IAP-related
      deaths worldwide. This study will be useful for policy makers, health related
      officials, academicians and Scientists who have interest in countries of
      developing world''.

PMID- 15737152
TI  - Multi-zone modeling of probable SARS virus transmission by airflow between flats
      in Block E, Amoy Gardens.
AB  - More than 300 residents of a private high-rise housing estate were infected with
      severe acute respiratory syndrome within a short period during the 2003 epidemic
      in Hong Kong. The outbreak occurred after the identified index patient visited a
      flat on a middle floor in Block E of the Amoy Gardens estate on two nights.
      Approximately 45% of the subsequently infected people resided in Block E, while
      the other 55% of infected cases mainly resided in six other blocks close to Block
      E. The distribution of the infected flats in Block E conformed to a non-uniform
      spatial pattern. Probable environmental causes for airborne transmission
      associated with the air movements between flats in Block E are identified. The
      well-established multi-zone airflow modeling method was used to analyze the virus
      laden bio-aerosol dispersion between flats through door and window leakage areas
      in Block E under six different scenarios. The distribution of infection risk in
      Block E matched with the virus concentrations in flats predicted with the use of
      multi-zone modeling. Our study shows the importance of ventilation design in high
      rise residential apartments. PRACTICAL IMPLICATIONS: The present study on the
      Amoy Gardens outbreak presented a scenario in which crowded living spaces might
      lead to infection disasters. There is a need to improve the current sanitary
      drainage design and maintenance standards to avoid any leakage of foul gas into
      the indoor environments. Our study revealed the need for a review of indoor air
      quality and ventilation design in buildings including offices, homes and hotels.
      The study has implications to public health in, for example, the control of other
      airborne respiratory infectious diseases such as influenza, and in bio-terror
      safety in buildings.

PMID- 15737153
TI  - Does the triad of fungi, bacteria and exposure to moisture have an impact on
      chronic hyperplastic sinusitis?
AB  - Here we evaluated a possible relationship between chronic hyperplastic sinusitis
      (CHS) and moisture exposure and secondly a seasonal variation of fungal and
      bacterial findings in the healthy nose. In 28 CHS patients sinus mucus was
      collected during endoscopic sinus surgery. Samples from the nasal cavities of 19
      healthy volunteers were collected by nasal lavage (NAL) in January and in
      September. Bacterial culture and fungal staining and culture were carried out.
      Histological samples from the sinus mucosa were obtained. Patients' medical
      history and environmental factors were enquired. Mold odor or moisture problems
      in the home or work environment were reported by 46% of the CHS patients.
      Patients who reported moisture exposure did not differ significantly from those
      who had not been exposed with regards to microbiological findings, tissue
      eosinophilia, and earlier operations. Cladosporium (16%) and Alternaria (11%)
      were found in NAL fluid collected in the autumn from the control subjects. No
      fungi were isolated from samples taken during the winter. An association between
      CHS or fungal sinusitis and moisture damage was not apparent in the present
      study. The fungal findings in the nasal cavity reflect the environmental
      exposure. This should be taken into account when NAL is used for microbiological
      studies. PRACTICAL IMPLICATIONS: Living in a moldy house or working in a similar
      environment may increase the risk of respiratory symptoms and infections.
      However, our results suggest that chronic hyperplastic sinusitis and fungal
      sinusitis are not associated with moisture exposure. The nose is a good collector
      of particles in the air. Especially samples taken by the nasal lavage method
      reflect the environmental exposure. This should be taken into account when this
      method is used for microbiological studies.

PMID- 15737154
TI  - Sick building syndrome and perceived indoor environment in relation to energy
      saving by reduced ventilation flow during heating season: a 1 year intervention
      study in dwellings.
AB  - Ventilation in Scandinavian buildings is commonly performed by means of a
      constant flow ventilation fan. By using a regulated fan, it is possible to make a
      seasonal adjustment of outdoor ventilation flow. Energy saving can be achieved by
      reducing the mechanical ventilation flow during the heating season, when natural
      ventilation driven by temperature differences between outdoor and indoor is
      relatively high. This ventilation principle has been called 'seasonally adapted
      ventilation (SAV)'. The aim was to study if a 25-30% reduction of outdoor
      ventilation flow during heating season influenced sick building syndrome (SBS)
      and the perception of the indoor environment. This was done in a 1-year cross
      over intervention study in 44 subjects in a multi-family building. During the
      first heating season (November to April), one part of the building (A) got a
      reduced flow during the heating season [0.4-0.5 air exchanges per hour (ACH)]
      while the other part (B) had constant flow (0.5-0.8 ACH). The next heating
      season, part A got constant flow, while part B got reduced ventilation flow.
      Reduced ventilation increased the relative air humidity by 1-3% in the living
      room (mean 30-37% RH), 1-5% in the bathroom (mean 48-58% RH) during heating
      season. The room temperature increased 0.1-0.3 degrees C (mean 20.7-21.6 degrees
      C), mean carbon dioxide (CO2) concentration in the bedroom increased from 920 to
      980 p.p.m. at reduced flow. The indoor air quality was perceived as poorer at
      reduced outdoor airflow, both in the bedroom and in the apartment as a whole.
      There was a significant increase of stuffy odor (P = 0.05) at reduced outdoor
      airflow and the indoor air quality was perceived as poorer, both in the bedroom
      (P = 0.03) and in the apartment as a whole (P = 0.04). No significant influence
      on SBS symptoms or specific perceptions such as odors, draught, temperature, air
      dryness or stuffy air could be detected. In conclusion, reducing the ventilation
      flow in dwellings to a level below the current Swedish ventilation standard (0.5
      ACH) may cause a perception of impaired air quality. Technical measurements could
      only demonstrate a minor increase of indoor temperature, relative air humidity,
      and bedroom CO2 concentration. This illustrates that it is important to combine
      technical measurements with a longitudinal evaluation of occupant reactions, when
      evaluating energy-saving measures. PRACTICAL IMPLICATIONS: It is important to
      combine technical measurements with a longitudinal evaluation of occupant
      reactions, when evaluating energy-saving measures. Reduction of outdoor airflow
      in dwellings below the current ventilation standard of 0.5 ACH may lead to a
      perception of impaired air quality, despite only a minor increase of bedroom CO2
      concentration.

PMID- 15737155
TI  - The effectiveness of stand alone air cleaners for shelter-in-place.
AB  - Stand-alone air cleaners may be efficient for rapid removal of indoor fine
      particles and have potential use for shelter-in-place (SIP) strategies following
      acts of bioterrorism. A screening model was employed to ascertain the potential
      significance of size-resolved particle (0.1-2 microm) removal using portable high
      efficiency particle arresting (HEPA) air cleaners in residential buildings
      following an outdoor release of particles. The number of stand-alone air
      cleaners, air exchange rate, volumetric flow rate through the heating,
      ventilating and air-conditioning (HVAC) system, and size-resolved particle
      removal efficiency in the HVAC filter were varied. The effectiveness of air
      cleaners for SIP was evaluated in terms of the outdoor and the indoor particle
      concentration with air cleaner(s) relative to the indoor concentration without
      air cleaners. Through transient and steady-state analysis of the model it was
      determined that one to three portable HEPA air cleaners can be effective for SIP
      following outdoor bioaerosol releases, with maximum reductions in particle
      concentrations as high as 90% relative to conditions in which an air cleaner is
      not employed. The relative effectiveness of HEPA air cleaners vs. other removal
      mechanisms was predicted to decrease with increasing particle size, because of
      increasing competition by particle deposition with indoor surfaces and removal to
      HVAC filters. However, the effect of particle size was relatively small for most
      scenarios considered here. PRACTICAL IMPLICATIONS: The results of a screening
      analysis suggest that stand-alone (portable) air cleaners that contain high
      efficiency particle arresting (HEPA) filters can be effective for reducing indoor
      fine particle concentrations in residential dwellings during outdoor releases of
      biological warfare agents. The relative effectiveness of stand-alone air cleaners
      for reducing occupants' exposure to particles of outdoor origin depends on
      several factors, including the type of heating, ventilating and air-conditioning
      (HVAC) filter, HVAC operation, building air exchange rate, particle size, and
      duration of elevated outdoor particle concentration. Maximum particle reductions,
      relative to no stand-alone air cleaners, of 90% are predicted when three stand
      alone air cleaners are employed.

PMID- 15737156
TI  - A study of reactive oxygen species in mainstream of cigarette.
AB  - Reactive oxygenated species (ROS) not only exist in living organisms, they also
      exist in our environment. Combustion process and photochemical reactions are the
      major source of environmental ROS, and combustion process produced ROS has been
      gradually gaining attention in recent years. The purpose of this study is to
      determine the concentrations of ROS in the mainstream smoke of cigarettes sold in
      the marketplace using the DCFH2 fluorescence method and to understand particulate
      and gaseous concentrations of ROS. This research will also discuss the
      relationship between ROS and nicotine, found in popular cigarette brands, as well
      as the effectiveness of cigarette filters to remove ROS. Results indicate that
      the ROS concentration of mainstream smoke is 18.64-54.81 nmol H2O2/l while the
      correlation coefficients of nicotine and tar to total ROS are 0.959 and 0.909,
      respectively. Gaseous ROS concentrations are 14.32-39.03 nmol H2O2/l, and make up
      71.21-85.99% of the total. It can be clearly seen therefore, that ROS exist
      mainly in the gaseous phase. Particulate ROS is dominant at PM2.5
      (ROS(TSP)/ROS(PM2.5) is 0.652-0.959). The experimental results involving the
      tobacco leaves and cigarette ash show that ROS in mainstream smoke comes from the
      combustion process and not from the tobacco leaves. There is no effective means
      of eliminating ROS from mainstream smoke, regardless of whether a cigarette
      filter contains active charcoal. PRACTICAL IMPLICATIONS: This study showed that
      cigarette combustion will produce high concentration of ROS, and this high
      concentration of ROS in mainstream cigarette smoke probably is one major factor
      contributing to a high incidence of lung cancer in smokers. Environmental tobacco
      smoke (ETS) or second-hand smoke is a major indoor air pollutant that could
      potentially harm non-smokers. We will try to determine the ROS in ETS in the
      future.

PMID- 15737157
TI  - Characterization of indoor sources of fine and ultrafine particles: a study
      conducted in a full-scale chamber.
AB  - Humans and their activities are known to generate considerable amounts of
      particulate matter indoors. Some of the activities are cooking, smoking and
      cleaning. In this study 13 different particle sources were for the first time
      examined in a 32 m3 full-scale chamber with an air change rate of 1.7 +/- 0.1/h.
      Two different instruments, a condensation particle counter (CPC) and an optical
      particle counter (OPC) were used to quantitatively determine ultrafine and fine
      particle emissions, respectively. The CPC measures particles from 0.02 microm to
      larger than 1.0 microm. The OPC was adjusted to measure particle concentrations
      in eight fractions between 0.3 and 1.0 microm. The sources were cigarette side
      stream smoke, pure wax candles, scented candles, a vacuum cleaner, an air
      freshener spray, a flat iron (with and without steam) on a cotton sheet, electric
      radiators, an electric stove, a gas stove, and frying meat. The cigarette
      burning, frying meat, air freshener spray and gas stove showed a particle size
      distribution that changed over time towards larger particles. In most of the
      experiments the maximum concentration was reached within a few minutes.
      Typically, the increase of the particle concentration immediately after
      activation of the source was more rapid than the decay of the concentration
      observed after deactivation of the source. The highest observed concentration of
      ultrafine particles was approximately 241,000 particles/cm3 and originated from
      the combustion of pure wax candles. The weakest generation of ultrafine particles
      (1.17 x 10(7) particles per second) was observed when ironing without steam on a
      cotton sheet, which resulted in a concentration of 550 particles/cm3 in the
      chamber air. The highest generation rate (1.47 x 10(10) particles per second) was
      observed in the radiator test. PRACTICAL IMPLICATIONS: Humans and their
      activities are known to generate substantial amounts of particulate matter
      indoors and potentially they can have a strong influence on short-term exposure.
      In this study a quantitative determination of the emissions of fine and ultrafine
      particles from different indoor sources was performed. The aim is a better
      understanding of the origin and fate of indoor particles. The results may be
      useful for Indoor Air Quality models.

PMID- 15737159
TI  - The intimate mediator: a carer's experience of Alzheimer's.
AB  - This research arose out of a collaboration between a service user (M) and two
      researchers. Following M's invitation to us to explore issues surrounding a
      carer's experience of Alzheimer's, we jointly agreed a research strategy in which
      we would engage in a series of interviews with M, with the aim of developing
      insight into how the intimate carer's complex journey can support and benefit
      other family caregivers faced with similar challenges. Using a broadly
      hermeneutic-phenomenological method, three essential themes emerged to describe
      the carer's journey: (i) something is wrong; (ii) the challenging shared journey:
      being the carer; (iii) coping through meaning-making: advocacy. We arrive at a
      position which considers the unique role of an intimate carer as a 'liminal'
      figure between the private world of an Alzheimer's sufferer and the public world
      of health and social care systems. The paper concludes with a consideration of
      how the unique role of the intimate carer as mediator could be more respectfully
      involved as an ongoing knowledge source for care planning and treatment
      decisions. Specific areas of consideration in this regard include mechanisms for
      such user involvement in policy making, day-to-day care delivery, and
      developments in the support of other carers. We hope to highlight the 'intimacy'
      of this position and the distinctive benefits and challenges of such intimacy in
      providing a crucial level of user knowledge and 'evidence' for ongoing treatment
      decisions. We also hope to highlight the value and power of single-case study in
      generating useful insights for practice.

PMID- 15737160
TI  - Psychiatric nurses' attitudes towards identified inpatients as measured by the
      semantic differential technique.
AB  - Nursing care can figuratively be described as a gift that is given by the nurse
      in the nurse-patient relationship where attitudes play an important role for the
      gift's appearance. Sometimes patients are unwilling to or incapable of accepting
      the gift and this can lead to situations in which nurses are not able to handle
      their situation in a professional manner. This research survey aimed to
      investigate nurses' attitudes and find a structure in nurses' attitudes towards
      their patients. Six psychiatric group dwellings and six acute psychiatric
      hospital wards participated in the study. In all, 2700 assessments of 163
      patients were sent out to 160 respondents and 2436 answers were returned. The
      semantic differential technique was used. The scale has 57 bipolar pairs of
      adjective, which estimate an unknown number of dimensions of nurses' attitudes
      towards an identified patient. The respondents' answers were analysed through
      factor analysis rotated using the Varimax method and etropy-based measures of
      association combined with structural plots were also used. Both the factor
      analysis and the entropy revealed three factors, which were interpreted as being
      of evaluative type. Factor 1 was interpreted as describing nurses' answers mainly
      as a combination of an ethical and aesthetic evaluation of the patients. Factor 2
      was interpreted as being of an empathetic type and factor 3 as nurses'
      experiences of the patients' cognitive capacity. The study indicates that the
      dominant aspect of nurses' attitudes in a psychiatric context is the
      ethical/aesthetic dimension, which is an important finding for the understanding
      of nurses' attitudes and actions towards their patients.

PMID- 15737161
TI  - Long-term stress, burnout and patient-nurse relations: qualitative interview
      study about nurses' experiences.
AB  - The purpose of this study was to obtain a deeper understanding of how nurses
      experience long lasting stress and burnout. Of central interest were
      professionalism and especially patient-nurse relations. Open interviews were
      analysed according to the Grounded Theory methodology. Participants were 10
      nurses (age 30-61) from different care institutions. They had experienced long
      lasting stress and burnout, which led to absence from work for two or more
      months. The main core emerging from the data was the powerlessness in influencing
      the valuation of the work of nurses. It reflects the process of decision-making,
      in particular in the context of reorganizations that often occur without
      considering the knowledge and experience of nurses, although decisions are
      affecting their daily work in a significant way. The patient-nurse relationship
      was experienced by the participants as an important part of care. The importance
      given by nurses to their relationship with patients was not diminished by
      tiredness, but they did not to have the power to meet patients and secure quality
      of care. The solution to this situation was to go off sick and leave the work
      place.

PMID- 15737162
TI  - Qualities clients wish for in their therapists.
AB  - In this qualitative and phenomenological study we interviewed 36 clients
      following the second session of psychotherapy. We asked the clients about which
      therapist qualities they felt were important with regard to the therapist-client
      alliance. A possible change of therapist was also discussed. Behaving in a
      confidence-inspiring and calm manner were seen as good therapist qualities that
      could promote the client-therapist alliance. It was seen as important that the
      therapist was prepared and had a plan for therapy. The clients felt it was vital
      that therapists were accepting and understanding. The clients also emphasized the
      importance of the therapist balancing attentive listening with questioning and
      commenting. Many clients needed two sessions before a good connection was
      established. A smaller group felt that they achieved a good or very good
      connection with their therapists immediately, while a minority of patients had
      not obtained a good connection with their therapists after two sessions. None of
      the clients wished to change therapist, and clients had few negative comments
      about the therapists. The findings underline the importance of the nonspecific
      and interpersonal aspects of therapists' behaviour in the alliance-building
      process.

PMID- 15737163
TI  - Empowerment in people with a mental illness: reliability and validity of the
      Swedish version of an empowerment scale.
AB  - Empowerment has become a widespread concept in various social policy contexts
      referring to different marginalized groups. Empowerment has also been focused
      within the mental health field although little empirical research exists. The aim
      of the present study was to investigate internal consistency and construct
      validity of the Swedish version of an empowerment scale developed for people with
      a mental illness, Making Decisions. Ninety-two persons were subject to an
      interview also comprising assessments of quality of life, needs for care,
      psychiatric symptoms, psychosocial functioning, aspects of the social network,
      rejection experiences and attitudes of devaluation/discrimination towards people
      with mental illness. The results showed that the overall scale and the subscales
      had a good internal consistency, except for the subscale power-powerlessness. A
      factor analysis revealed two superordinate factors, self-esteem and activism and
      community and power, with a satisfactory internal consistency. These two factors
      showed a good construct validity with expected associations to validation
      measures. Stigma was most markedly associated with self-esteem and activism, and
      a higher level of education was most strongly associated with community and
      power. In conclusion, the Swedish version Making Decisions may well be used in
      further studies of empowerment among people with a mental illness.

PMID- 15737164
TI  - Young women's lifestyle behaviours and their bone mineral density changes: a
      grounded theory analysis.
AB  - BACKGROUND: Only limited information is available on healthy young women's
      perspective of their own lifestyle behaviours. By lifestyle behaviours, e.g.
      smoking and physical activity, individuals have the possibility to influence bone
      mineral density (BMD). The aim of this study was to generate a theoretical model
      of lifestyle behaviours among young women with different BMD changes. METHODS:
      Data were collected by interviewing with 11 women, and the material was analysed
      by means of the grounded theory. FINDINGS: Two core categories were generated:
      (i) the respondents' outlook on life and (ii) their life situation. The
      respondents' outlook on life was either 'rigid' or 'relaxed'. Respondents who had
      a rigid outlook on life adjusted with others and had a decreased BMD while those
      with a relaxed outlook on life were doing things for fun and had an increased BMD
      level. Life situation also consisted of two categories: 'stagnation' and
      'development'. Respondents in a static life situation did not pursue any active
      actions while in a developing life situation, the respondents were actively
      striving towards a goal. Four dimensions which characterized the respondents'
      outlook on life in relation to their life situation emerged: subordinating and
      enduring with a decreased BMD level or compromising and discerning with an
      increased BMD level. CONCLUSION: It seems as if the outlook on life has a greater
      influence than the acted lifestyle behaviour for bone development. Further
      research is needed to generalize the findings of this study and to explore the
      importance of the outlook on life among women of all ages.

PMID- 15737165
TI  - Allergy-like conditions and health-care contacts among children with exclusion
      diets at school.
AB  - AIM: To find out whether children with exclusion diet at school had allergy-like
      conditions that could explain their food avoidance, the objective of this study
      was to describe health-care contacts and diagnostic testing among schoolchildren
      with exclusion diet and compare the magnitude of allergy-like conditions between
      those children who had vs. had not consulted health-care professionals. Telephone
      interviews were conducted with the parents of 230 schoolchildren, aged 6-18
      years, with certificates for exclusion diets at school. RESULTS: The majority of
      the schoolchildren (85%) had consulted health-care professionals for food-related
      problems, and 68% were doctor-diagnosed as having food hypersensitivity. Those
      who had consulted health-care professionals specifically for their food-related
      problems had more complex and severe problems compared with those who had not
      consulted health-care professionals. Breathing difficulties (27/196) and
      anaphylaxis (9/196) related to intake of food were reported only for those who
      had sought health-care professionals (n = 196). Regardless of whether the
      children had consulted the health-care professionals, their food-related problems
      were consistent with food hypersensitivity. Schoolchildren avoided food items
      known to be associated with food hypersensitivity such as tree nuts, fruit, egg,
      peanut, lactose and fish. Furthermore, 83% of the 230 children also had allergic
      diseases (i.e. asthma, eczema or hay fever) or were hypersensitive to other
      substances besides food, and 83% had at least one sibling or parent with
      hypersensitivity to foods or other substances. CONCLUSIONS AND IMPLICATIONS FOR
      THE SCHOOL NURSE: Schoolchildren with food certificates for exclusion diets,
      based on parents' statements, have food-related and allergy-like problems that
      may well motivate exclusion diets at school. The school nurses can rely on the
      parents' information as to what foods their children should avoid, even when
      doctor diagnoses have not been made or health-care consultations have not been
      carried out.

PMID- 15737166
TI  - Family, caring and ageing in the United Kingdom.
AB  - This paper provides a critical exploration of the assumptions and narratives
      underpinning the development of social policy initiatives targeting caring
      relationships based upon family ties. Using a narrative approach attention is
      drawn to the ways in which family identities are open to a far greater range of
      negotiation than is assumed by policy. Drawing on the United Kingdom as a case
      example, questions are posed about intergenerational relations and the nature of
      late life citizenship. The comparatively recent invention of narratives
      supporting 'informal care' and the link with neo-liberal and 'third way' notions
      of active citizenship are explored. As is the failure of policy developments to
      take into account the diversity of care giving styles and the complexity of
      caring relationships. It is argued that the uneven and locally specific ways in
      which policy develops enables the co-existence of a complex range of narratives
      about family, caring and ageing which address diverse aspects of the family life
      of older people in often contradictory ways.

PMID- 15737167
TI  - Women's experiences of childlessness 2 years after the end of in vitro
      fertilization treatment.
AB  - Approximately 15% of all couples in the reproductive age are involuntarily
      childless. Many of these couples consult medical experts for diagnosis and
      treatment but not all of them achieve the results. This paper describes a study
      of women's experiences of childlessness 2 years after the end of in vitro
      fertilization (IVF) treatment, which represents the end of infertility treatment
      in Swedish society. Giorgi's method, based on Husserl's phenomenology with the
      lifeworld theory, was used. The participants were eight women treated at the
      Clinic of Reproductive Medicine, Department of Obstetrics and Gynaecology,
      Sahlgrenska University Hospital, Goteborg, Sweden. Data were generated from
      transcriptions of taped interviews. Five constituents emerged from the analysis:
      (i) childlessness is a central issue in life, (ii) IVF is a positive and
      important part of life, (iii) contact with other people is not an important
      issue, (iv) the hope of achieving pregnancy still exists and (v) attempts to
      identify other central issues in life. The essence of all constituents is 'life
      grief' and expresses the grief of being childless, of not reproducing, and being
      unable to confirm one's relationship through parenthood. The result is important
      in professional caring and presents a challenge to all midwives, nurses,
      physicians and other staff who are involved in the care of involuntarily
      childless women.

PMID- 15737168
TI  - Validity and reliability testing of the Quality of Life Scale, Swedish version in
      women with fibromyalgia -- statistical analyses.
AB  - One consequence of constant widespread pain is a low quality of life. The purpose
      of the study was to examine whether the Quality of Life Scale, Swedish version
      (QOLS-S), regarded as a generic quality-of-life instrument, is a reliable and
      valid instrument for use in women with fibromyalgia (FM). Women with FM (n = 113)
      contributed data on the QOLS-S and other standardized instrument at three points
      in time. Internal consistency reliability estimates ranged from 0.89 to 0.92.
      Convergent construct validity was indicated by moderate agreement with a global
      life satisfaction question. Discriminant construct validity was denoted by low
      correlations with the physical functioning subscale of the SF-36. In a factor
      analysis three factors emerged: 'personal and social well-being', 'relations with
      others' and 'active participation'. A few of the items have high cross-loadings,
      and the instrument could be improved by rewording those items to more closely
      reflect one specific factor. Overall, these results provide evidence that the
      QOLS-S has acceptable validity and reliability for use in women with FM.

PMID- 15737169
TI  - Fruit and fibre (Pajala porridge) in the prevention of constipation.
AB  - BACKGROUND AND AIMS: Constipation is a common problem in geriatric wards and in
      the elderly population. Although high-fibre diets can help relieve constipation
      non-pharmacologically in many patients, traditional laxatives still remain the
      standard treatment. A fibre supplement in the form of raw bran is not always well
      tolerated. We wanted to study the effects of a daily consumption of a fruit- and
      fibre-rich porridge on stool frequency, perceived well-being and the costs for
      laxatives, when compared with traditional treatment with laxatives, in geriatric
      patients. METHODS: Twenty patients in secondary geriatric wards (hospital
      rehabilitation wards) were randomized into an intervention group (porridge group)
      and a control group (standard diet without porridge) for a 1-week run-in and 2
      week study, with registration of clinical data, e.g. medical treatment, laxative
      consumption, stool frequency and perceived well-being. RESULTS: The patients in
      the porridge group had a daily defaecation without laxatives on average 76% of
      the time (10.7/14 days) compared with 23% of the time (3.3/14 days) in the non
      porridge group (p = 0.003). The discomfort was less in the porridge group (2.5
      vs. 6.5 on a 10-degree visual analogue scale, p = 0.008) when compared with the
      control group. The cost for laxatives was 93% lower in the intervention group
      (2.5 vs. 37.5) for the 2-week study. CONCLUSIONS: A fibre-rich porridge was
      effective, well liked and tolerated and reduced the need for laxatives in
      geriatric patients. We conclude that a daily fibre-rich meal ought to be included
      in the treatment strategies of constipation in hospital wards.

PMID- 15737170
TI  - Swedish upper secondary school pupils' sense of coherence, coping resources and
      aggressiveness in relation to educational track and performance.
AB  - The health of an individual depends on how well he or she can handle various
      stressors in his or her environment. One vulnerable period occurs during the
      transition from child to adult. The overall aim of this research project was to
      determine whether differences in the ability to deal with stress are related to
      various health indicators, aggression, and school marks during primary and upper
      secondary school. Data were collected class-wise and 253 Swedish upper secondary
      school pupils participated. Three well-established questionnaires [Sense of
      Coherence (SOC), Coping Resources Inventory (CRI) and Aggression Questionnaire
      (AQ)] were used. In addition, blood pressure, teacher evaluation and school marks
      were collected. Some demographic data such as gender, age and type of study
      programme were also collected. Both SOC and Coping Resources Inventory correlated
      significantly positively with many of the primary and upper secondary marks,
      while the AQ had significantly negative correlations with the mark. Females
      obtained higher values than males in Coping Resources Inventory, but lower in SOC
      and AQ.

PMID- 15737171
TI  - Effects of clenbuterol on haemocoagulation process in calves.
AB  - The aim of this investigation was to study the effects of clenbuterol treatment
      (1 mug/kg b.w. i.m. for 10 consecutive days) on haemocoagulation process in seven
      calves. From each animal, blood samples were taken before (basal sample) and 24,
      72, 144, 216, 264, 336 and 360 h after the end of treatment and some parameters
      were evaluated: coagulation process [prothrombin (PTT) and thrombin times (PT)],
      a complete blood count and plasmatic levels of 3'5'-monophosphatocyclic-adenosine
      (c-AMP) . A comparison of the values in each time group during the whole course
      of the experiments shows a significant increase (P < 0.03, P < 0.01) in PT and
      PTT at 72, 144, 216 and 264 h. Significant increase (P < 0.01) in c-AMP plasma
      levels were observed at 144, 216 and 264 h. All these values returned to normal
      levels after 360 h.

PMID- 15737172
TI  - Evaluation of the suitability of monoclonal antibodies for flow cytometric
      intracellular cytokine detection in porcine peripheral blood lymphocytes.
AB  - Panels of monoclonal antibodies (mAbs) specific for porcine interleukin (IL)-2,
      IL-4, IL-6, IL-12, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha
      were evaluated for their applicability in flow cytometric intracellular cytokine
      detection. Peripheral blood mononuclear cells were short-time stimulated in the
      presence of brefeldin-A, ionomycin and phorbol-12-myristate-13-acetate, fixed and
      incubated with the respective mAbs as well as phycoerythrin-conjugated second
      step antibodies. Suitability of mAbs was judged by use of statistical data and by
      visual control of scattergrams, considering the capability of mAbs to
      discriminate between cytokine-positive and cytokine-negative cell populations.
      The number of suitable clones differed to a high degree between the investigated
      cytokines, but at least one mAb fitting for flow cytometric intracellular
      cytokine detection could be identified within each panel. Monoclonal Abs
      producing scattergrams with a clear demarcation between positive and negative
      cell populations were found within the anti-IL-2, IL-6 and IFN-gamma panels,
      whereas less well defined positive and negative cell populations could be
      generated by use of mAbs within the anti-IL-4 and TNF-alpha panels. Only one
      moderately fitting mAb was identified within the anti-IL-12 panel. After having
      evaluated the best fitting mAbs, these were used to obtain reference levels for
      the physiological range of porcine lymphocytic cytokine production in a second
      set of experiments. For that reason, 13 clinically healthy pigs aged between 6
      weeks and 6 months were investigated. Data presented are given as mean +/- SD of
      the percentage of positive-staining lymphocytes: IL-2, 45.5 +/- 27.6; IL-4, 34.1
      +/- 21.3; IL-6, 45.4 +/- 23.8; IL-12, 13.9 +/- 8.6; TNF-alpha, 43.4 +/- 11.3; IFN
      gamma, 65.5 +/- 14.8.

PMID- 15737173
TI  - Histopathological and immunohistochemical characteristics of two canine lipid
      rich mammary carcinomas.
AB  - Clinicopathological and immunohistochemical findings of two uncommon canine lipid
      rich mammary carcinomas are described. The predominant histological feature in
      both tumours was the presence of at least 80% of cells with intracytoplasmic
      vacuoles which stained positively with Sudan IV but not with alcian-blue periodic
      acid-schiff method. In both tumours, small groups of non-vacuolated cells were
      identified among the vacuolated cells. However, histological and
      immunohistochemical differences were also found between these tumours. Thus, one
      of them was composed of tumour cells with a large and single vacuole, which were
      arranged in lobular pattern, while the other neoplasm showed an intraductal
      growth of tumour cells with a fine vacuolated cytoplasm. Immunohistochemically,
      in the first tumour most vacuolated cells were positive for CK (cytokeratin)8-7,
      indicating a secretory epithelial immunophenotype while CK5 and CK8-7-expressing
      non-vacuolated cells were associated with luminal duct immunophenotype. However,
      in the second tumour the expression of CK14 in most of vacuolated cells and alpha
      smooth muscle actin (alpha-SMA) in non-vacuolated cells, alone or in combination
      with CK5 suggested a myoepithelial immunophenotype for both cell types. These
      results suggest heterogeneity of the cell type and growth pattern for this type
      of canine tumour as has been described in women but not in dogs.

PMID- 15737174
TI  - Effect of acute sublethal endotoxaemia on in vitro digital vascular reactivity in
      horses.
AB  - Endotoxaemia is a syndrome linked to the development of equine laminitis;
      however, the relationship between them is uncertain. The aim of this experiment
      was to evaluate the effect of an experimental acute sublethal endotoxaemia model
      on in vitro equine palmar digital vascular reactivity. Rings of arteries and
      veins of each forelimb were obtained from 11 clinically healthy horses submitted
      to two surgical procedures, 3 weeks apart. Before the second surgery, 0.25
      microg/kg of lipopolysaccharide from Escherichia coli O55:B5 in saline, was
      administered i.v. in 30 min. After 3 h, the vessels were harvested and submitted
      to in vitro vascular reactivity experiments and histopathology. The response to
      depolarizing Krebs solution (DKS, 40 mm), phenylephrine (PHE), acetylcholine
      (ACh) and sodium nitroprusside (SNP) were evaluated. All horses showed colic pain
      and watery diarrhoea, tachycardia, tachypnea, hyperthermia and leucopenia.
      Concentration-response curve (CRC) to PHE was shifted to the left in arteries
      rings from endotoxemic horses without any effect on vein rings. The CRC to ACh
      was shifted to the right with a reduction in the maximal response. The response
      to SNP and DKS was similar between groups. There was no evidence of
      histopathological effects. The increased response to PHE in digital arteries
      together with a reduction of the endothelium-dependent response to ACh in
      arteries and veins, confirm the existing reports where endotoxaemia was found to
      modify the digital vascular reactivity during the acute phase. As the digital
      endothelial function is impaired, there may be an increased potential to develop
      a digital prothrombotic state with a reduced vasodilatory capacity.

PMID- 15737175
TI  - Preliminary observations on the effect of parity on first day ultrasonic
      detection of embryo and its organs in bovine.
AB  - The aim of this study was to determine the effect of parity on the first day of
      ultrasonic detection of embryo and its organs using 8 MHz frequency. For this
      purpose, six nulliparous heifers, five primiparous cows and six multiparous cows
      of the Holstein breed were selected and mated by a single bull from the herd.
      From day 16 after mating, cows and heifers were examined by ultrasonography
      thrice weekly for the day of first detection of the embryo and its organs. The
      mean of first-day detection in heifers, primiparous and multiparous cows was as
      follows, respectively: allantois on days 22.3, 23 and 25.8; embryo proper on days
      21.8, 23 and 27; heartbeat of embryo on days 26.1, 26.6 and 31.1; amnion on days
      31, 31 and 30.8; limb buds on days 29.5, 28.8 and 30.6; stomach (abomasum) on
      days 32.2, 38.6 and 36.8; spinal column on days 32.6, 33.4 and 37.3; placentomes
      on days 33.3, 37 and 35.3; eyes on days 35.1, 35.4 and 38.6 and lens on days 40,
      41.4 and 44. Although the mean of first day observation of all structures in
      heifers tends to be earlier than in the other groups, statistically, allantois,
      the embryo proper and its heartbeat in heifers and primipara were visualized
      significantly earlier than in multiparous cows. However, there were no
      differences between heifers and primiparous cows.

PMID- 15737176
TI  - Effects of three anthelmintic regimes on milk yield of ewes and growth of lambs.
AB  - Forty ewes were allocated into one of four groups (n = 10) and were treated with
      albendazole (ALB) (3.8 mg kg(-1)) before lambing (group A), with ALB before and
      after lambing (group B), with moxidectin (MXD) (0.2 mg kg(-1)) before lambing
      (group C) or were untreated controls (group D). Counts of nematode eggs in faeces
      and coprocultures were carried out during the study, as well as ewes' milk yield
      measurements and lamb weighings. Pre-treatment mean eggs per gram (epg) counts
      were 640, 715, 625 and 630 for groups A, B, C and D, respectively (P > 0.05);
      respective counts 21 days after treatment were 5, 0, 0 and 690 epg, whilst 70
      days after treatment they were 380, 145, 40 and 1120 epg. Mean lactation milk
      yield was 3527.5, 3893.5, 3786.4 and 3285.9 ml for groups A, B, C and D,
      respectively; no significant difference was evident among the four groups in milk
      yield collected during the suckling period, although subsequently, group B or C
      ewes yielded significantly more milk than controls (P < 0.05). Mean birthweight
      of lambs were 3.56, 3.45, 3.59 and 3.26 kg for groups A, B, C and D, respectively
      (P = 0.045); subsequently, lambs from treated ewes were significantly heavier
      than lambs from control animals (P < 0.001). We conclude that anti-parasitic
      treatment during the last month of pregnancy contributed to an increased
      birthweight of lambs of treated ewes, whilst the cumulative effect of two doses
      of ALB or the long persistent efficacy of MXD provided a longer protection of
      animals against new parasitic infections and contributed to a lactation
      persistence.

PMID- 15737177
TI  - Longitudinal left ventricular myocardial dysfunction assessed by 2D colour tissue
      Doppler imaging in a dog with systemic hypertension and severe arteriosclerosis.
AB  - A 12-year-old sexually intact male Vendee Griffon Basset was presented for acute
      pulmonary oedema. Severe systemic systolic arterial hypertension (SAH) was
      diagnosed (290 mmHg). Despite blood and abdominal ultrasound tests, the
      underlying cause of the systemic hypertension could not be determined, and
      primary SAH was therefore suspected. Conventional echocardiography showed
      eccentric left ventricular hypertrophy with normal fractional shortening. Despite
      this apparent normal systolic function, 2D colour tissue Doppler imaging (TDI)
      identified a marked longitudinal systolic left ventricular myocardial alteration,
      whereas radial function was still preserved. Three months later, the dog
      underwent euthanasia because of an acute episode of distal aortic
      thromboembolism. Necropsy revealed severe aortic and iliac arteriosclerosis. SAH
      related to arteriosclerosis is a common finding in humans, but has not been
      previously described in dogs. Moreover, its consequence on longitudinal
      myocardial function using TDI has never been documented before in this species.

PMID- 15737178
TI  - Morbillivirus infections in aquatic mammals: a brief overview.
AB  - Since 1987, at least eight morbillivirus infection (MI) epidemics have caused
      mass mortality of several free-living pinniped and cetacean populations around
      the world. The responsible agents, all belonging to the genus Morbillivirus
      (family Paramyxoviridae), have been characterized as either "canine distemper
      virus" strains, infecting pinnipeds, or as three new morbilliviruses, namely
      "phocid (phocine) distemper virus" , "porpoise morbillivirus" and "dolphin
      morbillivirus" . The last two agents are currently gathered under the common
      denomination of "cetacean morbillivirus". At post-mortem examination, a commonly
      occurring macroscopic lesion is represented by more or less severe bilateral
      pneumonia, with consolidation, congestion and oedema of both lungs, which fail to
      collapse. Histologically, a non-suppurative broncho-interstitial pneumonia,
      characterized by type II pneumocyte hyperplasia and by formation of
      endobronchial, endobronchiolar and endoalveolar "Warthin-Finkeldey type"
      syncytia, as well as a multifocal, non-suppurative encephalitis, associated with
      a severe and generalized lymphoid tissue depletion, are common pathological
      findings. Furthermore, eosinophilic viral inclusions are often detected, at both
      the intracytoplasmic and intranuclear level, within bronchial and bronchiolar
      epithelial, pulmonary syncytial, neuronal and other cell types. These inclusions,
      along with lymphoid and other cellular elements, are often found to be
      immunohistochemically positive for morbillivirus antigen. Among the still
      debated, or even controversial issues regarding MI in sea mammals, the one
      related to the origin of their causative agents is of particular concern. Another
      intriguing issue regards the synergistic effects, if any, associated with chronic
      exposure to a number of environmental pollutants, such as organochlorines and
      heavy metals. In fact, it is also unknown whether and how these chemicals
      contribute towards modulating the pathogenic and pathogenetic activity primarily
      displayed by sea mammal morbilliviruses.

PMID- 15737179
TI  - In vivo culture of IVM/IVF embryos in bovine oviducts by transvaginal endoscopy.
AB  - This study was conducted to establish a new approach for in vivo culture of in
      vitro produced embryos in the bovine oviduct by transvaginal endoscopy. Embryos
      were in vitro matured, fertilized and cultured for 1-4 days and assigned to
      groups consisting of 10-30 embryos. Embryos were transferred unilaterally into
      oviducts of 24 heifers by the means of transvaginal endoscopy. After 3-6 days of
      in vivo incubation embryos were re-collected. Experiment I aimed to evaluate the
      capability of embryos to migrate to the uterus. The uterine horns of four animals
      were flushed first, followed by a combined flushing of both oviducts and uterine
      horns resulting in collection rates of 31 and 34%, respectively. In experiment
      II, the transfer of embryos into the oviduct close to ovulation (day 1-2-
      experiment IIA) or at a more advanced cyclic stage (day 3--experiment IIB)
      succeeded in the collection of 46 and 34% of the transferred complexes, of which
      13 and 37% showed the blastocyst stage. This is the first report of successful
      recovery of transferable blastocysts by transvaginal endoscopy after tubal in
      vivo culture in the homologous species of originally in vitro produced embryos.

PMID- 15737180
TI  - Muscle metabolic changes associated with long-term inhalation anaesthesia in the
      horse analysed by muscle biopsy and microdialysis techniques.
AB  - During anaesthesia in the horse, muscle blood flow has been found to be reduced,
      possibly leading to hypoxia or ischaemia in the muscle. The aim of this study was
      to use the muscle biopsy and microdialysis techniques to determine whether long
      term inhalation anaesthesia in laterally recumbent horses induces metabolic
      changes in gluteal muscle indicative of anaerobic metabolism. Muscle biopsies and
      plasma samples were taken from seven horses at the start and end of halothane
      anaesthesia. In six isoflurane-anaesthetised horses, given three pharmacological
      provocations (dobutamine, detomidine, acepromazine), repeated blood samples and
      microdialysis was performed during anaesthesia and muscle biopsies were taken
      before and at the end of anaesthesia. Adenosine triphosphate (ATP), adenosine
      diphosphate, adenosine monophosphate, inosine monophosphate (IMP) creatine
      phosphate and lactate concentrations did not differ between dependent and non
      dependent muscles at either sampling time. Creatine phosphate decreased in both
      the halothane (-38%) and isoflurane (-28%) group. In the halothane group, ATP was
      decreased (-15%) at the end of anaesthesia, while IMP was increased (+32%).
      Lactate in muscle and plasma increased in both groups. Lactate in dialysate
      increased after induction and remained elevated above plasma concentrations.
      These results show that long-term inhalation anaesthesia in horses is associated
      with an anaerobic metabolic response within the muscle and that microdialysis can
      be used to detect metabolic changes within the muscle during equine anaesthesia.

PMID- 15737183
TI  - Toward reduction of misclassification in the biology of melanoma.

PMID- 15737184
TI  - The human type II keratin gene cluster on chromosome 12q13.13: final count or
      hidden secrets?

PMID- 15737185
TI  - A scientific look at seasonality of symptom severity in atopic dermatitis.

PMID- 15737186
TI  - Why is the mortality of bullous pemphigoid greater in Europe than in the US?

PMID- 15737187
TI  - Transglutaminase function in epidermis.
AB  - Surface epithelial cells, such as the epidermal keratinocyte, undergo a process
      of terminal cell differentiation that results in the construction of a
      multilayered epithelium. This epithelium functions to protect the organism from
      the environment. Transglutaminases, enzymes that catalyze the formation of
      isopeptide protein-protein cross-links, are key enzymes involved in the
      construction of this structure. This brief review will focus on the role of these
      enzymes in constructing the epidermal surface.

PMID- 15737188
TI  - Diagnostic applicability of in vivo confocal laser scanning microscopy in
      melanocytic skin tumors.
AB  - In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool
      that allows the examination of skin morphology in real time at a resolution equal
      to that of conventional microscopes. The aim of the study was to test the
      applicability of CLSM to the diagnostic discrimination of benign nevi and
      melanoma. five independent observers without previous experience in CLSM received
      a standardized instruction about diagnostic CLSM features. Subsequently, 117
      melanocytic skin tumors (90 benign nevi and 27 melanoma), imaged using a
      commercially available, near-infrared, reflectance confocal laser scanning
      microscope, were evaluated by each observer. Overall, sensitivity of 88.15% and
      specificity of 97.60% was achieved by the five observers. Logistic regression
      analysis revealed that mainly cytomorphology, architecture and keratinocyte cell
      borders should be taken into account for diagnostic decisions. Remarkably, using
      the presence or absence of monomorphic melanocytes as a single diagnostic
      criterion, the classification results with a sensitivity of 98.15% and a
      specificity of 98.89% were superior to the intuitive, integrative judgement of
      the observers. This first sensitivity and specificity study with CLSM has yielded
      promising results. CLSM provides new and useful information to the clinician
      diagnosing melanocytic skin tumors.

PMID- 15737189
TI  - Psoriasis phenotype at disease onset: clinical characterization of 400 adult
      cases.
AB  - Psoriasis is clinically a heterogeneous disease. Detailed evaluation of phenotype
      at disease onset is lacking. This study is a baseline characterization of 400
      adult individuals with first time incidence of psoriasis on non-hairy skin,
      describing clinical phenotypes and putative environmental triggers at disease
      onset. In total, 74 patients with guttate and 326 patients with non-guttate
      phenotype, the majority with plaque psoriasis, were included. Guttate phenotype
      was associated with younger age and recent infection in 84%, where acute
      streptococcal pharyngitis was verified in 63%. The predominating factor
      associated with onset of plaque psoriasis was a recent life crisis (46%). A
      positive family history for psoriasis was approximately the same in both groups.
      Psoriasis arthropathy was diagnosed in 5% of guttate and 15% of non-guttate
      patients, with enthesopathy being the dominant symptom among guttate patients.
      This study confirms the strong link between onset of guttate psoriasis phenotype
      and streptococcal throat infection, whereas onset of plaque psoriasis was highly
      associated with a preceding distinct stressful life event. Longitudinal follow-up
      of the patients will provide robust information about disease development and
      response to treatment.

PMID- 15737190
TI  - High levels of ultraviolet B exposure increase the risk of non-melanoma skin
      cancer in psoralen and ultraviolet A-treated patients.
AB  - Sunlight and psoralen and ultraviolet A (PUVA) are risk factors for the
      development of squamous cell carcinoma (SCC) and, to a lesser extent, basal cell
      carcinoma (BCC). Ultraviolet B (UVB) therapy, used for the treatment of
      psoriasis, might also increase the risk of these tumors. We studied the relation
      of skin cancer incidence to UVB use among 1380 adult subjects enrolled in a long
      term safety trial of PUVA therapy. We used negative binomial regression models to
      quantify the association between UVB and the development of non-melanoma skin
      cancer (NMSC), controlling for known confounders. High UVB exposure (> or =300
      treatments vs <300 treatments) was associated with a modest but significant
      increase in SCC (adjusted incidence rate ratio (IRR)=1.37, 95% confidence
      interval (CI)=1.03-1.83) and BCC (adjusted IRR=1.45, 95% CI=1.07-1.96) risk.
      Among patients with <100 PUVA treatments, high UVB exposure was significantly
      associated with the development of SCC (adjusted IRR=2.75, 95% CI=1.11-6.84) and
      BCC (adjusted IRR=3.00, 95% CI=1.30-6.91) on body sites typically exposed to UVB
      therapy but not on chronically sun-exposed sites typically covered during
      therapy. For adults with high UVB exposure levels, UVB confers a modest increase
      in NMSC risk, much less than that observed with PUVA. Therefore, UVB remains a
      relatively low-risk treatment for psoriasis.

PMID- 15737191
TI  - Seasonality in symptom severity influenced by temperature or grass pollen:
      results of a panel study in children with eczema.
AB  - Although seasonal variations are well known in many patients with eczema, no
      systematic population-based panel study evaluating seasonality and quantifying
      the influence of factors like climate and pollen on symptom variations has been
      conducted so far. Thirty-nine children with eczema, who had been identified in
      1996 in a cross-sectional study on 1673 6-y-olds in Augsburg (Germany),
      participated in the study. Between March and September 1999, they daily recorded
      itch, extent, and possibly triggering factors on quantitative scales. Daily
      temperature, humidity, radiation, and pollen concentration were measured. Mixed
      linear models, taking the time series structure and confounding into account,
      were used for analysis. Seasonal patterns were significantly different between
      children: twenty-one had symptoms mainly in winter. They were affected by changes
      in outdoor temperature: itch was reduced by 22% (95% confidence interval (CI):
      16%-27%) and extent by 65% (CI: 54%-72%) per 15 degrees C temperature increase.
      Eighteen children exhibited more symptoms in summer and especially during days
      with high grass-pollen exposure when itch was 16% higher (CI: 8%-24%) and extent
      19% (CI: 2%-39%). This effect was stronger for children sensitized against
      pollen. Consideration of the individual type of eczema may help to arrange
      appropriate preventive and therapeutic measures.

PMID- 15737192
TI  - PADMA 28: a multi-component herbal preparation with retinoid-like dermal activity
      but without epidermal effects.
AB  - PADMA 28, a multi-component herbal mixture formulated according to an ancient
      Tibetan recipe, was assessed for effects on human dermal fibroblasts and
      epidermal keratinocytes in monolayer culture, and for effects on human skin in
      organ culture. PADMA 28 stimulated survival of fibroblasts in monolayer culture.
      In fibroblast monolayer culture and human skin organ culture, levels of matrix
      metalloproteinase-1 (MMP-1; interstitial collagenase) were reduced and type I
      procollagen production was increased. When keratinocytes were examined, there was
      no evidence of growth stimulation over a wide range of PADMA 28 concentrations.
      At high concentration, PADMA 28 inhibited keratinocyte proliferation. When organ
      cultures of human skin were treated with PADMA 28, there was no evidence of
      hyperplastic growth in the epidermis. Topical treatment of rhino mice with PADMA
      28 failed to induce epidermal hyperplasia and was completely non-irritating. The
      ability to stimulate collagen production and inhibit the major collagen-degrading
      enzyme in skin without inducing a hyperplastic response in the epidermis may
      provide a basis for development of the herbal preparation as a "skin-repair"
      agent.

PMID- 15737193
TI  - Inherited junctional epidermolysis bullosa in the German Pointer: establishment
      of a large animal model.
AB  - Junctional epidermolysis bullosa (JEB) is a genodermatosis suitable for gene
      therapy because conventional treatments are ineffective. Here, we elucidate the
      genetic basis of mild JEB in a breed of dogs that display all the clinical traits
      observed in JEB patients. The condition is associated with reduced expression of
      laminin 5 caused by a homozygous insertion (4818+207ins6.5 kb) of repetitive
      satellite DNA within intron 35 of the gene (lama3) for the laminin alpha3 chain.
      The intronic mutation interferes with maturation of the alpha3 pre-messenger RNA
      resulting in the coexpression of a transcript with a 227 nucleotide insertion and
      a wild-type mRNA that encodes scant amounts of the alpha3 polypeptide. Our
      results show that the amino acid sequence and structure of the canine and human
      alpha3 chain are highly conserved and that the reduced expression of laminin 5
      affects the adhesion and clonogenic potential of the JEB keratinocytes. These JEB
      dogs provide the opportunity to perform gene delivery in a naturally occurring
      genodermatosis and to evaluate host tolerance to recombinant laminin 5.

PMID- 15737194
TI  - Characterization of new members of the human type II keratin gene family and a
      general evaluation of the keratin gene domain on chromosome 12q13.13.
AB  - The recent completion of a reference sequence of the human genome now allows a
      complete characterization of the type II keratin gene domain on chromosome
      12q13.13. This, domain, approximately 780 kb in size, is present on nine
      bacterial artificial chromosome clones sequenced by the Human Genome Sequencing
      Project. The type II keratin domain contains 27 keratin genes and eight
      pseudogenes. Twenty-three of these genes and four pseudogenes have been
      previously reported. This study describes, in addition to the genomic sequencing
      of the K2p gene and the bioinformatic identification of four keratin pseudogenes,
      the characterization of cDNA corresponding to three previously undescribed
      keratin genes K1b, K6l, and Kb20, as well as cDNA sequences for the previously
      described keratin genes hHb2, hHb4, and K3. Northern analysis of the new keratins
      K1b, K6l, K5b, and Kb20 using mRNA of major organs as well as of specific
      epithelial subtypes shows singular expression of these keratins in skin, hair
      follicles and, for K5b and Kb20, in tongue, respectively. In addition, the
      obvious discrepancies between the current reference sequence of the human genome
      and the previously described gene/cDNA sequences for K6c, K6d, K6e, K6f, K6h are
      investigated, leading to the conclusion that K6c, K6d as well as K6e, K6f are
      probably polymorphic variants of K6a and K6h, respectively. All 26 human type II
      keratins found on this domain as well as K18, dtype 1 Keratin, are identified at
      the genomic and transcriptional level. This appears to be the total complement of
      functional type II keratins in humans.

PMID- 15737195
TI  - Single-point haplotype scores telomeric to human leukocyte antigen-C give a high
      susceptibility major histocompatibility complex haplotype for psoriasis in a
      Caucasian population.
AB  - Psoriasis is a chronic inflammatory skin disease that affects 0.1%-5% depending
      on the population. PSORS1 is the major susceptibility locus, accounting for
      approximately 33%-50% of the genetic component of psoriasis among Caucasians.
      PSORS1 is located within the major histocompatibility complex (MHC) locus on
      6p21.3. Its position has been refined to hundreds of kilobase and the region
      located at approximately 100-200 kb telomeric to human leukocyte antigen (HLA)-C
      is a very strong candidate. To determine the MHC psoriasis risk haplotype, we
      screened the whole 46 kb interval for single-nucleotide polymorphisms (SNP) and
      identified 138 SNP. We genotyped 29 SNP throughout this region in psoriatic
      nuclear families. We calculated the frequency of haplotypes generated by the 29
      SNP using all genotyped founder individuals and found four common haplotype with
      frequency >0.10. We then used SNPtagger to derive the best six SNP and fed these
      into Transmit using 148 nuclear families. We found that CTGGAC haplotype is a
      single-point score haplotypes telomeric to HLA-C and gives a 1 df, chi2 of 50.27
      (p<0.0001). Most importantly the six selected SNP accurately tagged the most
      common haplotype found in this region. Moreover, using the same program
      (Transmit) we show that the association with CTGGAC is higher than the one with
      HLA-Cw6 (chi2=10.53; p=0.0051). Our results give scores as high as the highest
      single-point scores suggesting that it is unlikely to be able to discriminate the
      origin of the association on this analysis on strength of association.

PMID- 15737196
TI  - Inhibition of cell proliferation by bacterial lipopolysaccharides in TLR4
      positive epithelial cells: independence of nitric oxide and cytokine release.
AB  - Phylogenetically conserved toll-like receptors (TLR) recognize "pathogen
      associated molecular patterns". Upon binding of ligands, TLR initiate innate
      immune response in immune and most likely epithelial cells. The TLR4 isoform is
      considered as a lipopolysaccharide (LPS) receptor. As shown here, a rat-tongue
      derived epithelial cell line RTE2 expressed TLR4 mRNA and functional protein. LPS
      treated RTE2 cells responded with the transient expression of inducible nitric
      oxide synthase (iNOS), an effector protein of TLR4 involved in the innate immune
      defense of monocytes. iNOS induction occurred along a nuclear factor-kappaB (NF
      kappab)-dependent pathway and correlated with the increased production of NO.
      Moreover, LPS and lipid A were potent inhibitors of proliferation of RTE2 cells,
      of mouse keratinocytes, and mouse epidermis in vivo. The inhibition depended on
      lipid A structure, i.e., it was related to the endotoxin activity of LPS and at
      least in vitro was in part mediated by NF-kappaB. C57Bl/10 ScCr mice, lacking a
      functional TLR4, did not respond with growth inhibition, strongly suggesting a
      TLR4-mediated effect. RTE2 proliferation was also inhibited by transforming
      growth factor beta (TGFbeta) and tumor necrosis factor alpha (TNFalpha), whereas
      interferon gamma (IFNgamma) was a weak inhibitor. But the growth-inhibitory
      effect of LPS on RTE2 cells was not mediated by TNFalpha, TGFbeta, or NO. It is
      concluded that besides induction of innate immune responses, LPS specifically
      induces growth arrest in epithelial tongue cells and keratinocytes in vitro and
      in mouse epidermis in a TLR4-dependent but cytokine- and NO-independent manner.

PMID- 15737197
TI  - Deficient contact hypersensitivity reaction in CD4-/- mice is because of impaired
      hapten-specific CD8+ T cell functions.
AB  - Mice deficient in the CD4 molecule (CD4-/-) are widely used to evaluate the
      requirement for CD4+ T cell help in viral, tumoral, and transplantation immunity.
      Previous studies, showing that CD4-/- mice develop impaired contact
      hypersensitivity (CHS) responses, have suggested that CD4+ T cells are required
      for the optimal induction of this skin inflammatory reaction. other studies have,
      however, demonstrated that CHS was mediated by CD8+ T cells, without the need for
      CD4+ T cell help. Here, we show that CD4-/- mice develop a normal delayed-type
      hypersensitivity response to protein antigen, which is mediated by major
      histocompatibility molecules class II-restricted CD4-CD8- T cells, but a
      decreased CHS response to 2,4-dinitro-fluorobenezene. Analysis of the hapten
      specific T cell pool demonstrates that priming of CD8+ T cells occurred normally
      in CD4-/- mice, as assessed by specific proliferative responses and interferon
      gamma (IFN-gamma) production of purified CD8+ T cells. Furthermore, CD8+ T cells
      were able to adoptively transfer a normal CHS reaction. In contrast, total lymph
      node cells from CD4-/- mice showed decreased IFN-gamma production and diminished
      specific cytotoxic T lymphocytes (CTL) activity, which could be reversed by in
      vitro restimulation with hapten-pulsed class II-deficient antigen-presenting
      cells. These data confirm that class I-restricted CD8+ T cells can fully develop
      in effectors of CHS in the absence of CD4+ T cell help and suggest that the
      impaired CHS in CD4-/- mice is because of the presence of a class II-restricted T
      cell subset, which controls CHS by inhibiting hapten-specific CTL responses.

PMID- 15737198
TI  - B cells activated in lymph nodes in response to ultraviolet irradiation or by
      interleukin-10 inhibit dendritic cell induction of immunity.
AB  - Ultraviolet (UV) radiation suppresses systemic immunity. We explored these
      cellular mechanisms by exposing mice to systemically immunosuppressive doses of
      UV radiation and then analyzing cell phenotype and function in the lymphoid
      organs. Although UV radiation increased total cell number in the draining lymph
      nodes (DLN), it did not alter the activation state of dendritic cells (DC).
      Rather, UV radiation selectively activated lymph node B cells, with these cells
      being larger and expressing higher levels of both anti-major histocompatibility
      complex II and B220 but not co-stimulatory molecules. This phenotype resembled
      that of a B cell geared toward immune tolerance. To test whether UV radiation
      activated B cells were responsible for immunosuppression, DC and B cells were
      conjugated to antigen ex vivo and transferred into naive hosts. Although DC by
      themselves activated T cells, when the B cells from UV radiation-irradiated mice
      were co-injected with DC, they suppressed DC activation of immunity. Interleukin
      (IL)-10-activated B cells also suppressed DC induction of immunity, suggesting
      that IL-10 may be involved in this suppressive effect of UV radiation. These
      results demonstrate a new mechanism of UV radiation immunosuppression whereby UV
      radiation activates B cells in the skin-DLN that can suppress DC activation of T
      cell-mediated immunity.

PMID- 15737199
TI  - Redox imbalance induced by contact sensitizers triggers the maturation of
      dendritic cells.
AB  - Although p38 mitogen-activated protein kinases (MAPK) play a crucial role in the
      activation of monocyte-derived dendritic cells (MoDC) by contact sensitizers, the
      upstream signals of p38 MAPK remain undetermined. To examine whether sensitizers
      induce redox or oxidative stress in dendritic cells (DC), which subsequently
      stimulate p38 MAPK, we measured the ratio of the oxidized (GSSG) versus reduced
      (GSH) form of cellular glutathione in MoDC stimulated with five sensitizers
      including NiCl2 and 2,4-dinitrochlorobenzene (DNCB) and three non-sensitizers
      including sodium dodecyl sulfate using colorimetric assays. All the sensitizers,
      but none of the non-sensitizers at sublethal concentration, reduced the GSH/GSSG
      ratio, which was accompanied by phosphorylation of p38 MAPK. Treatment with the
      antioxidant, N-acetyl-L-cysteine, which suppressed the reduction of the GSH/GSSG
      ratio, abrogated both the phosphorylation of p38 MAPK and the augmentation of
      CD86 expression. A similar response pattern was observed in THP-1 macrophage
      monocyte cells. Unexpectedly, however, formaldehyde (HCHO) reduced the GSH/GSSG
      ratio in MoDC, but not in THP-1. This finding, in conjunction with the
      observation that DNCB and NiCl2 reduced the GSH/GSSG ratio at different kinetics,
      indicated that the sensitizers reduced the GSH/GSSG ratio by a different
      mechanism. These data suggest that the GSH/GSSG imbalance plays a crucial role in
      triggering DC maturation by sensitizers.

PMID- 15737200
TI  - Mechanisms by which psychologic stress alters cutaneous permeability barrier
      homeostasis and stratum corneum integrity.
AB  - Although many skin disorders, including psoriasis and atopic dermatitis, are
      adversely affected by psychologic stress (PS), the pathophysiologic link between
      PS and disease expression remains unclear. Recent studies demonstrated PS-induced
      alterations in permeability barrier homeostasis, mediated by increased endogenous
      glucocorticoids. Here, we assessed the mechanisms by which PS alters stratum
      corneum (SC) function. Insomniac psychologic stress (IPS) altered both barrier
      homeostasis and SC integrity. IPS decreased epidermal cell proliferation,
      impaired epidermal differentiation, and decreased the density and size of
      corneodesmosomes (CD), which was linked to degradation of CD proteins (e.g.,
      desmoglein1). Barrier compromise was linked to decreased production and secretion
      of lamellar bodies (LB), which in turn could be attributed to a decrease in de
      novo synthesis of epidermal lipids. Topical physiologic lipids (equimolar
      cholesterol, ceramides, and free fatty acids) normalized both barrier homeostasis
      and SC integrity in IPS mice, further evidence that lipid deficiency accounted
      for these functional abnormalities. Thus, PS inhibition of epidermal lipid
      synthesis results in decreased LB formation and secretion, as well as decreased
      CD, compromising both permeability barrier homeostasis and SC integrity. These
      studies suggest that topical treatment with epidermal physiologic lipids could be
      beneficial in stress-induced, barrier-associated dermatoses, such as psoriasis
      and atopic dermatitis.

PMID- 15737201
TI  - Disturbed keratinocyte differentiation in transgenic mice and organotypic
      keratinocyte cultures as a result of spermidine/spermine N-acetyltransferase
      overexpression.
AB  - Overexpression of the rate-limiting enzyme in polyamine catabolism
      spermidine/spermine N1-acetyltransferase (SSAT) in transgenic (Tg) mouse leads to
      accumulation of putrescine in the skin and permanent hair loss at the age of 3
      wk. The hair follicles of these mice are replaced by dermal cysts and epidermal
      utriculi. Increased putrescine production is also seen in hyperproliferative
      cutaneous disorders such as in psoriasis. These disorders are characterized by
      delayed onset of epidermal differentiation characterized as reduced expression of
      terminal differentiation markers such as cytokeratins 1/10, and filaggrin and
      persisting expression of basal cell cytokeratins 5/14 in the suprabasal layers.
      The use of these markers in immunohistological analysis of SSAT Tg skin clearly
      showed signs of disturbed differentiation. To exclude the possibility that
      changes in differentiation originated from underlying connective tissue, we
      introduced SSAT gene into an established rat epidermal cell line. Organotypic
      cultures derived from the transfected cells displayed similar changes in their
      differentiation pattern as keratinocytes in Tg skin. The role of accumulated
      putrescine in cutaneous changes of SSAT Tg mice was verified by an experiment in
      which putrescine level was reduced by systemic putrescine biosynthesis
      inhibition. The putrescine reduction was sufficient to alleviate the cutaneous
      changes to such an extent that distinct hair regrowth could be seen. These
      results suggest that the cutaneous changes of SSAT Tg animals are due to
      disorders of the keratinocyte differentiation. Moreover, they strengthen the view
      that the proper regulation of polyamine metabolism plays an important role in the
      keratinocyte maturation.

PMID- 15737202
TI  - Suprabasal induction of ornithine decarboxylase in adult mouse skin is sufficient
      to activate keratinocytes.
AB  - To study the effects of de novo induction of ornithine decarboxylase (ODC)
      activity in adult, quiescent skin, we generated transgenic mice in which the
      suprabasal expression of an inducible form of the ODC protein fused to a modified
      estrogen receptor ligand-binding domain (ODCER) is driven by an involucrin
      promoter. After topical treatment with the inducing agent 4-hydroxytamoxifen
      (4OHT), ODC activity and putrescine levels were dramatically increased in the
      epidermis but not in the dermis of transgenic mice. 4OHT treatment stimulated
      both proliferation as measured by bromodeoxyuridine incorporation in basal
      epidermal cells and differentiation shown by increased expression of
      differentiation markers. Furthermore, induction of ODC activity did not rescue
      primary epidermal keratinocyte cultures isolated from ODCER2 mice from a calcium
      triggered DNA synthesis block, as measured by [3H]thymidine incorporation. In
      vivo induction of epidermal ODC enzyme activity significantly stimulated the
      vascularization of ODCER transgenic skin. Increased expression of interleukin
      1beta and keratin 6, markers of keratinocyte activation seen in wound healing,
      was also observed in 4OHT-treated transgenic skin. These results suggest that de
      novo suprabasal induction of ODC activity in adult mouse skin activates
      keratinocytes and stimulates vascularization in the dermal layer in a manner
      similar to skin undergoing wound healing.

PMID- 15737203
TI  - Mutations in gasdermin 3 cause aberrant differentiation of the hair follicle and
      sebaceous gland.
AB  - Defolliculated (Dfl) is a spontaneous mouse mutant with a hair-loss phenotype
      that includes altered sebaceous gland differentiation, short hair shafts,
      aberrant catagen stage of the hair cycle, and eventual loss of the hair follicle.
      Recently a similar mutant, finnegan (Fgn), with an identical phenotype was
      discovered during a phenotypic screen for mutations induced by chemical
      mutagenesis. The gene underlying the phenotype of both finnegan and
      defolliculated has been mapped to chromosome 11 and here we show that both mice
      harbor mutations in gasdermin 3 (Gsdm3), a gene of unknown function. Gsdm3(Dfl)
      is a B2 insertion near the 3' splice site of exon 7 and Gsdm3(Fgn) is a point
      mutation T278P. To investigate the role of the gasdermin gene family an antiserum
      was raised to a peptide highly homologous to all three mouse gasdermins and human
      gasdermin. Immunohistochemical analysis revealed that gasdermins are expressed
      specifically in cells at advanced stages of differentiation in the upper
      epidermis, the differentiating inner root sheath and hair shaft and in the most
      mature sebocytes of the sebaceous gland and preputial, meibomium, ceruminous
      gland, and anal glands. This expression pattern suggests a role for gasdermins in
      differentiation of the epidermis and its appendages.

PMID- 15737204
TI  - Feasibility of tracking phospholipid permeation into skin using infrared and
      Raman microscopic imaging.
AB  - The feasibility of monitoring the permeation of chain perdeuterated 1,2
      dipalmitoylphosphatidylcholine (DPPC-d62) and 1-palmitoyl-d31, 2
      oleoylphosphatidylcholine (P-d31OPC) vesicles into pigskin using infrared (IR)
      microscopic imaging and confocal Raman microscopy was demonstrated. The former
      technique permits the examination of the relative concentration of molecular
      species (e.g., endogenous and exogenous lipids and proteins) over spatial areas,
      approximately 1 mm, with a spatial resolution of approximately 10-12 microm. In
      contrast, Raman microscopy allows the confocal examination of tissue at depths up
      to 100 microm with a pixel size of about 2-3 microm3. Spectral signal/noise,
      however, is reduced from IR and significantly smaller areas are generally
      monitored. The permeation of the gel phase DPPC-d62 was limited to approximately
      5-15 microm, whereas the liquid-crystalline phase P-d31OPC permeated to
      substantially greater depths (35-100 microm), at times ranging up to 24 h after
      application. The results are generally in accord with literature values. In
      addition, the state of the P-d31OPC (intact vesicles or molecularly dispersed
      with skin constituents) was evaluated from the spatial dependence of the
      deuteriopalmitate chain conformational order. Upon permeation, the chains became
      more ordered. The advantages and limitations of these imaging technologies are
      discussed.

PMID- 15737206
TI  - High invasive melanoma cells induce matrix metalloproteinase-1 synthesis in
      fibroblasts by interleukin-1alpha and basic fibroblast growth factor-mediated
      mechanisms.
AB  - Tumor invasion and metastasis of melanoma have been shown to require proteolytic
      degradation of the extracellular environment, achieved primarily by enzymes of
      the matrix metalloproteinases (MMP) family. Increased enzyme activity is
      localized at the border of tumor cells and the adjacent peritumoral connective
      tissue, emphasizing the crucial role of tumor-stroma interactions in the
      regulation of MMP activity. To analyze whether direct cell-cell contacts of
      melanoma cells and stromal fibroblasts or whether soluble factors, secreted by
      melanoma cells are involved in the regulation of MMP, we used different in vitro
      co-culture systems. Both direct and indirect co-cultures of high invasive BLM
      melanoma cells and human dermal fibroblasts resulted in an induction of pro-MMP-1
      synthesis. Medium conditioned by BLM cells strongly induced pro-MMP-1 synthesis
      in fibroblasts, indicating the importance of diffusible factors for this
      induction. Competition by recombinant human interleukin (IL)-1 receptor
      antagonist, neutralizing IL-1alpha and basic fibroblast growth factor (bFGF)
      antibodies, resulted in a concentration-dependent reduction of pro-MMP-1
      synthesis. Taken together, our results indicate an essential role for soluble
      factors, mainly IL-1alpha and bFGF, in the stimulation of dermal fibroblasts by
      human melanoma cells to secrete MMP-1.

PMID- 15737205
TI  - Quantification of melanoma micrometastases in sentinel lymph nodes using real
      time RT-PCR.
AB  - Detection of micrometastases in the regional tumor-draining lymph nodes is
      critical for staging and prognosis in melanoma patients. We applied a
      quantitative multiple-marker RT-PCR assay to improve the detection of occult
      melanoma cells in the sentinel lymph node (SLN). From 139 patients with primary
      cutaneous melanoma who underwent sentinel lymphadenectomy, a total of 235 SLN
      were assessed for Melan-A and tyrosinase expression by real-time quantitative RT
      PCR. Twenty-three patients (17%) were positive by histopathology and expressed
      messenger RNA of one or two markers. Of the patients with histopathologically
      negative SLN 39 (28%) were reclassified by positive RT-PCR. Patients were
      examined for tumor recurrences during a median follow-up period of 29 mo. Tumor
      recurrences were demonstrated in eight patients (35%) with histopathologically
      positive SLN, in four patients (10%) with submicroscopic tumor cells detected
      exclusively by real-time RT-PCR, and in none of the patients negative by both
      methods. The differences in recurrence rates were statistically significant
      (p=0.01). These data indicate that real-time quantitative RT-PCR for the
      detection of minimal residual melanoma in SLN improves the prediction of disease
      free survival.

PMID- 15737207
TI  - Ultraviolet A (320-400 nm) modulation of ultraviolet B (290-320 nm)-induced
      immune suppression is mediated by carbon monoxide.
AB  - Accumulating evidence suggests that suberythemogenic ultraviolet A (UVA) (320-400
      nm) exposure protects against the immunosuppressive effect of ultraviolet B (290
      320 nm) radiation or its epidermal photoproduct, cis-urocanic acid (cis-UCA). In
      skin, UVA photoimmunoprotection is mediated by the inducible antioxidant stress
      enzyme, heme oxygenase-1 (HO-1), which degrades heme into carbon monoxide (CO),
      iron, and biliverdin (reduced to bilirubin), and is important for cell survival
      under conditions of oxidative stress. The identity of the HO enzymatic product(s)
      that provide the immunoprotection is unknown. Here we examine the potential of CO
      to fulfill this role in hairless mouse skin, utilizing a novel CO-releasing
      molecule (CO-RM) to deliver CO to the skin topically. The CO-RM released CO
      gradually from the lotion vehicle during 3 h following its preparation, and
      between 50 and 500 microM, concentration-dependently protected mice against the
      suppression of contact hypersensitivity by either solar-simulated UV radiation
      (SSUVR) or cis-UCA, whereas aged CO-depleted CO-RM was inactive. Thus, the CO-RM
      treatment mimicked UVA-photoimmunoprotection, and identified HO-released CO as
      the protective mediator, providing evidence that the murine cutaneous immune
      system is modulated by this gaseous messenger. Preliminary evidence for
      involvement of guanylyl cyclase was obtained by treatment of the mouse with its
      specific inhibitor 1H-(1,2,4)oxadiazolo-(4,3-1)quinoxaline-1-one, which abrogated
      UVA photoimmunoprotection.

PMID- 15737208
TI  - Evidence for restricted Vbeta usage in the leukemic phase of cutaneous T cell
      lymphoma.
AB  - Antibodies directed against the beta chain of the T cell receptor (anti-Vbeta
      antibodies) are useful to identify the Vbeta repertoire of T cells in various
      diseases and to quantify numbers of Vbeta-bearing T cells. The goals of this
      study were to identify Vbeta+ cases of leukemic phase cutaneous T cell lymphoma
      (CTCL) and to compare the percentage of positive calls with other measures of
      blood tumor burden, i.e., lymphocyte subsets with a CD4+CD7- and CD4+CD26-
      phenotype and Sezary cell counts. Thirty-three of 49 (67%) cases of leukemic CTCL
      reacted with an anti-Vbeta antibody. When combined with reports from the
      literature, the frequency of Vbeta5 (probably Vbeta5.1) usage was relatively high
      when compared with Vbeta2 that is also frequently expressed by normal CD4+ T
      cells. The percentage of Vbeta+ cells correlated to the percentage of CD4+CD7-
      and CD4+CD26- cells for cases in which the neoplastic cells were deficient in
      expression of CD7 and CD26, respectively, but not the Sezary cell count. We
      hypothesize that the increased Vbeta5.1 usage in CTCL may be the result of
      depletion of Vbeta2 and other Vbeta-bearing T cells by staphylococcal
      superantigens prior to neoplastic transformation, resulting in a relative
      increase in the frequency of Vbeta5.1 usage in CTCL.

PMID- 15737209
TI  - Knowledge of body site variability in ultraviolet-induced erythemal responses
      guides choice of site for pre-therapy minimal erythema dose testing.

PMID- 15737211
TI  - Response to: mortality rate of bullous pemphigoid in a US medical center.

PMID- 15737212
TI  - Sepsis associated with dermatologic hospitalization is not the cause of high
      mortality of bullous pemphigoid in Europe.

PMID- 15737213
TI  - CD4+ CD56+ blastic tumor cells express CD101 molecules.

PMID- 15737214
TI  - Analysis of KIT, SCF, and initial screening of SLUG in patients with piebaldism.

PMID- 15737216
TI  - Nurses leading on patient safety.

PMID- 15737217
TI  - Impersonal trust and professional authority: exploring the dynamics.
AB  - AIM: The aim of the study was to explore the relationship between impersonal
      trust, governmentality and professional activity through an analysis of
      professional discourse. BACKGROUND: This study emerged from an earlier paper that
      described a four-dimensional model based on Luhmann's definition of trust as
      "reducing complexity and managing expectations". Linking trust with the
      Foucauldian notion of governmentality develops this further. Governmentality
      raises the question of how professional authority is constituted through the
      practice of nurses and other health and welfare professionals. METHOD: Discourse
      analysis was used to explore the text from two genres--academic literature and
      interview material (n = 17)--in the context of community residential services for
      people with learning disabilities. Findings. The study provided evidence to
      support claims that trust is produced through impersonal systems. Trust is
      contested in a dynamic process where there are gains and losses. Professionals in
      organisations actively promote trust, often through systems of distrust. The
      study also built on the four-dimensional model of impersonal trust--trust,
      mistrust, abuse and hope--and re-conceptualized the trust-hope dimension.
      CONCLUSION: There are theoretical links between governmentality and trust.
      Similarly, in order to understand trust nurses need to understand the dynamic
      nature of the systems in which they operate. The proposition that trust could
      frustrate hope adds an element of controversy to the discussion of hope in the
      nursing literature.

PMID- 15737218
TI  - Pressure ulcers: implementation of evidence-based nursing practice.
AB  - AIMS: A 2-year project was carried out to evaluate the use of multi-component,
      computer-assisted strategies for implementing clinical practice guidelines. This
      paper describes the implementation of the project and lessons learned. The
      evaluation and outcomes of implementing clinical practice guidelines to prevent
      and treat pressure ulcers will be reported in a separate paper. BACKGROUND: The
      prevalence and incidence rates of pressure ulcers, coupled with the cost of
      treatment, constitute a substantial burden for our health care system. It is
      estimated that treating a pressure ulcer can increase nursing time up to 50%, and
      that treatment costs per ulcer can range from US$10,000 to $86,000, with median
      costs of $27,000. Although evidence-based guidelines for prevention and optimum
      treatment of pressure ulcers have been developed, there is little empirical
      evidence about the effectiveness of implementation strategies. METHOD: The study
      was conducted across the continuum of care (primary, secondary and tertiary) in a
      Canadian urban Health Region involving seven health care organizations (acute,
      home and extended care). Trained surveyors (Registered Nurses) determined the
      prevalence and incidence of pressure ulcers among patients in these
      organizations. The use of a computerized decision-support system assisted staff
      to select optimal, evidence-based care strategies, record information and analyse
      individual and aggregate data. RESULTS: Evaluation indicated an increase in
      knowledge relating to pressure ulcer prevention, treatment strategies, resources
      required, and the role of the interdisciplinary team. Lack of visible senior
      nurse leadership; time required to acquire computer skills and to implement new
      guidelines; and difficulties with the computer system were identified as
      barriers. CONCLUSIONS: There is a need for a comprehensive, supported and
      sustained approach to implementation of evidence-based practice for pressure
      ulcer prevention and treatment, greater understanding of organization-specific
      barriers, and mechanisms for addressing the barriers.

PMID- 15737219
TI  - Acute coronary syndromes: cardiac rehabilitation programmes and quality of life.
AB  - AIMS: This paper reports a study examining the quality of life of clients
      following hospital admission with acute coronary syndrome in Hong Kong and their
      use of cardiac rehabilitation. BACKGROUND: Coronary heart disease is a major
      source of mortality and morbidity in Hong Kong. Western studies have suggested
      that participation in cardiac rehabilitation improves the quality of life of
      clients with coronary heart disease yet the use of cardiac rehabilitation has
      been reported to be low. Better understanding is needed of the psychosocial
      status of these clients in Hong Kong and their use of cardiac rehabilitation
      services. METHODS: A prospective, pretest-post-test study was carried out, with
      data collected over a period of 6 months with convenience sample of 182
      participants. Baseline data were obtained within one week after hospital
      admission for individuals experiencing ACS. The second phase of data collection
      commenced at 6 months after hospital discharge. Total period of data collection
      took over 12 months between 2002 and 2003. The Chinese version of the SF-36 was
      used to assess quality of life, and demographic data and the extent to which
      clients participated in the cardiac rehabilitation programme were assessed.
      RESULTS: Only 25% of the participants attended at least one session of the
      cardiac rehabilitation programme. Significant improvement occurred in all
      clients' perceived quality of life 6 months following initial hospital admission.
      No significant group differences in perceived quality of life were found
      according to whether or not clients used the cardiac rehabilitation services.
      CONCLUSION: Improvement in perceived health-related quality of life was evident
      over a 6-month period. Yet our findings suggested that participation in the
      cardiac rehabilitation programme did not have any apparent effects in subjects'
      perceived quality of life. Further studies using both generic and disease
      specific health-related quality of life instruments, as well as the inclusion of
      control group, are recommended. Continual improvement in cardiac rehabilitation
      programmes, and consideration of alternative modes of delivery other than the
      traditional attendance at hospital outpatient services, are also recommended.

PMID- 15737220
TI  - Lessons learned and advice from Vietnam war nurses: a qualitative study.
AB  - AIM: The aim of this paper is to describe guidance for nurses today from the
      lessons learned by nurses who served in the Vietnam War. BACKGROUND: There is
      little research focusing on nurses' experiences in the Vietnam War. Lessons
      learned and subsequent advice from nurses who served in Vietnam may be helpful to
      those serving in current and future wars. METHODS: A Husserlian phenomenological
      approach was taken, using interviews with a purposive sample of Registered Nurses
      who were female, and had served in the United States of America armed forces in
      Vietnam during the war. FINDINGS: Seven theme clusters described the lesson
      learned and guidance offered by the Vietnam War nurses: advice about journaling,
      training, caring for yourself, use of support systems, talking about your
      experiences, understanding the mission, and lack of preparation for war.
      CONCLUSIONS: Much can be learned from the lessons learned and advice given by
      Vietnam War nurses. These lessons stress that nurses need to take a pro-active
      role in preparing themselves for deployment to a war zone, and that institutional
      training for war needs to be intensive and realistic. The environmental,
      cultural, technological, clinical and psychosocial demands of war nursing need to
      be comprehensively addressed before nurses deploy to a war.

PMID- 15737221
TI  - Measuring neonatal intensive care unit-related parental stress.
AB  - AIMS: This paper reports a study: (1) to determine the validity and reliability
      of the Parent Stressor Scale:Neonatal Intensive Care Unit (PSS:NICU) for use with
      United Kingdom (UK) parents; (2) compare UK scores with those from a contemporary
      reference sample from the United States (US), (3) to identify the sources of
      greatest NICU-related stressors for parents and (4) to identify demographic or
      situational factors influencing NICU-related parental stress. BACKGROUND:
      Evaluation of the adequacy of nursing care and psychosocial support services for
      parents of ill infants in the NICU requires valid and reliable measures of
      parental stress. The PSS:NICU is a well-validated scale developed in the US to
      measure NICU-related parental stress. However, it has not been tested in the UK.
      METHODS: Consecutive samples of parents (n = 257) of infants in nine UK NICUs and
      two reference US units completed the PSS:NICU and the Spielberger State-Trait
      Anxiety Scale approximately 1 week after admission. Psychometric properties of
      the PSS:NICU, including internal consistency reliability and construct,
      concurrent and predictive validity, were evaluated. RESULTS: PSS:NICU scores were
      similar in the UK and US samples and high internal consistency reliability was
      found for all metrics (e.g. Overall Stress: 0.94 for both samples). A three
      factor principal components solution accounted for 66% of the variance in the
      scores, with the items grouped into the three a priori scales specified in the
      PSS:NICU (Infant Behaviour and Appearance, Parental Role Alterations, and Sights
      and Sounds). Stress Occurrence and Overall Stress were moderately correlated with
      State Anxiety in both samples (r = 0.46-0.61, P < 0.001). Thirty-one per cent of
      the variance in Stress Occurrence in the UK sample was explained by State
      Anxiety, infant severity of illness score, parent gender, and less frequent
      visitation. CONCLUSIONS: The PSS:NICU demonstrated appropriate psychometrics in a
      large sample of parents from diverse NICUs in the UK. These findings support its
      wider use in research and clinical practice to identify parental distress and
      evaluate the effectiveness of nursing care and psychosocial support services for
      parents.

PMID- 15737222
TI  - Men and health help-seeking behaviour: literature review.
AB  - AIM: This paper reviews the key research literature regarding men's health
      related help seeking behaviour. BACKGROUND: There is a growing body of research
      in the United States to suggest that men are less likely than women to seek help
      from health professionals for problems as diverse as depression, substance abuse,
      physical disabilities and stressful life events. Previous research has revealed
      that the principle health related issue facing men in the UK is their reluctance
      to seek access to health services. METHOD: The investigation of men's health
      related help seeking behaviour has great potential for improving both men and
      women's lives and reducing national health costs through the development of
      responsive and effective interventions. A search of the literature was conducted
      using CINAHL, MEDLINE, EMBASE, PsychINFO and the Cochrane Library databases.
      RESULTS: Studies comparing men and women are inadequate in explaining the
      processes involved in men's help seeking behaviour. However, the growing body of
      gender-specific studies highlights a trend of delayed help seeking when they
      become ill. A prominent theme among white middle class men implicates
      "traditional masculine behaviour" as an explanation for delays in seeking help
      among men who experience illness. The reasons and processes behind this issue,
      however, have received limited attention. CONCLUSIONS: Principally, the role of
      masculine beliefs and the similarities and differences between men of differing
      background requires further attention, particularly given the health inequalities
      that exist between men of differing socio-economic status and ethnicity. Further
      research using heterogeneous samples is required in order to gain a greater
      understanding of the triggers and barriers associated with the decision making
      process of help seeking behaviour in men who experience illness.

PMID- 15737223
TI  - The role of nurses in preventing adverse events related to respiratory
      dysfunction: literature review.
AB  - AIMS: This paper reports a literature review examining the relationship between
      specific clinical indicators of respiratory dysfunction and adverse events, and
      exploring the role of nurses in preventing adverse events related to respiratory
      dysfunction. BACKGROUND: Adverse events in hospital are associated with poor
      patient outcomes such as increased mortality and permanent disability. Many of
      these adverse events are preventable and are preceded by a period during which
      the patient exhibits clearly abnormal physiological signs. The role of nurses in
      preserving physiological safety by early recognition and correction of
      physiological abnormality is a key factor in preventing adverse events. METHODS:
      A search of the Medline and CINAHL databases was conducted using the following
      terms: predictors of poor outcome, adverse events, mortality, cardiac arrest,
      emergency, oxygen, supplemental oxygen, oxygen therapy, oxygen saturation, oxygen
      delivery, assessment, patient assessment, physical assessment, dyspnoea, hypoxia,
      hypoxaemia, respiratory assessment, respiratory dysfunction, shortness of breath
      and pulse oximetry. The papers reviewed were research papers that demonstrated a
      relationship between adverse events and various clinical indicators of
      respiratory dysfunction. RESULTS: Respiratory dysfunction is a known clinical
      antecedent of adverse events such as cardiac arrest, need for medical emergency
      team activation and unplanned intensive care unit admission. The presence of
      respiratory dysfunction prior to an adverse event is associated with increased
      mortality. The specific clinical indicators involved are alterations in
      respiratory rate, and the presence of dyspnoea, hypoxaemia and acidosis.
      CONCLUSIONS: The way in which nurses assess, document and use clinical indicators
      of respiratory dysfunction is influential in identifying patients at risk of an
      adverse event and preventing adverse events related to respiratory dysfunction.
      If such adverse events are to be prevented, nurses must not only be able to
      recognise and interpret signs of respiratory dysfunction, but must also take
      responsibility for initiating and evaluating interventions aimed at correcting
      respiratory dysfunction.

PMID- 15737224
TI  - Healthy living interventions and schizophrenia: a systematic review.
AB  - AIM: This paper reports a systematic review of the published and grey literature
      which has investigated the efficacy of healthy living interventions for adults
      with a diagnosis of schizophrenia or schizo-affective disorder. BACKGROUND:
      Adults with a diagnosis of schizophrenia or schizo-affective disorder have
      reduced life expectancy when compared with members of the general population,
      with approximately 59% of excess mortality resulting from natural causes.
      METHODS: The review was conducted following guidelines provided by the United
      Kingdom National Health Service Centre for Reviews and Dissemination, and using
      the Medline, PsycINFO, CINAHL, Embase, Cochrane Library, National Research
      Register, and System for Info on Grey Literature databases. RESULTS: Sixteen
      studies were identified, examining four types of healthy living interventions:
      smoking cessation (n = 7), weight management (n = 5), exercise (n = 3) and
      nutritional education (n = 1). The smoking cessation, weight management and
      exercise studies showed positive outcomes in the main. The quality of the
      studies, however, was generally poor. Only two had control groups, most recruited
      small self-selected samples, six did not standardize for diagnosis, external
      validity was generally poor and no studies followed participants for longer than
      6 months. The best quality evidence was produced by the smoking cessation and
      weight management studies, which were more methodologically robust and
      demonstrated promising outcomes. CONCLUSIONS: Further research is needed to
      assist the development of effective interventions to help this client group to
      adopt and maintain healthier lifestyles. Research and practice development in
      this area may be an important role for nurses in both hospital and community
      settings.

PMID- 15737225
TI  - Improving the psychosocial work environment.
AB  - AIM: This paper reports a pilot project to evaluate the effectiveness of a
      participatory organizational intervention to improve the psychosocial work
      environment in one long-term care unit. BACKGROUND: Since the early 1990s, health
      care institutions in Quebec have been constantly changing in order to improve the
      efficiency of the health care system. These changes have affected the work
      environment and have contributed to higher rates of burnout and absenteeism among
      nurses and other health care workers. METHOD: The study participants were health
      care workers in a long-term care unit (n = 60). The participatory organizational
      intervention was based on a contract and carried out by a work team. Work
      constraints were identified, and an action plan implemented, The effectiveness of
      the intervention was evaluated by pre- and postintervention questionnaires: the
      Job Content Questionnaire, Effort-Reward Imbalance Questionnaire and Psychiatric
      Symptom Index. RESULTS: There was a significant increase in reward (P < or =
      0.01) and a significant decrease in Effort-Reward Imbalance (P < or = 0.01)
      following the intervention. Absenteeism rates decreased from 8.26% to 1.86% over
      the study period, but in the rest of the institution remained the same. However,
      there was a significant decrease in social support from supervisors (P < 0.05) at
      post-test. CONCLUSION: Participation by health care workers and action plans
      targeting problematic aspects of the psychosocial work environment are key
      elements in interventions to improve their health. However, such interventions
      present challenges, such as the involvement of managers, involvement of all
      relevant participants, and re-establishment of trust within work teams.
      Recognition and respect must be re-established, and supervisors must engage with
      health care workers and give support at all stages of the intervention.

PMID- 15737226
TI  - Integrating environmental health into nursing and midwifery practice.
AB  - AIM: With the recognition that environmental health has relevance to all nursing
      and midwifery activities, the aim of this paper is to discuss nurses' and
      midwives' past and present involvement in environmental health in the UK, where
      the international situation demonstrates good practice, and the challenges and
      possibilities for greater and more effective UK-based activity in the future.
      BACKGROUND: The association between environmental hazards and adverse health
      effects has received increasing attention over recent years. In the United States
      of America (USA), the importance of developing an environmental health role for
      nurses outside of the "traditional" occupational and environmental health nursing
      specialty has been recognized and acted upon through education, information
      programmes and policy developments. In the United Kingdom (UK), the same degree
      of interest, commitment and activity is somewhat lacking. DISCUSSION: Little
      nursing and midwifery activity on environmental health issues has taken place in
      the UK over recent years. The lack of development in this field may relate to the
      problems of an already overstretched disease treatment service and the lack of an
      upstream approach to public health. Theoretical and philosophical influences, as
      well as individual and organizational obstacles or constraints, exist and may
      hinder nurses and midwives in their efforts to address the subject. Yet nurses
      and midwives are the largest group in the National Health Service workforce and
      this gives enormous potential for effective interventions in environmental
      health. CONCLUSIONS: Whilst barriers and obstacles to nursing and midwifery
      involvement in environmental health in the UK exist, they are all surmountable
      and appropriate interventions could prove cost-effective in the middle and long
      term. Additionally, they may be viewed as a necessary activity for nurses and
      midwives in response to real health threats and the expressed worries and
      concerns of patients and communities.

PMID- 15737227
TI  - The impact of research governance in healthcare and higher education
      organizations.
AB  - AIM: This paper reports a study exploring the impact and implementation of
      research governance in the North West region of England. BACKGROUND: In 2001, the
      UK Government launched a framework to ensure the governance of research within
      the National Health Service. Whilst this framework was undoubtedly geared towards
      improving the standards and practice of research, concerns have been raised in
      the academic literature about the potentially negative impact on future research.
      METHODS: A mixed method approach, using questionnaires (n = 350), semi-structured
      interviews and focus groups with a volunteer sample, was used to explore research
      staff perspectives about research governance. Survey data were analysed using
      Microsoft Excel, and a thematic analysis was used to elicit themes from the semi
      structured interviews. The study lasted for 12 months and used a range of study
      sites, giving insight into potentially different experiences or approaches to
      implementing the research governance framework. FINDINGS: Questionnaire data
      revealed a good level of awareness about the Research Governance Framework.
      However, a range of concerns was also raised, such as the increased workload
      associated with the research governance application process and lack of
      transparency about the process. Five themes emerged from the focus groups:
      control, epistemology, organizational issues, impact on teaching and learning,
      and ambiguity in the definitions of research and audit. CONCLUSIONS:
      Recommendations emerging from the study include the promotion of transparent
      research governance guidelines for practitioners, and the need for staff
      education about governance processes and greater parity between organizations in
      research governance processes.

PMID- 15737232
TI  - Measurement of fractionated plasma metanephrines for exclusion of
      pheochromocytoma: Can specificity be improved by adjustment for age?
AB  - BACKGROUND: Biochemical testing for pheochromocytoma by measurement of
      fractionated plasma metanephrines is limited by false positive rates of up to 18%
      in people without known genetic predisposition to the disease. The plasma
      normetanephrine fraction is responsible for most false positives and plasma
      normetanephrine increases with age. The objective of this study was to determine
      if we could improve the specificity of fractionated plasma measurements, by
      statistically adjusting for age. METHODS: An age-adjusted metanephrine score was
      derived using logistic regression from 343 subjects (including 33 people with
      pheochromocytoma) who underwent fractionated plasma metanephrine measurements as
      part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester
      (derivation set). The performance of the age-adjusted score was validated in a
      dataset of 158 subjects (including patients 23 with pheochromocytoma) that
      underwent measurements of fractionated plasma metanephrines at Mayo Clinic the
      following year (validation dataset). None of the participants in the validation
      dataset had known genetic predisposition to pheochromocytoma. RESULTS: The
      sensitivity of the age-adjusted metanephrine score was the same as that of
      traditional interpretation of fractionated plasma metanephrine measurements,
      yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%).
      However, the false positive rate with traditional interpretation of fractionated
      plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and
      that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI,
      1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age
      in the interpretation of results of fractionated plasma metanephrines may
      significantly decrease false positives when using this test to exclude sporadic
      pheochromocytoma. Such improvements in false positive rate may result in savings
      of expenditures related to confirmatory imaging.

PMID- 15737233
TI  - Phosphorylation of HIV Tat by PKR increases interaction with TAR RNA and enhances
      transcription.
AB  - BACKGROUND: The interferon (IFN)-induced, dsRNA-dependent serine/threonine
      protein kinase, PKR, plays a key regulatory role in the IFN-mediated anti-viral
      response by blocking translation in the infected cell by phosphorylating the
      alpha subunit of elongation factor 2 (eIF2). The human immunodeficiency virus
      type 1 (HIV-1) evades the anti-viral IFN response through the binding of one of
      its major transcriptional regulatory proteins, Tat, to PKR. HIV-1 Tat acts as a
      substrate homologue for the enzyme, competing with eIF2alpha, and inhibiting the
      translational block. It has been shown that during the interaction with PKR, Tat
      becomes phosphorylated at three residues: serine 62, threonine 64 and serine 68.
      We have investigated the effect of this phosphorylation on the function of Tat in
      viral transcription. HIV-1 Tat activates transcription elongation by first
      binding to TAR RNA, a stem-loop structure found at the 5' end of all viral
      transcripts. Our results showed faster, greater and stronger binding of Tat to
      TAR RNA after phosphorylation by PKR. RESULTS: We have investigated the effect of
      phosphorylation on Tat-mediated transactivation. Our results showed faster,
      greater and stronger binding of Tat to TAR RNA after phosphorylation by PKR. In
      vitro phosphorylation experiments with a series of bacterial expression
      constructs carrying the wild-type tat gene or mutants of the gene with alanine
      substitutions at one, two, or all three of the serine/threonine PKR
      phosphorylation sites, showed that these were subject to different levels of
      phosphorylation by PKR and displayed distinct kinetic behaviour. These results
      also suggested a cooperative role for the phosphorylation of S68 in conjunction
      with S62 and T64. We examined the effect of phosphorylation on Tat-mediated
      transactivation of the HIV-1 LTR in vivo with a series of analogous mammalian
      expression constructs. Co-transfection experiments showed a gradual reduction in
      transactivation as the number of mutated phosphorylation sites increased, and a 4
      fold decrease in LTR transactivation with the Tat triple mutant that could not be
      phosphorylated by PKR. Furthermore, the transfection data also suggested that the
      presence of S68 is necessary for optimal Tat-mediated transactivation.
      CONCLUSION: These results support the hypothesis that phosphorylation of Tat may
      be important for its function in HIV-1 LTR transactivation.

PMID- 15737234
TI  - Placentation in the paca (Agouti paca L).
AB  - BACKGROUND: The paca is a South American rodent with potential as a commercial
      food animal. We examined paca placenta as part of a wider effort to understand
      the reproductive biology of this species. METHODS: Thirteen specimens between
      midgestation and term of pregnancy were studied by light and transmission
      electron microscopy. RESULTS: The placenta is divided into several lobes
      separated by interlobular trophoblast. Maternal arterial channels and fetal veins
      are found at the centre of each lobe. In the labyrinth, maternal blood flows
      through trophoblast-lined lacunae in close proximity to the fetal capillaries.
      The interhaemal barrier is of the haemomonochorial type with a single layer of
      syncytiotrophoblast. Caveolae occur in the apical membrane of the
      syncytiotrophoblast and recesses in the basal membrane, but there is no evidence
      of transtrophoblastic channels. The interlobular areas consist of cords of
      syncytiotrophoblast defining maternal blood channels that drain the labyrinth.
      Yolk sac endoderm covers much of the fetal surface of the placenta. The
      subplacenta comprises cytotrophoblast and syncytiotrophoblast. There are dilated
      intercellular spaces between the cytotrophoblasts and lacunae lined by
      syncytiotrophoblast. In the junctional zone between subplacenta and decidua,
      there are nests of multinucleated giant cells with vacuolated cytoplasm. The
      entire placenta rests on a pedicle of maternal tissue. An inverted yolk sac
      placenta is also present. The presence of small vesicles and tubules in the
      apical membrane of the yolk sac endoderm and larger vesicles in the supranuclear
      region suggest that the yolk sac placenta participates in maternal-fetal transfer
      of protein. CONCLUSION: The paca placenta closely resembles that of other
      hystricomorph rodents. The lobulated structure allows for a larger exchange area
      and the development of precocial young.

PMID- 15737235
TI  - Ethical challenges in surgery as narrated by practicing surgeons.
AB  - BACKGROUND: The aim of this study was to explore the ethical challenges in
      surgery from the surgeons' point of view and their experience of being in
      ethically difficult situations. METHODS: Five male and five female surgeons at a
      university hospital in Norway were interviewed as part of a comprehensive
      investigation into the narratives of nurses and physicians about being in such
      situations. The transcribed interview texts were subjected to a phenomenological
      hermeneutic interpretation. RESULTS: No differences in ethical reasoning between
      male and female surgeons were found. They reasoned in both action and relational
      ethical perspectives. Surgeons focused on their relationships with patients and
      colleagues and their moral self in descriptions of the ethical challenges in
      their work. Dialogue and personal involvement were important in their
      relationships with patients. The surgeons emphasized the importance of open
      dialogue, professional recognition, and an inclusive and accepting environment
      between colleagues. CONCLUSION: The surgeons are personally challenged by the
      existential realities of human life in their relationships with patients. They
      realized that ethical challenges are an inherent part of performing surgery and
      of life itself, and say that they have to learn to "live with" these challenges
      in a way that is confirmed both socially and by their inner moral self. This
      means accepting their personal and professional limitations, being uncertain,
      being fallible, and being humble. Living with the ethical challenges of surgery
      seems to contribute to the surgeons' confidence and vulnerability in their
      professional identity.

PMID- 15737236
TI  - Food selection associated with sense of coherence in adults.
AB  - BACKGROUND: Favorable dietary habits promote health, whereas unfavorable habits
      link to various chronic diseases. An individual's "sense of coherence" (SOC) is
      reported to correlate with prevalence of some diseases to which dietary habits
      are linked. However, understanding what determines an individual's dietary
      preferences and how to change his/her behavior remains limited. The aim of the
      present study was to evaluate associations between dietary intake and SOC in
      adults. METHODS: Diet intake was recorded by an 84-item semi-quantitative food
      frequency questionnaire and SOC was measured by the 13-item Antonovsky
      questionnaire in 2,446 men and 2,545 women (25-74 years old) from the population
      based northern Sweden MONICA screening in 1999. RESULTS: Intakes of energy, total
      and saturated fat, ascorbic acid, sucrose, and servings of fruits, vegetables,
      cereals, and sweets correlated with SOC among women, whereas intakes of total and
      saturated fat, ascorbic acid, fiber, and alcohol, and servings of fruits,
      vegetables, bread, bread and cereals, fish, and potatoes correlated with SOC
      among men. With a few exceptions, intakes of these nutrients/foods were
      significantly explained by SOC quartile scores in linear GLM models. Both women
      and men classified into the highest SOC quartile had significantly higher age-BMI
      education standardized mean intakes of vegetables than those in the lowest
      quartiles. Women in the highest SOC quartile also had higher intake of fruits but
      lower intakes of energy, total and saturated fat, sucrose, and sweets. Projection
      to latent structures (PLS) multivariate modeling of intakes of the 84 food items
      and food aggregates simultaneously on SOC scores supported low SOC to coincide
      with a presumably less health promoting dietary preference, e.g. intake of pizza,
      soft drinks, candies, sausages for main course, hamburgers, mashed potato, chips
      and other snacks, potato salad, French fries, whereas men and women with high SOC
      scores were characterized by e.g. high intake of rye crisp whole meal bread,
      boiled potato, vegetables, berries, and fruits. CONCLUSION: Both men and women in
      the highest, as compared with the lowest, SOC score quartile reported more
      "healthy" food choices. Dietary habits for individuals in the lowest SOC quartile
      therefore may render a higher risk for various endemic diseases.

PMID- 15737238
TI  - Aggressive HIV-1?
AB  - New York City health officials announced on February 11, 2005 that a patient
      rapidly developed full-blown AIDS shortly after being diagnosed with a rare, drug
      resistant strain of HIV-1. The New York City Department of Health issued an alert
      to all hospitals and doctors and a press conference was held to announce the
      emergence of an aggressive HIV-1 strain that may be difficult to treat and that
      appears to trigger rapid progression to AIDS. Is the panic justified?

PMID- 15737239
TI  - L-histidine inhibits production of lysophosphatidic acid by the tumor-associated
      cytokine, autotaxin.
AB  - BACKGROUND: Autotaxin (ATX, NPP-2), originally purified as a potent tumor cell
      motility factor, is now known to be the long-sought plasma lysophospholipase D
      (LPLD). The integrity of the enzymatic active site, including three crucial
      histidine moieties, is required for motility stimulation, as well as LPLD and
      5'nucleotide phosphodiesterase (PDE) activities. Except for relatively non
      specific chelation agents, there are no known inhibitors of the ATX LPLD
      activity. RESULTS: We show that millimolar concentrations of L-histidine inhibit
      ATX-stimulated but not LPA-stimulated motility in two tumor cell lines, as well
      as inhibiting enzymatic activities. Inhibition is reversed by 20-fold lower
      concentrations of zinc salt. L-histidine has no significant effect on the Km of
      LPLD, but reduces the Vmax by greater than 50%, acting as a non-competitive
      inhibitor. Several histidine analogs also inhibit the LPLD activity of ATX;
      however, none has greater potency than L-histidine and all decrease cell
      viability or adhesion. CONCLUSION: L-histidine inhibition of LPLD is not a simple
      stoichiometric chelation of metal ions but is more likely a complex interaction
      with a variety of moieties, including the metal cation, at or near the active
      site. The inhibitory effect of L-histidine requires all three major functional
      groups of histidine: the alpha amino group, the alpha carboxyl group, and the
      metal-binding imidazole side chain. Because of LPA's involvement in pathological
      processes, regulation of its formation by ATX may give insight into possible
      novel therapeutic approaches.

PMID- 15737240
TI  - Negative density-distribution relationship in butterflies.
AB  - BACKGROUND: Because "laws of nature" do not exist in ecology, much of the
      foundations of community ecology rely on broad statistical generalisations. One
      of the strongest generalisations is the positive relationship between density and
      distribution within a given taxonomic assemblage; that is, locally abundant
      species are more widespread than locally sparse species. Several mechanisms have
      been proposed to create this positive relationship, and the testing of these
      mechanisms is attracting increasing attention. RESULTS: We report a strong, but
      counterintuitive, negative relationship between density and distribution in the
      butterfly fauna of Finland. With an exceptionally comprehensive data set (data
      includes all 95 resident species in Finland and over 1.5 million individuals), we
      have been able to submit several of the mechanisms to powerful direct empirical
      testing. Without exception, we failed to find evidence for the proposed
      mechanisms creating a positive density-distribution relationship. On the
      contrary, we found that many of the mechanisms are equally able to generate a
      negative relationship. CONCLUSION: We suggest that one important determinant of
      density-distribution relationships is the geographical location of the study: on
      the edge of a distribution range, suitable habitat patches are likely to be more
      isolated than in the core of the range. In such a situation, only the largest and
      best quality patches are likely to be occupied, and these by definition can
      support a relatively dense population leading to a negative density-distribution
      relationship. Finally, we conclude that generalizations about the positive
      density-distribution relationship should be made more cautiously.

PMID- 15737241
TI  - Reduction of motion artifact in pulse oximetry by smoothed pseudo Wigner-Ville
      distribution.
AB  - BACKGROUND: The pulse oximeter, a medical device capable of measuring blood
      oxygen saturation (SpO2), has been shown to be a valuable device for monitoring
      patients in critical conditions. In order to incorporate the technique into a
      wearable device which can be used in ambulatory settings, the influence of motion
      artifacts on the estimated SpO2 must be reduced. This study investigates the use
      of the smoothed psuedo Wigner-Ville distribution (SPWVD) for the reduction of
      motion artifacts affecting pulse oximetry. METHODS: The SPWVD approach is
      compared with two techniques currently used in this field, i.e. the weighted
      moving average (WMA) and the fast Fourier transform (FFT) approaches. SpO2 and
      pulse rate were estimated from a photoplethysmographic (PPG) signal recorded when
      subject is in a resting position as well as in the act of performing four types
      of motions: horizontal and vertical movements of the hand, and bending and
      pressing motions of the finger. For each condition, 24 sets of PPG signals
      collected from 6 subjects, each of 30 seconds, were studied with reference to the
      PPG signal recorded simultaneously from the subject's other hand, which was
      stationary at all times. RESULTS AND DISCUSSION: The SPWVD approach shows
      significant improvement (p < 0.05), as compared to traditional approaches, when
      subjects bend their finger or press their finger against the sensor. In addition,
      the SPWVD approach also reduces the mean absolute pulse rate error significantly
      (p < 0.05) from 16.4 bpm and 11.2 bpm for the WMA and FFT approaches,
      respectively, to 5.62 bpm. CONCLUSION: The results suggested that the SPWVD
      approach could potentially be used to reduce motion artifact on wearable pulse
      oximeters.

PMID- 15737242
TI  - Preventing complicated transseptal puncture with intracardiac echocardiography:
      case report.
AB  - BACKGROUND: Recently, intracardiac echocardiography emerged as a useful tool in
      the electrophysiology laboratories for guiding transseptal left heart
      catheterizations, for avoiding thromboembolic and mechanical complications and
      assessing the ablation lesions characteristics. Although the value of ICE is well
      known, it is not a universal tool for achieving uncomplicated access to the left
      atrium. We present a case in which ICE led to interruption of a transseptal
      procedure because several risk factors for mechanical complications were
      revealed. CASE PRESENTATION: A case of a patient with paroxysmal atrial
      fibrillation and atrial flutter, and distorted intracardiac anatomy is presented.
      Intracardiac echocardiography showed a small oval fossa abouting to an enlarged
      aorta anteriorly. A very small distance from the interatrial septum to the left
      atrial free wall was seen. The latter two conditions were predisposing to a
      complicated transseptal puncture. According to fluoroscopy the transseptal needle
      had a correct position, but the intracardiac echo image showed that it was
      actually pointing towards the aortic root and most importantly, that it was
      virtually impossible to stabilize it in the fossa itself. Based on intracardiac
      echo findings a decision was made to limit the procedure only to ablation of the
      cavotricuspid isthmus and not to proceed further so as to avoid complications.
      CONCLUSION: This case report illustrates the usefulness of the intracardiac
      echocardiography in preventing serious or even fatal complications in transseptal
      procedures when the cardiac anatomy is unusual or distorted. It also helps to
      understand the possible mechanisms of mechanical complications in cases where
      fluoroscopic images are apparently normal.

PMID- 15737243
TI  - Peak pressures during manual ventilation.
AB  - INTRODUCTION: Manual (bag) ventilation sometimes achieves better oxygenation than
      does a mechanical ventilator. We speculated that clinicians might generate very
      high airway pressure during manual ventilation (much higher than the pressure
      delivered by a mechanical ventilator), and that the high airway pressure causes
      alveolar recruitment and thus improves oxygenation. Such high pressure might
      injure alveoli in some patients. METHODS: We tested the hypothesis that manual
      ventilation may involve substantially higher pressure than is delivered by a
      mechanical ventilator. We asked experienced respiratory therapists to manually
      ventilate a lung model that was set to represent several typical clinical
      scenarios. RESULTS: We found that the peak airway pressure generated by the
      therapists was sometimes in excess of 100 cm H(2)O. CONCLUSIONS: The high airway
      pressure during manual ventilation would be considered extreme in the context of
      conventional mechanical ventilation, which raises questions about whether manual
      ventilation causes barotrauma.

PMID- 15737244
TI  - The impact of closed endotracheal suctioning systems on mechanical ventilator
      performance.
AB  - BACKGROUND: Closed endotracheal suctioning during mechanical ventilation is
      increasingly used, but its impact on ventilator function has not been fully
      studied. METHODS: We evaluated the impact of closed suctioning with 11 critical
      care ventilators, during assisted ventilation in pressure-support mode, pressure
      assist/control mode, volume-assist/control mode, and during continuous positive
      airway pressure, with 2 suctioning pressures (-120 mm Hg and approximately -200
      mm Hg), and with 2 tidal volumes (450 mL and 900 mL). We continuously measured
      airway pressure, flow at the airway, and pressure distal to the catheter tip,
      before, during, and after a single 15-second period of continuous suctioning.
      RESULTS: No ventilator malfunctioned as a result of the closed suctioning. During
      suctioning, end-expiratory pressure markedly decreased in all modes, and peak
      flow increased in all modes except volume-assist/control (p < 0.001). Respiratory
      rate increased during suctioning in pressure- and volume-assist/control (p <
      0.001) but not during pressure support or continuous positive airway pressure.
      Gas delivery was most altered during volume-assist/control with the smaller tidal
      volume (p < 0.05) and least altered during pressure-assist/control with the
      larger tidal volume. CONCLUSION: There are large differences between the
      ventilators evaluated (p < 0.001). Closed suctioning does not cause mechanical
      ventilator malfunction. Upon removal of the suction catheter, these ventilators
      resumed their pre-suctioning-procedure gas delivery within 2 breaths, and, during
      all the tested modes, all the ventilators maintained gas delivery. However,
      closed suctioning can decrease end-expiratory pressure during suctioning.

PMID- 15737245
TI  - A laboratory evaluation of 2 mechanical ventilators in the presence of helium
      oxygen mixtures.
AB  - BACKGROUND: Helium-oxygen (heliox) mixtures are being used more frequently with
      mechanical ventilators. Newer ventilators continue to be developed that have not
      yet been evaluated for safety and efficacy of heliox delivery. We studied the
      performance of 2 previously untested ventilators (Servo-i and Inspiration) during
      heliox administration. METHODS: We measured tidal volume (V(T)) delivery, gas
      blending, gas analyzing, and pressure stability in the presence of heliox. A
      heliox (80% helium/20% oxygen) tank was attached to the 50-psi air inlet. We
      compared the set V(T) (ie, set on the ventilator) and the exhaled V(T) (measured
      by the ventilator) to the delivered V(T) (measured with a lung model). Pressure
      measurements were also evaluated. We also compared the ventilator-setting
      fraction of inspired oxygen (F(IO(2))) to the F(IO(2)) measured by the ventilator
      and the F(IO(2)) measured with a supplemental oxygen analyzer. RESULTS: Heliox
      significantly affected both the exhaled V(T) measurement and the actual delivered
      V(T) (p < 0.001) with both the Servo-i and the Inspiration. Neither peak
      inspiratory pressure (in the pressure-controlled ventilation mode) nor positive
      end-expiratory pressure were adversely affected by heliox with either ventilator.
      Introducing heliox into the gas-blending systems caused only a small error in
      F(IO2) delivery and monitoring. CONCLUSIONS: Both Ventilators cycled consistently
      with heliox mixtures. In most cases, actual delivered V(T) can be reliably
      calculated if the F(IO2) and the set V(T) or the measured exhaled V(T) is known.
      With the Servo-i, at high helium concentrations the exhaled V(T) measurement was
      unreliable and caused a high-priority alarm condition that couldn't be disabled.
      A supplemental oxygen analyzer is not necessary with either device for heliox
      applications.

PMID- 15737246
TI  - Carbon dioxide elimination and gas displacement vary with piston position during
      high-frequency oscillatory ventilation.
AB  - INTRODUCTION: Alterations in gas displacement in pediatric patients ventilated
      with the SensorMedics 3100A high-frequency oscillator are most commonly
      manipulated by adjusting the amplitude, frequency, and percent inspiratory time.
      The piston-position-and-displacement indicator is commonly centered and
      subsequently not adjusted. That practice may limit the clinician's ability to
      optimize carbon dioxide elimination. We hypothesized that varying the piston
      position would alter gas displacement and carbon dioxide elimination. METHODS: We
      conducted an observational study in a tertiary pediatric intensive care unit and
      a correlated bench study. In the clinical study, 24 patients were ventilated with
      a SensorMedics 3100A high-frequency oscillator. Transcutaneously measured carbon
      dioxide ((tCO(2))) values were documented with the piston-position-and
      displacement indicator in left, center, and right positions. In the bench study
      the oscillator was set and maintained at: mean airway pressure 15 cm H(2)O,
      inspiratory time 33% of respiratory-cycle time, bias flow 20 L/min. A
      pneumotachometer attached to a respiratory mechanics monitor was placed between
      the ventilator circuit and a test lung. Data were collected with the piston
      position-and-displacement indicator at the left, center, and right positions with
      frequencies of 4-14 Hz and amplitudes of 25-55 cm H(2)O. Data were collected over
      a 3-minute time period for each combination of frequency, amplitude, and piston
      position-and-displacement-indicator position. We compared the data with repeated
      measures analysis of variance. Pairwise comparisons were performed with a 2
      tailed Student's test with Bonferroni correction. RESULTS: Among the 24 patients
      (tCO(2)) was significantly associated with the position of the piston (p <
      0.007). In the bench study, gas displacement was higher when the piston-position
      and-displacement indicator was positioned to the left (than when at the center
      position) 91.7% of the time (p < 0.0001). When the piston-position-and
      displacement indicator was positioned to the right (as compared to the center
      position), gas displacement was lower 75% of the time (p < 0.0001). CONCLUSION:
      Adjusting the oscillator piston alters the volume of gas displaced and provides
      an additional means for titrating carbon dioxide elimination. .

PMID- 15737247
TI  - The inhalation of drugs: advantages and problems.
AB  - Inhalation is a very old method of drug delivery, and in the 20th century it
      became a mainstay of respiratory care, known as aerosol therapy. Use of inhaled
      epinephrine for relief of asthma was reported as early as 1929, in England. An
      early version of a dry powder inhaler (DPI) was the Aerohalor, used to administer
      penicillin dust to treat respiratory infections. In the 1950s, the Wright
      nebulizer was the precursor of the modern hand-held jet-venturi nebulizer. In
      1956, the first metered-dose inhaler (MDI) was approved for clinical use,
      followed by the SpinHaler DPI for cromolyn sodium in 1971. The scientific basis
      for aerosol therapy developed relatively late, following the 1974 Sugarloaf
      Conference on the scientific basis of respiratory therapy. Early data on the drug
      delivery efficiency of the common aerosol delivery devices (MDI, DPI, and
      nebulizer) showed lung deposition of approximately 10-15% of the total, nominal
      dose. Despite problems with low lung deposition with all of the early devices,
      evidence accumulated that supported the advantages of the inhalation route over
      other drug-administration routes. Inhaled drugs are localized to the target
      organ, which generally allows for a lower dose than is necessary with systemic
      delivery (oral or injection), and thus fewer and less severe adverse effects. The
      3 types of aerosol device (MDI, DPI, and nebulizer) can be clinically equivalent.
      It may be necessary to increase the number of MDI puffs to achieve results
      equivalent to the larger nominal dose from a nebulizer. Design and lung
      deposition improvement of MDIs, DPIs, and nebulizers are exemplified by the new
      hydrofluoroalkane-propelled MDI formulation of beclomethasone, the metered-dose
      liquid-spray Respimat, and the DPI system of the Spiros. Differences among
      aerosol delivery devices create challenges to patient use and caregiver
      instruction. Potential improvements in aerosol delivery include better
      standardization of function and patient use, greater reliability, and reduction
      of drug loss.

PMID- 15737248
TI  - Clozapine, risperidone, olanzapine, and conventional antipsychotic drug effects
      on glucose, lipids, and leptin in schizophrenic patients.
AB  - Some reports have indicated increased rates of diabetes and increased prevalence
      of glucose and lipid abnormalities during treatment with second-generation
      antipsychotics, with most concern raised about clozapine and olanzapine. Most of
      the findings have come from case reports, retrospective examination of laboratory
      values, and analysis of health-care claims databases. This study investigated
      fasting levels of glucose, lipids, and leptin in a non-randomized, cross-
      sectional study of 210 patients, with schizophrenic or schizoaffective disorder,
      treated with a single antipsychotic medication - clozapine, risperidone,
      olanzapine, or a conventional antipsychotic. Glucose tolerance tests (GTT), with
      a 75-g glucose load, were preformed in a subset of patients. In this sample most
      mean fasting glucose and lipid levels were within the normal range and were not
      significantly different across the four drug treatment groups. Patients treated
      with clozapine and olanzapine had higher triglyceride levels than risperidone
      patients. In patients receiving a GTT, risperidone-treated patients had higher
      glucose levels at 1 h than patients treated with olanzapine, and there were more
      patients on risperidone who met American Diabetes Association glucose metabolic
      criteria for diagnosis of diabetes. Although there were no significant
      differences in age or body mass index among the four drug groups, we cannot rule
      out some potential biasing factors we did not assess which could potentially
      influence our results. These include unknown physician preference in drug
      selection based on their beliefs about the weight-inducing or diabetes potential
      of different antipsychotics, differences in visceral fat, and differences in
      patients' antipsychotic drug history.

PMID- 15737249
TI  - Rapid cycling bipolar disorder: biology and pathogenesis.
AB  - The rapid cycling (RC) pattern of a mood disorder is characterized by at least
      four affective episodes (manic, hypomanic or major depressive) during the last
      year; different episodes must be demarcated by a switch to an episode of opposite
      polarity or by a period of remission of at least 2 months. RC is very rare in
      unipolar patients; its prevalence, however, in bipolar patients is 10-30% with
      the majority being women (70-90%). Patients with RC usually suffer from bipolar
      II disorder with onset with a depressive episode. Genetic studies have not
      convincingly shown that the condition is genetically determined. Major
      abnormalities of thyroid function have not been shown to be related to RC, but
      recent studies propose that latent subclinical hypothyroidism might play a role
      in the acceleration of cycles. Perturbations of the circadian biological and
      social rhythms might influence the expression of RC. No major effect of the
      menstrual cycle has been found. Despite the absence of firm empirical data, the
      possible contribution of the kindling phenomenon on the acceleration of cycles
      cannot be excluded. Finally, there is evidence that RC can be induced by the use
      of antidepressant drugs, especially for women.

PMID- 15737250
TI  - Activation of noradrenergic locus coeruleus neurons by clozapine and haloperidol:
      involvement of glutamatergic mechanisms.
AB  - The major brain noradrenergic nucleus locus coeruleus (LC) has long been thought
      to be involved in states of alertness and cognitive processes. These functional
      characteristics make this nucleus interesting with regard to the signs of
      schizophrenia, especially the negative symptoms of the disease. In the present in
      vivo electrophysiological study we analyse a putative interaction between
      endogenous kynurenic acid (KYNA) and the antipsychotic drugs clozapine and
      haloperidol on noradrenergic LC neurons. Previous studies have shown that
      systemically administered antipsychotic drugs increase the neuronal activity of
      LC noradrenaline (NA) neurons. In line with these findings, our results show that
      clozapine (1.25-10 mg/kg i.v.) and haloperidol (0.05-0.08 mg/kg i.v.) increased
      the firing rate of LC NA neurons in anaesthetized rats. Pretreatment with PNU
      156561A (40 mg/kg i.v., 3 h), a potent inhibitor of kynurenine 3-hydroxylase,
      produced a 2-fold increase in rat brain KYNA levels. This treatment prevented the
      increase in firing rate of LC NA neurons induced by haloperidol (0.05-0.08 mg/kg
      i.v.) and clozapine in high doses (2.5-10 mg/kg i.v.). However, the excitatory
      action of the lowest dose of clozapine (1.25 mg/kg i.v.) was not abolished by
      elevated levels of brain KYNA. Furthermore, pretreatment with L-701,324 (4 mg/kg
      i.v.) a selective antagonist at the glycine site of the NMDA receptor prevented
      the excitatory effects of both clozapine and haloperidol. The present results
      suggest that the excitation of LC NA neurons by haloperidol and clozapine
      involves a glutamatergic component.

PMID- 15737253
TI  - Correlation of hallux valgus surgical outcome with AOFAS forefoot score and
      radiological parameters.
AB  - BACKGROUND: The purpose of the study was to evaluate the effect of three
      different types of hallux valgus surgeries on patient function using validated
      questionnaires and to correlate the results with radiographic and physical
      examinations. This study presents the 2-year followup data of a previous
      prospective outcome study. METHODS: One hundred and ninety-six patients were
      enrolled in this study and completed a baseline AAOS Lower Limb Outcomes Data
      Collection Questionnaire. They completed the same form at 6, 12, and 24 months
      after having one of three types of hallux valgus surgeries (106 chevron
      osteotomies, 72 modified McBride procedures, and 18 modified Lapidus procedures).
      This questionnaire included the Short Form-36 Health Survey (SF-36) as well as
      questions relating to lower extremity function. Additionally, physicians were
      asked to complete preoperative and postoperative questionnaires on each patient
      that included radiographic and physical examination data and the type of surgery
      done. Completed outcome surveys and radiographic data were available on 196
      patients, and physical examination scores were available to assign an AOFAS score
      in 111 patients at 24-month followup. A one-way comparison was done after
      stratifying the results for the type of surgery, preoperative hallux valgus angle
      and 1-2 intermetatarsal angle, postoperative hallux valgus angle and 1-2
      intermetatarsal angle, and the change in the angles. RESULTS: Four of the 10 SF
      36 scores (physical function, role-physical, bodily pain, and role-emotional) for
      the combined data improved by more than five points. For the AAOS lower extremity
      function scores, physical health and pain (68.5 to 81.6), satisfaction with
      symptoms (1.8 to 3.6), global foot and ankle (77.6 to 93.4), and shoe comfort
      (29.0 to 58.7) scores all increased significantly. The AOFAS score increased from
      52.6 to 85.5 (p <0.001). Surprisingly, when comparing mild-to-moderate to severe
      deformities preoperatively and postoperatively using the absolute magnitude of
      the angular change in the hallux valgus or intermetatarsal angles, similar
      improvement was noted in AOFAS, SF-36, and AAOS lower extremity scores. The
      magnitude of preoperative deformity, postoperative residual deformity, and
      magnitude of correction also did not significantly change the amount of
      improvement in any of these scores. No significant differences were noted in the
      outcome scores among the three different surgeries. CONCLUSION: Patients who had
      hallux valgus surgery had significant improvements in four of their SF-36 scores,
      four of five of AAOS lower extremity scores, and AOFAS scores. The degree of
      deformity, amount of correction, or type of operation did not influence outcome.

PMID- 15737251
TI  - Effects of quetiapine and haloperidol on body mass index and glycaemic control: a
      long-term, randomized, controlled trial.
AB  - The topic of antipsychotic-induced weight-gain and its relationship to glucose
      metabolism is under-studied. We evaluated the long-term effects of a new
      generation antipsychotic, quetiapine and a conventional antipsychotic,
      haloperidol on body mass index (BMI) and glycaemic control in patients with
      schizophrenia previously treated with conventional antipsychotics. Forty-five
      clinically stable patients with schizophrenia participated in this randomized,
      investigator-blinded, parallel-group comparison of flexible doses of quetiapine
      and haloperidol treatment over 52 wk. Primary outcome measures were change from
      baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no
      between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1)
      and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in
      BMI from baseline for either group. HBA1c levels decreased significantly at end
      point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine
      group (-0.3%, p = 0.5). Although the sample was not generally obese (mean
      baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of
      abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with
      48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19%
      markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values
      decreased from baseline in both the haloperidol and quetiapine treatment groups.
      These findings suggest that switching treatment from a conventional antipsychotic
      to quetiapine is not associated with weight gain or worsening of glycaemic
      control, even in the long term. The study also highlights the high incidence of
      unrecognized glucose dysregulation in patients with schizophrenia receiving
      conventional antipsychotic treatment.

PMID- 15737254
TI  - Health related quality of life, cognitive function, and depression in diabetic
      patients with foot ulcer or amputation. A preliminary study.
AB  - BACKGROUND: Diabetic foot ulcers, foot infection, Charcot foot arthropathy, and
      lower extremity amputation have a severe negative effect on the health-related
      quality of life in individuals with diabetes. The purpose of this study was to
      determine if there is a relationship between these negative effects and cognitive
      impairment or clinical depression. METHODS: Sixty adults with diabetes completed
      the Short Form 36 (SF-36) Health Survey questionnaire, two screening examinations
      for cognitive function (Mini Mental Exam and Clock-Drawing Test), and a screening
      examination for depression (Zung Self-Rating Depression Scale). The two focus
      groups were composed of 20 subjects each who were undergoing treatment for (1)
      diabetic foot ulcers or active Charcot foot arthropathy or (2) lower extremity
      amputation. Twenty diabetic individuals without foot-related morbidity but with
      evidence of peripheral neuropathy as measured by insensitivity to the Semmes
      Weinstein 5.07 (10 gm) monofilament comprised the control group. RESULTS: The SF
      36 Health Survey score was significantly impaired in both the diabetic foot ulcer
      and Charcot arthropathy group (p <0.001) and amputee (p <0.000) group. There was
      no evidence of cognitive impairment or depression in either group. The negative
      impact on health-related quality of life was similar in both focus groups (p
      <0.314). CONCLUSION: The results of this preliminary study suggest that the
      negative impact on health-related quality of life in diabetic patients with foot
      ulcers or Charcot foot arthropathy may be as severe as in similar patients with
      lower extremity amputation. The negative effect did not seem to cause cognitive
      impairment or clinical depression in either focus group.

PMID- 15737255
TI  - Arthrodesis compared to Mayo resection of the first metatarsophalangeal joint in
      total rheumatoid forefoot reconstruction.
AB  - BACKGROUND: Painful forefoot deformity from rheumatoid arthritis can be treated
      with resection of the lesser metatarsal heads combined with either resection or
      arthrodesis of the first metatarsophalangeal (MTP) joint. METHODS: In a
      prospective, randomized study we compared arthrodesis of first MTP joint with
      Mayo resection as part of total forefoot reconstruction in patients with painful
      forefoot deformity from rheumatoid arthritis. The lesser metatarsal heads were
      resected and extensor tenotomy was done in all patients. Thirty-one patients were
      randomized to either the arthrodesis or resection group. RESULTS: After a mean
      followup of 36 (26 to 52) months, the median subjective satisfaction score was 96
      points out of 100 in the resection group and 92 points in the arthrodesis group.
      Significant improvements in pain, handicap, and activity according to Foot
      Function Index (FFI) were found in both groups (p <0.001 except for handicap in
      resection group and activity in fusion group were p=0.02). There were no
      statistically significant differences between the groups in these measures, nor
      in the patients' willingness to have the procedure again. There were no
      recurrences of prominences or tenderness under the forefoot in either group and
      no recurrence of severe hallux valgus in the resection group. The arthrodeses
      healed in 93%. There was no higher risk for clinically relevant IP joint symptoms
      after arthrodesis. The operating time was significantly longer in the arthrodesis
      group but this was not linked to a higher wound infection rate. CONCLUSION: These
      results indicate that Mayo resection may still be a good choice for the first MTP
      joint in total forefoot reconstruction in patients with rheumatoid arthritis.

PMID- 15737256
TI  - Functional outcome of arthrodesis of the first metatarsophalangeal joint using
      parallel screw fixation.
AB  - BACKGROUND: Arthrodesis of the first metatarsophalangeal (MTP) joint is a
      reliable procedure for a painful hallux. Most studies focus on the surgical
      results rather than the functional outcome for the patient. Therefore, we
      examined the effects of first MTP joint arthrodesis on activities of daily living
      and recreational activities. METHODS: Fifty-three patients (60 feet) who had
      isolated arthrodesis of the first (MTP) joint using a parallel screw fixation
      technique were evaluated for the functional outcome after the surgery to
      determine the effect of the arthrodesis on the activities of daily living and on
      recreational sports and exercise. RESULTS: Fusion was achieved in all patients;
      all but three stated that they would have the surgery again. Postoperative pain
      scores evaluated using the Visual Analogue Scale indicated effective pain relief.
      High levels of function were demonstrated in this group of patients. CONCLUSION:
      Arthrodesis of the first MTP joint is not only a successful surgical technique
      for relief of pain and correction of deformity but also allows a high level of
      function in everyday life and in recreational activities.

PMID- 15737257
TI  - Morbidity associated with anterior iliac crest bone grafting in foot and ankle
      surgery.
AB  - BACKGROUND: Substitutes for bone graft have been advocated to avoid the potential
      morbidity associated with harvest of autogenous iliac crest graft. However, no
      current commercially available graft equals autogenous bone's osteoinductive and
      osteoconductive qualities. We reviewed our patients' morbidity after harvest of
      anterior iliac crest bone grafts for procedures involving the foot and ankle.
      METHODS: A computerized analysis of patient records was undertaken to identify
      all patients who had a harvest of unicortical iliac crest bone graft during a 12
      year period. Patients were contacted either by telephone or by mailed
      questionnaire, inquiring about the postoperative morbidity of the procedure.
      Medical records were reviewed for any related complications. RESULTS: Of the 169
      patients identified, 134 could be contacted. Follow-up ranged from 1 to 13 years.
      Not all patients answered every question. At latest follow up, 120 (90%)-patients
      reported no pain at the bone graft site. Eleven patients complained of persistent
      residual numbness lateral to the harvest site on the pelvis. Of these 120
      patients, 32 (27%) reported that pain at the graft site was greater than the pain
      at the operative site during the initial postoperative period. No patients had
      extra hospital days as a result of the bone graft harvest. No deep infections
      occurred, although 12 (6.7%) of 180 patients had a postoperative hematoma or
      seroma. Overall, 116 (90%) of 129 patients were satisfied or very satisfied with
      their bone graft harvest. CONCLUSIONS: Harvesting of autogenous iliac crest bone
      graft provides the optimal bone graft material, yields minimal morbidity, and is
      an acceptable choice in supplementing surgical procedures on the foot and ankle.

PMID- 15737258
TI  - Proximal crescentic metatarsal osteotomy: the effect of saw blade orientation on
      first ray elevation.
AB  - BACKGROUND: Moderate and severe hallux valgus deformities generally require a
      proximal metatarsal osteotomy to correct a widened intermetatarsal angle.
      Although excellent results have been reported using the proximal crescentic
      osteotomy, concerns have been raised about the incidence of postoperative dorsal
      malunion, which may lead to transfer lesions. The objectives of this paper were
      to evaluate the influence of saw blade angulation on the final position of the
      first metatarsal and to test a new technique used to ensure proper orientation of
      the osteotomy. METHODS: For part I of the study, 26 Sawbones specimens with
      hallux valgus deformities were corrected using a proximal crescentic osteotomy
      with the saw blade position incrementally rotated in the coronal plane. The
      sagittal change in the final position of the metatarsal was quantified
      radiographically and correlated to the saw blade orientation. For part II of the
      study, a Kirschner wire was placed in a vertical position into the medial
      cuneiform to serve as a guide for the crescentic saw blade in 13 cadaver feet
      with hallux valgus. Metatarsus primus elevatus was measured after surgical
      correction. RESULTS: Part I of the study demonstrated a highly linear
      relationship (R2=0.95) between first metatarsal elevation and the orientation of
      the saw blade. Every 10-degree of saw blade angulation resulted in a 2-mm change
      in the sagittal position of the first metatarsal. In part II of the study, the
      average change in metatarsus primus elevation for the 13 specimens after surgical
      correction of the hallux valgus deformity was only 1.1 mm (range -3.9 to +4.9
      mm). Eleven of the 13 specimens had less than 2.5 mm of elevatus. CONCLUSION:
      Dorsal malunion of the first metatarsal after proximal crescentic osteotomy is a
      recognized complication. The final position of the hallux metatarsal is
      influenced by the coronal plane orientation of the saw. A new technique is
      described to aid the surgeon in proper alignment of the saw and help prevent
      excessive first ray elevation.

PMID- 15737259
TI  - Plantar pressure and load in cadaver feet after a Weil or chevron osteotomy.
AB  - BACKGROUND: Since metatarsal osteotomy was first used to treat metatarsalgia in
      the early twentieth century, many techniques have been described to accomplish
      the basic aim of reduction of load transmission through the operated metatarsal
      and reduction of localized high pressure on the plantar surface of the
      metatarsal. Our study examined two popular distal metatarsal neck osteotomies
      used for the relief of central metatarsalgia and the biomechanical changes that
      result from their use in a cadaver forefoot model. METHODS: After applying 445 N
      (100 lbs) of axially directed force, we measured plantar pressure using the
      TekScan HR Mat (TekScan, Inc., South Boston, MA) in twelve paired, thawed, fresh
      frozen intact cadaver legs, then after either a Weil or chevron osteotomy of the
      second metatarsal and finally after the addition of the same osteotomy of the
      third metatarsal. RESULTS: Load in the forefoot was not significantly affected by
      the Weil osteotomy. A significant increase in load was produced in the first
      metatarsal region, and significant decreases in load were produced beneath the
      operated metatarsal heads after the chevron osteotomy. Average pressure in the
      contact area of the forefoot showed similar trends; however, load and pressure
      changes occurred independently, owing to the changes in contact area produced by
      the osteotomies. No significant changes were observed in the nonoperated
      metatarsal regions. CONCLUSIONS: In this model, the chevron osteotomy more
      effectively reduced load and plantar pressure in the operated metatarsal regions;
      however, increases in load and pressure were observed in the first metatarsal
      region. The increase in pressure without a change in load in region 3 (third
      metatarsal) after a Weil osteotomy of the third metatarsal was attributed to the
      creation of a plantar prominence. This study did not show a reduction in load
      transmission as a result of the Weil osteotomy, which contradicts the proposed
      mechanism of clinical benefit. An intact first ray likely prevents transfer of
      load or pressure to adjacent lesser metatarsals with chevron osteotomy.

PMID- 15737260
TI  - Calcaneal lengthening: investigation of deformity correction in a cadaver
      flatfoot model.
AB  - BACKGROUND: Evans showed that lengthening the lateral column by inserting
      structural bone graft into the anterior calcaneus could correct abduction and
      valgus deformity in flatfoot. To better understand the mechanism of correction
      and the three-dimensional effect of this procedure a cadaver study was done.
      METHODS: Three cadaver flatfoot models were used. Computed tomographic (CT) scans
      were made of each specimen before and after lengthening. Data from these scans
      were used to determine the center of volume of the talus, navicular, cuboid, and
      calcaneus. The angular and translational motions for each bone were determined.
      RESULTS: On average, relative to the talus, the navicular moved 18.6 degrees of
      rotation in adduction, 2.6 degrees of rotation in pronation, and 3.4 degrees in
      plantarflexion. The average translation was 5.6 mm medial, 0.4 mm posterior, and
      1.8 mm plantar. The cuboid moved an average of 24.2 degrees of rotation in
      adduction and lengthening, 13.9 degrees in pronation, and 1.9 degrees in
      plantarflexion. The average translation was 9.4 mm medial, 2.6 mm distal, and 1.5
      mm plantar. The calcaneus moved an average of 4.4 degrees of rotation in
      adduction, 0.1 degrees of rotation in eversion, and 1.3 degrees of
      plantarflexion. The average translation was 3 mm medial and 0.7 mm posterior with
      no plantar translation. CONCLUSIONS: The mechanism of Evans calcaneal lengthening
      involves adduction and plantarflexion of the midfoot relative to the hindfoot.
      The cuboid and navicular appear to move as a unit. The shape of the talar head,
      axis of the subtalar joint, degree of initial deformity, competence of plantar
      soft tissues, such as the long plantar ligament, and adequate length of the
      Achilles tendon are important. Knowing what qualitative three-dimensional changes
      take place allows a better understanding of the mechanics of the procedure and
      its possible applications.

PMID- 15737261
TI  - Efficacy of plantar loading parameters during gait in terms of reliability,
      variability, effect of gender and relationship between contact area and plantar
      pressure.
AB  - BACKGROUND: The purpose of this study was to determine plantar pressure and
      contact areas of the foot inside the athletic shoe during activity. The
      objectives were to determine if plantar pressure and contact area measurements
      collected on multiple trials from the same subject were reliable, to determine
      the variability of measurements between subjects as compared to that found
      between steps within a single subject, to determine the relationship between
      contact area and plantar pressure, and to ascertain whether there were any
      systematic gender differences in these measurements. METHODS: Sixteen healthy
      adults volunteered for participation in the first part of the study that was
      designed to determine reliability and variability of the testing methodology. A
      separate group of fifty healthy high school and collegiate athletes participating
      in soccer, field hockey, basketball, and lacrosse comprised the second part of
      the study that was designed to investigate gender differences in terms of
      normalized midfoot plantar pressure and contact area, and the interrelationship
      between the two measurements. Data were collected during the midstance phase of
      gait, using the Pedar in-shoe measurement system (Novel GMBH, St. Paul, MN).
      Athletes wore their own athletic shoes and performed walking trials on a surface
      similar to that used in their sport. The foot was divided into four regions based
      on radiographic measurements. RESULTS: The midfoot region demonstrated excellent
      reliability across multiple trials of the same subject in contact area and
      plantar pressure, and the variability between steps within a single subject was
      small when compared to that between subjects. Normalized midfoot contact area and
      plantar pressure values were highly correlated with r values of 0.862 on the left
      foot and .912 on the right foot. No significant differences were found in
      normalized midfoot contact area or plantar pressure values between males and
      females. CONCLUSIONS: The Pedar in-shoe pressure measurement system can be used
      reliably to quantify contact area and plantar pressure beneath the midfoot region
      during the midstance phase of gait. This measurement technique can now be used in
      risk factor studies designed to identify individuals at risk for injury to the
      foot, ankle, and other lower extremity structures.

PMID- 15737262
TI  - The medial longitudinal arch as a possible risk factor for ankle sprains: a
      prospective study in 83 female infantry recruits.
AB  - BACKGROUND: Ankle sprains are frequent, especially in athletes, soldiers, or
      others who perform high levels of physical activity. Although prevention is a
      primary goal, little is known about the risk factors. We evaluated the
      association of the structure of the medial arch of the foot to the occurrence of
      acute and recurrent ankle sprains in 83 female infantry recruits. We found no
      previous studies on ankle sprains in women in the English literature. METHODS:
      Arch height was quantified using the Chippaux-Smirak index, and each arch was
      classified as high, normal, or low. Retrospective data were obtained from
      questionnaires in which the soldiers noted whether or not they had had ankle
      sprains in the past, the grade of the sprain, and recurrence. Prospective data
      were accumulated in the 4 months of basic training, during which time every ankle
      sprain was documented and classified according to its grade and cause. RESULTS:
      The retrospective data showed more frequent ankle sprains in the low arch group
      than in the normal arch group, mainly in the right foot (RR of 2.9, p <0.05).
      Recurrent sprains studied retrospectively also showed that more sprains occurred
      in the low arch group than in the normal arch and high arch groups (RR of 10.3, p
      <0.05). The prospective data suggested a pattern toward the same outcome (50% in
      the low arch as opposed to 36% in the normal arch group, RR, 1.3), but with no
      statistical significance. CONCLUSIONS: We concluded that a low arch of the foot
      might be a risk factor for ankle sprains. However, our study consisted of a
      relatively small population, and further studies are needed.

PMID- 15737263
TI  - Posterior tibial tendon dysfunction secondary to os subtibiale impingement: a
      case report.

PMID- 15737264
TI  - The crossed-leg test for examination of ankle syndesmosis injuries.

PMID- 15737265
TI  - [The introduction and development of the new programme of family and community
      medicine. A new opportunity].

PMID- 15737266
TI  - [Self-auditing as an instrument of educational assessment].

PMID- 15737267
TI  - [Results of a benchmarking exercise for primary care teams in Barcelona, Spain].
AB  - OBJECTIVE: To identify primary care teams (PCT) with the best overall performance
      and compare these with other PCT with benchmarking methods. DESIGN: Descriptive,
      cross-sectional study of a set of indictors for the year 2002. SETTING: City of
      Barcelona (northeastern Spain). PARTICIPANTS: Thirteen seven PCT with more than 2
      years' experience, and 771,811 inhabitants in the catchment area. MAIN MEASURES:
      Indicators were chosen from among those proposed by an advisory group, depending
      on feasibility of obtaining information. A total of 17 indicators in 4 dimensions
      were studied: accessibility, clinical effectiveness, case management capacity,
      and cost-efficiency. Each PCT was scored for each indicator based on the
      percentile group in the distribution of scores, and for each dimension based on
      the mean score for all indicators in a given dimension. Overall score for PCT
      performance was calculated as the weighted sum of the scores for each dimension.
      As descriptive variables we analyzed time operating under the revised
      administrative system, patient visits per population served, the population's
      economic capacity and age of the population. RESULTS. Nine PCT were identified as
      the benchmark group. Teams in this group had been operating under the revised
      administrative system for significantly longer than other PCT. In comparison to
      other PCT, the benchmark group obtained higher scores on all four dimensions,
      better results on 14 separate indicators, the same results for 1 indicator, and
      worse results for 2 indicators. CONCLUSIONS. Benchmarking made it possible to
      identify PCT with the best performance, and to identify areas in need of
      improvement. This approach is a potentially useful tool for self-evaluation and
      for stimulating a dynamic for improvement in primary care providers.

PMID- 15737268
TI  - [Benchmarking in organizations].

PMID- 15737269
TI  - [Consensus on a process of benchmarking in primary care in Barcelona].
AB  - OBJECTIVE: To define the strategy, the conceptual framework, the methodology and
      the indicators that are needed to promote and consolidate the culture of external
      reference (benchmarking) as a strategy for change in Primary Care teams (PCT).
      DESIGN: Cross-sectional, descriptive study. SETTING: Primary care services of the
      Barcelona City Health Region. METHOD: Two stages were distinguished. At the first
      stage, an adviser group was set up. This was divided into 4 focus groups in which
      the main lines, the conceptual framework, the sizes, the indicators and the
      methodology for comparing PCTs were agreed. The second stage, that of
      prioritization, was conducted by means of a questionnaire to opinion-formers. For
      each of the indicators proposed, they appraised the degree of agreement, the
      suitability and relevance of indicators, the capacity of PC to modify results and
      the practicality of the information for composing the indicators. RESULTS: The
      involvement of professionals, their approach to improvement, and the transparency
      and dissemination of the evaluation were identified as strategic elements of
      benchmarking dynamics. In line with the basic principles of PC and the health
      system, 6 dimensions for evaluation were set: accessibility, effectiveness,
      capacity to resolve problems, longitudinality, cost-efficiency, and results. 43
      of the 57 indicators prioritized gained the consensus of over 90% of the
      consultants. CONCLUSIONS: Evaluation as a useful tool for managing PC quality has
      to generate improvements or changes in PCTs. The involvement of professionals in
      the design and development of evaluation may help both its acceptance and the
      implementation of the changes arising from it. The indicators used and the effect
      of benchmarking policy on the results of PC service delivery require evaluation.

PMID- 15737270
TI  - [Is breast-feeding a protective factor for infectious diseases? A case-control
      study].
AB  - AIM: To analyze if breast-feeding (BF) is a protective factor against infectious
      diseases. DESIGN: Case-control study. Retrospective study during 1998. SETTING:
      Primary care. Teaching health center. Population of 22,500 inhabitants. PATIENTS:
      We consider an alpha risk of .05 and a beta risk of .20, unilateral hypothesis.
      We estimated a sample of 48 children in the "case" group and 144 in the "control"
      group. Random sample. MEASURES: Cases were children with 3 or more acute
      respiratory or digestive infectious episodes during the first year of age.
      Controls were children with less than 3 episodes. We analyze exposure to breast
      feeding (BF) and we consider it if the child had at least 3 months of BF. In
      other case we define as a non-exposure child. We have calculated odds ratio (OR)
      and its 95% confidence intervals. RESULTS: 60.4% of the children were BF after
      birth. But only 28.5% lasted 3 months, and only 13.9% lasted 1 year. The median
      of BF was 3.3 months (SD 4.2). 79.2% of the children have a respiratory
      infectious disease in the first year and 14.6% diarrhea. In children less than 1
      year old the OR was 0.81 (95% CI, 0.40-1.63). In the period 3-6 months old we
      have found an OR of 0.346 (95% CI 0.161-0.744). CONCLUSIONS: In children aged
      less than 1 year, we have not found protective effects of breast-feeding against
      acute respiratory infectious diseases. Only in the period 3-6 months old, we have
      found that BF protects against these diseases.

PMID- 15737271
TI  - [Evaluation of referrals in primary care].
AB  - OBJECTIVE: To study the process of referral from primary care in a health area in
      Madrid. The second objective was to evaluate the trends in the referral process.
      DESIGN: Observational, descriptive and cross-sectional study. SETTING: Three
      urban health centers in the Area 2. PARTICIPANTS: All referrals made by 13
      doctors during 3 consecutive weeks. The total number of visits attended were
      6012. The study was realized between February 2002 and January 2003. MAIN
      MEASUREMENTS: Patient, doctor and referral characteristics on every referral.
      RESULTS: 349 referrals were studied. The rate of referral 5.8% (5.21-6.39). The
      referred patients, 65.5% women, medium age 50.6+/-21. The specialties that
      received more referrals are gynecologist, ophthalmology, dermatology,
      otorhinolaryngology, rehabilitation, orthopedic surgeon and general surgeon. The
      most common conditions referred, 25.6% of all referrals, are gynecologist check,
      blindness, other illnesses of subcutaneous cellular tissue, arthrosis, joint
      pain, diabetes, benign neoplasm of skin, depression and hypoacusis. 92.3% of the
      referrals were sent to the specialist center. 89.7% were normal (no urgent). The
      reason for referral was to accede to the patient's request in 18.3% of the
      referrals. CONCLUSIONS: The process of referral is similar to previous studies.
      Although people are more participative, have more information and the defensive
      medicine is increasing, the process of referral have not changed.

PMID- 15737272
TI  - [The increase in prescription of anti-depressants].

PMID- 15737273
TI  - [Observational studies to evaluate the clinical effectiveness of drugs. Use of
      guide lists for their design, analysis, and interpretation].

PMID- 15737274
TI  - [Prevalence of treated hypothyroidism in the adult population].

PMID- 15737275
TI  - [Vaccination of immigrant children: how do they reach our clinics?].

PMID- 15737276
TI  - [Depression in primary care: what is its pharmacological cost?].

PMID- 15737277
TI  - [Study in primary care on the adherence of young children with acute pathology to
      their antibiotic treatment].

PMID- 15737278
TI  - [Consumption of antibiotics and resistance to bacteria].

PMID- 15737279
TI  - [What occurs within companies. Should we speak out?].

PMID- 15737280
TI  - [Prevention of tuberculosis in Spain during XXIst century].

PMID- 15737281
TI  - [Neonatal respiratory failure associated with mutation in the surfactant protein
      C gene].
AB  - Respiratory insufficiency in a term infant during the first weeks of life is
      unusual. Possible causes include interstitial or diffuse lung disease, which are
      a heterogeneous group of mostly idiopathic disorders, characterized by diffuse
      infiltrates, restrictive functional defect, and disordered gas exchange. A form
      of interstitial lung disease that can affect infants, children or young adults is
      that associated with congenital surfactant protein B or C deficiency, in which
      the inflammatory process leading to interstitial fibrosis is preceded by the
      accumulation of proteinaceous material in the alveolar space. We assessed the
      role of potential abnormalities in the surfactant proteins B and C in a Spanish
      family in which two infants showed progressive neonatal respiratory failure
      associated with radiological and pathological alterations compatible with
      interstitial lung disease. The father had a history of respiratory disease since
      childhood. The two affected children in this family had abnormal expression of
      surfactant C precursor protein, with markedly decreased levels of the mature
      protein. Moreover, a previously unreported mutation in the gene encoding
      surfactant protein C, which was found in this family, is described.

PMID- 15737282
TI  - [Tuberculous meningitis: a review of 27 years].
AB  - OBJECTIVES: To analyze the features and outcome of children with tuberculous
      meningitis (TM) in a tertiary hospital in Madrid, with special emphasis on the
      possible influence of HIV infection, immigration and withdrawal of the Bacille
      Calmette-Guerin (BCG) vaccine in Madrid in 1987. METHODS: We reviewed the medical
      records of patients with TM diagnosed over a 27-year period (1977-2003). TM was
      diagnosed on the basis of compatible cytochemical findings in cerebrospinal fluid
      (CSF), plus a) isolation of Mycobacterium tuberculosis in CSF or gastric fluid;
      b) positive Mantoux test, or c) previous contact with active tuberculosis.
      RESULTS: Twenty-eight cases of TM were diagnosed. There were 24 cases (85 %) in
      the first 14 years versus only four cases (15 %) in the last 13 years. None of
      the children was co-infected with HIV. The median age was 3 years and 4 months.
      Only two of these had received the BCG vaccine. The source of infection was
      identified in 64 %. At admission, 57 % had nuchal rigidity, 46 % had neurological
      focality, and 54 % had an abnormal chest roentgenogram. The Mantoux purified
      protein derivative (PPD) test was positive in 89 % at diagnosis. Zhiel-Nielsen
      smear in CSF was positive in 3.5 %, and a positive culture from CSF was obtained
      in 32 %. Computed tomography scan was performed in 22 children and showed
      hydrocephalus in 90 %. All patients were treated with four drugs, with no
      significant adverse events. Corticoids (89 %), ventricular-peritoneal shunt (43
      %) and antiepileptic drugs (39 %) were widely used as complementary treatments.
      Mortality was 12 %. Half of the patients had sequels, which were mostly
      permanent. The most frequent and severe complication was neurodevelopmental delay
      (21 %). Severe sequels occurred in children with more advanced stages of illness.
      CONCLUSIONS: The frequency of TM has decreased in the last 15 years, despite the
      emergence of HIV and immigration from countries where tuberculosis is endemic.
      These data are in agreement with the general reduction of the incidence of TM in
      our environment. Withdrawal of the BCG vaccine in Madrid in 1987 did not increase
      cases of TM in our hospital; on the contrary, these have decreased. A
      considerable percentage of children with advanced stages of TM show severe
      sequels.

PMID- 15737283
TI  - [Evaluation of twenty-three episodes of acute thoracic syndrome in patients with
      sickle cell anemia].
AB  - INTRODUCTION: Acute thoracic syndrome (pneumonia and/or lung infarction) is a
      significant cause of morbidity and mortality in sickle cell anemia. OBJECTIVE: To
      review the clinical manifestations, management and outcome of episodes of acute
      thoracic syndrome in our hospital. METHODS: We performed a retrospective review
      of all the episodes of acute thoracic syndrome diagnosed at our center in
      patients younger than 18 years of age with sickle cell anemia. Clinical,
      laboratory and radiological findings, outcome and treatment were analyzed. Data
      from patients < 3 years and > 3 years of age were compared (Fisher's exact test
      and the Mann-Whitney U test). RESULTS: Twenty-three episodes of acute thoracic
      syndrome were evaluated in eight out of 12 patients with sickle cell anemia
      followed-up in our hospital. These episodes represented 36 % of the total time of
      admission in these patients. The most frequent cause was infection. The most
      frequent symptoms were fever (87 %), cough (61 %) and cold (35 %) symptoms.
      Seventy-four percent of the patients were not diagnosed at admission, either
      because the chest X-ray was normal (52 %) or because it was not performed (22 %)
      due to the absence of pulmonary manifestations. Patients aged more than 3 years
      old had more severe episodes, with greater clinical compromise and radiological
      involvement and increased use of analgesia. Transfusions were administered in 65
      % of the episodes and in five patients (> 3 years) a partial exchange transfusion
      was performed. In five patients corticoid treatment was associated with febrile
      relapses. CONCLUSIONS: Acute thoracic syndrome is frequent in sickle cell disease
      and is more severe in children older than 3 years. Its diagnosis requires a high
      index of suspicion, due to multiple forms of clinical presentations and normal
      chest radiology at admission.

PMID- 15737284
TI  - [Time trends and geographical variations in the prevalence of symptoms of
      allergic rhinitis in 6-7-year-old children from eight areas of Spain according to
      the ISAAC].
AB  - BACKGROUND: Phase III of the International Study of Asthma and other Allergies in
      Childhood (ISAAC) was carried out in schoolchildren aged 6-7 years from eight
      areas of Spain to estimate time trends and geographic variations in the
      prevalence of symptoms of allergic rhinitis (AR). MATERIAL AND METHOD: A standard
      and validated questionnaire was used following ISAAC methodology and was
      completed by the schoolchildren's parents. The prevalence of symptoms of AR in
      Phase I (1993-1994) and Phase III (2001-2002) was compared. Eight centers
      participated: Asturias, Barcelona, Bilbao, Cartagena, Castellon, Madrid, Pamplona
      and Valencia. Poisson regression was used in the analysis. RESULTS: A total of
      25,113 schoolchildren were studied with a median participation of 81.7 %. In all
      centers, AR symptoms tended to increase, with a prevalence ratio of
      rhinoconjunctivitis in the previous year of 1.61 (95 % confidence interval: 1.48
      1.76) when both phases, adjusted by gender, center, and seasonal variation, were
      compared. The prevalence of AR symptoms was higher in boys than in girls. Wide
      variations in the prevalence of AR were observed across centers with a higher
      prevalence in Asturias, Madrid, Cartagena and Bilbao. Lower prevalences were
      reported in Barcelona, Castellon and Pamplona. CONCLUSIONS: There seems to have
      been a general increase in AR symptoms. Substantial variations between centers
      suggested that there may be local differences in risk factors. Intense research
      will be required for satisfactory preventive actions.

PMID- 15737285
TI  - [Consistency of clinical practice with the scientific evidence in the management
      of childhood asthma].
AB  - INTRODUCTION: There is substantial inconsistency between the evidence available
      on the management of childhood asthma and its application in practice. OBJECTIVE:
      To evaluate the degree of appropriateness of current management of childhood
      asthma. MATERIAL AND METHODS: We performed a structured review of the articles
      published on appropriateness in the recent biomedical literature (last 5 years).
      Methodological analysis and qualitative synthesis were performed. RESULTS: Twenty
      three articles were identified that reflected the following problems:
      insufficient documentation on trigger factors, evolution of pulmonary function
      and symptoms, inadequate guidelines on the treatment of exacerbations, inadequate
      use of inhaler devices, insufficient use of anti-inflammatory drugs, unjustified
      heterogeneity in the selection of anti-inflammatory drugs, lack of correlation
      between severity and level of treatment, lack of written guidelines on customized
      self-management, unjustified use of antibiotics, and lack of pulmonary function
      testing devices. CONCLUSIONS: The management of childhood asthma should be
      reviewed since a large number of decisions made in clinical practice are not
      always based on valid scientific evidence.

PMID- 15737286
TI  - [Burnout syndrome among health workers in pediatrics].
AB  - BACKGROUND: Burnout syndrome (BS) is a chronic adaptation disorder that provokes
      serious problems in occupational behavior. OBJECTIVE: In the present study we
      assessed the prevalence of burnout syndrome in pediatric healthcare workers.
      DESIGN: Cross-sectional, descriptive study. MATERIAL AND METHODS: In November
      2002, the Maslach Burnout Inventory was given to 127 staff members (doctors,
      nurses and nurse assistants) working in a pediatrics department. The
      questionnaire includes 22 items that explore three aspects of BS: a) emotional
      exhaustion; b) depersonalization, and c) personal achievement. RESULTS: The
      questionnaire was completed by 93 staff members (73.2 % of the whole sample; 83 %
      women and 17 % men). The mean age was 38.6 +/- 10.2 years and the median number
      of years worked was 10 (range: 1-37 years). Twenty-nine percent were
      pediatricians, 50.5 % were nurses and 20.5 % were nurse assistants. A total of
      20.8 % had a high level of BS, 19.8 % had a moderate level and 59.4 % showed a
      low level. When sub-scales were applied, the results showed that 67.7 % of
      respondents presented a low level of personal achievement, 14.5 % had high scores
      of emotional exhaustion and 23.9 % obtained high scores in the depersonalization
      scale. CONCLUSIONS: BS is present in a significant percentage of hospital workers
      attending pediatric patients. In our sample, the most notable component of BS was
      the lack of personal achievement. This finding alerted us to the eventual
      presence of negative attitudes toward self and professional activity, as well as
      to the loss of interest in pediatric care, low productivity and diminished self
      esteem. We believe that specific strategies should be implemented to attenuate
      the factors influencing the development of BS in pediatric health staff.

PMID- 15737287
TI  - [Activity of a short-stay observation unit in an emergency department of a
      tertiary hospital. A two-year experience].
AB  - OBJECTIVES: To describe the characteristics of the activity of a short stay
      observation unit (SSOU) in a tertiary hospital, and to analyze its influence on
      the hospitalization rate. MATERIAL AND METHODS: The activity of the SSOU during
      the first 2 years after opening is described. Descriptive variables were
      registered. Hospitalization activity during the first 5 months after opening the
      unit was compared with the activity during the same period in the previous year.
      RESULTS: From June 1, 2001 to May 31, 2003, 74,989 patients were admitted to the
      emergency department (ED) and 2,438 (3.25 %) were transferred to the SSOU. The
      mean age of the patients was 64.55 months. The mean length of stay was 5 hours
      and 50 minutes. The main discharge diagnoses were gastrointestinal disease (30.2
      %), accidents (15 %), respiratory illness (12.5 %) and febrile syndrome (9.8 %).
      The hospitalization rate in patients admitted to the ED was 5.8 % from June 1,
      2000 to October 1, 2000 and was 4.28 % in the same period in 2001. The mean
      diagnosis-related group (DRG)-weight was 0.8648 in 2000 and was 0.9078 in 2001.
      Total weight was 680.66 in 2000 and 495.69 in 2001, allowing an approximate
      saving of 329,162 Euros. CONCLUSIONS: The opening of the SSOU has been useful in
      the assessment and treatment of common childhood diseases and has helped reduce
      the hospitalization rate, increase the complexity of inpatients and lower costs.

PMID- 15737288
TI  - [Black stain: a common problem in pediatrics].
AB  - BACKGROUND: Black stain is a common discoloration in pediatric patients. It is
      caused by microorganisms present in the saliva and is characterized by
      distinctive dark dots localized at the tooth surface parallel to the gingiva,
      both in deciduous and permanent dentition. OBJECTIVE: To determine the prevalence
      of black stain in a group of children in Valencia, Spain and its relationship
      with dental caries. MATERIAL AND METHODS: A total of 1,100 children aged between
      4 and 11 years old were examined by a single observer between January and June
      2003. RESULTS: The prevalence of black stain varied in the children studied.
      CONCLUSIONS: The prevalence of black stain was 7.54 % in our study. No
      differences were found between sexes or between anterior and posterior teeth.
      Treatment of black stain consists of professional cleaning every couple of months
      since the discoloration frequently tends to reappear.

PMID- 15737290
TI  - [Pulse oximetry in neonatal care in 2005. A comprehensive state of the art
      review].

PMID- 15737289
TI  - [Prevalence of oral habits and teeth alterations in schoolchildren from Valencia
      (Spain)].
AB  - INTRODUCTION: Oral habits are acquired through the repetition of actions that
      serve to calm an emotional need of the child. All these oral habits can change
      the position of the teeth and arches. Pediatricians should identify these habits
      to instigate successful treatment. OBJECTIVE: The aim of the present study was to
      determine the prevalence of oral habits in 1,100 Valencian schoolchildren and
      identify the dental alterations associated with these habits. MATERIAL AND
      METHODS: Between January and June 2003, 1,100 children aged between 4 and 11
      years old were examined by two observers, a dentist and a pediatrician, who were
      specially trained to detect anomalous habits. RESULTS: The prevalence of each of
      the distinct habits studied varied. CONCLUSIONS: The conclusions of our study
      were: a) the prevalence of oral habits was 53 %; b) no differences in oral habits
      were found between boys and girls, and c) open bite, maxillary cross-bite and
      overjet can be related to oral habits, although this association was not
      statistically significant.

PMID- 15737291
TI  - [Usefulness of chemotherapy associated with surgery in the management of
      nontuberculous mycobacterial adenitis].
AB  - BACKGROUND: In recent years, lymphadenitis caused by atypical mycobacteria (also
      called nontuberculous mycobacteria [NTMB] or, more recently, environmental) have
      played a significant role in the differential diagnosis of adenitis in non
      immunocompromised children. OBJECTIVES: To describe the clinical and pathological
      findings in childhood NTMB adenitis and study the possible usefulness of
      antimicrobial therapy in addition to surgery. METHODS: We present eight cases of
      neck lymphadenitis occurring over a 5-year period. All of the children received
      combined chemotherapy, and six also underwent surgery. Of the two remaining
      patients, the parents of one child refused surgery and a watchful approach was
      adopted in the other. RESULTS: Complete clinical recovery was achieved in all
      patients except one who did not undergo surgery. CONCLUSIONS: Prolonged
      administration of two antibiotics (of which one must be clarithromycin) in
      addition to surgery was well-tolerated and could be useful in patients with NTMB
      neck lymphadenitis.

PMID- 15737293
TI  - [Contact dermatitis due to temporary henna tattoos].

PMID- 15737294
TI  - [Arrhythmogenic cardiomyopathy or fatty replacement of the right ventricular
      myocardium? Report of two cases].

PMID- 15737292
TI  - [Juvenile amyopathic dermatomyositis and calcinosis].
AB  - Juvenile dermatomyositis (JDM) is a chronic multisystemic disease. It is believed
      to be of autoimmune etiology and is characterized by the presence of vasculitis
      affecting striated muscle and skin. Clinical description consists of general
      symptoms (anorexia, weight loss, asthenia, fever), typical manifestations
      (muscular and cutaneous) and possible systemic alterations. We report the case of
      a 5-year-old boy diagnosed with JDM who presented difficulty in walking,
      inability to completely extend the right lower extremity and calcinosis 12 months
      after the development of incorrectly evaluated cutaneous alterations. We aim to
      highlight the importance of early diagnosis and treatment of this illness. Since
      the introduction of corticosteroid therapy, prognosis has improved but functional
      outcome still depends on the presence of calcinosis and muscular contractures.

PMID- 15737295
TI  - [False-positive results for hyperglycemia with rapid tests used in Neonatology
      Units].

PMID- 15737296
TI  - [Appendicitis in infants. A sometimes difficult diagnosis].

PMID- 15737297
TI  - [Choice of oral corticosteroids for asthma exacerbations].

PMID- 15737298
TI  - [Pain and tumefaction of the hands and feet in a 9-month old infant].

PMID- 15737299
TI  - [Cost-effectiveness of an intervention based on the Global INitiative for Asthma
      (GINA) recommendations using a computerized clinical decision support system: a
      physicians randomized trial].
AB  - BACKGROUND AND OBJECTIVE: To assess the cost-effectiveness of an intervention
      based on the Global INitiative for Asthma (GINA) recommendations as compared to
      usual care. SUBJECTS AND METHOD: Pragmatic, cluster-randomised trial. Ten
      pneumologists and 10 general practitioners were randomised to an intervention or
      control group, recruiting 98 and 100 asthma patients, respectively. The
      intervention consisted of an education program and a clinical decision support
      system (CDSS) providing recommendations based on the GINA. The control group was
      characterized by usual care. Effectiveness was assessed by the health related
      quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ).
      Costs were computed from the resource consumption recorded during a 12 months
      follow-up period, and the cost-effectiveness of the intervention was investigated
      in an incremental analysis. RESULTS: The intervention effect on the SGRQ total
      score was estimated as a 6.8 point reduction (95% confidence interval, 2.5-11.1;
      p = 0.0021), and a significant improvement in the SGRQ subscores and in the
      symptoms-free periods were also observed. From the social perspective, the mean
      total costs showed savings of -1,022 Euros (95% confidence interval, -2,165 to
      122; p = 0.0795) in intervention group as compared to usual care. The incremental
      analysis confirmed that the intervention was cost-effective. CONCLUSIONS: The
      implementation of an asthma management program based in GINA recommendations
      improved the patient's health related quality of life and was cost-effective as
      compared to usual care.

PMID- 15737300
TI  - [Elderly patients with recurrent falls. Role of posturographic studies].
AB  - BACKGROUND AND OBJECTIVE: Our purpose was to provide information about static and
      dynamic balance posturographic disorders in elderly people with recurrent falls,
      and to compare the results with a healthy elderly group. PATIENTS AND METHOD: We
      included 95 subjects: 57 patients who fell (86% women; age, 78.1 years) and 38
      controls. Posturography by Balance Master (Neurocom). Tests performed included:
      a) weight bearing squat (WBS); b) modified clinical test for the sensory
      interaction on balance (MCT); c) sit to stand (SS); d) walk across (WA), and e)
      step and over (SO). RESULTS: No differences in the WBS test between both groups.
      MCT test: The speed of the movement of the gravity center standing on a firm
      surface was faster in the fallers group, both with open (p = 0.034) and closed
      eyes (p = 0.003). The same was seen when we assessed the balance on a foam
      surface (p < 0.005). 45% of subjects with falls showed instability and fell when
      they tried to stand if we altered propioceptive conditions and nullified visual
      afference, as compared to only 18.4% of the control group (p = 0.009). SS test:
      The elapsed time (in seconds) in order to stand was greater in the study group.
      d) WA test: Walking velocity was faster in the fallers group. SO test: Non
      fallers made more body pressure when they went down a step, without interaction
      with age or gender. CONCLUSIONS: There was an increase in the number of
      individuals in the fallers group who fell after nullifying visual and
      propioceptive afferences. It seems necessary to identify these patients in order
      to establish early intervention programs. The abnormal results in tests which
      assess daily life activities could be associated with an after-fall anxiety
      syndrome. Posturography could be a good way to detect the after-fall anxiety
      syndrome and to develop effective strategies for prevention and treatment.

PMID- 15737301
TI  - [IL4RA gene polymorphism (Q576R) is associated with higher total IgE levels in
      Spanish patients with family history of atopy].
AB  - BACKGROUND AND OBJECTIVE: Atopy is a common immunological disorder underlying
      allergic rhinitis, atopic dermatitis and allergic asthma. There is an association
      between atopy and the polymorphism Q576R in the IL4RA gene. The aim of this study
      is to analyze the allelic distribution of the Q576R polymorphism in an atopic and
      non atopic population and the relationship with total IgE levels and the family
      history of atopy. PATIENTS AND METHOD: Q576R polymorphism of IL4RA gene was
      analyzed by PCR-restriction fragment length polymorphism (RFLP) using MspI
      restriction enzyme in 154 patients from the Allergy Department of the University
      Hospital of Salamanca. RESULTS: We have not found an association between the R576
      allele and higher serum IgE levels nor atopy in this population. Nevertheless,
      there is an association between this allele and IgE levels in patients with
      positive skin prick test and family history of atopy. CONCLUSIONS: Our results
      suggest that the R576 allele could characterize a specific group of patients with
      a familial history of atopy in whom the presence of this allele may be related to
      higher levels of serum IgE.

PMID- 15737302
TI  - [Measuring blood pressure in the forearm of obese patients: concordance with arm
      measurement].
AB  - BACKGROUND AND OBJECTIVE: The occasional forearm blood pressure (BP) measurement
      has been accepted for some obese patients. However, few studies have compared the
      concordance between arm and forearm BP measurements. Our aim was to know whether
      the forearm BP measurement displays a good concordance with the arm BP
      measurement in obese patients. SUBJECTS AND METHOD: Cross-sectional descriptive
      study in an ambulatory setting. By means of convenience sampling, a sample of 54
      patients with a body mass index > 26 kg/m2 was selected. The study unit was the
      upper limb (n = 108). BP was measured 3 times in each arm and forearm (12
      measurements in each patient using an automated validated device OMRON 705CP) in
      a randomized order. RESULTS: Women: 77.8%; mean (SD) aged: 60.2 (12.7) years;
      body mass index: 38.6 (5.5) kg/m2; 79.6% were hypertensive. BP was higher in
      forearm than in arm: mean (SD) 137.7 (16.9) mmHg versus 132.1 (18) mmHg, for
      systolic (S) BP (p < 0.001) and 79.8 (11.2) mmHg versus 78.3 (9.9) mmHg for
      diastolic (D) BP (p = 0.04), respectively. Intraclass correlation coefficients
      for arm/forearm measurements were 0.83 (95% confidence interval [CI], 0.77-0.88)
      and 0.74 (95% CI, 0.65-0.82) for SBP and DBP, respectively. Mean differences
      between arm and forearm measurements were 5.5 mmHg (95% CI, -14.5 to 25.5) mmHg
      for SBP and 1.53 mmHg [95% CI, -13.5 to 16.5] for DBP. CONCLUSIONS: BP
      differences between arm/forearm measurements are clinically outstanding.
      Therefore, forearm BP measurement does not seem advisable in obese patients.

PMID- 15737303
TI  - [Knowledge and practice].

PMID- 15737304
TI  - [Limitations of blood pressure measurement outside the arm].

PMID- 15737305
TI  - [Spain tobacco industry strategies: lobby marketing and advertising for an
      addictive product].

PMID- 15737306
TI  - [Genetic basis of tobacco dependence].
AB  - Dependence on tobacco is one of the most important health problems in our society
      due to the direct relationship with lung cancer. Early studies in twins revealed
      that genetic factors modify the susceptibility to develop tobacco dependence.
      Different studies are underway to try to find an association between
      polymorphisms of genes involved either in nicotine metabolization or in neural
      transmission and the initiation and maintenance of the dependence on tobacco.
      Here we review the studies performed so far and discuss new perspectives for
      future studies.

PMID- 15737307
TI  - [The value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG
      PET) in diagnosis of neoplastic diseases].
AB  - Positron emission tomography (PET) has the ability to detect cancer based on
      molecular and biochemical processes within the tumor tissues. The most widely
      used radiotracer in oncology at this time is the glucose analogue 18F-fluoro-2
      deoxy-D-glucose (18F-FDG). Like glucose, 18F-FDG is transported into cells by a
      glucose transporter protein and rapidly converted into 18F-FDG-6-phosphate. PET
      imaging with 18F-FDG is able to diagnose, stage, and restage many cancers with
      accuracies ranging from 80% to 90%. Responses to therapy can be identified
      earlier and with greater accuracy than is possible with anatomic imaging
      modalities. The prognostic information available through 18F-FDG PET is superior
      to that of conventional imaging for many cancers. The aim of this review article
      is to show the most promising clinical indications for the use of PET in
      oncology.

PMID- 15737309
TI  - [Limitations and subterfuges of criticism of evidence based medicine].

PMID- 15737311
TI  - [Red sea coral sting].

PMID- 15737313
TI  - [Club drugs: new challenges for the emergency departments].

PMID- 15737314
TI  - [Methodological jargon made easier to surgeons].

PMID- 15737315
TI  - [Nonoperative management of complex hepatic injuries].

PMID- 15737316
TI  - [Pseudomyxoma peritonei: new concept and new therapeutic approach].
AB  - Pseudomyxoma peritonei is a rare disease, usually diagnosed after the discover of
      "jelly belly" by laparotomy. With the progress of immunohistochemistry, most
      authors now acknowledge the appendix to be the principal origin of this disease.
      Pseudomyxoma peritonei need to considered as border line malignant disease
      because of its inevitable persistence and progression without adapted therapeutic
      approach: cytoreductive surgery combined with perioperative intraperitoneal
      chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative
      intraperitoneal chemotherapy) into specialized centres. The principal prognostic
      factors are the prior surgical history, the completeness of cytoreduction and
      especially the histopathologic grade.

PMID- 15737318
TI  - [Endoscopic thyroidectomy. A preliminary report including 40 patients].
AB  - AIM OF THE STUDY: To demonstrate the feasibility of endoscopic thyroidectomy for
      unilateral lobectomy and isthmectomy. MATERIAL AND METHODS: [corrected] This
      prospective study included 40 patients operated on between January 1999 and March
      2005 by a total endoscopic approach. Only lobectomies and isthmectomies were
      performed for nodules inferior to 3 cm in diameter. RESULTS: Forty patients (36
      females, 4 males) underwent 35 lobectomies and five isthmectomies. Twenty-four
      patients were operated on without ultrasonic shears (US) the rate of conversion
      in this group was 33%. Sixteen patients were operated on with US: the rate of
      conversion was 0%. In the second group, the operative time was decreasing to the
      half, range 45 to 90 minutes. In both the two groups, there were no morbidity: no
      extensive emphysema, no hematoma, no wound abscess, no cord vocal palsy. The
      median hospital stay was 1,75 days. After three months of follow up, all the
      patients were satisfied, especially concerning the cosmetic results and the short
      recovery time. CONCLUSIONS: Endoscopic thyroidectomy is feasible and safe for
      performing lobectomies and isthmectomies. In the near future, it could be
      extended to bilateral goitres in selected patients.

PMID- 15737317
TI  - [Severe blunt liver injury: reappraisal of criteria for nonoperative management
      decision. Experience with 88 cases].
AB  - AIM OF THE STUDY: To analyze the predictive value of computed tomography (CT) and
      initial physiologic and laboratory data findings in the immediate operative (OP)
      or non-operative (NOP) management of blunt liver injury (BL). METHODS: Eighty
      eight BL, grade III (51), grade IV (28) and nine grade V (9), aged 26.2 years (16
      75) were identified. Hemoperitoneum on CT, hemodynamic status, physiologic and
      laboratory data <24 hours or preoperative (transfusion, vascular filling) and
      follow-up >48 hours were analyzed. RESULTS: Data of 71/88 (80%) NOP and 17/88
      (20%) OP patients were reviewed. A secondary laparotomy or laparoscopy was
      necessary in 11/71 TNO. Six OP (35%) and 1 NOP patients died. Blood units
      transfused were 1.33 (0-10) vs 5.9 (0-22) and vascular filling 1.45 (0.5-5.5) vs
      3.6L (2-12) (P<10(-6), P<4.10(-3) respectively). NOP patients had less severe
      hemoperitoneum (31 vs 94%, P<10(-5)) and hemodynamic instability (8.5 vs 94%,
      P<10(-4)). But, there was an overlap of values of blood units transfused, amount
      of vascular filling and initial haemoglobin levels between NOP and OP patients
      and among CT grades of liver injury. No cut-off values could be determined: 33%
      NOP received >4 blood units and >3 L vascular filling; 30% had severe
      hemoperitoneum. In OP group 23.5% patients had lower values and no severe
      hemoperitoneum. CONCLUSION: In the management of BL, vascular filling and blood
      transfusion increased with the grade of CT liver injury and were globally more
      elevated in the operative group but did not individually correlate with
      hemodynamic stability and did not authorize, by themselves, to decide between
      operative versus non-operative management.

PMID- 15737319
TI  - [Cervical and upper-third thoracic oesophageal carcinoma: a single pathological
      entity?].
AB  - AIM OF THE STUDY: Cervical and upper-third thoracic oesophageal carcinomas are
      considered as a single pathological entity. The aim of this study was to compare
      postoperative and oncological results after surgical resection in these two
      locations. MATERIAL AND METHODS: Postoperative and oncological results were
      compared retrospectively in 155 patients who underwent surgery for carcinoma of
      the cervical (C group, n = 21) or upper-third thoracic (TS group, n = 134)
      oesophagus. RESULTS: The two groups were comparable regarding the pre-,
      peroperative and histological data. Postoperative mortality and morbidity rates
      in the C and TS groups were 4.8% and 10.4% (P= 0.413) and 57.1 and 50.7% (P=
      0.585), respectively. R0 resection and recurrence rates were 61.9% and 73.1% (P=
      0.289) and 50.0% and 51.1% (P= 0.941), respectively. Five-year survival rates
      were 0% and 35% in the overall population (P= 0.098) and 0 and 49% in the R0
      population (P= 0.047), respectively. By multivariate analysis, cervical location
      of the tumour was found to be an independent factor of poor prognosis (relative
      risk= 3.1, 95% confidence interval= 1.3-7.8, P= 0.014). CONCLUSION: Prognosis
      after surgical resection of cervical oesophagus carcinoma is very poor. Surgery
      in this location should be proposed in case of chemoradiation failure.

PMID- 15737320
TI  - [Perforated gastric ulcer: closure or gastrectomy?].

PMID- 15737321
TI  - [Anorectal Buschke-Lowenstein tumor. (Three cases report)].
AB  - Buschke-Lowenstein tumor or giant condyloma acuminata is characterized by a
      proliferation locally aggressive with extensive tissue destruction. We report
      three cases of Buschke-Lowenstein tumor with anorectal localization. The
      histology is characterized by papillomatosis and endo or exophytic acanthosis
      secondary to papillomavirus. The variety of treatment regimens applied do not
      allow formulation of definitive therapeutic guidelines.

PMID- 15737322
TI  - [Colonic actinomycosis: report of a case and review of the literature].
AB  - Actinomycosis is a chronic granulomatosis infection caused by a Gram positive
      anaerobic bacteria, Actinomyces. Abdominal localizations are rare and simulated a
      malignant process. The difficulties of diagnosis are usually leading to surgical
      resection. We report a colonic actinomycosis case of a 62-year-old woman with a
      abdominal tumor and diagnosed after surgical resection.

PMID- 15737323
TI  - [Primary hydatid cyst of adrenal gland. Report of two cases].
AB  - Primary hydatid cyst of adrenal gland is still an exceptional localization. The
      adrenal gland is an uncommon site even in our country in which echinococcal
      disease is endemic. We report two cases of primary hydatid cyst of adrenal gland
      presented with isolated abdominal pain. The diagnosis was based on CT-scan, which
      showed a cystic mass of respectively the right and left adrenal gland with a
      calcified wall. The echinococcal immunologic test (Elisa) was positive in one
      case. The surgical treatment consisted on a total resection of the cyst, without
      rupture of the cystic wall and preserving the gland. The diagnosis was confirmed
      on the macroscopic examination of the resected pieces. In the first case the cyst
      was multilocular filled with daughter cysts and in the second case the cyst was
      unilocular filled with hydatid membrane and clear fluid. In the two cases, the
      postoperative course was uneventful. No recurrence had occurred respectively
      after 24 months and 36 months of follow up.

PMID- 15737324
TI  - [Perioperative care in digestive surgery. Guidelines for the French society of
      digestive surgery (SFCD)].

PMID- 15737325
TI  - [Local excision of rectal cancer for cure].
AB  - Local excision of rectal cancer is advocated for cure only in selected patients.
      It should be done according to specific standards and needs close follow up. The
      transanal technique is well defined and indicated for posterior rectal wall
      tumours. Otherwise, technical modifications or microsurgery can be performed. The
      transacral approach should be abandoned.

PMID- 15737326
TI  - Detection of motional heterogeneities in lipid bilayer membranes by dual probe
      fluorescence correlation spectroscopy.
AB  - We report the detection of heterogeneities in the diffusion of lipid molecules
      for the three-component mixture dipalmitoyl-PC/dilauroyl-PC/cholesterol, a
      chemically simple lipid model for the mammalian plasma membrane outer leaflet.
      Two-color fluorescence correlation spectroscopy (FCS) was performed on giant
      unilamellar vesicles (GUVs) using fluorescent probes that have differential lipid
      phase partition behavior--DiO-C18:2 favors disordered fluid lipid phases, whereas
      DiI-C20:0 prefers spatially ordered lipid phases. Simultaneously-obtained
      fluorescence autocorrelation functions from the same excitation volume for each
      dye showed that, depending on the lipid composition of this ternary mixture, the
      two dyes exhibited different lateral mobilities in regions of the phase diagram
      with previously proposed submicroscopic two-phase coexistence. In one-phase
      regions, both dyes reported identical diffusion coefficients. Two-color FCS thus
      may be detecting local membrane heterogeneities at size scales below the optical
      resolution limit, either due to short-range order in a single phase or due to
      submicroscopic phase separation.

PMID- 15737327
TI  - Methionine-rich repeat proteins: a family of membrane-associated proteins which
      contain unusual repeat regions.
AB  - We report the protein isolation, cloning and characterization of members of an
      unusual protein family, which comprise the most abundant proteins present in the
      squid eye. The proteins in this family have a range of molecular weights from 32
      to 36 kDa. Electron microscopy and detergent solubilization demonstrate that
      these proteins are tightly associated with membrane structures where they may
      form tetramers. Despite this, these proteins have no stretches of hydrophobic
      residues that could form typical transmembrane domains. They share an unusual
      protein sequence rich in methionine, and contain multiple repeating motifs. We
      have therefore named these proteins Methionine-Rich Repeat Proteins (MRRPs). The
      use of structure prediction algorithms suggest very little recognized secondary
      structure elements. At the time of cloning no sequence or structural homologues
      have been found in any database. We have isolated three closely related cDNA
      clones from the MRRP family. Coupled in vitro transcription/translation of the
      MRRP clones shows that they encode proteins with molecular masses similar to
      components of native MRRPs. Immunoblot analysis of these proteins reveals that
      they are also present in squid brain, optic lobe, and heart, and also indicate
      that MRRP-like protein motifs may also exist in mammalian tissues. We propose
      that MRRPs define a family of important proteins that have an unusual mode of
      attachment or insertion into cell membranes and are found in evolutionarily
      diverse organisms.

PMID- 15737328
TI  - The interactions of antimicrobial peptides derived from lysozyme with model
      membrane systems.
AB  - Two peptides, RAWVAWR-NH2 and IVSDGNGMNAWVAWR-NH2, derived from human and chicken
      lysozyme, respectively, exhibit antimicrobial activity. A comparison between the
      L-RAWVAWR, D-RAWVAWR, and the longer peptide has been carried out in membrane
      mimetic conditions to better understand how their interaction with lipid and
      detergent systems relates to the reported higher activity for the all L-peptide.
      Using CD and 2D 1H NMR spectroscopy, the structures were studied with DPC and SDS
      micelles. Fluorescence spectroscopy was used to study peptide interactions with
      POPC and POPG vesicles and DOPC, DOPE, and DOPG mixed vesicle systems. Membrane
      peptide interactions were also probed by ITC and DSC. The ability of fluorescein
      labeled RAWVAWR to rapidly enter both E. coli and Staphylococcus aureus was
      visualized using confocal microscopy. Reflecting the bactericidal activity, the
      long peptide interacted very weakly with the lipids. The RAWVAWR-NH2 peptides
      preferred lipids with negatively charged headgroups and interacted predominantly
      in the solvent-lipid interface, causing significant perturbation of membrane
      mimetics containing PG headgroups. Peptide structures determined by 1H NMR
      indicated a well-ordered coiled structure for the short peptides and the C
      terminus of the longer peptide. Using each technique, the two enantiomers of
      RAWVAWR-NH2 interacted in an identical fashion with the lipids, indicating that
      any difference in activity in vivo is limited to interactions not involving the
      membrane lipids.

PMID- 15737329
TI  - Intestinal uptake of nateglinide by an intestinal fluorescein transporter.
AB  - Nateglinide, a novel oral hypoglycemic agent, rapidly reaches its maximum serum
      concentration after oral administration, suggesting that it is rapidly absorbed
      in the intestine. However, nateglinide itself is not transported by MCT1 or
      PEPT1. The aim of this study was to characterize the transporters on the apical
      side of the small intestine that are responsible for the rapid absorption of
      nateglinide. It has been reported that the uptake of fluorescein by Caco-2 cells
      occurs via an H+-driven transporter and that the intestinal fluorescein
      transporter is probably not MCT1. We examined the contribution of the fluorescein
      transporter to the uptake of nateglinide by Caco-2 cells. Fluorescein
      competitively inhibited H+-dependent nateglinide uptake. All of fluorescein
      transporter inhibitors examined reduced the uptake of nateglinide. Furthermore,
      nateglinide inhibited fluorescein uptake. We conclude that the intestinal
      nateglinide/H+ cotransport system is identical to the intestinal fluorescein/H+
      cotransport system.

PMID- 15737330
TI  - Pertussis toxin-sensitive modulation of glutamate transport by endothelin-1 type
      A receptors in glioma cells.
AB  - Endothelin-1 (ET-1) is a 21 amino acids peptide that exerts several biological
      activities through interaction with specific G-protein coupled receptors.
      Increased ET-1 expression is frequently associated with pathological situations
      involving alterations in glutamate levels. In the present study, a brief exposure
      to ET-1 was found to increase aspartate uptake in C6 glioma cells, which
      endogenously express the neuronal glutamate transporter EAAC1 (pEC50 of 9.89).
      The stimulatory effect of ET-1 mediated by ETA receptors corresponds to a 62%
      increase in the Vmax with no modification of the affinity for the substrate.
      While protein kinase C activity is known to participate in the regulation of
      EAAC1, the effect of ET-1 on the glutamate uptake was found to be independent of
      this kinase activation. In contrast, the inactivation of Go/i type G-protein
      dependent signaling with pertussis toxin was found to impair ET-1-mediated
      regulation of EAAC1. An examination of the cell surface expression of EAAC1 by
      protein biotinylation studies or by confocal analysis of immuno-fluorescence
      staining demonstrated that ET-1 stimulates EAAC1 translocation to the cell
      surface. Hence, the disruption of the cytoskeleton with cytochalasin D prevented
      ET-1-stimulated aspartate uptake. Together, the data presented in the current
      study suggest that ET-1 participates in the acute regulation of glutamate
      transport in glioma cells. Considering the documented role of glutamate
      excitotoxicity in the development of brain tumors, endothelinergic system
      constitutes a putative target for the pharmacological control of glutamate
      transmission at the vicinity of glioma cells.

PMID- 15737331
TI  - Calorimetric and spectroscopic studies of the phase behavior and organization of
      lipid bilayer model membranes composed of binary mixtures of
      dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol.
AB  - The thermotropic phase behavior of hydrated bilayers derived from binary mixtures
      of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol
      (DMPG) was investigated by differential scanning calorimetry, Fourier-transform
      infrared spectroscopy and 31P-nuclear magnetic resonance spectroscopy. Binary
      mixtures of DMPC and DMPG that have not been annealed at low temperatures exhibit
      broad, weakly energetic pretransitions (approximately 11-15 degrees C) and highly
      cooperative, strongly energetic gel/liquid-crystalline phase transitions
      (approximately 23-25 degrees C). After low temperature incubation, these mixtures
      also exhibit a thermotropic transition form a lamellar-crystalline to a lamellar
      gel phase at temperatures below the onset of the gel/liquid-crystalline phase
      transition. The midpoint temperatures of the pretransitions and gel/liquid
      crystalline phase transitions of these lipid mixtures are both maximal in
      mixtures containing approximately 30 mol% DMPG but the widths and enthalpies of
      the same thermotropic events exhibit no discernable composition dependence. In
      contrast, thermotropic transitions involving the Lc phase exhibit a very strong
      composition dependence, and the midpoint temperatures and transition enthalpies
      are both maximal with mixtures containing equimolar amounts of the two lipids.
      Our spectroscopic studies indicate that the Lc phases formed are structurally
      similar as regards their modes of hydrocarbon chain packing, interfacial
      hydration and hydrogen-bonding interactions, as well as the range and amplitudes
      of the reorientational motions of their phosphate headgroups. Our results
      indicate that although DMPC and DMPG are highly miscible, their mixtures do not
      exhibit ideal mixing. We attribute the non-ideality in their mixing behavior to
      the formation of preferential PC/PG contacts in the Lc phase due to the combined
      effects of steric crowding of the DMPC headgroups and charge repulsion between
      the negatively charged DMPG molecules.

PMID- 15737332
TI  - Melatonin strongly interacts with zwitterionic model membranes--evidence from
      Fourier transform infrared spectroscopy and differential scanning calorimetry.
AB  - Interactions of melatonin with zwitterionic dipalmitoyl phosphatidylcholine
      (DPPC) multilamellar liposomes (MLVs) were investigated as a function of
      temperature and melatonin concentration (1-30 mol%) by using two noninvasive
      techniques, namely Fourier transform infrared (FTIR) spectroscopy and
      differential scanning calorimetry (DSC). The investigation of the C-H, CO, and
      PO2- antisymmetric double stretching modes in FTIR spectra and DSC studies reveal
      that melatonin changes the physical properties of the DPPC bilayers by decreasing
      the main phase transition temperature, abolishing the pretransition, ordering the
      system in the gel phase, and increasing the dynamics of the system both in the
      gel and liquid crystalline phases. It also causes significant decrease in the
      wavenumber for the CO stretching and PO2- antisymmetric double bond stretching
      bands, which indicates strong hydrogen bonding The results imply that melatonin
      locates in the interfacial region of the membrane. Furthermore, in the DSC curve,
      more than one signal is observed at high melatonin concentrations (24 and 30
      mol%), which indicates melatonin-induced phase separation in DPPC membranes.

PMID- 15737333
TI  - Electrophysiological and molecular identification of hepatocellular volume
      activated K+ channels.
AB  - Although K+ channels are essential for hepatocellular function, it is not known
      which channels are involved in the regulatory volume decrease (RVD) in these
      cells. We have used a combination of electrophysiological and molecular
      approaches to describe the potential candidates for these channels. The dialysis
      of short-term cultured rat hepatocytes with a hypotonic solution containing high
      K+ and low Cl- concentration caused the slow activation of an outward, time
      independent current under whole-cell configuration of the patch electrode voltage
      clamp. The reversal potential of this current suggested that K+ was the primary
      charge carrier. The swelling-induced K+ current (IKvol) occurred in the absence
      of Ca2+ and was inhibited with 1 microM Ca2+ in the pipette solution. The
      activation of IKvol required both Mg2+ and ATP and an increasing concentration of
      Mg-ATP from 0.25 through 0.5 to 0.9 mM activated IKvol increasingly faster and to
      a larger extent. The KCNQ1 inhibitor chromanol 293B reversibly depressed IKvol
      with an IC50 of 26 microM. RT-PCR detected the expression of members of the KCNQ
      family from KCNQ1 to KCNQ5 and of the accessory proteins KCNE1 to KCNE3 in the
      rat hepatocytes, but not KCNQ2 and KCNE2 in human liver. Western blotting showed
      KCNE3 expression in a plasma membrane-enriched fraction from rat hepatocytes. The
      results suggest that KCNQ1, probably with KCNE2 or KCNE3 as its accessory unit,
      provides a significant fraction of IKvol in rat hepatocytes.

PMID- 15737334
TI  - Monovalent cation conductance in Xenopus laevis oocytes expressing hCAT-3.
AB  - hCAT-3 (human cationic amino acid transporter type three) was investigated with
      both the two-electrode voltage clamp method and tracer experiments. Oocytes
      expressing hCAT-3 displayed less negative membrane potentials and larger voltage
      dependent currents than native or water-injected oocytes did. Ion substitution
      experiments in hCAT-3-expressing oocytes revealed a large conductance for Na+ and
      K+. In the presence of L-Arg, voltage-dependent inward and outward currents were
      observed. At symmetrical (inside/outside) concentrations of L-Arg, the
      conductance of the transporter increased monoexponentially with the L-Arg
      concentrations; the calculated Vmax and KM values amounted to 8.3 microS and 0.36
      mM, respectively. The time constants of influx and efflux of [3H]L-Arg, at
      symmetrically inside/outside L-Arg concentrations (1 mM), amounted to 79 and 77
      min, respectively. The flux data and electrophysiological experiments suggest
      that the transport of L-Arg through hCAT-3 is symmetric, when the steady state of
      L-Arg flux has been reached. It is concluded that hCAT-3 is a passive transport
      system that conducts monovalent cations including L-Arg. The particular role of
      hCAT-3 in the diverse tissues remains to be elucidated.

PMID- 15737335
TI  - Synthesis and initial characterization of FGFR3 transmembrane domain:
      consequences of sequence modifications.
AB  - Receptor Tyrosine Kinases (RTKs) conduct biochemical signals via lateral
      dimerization in the plasma membrane, and defects in their dimerization lead to
      unregulated signaling and disease. RTK transmembrane (TM) domains are proposed to
      play an important role in the process, underscored by the finding that single
      amino acids mutations in the TM domains can induce pathological phenotypes.
      Therefore, many important questions pertaining to the mode of signal transduction
      and the mechanism of pathology induction could be answered by studying the
      chemical-physical basis behind RTK TM domain dimerization and the interactions of
      RTK TM domains with lipids in model bilayer systems. As a first step towards this
      goal, here we report the synthesis of the TM domain of fibroblast growth factor
      receptor 3 (FGFR3), an RTK that is crucial for skeletal development. We have used
      solid phase peptide synthesis to produce two peptides: one corresponding to the
      membrane embedded segment and the naturally occurring flanking residues at the N-
      and C-termini (TMwt), and a second one in which the flanking residues have been
      substituted with diLysines at the termini (TMKK). We have demonstrated that the
      hydrophobic FGFR3 TM domain can be synthesized for biophysical studies with high
      yield. The protocol presented in the paper can be applied to the synthesis of
      other RTK TM domains. As expected, the Lys flanks decrease the hydrophobicity of
      the TM domain, such that TMKK elutes much earlier than TMwt during reverse phase
      HPLC purification. The Lysines have no effect on peptide solubility in SDS and on
      peptide secondary structure, but they abolish peptide dimerization on SDS gels.
      These results suggest that caution should be exercised when modifying RTK TM
      domains to render them more manageable for biophysical studies.

PMID- 15737336
TI  - Nucleotide dissociation from NBD1 promotes solute transport by MRP1.
AB  - MRP1 transports glutathione-S-conjugated solutes in an ATP-dependent manner by
      utilizing its two NBDs to bind and hydrolyze ATP. We have found that ATP binding
      to NBD1 plays a regulatory role whereas ATP hydrolysis at NBD2 plays a dominant
      role in ATP-dependent LTC4 transport. However, whether ATP hydrolysis at NBD1 is
      required for the transport was not clear. We now report that ATP hydrolysis at
      NBD1 may not be essential for transport, but that the dissociation of the NBD1
      bound nucleotide facilitates ATP-dependent LTC4 transport. These conclusions are
      supported by the following results. The substitution of the putative catalytic
      E1455 with a non-acidic residue in NBD2 greatly decreases the ATPase activity of
      NBD2 and the ATP-dependent LTC4 transport, indicating that E1455 participates in
      ATP hydrolysis. The mutation of the corresponding D793 residue in NBD1 to a
      different acidic residue has little effect on ATP-dependent LTC4 transport. The
      replacement of D793 with a non-acidic residue, such as D793L or D793N, increases
      the rate of ATP-dependent LTC4 transport. Along with their higher transport
      activities, their Michaelis constant Kms (ATP) are also higher than that of wild
      type. Coincident with their higher Kms (ATP), their Kds derived from ATP binding
      are also higher than that of wild-type, implying that the rate of dissociation of
      the bound nucleotide from the mutated NBD1 is faster than that of wild-type.
      Therefore, regardless of whether the bound ATP at NBD1 is hydrolyzed or not, the
      release of the bound nucleotide from NBD1 may bring the molecule back to its
      original conformation and facilitate the protein to start a new cycle of ATP
      dependent solute transport.

PMID- 15737337
TI  - Ovine lentivirus-associated leucomyelitis in naturally infected North American
      sheep.
AB  - Leucomyelitis was the predominant feature in four North American adult sheep
      (cases 1-4) with ovine lentivirus (OvLV) infection. All four animals were OvLV
      seropositive and a syncytogenic virus consistent with OvLV was isolated from the
      brain of case 3 and the lungs of case 4. Clinically, the sheep had dyspnoea and
      neurologic signs of varying severity. Changes in the central nervous system
      included asymmetrical meningoleucomyelitis with white matter degeneration in all
      four sheep and scattered foci of leucoencephalitis in periventricular,
      subependymal and other white matter areas of the brain of the three animals
      (cases 1, 2 and 4) for which the brain was examined. In the lungs of two sheep
      (cases 3 and 4), there was lymphoid interstitial pneumonia with marked lymphoid
      hyperplasia. The viral capsid antigen (p25) was detected by immunohistochemistry
      (IHC) in sections of lung, brain and spinal cord of the four sheep and OvLV RNA
      was detected by in-situ hybridization (ISH) in lung and spinal cord samples. The
      results confirm the usefulness of the IHC and ISH for differential diagnosis of
      visna.

PMID- 15737338
TI  - Primary isolation of the bovine spongiform encephalopathy agent in mice: agent
      definition based on a review of 150 transmissions.
AB  - In the epizootic of bovine spongiform encephalopathy (BSE) in Great Britain, the
      cattle in which a positive diagnosis was made numbered almost 180 000, but strain
      characterization was performed on only a very small sample of these cases. This
      report describes the results of BSE transmission to Prnp(a) mice from 150
      transmission experiments at the Veterinary Laboratories Agency (VLA) over the
      last decade. These data, derived from a large sample of BSE-affected cattle,
      confirmed previous reports that show no evidence for diversity in BSE isolates.
      The agent was readily transmitted to mice, with a mean incubation period of 408
      days in the RIII strain. Because the incubation period was related to the titre
      of the inoculum, it is not a reliable characteristic of strain type on primary
      isolation. Consistent neuropathological changes associated with infection by the
      BSE agent in RIII and C57Bl mice included focal vacuolation in the dorsal
      cochlear nuclei, vacuolation of the granule cell layer of the cerebellum, absence
      of lesions in the hippocampus and in the molecular layer of the cerebellum, and a
      fine particulate distribution of disease-specific PrP (demonstrated
      immunohistochemically), with few or no amyloid plaques. These features, together
      with the conventional lesion profile, will be of use in distinguishing the agents
      of BSE and scrapie in sheep.

PMID- 15737339
TI  - Pigmented cutaneous papillomatosis (pigmented epidermal nevus) in three pug dogs;
      histopathology, electron microscopy and analysis of viral DNA by the polymerase
      chain reaction.
AB  - Canine pigmented epidermal nevus (CPEN) is a skin disorder of some breeds of dog
      characterized by multiple black plaques of the haired and non-haired skin. Three
      cases of pigmented cutaneous papillomatosis (previously described also as CPEN)
      in pug dogs were investigated histopathologically, immunohistochemically and
      electron microscopically. Additionally, DNA analyses with the polymerase chain
      reaction (PCR) were performed in two cases. Many nuclei of the stratum granulosa
      were diffusely immunolabelled for specific structural antigens of bovine
      papillomavirus (subgroup A), but nuclear inclusion bodies were not detected by
      retrospective examination of haematoxylin and eosin-stained sections of the
      affected skin. Aggregates of small numbers of viral particles (ranging from 37 to
      43 nm in diameter) with a hexagonal structure were sparsely scattered throughout
      the nuclei of some of the superficial keratinocytes. PCR amplification targeted
      for the L1 gene of papillomavirus cloned from a case of CPEN yielded an expected
      fragment of 194-bp in the two CPEN cases examined but not in a case of canine
      oral papilloma.

PMID- 15737340
TI  - Birth abnormalities in pregnant sows infected intranasally with porcine
      circovirus 2.
AB  - Six pregnant sows were inoculated intranasally at 3 weeks before the expected
      farrowing date with porcine circovirus 2 (PCV2). The PCV2-inoculated sows showed
      abortion and premature farrowing, whereas two uninfected negative control sows
      remained clinically healthy and farrowed normally. PCV2 antigen and DNA were
      detected by immunohistochemistry and in-situ hybridization, respectively, in
      lymph node, spleen, thymus, lung, tonsil and liver from both stillborn and
      liveborn piglets. Simultaneous detection of viral protein and DNA provided
      molecular evidence of PCV2 infection and replication. The experiment suggested
      that PCV2 is capable of crossing the placenta, replicating primarily in lymphoid
      tissues, and inducing reproductive failure.

PMID- 15737341
TI  - Chronic hepatitis associated with canine leishmaniosis (Leishmania infantum): a
      clinicopathological study of 26 cases.
AB  - Hepatic tissue samples were obtained from 26 dogs humanely destroyed because of
      naturally occurring leishmaniosis (Leishmania infantum). None of the animals had
      palpable hepatomegaly or any other physical finding or historical evidence
      indicative of liver failure. However, serum biochemistry revealed
      hypoalbuminaemia (6/26), increased alkaline phosphatase (ALP) activity (15/26),
      and increased concentrations of total bilirubin (2/26) and post-prandial bile
      acids (4/26). Three main histological patterns were identified. In pattern 1
      (3/26), the liver microarchitecture remained unchanged apart from the presence of
      individual or clustered macrophages in the sinusoids. In pattern 2 (20/26), there
      was multifocal, mild to moderate, granulomatous to pyogranulomatous infiltration
      of the hepatic parenchyma, particularly in the portal areas. Pattern 3 (3/26),
      which was the most severe form, was characterized by marked portal
      lymphoplasmacytic infiltration with occasional broaching of the limiting plate
      and extension into the adjacent parenchyma. In this pattern there was also mild
      portal fibrosis, together with lymphoplasmacytic aggregates within the parenchyma
      and small clusters of lymphocytes and plasma cells within the sinusoids. All
      three patterns were associated with hepatocyte vacuolation (15/26 dogs), and
      haemosiderin accumulation within the hepatocyte cytoplasm. Congestion was present
      in the liver of five dogs. No correlation was found between histopathological
      pattern and breed, sex, age, clinical manifestations, serum biochemical profile
      or parasite load in the hepatic tissue; patterns 1-3 may, however, represent
      sequential stages of hepatic leishmania infection during the chronic course of
      the disease.

PMID- 15737342
TI  - Effects of orientation, intermittent rest and vehicle cleaning during transport
      on development of transport-related respiratory disease in horses.
AB  - The effects of various factors on the inflammatory and stress response in horses
      during transportation were examined in Experiments 1 and 2, carried out in April
      and August, respectively. In Experiment 1, three groups (G1-G3) of four
      Thoroughbreds were used, and in Experiment 2, two groups (G4, G5). G1 animals
      were loaded into lorries with their heads facing forwards (FF) and given periods
      of short rest (SR) (30 min for every 4 h driven). G2 horses were loaded facing
      rearwards (FR) and given SR. G3 horses were FF and given periods of long rest
      (LR) (2 h rest for every 4 h driven). G4 horses were transported FF with hay
      suspended in front of them and no cleaning of faeces or urine during rest stops.
      G5 horses were FF and given pellets instead of hay, and the lorry was cleaned and
      washed at each rest stop. G4 and G5 horses were rested for 1 h after every 5 h of
      driving. All groups were driven a distance of 1500 km, and the total journey time
      was 37 h for G1 and G2, 49 h for G3, and 40 h for G4 and G5. In Experiment 1,
      indicators of inflammatory and stress responses tended to be highest in G1,
      intermediate in G2 and lowest in G3. In Experiment 2 they tended to be higher in
      G4 than in G5. The results suggested that increasing the rest time and cleaning
      the interior of the vehicle during rest stops reduced transportation stress and
      respiratory insults, factors that may lead to respiratory disease.

PMID- 15737343
TI  - The dental pathology of northern elephant seals (Mirounga angustirostris).
AB  - Skulls (n=104) of northern elephant seals from California were examined
      macroscopically. The animals varied in age but the numbers of each sex were
      roughly equal. The majority (86%) of teeth were available for examination. The
      mandibular first premolars were the most common teeth to be congenitally absent,
      with 2.3% missing. Supernumerary teeth (usually a supplemental mandibular molar)
      were associated with only 1.4% of normal teeth (or empty alveolar sockets). At
      least one persistent deciduous tooth was present in 38% of skulls, 70% of which
      were juvenile skulls. The majority (95.8%) of premolars had the type 2a tooth
      form, with only 3.8% and 0.5% of type 2b and 2c, respectively. Forty-six skulls,
      of which 43 were from adults, showed signs of attrition. Tooth fractures were
      uncommon, affecting only 33 teeth (1.2%). One skull showed an "incremental line"
      suggestive of enamel hypoplasia. Periodontal hard tissue lesions were seen in
      44.3% of all teeth present (46.0% of skulls). Six cases of periapical disease
      with bone loss were observed.

PMID- 15737344
TI  - Pathogenesis of swine influenza virus subtype H1N2 infection in pigs.
AB  - The purpose of this study was to elucidate pathogenesis and viral distribution in
      pigs infected with swine influenza virus subtype H1N2, over a period of 10 days,
      by morphometric analysis and in-situ hybridization. Fifteen colostrum-deprived
      pigs aged 3 weeks were inoculated intranasally with virus. Pneumonia was severe
      at 1 day post-inoculation (dpi), moderate at 3 and 5 dpi, and mild at 7 and 10
      dpi. The pulmonary lesion score was correlated with the score of cells positive
      by in-situ hybridization for swine influenza virus (r(s)= 0.9114, P< 0.05). The
      distribution of swine influenza virus varied according to the duration of
      infection. At 1 and 3 dpi, hybridization signals were detected mainly in the
      bronchial and bronchiolar epithelial cells, but they were detected mainly in the
      pneumocytes and macrophages (alveolar and interstitial) at 7 and 10 dpi. The
      results confirmed that swine influenza virus subtype H1N2, isolated in Korea, is
      a virulent pathogen causing severe pneumonia.

PMID- 15737345
TI  - Attaching-effacing lesions associated with Escherichia coli O157:H7 and other
      bacteria in experimentally infected conventional neonatal goats.
AB  - Four conventionally reared goats aged 6 days were inoculated orally with
      approximately 10(10) colony-forming units (cfu) of a non-verotoxigenic strain of
      Escherichia coli O157:H7. All remained clinically normal. Tissues were sampled
      under terminal anaesthesia at 24 (two animals), 48 and 72 h post-inoculation
      (hpi). E. coli O157:H7 was cultured from the ileum, caecum, colon and rectum of
      all animals, but the number of bacteria recovered at these sites varied between
      animals. Attaching-effacing (AE) lesions associated with O157 organisms, as
      confirmed by immunolabelling, were observed in the ileum of one of the two
      animals examined at 24 hpi, and in the ileum, caecum and proximal colon of an
      animal examined at 72 hpi. E. coli O157 organisms were detected at > or =10(5)
      cfu/g of tissue at these sites. In addition, AE lesions associated with
      unidentified bacteria were observed at various sites in the large bowel of the
      same animals. Lesions containing both E. coli O157 and unidentified bacteria (non
      O157) were not observed. Non-O157 AE lesions were also observed in the large
      bowel of one of two uninoculated control animals. This indicated that three (one
      control and two inoculated) animals were colonized with an unidentified AE
      organism before the commencement of the experiment. The O157-associated AE
      lesions were observed only in animals colonized by non-O157 AE organisms and this
      raises questions about individual host susceptibility to AE lesions and whether
      non-O157 AE organisms influence colonization by E. coli O157.

PMID- 15737346
TI  - H-ras immunohistochemical expression and molecular analysis of urinary bladder
      lesions in grazing adult cattle exposed to bracken fern.
AB  - Chronic ingestion of bracken fern (Pteridium spp.) by cattle produces upper
      alimentary tract and urinary bladder tumours causing a syndrome called bovine
      enzootic haematuria (BEH). Previous studies demonstrated ptaquiloside-DNA adducts
      and mutations in the h-ras gene in ileal epithelial cells of bracken fern-fed
      calves. Systematic inspection of the bladder mucosa of grazing cattle (n=126)
      from bracken-fern areas was carried out in a slaughterhouse. Of the 126
      slaughterhouse cattle, 46 showed macroscopical lesions of the bladder. These
      bladders, together with six others known to have BEH, were examined
      histopathologically and by H-ras immunohistochemistry. Thirteen affected bladders
      were also examined by H-ras molecular analysis to detect mutations. Macroscopical
      and histological study of urinary bladder lesions found at the slaughterhouse
      revealed chronic cystitis (34.1%) and tumours (2.4%). There was significantly
      increased immunohistochemical expression of H-ras (P<0.05) in chronic cystitis (H
      ras=53.24%) and bladder tumours (H-ras=63.60%) as compared with normal urinary
      bladders (H-ras=4.32%). A silent mutation (D38D) was detected in one animal with
      a mixed bladder tumour. The prevalence of urinary bladder lesions (chronic
      cystitis and tumours) obtained at the slaughterhouse was higher than expected.
      This study demonstrates that close inspection of urinary bladders of adult
      grazing cows is necessary to prevent possible human exposure to bracken-fern
      carcinogens. The absence of mutations in the codons of h-ras studied did not
      exclude the presence of polymorphisms in other regions of the gene (promoter or
      regulation sequences) or in other genes (belonging or not to the ras family) that
      significantly affect the H-ras protein.

PMID- 15737347
TI  - Clinicopathological characterization of monkey B virus (Cercopithecine
      herpesvirus 1) infection in mice.
AB  - The purpose of this study was to establish a small animal model for monkey B
      virus (BV) infection. Mice were inoculated intramuscularly with several BV
      isolates. Comparisons were based upon the doses required to produce infection
      (ID50), non-central nervous system (CNS) clinical disease (CS50), CNS disease
      (CNSD50) and lethal effect (LD50). Strains differed in respect of the dose
      required to produce clinical disease in BALB/c mice. C57BL/6 mice were more
      resistant than BALB/c mice to CNS disease. Skin lesions at the inoculation site
      consisted of epidermal necrosis, ulceration, serocellular crusts and underlying
      dermatitis. CNS lesions included marked inflammation in the ipsilateral dorsal
      root ganglion and lumbar spinal cord (point of viral entry). The distribution of
      the lumbar spinal cord lesions suggested viral entry via sensory afferent
      neurons, ventral motor tracts, or both. The lesions in the more cranial spinal
      cord segments suggested ascension to the brain via bilateral spinothalamic and
      spinoreticular tracts. Brain lesions included encephalitis with neuronal necrosis
      and white matter destruction located consistently at the base of the brainstem,
      the reticular system, and rostrally to the thalamus and hypothalamus. Viral
      antigen was detected immunohistochemically in the lesions. The results indicated
      an ascending encephalomyelitis syndrome similar to that produced by BV in man.

PMID- 15737349
TI  - Synaptophysin: an immunohistochemical marker for animal dysautonomias.
AB  - Equine and feline dysautonomias are characterized histopathologically by
      degenerating neurons with chromatolysis, pyknotic and sometimes eccentric nuclei,
      and loss of Nissl substance in the peripheral autonomic ganglia. Because it may
      be difficult to distinguish pathological from post-mortem changes in affected
      ganglia by histopathological examination, synaptophysin was evaluated as an
      immunohistochemical marker. Degenerating neurons showed strong intracytoplasmic
      labelling indicating abnormal accumulation of synaptophysin. It was concluded
      that synaptophysin immunohistochemistry is a helpful tool for detecting
      degenerating neurons in equine (grass sickness) and feline (Key-Gaskell syndrome)
      dysautonomias.

PMID- 15737348
TI  - Metastatic esthesioneuroblastoma in a horse.
AB  - A 17-year-old horse developed severe proptosis of the left eye over a period of
      1.5 years. At post-mortem examination a neoplasm was found involving the left
      ethmoid bone, left maxillary sinus, left orbit, left superior turbinate, and the
      left eye. Tumour cells were arranged in nests separated by a fine fibrovascular
      stroma. Immunohistochemically, the tumour cells were labelled by antibodies
      against neurofilament protein, synaptophysin, glial fibrillary acidic protein and
      S-100 protein antigen, but were negative for chromogranin A, cytokeratin and
      desmin. Electronmicroscopically, the cells showed neurosecretory granules with an
      electron-dense centre and a light halo, and microfilaments. On the basis of
      macroscopical, light microscopical and ultrastructural findings a diagnosis of a
      metastatic esthesioneuroblastoma was made.

PMID- 15737350
TI  - Parasitic lesions of bovine liver attributed to capillaria species.
AB  - Among meat inspectors in Hokkaido, Japan, the term "bovine parasitic hepatitis"
      (BPH) has long been used to refer to a hepatic disorder characterized by multiple
      small yellowish lesions. However, the aetiology is unknown. By means of detailed
      histopathological examination, fragments of parasitic worms resembling Capillaria
      were detected in nine (2.25%) of 400 livers showing BPH lesions. Histologically,
      the degenerative lesions showed eosinophilic papillary endothelial hyperplasia of
      the interlobular veins and eosinophilic membranous structures in the eosinophilic
      granulomatous areas of inflammation. These characteristic findings differed from
      those of hepatic capillariasis of other animal species. BPH was found in 5-20% of
      milk cows examined throughout Hokkaido, and was also detected in cattle from
      another prefecture and from Australia. Possibly the same parasitic disorder,
      albeit undiagnosed, is more widespread.

PMID- 15737351
TI  - A novel leucodystrophy in a dog.
AB  - A diffuse, bilaterally symmetrical leucoencephalopathy was observed in a 2-month
      old female crossbred puppy with a clinical history of progressive tetraparesis
      with front limb hypermetria, head tremor and seizures. Severe myelinolytic
      lesions with significant macrophage infiltration were confined to the white
      matter, mainly of the cerebellum and spinal cord. Moderate loss of myelin with
      severe gliosis predominated in the cerebrum. Axonal degeneration and axonal loss
      accompanied myelin degeneration. This disease was classified as a leucodystrophy.
      The clinical signs and certain features of the lesions (morphology and
      distribution), differed from those in previously described degenerative
      myelinolytic diseases in animals. The possible occurrence of the disorder in a
      littermate suggested a genetic basis.

PMID- 15737352
TI  - Tracheal carcinosarcoma (true malignant mixed tumour) in a Belgian Blue heifer.
AB  - This report describes a case of a carcinosarcoma or true malignant mixed tumour
      (salivary gland type) of the trachea in a Belgian Blue heifer. At post-mortem
      examination a nodular, well-circumscribed, firmly attached mass was found in the
      tracheal wall, severely compressing the tracheal lumen. Histologically the tumour
      was biphasic, with varying proportions of epithelial elements dispersed
      throughout a matrix showing varying degrees of myxo-chondroid and cartilaginous
      differentiation. The histological features of the tumour were consistent with a
      combination of an adenoid cystic carcinoma and a chondrosarcoma. Immunolabelling
      demonstrated smooth muscle actin in the cytoplasm of both the epithelial and
      mesenchymal components, thus fulfilling the diagnostic criteria for a mixed
      tumour. To our knowledge this is the first report of a mixed tumour of the
      trachea in a domestic animal.

PMID- 15737353
TI  - Hepatosplenic large cell immunoblastic lymphoma in a bottlenose dolphin (Tursiops
      truncatus) with high levels of polychlorinated biphenyl congeners.
AB  - This report describes a large cell immunoblastic lymphoma in a bottlenose dolphin
      found stranded alive in Gran Canaria, Spain. Diffuse infiltration of round
      neoplastic cells was observed in the splenic cords and sinuses and in hepatic
      sinusoids, resulting in moderate organ enlargement. The tumour cells
      (immunophenotype IgG+ and CD3-) showed scant, lightly eosinophilic or basophilic
      cytoplasm, distinct cell boundaries and hyperchromatic nuclei, each with one or
      more nucleoli. Mitoses were common. On the basis of histopathological,
      immunohistochemical and ultrastructural features, the tumour was classified as an
      immunoblastic lymphoma. Eleven polychlorinated biphenyl (PCB) congeners, 23
      organochlorine pesticides and 16 polycyclic aromatic hydrocarbons (PAHs) were
      detected in the blubber and liver. High concentrations of PCBs 153, 180, 138 and
      187 found in the liver may have been associated with the hepatosplenic lymphoma.

PMID- 15737354
TI  - Port activities and international environmental control in the Mediterranean.

PMID- 15737355
TI  - Effects of terrestrial runoff on the ecology of corals and coral reefs: review
      and synthesis.
AB  - This paper reviews and evaluates the current state of knowledge on the direct
      effects of terrestrial runoff on (1) the growth and survival of hard coral
      colonies, (2) coral reproduction and recruitment, and (3) organisms that interact
      with coral populations (coralline algae, bioeroders, macroalgae and heterotrophic
      filter feeders as space competitors, pathogens, and coral predators). The
      responses of each of these groups are evaluated separately against the four main
      water quality parameters: (1) increased dissolved inorganic nutrients, (2)
      enrichment with particulate organic matter, (3) light reduction from turbidity
      and (4) increased sedimentation. This separation facilitates disentangling and
      understanding the mechanisms leading to changes in the field, where many
      contaminants and many responses co-occur. The review also summarises geographic
      and biological factors that determine local and regional levels of resistance and
      resilience to degradation. It provides a conceptual aid to assess the kind of
      change(s) likely to occur in response to changing coastal water quality.

PMID- 15737356
TI  - Bacterial community and some physico-chemical characteristics in a subtropical
      mangrove environment in Bahrain.
AB  - A study of bacterial communities and some physico-chemical parameters of a
      subtropical mangrove habitat in the Arabian Gulf (Bahrain) was carried out in
      1993-1994. Six stations at different parts of the tidal channel were selected for
      sampling. The mangrove habitat was found to harbor diverse bacterial communities,
      included among them anoxygenic phototrophs (AP), oxygenic phototrophs (OP),
      organotrophs (OT), total coliforms (TC), faecal coliforms (FC) and
      haloalkaliphiles (HA). Spatial and temporal variations in bacterial communities
      and environmental parameters were found. Each of the OT, AP, TC, and FC were
      dominant in the innermost stations (S1&S2) and gradually decreased seaward. The
      HA community on the other hand, was dominant at the seaward stations (S5&S6) and
      was most likely to have originated from the sea through the tidal flows. Both AP
      and OT were considered as part of the mangrove native flora, whereas TC and FC
      were alien and believed to have been introduced through partially treated sewage
      released at the upstream of the tidal channel. Closely monitoring of the mangrove
      water revealed succession pattern in bacterial communities. The AP community was
      predominant from November 1993 to March 1994, succeeded by dominance of OP from
      June 1994 to October 1994. Both bacterial blooms gave water a pinkish, purple, or
      green color, respectively. Although OT prevailed during Transitional period
      between AP and OP eutrophication, it remained comparatively constant (not less
      than 2 x 10(5)cfu/ml) through other periods. Frequent eutrophication phenomena of
      OP, which took place in summer and autumn, coincided with increases in water
      temperature, chlorophyll a, and nutrients (NO(3)(-) and PO(4)(-)). On the other
      hand, OT and AP were negatively correlated with temperature, salinity and
      chlorophyll a, but no specific pattern was observed in relation to NO(3)(-) and
      PO(4)(-). In comparison with seawater, nutrients such as NO(3)(-) and PO(4)(-)
      were consistently higher in the mangrove habitat. Partially treated sewage and
      farm drainage canals are proposed to form additional sources of nutrients.
      Although, the mangrove habitat has been demonstrated to possess self-cleaning
      properties, data obtained suggest that anthropogenic pollution has a deleterious
      effect.

PMID- 15737358
TI  - Determination of polychlorobiphenyl congeners (PCBs) in the surface water of the
      Venice lagoon.
AB  - The purpose of this study is to evaluate the degree of PCB contamination of
      Venice lagoon water. The PCB determination was made on the filtrate ("dissolved
      PCBs") and on the particulate collected on the filters ("particulate PCBs") by
      continuous liquid-liquid extraction and sonication, respectively, and by HRGC
      LRMS analysis. An estimation of the procedural and "working" blanks was also
      made. Water samples were collected at six sites, selected to represent all the
      pollution situations present in the lagoon, and at a site in the Adriatic Sea.
      The range of the total sum ("dissolved plus particulate") of 49 congener
      concentrations falls between 355 and 1868 pgl(-1); the "dissolved" fraction
      concentrations (250-792 pgl(-1)) are greater at six sites than that of the
      "particulate" fraction (105-1273 pgl(-1)). Chemometric analyses suggest that the
      PCB congener pattern in the Venice Lagoon is different from that in the Adriatic
      Sea.

PMID- 15737357
TI  - Reduction in organic contaminant exposure and resultant hepatic hydropic
      vacuolation in winter flounder (Pseudopleuronectes americanus) following improved
      effluent quality and relocation of the Boston sewage outfall into Massachusetts
      Bay, USA: 1987-2003.
AB  - Effluent upgrades for metropolitan Boston have included toxicant reduction,
      primary and secondary treatment and outfall extension. Between 1992 and 2003
      winter flounder at five stations were surveyed annually for liver and muscle
      burden and chronic hepatic sub-lethal impacts of polynuclear and halogenated
      aromatic hydrocarbons, and metals. Trends in flounder availability and fin
      condition were also examined. In 1988 12% of the adult winter flounder in Boston
      Harbor exhibited hepatic neoplasms and up to 80% had hepatic hydropic vacuolation
      (HV). Tumor prevalence fell to 0-2% and HV to <50% by 1996. Since then tumors
      have been absent, while a steady prevalence of HV has persisted, consistent with
      lower hydrocarbon loading and tissue levels. Contaminants and HV also fell with
      distance from the Boston outfall. After the outfall extension was activated in
      2000, there has been no significant change in flounder liver health at the new
      outfall site.

PMID- 15737359
TI  - Trace element distribution during the reproductive cycle of female and male spiny
      and Pacific scallops, with implications for biomonitoring.
AB  - Trace element concentrations and contents in gills, gonad, kidneys, mantle,
      muscle and remainder during the reproductive cycle of female and male spiny and
      Pacific scallops, from the Strait of Georgia, BC, Canada, were quantified by
      using ICPMS. The elements investigated were chromium, manganese, iron, cobalt,
      nickel, selenium, molybdenum, cadmium, tin and mercury. For all ten elements, the
      tissue distribution was to some extent influenced by species, sex and
      reproductive status. The implications of the present study in relation to the
      design of biomonitoring programmes are: (1) care should be taken to ensure an
      equal/constant sex composition when making interannual comparisons of pooled
      samples. Preferably the sexes should be monitored separately. (2) the practice of
      obtaining pooled samples in the interspawn phase is applicable only to monitoring
      long-term trends in contaminant levels, while the reproductive status should be
      heeded when studying short-term changes. (3) the present study confirms that
      direct temporal or spatial comparisons of absolute accumulated element
      concentrations are only valid intraspecifically.

PMID- 15737360
TI  - Heavy metal contamination in coastal sediments and soils near the Brazilian
      Antarctic Station, King George Island.
AB  - This paper investigates the natural and anthropogenic processes controlling
      sediment chemistry in Admiralty Bay, King George Island, Antarctica, emphasizing
      the area affected by the Brazilian Antarctic Station Comandante Ferraz (Ferraz).
      Total and bioavailable concentrations of sixteen elements were determined in 32
      sediment and 14 soils samples. Factor analysis allowed us to distinguish three
      groups of samples: (1) Ferraz sediments, with higher content of total trace
      metals and organic matter; (2) control sediments, with intermediate
      characteristics; (3) Ferraz soils, with higher bioavailability of most metals due
      to its oxidizing condition and low organic matter content. Major elements such as
      Fe, Al, Ca and Ti presented similar levels in all three groups. Enrichment factor
      calculations showed that paints, sewage and petroleum contamination enhanced
      metal concentrations in Ferraz surface sediments as follows: B, Mo, and Pb
      (>90%); V and Zn (70-80%); Ni, Cu, Mg, and Mn (30-40%). Despite evidence of
      contamination in these sediments, the low bioavailability, probably caused by
      iron-sulfide, indicates small environmental risks.

PMID- 15737362
TI  - Incidence of organochlorine pesticides in muscle and liver tissues of South
      African great white sharks Carcharodon carcharias.

PMID- 15737361
TI  - The distribution and relative toxic potential of organic chemicals in a PCB
      contaminated bay.
AB  - For reliable monitoring of environmental improvement, the PCB contaminated bay
      Orserumsviken on Sweden's Baltic coast was investigated prior to remediation. We
      examined PCB congener patterns and the relative toxic potential of PCBs in
      extracts of three matrices: bottom sediment, settling particulate matter and the
      dissolved phase (obtained from semi-permeable membrane devices). Congener
      patterns were similar in all matrices. Three fractions were isolated from the
      extracts: (1) aliphatic and monocyclic aromatic compounds (MAC-fraction), (2)
      dicyclic aromatic compounds (DAC-fraction), including PCBs, and (3) polycyclic
      aromatic compounds (PAC-fraction), including PAHs. Total extracts and fractions
      were injected into newly fertilised rainbow trout eggs. At larval stage, hepatic
      EROD activities were quantified. Though high, the PCB contamination could explain
      only an estimated 1-5% of the total EROD induction. The order of EROD induction
      potential was: total extract > PAC-fraction > DAC-fraction > MAC-fraction in all
      matrices, suggesting that in Orserumsviken PACs made a larger contribution to the
      EROD induction potential than PCBs and other DACs.

PMID- 15737363
TI  - Comparative paralytic shellfish toxin profiles in the strains of Gymnodinium
      catenatum Graham from the Gulf of California, Mexico.

PMID- 15737364
TI  - A preliminary report of persistent organochlorine pollutants in the Yellow Sea.

PMID- 15737365
TI  - Accumulation of butyltin compounds in benthic biota of the Mersey Estuary.

PMID- 15737368
TI  - Imaging in immunocompetent children who have pneumonia.
AB  - This article discusses the common clinical scenarios regarding otherwise healthy
      children who develop suspected pneumonia in which imaging becomes an issue. The
      following topics are covered concerning the roles of imaging in the management of
      pneumonia: evaluation for possible pneumonia, determination of a specific
      etiologic agent, exclusion of other pathology, evaluation of the child with
      failure of pneumonia to clear, and evaluation of complications related to
      pneumonia.

PMID- 15737366
TI  - Organotin residues and the role of anthropogenic tin sources in the coastal
      marine environment of Indonesia.

PMID- 15737369
TI  - Imaging evaluation of pediatric chest trauma.
AB  - Following a discussion of the various imaging manifestations of pediatric chest
      trauma by anatomic location, the authors discuss their diagnostic approach to the
      pediatric multitrauma patient with an emphasis on chest imaging.

PMID- 15737370
TI  - Imaging of the esophagus in children.
AB  - The main role of the esophagus is to facilitate passage of food from the mouth to
      the stomach. A number of conditions can alter esophageal structure or function
      including congenital anomalies, trauma, infection, and neoplasm. This article
      reviews the anatomy, imaging evaluation, and common problems seen in the
      pediatric thoracic esophagus.

PMID- 15737371
TI  - Imaging evaluation of congenital lung abnormalities in infants and children.
AB  - Congenital lung abnormalities include a wide spectrum of conditions and are an
      important cause of morbidity and mortality in infants and children. This article
      discusses focal lung abnormalities and the dysmorphic lung. Pulmonary
      arteriovenous malformations have been included at the end of the article.
      Anomalies affecting the pulmonary parenchyma, its arterial supply, and venous
      drainage are thus discussed.

PMID- 15737372
TI  - Imaging evaluation of pediatric mediastinal masses.
AB  - Mediastinal masses in children are a heterogeneous group of asymptomatic to
      potentially life-threatening congenital, infectious, or neoplastic lesions that
      can present complex diagnostic and therapeutic dilemmas. This article presents
      the imaging features of the common mediastinal masses seen in the pediatric
      population. Classification of the masses is performed according to the
      traditional mediastinal compartment model, consisting of the anterior, middle,
      and posterior mediastinum. This scheme facilitates differentiation of the variety
      of disorders.

PMID- 15737373
TI  - Imaging evaluation of chest wall disorders in children.
AB  - This article discusses the imaging evaluation of chest wall disorders in
      children.

PMID- 15737374
TI  - Imaging evolution of airway disorders in children.
AB  - This article discusses and illustrates the insights gained from CT imaging of the
      lungs in infants and young children who do not have respiratory motion and at end
      inspiratory and resting end-expiratory lung volumes using noninvasive controlled
      ventilation CT technique. The potential role of noninvasive controlled
      ventilation CT in developing quantitative measures of airway disease is
      highlighted and clinical examples demonstrating the use of the technique are
      shown.

PMID- 15737375
TI  - Imaging considerations: interstitial lung disease in children.
AB  - This article provides a guide for the technique and interpretation of high
      resolution chest CT of diffuse lung disease in children. Specific causes of
      diffuse lung disease in infants and children are reviewed as a guide to the
      interpretation of these images. New information, particularly the identification
      of surfactant protein mutations, is included. The idiopathic interstitial
      pneumonia classification, which is frequently applied to pediatric lung biopsy
      specimens, is also discussed.

PMID- 15737376
TI  - Pediatric chest ultrasound.
AB  - Ultrasound examination of the thorax can be quite rewarding in children, because
      their unique thoracic anatomy provides many acoustic windows into the chest. With
      only a modest effort, chest ultrasonography can provide many clinically relevant
      answers, without the radiation exposure from CT, or the need for sedation
      sometimes required for CT and MR imaging.

PMID- 15737377
TI  - Technique of pediatric thoracic CT angiography.
AB  - CT angiography is now an accepted application of contemporary multidetector row
      CT. Faster scanning, thinner slices, and improvement in intravenous contrast
      enhancement are benefits that have offered unique opportunities for pediatric
      thoracic angiographic evaluation, and often obviate routine angiography.
      Pediatric CT angiography can be challenging but adherence to a relatively
      straightforward step-by-step method, emphasizing patient preparation and
      technical familiarity, can result in excellent examinations even in the smallest
      infants and most complex clinical scenarios.

PMID- 15737378
TI  - Thoracic disorders in the immunocompromised child.
AB  - Immunodeficiencies in children may be caused by primary immunodeficiency
      syndromes or can result from secondary disorders of immune regulation. Thoracic
      complications in immunocompromised children are frequent and may vary according
      to the type of the immunodeficiency. Imaging plays a pivotal role in detection
      and distinction of the variety of sequelae. It is important for the radiologist
      to understand both the spectrum of pediatric immune disorders, and the mechanisms
      underlying these disorders.

PMID- 15737379
TI  - Trapping of microparticles in the near field of an ultrasonic transducer.
AB  - We are investigating means of handling microparticles in microfluidic systems, in
      particular localized acoustic trapping of microparticles in a flow-through
      device. Standing ultrasonic waves were generated across a microfluidic channel by
      ultrasonic microtransducers integrated in one of the channel walls. Particles in
      a fluid passing a transducer were drawn to pressure minima in the acoustic field,
      thereby being trapped and confined at the lateral position of the transducer. The
      spatial distribution of trapped particles was evaluated and compared with
      calculated acoustic intensity distributions. The particle trapping was found to
      be strongly affected by near field pressure variations due to diffraction effects
      associated with the finite sized transducer element. Since laterally confining
      radiation forces are proportional to gradients in the acoustic energy density,
      these near field pressure variations may be used to get strong trapping forces,
      thus increasing the lateral trapping efficiency of the device. In the
      experiments, particles were successfully trapped in linear fluid flow rates up to
      1mm/s. It is anticipated that acoustic trapping using integrated transducers can
      be exploited in miniaturised total chemical analysis systems (microTAS), where
      e.g. microbeads with immobilised antibodies can be trapped in arrays and
      subjected to minute amounts of sample followed by a reaction, detected using
      fluorescence.

PMID- 15737381
TI  - A comparison measurement of nonlinear ultrasonic waves in tubes by a microphone
      and by an optical interferometric probe.
AB  - This paper deals with the analysis of ultrasonic fields inside waveguides
      generated by ultrasonic waves of high amplitude. These waves behave nonlinearly,
      so it is not possible to use standard linear equations to describe their
      behaviour. Therefore, we started with an experimental determination of the
      acoustic pressure of air in glass tubes. We chose two methods of measurement--by
      a microphone and by an optical interferometric probe. The conventional method by
      a microphone creates numerous problems, which can be avoided by using an optical
      method, a heterodyne laser interferometer.

PMID- 15737380
TI  - In vitro chronic hepatic disease characterization with a multiparametric
      ultrasonic approach.
AB  - Although, high resolution, real-time ultrasonic (US) imaging is routinely
      available, image interpretation is based on grey-level and texture and
      quantitative evaluation is limited. Other potentially useful diagnostic
      information from US echoes may include modifications in tissue acoustic
      parameters (speed, attenuation and backscattering) resulting from disease
      development. Changes in acoustical parameters can be detected using time-of
      flight and spectral analysis techniques. The objective of this study is to
      explore the potential of three parameters together (attenuation coefficient, US
      speed and integrated backscatter coefficient-IBC) to discriminate healthy and
      fibrosis subgroups in liver tissue. Echoes from 21 fresh in vitro samples of
      human liver and from a plane reflector were obtained using a 20-MHz central
      frequency transducer (6-30 MHz bandpass). The scan plane was parallel to the
      reflector placed beneath the liver. A 30 x 20 matrix of A-scans was obtained,
      with a 200-microm step. The samples were classified according to the Metavir
      scale in five different degrees of fibrosis. US speed, attenuation and IBC were
      estimated from standard methods described in the literature. Statistical tests
      were applied to the results of each parameter individually and indicated that it
      was not possible to identify all the fibrosis groups. Then a discriminant
      analysis was performed for the three parameters together resulting in a
      reasonable separation of fibrotic groups. Although the number of tissue samples
      is limited, this study opens the possibility of enhancing the discriminant
      capability of ultrasonic parameters of liver tissue disease when they are
      combined together.

PMID- 15737382
TI  - A finite-element model of the aperture method for determining the effective
      radiating area of physiotherapy treatment heads.
AB  - This paper describes a theoretical study of the way in which a circular aperture
      placed in front of a plane-piston modifies the ultrasonic field it generates.
      Specifically, the radiated acoustic power transmitted by the aperture and the
      radiation force experienced by an absorbing target placed in the transmitted
      beam, are evaluated at a distance from the exit-side of the aperture. The
      calculations used a finite element (FE) method, in conjunction with a surface
      Helmholtz integral formulation to solve the fluid/structure interaction problem.
      The PAFEC (Program for Automatic Finite Element Computation) vibroacoustics
      software was used for the FE calculations and the implementation of the surface
      Helmholtz integral formulation method. Acoustic pressures and particle velocities
      were computed at required points, whilst accounting for the presence of the
      aperture in the medium, together with its dynamic properties when subjected to an
      incident sound field. This enabled the calculation of the radiation force on the
      absorber and its variation with the applied aperture diameter was investigated.
      As part of the validation process for the new FE aperture model, the ratio of
      radiation force to radiated acoustic power obtained using the FE method in the
      unapertured case, through the use of the Rayleigh integral, yielded good
      agreement with results obtained through an analytical solution. The study has
      been carried out to provide a better understanding of the factors affecting the
      measurement uncertainty for the aperture method of determining the effective
      radiating area (A(ER)) of physiotherapy ultrasound treatment heads.

PMID- 15737383
TI  - A theoretical model describing the transfer characteristics of a membrane
      hydrophone and validation.
AB  - This paper presents a theoretical model describing the transfer characteristics
      of a bilaminar polyvinylidene fluoride membrane hydrophone. The model applied
      uses a matrix formulation for one-dimensional propagation in multi-layered media.
      Arbitrary interconnections of piezoelectric layers are possible. The electrical
      transfer characteristics of the hydrophone leg and cable are modelled as
      transmission lines using a two-port network approach. The model is validated
      against measured open-circuit sensitivities for a 25 microm film thickness 0.5 mm
      active element diameter bilaminar hydrophone (50 microm total film thickness).
      Good agreement between theory and experiment is demonstrated. A 9 microm film
      thickness 0.5 mm active element diameter bilaminar hydrophone (18 microm total
      film thickness) together with amplifier is also modelled. The voltage at the
      output stage of the amplifier is measured and, by knowledge of the transfer
      characteristics of the complete system, the pressure waveform at the hydrophone
      position is estimated and compared with the acoustic pressure waveform derived
      using a laser interferometer. Good agreement is obtained.

PMID- 15737384
TI  - Acoustic emission transducers--development of a facility for traceable out-of
      plane displacement calibration.
AB  - Acoustic emission (AE) is a widely used technique that has been employed for the
      integrity testing of a range of vessels and structures for many years. The last
      decade has seen advances in signal processing, such that the reliability of AE
      technology is now being recognised by a wider range of industries. Furthermore,
      the need for quality control at the manufacturing stage, and requirements of in
      service testing, is encouraging the issue of traceable measurements to be
      addressed. Currently, no independent calibration service for acoustic emission
      transducers is available within Europe. The UKs National Physical Laboratory
      (NPL) is undertaking work to develop a measurement facility for the traceable
      calibration of AE sensors. Such calibrations can contribute to greater acceptance
      of AE techniques in general, by meeting quality system and other traceability
      requirements. In this paper the key issues surrounding the development of such a
      facility are reviewed, including the need to establish repeatable AE sources,
      select suitable test blocks and to understand the limitations imposed by AE
      sensors themselves. To provide an absolute measurement of the displacement on the
      surface of a test block, laser interferometry is employed. In this way the output
      voltage of an AE sensor can be directly related to the displacement detected at
      the block surface. A possible calibration methodology is discussed and
      preliminary calibration results are presented for a commercially available AE
      sensor, showing its response to longitudinal wave modes.

PMID- 15737385
TI  - A comparison of HIFU-induced lesion size measurement based on gross histological
      examination and image of bovine thigh in vitro.
AB  - The aim of this study was to investigate the agreement in HIFU-induced lesion
      sizes between measurements based on gross histological examination and those from
      images. Experiments were conducted in an experimental arrangement with a three
      way multiscan ultrasonic inspection system and imaging was done by B-mode
      ultrasound (US). Bovine thigh muscle with and without fascia lata was treated
      with an in situ spatially averaged focal intensity ranging between 750 W cm(-2)
      and 1565 W cm(-2) and sonication-time was variable from 8 to 20s. Assessment of
      the two measurement methods showed a rather weak correlation in the samples
      without fascia lata. For clarity and convenience in the discussion, sample
      muscles with and without fascia lata were labeled F and M, respectively. It was
      difficult to measure the lesion size from ultrasonographic images of F samples,
      so there was disagreement in the samples with fascia lata. This investigation
      showed that the presence of fascia lata in bovine thigh muscle has the likely
      effect of affecting the ultrasound image and makes it difficult to distinguish
      coagulated tissue from surrounding healthy tissue. There was no significant
      correlation between ultrasonography and the gross histological findings in M
      samples. Data supported that at for an in situ spatially averaged focal intensity
      ranging between 750 W cm(-2) and 1565 W cm(-2) and relatively shorter exposures
      (sonication-time variable from 1 to 8s) higher correlation between image and
      gross histology measurement was found in excised bovine muscle specimens.

PMID- 15737386
TI  - Parameter measurement of the cylindrically curved thin layer using low-frequency
      circumferential Lamb waves.
AB  - The characteristic parameters of a cylindrically curved thin layer include its
      elastic constants, thickness and curved radius. A layer is considered thin if the
      echoes from the front and back surfaces of the layer cannot be separated in the
      time domain, and/or that the wave arrivals corresponding to longitudinal and
      shear wave part cannot be identified in the time or space domain. This paper
      describes a low-frequency circumferential Lamb wave method to characterize those
      parameters of a cylindrically curved thin layer. The technique is based on the
      measurement of circumferential Lamb wave phase velocity and the unknown parameter
      is estimated through minimizing the mean square error obtained by comparing
      theoretical and experimental phase velocities. The sensitivity and accuracy of
      the proposed technique to different parameters are analyzed. Using the present
      technique, a cylindrically curved thin layer with thickness down to ten percent
      of the longitudinal wavelength can be successfully measured with an average
      relative error less than two-percent in our experiment.

PMID- 15737387
TI  - Load characteristics of high power sandwich piezoelectric ultrasonic transducers.
AB  - Based on the equivalent circuit theory, the load characteristics of high power
      piezoelectric ultrasonic sandwich transducers are studied. Two types of loads are
      studied. One is liquid load as in ultrasonic cleaning, and the other is solid
      load as in ultrasonic drilling and machining. The effect of load and structure of
      the transducer on the resonance frequency of the transducer is analyzed. It is
      shown that the effect of load on the resonance frequency of sandwich transducers
      with different structures is different. For liquid load as in ultrasonic
      cleaning, the effect of the load on the resonance frequency of the sandwich
      transducer with symmetrical structure is the largest. It is the smallest for the
      transducer with its displacement node in the back metal cylinder. For solid load
      as in ultrasonic drilling and machining, the effect of the load on the resonance
      frequency of the sandwich transducer with its displacement node in the front
      metal cylinder is the largest. It is also the smallest for the transducer with
      its displacement node in the back metal cylinder. On the other hand, for some
      applications, such as ultrasonic drilling, when the lateral dimension of the tool
      is much less than that of the transducer, its effect on the resonance frequency
      of the transducer is small. The conclusions are useful in designing vibrating
      systems for different ultrasonic applications.

PMID- 15737388
TI  - Estimation of ultrasound attenuation and dispersion using short time Fourier
      transform.
AB  - Determination of the acoustic attenuation and dispersion has important
      applications in ultrasound tissue characterization and non-destructive material
      testing. Current signal processing methods Fourier transform of ultrasound
      signals to get the spectra of amplitude and phase to estimate respectively the
      attenuation and dispersion of a given medium. These methods are frequency domain
      method and obsessed with ambiguity issue in the phase unwrapping calculation.
      Conventional ultrasound velocity measuring method detects the time of arrival of
      a pulse (or echo) signal, which is a time domain method to compute group velocity
      (not phase velocity). This paper presents a novel approach based on the short
      time Fourier transform (STFT)--a time-frequency analysis, to estimate the
      ultrasonic dispersion and attenuation. Only the amplitude information of the
      pulse-signal spectra is used. Based on the time-frequency presentation, the
      attenuation coefficient of the signal is obtained by computing the amplitude
      decay of pulse spectrum in time domain, while phase velocities are obtained based
      on the "time-of-flight" (TOF) of the mono frequency component of the pulse
      signals. As a result, we eliminate the ambiguity issue in phase angle
      calculation. Furthermore, the proposed method makes the phase velocity
      pedagogically intuitive for novice users. The paper presents experiments to
      evaluate demonstrate the performance of the proposed method.

PMID- 15737390
TI  - Design of ultrasonic wedge transducer.
AB  - Cones and wedges inserted between an ultrasonic transducer and the specimen
      provide the transducer (circular or rectangular shape) with enhanced capability
      for point or line contact with the specimen. Such an arrangement is useful in
      that the transducer can be used for transmitting to and receiving from a point
      (or line) source, and that it can eliminate the undesirable aperture effect that
      makes the transducer blind to waves traveling in certain directions and those of
      certain frequencies. In this paper, a comprehensive numerical analysis based on a
      wave propagation model is carried out for the study of characteristics and
      parameters of cones and wedges influencing their performance. We study the effect
      of the dimensions, shape and aperture on the frequency response and the angle of
      incidence of the wave. For computational accuracy and efficiency, the boundary
      element method is used in the analysis.

PMID- 15737389
TI  - Electro-acoustical characterization procedure for cMUTs.
AB  - A procedure for the electro-acoustical characterization in air of cMUTs is
      reported. First, the measured input electrical impedance of the transducer is
      used to calculate the transducer parameters at different bias voltages by fitting
      it with the Mason model. Then, the single membrane equivalent circuit can be
      calculated. Second, the cMUT impulse response is obtained through a send-and
      receive experiment to be compared with the one predicted by the Mason model. In
      order to minimize the influence of the emitter in the obtained impulse response
      an ad hoc broadband piezoelectric transducer centered at the resonant frequency
      of the cMUT was fabricated. Using this transducer, no deconvolution of the
      impulse response of the emitter in the cMUT reception pulse is necessary. The
      procedure is tested for two cMUTs with silicon-rich nitride as structural layer
      and different membrane diameters (60 and 70 microm).

PMID- 15737391
TI  - Africa's wild C4 plant foods and possible early hominid diets.
AB  - A small minority of Africa's wild plant foods are C4. These are primarily the
      seeds of some of the C4 grasses, the rootstocks and stem/leaf bases of some of
      the C4 sedges (especially papyrus), and the leaves of some of the C4 herbaceous
      dicots (forbs). These wild food plants are commonly found in disturbed ground and
      wetlands (particularly the grasses and sedges). Multiple lines of evidence
      indicate that C4 grasses were present in Africa by at least the late Miocene. It
      is a reasonable hypothesis that the prehistory of the C4 sedges parallels that of
      the C4 grasses, but the C4 forbs may not have become common until the late
      Pleistocene. CAM plants may have a more ancient history, but offer few
      opportunities for an additional C4-like dietary signal. The environmental
      reconstructions available for the early South African hominid sites do not
      indicate the presence of large wetlands, and therefore probably the absence of a
      strong potential for a C4 plant food diet. However, carbon isotope analyses of
      tooth enamel from three species of early South African hominids have shown that
      there was a significant but not dominant contribution of C4 biomass in their
      diets. Since it appears unlikely that this C4 component could have come
      predominantly from C4 plant foods, a broad range of potential animal contributors
      is briefly considered, namely invertebrates, reptiles, birds, and small mammals.
      It is concluded that the similar average C4 dietary intake seen in the three
      South African hominid species could have been acquired by differing contributions
      from the various sources, without the need to assume scavenging or hunting of
      medium to large grazing ungulates. Effectively similar dominantly dryland paleo
      environments may also be part of the explanation. Theoretically, elsewhere in
      southern and eastern Africa, large wetlands would have offered early hominids
      greater opportunities for a C4 plant diet.

PMID- 15737393
TI  - Intrasexual selection in Verreaux's sifaka (Propithecus verreauxi verreauxi).
AB  - Studies of sexual selection show that both female choice and male-male
      competition can influence the evolution and expression of male phenotypes. In
      this regard, it is important to determine the functional basis through which male
      traits influence variation in male reproductive success. In this study, we
      estimate the strength and type of sexual selection acting on adult males in a
      population of wild lemur, Verreaux's sifaka (Propithecus verreauxi verreauxi).
      The data used in this study were collected at Beza Mahafaly Special Reserve,
      southwest Madagascar. We conducted paternity analyses on 70 males in order to
      estimate the distribution of reproductive success in this population. Paternity
      data were combined with morphometric data in order to determine which
      morphological traits covary with male fitness. Five morphological traits were
      defined in this analysis: body size, canine size, torso shape, arm shape, and leg
      shape. We utilized phenotypic selection models in order to determine the strength
      and type of selection acting directly on each trait. Our results show that
      directional selection acts on leg shape (a trait that is functionally related to
      locomotor performance), stabilizing selection acts on body mass and torso shape,
      and negative correlational selection acts on body mass and leg shape. We draw
      from biomechanical and kinematic studies of sifaka locomotion to provide a
      functional context for how these traits influence male mating competition within
      an arboreal environment. Verreaux's sifaka and many other gregarious lemurs are
      sexually monomorphic in body mass and canine size, despite a high frequency and
      intensity of male-male aggressive competition. Our results provide some insight
      into this paradox: in our population, there is no directional selection acting on
      body mass or canine size in males. The total pattern of selection implicates that
      behaviors relating to locomotor performance are more important than behaviors
      relating to fighting ability during intrasexual contests.

PMID- 15737392
TI  - Catarrhine primate divergence dates estimated from complete mitochondrial
      genomes: concordance with fossil and nuclear DNA evidence.
AB  - Accurate divergence date estimates improve scenarios of primate evolutionary
      history and aid in interpretation of the natural history of disease-causing
      agents. While molecule-based estimates of divergence dates of taxa within the
      superfamily Hominoidea (apes and humans) are common in the literature, few such
      estimates are available for the Cercopithecoidea (Old World monkeys), the sister
      taxon of the hominoids in the primate infraorder Catarrhini. To help fill this
      gap, we have sequenced the entire mitochondrial DNA (mtDNA) genomes from a
      representative of three cercopithecoid tribes, Cercopithecini (Chlorocebus
      aethiops), Colobini (Colobus guereza), and Presbytini (Trachypithecus obscurus),
      and analyzed these new data together with other catarrhine mtDNA genomes
      available in public databases. Molecular divergence date estimates are dependent
      on calibration points gleaned from the paleontological record. We defined
      criteria for the selection of good calibration points and identified three points
      meeting these criteria: Homo-Pan, 6.0 Ma; Pongo-hominines, 14.0 Ma;
      hominoid/cercopithecoid, 23.0 Ma. Because a uniform molecular clock does not fit
      the catarrhine mtDNA data, we estimated divergence dates using a penalized
      likelihood and a Bayesian method, both of which take into account the effects of
      rate differences on lineages, phylogenetic tree structure, and multiple
      calibration points. The penalized likelihood method applied to the coding regions
      of the mtDNA genome yielded the following divergence date estimates, with
      approximate 95% confidence intervals: cercopithecine-colobine, 16.2 (14.4-17.9)
      Ma; colobin-presbytin, 10.9 (9.6-12.3) Ma; cercopithecin-papionin, 11.6 (10.3
      12.9) Ma; and Macaca-Papio, 9.8 (8.6-10.9) Ma. Within the hominoids, the
      following dates were inferred: hylobatid-hominid, 16.8 (15.0-18.5) Ma; Gorilla
      Homo+Pan, 8.1 (7.1-9.0) Ma; Pongo pygmaeus pygmaeus-P. p. abelii, 4.1 (3.5-4.7)
      Ma; and Pan troglodytes-P. paniscus, 2.4 (2.0-2.7) Ma. These dates were similar
      to those found using penalized likelihood on other subsets of the data, but
      slightly younger than several of the Bayesian estimates.

PMID- 15737394
TI  - Evidence of hunting and hafting during the Middle Stone Age at Sibidu Cave,
      KwaZulu-Natal, South Africa: a multianalytical approach.
AB  - Points and point fragments from Middle Stone Age layers (dated to between 50,000
      and 60,000 years ago) from Sibudu Cave, KwaZulu-Natal, South Africa, were
      examined to establish whether they were used as hafted spearheads for hunting. A
      multi-analytical approach was followed, using macrofracture analysis, use-wear
      analysis, and residue analysis. In addition to the analytical processes, an
      experimental project tested the results of the macrofracture analysis on local
      raw materials. The study shows that points from Sibudu Cave were indeed hafted
      and used as hunting tools. It was further established that plant twine was
      probably the preferred binding material to attach the points to wooden hafts.
      Resin may have been used as an adhesive in combination with the binding material.
      A detailed examination of the ochre distribution on the points confirmed that
      ochre was also part of the hafting arrangement. The need to use a dependable
      methodology for the recognition of hunting and hafting traces on stone points
      from the southern African Middle Stone Age context is briefly discussed.

PMID- 15737395
TI  - Hominins, sedges, and termites: new carbon isotope data from the Sterkfontein
      valley and Kruger National Park.
AB  - Stable carbon isotope analyses have shown that South African australopiths did
      not have exclusively frugivorous diets, but also consumed significant quantities
      of C4 foods such as grasses, sedges, or animals that ate these foods. Yet, these
      studies have had significant limitations. For example, hominin sample sizes were
      relatively small, leading some to question the veracity of the claim for
      australopith C4 consumption. In addition, it has been difficult to determine
      which C4 resources were actually utilized, which is at least partially due to a
      lack of stable isotope data on some purported australopith foods. Here we begin
      to address these lacunae by presenting carbon isotope data for 14 new hominin
      specimens, as well as for two potential C4 foods (termites and sedges). The new
      data confirm that non-C3 foods were heavily utilized by australopiths, making up
      about 40% and 35% of Australopithecus and Paranthropus diets respectively. Most
      termites in the savanna-woodland biome of the Kruger National Park, South Africa,
      have intermediate carbon isotope compositions indicating mixed C3/C4 diets. Only
      28% of the sedges in Kruger were C4, and few if any had well-developed rhizomes
      and tubers that make some sedges attractive foods. We conclude that although
      termites and sedges might have contributed to the C4 signal in South African
      australopiths, other C4 foods were also important. Lastly, we suggest that the
      consumption of C4 foods is a fundamental hominin trait that, along with
      bipedalism, allowed australopiths to pioneer increasingly open and seasonal
      environments.

PMID- 15737396
TI  - Sexual dimorphism in Australopithecus afarensis revisited: how strong is the case
      for a human-like pattern of dimorphism?

PMID- 15737397
TI  - Control of replication in I-complex plasmids.
AB  - The closely related plasmids that make up the I-complex group and the more
      distantly related IncL/M plasmids regulate the frequency of initiation of their
      replication by controlling the efficiency of translation of the rate limiting
      replication initiator protein, RepA. Translation initiation of repA is dependent
      on the formation of a pseudoknot immediately upstream of its Shine-Dalgarno
      sequence. Formation of this pseudoknot involves base pairing between two
      complementary sequences in the repA mRNA and requires that the secondary
      structure sequestering the distal sequence be disrupted by movement of the
      ribosome translating and terminating a leader peptide, whose coding sequence
      precedes and overlaps that of repA. Expression of repA is controlled by a small
      antisense RNA, RNAI, which on binding to its complementary target in the repA
      mRNA not only pre-empts formation of the pseudoknot, but also inhibits
      translation of the leader peptide. The requirement that translation of the leader
      peptide be completed for the pseudoknot to form increases the time available for
      the inhibitory interaction of RNAI with its target, so that at high copy number
      the frequency of pseudoknot formation is lowered, reducing the proportion of repA
      mRNA that are translated. At low copy number, when concentration of RNAI is low,
      repA is translated with increased frequency, leading to increased frequency of
      plasmid replication.

PMID- 15737398
TI  - Elements in the co-evolution of relaxases and their origins of transfer.
AB  - The central elements in the conjugative mobilization of most plasmids are the
      relaxase and its cognate origin of transfer (oriT). The relaxase of the plasmid
      R1162, together with its oriT, belong to a large and widely distributed family of
      related relaxase/oriT pairs. Several of the properties of these elements are
      considered for R1162 and for other members of this family with a view to
      understanding how systems for mobilization might have evolved.

PMID- 15737399
TI  - Partition-mediated plasmid pairing.
AB  - Plasmid partition systems are essential for the stability and thus the survival
      of low-copy-number plasmids in growing bacterial populations. The partition
      reaction is responsible for proper intracellular distribution of plasmids in the
      bacterial cell cycle. One common step in most partition models is the pairing of
      plasmids to each other by partition components. Here, evidence that supports the
      pairing of plasmids via their partition complexes is reviewed, and discussed in
      light of recent observations that many plasmids, including those without active
      partition systems are clustered in limited groups inside bacterial cells.

PMID- 15737400
TI  - Plasmid rolling-circle replication: highlights of two decades of research.
AB  - This review provides a historical perspective of the major findings that
      contributed to our current understanding of plasmid rolling-circle (RC)
      replication. Rolling-circle-replicating (RCR) plasmids were discovered
      approximately 20 years ago. The first of the RCR plasmids to be identified were
      native to Gram-positive bacteria, but later such plasmids were also identified in
      Gram-negative bacteria and in archaea. Further studies revealed mechanistic
      similarities in the replication of RCR plasmids and the single-stranded DNA
      bacteriophages of Escherichia coli, although there were important differences as
      well. Three important elements, a gene encoding the initiator protein, the double
      strand origin, and the single strand origin, are contained in all RCR plasmids.
      The initiator proteins typically contain a domain involved in their sequence
      specific binding to the double strand origin and a domain that nicks within the
      double strand origin and generates the primer for DNA replication. The double
      strand origins include the start-site of leading strand synthesis and contain
      sequences that are bound and nicked by the initiator proteins. The single strand
      origins are required for synthesis of the lagging strand of RCR plasmids. The
      single strand origins are non-coding regions that are strand-specific, and
      contain extensive secondary structures. This minireview will highlight the major
      findings in the study of plasmid RC replication over the past twenty years.
      Regulation of replication of RCR plasmids will not be included since it is the
      subject of another review.

PMID- 15737401
TI  - The evolution of pTF-FC2 and pTC-F14, two related plasmids of the IncQ-family.
AB  - Two plasmids, pTF-FC2 and pTC-F14, that belong to the IncQ-like plasmid family
      were isolated from two related bacteria, Acidithiobacillus ferrooxidans and
      Acidithiobacillus caldus, respectively. The backbone regions of the two plasmids
      share a sufficiently high amount of homology to indicate that they must have
      originated from the same ancestral plasmid. Although some of their replication
      proteins could complement each other, the plasmids have evolved sufficiently for
      their replicons to have become compatible. This compatibility has occurred by
      changes in the iteron sequence, RepC (iteron binding protein) specificity and the
      regulation properties of the RepB primase. Two of the five mobilization genes
      have remained highly conserved, whereas the other three genes appear to have
      evolved such that each plasmid is mobilized most efficiently by a different self
      transmissible plasmid. Plasmids pTF-FC2 and pTC-F14 do not appear to compete at
      the level of mobilization. The antitoxins of the toxin-antitoxin (TA) plasmid
      stability systems were partly able to neutralize the toxins of the other plasmid
      and also to partly cross-regulate the TA systems of the other plasmid with the
      antitoxin of pTF-FC2 being the most effective cross-regulator. Other aspects of
      the evolution of the two plasmids are described and the danger of making the
      assumption that incompatibly of IncQ-like plasmids is a reflection of the degree
      of relatedness of two plasmids is discussed.

PMID- 15737402
TI  - Limited use of the Cre/loxP recombination system in efficient production of loxP
      containing minicircles in vivo.
AB  - The Cre/loxP recombination system of bacteriophage P1 is one of the most powerful
      tools in genome engineering. We report, however, that the activity of the
      Cre/loxP system interferes with the stability of the multicopy loxP-bearing
      plasmids in Escherichia coli recA bacteria. Due to the predominantly
      unidirectional Cre-mediated high-order multimer formation of these plasmids, the
      number of their copies (overall yield) gradually decreases. Intermolecular
      recombination reduces the copy number of plasmids and eventually increases their
      segregational instability. We have found that in the presence of even the
      slightest amount of Cre activity, loxP-bearing plasmids continuously undergo
      multimerization, which very rapidly leads to loxP-plasmid free cells. Our results
      are compatible with the hypothesis of the multimer catastrophe [Cell, 1984 (36),
      1097].

PMID- 15737403
TI  - Description of complete DNA sequence of two plasmids from the nukacin ISK-1
      producer, Staphylococcus warneri ISK-1.
AB  - We report the whole DNA sequence of two plasmids, pPI-1 (30.2 kb) and pPI-2 (2.8
      kb). These plasmids are from Staphylococcus warneri ISK-1, which produces a
      lantibiotic, nukacin ISK-1. Curing of pPI-1 resulted in a loss of bactericidal
      activity in the culture supernatant and the host's immunity to nukacin ISK-1,
      suggesting that the biosynthetic genes of the bacteriocin are encoded by pPI-1.
      Based on the results of a homology search of each open reading flame, pPI-1 is
      comprised of the following four distinct regions: (1) the nukacin ISK-1
      biosynthesis and immunity gene cluster, (2) the thioredoxin gene cluster, (3) the
      replication region, and (4) a region of Staphylococcus epidermidis ATCC 12228,
      highly homologous to pSE-12228-05. Gene organization in the nukacin ISK-1
      biosynthesis and immunity gene cluster is different from that in other lacticin
      481 type gene clusters. The features of the replication protein encoded in the
      replicating region are somewhat different from other staphylococcus theta
      replicating plasmids. pPI-2 comprised a disinfectant resistant gene, qacC, and
      the whole DNA sequence showed significant similarity to those of other qacC
      plasmids such as pSK108, suggesting that pPI-2 belongs to the qacC plasmid group.

PMID- 15737404
TI  - Cryptic plasmid pSKU146 from the wall-less plant pathogen Spiroplasma kunkelii
      encodes an adhesin and components of a type IV translocation-related conjugation
      system.
AB  - A cryptic plasmid of the wall-less plant pathogenic mollicute, Spiroplasma
      kunkelii CR2-3X, was cloned and its sequence analyzed. The 14,615 bp plasmid,
      designated pSKU146, has a nucleotide content of 28 mol% G + C, and contains 18
      potential protein-coding regions (open reading frames, ORFs), of which six encode
      proteins that exhibit similarity to virulence-associated proteins involved in
      cell-to-cell adhesion or conjugal DNA transfer. One ORF encodes a 96 kDa protein,
      SkARP1, that is highly similar to SARP1 adhesin involved in attachment of
      Spiroplasma citri to insect vector gut membrane. Five ORFs encode proteins
      similar to TraE and Mob in walled bacteria, and to ORFs found in the integrative,
      conjugative element (ICEF) of Mycoplasma fermentans, respectively. Presence of
      domains similar to proteins of the Type IV secretion system in pathogenic
      bacteria suggests that spiroplasma possesses a related translocation system.
      Plasmid pSKU146 also contains two identical oriT regions each containing a nick
      sequence characteristic of the IncP conjugative plasmid family, as well as a 58
      bp palindromic sequence, palSK1. Features in pSKU146 suggest that the plasmid
      functions as a mobile genetic element in conjugative transmission of spiroplasma
      pathogenicity-related genes.

PMID- 15737405
TI  - Gene therapy targeted at calcium handling as an approach to the treatment of
      heart failure.
AB  - Chronic congestive heart failure primarily of ischemic origin remains a leading
      cause of morbidity and mortality in the United States and other leading
      countries. The current main stream of therapy is, however, palliative and uses a
      complex regimen of drugs, the actions of which are not understood completely. On
      the other hand, unfavorable remodeling after cardiac injuries of multiple causes
      has been thought to lead to cardiac contractile dysfunction in heart failure, and
      a body of scientific evidence points to a central role of intrinsic defects in
      intracellular calcium handling in cardiomyocytes that arise from the distorted
      functions of several key regulatory molecules on plasma membrane or sarcoplasmic
      reticulum (SR), a muscle-specific intracellular membrane complex that stores
      calcium at high concentration. Accordingly, the initial appetite to use gene
      transfer strategies to modulate calcium regulatory proteins was to validate
      molecular targets for the development of new pharmaceuticals; however, remarkable
      therapeutic efficacies found in an initial series of studies using various heart
      failure animal models immediately promoted us to seek ways to directly apply gene
      transfer to cure clinical heart failure. The first part of this article reviews
      our up-to-date knowledge of various functional components to regulate calcium
      handling in cardiomyocytes, including beta-adrenergic receptor, L-type calcium
      channel, ryanodine receptor (RyR) and its associated proteins, sarco-endoplasmic
      reticulum calcium ATPase (SERCA), and phospholamban (PLN), and their
      abnormalities in failing hearts. A series of new somatic gene transfer attempts
      targeting calcium handling in cardiomyocytes are discussed thereafter.

PMID- 15737407
TI  - Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's
      disease.
AB  - In the pursuit of improved treatments for Parkinson's disease (PD), the adenosine
      A(2A) receptor has emerged as an attractive nondopaminergic target. Based on the
      compelling behavioral pharmacology and selective basal ganglia expression of this
      G-protein-coupled receptor, its antagonists are now crossing the threshold of
      clinical development as adjunctive symptomatic treatment for relatively advanced
      PD. The antiparkinsonian potential of A(2A) antagonism has been boosted further
      by recent preclinical evidence that A(2A) antagonists might favorably alter the
      course as well as the symptoms of the disease. Convergent epidemiological and
      laboratory data have suggested that A(2A) blockade may confer neuroprotection
      against the underlying dopaminergic neuron degeneration. In addition, rodent and
      nonhuman primate studies have raised the possibility that A(2A) receptor
      activation contributes to the pathophysiology of dyskinesias-problematic motor
      complications of standard PD therapy--and that A(2A) antagonism might help
      prevent them. Realistically, despite being targeted to basal ganglia
      pathophysiology, A(2A) antagonists may be expected to have other beneficial and
      adverse effects elsewhere in the central nervous system (e.g., on mood and sleep)
      and in the periphery (e.g., on immune and inflammatory processes). The thoughtful
      design of new clinical trials of A(2A) antagonists should take into consideration
      these counterbalancing hopes and concerns and may do well to shift toward a
      broader set of disease-modifying as well as symptomatic indications in early PD.

PMID- 15737408
TI  - The role of alpha-synuclein in neurodegenerative diseases.
AB  - Alpha-synuclein is a 140 amino acid neuronal protein that has been associated
      with several neurodegenerative diseases. A point mutation in the gene coding for
      the alpha-synuclein protein was the first discovery linking this protein to a
      rare familial form of Parkinson's disease (PD). Subsequently, other mutations in
      the alpha-synuclein gene have been identified in familial PD. The aggregated
      proteinaceous inclusions called Lewy bodies found in PD and cortical Lewy body
      dementia (LBD) were discovered to be predominantly alpha-synuclein. Aberrant
      aggregation of alpha-synuclein has been detected in an increasing number of
      neurodegenerative diseases, collectively known as synucleopathies. Alpha
      synuclein exists physiologically in both soluble and membrane-bound states, in
      unstructured and alpha-helical conformations, respectively. The physiological
      function of alpha-synuclein appears to require its translocation between these
      subcellular compartments and interconversion between the 2 conformations.
      Abnormal processing of alpha-synuclein is predicted to lead to pathological
      changes in its binding properties and function. In this review, genetic and
      environmental risk factors for alpha-synuclein pathology are described. Various
      mechanisms for in vitro and in vivo alpha-synuclein aggregation and neurotoxicity
      are summarized, and their relevance to neuropathology is explored.

PMID- 15737409
TI  - Sterol transporters: targets of natural sterols and new lipid lowering drugs.
AB  - Recent insights in the role of ATP-binding cassette (ABC) transporters ABCG5 and
      ABCG8, the discovery of ezetimibe, the first approved direct cholesterol
      absorption inhibitor, as well as the identification of Niemann-Pick C1 Like 1
      (NPC1L1) protein as sterol transporter in the gut, focused attention on sterol
      transport processes in the small intestine and the liver. The identification of
      defective structures in the ABCG5 or ABCG8 transporters in patients with the rare
      disease of sitosterolemia elucidated their role as sterol efflux pumps regulating
      at least in parts the intestinal sterol absorption and the hepatic sterol output.
      ABCG5 and ABCG8 themselves are regulated by cholesterol via liver X receptors
      (LXRs), which are also activated by oxysterols and some derivatives of plant
      sterols. NPC1L1 could recently be identified as a major sterol transporter for
      the intestinal uptake of cholesterol as well as plant sterols. Studies in NPC1L1
      knockout mice indicate that this transporter is essential for the intestinal
      uptake of sterols and that NPC1L1 might also be involved in the mechanism of
      action of ezetimibe. However, studies with photoreactive cholesterol as well as
      with photoreactive ezetimibe analogues suggest that other processes might also be
      involved in the mechanism of action of ezetimibe.

PMID- 15737410
TI  - Humoral response and genetic stability of recombinant BCG expressing hepatitis B
      surface antigens.
AB  - The Bacille Calmette Guerin (BCG), long valued for its role as a live vaccine for
      the prevention of tuberculosis, is being used as a recombinant delivery vehicle
      for foreign antigens, principally, for inducing long-lived specific humoral and
      cellular immunity. Hepatitis B and its sequelae are major public health problems.
      Although vaccines have been available for over 20 years the disease remains a
      significant global problem. Many factors contribute to vaccine failure to control
      hepatitis B, including attaining of adequate immune protection. In this study, a
      novel rBCG delivery system is described using non-integrative plasmids harboring
      hepatitis B surface antigen genes. This rBCG was able to elicit an anti-HBs
      response in BALB/c mice. The titres of anti-HBs response obtained using rBCG was
      relatively lower than that of the commercial vaccine used as positive control. In
      vivo or in vitro stability assays showed that the vector used to generate rBCG is
      stable in spite of being a non-integrative plasmid. In addition, the HBsAg
      proteins expression profiles were almost similar to those obtained using an
      Escherichia coli expression system.

PMID- 15737411
TI  - One-step nested PCR for detection of 2 LTR circles in PBMCs of HIV-1 infected
      patients with no detectable plasma HIV RNA.
AB  - A highly sensitive nested PCR was carried out in order to detect 2 LTR circles as
      a marker of recent and ongoing viral replication in HIV-1 infected patients with
      HIV plasma RNA undetectable. This "in house" two-step nested PCR is very
      sensitive, but it is not feasible for routine tests and presents a high risk of
      contamination. In order to reduce the time of reactions and crossover
      contamination, the possibility was explored to carry out a single step nested
      PCR, in which the two successive amplification rounds are carried out in the same
      tube. This single step nested PCR has the same sensitivity of the two-step
      nested, is easy to conduct and requires a short time of reaction. The two
      different PCR methods were compared and the clinical use of monitoring 2 LTR DNA
      circles in HIV-1 infected patients with undetectable plasma viral load is
      discussed.

PMID- 15737412
TI  - The use of fluorescence microscopy to visualise homotypic interactions of tomato
      spotted wilt virus nucleocapsid protein in living cells.
AB  - Fluorescence resonance energy transfer (FRET) and fluorescence lifetime imaging
      microscopy (FLIM) were employed to study homotypic protein-protein interactions
      in living cells. To this end, the nucleocapsid (N) protein of tomato spotted wilt
      virus (TSWV) was expressed as a fusion protein with either cyan fluorescent
      protein (CFP) or yellow fluorescent protein (YFP). Co-expression experiments of
      the two fusion proteins were carried out in baby hamster kidney (BHK21) cells.
      Both the wild type and the fusion proteins showed a peri-nuclear localisation
      pattern and were observed to form aggregates. In sensitised emission experiments,
      energy transfer was observed to take place from CFP to YFP when the two
      fluorophores were fused to TSWV N protein, indicating strongly homotypic
      interaction of the N proteins. This was confirmed by acceptor photobleaching
      studies as well as by FLIM experiments. All three methods showed interactions
      taking place, not only in the aggregates in the peri-nuclear region, but also
      throughout the cytoplasm. These experiments clearly demonstrated the potential of
      these fluorescence methods for studying the interactions of viral proteins in
      living cells.

PMID- 15737413
TI  - Valproic acid enhances gene expression from viral gene transfer vectors.
AB  - Viral vectors represent an efficient delivery method for in vitro and in vivo
      gene transfer, and their utility may be further enhanced through the use of
      pharmacologic agents that increase gene expression. Here, we demonstrate that
      valproic acid (VPA), a drug which is widely used for the treatment of epilepsy
      and mood disorders, enhances and prolongs expression of exogenous genes in cells
      transduced with various gene transfer agents, including adenovirus, adeno
      associated virus and herpesvirus vectors. This effect occurs in a wide range of
      cell types, including both primary cells and cell lines, and appears to be
      associated with VPA's ability to function as a histone deacetylase inhibitor
      (HDACi). VPA treatment also enhanced adenovirally-vectored expression of a
      luciferase reporter gene in mice, as demonstrated by in vivo imaging. VPA was
      also less cytotoxic than a commonly used HDAC inhibitor, TSA, suggesting its use
      as a safer alternative. Taken together, these results suggest that VPA treatment
      may represent a useful approach to various gene transfer approaches in which
      enhanced transgene expression is desirable.

PMID- 15737414
TI  - A novel rapid fluorescent focus inhibition test for rabies virus using a
      recombinant rabies virus visualizing a green fluorescent protein.
AB  - Virus-neutralizing antibodies (VNAs) against rabies virus play a major role in
      protection from rabies. The rapid fluorescent focus inhibition test (RFFIT) has
      been internationally recognized as a standard in vitro test for measuring the
      VNA. CVS strain of rabies virus is used as challenge virus and the infected cells
      are indirectly detected by staining with fluorescein isothiocyanate (FITC)
      conjugated rabies antibody which is expensive and high-quality products are often
      in short supply. In this study, a recombinant rabies virus strain carrying a
      green fluorescent protein (GFP) gene, rHEP-GFP, was used as a challenge virus in
      the virus neutralization assay. Expression of the GFP could be readily detected
      in the infected cells under a fluorescent microscope. This novel RFFIT
      modification RFFIT-GFP is a neutralization test, and it is based on the sound
      principle of the standard RFFIT using 96-well plates. VNA titers in 25 human, 18
      canine and 15 horse sera have been compared between the RFFIT and RFFIT-GFP
      methods. The results obtained by the both methods showed good agreement between
      both methods in all sera investigated (coefficient of correlation, r = 0.98). It
      allowed direct detection of virus by expression of GFP and might be applicable
      for other viruses. The novel method is convenient, economical and a reliable tool
      not requiring expensive FITC-conjugated antibody for routine rabies VNA assays.

PMID- 15737406
TI  - Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the
      induction and maintainance of epilepsy.
AB  - Epilepsy is one of the most common neurological disorders. Although epilepsy can
      be idiopathic, it is estimated that up to 50% of all epilepsy cases are initiated
      by neurological insults and are called acquired epilepsy (AE). AE develops in 3
      phases: (1) the injury (central nervous system [CNS] insult), (2) epileptogenesis
      (latency), and (3) the chronic epileptic (spontaneous recurrent seizure) phases.
      Status epilepticus (SE), stroke, and traumatic brain injury (TBI) are 3 major
      examples of common brain injuries that can lead to the development of AE. It is
      especially important to understand the molecular mechanisms that cause AE because
      it may lead to innovative strategies to prevent or cure this common condition.
      Recent studies have offered new insights into the cause of AE and indicate that
      injury-induced alterations in intracellular calcium concentration levels
      [Ca(2+)](i) and calcium homeostatic mechanisms play a role in the development and
      maintenance of AE. The injuries that cause AE are different, but they share a
      common molecular mechanism for producing brain damage-an increase in
      extracellular glutamate concentration that causes increased intracellular
      neuronal calcium, leading to neuronal injury and/or death. Neurons that survive
      the injury induced by glutamate and are exposed to increased [Ca(2+)](i) are the
      cellular substrates to develop epilepsy because dead cells do not seize. The
      neurons that survive injury sustain permanent long-term plasticity changes in
      [Ca(2+)](i) and calcium homeostatic mechanisms that are permanent and are a
      prominent feature of the epileptic phenotype. In the last several years, evidence
      has accumulated indicating that the prolonged alteration in neuronal calcium
      dynamics plays an important role in the induction and maintenance of the
      prolonged neuroplasticity changes underlying the epileptic phenotype.
      Understanding the role of calcium as a second messenger in the induction and
      maintenance of epilepsy may provide novel insights into therapeutic advances that
      will prevent and even cure AE.

PMID- 15737415
TI  - Development of rhinovirus study model using organ culture of turbinate mucosa.
AB  - To better understand the pathophysiology of rhinovirus (RV) infection, a
      development of a study model using organ culture of turbinate mucosa was sought.
      Inferior turbinate mucosal tissues were cultured using air-liquid interface
      methods, on a support of gelfoam soaked in culture media. RV-16 was applied to
      the mucosal surface and washed off, and histological changes were evaluated. The
      success of RV infection was assayed by semi-nested RT-PCR of the mucosal surface
      fluid taken 48h after incubation. Intracellular RVs were visualized by in situ
      hybridization (ISH). Secretion of the cytokines, IL-6 and IL-8, into the culture
      media was quantitated by ELISA. After 7 days of culture, the turbinate mucosae
      did not show significant damage. A PCR product indicating successful RV infection
      was detected in 5 out of 10 mucosal tissues. ISH showed a very small number of
      positively stained cells focally located in the epithelial layer. In the
      beginning 24h after infection, secretion of IL-6 and IL-8 into the culture media
      of infected mucosae was significantly greater than into the media of control
      mucosae. Our results indicate that the air-liquid interface organ culture of
      turbinate mucosa could serve as an acceptable in vitro model for studying RV
      infection.

PMID- 15737416
TI  - Development of a flow cytometry based method for rapid and sensitive detection of
      a novel marine fish iridovirus in cell culture.
AB  - A sensitive and accurate flow cytometry (FCM) based method has been developed to
      detect and quantitate a novel marine fish iridovirus (Singapore grouper
      iridovirus, SGIV) after amplification in cell cultures. Confluent grouper cell
      (GP) monolayers were infected with SGIV. When advanced cytopathic effect (CPE)
      appeared, the cell cultures were fixed and permeabilized, and then reacted with
      monoclonal antibodies specific against SGIV, followed by a second antibody
      conjugated with FITC (anti-mouse IgG-FITC). A Coulter EPICS Elite ESP flow
      cytometer was used to directly detect and analyze the percentage of virus
      infected cells. Three fixation and permeabilization methods were evaluated. The
      kinetics of the virus infection process was determined. The FCM procedure enables
      large amounts of cells to be screened rapidly for infectivity, and it can also
      detect low levels of virus infection. As early as 8 h after inoculation with the
      virus, 0.34% of infected cells were detected in cell culture. The maximum level
      of infection was obtained at 72 h. The efficiency and reliability of the FCM
      procedure were compared with those of the standard methods of immunofluorescence
      microscopy and PCR.

PMID- 15737417
TI  - Preparation of recombinant African horse sickness virus VP7 antigen via a simple
      method and validation of a VP7-based indirect ELISA for the detection of group
      specific IgG antibodies in horse sera.
AB  - This paper describes the production and purification of a group-specific
      recombinant protein VP7 of African horse sickness virus serotype 3 (AHSV-3) and
      validation of an I-ELISA for the detection of IgG-antibodies to VP7 in horse
      sera. Baculovirus-expressed VP7 crystals were purified from infected insect
      cells. Analytical accuracy of the I-ELISA was examined using sera (n = 38) from
      an experimentally infected horse, from foals born to vaccinated mares, from
      guinea-pigs immunized with nine serotypes of AHSV, and from sera of animals
      infected with other orbiviruses. Compared to traditional serological assays, the
      I-ELISA was more sensitive in detection of the earliest immunological response in
      an infected horse and declining levels of maternal immunity in foals. Antibodies
      to all nine serotypes of AHSV could be detected. Cross-reactivity to related
      orbiviruses was not observed. Diagnostic accuracy of the I-ELISA was assessed by
      testing sera from vaccinated horses (n = 358) residing in AHS-enzootic areas and
      from unvaccinated horses (n = 481) residing in an AHS-free area. Sera were
      categorised as positive or negative for antibodies to AHSV using virus
      neutralisation tests. The TG-ROC analysis was used for the selection of the cut
      off value. At a cut-off of 11.9 of the high positive control serum (percentage
      positivity), the I-ELISA specificity was 100%, sensitivity 99.4%, and the Jouden
      index was 0.99.

PMID- 15737418
TI  - A simplified method for obtaining plant viral RNA for RT-PCR.
AB  - An easy and fast procedure (named the simple-direct-tube (SDT) method) was
      developed for preparing plant virus RNA for cDNA synthesis. The SDT method can be
      completed in approximately 15min and does not require the use of antiserum,
      filtering or centrifugation. The procedure to grind plant tissues in phosphate
      buffered saline containing Tween-20 (PBST) and to place the extract in a
      microfuge tube for a few minutes allow adsorption of the virus particles to the
      tube wall. The sap is then removed and the tube is washed with PBST before the
      addition of RNase-free water. This manipulation can be performed at room
      temperature. Using this method followed by reverse transcription-polymerase chain
      reaction (RT-PCR), infections by turnip mosaic virus, cucumber mosaic virus, and
      cucumber green mottle mosaic virus (CGMMV) were readily detected, indicating that
      the SDT method can be used in assays to detect different viruses. For the
      detection of CGMMV, it was necessary to heat the tubes before cDNA synthesis,
      suggesting that the immobilized CGMMV particles required disruption by heat
      treatment to release RNA.

PMID- 15737419
TI  - PCR detection of dengue virus using dried whole blood spotted on filter paper.
AB  - Whole blood dried onto filter paper constitutes a potentially useful material for
      molecular testing of viruses, including dengue. In order to assess the stability
      of viral RNA, we carried out dengue-RNA detection in whole blood infected with
      dengue virus that had been previously spotted onto filter paper. Filter papers
      were stored at room temperature, 4 and -70 degrees C and processed for PCR assay
      at intervals of 2, 4, 6 and 9 weeks. Our results demonstrated that dengue-RNA was
      stable in filter paper for 9 weeks at all tested temperatures. Furthermore, we
      evaluated these conditions using frozen sera and dried blood samples onto filter
      paper from 52 patients with confirmed clinical diagnosis of dengue infection. PCR
      results showed a 100% specificity and 93% sensitivity for dried blood samples.
      This storage method facilitates the transportation and analysis by nucleic acid
      amplification techniques even when freezing conditions are not available.

PMID- 15737420
TI  - A single nucleotide polymorphism-based technique for specific characterization of
      YO and YN isolates of Potato virus Y (PVY).
AB  - One of the most important properties used to classify Potato virus Y (PVY)
      isolates is their ability to induce (PVY(N)) or not (PVY(O)) veinal necrosis
      symptoms on the indicator host plant Nicotiana tabacum cv. Xanthi. As an
      alternative to biological assays, several serological and molecular detection
      tools have been developed for PVY detection and characterization and these have
      evolved as our knowledge of PVY has improved. However, the assays that have been
      previously published are all based on the use of neutral markers (antigenic
      determinants, sequence data, recombination sites or restriction enzyme cleavage
      sites), which are unlinked to the biological property being characterized (e.g.
      veinal necrosis). Using the recently identified molecular determinants of the
      tobacco leaf necrosis symptom induced by PVY(N) isolates, a one-step fluorescent
      [TaqMan] RT-PCR assay, based on a single nucleotide polymorphism (SNP) linked to
      the necrosis property of PVY isolates, has been designed. This assay reliably
      detects and distinguishes PVY(N) and PVY(O) isolates. The method is simple (leaf
      soak extraction process, gel-free, no post-PCR manipulations), rapid (96 tests in
      less than 3h from plants sampling to diagnostic results), sensitive (threshold in
      a range of 10(4)-10(5) PVY copies), reliable (correctly assigns 42 PVY isolates
      in their respective group) and allows co-detection of mixed samples containing
      close to equivalent PVY(N) and PVY(O) quantities. All these characteristics
      suggest that the newly developed SNP assay could be used to reliably classify PVY
      isolates, as a substitute for biological assays performed on N. tabacum cv.
      Xanthi.

PMID- 15737421
TI  - Persistence of DNA in cell cultures may jeopardize the analysis of human
      herpesvirus 6 dynamics by means of real-time PCR.
AB  - The use of real-time PCR has been described previously for analysing both the
      replication kinetics and antiviral susceptibility of human herpesvirus 6 in MT4
      cells. It is now reported that viral DNA persists in infected cell culture long
      after the end of lytic virus replication. Consequently, high levels of DNA may
      correspond to an absence of infectivity and late readout occurring after the
      exponential phase of virus growth may lead to misinterpretation of the results of
      susceptibility assays. These limitations must be borne in mind when using real
      time PCR.

PMID- 15737422
TI  - Proceedings of the plenary sessions of the Tenth Symposium of the International
      Society for Veterinary Epidemiology and Economics (ISVEE). November 2003. Vinal
      del Mar, Chile.

PMID- 15737423
TI  - The state of veterinary epidemiology and economics.
AB  - Recent developments in the fields of veterinary epidemiology and economics are
      critically reviewed and assessed. The impacts of recent technological
      developments in diagnosis, genetic characterisation, data processing and
      statistical analysis are evaluated. It is concluded that the acquisition and
      availability of data remains the principal constraint to the application of
      available techniques in veterinary epidemiology and economics, especially at
      population level. As more commercial producers use computerised management
      systems, the availability of data for analysis within herds is improving.
      However, consistency of recording and diagnosis remains problematic. Recent
      trends to the development of national livestock databases intended to provide
      reassurance to consumers of the safety and traceability of livestock products are
      potentially valuable sources of data that could lead to much more effective
      application of veterinary epidemiology and economics. These opportunities will be
      greatly enhanced if data from different sources, such as movement recording,
      official animal health programmes, quality assurance schemes, production
      recording and breed societies can be integrated. However, in order to realise
      such integrated databases, it will be necessary to provide absolute control of
      user access to guarantee data security and confidentiality. The potential
      applications of integrated livestock databases in analysis, modelling, decision
      support, and providing management information for veterinary services and
      livestock producers are discussed.

PMID- 15737424
TI  - Globalization, international trade and animal health: the new roles of OIE.
AB  - In order for countries and their stakeholders to maximize the benefits of
      globalization they must become familiar with, and must adhere to, the rights and
      obligations set out by the World Trade Organization (WTO) under the Agreement on
      Sanitary and Phytosanitary Measures (SPS). For the purpose of trade in animals
      and animal products, they must also adhere to the standards, guidelines and
      recommendations established by the World Organisation for Animal Health (OIE).
      Countries are also encouraged to participate in this standard setting process of
      the OIE. Only after implementing these requirements and after strengthening the
      veterinary infrastructures and their surveillance and monitoring systems, will
      countries be able to fully benefit from these new international trade rules.

PMID- 15737425
TI  - Portrait of the national veterinary service as a surveillance continuum.
AB  - National veterinary services emerged in response to the animal disease challenges
      of centuries past. Their often singular preoccupation with exogenous disease
      preclusion yielded, by the early 1900s, to parallel commitments to control a
      number of serious indigenous, zoonotic infections. Advances in clinical pathology
      and epidemiology opened the door in many countries to disease, if not agent,
      eradication initiatives by the latter part of that century. The attending
      interval witnessed the explosive growth of international trade and the emerging
      or re-emerging conditions that threaten to accompany it. Animal disease agents,
      their hosts and the environments within which they interact vary considerably
      from nation to nation. Depicted as a medieval metaphor, the exogenous cluster
      around the walls of the castle, awaiting entry upon the next uninspected,
      unsuspecting fomite or beast. Some of these threats reside comfortably within the
      structure's bedding and detritus, sapping the vitality of its residents until
      detected and exterminated. Others emerge from the least expected crevices,
      growing insidiously or explosively in tandem with changes wrought by humans or
      nature. In anticipation of, or in response to, these myriad challenges, national
      veterinary services mount surveillance campaigns. From the national survey that
      denies the presence of exogenous disease to the post-eradication assessment that
      confirms its demise, surveillance forms the sensory acumen of the service. From
      the passive assessments that detect the emerging to the active regimens that plot
      progress against the indigenous, they form a continuum that defines the very
      nature of the national veterinary service.

PMID- 15737426
TI  - Epidemiological approach to aquatic animal health management: opportunities and
      challenges for developing countries to increase aquatic production through
      aquaculture.
AB  - Aquaculture appears to have strongest potential to meet the increasing demands
      for aquatic products in most regions of the world. The world population is on the
      increase, as is the demand for aquatic food products. Production from capture
      fisheries at a global level is levelling off. Potential contributions from
      aquaculture to local food security, livelihoods and nutrition can be highly
      significant, especially in many remote and resource-poor rural areas. One of the
      major constraints to aquaculture production is the losses due to diseases. Over
      the decades, the sector has faced significant problems with disease outbreaks and
      epidemics which caused significant economic losses. The use of sound
      epidemiological principles and logical and science-based approach to identify and
      manage risks comprise two of the most important components of an effective
      biosecurity program. The maintenance of effective biosecurity in aquaculture is
      becoming more and more essential. There will be more demand for aquatic animal
      epidemiologists as well as epidemiological tools/resources in the region. The use
      of epidemiology will significantly improve health management, risk analysis and
      disease control. Although there are clear limitations and complications in the
      use of epidemiology for controlling aquatic animal pathogens, some positive
      results have recently emerged from a series of studies and trials to control
      diseases affecting the small-scale shrimp farming sector in southern India. This
      paper summarises the results of one such study which emphasizes the significant
      benefit of close collaboration with farmers, both individually and as groups, and
      capacity and awareness building among them and the importance of understanding
      the risk factors and implementing better management practices.

PMID- 15737427
TI  - The role of veterinary epidemiology and veterinary services in complying with the
      World Trade Organization SPS agreement.
AB  - The agreement on the application of sanitary and phytosanitary measures (SPS
      agreement) was one of the major products of the GATT's Uruguay round of
      multilateral trade negotiations, signed in Marrakesh on 15 April 1994. This
      agreement and others are part of the treaty that established the World Trade
      Organization (WTO). The WTO superseded the GATT as the umbrella organization for
      international trade (WTO, 1998a). The SPS agreement's main intent is to provide
      guidelines and provisions to member countries to facilitate trade while taking
      measures to protect human, animal or plant life or health. The agreement dictates
      that all sanitary measures must be scientifically based and not more restrictive
      than required to avoid the risk identified. The agreement recommends the use of
      international standards from the World Organization for Animal Health (OIE),
      Codex Alimentarius (CAC) and the International Plant Protection Convention (IPPC)
      as the basis for import requirements. If a country chooses to apply more
      restrictive measures than those in the international standards, it has to justify
      its position through a risk analysis, thus avoiding the use of sanitary and
      phytosanitary measures as unjustified barriers to trade. More than ever,
      veterinary services worldwide are faced with having to fulfill a crucial role in
      protecting their country's animal health status, provide sound surveillance
      information on the occurrence of diseases within their territories, and conduct
      scientifically valid risk analyses to establish justified import requirements.
      During the past two decades, most countries have experienced resource reduction
      in their veterinary services. The effect of these policies has been severe, in
      many cases leading to an inability of veterinary services to conduct their
      disease prevention and control duties. There is a clear inconsistency between the
      demands placed on veterinary services and the current level of funding and
      support they are receiving, particularly in the developing world. This paper
      analyzes the implications in complying with the SPS agreement and explores the
      role of veterinary epidemiology in developing viable alternatives that can
      enhance the veterinary services' ability to perform under the current economic
      reality. The key provisions of the SPS agreement are regionalization, risk
      analysis, harmonization, equivalence and transparency. The paper focuses on the
      contribution of epidemiology in each of these areas in the effective
      implementation of the SPS agreement.

PMID- 15737428
TI  - A modelling framework to describe the spread of scrapie between sheep flocks in
      Great Britain.
AB  - My aim was to develop a stochastic, spatial model describing the spread of
      scrapie between sheep flocks in Great Britain; I wanted a model, which could
      subsequently be used to assess the efficacy of different control strategies. The
      structure of the model reflects the demography of the British sheep flock,
      including a description of the contact structure between flocks. The dynamics of
      scrapie were incorporated through two probabilities associated with each flock:
      of acquiring infection and of experiencing a within-flock outbreak following
      exposure. The acquisition of infection depends on whether or not a flock buys-in
      sheep and, if it does, whether or not it trades with an affected flock. Once a
      flock is exposed, the probability of a within-flock outbreak occurring and its
      duration depend on the basic reproductive number, the prion-protein (PrP)
      genotype profile and the flock size. The model was validated using regional data
      from two postal surveys conducted in 1998 and 2002, which demonstrated that the
      model captures the spatial dynamics of scrapie (at least at a regional level).
      Moreover, the predicted distribution for the duration of a within-flock outbreak
      reflects the duration of outbreaks reported in the literature. Using the model to
      predict long-term trends in the proportion of affected flocks suggested that,
      even without control measures beyond the removal of animals with clinical signs,
      scrapie ultimately will disappear from the national flock, though it is likely to
      be decades before the disease is eliminated. However, there were scenarios
      consistent with the available data which suggested that scrapie could remain
      endemic within the British sheep flock. Consequently, it is essential to take
      this uncertainty in the long-term dynamics of scrapie into account when
      considering the efficacy of control strategies. Although control strategies were
      not explicitly examined, the model suggests two aspects important for control:
      larger flocks remain affected for longer and provide infection for other, smaller
      flocks and animal movements must be traceable.

PMID- 15737430
TI  - Attitudes of New Zealand farmers to methods used to control wild rabbits.
AB  - Four years after the release of Rabbit haemorrhagic disease virus (RHDV) in New
      Zealand, we conducted a mail survey of farmers to ascertain their attitudes and
      practices about rabbit control. A multistage sampling frame (stratified by rabbit
      proneness and farm type) was used to select 828 farms in eight geographical
      regions. The useable response proportion of the survey was 69.3%, and 21% of
      respondents considered rabbits to be a problem on their farms. Although practices
      for rabbit control had changed from 1995 to 2001, shooting (practised by 85% of
      respondents) remained the predominant method used (albeit less frequently than in
      1995). Ten percent of farmers used RHDV baiting; of those, 90% released the virus
      relatively infrequently. Farmers perceived shooting to be the most-humane and
      environmentally safe method, while RHDV was perceived to be the most effective.
      Perception of the level of competition for grazing between rabbits and livestock
      was the factor most-strongly associated with the use of shooting and RHDV. Most
      (60%) respondents considered the introduction of RHDV to have been beneficial.

PMID- 15737429
TI  - Risk factors for tick attachment to smallholder dairy cattle in Tanzania.
AB  - A cross-sectional study was conducted in Tanga and Iringa regions of Tanzania,
      and a longitudinal study in Tanga, to investigate tick-control methods and other
      factors influencing tick attachment to the cattle of smallholder dairy farms.
      Most farmers reported applying acaricides at intervals of 1-2 weeks, most used
      acaricides that require on-farm dilution and most farmers incorrectly diluted the
      acaricides. Rhipicephalus appendiculatus and Boophilus spp. ticks were those most
      frequently encountered on the cattle, but few cattle carried ticks of any species
      (only 13 and 4.6% of tick counts of the cattle yielded adult R. appendiculatus
      and Boophilus spp., respectively). Animals were more likely to carry one or more
      adult Boophilus spp. ticks if they also carried one or more R. appendiculatus
      adults (OR=14.4, CI=9.2, 22.5). The use of pour-on acaricides was associated with
      lower odds that animals carried a R. appendiculatus tick (OR=0.29, CI=0.18, 0.49)
      but higher odds that they carried a Boophilus spp. tick (OR=2.48, CI=1.55, 3.97).
      Animals >4 months old and those with a recent history of grazing had higher odds
      of carrying either a R. appendiculatus (ORs=3.41 and 2.58, CIs=2.34, 4.98 and
      1.80, 3.71), or a Boophilus spp. tick (ORs=5.70 and 2.18, CIs=2.34, 4.98 and
      1.49. 3.25), but zero-grazing management did not prevent ticks attaching to
      cattle even when combined with high-frequency acaricide treatments. The odds that
      animals carried ticks varied amongst the agro-ecological zones (AEZs) and
      administrative districts where the farms were situated-but there was still
      considerable residual variation in tick infestation at the farm level.

PMID- 15737431
TI  - When can a veterinarian be expected to detect classical swine fever virus among
      breeding sows in a herd during an outbreak?
AB  - The herd sensitivity (HSe) and herd specificity (Hsp) of clinical diagnosis of an
      infection with classical swine fever (CSF) virus during veterinary inspection of
      breeding sows in a herd was evaluated. Data gathered from visits to herds during
      the CSF outbreak in 1997-1998 in The Netherlands were used for the analysis.
      Herds were visited one or more times by the same or by different veterinarians.
      On the basis of the veterinarians' reports, each visit was coded as 0 (negative
      clinical diagnosis) or 1 (positive clinical diagnosis). The HSe for clinical
      diagnosis of CSF was modelled as a function of days elapsed since introduction of
      the virus. The moment of introduction of the CSF virus in the CSF-positive herds
      was unknown, so for each herd, a probability distribution for the unknown number
      of days since introduction was derived from serum samples collected at
      depopulation. The information from the reports of the veterinarians and from the
      test results of the serum samples at depopulation was combined in a Bayesian
      analysis. Data from CSF-negative herds were analysed to estimate HSp of clinical
      diagnosis of CSF. The HSe of clinical diagnosis was 0.5 at 37 days after virus
      introduction (95% CI: 31, 45) and reached 0.9 at 47 days after virus introduction
      (95% CI: 41, 54). The estimated herd specificity was 0.72 (95% CI: 0.64, 0.79).
      Dependence of HSe and HSp on characteristics of the veterinarians and the herds
      also was studied. Specialisation of the veterinarian significantly, although not
      markedly, affected the HSe.

PMID- 15737432
TI  - Effect of medium- and long-chain triglyceride supplementation on small newborn
      pig survival.
AB  - The pre-weaning survival of 508 piglets was studied with a categorical survival
      analysis, evaluating the effect of medium-long-chain triglyceride (MCT-LCT)
      supplementation on small newborn pigs, and determining additional risk factors.
      Half of the 98 piglets born with birth weight (BW)<1250 g received 1.95 g of MCT
      LCT each 24 h during the first 3 days of life, and their death hazard was reduced
      1.9-fold in relation with small unsupplemented siblings. The death hazard ratio
      (HR) of supplemented animals compared to 410 heavier littermates was not
      different. However, the HR for newborn pigs that were small in relation with
      their siblings was 2.8, and the HR for litters with >12 piglets born alive was
      4.5. There was variation across months, and also piglets from primiparous sows
      had increased hazard of death (HR=4.0).

PMID- 15737433
TI  - A framework for understanding the potential for emerging diseases in aquaculture.
AB  - Numerous diseases have emerged as serious economic or ecological problems in
      aquaculture species. The combination of factors behind the emergence of each
      disease is unique, but various common factors are apparent. We combine risk
      analysis methods and virulence theory with historical examples (mainly from
      salmonid production) to identify key disease-emergence risk factors. Diseases
      have emerged through pathogen exchange with wild populations, evolution from non
      pathogenic micro-organisms and anthropogenic transfer of stocks. Aquacultural
      practices frequently result in high population densities and other stresses (such
      as intercurrent disease) which increase the risk of infection establishment and
      spread. As aquaculture expands and new species are farmed, diseases will continue
      to emerge and affect both wild and farmed fish adversely. The rate and extent of
      emergence can be reduced by the application of biosecurity programmes designed to
      mitigate the risk factors for disease emergence.

PMID- 15737434
TI  - Disease-related regressive alterations of forebrain cholinergic system in SOD1
      mutant transgenic mice.
AB  - Transgenic mice carrying the human mutated SOD1 gene with a glycine/alanine
      substitution at codon 93 (G93A) are a widely used model for the fatal human
      disease amyotrophic lateral sclerosis (ALS). In these transgenic mice, we carried
      out a neurochemical study not only restricted to the primarily affected regions,
      the cervical and lumbar segments of the spinal cord, but also to several other
      brain regions. At symptomatic (110 and 125 days of age), but not at pre
      symptomatic (55 days of age) stages, we found significant decreases in catalytic
      activity of the cholinergic enzyme, choline acetyltransferase (ChAT) in the
      hippocampus, olfactory cortex and fronto-parietal cortex. In parallel, we
      observed a decreased number of basal forebrain cholinergic neurons projecting to
      these areas. No alterations of the cholinergic markers were noticed in the
      striatum and the cerebellum. A widespread marker for GABAergic neurons, glutamate
      decarboxylase (GAD), was unaffected in all the areas examined. Alteration of
      cholinergic markers in forebrain areas was paralleled by concomitant alterations
      in the spinal cord and brainstem, as a consequence of progressive apoptotic
      elimination of cholinergic motor neuron. Gestational supplementation of choline,
      while able to result in long-term enhancement of cholinergic activity, did not
      improve transgenic mice lifespan nor counteracted cholinergic impairment in brain
      regions and spinal cord.

PMID- 15737436
TI  - Characterization of cells with proliferative activity after a brain injury.
AB  - The cellular responses to a brain injury are important steps in restoring the
      integrity and function of the brain. Proliferating cells, such as reactive
      astrocytes, oligodendrocyte precursor cells and microglia remodel the injured
      tissue. To spatially and temporally characterize the initial cellular responses
      in vivo, proliferating cells were pulse-labeled with BrdU soon after (the 2nd
      day) a cortical cryo-injury, and their fate was investigated by double labeling
      with an anti-BrdU antibody and antibodies to various cellular markers. Three days
      after the cryo-injury, a significant proportion of BrdU-positive cells were
      positive for NG2-proteoglycan, suggesting that oligodendrocyte progenitors (OPCs)
      were induced in response to injury. One-two weeks after the cryo-injury, the
      number of OPC was reduced and GFAP/BrdU double-positive cells, in turn, became
      dominant, while cells with mature oligodendrocyte markers did not increase
      significantly. Neuronal markers were rarely co-localized with BrdU
      immunoreactivity throughout the period studied. These findings imply that OPCs
      are prone to differentiate to astrocytes in the lesioned site. In this cryo
      injury model, treatment with thyroid hormone (T4) altered cell fate; the increase
      in the number of GFAP/BrdU-positive cells was significantly diminished, and there
      was an increased number of mature oligodendrocytes (CNPase, PLP-positive)
      exhibiting BrdU immunoreactivity. These findings suggest that modification of
      proliferating progenitors in injured brain by hormonal or chemical treatment
      might benefit functional regeneration.

PMID- 15737437
TI  - Cysteamine prevents and reverses the inhibition of creatine kinase activity
      caused by cystine in rat brain cortex.
AB  - Cystinosis is a disorder associated with lysosomal cystine accumulation caused by
      defective cystine efflux. Cystine accumulation provokes a variable degree of
      symptoms depending on the involved tissues. Adult patients may present brain
      cortical atrophy. However, the mechanisms by which cystine is toxic to the
      tissues are not fully understood. Considering that brain damage may be developed
      by energy deficiency, creatine kinase is a thiolic enzyme crucial for energy
      homeostasis, and disulfides like cystine may alter thiolic enzymes by
      thiol/disulfide exchange, the main objective of the present study was to
      investigate the effect of cystine on creatine kinase activity in total
      homogenate, cytosolic and mitochondrial fractions of the brain cortex from 21-day
      old Wistar rats. We performed kinetic studies and investigated the effects of
      GSH, a biologically occurring thiol group protector, and cysteamine, the drug
      used for cystinosis treatment, to better understand the effect of cystine on
      creatine kinase activity. Results showed that cystine inhibited the enzyme
      activity non-competitively in a dose- and time-dependent way. GSH partially
      prevented and reversed CK inhibition caused by cystine and cysteamine fully
      prevented and reversed this inhibition, suggesting that cystine inhibits creatine
      kinase activity by interaction with the sulfhydryl groups of the enzyme.
      Considering that creatine kinase is a crucial enzyme for brain cortex energy
      homeostasis, these results provide a possible mechanism for cystine toxicity and
      also a new possible beneficial effect for the use of cysteamine in cystinotic
      patients.

PMID- 15737435
TI  - Inducible expression and pharmacological characterization of recombinant rat
      NR1a/NR2A NMDA receptors.
AB  - In this study, we have established a non-neuronal cell line stably and inducibly
      expressing recombinant NMDA receptors (NRs) composed of rat NR1a/NR2A subunits.
      EcR-293 cells were transfected with rat NR1a and NR2A cDNAs using the inducible
      mammalian expression vector pIND. Cell colonies resistant for the selecting
      agents were picked and tested for NR2A mRNA as well as protein expression using
      quantitative RT-PCR and flow cytometry based immunocytochemistry. Clonal cells
      expressing functional NMDA receptors were identified by measuring NMDA-evoked ion
      currents, and NMDA-induced increase in cytosolic free calcium concentration in
      whole-cell patch-clamp and fluorimetric calcium measurements, respectively. One
      clone named D5/H3, which exhibited the highest response to NMDA, was chosen to
      examine inducibility of the expression and for pharmacological profiling of
      recombinant NR1a/NR2A NMDA receptors. To check inducibility, NR2A subunit
      expression in D5/H3 cells treated with the inducing agent muristerone A (MuA) was
      compared with that in non-induced cells. Both NR2A mRNA and protein expression
      was several folds higher in cells treated with the inducing agent. As part of the
      pharmacological characterization, we examined the activation of the expressed
      NR1a/NR2A receptors as a function of increasing concentration of NMDA. NMDA
      evoked concentration-dependent increases in cytosolic [Ca2+] with an EC50 value
      of 41 +/- 1 microM. In addition, whereas the NMDA response was concentration
      dependently inhibited by the channel blocker MK-801 (IC50 = 58 +/- 6 nM), NR2B
      subunit selective NMDA receptor antagonists were ineffective. Thus, this cell
      line, which stably and inducibly expresses recombinant NR1a/NR2A NMDA receptors,
      can be a useful tool for testing NMDA receptor antagonists and studying their
      subunit selectivity.

PMID- 15737438
TI  - Dehydroascorbic acid normalizes several markers of oxidative stress and
      inflammation in acute hyperglycemic focal cerebral ischemia in the rat.
AB  - We investigated the effect of dehydroascorbic acid (DHA), the oxidized form of
      vitamin C which is a superoxide scavenger, on manganese superoxide dismutase
      (MnSOD), copper-zinc SOD (CuZnSOD), cyclooxygenase-2 (COX-2) and interleukin
      1beta (IL-1beta) expression in a rat model of focal cerebral ischemia under normo
      and hyperglycemic conditions. Edema formation was also assessed. MnSOD, CuZnSOD,
      COX-2 and IL-1beta mRNA and protein expression were studied 3 h post-ischemia. No
      changes were observed in MnSOD and CuZnSOD mRNA expression among the groups. COX
      2 and IL-1beta mRNA expression were upregulated by ischemia but were not
      influenced by the glycemic state. At the protein level, hyperglycemic cerebral
      ischemia increased MnSOD and CuZnSOD [Bemeur, C., Ste-Marie, L., Desjardins, P.,
      Butterworth, R.F., Vachon, L., Montgomery, J., Hazell, A.S., 2004a. Expression of
      superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat.
      Neurochem. Int. 45, 1167-1174] and IL-1beta expression compared to normoglycemic
      ischemia. COX-2 protein expression was also significantly higher following
      hyperglycemic ischemia compared to hyperglycemic shams. DHA administration did
      not change the pattern of COX-2 or IL-1beta mRNA expression, but normalized the
      increased protein expression following hyperglycemic ischemia. DHA administration
      also normalized MnSOD and CuZnSOD protein expression to the levels observed in
      normoglycemic ischemic animals. Edema formation was significantly reduced by DHA
      administration in hyperglycemic ischemic animals. The DHA-induced post
      transcriptional normalization of MnSOD, CuZnSOD, COX-2 and IL-1beta levels and
      the decreased edema formation suggest that hyperglycemia accelerates superoxide
      formation and the inflammatory response, thus contributing to early damage in
      hyperglycemic stroke and strategies to scavenge superoxide should be an important
      therapeutic avenue.

PMID- 15737439
TI  - Analysis of cholinergic markers, biogenic amines, and amino acids in the CNS of
      two APP overexpression mouse models.
AB  - Two transgenic mouse models expressing mutated human amyloid precursor protein
      and previously found to display cognitive and behavioural alterations,
      reminiscent of Alzheimer patients' symptomatology, were scrutinised for putative
      brain region-specific changes in neurochemical parameters. Brains of NSE-hAPP751m
      57, APP23 and wild-type mice were microdissected to perform brain region-specific
      neurochemical analyses. Impairment of cholinergic transmission, the prominent
      neurochemical deficit in Alzheimer brain, was examined; acetylcholinesterase and
      choline acetyltransferase activity levels were determined as markers of the
      cholinergic system. Since Alzheimer neurodegeneration is not restricted to the
      cholinergic system, brain levels of biogenic amines and metabolites, and amino
      acidergic neurotransmitters and systemic amino acids were analysed as well.
      Cholinergic dysfunction, reflected in reduced enzymatic activity in the basal
      forebrain nuclei, was restricted to the APP23 model, which also exhibited more
      outspoken and more widespread changes in other neurotransmitter systems.
      Significant changes in compounds of the noradrenergic and serotonergic system
      were observed, as well as alterations in levels of the inhibitory
      neurotransmitter glycine and systemic amino acids. These observations were
      clearly in occurrence with the more pronounced histopathological and behavioural
      phenotype of the APP23 model. As transgenic models often do not represent an end
      stage of the disease, some discrepancies with results from post-mortem human
      Alzheimer brain analyses were apparent; in particular, no significant alterations
      in excitatory amino acid levels were detected. Our findings of brain region
      specific alterations in compound levels indicate disturbed neurotransmission
      pathways, and greatly add to the validity of APP23 mice as a model for
      Alzheimer's disease. Transgenic mouse models may be employed as a tool to study
      early-stage neurochemical changes, which are often not accessible in Alzheimer
      brain.

PMID- 15737440
TI  - Rat choline acetyltransferase of the peripheral type differs from that of the
      common type in intracellular translocation.
AB  - Choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine, has
      been implicated to involve multiple isoforms of ChAT mRNA in several animals.
      Since these isoforms are mostly non-coding splice variants, only a homologous
      ChAT protein of about 68 kDa has been shown to be produced in vivo. Recent
      evidence indicates the existence of a protein coding splice variant of ChAT mRNA,
      which lacks exons 6-9 of the rat ChAT gene. The encoded protein was designated
      ChAT of a peripheral type (pChAT), because of its preferential expression in the
      peripheral nervous system as confirmed by Western blot and immunohistochemistry.
      However, functional significance of pChAT is unknown. To obtain a clue to this
      question, we examined a possible difference in intracellular trafficking between
      pChAT and the well-known ChAT of the common type (cChAT) using green fluorescent
      protein (GFP) in living human embryonic kidney cells. Confocal laser scanning
      microscopy revealed that pChAT-GFP was detectable in the cytoplasm but not in the
      nucleus, whereas cChAT-GFP was found in both cytoplasm and nucleus. Following
      treatment with leptomycin B, a nuclear export pathway inhibitor, pChAT-GFP became
      detectable in both cytoplasm and nucleus, indicating that pChAT can be
      translocated to the nucleus. In contrast, the leptomycin B treatment did not seem
      to affect the content of intranuclear cChAT-GFP. After incubation with protein
      kinase C inhibitors, enhanced accumulation of pChAT-GFP but not cChAT-GFP
      occurred in the nucleus. These results clearly indicate that pChAT varies from
      cChAT in intracellular transportation, probably reflecting the difference in
      physiological roles between pChAT and cChAT.

PMID- 15737441
TI  - Kinematic and electromyographic response to whiplash loading in low-velocity
      whiplash impacts--a review.
AB  - Whiplash injury is a common injury, with a substantial health and economic
      burden. For five decades, researchers have been striving to discover the
      mechanisms of acute whiplash injury to develop methods of prevention through
      automobile design, and to develop treatment approaches. While earlier experiments
      with animals, cadavers, and military volunteers have provided some useful
      insights, it is only in recent years that research has progressed to reveal how
      neck muscles respond to collisions, particularly how they bear the burden of the
      forces of collision and how impact direction affects the neck muscle response
      which may determine the mechanism of injury. Initial volunteer experiments tended
      to focus on impact velocities (specifically differences in target and bullet
      vehicle velocities) and head acceleration, but gradually the focus has shifted to
      understanding the pattern of spinal segment motion and muscle contraction in
      response to the perturbation. An approach has been devised using sled impacts
      with healthy volunteers to elucidate in more detail various head kinematics and
      cervical muscle responses in low-velocity whiplash-type impacts. This approach
      involves the use of four levels of very-low to low velocity impacts to describe
      the kinematics of the head and the EMG response of cervical muscles in response
      to acceleration, but avoids any discernible risk of injury. This allows
      researchers to determine the cervical muscle response under many different
      scenarios, including varying direction of impact, awareness of impending impact,
      and others, without subjecting volunteers to any discernible risk. An initial
      series of results of impacts from eight directions is presented here, and these
      reveal that the cervical response to whiplash-type impacts is modified by impact
      awareness, muscles studied, and direction of impact. This will hopefully improve
      the understanding of the human response to low-velocity whiplash impacts.

PMID- 15737443
TI  - The influence of different unloading positions upon stature recovery and
      paraspinal muscle activity.
AB  - OBJECTIVE: To determine whether stature recovery and paraspinal muscle activity
      can be altered in individuals with and without chronic low-back pain by assuming
      different unloading positions. DESIGN: A case-control study considering the
      effects of unloading position on stature recovery in individuals with and without
      chronic low-back pain. BACKGROUND: Stature recovery has been documented to be
      lower in individuals with chronic low-back pain. Elevated paraspinal muscle
      activity subjects the spine to increased compression, which may delay stature
      recovery. However, the mechanism(s) causing prolonged stature recovery are yet to
      be explored. METHODS: Eleven chronic low-back pain participants (age 33 yr (SD
      12.2), height 1.72 m (SD 0.08), body mass 75.9 kg (SD 10.7)) and eleven
      asymptomatic participants (age 30.5 yr (SD 9.7), height 1.75 m (SD 0.10), body
      mass 73.3 kg (SD 11.7)) performed a loaded walking task (10% body mass) and
      adopted four unloading positions on separate occasions. Measurements of stature
      and muscle activity were recorded during each position. FINDINGS: Individuals
      with chronic low-back pain exhibited higher paraspinal EMG and delayed stature
      recovery in all positions (P<0.05). Both groups experienced greatest stature
      recovery and least muscle activity during gravity inversion (P<0.05).
      INTERPRETATION: Elevated muscle activity was found in the chronic low-back pain
      group supporting the existence of this explanation for delayed stature recovery.
      The gravity inverted position resulted in the lowest EMG and the greatest stature
      recovery. Further research is required to determine whether improving stature
      recovery has clinical implications by reducing pain/disability.

PMID- 15737442
TI  - The impact of total lumbar disc replacement on segmental and total lumbar
      lordosis.
AB  - BACKGROUND: One of the goals of total lumbar disc replacement is restoration of
      the physiological sagittal alignment. There is little evidence if this goal is
      reached in vivo and further affects the clinical outcome. METHODS: In 29 patients
      segmental lordosis and total lumbar lordosis were measured on X-rays pre- and
      postoperatively. The functional outcome was evaluated prospectively with the
      Visuell Analogue Scale, Oswestry Low Back Pain Disability Questionnaire and Short
      Form 36 Health Survey Questionnaire. FINDINGS: Total disc replacement increased
      segmental lordosis significantly while total lumbar lordosis remained unchanged.
      Preoperative segmental/total lumbar lordosis was physiological in 52%/91% of the
      patients. Postoperatively these values changed to 72% for segmental- and 94% for
      total lumbar lordosis. No difference could be observed in clinical outcome
      measures in patients with physiological and unphysiological segmental lordosis.
      INTERPRETATION: Monosegmental total disc replacement increases the segmental
      lordosis in most of the cases while preserving the total lumbar lordosis which
      produces a decrease of lordotic angle in the adjacent segment(s). Although short
      term clinical results are not affected, the segmental lordosis increase and
      adjacent segment(s) alteration may influence long term outcome.

PMID- 15737444
TI  - Absorbed power of small children.
AB  - OBJECTIVE: To experimentally measure the seated vertical direction whole-body
      absorbed power characteristics of small children less than 18 kg in mass.
      BACKGROUND: Several studies have reported whole-body absorbed power for adult
      humans, but no data has been published previously for small children. METHODS:
      Eight children were tested in a laboratory test rig which incorporated safety
      features which satisfy existing international standards for human testing. Force
      and acceleration were measured at the point of input to a rigid seat at a
      sampling rate of 200 Hz, and analysis was performed over the interval from 1.0 to
      45.0 Hz. A double normalised (both input acceleration and test subject mass)
      measure of absorbed power was used. RESULTS: The vertical whole-body power
      absorption characteristics of the small children were found to present
      differences with respect to those of adults. The mean frequency of peak
      absorption was found to be 7.4 Hz as opposed to approximately 4.0-5.0 for adults.
      The interval of absorption was found to be from approximately 3 to 16 Hz and the
      total double normalised absorbed power was found to be 86% that of adults.
      CONCLUSIONS: The differences in dynamic response between small children and
      adults raise questions regarding the applicability of whole-body vibration
      guidelines such as ISO-2631 in the case of small children since these guidelines
      were developed from mechanical and subjective response data of adults. Relevance
      Knowledge of the differences in whole-body vibration response between small
      children and adults is useful towards the design of systems intended for children
      such as child seats. The child data may also prove useful should absorbed power
      find application as a screening tool in clinical settings.

PMID- 15737445
TI  - Kinematical measure for spastic reaching in children with cerebral palsy.
AB  - BACKGROUND: Practitioners need more sensitive measure to quantify reaching
      movement for judgment of the treatment effects and reflecting the degrees of
      motor impairment in upper extremities. The purposes of this study were to
      identify the specific kinematic characteristics between normal and spastic
      reaching under different levels of accuracy, and to determine the most sensitive
      kinematic variable for quantifying the interference of spasticity on reaching.
      METHODS: Ten normal subjects as control group and ten subjects with spastic
      cerebral palsy as experimental group were studied. Participants were asked to
      reach, at a self-selected pace, toward two different sizes of buttons (one with
      accuracy constraint and the other with non-accuracy constraint) away from
      normalized distance. Motion analysis system was used to record the trajectory of
      reaching performance. Kinematic variables of reaching movement were computed and
      analyzed. FINDINGS: Measure for movement smoothness presented larger effect size
      (0.24-0.43) than other kinematic variables adopted in this study. Under high
      accuracy reaching, children with spastic cerebral palsy had a prolonged movement
      time than normal children (P<0.05). Modified Ashworth score was significantly
      correlated to normalized jerk score, number of movement unit and movement time
      (r=0.56-0.75). Number of movement unit was the most sensitive kinematic variable
      to discriminate between normal and spastic reaching. INTERPRETATION: Development
      of reliable, valid, and sensitive multi-joint biomechanical evaluation is
      required, particularly for natural and goal-oriented reaching movement. It is
      concluded that measure of movement smoothness may be applied as valid and
      sensitive index to quantify the level of coordinative motor performance for
      subjects with spastic movement disorder.

PMID- 15737446
TI  - The effect of divided attention on gait stability following concussion.
AB  - BACKGROUND: The need to identify functional impairment following a brain injury
      is critical to prevent re-injury during the period of recovery. While many
      neuropsychological tests have been developed to assess cognitive performance,
      relatively little information on gait and dynamic stability is available on motor
      task performance for young adults following concussion. This study was performed
      to investigate the effect of divided attention following concussion on various
      gait variables. It was hypothesized that, when compared to uninjured controls,
      concussed subjects would demonstrate deficits in maintenance of dynamic
      stability. METHODS: Ten subjects with Grade 2 concussion completed testing within
      48 h of injury as well as 10 age-, height-, weight-, and activity-matched
      controls. The gait protocol consisted of level walking under two conditions: (1)
      undivided attention (single-task) and (2) while simultaneously completing simple
      mental tasks (dual-task). Whole-body motion data were collected using a six
      camera motion analysis system. A 13-segment biomechanical model was used to
      compute whole body center of mass motion and velocity. FINDINGS: Walking with a
      concurrent cognitive task resulted in significant changes in gait and center of
      mass measurements for both groups. Concussed subjects were found to be able to
      conservatively adjust their whole body center of mass motion to maintain dynamic
      stability while walking without divided attention. However, while walking with
      divided attention, subjects with concussion demonstrated a significantly greater
      medio-lateral center of mass sway. INTERPRETATION: These data suggest that the
      ability to control and maintain stability in the frontal plane during walking is
      diminished under divided attention in individuals following a concussion.

PMID- 15737447
TI  - Changes in knee moments with contralateral versus ipsilateral cane usage in
      females with knee osteoarthritis.
AB  - BACKGROUND: Conservative treatment for osteoarthritis often involves educating
      the patient in methods of decreasing the load transmitted through the diseased
      joint. The use of a cane is one such method and the correct placement of the cane
      with respect to an abnormal knee joint is crucial. The purpose of this study was
      to compare effects on knee moments of force of contralateral versus ipsilateral
      cane usage in female subjects with osteoarthritic knees. METHODS: A convenience
      sample of 14 subjects volunteered for this study. Subjects walked over force
      platforms while ground reaction force and three-dimensional kinematic data were
      captured using a Vicon 370 System. The subjects were tested walking: (a) unaided,
      (b) with ipsilateral cane, and (c) with contralateral cane. Inverse dynamics were
      employed to calculate temporal-spatial, kinematic and kinetic variables.
      Dependent variables included hip and knee frontal plane and sagittal plane
      moments of force, walking speed, cadence and stride length. Repeated measures
      ANOVA assessed differences among walking conditions. FINDINGS: Subjects walked
      significantly faster in the unaided gait condition owing to a higher cadence.
      Ipsilateral cane use resulted in significantly larger hip (versus contralateral
      P=0.018; versus unaided P=0.036) and knee (versus contralateral P=0.043; versus
      unaided P=0.030) frontal plane peak moments during gait. Contralateral cane
      placement was associated with the smallest peak knee abductor (P=<0.001) and
      flexor (P=<0.001) moments. Knee deformity (varus or valgus) did not have any
      significant effect on any variable possibly due to small sample size.
      INTERPRETATION: The results suggest that as is the case for the hip contralateral
      cane placement is the most efficacious for persons with knee osteoarthritis. In
      fact, no cane use may be preferable to ipsilateral cane usage as the latter
      resulted in the highest knee moments of force, a situation which may exacerbate
      pain and deformity.

PMID- 15737448
TI  - The gait initiation process in unilateral lower-limb amputees when stepping up
      and stepping down to a new level.
AB  - BACKGROUND: Unilateral lower-limb amputees lead with their intact limb when
      stepping up and with their prosthesis when stepping down; the gait initiation
      process for the different stepping directions has not previously been
      investigated. METHODS: Ten unilateral amputees (5 transfemoral and 5 transtibial)
      and 8 able-bodied controls performed single steps up and single steps down to a
      new level (73 and 219 mm). Duration, a-p and m-l centre of mass and centre of
      pressure peak displacements and centre of mass peak velocity of the anticipatory
      postural adjustment and step execution phase were evaluated for each stepping
      direction by analysing data collected using a Vicon 3D motion analysis system.
      FINDINGS: There were significant differences (in the phase duration, peak a-p and
      m-l centre of pressure displacement and peak a-p and m-l centre of mass velocity
      at heel-off and at foot-contact) between both amputee sub-groups and controls
      (P<0.05), but not between amputee sub-groups. These group differences were mainly
      a result of amputees adopting a different gait initiation strategy for each
      stepping direction. INTERPRETATION: Findings indicate the gait initiation process
      utilised by lower-limb amputees was dependent on the direction of stepping and
      more particularly by which limb the amputee led with; this suggests that the
      balance and postural control of gait initiation is not governed by a fixed motor
      program, and thus that becoming an amputee will require time and training to
      develop alternative neuromuscular control and coordination strategies. These
      findings should be considered when developing training/rehabilitation programs.

PMID- 15737449
TI  - The effect of cyclic loading on the biomechanical characteristics of the femur
      graft-tibia complex after anterior cruciate ligament reconstruction using Bone
      Mulch screw/WasherLoc fixation.
AB  - BACKGROUND: The Bone Mulch screw/WasherLoc fixation system has attracted notice
      because of its possible advantages. The purpose of the present study was to
      compare the biomechanical properties of this fixation system for the double
      looped flexor tendon graft with those of two standard fixation techniques that
      had been commonly performed in anterior cruciate ligament reconstruction.
      METHODS: Anterior cruciate ligament reconstruction was carried out in each group
      using one of three different procedures (n=14 for each procedure). For each
      group, seven femur-graft-tibia complexes underwent submaximal cyclic displacement
      of 5000 cycles after an initial tension of 20N was applied. Then, tensile testing
      was performed for the complex at a single position, 45 degrees of knee flexion,
      in which the longitudinal axis of the graft coincided with the axis of the bone
      tunnels. The remaining seven complexes in each group were examined in the same
      tensile test without applying any cyclic displacement. FINDINGS: At the 5000th
      cycle of the displacement, the peak load of the complex with the Bone Mulch
      screw/WasherLoc system was significantly higher than that with the Endobutton
      technique (P<0.0001). After 5000 cycles of displacement, the initial stiffness
      and the linear stiffness of the complex with the Bone Mulch screw/WasherLoc
      system were significantly higher than those with the double-looped tendon graft
      and the Endobutton technique (P<0.0001 for both comparisons), while those with
      the Bone Mulch screw/WasherLoc system were significantly lower than those with
      the patellar tendon graft with interference screws (initial stiffness: P=0.0004,
      linear stiffness: P=0.0007). INTERPRETATION: The present study has clarified that
      the Bone Mulch screw/WasherLoc system provides high stiffness to the complex for
      the double-looped flexor tendon graft.

PMID- 15737450
TI  - Measurement of the tensile forces during bone lengthening.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of
      lengthening frequency on mechanical environment in limb lengthening. METHODS:
      Tensile forces were continuously monitored using a load sensor attached to a
      unilateral external fixator. Twenty patients were monitored. Ten patients were
      with acquired femoral shortening, and five of them underwent quasi-continuous
      lengthening of 1440 steps per day, and the other five received step lengthening
      twice a day. The other 10 patients were with achondropalsia. Five of them
      underwent the same quasi-continuous lengthening, and the other five received the
      same step lengthening. The circadian change and the daily course of the tensile
      forces were assessed and compared between quasi-continuous lengthening and step
      lengthening. FINDINGS: As for circadian change, an acute increase in the force
      took place simultaneously with each step of lengthening in the step-lengthening
      group, but very little change of the baseline force level was seen during quasi
      continuous lengthening. As for daily course of the tensile force, it increased
      almost linearly in both lengthening frequency groups in the initial stage of
      lengthening. No significant difference of the average force increment rate in
      this phase was recognized between the quasi-continuous and step lengthening
      groups irrespective of the etiologies. INTERPRETATION: The lengthening frequency
      greatly affected the circadian change of the tensile force, but did not affect
      the increment rate of the force in the linear phase.

PMID- 15737452
TI  - Effects of the posterior cruciate ligament reconstruction on the biomechanics of
      the knee joint: a finite element analysis.
AB  - BACKGROUND: Previous experimental studies have been conducted to evaluate the
      biomechanical effects of posterior cruciate ligament reconstruction; but no
      consensus has been reached on the preferred method of reconstruction. METHODS:
      The 3D finite element mesh of a knee joint was reconstructed from computed
      tomography and magnetic resonance images. The ligaments were considered as
      hyperelastic materials. The tibiofemoral and patellofemoral joints were modeled
      with large sliding contact elements. The 3D model was used to simulate knee
      flexion from 0 degrees to 90 degrees in four cases: a knee with a "native"
      posterior cruciate ligament, a resected posterior cruciate ligament, a
      reconstructed single graft posterior cruciate ligament, and a reconstructed
      double graft posterior cruciate ligament. FINDINGS: A resected posterior cruciate
      ligament induced high compressive forces in the medial tibiofemoral and
      patellofemoral compartments. The pressures generated in the tibiofemoral and
      patellofemoral compartments were nearly the same for the two reconstruction
      techniques (single graft and double graft). The single graft resulted in lower
      tensile stresses inside the graft than for the double graft. INTERPRETATION:
      Firstly, a resected posterior cruciate ligament should be replaced to avoid
      excessive compressive forces, which are a source of cartilage degeneration.
      Secondly, the two types of posterior cruciate ligament reconstruction techniques
      partially restored the biomechanics of the knee in flexion, e.g. contact
      pressures were restored for pure flexion of the knee. The reconstruction
      techniques therefore partially restore the biomechanics of the knee in flexion. A
      double graft reconstruction is subjected to the highest tensile stresses.

PMID- 15737451
TI  - A biomechanical comparison between the single-axis and multi-axis total knee
      arthroplasty systems for the stand-to-sit movement.
AB  - BACKGROUND: Compared to the design of a traditional multi-axis total knee
      arthroplasty, the single-axis arthroplasty studied has a fixed flexion/extension
      center of rotation in the femoral component. The influence of this characteristic
      on functional daily activity, i.e., stand-to-sit, is not well understood. The
      purpose of this study was to investigate the effect of different arthroplasty
      designs on knee kinematic and lower limb muscular activation for the stand-to-sit
      movement. METHODS: Sixteen unilateral, posterior-stabilized knee arthroplasty
      participants (8 single-axis and 8 multi-axis) with excellent Knee Society scores
      performed 4 trials of the stand-to-sit test. Three-dimensional video analysis of
      whole body and joint kinematics and electromyography analysis of quadriceps and
      hamstrings were conducted. One-way ANOVAs were used for statistical analyses
      (alpha=0.05). FINDINGS: The multi-axis group showed some functional adaptations
      while sitting down. The single-axis group exhibited less arthroplasty limb
      quadriceps electromyography and hamstring co-activation electromyography than the
      multi-axis group. For the arthroplasty limb, single-axis demonstrated less
      abduction angular displacement and reached peak abduction earlier than the multi
      axis arthroplasty limb. The estimated effect size for this study was 0.196.
      INTERPRETATION: The single-axis design requires less eccentric knee extensor
      muscle activation and exhibits greater medio-lateral stability than the multi
      axis designs. Findings from this study could provide useful information to
      orthopedic knee surgeons and rehabilitative specialists.

PMID- 15737453
TI  - Tibial torsion measurement by surface curvature.
AB  - BACKGROUND: Tibial torsion is the angle between the transverse axes of the
      proximal and distal tibial articular surfaces. It measures the degree of twisting
      of the tibia around its own longitudinal axis. The accurate measurement on the
      magnitude of tibial torsion is of great use in monitoring derangements. It is
      also useful as a baseline in the event of surgical intervention. Various methods
      have been developed but none of them have gained wide acceptance. Even the CT
      scan technique, which is considered the "gold standard", produces varying results
      when executed by different researchers. A quick, objective and non-invasive
      method is thus very much needed for the effective monitoring of tibial torsion in
      clinical environments. METHODS: Eighteen adult men's lower legs were scanned by a
      laser scanner to give the surface coordinates of the leg surfaces. By calculating
      curvature maps of legs from the 3D coordinates, stable anatomical landmarks such
      as the lateral and medial malleoli can be located. The angle indicating the
      degree of tibial torsion can then be derived from these landmarks. FINDINGS: The
      objective determination of the various anatomical landmarks results in a
      reproducible measure of tibial torsion. The results obtained in this study are
      generally in agreement with the measurements reported previously. INTERPRETATION:
      The reproducibility of the results allows for the objective observation,
      monitoring and comparison of tibial torsion over time and across subjects. It
      allows also for the development of a system of measurement that is fast,
      convenient, accurate and radiation-free.

PMID- 15737454
TI  - Trichloroethylene (TCE) removal in a single pulse suspension bioreactor.
AB  - This work describes TCE biotic removal in a single-pulse bioreactor under aerobic
      conditions. Activated sludge from a wastewater-treatment plant was used for
      inoculation of the cultivator. The experiment focused on a more detailed
      verification of microbial composition of mixed heterotrophic culture during
      pulsed phenol dosage. Attention was given to suppressing eucaryotic organisms,
      particularly yeasts and fungi, by the addition of cycloheximide. The TCE-removal
      capacity of the heterotrophic culture, described by kinetic tests, was dependent
      on pulsed phenol injection and on cyclic addition of phenol and TCE. Maximum TCE
      degradation was determined in a batch test. It was found that the addition of
      cycloheximide (an antibiotic against propagation and growth of fungi and yeast)
      increased the TCE degradation activity of the mixed microbial suspension. A
      certain residual amount of TCE remained in some of the experiments.

PMID- 15737455
TI  - The consequences of land use change on nutrient exports: a regional scale
      assessment in south-west Victoria, Australia.
AB  - Estimation of nutrient load production based on multi-temporal remotely sensed
      land use data for the Glenelg-Hopkins region in south-west Victoria, Australia,
      is discussed. Changes in land use were mapped using archived Landsat data and
      computerised classification techniques. Land use change has been rapid in recent
      history with 16% of the region transformed in the last 22 years. Total nitrogen
      and phosphorus loads were estimated using an export coefficient model. The
      analysis demonstrates an increase in modelled nitrogen and phosphorus loadings
      from 1980 to 2002. Whilst such increases were suspected from past anecdotal and
      ad-hoc evidence, our modelling estimated the magnitude of such increases and thus
      demonstrated the enormous potential of using remote sensing and GIS for
      monitoring regional scale environmental processes.

PMID- 15737456
TI  - Methanogenic toxicity and continuous anaerobic treatment of wood processing
      effluents.
AB  - Wood processing effluents contain different types of phenolic compounds, from
      simple monomers to high molecular weight (MW) polyphenolic polymers, that can
      inhibit wastewater treatment. This work presents a comparative study of the
      methanogenic toxicity produced by three wood processing effluents (hardboard,
      fiberboard and BKME (kraft mill effluent)) using Pinus radiata, Eucalyptus and
      Tepa as feedstock (the last one being a native Chilean tree species). This study
      evaluates the influence of non-adapted granular and adapted flocculent sludge on
      forest industrial wastewater treatment as well as continuous anaerobic
      biodegradation of hardboard processing effluent using the upflow anaerobic sludge
      blanket (UASB). The adapted biomass (flocculent sludge) did not show any lag
      phase signs. The 50% IC (the concentration causing 50% inhibition of methanogenic
      activity) was 4.3 g COD-effluent (chemical oxygen demand (COD)-of the effluent)/l
      and 2.8 g COD-effluent/l for the flocculent sludge and the granular sludge,
      respectively. The UASB system worked at low organic load rates (0.1-0.4 g COD/l
      d) with the COD removal ranging between 10 and 30%, and color removal did not
      occur under anaerobic conditions due to high MW. Indeed, the MW analysis
      indicates the presence of phenolic compounds over 25,000 Da in the anaerobic
      effluent.

PMID- 15737457
TI  - Ecological modeling for water quality management of Kwangyang Bay, Korea.
AB  - This study estimated the appropriate pollutant load reduction from point sources
      in Kwangyang Bay, Korea, using an eco-hydrodynamic model. The total chemical
      oxygen demand (COD), nitrogen (TN), and phosphorus (TP) loads from rivers and
      ditches that provide input to the bay were approximately 2.8x10(4), 2.5x10(4),
      and 5.9x10(2) kg day-1, respectively. Wastewater discharge from industrial
      complexes was the greatest contributor to pollutant loads in the inner part of
      the bay. COD values in the inner part of the bay were greater than 3.0 mg l-1,
      and exceeded Korean seawater quality grade III limits. A residual current was
      simulated, using a hydrodynamic model, to have a slightly complicated pattern in
      the inner part of the bay, ranging from 0.001 to 8 cm s-1. In the outer part of
      the bay, the simulated current flowed out to the South Sea with a southward flow
      at a maximum of 15 cm s-1. The results of the ecological model simulation of COD
      levels showed high concentrations, exceeding 4 mg l-1, in the southwest of the
      Myodo, an area of wastewater discharge, and lower levels, approaching less than 1
      mg l-1, closer to the outer part of the bay. Engineering countermeasures to
      reduce the organic and inorganic material loads from point sources by more than
      45% were required to keep the COD levels below 2 mg l-1.

PMID- 15737458
TI  - The effect of olive mill wastewater on seed germination after various
      pretreatment techniques.
AB  - Olive mill wastewater (OMW) management has been a major issue of environmental
      concern for olive oil producing countries. OMW can be a serious nuisance, when
      disposed of untreated, due to its significantly high organic load, its phytotoxic
      properties and its relatively low biodegradability. Field and plant irrigation
      with raw or pretreated OMW is an easy and relatively inexpensive method to treat
      and dispose of OMW. Typical pretreatment techniques could be comprised of phase
      separation through a settling basin, dilution with water, aeration to promote
      biological degradation and pH neutralization. A full factorial experimental
      design approach was used here to study the main effects and interactions of the
      above four pretreatment techniques on the germination of tomato and chicory
      seeds. Results of the study showed that the most statistically significant
      technique affecting OMW phytotoxicity is water dilution. The next most
      significant technique was aeration. In particular, phytotoxicity decreased with
      increased OMW dilution with water, when OMW was aerated and without pH
      adjustment. pH neutralization resulted in increased phytotoxicity. Settling did
      not significantly decrease the phytotoxicity of settled OMW and is therefore not
      considered necessary in an OMW management system in which plant irrigation is the
      goal. The interaction of aeration and pH was, marginally, the most significant
      two-way interaction for tomato seeds, while no interactions were significant when
      chicory seeds were used.

PMID- 15737459
TI  - Chemometrical exploration of the wet precipitation chemistry from the Austrian
      Monitoring Network (1988-1999).
AB  - The present paper deals with the application of different chemometric methods to
      an environmental data set derived from the monitoring of wet precipitation in
      Austria (1988-1999). These methods are: principal component analysis (PCA);
      projection pursuit (PP); density-based spatial clustering of application with
      noise (DBSCAN); ordering points to identify the clustering structures (OPTICS);
      self-organizing maps (SOM), also called the Kohonen network; and the neural gas
      (NG) network. The aim of the study is to introduce some new approaches into
      environmetrics and to compare their usefulness with already existing techniques
      for the classification and interpretation of environmental data. The density
      based approaches give information about the occurrence of natural clusters in the
      studied data set, which, however, do not occur in the case presented here;
      information about high-density zones (very similar samples) and extreme samples
      is also obtained. The partitioning techniques (clustering, but also neural gas
      and Kohonen networks) offer an opportunity to classify the objects of interest
      into several defined groups, the patterns of ionic concentration of which can be
      studied in detail. The visual aids, such as the color map and the Kohonen map,
      for each site are very helpful in understanding the relationships between samples
      and between samples and variables. All methods, and in particular projection
      pursuit, give information about samples with extreme characteristics.

PMID- 15737460
TI  - Multi-criteria decision analysis for the optimal management of nitrate
      contamination of aquifers.
AB  - We present an integrated methodology for the optimal management of nitrate
      contamination of ground water combining environmental assessment and economic
      cost evaluation through multi-criteria decision analysis. The proposed
      methodology incorporates an integrated physical modeling framework accounting for
      on-ground nitrogen loading and losses, soil nitrogen dynamics, and fate and
      transport of nitrate in ground water to compute the sustainable on-ground
      nitrogen loading such that the maximum contaminant level is not violated. A
      number of protection alternatives to stipulate the predicted sustainable on
      ground nitrogen loading are evaluated using the decision analysis that employs
      the importance order of criteria approach for ranking and selection of the
      protection alternatives. The methodology was successfully demonstrated for the
      Sumas-Blaine aquifer in Washington State. The results showed the importance of
      using this integrated approach which predicts the sustainable on-ground nitrogen
      loadings and provides an insight into the economic consequences generated in
      satisfying the environmental constraints. The results also show that the proposed
      decision analysis framework, within certain limitations, is effective when
      selecting alternatives with competing demands.

PMID- 15737461
TI  - Discussion of the paper "Cost effective policies for alternative distributions of
      stochastic water pollution" by Gren, Destouni and Tempone.
AB  - This discussion addresses some aspects of a recent paper appearing in this
      journal which investigates cost effective coastal water management based on
      different assumptions of the probability distributions (normal and log-normal) of
      pollutant transport. We also suggest an alternative approach to overcome the
      technical problems of using the theoretical correct distribution for
      characterising environmental data (log-normal) within a probabilistic programming
      framework.

PMID- 15737463
TI  - Stimulated resistin expression in white adipose of rats with bile duct ligation
      induced liver cirrhosis: relationship to cirrhotic hyperinsulinemia and increased
      tumor necrosis factor-alpha.
AB  - Resistin, an adipose-derived polypeptide hormone, is proposed as a candidate of
      insulin resistance, although its roles in inhibiting adipogenesis and in
      inflammation have also been suggested. Liver cirrhosis is characterized by
      elevated circulating proinflammatory cytokines, including tumor necrosis factor
      alpha (TNF-alpha), hyperinsulinemia and insulin resistance. The study aimed to
      examine resistin expression and its association with insulin and TNF-alpha in a
      cirrhotic rat model using bile duct ligation (BDL). The BDL-induced cirrhotic
      rats showed significantly lower fat mass, insulin sensitivity and elevated plasma
      insulin and TNF-alpha compared to sham animals. In addition, epididymal TNF-alpha
      and resistin mRNA and protein levels were higher in cirrhotic rats. In normal
      control rats, in vivo insulin infusion and ex vivo administration of TNF-alpha to
      cultured fat pads increased resistin gene expression significantly. These results
      implied that hyperinsulinemia and increased TNF-alpha levels might upregulate
      adipose resistin gene in BDL-induced liver cirrhosis. Further study is necessary
      to document the role of resistin in metabolic abnormalities of liver cirrhosis.

PMID- 15737464
TI  - Prolactin-induced expression of vascular endothelial growth factor via Egr-1.
AB  - Angiogenesis is a dynamic process regulated by both local and systemic factors.
      Among these is vascular endothelial growth factor (VEGF), a potent effector of
      angiogenesis and vascular permeability. Previously we showed that VEGF is
      temporally and spatially regulated in the mouse mammary gland during development
      and lactation. Given the functions of prolactin (PRL) during these stages and the
      supporting role of the vasculature, we investigated the regulation of VEGF by
      PRL. Treatment of HC11 mouse mammary epithelial and Nb2 rat lymphoma cells with
      PRL induced VEGF expression. Deletion and mutation analysis identified a GC-rich
      region in the proximal region of the VEGF promoter that constitutively bound Sp1
      and PRL-induced Egr-1. These sites conferred PRL-responsiveness leading to
      increased VEGF transcription. The induction of VEGF by PRL was PRL receptor-,
      Jak2- and MAP kinase kinase-dependent. Our results indicate that PRL induces VEGF
      expression through Egr-1, and implicates VEGF as an intermediary of PRL-regulated
      angiogenesis.

PMID- 15737465
TI  - Activin A inhibits differentiation of 3T3-L1 preadipocyte.
AB  - We investigated the effect of activin A on differentiation of 3T3-L1
      preadipocyte. Activin A suppressed the induction of terminal differentiation
      markers such as glycerol-3-phosphate dehydrogenase (GPDH) activity, lipid
      accumulation, and the expression of adipocyte fatty acid-binding protein (aP2)
      mRNA when the cells were treated with activin A throughout the differentiation
      period. Activin A treatment during the early phase decreased GPDH activity and
      aP2 mRNA level, and also reduced the expression of peroxisome proliferator
      activated receptor (PPAR) gamma and CCAAT/enhancer binding protein (C/EBP) alpha
      mRNAs without affecting the expressions of the active isoforms of C/EBPbeta and
      its mRNA. On the other hand, activin A treatment had no effect on the mitotic
      clonal expansion. These results indicate that activin A inhibits adipogenesis via
      affecting the transcriptional factor cascade upstream of PPARgamma expression.

PMID- 15737466
TI  - Leptin receptors are down-regulated in uterine implantation sites compared to
      interimplantation sites.
AB  - Leptin is a circulating hormone that plays an important role in the regulation of
      metabolism, obesity, and reproduction. Leptin binds to its receptors on the cell
      membrane and is involved in the activation of STAT3. Recently, endometrium was
      suggested to be a novel target for leptin recently. We, therefore, examined the
      expression of leptin, leptin receptors, and STAT3 in the mouse uterus
      (implantation and interimplantation sites) to investigate the role of the leptin
      system during the early implantation period. Leptin mRNA was not detected in
      mouse uterine tissues or blastocysts, although adipose tissue, the positive
      control, showed a strong signal. Both of the receptor splice variants were
      expressed in the uterus and blastocysts, but the mRNA level was much lower in
      implantation sites compared to interimplantation sites. The mRNA expression of
      leptin receptors was determined to be higher in stromal cells than in the luminal
      epithelium using laser capture microdissection (LCM) analysis. Using
      immunohistochemistry, leptin was detected as a strong signal in the luminal
      epithelium and embryo, whereas the receptor was detected in subepithelial stromal
      cells rather than the luminal epithelium. As leptin itself was not detected by RT
      PCR, the immunohistologically detected leptin may originate elsewhere, such as in
      adipose tissue. The differential expression of leptin receptors in implantation
      sites compared to interimplantation sites suggests that the leptin/leptin
      receptor system may be a delicate regulator of the implantation process.

PMID- 15737467
TI  - GLUT4 expression in 3T3-L1 adipocytes is repressed by proteasome inhibition, but
      not by inhibition of calpains.
AB  - Because of recent studies showing linkage of type 2 diabetes with the calpain 10
      gene, we investigated the ability of calpains to regulate GLUT4 expression in 3T3
      L1 adipocytes. Treatment of 3T3-L1 adipocytes with the calpain inhibitor ALLN
      significantly decreased the mRNA and protein expression of GLUT4. GLUT4
      expression was not affected by treatment with the more selective calpain
      inhibitors PD150606, calpeptin, or a calpastatin peptide. In contrast, treatment
      with the proteasome inhibitors lactacystin or MG132 repressed GLUT4 mRNA level to
      35% (10 microM lactacystin) and 12% (10 microM MG132) of control levels.
      Therefore, the expression of GLUT4 in 3T3-L1 adipocytes was repressed by
      proteasome inhibition, but not by inhibition of calpains; the effect of ALLN was
      due to its ability to inhibit proteasome function, rather than its action to
      inhibit calpains. Concomitant with the repression of GLUT4 mRNA levels,
      proteasome inhibition decreased GLUT4 protein levels in 3T3-L1 adipocytes. The
      decrease in GLUT4 expression occurred at the transcriptional level, as treatment
      with proteasome inhibitors decreased GLUT4 transcription measured by a nuclear
      run-on assay. Thus, these data demonstrate a new pathway for the regulation of
      GLUT4 expression that involves proteasomal degradation of factors that regulate
      GLUT4 expression.

PMID- 15737468
TI  - Genetic analysis of bovine viral diarrhoea viruses from Australia.
AB  - Eighty-nine bovine viral diarrhoea viruses (BVDV) from Australia have been
      genetically typed by sequencing of the 5' untranslated region (5'-UTR) and for
      selected isolates the N(pro) region of the viral genome. Phylogenetic
      reconstructions indicated that all of the samples examined clustered within the
      BVDV type 1 genotype. Of the 11 previously described genetic groups of BVDV-1, 87
      of the samples examined in this study clustered with the BVDV-1c, while two
      samples clustered with the BVDV-1a. Based on these analyses there appears to be
      limited genetic variation within the Australian BVDV field isolates. In addition,
      the phylogenetic reconstructions indicate that the clustering of Australian BVDV
      in the phylogenetic trees is not a result of geographic isolation.

PMID- 15737469
TI  - Genomic sequences of low-virulence avian paramyxovirus-1 (Newcastle disease
      virus) isolates obtained from live-bird markets in North America not related to
      commonly utilized commercial vaccine strains.
AB  - Avian paramyxovirus 1 (APMV-1), also referred to as Newcastle disease virus
      (NDV), variants of low virulence were isolated from chickens, ducks and other
      unidentified species found in live-bird markets of the northeastern United
      States. These isolates were characterized as APMV-1 by the hemagglutination
      inhibition (HI) assay utilizing NDV-specific polyclonal antisera. However, the
      isolates failed to react with a monoclonal antibody that has specificity for a
      wide variety of APMV-1 isolates. Although only highly virulent isolates require
      reporting to international regulatory agencies, the ability to correctly identify
      APMV-1 types is important for control and regulatory purposes. Protein gel
      patterns of the purified isolates resembled previously reported APMV-1 and anti
      NDV polyclonal sera recognized the viral proteins. For three isolates
      oligonucleotide primers specific for the nucleoprotein, fusion protein and
      polymerase genes of NDV were utilized to synthesize cDNA using viral RNA as a
      template. Approximately 12kb of the genome was subsequently sequenced for the
      three isolates that included the nucleoprotein, phosphoprotein, matrix protein,
      fusion (F) protein, hemagglutinin-neuraminidase protein genes and a 5' portion of
      the polymerase gene. The isolates had an F protein cleavage site sequence of
      ERQER/LVG indicating low-virulence viruses that phylogenetically separated with
      other unique NDV isolates designated as a lineage 6 genotype. Additionally, a
      four amino acid insert was detected in the predicted phosphoprotein which
      complies with the "rule of six" among paramyxoviruses. These APMV-1 genotypes
      have not been previously reported in North America and further substantiate the
      heterogeneous genetic nature of these commercially important pathogens found
      worldwide.

PMID- 15737470
TI  - Immunisation with a combination of two complementary feline calicivirus strains
      induces a broad cross-protection against heterologous challenges.
AB  - Feline calicivirus (FCV) is characterised by a high degree of antigenic variation
      potentially compromising vaccine efficacy. Inclusion of several FCV strains or
      antigens in current vaccines could be a means to improve protection against
      antigenically distinct isolates. This study evaluated the synergy between two FCV
      strains (FCVG1 and FCV431) by comparing immunity induced by either strain with
      that provided by a combination of the two strains against an heterologous
      challenge with antigenically distant FCV strains (FCV393 and FCV220). Thirty-two
      SPF kittens were randomly allocated to four groups of eight cats in each group.
      Groups B, C and D cats were vaccinated once subcutaneously with strains FCVG1,
      FCV431, and FCVG1 + FCV431, respectively. Each kitten received a total dose of
      10(3.4) CCID50 of FCV. Control group A was not immunised. On day 31, four cats
      from each group were challenged oronasally with FCV220 and four cats with FCV393.
      Following challenge, the cats were monitored for clinical signs, viral shedding
      and antibody responses. FCV220 and FCV393 induced severe clinical signs in
      control cats typical of FCV infection. Immunisation with both strains mixed
      together induced higher neutralizing antibody titres against FCV220 and FCV393
      strains on average. Protection was observed in all groups, however combination of
      the two strains resulted in a better clinical protection and reduction of virus
      shedding after heterologous challenge. A moderate correlation was observed
      between neutralizing antibody titres at the time of challenge and protection
      against clinical signs. These results indicated that vaccines combining antigens
      from different FCV strains may induce a broader heterologous protection.

PMID- 15737471
TI  - Mutations in feline immunodeficiency (FIV) virus envelope gene V3-V5 regions in
      FIV-infected cats.
AB  - The envelope (Env) gene V3-V5 regions of the feline immunodeficiency virus (FIV)
      encode the neutralizing epitopes. Since mutations in these regions induce
      resistance to viral neutralizing antibodies, they may influence the effects of
      vaccines. To examine the in vivo mutation rate in these regions, we cloned cDNA
      for the Env gene V3-V5 regions from the PBMC of experimentally FIV-infected cats,
      and compared the deduced amino acid sequences. Blood or plasma from an FIV
      Shizuoka strain-infected cat was inoculated into a second group of SPF cats, and
      their blood or plasma was inoculated into the third group. The amino acid
      sequence encoded by the viral gene of the first cat was compared with those
      encoded by the viral genes of a total of eight cats in the second and third
      groups (two and six cats, respectively). The amino acid sequences in two cats in
      the second and third groups were 100% homologous and in one cat in the third
      group was 98.3% homologous to that in the first infected cat. Five cats had the
      same sequence, which was 97.8% homologous to that in the first infected cat.
      Three kittens, born 2 months after the inoculation of the FIV Aomori-2 strain
      into the mother cat, were anti-FIV negative at 4 weeks after birth, but became
      seropositive at 33 weeks after birth, confirming FIV infection. Comparison of the
      encoded amino acid sequences of the viral gene in two cats at 48 weeks after
      birth showed 100% homology to that of the virus inoculated into the mother cat,
      and the remaining one cat had a single residue substitution, resulting in 99.4%
      homology. These results suggest that the FIV Env gene V3-V5 regions are stably
      maintained for at least 1-2 years after infection.

PMID- 15737472
TI  - Relationship of bovine viral diarrhea virus persistent infection to incidence of
      diseases on dairy farms based on bulk tank milk test by RT-PCR.
AB  - The prevalence of bovine viral diarrhea virus (BVDV) in dairy herds in Hokkaido,
      Japan, was estimated by reverse transcription polymerase chain reaction (RT-PCR)
      using bulk tank milk samples. Sixteen out of 265 dairy herds were identified as
      BVDV positive, and at least one persistently infected (PI) cattle was recognized
      in each of the positive herds except for two herds of which, owners did not agree
      to examine individual cows. The proportion of positive herds with a history of
      BVDV PI was significantly higher than that with no history of BVDV PI (odds ratio
      (OR) 4.25, 95% confidence interval (CI) 1.471-12.278, p = 0.004). The herds
      examined for BVDV were divided into two groups, high and low disease incidence
      groups based on the occurrence of diseases such as diarrhea, pneumonia or
      abortion in the past 1 year. The BVDV positive herds in the high disease
      incidence group were significantly more than that in the low disease incidence
      group (OR 2.92, CI 1.110-7.683, p = 0.024). It was observed that there were
      significantly (p = 0.008) more PI calves or heifers in farms of high disease
      incidence group than in farms of low disease incidence group. These results
      suggested that bulk tank milk test was available method for the detection of PI
      animals in dairy herds, and the existence of PI non-lactating cows in herd
      correlated with the incidence of diseases of the diarrhea or respiratory
      disorders.

PMID- 15737474
TI  - Production of bacteriocins by coagulase-negative staphylococci involved in bovine
      mastitis.
AB  - In the present study, 188 coagulase-negative Staphylococcus (CNS) strains were
      isolated from bovine mastitis cases from 56 different Brazilian dairy herds,
      located in the Southeast region of the country, and were tested for antimicrobial
      substance production. Twelve CNS strains (6.4%) exhibited antagonistic activity
      against a Corynebacterium fimi indicator strain. Most antimicrobial substances
      were sensitive to proteolytic enzymes suggesting that they might be bacteriocins
      (Bac). Amongst the CNS producers, six were identified as S. epidermidis, two as
      S. simulans, two as S. saprophyticus, one as S. hominis and one as S. arlettae.
      Plasmid profile analysis of these strains revealed the presence of at least one
      plasmid. The Bac(+) strains presented either no or few antibiotic resistance
      phenotypes. Three strains were shown to produce a bacteriocin either identical or
      similar to aureocin A70, a bacteriocin previously isolated from an S. aureus
      strain isolated from food. The remaining Bac(+) strains produce antimicrobial
      peptides that seem to be distinct from the best characterised staphylococcal
      bacteriocins described so far. Some of them were able to inhibit Listeria
      monocytogenes, an important food-borne pathogen, and several strains of
      Streptococcus agalactiae associated with bovine mastitis, suggesting a potential
      use of these bacteriocins either in the prevention or in the treatment of
      streptococcal mastitis.

PMID- 15737473
TI  - Experimental reproduction of postweaning multisystemic wasting syndrome (PMWS) in
      pigs in Sweden and Denmark with a Swedish isolate of porcine circovirus type 2.
AB  - An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets
      co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is
      at present one of the best methods to study factors affecting development of
      postweaning multisystemic wasting syndrome (PMWS). A Swedish isolate of PCV2 (S
      PCV2) retrieved in 1993 from a healthy pig has been used in this model to
      reproduce PMWS in pigs from Northern Ireland. This virus has been present in the
      Swedish pig population for at least a decade without causing any known PMWS
      disease problems, despite its potential pathogenicity. The reasons for this are
      unknown, but could be related to genetics, absence of triggers for PCV2
      upregulation (infectious agent and/or management forms) within Swedish pig
      husbandry. In order to confirm the pathogenicity of S-PCV2, Swedish and Danish
      pigs were experimentally infected with this isolate according to the established
      model. Swedish pigs were also infected with a reference isolate of PCV2 (PCV2
      1010) to compare the severity of disease caused by the two isolates in Swedish
      pigs. Both Danish and Swedish pigs developed PMWS after the experimental
      infection with S-PCV2. Antibodies to PCV2 developed later and reached lower
      levels in serum from pigs infected with S-PCV2 than in pigs inoculated with PCV2
      1010. In general, pigs infected with S-PCV2 showed more severe clinical signs of
      disease than pigs infected with PCV2-1010, but pigs from all PCV2-inoculated
      groups displayed gross and histological lesions consistent with PMWS. All pigs
      inoculated with PPV, alone or in combination with PCV2, displayed interleukin-10
      responses in serum while only pigs infected with PPV in combination with PCV2
      showed interferon-alpha in serum on repeated occasions. Thus, the pathogenicity
      of S-PCV2 was confirmed and a role for cytokines in the etiology of PMWS was
      indicated.

PMID- 15737476
TI  - Feline uropathogenic Escherichia coli from Great Britain and New Zealand have
      dissimilar virulence factor genotypes.
AB  - We investigated the prevalence of 30 known virulence factor genes (VFGs) in
      uropathogenic E. coli (UPEC) from two geographically distinct feline populations,
      using a PCR-based approach. E. coli isolates were also subjected to
      macrorestriction analysis to assess their phylogenetic relationships. VFG
      profiles differed considerably according to the geographic origin of the
      isolates, enabling discriminant analysis to correctly predict population
      membership for 15/15 NZ isolates and 18/22 UK isolates. The prevalence of gene
      markers for P-fimbriae (PapA, PapC, PapEF, and PapG III), colicin V (CvaC),
      increased serum survival factor (Iss), complement resistance factor (TraT),
      pathogenicity-associated island (MalX), iron-regulated siderophore receptor
      (IreA) and haemolysin (HlyD) differed significantly between UK and NZ isolates.
      Significant phylogenetic differences between the two populations were also
      identified, but VFG profiles could not be predicted on the basis of phylogenetic
      relationships. Consequently, a geographically uneven distribution of certain
      virulence genes, independent of phylogeny, is the likely cause of VFG differences
      between populations. We cannot rule out that subtle differences in patient
      disease status may have contributed to the dissimilarity of VFG profiles.

PMID- 15737475
TI  - Evaluation of the antimicrobial activity of florfenicol against bacteria isolated
      from bovine and porcine respiratory disease.
AB  - Antimicrobial susceptibility of florfenicol (FFC) against 243 bacterial agents
      isolated in Korea from cattle and pigs with respiratory disease were investigated
      by agar diffusion and microdilution broth methods following the recommendations
      provided by the National Committee for Clinical Laboratory Standards. All
      Actinobacillus pleuropnemoniae, Pasteurella multocida, Mannheimia haemolytica and
      98.6% of the Bordetella bronchiseptica isolates were susceptible to FFC, which as
      significantly more effective than the other antibiotics used in this study. FFC
      also showed high in vitro antimicrobial activities (MIC(90) < or = 1 microg/ml)
      against all strains tested with a minimal inhibitory concentration (MIC)
      determination ranging from 0.12 to 4 microg/ml. No resistant strains of A.
      pleuropneumoniae, P. multocida and M. haemolytica to FFC have apparently
      developed since the first introduction of this antibiotics for veterinary use in
      Korea. The results suggest that FFC is therapeutically valuable in the treatment
      of primary or complicating bacterial pathogens causing of the bovine and swine
      respiratory tract.

PMID- 15737477
TI  - Investigation of domestic animals and pets as a reservoir for intimin- (eae) gene
      positive Escherichia coli types.
AB  - Domestic animals belonging to seven different species (cattle, sheep, dogs, cats,
      pigs, chicken and goats) were investigated as natural reservoirs for attaching
      and effacing Escherichia coli (AEEC). For this, 2165 E. coli strains from faeces
      of 803 animals were examined for the presence of the intimin -(eae) gene as a
      characteristic of AEEC strains. Ten percent of the animals were found to excrete
      AEEC, most frequently found in sheep (19.2%) and pigs (17.6), followed by cattle
      (10.4%), dogs (7.2%), cats (6.5%) and poultry (2.3%). The 97 AEEC strains from
      animals were grouped into 44 serotypes. Only four E. coli serotypes (O2:H8,
      O26:[H11], O109:[H25] and O145:[H28] were found in more than one animal host
      species. AEEC O26:[H11] strains were most frequently isolated (13.4%) being
      present in cattle, poultry, pigs and sheep. A search for virulence markers
      associated with enterohemorrhagic E. coli (EHEC) revealed Shiga-toxin genes in
      three (3.1%) AEEC strains from sheep. Bundle forming pili genes as a trait of
      typical enteropathogenic E. coli (EPEC) were detected in four (4.1%) strains from
      dogs and cats. The remaining 90 AEEC strains were classified as atypical EPEC.
      Typing of intimin genes revealed intimin beta being present in 51.5% of the
      strains, followed by intimins theta (23.7%), epsilon (6.2%), kappa (5.2%), zeta
      (5.2%), alpha, eta and iota (each 1.0%). Our data indicate that domestic animals
      and pets constitute an important natural reservoir of AEEC strains, and some of
      these (O26:[H11], O103:H2, O128:H2, O145:[H28] and O177:[H11]) are known to occur
      as pathogens in humans.

PMID- 15737478
TI  - Comparison of phenotypic and genotypic detection of penicillin G resistance of
      Staphylococcus aureus isolated from bovine intramammary infection.
AB  - Resistance of Staphylococcus aureus to penicillin G is common among isolates from
      bovine mastitis. We determined phenotypic resistance to penicillin G for 151 S.
      aureus isolates derived from dairy cows with intramammary infection by two
      methods. The methods were determination of minimum inhibitory concentration (MIC)
      by a standard agar dilution technique and direct testing of beta-lactamase
      production using a chromogenic cephalosporin, nitrocefin. The results from these
      tests were compared with the presence of the beta-lactamase (blaZ) gene in the
      isolates, which was detected by polymerase chain reaction (PCR). Testing beta
      lactamase production with nitrocefin was more predictive for the presence of the
      blaZ gene than the agar dilution method and the results of the former agreed
      highly with the presence of the blaZ gene in the isolates. In contrast, the
      resistance breakpoint generally used in the agar dilution method may be too high
      for prediction of penicillin resistance in S. aureus isolates with borderline
      MICs. Using this method, 40% of the isolates possessing the blaZ gene were
      classified as susceptible; however, majority of these isolates produced beta
      lactamase when tested with nitrocefin.

PMID- 15737479
TI  - Detection of the enterotoxins A, B, and C genes in Staphylococcus aureus from
      goat and bovine mastitis in Brazilian dairy herds.
AB  - To determine the distribution of genes that encode enterotoxins A, B and C, 36
      strains of Staphylococcus aureus isolated from goat mastitis and 64 isolated from
      bovine mastitis were analyzed by Multiplex PCR. Of the total strains studied, 37
      (37%) were detected to have some of the SEs genes. From the bovine mastitis
      strains, 4 (6.3%) co-amplified the sea and seb genes and 2 (3.1%) were positive
      for the sec gene. From the goat mastitis strains, 31 (86%) tested positive to the
      Multiplex, and the sec gene was detected in all of them. The production of SE was
      detected in all strains harboring the corresponding gene. The results
      demonstrated that S. aureus isolated from goat mastitis had a higher
      enterotoxigenic potential than those isolated from bovine mastitis. Additionally,
      the presence of the sec gene in the majority of goat mastitis strains suggests a
      possible involvement of SEC in goat mastitis pathogenesis.

PMID- 15737480
TI  - Genotype dynamics of Campylobacter jejuni in a broiler flock.
AB  - We investigated the genotype diversity and dynamics of Campylobacter in a
      commercial broiler flock during rearing and slaughter. In total, 220
      Campylobacter jejuni isolates collected on four sampling occasions during rearing
      and from routine sampling during slaughter were subtyped by SmaI macrorestriction
      and pulsed-field gel electrophoresis, PFGE. Eight different SmaI types were
      found. During rearing, a subsequent addition of genotypes occurred, with two SmaI
      types found at 2 weeks of age and six types on the day before slaughter. All
      types that were detected in more than one isolate were also found on all
      succeeding sampling occasions, including the slaughter sampling. Two new types
      were found in the slaughter samples. In two-thirds of the individual birds
      sampled the day before slaughter, more than one SmaI type were found, although
      there was a clear tendency for dominance of one type in individual birds. Our
      results show that multiple genotypes of C. jejuni may be present in a commercial
      broiler flock during rearing and even in gastrointestinal tracts of individual
      birds. Both recurring environmental exposure and genetic changes within the
      population may explain the genotype diversity. Although the distribution of
      genotypes varied between different sampling occasions, we found no indication
      that any subtype excluded another during the rearing of the broiler flock.

PMID- 15737481
TI  - Pigmented-anaerobic bacteria associated with canine periodontitis.
AB  - The etiology of human periodontal disease has been the focus of considerable
      research, yet relatively little is known about the causative agents of companion
      animal periodontitis. In humans, Porphyromonas gingivalis, a black-pigmented
      anaerobic bacteria (BPAB), has been implicated as the primary periopathogen. It
      has been demonstrated that BPAB are also found in companion animal periodontal
      pockets. While some animal BPAB have been individually identified, a study to
      identify the most frequently isolated subgingival BPAB has not been completed
      using genetic tools. The objective of this work was to identify the types and
      relative frequencies of pigmented anaerobic bacteria found in the periodontal
      pockets of dogs. Porphyromonas salivosa, Porphyromonas denticanis (a novel
      species) and Porphyromonas gulae were found to be the most frequently isolated
      BPAB associated with canine periodontitis.

PMID- 15737483
TI  - Detection of the esp gene in high-level gentamicin resistant Enterococcus
      faecalis strains from pet animals in Japan.
AB  - We investigated the prevalence of the esp gene and the susceptibility to
      gentamicin in Enterococcus faecalis and E. faecium strains obtained from pet
      animals. Nine of 30 E. faecalis and 2 of 38 E. faecium strains from the pet
      animals had the esp gene. Three esp-positive E. faecalis strains, which were
      isolated from two dogs and a cat, showed gentamicin MICs of > or =256 microg/ml
      and harbored the high-level gentamicin resistance (HLGR) gene, aac(6')-Ie
      aph(2'')-Ia. Of the nine esp-positive E. faecalis strains, five, including the
      three strains with the HLGR gene, were closely related by numerical analysis of
      PFGE patterns. Longitudinal investigation needs to elucidate whether the HLGR
      gene was incorporated into a subpopulation of the esp-positive E. faecalis.

PMID- 15737482
TI  - Persistence of Mycoplasma gallisepticum in chickens after treatment with
      enrofloxacin without development of resistance.
AB  - The ability of the avian pathogen Mycoplasma gallisepticum to persist despite
      fluoroquinolone treatment was investigated in chickens. Groups of specific
      pathogen free chickens were experimentally infected with M. gallisepticum and
      treated with enrofloxacin at increasing concentrations up to the therapeutic
      dose. When M. gallisepticum could no longer be re-isolated from chickens, birds
      were stressed by inoculation of infectious bronchitis virus or avian pneumovirus.
      Although M. gallisepticum could not be cultured from tracheal swabs collected on
      several consecutive sampling days after the end of the enrofloxacin treatments,
      the infection was not eradicated. Viral infections reactivated the mycoplasma
      infection. Mycoplasmas were isolated from tracheal rings cultured for several
      days, suggesting that M. gallisepticum persisted in the trachea despite the
      enrofloxacin treatment. The minimal inhibitory concentration (MIC) of
      enrofloxacin for most of the re-isolated mycoplasmas was the same as that of the
      strain with which the birds were inoculated. Furthermore, no mutation could be
      detected in the fluoroquinolone target genes. These results suggest that M.
      gallisepticum can persist in chickens without development of resistance despite
      several treatments with enrofloxacin.

PMID- 15737484
TI  - Comparison of the indirect haemagglutination and gel diffusion test for
      serotyping Haemophilus parasuis.
AB  - The aim of this study was to compare the use of indirect haemagglutination (IHA)
      and gel diffusion (GD) tests for serotyping Haemophilus parasuis by the Kielstein
      Rapp-Gabrielson (KRG) scheme. All 15 serovar reference strains, 72 Australian
      field isolates, nine Chinese field isolates, and seven isolates from seven
      experimentally infected pigs were evaluated with both tests. With the IHA test,
      14 of the 15 reference strains were correctly serotyped-with serovar 10 failing
      to give a titre with serovar 10 antiserum. In the GD test, 13 reference strains
      were correctly serotyped-with antigen from serovars 7 and 8 failing to react with
      any antiserum. The IHA methodology serotyped a total of 45 of 81 field isolates
      while the GD methodology serotyped a total of 48 isolates. For 29 isolates, the
      GD and IHA methods gave discordant results. It was concluded that the IHA is a
      good additional test for the serotyping of H. parasuis by the KRG scheme if the
      GD methodology fails to provide a result or shows unusual cross-reactions.

PMID- 15737485
TI  - Discrepancies in genetic typing of bovine viral diarrhoea virus isolates.

PMID- 15737486
TI  - Molecular approaches to the identification of biomarkers of exposure and effect-
      report of an expert meeting organized by COST Action B15. November 28, 2003.
AB  - In the past, the term biomarker has been used with several meanings when used in
      human and environmental toxicology as compared to pharmaceutical development.
      However, with the advent of molecular approaches and their application in the
      field of drug development and toxicology, the concept of biomarkers has to be
      newly defined. In the meeting, the experts found consent in defining the term and
      described the application of biomarkers in toxicology, drug development and
      clinical diagnostics. Molecular approaches to biomarker identification and
      selection lead to a large amount of data. Hence, the statistical analysis is
      challenging and special statistical problems have to be solved in biomarker
      characterization, of particular interest are attempts aiming at class discovery
      and prediction. Reliability and biological relevance are to be demonstrated for
      biomarkers of exposure and effect which is also true for biomarkers of
      susceptibility. It is envisaged that the application of biomarkers will expand
      from current use in pre-clinical toxicology to the risk characterization and risk
      assessment of chemicals and from early clinical phases of drug development to
      later phases and even into daily clinical use in diagnostics and disease
      classification.

PMID- 15737487
TI  - The effect on human eye blink frequency of exposure to limonene oxidation
      products and methacrolein.
AB  - Oxidation products of terpenes (e.g. limonene) contain unidentified irritants,
      which may be responsible for a fraction of the reported eye and airway complaints
      in indoor environments. Here we report exposure to parts per billion (ppb) levels
      of limonene oxidation products (LOPs) and the terpene oxidation product
      methacrolein using blink frequency (BF) as a measure of trigeminal stimulation of
      the human eye. Ten male subjects averaging 43 (standard deviation 10.5) years
      were exposed for 20 min to LOPs, methacrolein, and clean air, respectively. A
      baseline BF was measured prior to and following each exposure (8 min and 4 min,
      respectively). The subjects were exposed locally in the non-dominant eye and
      single blind at 20% relative humidity (RH), while viewing an educational film.
      Blinking was video recorded and evaluated for full sessions of 36 min. Mean BF
      increased significantly during exposure to LOPs and methacrolein compared to the
      baseline of clean air, and the findings coincided with weak eye irritation
      symptoms. Lowest observed effect levels were 286 ppb methacrolein and a 10-min
      old LOPs mixture of initially 92 ppb limonene and 101 ppb ozone (O3), which
      increased the BF comparably by 18% (p=0.001) and 17% (p=0.003), respectively. The
      increase in BF was smaller, although not significantly different, during exposure
      to LOPs at 50% RH to 20% RH in mixtures prepared from ca. 350 ppb limonene and
      300 ppb O3. LOPs may cause trigeminal stimulation and possibly eye irritation at
      O3 and limonene concentrations, which are close to high-end values measured in
      indoor settings. The effects may be exacerbated by low RH.

PMID- 15737488
TI  - Close proximity, but not VLA-4-dependent adherence between pre-B cells and bone
      marrow stromal cells, is required for DMBA-induced apoptosis of pre-B cells in
      vitro.
AB  - We have previously reported that 7,12-dimethylbenz[a]anthracene (DMBA) induced
      apoptosis in precursor B lymphocytes (pre-B cells) only when they were co
      cultured with bone marrow stromal (BMS) cells. The goal of this research was to
      determine whether this process was dependent on the adherence of the pre-B cells
      and stromal cells. Conditioned media from DMBA-treated BMS cells induced
      apoptosis in pre-B cells, but only when the pre-B cells were co-cultured with
      stromal cells. This result suggested that stromal cells may release a soluble
      factor that initiates apoptosis, but their presence was still required for
      apoptosis. When the stromal cells and pre-B cells were separated with a membrane
      filter insert, DMBA-induced apoptosis of the pre-B cells was blocked suggesting
      that contact with or close proximity to stromal cells was required for apoptosis.
      The addition of an anti-VLA-4 Mab disrupted adherence of pre-B cells to the
      stromal cell monolayer, but did not diminish the numbers of apoptotic pre-B
      cells. The results of this study support the hypothesis stromal cells and pre-B
      cells must be in close proximity for apoptosis to occur, but direct interaction
      via VLA-4 and VCAM-1 is unlikely to be required for this response.

PMID- 15737489
TI  - Examination of the in vitro (anti)estrogenic, (anti)androgenic and (anti)dioxin
      like activities of tetralin, indane and isochroman derivatives using receptor
      specific bioassays.
AB  - Molecules derived from tetralin, indane and isochroman are often used in the
      synthesis of fragrance materials. The two polycyclic musk fragrances AHTN (6
      acetyl-1,1,2,4,4,7-hexamethyltetralin), HHCB (1,2,4,6,7,8-hexahydro-4,6,6,7,8,8
      hexamethylcyclopenta-gamma-2-benzopyran) and ADBI (4-acetyl-1,1-dimethyl-6-tert
      butylindane) are derived from tetralin, isochroman and indane, respectively. In
      previous studies, AHTN and HHCB have been shown to antagonize estrogen receptors
      (ERs), both in vitro and in vivo. Here, we used two newly developed reporter gene
      assays, to examine the agonistic and antagonistic properties of several indane,
      tetralin and isochroman derivatives towards the human androgen receptor (AR) and
      aryl hydrocarbon receptor (AhR). Additionally, we also assessed
      (anti)estrogenicity of these compounds. A number of compounds showed weak
      estrogenic activity towards the human ER alpha. Several compounds showed
      (anti)estrogenic effects, starting at a concentration of 0.1 microM.
      Surprisingly, almost all compounds were found to be AR antagonists, starting at
      0.1 microM. None of the compounds tested, showed either agonism or antagonism
      towards the AhR. Non-specific effects via crosstalk of the AhR and the ER or AR
      can therefore be ruled out. As far as we are aware, molecules derived from
      indane, tetralin and isochroman showing direct interaction with the ER and AR
      have not been reported previously.

PMID- 15737490
TI  - Influence of hOGG1, XRCC1 and XRCC3 genotypes on biomarkers of genotoxicity in
      workers exposed to cobalt or hard metal dusts.
AB  - Identification of genetic polymorphisms responsible for reduced DNA repair
      capacity may allow better cancer prevention. We examined whether variations in
      genes involved in base-excision (hOGG1, XRCC1) and double strand break (XRCC3)
      DNA repair contribute to inter-individual differences in genotoxic effects
      induced in the lymphocytes of 21 cobalt (Co) exposed, 26 hard metal (WC-Co)
      exposed and 26 matched control male workers. Genotyping was performed by PCR
      RFLP. DNA single strand breaks and alkali-labile sites were measured by the
      alkaline Comet assay. Chromosomal rearrangements resulting from chromosome loss
      or acentric fragments were assessed as micronucleated mononucleates (MNMC) and
      binucleates (MNCB) with the cytokinesis-block micronucleus test. Urinary 8
      hydroxydeoxyguanosine (8-OHdG) levels were used as an indicator of systemic
      oxidative DNA damage. A significantly higher frequency of MNMC was observed in WC
      Co exposed workers with variant hOGG1(326) genotype. Multivariate analysis
      performed with genotypes, age, exposure status, type of plant, smoking and their
      interaction terms as independent variables indicated that MNMC and Comet tail DNA
      (TD) were influenced by genetic polymorphisms. In the exposed and total
      populations, workers variant for both XRCC3 and hOGG1 had elevated MNMC
      frequencies. Further studies will demonstrate whether genotyping for hOGG1 and
      XRCC3 polymorphisms is useful for a better individual monitoring of workers.

PMID- 15737491
TI  - Effects of in utero and lactational exposure to tamoxifen in SD rats.
AB  - Pregnant CD (SD) IGS rats were given tamoxifen (TMX) orally at doses of 0.12,
      0.6, or 3 microg/kg/day from gestational day 6 to postnatal day 21, and the
      effects of TMX exposure on all offspring were examined 10 weeks after birth; the
      reproductive performance of the offspring was also evaluated. Although the body
      weights of the dams treated with TMX remained normal from gestational day 6 until
      the day of autopsy (postnatal day 21), three dams in the 3 microg/kg/day group
      died during the pregnancy or partum periods. These deaths were regarded as the
      toxicological effects of TMX. No changes were detected in the reproductive
      parameters of all the TMX groups except for a decrease in the number of
      newborns/live newborns in the 3 microg/kg/day group. No abnormal clinical signs,
      body weight change, ano-genital distance, vaginal opening, or organ weight
      changes were detected in any of TMX groups, but the day of preputial separation
      was prolonged in the male offspring of all TMX groups and cleft phallus was
      detected in the female offspring of the 0.6 and 3 microg/kg/day groups. No
      abnormalities were detected in the reproductive performance of the male and
      female offspring.

PMID- 15737492
TI  - Ascorbic acid and alpha-tocopherol as potent modulators of apoptosis on arsenic
      induced toxicity in rats.
AB  - Apoptosis or programmed cell death (PCD) is a genetically regulated cellular,
      physiological and biochemical suicidal mechanism that plays a crucial role in the
      development and defense of homeostasis, in which the cell participates in its own
      demise via a cascade of molecular interactions. PCD can be modulated by various
      stimuli including infectious agents or drugs. Arsenic is one among inducible
      toxic agent that triggers apoptosis via free radical generation. Since the
      generation of free radicals during the metabolism of arsenic is thought to be
      involved in arsenic toxicosis, understanding the deleterious effects caused by
      the ROS that attack the vital molecules like DNA has become important. The
      present work was conducted to evaluate the regulatory effect exerted by Vitamin C
      and Vitamin E upon the apoptotic process, which can be assessed by the presence
      of cells with apoptosis associated DNA breaks and characterize the role of TNF
      alpha and caspase-3 in rats intoxicated with arsenic. Male albino rats of wistar
      strain (120-150 g) were used in this study and are further divided into seven
      groups. We observed that ascorbate and alpha-tocopherol selectively altered the
      extent of DNA damage by reducing TNF-alpha level and inhibiting the activation of
      caspase cascade, from these observations it is strongly believed that the present
      vitamins supplementation perspective, though observed in animal model, will have
      sustainable curative value among the already afflicted populations, neutralizing
      impact on freshly emerging arsenicosis scenario and possible proactive protection
      to those potentially susceptible to arsenicals exposure.

PMID- 15737493
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced impairment of glucose-stimulated
      insulin secretion in isolated rat pancreatic islets.
AB  - We have explored the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      administration on the secretory function of isolated rat pancreatic islets.
      Twenty-four hours after TCDD administration (1 microg/kg b.w., i.p.), rats showed
      no significant differences in plasma glucose, insulin, triglycerides and leptin
      levels whereas plasma-free fatty acids were significantly increased with respect
      to untreated controls. In isolated islets, DNA and protein content were
      unchanged, whereas insulin content was significantly decreased in TCDD-treated
      rats. Incubation with different concentrations of glucose demonstrated a
      significant impairment of glucose-stimulated insulin secretion in islets isolated
      from TCDD-treated rats, whereas insulin release was better preserved upon alpha
      ketoisocaproate stimulation. A significant reduction of [3H]-2-deoxy-glucose
      uptake was observed in pancreatic tissue of TCDD-treated rats, whereas no
      significant reduction in GLUT-2 protein levels was detectable by immunoblotting
      in islets from TCDD-treated rats. We concluded that low-dose TCDD could rapidly
      induce significant alterations of the pancreatic endocrine function in the rat.

PMID- 15737497
TI  - [Perioperative acute renal failure].

PMID- 15737494
TI  - Re: Comments on paper by Son et al.

PMID- 15737498
TI  - [Postoperative acute renal failure: definition, diagnostic and prognostic
      criteria].

PMID- 15737499
TI  - [Acute renal failure: epidemiology, incidence and prognostic criteria].

PMID- 15737500
TI  - [On what mechanism of renal aggression is it possible to intervene?].

PMID- 15737501
TI  - [On which renal haemodynamic and renal function parameters can we act to protect
      the kidney?].

PMID- 15737502
TI  - [Which are the risk factors related to the patients status likely to promote
      perioperative acute renal insufficiency?].

PMID- 15737503
TI  - [Which are the factors of toxic and pharmacological risk implicated in occurrence
      of acute renal failure during the perioperative period?].

PMID- 15737505
TI  - [What information is provided by transplantation on renal protection?].

PMID- 15737504
TI  - [Which are the characteristics of the surgical situations at risk of acute renal
      failure?].

PMID- 15737506
TI  - [Which benefit for patient can we expect from hyperhydration and haemodynamic per
      and postoperative optimization? (I)].

PMID- 15737507
TI  - [Which benefit for patient can we expect from hyperhydration and haemodynamic per
      and postoperative optimization? (II)].

PMID- 15737508
TI  - [Which are the therapeutic interventions allowing to ensure a protection of the
      renal function?].

PMID- 15737509
TI  - [Can the strategies of management of acute renal failure modify its prognostic
      and evolution?].

PMID- 15737510
TI  - Tigecycline: clinical evidence and formulary positioning.
AB  - Tigecycline, is a novel broad-spectrum glycylcycline antibiotic, which has
      activity against a broad range of Gram-positive, Gram-negative, atypical,
      anaerobic and antibiotic-resistant bacteria. This includes activity against MRSA,
      VRE and penicillin resistant Streptococcus pneumoniae. Whilst exhibiting
      antibacterial activities typical of earlier tetracyclines, it has more potent
      activity against tetracycline-resistant organisms. Although a bacteriostatic
      compound in vitro, its effectiveness in clinical trials suggests that traditional
      laboratory thinking about using bacteriostatic drugs in serious infections needs
      to be revised. Unlike existing tetracyclines, tigecycline is only available as an
      intravenous preparation, is administered twice daily although its long half life
      and post-antibiotic effect may make once daily dosing possible, appears to have
      good tissue penetration (e.g. skin) and requires no adjustment in the presence of
      renal or hepatic diseases. It is efficacious in complicated skin and soft tissue
      infections and in intra-abdominal infections. In three trials, it was well
      tolerated despite increased frequency of nausea and vomiting. In the light of
      these early clinical data and the likelihood that this agent will become
      available for clinical use within the next 12-24 months, this review aims to
      summarise the key clinical data and potential formulary considerations for the
      future use of this agent, subject to further clinical trials and publication of
      clinical human data.

PMID- 15737511
TI  - Antimicrobial use and Pseudomonas aeruginosa susceptibility profile in a cystic
      fibrosis centre.
AB  - The susceptibility patterns of 1315 mucoid and non-mucoid Pseudomonas aeruginosa
      strains from 224 patients were determined along with antibiotic utilisation in a
      Cystic Fibrosis Centre from 1993 to 1997. Ceftazidime was the most active agent
      (86.0% sensitive isolates), followed by piperacillin-tazobactam (81.7%),
      aztreonam (80.3%), imipenem (80%), piperacillin (76.8%), tobramycin (76.5%),
      ciprofloxacin (73.7%), ticarcillin (72.4%), ticarcillin-clavulanic acid (70.2%),
      amikacin (69.5%), netilmicin (56.5%), meropenem (79%) and imipenem (75.5%). The
      most frequently used compounds were nebulized colistin (mean+/-S.D., 109+/-45
      defined daily doses per 1000 patients per day), followed by ciprofloxacin (98+/
      8), tobramycin (55+/-9), ceftazidime (31+/-8) and amikacin (55+/-9). The mean
      antibiotic consumption by our CF patients was 413+/-47 defined daily doses per
      1000 patients per day. Trend testing showed a significant decline of
      susceptibility to aminoglycosides, imipenem and ciprofloxacin, while the
      susceptibility of P. aeruginosa to piperacillin and ceftazidime was stable.

PMID- 15737512
TI  - Susceptibility testing of urinary isolates of Escherichia coli to mecillinam
      using NCCLS methodology.
AB  - Criteria for susceptibility testing of mecillinam against 533 isolates of
      Escherichia coli and a further 309 Enterobacteriaceae, according to NCCLS
      methodology, were determined. Correlation of MIC to inhibition zones was good for
      all species. For urinary isolates of E. coli, the following agar dilution
      breakpoints and corresponding interpretive zone diameters seem appropriate: < or
      = 8 mg/L/> or = 15 mm for susceptible; 16 mg/L/12-14 mm for intermediate
      susceptible and > or = 32 mg/L/< or = 11 mm for resistant. The appearance of
      isolated colonies within the inhibition zone was sometimes noted with disc
      diffusion, particularly for non-E. coli Enterobacteriaceae. The relevance of
      these colonies to clinical (bacteriological) efficacy was determined and the
      results suggested that they could be ignored when testing urinary E. coli.

PMID- 15737513
TI  - Factors affecting the antimicrobial activity of ovine-derived cathelicidins
      against E. coli 0157:H7.
AB  - Antimicrobial peptides extracted from ovine neutrophils have potential to be high
      value by-products of the lamb industry as, for example, a biopreservative for
      chilled lamb products. This work was carried out to determine the conditions in
      which ovine peptides are most effective and to assist in product development. The
      activities of three synthetic ovine-derived antimicrobial peptides tested were
      not significantly affected by pH or temperature. However, they exhibited
      decreased activity at high ionic strengths and in the presence of divalent
      cations. The three peptides worked better in combination than individually.

PMID- 15737514
TI  - Discordant resistance interpretations in multi-treated HIV-1 patients.
AB  - The routine determination of drug resistance has become an important part of the
      clinical management of HIV-1 infected patients. Plasma samples from 130
      individuals treated for at least 1 year with multiple NRTIs and NNRTIs were
      tested for the presence of mutations correlated to drug resistance. Since
      interpretation criteria represent a crucial point for virologists and clinicians,
      often complicated by the presence of novel and/or complex mutations patterns, we
      analyzed results interpreted by TruGene HIV-1 (Visible Genetics, Toronto,
      Ontario, Canada) and VirtualPhenotype (Virco, Mechelen, Belgium). A high degree
      of concordance was found for NNRTIs whereas NRTIs interpretation was highly
      discrepant. Since different approaches to monitoring resistance reflect different
      interpretation of results, the prediction of drugs resistance from a given HIV
      sequence might be contradictory and requires accurate standardization and unique
      interpretative rules.

PMID- 15737515
TI  - Antibiotic-induced apoptosis in human activated peripheral lymphocytes.
AB  - Long-term administration of macrolide antibiotics reduced the number of
      lymphocytes in bronchoalveolar lavage fluid in patients with chronic airway
      inflammatory disease. To evaluate the inflammatory activity of macrolides, their
      effect on apoptosis of activated lymphocytes isolated from human peripheral blood
      was compared with that of other antibiotics. Macrolides, including clarithromycin
      and azithromycin, at a final concentration of 100 microg/ml accelerated apoptosis
      of activated lymphocytes, while other antibiotics such as fosfomycin sodium, beta
      lactams--ceftazidime, piperacillin sodium and biapenem, and a quinolone,
      ofloxacin, did not cause significant induction of apoptosis. Our results suggest
      that 14- or 15-membered ring macrolides are specifically involved in the
      augmentation of apoptosis of activated lymphocytes, and this may be of value
      therapeutically for chronic airway diseases.

PMID- 15737516
TI  - Usefulness of various antibiotics against Mycobacterium avium-intracellulare,
      measured by their mutant prevention concentration.
AB  - This study looked the selection of resistant mutants in Mycobacterium avium
      intracellulare during antibiotic treatment. The mutant prevention concentration
      (MPC) of 20 Mycobacterium avium and 12 Mycobacterium intracellulare isolates was
      determined. Fifty percent of Mycobacterium avium strains had MPC (MPC50) values
      lower than 16, 64, 40, 55 and 60 mg/L for rifabutin, rifampicin, ciprofloxacin,
      levofloxacin and moxifloxacin, respectively. In the case of Mycobacterium
      intracellulare, 50% had MPC (MPC50) values below 60, 30, 35, 16, 2.5 and 14 mg/L
      for linezolid, rifabutin, levofloxacin, gatifloxacin, moxifloxacin and
      clarithromycin, respectively. The high capacity for selecting resistant mutants
      of all the antibiotics studied emphasises the need to restore the immune system
      if necessary and to administer combined treatments in order to cure patients.

PMID- 15737517
TI  - Effectiveness of spiramycin in murine models of acute and chronic toxoplasmosis.
AB  - The antitoxoplasmic activity of spiramycin (SPI) was evaluated in murine models
      of infection using a type-1 (RH) or type-2 (Me49) strain of Toxoplasma gondii. In
      mice infected with 10(2) tachyzoites of the RH strain, treatment with 100 and 200
      mg SPI/kg/day had only a limited effect; despite some dose-dependent prolongation
      of survival, it was unable to protect mice against death. In contrast, in acute
      infection induced by peroral inoculation of 10, but not 20, cysts of the Me49
      strain, a 3-week course of 100 mg SPI/kg/day and a 4-week course of 200 mg/kg/day
      significantly enhanced protection and markedly reduced brain cyst burdens at 6
      months post infection (p.i.). In chronic infection established by inoculation of
      10 cysts 3 months previously, a 3-week course of 200 mg SPI/kg/day resulted in
      significantly decreased brain cyst burdens compared with controls, both 2 weeks
      after treatment cessation and by 6 months p.i. Although a favourable effect on
      chronic infection may be specific for mice, these data merit investigation, since
      they may have clinical ramifications.

PMID- 15737518
TI  - Impact of inadequate surgical antibiotic prophylaxis on perioperative outcome and
      length of stay on ICU in general and trauma surgery. Analysis using automated
      data collection.
AB  - Within surgical departments, a large amount of antibiotics is used for
      perioperative prophylaxis. Despite the existence of several guidelines and
      recommendations for administering antibiotic prophylaxis, mistakes still do occur
      and have an unknown impact on outcome severity. Based on the electronic
      anaesthesia records of 4304 patients undergoing defined surgical procedures
      requiring perioperative antibiotic prophylaxis, a matched pairs approach was used
      to evaluate the impact of inadequate antibiotic prophylaxis on hospital mortality
      and prolonged length of stay on intensive care. Stepwise regression models were
      developed to predict the impact of inadequate antibiotic prophylaxis on outcome
      measures. An inadequate antibiotic prophylaxis was found for a total of 877
      cases. 77.9% of cases were successfully matched, leading to 683 cases and
      controls each. The crude mortality ratio of cases to controls was 1.5 (cases = 21
      versus controls = 14; P = 0.19). The case group had a significantly (P < 0.01)
      prolonged stay on ICU when analysed as a metric variable. Using logistic
      regression analysis, we could determine that inadequate antibiotic prophylaxis
      had no impact on either hospital mortality or prolonged length of stay on ICU (>1
      day; yes or no).

PMID- 15737519
TI  - Bacteriological efficacy of 5-day therapy with telithromycin in acute maxillary
      sinusitis.
AB  - Increasing resistance among the key pathogens responsible for community-acquired
      respiratory tract infections, namely Streptococcus pneumoniae, Haemophilus
      influenzae and Moraxella catarrhalis, has the potential to limit the
      effectiveness of the antibacterial agents available to treat these infections.
      Moreover, there are regional differences in the susceptibility patterns observed
      and, as treatment is usually empirical, choosing an effective treatment can be
      challenging. Telithromycin, the first ketolide to be approved for clinical use,
      offers an activity profile that covers the key respiratory pathogens including
      penicillin- and macrolide-resistant S. pneumoniae as well as beta-lactamase
      producing H. influenzae and M. catarrhalis. In a pooled analysis of three large
      controlled clinical trials involving patients with acute maxillary sinusitis, the
      bacteriological efficacy of 5- or 10-day treatment with telithromycin and 10-day
      treatment with comparators was evaluated. Telithromycin administered as a once
      daily 800 mg dose for 5 days achieved eradication rates of 91.8, 87.5 and 92.9%
      for S. pneumoniae, H. influenzae and M. catarrhalis, respectively.
      Bacteriological eradication of 8/10 and 12/14 isolates of S. pneumoniae resistant
      to penicillin and erythromycin, respectively, was also reported following 5-day
      treatment with telithromycin. The clinical efficacy of this regimen was
      equivalent to that of a 10-day regimen of telithromycin or standard 10-day
      courses of amoxicillin-clavulanic acid or cefuroxime axetil. Telithromycin 800mg
      given for 5 days was well tolerated, with the majority of adverse events being of
      mild or moderate intensity. These data suggest that telithromycin provides
      effective first-line therapy for use in patients with acute maxillary sinusitis
      in a short and convenient once-daily dosage regimen.

PMID- 15737520
TI  - Cranberry high molecular weight constituents promote Streptococcus sobrinus
      desorption from artificial biofilm.
AB  - Dental biofilm harbouring oral bacteria is highly correlated with the progression
      of dental diseases. Disruption of biofilm formation via anti-adhesion agents is
      an alternative means to the antibacterial approach. Previous studies have shown
      that high molecular weight non-dialysable material (NDM) derived from cranberry
      juice inhibits the adhesion of Escherichia coli and the coaggregation of a
      variety of oral bacteria. In addition, it inhibits the formation of glucans and
      fructans synthesised by GTF and FTF. In the present study, we examined the anti
      adhesion effect of NDM on S. sobrinus. NDM promoted desorption of S. sobrinus
      from biofilm in the presence and absence of extracellular glucans and fructans,
      although the effect was more pronounced in the absence of these polysaccharides.
      Precoating of the bacteria with NDM reduced their ability to form biofilm. Our
      results indicate that NDM could be exploited as an anti-biofilm agent.

PMID- 15737521
TI  - Immunomodulation by non-absorbable antibiotics given by the intragastric route.
AB  - To test the role of bacterial fractions released from intestinal flora during
      immunomodulation by antimicrobial agents, BALB/c mice were treated with the non
      absorbable antibiotics polymyxin B or teicoplanin by the intragastric route. The
      composition of faecal microbiota and the capacity of spleen cells to proliferate
      in response to B-cell and T-cell mitogens were assessed at several times during
      the treatment. Both antibiotics lowered the count of some bacteria of the
      intestinal flora and induced significant modifications in spleen cell ability to
      proliferate in response to mitogens. Thus, the active fractions released from
      intestinal bacteria during antibiotic treatments may be able to induce
      immunomodulating effects.

PMID- 15737522
TI  - Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients.
AB  - It is well known that ceftriaxone leads to pseudolithiasis in some patients.
      Clinical and experimental studies also suggest that situations causing
      gallbladder dysfunction, such as fasting, may have a role for the development of
      pseudolithiasis. In this study, we prospectively evaluated the incidence and
      clinical importance of pseudolithiasis in paediatric surgical patients receiving
      ceftriaxone treatment, who often had to fast in the post-operative period. Fifty
      children who were given ceftriaxone were evaluated by serial abdominal sonograms.
      Of those, 13 (26%) developed biliary pathology. Comparison of the patients with
      or without pseudolithiasis revealed no significant difference with respect to
      age, sex, duration of the treatment and starvation variables. After cessation of
      the treatment, pseudolithiasis resolved spontaneously within a short period. The
      incidence of pseudolithiasis is not affected by fasting.

PMID- 15737523
TI  - Phenotypic and genotypic characterization of macrolide resistant Streptococcus
      pneumoniae recovered from adult patients with community-acquired pneumonia in an
      Argentinian teaching hospital.
AB  - Streptococcus pneumoniae isolates (n = 262) were recovered from adult patients
      with community-acquired pneumonia. Erythromycin-resistance levels increased from
      9% (1997-1998) to 16% (2000-2002). Sampling for resistance mechanisms prevalent
      within 19 erythromycin-resistant S. pneumoniae showed mef(E) in 13/19 isolates
      while 4/19 carried the erm(B) gene (3/19 cMLS(B) and 1/19 iMLS(B) phenotype). MIC
      ranges for erythromycin and clindamycin were 0.5-16 mg/l and <0.008-0.063 mg/l
      for the M phenotype, 128-512 mg/l and 128-256 mg/l for the cMLS(B) phenotype, and
      4 and <0.008 mg/l for the iMLS(B) phenotype. This is the first report studying
      the prevalence of macrolide resistance determinants in S. pneumoniae in our
      country.

PMID- 15737524
TI  - Potential fungicidal effect of voriconazole against Candida spp.
AB  - In vitro fungistatic and fungicidal activities of voriconazole were evaluated
      against 114 isolates of Candida spp. MICs were determined using the NCCLS M27-A2
      broth microdilution method. Minimum fungicidal concentrations (MFCs) were defined
      as the lowest drug concentrations that yielded < or = 5 colonies (> or = 98%
      killing activity). The fungicidal activity could be only evaluated against 45.6%
      of the isolates (52 of 114 isolates) because trailing growth occurred, and 30 of
      these 52 isolates (57.69%) showed MFC values < or = 1 mg/l. There was little or
      no fungicidal activity against C. albicans and C. tropicalis. In contrast, all C.
      krusei were killed by 1-2 mg/l voriconazole. In conclusion, our data show that
      the fungicidal effect of voriconazole against Candida spp. is species dependent.

PMID- 15737525
TI  - Mobiluncus species in gynaecological and obstetric infections: antimicrobial
      resistance and prevalence in a Turkish population.
AB  - The purpose of this study was to determine the prevalence and antimicrobial
      resistance of Mobiluncus species isolated from specimens collected from Turkish
      women with gynaecological infections. Mobiluncus species were isolated on
      enriched Schaedler agar and RLK agar plates under anaerobic conditions. The MICs
      of various antibiotics were evaluated using an agar dilution procedure. The
      prevalence of Mobiluncus species isolated from vulvo-vaginal abscesses,
      endometrial smears, salpingitis and bacterial vaginosis was 2%, 4.7%, 3.8% and
      49%, respectively. Mobiluncus isolates were only resistant to metronidazole (81%
      resistance). The isolation rate of M. curtisii was higher than M. mulieris in
      Turkish women with bacterial vaginosis, vulvo-vaginal abscesses, endometritis or
      salpingitis.

PMID- 15737526
TI  - Occurrence of multi-resistant Salmonella enterica Typhimurium DT 104 in Austria
      isolated from humans, animals and food.

PMID- 15737527
TI  - Caspofungin as treatment for Candida glabrata hip infection.

PMID- 15737528
TI  - Reproducibility of daptomycin MIC results using dry-form commercial trays with
      appropriate supplemental calcium content.

PMID- 15737529
TI  - Methicillin-resistant Staphylococcus aureus in Bangladesh--a multicentre study.

PMID- 15737530
TI  - Impacts of PEG-6000 pretreatment for barley (Hordeum vulgare L.) seeds on the
      effect of their mature embryo in vitro culture and primary investigation on its
      physiological mechanism.
AB  - In this paper, we studied polyetheneglycol (PEG) pretreatment effect on the
      mature embryo culture in vitro by using barley (Hordeum vulgare L.) seeds.
      Meanwhile, we analyzed and assayed its mineral element and endogenous hormone
      level. The experimental results were as follows: (1) PEG-6000 imbibition could
      obviously slow down the water timecourse absorbed by barley seeds; (2) 10% PEG
      6000 treatment of barley seeds for 3 h had a positive effect on germination in
      vitro and callus induction of the barley seed mature embryos; (3) 10% PEG-6000
      treatment inhibited soluble leakage from the seeds; (4) N leakage was mainly from
      the endosperms, Mn2+ leakage from embryos; (5) PEG-6000 treatment changed greatly
      the hormone level (ABA, IAA, GAs), which influenced the percentage of plantlets
      from the mature embryo callus. The results can provide some clues to scientific
      sowing of crop seeds, pretreatment for the purpose of uniform seedlings, and the
      explant response quality in plant tissue culture.

PMID- 15737531
TI  - The synergistic activity of antibiotics combined with eight traditional Chinese
      medicines against two different strains of Staphylococcus aureus.
AB  - The ethanolic extracts of eight traditional Chinese medicines and four
      antibiotics were investigated for their combined effects on the resistance of
      Staphylococcus aureus (S. aureus) in vitro. Methicillin resistant S. aureus,
      which was isolated from patient and a standard strain, were used. Our results
      showed that there are differences in the effects of many combinations used on the
      standard strain and resistant strain of S. aureus. The ethanolic extracts of
      Isatis tinctoria, Scutellaria baicalensis and Rheum palmatum can improve the
      antimicrobial activity of four antibiotics we used.

PMID- 15737532
TI  - Incorporating zosteric acid into silicone coatings to achieve its slow release
      while reducing fresh water bacterial attachment.
AB  - Biofouling has posed serious problems in maritime industry including increased
      fuel consumptions, economic loss from ship-hull maintenances, contamination of
      drinking water, and serious corrosion for mechanical instruments. Minimizing the
      attachment of bacteria and formation of biofilm could be advantageous in reducing
      the early stages of biofouling. Zosteric acid, a natural product present in
      eelgrass, was found to have ability for preventing the attachment of some
      bacteria and barnacles. In this study, the antifouling ability of zosteric acid
      during the early stages of fouling was evaluated using attachment studies of
      fresh water bacteria. Simultaneously, various methods were sought for
      incorporating zosteric acid into silicone to prolong the release of the compound.
      The main results from this study were that zosteric acid exhibited anti-bacterial
      attachment regardless of whether it dispersed in water or incorporated into a
      coating. In addition, the release rate of zosteric acid from the incorporated
      coatings, particularly those where zosteric acid was uniformly dispersed with
      aggregates size of 4 microm or less, was orders of magnitude slower than those of
      previous reports. The release results indicate that the service life of our
      coatings could be far extended even with a small amount of zosteric acid
      incorporated.

PMID- 15737533
TI  - Plant protein-polysaccharide interactions in solutions: application of soft
      particle analysis and light scattering measurements.
AB  - The soft particle analysis theory was applied to plant proteins and
      polysaccharides in solution, to determine the charge density of these polymers
      and the depth of the layer accessible by counterions according to pH conditions.
      In addition to the macromolecule shape characterized by light scattering
      measurements, these properties are also correlated with the optimum coacervation
      condition, so as to establish the prevalent plant protein-polysaccharide
      interactions governing the coacervate formation. Globulin was found to be highly
      charged and spherically shaped. The best coacervation condition was obtained at
      the pH value, which corresponds to the protein conformation with a dense and
      compact accessible layer. On the contrary, for the alpha gliadin, bearing a lower
      charge, a more extended conformation seems to be more favourable. For the plant
      proteins studied, the coacervation seems to be controlled by the structure of the
      counter polyanion used: from our model, it turns out that the rod-like structure
      of arabic gum observed at acidic pH allows the interaction with plant proteins to
      form coacervates, contrary to the highly charged and spherical structure of
      alginate.

PMID- 15737534
TI  - Probing adsorbed fibronectin layer structure by kinetic analysis of monoclonal
      antibody binding.
AB  - Adsorbed protein layers are often away from equilibrium and thus exhibit history
      dependent structures. We use the kinetics of monoclonal antibody binding, as
      measured using optical waveguide lightmode spectroscopy (OWLS), to investigate
      the structure of adsorbed fibronectin (Fn) layers formed under different kinetic
      paths. For all of the layers investigated, we find no difference between the
      apparent adsorption rate constants of (i) monoclonal antibodies specific to Fn's
      cell binding site (alpha-Fn) and (ii) monoclonal antibodies specific to
      cytochrome c (alpha-CC, as a control), indicating initial adsorption of
      antibodies to be non-specific. For certain layers, the saturation density and the
      initial projected area per antibody differ significantly between alpha-Fn and
      alpha-CC, suggesting specific binding to follow the initial non-specific
      attachment. The fraction of antibodies binding specifically to the Fn layer, and
      the number of Fn binding sites per specific binding event, are estimated in terms
      of the difference in initial projected areas between alpha-Fn and alpha-CC. For a
      Fn layer formed at a bulk concentration of 2 microg/mL, we find a decrease in
      specific binding with an increase in Fn layer formation time, suggesting post
      adsorption structural changes of a lower density adsorbed layer diminish binding
      site availability. Conversely, for a Fn layer formed at a bulk concentration of
      40 microg/mL, we find an increase in specific binding with an increase in the
      aging time of the Fn layer, implying post-adsorption structural changes reveal
      binding sites for a higher density adsorbed layer.

PMID- 15737535
TI  - Atomic force microscopy studies of ganglioside GM1alpha in
      dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine mixed monolayers and
      hybrid bilayers.
AB  - The membrane states of the alpha-series ganglioside GM1alpha in 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC) mixed monolayers and hybrid bilayers were investigated using atomic force
      microscopy (AFM). The AFM image for the GM1alpha/DOPC/DPPC ternary monolayers
      showed the formation of GM1alpha-raft in the DOPC matrix. As increase of the
      surface pressure, GM1alpha are condensed in DPPC-rich domains; long and slender
      GM1alpha-rafts are separated from the DPPC-rich domains into the DOPC matrix. The
      GM1alpha/DOPC/DPPC ternary monolayers were deposited on mica coated with the
      first layer (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine: DPPE) using the
      Langmuir-Schaeffer technique. The AFM image for the hybrid bilayers showed that
      same molecules were heterogeneously concentrated according to increase of the
      surface pressure to form GM1alpha-raft, DPPC-rich domain and DOPC matrix, being
      in agreement with the observation on the monolayer experiment. The found
      phenomenon implies that a binding of lectin to GM1alpha causes the increase of
      the surface pressure, the localization of GM1alpha and the succeeding formation
      of the raft as a first step of a specific signal transduction.

PMID- 15737536
TI  - Microencapsulation peptide and protein drugs delivery system.
AB  - Many methods were used to devise peptide and protein drugs delivery system (DDS).
      Because of their relatively large size, they have low transdermal
      bioavailabilities. In systemic delivery of proteins, biodegradable material as
      parenteral depot formulation occupy an important place because of several aspects
      like protection of sensitive proteins from degradation, prolonged or modified
      release, pulsatile release patterns. The main objective in developing controlled
      release protein injectables is avoidance of regular invasive doses which in turn
      provide patient compliance, comfort as well as control over blood levels. This
      review article presents the outstanding contributions in field of
      microencapsulation as protein delivery systems and different approaches of
      protein delivery are described. Then discusses how these advances may be applied
      to resolve the challenges face the development of microcapsule for the
      controllable delivery of protein drugs.

PMID- 15737537
TI  - Electrostatic interactions between model mitochondrial membranes.
AB  - Lipids are very diverse in both their respective structures and functions; and
      cells exquisitely control membrane composition. One intriguing issue is the
      specific role of lipids in modulating the physical properties of membranes.
      Cardiolipin (CL) is a unique four-tailed, doubly negatively charged lipid found
      predominately within the inner mitochondrial membrane, and is thought to be
      influential in determining the inner mitochondrial membrane potential and
      permeability. To determine the role of cardiolipin in modulating the charge
      properties of membranes, this study investigated the electrostatic interactions
      between mixed cardiolipin and phosphatidylcholine bilayers as a function of
      cardiolipin concentration. For physiologically relevant concentrations of
      cardiolipin, the surface charge density of the membrane was found to increase
      linearly with increasing concentration of cardiolipin. However, only a fraction
      of the cardiolipin molecules predicted to carry a charge from pK-values were
      ionized. Clearly environmental factors, beyond that of pH, play a role in
      determining the charge of bilayers containing cardiolipin.

PMID- 15737538
TI  - Retention of microbial cells in substratum surface features of micrometer and sub
      micrometer dimensions.
AB  - Surfaces were produced with defined topographical features and surface chemistry.
      Silicon wafers, and wafers with attached nucleopore filters and quantifoils were
      coated with titanium using ion beam sputtering technology. Irregularly spaced,
      but regularly featured surface pits, sizes 0.2 and 0.5 microm, and regularly
      spaced pits with regular features (1 and 2 microm) diameter were produced. The
      smallest surface feature that could be successfully produced using this system
      was of diameter 0.2 microm. Ra, the average absolute deviation of the roughness
      irregularities from the mean line over one sampling length, Rz, the difference in
      height between the average of the five highest peaks, and the five lowest valleys
      along the assessment length of the profile and surface area values increased with
      surface feature size, with Ra values of 0.04-0.217 microm. There was no
      significant difference between the contact angles observed for smooth titanium
      surfaces with 0.2 and 0.5 microm features. However, a significant difference in
      contact angle was observed between the 1 and 2 microm featured surfaces
      (p<0.005). Substrata were used in microbial retention assays, using a range of
      unrelated, differently sized microorganisms. Staphylococcus aureus (cells 0.5-1
      microm diameter) were retained in the highest numbers. S. aureus was well
      retained in the 0.5 microm sized pits and began to accumulate within larger
      surface features. Rod shaped Pseudomonas aeruginosa (1 microm x 3 microm) were
      preferentially retained, often end on, within the 1 microm surface features. Some
      daughter cells of Candida albicans blastospores were retained in 2 microm pits.
      For S. aureus and P. aeruginosa, the greatest numbers of cells were retained in
      the largest (2 microm) surface features. The number of C. albicans was similar
      across all the surfaces. The use of defined surfaces in microbial retention
      assays may lead to a better understanding of the interaction occurring between
      cells and surface features.

PMID- 15737539
TI  - Interaction between bovine serum albumin and equimolarly mixed cationic-anionic
      surfactants decyltriethylammonium bromide-sodium decyl sulfonate.
AB  - The interactions of bovine serum albumin (BSA) with the anionic surfactant sodium
      decylsulfonate (C10SO3), the cationic surfactant decyltriethylammonium bromide
      (C10NE) and equimolarly mixed cationic-anionic surfactants C10NE-C10SO3 were
      investigated by surface tension, viscosity, dynamic light scattering (DLS) and
      circular dichroism (CD). It was shown that the single ionic surfactant C10SO3 or
      C10NE has obvious interaction with BSA. The presence of C10SO3 or C10NE modified
      BSA structure. However, the equimolarly mixed cationic-anionic surfactants C10NE
      C10SO3 showed very weak interactions with BSA. The surface tension-log
      concentration (gamma-logC) plot for the aqueous solutions of C10NE-C10SO3/BSA
      mixtures coincided with that of C10NE-C10SO3 solutions. Viscometry showed that
      there is no significant change in the rheological properties for the C10NE
      C10SO3/BSA mixed solutions. DLS showed that BSA monomers and mixed aggregates of
      C10NE-C10SO3 existed in the C10NE-C10SO3/BSA mixed solutions. From CD spectra no
      obvious modification of BSA structure in the presence of C10NE-C10SO3 mixtures
      was observed. The weak interactions between BSA and C10NE-C10SO3 might be
      explained in terms of the very low critical micelle concentration (cmc) of C10NE
      C10SO3 mixtures that made the concentration of ionic surfactant monomers much
      lower than that needed for inducing the modification of BSA structure. In other
      words, the very strong synergism between oppositely charged cationic and anionic
      surfactants makes the formation of cationic-anionic surfactant mixed aggregates
      in the bulk solution a more favorable process than binding to proteins.

PMID- 15737540
TI  - Poly(ethylene glycol) (PEG) enhances dynamic surface activity of a bovine lipid
      extract surfactant (BLES).
AB  - Shortage or malfunction of pulmonary surfactant in alveolar space leads to a
      critical condition termed respiratory distress syndrome (RDS). Surfactant
      replacement therapy, the major method to treat RDS, is an expensive treatment. In
      this paper, the effect of poly(ethylene glycol) (PEG) to improve dynamic surface
      activity of a bovine lipid extract surfactant (BLES) was studied by axisymmetric
      drop shape analysis (ADSA) and a captive bubble method. The activity of BLES+PEG
      mixtures was compared to that of a natural surfactant containing surfactant
      proteins A and D. When PEG was added into BLES mixtures, the surface tension
      hysteresis of BLES films was minimized when the films were compressed by more
      than 50%. PEG also helps to quickly restore surfactant films after film collapse.
      Thus, as far as surface tension effects go, the findings suggest that PEG might
      be used as a substitute for surfactant-associated protein SP-A in therapeutic
      surfactant products, and might also be used to reduce the amount of BLES required
      in clinical applications.

PMID- 15737541
TI  - The impact of ultraviolet light on bacterial adhesion to glass and metal oxide
      coated surface.
AB  - Biofouling of glass and quartz surfaces can be reduced when the surface is coated
      with photocatalytically active metal oxides, such as TiO2 (anatase form) or SnO2.
      We measured the attachment of eight strains of bacteria to these two metal oxides
      (TiO2 and SnO2), and to an uncoated glass (control; designated Si-m) before and
      after exposure to UV light at wavelengths of 254 nm (UVC) or 340 nm UV (UVA).
      TiO2-coated surfaces were photocatalytically active at both 254 and 340 nm as
      evidenced by a decrease in the water contact angle of the surface from 59 degrees
      +/-2 to <5 degrees. The water contact angle of the SnO2 surface was reduced only
      at 254 nm, while contact angle of the Si-m glass surface was not altered by light
      of either wavelength. Bacterial adhesion decreased by 10-50% to photocatalyzed
      glass surfaces. In all cases, bacteria exposed to the UV light were completely
      killed due to a combination of exposure to UV light and the photocatalytic
      activity of the glass surfaces. These results show that UV light irradiation of
      TiO2-coated surfaces can be an effective method of reducing bacterial adhesion.

PMID- 15737542
TI  - Formation of a protein monomolecular layer by a combined technique of LB and SA
      methods.
AB  - This paper describes a technique developed for the formation of the self
      assembled protein monomolecular layer. The main idea is a direct transfer of
      protein molecules consisting of a Langmuir-Blodgett (LB) film onto the surface of
      another chemically modified metal substrate and induction of the spontaneous
      formation of a self-assembled monolayer (SAM) by chemisorption without protein
      aggregates. In the present experiments, a cytochrome c (cyt c) SAM on a gold
      substrate was prepared by incubating a EDC/MUA-modified gold substrate overlaid
      with a cyt c LB film in a phosphate buffer solution. Scanning tunneling
      microscopy (STM) image of a cyt c SAM shows that the size of cyt c clusters in
      the most part of the substrate is approximately 5 nm, indicating the cyt c
      monomolecular layer. The rectifying property of a cyt c monolayer was confirmed
      to remain by an asymmetric I-V curve in the applied bias from -1 V to 1 V.

PMID- 15737543
TI  - Ultra high molecular weight polyethylene and polydimethylsiloxane blend as
      acetabular cup material.
AB  - An acetabular cup shock absorber implant is formed from a composite of polymer
      materials. The cup consists of three zones such as the articulating surface of
      the implant is 100% ultra high molecular weight polyethylene (UHMWPE) (zone 1)
      and shock absorber of the cup contains of polydimethylsiloxane (PDMS) (zone 3).
      Zone 2 which is designed for better adhesion between zone 1 and zone 2 consists
      of a blend of UHMWPE and PDMS is a cushion that from one side adheres to zone 1
      and the other side to zone 2. PDMS and UHMWPE have been blended under conditions
      of shear and elevated temperature in order to form uniform, thermoplastic blends.
      When blends compared to pure UHMWPE, the blends show lowered tensile modulus and
      lowered mixing energies. The UHMWPE crystals are increased in quantity or else
      become more regular, even 50% blend shows no rubbery stage. The morphology and
      dynamic mechanical behavior of the blends were studied using scanning electron
      microscopy (SEM) and dynamic mechanic thermal analysis (DMTA). In this study, the
      biocompatibility have evaluated in vitro the interaction of UHMWPE, silicone and
      PDMS/UHMWPE blends with L929 fibroblast cells.

PMID- 15737544
TI  - Cell separation in microcanal coated with electrically charged phospholipid
      polymers.
AB  - To separate the cell population in whole blood using microcanal, the surface was
      covered with a polyion complex (PIC) composed of electrically charged
      phospholipid polymers. The phospholipids polymers were prepared by the
      polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl
      methacrylate with 3-(methacryloyloxypropyl)-trimethyl ammonium iodide as the
      cationic unit or potassium 3-methacryloyloxypropyl sulfonate as the anionic unit.
      The PIC was formed at the solid-liquid interface, that is, first, the cationic
      polymer was coated on the substrate and an aqueous solution containing the
      anionic polymer with different concentrations was applied to the polymer-coated
      substrate. The formation of the PIC was followed using a quartz crystal
      microbalance (QCM), and the PIC surfaces were analyzed by both zeta-potential
      measurement and X-ray photoelectron spectroscopic measurement. The surface
      electrical potential on the PIC was controllable from +40 to -40 mV by increasing
      the amount of the adsorbed anionic polymer. The PIC surface was prepared in
      microcanal. The surface electrical potential was sequentially changed. When the
      whole blood was introduced into the microcanal, the cells adhered on the
      positively charged surface, but could not adhere to the negatively charged
      surface. Even when the cells adhere to the surface, the morphology of cells was
      maintained. This is due to MPC units at the surface, which show a good
      biocompatibility. These results indicated that the change in the surface
      electrical potential will be a useful method to separate the cells from whole
      blood.

PMID- 15737545
TI  - Surfactant encapsulated DNA: structure characterization and interaction with dye
      molecules in organic media.
AB  - The recognition of electrostatically-bound DNA-didodecyldimethylammonium (DNA
      DDDA) complex by three dye molecules, acridine orange (AO), ethidium bromide (EB)
      and 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin tetra(p-toluenesulfonate)
      (TMPyP) in organic media was investigated through 1H NMR, UV-vis, and circular
      dichroism (CD) spectroscopies. When the organic solvent in which DNA-DDDA complex
      dissolves is changed from ethanol to chloroform, the adsorbed AO undergoes a
      reversible transformation from a monomer to a highly aggregated state at the
      interface between DNA and DDDA. EB also adsorbs at the interface between DNA and
      DDDA when EB interacts with the DNA-DDDA complex in organic media, but its
      existing state is independent of the used solvents. The third dye, TMPyP cation
      can intercalate into the G-C region while its anionic p-tosylate counterion
      remains unbound when it mixes with DNA complex in organic media. The complexes of
      DDDA with previously recognized DNA by the three dye molecules (DNA-dye),
      respectively, are also investigated. AO seems having changed its location from
      the grooves of DNA to the interface between DNA and DDDA after DNA-AO complex was
      electrostatically encapsulated with DDDA. The aggregation behavior of AO also
      shows a dependence on the polarity of the organic solvent. EB molecules are
      believed to intercalate into the base pairs of DNA in aqueous solution. The
      intercalation mode is still maintained after the encapsulation for DNA-EB in
      organic solvents, which is different from the situation between DNA-DDDA complex
      and EB. But in both cases, the existing states of EB are independent of the
      polarity of the organic solvents. Finally, TMPyP in the complex of DNA-TMPyP and
      DDDA is also judged to intercalate into the G-C region of DNA while its anionic p
      tosylate counterion remains separated from DNA complex, which is similar to its
      interaction with DNA-DDDA complex in organic media. These data also strongly
      suggest that the intercalation state of TMPyP is more stable than its adsorption
      state in grooves when it is recognized with DNA. The present results are
      significant for the designs of both laser dye and conductive materials.

PMID- 15737546
TI  - Cytotoxicity characterization of catanionic vesicles in RAW 264.7 murine
      macrophage-like cells.
AB  - In comparison with cationic liposomes, catanionic vesicles possess more
      attractive properties such as stability and lower cost, and these characteristics
      may make them suitable as a non-viral vehicle and for other biomedical
      applications such as vaccine adjuvants. However, very little is known about their
      possible cytotoxic mechanisms in cellular system. Also, this information is vital
      for the future development of safe biomedical systems. In the current study, the
      cytotoxic effect of catanionic vesicles, consisting of anionic surfactant (SDS),
      cationic surfactant (HTMAB), and cholesterol, in cultured RAW 264.7 murine
      macrophage-like cells was determined. The treatment of catanionic vesicles
      produced a dose-dependent effect on macrophage cells. RAW 264.7 cells exposed to
      catanionic vesicles exhibited morphological features of apoptosis such as
      chromatin condensation. Typical apoptotic ladders were observed in DNA extracted
      from RAW 264.7 cells treated by catanionic vesicles. Analysis from flow cytometry
      demonstrated an increase of hypodiploid DNA population (sub-G1) and a
      simultaneous decrease of diploid DNA content, indicating that DNA cleavage
      occurred after exposure of the cells with catanionic vesicles. In addition, it
      was shown that pretreatment of RAW 264.7 cells with the general caspase inhibitor
      (zVAD-fmk) did not prevent apoptosis induced by catanionic vesicles, suggesting
      that apoptosis in macrophage cells followed a caspase-independent pathway induced
      by catanionic vesicles. These data provide novel insight into the effect of
      catanionic vesicles on the mechanisms of cell death induced by catanionic
      vesicles.

PMID- 15737547
TI  - Influence of ultrasonic field on microcystins produced by bloom-forming algae.
AB  - Under the background of algae removal and growth inhibition by ultrasonic
      irradiation, the effects of ultrasonic irradiation on removal of Microcystis, the
      concentration variation of microcystins (MC) produced by Microcystis in
      Microcystis suspension, and sonochemical degradation of microcystins in water,
      were studied in the paper. The results showed that ultrasonic irradiation could
      efficiently inhibit the growth of Microcystis, and ultrasonic irradiation shorter
      than 5 min would not introduce the increase of microcystins dissolved in
      Microcystis suspension simultaneity. Also, microcystins dissolved in Microcystis
      suspension would not increase as ultrasonic power increasing. Further research
      showed that microcystins were effectively degraded in ultrasonic fields. After 20
      min ultrasonic irradiation at 150 kHz and 30 W, the removal rate of microcystins
      reached 70%.

PMID- 15737548
TI  - Agglutination study of poly(allyl-alpha-D-glucopyranose/styrene) latex particles
      in the presence of Concanavalin A.
AB  - Latex agglutination of the glucose-modified latex, which were synthesized by
      emulsion copolymerization of allyl-modified glucose and styrene monomers by
      specific binding interactions between Concanavalin A (Con A) and allyl-alpha-d
      glucopyranose, were investigated. The surface of the glucose-modified latex was
      characterized by dye-partition method and the number of glucose was 1517 per
      latex particle. The average particle size and the polydispersity index of the
      latex were 78.3 and 1.005, respectively. Time-evolution adsorption behavior of
      various concentrations of the Con A and the consequent latex agglutination were
      studied by UV spectrophotometer at 540 nm and zeta-potential analyzer at the
      fixed latex concentration of 0.02 wt%. Specific binding between Con A and allyl
      alpha-D-glucopyranose leaded the latex particles to coagulate by decreasing the
      electrostatic repulsion between the particles and mobility.

PMID- 15737549
TI  - Conformational study of papain in the presence of sodium dodecyl sulfate in
      aqueous medium.
AB  - The interactions between a globular protein, papain and the anionic surfactant,
      sodium dodecyl sulfate (SDS) have been investigated in aqueous medium using
      fluorimetric, circular dichroism, Fourier transform infra-red, UV-vis
      spectrophotometric, dynamic light scattering, and nuclear magnetic resonance
      techniques. The conformational change of papain in aqueous solution has been
      studied in the presence of SDS. The results show the high alpha-helical content
      and unfolded structure of papain in the presence of SDS due to strong
      electrostatic repulsion leading to a "necklace and bead model" in protein
      surfactant complexes.

PMID- 15737550
TI  - Low impact factor of Italian journals: another aspect of the poor research
      funding?

PMID- 15737551
TI  - Debunking dogma and developing theses.

PMID- 15737552
TI  - New science-based endpoints to accelerate oncology drug development.
AB  - Although several new oncology drugs have reached the market, more than 80% of
      drugs for all indications entering clinical development do not get marketing
      approval, with many failing late in development often in Phase III trials,
      because of unexpected safety issues or difficulty determining efficacy, including
      confounded outcomes. These factors contribute to the high costs of oncology drug
      development and clearly show the need for faster, more cost-effective strategies
      for evaluating oncology drugs and better definition of patients who will benefit
      from treatment. Remarkable advances in the understanding of neoplastic
      progression at the cellular and molecular levels have spurred the discovery of
      molecularly targeted drugs. This progress along with advances in imaging and
      bioassay technologies are the basis for describing and evaluating new biomarker
      endpoints as well as for defining other biomarkers for identifying patient
      populations, potential toxicity, and providing evidence of drug effect and
      efficacy. Definitions and classifications of these biomarkers for use in oncology
      drug development are presented in this paper. Science-based and practical
      criteria for validating biomarkers have been developed including considerations
      of mechanistic plausibility, available methods and technology, and clinical
      feasibility. New promising tools for measuring biomarkers have also been
      developed and are based on genomics and proteomics, direct visualisation by
      microscopy (e.g., confocal microscopy and computer-assisted image analysis of
      cellular features), nanotechnologies, and direct and remote imaging (e.g.,
      fluorescence endoscopy and anatomical, functional and molecular imaging
      techniques). The identification and evaluation of potential surrogate endpoints
      and other biomarkers require access to and analysis of large amounts of data, new
      technologies and extensive research resources. Further, there is a requirement
      for a convergence of research, regulatory and drug developer thinking - an effort
      that will not be accomplished by individual scientists or research institutions.
      Research collaborations are needed to foster development of these new endpoints
      and other biomarkers and, in the United States (US), include ongoing efforts
      among the Food and Drug Administration (FDA), National Cancer Institute (NCI),
      academia, and industry.

PMID- 15737553
TI  - Shifting paradigms in prostate cancer; docetaxel plus low-dose prednisone -
      finally an effective chemotherapy.
AB  - Until now, the use of systemic chemotherapy for advanced androgen-independent
      prostate cancer has had very little to offer to patients. However, in 2004, two
      large randomised trials investigating docetaxel vs. mitoxantrone have both
      demonstrated survival improvements, and, in one of the trails, improvements in
      important secondary clinical outcome measures such as pain relief and quality of
      life measurements. In this current perspective, these two trials are summarised
      and discussed. It is concluded that, docetaxel every 3 weeks plus low-dose
      prednisone can be considered standard treatment for patients with androgen
      independent disease.

PMID- 15737554
TI  - Does surgery unfavourably perturb the "natural history" of early breast cancer by
      accelerating the appearance of distant metastases?
AB  - This historical perspective on breast cancer tells us how and why certain
      therapeutic eras have reached ascendancy and then declined. Therapeutic
      revolutions occur after a crisis develops when there is a general recognition
      that clinical interventions are not producing positive results predicted by the
      prevailing paradigm. The attitude of pre-modern surgeons was influenced by the
      very real possibility of doing more harm than good by operating upon women with
      breast cancer. Up until Halsted, the general consensus was clearly that, unless
      forced by the circumstances, surgical resection should be avoided for disease
      much more advanced than very early stage tumours (the cacoethesis of Celsus).
      Twentieth century progress in antisepsis, anaesthesia, and surgery changed this
      point of view. The first three quarters of that century saw more and more
      aggressive operations performed while the last quarter century reversed this
      trend, with reduction of the size of breast cancer operations based largely on
      the teachings of Fisher. A new crisis is upon us now in that trials of early
      detection have resulted in unexpected disadvantages to certain subgroups and
      there is previously unreported structure in early hazard of relapse, clinical
      data that suggests the act of surgery might accelerate the appearance of distant
      metastases. The explanation we propose that agrees with these results, as well as
      physicians of antiquity, is that surgery can induce angiogenesis and
      proliferation of distant dormant micrometastases, especially in young patients
      with positive nodes.

PMID- 15737555
TI  - The potential of statins as part of anti-cancer treatment.
AB  - Statins are known to reduce mortality related to cardiovascular diseases. In
      recent years, evidence has accumulated that statins also exert anti-tumour
      activity for which numerous potential underlying mechanisms of action have been
      suggested. Accordingly, several case-control studies showed a reduction in cancer
      incidence in patients treated with statins. Furthermore, statins interact
      synergistically with several anti-tumour treatments in preclinical studies. Until
      now, only a few clinical studies are available that explore the optimal dose,
      feasibility, and efficacy of statins applied as single agents to control the
      growth of existing tumours. Studies investigating statins as part of a multi-drug
      regimen are completely lacking. Nevertheless, the interesting pre-clinical anti
      tumour activity of statins combined with a favourable toxicity profile warrant
      their further development as anti-tumour agents, in particular as part of multi
      drug regimens.

PMID- 15737557
TI  - Sentinel lymphonodectomy does not increase the risk of loco-regional cutaneous
      metastases of malignant melanomas.
AB  - With regard to malignant melanoma, the impact of lymph node surgery on the
      development of loco-regional cutaneous metastases (LCM) has not yet been
      adequately addressed. However, this aspect is of interest, since sentinel
      lymphonodectomy (SLNE) has been suspected of causing LCM by inducing entrapment
      of melanoma cells. We analysed 244 patients with SLNE and compared the data with
      199 patients treated with delayed lymph node dissection (DLND) for clinically
      palpable metastases. Analysis of both groups commenced at the time of excision of
      the primary tumour, using the Kaplan-Meier method. LCM that appeared as a first
      recurrence, as well as the overall probability of developing LCM, were recorded.
      For sentinel-negative patients with a primary melanoma >1mm thick, the 5-year
      probability of developing LCM as a first recurrence was 6.9 +/- 0.02% (+/
      standard error of the mean (SEM)). The probability was 17.6 +/- 0.03% in the DLND
      group. Comparing the two node-positive subgroups, the probability of developing
      LCM as a first recurrence was significantly higher in patients with positive SLNE
      (27.3 +/- 0.05%, P = 0.03). However, the 5-year overall probability of developing
      LCM did not differ significantly in the node-positive groups (33.3% in the DLND
      group vs. 33.7% in patients with positive sentinel lymph nodes (SLNs)). Since
      early excision of lymphatic metastases by SLNE avoids nodal recurrences, thereby
      prolonging the recurrence-free interval, the chance of LCM to manifest as a first
      recurrence should inevitably increase. However, the overall in-transit
      probability is not increased after SLNE.

PMID- 15737556
TI  - A Phase I trial of prolonged administration of lovastatin in patients with
      recurrent or metastatic squamous cell carcinoma of the head and neck or of the
      cervix.
AB  - Squamous cell carcinomas of the head and neck (HNSCC) and of the cervix (CC) are
      particularly sensitive to the apoptotic effects of lovastatin in vitro. In this
      Phase I study, the safety and maximum related dose (MTD) of lovastatin was
      evaluated in these specific clinical settings. This was a Phase I open-label
      study to determine the recommended Phase II dose (RPTD) of lovastatin in advanced
      HNSCC or CC. This study involved a dose and duration escalation of lovastatin
      starting at 5/mg/kg/day x 2 weeks, every 21 days, until the MTD was reached.
      Plasma samples were collected for pharmacokinetic analysis. All 26 patients
      enrolled were evaluable. Dose-limiting toxicity (DLT) consisting of reversible
      muscle toxicity was seen at 10 mg/kg/day x 14 days. Toxicity may be related to
      relative renal insufficiency. The MTD was determined to be 7.5 mg/kg/day x 21
      days, every 28 days. The low lipid levels experienced on study did not translate
      into adverse events. Biologically relevant plasma lovastatin levels were
      obtained. No objective responses were seen but the median survival of patients on
      study was 7.5 months (mean 9.2 +/- 1.5 months). Stable disease (SD) for more than
      3 months was seen in 23% of patients. One patient achieved SD and clinical
      benefit for 14 months on study and a further 23 months off treatment. The disease
      stabilisation rate of 23% seen in these end-stage patients is encouraging. We
      conclude that the administration of lovastatin at 7.5 mg/kg/day for 21
      consecutive days on a 28-day schedule is well tolerated in patients with good
      renal function and warrants further clinical evaluation.

PMID- 15737558
TI  - A phase I study of intraperitoneal topotecan in combination with intravenous
      carboplatin and paclitaxel in advanced ovarian cancer.
AB  - The aim of this study was to determine the maximum tolerated dose (MTD) of
      intraperitoneal (i.p.) topotecan combined with standard doses of intravenous
      (i.v.) carboplatin and paclitaxel and to investigate its pharmacokinetics. Women
      with primary ovarian cancer stage IIb - IV received six cycles of i.v.
      carboplatin and paclitaxel with escalating topotecan doses i.p. of 10, 15, 20 and
      25 mg/m(2). Twenty-one patients entered this trial. Febrile neutropenia,
      thrombocytopenia requiring platelet transfusion and fatigue grade 3 were dose
      limiting toxicities (DLT) at 25 mg/m(2) i.p. and 20 mg/m(2) i.p. of topotecan was
      considered to be the MTD. The mean plasma t(1/2) was 3.8 +/- 2.3 h for total
      topotecan and 4.4 +/- 3.9 h for active lactone. The area under the curve (AUC)
      was proportional with dose, R = 0.54, p < 0.05 for total topotecan and the
      peritoneal / plasma AUC ratio was 46 +/- 30. Fifteen patients who completed
      treatment had a median progression-free survival (PFS) of 27 months. In this
      setting the MTD of topotecan is 20 mg/m(2) i.p. The efficacy of this regimen
      should be explored further in a formal phase III study.

PMID- 15737559
TI  - Early detection of breast and ovarian cancer in families with BRCA mutations.
AB  - Women at risk of breast and ovarian cancer due to a genetic predisposition may
      opt for preventive surgery or surveillance. The aim of this study was to
      determine the effectiveness of surveillance in families with a BRCA mutation.
      Sixty-eight BRCA-families underwent surveillance using annual mammography,
      transvaginal ultrasound, and estimation of CA125. Two hundred and two women had
      at least one breast examination, and 138 at least one examination of the ovaries.
      After a mean follow-up of 33 months, breast cancer was detected in 21 women, four
      with lymph node metastases. After a mean follow-up of 37 months, six advanced
      ovarian cancers were detected. The percentage of metastatic breast cancers in the
      current study appeared to be acceptable. However, because these women have a high
      risk of developing breast cancer, they still have a substantial risk of
      developing metastatic disease under surveillance. Surveillance for ovarian cancer
      was not effective.

PMID- 15737560
TI  - Phase I investigation of recombinant anti-human vascular endothelial growth
      factor antibody in patients with advanced cancer.
AB  - We assessed the tolerability, safety, pharmacokinetics and dose-limiting toxicity
      (DLT) of the recombinant humanized IgG4 anti-vascular endothelial growth factor
      (VEGF) monoclonal antibody, HuMV833, in patients with advanced cancer. Cohorts of
      patients with progressive solid tumours received escalating doses of HuMV833 as a
      1-h intravenous (I.V.) infusion on days 1, 15, 22, and 29. Twenty patients
      (median Eastern Cooperative Oncology Group (ECOG) score 1) were accrued. HuMV833
      infusions were well tolerated and there were no grade III or IV toxicities
      definitely related to the antibody. Grade I or II toxicities probably related to
      the antibody included fatigue, dyspnoea and rash. There were two episodes of
      asymptomatic hypocalcaemia, one at grade III and one grade IV, which were
      recorded in early follow-up. There were eight grade I episodes of asymptomatic
      elevation of activated partial thromboplastin time (APTT) and two grade III
      events; one in a patient receiving 1 mg/kg and the other receiving extended doses
      of 10 mg/kg. Pharmacokinetic analysis revealed a non-linear kinetic and an
      elimination half-life of between 8.2 (0.3 mg/kg) and 18.7 (10 mg/kg) days. One
      patient with ovarian cancer experienced a partial response (PR) of 9 months
      duration and eight had disease stabilisation (SD) including one patient with
      colorectal carcinoma whose disease was stable for 14 months. In 13 of the 14
      samples taken from 12 patients, the plasma concentration of hepatocyte growth
      factor (HGF) was reduced 24 h after drug administration. HuMV833 is safe and
      lacked DLT at doses up to 10 mg/kg on this schedule. Multiple doses were well
      tolerated, despite occasional asymptomatic elevations in APTT. By combining
      pharmacokinetic, pharmacodynamic and toxicity data, we can identify doses of 1
      and 3mg/kg for further investigation. HuMV833 appears to possess some clinical
      activity.

PMID- 15737561
TI  - Has chemotherapy reached its limits in pediatric cancers?

PMID- 15737563
TI  - Management and outcome after local recurrence of osteosarcoma.
AB  - We report on the management and outcome of 96 patients who developed local
      recurrence (LR) after having definitive primary treatment with chemotherapy and
      surgery for non-metastatic osteosarcoma. LR developed at a median of 11 months
      from initial surgical treatment. 18% of patients had metastases prior to the
      diagnosis of LR and 23% were found to have metastases synchronously. The
      prognosis for this group with metastases was 14% survival at 2 years. In the 57
      patients without metastases at the time of development of LR, survival was 51% at
      2 years and 41% at 5 years. Treatment was by excision of the LR and radiotherapy
      or by amputation. The only significant prognostic factors identified were the
      presence of metastases at the time of development of LR (P < 0.0001) and small
      size of the LR. The role of adjuvant chemotherapy was unclear. Whilst every
      attempt should be made to avoid LR, patients who develop LR are curable,
      particularly if they do not have metastases at the time of diagnosis of the LR.

PMID- 15737564
TI  - Hypermethylation of CpG islands in the promoter region of the p15INK4B gene in
      childhood acute leukaemia.
AB  - It has been reported that the cyclin-dependent kinase inhibitor (CDKI) gene
      p15INK4B is frequently inactivated by genetic alterations and may be responsible
      for various malignant tumours. Another way of inactivation of this CDKI is by
      hypermethylation of 5'CpG islands in the promoter region of the p15INK4B gene and
      this inactivation seems to be a frequent event in various haematological
      malignancies. In the present study, we investigated the methylation status of the
      p151NK4B gene to clarify its role in the pathogenesis of childhood acute myeloid
      (AML) and acute lymphoblastic leukaemia (ALL). The study included 23 cases of B
      cell origin ALL, 13 cases of T-cell origin ALL, 32 cases of AML, and 10
      apparently healthy controls. Hypermethylation was studied by methylation-specific
      polymerase chain reaction. Hypermethylation of the p15INK4B gene was more
      frequent in cases with T-cell origin ALL (46.2%), but similar among children with
      B-cell origin ALL (13.0%) and AML (18.8%). Hypermethylation of p15INK4B may be
      involved in the pathogenesis of T-cell origin ALL, but not in that of AML or B
      cell origin ALL.

PMID- 15737565
TI  - Correlates of high-density mammographic parenchymal patterns by menopausal status
      in a rural population in Northern Greece.
AB  - Reproductive factors affect breast cancer risk, but less is known of their
      associations with mammographic density and whether these differ by menopausal
      status. We report on a cross-sectional study of 1946 pre- and 3047 post
      menopausal women who joined a breast screening programme in Northern Greece
      during 1993-1997. The odds of having a high-density Wolfe pattern (P2/DY) was
      inversely associated with age (P for linear trend <0.001) in both pre- and post
      menopausal women and, for post-menopausal women, with years since menopause (P <
      0.001). The odds of a P2/DY pattern declined with higher parity (P < 0.001) and
      younger age at first pregnancy (P = 0.05) in both pre- and post-menopausal women.
      They also decreased with the duration of breast-feeding in pre-menopausal women
      (P = 0.03 in pre- and P = 0.69 in post-menopausal women; test for interaction
      with menopausal status: P = 0.07). Age at menarche, age at menopause and the
      number of miscarriages/abortions were not associated with mammographic density.
      Age at first pregnancy and parity were strong correlates of mammographic density
      in pre- and post-menopausal women while duration of breast-feeding appeared to be
      particularly important in pre-menopausal women.

PMID- 15737566
TI  - European multi-centre case-control study on risk factors for rare cancers of
      unknown aetiology.
AB  - To search for occupational risk factors, we conducted a case-control study in
      nine European countries of cancers of the small intestine, male gall bladder,
      thymus, bone, male breast, melanoma of the eye, and mycosis fungoides.
      Recruitment was population based in Denmark, Latvia, France, Germany, Italy, and
      Sweden, from hospital areas in Spain and Portugal, and from one United Kingdom
      (UK) hospital. We recruited 1457 cases (84% interviewed). Numbers identified
      corresponded to those in the EUROCIM database for Denmark, but were below those
      observed for France, Italy and Sweden in the database. We recruited 3374
      population (61% interviewed) and 1284 colon cancer controls (86% interviewed). It
      was possible to undertake this complicated study across Europe, but we
      encountered three main problems. It was difficult to ensure complete case
      ascertainment, for population controls, we found a clear divide in the response
      rate from 75% in the South to only 55% in the North, and a somewhat selective
      recruitment was noted for the colon cancer controls. The study showed there is a
      clear dose-response relationship between alcohol intake and the risk of male
      breast cancer, and an excess risk of mycosis fungoides among glass formers,
      pottery and ceramic workers. Further data are expected.

PMID- 15737568
TI  - Antisense oligonucleotide-mediated inhibition of hTERT, but not hTERC, induces
      rapid cell growth decline and apoptosis in the absence of telomere shortening in
      human prostate cancer cells.
AB  - Recent evidence points to a novel function of human telomerase reverse
      transcriptase (hTERT) in promoting tumour cell survival, which might be
      independent of the telomere-elongating activity of the enzyme. To test this
      hypothesis, we evaluated comparatively the effects of telomerase inhibition,
      accomplished through antisense oligonucleotide-mediated interference with hTERT
      or human telomerase RNA component (hTERC), on the proliferative potential of
      DU145 human prostate cancer cells. Exposure of cells to a 2'-O-methyl-RNA
      phosphorothioate oligonucleotide targeting a splicing site within hTERT pre-mRNA
      induced almost complete inhibition of telomerase activity as a consequence of a
      marked reduction of the hTERT mRNA expression level, an early decline of DU145
      cell growth and apoptotic cell death without any appreciable telomere shortening.
      Conversely, exposure of DU145 cells to a 2'-O-methyl-RNA phosphorothioate
      oligonucleotide targeting the template region of hTERC failed to interfere with
      cell proliferation in spite of the almost complete abrogation of telomerase
      activity. These results extend and corroborate earlier evidence in favour of an
      enzymatic activity-independent mechanism by which hTERT maintains tumour cell
      survival and proliferation.

PMID- 15737567
TI  - Thiopurine methyltransferase in acute lymphoblastic leukaemia: biochemical and
      molecular biological aspects.
AB  - Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme, catalysing S
      methylation of aromatic and heterocyclic sulphhydryl compounds. TPMT activities
      and genotypes have been determined in patients with acute lymphoblastic leukaemia
      (ALL) and in control children. Median red blood cell (RBC) TPMT activity in ALL
      patients at diagnosis was significantly lower than in controls (median 11.5
      pmol/10(7) RBC*hr; range 1.7-30.7; n = 191 vs. 14.6 pmol/10(7) RBC*hr; range 1.6
      50.7; n = 140). This reduction of TPMT activity in ALL patients was not due to
      differences in the frequency of mutations in the TPMT gene. In concordance with
      other authors, we found a higher TPMT activity during maintenance treatment with
      6-mercaptopurine (6MP) than at diagnosis and in controls. However, we observed
      that TPMT activity was already significantly increased after the induction
      therapy, before the patients received 6MP (median 17.5; range 3.9-40.3 pmol/10(7)
      RBC*hr; n = 139). In vitro experiments indicate that the early increase of TPMT
      activity during treatment may be explained by the use of antifolates, e.g.,
      methotrexate and trimethoprim.

PMID- 15737569
TI  - Imbalance of the mitochondrial pro- and anti-apoptotic mediators in neuroblastoma
      tumours with unfavourable biology.
AB  - It has been proposed that a lack of apoptosis plays an important role in
      neuroblastoma (NB) progression. We therefore screened cDNA array filters,
      including 198 apoptotic genes, in order to identify mRNA transcripts that are
      differentially expressed in tumours with unfavourable versus favourable biology.
      Twenty-one genes were analysed further using real-time reverse-transcriptase
      polymerase chain reaction (RT-PCR). Significantly lower levels of DNCL1 (PIN;
      P(c)(corrected) = 0.0054) and NTRK1 (TrkA; P(c) = 0.039) were found in NB tumours
      with unfavourable biology. In addition, BID, BCL2, APAF1, CASP2, CASP3 and CASP9
      were found to be preferentially expressed in tumours with favourable biology,
      whereas CDKN1A (p21), IL2RA, and MCL1, were found to be preferentially expressed
      in NB tumours with unfavourable biology. In conclusion, mRNA levels of
      transcripts encoding pro-apoptotic mediators of the mitochondrial apoptotic
      pathway were found to be expressed to a lower extent in tumours with unfavourable
      biology. Our data also suggest that the mitochondrial pathway is suppressed in
      advanced stages of NB tumours, due to an imbalance between anti-apoptotic and pro
      apoptotic mediators which is a finding that may have therapeutic significance.

PMID- 15737570
TI  - The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary
      tumours.
AB  - The aim of this study was to determine how the efficacy of tamoxifen is affected
      when combined with soy isoflavones. To address this, female Sprague-Dawley rats
      were placed on diets supplemented with tamoxifen, genistein, daidzein, or a
      combination of each isoflavone with tamoxifen; a week later mammary tumours were
      induced by 7,12 dimethylbenzanthracene. The most effective diet was the
      tamoxifen/daidzein combination. It reduced tumour multiplicity by 76%, tumour
      incidence by 35%, tumour burden by over 95%, and increased tumour latency by 62%
      compared with positive controls. The tamoxifen/daidzein combination diet was in
      all aspects more effective while the tamoxifen/genistein combination was less
      effective than the tamoxifen diet. The tamoxifen/daidzein diet significantly
      decreased 8-oxo-deoxyguanosine levels (an indicator of oxidative DNA damage) in
      the mammary glands. This study conclusively shows for the first time the
      combination of daidzein with tamoxifen produces increased protection against
      mammary carcinogenesis, while the combination of genistein with tamoxifen
      produces an opposing effect when compared with tamoxifen alone.

PMID- 15737572
TI  - DNA methylation and the expanding epigenetics of T cell lineage commitment.
AB  - During their development from progenitors, lymphocytes make a series of cell fate
      decisions. These decisions reflect and require changes in overall programs of
      gene expression. To maintain cellular identity, programs of gene expression must
      be iterated through mitosis in a heritable manner by epigenetic processes, which
      include DNA methylation, methyl-CpG-binding proteins, histone modifications,
      transcription factors and higher order chromatin structure. Current evidence is
      consistent with the notion that DNA methylation acts in concert with other
      epigenetic processes to limit the probability of aberrant gene expression and to
      stabilize, rather than to initiate, cell fate decisions. In particular, DNA
      methylation appears to be a non-redundant repressor of CD8 expression in TCR
      gammadelta T cells and Th2 cytokine expression in Th1 and CD8 T cells, and is
      required to enforce clonally restricted Ly49 and KIR gene expression in NK cells.
      However, most of our knowledge is derived from in vitro studies, and the
      importance of DNA methylation in memory cell lineage fidelity in vivo remains to
      be shown convincingly.

PMID- 15737573
TI  - The lambda5-VpreB1 locus--a model system for studying gene regulation during
      early B cell development.
AB  - The lambda5 and VpreB genes encode the components of the surrogate light-chain,
      which forms part of the pre-B cell receptor. In mouse, the lambda5 and VpreB1
      genes of mouse are closely linked and coordinately regulated by a locus control
      region (LCR). Activation of the genes in pro-B cells depends on the combined
      effects of early B cell factor (EBF) and the E2A factors E12 and E47. Silencing
      of lambda5 expression in mature B cells occurs through the action of Ikaros on
      the gene promoter where it may compete for binding of EBF and initiate the
      formation of a silent chromatin structure.

PMID- 15737574
TI  - Assembly of silent chromatin during thymocyte development.
AB  - Epigenetic events that contribute to the assembly and maintenance of silent
      chromatin structures have been defined through genetic, molecular, and
      cytological studies in a variety of eukaryotic model organisms. However, the
      precise cascade of events responsible for converting a developmentally regulated
      gene from an active euchromatic state to a heritably silent heterochromatic state
      remains to be elucidated. To establish a molecular framework for studying this
      cascade, we examined the temporal order of events associated with silencing of
      the murine terminal transferase (Dntt) gene during thymocyte maturation. This
      article describes our findings in the context of current knowledge of gene
      silencing mechanisms.

PMID- 15737575
TI  - Immunoglobulin locus silencing and allelic exclusion.
AB  - Lymphocytes are characterised by monoclonal expression of antigen receptors. This
      is achieved by silencing of one of two homologous antigen receptor alleles, a
      process known as allelic exclusion. This process is regulated both before and
      after V(D)J recombination, by a variety of mechanisms. These include nuclear
      localisation, changes in chromatin structure and histone modifications, non
      coding sense and antisense RNA transcription, epigenetic alterations at the DNA
      level, feedback signalling from expressed alleles, locus contraction and
      decontraction, recruitment to heterochromatin. This review will focus on recent
      advances in the immunoglobulin heavy and kappa light chain loci. The current
      picture is of a complex, temporally ordered sequence of events, in which these
      loci share many contributory mechanisms, but clear and intriguing differences are
      emerging.

PMID- 15737576
TI  - MicroRNAs as regulators of mammalian hematopoiesis.
AB  - MicroRNAs (miRNAs) are an abundant class of approximately 22 nucleotide non
      coding RNAs and play important regulatory roles in animal and plant development
      at the post-transcriptional level. Many miRNAs cloned from mouse bone marrow
      cells are differentially regulated in various hematopoietic lineages, suggesting
      that they might influence hematopoietic lineage differentiation. miR-181, a miRNA
      specifically expressed in B cells within mouse bone marrow, promotes B-cell
      differentiation when expressed in hematopoietic stem/progenitor cells. Some human
      miRNAs are linked to leukemias: the miR-15a/miR-16 locus is frequently deleted or
      down-regulated in patients with B-cell chronic lymphocytic leukemia and miR-142
      is at a translocation site found in a case of aggressive B-cell leukemia.
      Collectively, these results indicate that miRNAs may be important regulators of
      mammalian hematopoiesis. Here, we provide background on the biogenesis and
      function of miRNAs and discuss how miRNA-mediated post-transcriptional regulation
      may influence the development and function of blood cells.

PMID- 15737577
TI  - Epigenetic control of B cell differentiation.
AB  - Gene expression, differentiation and the specialized function of various cell
      types are controlled epigenetically by post-translational histone modifications.
      These modifications establish a "histone code" that is recognized by various
      regulatory proteins, thereby creating a stable pattern of gene expression. The
      focus of this review is to discuss how the chromatin modifications regulate
      immunoglobulin gene rearrangement and B cell differentiation.

PMID- 15737578
TI  - Improving phylogenetic inference of mushrooms with RPB1 and RPB2 nucleotide
      sequences (Inocybe; Agaricales).
AB  - Approximately 3000 bp across 84 taxa have been analyzed for variable regions of
      RPB1, RPB2, and nLSU-rDNA to infer phylogenetic relationships in the large
      ectomycorrhizal mushroom genus Inocybe (Agaricales; Basidiomycota). This study
      represents the first effort to combine variable regions of RPB1 and RPB2 with
      nLSU-rDNA for low-level phylogenetic studies in mushroom-forming fungi.
      Combination of the three loci increases non-parametric bootstrap support,
      Bayesian posterior probabilities, and resolution for numerous clades compared to
      separate gene analyses. These data suggest the evolution of at least five major
      lineages in Inocybe-the Inocybe clade, the Mallocybe clade, the Auritella clade,
      the Inosperma clade, and the Pseudosperma clade. Additionally, many clades nested
      within each major lineage are strongly supported. These results also suggest the
      family Crepiodataceae sensu stricto is sister to Inocybe. Recognition of Inocybe
      at the family level, the Inocybaceae, is recommended.

PMID- 15737579
TI  - Eccrinales (Trichomycetes) are not fungi, but a clade of protists at the early
      divergence of animals and fungi.
AB  - The morphologically diverse orders Eccrinales and Amoebidiales have been
      considered members of the fungal class Trichomycetes (Zygomycota) for the last 50
      years. These organisms either inhabit the gut or are ectocommensals on the
      exoskeleton of a wide range of arthropods--Crustacea, Insecta, and Diplopoda--in
      varied habitats. The taxonomy of both orders is based on a few micromorphological
      characters. One species, Amoebidium parasiticum, has been axenically cultured and
      this has permitted several biochemical and phylogenetic analyses. As a
      consequence, the order Amoebidiales has been removed from the Trichomycetes and
      placed in the class Mesomycetozoea. An affinity between Eccrinales and
      Amoebidiales was first suggested when the class Trichomycetes was erected by
      Duboscq et al. [Arch. Zool. Exp. Gen. 86 (1948) 29]. Subsequently, molecular
      markers have been developed to study the relationship of these orders to other
      groups. Ribosomal gene (18S and 28S) sequence analyses generated by this study do
      not support a close association of these orders to the Trichomycetes or to other
      fungi. Rather, Eccrinales share a common ancestry with the Amoebidiales and
      belong to the protist class Mesomycetozoea, placed at the animal-fungi boundary.

PMID- 15737580
TI  - Molecular phylogeny of Vipera Laurenti, 1768 and the related genera Macrovipera
      (Reuss, 1927) and Daboia (Gray, 1842), with comments about neurotoxic Vipera
      aspis aspis populations.
AB  - We used mtDNA sequences (cytochrome b and NADH dehydrogenase subunit 2) to
      reconstruct molecular phylogenies of Vipera sensu lato, Vipera sensu stricto, and
      Vipera aspis. Three major clades were identified within the Vipera s.l. group:
      (1) the European vipers, (2) the oriental vipers, consisting of Montivipera
      (Vipera 2) plus Macrovipera lebetina, and (3) a group of Asian and North African
      vipers consisting of Daboia russelii, V. palaestinae, and Macrovipera
      mauritanica. We also distinguished three clades within the monophyletic European
      Vipera group: V. ammodytes, V. aspis, and V. latastei, and Pelias with monophyly
      of Vipera 1 uncertain. Within V. aspis, the specimens collected in France formed
      the sister group of an Italian clade. The "neurotoxic" French population of V.
      aspis, which has a specific venom profile, separated from other French V. aspis
      early in the history of this group.

PMID- 15737581
TI  - Phylogenetic relationships in Ephedra (Ephedraceae) inferred from chloroplast and
      nuclear DNA sequences.
AB  - Sequences of the nuclear ribosomal DNA internal transcribed spacer region 1 and
      the chloroplast-encoded genes maturase K and ribulose-1,5 biphosphate carboxylase
      large subunit were obtained from species of Ephedra (Ephedraceae) representing
      the geographic range and morphological diversity of the genus. Phylogenetic
      analyses of the DNA data indicate that relationships within the genus are better
      predicted by geographic region of origin than by ovulate cone characters. The
      sampled species with dry, winged (versus fleshy) ovulate cone bracts or single
      seeded cones do not form monophyletic groups and therefore the previous
      classification systems of Ephedra based on these aspects of bract morphology
      appear to be largely unnatural. Three groups were identified among the Old World
      species studied, one comprising European and Mediterranean species and two
      including only Asian species. The sequence data suggest a possible early
      divergence of a New World clade of Ephedra from among the Old World groups. The
      South American species form a distinct clade apparently related to one of two
      groups of North American species, which accords with a frequent floristic pattern
      of close relationships between species groups in western South America and
      southwestern North America.

PMID- 15737582
TI  - Multi-gene phylogenies indicate ascomal wall morphology is a better predictor of
      phylogenetic relationships than ascospore morphology in the Sordariales
      (Ascomycota, Fungi).
AB  - Ascospore characters have commonly been used for distinguishing ascomycete taxa,
      while ascomal wall characters have received little attention. Although taxa in
      the Sordariales possess a wide range of variation in their ascomal walls and
      ascospores, genera have traditionally been delimited based on differences in
      their ascospore morphology. Phylogenetic relationships of multiple
      representatives from each of several genera representing the range in ascomal
      wall and ascospore morphologies in the Sordariales were estimated using partial
      nuclear DNA sequences from the 28S ribosomal large subunit (LSU), beta-tubulin,
      and ribosomal polymerase II subunit 2 (RPB2) genes. These genes also were
      compared for their utility in predicting phylogenetic relationships in this group
      of fungi. Maximum parsimony and Bayesian analyses conducted on separate and
      combined data sets indicate that ascospore morphology is extremely homoplastic
      and not useful for delimiting genera. Genera represented by more than one species
      were paraphyletic or polyphyletic in nearly all analyses; 17 species of
      Cercophora segregated into at least nine different clades, while six species of
      Podospora occurred in five clades in the LSU tree. However, taxa with similar
      ascomal wall morphologies clustered in five well-supported clades suggesting that
      ascomal wall morphology is a better indicator of generic relationships in certain
      clades in the Sordariales. The RPB2 gene possessed over twice the number of
      parsimony-informative characters than either the LSU or beta-tubulin gene and
      consequently, provided the most support for the greatest number of clades.

PMID- 15737583
TI  - Phylogenetic relationships of salangid fishes (Osmeridae, Salanginae) with
      comments on phylogenetic placement of the salangids based on mitochondrial DNA
      sequences.
AB  - We used partial DNA sequences of cytochrome b and 16S mitochondrial genes to
      determine the phylogenetic placement of salangid fishes and the generic
      relationships within the salangids. Our molecular data strongly support the
      monophyly of salangid fishes, the inclusion of salangids in the Osmeridae, and
      the sister group relationship between salangids and osmerids. Our analyses
      suggest that Plecoglossus can be separated from all the other salangids and
      osmerids. Mallotus and Hypomesus are clustered within Osmerinae, rather than
      allied with Salanginae. As regards the relationships within the salangids, our
      analyses are incongruent with all previous classification hypotheses. Our
      phylogenetic analyses support the sister group relationships between Protosalanx
      and Neosalanx, and between Salanx and Hemisalanx. More evidences show that
      Leucosoma is more closely related to the Salanx-Hemisalanx clade, while
      Salangichthys forms part of an unresolved basal polytomy.

PMID- 15737584
TI  - The phylogenetic history and biogeography of the frankincense and myrrh family
      (Burseraceae) based on nuclear and chloroplast sequence data.
AB  - Generalized hypotheses for the vicariant, Gondwanan origin of pantropically
      distributed eudicotyledon families must be refined to accommodate recently
      revised dates that indicate major continental rifting events predate the
      evolution of many tricolpate angiosperm clades. Here, we use molecular
      phylogenies of an eudicotyledon family previously hypothesized to have a
      Gondwanan origin, the Burseraceae, to test this and other alternative
      biogeographical hypotheses in light of recalibrated geological events.
      Phylogenies based on nuclear and chloroplast data were reconstructed for 13 of
      the 18 genera (50 spp. total) of Burseraceae using parsimony, maximum likelihood,
      and Bayesian methods. Ages of all lineages were estimated using penalized
      likelihood and semiparametric rate smoothing [Bioinformatics 2003 (19) 301],
      which allows the user to calibrate phylogenies based on non-clock-like DNA
      sequence data with fossil information. Biogeographical hypotheses were tested by
      comparing ages of species and more inclusive lineages with their extant and most
      parsimonious ancestral distributions. Our data support a North American Paleocene
      origin for the Burseraceae followed by dispersal of ancestral lineages to eastern
      Laurasia and Southern Hemisphere continents.

PMID- 15737585
TI  - Nuclear ribosomal DNA and karyotypes indicate a NW African origin of South
      American Hypochaeris (Asteraceae, Cichorieae).
AB  - Hypochaeris has a disjunct distribution, with more than 15 species in the
      Mediterranean region, the Canary Islands, Europe, and Asia, and more than 40
      species in South America. Previous studies have suggested that the New World taxa
      have evolved from ancestors similar to the central European H. maculata. Based on
      internal transcribed spacer (ITS) sequences and fluorescence in situ
      hybridization (FISH) with 5S and 18S-25S rDNA of the previously overlooked
      Hypochaeris angustifolia from Moyen Atlas, Morocco, we show that it is sister to
      the entire South American group. A biogeographic analysis supports the hypothesis
      of long-distance dispersal from NW Africa across the Atlantic Ocean for the
      origin of the South American taxa rather than migration from North America,
      through the Panamian land bridge, followed by subsequent extinction in North
      America. With the assumption of a molecular clock, the trans-Atlantic dispersal
      from NW Africa to South America is roughly estimated to have taken place during
      Pliocene or Pleistocene.

PMID- 15737586
TI  - Alu insertion loci and platyrrhine primate phylogeny.
AB  - Short INterspersed Elements (SINEs) make very useful phylogenetic markers because
      the integration of a particular element at a location in the genome is
      irreversible and of known polarity. These attributes make analysis of SINEs as
      phylogenetic characters an essentially homoplasy-free affair. Alu elements are
      primate-specific SINEs that make up a large portion of the human genome and are
      also widespread in other primates. Using a combination wet-bench and
      computational approach we recovered 190 Alu insertions, 183 of which are specific
      to the genomes of nine New World primates. We used these loci to investigate
      branching order and have produced a cladogram that supports a sister relationship
      between Atelidae (spider, woolly, and howler monkeys) and Cebidae (marmosets,
      tamarins, and owl monkeys) and then the joining of this two family clade to
      Pitheciidae (titi and saki monkeys). The data support these relationships with a
      homoplasy index of 0.00. In this study, we report one of the largest applications
      of SINE elements to phylogenetic analysis to date, and the results provide a
      robust molecular phylogeny for platyrrhine primates.

PMID- 15737587
TI  - Phylogeny and molecular evolution of the tribe Harpalini (Coleoptera, Carabidae)
      inferred from mitochondrial cytochrome-oxidase I.
AB  - The tribe Harpalini is a group of ground beetles with a world-wide distribution
      that comprises approximately 2000 species and about 238 genera and subgenera.
      Hypotheses about the phylogenetic relationships of the subtribes of Harpalini are
      implicit within the systematic criteria put forward by different authors. A 759
      bp fragment of the mitochondrial COI was sequenced in 119 specimens (107 species)
      of 52 genera and subgenera that represent the main lineages of Harpalines, and 3
      species of other tribes used as outgroups. A hierarchical study of sequence
      divergence (under uncorrected and corrected models) and ts:tv ratio pattern
      analyses were carried out at different taxonomic levels. A low saturation rate
      was detected at first and second codon positions, whereas A+T richness causes a
      low transitions:transversions ratio, which suggests--a priori--a high rate of
      saturation at the third codon position. A progressive accumulation of sequence
      divergence and a decreasing ts:tv ratio were found from lower to higher taxonomic
      levels. MP strict consensus, ML, and minimum evolution distance (under ts+tv and
      tv only schemes) trees showed similar major clades within the tribe. The subtribe
      Ditomina is a monophyletic lineage with close affinities to the subtribe
      Harpalina. Harpalina is a polyphyletic lineage as the genus Daptus is always
      related to members of the subtribe Stenolophina, and the Selenophorines resulted
      a polyphyletic group related to the subtribe Anisodactylina. Main lineages
      proposed by Noonan [Quaest. Entomol. 9 (1973) 266] within the subtribe
      Anisodactylina have been corroborated in this study. The Australian genus
      Phorticosomus is not related to Ditomina but to the Australian Notiobioids
      lineage. Most taxa of the subtribe Stenolophina are always included in the same
      clade, together with taxa of the subtribe Pelmatellina, which might be considered
      as a lineage of Stenolophina related to Bradycellus and Dicheirotrichus. The
      subtribe Amblystomina lacks a well-supported relationship to the other subtribes
      of Harpalini and could not be consistently related to any of them.

PMID- 15737588
TI  - A multi-gene phylogeny of aquiline eagles (Aves: Accipitriformes) reveals
      extensive paraphyly at the genus level.
AB  - The phylogeny of the tribe Aquilini (eagles with fully feathered tarsi) was
      investigated using 4.2 kb of DNA sequence of one mitochondrial (cyt b) and three
      nuclear loci (RAG-1 coding region, LDH intron 3, and adenylate-kinase intron 5).
      Phylogenetic signal was highly congruent and complementary between mtDNA and
      nuclear genes. In addition to single-nucleotide variation, shared deletions in
      nuclear introns supported one basal and two peripheral clades within the
      Aquilini. Monophyly of the Aquilini relative to other birds of prey was
      confirmed. However, all polytypic genera within the tribe, Spizaetus, Aquila,
      Hieraaetus, turned out to be non-monophyletic. Old World Spizaetus and
      Stephanoaetus together appear to be the sister group of the rest of the Aquilini.
      Spizastur melanoleucus and Oroaetus isidori are nested among the New World
      Spizaetus species and should be merged with that genus. The Old World 'Spizaetus'
      species should be assigned to the genus Nisaetus (Hodgson, 1836). The sister
      species of the two spotted eagles (Aquila clanga and Aquila pomarina) is the
      African Long-crested Eagle (Lophaetus occipitalis). Hieraaetus
      fasciatus/spilogaster are closest to Aquila verreauxii and should be merged with
      that genus. Wahlberg's Eagle H. wahlbergi, formerly placed in Aquila, is part of
      a clade including three small Hieraaetus species (pennatus, ayresii, and
      morphnoides). The Martial Eagle (Polemaetus bellicosus) is the sister species of
      the Aquila/Hieraaetus/Lophaetus clade. Basal relationships within this clade
      remained unresolved. Parsimony reconstruction of the evolution of plumage pattern
      within Aquilini suggests that: (1) transverse barring of parts of the body
      plumage was lost in the Palearctic Aquila-Hieraaetus clade, (2) pale underparts
      in adult plumage evolved three times independently, and (3) dimorphic adult
      plumage is a derived character of the small-bodied Hieraaetus clade.

PMID- 15737589
TI  - Nuclear ribosomal DNA internal transcribed spacer 1 (ITS1) in Picea (Pinaceae):
      sequence divergence and structure.
AB  - The nrDNA ITS1 of Picea is 2747-3271 bp, the longest known of all plants. We
      obtained 24 cloned ITS1 sequences from six individuals of Picea glehnii, Picea
      mariana, Picea orientalis, and Picea rubens. Mean sequence divergence within
      these individuals (0.018+/-0.009) is more than half that between the species
      (0.031+/-0.011) and may be maintained against concerted evolution by separation
      of Picea 18S-26S rDNA repeats on multiple chromosomes. Picea ITS1 contains three
      subrepeats with a motif (5'-GGCCACCCTAGTC) that is conserved across Pinaceae. Two
      subrepeats are tandem, remote from the third, and more closely related and
      significantly more similar to one another than either is to the third subrepeat.
      This correlation between similarity and proximity may be the result of subrepeat
      duplication or concerted evolution within rDNA repeats. In inferred secondary
      structures, subrepeats generally form long hairpins, with a portion of the
      Pinaceae conserved motif in the terminal loop, and tandem subrepeats pair with
      one another over most of their length. Coalescence of ITS1 sequences occurs in P.
      orientalis but not in the other species.

PMID- 15737590
TI  - Poxvirus genome evolution by gene gain and loss.
AB  - The poxviruses (Poxviridae) are a family of viruses with double-stranded DNA
      genomes and substantial numbers (often >200) of genes per genome. We studied the
      patterns of gene gain and loss over the evolutionary history of 17 poxvirus
      complete genomes. A phylogeny based on gene family presence/absence showed good
      agreement with families based on concatenated amino acid sequences of conserved
      single-copy genes. Gene duplications in poxviruses were often lineage specific,
      and the most extensively duplicated viral gene families were found in only a few
      of the genomes analyzed. A total of 34 gene families were found to include a
      member in at least one of the poxvirus genomes analyzed and at least one animal
      genome; in 16 (47%) of these families, there was evidence of recent horizontal
      gene transfer (HGT) from host to virus. Gene families with evidence of HGT
      included several involved in host immune defense mechanisms (the MHC class I,
      interleukin-10, interleukin-24, interleukin-18, the interferon gamma receptor,
      and tumor necrosis factor receptor II) and others (glutaredoxin and glutathione
      peroxidase) involved in resistance of cells to oxidative stress. Thus "capture"
      of host genes by HGT has been a recurrent feature of poxvirus evolution and has
      played an important role in adapting the virus to survive host antiviral defense
      mechanisms.

PMID- 15737591
TI  - Origin, divergence, and phylogeny of epichloe endophytes of native Argentine
      grasses.
AB  - The epichloe endophytes are systemic, constitutive, and often vertically
      transmitted fungal symbionts of grass species in subfamily Pooideae. Prior
      studies indicate that several asexual epichloe endophytes (Neotyphodium species)
      have evolved directly from sexual (Epichloe) species, whereas others evolved by
      hybridization between two or more endophyte species. In this paper, we
      investigate the phylogenies of 27 Neotyphodium spp. isolates from 10 native grass
      species (in 4 tribes) in 22 populations throughout Argentina. Relationships among
      these fungi and a worldwide collection of epichloe endophytes were estimated by
      phylogenetic analysis of sequences from variable portions (mainly introns) of
      genes for beta-tubulin (tub2) and translation elongation factor 1-alpha (tef1).
      Most of the Argentine endophyte isolates were interspecific hybrids of Epichloe
      festucae and E. typhina. Only one isolate was a hybrid of a different ancestry,
      and three isolates were apparently non-hybrid endophytes. These results indicate
      that interspecific hybridization, which promotes genetic variation, was common
      during the evolution of the endophytes of Argentine grasses.

PMID- 15737592
TI  - Phylogenetics of wigeons and allies (Anatidae: Anas): the importance of sampling
      multiple loci and multiple individuals.
AB  - Species-level DNA phylogenies frequently suffer from two shortcomings--gene trees
      usually are constructed from a single locus, and often species are represented by
      only one individual. To evaluate the effect of these two shortcomings, we tested
      phylogenetic hypotheses within the wigeons and allies, a clade of Anas ducks
      (Anatidae) composed of five species. We sequenced two nuclear introns from the Z
      chromosome-linked chromo-helicase binding protein gene (CHD1Zb and CHD1Za) and
      the mitochondrial DNA (mtDNA) control region for multiple individuals sampled
      from widespread geographic locations. We compared these phylogenies to previously
      published phylogenies constructed from morphology and protein coding regions of
      mtDNA. Relative to other nuclear introns, CHD showed remarkable phylogenetic
      utility. Of the 26 CHD1Zb alleles identified, only one was shared between two
      species, and the combined CHD datasets revealed that four of the five species
      were consistent with monophyly. Several species shared mtDNA haplotypes, which
      probably was a result of interspecific hybridization. Overall, the nuclear CHD
      tree and the mtDNA tree were more congruent with coding regions of mtDNA than
      they were with morphology.

PMID- 15737593
TI  - The phylogenetic history of New World monkey beta globin reveals a platyrrhine
      beta to delta gene conversion in the atelid ancestry.
AB  - Orthologues of the beta globin gene locus from 10 New World monkey species were
      sequenced and aligned against available beta and delta globin sequences from
      rabbit and other primates. Where needed, additional primate sequencing was
      performed. Phylogenetic analysis identified a beta to delta conversion in the
      stem of the Anthropoidea, stretching from the 3' part of the proximal promotor to
      the 5' start of intron 2, consistent with earlier findings. No further conversion
      appeared to have occurred in the descent of the catarrhines. Within the New World
      monkey lineage that led to spider monkey and other atelids, another shorter gene
      conversion was found, spanning adjacent parts of exon 1 and intron 1. The
      analysis also confirmed that galago beta had replaced galago delta, that an
      earlier loriform-specific gene conversion extended over intron 2, and that gene
      conversion throughout the main gene conversion region occurred in the tarsiiform
      lineage. Platyrrhine phylogenetic relationships were investigated with beta
      sequences restricted to those that were not involved in gene conversions. This
      phylogeny generally agreed with results from other nuclear genes. The one
      exception was that the beta sequences did not place the callitrichine clade
      within the Cebidae but weakly joined the callitrichine and atelid clades.

PMID- 15737594
TI  - Biodiversity hotspots: evolutionary origins of biodiversity in wrasses
      (Halichoeres: Labridae) in the Indo-Pacific and new world tropics.
AB  - Halichoeres is a widely distributed coral reef fish genus with high levels of
      biodiversity in both the Indo-Pacific and New World tropics. This study employed
      molecular phylogenetic techniques and biogeographic analyses on 1700-1800 bp of
      mitochondrial CO1, 16s, and 12s to test competing hypotheses regarding the
      origins of biodiversity in this genus in these two biodiversity hotspots.
      Analyses indicate that Halichoeres is polyphyletic with distinct New World and
      Indo-Pacific Ocean components. The Halichoeres in the New World tropics formed a
      strongly supported clade (99% MP, 100% ML bootstrap values) that diverged 21.2
      18.1 mya, suggesting that this lineage may represent a relictual fauna of the
      ancient Tethys Sea. The closure of the Isthmus of Panama contributed to the
      creation of Halichoeres biodiversity, but diversification across the Isthmus
      prior to its closure and within the W. Atlantic after the closure 3.1 mya were
      also important processes creating biodiversity in the New World tropics. Within
      the Indonesian Australian Archipelago (IAA) analysis of age vs. geographic
      distribution supported neither Center of Origin, Center of Accumulation or Center
      of Overlap hypotheses, and molecular clock estimates indicated that the role of
      Pleistocene sea level changes in the origins of IAA marine biodiversity may be
      less important than previously thought. Ancestral distribution reconstructions
      within the Indo-West Pacific (IWP) clade (99% ML bootstrap value) also failed to
      support these hypotheses as the reconstructions were highly sensitive to the
      inclusion of missing taxa. Results suggest plueralistic origins of biodiversity,
      but that vast amounts of habitat may favor the survival of biodiversity in the
      IAA biodiversity hotspot.

PMID- 15737596
TI  - Falsifications and corroborations: Karl Popper's influence on systematics.
AB  - Over the last three decades, the philosophy of Karl Raimund Popper has had a
      strong influence on the field of systematic biology. Unequivocally, no other
      philosopher's work has had such an influence during this formative period in
      systematics. Much, but not all, of the early discourse on Popper and systematics
      dealt with the philosophical basis of systematics as a science. More recently
      Popper's work has been discussed in the systematics literature in relation to
      specific methodologies such as parsimony and maximum likelihood. In this paper,
      we provide the reader with a concise summary of Popper's ideas relevant to
      systematics, review the systematic literature invoking or declining Popper's
      importance to the field, and make a recommendation for the future course of
      philosophical thinking in systematics. We try to make clear various authors'
      interpretations of Popper's work and how those interpretations have impacted
      systematic thought. Although the reader may come away from this review with a
      clearer idea of Popper's relevance or lack thereof, our primary hope is that the
      reader will be compelled to question him- or herself about the philosophical
      basis of the systematic work that he or she does, and to delve into the
      literature herein cited. We begin by presenting a synopsis of Popper's
      philosophical views to allow those views to be placed in the context of
      systematics.

PMID- 15737595
TI  - Phylogeny of swallows (Aves: Hirundinidae) estimated from nuclear and
      mitochondrial DNA sequences.
AB  - The phylogeny of swallows was reconstructed by comparing segments of three genes,
      nuclear beta-fibrinogen intron 7 (betafib7), mitochondrial cytochrome b (cytb),
      and mitochondrial ND2, in a variety of combinations using maximum likelihood and
      Bayesian methods. betafib7 was sequenced for 47 species, cytb for 74 species, and
      ND2 for 61 species to yield comparisons among 75 of the 84 currently recognized
      swallow species. The family Hirundinidae was confirmed to consist of two clades,
      Pseudochelidoninae (river martins) and Hirundininae (typical swallows). The
      Hirundininae is further divided into mud nesters (Hirundo sensu lato), core
      martins (Phedina, Riparia, and New World endemic genera), and basal relicts
      (Psalidoprocne, Cheramoeca, and Pseudhirundo). We did not resolve the hierarchy
      among these three hirundinine groups, but discovered many relationships within
      them. Mud-nesting genera have the following relationships: (Hirundo sensu
      stricto, Ptyonoprogne), (Delichon, (Petrochelidon, Cecropis)). Core martins have
      the following topology: (Phedina, Riparia cincta), (Riparia sensu stricto,
      Tachycineta, ((Stelgidopteryx, Progne), (Neotropical endemic genera))).
      Interspecific relationships among the Neotropical endemics were resolved
      completely; Atticora and Notiochelidon are paraphyletic, and all Neotropical
      endemics probably should be lumped into one or two genera. The final group of
      hirundinines, the basal relicts, consists of a sister pair, the Australian
      Cheramoeca and African Pseudhirundo. The African saw-wings (Psalidoprocne) are
      their likely sister group.

PMID- 15737597
TI  - Evolutionary history of African lungfish: a hypothesis from molecular phylogeny.

PMID- 15737598
TI  - A phylogenetic analysis of Epimedium (Berberidaceae) based on nuclear ribosomal
      DNA sequences.

PMID- 15737599
TI  - Diversity and phylogenetic relationships of Hemidactylus geckos from the Comoro
      islands.

PMID- 15737600
TI  - Does elision account for molecular saturation: case study based on mitochondrial
      ribosomal DNA among Characiform fishes (Teleostei: Ostariophysii).

PMID- 15737601
TI  - Comments on the paper "Phylogeny of mysticete whales based on mitochondrial and
      nuclear data" by Amanda L. Rychel, Tod W. Reeder, and Annalisa Berta [Mol.
      Phylogenet. Evol. 32 (2004) 892-901].

PMID- 15737603
TI  - Do drug substrates enter the common drug-binding pocket of P-glycoprotein through
      "gates"?
AB  - Overexpression of P-glycoprotein (P-gp; ABCB1) can cause multidrug resistance
      during cancer and AIDS chemotherapy because of its ability to transport a broad
      range of structurally unrelated compounds from the cell. P-gp is a member of the
      ABC family of proteins. It is a single polypeptide containing four domains--two
      transmembrane (TM) domains each of which contains six TM segments, and two
      nucleotide-binding domains. Chemical modification and cross-linking studies of
      cysteine mutants of P-gp indicate that the common drug-binding pocket is at the
      interface between the TM domains. It has been postulated that drug substrates
      enter the lipid bilayer, are extracted by P-gp and transported to the
      extracellular medium. It is not clear how drug substrates enter the drug-binding
      pocket. Here, we propose that drug-substrates diffuse from the lipid bilayer into
      the drug-binding pocket through "gates" formed by TM segments at either end of
      the drug-binding pocket.

PMID- 15737604
TI  - Prestress mediates force propagation into the nucleus.
AB  - Several reports show that the nucleus is 10 times stiffer than the cytoplasm.
      Hence, it is not clear if intra-nuclear structures can be directly deformed by a
      load of physiologic magnitudes. If a physiologic load could not directly deform
      intra-nuclear structures, then signaling inside the nucleus would occur only via
      the mechanisms of diffusion or translocation. Using a synchronous detection
      approach, we quantified displacements of nucleolar structures in cultured airway
      smooth muscle cells in response to a localized physiologic load ( approximately
      0.4 microm surface deformation) via integrin receptors. The nucleolus exhibited
      significant displacements. Nucleolar structures also exhibited significant
      deformation, with the dominant strain being the bulk strain. Increasing the pre
      existing tensile stress (prestress) in the cytoskeleton significantly increased
      the stress propagation efficiency to the nucleolus (defined as nucleolus
      displacement per surface deformation) whereas decreasing the prestress
      significantly lowered the stress propagation efficiency to the nucleolus.
      Abolishing the stress fibers/actin bundles by plating the cells on poly-L-lysine
      coated dishes dramatically inhibited stress propagation to the nucleolus. These
      results demonstrate that the prestress in the cytoskeleton is crucial in
      mediating stress propagation to the nucleolus, with implications for direct
      mechanical regulation of nuclear activities and functions.

PMID- 15737605
TI  - A novel trehalose-synthesizing glycosyltransferase from Pyrococcus horikoshii:
      molecular cloning and characterization.
AB  - A gene (ORF PH1035), annotated to encode an uncharacterized hypothetical protein
      in Pyrococcus horikoshii, was first cloned and expressed in Escherichia coli. The
      recombinant enzyme was purified to homogeneity by Ni-NTA affinity chromatography
      and its molecular mass was determined to be 49,871Da by MALDI-TOF mass
      spectrometry. When the purified enzyme was reacted with nucleoside diphosphate
      glucoses including UDP-glucose as a donor and glucose, rather than glucose-6
      phosphate, as an acceptor, it specifically created a free trehalose. The enzyme
      was also able to partly hydrolyze the trehalose to glucose. The optimum pH was
      5.5 and the enzyme was highly stable from pH 6 to 8. The deduced amino acid
      sequence showed a high homology with that of the glycosyl transferase group 1
      (Pfam00534) in the BLAST search. The results suggest that the enzyme is a novel
      glycosyltransferase catalyzing the synthesis of the trehalose in the archaeon.

PMID- 15737606
TI  - Identification of single-chain antibody fragments specific against SARS
      associated coronavirus from phage-displayed antibody library.
AB  - To develop early diagnostic reagents, effective vaccines, and even drugs against
      SARS-associated coronavirus (SARS-CoV), the human single fold single-chain
      antibody fragments, (scFv) libraries I+J (Tomlinson I+J) were used to identify
      novel scFvs, which can specifically bind to SARS-CoV. Interestingly, two scFvs
      (B5 and B9) exhibited higher binding specificity to SARS-CoV with the OD(450)
      value 0.608 and 0.545, respectively, and their coding sequences shared the
      identical sequence composed of V(H) gene (351bp) and V(L) gene (327bp), so the
      two scFvs were uniformly named as SA59B and chosen for further analysis. SA59B
      scFv was expressed in soluble form in Escherichia coli HB2151 and purified by
      immobilized metal affinity chromatography. The soluble 30kDa SA59B scFv-antibody
      was verified in SDS-PAGE and Western-blot. The purified SA59B scFv-antibody was
      labeled with HRP by the glutaraldehyde method, and the concentration of HRP and
      SA59B scFv-antibody in the SA59B-HRP solution reached 2.4 and 2.28mg/ml,
      respectively. Then, the binding ability of SA59B-HRP to SARS-CoV was evaluated by
      ELISA with S/N of 11.6, indicating higher binding specificity between them.
      Finally, both the SA59B sequence specificity and its application for diagnosis,
      prophylaxis or therapy of SARS were discussed.

PMID- 15737607
TI  - Carboxy-monopeptidase substrate specificity of human cathepsin X.
AB  - Cathepsin X is a papain-like cysteine protease with restricted positional
      specificity, acting primarily as a carboxy-monopeptidase. We mapped the
      specificities at the S2, S1, and S1' subsites of human cathepsin X by
      systematically and independently substituting the P2, P1, and P1' positions of
      the carboxy-monopeptidase substrate Abz-FRF(4NO(2)) with natural amino acids.
      Human cathepsin X has broad S2, S1, and S1' specificities within two orders of
      magnitude in k(cat)/K(M), excluding proline that is not tolerated at these
      subsites. Glycine is not favored in S2, but is among the preferred residues in S1
      and S1', which highlights S2 as the affinity-determinant subsite. The presence of
      peculiar residues at several binding site positions (Asp76, His234, Asn75, and
      Glu72) does not translate into a markedly different sequence specificity profile
      relative to other human cathepsins. These findings suggest that a specific
      function of human cathepsin X is unlikely to result from sequence specificity,
      but rather from a combination of its unique positional specificity and the co
      localization of enzyme and substrate in a specific cellular environment.

PMID- 15737608
TI  - Engineering the E. coli beta-galactosidase for the screening of antiviral
      protease inhibitors.
AB  - Site-specific proteolysis is essential in many fundamental cellular and viral
      processes. It has been previously shown that the Escherichia coli beta
      galactosidase can be useful for the high-throughput screening of human
      immunodeficiency virus type 1 protease inhibitors. Here, by using
      crystallographic and functional data of the bacterial enzyme, we have identified
      a new accommodation site between amino acids 581 and 582, in a solvent-exposed
      and flexible beta-turn of domain III. The placement of the model peptide
      reproducing the matrix-capsid (p17/p24) gag cleavage sequence renders a highly
      active and efficiently digested chimeric construct. The use of this insertion
      site, that increases the cleavage potential of this reporter enzyme, can improve
      the sensitivity and dynamic range of the antiviral drug assay. This simple and
      highly specific analytical test may also be extended to the screening of other
      specific protease inhibitors by a convenient colorimetric assay.

PMID- 15737609
TI  - Molecular cloning, functional expression, and molecular modeling of bothrostatin,
      a new highly active disintegrin from Bothrops jararaca venom.
AB  - Disintegrins are among the most potent antagonists of several integrins. A cDNA
      encoding a novel disintegrin, bothrostatin, was cloned from a Bothrops jararaca
      cDNA library. The precursor of bothrostatin contains a pro, a metalloproteinase,
      and an RGD-disintegrin domain. The disintegrin domain expressed in Escherichia
      coli showed high inhibitory activity on collagen-induced platelet aggregation
      (IC(50) of 12nM), and thus it can be used as a useful tool for studies of
      integrin-ligand interaction. Furthermore, we used the comparative modeling
      approach to obtain a model of the 3D structure of bothrostatin. Our results
      suggest that bothrostatin adopts a globular, closed structure in solution. The
      RGD motif is exposed to the solution by the loop formed by residues 45-59 and is
      very close to the C-terminal domain forming a finger-like structure. The
      proximity of the RGD loop and the C-terminal residues, which is maintained by the
      Cys47-Cys66 bond, suggests that the C-terminal residues are involved in the
      ability of bothrostatin to interact with its ligands.

PMID- 15737610
TI  - Diphtheria toxin translocation across cellular membranes is regulated by
      sphingolipids.
AB  - Diphtheria toxin is translocated across cellular membranes when receptor-bound
      toxin is exposed to low pH. To study the role of sphingolipids for toxin
      translocation, both a mutant cell line lacking the first enzyme in de novo
      sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of
      the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient
      cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin
      than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell
      line (CHO-K1), both when toxin translocation directly across the plasma membrane
      was induced by exposing cells with surface-bound toxin to low pH, and when the
      toxin followed its normal route via acidified endosomes into the cytosol. Toxin
      binding was similar in these three cell lines. Furthermore, inhibition of serine
      palmitoyltransferase activity by addition of myriocin sensitized the two control
      cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no
      effect was observed in cells lacking serine palmitoyltransferase (LY-B). In
      conclusion, diphtheria toxin translocation is facilitated by depletion of
      membrane sphingolipids.

PMID- 15737611
TI  - Sphingolipid-to-glycerophospholipid conversion in SPL-null cells implies the
      existence of an alternative isozyme.
AB  - Sphingosine-1-phosphate (S1P) lyase catalyzes the cleavage of the bioactive lipid
      molecule S1P to phosphoethanolamine and hexadecenal, both of which are utilized
      as glycerophospholipid precursors. Until now, only one gene, SPL, has been
      identified as encoding a S1P lyase. In the present study, SPL-null F9 cells were
      able to convert radiolabeled dihydrosphingosine to glycerophospholipids, albeit
      at much lower efficiency than parent cells. Lysates prepared from the SPL-null
      cells exhibited weak but significant dihydrosphingosine-1-phosphate lyase
      activity in vitro. These results provide evidence of the existence of an
      alternative S1P lyase.

PMID- 15737612
TI  - Influence of membrane fluidity on human immunodeficiency virus type 1 entry.
AB  - For penetration of human immunodeficiency virus type 1 (HIV-1), formation of
      fusion-pores might be required for accumulating critical numbers of fusion
      activated gp41, followed by multiple-site binding of gp120 with receptors, with
      the help of fluidization of the plasma membrane and viral envelope. Correlation
      between HIV-1 infectivity and fluidity was observed by treatment of fluidity
      modulators, indicating that infectivity was dependent on fluidity. A 5% decrease
      in fluidity suppressed the HIV-1 infectivity by 56%. Contrarily, a 5% increase in
      fluidity augmented the infectivity by 2.4-fold. An increased temperature of 40
      degrees C or treatment of 0.2% xylocaine after viral adsorption at room
      temperature enhanced the infectivity by 2.6- and 1.5-fold, respectively. These
      were inhibited by anti-CXCR4 peptide, implying that multiple-site binding was
      accelerated at 40 degrees C or by xylocaine. Thus, fluidity of both the plasma
      membrane and viral envelope was required to form the fusion-pore and to complete
      the entry of HIV-1.

PMID- 15737613
TI  - Effects of PFOS and PFOA on L-type Ca2+ currents in guinea-pig ventricular
      myocytes.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are amphiphiles
      found ubiquitously in the environment, including wildlife and humans, and are
      known to have toxic effects on physiological functions of various tissues. We
      investigated the effects of PFOS and PFOA on action potentials and L-type Ca(2+)
      currents, I(CaL), in isolated guinea-pig ventricular myocytes using whole-cell
      patch-clamp recording. In current-clamp experiments, PFOS significantly decreased
      the rate of spike, action potential duration, and peak potential at doses over 10
      microM. In voltage-clamp experiments, PFOS increased the voltage-activated peak
      amplitude of I(CaL), and shifted the half-activation and inactivation voltages of
      I(CaL) to hyperpolarization. PFOA had similar effects PFOS, but showed
      significantly lower potency. These findings are consistent with previous
      observations for anionic n-alkyl surfactants, suggesting that PFOS and PFOA may
      change membrane surface potential, thereby eliciting general effects on calcium
      channels. These findings provide further insights into the mechanisms of PFOA and
      PFOS toxicities.

PMID- 15737614
TI  - Cis/trans heterogeneity of Gln30-Pro31 peptide bond determines whether a 79
      residue fragment of staphylococcal nuclease self-associates.
AB  - The self-association reaction of a 79-residue fragment of staphylococcal nuclease
      (SNase79) was studied by far-UV CD, size-exclusion chromatography, and
      heteronuclear multidimensional NMR spectroscopy. A large population of SNase79 is
      in self-associated state while a small population of SNase79 is essentially in a
      monomeric state. The sequence region Thr13-Val39 is responsible for association
      interface of SNase79. The trans-conformation of X-prolyl bond Gln30-Pro31 may
      make residues Tyr27-Gln30, serve as a folding nucleation site, and lead the
      segment Thr13-Val39 of SNase79 to adopt a native-like beta-sheet conformation,
      which results in the self-association of SNase79. The non-native conformation of
      the segment Thr13-Val39 of SNase79 associated with the cis-conformation of X
      prolyl bond Gln30-Pro31 may preclude SNase79 from the soluble aggregates.

PMID- 15737615
TI  - Functional expression of a multidrug P-glycoprotein transporter of Leishmania.
AB  - P-glycoprotein (Pgp) transporters play an important role in multidrug resistance
      in eukaryotic cells and in protozoan parasites such as Leishmania. To search for
      new reversal agents of the Leishmania tropica Pgp, we developed a screening assay
      using the Baculovirus-insect cell expression system. We demonstrated a MgATP
      dependent, vanadate-sensitive transport of Hoechst 33342 in membrane preparations
      of Sf9 insect cells expressing Pgp. We have found that dihydro-beta-agarofuran
      sesquiterpenes from Maytenus cuzcoina inhibited Hoechst 33342 transport that
      correlates with their reversal effect in a multidrug-resistant L. tropica line
      overexpressing Pgp. The results suggest that Sf9 cell membrane Hoechst 33342
      transport system represents an efficient tool for examining the interactions of
      Leishmania Pgp with pharmacological agents.

PMID- 15737616
TI  - Negative regulation of the expressions of cytokeratins 8 and 19 by SLUG repressor
      protein in human breast cells.
AB  - Invasiveness of tumor cells is often determined by the profile of their expressed
      genes. To determine the gene expression differences between an invasive and a non
      invasive human breast tumor cells, we selected BT-549 (invasive) and MDA-MB-468
      (non-invasive) cells, and compared their transcriptomes by cDNA microarray
      analysis. Among the significant differences in gene expressions, notable are the
      up-regulation of cytokeratins 8 and 19, and down-regulation of metallothioneins
      1G and IL in MDA-MB-468 cells. Since MDA-MB-468 cells do not express SLUG, a
      member of a small family of E2-box-binding zinc finger silencer proteins, we
      studied whether the cytokeratin gene overexpressions in these cells are due to
      the absence of SLUG. Inducible expression of SLUG in MDA-MB-468 cells inhibited
      the expressions of the cytokeratin 8 and 19 but not others as was revealed by
      microarray analysis. Similarly, siRNA knock down of SLUG in BT-549 cells
      increased the expressions of those cytokeratin mRNAs. SLUG levels in the cell
      regulated the function of cytokeratins 8 and 19 gene promoters. We conclude that
      the expressions of cytokeratins and metallothioneins may be associated with the
      differential invasive behaviors of these breast tumor cells and SLUG may have
      regulatory roles in this process.

PMID- 15737617
TI  - Influence of assembly of siRNA elements into RNA-induced silencing complex by
      fork-siRNA duplex carrying nucleotide mismatches at the 3'- or 5'-end of the
      sense-stranded siRNA element.
AB  - RNA interference (RNAi) is a powerful method for suppressing the expression of a
      gene of interest, and can be induced by 21-25 nucleotide small interfering RNA
      (siRNA) duplexes homologous to the silenced gene, which function as sequence
      specific RNAi mediators in RNA-induced silencing complexes (RISCs). In the
      previous study, it was shown that fork-siRNA duplexes, whose sense-stranded siRNA
      elements carried a few nucleotide mismatches at the 3'-ends against the antisense
      stranded siRNA elements, could enhance RNAi activity more than conventional siRNA
      duplexes in cultured mammalian cells. In this study, we further characterized
      fork-siRNA duplexes using reporter plasmids carrying target sequences
      complementary to the sense- or antisense-stranded siRNA elements in the
      untranslated region of Renilla luciferase. The data presented here suggest that
      nucleotide mismatches at either the 3'- or 5'-end of the sense-stranded siRNA
      elements in fork-siRNA duplexes could influence assembly of not only the
      antisense-stranded siRNA elements but also the sense-stranded elements into
      RISCs. In addition, we further suggest the possibility that there could be a
      positional effect of siRNA duplex on RNAi activity.

PMID- 15737618
TI  - The tumor suppressor DAL-1/4.1B modulates protein arginine N-methyltransferase 5
      activity in a substrate-specific manner.
AB  - We previously identified DAL-1/4.1B as a growth suppression protein involved in
      the pathogenesis of lung, breast, and meningioma tumors. Using yeast two-hybrid
      interaction cloning, protein arginine N-methyltransferase 3 (PRMT3) was
      originally identified as a DAL-1/4.1B-interacting protein. PRMTs catalyze the
      sequential transfer of methyl groups from S-adeonsyl-l-methionine to the
      guanidino nitrogens of arginine residues in proteins, the effect of which can
      include regulation of signal transduction, transcription regulation, and RNA
      transport, suggesting that modulating this event may have far-reaching impact. In
      this study, we assessed the impact of DAL-1/4.1B binding on the activity of
      another family member, PRMT5, both in vitro and in cells. In contrast to PRMT3,
      DAL-1/4.1B was found to mediate PRMT5 by either inhibiting (Sm proteins) or
      enhancing (myelin basic protein) protein methylation. We propose that this
      interaction between a tumor suppressor and a post-translational methylation
      enzyme is of biological importance in controlling tumorigenesis.

PMID- 15737619
TI  - The protein kinase inhibitor, staurosporine, inhibits L-type Ca2+ current in
      rabbit atrial myocytes.
AB  - A whole-cell patch recording was used to determine the effects of staurosporine
      (ST), a potent protein kinase C (PKC) inhibitor, on L-type Ca(2+) channel (LTCC)
      activity in rabbit atrial myocytes. Bath application of ST (300 nM) caused a
      significant reduction in peak I-V relationship of LTCC (from -16.8+/-2.55 to 
      3.74+/-1.22pApF(-1) at 0 mV). The level of L-type Ca(2+) current (I(Ca,L))
      inhibition produced by ST was independent of the voltage at which the effect was
      measured. ST inhibited the I(Ca,L) in a dose-dependent manner with a K(d) value
      of 61.98+/-6.802 nM. ST shifted the activation curve to more positive potentials,
      but did not have any significant effect on the voltage dependence of the
      inactivation curve. Other PKC inhibitors, GF 109203X (1 microM) and chelerythrine
      (3 microM), and PKA inhibitor, PKA-IP (5 microM), did not show any inhibitory
      effect on I(Ca,L). Additional application of ST in the presence of isoproterenol
      (1 microM), a selective beta-adrenoreceptor agonist, reduced peak I(Ca,L) (78.2%)
      approximately to the same level with single application of ST (77.8%). In
      conclusion, our results indicate that ST directly blocks the LTCC in a PKC or PKA
      independent manner on LTCC and it should be taken into consideration when ST is
      used in functional studies of ion channel modulation by protein phosphorylation.

PMID- 15737620
TI  - Reduction of PTP1B by RNAi upregulates the activity of insulin controlled fatty
      acid synthase promoter.
AB  - Metabolic deregulation accompanying type II diabetes is characterized by insulin
      resistance in peripheral tissues (liver, muscle, and adipose), mediated by
      impairments in insulin receptor (IR) signaling. Protein tyrosine phosphatase 1B
      (PTP1B) has been shown to be a negative regulator of IR autophosphorylation and
      thus has been considered as a major therapeutic target for the treatment of type
      II diabetes. We use RNA interference technique to downregulate PTP1B expression
      in hepatoma cell line. A secretory HBV s-antigen was introduced as reporter and
      driven by mouse fatty acid synthase promoter, which is positively controlled by
      insulin signaling. Liver-targeted hydrodynamic injection in tail vein was
      introduced to transfer siRNA (or siRNA expression vector) and reporter plasmid
      into mouse liver. On fasted/refed and glucose stimulation condition, the HBV s
      antigen in sera in RNAi group was higher than that in the negative group. Our
      results provided evidence that upregulation of insulin signaling by reducing
      PTP1B liver with RNAi can be a potent diabetes treatment method.

PMID- 15737621
TI  - Jumonji represses alpha-cardiac myosin heavy chain expression via inhibiting MEF2
      activity.
AB  - Expression of alpha-cardiac myosin heavy chain gene (alphaMHC) is developmentally
      regulated in normal embryonic hearts and down-regulated in cardiac myopathy and
      failing hearts. Jumonji (JMJ) has been shown to be critical for normal
      cardiovascular development and functions as a transcriptional repressor. Here, we
      demonstrate that JMJ represses alphaMHC expression through inhibition of myocyte
      enhancer factor 2 (MEF2) activity. In primary cardiomyocytes, overexpression of
      JMJ leads to marked reduction of endogenous alphaMHC expression. JMJ represses
      the synergistic activation of alphaMHC by MEF2 and thyroid hormone receptor (TR).
      Interestingly, JMJ inhibits transcriptional activities of all MEF2 isoforms, but
      not the TR-dependent activation. The transcriptional repression domain of JMJ
      interacts with the N-terminal part of MEF2A, resulting in the repression of MEF2A
      activities. These results suggest that JMJ represses alphaMHC expression via
      protein-protein interaction with MEF2A.

PMID- 15737622
TI  - A boundary for histone acetylation allows distinct expression patterns of the
      Ad4BP/SF-1 and GCNF loci in adrenal cortex cells.
AB  - Ad4BP/SF-1 is a nuclear receptor whose expression is restricted to tissues
      involved in steroid hormone synthesis such as the adrenal cortex and gonads.
      Recent sequence data analysis has shown that the Ad4BP/SF-1 gene is located only
      13kb downstream of the last exon of the neighboring GCNF gene that is expressed
      in some neurons and gonadal germ cells. Despite the close proximity of the two
      genes, regulatory elements from one do not interfere with the transcription of
      the neighboring gene, resulting in distinct expression patterns of Ad4BP/SF-1 and
      GCNF. This observation has led to the prediction that an insulator element must
      exist between the two loci to establish independent transcription units. We
      performed DNase I hypersensitivity assays on the adrenal cortex cell line, Y-1,
      to test for the existence of an insulator. Three hypersensitive sites were
      identified in the region spanning 2.1kb between the last exon of GCNF and the
      first exon of Ad4BP/SF-1. The most upstream site contains a binding site for
      CTCF, a known insulator protein, while the other sites are predicted to associate
      with the nuclear matrix. Chromatin immunoprecipitation analysis using anti
      acetylated histone H3 and H4 antibodies showed a discontinuous pattern of histone
      H3 and H4 acetylation upstream of these sites. Our data suggest that the
      chromatin architecture specialized by CTCF and the nuclear matrix contribute to
      the distinct pattern of transcriptional regulation of these genes.

PMID- 15737623
TI  - Kinetics of structural changes in the relay loop and SH3 domain of myosin.
AB  - The intrinsic fluorescence of smooth muscle myosin signals conformational changes
      associated with different catalytic states of the ATPase cycle. To elucidate this
      relationship, we have examined the pre-steady-state kinetics of nucleotide
      binding, hydrolysis, and product release in motor domain-essential light chain
      mutants containing a single endogenous tryptophan, either residue 512 in the
      rigid relay loop or residue 29 adjacent to the SH3 domain. The intrinsic
      fluorescence of W512 is sensitive to both nucleotide binding and hydrolysis, and
      appears to report structural changes at the active site, presumably through a
      direct connection with switch II. The intrinsic fluorescence of W29 is sensitive
      to nucleotide binding but not hydrolysis, and does not appear to be tightly
      linked with structural changes occurring at the active site. We propose that the
      SH3 domain may be sensitive to conformational changes in the lever arm through
      contacts with the essential light chain.

PMID- 15737624
TI  - Cyclic strain-mediated regulation of vascular endothelial cell migration and tube
      formation.
AB  - Hemodynamic forces exerted by blood flow (cyclic strain, shear stress) affect the
      initiation and progression of angiogenesis; however, the precise signaling
      mechanism(s) involved are unknown. In this study, we examine the role of cyclic
      strain in regulating bovine aortic endothelial cell (BAEC) migration and tube
      formation, indices of angiogenesis. Considering their well-documented
      mechanosensitivity, functional inter-dependence, and involvement in angiogenesis,
      we hypothesized roles for matrix metalloproteinases (MMP-2/9), RGD-dependent
      integrins, and urokinase plasminogen activator (uPA) in this process. BAECs were
      exposed to equibiaxial cyclic strain (5% strain, 1Hz for 24h) before their
      migration and tube formation was assessed by transwell migration and collagen gel
      tube formation assays, respectively. In response to strain, both migration and
      tube formation were increased by 1.83+/-0.1- and 1.84+/-0.1-fold, respectively.
      Pertussis toxin, a Gi-protein inhibitor, decreased strain-induced migration by
      45.7+/-32% and tube formation by 69.8+/-13%, whilst protein tyrosine kinase (PTK)
      inhibition with genistein had no effect. siRNA-directed attenuation of
      endothelial MMP-9 (but not MMP-2) expression/activity decreased strain-induced
      migration and tube formation by 98.6+/-41% and 40.7+/-31%, respectively. Finally,
      integrin blockade with cRGD peptide and siRNA-directed attenuation of uPA
      expression reduced strain-induced tube formation by 85.7+/-15% and 84.7+/-31%,
      respectively, whilst having no effect on migration. CONCLUSIONS: Cyclic strain
      promotes BAEC migration and tube formation in a Gi-protein-dependent PTK
      independent manner. Moreover, we demonstrate for the first time a putative role
      for MMP-9 in both strain-induced events, whilst RGD-dependent integrins and uPA
      appear only to be involved in strain-induced tube formation.

PMID- 15737625
TI  - Active oligomeric ATP synthases in mammalian mitochondria.
AB  - Recently, by analysis of mildly solubilized mitochondrial membranes new
      biochemical evidences were obtained for the occurrence of ATP synthase dimers in
      mitochondria of different eukaryotes from yeast to mammals. In the case of yeast
      even higher ATP synthase oligomers could be found. Here, we analysed by BN- and
      CN-PAGE mammalian (bovine and rat) mitochondria from five different tissues,
      which were efficiently but very mildly solubilized with digitonin. In
      mitochondria from all investigated tissues besides ATP synthase monomers (V(1))
      not only dimeric ATP synthase (V(2)) but for the first time also higher
      oligomers, at least trimers (V(3)) and tetramers (V(4)), were separated. Compared
      with BN-PAGE, by CN-PAGE analysis the yields of preserved respiratory
      supercomplexes as well as of oligomeric ATP synthases (V(2-4)) were significantly
      increased. The latter represent the majority of total ATP synthases in all cases.
      Importantly, all different ATP synthase species from the five tissues displayed
      in-gel ATP hydrolase activity, suggesting that homooligomeric ATP synthases are
      the constitutive, enzymatically competent organization of mammalian ATP synthases
      in the inner mitochondrial membrane.

PMID- 15737627
TI  - Localization of Escherichia coli poly(A) polymerase I in cellular membrane.
AB  - Poly(A) polymerase I (PAP I), the pcnB gene product, is the main enzyme
      responsible for RNA polyadenylation in Escherichia coli. Polyadenylated RNA
      molecules are rapidly degraded by a multiprotein complex called RNA degradosome.
      Here we demonstrate that apart from its presence in cytosol, PAP I is also
      localized in cellular membrane. Although this observation might appear
      surprising, it was demonstrated recently by others that E. coli RNA degradosome
      is also associated with the cytoplasmic membrane. Moreover, we show that
      development of single-stranded RNA bacteriophages MS2 and Qbeta, but not that of
      single-stranded DNA bacteriophage M13, is more efficient in the pcnB mutant
      relative to an otherwise isogenic pcnB(+) host.

PMID- 15737626
TI  - 8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down
      regulating LPS-induced activity of NF-kappaB and C/EBPbeta in Raw 264.7 cells.
AB  - In activated macrophage, large amounts of nitric oxide (NO) are generated by
      inducible nitric oxide synthase (iNOS), resulting in acute or chronic
      inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide
      (LPS) to mimic inflammation, 8-hydroxyquinoline (8HQ) inhibited the LPS-induced
      expression of both iNOS protein and mRNA in a parallel dose-dependent manner. 8HQ
      did not enhance the degradation of iNOS mRNA. To investigate the mechanism by
      which 8HQ inhibits iNOS gene expression, we examined the activation of MAP
      kinases in Raw 264.7 cells. We did not observe any significant change in the
      phosphorylation of MAPKs between LPS alone and LPS plus 8HQ-treated cells.
      Moreover, 8HQ significantly inhibited the DNA-binding activity of nuclear factor
      kappaB (NF-kappaB) and CCAAT/enhancer-binding protein beta (C/EBPbeta), but not
      activator protein-1 and cAMP response element-binding protein. Taken together,
      these results suggest that 8HQ acts to inhibit inflammation through inhibition of
      NO production and iNOS expression through blockade of C/EBPbeta DNA-binding
      activity and NF-kappaB activation.

PMID- 15737628
TI  - Characterization of BIV Env core: implication for mechanism of BIV-mediated cell
      fusion.
AB  - Entry of lentiviruses, such as human immunodeficiency virus type 1 (HIV-1) and
      simian immunodeficiency virus (SIV), requires folding of two heptad repeat
      regions (HR1 and HR2) of gp41 into a trimer-of-hairpins, which subsequently
      brings virus and cell membrane into fusion. This motif is a generalized feature
      of viral fusion proteins and has been exploited in generating antiviral fusion
      agents. In the present paper, we report structural characters of Env protein from
      another lentivirus, bovine immunodeficiency virus (BIV), which contributes to a
      good animal model of HIV. BIV HR1 and HR2 regions are predicted by two different
      programs and expressed separately or conjointly in Escherichia coli. Biochemical
      and biophysical analyses show that the predicted HRs of BIV Env can form a stable
      trimer-of-hairpins or six-helix bundle just like that formed by feline
      immunodeficiency virus Env. Cell fusion assay demonstrates that the HR2 peptide
      of BIV can efficiently inhibit the virus-mediated cell fusion.

PMID- 15737629
TI  - p38 MAPK-dependent and YY1-mediated chemokine receptors CCR5 and CXCR4 up
      regulation in U937 cell line infected by Mycobacterium tuberculosis or
      Actinobacillus actinomycetemcomitans.
AB  - We have found previously that the chemokine receptors CCR5 and CXCR4, which are
      the coreceptors of HIV, are up-regulated in human macrophage cell line U937
      infected by Mycobacterium tuberculosis (MTB). This suggests another possibility
      to explain the co-infection of MTB and HIV. In order to detect the up-regulation
      of CCR5 and CXCR4 as a unique phenomenon of MTB infection or a ubiquitous
      phenomenon of pathogenic bacteria, we investigated the expression changes of
      these two chemokine receptors in macrophages attacked by another bacterium
      Actinobacillus actinomycetemcomitans (AA) (from mRNA level and protein level). To
      reveal the molecular mechanism of these expression changes, p38 MAPK special
      inhibitor SB203580 was used and the expression of CCR5 and CXCR4 negative
      regulator YY1 transfactor was analyzed. Finally, we conclude that the up
      regulation of CCR5 and CXCR4 can at least partially contribute to the down
      regulation of transfactor YY1 which is p38 MAPK pathway-dependent and this up
      regulation has little relationship with MTB and HIV co-infection.

PMID- 15737630
TI  - Degradation of microvascular brain endothelial cell beta-catenin after co-culture
      with activated neutrophils from patients undergoing cardiac surgery with
      prolonged cardiopulmonary bypass.
AB  - The adhesion of highly activated neutrophils to cerebral microvascular
      endothelial cells (MVECs) may contribute to disruption and hyperpermeability of
      the blood-brain barrier (BBB) after cardiac surgery with prolonged
      cardiopulmonary bypass (CPB). A correlation between CPB duration and neutrophil
      mediated BBB damage has not been investigated on the cellular level yet.
      Therefore, we studied the effects of neutrophils from cardiac surgery patients
      with CPB time <80 min (group I; n=8) and >80 min (group II; n=8) on the integrity
      of cultured porcine MVEC. Ex vivo, neutrophils of group II but not of group I
      significantly degraded the zonula adherens molecule beta-catenin whereas VE
      cadherin and occludin were not modified. The transendothelial electric resistance
      as a measure for the integrity of the endothelial monolayers was reduced over
      time in both groups. In conclusion, prolonged CPB time entails neutrophil
      mediated decrease in MVEC beta-catenin expression, and thus may be an important
      trigger for BBB disruption.

PMID- 15737631
TI  - T-cadherin GPI-anchor is insufficient for apical targeting in MDCK cells.
AB  - T-cadherin is a 95kDa glycoprotein member of the cadherin family of adhesion
      molecules attached to the extracellular surface of the cell membrane through a
      glycosyl-phosphatidylinositol (GPI)-anchor. Whether a T-cadherin ectodomain
      apical targeting signal or the GPI-anchor itself targets this protein to the
      apical membrane is not known. Chimeras of the reporter EGFP and T-cadherin have
      demonstrated that a minimal construct consisting of the C-terminal 25 amino acids
      including the N690 (omega-site) of T-cadherin was sufficient to GPI-anchor the
      EGFP protein. However, efficient GPI-anchor with minimal secretion of the protein
      required an additional 5 residues (omega-1 to omega-5). The GPI-anchored chimeras
      fractionated to the Triton X-100 detergent insoluble fraction and were released
      to the cell culture supernatant by phosphoinositide-specific phospho-lipase C
      digestion. When expressed in MDCK cells, all GPI-anchored chimeras targeted to
      the basolateral membrane, while the T/N-chimera and the wild-type T-cadherin
      targeted to the apical membrane. Therefore, T-cadherin is an example of another
      rare GPI-anchored protein where the anchor itself is not sufficient for apical
      targeting in MDCK cells.

PMID- 15737632
TI  - Cloning and characterization of full length of a novel zebrafish gene Zsrg
      abundantly expressed in the germline stem cells.
AB  - Using the digital differential display program of the National Center for
      Biotechnology Information, we identified a contig of expression sequence tags
      (ESTs) (Accession No. BM316936), which came from zebrafish ovary and testis
      libraries. The full-length cDNA of this transcript was cloned and further
      confirmed by polymerase chain reaction and sequencing. The full-length cDNA of
      the novel gene is 807bp and encodes a novel protein of 187 amino acids, which
      shares no significant homology with any other known proteins. Characterization of
      genomic sequences of the gene revealed that it spans 6kb on the linkage group 3
      and is composed of five exons and four introns. RT-PCR analysis showed that it
      was expressed in mature oocytes and one-cell stage, and persisted until 24h of
      development. RT-PCR also revealed that it is expressed in gonad and kidney, with
      the highest level of expression in the testis. The expression sites of the novel
      gene in adult gonad were further localized by in situ hybridization to oogonia
      and growing oocytes in ovary and to spermatogonia, spermatocytes but not to
      spermatids in testis. Based on its abundance in testis and the germline stem cell
      spermatogonia and oogonia, we hypothesize that it may function as a testicular
      development and gametogenesis related gene that plays important roles in
      spermatogenesis, and named it Zsrg (zebrafish testis spermatogenesis related
      gene, Zsrg).

PMID- 15737633
TI  - Characterization of a RAB5 homologue in Trypanosoma cruzi.
AB  - RAB proteins are small GTPases involved in exocytic and endocytic pathways of
      eukaryotic cells, controlling vesicle docking and fusion. RABs show a remarkable
      specificity in subcellular localization, so they can be used as molecular markers
      for studying protein trafficking in Trypanosoma cruzi, the causal agent of
      Chagas' disease. RAB5 is a component of early endosomes. It has been identified
      in kinetoplastids such as Trypanosoma brucei and Leishmania donovani. In this
      work, we describe the characterization of the complete coding sequence of a RAB5
      gene homologue in T. cruzi (TcRAB5, GenBank Accession No. AY730667). It is
      present as a single copy gene, located at chromosomal bands XIII and XIV. TcRAB5
      shares the highest degrees of similarity (71%) and identity (63%) with
      Trypanosoma brucei rhodesiense RAB5a and contains all five characteristic RAB
      motifs. TcRAB5 is transcribed as a single 1.5kb mRNA in epimastigotes. Its
      transcript was also detected in the other two forms of the parasite, metacyclic
      trypomastigotes and spheromastigotes. The recombinant TcRAB5 protein was able to
      bind and hydrolyze GTP. The identification of proteins involved in T. cruzi endo-
      and exocytic pathways may generate cellular compartment markers, an invaluable
      tool to better understand the vesicular transport in this parasite.

PMID- 15737634
TI  - Sleeping Beauty-mediated down-regulation of huntingtin expression by RNA
      interference.
AB  - Huntington disease (HD) is a devastating neurologic disorder that is
      characterized by abnormal expansion of a CAG nt repeat in the first exon of the
      huntingtin (htt) gene, producing a mutant protein with an elongated polyglutamine
      stretch. The presence of this mutant protein is correlated with the
      characteristic loss of striatal neurons and the clinical manifestation of HD.
      Currently there is no effective treatment for the associated cell death. The aim
      of this study was to evaluate an innovative strategy combining RNA interference
      (RNAi) and gene transfer via the nonviral Sleeping Beauty (SB) transposon system
      to down-regulate Htt expression. siRNA expression vectors were designed to target
      exons 1, 4, 6, and 62 of the human htt gene. Real-time RT-PCR and Western blot
      analysis were used to quantify Htt mRNA and protein levels, respectively, in
      human cell lines. The results indicated that selected siRNA constructs
      significantly decreased Htt mRNA and protein levels relative to controls. In
      addition, SB transposition of the siRNA constructs into the genome reduced long
      term protein expression of Htt by approximately 90%. The combination of siRNA,
      the SB transposon, and an accurate transgenic mouse model may permit evaluation
      of this approach in preventing the pathogenesis associated with expression of
      mutant Htt.

PMID- 15737635
TI  - Transcriptional down-regulation through nuclear exclusion of EWS methylated by
      PRMT1.
AB  - The EWS gene is known to be chromosomally translocated and fused to various
      members of the DNA-binding transcription factors in Ewing's sarcoma and primitive
      neuroectodermal tumor. The product of this gene encodes the N-terminal
      transcriptional activation domain and the C-terminal RNA-binding domain
      containing an RNA-recognition motif and three arginine-glycine-glycine rich (RGG)
      motifs. Recently, we demonstrated EWS as a coactivator for hepatocyte nuclear
      factor 4 (HNF4)-mediated transcription. However, regulatory factors controlling
      EWS function are poorly characterized. In this study, we found that a protein
      arginine methyltransferase, PRMT1, physically interacts with EWS, whose cellular
      localization depends upon its RGG motifs targeted for methylation. Overexpression
      of PRMT1 down-regulates coactivator activity of EWS for HNF4-mediated
      transcription, because of the cytoplasmic retention of EWS from the nucleus.
      These results suggest that PRMT1 plays a post-translationally important role in
      regulating the transcriptional activity.

PMID- 15737636
TI  - Alpha-actinin-2, a cytoskeletal protein, binds to angiogenin.
AB  - Angiogenin is an angiogenic factor which is involved in tumorigenesis. However,
      no particular intracellular protein is known to interact directly with
      angiogenin. In the present study, we reported the identification of alpha-actinin
      2, an actin-crosslinking protein, as a potential angiogenin-interacting partner
      by yeast two-hybrid screening. This interaction was confirmed by different
      approaches. First, angiogenin was pulled down together with His-tagged alpha
      actinin-2 by Ni(2+)-agarose resins. Second, alpha-actinin-2 was
      coimmunoprecipitated with angiogenin by anti-angiogenin monoclonal antibody.
      Third, the in vivo interaction of these two proteins was revealed by fluorescence
      resonance energy transfer analysis. Since members of alpha-actinin family play
      pivotal roles in cell proliferation, migration, and invasion, the interaction
      between alpha-actinin-2 and angiogenin may underline one possible mechanism of
      angiogenin in angiogenesis. Our finding presents the first evidence of an
      interaction of a cytosolic protein with angiogenin, which might be a novel
      interference target for anti-angiogenesis and anti-tumor therapy.

PMID- 15737637
TI  - The expression of the rice (Oryza sativa L.) homologue of Snm1 is induced by DNA
      damages.
AB  - We isolated and characterized the rice homologue of the DNA repair gene Snm1
      (OsSnm1). The length of the cDNA was 1862bp; the open reading frame encoded a
      predicted product of 485 amino acid residues with a molecular mass of 53.2kDa.
      The OsSnm1 protein contained the conserved beta-lactamase domain in its internal
      region. OsSnm1 was expressed in all rice organs. The expression was induced by
      MMS, H(2)O(2), and mitomycin C, but not by UV. Transient expression of an
      OsSnm1/GFP fusion protein in onion epidermal cells revealed the localization of
      OsSnm1 to the nucleus. These results suggest that OsSnm1 is involved not only in
      the repair of DNA interstrand crosslinks, but also in various other DNA repair
      pathways.

PMID- 15737638
TI  - DARPP-32 and inhibitor-1 are expressed in pancreatic beta-cells.
AB  - Insulin secretion from pancreatic beta-cells has to be tightly regulated to
      ensure accurate glucose homeostasis. The capacity of beta-cells to respond to
      extracellular stimulation is determined by several signaling pathways. One
      important feature of these pathways is phosphorylation and subsequent
      dephosphorylation of a wide range of cellular substrates. Protein phosphatase 1
      (PP1) is a major eukaryotic serine/threonine protein phosphatase that controls a
      multitude of physiological processes. We have investigated the expression and
      cellular distribution of two endogenous inhibitors of PP1 activity in beta-cells.
      RT-PCR, Western blotting, and immunohistochemistry showed that DARPP-32 and
      inhibitor-1 are present in insulin-secreting endocrine beta-cells. Subcellular
      fractionation of mouse islets revealed that both PP1 inhibitors predominantly
      localized to cytosol-enriched fractions. Inhibitor-1 was also present in
      fractions containing plasma membrane-associated proteins. These data indicate a
      potential role for DARPP-32 and inhibitor-1 in the regulation of PP1 activity in
      pancreatic beta-cell stimulus-secretion coupling.

PMID- 15737639
TI  - Vesicle mobility studied in cultured astrocytes.
AB  - Astrocytes release many neuroactive substances, which are stored in membrane
      bound vesicles and may play a role in synapse modulation and in the coupling
      between neuronal activity and the local blood flow. However, the mobility of
      these vesicles in astrocytes has not been studied yet. We here used a
      fluorescently tagged proatrial natriuretic peptide to label single vesicles and
      dynamic microscopy to monitor their mobility. To track and analyze labeled
      vesicles, we employed a computer software. We found two modes of vesicle
      mobility, directional and non-directional. The mobility of non-directional
      vesicles is likely determined mainly by free diffusion. Only directional vesicles
      displayed a straight-line motion. The relationship of mean square displacement
      with time in directional vesicles resembled a quadratic function, indicating that
      in addition to free diffusion other mechanisms may contribute to vesicle
      movements in astrocytes, the biophysical properties of which are similar to those
      of neurons.

PMID- 15737640
TI  - Molecular analysis of the interaction between the intracellular loops of the
      human serotonin receptor type 6 (5-HT6) and the alpha subunit of GS protein.
AB  - The serotonin type 6 (5-HT(6)) receptor is a G-protein coupled receptor (GPCR)
      coupled to a stimulatory G-protein (G(S)). To identify the structural basis for
      the interaction of the 5-HT(6) receptor with the G(S) protein, we have dissected
      the interaction between GST-fusion proteins containing the second intracellular
      loop (iL2), the third intracellular loop (iL3), or the C-terminal tail of the 5
      HT(6) receptor and the alpha subunit of G(S) (Galpha(S)). The direct interaction
      of iL3 and Galpha(S) was demonstrated by co-immunoprecipitation. Furthermore, the
      kinetic parameters of the interaction between iL3 and Galpha(S) were measured by
      surface plasmon resonance, and the apparent dissociation constant was determined
      to be 0.9 x 10(-6)M. In contrast, the second intracellular loop and C-terminal
      tail regions showed negligible affinity to Galpha(S). The critical residues
      within the iL3 region for the interaction with Galpha(S) were identified as
      conserved positively charged residues near the C-terminus of iL3 by measuring the
      cellular levels of cAMP produced in response to 5-HT stimulation of cells
      transfected with 5-HT(6) receptor mutants.

PMID- 15737641
TI  - Characterisation of Tat protein transport complexes carrying inactivating
      mutations.
AB  - The Tat system functions to transport folded proteins across the bacterial
      cytoplasmic membrane and the thylakoid membrane of plant chloroplasts. Tat
      transport involves a high molecular weight TatBC-containing complex that
      transiently associates with TatA during protein translocation. Sedimentation
      equilibrium experiments were used to determine a protein-only molecular mass for
      the TatBC complex of 630+/-30kDa, suggesting that it contains approximately 13
      copies of the TatB and TatC protomers. Point mutations that inactivate Tat
      transport have previously been identified in each of TatA, TatB, and TatC.
      Analysis of the TatBC complexes formed by these inactive variants demonstrates
      that the amino acid substitutions neither affect the composition of the TatBC
      complex nor cause accumulation of the assembled TatABC translocation site. In
      addition, the TatA protein is shown not to be required for the assembly or
      stability of the TatBC complex.

PMID- 15737642
TI  - The effects of N-glycosylation sites and the N-terminal region on the biological
      function of beta1,3-N-acetylglucosaminyltransferase 2 and its secretion.
AB  - Human beta1,3-N-acetylglucosaminyltransferase 2 (beta3GnT2) is thought to be an
      enzyme that extends the polylactosamine acceptor chains, but its function and
      structure analysis are unknown. To obtain insight into the structure of
      beta3GnT2, the effects of N-glycosylation on its biological function were
      evaluated using the addition of inhibitors, site-directed mutagenesis of
      potential N-glycosylation sites, and deletion of its N-terminal region using a
      fusion protein with GFP(uv) in a baculovirus expression system. Four of five
      potential N-glycosylation sites were found to be occupied, and their biological
      function and secretion were inhibited with the treatment of N-glycosylation
      inhibitor, tunicamycin. The N-glycosylation at Asn219 was necessary for the
      beta3GnT activity; moreover, N-glycosylation at Asn127 and Asn219 was critical
      for efficient protein secretion. When Ser221 was replaced with Thr, fusion
      protein was expressed as a single band, indicating that the double band of the
      expressed fusion protein was due to the heterogeneity of the glycosylation at
      Asn219. The truncated protein consisting of amino acids 82-397 (GFP(uv)
      beta3GnT2Delta83), which lacked both one N-glycosylation site at Asn79 and the
      stem region of glycosyltransferase, was expressed as only a small form and showed
      no beta3GnT activity. These results suggest that the N-glycosylation site at
      Asn219, which is conserved throughout the beta1,3-glycosyltransferase family, is
      indispensable not only with regard to its biological function, but also to its
      secretion. The N-terminal region, which belongs to a stem region of
      glycosyltransferase, might also be important to the active protein structure.

PMID- 15737643
TI  - HIV-1 Tat modulates T-bet expression and induces Th1 type of immune response.
AB  - The HIV-1 transactivator Tat performs various viral and cellular functions.
      Primarily, it induces processive transcription from the HIV-1 LTR promoter.
      However, Tat secreted from infected cells is known to activate uninfected
      lymphocytes through receptors. To further delineate the specific target genes,
      extracellular Tat was expressed on the cell membrane of stimulator cells and co
      cultured with human PBMCs. Along with induced CD4(+) T cell proliferation and IFN
      gamma secretion, there was strong upregulation of T-bet expression which is
      majorly implicated in generating T(H)1 type of immune response. To further
      delineate the effect of extracellular Tat on HIV replication, both p24 analysis
      and in vivo GFP expression were performed. There was a significant inhibition of
      HIV-1 replication in human CEM-GFP cell line and hPBMCs. Thus, for the first time
      we report that apart from its transactivation activity, extracellular Tat acts as
      a costimulatory molecule that affects viral replication by modulating host immune
      response through induction of T-bet expression and IFN-gamma secretion.

PMID- 15737644
TI  - p73 is a p53-independent, Sp1-dependent repressor of cyclin B1 transcription.
AB  - The p53 protein family, comprised of p53, p63, and p73, has an important role in
      controlling cell growth and differentiation. We have previously reported that p53
      prevents G(2)/M transition by decreasing intracellular levels of both cyclin B1
      mRNA and protein, and attenuating the activity of the cyclin B1 promoter. The
      ability of p53 to control mitotic initiation by regulating intracellular cyclin
      B1 levels suggests that a cyclin B1-dependent G(2) checkpoint has a role in
      preventing neoplastic transformation. There is high sequence similarity between
      p73 and p53, suggesting that the two may have similar ability to repress
      transcription. In this report, we find that expression of p73alpha and p73beta
      isoforms can decrease the levels of cyclin B1 mRNA and attenuate expression from
      the cyclin B1 promoter. This attenuation occurs in both p53-deficient and p53
      containing cell lines and cannot be inhibited by a p53 variant deficient in
      repressing cyclin B1 promoter activity. p73-mediated attenuation of the cyclin B1
      promoter is dependent on the presence of functional Sp1-binding sites and is
      independent of the NF-Y-binding sites. This suggests that p73 mediates
      transcriptional repression through the Sp1 transcription factor.

PMID- 15737645
TI  - Exercise in rats does not alter hypothalamic AMP-activated protein kinase
      activity.
AB  - Recent studies have demonstrated that AMP-activated protein kinase (AMPK) in the
      hypothalamus is involved in the regulation of food intake. Because exercise is
      known to influence appetite and cause substrate depletion, it may also influence
      AMPK in the hypothalamus. Male rats that either rested or ran for 30 or 60 min on
      a treadmill (22 m/min, 10% slope) were sacrificed immediately after exercise or
      after 60 min recovery either in the fasted state or after oral gavage with
      glucose (3g/kg body weight). Exercise decreased muscle and liver glycogen
      substantially. Hypothalamic total or alpha2-associated AMPK activity and
      phosphorylation state of the AMPK substrate acetyl-CoA carboxylase were not
      changed significantly immediately following treadmill running or during fed or
      fasted recovery. Plasma ghrelin increased (P<0.05) by 40% during exercise whereas
      the concentration of PYY was unchanged. In recovery, glucose feeding increased
      plasma glucose and insulin concentrations whereas ghrelin and PYY decreased to
      (ghrelin) or below (PPY) resting levels. It is concluded that 1h of strenuous
      exercise in rats does not elicit significant changes in hypothalamic AMPK
      activity despite an increase in plasma ghrelin. Thus, changes in energy
      metabolism during or after exercise are likely not coordinated by changes in
      hypothalamic AMPK activity.

PMID- 15737646
TI  - Pioglitazone reverses down-regulation of cardiac PPARgamma expression in Zucker
      diabetic fatty rats.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a critical
      role in peripheral glucose homeostasis and energy metabolism, and inhibits
      cardiac hypertrophy in non-diabetic animal models. The functional role of
      PPARgamma in the diabetic heart, however, is not fully understood. Therefore, we
      analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake
      in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated
      with the high affinity PPARgamma agonist pioglitazone or placebo from 12 to 24
      weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well
      as lower cardiac PPARgamma, glucose transporter-4 and alpha-myosin heavy chain
      expression levels were detected in diabetic ZDF rats compared to lean animals.
      Pioglitazone increased body weight and improved metabolic control, cardiac
      PPARgamma, glut-4, and alpha-MHC expression levels in diabetic ZDF rats. Cardiac
      [(18)F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in
      untreated and pioglitazone treated ZDF fa/fa rats but was observed after
      administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARgamma
      agonists favorably affect cardiac gene expression in type-2 diabetic rats via
      activation and up-regulation of cardiac PPARgamma expression whereas improvement
      of impaired cardiac glucose uptake in advanced type-2 diabetes requires co
      administration of insulin.

PMID- 15737647
TI  - Protein disulphide isomerase binds ammodytoxin strongly: possible implications
      for toxin trafficking.
AB  - Ammodytoxin, a group IIA secreted phospholipase A(2) from the venom of the long
      nosed viper (Vipera ammodytes ammodytes), is a potent presynaptically acting
      neurotoxin. It blocks the secretion of neurotransmitter from the nerve cell, thus
      hindering the communication with the neighbouring neuron or muscle cell. To
      express the neurotoxicity, ammodytoxin should interact with specific receptors in
      the axon terminal and express phospholipase activity. Our previous results
      indicate that, following the association with a receptor on the external side of
      the presynaptic membrane, the toxin penetrates into the cytosol of the nerve
      cell. Here, we show that the toxin associates specifically with protein
      disulphide isomerase, a protein in the lumen of endoplasmic reticulum, which may
      be crucial for the retention and concentration of the toxin in this cellular
      compartment and for its subsequent transport across the membrane of endoplasmic
      reticulum into the cytosol of the nerve cell.

PMID- 15737648
TI  - Regulation of the excitatory amino acid transporter EAAT5 by the serum and
      glucocorticoid dependent kinases SGK1 and SGK3.
AB  - In the mammalian retina, glutamate re-uptake is mediated by the sodium dependent
      cotransport systems EAAT1-5 thus terminating neuronal excitation and preventing
      neuroexcitotoxicity. In retinal amacrine and ganglion cells, EAAT5 is colocalized
      with the serum and glucocorticoid inducible kinase SGK1, a serine/threonine
      kinase known to regulate transport. The study explored the possible regulation of
      EAAT5 by SGK1, its isoform SGK3, and the closely related protein kinase B. EAAT5
      was coexpressed in Xenopus laevis oocytes with or without the respective kinases.
      Transport activity was quantified by electrophysiology and cell surface
      expression was determined by chemiluminescence. Both EAAT5 mediated currents and
      EAAT5 protein abundance at the cell surface were increased by a factor of 1.5-2
      upon coexpression of SGK1 or SGK3 but not following coexpression of PKB. In
      conclusion, the kinases SGK1 and SGK3 increase EAAT5 activity by increasing cell
      surface abundance of the carrier.

PMID- 15737649
TI  - Effects of urocortin on T-type calcium currents in mouse spermatogenic cells.
AB  - Urocortin (UCN), a newly isolated peptide, has been found to play an important
      role mainly in female reproductive system. In order to investigate the effect of
      UCN on T-type calcium currents (I(Ca,T)), exploring the mechanisms of UCN's role
      in male reproductive system, especially in acrosome reaction, we directly
      measured the I(Ca,T) in mouse spermatogenic cells exposed to UCN using standard
      whole-cell patch-clamp recording technique. Our results showed that UCN
      reversibly inhibited the T-type Ca(2+) currents in the cells in a concentration
      dependent manner. The current density was inhibited by about 19% after exposure
      of the cells to UCN (0.1 microM) for 5 min, from the control value of 6.75+/-1.17
      to 5.26+/-0.82pA/pF. UCN up-shifted the current-voltage (I-V) curve. Frequency
      dependence of UCN's effects on I(Ca,T) was also observed. Moreover, UCN at 0.1
      microM did not markedly affect the activation of I(Ca,T) but shifted the
      inactivation curve of I(Ca,T) to the left. The inhibitory effect of UCN on the T
      type Ca(2+) current was not affected by Astressin, the CRF receptor blocker.
      Since T-type calcium channels are a key component in acrosome reaction, our data
      suggest that UCN might be a significant factor in male reproductive action and a
      potential contraceptive agent.

PMID- 15737650
TI  - Reverse engineering the L-type Ca2+ channel alpha1c subunit in adult cardiac
      myocytes using novel adenoviral vectors.
AB  - The alpha(1c) subunit of the cardiac L-type Ca(2+) channel, which contains the
      channel pore, voltage- and Ca(2+)-dependent gating structures, and drug binding
      sites, has been well studied in heterologous expression systems, but many aspects
      of L-type Ca(2+) channel behavior in intact cardiomyocytes remain poorly
      characterized. Here, we develop adenoviral constructs with E1, E3 and fiber gene
      deletions, to allow incorporation of full-length alpha(1c) gene cassettes into
      the adenovirus backbone. Wild-type (alpha(1c-wt)) and mutant (alpha(1c-D-))
      Ca(2+) channel adenoviruses were constructed. The alpha(1c-D-) contained four
      point substitutions at amino acid residues known to be critical for
      dihydropyridine binding. Both alpha(1c-wt) and alpha(1c-D-) expressed robustly in
      A549 cells (peak L-type Ca(2+) current (I(CaL)) at 0 mV: alpha(1c-wt) -9.94+/
      1.00pA/pF, n=9; alpha(1c-D-) -10.30pA/pF, n=12). I(CaL) carried by alpha(1c-D-)
      was markedly less sensitive to nitrendipine (IC(50) 17.1 microM) than alpha(1c
      wt) (IC(50) 88 nM); a feature exploited to discriminate between engineered and
      native currents in transduced guinea-pig myocytes. 10 microM nitrendipine blocked
      only 51+/-5% (n=9) of I(CaL) in alpha(1c-D-)-expressing myocytes, in comparison
      to 86+/-8% (n=9) of I(CaL) in control myocytes. Moreover, in 20 microM
      nitrendipine, calcium transients could still be evoked in alpha(1c-D-)-transduced
      cells, but were largely blocked in control myocytes, indicating that the
      engineered channels were coupled to sarcoplasmic reticular Ca(2+) release. These
      alpha(1c) adenoviruses provide an unprecedented tool for structure-function
      studies of cardiac excitation-contraction coupling and L-type Ca(2+) channel
      regulation in the native myocyte background.

PMID- 15737651
TI  - Identification and in silico characterization of a novel gene: TPA induced trans
      membrane protein.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a potent tumor promoter with wide
      ranging, diverse, and sometimes opposite cellular effects. Using oligonucleotide
      microarray analysis, we have identified a novel gene that is upregulated
      following treatment with TPA in the pancreatic cancer cell line CD18. Real-time
      PCR validated the microarray results in CD18 and HeLa cells, and showed that
      upregulation of the gene is time- and concentration-dependent. In silico analysis
      showed the gene product to be a single-pass transmembrane protein of 217 residues
      that is localized to the endoplasmic reticulum, thus the name TPA induced trans
      membrane protein (TTMP). A luciferase reporter assay demonstrated that
      upregulation of TTMP by TPA is triggered at the promoter level.

PMID- 15737652
TI  - RasGRP3 mediates phorbol ester-induced, protein kinase C-independent exocytosis.
AB  - Phorbol esters are involved in neurotransmitter release and hormone secretion via
      activation of protein kinase C (PKC). In addition, it has been recently reported
      to enhance neurotransmitter release in a PKC-independent manner. However, the
      exocytotic machinery is not fully clarified. Nowadays members of the RasGRP
      family are being identified as novel molecules binding to diacylglycerol and
      calcium, representing a new class of guanine nucleotide exchange factor that
      activates small GTPases including Ras and Rap1. In the present study, we
      demonstrated that RasGRP3 is expressed in endocrine tissues and mediates phorbol
      ester-induced exocytosis. Furthermore, the effects were partially blocked by PKC
      inhibitor but not mitogen-activated protein kinase kinase inhibitor, although
      both significantly suppressed the phorbol ester-induced phosphorylation of
      extracellular signal-regulated kinase 1/2. These results indicate that RasGRP3 is
      implicated in phorbol ester-induced, PKC-independent exocytosis.

PMID- 15737653
TI  - Induction of apoptosis in breast cancer cells by apomine is mediated by caspase
      and p38 mitogen activated protein kinase activation.
AB  - The 1,1-bisphosphonate ester family member apomine (SR-45023A) is known to have
      anti-tumour activity in various cancer cell types. The aims of this study were to
      determine the effect of apomine on the growth of two breast cancer cell lines,
      MCF-7 and MDA-MB-231, to ascertain whether any growth inhibitory effects found
      were due to induction of apoptosis, and to investigate the mechanism of action of
      apomine. Apomine caused significant growth inhibition of both cell lines after
      72h of treatment. Apomine-induced growth inhibition was associated with caspase
      and p38 MAPK activation and DNA fragmentation. Apomine had no effect on Ras
      localisation, nor did addition of mevalonate to treatment media prevent apomine
      induced apoptosis. We conclude that apomine induces apoptosis in breast cancer
      cells, an effect that is independent of oestrogen receptor status and is not via
      inhibition of the mevalonate pathway. Our study suggests apomine is a potential
      anti-neoplastic drug in breast cancer treatment.

PMID- 15737654
TI  - Block of inactivation-deficient cardiac Na(+) channels by acetyl-KIFMK-amide.
AB  - The Na(+) channel alpha-subunit contains an IFM motif that is critical for the
      fast inactivation process. In this study, we sought to determine whether an IFM
      containing peptide, acetyl-KIFMK-amide, blocks open cardiac Na(+) channels via
      the inner cavity. Intracellular acetyl-KIFMK-amide at 2mM elicited a rapid time
      dependent block (tau=0.24 ms) of inactivation-deficient human heart Na(+)
      channels (hNav1.5-L409C/A410W) at +50 mV. In addition, a peptide-induced tail
      current appeared conspicuously upon repolarization, suggesting that the
      activation gate cannot close until acetyl-KIFMK-amide is cleared from the open
      pore. Repetitive pulses (+50 mV for 20 ms at 1Hz) produced a substantial use
      dependent block of both peak and tail currents by approximately 65%. A F1760K
      mutation (hNav1.5-L409C/A410W/F1760K) abolished the use-dependent block by acetyl
      KIFMK-amide and hindered the time-dependent block. Competition experiments showed
      that acetyl-KIFMK-amide antagonized bupivacaine binding. These results are
      consistent with a model that two acetyl-KIFMK-amide receptors exist in proximity
      within the Na(+) channel inner cavity.

PMID- 15737655
TI  - Enhanced bone regeneration with a synthetic cell-binding peptide--in vivo
      results.
AB  - This in vivo study compared the regenerative processes within defined defects of
      the porcine skull after delivery of a porous algae-derived hydroxyapatite (adHA),
      a similar, experimental adHA carrying the cell binding peptide P-15, used solely
      and in combination with 25% autogenous bone (AB). Particulated AB served as a
      control group. During an observation period of 26 weeks, microradiography and
      histology were performed at four specific times. Significantly higher
      mineralization rates (p=0.008) were found 4 weeks after application of the
      bioactive material in combination with AB. At 12 weeks there was a significantly
      higher mineralization (p=0.036) following the application of the bioactive form
      alone. This study showed significantly higher mineralization after use of a P-15
      bioactivated material at early stages. Thus, it can be concluded that the
      application of the P-15 sequence to an hydroxyapatite accelerates the process of
      early bone formation, whereas no long-term effect was traced.

PMID- 15737656
TI  - MYBPC3 polymorphism is a modifier for expression of cardiac hypertrophy in
      patients with hypertrophic cardiomyopathy.
AB  - Clinical phenotype of hypertrophic cardiomyopathy exhibits significant inter- and
      intra-familial heterogeneities. To test if MYBPC3 polymorphism could modify the
      expression of cardiac hypertrophy, 226 patients with hypertrophic cardiomyopathy
      and 226 age- and sex-matched controls were recruited according to the diagnostic
      criteria of WHO. Genotyping was completed by using PCR, restrictive enzyme
      digestion, and sequencing. Three polymorphisms of MYBPC3 were studied, only the
      GG genotype at 18443 in exon 30 associated with thicker left ventricular wall
      (25.2+/-5.9 mm) in patient group, not the AA and AG genotypes (19.0+/-5.0mm,
      P<0.001). After multiple regression analysis for adjustment of age and sex, the
      association remained. No difference was found in the genotype distribution
      between control and patients. Our results point out that GG genotype of MYBPC3
      might be a genetic risk factor for the expression of cardiac hypertrophic
      phenotype in the patients with hypertrophic cardiomyopathy.

PMID- 15737657
TI  - Functional neuroanatomy of working memory in adults with attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) in adults is an
      increasingly recognized psychiatric disorder, linked with impairments in numerous
      life domains and with neurocognitive dysfunctions. However, the neural substrate
      of cognitive functioning in adults with this disorder has been relatively
      unexamined. The objective of this study was to examine neural functioning in ADHD
      adults during performance on a verbal working memory task. METHODS: A sample of
      unmedicated adults with ADHD (n = 20) and control subjects (n = 20) performed a 2
      back task of working memory, and the blood oxygenation level dependent (BOLD)
      functional magnetic resonance imaging (fMRI) response was used as a measure of
      neural activity during working memory performance. RESULTS: Though working memory
      performance did not differ significantly between ADHD adults and control
      subjects, ADHD adults showed significantly decreased activity in cerebellar and
      occipital regions and a trend toward decreased activation in an a priori
      predicted region of the prefrontal cortex. CONCLUSIONS: ADHD adults showed
      altered patterns of neural activity despite comparable performance on a verbal
      working memory task. These findings suggest that the cerebellum is involved in
      the pathophysiology of at least some cognitive deficits associated with ADHD and
      emphasize the need for additional research aimed at elucidating the role of the
      cerebellum in ADHD symptomatology.

PMID- 15737658
TI  - Attention-deficit/hyperactivity disorder: a preliminary diffusion tensor imaging
      study.
AB  - BACKGROUND: The purpose of this study was to explore whether there are white
      matter (WM) abnormalities in children with attention-deficit/hyperactivity
      disorder (ADHD) using diffusion tensor imaging. Based upon the literature, we
      predicted decreased fractional anisotropy (FA) findings in the frontal and
      cerebellar regions. METHODS: Eighteen patients with ADHD and 15 age- and gender
      matched healthy volunteers received DTI assessments. Fractional anisotropy maps
      of WM were compared between groups with a voxelwise analysis after intersubject
      registration to Talairach space. RESULTS: Children with ADHD had decreased FA in
      areas that have been implicated in the pathophysiology of ADHD: right premotor,
      right striatal, right cerebral peduncle, left middle cerebellar peduncle, left
      cerebellum, and left parieto-occipital areas. CONCLUSIONS: These preliminary data
      support the hypothesis that alterations in brain WM integrity in frontal and
      cerebellar regions occur in ADHD. The pattern of decreased FA might implicate the
      corticopontocerebellar circuit in the pathophysiology of ADHD.

PMID- 15737660
TI  - Differential time courses and specificity of amygdala activity in posttraumatic
      stress disorder subjects and normal control subjects.
AB  - BACKGROUND: Previous neuroimaging studies have demonstrated exaggerated amygdala
      responses to negative stimuli in posttraumatic stress disorder (PTSD). The time
      course of this amygdala response is largely unstudied and is relevant to
      questions of habituation and sensitization in PTSD exposure therapy. METHODS: We
      applied blood oxygen level dependent functional magnetic resonance imaging and
      statistical parametric mapping to study amygdala responses to trauma-related and
      nontrauma-related emotional words in sexual/physical abuse PTSD and normal
      control subjects. We examined the time course of this response by separate
      analysis of early and late epochs. RESULTS: PTSD versus normal control subjects
      have a relatively increased initial amygdala response to trauma-related negative,
      but not nontrauma-related negative, versus neutral stimuli. Patients also fail to
      show the normal patterns of sensitization and habituation to different categories
      of negative stimuli. These findings correlate with measured PTSD symptom
      severity. CONCLUSIONS: Our results demonstrate differential time courses and
      specificity of amygdala response to emotional and control stimuli in PTSD and
      normal control subjects. This has implications for pathophysiologic models of
      PTSD and treatment response. The results also extend previous neuroimaging
      studies demonstrating relatively increased amygdala response in PTSD and expand
      these results to a largely female patient population probed with emotionally
      valenced words.

PMID- 15737659
TI  - A large, double-blind, randomized clinical trial of methylphenidate in the
      treatment of adults with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The few controlled studies of methylphenidate (MPH) in adults with
      attention deficit/hyperactivity disorder (ADHD) have reported equivocal results.
      A previous, pilot study by our group suggested that these results were due to
      inadequate dosing. METHOD: We conducted a randomized, 6-week, placebo-controlled,
      parallel study of MPH in 146 adult patients with DSM-IV ADHD using standardized
      instruments for diagnosis, separate assessments of ADHD, depressive and anxiety
      symptoms, and a robust average oral daily dose of 1.1 mg/kg/day. RESULTS: We
      found a marked therapeutic response for the MPH treatment of ADHD symptoms that
      exceeded the placebo response (76% vs. 19%). Treatment was safe and well
      tolerated. Response to MPH was independent of socioeconomic status, gender, and
      lifetime history of psychiatric comorbidity. CONCLUSIONS: These results confirm
      that robust doses of MPH are effective in the treatment of adult ADHD.

PMID- 15737661
TI  - Adjunctive risperidone in the treatment of chronic combat-related posttraumatic
      stress disorder.
AB  - BACKGROUND: The efficacy and safety of risperidone was evaluated in veteran
      patients with chronic combat-related posttraumatic stress disorder (PTSD) who
      were referred to a residential treatment program. METHODS: Seventy-three subjects
      volunteered to participate in this double-blind, placebo-controlled study, which
      comprised of a 5 week residential program followed by a 3-month outpatient follow
      up. Risperidone was added to a stable psychotropic medication regimen in 92% of
      subjects. Primary outcome measures were the Clinician-Administered PTSD scale
      (CAPS-total) and its three subscales; B (Re-experiencing), C (Avoidance) and D
      (Arousal). Secondary outcome measures were the Hamilton Anxiety (HAM-A) and
      Depression (HAM-D) scales, and the Positive and Negative Syndrome Scale, Positive
      Subscale (PANSS-P). RESULTS: Sixty-five subjects were randomized and 48 completed
      the 4-month study. Significantly greater improvement in symptoms was observed in
      subjects receiving risperidone compared to placebo on the CAPS-total and CAPS-D
      subscale scores and also on HAM-A and PANSS-P. Numerically greater improvements
      in all the remaining measures were noted with risperidone, but the differences
      did not reach statistical significance. Risperidone was well tolerated.
      CONCLUSIONS: These results suggest that adjunctive risperidone improved a broad
      range of psychiatric symptoms in patients with chronic combat-related PTSD. The
      data support the concept that atypical antipsychotic medications may have a wider
      therapeutic spectrum that goes beyond the treatment of psychosis.

PMID- 15737663
TI  - Sex differences in brain activation during stress imagery in abstinent cocaine
      users: a functional magnetic resonance imaging study.
AB  - BACKGROUND: Because stress mediates drug seeking and relapse, and sex differences
      have been observed in stress and in the development of cocaine addiction, in this
      study we used functional neuroimaging to examine the effect of sex on stress
      responses in abstinent cocaine users. METHODS: In a functional magnetic resonance
      imaging session, 17 male and 10 female cocaine-dependent subjects participated in
      script-guided imagery of neutral or stress situations. Subjects rated imagery
      vividness, anxiety, and cocaine craving for each trial. Brain activation during
      the stress and neutral imagery periods relative to their own baseline was
      examined in individual subjects. Sex contrast was obtained in second-level group
      analysis. RESULTS: Female subjects demonstrated more activation, compared with
      male subjects, in left middle frontal, anterior cingulate, and inferior frontal
      cortices and insula, and right cingulate cortex during stress imagery. Region of
      interest analysis showed that the change of activity in left anterior cingulate
      and right posterior cingulate cortices both correlated inversely with the change
      of craving rating during stress imagery. CONCLUSIONS: The greater left
      frontolimbic activity in women suggests that women might use more verbal coping
      strategies than do men while experiencing stress. The results also suggest a
      distinct role of the cingulate cortices in modulating stress-induced cocaine
      craving.

PMID- 15737662
TI  - Elevated levels of endocannabinoids and CB1 receptor-mediated G-protein signaling
      in the prefrontal cortex of alcoholic suicide victims.
AB  - BACKGROUND: Alcoholism is often comorbid with mood disorders and suicide. We
      recently reported an upregulation of CB(1) receptor-mediated signaling in the
      dorsolateral prefrontal cortex (DLPFC) of subjects with major depression who died
      by suicide. In the present study, we sought to determine whether the changes in
      depressed suicides would also be present in alcoholic suicides and whether the
      endocannabinoid (EC) system plays a role in suicide in alcoholism. METHODS: The
      density of CB(1) receptor and its mediated [(35)S]GTP gamma S signaling were
      measured in the DLPFC of alcoholic suicides (AS) (n = 11) and chronic alcoholics
      (CA) (n = 11). The levels of ECs were measured by a liquid chromatograph/mass
      spectrometry. RESULTS: The CB(1) receptor density was higher in AS compared with
      the CA group in the DLPFC. Western blot analysis confirmed a greater
      immunoreactivity of the CB(1) receptor in AS. The CB(1) receptor-mediated
      [(35)S]GTP gamma S binding indicated a greater signaling in AS. Higher levels of
      N-arachidonyl ethanolamide and 2-arachidonylglycerol were observed in the DLPFC
      of AS. CONCLUSIONS: The elevated levels of ECs, CB(1) receptors, and CB(1)
      receptor-mediated [(35)S]GTP gamma S binding strongly suggest a hyperactivity of
      endocannabinoidergic signaling in AS. EC system may be a novel therapeutic target
      for the treatment of suicidal behavior.

PMID- 15737664
TI  - Treatment of aggression with topiramate in male borderline patients: a double
      blind, placebo-controlled study.
AB  - BACKGROUND: Borderline personality disorder (BPD) is a complex mental disease
      associated with severe serious functional impairment, affective instability, and
      impulsive aggression. The aim of this study was to compare the efficacy of
      topiramate versus placebo in the treatment of aggression in men with borderline
      personality disorder. METHODS: We conducted an 8-week, double-blind, placebo
      controlled study of topiramate in 42 male subjects (42 of 44) meeting DSM-IV
      criteria for BPD. The Structured Clinical Interview (SCID I and II) was carried
      out. The subjects were randomly assigned to topiramate (n = 22) or placebo (n =
      20). RESULTS: Significant changes on four STAXI scales (State Anger, p < .01;
      Trait Anger, p < .05; Anger Out, p < .01; Anger Control, p < .01) were observed
      in the subjects treated with topiramate. A nonsignificant difference was found on
      the Anger In scale (p = .86). Additional significant weight loss was observed
      (difference in weight loss between the both groups was 5.0 kg, p < .01, 95%
      confidence interval = [-6.5 to 3.4]). All subjects tolerated topiramate
      relatively well. CONCLUSIONS: Topiramate appears to be an effective agent in the
      treatment of anger in men with BPD. Mild weight loss can be expected.

PMID- 15737665
TI  - Valproate corrects the schizophrenia-like epigenetic behavioral modifications
      induced by methionine in mice.
AB  - BACKGROUND: Reelin and GAD(67) expression is downregulated in cortical
      interneurons of schizophrenia (SZ) patients. This downregulation is probably
      mediated by epigenetic hypermethylation of the respective promoters caused by the
      selective increase of DNA-methyltransferase 1 in GABAergic neurons. Mice
      receiving methionine (MET) provide an epigenetic model for neuropathologies
      related to SZ. We studied whether MET-induced epigenetic reelin promoter
      hypermethylation and the associated behavioral alterations can be reduced by
      valproate in doses that inhibit histone deacetylases (HDACs). METHODS: Mice
      treated with either methionine (MET) (5.2 mmol/kg/SC/twice daily) or valproate
      (1.5 mmol/kg/SC/twice daily) or MET+ valproate combination were tested for
      prepulse inhibition of startle (PPI) and social interaction (SI). S
      adenosylmethionine, acetylated histone 3, reelin promoter methylation, and reelin
      mRNA were assayed in the frontal cortex. RESULTS: Valproate enhances acetylated
      histone 3 content, and prevents MET-induced reelin promoter hypermethylation,
      reelin mRNA downregulation, and PPI and SI deficits. Imidazenil, a positive
      allosteric modulator at GABA(A) receptors containing alpha(5) subunits but
      inactive at receptors including alpha(1) subunits, normalizes MET-induced
      behavioral changes. CONCLUSION: This MET-induced epigenetic mouse models the
      neurochemical and behavioral aspects of SZ that can be corrected by positively
      modulating the action of GABA at alpha(5)-containing GABA(A) receptors with
      imidazenil or by inhibiting HDACs with valproate, thus opening exciting new
      avenues for treatment of epigenetically modified chromatin in SZ morbidity.

PMID- 15737666
TI  - Deep brain stimulation for refractory obsessive-compulsive disorder.
AB  - BACKGROUND: Neurosurgery (anterior capsulotomy) has been beneficial to many
      patients with debilitating, refractory obsessive-compulsive disorder (OCD), but
      the irreversibility of the procedure is an important limitation to its use.
      Nondestructive, electrical stimulation (deep brain stimulation; DBS) has proven
      an effective alternative to ablative surgery for neurological indications,
      suggesting potential utility in place of capsulotomy for OCD. METHODS: The
      effects of DBS for OCD were examined in four patients in a short-term, blinded,
      on-off design and long-term, open follow-up. The patients had incapacitating
      illness, refractory to standard treatments. Hardware developed for movement
      disorder treatment was surgically implanted, with leads placed bilaterally in the
      anterior limbs of their internal capsules. Patients received stimulation in a
      randomized "on-off" sequence of four 3-week blocks. Ongoing, open stimulation was
      continued in consenting patients after the controlled trial. RESULTS: Patients
      tolerated DBS well. Dramatic benefits to mood, anxiety, and OCD symptoms were
      seen in one patient during blinded study and open, long-term follow-up. A second
      patient showed moderate benefit during open follow-up. CONCLUSIONS: It appears
      that DBS has potential value for treating refractory psychiatric disorders, but
      additional development work is needed before the procedure is utilized outside of
      carefully controlled research protocols.

PMID- 15737667
TI  - Low-dose tryptophan depletion in recovered depressed patients induces changes in
      cognitive processing without depressive symptoms.
AB  - BACKGROUND: Acute tryptophan depletion can induce a transient reappearance of
      depressive symptoms in recovered depressed patients. The neurochemical mechanism
      is thought to be impairment of brain serotonin neurotransmission, but the
      neuropsychologic mechanisms underlying the effect are unclear. METHODS: To assess
      whether low-dose tryptophan depletion can tease out the psychological mechanisms
      sensitive to substrate depletion in vulnerable subjects without inducing mood
      changes, a between-subjects randomized design was used. Recovered depressed
      patients (n = 24) and healthy volunteers (n = 24) were administered while fasting
      either a tryptophan-free or a control mixture, containing 31.2 and 33.2 g of
      amino acids, respectively. Objective and subjective ratings of mood were made
      before and 5 hours after ingestion; at the latter time point, cognitive and
      emotional processing were also assessed. RESULTS: Low-dose tryptophan depletion
      did not affect mood. Significant changes in emotional and cognitive processing
      occurred in the recovered depressed group, however, and to a lesser extent in the
      healthy volunteers. The profile of effects seen in the recovered patients
      suggested a return of the impairments seen in acute depression. CONCLUSIONS: Our
      data suggest that low-dose tryptophan depletion permits investigation of the
      cognitive correlates of acute reductions in brain serotonin in populations
      vulnerable to depression and in healthy volunteers, without causing depressive
      symptoms.

PMID- 15737668
TI  - Mitochondrial DNA 3243A>G mutation and increased expression of LARS2 gene in the
      brains of patients with bipolar disorder and schizophrenia.
AB  - BACKGROUND: Accumulating evidence suggests mitochondrial dysfunction in bipolar
      disorder. Analyses of mitochondria-related genes using DNA microarray showed
      significantly increased LARS2 (mitochondrial leucyl-tRNA synthetase) in the
      postmortem prefrontal cortices of patients with bipolar disorder provided by the
      Stanley Foundation Brain Collection. LARS2 is a nuclear gene encoding the enzyme
      catalyzing the aminoacylation of mitochondrial tRNA(Leu). A well-studied
      mitochondrial DNA point mutation, 3243A>G, in the region of tRNA(Leu (UUR)),
      related with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and
      stroke-like episodes), is known to decrease the efficiency of aminoacylation of
      tRNA(Leu (UUR)). METHODS: The steady state level of LARS2 was examined in the
      transmitochondrial cybrids carrying 3243A>G. We examined the 3243A>G mutation in
      these brains using the peptide nucleic acid-clamped polymerase chain reaction
      restriction fragment length polymorphism method. RESULTS: LARS2 was upregulated
      in the transmitochrondrial cybrids carrying 3243A>G. The 3243A>G was detected in
      the postmortem brains of two patients with bipolar disorder and one with
      schizophrenia. These patients also showed higher levels of the mutation in their
      livers and significantly higher gene expression of LARS2 compared with other
      subjects. CONCLUSIONS: These results suggest that upregulation of LARS2 is a
      hallmark of 324A>G mutation. The accumulation of 3243A>G mutation in the brain
      may have a pathophysiologic role in bipolar disorder and schizophrenia.

PMID- 15737669
TI  - Antipsychotics alter the protein expression levels of beta-catenin and GSK-3 in
      the rat medial prefrontal cortex and striatum.
AB  - BACKGROUND: It has been demonstrated that schizophrenics have altered levels
      and/or phosphorylation states of several Wnt related proteins in the brain,
      including beta-catenin and GSK-3, and may represent susceptibility loci for
      schizophrenia. The current study was conducted to assess the effects of
      antipsychotics on beta-catenin and glycogen synthase kinase-3. METHODS: Western
      blotting and immunocytochemistry were employed to investigate the effects of
      antipsychotics on beta-catenin and glycogen synthase kinase-3 following acute,
      subchronic and chronic drug administration. Specificity of the response was
      tested using additional drugs such as fluoxetine, amphetamine and valproic acid.
      RESULTS: Significant increases in the levels of beta-catenin and glycogen
      synthase kinase-3 total protein were identified following administration of
      clozapine, haloperidol or risperidone. The phosphorylation state of GSK-3 was
      also increased but phosphorylated beta-catenin levels were unaffected. Other drug
      compounds, with the exception of raclopride, had no effect on either GSK-3 or
      beta-catenin protein levels or distribution. CONCLUSIONS: Targeting of beta
      catenin and GSK-3 is a common feature of antipsychotics regardless of class and
      appears to be mediated by D(2) dopamine receptors. Therefore changes in beta
      catenin and GSK-3 may represent one of the mechanisms through which
      antipsychotics are able to exert behavioral changes.

PMID- 15737670
TI  - Effect of phenytoin on mood and declarative memory during prescription
      corticosteroid therapy.
AB  - BACKGROUND: In humans and animals, corticosteroid excess is associated with
      impairment in declarative memory and changes in hippocampal structure. In
      animals, phenytoin pretreatment blocks the effects of stress on memory and
      hippocampal histology, although no studies have examined the use of phenytoin to
      prevent corticosteroid-associated memory changes in humans. Mood changes are also
      common with corticosteroids, but few treatment data are available. This report
      examines whether phenytoin can prevent mood or declarative memory changes
      secondary to bursts of prescription corticosteroids. METHODS: Thirty-nine
      patients with allergies or pulmonary or rheumatologic illnesses and given
      systemic corticosteroid therapy were randomized to receive either phenytoin (300
      mg/day) or placebo concurrently with the corticosteroids. Mood was assessed with
      the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and
      Activation (ACT) subscale of the Internal State Scale; declarative memory was
      assessed with the Rey Auditory Verbal Learning Test (RAVLT) at baseline and after
      approximately 7 days of corticosteroid plus phenytoin or placebo therapy.
      RESULTS: The two groups were similar in age, gender, education, and
      corticosteroid dose. The phenytoin-treated group showed significantly smaller
      increases on the ACT, a mania self-report scale, than the placebo-treated group.
      Groups did not differ significantly on RAVLT change scores. CONCLUSIONS: This is
      the first placebo-controlled study to examine whether a medication can prevent
      mood and memory changes secondary to corticosteroids. Phenytoin blocked the
      hypomanic effects of prescription corticosteroids; however, phenytoin did not
      block the declarative memory effects of corticosteroids.

PMID- 15737671
TI  - Molecular aging in human prefrontal cortex is selective and continuous throughout
      adult life.
AB  - BACKGROUND: Aging leads to morphologic and functional changes in the brain and is
      associated with increased risk for psychiatric and neurological disorders.
      METHODS: To identify age-related transcriptional changes in the human brain, we
      profiled gene expression in two prefrontal cortex (PFC) areas in postmortem
      samples from 39 subjects, ranging in age from 13 to 79 years. RESULTS: Robust
      transcriptional age-related changes were identified for at least 540 genes. Gene
      expression correlates of aging were highly specific, and the large majority of
      the 22,000 transcripts investigated were unaffected by age. Across subjects,
      changes were progressive throughout adult life and accurately predicted
      chronological age. Age-upregulated transcripts were mostly of glial origin and
      related to inflammation and cellular defenses, whereas downregulated genes
      displayed mostly neuron-enriched transcripts relating to cellular communication
      and signaling. CONCLUSIONS: Continuous changes in gene expression with increasing
      age revealed a "molecular profile" of aging in human PFC. The restricted scope of
      the transcript changes suggests cellular populations or functions that are
      selectively vulnerable during aging. Because age-related gene expression changes
      begin early in adulthood and are continuous throughout life, our results suggest
      the possibility of identifying early cellular mechanisms that may be engaged in
      preventive or detrimental age-related brain functions.

PMID- 15737672
TI  - Wheel running alters serotonin (5-HT) transporter, 5-HT1A, 5-HT1B, and alpha 1b
      adrenergic receptor mRNA in the rat raphe nuclei.
AB  - BACKGROUND: Altered serotonergic (5-HT) neurotransmission is implicated in the
      antidepressant and anxiolytic properties of physical activity. In the current
      study, we investigated whether physical activity alters factors involved in the
      regulation of central 5-HT neural activity. METHODS: In situ hybridization was
      used to quantify levels of 5-HT transporter (5-HTT), 5-HT(1A), 5-HT(1B), and
      alpha(1b)-adrenergic receptor (alpha(1b) ADR) messenger ribonucleic acids (mRNAs)
      in the dorsal (DRN) and median raphe (MR) nuclei of male Fischer rats after
      either sedentary housing or 3 days, 3 weeks, or 6 weeks of wheel running.
      RESULTS: Wheel running produced a rapid and lasting reduction of 5-HT(1B) mRNA in
      the ventral DRN. Three weeks of wheel running decreased 5-HTT mRNA in the DRN and
      MR and increased alpha(1b) ADR mRNA in the DRN. After 6 weeks of wheel running, 5
      HTT mRNA remained reduced, but alpha(1b) ADR mRNA returned to sedentary levels.
      Serotonin(1A) mRNA was increased in the MR and certain DRN subregions after 6
      weeks only. CONCLUSIONS: Data suggest that the central 5-HT system is sensitive
      to wheel running in a time-dependent manner. The observed changes in mRNA
      regulation in a subset of raphe nuclei might contribute to the stress resistance
      produced by wheel running and the antidepressant and anxiolytic effects of
      physical activity.

PMID- 15737674
TI  - Genetic contributions to the risk assessment of microcystin in the environment.
AB  - Of the known toxins produced by cyanobacteria, microcystins and nodularins are
      the most significant threat to human and animal health. Knock-out studies have
      confirmed that microcystins are produced nonribosomally by a multienzyme complex
      consisting of peptide synthetases, polyketide synthases, and tailoring enzymes.
      Gene clusters for microcystin biosynthesis have been identified and sequenced in
      the distantly related cyanobacterial genera Microcystis, Planktothrix, and
      Anabaena. Homologous genes have been detected in a nodularin-producing Nodularia
      strain. Subsequently, microcystin biosynthesis (mcy) genes have been used to
      establish molecular techniques for the detection of toxigenic cyanobacteria in
      laboratory and field studies. mcy genes of unknown origin can be assigned to the
      producing species. Techniques are currently being developed for the
      quantification of mcy genes in field populations. These initial genetic
      investigations pave the way for a molecular monitoring of microcystin- and
      nodularin-producing cyanobacteria and for studying the dynamics of toxic
      cyanobacteria in lakes. Furthermore, microcystin-deficient mutants have
      significantly increased our knowledge about the impact of the toxins on
      Microcystis-Daphnia interactions. The experience gained on microcystin
      biosynthesis genes will be valuable for a risk assessment of microcystin in the
      environment and for future water management and lake-restoration strategies.

PMID- 15737675
TI  - Ecotoxicological effects of selected cyanobacterial secondary metabolites: a
      short review.
AB  - Cyanobacteria are one of the most diverse groups of gram-negative photosynthetic
      prokaryotes. Many of them are able to produce a wide range of toxic secondary
      metabolites. These cyanobacterial toxins can be classified in five different
      groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins
      (lipopolysaccharides). Cyanobacterial blooms are hazardous due to this production
      of secondary metabolites and endotoxins, which could be toxic to animals and
      plants. Many of the freshwater cyanobacterial blooms include species of the
      toxigenic genera Microcystis, Anabaena, or Plankthotrix. These compounds differ
      in mechanisms of uptake, affected organs, and molecular mode of action. In this
      review, the main focus is the aquatic environment and the effects of these toxins
      to the organisms living there. Some basic toxic mechanisms will be discussed in
      comparison to the mammalian system.

PMID- 15737676
TI  - Detection of the cyanobacterial hepatotoxins microcystins.
AB  - Concern regarding the presence of microcystins in drinking water and their
      possible contamination in food (e.g., salad vegetables, fish, shellfish) has
      resulted in the need for reliable methods for the detection and accurate
      quantification of this class of toxins. Currently, routine analysis of
      microcystins is most commonly carried out using high-performance liquid
      chromatography with photodiode array detection (HPLC-PDA), although more
      sensitive biological assays such as antibody-based ELISAs and protein phosphatase
      inhibition assays have also proven useful. However, many of these methods have
      been hindered by the availability of a wide range of purified microcystins.
      Although over 60 variants have now been reported, only a very small number are
      commercially available and calibrated standards are not yet obtainable. This has
      led to the common practice of reporting microcystin-LR equivalence regardless of
      which variant is present. The increased availability of HPLC with online mass
      spectral analysis (HPLC-MS) may facilitate more accurate detection of toxin
      variants but as several microcystins share the same molecular mass, definitive
      identification can be difficult. A further difficulty in analyzing microcystins
      is the requirement for sample processing before analysis. Solid phase extraction
      (SPE) is typically used to enrich environmental concentrations of microcystins,
      or to eliminate contaminants from complex samples such as animal and plant
      tissues. Recently, new technologies employing recombinant antibodies and
      molecularly imprinted polymers have been exploited to develop assays and
      biosensors for microcystins. These novel detection systems are highly sensitive,
      often do not require sample processing, and offer a simpler, less expensive
      alternative to analytical techniques. They have also been successfully employed
      in solid phase extraction formats for the concentration and clean up of
      environmental samples before HPLC analysis.

PMID- 15737677
TI  - Occurrence and elimination of cyanobacterial toxins in drinking water treatment
      plants.
AB  - Toxin-producing cyanobacteria (blue-green algae) are abundant in surface waters
      used as drinking water resources. The toxicity of one group of these toxins, the
      microcystins, and their presence in surface waters used for drinking water
      production has prompted the World Health Organization (WHO) to publish a
      provisional guideline value of 1.0 mug microcystin (MC)-LR/l drinking water. To
      verify the efficiency of two different water treatment systems with respect to
      reduction of cyanobacterial toxins, the concentrations of MC in water samples
      from surface waters and their associated water treatment plants in Switzerland
      and Germany were investigated. Toxin concentrations in samples from drinking
      water treatment plants ranged from below 1.0 microg MC-LR equiv./l to more than
      8.0 microg/l in raw water and were distinctly below 1.0 microg/l after treatment.
      In addition, data to the worldwide occurrence of cyanobacteria in raw and final
      water of water works and the corresponding guidelines for cyanobacterial toxins
      in drinking water worldwide are summarized.

PMID- 15737678
TI  - Cyanobacteria and prawn farming in northern New South Wales, Australia--a case
      study on cyanobacteria diversity and hepatotoxin bioaccumulation.
AB  - Harmful cyanobacteria pose a hazard to aquatic ecosystems due to toxins
      (hepatotoxic microcystins, nodularins, and cylindrospermopsin) they produce. The
      microcystins and nodularins are potent toxins, which are also tumor promoters.
      The microcystins and nodularins may accumulate into aquatic organisms and be
      transferred to higher trophic levels, and eventually affect vector animals and
      consumers. Prawn farming is a rapidly growing industry in Australia. Because
      information regarding effects of cyanobacteria at prawn farms was lacking, we
      examined diversity of cyanobacteria and toxin production plus bioaccumulation
      into black tiger prawns (Penaeus monodon) under both field (northern New South
      Wales, Australia, December 2001-April 2002) and laboratory conditions. Samples
      were analyzed for hepatotoxins using enzyme-linked immunosorbent assay (ELISA)
      and high-performance liquid chromatography (HPLC). The maximum density of
      cyanobacteria (1 x 10(6) to 4 x 10(6) cells/l) was reached in April.
      Cyanobacteria encountered were Oscillatoria sp. (up to 4 x 10(6) cells/l),
      Pseudanabaena sp. (up to 1.8 x 10(6) cells/l), Microcystis sp. (up to 3.5 x 10(4)
      cells/l), and Aphanocapsa sp. (up to 2 x 10(4) cells/l). An uncommon
      cyanobacterium, Romeria sp. (up to 2.2 x 10(6) cells/l), was also observed.
      Contrasting earlier indications, toxic Nodularia spumigena was absent. Despite
      that both Oscillatoria sp. and Microcystis sp. are potentially hepatotoxic,
      hepatotoxin levels in phytoplankton samples remained low (up to 0.5-1.2 mg/kg dw;
      ELISA) in 2001-2002. ELISA was found suitable not only for phytoplankton but
      prawn tissues as well. Enzymatic pretreatment improved extractability of
      hepatotoxin from cyanobacteria (nodularin from N. spumigena as an example), but
      did not generally increase toxin recovery from prawn hepatopancreas. There were
      slightly increasing hepatotoxin concentrations in prawn hepatopancreas (from 6-20
      to 20-80 microg/kg dw; ELISA) during the study. Hepatotoxin concentrations in
      surface sediment remained low (<5 microg/kg dw; ELISA) throughout the study.
      Laboratory experiments indicated that prawn hepatopancreas, heart, and brain were
      primary organs for hepatotoxin bioaccumulation. Toxin concentration in other
      organs, including muscle, was less effective. Orally administered nodularin
      levels in hepatopancreas rapidly decreased from initial 830 to 250 microg/kg dw
      in 96 h. Similarly, concentration of microcystin-LR injected in prawns decreased
      from 130 to 30 microg/kg dw (hepatopancreas) in 2 h. These results demonstrate
      that potential risks caused by cyanobacteria in prawn farming (farmers, prawns,
      and consumers) were not substantial in 2001-2002. Although prawns may act as
      vectors for toxin transfer, they did not accumulate alerting amounts of
      hepatotoxins and were able to effectively detoxify them. Because bloom toxicity
      may vary, low-frequency toxin monitoring is recommended.

PMID- 15737679
TI  - Organic anion transporting polypeptides expressed in liver and brain mediate
      uptake of microcystin.
AB  - Microcystins are toxins produced by freshwater cyanobacteria. They are cyclic
      heptapeptides that exhibit hepato- and neurotoxicity. However, the transport
      systems that mediate uptake of microcystins into hepatocytes and across the blood
      brain barrier have not yet been identified. Using the Xenopus laevis oocyte
      expression system we tested whether members of the organic anion transporting
      polypeptide superfamily (rodent: Oatps; human: OATPs) are involved in transport
      of the most common microcystin variant microcystin-LR by measuring uptake of a
      radiolabeled derivative dihydromicrocystin-LR. Among the tested Oatps/OATPs, rat
      Oatp1b2, human OATP1B1, human OATP1B3, and human OATP1A2 transported microcystin
      LR 2- to 5-fold above water-injected control oocytes. This microcystin-LR
      transport was inhibited by co-incubation with the known Oatp/OATP substrates
      taurocholate (TC) and bromosulfophthalein (BSP). Microcystin-LR transport
      mediated by the human OATPs was further characterized and showed saturability
      with increasing microcystin-LR concentrations. The apparent K(m) values amounted
      to 7 +/- 3 microM for OATP1B1, 9 +/- 3 microM for OATP1B3, and 20 +/- 8 microM
      for OATP1A2. No microcystin-LR transport was observed in oocytes expressing
      Oatp1a1, Oatp1a4, and OATP2B1. These results may explain some of the observed
      organ-specific toxicity of microcystin-LR. Oatp1b2, OATP1B1, and OATP1B3 are
      responsible for microcystin transport into hepatocytes, whereas OATP1A2 mediates
      microcystin-LR transport across the blood-brain barrier.

PMID- 15737680
TI  - Cyanobacterial toxins: risk management for health protection.
AB  - This paper reviews the occurrence and properties of cyanobacterial toxins, with
      reference to the recognition and management of the human health risks which they
      may present. Mass populations of toxin-producing cyanobacteria in natural and
      controlled waterbodies include blooms and scums of planktonic species, and mats
      and biofilms of benthic species. Toxic cyanobacterial populations have been
      reported in freshwaters in over 45 countries, and in numerous brackish, coastal,
      and marine environments. The principal toxigenic genera are listed. Known sources
      of the families of cyanobacterial toxins (hepato-, neuro-, and cytotoxins,
      irritants, and gastrointestinal toxins) are briefly discussed. Key procedures in
      the risk management of cyanobacterial toxins and cells are reviewed, including
      derivations (where sufficient data are available) of tolerable daily intakes
      (TDIs) and guideline values (GVs) with reference to the toxins in drinking water,
      and guideline levels for toxigenic cyanobacteria in bathing waters. Uncertainties
      and some gaps in knowledge are also discussed, including the importance of
      exposure media (animal and plant foods), in addition to potable and recreational
      waters. Finally, we present an outline of steps to develop and implement risk
      management strategies for cyanobacterial cells and toxins in waterbodies, with
      recent applications and the integration of Hazard Assessment Critical Control
      Point (HACCP) principles.

PMID- 15737681
TI  - Guidance values for microcystins in water and cyanobacterial supplement products
      (blue-green algal supplements): a reasonable or misguided approach?
AB  - This article reviews current scientific knowledge on the toxicity and
      carcinogenicity of microcystins and compares this to the guidance values proposed
      for microcystins in water by the World Health Organization, and for blue-green
      algal food supplements by the Oregon State Department of Health. The basis of the
      risk assessment underlying these guidance values is viewed as being critical due
      to overt deficiencies in the data used for its generation: (i) use of one
      microcystin congener only (microcystin-LR), while the other presently known
      nearly 80 congeners are largely disregarded, (ii) new knowledge regarding
      potential neuro and renal toxicity of microcystins in humans and (iii) the
      inadequacies of assessing realistic microcystin exposures in humans and
      especially in children via blue-green algal food supplements. In reiterating the
      state-of-the-art toxicology database on microcystins and in the light of new data
      on the high degree of toxin contamination of algal food supplements, this review
      clearly demonstrates the need for improved kinetic data of microcystins in humans
      and for discussion concerning uncertainty factors, which may result in a lowering
      of the present guidance values and an increased routine control of water bodies
      and food supplements for toxin contamination. Similar to the approach taken
      previously by authorities for dioxin or PCB risk assessment, the use of a toxin
      equivalent approach to the risk assessment of microcystins is proposed.

PMID- 15737682
TI  - Histone metabolic pathways and chromatin assembly factors as proliferation
      markers.
AB  - The structural organization of DNA into chromatin is of key importance to
      regulate genome function and stability. Maintenance of such an organization is
      thus crucial to preserve cellular identity. At each cell cycle, during S phase,
      this is achieved by duplication of chromatin structure in tight coordination with
      DNA replication. Such a coordinate process requires histone synthesis and their
      deposition onto DNA by chromatin assembly factors to be efficiently coupled to
      DNA synthesis. In this review, we highlight the intimate relationship between
      these chromatin-related events and DNA replication and we show how it is possible
      to take advantage of this coupling in order to identify cells with high
      replicative potential such as tumor cells. On the basis of recent data, we
      discuss the potential use of chromatin-associated factors as new proliferation
      markers of interest for cancer diagnosis and prognosis.

PMID- 15737683
TI  - Saussurea lappa induces G2-growth arrest and apoptosis in AGS gastric cancer
      cells.
AB  - The molecular effects of Saussurea lappa extracts, a traditional medicine in
      Eastern Asia, on the fate of gastric carcinoma have not been understood. In this
      study, its cytostatic effects were examined using gastric AGS cancer cells. Its
      treatment resulted in apoptosis and G2-arrest in a dose- and time-dependent
      manner. The effects were attributed to the regulation of cyclins and pro
      apoptotic molecules and suppression of anti-apoptotic molecules. Therefore, these
      results suggest that extracts of S. lappa root may be a candidate to deal with
      gastric cancers either by traditional herbal therapy or by combinational therapy
      with conventional chemotherapy.

PMID- 15737684
TI  - Selective induction of apoptosis in murine skin carcinoma cells (CH72) by an
      ethanol extract of Lentinula edodes.
AB  - The effects of ethanol extracts from four species of mushroom fruiting bodies,
      mushroom spores and mushroom cultured broth, were assessed for modulation of cell
      proliferation and apoptosis in murine skin carcinoma cells (CH72) and non
      tumorigenic epidermal cells (C50). While extracts from mycelia of Grifola
      frondosa, Ganoderma lucidum, Hericium erinaceus, or from spores of G. lucidum
      exerted little, if any, effect on proliferation, the ethanol-soluble extract of
      Lentinula edodes (L. edodes) significantly decreased cell proliferation of CH72
      cells. There were no changes in the proliferative response of the non-tumorigenic
      keratinocyte cell line, C50, to any of the mushroom extracts tested. To analyze
      cell proliferation and apoptosis, fluorescent DNA-microscopy with ethidium
      bromide and acridine orange staining of cells revealed L. edodes reduced cell
      proliferation and induced apoptosis in time- and dose-dependent manners in
      carcinoma cells but had no effect in non-tumorigenic cells (C50). Cell cycle
      analysis demonstrated that L. edodes extract induced a transient G(1) arrest,
      with no changes observed in the non-tumorigenic cells (C50).

PMID- 15737685
TI  - Antimutagenicity of selenium-enriched rice on mice exposure to cyclophosphamide
      and mitomycin C.
AB  - The in vivo antimutagenicity of Se-enriched rice was evaluated by bone marrow
      micronucleus and testicle chromosomal aberrations assay in mice exposed to
      cyclophosphamide (CP) and mitomycin C (MMC). Regular rice did not alter the
      occurrence of chemical-induced mutation. However, the addition of Se-enriched
      rice or selenite significantly inhibited the incidence of CP-induced micronuclei
      and MMC-induced chromosomal aberration in mice and the effect was dose-dependent.
      Providing selenite or Se-enriched rice also significantly increased the activity
      of glutathione peroxidase in liver and the selenium concentration in blood
      compared to regular rice. No significant differences were found in mice body
      weight gain. These results revealed the antimutagenic potential of Se-enriched
      rice against chemical-induced mutation.

PMID- 15737686
TI  - Structure-activity relationships of quassinoids for eukaryotic protein synthesis.
AB  - The effect of 63 quassinoids on eukaryotic protein synthesis has been
      investigated. Seventeen of the tested compounds showed potent in vitro activity,
      with IC50s below 2 microM for inhibition in Krebs ascites translation extracts.
      Sixteen of these quassinoids were also potent inhibitors of in vivo protein
      synthesis when exposed to Hela cells for 1 h. Our results led to the following
      structure-activity relationships for quassinoids regarding translation
      inhibition. Activity is influenced by (i) the nature of the C-15 side chain, (ii)
      the nature of A ring modifications, (iii) the presence or absence of a sugar
      moiety, and (iv) the presence of an epoxymethano bridge.

PMID- 15737687
TI  - The combination of Jun N-terminal kinase inhibitor and TNP-470 blocks
      carcinosarcoma-induced endothelial cell tube formation in a synergistic manner.
AB  - We assessed the usefulness of Jun N-terminal kinase inhibitor (JNK-I) as an anti
      angiogenic agent against a human uterine carcinosarcoma cell line (FU-MMT-1). JNK
      I blocked FU-MMT-1-induced human arterial endothelial cell (HAEC) tube formation
      in an in vitro co-culture model. Cell proliferation of FU-MMT-1 or HAEC was
      inhibited by JNK-I. In addition, JNK-I blocked matrix metalloproteinase
      production but not vascular endothelial growth factor (VEGF) secretion in HAECs.
      Although low concentrations of JNK-I or TNP-470, an anti-cancer agent, did not
      separately block FU-MMT-1-induced tube formation, such tube formation was blocked
      by the combination of low concentrations of JNK-I and TNP-470 because TNP-470
      blocked VEGF production, suggesting that JNK-I and TNP-470 had a synergistic
      effect and might be effective in patients with carcinosarcoma.

PMID- 15737688
TI  - Estradiol-induced ezrin overexpression in ovarian cancer: a new signaling domain
      for estrogen.
AB  - We have for the first time exposed estrogen's role in the epithelial ovarian
      cancer (OVCA) metastatic cascade and discovered that it is related to the
      induction of ezrin over-expression. 17beta Estradiol (E2) was administered to
      SKOV3 (ERalpha>beta) and DOV13 (ERalpha<ERbeta) OVCA cells in serum-and phenol
      red-free medium fortified with transferrin and insulin. Incubated cells that
      penetrated Matrigel membranes were counted, immunostained and analyzed for
      immunoreactive ezrin. E2 induced an invasive phenotype with translocation of
      ezrin to cell edges, including pseudopodia and ruffles. A strong correlation was
      found between ezrin expression and Matrigel penetration induced by E2. Increases
      in cell number and ezrin expression were confirmed by flask incubations. E2
      stimulation of OVCA cell proliferation, motility and Matrigel penetration was
      dose-related and raloxifene or tamoxifen blocked E2's effect, supporting an ER
      action. This previously unreported effect of estrogen on ezrin expression may
      play a role in the clinical course of estrogen-sensitive cancers and other normal
      or diseased cell actions.

PMID- 15737689
TI  - Differential staining of dysplastic aberrant crypt foci in the colon facilitates
      prediction of carcinogenic potentials of chemicals in rats.
AB  - We developed a novel and simple method to identify dysplastic aberrant crypt foci
      (ACF) induced in rats by colon carcinogens more efficiently and selectively
      without conducting laborious histological examination, which usually requires
      enough time to get final diagnosis. By adding a simple decolorization process
      with 70% methanol after conventional 0.2% methylene blue staining, dysplastic ACF
      could be differentially contrasted. To examine the validity of this novel method,
      which we refer to as differential staining, we analyzed colonic lesions induced
      by three heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine, and found that the number of dysplastic ACF detected more precisely
      reflected their carcinogenic potential than the total numbers of ACF.

PMID- 15737690
TI  - Neoxanthin and fucoxanthin induce apoptosis in PC-3 human prostate cancer cells.
AB  - Neoxanthin and fucoxanthin, which have the characteristic structure of 5,6
      monoepoxide and an allenic bond, were previously found to reduce the viability of
      human prostate cancer cells most intensively among 15 dietary carotenoids tested.
      In the present study, the induction of apoptosis in PC-3 cells by these two
      carotenoids was characterized by morphological changes, DNA fragmentation, an
      increased percentage of hypodiploid cells, and cleavages of caspase-3 and PARP.
      The ratio of apoptotic cells reached more than 30% after treatment for 48 h with
      20 microM carotenoids. They reduced the expression of Bax and Bcl-2 proteins, but
      not Bcl-X(L). Fucoxanthin accumulated in the cells at the same level as
      neoxanthin. Moreover, fucoxanthinol, a deacetylated product of fucoxanthin,
      formed in the cells treated with fucoxanthin and reached a level comparable to
      that of fucoxanthin after incubation for 24 h. Treatment by fucoxanthinol alone
      also induced apoptosis in PC-3 cells. Thus, neoxanthin and fucoxanthin treatments
      were found to induce apoptosis through caspase-3 activation in PC-3 human
      prostate cancer cells.

PMID- 15737691
TI  - Hypersensitivity in DNA mismatch repair-deficient colon carcinoma cells to DNA
      polymerase reaction inhibitors.
AB  - We studied the cytotoxic effects of various DNA replication inhibitors on MMR
      deficient and -proficient colon carcinoma cell lines. DNA polymerase (pol)
      inhibitors including aphidicolin and gemcitabine, and hydroxyurea were more toxic
      (1.7 to 2.8-fold) to hMLH1-deficient HCT116 than to hMLH1-proficient HCT116+ch3.
      Similarly, pol inhibitors were more toxic to hMSH2-deficient LoVo than to hMSH2
      proficient LoVo+ch2. In contrast, DNA topoisomerase I inhibitors, such as CPT-11,
      SN-38, and topotecan, were more toxic to MMR-proficient cells. Our results
      suggest that MMR-deficient colon carcinoma cells are hypersensitive to inhibitors
      of the pol reaction.

PMID- 15737692
TI  - Transforming growth factor-beta1 induces LMO7 while enhancing the invasiveness of
      rat ascites hepatoma cells.
AB  - We have previously shown that transforming growth factor-beta1 (TGF-beta1)
      markedly stimulates the invasive capacity of rat ascites hepatoma AH130 W1 cells
      in vitro and in vivo. A differential hybridization procedure was used to isolate
      genes that were specifically up-regulated in TGF-beta1 treated W1 cells. Among
      ten independent cDNA clones, we focused on LMO7 and a variant isoform, LMO7S,
      that was generated by alternative splicing. LMO7 had PDZ and LIM domains, while
      LMO7S had only PDZ domain. TGF-beta1 up-regulated expression levels of LMO7 and
      LMO7S. LMO7 expression was up-regulated in the highly metastatic clone MM1.

PMID- 15737693
TI  - Frequent mutation related with overexpression of DNA polymerase beta in primary
      tumors and precancerous lesions of human stomach.
AB  - To explore whether DNA polymerase beta (pol beta) contributes to the malignant
      transformation of gastric mucosa, we examined pol beta in gastric tumor cell
      lines, primary tumors and precancerous lesions. Point mutations of pol beta were
      detected in 6 of 13 cell lines and 23 of 104 tissues including 35.0% (14/40) of
      gastric cancer (GC), 30.0% (3/10) of dysplasia (Dys), 28.6% (4/14) of intestinal
      metaplasia (IM) and 10.5% (2/19) of chronic atrophic gastritis (CAG),
      respectively. A frequent mutation was a T to C transition at nucleotide 889,
      which was observed in 4 GC cell lines, 7 GC, 2 Dys, and 2 IM. The level of pol
      beta expression in tumors was higher than that of their matched normal tissues
      and gradual changes from GC, Dys, CAG to IM. These results indicate that the
      mutation and overexpression of pol beta may influence the progression during
      gastric carcinogenesis.

PMID- 15737694
TI  - Chibby, a novel antagonist of the Wnt pathway, is not involved in Wilms tumor
      development.
AB  - Deregulation of the Wnt signalling pathway is a key event in the development of a
      broad spectrum of human malignancies and mutations in beta-catenin (CTNNB1), a
      central component of the Wnt pathway, have been detected in 10-15% of Wilms
      tumors (nephroblastoma). Furthermore, nuclear immunoreactivity for beta-catenin
      has been described even in the absence of detectable beta-catenin mutations. This
      suggests that other components of the Wnt pathway may be involved in the
      pathogenesis of a subgroup of Wilms tumors. Chibby (C22ORF2) is a recently
      identified antagonistic component of the Wnt pathway that inhibits the
      transcriptional activity of beta-catenin. Our study addresses the question
      whether mutation or down-regulation of Chibby is involved in Wilms tumorigenesis.
      We analysed the expression of Chibby by real time RT-PCR in 142 Wilms tumors, but
      there was no significant expression difference in any group of tumors stratified
      according to clinical, histological and mutational criteria. Mutation analysis of
      a smaller cohort did not reveal any mutations of the coding sequence. We only
      detected a constitutive splice variant leading to the absence of exon 4 in all
      Wilms tumors as well as in normal tissues. In addition, we detected a frequent
      silent polymorphism in the Chibby exon 4 sequence (435T/C). These data strongly
      suggest that despite its attractive function as a modulator of beta-catenin
      activity, Chibby is not involved in Wilms tumorigenesis.

PMID- 15737695
TI  - From eponyms to acronyms.

PMID- 15737696
TI  - Aicardi syndrome.
AB  - Aicardi syndrome (AS) is characterized by a triad of callosal agenesis, infantile
      spasms and chorioretinal 'lacunae'. It occurs only in individuals with two X
      chromosomes and is not familial. The outcome of AS is severe, with a high early
      mortality, considerable morbidity and a generally poor developmental outcome.
      However, the spectrum of AS seems broader than previously defined with a small
      proportion of the affected girls only moderately or mildly retarded. Several
      novel and important features should be added to the classic triad. The brain
      malformation is complex with cortical migration abnormalities, often cystic
      formations and sometimes choroid plexus papillomas; the eye anomalies, often
      feature a coloboma in addition to the lacunae, and focal seizures rather than
      spasms, are common. AS has been reported in 2 boys, both with an XXY complement,
      supporting the hypothesis of an X-linked gene lethal early in pregnancy for male
      conceptuses. A locus at Xp22.3 has been suggested but has not been confirmed.
      Treatment is only symptomatic.

PMID- 15737697
TI  - Benign familial infantile seizures.
AB  - In recent years, numerous publications have reported localization-related
      epilepsy with onset during early infancy, idiopathic etiology and favourable
      outcome. In 1963, Fukuyama reported cases occurring in the first 2 years of life
      characterized by partial seizures, absence of etiologic factors and benign
      outcome. Watanabe studied the localization and semiology of seizures. Later
      Vigevano and coworkers directed attention to the presence of cases with a family
      history of convulsions with benign outcome during infancy, with autosomal
      dominant inheritance, suggesting the term 'benign infantile familial convulsions'
      (BIFC). Similar cases have been described by several authors confirming that this
      is a new syndrome. In the last ILAE proposal of Classification of Epilepsy
      Syndromes this entity is called benign familial infantile seizures. Benign
      infantile seizures are divided now into familial and non-familial forms, although
      the two forms can overlap. Genetic studies led to the identification of a marker
      on chromosome 19. This was not confirmed by later studies, and genetic
      heterogeneity was hypothesized. Recently Malacarne studying eight Italian
      families with BIFC mapped a novel locus on chromosome 2. In 1997, Szepetowski
      described the association between BIFC and a later occurrence of paroxysmal
      choreoathetosis. Following the identification of a specific marker on chromosome
      16, this entity constitutes a variant of the familial forms, called infantile
      convulsions and choreoathetosis. The age at onset, the semeiology of the seizures
      and the genetic data distinguish the benign familial infantile seizures from the
      benign familial neonatal seizures. Recent data suggested that this type of
      epilepsy would be due to a channellopathy.

PMID- 15737698
TI  - Epilepsy with myoclonic absences.
AB  - Epilepsy with myoclonic absences is characterized clinically by absences
      accompanied by marked, diffuse, rhythmical myoclonias, often associated with a
      progressive tonic contraction. The ictal EEG shows bilateral, synchronous and
      symmetrical spike and wave discharges repeated at 3 Hz (similar to that observed
      in typical absences of childhood absence epilepsy) in strict relation with
      myoclonias recorded on EMG. These seizures occur many times a day. Associated
      seizures are present in 2/3 of the cases, the most frequent association being
      GTCS in 45%. The age at onset is about 7 years. There is a male preponderance.
      The evolution is variable and seems to depend on the existence or not of GTCS.
      Classical cotherapy with valproate and ethosuximide with appropriate plasma
      levels is more efficient if myoclonic absences are non-associated with GTCS. In
      cases where GTCS are associated, there is often an unfavourable outcome, with
      persistence of myoclonic absences or with modification of the epilepsy with a
      possible evolution towards a generalized cryptogenic or symptomatic form.

PMID- 15737699
TI  - Paroxysmal tonic upgaze of childhood--a review.
AB  - Ouvrier and Billson (1988) were apparently the first to describe this entity. In
      the four original cases, the clinical features were as follows: (1) onset usually
      under 1 year of age, (2) episodes of variably sustained conjugate upward
      deviation of the eyes, with neck flexion (chin down) apparently compensating for
      the abnormal eye position, (3) downbeating saccades in attempted downgaze, (4)
      normal horizontal eye movements, (5) diurnal fluctuation of symptoms, (6)
      frequent relief by sleep, (7) exacerbation with febrile illnesses, (8) varying
      degrees of ataxia, (9) neurological examination usually otherwise normal, (10)
      absence of deterioration during long-term follow-up, (11) eventual improvement,
      (12) usually negative investigations, including imaging, EEG and CSF
      neurotransmitters. As of 2002, 49 cases have been reported. Aetiological factors
      have included autosomal dominant inheritance in four families, foetal exposure to
      sodium valproate in three cases, and structural lesions in five (hypomyelination
      x 2, periventricular leukomalacia, Vein of Galen malformation, pinealoma). Only a
      few cases have responded to L-dopa. The pathophysiology is still not understood.
      The outcome appears to be good in about half the cases. Ataxia, borderline
      cognitive abilities and residual minor oculomotor disorders are seen in the
      remainder.

PMID- 15737700
TI  - Coeliac disease, epilepsy and cerebral calcifications.
AB  - Coeliac disease, epilepsy and cerebral calcifications (CEC) syndrome is a rare
      clinical condition. One hundred and seventy-one patients have been reported in
      the literature. Patients are mostly from Italy, Spain, and Argentina, suggesting
      a geographically restricted condition. Epilepsy is more frequently characterized
      by occipital seizures. It may be benign or drug-resistant, sometime evolving into
      severe epileptic encephalopathy. Gluten free diet (GFD) efficacy seems to be
      inversely related to the duration of epilepsy and the young age of the patient.
      Patients with cerebral calcifications (CC) and coeliac disease (CD) without
      epilepsy are considered as having an incomplete form of CEC syndrome. Some
      patients with epilepsy and CC without CD are supposed to have a CEC syndrome with
      silent or latent CD. Whether CEC syndrome is a genetic condition, or whether
      epilepsy and/or CC are a consequence of an untreated CD is unknown yet. Since
      histopathological findings seem to be the expression of vascular calcified
      malformation, CEC syndrome may be considered a genetically determined entity,
      such as a type of Sturge-Weber-like phacomatosis. Moreover, CEC, as well as CD,
      is associated with HLA-DQ2 and HLA-DQ8 phenotype and genotype. The progressive
      growth and late occurrence of CC before beginning a GFD, the demonstration of
      anti-gliadin antibodies in the cerebro-spinal fluid and the association with HLA
      class II genes, suggest that an immune reaction originating from the jejunal
      mucosa, triggered by gliadin in gluten intolerance predisposed subjects (HLA
      phenotype) may be responsible for seizures and CC. Moreover, a long-lasting
      untreated CD folic acid deficiency may cause calcifications. Probably, CEC is
      considered a genetic, non-inherited, ethnically and geographically restricted
      syndrome associated with environmental factors.

PMID- 15737701
TI  - Aicardi-Goutieres syndrome.
AB  - Aicardi-Goutieres syndrome is a familial progressive early onset encephalopathy
      with basal ganglia calcifications, chronic CSF lymphocytosis and high level of
      interferon-alpha in CSF. Cutaneous necrotic lesions and the neuropathological
      aspect of microangiopathy and microinfarctions suggest a vascular process in
      relation to elevated interferon-alpha. A genetic defect in the regulation of its
      synthesis may be the causal factor of the disorder.

PMID- 15737702
TI  - Absence of causative mutations and presence of autism-related allele in FOXP2 in
      Japanese autistic patients.
AB  - We analyzed the FOXP2 gene, which encodes a putative transcription factor
      containing a polyglutamine tract and a forkhead DNA-binding domain, for a
      possible causative mutation in autism. FOXP2 was reported to be mutated in
      patients with a severe speech and language disorder. FOXP2 was located on
      chromosome 7q31, which is one of the loci involved in autism. Autism and specific
      language impairment share some of their clinical phenotypes. In addition, FOXP2
      was expressed abundantly in the brain. We screened all of the exons of FOXP2 for
      causative mutations in 53 Japanese autistic patients using denaturing high
      performance liquid chromatography and direct sequencing. A delCAA in exon 5
      causing one glutamine deletion in the first polyglutamine tract was detected in
      four patients and in 2 of 50 control individuals. The frequency of the TT allele
      with the G to T base change in intron 15 was significantly high in the autistic
      population. The other base changes included one silent base change (A569G) in
      exon 5 and three in introns. Our results may suggest a relationship between
      autism and the FOXP2 gene or a gene located nearby.

PMID- 15737703
TI  - Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with
      Rett syndrome: pathological mutations and polymorphisms.
AB  - A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2)
      were identified in 145 of 219 Japanese patients with typical or atypical Rett
      syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation
      of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations,
      R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with
      classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a
      nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT,
      including the preserved speech variant (PSV). Frameshift mutations due to
      nucleotide deletion or insertion were identified in 22 patients with MECP2
      mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4.
      Three patients with classical RTT had a splicing anomaly. The wide spectrum of
      phenotypic variability in patients with RTT has been considered to be correlated
      with the mutation type and location in MECP2, and X-inactivation. However, most
      patients showed a random X-inactivation pattern evaluated by an androgen receptor
      gene polymorphism in this study, suggesting that a skewed X-inactivation might
      not be a main modification factor on clinical phenotypes of RTT. In addition,
      three new missense mutations, P176R, A378V and T479M, were identified in patients
      with RTT, but also in healthy Japanese, indicating that these mutations are non
      pathogenic in Japanese. Information about rare polymorphic variations is very
      important for the molecular diagnosis of RTT, although rare polymorphic variants
      might differ among ethnic groups.

PMID- 15737704
TI  - Benign myoclonic epilepsy in infancy: neuropsychological and behavioural outcome.
AB  - Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome of idiopathic
      generalized epilepsies with onset below 3 years of age. It has been reported that
      BMEI is associated with a good prognosis, however, recently some studies suggest
      less favourable neuropsychological outcome. We report a long-term follow-up of
      seven patients with BMEI. Seizure outcome and neuropsychological, cognitive, and
      behavioural evolution were discussed for each of them. At the end of follow-up,
      86% of children showed neuropsychological and intellectual disorders: two
      children had mental retardation, three patients achieved a borderline IQ and one
      normal but low IQ. All but one displayed neuropsychological disabilities
      including fine motor skill deficits, attention deficits, and language impairment
      and learning disorders. Our clinical data and the previous reports suggest that
      the early onset of the seizures may be one of the main factors of the illness
      giving rise to a less favourable outcome. Additional interacting factors such as
      delayed start of treatment, and efficacy of the drugs may play an important role,
      too. We believe that BMEI does not exert, different from some epileptic
      encephalopathies, a quick destroying effect but may interfere with the growth of
      developing functions, which results in long-term neuropsychological disabilities.

PMID- 15737705
TI  - Clinical course and prognosis of 27 patients with childhood onset multiple
      sclerosis in Japan.
AB  - To investigate whether outcomes of childhood onset multiple sclerosis (MS) have
      changed or not, the clinical courses of childhood onset MS in 27 patients at our
      hospital and those reported by Fukuyama in 1991 were compared. The ratios of our
      patients with poor prognosis in walking and vision were decreased. Widespread use
      of high-dose corticosteroid therapy and interferon therapy may be one cause of
      the low frequency of severe sequelae in our study.

PMID- 15737706
TI  - Clinical experience with Topiramate to counteract neuroleptic induced weight gain
      in 10 individuals with autistic spectrum disorders.
AB  - Children and adolescents with autistic spectrum disorders are treated with
      neuroleptics to limit behavioral disturbances such as aggression, hyperactivity
      and self-injury. They may experience substantial weight gain when undergoing
      treatment with atypical antipsychotics actually employed. Topiramate (TPM) is an
      antiepileptic medication that is being progressively demonstrating a wider
      spectrum of action, mainly as an agent for weight control and as a mood
      stabilizer. It was administered to a group of children and adolescents with
      autistic spectrum disorders with the aim of reversing weight gain. This is an
      open study over an observation period of 18 months of 10 children and
      adolescents, eight males and two females, mean age 13 years, SD+/-3.6, range 8-19
      years with a diagnosis of autistic disorder or pervasive developmental disorder
      not otherwise specified according to DSM-IV. Starting dosage of TPM was 0.5 mg/kg
      followed by titration of 0.5 mg/kg on a weekly basis, up to 1-3 mg/kg/day as the
      maintenance dosage. Eight subjects were undergoing long-term treatment with
      risperidone, one with pimozide and one was temporarily not on antipsychotics. Six
      patients took TPM on a regular basis and four dropped out. Variable degrees of
      weight reduction were observed in four patients, two subjects showed weight
      increase. Behavioral adverse effects were observed in three patients causing
      rapid withdrawal of the medication. TPM should be used with caution in autistic
      spectrum disorders because this population has a high risk of behavioral
      disruption.

PMID- 15737707
TI  - Computerized version of the Wisconsin card sorting test in children with high
      functioning autistic disorder or attention-deficit/hyperactivity disorder.
AB  - To determine executive dysfunctions in children with autistic disorder or
      attention-deficit/hyperactivity disorder (ADHD), we investigated high-functioning
      autistic (full scale IQ score >or==70), ADHD, and control children using the
      computerized version of the Wisconsin Card Sorting Test. Data were obtained from
      17 autistic children (16 boys and 1 girl, mean age+/-SD: 12.5+/-4.3), 22 ADHD
      children (20 boys and 2 girls, mean age+/-SD 11.3+/-2.6), and 25 control children
      (13 boys and 12 girls, mean age+/-SD: 12.7+/-3.1). Performances, indicated by
      mean number of categories achieved (5.4 in autistic, 6.5 in ADHD, and 8.8 in
      control group), total errors (38.2, 38.4, and 25.6, respectively), perseverative
      errors (11.4, 13.5, and 5.7), nonperseverative errors (27.1, 25.0, and 19.9), and
      Nelson type perseverative errors (8.9, 8.4, and 2.3), were significantly poorer
      in both autistic and ADHD groups than control group (P<0.01). Comparing the
      autistic group to the ADHD group, there were no significant differences in age,
      gender, scores of full-scale intelligent quotient (IQ), verbal or performance IQ,
      number of categories achieved or errors. The ADHD group, however, showed more
      frequent Milner type perseverative errors than the autistic group (P<0.05). The
      present study suggests that some kinds of executive function are more impaired in
      children with ADHD than in those with high-functioning autism, and that Milner
      type perseverative errors is useful parameter to differentiate the executive
      dysfunctions between autistic and ADHD children.

PMID- 15737708
TI  - Pachygyria in a girl with microcephalic osteodysplastic primordial short stature
      type II.
AB  - We report a mild form of lissencephaly or a pachygyric brain in a girl with
      microcephalic osteodysplastic primordial 'dwarfism' (MOPD) type II. She was born
      with severe intrauterine growth failure. A diagnosis of MOPD type II was
      warranted by persistent postnatal growth failure, microcephaly with a Seckel-like
      facial appearance, and distinctive radiological findings, including
      overtubulation of the long bones, metaphyseal cupping of the distal femora, and
      brachyphalangy with ivory epiphyses. Brain MRI showed thickened cerebral cortices
      with few and large gyri, most prominently in the frontal and posterior temporal
      regions. The Sylvian fissures developed incompletely, and the posterior horns of
      the lateral ventricle were dilated (colpocephaly). Despite the severe imaging
      findings, she showed only mild retardation of psychomotor development. To date,
      only minor brain malformations have attracted attention in MOPD type II. Our
      experience may suggest a wider spectrum of brain anomalies in this entity.

PMID- 15737710
TI  - Alternative strategies for energy recovery from municipal solid waste Part A:
      Mass and energy balances.
AB  - This two-part paper assesses four strategies for energy recovery from municipal
      solid waste (MSW) by dedicated waste-to-energy (WTE) plants generating
      electricity through a steam cycle. The feedstock is the residue after materials
      recovery (MR), assumed to be 35% by weight of the collected MSW. In strategy 1,
      the MR residue is fed directly to a grate combustor. In strategy 2, the MR
      residue is first subjected to light mechanical treatment. In strategies 3 and 4,
      the MR residue is converted into RDF, which is combusted in a fluidized bed
      combustor. To examine the relevance of scale, we considered a small waste
      management system (WMS) serving 200,000 people and a large WMS serving 1,200,000
      people. A variation of strategy 1 shows the potential of cogeneration with
      district heating. The assessment is carried out by a Life Cycle Analysis where
      the electricity generated by the WTE plant displaces electricity generated by
      fossil fuel-fired steam plants. Part A focuses on mass and energy balances, while
      Part B focuses on emissions and costs. Results show that treating the MR residue
      ahead of the WTE plant reduces energy recovery. The largest energy savings are
      achieved by combusting the MR residue "as is" in large scale plants; with
      cogeneration, primary energy savings can reach 2.5% of total societal energy use.

PMID- 15737711
TI  - Alternative strategies for energy recovery from municipal solid waste Part B:
      Emission and cost estimates.
AB  - This two-part paper assesses four strategies for energy recovery from Municipal
      Solid Waste (MSW) by dedicated Waste-To-Energy (WTE) plants. In strategy 1, the
      residue of Material Recovery (MR) is fed directly to a grate combustor, while in
      strategy 2 the grate combustor comes downstream of light mechanical treatment. In
      strategies 3 and 4, the MR residue is converted into Refuse Derived Fuel (RDF),
      in a fluidized cumbuster bed. The results of Part A, devoted to mass and energy
      balances, clearly show that pre-treating the MR residue in order to increase the
      heating value of the feedstock fed to the WTE plant has marginal effects on the
      energy efficiency of the WTE plant. When considering the efficiency of the whole
      strategy of waste management, the energy balances show that the more thorough the
      pre-treatment, the smaller the amount of energy recovered per unit of MR residue.
      Starting from the heat/mass balances illustrated in Part A, Part B examines the
      environmental impacts and economics of the various strategies by means of a Life
      Cycle Assessment (LCA). Results show that treating the MR residues ahead of the
      WTE plant does not provide environmental or economic benefits. RDF production
      worsens almost all impact indicators because it reduces net electricity
      production and thus the displacement of power plant emissions; it also increases
      costs, because the benefits of improving the quality of the material fed to the
      WTE plant do not compensate the cost of such improvement.

PMID- 15737712
TI  - Recycling of construction and demolition waste materials: a chemical
      mineralogical appraisal.
AB  - Building activity is currently demanding remarkable amounts of inert materials
      (such as gravel and sand) that are usually provided by alluvial sediments. The EU
      directives and Italian Legislation are encouraging the re-use of construction and
      demolition waste provided by continuous urban redevelopment. The re-utilisation
      of building waste is a relatively new issue for Italy: unfortunately the
      employment of recycled inert materials is still limited to general bulk and
      drainage fills, while a more complete re-evaluation is generally hampered by the
      lack of suitable recycling plants. In this paper, chemical-mineralogical
      characterization of recycled inert materials was carried out after preliminary
      crushing and grain-size sorting. XRF and XRD analysis of the different grain-size
      classes allowed us to recognise particular granulometric classes that can be re
      utilised as first-order material in the building activity. Specifically, the
      presented chemical-mineralogical appraisal indicates that the recycled grain-size
      fraction 0.6-0.125 mm could be directly re-employed in the preparation of new
      mortar and concrete, while finer fractions could be considered as components for
      industrial processing in the preparation of cements and bricks/tiles.

PMID- 15737713
TI  - An IR study to investigate the structural relationship of lignin-like matter and
      lignosulphonates obtained from animal-vegetable wastes.
AB  - Lignin-like matter (I) from rice hull residues and humin-like matter and (II)
      from rice hull-fecal matter compost yield, upon sulphonation by SO(3), the
      lignosulphonates III and IV, respectively. The solid state IR spectra of I and II
      are analysed and interpreted based on the functional groups content values
      obtained for III and IV by solution NMR spectroscopy. IR absorbance values at
      five selected wavelengths for I and II correlate well with functional groups
      content values for III and IV according to Beer's law. It is concluded that the
      sulphonated derivatives, aside from the -SO(3)H content, reflect well the
      chemical structure of the parent materials. No side reaction of I or II with
      SO(3), other than C sulphonation, is apparent. The above correlation may be
      useful for waste management purposes.

PMID- 15737714
TI  - Simulation of a waste incineration process with flue-gas cleaning and heat
      recovery sections using Aspen Plus.
AB  - In the present paper, the modeling of a dual-purpose plant for the production of
      electrical and thermal energy from the heat treatment of solid wastes is
      presented. Particularly, the process has been modeled by using the Aspen Plus
      Shell, with the aim of performing a study about the applicability of this
      software in the simulation of a solid waste incineration process, which involves
      complex gas-solid reactions where the solids are referred to as "non
      conventional". The model is developed to analyze and quantify the expected
      benefits associated with refuse derived fuel (RDF) thermal utilization; thus
      attention is focused on the performance of the energy recovery section.

PMID- 15737715
TI  - Leaching and mechanical behaviour of concrete manufactured with recycled
      aggregates.
AB  - The reuse of debris from building demolition is of increasing public interest
      because it decreases the volume of material to be disposed to landfill. This
      research is focused on the evaluation of the possibility of reusing recycled
      aggregate from construction or demolition waste (C&D) as a substitute for natural
      aggregate in concrete production. In most applications, cement based materials
      are used for building construction due to their cost effectiveness and
      performance; however their impact on the surrounding environment should be
      monitored. The interstitial pore fluid in contact with hydrated cementitious
      materials is characterized by persistent alkaline pH values buffered by the
      presence of hydrate calcium silicate, portlandite and alkaline ions. An
      experimental plan was carried out to investigate concrete structural properties
      in relation to alkali release in aqueous solution. Results indicate that the
      presence of recycled aggregate increases the leachability of unreactive ions (Na,
      K, Cl), while for calcium the substitution resulted in a lower net leaching. In
      spite of the lower mechanical resistance (40% less), such a waste concrete may be
      suggested as more environmentally sustainable.

PMID- 15737716
TI  - Glass-ceramics obtained by the recycling of end of life cathode ray tubes
      glasses.
AB  - This work is concerned with open-loop recycling of end of life Cathode Ray Tubes
      glass (an unsolved problem when considering that in Europe almost 90% of EOL
      electronic goods is disposed of in landfills), focusing on the development of
      glass-ceramics from panel or funnel glass with dolomite and alumina, and the
      evaluation of the tendency towards crystallisation with particular attention on
      composition and thermal treatment. Glasses were melted at a temperature of about
      1500 degrees C and transformed into glass-ceramics by different thermal
      treatments (900 degrees C to approximately 1100 degrees C temperature range and
      0.5 to approximately 8h soaking time). By using the evaluation of thermal,
      mineralogical and microstructural data it has been pointed out that a good degree
      of crystallisation is reached at about 1000 degrees C and with a high proportion
      of waste glass (50-75%) if 40-45% of CaO and MgO bearer (dolomite) is introduced.
      In this way alkaline and alkaline-earth silicate and aluminosilicate mainly
      develop probably with a surface mechanism.

PMID- 15737717
TI  - Tools for evaluation of impact associated with MSW incineration: LCA and
      integrated environmental monitoring system.
AB  - The identification of significant pollutants emitted from the contamination
      source is the first step in evaluating the impact associated with anthropic
      activity. Municipal solid waste (MSW) incinerators are still generally perceived
      as great pollutant sources, in particular due to their gaseous emissions from the
      stack, which constitute the major effluent from the plant. In this work a life
      cycle assessment and an integrated environmental monitoring system were applied
      together, in order to obtain complete information about the incineration process
      and its environmental impact. The former is a proven methodology, but its
      application to waste management systems constitutes a relatively new field of
      application with a great developmental potential. The contribution of the
      incineration process to the different environmental impact categories was
      investigated, finding many avoided impacts due to energy recovery. The latter is
      an innovative approach that allows a remarkable understanding of impact due to a
      contamination source; interesting correlations were found between heavy metals
      both in gas emissions and in natural matrices in the surroundings.

PMID- 15737718
TI  - Reuse of ground waste glass as aggregate for mortars.
AB  - This work was aimed at studying the possibility of reusing waste glass from
      crushed containers and building demolition as aggregate for preparing mortars and
      concrete. At present, this kind of reuse is still not common due to the risk of
      alkali-silica reaction between the alkalis of cement and silica of the waste
      glass. This expansive reaction can cause great problems of cracking and,
      consequently, it can be extremely deleterious for the durability of mortar and
      concrete. However, data reported in the literature show that if the waste glass
      is finely ground, under 75mum, this effect does not occur and mortar durability
      is guaranteed. Therefore, in this work the possible reactivity of waste glass
      with the cement paste in mortars was verified, by varying the particle size of
      the finely ground waste glass. No reaction has been detected with particle size
      up to 100mum thus indicating the feasibility of the waste glass reuse as fine
      aggregate in mortars and concrete. In addition, waste glass seems to positively
      contribute to the mortar micro-structural properties resulting in an evident
      improvement of its mechanical performance.

PMID- 15737719
TI  - WEEE recycling: Pyrolysis of fire retardant model polymers.
AB  - Pyrolysis treatments of model polymers were made with the aim of studying the
      recycling of wastes from electronic, electric equipment containing brominated
      flame retardants. Pyrolysis of flame retarded high impact polystyrene and epoxy
      resins were made both in flow and closed systems. Products of pyrolysis were
      analysed with FT-IR spectroscopy and GC-MS and the evolution of bromine was
      followed with a bromine ion specific electrode. The effect of alkali on pyrolysis
      was also studied demonstrating, as far epoxy resin is concerned, to be effective
      on decreasing bromine content in oil and volatile products leading to the
      recovery of bromine from the residue by washing. The alkali treatment was shown
      to be less effective in styrenic polymers containing brominated flame retardants.

PMID- 15737720
TI  - Study of the organic matter evolution during municipal solid waste composting
      aimed at identifying suitable parameters for the evaluation of compost maturity.
AB  - In this work the composting process of municipal solid wastes was studied in
      order to characterize the transformations of organic matter, particularly humic
      acid (HA). A composting process, lasting three months, was monitored by chemical
      methods; the following parameters were measured: water-soluble carbon
      concentration (WSC) and humic substances content (humic and fulvic acid (FA)).
      The effects of humification on the molecular structure of humic acid (HA) were
      also evaluated by Fourier transform infrared (FT-IR) and (13)C NMR spectroscopy.
      WSC concentration rapidly increased reaching a maximum at day-14 of the
      composting process and then declined. The humic and fulvic acid content (HA and
      FA, respectively) slightly increased during the process. The FT-IR and (13)C NMR
      spectra of HA indicate a high rate of change in structure during composting. The
      groups containing aromatic and carboxylic C increased, while polysaccharides and
      other aliphatic structures degraded during composting, resulting in HA structures
      of higher aromaticity. Therefore, spectrometric measurements could provide
      information significantly correlated to conventional chemical parameters of
      compost maturity.

PMID- 15737721
TI  - Nickel and cobalt recycling from lithium-ion batteries by electrochemical
      processes.
AB  - The presence of LiCoO(2) and LiCo(x)Ni((1-x))O(2) in the cathodic material of Li
      ion and Li-polymer batteries has stimulated the recovery of Co and Ni by
      hydrometallurgical processes. In particular, the two metals were separated by SX
      method and then recovered by electrochemical (galvanostatic and potentiostatic)
      processes. The metallic Ni has been electrowon at 250 A/m(2), pH 3-3.2 and 50
      degrees C, with 87% current efficiency and 2.96 kWh/kg specific energy
      consumption. Potentiostatic electrolysis produces a very poor Ni powder in about
      1 h with current efficiency changing from 70% to 45% depending on Ni
      concentration in the electrolyte. Current efficiency of 96% and specific energy
      consumption of 2.8 kWh/kg were obtained for Co at 250 A/m(2), pH 4-4.2 and 50
      degrees C, by using a solution containing manganese and (NH(4))(2)SO(4). The Co
      powder, produced in potentiostatic conditions (-0.9 V vs. SCE, pH 4, room
      temperature) appears particularly suitable for Co recycling as cobaltite in new
      batteries.

PMID- 15737722
TI  - Characterization and leaching of NiCd and NiMH spent batteries for the recovery
      of metals.
AB  - Since NiMH and NiCd batteries are still used in the electronic devices market, a
      treatment and recycling plant has many advantages both from the environmental and
      the economic points of view. Unfortunately, there is no relationship between
      shape, size and chemical composition of spent batteries, consequently the
      characterization and the leaching method of the starting material becomes an
      important step of the overall treatment process in choosing the best conditions
      for the selective separation of the metals by hydrometallurgy. Leaching at 20
      degrees C with H(2)SO(4) 2M for about 2h seems to be a good solution in terms of
      cost and efficiency for both battery types. The hydroxide compounds can be
      readily leached while Ni present as metallic form requires more aggressive
      conditions due to kinetic constraints. In this paper, the characterization of
      NiMH and NiCd spent batteries and the results of leaching tests in different
      conditions are reported.

PMID- 15737723
TI  - Photosynthetic microbes in freezing deserts.
AB  - Polar deserts are not devoid of life despite the extreme low temperature and
      scarcity of water. Recently, patterned stone fields--caused by periglacial
      activity--have been surveyed in the Arctic and Antarctic. It was found that the
      productivity of the cyanobacteria and algae (hypoliths) that colonise the
      underside of the stones is strongly related to the pattern of the stones. The
      hypolith assemblages were in some cases as productive as lichens, bryophytes and
      plants that resided nearby.

PMID- 15737724
TI  - Histoplasma hairpins herald hopefulness.
AB  - Histoplasma capsulatum is a significant respiratory and systemic fungal pathogen.
      Although many molecular tools have been developed, the fulfillment of Koch's
      postulates to determine gene function has been hampered by obstacles to
      homologous gene targeting. Because H. capsulatum displays a considerable array of
      virulence mechanisms and has a 40-Mb genome that is currently being sequenced,
      the capability to perform high-throughput molecular manipulations would clearly
      be beneficial. Recent demonstration and application of experimental RNA
      interference (RNAi) technology promises a major contribution to advances in this
      area.

PMID- 15737725
TI  - Insertion of the bacterial type III translocon: not your average needle stick.
AB  - Bacterial type III secretion systems are thought to translocate virulence
      proteins directly from the bacterial cytoplasm into host cells through a
      continuous molecular channel. Little is known about how the apparatus itself
      interacts with membranes and whether insertion of this structure into the host
      membrane has consequences for the bacteria apart from its beneficial role in
      delivering virulence proteins. New evidence suggests that membrane insertion of
      the bacterial type III apparatus might turn on a calcium-dependent signaling
      pathway resulting in phagolysosomal fusion.

PMID- 15737726
TI  - Genomics at the genus scale.

PMID- 15737727
TI  - What's good for the host is good for the bug.
AB  - Tuberculosis, caused by Mycobacterium tuberculosis, kills approximately two
      million people each year. The infection is characterized by an inflammatory
      response culminating in the formation of a granuloma, a collection of immune
      cells that controls the infection. However, the granuloma can be the source of
      immunopathology that encourages transmission. Recent data support the idea that
      mycobacterial products can positively and negatively regulate the inflammatory
      response. Our contention is that induction of the immune response and subsequent
      granuloma formation is beneficial to the host for control of infection, and is
      also beneficial to the bacillus, as a place to hide and as a means for
      transmitting the infection to naive hosts.

PMID- 15737728
TI  - Cyclomodulins: bacterial effectors that modulate the eukaryotic cell cycle.
AB  - Microbial pathogens have developed a variety of strategies to manipulate host
      cell functions, presumably for their own benefit. We propose the term
      "cyclomodulins" to describe the growing family of bacterial toxins and effectors
      that interfere with the eukaryotic cell cycle. Inhibitory cyclomodulins, such as
      cytolethal distending toxins (CDTs) and the cycle inhibiting factor (Cif), block
      mitosis and might constitute powerful weapons for immune evasion by inhibiting
      clonal expansion of lymphocytes. Cell-cycle inhibitors might also impair
      epithelial-barrier integrity, allowing the entry of pathogenic bacteria into the
      body or prolonging their local existence by blocking the shedding of epithelia.
      Conversely, cyclomodulins that promote cellular proliferation, such as the
      cytotoxic necrotizing factor (CNF), exemplify another subversion mechanism by
      interfering with pathways of cell differentiation and development. The role of
      these cyclomodulins in bacterial virulence and carcinogenesis awaits further
      study and will delineate new perspectives in basic research and therapeutic
      applications.

PMID- 15737729
TI  - Reactive oxygen species and development in microbial eukaryotes.
AB  - Reactive oxygen species (ROS) have been regarded as inevitable harmful by
      products of aerobic metabolism. Growing evidence, however, suggests that ROS play
      important physiological roles. This raises questions about the pathways that
      different groups of organisms use to produce and sense ROS. In microbial
      eukaryotes, recent data show (i) increased ROS levels during cell
      differentiation, (ii) the existence of ROS-producing enzymes, such as NADPH
      oxidases (NOX), (iii) the involvement of NOX in developmental processes, and (iv)
      a conservation in the signal-transduction mechanisms used to detect ROS. This
      shows that manipulation of reactive species, as strategy to regulate cell
      differentiation, is ubiquitous in eukaryotes and suggests that such strategy was
      selected early in evolution.

PMID- 15737730
TI  - The worm has turned--microbial virulence modeled in Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans is emerging as a facile and economical model
      host for the study of evolutionarily conserved mechanisms of microbial
      pathogenesis and innate immunity. A rapidly growing number of human and animal
      microbial pathogens have been shown to injure and kill nematodes. In many cases,
      microbial genes known to be important for full virulence in mammalian models have
      been shown to be similarly required for maximum pathogenicity in nematodes. C.
      elegans has been used in mutation-based screening systems to identify novel
      virulence-related microbial genes and immune-related host genes, many of which
      have been validated in mammalian models of disease. C. elegans-based pathogenesis
      systems hold the potential to simultaneously explore the molecular genetic
      determinants of both pathogen virulence and host defense.

PMID- 15737731
TI  - Pathogen-induced private conversations between natural killer and dendritic
      cells.
AB  - Natural killer (NK) cells and dendritic cells (DCs) are recruited to inflammatory
      tissues in response to infection. Following priming by pathogen-derived products,
      their reciprocal interactions result in a potent activating crosstalk that
      regulates both the quality and the intensity of innate immune responses. Thus,
      pathogen-primed NK cells, in the presence of cytokines released by DCs, become
      activated. At this stage they favor DC maturation and also select the most
      suitable DCs for subsequent migration to lymph nodes and priming of T cells. In
      addition, a specialized subset of NK cells might directly participate in the
      process of T-cell priming via the release of interferon (IFN)gamma. Thus, the
      reciprocal crosstalk between NK cells and DCs that is induced by microbial
      products not only promotes rapid innate responses against pathogens but also
      favor the generation of appropriate downstream adaptive responses.

PMID- 15737732
TI  - Tyrosine phosphatase regulation of MuSK-dependent acetylcholine receptor
      clustering.
AB  - During vertebrate neuromuscular junction (NMJ) development, nerve-secreted agrin
      induces acetylcholine receptor (AChR) clustering in muscle by activating the
      muscle-specific tyrosine kinase MuSK. Recently, it has been recognized that MuSK
      activation-dependent AChR clustering occurs in embryonic muscle even in the
      absence of agrin, but how this process is regulated is poorly understood. We
      report that inhibition of tyrosine phosphatases in cultured C2 mouse myotubes
      using pervanadate enhanced MuSK auto-activation and agrin-independent AChR
      clustering. Moreover, phosphatase inhibition also enlarged the AChR clusters
      induced by agrin in these cells. Conversely, in situ activation of MuSK in
      cultured Xenopus embryonic muscle cells, either focally by anti-MuSK antibody
      coated beads or globally by agrin, stimulated downstream tyrosine phosphatases,
      which could be blocked by pervanadate treatment. Immunoscreening identified Shp2
      as a major tyrosine phosphatase in C2 myotubes and down-regulation of its
      expression by RNA interference alleviated tyrosine phosphatase suppression of
      MuSK activation. Significantly, depletion of Shp2 increased both agrin
      independent and agrin-dependent AChR clustering in myotubes. Our results suggest
      that muscle tyrosine phosphatases tightly regulate MuSK activation and signaling
      and support a novel role of Shp2 in MuSK-dependent AChR clustering.

PMID- 15737733
TI  - Context-dependent neuronal differentiation and germ layer induction of Smad4-/-
      and Cripto-/- embryonic stem cells.
AB  - Activation of transforming growth factor-beta (TGF-beta) receptors typically
      elicits mesodermal development, whereas inhibition of this pathway induces neural
      fates. In vitro differentiated mouse embryonic stem (ES) cells with deletion of
      the TGF-beta pathway-related factors Smad4 or Cripto exhibited increased numbers
      of neurons. Cripto-/- ES cells developed into neuroecto-/epidermal cell types,
      while Smad4-/- cells also displayed mesodermal differentiation. ES cell
      differentiation into catecholaminergic neurons showed that these ES cells
      retained their ability to develop into dopaminergic and serotonergic neurons with
      typical expression patterns of midbrain and hindbrain genes. In vivo,
      transplanted ES cells to the mouse striatum became small neuronal grafts, or
      large grafts with cell types from all germ layers independent of their ES cell
      genotype. This demonstrates that Smad4-/- and Cripto-/- ES cells favor a neural
      fate in vitro, but also express the mesodermal phenotype, implying that deletion
      of either Smad4 or Cripto is not sufficient to block nonneuronal tissue
      formation.

PMID- 15737734
TI  - Regulation of Wallerian degeneration and nerve growth factor withdrawal-induced
      pruning of axons of sympathetic neurons by the proteasome and the MEK/Erk
      pathway.
AB  - Treatment of transected distal axons of rat sympathetic neurons in compartmented
      cultures with MG132 (5 microM) and other inhibitors of proteasome activity,
      preserved axonal mitochondrial function, assessed by Mitotracker-Orange and MTT
      staining, for at least 24 h. MG132 similarly protected axons from undergoing
      branch elimination (pruning) in response to local NGF deprivation. Axons
      protected by MG132 displayed persistent phosphorylation of Erk1/2, and
      pharmacological inhibition of MEK activity with U0126 (50 microM) restored rapid
      axonal degeneration. Therefore, the proteasome does not appear to be necessary as
      a general effector of protein degradation during axonal degeneration. Rather, the
      proteasome functions in the regulation of signaling pathways that control axonal
      survival and degeneration. Specifically, the down-regulation of the MEK/Erk
      pathway by the proteasome plays roles in Wallerian degeneration of severed axons
      and axonal pruning in response to local NGF deprivation. Identification of the
      pathways that regulate axonal survival and degeneration will provide possible
      target sites for pharmacological treatments of neurodegenerative diseases and
      traumatic injury.

PMID- 15737735
TI  - Nonsynaptic localization of the excitatory amino acid transporter 4 in
      photoreceptors.
AB  - Excitatory amino acid transporters (EAATs) are involved in regulating
      extracellular glutamate levels at synaptic regions in the CNS. EAAT1, 2, 3, and 5
      have been found in the mammalian retina, but the presence of EAAT4 has remained
      controversial. Recently, we found a high level of EAAT4 mRNA in the human retina,
      and this observation lead us to examine whether EAAT4 was expressed in the
      mammalian retina. Immunoblotting studies showed the presence of EAAT4
      immunoreactive proteins in human and mouse retinas, corresponding to EAAT4
      monomers and dimers. Immunohistochemistry revealed that EAAT4 was localized in
      rod and cone photoreceptor outer segments in the human retina, and in the outer
      and inner segments of mouse and ground squirrel retinas. In no case was EAAT4
      found in the outer plexiform layer or in any other layer in the retina. EAAT4
      expression by photoreceptors was confirmed by immunoblotting a purified rod outer
      segment preparation, which showed the presence of a 50-kDa EAAT4-immunoreactive
      protein. In addition, the EAAT4-associated protein, GTRAP41, was found in the
      human, mouse, and squirrel retinas as well as in the rod outer segment
      preparation. Further immunocytochemical and co-immunoprecipitation experiments
      demonstrated that GTRAP41 was colocalized and interacted in vivo with EAAT4.
      Importantly, glutamate uptake and drug inhibition experiments showed that an
      EAAT4-like glutamate uptake system is present in the rod outer segments. Finally,
      we examined whether glutamate signaling mediated by EAAT4 can modulate rod outer
      segment phagocytosis by the retinal pigment epithelium. Results of the present
      study show that EAAT4 is present in the outer segments, a nonsynaptic region of
      photoreceptors, where it might provide a feedback mechanism for sensing
      extracellular glutamate or serve as an outer barrier to prevent glutamate from
      escaping from the retina.

PMID- 15737736
TI  - Activation of p38 and N-acetylcysteine-sensitive c-Jun NH2-terminal kinase
      signaling cascades is required for induction of apoptosis in Parkinson's disease
      cybrids.
AB  - Cytoplasmic hybrid cells (cybrids) are created by selective amplification of
      mitochondrial genes against constant nuclear genetic and environmental
      backgrounds. Cybrids from patients with sporadic Parkinson's disease (PD)
      recapitulate disease features such as decreased complex I activity, increased
      oxidative stress, elevated activation of NF-kappaB, and production of Lewy body
      inclusions. We examined the activation of signaling pathways and NF-kappaB in PD
      cybrids after exposure to MAPK inhibitors and/or the antioxidant N-acetylcysteine
      (NAC). Under basal replicating conditions, PD cybrids have decreased viability
      that is associated with increased DNA condensation and poly-ADP ribose polymerase
      (PARP) cleavage as well as elevated p38 and JNK activity. Pharmacological
      inhibition of oxidative stress diminished the elevated p38, JNK activity and PARP
      cleavage, and enhanced PD cybrid viability. PD mitochondrial genes expressed in
      cybrids stimulate pro-apoptotic cell signaling and biochemistry through oxidative
      stress. These results support development of antioxidative therapeutics for PD.

PMID- 15737737
TI  - mCD24 regulates proliferation of neuronal committed precursors in the
      subventricular zone.
AB  - We previously showed that deletion of the cell surface molecule mCD24 resulted in
      an increased proliferation in adult subventricular zone (SVZ). Here, we report an
      increased PSA-NCAM+/TuJ1- population in the mCD24-/- in vivo SVZ as well as in
      vitro neurospheres. Isolated in vitro, these cells were able to generate
      neurospheres. Proliferation studies, using BrdU incorporation, showed an
      increased proliferation in P7 mCD24-/- SVZ and neurospheres. Using electron
      microscopy, the same cell types were identified in the in vivo SVZ as well as in
      vitro neurospheres from the WT and mCD24-/- mice. In mixed neurospheres, formed
      with WT and EGFP/KO cells (enhanced green fluorescent protein mCD24-/-), the WT
      environment was able to control the proliferation rate of the mCD24-/- cells, but
      was unable to regulate their differentiation. We concluded that mCD24 acts cell
      nonautonomously to regulate transit-amplifying cells proliferation and/or
      differentiation.

PMID- 15737738
TI  - Regulation of neuropilin 1 by spinal cord injury in adult rats.
AB  - Using RT-PCR, in situ hybridization, Western blotting, and immunofluorescence, we
      have analyzed the expression of neuropilin 1 (Np1) in two models of spinal cord
      injury (spinal cord hemisection and dorsal column crush) and following dorsal
      root rhizotomy in adult rats. Our results show that Np1 RNA and protein are up
      regulated in the spinal cord after all these lesions but remain unaltered in the
      adjacent dorsal root ganglia. In control animals, Np1 levels in the spinal cord
      are low and appear to be localized mainly in blood vessels, motoneurons, and in
      the superficial layers of the dorsal horn. After DCC and rhizotomy, Np1 is
      expressed de novo around the injury and in the deafferentated dorsal horn,
      respectively, mainly by OX42-positive microglial cells. Both lesions affect the
      sensory projections, and interestingly a consistent increase of Np1 signal is
      additionally seen in the dorsal horn where these projections terminate.
      Unexpectedly, this increase is bilateral after unilateral rhizotomy.

PMID- 15737739
TI  - Interaction of transducin-alpha with LGN, a G-protein modulator expressed in
      photoreceptor cells.
AB  - LGN and activator of G-protein signaling 3 (AGS3) belong to the class of G
      protein modulators containing G-protein regulatory motifs (GPR proteins).
      Evidence for the functions of these molecules has only started to emerge.
      Immunostaining of mouse retina cross-sections and serial tangential sectioning of
      the retina combined with immunoblot analysis revealed that LGN is expressed in
      the inner segments of photoreceptor cells. Double immunolabeling demonstrated
      that, following light-dependent translocation from the outer segments, the alpha
      subunit of the visual G-protein transducin (Gtalpha) colocalizes with LGN in the
      basal part of the inner segments. LGN and Gtalpha coprecipitate from the retinal
      extracts, supporting the notion of the interaction between the proteins.
      Furthermore, the GPR domain of LGN potently inhibits receptor-mediated guanine
      nucleotide exchange and steady-state GTPase activity of transducin. The
      localization and interaction with Gtalpha suggest LGN roles in modulation of
      transducin translocation and other photoreceptor cell functions.

PMID- 15737740
TI  - Beta-amyloid (Abeta) causes detachment of N1E-115 neuroblastoma cells by acting
      as a scaffold for cell-associated plasminogen activation.
AB  - A major component of neuritic plaques in brain tissue of Alzheimer's disease
      patients is the beta-amyloid peptide (Abeta). Accumulation of Abeta has been
      associated with increased neuronal cell death and cognitive decline. We have
      previously shown that amyloid peptides like Abeta bind tissue-type plasminogen
      activator (tPA) and stimulate plasmin production. Here we investigated how Abeta
      regulates plasmin formation by N1E-115 neuroblastoma cells and the effects of
      Abeta-mediated plasmin formation on cell attachment and cell survival. We find
      that Abeta induces excessive cell-associated plasmin generation that causes cell
      detachment. Cell detachment is inhibited by carboxypeptidase B (CPB), an enzyme
      that blocks plasmin formation by cleaving off C-terminal lysine residues. Plasmin
      and CPB control Abeta-induced cell detachment independently of direct effects on
      cell viability. Abeta40 as well as oligomeric and fibrillar forms of Abeta42
      stimulated tPA-mediated plasminogen activation and cell detachment. Our results
      suggest that plasmin-mediated cell detachment could contribute to the
      pathological effects of Abeta in diseased brain.

PMID- 15737741
TI  - Disinhibition of neurotrophin-induced dorsal root ganglion cell neurite outgrowth
      on CNS myelin by siRNA-mediated knockdown of NgR, p75NTR and Rho-A.
AB  - The presence of multiple axon growth inhibitors may partly explain why central
      nervous system axons are generally incapable of regenerating after injury. Using
      RNA interference (RNAi) in dorsal root ganglia neurons (DRGN), we demonstrate
      siRNA-mediated silencing of components of the inhibitory signalling cascade,
      including p75NTR, NgR and Rho-A mRNA, of 70%, 100% and 100% of the relevant
      protein, respectively, while changes in neither protein levels nor cellular
      immunoreactivity were detected using the relevant scrambled siRNA control
      sequences. Importantly, after 48 h in culture after siRNA-mediated knockdown of
      Rho-A, neurite outgrowth was enhanced by 30% compared to that after p75NTR and
      50% after NgR silencing. By 3 days, a 5-, 3.5- and 6.5-fold increase in betaIII
      tubulin protein levels were observed compared to controls without siRNA after
      knockdown of p75NTR, NgR and Rho-A, respectively. Together, these results suggest
      that Rho-A knockdown might be the most effective target for a disinhibition
      strategy to promote CNS axon regeneration in vivo.

PMID- 15737742
TI  - The MAP kinase pathway is upstream of the activation of GSK3beta that enables it
      to phosphorylate MAP1B and contributes to the stimulation of axon growth.
AB  - In pheochromocytoma 12 (PC12) cells and sympathetic neurons, nerve growth factor
      (NGF) engagement with the tropomyosin-related tyrosine kinase (TrkA) receptor
      activates the serine/threonine kinase glycogen synthase kinase 3beta (GSK3beta),
      enabling it to phosphorylate the microtubule-associated protein 1B (MAP1B).
      GSK3beta phosphorylation of MAP1B acts as a molecular switch to regulate
      microtubule dynamics in growing axons, and hence the rate of axon growth. An
      important question relates to the identification of the upstream pathway linking
      the activation of GSK3beta with TrkA engagement. TrkA can utilise a number of
      intracellular signalling pathways, including the mitogen-activated protein kinase
      (MAPK) pathway and the phosphatidylinositol-3 kinase (PI3K) pathway. We now show,
      using pharmacological inhibitor studies of PC12 cells and sympathetic neurons in
      culture and in vitro kinase and activation assays, that the MAPK pathway, and not
      the PI3K pathway, links NGF engagement with the TrkA receptor to GSK3beta
      activation in PC12 cells and sympathetic neurons. We also show that activated
      GSK3beta is a small fraction of the total GSK3beta present in developing brain
      and that it is not part of a multiprotein complex. Thus, NGF drives increased
      neurite growth rates partly by coupling the MAPK pathway to the activation of
      GSK3beta and thereby phosphorylation of MAP1B.

PMID- 15737743
TI  - The promoter of the mouse odorant receptor gene M71.
AB  - From a repertoire of approximately 2000 odorant receptor (OR) alleles in the
      mouse genome, a mature olfactory sensory neuron (OSN) is thought to choose only
      one functional allele of one OR gene for expression. OSNs that express a given OR
      gene are scattered throughout an epithelial region that is gene specific. The DNA
      sequences that enable OR gene choice and specify the epithelial pattern are not
      known. Within the upstream regions of several mouse, rat, and human OR genes, we
      have previously recognized putative homeodomain and O/E-like binding sites in
      proximity to each other. Here, we define a minimal promoter region for expression
      of the mouse OR gene M71 with small transgenes. This region contains a
      homeodomain and an O/E-like binding site. Combined mutations in both sites
      abolish transgene expression. When identical mutations are introduced at the
      endogenous M71 locus by gene targeting, the number of M71-expressing OSNs is
      reduced by a factor of three and the epithelial pattern is ventralized. The
      stronger impact observed with the mutant transgenes compared to the targeted
      mutations may reflect a multiplicity of regulatory sites within the OR gene
      cluster. We propose that these homeodomain and O/E sites regulate the probability
      of M71 gene choice differentially across the olfactory epithelium.

PMID- 15737744
TI  - Netrin-1 and slit-2 regulate and direct neurite growth of ventral midbrain
      dopaminergic neurons.
AB  - We investigated the roles of netrin-1 and slit-2 in regulation and navigation of
      dopamine (DA) axon growth using an explant culture preparation of embryonic
      ventral midbrain (embryonic day 14) and a co-culture system. We found that netrin
      1 protein significantly enhanced DA axonal outgrowth and promoted DA axonal
      outgrowth in a co-culture system of netrin-1 expressing cells. Such effects were
      mediated by the receptor DCC as demonstrated by antibody perturbation of the DCC
      receptor. In contrast, slit-2 inhibited DA neuron extensions and repelled DA
      neurite growth. These slit-2 activities required robo receptors since the reduced
      neurite extension was abolished by addition of excess robo receptors. In this
      system, netrin-1 stimulated and slit-2 opposed DA neurite growth. Such regulation
      may be important for DA axonal maintenance, regeneration, and phenotypic target
      recognition.

PMID- 15737745
TI  - Neuronal activity regulates the developmental expression and subcellular
      localization of cortical BDNF mRNA isoforms in vivo.
AB  - Activity-dependent changes in BDNF expression have been implicated in
      developmental plasticity. Although its expression is widespread in visual cortex,
      developmental regulation of its different transcripts by visual experience has
      not been investigated. Here, we investigated the cellular expression of different
      BDNF transcripts in rat visual cortex during postnatal development. We found that
      transcripts I and II are expressed only in adults but III and IV are expressed
      from early postnatal stage. Total BDNF mRNA is expressed throughout the age
      groups. Transcripts III and IV show a differential intracellular localization,
      while former was detected only in cell bodies, latter is present both in cell
      bodies and dendritic processes. Inhibition of visual activity decreases the
      levels of exons, with exon IV transcript almost disappearing from dendrites. In
      vitro experiments also confirmed the above results, indicating activity-dependent
      regulation of different BDNF promoters with specific temporal and cellular
      patterns of expression in developing visual cortex.

PMID- 15737746
TI  - Differential endocytic sorting of p75NTR and TrkA in response to NGF: a role for
      late endosomes in TrkA trafficking.
AB  - NGF binds to two receptors, p75NTR and TrkA. The endosomal trafficking of
      receptors is of emerging importance for the understanding of their signaling. We
      compared the endocytic trafficking of the two NGF receptors in PC12 cells. Both
      p75NTR and TrkA were internalized in response to NGF and colocalized with early
      endosomes. However, surprisingly, the subsequent endosomal trafficking paths of
      both NGF receptors diverged: whereas p75NTR recycled back to the surface, TrkA
      moved to late endosomes and underwent lysosomal degradation. By performing
      subcellular fractionations of NGF stimulated PC12 cells, tyrosine-phosphorylated
      TrkA was recovered in fractions corresponding to late endosomes. This implicates
      these organelles as novel endosomal NGF signaling platforms. Furthermore, the
      trafficking of NGF receptors could be manipulated by pharmacological means.
      Disrupting p75NTR recycling diminished TrkA activation in response to low
      concentrations of NGF, demonstrating a functional role for the recycling of
      p75NTR.

PMID- 15737748
TI  - Physiology of continuous blood flow in recipients of rotary cardiac assist
      devices.
AB  - The beating heart and the resultant pulse wave have been a symbol of life for
      centuries. The development history of roller pumps for cardiopulmonary bypass
      shows that the human body tolerates non-pulsatile blood flow, at least for short
      term support. Over the last few years, many types of rotary blood pumps have been
      developed for clinical use in patients requiring mid- to long-term support.
      Although early clinical experiences in patients with long-term support have been
      promising, the matter of whether pulsatile flow is needed or not remains
      controversial. Therefore, this review summarizes the observed clinical
      consequences of continuous blood flow in patients supported by rotary blood pumps
      and relates these consequences to underlying experimental studies.

PMID- 15737747
TI  - Activation of integrin alpha5beta1 delays apoptosis of Ntera2 neuronal cells.
AB  - Integrins are dynamic membrane proteins that mediate adhesion of cells to the
      extracellular matrix. Integrins initiate signal transduction, alone and
      cooperatively with growth factor receptors, and regulate many aspects of cell
      behavior. We report here that alpha5beta1-mediated adhesion of Ntera2 neuronal
      cells to fibronectin decreased apoptosis in response to serum withdrawal.
      Adhesion induced phosphorylation of FAK, and strongly increased the AKT
      phosphorylation induced by growth factors, demonstrating for the first time in
      neuronal cells that integrin-mediated adhesion and growth factors cooperate to
      regulate AKT activity. Integrins exist on cells in different activation states,
      and cell survival on fibronectin was enhanced by the antibody 12G10, that
      modulates the conformation of beta1 in favor of its active form. The antibody
      12G10 specifically delayed loss of phosphorylation of AKT on serine 473, and GSK
      3beta on serine 9, induced by serum withdrawal, suggesting that these kinases are
      critical sensors of integrin activation on neuronal cells.

PMID- 15737749
TI  - Expression of the FAST-1 transcription factor in coronary artery transplant
      vasculopathy and activated vascular smooth muscle cells.
AB  - BACKGROUND: The activation of vascular smooth muscle cells (VSMCs) causes most of
      the obliterative vasculopathy responsible for solid-organ allograft failure.
      Identification of genes expressed in activated VSMCs may provide clues to the
      pathogenesis and progression of cardiac allograft vasculopathy (CAV). METHODS: We
      performed cDNA micro-array analysis of mRNA isolated from a healthy human
      coronary artery, from a coronary artery from a patient with CAV, and from
      quiescent and stimulated cultured human coronary artery VSMCs. Western blot
      analysis and immunohistochemistry verified fork-head activin signal transducer 1
      (FAST-1) expression. RESULTS: Fold-change analysis determined that increased
      expression of a transcription factor involved in transforming growth factor beta
      (TGF-beta) signaling, FAST-1, was induced in arteries with CAV and in activated
      VSMCs, compared with normal and unstimulated cells. Western blotting confirmed
      increased FAST-1 expression in arteries with CAV vs normal arteries and arteries
      from failing hearts and confirmed increased expression in cultured VSMCs
      stimulated with a variety of cytokines. Immunohistochemical analysis determined
      that FAST-1 expression localized to neo-intimal VSMCs in rejecting arteries. In
      cultured VSMCs, FAST-1 immunolocalizes to the nucleus after TGF-beta stimulation.
      CONCLUSIONS: These results demonstrate differential expression of the FAST-1 gene
      in the VSMC response to inflammatory stimuli. Considering the significant role of
      TGF-beta in vascular fibroproliferative diseases, this work suggests that FAST-1
      may participate in the VSMC response to injury and may represent a potential
      molecular target for modulating the progression of CAV.

PMID- 15737750
TI  - Injury of the coronary endothelium at implantation increases endothelial
      dysfunction and intimal hyperplasia after heart transplantation.
AB  - BACKGROUND: Coronary endothelial dysfunction occurs early after heart
      transplantation and predicts the development of intimal thickening characteristic
      of cardiac allograft vasculopathy. OBJECTIVES: To assess the effects of removal
      of the endothelium by balloon injury of coronary arteries of allografts without
      rupture of the internal elastic lamina at the time of implantation and on
      coronary endothelial dysfunction, and to assess the development of accelerated
      atherosclerosis after heart transplantation. METHODS: A porcine model of
      heterotopic heart transplantation with preoperative immunologic typing, enabling
      progressive rejection without immunosuppression, was used to study the effect of
      endothelial removal on these 2 end points. Endothelium-dependent relaxations of
      epicardial coronary arteries from allografts submitted to endothelial denudation
      after harvest, arteries from allografts not undergoing denudation, and native
      coronary arteries were compared 30 days after graft implantation by using
      standard organ chamber experiments. Intimal thickening was measured by light
      microscopy with a semiquantitative scale (0 to 4+ grading). RESULTS: Relaxations
      to serotonin and to bradykinin were significantly decreased in denuded arteries
      compared with nondenuded allograft arteries. There was a significant increase in
      the incidence of severe intimal hyperplasia in denuded arteries compared with
      nondenuded arteries, which were both significantly increased compared to native
      coronary arteries. CONCLUSIONS: Endothelial injury at implantation worsens the
      endothelial dysfunction as a result of rejection after heart transplantation and
      compounds the intimal thickening leading to cardic allograft vasculopathy. All
      efforts should be deployed to maintain a morphologically intact and functional
      endothelium at the time of graft implantation.

PMID- 15737751
TI  - The case for selective re-issuance of medical certificates to allow pilots who
      have received a heart transplant to resume flying.
AB  - BACKGROUND: Cardiac transplant recipients have been regarded as not medically fit
      to fly an airplane. Recently, the Federal Aviation Administration decided to re
      examine this policy and, in response, this study was undertaken to determine the
      risk of death from any cause and sudden-onset death in heart transplant
      recipients during the 12 months after an annual evaluation. METHODS: Of 6,510
      patients undergoing primary orthotopic cardiac transplantation enrolled in the
      Cardiac Transplant Research Database (CTRD), 4,978 patients survived for at least
      1 year and formed the basis of this study. Risk factors for death from any causes
      and sudden-onset death (a composite of causes of death that could conceivably
      result in a pilot's incapacitation) were determined during the 12-month period
      after an anniversary evaluation. Patients were re-entered into the analysis at
      each evaluation, resulting in a total of 23,575 anniversary evaluations. RESULTS:
      The presence of coronary allograft vasculopathy (CAV), left ventricular systolic
      dysfunction, history of rejection, malignancy, infection and pre-transplant
      insulin-dependent diabetes were associated with an increased risk of death from
      any cause and sudden-onset death during the 12-month period after an evaluation.
      Based on the absence of these risk factors, a group of heart transplant
      recipients could be defined with a 12-month risk of death from any cause of 1.0%
      and of sudden-onset death of 0.3% (which is identical to the mortality rate of a
      matched population from the U.S. life-table). CONCLUSION: Using these identified
      risk factors, a group of heart transplant recipients can be defined that are
      potentially medically certifiable to fly without compromising aviation safety.

PMID- 15737752
TI  - Time course of physical reconditioning during exercise rehabilitation late after
      heart transplantation.
AB  - BACKGROUND: Exercise rehabilitation improves physical capacity in heart
      transplant recipients. The time course of physical reconditioning and skeletal
      muscle adaptation late after transplantation are unknown. METHODS: Twenty-one
      heart transplant recipients, at 5.2 +/- 2.1 years after transplantation,
      completed 1 year of an individually tailored home ergometer-training program (2.1
      +/- 0.7 sessions weekly with matched heart rates, intensity at 10% below
      anaerobic threshold). We analyzed time course of physical reconditioning data for
      each home-training session (n = 2,396). Constant-load tests with consistent blood
      lactate concentrations were performed quarterly (n = 105) to estimate the time
      course of skeletal muscle adaptation. Nine heart transplant recipients served as
      a control group (CG). RESULTS: After 12 months, exercise capacity for matched
      heart rates (112 +/- 11 beats/min; CG, 114 +/- 8 beats/min) increased by 35% +/-
      19% (from 43 +/- 14 to 58 +/- 18 W; p < 0.001; CG, 53 +/- 18 to 54 +/- 18 W); 24%
      of the increase was caused by improved skeletal muscle function and 11% by
      central functioning. Physical reconditioning showed its greatest increase within
      the first 3 months (+18%; p < 0.001); 50% of the increase consisted of better
      skeletal muscle or central functioning. Between the 4(th) and 12(th) months,
      exercise capacity increased continuously (+15%; p < 0.001), mainly because of
      better skeletal muscle functioning. CONCLUSIONS: The persistent improvement in
      exercise capacity along with consistent lactate concentrations during 12 months
      of training indicates that exercise training could counteract the negative side
      effects of immunosuppressive treatment on skeletal muscles. Even late after heart
      transplantation, physical training should be performed regularly to prevent the
      accelerated decrease in exercise capacity and in skeletal muscle function.

PMID- 15737753
TI  - Evaluation of factors damaging the bronchial wall in lung transplantation.
AB  - BACKGROUND: Lung transplantation has become important in treating end-stage lung
      disease; however, bronchial complications are common. Lack of bronchial arterial
      circulation, ischemic time, and acute rejection episodes may damage the bronchial
      wall. In this study, we analyzed factors that may hamper bronchial airway
      healing, requiring intervention after lung transplantation. METHODS: We collected
      data from a consecutive series of 81 transplantations performed between 1993 and
      2002 and evaluated recipients for bronchial complications. In 30 single and 51
      sequential bilateral lung transplantations, a total of 132 anastomoses were
      performed. Four patients (3 bilateral and 1 single lung transplant recipients who
      died within the first 14 post-operative days were excluded from the analysis.
      Finally, 125 lung grafts remained for statistical analysis of factors influencing
      bronchial complications. RESULTS: Peri-operative mortality was 8.9%. Eleven
      patients (14.7%) experienced severe bronchial complications in 16 of 125
      evaluated bronchial anastomoses (12.8%) and required surgical treatment or
      bronchoscopic interventional therapy. In a multivariate logistic regression
      model, severe reperfusion edema (adjusted odds ratio, 8.3; p = 0.002) and
      rejection episode within the 1st post-operative month (adjusted odds ratio, 4.1;
      p = 0.036) were associated with bronchial complications. Using the univariate
      model, we found that factors such as interleukin-2-antibody induction therapy,
      immunosuppression, or bronchial anastomotic technique had significant influence
      on bronchial healing, whereas we could not confirm this when using multivariate
      anasysis. CONCLUSIONS: Preventing reperfusion edema with optimized lung
      preservation and with early and aggressive medical treatment or mechanical
      hemodynamical support (e.g., veno-arterial extra corporal membrane oxygenation
      are necessary to avoid prolonged ventilation dependence, which may result in
      bronchial complications. Furthermore, avoiding early rejection episodes promotes
      uncomplicated bronchial healing.

PMID- 15737754
TI  - Psychomotor performance in lung transplant recipients: simple reaction time.
AB  - BACKGROUND: Many transplant recipients report difficulty completing fine motor
      activities such as eating, writing and manipulating buttons. These impairments
      are thought to stem from the immunosuppressive medications being taken by these
      patients. The purpose of this study was to examine central and peripheral
      processes and the force regulation involved in producing appropriate and quality
      movement in lung transplant recipients. METHODS: Fifty-one right-handed subjects
      were recruited from 3 study groups (17 in each group): Group 1, lung transplant
      recipients (LTR); Group 2, subjects with advanced emphysema; and Group 3, healthy
      adult controls. Each subject completed a fine motor and gross motor simple
      reaction time task. Central processing was examined by measuring pre-motor time,
      peripheral processing was measured by motor time, and force regulation was
      measured using movement time. A 3 x 5 multivariate analysis of co-variance
      (MANCOVA) was utilized to examine group differences, with the performance on the
      6-minute walk test serving as co-variant. Correlation analyses were conducted to
      examine the relationship between medication and psychomotor performance. RESULTS:
      The lung transplant recipient group exhibited a longer movement time and a trend
      toward longer pre-motor times. There was also a significant relationship between
      medication and movement time. CONCLUSIONS: The results support the hypothesis
      that lung transplant recipients have deficits in psychomotor performance, which
      is consistent with the literature showing that immunosuppressive medications and
      hypoxia have adverse effects on skeletal muscle. This line of research is
      relevant to the restoration of function and improvement in quality of life of
      LTR.

PMID- 15737755
TI  - Efficacy of Multiglycosidorum tripterygii for rat tracheal allografts.
AB  - BACKGROUND: A new immunosuppressant must be developed because graft rejection
      remains the leading cause of death after lung transplantation. We evaluated the
      efficacy of Multiglycosidorum tripterygii as a new immunosuppressant using a
      heterotopic rat tracheal allotransplantation model. METHODS: We performed short-
      and long-term experiments using a short-course of treatment with
      Multiglycosidorum tripterygii. To assess the immunosuppessive power of
      Multiglycosidorum tripterygii, we compared its efficacy (at 90, or 150 mg/kg/day)
      with that of tacrolimus (at 0.5, 1.0, or 1.5 mg/kg/day) at 4 weeks after
      transplantation. We then evaluated the effect of 150 mg/kg/day of
      Multiglycosidorum tripterygii treatment at 12 weeks after transplantation.
      RESULTS: The efficacy of 150 mg/kg/day Multiglycosidorum tripterygii was superior
      to that of 90 mg/kg/day of the same drug and was comparable to that of 1.0
      mg/kg/day tacrolimus, as demonstrated by morphologic assessment of the graft.
      Treatment with 150 mg/kg/day Multiglycosidorum tripterygii maintained graft
      morphology for 4 weeks but could not maintain graft viability for 12 weeks.
      Animals tolerated this dosage of Multiglycosidorum tripterygii for 12 weeks after
      administration. CONCLUSIONS: We conclude that the efficacy of Multiglycosidorum
      tripterygii is acceptable for rat tracheal allografts. Further studies are
      necessary to investigate Multiglycosidorum tripterygii treatment for clinical use
      in humans.

PMID- 15737756
TI  - Induction therapy after cardiac transplantation: a comparison of anti-thymocyte
      globulin and daclizumab in the prevention of acute rejection.
AB  - BACKGROUND: Induction therapy with antibodies decreases and delays early
      allograft rejection. We compared the safety and efficacy of daclizumab and anti
      thymocyte globulin (ATG) with respect to the frequency and severity of acute
      cardiac allograft rejection in heart transplant recipients. METHODS: Forty
      sequential adult patients were retrospectively studied. In the first 20 patients
      ATG (2.5 mg/kg daily for 3 to 5 days peri-/and post-operatively) was used as
      induction therapy and, in the remaining 20 patients, daclizumab (1 mg/kg peri
      operatively and every 2 weeks thereafter for a total of 5 doses) was used. A
      standard triple-drug immunosuppression regimen was administered to all patients.
      RESULTS: Baseline characteristics and trough levels of cyclosporine in the 2
      groups were similar. During the induction period, defined as the first 3 months,
      12 acute rejection episodes requiring treatment (ISHLT Grade > or =2) occurred in
      the ATG group and 9 in the daclizumab group (p > 0.05). However, the number of
      biopsies with Grade 1 rejection was increased >2-fold in the daclizumab group (n
      = 35) compared with the ATG group (n = 17; p = 0.04). The total number of
      biopsies performed within the first 3 months increased by 26% in the daclizumab
      group. The number and severity of rejection episodes after 3 months was similar
      in the 2 groups. The overall occurrence of bacterial infections was significantly
      higher in the ATG group than in the daclizumab group (p = 0.05). CONCLUSIONS: ATG
      and daclizumab are equally effective in preventing acute rejections requiring
      treatment (ISHLT Grade > or =2). Due to the significantly greater frequency of
      Grade 1 rejections, daclizumab was found to be associated with an increased
      number of additional biopsies for monitoring rejection status. This implies
      additional costs to the transplant program, and the long-term implications of the
      increased number of low-grade rejection episodes remains to be determined.

PMID- 15737757
TI  - The prognostic use of right heart catheterization data in patients with advanced
      heart failure: how relevant are invasive procedures in the risk stratification of
      advanced heart failure in the era of neurohormones?
AB  - BACKGROUND: Right heart catheterization long has been a routine investigation in
      advanced heart failure, and its measurements have been linked variably to
      prognosis. However, in the modern era, newer potential markers of prognosis are
      coming to light. This study reconsiders the use of right heart catheterization
      data and compares their use to that of N-terminal pro-brain natriuretic peptide
      (NT-proBNP), a neurohormone linked with prognosis in chronic heart failure.
      METHODS: We assessed prospectively the prognostic potential of baseline right
      heart catheterization data in 97 consecutive patients with advanced heart failure
      referred to the Scottish Cardiopulmonary Transplant Unit for consideration of
      cardiac transplantation. Patients underwent baseline routine investigation,
      including right heart catheterization and blood draws for NT-proBNP analysis.
      Patients were observed for a median of 370 days. RESULTS: The primary end-point
      of all-cause mortality was reached in 17 patients (17.5%), and the secondary end
      point of all-cause mortality or urgent cardiac transplantation was reached in 21
      (21.6%) patients. Univariate predictors of all-cause mortality included pulmonary
      artery systolic pressure (PASP), pulmonary artery wedge pressure (PAWP), and NT
      proBNP concentration greater than their median values. Univariate predictors of
      the secondary end-point included right atrial pressure, PASP, PAWP, and NT-proBNP
      concentration greater than their median values, and left ventricular ejection
      fraction, cardiac output, and cardiac index less than their median values. In
      multivariate analyses, however, only NT-proBNP concentration remained an
      independent predictor of all-cause mortality. Both NT-proBNP concentration and
      PAWP were independent predictors of all-cause mortality and of the need for
      urgent cardiac transplantation. CONCLUSION: Baseline data from routine right
      heart catheterization are of limited prognostic use in advanced heart failure. A
      baseline NT-proBNP concentration is a superior, non-invasive method of risk
      stratification in this era of measuring neurohormones.

PMID- 15737758
TI  - Relationship between bridging with ventricular assist device on rejection after
      heart transplantation.
AB  - BACKGROUND: Ventricular assist devices (VADs) are commonly used to bridge
      patients to heart transplantation. Recipients of VADs may develop anti-human
      histocompatibility leukocyte antigen antibodies, as reflected by elevated panel
      reactive antibodies (PRA). The purpose of this study was to evaluate the
      relationship between bridging with VAD before heart transplantation and
      development of cellular rejection, humoral rejection, and allograft vasculopathy
      after transplantation. METHODS: Data on all patients who underwent cardiac
      transplantation between July 1994 and February 2001 at Rush Presbyterian St
      Luke's Medical Center were retrospectively reviewed. Data collected included sex,
      age, etiology of cardiomyopathy, percentage panel reactive antibodies (by
      cytotoxic method), type and duration of mechanical circulatory support,
      transfusion history, rejection history (both cellular and humoral) after cardiac
      transplantation, and development of allograft vasculopathy. Cellular rejection
      was treated when International Society of Heart and Lung and Transplantation
      Grade 2 or greater in the first 12 months after transplant and Grade 3 or greater
      after 12 months and treated with intensification of immunosuppression. Humoral
      rejection was defined clinically as allograft dysfunction by echocardiography
      without evidence of cellular rejection on endomyocardial biopsy or allograft
      vasculopathy. Allograft vasculopathy was defined by presence of any degree of
      luminal narrowing or pruning of distal vessels by coronary arteriography.
      Statistical analyses were performed by chi-square test, Fisher's exact test, and
      Wilcoxon rank sum test, as appropriate. RESULTS: Ninety-eight patients underwent
      cardiac transplantation during the study period (87 men, mean age 49 years, 46
      ischemic etiology). Of these, 48 were bridged with HeartMate VAD (20 patients
      received vented electric device, 28 received pneumatic device). Nineteen percent
      of VAD patients had a peak pretransplant PRA > or =10% vs 2% of patients without
      VAD (p = 0.014). PRA > or =10%, use of VAD, or duration of VAD support did not
      predict development of humoral rejection. Use of VAD did not predict development
      of cellular rejection or allograft vasculopathy. VAD use was not associated with
      sudden death after heart transplantation. In the entire group of 98 patients,
      neither humoral nor cellular rejection predicted development of allograft
      vasculopathy. Longer ischemic time correlated with increased cellular rejection
      and humoral rejection after transplantation (p = 0.01). CONCLUSIONS: Some
      patients bridged to cardiac transplantation with VADs have increased PRA before
      heart transplantation, but this does not appear to translate into increased risk
      of either humoral or cellular rejection after transplantation or development of
      allograft vasculopathy as detected by coronary angiography.

PMID- 15737759
TI  - Graft coronary artery disease in murine cardiac allografts: proposal to meet the
      need for standardized assessment.
AB  - BACKGROUND: Inconsistency exists in assessing the severity of graft coronary
      artery disease (GCAD) in studies that use mouse models. The central issue
      associated with this inconsistency is the lack of a standardized approach for
      assessing mouse GCAD. METHODS: We propose a new histologic definition of GCAD
      based on 3 successive stages (endotheliitis, premature lesion, and mature lesion)
      that mark the progression of this condition. In addition to these qualitative
      measures of GCAD, we propose including 2 additional morphometric parameters
      (percentage of luminal narrowing and intima-to-media ratio) and a measure of
      distribution (percentage of affected vessels) in the routine quantification of
      GCAD. RESULTS: We introduce 2 new mouse models of GCAD as examples that satisfy
      these criteria. CONCLUSION: The proposed assessment criteria may simplify data
      collection and interpretation of results in various models of GCAD.

PMID- 15737760
TI  - Changes in radiographic abnormalities in organ donors: associations with lung
      transplantation.
AB  - BACKGROUND: Only 20% of organ donors are considered suitable for lung
      transplantation. No extensive study exists that has evaluated changes in thoracic
      radiographic abnormalities in organ donors. The purpose of this study was to
      determine the impact of radiographic abnormalities on successful transplantation.
      METHODS: In a retrospective survey of 110 organ donors, chest radiographs (N =
      417) taken during the initial 24 hours after admission and just before organ
      harvest were evaluated for 9 radiographic criteria, radiographic diagnoses and
      clinical characteristics and their association with lung transplantation.
      RESULTS: Initial lung densities were present in 37% of lungs; there were
      bilateral infiltrates in 25% of cases. During evaluation (69.7 +/- 60 hours), 38%
      of right lungs and 28% of left lungs improved radiographically. Up to 51% of
      lungs with initial infiltrates resolved completely. Worsening of lung infiltrates
      was more common in the non-transplant group (p = 0.02); however, improvement in
      densities was not associated with transplantation (p = 0.6). Multivariate
      analysis determined that moderate and severe lung densities (OR 7.68, p = 0.01;
      OR 10.8, p = 0.004) and bilateral infiltrates (OR 4.79, p = 0.02) were
      independent predictors of rejection for transplantation. With densities removed
      from the model, the number of abnormal diagnoses on the final films was an
      independent predictor of rejection for transplantation (OR 3.23, p = 0.003).
      CONCLUSIONS: More than 33% of proposed organ donors initially have lung
      infiltrates, with >33% showing improvement or resolution, but this improvement
      does not impact on procurement. Multiple abnormal radiographic diagnoses also
      contribute to transplant rejection.

PMID- 15737761
TI  - Lessons learned from the first application of the DeBakey VAD Child: an
      intracorporeal ventricular assist device for children.
AB  - We report and describe the design and the first clinical implantation of the
      DeBakey ventricular assist device (VAD) Child, a pediatric intracorporeal left
      ventricular assist device, in a 6-year-old girl. The risk-benefit of novel
      technologies in advanced heart failure and the lessons learned by our experience
      are important to consider in hopes that other centers (where this device is now
      available) may benefit.

PMID- 15737762
TI  - Placement of a left ventricular assist device in a patient with dextrocardia.
AB  - Dextrocardia most commonly presents in the setting of situs inversus, but it may
      occur as an isolated anomaly with normal position of the abdominal organs. Herein
      we present a 54-year-old man with ischemic cardiomyopathy and dextrocardia with
      normal position of the abdominal organs who presented with an exacerbation of
      congestive heart failure requiring inotropic support as well as mechanical
      ventilation. An implantable, wearable left ventricular assist device was placed
      in this patient to allow for ambulation and eventual discharge home. The patient
      survived 4 months before he developed pneumonia and expired.

PMID- 15737763
TI  - Successful transplantation of an older donor heart with documented myocardial
      bridging: a case report.
AB  - Myocardial bridging, the overlying of myocardial tissue onto epicardial coronary
      arteries, is an anatomic variant that is widely present in the general
      population. This condition can be associated with reduced forward coronary flow.
      Once these hearts are identified in potential donors by either visual inspection
      or coronary catheterization, they may no longer be considered suitable for
      transplantation. We present a case study that successfully utilized such a heart
      explanted from an older donor with "bench" myotomy repair before implantation.

PMID- 15737764
TI  - Treatment of parainfluenza virus 3 pneumonia in a cardiac transplant recipient
      with intravenous ribavirin and methylprednisolone.
AB  - A 59-year-old man developed a lower respiratory tract infection 10 years after
      orthotopic cardiac transplantation. He did not respond to broad-spectrum
      antibiotic and antifungal treatment. Parainfluenza virus type 3 was the causative
      organism, and he was successfully treated with intravenous ribavirin and
      methylprednisolone.

PMID- 15737765
TI  - Use of recombinant factor VII to control bleeding in a patient supported by right
      ventricular assist device after heart transplantation.
AB  - A 48-year-old man undergoing orthotopic heart transplantation for ischemic
      cardiomyopathy developed severe right heart failure. Severe intractable bleeding
      complicated implantation of a right ventricular assist device. Treatment with 9.6
      mg of recombinant activated factor VII stopped the bleeding, and the patient
      could be transferred to the intensive care unit. This is the first reported case
      of the successful use of recombinant activated factor VII to control bleeding
      with subsequent right ventricular assist device function.

PMID- 15737766
TI  - Left ventricular apical infection and rupture complicating left ventricular
      assist device explantation in 2 women with postpartum cardiomyopathy.
AB  - Postpartum cardiomyopathy is rare form of cardiac failure, with the potential for
      cardiac function to recover to normal. When medical therapy fails to control
      symptoms or haemodynamic stability, circulatory support with a ventricular assist
      device may be considered as a bridge to cardiac transplantation. We describe 2
      patients with severe postpartum cardiomyopathy, in whom cardiac function
      recovered sufficiently during mechanical circulatory assistance to enable device
      explantation. Bacteremia during device support was treated with chronic
      suppressive antibiotics, yet after cannula explantation and ventricular repair,
      residual infection led to destruction of the primary repair, with formation of a
      left ventricular pseudoaneurysm. This is a complication of device support not
      previously reported. Surgery was necessary to repair the infected ventricular
      cannula site. Both patients recovered; however one patient developed recurrent
      cardiomyopathy 4 months later.

PMID- 15737767
TI  - Coronary artery vasospasm causing acute myocardial infarction in a heart
      transplant recipient.
AB  - The etiology of cardiac allograft vasculopathy is not known, but may be preceded
      by both endothelial cell and smooth muscle dysfunction of the epicardial coronary
      arteries. We here report a case of acute, reversible coronary artery vasospasm
      which caused a myocardial infarction in a cardiac transplant recipient. The
      patient had a complex post-transplant course, including an episode of severe
      vascular rejection several months before this presentation. Interestingly, the
      event was captured in its early stages because the patient presented with chest
      pain: a rare event because of the denervation of the transplanted heart. Our
      ability to document the etiology of this patient's myocardial infarction supports
      the concept that cardiac allograft vasculopathy is a progressive disease that, in
      its early stages, may include a reversible component of abnormal vasoreactivity.

PMID- 15737768
TI  - Since school-based tobacco prevention programs do not work, what should we do?

PMID- 15737769
TI  - Mediterranean and Middle East Action Group for Adolescent Medicine (M.A.G.A.M.):
      origins, development and aims.

PMID- 15737770
TI  - A systematic review of school-based smoking prevention trials with long-term
      follow-up.
AB  - BACKGROUND: Several systematic reviews of school-based smoking prevention trials
      have shown short-term decreases in smoking prevalence but have not examined long
      term follow-up evaluation. The purpose of this study was to conduct a systematic
      review of rigorously evaluated interventions for school-based smoking prevention
      with long-term follow-up data. METHODS: We searched online bibliographic
      databases and reference lists from review articles and selected studies. We
      included all school-based, randomized, controlled trials of smoking prevention
      with follow-up evaluation to age 18 or 12th grade and at least 1 year after
      intervention ended, and that had smoking prevalence as a primary outcome. The
      primary outcome was current smoking prevalence (defined as at least 1 cigarette
      in the past month). RESULTS: The abstracts or full-text articles of 177 relevant
      studies were examined, of which 8 met the selection criteria. The 8 articles
      included studies differing in intervention intensity, presence of booster
      sessions, follow-up periods, and attrition rates. Only one study showed decreased
      smoking prevalence in the intervention group. CONCLUSIONS: Few studies have
      evaluated the long-term impact of school-based smoking prevention programs
      rigorously. Among the 8 programs that have follow-up data to age 18 or 12th
      grade, we found little to no evidence of long-term effectiveness.

PMID- 15737771
TI  - Ethnic variation in socioenvironmental factors that influence adolescent smoking.
AB  - PURPOSE: To compare black, Hispanic and white adolescent smokers on
      socioenvironmental factors associated with smoking. METHODS: The study uses a
      cross-sectional design. A needs assessment of 1305 current, former and never
      adolescent smokers from four ethnically and geographically diverse sites in the
      United States was conducted in 1999. Two sites were selected because they
      represented urban cities in the Northeast and Midwest with a high proportion of
      black and Hispanic residents. Two additional sites were selected to recruit rural
      and suburban adolescents. From this larger sample, 181 subjects from three focal
      ethnic groups (white n = 138; black n = 24; Hispanic n = 19) who had smoked at
      least 100 cigarettes in their lifetime and were current smokers (smoked in the
      past 30 days) were included. The three ethnic groups were compared on the
      following variables of interest: peer and family influences on smoking,
      situational factors associated with smoking, places that were likely sites for
      smoking and perceptions of friends and family as potential support persons for
      quitting smoking. All data were analyzed with Chi-square analysis. RESULTS:
      Almost all (96%) of the black adolescents lived with another smoker compared to
      68% of Hispanic and 60% of whites (p = .004). Black teens were more likely to
      smoke with family members (50%) than Hispanics (5%) or whites (25%) (p = .003).
      In addition, 50% of black teens compared to 5% of Hispanics and 12% of white
      teens, reported smoking to fit in (p < .0001). Black teens in this study
      emphasized the familial and social pressures of smoking. Higher rates of
      acceptance of smoking by family members, role modeling by household members, more
      prevalent beliefs that smoking is a way to achieve belonging, and lack of
      perceived support for quitting by friends appear to influence cigarette smoking
      more for black than white or Hispanic youth. CONCLUSIONS: These preliminary
      results indicate that familial and household norms play a critical role in
      influencing cigarette smoking among black teens.

PMID- 15737772
TI  - Adolescents' knowledge, beliefs, and behaviors regarding hepatitis B: Insights
      and implications for programs targeting vaccine-preventable diseases.
AB  - PURPOSE: To gain a better understanding of adolescents' knowledge, beliefs, and
      behaviors regarding hepatitis B. METHOD: Three types of data were collected as
      part of this investigation: (a) 45 in-depth individual interviews with staff from
      20 adolescent health, sexually transmitted disease (STD), and family planning
      clinics; (b) 96 individual interviews with adolescents and young adults; and (c)
      questionnaires completed by 17,063 adolescents and young adults. All instruments
      focused on one or more of the following five topics: (a) knowledge about
      vaccines; (b) knowledge about hepatitis B; (c) barriers to vaccine acceptance,
      and ways to overcome these barriers; (d) benefits of the vaccine acceptance, and
      ways to enhance these benefits; and (e) eight hepatitis B risk factors. Interview
      data was analyzed using qualitative thematic note-based analyses. Survey data was
      analyzed using descriptive statistics and Chi-square tests. RESULTS: Adolescents
      and young adults seen in these clinics know very little about vaccinations in
      general, or hepatitis B, in particular. Adolescents exhibit low levels of
      perceived susceptibility, severity, response efficacy, and self-efficacy toward
      hepatitis B and the hepatitis B vaccine. On average, these adolescents engage in
      2.36 high-risk behaviors (the most frequent of which include sexual activity,
      body piercing, and tattooing). Those who were sexually active, had a tattoo, had
      a STD, or worked with blood were significantly more likely to begin the
      vaccination series. CONCLUSIONS: There is a clear need for additional educational
      efforts regarding both vaccinations in general, and hepatitis B in particular.
      Though adolescents are engaging in a variety of high-risk behaviors, most
      perceive their risk to be low, and therefore many are not taking the necessary
      precautions to protect themselves.

PMID- 15737773
TI  - Safety and immunogenicity of concomitant versus nonconcomitant administration of
      hepatitis B, tetanus-diphtheria, and measles-mumps-rubella vaccines in healthy
      eleven- to twelve-year-olds.
AB  - PURPOSE: To study safety and immunogenicity of concomitant administration of
      hepatitis B (HB), Tetanus-diphtheria (Td), and Measles-mumps-rubella (MMR)
      vaccines in healthy 11-12-year-olds. METHOD: One hundred ninety-seven healthy 11
      12-year-olds from the general community were randomized in an unblinded study to
      concomitant vaccination with Recombivax HB brand of HB vaccine and Td and MMR
      vaccines or to HB given at a separate time from Td and MMR vaccination. Primary
      analyses were for induction of protective immunity and safety. Secondary
      endpoints were mean geometric antibody titers for HB and a boosting effect for Td
      and MMR. Differences in immunogenicity were analyzed using the one-sided
      Pearson's Chi-square test. RESULTS: Concomitant vaccination for HB, Td, and MMR
      had a significantly increased incidence of headache, red eyes, and rash compared
      with nonconcomitant vaccination. There was no significant difference in incidence
      of serious adverse events, rates of protective immunity, or in secondary
      endpoints. CONCLUSIONS: Concomitant HB, Td, and MMR vaccination in 11-12-year
      olds is as safe and immunogenic as nonconcomitant vaccination.

PMID- 15737774
TI  - Practice of habitual and volitional health behaviors to prevent severe acute
      respiratory syndrome among Chinese adolescents in Hong Kong.
AB  - PURPOSE: To explore factors relating to the practice of habitual and volitional
      health behaviors against the severe acute respiratory syndrome (SARS) among
      Chinese adolescents in Hong Kong. METHODS: A community telephone survey was
      conducted with 230 Chinese adolescents. Random-digit dialing of the local
      residential telephone directory was used to select respondents, who were asked to
      provide information on their practice of SARS preventive health behaviors and
      associated factors as specified by the Health Belief Model. These factors
      included perceived threat of SARS, perceived benefits and barriers in practicing
      SARS preventive health behaviors, cues to action, knowledge of SARS, and self
      efficacy. Hierarchical regression analyses were conducted to determine salient
      correlates of habitual and volitional health behaviors against SARS. RESULTS:
      About 54.8% of respondents reported practicing all three recommended habitual
      health behaviors. Another 47.8% indicated consistent practice of volitional
      health behavior of facemask-wearing to prevent SARS. Results of hierarchical
      regression analyses showed that habitual health behaviors against SARS were
      related to perceived health threat and environmental cues. For facemask-wearing,
      salient correlates were environmental cues, rates of SARS habitual health
      behaviors, younger age, and perceived health threat. CONCLUSIONS: The Health
      Belief Model is useful in understanding Chinese adolescents' practice of health
      behaviors, especially volitional health behaviors.

PMID- 15737776
TI  - Follow-up evaluation of a high school eating disorders screening program:
      knowledge, awareness and self-referral.
AB  - PURPOSE: To conduct a regional, follow-up evaluation to assess the implementation
      and effectiveness of the National Eating Disorders Screening Program (NEDSP),
      conducted in high schools nationwide in the spring of 2000. METHODS: Four New
      England high schools participated in a postscreen evaluation 1 to 2 months after
      implementation of NEDSP. A 35-item, self-report postscreen survey was
      administered to students in classrooms with assistance from school health staff
      and teachers. School staff involved in the screening were also interviewed.
      Logistic regression was used to estimate the odds that students talked to an
      adult or peers about their screening score. RESULTS: Data from 592 girls and 435
      boys were included in the analysis in the four high schools participating in the
      program evaluation. NEDSP helped to identify students at risk and encouraged
      students to speak to others about their screening score and eating disorder
      symptoms. One-quarter of girls and one-fifth of boys reported talking with at
      least one adult about their EAT-26 screening score. Girls felt more strongly than
      boys that the program helped them learn about eating disorders, change their
      thinking related to eating disorders and body image, and talk to friends about
      eating disorders. Overall, the students felt that the program was helpful and
      would recommend it to their friends. CONCLUSIONS: Early detection of eating
      disorders in adolescents may shorten the interval between onset of symptoms and
      treatment, which has the potential to reduce the length of illness and morbidity
      associated with untreated eating disorders. Our findings suggest that high-school
      based screening may be an effective way to facilitate early detection of eating
      disorder symptoms in adolescents.

PMID- 15737775
TI  - African-American adolescents' stress responses after the 9/11/01 terrorist
      attacks.
AB  - PURPOSE: To examine the impact of indirect exposure to the 9/11/01 attacks upon
      physical and emotional stress-related responses in a community sample of African
      American (AA) adolescents. METHODS: Three months after the 9/11/01 terrorist
      attacks, 406 AA adolescents (mean age [SD] of 16.1 +/- 1.3 years) from an inner
      city high school in Augusta, GA were evaluated with a 12-item 5-point Likert
      scale measuring loss of psychosocial resources (PRS) such as control, hope,
      optimism, and perceived support, a 17-item 5-point Likert scale measuring post
      traumatic stress symptomatology (PCL), and measures of state and trait anger,
      anger expression, and hostility. Given the observational nature of the study,
      statistical differences and correlations were evaluated for effect size before
      statistical testing (5% minimum variance explained). Bootstrapping was used for
      testing mean differences and differences between correlations. RESULTS: PCL
      scores indicated that approximately 10% of the sample was experiencing probable
      clinically significant levels of post-traumatic distress (PCL score > 50). The
      PCL and PRS were moderately correlated with a r = .59. Gender differences for the
      PCL and PRS were small, accounting for 1% of the total variance. Higher PCL
      scores were associated with higher state anger (r = .47), as well as measures of
      anger-out (r = .32) and trait anger (r = .34). Higher PRS scores were associated
      only with higher state anger (r = .27). Scores on the two 9/11/01-related scales
      were not statistically associated (i.e., less than 5% of the variance explained)
      with traits of anger control, anger-in, or hostility. CONCLUSIONS: The majority
      of students were not overly stressed by indirect exposure to the events of
      9/11/01, perhaps owing to the temporal, social, and/or geographical distance from
      the event. Those who reported greater negative impact appeared to also be
      experiencing higher levels of current anger and exhibited a characterologic style
      of higher overt anger expression.

PMID- 15737777
TI  - Prevalence of eating disorders in Latina adolescents: associations with substance
      use and other correlates.
AB  - PURPOSE: To estimate the occurrence and correlates of anorexia nervosa and
      bulimia nervosa-related symptoms in a Latina sample of U.S. adolescents. METHOD:
      Approximately 1866 Latinas ranging in age from 11-20 years old are included in
      this study. These adolescents are a sub-sample from the National Longitudinal
      Survey on Adolescent Health. Along with self-reports of eating disorder-related
      variables, we measured related biological, contextual, behavioral, and
      psychosocial correlates, including use of various substances. CONCLUSION: Chi
      square analysis showed the prevalence in all Latina sub-groups was relatively
      consistent with the U.S. trends. Latinas of higher socioeconomic status were more
      at risk for eating disorders. Body dissatisfaction, negative affectivity,
      substance use, and low self-esteem were all positively correlated with eating
      disorder symptoms. These results suggest screening and treatment services are
      needed across groups of Latina adolescents.

PMID- 15737778
TI  - Anorexia nervosa in male adolescents: body image, eating attitudes and
      psychological traits.
AB  - PURPOSE: To evaluate body image and its relationship with psychological and
      behavioral traits associated with anorexia nervosa in male patients. METHODS:
      Thirty male adolescents with anorexia nervosa (AN) were compared with 421 male
      adolescents from the general population. Body image was evaluated with the
      Subjective Body Dimensions Apparatus. Eating attitudes were evaluated by the
      Eating Attitudes Test in its 26-item version (EAT-26). In 19 AN patients and 200
      boys from the comparison group, the Eating Disorders Inventory (EDI) was also
      administered. RESULTS: AN patients had higher mean scores in the EAT-26 and the
      Body Dissatisfaction scale on the EDI, but not on the other EDI scales. Both
      groups overestimated all parts of their bodies but AN patients presented a
      greater overestimation of shoulders (p = .007), hips (p = .01) and thighs (p =
      .019). Correlations in the anorexic group were high and negative between body
      overestimation and body mass index and also high but positive between
      overestimation and the EAT and the Drive for Thinness scale on the EDI.
      Overestimation did not correlate significantly with other EDI scales.
      CONCLUSIONS: Male patients with anorexia nervosa overestimate some parts of their
      bodies more often than controls; this overestimation is related to body mass
      index, abnormal eating attitudes and drive for thinness, but not to other
      psychological traits evaluated by the EDI.

PMID- 15737779
TI  - Youth risk behavior survey: Bangkok, Thailand.
AB  - PURPOSE: To identify the prevalence of risk behaviors and related risk factors in
      adolescents in Bangkok, Thailand. METHODS: Youth risk behavior survey
      questionnaires were collected from 2311 adolescents in 8 schools, 13 communities
      and 2 Juvenile Home Institutions from January to February 2001. Their mean age
      was 15.5 +/- 1.8 years, and 59% were female. Risk factors of interest were
      gender, parental marital status, socioeconomic status, family relationship,
      parental drug addiction, peer group, loneliness, self-esteem, and school
      performance. Multiple logistic regression was used to identify significant risk
      factors associated with each risk behavior. RESULTS: The risk behaviors leading
      to traffic accidents were rarely or never having worn a seat belt (30.6%) or
      helmet while bicycling (66.9%) and while motorcycling (50.1%), riding with
      drivers who had consumed alcohol (18.8%), and driving after consuming alcohol
      (12.1%). The studied group carried weapons (8.5%) and has been involved in a
      violent event (31.5%). Among 13.9% who were assaulted, 6.7% needed
      hospitalization; rape was reported by 2.4%. Depression was reported by 19.9%,
      with 12% having suicidal tendencies and 8% attempting suicide. The lifetime use
      vs. heavy use prevalence of substance abuse, respectively, was: 15.4% and 3.5%
      for smoking, 37.3% and 1.7% for alcohol, 37.8% and 4.6% for amphetamine use, and
      37.9% and 0.1% for other drugs. Among the 10% who have had sexual intercourse, 1%
      were homosexual, 7.1% have never used a condom, and 2.1% resulted in pregnancy.
      Being male was a risk factor for every untoward behavior except depression. Other
      risk factors included poor self-esteem, poor school performance, and early school
      leaving. Factors relating to the family included a low socioeconomic status, poor
      relationships, broken families, and parental substance abuse. Socioenvironmental
      factors included being in a gang and loneliness. Some risk behaviors started at
      younger than 8 years old. Schools and media were given as the sources of
      information regarding sex, human immunodeficiency virus infection, and substance
      abuse. CONCLUSIONS: The prevalence of six major-risk behaviors in adolescents in
      Bangkok was significantly high. Several risk factors were identified, the
      knowledge from which may help to form preventive measures in this population.

PMID- 15737780
TI  - Psychological health and bullying behavior among adolescent prisoners: a study of
      young and juvenile offenders.
AB  - PURPOSE: To explore psychological health and behaviors indicative of direct,
      indirect and coercive bullying in a sample of adolescent offenders. METHODS: One
      hundred two juvenile (aged 15-17 years) and 100 young (aged 18-21 years)
      offenders took part. All completed the General Health Questionnaire (GHQ-28) and
      a revised version of the Direct and Indirect Prisoner behaviour Checklist (DIPC
      R). Offenders were classified into one of four categories: "pure bullies" (solely
      reporting behaviors indicative of bullying others); "bully/victims" (reporting
      behaviors indicative of bullying others and of being bullied); "pure victims"
      (only reporting "victim" behaviors); "not-involved" (not reporting any "bully" or
      "victim" behaviors). The data was analyzed using Kuder-Richardson-20, LOGIT
      Analysis, ANOVA, MANOVA, and correlations. RESULTS: Juveniles reported
      perpetrating and experiencing more bullying behavior than young offenders. Pure
      victims and bully/victims reported more symptoms associated with somatic
      concerns, severe depression, anxiety and insomnia in comparison with pure bullies
      and those not involved. Bully/victims reported more somatic symptoms and pure
      victims more social dysfunction. The psychological health profiles of pure
      bullies and those not involved were broadly similar. Indirect, direct and
      coercive victimization all correlated positively with psychological health.
      CONCLUSIONS: The current study provides evidence for an association between self
      reported psychological health and direct, indirect and coercive bullying behavior
      among an incarcerated adolescent sample. It also highlights the importance of
      viewing the "bully/victim" group as a victim group.

PMID- 15737781
TI  - Neighborhood quality and somatic complaints among American youth.
AB  - PURPOSE: This study examines the relationship between the social context of
      neighborhood and somatic complaints in a national probability sample of
      adolescents. METHODS: Structural equation modeling is used to estimate paths of
      influence between neighborhood quality and somatic complaints. An analysis of
      variance highlights the relationship between demographic characteristics and
      neighborhood quality. RESULTS: Neighborhood quality appears to play an indirect
      role in producing somatic complaints in adolescents. Linkages between correlates
      of somatic complaints, such as stressful life events, family environment,
      psychological distress, and measures of neighborhood quality are discussed.
      CONCLUSIONS: These findings emphasize the need to conceptualize adolescent
      somatization as contextually dependent and to use an ecological perspective when
      intervening with somaticizing teens.

PMID- 15737782
TI  - Low-income neighborhood barriers and resources for adolescents' physical
      activity.
AB  - PURPOSE: To investigate factors of low-income neighborhoods and households on
      physical activity with a sample of adolescents from low-income neighborhoods.
      METHODS: Middle-school-aged youth (n = 74) from a low-income neighborhood
      completed self-report surveys. Measures include vigorous exercise frequency,
      neighborhood hazards, after-school time demands, availability of facilities,
      quality of facilities, and perceived safety. Hierarchical multiple linear
      regression and Pearson product moment correlations were conducted to test
      hypotheses that more frequent physical activity would be associated with more
      available locations, better quality facilities, fewer time demands, more after
      school programs, more perceived safety, and more hazards. RESULTS: Results
      indicate that more physical activity was associated with more hours spent in
      after-school programs (r = .50, p < .001) and perception of higher quality of
      local facilities (r = .28, p < .05). Perception of safe adults at local
      facilities accounted for more variance than perception of neighborhood hazards in
      the association with physical activity even after accounting for gender, age, and
      socioeconomic status. CONCLUSIONS: Future health promotion programs should
      consider factors of after-school programs such as quality, cost, and presence of
      safe adults when attempting to increase and maintain youth physical activity in
      lower income areas.

PMID- 15737783
TI  - Extended families and adolescent well-being.
AB  - PURPOSE: To examine the association between adolescent well-being and the
      presence of non-parental adults in the household. METHODS: The sample for this
      study was obtained from the 1995 National Longitudinal Study of Adolescent
      Health. The sample consists of adolescents who reside with parents and at least
      one non-parental adult. Non-parental adults include grandparents, aunts, uncles,
      cousins, and other relatives. Two measures of adolescent well-being are examined:
      depressive symptoms and deviant behavior. Regression analyses include controls
      for family structure, parent and child characteristics, and parent-child
      relations. RESULTS: The presence of grandparents in the household is associated
      with less deviant behavior overall, and fewer depressive symptoms among Blacks.
      The presence of other adults such as aunts, uncles, and other relatives is
      associated with greater depressive symptoms overall, but less deviant behavior
      among adolescents in households with large numbers of siblings. CONCLUSIONS: The
      association between extended families and adolescent well-being is not as
      straightforward as often assumed. Results point to the need for caution when
      discussing the benefits of such families as their impact varies with outcome of
      interest, the relationship to the child, and other characteristics within the
      family.

PMID- 15737784
TI  - Body dissatisfaction, self-esteem, and overweight among inner-city Hispanic
      children and adolescents.
AB  - We examined the associations among self-reported body image, self-esteem, and
      measured body mass index (BMI) in El-Salvadoran American youth. Higher BMI was
      associated with body size dissatisfaction, lower peer esteem, and attempts to
      lose weight. Body size dissatisfaction was also significantly related to self
      esteem in these El-Salvadoran American youth.

PMID- 15737785
TI  - Friends in the 'hood: Should peer-based health promotion programs target
      nonschool friendship networks?
AB  - PURPOSE: To examine the characteristics of inner city African-American
      adolescents nonschool-based and school-based friendship networks and to explore
      the influence of these networks on health risk behavior. METHODS: We assessed
      close friendships networks in a probability sample of inner city African-American
      youth living in a single neighborhood and describe the networks and health risk
      behavior of network members. The initial probability sample was obtained via
      telephone (Random Digit Dialing [RDD] sampling) and followed up with in-person
      interviews with telephone respondents (seeds). Subsequently, seeds' friends were
      recruited and completed an in-person interview. RESULTS: A majority of friendship
      networks included some nonschool friends (57%) and 24% of networks were composed
      exclusively of nonschool friends. As expected, youth were more likely to spend
      time with school-based friends on weekdays. On weekends, youth were equally
      likely to spend time with both school and nonschool networks. Youth in the same
      friendship group tended to engage in similar behaviors. Health risk behaviors
      were high regardless of whether networks were nonschool based, mixed, or school
      based. CONCLUSIONS: The high proportion of nonschool friendships suggests that
      out-of-school networks may be an important influence in this population. Youth
      spend time with their friends, regardless of network type, on weekends, and
      weekends are a high-risk period for health-damaging behaviors. Levels of
      experience with health risk behaviors suggest that both school and nonschool
      environments require intervention. Future social influence prevention efforts
      that are broad-based are likely to have maximal impact.

PMID- 15737786
TI  - Potential for violence against teenage retail workers in the United States.
AB  - PURPOSE: To examine the working conditions of teenagers in five sites, examining
      the presence of factors associated with workplace violence and considering
      workers' concerns about safety and training to deal with violent circumstances.
      METHODS: Teenage workers, aged 14-17 years, with employment experience in retail
      industries in five sites (North Carolina; Brockton, Massachusetts; Los Angeles,
      California; Oakland, California; Philadelphia, Pennsylvania) were questioned.
      Data in North Carolina were collected by telephone interview. Parallel data from
      the other sites were obtained using self-administered questionnaires in schools.
      RESULTS: Teenage retail workers report experiences that include working alone, at
      night, and/or without supervisors present. Training about angry customers,
      robbery, and sexual harassment is less than complete. Yet, teenage retail workers
      express few concerns about safety. CONCLUSIONS: Most teenagers work while
      attending high school, with over half employed in the retail trades. Those
      working in retail experience higher rates of workplace violence than other
      workers, mostly during robberies. Working alone and at night are risk factors for
      violent victimization. Findings indicate areas of potential improvement in child
      labor practices, particularly with respect to training and supervision.

PMID- 15737787
TI  - Genetics wakes up for human sleep.

PMID- 15737788
TI  - Genetics of normal and pathological sleep in humans.
AB  - The complexity of sleep-wake regulation, in addition to the many environmental
      influences, includes genetic predisposing factors, which begin to be discovered.
      Most of the current progress in the study of sleep genetics comes from animal
      models (dogs, mice, and drosophila). Multiple approaches using both animal models
      and different genetic techniques are needed to follow the segregation and
      ultimately to identify 'sleep genes' and molecular bases of sleep disorders.
      Recent progress in molecular genetics and the development of detailed human
      genome map have already led to the identification of genetic factors in several
      complex disorders. Only a few genes are known for which a mutation causes a sleep
      disorder. However, single gene disorders are rare and most common disorders are
      complex in terms of their genetic susceptibility, environmental factors, gene
      gene, and gene-environment interactions. We review here the current progress in
      the genetics of normal and pathological sleep and suggest a few future
      perspectives.

PMID- 15737789
TI  - Nitric oxide and sleep.
AB  - Nitric oxide (NO) is a biological messenger synthesized by three main isoforms of
      NO synthase (NOS): neuronal (nNOS, constitutive calcium dependent), endothelial
      (eNOS, constitutive, calcium dependent) and inducible (iNOS, calcium
      independent). NOS is distributed in the brain either in circumscribed neuronal
      sets or in sparse interneurons. Within the laterodorsal tegmentum (LDT),
      pedunculopontine tegmentum and dorsal raphe nucleus, NOS-containing neurons
      overlap neurons grouped according to their contribution to sleep mechanisms. The
      main target for NO is the soluble guanylate cyclase that triggers an
      overproduction of cyclic guanosine monophosphate. NO in neurons of the pontine
      tegmentum facilitates sleep (particularly rapid-eye-movement sleep), and NO
      contained within the LDT intervenes in modulating the discharge of the neurons
      through an auto-inhibitory process involving the co-synthesized
      neurotransmitters. Moreover, NO synthesized within cholinergic neurons of the
      basal forebrain, while under control of the LDT, may modulate the spectral
      components of the EEG instead of the amounts of different sleep states. Finally,
      impairment of NO production (e.g. neurodegeneration, iNOS induction) has
      identifiable effects, including ageing, neuropathologies and parasitaemia.

PMID- 15737790
TI  - Sleep and depression in children and adolescents.
AB  - There is considerable research evidence suggesting that sleep is biologically
      linked to mood disorders in adults. However, polysomographic and neuroendocrine
      studies in children and adolescents have not found consistent changes in sleep
      architecture paralleling adult major depression. This review provides a detailed
      description of sleep research that has been conducted in early-onset affective
      disorders, uncovers the potential limitations of the available data, and
      formulates future research directions in this important subject.

PMID- 15737791
TI  - Sleep-disordered breathing and cardiovascular disease.
AB  - Untreated sleep apnea is a risk factor for hypertension, and CPAP treatment
      effects a blood pressure reduction comparable to that of pharmacologic
      monotherapy. Nevertheless, many current papers addressing the rapid increase in
      prevalence of hypertension and purporting to outline its management do not
      mention looking for or treating sleep apnea as a strategy. In addition to
      hypertension, virtually every adverse cardiovascular condition has been strongly
      associated with sleep disordered breathing in cross-sectional studies. There are
      also small prospective studies of the relationship between sleep-disordered
      breathing (SDB) and coronary heart disease and atrial fibrillation. Further,
      treatment studies show improvement or reduced risk of most cardiovascular
      sequelae of SDB with CPAP treatment. Beyond hypertension, which is well
      established, the strongest relationships between SDB and cardiovascular disease
      appear to be with congestive heart failure and bradyarrhythmias. Prospective
      studies are needed to confirm these relationships and to further delineate the
      risk.

PMID- 15737792
TI  - Evolutionary approaches to understanding sleep.
AB  - A major controversy over REM sleep's role in memory processing may owe to
      inadequate allowances for the highly conservative nature of evolutionary
      adaptations. The controversy hinges on whether NREM sleep, alone, retains
      primitive memory processing capabilities. The selective pressure for primitive
      sleep, is thought to have been the need to obviate conflicts between enormous
      neural processing requirements of complex visual analysis and split-second
      control of movements, on the one hand, and memory processing, on the other. The
      most efficient memory processing during mammalian and avian sleep appears to be a
      two-step process: synapses in individual component circuits of events are
      reinforced primarily by slow brain waves during NREM sleep, with the reinforced
      components temporally bound by fast waves, and manifested as dreams, during REM
      sleep. This dual action could account for partitioning of sleep periods into
      multiple NREM-REM cycles. It is proposed that in the absence of REM sleep, all
      needed memory processing can be accomplished by NREM sleep, alone, though less
      efficiently. Many symptoms of fatal familial insomnia are attributed to subnormal
      nightly reinforcement of brain circuitry because of almost total loss of sleep,
      and compensatory responses thereto during waking. During this disorder, sensory
      circuitry seemingly is spared by virtue of its supernormal reinforcement during
      almost continuous waking. Contrariwise, sparing of an adult's 'higher faculties'
      in encephalitis lethargica appears to owe to supernormal circuit reinforcement
      during almost continuous sleep.

PMID- 15737793
TI  - Opioids for chronic nonmalignant and neuropathic pain.

PMID- 15737794
TI  - Genetics and variability in opioid response.
AB  - The human genome project has revealed data on genomic variation which may
      influence the pharmacological responses. In pain therapy, the genetic background
      influencing the efficacy of opioid therapy is of special interest. Screening for
      variations in expression of drug metabolizing enzymes has been suggested as a
      potential tool for improving patient therapy. CYP2D6 genetic variability is
      supposed to be a major factor of adverse drug reaction, possibly influencing
      hospital stay and total costs. Further candidate genes involved in pain
      perception, pain processing and pain management like opioid receptors,
      transporters and other targets of pharmacotherapy are under investigation.
      Aspects of genetic differences influencing efficacy, side effects and adverse
      outcome of pharmacotherapy will be of importance for future pain management.

PMID- 15737795
TI  - Opioid analgesia in the newborn.
AB  - Pain in neonates is now well established. Studies of the developmental
      neurobiology of pain have revealed that pain processing in the immature is very
      different from that in the mature nervous system. Neonates undergo considerable
      maturation of peripheral, spinal and supraspinal afferent pain transmission over
      the early postnatal period but are able to respond to tissue injury with specific
      behaviour and with autonomic, hormonal and metabolic signs of stress and
      distress. Opioid analgesia is now widely used in neonates. There is evidence that
      morphine requirements may be low in the youngest patients. Sensory threshold
      testing in rat pups has shown that the analgesic potency of systemic morphine
      mechanical stimulation is significantly greater in the neonate and declines with
      postnatal age. The changing morphine sensitivity in the postnatal period may be
      part of a general reorganisation in the structure and function of primary
      afferent synapses, neurotransmitter/receptor expression and function and
      excitatory and inhibitory modulation from higher brain centres. Importantly
      opioid receptor expression undergoes significant developmental regulation - mu
      opioid receptors, observed to be exuberantly expressed in the neonatal rat, have
      been found to be functional. These findings have important implications for the
      human neonate as they provide a possible explanation for the differences in
      morphine requirements observed in the youngest patients. The study of the
      underlying mechanisms of pain and analgesia in development has enabled important
      changes in clinical practice. However, pain in the newborn remains poorly
      understood and continued research and intensive study in this area is essential
      for further effective analgesic intervention and the discovery of new targets for
      therapy.

PMID- 15737796
TI  - Involvement of cytokines, chemokines and adhesion molecules in opioid analgesia.
AB  - Tissue destruction is accompanied by an inflammatory reaction. The inflammatory
      reaction leads to activation of nociceptors and the sensation of pain. Several
      mediators are responsible for pain and hyperalgesia in inflammation including
      cytokines, chemokines, nerve growth factor as well as bradykinin, prostaglandins
      and ATP. Simulatenously however, analgesic mediators are secreted: opioid
      peptides, somatostatin, endocannabinoids and certain cytokines. Opioid peptides
      secreted from immune cells are so far the best studied peptides in peripheral
      inflammatory pain control. This system is hampered for example by anti-adhesion
      molecule treatment. Novel immunosuppressive drugs for treatment of autoimmune
      disease targetting cytokines, chemokines or adhesion molecules should therefore
      be evaluated for potential harmful effects on pain.

PMID- 15737797
TI  - Opioids in neuropathic pain: clues from animal studies.
AB  - For many years the clinical consensus was that opioids were ineffective in
      neuropathic pain. However this view is changing and here we discuss the
      mechanisms of opioid analgesia in terms of the changes that can occur in
      preclinical models of nerve injury. We argue that opioid mechanisms can be
      perturbed by neuropathy but in most cases these negative influences can be
      overcome by dose-escalation.

PMID- 15737798
TI  - What to learn from in vivo opioidergic brain imaging?
AB  - Ligand-PET studies are attracting increasing interest in experimental and
      clinical research. As the most elaborated of PET techniques, ligand-PET allows
      the demonstration of receptor distributions, and thus, the delineation of
      neurochemical pathologies in the disease state. Recent developments are promising
      that ligand-PET will even allow to characterize dynamic and short-term changes in
      neurotransmission and will tremendously add to the understanding of
      neurophysiology on the receptor level. In pain studies, mainly the mu-opioidergic
      agonist [(11)C]-carfentanil and the unspecific opioid receptor antagonist [(11)C]
      diprenorphine are applied. Utilizing these ligands the thalamus, prefrontal and
      cingulate cortex, basal ganglia and midbrain structures have been shown to
      possess high amounts of opioidergic receptors in vivo and it is well accepted,
      that the receptor density is higher in projections of the medial than those of
      the lateral pain system. Changes in receptor availability were observed in
      patients suffering from chronic pain. Rheumatoid arthritis, trigeminal neuralgia
      and central poststroke pain (CPSP) all lead to decreased ligand binding in pain
      processing regions during the painful period in comparison to pain free intervals
      or healthy subjects. These decreases may either be the consequence of increased
      endogenous release or indicate receptor internalization/down-regulation or loss
      of neurons carrying these receptors. Recent studies also evidenced [(11)C]
      carfentanil binding changes due to acute experimental pain. One possible
      interpretation of these changes is that the PET-ligand might be displaced by
      endogenous opioidergic ligands. One major region, where this "ligand
      displacement" was observed, was the thalamus. These findings highlight the
      importance of the opioidergic system in pain processing and the power of ligand
      PET to advance the understanding of pain.

PMID- 15737799
TI  - Intravenous opioid testing in patients with chronic non-cancer pain.
AB  - The clinical use of an intravenous opioid testing can help to predict whether
      opioids will be beneficial. The determination of individual opioid responsiveness
      justifies subsequent long-term opioid treatment and is generally recommended. An
      overview over current testing procedures is given with particular regard to
      choice of opioid, maximum dose, determination of endpoints and duration of
      testing and recovery. Remifentanil testing is a new approch and is studied in a
      randomized placebo-controlled cross-over study in 24 patients suffering from
      severe non-cancer pain. An ascending infusion of remifentanil and placebo
      respectively was titrated against endpoints. The testing allowed a disctinction
      between 11 opioid-responders and 13 non-responders. Complete recovery after end
      of infusion was rapid with a reach of baseline conditions after 25 min in all
      patients. Thus the complete remifentanil testing procedure required at utmost 1
      h. In conclusion, remifentanil testing offers a more rapid procedure allowing the
      routine use in an ambulatory setting.

PMID- 15737801
TI  - Improving opioid effectiveness: from ideas to evidence.
AB  - Opioid effectiveness can be improved by individualizing dosing, route of
      administration and the drug. Particularly in the treatment of chronic non-cancer
      pain, careful patient selection is essential. The current review concentrates on
      new ideas about improving opioid effectiveness by increasing efficacy or reducing
      adverse effects by combining other drugs that modulate opioid receptor mediated
      effects. These pharmacological "oipioid adjuvants" include e.g. alpha(2)
      adrenergic agonists, non-steroidal anti-flammatory analgesics, NMDA-receptor
      antagonists, CCK-antagonists, gabapentinoids and NK-1 receptor antagonists. The
      theoretical background and the clinical evidence of these combinations will be
      discussed.

PMID- 15737800
TI  - Opioids in chronic non-cancer pain, indications and controversies.
AB  - The use of opioid analgesics for long term management of chronic non-cancer pain
      is now an accepted, although still a controversial medical practice. In some well
      selected patients with long-lasting or recurrent pain, severe enough to markedly
      reduce their quality of life, and for whom no other more effective and less risky
      therapy is available, opioid analgesics may reduce intensity of pain, increase
      functioning and improve quality of life for prolonged periods. The type of pain
      and pain history of the patients do not predict reliably the chance of long term
      success or risk of complications from opioid therapy. However, the outlook for
      successful long term opioid therapy is better in a patient with a stable
      psychosocial situation having nociceptive type pain that is markedly relieved by
      a moderate dose of a long lasting oral or transdermal opioid, than a patient from
      a complex and unstable psychosocial background having neuropathic type pain that
      is relieved only partly by a higher dose of a potent opioid. When a patient is
      managed by a multidisciplinary team, the compliance is better and risk of loss of
      control and complications are less than when a single doctor is managing the
      patient. The evidence base for this type of pain management is meagre because the
      needed randomized controlled trials, which ideally should last for several years,
      have not been performed. Therefore a number of national and international
      guidelines are being published, recommending experts' opinion on appropriate use
      and responsible follow-up of long term treatment with opioids for chronic non
      cancer pain.

PMID- 15737802
TI  - Opioid use in the elderly.
AB  - Pain treatment in the elderly is an important challenge to Western societies due
      to increasing numbers of old persons, their higher incidence of pain, and their
      greater susceptibility to adverse effects of pain medication. We provide an
      overview of the factors liable to influence opioid action in the elderly
      population. A major challenge for the physician prescribing opioids in the
      elderly is their greater risk of medication-associated problems. Thus, older
      patients suffer increased vulnerability to adverse drug effects and interactions,
      higher rates of polypharmacy, and more comorbidity. These problems are compounded
      by a relative lack of definitive published information. There is clearly a need
      for more research in this area. Aging affects opioid pharmacokinetics via altered
      body composition (distribution volumes) and organ function (liver=metabolism,
      kidney=excretion). Pharmacodynamics is affected via impaired
      neurotransmitter/peptide production and changed receptor affinities/populations.
      Older women may need less morphine analgesia postoperatively, while pain
      sensitivity tends to increase particularly in older men. However, the net effects
      of changes in opioid pharmacology with age on clinical opioid analgesia remain
      unclear, probably due to the significantly greater variability in body function
      with increasing age. Practical recommendations for opioid prescription in the
      elderly include meticulous review of indication for opioid use, not only
      initially but also at regular intervals thereafter. A policy of careful titration
      should be followed, with conservative choice of dosage on starting. Dosing
      intervals may need to be lengthened subsequently. Finally, it should be
      remembered that old persons do not necessarily need less opioid than younger
      ones.

PMID- 15737803
TI  - Opioid medication and driving ability.
AB  - In many European countries the use of opioids for long-term treatment of
      nonmalignant pain has dramatically increased during the last decade in order to
      improve the patient's quality of life, to allow an active social life and the
      return to work. In modern society, driving is regarded as an essential activity
      of daily living. Since opioids are centrally acting drugs that may interfere with
      the ability of safely driving a motor vehicle, the question arises of whether or
      not and on which conditions patients under continuous opioid medication may be
      considered fit to drive. In this article the evidence from recent studies of
      opioid effects on driving ability of patients is reviewed. Based on these data,
      the prerequisites and restrictions for driving under chronic opioid medication
      are outlined and practical guidelines are proposed.

PMID- 15737804
TI  - Opioids and central sensitisation: I. Preemptive analgesia.
AB  - Opioids are powerful analgesics when used to treat acute pain and some forms of
      chronic pain. A large body of literature has shown that opioids can, in addition,
      also prevent (this review) or induce and perhaps reverse, some forms central
      sensitisation in in vitro and in vivo animal models of pain. However, the concept
      of central sensitisation is, at present, ambiguous and the usefulness of opioids
      as preemptive analgesics in human pain patients is still not clear.

PMID- 15737805
TI  - Opioids and central sensitisation: II. Induction and reversal of hyperalgesia.
AB  - Opioids are powerful analgesics when used to treat acute pain and some forms of
      chronic pain. In addition, opioids can preempt some forms of central
      sensitization. Here we review evidence that opioids may also induce and perhaps
      reverse some forms of central sensitization.

PMID- 15737806
TI  - Can opioids prevent post-operative chronic pain?
AB  - Chronic post-operative pain is a major source of suffering and disability. Better
      standardisation for assessing and reporting chronic post-operative pain is
      needed. Peripheral and central nervous plasticity seem to play a major role in
      the development of chronic post-injury pain. Complex mechanisms, including
      several receptor systems and messenger systems are involved. Thus, it is unlikely
      that one single agent will solve the problem. Opioids have proven effect both in
      animal models, experimental human models, and in some clinical models. Timing and
      dose seem to be of importance. However, it is likely that polypharmacy and multi
      modal treatment is necessary to further improve the preventive strategy.

PMID- 15737807
TI  - Opioid tolerance and dependence -- do they matter?
AB  - The use of opioids has long been accepted as the standard of care in patients
      with cancer and acute pain. Opioids can further be used effectively in specific
      subgroups of patients with chronic nonmalignant pain states. While the
      development of tolerance and physical dependence are known effects of opioids in
      cancer and noncancer pain populations, these patients can not be regarded as
      addicted. However, long-term therapy with short-acting opioids predisposes to
      tolerance and addiction. Recent research has confirmed the important role of
      psychopathologic and psychosocial conditions as predictors of failed opioid
      effectiveness in a significant number of noncancer pain subgroups. The clinical
      picture of failed therapy may be complicated by noncompliance, concealed
      consumption of psychotropic substances, and diversion of prescribed opioids for
      various purposes as, e.g., selling for profit, or sharing excess opioids with
      others. This article discusses the effects of opioid therapy, including
      tolerance, physical dependence, drug-aberrant behavior, drug history,
      psychopathology, and somatization.

PMID- 15737808
TI  - Imaging of acute versus pathological pain in humans.
AB  - Pain subserves different functions. Acute pain from the intact body alerts the
      victim to immediately react and withdraw from the bodily threat, ideally before
      an injury happens. However, during manifest injury and tissue inflammation,
      withdrawal and flight are no longer adaptive. Instead, sparing the affected body
      part to promote healing requires heightened awareness and avoidance behaviour
      over longer periods of time. Quality and time scales of behavioural adaptations
      are therefore substantially different between pain during normal compared to
      abnormal tissue states. Given these functional differences we postulated that the
      two phenomena also recruit different forebrain systems. We used positron emission
      tomography (PET) and subtracted scans obtained during painful heating of normal
      skin from scans during equally intense but normally non-painful heating of
      capsaicin-treated skin. This comparison reveals the specific activation of a
      medial thalamic pathway to limbic forebrain structures such as anterior insula,
      perigenual anterior cingulate, ventral striatum, and prefrontal cortex during
      pain originating in the chemically sensitised skin. It is possible that the
      unique forebrain recruitment by pain under a patho-physiological tissue status is
      caused by a significantly greater facilitation of the multi-synaptic projections
      from the spino-parabrachial tract of the superficial dorsal horn to the medial
      thalamus compared to deeper and direct lateral thalamic projections from the
      spino-thalamic tract.

PMID- 15737809
TI  - Use of the Rydel-Seiffer graduated tuning fork in the assessment of vibration
      threshold in postherpetic neuralgia patients and healthy controls.
AB  - BACKGROUND AND AIMS: Afferent large fibre impairment has been reported as a
      useful predictor of postherpetic neuralgia (PHN) in patients with acute herpes
      zoster infection, using an electromechanical device to provide quantitative
      vibrametry. We aimed to demonstrate a clinically significant increase in
      vibration threshold in individuals with PHN compared to age-matched controls,
      using the portable and affordable Rydel-Seiffer graduated tuning fork. METHODS:
      We studied 45 PHN subjects aged over 55 years, and 45 age-matched controls with
      no history of herpes zoster infection. We excluded subjects with a history of
      disorders associated with neuropathy or immunocompromise. Measurements were
      performed at the ulnar styloid process and the head of the first metatarsal on
      the right side, in a warm room with the subject seated. Readings were taken in
      triplicate and the data analysed by a repeated measures design. RESULTS: We
      observed a significant difference in vibration threshold at both wrist and toe
      between the PHN and control groups (p < 0.001). Age-stratification of subjects
      produced an increased and clinically useful difference between the two groups at
      both sites in subjects between 55 and 70 years (p < 0.0001). CONCLUSIONS: We have
      shown a statistically significant decrease in vibration sensitivity in
      individuals with PHN aged 55-70 years compared to age-matched healthy controls,
      using the Rydel-Seiffer graduated tuning fork. A prospective study of patients
      with acute zoster infection is needed to determine the sensitivity and
      specificity of the graduated tuning fork in predicting PHN in patients with acute
      zoster infection.

PMID- 15737810
TI  - Health care providers' orientations towards common low back pain predict
      perceived harmfulness of physical activities and recommendations regarding return
      to normal activity.
AB  - The Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT)
      differentiates between a biomedical versus a biopsychosocial treatment
      orientation with regard to common low back pain. This study re-examined the
      factor structure and psychometric properties of the PABS-PT, along with the
      relationship between PABS-PT scores and the perceived harmfulness of physical
      activities and treatment recommendations for common low back pain. Two hundred
      and ninety-seven paramedical therapists completed the PABS-PT and questionnaires
      measuring related concepts, rated the perceived harmfulness of 41 daily physical
      activities depicted in photographs and gave recommendations for return to normal
      activity for three patients with low back pain. Analysis revealed two factors
      labelled 'biomedical' and 'biopsychosocial treatment orientation'. Furthermore,
      scores on both factors of the PABS-PT were related to measures of related
      concepts (statistically significant Pearson correlation coefficients between 0.30
      and 0.65) such as the HC-PAIRS and a therapist version of the TSK. Regression
      analyses revealed that both factors were consistent predictors of judgements of
      the harmfulness of physical activities (PHODA) and of recommendations for return
      to work and normal activity.

PMID- 15737811
TI  - Brain processing of tonic muscle pain induced by infusion of hypertonic saline.
AB  - Most of the previous studies on the effects of pain on Regional Cerebral Blood
      Flow (rCBF) had been done with brief cutaneous or intramuscular painful stimuli.
      The aim of the present study was to investigate the effect on rCBF of long
      lasting tonic experimental muscle pain. To this end we performed PET
      investigations of rCBF following tonic experimental low back pain induced by
      continuous intramuscular infusion of hypertonic (5%) saline (HS) with computer
      controlled infusion pump into the right erector spinae on L(3) level in 19
      healthy volunteers. Changes in rCBF were measured with the use of (15)O labelled
      water during four conditions: Baseline (before start of infusion), Early Pain (4
      min after start of infusion), Late Pain (20 min after start of infusion) and Post
      Pain (>15 min after stop of infusion) conditions. Results of SPM analysis showed
      relative rCBF increase in the right insula and bilateral decrease in the temporo
      parieto-occipital cortex during initial phase of painful stimulation (Early Pain)
      followed by activation of the medial prefrontal region and bilateral inhibition
      of insula, anterior cingulate and dorso-lateral prefrontal cortex mainly in
      ipsilateral hemisphere during Late Pain conditions. The results show that longer
      lasting tonic experimental muscle pain elicited by i.m infusion of HS results in
      decreases rather than increases in rCBF. Possible explanations for differences
      found in rCBF during tonic hypertonic saline-induced experimental muscle pain as
      compared with previous findings are discussed.

PMID- 15737812
TI  - Breakthrough pain in malignant and non-malignant diseases: a review of
      prevalence, characteristics and mechanisms.
AB  - Breakthrough pain or transient worsening of pain in patients with an ongoing
      steady pain is a well known feature in cancer pain patients, but it is also seen
      in non-malignant pain conditions with involvement of nerves, muscles, bones or
      viscera. Continuous and intermittent pain seems to be a general feature of these
      different pain conditions, and this raises the possibility of one or several
      common mechanisms underlying breakthrough pain in malignant and non-malignant
      disorders. Although the mechanisms of spontaneous ongoing pain and intermittent
      flares of pain (BTP) may be difficult to separate, we suggest that peripheral
      and/or central sensitization (hyperexcitability) may play a major role in many
      causes of BTP. Mechanical stimuli (e.g. micro-fractures) changes in chemical
      environments and release of tumour growth factors may initiate sensitization both
      peripherally and centrally. It is suggested that sensitization could be the
      common denominator of BTP in malignant and non-malignant pain.

PMID- 15737813
TI  - Testing the sequential model of pain processing in irritable bowel syndrome: a
      structural equation modeling analysis.
AB  - Pain, the cardinal feature of irritable bowel syndrome (IBS), is a
      multidimensional phenomenon with sensory and affective dimensions. Price's pain
      processing model was used to delineate four a priori sequentially related stages
      (pain sensation intensity, immediate pain unpleasantness, long-term suffering,
      and pain-related behavior). Although prior research with both healthy individuals
      and somatic pain patients supports the model in general, its applicability to IBS
      is unclear. Our goal was to extend the scope of the sequential model and test its
      fundamental tenets using structural equation modeling (SEM) with data obtained
      from 168 Rome II diagnosed IBS patients (19% male, 81% female). A secondary goal
      was to assess the relationship between a set of contextual factors associated
      with IBS (age, gender, trait anxiety) and the four pain stages. Results were
      consistent with a successive order of pain processing such that the pain
      sensation directly impacts pain unpleasantness, which, in turn, leads to
      suffering and illness behaviors. However, contrary to a model with strictly
      successive stages, pain sensation had independent effects on illness behaviors
      over and above pain affect. The effect of anxiety on illness behavior was
      mediated by suffering, while psychopathology directly influenced pain sensation
      and pain unpleasantness but not later stages. Age was related to pain sensation
      and illness behaviors but not pain affect. Gender tended to be more strongly
      associated with more distal pain stages (e.g., pain affect) vis-a-vis its effects
      on pain sensation. These data are generally supportive of a four-stage pain
      processing model.

PMID- 15737814
TI  - The relationship between somatic and emotional stimuli: a comparison between
      adolescents with temporomandibular disorders (TMD) and a control group.
AB  - The overall purpose of this study was to determine whether adolescents with
      chronic temporomandibular disorder (TMD) pain are more sensitive to all types of
      somatic and emotional stimuli compared with a matched healthy control group.
      Sixty adolescents, 8 boys and 52 girls ranging from 12 to 18 years, participated
      in the study. Thirty of the subjects exhibited TMD, reporting pain of at least 3
      months duration. The age- and gender-matched control group consisted of 30 dental
      recall patients who reported TMD pain less than once a week. All participants
      completed a 40-item questionnaire comprising 10 items each of pleasant and
      aversive qualities crossed with somatic and emotional forms of stimuli. The
      items, a selection of a broad range of familiar stimuli by a panel of experts,
      were rated based on intensity of experience (0-10, numerical rating scale). Well
      fitting items that formed a valid construct within each of the four domains were
      selected using Rasch analysis. The results showed that adolescents with TMD pain
      reported significantly greater sensitivity (p<0.05) to aversive somatic and
      pleasant somatic stimuli than the controls. The differences between groups for
      the aversive emotional and pleasant emotional stimuli were non-significant. These
      findings suggest that chronic TMD pain states in adolescents are accompanied by
      amplification of bodily, but not purely emotional stimuli and that cognitive
      systems are implicated, not only an alteration of the nociceptive systems.

PMID- 15737815
TI  - Cognitive development: at the crossroads?

PMID- 15737816
TI  - Methodological challenges for understanding cognitive development in infants.
AB  - Studies of cognitive development in human infants have relied almost entirely on
      descriptive data at the behavioral level - the age at which a particular ability
      emerges. The underlying mechanisms of cognitive development remain largely
      unknown, despite attempts to correlate behavioral states with brain states. We
      argue that research on cognitive development must focus on theories of learning,
      and that these theories must reveal both the computational principles and the set
      of constraints that underlie developmental change. We discuss four specific
      issues in infant learning that gain renewed importance in light of this opinion.

PMID- 15737817
TI  - Influencing brain networks: implications for education.
AB  - In our view, a central issue in relating brain development to education is
      whether classroom interventions can alter neural networks related to cognition in
      ways that generalize beyond the specific domain of instruction. This issue
      depends upon understanding how neural networks develop under the influence of
      genes and experience. Imaging studies have revealed common networks underlying
      many important tasks undertaken at school, such as reading and number skills, and
      we are beginning to learn how genes and experience work together to shape the
      development of these networks. The results obtained appear sufficient to propose
      research-based interventions that could prove useful in improving the ability of
      children to adjust to the school setting and to acquire skills like literacy and
      numeracy.

PMID- 15737818
TI  - Imaging the developing brain: what have we learned about cognitive development?
AB  - The human brain undergoes significant changes in both its structural architecture
      and functional organization across the life span. Advances in neuroimaging
      techniques over the past decade have allowed us to track these changes safely in
      the human in vivo. We review the imaging literature on the neurobiology of
      cognitive development, focusing specifically on cognitive task-dependent changes
      observed in brain physiology and anatomy across childhood and adolescence. The
      findings suggest that cortical function becomes fine-tuned with development.
      Brain regions associated with more basic functions such as sensory and motor
      processes mature first, followed by association areas involved in top-down
      control of behavior.

PMID- 15737819
TI  - Connectionist models of cognitive development: where next?
AB  - Over the past two decades, connectionist models have generated a lively debate
      regarding the underlying mechanisms of cognitive development. This debate has in
      turn led to important empirical research that might not have occurred otherwise.
      More recently, advances in developmental neuroscience present a new set of
      challenges for modelers. In this article, I review some of the insights that have
      come from modeling work, focusing on (1) explanations for the shape of change;
      (2) new views on how knowledge may be represented; (3) the richness of
      experience. The article concludes by considering some of the new challenges and
      opportunities for modeling cognitive development.

PMID- 15737820
TI  - Species comparative studies and cognitive development.
AB  - The comparative study of infant development and animal cognition brings to
      cognitive science the promise of insights into the nature and origins of
      cognitive skills. In this article, I review a recent wave of comparative studies
      conducted with similar methodologies and similar theoretical frameworks on how
      two core components of human cognition--object permanence and gaze following-
      develop in different species. These comparative findings call for an integration
      of current competing accounts of developmental change. They further suggest that
      evolution has produced developmental devices capable at the same time of
      preserving core adaptive components, and opening themselves up to further
      adaptive change, not only in interaction with the external environment, but also
      in interaction with other co-developing cognitive systems.

PMID- 15737821
TI  - The dawn of cognitive genetics? Crucial developmental caveats.
AB  - Attempts to bridge genetics and cognition are rapidly coming to the forefront of
      cognitive neuroscience. It is therefore crucial to evaluate the current state of
      knowledge about disorders of known genetic origin as a way of assessing whether,
      and if so how, links between genotype and cognitive phenotype can be drawn,
      however indirect these links might be. We review recent empirical findings from
      research on genetic disorders at three levels of description--cognitive, neural
      systems, and cellular--that caution against simple genotype-phenotype mappings at
      all levels. Most importantly, interdisciplinary efforts to integrate human
      genetics and cognition will need to operationalize the mechanisms driving both
      typical and atypical developmental processes over time.

PMID- 15737822
TI  - Cognitive development following early brain injury: evidence for neural
      adaptation.
AB  - Over the past few decades a large body of work from developmental neurobiology
      has shown that mammalian brain development is the product of dynamic and adaptive
      processes operating within highly constrained, but continually changing,
      biological and environmental contexts. The recent study of children with prenatal
      focal brain injury supports this dynamic view of development for humans.
      Children's injuries often affect substantial portions of one cerebral hemisphere,
      resulting in damage that would compromise cognitive ability in adults. However,
      longitudinal behavioral studies of this population have revealed only mild
      deficits. It is suggested here that children's capacity for adaptation reflects
      normal developmental processes operating against a backdrop of serious neural
      perturbation. Data from three behavioral domains--linguistics, spatial cognition
      and affective development--illustrate this complex profile of change.

PMID- 15737824
TI  - Processes of change in brain and cognitive development.
AB  - We review recent advances in the understanding of the mechanisms of change that
      underlie cognitive development. We begin by describing error-driven, self
      organizing and constructivist learning systems. These powerful mechanisms can be
      constrained by intrinsic factors, other brain systems and/or the physical and
      social environment of the developing child. The results of constrained learning
      are representations that themselves are transformed during development. One type
      of transformation involves the increasing specialization and localization of
      representations, resulting in a neurocognitive system with more dissociated
      streams of processing with complementary computational functions. In human
      development, integration between such streams of processing might occur through
      the mediation of language.

PMID- 15737825
TI  - Are clinical trials finally growing up?

PMID- 15737826
TI  - Partial mastectomy: a balance between oncology and aesthetics?

PMID- 15737823
TI  - Missing sights: consequences for visual cognitive development.
AB  - The effects of early-onset blindness on the development of the visual system have
      been explained traditionally by the stabilization of transient connections
      through Hebbian competition. Although many of the findings from congenital
      cataract and congenital blindness are consistent with that view, there is
      inconsistent evidence from studies of visual cognition in children treated for
      visual deprivation from cataract, case reports of recovery of vision in adults,
      and studies of visual reorganization after late-onset blindness. Collectively,
      the data from congenital cataract and congenital blindness indicate that early
      visual experience sets up the infrastructure for later learning involving both
      the dorsal ("where") and ventral ("what") streams. Nevertheless, there is
      surprising residual plasticity in adulthood that can be revealed if vision is
      lost either temporarily or permanently. This has important implications for
      understanding the role of early visual experience in shaping visual cognitive
      development.

PMID- 15737827
TI  - Complementary treatment: who cares how it works, as long as it does?

PMID- 15737829
TI  - Prevention of malignant spinal-cord compression.

PMID- 15737830
TI  - China's plans to curb cervical cancer.

PMID- 15737831
TI  - Oncoplastic approaches to partial mastectomy: an overview of volume-displacement
      techniques.
AB  - Oncoplastic surgery refers to several surgical techniques by which segments of
      malignant breast tissue are removed to achieve wide surgical margins while the
      remaining glandular tissue is transposed to achieve the best possible cosmetic
      outcome. We summarise the general approach to oncoplastic lumpectomy for surgeons
      who recognise the limitations of standard lumpectomy for large breast cancers,
      and review different cancer distributions in the breast and their associated
      imaging characteristics. Full-thickness fibroglandular excision of the mass and
      surrounding breast tissue allows resection with wide surgical margins. Subsequent
      breast-flap advancement (mastopexy) results in closure of the resulting surgical
      defect with good or excellent cosmetic closure. These approaches can improve both
      the aesthetic outcome of breast cancer resections and the likelihood of surgeons
      obtaining wide surgical margins in preparation for breast-conserving
      radiotherapy. Advanced volume-displacement techniques, which are based on the key
      principles of breast reductive surgery, can greatly increase the options for
      breast conservation in complex cancer cases.

PMID- 15737832
TI  - Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in
      cancer biology and treatment.
AB  - Thymidine phosphorylase (TP) is often induced in the tumour microenvironment by
      physiological and chemical stress. Its induction protects cells from apoptosis
      and helps cell survival by stimulating nucleoside metabolism and angiogenesis.
      Chemotherapy often upregulates TP, which acts in cell rescue; this result
      indicates that TP is a crucial therapeutic target. Clinical trials for metastatic
      diseases have shown that TP-targeting chemotherapy with fluorouracil derivatives
      greatly improves the effectiveness of conventional chemotherapy for not only
      response but also prognosis. This new idea, the improvement of TP-inducible
      therapy with TP-targeting therapy, should be further investigated for early
      disease states, and inhibitors of TP warrant extensive investigation.

PMID- 15737833
TI  - MRI in treatment of adult gliomas.
AB  - Diffuse astrocytomas of the adult cerebral hemispheres are unique among tumours
      in human beings in the extent to which their imaging features are related to
      histopathological characteristics and clinical behaviour. However, understanding
      is still restricted about the value of imaging features in the measurement of
      response and of progression in these tumours. The present approach used in
      clinical trials, which consists of an anatomical measurement of the enhancing
      tumour on MRI, has many problems, and might not be acceptable as a surrogate
      endpoint for survival in patients with glioblastoma who are enrolled in clinical
      trials. Dynamic imaging techniques, such as capillary permeability mapping, are
      being used in studies of new drugs that target specific molecular features of
      gliomas; however, the validity of these techniques has not been elucidated.
      Diffusion imaging can be valuable for fibre-tract mapping to assist surgical
      planning and might become useful in measuring early response to treatment in
      densely cellular tumours. Functional imaging techniques can be used to localise
      motor, sensory, and language-control areas before surgery. Intraoperative MRI has
      produced improvements in the extent of tumour resection, and molecular imaging is
      another technique on the horizon, which could come to have a role in clinical
      trials in the near future. Thus, as a rapidly expanding sphere of investigation,
      brain-tumour imaging is producing great excitement. The aim of these new
      techniques is to aid the identification of more effective treatments.

PMID- 15737834
TI  - Chemotherapy and anaesthetic drugs: too little is known.
AB  - A growing number of patients undergo surgical procedures with general anaesthesia
      soon after receiving chemotherapy; occasionally such treatment can be given
      during surgery. Therefore, it is worthwhile and prudent to consider the
      pharmacological interactions between anticancer and anaesthetic drugs. We review
      published data on the pharmacological interactions between antineoplastic and
      anaesthetic drugs, despite the fact that this specific topic is poorly
      represented in published work. This low coverage seems to be due more to a lack
      of knowledge and understanding rather than an absence of interactions between the
      two drug types. Since the number of individuals receiving chemotherapy in the
      perioperative period is rising, patients who might have potentially dangerous and
      unwanted effects are also due to increase in number. Thus, we should be vigilant
      in the careful surveillance of these interactions as well as broaden our
      knowledge of in-vivo and in-vitro findings and investigations. Classic cytostatic
      compounds and modern drugs should be extensively studied, and new anticancer
      therapies closely interacting with immunological responses need to be better
      understood, since their clinical effectiveness might be modified by anaesthetics
      that are currently used. More frequently, tumours are being managed in a
      multimodal integrated approach with medical, surgical, and radiotherapeutic
      aspects.

PMID- 15737835
TI  - Preoperative gemcitabine for unresectable, solid pseudopapillary tumour of the
      pancreas.

PMID- 15737836
TI  - Relapse of primary extranodal marginal-zone B-cell lymphoma of the dura mater.

PMID- 15737837
TI  - Imaging bronchial carcinoma in situ: possible roles for combined positron
      emission tomography (PET)-CT.

PMID- 15737839
TI  - Days 2 and 3 of the dawn of modern military surgery: the sequel to Senn.

PMID- 15737840
TI  - "Modern" military surgery: 19th century compared with 20th century.

PMID- 15737841
TI  - Breast cancer patients with pN0(i+) and pN1(mi) sentinel nodes have high rate of
      nonsentinel node metastases.
AB  - BACKGROUND: The recent American Joint Committee on Cancer revision of the staging
      system for breast cancer classifies sentinel node metastases < 0.2 mm (pN0[i+])
      as node negative and those > 0.2 mm but < 2 mm are designated pN1(mi). We
      examined the association between size of sentinel node metastases and rate of
      nonsentinel node metastases, specifically in the subgroup of patients with
      micrometastases. STUDY DESIGN: We examined the nonsentinel nodes of 124 patients
      with positive sentinel nodes and correlated the likelihood of nonsentinel node
      involvement with the size of the metastasis in the sentinel node and primary
      tumor characteristics. RESULTS: Nonsentinel node metastases were found in 19% (6
      of 31) of patients with sentinel node metastases <or= 0.2 mm, 20% (6 of 30) of
      patients with metastases 0.2 mm to 2 mm, and 46% (29 of 63) of patients with
      metastases > 2 mm. Multivariate analysis found that involvement of the majority
      of sentinel nodes (p = 0.01) and sentinel metastases > 2 mm (p = 0.001) were
      significantly related to presence of metastases in nonsentinel nodes. Age, tumor
      size, pathology, multifocality, satellites, and lymphovascular invasion were not
      significantly related to nonsentinel node metastases in multivariate analysis.
      CONCLUSIONS: These findings indicate that frequency of nonsentinel node
      metastases with sentinel node metastases <or= 0.2 mm is comparable to the
      frequency when sentinel metastases are > 0.2 to 2 mm. Omitting complete axillary
      dissection in pN1(mi) and pN0(i+) patients may leave residual disease in up to
      20% of these patients.

PMID- 15737842
TI  - Ductal carcinoma in situ of the breast and heparanase-1 expression: a molecular
      explanation for more aggressive subtypes.
AB  - BACKGROUND: Ductal carcinoma in situ of the breast (DCIS) forms a heterogeneous
      group of lesions with varying invasive potential. This study tested whether
      heparanase-1 (HPR1), an endoglycosidase that specifically degrades the heparan
      sulfate (HS) proteoglycans in the breast extracellular matrix, was associated
      with the most aggressive DCIS subtypes. STUDY DESIGN: Fifty-seven DCIS specimens
      and 10 normal breast specimens were examined for HPR1 expression using
      immunohistochemical staining. Twenty-seven arbitrarily selected specimens were
      also examined for HS deposition by immunofluorescence staining, confirming HPR1
      activity. Patient medical records were obtained to explore a possible association
      between biologic potential using Van Nuys Prognostic Index (VNPI) and HPR1
      expression. RESULTS: Twenty-one (75%) of 28 comedo and microinvasive DCIS
      specimens stained HPR1 positive; 4 (14%) of 29 other subtypes (papillary,
      cribriform, and solid subtypes) stained HPR1 positive on immunohistochemistry (p
      = 0.003). Among 27 DCIS stained for HS, we found that 8 (67%) of 12 HPR1-negative
      DCIS had intact HS deposition in the extracellular basement membrane; none of the
      15 HPR1-positive DCIS stained HS positive. Six (86%) of seven DCIS with VNPI
      scores 8 to 9 and 14 (50%) of 28 DCIS with VNPI scores 5 to 7 were HPR1 positive;
      only 3 (17%) of 18 DCIS with VNPI scores 3 to 4 were HPR1 positive. Median VNPI
      score in patients with HPR1-positive DCIS was 7 (range 3 to 9), compared with 4.5
      (range 3 to 7) in patients with HPR1-negative DCIS (p < 0.001). CONCLUSIONS: HPR1
      was expressed at a significantly higher frequency in the invasive comedo and DCIS
      with microinvasion subtypes than in the noninvasive subtypes. HPR1 expression was
      inversely associated with HS deposition in the extracellular basement membrane of
      the DCIS. HPR1 expression was associated with a higher VNPI score. These
      observations suggest that HPR1 expression in DCIS can play an important role in
      development of DCIS into an invasive breast cancer.

PMID- 15737843
TI  - Downregulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gene expression after
      neoadjuvant three-modality treatment in patients with esophageal cancer.
AB  - BACKGROUND: To find out if neoadjuvant therapy could alter tumor response
      determinants that might affect tumor sensitivity to the treatment, we
      investigated intratumoral expressions of genes associated with chemosensitivity,
      radiosensitivity, or both before and after radiochemotherapy. STUDY DESIGN:
      Twenty-four patients with locally advanced, resectable esophageal cancer (cT2
      4,Nx,M0) received neoadjuvant 5-FU/cisplatin/36 Gy treatment followed by
      transthoracic en bloc esophagectomy. Expression levels of thymidylate synthase,
      dihydropyrimidine dehydrogenase, excision repair cross-complementing gene 1 ,
      glutathione S-transferase Pi, epidermal growth factor receptor, and HER2 were
      measured in matched preradiochemotherapy endoscopic tumor biopsies and in
      postradiochemotherapy resection specimens. mRNA was isolated from formalin-fixed,
      paraffin-embedded, laser microdissected tumor tissues, and a quantitative
      fluorescent dye real-time reverse transcription polymerase chain reaction system
      was used for gene expression measurement. RESULTS: There was a significant
      reduction in the expression levels of thymidylate synthase (p < 0.01),
      dihydropyrimidine dehydrogenase (p = 0.03), excision repair cross-complementing
      gene 1 (p < 0.01), glutathione S-transferase Pi (p = 0.03), HER2 (p < 0.01), and
      epidermal growth factor receptor (p = 0.04). The change in the levels of
      epidermal growth factor receptor mRNA in post- compared with pretreatment
      specimens was significantly associated with the histopathologic grade of
      regression (p = 0.01). CONCLUSIONS: The expression levels of a set of genes that
      are possible determinants of 5-FU/cisplatin/radiation therapy antitumor activity
      are significantly downregulated by neoadjuvant radiochemotherapy in esophageal
      cancer.

PMID- 15737844
TI  - Caudate hepatectomy for cancer: a single institution experience with 150
      patients.
AB  - BACKGROUND: Resection of the caudate lobe of the liver is technically demanding,
      with the disparate goals of preserving major vascular and biliary structures
      without compromising tumor clearance. Our objective was to assess our results
      with resection of the caudate lobe of the liver for malignant disease. STUDY
      DESIGN: From 1992 to 2004, we performed caudate resection for malignancy in 150
      patients. Clinicopathologic correlates, surgical methods, patterns of recurrence,
      and survival were analyzed. RESULTS: Of the 150 patients identified, 21 (14%)
      underwent an isolated caudate lobe resection and 129 (86%) underwent caudate lobe
      resection as part of a more extensive hepatectomy. The most common indication was
      for metastatic colorectal cancer (48%), followed by cholangiocarcinoma (30%) and
      hepatocellular cancer (10%). Thirty patients required resection and
      reconstruction of the portal vein (n = 16), vena cava (n = 15), or both.
      Pathologic microscopic margins were positive in 30 patients (20%). At least one
      postoperative complication was reported in the majority of patients (55%), and
      nine patients (6%) died as a result of these complications. Postoperative
      mortality was significantly higher in patients who underwent a major vascular
      reconstruction (20% versus 2.5%, p < 0.002). Median survivals for patients with
      colorectal metastasis, cholangiocarcinoma, and hepatocellular carcinoma were 37,
      28, and 32 months, respectively. CONCLUSIONS: Performing caudate hepatectomy with
      negative microscopic margins remains a technical challenge because of the
      proximity of major biliary and vascular structures. Although caudate resection of
      the liver can be performed safely, concomitant major vascular reconstruction
      substantially increases the mortality of the procedure.

PMID- 15737845
TI  - Transaminitis after pancreatic islet transplantation.
AB  - BACKGROUND: An asymptomatic, self-limited transaminitis uniformly follows
      pancreatic islet transplantation (PIT) performed through portal vein (PV)
      infusion. The underlying cause and significance of this transaminitis is unclear.
      STUDY DESIGN: Records of all patients with insulin-dependent diabetes mellitus
      who had undergone PIT at our institution were reviewed. All PITs were performed
      in conjunction with a remote pancreatic islet isolation center and done through
      percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels,
      serum glucose concentrations, insulin requirements, and color-flow Doppler
      ultrasonography examinations of the right upper quadrant were assessed before and
      after PIT. RESULTS: Eleven patients have undergone a total of 26 PITs. An
      elevated ALT level occurred in all 11 patients (100%) after the first PIT, with
      the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less
      frequent and less marked after the second PIT. A negative correlation between
      viability of the pancreatic islets transplanted (r = -0.44, p = 0.03) and a
      positive correlation between the ratio of maximum to initial PV pressure (r =
      0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler
      ultrasonography examinations showed no occurrences of PV thrombosis or
      intrahepatic hematoma. Finally, the degree of transaminitis did not correlate
      with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot
      be used to measure allograft rejection or function. CONCLUSIONS: Transaminitis
      after PIT is common and self-limited. Post-PIT transaminitis does not signal
      acute rejection or serious procedure-related complications such as PV thrombosis
      or intrahepatic hematoma.

PMID- 15737846
TI  - Detection of B-RAF and N-RAS mutations in human melanoma.
AB  - BACKGROUND: It is now known that activating point mutations in components of the
      mitogen-activated protein kinase pathway commonly occur in melanoma. We
      previously described a method to detect point mutations in heterogenous tissues
      containing both wild-type and mutant B-RAF and N-RAS genes by using site-directed
      mutagenesis to introduce new restrictions sites in the cDNA sequence when the
      specific point mutations are present. We modified this technique to improve
      sensitivity and used it to determine the incidence of B-RAF and N-RAS mutations
      in human melanoma. STUDY DESIGN: We screened 115 melanoma samples for the most
      common B-RAF and N-RAS mutations found in melanoma using a site-directed
      mutagenesis-based detection technique. Southern blotting was used to increase
      sensitivity of the basic system. We also tested this method of genetic mutation
      detection in fine-needle aspiration specimens and paraffin-embedded tissues.
      RESULTS: Sixty-eight samples (20 of 36 primaries, 18 of 27 regional metastases,
      16 of 40 nodal metastases, and 9 of 12 distant metastases) harbored the V599E B
      RAF mutation (59%), 17 contained a Q61R N-RAS mutation, and 4 contained a Q61K N
      RAS mutation. We were able to detect the V599E mutation in genomic DNA from
      paraffin-embedded melanoma samples and could routinely detect this mutation in
      fine-needle aspirations of melanoma tumors. This method of detection was
      sensitive and specific with no false positives. CONCLUSIONS: Activating mutations
      of B-RAF and N-RAS were present in approximately 60% and 18%, respectively, of
      samples tested. The site-directed mutagenesis system of mutation detection was
      both sensitive and specific in detecting these mutations and will likely prove
      very clinically useful in future studies.

PMID- 15737847
TI  - Increased expression of Cyr61 (CCN1) identified in peritoneal metastases from
      human pancreatic cancer.
AB  - BACKGROUND: Identification of extracellular matrix proteins (ECM) associated with
      tumor cell metastasis may generate targets for future therapy against pancreatic
      cancer metastases. We hypothesized that comparison of ECM-associated gene
      expression in primary and metastatic pancreatic tumors would identify ECM
      proteins associated with pancreatic metastasis. STUDY DESIGN: A clinically
      relevant model of pancreatic cancer was used to generate RNA from primary and
      metastatic tumors; it was evaluated by microarray analysis with subsequent
      cluster analysis. Target genes (Cyr61 and integrins alpha(v) and beta(3))
      identified by microarray analysis were confirmed by reverse transcription
      polymerase chain reaction and immunohistochemistry analysis. RESULTS: Peritoneal
      metastases at sites distant from the primary tumor were present in all animals
      bearing orthotopic tumors. High-density microarray comparison of gene expression
      in metastases versus primary pancreatic tumors identified a greater than twofold
      increase in the expression of Cyr61, a secreted matricellular protein that binds
      to integrins. Reverse transcription polymerase chain reaction confirmed the
      microarray results, and immunohistochemistry analysis demonstrated increased
      Cyr61 protein and persistent alpha(v)beta(3) expression in peritioneal
      metastases. Additionally, immunohistochemistry demonstrated increased
      collocalization of Cyr61 and alpha(v) in metastases relative to primary tumor.
      CONCLUSIONS: The ECM protein Cyr61 shows increased expression in metastatic
      lesions in a clinically relevant model of pancreatic adenocarcinoma. Protein
      analysis confirms the microarray results and collocalization of Cyr61, and
      alpha(v) suggests that interaction between Cyr61 and alpha(v)beta(3) promotes
      formation of peritoneal metastases.

PMID- 15737848
TI  - A model for predicting outcomes in patients with differentiated thyroid cancer
      and model performance in comparison with other classification systems.
AB  - BACKGROUND: This study was performed to determine the prognostic factors for
      differentiated thyroid cancer, and to establish a mathematical prognostic model.
      STUDY DESIGN: A retrospective study was conducted in 347 differentiated thyroid
      cancer patients. Univariate and multivariate prognostic factor analyses were
      carried out using the Kaplan-Meier and Cox regression methods. RESULTS: Without
      adjustment for treatment in the multivariate analysis, age, tumor size,
      angioinvasion, and distant metastasis were significant predictors of outcomes.
      The very low-risk, low-risk, high-risk, and very high-risk groups were identified
      from the logistic regression equation. Overall and event-free survival
      estimations at 10 years were 100% and 100% for very low-risk patients, 88% and
      75% for low-risk patients, 30% and 16% for high-risk patients, and 5% and 0% for
      very high-risk patients. Inclusion of treatment in the multivariate analysis
      showed, in addition to other variables, that both total or near total
      thyroidectomy (versus thyroidectomy less than total and near total thyroidectomy,
      p = 0.0002; hazard ratio, 0.4; 95% CI, 0.3-0.7) and adjuvant radioactive iodine
      treatment (versus no treatment with radioactive iodine, p = 0.0001; hazard ratio,
      0.5; 95% CI, 0.2-0.8) were associated with a reduced hazard of death in the
      followup period. By subgroup analysis, total and near total thyroidectomy, along
      with radioactive iodine, appeared to provide a survival benefit for all patients
      except those in the very low-risk group. CONCLUSIONS: The proposed mathematical
      model is satisfactory for predicting outcomes. Total and near total thyroidectomy
      along with radioactive iodine treatment might provide a survival advantage for
      differentiated thyroid cancer, except for those with very low risk.

PMID- 15737849
TI  - A randomized, double-blind, placebo-controlled trial to determine effectiveness
      of antibiotic prophylaxis for tension-free mesh herniorrhaphy.
AB  - BACKGROUND: In recent years, use of prosthetic material for inguinal hernia
      repair has increased dramatically. Tension-free repairs have gained popularity
      not only for recurrent or complicated hernias, but for primary hernia repairs as
      well. Although routine use of prophylactic antibiotics is not recommended in the
      Philippines for open nonimplant herniorrhaphy, there is little direct clinical
      evidence on which to base recommendations when implantable mesh is used. STUDY
      DESIGN: We conducted a prospective, randomized, double-blind, placebo-controlled
      trial comparing wound infection rates in 360 patients (180 received prophylactic
      antibiotics, 180 received a placebo) undergoing primary inguinal hernia repair
      electively using polypropylene mesh. Age, gender, American Society of
      Anesthesiologists class, type of hernia, type of anesthesia, and duration of
      operation were recorded. Infections were evaluated 1 week, 2 weeks, and 1 month
      after operation by an independent surgeon. All complications were recorded.
      Results were assessed using chi-square, Fisher's exact test, and Student's t
      tests as appropriate. RESULTS: Groups were well matched for all preoperative
      variables studied, including comorbid conditions. Six patients from the
      antibiotic group and four from the placebo group failed to followup after the
      second week. Superficial surgical site infection developed in 3 patients (1.7%)
      from the antibiotic group and 6 (3.3%) from the placebo group (p = 0.50). One
      from each group developed deep surgical site infection. Both patients were
      readmitted and underwent repeated debridement, which eventually resulted in graft
      loss. CONCLUSIONS: Preoperative administration of single-dose antibiotic for
      tension-free inguinal mesh herniorrhaphy did not markedly decrease risk of wound
      infection in this patient population. Our results do not support use of
      antibiotic prophylaxis for tension-free mesh herniorrhaphy.

PMID- 15737852
TI  - What's new in plastic and maxillofacial surgery.

PMID- 15737853
TI  - What's new in general surgery: transplantation.

PMID- 15737854
TI  - Scientific evidence for application of topical hemostats, tissue glues, and
      sealants in hepatobiliary surgery.

PMID- 15737855
TI  - The cardiovascular protective effect of red wine.

PMID- 15737856
TI  - Influence of gender on surgical outcomes: does gender really matter?

PMID- 15737858
TI  - Part 3: surgical palliation of advanced illness: what's new, what's helpful.

PMID- 15737859
TI  - Three-dimensional volumetric analysis for reconstruction of middle hepatic vein
      tributaries in living donor liver transplantation.

PMID- 15737860
TI  - Cavernous hemangioma presenting as Budd-Chiari syndrome.

PMID- 15737861
TI  - Laparoscopic liver resection.

PMID- 15737863
TI  - Assessing a regional trauma system.

PMID- 15737864
TI  - Impact of gastric bypass on survival.

PMID- 15737866
TI  - Current issues in transfusion medicine in Norway.
AB  - Important current issues in transfusion medicine in Norway are discussed. Current
      patient legislation specifically defines blood donors as patients, and blood and
      blood products are defined as drugs. Donor selection is controversial, especially
      deferral of all persons born in, or having lived for more than one year in areas
      with high prevalence of infections that are transmitted by blood. The threshold
      for becoming a blood donor is high, but registered donors donate frequently, e.g.
      2,4 whole blood donations per year on average. Some blood banks have specialized
      in multicomponent aphereis technology, in particular collection of two units of
      red cells.

PMID- 15737867
TI  - Survival of renal allografts from living donors and the importance of being the
      mother of the organ donor.

PMID- 15737868
TI  - Hemovigilance in Norway.

PMID- 15737869
TI  - Lymphoma--the immune system in disarray Theme for the 11th Congress of the South
      African Lymphoma Study Group meeting.

PMID- 15737870
TI  - The South African bone marrow registry (SABMR) in 2004.
AB  - Because of the presence of rare HLA antigens, particularly in patients of African
      ancestry, the SABMR was established in 1991. Currently approximately 20% of
      unique HLA types in the international database is from the SABMR. The SABMR
      donors now total approximately 45,000. Sixty-five South African patients have
      received matched unrelated donor transplants, 20 (30%) with a local donor. Most
      donors are from Caucasian background. To increase the genetic diversity of the
      SABMR donor pool, the policy is now to enrol more black and mixed ancestry
      donors.

PMID- 15737871
TI  - Perspectives of the management of childhood lymphoma: experience at Tygerberg
      Hospital, Western Cape, South Africa.
AB  - Hodgkin's disease (HD) in children corresponds to a large degree to HD in adults.
      Non-Hodgkin's Lymphoma (NHL) in children, however, differs from NHL in adults
      with respect to the classification, natural history, management and course. For
      practical reasons clinicians generally classify and treat NHL in children as
      either B-cell or T-cell disease. Over the past 22 years, the Paediatric Oncology
      Unit of the Tygerberg Hospital has treated HD with three different regimens. Use
      of the CLVPP and MOPP/ABVD regimens resulted in late relapses that adversely
      affected event free survival (EFS). For the last four years HD has been treated
      according to the regimen suggested by Schellong with good short term survival
      rates. Lymphoblastic or T-cell NHL is treated with regimens normally used for
      acute lymphoblastic leukaemia (e.g. BFM protocols) or modified leukaemia
      treatments for leukaemia-lymphoma syndromes (e.g. LSA2L2). We lately use a
      modified BFM regimen with a 70% EFS for all stages. Three consecutive regimens
      have been used to treat B-cell NHL over the past 22 years. The first was a COMP
      regimen, followed by the LMB-89 and LMB-96 regimens. Although toxicity has
      increased with the increased intensity of the treatment regimen, EFS has improved
      from 25% to 87% for all B-cell NHL. The majority of patients had stage III and IV
      disease. Although the LMB regimens are toxic, the implementation is manageable
      provided good laboratory back up and supportive facilities are available.

PMID- 15737874
TI  - Hemopoietic chimerism following stem cell transplantation.
AB  - Hematopoietic chimerism is a measure of the number of donor and recipient cells
      in the host following stem cell transplantation (SCT). The type of conditioning
      therapy prior to SCT has a major impact on the chimeric status in the recipient.
      Different techniques of measurement have varying sensitivities. The use of
      polymerase chain reaction (PCR) of short tandem repeats (STR) using fluorescent
      amplification permits quantification using Genescan analysis. When SCT is used
      for malignant haematological disorders, measurement of chimeric status may
      indicate early relapse and in aplastic anemia graft rejection. Reduced intensity
      or T-cell depletion is associated with mixed haemopoietic chimerism. SCT for
      benign haematological disorders does not require complete donor chimerism for a
      successful outcome.

PMID- 15737873
TI  - Autologous and allogeneic stem cell transplantation in follicular lymphoma.
AB  - Follicular non-Hodgkin's lymphomas (NHL) usually present in advanced stage and
      although frequently are chemotherapy-sensitive remain incurable using
      conventional approaches. Treatment options are evolving rapidly and now include
      targeted therapies such as monoclonal antibodies. Recent studies, including the
      EBMTR-sponsored "CUP Trial" (conventional Chemotherapy, Unpurged autograft,
      Purged autograft), demonstrate that for patients under age 60 years with
      recurrent chemotherapy-sensitive disease, autologous stem cell transplantation
      (ASCT) provides a survival benefit over conventional therapy. Allogeneic stem
      cell transplantation (alloSCT) has become a more effective option. Although
      incorporation of TBI into the preparative regimen may increase treatment-related
      mortality (TRM), relapses appear to be reduced compared to a chemotherapy-alone
      regimen. Reduced-intensity alloSCT procedures now are being performed at an
      increasing rate, in part due to a lower risk for TRM. Until more data are
      available, however, reduced-intensity alloSCT should be considered only in cases
      where myeloablative conditioning is contra-indicated. There are no clear means
      for choosing ASCT versus alloSCT, a decision influenced by amount of residual
      tumor, disease-responsiveness, degree of marrow involvement and extent of prior
      chemotherapy. ASCT or alloSCT in first remission remains an investigational
      procedure. Future considerations include incorporation of novel preparative
      regimens, in vitro purging techinques, anti-lymphoma vaccines, post-transplant
      immunotherapy and ex vivo-manipulated donor lymphocyte infusions.

PMID- 15737872
TI  - Therapy of chronic lymphocytic leukemia with purine analogs and monoclonal
      antibodies.
AB  - B-cell chronic lymphocytic leukemia (CLL) is a clonal hematopoietic disorder
      characterized by proliferation and accumulation of small lymphocytes. It is the
      most common form of leukemia in North America and Europe. The management of CLL
      is determined by the stage and activity of the disease. Several randomized
      studies indicate that cytotoxic therapy based on alkylating agents in the
      indolent phase of disease, does not prolong the survival time of CLL patients.
      Chlorambucil, with or without steroids, has been for many years the drug of
      choice in previously untreated patients with this leukemia. Alternative treatment
      approaches, including new purine nucleoside analogs (PNA), such as fludarabine
      and 2-chlorodeoxyadenosine (cladribine) have also shown activity in CLL. The
      randomized studies have indicated a higher overall response, complete remission
      rates and longer response duration in patients treated initially with PNA than
      with chlorambucil or cyclophosphamide based combination regimens. These agents
      alone or in combinations, seem to be the treatment of choice for patients failing
      standard therapies. The monoclonal antibodies directed against CD52 antigen
      (alemtuzumab, Campath-1H) and CD20 antigen (rituximab) demonstrate also
      significant activity in CLL patients. These agents have significant single-agent
      activity, distinct mechanism of action and generally, favorable toxicity
      profiles. Both antibodies achieved the most promising results in the treatment of
      patients with relapsed or refractory CLL. More recently the effect of alemtuzumab
      in previously untreated patients has been also investigated and results are very
      encouraging. A multicenter prospective randomized study comparing alemtuzumab and
      chlorambucil as first line therapies are ongoing and preliminary results show
      acceptable toxicity profile of monoclonal antibody.

PMID- 15737875
TI  - Mobilization and collection of peripheral blood progenitor cells for
      transplantation.
AB  - Bone marrow transplantation gradually expanded as a treatment modality for
      various malignant and non malignant disease conditions. Since the discoveries of
      the potential of Peripheral Blood Progenitor Cells (PBPC) in the hematopoietic
      reconstitution mid 1980s and early 1990s PBPC gradually replaced bone marrow as
      the preferred source of stem cells. The introduction of hematopoietic cytokines
      that can mobilize large number of progenitors into circulation accelerated PBPC
      usage. Technological advancements in the apheresis instrumentation greatly helped
      in the conversion from marrow to PBPC. PBPC collection is less painful, less
      expensive and transplant with PBPC results in faster hematological recovery than
      with marrow. Almost all of the autologous transplants are currently performed
      with PBPC and a similar trend is seen with the allogeneic transplants. The
      progenitor cell mobilization regimen for autologous patients can be cytokines
      alone or cytokines combined with chemotherapy. In the majority of the patients
      the required minimal cell dose of 2.5-5.0 x 10(6)/kg CD34+ cells can be collected
      in one or two apheresis collections. A few of autologous transplant patients who
      mobilize poorly require several collections. Allogeneic donors are generally
      mobilized with daily subcutaneous injections of G-CSF 10 microg/kg for 5 days.
      The PBPC are collected in one or two apheresis procedures. The side effects of G
      CSF are generally mild to moderate; however rare serious reactions including
      rupture of the spleen have been reported. The collection of PBPC in pediatric
      patients poses additional challenges yet an adequate dose of cells can be
      collected with the available apheresis instrumentation. The apheresis collection
      procedures are safe with no serious adverse consequences. Future scientific
      advancements may expand the use of PBPC for other clinical application in
      addition to the current use for hematological reconstitution.

PMID- 15737876
TI  - Outcome following alemtuzumab (CAMPATH-1H)-containing reduced intensity
      allogeneic transplant regimen for relapsed and refractory non-Hodgkin's lymphoma
      (NHL).
AB  - We report the outcome following RIT for NHL in 88 patients (LG-NHL n = 41, HG-NHL
      n = 37, MCL n = 10). Thirty-seven had received prior autografts and 21 were in CR
      at transplant. Conditioning was with alemtuzumab, fludarabine and melphalan.
      Sixty-five patients received PBSC from HLA-identical siblings and 23 received BM
      from matched unrelated donors. GVHD prophylaxis was with cyclosporin A. Grade III
      IV acute GVHD developed in 4 patients and chronic GVHD in 6 patients. With a
      median follow-up of 36 months (range 18-60), the actuarial overall survival (OS)
      at 3 years was 34% for HG-NHL, 60% for MCL and 73% for LG-NHL (p < or = 0.001).
      The 100-day and 3-year TRM for patients with LG-NHL were 2% and 11%,
      respectively, and were better (p = 0.01) than for patients with HG-NHL (27% and
      38%, respectively). The actuarial current progression free survival (PFS) at 3
      years, including those who achieved remission following DLI for progression, was
      65% for LG-NHL 50% for MCL and 34% for HG-NHL (p = 0.002). Twenty-one patients
      received DLI for MRD, persistent disease or relapse and 15 received DLI for mixed
      hematopoietic chimerism. Patients with relapsed LG-NHL and CLL achieve excellent
      PFS with extremely low TRM and GVHD, even when matched family donors are
      unavailable.

PMID- 15737877
TI  - Chronic lymphocytic leukemia: a review of some new aspects of the biology,
      factors influencing prognosis and therapeutic options.
AB  - This review provides some basic information on chronic lymphocytic leukemia (CLL)
      and attempts to present some of the newer data which have accumulated in recent
      years including those relating to familial aggregation of CLL and the detection
      of monoclonal CD5+ lymphocytosis in the general population and families of CLL
      patients. Novel data on the pathogenesis and concepts of cell origin in CLL are
      also reviewed stressing the fact that there is biased IgVH gene usage, and the
      importance of mutational status of the CLL cell, as reported in recent years by
      different authors. A brief review of the significance of the microenvironmental
      interactions between stromal cells and other accessory cells, and the leukemic
      CLL cells is also provided. Other clinical aspects are discussed including
      diagnostic criteria, clinical staging, and the newer prognostic factors which
      influence survival and timing of therapy for CLL patients. We also attempt to
      outline the therapeutic options available and the principles of planning risk and
      age-adapted treatment, stressing the importance and the necessity for
      participating in ongoing and future international clinical trials.

PMID- 15737879
TI  - The effect of peptide stimulation on haematopoietic stem cell mobilisation
      including engraftment characteristics and a note on donor side effects.
AB  - Aplasia or irreversible bone marrow failure and a variety of haematologic
      malignancies, as well as an increasing number of solid tumours, currently include
      various forms of marrow or equivalent transplantation in routine management. In
      both allogeneic and autologous procedures stable recipient immunohaematopoietic
      reconstitution depends upon infusing the requisite population harvested at a
      precise time following commencement of a stimulatory peptide. In a first step
      this prospective study documented the safety of apheresis, defined side effects
      and enumerated mononuclear, CD34+ and CD3+ cells obtained. In the second stage
      delivery of the graft, characterised in this way and with the additional
      measurement of in vitro growth in clonogenic assay, to the suitably conditioned
      patient was correlated with recovery of neutrophil and platelet numbers appearing
      in the circulation. In a third and ongoing analysis the influence of passenger T
      lymphocytes is being evaluated for impact on infection and a potential anti
      tumour effect. The conclusion is that this technology is reliable, has a high
      degree of patient acceptability without untoward complications, and that local
      results correspond to international experience thereby providing an important and
      relevant measure of quality control.

PMID- 15737878
TI  - Hairy cell leukemia: survival and relapse. Long-term follow-up of purine analog
      based therapy and approach for relapsed disease.
AB  - Since its initial description approximately 50 years ago, there has been an
      impressive evolution in therapies for hairy cell leukemia. Long-term follow-up
      with 2-cholorodeoxyadenosine and 2'-deoxycoformycin demonstrates that both agents
      result in a high complete remission rate and overall survival. Relapse rates
      appear to be between 20% and 30%. Therapeutic strategies for patients with
      relapsed disease include retreatment with a purine analog, rituximab, or the anti
      CD22 pseudomonas exotoxin A immunoconjugate, BL-22.

PMID- 15737880
TI  - Estimation and predictive use of the corrected count increment--a proposed
      clinical guideline.
AB  - BACKGROUND AND OBJECTIVE: Platelets are frequently given inappropriately. The
      accepted indication is symptomatic thrombocytopaenia due to bone marrow failure.
      In contrast replacement therapy is contraindicated in immune mediated peripheral
      sequestration because it is almost always ineffective and also aggravates the
      already rapid rate of the clearance due to superimposed isoimmunisation.
      Furthermore circulating levels, rather than the clinical situation, customarily
      trigger the request and would typically be at 20 x 10(9)/l. Usage is under
      evaluated and, accordingly, current practice has been scrutinised and a guideline
      proposed that is applicable to user and vendor alike. DESIGN AND METHODOLOGY:
      Prospectively a consecutive series of eligible cases were selected and, with
      informed consent, all relevant information recorded. Specific observations were
      haematologic status, quality of the product and the impact of previous exposure
      to blood fractions on outcome. Additionally, factors that influence response were
      documented and included disseminated intravascular coagulation, splenomegaly and
      concurrent use of intravenous Amphotericin B. The absolute numbers infused, the
      increase in peripheral value recorded and this ratio which is designated as
      corrected count index generated in each instance. RESULTS: The CCI was computed
      for each of the 85 megaunits given to 29 individuals and subsequently estimated
      for the entire sample population using regression analysis. Each of the variables
      was used to test the hypothesis that such a figure might differ depending on
      patient sub-population. This approach was accurate in 60% of the time and
      predicates a more rational use of donor characteristics. The cardinal measurement
      is that supplied by the transfusion service which can be used as a basis for
      clinically important predictors of anticipated benefit. CONCLUSION: This data, in
      keeping with international practice, leads to the recommendation that commercial
      and other services routinely measure and specify absolute numbers. The
      clinicians, reciprocally, should always confirm this figure and then match
      anticipated to observed outcome. Failure to carry out these simple procedures
      lead to gross over utilisation of this expensive intervention, risks unnecessary
      sensitisation and furthers persistence with sub-optimum administration.

PMID- 15737882
TI  - Molecular control of iron metabolism.
AB  - As described in this volume, our knowledge of mammalian iron metabolism has
      advanced dramatically over the past decade. While basic physiological concepts
      were described through elegant experiments in the 1950s and 1960s, many molecular
      details remained unknown. Modern techniques in genetics, biochemistry and
      molecular biology have allowed for the identification and characterization of
      most, but probably not all, of the key molecules that move iron into, out of, and
      between cells. Insight into the complex regulation of these iron transport
      proteins has been accelerated through the identification of hemochromatosis
      disease genes. Although much of the information has been gleaned from experiments
      in animal models, it is likely that it can be directly extrapolated to humans.

PMID- 15737883
TI  - Hepcidin--a regulator of intestinal iron absorption and iron recycling by
      macrophages.
AB  - Hepcidin is a recently discovered peptide made in the liver, distributed in
      plasma and excreted in urine. This peptide hormone is the homeostatic regulator
      of intestinal iron absorption, iron recycling by macrophages, and iron
      mobilization from hepatic stores. Hepcidin acts by inhibiting the efflux of iron
      through ferroportin, the sole known iron exporter of enterocytes, macrophages and
      hepatocytes. As befits an iron-regulatory hormone, hepcidin synthesis is
      increased by iron loading and decreased by anemia and hypoxia. Hepcidin is
      markedly induced during infections and inflammation, causing iron to be
      sequestered in macrophages, hepatocytes and enterocytes. The resulting decrease
      in plasma iron levels eventually contributes to the anemia associated with
      infection and inflammation. These alterations in iron metabolism probably have a
      role in host defense by limiting the availability of iron to invading
      microorganisms. At the opposite extreme, early studies indicate that hepcidin
      deficiency--due to the dysregulation of its synthesis or mutations in the
      hepcidin gene itself--is the immediate cause of most forms of hemochromatosis.

PMID- 15737884
TI  - Modification of iron regulation by the inflammatory response.
AB  - Iron is an essential compound for immunosurveillance because of its growth
      promoting and differentiation-inducing properties for immune cells and its
      interference with cell-mediated immune effector pathways and cytokine activities.
      Thus, the reticuloendothelial system has generated sophisticated strategies to
      control iron metabolism in general and the handling of the metal within immune
      cells. Cytokines, immune-cell-derived radicals, and acute-phase proteins affect
      the regulation of iron homeostasis at different levels ranging from
      transcriptional interference with iron genes to modulation of iron transport
      capacities of transmembrane iron channels. Thus, under inflammatory conditions a
      diversion of iron traffic from the circulation to storage sites of the
      reticuloendothelial system occurs. This results in an iron-restricted
      erythropoiesis and the development of anemia, termed 'anemia of chronic disease'.
      The development of hypoferremia and hyperferritinemia under chronic inflammatory
      conditions may also harbor some positive effects: first, by limiting the
      availability of the essential nutrient and growth factor iron to invading
      microbes and tumor cells, thus blocking their proliferation, and secondly by
      strengthening cell-mediated immune effector pathways directed against invading
      pathogens. Studying iron metabolism under inflammatory conditions will extend our
      knowledge and improve our understanding of regulatory pathways in host-pathogen
      interactions during infection and cancer, and may hold the key for future
      therapeutic developments for the treatment of such diseases as well as for anemia
      of chronic disease.

PMID- 15737885
TI  - The penetrance of hereditary hemochromatosis.
AB  - Since its original description as a rare disease of iron overload resulting in
      liver disease, diabetes mellitus, and bronzing of the skin ('bronze diabetes'),
      hereditary hemochromatosis has undergone several redefinitions leading to widely
      varying estimates of its prevalence. Over the last decade, the finding of a
      relatively high prevalence of the C282Y polymorphism of the HFE gene associated
      with hemochromatosis in Northern European populations suggested that the disease
      may be much more common than previously thought. However, several large
      population-based studies have now shown that the penetrance of the C282Y/C282Y
      genotype is very low, indicating that C282Y homozygosity is a necessary but not
      sufficient factor in causation of the disease. Studies are now focusing on other
      genetic and environmental factors, including alcohol, that may contribute to
      differential expression of C282Y homozygosity.

PMID- 15737886
TI  - Role of early case detection by screening relatives of patients with HFE
      associated hereditary haemochromatosis.
AB  - Hereditary haemochromatosis is a primary inherited disorder of iron metabolism
      leading to progressive iron loading of parenchymal cells of the liver and other
      organs with diverse clinical manifestations, including cirrhosis, diabetes and
      skin pigmentation. This chapter will focus on HFE-associated hereditary
      haemochromatosis, which accounts for approximately 90% of cases in Caucasian
      populations. Penetrance is incomplete, with variable clinical expression. The
      majority of cases demonstrate biochemical expression, but a much lower proportion
      develop advanced disease. Clinical disease--especially hepatic fibrosis--is
      related to the level of body iron stores, which is reflected primarily in the
      liver. The available evidence indicates that adequate screening and diagnostic
      strategies ensure that early case detection and treatment occur prior to the
      development of irreversible end-organ damage. The most cost-effective methods of
      early case detection are family (cascade) screening and evaluation of potential
      cases by primary care physicians with a high index of clinical suspicion.

PMID- 15737887
TI  - New insights into iron homeostasis through the study of non-HFE hereditary
      haemochromatosis.
AB  - Non-HFE haemochromatosis is a negative definition applied to all those
      haemochromatosis disorders that are unrelated to HFE mutations. Four genes are
      responsible for the distinct types of non-HFE haemochromatosis: hepcidin and
      hemojuvelin are the genes involved in type 2 or juvenile haemochromatosis,
      transferrin receptor 2 is involved in type 3 haemochromatosis, and ferroportin 1
      is mutated in type 4, the atypical dominant form of primary iron overload.
      Molecular genetic studies of these conditions have greatly contributed to our
      understanding of the regulation of iron absorption. A milestone was the discovery
      that hepcidin, the key iron regulator in mice, is the gene mutated in the most
      severe, juvenile form of haemochromatosis. This finding indicates a fundamental
      role of hepcidin in inhibiting both iron absorption from duodenal cells and iron
      release from macrophages, and has opened up a new view of haemochromatosis as a
      disorder of hepcidin.

PMID- 15737888
TI  - Role of ferritin and ferroportin genes in unexplained hyperferritinaemia.
AB  - A large body of evidence indicates that the level of serum ferritin parallels the
      concentration of storage iron within the body, regardless of the cell type in
      which it is stored. Elevated serum ferritin levels, in the absence of
      inflammation and liver disease, are currently taken to indicate increased iron
      stores and require further investigation to determine the site of iron overload.
      Until recently, the only genetic disorder with elevated serum ferritin levels
      known in Western countries was hereditary HLA-related HFE-related genetic
      haemochromatosis in Caucasians (HFE, OMIM 235200), and a high serum ferritin in
      apparently healthy persons was considered suggestive of this disease. In the last
      few years, at least two novel genetic disorders of iron metabolism presenting as
      unexplained hyperferritinaemia have been recognized. The first one is hereditary
      hyperferritinaemia/cataract syndrome (HHCS, OMIM 600886). HHCS arises from
      various point mutations or deletions within a protein binding sequence in the 5'
      UTR of the L-ferritin mRNA that results in increased efficiency of L-ferritin
      translation. The second one is haemochromatosis type 4, or HFE4 (OMIM 606069), or
      ferroportin disease. In this latter condition, reticuloendothelial iron overload
      and hyperferritinaemia are caused by loss-of-function mutations in the SLC11A3
      gene that mainly impair macrophage iron recycling. These genetic disorders should
      be taken into account in the differential diagnosis of unexplained
      hyperferritinaemia.

PMID- 15737889
TI  - Neuroferritinopathy: a neurodegenerative disorder associated with L-ferritin
      mutation.
AB  - Neuroferritinopathy is a dominantly inherited movement disorder characterized by
      deposition of iron and ferritin in the brain, normal or low serum ferritin
      levels, and highly variable clinical features. The disease, also named dominant
      adult-onset basal ganglia disease, is associated with a nucleotide insertion that
      modifies the last 22 amino acids of the ferritin L-chain. A similar dominant
      movement disorder in a French family was associated with a nucleotide insertion
      that modifies the last nine amino acids of the same molecule. Both disorders show
      ferritin and iron precipitates in the basal ganglia of the brain. Here we present
      the structural aspects of the two mutations, as well studies on cellular models
      aimed at understanding the molecular basis of the disorder. The results indicate
      that the mutations affect protein folding and stability, and that the expression
      of one of the two variant ferritins increases intracellular iron availability and
      sensitivity to oxidative damage.

PMID- 15737890
TI  - LPI-labile plasma iron in iron overload.
AB  - Labile plasma iron (LPI) represents a component of non-transferrin-bound iron
      (NTBI) that is both redox-active and chelatable, capable of permeating into
      organs and inducing tissue iron overload. It appears in various types of
      hemosiderosis (transfusional and non-transfusional) and in other iron-overload
      conditions. Sustained levels of LPI could over time compromise organ (e.g. heart)
      function and patient survival. With the advent of methods for measuring LPI in
      the clinical setting, it has become possible to assess the implications of LPI in
      the management of iron overload based on regimens of iron chelation. As LPI is
      detected primarily in patients with transfusional iron overload and other forms
      of hemosiderosis, we review here regimens of iron chelation with deferrioxamine
      and deferiprone (separately or combined) in terms of their efficacy in minimizing
      daily exposure to LPI in thalassemia major and thalassemia intermedia patients.

PMID- 15737891
TI  - Iron-chelating therapy with the new oral agent ICL670 (Exjade).
AB  - Iron-chelation therapy is essential in iron-overloaded patients. The long-term
      efficacy of this approach has been demonstrated unequivocally with deferoxamine,
      which effectively controls iron concentrations, thereby limiting organ damage and
      preventing premature death. However, as deferoxamine is administered
      parenterally, poor compliance is a significant limitation to successful patient
      management. ICL670 (Exjade) is a highly efficient and selective oral iron
      chelator. The results of phase I and phase II clinical studies indicate that
      ICL670 is at least as effective as current standard therapy (deferoxamine), with
      a tolerability and safety profile suitable for chronic, once-daily
      administration. These encouraging results have provided the rationale for the
      ongoing phase III programme, and offer physicians and patients the promise of an
      oral, once-daily, iron-chelating agent for the prevention and management of iron
      overload.

PMID- 15737892
TI  - Deferiprone therapy for transfusional iron overload.
AB  - Iron chelation is needed to prevent damage to the heart, liver and endocrine
      glands from iron overload in patients with refractory anaemias who receive
      regular blood transfusions. Desferrioxamine is still the first-line drug, but
      because of its expense in many countries, and lack of compliance because of
      difficulty with administration, there is a major need for an orally active (and
      cheaper) chelating drug. Seventeen years after the first clinical trials
      deferiprone, which is orally active, has emerged as suitable for patients for
      whom desferrioxamine is, for one reason or another, inadequate. Many patients are
      successfully chelated at a dose of deferiprone 75 mg/kg/day. Some patients may
      need higher doses (up to 100 mg/kg), or combination therapy of deferiprone every
      day and desferrioxamine on several days each week. Recent data suggest that
      deferiprone may be superior to desferrioxamine at protecting the heart from iron
      overload. The side-effects of deferiprone--agranulocytosis, neutropenia,
      gastrointestinal symptoms, arthropathy, transient changes in liver enzymes, and
      zinc deficiency--are now well recognized; they result in discontinuation of the
      drug in only 5-10% of patients. Deferiprone is now licensed in 43 countries for
      thalassaemia major patients for whom desferrioxamine is inadequate. If results of
      current trials confirm its superiority at reducing cardiac damage, it may well
      become the first-line drug for many patients.

PMID- 15737893
TI  - Diagnosis and management of iron-deficiency anaemia.
AB  - Anaemia is typically the first clue to iron deficiency, but an isolated
      haemoglobin measurement has both low specificity and low sensitivity. The latter
      can be improved by including measures of iron-deficient erythropoiesis such as
      the transferrin iron saturation, mean corpuscular haemoglobin concentration,
      erythrocyte zinc protoporphyrin, percentage of hypochromic erythrocytes or
      reticulocyte haemoglobin concentration. However, the changes in these
      measurements with iron deficiency are indistinguishable from those seen in
      patients with the anaemia of chronic disease. The optimal diagnostic approach is
      to measure the serum ferritin as an index of iron stores and the serum
      transferrin receptor as a index of tissue iron deficiency. The treatment of iron
      deficiency should always be initiated with oral iron. When this fails because of
      large blood losses, iron malabsorption, or intolerance to oral iron, parenteral
      iron can be given using iron dextran, iron gluconate or iron sucrose.

PMID- 15737894
TI  - The impact of iron fortification on nutritional anaemia.
AB  - Iron deficiency continues to be the most prevalent nutritional deficiency
      disorder in the world, affecting an estimated two billion people, most of whom
      live in developing countries. It has far-reaching effects on the health, well
      being and productivity of those affected. Iron fortification of food is regarded
      as the most cost-effective method for reducing the prevalence of nutritional iron
      deficiency. In industrialized countries this has had an important beneficial
      effect; however, nutritional anaemia remains very prevalent in developing
      countries, and iron fortification appears until recently to have had little
      impact. Two important reasons for the latter situation are inadequate
      documentation of the magnitude of the iron deficiency component of anaemia in
      different regions of the world, and the use of iron compounds that are poorly
      bioavailable in fortification programmes. Several recent interventions using
      innovative approaches to dietary fortification that ensure the delivery of
      adequate quantities of bioavailable iron have demonstrated that iron
      fortification of food can be an effective and implementable strategy for
      controlling nutritional iron deficiency in non-industrialized countries.

PMID- 15737895
TI  - Iron requirements in erythropoietin therapy.
AB  - When erythropoietin (epoetins or darbepoetin) is used to treat the anemias of
      chronic renal failure, cancer chemotherapy, inflammatory bowel diseases, HIV
      infection and rheumatoid arthritis, functional iron deficiency rapidly ensues
      unless individuals are iron-overloaded from prior transfusions. Therefore, iron
      therapy is essential when using erythropoietin to maximize erythropoiesis by
      avoiding absolute and functional iron deficiency. Body iron stores (800-1200 mg)
      are best maintained by providing this much iron intravenously in a year, or more
      if blood loss is significant (in hemodialysis patients this can be 1-3 g). There
      is no ideal method for monitoring iron therapy, but serum ferritin and
      transferrin iron saturation are the most common tests. Iron deficiency is also
      detected by measuring the percentage of hypochromic red blood cells, content of
      hemoglobin in reticulocytes, soluble transferrin receptor levels, and free
      erythrocyte protoporphyrin values, but iron overload is not monitored by these
      tests. Iron gluconate and iron sucrose are the safest intravenous medications.

PMID- 15737896
TI  - Gastropathic sideropenia.
AB  - There has been an increasing awareness recently of subtle, non-bleeding
      gastrointestinal conditions that may result in abnormal iron absorption leading
      to iron-deficiency anaemia (IDA) in the absence of gastrointestinal symptoms.
      Thus, the importance of coeliac disease as a possible cause of IDA refractory to
      oral iron treatment, without other manifestations of malabsorption syndrome, is
      increasingly being recognized. In addition, Helicobacter pylori has been
      implicated in several recent studies as a cause of IDA refractory to oral iron
      treatment, and the anaemia responds favourably to H. pylori eradication.
      Likewise, achlorhydric gastric atrophy or atrophic body gastritis (ABG), a
      condition associated with chronic idiopathic iron deficiency, has been shown to
      be responsible for refractory IDA in over 20% of patients with no evidence of
      gastrointestinal blood loss. It has also been suggested that H. pylori gastritis
      may represent an early phase of ABG in which infection may trigger an autoimmune
      process directed against gastric parietal cells by means of antigenic mimicry. In
      this review we examine in a critical manner the role of H. pylori gastritis in
      the causation of IDA, the role of ABG in the pathogenesis of iron malabsorption,
      the evidence supporting a possible cause-and-effect relationship between H.
      pylori gastritis and ABG, and the implications of these findings for the
      diagnostic work-up and management of IDA.

PMID- 15737897
TI  - Point: brachytherapy versus intensity-modulated radiation therapy in the
      management of base of tongue cancers.

PMID- 15737898
TI  - Counterpoint: brachytherapy versus intensity-modulated radiation therapy in the
      management of base of tongue cancers.

PMID- 15737901
TI  - CT-guided multi-catheter insertion technique for partial breast brachytherapy:
      reliable target coverage and dose homogeneity.
AB  - PURPOSE: To evaluate the feasibility and dosimetric reliability of a CT-guided
      method of catheter insertion for accelerated partial breast brachytherapy (APBB).
      MATERIALS AND METHODS: From 1995 to 2002, 77 patients were treated with APBB
      using a multi-catheter low-dose-rate or high-dose-rate approach. Within that
      timeframe, 29 patients with early stage invasive breast cancer were treated with
      high-dose-rate partial breast brachytherapy and had CT scans of the brachytherapy
      implant available for analysis. Initially, catheter insertion was accomplished in
      the operating room at the time of lumpectomy using standard free-hand insertion
      techniques under fluoroscopic guidance and subsequent orthogonal film dosimetry.
      To improve the efficiency and quality of the technique, the procedure was moved
      to the departmental CT-simulation suite where the catheters were placed with CT
      guidance. Basic guidelines of needle insertion and implant construction were
      followed to assure appropriate intercatheter and interplanar spacing that allowed
      optimal dosimetric coverage of the target volume. Target volumes were delineated
      and a treatment plan generated using a 3D planning system (Varian Brachyvision).
      PTV 1 cm was defined as the lumpectomy cavity plus 1 cm and PTV 2 cm as the
      lumpectomy cavity plus 2 cm. Target coverage goals were set as delivery of 100%
      of the prescribed dose to >95% of PTV 1 cm and >90% of the dose to >90% of PTV 2
      cm. Dose homogeneity index (DHI) was defined as (V150%-V100%/V100%) with a goal
      of achieving >0.75. Fifteen patients were treated using the initial method and 14
      patients using the CT-guided technique. Targets were retrospectively entered in
      the initial group and dose volume histogram analysis completed on all patients.
      The ability of each technique to achieve the target coverage and homogeneity
      goals was compared. RESULTS: With the change from traditional techniques to a CT
      guided technique, the percentage of patients satisfying all dosimetric goals
      increased from 42% to 93%. Mean dose coverage (defined as the percentage of PTV 2
      cm receiving 90% of the prescribed dose) increased from 89% to 95% (p=0.007) and
      the mean DHI increased from 0.77 to 0.82 with the new technique (p < 0.005).
      CONCLUSIONS: Reproducible target coverage and dose homogeneity were achieved with
      CT-guided catheter insertion and 3D planning software. Catheters can be optimally
      placed with intraoperative CT evaluation and 3D planning software allows improved
      implant visualization resulting in optimized dosimetry. Improvements in target
      coverage and DHI may translate into optimized local control and improved cosmesis
      with a corresponding reduction in the risk of complications.

PMID- 15737902
TI  - A hybrid approach to reducing computed tomography metal artifacts in
      intracavitary brachytherapy.
AB  - PURPOSE: To develop a hybrid approach to reduce computed tomography (CT) metal
      artifacts caused by the Fletcher-Suit applicator. METHODS AND MATERIALS: Using
      the acquired raw projection data, the hybrid algorithm determines the separate
      contributions from the metal and non-metal objects. Next, reconstructions of
      metal and non-metal images are separately obtained from their estimated
      projections. A final image is formed by appropriately combining the individual
      images. Phantom and patient data are used to evaluate the performance of this
      method. RESULTS: CT images reconstructed by use of the standard filtered
      backprojection (FBP) algorithm contain significant artifacts even for small metal
      objects. However, images reconstructed using the hybrid algorithm contain
      virtually no artifacts. For metal objects with complex structures, the hybrid
      algorithm can also yield images containing fewer severe streak artifacts than
      those reconstructed using the FBP algorithm alone. CONCLUSIONS: These studies
      demonstrate that the hybrid approach can effectively reduce CT metal artifacts
      caused by the Fletcher-Suit applicator.

PMID- 15737903
TI  - Brachytherapy management of the retroverted uterus using ultrasound-guided
      implant applicator placement.
AB  - PURPOSE: Patients with a retroverted uterus present a dilemma for brachytherapy
      in gynecologic malignancies because of the challenges of the procedure and the
      risk of uterine perforation. The purpose of this study was to evaluate the
      efficacy and outcome of ultrasound-guided brachytherapy applicator placement and
      intraoperative uterine anteversion in patients with gynecologic malignancies, who
      have a retroverted uterus. METHODS AND MATERIALS: Thirty-three brachytherapy
      insertions were performed in 18 patients with retroverted uterus (cervical
      cancer, 17; vaginal cancer, 1). The endocervical canal was dilated, the
      intrauterine Fletcher tandem was inserted in retroverted fashion and then
      anteverted along with the uterus under continuous ultrasound guidance. The
      anteverted tandem position was secured with vaginal packing and use of a second
      and/or third flange on the tandem stem. Treatment was delivered with low-dose
      rate brachytherapy using afterloading with 137Cs. Brachytherapy was combined with
      external beam radiation in all patients. Median post-therapy follow-up was 2.17
      years (range, 0.75-9.25 years). RESULTS: Procedure. Ultrasound-guided dilation of
      the cervix was achieved in all procedures. Sounding of the retroverted uterus up
      to the fundus was accomplished successfully in all but one procedure (because
      severe retroflexion of the uterus and fixation of the fundus to the sacrum).
      Ultrasound-guided anteversion of the inserted tandem and uterus was achieved in
      all procedures. No ultrasonographic evidence of perforation was seen in any of
      the procedures. Intraoperative radiographs showed satisfactory position of the
      applicators in 31 of the 33 procedures; 2 cases were re-packed resulting in
      acceptable final applicator position. No backward rotation of the tandem was
      observed over the duration of the low-dose-rate brachytherapy application. The
      mean ratio between the dose to the rectum and Point A was 73%; the ratio between
      the dose to the bladder and Point A was 76%. Outcome. In the 17 patients with
      cervical cancer, 2-year pelvic tumor control rate was 100%, and 2-year actuarial
      disease-free survival was 73%. The patient with vaginal cancer has no evidence of
      disease 5 months post-therapy. There was one complication (1/18 patients, 5.5%):
      a rectal stricture in a patient with stage IVA cervical cancer requiring
      colostomy. CONCLUSIONS: The use of ultrasound-guided uterine anteversion for
      brachytherapy applicator placement is feasible and results in acceptable outcome
      and complication rates in a population otherwise difficult to manage and at high
      risk for uterine perforation. Based on these results, this method is likely
      preferable to brachytherapy with a retroverted tandem, or to the omission of
      brachytherapy.

PMID- 15737904
TI  - A pilot trial of high-dose-rate intraoperative radiation therapy for malignant
      pleural mesothelioma.
AB  - PURPOSE: To report results of a phase II trial of high-dose-rate intra-operative
      radiation therapy (HDR-IORT) for malignant pleural mesothelioma (MPM). METHODS
      AND MATERIALS: Seven patients had extrapleural pneumonectomy with IORT (EPP/IORT)
      and 6 patients had pleurectomy/decortication with IORT (PD/IORT) between 1994 and
      1996. IORT was delivered with 192Ir using a customized applicator with a remote
      afterloader. A median of 3 sites were treated to a median area of 143 cm2. A dose
      of 1500 cGy was prescribed at each site, with 1000 cGy delivered to the
      mediastinum. Postoperative external beam radiation therapy (EBRT) was given 3-5
      weeks later. Median follow-up was 8 months (range, 1-84 months). RESULTS: Five
      patients developed local failure. Two-year local control and survival rates were
      35% and 23%, respectively. Mortality was 2/13 (15%), 1 from each surgical group.
      Serious complications requiring further intervention occurred in 3/6 (50%) of the
      EPP/IORT group and 1/5 (20%) of the PD/IORT group. CONCLUSIONS: HDR-IORT after
      EPP for MPM is prohibitively toxic and has been abandoned, while its use with PD
      remains in question.

PMID- 15737905
TI  - 103Pd brachytherapy versus radical prostatectomy in patients with clinically
      localized prostate cancer: a 12-year experience from a single group practice.
AB  - PURPOSE: In an effort to shed light on the continuing debate over the best
      treatment options for patients with localized prostate cancer, we present a
      retrospective review of patients from a single group community urology practice.
      METHODS AND MATERIALS: Data from 1707 patients were reviewed. These patients,
      with T1 or T2 adenocarcinoma of the prostate, were treated from 1992 to 2004 with
      either brachytherapy or radical retropubic prostatectomy (RRPP); 81% were aged
      over 65 years. Patients were classified into risk groups based on initial
      prostate-specific antigen (PSA) and Gleason score. Time to PSA-indicated
      recurrence was used as the measure of disease control and cure. RESULTS: Time to
      PSA-indicated recurrence was used as a measure of efficacy. Brachytherapy with
      103Pd exclusively and RRPP were found to provide equivalent control (<0.4 ng/mL
      for prostatectomy and <3 successive rises in PSA as defined by the American
      Society for Therapeutic Radiology and Oncology [ASTRO]) in low-risk groups (89%
      seeds vs. 94% RRPP). In intermediate (89% seeds vs. 58% RRPP) and high-risk (88%
      seeds vs. 43% RRPP) groups, brachytherapy patients had better control rates. The
      addition of external radiation, with or without luteinizing hormone-releasing
      hormone therapy, improved biochemical control rates in intermediate and high-risk
      brachytherapy groups. CONCLUSION: The results failed to show any superiority of
      prostatectomy over brachytherapy with 103Pd (TheraSeed; Theragenics Corp.,
      Buford, GA) regarding time until relapse as indicated by PSA level increase (>0.4
      ng/mL for prostatectomy and >3 successive rises in PSA as defined by ASTRO). We
      recently reviewed our techniques and improved equipment from 1995 to present and
      found major gains with both brachytherapy and surgery. Low risk brachytherapy
      resulted in 99% freedom from PSA failure while surgery showed results of 97%.
      Brachytherapy and prostatectomy should be offered without bias to all men with
      stage T1 and T2 organ-confined prostate cancer.

PMID- 15737906
TI  - The impact of radiation dose to the urethra on brachytherapy-related dysuria.
AB  - PURPOSE: To determine the effect of urethral dose on dysuria after permanent
      prostate brachytherapy. METHODS AND MATERIALS: One hundred eight patients without
      a preimplant history of a transurethral resection underwent brachytherapy on one
      of two prospective randomized trials for clinical T1c-T2c (2002 AJCC) prostate
      cancer. Urethral dose was stratified into cohorts of <150% and 150% minimum
      peripheral dose (mPD) respectively. No patient received prophylactic alpha
      blockers. The median follow-up was 27.4 months. Dysuria was defined as pain
      and/or burning on urination and was evaluated on a 0-10 scale. Normalization of
      dysuria was defined as a return to within 1 point of baseline. Dysuria surveys
      were obtained before brachytherapy and at 1, 3, 6, and 12 months after
      implantation. Clinical, treatment, and dosimetric parameters evaluated included
      urethral dose, age, preimplant International Prostate Symptom Score (I-PSS),
      ultrasound volume, hormonal status, supplemental XRT, isotope, V(100/200), D(90),
      the maximum post-implant I-PSS, and the time to I-PSS resolution. RESULTS: The
      incidence of dysuria peaked at 85% one month after brachytherapy with subsequent
      resolution over time. Radiation dose to the urethra (stratified into cohorts of
      <150%, and 150% mPD) was not a significant predictor of prevalence, severity, or
      resolution of dysuria. In a multivariate analysis, isotope predicted for dysuria
      normalization while preimplant I-PSS and D(90) predicted for maximum dysuria;
      however, the area under the ROC curve and the Pearson correlation coefficient
      revealed weak correlations. CONCLUSIONS: Dysuria is common after brachytherapy,
      but typically minimal in severity. Urethral doses did not predict for either
      dysuria severity or normalization. Although preimplant I-PSS was the strongest
      predictor of maximum dysuria and isotope the best predictor for dysuria
      normalization, robust predictors for brachytherapy-related dysuria were not
      identified.

PMID- 15737907
TI  - Calibration of the photon component of 198Au stents.
AB  - PURPOSE: 198Au has promising characteristics for radioactive stent material,
      having properties as a mixed beta-particle and gamma emitter. Calibration of
      these radioactive stents is required to provide accurate clinical dosimetry.
      METHODS AND MATERIALS: We have developed an electroplating technique to
      incorporate stable gold onto stents followed by activation to 198Au in the
      University of Wisconsin nuclear reactor. The calibration method is a modification
      of the NIST traceable, in-air calibration technique for high-dose-rate (HDR)
      192Ir sources. RESULTS: The air-kerma strength of HDR and low-dose-rate (LDR)
      sources was measured for proof of principle and found to agree to within 3% of
      values obtained with other NIST traceable calibration techniques. The photon
      component of two 198Au radioactive stents was measured over a period of 3 days.
      CONCLUSION: The air-kerma strength of HDR and LDR sources was measured for proof
      of principle and found to agree to within 3% of values obtained with other NIST
      traceable calibration techniques.

PMID- 15737908
TI  - Bouquet brachytherapy: feasibility and optimization of conically spaced implants.
AB  - PURPOSE: To examine the dosimetric feasibility of a conical implantation approach
      to robotic-assisted prostate brachytherapy. METHODS AND MATERIALS: An in-house
      inverse planning software based on the genetic algorithm (GA) was used to
      optimize the needle angulations and the seed positions along needles that form
      one or two bouquets. Volume data from 20 prostate seed implant patients (six 125I
      and 14 103Pd) previously treated using the conventional rectilinear template
      approach were used. The dosimetry outcomes of the optimized treatment plan in the
      conical approach were compared with those from the original treatment plans based
      on the conventional rectilinear template approach. RESULTS: When seed spacing is
      restricted to nominal 1 cm center-to-center spacing, dosimetry results in the
      conical approach suffer from a higher urethra dose and higher dose heterogeneity
      compared with the original rectilinear template plans. When the seed loading
      patterns are optimized as part of inverse planning, the resulting dosimetry plans
      exhibit adequate dose coverage and uniformity through the target volume, as well
      as satisfactory sparing of the urethra and rectum. CONCLUSIONS: Conically spaced
      implantation for prostate brachytherapy with 125I and 103Pd seeds is feasible in
      terms of dosimetry outcomes. Techniques for optimized inverse planning for this
      approach have been developed.

PMID- 15737909
TI  - Proceedings and abstracts of the 9th International Workshop on Virus Evolution
      and Molecular Epidemiology. 13-23 August 2003, Stanford, California, USA.

PMID- 15737910
TI  - Comparative population dynamics of HIV-1 subtypes B and C: subtype-specific
      differences in patterns of epidemic growth.
AB  - The human immunodeficiency virus (HIV) pandemic continues to grow at an alarming
      rate, with a further 5 million new infections in 2003. Some 3.5 million of these
      were in sub-Saharan Africa, where approximately 70% of the world's HIV-positive
      population resides. In contrast, the spread of HIV in high-income countries has
      slowed since its discovery in the 1980s, and in regions such as Western Europe
      prevalence has decreased. Here, we employ coalescent methods to compare the
      epidemic growth rates of two subtypes of HIV-1 with differing epidemiological
      profiles: subtype C, which is dominant in sub-Saharan Africa and associated with
      heterosexual transmission, and subtype B, the main cause of AIDS in Western
      Europe and North America, and which was primarily transmitted through homosexual
      sex and injecting drug use. We show that although both subtypes emerged at
      approximately the same time ( approximately 1960), they have widely differing
      patterns of exponential population growth. At its current growth rate the
      epidemic of subtype C in sub-Saharan Africa is doubling every 2.4 years, which is
      approximately half the rate observed during the early stages of the subtype B
      epidemic in Western Europe and North America. However, the subtype C growth rate
      is still 5-10 times greater than that estimated for the blood-borne hepatitis C
      virus, supporting the hypothesis that sexual transmission has been primarily
      responsible for the HIV epidemic in sub-Saharan Africa.

PMID- 15737912
TI  - Analysis of complex HIV-1 intersubtype recombinants using a Bayesian scanning
      method.
AB  - The increased complexity of HIV-1 genetic heterogeneity raises the issue for
      reliable classification and analysis of these sequences. Until now, bootscanning
      analysis has been the main method used for the analysis of potential HIV-1
      intersubtype recombinants. We show evidence that in some cases of complex
      recombinants, where three or more segments with discordant phylogenetic signal
      may exist in protease (PR) and partial reverse transcriptase (RT) region,
      Bayesian scanning provides a clearer picture than bootscanning plots about the
      boundaries of potential recombination. Thus, a recently developed Bayesian
      scanning tool can facilitate the analysis and classification of HIV-1 mosaic
      sequences.

PMID- 15737911
TI  - The analysis of near full-length genome sequences of human immunodeficiency virus
      type 1 BF intersubtype recombinant viruses from Chile, Venezuela and Spain
      reveals their relationship to diverse lineages of recombinant viruses related to
      CRF12_BF.
AB  - Human immunodeficiency virus type 1 (HIV-1) BF intersubtype recombinant viruses
      are common in Argentina and Uruguay, where CRF12_BF and related recombinants are
      frequently found, and, in a lower proportion, in Brazil. Full-length genome
      sequences have been characterized in several of these recombinant viruses. Here,
      we analyze six newly derived near full-length genome sequences of BF recombinant
      viruses, three from Chile, one from Venezuela and two from Spain. Five of them
      had known epidemiological links to Argentina. Genomes were amplified by PCR from
      plasma RNA or from peripheral blood mononuclear cells' DNA. Mosaic structures and
      phylogenetic relationships were analyzed by bootscanning, neighbour-joining
      phylogenetic trees and by examination of subtype signature nucleotides. One virus
      from Spain had a mosaic structure fully coincident with CRF12_BF. The others had
      unique mosaic structures, except the viruses from two Chilean sisters infected
      vertically from the same mother, who showed identical recombination patterns.
      Each of the unique recombinants had one to six breakpoints coincident with
      CRF12_BF and three also had two or three breakpoints coincident with a previously
      characterized unique recombinant from Argentina (A025) related to CRF12_BF. A
      phylogenetic tree of concatenated subtype F segments supported the relationship
      of five recombinants with CRF12_BF. In trees of partial subtype F and B segments,
      four recombinants clustered with A025. The examination of CRF12_BF signature
      amino acids and nucleotides supported the common ancestry of all the analyzed
      viruses. Based on these results, a model of generation of HIV-1 BF recombinants
      of Argentinean ancestry by successive rounds of recombination along diverse
      lineages deriving from a common BF recombinant ancestor related to CRF12_BF is
      proposed.

PMID- 15737913
TI  - Re-analysis of 34 full-length HIV-1 intersubtype recombinant sequences.
AB  - One of the main characteristics of the HIV-1 is its extensive genetic
      heterogeneity. Intersubtype recombination was first described in 1995 and since
      then a significant proportion of the HIV-1 isolates was found to comprise mosaic
      sequences. Re-analysis of 34 full-length HIV-1 intersubtype recombinants,
      including all "pure" HIV-1 subtypes revealed that 19 of the 34 analyzed mosaics
      consist of a more complex mosaic pattern than initially described. These findings
      indicate that the complexity of the HIV-1 recombinants is much greater than
      previously estimated.

PMID- 15737914
TI  - HIV-1 genetic variants circulation in the North of Angola.
AB  - Few molecular epidemiological data on HIV-1 in Angola are available. In this
      study, we analysed 37 pol sequences from patients originated from Luanda and
      Cabinda in Angola. It was our objective to investigate the circulation of
      different HIV-1 subtypes in this country. We found a high HIV-1 genetic
      diversity. The predominant subtypes were C and F, while subtypes A, D, G and H
      were also detected. Three sequences were untypable and may possibly belong to new
      subtypes or recombinants of unknown subtypes. Moreover, 13 recombinant sequences
      were found, most of them with very complex patterns including untypable
      fragments.

PMID- 15737915
TI  - Evidence for negative selective pressure in HIV-2 evolution in vivo.
AB  - HIV-2 sequence divergence and evolution in vivo has not been well characterized
      so far. To investigate the extent of HIV-2 genetic diversity and better
      understand how HIV-2 evolves in vivo, env C2-C3 nucleotide sequences were
      obtained from the plasma and PBMCs virus populations of four HIV-2 patients with
      different infection periods. Phylogenetic analysis showed that three patients
      were infected with subtype A HIV-2 and the remaining patient was infected with a
      divergent HIV-2 that could not be genotyped. Virus populations from the plasma
      and PBMCs clustered together in all patients suggesting that there is continuous
      and unrestricted virus flow between plasma and PBMCs. HIV-2 genetic diversity was
      not correlated with CD4+ cell counts and plasma viral load. There was a direct
      association between the period of infection and genetic divergence of virus
      populations both in the env C2-C3 and V3 regions such that higher genetic
      diversity was observed in long-term infected patients. In three patients, the
      average frequency of synonymous substitutions (dS) was significantly higher than
      the nonsynonymous substitutions (dN) whereas in the fourth patient the dN/dS
      ratio approached the unity. These data demonstrate that negative selective
      pressure determines the evolution of the HIV-2 env C2-C3 region in vivo. Our
      results suggest that throughout HIV-2 infection low virus adaptation to strong
      selective pressures (e.g. immune pressure) promotes the predominance of a few
      optimally adapted forms.

PMID- 15737917
TI  - Distribution of human papillomavirus genotypes in plucked eyebrow hairs from
      Slovenian males with genital warts.
AB  - In the present study, the presence and distribution of human papillomaviruses
      (HPVs) in the plucked eyebrow hairs obtained from 49 Slovenian male patients with
      genital warts were investigated. Using polymerase chain reaction (PCR) with three
      sets of degenerate primers targeting all known HPV genotypes, HPV DNA was found
      in 31 (63.3%) of 49 eyebrow hair samples. Epidermodysplasia verruciformis (EV)
      associated HPV specific Ma/Ha nested PCR system detected HPVs in 27 (55.1%) and
      CPI/CPIIs primers that amplify the majority of cutaneous/EV HPV genotypes in 20
      (40.8%) of 49 samples tested. The CPI/CPIIg PCR specific for E1 open reading
      frame of genital HPVs showed the presence of HPV DNA in 10 (20.4%) of 49
      specimens. Direct sequencing of the Ha PCR products showed the presence of three
      putative new HPV genotypes, named SIBX1, SIBX2 and SIBX3. Similarly, three
      potential new HPV genotypes, SIBX4, SIBX5 and SIBX6, were detected by sequencing
      CPI/CPIIs PCR products. In total, at least 24 different HPV genotypes were
      detected in 31 HPV DNA positive samples of plucked eyebrow hairs. The results of
      our study showed that the use of a combined degenerate primer PCR approach
      considerably improves the HPV DNA detection over individual primer sets and
      greatly improves the detection of different HPV genotypes in the plucked eyebrow
      hairs.

PMID- 15737916
TI  - Cell membrane proteins and quasispecies compartmentalization of CSF and plasma
      HIV-1 from aids patients with neurological disorders.
AB  - Cell membrane protein (CMP) profile of HIV-1 from cerebrospinal fluid (CSF) and
      plasma of five AIDS patients with neurologic disorders was analyzed and compared
      with viral quasispecies composition in these body compartments. To this aim,
      paired CSF and plasma samples from AIDS subjects with HIV-related neurological
      diseases (three HIV-1 encephalopaty (HIVE) and two primary CNS lymphoma (PCNSL))
      underwent immobilized antibody capture (IAC) assay to determine the profile of
      CMP acquired by HIV-1. The considered CMPs were CD45RO, CD26, CD36, glut-R, N
      CAM, VCAM-1, ELAM-1, CD44 and CD58, representing lymphomonocyte, neuronal and
      adhesion molecules. Cloning and sequencing of env and gag regions was performed
      to predict coreceptor usage and to analyze quasispecies compartmentalization. The
      results indicated that CD44 and CD58 were the most represented molecules on HIV-1
      from CSF, whereas CD36 was the most abundant molecule on plasma HIV-1. V3 env
      aminoacidic sequences and net charge were consistent with M-R5 phenotype in all
      CSF and in most plasma clones. The degree of genetic heterogeneity (both
      complexity and diversity) in p17 gag was significantly lower in CSF-HIV than that
      in plasma-HIV for three patients, higher for one patient, and not significantly
      different for one patient, suggesting compartmentalization for all but the latter
      patient. When considering the pattern of CMP, the most abundant CMP observed in
      HIV from plasma and CSF was different in patients showing compartmentalization,
      while was the same in the patient without significant differences in CSF and
      plasma quasispecies. In conclusion, the present data on CMP pattern, V3 loop
      aminoacidic signature and genetic heterogeneity of HIV-1 quasispecies from CSF
      and plasma of HIVE patients, are consistent with a compartmentalized virus
      replication, at least in some patients, and with a possible different source of
      HIV in the two body sites, even though in a context of a largely prevalent M-R5
      phenotype.

PMID- 15737918
TI  - Phylogenetic analysis and sequence comparisons of structural and non-structural
      SARS coronavirus proteins in Taiwan.
AB  - Taiwan experienced a large number of severe acute respiratory syndrome (SARS)
      viral infections between March and July 2003; by September of that year, 346 SARS
      cases were confirmed by RT-PCR or serological tests. In order to better
      understand evolutionary relationships among SARS coronaviruses (SCoVs) from
      different international regions, we performed phylogenetic comparisons of full
      length genomic and protein sequences from 45 human SCoVs (including 12 from
      Taiwan) and two civet SCoVs. All the Taiwanese SARS-CoV strains which associated
      with nosocomial infection formed a monophyletic clade within the late phase of
      the SARS epidemic. This Taiwanese clade could be further divided into two
      epidemic waves. Taiwan SCoVs in the first wave clustered with three isolates from
      the Amoy Gardens housing complex in Hong Kong indicating their possible origin.
      Of the 45 human SCoVs, one isolate from Guangdong province, China, exhibited an
      extra 29-nucleotide fragment between Orf 10 and Orf 11--similar to the civet SCoV
      genome. Nucleotide and protein sequence comparisons suggested that all SCoVs of
      late epidemic came from human-to-human transmission, while certain SCoVs of early
      epidemic might have originated in animals.

PMID- 15737919
TI  - CCR5 chemokine receptor gene evolution in New World monkeys (Platyrrhini,
      Primates): implication on resistance to lentiviruses.
AB  - The CC chemokine receptor 5 (CCR5) gene of primates encodes a transmembrane
      protein involved in cellular signaling of some cell types of the immune system.
      Numerous studies have shown that this peptide is used by lentiviruses in
      conjunction with the CD4 receptor to mediate binding and entry in target cells of
      human and non-human primates. New World monkeys (NWM), differently from their
      African counterparts, have no description of in natura lentivirus infection. Some
      evidences suggest that a blockage occurs at the viral entry step of infection. To
      investigate this possibility, we have cloned and sequenced CCR5 genes from
      several representatives of Platyrrhini, and compared their sequences with those
      of other Platyrrhini and Catarrhini species available at public databases.
      Platyrrhini CCR5 genes were shown to be more genetically diverse than their
      Catarrhini correlates, and their phylogenetic relationships based on that locus
      were in agreement with previous studies. Comparison of Platyrrhini and Catarrhini
      CCR5 consensus sequences evidenced several amino acid residues that differ
      between both groups, some of which have been experimentally associated with
      lentiviral interaction. A codon-based positive selection analysis showed that
      some of these sites seem to be under strong selection for variation among the
      Platyrrhini but not among Catarrhini species. These results suggest the potential
      involvement of those sites in the apparent refraction of some NWM to
      lentiviruses. The high ccr5 genetic diversity observed in Platyrrhini, however,
      argues for a more extensive infection analysis of diverse NWM species to evaluate
      this resistance and the potential use of those primates as HIV/AIDS animal
      models.

PMID- 15737920
TI  - Prevalence and genetic characterization of caliciviruses among children
      hospitalized for acute gastroenteritis in the United States.
AB  - Human calicivirus was the first recognized viral agent causing gastroenteritis in
      humans. Norovirus (NV) and Sapovirus (SV), two genera within the Caliciviridae
      family, cause epidemic and endemic acute gastroenteritis in children and adults.
      The role of these viruses as a cause of sporadic acute gastroenteritis in young
      children requiring hospitalization is not well established. The aim of this study
      was to assess the prevalence and genetic diversity of caliciviruses among
      children hospitalized with symptoms of acute gastroenteritis. Stool samples were
      collected over 2 years from symptomatic children (N=1840) up to 5 years of age at
      three pediatric hospitals in the US. Overall, 156 (8.5%) samples were CV
      positive, 131 (7.1%) confirmed by sequencing to be NV and 25 (1.4%) confirmed to
      be SV. Sequences of RT-PCR-amplified polymerase gene segments were analyzed using
      distance, maximum likelihood and parsimony algorithms. Phylogenetic analysis of
      97 NV sequences showed that seven strains were in genogroup I, 86 strains were in
      genogroup II and four strains were not in genogroup I, II, or III, likely
      representing three new NV genogroups IV, VI and VII. Genogroup I and genogroup II
      strains were in 12 new genetic clusters, three in genogroup I and nine in
      genogroup II. Within genogroups I and II, most (98%) NV strains were in genetic
      clusters with no known prototype in GenBank. Phylogenetic analysis of 24 SV
      strains showed that half grouped with the London/92 strain in one genogroup and
      the remainder in three other proposed genogroups, one novel. In conclusion, NV
      and SV were frequent causes of hospitalization for acute gastroenteritis in young
      children and infecting strains were highly diverse, including newly recognized
      genogroups and genetic clusters within known genogroups.

PMID- 15737921
TI  - A Bayesian statistical analysis of human T-cell lymphotropic virus evolutionary
      rates.
AB  - HTLV is a genetically-stable retrovirus that is considered to have evolved partly
      in concert with human migrations. Its rate of evolution is low and therefore,
      difficult to estimate reliably. In the first part of this study, we provide an
      improved estimate of HTLV evolutionary rate using anthropological calibration of
      phylogenetic nodes. We investigate two different anthropological calibrations
      using a Bayesian method that implements a relaxed molecular clock model and can
      combine data from multiple genes. The analysis shows that the two calibrations
      are compatible. In the second part, we develop a Bayesian statistical model to
      combine and compare the anthropology-based estimates of evolutionary rate with a
      rate recently calculated using pedigree data from vertically HTLV-infected
      families. We compare the statistical power of the two estimates and show that the
      current pedigree estimate, although resulting in considerably higher evolutionary
      rates, is too statistically weak to warrant a re-examination of the commonly used
      anthropology-based estimates. Statistical uncertainty burdens HTLV rate estimates
      based on both anthropological calibrations and on pedigree data; the former
      method rests on an untested assumption, whilst that latter is affected by small
      sample sizes.

PMID- 15737922
TI  - Finding the hematopoietic stem cell niche in the placenta.
AB  - The origin of definitive hematopoiesis poses a fundamental biological question.
      In this issue of Developmental Cell, two groups have independently found a novel
      hematopoietic stem cell (HSC) niche in the extraembryonic placenta, in addition
      to previously identified alternative locations of hematopoiesis at different
      developmental stages.

PMID- 15737923
TI  - Morphology of mitochondria during apoptosis: worms-to-beetles in worms.
AB  - Although mitochondria are crucial for most pathways of mammalian cell apoptosis,
      evidence for their role in classic invertebrate models of programmed cell death
      has been frustratingly scant. New work showing that inhibition of mitochondrial
      fragmentation during C. elegans development inhibits programmed cell death
      bridges this gap and should advance a more detailed understanding of the role of
      mitochondria in caspase activation.

PMID- 15737924
TI  - Obg/CtgA, a signaling protein that controls replication, translation, and
      morphological development?
AB  - The recent finding that the ObgE GTPase acts as a replication checkpoint protein
      in Escherichia coli has important implications. It reveals the existence of a new
      pathway of replication control by the nucleotide pool and suggests unsuspected
      links between replication, proteins synthesis, and cellular differentiation.

PMID- 15737925
TI  - Emi1 and Erp1: who can stop these eggs?
AB  - Vertebrate eggs prevent parthenogenetic development by producing cytostatic
      factor (CSF), which blocks exit from metaphase of meiosis II until fertilization.
      CSF was never purified but recently suspected to inhibit the anaphase-promoting
      complex (APC), an ubiquitin ligase required for entry into anaphase. In a recent
      paper in Genes & Development, Schmidt et al. describe the Xenopus APC inhibitor
      Erp1, which seems to be the best candidate yet for the downstream effector of CSF
      activity.

PMID- 15737926
TI  - Ras and Rap: are former enemies now friends?
AB  - The small GTPase Rap1 was originally thought to function as an antagonist of Ras.
      A recent paper by provides evidence that Ras and Rap1 function in parallel to
      activate Raf downstream of the Torso receptor tyrosine kinase in Drosophila.

PMID- 15737927
TI  - Gastrulation movements: the logic and the nuts and bolts.
AB  - Gastrulation, the period during the early development of animals when major cell
      and tissue movements remodel an initially unstructured group of cells, requires
      coordinated control of different types of cellular activities in different cell
      populations. A hierarchy of genetic control mechanisms, involving cell signaling
      and transcriptional regulation, sets up the embryonic axes and specify the
      territories of the future germ layers. Cells in these territories modulate their
      cytoskeleton and their adhesive behavior, resulting in shape changes and
      movement. Similarities among different species in patterning and cell biological
      mechanisms are beginning to allow us to recognize general, conserved principles
      and speculate on possible ancestral mechanisms of gastrulation.

PMID- 15737928
TI  - The temporal patterning microRNA let-7 regulates several transcription factors at
      the larval to adult transition in C. elegans.
AB  - The let-7 microRNA is phylogenetically conserved and temporally expressed in many
      animals. C. elegans let-7 controls terminal differentiation in a stem cell-like
      lineage in the hypodermis, while human let-7 has been implicated in lung cancer.
      To elucidate let-7's role in temporal control of nematode development, we used
      sequence analysis and reverse genetics to identify candidate let-7 target genes.
      We show that the nuclear hormone receptor daf-12 is a let-7 target in seam cells,
      while the forkhead transcription factor pha-4 is a target in the intestine.
      Additional likely targets are the zinc finger protein die-1 and the putative
      chromatin remodeling factor lss-4. Together with the previous identification of
      the hunchback ortholog hbl-1 as a let-7 target in the ventral nerve cord, our
      findings show that let-7 acts in at least three tissues to regulate different
      transcription factors, raising the possibility of let-7 as a master temporal
      regulator.

PMID- 15737929
TI  - The Drosophila fragile X protein functions as a negative regulator in the orb
      autoregulatory pathway.
AB  - Translational regulation of maternal mRNAs in distinct temporal and spatial
      patterns underlies many key decisions in developing eggs and embryos. In
      Drosophila, Orb is responsible for mediating the translational activation of
      mRNAs localized within the developing oocyte. Orb is a germline-specific RNA
      binding protein and is one of the founding members of the CPEB family of
      translational regulators. Here we show that Orb associates with the Drosophila
      Fragile X Mental Retardation (dFMR1) protein as part of a ribonucleoprotein
      complex that controls the localized translation of mRNAs in developing egg
      chambers. One of the key orb regulatory targets is orb mRNA, and this
      autoregulatory activity is critical for ensuring that Orb protein is expressed at
      high levels in the oocyte. We show that dFMR1 functions as a negative regulator
      in the orb autoregulatory circuit, downregulating orb mRNA translation.

PMID- 15737930
TI  - Cortical organization by the septin cytoskeleton is essential for structural and
      mechanical integrity of mammalian spermatozoa.
AB  - Septins are polymerizing GTP binding proteins required for cortical organization
      during cytokinesis and other cellular processes. A mammalian septin gene Sept4 is
      expressed mainly in postmitotic neural cells and postmeiotic male germ cells. In
      mouse and human spermatozoa, SEPT4 and other septins are found in the annulus, a
      cortical ring which separates the middle and principal pieces. Sept4-/- male mice
      are sterile due to defective morphology and motility of the sperm flagellum. In
      Sept4 null spermatozoa, the annulus is replaced by a fragile segment lacking
      cortical material, beneath which kinesin-mediated intraflagellar transport
      stalls. The sterility is rescued by injection of sperm into oocytes,
      demonstrating that each Sept4 null spermatozoon carries an intact haploid genome.
      The annulus/septin ring is also disorganized in spermatozoa from a subset of
      human patients with asthenospermia syndrome. Thus, cortical organization based on
      circular assembly of the septin cytoskeleton is essential for the structural and
      mechanical integrity of mammalian spermatozoa.

PMID- 15737931
TI  - The Sept4 septin locus is required for sperm terminal differentiation in mice.
AB  - The murine septin4 gene (Sept4) has been implicated in diverse cellular
      functions, including cytokinesis, apoptosis, and tumor suppression. Here, we
      investigated the function of Sept4 proteins during mouse development by creating
      a targeted deletion of the Sept4 genomic locus. Sept4 mutant mice are viable but
      male sterile due to immotile and structurally defective sperm. During
      spermatogenesis, Sept4 proteins were essential for proper mitochondrial
      architecture and establishment of the annulus, a ring-like structure in the tail
      region of sperm. In addition, Sept4 mutant sperm showed defects in the
      elimination of residual cytoplasm during sperm maturation and had increased
      staining for the caspase inhibitor XIAP. This is consistent with a role of the
      proapoptotic Sept4 protein ARTS in promoting caspase-mediated removal of
      cytoplasm via inhibition of XIAP. Our results indicate that Sept4 proteins play
      distinct but evolutionarily conserved functions in different cellular
      compartments.

PMID- 15737932
TI  - The placenta is a niche for hematopoietic stem cells.
AB  - The hematopoietic system develops during embryogenesis at temporally and
      anatomically restricted sites. The anatomical origin of definitive HSCs is not
      fully resolved, and little is known about how the different fetal hematopoietic
      microenvironments direct HSC development. Here, we show that the mouse placenta
      functions as a hematopoietic organ that harbors a large pool of pluripotent HSCs
      during midgestation. The onset of HSC activity in the placenta parallels that of
      the AGM (aorta-gonad-mesonephros) region starting at E10.5-E11.0. However, the
      placental HSC pool expands until E12.5-E13.5 and contains >15-fold more HSCs than
      the AGM. The expansion of the CD34(+)c-kit(+) HSC pool in the placenta occurs
      prior to and during the initial expansion of HSCs in the fetal liver.
      Importantly, the placental HSC pool is not explained by rare circulating HSCs,
      which appear later. These data support an important, but unappreciated, role for
      the placenta in establishing the mammalian definitive hematopoietic system.

PMID- 15737933
TI  - The murine placenta contains hematopoietic stem cells within the vascular
      labyrinth region.
AB  - In the midgestation murine embryo, several major vascular tissues contain
      hematopoietic stem cell (HSC) activity. These include the aorta-gonad-mesonephros
      region (AGM), yolk sac, and fetal liver. Recently, the placenta was demonstrated
      to harbor hematopoietic progenitors, but it was not examined for HSC activity. We
      demonstrate here that the placenta also harbors adult-repopulating HSCs.
      Placental HSCs begin to be detected at embryonic day (E) 11, and HSC numbers
      increase dramatically between E11 and E12, exceeding the numbers in the
      circulating embryonic blood. Furthermore, all placental HSC activity is
      restricted to the GFP+ fraction of cells in Ly-6A (Sca-1) GFP transgenic embryos.
      Cells coexpressing GFP and endothelial markers CD34 and CD31 are found in the
      embryonic vasculature of the placental labyrinth. Moreover, placental cell
      expression of other HSC markers and transcription factors suggests that HSC
      emergence may occur in the placenta, as has been proposed for other embryonic
      hematopoietic sites.

PMID- 15737934
TI  - Hedgehog signaling is required for adult blood stem cell formation in zebrafish
      embryos.
AB  - Studies with embryonic explants and embryonic stem cells have suggested a role
      for Hedgehog (Hh) signaling in hematopoiesis. However, targeted deletion of Hh
      pathway components in the mouse has so far failed to provide in vivo evidence.
      Here we show that zebrafish embryos mutant in the Hh pathway or treated with the
      Hh signaling inhibitor cyclopamine display defects in adult hematopoietic stem
      cell (HSC) formation but not in primitive hematopoiesis. Hh is required in the
      trunk at three consecutive stages during vascular development: for the medial
      migration of endothelial progenitors of the dorsal aorta (DA), for arterial gene
      expression, and for the formation of intersomitic vessel sprouts. Interference
      with Hh signaling during the first two stages also interferes with HSC formation.
      Furthermore, HSC and DA formation also share Vegf and Notch requirements, which
      further distinguishes them from primitive hematopoiesis and underlines their
      close relationship during vertebrate development.

PMID- 15737935
TI  - Depletion of three BMP antagonists from Spemann's organizer leads to a
      catastrophic loss of dorsal structures.
AB  - Transplanted Spemann's organizer induces dorsal embryonic cell fates such as the
      nervous system and somites, but in normal development, elimination of individual
      organizer signals (such as the bone morphogenetic protein [BMP] antagonists) has
      surprisingly modest effects on these tissues. Thus, the role of BMP antagonists
      may be limited to fine tuning the size of the dorsal domain. However, at least
      five BMP antagonists are specifically expressed in the organizer, and all can
      mimic aspects of organizer function, suggesting overlapping functions. Here, we
      deplete the function of three BMP antagonists, chordin, noggin, and follistatin,
      in Xenopus tropicalis. We demonstrate that this results in catastrophic failure
      of dorsal development and expansion of ventral and posterior fates. We conclude
      that BMP antagonists are required for formation of the neural plate and dorsal
      mesoderm. In addition, our results show that neural specification requires the
      continuous activity of BMP antagonists from blastula through gastrula stages.

PMID- 15737936
TI  - Genetic programs activated by proneural proteins in the developing Drosophila
      PNS.
AB  - Neurogenesis depends on a family of proneural transcriptional activator proteins,
      but the "proneural" function of these factors is poorly understood, in part
      because the ensemble of genes they activate, directly or indirectly, has not been
      identified systematically. We have taken a direct approach to this problem in
      Drosophila. Fluorescence-activated cell sorting was used to recover a purified
      population of the cells that comprise the "proneural clusters" from which sensory
      organ precursors of the peripheral nervous system (PNS) arise. Whole-genome
      microarray analysis and in situ hybridization was then used to identify and
      verify a set of genes that are preferentially expressed in proneural cluster
      cells. Genes in this set encode proteins with a diverse array of implied
      functions, and loss-of-function analysis of two candidate genes shows that they
      are indeed required for normal PNS development. Bioinformatic and reporter gene
      studies further illuminate the cis-regulatory codes that direct expression in
      proneural clusters.

PMID- 15737937
TI  - The noncanonical binding site of the MED-1 GATA factor defines differentially
      regulated target genes in the C. elegans mesendoderm.
AB  - Mesoderm and endoderm in C. elegans arise from sister cells called MS and E,
      respectively. The identities of both of these mesendodermal progenitors are
      controlled by MED-1 and -2, members of the GATA factor family. In the E lineage,
      these factors activate a sequential cascade of GATA factors, beginning with their
      immediate targets, the endoderm-specifying end genes. We report that MED-1 binds
      invariant noncanonical sites in the end genes, revealing that the MEDs are
      atypical members of the GATA factor family that do not recognize GATA sequences.
      By searching the genome for clusters of these MED sites, we have identified 19
      candidate MED targets. Based on their expression patterns, these define three
      distinct classes of MED-regulated genes: MS-specific, E-specific, and E plus MS
      specific. Some MED targets encode transcription factors related to those that
      regulate mesendoderm development in other phyla, supporting the existence of an
      ancient metazoan mesendoderm gene regulatory network.

PMID- 15737938
TI  - Drosophila genome-scale screen for PAN GU kinase substrates identifies Mat89Bb as
      a cell cycle regulator.
AB  - Although traditional organism-based mutational analysis is powerful in
      identifying genes involved in specific biological processes, limitations include
      incomplete coverage and time required for gene identification. Biochemical
      screens using cell transfection or yeast two-hybrid methods are rapid, but they
      are limited by cDNA library quality. The recent establishment of "uni-gene sets"
      has made it feasible to biochemically screen an organism's entire genome.
      Radiolabeled protein pools prepared from the Drosophila Gene Collection were used
      in a Drosophila in vitro expression cloning ("DIVEC") screen for substrates of
      PAN GU kinase, which is crucial for S-M embryonic cell cycles. Ablation of one
      identified substrate, Mat89Bb, by RNAi produces a polyploid phenotype similar to
      that of pan gu mutants. Xenopus embryos injected with Mat89Bb morpholinos arrest
      with polyploid nuclei, and Mat89Bb RNAi in HeLa cells gives rise to
      multinucleated cells. Thus, Mat89Bb plays an evolutionarily conserved role as a
      crucial regulator of both cell cycle and development.

PMID- 15737939
TI  - MAX1 encodes a cytochrome P450 family member that acts downstream of MAX3/4 to
      produce a carotenoid-derived branch-inhibiting hormone.
AB  - The plant shoot body plan is highly variable, depending on the degree of
      branching. Characterization of the max1-max4 mutants of Arabidopsis demonstrates
      that branching is regulated by at least one carotenoid-derived hormone. Here we
      show that all four MAX genes act in a single pathway, with MAX1, MAX3, and MAX4
      acting in hormone synthesis, and MAX2 acting in perception. We propose that MAX1
      acts on a mobile substrate, downstream of MAX3 and MAX4, which have immobile
      substrates. These roles for MAX3, MAX4, and MAX2 are consistent with their known
      molecular identities. We identify MAX1 as a member of the cytochrome P450 family
      with high similarity to mammalian Thromboxane A2 synthase. This, with its
      expression pattern, supports its suggested role in the MAX pathway. Moreover, the
      proposed enzymatic series for MAX hormone synthesis resembles that of two already
      characterized signal biosynthetic pathways: prostaglandins in animals and
      oxilipins in plants.

PMID- 15737940
TI  - Executive function in children, adolescents, and adults with attention deficit
      hyperactivity disorder: introduction to the special issue.

PMID- 15737941
TI  - Construct validity of the auditory continuous performance test for preschoolers.
AB  - Development of diagnostic instruments directed toward neuropsychological
      assessment of preschoolers lags significantly behind those available for school
      age children (DeWolfe, Byrne, & Bawden, 2000). This is particularly true for
      measures of executive function (EF). The Auditory Continuous Performance Test for
      Preschoolers (ACPT-P; Mahone, Pillion, & Hiemenz, 2001) is a computerized, Go-No
      go test developed to measure selected EF skills in preschoolers. First, to
      determine whether performance on the ACPT-P is associated with hearing
      impairment, we compared performance of children with mild hearing loss (MHL) to
      controls on the ACPT-P, and measures of spatial working memory (SWM) and motor
      persistence (MP). There were no differences between performance of the MHL group
      and controls on any of these measures. Second, to examine the construct validity
      of the ACPT-P, we compared performance of 40 preschoolers with ADHD to 40 age-
      and sex-matched controls, using the ACPT-P to measure response preparation,
      sustained attention, and inhibitory control. We also compared these groups on
      measures of SWM and MP. The group with attention deficit hyperactivity disorder
      (ADHD) performed significantly worse than controls on the ACPT-P (omissions, mean
      response time, variability) and MP. The ACPT-P was correlated with the MP, but
      not with the SWM measure. Both the ACPT-P and the MP measures showed low to
      moderate correlations with parent ratings of behavior associated with ADHD. These
      findings support the use of performance-based assessment of executive control
      skills in preschoolers suspected of having ADHD. In this age group, the ACPT-P
      may be particularly useful in assessing sustained attention and response
      preparation and may complement behavior rating scales.

PMID- 15737942
TI  - Neuropsychological analyses of comorbidity between reading disability and
      attention deficit hyperactivity disorder: in search of the common deficit.
AB  - Measures of component reading and language skills, executive functions, and
      processing speed were administered to groups of children with attention deficit
      hyperactivity disorder (ADHD; n = 113), reading disability (RD; n = 109), both RD
      and ADHD (n = 64), and neither RD nor ADHD (n = 151). Groups with RD exhibited
      pronounced deficits on all measures of component reading and language skills, as
      well as significant weaknesses on measures of verbal working memory, processing
      speed, and response inhibition. Groups with ADHD exhibited weaknesses on all
      response-inhibition and processing speed tasks and were impaired on some measures
      of component reading skills and verbal working memory. The group with comorbid RD
      and ADHD exhibited the combination of the deficits in the RD-only and ADHD-only
      groups, providing evidence against the phenocopy and cognitive subtype hypotheses
      as explanations for the co-occurrence of RD and ADHD. Slow and variable
      processing speed was characteristic of all 3 clinical groups, suggesting that
      measures of this domain may be useful for future studies that search for the
      common genes that increase susceptibility to RD and ADHD.

PMID- 15737943
TI  - Impact of gender and age on executive functioning: do girls and boys with and
      without attention deficit hyperactivity disorder differ neuropsychologically in
      preteen and teenage years?
AB  - ADHD is known to have neuropsychological correlates, characterized mainly by
      executive function (EF) deficits. However, most available data are based on
      studies of boys through age 12. Our goal was to assess whether girls with ADHD
      express neuropsychological features similar to those found in boys, and whether
      these impairments are found in both preteen and teen samples. Participants were
      101 girls and 103 boys with DSM-III-R ADHD, and 109 comparison girls and 70 boys
      without ADHD, ages 9 to 17 years. Information on neuropsychological performance
      was obtained in a standardized manner blind to clinical status. Primary
      regression analyses controlled for age, socioeconomic status, learning
      disability, and psychiatric comorbidity. Girls and boys with ADHD were
      significantly more impaired on some measures of EFs than healthy comparisons but
      did not differ significantly from each other. With the exception of 1 test score
      there were no significant Sex x Diagnosis interactions. Moreover, there were no
      more significant interactions among age, gender, and diagnosis than would be
      expected by chance. Neuropsychological measures of EFs were comparably impaired
      in girls compared to boys with ADHD, and these impairments are found at ages 9 to
      12 and ages 13 to 17. These findings suggest that executive dysfunctions are
      correlates of ADHD regardless of gender and age, at least through the late teen
      years.

PMID- 15737944
TI  - Executive functioning in hyperactive children as young adults: attention,
      inhibition, response perseveration, and the impact of comorbidity.
AB  - Tests of several executive functions (EFs) as well as direct observations of
      symptoms of attention deficit hyperactivity disorder (ADHD) during testing were
      collected at the young adult follow-up (M = 20 years) on a large sample of
      hyperactive (H; N = 147) and community control (CC; N = 71) children. The EF
      tasks included tests of attention, inhibition, and response perseveration. The H
      group was subdivided into those with and without ADHD (+ or w/o) at follow-up.
      The H+ADHD group made significantly more inhibition errors than the CC group on a
      Continuous Performance Test (CPT) and showed more ADHD symptoms while performing
      the CPT. The H+ADHD group also displayed more ADHD symptoms during a letter
      cancellation task than did both the hyperactive w/o ADHD and CC groups. Both H
      groups showed slower reaction times during a Card Playing Task. That subset of
      hyperactive probands with Conduct Disorder (CD) displayed significantly more
      perseverative responding on that task than did those without CD, but otherwise it
      did not differ on any other measures. Current level of anxiety contributed
      adversely to both CPT commission errors and ADHD behavior during the CPT.
      Comorbid depression did not contribute to any group differences on these tests.
      Although developmental improvements were found in both the H and the CC groups in
      their CPT inattention and inhibition scores since adolescence, the H groups
      remained distinguishable from the CC groups over this period. We conclude that
      formerly hyperactive children manifest greater EF deficits at follow-up in the
      areas of inattention, disinhibition, and slowed reaction time and greater ADHD
      behavior during testing, but these problems are mostly confined to those with
      current ADHD. Response perseveration, however, was limited to those hyperactive
      children with CD by follow-up, consistent with Quay's theory of these two
      disorders.

PMID- 15737945
TI  - Neural substrates of childhood attention-deficit/hyperactivity disorder:
      electroencephalographic and magnetic resonance imaging evidence.
AB  - Research methods based on electroencephalogram (EEG) and anatomical and
      functional MRI have been used with increasing frequency in the study of childhood
      Attention-Deficit/Hyperactivity Disorder (ADHD). Both methods are safe and
      noninvasive, and their results can complement each other because of the good
      temporal (but relatively poorer spatial) resolution of EEG and the good spatial
      (but relatively poorer temporal) resolution of MRI. These methods are described,
      and associated recent research on childhood ADHD is summarized and critically
      examined. Results of this research support theories of ADHD that focus on a
      frontal-striatal neurological circuitry substrate, which has been implicated in
      neuropsychological executive functioning. A number of issues, however, such as
      the specificity of this finding for ADHD, remain unresolved. We conclude with an
      overview of advances and issues to be considered in future research on the neural
      substrates of childhood ADHD and advocate a developmental-contextual perspective
      on this disorder that acknowledges the reciprocal relations between neural
      structures and functions.

PMID- 15737946
TI  - Expression of beta-defensin 1 and 2 in nasal epithelial cells and alveolar
      macrophages from HIV-infected patients.
AB  - BACKGROUND: The incidence of respiratory infection is high in HIV-infected
      patients. beta-defensins are anti-microbial peptides derived from epithelia on
      the mucosal surfaces of the respiratory, gastrointestinal and urinary tract.
      Nothing is known about the rate of expression of beta-defensin 1 and 2 mRNAs in
      nasal epithelial cells and alveolar macrophages in HIV-infected patients.
      METHODS: Semiquantitative rt-PCR measurement of beta-defensins 1 and 2 and beta
      actin were carried out on nasal epithelial cells of 109 patients (76 HIV
      infected) and alveolar macrophages from 56 patients (18 HIV-infected). RESULTS:
      The levels of beta-defensin 1 and 2 mRNAs in nasal epithelial cells did not
      differ significantly between HIV-infected and non-infected patients. In the nasal
      epithelial cells of HIV-negative patients who suffered from respiratory
      infections beta-defensin levels were decreased. beta-defensin 1 mRNA expression
      was significantly reduced in alveolar macrophages from HIV infected patients.
      beta-defensin 2 mRNA expression in alveolar macrophages was very low. beta
      defensins 1 and 2 mRNA expression did not correlate with CD 4 cell numbers in the
      blood of HIV-infected patients. CONCLUSION: HIV infection and CD 4 cell numbers
      in the blood do not influence beta-defensin 1 and 2 expressions in nasal
      epithelial cells. In alveolar macrophages, beta-defensin 1 expression is
      decreased in HIV-infected patients.

PMID- 15737947
TI  - Atazanavir for treatment of HIV infection in clinical routine: efficacy,
      pharmacokinetics and safety.
AB  - INTRODUCTION: Atazanavir (ATV) is a novel protease inhibitor that has been
      recently introduced into therapy of HIV infection. Currently there is little data
      on ATV therapy from daily practice. METHODS: In this retrospective study, we
      report on ATV efficacy and safety in clinical routine. Drug monitoring was
      performed consisting of unscheduled single measurements and a 4-hour-profile.
      Trough concentration of >80 ng/ml and peak concentration of 2000-6000 ng/ml were
      regarded as sufficient. RESULTS: Between May 2003 and April 2004, ATV treatment
      was started in 42 patients, mean observation time was 32 weeks (6-53). Mean age
      was 45.6 years, 38% had prior AIDS, viral load was undetectable in 73%. Important
      side effects were minor or moderate diarrhea (27%) and fatigue (15%). ATV was
      discontinued in 10% due to side effects or malignant diseases. No significant
      influence on mean values of cholesterol, triglycerides, liver enzymes, CD4-cell
      count, and HI-viral load was seen. Virologic failure occurred in 13% of patients,
      all of them were PI-experienced. Pharmacokinetic data are available for 32
      patients, all patients had sufficient trough levels. 30% with unboosted ATV and
      21% with boosted ATV had peak plasma concentrations below the level defined as
      sufficient. Mean trough levels, plasma profile and AUC did not differ
      significantly between groups with non-boosted versus boosted ATV regimes but
      showed a wide inter-patient variability. CONCLUSIONS: ATV treatment of HIV
      infected patients with or without a RTV booster was safe and effective in
      clinical routine. Drug levels were sufficient in the majority of cases. The
      variability of pharmacokinetic results in our sample supports therapeutic drug
      monitoring in patients treated with ATV.

PMID- 15737948
TI  - Hemofiltrastion does not influence early S-100B serum levels in septic shock
      patients receiving stress doses of hydrocortisone or placebo.
AB  - BACKGROUND: The prognosis in patients with hyperdynamic septic shock correlates
      with the presence and the severity of septic encephalopathy. However, the
      neurological evaluation is considerably influenced by the use of analgesia
      sedation during mechanical ventilation. An early concentration peak of the
      neuroprotein S-100B in serum reflects both cellular damage at an increased
      permeability of the blood-brain-barrier and a delayed renal elimination. Thus,
      the objective of this study was to analyze the effect of continuous veno-venous
      hemofiltration (CVVH) on early S-100B serum levels in septic shock patients, who
      were treated with either stress doses of hydrocortisone or placebo. METHODS:
      Twenty-four consecutive patients, who met the ACCP / SCCM criteria for septic
      shock, were enrolled in this prospective, randomised, double-blind, single-center
      trial. The severity of illness at recruitment was graded using the APACHE II and
      SAPS II scoring systems; the MODS was described by the SOFA score. All patients
      were prospectively randomised to receive either stress doses of hydrocortisone or
      placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg
      and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. RESULTS: Median
      S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/ml (0.19
      .60) at study entry to 0.07 ng/ml (0.04-0.32) 6 days later without significant
      differences compared to the placebo group. Patients undergoing CVVH showed
      significantly higher S-100B serum values compared to patients without CVVH
      (p>0.001). However, initial median S-100B serum levels of the CVVH group even
      increased from 0.92 ng/ml (0.16 - 4.63) to 2.33 ng/ml (0.59-2.44) 30 hours after
      study entry, reaching data ranges already known in patients with out-of-hospital
      cardiac arrest or severe traumatic brain injury. CONCLUSION: Early S-100B serum
      levels in septic shock patients receiving either stress doses of hydrocortisone
      or placebo were not influenced by CVVH. For the first time, we observed a similar
      extent of S-100B serum increase in CVVH patients, who had significantly higher S
      100B serum values compared to those without CVVH, as reported for out-of-hospital
      cardiac arrest or severe traumatic brain injury. Hypercortisolemia induced by the
      infusion of stress doses of hydrocortisone did not significantly reduce early S
      100B serum concentrations with time.

PMID- 15737949
TI  - Incremental cost effectiveness evaluation in clinical research.
AB  - OBJECTIVE: The health economic evaluation of therapeutic and diagnostic
      strategies is of increasing importance in clinical research. Therefore also
      clinical trialists have to involve health economic aspects more frequently.
      However, whereas they are quite familiar with classical effect measures in
      clinical trials, the corresponding parameters in health economic evaluation of
      therapeutic and diagnostic procedures are still not this common. METHODS: The
      concepts of incremental cost effectiveness ratios (ICERs) and incremental net
      health benefit (INHB) will be illustrated and contrasted along the cost
      effectiveness evaluation of cataract surgery with monofocal and multifocal
      intraocular lenses. ICERs relate the costs of a treatment to its clinical benefit
      in terms of a ratio expression (indexed as Euro per clinical benefit unit).
      Therefore ICERs can be directly compared to a pre-specified willingness to pay
      (WTP) benchmark, which represents the maximum costs, health insurers would invest
      to achieve one clinical benefit unit. INHBs estimate a treatment's net clinical
      benefit after accounting for its cost increase versus an established therapeutic
      standard. Resource allocation rules can be formulated by means of both effect
      measures. RESULTS: Both the ICER and the INHB approach enable the definition of
      directional resource allocation rules. The allocation decisions arising from
      these rules are identical, as long as the willingness to pay benchmark is fixed
      in advance. Therefore both strategies crucially call for a priori determination
      of both the underlying clinical benefit endpoint (such as gain in vision lines
      after cataract surgery or gain in quality-adjusted life years) and the
      corresponding willingness to pay benchmark. CONCLUSION: The use of incremental
      cost effectiveness and net health benefit estimates provides a rationale for
      health economic allocation discussions and founding decisions. It implies the
      same requirements on trial protocols as yet established for clinical trials, that
      is the a priori definition of primary hypotheses (formulated as an allocation
      rule involving a pre-specified willingness to pay benchmark) and the primary
      clinical benefit endpoint (as a rationale for effectiveness evaluation).

PMID- 15737950
TI  - Detection of occult high graded microsatellite instabilities in MMR gene mutation
      negative HNPCC tumors by addition of complementary marker analysis.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal
      dominant tumor syndrome predisposing to predominantly colorectal and endometrial
      cancer. In 90% of the cases, molecular analyses reveal microsatellite
      instabilities due to germline mutations in DNA mismatch repair (MMR) genes,
      mainly MLH1, MSH2, among these tumors. PATIENTS AND METHODS: Tumors from 40 HNPCC
      index patients (31 Amsterdam positive, 9 Bethesda positive; 21 females, 19 males;
      mean age 48.0 +/- 13.2 years) were examined. In contrast to the classical
      constellation, their tumors revealed only a microsatellite stable (MSS, n=31)--or
      low instable (MSI-L, n=9)--tumor phenotype following the international reference
      panel of 5 microsatellites. No MLH1 and MSH2 mutations were detectable.
      Complementary microsatellites (BAT40, D10S197, D13S153, D18S58, MYCL1) were
      investigated by PCR and fragment analysis to find other instabilities which might
      hint to the MIN-pathway of the tumors. RESULTS: Due to ten microsatellites in
      total tumors were now reclassified in 4 MSI-H (10%), 24 MSI-L (60%) and 12 in MSS
      (30%) phenotypes. The mean age of onset for CRCs was the lowest in the MSI-H
      group with 45.7 +/- 9.6 years (vs. 48.7 +/- 14.3 and 49.0 +/- 12.9 years in MSI-L
      and MSS group). MSI-H-and MSI-L tumors were often localized in the proximal colon
      (50 and 52%), whereas MSS tumors were preferentially localized in the distal
      colon (77%). - CONCLUSION: Complementary microsatellites help to subdive "non
      classical" HNPCC in subgroups with different clinical appearance. It allows to
      detect occult MSI-H tumors with up to 10% and to confirm MSS tumors who seem to
      have a similar biological behaviour like sporadic CRC. Maybe that this genetic
      reclassification influence the decision of whether to offer patients chemotherapy
      or not, since it is known that patients with instable tumors do not benefit from
      chemotherapy as well as patients with microsatellite stable tumors.

PMID- 15737951
TI  - A randomized, placebo-controlled study of the use of filgrastim in non
      neutropenic patients with nosocomial pneumonia.
AB  - Pneumonia remains the number one cause of death from infectious diseases in
      Western Europe and the United States despite the introduction of potent broad
      spectrum antibiotics. Granulocyte colony-stimulating factor is considered to
      improve host defense during infection and may be an effective adjunctive in the
      treatment of severe infections. We examined the efficacy of granulocyte colony
      stimulating factor (r-metHUG-CSF, filgrastim) with regard to clinical response in
      non-neutropenic ICU patients with nosocomial pneumonia in a prospective,
      randomized, placebo-controlled trial. 28 patients with newly diagnosed nosocomial
      pneumonia were randomly assigned to receive 300-480 microg filgrastim or placebo
      subcutaneously for up to seven days. Study endpoints were death within 15 days,
      duration of antibiotic therapy and occurrence of serious adverse events (SAE). No
      significant differences were observed in respect of 15-day (filgrastim1/12 vs.
      placebo 2/16) or 30-day mortality (1/12 vs.4/16, p=0.355), and length of
      antibiotic treatment (13.5 vs.11.5 days, p=0.985). Sepsis developed in 1/12
      patients in the filgrastim and 6/16 patients in the placebo group (p=0.184). None
      of the patients developed ARDS or any other SAE related to the study medication.
      Filgrastim is safe in non-neutropenic ICU patients with nosocomial pneumonia. A
      benefit of filgrastim with regard to clinical endpoints could not be observed,
      while there was a trend toward reduced sepsis rate.

PMID- 15737952
TI  - The effect of breastfeeding on weight gain in infants: results of a birth cohort
      study.
AB  - The objective of this study was to examine whether duration of exclusive
      breastfeeding is associated with elevated weight gain in infants during the first
      two years of life. In this prospective cohort study 2624 healthy term neonates
      were followed from birth to age 2 years in 4 German study centres. Data on
      breastfeeding and potential confounders were gathered by questionnaires. Data on
      anthropometric measures at birth and age 2 years were obtained from routine
      standardised medical check up documentation. Odds ratios for the association
      between breastfeeding and weight gain until age 2 years (> or = 90th sex-specific
      percentile of the cohort) were calculated by logistic regression, adjusting for
      age at introduction and composition of solid food, maternal BMI, maternal smoking
      during pregnancy, socioeconomic status, study centre, birth order and, in
      unstratified analysis, sex. Children exclusively breastfed for less than 6 months
      had a greater risk of elevated weight gain at the age of 2 years than children
      breastfed for 6 months and more (OR (95% CI): 1.65 (1.17, 2.30)). Duration of
      exclusive breastfeeding was inversely associated with the risk of elevated weight
      gain in a strongly duration-dependent way. Those infants who were exclusively
      breastfed 1 month at the most had twice as often elevated weight gain (OR (95%
      CI): 1.99 (1.34, 2.97)) compared to infants breastfed at least 6 months. Our data
      show that exclusive breastfeeding protects against elevated weight gain during
      infancy which may be the first step on the pathway of obesity development.

PMID- 15737953
TI  - Management of chronic hepatitis C in HIV-co-infected patients--results from the
      First International Workshop on HIV and Hepatitis Co-infection, 2nd-4th December
      2004, Amsterdam, Netherlands.
AB  - About 30% of HIV-positive individuals are concomitantly infected with HCV within
      the United States and Europe. Approximately 50 to 90 % of persons who acquired
      HIV from injecting drugs are co-infected with HCV. In these dually infected
      individuals the presence of each viral infection may impact the natural course of
      the other one, and worsening of associated liver disease and complications within
      this population are frequent. The management of chronic hepatitis C (cHC) in HCV
      HIV-co-infection has become a major challenge, as possible interactions with
      antiretroviral therapy (ART), increased risk of special side effects, as well as
      compromises in adherence of patients, who already take several drugs, have to be
      taken into account. Treatment strategies to fight HCV-infection have been
      essentially ameliorated during the past three years in using pegylated interferon
      alpha (PegIFN alpha) combined with ribavirin (Rbv). There is hope that the
      beneficial therapeutic outcome in HCV-mono-infected individuals may be at least
      partly translated into successful treatment of dually infected patients too.
      However, the stepwise amelioration of therapeutic options and strategies does
      actually not yet result in equal anti-HCV response rates for co-infected compared
      to HCV-mono-infected persons. The 1st International Workshop on HIV and Hepatitis
      Co-infection 2004, was initiated to face the severe clinical problems which arise
      from viral hepatitis and HIV dual infection. The organising committee was headed
      by J. K. Rockstroh, University of Bonn, Germany, as chair and M. Sulkowski, John
      Hopkins University, USA, as co-chair of the meeting, in which more than 300
      researchers and physicians from various European and US locations participated.
      This report summarizes some results on epidemiology, pathogenesis, viral
      interactions, and treatment of chronic hepatitis C in HIV-infected individuals.

PMID- 15737954
TI  - Polyspecific organic cation transport: insights into the substrate binding site.
AB  - Positively charged endogenous and exogenous organic compounds of diverse chemical
      structures are transported by polyspecific organic cation transporters (OCT). In
      two contributions to the May 2005 issue of Molecular Pharmacology, amino acid
      residues within the fourth and tenth transmembrane helices of rat OCT1 are
      described that contribute to cation and corticosterone binding. In a three
      dimensional model based on the structure of the lactose permease, these residues
      are located in a large grove, the binding site for biogenic amines and cationic
      drugs.

PMID- 15737956
TI  - Spirometry, measurement, and race in the nineteenth century.
AB  - Race correction is a common practice in contemporary pulmonary medicine that
      involves mathematical adjustment of lung capacity measurements in populations
      designated as "black" using standards derived largely from populations designated
      as "white." This article traces the history of the racialization and gendering of
      spirometry through an examination of the ideas and practices related to lung
      capacity measurements that circulated between Britain and the United States in
      the nineteenth century. Lung capacity was first conceptualized as a discrete
      entity of potential use in the diagnosis of pulmonary disease and monitoring of
      the vitality of the armed forces and other public servants in spirometric studies
      conducted in mid-nineteenth-century Britain. The spirometer was then imported to
      the United States and used to measure the capacity of the lungs in a large study
      of black and white soldiers in the Union Army sponsored by the U.S. Sanitary
      Commission at the end of the Civil War. Despite contrary findings and
      contestation by leading black intellectuals, the notion of mean differences
      between racial groups in the capacity of the lungs became deeply entrenched in
      the popular and scientific imagination in the nineteenth century, leaving
      unexamined both the racial categories deployed to organize data and the
      conditions of life that shape lung function.

PMID- 15737955
TI  - Compounds that bind APP and inhibit Abeta processing in vitro suggest a novel
      approach to Alzheimer disease therapeutics.
AB  - Extracellular deposits of aggregated amyloid-beta (Abeta) peptides are a hallmark
      of Alzheimer disease; thus, inhibition of Abeta production and/or aggregation is
      an appealing strategy to thwart the onset and progression of this disease. The
      release of Abeta requires processing of the amyloid precursor protein (APP) by
      both beta- and gamma-secretase. Using an assay that incorporates full-length
      recombinant APP as a substrate for beta-secretase (BACE), we have identified a
      series of compounds that inhibit APP processing, but do not affect the cleavage
      of peptide substrates by BACE1. These molecules also inhibit the processing of
      APP and Abeta by BACE2 and selectively inhibit the production of Abeta(42)
      species by gamma-secretase in assays using CTF99. The compounds bind directly to
      APP, likely within the Abeta domain, and therefore, unlike previously described
      inhibitors of the secretase enzymes, their mechanism of action is mediated
      through APP. These studies demonstrate that APP binding agents can affect its
      processing through multiple pathways, providing proof of concept for novel
      strategies aimed at selectively modulating Abeta production.

PMID- 15737957
TI  - Policing the social boundaries of the American Medical Association, 1847-70.
AB  - In May 1870 the American Medical Association (AMA) voted to deny the admission of
      black delegates and their white colleagues to the national meeting in Washington,
      D.C. Historians of race and medicine have customarily viewed this decision as
      marking a crucial milestone in the formation of the nexus between racism and the
      development of the American medical profession in the era after the Civil War
      (1861-64). This study recasts this narrative by locating the 1870 decision in
      relation to the antebellum practices of the association and their social
      consequences for American medicine. It argues that the viability of the AMA as
      the national voice of the profession was critically dependent on rejecting racial
      equality. Indeed, at a moment when the question of the abolition of slavery
      polarized the nation, the AMA was founded in 1847 to create a voluntary
      professional organization, national in scope, dedicated to raising the standards
      of medical training and practice. To this end, the AMA elected presidents and
      selected host cities for annual meetings in the North, South, and West. Seven out
      of the fourteen meetings and six out of fourteen presidents were from slave
      and/or border states. These institutional practices together with the
      representation of blacks as different and enjoying an appropriate status as
      slaves grounded the national identity of the profession in black subordination.
      Similarly, the gendered discourses about healing and practices of female
      exclusion privileged medical authority as male by drawing on and reinforcing
      patriarchy. In the wake of the war, leaders hoped to restore the national
      character of the organization by resuming antebellum practices. In response to
      the new possibilities for blacks in medicine--as represented by the biracial
      National Medical Society--the AMA took steps to vigorously police the racial
      boundaries of the national profession. As this study will show, the 1870 decision
      reflected the logic of the racial politics at the heart of the association's
      antebellum past and would loom large in its future.

PMID- 15737958
TI  - A world apart: geography, Australian quarantine, and the mother country.
AB  - In many respects the Australian colonies were what one person called "the proud
      offspring of a grand old mother." Yet when it came to the prevention of imported
      infectious disease, Britain's Australian colonies were not a chip off the old
      block. British opposition to the lengthy and costly imposition of quarantine had
      intensified throughout the nineteenth century, eventuating in the abolition of
      human quarantine in 1896. The Australian colonies, on the other hand, which had
      based their first quarantine regulations on British law and remained constantly
      aware of changing medical trends in the mother country, gradually expanded the
      breadth and capabilities of their maritime quarantine as the century progressed.
      Although other European powers and British colonies progressively adopted systems
      of medical inspection more in line with British port prophylaxis and away from
      quarantine, the Australian colonies invested increasing amounts of time and money
      into more elaborate quarantine stations and regulations. In this article I
      examine some of the basic features of coastal disease prevention in the
      Australian colonies and how they differed from British controls. Australia's
      distance from Britain was emphasized in the quarantine debates geographically as
      well as in policy. I argue that the often controversial differences in quarantine
      policy were for the most part a product of Australia's geographical location. The
      natural prophylactic of Australia's remoteness was not a reason to minimize
      quarantine in the colonies but rather served to increase it; whereas, it was
      argued that "the geographical position of England deprived it of the
      advantages...derived from a comprehensive quarantine system." I discuss this
      seeming anomaly in light of other arguments that have claimed that the close
      proximity of a state to the acknowledged origin of a disease was likely to
      increase its eagerness to quarantine.

PMID- 15737959
TI  - A Response to William Kingston, "Streptomycin, Schatz versus Waksman, and the
      balance of credit for discovery".

PMID- 15737961
TI  - Dynamics of urinary levels of hCG during early pregnancy and accuracy of the home
      pregnancy test.
AB  - The paper 'Dynamics of urinary levels of hCG during early pregnancy and accuracy
      of the home pregnancy test' has been retracted at the request of the authors.
      Since initiating the work 3 years ago improvements have been made to home
      pregnancy tests, and the device used in the study is no longer commercially
      available. The authors are conducting a similar study with a new pregnancy test
      device which suggests that some of the conclusions drawn in the retracted paper
      could now be misleading to health professionals and consumers.

PMID- 15737962
TI  - Drug-eluting stents compared with thin-strut bare stents for the reduction of
      restenosis: a prospective, randomized trial.
AB  - AIM: Drug-eluting stents have considerably reduced restenosis. Their relative
      merits have been assessed on the basis of comparisons made with control bare
      stents with thick struts. However, increased strut thickness negatively affects
      restenosis. No direct comparisons between drug-eluting stents and bare stents
      with thin struts have been performed. The aim of this study was to evaluate the
      relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of
      bare stents with thin struts (BeStent 2). METHODS AND RESULTS: A total of 500
      patients with coronary artery disease were randomly assigned to receive a Cypher
      stent or BeStent. The primary endpoint was angiographic restenosis defined as a
      stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary
      endpoint was the need for target vessel revascularization (TVR) during the year
      following the procedure. Follow-up angiography was performed in 81.8% of the
      patients. Patients treated with Cypher stents had a lower angiographic restenosis
      rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56),
      P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22
      0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis
      rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For
      larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the
      Cypher stent and 13.1% with the BeStent (P=0.52). CONCLUSION: The drug-eluting
      stent, Cypher, is associated with a significantly lower risk of restenosis
      compared with the bare thin-strut BeStent. The advantage of the Cypher stent is
      vastly reduced in large vessels.

PMID- 15737964
TI  - Factors affecting a mother's recall of her baby's birth weight.
AB  - BACKGROUND: The Millennium Cohort Study of UK babies born this century obtained
      maternal report of birth weight and data on the family's characteristics,
      including parental ethnicity, education, and social circumstances. Parental
      permission to link babies to their birth registration data provided the
      opportunity to investigate factors affecting accuracy of maternal recall of birth
      weight and to determine possible causes of error. METHODS: Logistic regression
      was used to investigate the relationship between maternal factors and recall of
      birth weight. Numerical and graphical methods were used to identify potential
      causes for birth weight discrepancies. RESULTS: Data were obtained from the birth
      registry and Millennium Cohort Study for 11 890 of the 14 294 cohort children
      born in England and Wales. Weight was reported in imperial units by 84% of
      mothers and this was more common in younger mothers. Accuracy within 100 g was
      92% overall, varying from 94% among British/Irish white mothers to 69-89% for
      other ethnic groups and was lower among the long-term unemployed and those living
      in disadvantaged or ethnic wards. Explanations (mostly rounding and transcription
      errors) were identified for 27% of the discrepancies of 100 g or more. Conclusion
      Mothers' reports of their infants' birth weight showed high level of agreement
      with registration data, the mean discrepancy being consistently close to zero.
      However, the variance of the discrepancy differed according to ethnic group, ward
      type, and socioeconomic status. These sources of differential variability should
      be taken into account in analyses using birth weight, and possibly other reported
      data, from socially mixed populations.

PMID- 15737965
TI  - Causes of death in the Sami population of Sweden, 1961-2000.
AB  - BACKGROUND: Indigenous people often have a pattern of mortality that is
      disadvantageous in comparison with the general population. The knowledge on
      causes of death among the Sami, the natives of northern Scandinavia, is limited.
      The aim of the present study was to compare gender and cause specific mortality
      patterns for reindeer herding Sami, non-herding Sami, and non-Sami between 1961
      and 2000. METHODS: A Sami cohort was constructed departing from a group of index
      Sami identified as either reindeer herding Sami or Sami eligible to vote for the
      Sami parliament. Relatives of index-Sami were identified in the National Kinship
      Register and added to the cohort. The cohort contained a total of 41 721 people
      (7482 reindeer herding Sami and 34 239 non-herding Sami). A demographically
      matched non-Sami reference population four times as large, was compiled in the
      same way. Relative mortality risks were analysed by calculating standardized
      mortality ratios (SMRs). RESULTS: The differences in overall mortality and life
      expectancy of the Sami, both reindeer herding and non-herding, compared with the
      reference population were relatively small. However, Sami men showed
      significantly lower SMR for cancers but higher for external causes of injury. For
      Sami women, significantly higher SMR was found for diseases of the circulatory
      system and diseases of the respiratory system. An increased risk of dying from
      subarachnoid haemorrhage was observed among both Sami men and women. CONCLUSIONS:
      The similarities in mortality patterns are probably a result of centuries of
      close interaction between the Sami and the non-Sami, while the observed
      differences might be due to lifestyle, psychosocial and/or genetic factors.

PMID- 15737966
TI  - Neighbourhood deprivation and alcohol consumption: does the availability of
      alcohol play a role?
AB  - BACKGROUND: Previous studies suggest that the physical availability of alcohol
      may mediate the association between neighbourhood-level material deprivation and
      alcohol consumption. This study tests the relationships between neighbourhood
      level deprivation, alcohol availability, and individual-level alcohol consumption
      using a multilevel analysis. METHODS: Data are from cross-sectional surveys
      conducted between 1979 and 1990 as part of the Stanford Heart Disease Prevention
      Program (SHDPP). Women and men (n = 8197) living in four northern/central
      California cities and 82 neighbourhoods were linked to neighbourhood deprivation
      variables derived from the US census (e.g. unemployment, crowded housing) and to
      measures of alcohol availability (density of outlets in the respondent's
      neighbourhood, nearest distance to an outlet from the respondent's home, and
      number of outlets within a half mile radius of the respondent's home). Separate
      analyses were conducted for on- and off-sale outlets. RESULTS: The most deprived
      neighbourhoods had substantially higher levels of alcohol outlet density than the
      least deprived neighbourhoods (45.5% vs 14.8%, respectively). However, multilevel
      analyses showed that the least deprived neighbourhoods were associated with the
      heaviest alcohol consumption, even after adjusting for individual-level
      sociodemographic characteristics (OR 1.30, CI 1.08-1.56). Alcohol availability
      was not associated with heavy drinking and thus did not mediate the relationship
      between neighbourhood deprivation and heavy alcohol consumption. CONCLUSIONS:
      Although alcohol availability is concentrated in the most deprived
      neighbourhoods, women and men in least deprived neighbourhoods are most likely to
      be heavy drinkers. This mismatch between supply and demand may cause people in
      the most deprived neighbourhoods to disproportionately suffer the negative health
      consequences of living near alcohol outlets.

PMID- 15737967
TI  - Temporal variation in deaths related to alcohol intoxication and drinking.
AB  - BACKGROUND: Temporal variation in deaths related to alcohol intoxication is
      examined using two approaches. First, we examine the risk of these deaths during
      festivals, on the day preceding them, and on the three days that immediately
      follow them. Second, we assess the weekday variation in deaths, and compare this
      with survey-based data on weekday variations in drinking. Previously no data
      existed on the temporal association between intoxication-related deaths and
      drinking occasions according to the severity of intoxication. METHODS: We used
      population registration data on 15-69-year-old men and women, linked with the
      national cause of death register for the years 1987-2001, and the Finnish
      Drinking Habits Survey carried out in 2000. Intoxication-related deaths were
      defined on the basis of underlying and contributory causes of death. RESULTS: The
      largest increased risk of intoxication-related deaths was observed for Midsummer
      Day [Observed deaths/Expected deaths (O/E) = 2.88 (95% confidence interval 2.48
      3.31) for men and O/E = 2.21 (1.43-3.27) for women respectively], Midsummer Eve
      [O/E = 2.70 (2.32-3.12) and 3.18 (2.23-4.41)], May Day [O/E = 1.80 (1.50-2.16)
      and 2.65 (1.79-3.79)], Christmas Eve [O/E = 1.58 (1.29-1.91) and 2.21 (1.43
      3.27)], and New Year's Day [O/E = 1.48 (1.20-1.80) and 1.77 (1.08-2.74)]. Among
      men, the increased risk at Midsummer lasted for three consecutive days. The
      weekday distribution of different levels of intoxication and of intoxication
      related deaths was similar, with a clear increase observed on Friday, Sunday,
      and, particularly, Saturday. CONCLUSIONS: Intoxication-related deaths peak during
      weekends and around festival days when alcohol is widely consumed in excess.
      Public awareness of the risks attached to binge drinking should be increased.

PMID- 15737968
TI  - Temporary employment and health: a review.
AB  - OBJECTIVES: We aimed to review evidence on the relationship between temporary
      employment and health, and to see whether the association is dependent on outcome
      measure, instability of employment, and contextual factors. METHOD: We
      systematically searched for studies of temporary employment and various health
      outcomes and critically appraised 27 studies. RESULTS: The review suggests higher
      psychological morbidity among temporary workers compared with permanent
      employees. According to some studies, temporary workers also have a higher risk
      of occupational injuries but their sickness absence is lower. Morbidity may be
      higher in temporary jobs with high employment instability and in countries with a
      lower number of temporary workers and unemployed workers. CONCLUSIONS: The
      evidence indicates an association between temporary employment and psychological
      morbidity. The health risk may depend on instability of temporary employment and
      the context. Confounding by occupation may have biased some of the studies.
      Additional research to clarify the role of employment instability, hazard
      accumulation, and selection is recommended.

PMID- 15737969
TI  - HIV-1 subtype E progression among northern Thai couples: traditional and non
      traditional predictors of survival.
AB  - BACKGROUND: In the continuing effort to introduce antiretroviral therapy in
      resource-limited settings, there is a need to understand differences between
      natural history of HIV in different populations and to identify feasible clinical
      measures predictive of survival. METHODS: We examined predictors of survival
      among 836 heterosexuals who were infected with HIV subtype CRF01_AE in Thailand.
      RESULTS: From 1993 to 1999, 269 (49.4%) men and 65 (25.7%) women died. The median
      time from the estimated seroconversion to death was 7.8 years (95% confidence
      interval 7.0-9.1). Men and women with enrolment CD4 counts <200 cells/microl had
      about 2 and 11 times greater risk of death than those with CD4 counts of 200-500
      and >500, respectively. Measurements available in resource-limited settings,
      including total lymphocyte count (TLC), anaemia, and low body mass index (BMI),
      also predicted survival. Men with two or more of these predictors had a median
      survival of 0.8 (0.5-1.8) years, compared with 2.7 (1.9-3.3) years for one
      predictor and 4.9 (4.1-5.2) years for no predictors. CONCLUSIONS: The time from
      HIV infection to death appears shorter among this Thai population than among
      antiretroviral naive Western populations. CD4 count and viral load (VL) were
      strong, independent predictors of survival. When CD4 count and VL are
      unavailable, individuals at high risk for shortened HIV survival may be
      identified by a combination of low TLC, anaemia, and low BMI. This combination of
      accessible clinical measures of the disease stage may be useful for medical
      management in resource-limited settings.

PMID- 15737970
TI  - Is it possible to reduce AIDS deaths without reinforcing socioeconomic
      inequalities in health?
AB  - BACKGROUND: The wide use of highly active antiretroviral therapy has led to an
      impressive improvement in AIDS survival after the mid-1990s in cities and
      countries with a high access to these medications. Notwithstanding its beneficial
      overall effect, antiretroviral therapy was also reported as a factor for the
      increase in socioeconomic inequalities in health, because AIDS patients have
      unequal access and adherence to these medications. METHODS: We assessed trends
      AIDS mortality in districts of Sao Paulo, Brazil, from 1995 to 2002, in order to
      test their association with area-level socioeconomic indices in a city with a
      large-scale and cost-free distribution of highly active antiretroviral therapy.
      We gathered information on yearly death rates due to AIDS, adjusted for gender,
      age group, income, instruction, living standards, and the human development
      index. Trend estimation used the autoregression procedure of exact maximum
      likelihood estimation for time-series analysis. Regression analysis was used to
      study the association between the annual percentage decrease in AIDS deaths and
      socioeconomic indices. RESULTS: AIDS mortality decreased in Sao Paulo from 32.1
      deaths (per 100 000 inhabitants) in 1995 to 11.2 deaths (per 100 000 inhabitants)
      in 2002. District-level figures of social development did not show an association
      with the annual percentage decrease in AIDS mortality, with all correlation
      coefficients corresponding to P-values >0.27. CONCLUSIONS: This observation
      indicates that the perspective of public policies addressed to the entire
      population contribute to reducing inequalities in health, while attaining an
      overall reduction in AIDS deaths, may have been feasible in the Brazilian
      context.

PMID- 15737971
TI  - Low uptake of prenatal screening for Down syndrome in minority ethnic groups and
      socially deprived groups: a reflection of women's attitudes or a failure to
      facilitate informed choices?
AB  - BACKGROUND: It is not known if lower uptake of prenatal screening for Down
      syndrome in women from minority ethnic groups and socioeconomically disadvantaged
      women reflects more negative attitudes towards undergoing the test or women not
      acting in line with their attitudes i.e. not making an informed choice. METHODS:
      Uptake of prenatal screening, attitudes towards undergoing the test, uptake
      attitude consistency, and informed choice were assessed in a prospective study of
      1499 pregnant women attending two UK hospitals. RESULTS: Uptake was higher in
      white and socioeconomically advantaged women than in other women. There were no
      differences in attitudes towards undergoing the test; all women expressed
      relatively positive attitudes. Uptake-attitude consistency was higher in white
      and socioeconomically advantaged women than others, particularly in those with
      positive attitudes towards undergoing the test (76% white women with positive
      attitudes had the test compared with 45% South Asian women [difference 31%, 95%
      confidence interval (95% CI) 18-43] and 78% socioeconomically advantaged women
      compared with 63% more disadvantaged women (difference 15%, 95% CI 7-24)).
      Controlling for demographic variables, South Asian and socioeconomically
      disadvantaged women with positive attitudes were less likely to make an informed
      choice than other women [odds ratio (OR) 0.22, 95% CI 0.10-0.45 and OR 0.62, 95%
      CI 0.41-0.93, respectively]. CONCLUSION: Lower uptake of screening for Down
      syndrome in women from minority ethnic groups and socioeconomically disadvantaged
      women does not reflect more negative attitudes towards screening but rather lower
      rates of informed choice, as assessed in this study. Healthcare systems appear to
      facilitate informed choices in the context of prenatal screening for Down
      syndrome screening less well for women from minority ethnic groups and those who
      are socioeconomically disadvantaged than for other women.

PMID- 15737972
TI  - Adult chronic disease and childhood obesity: a life course approach in developing
      countries?

PMID- 15737974
TI  - Case-control study of indoor cooking smoke exposure and cataract in Nepal and
      India.
AB  - BACKGROUND: The prevalence of cataract is higher in developing countries, and in
      both developed and developing countries more females than males are blind from
      cataracts. Three epidemiological studies have associated indoor cooking with
      solid fuels (e.g. wood or dung) and cataract or blindness. However, associations
      in these studies may have been caused by unmeasured confounding. METHODS: A
      hospital-based case-control study was conducted on the Nepal-India border. Cases
      (n = 206) were women patients, aged 35-75 years with confirmed cataracts.
      Controls (n = 203), frequency matched by age, were patients attending the
      refractive error clinic at the same hospital. A standardized questionnaire was
      administered to all participants. Logistic regression analysis involved
      adjustment for age, literacy, residential area, ventilation, type of lighting,
      incense use, and working outside. RESULTS: Compared with using a clean-burning
      fuel stove (biogas, LPG, or kerosene), the adjusted odds ratio (OR) for using a
      flued solid-fuel stove was 1.23 [95% confidence interval (CI) 0.44-3.42], whereas
      use of an unflued solid-fuel stove had an OR of 1.90 (95% CI 1.00-3.61). Lack of
      kitchen ventilation was an independent risk factor for cataract (OR 1.96; 95% CI
      1.25-3.07). CONCLUSION: This study provides confirmatory evidence that use of
      solid fuel in unflued indoor stoves is associated with increased risk of cataract
      in women who do the cooking. The association is not likely to be due to bias,
      including confounding, and strengthens the findings of three previous studies.
      Replacing unflued stoves with flued stoves would greatly reduce this risk,
      although cooking with cleaner-burning fuels would be the best option.

PMID- 15737975
TI  - Social capital. Response.

PMID- 15737976
TI  - Assessing the potential health impact of the 1991 Gulf War on Saudi Arabian
      National Guard soldiers.
AB  - BACKGROUND: There has been considerable publicity that the 1991 Gulf War may have
      caused a wide array of health problems in military personnel. Although post-war
      health outcomes have been studied in US, British, Canadian, Danish, and other
      deployed troops, this issue has not been previously evaluated in coalition forces
      native to the Gulf region. METHODS: A collaborative team of US and Saudi health
      researchers was assembled, data sources evaluated, and hospitalizations among
      Saudi Arabian National Guard (SANG) soldiers between 1991 and 1999 analysed.
      Multivariate modelling was used to evaluate differences between 8342 soldiers
      exposed to combat at Al Khafji and a comparison group of 7270 soldiers in the
      Riyadh area. RESULTS: Among 15 612 SANG soldiers, we identified 148 with at least
      one hospitalization over the 9 years following the war. The adjusted rate of
      hospitalization was higher in the combat-exposed group (risk ratio (RR) = 1.80,
      95% confidence interval (CI) 1.25-2.59). No unusual patterns of diagnoses were
      found and, because the overall number of hospitalizations was low, the absolute
      difference in risk was found to be very small. CONCLUSIONS: This is the first
      reported epidemiological investigation of post-war hospitalizations among
      coalition forces native to the Gulf region that participated in the 1991 Gulf
      War. A very small increase in hospitalizations was identified in SANG soldiers
      exposed to combat at Al Khafji. However, because of data limitations, the
      clinical relevance of this finding should be interpreted with caution. Future
      collaborative studies to better understand the health effects of deployment
      should be encouraged.

PMID- 15737977
TI  - Global trends in breast cancer incidence and mortality 1973-1997.
AB  - BACKGROUND: Worldwide, breast cancer is the most common cancer and is the leading
      cause of cancer death among women. METHODS: To describe global trends, we
      compared age-adjusted incidence and mortality rates over three decades (from 1973
      77 to 1993-97) and across several continents. RESULTS: Both breast cancer
      incidence and mortality rates varied 4-fold by geographic location between
      countries with the highest and lowest rates. Recent (1993-1997) incidence rates
      ranged from 27/100,000 in Asian countries to 97/100,000 among US white women.
      Overall, North American and northern European countries had the highest incidence
      rates of breast cancer; intermediate levels were reported in Western Europe,
      Oceania, Scandinavia, and Israel; and Eastern Europe, South and Latin America,
      and Asia had the lowest levels. Breast cancer incidence rose 30-40% from the
      1970s to the 1990s in most countries, with the most marked increases among women
      aged > or =50 years. Mortality from breast cancer paralleled incidence: it was
      highest in the countries with the highest incidence rates (between 17/100,000 and
      27/100,000), lowest in Latin America and Asia (7-14/100,000), and rose most
      rapidly in countries with the lowest rates. CONCLUSIONS: Breast cancer incidence
      and mortality rates remain highest in developed countries compared with
      developing countries, as a result of differential use of screening mammograms and
      disparities in lifestyle and hereditary factors. Future studies assessing the
      combined contributions of both environmental and hereditary factors may provide
      explanations for worldwide differences in incidence and mortality rates.

PMID- 15737978
TI  - Socioeconomic differences in the prevalence of common chronic diseases: an
      overview of eight European countries.
AB  - BACKGROUND: Few studies have compared socioeconomic inequalities in the
      prevalence of both fatal and non-fatal diseases. This paper aims to give the
      first international overview for several common chronic diseases. METHODS: Micro
      level data were pooled from non-standardized national health surveys conducted in
      eight European countries in the 1990s. Surveys ranged in size from 3700 to 41 200
      participants. The prevalence of 17 chronic disease groups were analysed in
      relation to education. Standardized prevalence rates and age-adjusted odds ratios
      (ORs) were calculated. RESULTS: Most diseases showed higher prevalence among the
      lower education group. Stroke, diseases of the nervous system, diabetes, and
      arthritis displayed relatively large inequalities (OR > 1.50). No socioeconomic
      differences were evident for cancer, kidney diseases, and skin diseases. Allergy
      was more common in the higher education group. Relative socioeconomic differences
      were often smaller among the 60-79 age group as compared with the 25-59 age
      group. Cancer was more prevalent among the lower educated in the 25-59 age group,
      but among the higher educated in the 60-79 age group. For diabetes, hypertension,
      and heart disease, socioeconomic differences were larger among women as compared
      with men. Inequalities in heart disease were larger in northern European
      countries as compared with southern European countries. CONCLUSION: There are
      large variations between chronic diseases in the size and pattern of
      socioeconomic differences in their prevalence. The large inequalities that are
      found for some specific fatal diseases (e.g. stroke) and non-fatal diseases (e.g.
      arthritis) require special attention in equity-oriented research and policies.

PMID- 15737979
TI  - Who is more likely to experience common disorders: men, women, or both equally?
      Lay perceptions in the West of Scotland.
AB  - BACKGROUND: Gender differences in health are commonly observed by
      epidemiologists. Little is known about lay beliefs concerning the gender
      patterning of common conditions. METHODS: Using the West of Scotland Twenty-07
      Study, we analysed responses to a question in a postal questionnaire asking
      whether respondents thought men or women (or both equally) were more likely to
      have heart disease, cancer, mental illness, and accidents, to be fit, and to live
      longer. This question was answered by 466 females and 353 males, then aged 25,
      45, and 65 yr. RESULTS: Responses were in general in accord with epidemiological
      findings, but females had significantly lower odds than males of perceiving men
      as being at greater risk of accidents and heart disease, and higher odds than
      males of perceiving women as being at greater risk of mental illness.
      CONCLUSIONS: There was a tendency for each gender to think risks were higher for
      their own sex than did the other gender. This observation needs further
      exploration, particularly in the light of the research showing 'optimistic bias'
      in relation to health, and research suggesting that socioeconomically
      disadvantaged people may be least likely to perceive socially structured health
      inequalities.

PMID- 15737980
TI  - Characterization and functional investigation of an Arabidopsis cDNA encoding a
      homologue to the d-PGMase superfamily.
AB  - An Arabidopsis thaliana cDNA (At-74) has been isolated that encoded an
      uncharacterized protein showing homology with members of the d-PGMase
      superfamily: cofactor-dependent phosphoglycerate mutases (d-PGM-ases) and the
      phosphatase domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases
      (6PF2Kase/F2, 6Pase). Preliminary phylogenetic studies indicated that At-74 cDNA
      and its close homologue in Arabidopsis, At-74H, belong, however, to an equally
      distinct group. At-74 was ubiquitously expressed in vegetative organs and induced
      by glucose. The At-74 cDNA was overexpressed in A. thaliana to investigate its
      function, but this overexpression did not result in a clear phenotype. Enzymatic
      assays performed on At-74-overproducing transgenic plants or E. coli cells showed
      no increase in either the activities of cofactor-dependent and -independent
      phosphoglycerate mutases (i-PGMases) and F2,6Pase or that of acid phosphatases.
      The possible role of At-74 in plant metabolism was further investigated by carbon
      partitioning experiments with [U-(14)C] glucose and measurements of soluble
      sugars in both young leaves and roots. Two overexpressing At-74 lines showed a
      clear increase in glucose uptake. This paper introduces the At-74 homologue of
      the d-PGMase superfamily members and supports a possible role of At-74 in
      carbohydrate metabolism.

PMID- 15737981
TI  - Ectopic endoreduplication caused by sterol alteration results in serrated petals
      in Arabidopsis.
AB  - The Arabidopsis frill1 (frl1) mutant, that has serrated petals and sepals but no
      other large changes in plant morphology, was studied. The frl1 had a mutation in
      STEROL METHYLTRANSFERASE 2 and an altered sterol composition. It was found that
      the frl1 mutation causes ectopic endoreduplication in petal tips that do not
      normally endoreduplicate. The rosette leaves of frl1 also showed an enhanced
      level of endoreduplication, but their morphology was hardly affected. These facts
      suggest that the suppression of endoreduplication is important for petal
      morphogenesis and the normal sterol composition is required for this suppression.

PMID- 15737982
TI  - Purification, molecular cloning, and cell-specific gene expression of the
      alkaloid-accumulation associated protein CrPS in Catharanthus roseus.
AB  - Identification of molecular markers of monoterpenoid indole alkaloid (MIA)
      accumulation in cell-suspension cultures of Madagascar periwinkle (Catharanthus
      roseus (L.) G. Don) was performed by two-dimensional polyacrylamide gel
      electrophoresis. Comparison of the protein patterns from alkaloid-producing and
      non-producing cells showed the specific occurrence of a 28 kDa polypeptide
      restricted to cells accumulating MIAs. The polypeptide was purified by
      preparative two-dimensional gel electrophoresis, digested with trypsin, and
      microsequenced by the Edman degradation method. Cloning of the corresponding cDNA
      revealed that the protein which has been named CrPS (Catharanthus roseus Protein
      S) is a member of the alpha/beta hydrolase superfamily. Time-course expression
      studies by northern blot analysis confirmed that CrPS gene expression was
      associated with MIA accumulation in cell suspension cultures. In the whole plant,
      multicellular compartmentation is required for alkaloid biosynthesis. In situ
      mRNA hybridization on developing leaves revealed that CrPS mRNA and transcripts
      encoding the first enzymes of the MIA pathway were co-localized in internal
      phloem parenchyma cells. The possible implication of the alkaloid-accumulation
      associated protein CrPS in the signal transduction pathway leading to MIA
      production is discussed.

PMID- 15737983
TI  - Root cell patterning: a primary target for aluminium toxicity in maize.
AB  - The short-term influence (5-180 min) of 50 microM Al on cell division was
      investigated in root tips of two Zea mays L. varieties differing in Al
      resistance. The incorporation of bromodeoxyuridine into S-phase nuclei was
      visualized by immunofluorescence staining using confocal laser fluorescence
      microscopy. In Al-sensitive plants 5 min Al exposure was enough to inhibit cell
      division in the proximal meristem (250-800 microm from the tip). After 10 or 30
      min with Al only, a few S-phase nuclei were found in the cortical initials. By
      contrast, cell division was stimulated in the distal elongation zone (2.5-3.1
      mm). After 180 min the protrusion of an incipient lateral root was observed in
      this zone. These observations suggest a fast change in cell patterning rather
      than a general cariotoxic effect after exposure to Al for a short time. No such
      changes were found in Al-resistant maize. This is the first report showing such
      fast Al-induced alterations in the number and the position of dividing cells in
      root tips. The observation that similar changes were induced by a local supply of
      naphthylphthalamic acid to the distal transition zone suggests that inhibition of
      auxin transport plays a role in the Al-induced alteration of root cell
      patterning.

PMID- 15737984
TI  - Aluminium resistance requires resistance to acid stress: a case study with
      spinach that exudes oxalate rapidly when exposed to Al stress.
AB  - Spinach is a vegetable with a high oxalate concentration in its tissues. Oxalate
      efflux from spinach (Spinacia oleracea L. cv. Quanneng) roots was rapidly
      stimulated (within 30 min) by aluminium (Al) treatment. The efflux was constant
      within 6 h, but increased with increasing Al concentration. The efflux was
      confined to the root tip (0-5 mm), which showed a 5-fold greater efflux than the
      root zone distal to the tip (5-10 mm). Oxalate efflux could not be triggered by
      treatment with the trivalent cation lanthanum or by phosphorus deficiency,
      indicating that the efflux was specific to the Al treatment. All this evidence
      suggested that spinach possesses Al-resistance mechanisms. However, spinach was
      found to be as sensitive to Al toxicity as the Al-sensitive wheat line ES8, which
      had no Al-dependent organic acids efflux. The Al accumulated in the apical 5 mm
      of the roots of spinach which was also similar to that in the Al-sensitive wheat
      after 24 h treatment with 50 microM AlCl(3), indicating a non-exclusion
      mechanism. In addition, root elongation in spinach was significantly inhibited at
      pH 4.5, compared with that at pH 6.5. Based on this evidence, it is concluded
      that the sensitivity to acid stress in spinach could mask the potential role for
      oxalate to protect the plant roots from Al toxicity.

PMID- 15737985
TI  - Molecular monitoring of tumour load kinetics predicts disease progression after
      non-myeloablative allogeneic stem cell transplantation in multiple myeloma.
AB  - BACKGROUND: Non-myeloablative allogeneic stem cell transplantation followed by
      immunomodulatory therapies is considered a potentially curative approach in the
      treatment of multiple myeloma and most effective in a minimal residual disease
      setting. PATIENTS AND METHODS: The aim of this study was to find the most
      sensitive real-time PCR assay (TaqMan), based on the IGH rearrangement, to
      quantify the tumour load of 11 patients with multiple myeloma after non
      myeloablative allogeneic transplantation. Patient-allele specific primers (ASO)
      and the TaqMan probe were derived from CDR2 and CDR3 hypervariable regions of
      IGH, while consensus primers were located within the FR3 and FR4/JH regions. Four
      different approaches of primer combinations were tested. RESULTS: ASO-forward and
      -reverse primers together with the clone-specific TaqMan probe were the most
      sensitive approach compared with the JH (P=0.071) or the FR3 consensus primer (P
      <0.001). The detection limit amounted to 1/10(4)-1/10(5) cells. Consecutively,
      120 samples from 11 patients prior and post allogeneic transplantation were
      analysed. Three patients reached complete clinical remission accompanied by
      molecular remission. Disease progression or relapse was seen in six patients. In
      five, molecular progressive disease was detected prior to the clinical diagnosis
      of progression or relapse. CONCLUSION: Patient-specific real-time IGH-PCR
      provides the opportunity for earlier treatment intervention.

PMID- 15737986
TI  - Prognostic factors affecting long-term outcome after stem cell transplantation in
      Hodgkin's lymphoma autografted after a first relapse.
AB  - PURPOSE: To analyse outcome and prognostic factors for overall survival (OS) and
      time to treatment failure (TTF) in 357 patients with Hodgkin's lymphoma (HL)
      undergoing an autologous stem cell transplantation (ASCT) after a first relapse
      and reported to the The Grupo Espanol de Linfomas/Trasplante Autologo de Medula
      Osea (GEL/TAMO) Cooperative Group. METHODS: Two hundred and twenty males and 137
      females with a median age of 29 years were autografted in second remission
      (n=181), first sensitive relapse (n=148) and first resistant relapse (n=28).
      RESULTS: Five-year actuarial TTF and OS were of 49% +/- 3% and 57% +/- 3%.
      Advanced stage at diagnosis, complementary radiotherapy before ASCT, a short
      first complete response (CR) and detectable disease at ASCT adversely influenced
      TTF. Year of transplant < or =1995, bulky disease at diagnosis, a short first CR,
      detectable disease at ASCT and > or =1 extranodal areas involved at ASCT were
      adverse factors for OS. CONCLUSIONS: ASCT constitutes a therapeutic option for HL
      patients after a first relapse. Promising results are observed in patients with
      low tumour burden at diagnosis, autografted after a long CR and without
      detectable disease at ASCT. Innovative approaches should be pursued for patients
      with risk factors at relapse.

PMID- 15737987
TI  - A hepatocyte nuclear factor-3 site in the fibrinogen beta promoter is important
      for interleukin 6-induced expression, and its activity is influenced by the
      adjacent -148C/T polymorphism.
AB  - An elevated plasma fibrinogen level is an independent risk factor for
      cardiovascular disease. Therefore, an understanding of the regulation of
      fibrinogen expression is important. Inflammation and genetic variation of the
      fibrinogen beta gene regulate plasma fibrinogen levels, and there are indications
      that inflammation and genetic variation interact. The aim of our study was to
      gain more understanding of the regulation of the inflammatory response of the
      fibrinogen beta gene and to determine the effects of genetic variation.
      Luciferase reporter gene assays in hepatoma cells, mutation analysis, and
      electrophoretic mobility shift assays were used to investigate the
      transcriptional regulation of the fibrinogen beta promoter. We identified a
      hepatocyte nuclear factor-3 (HNF-3) site located just upstream of previously
      identified interleukin-6 (IL6)-responsive sequences. This HNF-3 site is essential
      for a full response of the promoter to IL6, which is a new function for HNF-3.
      The activity of the CCAAT box/enhancer-binding protein site (located 18
      nucleotides downstream of the HNF-3 site and important to the IL6 response)
      depends on the integrity of the HNF-3 site and vice versa, explaining the
      necessity of HNF-3 in the IL6 response of the fibrinogen beta promoter.
      Furthermore, small interfering RNA to HNF-3 reduces the fibrinogen beta mRNA
      levels. The rare T allele of the -148C/T polymorphism, which is present between
      the binding sites of HNF-3 and CCAAT box/enhancer-binding protein, interferes
      with this mechanism, and this polymorphism is in our assay system the only
      genetic determinant of IL6-induced promoter activity among six polymorphisms in
      the fibrinogen beta promoter.

PMID- 15737988
TI  - Borrelia burgdorferi binds fibronectin through a tandem beta-zipper, a common
      mechanism of fibronectin binding in staphylococci, streptococci, and spirochetes.
AB  - BBK32 is a fibronectin-binding protein from the Lyme disease-causing spirochete
      Borrelia burgdorferi. In this study, we show that BBK32 shares sequence
      similarity with fibronectin module-binding motifs previously identified in
      proteins from Streptococcus pyogenes and Staphylococcus aureus. Nuclear magnetic
      resonance spectroscopy and isothermal titration calorimetry are used to confirm
      the binding sites of BBK32 peptides within the N-terminal domain of fibronectin
      and to measure the affinities of the interactions. Comparison of chemical shift
      perturbations in fibronectin F1 modules on binding of peptides from BBK32, FnBPA
      from S. aureus, and SfbI from S. pyogenes provides further evidence for a shared
      mechanism of binding. Despite the different locations of the bacterial attachment
      sites in BBK32 compared with SfbI from S. pyogenes and FnBPA from S. aureus, an
      antiparallel orientation is observed for binding of the N-terminal domain of
      fibronectin to each of the pathogens. Thus, these phylogenetically and
      morphologically distinct bacterial pathogens have similar mechanisms for binding
      to human fibronectin.

PMID- 15737989
TI  - A serine/threonine-rich motif is one of three nuclear localization signals that
      determine unidirectional transport of the mineralocorticoid receptor to the
      nucleus.
AB  - The mineralocorticoid receptor (MR) is a tightly regulated nuclear hormone
      receptor that selectively transmits corticosteroid signals. Steroid treatment
      transforms MR from a transcriptionally inert state, in which it is distributed
      equally between the nucleus and cytoplasm, to an active completely nuclear
      transcription factor. We report here that MR is an atypical nuclear hormone
      receptor that moves unidirectionally from the cytoplasm to the nucleus. We show
      that nuclear import of MR is controlled through three nuclear localization
      signals (NLSs) of distinct types. Nuclear localization of naive MR was mediated
      primarily through a novel serine/threonine-rich NLS (NL0) in the receptor N
      terminus. Specific amino acid substitutions that mimicked phosphorylation
      selectively enhanced or repressed NL0 activity, highlighting the potential for
      active regulation of this new type of NLS. The second NLS (NL2) within the ligand
      binding domain also lacks a recognizable basic motif. Nuclear transfer through
      this signal was strictly dependent on steroid agonist, but was independent of the
      interaction of MR with coactivator proteins. The third MR NLS (NL1) is a
      bipartite basic motif localized to the C terminus of the MR DNA-binding domain
      with properties distinct from those of NL1 of the closely related glucocorticoid
      receptor. NL1 acted in concert with NL0 and NL2 to stimulate nuclear uptake of
      the agonist-treated receptor, but also directed the complete nuclear localization
      of MR in response to treatment with steroid antagonist. These results present MR
      as a nuclear hormone receptor whose unidirectional transfer to the nucleus may be
      regulated through multiple pathways.

PMID- 15737990
TI  - Parkin stabilizes microtubules through strong binding mediated by three
      independent domains.
AB  - Mutations of parkin, a protein-ubiquitin isopeptide ligase (E3), appear to be the
      most frequent cause of familial Parkinson's disease (PD). Our previous studies
      have demonstrated that parkin binds strongly to alpha/beta tubulin heterodimers
      and microtubules. Here we show that the strong binding between parkin and
      tubulin, as well as that between parkin and microtubules, was mediated by three
      independent domains: linker, RING1, and RING2. These redundant strong
      interactions made it virtually impossible to separate parkin from microtubules by
      high concentrations of salt (3.8 m) or urea (0.5 m). Parkin co-purified with
      tubulin and was found in highly purified tubulin preparation. Expression of
      either full-length parkin or any of its three microtubule-binding domains
      significantly attenuated colchicine-induced microtubule depolymerization. The
      abilities of parkin to bind to and stabilize microtubules were not affected by PD
      linked mutations that abrogate its E3 ligase activity. Thus, the
      tubulin/microtubule-binding activity of parkin and its E3 ligase activity are
      independent. The strong binding between parkin and tubulin/microtubules through
      three redundant interaction domains may not only stabilize microtubules but also
      guarantee the anchorage of this E3 ligase on microtubules. Because many misfolded
      proteins are transported on microtubules, the localization of parkin on
      microtubules may provide an important environment for its E3 ligase activity
      toward misfolded substrates.

PMID- 15737991
TI  - Ion regulation of homotypic vacuole fusion in Saccharomyces cerevisiae.
AB  - Biological membrane fusion employs divalent cations as protein cofactors or as
      signaling ligands. For example, Mg2+ is a cofactor for the N-ethylmaleimide
      sensitive factor (NSF) ATPase, and the Ca2+ signal from neuronal membrane
      depolarization is required for synaptotagmin activation. Divalent cations also
      regulate liposome fusion, but the role of such ion interactions with lipid
      bilayers in Rab- and soluble NSF attachment protein receptor (SNARE)-dependent
      biological membrane fusion is less clear. Yeast vacuole fusion requires Mg2+ for
      Sec18p ATPase activity, and vacuole docking triggers an efflux of luminal Ca2+.
      We now report distinct reaction conditions where divalent or monovalent ions
      interchangeably regulate Rab- and SNARE-dependent vacuole fusion. In reactions
      with 5 mm Mg2+, other free divalent ions are not needed. Reactions containing low
      Mg2+ concentrations are strongly inhibited by the rapid Ca2+ chelator BAPTA.
      However, addition of the soluble SNARE Vam7p relieves BAPTA inhibition as
      effectively as Ca2+ or Mg2+, suggesting that Ca2+ does not perform a unique
      signaling function. When the need for Mg2+, ATP, and Sec18p for fusion is
      bypassed through the addition of Vam7p, vacuole fusion does not require any
      appreciable free divalent cations and can even be stimulated by their chelators.
      The similarity of these findings to those with liposomes, and the higher ion
      specificity of the regulation of proteins, suggests a working model in which ion
      interactions with bilayer lipids permit Rab- and SNARE-dependent membrane fusion.

PMID- 15737992
TI  - Structural characterization of a novel Cbl phosphotyrosine recognition motif in
      the APS family of adapter proteins.
AB  - The Cbl adapter proteins typically function to down-regulate activated protein
      tyrosine kinases and other signaling proteins by coupling them to the
      ubiquitination machinery for degradation by the proteasome. Cbl proteins bind to
      specific tyrosine-phosphorylated sequences in target proteins via the tyrosine
      kinase-binding (TKB) domain, which comprises a four-helix bundle, an EF-hand
      calcium-binding domain, and a non-conventional Src homology-2 domain. The
      previously derived consensus sequence for phosphotyrosine recognition by the Cbl
      TKB domain is NXpY(S/T)XXP (X denotes lesser residue preference), wherein
      specificity is conferred primarily by residues C-terminal to the phosphotyrosine.
      Cbl is recruited to and phosphorylated by the insulin receptor in adipose cells
      through the adapter protein APS. APS is phosphorylated by the insulin receptor on
      a C-terminal tyrosine residue, which then serves as a binding site for the Cbl
      TKB domain. Using x-ray crystallography, site-directed mutagenesis, and
      calorimetric studies, we have characterized the interaction between the Cbl TKB
      domain and the Cbl recruitment site in APS, which contains a sequence motif,
      RA(V/I)XNQpY(S/T), that is conserved in the related adapter proteins SH2-B and
      Lnk. These studies reveal a novel mode of phosphopeptide interaction with the Cbl
      TKB domain, in which N-terminal residues distal to the phosphotyrosine directly
      contact residues of the four-helix bundle of the TKB domain.

PMID- 15737993
TI  - Distinct poly(I-C) and virus-activated signaling pathways leading to interferon
      beta production in hepatocytes.
AB  - Innate cellular antiviral defenses are likely to influence the outcome of
      infections by many human viruses, including hepatitis B and C viruses, agents
      that frequently establish persistent infection leading to chronic hepatitis,
      cirrhosis, and liver cancer. However, little is known of the pathways by which
      hepatocytes, the cell type within which these hepatitis agents replicate, sense
      infection, and initiate protective responses. We show that cultured hepatoma
      cells, including Huh7 cells, do not activate the interferon (IFN)-beta promoter
      in response to extracellular poly(I-C). In contrast, the addition of poly(I-C) to
      culture media activates the IFN-beta promoter and results in robust expression of
      IFN-stimulated genes (ISG) in PH5CH8 cells, which are derived from non-neoplastic
      hepatocytes transformed with large T antigen. Small interfering RNA knockdown of
      TLR3 or its adaptor, Toll-interleukin-1 receptor domain-containing adaptor
      inducing IFN-beta (TRIF), blocked extracellular poly(I-C) signaling in PH5CH8
      cells, whereas poly(I-C) responsiveness could be conferred on Huh7 hepatoma cells
      by ectopic expression of Toll-like receptor 3 (TLR3). In contrast to poly(I-C),
      both cell types signal the presence of Sendai virus infection through a TLR3
      independent intracellular pathway requiring expression of retinoic acid-inducible
      gene I (RIG-I), a putative cellular RNA helicase. Silencing of RIG-I expression
      impaired only the response to Sendai virus and not extracellular poly(I-C). We
      conclude that hepatocytes contain two distinct antiviral signaling pathways
      leading to expression of type I IFNs, one dependent upon TLR3 and the other
      dependent on RIG-I, with little cross-talk between these pathways.

PMID- 15737994
TI  - Cyclin A is a c-Jun target gene and is necessary for c-Jun-induced anchorage
      independent growth in RAT1a cells.
AB  - Overexpression of c-Jun enables Rat1a cells to grow in an anchorage-independent
      manner. We used an inducible c-Jun system under the regulation of doxycycline in
      Rat1a cells to identify potential c-Jun target genes necessary for c-Jun-induced
      anchorage-independent growth. Induction of c-Jun results in sustained expression
      of cyclin A in the nonadherent state with only minimal expression in the absence
      of c-Jun. The promoter activity of cyclin A2 was 4-fold higher in Rat1a cells in
      which c-Jun expression was induced compared with the control cells. Chromatin
      immunoprecipitation demonstrated that c-Jun bound directly to the cyclin A2
      promoter. Mutation analysis of the cyclin A2 promoter mapped the c-Jun regulatory
      site to an ATF site at position -80. c-Jun was able to bind to this site both in
      vitro and in vivo, and mutation of this site completely abolished promoter
      activity. Cyclin A1 was also elevated in c-Jun-overexpressing Rat1a cells;
      however, c-Jun did not regulate this gene directly, since it did not bind
      directly to the cyclin A1 promoter. Suppression of cyclin A expression via the
      introduction of a cyclin A antisense sequences significantly reduced the ability
      of c-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion.
      Taken together, these results suggest that cyclin A is a target of c-Jun and is
      necessary but not sufficient for c-Jun-induced anchorage-independent growth. In
      addition, we demonstrated that the cytoplasmic oncogenes Ras and Src
      transcriptionally activated the cyclin A2 promoter via the ATF site at position 
      80. Using a dominant negative c-Jun mutant, TAM67, we showed that this
      transcriptional activation of cyclin A2 requires c-Jun. Thus, our results suggest
      that c-Jun is a mediator of the aberrant cyclin A2 expression associated with
      Ras/Src-induced transformation.

PMID- 15737995
TI  - Roles of 3-phosphoinositide-dependent kinase 1 in the regulation of endothelial
      nitric-oxide synthase phosphorylation and function by heat shock protein 90.
AB  - The 90-kDa heat shock protein (Hsp90) plays an important role in endothelial
      nitric-oxide synthase (eNOS) regulation. Besides acting as an allosteric
      enhancer, Hsp90 was shown to serve as a module recruiting Akt to phosphorylate
      the serine 1179/1177 (bovine/human) residue of eNOS. Akt is activated by the
      phosphorylation of 3-phosphoinositide-dependent kinase 1 (PDK1). Whether PDK1 is
      involved in the actions of Hsp90 on eNOS phosphorylation and function remains
      unknown. To address this issue, we treated bovine eNOS stably transfected human
      embryonic kidney 293 cells with Hsp90 inhibitors and determined the alterations
      of phospho-eNOS, Akt, and PDK1. Both geldanamycin and radicicol, two structurally
      different Hsp90 inhibitors, selectively reduced serine 1179-phosphorylated eNOS,
      leading to decreased enzyme activity. In Hsp90-inhibited cells, eNOS-associated
      phospho-Akt was decreased, but the total amount of Akt associated with eNOS
      remained the same. Further studies showed that Hsp90 inhibition dramatically
      depleted intracellular PDK1. Proteasome but not caspase blockade prevented the
      loss of PDK1 caused by Hsp90 inhibition. Silencing the PDK1 gene by small
      interfering RNA was sufficient to induce reduction of phospho-Akt and consequent
      loss of serine 1179-phosphorylated eNOS. Moreover, overexpression of PDK1, but
      not Akt, reversed Hsp90 inhibition-induced loss of eNOS serine 1179
      phosphorylation and salvaged enzymatic activity. Thus, in addition to functioning
      as a module to recruit Akt to eNOS, Hsp90 also critically stabilized PDK1 by
      preventing it from proteasomal degradation. Inhibition of Hsp90 function resulted
      in PDK1 depletion and thus triggered a cascade of Akt deactivation, loss of eNOS
      serine 1179 phosphorylation, and decrease of enzyme function.

PMID- 15737996
TI  - Regulation of poly(ADP-ribose) polymerase-1 by DNA structure-specific binding.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is an intracellular sensor of DNA strand
      breaks and plays a critical role in cellular responses to DNA damage. In normally
      functioning cells, PARP-1 enzymatic activity has been linked to the alterations
      in chromatin structure associated with gene expression. However, the molecular
      determinants for PARP-1 recruitment to specific sites in chromatin in the absence
      of DNA strand breaks remain obscure. Using gel shift and enzymatic footprinting
      assays and atomic force microscopy, we show that PARP-1 recognizes distortions in
      the DNA helical backbone and that it binds to three- and four-way junctions as
      well as to stably unpaired regions in double-stranded DNA. PARP-1 interactions
      with non-B DNA structures are functional and lead to its catalytic activation.
      DNA hairpins, cruciforms, and stably unpaired regions are all effective co
      activators of PARP-1 auto-modification and poly(ADP-ribosyl)ation of histone H1
      in the absence of free DNA ends. Enzyme kinetic analyses revealed that the
      structural features of non-B form DNA co-factors are important for PARP-1
      catalysis activated by undamaged DNA. K0.5 constants for DNA co-factors, which
      are structurally different in the degree of base pairing and spatial DNA
      organization, follow the order: cruciform<or=hairpin<<loop. DNA structure also
      influenced the reaction rate; when a hairpin was substituted with a stably
      unpaired region, the maximum reaction velocity decreased almost 2-fold. These
      data suggest a link between PARP-1 binding to non-B DNA structures in genome and
      its function in the dynamics of local modulation of chromatin structure in the
      normal physiology of the cell.

PMID- 15737997
TI  - Complete inhibition of anisomycin and UV radiation but not cytokine induced JNK
      and p38 activation by an aryl-substituted dihydropyrrolopyrazole quinoline and
      mixed lineage kinase 7 small interfering RNA.
AB  - Mixed lineage kinase 7 (MLK7) is a mitogen-activated protein kinase kinase kinase
      (MAPKKK) that activates the pro-apoptotic signaling pathways p38 and JNK. A
      library of potential kinase inhibitors was screened, and a series of
      dihydropyrrolopyrazole quinolines was identified as highly potent inhibitors of
      MLK7 in vitro catalytic activity. Of this series, an aryl-substituted
      dihydropyrrolopyrazole quinoline (DHP-2) demonstrated an IC50 of 70 nM for
      inhibition of pJNK formation in COS-7 cell MLK7/JNK co-transfection assays. In
      stimulated cells, DHP-2 at 200 nM or MLK7 small interfering RNA completely
      blocked anisomycin and UV induced but had no effect on interleukin-1beta or tumor
      necrosis factor-alpha-induced p38 and JNK activation. Additionally, the compound
      blocked anisomycin and UV-induced apoptosis in COS-7 cells. Heart tissue
      homogenates from MLK7 transgenic mice treated with DHP-2 at 30 mg/kg had reduced
      JNK and p38 activation with no apparent effect on ERK activation, demonstrating
      that this compound can be used to block MLK7-driven MAPK pathway activation in
      vivo. Taken together, these data demonstrate that MLK7 is the MAPKKK required for
      modulation of the stress-activated MAPKs downstream of anisomycin and UV
      stimulation and that DHP-2 can be used to block MLK7 pathway activation in cells
      as well as in vivo.

PMID- 15737998
TI  - Purified recombinant hypothetical protein coded by open reading frame Rv1885c of
      Mycobacterium tuberculosis exhibits a monofunctional AroQ class of periplasmic
      chorismate mutase activity.
AB  - Naturally occurring variants of the enzyme chorismate mutase are known to exist
      that exhibit diversity in enzyme structure, regulatory properties, and
      association with other proteins. Chorismate mutase was not annotated in the
      initial genome sequence of Mycobacterium tuberculosis (Mtb) because of low
      sequence similarity between known chorismate mutases. Recombinant protein coded
      by open reading frame Rv1885c of Mtb exhibited chorismate mutase activity in
      vitro. Biochemical and biophysical characterization of the recombinant protein
      suggests its resemblance to the AroQ class of chorismate mutases, prototype
      examples of which include the Escherichia coli and yeast chorismate mutases. We
      also demonstrate that unlike the corresponding proteins of E. coli, Mtb
      chorismate mutase does not have any associated prephenate dehydratase or
      dehydrogenase activity, indicating its monofunctional nature. The Rv1885c-encoded
      chorismate mutase showed allosteric regulation by pathway-specific as well as
      cross-pathway-specific ligands, as evident from proteolytic cleavage protection
      and enzyme assays. The predicted N-terminal signal sequence of Mtb chorismate
      mutase was capable of functioning as one in E. coli, suggesting that Mtb
      chorismate mutase belongs to the AroQ class of chorismate mutases. It was evident
      that Rv1885c may not be the only enzyme with chorismate mutase enzyme function
      within Mtb, based on our observation of the presence of chorismate mutase
      activity displayed by another hypothetical protein coded by open reading frame
      Rv0948c, a novel instance of the existence of two monofunctional chorismate
      mutases ever reported in any pathogenic bacterium.

PMID- 15737999
TI  - Identification and characterization of a novel plastidic adenine nucleotide
      uniporter from Solanum tuberosum.
AB  - Homologs of BT1 (the Brittle1 protein) are found to be phylogenetically related
      to the mitochondrial carrier family and appear to occur in both mono- and
      dicotyledonous plants. Whereas BT1 from cereals is probably involved in the
      transport of ADP-glucose, which is essential for starch metabolism in endosperm
      plastids, BT1 from a noncereal plant, Solanum tuberosum (StBT1), catalyzes an
      adenine nucleotide uniport when functionally integrated into the bacterial
      cytoplasmic membrane. Import studies into intact Escherichia coli cells harboring
      StBT1 revealed a narrow substrate spectrum with similar affinities for AMP, ADP,
      and ATP of about 300-400 mum. Transiently expressed StBT1-green fluorescent
      protein fusion protein in tobacco leaf protoplasts showed a plastidic
      localization of the StBT1. In vitro synthesized radioactively labeled StBT1 was
      targeted to the envelope membranes of isolated spinach chloroplasts. Furthermore,
      we showed by real time reverse transcription-PCR a ubiquitous expression pattern
      of the StBT1 in autotrophic and heterotrophic potato tissues. We therefore
      propose that StBT1 is a plastidic adenine nucleotide uniporter used to provide
      the cytosol and other compartments with adenine nucleotides exclusively
      synthesized inside plastids.

PMID- 15738000
TI  - Direct interaction of Rnd1 with FRS2 beta regulates Rnd1-induced down-regulation
      of RhoA activity and is involved in fibroblast growth factor-induced neurite
      outgrowth in PC12 cells.
AB  - The Rho family of small GTPases has been implicated in the reorganization of the
      actin cytoskeleton and subsequent morphological changes in various cells. Rnd1, a
      member of this family, has a low intrinsic GTPase activity and exerts
      antagonistic effects on RhoA signaling. However, how the activity of Rnd1 is
      regulated has not yet been elucidated. Here we have demonstrated that Rnd1
      directly associates with FRS2alpha and FRS2beta, which are docking proteins of
      fibroblast growth factor (FGF) receptors and play important roles in the
      intracellular signals induced by FGFs. The interaction of FRS2beta with Rnd1
      suppresses the inhibitory effect of Rnd1 on RhoA. Rnd1 binds to the COOH-terminal
      region of FRS2beta including tyrosine residues essential for the interaction with
      Shp2. When FGF receptor 1 is activated, it phosphorylates FRS2beta, recruits
      Shp2, and releases Rnd1 from FRS2beta. The liberated Rnd1 then inhibits RhoA
      activity. Furthermore, knockdown of Rnd1 by Rnd1-specific short interfering RNAs
      suppress the FGF-induced neurite outgrowth in PC12 cells. These results suggest
      that the activity of Rnd1 is regulated by FGF receptor through FRS2beta and that
      Rnd1 plays an important role in the FGF signaling during neurite outgrowth.

PMID- 15738001
TI  - Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells
      at G2 phase of cell cycle in a p53-dependent manner.
AB  - Curcumin (diferuloylmethane) is known to induce apoptosis in tumor cells. In
      asynchronous cultures, with time-lapse video-micrography in combination with
      quantitative fluorescence microscopy, we have demonstrated that curcumin induces
      apoptosis at G(2) phase of cell cycle in deregulated cyclin D1-expressed mammary
      epithelial carcinoma cells, leaving its normal counterpart unaffected. In our
      search toward delineating the molecular mechanisms behind such differential
      activities of curcumin, we found that it selectively increases p53 expression at
      G(2) phase of carcinoma cells and releases cytochrome c from mitochondria, which
      is an essential requirement for apoptosis. Further experiments using p53-null as
      well as dominant-negative and wild-type p53-transfected cells have established
      that curcumin induces apoptosis in carcinoma cells via a p53-dependent pathway.
      On the other hand, curcumin reversibly inhibits normal mammary epithelial cell
      cycle progression by down-regulating cyclin D1 expression and blocking its
      association with Cdk4/Cdk6 as well as by inhibiting phosphorylation and
      inactivation of retinoblastoma protein. In addition, curcumin significantly up
      regulates cell cycle inhibitory protein (p21Waf-1) in normal cells and arrests
      them in G(0) phase of cell cycle. Therefore, these cells escape from curcumin
      induced apoptosis at G(2) phase. Interestingly, these processes remain unaffected
      by curcumin in carcinoma cells where cyclin D1 expression is high. Similarly, in
      ectopically overexpressed system, curcumin cannot down-regulate cyclin D1 and
      thus block cell cycle progression. Hence, these cells progress into G(2) phase
      and undergo apoptosis. These observations together suggest that curcumin may have
      a possible therapeutic potential in breast cancer patients.

PMID- 15738002
TI  - Inhibition of p90 ribosomal S6 kinase-mediated CCAAT/enhancer-binding protein
      beta activation and cyclooxygenase-2 expression by salicylate.
AB  - We have previously shown that salicylate at a pharmacological concentration
      suppresses CCAAT/enhancer-binding protein beta (C/EBPbeta) binding, thereby
      reducing cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase expression
      (Saunders, M. A., Sansores-Garcia, L., Gilroy, D. W., and Wu, K. K. (2001) J.
      Biol. Chem. 276, 18897-18904; Cieslik, K., Zhu, Y., and Wu, K. K. (2002) J. Biol.
      Chem. 277, 49304-49310). We postulated that salicylate targets a kinase that
      phosphorylates and activates C/EBPbeta. Here we report the identification of p90
      ribosomal S6 kinase (RSK) as a target of salicylate. Salicylate inhibited RSK in
      vivo and blocked the activity of RSK2 purified from cells stimulated by phorbol
      12-myristate 13-acetate (PMA). Mutation of the RSK-phosphorylation site (T266A)
      of C/EBPbeta abrogated PMA-stimulated C/EBPbeta binding activity. RSK activation
      was required for PMA-induced COX-2 transcriptional activation. Salicylate also
      inhibited Ras and extracellular signal-regulated kinase (ERK) activation induced
      by PMA. We conclude that salicylate inhibits C/EBPbeta-mediated COX-2
      transcriptional activation by blocking RSK activity and Ras signaling pathway.

PMID- 15738003
TI  - Expression of constitutively active Akt/protein kinase B signals GLUT4
      translocation in the absence of an intact actin cytoskeleton.
AB  - The actin cytoskeleton has been shown to be required for insulin-dependent GLUT4
      translocation; however, the role that the actin network plays is unknown. Actin
      may play a role in formation of an active signaling complex, or actin may be
      required for movement of vesicles to the plasma membrane surface. To distinguish
      between these possibilities, we examined the ability of myr-Akt, a constitutively
      active form of Akt that signals GLUT4 translocation to the plasma membrane in the
      absence of insulin, to signal translocation of an HA-GLUT4-GFP reporter protein
      in the presence or absence of an intact cytoskeleton in 3T3-L1 adipocytes.
      Expression of myr-Akt signaled the redistribution of the GLUT4 reporter protein
      to the cell surface in the absence or presence of 10 microm latrunculin B, a
      concentration sufficient to completely inhibit insulin-dependent redistribution
      of the GLUT4 reporter to the cell surface. These data suggest that the actin
      network plays a primary role in organization of the insulin-signaling complex. To
      further support this conclusion, we measured the activation of known signaling
      proteins using a saturating concentration of insulin in cells pretreated without
      or with 10 microm latrunculin B. We found that latrunculin treatment did not
      affect insulin-dependent tyrosine phosphorylation of the insulin receptor beta
      subunit and IRS-1 but completely inhibited activation of Akt/PKB enzymatic
      activity. Phosphorylation of Akt/PKB at Ser-473 and Thr-308 was inhibited by
      latrunculin B treatment, indicating that the defect in signaling lies prior to
      Akt/PKB activation. In summary, our data support the hypothesis that the actin
      network plays a role in organization of the insulin-signaling complex but is not
      required for vesicle trafficking and/or fusion.

PMID- 15738004
TI  - Green tea extract and (-)-epigallocatechin-3-gallate, the major tea catechin,
      exert oxidant but lack antioxidant activities.
AB  - Green tea is the most widely consumed beverage. It has attained high reputation
      as a health-promoting dietary component ascribed to the antioxidant activity of (
      )-epigallocatechin-3-gallate (EGCG), its main polyphenolic constituent. Evidence
      is increasing that tea constituents can be cell damaging and pro-oxidant
      themselves. These effects were suggested to be due to spontaneous H2O2 generation
      by polyphenols in solution. In the present study, we investigated the oxidant and
      antioxidant properties of green tea extracts (GTE) and of EGCG by means of the
      rodent macrophage-like RAW 264.7 and human promyelocytic leukemic HL60 cell
      lines. The results obtained show that both under cell-free conditions and in the
      presence of cells the oxidant activities of GTE and EGCG exceeded those of
      spontaneously generated H2O2 (FOX assay). Increase of intracellular oxidative
      stress was indicated by 2',7'-dichlorofluorescin probing, and the enhanced
      genotoxicity was demonstrated by the alkaline comet assay and by the micronucleus
      assay (cytokinesis block). Time- and dose-dependent induction of cell death was
      monitored by trypan blue exclusion, MTT assay, and Hoechst staining. Furthermore,
      in our systems in vitro, EGCG neither directly scavenges H2O2 nor mediates other
      antioxidant activities but rather increased H2O2-induced oxidative stress and DNA
      damage. In conclusion, our data suggest that detailed mechanistic studies on the
      effects of GTE and EGCG should be performed in vivo before excessive intake
      and/or topical application of green tea products can be recommended to healthy
      and/or diseased persons.

PMID- 15738005
TI  - Conditional signaling by Toll-like receptor 4.
AB  - Signaling through Toll-like receptor 4 (TLR4) is thought to initiate innate and
      adaptive immune responses. Signaling of TLR4 is usually studied using isolated
      cells, which are activated by sub-nanomolar concentrations of lipopolysaccharide
      (LPS). However, in normal tissues, cells bearing TLR4 reside in microenvironments
      containing large amounts of endogenous substances that can stimulate the
      receptor. We developed an in vitro model system using the human cell line HEK 293
      and an in vivo model using mice that have normal or that lack TLR4 receptors to
      study how TLR4 functions in such microenvironments. Here we report that signaling
      through TLR4 is strongly inhibited by intact extracellular matrix and that
      inhibition is abrogated and endogenous agonist(s) are liberated when the matrix
      is degraded. Thus, release from inhibition rather than direct stimulation by
      agonists such as LPS is the critical first event by which TLR4 initiates immune
      responses.

PMID- 15738007
TI  - Gestational diabetes mellitus: a pill or a shot?

PMID- 15738008
TI  - Can electronic fetal monitoring identify preterm neonates with cerebral white
      matter injury?
AB  - OBJECTIVE: Although preterm delivery occurs in only 10% of all births, these
      infants are at high risk for cerebral white matter injury and constitute a third
      of all cerebral palsy cases. Our objective was to estimate if electronic
      monitoring can identify preterm fetuses diagnosed with brain injury during the
      neonatal period. METHODS: In this case-control study, 150 consecutive neonates
      with ultrasonography-diagnosed cerebral white matter injury were matched by
      gestational age within 7 days to 150 controls with normal head ultrasonograms.
      Tracings were retrieved for 125 cases (83%) and 121 controls (81%) and reviewed
      by 3 perinatologists blinded to outcome. Vaginal (64 cases, 72 controls) and
      cesarean deliveries (61 cases, 49 controls) were analyzed separately. RESULTS:
      There was no difference in baseline heart rate, tachycardia, bradycardia, short
      term variability, accelerations, reactivity, number or types of decelerations, or
      bradycardic episodes between cases and controls in either the vaginal or cesarean
      delivery groups. For the 6 neonates with metabolic acidosis severe enough to
      increase the risk for long-term neurologic morbidity, there was a significant
      increase in baseline amplitude range less than 5 beats per minute; however, its
      positive predictive value in predicting severe metabolic acidosis was only 7.7%.
      Increasing late decelerations were associated with decreasing umbilical arterial
      pH and base excess, but were not significantly different in the acidosis and
      control groups (1.0 +/- 1.8, 0.55 +/- 1.23 late decelerations per hour, P = .39).
      CONCLUSION: Although decreased short-term variability and increased late
      decelerations are associated with decreasing umbilical arterial pH and base
      excess, electronic fetal monitoring is unable to identify preterm neonates with
      cerebral white matter injury.

PMID- 15738010
TI  - High compared with standard gentamicin dosing for chorioamnionitis: a comparison
      of maternal and fetal serum drug levels.
AB  - OBJECTIVE: To compare umbilical cord and maternal serum peak gentamicin
      concentration, gentamicin elimination, and clinical outcomes between women who
      received once-daily compared with standard, thrice-daily dosing for clinical
      chorioamnionitis. METHODS: We randomly assigned 38 laboring women, at least 34
      weeks gestation, with clinical chorioamnionitis, into 1 of 2 gentamicin dosing
      groups: 5.1 mg/kg every 24 hours (once-daily; n = 18), or 120 mg followed by 80
      mg every 8 hours (standard; n = 20). We measured maternal serum peak and delivery
      gentamicin concentrations and cord serum levels at delivery. Polynomial curve
      fitting was used to summarize gentamicin elimination. We also compared maternal
      and neonatal outcomes. RESULTS: Demographic characteristics of the 2 groups were
      similar. Median maternal peak gentamicin levels were higher with once-daily (18.2
      microg/mL) compared with standard dosing (7.1 microg/mL) (P < .001). Maternal
      serum levels decreased below 2 microg/mL by 10 hours in the once-daily group and
      by 5 hours in the standard dosing group. Extrapolated peak cord serum levels were
      6.9 microg/mL in the once-daily and 2.9 microg/mL in the standard dosing arm.
      Cord levels decreased below 2 microg/mL by 10 hours in the once-daily and by 5
      hours in the standard dosing group. We found no differences in maternal or
      neonatal outcomes. CONCLUSION: Peak maternal serum gentamicin levels ranged from
      13 to 25 microg/mL after a dose of 5.1 mg/kg. Single-dose gentamicin resulted in
      fetal serum peak levels that were closer to optimal neonatal values. Gentamicin
      clearance in the term fetus was similar to published values for the newborn
      infant. No adverse effects of high-dose therapy were noted.

PMID- 15738009
TI  - Outpatient misoprostol compared with dinoprostone gel for preinduction cervical
      ripening: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether a single outpatient dose of intravaginal
      misoprostol (versus intracervical dinoprostone gel) reduces the oxytocin use for
      induction. Despite the numerous trials examining misoprostol for induction, the
      efficacy of a single outpatient dose of misoprostol followed by oxytocin
      induction is unknown. METHODS: Patients with a term, vertex, singleton pregnancy
      and a Bishop score of 6 or less were randomly assigned to receive misoprostol (n
      = 42, 0.25 microg intravaginally) or dinoprostone gel (n = 42, 0.5 mg
      intracervically) the evening before oxytocin induction. Patients were monitored
      for 3 hours after administration and discharged to home if fetal assessment was
      reassuring, for readmission the next morning for oxytocin. Primary outcomes were
      oxytocin dose, time, and dose intensity (dose divided by duration). Secondary
      outcomes were incidence of labor, uterine hyperstimulation, cesarean delivery,
      Apgar score. Statistics used were chi(2), Student t test, Mann-Whitney rank sum
      test, and Fisher exact test. P < .05 was accepted as statistically significant.
      RESULTS: A single dose of misoprostol significantly decreased the cumulative dose
      of oxytocin, the cumulative time of oxytocin administration, and the dose
      intensity of oxytocin (dose divided by time). Data are as follows (mean +/-
      standard error of the mean): oxytocin dose-dinoprostone 10,929 +/- 219 mU,
      misoprostol 6,081 +/- 170 mU, P = .008; oxytocin time-dinoprostone 798 +/- 11
      minutes, misoprostol 531 +/- 11 minutes, P = .009; dose intensity-dinoprostone
      11.3 +/- 0.1 mU/min, misoprostol 7.4 +/- 0.2 mU/min, P = .003. Misoprostol
      induced labor during the ripening period in 19 of 41 of patients, compared with 6
      of 42 after dinoprostone (P = .002). There was no difference in cesarean delivery
      (dinoprostone, 8/42; misoprostol, 9/42; P = 1.00). There was no difference in
      short-term neonatal outcome. No patient had hyperstimulation or required cesarean
      delivery for nonreassuring fetal assessment during the ripening period.
      CONCLUSION: A single dose of misoprostol administered in the outpatient setting
      significantly decreases oxytocin use, largely due to labor within the ripening
      period.

PMID- 15738011
TI  - Acute myocardial infarction in pregnancy and the puerperium: a population-based
      study.
AB  - OBJECTIVE: To estimate the population-based incidence and pregnancy outcomes of
      acute myocardial infarction (MI) in pregnancy. METHODS: Maternal and newborn
      hospital discharge records were linked to birth/death certificates for the 10
      year period January 1, 1991, to December 30, 2000, for the majority (98%) of
      deliveries in California. This database was searched for the diagnosis of acute
      MI, demographic characteristics, and pregnancy outcomes. Patients were divided
      into 4 groups: antenatal diagnosis, intrapartum diagnosis, up to 6-week
      postpartum diagnosis, and those without the diagnosis of acute MI. All groups
      were compared by Student t test or chi(2) or both, where appropriate. RESULTS: A
      total of 151 women had an acute MI during the antepartum (38%), intrapartum
      (21%), or 6-week postpartum (41%) period, giving an incidence rate of 1 in 35,700
      deliveries. The incidence rate increased over the study period. The maternal
      mortality rate was 7.3%, and maternal death only occurred in women with an acute
      MI before or at delivery (P < .01). Compared with women who did not have an acute
      MI, those with one were more likely to be older (30% were older than 35 years
      compared with 10%), multiparous (78% compared with 61%), non-Hispanic white (40%
      compared with 35%) or African Americans (15% compared with 7%). All measures of
      maternal and neonatal morbidity were increased in the acute MI group compared
      with those without an acute MI. Multivariate analysis identified chronic
      hypertension, diabetes, advancing maternal age, eclampsia, and severe
      preeclampsia as independent risk factors for acute MI. CONCLUSION: Acute MI
      during pregnancy remains a rare event, with significant maternal, fetal, and
      neonatal morbidity and mortality and maternal mortality limited to the antepartum
      and intrapartum period.

PMID- 15738012
TI  - Micturition syncope during pregnancy.
AB  - BACKGROUND: Micturition syncope is a relatively uncommon cause of sudden and
      temporary loss of consciousness. Most prevalent in older males, this condition is
      extremely rare in women. CASES: Two pregnant women presented with recurrent
      syncope. The syncopal events were more common in the early morning and were
      precipitated by the presence of a distended bladder, urinary urgency, assuming a
      standing position after either being supine or sitting, or associated with travel
      motion. Extensive neurology and cardiology evaluations were negative, and the
      events were considered consistent with micturition syncope. Both patients
      responded favorably to conservative voiding behavior modification measures
      throughout the remainder of pregnancy. CONCLUSION: Micturition syncope during
      pregnancy may not be a rare occurrence. This potentially dangerous condition is
      amenable to voiding behavior modification measures.

PMID- 15738013
TI  - Surgical staging for patients presenting with grade 1 endometrial carcinoma.
AB  - OBJECTIVE: To examine the impact of surgical staging of patients presenting with
      grade 1 endometrial cancer. METHODS: The charts of all patients who presented for
      surgery for endometrial cancer between March 1997 and July 2003 were analyzed for
      demographic data, final tumor histology, grade, stage, and complications.
      RESULTS: A total of 349 patients underwent surgical management for endometrial
      cancer. Preoperatively, 181 (52%) were identified with grade 1 disease, with a
      mean age of 61 years (range 27-89). Surgical staging (pelvic +/- para-aortic
      lymphadenectomy) was performed in 82% of cases and was omitted only in cases when
      disease was apparently confined to the endometrium and surgical risk was high. In
      staged patients, 3.2% had severe surgical complications. There were 2
      perioperative mortalities (1 pulmonary emboli and 1 myocardial infarct). In
      comparison of pre- and postoperative histology, 19% of patients were upgraded,
      with 15% grade 2, 0.5% grade 3, 2.5% serous or clear cell, and 1% mixed
      mesodermal tumor. Lymph node metastases were found in 3.9% of patients presenting
      with grade 1 endometrial cancer, and 10.5% had extrauterine spread (> IIb). High
      risk uterine features, including myometrial invasion more than 1/2, grade 3
      lesions, high-risk histologic variants, and/or cervical involvement, were found
      in 26% of the patients. No patients with stage Ia-IIb endometrioid cancer
      received adjuvant teletherapy or chemotherapy. Four patients with low-risk
      uterine features were found to have extrauterine disease. Twelve percent of
      patients received adjuvant therapy, and 17% avoided teletherapy and/or
      chemotherapy based on surgical staging. CONCLUSION: Surgical staging in patients
      presenting with grade 1 endometrial cancer significantly impacted postoperative
      treatment decisions in 29% of patients. Omitting lymphadenectomy in patients
      presenting with grade 1 endometrial cancer may lead to inappropriate
      postoperative management.

PMID- 15738014
TI  - Dysplasia associated with atypical glandular cells on cervical cytology.
AB  - OBJECTIVES: To estimate the rates of and identify risk factors for disease in
      women with atypical glandular cells of undetermined significance (AGUS). METHODS:
      From 1998-2001, 477 Pap tests at Hartford Hospital were classified as AGUS and
      met the inclusion criteria of this study. Findings were evaluated for 2 years
      from the initial test. Disease was defined as histology results with a finding of
      high-grade squamous intraepithelial lesion or greater. RESULTS: Disease was
      diagnosed in 9% of the women, including malignancy in 3%. Women with malignant
      appearing AGUS Pap tests had a higher rate of disease (29%) than women with
      benign-appearing (5%, P < .01) and unspecified AGUS Pap tests (13%, P < .03).
      Malignancies were associated with all subclassifications of AGUS Pap tests. Women
      aged less than 35 years were more likely to have disease than women aged 35 years
      or older (P < .02). Most women aged younger than 35 years had a squamous
      abnormality, whereas women aged 35 years or older had a greater diversity of
      squamous and glandular lesions and accounted for all cases of endometrial cancer,
      adenocarcinoma in situ, and cervical adenocarcinoma. Women with persistent AGUS
      Pap tests had a 31% rate of disease. The rate of disease among women with AGUS
      Pap tests collected by liquid-based cytology was 11%, compared with 6% among
      samples collected by the conventional method. CONCLUSION: These data suggest that
      women with atypical glandular cells are at substantial risk for dysplasia and
      malignancy. The rate of disease varies with the method of Pap test collection,
      age, presence of persistent AGUS Pap tests, and AGUS subclassification.

PMID- 15738015
TI  - Lack of adherence to practice guidelines for women with atypical glandular cells
      on cervical cytology.
AB  - OBJECTIVE: We sought to estimate the rates and types of evaluation in women with
      atypical glandular cells of undetermined significance (AGC-US) on cervical
      cytology and to assess these findings on the basis of published management
      guidelines. METHODS: The rates of histologic sampling, comprehensive initial
      evaluations, and secondary evaluations were assessed in 477 women with an AGC-US
      Pap test from 1998 to 2001. A comprehensive evaluation was defined as a
      colposcopy and an endocervical curettage with or without a cervical biopsy. For
      women aged 35 or older, a comprehensive evaluation also included an endometrial
      biopsy. A secondary evaluation consisted of a diagnostic cone biopsy. RESULTS:
      Sixty-four percent of women with an AGC-US Pap test had histologic sampling; 36%
      were followed by repeat Pap test only. Thirty-six percent of women with an AGC-US
      Pap test had a comprehensive evaluation. Women with an AGC-US Pap test that was
      subclassified as malignant-appearing had higher rates of histologic and
      comprehensive evaluations than women with a benign-appearing or unspecified AGC
      US Pap test (P < .01). Twenty-eight percent of women aged 35 or older had
      comprehensive evaluations compared with 57% of women younger than the age of 35
      (P < .01). Secondary evaluations were performed in 8% of women with persistent
      AGC-US Pap tests and 2% of women with malignant-appearing AGC-US Pap tests after
      negative initial histologic evaluations. Twelve of the 42 cases of disease (29%)
      were diagnosed more than 1 year from the initial AGC-US Pap test. CONCLUSION: On
      the basis of accepted management guidelines, these data suggest that women with
      AGC-US Pap tests are undermanaged in both their initial and secondary
      evaluations.

PMID- 15738016
TI  - Ovarian malignancy in breast cancer patients with an adnexal mass.
AB  - OBJECTIVE: The objectives of this study were to estimate ovarian malignancy rate
      in breast cancer patients with an adnexal mass and to identify variables
      predictive of malignancy. METHODS: This was a review from 1990-2002 including
      women with breast cancer diagnosed with an adnexal mass who subsequently
      underwent oophorectomy. Ovarian pathology was classified as benign, primary
      malignancy, or metastatic breast cancer. Women with preoperative evidence of
      malignancy were excluded. RESULTS: Of 129 cases reviewed, benign ovarian cysts
      were found in 113 cases (88%) and malignant ovarian neoplasms were found in 16
      cases (12%). Univariate logistic regression analyses were performed to determine
      predictors of malignancy. Complex masses were 29 times more likely to be
      malignant (P < .001). Women with estrogen-receptor-negative breast cancer had an
      increased risk for malignant adnexal masses (44%; OR 12.4, 95% confidence
      interval 2.4-65.1; P = .003). Patients with an elevated CA 125 had a 6.3-fold
      increased risk of malignancy, P = .02. Adnexal mass size greater than 5 cm also
      increased the risk of malignancy (18.8%; OR 4.6, 95% confidence interval 1.2
      17.3; P = .02). Malignant adnexal masses had a greater likelihood of being
      primary ovarian cancer than metastatic breast cancer by 7:1. CONCLUSION: An
      isolated adnexal mass in the breast cancer patient is most commonly a benign
      ovarian cyst. Adnexal masses associated with an increased CA 125, complex
      architecture by ultrasonography, or size greater than 5 cm are significant
      predictors of malignancy and are indications for referral to a gynecologic
      oncologist.

PMID- 15738017
TI  - Novel modification of the vertical rectus abdominis myocutaneous flap for
      neovagina creation.
AB  - OBJECTIVE: We describe a modification of the traditional vertical rectus
      abdominis myocutaneous flap for neovagina creation and our experience to date.
      METHODS: Our modified vertical rectus abdominis myocutaneous flap uses a smaller
      flap size with a full-thickness skin graft posteriorly to decrease the size of
      the abdominal wall defect. We have used the modified vertical rectus abdominis
      myocutaneous flap in 18 patients between March 1998 and March 2004 to create a
      neovagina after exenterative surgery. RESULTS: The mean age of the patients was
      54 years, and the mean body mass index was 27 (range 18-44). Twelve patients
      underwent a total pelvic, 5 anterior, and 1 posterior exenteration. Among the 13
      patients requiring a colostomy, the vertical rectus abdominis myocutaneous flap
      was taken from the contralateral side. In these patients, the urostomy was
      brought out on the vertical rectus abdominis myocutaneous flap donor side. There
      has been only 1 partial flap loss, which eventually resulted in a fully
      epithelialized neovagina. Eight patients at last follow-up were sexually active.
      Two other patients have died from recurrent disease, and 2 are alive with
      recurrence. The other 6 patients have no evidence of recurrent disease and,
      although not sexually active at the time of this report, have a viable and
      adequate neovagina. All patients had a successful primary closure of the
      abdominal wound in a vertical fashion. Three patients had superficial abdominal
      wound breakdown, which healed by secondary intention. CONCLUSION: The modified
      vertical rectus abdominis myocutaneous flap allows for creation of an adequate
      neovagina with a smaller abdominal wall defect.

PMID- 15738018
TI  - The effect of prematurity on vaginal birth after cesarean delivery: success and
      maternal morbidity.
AB  - OBJECTIVE: We sought to compare vaginal birth after cesarean (VBAC) success and
      uterine rupture rates between preterm and term gestations in women with a history
      of one prior cesarean delivery. Our hypothesis was that preterm women undergoing
      VBAC were more likely to be successful and have a lower rate of complications
      than term women undergoing VBAC. METHODS: We reviewed medical records of women
      with a history of a cesarean delivery who either attempted a VBAC or underwent a
      repeat cesarean delivery from 1995 through 2000 in 17 community and university
      hospitals. We collected information on demographics, medical and obstetric
      history, complications, and outcome of the index pregnancy. The primary analysis
      was limited to women with singleton gestations and one prior cesarean delivery.
      Statistical analysis consisted of bivariate and multivariable techniques.
      RESULTS: Among the 20,156 patients with one prior cesarean delivery, 12,463 (61%)
      attempted a VBAC. Mean gestational ages for the term and preterm women were 39.2
      weeks and 33.9 weeks of gestation, respectively. The VBAC success rates for the
      term and preterm groups were 74% and 82%, respectively (P < .001). Multivariable
      analysis showed that the VBAC success was higher (adjusted odds ratio 1.54, 95%
      confidence interval 1.27-1.86) in preterm gestations. A decreased risk of rupture
      among preterm gestations was suggested in these results (adjusted odds ratio
      0.28, 95% confidence interval 0.07-1.17; P = .08). CONCLUSION: Preterm patients
      undergoing a VBAC have higher success rates when compared with term patients
      undergoing a VBAC. Preterm patients undergoing VBAC may have lower uterine
      rupture rates.

PMID- 15738019
TI  - The impact of vaginal delivery in premature infants weighing less than 1,251
      grams.
AB  - OBJECTIVE: To evaluate whether mode of delivery is a predictor of poor short-term
      outcome at different birth weight categories in very low birth weight infants.
      METHODS: This study examined a cohort of infants weighing less than 1,251 g born
      at 2 perinatal centers from January 1, 2000, to December 31, 2003. Outborn
      infants or those with major anomalies were excluded from the study. Outcome
      variables included death, severe intraventricular hemorrhage, periventricular
      leukomalacia (PVL), and combined poor short-term outcomes (death, severe
      intraventricular hemorrhage, and PVL). RESULTS: Of the 397 infants who met
      enrollment criteria, 44% were born vaginally and 56% by cesarean delivery. The
      proportion of multiparous, breech presentation and prolonged rupture of membranes
      was significantly different between groups. For infants weighing less than 751 g,
      the risks of severe intraventricular hemorrhage (41% versus 22%; odds ratio [OR]
      2.79, 95% confidence interval [CI] 1.08-7.72) and combined poor short-term
      outcome (67% versus 41%; OR 2.95, 95% CI 1.25-6.95) were significantly higher if
      delivered vaginally. Among survivors weighing less than 751 g, the risk of severe
      intraventricular hemorrhage was higher among those delivered vaginally (24%
      versus 9%; OR 8.18, 95% CI 1.58-42.20). In infants less 1,251 g who survived,
      vaginal delivery had a strong association with PVL (5% versus 1%; OR 11.53, 95%
      CI 1.66-125). CONCLUSION: In infants less than 1,251 g who survived to discharge,
      vaginal delivery is associated with higher risk for PVL. Furthermore, in infants
      less than 751 g, vaginal delivery is a predictor for severe intraventricular
      hemorrhage and combined poor short-term outcome. The negative impact of vaginal
      delivery mode decreases as birth weight category increases.

PMID- 15738020
TI  - Prediction of preterm delivery in the second trimester.
AB  - OBJECTIVE: The aim of this study was to estimate the probability of spontaneous
      delivery at 34 weeks or less according to cervical assessment by transvaginal
      scan associated with previous obstetric history. METHODS: Ultrasound transvaginal
      cervical length and presence of funneling were evaluated in 1,958 singleton
      pregnancies between 21 and 24 weeks of gestation. For the prediction of preterm
      delivery, the results of cervical assessment were analyzed in association with
      the previous obstetric history of preterm delivery, spontaneous miscarriage, and
      curettage. Sensitivity, specificity, and positive and negative predictive values
      for the various cutoff cervical lengths in the groups with or without previous
      history of preterm delivery were calculated. Multivariable regression analysis
      was used to identify the predictive factors for preterm delivery at 34 weeks or
      less. RESULTS: The incidence of spontaneous delivery at gestational age of 34
      weeks or less was 3.4%. The mean cervical length was 30.1 mm (standard deviation
      10.1 mm) in the group with previous history of prematurity (n = 180) and 35.8 mm
      (standard deviation 7.9 mm) in the group without previous history of prematurity
      (P < .001). The mean cervical length in the group of patients who delivered at or
      before 34 weeks was 23.8 mm, and for patients who delivered after 34 weeks it was
      35.6 mm (P < .001). The mean gestational age at delivery was significantly lower
      in the group with funneling compared with the group without funneling (33.5 weeks
      versus 38.8 weeks, P < .001). Logistic regression analysis demonstrated that
      cervical length, funneling, and history of previous preterm delivery were
      independent contributors for preterm delivery. CONCLUSION: Ultrasound cervical
      assessment may be useful in the prediction of preterm delivery, but it should
      also be considered in association with the obstetric history of prematurity.

PMID- 15738021
TI  - Obesity-related complications in Danish single cephalic term pregnancies.
AB  - OBJECTIVE: Our objective was to investigate the relationship between prepregnancy
      and obstetric body mass index (BMI) as well as fetal complications in a large,
      unselected cohort of Danish women with single cephalic pregnancies. METHODS: A
      cohort of 8,092 women from the Copenhagen First Trimester Study with a registered
      prepregnancy BMI and a single cephalic term delivery were stratified into 3 BMI
      groups: normal weight (BMI < 25 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and
      obese (BMI >/= 30 kg/m(2)). The effects of BMI and parity on the outcome were
      analyzed using multivariate logistic regression analyses. RESULTS: Overweight
      women had an odds ratio (OR) of 3.4 for diabetes, 1.9 for hypertension, 1.7 for
      preeclampsia, and 1.5 for cesarean delivery. The corresponding figures for obese
      women were 15.3, 4.8, 2.7, and 1.7, respectively. No relationship was found
      between BMI and vacuum extraction. Obese women had an increased risk of
      delivering macrosomic but also low birth weight children. No differences existed
      among the 3 weight groups with regard to neonatal morbidity estimated by Apgar
      score, umbilical cord pH, or admittance to a neonatal intensive care unit.
      Nulliparous women had an increased incidence of preeclampsia (OR 2.8),
      hypertension (OR 1.9), emergency cesarean delivery (OR 3.4), vacuum extraction
      (OR 5.6), and perineal rupture (OR 1.7) but a lower frequency of elective
      cesarean delivery (OR 0.25). CONCLUSION: The rate of complications during
      pregnancy and delivery increases with an increasing prepregnancy BMI in women
      with single cephalic term pregnancies, particularly in nulliparous women.

PMID- 15738022
TI  - Term-gestation low birth weight and health-compromising behaviors during
      pregnancy.
AB  - OBJECTIVE: To estimate the association between term-gestation low birth weight
      (term-LBW) rates and increasing numbers of health-compromising behaviors during
      pregnancy. METHODS: Retrospective cohort study of 78,397 term live births in
      Kansas City, Missouri, 1990-2002. Information on maternal and newborn
      characteristics was obtained form birth certificate records. Health-compromising
      behavior, specifically, smoking, alcohol, and drug use, was classified by the
      numbers and combinations of behaviors engaged in during pregnancy. Covariates
      included race, age, interconception interval, education, Medicaid status, medical
      risk factors, adequacy of prenatal care, and marital status. RESULTS: The cohort
      was 61% white, 16% less than 20 years of age, 45% on Medicaid, 24% with medical
      risk factor, and 45% single pregnant women. Overall term-LBW rate was 3.3%, and
      it increased with numbers of health-compromising behaviors: 2.6% (none), 5.5%
      (1), 10.8% (2), and 18.5% (3), P < .001. Unadjusted odds ratio (OR) for term-LBW
      increased with increasing numbers of behaviors (OR 1.0 [none]; 2.3, 95%
      confidence interval 2.0-2.4 [smoking]; 0.9, 0.6-1.4 [alcohol]; 2.1, 1.5-3.0
      [drugs]; 4.6, 3.6-5.8 [smoking + alcohol]; 4.4, 3.6-5.4 [smoking + drugs]; 4.2,
      1.5-11.9 [drugs + alcohol]; 8.4, 6.2-11.5 [smoking + alcohol + drugs]). However,
      on adjusting for covariates, smoking, alone (OR 2.3, 2.0-2.5) or in combinations
      with other behaviors (OR 4.4, 3.4-5.7 [smoking + alcohol]; 2.0, 1.6-2.6 [smoking
      + drugs]; and 3.3, 2.2-4.7 [smoking + alcohol + drugs]) remained the major risk
      factor for term-LBW. CONCLUSION: Smoking alone or in combination with alcohol
      and/or drug use is associated with term-LBW among women who engage in health
      compromising behaviors. The effect is especially pronounced when smoking is
      combined with alcohol consumption.

PMID- 15738023
TI  - Evaluation of clinical methods for diagnosing bacterial vaginosis.
AB  - OBJECTIVE: To determine whether the current clinical criteria for diagnosing
      bacterial vaginosis can be simplified by using 2 clinical criteria rather than
      the standard 3 of 4 criteria (Amsel's criteria). METHODS: This was a prospective
      observational study of 269 women undergoing a vaginal examination in the Women's
      Primary Care Center, Division of Research, or Colposcopy Clinic at Women &
      Infants Hospital. All 4 clinical criteria for diagnosing bacterial vaginosis were
      collected, and Gram stain was used as the gold standard. Sensitivity and
      specificity were calculated for each individual criterion, combinations of
      criteria, and a colorimetric pH and amine card. Receiver operating characteristic
      curve was generated to estimate the preferred pH and percentage of clue cells for
      diagnosing bacterial vaginosis. RESULTS: The prevalence of bacterial vaginosis in
      our study population was 38.7%. Vaginal pH was the most sensitive of all the
      criteria, at 89%, and a positive amine odor was the individual criteria with the
      highest specificity, at 93%. Similar specificity was seen with combinations of 2
      criteria and Amsel's criteria. Receiver operating characteristic curve analysis
      yielded a preferred pH and percentage of clue cells of 5.0 and 20%, respectively.
      However, a pH of 4.5 or greater improves sensitivity with minimal loss of
      specificity. CONCLUSION: The clinical criteria for diagnosing bacterial vaginosis
      can be simplified to 2 clinical criteria without loss of sensitivity and
      specificity.

PMID- 15738024
TI  - Spontaneous resolution of asymptomatic Chlamydia trachomatis in pregnancy.
AB  - OBJECTIVE: We sought to estimate the rate of spontaneous resolution of
      asymptomatic Chlamydia trachomatis in pregnancy and to evaluate factors
      associated with its resolution. METHODS: A cohort of women enrolled in a large
      multicenter randomized bacterial vaginosis antibiotic trial (metronidazole versus
      placebo) that, when randomly allocated, had asymptomatic C trachomatis diagnosed
      by urine ligase chain reaction (from frozen archival specimens) between 16(0/7)
      and 23(6/7) weeks were included. The urine ligase chain reaction is a highly
      accurate predictor of genital tract chlamydial infection. A follow-up ligase
      chain reaction was performed between 24(0/7) and 29(6/7) weeks. RESULTS: A total
      of 1,953 women were enrolled in the original antibiotic trial; 1,547 (79%) had
      ligase chain reaction performed both at randomization and follow-up. Women
      receiving antibiotics effective against Chlamydia between randomization and
      follow-up or having symptomatic Chlamydia infection were excluded (26 women). Of
      the 140 women (9%) who were diagnosed as positive via the initial ligase chain
      reaction assay, 61 (44%) had spontaneous resolution of Chlamydia by the follow-up
      ligase chain reaction assay. Factors associated with spontaneous resolution
      included older age (P = .02), more than 5 weeks from randomization to follow-up
      (P = .02), and a greater number of lifetime sexual partners (P = .02). Using a
      logistic regression model, maternal age and a greater-than-5-week follow-up
      interval remained significant; for every 5-year increase in maternal age, the
      odds of a positive result on the ligase chain reaction test at follow-up
      decreased by 40% (odds ratio 0.6; 95% confidence interval 0.4-0.9). Race,
      substance abuse, parity, and treatment with metronidazole were not associated
      with spontaneous resolution. Gram stain score and vaginal pH at randomization and
      follow-up also were not associated. CONCLUSION: The prevalence of asymptomatic C
      trachomatis in pregnancy was 9%; infection resolved spontaneously in almost half
      of these women. The association of older age and increasing time interval to
      spontaneous resolution of Chlamydia is consistent with a host immune-response
      mechanism.

PMID- 15738025
TI  - Age-specific incidence rates for self-reported uterine leiomyomata in the Black
      Women's Health Study.
AB  - OBJECTIVE: Uterine leiomyomata represent a major public health problem for black
      women in the United States, but limited data are available on age-incidence
      curves in this high-risk population. We estimated overall and age-specific
      incidence rates for self-reported uterine leiomyomata in a large cohort of
      African-American women in the United States. METHODS: Data were derived from the
      Black Women's Health Study, an ongoing prospective cohort study of 59,000 black
      women from across the United States who were aged 21-69 years at baseline (ie,
      1995). From March 1997 through March 2001, we followed up 22,895 premenopausal
      women with no prior diagnosis of uterine leiomyoma. Poisson regression was used
      to estimate overall and age-specific incidence rates and 95% confidence intervals
      (CIs) for self-reported uterine leiomyoma. In a subset of 248 patients who were
      selected randomly from the total case group, the self-reported diagnosis was
      verified in 96% of cases who released their medical records. RESULTS: During
      76,711 woman-years of follow-up, 2,637 incident cases of uterine leiomyomata
      reported as confirmed by pelvic examination (n = 358), ultrasonography (n =
      2,006), or hysterectomy (n = 273) were observed. Incidence rates per 1,000 woman
      years were 34.4 (95% CI 33.1-35.7) for all cases combined, 29.7 (95% CI 28.5
      30.9) for cases confirmed by ultrasonography or hysterectomy, and 3.6 (95% CI 3.2
      4.0) for cases confirmed by hysterectomy. The incidence rate peaked at ages 40-44
      years for all cases combined (incidence rate 45.6, 95% CI 42.0-49.5) and for
      cases confirmed by ultrasonography or hysterectomy (incidence rate 39.8, 95% CI
      36.5-43.4), and peaked at ages 45-49 years for cases confirmed by hysterectomy
      (incidence rate 8.3, 95% CI 6.4-10.7). CONCLUSION: Overall incidence rates for
      self-reported uterine leiomyomata were consistent with other U.S studies in black
      women and confirmed a high burden of disease in this population. Age-specific
      incidence rates showed a later peak incidence than that observed among U.S. black
      women in previous studies.

PMID- 15738026
TI  - Gynecologic cancer as a "sentinel cancer" for women with hereditary nonpolyposis
      colorectal cancer syndrome.
AB  - OBJECTIVE: Women with hereditary nonpolyposis colorectal cancer syndrome have a
      40-60% lifetime risk for colon cancer, a 40-60% lifetime risk for endometrial
      cancer, and a 12% lifetime risk for ovarian cancer. A number of women with
      hereditary nonpolyposis colorectal cancer syndrome will have more than one cancer
      in their lifetime. The purpose of this study was to estimate whether women with
      hereditary nonpolyposis colorectal cancer syndrome who develop 2 primary cancers
      present with gynecologic or colon cancer as their "sentinel cancer." METHODS:
      Women whose families fulfilled Amsterdam criteria for hereditary nonpolyposis
      colorectal cancer syndrome and who developed 2 primary colorectal/gynecologic
      cancers in their lifetime were identified from 5 large hereditary nonpolyposis
      colorectal cancer syndrome registries. Information on age at cancer diagnoses and
      which cancer (colon cancer or endometrial cancer/ovarian cancer) developed first
      was obtained. RESULTS: A total of 117 women with dual primary cancers from 223
      Amsterdam families were identified. In 16 women, colon cancer and endometrial
      cancer/ovarian cancer were diagnosed simultaneously. Of the remaining 101 women,
      52 (51%) women had an endometrial or ovarian cancer diagnosed first. Forty-nine
      (49%) women had a colon cancer diagnosed first. For women who developed
      endometrial cancer/ovarian cancer first, mean age at diagnosis of endometrial
      cancer/ovarian cancer was 44. For women who developed colon cancer first, the
      mean age at diagnosis of colon cancer was 40. CONCLUSION: In this large series of
      women with hereditary nonpolyposis colorectal cancer syndrome who developed 2
      primary colorectal/gynecologic cancers, endometrial cancer/ovarian cancer was the
      "sentinel cancer," preceding the development of colon cancer, in half of the
      cases. Therefore, gynecologists and gynecologic oncologists play a pivotal role
      in the identification of women with hereditary nonpolyposis colorectal cancer
      syndrome.

PMID- 15738028
TI  - Antibiotic prophylaxis and non-group B streptococcal neonatal sepsis.
AB  - OBJECTIVE: To assess the effect of increased use of intravenous penicillin for
      group B streptococcus (Streptococcus agalactiae, GBS) antibiotic prophylaxis on
      non-GBS neonatal sepsis and antibiotic resistance. METHODS: We undertook a
      nonconcurrent cohort study. Microbiology cultures originating from infants with
      early-onset neonatal sepsis in our neonatal intensive care unit (NICU) from 1992
      to 1999 were reviewed. Prevalence of non-GBS neonatal sepsis in the control
      period (January 1, 1992, through June 30, 1995) was compared with that in the
      study period (October 1, 1995, through August 31, 1999), when the protocol
      changed. Chi-squared or Fisher exact tests were used to determine statistical
      significance. Resistance patterns were compared in similar fashion. RESULTS: The
      prevalence of non-GBS neonatal sepsis was 1.2 per 1,000 (36 of 31,133) live
      births before and 1.1 per 1,000 (32 of 28,733) live births after institution of
      the Centers for Disease Control and Prevention culture-based protocol (P = .97).
      Our power analysis assumed a doubling in the rate of non-GBS sepsis and required
      21,220 live births per arm. Gram-negative and gram-positive sepsis prevalences
      were not significantly different. Escherichia coli and GBS resistance patterns
      did not change. CONCLUSION: Institution of a protocol for GBS antibiotic
      prophylaxis significantly decreased the rate of GBS neonatal sepsis but did not
      increase the rate of non-GBS neonatal sepsis. Antibiotic resistance patterns of
      these organisms were not affected.

PMID- 15738027
TI  - Risk factors for young premenopausal women with endometrial cancer.
AB  - OBJECTIVE: Endometrial cancer is the most common gynecologic malignancy in the
      United States. The mean age at diagnosis is 61 years; however, 5-30% of women are
      aged younger than 50 years at the time of diagnosis. The objective of this study
      was to conduct a clinical and pathologic review of endometrial cancers diagnosed
      in premenopausal women aged younger than 50 years, to better identify the risk
      factors for this subgroup of women. METHODS: We conducted a retrospective cohort
      study of patients with histologically confirmed endometrial cancer treated at the
      University of Texas, M. D. Anderson Cancer Center from 1989 to 2003. Clinical
      characteristics including age, body mass index (BMI), parity, diabetes, and
      personal or family history of cancer were obtained from the medical record.
      Pathologic information was obtained from pathology reports. RESULTS: Twelve
      percent (188/1531) of all patients with endometrial adenocarcinoma were aged
      younger than 50 years. The mean age at diagnosis was 41 years (range 21-49
      years). Mean BMI was 34 kg/m(2) (range 18-68); 58% of patients had a BMI of 30 or
      greater. Fifty-five percent were nulliparous and 39% reported irregular menstrual
      cycles. The incidence of both diabetes and hypertension was 23%. Thirty-six
      patients (19%) had synchronous ovarian cancers. CONCLUSION: We found that the
      majority of patients diagnosed with endometrial cancer at a young age were obese
      and nulliparous. In addition, we found a high incidence of synchronous primary
      ovarian cancers in this cohort of young, premenopausal women.

PMID- 15738029
TI  - Late first-trimester placental disruption and subsequent gestational
      hypertension/preeclampsia.
AB  - OBJECTIVE: To evaluate the potential relationship between placental disruption in
      weeks 13 and 14 and the subsequent development of gestational hypertension or
      preeclampsia. METHODS: Using subjects recruited during a randomized trial funded
      by the National Institute of Child Health and Human Development, which compared
      early amniocentesis and late transabdominal chorionic villus sampling (CVS) in
      weeks 13 and 14, rates of gestational hypertension and preeclampsia were compared
      between cases with varying degrees of placental disruption. RESULTS: A total of
      3,698 of 3,775 randomized subjects had cytogenetically normal pregnancies and
      were analyzed. A significantly higher rate of hypertension/preeclampsia was
      observed in the late CVS group (5.4%, n = 1,878) compared with the early
      amniocentesis cohort (3.5%, n = 1,820; P = .005). This difference persisted after
      controlling for maternal age, body mass index, parity, previous preterm delivery,
      smoking, and fetal gender. Early amniocentesis cases were further stratified on
      the basis of whether the placenta had been penetrated (n = 460) or not (n =
      1,360). Risk of hypertensive complications was lowest if the placenta was not
      traversed (3.4%), greater with placental penetration (3.9%), and highest when the
      placenta was directly sampled during CVS (5.4%, P = .02). CONCLUSION: We
      hypothesize that focal disruption of the placenta at 13-14 weeks may increase the
      risk of hypertension/preeclampsia. These findings provide support for the theory
      that disturbances in early placentation lead subsequently to maternal
      hypertension.

PMID- 15738030
TI  - Relationship of maternal body mass index and height to twinning.
AB  - OBJECTIVE: Increasing use of fertility drugs is considered the primary cause for
      the recent increase in dizygotic twinning in developed countries. However,
      dizygotic twinning has also been related to obesity in foreign populations. We
      sought to confirm this relationship in U.S. pregnancies, which predated
      widespread use of fertility drugs. METHODS: We analyzed 51,783 pregnancies (561
      twin) in the Collaborative Perinatal Project, which took place at 12 hospitals in
      the United States from 1959 to 1966. The occurrence of twinning was compared
      according to maternal self-reported prepregnant body mass index (BMI) of less
      than 20, 20-24.99, 25-29.99, and 30 kg/m(2) or greater, before and after
      adjustment for confounding factors. RESULTS: There was a statistically
      significant trend for increased risk of total twinning with increasing BMI (P <
      .001). The odds of monozygous twinning were not significantly related to BMI, but
      the odds of dizygous twinning were significantly related to increased BMI. After
      adjusting for maternal race, age, parity, and height, the odds of dizygous
      twinning were still significantly elevated among women with a BMI of 30 or more,
      and the trend for increasing risk of dizygous twinning with increasing BMI was
      significant (P = .001). The trend for increased twinning with increasing height
      was also significant. Women in the tallest quartile of height had a significantly
      increased odds ratio for dizygous twin pregnancies, although not of the same
      magnitude as women with BMI over 30. CONCLUSION: We confirmed the association of
      maternal weight and height with dizygotic twinning in a U.S. population among
      which fertility drugs were not a factor.

PMID- 15738031
TI  - Clinical case mix adjustment of cesarean delivery rates in U.S. military
      hospitals, 2002.
AB  - OBJECTIVE: To assess whether significant variations in observed cesarean rates in
      U.S. military hospitals may be attributed to differences in clinical case mix.
      METHODS: Hospital discharge records for births in U.S. military hospitals in 2002
      were grouped into mutually exclusive clinical strata to calculate predicted
      cesarean rates for subgroups defined by maternal race, health plan, hospital
      location, delivery volume, teaching status, and neonatal intensive care unit
      (NICU) status. The 95% confidence interval (CI) around each standardized ratio
      (SR) of the observed-to-predicted cesarean rate was used to assess statistical
      significance. RESULTS: Observed cesarean rates were significantly higher than
      predicted rates for small hospitals (23.1% and 20.4%, respectively, SR 1.13, 95%
      CI 1.08-1.19), teaching hospitals (23.7% and 22.5%, respectively, SR 1.05, 95% CI
      1.02-1.08), black women (25.1% and 22.8%, respectively, SR 1.10, 95% CI 1.05
      1.14), and other minorities (22.7%, and 21.6%, respectively, SR 1.05, 95% CI 1.01
      1.09). No significant differences between observed and predicted cesarean rates
      were found across hospital locations or NICU status. Significant differences
      found for non-managed care beneficiaries were attributed to teaching status of
      the hospitals in which they delivered. CONCLUSION: Clinical case mix does not
      adequately account for the relatively high rates of cesarean delivery observed
      for small hospitals and teaching hospitals and among black women in the study
      population. Further study is recommended to identify additional clinical and
      nonclinical factors that should be considered when comparing performance across
      institutions, health plans, or individual providers.

PMID- 15738032
TI  - Using an electronic medical record to improve communication within a prenatal
      care network.
AB  - OBJECTIVE: In 2002, the Institute of Medicine called for the introduction of
      information technologies in health care settings to improve quality of care. We
      conducted a review of hospital charts of women who delivered before and after the
      implementation of an intranet-based computerized prenatal record in an inner-city
      practice. Our objective was to assess whether the use of this record improved
      communication among the outpatient office, the ultrasonography unit, and the
      labor floor. METHODS: The charts of patients who delivered in August 2002 and
      August 2003 and received their prenatal care at the Comprehensive Family Care
      Center at Montefiore Medical Center were analyzed. Data collected included the
      presence of a copy of the prenatal record in the hospital chart, the date of the
      last documented prenatal visit, and documentation of any prenatal ultrasonograms
      performed. RESULTS: Forty-three charts in each group were available for review.
      The prenatal chart was absent in 16% of the charts of patients from August 2002
      compared with only 2% in August 2003 charts (P < .05). Among charts with prenatal
      records available, the median length of time between the last documented prenatal
      visit and delivery was significantly longer for August 2002 patients compared
      with August 2003 patients (36 compared with 4 days, respectively, P < .001). All
      patients received prenatal ultrasonograms, but documentation of the ultrasonogram
      was missing from 16% of the August 2002 charts compared with none of the August
      2003 charts (P = .01). CONCLUSION: The use of a paperless, hospital intranet
      based prenatal chart significantly improves communication among providers.

PMID- 15738033
TI  - Prognostic value of umbilical artery Doppler studies in unselected preterm
      deliveries.
AB  - OBJECTIVE: To evaluate the prognostic value of umbilical artery Doppler studies
      in premature deliveries. METHODS: In this cohort study of 582 singleton
      pregnancies delivered between 24 and 35 weeks of gestation, we evaluated the
      ratio of peak-systolic to end-diastolic (S/D) blood flow velocities in the
      umbilical artery of all the patients. The correlations among the results of the
      Doppler studies, short-term neonatal complications, and the infants'
      neurodevelopmental outcome at 2 years were studied by univariable and
      multivariable methods. RESULTS: The prevalences of either neonatal death or
      cerebral palsy among the 266 (45.7%) growth restricted fetuses were 3.4% (3/88)
      in pregnancies with a S/D ratio below the 95th percentile, 4.9% (5/103) in
      pregnancies with a S/D at or above the 95th percentile, and 17.3% (13/75) in
      those with absent or reversed end-diastolic blood flow in the umbilical artery (P
      for trend = .001). The corresponding figures in the 316 pregnancies with adequate
      fetal growth were 6.4% (15/234) and 4.3% (3/69) among pregnancies with a S/D
      ratio below and at or above 95th percentile, respectively, whereas no cases of
      either neonatal death or cerebral palsy were recorded in the 13 pregnancies with
      adequate fetal growth and absent or reversed end-diastolic blood flow velocity (P
      for trend = .28; chi(2) for heterogeneity of linear trends compared with growth
      restricted infants = 7.02, P = .008). In logistic regression, in pregnancies
      complicated by fetal growth restriction, absent or reversed end-diastolic blood
      flow in the umbilical artery was still associated with an increased risk of
      either neonatal death or cerebral palsy even after adjustment for gestational age
      and proportion of expected birth weight, (odds ratio 3.2, 95% confidence interval
      1.18-8.66, P = .02). CONCLUSION: Absent or reversed end-diastolic flow in the
      umbilical artery is an independent predictor of either neonatal death or cerebral
      palsy in preterm growth-restricted fetuses. In the absence of fetal growth
      restriction, umbilical artery Doppler study was associated with none of the
      infant outcome parameters studied.

PMID- 15738034
TI  - The influence of pregnancy on arterial compliance.
AB  - OBJECTIVE: To examine the effect of pregnancy and the interval between
      pregnancies on arterial compliance as measured by mean arterial pressure (MAP)
      and pulse pressure. METHODS: We conducted a 3-month chart review of deliveries at
      a tertiary care hospital (index pregnancies). Data collected included
      demographics, obstetric history, blood pressures, prepregnancy weight, weight
      gain, and neonatal outcome. If a subject's first delivery occurred at our
      institution, these records were reviewed in a similar fashion. Mean antepartum
      MAP and pulse pressure were calculated and compared for each trimester between
      index and first pregnancies. Statistical methods employed included repeated
      measures analysis of variance, repeated measures analysis of covariance, and
      correlation analysis. RESULTS: Two hundred eighty-five charts were reviewed.
      Forty-seven women had complete data covering both index and first pregnancy. Mean
      arterial pressure was significantly higher in all trimesters of first compared
      with index pregnancies (first pregnancy-first trimester 82.0 +/- 8.1 mm Hg, index
      pregnancy-first trimester 79.4 +/- 7.6 mm Hg, P = .032; first-second trimester
      81.6 +/- 6.7 mm Hg, index-second trimester 78.7 +/- 6.6 mm Hg, P = .016; first
      third trimester 83.9 +/- 6.9 mm Hg, index-third trimester 81.6 +/- 6.9 mm Hg, P =
      .047). Repeated measures analysis of covariance confirmed that pregnancy order
      contributed independently to differences in MAP. The interval between pregnancies
      was found to be inversely related to the difference in MAP from first to index
      pregnancies by trimester (r = -0.41, P = .004) and the change in MAP within
      pregnancy from first to third trimester (r = -0.31, P = .046). CONCLUSION: Mean
      arterial pressure is reduced in subsequent pregnancies compared with first
      pregnancies. This raises the possibility that pregnancy plays a role in modifying
      cardiovascular compliance. Consistent with this, the effect has temporal
      limitations in that the shorter the interval between pregnancies, the greater the
      reduction in MAP.

PMID- 15738035
TI  - Abnormal endothelium-dependent microvascular reactivity in recently preeclamptic
      women.
AB  - OBJECTIVE: To assess endothelial function at the level of skin microvasculature,
      using iontophoretic administration of acetylcholine (endothelium-dependent
      vasodilator) and sodium nitroprusside (endothelium-independent vasodilator), in
      women who recently had a preeclamptic pregnancy. METHODS: Microvascular skin
      reactivity was assessed by laser Doppler perfusion monitoring and iontophoresis
      of acetylcholine (ACh) and sodium nitroprusside (SNP) in 25 women with a history
      of early onset preeclampsia and 23 women with previous uncomplicated pregnancies,
      all of whom were between 3 and 11 months postpartum. RESULTS: Mean (+/- standard
      error of the mean) ACh-mediated vasodilatation, expressed as a percentage
      increase in flux, was higher in women who recently had a preeclampsia than in
      controls (535 +/- 46% versus 314 +/- 29%, P < .001). In contrast, SNP-mediated
      vasodilatation was not significantly different (560 +/- 71% versus 483 +/- 69%, P
      = .4) in both groups. Linear regression analysis revealed that the difference in
      ACh-mediated vasodilatation was explained by preeclampsia (P = .004), whereas
      vascular risk factors such as maternal age, diastolic blood pressure, and family
      history of premature cardiovascular diseases had no significant effect.
      CONCLUSION: The increased ACh-mediated vasodilatation in the microcirculation of
      recently preeclamptic women indicates abnormal endothelial function. Furthermore,
      it may represent a compensatory response to an impaired vasodilatory response of
      the macrocirculation, thereby supporting the hypothesis of an underlying
      (micro)angiopathy.

PMID- 15738036
TI  - Body mass index, provider advice, and target gestational weight gain.
AB  - OBJECTIVE: To study the relationships among prepregnancy body mass index (BMI),
      women's target gestational weight gain, and provider weight gain advice. METHODS:
      Project WISH, the acronym for Women and Infants Starting Healthy, is a
      longitudinal cohort study of pregnant women in the San Francisco Bay area. We
      excluded subjects with preterm birth, multiple gestation, or maternal diabetes.
      RESULTS: Among overweight women (prepregnancy BMI 26.1-29.0), 24.1% reported a
      target weight gain above the Institute of Medicine (IOM) guidelines, compared
      with 4.3% of normal weight women (P < .001). Among women with a low prepregnancy
      BMI (< 19.8), 51.2% reported a target weight gain below the guidelines, compared
      with 10.4% of normal weight women (P < .001). These patterns persisted in a
      multivariate analysis. Latina ethnicity, lower maternal education, low
      prepregnancy BMI (< 19.8), lack of provider advice about weight gain, and
      provider advice to gain below guidelines were all independently associated with a
      target weight gain below IOM guidelines. Prepregnancy BMI more than 26,
      multiparity, lower age, and provider advice to gain above guidelines were all
      associated with a target gain above IOM guidelines. CONCLUSION: Women's beliefs
      about the proper amount of weight gain and provider recommendations for weight
      gain vary significantly by maternal prepregnancy BMI. Many women report incorrect
      advice about gestational weight gain, and women with high or low prepregnancy BMI
      are more likely to have an incorrect target weight gain. New approaches to
      provider education are needed to implement the IOM guidelines for gestational
      weight gain.

PMID- 15738037
TI  - Posterior sacculation of the uterus in a patient presenting with flank pain at 29
      weeks of gestation.
AB  - BACKGROUND: Uterine sacculation is a rare complication of pregnancy and may cause
      substantial peripartal morbidity. CASE: A possible diagnosis of posterior uterine
      sacculation was raised when a 34-year-old Gravida 1 Para 1 presented with
      bilateral flank pain at 29 weeks. Sonographic and magnetic resonance imaging
      findings confirmed the diagnosis and demonstrated bilateral dilated renal
      pelvises. Bilateral nephrostomas were placed, offering the patient considerable
      relief. A healthy female newborn was delivered by cesarean at 34 1/7 weeks.
      Operative findings confirmed the posterior sacculation of the uterus. CONCLUSION:
      Early diagnosis of sacculation of the uterus is necessary to limit maternal and
      fetal morbidity and mortality. For a detailed evaluation of the pelvic anatomy,
      we recommend the use of magnetic resonance imaging in the third trimester.

PMID- 15738038
TI  - Herceptin (trastuzumab) therapy during pregnancy: association with reversible
      anhydramnios.
AB  - BACKGROUND: Herceptin (trastuzumab), a new a chemotherapeutic agent, is a
      monoclonal antibody that blocks the human epidermal growth factor receptor 2
      protein. There is no reported experience with use of this agent during pregnancy
      and possible effects on the fetus. CASE: A patient with breast cancer was treated
      with Herceptin during pregnancy. This treatment was associated with anhydramnios,
      which resolved slowly after the drug was discontinued. CONCLUSION: Although
      listed as a category B drug, experience with Herceptin in human pregnancy is
      limited, and it should be used with caution. Investigation of the role of human
      epidermal growth factor receptor 2 protein in the embryonic kidney may further
      our understanding of amniotic fluid dynamics.

PMID- 15738039
TI  - Use of follicle-stimulating hormone test to predict poor response in in vitro
      fertilization.
AB  - OBJECTIVE: Optimized ovarian stimulation protocols are required for the success
      of in vitro fertilization (IVF). The purpose of this study was to estimate
      whether the ovarian reserve test using exogenous follicle-stimulating hormone
      (FSH) could predict ovarian response in IVF. METHODS: This was a prospective
      observational study of 110 patients who underwent their first IVF cycle. The FSH
      test was administered as 150 IU of urinary FSH daily from day 3 to day 6 of the
      menstrual cycle preceding the IVF cycle for evaluation of the plasma estradiol
      level. Outcomes of IVF, including ovarian response, were analyzed. RESULTS: A
      negative correlation was observed between the duration of stimulation and the
      result of the FSH test (r = -.238, P = .014) and between the dose of FSH per
      retrieved mature oocyte (metaphase II oocyte) and the result of the FSH test (r =
      -.308, P < .001). In addition, our results showed that the result of the FSH test
      was significantly lower in poor responders defined by FSH of 400 IU/metaphase II
      oocyte or greater (207 +/- 149 compared with 293 +/- 174 pg/mL, P = .007).
      CONCLUSION: The FSH test can be a useful tool for determining the conditions of
      individualized clinical management plans and optimizing stimulation protocols in
      IVF.

PMID- 15738041
TI  - Urinary urgency and frequency: what should a clinician do?
AB  - Obstetrician-gynecologists often care for women with urinary symptoms of urgency
      and frequency. These symptoms are bothersome and treatable. Although it is rare
      that serious disease is causative, the clinician must be alert to ominous signs
      and physical findings. Most patients experience relief of their symptoms after a
      simple initial evaluation with appropriately directed treatment. A step-wise
      evaluation includes the directed history and physical, assessment of urinary
      habits, typically with a urinary diary, and occasionally an assessment of voiding
      efficiency, typically with a postvoid residual. Treatments may include myofascial
      therapy when trigger points are present on physical examination. Behavioral
      therapy and pharmaceuticals also play an important role. Persistent symptoms,
      hematuria, severe de novo postoperative symptoms, and ominous physical findings
      may warrant specialty consultation.

PMID- 15738040
TI  - Protein supplementation and the incidence of apoptosis and oxidative stress in
      mouse embryos.
AB  - OBJECTIVE: To estimate the effect of protein supplementation of culture media on
      reactive oxygen species production and incidence of apoptosis in preimplantation
      mouse embryos. METHODS: A total of 72 two-cell mouse embryos were cultured in
      human tubal fluid (HTF) alone (HTF-alone, control) and 71 embryos in HTF with
      protein supplementation (10% serum substitute supplement; HTF-SSS) for 72 hours.
      Total cell number per embryo was determined by staining with Hoechst 33258.
      Allocation of inner cell mass and trophectoderm in blastocysts and incidence of
      apoptosis were determined by confocal microscopy. Levels of reactive oxygen
      species in culture media were measured by chemiluminescence assay using luminol
      as probe. RESULTS: Blastocyst development, total cell number, and the inner cell
      mass/trophectoderm ratio were similar between the 2 groups. The blastocyst
      hatching rate was significantly higher in the HTF-SSS group than in the HTF-alone
      group (20% compared with 4%, P = .007). Level of reactive oxygen species was
      significantly higher in HTF-alone compared with HTF-SSS at 24 hours (median and
      interquartile range 28 [13, 43] compared with 0 [0, 1], P = .02), 48 hours (24
      [21, 26] compared with 2 [1, 2], P = .02), and 72 hours (26 [9, 32] compared with
      2 [2, 3], P = .03). The incidence of apoptosis in blastocysts cultured in HTF-SSS
      was significantly lower than those in HTF-alone group (mean +/- standard
      deviation 2.38 +/- 0.68 and 5.81 +/- 1.11, respectively, P = .001). CONCLUSION:
      Protein supplementation of culture media improves the hatching rate and reduces
      reactive oxygen species levels and the incidence of apoptosis in mouse
      preimplantation embryos.

PMID- 15738043
TI  - Fetal femur fracture and external cephalic version.

PMID- 15738044
TI  - Notice of a second report of the same case.

PMID- 15738045
TI  - ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician
      Gynecologists. Number 60, March 2005. Pregestational diabetes mellitus.

PMID- 15738046
TI  - Modulation of cardiac function: titin springs into action.

PMID- 15738047
TI  - The BKCa channel's Ca2+-binding sites, multiple sites, multiple ions.

PMID- 15738049
TI  - Divalent cation sensitivity of BK channel activation supports the existence of
      three distinct binding sites.
AB  - Mutational analyses have suggested that BK channels are regulated by three
      distinct divalent cation-dependent regulatory mechanisms arising from the
      cytosolic COOH terminus of the pore-forming alpha subunit. Two mechanisms account
      for physiological regulation of BK channels by microM Ca2+. The third may mediate
      physiological regulation by mM Mg2+. Mutation of five aspartate residues (5D5N)
      within the so-called Ca2+ bowl removes a portion of a higher affinity Ca2+
      dependence, while mutation of D362A/D367A in the first RCK domain also removes
      some higher affinity Ca2+ dependence. Together, 5D5N and D362A/D367A remove all
      effects of Ca2+ up through 1 mM while E399A removes a portion of low affinity
      regulation by Ca2+/Mg2+. If each proposed regulatory effect involves a distinct
      divalent cation binding site, the divalent cation selectivity of the actual site
      that defines each mechanism might differ. By examination of the ability of
      various divalent cations to activate currents in constructs with mutationally
      altered regulatory mechanisms, here we show that each putative regulatory
      mechanism exhibits a unique sensitivity to divalent cations. Regulation mediated
      by the Ca2+ bowl can be activated by Ca2+ and Sr2+, while regulation defined by
      D362/D367 can be activated by Ca2+, Sr2+, and Cd2+. Mn2+, Co2+, and Ni2+ produce
      little observable effect through the high affinity regulatory mechanisms, while
      all six divalent cations enhance activation through the low affinity mechanism
      defined by residue E399. Furthermore, each type of mutation affects kinetic
      properties of BK channels in distinct ways. The Ca2+ bowl mainly accelerates
      activation of BK channels at low [Ca2+], while the D362/D367-related high
      affinity site influences both activation and deactivation over the range of 10
      300 microM Ca2+. The major kinetic effect of the E399-related low affinity
      mechanism is to slow deactivation at mM Mg2+ or Ca2+. The results support the
      view that three distinct divalent-cation binding sites mediate regulation of BK
      channels.

PMID- 15738048
TI  - Phosphorylation of titin modulates passive stiffness of cardiac muscle in a titin
      isoform-dependent manner.
AB  - We investigated the effect of protein kinase A (PKA) on passive force in skinned
      cardiac tissues that express different isoforms of titin, i.e., stiff (N2B) and
      more compliant (N2BA) titins, at different levels. We used rat ventricular (RV),
      bovine left ventricular (BLV), and bovine left atrial (BLA) muscles (passive
      force: RV > BLV > BLA, with the ratio of N2B to N2BA titin, approximately 90:10,
      approximately 40:60, and approximately 10:90%, respectively) and found that N2B
      and N2BA isoforms can both be phosphorylated by PKA. Under the relaxed condition,
      sarcomere length was increased and then held constant for 30 min and the peak
      passive force, stress-relaxation, and steady-state passive force were determined.
      Following PKA treatment, passive force was significantly decreased in all muscle
      types with the effect greatest in RV, lowest in BLA, and intermediate in BLV.
      Fitting the stress-relaxation data to the sum of three exponential decay
      functions revealed that PKA blunts the magnitude of stress-relaxation and
      accelerates its time constants. To investigate whether or not PKA-induced
      decreases in passive force result from possible alteration of titin-thin filament
      interaction (e.g., via troponin I phosphorylation), we conducted the same
      experiments using RV preparations that had been treated with gelsolin to extract
      thin filaments. PKA decreased passive force in gelsolin-treated RV preparations
      with a magnitude similar to that observed in control preparations. PKA was also
      found to decrease restoring force in skinned ventricular myocytes of the rat that
      had been shortened to below the slack length. Finally, we investigated the effect
      of the beta-adrenergic receptor agonist isoprenaline on diastolic force in intact
      rat ventricular trabeculae. We found that isoprenaline phosphorylated titin and
      that it reduced diastolic force to a degree similar to that found in skinned RV
      preparations. Taken together, these results suggest that during beta-adrenergic
      stimulation, PKA increases ventricular compliance in a titin isoform-dependent
      manner.

PMID- 15738050
TI  - Photoreceptors of Nrl -/- mice coexpress functional S- and M-cone opsins having
      distinct inactivation mechanisms.
AB  - The retinas of mice null for the neural retina leucine zipper transcription
      factor (Nrl-/-) contain no rods but are populated instead with photoreceptors
      that on ultrastructural, histochemical, and molecular criteria appear cone like.
      To characterize these photoreceptors functionally, responses of single
      photoreceptors of Nrl-/- mice were recorded with suction pipettes at 35-37
      degrees C and compared with the responses of rods of WT mice. Recordings were
      made either in the conventional manner, with the outer segment (OS) drawn into
      the pipette ("OS in"), or in a novel configuration with a portion of the inner
      segment drawn in ("OS out"). Nrl-/- photoreceptor responses recorded in the OS
      out configuration were much faster than those of WT rods: for dim-flash responses
      tpeak = 91 ms vs. 215 ms; for saturating flashes, dominant recovery time
      constants, tau(D) = 110 ms vs. 240 ms, respectively. Nrl-/- photoreceptors in the
      OS-in configuration had reduced amplification, sensitivity, and slowed recovery
      kinetics, but the recording configuration had no effect on rod response
      properties, suggesting Nrl-/- outer segments to be more susceptible to damage.
      Functional coexpression of two cone pigments in a single mammalian photoreceptor
      was established for the first time; the responses of every Nrl-/- cell were
      driven by both the short-wave (S, lambda(max) approximately 360 nm) and the mid
      wave (M, lambda(max) approximately 510 nm) mouse cone pigment; the apparent ratio
      of coexpressed M-pigment varied from 1:1 to 1:3,000 in a manner reflecting a
      dorso-ventral retinal position gradient. The role of the G-protein receptor
      kinase Grk1 in cone pigment inactivation was investigated in recordings from Nrl
      /-/Grk1-/- photoreceptors. Dim-flash responses of cells driven by either the S-
      or the M-cone pigment were slowed 2.8-fold and 7.5-fold, respectively, in the
      absence of Grk1; the inactivation of the M-pigment response was much more
      seriously retarded. Thus, Grk1 is essential to normal inactivation of both S- and
      M-mouse cone opsins, but S-opsin has access to a relatively effective, Grk1
      independent inactivation pathway.

PMID- 15738051
TI  - Functional interactions between A' helices in the C-linker of open CNG channels.
AB  - Cyclic nucleotide-gated (CNG) channels are nonselective cation channels that are
      activated by the direct binding of the cyclic nucleotides cAMP and cGMP. The
      region linking the last membrane-spanning region (S6) to the cyclic nucleotide
      binding domain in the COOH terminus, termed the C-linker, has been shown to play
      an important role in coupling cyclic nucleotide binding to opening of the pore.
      In this study, we explored the intersubunit proximity between the A' helices of
      the C-linker regions of CNGA1 in functional channels using site-specific cysteine
      substitution. We found that intersubunit disulfide bonds can be formed between
      the A' helices in open channels, and that inducing disulfide bonds in most of the
      studied constructs resulted in potentiation of channel activation. This suggests
      that the A' helices of the C-linker regions are in close proximity when the
      channel is in the open state. Our finding is not compatible with a homology model
      of the CNGA1 C-linker made from the recently published X-ray crystallographic
      structure of the hyperpolarization-activated, cyclic nucleotide-modulated (HCN)
      channel COOH terminus, and leads us to suggest that the C-linker region depicted
      in the crystal structure may represent the structure of the closed state. The
      opening conformational change would then involve a movement of the A' helices
      from a position parallel to the axis of the membrane to one perpendicular to the
      axis of the membrane.

PMID- 15738052
TI  - Thymic output generates a new and diverse TCR repertoire after autologous stem
      cell transplantation in multiple sclerosis patients.
AB  - Clinical trials have indicated that autologous hematopoietic stem cell
      transplantation (HSCT) can persistently suppress inflammatory disease activity in
      a subset of patients with severe multiple sclerosis (MS), but the mechanism has
      remained unclear. To understand whether the beneficial effects on the course of
      disease are mediated by lympho-depletive effects alone or are sustained by a
      regeneration of the immune repertoire, we examined the long-term immune
      reconstitution in patients with MS who received HSCT. After numeric recovery of
      leukocytes, at 2-yr follow-up there was on average a doubling of the frequency of
      naive CD4(+) T cells at the expense of memory T cells. Phenotypic and T cell
      receptor excision circle (TREC) analysis confirmed a recent thymic origin of the
      expanded naive T cell subset. Analysis of the T cell receptor repertoire showed
      the reconstitution of an overall broader clonal diversity and an extensive
      renewal of clonal specificities compared with pretherapy. These data are the
      first to demonstrate that long-term suppression of inflammatory activity in MS
      patients who received HSCT does not depend on persisting lymphopenia and is
      associated with profound qualitative immunological changes that demonstrate a de
      novo regeneration of the T cell compartment.

PMID- 15738053
TI  - An immunoglobulin C kappa-reactive single chain antibody fusion protein induces
      tolerance through receptor editing in a normal polyclonal immune system.
AB  - Understanding immune tolerance mechanisms is a major goal of immunology research,
      but mechanistic studies have generally required the use of mouse models carrying
      untargeted or targeted antigen receptor transgenes, which distort lymphocyte
      development and therefore preclude analysis of a truly normal immune system. Here
      we demonstrate an advance in in vivo analysis of immune tolerance that overcomes
      these shortcomings. We show that custom superantigens generated by single chain
      antibody technology permit the study of tolerance in a normal, polyclonal immune
      system. In the present study we generated a membrane-tethered anti-Igkappa
      reactive single chain antibody chimeric gene and expressed it as a transgene in
      mice. B cell tolerance was directly characterized in the transgenic mice and in
      radiation bone marrow chimeras in which ligand-bearing mice served as recipients
      of nontransgenic cells. We find that the ubiquitously expressed, Igkappa-reactive
      ligand induces efficient B cell tolerance primarily or exclusively by receptor
      editing. We also demonstrate the unique advantages of our model in the genetic
      and cellular analysis of immune tolerance.

PMID- 15738054
TI  - Phosphorylation of histone deacetylase 7 by protein kinase D mediates T cell
      receptor-induced Nur77 expression and apoptosis.
AB  - The molecular basis of thymocyte negative selection, a crucial mechanism in
      establishing central tolerance, is not yet resolved. Histone deacetylases (HDACs)
      have emerged as key transcriptional regulators in several major developmental
      programs. Recently, we showed that the class IIa member, HDAC7, regulates
      negative selection by repressing expression of Nur77, an orphan nuclear receptor
      involved in antigen-induced apoptosis of thymocytes. Engagement of the T cell
      receptor (TCR) alleviates this repression through phosphorylation-dependent
      nuclear exclusion of HDAC7. However, the identity of the TCR-activated kinase
      that phosphorylates and inactivates HDAC7 was still unknown. Here, we demonstrate
      that TCR-induced nuclear export of HDAC7 and Nur77 expression is mediated by
      activation of protein kinase D (PKD). Indeed, active PKD stimulates HDAC7 nuclear
      export and Nur77 expression. In contrast, inhibition of PKD prevents TCR-mediated
      nuclear exclusion of HDAC7 and associated Nur77 activation. Furthermore, we show
      that HDAC7 is an interaction partner and a substrate for PKD. We identify four
      serine residues in the NH(2) terminus of HDAC7 as targets for PKD. More
      importantly, a mutant of HDAC7 specifically deficient in phosphorylation by PKD,
      inhibits TCR-mediated apoptosis of T cell hybridomas. These findings indicate
      that PKD is likely to play a key role in the signaling pathways controlling
      negative selection.

PMID- 15738055
TI  - Defective B cell tolerance checkpoints in systemic lupus erythematosus.
AB  - A cardinal feature of systemic lupus erythematosus (SLE) is the development of
      autoantibodies. The first autoantibodies described in patients with SLE were
      those specific for nuclei and DNA, but subsequent work has shown that individuals
      with this disease produce a panoply of different autoantibodies. Thus, one of the
      constant features of SLE is a profound breakdown in tolerance in the antibody
      system. The appearance of self-reactive antibodies in SLE precedes clinical
      disease, but where in the B cell pathway tolerance is first broken has not been
      defined. In healthy humans, autoantibodies are removed from the B cell repertoire
      in two discrete early checkpoints in B cell development. We found these
      checkpoints to be defective in three adolescent patients with SLE. 25-50% of the
      mature naive B cells in SLE patients produce self-reactive antibodies even before
      they participate in immune responses as compared with 5-20% in controls. We
      conclude that SLE is associated with abnormal early B cell tolerance.

PMID- 15738058
TI  - DNA microarray analysis of cranial sensory Ganglia identifies genes involved in
      somatosensation in craniofacial structures including oropharynx related to food
      intake.

PMID- 15738056
TI  - Defective NKT cell development in mice and humans lacking the adapter SAP, the X
      linked lymphoproliferative syndrome gene product.
AB  - SAP is an adaptor protein expressed in T cells and natural killer cells. It plays
      a critical role in immunity, as it is mutated in humans with X-linked
      lymphoproliferative syndrome (XLP), a fatal immunodeficiency characterized by an
      abnormal response to Epstein-Barr virus (EBV) infection. SAP interacts with the
      SLAM family receptors and promotes transduction signal events by these receptors
      through its capacity to recruit and activate the Src kinase FynT. Because it has
      been previously established that FynT is selectively required for the development
      of NKT cells, we examined NKT cells in SAP-deficient mice and in humans with XLP.
      In the absence of SAP, the development of NKT cells is severely impaired both in
      mice and in humans. These results imply that SAP is a potent regulator of NKT
      cell development. They also identify for the first time a defect in NKT cells
      associated with a human primary immunodeficiency, revealing a potential role of
      NKT cells in the immune response to EBV.

PMID- 15738059
TI  - Selective imaging of the receptor neuron population in the olfactory bulb of
      zebrafish and mice.

PMID- 15738060
TI  - Odor maps in the dorsal and lateral surfaces of the rat olfactory bulb.

PMID- 15738061
TI  - Odor perception is dynamic: consequences for interpretation of odor maps.

PMID- 15738062
TI  - Structural organization of the glomerulus in the main olfactory bulb.

PMID- 15738063
TI  - Signals regulating neurogenesis in the adult olfactory bulb.

PMID- 15738065
TI  - Adult neurogenesis and gliogenesis in the rat olfactory nervous system.

PMID- 15738064
TI  - Origin of the neocortical subependymal cells speculated by Emx1 and GAD67
      expression.

PMID- 15738066
TI  - In vivo imaging of migrating neurons in the mammalian forebrain.

PMID- 15738067
TI  - Analysis of neurogenesis using transgenic mice expressing GFP with nestin gene
      regulatory regions.

PMID- 15738068
TI  - Functional properties of adult-born juxtaglomerular cells in the mammalian
      olfactory bulb.

PMID- 15738069
TI  - cDNA microarray screening for taste-bud-specific genes.

PMID- 15738070
TI  - The roles of brain-derived neurotrophic factor in the development of nasal
      chemoreceptor neurons.

PMID- 15738071
TI  - A model for axon navigation based on glycocodes in the primary olfactory system.

PMID- 15738072
TI  - Expression of bHLH transcription factors and IGFs in the non-sensory patches,
      olfactory epithelium and vomeronasal organ.

PMID- 15738073
TI  - Postnatal development of the rat vomeronasal organ.

PMID- 15738074
TI  - A new surgical approach to the study of vomeronasal system regeneration.

PMID- 15738075
TI  - Restoring olfaction: a view from the olfactory epithelium.

PMID- 15738076
TI  - Regeneration and rewiring the olfactory bulb.

PMID- 15738077
TI  - Human body scents: conscious perceptions and biological effects.

PMID- 15738078
TI  - Augmentation of sensitivity to urinary pheromone and excreting of urinary
      pheromone by sexual experiences.

PMID- 15738079
TI  - Human bitter taste perception.

PMID- 15738080
TI  - Characterization of the primer pheromone molecules responsible for the 'male
      effect' in ruminant species.

PMID- 15738081
TI  - Chemosensory recognition of olfactory individuality.

PMID- 15738082
TI  - Olfactory subsystems in mammals: specific roles in recognizing chemical signals?

PMID- 15738083
TI  - Induction of c-Fos expression in mouse vomeronasal neurons by sex-specific non
      volatile pheromone(s).

PMID- 15738084
TI  - Vomeronasal mechanisms of mate recognition in mice.

PMID- 15738085
TI  - Long-term potentiation in the accessory olfactory bulb: a mechanism for olfactory
      learning.

PMID- 15738086
TI  - Developmental changes in olfactory behavior and limbic circuitry.

PMID- 15738087
TI  - Behavioral determination of odor preference is coded by the oscillation frequency
      in a collective oscillating network of a terrestrial mollusk.

PMID- 15738088
TI  - Neurobiology of taste-recognition memory formation.

PMID- 15738089
TI  - Amygdala-dependent mechanisms underlying memory retrieval of conditioned taste
      aversion.

PMID- 15738090
TI  - Functional interaction between TAS2R receptors and G-protein alpha subunits
      expressed in taste receptor cells.

PMID- 15738091
TI  - Hippocampus, temporal context and taste memories.

PMID- 15738092
TI  - Odor-intensity coding in the anterior piriform cortex.

PMID- 15738093
TI  - Chemotopic arrangement for taste quality discrimination in the cortical taste
      area.

PMID- 15738094
TI  - Functional reciprocal connections between olfactory and gustatory pathways.

PMID- 15738095
TI  - Involvement of forebrain glucose-monitoring neurons in taste information
      processing: electrophysiological and behavioral studies.

PMID- 15738096
TI  - Molecular mechanisms of sweet receptor function.

PMID- 15738097
TI  - ERP, fMRI and functional connectivity studies of brain response to odor in normal
      aging and Alzheimer's disease.

PMID- 15738098
TI  - Central olfactory pathway in response to olfactory stimulation in rats detected
      by magnetic resonance imaging.

PMID- 15738099
TI  - Representation of taste stimuli in the brain.

PMID- 15738100
TI  - Forebrain modulation of brainstem gustatory processing.

PMID- 15738101
TI  - Role played by vagal chemical sensors in the hepato-portal region and duodeno
      intestinal canal: an electrophysiological study.

PMID- 15738102
TI  - Reflex topography in the nucleus of the solitary tract.

PMID- 15738103
TI  - Peripheral signals in the control of feeding behavior.

PMID- 15738104
TI  - Chemical reception of fats in the oral cavity and the mechanism of addiction to
      dietary fat.

PMID- 15738106
TI  - Involvement of the mesolimbic system in palatability-induced ingestion.

PMID- 15738105
TI  - The role of orexigenic neuropeptides in the ingestion of sweet-tasting substances
      in rats.

PMID- 15738107
TI  - Taste receptor cells responding with action potentials to taste stimuli and their
      molecular expression of taste related genes.

PMID- 15738108
TI  - Medial orbitofrontal cortex: its role in mediating satiety in the macaque.

PMID- 15738109
TI  - Molecular mechanisms of trigeminal nociception and sensation of pungency.

PMID- 15738110
TI  - TRP channels and thermosensation.

PMID- 15738111
TI  - Coexpression of vanilloid receptor subtype-1 and acid-sensing ion channel genes
      in the human trigeminal ganglion neurons.

PMID- 15738112
TI  - Mechanisms of somatosensory neuronal sensitivity to alkaline pH.

PMID- 15738113
TI  - Gustatory effects of capsaicin that are independent of TRPV1 receptors.

PMID- 15738114
TI  - Lingual heat and cold sensitivity following exposure to capsaicin or menthol.

PMID- 15738115
TI  - Neural correlates of oral irritation by mustard oil and other pungent chemicals:
      a hot topic.

PMID- 15738116
TI  - Functional MRI of intranasal chemosensory trigeminal activation.

PMID- 15738117
TI  - Clinical studies of olfaction.

PMID- 15738118
TI  - Introductory remarks on umami research: candidate receptors and signal
      transduction mechanisms on umami.

PMID- 15738119
TI  - A new extension to the University of Erlangen Smell Test (UEST).

PMID- 15738120
TI  - A local steroid injection method for olfactory loss due to upper respiratory
      infection.

PMID- 15738122
TI  - The Odor Stick Identification Test for the Japanese (OSIT-J): clinical
      suitability for patients suffering from olfactory disturbance.

PMID- 15738121
TI  - Middle turbinate fenestration method: a new technique for the treatment of
      olfactory disturbance due to chronic sinusitis.

PMID- 15738123
TI  - Taste damage: previously unsuspected consequences.

PMID- 15738124
TI  - Taste disturbance and its recovery after middle ear surgery.

PMID- 15738125
TI  - Brain imaging studies of the functional organization of human olfaction.

PMID- 15738127
TI  - Location of the primary gustatory area in humans and its properties, studied by
      magnetoencephalography.

PMID- 15738126
TI  - Gender-specific olfactory sensitization: hormonal and cognitive influences.

PMID- 15738128
TI  - Temporal characteristics of human taste judgements as calibrations for gustatory
      event-related potentials and gustatory magnetoencephalographs.

PMID- 15738129
TI  - Regional expression patterns of T1r family in the mouse tongue.

PMID- 15738130
TI  - Cerebral imaging in taste.

PMID- 15738131
TI  - Flavor processing: perceptual and cognitive factors in multi-modal integration.

PMID- 15738132
TI  - Odor and taste interaction on brain responses in humans.

PMID- 15738133
TI  - Does olfactory memory depend on remembering odors?

PMID- 15738134
TI  - Persistence of acquired changes in the properties of odors and flavors for both
      humans and rats.

PMID- 15738135
TI  - Complex taste--taste of D-amino acids.

PMID- 15738137
TI  - The effect of visual images on perception of odors.

PMID- 15738136
TI  - Understanding the origin of flavor preferences.

PMID- 15738138
TI  - Odor, information and new cosmetics--the ripple effect on life by aromachology
      research.

PMID- 15738139
TI  - Effects of fragrance on emotions: moods and physiology.

PMID- 15738140
TI  - Cloning and characterization of a novel mGluR1 variant from vallate papillae that
      functions as a receptor for L-glutamate stimuli.

PMID- 15738141
TI  - Odor-associative learning and emotion: effects on perception and behavior.

PMID- 15738142
TI  - 'Electronic nose'--new condition monitoring devices for environmental
      applications.

PMID- 15738143
TI  - Study of odor recorder for dynamical change of odor.

PMID- 15738144
TI  - Taste sensor.

PMID- 15738145
TI  - A voltammetric electronic tongue.

PMID- 15738146
TI  - Sensor fusion for taste sensor and odor sensor.

PMID- 15738147
TI  - Green odor reduces pain sensation and fatigue-like responses without affecting
      sensorimotor function.

PMID- 15738148
TI  - Effects of plant-derived odors on sleep-wakefulness and circadian rhythmicity in
      rats.

PMID- 15738149
TI  - Effects of green odor on expression of Fos-immunoreactivity in the
      paraventricular nucleus of the thalamus in forced swimming rats.

PMID- 15738150
TI  - Prevention and/or recovery effects by green odor(s) on fatigue and green-odor
      responsible brain regions as revealed by PET.

PMID- 15738151
TI  - Expression of phospholipase C-beta4 in rat circumvallate taste buds.

PMID- 15738152
TI  - Function and expression of the Drosophila gr genes in the perception of sweet,
      bitter and pheromone compounds.

PMID- 15738153
TI  - Revisited roles of Drosophila female pheromones.

PMID- 15738154
TI  - Trehalose sensitivity of the gustatory receptor neurons expressing wild-type,
      mutant and ectopic Gr5a in Drosophila.

PMID- 15738155
TI  - Stereospecificity of the receptor site for glycerol, a new sweetener, in a
      labellar sugar receptor cell of Drosophila.

PMID- 15738156
TI  - Taste modulators are tools to gain a better insight into specific sensitivity of
      chemoreceptors in blowflies.

PMID- 15738157
TI  - The nitric oxide-cyclic GMP cascade in sugar receptor cells of the blowfly,
      Phormia regina.

PMID- 15738158
TI  - Making scents out of spatial and temporal codes in specialist and generalist
      olfactory networks.

PMID- 15738159
TI  - Neural basis of odor-source searching behavior in insect brain systems evaluated
      with a mobile robot.

PMID- 15738160
TI  - Odor-modulated navigation in insects and artificial systems.

PMID- 15738161
TI  - Feeding behavior regulation in the fly: effect of a noxious substance through the
      taste and olfactory neurons.

PMID- 15738162
TI  - Multiple pathways for signaling glutamate taste in rodents.

PMID- 15738163
TI  - Diversity of odorant-binding proteins and chemosensory proteins in insects.

PMID- 15738164
TI  - Chemosensory basis of host recognition in butterflies--multi-component system of
      oviposition stimulants and deterrents.

PMID- 15738166
TI  - Innate and changed responses to plant odours in moths and weevils.

PMID- 15738165
TI  - Sensory flexibility in hawkmoth foraging behavior: lessons from Manduca sexta and
      other species.

PMID- 15738167
TI  - Formation of long-term olfactory memory in the cricket Gryllus bimaculatus.

PMID- 15738168
TI  - Outline of a theory of olfactory processing and its relevance to humans.

PMID- 15738169
TI  - Odor coding in projection neurons of the honeybee brain.

PMID- 15738170
TI  - Feeding behavior in scyphozoa, crustacea and cephalopoda.

PMID- 15738171
TI  - The role of chemical signals in the social behavior of crayfish.

PMID- 15738173
TI  - Urine as a social signal in the mozambique tilapia (Oreochromis mossambicus).

PMID- 15738174
TI  - Downstream signaling effectors for umami taste.

PMID- 15738172
TI  - Potential multiple functions of a male sea lamprey pheromone.

PMID- 15738175
TI  - Olfactory receptor neurons in fish: structural, molecular and functional
      correlates.

PMID- 15738176
TI  - Correlations between olfactory discrimination, olfactory receptor neuron
      responses and chemotopy of amino acids in fishes.

PMID- 15738177
TI  - Second messenger systems mediating sex pheromone and amino acid sensitivity in
      goldfish olfactory receptor neurons.

PMID- 15738178
TI  - Processing of odor information in the olfactory bulb and cerebral lobes.

PMID- 15738179
TI  - Factors contributing to individual differences in sucrose preference.

PMID- 15738180
TI  - Cellular mechanisms of olfactory signal transduction.

PMID- 15738181
TI  - Signal transduction of umami taste: insights from knockout mice.

PMID- 15738182
TI  - Gap junctions among taste bud cells in mouse fungiform papillae.

PMID- 15738183
TI  - Communication routes within the taste bud by neurotransmitters and neuropeptides.

PMID- 15738184
TI  - Mouse taste buds release serotonin in response to taste stimuli.

PMID- 15738185
TI  - Acetylcholine and acetylcholine receptors in taste receptor cells.

PMID- 15738187
TI  - Sodium-level-sensitive sodium channel and salt-intake behavior.

PMID- 15738186
TI  - A novel vanilloid receptor-1 (VR-1) variant mammalian salt taste receptor.

PMID- 15738188
TI  - Lectin histochemistry of taste buds in the circumvallate papilla of the rat.

PMID- 15738189
TI  - Regulation of taste bud cell differentiation by notch signaling pathway.

PMID- 15738190
TI  - Shh signaling and regulatory gene expression in mouse taste buds.

PMID- 15738191
TI  - Development of gustatory organs and innervating sensory ganglia.

PMID- 15738192
TI  - Cell types and lineages in taste buds.

PMID- 15738193
TI  - Developmental changes of the taste sensation depending on the maturation of the
      taste bud and its distribution in mammals.

PMID- 15738194
TI  - Development of the vagal taste system of goldfish.

PMID- 15738195
TI  - Individual differences and the chemical senses.

PMID- 15738197
TI  - Recovery of salt taste responses and PGP 9.5 immunoreactive taste bud cells
      during regeneration of the mouse chorda tympani nerve.

PMID- 15738196
TI  - Synaptic connections in developing and adult rat taste buds.

PMID- 15738198
TI  - Nerve-target interactions in the gustatory system following unilateral chorda
      tympani nerve section.

PMID- 15738199
TI  - The functional consequences of gustatory nerve regeneration as assessed
      behaviorally in a rat model.

PMID- 15738201
TI  - Neurobiology of the gustatory-salivary reflex.

PMID- 15738200
TI  - What the tongue tells the brain about taste.

PMID- 15738202
TI  - Neural mechanism and possible role of inhibition of gastric motility induced by
      superior laryngeal afferents.

PMID- 15738203
TI  - Posterior insular cortex in rats: response characteristics and function.

PMID- 15738204
TI  - Taste and related systems in primates including humans.

PMID- 15738205
TI  - Possible changes in information from the primary to higher-order gustatory
      cortices, studied by recording neural activities during a taste discrimination
      GO/NOGO task in monkeys.

PMID- 15738206
TI  - The many flavors of temporal coding in gustatory cortex.

PMID- 15738207
TI  - Genetic approach to characterize interaction of sweeteners with sweet taste
      receptors in vivo.

PMID- 15738208
TI  - The role of the dpa locus in mice.

PMID- 15738209
TI  - Micro and macro models of the sweet receptor.

PMID- 15738210
TI  - Brazzein a small, sweet protein: discovery and physiological overview.

PMID- 15738212
TI  - Axon guidance of olfactory sensory neurons in zebrafish.

PMID- 15738211
TI  - Brazzein, a small, sweet protein: effects of mutations on its structure, dynamics
      and functional properties.

PMID- 15738213
TI  - Development of wiring specificity of the Drosophila olfactory system.

PMID- 15738214
TI  - Functional expression of Mammalian odorant receptors.

PMID- 15738215
TI  - Odorant receptor specificities and receptor combinatorials: implications for
      olfactory coding.

PMID- 15738216
TI  - Negative feedback regulation ensures the one neuron-one receptor rule in the
      mouse olfactory system.

PMID- 15738217
TI  - Invited review: methods for the screening, isolation, and characterization of
      exopolysaccharides produced by lactic acid bacteria.
AB  - The ability to produce exopolysaccharides (EPS) is widespread among lactic acid
      bacteria (LAB), although the physiological role of these molecules has not been
      clearly established yet. Some EPS confer on LAB a "ropy" character that can be
      detected in cultures that form long strands when extended with an inoculation
      loop. When EPS are produced in situ during milk fermentation they can act as
      natural biothickeners, giving the product a suitable consistency, improving
      viscosity, and reducing syneresis. In addition, some of these EPS may have
      beneficial effects on human health. The increasing demand by consumers of novel
      dairy products requires a better understanding of the effect of EPS on existing
      products and, at the same time, the search for new EPS-producing strains with
      desirable properties. The use of genetically modified organisms capable of
      producing high levels of EPS or newly designed biopolymers is still very limited.
      Therefore, exploration of the biodiversity of wild LAB strains from natural
      ecological environments is currently the most suitable approach to search for the
      desired EPS-phenotype. The screening of ropy strains and the isolation and
      characterization of EPS responsible for this characteristic have led to the
      application over the past years of a wide variety of techniques. This review
      summarizes the available information on methods and procedures used for research
      on this topic. The information provided deals with methods for screening of EPS
      producing LAB, detection of the ropy phenotype, and the physicochemical and
      structural characterization of these molecules, including parameters related to
      their viscosifying properties. To our knowledge, this is the first compilation of
      methods available for the study of EPS produced by LAB.

PMID- 15738218
TI  - Short communication: comparison of covered and uncovered Schreiber test for
      cheese meltability evaluation.
AB  - Schreiber meltability tests were performed on glass Petri dishes, with and
      without the Petri dish cover placed over the cheese samples, at 100, 150, and 232
      degrees C. Meltability of different process cheese and Cheddar cheese samples was
      determined based on the melt spread distance and area. At the test temperature of
      232 degrees C, the covered Schreiber was significantly superior to the uncovered
      test because of no crust formation, no browning, and a circular melting pattern,
      which were attributed to the barrier effect of covering the cheese samples (which
      inhibits moisture loss during the test). The covered Schreiber test data were
      statistically more robust as measured by the lower average coefficient of
      variation than the data from the traditional uncovered Schreiber test.

PMID- 15738219
TI  - Physical properties of ice cream containing milk protein concentrates.
AB  - Two milk protein concentrates (MPC, 56 and 85%) were studied as substitutes for
      20 and 50% of the protein content in ice cream mix. The basic mix formula had 12%
      fat, 11% nonfat milk solids, 15% sweetener, and 0.3% stabilizer/emulsifier blend.
      Protein levels remained constant, and total solids were compensated for in MPC
      mixes by the addition of polydextrose. Physical properties investigated included
      apparent viscosity, fat globule size, melting rate, shape retention, and freezing
      behavior using differential scanning calorimetry. Milk protein concentrate
      formulations had higher mix viscosity, larger amount of fat destabilization,
      narrower ice melting curves, and greater shape retention compared with the
      control. Milk protein concentrates did not offer significant modifications of ice
      cream physical properties on a constant protein basis when substituted for up to
      50% of the protein supplied by nonfat dry milk. Milk protein concentrates may
      offer ice cream manufacturers an alternative source of milk solids non-fat,
      especially in mixes reduced in lactose or fat, where higher milk solids nonfat
      are needed to compensate other losses of total solids.

PMID- 15738220
TI  - Effect of antioxidant (alpha-tocopherol and ascorbic acid) fortification on light
      induced flavor of milk.
AB  - The effectiveness of added antioxidants against oxidation off-flavor development
      in light-exposed milk was evaluated using sensory and chemical analysis. Sensory
      testing for similarity showed no perceivable difference between control milk and
      milk with added (1) 0.05% alpha-tocopherol (TOC) and (2) 0.025% alpha-tocopherol
      and 0.025% ascorbic acid (TOC/ASC), but did demonstrate a perceivable difference
      when adding (3) 0.05% ascorbic acid (ASC) alone. Subsequently, sensory testing
      for difference showed a significant difference in oxidation off-flavor between
      light-exposed control milk and light-exposed milk with added TOC/ASC, whereas
      milk fortified with TOC was not different from control. Gas chromatography
      olfactometry showed that more aroma-active flavor compounds were observed in
      light-exposed milk treated with TOC and TOC/ASC than light-exposed milk with no
      added antioxidants. The thiobarbituric acid reactive substances (TBARS) test
      verified chemically the extent of oxidation in control and antioxidant-treated
      milk samples. Milk that was exposed to light for 10 h showed a significantly
      higher TBARS value (0.92 +/- 0.09 mg/kg) than milk that was protected from light
      (0.59 +/- 0.184 mg/kg), or milk that was treated with TOC/ASC (0.26 +/- 0.092
      mg/kg). Direct addition of low levels of antioxidants (TOC/ASC) to milk protected
      its flavor over 10 h of light exposed storage.

PMID- 15738221
TI  - Aroma analysis of light-exposed milk stored with and without natural and
      synthetic antioxidants.
AB  - The effect of antioxidants, added in a single initial dose or in weekly additions
      to extended shelf life milk, was evaluated over 6 wk of lighted storage at 4
      degrees C. Light-induced oxidation was measured by determining pentanal, hexanal,
      heptanal, and 1-octen-3-ol contents. Weekly addition of a combination of
      butylated hydroxyanisole and butylated hydroxytoluene (100 mg/kg of milk fat,
      each) maintained heptanal content of milk at levels comparable to light-protected
      milk, whereas an initial single addition of alpha-tocopherol significantly
      decreased hexanal content over the first 4 wk of storage. Odor-active compounds
      associated with light-induced oxidation included 2,3-butanedione, pentanal,
      dimethyl disulfide, hexanal, 1-hexanol, heptanal, 1-heptanol, and nonanal. The
      addition of butylated hydroxyanisole and butylated hydroxytoluene in a single
      initial addition resulted in decreases in pentanal and hexanal odor, but not in
      heptanal and 1-heptanol odor, whereas the addition of alpha-tocopherol and
      ascorbyl palmitate decreased pentanal and heptanol odor, but not hexanal and
      heptanal odor.

PMID- 15738222
TI  - Effects of sterilization, packaging, and storage on vitamin C degradation,
      protein denaturation, and glycation in fortified milks.
AB  - Monitoring the nutritional quality of dietetic milk throughout its shelf life is
      particularly important due to the high susceptibility of some vitamins to
      oxidation, and the continuous development of the Maillard reaction during
      storage. The objective of this paper was to evaluate the vitamin C content and
      protein modification by denaturation and glycation on fortified milk samples
      (growth milks) destined for 1- to 3-yr-old children. The influences of the
      sterilization process, formulation, packaging, and storage duration at ambient
      temperature in the dark were studied. Vitamin C degradation was particularly
      influenced by type of packaging. The use of a 3-layered opaque bottle was
      associated with complete oxidation of vitamin C after 1 mo of storage, whereas in
      the 6-layered opaque bottle, which has an oxygen barrier, the vitamin C content
      slowly decreased to reach 25% of the initial concentration after 4 mo of storage.
      However, no significant effect of vitamin C degradation during storage could be
      observed in terms of Maillard reaction, despite the fact that a probable impact
      occurred during sterilization. Furosine content and the FAST (fluorescence of
      advanced Maillard products and soluble tryptophan) index-indicators of the early
      and advanced Maillard reaction, respectively-were significantly higher in the in
      bottle sterilized milk samples compared with UHT samples, and in fortified milk
      samples compared with cow milk. However, after 1 mo, the impact of storage was
      predominant, increasing the furosine level and the FAST index at similar levels
      for the differently processed samples. The early Maillard reaction developed
      continuously throughout the storage period.In conclusion, only packaging
      comprising an oxygen and light barrier is compatible with vitamin C fortification
      of milk. Furthermore, short storage time or low storage temperature is needed to
      retard vitamin C degradation, protein denaturation, and development of the
      Maillard reaction.

PMID- 15738223
TI  - Lactococcal 936-species phage attachment to surface of Lactococcus lactis.
AB  - The interactions of the 936-species phages sk1, jj50, and 64 with the cell
      surface of Lactococcus lactis LM0230 were analyzed. Cell envelopes (walls +
      plasma membrane), cell wall, or plasma membrane from L. lactis ssp. lactis LM0230
      each inactivated the phages in vitro. However, other 936-species phages kh and
      P008, which do not infect strain LM0230, were not inactivated by any of the
      subcellular fractions. Treating cell walls or plasma membrane with the cell wall
      hydrolase mutanolysin eliminated inactivation of phage sk1. This suggested that
      intact cell wall fragments were required for inactivation. A role for plasma
      membrane in phage sk1 inactivation was further investigated. Boiling, washing in
      2 M KCl, 8 M urea, or 0.1 M Na(2)CO(3)/pH 11, or treating the plasma membrane
      with proteases did not reduce adsorption or inactivation of phage. Adding
      lipoteichoic acid or antibodies to lipoteichoic acid did not reduce inactivation
      of phage in a mixture with membrane, suggesting that lipoteichoic acid was not
      involved. Inactivation by envelopes or cell wall correlated with ejection of DNA
      from the phage sk1 capsid. Although calcium is required for plaque formation, it
      was not required for adsorption, inactivation, or ejection of phage DNA by
      envelopes or cell wall. The results suggest that at least for phages sk1, jj50,
      and 64, adsorption and phage DNA injection into the host does not require a host
      membrane protein or lipoteichoic acid, and that cell wall components are
      sufficient for these initial steps of phage infection.

PMID- 15738224
TI  - False-positive outcome and drug residue in milk samples over withdrawal times.
AB  - This study was conducted to identify false-positive outcomes and drug residues in
      milk samples over withdrawal times and to determine whether the positive results
      were caused by drug residues or natural inhibitors. A total of 73 milk samples
      over withdrawal times after the last intramammary infusion were collected from
      each treated quarter of cows and tested using the Delvotest SP assay. Reading
      time was 150, 165, and 180 min, and results of samples were recorded according to
      the color of the well containing the control milk sample. There were 24, 20, and
      12 positive samples at the reading times of 150, 165, and 180 min, respectively.
      All 24 positive milk samples were heated at 82 degrees C for 5 min and retested
      to verify that the positive results were caused by drug residues or natural
      inhibitors. Twenty-one samples that exhibited positive results were negative
      after heat treatment, and drug residues were not identified by LacTek and Charm
      tests. However, 3 samples that exhibited positive results from heat treatment of
      82 degrees C were positive for drugs. In our study, most positive results (89%)
      in the milk samples over withdrawal times were false-positive results by natural
      inhibitors. Moreover, the heat treatment is a fast, simple, and inexpensive
      method to remove false-positive results and has no effect on positive samples
      containing drugs. We suggest that heat treatment before screening tests is an
      effective way to reduce false-positive results in the milk samples.

PMID- 15738225
TI  - Pregnancy rates in lactating dairy cows after presynchronization of estrous
      cycles and variations of the Ovsynch protocol.
AB  - Our objectives were to determine pregnancy rates after altering times of the
      second GnRH injection, insemination, or both in a combined Presynch + Ovsynch
      protocol, to accommodate once-daily lockup of dairy cows. Lactating dairy cows (n
      = 665) from 2 dairy herds in northeastern Kansas were studied. Cows ranged from
      24 to 44 d in milk (DIM) at the start of the Pre-synch protocol, which consisted
      of 2 injections of PGF(2alpha) 14 d apart, with the second injection given 12 d
      before initiating the Ovsynch protocol. Cows were blocked by lactation number and
      assigned randomly to 3 treatments consisting of variations of the Ovsynch
      protocol. Cows in 2 treatments received injections of GnRH 7 d before and 48 h
      (G48) after the PGF(2alpha) injection. Timed AI (TAI) was conducted at the time
      of the second GnRH injection (G48 + TAI48) or 24 h later (G48 + TAI72). Cows in
      the third treatment received the injections of GnRH 7 d before and at 72 h after
      PGF(2alpha) and were inseminated at the time of the second GnRH injection (G72 +
      TAI72). Pregnancy was diagnosed weekly by palpation per rectum of uterine
      contents on d 40 or 41 after TAI. Pregnancy rates differed between herds, but
      they were consistently greater for G72 + TAI72 than for G48 + TAI48 and G72 +
      TAI72. Subsequent calving rates were consistent with differences in initial TAI
      pregnancy rates. Pregnancy loss was least for cows on the G72 + TAI72 treatment.
      Body condition scores (BCS) ranged from 1.0 to 4.0 when assessed on Monday of the
      breeding week. An interaction of BCS and herd was detected in which cows in herd
      1 having poorer BCS (<2.25) had greater pregnancy rates than cows of greater BCS
      (>/=2.25), whereas the reverse was true in herd 2 in which overall pregnancy
      rates were greater. We concluded that inseminating at 48 or 72 h after
      PGF(2alpha), when GnRH was administered at 48 h after PGF(2alpha), produced fewer
      pregnancies than inseminating and injecting GnRH at 72 h after PGF(2alpha) for
      cows whose estrous cycles were synchronized before initiating this variant of the
      Ovsynch protocol.

PMID- 15738226
TI  - Timing of inhibitory actions of gossypol on cultured bovine embryos.
AB  - Culture of bovine preimplantation embryos with gossypol, a polyphenolic pigment
      in cottonseed, inhibits development. Neither stage at which embryos are most
      sensitive to gossypol, nor the mechanism by which development is blocked is
      known. Our objectives were to characterize stages at which gossypol inhibits
      embryonic development and evaluate involvement of apoptosis in actions of
      gossypol. When presumptive 1-cell embryos were cultured continuously in medium
      containing gossypol at concentrations of 0, 2.5, 5, and 10 microg/mL, cleavage
      rate was not reduced by any concentration of gossypol, but percentages of 1-cell
      embryos that became blastocysts 8 d after insemination was reduced by the 10
      microg/mL dose of gossypol. Culture of presumptive 1-cell embryos with gossypol
      at 10 microg/mL for 24 h was not sufficient to block development. Furthermore,
      gossypol did not affect development to the blastocyst stage when 2-cell embryos
      were cultured with gossypol at 10 microg/mL for 24 h or 7 d. Culture of embryos >
      or =16 cells with gossypol at 10 microg/mL for 24 h failed to reduce cell number
      24 h later or increase blastomere apoptosis. Results indicate that embryonic
      development can be disrupted by long-term exposure to gossypol at 10 microg/mL
      and that exposure at the 1-cell stage is required. Thus, it is likely that the
      deleterious effects of gossypol involve disruption of events at the 1-cell stage
      and such effects are reversible if gossypol is removed. After the 1-cell stage,
      gossypol does not affect development because the critical event that gossypol
      disrupts occurs at the 1-cell stage only or the embryo develops cytoprotective
      mechanisms after the 1-cell stage that limit actions of gossypol.

PMID- 15738228
TI  - Impact of early lactation somatic cell count in heifers on milk yield over the
      first lactation.
AB  - The objective of this study was to estimate the impact of somatic cell count
      (SCC) in early lactation (SCCel) [measured between 5 to 14 d in milk (DIM)] of
      dairy heifers on test-day milk yield (MY) during the first lactation. In total,
      117,496 four-weekly test-day records of 14,243 heifers were used. A multilevel
      regression analysis, which included test-day SCC among the explanatory variables,
      revealed that an increase by one unit of the natural log-transformed SCCel
      (LnSCCel) was on average associated with a decrease in MY of 0.13 kg/d later in
      lactation. As an example, a heifer with an SCCel of 50,000 cells/mL measured at
      10 DIM was estimated to produce 119 and 155 kg more milk during its first
      lactation than heifers with a SCCel of 500,000 and 1,000,000 cells/mL,
      respectively. When not accounting for test-day SCC, the effect of LnSCCel on MY
      was larger, indicating that part of the negative impact of elevated SCCel was
      associated with elevated test-day SCC later in lactation.Furthermore, an elevated
      SCCel at 14 DIM had a larger impact than an equally elevated SCCel measured at an
      earlier DIM. In addition, the negative effect of an elevated SCCel remained
      present during almost the entire first lactation in a subgroup of heifers with a
      second test-day SCC </=50,000 cells/mL, suggesting that prevention rather than
      cure of an elevated SCCel should be preferred. This study stresses the importance
      of heifers having low SCCel, as an elevated SCCel will negatively affect milk
      production during the first lactation, probably via impairment of mammary
      function and, to a smaller extent, via elevated test-day SCC later in lactation.

PMID- 15738227
TI  - Effect of eprinomectin treatment at calving on milk production in dairy herds
      with limited outdoor exposure.
AB  - The objective of this study was to determine the effect of anthelmintic treatment
      at calving in herds that were totally or semiconfined during the summer. In
      totally confined herds, lactating and dry cows were housed throughout the summer
      and had no access to pasture. In semiconfined herds, lactating and dry cows had
      limited outdoor exposure to a small pasture or paddock but were still fed a
      ration that met all their nutritional requirements. The study was carried out
      between February 2002 and February 2003 in 65 herds enrolled with DHI and
      distributed in 4 regions in Canada and 1 state in the United States. Cows were
      randomly allocated to receive eprinomectin or a placebo, with treatment being
      administered on or close to day of calving. In May and June 2002, 8 fecal samples
      were collected from each farm and fecal egg counts (FEC) were determined. Monthly
      bulk tank milk samples from each farm were tested with an indirect ELISA using a
      crude Ostertagia ostertagi antigen. Monthly test-day milk production data were
      recorded for 200 d after calving. In general, FEC were very low (mean = 1 egg per
      gram, range = 0 to 27). Mean herd bulk milk ELISA optical density ratio (ODR)
      values for the whole year ranged between 0.22 and 0.80. The ODR values were
      dichotomized into high and low using a threshold of 0.5. Treatment effects were
      analyzed using a linear mixed model with herd and cow as random effects. The
      analysis was restricted to 4789 cows (23,956 test-day records) treated between 21
      d before and 7 d after calving. Overall, there was no significant effect of
      treatment. However, there was a tendency for an interaction between treatment and
      ODR, as illustrated by a larger numerical difference in treated vs. untreated
      cows in high-ODR herds than in low-ODR herds. However, the confidence intervals
      for the treatment effects (kg/d of milk per cow) in high-ODR herds (-0.33 to
      1.10) and in low-ODR herds (-0.53 to 0.14) were wide and included zero.
      Therefore, this study failed to show a beneficial effect of eprinomectin
      treatment in these totally or semiconfined herds.

PMID- 15738229
TI  - Pregnancy rates and milk production in natural service and artificially
      inseminated dairy herds in Florida and Georgia.
AB  - Effects of artificial insemination (AI) and natural service (NS) breeding systems
      on pregnancy rates (PR) by stage of lactation, season, and changes in milk
      production over time were examined using lactation and herd DHIA records of
      Holstein cows in dairy herds located in Florida and Georgia. The reported genetic
      profile of service sires of the herd was used to determine the percentage of cows
      bred to natural service bulls (%NS). Two seasons were considered: winter
      (November-April) and summer (May-October) from 1995 to 2002 (16 periods). Herd
      periods were assigned 1 of 3 breeding systems: AI (0 to 10% NS), mixed (11 to 89%
      NS) and NS (90 to 100% NS). Seventy percent of the herds used NS bulls as a
      component of their breeding system during the study period. The PR during winter
      (17.9%) was greater than that during summer (9.0%). During winter, PR for AI
      herds (17.9%) did not differ from that for mixed (17.8%) and NS herds (18.0%).
      During summer, PR for AI herds (8.1%) was slightly less than that for mixed
      (9.3%) and NS herds (9.8%). During winter, PR for cows at 71 to 91 d, 92 to 112
      d, and 113 to 133 d in milk were 1.4% lower for mixed herds compared with AI and
      NS. Pregnancy rate for NS herds was 2.6% lower during late lactation compared
      with AI and mixed herds. During summer, PR for cows at 71 to 91 and 92 to 112 d
      in milk were 2.6 and 1.8% greater, respectively, for NS herds compared with AI.
      However, from 260 to 364 d in milk, PR for NS herds was less than that for AI and
      mixed herds. No significant interaction was detected between breeding system and
      lactation number. Rolling herd average milk production during the study period
      was less in the NS herds (7180 kg) compared with AI (8513 kg) and mixed herds
      (8176 kg), but the annual change in milk production was not different among
      breeding systems. The results indicated that use of NS bulls did not result in
      meaningful disadvantages in terms of PR and changes in milk production over time.

PMID- 15738230
TI  - Use of intravaginal progesterone-releasing inserts in a synchronization protocol
      before timed AI and for synchronizing return to estrus in Holstein heifers.
AB  - Holstein heifers (n = 189) were submitted to a 42-d artificial insemination (AI)
      period in which they underwent AI after once-daily evaluation of rubbed tail
      chalk. At the onset of the AI period (d 0), heifers were assigned randomly to
      receive synchronization of ovulation and timed AI (TAI; d 0: 100 mug of GnRH; d
      6: 25 mg of PGF(2alpha); d 8: 100 mug of GnRH + TAI) either without (GPG; n =
      95), or with inclusion of a CIDR insert (CIDR; n = 94) from d 0 to 6. No CIDR
      heifers received AI before d 8 compared with 24% of GPG heifers, and pregnancy
      rate per AI (PR/AI) at 30 d after TAI did not differ between treatments. To
      synchronize return to estrus for heifers failing to conceive after TAI, heifers
      (n = 166) receiving TAI to first service were randomly assigned to receive no
      further treatment (control; n = 85) or receive a new CIDR insert between 14 and
      20 d after TAI (Resynch; n = 81). No Resynch heifers received AI during CIDR
      treatment compared with 35% of control heifers, and the proportion of heifers
      receiving AI within 72 h after the day of CIDR removal was 78 vs. 50% for Resynch
      vs. control heifers, respectively. No treatment x inseminator interaction was
      detected at first or second AI; however, overall PR/AI was modest for heifers
      throughout the experiment due to poor performance of 2 of the 3 herd inseminators
      (14, 6, and 58% PR/AI, respectively). Inclusion of CIDR inserts suppressed estrus
      during the TAI protocol with no reduction in PR/ AI. Resynchronization of estrus
      using CIDR inserts resulted in tighter synchrony of estrus among nonpregnant
      heifers compared with untreated controls.

PMID- 15738231
TI  - Factors of variation influencing bulk tank somatic cell count in dairy sheep.
AB  - Between January and December 2002, a total of 21,685 records for bulk tank milk
      somatic cell count (BTSCC) were obtained from 309 dairy ewe herds belonging to
      the Sheep Improvement Consortium in Castilla-Leon, Spain. Based on the first
      statistical model, ANOVA detected significant effects of herd, breed, month
      within herd, dry therapy, type of milking, contagious agalactia, and
      installations within machine milking on logBTSCC. A second statistical model was
      used on herds with machine milking to study the effect of the vacuum level and
      pulsation rate on BTSCC. Herd and month within herd were important variation
      factors as they explained 48.4 and 16.1% of the variance in BTSCC. Variability in
      logBTSCC among breeds ranged from 5.84 (Castellana) to 6.09 (Awassi and Spanish
      Assaf). Implementing dry-ewe therapy (5.91) significantly reduced logBTSCC
      compared with when it was not implemented (6.10). Hand milking elicited greater
      logBTSCC (6.07) than machine milking (5.94). Machine milking of ewes in milking
      parlors (logBTSCC: 5.88 to 5.94) was associated with better udder health than was
      the use of bucket-milking machines (6.04). Reduced vacuum levels and elevated
      pulsation rate during machine milking optimized BTSCC. In all cases, clinical
      outbreaks of contagious agalactia increased BTSCC. As a result, dry therapy was
      proposed as the main tool to reduce BTSCC. Optimization of milking-machine
      standards and parlor systems also improved udder health in dairy sheep.

PMID- 15738232
TI  - Mammary cell turnover and enzyme activity in dairy cows: effects of milking
      frequency and diet energy density.
AB  - The aim of the study was to investigate the effects of diet energy density and
      milking frequency on mammary cell turnover and synthetic capacity in dairy cows.
      Experiment 1 used 20 dairy cows. From d 4 to wk 16 postpartum, the cows were fed
      either a low-energy density or a high-energy density diet. From d 4 through wk 8,
      half of the cows in each group were milked 3 times (3x) or 2 times (2x) daily.
      From wk 9 to 16, all cows were milked 2 times daily. Mammary biopsies were
      obtained at wk 8 and 16 postpartum. In experiment 2, udders of 18 individual cows
      were milked diagonally 2x and 4x, and biopsies were obtained after 7 d. In
      experiment 1, cows on the low-energy density diet yielded 17 and 24% less milk
      during wk 3 to 8 and wk 11 to 16 postpartum, respectively. Furthermore, at 8 wk
      postpartum, mammary enzyme activities tended to be lower and mammary cell
      proliferation was lower in cows on the low-energy density diet. Three times daily
      milking during the first 8 wk postpartum resulted in 11% higher milk yield.
      Mammary cell turnover or enzyme activities were not significantly affected at 8
      wk. The 3x milking for 8 wk resulted only in a transient carryover effect on milk
      yield and neither cell turnover nor enzyme activities were significantly affected
      at 16 wk postpartum. In experiment 2, mammary cell turnover and enzyme activity
      were unaffected after 7 d of 4x milking although milk yield increased by 18%. We
      conclude that nutrient restriction affects mammary cell turnover and possible
      enzyme activity, and that tuning of negative feedback loops in response to
      filling of the gland may be the dominating effects of changes in milking
      frequency.

PMID- 15738233
TI  - Effects of feeding propionate and calcium salts of long-chain fatty acids on
      transition dairy cow performance.
AB  - Multiparous Holstein cows (n = 40) were used in a randomized complete block
      design to determine the effects of feeding Ca and Na salts (1:1, wt/wt) of
      propionate and Ca salts of long-chain fatty acids (LCFA) on transition cow
      performance. All cows were fed the same basal diet once daily for ad libitum
      intake. Treatments (g/d) were 320 cornstarch (CS) as a control, 120 propionate
      (PRO), 120 propionate and 93 LCFA (PF1), and 178 propionate and 154 LCFA (PF2).
      Treatments were hand-mixed into the upper one-third of the TMR from 2 wk pre-
      through 3 wk postpartum. Intakes were recorded from 21 d pre- through 21 d
      postpartum. Energy density and crude protein were 1.54 and 1.65 Mcal/kg and 14.4
      and 18.8% for pre- and postpartum diets, respectively. All cows received a common
      diet from 22 to 70 days in milk (DIM). Milk composition was analyzed on d 7, 14,
      and 21. Blood was sampled at 14, 7, and 2 d prepartum and 2, 7, 14, and 21 DIM.
      Pre- and postpartal dry matter intake (DMI) averaged 11.9 and 16.4 kg/d,
      respectively, and did not differ among treatments. A diet x week interaction for
      postpartal DMI was observed as cows fed PF2 consumed 2 kg/d less DM during wk 2
      relative to other treatments. Milk yields from 22 to 70 DIM were 48.8, 48.5,
      47.8, and 51.3 kg/d for CS, PRO, PF1, and PF2, respectively, and were not
      significantly affected by treatments. Milk true protein (3.32 vs. 3.16%) was
      increased and MUN (12.5 vs. 14.4 mg/dL) was decreased for CS relative to other
      treatments. Milk fat yield from cows fed PRO tended to be greater than those fed
      PF1 (1.58 vs. 1.29 kg/d). Plasma glucose, insulin, and beta-hydroxybutyrate were
      not affected by treatments. The PF2 treatment tended to decrease NEFA in plasma
      relative to PF1 over all times measured (492 and 670 muEq/L) and significantly
      decreased plasma NEFA relative to those fed PF1 postpartum (623 and 875 muEq/L).
      Relative to PF1, feeding propionate and LCFA at the higher level in this
      experiment improved energy balance postpartum as evidenced by decreased
      concentrations of plasma NEFA.

PMID- 15738234
TI  - Effect of fibrolytic enzymes on the fermentation characteristics, aerobic
      stability, and digestibility of bermudagrass silage.
AB  - The aim of this study was to determine if the nutritive value and aerobic
      stability of bermudagrass (Cynodon dactylon) silage could be improved by addition
      of proprietary, exogenous cellulase/hemicellulase enzyme preparations at
      ensiling. A 5-wk regrowth of Tifton 85 bermudagrass was conserved without
      treatment (control) or after treatment with exogenous fibrolytic enzymes
      including Promote NET (Pr), Biocellulase X-20 (X20), Biocellulase A-20 (A20), and
      Enzyme CT. The respective enzymes were applied at half the recommended rate, the
      recommended rate, or twice the recommended rate corresponding to 0.65, 1.3, and
      2.6 g/kg of DM, 7.3, 14.5, and 29 mg/kg of DM, at 7.3, 14.4, and 29 mg/kg of DM,
      and 89, 178, and 356 mg/kg of DM, for Pr, X20, A20, and CT, respectively. The
      enzymes were sprayed on the bermudagrass at ensiling (not added at feeding as
      suggested by the manufacturers) to test the objectives of the study. Six 1-kg
      replicates of chopped (5 cm) forage were ensiled for 145 d in 2.8-L mini silos.
      Three silos per treatment were used for chemical analysis and 3 for aerobic
      stability monitoring. The silage juice was analyzed for organic acids, pH, water
      soluble carbohydrates (WSC), ammonia-N, and soluble N. Freeze-dried samples were
      analyzed for crude protein (CP), neutral detergent fiber (NDF), and acid
      detergent fiber (ADF). In vitro digestibility of DM (IVDMD), NDF (IVNDFD), and
      ADF (IVADFD) were determined after digesting the silages in buffered rumen fluid
      for 6 or 48 h in 2 ANKOM(II) Daisy Incubators. Compared with the other silages,
      those treated with Pr had lower DM losses, and lower pH and ammonia-N
      concentration than control silages. Residual WSC concentration was greater in Pr-
      and CT-treated silages than in control silages and greater in Pr-treated silages
      than CT-treated silages. Compared with control silages, NDF concentration was
      lower in silages treated with Pr, X20, and CT, and ADF concentration was lower in
      silages treated with Pr, X20, and A20. Nevertheless, Pr-treated silages contained
      lower ADF and NDF concentrations than silages treated with the other enzymes.
      Enzyme-treated silages contained less acetic acid than control silages, and Pr
      treated silages had the lowest concentrations of acetic acid. Aerobic stability
      was increased by enzyme treatment but microbial counts were not affected. The 6-h
      IVDMD was increased by treatment with Pr and A20, however only Pr increased the
      IVDMD and IVNDFD at 48 h. The 48-h IVADFD was also increased by treatment with
      Pr, CT, and A20. These results show that when applied at ensiling, certain
      fibrolytic enzymes (particularly Promote) can improve the digestibility,
      fermentation, and aerobic stability of bermudagrass silage.

PMID- 15738235
TI  - Reducing dry period length to simplify feeding transition cows: milk production,
      energy balance, and metabolic profiles.
AB  - Sixty-five Holstein cows were used to evaluate management schemes involving
      altered dry period (DP) lengths on subsequent milk production, energy balance
      (EB), and metabolic variables. Cows were assigned to one of 3 treatments:
      traditional 56-d DP (fed a low-energy diet from -56 to -29 d and a moderate
      energy diet from -28 d to parturition; T), 28-d DP (continuously fed a high
      energy diet; S), and no planned DP (continuously fed a high energy diet; N).
      Prepartum DM intake (DMI), measured from 56 d prepartum through parturition, was
      lower for cows on the T treatment than for cows on the S treatment and was higher
      for cows on the N treatment than for cows on the S treatment. There were no
      differences in prepartum plasma glucose, and beta-hydroxybutryric acid; there was
      a treatment by time interaction for prepartum plasma nonesterified fatty acid
      (NEFA). There was no difference in prepartum liver triglyceride (TG); postpartum
      liver TG was decreased for cows on the N treatment compared with cows on the S
      treatment, but was similar for cows on the T and S treatments. Postpartum NEFA
      was similar between cows on the T and S treatments, but was greater for cows on
      the S treatment than for cows on the N treatment. Postpartum glucose was greater
      for cows on the N treatment compared with cows on the S treatment and tended to
      be greater for cows on the S treatment than for cows on the T treatment. There
      was no difference in postpartum solids-corrected milk (SCM) production or DMI by
      cows on the T vs. S treatment. However, there was a tendency toward lower
      postpartum SCM production by cows on the N vs. S treatment and a tendency for
      greater postpartum DMI by cows on the N vs. S treatment. Postpartum EB was
      greater for cows on the S vs. T treatment and the N vs. S treatment. In general,
      T and S management schemes had similar effects on DMI, SCM, and metabolic
      variables in the first 70 d of the subsequent lactation. Eliminating the DP
      improved energy and metabolic status.

PMID- 15738236
TI  - Nutrient digestibility of diets with different fiber to starch ratios when fed to
      lactating dairy cows.
AB  - The objective of this experiment was to determine whether increasing the dietary
      neutral detergent fiber (NDF):starch ratio affected NDF digestibility when diets
      were formulated to have equal in situ NDF digestibility. Six lactating Holstein
      cows were fed 1 of 3 diets in a replicated 3 x 3 Latin square. All diets had
      41.5% of the dry matter (DM) as corn silage but the concentration of corn grain
      varied from 23.3 to 34.8% and the NDF:starch ratios were 0.74, 0.95, and 1.27. As
      corn grain increased, the concentration of a mixture of 54% soyhulls and 46%
      cottonseed hulls decreased. The soyhull:cottonseed hull mixture had the same in
      situ NDF digestibility as the corn silage. All diets had 18% forage NDF but
      starch concentration varied from 25.4 to 33.3% and NDF varied from 24.7 to 32.2%.
      Intake tended to increase as the NDF:starch ratio increased. Total tract
      digestibility (measured by total collection of feces and urine) of dry matter and
      energy decreased linearly as the NDF:starch ratio increased, but NDF
      digestibility was not affected by treatment. Retention of N increased linearly as
      the NDF:starch ratio increased. As dietary NDF:starch ratio increased, ruminal pH
      was not affected, but the concentration of total volatile fatty acids (VFA)
      decreased and the VFA profile was altered by diet. Consistent with the observed
      changes in ruminal VFA, milk fat percentage increased with increasing dietary
      NDF:starch. Intake of digestible energy and output of energy in milk and body
      weight change was not affected by treatment.

PMID- 15738237
TI  - Goat milk feeding causes an increase in biliary secretion of cholesterol and a
      decrease in plasma cholesterol levels in rats.
AB  - The hypocholesterolemic effect of goat milk with respect to cow milk observed in
      a previous study led us to examine the influence of goat and cow milk in the diet
      on certain aspects of biliary physiology in normal rats. The fat content in all
      diets was 10% but the lipid quality was varied: the standard diet was based on
      virgin olive oil, and the other 2 diets included fat obtained from lyophilized
      cow milk and goat milk. We characterized the bile secretion, including biliary
      phospholipid, cholesterol, and bile acid outputs, the interrelation between bile
      acids and bile lipids, and the lithogenic index. The consumption of goat milk in
      the diet, compared with that of cow milk, caused an increase in the biliary
      secretion of cholesterol together with a decrease in plasma cholesterol
      concentration, whereas values for bile phospholipids, biliary acid
      concentrations, and the lithogenic index remained normal. Moreover, consumption
      of this type of milk decreased plasma triglyceride concentration and therefore
      had a positive effect, similar to that of olive oil (standard diet), on the lipid
      metabolism; hence, it may be recommended for consumption by the general
      population.

PMID- 15738238
TI  - Use of odd and branched-chain fatty acids in rumen contents and milk as a
      potential microbial marker.
AB  - The objectives of this study were: 1) to determine if a correlation exists
      between rumen odd and branched-chain fatty acids (OBCFA, i.e., C(15:0), iso
      C(15:0), anteiso C(15:0), C(17:0), iso C(17:0), anteiso C(17:0), and C(17:1)),
      uracil, and purine bases (PB), 2) to evaluate the potential of milk OBCFA
      secretion to predict duodenal flow of microbial protein in lactating cows, 3) to
      evaluate the accuracy of the latter prediction equations using an independent
      data set, and 4) to determine whether these predictions were more accurate than
      predictions based on dry matter intake (DMI) and dietary characteristics. In the
      first experiment, 4 lactating dairy cows arranged in a 4 x 4 Latin square were
      offered diets based on grass silages of different botanical composition and a
      standard concentrate. The relationship between rumen pool size of OBCFA and
      microbial matter was investigated. Rumen pool size of microbial matter (g),
      determined 4, 12, and 17 h after feeding, using uracil and PB as microbial
      markers, was closely related to OBCFA (g) [r(2) = 0.716, root mean square error
      (RMSE) = 4.45]. To correct for differences in marker concentrations among strains
      of rumen microbes, C(17:0) was included in the regression equations, resulting in
      an increased predictive power (r(2) = 0.780, RMSE = 3.92). The relationship
      between microbial flow to the duodenum and milk OBCFA yield was evaluated in a
      second experiment with lactating dairy cows offered diets based on grass silage
      and concentrates differing in starch source. Similar to observations in the
      rumen, milk OBCFA yield was closely related to microbial flow to the duodenum
      (RMSE = 4.28), but predictive power of equations did not increase when straight
      chain C(17)-fatty acids were included in the regression equations (RMSE = 4.92).
      Evaluation of the current prediction equations with 3 independent datasets
      resulted in a root mean square prediction error of 20.5 and 13.4% of the observed
      mean for equations based on milk secretion of total OBCFA and straight-chain
      C(17)-fatty acids, respectively. Comparison of the accuracy of the latter
      equations with 2 previously published equations based on DMI and dietary
      characteristics suggest the former to be more accurate. This first evaluation
      suggests that milk OBCFA could be used as a marker for duodenal flow of microbial
      matter, especially when accurate measurements of DMI are not available.

PMID- 15738239
TI  - Effect of water addition on selective consumption (sorting) of dry diets by dairy
      cattle.
AB  - The objective of this study was to determine whether adding water to a dry diet
      would reduce sorting and improve cow performance. Eighteen multiparous lactating
      Holstein cows were used in a cross-over design with 21-d periods. Treatments had
      the same dietary composition and differed only by adding water (WET) or not
      (DRY). Diets consisted of 10% alfalfa silage, 30% hay (approximately 80% grass
      and 20% alfalfa), and 60% concentrate [dry matter (DM) basis]. Dietary DM was
      80.8% for DRY and 64.4% for WET. Both diets contained 16.9% crude protein and
      24.3% neutral detergent fiber. Particle size was determined using the Wisconsin
      Particle Size Separator on the as-fed diets. The separator has five square-hole
      screens (Y(1) to Y(5)) with diagonal openings of 26.9 mm for Y(1), 18 mm for
      Y(2), 8.98 mm for Y(3), 5.61 mm for Y(4), and 1.65 mm for Y(5), and one pan.
      Sorting was calculated on a 60 degrees C DM basis (60DM). Predicted intake of
      Y(i) was calculated as the product of 60DM intake (60DMI) and the 60DM fraction
      of Y(i) in the total mixed ration for that screen. For DRY and WET, actual 60DMI
      by screen expressed as a percentage of predicted intake was 61.4% vs. 75.2% for
      Y(1), 83.8% vs. 98.6% for Y(2), 85.6% vs. 90.8% for Y(3), 95.2% vs. 96.0% for
      Y(4), 100.1% vs. 101.9% for Y(5), and 105.9% vs. 102.9% for pan, respectively.
      Adding water did not affect total DM intake (28.3 kg/d) or milk production (41.3
      kg/d). Neutral detergent fiber intake was 6.42 kg/d for WET and 6.15 kg/d for
      DRY. Milk fat percentage tended to be higher (3.41% vs. 3.31%) when cows consumed
      WET vs. DRY. No differences in ruminal pH, NH(3), and volatile fatty acids were
      observed. Cows sorted against long particles in favor of shorter particles on
      both diets. Adding water to dry diets reduced sorting and tended to increase
      neutral detergent fiber intake and milk fat percentage.

PMID- 15738240
TI  - Effects of feeding vitamin A and lactoferrin on epithelium of lymphoid tissues of
      intestine of neonatal calves.
AB  - Circulating levels of vitamin A (retinol) and lactoferrin (Lf) are low in calves
      at birth. Bovine colostrum contains relatively high amounts of vitamin A and Lf,
      and both substances are intestinally absorbed by neonatal calves. There is
      evidence that these compounds interact with insulin-like growth factor binding
      proteins and thus influence the status and effects of insulin-like growth factor.
      The hypothesis was therefore tested that vitamin A and Lf influence epithelial
      growth, development, and absorptive capacity of the small and large intestine and
      modulate intestinal immune tissues (Peyer's patches; PP). Four groups of calves
      (n = 7 per group) were fed a milk-based formula with or without vitamin A and
      (or) Lf. Group F received formula (F) only; group F(A) was fed F supplemented
      with vitamin A; group F(L) was fed F supplemented with Lf, and group F(AL)
      received F plus vitamin A plus Lf. An additional group of calves (group C; n = 7)
      served as positive control and was fed colostrum (C) from pooled milk obtained on
      d 1, 2, and 3 of lactation. Amounts of nutritive components in formula and
      colostrum were similar. Blood samples were taken to measure vitamin A and Lf, and
      plasma xylose (added on d 4 to feeds) was measured postprandially for 8 h as a
      marker of intestinal absorptive capacity. Plasma vitamin A was low at birth and
      further decreased in groups F and F(L), but increased in groups F(A), F(AL), and
      C. Plasma Lf was low at birth and transiently increased up to 4 h after the first
      meal in group C. Xylose absorption was higher in group C than in other groups.
      Incorporation of 5-bromo-2'-deoxyuridine into DNA (as a measure of cell
      proliferation rate) was enhanced in intestinal crypts in groups F and F(L) at all
      intestinal sites. Ileum villus heights of groups F and F(L) were smaller than of
      groups F(A) and F(AL). Villus height to crypt depth ratios were smaller in F-fed
      groups (especially in groups F and F(L)) than in C-fed calves in the duodenum and
      jejunum. Incorporation of 5-bromo-2'-deoxyuridine into colon crypt cells of group
      F was greater than in groups F(L) and F(A). Sizes of follicles of PP in the ileum
      were greater in group F(A) than in group F. In the ileum, vitamin A and Lf tended
      to interact with PP size. In conclusion, feed supplementation of vitamin A and Lf
      influenced growth of the ileum and colon. Interactions were observed between
      vitamin A and Lf on epithelial cell maturation, villus growth, and size of
      follicles in PP of neonatal calves.

PMID- 15738241
TI  - Hematological, metabolic, and endocrine effects of feeding vitamin A and
      lactoferrin in neonatal calves.
AB  - There are reports of important interactions among vitamin A, lactoferrin (Lf),
      and components of the insulin-like growth factor (IGF) system. Newborn calves are
      deficient in vitamin A and have a low Lf status. Colostrum contains vitamin A,
      Lf, and members of the IGF system, including IGF binding proteins (IGFBP), and
      these compounds may exert mutual interactions in neonatal calves. Effects of
      feeding different amounts of vitamin A and Lf on hematological, metabolic, and
      endocrine traits during the first 5 d of life were studied in neonatal calves.
      Calves were fed a milk-based formula without (F) or with added vitamin A [F(A);
      351, 402, 490, and 490 micromol/kg dry matter (DM) on d 1, 2, 3, and 4,
      respectively], Lf (F(L); 3850, 1990, 660, and 660 mg/kg DM on d 1, 2, 3, and 4,
      respectively), or vitamin A + Lf (F(AL)) and colostrum (C). Blood samples were
      taken preprandially on d 1 to 5 and postprandially on d 1, 2, and 4 for the study
      of hematological, metabolic, and endocrine traits. As intestinal absorption of Lf
      in formula-fed calves was obviously lower than in colostrum-fed calves, Lf
      supplementation did not influence the metabolic and endocrine status. Plasma
      vitamin A concentrations increased from d 1 to 5 in F(A), F(AL), and C, but
      remained low in F and F(L). Addition of vitamin A to F affected concentrations of
      vitamin A from d 2 to 5; hemoglobin and triglycerides on d 3; and tended to
      influence IGFBP-3 levels on d 5. On d 1, preprandial insulin concentrations in F
      and F(L) were higher than those in F(A) and F(AL) and growth hormone
      concentrations on d 3 in F(A) were higher than in F(AL). In C, plasma Lf
      concentrations increased on d 1 and then decreased until d 5, whereas plasma urea
      and IGF-I concentrations remained stable. Compared with F-fed calves, C-fed
      calves had higher plasma concentrations of Lf from d 1 to 4, higher
      concentrations of vitamin A on d 5, higher concentrations of total protein from d
      2 to 5, higher concentrations of triglycerides on d 3 and 4, and higher
      concentrations of IGF-I on d 4 and 5, but lower urea concentrations on d 4 and 5
      and lower basal growth hormone concentrations than in F, F(L), and F(A). In
      conclusion, metabolite and hormone concentrations were influenced by differences
      in feeding. Addition of vitamin A influenced concentrations of vitamin A,
      hemoglobin, and triglycerides and tended to affect IGFBP-3 levels. Lactoferrin
      and vitamin A did not interact with respect to the IGF-I and IGFBP-3 status.

PMID- 15738243
TI  - Effects of physically effective fiber on digestion and milk production by dairy
      cows fed diets based on corn silage.
AB  - Effects of physically effective (pe) neutral detergent fiber (NDF) content of
      dairy cow diets on nutrient intakes, site and extent of digestion, microbial
      protein synthesis and milk production were evaluated in a double 3 x 3 Latin
      square design using 6 lactating dairy cows with ruminal and duodenal cannulas.
      During each of 3 periods, cows were offered 1 of 3 diets that were chemically
      similar but varied in peNDF content (high, medium, and low) by altering corn
      silage particle length. The peNDF contents were determined using the Penn State
      Particle Separator and were 11.5, 10.3, and 8.9%, for the high, medium, and low
      diets, respectively, and the physical effectiveness factors for the long, medium,
      and fine silages were 84.1, 72.6, and 67.2%, respectively. Increased forage
      particle length increased intake of peNDF but did not affect intakes of nutrients
      including dry matter, NDF, starch, and nitrogen. Except for starch, apparent
      digestibilities of nutrients in the total tract were linearly increased with
      increasing dietary peNDF. Fiber digestion was affected by dietary peNDF to a
      greater extent than were the other nutrients. However, increased digestibility
      due to increased dietary peNDF did not significantly improve milk production or
      milk composition. Increased dietary peNDF also increased numerically rumen
      microbial protein synthesis due to increased amount of organic matter fermented
      in the rumen. These results indicate that increasing the peNDF content of a corn
      silage based diet improves digestibility, especially digestibility of fiber, in
      the total tract. Dietary particle size, expressed as peNDF, is positively
      associated with nutrient digestibility when level of peNDF in the diet is low.

PMID- 15738242
TI  - Dietary supplements of two doses of calcium salts of conjugated linoleic acid
      during the transition period and early lactation.
AB  - Reduction of milk fat secretion by the use of conjugated linoleic acid (CLA)
      supplements may alleviate energy demands during early lactation. The objective of
      the present study was to evaluate lactational performance, net energy balance,
      and reproductive response of dairy cows supplemented with 2 doses of CLA from 2
      wk before predicted calving until 9 wk postpartum. Holstein cows (n = 48) were
      divided into 3 treatment groups: 1) control, 2) low dose CLA treatment (CLA-1),
      and 3) high dose CLA treatment (CLA-2). Supplements for all treatments provided
      230 g/d of fat; the control group received Ca salts of palm fatty acid distillate
      and the CLA groups received a mixture of Ca salts of CLA isomers and Ca salts of
      palm fatty acid distillate (31.6 and 63.2 g/d of CLA isomers for CLA-1 and CLA-2,
      respectively). Supplementation with CLA resulted in an 11 and 21% decrease in
      milk fat yield for CLA-1 and CLA-2, respectively. Milk production and secretion
      of other milk components did not differ among treatments. Milk energy output was
      significantly reduced with CLA-2, but net energy balance, body weight, and body
      condition scores were unaffected. Treatment had no effect on hepatic triglyceride
      concentration or plasma glucose and insulin, but nonesterified fatty acids tended
      to be lower for CLA-1. There were no consistent dose-related effects on
      reproduction variables, and no adverse effects were observed during the treatment
      or posttreatment period. Supplemental CLA was effective in reducing milk fat
      content, but it did not have a significant effect on milk yield or net energy
      balance.

PMID- 15738244
TI  - Effect of rumen-degradable protein balance and forage type on bulk milk urea
      concentration and emission of ammonia from dairy cow houses.
AB  - As the Dutch government and dairy farming sector have given priority to reducing
      ammonia emission, the effect of diet on the ammonia emission from dairy cow barns
      was studied. In addition, the usefulness of milk urea content as an indicator of
      emission reduction was evaluated. An experiment was carried out with a herd of 55
      to 57 Holstein-Friesian dairy cows housed in a naturally ventilated barn with
      cubicles and a slatted floor. The experiment was designed as a 3 x 3 factorial
      trial and repeated 3 times. During the experiment, cows were confined to the barn
      (no grazing) and were fed ensiled forages and additional concentrates. The
      default forage was grass silage. The nutritional experimental factors were: (1)
      rumen-degradable protein balance of the ration for lactating cows with 3 levels
      (0, 500, and 1000 g/cow per d), and (2) proportion of corn silage in the forage
      ration for lactating cows with 3 levels (0, 50, and 100%) of forage dry matter
      intake. Several series of dynamic regression models were fitted. One of these
      models explained emission of ammonia by the nutritional factors and the
      temperature; another model explained ammonia emission by the bulk milk urea
      content and the temperature. The ammonia emission from the barn increased when
      levels of rumen-degradable protein balance increased. Furthermore, at a given
      level of rumen-degradable protein balance, the emission of ammonia correlated
      positively with the corn silage content in the forage ration. However, this
      correlation was not causal, but was the result of interaction between corn silage
      proportion and intake of ileal digestible protein. The bulk milk urea content and
      the temperature correlated strongly with the ammonia emission from the barn; the
      selected model accounted for 76% of the variance in emission. It was concluded
      that the emission of ammonia from naturally ventilated dairy cow barns was
      strongly influenced by diet. The emission can be reduced approximately 50% by
      reducing the rumen-degradable protein balance of the ration from 1000 to 0 g/cow
      per d. The milk urea content is a good indicator of emission reduction.

PMID- 15738245
TI  - Improving intestinal amino acid supply of pre- and postpartum dairy cows with
      rumen-protected methionine and lysine.
AB  - Eighty-four Holstein cows were assigned to a randomized block experiment to
      determine effects of supplementing pre- and postpartum diets containing highLys
      protein supplements with rumen-protected Met and Lys. Before parturition, cows
      received a basal diet with 1) no rumen-protected amino acids (AA), 2) 10.5 g/d of
      Met from rumen-protected Met, or 3) 10.2 g/d of Met and 16.0 g/d of Lys from
      rumen-protected Met plus Lys. After parturition, cows continued to receive AA
      treatments but switched to diets balanced for 16.0 or 18.5% crude protein (CP).
      Diets were corn-based; supplemental protein was provided by soybean products and
      blood meal. Cows received treatments through d 105 of lactation. Compared with
      basal and Met-supplemented diets, Met + Lys supplementation increased yield of
      energy-corrected milk, fat, and protein, and tended to increase production of
      3.5% fat-corrected milk. Significant CP x AA interactions were observed only for
      milk protein and fat content. Supplementation of the 16% CP diet with Met and Met
      + Lys had no effect on milk true protein and fat content. However, Met and Met +
      Lys supplementation of the 18.5% CP diet increased milk protein content by 0.21
      and 0.14 percentage units, respectively, and Met supplementation increased fat
      content by 0.26 percentage units. Results of this study indicate that early
      lactation cows fed corn-based diets are responsive to increased intestinal
      supplies of Lys and Met and that the responses depend on dietary CP
      concentration, supply of metabolizable protein, and intestinal digestibility of
      the rumen-undegradable fraction of supplemental proteins.

PMID- 15738246
TI  - Effect of body fatness and glucogenic supplement on lipid and protein
      mobilization and plasma leptin in dairy cows.
AB  - Twenty-four multiparous Ayrshire cows were used in an experiment to test the
      effect of body fatness and glucogenic supplement, fed during the transition
      period, on lipid and protein mobilization and plasma hormone concentrations.
      Eight weeks before their expected calving date, the cows were divided into blocks
      of 4. Two cows with the highest body condition score within each block were then
      allocated to a test (T) group and the other 2 cows to a control (C) group. To
      scale up the differences between fatter and thinner cows, the estimated energy
      allowance was 40% higher in group T than in group C between d 56 and 21
      prepartum. For the final 3 wk before calving, all the cows were fed according to
      energy recommendations for pregnant cows. Within C and T groups and blocks, cows
      were randomly assigned into groups with (G1) or without (G0) glucogenic
      supplement. Division to G0 and G1 groups was made 2 wk before the expected
      calving and continued for 56 d postpartum. After calving, all the cows received
      grass silage ad libitum and a common daily concentrate allowance. No significant
      differences were detected in feed intake and milk yield between C and T. The T
      groups showed an earlier rise of nonesterified fatty acids as calving approached
      and had higher plasma nonesterified fatty acids during the final week of
      pregnancy and lactation wk 1 to 3. At the same time, adipose tissue samples from
      fatter cows tended to show higher in vitro lipolytic responses to added
      norepinephrine, as monitored by glycerol release. Protein mobilization was
      elevated during the final week of pregnancy and tended to be more increased in
      fatter cows. Glucogenic supplement did not decrease lipid or protein
      mobilization. Fatter cows had higher plasma leptin concentration prepartum,
      showed a more pronounced decrease in leptin concentration near calving, and had
      higher plasma leptin concentration after calving. In conclusion, fatter cows
      initiated more extensive mobilization of body fat before calving and this
      continued during the first lactation weeks. Plasma leptin concentration in early
      lactation cows was associated with body fatness and not with estimated energy
      balance.

PMID- 15738247
TI  - Endogenous production of n-3 and n-6 fatty acids in mammalian cells.
AB  - Polyunsaturated fatty acids (PUFA) are important components of mammalian diets,
      and the beneficial effects of n-3 PUFA on human development and cardiovascular
      health have been well documented. Caenorhabditis elegans is one of the few
      animals known to be able to produce linoleic (LA, 18:2n-6) and alpha-linolenic
      (ALA, 18:3n-3) essential fatty acids. These essential PUFA are generated by the
      action of desaturases that successively direct the conversion of monounsaturated
      fatty acids (MUFA) to PUFA. The cDNA coding sequences of the C. elegans Delta(12)
      and n-3 fatty acid desaturases were each placed under the control of separate
      constitutive eukaryotic promoters and simultaneously introduced into HC11 mouse
      mammary epithelial cells by adenoviral transduction. Phospholipids from
      transduced cells showed a significant decrease in the ratios of both MUFA:PUFA
      and n-6:n-3 fatty acids relative to control cultures. The fatty acid profile of
      transduced cellular phospholipids revealed significant decreases in MUFA and
      arachidonic acid (20:4n-6), and increases in LA, ALA, and eicosapentaenoic acid
      (20:5n-3). The fatty acid composition of triacylglycerols derived from transduced
      cells was similarly, but less dramatically, affected. These results demonstrate
      the functionality of C. elegans fatty acid desaturase enzymes in mammalian cells.
      Expression of these desaturases in livestock might act to counterbalance the
      saturating effect that rumen microbial biohydrogenation has on the fatty acid
      profile of ruminant products, and allow for the development of novel, land-based
      dietary sources of n-3 PUFA.

PMID- 15738248
TI  - Characterization of days dry for United States Holsteins.
AB  - This research characterized days dry (DD) for modern US Holsteins. This included
      investigation of factors influencing DD, summarizing variation in herd means as
      well as within-herd variation, and estimation of parameters related to DD. Data
      consisted of records initiated before 2003 from cows first calving after 1996. A
      total of 459,075 records from 295,067 cows in 3527 herds were included. The
      overall mean DD was 60.5 d, and standard deviation among herd means was 5.8 d.
      Approximately 91% of all herds had mean DD between 50 and 70 d. There were 41
      herds that had mean DD of < or =45 d and 2 herds with mean DD of < or =30 d. Some
      herds (125) had unusually long mean DD (exceeding 71 d). Variation across regions
      of the United States was minimal, although southwestern herds did show somewhat
      longer DD than other regions. Days open (DO) accounted for the most variation in
      DD with longer DO leading to longer dry periods. Heritability of DD was 7% and
      repeatability 12%. Error correlations indicated that longer dry periods benefit
      both milk yield and somatic cell score in the subsequent lactation. Genetic and
      permanent environmental correlations were large, which indicated that 1) bias
      would result if genetic evaluations for milk yield included an adjustment for DD,
      and 2) correction for cow effects is warranted in estimation of DD effects on
      performance. The relationship between DD and DO is due primarily to permanent cow
      effects. Improved fertility will enhance the feasibility of shortened dry
      periods.

PMID- 15738249
TI  - Changing definition of productive life in US Holsteins: effect on genetic
      correlations.
AB  - Data included 392,800 records for cows born between 1995 and 1997. Traits
      analyzed were milk, fat, and protein yields, somatic cell score, days open (DO),
      18 linear type traits, final score, and several measures of longevity. Productive
      life (PL) was defined as the total number of days in milk up to 84 mo of age with
      a restriction of 305, 500, or 999 d per lactation (PL(305), PL(500), or PL(999),
      respectively). Herd life was defined as the total number of days from the first
      calving date to the last (culling) date. A multiple-trait sire model including
      the effects of registration status, herd-year, age group, month of calving and
      stage of lactation, sire, and residual was used for parameter estimation. The
      average duration of the first lactation was 365 d for survivors and 386 d for
      culled cows. Lactation lengths for the survivors in the next 3 parities all
      exceeded 330 d. Heritability estimates of between 0.08 and 0.10 were obtained for
      all definitions of longevity. As maximum recordable PL was increased from 305 to
      999 d per lactation, the genetic correlations with milk production increased
      (from -0.11 to +0.14) and with DO decreased (-0.62 to -0.27). Formulas for an
      indirect prediction of PL from correlated traits were developed. As maximum PL
      per lactation was increased, little change in the weights used to predict the
      various measures of PL, with the exception of DO was found. As the currently used
      value of PL(305) does not properly account for the longer lactation lengths that
      are routinely occurring with today's cows, PL with longer lactations may be
      preferable in routine evaluation.

PMID- 15738250
TI  - Estimation of genetic parameters for milk fat depression in dairy cattle.
AB  - The objective of this study was to apply reaction norm models to milk recording
      data to investigate genetic variation in and environmental sensitivity of
      susceptibility to milk fat depression (MFD). Data comprised 556,276 test-day
      records of 80,493 heifers in 1043 herds. Breeding values and genetic variances
      for fat percentage and fat yield were estimated by applying random regression
      models to average herd-test-day fat percentage. Genetic and permanent
      environmental correlations between fat yield expressed in different environments
      ranged, respectively, from 0.83 to 1.00 and from 0.29 to 1.00. Genetic and
      permanent environmental correlations between fat percentage expressed in
      different environments ranged, respectively, from 0.87 to 1.00 and from -0.05 to
      0.99. Two traits were defined for MFD. The first trait reflected variation of
      milk fat percentage of animals within lactation after correction for year-season,
      herd-test-day, age-at-calving, and stage-of-lactation. This trait had an
      estimated heritability of about 5% and a genetic correlation between the fifth
      and 95th percentile of the data of 0.50. The second trait reflected the deviation
      of an animal's fat percentage on a test-day from its expected fat percentage
      based on fat percentage on the first test-day. This trait had an estimated
      heritability of about 4% and a genetic correlation between the fifth and 95th
      percentile of the data of 0.43. The correlation between estimated breeding values
      of sires for the 2 MFD traits was -0.3. Our results suggest that genetic
      variation in susceptibility to MFD is present and that selection for reduced
      susceptibility to MFD is possible.

PMID- 15738251
TI  - Detection of different shapes of lactation curve for milk yield in dairy cattle
      by empirical mathematical models.
AB  - The study of relationships between mathematical properties of functions used to
      model lactation curves is usually limited to the evaluation of the goodness of
      fit. Problems related to the existence of different lactation curve shapes are
      usually neglected or solved drastically by considering shapes markedly different
      from the standard as biologically atypical. A deeper investigation could yield
      useful indications for developing technical tools aimed at modifying the
      lactation curve in a desirable fashion. Relationships between mathematical
      properties and lactation curve shapes were analyzed by fitting several common
      functions (Wood incomplete gamma, Wilmink's exponential, Ali and Schaeffer's
      polynomial regression, and fifth-order Legendre polynomials) to 229,518 test-day
      records belonging to 27,837 lactations of Italian Simmental cows. Among the best
      fits (adjusted r(2) higher than 0.75), the 3-parameter models (Wood and Wilmink)
      were able to detect 2 main groups of curve shape: standard and atypical. Five
      parameter models (Ali and Schaeffer function and the Legendre polynomials) were
      able to recognize a larger number of curve shapes. The higher flexibility of 5
      parameter models was accompanied by increased sensitivity to local random
      variation as evidenced by the bias in estimated test-day yields at the beginning
      and end of lactation (border effect). Meaning of parameters, range of their
      values and of their (co) variances are clearly different among groups of curves.
      Our results suggest that analysis based on comparisons between parameter values
      and (co)variances should be done carefully. Comparisons among parameter values
      and (co)variances could yield more robust, reliable, and easy to interpret
      results if performed within groups based on curve shape.

PMID- 15738252
TI  - Genetic evaluation of dairy sires for milking duration using electronically
      recorded milking times of their daughters.
AB  - The potential of using electronically recorded data from on-farm milking parlor
      and herd management software programs for genetic evaluation of dairy sires for
      milking duration of their daughters was assessed in the present study. Single
      measurements of milking duration were collected weekly from 29 herds between June
      1, 2003 and April 1, 2004. These included 73,547 observations corresponding to
      10,152 Holstein cows from 1551 sires. Average milking duration for a single
      milking in our data set was 4.5 min. Estimated heritability of milking duration
      was 0.17, and predicted transmitting abilities (PTA) of individual sires ranged
      from -0.48 min for sires with the fastest milking daughters to 0.59 min for sires
      with the slowest milking daughters. The correlation between PTA for milking
      duration and PTA for somatic cell score (SCS) was -0.15, indicating that sires
      whose daughters milk most quickly also tend to transmit higher SCS to their
      progeny. Correlations between PTA milking duration and PTA for teat placement and
      teat length were -0.14 and 0.20, respectively, indicating that sires that
      transmit wide teat placement and long teats tend to have daughters that milk
      slowly. Based on the results presented herein, it appears that genetic selection
      based on objective, electronically recorded milking times is possible. This
      approach would greatly improve the quality and efficiency of data collection
      relative to conventional evaluations of milking speed, which are based on farmer
      surveys. The number of herds currently equipped to routinely capture milking
      times is limited, but this number is increasing very rapidly. Future research
      should focus on refinement of data reporting and validation systems, as well as
      estimation of the economic value of milking duration. This trait may have an
      intermediate optimum, because cows that milk too slowly will disrupt parlor flow
      and reduce milking efficiency, but cows that milk too quickly may be at greater
      risk for mastitis.

PMID- 15738254
TI  - Association of the protease inhibitor gene with production traits in Holstein
      dairy cattle.
AB  - Positional, comparative candidate gene analysis and previous quantitative trait
      loci linkage mapping results were used to search for candidate genes affecting
      milk production and reproduction traits in dairy cattle. The protease inhibitor
      (PI) gene was chosen for examination, and 5 single nucleotide polymorphisms were
      detected in coding regions of the gene by direct sequencing of reverse
      transcription-polymerase chain reaction products from a wide range of cattle
      tissues. A total of 6 different intragenic haplotypes were identified in North
      American Holstein population, and these were examined for associations with milk
      production traits in 24 half-sib families comprising 1007 sons utilizing a
      granddaughter design. One common haplotype was associated with increased milk and
      fat yields, increased productive life, and decreased somatic cell score. Another
      common haplotype was associated with decreased productive life and increased
      somatic cell score. One rare haplotype was associated with decreased milk, fat,
      and protein yields and increased milk protein percentage; another rare haplotype
      was associated with decreased milk yield, increased protein percentage, and
      decreased productive life. The observation that the PI gene is associated with
      analogous traits in humans demonstrates the effectiveness of the positional
      comparative candidate gene analysis that utilizes information about genes present
      in chromosomal regions with conserved synteny in other species.

PMID- 15738253
TI  - Genetic basis and risk factors for infectious and noninfectious diseases in US
      Holsteins. I. Estimation of genetic parameters for single diseases and general
      health.
AB  - Health data collected from 1996 to 1999 from 177 herds in Minnesota and Wisconsin
      were analyzed to establish genetic basis for infectious and noninfectious
      diseases. Three types of health traits were targeted. First, available infectious
      conditions were used to identify animals that are superior in their general
      immunity (including innate immunity) for infectious diseases. Generalized
      immunity may be thought of as a combination of immune responses to a variety of
      immune system challenges. Second, single infectious and noninfectious diseases
      were analyzed separately. Third, infectious reproductive diseases as one category
      of related conditions, and cystic ovary disease as one category of 3 related
      noninfectious ovary disorders were studied. Data were analyzed using a threshold
      model that included herd, calving year, season of calving, and parity as cross
      classified fixed factors; and sire and cow within sires as random effects. Days
      at risk and days in milk at the beginning of a record were included by fitting
      the days as continuous covariates in the model. A heritability value of 0.202 +/-
      0.083 was estimated for generalized immunity. Heritability values of 0.141 and
      0.161 were estimated for uterine infection and mastitis, respectively.
      Heritability of single noninfectious disorders ranged from 0.087 to 0.349. The
      amount of additive genetic variance recovered in the underlying scale of
      noninfectious disorders tended to zero when combining multiple conditions. The
      study supports combining infectious diseases into categories of interest but we
      do not recommend the same approach for noninfectious disorders.

PMID- 15738255
TI  - Data subsetting strategies for estimation of across-country genetic correlations.
AB  - International genetic evaluation of dairy cattle requires estimation of genetic
      correlations among populations to account for genotype-environment interaction.
      Simultaneous estimation of across-country genetic correlations among all
      populations of a widespread breed, such as the Holstein breed is, however,
      hampered by connectedness problems and computational challenges. The purpose of
      this study was to examine the effects of using bulls with across-country,
      balanced distribution of daughters on estimates of genetic correlations. For this
      purpose, dairy cattle populations undergoing selection in 6 countries were
      simulated. Two population-size settings were used. In the small population-size
      setting (S-populations), the 6 simulated countries had 2000 cows and 20 young
      progeny testing bulls per generation. In the larger population-size setting (L
      populations), the 6 simulated countries had between 2000 and 64,000 cows and 20
      to 640 young progeny testing bulls per generation. The simulated (true) across
      country genetic correlations, depending on the country combination, varied
      between 0.5 and 0.9. Simulations comprised a base population and 10 generations
      and were replicated 16 times. Results for the S-populations were not conclusive.
      For the L-populations, results indicated that by use of data from a relatively
      small subset of bulls with distribution of daughters balanced across countries,
      genetic correlations could be estimated with very small bias (overall average of
      absolute value of bias across replicates was 0.03 for the L-populations). The
      suggested bull subsetting strategy would allow simultaneous estimation of across
      country genetic correlations to be computed for a larger number of countries and
      in a shorter window of time than was possible previously.

PMID- 15738256
TI  - Genetic parameter estimates of portuguese dairy cows for milk, fat, and protein
      using a spline test-day model.
AB  - A spline animal model was fitted to 152,103 test-day milk, fat, and protein yield
      records from 14,423 first-lactation cows. The models included age at calving and
      the herd-test-month as fixed effects. Model fitting was carried out using
      Restricted Maximum Likelihood with ASREML. For milk yield, the heritability at 18
      d in milk was 0.19, which increased to the maximum estimated value of 0.23 at
      midlactation and then decreased. On average, milk, fat, and protein yield
      heritabilities were 0.22, 0.14, and 0.19, respectively. For milk yield, all
      correlations were positive and ranged from 0.54 to 0.99 for the genetic component
      and from 0.32 to 0.78 for the phenotypic component. Genetic correlations were
      higher than phenotypic ones. For fat and protein yields, all genetic correlations
      were positive, ranging from 0.43 to 0.99. The phenotypic correlations for fat
      yield had the lowest correlations of the 3 traits. Curves of estimated breeding
      values for milk, fat, and protein over lactation had positive deviations from
      mean curves for sires with high genetic merit, but there was considerable
      variability in the shapes of the curves for different sires. More research is
      needed to compare the spline function with other mathematical functions used as
      submodels of lactation curve.

PMID- 15738257
TI  - The interaction of strain of Holstein-Friesian cows and pasture-based feed
      systems on milk yield, body weight, and body condition score.
AB  - Interactions between genotype and environment are becoming increasingly important
      as cattle genotypes are being managed in a diverse range of environments
      worldwide. The objective of this study was to investigate if there is an
      interaction of strain of Holstein-Friesian cows (HF) by grass-based feed system
      that affects milk production, body weight, and body condition score. Three
      strains of HF were compared on 3 pasture-based feed systems over 3 consecutive
      years. The 3 strains of HF were: high production North American, high durability
      North American, and New Zealand. The 3 grass-based feeding systems (FS) were: a
      high grass allowance system (MPFS), a high concentrate system (HCFS), and a high
      stocking rate system (HSFS). There was a separate farmlet for each FS and a total
      of 99, 117, and 117 animals were used in yr 1, 2, and 3 respectively, divided
      equally between strains of HF and FS. The high production cows produced the
      highest yield of milk, the New Zealand the lowest, and the high durability
      animals were intermediate. Milk fat and protein content were higher for the New
      Zealand strain than for the high production and high durability strains. The New
      Zealand strain had the lowest body weight and the highest condition score,
      whereas the high durability strain had the highest body weight, and the high
      production strain had the lowest condition score. There was a strain x FS
      interaction for yield of milk, fat, and protein. The milk production response to
      increased concentrate supplementation (MPFS vs. HCFS) was greater with both the
      high production and high durability strains (1.10 kg of milk/kg of concentrate
      for high production; 1.00 kg of milk/kg of concentrate for high durability) than
      the New Zealand strain (0.55 kg of milk/kg of concentrate). The results indicate
      that the optimum strain of HF will vary with feed system.

PMID- 15738258
TI  - A spreadsheet-based model demonstrating the nonuniform economic effects of
      varying reproductive performance in Ohio dairy herds.
AB  - A spreadsheet-based model was developed to estimate the economic effect of
      varying reproductive performance in dairy herds. Scenarios were created to model
      an average cow with respect to production, herd lifetime, and reproductive
      events. Average milk yield per day of life as well as lifetime calf and
      replacement heifer production were examined. Additional inputs representing milk,
      feed, semen, calf, and salvage prices were used to calculate net cash flow for
      each day of herd life for the average cow in a scenario. Economic comparison of
      different scenarios was accomplished using an equivalent annual cash flow
      (annuity) methodology.Herd performance measures and prices representative of Ohio
      dairy herds were used to establish a baseline average cow that had a 160-d
      calving-to-conception interval [days open (DO)]. Alternative scenarios that
      differed from baseline in DO, annual culling rate, and feed and milk prices were
      created to characterize the effects of changes. Under scenario inputs
      representative of typical Ohio dairy herds, the model indicated that a lower
      annual culling rate (25%) was preferable to higher annual culling rates (34 or
      45%). The model estimated maximum average milk yield per day of life to occur at
      110 DO. At 34% annual culling rate, calves and replacement heifers produced per
      lifetime declined as DO increased; beyond 150 DO, the modeled cow produced less
      than 1 replacement heifer per lifetime. The model also estimated a loss of $1.37
      per cow per year for a 1-d increase in DO beyond 160 d. At 20% higher feed and
      milk prices, the model estimated a loss of $1.52 per cow per year; at 20% lower
      feed and milk prices, the model estimated a loss of $1.23 per cow per year.
      Furthermore, the model suggested that the loss associated with a 1-d increase in
      DO changed as DO changed. Using baseline inputs, the model calculated losses for
      a 1-d increase of $0.44 per cow per year at 130 DO and $1.71 per cow per year at
      190 DO. The nonuniform nature of the cost of additional DO is important to
      veterinarians and producers. The implication is that inefficient reproduction
      becomes marginally more costly to producers as performance declines and warrants
      increased attention. Conversely, marginal benefits of improved reproduction
      decrease as performance improves. Herds with strong reproductive performance have
      less opportunity to capture economic benefits of improvement.

PMID- 15738259
TI  - Selection indices in Holstein cattle of various countries.
AB  - Fifteen countries, based on geographical representation, Interbull membership,
      and size of progeny testing programs, provided a brief description of national
      selection index and top bull listings from August 2003. Individual traits
      included in each selection index were grouped into 3 components as they related
      to production, durability, and health and reproduction. The relative emphasis for
      each component within the selection index, as well as the number of common bulls
      among top listings were compared across countries. Average relative emphasis for
      production, durability, and health and reproduction, across all countries, was
      59.5, 28, and 12.5%, respectively. The main difference between selection indices
      in various countries was the relative emphasis on production. Overall, the Danish
      S-Index had the most balanced emphasis across the 3 components, with 34% on
      production, 29% on durability, and 37% on health and reproduction. Broadening of
      breeding goals through recent changes to selection indices decreased the
      similarities of top bull listings across the various countries, with a slightly
      greater commonality among sires of top bulls.

PMID- 15738260
TI  - Performance of lactating dairy cows managed on pasture-based or in freestall barn
      feeding systems.
AB  - The objective was to compare productive and metabolic responses of lactating
      dairy cows managed on 2 pasture-based systems using a concentrate supplement (n =
      16) with those of a freestall housing system (n = 24). In a 259-d experiment, 3
      multiparous Holstein cows were assigned at calving to each of 4 replicates of 2
      pasture systems. For system 1, winter pastures were a mixture of rye, ryegrass,
      and crimson and red clover; summer pastures were pearl millet. Pasture system 2
      included a rye-ryegrass mixture during winter and bermudagrass during summer.
      Pregraze herbage mass averaged 2.3 and 3.6 Mg/ha for winter and summer pastures,
      respectively; however, during August through September, pearl millet pregraze
      mass was reduced to about 1 Mg/ha. Daily dry matter intake by cows on pasture
      averaged 24.7 kg/d in winter and 19.0 kg/d in summer, of which 55% was from
      pasture; that of cows in confined-housing averaged 23.6 kg/d. Cows in confinement
      produced 19% more milk (29.8 vs. 25.1 kg/d) than those on pasture systems.
      Differences in concentration of milk fat, protein, or urea N were not detected
      among treatment groups. Grazing cows lost more body weight than confined cows
      (113 vs. 58 kg) and had lower concentrations of plasma glucose in the early weeks
      postpartum. Despite greater milk yield by cows housed in freestalls, milk income
      minus feed costs including that of pasture was similar for the 3 management
      systems. Although these pasture systems might be a viable management system in
      the southeastern US, extensive loss of body weight immediately postpartum for
      pasture-based cows are a potential concern.

PMID- 15738261
TI  - Conservation of boundary extension mechanisms between plants and animals.
AB  - Locomotion clearly sets plants and animals apart. However, recent studies in
      higher plants reveal cell-biological and molecular features similar to those
      observed at the leading edge of animal cells and suggest conservation of boundary
      extension mechanisms between motile animal cells and nonmotile plant cells.

PMID- 15738262
TI  - Crossing over is coupled to late meiotic prophase bivalent differentiation
      through asymmetric disassembly of the SC.
AB  - Homologous chromosome pairs (bivalents) undergo restructuring during meiotic
      prophase to convert a configuration that promotes crossover recombination into
      one that promotes bipolar spindle attachment and localized cohesion loss. We have
      imaged remodeling of meiotic chromosome structures after pachytene exit in
      Caenorhabditis elegans. Chromosome shortening during diplonema is accompanied by
      coiling of chromosome axes and highly asymmetric departure of synaptonemal
      complex (SC) central region proteins SYP-1 and SYP-2, which diminish over most of
      the length of each desynapsing bivalent while becoming concentrated on axis
      segments distal to the single emerging chiasma. This and other manifestations of
      asymmetry along chromosomes are lost in synapsis-proficient crossover-defective
      mutants, which often retain SYP-1,2 along the full lengths of coiled diplotene
      axes. Moreover, a gamma-irradiation treatment that restores crossovers in the spo
      11 mutant also restores asymmetry of SYP-1 localization. We propose that
      crossovers or crossover precursors serve as symmetry-breaking events that promote
      differentiation of subregions of the bivalent by triggering asymmetric
      disassembly of the SC.

PMID- 15738263
TI  - Long-range cooperative binding of kinesin to a microtubule in the presence of
      ATP.
AB  - Interaction of kinesin-coated latex beads with a single microtubule (MT) was
      directly observed by fluorescence microscopy. In the presence of ATP, binding of
      a kinesin bead to the MT facilitated the subsequent binding of other kinesin
      beads to an adjacent region on the MT that extended for micrometers in length.
      This cooperative binding was not observed in the presence of ADP or 5'
      adenylylimidodiphosphate (AMP-PNP), where binding along the MT was random.
      Cooperative binding also was induced by an engineered, heterodimeric kinesin,
      WT/E236A, that could hydrolyze ATP, yet remained fixed on the MT in the presence
      of ATP. Relative to the stationary WT/E236A kinesin on a MT, wild-type kinesin
      bound preferentially in close proximity, but was biased to the plus-end
      direction. These results suggest that kinesin binding and ATP hydrolysis may
      cause a long-range state transition in the MT, increasing its affinity for
      kinesin toward its plus end. Thus, our study highlights the active involvement of
      MTs in kinesin motility.

PMID- 15738264
TI  - PATJ regulates tight junction formation and polarity in mammalian epithelial
      cells.
AB  - Recent studies have revealed an important role for tight junction protein
      complexes in epithelial cell polarity. One of these complexes contains the apical
      transmembrane protein, Crumbs, and two PSD95/discs large/zonula occludens domain
      proteins, protein associated with Lin seven 1 (PALS1)/Stardust and PALS1
      associated tight junction protein (PATJ). Although Crumbs and PALS1/Stardust are
      known to be important for cell polarization, recent studies have suggested that
      Drosophila PATJ is not essential and its function is unclear. Here, we find that
      PATJ is targeted to the apical region and tight junctions once cell polarization
      is initiated. We show using RNAi techniques that reduction in PATJ expression
      leads to delayed tight junction formation as well as defects in cell
      polarization. These effects are reversed by reintroduction of PATJ into these
      RNAi cells. This study provides new functional information on PATJ as a polarity
      protein and increases our understanding of the Crumbs-PALS1-PATJ complex function
      in epithelial polarity.

PMID- 15738265
TI  - The de novo centriole assembly pathway in HeLa cells: cell cycle progression and
      centriole assembly/maturation.
AB  - It has been reported that nontransformed mammalian cells become arrested during
      G1 in the absence of centrioles (Hinchcliffe, E., F. Miller, M. Cham, A.
      Khodjakov, and G. Sluder. 2001. Science. 291:1547-1550). Here, we show that
      removal of resident centrioles (by laser ablation or needle microsurgery) does
      not impede cell cycle progression in HeLa cells. HeLa cells born without
      centrosomes, later, assemble a variable number of centrioles de novo. Centriole
      assembly begins with the formation of small centrin aggregates that appear during
      the S phase. These, initially amorphous "precentrioles" become morphologically
      recognizable centrioles before mitosis. De novo-assembled centrioles mature
      (i.e., gain abilities to organize microtubules and replicate) in the next cell
      cycle. This maturation is not simply a time-dependent phenomenon, because de novo
      formed centrioles do not mature if they are assembled in S phase-arrested cells.
      By selectively ablating only one centriole at a time, we find that the presence
      of a single centriole inhibits the assembly of additional centrioles, indicating
      that centrioles have an activity that suppresses the de novo pathway.

PMID- 15738266
TI  - N-myristoylation determines dual targeting of mammalian NADH-cytochrome b5
      reductase to ER and mitochondrial outer membranes by a mechanism of kinetic
      partitioning.
AB  - Mammalian NADH-cytochrome b5 reductase (b5R) is an N-myristoylated protein that
      is dually targeted to ER and mitochondrial outer membranes. The N-linked
      myristate is not required for anchorage to membranes because a stretch of
      hydrophobic amino acids close to the NH2 terminus guarantees a tight interaction
      of the protein with the phospholipid bilayer. Instead, the fatty acid is required
      for targeting of b5R to mitochondria because a nonmyristoylated mutant is
      exclusively localized to the ER. Here, we have investigated the mechanism by
      which N-linked myristate affects b5R targeting. We find that myristoylation
      interferes with interaction of the nascent chain with signal recognition
      particle, so that a portion of the nascent chains escapes from cotranslational
      integration into the ER and can be post-translationally targeted to the
      mitochondrial outer membrane. Thus, competition between two cotranslational
      events, binding of signal recognition particle and modification by N
      myristoylation, determines the site of translation and the localization of b5R.

PMID- 15738267
TI  - Dynamic ergosterol- and ceramide-rich domains in the peroxisomal membrane serve
      as an organizing platform for peroxisome fusion.
AB  - We describe unusual ergosterol- and ceramide-rich (ECR) domains in the membrane
      of yeast peroxisomes. Several key features of these detergent-resistant domains,
      including the nature of their sphingolipid constituent and its unusual
      distribution across the membrane bilayer, clearly distinguish them from well
      characterized detergent-insoluble lipid rafts in the plasma membrane. A distinct
      set of peroxisomal proteins, including two ATPases, Pex1p and Pex6p, as well as
      phosphoinositide- and GTP-binding proteins, transiently associates with the
      cytosolic face of ECR domains. All of these proteins are essential for the fusion
      of the immature peroxisomal vesicles P1 and P2, the earliest intermediates in a
      multistep pathway leading to the formation of mature, metabolically active
      peroxisomes. Peroxisome fusion depends on the lateral movement of Pex1p, Pex6p,
      and phosphatidylinositol-4,5-bisphosphate-binding proteins from ECR domains to a
      detergent-soluble portion of the membrane, followed by their release to the
      cytosol. Our data suggest a model for the multistep reorganization of the
      multicomponent peroxisome fusion machinery that transiently associates with ECR
      domains.

PMID- 15738268
TI  - Sunday Driver links axonal transport to damage signaling.
AB  - Neurons transmit long-range biochemical signals between cell bodies and distant
      axonal sites or termini. To test the hypothesis that signaling molecules are
      hitchhikers on axonal vesicles, we focused on the c-Jun NH2-terminal kinase (JNK)
      scaffolding protein Sunday Driver (syd), which has been proposed to link the
      molecular motor protein kinesin-1 to axonal vesicles. We found that syd and JNK3
      are present on vesicular structures in axons, are transported in both the
      anterograde and retrograde axonal transport pathways, and interact with kinesin-I
      and the dynactin complex. Nerve injury induces local activation of JNK, primarily
      within axons, and activated JNK and syd are then transported primarily
      retrogradely. In axons, syd and activated JNK colocalize with p150Glued, a
      subunit of the dynactin complex, and with dynein. Finally, we found that injury
      induces an enhanced interaction between syd and dynactin. Thus, a mobile axonal
      JNK-syd complex may generate a transport-dependent axonal damage surveillance
      system.

PMID- 15738270
TI  - Sensory control and organization of neural networks mediating coordination of
      multisegmental organs for locomotion.
AB  - It is well established that locomotor patterns result from the interaction
      between central pattern generating networks in the nervous system, local feedback
      from sensory neurons about movements and forces generated in the locomotor
      organs, and coordinating signals from neighboring segments or appendages. This
      review addresses the issue of how the movements of multi-segmented locomotor
      organs are coordinated and provides an overview of recent advances in
      understanding sensory control and the internal organization of central pattern
      generating networks that operate multi-segmented locomotor organs, such as a
      walking leg. Findings from the stick insect and the cat are compared and
      discussed in relation to new findings on the lamprey swimming network. These
      findings support the notion that common schemes of sensory feedback are used for
      generating walking and that central neural networks controlling multi-segmented
      locomotor organs generally encompass multiple central pattern generating networks
      that correspond with the segmental structure of the locomotor organ.

PMID- 15738269
TI  - Regulation of the interaction between PIPKI gamma and talin by proline-directed
      protein kinases.
AB  - The interaction of talin with phosphatidylinositol(4) phosphate 5 kinase type I
      gamma (PIPKI gamma) regulates PI(4,5)P2 synthesis at synapses and at focal
      adhesions. Here, we show that phosphorylation of serine 650 (S650) within the
      talin-binding sequence of human PIPKI gamma blocks this interaction. At synapses,
      S650 is phosphorylated by p35/Cdk5 and mitogen-activated protein kinase at rest,
      and dephosphorylated by calcineurin upon stimulation. S650 is also a substrate
      for cyclin B1/Cdk1 and its phosphorylation in mitosis correlates with focal
      adhesion disassembly. Phosphorylation by Src of the tyrosine adjacent to S650
      (Y649 in human PIPKI gamma) was shown to enhance PIPKI gamma targeting to focal
      adhesions (Ling, K., R.L. Doughman, V.V. Iyer, A.J. Firestone, S.F. Bairstow,
      D.F. Mosher, M.D. Schaller, and R.A. Anderson. 2003. J. Cell Biol. 163:1339
      1349). We find that Y649 phosphorylation does not stimulate directly PIPKI gamma
      binding to talin, but may do so indirectly by inhibiting S650 phosphorylation.
      Conversely, S650 phosphorylation inhibits Y649 phosphorylation by Src. The
      opposite effects of the phosphorylation of Y649 and S650 likely play a critical
      role in regulating synaptic function as well as the balance between cell adhesion
      and cell motility.

PMID- 15738271
TI  - An argument for using ethologically "natural" behaviors as estimates of
      unobservable sensory processes. Focus on "Sound localization performance in the
      cat: the effect of restraining the head".

PMID- 15738272
TI  - Modulation of spontaneous firing in rat subthalamic neurons by 5-HT receptor
      subtypes.
AB  - The subthalamic nucleus (STN) is considered to be one of the driving forces in
      the basal ganglia circuit. The STN is innervated by serotonergic afferents from
      the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We
      investigated the effects of 5-HT and 5-HT receptor subtype agonists and
      antagonists on the firing properties of STN neurons in rat brain slices. We used
      cell-attached, perforated-patch, and whole cell recording techniques to detect
      changes in firing frequency and pattern and electrical membrane properties. Due
      to the depolarization of membrane potential caused by reduced potassium
      conductance, 5-HT (10 microM) increased the firing frequency of STN neurons
      without changing their firing pattern. Cadmium failed to occlude the effect of 5
      HT on firing frequency. 5-HT had no effect on afterhyperpolarization current.
      These results indicated that the 5-HT action was not mediated by high-voltage
      activated calcium channel currents and calcium-dependent potassium currents. 5-HT
      had no effect on hyperpolarization-activated cation current (I(H)) amplitude and
      voltage-dependence of I(H) activation, suggesting that I(H) was not involved in 5
      HT-induced excitation. The increased firing by 5-HT was mimicked by 5-HT(2/4)
      receptor agonist alpha-methyl-5-HT and was partially mimicked by 5-HT2 receptor
      agonist DOI or 5-HT4 receptor agonist cisapride. The 5-HT action was partially
      reversed by 5-HT4 receptor antagonist SB 23597-190, 5-HT2 receptor antagonist
      ketanserin, and 5-HT2C receptor antagonist RS 102221. Our data indicate that 5-HT
      has significant ability to modulate membrane excitability in STN neurons;
      modulation is accomplished by decreasing potassium conductance by activating 5
      HT4 and 5-HT2C receptors.

PMID- 15738273
TI  - Ten- to 12-Hz EEG oscillation in the rat hippocampus and rhinal cortex that is
      modulated by environmental familiarity.
AB  - A characteristic feature of the electroencephalogram (EEG) of the hippocampus and
      rhinal (entorhinal and perirhinal) cortex of the freely moving rat is theta
      rhythm, a prominent oscillation of approximately 8 Hz. Here we demonstrate that a
      novel rhythm that occurs at the border between the theta and alpha range of
      frequencies (10-12 Hz) can also be recorded from these structures. This rhythm
      (referred to here as "flutter") appears to be of non-theta origin as it can occur
      simultaneously with theta and it does not display the phase inversion across the
      hippocampus that characterizes theta activity. Flutter is observed in locomoting
      rats that are foraging for food reward in a familiar environment. Flutter
      disappears when rats are placed into a novel (although visually identical)
      environment, even though their foraging behavior does not appear to be altered.
      It is, at the present time, unclear what function flutter subserves. The presence
      of flutter may relate to a particular motivational state of the animal or to a
      particular type of information processing.

PMID- 15738274
TI  - Pulse rise time but not duty cycle affects the temporal selectivity of neurons in
      the anuran midbrain that prefer slow AM rates.
AB  - Recovery-type auditory neurons in the anuran inferior colliculus (IC) respond
      with band-pass or low-pass selectivity for sinusoidal AM. These cells respond to
      each modulation cycle at slow AM rates and respond only at the onset of fast AM
      or pulse repetition rate (PRR) stimuli, failing to recover from the effects of
      early pulses. This selectivity is not altered by changes in pulse duty cycle. The
      recovery process is governed therefore by the interpulse interval and not the
      dimension of the gap between sound pulses. Most of these neurons preferred fast
      rise times, which is characteristic of the sound pulses in the calls of Hyla
      regilla and Rana pipiens, the two species selected for this study.

PMID- 15738275
TI  - Histamine compartments of the Drosophila brain with an estimate of the quantum
      content at the photoreceptor synapse.
AB  - Reliable estimates of the quantum size in histaminergic neurons are not
      available. We have exploited two unusual opportunities in the fly's (Drosophila
      melanogaster) visual system to make such determinations for histaminergic
      photoreceptor synapses: 1) the possibility to microdissect successively from
      whole fly heads freeze-dried in acetone: the compound eyes; the first optic
      neuropils, or lamina; and the rest of the brain; and 2) the uniform sheaves of
      lamina synaptic terminals of photoreceptors R1-R6. We used this organization to
      count scrupulously the numbers of 30-nm synaptic vesicles from electron
      micrographs of R1-R6 profiles, and from microdissections we determined the
      regional contents of histamine in the compound eye, lamina, and central brain.
      Total head histamine averages 1.98 ng of which 9% was lost after freeze-drying in
      acetone and a further 28% after the brain was microdissected. Of the remainder,
      71% was in the eye and lamina. Assuming that histamine loss from the tissue
      occurred mostly by diffusion evenly distributed among all regions, the overall
      lamina content of the head would be 0.1935 ng before dissection. From published
      values for the volumes of the brain's compartments, the computed regional
      concentrations of histamine are highest in the lamina (4.35 mM) because of the
      terminals of R1-R6. The concentration in the retina is approximately 13% that in
      the lamina, suggesting that most histamine is vesicular. There are approximately
      43,500 +/- 7,400 (SD) synaptic vesicles per terminal and, if all histamine is
      allocated equally and exclusively among these, the vesicle contents would be 858
      +/- 304 x 10(-21) moles or approximately 5,000 +/- 1,800 (SD) molecules at an
      approximate concentration of 670 mM. These values are compared with the vesicle
      contents at synapses using acetylcholine and catecholamines.

PMID- 15738276
TI  - Complex expression and localization of inactivating Kv channels in cultured
      hippocampal astrocytes.
AB  - Voltage-gated potassium channels are well established as critical for setting
      action potential frequency, membrane potential, and neurotransmitter release in
      neurons. However, their role in the "nonexcitable" glial cell type is yet to be
      fully understood. We used whole cell current kinetics, pharmacology,
      immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal
      astrocyte cultures to better understand its function. Pharmacological analysis
      suggests that approximately 70, 10, and <5% of total A current is associated with
      Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics
      provide evidence for a significant contribution of KChIP accessory proteins to
      astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to
      astrocytic processes and the Shal Kv4.3 channel to soma suggest that these
      channels serve a specific function. Given this complex A-type channel expression
      pattern, we assessed the role of A currents in membrane voltage oscillations in
      response to current injections. Although TEA-sensitive delayed-rectifying
      currents are involved in the extent of repolarization, 4-AP-sensitive A currents
      serve to increase the rate. As in neurons, this effect may enable astrocytes to
      respond rapidly to high-frequency synaptic events. Our results indicate that
      hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits
      with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be
      specifically localized to subcellular membrane compartments. Function of these
      channels remains to be determined in a physiological setting. However, this study
      suggests that they enable astrocytes to respond rapidly with membrane voltage
      oscillations to high-frequency incoming signals, possibly synchronizing astrocyte
      function to neuronal activity.

PMID- 15738277
TI  - Striatal inhibition of nociceptive responses evoked in trigeminal sensory neurons
      by tooth pulp stimulation.
AB  - The noxious evoked response in trigeminal sensory neurons was studied to address
      the role of striatum in the control of nociceptive inputs. In urethane
      anesthetized rats, the jaw opening reflex (JOR) was produced by suprathreshold
      stimulation of the tooth pulp and measured as electromyographic response in the
      digastric muscle, with simultaneous recording of noxious responses in single unit
      neurons of the spinal trigeminal nucleus pars caudalis (Sp5c). The microinjection
      of glutamate (80 etamol/0.5 microl) into striatal JOR inhibitory sites
      significantly decreased the A delta and C fiber-mediated-evoked response (53 +/-
      4.2 and 43.6 +/- 6.4% of control value, P < 0.0001) in 92% (31/34) of nociceptive
      Sp5c neurons. The microinjection of the solvent was ineffective, as was
      microinjection of glutamate in sites out of the JOR inhibitory ones. In another
      series of experiments, simultaneous single unit recordings were performed in the
      motor trigeminal nucleus (Mo5) and the Sp5c nucleus. Microinjection of glutamate
      decreased the noxious-evoked response in Sp5c and Mo5 neurons in parallel with
      the JOR, without modifying spontaneous neuronal activity of trigeminal
      motoneurons (n = 8 pairs). These results indicate that the striatum could be
      involved in the modulation of nociceptive inputs and confirm the role of the
      basal ganglia in the processing of nociceptive information.

PMID- 15738278
TI  - Teaching old drugs new tricks: asthma therapy adjusted by patient perception or
      noninvasive markers.

PMID- 15738279
TI  - Endoscopic ultrasound-guided biopsy in the chest: little to lose, much to gain.

PMID- 15738280
TI  - Obliterative bronchiolitis in haematopoietic stem cell transplantation: can it be
      treated?

PMID- 15738281
TI  - Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of
      sarcoidosis.
AB  - The objective of the current study was to assess the yield of endoscopic
      ultrasound (EUS)-guided fine-needle aspiration (FNA) for the diagnosis of
      sarcoidosis in a large patient group. Bronchoscopy with transbronchial lung
      biopsy (TBLB) is nondiagnostic in 30% of patients with suspected sarcoidosis and
      has a risk of pneumothorax and haemoptysis. In order to obtain a diagnosis,
      mediastinoscopy is often performed as the next diagnostic procedure. EUS-FNA
      provides a nonsurgical alternative for the demonstration of noncaseating
      granulomas by aspirating mediastinal lymph nodes from the oesophagus. In total,
      51 patients with suspected sarcoidosis stage I and II underwent EUS-FNA. Thirty
      six patients (71%) previously underwent a nondiagnostic bronchoscopy. All
      patients were clinically followed (median 18 months) and surgical-pathological
      verification occurred in those patients with EUS aspirates that contained
      unrepresentative material. EUS-FNA demonstrated noncaseating granulomas without
      necrosis in 41 of 50 patients (82%) with the final diagnosis of sarcoidosis.
      Specific ultrasound features of clustered, well-demarcated iso-echoic lymph nodes
      were observed in 64% of patients with sarcoidosis. No complications occurred.
      Endoscopic ultrasound-guided fine-needle aspiration has a high yield in
      diagnosing sarcoidosis and qualifies as the next diagnostic step after a
      nondiagnostic bronchoscopy. The current authors expect that endoscopic ultrasound
      guided fine-needle aspiration will reduce the number of mediastinoscopies for the
      diagnosis of sarcoidosis dramatically.

PMID- 15738282
TI  - The accuracy of EUS-FNA in assessing mediastinal lymphadenopathy and staging
      patients with NSCLC.
AB  - Optimal management of nonsmall cell lung cancer (NSCLC) depends on tissue
      diagnosis and accurate staging. Endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) is minimally invasive and provides cytological confirmation
      of malignant mediastinal disease. The aim was to assess the accuracy of EUS-FNA
      in cases of enlarged mediastinal lymphadenopathy (LN) of unknown aetiology and in
      the staging of NSCLC. A total of 52 consecutive patients with stage I-IIIb NSCLC
      or enlarged mediastinal LN of unknown aetiology underwent EUS-FNA. Negative
      results were confirmed with a surgical procedure: mediastinoscopy, video-assisted
      thoracic surgery (VATS) or lobectomy with systematic mediastinal lymph node
      dissection. In total, 34 patients had EUS-FNA performed for diagnosis, whilst the
      remaining 18 had EUS-FNA for staging. The overall sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV) and accuracy
      (95% confidence interval) were 93% (77-99), 100% (78-100), 100% (87-100), 88% (63
      99) and 95% (84-99), respectively. When EUS-FNA was used in patients with NSCLC,
      the sensitivity, specificity, PPV, NPV and accuracy were 92% (73-99), 100% (69
      100), 100% (85-100), 83% (51-98) and 94% (80-99), respectively. For mediastinal
      LN of unknown aetiology, no malignant disease was missed. Endoscopic ultrasound
      guided fine-needle aspiration is an accurate tool for assessing mediastinal lymph
      node involvement in nonsmall cell lung cancer and in the diagnosis of unexplained
      mediastinal lymphadenopathy. Endoscopic ultrasound-guided fine-needle aspiration
      is a minimally invasive procedure that can be used as an adjunct or alternative
      to mediastinoscopy.

PMID- 15738283
TI  - Endobronchial and endoscopic ultrasound-guided real-time fine-needle aspiration
      for mediastinal staging.
AB  - Accurate staging of the mediastinum in lung cancer is essential for optimising
      treatment strategies. Conventional transbronchial needle aspiration (TBNA) is a
      blind procedure, reliant upon prior computed tomography (CT) or ultrasound
      imaging, but has low sensitivity. The current study reports the initial
      experience of using a prototype endobronchial ultrasound (EBUS) probe that allows
      TBNA under real-time imaging. In 20 patients selected by CT scanning, a linear
      array ultrasound bronchoscope was used to visualise paratracheal and hilar lymph
      nodes, and TBNA was performed under direct ultrasonic control. In seven cases,
      sequential endoscopic ultrasound (EUS) was used to assess postero-inferior
      mediastinal lymph nodes. All procedures were performed under conscious sedation.
      EBUS-TBNA was undertaken in 18 out of 20 cases and EUS-guided fine-needle
      aspiration in six out of seven cases. Cytology showed node (N)2/N3 disease in 11
      out of 18 EBUS-TBNA cases and provided a primary diagnosis for eight patients.
      EBUS-TBNA cytology was negative in six cases, which was confirmed by
      mediastinoscopy or clinical follow-up in four. EUS provided additional
      information in all cases. There were no procedural complications. Sensitivity,
      specificity and accuracy for EBUS-TBNA were 85%, 100% and 89%, respectively. In
      conclusion, endobronchial ultrasound with real-time transbronchial needle
      aspiration offers improved sensitivity and accuracy for staging of the middle
      mediastinum, and, combined with endoscopic ultrasound, should allow investigation
      of the majority of the mediastinum.

PMID- 15738284
TI  - Time-based gene expression programme following diaphragm injury in a rat model.
AB  - It was hypothesised that diaphragm injury activates a time-based programme of
      gene expression in muscle repair. Gene expression of different substances, such
      as proteases (calpain 94 (p94)), transcription factors (myogenin and cFos),
      growth factors (both basic fibroblast growth factor (bFGF) and insulin-like
      growth factor (IGF)-II), and structural proteins (myosin heavy chain (MHC) and
      titin), was quantified by RT-PCR in rat diaphragms exposed to caffeine-induced
      injury. Injured and noninjured (control) rat hemidiaphragms were excised at
      different time points (1-240 h). In injured hemidiaphragms, in comparison with
      control muscles, p94 expression levels peaked at 1 h post-injury (PI), cFos mRNA
      levels began to rise, after an initial dip, and peaked at 96 h PI, while myogenin
      mRNA levels started to increase as early as 12 h PI, IGF-II mRNA levels initially
      decreased until 48 h PI and increased thereafter, peaking at 72 h PI, bFGF mRNA
      levels rose to a maximum at 96 h PI, and MHC and titin mRNA levels were
      significantly elevated at 72 h PI. Caffeine-induced diaphragm injury is followed
      by a time-based expression programme of different genes tailored to meet muscle
      repair needs.

PMID- 15738285
TI  - Skeletal muscle microbiopsy: a validation study of a minimally invasive
      technique.
AB  - The study of the peripheral skeletal muscle function in patients with chronic
      obstructive pulmonary disease (COPD) is of growing interest, but often requires
      biopsies, usually with the Bergstrom technique. The current study was designed to
      test the validity of a minimally invasive technique: the microbiopsy. In 17
      patients with COPD and four normal subjects, two specimens of the vastus
      lateralis were taken percutaneously under local anaesthesia, one with a 16-gauge
      needle (microbiopsy) and the other with the Bergstrom needle. The enzymatic
      activity of citrate synthase (CS) and phosphofructokinase (PFK), and the myosin
      heavy chain (MyoHC) composition were measured for both techniques. The subjects
      reported no pain or much less with the microbiopsy compared with the Bergstrom
      biopsy. The microbiopsy sample weight reached 55+/-17 mg. The two techniques
      showed excellent agreement for CS activity and MyoHC composition. The PFK
      activity did not differ statistically between the techniques, but the agreement
      was moderate. The agreement between both biopsy techniques was stable over time.
      The median (range) fibre number within the microbiopsy specimens was 144 (38
      286). In conclusion, the current study shows the feasibility and validity of a
      minimally invasive muscle biopsy technique that appears more comfortable for
      subjects, compared with the Bergstrom technique.

PMID- 15738286
TI  - Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by an excessive
      inflammatory response to inhaled particles, mostly tobacco smoking. Although
      inflammation is present in all smokers, only a percentage of them develop COPD. T
      lymphocytes are important effector and regulatory cells that participate actively
      in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)
      alpha beta (CD4+ and CD8+) and TCR-gamma delta T-lymphocytes. The latter
      represent a small percentage of the total T-cell population, but play a key role
      in tissue repair and mucosal homeostasis. To investigate TCR-alpha beta (CD4+ and
      CD8+) and TCR-gamma delta T-lymphocytes in COPD, the present authors determined,
      by flow cytometry, the distribution of both subpopulations in peripheral blood
      and bronchoalveolar lavage (BAL) samples obtained from patients with COPD,
      smokers with normal lung function and never-smokers. The present study found
      that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was
      similar in all three groups; 2) compared with nonsmokers, gamma delta T
      lymphocytes were significantly increased in smokers with preserved lung function;
      and 3) this response was blunted in patients with COPD. These results highlight a
      novel, potentially relevant, pathogenic mechanism in chronic obstructive
      pulmonary disease.

PMID- 15738287
TI  - Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking
      cessation.
AB  - There is heterogeneity in the propensity of smokers to develop chronic
      obstructive pulmonary disease (COPD), and improved treatment strategies are
      hindered by limited understanding of COPD pathogenesis, especially as distinct
      from the effects of smoking per se. Although apoptosis is essential for tissue
      homeostasis, increased apoptosis may cause tissue damage and inflammation. This
      study addressed whether airway T-lymphocytes and airway epithelial cells (AEC)
      show an increased likelihood of undergoing apoptosis in COPD and if this was
      related to smoking. Apoptosis (7-amino-actinomycin D, Annexin, single-stranded
      DNA and caspase), Bcl-2, Bax and p53 were assessed in cells obtained from
      bronchial bushing and bronchoalveolar lavage from ex- and continuing smokers with
      COPD, and nonsmoking controls, using flow cytometry. A mean 87% increase in
      apoptosis of AEC and a 103% increase in T-lymphocyte apoptosis were found in
      COPD. There were no significant differences in apoptosis of AEC between current
      and ex-smokers with COPD. Apoptosis may contribute to chronic obstructive
      pulmonary disease pathogenesis, and continued excess apoptosis after smoking
      cessation may offer a new target for therapeutic interventions. Whether the
      persistence of increased apoptosis after smoking cessation results from changes
      in the pulmonary milleau after years of noxious insult, or whether some
      individuals have a natural predisposition toward increased apoptosis and possible
      development of chronic obstructive pulmonary disease remains to be determined.

PMID- 15738288
TI  - Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopy.
AB  - Airway inflammation is an early feature of asthma. Early detection and anti
      inflammatory treatment may have important therapeutic impact. Exhaled nitric
      oxide is a noninvasive marker of airway inflammation. The current study
      investigated the association between exhaled nitric oxide and asthma, wheezing
      phenotypes, atopy and blood eosinophilia in a large group of 4-yr-old children
      from the general population. All children participated in the Prevention and
      Incidence of Asthma and Mite Allergy study, a birth cohort study of high-risk
      (atopic mother) and low-risk children in the Netherlands. Nitric oxide levels
      were successfully determined in 429 children. Although there was overlap in the
      distribution of values of children with and without asthma or atopy, mean values
      were higher in children with atopy or doctor's diagnosed asthma (geometric mean
      (ppb) 9.4 and 10.0, respectively) as compared to those without (7.7 and 7.9).
      Values were highest in atopic symptomatic children. Values were not associated
      with wheezing phenotype or blood eosinophilia. This study is one of the few large
      scale epidemiological studies among 4-yr-old children from the general population
      showing that children with symptoms of asthma and atopy have higher levels of
      exhaled nitric oxide than those without.

PMID- 15738289
TI  - Determinants of airway responsiveness to histamine in children.
AB  - Increased airway responsiveness (AR) is associated with asthma, but not all
      individuals with increased AR have asthma. The aim of this study was to identify
      factors, other than physician-diagnosed asthma (PDA), which are associated with
      increased AR. In a longitudinal study, data were collected on atopy and lower
      respiratory tract illness (LRTI) in infancy, and AR (expressed as dose-response
      slope (DRS)), atopy, tobacco-smoke exposure and PDA in childhood. At age 6 yrs,
      DRS was assessed in 102 children, of whom 22 (22%) had PDA; the corresponding
      figures at 11 yrs of age were 176 and 29 (15%). At age 6 yrs, DRS was
      significantly associated with PDA, current atopy and parental smoking (n = 83).
      At age 11 yrs, DRS was significantly associated with PDA, current atopy and LRTI
      in the first six months (n = 75). There was a significant positive interaction
      between atopy at age 12 months and PDA age 11 yrs. In conclusion, these data
      suggest that factors other than asthma or atopy may determine the level of airway
      responsiveness in children. In children with asthma, airway responsiveness may be
      influenced by the early onset of atopy. The current findings may explain the
      inconsistent relationship between airway responsiveness and asthma.

PMID- 15738290
TI  - The CFTR 3849+10kbC->T and 2789+5G->A alleles are associated with a mild CF
      phenotype.
AB  - Most cystic fibrosis (CF) transmembrane receptor mutations are rare. The French
      CF Registry offers an opportunity to study the genotype-phenotype relationship of
      these rare alleles. Since 1992, 39 CF patients carrying one copy of the
      3849+10kbC->T mutation and 88 the 2789+5G->A allele have been seen at least once
      in a CF care centre. Among them, 16 carrying the 3849+10kbC->T/Delta F508
      genotype and 34 with the 2789+5G->A/Delta F508 genotype were seen in 2000. Their
      age at diagnosis, sweat chloride concentration, anthropometric and lung function
      results, and clinical aspects were compared with those homozygous for the Delta
      F508 mutation matched for sex, age and CF care centre. Major differences, most of
      them statistically significant, in the age at diagnosis, prevalence of pancreatic
      insufficiency, and other clinical signs, anthropometric and lung function
      measures were observed between both compound heterozygote groups and their
      matched Delta F508/Delta F508 groups. The mean sweat chloride concentration was
      also lower (close to normal values) among 3849+10kbC->T/Delta F508 patients, but
      not among 2789+5G->A/Delta F508 patients. In conclusion, both mutations studied
      here are associated with a milder course of cystic fibrosis disease. The
      3849+10kbC->T and 2789+5G->A alleles are splice site mutations, leading to
      abnormal mRNA; however, a small amount of normally spliced transcripts can also
      be detected. The presence of these small amounts of normal cystic fibrosis
      transmembrane receptor protein in these cystic fibrosis patients is likely to be
      responsible for the milder severity of disease and a better life expectancy.

PMID- 15738291
TI  - Epidemiology of Pseudomonas aeruginosa in a cystic fibrosis rehabilitation
      centre.
AB  - Pseudomonas aeruginosa is the leading pathogen in cystic fibrosis (CF) lungs.
      Since there is great concern about clonal spread in CF centres, this study
      examined the P. aeruginosa genotypes of colonised residents of a CF
      rehabilitation centre. The isolates from the sputum of 76 P. aeruginosa-colonised
      patients were genotyped by fluorescent amplified fragment length polymorphism on
      arrival and departure. A total of 71 different P. aeruginosa genotypes were
      identified from 749 isolates. Forty-nine patients had one genotype, 20 had two
      genotypes and seven had three. Forty-four patients had one or more genotypes in
      common with other patients (i.e. cluster types). Thirty-two patients were
      colonised by a single genotype not shared by any other patient. Thirty-eight of
      the 44 patients with a cluster type already carried their cluster type strain(s)
      on arrival. Patient-to-patient transmission could not be excluded for eight
      patients. For five of these, this infection was transient. None of the
      environmental P. aeruginosa isolates had a genotype similar to the patients'
      genotypes. In summary, most patients were colonised by only one or two P.
      aeruginosa genotypes and the risk of persistent patient-to-patient transmission
      was low during the study period (4%). Most patients with a cluster-type strain
      carried this strain on arrival, indicating that transmission could have happened
      in the past. No environmental contamination could be established.

PMID- 15738292
TI  - Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology.
AB  - As a defective anti-polysaccharide response can exist in the absence of an
      immunoglobulin deficiency, a series of 26 patients with bronchiectasis of unknown
      aetiology was vaccinated with a 23-valent pneumococcal polysaccharide vaccine.
      All patients suffered from recurrent respiratory tract infections. When measuring
      total antibody levels to pneumococcal serotypes 3, 4 and 9, a normal
      polysaccharide antibody response was found in 22 patients. However, only 11 of
      these subjects showed a normal pneumococcal antibody response within the IgA
      and/or IgG2 subclass, and thus could be classified as true responders, while 15
      patients did not respond in either the IgA class or in the IgG2 subclass. When
      analysing differences between the responder (n = 11) and nonresponder (n = 15)
      groups, the latter demonstrated higher frequencies of respiratory tract
      infections and more severe lung pathology, as revealed by the presence of more
      bronchi visualised in the peripheral third of the lung by high-resolution
      computed tomography scanning. Moreover, nonresponders needed extensive lung
      surgery more often in order to control their disease (number of resected segments
      eight versus five). In conclusion, an important fraction of patients presenting
      with idiopathic bronchiectasis is associated with a selective anti-polysaccharide
      response deficiency and this subgroup appears to represent a more severe clinical
      phenotype. Therefore, it can be regarded as a separate clinical entity with
      possible therapeutic targets. In order to identify IgA and IgG2 anti
      polysaccharide nonresponders, all patients presenting with bronchiectasis of
      unknown aetiology should be immunised with a pneumococcal polysaccharide vaccine,
      and IgA and IgG2 isotype responses should be evaluated as well as the total
      antibody response.

PMID- 15738293
TI  - Azithromycin in bronchiolitis obliterans complicating bone marrow
      transplantation: a preliminary study.
AB  - Bronchiolitis obliterans (BO) is a serious noninfectious pulmonary complication
      following allogeneic bone marrow transplantation (BMT). Azithromycin, a macrolide
      antibiotic, may have a beneficial effect in BO through its anti-inflammatory
      effect. The aim of the current study was to investigate the potential effect of
      azithromycin on pulmonary function tests (PFTs) in BO complicating BMT. PFTs of
      153 post-BMT patients were followed; eight patients out of 153 (12%) developed
      obstructive airway disease on their PFTs, along with characteristic findings of
      BO on high-resolution computed tomography of the chest. These patients were given
      azithromycin 500 mg q.d. for 3 days, followed by 250 mg three times a week for 12
      weeks. Clinically significant improvements were achieved both in forced vital
      capacity, where the mean (95% confidence interval) increase reported was 410 mL
      (0.16-0.65), which was an average improvement of 21.57%, and in the forced
      expiratory volume in one second, where the mean increase noticed was 280 mL (0.10
      0.44), which was an average improvement of 20.58%. In conclusion, the potential
      role of azithromycin in the treatment of bronchiolitis obliterans is intriguing
      and it warrants further testing.

PMID- 15738294
TI  - Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung
      transplantation.
AB  - Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung
      transplantation (LTX). In a retrospective cohort study 12 stable healthy
      recipients (non-BOS) and eight patients with BOS were enrolled after LTX and
      matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in
      bronchoalveolar lavage (BAL) samples (n = 145) were analysed. BALs from patients
      with BOS were further divided according to whether they were obtained before (pre
      BOS) or after manifestation of BOS (BOS group). The MMP-9/TIMP-1 ratio was
      significantly increased in the BOS group compared with non-BOS or pre-BOS;
      furthermore, the ratio was negatively correlated with forced expiratory volume in
      one second. In zymography, the active form of MMP-9 was detected predominantly in
      the BOS group. In addition, zymography showed the banding pattern of neutrophil
      derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main
      source of MMP-9. According to that, MMP-9 was significantly correlated with the
      number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly
      with PMN. This is the first study to evaluate the expression of matrix
      metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time
      during manifestation of a fibroproliferative lung disease in patients. It
      demonstrates development of bronchiolitis obliterans syndrome after lung
      transplantation is associated with an imbalance of matrix metalloproteinases
      9/tissue inhibitors of metalloproteinase-1 ratio.

PMID- 15738295
TI  - Bosentan therapy for portopulmonary hypertension.
AB  - The dual endothelin receptor antagonist bosentan has been approved in several
      countries for pulmonary arterial hypertension, and patients with portopulmonary
      hypertension (PPHTN) have not specifically been excluded. However, no data have
      been published on the efficacy and safety of bosentan in this patient population.
      Here, the first clinical experiences with bosentan in patients with Child A
      cirrhosis and severe PPHTN are reported. In total, 11 consecutive patients with
      cirrhosis and severe PPHTN in New York Heart Association Functional Classes III
      and IV were treated for >1 yr with bosentan. After 1 yr of treatment with
      bosentan, all patients showed improved symptoms and exercise capacity. The 6-min
      walking distance increased from 310+/-102 m at baseline to 388+/-81 m at 1 yr.
      Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen
      uptake, from 12.6+/-3.5 to 16.6+/-2.8 mL.min(-1).kg(-1). Pulmonary vascular
      resistance fell from 944+/-519 to 635+/-321 dynes.s.L(-1). The medication was
      well tolerated by all patients, and there was no evidence of drug-related liver
      injury. In conclusion, bosentan proved to be efficacious and safe in a small
      number of patients with portopulmonary hypertension.

PMID- 15738296
TI  - N-terminal-pro-brain natriuretic peptide as a haemodynamic marker in idiopathic
      pulmonary arterial hypertension.
AB  - Patients with idiopathic pulmonary arterial hypertension usually undergo acute
      vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and
      therapeutical planning. The aim of this study was to evaluate the link between
      the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and
      haemodynamic parameters during the acute vasodilator test. A total of 22
      idiopathic pulmonary arterial hypertension patients who underwent acute
      vasodilator tests were studied. Blood samples were collected at baseline and
      after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each
      sample. A receiver-operating characteristic curve was used to evaluate the
      capability of the NT-pro-BNP level variation during NO inhalation in recognising
      nonresponders. To distinguish responders from nonresponders, the increase of the
      NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100%
      sensitivity (positive predictive value of 38% and a negative predictive value of
      100%). These results suggest that N-terminal-pro-brain natriuretic peptide was
      able to distinguish nonresponder patients with the acute vasodilator test. N
      terminal-pro-brain natriuretic peptide may be an interesting additional
      biological tool in the evaluation of idiopathic pulmonary arterial hypertension
      patients.

PMID- 15738297
TI  - All-cause mortality in males with sleep apnoea syndrome: declining mortality
      rates with age.
AB  - The objective of this study was to assess whether an increasing severity of sleep
      apnoea is associated with increased all-cause mortality hazards and to assess
      whether the syndrome is associated with excess mortality, in comparison with the
      general population. Participants included 14,589 adult males, aged 20-93 yrs,
      referred to the sleep clinics with suspected sleep apnoea or diagnosed with sleep
      apnoea. Altogether, 372 deaths were recorded after a median follow-up of 4.6 yrs.
      The crude all-cause mortality rate was 5.55/1,000 patient yrs, increasing with
      apnoea severity. Cox proportional analysis revealed that both respiratory
      disturbance index (RDI) and body mass index significantly influenced all-cause
      mortality hazard but there was no interaction between them. Males with
      respiratory disturbance index >30 had a significantly higher mortality hazard
      rate than the reference group of males with RDI < or =10. Comparing mortality
      rates of males with moderate/severe sleep apnoea to the general population
      revealed that only males aged <50 yrs showed an excess mortality rate. The hazard
      of mortality in sleep apnoea increases with apnoea severity as indexed by
      respiratory disturbance index. Moderate and severe levels of sleep apnoea are
      moderately associated with an increased risk of all-cause mortality, in
      comparison with the general population, particularly in males aged <50 yrs. The
      lack of information about possible confounders and treatment effects should be
      taken into consideration in the interpretation of these results.

PMID- 15738298
TI  - Effect of treating severe nasal obstruction on the severity of obstructive sleep
      apnoea.
AB  - An association between mouth breathing during sleep and increased propensity for
      upper airway collapse is well documented, but the effect of treatment for nasal
      obstruction on mouth breathing during sleep and simultaneous obstructive sleep
      apnoea (OSA) severity has not been described previously. A randomised single
      blind placebo- and sham-controlled crossover study of treatment (topical
      decongestant and external dilator strip) for nasal obstruction was carried out in
      10 patients (nine males; mean+/-SEM 46+/-5 yrs) with nasal obstruction and OSA.
      All patients had normal acoustic pharyngometry. The effect of treatment on nasal
      resistance, mouth breathing during sleep and OSA severity was quantified.
      Treatment of nasal obstruction was associated with a dramatic and sustained
      reduction in nasal resistance and the oral fraction of ventilation during sleep
      (mean (95% confidence interval) absolute reduction in oral fraction 30% (12-49)).
      Improvements in sleep architecture were observed during active treatment, and
      there was a modest reduction in OSA severity (change in apnoea-hypopnoea index 12
      (3-22)). In conclusion, treating nasal obstruction reduced mouth breathing during
      sleep and obstructive sleep apnoea severity, but did not effectively alleviate
      obstructive sleep apnoea.

PMID- 15738299
TI  - Cyclophosphamide and low-dose prednisolone in idiopathic pulmonary fibrosis and
      fibrosing nonspecific interstitial pneumonia.
AB  - The present study compared the efficacy of cyclophosphamide combined with low
      dose prednisolone in the treatment of idiopathic pulmonary fibrosis (IPF) with
      efficacy in idiopathic fibrosing nonspecific interstitial pneumonia fibrosing
      (NSIP). A total of 27 patients with IPF and 12 patients with fibrosing NSIP were
      included in this study. All patients had undergone surgical lung biopsy. The
      diagnoses were made based on clinical, radiological and pathological findings.
      All patients were treated with intermittent pulse therapy with methylprednisolone
      for 4 weeks, followed by cyclophosphamide with low-dose prednisolone. According
      to pulmonary function tests, four of 27 patients with IPF had improved, 22
      remained unchanged, and one had worsened at the completion of pulse therapy.
      After 1 yr of combination therapy, four of 27 patients had improved, 14 remained
      unchanged, and nine had worsened. After pulse therapy, four of 12 patients with
      fibrosing NSIP had improved, and eight remained unchanged. After 1 yr of
      combination therapy, eight of 12 patients had improved, four remained unchanged,
      and none had worsened. Median survival of IPF patients was 4.1 yrs, which is
      significantly worse than that of fibrosing NSIP patients. In conclusion, patients
      with fibrosing nonspecific interstitial pneumonia had a more favourable response
      to combination therapy and a better survival than those with idiopathic pulmonary
      fibrosis.

PMID- 15738300
TI  - Prone position reduces lung stress and strain in severe acute respiratory
      distress syndrome.
AB  - The present authors hypothesised that in severe acute respiratory distress
      syndrome (ARDS), pronation may reduce ventilator-induced overall stress (i.e.
      transpulmonary pressure (P(L))) and strain of lung parenchyma (i.e. tidal volume
      (V(T))/end-expiratory lung volume (EELV) ratio), which constitute major
      ventilator-induced lung injury determinants. The authors sought to determine
      whether potential pronation benefits are maintained in post-prone semirecumbent
      (SR(PP)) posture under pressure-volume curve-dependent optimisation of positive
      end-expiratory pressure (PEEP). A total of 10 anesthetised/paralysed,
      mechanically ventilated (V(T) = 9.0+/-0.9 mL.kg(-1) predicted body weight; flow =
      0.91+/-0.04 L.s(-1); PEEP = 9.4+/-1.3 cmH(2)O) patients with early/severe ARDS
      were studied in pre-prone semirecumbent (SR(BAS)), prone, and SR(PP) positions.
      Partitioned respiratory mechanics were determined during iso-flow (0.91 L.s(-1))
      experiments (V(T) varied within 0.2-1.0 L), along with haemodynamics, gas
      exchange, and EELV. Compared with SR(BAS), pronation/SR(PP) resulted in reduced
      peak/plateau P(L) at V(T)s> or =0.6 L; static lung elastance and additional lung
      resistance decreased and chest wall elastance (in prone position) increased; EELV
      increased (23-33%); V(T)/EELV decreased (27-33%); arterial oxygen
      tension/inspiratory oxygen fraction and arterial carbon dioxide tension improved
      (21-43/10-14%, respectively), and shunt fraction/physiological dead space
      decreased (21-50/20-47%, respectively). In early/severe acute respiratory
      distress syndrome, pronation under positive end-expiratory pressure optimisation
      may reduce ventilator-induced lung injury risk. Pronation benefits may be
      maintained in post-prone semirecumbent position.

PMID- 15738301
TI  - Identification of individuals susceptible to high-altitude pulmonary oedema at
      low altitude.
AB  - Individuals susceptible to high-altitude pulmonary oedema (HAPE) are
      characterised by an abnormal increase of pulmonary artery systolic pressure
      (PASP) in hypoxia and during normoxic exercise, reduced hypoxic ventilatory
      response, and smaller lung volume. In 37 mountaineers with well-documented
      altitude tolerance, it was investigated whether any combination of these
      noninvasive measurements, including exercise in hypoxia, could improve the
      identification of HAPE-susceptible subjects at low altitude. HAPE-susceptible
      subjects showed a significant higher increase of PASP during hypoxia at rest
      (48+/-10 mmHg) compared with controls (38+/-3 mmHg), as well as during normoxic
      exercise (57+/-14 versus 38+/-7 mmHg) and hypoxic exercise (69+/-13 versus 49+/-8
      mmHg). PASP could not be assessed in three and eight subjects during normoxic or
      hypoxic exercise, respectively, due to insufficient Doppler profiles or systemic
      arterial hypertension. Sensitivity (77-94%) and specificity (76-93%) were not
      significantly different between the various testing conditions. Additional
      assessment of hypoxic ventilatory response and lung function parameters did not
      improve identification of HAPE-susceptible subjects in a multivariate analysis.
      Due to the greater number of missing values in pulmonary artery systolic pressure
      measurements during hypoxic exercise, it was concluded that pulmonary artery
      systolic pressure measurements at rest during hypoxia or exercise in normoxia are
      most feasible for the identification of high-altitude pulmonary oedema
      susceptible subjects.

PMID- 15738302
TI  - Histone acetylation and deacetylation: importance in inflammatory lung diseases.
AB  - Inflammatory lung diseases are characterised by increased expression of multiple
      inflammatory genes that are regulated by proinflammatory transcription factors,
      such as nuclear factor-kappa B. Gene expression is regulated by acetylation of
      core histones through the action of coactivators, such as CREB-binding protein,
      with intrinsic histone acetyltransferase (HAT) activity. Conversely, gene
      repression is mediated via histone deacetylases (HDACs) and other corepressors.
      In asthma, there is an increase in HAT activity and some reduction in HDAC
      activity, which is restored by corticosteroid therapy. Corticosteroids switch off
      inflammatory genes in asthma through the inhibition of HAT activity and by the
      recruitment of HDAC2 to the activated inflammatory gene complex. In chronic
      obstructive pulmonary disease, there is a reduction in HDAC2 activity and
      expression, which may account for the amplified inflammation and resistance to
      the actions of corticosteroids. The reduction in HDAC2 may be secondary to
      oxidative and nitrative stress as a result of cigarette smoking and severe
      inflammation, and may also occur in severe asthma, smoking asthmatic patients and
      cystic fibrosis. Similar mechanisms may also account for the steroid resistance
      seen with latent adenovirus infections. The reduction in histone deacetylase
      activity can be restored by theophylline, which may be able to reverse steroid
      resistance in chronic obstructive pulmonary disease and other inflammatory
      diseases.

PMID- 15738303
TI  - Drug-susceptibility testing in tuberculosis: methods and reliability of results.
AB  - The demand for reliable drug-susceptibility testing (DST) increases with the
      expansion of antituberculosis drug-resistance surveillance, and with the need for
      an appropriate treatment of multidrug-resistant tuberculosis, whose incidence
      gradually increases in many parts of the world. However, the reliability of DST
      results obtained through widely used methods does not meet acceptable levels,
      except for DST to isoniazid and rifampicin. In general, susceptibility results
      are highly predictable, while resistance results show low predictive values when
      the resistance prevalence is <10%. Poor reliability stems from a weak correlation
      with clinical response and a low reproducibility due to the poor standardisation
      of the complex and fragile test procedures. Therefore, in vitro criteria of
      resistance for susceptibility testing should be carefully determined with
      representative clinical samples of Mycobacterium tuberculosis isolated from
      patients never treated with any antituberculosis drug, and from patients having
      failed treatment with a regimen containing the tested drug; DST should then be
      carefully standardised to obtain reproducible results. The critical concentration
      of some drugs is close to the minimal inhibitory concentration for wild
      susceptible strains and, thus, drug-susceptibility testing is prone to yield
      poorly reproducible results. These issues call for physicians' attention when
      using the results from drug-susceptibility testing for case management.

PMID- 15738304
TI  - Evolution of previous sarcoidosis under type 1 interferons given for severe
      associated disease.
AB  - Sarcoidosis is a granulomatous disorder with a well-known T helper (Th) type 1
      cell commitment and a key pathogenic role of interferon (IFN)-gamma. However,
      little is known about the influence of type 1 IFNs, such as IFN-alpha and IFN
      beta, on the course of previous sarcoidosis. The aim of this study was to
      determine whether type 1 IFNs can safely be used in patients with sarcoidosis for
      severe associated disease. The present study examined a series of four patients
      with sarcoidosis, treated by IFN-alpha or IFN-beta for viral hepatitis (three
      cases) or multiple sclerosis (one case). IFN was initiated soon after apparent
      recovery (three cases) or during a worsening phase of sarcoidosis (one case).
      Hydroxychloroquine was added in the case with active disease. Patients received
      interferon for 6-24 months and had close monitoring during and after IFN therapy.
      Interestingly, no recurrence or exacerbation of sarcoidosis had occurred at 4 yrs
      of follow up. Two patients were cured from viral hepatitis, whilst treatment for
      another failed. No neurological progression was observed in the remaining
      patient. This series suggests that, despite the T helper type 1 phenotype of
      sarcoid granulomatous reaction, type 1 interferons do not exacerbate sarcoidosis
      in remission and this makes their use possible if indicated. However, their
      effect in persistent forms of the disease needs further evaluation.

PMID- 15738306
TI  - Perception of what?

PMID- 15738305
TI  - Spontaneous pneumothorax in a 24-year-old female.

PMID- 15738307
TI  - Respiratory medicine: what is the diagnosis?

PMID- 15738310
TI  - Identification and characterization of PDE4A11, a novel, widely expressed long
      isoform encoded by the human PDE4A cAMP phosphodiesterase gene.
AB  - PDE4A11 is a novel cAMP-specific phosphodiesterase that is conserved in humans,
      mouse, rat, pig, and bat. Exon-1(4A11) encodes its unique, 81 amino acid N
      terminal region. Reverse-transcriptase polymerase chain reaction performed across
      the splice junction, plus identification of expressed sequence tags, identifies
      PDE4A11 as a long isoform possessing UCR1 and UCR2 regulatory domains. Transcript
      analysis shows that PDE4A11 is widely expressed compared with PDE4A10 and PDE4A4B
      long isoforms. Truncation analysis identifies a putative promoter in a 250-base
      pair region located immediately upstream of the start site in Exon-1(4A11).
      Recombinant PDE4A11, expressed in COS-7 cells, is a 126-kDa protein localized
      predominantly around the nucleus and in membrane ruffles. PDE4A11 exhibits a K(m)
      for cAMP hydrolysis of 4 microM, with relative V(max) similar to that of PDE4A10
      and PDE4A4B. PDE4A11 is dose-dependently inhibited by rolipram, 4-[(3-butoxy-4
      methoxyphenyl)-methyl]-2-imidazolidinone (Ro 20-1724), cilomilast, roflumilast,
      and denbufylline, with IC(50) values of 0.7, 0.9, 0.03, 0.004, and 0.3 microM,
      respectively. Soluble and particulate PDE4A11 exhibit distinct rates of thermal
      inactivation (55 degrees C; T((0.5)) = 2.5 and 4.4 min, respectively). Elevating
      cAMP levels in COS-7 cells activates PDE4A11 concomitant with its phosphorylation
      at Ser119 by protein kinase A (PKA). PDE4A11 differs from PDE4A4 in sensitivity
      to cleavage by caspase-3, interaction with LYN SH3 domain, redistribution upon
      long-term rolipram challenge, and sensitivity to certain PDE4 inhibitors.
      PDE4A11, PDE4A10, and PDE4A4 all can interact with betaarrestin. PDE4A11 is a
      novel, widely expressed long isoform that is activated by PKA phosphorylation and
      shows a distinct intracellular localization, indicating that it may contribute to
      compartmentalized cAMP signaling in cells in which it is expressed.

PMID- 15738311
TI  - Farnesyltransferase inhibitor BMS-214662 induces apoptosis in myeloma cells
      through PUMA up-regulation, Bax and Bak activation, and Mcl-1 elimination.
AB  - We have studied the mechanism of apoptosis elicited by the farnesyltransferase
      inhibitor (R)-7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3
      (phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662) in human
      myeloma cell lines. Low concentrations of BMS-214662 efficiently inhibited
      protein farnesylation but did not affect the activation of Akt. BMS-214662
      treatment increased levels of the BH3-only protein PUMA; induced proapoptotic
      conformational changes of Bax and Bak; reduced Mcl-1 levels; caused mitochondrial
      transmembrane potential loss; induced cytochrome c release, caspase activation,
      apoptosis-inducing factor (AIF) nuclear translocation, and phosphatidylserine
      exposure; and allowed the development of apoptotic morphology. Western blot
      analysis of cell extracts revealed the activation of caspases 2, 3, 8, and 9 upon
      treatment with BMS-214662. The general caspase inhibitor Z-VAD-fmk significantly
      prevented BMS-214662-induced death in U266 and RPMI 8226 cells but not in NCI
      H929 cells. A mixture of selective caspase inhibitors for caspases 9 [N
      benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethyl ketone (Z-LEHD-fmk)], 3 (Z-DEVD
      fmk), and 6 (Z-VEID-fmk) approached the protective effect of Z-VAD upon cell
      death. However, Z-VAD-fmk did not prevent BMS-214662-induced Bax and Bak
      activation and decrease of Mcl-1 levels. According to its effect on cell death, Z
      VAD-fmk inhibited nuclear translocation of AIF in RPMI 8226 and U266 but not in
      NCI-H929 cells. These results suggest that apoptosis triggered by BMS-214662 is
      initiated by a PUMA/Bax/Bak/Mcl-1-dependent mechanism. In some cell lines,
      Bax/Bak activation is not sufficient per se to induce mitochondrial failure and
      release of apoptogenic proteins, and so caspases need to be activated to
      facilitate apoptosis. After DeltaPsi(m) loss, execution of apoptosis was
      performed in all cases by a cytochrome c-enabled, caspase-9-triggered, caspase
      cascade and the nuclear action of AIF.

PMID- 15738312
TI  - Drug-use patterns among men who have sex with men presenting for alcohol
      treatment: differences in ethnic and sexual identity.
AB  - Two important gaps in our current understanding of drug and alcohol use among men
      who have sex with men (MSM) are that, first, little is known about the extent of
      drug- and alcohol-use disorders among MSM and, second, how these may vary among
      MSM who differ by ethnic/racial or sexual identity. This article is a descriptive
      study of the alcohol- and drug-use patterns and alcohol and drug diagnoses in an
      ethnically and sexually diverse sample of treatment-seeking MSM whose primary
      diagnosis is either alcohol abuse or alcohol dependence. The severity of alcohol
      problems did not vary by either ethnic or sexual identity, although the types of
      drugs that were used by participants did. African Americans reported a
      significantly higher number of drinks per drinking day compared with those in the
      other ethnic categories.Gay-identified men and those identified as either non
      Hispanic Whites or Hispanic/Latino were significantly more likely to have used
      stimulant drugs (amphetamine or methamphetamine) in the past 6 months, and non
      Hispanic Whites were less likely to have used marijuana compared with the other
      ethnic groups. A very high rate of comorbidity of drug- and alcohol-use disorders
      was found in this sample of ethnically diverse MSM. These results have important
      implications for the design of effective treatment interventions.

PMID- 15738313
TI  - Methamphetamine-using HIV-positive men who have sex with men: correlates of
      polydrug use.
AB  - Methamphetamine use has become a major problem among communities of men having
      sex with men (MSM), where it has been associated with high-risk behaviors.
      Methamphetamine is often combined with other drugs that may increase its risks
      and adverse health consequences. To examine differences in background
      characteristics, HIVrisk behaviors, and psychosocial variables among polydrug
      using HIV-positive MSM, the researchers classified a sample of 261 HIV-positive,
      methamphetamine-using MSM into three user groups: (1) methamphetamine only; (2)
      methamphetamine, marijuana, and poppers (light polydrug users); and (3)
      methamphetamine and other drugs (e.g., cocaine, heroin, hallucinogens, and
      ketamine; heavy polydrug users). Only 5% reported using only methamphetamine
      during the past 2 months; 31% were classified as light polydrug users, and 64%
      were classified as heavy polydrug users. Heavy polydrug users were significantly
      younger than light polydrug users (35.6 vs. 38.4, P<.01) and reported using
      methamphetamine for significantly fewer years (10.3 vs. 14.2 years, P<.001), but
      did not differ in the amount and frequency of methamphetamine or alcohol
      consumed. Heavy polydrug users reported significantly more sex partners of HIV
      negative and unknown serostatus and had more unprotected sex with these partners.
      Heavy polydrug users had significantly higher scores on impulsivity and negative
      self-perceptions, as compared with those of light polydrug users. In this sample
      of HIV-positive MSM, most of those who used methamphetamine had a pattern of
      polydrug use. Heavy polydrug users reported significantly more high-risk sexual
      behaviors and tended toward higher levels of impulsivity than light polydrug
      users. The implications of these findings are two-fold: (1) Longitudinal research
      is needed to establish causal relationships among methamphetamine use,
      impulsivity, negative self-perceptions, and sexual risk behavior in this target
      population; (2) behavioral interventions should evaluate whether methamphetamine
      use and sexual risk behavior can be reduced by modifying impulsivity and negative
      self-perceptions.

PMID- 15738315
TI  - Sustained reductions in drug use and depression symptoms from treatment for drug
      abuse in methamphetamine-dependent gay and bisexual men.
AB  - Methamphetamine abusers often complain of feelings of depression that can
      complicate accurately diagnosing these individuals during treatments for
      methamphetamine abuse. This article presents an examination of temporal
      associations between documented methamphetamine use and reported ratings of
      depression among 162 gay and bisexual male methamphetamine abusers who
      participated in a 16-week randomized clinical trial of four behavioral therapies
      for methamphetamine abuse. Methamphetamine use was measured using thrice-weekly
      urine samples analyzed for drug metabolite. Self-reported depressive symptoms
      were collected weekly using the Beck Depression Inventory (BDI). At treatment
      entry, 73.2% of participants rated their depressive symptoms as mild or higher in
      severity (BDI>or=10), with 28.5% reporting BDI scores in the moderate to severe
      range (BDI>or=19). All participants reported significant decreases in depressive
      symptoms from baseline through the end of treatment, regardless of treatment
      condition, HIV status, or mood disorder diagnosis. A mixed regression model
      showed methamphetamine use for up to 5 days prior to the BDI score strongly
      predicted depressive symptoms (F1, 968=18.6, P<.0001), while BDI scores had no
      significant association with subsequent methamphetamine use. Findings show that
      behavioral methamphetamine abuse treatment yields reductions in methamphetamine
      use and concomitant depressive symptom ratings that are sustained to 1 year after
      treatment entry.

PMID- 15738314
TI  - Recruiting drug-using men who have sex with men into behavioral interventions: a
      two-stage approach.
AB  - Drug-using men who have sex with men (MSM) are at high risk of acquiring or
      transmitting HIV infection. Efforts to change behaviors in this population have
      been hampered by difficulties in recruiting drug-using MSM into behavioral
      interventions. This study sought to develop an effective strategy for recruiting
      drug-using MSM into behavioral interventions that consist of motivational
      interviewing alone or motivational interviewing plus contingency management. MSM
      were recruited through advertising and community outreach into groups to discuss
      party drugs, party burnout, and sexual behavior, with the intervention
      subsequently described and enrollment offered in the group setting. Many more
      eligible MSM responded to advertisements for the discussion groups than
      advertisements for the interventions, and 58% of those who participated in the
      discussion groups volunteered for counseling. Men who entered counseling reported
      high levels of drug use and sexual activity and were racially and ethnically
      diverse; only 35% were willing to accept drug treatment. Results demonstrate that
      a two-stage strategy in which drug-using MSM are first recruited into discussion
      groups before they are offered a behavioral intervention can be an effective way
      to induce voluntary acceptance of an intervention employing a behavioral risk
      reduction approach.

PMID- 15738316
TI  - Men's pathways to risky sexual behavior: role of co-occurring childhood sexual
      abuse, posttraumatic stress disorder, and depression histories.
AB  - Recent reports of sexually transmitted infection-rate increases among men
      indicate the need for renewed study of male sexual risk behavior to aid
      development of updated and novel risk reduction interventions. Men who have
      childhood sexual abuse (CSA) histories consistently report frequent sexual risk
      behavior. The objective of this sturdy is to explore whether posttraumatic stress
      disorder (PTSD) and depression are moderators and/or mediators of the association
      between CSA and sexual risk in adult men. A cross-sectional survey study
      employing random digit dial recruitment was administered to men aged 18-49 years
      from Philadelphia County. Two hundred ninety eight men were recruited and
      screened for CSA history, administered items from the Posttraumatic Stress
      Diagnostic Scale (PDS) and Center for Epidemiologic Studies- Depression (CES-D),
      and asked to estimate their number of lifetime sexual partners (LSPs). Effects of
      sociodemographic characteristics, CSA, PTSD, and depression on the number of LSPs
      were modeled using Poisson regression. Results show that 197 (66%) men
      participated; 43 (22%) had CSA histories. CSA was significantly associated with
      PTSD/depression (P=.03). Four sociodemographic variables (age, race, sexual
      identity, and education), CSA (incidence rate ratio, IRR=1.47, P<.001), PTSD
      (IRR=1.19, P=.04), depression (IRR=1.29, P=.001), all 2-way interactions, and the
      3-way CSA/PTSD/depression interaction (IRR=11.00, P<.001) were associated with
      the number of LSPs (R2=0.27). In conclusion, sexual partnership patterns unique
      to men with CSA histories and comorbid PTSD/depression appear to lead to
      substantially higher numbers of LSPs. Estimates of this relationship may have
      been biased toward the null by underreporting that can occur with phone surveys.
      Cross-sectional studies do not support causal inferences; however, the
      identification of a moderating and mediating influence of PTSD/depression on the
      relationship between CSA and sexual risk behavior is important and suggests the
      need for future studies with larger samples that examine trajectories for CSA,
      psychiatric illness, and sexual partnerships.

PMID- 15738317
TI  - Surfing new territory: club-drug use and risky sex among Hispanic men who have
      sex with men recruited on the Internet.
AB  - The Internet presents unique and growing opportunities for conducting HIV/ STD
      research. This article reports on the first 171 participants enrolled in an
      ongoing study examining use of the Internet to recruit Hispanic men who have sex
      with men (HMSM) living in an AIDS epicenter to participate in community-based
      studies. First, it describes initial success with chatroom recruitment. Second,
      it compares the demographic, psychosocial, and sexual risk practices among HMSM
      recruited through the Internet who had used club drugs in the last 6 months and
      those who had not. In 2 months, 211 hours were spent recruiting in chatrooms; 735
      chatroom users were engaged. Researchers used a scripted dialogue to describe the
      study and to invite chatroom users to visit the study's community sites for
      screening and enrollment. One hundred and seventy-six men came to the community
      sites; 172 (98%) were eligible and completed an audio-computer assisted self
      interview. In the last 6 months, 48.5% of the sample had used club drugs [defined
      as cocaine, crystal methamphetamines (crystal), amyl nitrites (poppers), Ecstasy,
      gamma-hydroxybutyrate (GHB), ketamine (Special K), and Viagra]. The proportion of
      men reporting use of each drug was: cocaine (15.8%), crystal (11.7%), poppers
      (31.6%), Ecstasy (14%), GHB (3.5%), Special K (3.5%), and Viagra (19.3%). In
      multivariate analyses, having higher number of sex partners, having higher social
      isolation scores, and having engaged in unprotected receptive anal intercourse
      were significantly associated with club-drug use. These initial findings suggest
      that high-risk HMSM can be successfully recruited through chatroom dialogues to
      participate in community-based HIV studies. The alarmingly high rates of club
      drug use and risky sexual practices among HMSM underscore the need for effective
      HIV preventive interventions for this population.

PMID- 15738318
TI  - Reasons for stimulant use among Latino gay men in San Francisco: a comparison
      between methamphetamine and cocaine users.
AB  - The literature on drug-using gay men has documented a strong relationship between
      methamphetamine (MA) use and high-risk sexual practices. Of particular concern is
      that MA use is associated with powerful sexual effects that may facilitate the
      transmission of HIV. As a group, Latino gay men show high risk for HIV infection,
      and such risk has been related to episodes of sex under the influence of drugs.
      However, little information exists about stimulant use among Latino gay men, and
      it is not known whether MA use in this population is similarly motivated by
      sexual effects. This study reports reasons for stimulant use in a sample of 300
      Latino gay men randomly selected from social and sexual venues; only men who
      reported stimulant use in the last 6 months were included in the study. Of
      stimulant users, 51% (n=153) reported MA, 44% (n=133) reported cocaine, and 5%
      (n=14) reported crack as their "most frequently used stimulant" (MFS); reasons
      for use were assessed for the participant's specific MFS. Reasons for stimulant
      use clustered by five main factors, including energy, sexual enhancement, social
      connection, coping with stressors, and focused work productivity. MA users gave
      reasons more frequently related to sexual enhancement (to have better sex, more
      sex, and more anal sex) whereas cocaine users gave reasons more often related to
      social connections (to be more sociable and to fit in with other gay men). These
      findings suggest that Latino gay men use stimulants for reasons that are
      important in their social, emotional, work, and sexual lives. Like non-Latino
      Whites, Latino gay men were found to rely on MA for reasons related to sexual
      enhancement, possibly to meet cultural expectations and norms of sexual prowess
      and sexual success in the gay community.

PMID- 15738319
TI  - Longitudinal patterns of methamphetamine, popper (amyl nitrite), and cocaine use
      and high-risk sexual behavior among a cohort of san francisco men who have sex
      with men.
AB  - Most prior studies examining drug use among men who have sex with men (MSM) have
      been cross-sectional or retrospective and have not determined whether periods of
      increased drug use are associated with high-risk sexual behavior at the
      individual level. In this article, we describe patterns of use of
      methamphetamines, poppers, and sniffed cocaine and sexual risk behavior among 736
      San Francisco MSM enrolled in the EXPLORE study and followed for up to 48 months.
      In longitudinal analysis, use of methamphetamines, poppers, and sniffed cocaine
      declined during follow-up. However, compared with older participants, younger
      participants were more likely to increase their drug use over time. Results of
      conditional logistic regression demonstrated that high-risk sexual behavior was
      more common during reporting periods characterized by increased methamphetamine,
      poppers, or sniffed cocaine use. This within-person analysis found that compared
      with periods of no drug use, periods of both light drug use (less than weekly use
      of drugs) and heavier drug use (at least weekly use of at least one drug) were
      significantly associated with increased risk of engaging in unprotected anal sex
      with an HIV-positive or unknown-status partner. These results suggest that even
      intermittent, recreational use of these drugs may lead to high-risk sexual
      behavior, and that, to reduce and prevent risks of HIV, no level of use of these
      drugs should be considered "safe." HIV prevention interventions should target MSM
      who report either light or heavy use of methamphetamines, poppers, and sniffed
      cocaine.

PMID- 15738320
TI  - A comparison of HIV seropositive and seronegative young adult heroin- and cocaine
      using men who have sex with men in New York City, 2000-2003.
AB  - The purpose of this analysis was to determine the prevalence and correlates of
      HIV infection among a street-recruited sample of heroin- and cocaine-using men
      who have sex with men (MSM). Injection (injecting <or=3 years) and non-injection
      drug users (heroin, crack, and/or cocaine use <10 years) between 18 and 40 years
      of age were simultaneously street-recruited into two cohort studies in New York
      City, 2000-2003, by using identical recruitment techniques. Baseline data
      collected among young adult men who either identified as gay/bisexual or reported
      ever having sex with a man were used for this analysis. Nonparametric statistics
      guided interpretation. Of 95 heroin/ cocaine-using MSM, 25.3% tested HIV
      seropositive with 75% reporting a previous HIV diagnosis. The majority was black
      (46%) or Hispanic (44%), and the median age was 28 years (range 18-40). HIV
      seropositive MSM were more likely than seronegatives to be older and to have an
      HIV-seropositive partner but less likely to report current homelessness, illegal
      income, heterosexual identity, multiple sex partners, female partners, and sex
      for money/drug partners than seronegatives. These data indicate high HIV
      prevalence among street-recruited, drug-using MSM compared with other injection
      drug use (IDU) subgroups and drug-using MSM; however, lower risk behaviors were
      found among HIV seropositives compared with seronegatives. Large-scale studies
      among illicit drug-using MSM from more marginalized neighborhoods are warranted.

PMID- 15738321
TI  - HIV prevalence and risk behaviors among men who have sex with men and inject
      drugs in San Francisco.
AB  - The dual risks of male-to-male sex and drug injection have put men who have sex
      with men and inject drugs (MSM-IDU) at the forefront of the HIV epidemic, with
      the highest rates of infection among any risk group in the United.States. This
      study analyzes data collected from 357 MSM-IDU in San Francisco between 1998 and
      2002 to examine how risk behaviors differ by HIV serostatus and self-identified
      sexual orientation and to assess medical and social service utilization among HIV
      positive MSM-IDU. Twenty-eight percent of the sample tested HIV antibody
      positive. There was little difference in risk behaviors between HIV-negative and
      HIV-positive MSM-IDU. Thirty percent of HIV-positive MSM-IDU reported
      distributive syringe sharing, compared to 40% of HIV negatives. Among MSM-IDU who
      reported anal intercourse in past 6 months, 70% of positives and 66% of HIV
      negatives reported unprotected anal intercourse. HIV status varied greatly by
      self-identified sexual orientation: 46% among gay, 24% among bisexual, and 14%
      among heterosexual MSM-IDU. Heterosexual MSM-IDU were more likely than other MSM
      IDU to be homeless and to trade sex for money or drugs. Gay MSM-IDU were more
      likely to have anal intercourse. Bisexual MSM-IDU were as likely as heterosexual
      MSM-IDU to have sex with women and as likely as gay-identified MSM-IDU to have
      anal intercourse. Among MSM-IDU who were HIV positive, 15% were currently on
      antiretroviral therapy and 18% were currently in drug treatment, and 87% reported
      using a syringe exchange program in the past 6 months. These findings have
      implications for the development of HIV interventions that target the diverse MSM
      IDU population.

PMID- 15738322
TI  - Spatial bridging in a network of drug-using male sex workers.
AB  - This study sought to determine whether drug-using male sex workers (MSWs)
      spatially bridge sexual networks across cities and to determine whether the
      behaviors of MSWs who bridge differ from the behaviors of those who do not. Data
      were collected from 42 MSWs in Houston, Texas, between May 2003 and February
      2004. Spatial bridging was defined as having traded sex for money in another city
      before traveling to and trading in Houston. Cities bridged by MSWs were
      geographically plotted and were primarily located in the Gulf Coast and in
      Florida. Slightly less than half of MSWs were identified as spatially bridging
      from one city to another. A significantly higher proportion of MSWs who bridged
      cities were homosexual (55% vs. 23%) and HIV positive (31% vs. 5%). Those who
      bridged cities used marijuana and injected drugs more frequently and had
      significantly more male sex partners than MSWs who did not bridge cities. Despite
      the small sample size, this study found that many drug-using MSWs spatially
      bridge sexual networks in cities where they trade sex for money.

PMID- 15738323
TI  - Sexual diversity among black men who have sex with men in an inner-city
      community.
AB  - Dramatic increases in HIV-incidence rates have been documented for Black men who
      have sex with men (MSM). Moreover, MSM has become a more visible HIV-transmission
      route in the Black community, in part due to public interest in the "down low"
      (i.e., "straight" men who also have sex with men). Interviews were conducted with
      21 Black MSM in central Brooklyn, New York City, in efforts to understand the
      diversity of MSM experience in a low income, high HIV-prevalence community. Two
      thirds of the men identified as either heterosexual (43%) or bisexual (24%) and
      15 (71%) MSM reported recent sex with women. Conformity to masculine social role
      expectations made it difficult to identify sex partners in the community;
      therefore, men relied on private sex clubs and the Internet. The findings suggest
      that stigma surrounding both HIV and homosexuality may effectively insure that
      nonheterosexual preferences and practices remain hidden in the Black community. A
      focus on sexual orientation and bisexuality has obscured the issue of race in the
      HIV/AIDS epidemic among Black MSM. In the long term, public health promotion and
      HIV prevention will require greater tolerance and acceptance of sexual diversity
      in the Black community.

PMID- 15738324
TI  - Longitudinal investigation of methamphetamine use among gay and bisexual men in
      New York City: findings from Project BUMPS.
AB  - In recent years, methamphetamine has become a drug more commonly used among gay
      and bisexual men in New York City. Part of a longitudinal investigation of drug
      abuse in this population involved assessing the patterns and context of
      methamphetamine use during the course of 1 year. Findings indicate that among
      self-identified club-drug-using men, methamphetamine is widely used by men across
      age groups, educational level, race/ethnicity, and HIV status. Participants
      reported use of methamphetamine in combination with numerous other illicit and
      prescribed substances and in a variety of contexts outside the "club scene."
      Reasons for and contexts of use are related to HIV status, with HIV-positive men
      indicating a greater likelihood of use to avoid conflict, unpleasant emotions,
      and social pressures, and reporting higher levels of use in environments such as
      bathhouses and "sex parties." These patterns and relationships are consistent
      across time and suggest a complex interaction between person level factors,
      environmental factors, and HIV. Findings indicate that treatment of
      methamphetamine addiction among gay and bisexual men must take into account the
      complex interrelationships between mental health, drug use, sexual risk taking,
      and HIV.

PMID- 15738326
TI  - Introduction: new dynamics of HIV risk among drug-using men who have sex with
      men.

PMID- 15738325
TI  - Drug and sexual risk in four men who have sex with men populations: evidence for
      a sustained HIV epidemic in New York City.
AB  - The objective of this article was to examine drug and sexual risk in four salient
      groups of men who have sex with men (MSM) in New York City (NYC): (1) nonhomeless
      young MSM (YMSM), (2) homeless YMSM, (3) adult MSM Speed users, and (4) HIV
      positive "POZ Party" MSM. Lifetime and current exposure to drugs, drug injection,
      and selected drug-sex interactions are highlighted in each group. Data derive
      from recently completed field-based, ethnoepidemiological studies that used venue
      oriented/targeted sampling and semistructured interviews. Across all four groups,
      findings show that both drug and sexual risk remain prevalent in the MSM
      population in NYC. This is especially troubling given the already high background
      prevalence of HIV and other sexually transmitted diseases in NYC and the
      widespread suffering and death already wrought by HIV/AIDS among MSM. These
      findings suggest that available public health interventions today are, in many
      respects, failing to reach, engage, and affect critical risk groups within the
      NYC MSM population.

PMID- 15738327
TI  - The concentration of substance use, criminal justice involvement, and HIV/AIDS in
      the families of drug offenders.
AB  - Substance use (SU), criminal justice involvement (CJI), and HIV/AIDS co-occur in
      many urban families, but little is known about their intergenerational prevalence
      and the impact of their conjunction on these families. We determined lifetime
      prevalence of SU, CJI, and HIV/AIDS in 62 families with a member (the index case)
      on parole or probation for a drug offense and enrolled in the direct service arm
      of Family Justice, La Bodega de La Familia--a community support program in New
      York City's Lower East Side. Among these families, index cases are 94% male, and
      97% Latino, with a median age of 37. Records of 80% of open cases, in months
      March through May, in 2003 (N = 62) were reviewed, and the family maps or
      "genograms," were analyzed and coded (by age, sex, and relationship to the index)
      to identify all significant members with histories of SU, CJI, and HIV/AIDS. Of
      the 62 families (with a total of 592 individuals) 82% had at least one other
      member besides the index case with a history of SU, 62% had two or more, and 40%
      had three or more; 72% had one other member with a history of CJI, 45% had two or
      more, and 24% had three or more. At least one member had HIV/AIDS in 49% of the
      families, 16% had two or more, and 10% had three or more. Of the 105 family
      members who reported a history of CJI, 88% had a history of substance use. These
      data demonstrate the extent to which many families in communities such as this
      are struggling with the burdens associated with having multiple relatives
      involved in the criminal justice system, largely related to drug use and
      frequently with HIV and AIDS. These data point to an important role for family
      focused interventions to ameliorate the consequences of high rates of familial
      drug use, incarceration and other forms of CJI, and HIV/AIDS.

PMID- 15738328
TI  - Cash benefits are associated with lower risk behavior among the homeless and
      marginally housed in San Francisco.
AB  - To address the widespread debate about the role of public assistance to the urban
      poor, the authors determined characteristics of individuals receiving cash
      assistance and explored the link between cash subsidies and risk behavior. From
      1999 to 2000, a representative sample of homeless and marginally housed (HMH)
      adults living in San Francisco was recruited and interviewed about subsidies,
      shelter, jail, and drug use. Among 1,156 adults, 87% were ever homeless, 22%
      currently injected drugs, and 14% were HIV positive. Sixty percent of
      participants reported that most of their income came from subsidies [mostly
      subsidized (MS)]. The MS had lower odds of receiving any income from selling
      drugs or trading sex. Adjusting for HIV infection, the MS had higher odds of
      sleeping in a hotel [odds ratio (OR) = 2.39] or shelter (OR = 1.61) compared to
      the street. The MS had lower odds of injection drug use (OR = 0.69) and recent
      incarceration (OR = O.77). Among San Francisco's homeless, being MS was
      positively associated with having shelter and negatively associated with
      injection drug use and incarceration. These data suggest that government
      subsidies are associated with positive health behaviors among the urban poor.

PMID- 15738330
TI  - Urban women's use of rural-based health care services: the case of Igbo women in
      Aba City, Nigeria.
AB  - This study addresses the quest for rural-based health care services among women
      in urban Nigeria relying on a large qualitative database obtained from 63 Igbo
      women living in Aba, Nigeria. Results indicate that urban Igbo women of different
      socioeconomic and demographic characteristics utilize the services of different
      rural-based health care providers-indigenous healers, traditional birth
      attendants (TBAs), faith/spiritual, western-trained doctors and nurses as well as
      chemist shopkeepers-for conditions ranging from infertility, through child
      birthing and abortions, to swollen body, epilepsy, bone setting, and stubborn
      skin diseases. Major attractions to rural-based therapists were the failure of
      urban-based health services to provide cure, perceived mystical nature of
      conditions, need to conceal information on therapeutic progress and/or the nature
      of specific disease conditions, belief in rural-based therapists' ability to cure
      condition, and affordability of the services of rural-based health care
      providers. Findings underscore the critical implications of service
      characteristics, cultural beliefs, and the symbolic content of place(s) for care
      seekers' patterns of resort. We suggest that need exists for policies and
      programs aimed at making health care services in urban Nigeria more responsive to
      care seekers' socioeconomic and cultural sensitivities, integrating informal
      health care providers into Nigeria's health care system, and strengthening public
      health education in Nigeria.

PMID- 15738329
TI  - Age differences in health effects of stressors and perceived control among urban
      African American women.
AB  - A conceptual model of the stress process has been useful in examining
      relationships among a variety of stressors, health status, and protective factors
      that modify the health-stress relationship. The model can contribute to an
      understanding of variations in health among people living in urban environments
      experiencing high degrees of stress. This study examines social contextual
      stressors in the neighborhood, health outcomes, and perceived control at multiple
      levels beyond the individual as a protective factor, among a random sample (N =
      679) of predominantly low-income African American women who reside on Detroit's
      east side. Findings suggest that although stress has a consistently negative
      impact on health, perceived control may buffer against the deleterious effects of
      stress. The buffering role of perceived control, however, depends on age, the
      type of stressor examined, and the context or level at which perceived control is
      assessed (e.g., organizational, neighborhood, beyond the neighborhood). For young
      women, perceived control was found to be health protective. Among older women,
      perceived control in the face of stressors was inversely related to health. These
      findings suggest the need for health and social service programs and policy
      change strategies to both increase the actual influence and control of women
      living in low-income urban communities and to reduce the specific social
      contextual stressors they experience.

PMID- 15738332
TI  - Where does walkability matter the most? An environmental justice interpretation
      of New Jersey data.
AB  - Physical inactivity contributes to a growing proportion of premature mortality
      and morbidity in the United States, and the last decade has been the focus of
      calls for action. Analysis of 340 residents of New Jersey found that 15%-20%
      reported multiple problems with using their immediate neighborhoods for physical
      activity. These respondents were disproportionately African Americans living in
      neighborhoods that they regard as only of fair or poor quality. Neighborhood
      walkability is a second-wave environmental justice issue meriting carefully
      designed research and ameliorative actions in concert with other neighborhood
      level redevelopment activities.

PMID- 15738331
TI  - Metropolitan income inequality and working-age mortality: a cross-sectional
      analysis using comparable data from five countries.
AB  - The relationship between income inequality and mortality has come into question
      as of late from many within-country studies. This article examines the
      relationship between income inequality and working-age mortality for metropolitan
      areas (MAs) in Australia, Canada, Great Britain, Sweden, and the United States to
      provide a fuller understanding of national contexts that produce associations
      between inequality and mortality. An ecological cross-sectional analysis of
      income inequality (as measured by median share of income) and working-age (25-64)
      mortality by using census and vital statistics data for 528 MAs (population
      >50,000) from five countries in 1990-1991 was used. When data from all countries
      were pooled, there was a significant relationship between income inequality and
      mortality in the 528 MAs studied. A hypothetical increase in the share of income
      to the poorest half of households of 1% was associated with a decline in working
      age mortality of over 21 deaths per 100,000. Within each country, however, a
      significant relationship between inequality and mortality was evident only for
      MAs in the United States and Great Britain. These two countries had the highest
      average levels of income inequality and the largest populations of the five
      countries studied. Although a strong ecological association was found between
      income inequality and mortality across the 528 MAs, an association between income
      inequality and mortality was evident only in within-country analyses for the two
      most unequal countries: the United States and Great Britain. The absence of an
      effect of metropolitan-scale income inequality on mortality in the more
      egalitarian countries of Canada, Australia, and Sweden is suggestive of national
      scale policies in these countries that buffer hypothetical effects of income
      inequality as a determinant of population health in industrialized economies.

PMID- 15738333
TI  - Asthma in Medicaid managed care enrollees residing in New York City: results from
      a post-World Trade Center disaster survey.
AB  - The collapse of the World Trade Center on September 11, 2001, released a
      substantial amount of respiratory irritants into the air. To assess the asthma
      status of Medicaid managed care enrollees who may have been exposed, the New York
      State Department of Health, Office of Managed Care, conducted a mail survey among
      enrollees residing in New York City. All enrollees, aged 5-56 with persistent
      asthma before September 11, 2001, were surveyed during summer 2002.
      Administrative health service utilization data from the Medicaid Encounter Data
      System were used to validate and supplement survey responses. A total of 3,664
      enrollees responded. Multivariate logistic regression models were developed to
      examine factors associated with self-reported worsened asthma post September 11,
      2001, and with emergency department/inpatient hospitalizations related to asthma
      from September 11, 2001, through December 31, 2001. Forty-five percent of survey
      respondents reported worsened asthma post 9/11. Respondents who reported worsened
      asthma were significantly more likely to have utilized health services for asthma
      than those who reported stable or improved asthma. Residence in both lower
      Manhattan (adjusted OR = 2.28) and Western Brooklyn (adjusted OR = 2.40) were
      associated with self-reported worsened asthma. However, only residents of Western
      Brooklyn had an elevated odds ratio for emergency department/inpatient
      hospitalizations with diagnoses of asthma post 9/11 (adjusted OR = 1.52).
      Worsened asthma was reported by a significant proportion of this low-income,
      largely minority population and was associated with the location of residence.
      Results from this study provide guidance to health care organizations in the
      development of plans to ensure the health of people with asthma during disaster
      situations.

PMID- 15738334
TI  - Use of medical counseling for the prevention and control of smoking in the
      municipality of old Havana.
AB  - Physicians have an important responsibility for addressing smoking cessation and
      prevention with their patients. The objective of this study was to describe the
      use of physician counseling for the prevention and control of smoking and to
      predict its use according to physician characteristics. A cross-sectional survey
      of a random sample of 121 family physicians in one municipality of the city of
      Havana was used to address sociodemographic factors, years of practice in the
      community, smoking status, use of physician counseling in daily practice (ask,
      advise, and assist), and the role of physician counseling as an intervention.
      Summary statistics were used as well as canonical and discriminant analyses. The
      prevalence of smoking among the physicians was 18%. The smoking status of
      patients was determined "almost always" by 32% of doctors. Twenty-five percent
      asked their patients whether they intended to stop smoking; 35% recommended
      smoking cessation; and 38% gave advice on how to achieve this. More than half
      (58%) explored factors that might influence cessation in their patients, and 12%
      reported doing this "frequently." Physician characteristics were associated
      significantly with preventive behavior, with community involvement, and with the
      perceived value of physician counseling and smoking status. Physician responses
      were associated with actual practice in 82% of the cases. Predisposing,
      facilitating, and reinforcing factors for preventive behavior were strong
      determinants of active involvement by physicians in daily practice. Training of
      health professionals must include smoking cessation.

PMID- 15738335
TI  - Smoking practices in New York City: the use of a population-based survey to guide
      policy-making and programming.
AB  - To inform New York City's (NYC's) tobacco control program, we identified the
      neighborhoods with the highest smoking rates, estimated the burden of second-hand
      smoke exposure, assessed the early response to state taxation, and examined
      cessation practices. We used a stratified random design to conduct a digit-dialed
      telephone survey in 2002 among 9,674 New York City adults. Our main outcome
      measures included prevalence of cigarette smoking, exposure to second-hand smoke,
      the response of smokers to state tax increases, and cessation practices. Even
      after controlling for sociodemographic factors (age, race/ethnicity, income,
      education, marital status, employment status, and foreign-born status) smoking
      rates were highest in Central Harlem and in the South Bronx. Sixteen percent of
      nonsmokers reported frequent exposure to second-hand smoke at home or in a
      workplace. Among smokers with a child with asthma, only 33% reported having a no
      smoking policy in their homes. More than one fifth of smokers reported reducing
      the number of cigarettes they smoked in response to the state tax increase. Of
      current smokers who tried to quit, 65% used no cessation aid. These data were
      used to inform New York City's smoke-free legislation, taxation, public
      education, and a free nicotine patch give-away program. In conclusion, large,
      local surveys can provide essential data to effectively advocate for, plan,
      implement, and evaluate a comprehensive tobacco control program.

PMID- 15738336
TI  - Alcohol, stress-related factors, and short-term absenteeism among urban transit
      operators.
AB  - Transit operators, relative to workers in many other occupations, experience high
      levels of work-related stress, as documented through neuroendocrine elevations on
      the job vis-a-vis resting states (J Occup Health Psychol. 1998;3:122-129).
      Previous research suggests that self-reported job stress is associated with
      higher levels of alcohol consumption among transit operators (Alcohol Clin Exp
      Res. 2000;24:1011-1019) and with absenteeism (Working Environment for Local
      Public Transport Personnel, Stockholm: Swedish Work Environmental Fund, 1982;
      Work Stress. 1990;4:83-89). The purpose of this study was to examine the
      interrelationships between alcohol use, stress-related factors (stressful life
      events, job stressors, and burnout), and short-term absenteeism among a
      multiethnic cohort of urban transit operators. Self-reported measures of alcohol,
      stress-related factors, and short-term absenteeism were obtained from a sample
      (n=1,446) of San Francisco municipal transit operators who participated in the
      1993-1995 Municipal Railway Health and Safety Study. Multivariate logistic
      regression analyses showed that absenteeism among drinkers was associated with
      risk for alcohol dependence [odds ratio (OR)=2.46, heavy drinking (OR=1.87),
      alcohol-related harm (OR=2.17), increased drinking since becoming a transit
      operator (OR=1.74), and having any problem drinking indicator (OR=1.72). The
      association between absenteeism and stress-related factors varied by gender and
      drinking status. Final multivariate models among drinkers indicated that among
      males, problem drinking (OR=1.82), stressful life events (OR=1.62), and job
      burnout (OR=1.22) were independently associated with elevated odds of
      absenteeism. Among female drinkers, only stressful life events (OR=5.17) was
      significantly associated with elevated odds of absenteeism. Findings suggest that
      workplace interventions that address both individual and environmental stressors
      are most likely to have a positive impact on health-related outcomes, including
      problem drinking, thereby reducing absenteeism.

PMID- 15738337
TI  - Steel dust in the New York City subway system as a source of manganese, chromium,
      and iron exposures for transit workers.
AB  - The United States Clean Air Act Amendments of 1990 reflected increasing concern
      about potential effects of low-level airborne metal exposure on a wide array of
      illnesses. Here we summarize results demonstrating that the New York City (NYC)
      subway system provides an important microenvironment for metal exposures for NYC
      commuters and subway workers and also describe an ongoing pilot study of NYC
      transit workers' exposure to steel dust. Results from the TEACH (Toxic Exposure
      Assessment, a Columbia and Harvard) study in 1999 of 41 high-school students
      strongly suggest that elevated levels of iron, manganese, and chromium in
      personal air samples were due to exposure to steel dust in the NYC subway.
      Airborne concentrations of these three metals associated with fine particulate
      matter were observed to be more than 100 times greater in the subway environment
      than in home indoor or outdoor settings in NYC. While there are currently no
      known health effects at the airborne levels observed in the subway system, the
      primary aim of the ongoing pilot study is to ascertain whether the levels of
      these metals in the subway air affect concentrations of these metals or related
      metabolites in the blood or urine of exposed transit workers, who due to their
      job activities could plausibly have appreciably higher exposures than typical
      commuters. The study design involves recruitment of 40 transit workers
      representing a large range in expected exposures to steel dust, the collection of
      personal air samples of fine particulate matter, and the collection of blood and
      urine samples from each monitored transit worker.

PMID- 15738338
TI  - Mass transit infrastructure and urban health.
AB  - Mass transit is a critical infrastructure of urban environments worldwide. The
      public uses it extensively, with roughly 9 billion mass transit trips occurring
      annually in the United States alone according to the U.S. Department of
      Transportation data. Its benefits per traveler include lower emissions of air
      pollutants and energy usage and high speeds and safety records relative to many
      other common modes of transportation that contribute to human health and safety.
      However, mass transit is vulnerable to intrusions that compromise its use and the
      realization of the important benefits it brings. These intrusions pertain to
      physical conditions, security, external environmental conditions, and equity. The
      state of the physical condition of transit facilities overall has been summarized
      in the low ratings the American Society of Civil Engineers gives to mass transit,
      and the large dollar estimates to maintain existing conditions as well as to
      bring on new improvements, which are, however, many times lower than investments
      estimated for roadways. Security has become a growing issue, and numerous
      incidents point to the potential for threats to security in the US. External
      environmental conditions, such as unexpected inundations of water and electric
      power outages also make transit vulnerable. Equity issues pose constraints on the
      use of transit by those who cannot access it. Transit has shown a remarkable
      ability to rebound after crises, most notably after the September 11, 2001
      attacks on the World Trade Center, due to a combination of design and operational
      features of the system. These experiences provide important lessons that must be
      captured to provide proactive approaches to managing and reducing the
      consequences of external factors that impinge negatively on transit.

PMID- 15738339
TI  - Health and safety hazards associated with subways: a review.
AB  - Subway systems are key components in mass transportation networks worldwide,
      providing rapid and affordable transportation to urban communities in 58
      different countries. The benefits afforded by subway transit are numerous and
      mainly derived from the reduction in automobile use, thereby limiting
      environmental and health hazards associated with exhaust-air emissions.
      Additionally, by limiting congestion and providing vital transportation links
      within a city, subways also improve the overall quality of life of urban
      communities. However, to best maximize the positive impact on the urban
      environment, subway systems need to provide a safe and healthy environment for
      both passengers and subway transit workers. Periodically, safety concerns are
      raised, most recently in relation to the vulnerability of subways to terrorist
      attacks. To examine this issue more carefully, we conducted a structured review
      of the literature to identify and characterize potential health and safety
      hazards associated with subways. A secondary goal was to identify various risk
      management strategies designed to minimize the risk of these hazards. This
      information may be helpful to urban communities, urban planners, public health
      specialists, and others interested in subway safety.

PMID- 15738340
TI  - Public transportation: advantages and challenges.

PMID- 15738341
TI  - The urban health "advantage".

PMID- 15738342
TI  - Cardiovascular and renal regulation by the angiotensin type 2 receptor: the AT2
      receptor comes of age.

PMID- 15738343
TI  - Management of hypertension in the setting of autonomic failure: a
      pathophysiological approach.
AB  - We discuss 2 cases presenting clinically with disabling orthostatic hypotension
      and severe supine hypertension. This is a common presentation of autonomic
      failure, and one that challenges conventional treatment. Clinical findings of
      isolated autonomic failure were the most prominent manifestation in case 1,
      whereas a movement disorder was the key finding in case 2. The differential
      diagnosis and treatment of orthostatic hypotension is discussed from a
      pathophysiological approach. Understanding of the underlying mechanisms of
      disorders of the autonomic nervous system is fundamental for an effective
      management of these patients and provides insight into more common disorders such
      as essential hypertension.

PMID- 15738344
TI  - Persistent sympathetic activation during chronic antihypertensive therapy: a
      potential mechanism for long term morbidity?
AB  - Previous studies have demonstrated that antihypertensive treatment resets
      baroreflex control of heart rate (HR) and increases cardiac vagal baroreflex
      sensitivity. However, it is uncertain whether baroreflex control of muscle
      sympathetic nerve activity (MSNA) also resets after treatment. We tested the
      hypothesis that chronic antihypertensive therapy alters baroreflex regulation of
      MSNA in patients with untreated moderate hypertension. Seven newly diagnosed
      patients with systolic blood pressure (BP) of 159+/-5 mm Hg (mean+/-SE) and
      diastolic BP of 103+/-4 mm Hg were studied before and after 1 to 2 weeks ' and 3
      months (chronic) of antihypertensive treatment with losartan-hydrochlorothiazide
      (Hyzaar). MSNA and hemodynamics were measured supine, during a Valsalva maneuver
      (VM), and at 70 degrees head-up tilt (HUT) for 10 minutes. Data were compared
      with those obtained in 7 age-matched healthy controls. We found that Hyzaar
      lowered mean BP acutely and chronically by 20+/-4 and 23+/-3 mm Hg (both P<0.01)
      but did not change HR. Supine MSNA increased by 43+/-11% and 34+/-11% after acute
      and chronic treatment (both P<0.01). However, MSNA responses to VM and HUT did
      not differ after treatment compared with before treatment, indicating unchanged
      reflex control. These data indicate that sympathetic neural activity was
      augmented substantially by antihypertensive treatment with Hyzaar, consistent
      with an ongoing baroreflex unloading, and did not return to baseline or "reset"
      after 3 months of therapy. We speculate that persistent and marked sympathetic
      activation by the baroreflex may be a potential mechanism for hypertension that
      is refractory to antihypertensive therapy and may provide a target mechanism for
      persistent morbidity despite adequate BP control.

PMID- 15738345
TI  - Beneficial effects of circulating progenitor endothelial cells activated by
      angiotensin receptor antagonists.

PMID- 15738346
TI  - PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish
      whites.
AB  - PGC-1alpha is a coactivator of numerous transcription factors and is expressed in
      tissues with high energy demands and abundant in mitochondria. It is induced in
      the myocardium on fasting and physical exercise, and cardiac-specific
      overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser
      polymorphism of PGC-1alpha has previously shown association with arterial
      hypertension among Austrian men. Thus, we aimed at investigating this
      relationship in the Danish white population. The Gly482Ser polymorphism was
      genotyped in a total of 2562 Danish white subjects using polymerase chain
      reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView
      locked nucleic acid assay (LNA), and the relationships of this variant with blood
      pressure levels and arterial hypertension were analyzed. Furthermore, we
      performed a combined analysis of the data from the present study in combination
      with previously published results. The Ser/Ser genotype was significantly
      associated with a reduced risk of hypertension and with lower systolic,
      diastolic, and mean arterial blood pressure levels, predominantly among women.
      Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser
      genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56
      to 0.86) for hypertension compared with Gly/X carriers (P=0.001). In conclusion,
      the Ser allele of PGC-1alpha Gly482Ser confers a significantly reduced risk of
      hypertension in whites. Further studies are needed to elucidate the differential
      role of this polymorphism in men and women.

PMID- 15738347
TI  - Components of the metabolic syndrome and carotid atherosclerosis: role of
      elevated blood pressure.
AB  - Elevated blood pressure is among the factors that contribute to the metabolic
      syndrome (MetS). It is not known whether subjects with MetS and elevated blood
      pressure are at the same cardiovascular risk as subjects with MetS but without
      elevated blood pressure. To clarify this point, we have evaluated the prevalence
      of carotid atherosclerosis in subjects with MetS with or without elevated blood
      pressure. A large population was examined (842 women and 1011 men). Blood
      pressure, lipids, glucose, and waist were measured by routine methods. Carotid
      atherosclerosis was evaluated by echo Doppler examination. The prevalence of MetS
      was 24.4% in women and 28.7% in men. The prevalence of carotid atherosclerosis
      was 35.1% in women and 37.3% in men (p=NS), and increased with increasing number
      of MetS components. Age, smoking, and systolic blood pressure (SBP) were
      associated with the presence of carotid atherosclerosis (logistic model), whereas
      age, high-density lipoprotein cholesterol, and SBP were associated with the
      extent of atherosclerosis (linear model). When comparing subjects with an equal
      number of MetS components, the prevalence of carotid atherosclerosis was
      significantly higher in subjects with elevated blood pressure than in those
      without. No difference in carotid atherosclerosis prevalence was found in
      subjects bearing or not bearing components of the syndrome other than elevated
      blood pressure. The present findings demonstrate that subjects with MetS and
      elevated blood pressure have increased carotid atherosclerosis compared with
      subjects with MetS but without elevated blood pressure. The diagnosis of MetS per
      se might not adequately identify subjects at elevated cardiovascular risk.

PMID- 15738348
TI  - Elevated pulse pressure is associated with low renal function in elderly patients
      with isolated systolic hypertension.
AB  - In the past decade, pulse pressure has emerged as a strong predictor of
      cardiovascular morbidity and mortality. During aging, elevation of pulse pressure
      is a consequence of stiffening of the arterial wall. The relationship between
      pulse pressure and the renal aging process was studied in a cohort of 212
      patients with never-treated isolated systolic hypertension. Glomerular filtration
      rate and effective renal plasma flow were measured using constant infusion of
      technetium 99m (99mTc)-DTPA and 131I-ortho-iodohippurate, respectively, and timed
      urine collections. The relationship between pulse pressure and renal function was
      studied using a linear regression model in the total population and in 40 to 49,
      50 to 59, and 60 years and older age categories. In the whole population, there
      was an inverse relationship between pulse pressure and glomerular filtration
      rate; however, this relation did not persist after adjustment for age. In fact,
      the inverse relationship between pulse pressure and glomerular filtration rate
      was only present in patients 60 years of age or older. This relationship in
      elderly patients remained after adjustment for age, gender, MAP, and
      cardiovascular risk factors (P=0.006). It is suggested that pulse pressure, a
      marker of arterial stiffening, may have a detrimental influence on the age
      related decline in glomerular filtration rate, after 60 years of age in patients
      with never-treated isolated systolic hypertension.

PMID- 15738349
TI  - Multiple quantitative trait loci for blood pressure interacting epistatically and
      additively on Dahl rat chromosome 2.
AB  - Our previous work demonstrated 2 quantitative trait loci (QTLs), C2QTL1 and
      C2QTL2, for blood pressure (BP) located on chromosome (Chr) 2 of Dahl salt
      sensitive (DSS) rats. However, for a lack of markers, the 2 congenic strains
      delineating C2QTL1 and C2QTL2 could not be separated. The position of the C2QTL1
      was only inferred by comparing 2 congenic strains, one having and another lacking
      a BP effect. Furthermore, it was not known how adjacent QTLs would interact with
      one another on Chr 2. In the current investigation, first, a critical chromosome
      marker was developed to separate 2 C2QTLs. Second, a congenic substrain was
      created to cover a chromosome fragment thought to harbor C2QTL1. Finally, a
      series of congenic strains was produced to systematically and comprehensively
      cover the entire Chr 2 segment containing C2QTL2 and other regions previously
      untested. Consequently, a total of 3 QTLs were discovered, with C2QTL3 located
      between C2QTL1 and C2QTL2. C2QTL1, C2QTL2, and C2QTL3 reside in chromosome
      segments of 5.7 centiMorgan (cM), 3.5 cM, and 1.5 cM, respectively. C2QTL1
      interacted epistatically with either C2QTL2 or C2QTL3, whereas C2QTL2 and C2QTL3
      showed additive effects to each other. These results suggest that BP QTLs closely
      linked in a segment interact epistatically and additively to one another on Chr
      2.

PMID- 15738350
TI  - Augmented endothelin vasoconstriction in intermittent hypoxia-induced
      hypertension.
AB  - We reported previously that simulating sleep apnea in rats by exposing them 7
      hours per day to intermittent hypoxia/hypercapnia (IH) elevates plasma endothelin
      1 and causes hypertension, which is reversed by an endothelin-1 antagonist. We
      hypothesized that in this model of sleep apnea-induced hypertension, vascular
      sensitivity to endothelin-1 is increased in combination with the elevated plasma
      endothelin-1 to cause the endothelin-1-dependent hypertension. In small
      mesenteric arteries with endothelial function disabled by passing air through the
      lumen, diameter and vessel wall [Ca2+] were recorded simultaneously. IH arteries
      demonstrated increased constrictor sensitivity to endothelin-1 (percentage max
      constriction 100+/-0% IH versus 80+/-10% Sham; P<0.05). This was accompanied by
      increased calcium sensitivity of IH arteries. In contrast, constrictor
      sensitivity and increases in vessel wall [Ca2+] to KCl and phenylephrine were not
      different between IH and Sham arteries. We have shown previously that endothelin
      1 constriction in mesenteric arteries is mediated by endothelin A receptors. In
      the current study, the selective increase in endothelin-1 constriction in IH
      resistance arteries was accompanied by increased expression of endothelin A
      receptor expression (densitometry units 271+/-23 IH versus 158+/-25 Sham;
      P<0.05). Thus, IH hypertension appears to cause alterations in signaling
      components unique to endothelin-1 at the receptor level and in postreceptor
      signaling that increases calcium sensitivity during endothelin A activation.
      Future studies will determine the specific changes in vascular smooth muscle
      signaling in IH hypertension causing this augmented contractile phenotype.

PMID- 15738351
TI  - Assessment of left ventricular torsional deformation by Doppler tissue imaging:
      validation study with tagged magnetic resonance imaging.
AB  - BACKGROUND: Left ventricular (LV) torsional deformation is a sensitive index for
      LV performance but difficult to measure. The present study tested the accuracy of
      a novel method that uses Doppler tissue imaging (DTI) for quantifying LV torsion
      in humans with tagged magnetic resonance imaging (MRI) as a reference. METHODS
      AND RESULTS: Twenty patients underwent DTI and tagged MRI studies. Images of the
      LV were acquired at apical and basal short-axis levels to assess LV torsion. We
      calculated LV rotation by integrating the rotational velocity, determined from
      DTI velocities of the septal and lateral regions, and correcting for the LV
      radius over time. LV torsion was defined as the difference in LV rotation between
      the 2 levels. DTI rotational and torsional profiles throughout systole and
      diastole were compared with those by tagged MRI at isochronal points. Rotation
      and torsion by DTI were closely correlated with tagged MRI results during systole
      and early diastole (apical and basal rotation, r=0.87 and 0.90, respectively; for
      torsion, 0.84; P<0.0001, by repeated-measures regression models). Maximal torsion
      showed even better correlation (r=0.95, P<0.0001). CONCLUSIONS: The present study
      has shown that DTI can quantify LV torsional deformation over time. This novel
      method may facilitate noninvasive quantification of LV torsion in clinical and
      research settings.

PMID- 15738352
TI  - Clopidogrel loading with eptifibatide to arrest the reactivity of platelets:
      results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of
      Platelets (CLEAR PLATELETS) study.
AB  - BACKGROUND: Pretreatment is not the most common strategy practiced for
      clopidogrel administration in elective coronary stenting. Moreover, limited
      information is available on the antiplatelet pharmacodynamics of a 300-mg versus
      a 600-mg clopidogrel loading dose, and the comparative effect of eptifibatide
      with these regimens is unknown. METHODS AND RESULTS: Patients undergoing elective
      stenting (n=120) were enrolled in a 2x2 factorial study (300 mg clopidogrel with
      or without eptifibatide; 600 mg clopidogrel with or without eptifibatide)
      (Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets
      [CLEAR PLATELETS] Study). Clopidogrel was administered immediately after
      stenting. Aggregometry and flow cytometry were used to assess platelet
      reactivity. Eptifibatide added a > or =2-fold increase in platelet inhibition to
      600 mg clopidogrel alone at 3, 8, and 18 to 24 hours after stenting as measured
      by 5 micromol/L ADP-induced aggregation (P<0.001). Without eptifibatide, 600 mg
      clopidogrel produced better inhibition than 300 mg clopidogrel at all time points
      (P<0.001). Glycoprotein IIb/IIIa (GPIIb/IIIa) blockade was associated with lower
      cardiac marker release. Active GPIIb/IIIa expression was inhibited most in the
      groups treated with eptifibatide (P<0.05). CONCLUSIONS: In elective stenting
      without clopidogrel pretreatment, use of a GPIIb/IIIa inhibitor produces superior
      platelet inhibition and lower myocardial necrosis compared with high-dose (600
      mg) or standard-dose (300 mg) clopidogrel loading alone. In the absence of a
      GPIIb/IIIa inhibitor, 600 mg clopidogrel provides better platelet inhibition than
      the standard 300-mg dose. These results require confirmation in a large-scale
      clinical trial.

PMID- 15738353
TI  - Low-grade albuminuria and the risks of hypertension and blood pressure
      progression.
AB  - BACKGROUND: It has been postulated that glomerular hyperfiltration and
      endothelial dysfunction are early features of essential hypertension that may
      antedate blood pressure elevation. Microalbuminuria, a marker of glomerular
      hyperfiltration and endothelial dysfunction, has been described in individuals
      with established hypertension, but its role as a biomarker of preclinical stages
      of this disease has not been investigated prospectively. METHODS AND RESULTS: We
      examined the association between urinary albumin excretion and the risks of
      hypertension and blood pressure progression in 1499 nonhypertensive individuals
      (58% women) without diabetes. During a mean follow-up of 2.9 years, 230
      participants (15%) developed hypertension and 499 (33%) progressed to a higher
      blood pressure category (defined by the sixth report of the Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
      Pressure). In multivariable logistic regressions that adjusted for known risk
      factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of
      incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment
      in log UACR). Compared with those in the lowest UACR quartile, participants in
      the highest quartile (men: >6.66 mg/g; women: >15.24 mg/g) had an approximately 2
      fold risk of developing hypertension (adjusted OR 1.93, P=0.006) and 1.5-fold
      risk of blood pressure progression (adjusted OR 1.45, P=0.03). CONCLUSIONS:
      Urinary albumin excretion predicts blood pressure progression in nondiabetic,
      nonhypertensive individuals incrementally over established risk factors and at
      levels well below the conventional threshold for microalbuminuria. UACR may be a
      useful biomarker for identifying individuals most likely to develop hypertension.

PMID- 15738355
TI  - Surgical treatment of atrial fibrillation via energy ablation.

PMID- 15738354
TI  - Molecular magnetic resonance imaging of coronary thrombosis and pulmonary emboli
      with a novel fibrin-targeted contrast agent.
AB  - BACKGROUND: The differential diagnosis of acute chest pain is challenging,
      especially in patients with normal ECG findings, and may include coronary
      thrombosis or pulmonary emboli. The aim of this study was to investigate the
      novel fibrin-specific contrast agent EP-2104R for molecular targeted MR imaging
      of coronary thrombosis and pulmonary emboli. METHODS AND RESULTS: Fresh clots
      were engineered ex vivo from human blood and delivered in the lungs and coronary
      arteries of 7 swine. Subsequent molecular MR imaging was performed with a
      navigator-gated free-breathing and cardiac-triggered 3D inversion-recovery black
      blood gradient-echo sequence before and after systemic administration of 7.5
      micromol/kg EP-2104R. Two swine served as the control group. MR images were
      analyzed by 2 investigators, and contrast-to-noise ratio and gadolinium
      concentration in the clots were assessed. Before contrast media application, no
      thrombi were visible. After contrast administration, all 32 pulmonary emboli, 3
      emboli in the right heart, and 5 coronary thrombi were selectively visualized as
      white spots with a mean contrast-to-noise ratio of 32+/-19. The average
      gadolinium concentration from all 3 types of thrombi was 144+/-79 micromol/L.
      CONCLUSIONS: Molecular MR imaging with the fibrin-targeted contrast-agent EP
      2104R allows selective visualization of acute coronary, cardiac, and pulmonary
      thrombi.

PMID- 15738356
TI  - Images in cardiovascular medicine. Mitral valve prolapse associated with
      accessory mitral valve.

PMID- 15738357
TI  - Images in cardiovascular medicine. Provocable pressure gradient across an
      anomalous left main coronary artery: a unique diagnostic tool.

PMID- 15738358
TI  - Letter regarding article by Klausen et al, "very low levels of microalbuminuria
      are associated with increased risk of coronary heart disease and death
      independently of renal function, hypertension, and diabetes".

PMID- 15738359
TI  - Letter regarding article by Frigiola et al, "pulmonary regurgitation is an
      important determinant of right ventricular contractile dysfunction in patients
      with surgically repaired tetralogy of Fallot".

PMID- 15738360
TI  - Influence of changes of blood pressure on vascular angiotensin II receptor
      subtype expression.

PMID- 15738361
TI  - Late follow-up from RAVEL: transition from intention to observation.

PMID- 15738362
TI  - Recommendations for the establishment of stroke systems of care: recommendations
      from the American Stroke Association's Task Force on the Development of Stroke
      Systems.

PMID- 15738363
TI  - Notice of retraction.

PMID- 15738364
TI  - Population-based screening for celiac disease: improvement in morbidity and
      mortality from osteoporosis?

PMID- 15738365
TI  - Integrating palliative care into heart failure care.
AB  - Heart failure is a condition for which both palliative care and hospice care can
      be appropriate. The disease's increasing prevalence and predilection for elderly
      patients with significant comorbidity underscore the need to integrate these
      modes of care with the acute care approach that has dominated heart failure
      treatment. We propose integration of a palliative care approach early in the
      course of heart failure treatment and a tiered process for selecting patients for
      hospice care. A transition of the focus to palliative care rather than mortality
      reduction should occur over time, when clinical status deteriorates and advanced
      therapeutic options become inappropriate or ineffective. Failure to respond to
      the need for palliative care puts at risk the mandate to treat the patient with
      heart failure during the entire course of illness.

PMID- 15738366
TI  - Risk of proximal colon neoplasia with distal hyperplastic polyps: a meta
      analysis.
AB  - BACKGROUND: Most guidelines for colorectal cancer screening do not consider
      distal hyperplastic polyps (HPs) to be markers for proximal colon neoplasia.
      However, many studies have shown an increased risk of proximal neoplasia (PN) in
      patients with distal HPs. We performed a systematic review to assess the
      association between distal HPs and PN. METHODS: We identified studies that
      compared the prevalence of PN and proximal advanced neoplasia in patients with
      distal HPs vs controls. Two masked investigators extracted data on individuals
      with distal HPs, distal adenomas, or no distal polyps. Using the DerSimonian and
      Laird method, we calculated summary risk ratios. Extensive subgroup analysis was
      performed. RESULTS: The prevalence of PN and proximal advanced neoplasia in
      persons with distal HPs was 26.0% and 4.4%, respectively. In studies comparing
      the risk of PN in patients with distal HPs vs those with no distal polyps, the
      summary risk ratio was 1.81 (95% confidence interval, 1.20-2.73). However, this
      increased risk disappeared if only high-quality studies on screening patients
      were considered. The risk ratio was 0.69 (95% confidence interval, 0.60-0.80)
      when comparing the risk of PN in those with distal HPs vs those with distal
      adenomas. CONCLUSIONS: Overall, patients with distal HPs have an intermediate
      risk of PN compared with those with distal adenomas or no distal polyps; however,
      in asymptomatic screening individuals, there is no increased risk of PN or
      proximal advanced neoplasia. The discovery of HPs on screening flexible
      sigmoidoscopy should not automatically prompt follow-up colonoscopy.

PMID- 15738367
TI  - Increased prevalence of celiac disease and need for routine screening among
      patients with osteoporosis.
AB  - BACKGROUND: There is an increased prevalence of osteoporosis among patients with
      celiac disease. However, the relative prevalence of celiac disease among
      osteoporotic and nonosteoporotic populations is not known, and the benefit of
      screening the osteoporotic population for celiac disease remains controversial.
      METHODS: We evaluated 840 individuals, 266 with and 574 without osteoporosis,
      from the Washington University Bone Clinic by serologic screening for celiac
      disease. Individuals with positive serologic test results for antitissue
      transglutaminase or antiendomysial antibody were offered endoscopic intestinal
      biopsy to confirm the diagnosis of celiac disease. Individuals with biopsy-proven
      celiac disease were treated with a gluten-free diet and followed up for
      improvement in bone mineral density. RESULTS: Twelve (4.5%) of 266 patients with
      osteoporosis and 6 (1.0%) of 574 patients without osteoporosis tested positive by
      serologic screening for celiac disease. All but 2 serologically positive
      individuals underwent in-testinalbiopsy. Nine osteoporotic patients and 1
      nonosteoporotic patient had positive biopsy results. The prevalence of biopsy
      proven celiac disease was 3.4% among the osteoporotic population and 0.2% among
      the nonosteoporotic population. All biopsy-positive individuals tested positive
      by antitissue transglutaminase and antiendomysial antibody. The antitissue
      transglutaminase levels correlated with the severity of osteoporosis as measured
      by T score, demonstrating that the more severe the celiac disease the more severe
      the resulting osteoporosis. Treatment of the patients with celiac disease with a
      gluten-free diet resulted in marked improvement in T scores. CONCLUSIONS: The
      prevalence of celiac disease among osteoporotic individuals (3.4%) is much higher
      than that among nonosteoporotic individuals (0.2%). The prevalence of celiac
      disease in osteoporosis is high enough to justify a recommendation for serologic
      screening of all patients with osteoporosis for celiac disease.

PMID- 15738368
TI  - Forgoing treatment at the end of life in 6 European countries.
AB  - BACKGROUND: Modern medicine provides unprecedented opportunities in diagnostics
      and treatment. However, in some situations at the end of a patient's life, many
      physicians refrain from using all possible measures to prolong life. We studied
      the incidence of different types of treatment withheld or withdrawn in 6 European
      countries and analyzed the main background characteristics. METHODS: Between June
      2001 and February 2002, samples were obtained from deaths reported to registries
      in Belgium, Denmark, Italy, the Netherlands, Sweden, and Switzerland. The
      reporting physician was then sent a questionnaire about the medical decision
      making process that preceded the patient's death. RESULTS: The incidence of
      nontreatment decisions, whether or not combined with other end-of-life decisions,
      varied widely from 6% of all deaths studied in Italy to 41% in Switzerland. Most
      frequently forgone in every country were hydration or nutrition and medication,
      together representing between 62% (Belgium) and 71% (Italy) of all treatments
      withheld or withdrawn. Forgoing treatment estimated to prolong life for more than
      1 month was more common in the Netherlands (10%), Belgium (9%), and Switzerland
      (8%) than in Denmark (5%), Italy (3%), and Sweden (2%). Relevant determinants of
      treatment being withheld rather than withdrawn were older age (odds ratio [OR],
      1.53; 95% confidence interval [CI], 1.31-1.79), death outside the hospital (death
      in hospital: OR, 0.80; 95% CI, 0.68-0.93), and greater life-shortening effect
      (OR, 1.75; 95% CI, 1.27-2.39). CONCLUSIONS: In all of the participating
      countries, life-prolonging treatment is withheld or withdrawn at the end of life.
      Frequencies vary greatly among countries. Low-technology interventions, such as
      medication or hydration or nutrition, are most frequently forgone. In older
      patients and outside the hospital, physicians prefer not to initiate life
      prolonging treatment at all rather than stop it later.

PMID- 15738369
TI  - Invasive amebiasis as an emerging parasitic disease in patients with human
      immunodeficiency virus type 1 infection in Taiwan.
AB  - BACKGROUND: Whether risk of invasive amebiasis due to Entamoeba histolytica is
      higher among human immunodeficiency virus (HIV)-infected persons than uninfected
      persons remains unclear, although intestinal colonization by Entamoeba dispar is
      common among men who have sex with men. Our objective was to determine the
      prevalence of invasive amebiasis and intestinal colonization by E histolytica and
      E dispar in HIV-infected persons and uninfected controls. METHODS: We assessed
      the prevalence of invasive amebiasis by case review of 951 HIV-infected persons
      and by serologic studies of 634 of the 951 HIV-infected persons, 429 uninfected
      controls with gastrointestinal symptoms, and 178 uninfected healthy controls
      using indirect hemagglutination antibody assay. We assessed the rate of
      intestinal colonization by E histolytica and E dispar by fecal antigen and
      polymerase chain reaction tests in 332 asymptomatic HIV-infected persons and 144
      of the 178 uninfected healthy controls. RESULTS: Forty-nine (5.2%) of 951 HIV
      infected persons had 51 episodes of invasive amebiasis. A high indirect
      hemagglutination antibody titer was detected in 39 (6.2%) of 634 HIV-infected
      persons compared with 10 (2.3%) of 429 uninfected controls with gastrointestinal
      symptoms and 0 of 178 uninfected healthy controls (P<.001). Stool specimens from
      40 (12.1%) of 332 HIV-infected persons and 2 (1.4%) of 144 uninfected healthy
      controls were positive for E histolytica or E dispar antigen (P<.001). Ten
      (25.0%) of the 40 antigen-positive stool specimens from HIV-infected persons
      contained E histolytica. CONCLUSION: Persons infected with HIV in Taiwan are at
      increased risk for invasive amebiasis and exhibit a relatively high frequency of
      elevated antibody titers and intestinal colonization with E histolytica.

PMID- 15738371
TI  - The changing incidence of AIDS events in patients receiving highly active
      antiretroviral therapy.
AB  - BACKGROUND: Although the incidence of most AIDS events declines after initiation
      of highly active antiretroviral therapy (HAART), this decline is more rapid for
      some conditions than others. We herein describe the decline in incidence of AIDS
      defining events among 12,574 antiretroviral-naive individuals who started HAART
      in the Antiretorviral Therapy Cohort Collaboration and determined whether the
      rate of decline is similar for events with different etiologies. METHODS: Rates
      of AIDS were calculated for the periods 0 to 3, 4 to 6, 7 to 12, 13 to 24, and 25
      to 36 months after starting HAART. Changes in incidence over time were
      investigated using Poisson regression. RESULTS: During 22 958 person-years of
      follow-up, 928 AIDS events developed (25.3% viral, 24.6% bacterial, 20.7% fungal,
      8.1% protozoal, and 21.2% other). The incidence of any AIDS event declined from
      129.3 (95% confidence interval [CI], 116.7-141.8) per 1000 person-years in the
      first 3 months to 13.2 (95% CI, 9.4-17.0) in the third year after starting HAART
      (P<.001). The rate of decline in incidence was greatest for events with a viral
      etiology (87.0% per year) and lowest for those with a fungal etiology (54.0% per
      year). In the third year, fungal events represented 37.0% of AIDS events that
      occurred. After adjustment for the CD4 count and human immunodeficiency virus 1
      RNA level, changes in the incidence of bacterial and viral events from months 0
      to 6 and 7 to 12 remained significant, suggesting that changes in these markers
      did not fully explain the changes in incidence seen. CONCLUSION: Although the
      incidence of all AIDS-defining events decreased substantially after starting
      HAART, the pattern of decline was most pronounced for events with a viral
      etiology.

PMID- 15738372
TI  - Unintended medication discrepancies at the time of hospital admission.
AB  - BACKGROUND: Prior studies suggest that unintended medication discrepancies that
      represent errors are common at the time of hospital admission. These errors are
      particularly worthy of attention because they are not likely to be detected by
      computerized physician order entry systems. METHODS: We prospectively studied
      patients reporting the use of at least 4 regular prescription medications who
      were admitted to general internal medicine clinical teaching units. The primary
      outcome was unintended discrepancies (errors) between the physicians' admission
      medication orders and a comprehensive medication history obtained through
      interview. We also evaluated the potential seriousness of these discrepancies.
      All discrepancies were reviewed with the medical team to determine if they were
      intentional or unintentional. All unintended discrepancies were rated for their
      potential to cause patient harm. RESULTS: After screening 523 admissions, 151
      patients were enrolled based on the inclusion criteria. Eighty-one patients
      (53.6%; 95% confidence interval, 45.7%-61.6%) had at least 1 unintended
      discrepancy. The most common error (46.4%) was omission of a regularly used
      medication. Most (61.4%) of the discrepancies were judged to have no potential to
      cause serious harm. However, 38.6% of the discrepancies had the potential to
      cause moderate to severe discomfort or clinical deterioration. CONCLUSIONS:
      Medication errors at the time of hospital admission are common, and some have the
      potential to cause harm. Better methods of ensuring an accurate medication
      history at the time of hospital admission are needed.

PMID- 15738373
TI  - Sex differences in the effect of diabetes duration on coronary heart disease
      mortality.
AB  - BACKGROUND: It is not known whether the coronary heart disease (CHD) mortality
      risk associated with recent (RDM; <10 years) or long-standing diabetes mellitus
      (LDM; > or =10 years) varies by sex. METHODS: The relationship between diabetes
      duration and CHD mortality was evaluated among 10 871 adults (aged 35-74 years at
      baseline) using the 1971-1992 National Health and Nutrition Examination Survey
      Epidemiologic Follow-up Study. RESULTS: The CHD mortality rates per 1000 person
      years in men with no myocardial infarction (MI) or diabetes, MI only, RDM only,
      LDM only, MI and RDM, and MI and LDM were 5.5 (95% confidence interval, 4.8-6.2),
      15.2 (11.6-20.0), 13.2 (7.9-22.1), 11.4 (6.4-20.3), 36.0 (16.7-77.7), and 35.4
      (14.0-89.7), respectively. The corresponding rates in women were 2.9 (2.5-3.3),
      7.3 (5.0-10.8), 5.2 (3.5-7.7), 10.7 (7.5-15.5), 9.3 (4.3-19.9), and 21.6 (6.1
      76.0), respectively. Compared with MI, the multivariate hazard ratios and their
      95% confidence intervals (adjusted for age, race, smoking, hypertension, total
      cholesterol level, and body mass index) for fatal CHD in men with RDM, LDM, MI
      and RDM, and MI and LDM were 0.7 (0.3-1.3), 0.8 (0.4-1.4), 3.2 (1.4-7.4), and 2.4
      (0.8-6.7), respectively. The corresponding ratios in women were 0.9 (0.6-1.3),
      1.8 (1.1-3.2), 1.3 (0.5-3.5), and 1.6 (0.2-10.9), respectively. CONCLUSIONS: In
      men, RDM and LDM were associated with as high a risk for CHD death as MI. In
      women, although RDM had a CHD mortality risk similar to MI, LDM had an even
      greater risk. Because women with LDM are at very high risk for CHD mortality,
      current guidelines may need to be further refined to match intensity of treatment
      to risk in these women.

PMID- 15738374
TI  - Performance of screening questionnaires and risk scores for undiagnosed diabetes:
      the KORA Survey 2000.
AB  - BACKGROUND: Validation of published screening questionnaires and risk scores for
      undiagnosed diabetes has typically not been performed in independent population
      samples. METHODS: Oral glucose tolerance tests were performed in 1353
      participants (aged 55-74 years) without known diabetes in the Cooperative Health
      Research in the Region of Augsburg (KORA) Survey 2000, Augsburg, Germany.
      Sensitivity, specificity, and the area under the receiver operating
      characteristic curve (AUC) for undiagnosed diabetes were calculated for various
      screening questionnaires. RESULTS: Four screening tests (Rotterdam Diabetes
      Study, Cambridge Risk Score, San Antonio Heart Study, and Finnish Diabetes Risk
      Score) were applied to the KORA data. The AUCs were 61% (95% confidence interval
      [CI], 56%-66%) for the Rotterdam Diabetes Study, 65% (95% CI, 60%-69%) for the
      Finnish Diabetes Risk Score (P=.10 vs Rotterdam), and 67% (95% CI, 62%-72%) for
      the Cambridge Risk Score (P<.001 vs Rotterdam). A predictive model including
      fasting glucose level (San Antonio Heart Study) yielded an AUC of 90% (P<.01 vs
      all 3 questionnaires); however, this was not significantly different from fasting
      glucose level alone (AUC, 89%; P=.46). The sensitivities, specificities, and
      predictive values of questionnaires were substantially lower than originally
      described, which was mainly due to population variation of risk factors compared
      with the KORA sample (age, body mass index, antihypertensive medication, and
      smoking). CONCLUSIONS: Currently proposed questionnaires yielded low validity
      when applied to a new population, most likely due to differences in population
      characteristics. Performance of diabetes risk questionnaires or scores must be
      assessed in the target population where they will be applied.

PMID- 15738375
TI  - Pulse oximetry as a potential screening tool for lower extremity arterial disease
      in asymptomatic patients with diabetes mellitus.
AB  - BACKGROUND: Lower extremity arterial disease (LEAD) is common and underdiagnosed
      in patients with diabetes mellitus and is associated with higher total mortality.
      METHODS: We compared the accuracy of pulse oximetry, the ankle-brachial index
      (ABI), and the combination of the two to diagnose LEAD in consecutive outpatients
      with type 2 diabetes who had no symptoms of LEAD, in a primary care setting.
      Exclusions were age younger than 40 years, known LEAD, or typical symptoms of
      LEAD. Fifty-seven patients were enrolled. All patients had (1) ABI measurement;
      (2) pulse oximetry to measure Sao2 of their index fingers and big toes in the
      supine position and at 12-in elevation; and (3) Doppler waveform analysis of the
      lower extremity arteries. The ABI was considered abnormal if it was less than
      0.9. Pulse oximetry of the toes was considered abnormal if the Sao2 was more than
      2% lower from the finger or on 12-in elevation of the foot. The combination was
      considered positive if either the ABI or pulse oximetry was positive for LEAD and
      negative if both were negative. We defined LEAD as monophasic waveforms on
      waveform analysis. RESULTS: Of our patients, 31% had LEAD. Pulse oximetry had a
      sensitivity of 77% (95% confidence interval [CI], 61%-88%) and a specificity of
      97% (95% CI, 91%-99%); ABI had a sensitivity of 63% (95% CI, 46%-77%) and a
      specificity of 97% (95% CI, 91%-99%). Positive likelihood ratios were 30 (95% CI,
      7.6-121) for pulse oximetry and 24.8 (95% CI, 6.2-99.8) for ABI; negative
      likelihood ratios were 0.23 (95% CI, 0.12-0.43) for pulse oximetry and 0.38 (95%
      CI, 0.25-0.59) for ABI. For the combination, sensitivity was 86% (95% CI, 71%
      94%) and specificity was 92% (95% CI, 84%-96%). CONCLUSIONS: Pulse oximetry of
      the toes seems as accurate as ABI to screen for LEAD in patients with type 2
      diabetes. Combination of the two tests increases sensitivity.

PMID- 15738376
TI  - Type 2 diabetes, glycemic control, and continuous positive airway pressure in
      obstructive sleep apnea.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is a prevalent condition associated
      with significant comorbidities, including hypertension, obesity, cardiovascular
      disease, and insulin resistance. It has been previously shown that the severity
      of insulin resistance is related to the severity of SDB. METHODS: Using a 72-hour
      continuous glucose monitoring system, we studied changes in interstitial glucose
      levels and measured hemoglobin A1c levels in 25 patients with type 2 diabetes
      mellitus before and after continuous positive airway pressure (CPAP) treatment
      for SDB. RESULTS: With a mean +/- SD CPAP treatment period of 83 +/- 50 days, the
      mean +/- SD 1-hour postprandial glucose values were significantly reduced for
      breakfast (191 +/- 68 mg/dL to 130 +/- 41 mg/dL [10.6 +/- 3.8 mmol/L to 7.2 +/-
      2.3 mmol/L]), lunch (196 +/- 70 mg/dL to 138 +/- 49 mg/dL [10.9 +/- 3.9 mmol/L to
      7.7 +/- 2.7 mmol/L]), and dinner (199 +/- 66 mg/dL to 137 +/- 48 mg/dL [11.0 +/-
      3.7 mmol/L to 7.6 +/- 2.7 mmol/L]). In the 17 patients with a baseline hemoglobin
      A1c level greater than 7%, there was a significant reduction in hemoglobin A1c
      level (9.2% +/- 2.0% to 8.6% +/- 1.8%). Furthermore, in subjects who used CPAP
      for more than 4 h/d, the reduction in hemoglobin A1c level was significantly
      correlated with days of CPAP use. There was no such correlation in subjects who
      used CPAP for 4 h/d or less. CONCLUSIONS: These findings suggest that SDB is
      pathophysiologically related to impaired glucose homeostasis, and that CPAP can
      be an important therapeutic approach for diabetic patients with SDB.

PMID- 15738377
TI  - Prospective validation of a prediction model for isolating inpatients with
      suspected pulmonary tuberculosis.
AB  - BACKGROUND: Current guidelines for the control of nosocomial transmission of
      tuberculosis (TB) recommend respiratory isolation for all patients with suspected
      TB. Application of these guidelines has resulted in many patients without TB
      being isolated on admission to the hospital, significantly increasing hospital
      costs. This study was conducted to prospectively validate a clinical decision
      rule to predict the need for respiratory isolation in inpatients with suspected
      TB. METHODS: A cohort of 516 individuals, who presented to 2 New York City
      hospitals between January 16, 2001, and September 29, 2002, and who were isolated
      on admission for clinically suspected TB, were enrolled in the study. Face-to
      face interviews were conducted to determine the presence of clinical variables
      associated with TB in the prediction model, including TB risk factors, clinical
      symptoms, and findings from physical examination and chest radiography. RESULTS:
      Of the 516 patients, 19 were found to have TB (prevalence, 3.7%; 95% confidence
      interval [CI], 2.2%-5.7%). The prediction rule had a sensitivity of 95% (95% CI,
      74%-100%) and a specificity of 35% (95% CI, 31%-40%). Using a prevalence of TB of
      3.7%, the positive predictive value was 9.6% and the negative predictive value
      was 99.7%. CONCLUSIONS: Among inpatients with suspected active pulmonary TB who
      are isolated on admission to the hospital, a prediction rule based on clinical
      and chest radiographic findings accurately identified patients at low risk for
      TB. Approximately one third of the unnecessary episodes of respiratory isolation
      could have been avoided had the prediction rule been applied. Future studies
      should assess the feasibility of implementing the rule in clinical practice.

PMID- 15738378
TI  - Quality of care of international and Canadian medical graduates in acute
      myocardial infarction.
AB  - BACKGROUND: International medical graduates (IMGs) make up a substantial
      proportion of the physician workforce and play an important role in the care of
      patients with acute myocardial infarction (AMI). There are concerns that IMGs may
      provide inferior medical care compared with locally trained medical graduates,
      but that has not been established. METHODS: We performed a retrospective cohort
      study of linked administrative databases containing health care claims of
      physicians' service payments, hospital discharge abstracts, and patients' vital
      status. We included 127,275 AMI patients admitted between April 1, 1992, and
      March 31, 2000, to acute care hospitals in Ontario. We then compared the risk
      adjusted mortality rates and adjusted use of secondary prevention medications and
      cardiac invasive procedures in patients treated by IMGs vs Canadian medical
      graduates. RESULTS: Of the 127,275 admitted AMI patients, 28,061 (22.0%) were
      treated by IMGs and 99,214 (78.0%) by Canadian medical graduates. The risk
      adjusted mortality rates of IMG- and Canadian medical graduate-treated patients
      were not significantly different at 30 days (13.3% vs 13.4%, P = .57) and at 1
      year (21.8% vs 21.9%, P = .63). Furthermore, AMI patients treated by both groups
      had similar adjusted likelihood of receiving secondary prevention medications at
      90 days and cardiac invasive procedures at 1 year. CONCLUSIONS: The use of
      secondary prevention medications and cardiac procedures and the mortality of AMI
      patients were similar, regardless of the origin of medical education of the
      admitting physician. This information places the care provided by IMGs into
      perspective and supports the ability of well-selected IMGs in caring for AMI
      patients.

PMID- 15738379
TI  - Bortezomib-induced severe hepatitis in multiple myeloma: a case report.
AB  - Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity.
      Its toxicity is manageable, and the most frequent adverse effects mainly consist
      of gastrointestinal symptoms, peripheral neuropathy, neuropatic pain, and
      thrombocytopenia. Severe liver toxicity has not been previously recognized. A
      patient with relapsed multiple myeloma who developed bortezomib-induced severe
      recurrent hepatitis is described. The importance of recognizing this rare
      potential toxicity is highlighted in order to discontinue this agent if liver
      adverse reaction is suspected.

PMID- 15738380
TI  - Anemia with impaired erythropoietin response in diabetic patients.
AB  - BACKGROUND: Diabetes mellitus is associated with an increased prevalence of
      anemia, particularly in patients with nephropathy. We undertook this survey to
      determine the relationship between anemia and the renal production of
      erythropoietin in patients with diabetes mellitus. METHODS: The clinical data of
      722 patients were obtained, including markers of diabetic complications.
      Erythropoietin levels were measured in the same samples. Patients with a full
      blood cell count, iron indexes, and renal function within the normal range (n =
      151) were used to define the reference range for this population. Anemic patients
      who had erythropoietin levels within this range were defined as having an
      "inappropriate erythropoietin response to anemia." RESULTS: Of the 722 patients,
      168 (23.3%) had anemia, of whom 130 (77.4%) had erythropoietin levels
      inappropriately within the normal range. Although 55.4% of anemic patients had
      moderate renal impairment, erythropoietin levels were also inappropriately low in
      69.2% of anemic patients with normal renal function. However, most of these
      patients (17 of 26) had diabetic kidney disease, as denoted by albuminuria.
      CONCLUSIONS: The failure to produce erythropoietin in response to a declining
      hemoglobin level is a common contributor to anemia in patients with diabetes
      mellitus. This seems to be a manifestation of diabetic kidney disease, in the
      presence or absence of renal impairment.

PMID- 15738381
TI  - The usefulness of sputum gram stain and culture.

PMID- 15738382
TI  - The "bupropion for smoking cessation" trial from a family practice perspective.

PMID- 15738383
TI  - Distant charge transport.

PMID- 15738384
TI  - Independence of replisomes in Escherichia coli chromosomal replication.
AB  - In Escherichia coli DNA replication is carried out by the coordinated action of
      the proteins within a replisome. After replication initiation, the two
      bidirectionally oriented replisomes from a single origin are colocalized into
      higher-order structures termed replication factories. The factory model
      postulated that the two replisomes are also functionally coupled. We tested this
      hypothesis by using DNA combing and whole-genome microarrays. Nascent DNA
      surrounding oriC in single, combed chromosomes showed instead that one replisome,
      usually the leftward one, was significantly ahead of the other 70% of the time.
      We next used microarrays to follow replication throughout the genome by measuring
      DNA copy number. We found in multiple E. coli strains that the replisomes are
      independent, with the leftward replisome ahead of the rightward one. The size of
      the bias was strain-specific, varying from 50 to 130 kb in the array results.
      When we artificially blocked one replisome, the other continued unabated, again
      demonstrating independence. We suggest an improved version of the factory model
      that retains the advantages of threading DNA through colocalized replisomes at
      about equal rates, but allows the cell flexibility to overcome obstacles
      encountered during elongation.

PMID- 15738385
TI  - Incorporating structure to predict microRNA targets.
AB  - MicroRNAs (miRNAs) are a recently discovered set of regulatory genes that
      constitute up to an estimated 1% of the total number of genes in animal genomes,
      including Caenorhabditis elegans, Drosophila, mouse, and humans [Lagos-Quintana,
      M., Rauhut, R., Lendeckel, W. & Tuschl, T. (2001) Science 294, 853-858; Lai, E.
      C., Tomancak, P., Williams, R. W. & Rubin, G.M. (2003) Genome Biol. 4, R42; Lau,
      N. C., Lim, L. P., Weinstein, E. G. & Bartel, D. P. (2001) Science 294, 858-862;
      Lee, R. C. & Ambros, V. (2001) Science 294, 862-8644; and Lee, R. C., Feinbaum,
      R. L. & Ambros, V. (1993) Cell 115, 787-798]. In animals, miRNAs regulate genes
      by attenuating protein translation through imperfect base pair binding to 3' UTR
      sequences of target genes. A major challenge in understanding the regulatory role
      of miRNAs is to accurately predict regulated targets. We have developed an
      algorithm for predicting targets that does not rely on evolutionary conservation.
      As one of the features of this algorithm, we incorporate the folded structure of
      mRNA. By using Drosophila miRNAs as a test case, we have validated our
      predictions in 10 of 15 genes tested. One of these validated genes is mad as a
      target for bantam. Furthermore, our computational and experimental data suggest
      that miRNAs have fewer targets than previously reported.

PMID- 15738387
TI  - Powerful screens for bacterial virulence proteins.

PMID- 15738386
TI  - Function and regulation of Tumbleweed (RacGAP50C) in neuroblast proliferation and
      neuronal morphogenesis.
AB  - Drosophila RacGAP50C and its homologues act as part of a complex with a kinesin
      like protein (Pavarotti/Zen-4) that is essential for the formation of the central
      spindle and completion of cytokinesis [Mishima, M., Kaitna, S. & Glotzer, M.
      (2002) Dev. Cell 2, 41-54; Somers, W. G. & Saint, R. (2003) Dev. Cell 4, 29-39;
      Jantsch-Plunger et al. (2000) J. Cell Biol. 149, 1391-1404]. We report here that
      RacGAP50C corresponds to the tumbleweed (tum) gene previously identified based on
      its defects in dendrite development of sensory neurons [Gao, F. B., Brenman, J.
      E., Jan, L. Y. & Jan, Y. N. (1999) Genes Dev. 13, 2549-2561]. Using mushroom body
      neurogenesis and morphogenesis as a model, we show that Tumbleweed (Tum),
      Pavarotti, and their association are required for neuroblast proliferation. Tum
      with a mutation predicted to disrupt the GTPase-activating protein (GAP) activity
      still largely retains its activity in regulating cell division but is impaired in
      its activity to limit axon growth. We also provide evidence that Tum and
      Pavarotti regulate the subcellular localization of each other in postmitotic
      neurons and that cytoplasmic accumulation of both proteins disrupts axon
      development in a GAP-dependent manner. Taken together with previous studies of
      RacGAP50C in regulating cytokinesis, we propose that Tum serves as a scaffolding
      protein in regulating cell division but acts as a GAP to limit axon growth in
      postmitotic neurons.

PMID- 15738388
TI  - Structure of human carboxypeptidase A4 with its endogenous protein inhibitor,
      latexin.
AB  - The only endogenous protein inhibitor known for metallocarboxypeptidases (MCPs)
      is latexin, a 25-kDa protein discovered in the rat brain. Latexin, alias
      endogenous carboxypeptidase inhibitor, inhibits human CPA4 (hCPA4), whose
      expression is induced in prostate cancer cells after treatment with histone
      deacetylase inhibitors. hCPA4 is a member of the A/B subfamily of MCPs and
      displays the characteristic alpha/beta-hydrolase fold. Human latexin consists of
      two topologically equivalent subdomains, reminiscent of cystatins, consisting of
      an alpha-helix enveloped by a curved beta-sheet. These subdomains are packed
      against each other through the helices and linked by a connecting segment
      encompassing a third alpha-helix. The enzyme is bound at the interface of these
      subdomains. The complex occludes a large contact surface but makes rather few
      contacts, despite a nanomolar inhibition constant. This low specificity explains
      the flexibility of latexin in inhibiting all vertebrate A/B MCPs tested, even
      across species barriers. In contrast, modeling studies reveal why the N/E
      subfamily of MCPs and invertebrate A/B MCPs are not inhibited. Major differences
      in the loop segments shaping the border of the funnel-like access to the protease
      active site impede complex formation with latexin. Several sequences ascribable
      to diverse tissues and organs have been identified in vertebrate genomes as being
      highly similar to latexin. They are proposed to constitute the latexin family of
      potential inhibitors. Because they are ubiquitous, latexins could represent for
      vertebrate A/B MCPs the counterparts of tissue inhibitors of metalloproteases for
      matrix metalloproteinases.

PMID- 15738389
TI  - Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic
      steatohepatitis and hepatic neoplasia.
AB  - Knockout studies have shown that the transcription factor Nrf1 is essential for
      embryonic development. Nrf1 has been implicated to play a role in mediating
      activation of oxidative stress response genes through the antioxidant response
      element (ARE). Because of embryonic lethality in knockout mice, analysis of this
      function in the adult knockout mouse was not possible. We report here that mice
      with somatic inactivation of nrf1 in the liver developed hepatic cancer. Before
      cancer development, mutant livers exhibited steatosis, apoptosis, necrosis,
      inflammation, and fibrosis. In addition, hepatocytes lacking Nrf1 showed
      oxidative stress, and gene expression analysis showed decreased expression of
      various ARE-containing genes, and up-regulation of CYP4A genes. These results
      suggest that reactive oxygen species generated from CYP4A-mediated fatty acid
      oxidation work synergistically with diminished expression of ARE-responsive genes
      to cause oxidative stress in mutant hepatocytes. Thus, Nrf1 has a protective
      function against oxidative stress and, potentially, a function in lipid
      homeostasis in the liver. Because the phenotype is similar to nonalcoholic
      steatohepatitis, these animals may prove useful as a model for investigating
      molecular mechanisms of nonalcoholic steatohepatitis and liver cancer.

PMID- 15738390
TI  - Time for chronotherapy? Clock genes dictate sensitivity to cyclophosphamide.

PMID- 15738391
TI  - A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair
      and chromosomal organization.
AB  - Through a genetic screen using myosin-like protein strains mlp1Delta mlp2Delta
      and biochemical purification, we identified a complex of eight proteins, each
      required for growth and DNA repair in Saccharomyces cerevisiae. Among the
      subunits are Mms21 that contains a putative Siz/PIAS (protein inhibitor of
      activated signal transducer and activator of transcription) RING domain
      characteristic of small ubiquitin-like modifier (SUMO) ligases, two structural
      maintenance-of-chromosome (Smc) proteins, Smc5 and Smc6, and a protein that
      contains an ubiquitin ligase signature domain. We show that these proteins
      colocalized to several distinct nuclear foci. Biochemical and genetic data
      demonstrated that Mms21 indeed functions as a SUMO ligase and that this activity
      requires the Siz/PIAS (protein inhibitor of activated signal transducer and
      activator of transcription) RING domain. The substrates for this SUMO ligase
      include a subunit of the octameric complex, Smc5, and the DNA repair protein
      Yku70. We further show that the abolition of the SUMO E3 activity of Mms21 leads
      to such disparate phenotypes as DNA damage sensitivity, defects in nucleolar
      integrity and telomere clustering, silencing, and length regulation. We propose
      that Mms21 sumoylates proteins involved in these diverse processes and that the
      other members of the complex, particularly Smc5/6, facilitate proper substrate
      sumoylation by localizing Mms21 to specific chromosomal regions.

PMID- 15738392
TI  - Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic
      factor gene.
AB  - Hereditary juvenile megaloblastic anemia due to vitamin B12 (cobalamin)
      deficiency is caused by intestinal malabsorption of cobalamin. In Imerslund
      Grasbeck syndrome (IGS), cobalamin absorption is completely abolished and not
      corrected by the administration of intrinsic factor (IF); if untreated, the
      disease is fatal. Biallelic mutations either in the cubilin (CUBN) or amnionless
      (AMN) gene cause IGS. In a series of families clinically diagnosed with likely
      IGS, at least six displayed no evidence of mutations in CUBN or AMN. A genome
      wide search for linkage followed by mutational analysis of candidate genes was
      performed in five of these families. A region in chromosome 11 showed evidence of
      linkage in four families. The gastric IF (GIF) gene located in this region
      harbored homozygous nonsense and missense mutations in these four families and in
      three additional families. The disease in these cases therefore should be
      classified as hereditary IF deficiency. Clinically, these patients resembled
      those with typical IGS; radiocobalamin absorption tests had been inconclusive
      regarding the nature of the defect. In the diagnosis of juvenile cobalamin
      deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a
      molecular characterization of the underlying defect and may be the diagnostic
      method of choice.

PMID- 15738393
TI  - MET and MYC cooperate in mammary tumorigenesis.
AB  - In human breast cancer, overexpression of the protooncogene MET is strongly
      associated with poor prognosis and high risk of metastasis. It stands out as a
      reliable prognostic indicator of survival and defines a set of tumors exclusive
      of those that express HER2 or hormone receptors. Studies have shown that
      overexpression of mutant forms of MET cause cancer in mice. However, MET
      mutations have not been found in human breast cancer, and the consequences of
      overexpression of normal MET are unknown. To investigate the role of MET and
      other putative oncogenes in breast cancer, we developed an experimental system
      that involves retroviral delivery of genes into primary mammary epithelial cells,
      followed by transplantation of the transduced cells into mammary fat pads. Using
      this approach, we found that overexpression of wild-type MET leads to the
      development of nonprogressive neoplasms. The lesions progressed to mammary
      adenocarcinoma when a second protooncogene, MYC, was overexpressed, indicating
      that MET and MYC cooperate in mammary tumorigenesis. Both the nonprogressive
      neoplasms and adenocarcinomas display characteristics consistent with
      transformation and expansion of mammary progenitor cells. The approach described
      here should provide a useful model with which to efficiently test effects of
      various genes on tumor development in the breast.

PMID- 15738394
TI  - Identification and functional significance of genes regulated by structurally
      different histone deacetylase inhibitors.
AB  - Histone deacetylase inhibitors (HDACis) inhibit tumor cell growth and survival,
      possibly through their ability to regulate the expression of specific
      proliferative and/or apoptotic genes. However, the HDACi-regulated genes
      necessary and/or sufficient for their biological effects remain undefined. We
      demonstrate that the HDACis suberoylanilide hydroxamic acid (SAHA) and
      depsipeptide regulate a highly overlapping gene set with at least 22% of genes
      showing altered expression over a 16-h culture period. SAHA and depsipeptide
      coordinately regulated the expression of several genes within distinct apoptosis
      and cell cycle pathways. Multiple genes within the Myc, type beta TGF,
      cyclin/cyclin-dependent kinase, TNF, Bcl-2, and caspase pathways were regulated
      in a manner that favored induction of apoptosis and decreased cellular
      proliferation. APAF-1, a gene central to the intrinsic apoptotic pathway, was
      induced by SAHA and depsipeptide and shown to be important, but not essential,
      for HDACi-induced cell death. Overexpression of p16(INK4A) and arrest of cells in
      G(1) can suppress HDACi-mediated apoptosis. Although p16(INK4A) did not affect
      the genome-wide transcription changes mediated by SAHA, a small number of
      apoptotic genes, including BCLXL and B-MYB, were differentially regulated in a
      manner consistent with attenuated HDACi-mediated apoptosis in arrested cells. We
      demonstrate that different HDACi alter transcription of a large and common set of
      genes that control diverse molecular pathways important for cell survival and
      proliferation. The ability of HDACi to target multiple apoptotic and cell
      proliferation pathways may provide a competitive advantage over other
      chemotherapeutic agents because suppression/loss of a single pathway may not
      confer resistance to these agents.

PMID- 15738395
TI  - Climate-driven regime shifts in the biological communities of arctic lakes.
AB  - Fifty-five paleolimnological records from lakes in the circumpolar Arctic reveal
      widespread species changes and ecological reorganizations in algae and
      invertebrate communities since approximately anno Domini 1850. The remoteness of
      these sites, coupled with the ecological characteristics of taxa involved,
      indicate that changes are primarily driven by climate warming through lengthening
      of the summer growing season and related limnological changes. The widespread
      distribution and similar character of these changes indicate that the opportunity
      to study arctic ecosystems unaffected by human influences may have disappeared.

PMID- 15738396
TI  - Mechanism-derived gene expression signatures and predictive biomarkers in
      clinical oncology.

PMID- 15738397
TI  - Comparison of the protein-protein interfaces in the p53-DNA crystal structures:
      towards elucidation of the biological interface.
AB  - p53, the tumor suppressor protein, functions as a dimer of dimers. However, how
      the tetramer binds to the DNA is still an open question. In the crystal
      structure, three copies of the p53 monomers (containing chains A, B, and C) were
      crystallized with the DNA-consensus element. Although the structure provides
      crucial data on the p53-DNA contacts, the active oligomeric state is unclear
      because the two dimeric (A-B and B-C) interfaces present in the crystal cannot
      both exist in the tetramer. Here, we address the question of which of these two
      dimeric interfaces may be more biologically relevant. We analyze the sequence and
      structural properties of the p53-p53 dimeric interfaces and carry out extensive
      molecular dynamics simulations of the crystal structures of the human and mouse
      p53 dimers. We find that the A-B interface residues are more conserved than those
      of the B-C. Molecular dynamics simulations show that the A-B interface can
      provide a stable DNA-binding motif in the dimeric state, unlike B-C. Our results
      indicate that the interface between chains A-B in the p53-DNA complex constitutes
      a better candidate for a stable biological interface, whereas the B-C interface
      is more likely to be due to crystal packing. Thus, they have significant
      implications toward our understanding of DNA binding by p53 as well as p53
      mediated interactions with other proteins.

PMID- 15738398
TI  - Remodeling of the intestine during metamorphosis of Xenopus laevis.
AB  - Thyroid hormone controls remodeling of the tadpole intestine during the climax of
      amphibian metamorphosis. In 8 days, the Xenopus laevis tadpole intestine shortens
      in length by 75%. Simultaneously, the longitudinal muscle fibers contract by
      about the same extent. The radial muscle fibers also shorten as the diameter
      narrows. Many radial fibers undergo programmed cell death. We conclude that
      muscle remodeling and contraction play key roles in the shortening process.
      Shortening is accompanied by a temporary "heaping" of the epithelial cells into
      many layers at climax. Cells that face the lumen undergo apoptosis. By the end of
      metamorphosis, when the epithelium is folded into crypts and villi, the
      epithelium is a single-cell layer once again. Throughout this remodeling, DNA
      replication occurs uniformly throughout the epithelium, as do changes in gene
      expression. The larval epithelial cells as a whole, rather than a subpopulation
      of stem cells, are the progenitors of the adult epithelial cells.

PMID- 15738399
TI  - Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the
      dendritic cells of healthy carriers.
AB  - Human cytomegalovirus (HCMV) persists as a subclinical, lifelong infection in the
      normal human host, but reactivation from latency in immunocompromised subjects
      results in serious disease. Latency and reactivation are defining characteristics
      of the herpesviruses and are key to understanding their biology; however, the
      precise cellular sites in which HCMV is carried and the mechanisms regulating its
      latency and reactivation during natural infection remain poorly understood. Here
      we present evidence, based entirely on direct analysis of material isolated from
      healthy virus carriers, to show that myeloid dendritic cell (DC) progenitors are
      sites of HCMV latency and that their ex vivo differentiation to a mature DC
      phenotype is linked with reactivation of infectious virus resulting from
      differentiation-dependent chromatin remodeling of the viral major immediate-early
      promoter. Thus, myeloid DC progenitors are a site of HCMV latency during natural
      persistence, and there is a critical linkage between their differentiation to DC
      and transcriptional reactivation of latent virus, which is likely to play an
      important role in the pathogenesis of HCMV infection.

PMID- 15738400
TI  - Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas
      reinhardtii identifies orthologs of ciliary disease genes.
AB  - The important role that cilia and flagella play in human disease creates an
      urgent need to identify genes involved in ciliary assembly and function. The
      strong and specific induction of flagellar-coding genes during flagellar
      regeneration in Chlamydomonas reinhardtii suggests that transcriptional profiling
      of such cells would reveal new flagella-related genes. We have conducted a genome
      wide analysis of RNA transcript levels during flagellar regeneration in
      Chlamydomonas by using maskless photolithography method-produced DNA
      oligonucleotide microarrays with unique probe sequences for all exons of the
      19,803 predicted genes. This analysis represents previously uncharacterized whole
      genome transcriptional activity profiling study in this important model organism.
      Analysis of strongly induced genes reveals a large set of known flagellar
      components and also identifies a number of important disease-related proteins as
      being involved with cilia and flagella, including the zebrafish polycystic kidney
      genes Qilin, Reptin, and Pontin, as well as the testis-expressed tubby-like
      protein TULP2.

PMID- 15738401
TI  - Small-molecule-mediated stabilization of familial amyotrophic lateral sclerosis
      linked superoxide dismutase mutants against unfolding and aggregation.
AB  - Familial amyotrophic lateral sclerosis (FALS) is a fatal motor neuron disease
      that is caused by mutations in the gene encoding superoxide dismutase-type 1
      (SOD1). The affected regions of the FALS brain are characterized by aggregated
      SOD1, and the mutations that destabilize SOD1 appear to promote its aggregation
      in vitro. Because dissociation of the native SOD1 dimer is required for its in
      vitro aggregation, we initiated an in silico screening program to find drug-like
      molecules that would stabilize the SOD1 dimer. A potential binding site for such
      molecules at the SOD1 dimer interface was identified, and its importance was
      validated by mutagenesis. About 1.5 million molecules from commercial databases
      were docked at the dimer interface. Of the 100 molecules with the highest
      predicted binding affinity, 15 significantly inhibited in vitro aggregation and
      denaturation of A4V, a FALS-linked variant of SOD1. In the presence of several of
      these molecules, A4V and other FALS-linked SOD1 mutants such as G93A and G85R
      behaved similarly to wild-type SOD1, suggesting that these compounds could be
      leads toward effective therapeutics against FALS.

PMID- 15738402
TI  - Real-time characterization of intermediates in the pathway to open complex
      formation by Escherichia coli RNA polymerase at the T7A1 promoter.
AB  - We have used time-resolved x-ray-generated hydroxyl radical footprinting to
      directly characterize, at single-nucleotide resolution, several intermediates in
      the pathway to open complex formation by Escherichia coli RNA polymerase on the
      T7A1 promoter at 37 degrees C. Three sets of intermediates, corresponding to two
      major conformational changes, are resolved as a function of time; multiple
      conformations equilibrate amongst each other before the next large structural
      change. Analysis of these data in the context of published structural models
      indicates that initial recognition involves interaction of the UP element with
      the alpha-subunit C-terminal domain and binding of the sigma subunit to the -35
      sequence. In the subsequent isomerization step, two complexes with footprints
      extending into the -10 region can be differentiated as the DNA becomes distorted
      during nucleation of strand separation. During the final isomerization step, the
      downstream double helix becomes embedded in the beta/beta' jaws, leading to a
      transcriptionally active complex.

PMID- 15738404
TI  - Chemical genomic profiling to identify intracellular targets of a multiplex
      kinase inhibitor.
AB  - The identification of the kinase or kinases targeted by protein kinase inhibitors
      is a critical challenge in validating their use as therapeutic agents or
      molecular probes. Here, to address this problem, we describe a chemical genomics
      strategy that uses a direct comparison between microarray transcriptional
      signatures elicited by an inhibitor of unknown specificity and those elicited by
      highly specific pharmacological inhibition of engineered candidate kinase
      targets. By using this approach, we have identified two cyclin-dependent kinases,
      Cdk1 and Pho85, as the targets of the inhibitor GW400426 in Saccharomyces
      cerevisiae. We demonstrate that simultaneous inhibition of Cdk1 and Pho85, and
      not inhibition of either kinase alone, by GW400426 controls the expression of
      specific transcripts involved in polarized cell growth, thus revealing a cellular
      process that is uniquely sensitive to the multiplex inhibition of these two
      kinases. Our results suggest that the cellular responses induced by multiplex
      protein kinase inhibitors may be an emergent property that cannot be understood
      fully by considering only the sum of individual inhibitor-kinase interactions.

PMID- 15738403
TI  - Long-range electron transfer.
AB  - Recent investigations have shed much light on the nuclear and electronic factors
      that control the rates of long-range electron tunneling through molecules in
      aqueous and organic glasses as well as through bonds in donor-bridge-acceptor
      complexes. Couplings through covalent and hydrogen bonds are much stronger than
      those across van der Waals gaps, and these differences in coupling between bonded
      and nonbonded atoms account for the dependence of tunneling rates on the
      structure of the media between redox sites in Ru-modified proteins and protein
      protein complexes.

PMID- 15738405
TI  - Extinction dynamics in experimental metapopulations.
AB  - Metapopulation theory provides a framework for understanding population
      persistence in fragmented landscapes and as such has been widely used in
      conservation biology to inform management of fragmented populations. However,
      classical metapopulation theory [Levins, R. (1970) Lect. Notes Math. 2, 75-107]
      ignores metapopulation structure and local population dynamics, both of which may
      affect extinction dynamics. Here, we investigate metapopulation dynamics in
      populations that are subject to different migration rates by using experimental
      metapopulations of the annual plant Cardamine pensylvanica. As predicted by
      classical metapopulation theory, connected populations persisted longer than did
      isolated populations, but the relationship between migration and persistence time
      was nonlinear. Extinction risk sharply increased as the distance between local
      populations increased above a threshold value that was consistent with stochastic
      simulations and calculation of metapopulation capacity [Hanski, I. & Ovaskainen,
      O. (2000) Nature 404, 755-758]. In addition, the most connected metapopulations
      did not have the highest persistence levels. Stochastic simulations indicated an
      increase in extinction risk with the highest migration rates. Moreover,
      calculation of population coherence [Earn, D. J. D., Levin, S. A. & Rohani, P.
      (2000) Science 290, 1360-1364], a metric that predicts synchronous cycles,
      indicated that continuous populations should cycle in phase, resulting in an
      increased extinction risk. Determining empirically the optimal migration level to
      improve survival chances will be challenging for any natural population.
      Migration rates that would not increase migration above the threshold value would
      be ineffectual, but migration rates that would homogenize local densities could
      increase the risk of coherent oscillations and enhance extinction risk.

PMID- 15738406
TI  - Cortical processing of a brightness illusion.
AB  - Several brightness illusions indicate that borders can affect the perception of
      surfaces dramatically. In the Cornsweet illusion, two equiluminant surfaces
      appear to be different in brightness because of the contrast border between them.
      Here, we report the existence of cells in monkey visual cortex that respond to
      such an "illusory" brightness. We find that luminance responsive cells are
      located in color-activated regions (cytochrome oxidase blobs and bridges) of
      primary visual cortex (V1), whereas Cornsweet responsive cells are found
      preferentially in the color-activated regions (thin stripes) of second visual
      area (V2). This colocalization of brightness and color processing within V1 and
      V2 suggests a segregation of contour and surface processing in early visual
      pathways and a hierarchy of brightness information processing from V1 to V2 in
      monkeys.

PMID- 15738407
TI  - Culturing at atmospheric oxygen levels impacts lymphocyte function.
AB  - To determine whether culturing peripheral blood mononuclear cells at atmospheric
      oxygen levels skews responses in comparison with culturing lymphocytes at
      physiologic oxygen levels, we cultured peripheral blood mononuclear cells at 5%,
      10%, and atmospheric (20%) gas-phase oxygen for 5 days. We found that incubator
      oxygen levels influenced lymphocyte proliferation stimulated by two commonly used
      stimuli: Con A and antibodies that crosslink surface CD3 and CD28 to mimic
      antigen presentation. In both cases, proliferation increased as gas-phase oxygen
      levels increased. In contrast, oxygen levels did not influence proliferation
      stimulated by phytohemagglutinin, another commonly used mitogen. Similarly,
      oxygen levels did not impact cell viability in unstimulated cultures. Thus, we
      conclude that the influence of oxygen levels on proliferation depends on the
      stimulus, and, most importantly from the standpoint of immune responses,
      culturing cells at atmospheric rather than physiologic oxygen levels results in
      significantly increased proliferation responses to the CD3/CD28 crosslinking, a
      proliferation stimulus commonly used to mimic T cell antigen receptor signaling.

PMID- 15738409
TI  - Protein dynamics and electron transfer: electronic decoherence and non-Condon
      effects.
AB  - We compute the autocorrelation function of the donor-acceptor tunneling matrix
      element <T(DA)(t)T(DA)(0)> for six Ru-azurin derivatives. Comparison of this
      decay time to the decay time of the time-dependent Franck-Condon factor {computed
      by Rossky and coworkers [Lockwood, D. M., Cheng, Y.-K. & Rossky, P. J. (2001)
      Chem. Phys. Lett. 345, 159-165]} reveals the extent to which non-Condon effects
      influence the electron-transfer rate. <T(DA)(t)T(DA)(0)> is studied as a function
      of donor-acceptor distance, tunneling pathway structure, tunneling energy, and
      temperature to explore the structural and dynamical origins of non-Condon
      effects. For azurin, the correlation function is remarkably insensitive to
      tunneling pathway structure. The decay time is only slightly shorter than it is
      for solvent-mediated electron transfer in small organic molecules and originates,
      largely, from fluctuations of valence angles rather than bond lengths.

PMID- 15738408
TI  - Automated microscope system for determining factors that predict neuronal fate.
AB  - Unraveling cause-and-effect relationships in the nervous system is challenging
      because some biological processes begin stochastically, take a significant amount
      of time to unfold, and affect small neuronal subpopulations that can be difficult
      to isolate and measure. Single-cell approaches are slow, subject to user bias,
      and sometimes too laborious to achieve sample sizes large enough to detect
      important effects. Here, we describe an automated imaging and analysis system
      that enables us to follow the fates of individual cells and intracellular
      proteins over time. Observations can be quantified in a high-throughput manner
      with minimal user bias. We have adapted survival analysis methods to determine
      whether and how factors measured during longitudinal analysis predict a
      particular biological outcome. The ability to monitor complex processes at single
      cell resolution quickly, quantitatively, and over long intervals should have wide
      applications for biology.

PMID- 15738410
TI  - Wire-like charge transport at near constant bridge energy through fluorene
      oligomers.
AB  - The study of photoinitiated electron transfer in donor-bridge-acceptor molecules
      has helped elucidate the distance dependence of electron transfer rates and
      behavior of various electron transfer mechanisms. In all reported cases, the
      energies of the bridge electronic states involved in the electron transfer change
      dramatically as the length of the bridge is varied. We report here, in contrast,
      an instance in which the length of the bridge, and therefore the distance over
      which the electron is transferred, can be varied without significantly changing
      the energies of the relevant bridge states. A series of donor-bridge-acceptor
      molecules having phenothiazine (PTZ) donors, 2,7-oligofluorene (FL(n)) bridges,
      and perylene-3,4:9,10-bis(dicarboximide) (PDI) acceptors was studied.
      Photoexcitation of PDI to its lowest excited singlet state results in oxidation
      of PTZ via the FL(n) bridge. In toluene, the rate constants for both charge
      separation and recombination as well as the energy levels of the relevant
      FL(n)(+.) bridge states for n = 1-4 are only weakly distance dependent. After the
      initial photo-generation of (1)(PTZ(+.)-FL(n)-PDI(-.)), radical pair intersystem
      crossing results in formation of (3)(PTZ(+.)-FL(n)-PDI(-.)) that recombines to
      give (3.)PDI. The dependence of the (3.)PDI yield on an applied magnetic field
      shows a resonance, which gives the singlet-triplet splitting, 2J, of the radical
      ion pair. The magnitude of 2J directly monitors the contribution of coherent
      charge transfer (superexchange) to the overall electron transfer rate. These data
      show that charge recombination through FL(n) is dominated by incoherent hopping
      at long distances.

PMID- 15738411
TI  - Differential influence of dynamic processes on forward and reverse electron
      transfer across a protein-protein interface.
AB  - We propose that the forward and reverse halves of a flash-induced protein-protein
      electron transfer (ET) photocycle should exhibit differential responses to
      dynamic interconversion of configurations when the most stable configuration is
      not the most reactive, because the reactants exist in different initial
      configurations: the flash-photoinitiated forward ET process begins with the
      protein partners in an equilibrium ensemble of configurations, many of which have
      little or no reactivity, whereas the reactant of the thermal back ET (the charge
      separated intermediate) is formed in a nonequilibrium, "activated" protein
      configuration. We report evidence for this proposal in measurements on (i) mixed
      metal hemoglobin hybrids, (ii) the complex between cytochrome c peroxidase and
      cytochrome c, and (iii and iv) the complexes of myoglobin and isolated hemoglobin
      alpha-chains with cytochrome b(5). For all three systems, forward and reverse ET
      does respond differently to modulation of dynamic processes; further, the
      response to changes in viscosity is different for each system.

PMID- 15738412
TI  - Ultrasensitivity and noise propagation in a synthetic transcriptional cascade.
AB  - The precise nature of information flow through a biological network, which is
      governed by factors such as response sensitivities and noise propagation, greatly
      affects the operation of biological systems. Quantitative analysis of these
      properties is often difficult in naturally occurring systems but can be greatly
      facilitated by studying simple synthetic networks. Here, we report the
      construction of synthetic transcriptional cascades comprising one, two, and three
      repression stages. These model systems enable us to analyze sensitivity and noise
      propagation as a function of network complexity. We demonstrate experimentally
      steady-state switching behavior that becomes sharper with longer cascades. The
      regulatory mechanisms that confer this ultrasensitive response both attenuate and
      amplify phenotypical variations depending on the system's input conditions.
      Although noise attenuation allows the cascade to act as a low-pass filter by
      rejecting short-lived perturbations in input conditions, noise amplification
      results in loss of synchrony among a cell population. The experimental results
      demonstrating the above network properties correlate well with simulations of a
      simple mathematical model of the system.

PMID- 15738413
TI  - Identification of viral genes essential for replication of murine gamma
      herpesvirus 68 using signature-tagged mutagenesis.
AB  - Gamma-herpesviruses, Epstein-Barr virus, and Kaposi's sarcoma-associated
      herpesvirus are important human pathogens, because they are involved in tumor
      development. Murine gamma-herpesvirus-68 (MHV-68 or gammaHV-68) has emerged as a
      small animal model system for the study of gamma-herpesvirus pathogenesis and
      host-virus interactions. To identify the genes required for viral replication in
      vitro and in vivo, we generated 1,152 mutants using signature-tagged transposon
      mutagenesis on an infectious bacterial artificial chromosome of MHV-68. Almost
      every ORF was mutated by random insertion. For each ORF, a mutant with an
      insertion proximal to the N terminus of each ORF was examined for the ability to
      grow in fibroblasts. Our results indicate that 41 genes are essential for in
      vitro growth, whereas 26 are nonessential and 6 attenuated. Replication-competent
      mutants were pooled to infect mice, which led to the discovery of ORF 54 being
      important for MHV-68 to replicate in the lung. This genetic analysis of a tumor
      associated herpesvirus at the whole genome level validates signature-tagged
      transposon mutagenesis screening as an effective genetic system to identify
      important virulent genes in vivo and define interactions with the host immune
      system.

PMID- 15738414
TI  - Architecture of the bacteriophage T4 primosome: electron microscopy studies of
      helicase (gp41) and primase (gp61).
AB  - Replication of DNA requires helicase and primase activities as part of a
      primosome assembly. In bacteriophage T4, helicase and primase are separate
      polypeptides for which little structural information is available and whose
      mechanism of association within the primosome is not yet understood. Three
      dimensional structural information is provided here by means of reconstructions
      from electron microscopic images. Structures have been calculated for complexes
      of each of these proteins with ssDNA in the presence of MgATPgammaS. Both the
      helicase (gp41) and primase (gp61) complexes are asymmetric hexagonal rings. The
      gp41 structure suggests two distinct forms that have been termed "open" and
      "closed." The gp61 structure is clearly a six-membered ring, which may be a
      trimer of dimers or a traditional hexamer of monomers. This structure provides
      conclusive evidence for an oligomeric primase-to-ssDNA stoichiometry of 6:1.

PMID- 15738415
TI  - Accumulation of miR-155 and BIC RNA in human B cell lymphomas.
AB  - We show that the microRNA miR-155 can be processed from sequences present in BIC
      RNA, a spliced and polyadenylated but non-protein-coding RNA that accumulates in
      lymphoma cells. The precursor of miR-155 is likely a transient spliced or
      unspliced nuclear BIC transcript rather than accumulated BIC RNA, which is
      primarily cytoplasmic. By using a sensitive and quantitative assay, we find that
      clinical isolates of several types of B cell lymphomas, including diffuse large B
      cell lymphoma (DLBCL), have 10- to 30-fold higher copy numbers of miR-155 than do
      normal circulating B cells. Similarly, the quantities of BIC RNA are elevated in
      lymphoma cells, but ratios of the amounts of the two RNAs are not constant,
      suggesting that the level of miR-155 is controlled by transcription and
      processing. Significantly higher levels of miR-155 are present in DLBCLs with an
      activated B cell phenotype than with the germinal center phenotype. Because
      patients with activated B cell-type DLBCL have a poorer clinical prognosis,
      quantification of this microRNA may be diagnostically useful.

PMID- 15738416
TI  - Proton binding within a membrane protein by a protonated water cluster.
AB  - Proton transfer is crucial for many enzyme reactions. Here, we show that in
      addition to protonatable amino acid side chains, water networks could constitute
      proton-binding sites in proteins. A broad IR continuum absorbance change during
      the proton pumping photocycle of bacteriorhodopsin (bR) indicates most likely
      deprotonation of a protonated water cluster at the proton release site close to
      the surface. We investigate the influence of several mutations on the proton
      release network and the continuum change, to gain information about the location
      and extent of the protonated water network and to reveal the participating
      residues necessary for its stabilization. We identify a protonated water cluster
      consisting in total of one proton and about five water molecules surrounded by
      six side chains and three backbone groups (Tyr-57, Arg-82, Tyr-83, Glu-204, Glu
      194, Ser-193, Pro-77, Tyr-79, and Thr-205). The observed perturbation of proton
      release by many single-residue mutations is now explained by the influence of
      numerous side chains on the protonated H bonded network. In situ
      hydrogen/deuterium exchange Fourier transform IR measurements of the bR ground
      state, show that the proton of the release group becomes localized on Glu-204 and
      Asp-204 in the ground state of the mutants E194D and E204D, respectively, even
      though it is delocalized in the ground state of wild-type bR. Thus, the release
      mechanism switches between the wild-type and mutated proteins from a delocalized
      to a localized proton-binding site.

PMID- 15738417
TI  - Transdifferentiation of corneal epithelium into epidermis occurs by means of a
      multistep process triggered by dermal developmental signals.
AB  - Differentiated cells of the corneal epithelium are converted to hair, along with
      their associated stem cells, then interfollicular epidermis, by means of a
      multistep process triggered by dermal developmental signals. The committed basal
      cells of the adult corneal epithelium dedifferentiate under the control of
      signals from an associated embryonic hair-forming dermis, likely Wnts, and revert
      to a limbal basal cell phenotype. This initial process involves the down
      regulation of Pax6 and the loss of expression of corneal-specific keratins and
      the induction of basal keratinocyte markers. These dedifferentiated cells are
      able to reinduce dermal condensations, which in turn induce the formation of hair
      follicles from cells that have lost Pax6 expression, by means of a Noggin
      dependent mechanism. An epidermis is subsequently formed by cells derived from
      the newly segregated hair stem cells.

PMID- 15738418
TI  - Regulation of heterogenous nuclear ribonucleoprotein A1 transport by
      phosphorylation in cells stressed by osmotic shock.
AB  - Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an alternative splicing
      factor that is mainly nuclear, although it shuttles rapidly between nuclear and
      cytoplasmic compartments. Cells stressed by osmotic shock (OSM) activate the
      mitogen-activated protein kinase kinase(3/6)-p38 signaling pathway, which in turn
      results in accumulation of hnRNP A1 in the cytoplasm. This effect modulates
      alternative splicing regulation in vivo and correlates with increased hnRNP A1
      phosphorylation. We have characterized the molecular mechanism involved in the
      cytoplasmic accumulation of hnRNP A1 in NIH 3T3 cells subjected to OSM. This
      treatment results in serine-specific phosphorylation within a C-terminal peptide,
      dubbed the "F-peptide," which is adjacent to the M9 motif that mediates
      bidirectional transport of hnRNP A1. Analysis of mutants in which the F-peptide
      serines were replaced by aspartic acids or alanines showed that F-peptide
      phosphorylation is required for the subcellular redistribution of hnRNP A1 in
      cells subjected to OSM. Furthermore, F-peptide phosphorylation modulates the
      interaction of hnRNP A1 with transportin Trn1. Our findings suggest that the
      phosphorylation of F-peptide by cell-signaling pathways regulates the rate of
      hnRNP A1 nuclear import.

PMID- 15738420
TI  - Disrupting integrin transmembrane domain heterodimerization increases ligand
      binding affinity, not valency or clustering.
AB  - Residues important in the interaction between the 23-residue transmembrane (TM)
      domains of the integrin alpha(IIb)- and beta(3)-subunits were identified by
      mutating each non-Leu residue to Leu. Leu substitutions of alpha(IIb) at G972,
      G976, and T981, and of beta(3) at I693 and G708, increased ligand binding.
      Substitutions with other amino acids at alpha(IIb)G972 and beta(3)G708 could also
      increase ligand binding. The results are consistent with and extend the helical
      interface between the integrin alpha- and beta-subunit TM domains previously
      defined by cysteine scanning and disulfide bond formation. We differentiated
      between affinity- and valency-based modes of activation by TM domain mutations.
      The mutant alpha(IIb) W967C forms disulfide-linked alpha(IIb)-subunits within an
      (alpha(IIb)beta(3))(2) tetramer. This tetramer behaved as an ideal model for the
      valency mode of regulation, because it exhibited significantly increased binding
      to multivalent but not monovalent ligands and basally retained the bent
      conformation. By contrast, the activating Leu mutants showed increased binding to
      the monovalent, ligand-mimetic PAC-1 Fab and increased exposure of ligand-induced
      binding site (LIBS) epitopes, suggesting that they partially adopt an extended
      conformation. Furthermore, the previously described beta(3)G708N mutation in
      Chinese hamster ovary cells enhanced ligand binding affinity, not valency, and
      did not alter cell-surface clustering as defined by confocal microscopy. Our
      studies provide evidence that disrupting the integrin heterodimeric TM helix
      helix interface activates ligand binding mainly by increasing the monomeric
      affinity for ligand, but not the receptor valency, i.e., clustering.

PMID- 15738419
TI  - Perinatal exposure to nicotine causes deficits associated with a loss of
      nicotinic receptor function.
AB  - We investigated the role played by beta2-containing neuronal nicotinic receptors
      [nicotinic acetylcholine receptors (nAChRs)] in mediating nicotine's side effects
      in the fetus and newborn. Pregnant WT and mutant mice lacking the beta2 nAChR
      subunit were implanted with osmotic minipumps that delivered either water or a
      controlled dose of nicotine. Subsequently, we compared the development of the
      sympathoadrenal system and breathing and arousal reflexes of offspring shortly
      after birth, a period of increased vulnerability to nicotine exposure. Newborn WT
      pups exposed to nicotine exhibited all of the deficits associated with maternal
      tobacco and nicotine use, and linked to poor neonatal outcome: growth
      restriction, unstable breathing, and impaired arousal and catecholamine
      biosynthesis. Remarkably similar deficits were detected in pups lacking beta2
      containing nAChRs. Loss-of-function of these nAChRs consequently reproduces with
      astonishing fidelity many of the abnormalities caused by perinatal nicotine
      exposure. We propose that the underlying mechanisms of nicotine's detrimental
      side effects on a range of crucial defensive reflexes involve loss of function of
      nAChR subtypes, possibly via activity-dependent desensitization.

PMID- 15738421
TI  - Protein-DNA charge transport: redox activation of a DNA repair protein by guanine
      radical.
AB  - DNA charge transport (CT) chemistry provides a route to carry out oxidative DNA
      damage from a distance in a reaction that is sensitive to DNA mismatches and
      lesions. Here, DNA-mediated CT also leads to oxidation of a DNA-bound base
      excision repair enzyme, MutY. DNA-bound Ru(III), generated through a flash/quench
      technique, is found to promote oxidation of the [4Fe-4S](2+) cluster of MutY to
      [4Fe-4S](3+) and its decomposition product [3Fe-4S](1+). Flash/quench experiments
      monitored by EPR spectroscopy reveal spectra with g = 2.08, 2.06, and 2.02,
      characteristic of the oxidized clusters. Transient absorption spectra of
      poly(dGC) and [Ru(phen)(2)dppz](3+) (dppz = dipyridophenazine), generated in
      situ, show an absorption characteristic of the guanine radical that is depleted
      in the presence of MutY with formation instead of a long-lived species with an
      absorption at 405 nm; we attribute this absorption also to formation of the
      oxidized [4Fe-4S](3+) and [3Fe-4S](1+) clusters. In ruthenium-tethered DNA
      assemblies, oxidative damage to the 5'-G of a 5'-GG-3' doublet is generated from
      a distance but this irreversible damage is inhibited by MutY and instead EPR
      experiments reveal cluster oxidation. With ruthenium-tethered assemblies
      containing duplex versus single-stranded regions, MutY oxidation is found to be
      mediated by the DNA duplex, with guanine radical as an intermediate oxidant;
      guanine radical formation facilitates MutY oxidation. A model is proposed for the
      redox activation of DNA repair proteins through DNA CT, with guanine radicals,
      the first product under oxidative stress, in oxidizing the DNA-bound repair
      proteins, providing the signal to stimulate DNA repair.

PMID- 15738422
TI  - Regulation of platelet granule exocytosis by S-nitrosylation.
AB  - Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and
      by mechanisms that are not completely defined. Platelet activation includes
      exocytosis of platelet granules, releasing mediators that regulate interactions
      between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in
      part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles
      complexes of soluble NSF attachment protein receptors. We now demonstrate that NO
      inhibits exocytosis of dense granules, lysosomal granules, and alpha-granules
      from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO
      synthase show increased rolling on venules, increased thrombosis in arterioles,
      and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by
      which NO regulates thrombosis.

PMID- 15738423
TI  - Structural and mechanistic analysis of two prolyl endopeptidases: role of
      interdomain dynamics in catalysis and specificity.
AB  - Prolyl endopeptidases (PEPs) are a unique class of serine proteases with
      considerable therapeutic potential for the treatment of celiac sprue. The crystal
      structures of two didomain PEPs have been solved in alternative configurations,
      thereby providing insights into the mode of action of these enzymes. The
      structure of the Sphingomonas capsulata PEP, solved and refined to 1.8-A
      resolution, revealed an open configuration of the active site. In contrast, the
      inhibitor-bound PEP from Myxococcus xanthus was crystallized (1.5-A resolution)
      in a closed form. Comparative analysis of the two structures highlights a
      critical role for the domain interface in regulating interdomain dynamics and
      substrate specificity. Structure-based mutagenesis of the M. xanthus PEP confirms
      an important role for several interfacial residues. A salt bridge between Arg-572
      and Asp-196/Glu-197 appears to act as a latch for opening or closing the didomain
      enzyme, and Arg-572 and Ile-575 may also help secure the incoming peptide
      substrate to the open form of the enzyme. Arg-618 and Asp-145 are responsible for
      anchoring the invariant proline residue in the active site of this postproline
      cleaving enzyme. A model is proposed for the docking of a representative
      substrate PQPQLPYPQPQLP in the active site, where the N-terminal substrate
      residues interact extensively with the catalytic domain, and the C-terminal
      residues stretch into the propeller domain. Given the promise of the M. xanthus
      PEP as an oral therapeutic enzyme for treating celiac sprue, our results provide
      a strong foundation for further optimization of the PEP's clinically useful
      features.

PMID- 15738424
TI  - Theta oscillations and sensorimotor performance.
AB  - Performance and cognitive effort in humans have recently been related to
      amplitude and multisite coherence of alpha (7-12 Hz) and theta (4-7 Hz) band
      electroencephalogram oscillations. I examined this phenomenon in rats by using
      theta band oscillations of the local field potential to signify sniffing as a
      sensorimotor process. Olfactory bulb (OB) theta oscillations are coherent with
      those in the dorsal hippocampus (HPC) during odor sniffing in a two-odor
      olfactory discrimination task. Coherence is restricted to the high-frequency
      theta band (6-12 Hz) associated with directed sniffing in the OB and type 1 theta
      in the HPC. Coherence and performance fluctuate on a time scale of several
      minutes. Coherence magnitude is positively correlated with performance in the two
      odor condition but not in extended runs of single odor conditional-stimulus
      positive trials. Simultaneous with enhanced OB-HPC theta band coherence during
      odor sniffing is a significant decrease in lateral entorhinal cortex (EC)-HPC and
      OB-EC coherence, suggesting that linkage of the olfactory and hippocampal theta
      rhythms is not through the synaptic relay from OB to HPC in the lateral EC. OB
      HPC coupling at the sniffing frequency is proposed as a mechanism underlying
      olfactory sensorimotor effort as a cognitive process.

PMID- 15738426
TI  - Interprotein electron transfer from cytochrome c2 to photosynthetic reaction
      center: tunneling across an aqueous interface.
AB  - Interprotein electron transfer (ET) reactions play an important role in
      biological energy conversion processes. One of these reactions, the ET between
      cytochrome c(2) (cyt) and reaction center from photosynthetic bacteria, is the
      focus of this theoretical study. The changes in the ET rate constant at fixed
      distances during the association process were calculated as the cyt moved from
      the electrostatically stabilized encounter complex to the bound state having
      short range van der Waals contacts in the tunneling region. Multiple
      conformations of the protein were generated by molecular dynamics simulations
      including explicit water molecules. For each of these conformations, the ET rate
      was calculated by using the Pathways model. The ET rate increased smoothly as the
      cyt approached from the encounter complex to the bound state, with a tunneling
      decay factor beta = 1.1 A(-1). This relatively efficient coupling between redox
      centers is due to the ability of interfacial water molecules to form multiple
      strong hydrogen bonding pathways connecting tunneling pathways on the surfaces of
      the two proteins. The ET rate determined for the encounter complex ensemble of
      states is only about a factor of 100 slower than that of the bound state (tau =
      100 micros, compared with 1 micros), because of fluctuations of the cyt within
      the encounter complex ensemble through configurations having strong tunneling
      pathways. The ET rate for the encounter complex is in agreement with rates
      observed in mutant reaction centers modified to remove shortrange hydrophobic
      interactions, suggesting that in this case, ET occurs within the solvent
      separated, electrostatically stabilized encounter complex.

PMID- 15738425
TI  - Inactivation of liver X receptor beta leads to adult-onset motor neuron
      degeneration in male mice.
AB  - Male mice with inactivated liver X receptor (LXR) beta suffer from adult-onset
      motor neuron degeneration. By 7 months of age, motor coordination is impaired,
      and this condition is associated with lipid accumulation and loss of motor
      neurons in the spinal cord, together with axonal atrophy and astrogliosis.
      Several of these features are reminiscent of the neuropathological signs of
      chronic motor neuron disease such as amyotrophic lateral sclerosis. Because the
      LXRs are important for cholesterol and lipid metabolism, we speculate that
      absence of LXRbeta leads to pathological accumulation of sterols and lipids that
      may themselves be neurotoxic or may modulate intracellular pathways and thereby
      predispose motor neurons to degeneration.

PMID- 15738427
TI  - Three-dimensional reconstruction of the dynactin complex by single-particle image
      analysis.
AB  - Dynactin is a large complex of at least nine distinct proteins that co-complexes
      with cytoplasmic dynein within cells, where it plays a major role as a regulator
      of the motor's function. Owing to its large size and complexity, relatively
      little is known about dynactin's 3D structure or the structural basis of its
      function. Use of single-particle image analysis techniques has enabled us to
      produce the first 3D reconstruction of the dynactin complex, to a resolution of 3
      nm. The actin-related protein (Arp) backbone of the filament has been clearly
      visualized. Fitting of models of the Arp backbone showed that it consists of 10
      subunits. Additional mass, not part of the Arp backbone, was also seen. A
      preliminary fitting of the capping protein CapZ structure into our 3D
      reconstruction of the dynactin complex suggests that it is optimally placed to
      perform its proposed function as a stabilizer of the Arp1 backbone and gives
      clues as to likely interaction points between the capping protein and Arp
      subunits. The results provide the first detailed visualization of the dynactin
      complex and shed light on the mode of interaction between several of its
      constituent proteins and their possible functions.

PMID- 15738429
TI  - Standing up for the medical rights of asylum seekers.

PMID- 15738430
TI  - Autonomy in medical ethics after O'Neill.
AB  - Following the influential Gifford and Reith lectures by Onora O'Neill, this paper
      explores further the paradigm of individual autonomy which has been so dominant
      in bioethics until recently and concurs that it is an aberrant application and
      that conceptions of individual autonomy cannot provide a sufficient and
      convincing starting point for ethics within medical practice. We suggest that
      revision of the operational definition of patient autonomy is required for the
      twenty first century. We follow O'Neill in recommending a principled version of
      patient autonomy, which for us involves the provision of sufficient and
      understandable information and space for patients, who have the capacity to make
      a settled choice about medical interventions on themselves, to do so responsibly
      in a manner considerate to others. We test it against the patient-doctor
      relationship in which each fully respects the autonomy of the other based on an
      unspoken covenant and bilateral trust between the doctor and patient. Indeed we
      consider that the dominance of the individual autonomy paradigm harmed that
      relationship. Although it seems to eliminate any residue of medical paternalism
      we suggest that it has tended to replace it with an equally (or possibly even
      more) unacceptable bioethical paternalism. In addition it may, for example, lead
      some doctors to consider mistakenly that unthinking acquiescence to a requested
      intervention against their clinical judgement is honouring "patient autonomy"
      when it is, in fact, abrogation of their duty as doctors.

PMID- 15738428
TI  - Nuclear processing and export of microRNAs in Arabidopsis.
AB  - In mammalian cells, the nuclear export receptor, Exportin 5 (Exp5), exports pre
      microRNAs (pre-miRNAs) as well as tRNAs into the cytoplasm. In this study, we
      examined the function of HASTY (HST), the Arabidopsis ortholog of Exp5, in the
      biogenesis of miRNAs and tRNAs. In contrast to mammals, we found that miRNAs
      exist as single-stranded 20- to 21-nt molecules in the nucleus in Arabidopsis.
      This observation is consistent with previous studies indicating that proteins
      involved in miRNA biogenesis are located in the nucleus in Arabidopsis. Although
      miRNAs exist in the nucleus, a majority accumulate in the cytoplasm.
      Interestingly, loss-of-function mutations in HST reduced the accumulation of most
      miRNAs but had no effect on the accumulation of tRNAs and endogenous small
      interfering RNAs, or on transgene silencing. In contrast, a mutation in PAUSED
      (PSD), the Arabidopsis ortholog of the tRNA export receptor, Exportin-t,
      interfered with the processing of tRNA-Tyr but did not affect the accumulation or
      nuclear export of miRNAs. These results demonstrate that HST and PSD do not share
      RNA cargos in nuclear export and strongly suggest that there are multiple nuclear
      export pathways for these small RNAs in Arabidopsis.

PMID- 15738431
TI  - Physicians' evaluations of patients' decisions to refuse oncological treatment.
AB  - OBJECTIVE: To gain insight into the standards of rationality that physicians use
      when evaluating patients' treatment refusals. DESIGN OF THE STUDY: Qualitative
      design with in depth interviews. PARTICIPANTS: The study sample included 30
      patients with cancer and 16 physicians (oncologists and general practitioners).
      All patients had refused a recommended oncological treatment. RESULTS: Patients
      base their treatment refusals mainly on personal values and/or experience.
      Physicians mainly emphasise the medical perspective when evaluating patients'
      treatment refusals. From a medical perspective, a patient's treatment refusal
      based on personal values and experience is generally evaluated as irrational and
      difficult to accept, especially when it concerns a curative treatment. Physicians
      have a different attitude towards non-curative treatments and have less
      difficulty accepting a patient's refusal of these treatments. Thus, an important
      factor in the physician's evaluation of a treatment refusal is whether the
      treatment refused is curative or non-curative. CONCLUSION: Physicians mainly use
      goal oriented and patients mainly value oriented rationality, but in the case of
      non-curative treatment refusal, physicians give more emphasis to value oriented
      rationality. A consensus between the value oriented approaches of patient and
      physician may then emerge, leading to the patient's decision being understood and
      accepted by the physician. The physician's acceptance is crucial to his or her
      attitude towards the patient. It contributes to the patient's feeling free to
      decide, and being understood and respected, and thus to a better physician
      patient relationship.

PMID- 15738432
TI  - Capacity, consent, and selection bias in a study of delirium.
AB  - OBJECTIVES: To investigate whether different methods of obtaining informed
      consent affected recruitment to a study of delirium in older, medically ill
      hospital inpatients. DESIGN: Open randomised study. SETTING: Acute medical
      service for older people in an inner city teaching hospital. PARTICIPANTS:
      Patients 70 years or older admitted to the unit within three days of hospital
      admission randomised into two groups. INTERVENTION: Attempted recruitment of
      subjects to a study of the natural history of delirium. This was done by either
      (a) a formal test of capacity, followed by either a request for consent or an
      attempt at obtaining assent from a proxy, or (b) a combined informal
      capacity/consent process. MAIN OUTCOME MEASURES: Prevalence and severity of
      delirium, and, as case mix measures, length of hospital stay and destination on
      discharge. RESULTS: Recruitment of subjects through establishing formal capacity
      and then informed consent was less successful (43.9% v 74% of those approached)
      and, compared with those recruited through the usual combined capacity/consent
      approach, yielded a sample with less cognitive impairment, lower severity of
      delirium, lower probability of case note diagnosis of delirium and lower rate of
      entering a care home. CONCLUSIONS: Methods of obtaining informed consent may
      significantly influence the case mix of subjects recruited to a study of
      delirium. Stringent testing of capacity may exclude patients with delirium from
      studies, thus rendering findings less generalizable. A different method is
      necessary to achieve an ethical balance between respecting autonomy through
      obtaining adequate informed consent and avoiding sample bias.

PMID- 15738433
TI  - Pharmacogenetics, ethical issues: review of the Nuffield Council on Bioethics
      Report.
AB  - In September this year the Nuffield Council on Bioethics held a meeting to
      disclose and discuss the main findings of their newly published report on the
      ethical issues associated with developments in pharmacogenetics research. The
      basics of pharmacogenetics science is briefly outlined, and then the extent to
      which the report was successful in addressing (or at least highlighting) the
      attendant social, ethical, and policy implications of pharmacogenetics research
      is evaluated.

PMID- 15738435
TI  - Ethical dilemmas: feeding back results to members of a longitudinal cohort study.

PMID- 15738434
TI  - Sham surgery controls are mitigated trolleys.
AB  - Debate continues about the ethics of sham surgery controls. The most powerful
      argument for sham surgery controls is that rigorous experiments are needed to
      demonstrate safety and efficacy of surgical procedures. Without such experiments,
      there is danger of adopting worthless procedures in clinical practice. Opponents
      of sham surgery controls argue that sham surgery constitutes unacceptable
      violation of the rights of research subjects. Recent philosophical discussion has
      used two thought experiments-the transplant case and the trolley problem-to
      explore the circumstances under which individuals may be harmed to benefit a
      larger group. The transplant case is felt to exemplify circumstances that forbid
      harming some to benefit a larger group while the trolley problem exemplifies
      circumstances that permit harming some to benefit others. I argue that sham
      surgery controls satisfy criteria derived from the trolley problem and are
      morally permissible.

PMID- 15738436
TI  - To have or to be: ways of caregiving identified during recovery from the
      earthquake disaster in Taiwan.
AB  - The aim of this article is to report the results of therapy sessions conducted
      with survivors of an earthquake that struck Luku Township in Nantou County,
      central Taiwan, in September 1999. The sessions explored survivors' feelings,
      interactions, and interpretations of the crisis, as well as their roles in post
      earthquake relief efforts. The participants were teachers and administrators from
      four primary schools. The results indicated three distinct forms of caring,
      namely: encumbered caring, connected caring, and reflected caring. The findings
      were used to construct a framework for caregiver self-monitoring. They also
      suggest that therapy groups provide an inner space that self-regulates the
      frustrations arising from this type of experience, for both caregivers and
      survivors. The intrasubjective and intersubjective dialogues within the groups
      are essentially reflective practices for improving services and generating new
      knowledge about medical ethics.

PMID- 15738437
TI  - The bioethical principles and Confucius' moral philosophy.
AB  - This paper examines whether the modern bioethical principles of respect for
      autonomy, beneficence, non-maleficence, and justice proposed by Beauchamp and
      Childress are existent in, compatible with, or acceptable to the leading Chinese
      moral philosophy-the ethics of Confucius. The author concludes that the moral
      values which the four prima facie principles uphold are expressly identifiable in
      Confucius' teachings. However, Confucius' emphasis on the filial piety, family
      values, the "love of gradation", altruism of people, and the "role specified
      relation oriented ethics" will inevitably influence the "specification" and
      application of these bioethical principles and hence tend to grant "beneficence"
      a favourable position that diminishes the respect for individual rights and
      autonomy. In contrast, the centrality of respect for autonomy and its stance of
      "first among equals" are more and more stressed in Western liberal viewpoints.
      Nevertheless, if the Confucian "doctrine of Mean" (chung-yung) and a balanced
      "two dimensional personhood" approach are properly employed, this will require
      both theorists and clinicians, who are facing medical ethical dilemmas, of
      searching to attain due mean out of competing moral principles thus preventing
      "giving beneficence a priority" or "asserting autonomy must triumph".

PMID- 15738438
TI  - Ethical issues in funding orphan drug research and development.
AB  - This essay outlines the moral dilemma of funding orphan drug research and
      development. To date, ethical aspects of priority setting for research funding
      have not been an issue of discussion in the bioethics debate. Conflicting moral
      obligations of beneficence and distributive justice appear to demand very
      different levels of funding for orphan drug research. The two types of orphan
      disease, rare diseases and tropical diseases, however, present very different
      ethical challenges to questions about allocation of research funds. The dilemma
      is analysed considering utilitarian and rights based theories of justice and
      moral obligations of non-abandonment and a professional obligation to advance
      medical science. The limitations of standard economic evaluation tools and other
      priority setting tools used to inform health policy decision makers on research
      funding decisions are outlined.

PMID- 15738439
TI  - The physician and prison hunger strikes: reflecting on the experience in Turkey.
AB  - The medical ethics of a physician's relationship with a prisoner who is
      participating in a collective hunger strike has become a major public,
      professional, and governmental concern in The Republic of Turkey. This article
      examines the Turkish experience and debate about physician ethics during prison
      hunger strikes. It is hoped that this analysis will be of use to those
      formulating policy in similar situations.

PMID- 15738440
TI  - Will international human rights subsume medical ethics? Intersections in the
      UNESCO Universal Bioethics Declaration.
AB  - The International Bioethics Committee (IBC) of the United Nations Educational,
      Scientific and Cultural Organisation (UNESCO) is currently drafting a Universal
      Bioethics Declaration ("the declaration"). The content and even the name of the
      declaration has yet to be finalized, but it is expected to range widely over
      human and non-human bioethics. It appears likely to include many articles
      directly related to medical ethics. The declaration may well evolve, like the
      Universal Declaration of Human Rights, into a component of international
      customary law, or be the precursor to an International Convention on Bioethics.
      This article discusses whether this process will facilitate bioethics and, in
      particular, medical ethics, being subsumed by the normative system of
      international human rights.

PMID- 15738441
TI  - Blinkered objections to bioethics: a response to Benatar.
AB  - In a recent commentary, S R Benatar criticised the debates over organ donation
      and kidney selling for being located within a "narrow and inadequate framework".
      Benatar levels four charges against those who engage in the current organs
      debate: that they myopically focus on saving lives; that they accept the
      dominance of market orientated approaches to health care; that they reify
      individualism, and that they engage in limited moral arguments. Given the
      importance of the organs debate it is imperative that the misunderstandings of it
      on which Benatar's criticisms are based are dispelled. Accordingly, I will
      consider and reject each of his objections in turn.

PMID- 15738443
TI  - Crisis in humanitarianism?

PMID- 15738444
TI  - Artificial gametes: new paths to parenthood?

PMID- 15738445
TI  - Summaries for patients. Development of type 2 diabetes among people participating
      in a program to promote healthy behaviors.

PMID- 15738446
TI  - Summaries for patients. The cost-effectiveness of strategies to prevent type 2
      diabetes.

PMID- 15738448
TI  - Summaries for patients. A low blood pressure target prevented kidney failure in
      patients with chronic kidney disease.

PMID- 15738447
TI  - Summaries for patients. Does hepatitis B vaccination protection continue after 15
      years?

PMID- 15738449
TI  - Summaries for patients. Ultrasonography to diagnose giant-cell arteritis.

PMID- 15738450
TI  - Incidence of type 2 diabetes in the randomized multiple risk factor intervention
      trial.
AB  - BACKGROUND: Weight loss and increased physical exercise reduce the risk for
      diabetes in people with impaired glucose tolerance. Randomized trial evidence on
      the effect of these interventions on people without impaired glucose tolerance is
      lacking. OBJECTIVE: To examine the influence of a comprehensive intervention
      program on the risk for developing diabetes in men without impaired glucose
      tolerance and in a post hoc subgroup analysis by baseline cigarette smoking
      status. DESIGN: Randomized, controlled trial. SETTING: 22 clinical centers for
      the Multiple Risk Factor Intervention Trial (MRFIT). PARTICIPANTS: 12,866 men age
      35 to 57 years at risk for cardiovascular disease were randomly assigned to
      either a special intervention or usual care group and followed for 6 to 7 years;
      this report focuses on 11,827 men without diabetes or impaired glucose tolerance
      at entry for whom follow-up glucose measurements were available. MEASUREMENTS:
      Cardiovascular disease risk factors, fasting blood glucose levels, and diabetes
      medication history were assessed before randomization and annually. INTERVENTION:
      Men in the special intervention group were counseled to change diet (reduce
      saturated fat, cholesterol, and calorie intake), to stop smoking, and to increase
      physical activity. Blood pressure was treated more intensively in the special
      intervention group than in the usual care group. RESULTS: 11.5% of the special
      intervention group and 10.8% of the usual care group developed diabetes over 6
      years of follow-up (hazard ratio, 1.08 [95% CI, 0.96 to 1.20]). The special
      intervention-usual care hazard ratio for diabetes was 1.26 (CI, 1.10 to 1.45)
      among smokers (63%) and 0.82 (CI, 0.68 to 0.98) among nonsmokers (37%). These
      estimates differed significantly (P = 0.0003). Weight gain after smoking
      cessation and the use of antihypertensive drugs may have counterbalanced the
      beneficial effect of the lifestyle intervention for the special intervention
      group smokers, while the lifestyle intervention was beneficial among nonsmokers.
      LIMITATIONS: Principal findings are based on a post hoc subgroup analysis.
      CONCLUSIONS: In nonsmokers, an intervention program that included nutrition
      counseling to produce reductions in weight, serum cholesterol, and (along with
      antihypertensive medication) blood pressure reduced the risk for diabetes.

PMID- 15738451
TI  - The cost-effectiveness of lifestyle modification or metformin in preventing type
      2 diabetes in adults with impaired glucose tolerance.
AB  - BACKGROUND: The Diabetes Prevention Program (DPP) demonstrated that interventions
      can delay or prevent the development of type 2 diabetes. OBJECTIVE: To estimate
      the lifetime cost-utility of the DPP interventions. DESIGN: Markov simulation
      model to estimate progression of disease, costs, and quality of life. DATA
      SOURCES: The DPP and published reports. TARGET POPULATION: Members of the DPP
      cohort 25 years of age or older with impaired glucose tolerance. TIME HORIZON:
      Lifetime. PERSPECTIVES: Health system and societal. INTERVENTIONS: Intensive
      lifestyle, metformin, and placebo interventions as implemented in the DPP.
      OUTCOME MEASURES: Cumulative incidence of diabetes, microvascular and neuropathic
      complications, cardiovascular complications, survival, direct medical and direct
      nonmedical costs, quality-adjusted life-years (QALYs), and cost per QALY. RESULTS
      OF BASE-CASE ANALYSIS: Compared with the placebo intervention, the lifestyle and
      metformin interventions were estimated to delay the development of type 2
      diabetes by 11 and 3 years, respectively, and to reduce the absolute incidence of
      diabetes by 20% and 8%, respectively. The cumulative incidence of microvascular,
      neuropathic, and cardiovascular complications were reduced and survival was
      improved by 0.5 and 0.2 years. Compared with the placebo intervention, the cost
      per QALY was approximately 1100 dollars for the lifestyle intervention and $31
      300 for the metformin intervention. From a societal perspective, the
      interventions cost approximately 8800 dollars and 29,900 dollars per QALY,
      respectively. From both perspectives, the lifestyle intervention dominated the
      metformin intervention. RESULTS OF SENSITIVITY ANALYSIS: Cost-effectiveness
      improved when the interventions were implemented as they might be in routine
      clinical practice. The lifestyle intervention was cost-effective in all age
      groups. The metformin intervention did not represent good use of resources for
      persons older than 65 years of age. LIMITATIONS: Simulation results depend on the
      accuracy of the underlying assumptions, including participant adherence.
      CONCLUSIONS: Health policy should promote diabetes prevention in high-risk
      individuals.

PMID- 15738452
TI  - Antibody levels and protection after hepatitis B vaccination: results of a 15
      year follow-up.
AB  - BACKGROUND: The duration of protection afforded by hepatitis B vaccination is
      unknown. OBJECTIVE: To determine antibody persistence and protection from
      hepatitis B virus (HBV) infection. DESIGN: Prospective cohort study. SETTING: 15
      villages in southwest Alaska. PARTICIPANTS: 1578 Alaska Natives vaccinated at age
      6 months or older. INTERVENTION: During 1981-1982, participants received 3 doses
      of plasma-derived hepatitis B vaccine. This cohort was followed annually over the
      first 11 years, and 841 (53%) persons were tested at 15 years. MEASUREMENTS:
      Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and
      testing to identify HBV variants. RESULTS: Levels of anti-HBs in the cohort
      decreased from a geometric mean concentration of 822 mIU/mL after vaccination to
      27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male
      sex were associated with persistence of higher anti-HBs levels at 15 years when
      analyzed by a longitudinal linear mixed model. After adjustment for initial anti
      HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest
      anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in
      16 participants and occurred more frequently in persons who did not respond to
      vaccination than those who responded (P = 0.01). Among infected persons with
      viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein
      variants, generally accompanied by wild-type HBV. LIMITATIONS: The loss of
      participants to follow-up at 15 years was 47%. However, characteristics of
      persons tested were similar to those of persons lost to follow-up. CONCLUSIONS:
      Hepatitis B vaccination strongly protected against infection for at least 15
      years in all age groups. Antibody levels decreased the most among persons
      immunized at 4 years of age or younger.

PMID- 15738453
TI  - The effect of a lower target blood pressure on the progression of kidney disease:
      long-term follow-up of the modification of diet in renal disease study.
AB  - BACKGROUND: Hypertension is a risk factor for progression of chronic kidney
      disease. The optimal blood pressure to slow progression is unknown. OBJECTIVE: To
      evaluate the effects of a low target blood pressure on kidney failure and all
      cause mortality. DESIGN: Long-term follow-up of the Modification of Diet in Renal
      Disease Study, a randomized, controlled trial conducted from 1989 to 1993.
      SETTING: 15 outpatient nephrology practices. PARTICIPANTS: 840 persons with
      predominantly nondiabetic kidney disease and a glomerular filtration rate of 13
      to 55 mL/min per 1.73 m2. INTERVENTION: A low target blood pressure (mean
      arterial pressure < 92 mm Hg) or a usual target blood pressure (mean arterial
      pressure < 107 mm Hg). MEASUREMENTS: After the randomized trial was completed,
      kidney failure (defined as initiation of dialysis or kidney transplantation) and
      a composite outcome of kidney failure or all-cause mortality were ascertained
      through 31 December 2000. RESULTS: Kidney failure occurred in 554 participants
      (66%), and the composite outcome occurred in 624 participants (74%). After Cox
      proportional hazards modeling and intention-to-treat analysis, the adjusted
      hazard ratios were 0.68 (95% CI, 0.57 to 0.82; P < 0.001) for kidney failure and
      0.77 (CI, 0.65 to 0.91; P = 0.0024) for the composite outcome in the low target
      blood pressure group compared with the usual target blood pressure group.
      Evidence was insufficient to conclude that the benefit of a low target blood
      pressure differed according to the cause of kidney disease, baseline glomerular
      filtration rate, or degree of proteinuria. LIMITATIONS: The exact mechanism
      underlying the benefit of a low target blood pressure is unknown. CONCLUSIONS:
      Assignment to a low target blood pressure slowed the progression of nondiabetic
      kidney disease in patients with a moderately to severely decreased glomerular
      filtration rate.

PMID- 15738454
TI  - Fumbled handoffs: one dropped ball after another.
AB  - Missed follow-up of abnormal test results and resultant delays in diagnosis is a
      safety issue that is gaining increasing attention. Despite increases in the
      numbers and types of available diagnostic tests, current systems in health care
      do not reliably ensure that test results are received and acted upon by ordering
      physicians. This article examines the case of a patient whose diagnosis of
      tuberculosis was substantially delayed because of systems problems, including
      poor continuity (with multiple-provider involvement), lack of communication of
      test results and other clinical information, and several handoffs. Strategies to
      ensure adequate communication of critical information and follow-up of test
      results are discussed, such as explicit criteria for communication of abnormal
      results, test-tracking systems for ordering providers, and use of information
      technologies.

PMID- 15738455
TI  - Meta-analysis: test performance of ultrasonography for giant-cell arteritis.
AB  - BACKGROUND: Giant-cell arteritis is a diagnostic challenge. PURPOSE: To determine
      the diagnostic performance of ultrasonography for giant-cell arteritis. DATA
      SOURCES: Studies published up to April 2004 in the MEDLINE, EMBASE, and Cochrane
      databases; reference lists; and direct contact with investigators. STUDY
      SELECTION: Studies in any language that examined temporal artery ultrasonography
      for diagnosis of giant-cell arteritis, enrolled at least 5 patients, and used
      biopsy or the American College of Rheumatology (ACR) criteria as the reference
      standard. DATA EXTRACTION: Two reviewers independently graded methodologic
      quality and abstracted data on sensitivity and specificity of ultrasonography for
      giant-cell arteritis. Diagnostic performance was determined for the halo sign,
      stenosis, or occlusion and for any of these ultrasonographic abnormalities. DATA
      SYNTHESIS: Weighted sensitivity and specificity estimates and summary receiver
      operating characteristic (ROC) curve analysis were used. Twenty-three studies,
      involving a total of 2036 patients, met the inclusion criteria. The weighted
      sensitivity and specificity of the halo sign were 69% (95% CI, 57% to 79%) and
      82% (CI, 75% to 87%), respectively, compared with biopsy and 55% (CI, 36% to 73%)
      and 94% (CI, 82% to 98%), respectively, compared with ACR criteria. Stenosis or
      occlusion was an almost equally sensitive marker compared with either biopsy
      (sensitivity, 68% [CI, 49% to 82%]) or ACR criteria (sensitivity, 66% [CI, 32% to
      89%]). Consideration of any vessel abnormality nonsignificantly improved
      diagnostic performance compared with ACR criteria. Between-study heterogeneity
      was significant, but summary ROC curves were consistent with weighted estimates.
      When the pretest probability of giant-cell arteritis is 10%, negative results on
      ultrasonography practically exclude the disease (post-test probability, 2% to 5%
      for various analyses). LIMITATIONS: The primary studies were small and of modest
      quality and had considerable heterogeneity. CONCLUSION: Ultrasonography may be
      helpful in diagnosing giant-cell arteritis, but cautious interpretation of the
      test results based on clinical presentation and pretest probability of the
      disease is imperative.

PMID- 15738456
TI  - Narrative review: aspirin resistance and its clinical implications.
AB  - Aspirin is currently the most cost-effective drug for the secondary prevention of
      cardiovascular disease, but treatment failures are relatively common. Several
      factors have been linked to these recurrent vascular events in patients
      prescribed aspirin, including smoking, drug interactions, nonadherence, comorbid
      conditions, and aspirin resistance. The term aspirin resistance has been used to
      describe not only an absence of the expected pharmacologic effects of aspirin on
      platelets but also poor clinical outcomes, such as recurrent vascular events, in
      patients treated with aspirin. Aspirin resistance is perhaps more precisely
      understood as the phenomenon of measurable, persisting platelet activation that
      occurs in patients prescribed a therapeutic dose of aspirin and may underlie an
      unknown proportion of aspirin treatment failures. Key challenges for future
      research are to standardize a definition of aspirin resistance and to compare
      whether different measures of platelet activation, either alone or in
      combination, independently predict cardiovascular events. These challenges must
      be met before researchers conduct studies to assess the clinical utility of
      testing on patient outcomes and cost-effective prescribing.

PMID- 15738457
TI  - Primary prevention of type 2 diabetes: lifestyle intervention works and saves
      money, but what should be done with smokers?

PMID- 15738458
TI  - Long-term protection of hepatitis B vaccine: lessons from Alaskan experience
      after 15 years.

PMID- 15738460
TI  - Care management for heart failure.

PMID- 15738459
TI  - Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in
      chronic heart failure.

PMID- 15738461
TI  - Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in
      chronic heart failure.

PMID- 15738462
TI  - Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in
      chronic heart failure.

PMID- 15738463
TI  - Demarcated truncal jaundice: a sign of retroperitoneal bile leakage.

PMID- 15738464
TI  - The international campaign to revitalise academic medicine.

PMID- 15738465
TI  - Molecular dynamics study of the lung surfactant peptide SP-B1-25 with DPPC
      monolayers: insights into interactions and peptide position and orientation.
AB  - We have performed molecular dynamics simulations of the interactions of the
      peptide SP-B(1-25), which is a truncated version of the full pulmonary surfactant
      protein SP-B, with dipalmitoylphosphatidylcholine monolayers, which are the major
      lipid components of lung surfactant. Simulations of durations of 10-20 ns show
      that persistent hydrogen bonds form between the donor atoms of the protein and
      the acceptors of the lipid headgroup and that these bonds determine the position,
      orientation, and secondary structure of the peptide in the membrane environment.
      From an ensemble of initial conditions, the most probable equilibrium orientation
      of the alpha-helix of the peptide is predicted to be parallel to the interface,
      matching recent experimental results on model lipid mixtures. Simulations of a
      few mutated analogs of SP-B(1-25) also suggest that the charged amino acids are
      important in determining the position of the peptide in the interface. The first
      eight amino acids of the peptide, also known as the insertion sequence, are found
      to be essential in reducing the fluctuations and anchoring the peptide in the
      lipid/water interface.

PMID- 15738466
TI  - Simulation studies of protein-induced bilayer deformations, and lipid-induced
      protein tilting, on a mesoscopic model for lipid bilayers with embedded proteins.
AB  - Biological membranes are complex and highly cooperative structures. To relate
      biomembrane structure to their biological function it is often necessary to
      consider simpler systems. Lipid bilayers composed of one or two lipid species,
      and with embedded proteins, provide a model system for biological membranes. Here
      we present a mesoscopic model for lipid bilayers with embedded proteins, which we
      have studied with the help of the dissipative particle dynamics simulation
      technique. Because hydrophobic matching is believed to be one of the main
      physical mechanisms regulating lipid-protein interactions in membranes, we
      considered proteins of different hydrophobic length (as well as different sizes).
      We studied the cooperative behavior of the lipid-protein system at mesoscopic
      time- and lengthscales. In particular, we correlated in a systematic way the
      protein-induced bilayer perturbation, and the lipid-induced protein tilt, with
      the hydrophobic mismatch (positive and negative) between the protein hydrophobic
      length and the pure lipid bilayer hydrophobic thickness. The protein-induced
      bilayer perturbation was quantified in terms of a coherence length, xi(P), of the
      lipid bilayer hydrophobic thickness profile around the protein. The dependence on
      temperature of xi(P), and the protein tilt-angle, were studied above the main
      transition temperature of the pure system, i.e., in the fluid phase. We found
      that xi(P) depends on mismatch, i.e., the higher the mismatch is, the longer
      xi(P) becomes, at least for positive values of mismatch; a dependence on the
      protein size appears as well. In the case of large model proteins experiencing
      extreme mismatch conditions, in the region next to the so-called lipid annulus,
      there appears an undershooting (or overshooting) region where the bilayer
      hydrophobic thickness is locally lower (or higher) than in the unperturbed
      bilayer, depending on whether the protein hydrophobic length is longer (or
      shorter) than the pure lipid bilayer hydrophobic thickness. Proteins may tilt
      when embedded in a too-thin bilayer. Our simulation data suggest that, when the
      embedded protein has a small size, the main mechanism to compensate for a large
      hydrophobic mismatch is the tilt, whereas large proteins react to negative
      mismatch by causing an increase of the hydrophobic thickness of the nearby
      bilayer. Furthermore, for the case of small, peptidelike proteins, we found the
      same type of functional dependence of the protein tilt-angle on mismatch, as was
      recently detected by fluorescence spectroscopy measurements.

PMID- 15738467
TI  - Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and
      Mg2+.
AB  - Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates affect
      cardiac excitability and contractility. To investigate how modulation by Mg(2+),
      ATP, and ADP of K(ATP) and L-type Ca(2+) channels influences excitation
      contraction coupling, we incorporated equations for intracellular ATP and MgADP
      regulation of the K(ATP) current and MgATP regulation of the L-type Ca(2+)
      current in an ionic-metabolic model of the canine ventricular myocyte. The new
      model: 1), quantitatively reproduces a dose-response relationship for the effects
      of changes in ATP on K(ATP) current, 2), simulates effects of ADP in modulating
      ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+) current
      during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio
      with normal total Mg(2+) or increased free Mg(2+) with normal ATP and ADP
      activate K(ATP) current, shorten action potential, and alter ionic currents and
      intracellular Ca(2+) signals. The model predictions are in agreement with
      experimental data measured under normal and a variety of pathological conditions.

PMID- 15738468
TI  - Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis.
AB  - The diagnosis of fetal alcohol spectrum disorder (FASD) is complex and guidelines
      are warranted. A subcommittee of the Public Health Agency of Canada's National
      Advisory Committee on Fetal Alcohol Spectrum Disorder reviewed, analysed and
      integrated current approaches to diagnosis to reach agreement on a standard in
      Canada. The purpose of this paper is to review and clarify the use of current
      diagnostic systems and make recommendations on their application for diagnosis of
      FASD-related disabilities in people of all ages. The guidelines are based on
      widespread consultation of expert practitioners and partners in the field. The
      guidelines have been organized into 7 categories: screening and referral; the
      physical examination and differential diagnosis; the neurobehavioural assessment;
      and treatment and follow-up; maternal alcohol history in pregnancy; diagnostic
      criteria for fetal alcohol syndrome (FAS), partial FAS and alcohol-related
      neurodevelopmental disorder; and harmonization of Institute of Medicine and 4
      Digit Diagnostic Code approaches. The diagnosis requires a comprehensive history
      and physical and neurobehavioural assessments; a multidisciplinary approach is
      necessary. These are the first Canadian guidelines for the diagnosis of FAS and
      its related disabilities, developed by broad-based consultation among experts in
      diagnosis.

PMID- 15738469
TI  - HIV, harm reduction and human rights.

PMID- 15738471
TI  - NNT for studies with long-term follow-up.

PMID- 15738472
TI  - How to diagnose diabetes.

PMID- 15738473
TI  - How to diagnose diabetes.

PMID- 15738474
TI  - Clinical trial budgets.

PMID- 15738475
TI  - Is topical treatment of osteoarthritis site-specific?

PMID- 15738477
TI  - Providing open access to research, one article at a time.

PMID- 15738478
TI  - Wanted: housing for 900,000 Sri Lankans.

PMID- 15738479
TI  - Quebec puts up 20 million dollars for C. difficile fight.

PMID- 15738480
TI  - Physician loses appeal of "zero tolerance" rule.

PMID- 15738481
TI  - Canadian company to develop mock pandemic vaccine.

PMID- 15738482
TI  - Administering antihypertensive drugs after acute ischemic stroke: timing is
      everything.

PMID- 15738483
TI  - Alzheimer's disease: genetic variables and risk.

PMID- 15738484
TI  - Identifying fetal alcohol spectrum disorder in primary care.

PMID- 15738485
TI  - Using a family history tool to prevent chronic diseases.

PMID- 15738486
TI  - An 89-year-old woman with cranial nerve dysfunction: diagnosis by observation.

PMID- 15738487
TI  - Should subclinical hypothyroidism in elderly patients be treated?

PMID- 15738488
TI  - Characteristics of women undergoing repeat induced abortion.
AB  - BACKGROUND: Although repeat induced abortion is common, data concerning
      characteristics of women undergoing this procedure are lacking. We conducted this
      study to identify the characteristics, including history of physical abuse by a
      male partner and history of sexual abuse, of women who present for repeat induced
      abortion. METHODS: We surveyed a consecutive series of women presenting for
      initial or repeat pregnancy termination to a regional provider of abortion
      services for a wide geographic area in southwestern Ontario between August 1998
      and May 1999. Self-reported demographic characteristics, attitudes and practices
      regarding contraception, history of relationship violence, history of sexual
      abuse or coercion, and related variables were assessed as potential correlates of
      repeat induced abortion. We used chi2 tests for linear trend to examine
      characteristics of women undergoing a first, second, or third or subsequent
      abortion. We analyzed significant correlates of repeat abortion using stepwise
      multivariate multinomial logistic regression to identify factors uniquely
      associated with repeat abortion. RESULTS: Of the 1221 women approached, 1145
      (93.8%) consented to participate. Data regarding first versus repeat abortion
      were available for 1127 women. A total of 68.2%, 23.1% and 8.7% of the women were
      seeking a first, second, or third or subsequent abortion respectively. Adjusted
      odds ratios for undergoing repeat versus a first abortion increased significantly
      with increased age (second abortion: 1.08, 95% confidence interval [CI] 1.04
      1.09; third or subsequent abortion: 1.11, 95% CI 1.07-1.15), oral contraceptive
      use at the time of conception (second abortion: 2.17, 95% CI 1.52-3.09; third or
      subsequent abortion: 2.60, 95% CI 1.51-4.46), history of physical abuse by a male
      partner (second abortion: 2.04, 95% CI 1.39-3.01; third or subsequent abortion:
      2.78, 95% CI 1.62-4.79), history of sexual abuse or violence (second abortion:
      1.58, 95% CI 1.11-2.25; third or subsequent abortion: 2.53, 95% CI 1.50-4.28),
      history of sexually transmitted disease (second abortion: 1.50, 95% CI 0.98-2.29;
      third or subsequent abortion: 2.26, 95% CI 1.28-4.02) and being born outside
      Canada (second abortion: 1.83, 95% CI 1.19-2.79; third or subsequent abortion:
      1.75, 95% CI 0.90-3.41). INTERPRETATION: Among other factors, a history of
      physical or sexual abuse was associated with repeat induced abortion.
      Presentation for repeat abortion may be an important indication to screen for a
      current or past history of relationship violence and sexual abuse.

PMID- 15738489
TI  - Staffing levels in not-for-profit and for-profit long-term care facilities: does
      type of ownership matter?
AB  - BACKGROUND: Currently there is a lot of debate about the advantages and
      disadvantages of for-profit health care delivery. We examined staffing ratios for
      direct-care and support staff in publicly funded not-for-profit and for-profit
      nursing homes in British Columbia. METHODS: We obtained staffing data for 167
      long-term care facilities and linked these to the type of facility and ownership
      of the facility. All staff were members of the same bargaining association and
      received identical wages in both not-for-profit and for-profit facilities.
      Similar public funding is provided to both types of facilities, although the
      amounts vary by the level of functional dependence of the residents. We compared
      the mean number of hours per resident-day provided by direct-care staff
      (registered nurses, licensed practical nurses and resident care aides) and
      support staff (housekeeping, dietary and laundry staff) in not-for-profit versus
      for-profit facilities, after adjusting for facility size (number of beds) and
      level of care. RESULTS: The nursing homes included in our study comprised 76% of
      all such facilities in the province. Of the 167 nursing homes examined, 109 (65%)
      were not-for-profit and 58 (35%) were for-profit; 24% of the for-profit homes
      were part of a chain, and the remaining homes were owned by a single operator.
      The mean number of hours per resident-day was higher in the not-for-profit
      facilities than in the for-profit facilities for both direct-care and support
      staff and for all facility levels of care. Compared with for-profit ownership,
      not-for-profit status was associated with an estimated 0.34 more hours per
      resident-day (95% confidence interval [CI] 0.18-0.49, p < 0.001) provided by
      direct-care staff and 0.23 more hours per resident-day (95% CI 0.15-0.30, p <
      0.001) provided by support staff. INTERPRETATION: Not-for-profit facility
      ownership is associated with higher staffing levels. This finding suggests that
      public money used to provide care to frail eldery people purchases significantly
      fewer direct-care and support staff hours per resident-day in for-profit long
      term care facilities than in not-for-profit facilities.

PMID- 15738490
TI  - Violence and abortions: what's a doctor to do?

PMID- 15738491
TI  - Reason and rights in global drug control policy.

PMID- 15738492
TI  - Antibiotic treatment for acute otitis media: time to think again.

PMID- 15738493
TI  - Tips for learners of evidence-based medicine: 4. Assessing heterogeneity of
      primary studies in systematic reviews and whether to combine their results.

PMID- 15738494
TI  - NICE, but will they help people with depression? The new National Institute for
      Clinical Excellence depression guidelines.

PMID- 15738495
TI  - Current strategies for investigating the genetic and environmental risk factors
      for affective disorders.

PMID- 15738496
TI  - "Psychiatric comorbidity": an artefact of current diagnostic systems?

PMID- 15738497
TI  - Randomised controlled trials relevant to aggressive and violent people, 1955
      2000: a survey.
AB  - BACKGROUND: Randomised trials remain the gold standard for evaluating health
      interventions. This applies to the criminal justice system as well as to health.
      AIMS: To identify and survey randomised trials relevant to forensic mental health
      services. METHOD: We searched 29 electronic bibliographic databases and acquired
      randomised trials involving sex offenders, arsonists or people clearly and
      actively aggressive, or abusive of children or spouse. Two researchers reliably
      extracted data. RESULTS: Of 409 studies found, we able to acquire 300 for further
      inspection. They all involved particularly violent people (total n=28 669),
      mostly adult men; the mean study size was 197 (median 52, mode 60, range 1
      1200).In these randomised trials over 700 interventions were evaluated and short
      term outcomes were recorded on 345 different scales. CONCLUSIONS: Wider
      collaboration, rationalising treatments and simplifying outcomes could further
      strengthen the tradition of trialling in forensic psychiatry. Systematic reviews
      of these studies are overdue.

PMID- 15738498
TI  - Personality and comorbidity of common psychiatric disorders.
AB  - BACKGROUND: We know little about the degree to which comorbidity, socommonly seen
      among psychiatric disorders, arises from variation in normal personality. AIMS:
      To study the degree to which variation in normal personality accounts for the
      comorbidity of eight common psychiatric and substance use disorders. METHOD:
      Internalising disorders (major depression, generalised anxiety and panic
      disorders, phobias), externalising disorders (alcohol and drug dependence,
      antisocial personality and conduct disorders) and personality dimensions of
      neuroticism, extraversion and novelty seeking were assessed in 7588 participants
      from a population-based twin registry. The proportion of comorbidity explained by
      each personality dimension was calculated using structural equation modelling.
      RESULTS: Neuroticism accounted for the highest proportion of comorbidity within
      internalising disorders (20-45%) and between internalising and externalising
      disorders (19-88%). Variation in neuroticism and novelty seeking each accounted
      for a modest proportion (10-12% and 7-14%, respectively) of the comorbidity
      within externalising disorders. Extraversion contributed negligibly. CONCLUSIONS:
      High neuroticism appears to be a broad vulnerability factor for comorbid
      psychiatric disorders. Novelty seeking is modestly important for comorbid
      externalising disorders.

PMID- 15738499
TI  - Reduced hippocampal volumes and memory loss in patients with early- and late
      onset depression.
AB  - BACKGROUND: Hippocampal volume reduction has been reported inconsistently in
      people with major depression. AIMS: To evaluate the interrelationships between
      hippocampal volumes, memory and key clinical, vascular and genetic risk factors.
      METHOD: Totals of 66 people with depression and 20 control participants underwent
      magnetic resonance imaging and clinical assessment. Measures of depression
      severity, psychomotor retardation, verbal and visual memory and vascular and
      specific genetic risk factors were collected. RESULTS: Reduced hippocampal
      volumes occurred in older people with depression, those with both early-onset and
      late-onset disorders and those with the melancholic subtype. Reduced hippocampal
      volumes were associated with deficits in visual and verbal memory performance.
      CONCLUSIONS: Although reduced hippocampal volumes are most pronounced in late
      onset depression, older people with early-onset disorders also display volume
      changes and memory loss. No clear vascular or genetic risk factors explain these
      findings. Hippocampal volume changes may explain how depression emerges as a risk
      factor to dementia.

PMID- 15738500
TI  - Hypofrontality in men with first-episode psychosis.
AB  - BACKGROUND: Decreased metabolic activity in the prefrontal cortex during
      cognitive activation is a recurrent finding and a likely functional marker of
      schizophrenia. AIMS: To investigate the occurrence of hypofrontality in patients
      with first-episode psychosis, with or without evolution to schizophrenia. METHOD:
      We used fluorodeoxyglucose positron emission tomography during the performance of
      an attention task and magnetic resonance imaging to study the dorsolateral
      prefrontal region in 13 men with a first episode of psychosis. Data from patients
      who progressed to schizophrenia were compared with those of patients who did not
      meet criteria for this diagnosis after 2 years. RESULTS: Patients who developed
      schizophrenia demonstrated a significant hypofrontality in the dorsolateral
      prefrontal cortex in comparison with the non-schizophrenia and control groups.
      CONCLUSIONS: Our results suggest that hypofrontality could be a marker of
      schizophrenia at the time of the first psychotic episode, in agreement with
      neurodevelopmental theories of schizophrenia.

PMID- 15738501
TI  - Neural correlates of syntax production in schizophrenia.
AB  - BACKGROUND: The production of grammatically complex sentences is impaired in
      schizophrenia. It has been suggested that impaired syntax processing reflects a
      risk for the disorder. AIMS: To examine the neural correlates of syntax
      production in people with schizophrenia using functional magnetic resonance
      imaging (fMRI). METHOD: Six patients with schizophrenia and six healthy
      volunteers spoke about seven Rorschach inkblots for 3 min each while correlates
      of brain activation were measured with fMRI. Participants produced varying
      amounts of syntactically simple and complex sentences during each 3 min run. The
      number of simple and complex sentences was correlated separately with the BOLD
      contrast. RESULTS: In the comparison between the control group and the patient
      group, the number of complex sentences produced was correlated with activation in
      the posterior portion of the right middle temporal (Brodmann area 21) and left
      superior frontal (BA10) gyriin the control group but not in the patients.
      CONCLUSIONS: The absence of activation in the right posterior temporal and left
      superior frontal cortex in patients with schizophrenia might contribute to the
      articulation of grammatically more simple speech in people with this disorder.

PMID- 15738502
TI  - Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex
      interactions.
AB  - BACKGROUND: Smoking may have a beneficial effect on either schizophrenic symptoms
      or antipsychotic side-effects, but studies are hampered by the lack of control of
      confounding factors. AIMS: To explore the self-medication hypothesis in a large
      sample of stable out-patients with schizophrenia. METHOD: Symptoms, assessed with
      the Positive and Negative Syndrome Scale (PANSS), and number of hospitalisations
      were compared in 250 out-patients with DSM-IV schizophrenia classified into three
      categories: highly dependent smokers, mildly dependent smokers and non-smokers.
      Log-linear analysis was used to control for potential confounding and interacting
      variables. RESULTS: High PANSS total scores and positive symptoms were less
      frequent in mildly dependent smokers than in non-smokers or highly dependent
      smokers. The highly dependent smokers had the worst outcome. CONCLUSIONS: The
      data do not generally support the self-medication hypothesis but rather suggest a
      complex interaction between nicotine dependence and nicotine dependence and
      schizophrenic symptoms.

PMID- 15738503
TI  - Escitalopram in the treatment of social anxiety disorder: randomised, placebo
      controlled, flexible-dosage study.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors are effective in the
      treatment of social anxiety disorder and are currently regarded as the
      pharmacotherapy of choice. AIMS: To investigate the efficacy and tolerability of
      escitalopram in the treatment of generalised social anxiety disorder. METHOD:
      Patients with generalised social anxiety disorder were randomised to receive
      placebo (n=177) or 10-20 mg escitalopram (n=181) in a 12-week, double-blind
      trial. The primary outcome measure was the mean change from baseline to last
      assessment in the Liebowitz Social Anxiety Scale (LSAS) total score. RESULTS: The
      study showed a statistically superior therapeutic effect for escitalopram
      compared with placebo on the LSAS total score (P=0.005). There were significantly
      more responders to treatment for escitalopram than for placebo (54% v. 39%;
      P<0.01). The clinical relevance of these findings was supported by significant
      reduction in the work and social components of the Sheehan Disability Scale and
      by the good tolerability of escitalopram treatment. CONCLUSIONS: Escitalopram was
      efficacious and well tolerated in the treatment of generalised social anxiety
      disorder.

PMID- 15738504
TI  - Assessing adolescent personality pathology.
AB  - BACKGROUND: Personality pathology constitutes a major form of psychopathology in
      adolescents. AIMS: To examine the reliability and validity of a Q-sort instrument
      for assessing adolescent personality pathology designed for clinically
      experienced informants. METHOD: A sample of 294 randomly selected psychiatrists
      and psychologists each provided data on a current patient, aged 14-18 years.
      Clinicians completed several measures, including the Shedler-Westen Assessment
      Procedure for Adolescents (SWAP-200-A). RESULTS: Factor analysis identified II
      dimensions of adolescent personality: psychopathology/malignant narcissism,
      dysphoria/inhibition, psychological health, histrionic sexualisation, schizotypy,
      sexual conflict, emotional dysregulation, anxious obsessionality, peer rejection,
      delinquent behaviour and attentional dysregulation. These correlated in predicted
      ways with a range of criterion variables, including measures of adaptive
      functioning, Axis II pathology, the Five Factor Model and the Child Behavior
      Checklist. CONCLUSIONS: The SWAP-200-A shows promise as an instrument for
      assessing personality pathology in adolescents. Trait dimensions such as
      delinquent behaviour and emotional dysregulation may prove useful additions to a
      classification of personality.

PMID- 15738505
TI  - Suitability and utility of the CORE-OM and CORE-A for assessing severity of
      presenting problems in psychological therapy services based in primary and
      secondary care settings.
AB  - BACKGROUND: There is a need for reliable assessment tools that are suitable for
      the counselling and the psychological therapy services in primary and secondary
      care settings. AIMS: To test the suitability and utility of the Clinical Outcomes
      in Routine Evaluation-Outcome Measure (CORE-OM) and CORE-Assessment (CORE-A)
      assessment tools. METHOD: Service intake data were analysed from counselling and
      psychological therapy services in 32 primary care settings and 17 secondary care
      settings. RESULTS: Completion rates exceeded 98% in both of the settings sampled.
      Intake severity levels were similar but secondary care patients were more likely
      to score above the risk cut-off and the severe threshold and to have experienced
      their problems for a greater duration. CONCLUSIONS: The CORE-OM and CORE-A are
      suitable assessment tools that show small but logical differences between
      psychological therapy services in primary- and secondary-based care.

PMID- 15738506
TI  - Psychiatric advance directives: qualitative study of informed deliberations by
      mental health service users.
AB  - BACKGROUND: Established legal mandates and high expectations for psychiatric
      advance directives are not matched by empirical evidence documenting their actual
      implementation. AIMS: To explore the interests, concerns and planning activities
      of informed mental health service users contemplating such directives. METHOD:
      Standard qualitative research techniques were used: field observations,
      interviews, focus groups, archival research and key informant interviews; 33
      persons participated in the interviews and focus groups. Transcripts were coded
      and analysed for thematic content, and results were member-checked. RESULTS:
      Training set in motion labour-intensive projects: conceptualising how a
      psychiatric advance directive would work in one's life, mobilising resources,
      reviewing past experiences and assessing risks. Especially meaningful was the
      prospect of being treated as a responsible agent in future interactions with the
      mental health system. CONCLUSIONS: Advance directives are best thought of as
      complex planning tools for future psychiatric crisis management, rather than
      focal interventions to enhance compliance. Research is needed to explore the
      institutional response to this prospective decision-sharing initiative.

PMID- 15738507
TI  - Repeated self-poisoning: increasing severity of self-harm as a predictor of
      subsequent suicide.
AB  - BACKGROUND: Prediction of suicide risk is difficult in clinical practice. AIMS:
      To identify changes in clinical presentation predictive of suicide in patients
      treated for repeated episodes of self-poisoning. METHOD: A nested case-control
      study used the Hunter Area Toxicology Service database to identify exposure
      variables and the National Death Index to identify suicide. Cases were patients
      who had hospital treatment on more than one occasion between 15 January 1987 and
      31 December 2000. RESULTS: There were 31 cases, for which 93 controls were
      selected. Study variables associated with an increased risk of subsequent suicide
      were an increase in the number of drugs ingested (odds ratio 2.59, 95% CI 1.48
      4.51), an increase in the dose ingested (OR 1.33, 95% CI 1.01-1.76), an increase
      in coma score (OR 1.71, 95% CI 1.11-2.66), a decrease in Glasgow Coma Score (OR
      1.21, 95% CI 1.03-1.43) and an increase in drug or alcohol misuse (OR 2.33, 95%
      CI 1.06-5.10). CONCLUSIONS: Patients who have escalating severity of self
      poisoning episodes are at high risk of completed suicide.

PMID- 15738508
TI  - Risk of puerperal and non-puerperal recurrence of illness following bipolar
      affective puerperal (post-partum) psychosis.
AB  - The clinical value of information on the risk of future psychiatric illness in
      women who have experienced puerperal (post-partum) psychosis has been limited by
      inconsistencies in terminology and nosology. Here we report rates of subsequent
      puerperal and non-puerperal episodes, in a well characterised sample of women
      diagnosed with clearly defined bipolar affective puerperal psychosis (n=103). Out
      of 54 women having further children, 31(57%; 95% CI 44-69) experienced an
      additional puerperal psychotic episode, and 64 of 103 women (62%; 95% CI 52-71)
      experienced a non-puerperal affective episode during the follow-up period (mean
      duration 9 years). A history of bipolar episodes prior to the puerperal psychosis
      did not predict risk following subsequent pregnancies, but positive family
      history of mental illness predicted shorter time to non-puerperal relapse.

PMID- 15738509
TI  - Suicide by hanging: multicentre study based on coroners' records in England.
AB  - We studied 162 cases of hanging by suicide occurring in 24 coroners'
      jurisdictions in England within a 6-month period in 2001. Prison and psychiatric
      ward suicides accounted for only 6% of these. The most frequently used ligatures
      (ropes, belts and cable) and ligature points (beams, girders, lofts and trees)
      are commonly available in community settings, limiting opportunities for
      prevention. In only half the cases (52%) were victims fully suspended with both
      feet off the ground. Four per cent had also taken an overdose.

PMID- 15738510
TI  - Integration of psychiatric and physical health.

PMID- 15738511
TI  - Reduction in hospital readmission rates for hyperbilirubinemia is associated with
      use of transcutaneous bilirubin measurements.

PMID- 15738512
TI  - Has the time arrived to replace the quick prothrombin time test for monitoring
      oral anticoagulant therapy?

PMID- 15738513
TI  - Quality specifications for B-type natriuretic peptide assays.
AB  - BACKGROUND: The objective of this report is to improve the quality of
      immunochemical measurements of B-type natriuretic peptide (BNP) and its N
      terminal propeptide (NT-proBNP). The recommendations proposed are intended for
      use by manufacturers of commercial assays, by clinical laboratories using those
      assays, by clinical trial groups and research investigators, and by regulatory
      agencies, such as the United States Food and Drug Administration. METHODS: A
      group of cardiac biomarker experts reviewed and abstracted the scientific
      literature to provide recommendations pertaining to the quality specifications
      for BNP/NT-proBNP assays. RESULTS: The evidence-based recommendations encourage
      manufacturers to endorse and consistently follow the proposed recommendations;
      encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform
      information on assay design, preanalytical performance characteristics,
      analytical performance characteristics, and clinical performance; and encourage
      regulatory agencies to adopt a minimal and uniform set of criteria for
      manufacturers to provide when seeking clearance for new and/or improved assays.
      CONCLUSIONS: These recommendations address the use of BNP and NT-proBNP as
      cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.

PMID- 15738514
TI  - High-sensitivity C-reactive protein: a useful marker for cardiovascular disease
      risk prediction and the metabolic syndrome.

PMID- 15738515
TI  - Discordance analysis characteristics as a new method to compare the diagnostic
      accuracy of tests: example of complexed versus total prostate-specific antigen.
AB  - BACKGROUND: ROC curve analysis is used to compare the overall diagnostic accuracy
      of tests, but its application to subgroups selected by a concentration range of
      only one marker may show severe biases. We developed a new approach, which we
      have named discordance analysis characteristics (DAC). METHODS: The DAC method is
      based on a generalization of the McNemar test so that for a given pair of cutoff
      values only those patients are analyzed who are categorized differently by the
      two tests compared. The analyses are performed for all cutoff pairs that deliver
      identical sensitivities for both tests. We used data for total (tPSA) and
      complexed prostate-specific antigen (cPSA) from a recently published multicenter
      study to demonstrate the DAC method. RESULTS: The example shows that ROC analyses
      of subgroups can give contradictory results about the diagnostic accuracy of two
      markers, depending on the marker used for the selection of subgroups. The DAC
      method avoids artifacts attributable to questionable selection of subgroups and
      facilitates overall and local comparisons of the diagnostic accuracy of tests.
      The DAC results of the analyzed data set suggest that cPSA has higher diagnostic
      accuracy than does tPSA. CONCLUSIONS: The DAC method is a suitable tool for
      comparing the clinical usefulness of laboratory markers. The DAC method could be
      considered as an additional tool to ROC analysis and could replace comparative
      ROC analyses of diagnostic tests, especially within subgroups defined by only one
      of the markers.

PMID- 15738517
TI  - Circulatory corticotropin-releasing hormone mRNA concentrations are increased in
      women with preterm delivery but not in those who respond to tocolytic treatment.

PMID- 15738516
TI  - Association of transcutaneous bilirubin testing in hospital with decreased
      readmission rate for hyperbilirubinemia.
AB  - BACKGROUND: Newborns are being discharged from hospitals within 1-2 days of
      birth, before hyperbilirubinemia usually becomes clinically evident. We
      investigated the use of transcutaneous bilirubin (TcB) before discharge to
      determine whether it affects the use of laboratory bilirubin testing or decreases
      the number of neonates readmitted for hyperbilirubinemia within 7 days of initial
      discharge. METHODS: We retrospectively searched a clinical laboratory and
      hospital database to determine the number of births, newborn readmission rates
      for hyperbilirubinemia, length of stay, and the number of bilirubin measurements
      in the clinical laboratory ordered for all babies in the newborn unit at the
      University of Texas Medical Branch from August 2002 to March 2003 (before TcB
      testing) and from May 2003 to December 2003 (after TcB). RESULTS: Between August
      2002 and December 2003, 8974 newborns (both vaginal and cesarean births) were
      admitted to the newborn nursery. Babies who did not fit the diagnosis-related
      group criteria of "normal newborn" were removed, leaving 6933 babies who were
      included in the study. April was considered a transition month and was not
      included in the study, leaving 6603 newborns to be included. Of these, 446 (6.8%)
      required phototherapy for treatment of hyperbilirubinemia before initial
      discharge. For the 8 months before and 8 months after initiation of TcB testing,
      the number of laboratory bilirubin measurements ordered per newborn did not
      change, nor did the mean (SD) length of stay for normal newborns [2.15 (1.1) days
      vs 2.12 (1.1) days; P = 0.53], nor days of treatment with phototherapy before
      discharge [2.9 (1.3) days vs 2.9 (1.3) days; P = 0.67]. By contrast, the number
      of readmissions per 1000 newborns per month for clinically significant
      hyperbilirubinemia decreased significantly (Wilcoxon rank-sums two-sample test, P
      = 0.044), from 4.5 (2.4) to 1.8 (1.7) after TcB testing was initiated.
      CONCLUSION: Access to TcB testing is associated with a reduction in the hospital
      readmission rate for hyperbilirubinemia within 7 days of the initial discharge.

PMID- 15738518
TI  - Detection of loss of heterozygosity by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry-based analysis of single
      nucleotide polymorphisms.

PMID- 15738519
TI  - Establishing a reference interval for measurement of flux through the
      mitochondrial fatty acid oxidation pathway in cultured skin fibroblasts.

PMID- 15738520
TI  - Application of a modified real-time PCR technique for relative gene copy number
      quantification to the determination of the relationship between NKX3.1 loss and
      MYC gain in prostate cancer.

PMID- 15738521
TI  - Treatment of maternal blood samples with formaldehyde does not alter the
      proportion of circulatory fetal nucleic acids (DNA and mRNA) in maternal plasma.

PMID- 15738522
TI  - Lack of dramatic enrichment of fetal DNA in maternal plasma by formaldehyde
      treatment.

PMID- 15738523
TI  - Quantification of thiol-containing amino acids linked by disulfides to LDL.

PMID- 15738524
TI  - Significance of urinary tartaric acid.

PMID- 15738525
TI  - Aberrant thyroid testing results in a clinically euthyroid patient who had
      received a tumor vaccine.

PMID- 15738526
TI  - Genetic screening for hemochromatosis: a cautionary tale.

PMID- 15738527
TI  - Increased serum concentrations of intestinal alkaline phosphatase in peritoneal
      dialysis.

PMID- 15738528
TI  - Molar DNA in maternal serum in a case of 46,XY heterozygous complete hydatidiform
      mole coexisting with a 46,XX twin live fetus.

PMID- 15738529
TI  - Prostate cancer chemotherapy: emerging from the shadows.

PMID- 15738530
TI  - Progress in the management of bone metastases: one continent at a time?

PMID- 15738531
TI  - Effect of docetaxel in patients with hormone-dependent prostate-specific antigen
      progression after local therapy for prostate cancer.
AB  - PURPOSE: To evaluate docetaxel in the treatment of patients with early-stage
      prostate cancer with prostate-specific antigen (PSA) progression after local
      therapy without androgen ablation therapy. PATIENTS AND METHODS: Twenty-five
      patients with adenocarcinoma of the prostate with PSA progression despite local
      therapy were treated with 70 mg/m2 docetaxel every 21 days. Treatment was planned
      for eight cycles. Patients were followed up for effects on PSA, testosterone, and
      toxicity. RESULTS: Twenty-three of 25 patients completed at least one full cycle
      of therapy. Ten (43%) of 23 patients demonstrated a decrease in PSA by > or = 50%
      for at least 4 weeks. The nadir decrease in PSA occurred beyond 150 days of
      therapy in most patients. Therapy was well tolerated. Grade 4 neutropenia with
      fever occurred in only six cycles (4.5%). Two patients required 25% dose
      reductions, both occurring with cycle 6, secondary to increased transaminases in
      one patient, and grade 3 lacrimation in the other patient. Two patients were
      removed after the first cycle of therapy due to toxicity (deep venous thrombosis,
      chest palpitations). Mean testosterone levels were not reduced in 17 patients
      assessed before and during therapy (P = .12). CONCLUSION: This study demonstrated
      the activity of docetaxel alone, without androgen ablation, in patients with PSA
      progression after completion of local therapy. Treatment with docetaxel in this
      population with early disease progression was well tolerated, biochemically
      active, and was not androgen ablative. Accrual to national phase III studies in
      early disease is now critical and should be strongly encouraged to determine the
      ability of early chemotherapy to improve survival.

PMID- 15738532
TI  - Treatment of chronic lymphocytic leukemia: achieving minimal residual disease
      negative status as a goal.

PMID- 15738533
TI  - HER2 or not HER2: that is the question.

PMID- 15738534
TI  - Short-course versus split-course radiotherapy in metastatic spinal cord
      compression: results of a phase III, randomized, multicenter trial.
AB  - PURPOSE: Hypofractionated radiotherapy (RT) is often used in the treatment of
      metastatic spinal cord compression (MSCC). This randomized trial was planned to
      assess the clinical outcome and toxicity of two different hypofractionated RT
      regimens in MSCC. PATIENTS AND METHODS: Three hundred patients with MSCC were
      randomly assigned to a short-course RT (8 Gy x 2 days) or to a split-course RT (5
      Gy x 3; 3 Gy x 5). Only patients with a short life expectancy entered the
      protocol. Median follow-up was 33 months (range, 4 to 61 months). RESULTS: A
      total of 276 (92%) patients were assessable; 142 (51%) treated with the short
      course and 134 (49%) treated with the split-course RT regimen. There was no
      significant difference in response, duration of response, survival, or toxicity
      found between the two arms. When short- versus split-course regimens were
      compared, after RT 56% and 59% patients had back pain relief, 68% and 71% were
      able to walk, and 90% and 89% had good bladder function, respectively. Median
      survival was 4 months and median duration of improvement was 3.5 months for both
      arms. Toxicity was equally distributed between the two arms: grade 3 esophagitis
      or pharyngitis was registered in four patients (1.5%), grade 3 diarrhea occurred
      in four patients (1.5%), and grade 3 vomiting or nausea occurred in 10 patients
      (6%). Late toxicity was never recorded. CONCLUSION: Both hypofractionated RT
      schedules adopted were effective and had acceptable toxicity. However,
      considering the advantages of the short-course regimen in terms of patient
      convenience and machine time, it could become the RT regimen of choice in the
      clinical practice for MSCC patients.

PMID- 15738535
TI  - Significantly higher pathologic complete remission rate after neoadjuvant therapy
      with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a
      randomized trial in human epidermal growth factor receptor 2-positive operable
      breast cancer.
AB  - PURPOSE: The objective of this study was to determine whether the addition of
      trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic
      complete response (pCR) rate in patients with human epidermal growth factor
      receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients
      with HER2-positive disease with operable breast cancer were randomly assigned to
      either four cycles of paclitaxel followed by four cycles of fluorouracil,
      epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous
      weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20%
      improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to
      chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic
      factors were similar in the two groups. After 34 patients had completed therapy,
      the trial's Data Monitoring Committee stopped the trial because of superiority of
      trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n =
      16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The
      decision was based on the calculation that, if study continued to 164 patients,
      there was a 95% probability that trastuzumab plus chemotherapy would be superior.
      Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared
      with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of
      this approach is not established, although no clinical congestive heart failure
      was observed. A more than 10% decrease in the cardiac ejection fraction was
      observed in five and seven patients in the chemotherapy and trastuzumab plus
      chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these
      data indicate that adding trastuzumab to chemotherapy, as used in this trial,
      significantly increased pCR without clinical congestive heart failure.

PMID- 15738536
TI  - Zoledronic acid significantly reduces skeletal complications compared with
      placebo in Japanese women with bone metastases from breast cancer: a randomized,
      placebo-controlled trial.
AB  - PURPOSE: To investigate the efficacy and safety of zoledronic acid for the
      treatment of bone metastases from breast cancer. PATIENTS AND METHODS: Women with
      bone metastases (N = 228) were randomly assigned to receive 4 mg zoledronic acid
      (n = 114) or placebo (n = 114) via 15-minute infusions every 4 weeks for 1 year.
      The primary efficacy end point was the skeletal-related event (SRE) rate ratio
      between treatment groups. An SRE was defined as pathologic fracture, spinal cord
      compression, and radiation or surgery to bone. Secondary end points included
      percentage of patients with at least one SRE, time-to-first SRE, and Andersen
      Gill multiple-event analysis. RESULTS: The SRE rate ratio at 1 year (excluding
      HCM and adjusted for prior fracture) was 0.61 (permutation test; P = .027),
      indicating that zoledronic acid reduced the rate of SRE by 39% compared with
      placebo. The percentage of patients with at least one SRE (excluding HCM) was
      significantly reduced by 20% by zoledronic acid (29.8% v 49.6% for placebo; P =
      .003). Zoledronic acid significantly delayed time-to-first SRE (median not
      reached v 364 days; Cox regression; P = .007) and reduced the risk of SREs by 41%
      in multiple event analysis (risk ratio = 0.59; P = .019) compared with placebo.
      Zoledronic acid was well tolerated with a safety profile similar to placebo. No
      patient treated with zoledronic acid had grade 3 or 4 serum creatinine increase.
      CONCLUSION: Zoledronic acid significantly reduced skeletal complications compared
      with placebo across multiple end points in Japanese women with bone metastases
      from breast cancer.

PMID- 15738537
TI  - Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line
      metastatic colorectal cancer: results of a randomized phase II trial.
AB  - PURPOSE: Bevacizumab, a monoclonal antibody against vascular endothelial growth
      factor, increases survival when combined with irinotecan-based chemotherapy in
      first-line treatment of metastatic colorectal cancer (CRC). This randomized,
      phase II trial compared bevacizumab plus fluorouracil and leucovorin (FU/LV)
      versus placebo plus FU/LV as first-line therapy in patients considered nonoptimal
      candidates for first-line irinotecan. PATIENTS AND METHODS: Patients had
      metastatic CRC and one of the following characteristics: age > or = 65 years,
      Eastern Cooperative Oncology Group performance status 1 or 2, serum albumin < or
      = 3.5 g/dL, or prior abdominal/pelvic radiotherapy. Patients were randomly
      assigned to FU/LV/placebo (n = 105) or FU/LV/bevacizumab (n = 104). The primary
      end point was overall survival. Secondary end points were progression-free
      survival, response rate, response duration, and quality of life. Safety was also
      assessed. RESULTS: Median survival was 16.6 months for the FU/LV/bevacizumab
      group and 12.9 months for the FU/LV/placebo group (hazard ratio, 0.79; P = .16).
      Median progression-free survival was 9.2 months (FU/LV/bevacizumab) and 5.5
      months (FU/LV/placebo); hazard ratio was 0.50; P = .0002. Response rates were
      26.0% (FU/LV/bevacizumab) and 15.2% (FU/LV/placebo) (P = .055); duration of
      response was 9.2 months (FU/LV/bevacizumab) and 6.8 months (FU/LV/placebo);
      hazard ratio was 0.42; P = .088. Grade 3 hypertension was more common with
      bevacizumab treatment (16% v 3%) but was controlled with oral medication and did
      not cause study drug discontinuation. CONCLUSION: Addition of bevacizumab to
      FU/LV as first-line therapy in CRC patients who were not considered optimal
      candidates for first-line irinotecan treatment provided clinically significant
      patient benefit, including statistically significant improvement in progression
      free survival.

PMID- 15738538
TI  - Retrospective analysis of selective lymphadenectomy in apparent early-stage
      endometrial cancer.
AB  - PURPOSE: Selective lymphadenectomy is widely accepted in the management of
      endometrial cancer. Purported benefits are individualization of adjuvant therapy
      based on extent of disease and resection of occult metastases. Our goal was to
      assess effects of the extent of selective lymphadenectomy on outcomes in women
      with apparent stage I endometrial cancer at laparotomy. PATIENTS AND METHODS:
      Patients with endometrial cancer who received primary surgical treatment between
      1973 and 2002 were identified through an institutional tumor registry. Inclusion
      criteria were clinical stage I/IIA disease and procedure including hysterectomy
      and selective lymphadenectomy (pelvic or pelvic + aortic). Exclusion criteria
      included presurgical radiation, grossly positive lymph nodes, or extrauterine
      metastases at laparotomy. Recurrence and survival were analyzed using Kaplan
      Meier analysis and Cox proportional hazards model. RESULTS: Among 509 patients,
      the median number of lymph nodes removed was 15 (median pelvic, 11; median
      aortic, three). Pelvic and aortic node metastases were found in 24 (5%) of 509
      patients and 11 (3%) of 373 patients, respectively. Patients with poorly
      differentiated cancers having more than 11 pelvic nodes removed had improved
      overall survival (hazard ratio [HR], 0.25; P < .0001) and progression-free
      survival (HR, 0.26; P < .0001) compared with patients having poorly
      differentiated cancers with 11 or fewer nodes removed. Number of nodes removed
      was not predictive of survival among patients with cancers of grade 1 to 2.
      Performance of aortic selective lymphadenectomy was not associated with survival.
      Three (27%) of 11 patients with microscopic aortic nodal metastasis are alive
      without recurrence. CONCLUSION: These data add to the literature documenting the
      possible therapeutic benefit of selective lymphadenectomy in management of
      patients with apparent early-stage endometrial cancer.

PMID- 15738539
TI  - Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia
      after alemtuzumab therapy is associated with prolonged survival.
AB  - PURPOSE: To test whether eradication of minimal residual disease (MRD) in B-cell
      chronic lymphocytic leukemia (CLL) by alemtuzumab is associated with a
      prolongation of treatment-free and overall survival. PATIENTS AND METHODS: Ninety
      one previously treated patients with CLL (74 men and 17 women; median age, 58
      years [range, 32 to 75 years]; 44 were refractory to purine analogs) received a
      median of 9 weeks of alemtuzumab treatment between 1996 and 2003. Regular bone
      marrow assessments by MRD flow cytometry were performed with the aim of
      eradicating detectable MRD (< 1 CLL cell in 10(5) normal cells). RESULTS:
      Responses according to National Cancer Institute-sponsored working group response
      criteria were complete remission (CR) in 32 patients (36%), partial remission
      (PR) in 17 patients (19%), and no response (NR) in 42 patients (46%). Twenty-two
      (50%) of 44 purine analog-refractory patients responded to alemtuzumab.
      Detectable CLL was eradicated from the blood and marrow in 18 patients (20%).
      Median survival was significantly longer in MRD-negative patients compared with
      those achieving an MRD-positive CR, PR, or NR. Patients achieving an MRD-negative
      CR had a longer treatment-free survival than patients with MRD-positive CRs, PR,
      or NR: MRD-negative CRs, not reached; MRD-positive CRs, 20 months; PRs, 13
      months; NR, 6 months (P < .0001). Overall survival for the 18 patients with MRD
      negative remissions was 84% at 60 months. Eight (47%) of the MRD-negative
      patients converted to MRD positivity at a median of 28 months. CONCLUSION: MRD
      negative remission in CLL is achievable with alemtuzumab, leading to an improved
      overall and treatment-free survival.

PMID- 15738540
TI  - The metabolic syndrome and disturbances in hormone levels in long-term survivors
      of disseminated testicular cancer.
AB  - PURPOSE: The metabolic syndrome may be an important risk factor for
      cardiovascular disease in long-term survivors of testicular cancer (TC). We
      investigated the associations between hormone levels and the metabolic syndrome
      in these men. PATIENTS AND METHODS: We included TC patients cured by orchidectomy
      and cisplatin-based chemotherapy, stage I TC patients after orchidectomy only,
      and healthy men of comparable age. Presence of the metabolic syndrome was
      determined using guidelines from the National Cholesterol Education Program Adult
      Treatment Panel III. Thyroid-stimulating hormone, follicle-stimulating hormone
      (FSH), inhibin B, luteinizing hormone (LH), total testosterone, sex-hormone
      binding globulin, free testosterone, estradiol, dehydroepiandrosterone sulfate,
      and insulin-like growth factor 1 were determined in blood. Cortisol metabolite
      excretion was measured in urine. RESULTS: Eighty-six chemotherapy patients
      (median follow-up, 7 years) were compared with 44 stage I patients and 47
      controls. LH and FSH were higher, and inhibin B and total and free testosterone
      were lower in chemotherapy patients than controls. Adrenal and thyroid hormone
      production were unaffected. Chemotherapy patients with the metabolic syndrome (n
      = 22; 26%) had a higher body mass index (BMI) pretreatment, a larger BMI increase
      during follow-up, lower total testosterone, and higher urinary cortisol
      metabolite excretion than those patients without the metabolic syndrome. BMI and
      insulin were associated with the metabolic syndrome, while total testosterone and
      urinary cortisol metabolite excretion were associated with BMI. CONCLUSION: We
      found gonadal dysfunction, but normal adrenal and thyroid function. Through its
      association with BMI, testosterone may play a role in the development of the
      metabolic syndrome in long-term TC survivors.

PMID- 15738541
TI  - Mutations of the epidermal growth factor receptor gene predict prolonged survival
      after gefitinib treatment in patients with non-small-cell lung cancer with
      postoperative recurrence.
AB  - PURPOSE: To evaluate the relationship between mutations of the epidermal growth
      factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in
      patients with recurrent lung cancer after pulmonary resection. PATIENTS AND
      METHODS: We sequenced exons 18-21 of the EGFR gene using total RNA extracted from
      59 patients with lung cancer who were treated with gefitinib for recurrent lung
      cancer. Gefitinib effectiveness was evaluated by both imaging studies and change
      in serum carcinoembryonic antigen (CEA) levels. RESULTS: EGFR mutations were
      found in 33 patients (56%). Of these mutations, 17 were deletions around codons
      746-750 and 15 were point mutations (12 at codon 858, three at other codons), and
      one was an insertion. EGFR mutations were significantly more prevalent in
      females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor
      shrinkage and/or CEA decrease to less than half of the baseline level in 26
      patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect
      was not assessable in nine patients. Female, never-smoking patients with
      adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was
      effective in 24 of 29 patients with EGFR mutations, compared with two of 21
      patients without mutations (P < .0001). Of note, del746-750 might be superior to
      L858R mutations for prediction of gefitinib response. Patients with EGFR
      mutations survived for a longer period than those without the mutations after
      initiation of gefitinib treatment (P = .0053). CONCLUSION: EGFR mutations were a
      good predictor of clinical benefit of gefitinib in this setting.

PMID- 15738542
TI  - Multicenter randomized phase II study of two schedules of docetaxel,
      estramustine, and prednisone versus mitoxantrone plus prednisone in patients with
      metastatic hormone-refractory prostate cancer.
AB  - PURPOSE: Mitoxantrone-corticosteroid is currently the standard palliative
      treatment in hormone-refractory prostate cancer (HRPC) patients. Recent clinical
      trials documented the high activity of the docetaxel-estramustine combination. We
      conducted a randomized phase II study to evaluate prostate-specific antigen (PSA)
      response (primary end point) and safety of two docetaxel-estramustine-prednisone
      (DEP) regimens and mitoxantrone-prednisone (MP). PATIENTS AND METHODS: One
      hundred thirty metastatic HRPC patients were randomly assigned to receive
      docetaxel (70 mg/m2 on day 2 or 35 mg/m2 on days 2 and 9 of each 21-day cycle)
      and estramustine (280 mg p.o. tid on days 1 through 5 and 8 through 12) or
      mitoxantrone 12 mg/m2 every 3 weeks; all patients received prednisone (10 mg
      daily). RESULTS: One hundred twenty-seven patients were assessable for PSA
      response and safety. A > or = 50% PSA decline was found in a greater percentage
      of patients in the docetaxel arms (67% and 63%) compared with MP (18%; P =
      .0001). Median time to PSA progression was five times longer with DEP than with
      MP (8.8 and 9.3 v 1.7 months, respectively; P = .000001). Overall survival was
      better in the docetaxel arms (18.6 and 18.4 months) compared with the MP arm
      (13.4 months), but not significantly so (P = .3). Crossover rates differed
      significantly among treatment arms (16%, 10%, and 48% in arms A, B, and C,
      respectively; P = .00001). Treatment-related toxicities were mild and mainly
      hematologic. CONCLUSION: The results of this randomized phase II study showed
      significantly higher PSA decline < or = 50% and longer times to progression in
      HRPC patients receiving DEP-based chemotherapy than MP, and that DEP could be
      proposed in this setting.

PMID- 15738543
TI  - Hidden by HIPAA: the costs of cure.

PMID- 15738544
TI  - Lymphadenectomy in apparent early-stage endometrial carcinoma: do numbers count?

PMID- 15738545
TI  - Bevacizumab plus fluorouracil: the value of being part of a developing story.

PMID- 15738546
TI  - Radiation therapy alone for spinal cord compression: time to improve upon a
      relatively ineffective status quo.

PMID- 15738547
TI  - What is more exciting? The activity of docetaxel in early prostate cancer or the
      successful collaboration between urologists and medical oncologists to complete a
      study in early prostate cancer?

PMID- 15738548
TI  - Goodbye mercury? Blood pressure measurement and its future.

PMID- 15738549
TI  - Osler, Flexner, apprenticeship and 'the new medical education'.

PMID- 15738550
TI  - Community diabetes: an East London perspective.
AB  - The rising prevalence of type 2 diabetes in the UK has necessitated a change in
      the delivery of diabetes care, with a shift of focus from hospital to community.
      The National Service Framework for Diabetes has enshrined this approach, and the
      new General Medical Services (GMS2) contract rewards primary healthcare
      professionals for developing high-quality diabetes care. New approaches cross the
      primary/secondary care divide and are patient focused. The evolution of diabetes
      care in the UK is illustrated by service developments in Newham, East London.

PMID- 15738551
TI  - Recurrent abdominal pain in childhood.

PMID- 15738552
TI  - Emergency department airway management in the UK.

PMID- 15738553
TI  - Reliability of automated blood pressure devices used by hypertensive patients.
AB  - Automated blood pressure (BP) devices are used by many hypertensive patients in
      Hong Kong, with or without medical advice. At two community clinics, we invited
      hypertensive patients aged between 40 and 70 years who used such a device to fill
      in a questionnaire and to have four sets of BP measurements, automated and
      mercury, at two visits. Of 290 hypertensive patients 120 fulfilled the criteria,
      and 73 of these agreed to participate. 53 devices measured arm BP, 21 measured
      forearm BP. The agreement between the mercury sphygmomanometer and the automated
      devices was poor, with average differences of 9.5 mmHg for systolic and 9.4 mmHg
      for diastolic and no clear advantage for either site of measurement. As a means
      of screening for BP >140/90 mmHg the sensitivity of the automated devices was 81%
      and the specificity was 80%. There were large variations in how often and under
      what circumstances the devices had been used. One-fifth of the devices had been
      acquired on medical advice but only 11% of the participants were aware of the
      three important conditions for operating such devices. Discussion of automated
      devices, their role and proper use, should now be part of routine hypertensive
      care.

PMID- 15738554
TI  - Nicotinic antagonists in the treatment of nerve agent intoxication.

PMID- 15738555
TI  - A time capsule for patients with dementia?

PMID- 15738556
TI  - Good's syndrome with primary intrapulmonary thymoma.

PMID- 15738557
TI  - Spontaneous bilateral tubal ectopic pregnancy.

PMID- 15738558
TI  - Acute renal infarction.

PMID- 15738559
TI  - Painful attraction: a magnetic penile injury.

PMID- 15738560
TI  - Scabies in Edinburgh from 1815 to 2000.

PMID- 15738561
TI  - Human endogenous retroviruses in health and disease.

PMID- 15738562
TI  - Human endogenous retroviruses in health and disease.

PMID- 15738563
TI  - Conjoined twins, delivery and the memory of medicine.

PMID- 15738564
TI  - Brain imaging in fatigue syndromes.

PMID- 15738565
TI  - Myocardial infarction after aspirin.

PMID- 15738566
TI  - Access to scrotal ultrasonography.

PMID- 15738567
TI  - Sir Thomas Browne's birthday.

PMID- 15738568
TI  - Achilles tendinopathy.

PMID- 15738571
TI  - Sir Thomas Browne's birthday.

PMID- 15738572
TI  - Sir Thomas Browne's birthday.

PMID- 15738574
TI  - Use of magnetic resonance imaging in predicting further vascular events among
      patients with transient ischemic attacks.

PMID- 15738573
TI  - Circulating transforming growth factor-beta1 levels in asymptomatic carotid
      plaques.

PMID- 15738575
TI  - Informed consent for thrombolytic therapy in acute ischemic stroke.

PMID- 15738576
TI  - NINDS Stroke Trial data reanalysis leaves issues unresolved.

PMID- 15738577
TI  - Adverse effects of the intraluminal filament model of middle cerebral artery
      occlusion.

PMID- 15738578
TI  - Strategies in motor stroke rehabilitation.

PMID- 15738579
TI  - Glucose metabolism, noradrenaline release, and MK-801 in intracerebral
      hemorrhage.

PMID- 15738580
TI  - Cardiac myofibril formation is not affected by modification of both N- and C
      termini of sarcomeric tropomyosin.
AB  - Although the role of tropomyosin is well-defined in striated muscle, the precise
      mechanism of how tropomyosin functions is still unclear. It has been shown that
      extension of either N- or C-terminal ends of sarcomeric tropomyosin do not affect
      cardiac myofibrillogenesis, but it is not known whether simultaneous extension of
      both ends affects the process. For studying structural/functional relationships
      of sarcomeric tropomyosin, we have chosen the Ambystoma mexicanum because cardiac
      mutant hearts are deficient in sarcomeric tropomyosin. In this study, we have
      made an expression construct, pEGFP.TPM4alpha.E-L-FLAG, that, on transfection
      into normal and mutant axolotl hearts in organ culture, expresses GFP.TPM4alpha.E
      L-FLAG fusion protein in which both the N- and C-termini of TPM4alpha are being
      extended. TPM4alpha is one of the three tropomyosins expressed in normal axolotl
      hearts. Both confocal and electron microscopic analyses show that this modified
      sarcomeric tropomyosin can form organized myofibrils in axolotl hearts.

PMID- 15738581
TI  - Possible involvement of NADPH oxidase and JNK in homocysteine-induced oxidative
      stress and apoptosis in human umbilical vein endothelial cells.
AB  - Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases,
      although the mechanism leading to vascular dysfunction is not clear. The aim of
      this study was to examine the effect of homocysteine (Hcy) on oxi-dative stress
      and apoptosis in human umbilical vein endothelial cells (HUVECs). HUVECs were
      challenged for 24 h with Hcy (10 microM-3 mM) in the presence of various stress
      signaling inhibitors, including the nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase inhibitor apocynin (100 microM), the p38 mito-gen-activated
      protein kinase inhibitor SB203580 (2.5 microM), the extracellular signal
      regulated kinase inhibitor U0126 (2.5 microM), the stress-activated protein
      kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) inhibitor JNK inhibitor II (10
      microM), and antioxidants alpha-tocopherol (5 microg/mL) and N-acetyl cysteine
      (NAC, 2 mM). Reactive oxygen species (ROS) were detected using 5-(6)-chloromethyl
      2',7'-dichlorodihydrofluorescein diacetate. Apoptosis was evaluated by 4',6'
      diamidino-2'-phenylindoladihydrochloride staining, annexin-V phosphatidyl-
      serine/propidium iodide, and caspase-3 assay. NADPH oxidase and SAPK/JNK signal
      were evaluated with immunoblotting. Hcy significantly enhanced ROS generation and
      apoptosis after 24-h incubation. Apocynin prevented Hcy-induced ROS generation
      but only partially restored Hcy-induced apoptosis. JNK inhibitor II, alpha
      tocopherol, and NAC partially reduced Hcy-induced apoptosis, although SB203580
      and U0126 had no effect. Immunoblotting analysis confirmed upregulation of NADPH
      oxidase and SAPK/JNK signaling. Collectively, our results suggested that Hcy may
      induce oxidative stress and apopto-sis through an NADPH oxidase and/or JNK
      dependent mechanism(s).

PMID- 15738582
TI  - T-cell receptor vbeta8.1 peptide reduces coxsackievirus-induced cardiopathology
      in aged mice.
AB  - Viral myocarditis is an important cause of heart failure and cardiomyopathy.
      Immunosenescence, characterized by a dramatic reduction in immune responsiveness,
      can increase susceptibility to cardiopathology from viral infections. The T-cell
      receptor (TCR) Vbeta 8.1 peptide, a 16-mer peptide, has shown immuno-regulating
      and immunostimulating effects in viral-induced immunodeficiency. In our study, 18
      mo-old C57Bl/6 female mice were treated twice with TCR Vbeta8.1 peptide and 10 d
      before sacrifice were injected ip with coxsackievirus B3. Cardiac histopathology
      was assessed for lesion severity. Splenocyte cyto-kine production (interleukin-2,
      -4, -6, interferon-gamma) and heart viral titers were determined. Our data
      suggest that immunosenescence suppressed both T helper (Th1) and Th2 cytokine
      production and that treatment with TCR Vbeta8.1 peptide induced cytokine
      stimulation close to levels seen in young mice. Nontreated aged mice developed
      some degree of myocarditis (75% mild and 25% severe), whereas only 35% of the
      peptide-treated aged group developed cardiopathology, with 25% being mild and 10%
      severe. Heart tissue from nontreated aged mice infected with coxsackievirus had a
      higher viral titer than hearts of aged mice equally infected but treated with the
      peptide. In conclusion, TCR Vbeta8.1 peptide induced immunoregulation, and
      inhibited or reduced coxsackievirus B3-induced cardiopathology in aged mice.

PMID- 15738584
TI  - Increased mitral valve regurgitation and myocardial hypertrophy in two dogs with
      long-term pimobendan therapy.
AB  - The aim of this article is to describe original adverse effects in two dogs
      chronically treated with the inodilator pimobendan. We report a German shepherd
      (i.e., dog 1) and a poodle (i.e., dog 2) that were referred to our cardiology
      unit after receiving pimobendan for 10 and 5 mo, respectively. In both dogs,
      conventional echo-Doppler examination demonstrated mitral valve regurgitation and
      myocardial hypertrophy. Tissue Doppler imaging (TDI) was performed in the first
      case and revealed an abnormal relaxation phase. After the first examination,
      pimobendan administration was stopped in both cases and dogs were re-examined 3
      and 1 mo later, respectively. Mitral valve regurgitation assessed by
      echocardiography decreased in both dogs, and the systolic heart murmur
      disappeared in dog 1. Importantly, most echocardiographic and TDI parameters
      tended to normalize in dog 1, suggesting, at least partial reversal of both
      myocardial hypertrophy and relaxation abnormality produced during inodilator
      therapy. This is the first report to describe an increase in mitral regurgitation
      under clinical conditions in dogs treated with pimobendan. We also suggest that
      pimobendan may induce ventricular hypertrophy. However, prospective studies are
      needed to confirm this observation.

PMID- 15738583
TI  - Neovascularization and angiogenic gene expression following chronic arsenic
      exposure in mice.
AB  - Exposure to arsenic in drinking water increases incidence of cardiovascular
      diseases. However, the basic mechanisms and genetic changes that promote these
      diseases are unknown. This study investigated the effects of chronic arsenic
      exposure on vessel growth and expression of angiogenic and tissue remodeling
      genes in cardiac tissues. Male mice were exposed to low to moderately high levels
      of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in
      Matrigel implants was tested during the last 2 wk of each exposure period.
      Implant vascularization increased in mice exposed to 5-500 ppb AsIII for 5 wk.
      Similar increases were seen following exposure to 50-250 ppb of AsIII over 20 wk,
      but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA
      revealed differential expression of angiogenic or tissue remodeling genes, such
      as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen
      activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied
      with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel
      density were reduced by exposure to 500 ppb AsIII for 20 wk. These data
      demonstrate differential concentration and time-dependent effects of chronic
      arsenic exposure on cardiovascular phenotype and vascular remodeling that may
      explain the etiology for AsIII-induced disease.

PMID- 15738585
TI  - Effects of ambasilide in isolated perfused guinea pig heart: use dependence.
AB  - There has been increased interest in class III antiarrhythmic drugs for con
      version of atrial fibrillation to sinus rhythm. Ambasilide, a class III
      antiarrhythmic, has been shown to block multiple cardiac channels in a variety of
      animals including humans. Although the electrophysiological effects of ambasilide
      are characterized on the cellular level, its effects on an organ level have yet
      to be investigated. We investigated escalating doses of ambasilide in isolated,
      per-fused guinea pig hearts. Ambasilide prolonged the RR, PQ, QRS, QT, and QTc
      (F) in a concentration-dependent manner in either normal sinus rhythm or with
      reduced heart rate (atriectomy). dP/dtmin was increased (became less negative) in
      the presence of increasing concentrations of ambasilide, whereas the vehicle
      produced less negative lusitropy. Ambasilide demonstrated use dependence by
      prolonging QTc (F) less at slower heart rates. Ambasilide also inhibited
      isoproterenol-induced tachycardia, suggesting it exerts beta-adrenergic blocking
      properties. In conclusion, this study suggests that ambasilide has multichannel
      blocking properties including beta-adrenergic antagonism.

PMID- 15738586
TI  - Bile acids are toxic for isolated cardiac mitochondria: a possible cause for
      hepatic-derived cardiomyopathies?
AB  - Cholestasis and other liver diseases may affect the heart through the toxic
      effects of the retained bile acids on cardiac mitochondria, which could explain
      the origin of hepatic-derived cardiomyopathies. The objective of this work was to
      test the hypothesis that bile acids are toxic to heart mitochondria for
      concentrations that are relevant for cholestasis. Heart mitochondria were
      isolated from rat and subjected to incubation with selected bile acids
      (litocholic acid [LCA], deoxycholic acid [DCA], chenodeoxycholic acid [CDCA],
      glycochenodeoxycholic acid [GCDC], taurodeoxycholic acid [TDCA], and
      glycoursodeoxycholic acid [GUDC]). We observed that the most toxic bile acids
      were also the most lipophilic ones (LCA, DCA, and CDCA), inducing a decrease on
      state 3 respiration, respiratory control ratio, and membrane potential and
      causing the induction of the mitochondrial permeability transition. GUDC was the
      bile acid with lower indexes of toxicity on isolated heart mitochondria. The
      results of this research indicate that at toxicologically relevant
      concentrations, most bile acids (mainly the most lipophilic) alter mitochondrial
      bioenergetics. The impairment of cardiac mitochondrial function may be an
      important cause for the observed cardiac alterations during cholestasis.

PMID- 15738587
TI  - Diminished myofibril organization in mutant axolotl hearts transfected with site
      directed mutants of sarcomeric tropomyosins.
AB  - We used a model lacking endogenous sarcomeric tropomyosin, the cardiac mutant of
      the Mexican axolotl, to examine the effect of mutant tropomyosins on sarcomeric
      myofibril formation. Previous studies have introduced wild-type mouse alpha
      tropomyosin into mutant hearts in organ culture with subsequent for-mation of
      organized myofibrils. This study examines the predominant embry-onic axolotl TPM
      4 type tropomyosin (TPM4alpha), containing a conservative re- placement of
      glutamic acid for aspartic acid at the clinically important 175 site. In this
      study, ATmC-3 (TPM4alpha) promoted formation of organized myofibrils in hearts
      without endogenous tropomyosin. Site-directed mutagenesis of 175 glutamic acid
      with 175 glutamine or 175 lysine was toxic to the formation of organized
      myofibrils in mutant hearts in the absence of endogenous tropo-myosin. Cationic
      liposome co-transfection of both wild-type tropomyosin and Glu175Gln.TPM4alpha
      cDNA formed organized myofibrils in mutant hearts. A construct with
      GFP.Glu175Gln.TPM4alpha cDNA was used to confirm expression of the mutant fusion
      protein. Mutation at the 175 site in TPM4alpha type or TPM1alpha (striated muscle
      isoform of the TPM1 gene) was sufficient to alter the protein such that organized
      myofibrils would not form in ventricles of mutant hearts without endogenous
      tropomyosin.

PMID- 15738588
TI  - [Malignant vascular tumours in children -- report from the Polish Pediatric Rare
      Tumors Study].
AB  - Malignant vascular tumours represent a rare group of neoplasms, usually treated
      according to protocols for soft tissue sarcomas. THE AIM OF THE STUDY: To assess
      the clinical characteristics, disease course and outcome in Polish children with
      malignant vascular neoplasms. MATERIAL AND METHODS: The Polish Paediatric Rare
      Tumours Study retrospectively analysed multicentre data on 32 children with
      vascular tumours, registered between 1992 and 2002. On the basis of the
      histological type of the neoplasm these patients have been divided into three
      groups: group I -- 10 patients with angiosarcoma (ASA), group II -- 7 children
      with haemangioendothelioma (HE) and group III- 15 patients with
      haemangiopericytoma (HP), of both infantile (7 children) and adult-types (8
      patients). RESULTS: Group I: 5 patients presented with local, 3 with systemic and
      2 with regional disease. Primary complete resection (PRC) was performed in 7
      patients, not resulting in local control in any of them. Radiotherapy (RTX) was
      administered in 5 patients, chemotherapy (CHT) in all. 7 patients relapsed, 3
      never entered clinical remission. 9 of the 10 patients of group I, died of
      disease progression. Group II: PRC was performed in 5 patients and led to local
      control in 2. Adjuvant RTX was used in 2 and CHT in 4 patients. 2 children
      relapsed and died of the disease. Infantile HP: PRC was performed in 3 children,
      remaining 4 patients received adjuvant CHT All children entered complete
      remission and are disease-free. Adult-type HP: PRC was performed in 5 patients,
      resulting in local control in 4. Five children were given adjuvant RTX and six
      CHT Three patients relapsed and died of disease progression. CONCLUSIONS: The
      effectiveness of primary complete resection in all groups was doubtful. The high
      rate of metastatic relapses suggests that the currently given systemic therapy is
      not satisfactory. The only tumour with excellent prognosis was infantile type HP
      (all patients are alive and free of disease). Adequate treatment for children
      with angiosarcoma remains still unknown -- 9 of 10 patients died of disease
      progression. Prognosis in patients with haemangioendothelioma is intermediate,
      however the role of immunotherapy should be further investigated.

PMID- 15738590
TI  - Characteristics and outcome of children with primary soft tissue sarcomas of
      extremities.
AB  - OBJECTIVES: To determine the characteristics and outcome or patients with primary
      soft tissue sarcomas of extremities in children. MATERIAL AND METHODS: Thirty-six
      patients treated for soft tissues sarcomas were enrolled into the study. Features
      analysed: the incidence of soft tissues sarcoma of extremities, the time from
      first clinical symptoms to making the diagnosis, the primary site of tumour;
      histopathologic type of tumour, stage of disease, methods and results of the
      treatment. RESULTS: The time From first symptoms to making the diagnosis was 5.4
      months (mean). The site of the tumour was the femur in 6 patients, arm in 3, knee
      in 1. Histopathologic types: synovial sarcoma in 4 patients, malignant
      haemangiopericytoma in 2, rhabdomyosarcoma in 2, sarcoma myogenes in 1, primitive
      neuroectodermal tumour in l. Stage of disease: III deg. -- 8 patients, IV deg. --
      2. Patients underwent treatment according to the soft tissue sarcoma protocols.
      Results of treatment: first complete remission was observed in 7 patients; second
      complete remission in 1, one patient is on postoperative treatment. One patient
      died. CONCLUSIONS: 1. Combined treatment achieves full remission in the majority
      of patients with soft tissues sarcomas localized within the limbs. 2. In patients
      with large tumours (>5 cm) the treatment should to be started with inductive
      chemotherapy, and the surgery should be postponed. 3. Early excision of the
      tumour should be considered in cases of small tumours (< 5 cm), when resection
      with wide margin of healthy tissues is possible, without deteriorating the
      function of the limb or cosmetic damage.

PMID- 15738589
TI  - [Malignant pelvic neoplasms in children treated in two Polish oncology centres].
AB  - BACKGROUND: Extensive diagnostic and therapeutic dilemmas appear in children With
      primary malignant neoplasms located in the minor pelvis. THE AIM OF THE STUDY: To
      evaluate the clinical symptoms, disease course and the results of treatment in
      patients with malignant pelvic neoplasms. MATERIAL AND METHODS: The study
      included 31 children (13 boys and 18 girls; aged 2 months to 16 years; mean age -
      8 years) treated in the Departments of Paediatric Oncology and Haematology in
      Gdansk and Lublin during the period of 1992-2003. The group comprised 17 patients
      with soft tissue sarcomas (MTM) (55%), 12 with germinal tumours (TGM) (39%) and
      tow. with neuroblastoma (NBL) (6%). The great majority of children (90%)
      presented with highly advanced disease (stages III + IV -- in 28 out of 31
      patients). RESULTS: with data analysis we were able to distinguish two categories
      of patients with different prognosis: with MTM and TGM. Most of he MTM tumours
      (11/17 - 65%) were localized in the urinary tract, the remaining six developed
      within pelvic muscles. Ten out of twelve TGM tumours (83%) were located in the
      ovaries. Radical tumour resection, especially primary resection, was shown to
      play the key role in both groups. Among TGM patients it was performed in 75%
      while in MTM patients -- in only 12%. All of these patients entered clinical
      remission and remain disease free. After adjuvant chemo- and/or radiotherapy
      secondary tumour resection was done in 17% of TGM and 41% of MTM patients.
      CONCLUSION: in patients, who were not able to undergo radical tumour resection
      (mainly MTM patients), the disease progressed and led to death.

PMID- 15738591
TI  - [Central nervous system metastases in children with solid tumours].
AB  - BACKGROUND: Central nervous system (CNS) metastases occur in 20-30% of adult
      patients with systemic cancers. but they rarely occur in children with solid
      tumours. AIM: clinical and prognostic characteristics of CNS recurrence in
      children treated for solid tumours were analysed. PATIENTS AND METHODS: The
      retrospective study enrolled 218 children treated for solid tumours in the
      Department of Paediatric Haematology and Oncology, Lublin Medical Academy, from
      January 1992 to December 2002. The diagnosis in this group was as follow: soft
      tissue sarcomas -- 51 patients, bone tumours -- 50. Wilms' tumour -- 48,
      neuroblastoma (NBL) -- 36, germ cell tumours -- 33: Children with primary CNS
      tumours, retinoblastoma, lymphoma and rare tumours were not analysed. RESULTS:
      CNS metastases were diagnosed in five children (2.3%) - (2 boys. 3 girls; aged
      2,5 to 17 years). Two of them were treated due to Wilms' tumour, one -- NBL, one 
      - teratoma malignum, one -- leiomyosarcoma. None of the children with bone
      tumours had CNS metastases. Diagnosis of CNS metastases was confirmed by imaging
      studies (CT, MRI). The median time from initial diagnosis to the detection of CNS
      metastases was 14 months. Two children underwent surgical resection of solitary
      metastases. One of them was also irradiated and received chemotherapy and only
      this child is alive and achieved complete remission. Other children died, with
      median period of 32 days. CONCLUSIONS: CNS metastases may occur in children with
      the recurrence of primary neoplastic disease. The prognosis is grave.

PMID- 15738592
TI  - [Solid tumours of the vertebral column and spinal cord in children. Reasons and
      consequences of diagnostic delay].
AB  - INTRODUCTION: Primary or secondary tumours of spinal cord and vertebral column
      have various histological structure, various degree of malignancy and various
      growth dynamics. Such localisation of neoplastic disease creates problems,
      connected with the risk of irreversible damage of neurological functions. It is
      essential to make a proper diagnosis very early. AIM: An analysis of initial
      clinical symptoms and reasons for diagnostic delay in children with neoplasms of
      the vertebral column and spinal cord. This can facilitate and accelerate
      diagnostic and therapeutic process. MATERIAL AND METHODS: 20 children treated
      from 1994 to 2004 in Department of Paediatrics, Haematology, Oncology and
      Endocrinology in the Medical University of Gdansk, were investigated. Patients
      were divided into 2 groups. In group I, there were 11 children with neuroblastoma
      and peripheral primitive neuroectodermal tumour (PNET). The primary focus of the
      neoplasm was localised beyond the vertebral column with secondary infiltration of
      the spinal cord. Nine children were included in-group II, with primary focus in
      the spinal cord: glioma (2), ependymoma (1), meningioma (1) and localised in
      bones of the vertebra: osteosarcoma (2), chondrosarcoma (1), Ewing sarcoma (1)
      and those eosinophilic granuloma (1). Patients were admitted to hospital late. In
      group I, advanced stage of disease (III and IV) was found in 5, and stage IV in 6
      children. In the early stage of the disease in-group II, pain and neurological
      symptoms were predominant. Duration of symptoms was longer than in-group I. It
      was from 6 weeks to 12 months. In both groups diagnostic delay was noted in 13
      out of 20 patients. RESULTS: In spite of using obligatory treatment protocols
      diagnostic delay contributed to permanent neurological complications in 65% of
      patients.

PMID- 15738594
TI  - [Wilms' tumour of unfavorable histology--results of treatment with the SIOP 93-01
      protocol at the Gdansk centre. Preliminary report].
AB  - BACKGROUND: Wilms' tumour is the most common primary renal tumour of childhood.
      The aim or the study was to evaluate the results of treatment in patients with
      unfavourable histology Wilms' tumour. MATERIAL AND METHODS: 44 children were
      treated for nephroblastoma (Wilms' tumour) according to the SIOP 93-01 protocol
      in the Department of Paediatrics. Haematology. Oncology and Endocrinology,
      Medical University of Gdansk, between 1993 and 2002. Eleven children were
      classified as having tumours with high-grade malignancy. Among these 2 cases of
      nephroblastoma with diffuse anaplasia, 6 with sarcomatous stroma and 2 cases with
      clear cell sarcoma of the kidney were diagnosed. In one patient file tumour
      structure was undefined due to complete necrosis of the tumour tissue. The
      staging stratification was as follows: stage I-l, II N (-)-l, II N (+) -3, III-
      6, including a neoplasmic occluding thrombus in the inferior vena cava, IV - 0, V
      0. All children were treated according to the SIOP 93-01 protocol. RESULTS:
      complete remission was achieved in 9 patients. Two children died. Fatal outcome
      was attributed in one case to cancer progression (primary resistance to
      chemotherapy after 14 months of treatment) and in the other, to the treatment
      complications (fungal sepsis after undergoing the third course of chemotherapy
      Carbo+ VP-16). In the analysed group there were no patients with stage IV
      disease, no relapses were observed. CONCLUSIONS: our observations support the
      opinion, that high-grade malignancy histology is the basic unfavourable
      prognostic factor in nephroblastoma.

PMID- 15738593
TI  - [Stage IV Wilms' tumour -- analysis of treatment results, according to the SIOP
      93-01 protocol, at the Medical University of Gdansk].
AB  - THE AIM OF THE STUDY: To evaluate the results of treatment in patients with
      Wilm's' tumor in stage IV at the Gdansk Medical University Centre. MATERIAL AND
      METHODS: Between 1993 and 2002, 44 children with nephroblastoma were treated
      according to SI0P 93-01 protocol, in the Department of Paediatrics, Haematology,
      Oncology and Endocrinology of the Medical University of Gdansk. Stage IV tumour
      was confirmed in 6 children: 3 boys and 3 girls. Metastases into the lungs were
      identified in 4 patients, into the lungs and liver in l child and into the right
      atrium wall in l child. RESULTS: After preoperative chemotherapy complete
      regression of metastases was obtained in 3 patients. Partial regression was
      obtained in 2 patients. In l patient there was no effect of preoperative
      treatment. In all patients nephroblastoma of intermediate histological risk was
      diagnosed. Among the 6 analysed patients with stage IV of the disease, 5 children
      are alive. Time of observation is from 42 to 102 months. 1 child died from
      treatment complications: necrotising enteritis.

PMID- 15738595
TI  - [5- year old boy with Weber-Christian Syndrome or histiocytic cytophagic
      panniculitis? Diagnostic difficulties. Case presentation].
AB  - The aim of the paper is to present a case of a 5-year-old boy hospitalised
      because of recurrent high temperature and reddish blue infiltration of skin and
      hypodermis lasting 3 months. Because of pancytopenia and hepatomegaly, we
      suspected a proliferative disease of the haematopoietic or lymphatic system.
      Several bone marrow biopsies, did not show neoplastic changes. Serological tests
      excluded virus and animal borne infections. In the histopathologic examination of
      skin and hypodermis biopsy there was an inflammatory infiltration of the adipose
      tissue without features of vessel inflammation (the Weber-Christian syndrome). Al
      though steroid therapy was applied, the infiltration of the adipose tissue did
      not regress, while liver dysfunction symptoms intensified and pancytopenia and
      fever continued. The patient died with symptoms or respiratory and circulatory
      failure. This case of a 5-year-old boy is presented because of extreme diagnostic
      difficulties, which occurred at each phase of investigations. The repeated tests,
      as well as several verifications of the sampled histopathological material did
      not bring any unequivocal proof of the postulated diagnosis.

PMID- 15738596
TI  - [Haemangiomas and diffuse neonatal haemangiomatosis].
AB  - Haemangiomas are the most common benign tumours of infancy. However, diffuse
      neonatal haemangiomatosis is a rare disorder with a high mortality characterized
      by multiple haemangiomas affecting the skin and visceral organs. A case of
      diffuse neonatal haemangiomatosis in a newborn child is described and current
      opinions on haemangiomas in the literature are reviewed.

PMID- 15738598
TI  - [Biochemical bone resorption markers in children with osteosarcoma].
AB  - Biochemical markers of bone resorption such as the bane collagen breakdown
      products and specific factors associated with osteoclastogenesis are useful for
      monitoring the response of anticancer therapy and to assess disease progression
      in patients with metastatic bone disease. AIM: the aim of present study was to
      assess bone resorption process by collagen type I crosslinked C-telopeptide and
      osteoprotegerin levels in children with osteosarcoma. SUBJECTS AND METHODS: in
      serum of 20 patients (10-19 years) with osteosarcoma, bone resorption markers
      were determined: at diagnosis (before treatment), during preoperative and
      postoperative chemotherapy and after treatment. The control group consisted of 15
      healthy age-matched children. Bone resorption markers were measured by
      immunoenzymatic ELISA assays. RESULTS: mean serum concentration of collagen type
      I crosslinked C-telopeptide in patients at the time of diagnosis was 15206 +/-
      6808 pM/L. then it decreased by 15% during preoperative chemotherapy and it
      increased during the postoperative chemotherapy. In addition, the mean
      osteoprotegerin level was 3.73 +/- 0.78 pM/L at diagnosis, it increased by 12%
      during preoperative chemotherapy and then it decreased during the postoperative
      phase. Patients after therapy were divided into two subgroups: with favourable
      and unfavourable prognosis, In patients with favourable prognosis we observed
      lower serum concentrations of both resorption markers in comparison to patients
      with poor prognosis. CONCLUSIONS: bone resorption markers: may be useful for
      assessing bone resorption process and can be used in diagnosis and monitoring
      therapy of patients with osteosarcoma. Higher serum concentration bone resorption
      markers (especially osteoprotegerin) may be related to poor prognosis.

PMID- 15738597
TI  - [Imbalance between pro-oxidative and anti-oxidative processes in children with
      neoplastic disease].
AB  - THE AIM of the study was to assess the concentration of malondialdehyde (MDA),
      vitamin E and total antioxidant status (TAS) of serum and activity of superoxide
      dismutase (SOD) and glutathione peroxidase (GPX) in erythrocytes. MATERIAL AND
      METHODS: a total of 56 children, aged 1,5-18 years, treated between 2001-2002,
      were diagnosed as having malignant disease. Of these, 27 patients had leukemia,
      20 had solid tumours and 9 -lymphoma. These patients were examined before
      treatment and on achieving remission during therapy. RESULTS: the imbalance
      between pro-oxidative and antioxidative processes were found in all the children
      with neoplastic disease. TAS was lower and GPX was higher than normal in all
      children with cancer; MDA was higher in the newly diagnosed children before
      treatment. CONCLUSIONS: the role of vitamin E in the pathogenesis of childhood
      neoplastic disease need to be evaluated. Further studies on a larger group of
      patients are needed.

PMID- 15738599
TI  - [Markers of bone formation in children with osteosarcoma].
AB  - Among biochemical markers, which reflect bone remodeling and can be measured in
      blood, there are formation markers such as serum bone alkaline phosphatase (BALP)
      and osteocalcin (OC). Formation markers are considered to be useful in diagnosis
      and anticancer treatment of many metastatic bone diseases, but the clinical value
      of these markers in primary osseous tumours such as osteosarcoma is not yet
      recognized. AIM: The aim of this study was the investigation of BALP activity and
      OC level in patients with osteosarcoma during clinical treatment. SUBJECTS AND
      METHODS: We studied 22 patients (aged 11-19 years) with osteosarcoma, at
      diagnosis, during preoperative and postoperative chemotherapy and at the end of
      treatment. The control group consisted of 30 healthy age-matched children. The
      activity of BALP and the level of OC were measured in serum using ELISA kits.
      RESULTS: Our results indicated that both tested parameters were lower during
      preoperative and postoperative chemotherapy (BALP, p<0.05; OC, p<0.01,p<0.001),
      in patients group than in controls. However we found higher value of BALP and OC
      also at diagnosis and during chemotherapy in same patients before occurrence of
      metastases. Moreover, we observed markedly higher activity of BALP (5:fold) and
      level of OC (2-fold) in patients with progression in comparison to the group with
      favourable prognosis, who responded to chemotherapy. CONCLUSIONS: Our studies
      suggest, that investigation of formation markers, especially BALP could be useful
      in monitoring of osteosarcoma therapy and may be a valuable indicator of the
      progression of this disease. Further studies with long-term observation of
      investigated patients are necessary.

PMID- 15738600
TI  - [Increased frequency of A-G transition at exon 5 of GSTP1 as a genetic risk
      factor for acute childhood leukaemia].
AB  - Polymorphism of genes encoding glutathione S-transferases GSTM1, GSTT1 GSTP1 is
      one of the genetic predictors of susceptibility to cancers in the adults. The
      frequency of deletions of GSTM1. GSTT1 genes and transition A-G in GSTP1 gene
      were taken into consideration. THE AIM of this study was to investigate the role
      of GST genes polymorphisms as a genetic risk factor for acute lymphoblastic
      leukaemia (ALL), and to study the relationship of these polymorphisms with
      clinical outcome in childhood leukaemias. MATERIAL AND METHODS: 86 children with
      newly diagnosed acute leukaemia (female: male ratio = 37:49. median age = 7.8
      years) and 460 healthy controls were examined using the PCR and PCR-RFLP methods
      to identify polymorphisms within GSTM1, GSTT1 and GSTP1 genes. In the group of
      children with ALL. the frequency of relapses, deaths, clinical course,
      immunophenotype of blasts and the initial response to prednisone were also
      analyzed. RESULTS: the higher frequency of A-G transition in the GSTP1 gene was
      identified in the group of children with ALL in comparison to healthy controls
      (OR=3.13, 95%CI=1.4-7). We also found that the combination of GSTPl (Val/Val) and
      GSTM1 null genotypes further increased the risk of ALL (OR= 10.63, 95%CI=3.47 -
      32.58; p =0.0001). No differences in the frequency of GSTM1 and GSTTI genes
      between both groups (OR=1; 95%CI=0,59-1,74 and OR=0, 71; 95%CI=0.45-1.13
      respectively) were observed. Statistical analysis has not revealed any
      connections between polymorphisms within glutathione S-transferases genes and the
      frequency of relapses and death or poor initial response to prednisone. However,
      the biphenotypic immunophenotype or B-line blasts were the risk factors of
      relapse or death of progression in ALL (p=0.03). CONCLUSION: transition in exon 5
      of GSTP1 gene (alone or combined with GSTM1 deletion) may be one of the molecular
      predictors of higher susceptibility to acute leukaemia in children. but not of
      the clinical course of this disease.

PMID- 15738601
TI  - [Diagnostic significance of reticulocyte analysis by flow cytometry, in children
      with acute lymphoblastic leukaemia (ALL) on chemotherapy].
AB  - INTRODUCTION: Reticulocytes and their fractions quickly show changes at the time
      of chemotherapy, therefore they can be an early indicator of changes arising in
      the erythrocytic line. THE AIM: of the study was an assessment of percentage,
      absolute number and immature reticulocyte fraction (IFR) by flow cytometry in
      children with acute lymphoblastic leukaemia (ALL) and comparing them with
      classical indexes of the erythrocyte line. MATERIAL AND METHODS: The examined
      group of 14 children from 2 to 16 years with ALL, on remission support treatment
      (New York II protocol). RESULTS: The group which was treated by thioguanine and
      cyclophosphamide showed reduction of reticulocytes from mean value 3,1+/-1:1,4 to
      2,5+/-1,8. IFR reduction was not significant statistically. In the group treated
      with vincristine and methotrexate an average percentage of reticulocytes fell
      from 3.5+/-O.8 to l,5+/-0,4 and IFR did not change significantly. In children who
      were treated by daunorubicin and cytosine arabinoside an average percentage of
      reticulocytes reduced from 3.2+/-O,8 to value 2,1+/-1, 7. The immature
      reticulocyte fraction (IFR) reduced significantly from 22,0+/-6,0 to 12,0+/-8,0
      (p<0,03). CONCLUSIONS: The indicators of reticulocytes were reduced after each
      cycle chemotherapy: this indicates damage in the erythrocyte line. The indicators
      examined by cytometric method can show changes earlier than classical indicators
      used in haematology.

PMID- 15738602
TI  - [Relationship between the expression of insulin-like growth factor I receptors
      and apoptosis after preliminary chemotherapy, in child and adolescent
      osteosarcoma].
AB  - INTRODUCTION: The influence of growth factors and apoptosis on the clinical
      course of neoplasms is of significant interest for oncologists, especially
      neoplasms with dynamic changes in proliferation, such as child and adolescent
      osteosarcoma. AIM: To investigate reciprocal relations between the expression of
      insulin-like growth factor I receptors (IGF-IR) and index apoptosis ("pre-G l /G
      0" fraction, DNA histograms) in osteosarcomas before operation and after
      preliminary chemotherapy. MATERIAL AND METHODS: Flow cytometric analysis was
      carried out in 20 children and adolescents with osteosarcoma (aged 6 to 18 years)
      after preliminary chemotherapy. The material for investigation was taken during
      surgery. RESULTS: It was shown that higher expression of IGF-IR is associated
      with lower apoptosis index (% of apoptotic cells) and reversely (significant
      difference p<O, 05 Student's test). CONCLUSIONS: Investigations of the above
      relations are significant for better understanding of the influence of IGF-IR on
      the disease course and on the preliminary evaluation of cytostatic activity by
      way of apoptosis initiation.

PMID- 15738603
TI  - [Cytometric analysis of the relation between aneuploidy and expression of
      receptors for insulin growth factor I in child and adolescent osteosarcoma, after
      preliminary chemotherapy].
AB  - INTRODUCTION: Aneuploidy cell population is often seen as a marker of malignancy.
      The influence of growth factors on this cell population is of interest for
      oncologists, in the context of the clinical course of disease and the results of
      therapy. AIM: To investigate of reciprocal relations between aneuploidy
      parameters and expression of receptors of insulin-like growth factor I (IGF-IR)
      in osteosarcomas after preliminary chemotherapy. MATERIAL AND METHODS: Flow
      cytometric analysis was carried out in 20 children with osteosarcoma (aged 6 to
      18 years) after preliminary chemotherapy. Biopsy material was taken during
      operation. RESULTS: It was shown, that higher aneuploid fraction and DNA index
      correlate with higher IGF-IR expression (significant difference p<O, 05). It may
      influence the sensitivity of osteosarcoma with higher aneuploidy fraction on the
      IGF-1, and in consequence may result in increasing proliferation. CONCLUSIONS:
      The suggestion concerning higher susceptibility of osteosarcoma's with higher
      aneuploidy on IGF-1 should be verified by longer clinical observation concerning
      survival rate in the two groups; the group with higher and the group with lower
      aneuploidy and IGF-IR expression.

PMID- 15738604
TI  - [Vitamin B(12) deficiency anaemia in a 7.5 months old girl].
AB  - Vitamin B(12) stores at birth are adequate for infants until the end of the first
      year of life even if it 's concentration in maternal breast milk is low. However,
      there are some situations in which infants have depleted vitamin B(12) stores and
      in addition have a low dietary intake of cobalamin. Vitamin B(12) depletion
      occurs in infants who are exclusively breastfed by mothers who have unrecognized
      pernicious anemia or are strict vegetarians for many years. In those infants
      symptoms of bone marrow disfunction and impaired development of the central
      nervous system appear already in the first months of life. Unrecognized cobalamin
      deficiency may lead to serious neurologic consequences, and even to the death of
      the child. The authors present a case of a 7.5 month old girl admitted to the
      Department of Paediatrics, Haematology, Oncology and Endocrinology. Gdansk
      Medical University suspected of acute leukaemia. Based on a detailed diagnostic
      procedure a final diagnosis of vitamin B(12) deficiency anaemia was established.
      The child was exclusively breast-fed. Results of investigations into the reason
      for cobalamin deficiency in the patient s organism. Led to the diagnosis of
      pernicious anaemia in the mother. Such a suspicion had been made during
      pregnancy, but no continuation of investigations nor appropriate treatment were
      implemented. After treatment with vitamin B(12) supplements and modification of
      the diet the patient improved quickly and remarkably. A few months follow-up was
      enough to observe remarkable improvement of psychomotor development of this
      child.

PMID- 15738605
TI  - [Nephrotoxicity of ifosfamide with special reference to Fanconi Syndrome].
AB  - The article is a case presentation of Fanconi syndrome in a patient treated with
      high doses of ifosfamide. ifosfamide nephrotoxicity relates to glomerular and
      tubular disfunction. Tubular disfunction type 2 (Fanconi Syndrome) is observed
      most often. In this syndrome hypophosphatemia, hyperphosphaturia, glucosuria,
      polyuria, aminoaciduria, hypokalemia and tubular acidosis are present. The
      treatment consists of electrolyte supplementation and acidosis reduction.
      Nephrotoxicity risk factors are: total ifosfamide doses and age under 3 years.
      Early diagnosis is possible by estimating b2 microglobulin and retinal binding
      protein. Normally used parameters of renal function are insufficient. MATERIAL
      AND METHODS: case report - N. W - 13-year-old patient with a skin's tumour was
      treated in our clinic. Euro Ewing-99 protocol with 100.8 g/m2 of ifosfamide was
      applied for 18 months. During treatment serum electrolytes, urea, creatinine and
      creatinine clearance were normal. 6 months after treatment a metastasis in the
      lung was detected. RESULTS: Fanconi Syndrome symptoms were noticed before
      introduction of chemotherapy. After treatment with small doses of ifosfamide (4.5
      g/m2) the disorders became severe. For this reason, nephrotoxic cytostatics were
      excluded from further treatment, decreasing its efficiency. CONCLUSIONS: 1. Renal
      complications of ifosfamide may appear after treatment completion. Monitoring of
      renal function parameters is necessary during and after treatment. 2. When
      protocols with cyclophosphamide (less nephrotoxic than ifosfamide) prove to be of
      similar efficiency, this treatment could be an alternative for patients' with
      renal disfunction. 3. Patients with completed ifosfamide treatment shall be
      qualified for repeated chemotherapy carefully due to high-risk of renal
      disfunction.

PMID- 15738606
TI  - [Effect of anticancer treatment on leptin level, fat body mass (FM) and lean body
      mass (LBM)].
AB  - Leptin plays an important role in the metabolism of adipose tissue. Considering
      that malignancy and its treatment cans affect normal development in childhood. We
      analysed the correlations between serum leptin levels and body composition after
      anticancer treatment. We studied 33 survivors (24 boys and 9 girls) who before
      our study, have been treated for acute lymphoblastic leukaemia (ALL) (n=23) and
      Hodgkin disease (n=10) after 7.15+/-3.5 years. Sixteen patients with ALL received
      cranial irradiation (12Gy). We measured body mass index (BM1) fat mass (FM) and
      lean body mass (LBM) using dual energy x-ray absorptiometry (DXA). We compared
      these results to the results obtained from reference values (SD score). Leptin
      levels were measured with the RIA method. RESULTS: 1. Mean leptin levels were
      higher in girls after puberty (10.93 ng/mL+/-8.9) than in boys (3.73 ng/mL+/-3.
      7). In boys no differences were found in leptin levels between T2-4 and T5
      stages. In girls the leptin values increased after puberty. Leptin SD score
      levels were higher in boys during (1.55 +/-1.0) and after puberty (1.46+/-0.75)
      and in girls - after puberty (1.19 +/-1.51). We did not find any influence of
      cranial irradiation (12Gy) or various methotrexate doses (5 g/m(2) vs. 19/m(2))
      leptin values. 2. No difference in BMI SD score was found within the whole study
      group. 3. FM did not change ill boys during and after puberty, although FM SD
      score were higher during puberty (2.98 +/-4.8). In girls FM and FM SD score were
      higher after puberty. In boys and girls LBM augmented with pubertal development
      but LBM SD score in boys were lower after puberty (-1.67 +/-1.7) in comparison to
      puberty (0.2 +/-1.7). No differences were found between LBM SD score in girls
      during and after puberty. 4. We found a correlation between leptin levels and BMI
      (r=0.59 p=0.001) and FM (r=0.77 p=0.0001). 5. Relation of FM to LBM in boys
      remained unchanged, however in girls it increased within pubertal development.
      CONCLUSION: l. Anticancer treatment during childhood shows no influence on body
      mass index although the tendency to higher fat mass in pubertal boys and in post
      pubertal girls is observed. 2. Leptin values depend on fat mass and do not relate
      directly to the pubertal stage.

PMID- 15738607
TI  - [Preoperative high-dose brachytherapy in cases of endometrial carcinoma-
      preliminary assessment of outcomes and safety].
AB  - INTRODUCTION: Rising incidence of endometrial carcinoma provokes searching for
      the best and the safest treatment method. MATERIALS AND METHODS: We included in
      our observation 35 patients suffering from gynaecologic malignancies. They had
      been treated in H. Jordan s Memorial Hospital. Institute of obstetrics and
      Gynaecology of the Medical Academy in Lodz and in the Polish Mother's Memorial
      Hospital-Research Institute, co-operating with the Gynaecologic Radiotherapy
      Department. The intracavitary method of treatment is described, emphasising the
      need of precise patients' qualification for this procedure. The importance of MRI
      as a diagnostic procedure is stressed. All patients were referred for surgical
      procedures including regional lymph nodes removal 6 weeks after completion of the
      brash therapy treatment. Pan hysterectomy was performed in 30 cases. 5 patients
      refused surgical treatment. RESULTS: In the majority of patients (18) the
      histological examination of specimen (uterus. ovaries, and lymph nodes) was free
      from cancer cells. These patients did not require further whole pelvis
      irradiation. CONCLUSIONS: In our material preoperative brachytherapy procedure
      allowed to avoid whole pelvis irradiation in more than half of the patients. This
      procedure is also cost effective as patients avoid long-time hospitalisation
      combined with teleradiotherapy. It is also worth to stress that patients avoid
      complications related to teleradiotherapy of the pelvis as well as long term
      treatment and rehabilitation.

PMID- 15738608
TI  - [Conservative treatment of ectopic pregnancy in a 27 years old patient with stage
      Ia ovarian cancer after conservative surgical treatment and chemotherapy].
AB  - We report a case of conservative treatment of ectopic pregnancy in a 27 years old
      patient, previously treated for ovarian cancer. Two years before she had surgery
      because of tumour in the left ovary. Ovarian cancer in stage la according to FIGO
      was confirmed. Considering the patient s young age, future reproductive plans and
      the early stage of cancer, the patient qualified for conservative treatment. Left
      adnexectomy with consequent chemotherapy (6 courses) was performed. Two years
      later on the ground of clinical symptoms, gynaecologic examination, sonography
      and changes in HCG serum concentration, ectopic pregnancy was recognised in the
      right tube. We applied conservative management with intramuscularly administrated
      Methotrexate. The patient, in good condition, was discharged from hospital on day
      12 after injection of Methotrexate.

PMID- 15738609
TI  - [Healthy siblings of children with cancer. The model of psychosocial care].
AB  - The presence of childhood cancer threatens the balance of the entire family.
      Perhaps the most profoundly affected are the healthy siblings, who experience
      significant psychosocial distress at home as well as at school. They suffer from
      a lack of knowledge about their brother's or sister's disease, feelings of
      abandonment, anger; resentment, sadness and guilt. In the study the factors
      associated with these issues and psychological adjustment to childhood cancer
      were investigated. Well Siblings Situation Scale was created to estimate the
      probability of the occurrence of psychosocial problems in this group of otherwise
      healthy children. The scale covers the risk factors described in terms of
      demographic, family, disease related and personal characteristics. The proposed
      model of psychosocial intervention includes repetitive use of the Well Siblings
      Situation Scale to identify the dysfunctional group of siblings. The program of
      psychosocial care will facilitate the healthy siblings' adjustment to the cancer
      experience with a focus on promoting more successful coping and managing the
      stress of a life threatening illness. This can be an effective approach for
      providing basic information on cancer and its treatment. More important, various
      forms of individual and group care will allow lo share the feelings of paediatric
      cancer patients and express their special concerns in a supportive and
      therapeutic environment. The programme will include parents, teachers, health
      care professionals, and most of all the siblings.

PMID- 15738610
TI  - G6PD deficiency in Vataliya Prajapati community settled in Surat.
AB  - BACKGROUND: A Study on Vataliya Prajapati was published earlier but heterozygous
      females were not identified. AIMS: To compare incidence of glucose-6-phosphate
      dehydrogenase (G6PD) deficiency in random and unrelated subjects, present and
      previous study and as per their original habitat. Incidence of heterozygous
      deficiency and clinical implication of deficiency was also determined. SETTINGS
      AND DESIGN: Camps were organized in Katargaon and Amroli regions. Blood
      specimens, with relevant demographic information, were collected from those who
      attended the camp. METHODS AND MATERIAL: A total of 1644 random blood samples
      were collected from 404 families participating in the camps. Nitroblue
      tetrazolium dye test was used for G6PD deficiency screening and quantitative
      assay for measurement of G6PD enzyme activity. STATISTICAL ANALYSIS USED: Chi2
      test was used to evaluate significance and mean values were compared by the
      Student's ''t'' test. RESULTS: Incidence of G6PD deficiency was found as 22%
      among all the random samples tested. However, the G6PD deficiency among unrelated
      members was 27.9% in males and 12.4% (P< 0.001,df 1). The 13.9% of the females
      with heterozygous G6PD deficient status, together with the homozygous deficient
      phenotype makes the incidence comparable with males. Incidence of deficiency was
      comparable with previous study, in Katargam and Amroli and in Amerli and
      Bhavganar districts. Deficient subjects had mild anemia and hemolytic crisis
      rarely occurred. CONCLUSION: Vataliya Prajapatis have high incidence of G6PD
      deficiency without severe chronic hemolytic anemia. However before prescribing
      medicines physician should know the G6PD status of a Vataliya Prajapati patient.

PMID- 15738611
TI  - Maternal thyroid hormonal status in preeclampsia.
AB  - BACKGROUND: The physiological changes in the thyroid gland during pregnancy are
      well understood but only a few reports provide information about thyroid function
      in complicated pregnancies. AIMS: The present study evaluates thyroid hormonal
      levels in cases of preeclampsia in the third trimester of pregnancy. SETTINGS &
      DESIGN: A case-control study was conducted in the antenatal clinic of a public
      hospital of Delhi. METHOD & MATERIALS: Thyroid hormones, namely triiodothyronine
      (Free T3), thyroxine (Free T4) and thyroid stimulating hormone (TSH) were
      evaluated at the time of diagnosis of preeclampsia in 82 pregnant women and equal
      number of matched controls. STATISTICAL ANALYSIS: The demographic data and
      hormone levels were analyzed using students' t test, Mann-Whitney test and chi
      square test. Pearson two-tailed analysis was used for correlation. RESULTS: Mean
      TSH levels were significantly higher in preeclamptic group as compared to
      controls (p< 0.001). However, mean values of thyroid hormones were in the normal
      range. Approximately 40% preeclamptic women had TSH titres > 5 mIU/ml in the
      study group as compared to 12.2% in the controls. Approximately 76.7% of 43
      pregnant women with abnormal TSH titres and 40% of 121 pregnant women with normal
      TSH titres belonged to the study group (p< 0.001). The odd ratio corresponding to
      TSH titres > 5 mIU/ml in preeclamptic women was 4.85 (95% CI 2.19-10.74).
      CONCLUSIONS: Mean serum TSH levels were significantly increased without
      concomitant changes in free T3 and T4, in preeclampsia compared to normal
      pregnancy. Abnormal TSH titres might be associated with a risk for occurrence of
      preeclampsia.

PMID- 15738612
TI  - Effect of fenugreek, onion and garlic on blood glucose and histopathology of
      pancreas of alloxan-induced diabetic rats.
AB  - BACKGROUND: Many traditional treatments have been recommended in the alternative
      system of medicine for treatment of diabetes mellitus; however, the mechanism of
      most of the herbals used has not been defined. AIMS: This study was carried out
      to clarify the effect of fenugreek, garlic and onion, recommended in Persian
      folklore medicine as beneficial in the treatment of diabetes, on blood glucose
      and their possible effect on pancreatic tissue. METHODS AND MATERIAL: Diabetes
      mellitus was induced in 20 out of 25 adult male albino rats, using
      intraperitoneal injection of 185 mg/kg BW alloxan. The diabetic rats were divided
      into four groups, three of which were fed a diet containing 12.5% BW Allium
      sativum (garlic), Allium cepa (onion) or Trigonella foenum-graecum (fenugreek)
      for 15 days. The fourth group (positive control) received an ordinary diet. The
      remaining non-diabetic rats (negative control group) received neither alloxan nor
      the mentioned plants. Following consumption of plants, blood glucose was measured
      every day and on the last day the pancreas were removed and stained with H&E and
      Gomeri aldehyde fuchsin (GAF). Morphology of the pancreatic sections and the
      following morphometric factors were studied: volume density of B cells, volume
      density of islets, percent of B cells, number of islets per square millimeter,
      average area of islets and average volume density of B cell in whole pancreas.
      STATISTICAL ANALYSIS USED: One-way Analysis of Variance (ANOVA) test and Duncan's
      multiple range tests were used to evaluate the data. RESULTS AND CONCLUSION: The
      results of this study indicate that only garlic was able to reduce blood glucose
      significantly compared with the control group (P<0.05). In the control positive
      group all the mentioned morphometric factors were significantly changed in
      comparison with the control negative (normal health) group, but the same did not
      show significant change between treated and untreated diabetics.

PMID- 15738613
TI  - Rabson-Mendenhall syndrome.
AB  - Rabson-Mendenhall syndrome is characterized by growth retardation, dysmorphisms,
      lack of subcutaneous fat, acanthosis nigricans, enlarged genitalia, hirsutism,
      premature and dysplastic dentition, coarse facial features, paradoxical fasting
      hypoglycemia and post-prandial hyperglycemia, extreme hyperinsulinemia and pineal
      hyperplasia. We describe a six-month-old female child with physical features
      suggestive of the Rabson-Mendenhall syndrome. The child also had medullary
      nephrocalcinosis.

PMID- 15738614
TI  - Validity of consent--a review of statutes.
AB  - In recent years there have been a number of malpractice suits based on lack of
      consent or inadequate consent from the patient for the procedure used in
      treatment. This is a particularly dangerous suit for the doctor since the burden
      of proof lies on the doctor. Furthermore since the suit is based on intentional
      assault, some insurance policies do not cover the doctor for his liability. The
      common meaning of consent is permission, whereas the law perceives it as a
      contract i.e. an agreement enforceable by law. So a doctor needs to understand
      the legal basis of consent rather than the common meaning of it. The present
      article aims to discuss the various legal aspects of consent as viewed in the
      Indian law.

PMID- 15738615
TI  - [Roles of the amygdala in pain-related aversive responses].

PMID- 15738616
TI  - [Distinct mechanisms underlying pleasure and analgesia].

PMID- 15738617
TI  - [Regulation of emotional behavior by nuclear receptors].

PMID- 15738618
TI  - [Molecular genetic approach to depression from animal models].

PMID- 15738619
TI  - [Polymorphism of the peripheral-type benzodiazepine-receptor gene associated with
      the trait of anxiety].

PMID- 15738620
TI  - [Raloxifene hydrochloride (Evista Tablet 60 mg) for postmenopausal osteoporosis:
      mode of action and clinical efficacy].

PMID- 15738621
TI  - Effects of in utero exposure to bisphenol A on mRNA expression of arylhydrocarbon
      and retinoid receptors in murine embryos.
AB  - To evaluate the effects of bisphenol A (BPA), a candidate endocrine disruptor
      (ED), on embryonic development, we examined the mRNA expression levels of the
      arylhydrocarbon receptor (AhR), which binds with many EDs and plays crucial roles
      in xenobiotic metabolism, and of the retinoic acid receptor (RAR) alpha and
      retinoid X receptor (RXR) alpha, key factors in nuclear receptor-dependent
      retinoid signal transduction, in murine embryos exposed in utero to BPA (0.02, 2,
      200, and 20,000 microg/kg/day) at 6.5-13.5 or 6.5-17.5 days post coitum (dpc),
      using the real-time reverse transcription-polymerase chain reaction (RT-PCR)
      method. Extremely low-dose BPA (0.02 microg/kg/day; 1/100 the dose of
      environmental exposure) remarkably increased AhR mRNA expression in the cerebra,
      cerebella, and gonads (testes and ovaries) of male and female 14.5- and 18.5-dpc
      embryos. In utero exposure to BPA at 2, 200, and 20,000 microg/kg/day also
      increased levels of AhR mRNA. In gonads of 14.5-dpc-embryos, AhR mRNA levels were
      elevated and showed diphasic (U) dose-response curves following exposure to BPA,
      but inverted U dose-response curves were obtained for 18.5-dpc-embryos. Exposure
      to BPA increased expression levels of RARalpha and RXRalpha mRNAs in the cerebra,
      cerebella, and gonads of male and female 14.5- and 18.5-dpc-embryos. Extremely
      low-dose BPA (0.02 microg/kg/day) increased RARalpha mRNA expression in the
      cerebella of male and female 14.5- and 18.5-dpc-embryos and in the gonads of
      female 14.5-dpc-embryos, and significantly increased RXRalpha mRNA expression in
      the cerebra and cerebella of male and female 14.5-dpc-embryos. The present
      findings confirm that in utero exposure to an extremely low dose of BPA up
      regulates the mRNA expression of AhR, RARalpha, and RXRalpha in murine embryos
      and disrupts the receptor-dependent signal transducing systems, and will
      contribute to the assessment of the toxic effects of BPA on xenobiotic metabolism
      and retinoid signals in embryogenesis.

PMID- 15738622
TI  - Immunolocalization of nerve growth factor (NGF) and its receptors (TrkA and
      p75LNGFR) in the reproductive organs of Shiba goats.
AB  - The objective of this study was to determine the immunolocalization of NGF and
      its receptors (TrkA and p75LNGFR) in the reproductive tract of the Japanese Shiba
      goats. Five adult goats were used in this study and sections of ovaries, uteri
      and oviducts were immunostained by the avidin-biotin-peroxidase complex method
      (ABC). The results showed that NGF and its receptors (TrkA and p75LNGFR) were
      expressed in granulosa cells, theca cells, interstitial cells and lutein cells in
      ovaries. Immunoreactions for NGF, TrkA and p75LNGFR were also detectable in
      epithelial cells and muscle cells of the ampulla and isthmus of the oviduct, and
      in epithelial cells and uterine glands of the uterus. These results strongly
      suggest autocrine and paracrine regulation of reproductive function by NGF in the
      reproductive tract of female Shiba goats.

PMID- 15738623
TI  - [Chemical study of citrus plants in the search for cancer chemopreventive
      agents].
AB  - The constituents of Citrus plants were investigated to develop useful agents that
      are effective in cancer chemoprevention. We examined the roots and bark of the
      roots of various Citrus plants, resulting in the isolation of many novel
      compounds. Their structures were determined using spectroscopic methods,
      especially 2D-NMR spectra. The following new compounds of constituents were
      found: dimeric coumarins, dimeric acridone alkaloids, and acridone-coumarin
      dimers. Auraptene and nobiletin are known as useful constituents of the peel of
      Citrus plants for cancer chemoprevention. However, we found that 3,5,6,7,8,3',4'
      heptamethoxyflavone (HPT) has both antitumor promotion and initiation activities
      and is more effective than auraptene and nobiletin. We synthesized pentaallyl
      quercetin (QPA), a useful antitumor compound that has the additional effects of a
      P-glycoprotein (P-gp) inhibitor. The inhibitory effects of QPA on P-gp were more
      effective than those of the typical P-gp inhibitors cyclosporin A and verapamil.
      Both HPT and QPA have antitumor promotion activity and are potential candidates
      for effective multidrug resistance agents in cancer chemotherapy.

PMID- 15738624
TI  - [New findings on the structure-phototoxicity relationship and photostability of
      fluoroquinolones].
AB  - The present study examined the phototoxicities of a series of 7-(3
      aminopyrrolidinyl) quinolones containing various substituents at position 1 by
      use of a mouse model. For the 7-(3-aminopyrrolidinyl) quinolones with a halogen
      atom at position 8, well-known substituent groups such as a cyclopropyl, an
      ethyl, or a difluorophenyl at position 1 were found to be responsible for severe
      phototoxicity. However, when an aminodifluorophenyl or an isoxazolyl group was
      placed at position 1, even 8-halogeno quinolones were found to be mildly
      phototoxic. This is the first report of 8-halogeno quinolones that are not
      severely phototoxic. Two structurally similar 8-chloro quinolones (the 1
      aminodifluorophenyl 8-chloro quinolone and the 1-difluorophenyl 8-chloro
      quinolone) were investigated further. The former was mildly phototoxic; the
      latter was severely phototoxic. We demonstrate that these two 8-chloro quinolones
      have practically the same areas under the concentration-time curves from 0 to 4 h
      in auricular tissue, suggesting that the mild phototoxicity is not due to
      pharmacokinetic instability. The rates of UV photodegradation of these compounds
      were also measured. We found that these two quinolones photodegrade at similar
      rates, suggesting that the mild phototoxicity is not attained through increased
      photostability. In conclusion, the phototoxic potentials of fluoroquinolones are
      influenced not only by the substituent at position 8 but also by that at position
      1. We also discovered a mildly phototoxic 8-chloro quinolone which did not have
      increased photostability.

PMID- 15738625
TI  - [Synthesis of peptidocalix[4]arene libraries and their application to the
      development of chemical sensors for oligopeptides].
AB  - Calix[4]arene libraries consisting of ca. 50000 members substituted with peptides
      at the lower rim were synthesized using encoded spilt synthesis with 15 amino
      acids. Screening of the library for binding with a dye-labeled oligopeptide
      indicated that some peptidocalix[4]arenes selectively bind the oligopeptide. The
      binding constant was estimated to be approximately 2 x 10(4) mol dm(-3). In an
      attempt to develop chemical sensors for peptides, fluorescence-labeled
      peptidocalix[4]arene libraries consisting of ca. 3500 members were synthesized.
      The fluorescence spectrum of peptidocalix[4]arene, which was found in the
      screening of libraries against the target peptide, was dependent on the
      concentration of the peptide. The libraries substituted at the upper rim were
      also synthesized with the aim of developing more selective and sensitive chemical
      sensors. The binding selectivity of the library members for the target peptides
      was higher and the behavior of the sensing was markedly different from the lower
      rim-modified peptidocalixarene sensor.

PMID- 15738626
TI  - Pharmaceutical terms reflecting the change in practice in Japan.
AB  - The implementation of Iyaku Bungyo, the changed regulations for drug distribution
      and the proposed change of pharmacy education from a four-year program to a six
      year program are rapidly changing the practice of pharmacy. However, pharmacists'
      activities still remain at the level of simple dispensing and selling of drugs.
      Also, the terms that describe the essence of pharmacists' activities, such as
      services in patient care areas are still unclear. In order to solve and improve
      the problem of terminology for pharmacists' activities the use of terms related
      to pharmacists' services were examined in historical context. It was found that
      the terms "Rinsho yakugaku" and "Iryo yakugaku" have been used as having a
      similar meaning. Further, the term "Iryo yakugaku" was used to denote the
      comprehensive scope of pharmacists' services including "Rinsho yakugaku". It was
      verified that "Rinsho yakugaku" is a valid translation for "clinical pharmacy".
      "Iryo yakugaku" has a more comprehensive translation than "pharmaceutical care",
      therefore, it appears that "Iryo yakugaku" is a suitable translation for
      "pharmaceutical services". Hence, we proposed "Iryo yakugaku" as the English
      translation for "pharmaceutical services" and "Chiryo yakugaku" as the Japanese
      translation for "pharmaceutical care". There is a need, however for further
      clarification and definition of pharmacists' activities.

PMID- 15738627
TI  - The case for a shift in pharmacists' activities and pharmacy education.
AB  - In Japan, pharmacists' activities for the most part consist of dispensing
      although in some University Hospitals they are directly involved in patient care.
      In the United States, pharmacists' activities have evolved over forty years in
      providing drug therapy and have now expanded to improvement in the patient's
      quality of life. In addition, a six-year pharmacy education program based on
      patient care is now in place nationally. Furthermore, World Health Organization
      (WHO) and International Pharmaceutical Federation (FIP) have made recommendations
      on pharmacists' activities. Shifting to a six-year pharmacy education in Japan
      has now been decided, and new approaches are being proposed. For pharmacists to
      serve society in their role as health care professionals, one needs to examine
      the activities they are expected to perform and pharmacy education necessary to
      develop these skills. In this paper, pharmacy education was examined by analyzing
      and comparing Western countries and Japan, with a focus on Canadian pharmacists'
      activities and pharmacy education in Alberta.

PMID- 15738628
TI  - [Examination of the escape phenomenon in disease modifying antirheumatic drugs].
AB  - Although disease-modifying antirheumatic drugs (DMARDs) are used in the treatment
      of rheumatoid arthritis (RA), the selection of agents in the case of relapse
      (escape phenomenon) lacks clear-cut standards. Therefore we investigated the rate
      and conditions of escape as well as the agents used after escapes had occurred.
      Outpatients of the Matsubara Mayflower Hospital with a history of DMARD
      administration during the 4 years prior to May 2003 were studied. Those receiving
      salazosulfapyridine (SASP) had a high escape rate and those receiving
      methotrexate (MTX) and bucillamine (BC) had a low rate. The continuous duration
      of administration was long for MTX and BC, but short for sodium aurothiomalate
      (GST). BC and Actarit (AR) gradually elevated C-reactive protein (CRP) levels and
      the erythrocyte sedimentation rate (ESR). In patients receiving SASP and MTX, a
      high level of CRP and high ESR was seen 2 months prior to the occurrence of
      escape and remained unchanged after escape. With respect to the agents used after
      escape, SASP and BC were substituted with other DMARDs. A combination with other
      DMARDs was usually administered to patients who had been receiving MTX. Taken
      together, the present results clarified the characteristics of DMARD escape and
      will contribute to the appropriate pharmacotherapy for RA.

PMID- 15738629
TI  - [Determination of magnesium stearate in pharmaceutical preparations using
      derivatization with 2-nitrophenylhydrazine and HPLC].
AB  - In general, spectrophotometric methods (inductively coupled plasma or atomic
      absorption spectrophotometry) are used for the assay of magnesium stearate (Mg
      St). In this study, a new rapid, selective assay method was developed for Mg-St
      in pharmaceutical formulations. The method was based on isocratic reverse-phase
      liquid chromatography using a mobile phase of acetonitrile-water (80:20, v/v)
      after precolumn derivatization with 2-nitrophenyl hydrazine for sensitive UV
      detection. Margaric acid was used as an internal standard and the substances were
      detectable at 230 nm or 400 nm. Using a short (2 cm) HPLC column reduced the
      analytical time to 5 min. Validation of the newly developed method was performed
      in accordance with the International Conference on Harmonization guidelines. The
      linearity range for Mg-St was 0.00-0.04 mg/ml (as the concentration of injected
      sample solution) and their correlation factor was 0.9998. The determination and
      detection limits for Mg-St were 6 microg and 2 microg, respectively. The proposed
      method was successfully applied to the determination of trace amounts of Mg-St in
      commercially available tablets with a high recovery percentage, good accuracy,
      and precision.

PMID- 15738630
TI  - Impairment state of cognitive performance and the affecting factors in
      outpatients following gastrointestinal endoscopy after single-dose diazepam.
AB  - Diazepam is commonly used as premedicant for endoscopic procedures. Wide
      interindividual differences have been observed in the residual cognitive effects
      of the drug after gastrointestinal endoscopy. Our aim was to clarify the major
      factors, including pharmacokinetic factors, contributing to this wide variation
      in residual cognitive effect after gastrointestinal endoscopy in the study. Sixty
      one outpatients undergoing gastrointestinal endoscopy participated in the study.
      Cognitive effects were evaluated in the diazepam group (n=52) by the digit symbol
      substitution test (DSST) twice before and 30 min after an intravenous
      administration of 5 mg diazepam; in the intervening time gastrointestinal
      endoscopy was performed. Plasma concentrations of diazepam were determined by
      HPLC. The control group (n=9) was tested by DSST in the same manner. The
      cognitive effects according to the change in DSST score was significantly decline
      in the diazepam group compared with the control group (by 0.2 versus -4.6;
      P=0.014). This prospective study confirmed that cognition was significantly
      impaired after gastrointestinal endoscopy by premedication to subjects with 5 mg
      diazepam. There were very wide variations in change in DSST score. However we
      could not identify the independent variables that best predicted DSST score
      difference in a multiple regression analysis for age, plasma albumin level, and
      plasma diazepam concentration 30 min after intravenous administration. We should
      pay attention to patients' individual states in cognitive performance following
      gastrointestinal endoscopy after single-dose diazepam.

PMID- 15738632
TI  - [Estimation of detection limit from slope of B/B0 in competitive ELISA].
AB  - A method has been proposed for determining the detection limit (L(D)) from the
      slope of a semilogarithmic plot of a B/B(0) curve in competitive enzyme linked
      immunosorbent assay (ELISA). As an application, this paper describes a graphic
      determination of L(D) from analogue data in the literature. The L(D) obtained
      corresponds to the concentration at which the relative standard deviation of
      concentration estimates is 30%.

PMID- 15738631
TI  - [Xanthine oxidase inhibitory activity and hypouricemia effect of propolis in
      rats].
AB  - The xanthine oxidase (XOD) inhibitory activity of propolis from China and Brazil
      was measured. The propolis from both place were seen to have XOD inhibitory
      activity. However, a stronger tendency was shown in the propolis from China. The
      compounds in each the propolis were measured quantitatively. A great deal of
      chrysin, galangin, and caffeic acid phenetyl ester were found in the propolis
      from China, an abundance of p-coumaric acid and artepillin C in the propolis from
      Brazil. Therefore it was revealed that the propolis compounds are very different
      depending on their place of origin. The XOD inhibitory activity of these five
      compounds was measured. Caffeic acid phenetyl ester had the strongest activity,
      with chrysin and galangin next; p-coumaric acid and artepillin C showed weak XOD
      inhibitory activity. We evaluated the hypouricemic effect of propolis from China
      on hyperuricemia induced by the uricase inhibitor, oxonic acid (500 mg/kg p.o., 1
      h before the test drugs), and measured plasma uric acid values in rats. Oral
      propolis had a hypouricemic effect 2 h after its administration to oxonate
      pretreated rats. These results suggested that a continuous intake of propolis may
      be effective for the prevention and the treatment of gout and hyperuricemia.

PMID- 15738633
TI  - [Catfish (Silurus asotus) lectin enhances the cytotoxic effects of doxorubicin].
AB  - Rhamnose-binding lectins are widely found in fish eggs. However, their biologic
      effects on cultured cells are still unknown. Since catfish (Silurus asotus) egg
      lectin (SAL) bound to globotriaosylceramide (Gb3) expressed on the surface of
      cells, we analyzed the relationship between Gb3 expression and SAL binding in
      tumor cell lines using Raji, Daudi, ACHN, P388, and K562 cells. Gb3 was highly
      expressed on Raji cells but not on K562 cells. SAL bound abundantly to Raji cells
      but not to K562 cells, and SAL binding depended on the amount of Gb3 on the cell
      surface. SAL caused a reduction in cell size and increased annexin-V binding to
      and propidium iodide (PI) incorporation into Raji cells. Although this effect on
      Raji cells might represent damage at the late apoptosis or necrosis stage, SAL
      treated Raji cells remained alive. Thus SAL enhanced PI incorporation into Raji
      cells without induction of cell death. We examined whether the effects of
      chemotherapeutic agent(s) are influenced by SAL. SAL increased the incorporation
      of doxorubicin (Dox) into Raji cells and consequently enhanced the cytotoxic
      effects of Dox. These results indicate that SAL may induce cell permeability
      without cytotoxity.

PMID- 15738634
TI  - Decoding cis-regulatory systems in ascidians.
AB  - Ascidians, or sea squirts, are lower chordates, and share basic gene repertoires
      and many characteristics, both developmental and physiological, with vertebrates.
      Therefore, decoding cis-regulatory systems in ascidians will contribute toward
      elucidating the genetic regulatory systems underlying the developmental and
      physiological processes of vertebrates. cis-Regulatory DNAs can also be used for
      tissue-specific genetic manipulation, a powerful tool for studying ascidian
      development and physiology. Because the ascidian genome is compact compared with
      vertebrate genomes, both intergenic regions and introns are relatively small in
      ascidians. Short upstream intergenic regions contain a complete set of cis
      regulatory elements for spatially regulated expression of a majority of ascidian
      genes. These features of the ascidian genome are a great advantage in identifying
      cis-regulatory sequences and in analyzing their functions. Function of cis
      regulatory DNAs has been analyzed for a number of tissue-specific and
      developmentally regulated genes of ascidians by introducing promoter-reporter
      fusion constructs into ascidian embryos. The availability of the whole genome
      sequences of the two Ciona species, Ciona intestinalis and Ciona savignyi,
      facilitates comparative genomics approaches to identify cis-regulatory DNAs.
      Recent studies demonstrate that computational methods can help identify cis
      regulatory elements in the ascidian genome. This review presents a comprehensive
      list of ascidian genes whose cis-regulatory regions have been subjected to
      functional analysis, and highlights the recent advances in bioinformatics and
      comparative genomics approaches to cis-regulatory systems in ascidians.

PMID- 15738635
TI  - Phylogenetic relationships among major species of japanese coleoid cephalopods
      (Mollusca: Cephalopoda) using three mitochondrial DNA sequences.
AB  - Phylogenetic relationships among 36 species of major coleoid cephalopods from
      Japanese waters were studied using partial sequences of three mitochondrial
      genes, 16S rDNA, 12S rDNA, and cytochrome c oxidase subunit I gene. Octopoda and
      Decapoda were monophylic groups. Within Sepioidea, Sepiadariidae and Sepiolidae
      were not closely related to Sepiidae, but rather related to Teuthoidea. Sepiidae
      with a distinct calcareous shell formed a single cluster. Myopsida was closely
      related to Oegopsida. Within Octopoda, Opisthoteuthis depressa and Argonauta argo
      diverged earlier than Octopodiidae. The common octopuses in Japanese waters were
      separated into three clusters. The first cluster occupied a basal position, and
      includes large-sized octopuses, such as Enteroctopus dofleini and Octopus
      (Paroctopus) conispadiceus from the continental shelf and upper slope. The second
      cluster consisted of long-armed octopuses, such as O. ornatus, O. minor, and O.
      sasakii. The third cluster contained small- to medium-sized octopus, such as
      Amphioctopus fangsiao, A. areolatus, O. cyaneus, and O. vulgaris, in which
      several species possess ocelli on the web. The second cluster formed the sister
      group to the third cluster.

PMID- 15738636
TI  - Phylogeography of loaches of the genus lefua (balitoridae, cypriniformes)
      inferred from mitochondrial DNA sequences.
AB  - In order to elucidate phylogenetic relationships and intraspecific variations and
      to infer the evolutionary process of loaches of the genus Lefua, we analyzed
      nucleotide sequences of the mitochondrial D-loop region of 100 specimens obtained
      from 97 localities in Japan and Korea. The genus Lefua includes three described
      species, L. nikkonis, L. echigonia, and L. costata and an undescribed species,
      Lefua sp. Our results showed that each species of Lefua formed a monophyletic
      group, indicating clearly that Lefua species can be genetically distinguished
      from one another. Lefua nikkonis was the most closely related to L. costata,
      while L. sp. was the most closely related to L. echigonia. Specimens of L. sp.
      were grouped into two intraspecific populations and specimens of L. echigonia
      were grouped into six populations. These populations were well separated
      geographically from one another by mountain ranges and highlands. We estimated
      the evolutionary time for splitting of the species and intraspecific populations,
      and speculated on the evolutionary process of the genus Lefua. Species of Lefua
      are severely threatened. Fundamental genetic information is indispensable for
      conservation. We presented genetic background in order to protect these
      threatened loaches.

PMID- 15738637
TI  - Receptor-type protein tyrosine phosphatase epsilon (PTPepsilonM) is a negative
      regulator of insulin signaling in primary hepatocytes and liver.
AB  - Impaired insulin receptor (IR) signaling leads to insulin resistance and type 2
      diabetes mellitus. Several inhibitors of the IR tyrosine kinase activity have
      recently been described and associated with human insulin resistance. Among these
      negative regulators, protein tyrosine phosphatases (PTPs) are likely to play a
      pivotal role in IR signaling. Transgenic studies revealed that PTP1B and TCPTP
      are primary candidates but IR of these animals can be finally dephosphorylated,
      suggesting that other PTPs are also involved in the dephosphorylation of IR. In
      this study, we showed that receptor-type PTPepsilon (PTP epsilonM)
      dephosphorylated IR in rat primary hepatocytes and tyrosines 972, 1158, 1162 and
      1163 were primary targets of PTP epsilonM. Wild type as well as substrate
      trapping DA forms of PTPepsilonM suppressed phosphorylation of IR downstream
      enzymes such as Akt, extracellular regulated kinase (ERK) and glycogen synthase
      kinase 3 (GSK3). It was also demonstrated that PTPepsilonM suppressed insulin
      induced glycogen synthesis and inhibited insulin-induced suppression of
      phosphoenol pyruvate carboxykinase (PEPCK) expression in primary hepatocytes.
      Furthermore, adenovirally introduced PTPepsilonM also exhibited inhibitory
      activity against suppression of PEPCK expression in mouse liver. These results
      suggest that PTPepsilonM is a negative regulator of IR signaling and involved in
      insulin-induced glucose metabolism mainly through direct dephosphorylation and
      inactivation of IR in hepatocytes and liver.

PMID- 15738639
TI  - Release of ecdysteroid-phosphates from egg yolk granules and their
      dephosphorylation during early embryonic development in silkworm, Bombyx mori.
AB  - Newly laid eggs of many insect species store maternal ecdysteroids as
      physiologically inactive phosphoric esters. In the silkworm Bombyx mori, we
      previously reported the presence of a specific enzyme, called ecdysteroid
      phosphate phosphatase (EPPase), which catalyzes the dephosphorylation of
      ecdysteroid-phosphates to increase the amount of free ecdysteroids during early
      embryonic development. In this study, we demonstrated that (1) EPPase is found in
      the cytosol of yolk cells, (2) ecdysteroid-phosphates are localized in yolk
      granules, being bound to the yolk protein vitellin (Vn), and (3) Vn-bound
      ecdysteroid-phosphates are scarcely hydrolyzed by EPPase, although free
      ecdysteroid-phosphates are completely hydrolyzed by EPPase. Thus, we investigated
      the mechanism by which ecdysteroid-phosphates dissociate from the Vn-ecdysteroid
      phosphate complex, and indicated that the acidification of yolk granules causes
      the dissociation of ecdysteroid-phosphates from the Vn-ecdysteroid-phosphate
      complex and thereby ecdysteroid-phosphates are released from yolk granules into
      the cytosol. Indeed, the presence of vacuolar-type proton-translocating ATPase in
      the membrane fraction of yolk granules was also verified by Western blot
      analysis. Our experiments revealed that Vn functions as a reservoir of maternal
      ovarian ecdysteroid-phosphates as well as a nutritional source during embryonic
      development. This is the first report showing the biochemical mechanism by which
      maternal Vn-bound ecdysteroid-phosphates function during early embryonic
      development.

PMID- 15738638
TI  - Expression patterns of a twist-related gene in embryos of the spider Achaearanea
      tepidariorum reveal divergent aspects of mesoderm development in the fly and
      spider.
AB  - We cloned an Achaearanea tepidariorum (Chelicerata, Arachnida) gene related to
      Drosophila twist (twi), which encodes a basic helix-loop-helix transcription
      factor required to specify mesoderm fate in the Drosophila embryo. The cloned
      spider gene was designated At.twist (At.twi). We examined its expression by whole
      mount in situ hybridization. At.twi transcripts were first detected in cells
      located at the polar and equatorial areas of the spherical embryo when the
      cumulus reached the equator. As the extra-embryonic area expanded, more cells
      expressed At.twi transcripts. The At.twi-expressing cells became distributed
      nearly uniformly in the embryonic area. At these stages, some At.twi-expressing
      cells were found in the surface epithelial cell layer, but other At.twi
      expressing cells were at slightly deeper positions from the surface. When the
      embryo was transformed into a germ band, all At.twi-expressing cells were
      situated just beneath the surface ectoderm, where they became metamerically
      arranged. Although little expression was observed in the caudal lobe of the
      elongating germ band, new stripes of At.twi expression appeared beneath the
      ectoderm in accordance with the posterior growth. These observations suggested
      that the cells expressing At.twi were most likely mesoderm. We propose that
      At.twi can be used as a molecular marker for analyzing mesoderm development in
      the spider embryo. Moreover, comparison of the expression patterns of twi and
      At.twi revealed divergent aspects of mesoderm development in the fly and spider.
      In addition, we cloned an Achaearanea gene related to snail, which is another
      mesoderm-determining gene in Drosophila, and showed that its expression was
      restricted to the ectoderm with no indication for a role in mesoderm development.

PMID- 15738640
TI  - Immunocytochemical identification of neuroactive substances in the antennal lobe
      of the male silkworm moth Bombyx mori.
AB  - As a first step towards understanding the functional role of neuroactive
      substances in the first olfactory center of the male silkworm moth Bombyx mori,
      we carried out an immunocytochemical identification of antennal lobe neurons.
      Antibodies against gamma-aminobutyric acid (GABA), FMRFamide, serotonin, tyramine
      and histamine were applied to detect their existence in the antennal lobe. In the
      present immunocytochemical study, we clarified four antenno-cerebral tracts from
      their origin and projection pathways to the protocerebrum, and revealed the
      following immunoreactive cellular organization in the antennal lobe. 1) Local
      interneurons with cell bodies in the lateral cell cluster showed GABA, FMRFamide
      and tyramine immunoreactivity. 2) Projection neurons passing through the middle
      antenno-cerebral tract with cell bodies in the lateral cell cluster showed GABA
      and FMRFamide immunoreactivity. Projection neurons passing through the outer
      antenno-cerebral tract with cell bodies in the lateral cell cluster showed
      FMRFamide immunoreactivity. 3) Centrifugal neurons passing through the inner
      antenno-cerebral tract b with cell bodies located outside the antennal lobe
      showed serotonin and tyramine immunoreactivity. Our results revealed basic
      distribution patterns of neuroactive substances in the antennal lobe and
      indicated that each projection pathway from the antennal lobe to the
      protocerebrum contains specific combination of neuroactive substances.

PMID- 15738641
TI  - Establishment of a sandwich ELISA system to detect diapause hormone, and
      developmental profile of hormone levels in egg and subesophageal ganglion of the
      silkworm, Bombyx mori.
AB  - In the silkworm Bombyx mori, diapause hormone (DH) is produced in the female
      subesophageal ganglion (SG) and induces embryonic diapause by targeting
      developing ovaries. DH is processed from a precursor protein consisting of DH,
      pheromone biosynthesis activating neuropeptide (PBAN) and three other
      neuropeptides (SGNPs). Because these five neuropeptides share a common sequence,
      FXPRLamide, at the C-terminus, a direct and specific assay for DH itself is
      required in order to understand the profile of concentration changes. In this
      study, we produced a mouse monoclonal antibody (anti-DH[N] mAb) against the N
      terminal region of DH and developed a sandwich enzyme-linked immunosorbent assay
      using the anti-DH[N] mAb and a rabbit polyclonal antibody against the C-terminus
      of DH. This procedure enabled us to specifically quantify the DH molecule at
      femtomolar levels (equivalent to 1/10 of SG). We then plotted DH levels in eggs
      and SGs during embryonic and post-embryonic development. DH was present in late
      stage embryos that had been destined for the production of both diapause and
      nondiapause eggs. DH levels in SG gradually increased in both types during larval
      development and peaked at the early pupal stage. At the middle pupal stage, DH
      levels in SG and SG-brain complex decreased markedly in the diapause-egg
      producing type, thus indicating active release of DH into the hemolymph. From 5th
      instar larva to adult, no sexual differences in DH levels were observed in SGs or
      SG-brain complexes from diapause and nondiapause egg-producing types.

PMID- 15738642
TI  - Additivity in murine circadian phototransduction.
AB  - Additivity in the circadian phototransduction system of the mouse has not been
      tested directly. Because of this, accurate prediction of circadian phase shifts
      elicited by polychromatic light stimuli cannot be derived from the results of
      studies using monochromatic light stimuli. This limitation also makes it
      impossible to deduce the relative contributions of the photoreceptive mechanisms
      (rods, cones and melanopsin-containing retinal ganglion cells) underlying
      circadian phototransduction in the mouse. Using nearly monochromatic light
      stimuli of different spectral composition, and combinations thereof, we
      demonstrated that murine circadian phototransduction exhibits additivity. Based
      on the locomotor activity phase shifts elicited by these stimuli, we developed
      the first quantitative assessment of the relative contributions of conventional
      and novel photoreceptive mechanisms for circadian functioning in the mouse.

PMID- 15738643
TI  - Long term adrenal insufficiency induces skeletal muscle atrophy and increases the
      serum levels of active form myostatin in rat serum.
AB  - Skeletal muscle wasting is a common symptom in the adrenal insufficiency such as
      Addison's disease. Although it has been suspected that several cytokines and/or
      growth factors are responsible for the manifestation of the symptom, the precise
      mechanisms underlying the phenomenon have so far been poorly understood.
      Myostatin is predominantly expressed in skeletal muscles and involved in the
      regulation of skeletal muscle mass. Recently, several reports indicated that
      myostatin is secreted into the circulation and the increased levels of
      circulating myostatin is associated with the induction of skeletal muscle wasting
      in adult animals. We, therefore, hypothesized that the increased levels of
      circulating myostatin may account for the development of skeletal muscle wasting
      in adrenal insufficiency. To test the validity of this hypothesis, we compared
      the serum levels of myostatin in normal with those in bilaterally
      adrenalectomized (ADX) rats, a model of Addison's disease, by Western blot
      analysis. The active form of myostatin (13 kDa) was barely detectable in the sera
      collected either 1 month or 2 month after adrenalectomy, but present at
      conspicuously detectable levels in those obtained 3 month after the operation,
      while the total amounts of myostatin proteins (sum of the precursor and the
      active forms) remained constant at all the time points examined post-operatively.
      These results are consistent with the hypothesis that the increased serum levels
      of active form of myostatin protein, induced yet unknown post-translational
      control mechanisms may be responsible, at least in part, for the muscle wasting
      associated with the adrenal insufficiency syndromes.

PMID- 15738644
TI  - Changes in the distribution of tenascin and fibronectin in the mouse ovary during
      folliculogenesis, atresia, corpus luteum formation and luteolysis.
AB  - Tenascin and fibronectin are components of the extracellular matrices that oppose
      and promote adhesion, respectively. Using immunohistochemical techniques, we
      studied the distribution of tenascin and fibronectin in the mouse ovary, in which
      dynamic reconstruction and degeneration occur during folliculogenesis, atresia,
      ovulation, corpus luteum formation and luteolysis. In growing follicles, tenascin
      was only detected in the theca externa layer, while fibronectin was detected in
      the theca externa layer, theca interna layer and basement membrane. During
      follicular atresia, granulosa cells, which are surrounded by the basement
      membrane, began to die through apoptosis. In atretic follicles, tenascin was
      detected in the basement membrane and theca externa layer. Distribution of
      fibronectin in atretic follicles was similar to that in healthy growing
      follicles, except that granulosa cells were slightly immunopositive for
      fibronectin. In young corpus luteum, luteal cells exhibit high 3 beta 
      hydroxysteroid dehydrogenase (3 beta -HSD) activity, an enzyme indispensable for
      progesterone production. Tenascin was barely detected in young luteal cells. 3
      beta -HSD activity in luteal cells declines with corpus luteum age, and in older
      corpus luteum there is an increase in apoptotic death of luteal cells. Tenascin
      was intensely immunopositive in old luteal cells.In contrast, fibronectin
      immunostaining in luteal cells was relatively constant during corpus luteum
      formation and luteolysis. Our observations suggest that tenascin is critical in
      controlling the degenerative changes of tissues in mouse ovaries. Moreover, in
      all circumstances observed in this study, tenascin always co-localized with
      fibronectin, suggesting fibronectin is indispensable for the function of
      tenascin.

PMID- 15738645
TI  - Reproduction of Zoanthus sansibaricus in the infra-littoral zone at Taisho Lava
      Field, Sakurajima, Kagoshima, Japan.
AB  - In order to obtain data on the reproductive pattern of the clonal cnidarian
      Zoanthus sansibaricus, polyps were sampled by scuba gear at Taisho Lava Field,
      Sakurajima, for 24 months between April 2000 and March 2002 (polyps collected
      weekly for breeding season). According to cross-sections, Zoanthus polyps were
      divided into three sexual types; male, female and asexual, and were found in the
      same colony. At Sakurajima, Zoanthus sansibaricus spawned in the middle of July,
      releasing oocytes and sperm. These spawning events occur synchronously with moon
      phase. In gametogenesis of Zoanthus sansibaricus, oocytes became recognizable in
      February and grew rapidly from the end of June onward. Spermatocytes became
      recognizable in June and matured rapidly in the middle of July. After spawning
      events, oocytes still remaining in the endoderm were absorbed into Zoanthus
      tissue quickly.

PMID- 15738646
TI  - Study on the genus Euops Schoenherr (Coleoptera: attelabidae) from China, with
      descriptions of a new subgenus and six new species.
AB  - The present paper deals with 19 species in four subgenera of the attelabid genus
      Euops from China (including Taiwan), of which six species and a subgenus are new
      to science. The subgenus Synaptops is newly divided into three species-groups. A
      key to species, with photographs and line illustrations of important features of
      new species is provided.

PMID- 15738647
TI  - Multidrug resistance in photodynamic therapy.

PMID- 15738648
TI  - Molecular and phenotypic heterogeneity of metastatic prostate cancer.
AB  - Metastatic prostate cancer remains a prevalent disease in the United States that
      requires detailed characterization of its pathobiology. In the December 2004
      issue of Cancer Research, a comprehensive study by Shah et al. demonstrated that
      metastatic androgen-independent prostate cancer is a collective group of diseases
      even within the same patient. Understanding the molecular and phenotypic
      determinants of this heterogeneity is essential in assessing therapeutic outcomes
      in the management of prostate cancer progression.

PMID- 15738649
TI  - A mouse model of activating Met mutations.
AB  - Tyrosine kinase-activating mutations in Met have been observed in hereditary
      papillary renal carcinomas (HPRC) and their transforming potential has been
      examined both in vitro and in tumor xenografts. To study the influence of these
      mutations in the mouse germline, we generated mice with targeted mutations in the
      murine met locus. Five mouse lines with mutant Met were created: WT, D1226N,
      Y1228C, M1248T, and M1248T/L1193V. Unexpectedly, the different mutant Met lines
      developed unique tumor profiles including carcinomas, sarcomas, and lymphomas.
      More surprising was that we observed non-random duplication of the mutant met
      allele in a majority of tumors from the mutant mouse lines. This selective
      chromosomal amplification has been observed in patients with HPRC. This study
      illustrates the importance of activating Met mutations in tumorigenesis and
      indicates that mutations within the kinase domain distinctly affect downstream
      signaling. Our Met mutant mice will provide a valuable model for testing Met
      inhibitors on tumors containing activating mutations present in human cancers and
      for understanding the molecular events critical for Met-mediated tumorigenesis.

PMID- 15738651
TI  - Cell cycle progression without cyclin D-CDK4 and cyclin D-CDK6 complexes.
AB  - D-type cyclins (cyclin D1, D2 and D3) and their associated cyclin-dependent
      kinases CDK4 and CDK6 were thought to represent important, perhaps essential
      components of the core cell cycle apparatus. However, recent analyses of mice
      lacking D-cyclins, or CDK4 and CDK6 reveal that these proteins are critically
      required for proliferation only in the selected cell types. Intriguingly, several
      compartments can develop in the absence of cyclin D-CDK4/6 activity, revealing
      that these cells can proliferate in a cyclin D-independent fashion.

PMID- 15738652
TI  - Histone deacetylase inhibitors in programmed cell death and cancer therapy.
AB  - Histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid
      (SAHA), are targeted anticancer agents that have significant anticancer activity
      at doses well tolerated by patients. Recently, we found that HDAC inhibitors can
      trigger both mitochondria-mediated apoptosis and caspase-independent autophagic
      cell death, indicating potential benefit of HDAC inhibitors in treating cancers
      with apoptotic defects. We also found that thioredoxin (TRX) might play a
      significant role in HDAC inhibitor-induced cell death, and HDAC inhibitors
      increase TRX levels in normal cells but not transformed cells, which is likely to
      be one of the reasons why HDAC inhibitors preferentially kill cancer cells. In
      this review, we discuss the study of HDAC inhibitors in cell death and cancer
      research, the implications of our recent findings, and some outstanding questions
      that need to be addressed.

PMID- 15738650
TI  - HuntING4 new tumor suppressors.
AB  - The well-characterized function of many tumor suppressors is to directly regulate
      cell cycle events. We recently reported a genetic screen to identify genes that
      suppress loss of contact inhibition but do not inhibit normal cell proliferation.
      ING4, one of the genes identified by the screen, is frequently mutated in human
      cancer, suggesting a role for ING4 as a tumor suppressor. ING4 suppresses tumor
      cell features such as loss of contact inhibition, cell growth in soft agar, and
      tumor growth in nude mice. ING4 may belong to a class of tumor suppressors whose
      function is specific to a tumorigenic event that does not directly involve
      deregulation of the cell cycle. Studies of these tumor suppressors may provide
      insight into the molecular mechanisms underlying such tumorigenic events.

PMID- 15738653
TI  - The double life of the Ku protein: facing the DNA breaks and the extracellular
      environment.
AB  - The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double strand break
      recognition and repair. It has been shown, more than ten years ago, that Ku is
      also expressed at the cell surface of different cells types along with its
      intracellular pool within the nucleus and the cytoplasm but involvement of Ku in
      cell-cell and cell-extracellular matrix adhesion has been only recently
      demonstrated. In addition, we have shown that Ku may have a second and unexpected
      activity in cell/microenvironment interaction. Indeed, Ku appears to be involved
      in extracellular proteolytic processes through its specific interaction, on the
      cell surface, with the matrix metalloprotease 9. Taken together, these results
      suggest that Ku function at the cell surface is likely to be important in tumour
      invasion. Various fundamental questions arise from these observations. How Ku is
      expressed on the cell surface, why a protein with completely unrelated functions
      also serve as an integrin-like molecule once expressed at the cell surface and is
      this functional moonlighting of Ku related to cell transformation remain open
      issues that will be discussed here.

PMID- 15738654
TI  - Modulation of the ARF-p53 pathway by the small DNA tumor viruses.
AB  - The small DNA tumor viruses encode proteins that subvert many of the pivotal
      growth regulatory pathways within the cell to facilitate their own replication.
      The cell responds to viral infection/proteins by activating the p53 tumor
      suppressor pathway. Activation of p53 could impair a productive viral infection
      at many levels, including the inhibition of viral DNA replication and/or the
      premature death of infected cells. Therefore, DNA viruses encode proteins that
      inactivate the p53 tumor suppressor pathway. Understanding how DNA viral proteins
      activate/inactivate the p53 pathway has provided invaluable insights into
      tumorigenesis. Recent studies with polyoma virus have identified a viral protein
      (PyST) that inhibits ARF-mediated activation of p53, and revealed a novel role
      for PP2A in the regulation of the ARF-p53 tumor suppressor pathway.

PMID- 15738655
TI  - The PPAR-gamma agonist pioglitazone post-transcriptionally induces p21 in PC3
      prostate cancer but not in other cell lines.
AB  - The anti-diabetic thiozolidinedione compound pioglitazone, a peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) agonist, has been found to
      have growth inhibitory effects in some cancer cells. The mechanism underlying
      this growth suppression is not well understood. In this study, we evaluated the
      effect of pioglitazone on p53 and p21 expression in various cancer cell lines
      with different p53 status. The cells with wild type p53 did not show any change
      in p53 levels in response to pioglitazone. Also, none of the cell lines exhibited
      p53-dependent or independent transcriptional induction of p21(WAF1/CIP1) by
      pioglitazone. However, PC3, an androgen-insensitive prostate cancer cell line
      with deletion of p53 showed an appreciable post-transcriptional induction of p21
      expression after treatment with pioglitazone. These results imply that
      pioglitazone generally does not modulate p21 transcription in human cancer cell
      lines.

PMID- 15738656
TI  - A cell-based screening strategy that predicts mutations in oncogenic tyrosine
      kinases: implications for clinical resistance in targeted cancer treatment.
AB  - The discovery of tyrosine kinases that, once deregulated, can cause malignancy,
      allowed the development of specifically acting anti-cancer compounds. In chronic
      myeloid leukaemia (CML), the Bcr-Abl kinase inhibitor imatinib (STI571, Gleevec)
      induces impressive response rates. However, resistance occurs especially in
      advanced phase CML and Ph+ ALL, primarily as a consequence of point mutations
      within the Bcr-Abl kinase domain that prevent imatinib from binding. To overcome
      imatinib resistance, alternative Abl kinase inhibitors are finding their way into
      clinical trials. However, it is likely that resistance to second-generation
      compounds will occur as well. Therefore, it will be critical to determine
      specific resistance profiles for each particular compound. We recently developed
      a cell-based screening strategy that allows one to predict the pattern and
      relative abundance of Bcr-Abl resistance mutations emerging in the presence of
      imatinib or an alternative Abl-kinase inhibitor. Using this strategy, the
      findings in inhibitor resistant sublines reflect observations made in CML
      patients with imatinib resistance, including Bcr-Abl mutations, amplification of
      the Bcr-Abl gene, and overexpression of the Bcr-Abl protein. We here provide a
      detailed methodological description, and discuss the implications of this
      strategy for different clinically relevant oncogenic tyrosine kinases.

PMID- 15738657
TI  - Mediation of biomaterial-cell interactions by adsorbed proteins: a review.
AB  - An appropriate cellular response to implanted surfaces is essential for tissue
      regeneration and integration. It is well described that implanted materials are
      immediately coated with proteins from blood and interstitial fluids, and it is
      through this adsorbed layer that cells sense foreign surfaces. Hence, it is the
      adsorbed proteins, rather than the surface itself, to which cells initially
      respond. Diverse studies using a range of materials have demonstrated the pivotal
      role of extracellular adhesion proteins--fibronectin and vitronectin in
      particular--in cell adhesion, morphology, and migration. These events underlie
      the subsequent responses required for tissue repair, with the nature of cell
      surface interactions contributing to survival, growth, and differentiation. The
      pattern in which adhesion proteins and other bioactive molecules adsorb thus
      elicits cellular reactions specific to the underlying physicochemical properties
      of the material. Accordingly, in vitro studies generally demonstrate favorable
      cell responses to charged, hydrophilic surfaces, corresponding to superior
      adsorption and bioactivity of adhesion proteins. This review illustrates the
      mediation of cell responses to biomaterials by adsorbed proteins, in the context
      of osteoblasts and selected materials used in orthopedic implants and bone tissue
      engineering. It is recognized, however, that the periimplant environment in vivo
      will differ substantially from the cell-biomaterial interface in vitro. Hence,
      one of the key issues yet to be resolved is that of the interface composition
      actually encountered by osteoblasts within the sequence of inflammation and bone
      regeneration.

PMID- 15738658
TI  - Integrin expression and osteopontin regulation in human fetal osteoblastic cells
      mediated by substratum surface characteristics.
AB  - Integrin-mediated adhesion of anchorage-dependent cells to scaffolds is a
      critical component of tissue engineering. We investigated integrin expression by
      the human fetal osteoblastic cell line, hFOB 1.19 (hFOB), as a function of
      substratum surface wettability. The influence of surface wettability on bone cell
      phenotype was also examined. Plasma-treated quartz (PTQ) and glass (PTG)
      (hydrophilic, contact angles of 0 degrees), octadecyltrichlorosilane-treated
      quartz (STQ) and glass (STG) (hydrophobic, contact angles above about 100
      degrees), and tissue culture polystyrene were used for cell culture. hFOB cells
      cultured on hydrophilic substrata displayed well-developed actin stress fibers
      relative to cells on hydrophobic substrata. Western blot analysis revealed that
      hFOB cells cultured on hydrophobic substrata (STQ or STG) express lower levels of
      alphav and beta3 integrin subunits than do cells on hydrophilic substrata (PTQ or
      PTG). This effect was more pronounced in cells on STQ than on STG. These
      variations in integrin expression were lessened by extended culture time. Double-
      labeled integrin/actin immunofluorescence confirmed Western blot results, that
      is, cells cultured on PTQ displayed distinct, large plaques of alphav and beta3
      subunits and integrin alphavbeta3, as well as their colocalization with actin
      stress fiber ends, whereas cells on STQ did not display integrin plaques after 24
      h and displayed only minimal plaque formation after 3 days. Vinculin, a focal
      adhesion protein that mediates binding between the integrin and actin
      cytoskeleton, appeared in Western blots to mimic the variations of alphav and
      beta3 expression with respect to surface wettability. Interestingly, real-time RT
      PCR analysis showed that hFOB cultured on hydrophobic substrata, which have
      downregulated alphav and beta3 integrin subunits, displayed greater steady state
      mRNA levels of osteopontin, an extracellular matrix (ECM) protein containing the
      Arg-Gly-Asp (RGD) integrin recognition sequence, than did cells cultured on
      hydrophilic substrata. Our results imply that substratum surface wettability
      regulates integrin-mediated bone cell adhesion and further influences the
      expression of bone cell-ECM complexes.

PMID- 15738659
TI  - Thermoresponsive terpolymeric films applicable for osteoblastic cell growth and
      noninvasive cell sheet harvesting.
AB  - A novel multifunctional linear block copolymer, poly(N-isopropylacrylamide-co
      acrylic acid)-b-poly( L-lactic acid) (NAL), was synthesized to expand the concept
      of cell sheet engineering by using its thermoresponsive property and
      processibility. The chemical structure of synthesized NAL was confirmed by
      Fourier transform infrared spectroscopy, and its molar mass (103,500 g.mol(-1))
      and molar mass distribution were determined by matrix-assisted laser
      desorption/ionization-time of flight mass spectroscopy. NAL copolymer was
      fabricated into thin films by spin-casting. Spin-cast NAL films displayed
      thermoresponsive properties as demonstrated by surface wettability and topology
      changes from relatively more hydrophobic (contact angle of 56 degrees) and
      rougher at 37 degrees C to relatively more hydrophilic (contact angle of 40
      degrees) and smoother at 22 degrees C, as assessed by contact angle measurement
      and atomic force microscopy, respectively. Murine osteoblastic MC3T3-E1 cells
      displayed comparable adhesion but slower proliferation on NAL films than on
      poly(L-lactic acid) (PLLA) films and tissue culture polystyrene (TCPS). Within 9
      days of cell culture, the highest alkaline phosphatase activity of MC3T3-E1 cells
      occurred later (on day 9) on NAL films than on PLLA films and TCPS (on day 6). A
      well-established MC3T3-E1 cell sheet was successfully detached from NAL films, in
      the absence of enzymes, within about 5 min by simply lowering the temperature
      from 37 degrees C to room temperature. NAL copolymer has potential for use in the
      controlled release of therapeutic agents while simultaneously supporting cell
      growth. In addition, it may be applicable for noninvasive two- or three
      dimensional cell sheet harvesting.

PMID- 15738660
TI  - Modulation of proliferation and differentiation of human bone marrow stromal
      cells by fibroblast growth factor 2: potential implications for tissue
      engineering of tendons and ligaments.
AB  - Bone marrow stromal cells (BMSCs) play a central role in the repair and
      regeneration of mesenchymal tissues. For tissue engineering of ligaments and
      tendons, both stimulation of cell proliferation and differentiation with
      increased expression of essential extracellular matrix proteins and cytoskeletal
      elements are desirable. This study analyzes the effect of low-dose (3 ng/mL)
      fibroblast growth factor 2 (FGF-2) and high-dose FGF-2 (30 ng/mL) on
      proliferation (bromodeoxyuridine content, spectrophotometry), differentiation
      (transcription of collagen I, collagen III, fibronectin, elastin, alpha-smooth
      muscle actin, and vimentin, reverse transcription-polymerase chain reaction, and
      cell density and apoptosis (annexin V, fluorescence-activated cell sorting) of
      human BMSCs, and compares the results with those of a control group without FGF
      2. Low-dose FGF-2 triggered a biphasic BMSC response: on day 7, cell
      proliferation reached its maximum and was significantly higher compared with the
      other groups. On days 14 or 28, collagen I, collagen III, fibronectin, and alpha-
      smooth muscle actin mRNA expression was significantly enhanced in the presence of
      low-dose FGF-2. In contrast, high-dose FGF-2 did not stimulate differentiation or
      proliferation. Vimentin mRNA was expressed only in cultures with low-dose and
      high-dose FGF-2 after 14 and 28 days. Cell density was significantly higher in
      cultures with low-dose FGF-2 compared with the group with high-dose FGF-2 on days
      7, 14, and 28. The apoptosis rate remained stable, at a rather high level, in all
      groups. Microscopic investigation of the cell cultures with low-dose FGF-2 showed
      more homogeneous, dense, fibroblast-like, spindle-shaped cells with long cell
      processes compared with cultures with high-dose, or no FGF-2. Low-dose FGF-2 may
      be useful for tissue engineering of ligaments and tendons by increasing BMSC
      proliferation and stimulating mRNA expression of specific extracellular matrix
      proteins and cytoskeletal elements.

PMID- 15738661
TI  - Evaluation of an in vitro model of hepatic inflammatory response by gene
      expression profiling.
AB  - The body's response to biochemical stress involves coordinated changes in the
      expression of several sets of genes that regulate its return to homeostasis.
      Although several cell culture systems have been utilized for studying such
      complex physiological events in vitro, their assessment has been limited to
      biochemical assays on individual genes and proteins, limiting interpretation of
      the results in a systems context. Advances in genomics provide an opportunity to
      provide a more comprehensive assessment. In this study, we have used DNA
      microarrays to profile gene expression dynamics during interleukin 6-stimulated
      inflammation in hepatocytes maintained in a stable, collagen double-gel in vitro
      model system. The observed expression profile was also compared with that
      obtained from rat liver tissue after burn injury to determine the extent and
      nature of responses captured by the in vitro system. Our results indicate that
      several aspects of the in vivo hepatic inflammatory response can be captured by
      the in vitro system at the molecular systems level. Statistical analysis of the
      mRNA profiles was also used to characterize the temporal response in each model
      system and demonstrate similar behavior. A small panel of molecules involved in
      the hepatic acute-phase response was also profiled, using quantitative kinetic
      polymerase chain reaction, to confirm these observations. These results indicate
      the utility of the stable hepatocyte culture system for expression profiling of
      inflammatory states and for providing insights into the interplay of changes in
      gene expression during complex physiological states.

PMID- 15738662
TI  - In vitro expansion of human nasoseptal chondrocytes reveals distinct expression
      profiles of G1 cell cycle inhibitors for replicative, quiescent, and senescent
      culture stages.
AB  - In vitro expansion of chondrocytes for tissue-engineering applications is limited
      by forms of growth arrest known as quiescence and replicative senescence. At the
      molecular level cyclin-dependent kinase inhibitors (CDKIs) are involved in
      mediating growth arrest in the G1 phase of the cell cycle. Using ribonuclease
      protection assays and immunocytochemical staining methods, we quantitatively
      analyzed expression profiles of G1 cell cycle inhibitors at the mRNA and protein
      levels. These inhibitors included the CDKIs of the CIP/KIP family (p21CIP1
      p27KIP1, and p57KIP2) and the INK4 family (p15INK4b, p16INK4a, p18INK4c, and
      p19INK4d) as well as the retinoblastoma protein-family (pRb, p107, and p130) and
      the tumor suppressor p53. Analysis was carried out in proliferating, quiescent,
      and senescent states of primary cultures of adult human nasoseptal chondrocytes.
      The most pronounced effect (p < 0.0001) between cultures in proliferation and
      cultures in growth arrest was an increased expression of the CDKIs p57KIP2 and
      p15INK4b for quiescent growth arrest, and of p16INK4a, p15INK4b, and p57KIP2 for
      senescent growth arrest. Thus, these cell cycle inhibitors represent potential
      candidates for selective intervention to promote cellular multiplication of
      chondrocytes undergoing in vitro expansion for tissue-engineering applications.
      Possible methods of modulation include the targeted elimination of specifically
      identified cell cycle inhibitors by antisense technologies.

PMID- 15738664
TI  - Tissue reorganization in response to mechanical load increases functionality.
AB  - In the rapidly growing field of tissue engineering, the functional properties of
      tissue substitutes are recognized as being of the utmost importance. The present
      study was designed to evaluate the effects of static mechanical forces on the
      functionality of the produced tissue constructs. Living tissue sheets
      reconstructed by the self-assembly approach from human cells, without the
      addition of synthetic material or extracellular matrix (ECM), were subjected to
      mechanical load to induce cell and ECM alignment. In addition, the effects of
      alignment on the function of substitutes reconstructed from these living tissue
      sheets were evaluated. Our results show that tissue constructs made from living
      tissue sheets, in which fibroblasts and ECM were aligned, presented higher
      mechanical resistance. This was assessed by the modulus of elasticity and
      ultimate strength as compared with tissue constructs in which components were
      randomly oriented. Moreover, tissue-engineered vascular media made from a
      prealigned living tissue sheet, produced with smooth muscle cells, possessed
      greater contractile capacity compared with those produced from living tissue
      sheets that were not prealigned. These results show that the mechanical force
      generated by cells during tissue organization is an asset for tissue component
      alignment. Therefore, this work demonstrates a means to improve the functionality
      (mechanical and vasocontractile properties) of tissues reconstructed by tissue
      engineering by taking advantage of the biomechanical forces generated by cells
      under static strain.

PMID- 15738665
TI  - Potential of nanofiber matrix as tissue-engineering scaffolds.
AB  - Tissue-engineering scaffolds should be analogous to native extracellular matrix
      (ECM) in terms of both chemical composition and physical structure. Polymeric
      nanofiber matrix is similar, with its nanoscaled nonwoven fibrous ECM proteins,
      and thus is a candidate ECM-mimetic material. Techniques such as electrospinning
      to produce polymeric nanofibers have stimulated researchers to explore the
      application of nanofiber matrix as a tissue-engineering scaffold. This review
      covers the preparation and modification of polymeric nanofiber matrix in the
      development of future tissue-engineering scaffolds. Major emphasis is also given
      to the development and applications of aligned, core shell-structured, or surface
      functionalized polymer nanofibers. The potential application of polymer
      nanofibers extends far beyond tissue engineering. Owing to their high surface
      area, functionalized polymer nanofibers will find broad applications as drug
      delivery carriers, biosensors, and molecular filtration membranes in future.

PMID- 15738663
TI  - Perlecan domain I promotes fibroblast growth factor 2 delivery in collagen I
      fibril scaffolds.
AB  - Perlecan, a heparan sulfate proteoglycan, is widely distributed in developing and
      adult tissues and plays multiple, important physiological roles. Studies with
      knockout mouse models indicate that expression of perlecan and heparan sulfate is
      critical for proper skeletal morphogenesis. Heparan sulfate chains bind and
      potentiate the activities of various growth factors such as fibroblast growth
      factor 2 (FGF-2). Previous studies indicate that important biological activities
      are associated with the heparan sulfate-bearing domain I of perlecan (PlnDI;
      French et al. J. Bone Miner. Res. 17 , 48, 2002). In the present study, we have
      used recombinant, glycosaminoglycan-bearing PlnDI to reconstitute three
      dimensional scaffolds of collagen I. Collagen I fibrils bound PlnDI much better
      than native collagen I monomers or heat-denatured collagen I preparations.
      Heparitinase digestion demonstrated that recombinant PlnDI was substituted with
      heparan sulfate and that these heparan sulfate chains were critically important
      not only for efficient integration of PlnDI into scaffolds, but also for FGF-2
      binding and retention. PlnDI-containing collagen I scaffolds to which FGF-2 was
      bound sustained growth of both MG63, an osteoblastic cell line, and human bone
      marrow stromal cells (hBMSCs) significantly better than scaffolds lacking either
      PlnDI or FGF-2. Collectively, these studies demonstrate the utility of PlnDI in
      creating scaffolds that better mimic natural extracellular matrices and better
      support key biological activities.

PMID- 15738666
TI  - Engrafted bone marrow-derived flk-(1+) mesenchymal stem cells regenerate skin
      tissue.
AB  - Stem cell plasticity has created great interest because of its potential
      therapeutic application in degenerative or inherited diseases. Transplantation of
      bone marrow-derived stem cells was shown to give rise to cells of muscle, liver,
      nerve, endothelium, epithelium, and so on. But there are still disputes about
      stem cell plasticity, especially concerning the contribution of bone marrow
      derived cells to skin cells. In this study, CM-DiI fluorescence-labeled Flk-(1+)
      bone marrow mesenchymal stem cells (bMSCs) of BALB/c mice (H-2Kd, white) were
      transplanted into lethally irradiated C57BL/6 mice (H-2Kb, black). By
      fluorescence tracing, we found that donor cells could migrate and take residency
      at the skin, which was confirmed by Y chromosome-specific PCR and Southern blot.
      The recipient mice grew white hairs about 40 days later and white hairs could
      spread over the body. Immunochemistry staining and RT-PCR demonstrated that skin
      tissue within the white hair regions was largely composed of donor-derived H-2Kd
      cells, including stem cells and committed cells. Furthermore, most skin cells
      cultured from white hair skin originated from the donor. Thus, our findings
      provide direct evidence that bone marrow-derived cells can give rise to
      functional skin cells and regenerate skin tissue. These may have important
      scientific implications in stem cell biology and transplantation therapy for skin
      tissue injury.

PMID- 15738667
TI  - Healing of critically sized femoral defects, using genetically modified
      mesenchymal stem cells from human adipose tissue.
AB  - The FDA has approved the clinical use of recombinant bone morphogenetic proteins
      (BMPs). However, the use of recombinant BMPs in humans has required large doses
      of the proteins to be effective, which suggests that the delivery method of bone
      morphogenetic proteins needs to be optimized. Gene therapy is an alternative
      method to deliver such recombinant proteins, and gene transfer techniques have
      been tested on a variety of cell types including bone marrow cells, skin
      fibroblasts, peripheral blood monocytes, and muscle-derived cells. In this study,
      we sought to determine the ability of BMP-2-producing human adipose-derived
      mesenchymal stem cells to heal a critically sized femoral defect in a nude rat
      model. After approval by the human subjects protection committee, human adipose
      tissue was obtained from healthy donors. The lipoaspirate was processed as
      previously described (De Ugarte, D.A., et al. Cells Tissues Organs 174, 101,
      2003). Cells were grown in culture and infected with a BMP-2-carrying adenovirus.
      Five million cells were applied to a collagen- ceramic carrier and implanted into
      femoral defects as previously described (Zuk, P.A., et al. Mol. Biol. 13, 4279,
      2002). All animals were killed at 8 weeks. Femora were dissected out and
      underwent radiographic, histologic, and biomechanical analysis. Eleven of the 12
      femora in the group treated with human processed lipoaspirate (HPLA) cells
      genetically modified to overexpress BMP-2 had healed at 8 weeks. This was
      assessed by radiographs, by mechanical testing, and by histology. The one femur
      that did not heal had a subacute infection. All eight of the femora treated with
      the rhBMP-2-impregnated collagen-ceramic carrier healed. No statistically
      significant difference was detected between these two groups. Evaluation of the
      control groups: group II (collagen- ceramic carrier with HPLA cells) and group
      III (collagen-ceramic carrier alone) showed that none of the femora had healed by
      8 weeks. Our results indicate that HPLA cells genetically modified by adenoviral
      gene transfer to overexpress BMP-2 can induce bone formation in vivo and heal a
      critically sized femoral defect in an athymic rat. The HPLA cells alone did not
      induce significant bone formation. However, when combined with an osteoinductive
      factor these cells may be an effective method for enhancing bone healing and the
      tissue engineering of bone.

PMID- 15738668
TI  - Biological evaluation of chitosan salts cross-linked to genipin as a cell
      scaffold for disk tissue engineering.
AB  - Degenerative disc disease has been implicated as a major component of spine
      pathology. However, although biological repair of the degenerate disk would be
      the ideal treatment, there is no universally accepted scaffold for tissue
      engineering of the intervertebral disk. To help remedy this, we investigated the
      gelation kinetics of various concentrations (2.5 to 10%) of two water-soluble
      chitosan chlorides (low molecular weight Protasan UP CL113 and high molecular
      weight Protasan UP CL213) and two chitosan glutamates (low molecular weight
      Protasan UP G113 and high molecular weight Protasan UP G213). Various
      concentrations (5 to 20%) of genipin, a naturally occurring cross-linking reagent
      used in herbal medicine and in the fabrication of food dyes, were used to prepare
      cross-linked chitosan hydrogels. The results show that 2.5% Protasan UP G213
      cross-linked to 5% genipin was the best candidate. This formulation gelled
      fastest at 37 degrees C, and maintained 95% viability of encapsulated cultured
      disk cells. The gel did not produce an inflammatory reaction when injected
      subcutaneously into C57BL/6 mice and is therefore biocompatible. Most
      importantly, when injected into the degenerated nucleus pulposus of human
      cadaveric intervertebral disk, the gel flowed into the clefts without leakage.
      This study demonstrates that 2.5% Protasan UP G213 cross-linked to 5% genipin
      might be a promising scaffold for disk tissue engineering.

PMID- 15738669
TI  - Evaluation of medium supplemented with insulin-transferrin-selenium for culture
      of primary bovine calf chondrocytes in three-dimensional hydrogel scaffolds.
AB  - Insulin-transferrin-selenium (ITS) was investigated as a complete or partial
      replacement for fetal bovine serum (FBS) during in vitro culture of bovine calf
      chondrocytes in hydrogel scaffolds. Chondrocyte-seeded agarose and self
      assembling peptide hydrogels were maintained in Dulbecco's modified Eagle's
      medium plus 10% FBS, 1% ITS plus 0.2% FBS, or 1% ITS and evaluated for
      biosynthesis, cell division, and surface outgrowth of fibroblastic-like cells and
      fibrous capsule formation over several weeks of culture. In peptide hydrogels,
      cells cultured in ITS plus 0.2% FBS medium exhibited high rates of biosynthesis
      and showed similar cell division trends as seen in 10% FBS cultures. ITS medium
      alone did not support glycosaminoglycan accumulation beyond 5 days of culture,
      and cell division was less than that in both serum-containing cultures. Extensive
      cellular outgrowth and fibrous capsule formation were observed in 10% FBS medium,
      whereas little outgrowth was observed in ITS plus 0.2% FBS and none was seen in
      ITS medium alone. In agarose hydrogels, chondrocyte biosynthesis and cell
      division in ITS medium were similar to that in 10% serum culture over 5 weeks,
      and cellular outgrowth was eliminated. Taken together, ITS was suitable as a
      partial (peptide) or complete (agarose) substitute for serum, and also provided
      the benefit of reducing or eliminating cell outgrowth and fibrous capsule
      formation on the hydrogel surface.

PMID- 15738670
TI  - Osteogenesis with cryopreserved marrow mesenchymal cells.
AB  - Rat marrow cells were collected from the femurs of 7-week-old male rats (Fischer
      344), cultured in 75-cm2 flasks for 10 days, released with trypsin, and then
      frozen and stored at -196 degrees C in liquid nitrogen. Three months later, the
      cryopreserved marrow cells were rapidly thawed and cultured in porous
      hydroxyapatite (HA) blocks in osteogenic medium containing 10 mM sodium beta
      glycerophosphate, vitamin C phosphate (82 microg/mL), and 10 nM dexamethasone.
      After 2 weeks of subculture, cultured cells-HA constructs were subcutaneously
      implanted into syngeneic rats. The constructs were harvested 2 and 4 weeks
      postimplantation and examined by histological, biochemical, and genetic analyses.
      Histological examination showed extensive bone formation in the HA pores. High
      alkaline phosphatase (ALP) activity and high osteocalcin content were detected in
      the constructs. Expression of ALP and osteocalcin mRNA was observed at both 2 and
      4 weeks. These results indicate that artificial bone prepared with cryopreserved
      cells had a marked osteogenic capacity.

PMID- 15738671
TI  - In vitro growth of human urinary tract smooth muscle cells on laminin and
      collagen type I-coated membranes under static and dynamic conditions.
AB  - This study investigates in vitro growth of human urinary tract smooth muscle
      cells under static conditions and mechanical stimulation. The cells were cultured
      on collagen type I- and laminin-coated silicon membranes. Using a Flexcell device
      for mechanical stimulation, a cyclic strain of 0-20% was applied in a strain
      stress-time model (stretch, 104 min relaxation, 15 s), imitating physiological
      bladder filling and voiding. Cell proliferation and alpha-actin, calponin, and
      caldesmon phenotype marker expression were analyzed. Nonstretched cells showed
      significant better growth on laminin during the first 8 days, thereafter becoming
      comparable to cells grown on collagen type I. Cyclic strain significantly reduced
      cell growth on both surfaces; however, better growth was observed on laminin.
      Neither the type of surface nor mechanical stimulation influenced the expression
      pattern of phenotype markers; alpha-actin was predominantly expressed. Coating
      with the extracellular matrix protein laminin improved in vitro growth of human
      urinary tract smooth muscle cells.

PMID- 15738672
TI  - Primary culture of polarized human salivary epithelial cells for use in
      developing an artificial salivary gland.
AB  - Therapeutic irradiation for head and neck cancer, and the autoimmune disease
      Sjogren's syndrome, lead to loss of salivary parenchyma. They are the two main
      causes of irreversible salivary gland hypofunction. Such patients cannot produce
      adequate levels of saliva, leading to considerable morbidity. We are working to
      develop an artificial salivary gland for such patients. A major problem in this
      endeavor has been the difficulty in obtaining a suitable autologous cellular
      component. This article describes a method of culturing and expanding primary
      salivary cells obtained from human submandibular glands (huSMGs) that is serum
      free and yields cells that are epithelial in nature. These include morphological
      (light and transmission electron microscopy [TEM]), protein expression
      (immunologically positive for ZO-1, claudin-1, and E-cadherin), and functional
      evidence. Under confocal microscopy, huSMG cells show polarization and
      appropriately localize tight junction proteins. TEM micrographs show an absence
      of dense core granules, but confirm the presence of tight and intermediate
      junctions and desmosomes between the cells. Functional assays showed that huSMG
      cells have high transepithelial electrical resistance and low rates of
      paracellular fluid movement. Additionally, huSMG cells show a normal karyotype
      without any morphological or numerical abnormalities, and most closely resemble
      striated and excretory duct cells in appearance. We conclude that this culture
      method for obtaining autologous human salivary cells should be useful in
      developing an artificial salivary gland.

PMID- 15738673
TI  - The challenge to measure cell proliferation in two and three dimensions.
AB  - Various assays, using different strategies, are available for assessing cultured
      cell proliferation. These include measurement of metabolic activity (tetrazolium
      salts and alamarBlue), DNA quantification using fluorophores (Hoechst 33258 and
      PicoGreen), uptake of radioactively-labeled DNA precursors such as [3H]thymidine,
      and physical counting (hemocytometer). These assays are well established in
      characterizing cell proliferation in two-dimensional (2D), monolayer cultures of
      low cell densities. However, increasing interest in 3D cultures has prompted the
      need to evaluate the effectiveness of using these assays in high cell density or
      3D cultures. We show here that typical cell proliferation assays do not
      necessarily correlate linearly with increasing cell densities or between 2D and
      3D cultures, and are either not suitable or only rough approximations in
      quantifying actual cell numbers in a culture. Prudent choice of techniques and
      careful interpretation of data are therefore recommended when measuring cell
      proliferation in high cell density and 3D cultures.

PMID- 15738674
TI  - Role for interleukin 1alpha in the inhibition of chondrogenesis in autologous
      implants using polyglycolic acid-polylactic acid scaffolds.
AB  - Significant challenges remain in generating tissue-engineered cartilage in
      immunocompetent animals. Scaffold materials such as polyglycolic acid lead to
      significant inflammatory reactions, inhibiting homogeneous matrix synthesis. This
      study examined the generation of tissue-engineered cartilage, using a
      polyglycolic acid-polylactic acid copolymer (Ethisorb; Ethicon, Norderstedt,
      Germany) in an autologous immunocompetent pig model. The goals of this study were
      to determine the role of interleukin 1alpha (IL-1alpha) in this system and to
      assess the effect of serum treatment on tissue generation. Porcine auricular
      chondrocytes were seeded onto Ethisorb disks cultured for 1 week in medium
      supplemented with either fetal bovine serum or serum-free insulin-transferrin
      selenium supplement. Specimens were implanted autogenously in pigs with unseeded
      scaffolds as controls. After 1, 4, or 8 weeks, six specimens from each group were
      explanted and analyzed histologically (hematoxylin and eosin, safranin O,
      trichrome, and Verhoeff's staining) and biochemically (glycosaminoglycan
      content). The presence and distribution of IL-1alpha were assessed by
      immunohistochemistry. Histology revealed acute inflammation surrounding degrading
      scaffold. Cartilage formation was observed as early as 1 week after implantation
      and continued to increase with time; however, homogeneous matrix synthesis was
      not present in any of the specimens. Strong IL-1alpha expression was detected in
      chondrocytes at the implant periphery and in cells in the vicinity of degrading
      polymer. Histologically there was no significant difference between the
      experimental groups with respect to the amount of matrix synthesis or
      inflammatory infiltration. The glycosaminoglycan content was significantly higher
      in the serum-free group. These results suggest that inflammatory reactions
      against scaffold materials and serum components lead to the production of
      cytokines such as IL-1alpha that may inhibit cartilage tissue formation in
      autologous transplant models.

PMID- 15738675
TI  - Bioresponsive phosphoester hydrogels for bone tissue engineering.
AB  - Bioresponsive and intelligent biomaterials are a vehicle for manipulating cell
      function to promote tissue development and/or tissue engineering. A
      photopolymerized hydrogel based on a phosphoester- poly(ethylene glycol) polymer
      (PhosPEG) was synthesized for application to marrow-derived mesenchymal stem cell
      (MSC) encapsulation and tissue engineering of bone. The phosphor-containing
      hydrogels were hydrolytically degradable and the rate of degradation increased in
      the presence of a bone-derived enzyme, alkaline phosphatase. Gene expression and
      protein analysis of encapsulated MSCs demonstrated that PhosPEG-PEG cogels
      containing an intermediate concentration of phosphorus promoted the gene
      expression of bone-specific markers including type I collagen, alkaline
      phosphatase, and osteonectin, without the addition of growth factors or other
      biological agents, compared with pure poly(ethylene glycol)-based gels. Secretion
      of alkaline phosphatase, osteocalcin, and osteonectin protein was also increased
      in the PhosPEG cogels. Mineralization of gels increased in the presence of
      phosphorus in both cellular and acellular constructs compared with PEG gels. In
      summary, phosphate-PEG-derived hydrogels increase gene expression of bone
      specific markers, secretion of bone-related matrix, and mineralization and may
      have a potential impact on bone-engineering therapies.

PMID- 15738676
TI  - Ovine model for engineering bone segments.
AB  - We propose a large animal model for bone tissue engineering that yields
      quantitative data and simulates clinical methods and tissue needs. Skeletally
      mature domestic sheep (n = 20) were each implanted with three rectangular (1 x 1
      x 4 cm), hollow tissue-molding chambers that were empty (control) or filled with
      equal weights (6.71-6.78 g) of particulate autologous bone graft (MBG) or bone
      graft that was autoclaved to denature stored growth factors (DeMBG). MBG provided
      scaffold and bioactive factors, and DeMBG provided only scaffold. The chambers
      were enclosed on five sides and securely implanted so that the open face was
      apposed to the osteogenic (i.e., cambium) layer of the rib periosteum for 3, 6,
      9, 12, or 24 weeks, after which the chambers were harvested and the contents
      analyzed. Each chamber contained osseous and fibrovascular tissue. MBG-containing
      chambers had the best maintenance of tissue volume compared with DeMBG-containing
      or empty chambers, but it still decreased steadily over time. Despite this, the
      MBG-containing chambers showed continuous active bone formation. There was
      increasing calcified tissue with penetration of osteogenesis up to a mean of 0.75
      +/- 0.15 cm from the periosteum by 9 weeks, and the osteogenic area peaked at
      0.59 +/- 0.13 cm2 by 12 weeks. Using quantitative measures that reflect clinical
      needs (i.e., tissue volume, shape, and quality), it was possible to distinguish
      differences in performance associated with manipulation of implanted scaffold and
      bioactive factors. This ovine model may serve as a useful tool to develop
      clinical osseous tissue-engineering strategies.

PMID- 15738677
TI  - Human endothelial cell interaction with biomimetic surfactant polymers containing
      Peptide ligands from the heparin binding domain of fibronectin.
AB  - Biomimetic materials that mimic the extracellular matrix (ECM) provide a means to
      control cellular functions such as adhesion and growth, which are vital to
      successful engineering of tissue-incorporated biomaterials. Novel "ECM-like"
      biomimetic surfactant polymers consisting of a poly(vinyl amine) backbone with
      pendant cell-adhesive peptides derived from one of the heparin-binding domains of
      fibronectin were developed to improve endothelial cell adhesion and growth on
      vascular biomaterials. Heparin-binding peptide (HBP) sequences, alone and in
      combination with RGD peptides, were examined for their ability to promote human
      pulmonary artery endothelial cell (HPAEC) adhesion and growth (HBP1, WQPPRARI;
      HBP2, SPPRRARVT; HBP1:RGD; and HBP2:RGD) and compared with cell adhesion and
      growth on fibronectin and on negative control polymer surfaces in which alanines
      were substituted for the positively charged arginine residues in the two
      peptides. The results showed that HPAECs adhered and spread equally well on all
      HBP-containing polymers and the positive fibronectin control, showing similar
      stress fiber and focal adhesion formation. However, the HBP alone was unable to
      support long-term HPAEC growth and survival, showing a loss of focal adhesions
      and cytoskeletal disorganization by 24 h after seeding. With the addition of RGD,
      the surfaces behaved similarly or better than fibronectin. The negative control
      polymers showed little to no initial cell attachment, and the addition of soluble
      heparin to the medium reduced initial cell adhesion on both the HBP2 and HBP2:RGD
      surfaces. These results indicate that the HBP surfaces promote initial HPAEC
      adhesion and spreading, but not long-term survival.

PMID- 15738678
TI  - Species variability in the differentiation potential of in vitro-expanded
      articular chondrocytes restricts predictive studies on cartilage repair using
      animal models.
AB  - Autologous chondrocyte implantation is currently applied in clinics as an
      innovative tool for articular cartilage repair. Animal models have been and still
      are being used to validate and further improve the technique. However, in various
      species, the outcome varies from hyaline-like cartilage to fibrocartilage. This
      may be due partly to the spontaneous dedifferentiation of chondrocytes once
      cultured in vitro. Here we assessed whether the extent of dedifferentiation
      varies between species and we hypothesized that the level of chondrocyte
      phenotype stability during expansion may contribute to the maintenance of their
      chondrogenic commitment and redifferentiation potential. Condyle chondrocytes
      were harvested from sheep, dog, and human, and expanded for 1, 6, or 12 cell
      duplications. At each interval, cell phenotype was monitored (morphology and
      biosynthesis of cartilage markers) and redifferentiation was assessed by an in
      vitro assay of chondrogenesis in micromass pellet and an in vivo assay of ectopic
      cartilage formation in immunodeficient mice. Results indicate that, during
      culture, the sheep chondrocyte phenotype is maintained better than that of human
      chondrocytes, which in turn dedifferentiate to a lesser extent than dog
      chondrocytes Accordingly, after expansion, sheep chondrocytes spontaneously
      reform hyaline-like cartilage; human chondrocytes redifferentiate only under
      stimulation with chondrogenic inducers whereas, after a few passages, dog
      chondrocytes lose any capacity to redifferentiate regardless of the presence of
      inducers. Thus, conditions allowing cartilage formation in one species are not
      necessarily transposable to other species. Therefore, results with animal models
      should be cautiously applied to humans. In addition, for tissue-engineering
      purposes, the number of cell duplications must be, for each species, carefully
      monitored to remain in the range of amplification allowing redifferentiation and
      chondrogenesis.

PMID- 15738679
TI  - Surface motion upregulates superficial zone protein and hyaluronan production in
      chondrocyte-seeded three-dimensional scaffolds.
AB  - A cartilage engineering bioreactor has been developed that provides joint
      specific kinematics. This study investigated the effect of articular motion on
      the gene expression of superficial zone protein (SZP) and hyaluronan synthases
      (HASs) and on the release of SZP and hyaluronan of chondrocytes seeded onto
      biodegradable scaffolds. Cylindrical (8 x 4 mm) porous polyurethane scaffolds
      were seeded with bovine articular chondrocytes and subjected to static or dynamic
      compression, with and without articulation against a ceramic hip ball. After
      loading, the mRNA expression of SZP and HASs was analyzed, and SZP
      immunoreactivity and hyaluronan concentration of conditioned media were
      determined. Surface motion significantly upregulated the mRNA expression of SZP
      and HASs. Axial compression alone had no effect on SZP and increased HAS mRNA
      only at high strain amplitude. SZP was immunodetected only in the media of
      constructs exposed to surface motion. The release of hyaluronan into the culture
      medium was significantly enhanced by surface motion. These results indicate that
      specific stimuli that mimic the kinematics of natural joints, such as articular
      motion, may promote the development of a functional articular surface-synovial
      interface.

PMID- 15738680
TI  - Diffusion limits of an in vitro thick prevascularized tissue.
AB  - Although tissue engineering promises to replace or restore lost function to
      nearly every tissue in the body, successful applications are currently limited to
      tissue less than 2 mm in thickness. in vivo capillary networks deliver oxygen and
      nutrients to thicker (> 2 mm) tissues, suggesting that introduction of a
      preformed in vitro vascular network may be a useful strategy for engineered
      tissues. This article describes a system for generating capillary-like networks
      within a thick fibrin matrix. Human umbilical vein endothelial cells, growing on
      the surface of microcarrier beads, were embedded in fibrin gels a known distance
      (Delta = 1.8-4.5 mm) from a monolayer of human dermal fibroblasts. The distance
      of the growth medium, which contained vascular endothelial growth factor and
      basic fibroblast growth factor, from the beads, C, was varied from 2.7 to 7.2 mm.
      Capillaries with visible lumens sprouted in 2-3 days, reaching lengths that
      exceeded 500 microm within 6-8 days. On day 7, capillary network formation was
      largely independent of C; however, a strong inverse correlation with Delta was
      observed, with the maximum network formation at Delta = 1.8 mm. Surprisingly, the
      thickness of the gel was not a limiting factor for oxygen diffusion as these
      tissue constructs retained a relatively high oxygen tension of > 125 mmHg. We
      conclude that diffusion of oxygen in vitro is not limiting, allowing the
      development of tissue constructs on the order of centimeters in thickness. In
      addition, diffusion of fibroblast-derived soluble mediators is necessary for
      stable capillary formation, but is significantly impeded relative to that of
      nutrients present in the medium.

PMID- 15738681
TI  - Matrix metalloproteinase 9 facilitates collagen remodeling and angiogenesis for
      vascular constructs.
AB  - Degradation of the extracellular matrix, facilitated by matrix metalloproteinases
      (MMPs), can lead to mechanical failure of vascular constructs, suggesting that
      MMP inhibition could improve survival of constructs. Therefore, we investigated
      the role of MMP-9 in collagen remodeling in vitro, focusing on the three major
      steps of production, degradation, and organization. Because an adequate blood
      supply is essential for survival of tissue-engineered constructs, we also
      evaluated the influence of MMP-9 deficiency on angiogenesis in vivo by
      implantation of thin biodegradable polymer scaffolds. Using aortic smooth muscle
      cells (SMCs) from wild-type and genetically deficient (9KO) mice, we examined the
      role of MMP-9 in collagen mRNA expression and protein accumulation, both with and
      without ascorbic acid treatment. We measured collagen assembly in a
      fibrillogenesis assay. We investigated in vivo angiogenesis and cell invasion,
      using fluorescence microangiography and histology. MMP-9 deficiency did not
      affect collagen mRNA production or polymer scaffold degradation, but collagen
      accumulation was greater in cultures of 9KO SMCs than in wild-type SMCs. Both MMP
      9 deficiency and chemical inhibition impaired collagen degradation. Ascorbic acid
      treatment enhanced collagen production by 9KO SMCs compared with wild-type SMCs
      at 3 days, but by 7 days this effect was reversed. MMP-9 improved fibrillogenesis
      of collagen, significantly more on ascorbic acid treatment. MMP-9 deficiency
      dramatically decreased inflammatory cell invasion, but also capillary formation
      within biodegradable polymer scaffolds in vivo. Our data suggest that MMP
      inhibition, by impairing collagen organization and angiogenesis, might have
      detrimental effects on the survival of vascular constructs.

PMID- 15738682
TI  - Comparison of three myofibroblast cell sources for the tissue engineering of
      cardiac valves.
AB  - The objective of this study was to evaluate the capacity of three clinically
      useful tissue sources: tricuspid valve leaflet (TVL), carotid artery (CA), and
      jugular vein (JV), to generate myofibroblasts for potential use in a tissue
      engineered cardiac valve replacement. Tissue biopsies of clinically appropriate
      sizes obtained from juvenile sheep were used for this work. Cells obtained from
      all three tissue sources exhibited a myofibroblast phenotype in vitro, as
      demonstrated by their immunoreactivity with antibodies directed against vimentin,
      alpha-smooth muscle actin, fibronectin, and chondroitin sulfate. Protein
      synthesis characteristics were defined for the key extracellular matrix
      components: collagen, glycosaminoglycans, and elastin. Among the three sources,
      JV generated the highest numbers of cells, and JV cells produced the largest
      amount of collagen per cell. These data suggest that venous tissue, with its
      relative ease of accessibility, may generate myofibroblasts potentially useful
      for the interstitial cellular component of a tissue-engineered cardiac valve.

PMID- 15738683
TI  - Endothelialized microvasculature based on a biodegradable elastomer.
AB  - Vital organs maintain dense microvasculature to sustain the proper function of
      their cells. For tissue- engineered organs to function properly, artificial
      capillary networks must be developed. We have microfabricated capillary networks
      with a biodegradable and biocompatible elastomer, poly(glycerol sebacate) (PGS).
      We etched capillary patterns onto silicon wafers by standard micro
      electromechanical systems (MEMS) techniques. The resultant silicon wafers served
      as micromolds for the devices. We bond the patterned PGS film with a flat film to
      create capillary networks that were perfused with a syringe pump at a
      physiological flow rate. The devices were endothelialized under flow conditions,
      and part of the lumens reached confluence within 14 days of culture. This
      approach may lead to tissue-engineered microvasculature that is critical in vital
      organs engineering.

PMID- 15738684
TI  - Continuous transforming growth factor beta1 secretion by cell-mediated gene
      therapy maintains chondrocyte redifferentiation.
AB  - One of the most important factors in the production of cartilage is transforming
      growth factor beta1 (TGF-beta1). To obtain sustained release of TGF-beta1, a cell
      mediated gene therapy technique was introduced. We infected chondrocytes with a
      retroviral vector carrying the TGF-beta1 gene. The single clone derivative showed
      sustained TGF-beta1 secretion. It also showed constitutive type II collagen
      expression. Whereas the TGF-beta1 protein itself is unable to induce formation of
      cartilage in vivo, human chondrocytes engineered to express a retroviral vector
      encoding TGF-beta1 showed cartilage formation in vivo when cells were injected
      into nude mice intradermally. These data suggest that cell-mediated gene therapy
      using TGF-beta1 as a transgene would be a promising treatment for osteoarthritis.

PMID- 15738685
TI  - Biomimetic three-dimensional cultures significantly increase hematopoietic
      differentiation efficacy of embryonic stem cells.
AB  - Stem cell-based tissue engineering is a promising technology in the effort to
      create functional tissues of choice. To establish an efficient approach for
      generating hematopoietic cell lineages directly from embryonic stem (ES) cells
      and to study the effects of three-dimensional (3D) biomaterials on ES cell
      differentiation, we cultured mouse ES cells on 3D, highly porous, biomimetic
      scaffolds. Cell differentiation was evaluated by microscopy and flow cytometry
      analysis with a variety of hematopoiesis- specific markers. Our data indicate
      that ES cells differentiated on porous 3D scaffold structures developed embryoid
      bodies (EBs) similar to those in traditional two-dimensional (2D) cultures;
      however, unlike 2D differentiation, these EBs integrated with the scaffold and
      appeared embedded in a network of extracellular matrix. Most significantly, the
      efficiency of hematopoietic precursor cell (HPC) generation on 3D, as indicated
      by the expression of various HPC-specific surface markers (CD34, Sca-1, Flk-1,
      and c-Kit) and colony-forming cell (CFC) assays, was reproducibly increased
      (about 2-fold) over their 2D counterparts. Comparison of static and dynamic 3D
      cultures demonstrated that spinner flask technology also contributed to the
      higher hematopoietic differentiation efficiency of ES cells seeded on scaffolds.
      Continued differentiation of 3D-derived HPCs into the myeloid lineage
      demonstrated increased efficiency (2-fold) of generating myeloid compared with
      differentiation from 2D-derived HPCs.

PMID- 15738686
TI  - Use of a biphasic graft constructed with chondrocytes overlying a beta-tricalcium
      phosphate block in the treatment of rabbit osteochondral defects.
AB  - To evaluate the ability of a biphasic construct to repair osteochondral defects
      in articular cartilage, plugs made of chondrocytes in collagen gel overlying a
      resorbable porous beta-tricalcium phosphate (TCP) block were implanted into
      defects in rabbit knees. The repair tissue was evaluated at 8, 12, and 30 weeks.
      Eight weeks after implantation of the biphasic construct, histologic examination
      showed hyaline-like cartilage formation that was positive for safranin O and type
      II collagen. At 12 weeks, most of the beta-TCP was replaced by bone, with a small
      amount remaining in the underlying cartilage. In the cell-seeded layer, the newly
      formed middle and deep cartilage adjacent to the subchondral bone stained with
      safranin O, but no staining was observed in the superficial layer. In addition,
      cell morphology was distinctly different from the deep levels of the reparative
      cartilage, with hypertrophic cells at the bottom of the cartilaginous layer. At
      30 weeks, beta-TCP had completely resorbed and a tidemark was observed in some
      areas. In contrast, controls (defects filled with a beta-TCP block alone) showed
      no cartilage formation but instead had subchondral bone formation. These findings
      indicate that beta-TCP-supported chondrocytes in collagen gel can partially
      repair isolated articular cartilage osteochondral defects.

PMID- 15738687
TI  - Liar, liar: internet faking but not frequency of use affects social skills, self
      esteem, social anxiety, and aggression.
AB  - Misuse of the Internet can affect various aspects of children's social lives. It
      was predicted that children who misrepresent themselves on the Internet would
      have less well-developed social skills, lower levels of self-esteem, and higher
      levels of social anxiety and aggression. The frequency of Internet use was also
      assessed. Students aged 11-16 years were recruited for the study from classes
      after obtaining consent. Questionnaires included a query of Internet behaviors,
      the Matson Evaluation of Social Skills with Youngsters Appropriate Social Skills
      and Inappropriate Assertiveness subscales, Rosenberg Self-esteem Scale, and the
      Social Anxiety Scale for Children-Revised. It was found that children who
      reported the most faking behavior on the Internet (e.g., pretending to be older)
      had poorer social skills, lower levels of self-esteem, higher levels of social
      anxiety, and higher levels of aggression. Frequency of use, however, did not
      affect these factors in the current study.

PMID- 15738688
TI  - Internet addiction: a review of current assessment techniques and potential
      assessment questions.
AB  - The concept of Internet addiction has been proposed as an explanation for
      uncontrollable and damaging use of the Internet. Symptoms of excessive Internet
      use have been compared to the criteria used to diagnose other addictions such as
      pathological gambling. Although criteria to diagnose this problem have been
      proposed, methods of assessing excessive Internet use are limited. A structured
      interview based on the criteria proposed by Beard and Wolf is proposed to aid in
      the assessment of "Internet addiction." This, in turn, could aid in the diagnosis
      and intervention of a client who enters treatment reporting difficulties with
      excessive Internet use.

PMID- 15738689
TI  - Physical interpersonal relationships and social anxiety among online game
      players.
AB  - Many online game players spend inordinate amounts of time in their favorite
      virtual worlds. A large percentage of these players are teenagers who show
      behaviors normally associated with physical addiction. Parents, educators, and
      social scientists are therefore saying that online games are sources of social
      problems. The authors surveyed 174 Taiwanese college-age online players to
      collect data on the potential effects of online games on the quality of
      interpersonal relationships and levels of social anxiety. According to the
      results, the quality of interpersonal relationships decreased and the amount of
      social anxiety increased as the amount of time spent playing online games
      increased.

PMID- 15738690
TI  - Gender and information and communication technologies (ICT) anxiety: male self
      assurance and female hesitation.
AB  - This article presents the results of a quantitative study (n = 1,058) of the
      gender divide in ICT attitudes. In general, females had more negative attitudes
      towards computers and the Internet than did men. Results indicate a positive
      relationship between ICT experience and ICT attitudes. This experience is
      measured by period of time using a computer and self-perceived computer and
      Internet experience. Further analyses on the impact of gender on this correlation
      of ICT experience and ICT attitudes were conducted by means of a multivariate
      model. General Linear Model (GLM) analysis revealed that there was a significant
      effect of gender, computer use, and self-perceived computer experience on
      computer anxiety attitudes, as well as several significant interaction effects.
      Males were found to have less computer anxiety than females; respondents who have
      used computers for a longer period of time and respondents with a higher self
      perception of experience also show less computer anxiety. However, the GLM plot
      shows that the influence of computer experience works in different ways for males
      and females. Computer experience has a positive impact on decreasing computer
      anxiety for men, but a similar effect was not found for women. The model was also
      tested for computer liking and Internet-liking factors.

PMID- 15738691
TI  - Stroop facilitation in tinnitus patients: an experiment conducted via the world
      wide web.
AB  - Cognitive mechanisms have been proposed to play an important role in tinnitus. In
      the present study, tinnitus participants were administered an emotional Stroop
      test via the Internet, incorporating words related to tinnitus concerns. In line
      with previous research using this Web-based version of the emotional Stroop test,
      faster color naming was demonstrated for concern-relevant words relative to
      neutral words. The present results thus provided support for a role for cognitive
      factors that are important for the understanding of tinnitus. However, future
      research is warranted in order to clarify the precise mechanisms involved in
      tinnitusrelated Stroop effects.

PMID- 15738692
TI  - Psychological predictors of problem mobile phone use.
AB  - Mobile phone use is banned or illegal under certain circumstances and in some
      jurisdictions. Nevertheless, some people still use their mobile phones despite
      recognized safety concerns, legislation, and informal bans. Drawing potential
      predictors from the addiction literature, this study sought to predict usage and,
      specifically, problematic mobile phone use from extraversion, self-esteem,
      neuroticism, gender, and age. To measure problem use, the Mobile Phone Problem
      Use Scale was devised and validated as a reliable self-report instrument, against
      the Addiction Potential Scale and overall mobile phone usage levels. Problem use
      was a function of age, extraversion, and low self-esteem, but not neuroticism. As
      extraverts are more likely to take risks, and young drivers feature prominently
      in automobile accidents, this study supports community concerns about mobile
      phone use, and identifies groups that should be targeted in any intervention
      campaigns.

PMID- 15738693
TI  - Flirting on the internet and the hickey: a hermeneutic.
AB  - Nowadays, erotic behaviour in cyberspace is customary. Online dating is a million
      dollar industry. Within the everyday politics of erotic-romantic relationships,
      however, males and females still blush in each other's presence, caress tenderly
      and trade hickeys. Mainstream social science researches cyber-behaviour
      voluminously, but totally ignores commonplace fleshy phenomena. Our study probes
      this discrepancy. What does it mean that virtual sex is winning the current war
      between desire and technology? Why is the 'flesh' becoming increasingly
      marginalized? To accomplish our aim, we use a phenomenological-hermeneutic
      method. Our basic results are two narratives: (1) interpretations about Internet
      flirting; and (2) descriptive finding about the hickey. Then, in order to reach
      general conclusions, we interpret the two studies in light of each other. It is a
      double hermeneutic. The two target phenomena share the similarity of manifesting
      the same "lovemap," "solicitation and allure." But they also differ sharply.
      Internet flirting exemplifies "mirror enchantment"; whereas the hickey showcases
      a phenomenology of the eyes, touch, dialogue and physical presence. We explain
      Western culture's preference for technology to the neglect of 'live' embodiment
      as manifesting a repetition of Platonic-Christendom's contempt for the flesh and
      horror of passionate tenderness. Our culture, on the cusp between modernity and
      post-modernity, displays dread concerning the flesh by obsessive concerns with
      safety-security and with modulating excesses. Are not absolute control and
      perfect security, however, merely illusions? We showcase the positive aspects of
      seemingly unsafe values: psychological vulnerability, daring, and risk.

PMID- 15738694
TI  - Teen internet use: relating social perceptions and cognitive models to behavior.
AB  - In order to provide Internet researchers with a better understanding of how and
      why individuals adopt some online behaviors and not others, this study targets
      teenage Internet users to examine the relationships among social influence and
      self-regulatory models as mechanisms to the behavior of Internet use.
      Information, entertainment, and social online activities are presented as three
      distinct uses of the Internet so corresponding behavioral models of adoption
      could be tested. Results from 173 high school students indicate that direct and
      vicarious social perceptions significantly influence self-regulation, which
      subsequently has an effect on use. Using path analyses to test the direct and
      indirect theoretical relationships among these constructs, the data indicates
      that while clearly fitting two of the three models tested, three unique processes
      to adoption are evident.

PMID- 15738695
TI  - Virtual reality therapy versus cognitive behavior therapy for social phobia: a
      preliminary controlled study.
AB  - Social phobia is one of the most frequent mental disorders and is accessible to
      two forms of scientifically validated treatments: anti-depressant drugs and
      cognitive behavior therapies (CBT). In this last case, graded exposure to feared
      social situations is one of the fundamental therapeutic ingredients. Virtual
      reality technologies are an interesting alternative to the standard exposure in
      social phobia, especially since studies have shown its usefulness for the fear of
      public speaking. This paper reports a preliminary study in which a virtual
      reality therapy (VRT), based on exposure to virtual environments, was used to
      treat social phobia. The sample consisted of 36 participants diagnosed with
      social phobia assigned to either VRT or a group-CBT (control condition). The
      virtual environments used in the treatment recreate four situations dealing with
      social anxiety: performance, intimacy, scrutiny, and assertiveness. With the help
      of the therapist, the patient learns adapted cognitions and behaviors in order to
      reduce anxiety in the corresponding real situations. Both treatments lasted 12
      weeks, and sessions were delivered according to a treatment manual. Results
      showed statistically and clinically significant improvement in both conditions.
      The effect-sizes comparing the efficacy of VRT to the control traditional group
      CBT revealed that the differences between the two treatments are trivial.

PMID- 15738696
TI  - Personality of people using chat: an on-line research.
AB  - Conflicting claims have been presented in the literature about on-line management
      of personal relationships. The current research, carried out in a substantially
      descriptive design, aimed to consider psychological and social features of a
      particular electronic environment, the Chat room. One hundred fifty-eight
      participants filled out an on-line questionnaire set, designed to investigate the
      personality traits and the prevailing interpersonal values of those participants
      who set up interpersonal relationships on-line. The Web research showed that, if
      sampling control and validity assessment were provided, it could be a valid
      alternative to a more traditional paper-based procedure. The results highlighted
      that Chat users were not an homogenous group, but were composed of different
      personality types. Basically, however, this specific virtual environment proved
      to be crowded with rather close individuals, who were looking for independence
      but who needed also to be supported and encouraged. They created deep on-line
      relationships, but these remained limited to the virtual world.

PMID- 15738699
TI  - Editorial: symposium on algorithms for continuous glucose monitoring and control.

PMID- 15738700
TI  - Hypoglycemia prediction and detection using optimal estimation.
AB  - Patients with diabetes play with a double-edged sword when it comes to deciding
      glucose and A1c target levels. On the one side, tight control has been shown to
      be crucial in avoiding long-term complications; on the other, tighter control
      leads to an increased risk of iatrogenic hypoglycemia, which is compounded when
      hypoglycemia unawareness sets in. Development of continuous glucose monitoring
      systems has led to the possibility of being able not only to detect hypoglycemic
      episodes, but to make predictions based on trends that would allow the patient to
      take preemptive action to entirely avoid the condition. Using an optimal
      estimation theory approach to hypoglycemia prediction, we demonstrate the effect
      of measurement sampling frequency, threshold level, and prediction horizon on the
      sensitivity and specificity of the predictions. We discuss how optimal estimators
      can be tuned to trade-off the false alarm rate with the rate of missed predicted
      hypoglycemic episodes. We also suggest the use of different alarm levels as a
      function of current and future estimates of glucose and the hypoglycemic
      threshold and prediction horizon.

PMID- 15738701
TI  - The extended Kalman filter for continuous glucose monitoring.
AB  - Glucose monitoring is a problem with evolving solutions using sensors and data
      processing techniques that are continually improving. This paper presents the
      development and application of the extended Kalman filter to the problem of real
      time estimation of blood glucose levels and is consistent with sensors based on
      optical, electrical, or chemical processes. The structure of the extended Kalman
      filter provides the capability to systematically accommodate new information as
      it develops. This flexibility and the potential for performance improvement are
      demonstrated by processing patient data files generated using the Medtronic
      (Northridge, CA) MiniMed continuous glucose monitoring system (CGMS).

PMID- 15738702
TI  - A critical assessment of algorithms and challenges in the development of a closed
      loop artificial pancreas.
AB  - The development of an artificial pancreas is placed in the context of the history
      of the field of feedback control systems, beginning with the water clock of
      ancient Greece, and including a discussion of current efforts in the control of
      complex systems. The first generation of artificial pancreas devices included two
      manipulated variables (insulin and glucose infusion) and nonlinear functions of
      the error (difference between desired and measured glucose concentration) to
      minimize hyperglycemia while avoiding hypoglycemia. Dynamic lags between insulin
      infusion and glucose measurement were relatively small for these intravenous
      based systems. Advances in continuous glucose sensing, fast-acting insulin
      analogs, and a mature insulin pump market bring us close to commercial
      realization of a closed-loop artificial pancreas. Model predictive control is
      discussed in-depth as an approach that is well suited for a closed-loop
      artificial pancreas. A major challenge that remains is handling an unknown
      glucose disturbance (meal), and an approach is proposed to base a current insulin
      infusion action on the predicted effect of a meal on future glucose values.
      Better "meal models" are needed, as a limited knowledge of the effect of a meal
      on the future glucose values limits the performance of any control algorithm.

PMID- 15738703
TI  - Run-to-run control of meal-related insulin dosing.
AB  - BACKGROUND: This study was designed to determine if it was feasible to use a run
      to-run algorithm to improve postprandial glucose concentrations in individuals
      with type 1 diabetes mellitus (T1DM). METHODS: Fourteen subjects were recruited
      for this 10-week study. During the initial phases of the study, the following
      information was derived for each subject: basal insulin infusion rates, insulin
      to-carbohydrate ratios, insulin correction factors for hyperglycemia, and insulin
      sensitivities. During the final phases, the algorithm was used to suggest
      preprandial insulin doses, with a goal of bringing the postprandial glucose into
      a predetermined target range within 3-7 days. RESULTS: In the single-meal phase
      (phase 5), 33% of the subject-meal responses were convergent in 3-4 days to a
      clinically acceptable range, 33% always stayed in range, and 33% had divergent
      responses, incorrect sensitivities, and/or other mitigating circumstances. In the
      three-meal phase (phase 6), 41% of the subject-meal responses were convergent in
      3-4 days to a clinically acceptable range, 26% were always in range, and 33% had
      divergent responses, incorrect sensitivities, and/or other mitigating
      circumstances. CONCLUSIONS: Overall, we were able to safely demonstrate that run
      to-run control can be used to manage meal-related insulin in subjects with T1DM.

PMID- 15738704
TI  - The Intelligent Dosing System: application for insulin therapy and diabetes
      management.
AB  - Diabetes mellitus is an increasing public health problem. Insulin is an essential
      tool in the management of hyperglycemia, but methods of dose adjustment are
      purely empirical. The Intelligent Dosing System (IDS, Dimensional Dosing Systems,
      Inc., Wexford, PA) is a software suite that incorporates patient-specific, dose
      response data in a mathematical model and then calculates the new dose of the
      medication needed to achieve the next desired therapeutic goal. We discuss the
      application of the IDS in insulin management. The IDS concept and the initial
      modeling used to construct an insulin doser are reviewed first. Additional data
      are then provided on the use of the IDS for titrating insulin therapy in a
      clinical setting. Finally, recent modifications in the IDS software and future
      applications of this technology for insulin dosing and diabetes management are
      discussed.

PMID- 15738705
TI  - Grading system to assess clinical performance of closed-loop glucose control.
AB  - Closed-loop control of the glucose concentration in type 1 diabetes has been the
      subject of extensive research over the last 3 decades. Building on the recent
      progress in continuous glucose sensing techniques, several prototypes of a closed
      loop system have been developed. To complement existing measures of glucose
      control, we designed a grading system specifically designed to provide clinical
      assessment of closed-loop systems including that of glucose controllers. The
      system introduces six grades, A-F, describing the level of control and the
      therapeutic intervention during outside-meal and postprandial conditions. Grades
      A and B represent excellent and good glucose control, respectively, without the
      need for a corrective therapeutic action. Grade C represents suboptimal control
      with a recommendation for a corrective action. Grade D represents poor control
      requiring a corrective action. Grades E and F represent very poor and life
      threatening control, respectively, with a need for an immediate corrective action
      or requiring external assistance. The outcome of grading is the quantification of
      time spent in each grade. The grading system is exemplified using data obtained
      with a model predictive controller within an in silico simulation environment. We
      conclude that the grading system provides suitable means to assess efficacy and
      safety of glucose controllers complementing existing measures of glucose control.

PMID- 15738706
TI  - Pharmacokinetics of intravenous insulin delivery in humans with type 1 diabetes.
AB  - BACKGROUND: Insulin pharmacokinetics models describe the distribution and
      elimination of insulin in the body. These models can be useful in designing
      infusion schemes to produce a desired plasma insulin profile. METHODS: We
      evaluated the pharmacokinetics of intravenous insulin delivery in five human
      subjects with type 1 diabetes; one subject was studied on three separate
      occasions for a total of seven experiments. Each subject consumed an identical
      829 Kcal meal of solid food for breakfast and lunch, followed by exercise on a
      stationary bicycle. Regular human insulin was infused into a peripheral vein at a
      basal rate (0.5 U/h) for the entire study. Coinciding with the consumption of
      each meal, insulin was infused at a higher rate for 120 min (average dose 8.5 +/-
      2.1 U). The bolus dose was based upon preprandial and 60-min postprandial blood
      glucose measurements and a sliding scale regimen. Blood glucose levels were
      allowed to fluctuate throughout the protocol (mean 174 mg/dL, range 55-340
      mg/dL). Human insulin levels were measured from plasma samples obtained every 10
      min throughout the 8.5-h protocol. A total of 346 plasma samples were assayed to
      measure the concentration of human insulin. RESULTS AND CONCLUSIONS: Data were
      used to compare (previously developed) insulin kinetics models consisting of one,
      two, and three first-order linear differential equations. The ability of each
      model to simulate the input/output data (intravenous insulin infusion rate/plasma
      insulin concentration) was assessed. Our main finding is that the first-order
      linear insulin kinetics model was sufficient to describe the clinical data. The
      model had a fractional insulin loss rate of 0.112 +/- 0.063 min(1) and a
      distribution volume of 15.6 +/- 4.0 L.

PMID- 15738707
TI  - Modeling insulin action for development of a closed-loop artificial pancreas.
AB  - Three models of glucose homeostasis are compared in terms of their steady-state
      dose-response characteristics, how they characterize glucose distribution
      kinetics, and how they characterize the dynamics of insulin action. The three
      models [minimal model, AIDA (Automated Insulin Dosage Advisor), and a model by
      Sorensen] are used to discuss a wider variety of questions related to metabolic
      modeling. Simulations are performed comparing each model's response to an
      intravenous glucose tolerance test, with and without incremental insulin
      responses, to existing data in individuals with type 1 diabetes mellitus.
      Predicted changes in blood glucose following a subcutaneous bolus of insulin or
      an incremental increase in basal insulin delivery are simulated. From these
      results, the models are evaluated as potential candidates for simulating changes
      in treatment and developing a closed-loop insulin delivery algorithm. While no
      consensus model is proposed, relevant issues needing to be addressed are
      highlighted.

PMID- 15738709
TI  - Breath ethanol and acetone as indicators of serum glucose levels: an initial
      report.
AB  - BACKGROUND: Many volatile organic compounds are present in exhaled breath and may
      represent by-products of endogenous biological processes. Ethanol is produced via
      alcoholic fermentation of glucose by gut bacteria and yeast, while acetone
      derives from oxidations of free fatty acids, influenced by glucose metabolism. We
      hypothesized that the integrated analysis of breath ethanol and acetone would
      provide a good approximation of the blood glucose profile during a glucose load.
      METHODS: We collected simultaneous exhaled breath gas, ambient air, and serum
      glucose and insulin samples from 10 healthy volunteers at baseline and during an
      oral glucose tolerance test (OGTT) (ingestion of 75 g of glucose followed by 120
      min of sampling). Gas samples were analyzed by gas chromatography/mass
      spectrometry. RESULTS: Mean glucose values displayed a typical OGTT pattern
      (rapid increase, peak values at 30-60 min, and gradual return to near baseline by
      120 min). Breath ethanol displayed a similar pattern early in the test, with peak
      values at 30 min; this was followed by a fast return to basal levels by 60 min.
      Breath acetone decreased progressively below basal levels, with lowest readings
      obtained at 120 min. A multiple regression analysis of glucose, ethanol, and
      acetone was used to estimate glucose profiles that correlated with measured
      glucose values with an average individual correlation coefficient of 0.70, and
      not lower than 0.41 in any subject. CONCLUSION: The integrated analysis of
      multiple exhaled gases may serve as a marker of blood glucose levels. Further
      studies are needed to assess the usefulness of this method in different
      populations.

PMID- 15738710
TI  - Pharmacokinetics and pharmacodynamics of intranasal insulin administered to
      healthy subjects in escalating doses.
AB  - BACKGROUND: This exploratory study examined the pharmacokinetics and
      pharmacodynamics of a Bentley Pharmaceuticals, Inc. (North Hampton, NH)
      proprietary insulin formulation utilizing CPE-215 technology designed for
      intranasal administration. METHODS: Eight fasting healthy volunteers (four men,
      four women; body mass index, 23.6 +/- 1.7 kg/m2) received up to four doses of
      intranasal insulin at least 1 week apart. Serum insulin, C-peptide, and plasma
      glucose were measured in the 4-h period following administration. RESULTS: At
      doses of 18.75 IU and above, a rise in serum insulin levels accompanied by a
      decrease in plasma glucose and serum C-peptide levels was seen. Insulin levels
      peaked in 10-20 min and remained elevated for approximately 1 h, and the
      resultant hypoglycaemic effect peaked at 40 min and returned to normal 1.5-2 h
      post-dosing. At 25 IU (n = 11 doses; eight subjects with three replicates), there
      was a mean fall in plasma glucose of 20.49%; a greater fall in plasma glucose was
      seen with higher insulin doses. In addition, mean peak insulin levels increased
      with dose escalation. For the 25 IU dose (a single 90-microL spray), the maximum
      measured insulin concentration was 19.52 +/- 9.28 mIU/L, and the area under the
      concentration-time curve from 0 to 4 h was 19.06 +/- 5.56 mIU/L/h. Three subjects
      with repeated 25 IU doses demonstrated similarly reproducible peaks for maximum
      measured insulin concentration and for plasma glucose reductions. As seen with
      other insulin studies, the inter-individual responsiveness to insulin was
      variable. CONCLUSIONS: This intranasal formulation was generally well tolerated
      and demonstrated rapid onset of action and appropriate duration of action for the
      potential use in controlling postprandial hyperglycaemia.

PMID- 15738708
TI  - Accuracy of the modified Continuous Glucose Monitoring System (CGMS) sensor in an
      outpatient setting: results from a diabetes research in children network
      (DirecNet) study.
AB  - OBJECTIVE: We previously reported the results of an inpatient accuracy study in
      children with type 1 diabetes using the Continuous Glucose Monitoring System
      (CGMS, Medtronic MiniMed, Northridge, CA). During the course of that study, a new
      process was implemented for manufacturing the CGMS sensor. Accuracy from the
      resulting modified sensor used by only 14 children was significantly better than
      the original version [median relative absolute difference (RAD), 11% vs. 19%; P <
      0.001]. Baseline data from a subsequent outpatient study provide an opportunity
      to further assess the accuracy of the modified sensor in a much larger sample of
      children with type 1 diabetes. RESEARCH DESIGN AND METHODS: As part of a
      randomized trial to assess the utility of the GlucoWatch G2 Biographer (Cygnus,
      Inc., Redwood City, CA), 200 children with type 1 diabetes were instructed to
      wear a CGMS for 48-72 h in an outpatient setting at baseline. Glucose
      measurements from a OneTouch UltraSmart (Lifescan, Inc., Milpitas, CA) home
      glucose meter were downloaded and used as reference values to calculate accuracy
      measures. RESULTS: The overall median RAD was 12%. Accuracy was better during
      hyperglycemia than during hypoglycemia (median RAD, 10% vs. 20%; P < 0.001) and
      on optimal versus non-optimal days but did not vary significantly by the number
      of calibrations entered. CONCLUSIONS: These data confirm the improved accuracy
      previously reported for the modified version of the CGMS sensor.

PMID- 15738711
TI  - Minimally invasive extraction of dermal interstitial fluid for glucose monitoring
      using microneedles.
AB  - BACKGROUND: Compliance with glucose monitoring by patients with diabetes is poor
      because of the pain and inconvenience of conventional blood collection using
      lancets. To improve compliance, and thereby reduce morbidity and mortality
      associated with poor glucose control, this study sought to develop and test
      minimally invasive microneedles to extract dermal interstitial fluid (ISF) for
      glucose monitoring. METHODS: We used a thermal puller to fabricate individual or
      multi-needle arrays of glass microneedles with tip radii of 15-40 microm to
      penetrate 700-1,500 microm deep into the skin of anesthetized hairless rats or
      conscious, normal, adult, human subjects. After applying a vacuum of 200-500 mm
      Hg for 2-10 min, we extracted ISF and measured glucose concentration. These
      measurements were compared with glucose levels in blood collected from the tail
      vein of rats or finger stick on humans. RESULTS: Using this procedure, 1-10
      microL of ISF was extracted out of holes punctured in the skin using
      microneedles. Human subjects generally reported the procedure as painless. ISF
      glucose concentration correlated well with blood levels based on 140 measurements
      on 15 rats and six measurements on six human subjects, where 95% of rat data and
      100% of human data fell within the clinically acceptable A + B region in Clarke
      Error Grid analysis. A linear calibration factor was needed to correlate ISF and
      blood glucose concentrations using our standard procedure. Modifying the
      procedure to prevent ISF evaporation during extraction provided a one-to-one
      correlation that eliminated the need for calibration. ISF glucose measurements
      tracked rapidly changing blood glucose levels following insulin injection with a
      time lag of less than 20 min. CONCLUSIONS: These results suggest that microneedle
      devices can be used to extract ISF for painless glucose monitoring.

PMID- 15738712
TI  - Precipitation of insulin products used for continuous subcutaneous insulin
      infusion.
AB  - BACKGROUND: Commercially available insulin products used for continuous
      subcutaneous insulin infusion have been compared with respect to resistance
      towards isoelectric insulin precipitation. METHODS: The degree of isoelectric
      insulin precipitation of insulin aspart injection (IAsp), insulin lispro
      injection (ILis), and buffered human regular insulin injection (BHR) was examined
      while reducing pH through addition of diluted HCl or exposure to CO2. RESULTS:
      The pH at which defined fractions of the insulins precipitated differed among the
      three products; 10% and 90% precipitation, respectively, was observed at pH 6.41
      and pH 6.30 for ILis, pH 6.18 and pH 5.95 for BHR, and pH 5.90 and pH 5.67 for
      IAsp, in accordance with the isoelectric points of these insulin species. The
      amount of H(+)-equivalents per microliter of product to reach 10% precipitation
      was found to be highest for IAsp (5.49 nmol of H(+)-equivalents), with ILis and
      BHR almost equivalent to each other (4.46 and 4.32 nmol of H(+)-equivalents,
      respectively). Exposure to a CO2-enriched environment resulted in the same order
      of insulin precipitation of the three products as tested with HCl. CONCLUSIONS:
      Resistance towards isoelectric precipitation is highest for IAsp, lowest for
      ILis, and intermediate for BHR. Isoelectric precipitation will alter the
      pharmacokinetic properties of the insulin and could lead to occlusion of the
      infusion catheter, causing elevated blood glucose and ultimately causing diabetic
      ketoacidosis if no intervention is made. Causal relationships between the
      observed differences in resistance towards isoelectric precipitation of the
      insulin products, the mechanism behind catheter occlusion, and the clinical
      relevance of the observations require further studies.

PMID- 15738714
TI  - Biocompatibility of an electrochemical sensor for continuous glucose monitoring
      in subcutaneous tissue.
AB  - BACKGROUND: The continuous monitoring of glucose allows for tighter control of
      the glucose concentration and thus may prevent hyper- and hypoglycemia as well as
      long-term complications of diabetes. While most current systems depend on the
      transport of fluid to a glucose sensor outside the body, we investigate the
      possibility of implanting a reagent-based sensor directly into the skin. In this
      manuscript, the biocompatibility of an electrochemical sensor for continuous
      glucose monitoring was assessed in vitro and in vivo. METHODS: Cytotoxicity was
      investigated in vitro using agar diffusion testing. In vivo biocompatibility was
      assessed by means of histomorphological examination of the surrounding tissue 10
      days after sensor implantation in rats. RESULTS: The grade of cytotoxicity of the
      individual sensor components in vitro was between none and mild based on agar
      diffusion testing. The complete sensor also showed no cytotoxic effects when
      coated with the co-polymer MPC (2-methacryloyloxyethyl phosphorylcholine,
      Lipidure CM 5206, NOF Corp., Tokyo, Japan) and when assessed under working
      conditions, i.e., when a bias voltage was applied to the sensor. Additionally,
      the hydrogen peroxide-which is inherently generated by the enzymatic glucose
      detection process using glucose oxidase (GOD)-is likely to have been sufficiently
      decomposed under these working conditions. Finally, no toxic leachable substances
      were found during the cytotoxicity testing of sensors and its extracts in vitro.
      In the in vivo experiments, the strongest foreign body reaction (FBR) was found
      near the GOD-electrode using a sensor without MPC coating and without a porous
      membrane. Covering the sensor with MPC, a porous membrane, or both led to a
      gradual decrease of the FBR down to the level of the negative control.
      CONCLUSIONS: The electrochemical, reagent-based sensor with MPC coating and/or a
      porous membrane is suitable for continuous monitoring of glucose from a
      biocompatibility standpoint.

PMID- 15738713
TI  - Diffusion characteristics of microfabricated silicon nanopore membranes as
      immunoisolation membranes for use in cellular therapeutics.
AB  - OBJECTIVE: Immunoisolating membranes protect transplanted xenogeneic tissue by
      physically isolating them from the host. However, most are commercial filter
      membranes that do not possess all the features needed for immunoisolation.
      Silicon nanopore membranes are thin layers of silicon containing tens of
      thousands of nanometer-sized channels, which allow passive diffusion of small
      molecules. They are excellent size-selective barriers, and the objective of this
      study was to further characterize their immunoprotective properties and make
      comparisons with commercial filter membranes. METHODS: Diffusion across membranes
      was studied using molecules of different sizes, including fluorescein
      isothiocyanate-dextrans (relative molecular sizes of 4.4 kDa, 20 kDa, and 70
      kDa), glucose (0.18 kDa), insulin (6.1 kDa), and immunoglobulin G (IgG) (150
      kDa). Protection from complement-mediated lysis was analyzed by a hemolysis
      assay. Comparative studies were done with filter membranes that have been
      reported as immunoisolation barriers. To evaluate if silicon nanopore membranes
      changed insulin response patterns for glucose-stimulated islets, macrocapsules
      were constructed with nanopore membranes and filled with pancreatic islets, and
      dynamic perifusion studies were performed. RESULTS: Relative to commercial
      membranes, silicon nanopore membranes showed high rates of diffusion for glucose
      and insulin, and acted as efficient barriers to complement proteins and IgG. No
      other commercial membrane showed comparable diffusion and immunoisolating
      properties. Islets placed within the macrocapsule exhibited glucose-responsive
      insulin secretion in perifusion studies. CONCLUSIONS: Silicon nanopore membranes
      possess unique and desirable diffusion properties as immunoisolation membranes
      and allow rapid response times for the stimulation of islets by glucose. These
      features are attributed to the physical properties of the membranes, namely, the
      straight channels, adequate porosity, and the 5 microm thickness.

PMID- 15738715
TI  - Noninvasive and minimally invasive methods for transdermal glucose monitoring.
AB  - Noninvasive and minimally invasive techniques for monitoring glucose via the skin
      are reviewed. These approaches rely either on the interaction of electromagnetic
      radiation with the tissue or on the extraction of fluid across the barrier. The
      structure and physiology of the skin make the technical realization of
      transdermal glucose monitoring a difficult challenge. The techniques involving
      transdermal fluid extraction circumvent and/or compromise the barrier function of
      skin's outermost and least permeable layer, the stratum corneum, by the
      application of physical energy. While sonophoresis and microporation methods, for
      example, are in relatively early-stage development, a device using reverse
      iontophoresis [the GlucoWatch Biographer (Cygnus, Inc., Redwood City, CA)] is
      already commercially available. Optical techniques to monitor glucose are truly
      noninvasive. The tissue is irradiated, the absorbed or scattered radiation is
      analyzed, and the information is processed, to provide a measure proportional to
      the concentration of glucose in the dermal tissue. These techniques include near
      infrared and Raman spectroscopy, polarimetry, light scattering, and photoacoustic
      spectroscopy. By contrast, impedance spectroscopy measures changes in the
      dielectric properties of the tissue induced by blood glucose variation. Large
      scale studies in support of efficacy of these methodologies are as yet
      unavailable. At present, therefore, transdermal fluid extraction technologies are
      offering greater promise in terms of practical and realizable devices for patient
      use. The truly noninvasive allure of the optical approach assures continued and
      intense research activity--for the moment, however, an affordable, efficient, and
      portable system is not on the immediate horizon.

PMID- 15738716
TI  - A national progress report on diabetes: successes and challenges.
AB  - Over the last few decades, numerous public health agencies and other private and
      public organizations have sought to prevent and delay the disabling complications
      of diabetes by increasing the use of preventive care practices and reducing risk
      factors for complications among people with diabetes. Now, federal diabetes
      surveillance activities are yielding encouraging reports that progress is being
      made in increasing the use of preventive care practices, reducing risk factors
      for complications, and preventing or delaying diabetes complications. However,
      although several gains have been noted, levels of preventive care practices
      remain suboptimal, risk factors for diabetes complications are too prevalent, and
      diabetes complications are too pervasive. Furthermore, with compelling evidence
      that the onset of diabetes can be prevented or delayed among adults at high risk,
      prevention of diabetes has become a major new challenge. Additional efforts are
      needed to address the growing problems of obesity and physical inactivity, to
      identify the most efficacious and cost-effective prevention strategies and
      interventions, and to implement surveillance activities that allow us to gauge
      our success. Although progress has been made against diabetes complications, the
      current epidemic of diabetes increases the urgency of primary prevention efforts.

PMID- 15738717
TI  - Loss of defense against stress: diabetes and heat shock proteins.

PMID- 15738718
TI  - Data for management of diabetes in primary care--master or minion?

PMID- 15738719
TI  - The development of minimally invasive continuous Metabolic Monitoring
      Technologies in the U.S. Army TMM Research Program.
AB  - The Technologies for Metabolic Monitoring and Julia Weaver Fund Research Program
      (TMM) promotes the development of minimally invasive, innovative technologies for
      the monitoring and assessment of metabolic changes that are important to the
      management of diabetes. This program also promotes the advancement of biological
      monitoring technologies for healthy individuals operating in extreme
      environments, such as soldiers and astronauts. These technologies have focused on
      measurements of analytes in interstitial fluids and functional outcomes related
      to glucose regulation. TMM investigators have advanced new sensing methods and
      are working to overcome technological barriers to long-term implants. This paper
      reviews the current goals, research areas, and future direction of the program.

PMID- 15738720
TI  - Diabetes and the World Wide Web.
AB  - The World Wide Web has become remarkably quickly an alternative source of
      information for patients and their relatives, as well as students and health-care
      professionals. A whole plethora of websites and Internet-based applications
      related to diabetes have appeared in recent years. In this column, selected
      issues surrounding the use of such websites are considered and the need for more
      evaluation of such diabetes sites, as well as the Internet medium itself, is
      highlighted.

PMID- 15738721
TI  - Function of the GlucoWatch G2 Biographer during exercise.

PMID- 15738723
TI  - Colorectal cancer: preventable, treatable, and beatable!

PMID- 15738724
TI  - Psychological well-being and symptoms in women with chronic constipation treated
      with sodium picosulphate.
AB  - The use of sodium picosulphate has been restricted to a few weeks due to its
      potentially harmful effect on the colon. In spite of this restriction, however,
      many patients prefer this pharmaceutical drug. The authors have earlier studied
      the use of sodium picosulphate and found regular use leads to a moderate dose
      escalation. The aim of this study was to examine whether subjects who use
      laxatives containing sodium picosulphate differ in their psychological well-being
      and symptoms from subjects who use other laxatives, and to decide, on the basis
      of the results, how to use drugs containing sodium picosulphate. Eighty-six
      women, age 27-65 years, with chronic constipation were interviewed by two self
      administered questionnaires: the Psychological General Well-Being Index (PGWB)
      and the Gastrointestinal Symptom Rating Scale (GSRS). Twenty-two of the subjects
      were interviewed a second time some months later after inclusion in a drug trial.
      Thirty-five women used sodium picosulphate regularly every week and 51 used other
      laxatives. Psychological well-being according to the PGWB was better for the
      subjects who used sodium picosulphate regularly than for those who used other
      laxatives (97 compared to 86, p, .017) This difference was due to less anxiety
      (p, .0001). There was no difference between the groups according to the GSRS.
      After inclusion in a drug trial, but before the introduction of the drugs, the
      group who did not use sodium picosulphate was remarkably improved with less
      anxiety, better self-control, and reduced abdominal pain and constipation. As the
      psychological well-being was better for the subjects who used sodium
      picosulphate, these drugs can be used when patients fail to respond to
      traditional therapies.

PMID- 15738727
TI  - Living with a colicky infant.
AB  - Infant colic is prolonged hard crying for no apparent reason in an otherwise
      healthy infant. The purpose of this study was to describe the parents'
      experiences of caring for their infants with colic. This qualitative study
      employed a multiple case study design using a descriptive approach through
      indepth interviews. Five of the interviews were conducted in person, and 10 were
      conducted via e-mail. One or both parents of 15 colicky infants were interviewed
      about their recent experiences of living with colicky infants. Three themes-
      crying, emotions (anger, frustration, worry, and guilt), and feelings (hopeless,
      helpless, isolated, and unloved) were identified. This study adds the rich
      description that was missing from the previous two qualitative studies of infant
      colic. It also adds fathers' perspectives of the experience of living with a
      colicky infant. Lastly, this study demonstrates that indepth interviews can be
      conducted via e-mail as well as in person.

PMID- 15738725
TI  - Primary sclerosing cholangitis: a case presentation.
AB  - Liver function tests are elevated in a variety of settings and with a mild
      elevation, it is difficult to decipher the cause. Typical causes of elevated
      liver enzymes may range from hepatocellular injury such as hepatitis C, to
      obstructive causes, such as primary sclerosing cholangitis. Primary sclerosing
      cholangitis is known to be associated with inflammatory bowel disease and may be
      more common than once thought.This article presents case study of a patient who
      presented with mildly elevated liver function tests and intermittent diarrhea.
      The patient was diagnosed with Crohn's disease and primary sclerosing
      cholangitis. The patient's presentation and the relation of inflammatory bowel
      disease and primary sclerosing cholangitis will be discussed. The importance of
      early detection of primary sclerosing cholangitis in an effort to decrease the
      morbidity and mortality from cholangiocarcinoma will also be emphasized. An
      overview of various diagnostic testing needed to make the diagnosis, as well as
      treatment modalities of both Crohn's disease and primary sclerosing cholangitis
      will also be presented.

PMID- 15738729
TI  - The stool DNA test: an emerging technology in colorectal cancer screening.
AB  - The stool DNA test is considered an emerging technology in screening for
      colorectal cancer. The stool DNA test detects DNA markers which are shed from
      cells of premalignant adenomas and cancers into the stool. Potentially, both
      preclinical and clinical colorectal cancer may be detected. Panels of multiple
      DNA markers are used to ensure a high sensitivity for colorectal cancer. In this
      article, several advantages of the stool DNA test (compared with current
      colorectal cancer screening methods) are discussed. The stool DNA test may be
      more patient-friendly and has a higher degree of sensitivity and specificity for
      colorectal cancer. No bowel or dietary preparation is required and the test is
      noninvasive. The stool DNA test screens the entire colon and may detect some
      other types of cancers proximal to the colon. In the future, there may be
      potential to use the stool DNA test to screen for aerodigestive cancers (lung,
      esophageal, gastric, and pancreatic), in addition to colorectal cancer. An
      improved noninvasive screening test would help allocate colonoscopy resources to
      those patients who would benefit the most. Colorectal cancer screening cost
      effectiveness may also be improved. Some limitations of the stool DNA test
      include the need for clinical studies in average-risk populations and marker
      refinement. An automated testing system may help reduce costs and turnaround
      times. Despite recognized limitations, the stool DNA test is a promising new
      diagnostic tool with the potential to improve effectiveness of colorectal cancer
      screening.

PMID- 15738730
TI  - Establishing an Australian nurse practitioner-led colorectal cancer screening
      clinic.
AB  - In Australia, colorectal cancer is the most commonly occurring internal cancer
      affecting both men and women, and the second most common cause of cancer-related
      death. Flexible sigmoidoscopy has not been commonly used as a screening tool in
      Australia due primarily to lack of resources. Until now, people at average risk
      of developing bowel cancer frequently undergo colonoscopy after referral to a
      specialist. To fill an identified need, a nurse practitioner-led colorectal
      screening service providing fecal occult blood testing and flexible
      sigmoidoscopy, health education and promotion, patient counseling, information
      and a referral point for general practitioners, and a referral service for above
      average-risk patients was established in a South Australian metropolitan teaching
      hospital. Establishment of this clinic required advanced and extended theoretical
      and clinical preparation for the nurse practitioner, as well as development of
      interdisciplinary relationships, referral processes, clinical infrastructure, and
      a marketing strategy. An audit of the first 100 flexible sigmoidoscopy patients
      revealed service and procedural outcomes that compared favorably with other
      colorectal screening services as well as a high level of patient satisfaction.

PMID- 15738731
TI  - Staffing issues in the gastroenterology setting.

PMID- 15738732
TI  - Recommended care and handling of flexible endoscopes: endoscope storage.

PMID- 15738733
TI  - The inspiring leader.

PMID- 15738734
TI  - A literature review of fecal impaction.

PMID- 15738735
TI  - Specialty nomenclature: a worthwhile challenge.

PMID- 15738736
TI  - Development of the Society of Gastroenterology Nurses and Associates Minimum Data
      Set: an evidence-based resource.
AB  - The Society for Gastroenterology Nurses and Associates (SGNA) has developed a
      Minimum Data Set identifying the essential elements necessary to document
      delivery of patient care in the gastrointestinal endoscopic setting. Standardized
      information, such as a minimum data set, for facilitating communication among
      practitioners is believed to enhance patient outcomes. The SGNA Minimum Data Set
      was developed for "public" use to facilitate quality patient outcomes and to
      enhance the education, research, and clinical practice of GI nurses. Data were
      collected from a cross-sectional representation of geographic locations and
      settings (major medical centers, community hospitals, and free-standing clinics)
      in order to establish a broad evidence-based perspective for the data set. Data
      for the four primary endoscopic procedures: esophagogastroduodenoscopy (EGD),
      colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and flexible
      sigmoidoscopy; as well as the most common therapeutic procedures (biopsy,
      polypectomy, dilation, endoscopic ultrasound [EUS], and manometry/motility) were
      analyzed to establish the key elements of the Minimum Data Set. Focus groups with
      members from around the U.S. verified the validity of the Minimum Data Set. The
      SGNA Minimum Data Set can be used by healthcare institutions, industry, and
      individuals to facilitate the capture and analysis of standardized data for the
      purpose of improving GI patient outcomes and enhancing delivery of nursing care.

PMID- 15738737
TI  - Use of the SGNA Minimum Data Set in the clinical area.

PMID- 15738738
TI  - Transitioning from paper to computerized documentation.
AB  - Although charting forms have evolved over time to meet the changing needs in
      healthcare, little has changed in the process of documentation until the
      introduction of computers in healthcare in the late 20th century. The author
      describes three early nursing documentation systems and the evolution of the
      automated process. One of the important lessons learned about the move from paper
      to computerized charting is that the process is not "automatic."

PMID- 15738740
TI  - Is it time to replace the Hamilton Depression Rating Scale as the primary outcome
      measure in treatment studies of depression?

PMID- 15738741
TI  - Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic
      patients treated with risperidone.
AB  - Structural neuroimaging techniques have consistently shown that treatment of
      schizophrenic patients with conventional antipsychotics causes an increase in
      basal ganglia volume. However, findings in schizophrenic patients treated with
      the newer atypical antipsychotic drugs are less consistently reported. To explore
      this issue, the authors used a whole-brain, unbiased, and automated technique for
      comparing brain structural features across scans in schizophrenic patients before
      and after a treatment with the atypical antipsychotic risperidone. T1-weighted
      images from 11 first-episode neuroleptic-naive schizophrenic patients were
      processed and analyzed for regions of interest (basal ganglia) by using optimized
      voxel-based morphometry. Scans were repeated after 3 months of continuous
      treatment with risperidone. Region of interest-based voxel-based morphometry
      analyses revealed increases in gray matter volume for the right and left caudate
      nuclei and for the left accumbens after the treatment with risperidone. Hence, in
      our sample of schizophrenic patients, treatment with risperidone was associated,
      in contrast to the findings for other atypical antipsychotics, with an increase
      in basal ganglia volume. Such discrepancy could be related to the
      pharmacodynamics of risperidone (the atypical antipsychotic showing the higher
      affinity for D2 receptors) and the rather high mean doses used in our study (ie,
      6.05 mg/d).

PMID- 15738742
TI  - Suboptimal antidepressant use in the elderly.
AB  - Ongoing changes in available agents and health care delivery systems have made it
      imperative to study the quality of antidepressant use in vulnerable and
      traditionally underserved elderly. We conducted a retrospective cohort study
      among 12,130 new antidepressant users aged > or =65 years with a recent diagnosis
      of depression in the Pennsylvania Pharmaceutical Assistance Contract for the
      Elderly Program from January 1, 1994, to December 31, 1999. Additional use
      information was available through Medicare data. Potentially hazardous
      antidepressant regimens were defined as use of highly anticholinergic agents or
      daily dosages in excess of geriatric prescribing guidelines. Low-intensity
      regimens were defined by lower than recommended daily dosages, too-short
      durations of therapy, or lack of follow-up. Of all elderly antidepressant users,
      43.3% were taking suboptimal regimens. Potentially hazardous regimens were used
      by 11.9%, including 7.3% taking highly anticholinergic agents and 5.3% using
      excessively high daily dosages. Low-intensity regimens were used by 34.8% of
      patients, including 7.6% with excessively low daily dosages, 19.3% with short
      durations of therapy, and 14.8% with inadequate follow-up. Potentially hazardous
      regimens were associated with ages 65 to 74 years, nursing home residence, cancer
      diagnoses, less comorbidity, use of other psychiatric medications, making more
      physician visits, and earlier calendar years. Low-intensity regimens were
      associated with ages > or =85 years, nonwhite race, greater comorbidity, fewer
      physician visits or inpatient days in the baseline 6 months, and not using other
      psychiatric medications. Suboptimal antidepressant use remains common in the
      elderly, especially the use of inadequately intensive regimens. Interventions are
      needed to improve the quality and outcomes of antidepressant use in this
      vulnerable population.

PMID- 15738743
TI  - Orphan comparisons and indirect meta-analysis: a case study on antidepressant
      efficacy in dysthymia comparing tricyclic antidepressants, selective serotonin
      reuptake inhibitors, and monoamine oxidase inhibitors by using general linear
      models.
AB  - Direct comparisons of the efficacy of competing interventions are not always
      available in the literature. This situation leads to the presence of clinically
      relevant "orphan comparisons" of therapeutic interventions which have never been
      compared head-to-head. To overcome this limitation, simple methods for indirect
      meta-analysis have been suggested. Nevertheless, their results are prone to bias
      when more than 1 indirect comparison is tested because of the likely duplication
      of data for some comparisons. In contrast, general linear models can be used to
      extend simple indirect meta-analysis beyond 1 indirect comparison by fitting to
      incomplete data using maximum likelihood within the framework of multitreatment
      comparisons. This study presents a tutorial application of general linear models
      to the comparative efficacy of several antidepressants in dysthymia (tricyclic
      antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase
      inhibitors. Working with previously published data comparing the efficacy of
      antidepressants with placebo, it is shown that tricyclic antidepressants and
      selective serotonin reuptake inhibitors present similar efficacy (odds ratio =
      1.19, P = 0.37; relative risk = 1.10, P = 0.24; risk difference = 0.03, P =
      0.53), whereas monoamine oxidase inhibitors outperform both tricyclic
      antidepressants and selective serotonin reuptake inhibitors, at least for some
      effect scales (odds ratio = 1.57, P = 0.05; relative risk = 1.25, P = 0.05; risk
      difference = 0.09, P = 0.08). This finding, which is an instance of a relevant
      orphan comparison and could not be obtained otherwise, could motivate the conduct
      of clinical trials or focused systematic reviews to support or refute its
      importance through appropriate head-to-head comparisons.

PMID- 15738744
TI  - Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and
      norepinephrine.
AB  - This analysis assessed the effects of duloxetine, a dual reuptake inhibitor of
      serotonin and norepinephrine, on indices of cardiovascular safety, including
      heart rate, blood pressure (BP), and electrocardiograms (ECGs), in a large group
      of clinical trial patients with depression. Data were available from 8 double
      blind, randomized, placebo-controlled (n = 777), and active comparator-controlled
      depression trials. Duloxetine (n = 1139) doses ranged from 40 to 120 mg/d, and
      fluoxetine (n = 70) and paroxetine (n = 359) were administered at a dose of 20
      mg/d. Patients were treated for 8 to 9 weeks. There was a significant increase
      for duloxetine compared with placebo for heart rate (1.6 vs. -0.6 beats per
      minute) and for systolic BP (1.0 vs. -1.2 mm Hg); the difference for diastolic BP
      (1.1 vs. 0.3) was not significant. There were no significant differences between
      duloxetine and placebo treatment groups in the incidence of sustained (at least 3
      consecutive visits) elevations in systolic (duloxetine 1.0%, placebo 0.4%),
      diastolic (duloxetine 0.4%, placebo 0.4%), or either (duloxetine 1.3%, placebo
      0.8%) BP. Moreover, the effect of duloxetine on mean changes in supine systolic
      and diastolic BP was not significantly different from that of fluoxetine or
      paroxetine. Drug-placebo differences in mean changes in electrocardiograms (eg,
      QTc, PR, and QRS intervals) were neither statistically nor clinically
      significant, with the exception that duloxetine 120 mg/d had significant
      decreases in PR and QRS intervals compared with placebo. These data demonstrate
      that duloxetine has modest effects on heart rate and BP and no clinically
      meaningful effect on electrocardiogram profiles in a relatively healthy cohort of
      clinical trial patients. The cardiovascular effects of duloxetine appear to be
      comparable with medications considered to be first-line options for depression.

PMID- 15738745
TI  - A meta-analytic review of the efficacy of drug treatment in generalized anxiety
      disorder.
AB  - A meta-analytic review of the efficacy of pharmacological treatment in
      generalized anxiety disorder was conducted. The main substance classes were
      compared: benzodiazepines and azapirones. The impact of methodological variables
      was investigated such as sample size and use of a placebo run-in. After a
      comprehensive literature search to May 2002 (via databases, hand search,
      secondary sources, internet, contact of researchers, and pharmaceutical
      companies), the results of 48 studies were integrated. Weighted Hedges g was
      computed and a random-effects analysis was done. Effect sizes were computed for
      anxiety, depression, and clinical significance. Sensitivity analyses were
      conducted. Pharmacotherapy was superior to placebo in all symptom categories.
      Azapirones and benzodiazepines were equally effective. Compliance (as measured by
      dropout rate) was higher for benzodiazepines. Only sample size was significantly
      associated with effect size. Pharmacotherapy, especially benzodiazepines and
      azapirones, is effective in the short-term treatment of patients with generalized
      anxiety disorder. There was no superiority of 1 drug class in reducing
      symptomatology.

PMID- 15738746
TI  - Efficacy of pregabalin in the treatment of generalized anxiety disorder: double
      blind, placebo-controlled comparison of BID versus TID dosing.
AB  - Pregabalin is a new anxiolytic that acts as a presynaptic inhibitor of the
      release of excessive levels of excitatory neurotransmitters by selectively
      binding to the alpha2-delta subunit of voltage-gated calcium channels. The
      current study evaluated the anxiolytic efficacy of BID versus TID dosing of
      pregabalin in patients with generalized anxiety disorder. Outpatients with
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition generalized
      anxiety disorder and having baseline Hamilton Anxiety (HAM-A) total scores > or
      =20 were randomized to 6 weeks of double-blind treatment with pregabalin 200 mg/d
      (BID; N = 78), 400 mg/d (BID; N = 89), or 450 mg/d (TID; N = 88) or placebo (N =
      86). Mean improvement in HAM-A total score at last observation carried forward
      end point was significantly greater on pregabalin 200 (P = 0.006), 400 (P =
      0.001), and 450 mg/d (P = 0.005) compared with placebo. Pairwise comparisons of
      BID versus TID dosing found no difference in HAM-A change score at end point. All
      3 pregabalin dosage groups showed significantly greater efficacy versus placebo
      at end point on the HAM-A psychic and somatic anxiety factor scores. Improvement
      on both factors was rapid: significance versus placebo was achieved as early as
      the first assessment at week 1, with > or =30% reduction in HAM-A severity and
      equal or greater improvement for every subsequent visit in > or =38% of patients
      in all 3 pregabalin dosage groups (P < or = 0.001). Pregabalin was well
      tolerated, and despite the fixed-dose study design, discontinuations caused by
      adverse events ranged from 9% to 13%--comparable with that observed with placebo
      (8%). This study demonstrates that pregabalin is an effective treatment of
      generalized anxiety disorder, with BID dosing showing similar efficacy and
      comparable tolerability with TID dosing.

PMID- 15738747
TI  - Neuropsychological test performance in healthy elderly volunteers before and
      after donepezil administration: a randomized, controlled study.
AB  - Neuropsychological performance was examined in healthy elderly participants
      administered the cholinesterase inhibitor donepezil. Of principal interest was
      examination of the sensitivity of a series of neuropsychological measures to
      detect cognitive changes after drug administration using typical phase I research
      parameters (eg, a small sample over a short treatment period). In this double
      blind parallel study over a period of 6 weeks, 26 healthy elderly participants
      (aged 55 to 75 years) were randomized into 1 of 2 arms (14 donepezil and 12
      placebo) and completed 14 days of donepezil (5 mg, twice a day) or placebo (twice
      a day). A battery of neuropsychological tests was administered on days 0, 14
      (prerandomization), 28 (end of treatment), and 42 (washout). After 2 weeks of
      donepezil treatment (day 28), subjects in the donepezil group performed slightly
      but significantly worse on 2 tests of speed, attention, and short-term memory (P
      < 0.05) compared with the placebo group. No significant improvement in
      performance was present on any test during treatment with donepezil. These
      results are consistent with a previous study in healthy young participants in
      which transient mild worsening on some cognitive tests during donepezil
      administration was observed, possibly caused by perturbation of an already
      optimized cholinergic system in healthy participants. These results are important
      to consider when designing clinical development plans for putative cognitive
      enhancing drugs; in addition, these results raise questions about when the
      optimal point to begin treatment is for patients who have not yet met criteria
      for dementia.

PMID- 15738748
TI  - Maintenance therapy with fluoxetine in posttraumatic stress disorder: a placebo
      controlled discontinuation study.
AB  - The effect of fluoxetine (FLU) in posttraumatic stress disorder was studied in a
      one-year trial. Subjects received open-label treatment for 6 months, followed by
      double-blind randomized treatment with FLU or placebo (PBO) for 6 months. Rates
      of relapse were compared using the Clinical Global Impressions of Improvement.
      One hundred twenty-three subjects entered open-label treatment, of whom 114
      returned at least once. Sixty-two subjects were randomized to receive FLU or PBO,
      of whom 57 returned at least once and were analyzed. The dose of FLU ranged from
      10 to 60 mg/d; at randomization, mean doses were 48.6 and 42.1 mg for FLU and PBO
      groups. Rates of relapse were 22% for FLU versus 50% for PBO (P = 0.02), and time
      to relapse on FLU was longer than for PBO (P = 0.02, log-rank statistic). The
      odds ratio for relapse on PBO relative to FLU was 3.50. No significant
      differences were found on other measures. Fluoxetine was well tolerated during
      double-blind treatment.

PMID- 15738749
TI  - Low-dose fluvoxamine as an adjunct to reduce olanzapine therapeutic dose
      requirements: a prospective dose-adjusted drug interaction strategy.
AB  - Despite the advances in antipsychotic pharmacotherapy over the past decade, many
      atypical antipsychotic agents are not readily accessible by patients with major
      psychosis or in developing countries where the acquisition costs may be
      prohibitive. Olanzapine is an efficacious and widely prescribed atypical
      antipsychotic agent. In theory, olanzapine therapeutic dose requirement may be
      reduced during concurrent treatment with inhibitors of drug metabolism. In vitro
      studies suggest that smoking-inducible cytochrome P450 (CYP) 1A2 contributes to
      formation of the metabolite 4'-N-desmethylolanzapine. The present prospective
      study tested the hypothesis that olanzapine steady-state doses can be
      significantly decreased by coadministration of a low subclinical dose of
      fluvoxamine, a potent inhibitor of cytochrome P450 1A2. The study design followed
      a targeted "at-risk" population approach with a focus on smokers who were likely
      to exhibit increased cytochrome P450 1A2 expression. Patients with stable
      psychotic illness (N = 10 men, all smokers) and receiving chronic olanzapine
      treatment were evaluated for steady-state plasma concentrations of olanzapine and
      4'-N-desmethylolanzapine. Subsequently, olanzapine dose was reduced from 17.5 +/-
      4.2 mg/d (mean +/- SD) to 13.0 +/- 3.3 mg/d, and a nontherapeutic dose of
      fluvoxamine (25 mg/d, PO) was added to regimen. Patients were reevaluated at 2,
      4, and 6 weeks during olanzapine-fluvoxamine cotreatment. There was no
      significant change in olanzapine plasma concentration, antipsychotic response, or
      metabolic indices (eg, serum glucose and lipids) after dose reduction in the
      presence of fluvoxamine (P > 0.05). 4'-N-desmethylolanzapine/olanzapine metabolic
      ratio decreased from 0.45 +/- 0.20 at baseline to 0.25 +/- 0.11 at week 6,
      suggesting inhibition of the cytochrome P450 1A2-mediated olanzapine 4'-N
      demethylation by fluvoxamine (P < 0.05). In conclusion, this prospective pilot
      study suggests that a 26% reduction in olanzapine therapeutic dose requirement
      may be achieved by coadministration of a nontherapeutic oral dose of fluvoxamine.

PMID- 15738750
TI  - Does modafinil enhance cognitive performance in young volunteers who are not
      sleep-deprived?
AB  - In a double-blind, parallel groups study, 60 healthy student volunteers (29 men
      and 31 women, aged 19-22 years) were randomly allocated to receive placebo, 100
      or 200 mg modafinil. Two hours later, in the early evening, they completed an
      extensive cognitive battery. The 3 groups did not differ in self-ratings of
      sleepiness or tiredness before the testing session, and there were no treatment
      associated changes in these or in mood ratings during the tests. Modafinil was
      without effect in several tests of reaction time and attention, but the 200-mg
      group was faster at simple color naming of dots and performed better than placebo
      in the Rapid Visual Information Processing test of sustained attention. Modafinil
      was without effect on spatial working memory, but the 100-mg group performed
      better in the backward part of the digit span test. Modafinil was without effect
      on verbal short-term memory (story recall), but 100 mg improved digit span
      forward, and both doses improved pattern recognition, although this was
      accompanied by a slowing of response latency in the 200-mg group. There were no
      significant effects of modafinil compared with placebo in tests of long-term
      memory, executive function, visuospatial and constructional ability, or category
      fluency. These results suggest that the benefits of modafinil are not clearly
      dose-related, and those from 100 mg are limited to the span of immediate verbal
      recall and short-term visual recognition memory, which is insufficient for it to
      be considered as a cognitive enhancer in non-sleep-deprived individuals.

PMID- 15738751
TI  - Maintenance treatment of severe tardive dyskinesia with clozapine: 5 years'
      follow-up.
AB  - ?Drug-induced tardive dyskinesia (TD) affects approximately 20% to 30% of
      schizophrenic patients. Although it is usually mild, from 1% to 8% of patients
      may develop severe TD. Second-generation antipsychotics have demonstrated a lower
      risk of inducing TD. However, despite the advances brought by second-generation
      antipsychotics, the treatment strategies for TD remain problematic, given both
      the lack of an established therapeutic choice and the need for long-term use of
      antipsychotics in the treatment of schizophrenia. Clozapine is an atypical
      antipsychotic with minimal risk of inducing TD. Furthermore, it has been
      suggested that clozapine might actually improve the symptoms of TD. Accordingly,
      we evaluated the effects of clozapine on severe TD over 5 years. Seven patients
      meeting Diagnostic and Statistical Manual of Mental Disorders, Revised Third
      Edition criteria for chronic exacerbated schizophrenia (mean age 28.5 +/- 10.2
      years) and presenting severe TD, defined as Abnormal Involuntary Movements Scale
      score above 13, were treated with clozapine and followed up for 5 years.
      Extrapyramidal Symptoms Rating Scale assessment was performed in all patients at
      baseline, after 6 months and 3 and 5 years. Mean Extrapyramidal Symptoms Rating
      Scale scores decreased 83% after 3 years and 87.5% after 5 years. Mean dose for
      all patients was 428 +/- 269 mg/d after 5 years. Results from this open-label
      study suggest that clozapine may be a further option for the treatment of TD over
      long term.

PMID- 15738752
TI  - Olanzapine-induced hyperglycemia: role of humoral insulin resistance-inducing
      factors.

PMID- 15738753
TI  - Rechallenge of late-onset neutropenia with clozapine.

PMID- 15738754
TI  - High dose of multiple neuroleptic treatments for schizophrenia in Japan: dose
      reduction and electrocardiographic changes.

PMID- 15738756
TI  - Tadalafil in a patient with treatment-resistant depression and antidepressant
      polypharmacy.

PMID- 15738755
TI  - The association between cytochrome P450 2D6 genotype and prescription patterns of
      antipsychotic and antidepressant drugs in hospitalized psychiatric patients: a
      retrospective follow-up study.

PMID- 15738757
TI  - The efficacy of fluoxetine and a stop-start technique in the treatment of
      premature ejaculation and anxiety.

PMID- 15738758
TI  - Increased libido with the combined use of venlafaxine and mirtazapine.

PMID- 15738759
TI  - Hypomania with topiramate.

PMID- 15738760
TI  - Mortality follow-up of patients since commencing lithium therapy.

PMID- 15738761
TI  - Effectiveness of herbal medicine (kampo) and changes of quality of life in
      patients with somatoform disorders.

PMID- 15738773
TI  - The mannequin sign.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVES: The critical appraisal
      of the mannequin sign in the validation of patients with symptoms of sciatica.
      SUMMARY OF BACKGROUND DATA: Sixty-five consecutive patients with magnetic
      resonance imaging-proven lumbar disc herniation and symptoms of sciatica. Mean
      patient age was 48 (range 28-62) years. Thirty-seven patients were male and 28
      were female. METHODS: The mannequin sign is positive when a patient adopts an
      antalgic posture with the relevant lower limb flexed at the hip and knee with the
      pelvis tilting towards the affected side, in the classic manner of a mannequin's
      pose. Reproducibility of the sign was recorded when all patients were examined by
      a second clinician. Lumbar disc herniation with nerve root impingement was
      confirmed by magnetic resonance imaging. RESULTS: The mannequin sign had 100%
      reproducibility and 80% sensitivity in diagnosing lumbar disc herniations with
      nerve root impingement. Twenty-four patients had L4-L5 disc herniations and 41
      had L5-S1 disc herniations. CONCLUSION: Astute clinical examination can minimize
      inaccurate diagnosis, unnecessary investigations, and even inappropriate surgical
      intervention. The mannequin sign, first observed and anecdotally reported by the
      senior author (D.C.), has now been critically appraised.

PMID- 15738772
TI  - The surgical treatment of the lumbar disc prolapse: nucleotomy with additional
      transpedicular dynamic stabilization versus nucleotomy alone.
AB  - STUDY DESIGN: Clinical and radiologic study evaluating the outcome after
      nucleotomy with dynamic stabilization compared with nucleotomy alone. OBJECTIVES:
      To investigate the effect of dynamic stabilization on the progression of
      segmental degeneration after nucleotomy. SUMMARY OF BACKGROUND DATA: Nucleotomy
      as treatment for lumbar disc prolapse in combination with initial segment
      degeneration may lead to segmental instability. Dynamic stabilization systems
      restrict segmental motion and thus prevent further degeneration of the lumbar
      spine. They are designed to avoid the disadvantages of rigid fixation, such as
      pseudarthrosis and adjacent segment degeneration. METHODS: Eighty-four patients
      underwent nucleotomy of the lumbar spine for the treatment of symptomatic disc
      prolapse. Additional dynamic stabilization (DYNESYS) was performed in 35 of those
      cases. All patients showed signs of initial disc degeneration (MODIC I). They
      underwent evaluation before surgery, 3 months after surgery, and at follow-up.
      The mean duration of follow-up was 34 months. Examinations included radiographs,
      magnetic resonance imaging (MRI), physical examination, and subjective patient
      evaluation using Oswestry score and visual analog scale (VAS). RESULTS: Clinical
      symptoms, Oswestry score, and VAS improved significantly in both groups after 3
      months. At follow-up, a significant increase in the Oswestry score and in the VAS
      was seen only in the nonstabilized group. In the dynamically stabilized group, no
      progression of disc degeneration was noted at follow-up, whereas radiologic signs
      of accelerated segmental degeneration existed in the solely nucleotomized group.
      There were no implant-associated complications. CONCLUSIONS: The applied dynamic
      stabilization system is useful to prevent progression of initial degenerative
      disc disease of lumbar spinal segments after nucleotomy.

PMID- 15738774
TI  - Clinical measurements of cement injection pressure during vertebroplasty.
AB  - STUDY DESIGN: Clinical study of injection pressure during vertebroplasty.
      OBJECTIVES: To investigate the range of injection pressures during conventional
      vertebroplasty interventions and to study the influence of syringe design and
      cement polymerization time on injection pressure. SUMMARY OF BACKGROUND DATA:
      Vertebroplasty is an efficient procedure for the treatment of painful vertebral
      fractures. However, cement leakage is a potentially serious complication.
      Although injection pressure has been suggested as a factor for extravasation
      risk, to date, there are only anecdotal reports of pressure data for cement
      augmentation in the clinic. METHODS: Using a syringe holder instrumented with
      load and displacement transducers, injection pressure and volume were recorded in
      vivo during conventional cement augmentation. Wide (3 mm opening) and normal (1.8
      mm opening) syringes were alternated such that each type was evaluated for early
      (300-500 seconds postmixing) and late (>500 seconds postmixing) cement
      polymerization time. The influence of syringe type and polymerization time on
      injection pressure was evaluated using a multifactorial analysis of variance
      followed by Scheffe post hoc comparison. RESULTS: The maximum peak injection
      pressure measured was 3215 kPa. The average pressure peaks for normal and wide
      syringes were 1693 +/- 653 kPa and 1727 +/- 597 kPa, respectively. No
      statistically significant differences were found between injection pressures with
      wide and normal syringes. Higher injection pressures were observed later in the
      polymerization process. CONCLUSIONS: High injection pressures approaching 20
      atmospheres are reached during conventional vertebroplasty. Widening the syringe
      tip diameter did not significantly change injection pressures, whereas elapsed
      time did. Further research is needed to improve injection equipment and materials
      for vertebroplasty.

PMID- 15738775
TI  - Validation of the Korean version of the oswestry disability index.
AB  - STUDY DESIGN: Validation of a translated, culturally adapted questionnaire.
      OBJECTIVES: To translate and culturally adapt a Korean version of the Oswestry
      Disability Index (ODI) and to validate its use in Korean patients. SUMMARY OF
      BACKGROUND DATA: The ODI is one of the most widely used and validated instruments
      for measuring disability in spinal disorders. However, no validated Korean
      version of the index was available at the time our study was initiated. METHODS:
      The study was carried out in three phases: the first was translation into Korean
      and cultural adaptation of the questionnaire; the second was a pilot study to
      assess the comprehensibility of the prefinal version and modification; the third
      was a reliability and validity study of the final version. The Korean version was
      tested on 206 patients with lumbar spinal disorders who had undergone operations
      at the authors' institute. Test-retest reliability, internal consistency,
      concurrent validity, and construct validity were investigated. Follow-up
      questionnaires were obtained from 39 patients at the 3-month postoperative follow
      up meeting. Differences in the ODI, visual analog scale (VAS), and World Health
      Organization (WHO) quality of life assessment (WHOQOL-BREF) between preoperative
      and follow-up questionnaires were evaluated. The correlation of the postoperative
      ODI with the pain rating on a visual analog scale and WHOQOL-BREF was also
      analyzed. RESULTS: Test-retest reliability was assessed with 88 patients in a
      time interval of 48 hours. The intraclass correlation coefficient of test-retest
      reliability was 0.9167. Reliability estimated by the internal consistency reached
      a Cronbach's alpha of 0.84. The correlation of the preoperative ODI with the pain
      rating on a visual analog scale (100 mm) was r = 0.425 (P = 0.0001). The
      correlation between three of the WHOQOL-BREF domains (physical health,
      psychological health, and environment) and the ODI was statistically significant.
      The correlation coefficient between the ODI and physical health domain of the
      WHOQOL-BREF was r = -0.48 (P < 0.05). The correlations with psychological health
      and environment domains were low with r = -0.192 and -0.160, respectively, even
      though statistically significant (P < 0.05). The correlation of the postoperative
      ODI with the pain rating on a visual analog scale (100 mm) was r = 0.626 (P =
      0.0001). The correlation between all four domains of the WHOQOL-BREF and the
      postoperative ODI was statistically significant. CONCLUSIONS: The results of this
      study indicate that the Korean version of the ODI is a reliable and valid
      instrument for the measurement of disability in Korean patients with lower back
      problems. The authors recommend this Korean version of the ODI for use in future
      clinical studies in Korea.

PMID- 15738776
TI  - Atlanto-occipital dislocation with traumatic pseudomeningocele formation and post
      traumatic syringomyelia.
AB  - STUDY DESIGN: A case report of traumatic atlanto-occipital dislocation
      complicated by the development of anterior and posterolateral pseudomeningoceles
      and the late development of syringohydromyelia is presented. OBJECTIVE: To
      describe a unique post-traumatic and postsurgical course following atlanto
      occipital dislocation. SUMMARY OF BACKGROUND DATA: Syringomyelia is a significant
      potential long-term complication in patients recovering from traumatic atlanto
      occipital dislocation. Cord enlargement and increased T2 signal can be a marker
      of abnormal cerebrospinal fluid flow dynamics. This "presyrinx state" can be seen
      before clinical evidence of neurologic compromise. Pseudomeningocele formation
      after atlanto-occipital dislocation is rare, with only 3 reported cases. To our
      knowledge, all reported cases describe retropharyngeal pseudomeningoceles, and
      posterolateral pseudomeningocele as seen in this case has not previously been
      described. METHODS: A single case is reported with an emphasis on the imaging
      findings related to the patient's subsequent neurologic deterioration. RESULTS:
      Following a pedestrian-motor vehicle collision, the patient received initial
      evaluation and treatment at a local foreign medical facility, where his cervical
      spine was cleared. Several days following stabilizing treatment and surgery, the
      patient was transferred to a foreign-based United States military medical
      facility and ultimately to our institution, where magnetic resonance imaging
      demonstrated occipitocervical dissociation. The patient was taken to the
      operating room for surgical stabilization. Four months after his index operation,
      the patient underwent halo removal. Follow-up magnetic resonance imaging revealed
      thickening of the cervical spinal cord in conjunction with diffuse high cord T2
      signal and a small low cervical segment of syringomyelia. The patient was
      observed with follow-up magnetic resonance imaging obtained after 1 month. At
      this time, the low cervical syrinx had enlarged slightly, a small thoracic syrinx
      was observed, and cine imaging of cerebrospinal fluid flow demonstrated
      obstruction at the level of the foramen magnum. The patient was taken to the
      operating room fordecompression of the foramen magnum and posterior fossa and
      duraplasty. One month later, the patient's clinical condition began to
      deteriorate, and repeat imaging showed continued enlargement of the patient's
      syrinx and hydrocephalus. He was admitted for an urgent shunt procedure but
      unfortunately sustained cardiorespiratory arrest while on the ward awaiting
      surgery. CONCLUSIONS: Atlanto-occipital dislocation is rarely survivable, and
      delayed diagnosis can negatively affect long-term clinical outcome. This case
      illustrates how, despite early signs of improvement, post-traumatic syringomyelia
      may occur months or even years after spinal trauma and should always be
      considered in patients who experience late neurologic deterioration after atlanto
      occipital dislocation.

PMID- 15738778
TI  - Effect of segmental artery ligation on the blood supply of the thoracic spinal
      cord during anterior spinal surgery: a quantitative histomorphological fresh
      cadaver study.
AB  - STUDY DESIGN: Human cadaver quantitative morphometric analysis of the blood
      vessels in the spinal cord after ligation of segmental arteries. OBJECTIVES: To
      investigate the effect of ligation of segmental arteries on the quantity and
      density of the blood vessels in the spinal cord. SUMMARY OF BACKGROUND DATA:
      Ligation of segmental arteries is often used in the anterior approach for
      correction scoliosis. However, whether or not segmental artery ligation is liable
      to deny the spinal cord an adequate blood supply, thus leading to paraplegia,
      still remains controversial. METHODS: Eleven fresh cadavers were divided into
      control, unilateral, and bilateral groups. For the unilateral and bilateral
      groups, 5 segmental vertebral arteries (T7-T11) were ligated unilaterally and
      bilaterally, respectively. Then, the number and density of blood vessels at
      different levels in the 3 groups were measured. RESULTS: Compared to that of the
      corresponding level in the control group, the number of blood vessels at T5 to L1
      all decreased in the ligation groups. And significant differences were found at
      T8 (82.80 +/- 16.36), T10 (77.80 +/- 19.80), and T11 (99.20 +/- 14.85) levels,
      compared to those of the corresponding levels in the control group: T8 (175.80 +/
      8. 31), T9 (176.40 +/- 32. 33), T10 (171.40 +/- 9. 73), and T11 (189.20 +/- 15.
      92). Further decrease was found at each corresponding level in the bilateral
      group, and significant differences were found at T8 (65.80 +/- 15.55), T9 (24.80
      +/- 13.43), T10 (0), T11 (0), and T12 (0) levels. Similar results were obtained
      with regard to the density of blood vessels. Significant differences were found
      at T11 (1.246 +/- 0.112) and L1 (1.349 +/- 0.109) in the unilateral group, and T9
      (0.260 +/- 0.088), T10 (0), T11 (0), T12 (0), and L1 (0.147 +/- 0.117) in the
      bilateral group compared to those of the corresponding levels in the control
      group: T9 (1.810 +/- 0.202), T10 (1.833 +/- 0.175), T11 (2.308 +/- 0.335), T12
      (2.510 +/- 0.617), and L1 (2.193 +/- 0.033). CONCLUSIONS: This study suggests
      that the more levels the ligation encompasses, the higher the risk of spinal cord
      damage. Therefore, caution should be taken when several segmental arteries are to
      be ligated in the clinical setting. What is more, bilateral ligation, which is
      worse than unilateral ligation, can lead to a significant decrease in the number
      and density of blood vessels of the spinal.

PMID- 15738779
TI  - Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose,
      and pH on rates of energy metabolism of bovine nucleus pulposus cells.
AB  - STUDY DESIGN: In vitro measurements of metabolic rates of isolated bovine nucleus
      pulposus cells at varying levels of oxygen, glucose, and pH. OBJECTIVES: To
      obtain quantitative information on the interactions between oxygen and glucose
      concentrations and pH, and the rates of oxygen and glucose consumption and lactic
      acid production, for disc nucleus cells. SUMMARY OF BACKGROUND DATA: Disc cells
      depend on diffusion from blood vessels at the disc margins for supply of
      nutrients. Loss of supply is thought to lead to disc degeneration, but how loss
      of supply affects nutrient concentrations in the disc is not known; nutrient
      concentrations within discs can normally only be calculated, because
      concentration measurements are invasive. However, realistic predictions cannot be
      made until there are data from measurements of metabolic rates at conditions
      found in the disc in vivo, i.e., at low levels of oxygen, glucose, and pH.
      METHODS: A metabolism chamber was designed to allow simultaneous recording of
      oxygen and glucose concentrations and of pH. These concentrations were measured
      electrochemically with custom-built glucose and oxygen sensors; lactic acid was
      measured biochemically. Bovine nucleus pulposus cells were isolated and inserted
      into the chamber, and simultaneous rates of oxygen and glucose consumption and of
      lactic acid production were measured over a range of glucose, oxygen, and pH
      levels. RESULTS: There were strong interactions between rates of metabolism and
      oxygen consumption and pH. At atmospheric oxygen levels, oxygen consumption rate
      at pH 6.2 was 32% of that at pH 7.4. The rate fell by 60% as oxygen concentration
      was decreased from 21 to 5% at pH 7.4, but only by 20% at pH 6.2. Similar
      interactions were seen for lactic acid production and glucose consumption rates;
      we found that glycolysis rates fell at low oxygen and glucose concentrations and
      low pH. Equations were derived that satisfactorily predict the effect of nutrient
      and metabolite concentrations on rates of lactic acid production rate and oxygen
      consumption. CONCLUSIONS: Disc cell metabolism in air and at pH 7.4 differs
      markedly from that found in the disc nucleus in vivo, where low levels of oxygen,
      glucose, and pH all coexist.

PMID- 15738780
TI  - The adeno associated viral vector as a strategy for intradiscal gene transfer in
      immune competent and pre-exposed rabbits.
AB  - STUDY DESIGN: Experimental animal study. OBJECTIVES: This study evaluates the in
      vitro and in vivo transduction efficacy and transgene expression in immune
      competent and pre-exposed rabbits. SUMMARY OF BACKGROUND DATA: Degenerative disc
      disease (DDD) continues to pose a substantial clinical problem. Therapeutic
      options such as an interbody fusion are highly invasive and result in the loss of
      the intervertebral disc. In addition, interbody fusion puts the adjacent discs at
      an even higher risk for disc degeneration. A novel approach to slow DDD is to
      introduce high levels of growth factors into the degenerating disc by delivering
      the gene coding for the appropriate growth factor. The most efficient technique
      to do so to date uses viral vectors. However, viral vectors may be problematic
      because of their immunogenicity. The adeno-associated virus (AAV) viral vector is
      known to be less immunogenic than commonly used adenoviral vectors. METHODS:
      Human nucleus pulposus cells were transduced in vitro. Twenty-four Rabbits were
      injected with AAV viral vectors carrying different marker genes. Transgene
      expression and the humoral/cellular immune response to the vector was evaluated.
      RESULTS: We could show that the AAV viral vector transduces human as well as
      rabbit nucleus pulposus cells in vitro and in vivo. There is a significant
      humoral immune response against the AAV vector that decreases transgene
      expression over 10-fold in preimmunized animals. CONCLUSIONS: AAV is a valuable
      new vector to achieve transgene expression in the intervertebral disc. In
      preimmunized animals, its use needs to be further evaluated because of the
      significant reduction in transgene expression.

PMID- 15738781
TI  - Segmental variation in the in vitro cell metabolism of nucleus pulposus cells
      isolated from a series of bovine caudal intervertebral discs.
AB  - STUDY DESIGN: This study focuses on the association between cell metabolism and
      molecular matrix composition of nucleus pulposus (NP) tissue with spine level in
      sequential bovine caudal intervertebral discs. OBJECTIVE: To explore the
      hypothesis that the molecular composition of NP tissue and corresponding cell
      metabolism varies with caudal spine. A secondary hypothesis is tested that
      potential cellular differences are maintained after monolayer culture. SUMMARY OF
      BACKGROUND DATA: In articular cartilage, cell metabolism and molecular matrix
      composition are influenced by loading history. This may also be a feature of
      intervertebral discs in series. METHODS: NP cells (nonpooled or level pooled)
      were isolated from four sequential bovine caudal intervertebral discs (levels 3
      4, 4-5, 5-6, and 6-7) and cultured in alginate beads immediately or following
      monolayer culture. Levels of 3H-TdR (proliferation) and 35SO4 (GAG synthesis)
      incorporation were determined from 14 animals. In a separate set of 6 animals,
      total content of water, DNA, collagen (and type), GAG (and type) were also
      determined. RESULTS: The rate of 3H-TdR and 35SO4 incorporation in freshly
      isolated NP cells increased nonlinearly from level 3-4 to 6-7 (P < 0.05).
      Monolayer cultured cells retained level-specific differences for 35SO4 and 3H-TdR
      incorporation similar to that of freshly isolated cells. GAG content and
      chondroitin sulfate proportion decreased distally (P < 0.05); however, total
      collagen and Type I proportion increased distally (P < 0.05). No significant
      differences in water or DNA content could be determined. CONCLUSIONS: The results
      support the hypothesis that level-specific differences in NP cell metabolism and
      molecular composition are dependent on spine level potentially reflecting subtle
      mechanical differences between levels. Retention of level-specific differences in
      monolayer may suggest a certain level of cell "programming." This may be
      important for cellular strategies to repairspecific sites of degeneration.

PMID- 15738782
TI  - Recombinant human bone morphogenic protein-2-enhanced anterior spine fusion
      without bone encroachment into the spinal canal: a histomorphometric study in a
      thoracoscopically instrumented porcine model.
AB  - STUDY DESIGN: A thoracoscopically assisted 5-level anterior spinal fusion and
      instrumentation model analyzing new bone formation when using recombinant human
      bone morphogenic protein-2 (rhBMP-2) with a collagen hydroxyapatite-tricalcium
      phosphate (HA/TCP) composite sponge carrier. OBJECTIVE: To determine whether new
      bone formation extends beyond the posterior confines of the vertebral body
      encroaching into the spinal canal when rhBMP-2 is used to enhance anterior
      fusion. SUMMARY OF BACKGROUND DATA: A possible concern regarding the use of rhBMP
      2 to enhance spinal fusion is the risk of unwanted bone formation leading to
      inadvertent fusion of adjacent levels or compression of neural elements. The
      safety of rhBMP-2 in one spinal application does not ensure similar results in
      other applications. Therefore, the expanded use of rhBMP-2 should occur only
      after carefully monitored preclinical and clinical studies for each new
      application. METHODS: Eighteen pigs underwent thoracoscopically-assisted
      instrumentation and fusion of 5 contiguous levels (T5-T10) and randomly assigned
      to 4 treatment groups: group 1 (n = 6): rh-BMP-2 on a HA/TCP-collagen sponge
      (Medtronic Sofamor Danek, Memphis, TN); group 2 (n = 4): iliac crest autograft;
      group 3 (n = 4): empty; group 4 (n = 4): HA/TCP-collagen sponge (Medtronic
      Sofamor Danek) only. In groups 1 and 4, the HA/TCP collagen sponge was morselized
      into small granules and pushed through a bone delivery funnel for implantation
      into the disc. At 4 months after surgery, spines were sectioned longitudinally
      through the midsagittal plane and underwent undecalcified processing. Bone
      formation extending beyond the margins of the original discectomy and the
      confines of vertebral body were evaluated histomorphometrically at each operative
      level. RESULTS: Recombinant human bone morphogenic protein-2 on a HA/TCP-collagen
      sponge induced significant new bone formation extending anterior to the confines
      of the vertebral body compared with the other treatment groups (P < 0.05). In
      addition, rhBMP-2 on a HA/TCP-collagen sponge induced significant new bone
      formation extending posterior to the original margins of the discectomy (P <
      0.05). However, there was no new bone formation beyond the confines of the
      posterior vertebral body. The total bone volume in the rhBMP-2-HA/TCP-collagen
      sponge group was significantly greater compared with all other groups in both the
      discectomy fusion area and beyond the discectomy area (P < 0.05). CONCLUSIONS:
      Recombinant human bone morphogenic protein-2 on a HA/TCP-collagen sponge enhanced
      anterior spinal fusion and induced significant new bone formation extending
      beyond the margins of the original discectomy and anterior vertebral body, most
      likely secondary to migration of some morselized carrier fragments from the disc
      space. However, the new bone formation did not extend beyond the posterior
      confines of the vertebral body to encroach into the spinal canal because of the
      intact posterior anulus and/or posterior longitudinal ligament.

PMID- 15738783
TI  - Occurrence and regional distribution of apoptosis in scoliotic discs.
AB  - STUDY DESIGN: Seventy surgically obtained intervertebral discs from 9 patients
      with idiopathic and 7 patients with neuromuscular scoliosis were analyzed for the
      regional distribution of apoptosis. OBJECTIVES: To investigate the role of
      apoptotic mechanisms in scoliotic discs. SUMMARY OF BACKGROUND DATA: The reasons
      for the development of scoliosis are complex and yet not completely understood.
      In herniated lumbar disc tissue, increased apoptosis and a high expression of Fas
      and Fas ligand and caspase-3 activity have already been reported, suggesting a
      pivotal role of apoptotic mechanisms in intervertebral disc degeneration. In
      scoliotic discs, cell death was correlated with disc deformity and changes in
      nutrient supply and metabolic levels. The role of apoptosis in scoliotic discs,
      however, is still unclear. METHODS: Apoptosis was determined by terminal
      deoxyribonucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL)
      assay and poly(ADP-ribose) polymerase (PARP) p85 immunohistochemistry. Expression
      of Fas and Fas-ligand was analyzed by immunohistochemistry and reverse
      transcription polymerase chain reaction analysis. RESULTS: In all samples
      analyzed, apoptotic cells could be detected in the nucleus, anulus, and endplate.
      The number of apoptotic cells was significantly higher in the nucleus compared to
      the other areas and in the apex versus the nonapex discs. There was no difference
      between the discs of idiopathic and neuromuscular scoliosis and between the 2 age
      groups studied (10-17 years and 17-48 years, respectively). A strong expression
      of Fas and Fas-ligand could be detected in all samples. CONCLUSION: Increased
      numbers of apoptotic cells in the nucleus of scoliotic discs and the apex disc
      suppose a pivotal role of programmed cell death for the progression of this
      common disorder. The simultaneous increase of Fas and Fas-ligand expression in
      areas with increased cell death point to an activation of the apoptotic process
      via the Fas/Fas-L system.

PMID- 15738784
TI  - A stronger bicortical sacral pedicle screw fixation through the s1 endplate: an
      in vitro cyclic loading and pull-out force evaluation.
AB  - STUDY DESIGN: The insertion torque and pull-out force after cyclic loading of the
      bicortical sacral pedicle screw through the S1 endplate were tested using human
      cadaveric specimens. OBJECTIVES: The purpose of this study was to (1) evaluate
      the effect of cyclic loading on the pull-out force of two different techniques of
      bicortical sacral pedicle screw fixation and (2) to correlate the pull-out force
      after cyclic loading with the screw insertion torque. SUMMARY OF BACKGROUND DATA:
      Biomechanical studies using conventional sacral pedicle screw fixation techniques
      have demonstrated reduction in stiffness and strength after cyclic loading.
      Technical difficulties with anterior sacral cortex penetration and frequent screw
      loosening have been reported in clinical studies. In the authors' center, a new
      method of sacral pedicle screw fixation bicortically through the S1 endplate has
      been used successfully in the clinical setting. However, the mechanical stability
      of this new technique after undergoing cyclic loading has not been documented in
      the literature. METHODS: Seven-millimeter compact Cotrel-Dubousset sacral screws
      were randomly assigned by side (left vs. right) and inserted bicortically either
      anteromedially through the anterior sacral cortex or superiorly through the S1
      endplate of 17 fresh frozen human sacrum. The tk;4maximum insertion torque for
      each screw was measured. Cyclic loading from 40 N to 400 N was applied to each
      screw at a frequency of 2 Hz for 20,000 cycles. Pull-out tests were conducted
      after completion of the cyclic tests. RESULTS: The mean maximum insertion torque
      and mean pull-out force following cyclic loading were significantly higher for
      bicortical fixation through the S1 endplate (mean 3.17 N.m and 1457 N) than
      bicortical fixation through the anterior sacral cortex (mean 1.98 N.m and 1122
      N). Both S1 endplate and anterior cortical fixation techniques demonstrated
      significant correlations between insertion torque and pull-out force following
      cyclic loading. CONCLUSIONS: In sacral pedicle screw fixation, screw trajectory
      through the S1 endplate was significantly stronger than screws penetrating the
      anterior sacral cortex. Insertion torque was a good intraoperative indicator of
      screw pull-out force after cyclic loading.

PMID- 15738785
TI  - Occipitocervical fixation: long-term results.
AB  - STUDY DESIGN: The study is a retrospective review of 58 patients who underwent
      occipitocervical fusion between 1997 and 2001. OBJECTIVES: Our objective is to
      study the clinical results after occipitocervical fixation with long-term follow
      up and assess factors contributing to clinical success. METHODS: Data from
      patient charts, operative notes, physician office notes, and imaging studies were
      incorporated in the study. Myelopathy was assessed using a Nurick scale for
      preoperative and postoperative evaluation. Fusion was assessed using cervical
      plane films with flexion and extension views. RESULTS: Mean follow-up was 36
      months, with all patients having a greater than 1-year follow-up. The most common
      pathology was congenital cranial settling (41%) followed by trauma (22%) and
      rheumatoid arthritis (17%). Myelopathy was the most common presentation (62%)
      followed by pain (28%). A successful fusion occurred in 48 out of 51 patients
      (94%). Symptoms improved in 86% of patients, whereas 35% improved 1 Nurick grade.
      Complications occurred in 30% of patients. The cervical wound infection rate was
      5%. The rate of adjacent level degeneration was 7%. The mortality rate was 1.7%.
      CONCLUSIONS: Occipitocervical instrumentation allows for very high fusion rates
      without the need for halo vest immobilization. All patients with successful
      fixation have pain resolution. Myelopathy improves in most patients, whereas one
      third of patients demonstrate dramatic improvement.

PMID- 15738786
TI  - Cervical muscle response to head rotation in whiplash-type left lateral impacts.
AB  - STUDY DESIGN: Twenty healthy volunteers were subjected to left lateral impacts,
      randomly looking either left or right. OBJECTIVES: The purpose of this study is
      to determine the response of the cervical muscles to lateral impact whiplash-type
      perturbations when the head is rotated at the time of impact. SUMMARY OF
      BACKGROUND DATA: A previous study of left lateral impacts with head in neutral
      posture suggests that the burden of impact is borne primarily by the splenius
      capitis muscles. In order to improve automobile designs to prevent whiplash
      injury, we need to understand the response of the cervical muscles to whiplash
      type perturbations in less-than-ideal conditions, such as when the head is
      rotated to the right and at the time of lateral impact. METHODS: Bilateral
      electromyograms of the sternocleidomastoids, trapezii, and splenii capitis were
      recorded. Triaxial accelerometers recorded the acceleration of the sled, torso,
      and head of the participant. RESULTS: For participants experiencing a left
      lateral impact, whether having the head rotated to the left or right at the time
      of impact, the muscle responses generally increased with increasing levels of
      acceleration (P < 0.05). The time of onset and peak electromyograph reading for
      most muscles progressively decreased with increasing acceleration. Overall,
      however, muscle responses were of low magnitude with the head rotated to the left
      or right. The sternocleidomastoid muscle responsible for head rotation (i.e.,
      right sternocleidomastoid muscle when looking left) had a greater electromyograph
      response than its counterpart (P < 0.05). The contralateral splenius capitis and
      trapezius had the highest electromyograph responses. The remaining muscles showed
      similar levels of electromyograph responses, but even at the highest acceleration
      of 12.8 m/s, all generated less than 45% of their maximal voluntary contraction
      electromyograph reading. CONCLUSIONS: Compared to a lateral impact with the
      volunteer's head in the neutral position, a lateral impact with head rotation to
      either right or left may reduce the muscle response. Further studies are needed
      to determine whether or not head rotation at the time of lateral impact reduces
      overall injury risk.

PMID- 15738787
TI  - The updated cochrane review of bed rest for low back pain and sciatica.
AB  - STUDY DESIGN: A systematic review within the Cochrane Collaboration Back Review
      Group. OBJECTIVES: To report the main results from the updated version of the
      Cochrane Review on bed rest for low back pain. SUMMARY OF BACKGROUND DATA: There
      has been a growing amount of evidence showing that bed rest is not beneficial for
      people with low back pain. However, existing systematic reviews are unclear
      regarding the effects of bed rest for different types of low back pain. METHODS:
      All randomized studies available in systematic searches up to March 2003 were
      included. Two reviewers independently selected trials for inclusion assessed the
      validity of included trials and extracted data. Investigators were contacted to
      obtain missing information. RESULTS: Two new trials comparing advice to rest in
      bed with advice to stay active were included. There is high quality evidence that
      people with acute low back pain who are advised to rest in bed have a little more
      pain (standardized mean difference 0.22, 95% confidence interval: 0.02-0.41) and
      a little less functional recovery (standardized mean difference 0.29, 95%
      confidence interval: 0.05-0.45) than those advised to stay active. For patients
      with sciatica, there is moderate quality evidence of little or no difference in
      pain (standardized mean difference -0.03, 95% confidence interval: -0.24-0.18) or
      functional status (standardized mean difference 0.19, 95% confidence interval: 
      0.02-0.41) between bed rest and staying active. CONCLUSION: For people with acute
      low back pain, advice to rest in bed is less effective than advice to stay
      active. For patients with sciatica, there is little or no difference between
      advice to rest in bed and advice to stay active.

PMID- 15738788
TI  - Psychologic management of brace therapy for patients with idiopathic scoliosis.
AB  - STUDY DESIGN: A trial of brace therapy modified by a measured personality pattern
      of patients with idiopathic scoliosis was performed. OBJECTIVE: To evaluate the
      effectiveness of performing personality tests for patients with idiopathic
      scoliosis who undergo brace therapy. SUMMARY OF BACKGROUND DATA: Brace therapy
      has often been used for the treatment of scoliosis. However, emotional distress
      can result from this therapy. Few attempts have been made to reduce such stress.
      METHODS: A test using the Maudsley Personality Inventory was performed on 145
      adolescent females with idiopathic scoliosis, treated with brace therapy alone,
      before the start of brace therapy and 1 month after the start of brace therapy.
      On the basis of test results, the patients were rated as normal type and four
      abnormal types. Brace therapy was continued considering the personality pattern
      of patients. For all patients, changes in psychologic test results, compliance
      with braces wearing instructions, and correction of scoliosis were analyzed.
      RESULT: Of the 134 patients rated as normal before the start of therapy, 108
      patients were rated as abnormal pattern when tested 1 month after the start of
      therapy. After performing autogenic training for patients with E-N+ and E-N-
      personalities, and giving advice to school teachers to decrease the emotional
      stress for patients with E+N+ personality, 47 patients were finally rated as
      abnormal pattern. In total, 12 (8%) of the 145 patients dropped out. In dropouts,
      the average pretreatment deformity of 29 degrees (range: 21 degrees -37 degrees )
      had increased to an average of 37 degrees (range, 31 degrees -48 degrees ).
      CONCLUSION: Psychologic tests may be useful and provide a means of modifying
      brace therapy tailored to the psychologic conditions of individual patients.

PMID- 15738789
TI  - Predicting health-related quality of life in patients with low back pain.
AB  - STUDY DESIGN: Cross-sectional surveys of health-related quality of life (HRQOL)
      in patients with low back pain at ambulatory clinics plus 8 weeks of follow-up.
      OBJECTIVE: The objective of this study is to predict the HRQOL in patients with
      low back pain. SUMMARY OF BACKGROUND DATA: There is disagreement on the relative
      contribution of pain, physical impairment, functional status, and psychological
      factors on the disability and HRQOL in patients with low back pain. METHODS: Data
      were collected from 232 patients with low back pain who were consecutively
      recruited from several clinics of physical medicine and rehabilitation. Every
      patient received physical examination and completed a set of questionnaire,
      including the Taiwan version of the Brief Questionnaire of the World Health
      Organization on quality of life (WHOQOL-BREF), Modified Roland and Morris
      Disability Questionnaire, and visual analogue scale for pain intensity and for
      HRQOL. These patients were observed with a mail questionnaire 8 weeks later. The
      results of WHOQOL-BREF were also compared to those obtained from another 213
      healthy volunteers who were accompanied persons with patients, volunteer workers
      in hospitals, and hospital employees. RESULTS: Results showed that there were
      significant correlations of HRQOL with pain intensity, disability scale, and
      disability days. Among the results of physical examination, lumbosacral
      radiculopathy was the only factor with moderate correlation with HRQOL. The
      significant predictors for HRQOL included physical domain, psychological domain,
      pain intensity, and family income. Among all the 232 study patients, 100 of them
      responded to the follow-up questionnaire. Changes in environmental domain,
      disability days, educational level, receiving herb drugs, and physiotherapy were
      the significant predictors for the changes of HRQOL. CONCLUSIONS: The HRQOL of
      patients with low back pain depended on functional status and psychological
      factors more than simple physical impairment. Future intervention may need to put
      more emphasis on improving functional status and psychological stress for these
      patients.

PMID- 15738790
TI  - Three-dimensional rotational X-ray imaging for spine surgery: a quantitative
      validation study comparing reconstructed images with corresponding anatomical
      sections.
AB  - STUDY DESIGN: A validation study was done in which reconstructed three
      dimensional rotational x-ray images were quantitatively compared with
      corresponding anatomic sections. OBJECTIVES: To assess the accuracy of
      reconstructed images acquired on a three-dimensional rotational x-ray imaging
      device. SUMMARY OF BACKGROUND DATA: Minimally invasive procedures have proven
      quite successful as alternatives for a multitude of open treatments. An
      unfavorable property of this type of procedure is a lack of direct vision of the
      operating area. Three-dimensional rotational x-ray imaging may be able to merge
      the advantages of computed tomography and fluoroscopy: real-time two-dimensional
      projections for fast visual feedback and three-dimensional reconstructions for
      detailed volumetric imaging of complex anatomy. METHODS: Twenty traumatic
      thoracolumbar burst fractures were created and underwent pedicle screw
      instrumentation and balloon vertebroplasty. Subsequently, a three-dimensional
      dataset was obtained, and the midsagittal image was reconstructed. The specimens
      were sliced, and photographs were obtained. Multiple parameters on the
      reconstructed images and photographs were measured two times by two observers
      using a graphical method. The differences and standard deviations were calculated
      for the corresponding parameters and for the intraobserver data. RESULTS: The
      mean difference between the corresponding values ranged between -1.1 and 2.1 mm
      for all parameters. The standard deviation for the differences per parameter
      ranged between 1.2 and 3.2 mm. The intraobserver differences ranged from -0.8 to
      1.4 mm, and the standard deviation varied between 0.4 and 2.4 mm. CONCLUSIONS:
      The reconstructed midsagittal images were accurate in all measured parameters.
      The three-dimensional rotational x-ray technique may prove to be valuable for
      less invasive spine surgery.

PMID- 15738791
TI  - Expression of estrogen receptor of the facet joints in degenerative
      spondylolisthesis.
AB  - STUDY DESIGN: Immunohistochemical study was done by harvesting articular
      cartilage of the facet joints during the decompressive surgery for spinal
      stenosis. OBJECTIVES: To observe the expression of estrogen receptor on the
      articular cartilage of the facet joints in degenerative spondylolisthesis (DS)
      SUMMARY OF BACKGROUND DATA: Few attempts have been made to evaluate the effect of
      sex-hormone, although DS is more common in females than in males. METHODS: After
      harvesting the articular cartilage of the facet joints in 17 DS and in 15 spinal
      stenosis (SS) patients, the expression of estrogen receptor and the severity of
      facet arthritis were observed by H-E and immunohistochemical staining,
      respectively. Measurements of both staining were made by using a semiquantitative
      analysis. RESULTS: The significantly increased expression of estrogen receptor
      correlated with the severity of facet arthritis (r = 0.78, P < 0.05). There was a
      significantly increased expression of estrogen receptor of the facet joint in DS
      compared with SS (P < 0.01). The histologic-histochemical grading of cartilage
      lesion in DS was 12.4 (SEM, 0.6), which was significantly higher than in SS (P <
      0.05). CONCLUSIONS: These findings suggest that the higher expression of estrogen
      receptor might aggravate degenerative change of the facet articular cartilage and
      might also be considered one of the causative factors for DS in postmenopausal
      women.

PMID- 15738792
TI  - Acute low back pain: diagnostic and therapeutic practices reported by Brazilian
      rheumatologists.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVES: To assess resource utilization
      in the diagnosis, management, and hospitalization of patients with low back pain
      (LBP) as prescribed by Brazilian rheumatologists. SUMMARY OF BACKGROUND DATA: LBP
      is an important cause of disability, suffering, and social costs. Two to five
      percent of patients miss workdays because of LBP; it is the second highest cause
      of physician visits and absenteeism. METHODS: Rheumatologists taking part in a
      national rheumatology medical congress answered a questionnaire to assess
      management of patients with LBP. It consisted of two hypothetical scenarios
      describing patients with acute LBP (scenario 1) and sciatica (scenario 2). There
      were 29 questions mainly related to education, protective measures, rest, and
      medication. RESULTS: A total of 207 questionnaires were returned. In scenario 1,
      70% of the participants ordered some diagnostic test at first visit; lumbar
      radiograph was the most ordered (92%), while more than 80% prescribed rest and
      100% at least one drug. Nonsteroidal anti-inflammatory drugs were prescribed by
      69% of the participants. In scenario 2, 93% of the physicians ordered diagnostic
      tests at first visit, with computed tomography being the most ordered test (69%).
      Rest was prescribed by 90% (average 18 days) of the participants and physical
      therapy was counseled by 84%. CONCLUSIONS: Considering the hypothetical
      scenarios, participants overused diagnostic and therapeutic procedures. A
      dissemination of guidelines for optimizing resource use in LBP diagnosis and
      management is needed.

PMID- 15738793
TI  - Early disability risk factors for low back pain assessed at outpatient
      occupational health clinics.
AB  - STUDY DESIGN: Inception cohort (<or=14 days after pain onset) with 1-month follow
      up. OBJECTIVE: To determine whether disability risk factors provided by patients
      and clinicians at a first medical visit for acute occupational low back pain
      predict outcomes. SUMMARY OF BACKGROUND DATA: Improving health and work outcomes
      for patients with occupational low back pain may require early identification of
      risk factors for persistent pain and disability. Previous studies of back pain
      prognosis have not assessed patients at the time of initial provider contact, and
      many have not differentiated between occupational and nonoccupational injuries.
      METHOD: Patients (183 female, 385 male) presenting to occupational health clinics
      with recent onset occupational low back pain (<or=14 days duration) completed a
      16-item survey of potential disability risks including demographic, injury,
      workplace, psychosocial, and symptom factors. After the initial visit, clinicians
      completed an additional 10-item questionnaire of symptoms and initial prognosis.
      Outcome variables of functional limitation and work status were assessed 1 month
      after pain onset. RESULTS: In multivariate analyses, functional improvement and
      return to work were more strongly predicted by employer factors (job tenure,
      physical work demands, availability of modified duty, earlier reporting to
      employer) and self-ratings of pain and mood than by health history or physical
      examination. A logistic regression model had a sensitivity of 74.3% to predict
      those remaining out of work and a specificity of 70.1%. CONCLUSIONS: Early
      screening for disability risk factors may be helpful to identify those patients
      at greatest risk for delayed recovery from occupational low back pain.
      Intervention strategies for high-risk patients might be improved by focusing on
      job factors, pain coping strategies, and expectations for recovery.

PMID- 15738794
TI  - Early patterns of care for occupational back pain.
AB  - STUDY DESIGN: Cross-sectional analysis. OBJECTIVES: To describe the early health
      care utilization for occupational back pain. To identify factors associated with
      health care seeking and provider choice among persons with occupational back
      pain. SUMMARY OF BACKGROUND DATA: Back pain is the most prevalent work-related
      injury, yet little is known about patterns of care for occupational back pain.
      MATERIALS AND METHODS: The sample includes 1104 workers with incident episodes of
      low back pain. Outcomes measures include whether or not workers received care and
      the types of providers seen. Predictors of outcomes include demographics, injury
      severity, history of back pain, occupation, and employer. RESULTS: Eight percent
      of workers did not receive care in the first 4 to 16 weeks after filing a
      workers' compensation claim. Injury severity, gender, occupation, and employer
      were significant predictors of the decision to seek care. Almost 90% of workers
      who received care were treated by medical physicians, often in combination with
      physical therapists or chiropractors. Age, occupation, injury severity, and
      whether the employer or worker chose the initial health care provider were
      associated with the choice of provider. Employers selected providers for 78% of
      injured workers who received care. Medical physicians were the providers most
      often chosen by both employers and workers, but workers were more likely than
      employers to select chiropractors. CONCLUSIONS: A small but significant number of
      injured workers do not seek care for their back pain. Medical physicians treat
      all but a small fraction of the workers who receive care. The decision to seek
      care and the choice of providers is associated with injury severity, occupation,
      and employer actions.

PMID- 15738795
TI  - Non-fusion surgery for degenerative spondylolisthesis using artificial ligament
      stabilization: surgical indication and clinical results.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: To report midterm clinical and
      radiographic results of Graf artificial ligament stabilization in the treatment
      of degenerative spondylolisthesis and to evaluate the role of this procedure and
      its surgical indications for surgical success. SUMMARY OF BACKGROUND DATA:
      Nonfusion surgeries including artificial disc replacement and ligamentoplasty are
      increasingly gaining interest to avoid adverse effects of spinal fusion. METHODS:
      Sixty-four consecutive patients with degenerative spondylolisthesis underwent
      artificial ligament stabilization. Surgical indication was symptomatic
      degenerative spondylolisthesis with <25% of vertebral slip, coronal facet
      tropism, and minimal disc space narrowing. Radiographic and clinical assessments
      were performed before surgery, immediately after surgery, and at the final follow
      up. Mean follow-up period was 67 months (36-112 months). RESULTS: Visual analog
      scales of low back pain and sciatic symptoms were significantly improved.
      Radiographic assessments demonstrated that segmental lordosis was maintained in
      12.2 degrees , and flexion-extension motion was averaged 4.7 degrees at the final
      follow-up. Facet arthrodesis spontaneously occurred in 12 cases (18.8%) at an
      average of 59.5 months after surgery. Although vertebral slip was not improved,
      postoperative disc space narrowing was minimal. Additional surgeries were
      required in 4 cases for adjacent segment pathologies (6.3%). One patient (1.6%)
      underwent consequent spinal arthrodesis at the ligamentoplasty level.
      CONCLUSIONS: Artificial ligament stabilization did not improve the vertebral slip
      but maintained lordosis and preserved segmental motion in 80% of patients. This
      procedure is an effective alternative to spinal arthrodesis in the treatment of
      symptomatic degenerative spondylolisthesis (Grade I) with minimal disc space
      narrowing and coronal facet tropism.

PMID- 15738796
TI  - Re: Murakami H, Kawahara N, Gabata T, et al. Vertebral body osteonecrosis without
      vertebral collapse. Spine 2003;28:323-8.

PMID- 15738798
TI  - Forearm fractures in children. 1967.

PMID- 15738799
TI  - Pediatric skeletal trauma: a review and historical perspective.
AB  - Pediatric fractures are commonly classified into five types: plastic deformation,
      buckle fracture, greenstick fracture, complete fracture, and physeal injuries.
      The most important anatomic characteristic in the pediatric skeleton is the
      presence of growth plates and the thick periosteum. It is important to emphasize
      that just as adult intra-articular fractures require anatomic reduction, so do
      pediatric articular injuries. The periosteum in children contributes immensely to
      rapid fracture healing and helps in the reduction and in the maintenance of
      reduction. In this study, I review some basic principles for the treatment of
      fractures in children, the main complications of pediatric fractures, and the
      outcomes assessment in children. The main complications of fractures in children
      are malalignment, physeal arrest, and refracture cause by fast fracture healing.
      Nearly all fractures in children can be treated in a cast without worry about
      stiff joints or need for physical therapy to mobilize injured joints.

PMID- 15738800
TI  - Bone development: interaction of molecular components and biophysical forces.
AB  - A deeper understanding of skeletal development comes from knowledge of the
      molecular components, cell and tissue structure, and biophysical and vascular
      mechanisms underlying physiologic function. Endochondral and intramembranous bone
      formation mechanisms are active during long bone synthesis. Most endochondral
      growth in length occurs at the physes by the coordinated actions of cell
      proliferation, matrix synthesis, and chondrocyte hypertrophy. Several intrinsic
      molecules act to modulate physeal structure and function whereas extrinsic
      molecules, such as hormones, provide systemic regulation of growth. Biophysical
      forces develop intrinsically within the growing bone, serving to enlarge it in
      three dimensions, while extrinsic forces resist and channel expansion into normal
      recognizable and functional forms. Newer imaging modalities, such as magnetic
      resonance imaging, are highly effective in assessing epiphyseal vascularity and
      differentiating fibrous, cartilaginous, mineralized and osseous tissues in
      prenatal and postnatal developing bone. This study illustrates the interplay
      between the molecular and biophysical aspects of normal bone growth, shows ways
      in which altered development leads to abnormal structures, and provides examples
      where biologic and biophysical interventions can affect bone development in
      favorable ways.

PMID- 15738801
TI  - Pediatric spinal trauma: injuries in very young children.
AB  - Injuries to the spine in very young children are comparatively rare. The
      prevalence of upper cervical injuries and spinal cord injuries is greater. Spinal
      cord injury is more common in young children and fracture is less common than in
      older children and adolescents. This is because of the anatomic and biomechanical
      differences in the growing spine including a more horizontal facet orientation,
      greater elasticity of the soft tissues, less muscular development, and relatively
      greater head size compared to the trunk. These features are more pronounced in
      the very young child. The clinical and radiographic evaluation of small children
      can be difficult. Unossified bone and physeal cartilage can be confused with
      fractures. The evaluation, safe transportation, and spinal clearance of the
      unconscious multiply injured child suspected of having spinal injury present
      special challenges.

PMID- 15738802
TI  - Pediatric shoulder trauma.
AB  - Pediatric shoulder trauma is relatively uncommon. Injuries requiring surgical
      intervention are even rarer. However, it is important for the practicing
      orthopaedic surgeon to differentiate nonoperative injuries from the urgent and
      potentially operative injuries. Missing such an injury in the pediatric
      population could be potentially life threatening or lead to long-term disability.
      Posterior sternoclavicular dislocations should be differentiated from medial
      clavicular physeal injuries and promptly reduced. Open fractures or neurovascular
      threatening fractures should be attended to immediately. Severely displaced
      proximal physeal humerus fractures in the older child often have a better long
      term outcome after anatomic reduction. Finally, although glenohumeral
      dislocations, once reduced, are not life threatening or limb threatening, they do
      have a very high incidence of recurrence in adolescent patients. This should be
      kept in mind when formulating the treatment plan. If these overall treatment
      recommendations and plans are adhered to, the majority of pediatric shoulder
      trauma will result in a good outcome.

PMID- 15738803
TI  - Pediatric fractures of the humerus.
AB  - Humeral shaft fractures constitute only 3% of fractures in children younger than
      age 16 years. They are most common in children younger than 3 and older than 12
      years old. They can be classified according to the fracture pattern, location,
      and tissues damaged. Fractures resulting from minor trauma may be caused by an
      occult unicameral bone cyst. Each age group requires different diagnosis,
      treatment, and prognosis. Fractures at birth are seen mostly with macrosomic and
      breech presentation. In children younger than 3 years, humeral fractures often
      are linked to child abuse. In those older than 10 years, fractures are related to
      direct or indirect trauma. Sports activities have been reported also to cause
      injuries in skeletally immature patients. Most humeral fractures are controlled
      nonoperatively; however, potential operative indications include open fractures,
      multiple trauma, bilateral injuries, compartment syndromes, pathological
      fracture, significant nerve injuries, and inadequate closed reduction.

PMID- 15738804
TI  - Supracondylar fractures of the humerus in children.
AB  - Supracondylar fractures of the humerus need a precise treatment in order to
      obtain a satisfactory result because of the low bone remodeling associated with
      these injuries. It is important to use a systematic procedure for closed
      reduction and percutaneous fixation. A retrospective review of fractures treated
      using two K-wires from the lateral side was done in 77 patients with a mean age
      of 6.7 years (range, 1-13 years). Displacement of the fracture was classified as
      Gartland Type II in 39 patients (50.6%) and Gartland Type III in 38 patients
      (49.4%). The results according to Flynn criteria were excellent in 70 patients
      (90.9%), fair in three patients (3.9%) and poor in four patients (5.2%), with
      overall satisfactory results in 96.1% of the cases. In four patients there was
      secondary displacement of the fragments in internal rotation and three of these
      patients were operated on again, increasing fixation with a third K-wire either
      from the lateral or medial side. There were two nerve lesions (2.6%), and four
      patients (5.2%) had a pulseless pink hand that recovered when the fracture was
      reduced. In three patients (3.9%) infection developed. To obtain satisfactory
      results using this procedure, enough stability should be achieved, avoiding
      iatrogenic damage of the ulnar nerve.

PMID- 15738805
TI  - Pediatric fractures of the forearm.
AB  - Forearm fractures are common injuries in childhood. There are a number of
      important principles that should be followed to achieve the ideal goal of
      fracture healing without deformity or dysfunction. I will review the general
      principles, classifications, diagnosis, treatment, and complications of pediatric
      forearm fractures, including some specific injuries such as Monteggia fractures,
      Galeazzi injuries, and open fractures. The basic principle is to accurately align
      the fracture fragments and to maintain this position until the fracture is
      united. Forearm fractures in children can be treated differently from adult
      fractures because of continuing growth in both bones (radius and ulna) after the
      fracture has healed. As long as the physes are open, remodeling can occur.
      However, generally it is thought that rotational deformity does not remodel.
      Undisplaced fractures may be treated in a cast until the fracture site is no
      longer painful. Most displaced fractures of the forearm are best maintained in a
      long arm cast. However, redisplacement occurs in 7 to 13% of cases, usually
      within 2 weeks of injury. Unstable metaphyseal fractures should be percutaneously
      pinned. Unstable diaphyseal fractures can be stabilized by intramedullary
      fixation of the radius and ulna. If none of these techniques is helpful, plate
      and screw fixation is the best choice.

PMID- 15738806
TI  - Carpal fractures in children.
AB  - Carpal injuries in children are relatively rare. Diagnosis is likely to be
      missed, or the severity of the injury might not fully be appreciated at the time
      of presentation. Fortunately, in the majority of cases the fracture heals
      uneventfully with a low incidence of complications. As in adults, the scaphoid is
      most susceptible to injury and the capitate, which often presents in association
      with other carpal bone injuries, the next most susceptible. Other carpal bone
      fractures are very unusual and the literature largely is confined to case reports
      or very small series. This review article lists the common carpal injuries in
      children and suggests a treatment plan in each case, emphasizing the importance
      of having a high index of suspicion when faced with a child with a wrist injury
      and seemingly normal radiographs.

PMID- 15738807
TI  - Pediatric hand trauma.
AB  - Hand injuries in infants are an exciting challenge for those who treat pediatric
      trauma patients. We will review different hand injuries and provide basic rules
      for their treatment and followup. We will compare our experience with published
      results. When compared with adults, two main differences arise in treatment of
      pediatric hand injuries: children have an exceptional regenerative ability that
      allows procedures to be used that would not be useful in older patients (eg,
      replantation after avulsion injuries) and children have a high degree of
      cooperation with physicians. The main goal of treatment should be to have
      children return quickly to their daily leisure and academic activities.

PMID- 15738808
TI  - Pediatric fractures and dislocations of the hip and pelvis.
AB  - Recognition of an unstable pelvic fracture or a significant hip injury in
      children is important. Clinical assessment plays a valuable role as does the
      judicious use of imaging modalities in determining the most effective form of
      treatment, but the routine use of the standard AP pelvic radiograph is
      questioned. The concept of age and skeletal maturity has been re-evaluated,
      allowing the appropriate identification of cases that would benefit from an
      aggressive operative approach. A dual-tier approach to the treatment of pediatric
      pelvic trauma is suggested with an appreciation that there is no substantial
      evidence base for the surgical treatment of most injuries. Displaced femoral neck
      fractures and injuries to the hip joint that damage the articular or physeal
      cartilages require careful assessment and prompt and careful reduction and
      stabilization.

PMID- 15738809
TI  - Intra-articular traumatic disorders of the knee in children and adolescents.
AB  - Intra-articular knee injuries in children traditionally have been considered
      rarer than injuries in adults. Few studies establish the prevalence of knee
      injuries before skeletal maturity, but arthroscopic studies suggest an increased
      frequency of anterior cruciate ligament ruptures, meniscal tears, and
      osteochondral fractures. We report our experience with 15 anterior cruciate
      ligament injuries and 38 meniscus injuries treated between 1996 and 2001. The
      treatment of anterior cruciate ligament injuries is determined by Tanner's
      maturity criteria. In the three cases of Stage II injuries, surgery was delayed
      for up to 24 months in the 12 older patients, an immediate reconstruction was
      done using hamstring tendons in the three youngest patients, and patellar tendon
      treatment was done in the remaining cases. We had only one complication caused by
      the fracturing of the bone plug. The most frequent meniscus injuries were the
      traumatic tears (23 cases), 80% of which were peripheral and longitudinal.
      Whenever possible, the entire meniscus (suture in 4 cases) or the greater part of
      it (economic resection in 19 cases) should be conserved. Despite the satisfactory
      results, the average followup of the meniscal series (26.1 months) is too short a
      period to evaluate thoroughly the deterioration of the joint after a
      meniscectomy.

PMID- 15738811
TI  - Pathologic fractures in children.
AB  - Fractures through bone tumors are often difficult to treat. We reviewed our
      combined experience with this problem in children, as well as the existing
      literature, to formulate management guidelines. For this study, prospective
      databases (1987 to 2002) from three referral centers were screened for pathologic
      fractures occurring under the age of 14 years. One hundred five patients
      presented with fracture through unicameral bone cyst, nonossifying fibroma,
      fibrous dysplasia, aneurysmal bone cyst and osteosarcoma. Seventeen patients were
      excluded. The most common primary locations were the proximal humerus and
      proximal femur. Pathologic fracture through nonossifying fibroma had the best
      outcome; union occurred with nonsurgical treatment in all cases. Unicameral bone
      cyst required surgical treatment to avoid persistence of the cyst and refracture.
      However fracture healing was predictable without surgical treatment. Proximal
      femoral lesions tended to heal in malunion if not fixed surgically. Aneurysmal
      bone cyst required surgical treatment for the lesion to heal and to allow the
      fracture to heal as well. Percutaneous sclerotherapy may be the treatment of
      choice for many of these lesions. Fibrous dysplasia allows fracture healing with
      nonoperative therapy. Progressive deformity requires followup and surgical
      correction. Malignant lesions presenting a pathologic fracture are best managed
      by initial nonoperative therapy during investigation and neoadjuvant therapy when
      possible, followed by definitive treatment.

PMID- 15738810
TI  - Pediatric foot fractures.
AB  - Fractures of the foot in children usually have a good prognosis and generally are
      treated nonoperatively. Displaced fractures of the talus and calcaneus and
      tarsometatarsal dislocations are rare in children and their outcome is generally
      good in the younger child. Older adolescents with these injuries need treatment
      similar to how an adult would be treated for the same injury in order to achieve
      a good result. Foot fractures in children may pose a diagnostic challenge
      particularly in the absence of obvious radiographic changes. Repeated clinical
      examination and judicious use of imaging techniques such as isotope bone scans
      and magnetic resonance imaging are needed to establish a diagnosis. Knowledge of
      the anatomy and significance of accessory bones of the foot and disorders of the
      growing foot skeleton are helpful in managing injuries of child's foot. In this
      study, we review common injuries of a child's foot and include a discussion on
      differential diagnosis.

PMID- 15738812
TI  - The multiply injured child.
AB  - The treatment of multiple traumas in children requires knowledge of common injury
      patterns, incidence, mortality, and the consequences and differences between
      these injuries in children and adult patients. However, epidemiological studies
      concerning pediatric multiple trauma are rare. To address this, data were
      collected and analyzed from 682 multiple trauma patients treated at a Level I
      trauma center. The patients were divided into four age-related groups (< 6 years,
      6-12 years, 13-18 years, and 18-40 years) and were evaluated for trauma
      mechanism, injury distribution, and cause of death. Children aged 6 to 17 years
      mostly were injured as pedestrians and cyclists whereas infants, preschoolers,
      and adults more commonly were injured as car passengers. Pediatric patients
      suffered a significantly higher mortality than adults, with a threefold increased
      risk of death when injured as passengers in car accidents. Injuries to the head
      and the legs were most common. A lower incidence of thoracic (28% versus. 62%),
      abdominal (20% versus 36%), pelvic (22% versus 35%), and upper limb (32% versus
      43%) trauma was observed in children (< 18 years) than in adults (18-40 years).
      Nevertheless, trauma to the thorax, abdomen, and head were associated with a high
      risk of death in all groups. Spinal cord injuries, especially in the cervical
      region, also carried a high risk of mortality (36.8 in the group of patients
      younger than 18 years and 18.9 in the group of patients 18-40 years). Children
      younger than 6 years had the most severe head injuries. The data show that there
      are important differences in incidence, mortality, and injury patterns between
      pediatric and adult patients with multiple traumas.

PMID- 15738813
TI  - The association between hospital volume and total shoulder arthroplasty outcomes.
AB  - The purpose of this study was to evaluate the relationship between increasing
      hospital volume and the following outcomes for total shoulder arthroplasties done
      in the state of New York: length of stay, hospital costs, readmission within 60
      days, revision surgery within 24 months, and death within 60 days. The Statewide
      Planning and Research Cooperative System (SPARCS) database from the New York
      State Department of Health, a census of all hospital discharges in the state, was
      used to evaluate the relationship between hospital volume and outcomes for total
      shoulder arthroplasties for 1996 to 1999. One thousand three hundred seven total
      shoulder arthroplasties were done in New York from 1996 to 1999. Nearly (1/2)
      were done at the five highest-volume hospitals. Middle-volume hospitals has the
      least lengths of stay and hospital costs. Independent of age and comorbidities,
      patients at hospitals with greater volumes of total shoulder arthroplasties were
      at reduced risk of patients being readmitted within 60 days. No other outcomes
      were significantly associated with hospital volume. The finding that greater
      hospital volume decreases risk of readmission may have important public health
      implications, but additional research is needed before implementing policy
      changes.

PMID- 15738814
TI  - Femoral fit predicts radiologic changes, but not clinical results, in Mallory
      head total hip arthroplasties.
AB  - We prospectively studied the clinical and radiologic results of three groups of
      patients: 89 patients who had standard primary total hip replacements; 63
      patients with hip dysplasia who had primary total hip replacements; and 48
      patients who had revision total hip replacements. We studied the differences in
      clinical and radiologic behaviors of a titanium hydroxyapatite-coated stem with
      variations in the tightness of fit of the prosthesis in the femoral canal,
      operative group, stem size, grade of osteoporosis, and morphometric features of
      the femur. The clinical results in all three groups are slightly favorable for
      the standard primary group. Pain relief and stem survival in the three groups
      were similar to those reported in other studies regarding cementless prostheses.
      Nontight femoral fit significantly positively influenced the development of
      cancellous densification; however, the presence of osteoporosis also contributed
      to the formation of cancellous densification. Only tight femoral canal fit
      significantly positively influenced the development of cortical thickening
      independent of other parameters. There was no correlation between clinical
      parameters and the radiologic phenomena in either of the groups.

PMID- 15738815
TI  - The utility of bladder catheterization in total hip arthroplasty.
AB  - The use of a urinary bladder catheter in patients having a total hip arthroplasty
      is controversial. Universal insertion of an indwelling catheter before a total
      hip arthroplasty, and insertion of a catheter postoperatively as necessary, are
      accepted variations of care. From 1993 to 1999, 719 patients having primary,
      unilateral total hip arthroplasties were randomized by surgeons into two groups:
      a group of patients who had universal preoperative insertion of an indwelling
      bladder catheter (340 patients) and an observation group who had catheterization
      as needed (379 patients). Catheterization was required for 295 of these 379
      patients (77.8%). Patients were followed up using a total hip arthroplasty
      database, which recorded all complications. Six patients (1.8%) in the universal
      catheter insertion group had a urinary tract infection develop. Nine patients
      (2.4%) in the catheter as necessary group had a urinary tract infection develop.
      There was no significant difference in incidence of urinary tract infections
      between the two groups. Female gender and increasing age were associated with a
      higher incidence of urinary tract infection in both groups. The average length of
      stay in the hospital for the universal catheter group was 4.8 days, and the
      average length of stay for the catheter as necessary group was 4.5 days. There
      was no significant difference in length of stay in the hospital between the two
      groups. The universal catheter group had an average 590 dollars higher hospital
      cost for their total hip arthroplasties, which was significant. Routine
      preoperative bladder catheterization may not be warranted in patients having
      total hip arthroplasties. Postoperative catheterization as necessary may be more
      cost effective.

PMID- 15738816
TI  - Surgical approach influences periprosthetic femoral bone density.
AB  - Our hypothesis was that the bone mineral density of the proximal femur is altered
      significantly by surgical approach. The change in long-term periprosthetic bone
      mineral density in relation to the alteration of the musculature after the
      anterolateral (Group A) and transgluteal approaches (Group B) has been compared.
      There were 35 hips (30 patients) in Group A and 47 hips (37 patients) in Group B.
      No significant differences were seen between groups with respect to age, gender,
      diaphyseal bone mineral density distribution, or average stem size in a Wilcoxon
      Mann-Whitney test. Measurement of bone mineral density in femoral Gruen zones
      revealed a significant bone loss in Group B compared with Group A in the
      multivariate analysis, which was confirmed by univariate post hoc tests in Zones
      I, II, VI, and VII (multiple significance according to Bonferroni-Holm's
      procedure). The functional outcome, however, showed no significant differences
      between the two groups postoperatively. A potential reason for the bone mineral
      density shift might have been a redistribution of the musculoskeletal loading
      across the hip after a transgluteal, compared with an anterolateral, surgical
      approach. A difference in the muscular damage caused by the two surgical
      approaches seems to have a significant influence on the long-term bone loss.

PMID- 15738817
TI  - Fixation of revision implants is improved by a surgical technique to crack the
      sclerotic bone rim.
AB  - Revision joint replacement has poorer outcomes compared with primary joint
      replacement, and these poor outcomes have been associated with poorer fixation.
      We investigated a surgical technique done during the revision operation to
      improve access from the marrow space to the implant interface by locally cracking
      the sclerotic bone rim that forms during aseptic loosening. Sixteen implants were
      inserted bilaterally by distal femur articulation of the knee joint of eight
      dogs, using our controlled experimental model that replicates the revision
      setting (sclerotic bone rim, dense fibrous tissue, macrophages, elevated
      cytokines) by pistoning a loaded 6.0-mm implant 500 microm into the distal femur
      with particulate PE. At 8 weeks, one of two revision procedures was done. Both
      revision procedures included complete removal of the membrane, scraping,
      lavaging, and inserting a revision plasma-spray Ti implant. The crack revision
      procedure also used a splined tool to circumferentially locally perforate the
      sclerotic bone rim before insertion of an identical revision implant. Superior
      fixation was achieved with the cracking procedure in this experimental model.
      Revision implants inserted with the rim cracking procedure had a significantly
      higher pushout strength (fivefold median increase) and energy to failure (sixfold
      median increase), compared with the control revision procedure. Additional
      evaluation is needed of local perforation of sclerotic bone rim as a simple bone
      sparing means to improve revision implant fixation and thereby increase revision
      implant longevity.

PMID- 15738818
TI  - A bioresorbable molding mesh for impaction grafting revision hip surgery.
AB  - Impacted morselized allografts are used to treat bone loss in revision surgery.
      This technique depends on adequate mechanical support of the graft. Metal support
      devices function well, but there are disadvantages associated with the use of
      steel meshes. In this cadaveric, surgical simulation model we investigated the
      surgical and mechanical suitability of a bioresorbable molding mesh for use in
      impaction grafting revision surgery. Surgical feasibility was assessed, and
      mechanical deformation of the mesh during the surgical procedure and
      postoperative cyclic loading of the specimens were measured with strain gauges.
      All meshes were surgically usable. The exterior surface deformation of the meshes
      during the surgical procedure and postoperative mechanical loading did not exceed
      4500 microm/m, although the meshes were not damaged in a four-point bending test
      in which deformations higher than 19,000 microm/m were reached. Therefore,
      results of this study suggest that this type of bioresorbable mesh seems to have
      sufficient initial mechanical properties to warrant additional preclinical in
      vivo study.

PMID- 15738819
TI  - Variables affecting initial stability of impaction grafting for hip revision.
AB  - Impaction grafting allows restoration of bone stock in hip revision, but there
      are reports of massive early subsidence. The aim of this study was to determine
      prognostic factors for stem and cup migration in a group of 56 consecutive
      patients followed up from 1 to 5 years. Cup and stem migration was correlated
      with 13 predictors including stem design, stem positioning, femoral anatomy,
      patient characteristics, and bone graft density. All migration occurred mainly
      during the first 3 months after surgery. Stem alignment changed by an average of
      4.8 degrees . Fifty percent of the change in stem alignment was explained by four
      variables: age, femoral diameter, stem design, and density of the graft at the
      tip of the stem. Stem subsidence averaged 2.7 mm, and cup migration averaged 3.0
      mm. None of the predictors explained the wide variation of migration of the cup
      or distal migration of the stem. It may be necessary to determine implant
      stability at the time of surgery.

PMID- 15738820
TI  - Femoral revision with impaction grafting and a collarless, polished, tapered
      stem.
AB  - Femoral impaction allografting has been done with and without variations of the
      original description. The purpose of this study was to review Harris hip scores,
      radiographs, and complications in patients in whom we used the original technique
      without significant modifications. Preoperative and postoperative hip scores and
      radiographic data were available at a mean of 4.7 years for 43 of 44 hips that
      had femoral component impaction allografting with a collarless, polished, tapered
      stem. Bone stock was classified according to the Endo-Klinik classification.
      Survivorship, using femoral reoperation for symptomatic aseptic loosening as the
      end point, was 97%. The mean Harris hip score improved from 45 to 90 with pain
      improved in all. Subsidence 4 mm and greater occurred in only two hips, but
      neither has been revised. One hip was revised for mechanical loosening after a
      fall on the surgically treated extremity 6 years after surgery. Complications
      included three intraoperative fractures, one femoral fracture recognized
      postoperatively, one trochanteric nonunion, and one dislocation. Femoral
      component revision with impaction allografting and a collarless, polished,
      tapered stem was reproducible and improved Harris hip scores in patients with
      aseptic femoral component loosening and bone loss at a mean of 4.7 years after
      surgery.

PMID- 15738821
TI  - Preoperative tibiofemoral angle predicts survival of proximal tibia osteotomy.
AB  - A prospective group study was done to clarify whether perioperative variables
      such as preoperative and postoperative tibiofemoral angles influence the
      survivorship of proximal tibia osteotomy as measured by conversion to
      arthroplasty and patient dissatisfaction. The results of 93 proximal tibial
      osteotomies in 82 consecutive patients with medial compartment osteoarthrosis
      were followed up for a mean of 10.9 years. All data were analyzed by the Kaplan
      Meier survivorship method and the multivariate Cox proportional hazards model.
      Only the preoperative tibiofemoral angle was a predictor of conversion to
      arthroplasty and patient dissatisfaction. The ideal prognostic cutoff angle was 9
      degrees or less varus. Increasing the preoperative varus alignment 1 degrees
      would result in a 1.2 (95% confidence intervals, 1.02-1.50) times higher risk of
      conversion to a total knee arthroplasty and a 1.5 (95% confidence intervals, 1.27
      1.76) times higher chance of patient dissatisfaction. Factors such as age,
      gender, body mass index, Ahlback's classification, and postoperative tibiofemoral
      angle were not significant. We think that proximal tibial osteotomy should be
      considered for patients with medial compartment osteoarthrosis and a preoperative
      varus alignment of 9 degrees or less, whereas arthroplasty is a more suitable
      alternative for patients with preoperative varus alignment greater than 9
      degrees.

PMID- 15738822
TI  - A meta-analysis of patellar replacement in total knee arthroplasty.
AB  - From individual randomized studies it is unclear whether the patella should be
      replaced during total knee replacement. We did a meta-analysis to provide
      quantitative data to compare patellar resurfacing with nonresurfacing during
      total knee arthroplasty. Only randomized, controlled trials reported between
      January 1966 and August 2003 comparing patellar replacement with patella
      retention were included for a total of 12 studies. Two reviewers assessed trial
      quality and extracted data from papers. The outcomes identified were reoperations
      for patellar problems, anterior knee pain, knee scores, stair climbing, and
      patient satisfaction. The resurfaced patella performed better, and we found an
      increased relative risk (defined by the ratio of the risk of the event in the
      resurfaced group on the risk of the event in the nonresurfaced group) for
      reoperation, for significant anterior knee pain, and for significant pain during
      stair climbing when the patella was left unresurfaced. No differences were
      observed between the two groups for International Knee Society function score,
      Hospital for Special Surgery score, and for patient satisfaction. Despite these
      general findings, forming a definitive conclusion is difficult because many
      confounding factors, such as component design, surgeon experience, and technical
      aspects of the surgery, might influence the result in a patient.

PMID- 15738823
TI  - Real in vivo kinematic differences between mobile-bearing and fixed-bearing total
      knee arthroplasties.
AB  - We did an in vivo fluoroscopic study comparing the sagittal plane kinematics of
      mobile-bearing and fixed-bearing total knee arthroplasties in a unique group of
      patients. These patients were part of a larger bilateral randomized controlled
      outcome trial with each patient having received both types of total knee
      arthroplasties. Invited patients did three exercises with each of their different
      knee replacements; extension against gravity, flexion against gravity, and a step
      up. These exercises were recorded using video fluoroscopy, and a series of still
      digital images over the flexion range were retrieved. The relationship of patella
      tendon angle to knee flexion angle for each patient was derived. The patella
      tendon angle to knee flexion angle of the mobile-bearing knee behaved in a linear
      manner more closely replicating the normal knee, whereas the fixed-bearing knee
      behaved in a nonlinear, more variable manner. This pattern of results was similar
      for all three exercises with each patient having one knee replacement that
      behaved differently in the sagittal plane when compared with their other knee
      replacement. These kinematic differences may explain the clinical differences
      observed in the randomized controlled trials that compared these two total knee
      arthroplasties.

PMID- 15738824
TI  - Infection in massive bone allografts.
AB  - We studied a series of 945 patients who received cadaveric allografts implanted
      for nonpelvic bone or soft tissue tumor lesions since 1971. We specifically were
      interested in the role of infection in the graft process, and, more specifically
      its history, frequency, and affect on outcome. Primary infections (not related to
      reoperations for nonunions or fractures of the graft) occurred in 75 patients
      (7.9%), and an additional 46 patients had infections related to reoperations,
      increasing the total number of patients with infections to 121 (12.8%). The
      highest frequency of infection occurred in patients with soft tissue tumors,
      radiated sites, Musculoskeletal Tumor Society Stage IIB tumors, or surgeries
      consisting of an allograft arthrodesis. Most of the infected grafts failed;
      however, none of the patients died. One patient had hepatitis C develop, and one
      patient became HIV positive after receiving the virus from a blood transfusion. A
      comparison with other series of surgically treated patients, including those
      receiving metallic devices, suggests that the infection rate may be related to
      the surgery or the graft's immunologic resistance, rather than the graft. The
      problem of infection is a major issue for tumor surgeons. Suggestions regarding
      how to decrease the frequency of this complication are presented.

PMID- 15738825
TI  - Subtrochanteric fixation stability depends on discrete fracture surface points.
AB  - Fixation of subtrochanteric femur fractures may present complications, including
      malunion, delayed union, or nonunion, and is thought to be related to early
      fracture stability. To examine the initial stability of subtrochanteric fracture
      fixation, we investigated construct stiffness, interfragmentary gaps, and overall
      and point-wise interfragmentary motion (ie, axial and shear displacements) in
      synthetic composite femurs fixed with a cephalomedullary nail or condylar blade
      plate. Simulated stable and unstable subtrochanteric femur fractures were created
      in composite femurs, anatomically reduced, fixed with either a long Gamma nail or
      a blade plate, and subjected to combined axial, bending, and torsional loading.
      The long Gamma nail group consistently showed greater displacement magnitudes
      than the blade plate group; these differences included axial and shear
      displacement magnitudes in the stable fracture group and shear displacement
      magnitudes in the unstable fracture group. Overall differences in fixation
      stability were dependent on discrete points around the periphery of the
      contiguous fracture surfaces, especially in the unstable fracture group. These
      differences in interfragmentary motion patterns between implant constructs were
      detected despite the lack of difference in combined axial, bending, and torsional
      construct stiffness or initial interfragmentary gap.

PMID- 15738826
TI  - Biodegradable implants for Pipkin fractures.
AB  - The current study was designed to clarify whether biodegradable poly-L/DL lactide
      pins provide an operative alternative for fixation of Pipkin fractures. Nine
      patients with Pipkin fractures (one with Pipkin Type I, one with Pipkin Type II,
      and seven with Pipkin Type IV fractures) were treated surgically between 1996 and
      2002. In all patients, the femoral head fractures were fixed with biodegradable,
      2.7-mm and 2.0-mm polylactide pins. Eight patients were followed up for an
      average of 54.2 months. One patient died before the final followup. Eight
      fractures healed uneventfully. In one patient, a persisting femoral head defect
      led to posttraumatic arthritis requiring insertion of a femoral endoprosthesis at
      1 year. The average range of motion of the affected hips of all patients at
      followup was 109 degrees -0 degrees -0 degrees in flexion and extension. External
      and internal rotation averaged 37 degrees -0 degrees -29 degrees . One patient
      had Brooker Grade I heterotopic ossification develop, and another had a Grade II
      heterotopic develop. Merle d'Aubigne and Postel ratings showed two excellent and
      five satisfactory results (average score, 13.1). Adverse effects from the
      polylactide implants were not observed. Pipkin fractures can be fixed
      successfully with biodegradable polylactide pins.

PMID- 15738827
TI  - Primary echinococcus infestation of the bone and muscles.
AB  - Hydatid diseases of the bone and muscles are rare, generally are incurable, and
      have a high level of recurrence. We attempted to ascertain whether the recurrence
      rate decreased in patients with hydatid disease infestation of the bone and
      skeletal muscle who were treated with current surgical techniques and
      antihelminthic chemotherapy, and whether the outcomes for bone infestation were
      different when compared with outcomes for muscular infestation. We
      retrospectively reviewed 15 patients with hydatid disease of the bone (eight
      patients) and muscle (seven patients). The average followup was 30 months (range,
      6-69 months). Recurrence was observed in four patients with bone involvement. No
      patient with muscle involvement had a recurrence after excision. Hydatid disease
      of the bone often is recurrent and progressive despite using advanced diagnostic
      studies, improved surgical techniques, and newly developed antihelminthic drugs.
      The disease status also was not as good as for patients with bone lesions when
      compared with patients with muscular lesions.

PMID- 15738829
TI  - Preliminary validation of clinical assessment for deep vein thrombosis in
      orthopaedic outpatients.
AB  - The purpose of our study was to determine if a previously published clinical
      decision rule designed to estimate the probability of proximal deep vein
      thrombosis in outpatients is valid when applied exclusively to outpatients with
      musculoskeletal disorders. We also sought to determine whether probability
      estimates differed for patients with or without trauma, fracture, or recent
      orthopaedic surgery. Data collected from outpatients with surgical and
      nonsurgical musculoskeletal disorders (n = 464) were extracted from the datasets
      of three previously published studies done on heterogeneous groups of patients (n
      = 3424). Followup for all patients was 3 months. Testing of all patients for
      thromboembolic disease was done using validated diagnostic procedures.
      Probability estimates for orthopaedic outpatients were consistent with estimates
      from published studies. The proportion of patients who had venous thromboembolism
      was 5.6% (95% confidence interval, 3.5-8.7%) for the low probability group, 14.1%
      (95% confidence interval, 8.6-22.4%) for the moderate probability group, and
      47.4% (95% confidence interval, 35.3-60%) for the high probability group.
      Validity estimates for patients with and without recent trauma, surgery, or
      fracture differed, but not dramatically. The validity of the clinical decision
      rule as applied to outpatients with musculoskeletal disorders was supported.

PMID- 15738828
TI  - Selective retention of bone marrow-derived cells to enhance spinal fusion.
AB  - Connective tissue progenitors can be concentrated rapidly from fresh bone marrow
      aspirates using some porous matrices as a surface for cell attachment and
      selective retention, and for creating a cellular graft that is enriched with
      respect to the number of progenitor cells. We evaluated the potential value of
      this method using demineralized cortical bone powder as the matrix. Matrix alone,
      matrix plus marrow, and matrix enriched with marrow cells were compared in an
      established canine spinal fusion model. Fusions were compared based on union
      score, fusion mass, fusion volume, and by mechanical testing. Enriched matrix
      grafts delivered a mean of 2.3 times more cells and approximately 5.6 times more
      progenitors than matrix mixed with bone marrow. The union score with enriched
      matrix was superior to matrix alone and matrix plus marrow. Fusion volume and
      fusion area also were greater with the enriched matrix. These data suggest that
      the strategy of selective retention provides a rapid, simple, and effective
      method for concentration and delivery of marrow-derived cells and connective
      tissue progenitors that may improve the outcome of bone grafting procedures in
      various clinical settings.

PMID- 15738830
TI  - Improving the diagnostic process for deep vein thrombosis in orthopaedic
      outpatients.
AB  - Prompt diagnosis of proximal lower extremity deep vein thrombosis in outpatients
      is critical because of the risk of pulmonary embolism. Our purpose was to
      determine the accuracy of orthopaedists' clinical decisions regarding the
      diagnosis of proximal deep vein thrombosis in outpatients. A nationally
      representative random sample of 2300 orthopaedists received a survey of six
      clinical vignettes. They were asked to estimate the probability of proximal lower
      extremity deep vein thrombosis using defined criteria and to specify their
      planned diagnostic tests. A clinical decision rule and evidence-based diagnostic
      test recommendations from the general literature served as the gold standard for
      comparison. Six-hundred seventy-six (29%) surgeons completed the survey. The
      orthopaedists' planned diagnostic tests differed from the gold standard, but
      these differences varied depending on the probability of deep vein thrombosis.
      For the moderate and high risk vignettes, the diagnostic test recommendations
      agreed with the gold standard approximately 70% of the time. With the exception
      of gender, no differences were found between respondents and nonrespondents.
      Orthopaedists' approach to the diagnosis of deep vein thrombosis in outpatients
      potentially could be improved by applying a clinical decision rule and current
      evidence on diagnostic test usage.

PMID- 15738831
TI  - Lymphoma masquerading as infection.
AB  - During surgical training, medical students and residents constantly are reminded
      to culture every suspected tumor and send tissue for pathologic evaluation for
      every suspected abscess. A diagnosis of cancer can be missed easily if this
      procedure is not followed, delaying the diagnosis and possibly adversely
      affecting the patient's prognosis. The confusion also may be compounded by a
      sterile abscess, positive culture results or a negative biopsy specimen.
      Therefore it is imperative to do a biopsy and a culture on any suspect lesion. An
      additional workup and possible biopsy may be warranted for a nonhealing wound
      that has been treated appropriately. The cases of three patients with lymphoma
      that were treated as infectious processes are presented. In all three instances,
      the appropriate treatment was delayed because of a delay in diagnosis.

PMID- 15738832
TI  - Chronic knee pain in a 21-year-old woman.

PMID- 15738833
TI  - [Should we operate asymptomatic carotid stenoses?].

PMID- 15738834
TI  - [Who should treat smokers?].

PMID- 15738835
TI  - [Drug addiction and cardiovascular pathologies].
AB  - Drug addiction which entails cardiovascular risks unknown or misknown to
      physicians, currently involves an increasing number of miscellaneous drugs,
      existing in manifold forms. There appears to be no bounds on the way of intake.
      All territories of the body may be affected with more or less severity. In young
      people, the cardiac, coronary, cerebral and peripheral vascular systems are
      generally involved. Two illicit drugs, cannabis and cocaine, showing a permanent
      increase in misuse, prevail. This drug addiction comes along with intercurrent
      pathologies which have their own vascular toxicity, especially HIV infection.
      Moreover, the advent of new illicit substances emphasizes the complexity of the
      clinical presentations. These complex situations have a real social and medical
      impact. We are currently in a phase of permanently increasing risk of
      cardiovascular complications. The pathophysiological mechanisms involved are
      intertwined and complicated by the frequent association of polytoxicomania or by
      the effects excipients added to these drugs: direct vascular toxicity, angeitis,
      arterial and venous thrombosis. Arsenic, a common component of these drugs, is
      also found in cigarettes; arsenic toxicity mainly affects the lower limbs.
      Treatment of these complications is non-specific; the ideal solution being
      weaning which, unfortunately in this peculiar population of patients, may entail
      serious complications due to the misuse of substitution products.

PMID- 15738836
TI  - [Peripheral arterial disease: what management practices for general
      practitioners?].
AB  - OBJECTIVE: The purpose of this study was to analyze the results of the ATTEST
      study in order to evaluate general medicine management practices for peripheral
      arterial disease (PAD). Our analysis was based on the guidelines for good
      practice which recommend measurement of the systolic pressure index (SPI), search
      for other localizations of atherothrombosis, treatment of risk factors including
      smoking, walking exercises, and long-term prescription of anti-platelets.
      METHODS: ATTEST is a cross-sectional multicentric observational epidemiologic
      study conducted in metropolitan France. The study has recruited 8.475 analyzable
      patients with symptomatic PAD alone (3811 patients) or associated with other
      atherothrombotic localizations (2416 patients) or other cardiovascular diseases
      (2248 patients). These patients were followed by 3020 physicians. The current
      analysis thus included 6227 patients (81.2% men, 18.8% women, mean age 67.2
      years), including 78.8% who had reached the stage of intermittent claudication.
      Risk factors included current or past smoking (61%), hypercholesterolemia
      (66.3%), hypertension (63.1%) and diabetes mellitus (26%). RESULTS: Arterial
      duplex Doppler exams of the lower limbs were performed in 91.2% of the patients
      but measurement of the SPI for diagnostic purposes had been performed in only
      17%. The majority (85.8%) of the patients with proven coronary artery disease or
      cervico-encephalic involvement had had an ECG and 69.3% had had a duplex Doppler
      of the supra-aortic trunks. Smoking continued in 39% of the patients and an aid
      to cease smoking had been prescribed for only 7% of the patients who were non
      smokers for less than one year. Nearly two-thirds of the patients analyzed had
      received advice concerning physical activities. Finally, anti-platelets had been
      prescribed for 92.2% of the patients. CONCLUSIONS: The general practitioner plays
      a crucial role in the diagnosis and treatment of PAD. Although measurement of the
      SPI is recommended as an early diagnostic tool and for evaluation of severity, it
      had been performed in less than one-third of the patients. Search for another
      localization of atherothrombosis had been performed in more than half of the
      patients. The physicians generally delivered advice on physical exercise and
      prescribed anti-platelets. The fight against smoking was however largely
      insufficient. The results of this study warrant further optimization of the
      collaboration between general practitioners and vascular disease specialists.

PMID- 15738837
TI  - [Comparative analysis of lymphoscintigraphy between lipedema and lower limb
      lymphedema].
AB  - Lipedema is characterized by bilateral enlargement of the legs due to abnormal
      deposition of fat tissue from pelvis to ankles. It is seen most frequently in
      obese women. Lipedema appears to be a distinct clinical entity but may be
      confounded with lymphedema. AIM OF THE STUDY: To analyze and to compare between
      lipedema and lymphedema the qualitative and quantitative aspects of
      lymphoscintigraphy. METHODS: Fifteen women with lipedema were recruited. Mean age
      of onset of lipedema was 31.5 +/- 15 years. Body mass index was 35.1 +/- 7.9
      kg/m2, 13 women were obese. Lipedema was compared to 15 cases of primary
      lymphedema (women: 13, men: 2) of the lower limbs (unilateral: 13, bilateral: 2),
      with a mean age at onset of 28.7 +/- 12.6 years. Lymphoscintigraphy of the lower
      limbs with morphologic (visualization of inguinal lymph nodes) and kinetic (half
      life, lymphatic speed of the colloid) studies was performed in all cases.
      RESULTS: Absence of visualization of inguinal lymph nodes was observed in 14/15
      cases of lymphedema and in 1/15 cases of lipedema (p<0.001). In the 13 cases of
      unilateral lymphedema, colloid half-life was higher in the pathologic limb than
      in the controlateral limb (230 +/- 92 vs 121 +/- 36 minutes, p<0.01) and
      lymphatic speed of the colloid was slower (6.91 +/- 0.86 vs 8.16 +/- 1.02 cm/min,
      p<0.001). The two patients with bilateral lymphedema had an increased half-life
      and decreased lymphatic speed of the colloid. Colloid half-life was significantly
      higher in lipedema than in controlateral limbs of lymphedema (154 +/- 23 vs 121
      +/- 36 minutes, p<0.01) with no difference in lymphatic speed of the colloid.
      Colloid half-life was significantly higher in lymphedema than in lipedema (230 +/
      92 vs 154 +/- 23 minutes, p<0.01) and the lymphatic speed of the colloid was
      slower (6.91 +/- 0.86 vs 8.10 +/- 0.45 cm/min, p<0.001). CONCLUSION: Lower limb
      lymphoscintigraphy showed lymphatic insufficiency in lipedema without morphologic
      abnormality as seen in lymphedema. Lymphoscintigraphy is not indispensable but is
      a useful tool when diagnosis is doubtful. Treatment is difficult and may include
      weight loss and possible surgery.

PMID- 15738838
TI  - [Superficial thrombophlebitis in non varicose veins of the lower limbs. A
      prospective analysis in 42 patients].
AB  - Recent publications allow better understanding of superficial thrombophlebitis
      (ST) of the lower limb veins. However ST occurring in non varicose veins (NVV)
      and those occurring in varicose veins (VV) are seldom distinguished in
      literature. AIMS OF THE STUDY: 1) To estimate the potential gravity of ST
      occurring in NVV by putting a figure on the frequency of associated deep venous
      thrombosis (DVT) and symptomatic pulmonary embolism (PE); 2) to identify some
      risk factors (thrombophilia, systemic disease, thromboembolic events); 3) to
      assess the different types of thromboembolic recurrent events after superficial
      thrombophlebitis (TRST) and identify the risk factors for recurrence. MATERIAL
      AND METHOD: Forty-two cases of ST occurring in NVV were included consecutively
      and prospectively in this series; TRST possible risk factors were evaluated.
      Patients were assessed at 1 month and followed up to 3 years. Isolated ST was
      treated with low-molecular-weight heparin at prophylactic dosage from 15 to 21
      days and with elastic compression. RESULTS: 1) A DVT was combined in 12 cases
      (28.6%) located in the calf (n=9) or in the femoro-politeal axis (n=3). One
      symptomatic PE occurred confirmed by ventilation-perfusion lung scan; 2) The risk
      factor investigations identified a neoplasm in 2 patients (4.8%), a non neoplasic
      systemic disease in 4 (9.5%) and a thrombophilia in 20 patients. The most
      frequent thrombophilia was the heterozygous mutation of coagulation factor V
      (Leiden); 3) All patients were assessed at 1 month with a clinical examination
      and Duplex Scanning. We did not identify either new DTV, PE or extension of the
      previous DVT; 4) 17 TRST were identified in 13 patients. Three patients had 2
      recurrences; one patient presented a TRST located at 2 different sites. In total
      8 new ST and 9 DVT were identified. DISCUSSION: The analysis of the literature
      shows that early complications or combinations (DVT and PE) occur with the same
      prevalence in NVV and VV groups. A risk factor was identified in 62% of patients
      in this series (thrombophilia was the most common) and TRST were statistically
      more frequent in this series than in groups of ST occurring in VV we had
      previously analyzed. A post-thrombotic syndrome and a DVT associated with the ST
      were identified as statistically significant risk factors for recurrence.
      CONCLUSION: ST occurring in NVV, although representing 5 to 10% of all ST, is
      seldom reported in the literature. Like ST occurring in VV, they have a potential
      gravity (associated DVT and PE). However these two diseases should be
      distinguished. A risk factor is more often identified and TRST are more frequent
      in the group of ST occurring in NVV. We advise active management of these
      thromboses including screening for a risk factor, the implementation of measures
      for preventing venous thrombosis recurrence and patient follow-up.

PMID- 15738840
TI  - [A view of the profession: vascular physician].

PMID- 15738839
TI  - [Endoluminal dilatation of symptomatic atheromatous stricture of the carotid
      bifurcation].

PMID- 15738841
TI  - [A plea in favor of xenografting].

PMID- 15738842
TI  - [The risk of biliary ductal injury during laparoscopic cholecystectomy].
AB  - The incidence of iatrogenic injuries of the bile ducts has increased
      significantly since laparascopic cholecystectomy became the "gold standard" in
      the treatment of cholelithiasis. The incidence of major biliary ductal injury
      ranges from 0.25% to 0.74%, and of minor injury from 0.28% to 1.7%. The cause of
      the injury is not always clearly identifiable. In more than half the cases, the
      injury occurs during maneuvers to isolate the cystic duct or to free the
      gallbladder from the common bile duct. These maneuvers may be more difficult and
      consequently more dangerous when there is significant inflammation as may be seen
      in acute cholecystitis, or in case of obesity, cirrhosis with portal
      hypertension, previous surgery with peritoneal adhesions, or anatomic variations
      of the hepatic pedicle. Pre-operative evaluation of clinical risk factors should
      be coupled with intra-operative caution and instrumental evaluation. The increase
      in frequency of iatrogenic biliary injuries can not be attributed simply to the
      inexperience of the surgeon or the learning curve as was initially suggested.
      Many injuries are due, rather, to the surgeon's failure to respect basic
      technical rules, long established for open cholecystectomy and which should not
      be modified for the laparoscopic technique. While routine cholangiography does
      not offer complete protection from iatrogenic ductal injuries, it is essential to
      visualize the biliary tract whenever a lesion of the ductal system is clearly
      identified or even suspected. In such cases, facility with the technique of
      intraoperative cholangiography and a knowledge of the radiological anatomy of the
      biliary tree are essential for an accurate and complete intraoperative evaluation
      of the biliary injury. Finally, in the presence of acute or chronic inflammation
      or other factors for technical difficulty (obesity, cirrhosis, previous surgery,
      anatomic variations, intraoperative bleeding), the surgeon must not hesitate to
      consider conversion to an open surgical approach. In such complicated cases, even
      the open approach is not a guarantee against biliary injury; there is no
      substitute for experience and caution in biliary surgery.

PMID- 15738843
TI  - [The treatment of biliary stenosis with metallic stents: the need for
      multidisciplinary decision making].
AB  - A patient presented with a cholangiocarcinoma of the common bile duct; it was
      initially considered unresectable leading to the placement of the metallic stent
      whose upper end extended beyond the convergence of the hepatic ducts. The
      metallic biliary stent became obstructed and so encrusted as to be unremovable;
      the patient required a left hepatectomy with resection of the stent and the
      biliary convergence in addition to a pancreatoduodenectomy in order to resect his
      primary lesion This difficult situation emphasizes that, whenever there is doubt
      as to the resectability of a biliary lesion, the decision to place a metallic
      stent should be the fruit of a thorough medico-surgical discussion; where there
      is any doubt, a plastic stent which is more easily removable should be placed.

PMID- 15738845
TI  - [Laparoscopic treatment of ventral hernias].

PMID- 15738846
TI  - [How I do it: Habib's technique for hepatic resection].

PMID- 15738844
TI  - [Laparoscopic treatment of ventral hernias].
AB  - The use of mesh in incisional hernia repair has reduced the rate of hernia
      recurrence. Laparoscopic placement of mesh is a promising alternative to the
      classical open approach. Recent studies involving large numbers of patients have
      shown the laparoscopic approach to be feasible in 95% of cases; the incidence of
      postoperative complications was low and hernia recurrence occurred in 3-5% at
      three years. Several retrospective studies and one randomized study comparing
      open versus laparascopic ventral hernia repair suggest that the laparoscopic
      repair yields better results (fewer postoperative complications and lower
      recurrence rate) than the classical open approach.

PMID- 15738847
TI  - [Migration of a mesh prosthesis from hernia repair into the colonic lumen].

PMID- 15738848
TI  - [Hydatid cyst of the liver].
AB  - Hydatid cyst of the liver is a parasitic disease caused by Echinococcus
      granulosus. The principal complications are infection, biliary duct fistula, and
      rupture into the peritoneum or chest. Diagnosis has become easier with advances
      in ultrasonic imaging and CT scanning. Surgery remains the most effective
      treatment but postoperative complications arise in 30% of cases, particularly
      when the surgical approach is conservative. Radical surgical approaches give
      better results and should be used in most cases. Biliocutaneous fistula and
      infection of the residual cavity are the most common postoperative complications
      and result in prolonged hospitalization and excess costs. New therapeutic
      strategies incorporate endoscopic, percutaneous, and medical therapies with
      surgery and have allowed an improvement in morbidity and mortality due to hydatid
      cysts of the liver. Until immunization becomes a possibility, preventive measures
      are necessary to avoid disease recurrence.

PMID- 15738849
TI  - [In the name of the law: chronicle of the daily ordinary life of a hospital].

PMID- 15738850
TI  - [106th French Congress of Surgery. Paris, France, October 7-9, 2004].

PMID- 15738851
TI  - [Multilobular liver abscess due to Streptococcus bovis].

PMID- 15738852
TI  - [Hyperthymic and depressive temperaments study in controls, as a function of
      their familial loading for mood disorders].
AB  - Since the two last decades, many authors have broadened the scope of mood
      disorders to include a larger bipolar spectrum which encompasses the sub
      affective conditions, including temperaments. According to this view, the latter
      conditions represent milder or alternative expressions of the classic bipolar
      episodes. In successive elaborations, Akiskal et al. hypothesized a complex
      multicausal approach to bipolar disorder, and studied temperamental
      dysregulations, which could serve as risk factors for major episodes. Until
      recently, there have been several studies of patients populations, little is
      known in control populations. The aim of this report is to compare the rates of
      three affective temperaments (hyperthymic: TH; depressive: TD; irritable: TI) in
      non-ill subjects with different risk for mood disorders. (The cyclothymic
      temperament is studied as part of another report). METHODS: We recruited 185
      individuals from: a) staff hospital; b) sibling of patients suffering from
      bipolar disorder, type I. Twenty subjects were excluded: 7 suffered from personal
      affective trouble; 12 exhibited cyclothymic traits; and one had familial
      schizophrenia. In the 165 remaining subjects, the temperamental characteristics
      were assessed by mean of the Akiskal and Mallya's criteria (1987, semi-structured
      interviews for affective temperaments, TH, TD, TI). Then, the population of
      controls was divided in 3 groups as a function of the familial loading for
      affective disorder and bipolar disorders: the first subgroup (AFN) was free of
      any antecedent ("super-normal controls", n=99); the second subgroup (AFP) had
      familial antecedents at the first or second degree (normal controls but at risk
      for affective disorder, n=33); the third subgroup (FBP) was composed of the
      siblings of bipolar I patients (subjects at high risk, n=33). Statistical
      procedures included standard and non-parametric methods: means standard
      deviation, Fisher's test, Mann-Whitney' and Kuskall-Wallis' tests, Spearman's
      correlation coefficient. As described by Placidi and collaborators (12), we also
      used the Z-score (temperamental score strictly higher than the second positive
      standard deviation: m + 2 sd). RESULTS: The general demographic characteristics
      show a higher frequency of women (p=0.02) but a similar mean age (p=0.296, NS)
      among the groups. The mean scores of the TH and TD are strongly and negatively
      correlated (Rho coefficient=- 0.397, p=0.01), exhibiting the internal coherence
      of the responses. The comparison of the temperamental characteristics among the 3
      groups exhibits significant differences for the TH and TI (p=0.003). The mean
      scores are respectively: for the TH, 9.16 4.18 in AFN, 8.33 4.11 in AFP, and
      12.16 5.28 in FBP; and for the TI, 8.94 2.25 in AFN, 9.39 2.63 in AFP, and 10.84
      2.76 in FBP. Conversely, the TD scores do not significantly differ: 6.01 3.27 in
      AFN, 6.76 4.34 in AFP, and 7.94 5.28 in FBP. Beyond these first pass results, we
      also considered the distribution of the subjects as function of the Z-score and
      the different groups. We found that hyperthymic traits were almost exclusively
      among the FBP: 15.1% vs 3.0% in the other groups. For the TD, expressed in mean
      scores, the groups at risk for affective disorders (AFP and FBP) clearly display
      a percentage of subjects with a more substantial Z-score than the frequencies
      observed in the AFN: respectively 12.1%, 18.1% and 4.0% for the TD. Concerning
      traits of all three temperaments, as function of the demographic variables and
      the Z-score, they are generally predominant in males; however, the TH is more
      frequent in males only in the AFP and FBP groups (respectively: 8.3% vs none;
      21.4% vs 10.5%). The TD is more prevalent among females in AFP and FBP
      (respectively: 8.3% vs 14.3%; 21.1% vs 14.8%). CONCLUSION: Our results clearly
      show temperamental dysregulations in the subjects at risk for affective
      disorders: (1) the levels of all three affective temperaments under study are
      significantly higher in subjects at risk for affective disorder, as compared to
      individuals free of a family antecedent; (2) the depressive temperament is
      prevalent in both AFP and FBP, whereas the hyperthymic is specific for FBP. As
      for Akiskal's model on the multicausal origin of the mood disorders, our data
      supports temperamental dysregulation as an important familial genetic factor in
      the vulnerability to manic depressive episodes. We further posit that such
      temperaments--more specifically, the hyperthymic--could serve as proximal
      phenotypes for full-blown bipolar disorder.

PMID- 15738853
TI  - [The Fear of Negative Evaluation scale (FNE): psychometric properties of the
      French version].
AB  - BACKGROUND: The Fear of Negative Evaluation scale (FNE: Watson and Friend, 1969)
      is the measure most commonly used to determine the degree to which people
      experience apprehension at the prospect of being negatively evaluated. Although
      the development of the FNE preceded the inclusion of social anxiety disorder (or
      social phobia) in the diagnostic classification system, it is widely used as a
      measure of cognitive symptoms because the feature tapped by this measure is at
      the core of recent cognitive models of social-anxiety. According to these models,
      socially anxious individuals divide their attention between the internal
      representations of their social self (negative images and "felt sense") and
      external cues that could be taken as a sign of negative evaluation by others. The
      FNE was validated in a student and patient population in English speaking
      countries. The English version demonstrates adequate empirical validity. It shows
      excellent internal consistency and one-factor structure. Test retest reliability
      is satisfying. It is proved to be sensible to change after treatment. It is well
      correlated with other measures of social anxiety demonstrating good convergent
      validity. However, divergent and discriminate validity have been a subject of
      controversy. The aim of the present study was to assess the psychometric
      properties of the French version of the FNE in order to obtain a valid instrument
      measuring the cognitive component of social anxiety. METHOD: The social anxiety
      group consisted of 88 patients referred to our clinic for cognitive-behavioural
      group therapy. All met ICD-10 criteria for social phobia (generalized subtype) as
      determined by the Composite International Diagnostic Interview (social phobia
      section). Additional axis-I diagnostic information was obtained using the Mini
      International Neuropsychiatric Interview (MINI: Lecrubier et al., 1997) for ICD
      10. The non-patient control group consisted of 80 participants who didn't respond
      to social anxiety CIDI criteria. All participants were rated by the assessor on
      the Liebowitz Social Anxiety Scale (LSAS) and completed the following self-report
      questionnaires: the Fear of Negative Evaluation questionnaire (FNE), the State
      Trait-Anxiety Inventory (STAI A-B), and the Beck Depression Inventory (BDI 13).
      RESULTS: The internal consistency is very good with Kuder-Richardson 20
      coefficient of 0,94 corresponding to coefficients found in the validity studies
      of the original version of the FNE. One factor Anova tests showed that our two
      groups of subjects differed significantly on the FNE [F (1.166)=282.26, p<0.001].
      Patients had a mean score of 25.6 with a standard deviation of 4.1 and the non
      patient control subjects had a mean score of 12.1 with a standard deviation of
      6.1. This result confirms the empirical validity of the instrument. In the
      patient sample, the FNE was significantly correlated with the LSAS total score
      (r=0.55; p<0.001). This result indicates good convergent validity. However, the
      FNE was also significantly correlated with the BDI-13 (r=0.48; p<0.001) and the
      STAI B (r=0.47; p<0.001). However because high levels of general anxiety and
      depression are common among patients with social anxiety disorder, substantial
      correlations between measures of social anxiety and measures of general anxiety
      and depression should be probably expected. A multiple regression analysis shows
      a significant association of the FNE with the LSAS (Beta=0.39, p<0.001) and the
      STAIB (Beta=0.28, p<0.01) We explored the unidimensionality of the scale by using
      a principal component analysis of tetrachoric correlation suitable for dichotomic
      items. One sole factor with an eigenvalue superior to 1 emerged. We deduce
      therefore that our results are in favour of the unidimensionality of the French
      version of the FNE. CONCLUSION: The present study shows that the French version
      of the FNE has good psychometric properties and differentiates social phobic
      patients from the non-clinical control subjects. Given the importance that models
      of social anxiety attribute to cognitive processes and the importance of
      cognitive techniques in its treatment, we consider that the French version of the
      FNE is an adequate and valid questionnaire to be used in research and therapy.

PMID- 15738854
TI  - [The mental health of new prisoners or of those monitored in French prisons with
      "services medicopsychologiques regionaux" (SMPR, Regional Medical and
      Psychological Departments)].
AB  - In France, the prevalence of psychiatric disorders has never been studied,
      despite the fact that such disorders are a major public health problem in
      prisons. Through the Services Medico-Psychologiques Regionaux (SMPR, Regional
      Medical and Psychological Departments), the psychiatric disorders of new
      prisoners, as well as the mental pathologies of the prisoners monitored by these
      services, have been analysed. All subjects arriving in prison during the month of
      June 2001, as well as all those monitored during the same period, were surveyed
      by means of a questionnaire that assessed the symptoms present on arrival in
      prison and the mental pathologies of the prisoners being monitored. Most of the
      new prisoners were male (94%). They were relatively young (31 years on average)
      and had severe problems with social insertion (12% were homeless). There were
      psychiatric symptoms in 40%, largely disorders associated with addiction or
      anxiety. The prisoners monitored by the SMPR were older and included more women,
      but the socio-economic characteristics were similar to those of the new arrivals.
      Personality disorders represented 34% of the diagnoses, a quarter of the
      prisoners being monitored suffered from mental disorders associated with the use
      of toxic substances, 12% suffered from neurotic or anxiety disorders, 8% had a
      psychotic pathology and 7% mood disorders. Psychiatric disorders are very common
      in new prisoners and the mental pathology of the subjects monitored by the SMPR
      is very specific.

PMID- 15738855
TI  - [Symptom variations in ADHD: importance of context, development and comorbidity].
AB  - Attention-deficit hyperactivity (ADHD) is a common disorder in school-aged
      children and is associated with significant impairment in social and academic
      functioning. Its recognition is based on congruent information from different
      sources, because most ADHD children and adolescents are not completely aware of
      impairments caused by inattention and/or hyperactivity/impulsivity. Fluctuations
      in symptom expression may complicate the diagnosis: during clinical examination
      or tests sessions, ADHD symptoms may be less severe than usual or completely
      absent. This review examines variations in ADHD symptoms due to environmental
      context, internal state, circadian factors, development, psychiatric comorbidity
      and discusses their clinical relevance. Generally, ADHD symptoms are pervasive
      and identified in different areas of functioning. Despite their chronicity, they
      show a relative context-dependency. An unfamiliar environment or situation may
      lessen symptoms. The same happens in dual relations or in calm settings, when the
      child receives attention and positive reinforcement from the adult. On the
      contrary, the classroom situation with its high stimulation level (noise, visual
      distractors, large class size) is likely to reveal or accentuate instability,
      impulsivity and inattention. Independently from objective symptom fluctuations,
      the impact of ADHD symptoms, and their consequences on self-esteem may also vary
      with the degree of environmental mismatch. Recent research in experimental
      psychology also draws attention to the motivational state of ADHD children:
      preference for immediate gratification and delay aversion may explain why most of
      them show satisfactory attentional capacities in certain activities (for instance
      video games or TV), while showing impairment in school work or in other effortful
      tasks. The diagnosis of the full ADHD syndrome requires significant impact on
      functioning in at least two areas. Some children with "situational" ADHD are
      impaired either in school setting or exclusively at home. Manuzza et al. report
      long-term outcome of "situational" versus "pervasive" ADHD. School-ADHD, in
      opposition to home-ADHD shows similarities with the full blown syndrome, as
      regards proportion of anti-social personality disorder, psycho-social functioning
      and academic/professional achievements. Moderate seasonal variations have also
      been identified with less ADHD symptoms in August. This result is likely to
      reflect a better fit between individual characteristics and environmental demands
      during school holidays rather than neurobiological changes, as there are no
      convincing arguments for seasonal fluctuations of serotoninergic tone in ADHD.
      Another cause for variations in ADHD symptom expression may be the co-occurrence
      of a mood disorder. Relationships between early-onset mania and ADHD are
      discussed. The appropriate definition of prepubertal mania is still in debate;
      its recognition is hindered by symptom overlap and high level of comorbid
      conditions. Chronic emotional dysregulation with irritability and frequent temper
      tantrums, sometimes viewed as characteristics of early-onset mania, might reflect
      a--possibly severe--sub-type of ADHD rather than a prodrome of bipolarity. A
      marked cyclicity of symptoms, with periodic accentuation of ADHD and mood
      symptoms, requires careful monitoring and systematic analysis of comorbid
      conditions. Clarification of the complex interrelations between ADHD and bipolar
      disorder will be obtained from long-term studies.

PMID- 15738856
TI  - [A rare and not very studied disorder: childhood-onset schizophrenia. A case
      report].
AB  - Childhood-onset schizophrenia is rare: its prevalence is about 50 times lower
      than the one observed in adulthood. It is also frequently unrecognized, notably
      because its clinical aspect varies with age. The authors report the case of a
      prepubertal girl who developed a typical clinical picture of schizophrenia
      (paranoid subtype) by age 9. CASE REPORT: The patient was 10 years old when she
      was hospitalized for a relapse of a suspected childhood-onset schizophrenia.
      Several significant mental disorders were found in her family history: her mother
      was treated for mood disorders (including dysthymia and major depression with
      postpartum onset), while her father and a aunt exhibited schizophrenic disorders.
      In addition, prenatal and perinatal events (including probable prenatal maternal
      infection and obstetric complications) were reported by her mother. Demonstrable
      impairments were already present in her premorbid development: from the age of
      3.5, she showed significant manifestations of behavioural inhibition and
      separation anxiety, severe difficulties in social adaptation, and language
      abnormalities (qualified by her general practitioner as selective mutism). At the
      age of 9, when her mother was hospitalized for a diabetes mellitus, she suddenly
      showed auditory and visual hallucinations associated with delusions. Their
      content included filiation, somatic, and persecutory themes. Grossly disorganized
      behaviour (and more particularly catatonic motor behaviours including catatonic
      rigidity and negativism and bizarre postures) was also observed. Negative
      symptoms (eg anhedonia, affective flattening, and alogia) were noted. Her IQ
      scores were 74 in the verbal subtests and 53 in the performance subtests. Because
      the diagnostic of childhood-onset schizophrenia was suspected, a neuroleptic
      treatment, haloperidol 3 mg/day, was tried. After a partial remission during a
      few months period (characterized by a decrease in delusions, anxiety and sleep
      difficulties), she showed a relapse leading to her hospitalization. At the time
      of her admission, she showed severe manifestations of separation anxiety
      including agitation, anger, crying, and insomnia, for which she received a short
      lived treatment by lorazepam. When sedation was obtained, the clinical picture
      proved similar to the one previously observed: hallucinations, delusions, grossly
      disorganized behaviour, and thought disorder were noted. As soon as the
      diagnostic of childhood-onset schizophrenia was confirmed, she was administered a
      new antipsychotic agent, amisulpride, at dose of 600 mg/day. This treatment was
      going on during several weeks with no significant clinical effect. Because the
      early onset of the disorder, the family history of schizophrenia, and the lack of
      effectiveness of the two previously administered antipsychotic agents, a
      treatment with clozapine was started at the dose of 12,5 mg/day. From the outset
      of this treatment, clinically significant reductions in hallucinations and
      disorganized behaviours were noted. Dose was then progressively increased until
      200 mg/day, resulting in significant improvement in cognitive and motor
      functioning. The patient is now in an educational institute. Her adaptation is
      considered satisfactory, in spite of regular exacerbations of delusions in
      response to stressful life events. Treatment with clozapine is going on, without
      any significant undesirable clinical effects. DISCUSSION: If an abrupt onset is
      rarely observed in prepubertal children, all the authors report that patients
      with very early onset schizophrenia show to have demonstrable impairments in
      their premorbid language as well as in their motor and social development. In
      addition, several studies suggest that more pronounced early developmental
      abnormalities are usually associated with a poor outcome in schizophrenia. The
      clinical picture also agrees with recent studies showing that in children
      paranoid subtype is as frequent as seen in adult disorders. If genetic factors
      play a significant role in the pathogenesis of schizophrenia, the notion that
      such factors may be more salient in very early onset and more severe cases is now
      usually accepted. However, a number of environmental factors, including prenatal
      maternal infections and perinatal complications, may also be implicated in the
      pathogenesis of schizophrenia, in addition to genetic factors. Because a
      significant relationship between stressful life events and exacerbations in
      positive symptoms was found in the case reported, the authors examine the role of
      such stress factors in the pathogenesis of schizophrenia and in the course of
      illness. A brief review of studies that have examined the effects of
      antipsychotic agents in children with schizophrenia underscores the paucity of
      data available to guide clinicians in this area. However, these data suggest that
      children who receive conventional neuroleptics experience significant adverse
      effects, primarily sedation and extrapyramidal symptoms. In addition, they
      suggest that new antipsychotic agents, such as clozapine, may be more effective
      than conventional neuroleptics, particularly in negative symptoms. Lastly, the
      authors emphasize the poor outcome usually reported in childhood-onset
      schizophrenia, highlighting the need of a long-term pharmacological and
      behavioural treatment. CONCLUSION: This case report, such as others, supports the
      hypo-thesis that there is a clinical continuity between early and later onset
      schizophrenia. It also suggests that very early onset schizophrenia is a more
      severe form of the disorder and may be secondary to greater familial
      vulnerability. Consequently, systematic studies of these patients may be
      particularly informative and may provide important informations for understanding
      the etiologic processes involved in the pathogenesis of schizophrenia.

PMID- 15738857
TI  - [Effect of different variables on the outcome of various cognitive-behavioral
      treatment modalities for panic disorder with agoraphobia].
AB  - The efficacy of cognitive-behavioral therapy (CBT) is clearly demonstrated in the
      treatment of panic-disorder with agoraphobia (PDA). Between 70% and 90% of people
      with PDA obtain an higher global functioning level after CBT, yet symptoms remain
      in 10 to 30% of participants after treatment termination. The goal of the present
      study is to find which variables have an effect on different CBT modalities
      (individual, group, self-help) for persons with moderate and high PDA. Eighty
      four persons were randomly assigned to one of three treatment modalities.
      Evaluations were made before treatment, immediately after and one year later.
      Results show that sex, number of years with agoraphobia and anxiety level
      significantly predict outcome at post-test for the individual modality. However,
      only the number of years with agoraphobia is a strong predictor one year later
      for this treatment modality. For the self-help modality, no predictor is
      significant neither at post-test nor one year later. For the group modality, the
      agoraphobic avoidance predicts outcome at post-test whereas symptoms severity
      predicts outcome one year later.

PMID- 15738858
TI  - [Burn-out among personnel of prisons: Karasek's job demand-control model].
AB  - The main objective of the present research was to test a path model describing
      the effects of the dimensions of the Karasek's "job strain" model on burn-out
      among a sample of personnel of prisons (n=119). This model assumes that the
      combination of high job demands along with low decision latitude at work
      precipitates psychological strain and physical illness. Job demands refer to the
      perceived demands from job and others in the workplace. Decision latitude is an
      operationalization of the concept of control and has often been defined as the
      combination of job decision-making authority and the opportunity to use and
      develop skills on the job. The findings support this model. Indeed, high level of
      workload acts positively on emotional exhaustion and depersonalization; in
      contrast, high level of job decisions latitude acts negatively on emotional
      exhaustion and positively on personnel accomplishment. Limits of this study are
      discussed.

PMID- 15738859
TI  - [Substance use, affective problems and personality traits: test of two
      association models].
AB  - The International Consortium of Psychiatric Epidemiology has confirmed the high
      comorbidity in community-drawn samples between substance use disorders and
      anxiety or depression. In the same way, associations between substance use and
      specific personality traits (such as novelty seeking, harm avoidance or
      antisocial personality) have also been extensively documented. Self-medication
      and social deviance are among the most commonly evoked explanatory models for
      these forms of comorbidity, and are based on findings that affective disorders
      and specific personality traits often precede the onset of substance use
      disorders. The self-medication model postulates that an individual chooses a
      specific substance according to its psychopharmacologic action on the given
      psychological state of the person. By contrast, the social deviance model posits
      that this form of comorbidity is due to the fact that persons consuming certain
      substances may have affective or personality characteristics that are more severe
      or more deviant than non-consumers (or than consumers of socially well-accepted
      substances). In this way, the individual does not use a particular substance to
      assuage pre-existing disorders but, due to a more deviant personality, is less
      influenced by social norms and may more easily turn to using illicit substances
      or to polyconsumption. However, a major limitation of the current scientific
      literature concerning tests of these models is that previous investigations have
      been based in overwhelming majority on clinical populations. The examination only
      of clinical samples renders difficult the identification of causal (or primary)
      risk factors for the emergence of substance use disorders from the potential
      consequences of substance use itself. The goal of the current study was therefore
      to simultaneously compare both models of association using a non clinical
      population of substance users. In addition to selecting subjects based on use
      (rather than abuse or dependence), multiple comparisons were corrected with a
      Bonferroni adjustment. METHOD: A two-phase sampling plan was used with post
      stratification on substances use. In the first stage, an initial sample of 685
      students was pre-selected based on responses to a battery of self-questionnaires,
      including information concerning recent consumption of substances (alcohol,
      cannabis, cocaine, heroin, acid, solvents, and so on), anxiety levels measured by
      the State and Trait Anxiety Inventory (STAI, Spielberger, 1983) and depression
      levels evaluated by the Center of Epidemiologic Studies Depression Scale (CES-D,
      Radloff, 1977). Based on responses to these questionnaires, 98 subjects were
      selected in the second phase to compose four groups of substance users: non
      consumers (those who did not use any substance during the last month); consumers
      of alcohol only, consumers of cannabis (with or without alcohol) and consumers of
      other illicit substances (with or without cannabis or alcohol). These subjects
      were then invited to participate in a brief laboratory-based meeting where they
      completed the Temperament and Character Inventory (TCI, Cloninger, 1992), which
      assessed different personality characteristics such as novelty seeking (NS), harm
      avoidance (HA) or antisocial personality disorder (APD). ANALYSES: The hypotheses
      concerning self-medication were tested by multiple logistic regression by
      comparing each group of substance consumption to the non-consumer group relative
      to levels of anxiety, depression and scores of novelty seeking and harm
      avoidance. The social deviance model was tested by ANOVAs using contrasts which
      allowed for a test of a linear tendency across the four groups of consumption
      relative to each of the personality traits (novelty seeking, harm avoidance and
      antisocial personality). RESULTS: Results of multiple logistic regressions showed
      no difference between non-consumers and any group of consumers with regard to
      anxiety, depression and harm avoidance. However, consumers of other illicit
      substances significantly differed from non-consumers for novelty seeking trait
      (qOR=8.4; p<0.05). Results of the ANOVA also showed no differences between the
      four groups with regard to scores of harm avoidance and level of antisocial
      personality but again a comparison of novelty seeking scores was significant,
      F(94)=6.46, p<0.05. Moreover, the contrast method demonstrated that novelty
      seeking scores increased linearly and significantly (p<0.001) from the group of
      non-consumers to the group of the consumers of the most deviant substances.
      CONCLUSION: The results obtained in this non-clinical sample are in favor of
      social deviance model which posits that the personality trait of novelty seeking
      is associated to the consumption of the most illicit and deviant substances (such
      as heroin or cocaine). On the other hand, no support was found for the hypothesis
      of self-medication which assumes that specific substances should be particularly
      associated with specific psychological characteristics or vulnerabilities.

PMID- 15738860
TI  - [Awareness of deficits and anosognosia in Alzheimer's disease].
AB  - This article reviews studies concerning unawareness of deficits in Alzheimer's
      disease. Unawareness of the deficits associated with dementia has frequently been
      reported in clinical descriptions of the later stages of the disease. Consistent
      with the literature, we shall use the expressions impaired awareness, unawareness
      of deficits, anosognosia, and lack of insight interchangeably. Anosognosia can be
      defined as an impaired ability to recognize the presence or appreciate the
      severity of deficits in sensory, perceptual, motor, affective, or cognitive
      functioning. Unawareness has been operationally defined in a variety of ways.
      Unawareness can be measured as the discrepancy between the patient's self-report
      and the report of a natural caregiver or the clinical rating of a health care
      professional. The reports generally concern with several domains, most often
      memory domain. Discrepancy between subjective ratings and neuropsychological
      performance during clinical assessment has also been used to measure anosognosia.
      Advantages, limits and equivalence of these different methods are discussed. The
      impact of family burden has to be considered as a systematic methodological bias
      if the natural caregiver is implicated in the assessment. The psychometric
      properties of the clinical assessment have also to be discussed. The
      psychological nature of the discrepancy between patient's self-report and
      cognitive performances has to be analyzed and the necessity of ecological
      protocols, longitudinal assessment is discussed. The major results concerning
      prevalence, nature of anosognosia and the associated disorders are analyzed. In
      particular, the notion of heterogeneity of anosognosia and the correlates with
      depression, severity of dementia and executive dysfunction are developed.
      Prevalence is largely function of methodological choices and conceptual
      definition of anosognosia. Three major researches are compared and the contrast
      between their results (prevalence from 23% to 75% in AD) is analyzed.
      Particularly, the hypotheses about anosognosia play a great role in the findings.
      At first time of research, anosognosia was considered as a general symptom and
      so, studies were centered on the unawareness related to only one cognitive
      function. But the 90's findings suggest that patients with AD have impaired
      awareness for some types of deficits (affective or cognitive functions) but can
      more accurately appraise other deficits. Currently anosognosia cannot be
      considered as a unitary entity. It may be that patients with AD are unaware of
      some types of deficits, but are aware of others, and that nature and intensity of
      their anosognosia may change during the course of the dementia. It has been
      proposed that depression is more common when disease is mild and awareness of
      deficits is retained, and that depression becomes less common when disease
      increases and awareness declines. Depression is conceived as a psychological
      reaction. However, the correlations between anosognosia level and depression
      scores reveal either weak relationships or no relationships. Alternative
      hypothesis is that anosognosia is related to overall dementia severity and to
      memory impairment. However, correlations of unawareness of deficits, i.e. the
      difference between self-report and relative's -rating, with a measure of dementia
      and with patient's performance on objective memory tasks did not reveal strong,
      consistent relationships between degree of anosognosia and severity of dementia
      or of memory impairment. On the other hand, the best neuropsychological
      predictors of impaired insight are Trail Making Test or Wisconsin Card Sorting
      Test, i.e. tests that have been shown to be sensitive to a frontal lobe
      dysfunction. SPECT measures of regional cerebral blood flow have been used in the
      study of anosognosia. The main findings are that unawareness in AD is associated
      with hypoperfusion of the right dorsolateral frontal lobe. Anosognosia may result
      from the disruption of broader cognitive process that is subsumed by the frontal
      lobes. The mechanisms of unawareness are not well known and studies are
      essentially descriptive works and try to give information about pre-valence or
      clinical associated disorders of anosognosia. Several authors have proposed that
      unawareness is part of a defensive mechanism that would protect demented patients
      from depressive feelings. Other authors have proposed that anosognosia may result
      from dysfunction in specific brain areas. It is suggested that anosognosia in AD
      may result from greater impairment of a central executive system, which is a
      metacognitive structure that is involved in planning, cognitive resource
      allocation, and set shifting. The main problem with those both major hypotheses
      is their incapacity to explain the heterogeneous impairment of awareness. Other
      authors speculate that the impaired insight of Alzheimer's disease has several
      components, psychological and neuropsychological. This view doesn't seem
      convincing and new components have to be taken in account in order to propose a
      theoretical framework about anosognosia in AD. Environmental and dispositional
      components and an interactional view could be interesting. Those possible
      directions for future research and solutions concerning methodological and
      conceptual problems are outlined. In particular, a neuro-psycho-social view of
      unawareness is introduced.

PMID- 15738861
TI  - [Treatment of clozapine-induced granulocytopenia with lithium (two
      observations)].
AB  - Despite the availability of new treatments, the antipsychotic effectiveness of
      clozapine has not been matched yet. Unfortunately, its regulation is limited by
      the side effects. The most detrimental is the hematologic toxicity (neutropenia
      and agranulocytosis) which requires a regular biological monitoring. Treatment
      with clozapine must be stopped in those cases of secondary granulocytopenia for
      about 3% of the patients. The current psychiatric drug lithium carbonate has an
      opposite effect: it can induce leukocytosis. Thus, lithium carbonate is
      administered in leukopenia, as well as in many hematologic and immunological
      diseases. However, few teams have used lithium in order to alleviate clozapine
      induced granulocytopenia. We report here 2 patients who developed severe
      neutropenia (neutrophil count<1.5 yen 10 (9)/L) and for whom the use of lithium
      enabled us to continue the treatment by clozapine. The first patient had a
      granulocyte rate constitutionally low which rapidly decreased with clozapine.
      Thanks to the administration of lithium, he recovered quickly a normal blood cell
      count, which in fact was much higher than his normal rate. According to our
      research, it's the first time that lithium is reported to be so efficacious in a
      patient with such a low rate of granulocytes before treatment. It may be that
      clozapine is not used for those kinds of patients. The second patient developed
      granulocytopenia after one year of treatment with clozapine. The use of lithium
      increased so much the number of granulocytes that we continued the treatment with
      clozapine alone. After 4 months, there is no reappearance of granulocytopenia. We
      must take into account the partial and contradictory reports in the literature.
      However, if this result is confirmed, it could be of a high interest to extend
      the prescription of clozapine, the most effective current antipsychotic drug.

PMID- 15738863
TI  - [Basocellular carcinoma that everyone's talking about].

PMID- 15738862
TI  - [Efficacy of atypical antipsychotics in depressive syndromes].
AB  - Depression is a frequent symptom in psychiatry, either isolated (major
      depression) or entangled with other psychiatric symptoms (psychotic depression,
      depression of bipolar disorders). Many antidepressant drugs are available with
      different pharmacological profiles from different classes: tricyclic
      antidepressants, monoamine oxydase inhibitors, selective serotonin reuptake
      inhibitors (SSRI). However, there are some limitations with these drugs because
      there is a long delay before relief for symptoms, some patients with major
      depression are resistant to treatment, there is a risk to induce manic symptoms
      in patients with bipolar disorders and these drugs have no effect on the
      psychotic symptoms frequently associated to major depression. The leading
      hypothesis for the search of more efficient new antidepressants has been the
      amine deficit hypothesis: noradrenaline and/or serotonin deficit and more
      recently dopamine deficit. Moreover, a dopamine deficit has been also
      hypothesized as the central mechanism explaining the negative symptoms of
      schizophrenia. These symptoms are the consequence of a deficit of normal
      behaviours and include affective flattening, alogia, apathy, avolition and social
      withdrawal. There is thus a great overlap between symptoms of depression and
      negative symptoms of schizophrenia. Atypical antipsychotics, in contrast with
      conventional neuroleptics, have been shown to decrease negative symptoms, most
      probably through the release of dopamine in prefrontal cortex, thus improving
      psychomotor activity, motivation, pleasure, appetite, etc. The dopamine deficit
      in cortical prefrontal areas was thus an unifying hypothesis to explain both some
      symptoms of depression and negative symptoms of schizophrenia. Studies in animal
      confirm this view and show that the association of an atypical antipsychotic drug
      and an SSRI (olanzapine plus fluoxetine) increases synergistically the release of
      dopamine in prefrontal areas. Moreover, most of the atypical antipsychotics have
      a large action spectrum, beyond the only dopamine receptors: their effects on the
      serotonin receptors--particularly the 5-HT2A and 5-HT2C receptors--suggest that
      their association to SSRI could be a promising treatment for depression. Indeed,
      SSRI act mainly by increasing the serotonin level in the synapse, thus leading to
      a non specific activation of all pre- and post-synaptic serotonin receptors.
      Among them, 5-HT2A/2C receptors have been involved in some of the unwanted
      effects of SSRI: agitation, anxiety, insomnia, sexual disorders, etc. The
      inhibition of these receptors could be thus beneficial for patients treated with
      SSRI. Amisulpride is an unique atypical antipsychotic that selectively blocks
      dopamine receptors presynaptically in the frontal cortex, possibly enhancing
      dopaminergic transmission. The antidepressant effect of amisulpride was shown in
      dysthymia in many clinical studies versus placebo, tricyclic antidepressants,
      SSRI or others. However, a shorter delay for symptom relief was not demonstrated
      for amisulpride as compared to comparative antidepressants. Other atypical
      antipsychotics (clozapine, olanzapine), which act on a large variety of
      receptors, have shown antidepressant effects--mainly in association with SSRI--in
      different psychiatric diseases: treatment-resistant major depression, major
      depression with psychotic symptoms and depression of bipolar disorders, with no
      increase of manic symptoms in this latter case. Moreover, the delay for symptom
      relief was greatly shortened. More comparative double-blind studies are required
      to confirm and to precise the antidepressant effects of atypical antipsychotics.
      Nevertheless, these studies suggest that atypical anti-psychotics could be of
      great value in depressive conditions reputed for their resistance to treatment
      with usual antidepressants. Particularly, new strategies emerge that combine
      atypical antipsychotics and antidepressants for greater efficacy and more rapid
      relief of depression symptoms.

PMID- 15738865
TI  - [Immunohistochemical characterisation of the main histologic subtypes of
      epithelial renal tumours on tissue-microarrays. Study of 310 cases].
AB  - OBJECTIVE: Diagnosis of renal epithelial tumours of adult is often easily made.
      Nevertheless, it can be difficult to distinguish clear cell carcinoma (CCC) and
      chromophobe carcinoma (CCHRO), or the eosinophilic variants of CCC and CCHRO with
      papillary carcinoma (CTP) and oncocytoma (ONCO). The objective is to study and
      validate immunohistochemical phenotypes of these tumours and to evaluate if they
      are helpful and to define a diagnostic strategy. MATERIALS AND METHODS: 310
      tumours (75 CCC, 89 CTP, 50 CCHRO and 96 ONCO) were collected and put on 4 tissue
      arrays blocks. Immunohistochemical stainings were performed with some usual
      antibodies: pancytokeratin AE1-AE3, EMA, vimentin, CD10, CK7, CK20 and RCC (Renal
      Cell Carcinoma). RESULTS: Pancytokeratin AE1-AE3 is expressed mainly in CTP
      (82.5%). The cytoplasmic staining of EMA is seen in almost all CCHRO (98%) and
      more than half of CTP (57%). Vimentin is rather specific of CCC (54.5%) and CTP
      (85%) whereas it is negative in ONCO and CCHRO. CD10 is expressed in the majority
      of CCC (86.5%) and in some of CTP and CCHRO 65 and 39% respectively. CK7 is
      rather specific of CTP and CCHRO with 79 and 81.5% of positivity rate. Based on
      statistical analysis, we have built a diagnostical tree allowing to distinguish
      79% of tumours using only three antibodies: CK7, vimentin and CD10. CONCLUSION:
      CCC are CK7-/Vim-/CD10+ or CK7-/Vim+; CTP are CK7+/Vim+; CCHRO are CK7+/Vim-; and
      ONCO CK7-/Vim-/CD10-. In the oncocytoma/chromophobe group, ONCO are more often
      CK7-/EMA- and CCHRO CK7+/EMA+.

PMID- 15738866
TI  - [Synaptophysin expression abnormalities in Hirschsprung's disease].
AB  - Hirschsprung's disease is defined by the congenital absence of ganglion cells in
      enteric plexuses. Immunostaining of synaptophysin after formalin fixation may be
      used to identify hyperplasia of nerve fibers and rarefaction of neuromuscular
      junctions in Hirschsprung's disease. The aim of the study was to evaluate semi
      quantitatively the expression of synaptophysin in Hirschsprung's disease, in
      correlation with morphologic features. This retrospective study included 3
      controls, 42 surgical rectal biopsies performed for suspicion of Hirschsprung's
      disease in children presenting with lower digestive occlusion or severe chronic
      constipation, including 18 Hirschsprung's disease, and 23 surgical specimens of
      Hirschsprung's disease. In the absence of Hirschsprung's disease, synaptophysin
      positive fibers were numerous but thin in the muscularis mucosae, thin and scarce
      in the mucosa and submucosa. Neuromuscular junctions were thin and numerous in
      the muscularis propria. In Hirschsprung's disease, synaptophysin-positive fibers
      were coarse, and increased in number on each side of the muscularis mucosae.
      Plexuses were enlarged, weakly stained, and associated in the connective tissue
      of the muscularis propria with coarse and intensely stained fibers. In
      conclusion, staining for synaptophysin could be useful to demonstrate
      abnormalities of enteric innervation in rectal biopsies performed for suspected
      Hirschsprung's disease in the absence of acetylcholinesterase staining on frozen
      sections, in transmural biopsies performed for guiding surgery in Hirschsprung's
      disease, and in cases of extensive Hirschsprung's disease.

PMID- 15738867
TI  - [The pathologist and EGFR in 2004: I like you, nor do it].
AB  - Epithelial growth factor receptor (EGFR) appears as a key element in
      carcinogenesis. It displays high levels of expression in some tumor types. Its
      activation induces cell proliferation, angiogenesis, cell mobility and inhibition
      of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules
      tyrosine kinase inhibitors have been developed. For EGFR, the diversity of the
      activation means (amplification, mutation, enhanced transcription, ligands...)
      leads to technical caveats. Immunohistochemistry appears to be the most
      appropriate test for clinical use, but standardized assays and scoring systems
      are mandatory. Pathologists are involved in the selection of patients for a
      monoclonal antibody based targeted treatment, Erbitux, and numerous
      standardization efforts are provided. No consensus has been reached, to date, for
      a scoring system. Whether the EGFR status has to be tested for the selection of
      patients is a non answered question. The selection of the "right patient for the
      right treatment" might be through the evaluation of other putative markers
      involved in resistance. EGFR testing may be required before targeted treatment.
      An exciting endpoint might be the functional and dynamic evaluation of EGFR and
      downstream proteins, for patients, before and during treatment. The exact role of
      the pathologist still have to be accurately determined.

PMID- 15738868
TI  - [Solitary cutaneous infantile myofibromatosis].
AB  - Infantile myofibromatosis is the most frequent fibromatosis in childhood. It is a
      benign proliferation of fibroblasts and myofibroblasts. This case report concerns
      a newborn who presented at birth with a purple cutaneous nodule on the scalp.
      Surgical excision was performed at the age of 16 months. Infantile
      myofibromatosis was diagnosed on histology. Infantile Myofibromatosis (IMF) was
      first described by Enzinger in 1981. Three types can exist. Solitary MFI, the
      most frequent, is a solitary lesion, cutaneous/subcutaneous, osseous or involving
      soft tissues. Multicentric disease is characterized by multiple locations and
      generalized form by visceral involvement. Morphological features are identical in
      all types. The histological diagnosis relies on the identification of two
      separate components, a fascicular myofibroblastic pattern at the periphery with a
      hemangiopericytoma like pattern in the centre. Both components are positive for
      alpha-smooth muscle actin. Atypia, or mitotic activity, are not observed usually
      but features of intravascular growth can be seen in the centre of the lesion.
      Infantile MF carries a good prognosis when solitary but death frequently occurs
      in generalized MF with visceral involvement.

PMID- 15738869
TI  - [Secretory breast carcinoma in a man. A case report with rapid evolution
      unfavorable].
AB  - Secretory carcinoma or juvenile carcinoma of the breast is a very rare tumor of
      male adults. Generally, it has a good prognosis after locoregional treatment. The
      authors report an observation of a secretory carcinoma occurring in a 20 year old
      man. The lesion presented as a voluminous tumor 12 cm in diameter with 3 positive
      lymph nodes; it was treated by mastectomy and axillary dissection. Tumor
      developed in a few months, with visceral metastasis and fatal issue. The
      cytological, histological and immuno-histochemical features necessary to the
      diagnosis are described. The rapid development of this case of secretory
      carcinoma is unusual. This leads the authors to propose the use of an additional
      treatment for adult secretory breast carcinoma with more than 3 positive lymph
      nodes.

PMID- 15738870
TI  - [A-leukemic caecal myeloid sarcoma: a difficult diagnosis].
AB  - Myeloid sarcoma is a malignant neoplasia composed of abnormal myeloid or
      monocytic cells, often localized in bones, but also rarely in extra-medullary
      sites such as lymph nodes, skin and soft tissue. We report a case of caecal
      myeloid sarcoma, diagnosed in a 60 year old woman who complained from abdominal
      pain and weight loss, in absence of any medullary disorder. Initially
      misdiagnosed as a B lymphoma because of a weak positivity for CD79a, the
      diagnosis of primitive caecal myeloid sarcoma was eventually established after
      further investigations showing a positivity for lysozyme and myeloperoxidase.
      This report of such a rare clinical and pathological presentation of a myeloid
      sarcoma underlines a difficult differential diagnosis for which adequate
      immunohistochemistry, including lysozyme and myeloperoxydase is mandatory.

PMID- 15738871
TI  - [Clear cell dermatofibroma: a case report with cytogenetic study].
AB  - We report an observation concerning a 48-year-old male who presented with a 5 cm
      tumour on his left leg, first noticed 18 months ago. The remainder of clinical
      examination was normal. Histological assessment revealed a tumoral infiltration
      of entire dermis and superficial hypodermis. This tumour consisted of
      monomorphous, ovoid or spindle cells, with clear cytoplasm and PAS+ granulations.
      There was strong immunoreactivity by tumoral cells only for vimentin.
      Ultrastructural studies revealed fibrohistiocytic-like tumoral cells, without
      epithelial, muscular, vascular or melanocytic differentiation. These results were
      consistent with the diagnosis of clear cell dermatofibroma. Cytogenetic
      evaluation and FISH analysis showed a deletion of p12. Clear cell dermatofibroma
      is a rare and recent variant of dermatofibroma, with a difficult histological
      evaluation and which must be differentiated from clear-cell sarcoma. This
      observation is the first case-report of this entity, to our knowledge, showing a
      cytogenetic abnormality.

PMID- 15738872
TI  - [Extra-nodal Rosai-Dorfman disease: a case report with thyroid involvement].
AB  - Extra nodal involvement by Rosai-Dorfman disease (RDD) is not rare but remains
      poorly described clinically and microscopically. We report a case of RDD
      involving the thyroid and revealed by a 15 mm cold nodule developed on an ancient
      goiter. The patient was a 53 year old North African woman. She also presented an
      involvement of cervical lymph nodes, respiratory tract and right kidney.
      Microscopic analysis of thyroid revealed a diffuse and dense infiltrate of large
      pale histiocytes with few features of lymphophagocytosis. To the best of our
      knowledge, this is the fifth case reported in the literature. In previous
      reported cases, thyroid RDD was associated to constant lymph node involvement
      (massive lymphadenopathy in 3 cases and occult in one case) and no other extra
      nodal localization except the respiratory tract in one case. The characteristic
      features of lymphophagocytosis must be searched with great care.

PMID- 15738873
TI  - [Image in pathology].

PMID- 15738874
TI  - [An unusual axillary lymph node].

PMID- 15738875
TI  - [An unusual dermal congenital entity].

PMID- 15738876
TI  - [An uncommon tumor of the kidney].

PMID- 15738877
TI  - [A tumor of the mandible].

PMID- 15738878
TI  - [Recommendations for the diagnostic and therapeutic management of basal cell
      carcinoma in adults].

PMID- 15738879
TI  - [HSP86, germ cells and yolk sac tumor].

PMID- 15738881
TI  - [Neural transplantation for the treatment of Parkinson's disease. Update and
      future].
AB  - Cell transplantation to replace lost neurons is a recent approach to the
      treatment of progressive neurodegenerative diseases. Replacement of dopaminergic
      neurons in patients with Parkinson's disease (PD) was the first transplantation
      therapy to be tested in the clinical setting. In PD, cell replacement strategy
      has been based on the idea that neural graft-induced restoration of dopamine
      neurotransmission in the striatum could lead to substantial and long-lasting
      functional recovery. Since transplantation of embryonic dopaminergic cells was
      first reported in the early 1990s, several open-label clinical trials have
      confirmed the benefits of transplantation. But, the validity of these studies has
      been uncertain because of small patient numbers, variable inclusion criteria, and
      the absence of control groups. Two controlled trials have been recently designed
      and performed. Their designs incorporated a "sham-operated" versus a transplant
      group. The conclusions drawn by both teams are that fetal mesencephalic allograft
      can not, at present, be recommended as a treatment for severe PD. However,
      several lessons can be learnt and the efficacy can be improved employing more
      neurons and better targets, and/or neurotrophic factors.

PMID- 15738882
TI  - [The Bryan cervical disc prosthesis. Preliminary clinical experience with nine
      implants].
AB  - PURPOSE: After an anterior cervical discectomy, immobility at the fused level may
      increase stress on adjacent disc spaces and causes disc degeneration in 92% of
      the cases with clinical manifestations in 25.6% of the patients within 10 years.
      The cervical disk prosthesis may help to prevent this problem. The Bryan
      prosthesis (Medtronic Sofamor Danek) is currently available in France after a
      European pilot study. METHODS: Since January 2002, 8 patients (9 implants) (mean
      age: 35 years) were operated on with a prosthesis implantation for disc
      degeneration after an adjacent previous interbody fusion in 2 patients and for
      disc herniation or spondylosis in 6 patients. The prosthesis were implanted at
      the C4-C5 level (one patient), C5-C6 (four patients), and C6-C7 (four patients).
      Post-operative radiological evaluations with dynamic X-rays and clinical status
      (Odom questionnaire) were analyzed. RESULTS: Surgical procedures, which were
      longer than the classical technique, were uneventful. Radicular pain resolved
      after surgery with excellent results with the Odom's score. With a mean follow-up
      of 12 months, the prosthesis mobility was 8.9 degrees . But one fusion of an
      implant was encountered 6 months after implantation. CONCLUSIONS: The general
      follow-up for the Bryan(R) cervical disc prosthesis implantation is still too
      short (2 years) for a definitive evaluation. If clinical results on pain are as
      good as expected, long-term mobility of the prosthesis has to be checked, as it
      is the main advantage over classical anterior cervical discectomy with fusion.
      Patient selection has to be considered.

PMID- 15738883
TI  - [Interest of porous biomaterials in spinal surgery].
AB  - PURPOSE OF THE STUDY: The aim of this work was to study the behavior of porous
      alumina ceramic cages in spinal cervical surgery, with or without plate fixation
      as needed. MATERIAL AND METHODS: The population included 61 patients who
      underwent spinal surgery between May 1999 and October 2003. There were 48 women
      and 13 men, mean age 49 years at surgery. 74 implants were used, among them 71
      were interbody cages. Ten patients were operated at two levels; C5-C6 and C6-C7
      were most frequently instrumented. Patients were reviewed at 1 month, 3 months
      and 6 months, and, whenever possible more after. Clinical and radiological data
      were available for all patients. RESULTS: Mean follow-up was 7.2 months.
      Postoperative clinical data included assessment of neck and arm pain, using a
      visual analogic scale and fusion status determined by the presence of trabecular
      bridging bone and the disappearance of lucent lines around the implant on plain
      anteroposterior and lateral cervical radiographs. Two patients required another
      intervention, allowing intra-operative assessment of the quality of fusion.
      Clinical results were in agreement with the usual outcome reported in the
      literature with 54% of patients free of postoperative neck or arm pain and
      restriction of function mild or absent in 88%. Bone healing was achieved at 6
      months on the average in 58 cases and in all patients at 12 months, including the
      two patients who required revision. DISCUSSION: The porous alumine cage is a
      reliable biocompatible and mechanically stable element helpful for achieving bone
      healing. Integration into bone tissue was radiographically satisfactory. This
      kind of implant appears to be an attractive alternative in spinal cervical
      surgery, avoiding donor graft site complications.

PMID- 15738884
TI  - [Central neurocytoma. Four patients].
AB  - We report four cases of central neurocytoma we operated on at our institution,
      between 1994 and 2002. This uncommon lesion occurred in young patients, was
      located in the lateral ventricules and was revealed by signs of intracranial
      hypertension. The tumor was totally removed in three cases and subtotally in one.
      Immunohistochemistry provided useful information to distinguish neurocytoma from
      other nervous system tumors. Prognosis was excellent in two patients. One patient
      developed tumor recurrence seven years after surgery, without any progression on
      further follow up evaluation. In the last patient, the tumor showed a more
      aggressive progression requiring the adjunction of radiosurgery.

PMID- 15738885
TI  - Late spinal dislocation after treatment of spinal arteriovenous malformation. A
      case of Charcot spinal arthropathy.
AB  - Neuropathic arthropathy of the spine is a destructive condition of the spine
      which is secondary to a loss of the protective proprioceptive reflexes. In the
      majority of cases, it occurs in patients who have suffered from traumatic
      medullary lesions and is responsible for destruction of the vertebral bodies and
      considerable spinal deformity. We report a case of neurogenic lumbar arthropathy
      in a patient with a spinal arteriovenous malformation. This vascular lesion
      caused considerable disturbances of proprioception. The course was favorable with
      regard to the deformity after correction and fusion by posterior approach.

PMID- 15738886
TI  - [Atlantoaxial synovial cyst. A case report].
AB  - The case of a 62-year-old patient with an atlanto-axial synovial cyst is
      presented. The narrowing of the spinal canal was associated with anterior
      medullar compression and neurological deficit. A transoral approach with odontoid
      resection was performed. The diagnostic of synovial cyst was histologically
      confirmed. Secondary atlanto-axial instability required posterior fixation
      completed by C1-C2 transarticular screw fixation. The follow-up showed an
      improvement of the neurological deficit. Similar cases reported in the literature
      are reviewed and discussed.

PMID- 15738887
TI  - [Vertical fracture of the odontoid process. A case report].
AB  - Odontoid process fractures are commonly classified as types I through III
      according to the Anderson & D'Alonzo scheme. A fourth type of fracture not
      included in this classification has been described as "vertical odontoid
      fracture". These fractures are located in the vertical plan of the dens. We
      describe a new case of an oblique coronally oriented fracture through the
      odontoid process with extension to the body of C2. Our patient is a 22-year-old
      lady who sustained a road traffic accident with head, facial and cervical trauma.
      Computed tomography with 2D and 3D reconstruction characterized the fracture. We
      suppose that the mechanism of injury was an axial load associated with dorsal to
      ventral force. The patient was placed on a halo-vest for 12 weeks with good
      healing and no evidence of instability on flexion-extension studies 6 months
      later. This case demonstrates that the odontoid and C2 vertebral body fractures
      belong to the same spectrum and are determined by the patient's anatomy and the
      mechanism of the injury.

PMID- 15738888
TI  - [Brindley technique with intradural deafferentation and extradural implantation
      by a single sacral laminectomy].
AB  - AIM: We propose an improved technique for implanting a sacral root stimulator
      associated with dorsal sacral rhizotomy ("Brindley's technique") in a single
      intra-sacral approach. METHOD: This novel technique only requires a single sacral
      laminectomy, consisting in a sacral deafferentation at the level of the dural cul
      de-sac, facilitated by the anatomical identification of the sacral roots at this
      level. RESULTS: Four patients underwent surgery using this technique since
      October 2002, resulting in a very satisfactory micturition status. DISCUSSION:
      The aim of this technique, which is as rapid as the conventional intra-dural
      technique, is to obtain complete deafferentation and to induce non traumatic
      transdural motor stimulation at the same level. In this way, surgical goals can
      be reached more readily with greater safety than with other techniques.

PMID- 15738889
TI  - [How can the prognosis of gastric cancer be improved in France?].

PMID- 15738890
TI  - Postoperative chemoradiotherapy after surgical resection of gastric
      adenocarcinoma: can LV5FU2 reduce the toxic effects of the MacDonald regimen? A
      report on 23 patients.
AB  - AIM OF THE STUDY: A North American phase III trial has recently shown that
      postoperative chemoradiotherapy using the FUFOL Mayo Clinic regimen improves
      overall survival and relapse-free survival after surgical resection of gastric
      cancer. However, severe grade 3-4, hematologic and gastrointestinal toxicities
      were frequent. The aim of this retrospective and multicentric study was to
      determine the tolerance of a postoperative chemoradiotherapy regimen using LV5FU2
      instead of the Mayo Clinic regimen. PATIENTS AND METHODS: Twenty-three patients
      with resected adenocarcinoma of the stomach or gastroesophageal junction at high
      risk of recurrence were treated with LV5FU2 chemotherapy and radiotherapy (45 Gy
      in 25 fractions and 5 weeks) delivered to the tumor bed and regional nodes.
      Nineteen patients were treated with two to four cycles before radiotherapy, then
      three cycles during radiotherapy, and finally four cycles after radiotherapy;
      four patients were only given three cycles during radiotherapy. RESULTS: Of the
      23 patients assigned to this protocol, 20 completed treatment (87%). There was
      only one interruption of treatment because of hematologic or gastrointestinal
      toxicity. Tolerance of LV5FU2 regimen associated with radiotherapy was excellent:
      one grade 3 or 4 gastrointestinal toxicity (4.3%), no toxic death, and only one
      grade 3 neutropenia (4.3%) were reported. CONCLUSION: Radiotherapy combined with
      LV5FU2 appears to be better tolerated than the Mayo Clinic regimen used in the
      North American study. These results have to be considered when elaborating future
      postoperative chemoradiotherapy trials for gastric cancer.

PMID- 15738892
TI  - Epidemiology and long term survival of gastric carcinoma in the French district
      of Finistere between 1984 and 1995.
AB  - OBJECTIVES: The aims of this study were to evaluate trends in incidence, clinical
      characteristics, treatment regimen and prognosis of gastric carcinoma in the area
      of Finistere (France) during a 12-year period. METHODS: Between 1984 and 1995,
      the Finistere Registry of GastroIntestinal Tract Tumors listed 2 139 patients
      with gastric carcinoma in a population of 838 627 inhabitants. Curative resection
      and operative mortality were analyzed by logistic regression. Prognostic factors
      were determined using the Kaplan-Meier method and the Cox model. RESULTS: When
      comparing the second period (1990-1995) to the first period (1984-1989) we
      observed: a) a decrease of standardized incidence (13.2 vs. 15.6/100 000
      inhabitants/year in males and 5.4 vs. 7.0/100 000 inhabitants/year in females);
      b) a significant increase of linitis plastica (21.4% vs. 10.9%) and infiltrative
      tumors (53.1 vs. 31.2%) (P<0.0001); c) no variation in tumor stage at diagnosis;
      d) a significant increase in curative resection (65.7% vs. 45.0%; P<0.0001); e)
      no variation in operative mortality; f) the absence of improvement of survival
      rate; the latter was 29% at 2 years, 19% at 5 years and 11% at 10 years during
      the second period. Multivariate analysis showed that the main prognostic factors
      of gastric carcinoma were age, tumor stage and the type of surgical procedure.
      CONCLUSION: This study showed a decrease in the incidence of gastric carcinoma
      over time and an increase of linitis plasticia and infiltrative forms. Despite
      improvement in management of patients, the global prognosis of gastric carcinoma
      did not improve significantly over a 12-year period of observation.

PMID- 15738891
TI  - A prospective national study on colonoscopy and sigmoidoscopy in 2000 in France.
AB  - AIM: The aim of this study was to evaluate the practice of colonoscopy and
      sigmoidoscopy in France in 2000. METHODS: A prospective study was conducted in
      November 2000 using questionnaires sent to all gastroenterologists practicing in
      France (N=2858) who were asked to reply to items concerning colonoscopies and
      sigmoidoscopies performed on two workdays chosen in advance. The response rate
      was 32.8%. Data were extrapolated to establish estimates for the entire year.
      RESULTS: An estimated 894000 colonoscopies and 115320 sigmoidoscopies were
      performed in 2000. Single-use material was used in 22.1% of the procedures.
      Indications for endoscopy were mainly hematochezia (21.6%), gastrointestinal
      symptoms (35%) and surveillance of patients with a history of previous
      polypectomy (15%). Colorectal cancer screening was the indication for 20% of
      colonoscopies. Abnormal findings were reported for 54.8% of the endoscopies
      (polyps for 287218 procedures and cancer for 32799). Failure was noted in 4.9% of
      colonoscopies. The complication rate was 0.48%. Most polyps were adenomas (64.4%)
      or hyperplasic polyps (28.1%). The overall estimated number of colonoscopies with
      polypectomy was 224133. CONCLUSION: In 2000 there was an increased rate of
      colonoscopy for colorectal cancer screening (20%) but an overall decrease (2.5%)
      in the total number of colonoscopies compared to 1999. Abnormal findings were
      disclosed by 54.8% of the procedures. Extrapolation from these data indicates
      that colonoscopic screening enabled the diagnosis of 32799 colorectal cancers.

PMID- 15738893
TI  - [Mitochondrial DNA mutations and colorectal cancer].

PMID- 15738894
TI  - [Recommendations for clinical practice: 2004 Standards, Options and
      Recommendations for management of patients with adenocarcinomas of the stomach
      (excluding cardial and other histological forms of cancer) Federation nationale
      des centres de lutte contre le cancer].

PMID- 15738895
TI  - [Should the disposal of material after home injections be a concern?].

PMID- 15738896
TI  - [Diagnosis of gallbladder diseases by endoscopic ultrasound].

PMID- 15738897
TI  - Disposal of injection material used for the treatment of hepatitis C: comparison
      with insulin-dependent diabetes and thromboembolism.
AB  - AIM: The survey conducted in the Provence-Alpes-Cote d'Azur region in France in
      1999 showed that 38% of patients infected with the hepatitis C virus (HCV)
      receiving interferon injections in their home were aware of the recommendations
      concerning the disposal of injection material and that 41% of the needles were
      discarded with household waste after use. The purpose of our study conducted in
      the Centre region of France was to ascertain how injection material used by HCV
      positive patients for interferon treatment are disposed of in comparison with
      material used by patients injecting insulin for insulin-dependent diabetes
      mellitus (IDDM) or low-molecular-weight heparin (LMWH) for thromboembolism.
      MATERIAL AND METHODS: A questionnaire to be completed by patients was proposed to
      HCV-positive patients attending hepatogastroenterology clinics in the Centre
      region hepatitis C network for therapeutic follow-up (N=113 patients) between
      October 2001-January 2002. The same questionnaire was proposed to patients
      attending follow-up consultations for insulin-dependent diabetes mellitus (N=85
      patients) or thromboembolism (N=23 patients) between March-June 2002. RESULTS:
      Significantly more patients stated they were aware of recommendations for
      disposal of injection material in the HCV group (89%) than in the IDDM (67%) or
      LMWH (26%) groups (P<0.01). Injection material was discarded with household waste
      less often by patients in the HCV group (6%) than in the IDDM (32%) or LMWH (29%)
      groups (P<0.001) and more often collected in a safety box prior to incineration
      (73% in the HCV group versus 63% and 14% in the IDDM and LMWH groups
      respectively). The safety box was discarded with household garbage more often by
      patients in the IDDM (54%) or LMWH (50%) groups than in the HCV group (0%)
      (P<0.001). Equivalent proportions of the patients said they recapped the needle
      after use (HCV 83%; IDDM 93%; LMWH 84%). DISCUSSION: Information concerning use
      of safety boxes for disposal of injection material should be provided to patients
      in order to comply with regulatory recommendations on proper disposal of used
      injection material. Moreover, the habit of recapping needles (89% of all patients
      in this study) is still widespread.

PMID- 15738898
TI  - Tonsillar metastasis revealing signet-ring cell carcinoma of the rectum.
AB  - A 45-year-old man presented with a tonsillar tumor and rectal syndrome. Histology
      specimens revealed signet-cell adenocarcinoma of both the tonsils and rectum. The
      clinical course was rapidly degenerated with multiple metastases in the skin and
      bones. Tonsil metastasis is rare and generally develops from primary gastric or
      colorectal cancer, predominantly poorly-differentiated or signet-ring cell
      adenocarcinomas.

PMID- 15738899
TI  - [Eosinophilic esophagitis: 3 case reports].
AB  - Eosinophilic esophagitis is a rare entity, characterized by eosinophilic
      infiltration of the oesophagal mucosae, with no gastroesophageal reflux. Food
      allergies are often involved. We report 3 paediatric cases of eosinophilic
      esophagitis, revealed by dysphagia, with or without stricture. Eosinophilic
      esophagitis is a rare disease, but its frequency is probably underestimated.
      Symptoms are sometimes unusual. Oesogastroscopy with biopsy is essential for the
      diagnosis. Food allergies can be involved and must be systematically
      investigated.

PMID- 15738900
TI  - [Auxiliary partial orthotopic liver transplantation using small grafts. A way to
      avoid small-for-size syndrome?].
AB  - If the ratio liver graft weight/recipient body weight ratio is below 0.8%, there
      is a high risk of primary non function of the graft in almost 50% of cases. We
      report the first elective Auxiliary Partial Orthotopic Liver Transplantation
      using a small cadaveric left graft for cirrhosis. The graft weight/recipient body
      weight rate was 0.6%. This technique avoided the small-for-size syndrome in the
      early postoperative period. The native right liver was resected two months later.
      With a follow-up of 5 years, the patient is in good condition. This original
      technique could be a solution to increase the number of transplantations using
      small grafts, especially left grafts, provided by splits or living donors.

PMID- 15738901
TI  - [Post-cholecystectomy amputation neuroma of the common bile duct with obstructive
      jaundice].
AB  - Amputation neuroma of the common bile duct after surgery is a rare and mostly
      asymptomatic lesion. A 60-year old patient presented with obstructive jaundice
      three months after a cholecystectomy for symptomatic gallstones. Imaging
      investigations showed common extrahepatic bile duct stenosis. Surgical resection
      of the stricture with biliodigestive anastomosis was performed. Histological
      examination of the surgical specimen revealed an amputation neuroma. Despite its
      rarity, amputation neuroma of the common bile duct should be considered in
      patients with post-cholecystectomy syndrome following liver or extrahepatic bile
      duct surgical procedures.

PMID- 15738902
TI  - [Splenic infarctus: a rare complication of pancreatic adenocarcinoma].

PMID- 15738903
TI  - [Treatment of oesophageal Crohn's disease by infliximab].

PMID- 15738904
TI  - [Acute pancreatitis secondary to dengue].

PMID- 15738905
TI  - [Hepatitis C related cryoglobulinemia associated with coxsackie virus infection].

PMID- 15738906
TI  - [Acute hepatitis during pregnancy: hepatitis E virus must be considered].

PMID- 15738907
TI  - [Probable sildenafil (Viagra) induced acute hepatitis in a patient with no other
      risk factors].

PMID- 15738908
TI  - Verification of inverse planning and treatment delivery for segmental IMRT.
AB  - With intensity-modulated radiotherapy (IMRT), it is important that the inverse
      planning process yields the most appropriate dose distribution for the patient
      and that the delivered dose then corresponds to the planned dose. This paper
      presents methods by which the inverse planning and delivery of segmental (step
      and-shoot) IMRT can be verified, and gives results for a typical treatment
      planning system (Pinnacle3 v6.2b, Philips Radiation Oncology Systems, Milpitas,
      CA). Inverse planning was assessed by observing the reduction in objective
      function as fields were successively added to three-field prostate, esophagus,
      and thyroid plans. The ability of the treatment planning system to calculate dose
      for a segmented field was examined by creating a stepped field with five
      successively narrowing segments. The complete planning process was then
      investigated by using two orthogonal IMRT fields to create a homogeneous dose
      distribution in a cubic water phantom. Finally, a clinical situation was
      simulated by creating a five-field segmental IMRT plan for a lung target in an
      anthropomorphic phantom. A conformal plan was also compared for context. Addition
      of fields to inverse plans generally resulted in a reduction of objective
      function, indicating consistency of inverse planning solutions. Planned dose for
      fields with stepped intensity agreed with ionization chamber measurements to
      within 5%. For orthogonal fields, planned dose distributions agreed well with
      dose measured using film and agreed with ionization chamber measurements to
      within 3%. For the anthropomorphic phantom, the standard deviation of difference
      between planned and measured dose was 4%. Although no consensus has yet been
      reached on what constitutes an acceptable IMRT plan, these results indicate that
      step-and-shoot IMRT can be planned and delivered using the system described with
      comparable accuracy to a standard conformal treatment.

PMID- 15738910
TI  - Stereotactic IMRT for prostate cancer: setup accuracy of a new stereotactic body
      localization system.
AB  - The purpose of this work is to prospectively assess the setup accuracy that can
      be achieved with a stereotactic body localizer (SBL) in immobilizing patients for
      stereotactic intensity-modulated radiotherapy (IMRT) for prostate cancer. By
      quantifying this important factor and target mobility in the SBL, we expect to
      provide a guideline for selecting planning target volume margins for stereotactic
      treatment planning. We analyzed data from 40 computed tomography (CT) studies
      (with slice thickness of 3 mm) involving 10 patients with prostate cancer. Each
      patient had four sets of CT scans during the course of radiotherapy. For the
      purpose of this study, all four sets of CT scans were obtained with the patients
      immobilized in a customized body pillow formed by vacuum suction. Unlike other
      immobilization devices, this system consists not only of a customized body
      pillow, but also of a fixation sheet used to suppress patient respiratory motion,
      a stereotactic body frame to provide stereotaxy, and a carbon fiber base board to
      which both the body cushion and the frame are affixed. We identified four bony
      landmarks and measured their coordinates in the stereotactic body frame on each
      set of CT scans. The displacements of the bony landmarks from their corresponding
      positions on the simulation scan (first CT scan) were analyzed in three
      dimensions in terms of overall, systematic, and random categories. The initial
      planned isocenter was also marked on the patients' skin with fiducials for each
      CT study. The distance from each bony landmark to the fiducial-based isocenter
      was measured and compared among the four sets of CT scans. The deviations in
      distances were also compared to those measured from the landmarks to the
      stereotactic frame center, in order to determine the effectiveness of the rigid
      body frame in positioning patients with prostate cancer. Target inter-fraction
      motion in this system was also studied for five patients by measuring the
      deviations in distances from the target geometric center to the bony landmarks.
      Our results showed that the overall setup accuracy had standard deviations (SDs)
      of 2.58 mm, 2.41 mm, and 3.51 mm in lateral (LAT), anterior-posterior(AP), and
      superior-inferior (SI) directions, respectively. The random component had SDs of
      1.72 mm, 2.06 mm, and 2.79 mm, and the systematic component showed SDs of 0.92
      mm, -0.27 mm, and 0.90 mm in these three directions. In terms of three
      dimensional vector, the mean displacement over 116 measurements was 3.0 mm with
      an SD of 1.29 mm. Compared to the rigid reference, the skin-mark-based reference
      was less reliable for patient repositioning in terms of reproducing known bony
      landmark positions. The mean target mobility relative to the bony landmarks was
      2.22 +/- 3.45 mm, 0.17 +/- 1.11 mm, and 0.11 +/- 2.69 mm in the AP, LAT, and SI
      directions, respectively. In conclusion, the body immobilization system has the
      ability to immobilize prostate cancer patients with satisfactory setup accuracy
      for fractionated extracranial stereotactic radiotherapy. A rigid frame system
      serves as a reliable alignment reference in terms of repositioning patients into
      the planning position, while skin-based reference showed larger deviations in
      repositioning patients.

PMID- 15738911
TI  - Stereotactic IMRT for prostate cancer: dosimetric impact of multileaf collimator
      leaf width in the treatment of prostate cancer with IMRT.
AB  - The focus of this work is the dosimetric impact of multileaf collimator (MLC)
      leaf width on the treatment of prostate cancer with intensity-modulated radiation
      therapy (IMRT). Ten patients with prostate cancer were planned for IMRT delivery
      using two different MLC leaf widths--4mm and 10mm--representing the Radionics
      micro-multileaf collimator (mMLC) and Siemens MLC, respectively. Treatment
      planning was performed on the XKnifeRT2 treatment-planning system (Radionics,
      Burlington, MA). All beams and optimization parameters were identical for the
      mMLC and MLC plans. All the plans were normalized to ensure that 95% of the
      planning target volume (PTV) received 100% of the prescribed dose. The
      differences in dose distribution between the two different plans were assessed by
      dose-volume histogram (DVH) analysis of the target and critical organs. We
      specifically compared the volume of rectum receiving 40 Gy (V40), 50 Gy (V50), 60
      Gy (V60), the dose received by 17% and 35% of rectum (D17 and D35), and the
      maximum dose to 1 cm3 of the rectum for a prescription dose of 74 Gy. For the
      urinary bladder, the dose received by 25% of bladder (D25), V40, and the maximum
      dose to 1 cm3 of the organ were recorded. For PTV we compared the maximum dose to
      the "hottest" 1 cm3 (Dmax1 cm3) and the dose to 99% of the PTV (D99). The dose
      inhomogeneity in the target, defined as the ratio of the difference in Dmax1 cm3
      and D99 to the prescribed dose, was also compared between the two plans. In all
      cases studied, significant reductions in the volume of rectum receiving doses
      less than 65 Gy were seen using the mMLC. The average decrease in the volume of
      the rectum receiving 40 Gy, 50 Gy, and 60 Gy using the mMLC plans was 40.2%,
      33.4%, and 17.7%, respectively, with p < 0.0001 for V40 and V50 and p < 0.012 for
      V60. The mean dose reductions for D17 and D35 for the rectum using the mMLC were
      20.4% (p < 0.0001) and 18.3% (p < 0.0002), respectively. There were consistent
      reductions in all dose indices studied for the bladder. The target dose
      inhomogeneity was improved in the mMLC plans by an average of 29%. In the high
      dose range, there was no significant difference in the dose deposited in the
      "hottest" 1 cm3 of the rectum between the two plans for all cases (p > 0.78). In
      conclusion, the use of the mMLC for IMRT of the prostate resulted in significant
      improvement in the DVH parameters of the prostate and critical organs, which may
      improve the therapeutic ratio.

PMID- 15738912
TI  - Monte Carlo calculations of output factors for clinically shaped electron fields.
AB  - We report on the use of the EGS4/BEAM Monte Carlo technique to predict the output
      factors for clinically relevant, irregularly shaped inserts as they intercept a
      linear accelerator's electron beams. The output factor for a particular
      combination--energy, cone, insert, and source-to-surface distance (SSD)--is
      defined in accordance with AAPM TG-25 as the product of cone correction factor
      and insert correction factor, evaluated at the depth of maximum dose. Since cone
      correction factors are easily obtained, we focus our investigation on the insert
      correction factors (ICFs). An analysis of the inserts used in routine clinical
      practice resulted in the identification of a set of seven "idealized" shapes
      characterized by specific parameters. The ICFs for these shapes were calculated
      using a Monte Carlo method (EGS4/BEAM) and measured for a subset of them using an
      ion chamber and well-established measurement methods. Analytical models were
      developed to predict the Monte Carlo-calculated ICF values for various electron
      energies, cone sizes, shapes, and SSDs. The goodness-of-fit between predicted and
      Monte Carlo-calculated ICF values was tested using the Kolmogorov-Smirnoff
      statistical test. Results show that Monte Carlo-calculated ICFs match the
      measured values within 2.0% for most of the shapes considered, except for few
      highly elongated fields, where deviations up to 4.0% were recorded. Predicted
      values based on analytical modeling agree with measured ICF values within 2% to
      3% for all configurations. We conclude that the predicted ICF values based on
      modeling of Monte Carlo-calculated values could be introduced in clinical use.

PMID- 15738913
TI  - Real-time motion detection of functional MRI data.
AB  - The objective of this work was to implement a motion-detection algorithm on a
      commercial real-time functional magnetic resonance imaging (fMRI) processing
      package for neurosurgical planning applications. A real-time motion detection
      module was implemented on a commercial real-time processing package. Simulated
      functional data sets with introduced translational, in-plane rotational, and
      through-plane rotational motion were created. The coefficient of variation (COV)
      of the center of intensity was used as a motion quantification metric.
      Coefficients of variation were calculated before and after image registration to
      determine the effectiveness of the motion correction; the limits of
      correctability were also determined. The motion-detection module allowed for real
      time quantification of the motion in an fMRI experiment. Along with knowledge of
      the limits of correctability, this enables determination of whether an experiment
      needs to be reacquired while the patient is in the scanner. This study
      establishes the feasibility of using real-time motion detection for presurgical
      planning fMRI and establishes the limits of correctable motion.

PMID- 15738914
TI  - Surface buildup dose dependence on photon field delivery technique for IMRT.
AB  - The more complex delivery techniques required for implementation of intensity
      modulated radiotherapy (IMRT) based on inverse planning optimization have changed
      the relationship between dose at depth and dose at buildup regions near the
      surface. Surface buildup dose is dependent on electron contamination primarily
      from the unblocked view of the flattening filter and secondarily from air and
      collimation systems. To evaluate the impact of beam segmentation on buildup dose,
      measurements were performed with 10 x 10 cm2 fields, which were delivered with 3
      static 3.5 x 10 cm2 or 3 x 10 cm2 strips, 5 static 2 x 10 cm2 strips, 10 static 1
      x 10 cm2 strips, and 1.1 x 10 cm2 dynamic delivery, compared with a 10 x 10 cm2
      open field. Measurements were performed in water and Solid Water using parallel
      plate chambers, a stereotactic diode, and thermoluminescent dosimeters (TLDs) for
      a 6 MV X-ray beam. Depth doses at 2 mm depth (relative to dose at 10 cm depth)
      were lower by 6%, 7%, 11%, and 10% for the above field delivery techniques,
      respectively, compared to the open field. These differences are most influenced
      by differences in multileaf collimator (MLC) transmission contributing to the
      useful beam. An example IMRT field was also studied to assess variations due to
      delivery technique (static vs. dynamic) and intensity level. Buildup dose is
      weakly dependent on the multileaf delivery technique for efficient IMRT fields.

PMID- 15738915
TI  - Evaluation of an automatic needle-loading system.
AB  - The purpose of this paper is to evaluate the dosimetric capabilities and the
      radiation protection (RP) performance of a new automatic needle-loading system
      for permanent prostate implants, the Isoloader (Mentor Corp.). The unit has been
      used in more than 100 clinical cases at our institution. The Isoloader is a
      computerized workstation that allows automated seed testing by a solid-state
      CdZnTe radiation detector and loading in surgical needles. The seeds are received
      in a shielded and ready-to-use cartridge. Radiation protection measurements were
      done on a cartridge filled with 67 (125)I seeds and during dosimetric seed
      verification and needle loading. The reproducibility of the detector was tested
      and its accuracy was determined by comparison to specified activities of six
      calibration seeds and to their measurements in a calibrated well-chamber (WC).
      Finally, the times required to complete dosimetric verification and needle
      loading were evaluated. The cartridge was found to be adequately shielded, since
      no significant amount of radiation was detected around it. Radiation during seed
      assay was found to be worst at the cartridge's bottom, where it has a value of
      15.2 microSv/h (1.4 microSv/h at 10 cm). For the needle-loading task,
      measurements were performed with a typical needle (three seeds) at the shielded
      needle holder surface yielding 307.2 microSv/h (8.3 microSv/h at 20 cm). Seed
      dosimetric verification takes an average of 15 s/seed, while it takes a mean time
      of 50 s/needle to complete the loading task. Measurements of the six seed
      activities were within 0.65% of the ordered activities and 1.9% higher on average
      than those from the WC (min = 0.7%; max = 3.5%). The reproducibility of the
      measurements of the CdZnTe detector was excellent, with an average of 0.01% of
      deviation from a reference measurement (N = 120; = 1.9%). We therefore conclude
      that the Isoloader is a safe, fast, and effective needle-loading system.

PMID- 15738916
TI  - A dose-volume-based tool for evaluating and ranking IMRT treatment plans.
AB  - External beam radiotherapy is commonly used for patients with cancer. While tumor
      shrinkage and palliation are frequently achieved, local control and cure remain
      elusive for many cancers. With regard to local control, the fundamental problem
      is that radiotherapy-induced normal tissue injury limits the dose that can be
      delivered to the tumor. While intensity-modulated radiation therapy (IMRT) allows
      for the delivery of higher tumor doses and the sparing of proximal critical
      structures, multiple competing plans can be generated based on dosimetric and/or
      biological constraints that need to be considered/compared. In this work, an IMRT
      treatment plan evaluation and ranking tool, based on dosimetric criteria, is
      presented. The treatment plan with the highest uncomplicated target conformity
      index (TCI+) is ranked at the top. The TCI+ is a dose-volume-based index that
      considers both a target conformity index (TCI) and a normal tissue-sparing index
      (NTSI). TCI+ is designed to assist in the process of judging the merit of a
      clinical treatment plan. To demonstrate the utility of this tool, several
      competing lung and prostate IMRT treatment plans are compared. Results show that
      the plan with the highest TCI+ values accomplished the competing goals of tumor
      coverage and critical structures sparing best, among rival treatment plans for
      both treatment sites. The study demonstrates, first, that dose-volume-based
      indices, which summarize complex dose distributions through a single index, can
      be used to automatically select the optimal plan among competing plans, and
      second, that this dose-volume-based index may be appropriate for ranking IMRT
      dose distributions.

PMID- 15738918
TI  - Dosimetric uncertainties of three-dimensional dose reconstruction from two
      dimensional data in a multi-institutional study.
AB  - Inconsistencies in the treatment planning process leading to dosimetric
      uncertainties may affect conclusions drawn from interinstitutional radiation
      oncology clinical trials. The purpose of this study was to assess the dosimetric
      uncertainties resulting from the process of reconstructing three-dimensional dose
      distributions from two-dimensional treatment plan information provided by
      participating institutions in a randomized clinical trial. This study was based
      on American College of Radiology Protocol #427, Locally Advanced Multi-Modality
      Protocol; a multi-institutional phase II randomized study involving radiation
      therapy for patients with inoperable non-small cell lung cancer. Several sources
      of dosimetric uncertainty were identified and analyzed, including image quality
      of hard-copy computed tomography (CT) images, slice spacing of CT scans,
      treatment position, interpretations of target volumes by radiation oncologists,
      the contouring of normal anatomic structures, and the use of common beam models
      for all dose calculations. Each source of uncertainty was investigated using a
      set of plans, with the ideal characteristics of digital images with 3-mm axial
      slice spacing and a flat couch, consisting of eight cases from Vanderbilt
      University Medical Center with electronically transferred CT data. The target
      volume DVH values were dependent on the additional uncertainty introduced by
      differences in delineation of the target volumes by the participating radiation
      oncologists. The DVH values for the lungs and heart were dependent on image
      quality and treatment position. Esophagus DVH values were not dependent on any of
      the sources of uncertainty. None of the structure DVH values were dependent on
      slice thickness or variations in the contouring of normal anatomic structures.
      Reconstruction of three-dimensional dose distributions from two-dimensional
      treatment plan information may be useful in cases for which digital CT data is
      not available or for historical data review. However, dosimetric accuracy will
      depend on image quality of the treatment planning CT data and consistency in the
      delineation of tumor volumes.

PMID- 15738919
TI  - Theoretical foundation for real-time prostate localization using an inductively
      coupled transmitter and a superconducting quantum interference device (SQUID)
      magnetometer system.
AB  - Real-time, 3D localization of the prostate for intensity-modulated radiotherapy
      can be accomplished with passively charged radio frequency transmitters and
      superconducting quantum interference device (SQUID) magnetometers. The overall
      system design consists of an external dipole antenna as a power source for
      charging a microchip implant transmitter and SQUID magnetometers for signal
      detection. An external dipole antenna charges an on-chip capacitor through
      inductive coupling in the near field region through a small implant inductor. The
      charge and discharge sequence between the external antenna and the implant
      circuit can be defined by half duplex, full duplex, or sequential operations. The
      resulting implant discharge current creates an alternating magnetic field through
      the inductor. The field is detected by the surrounding magnetometers, and the
      location of the implant transmitter can be calculated. Problems associated with
      this system design are interrelated with the signal strength at the detectors,
      detector sensitivity, and charge time of the implant capacitor. The physical
      parameters required for optimizing the system for real-time applications are the
      operating frequency, implant inductance and capacitance, the external dipole
      current and loop radius, the detector distance, and mutual inductance.
      Consequently, the sequential operating mode is the best choice for real-time
      localization for constraints requiring positioning within 1 s due to the mutual
      inductance and detector sensitivity. We present the theoretical foundation for
      designing a real-time, 3D prostate localization system including the associated
      physical parameters and demonstrate the feasibility and physical limitations for
      such a system.

PMID- 15738920
TI  - The accuracy of dynamic wedge dose computation in the ADAC Pinnacle RTP system.
AB  - The nonphysical wedge is a modality that uses computer-controlled jaw motion to
      generate wedge-shaped dose distributions. There are Varian enhanced dynamic
      wedges (EDWs) and Siemens virtual wedges (VWs). We recently commissioned dynamic
      wedges on both Varian and Siemens LINACs. The beam data, acquired with a
      Wellhofer chamber array and a Sun Nuclear profiler, are used for modeling in the
      ADAC Pinnacle system. As recommended by ADAC, only a limited number of beam data
      is measured and used for beam modeling. Therefore, the dose distributions of
      dynamic wedges generated by Pinnacle must be examined. Following the
      commissioning of the dynamic wedges, we used Pinnacle to generate a number of
      dose distributions with different energies, wedge angles, field sizes, and
      depths. The computed data from Pinnacle are then compared with the measured data.
      The deviations of the output factor in all square and rectangular fields are
      mostly within 2.0% for both EDW and VW. For asymmetric fields, the deviations are
      within 3%. However, exceptions of differences more than 3% have been found in a
      larger field and large wedge combinations. The precision of the beam profiles
      generated by Pinnacle is also evaluated. As a result of this investigation, we
      present a scope of quality assurance tests that are necessary to ensure
      acceptable consistency between the delivered dose and the associated treatment
      plan when dynamic wedges are applied.

PMID- 15738921
TI  - Comparative evaluation of image quality from three CT simulation scanners.
AB  - Today, radiation therapy (RT) is moving toward increased radiation dose to the
      tumor as a result of 3D conformal RT (3DCRT) and intensity-modulated RT (IMRT),
      which have been made possible by advances in volumetric-based image planning with
      digital imaging systems such as computed tomography (CT). Treatment planning for
      such RT requires superior CT image quality. Our goal in this study was to
      evaluate and to compare the image quality of three unique CT simulation scanners
      available at our center for both single- and multiple-slice helical scanners.
      These scanners included a conventional 70-cm bore single-slice scanner (Philips
      Medical Systems), a large 85-cm bore single-slice scanner (Philips Medical
      Systems), and a 70-cm bore multislice scanner (GE Medical Systems). Image quality
      was evaluated in terms of image noise, low-contrast detectability (LCD), limiting
      spatial resolution (modulation transfer function), and slice thickness accuracy
      in accordance with guidelines set out by the AAPM. A commercially available
      Catphan phantom was used to characterize image quality for both axial and helical
      modes of scanning. We found that image quality was generally comparable for all
      scanners. Limiting spatial resolution and slice thickness accuracy were
      comparable for all three scanners for both scanning modes. The multislice unit
      was superior in terms of noise content, resulting in improved visualization of
      small, low-contrast objects, which is of significant clinical importance,
      particularly for soft tissue delineation. In addition, the multislice unit
      optimizes volume coverage speed and longitudinal resolution without compromising
      image quality, a significant advantage for the radiation oncology environment.

PMID- 15738922
TI  - CT-based analysis of dose homogeneity in total body irradiation using lateral
      beam.
AB  - A computed tomography (CT) based treatment planning system for total body
      irradiation (TBI) is presented and compared with the commonly practiced lateral
      treatment delivery. The TBI regimen has been proved to be an essential
      conditional regimen for patients undergoing bone marrow transplantation. The
      advantage of the TBI regimen with bone marrow transplantation (BMT) in
      hematological malignancies can be offset by toxicities arising from TBI in
      posttransplant complications. With the increasing survival rates, the evaluation
      of long-term side effects and quality of life has become an important area of
      research interest. There have been several treatment techniques developed over
      the decades designed to achieve accurate dose delivery and dose homogeneity. This
      paper reports on the verification of the dose delivery for a basic lateral
      technique using thermoluminescent dosimeters (TLDs) placed in an anthropomorphic
      phantom and its correlation with CT-based treatment planning. CT-based treatment
      plans on several patients were used to evaluate the doses delivered to the whole
      body and critical organs. A large variation in doses delivered to the whole body
      was demonstrated, with some parts of the bone marrow failing to receive the
      prescribed dose and some critical organs, such as the lungs, receiving excessive
      doses. Placing the arms at the sides only partially compensates for the increased
      transmission of the lungs because the arms only shadow part of the lung. This
      study shows that CT-based treatment planning for TBI provides precise and
      accurate dose calculations and allows for the correlation of clinical outcomes
      with the doses actually delivered to various organs.

PMID- 15738923
TI  - Planning quality and delivery efficiency of sMLC delivered IMRT treatment of
      oropharyngeal cancers evaluated by RTOG H-0022 dosimetric criteria.
AB  - The time required to deliver intensity-modulated radiation therapy (IMRT)
      treatments can be significantly longer than conventional treatments, especially
      for the segmented multileaf collimator (sMLC) delivery system with a large record
      and verification (R&V) overhead. In this work, we evaluate the impact of the
      number of intensity-modulated beams (IMBs) and the number of intensity levels
      (ILs) on the quality and delivery efficiency of IMRT plans, generated by the
      Corvus planning system for sMLC delivery on a Siemens LINAC with the Lantis R&V
      system. Detailed studies were performed for three image data sets of previously
      treated oropharyngeal patients. Treatment plans for patient 1 were developed
      using 5, 7, 9, or 15 evenly spaced axial IMBs as well as one with 7 axial IMBs
      whose directions were user-selected, each using ILs of 3, 5, 10, or 20. For
      patients 2 and 3, plans with 15 IMBs and 20 ILs were not attempted. A total of 42
      plans were developed using three oropharyngeal cancer CT image data sets. Plan
      quality was evaluated by assessing compliance with the Radiation Therapy Oncology
      Group (RTOG) H-0022 protocol criteria and the physician's clinical judgment. Plan
      efficiency was accessed by the number of segments of each plan. We found that for
      our treatment-planning and delivery system, an IMRT plan that uses a moderate
      number of IMBs and ILs, such as 7 or 9 IMBs with 3 or 5 ILs, would appear to be
      the optimal approach when both quality of the plan and delivery efficiency are
      considered. Based on this study, we have routinely used 9 IMBs with 3 ILs or 7
      IMBs with 5 ILs for head and neck patients. A retrospective comparison indicates
      that delivery efficiency is improved on the order of 30% compared to plans
      generated with 9 IMBs with 5 ILs.

PMID- 15738924
TI  - MR perfusion measurements on pharyngeal tumors: comparison of quantification
      strategies.
AB  - For the case of pharyngeal carcinomas, the clinical value as well as the
      stability of several evaluation methods of MR tomographic perfusion measurement
      are compared. Eighteen patients suffering from histologically proven squamous
      cell carcinomas were investigated by MR tomography (1.5 T, 0.2 mmol/kg Gd-DTPA)
      prior to and during radiation therapy. Perfusion measurements were performed
      using a double-echo FLASH sequence. Parameters describing regional blood flow,
      blood volume, mean transit time, and interstitial concentration of contrast
      medium (CM) were calculated, applying seven different combinations of correction
      approaches (separating the shortening of T1 and T2*, arterial input function
      (AIF), and tumor shunts). Their correlations to MR independent tumor
      physiological parameters were analyzed (metabolic activity measurements using 18F
      FDG-PET, polarographical pO2 measurement, tumor volume). Significant improvements
      of the correlation between perfusion-dependent and other tumor physiological
      parameters could be achieved by decoupling the shortening of T1 and T2* and by
      applying of the tumor shunt model. Deconvolution from the AIF deteriorated the
      correlation. Therefore, the elimination of the T1 shortening due to interstitial
      CM proves to be essential for MR perfusion measurements on contrast medium
      uptaking lesions. Depending on the measurement conditions (temporal resolution,
      signal-to-noise ratio), the consideration of the AIF can even make the results
      significantly worse by introducing additional measuring errors.

PMID- 15738925
TI  - A tissue-equivalent phantom series for mammography dosimetry.
AB  - A breast tissue-equivalent series (BRTES) of phantoms is manufactured to mimic
      both the attenuation and the density of the range of glandular and adipose tissue
      compositions encountered in mammography. The BRTES simulates breast tissues
      across the range of 20% to 70% glandularity and can be assembled in a variety of
      thicknesses to represent a compressed breast thickness corresponding to
      glandularity to simulate various patient demographics. The fabrication techniques
      are presented, and the physical properties of the completed series of phantoms
      are described. The BRTES phantoms provide a dosimetry comparison with commonly
      used phantoms, including the American College of Radiology accreditation phantom
      and BR12, a 50% glandularity tissue-equivalent material. The comparison shows
      that the average glandular dose is a strong function of compressed breast
      thickness and tissue composition. Patient doses measured using photo-timed
      exposures with the BRTES phantoms can be up to a factor of 3 greater than or less
      than the doses predicted using conventional phantoms.

PMID- 15738926
TI  - Shielding evaluation and acceptance testing of a prefabricated, modular,
      temporary radiation therapy treatment facility.
AB  - We have recently commissioned a temporary radiation therapy facility that is
      novel in two aspects: it was constructed using modular components, and the LINAC
      was installed in one of the modular sections before it was lifted into position.
      Additional steel and granular fill was added to the modular sections on-site
      during construction. The building will be disassembled and removed when no longer
      needed. This paper describes the radiation shielding specifications and survey of
      the facility, as well as the ramifications for acceptance testing occasioned by
      the novel installation procedure. The LINAC is a Varian 21EX operating at 6 MV
      and 18 MV. The radiation levels outside the vault satisfied the design criteria,
      and no anomalous leakage was detected along the joints of the modular structure.
      At 18 MV and 600 monitor units (MU) per minute, the radiation level outside the
      primary barrier walls was 8.5 micro Sv/h of photons; there were no detectable
      neutrons. Outside the direct-shielded door, the levels were 0.4 micro Sv/h of
      photons and 3.0 micro Sv/h of neutrons. The isocentricity of the accelerator met
      the acceptance criteria and was not affected by its preinstallation into an
      integrated baseframe and subsequent transport to the building site.

PMID- 15738927
TI  - Julius Axelrod (1912-2004).

PMID- 15738930
TI  - Controlling false discoveries in candidate gene studies.

PMID- 15738931
TI  - Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing
      energy absorption and increasing fat oxidation.
AB  - OBJECTIVE: To examine the antiobesity effect of epigallocatechin gallate (EGCG),
      a green tea bioactive polyphenol in a mouse model of diet-induced obesity.
      METHODS: Obesity was induced in male New Zealand black mice by feeding of a high
      fat diet. EGCG purified from green tea (TEAVIGO) was supplemented in the diet
      (0.5 and 1%). Body composition (quantitative magnetic resonance), food intake,
      and food digestibility were recorded over a 4-week period. Animals were killed
      and mRNA levels of uncoupling proteins (UCP1-3), leptin, malic enzyme (ME),
      stearoyl-CoA desaturase-1 (SCD1), glucokinase (GK), and pyruvate kinase (PK) were
      analysed in different tissues. Also investigated were acute effects of orally
      administered EGCG (500 mg/kg) on body temperature, activity (transponders), and
      energy expenditure (indirect calorimetry). RESULTS: Dietary supplementation of
      EGCG resulted in a dose-dependent attenuation of body fat accumulation. Food
      intake was not affected but faeces energy content was slightly increased by EGCG,
      indicating a reduced food digestibility and thus reduced long-term energy
      absorption. Leptin and SCD1 gene expression in white fat was reduced but SCD1 and
      UCP1 expression in brown fat was not changed. In liver, gene expression of SCD1,
      ME, and GK was reduced and that of UCP2 increased. Acute oral administration of
      EGCG over 3 days had no effect on body temperature, activity, and energy
      expenditure, whereas respiratory quotient during night (activity phase) was
      decreased, supportive of a decreased lipogenesis and increased fat oxidation.
      CONCLUSIONS: Dietary EGCG attenuated diet-induced body fat accretion in mice.
      EGCG apparently promoted fat oxidation, but its fat-reducing effect could be
      entirely explained by its effect in reducing diet digestibility.

PMID- 15738932
TI  - Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and
      cost-effectiveness as rationales for reimbursement in Sweden and Switzerland.
AB  - OBJECTIVE: The aim of this study is to review the clinical and economic rationale
      for the reimbursement of orlistat in responding obese patients with type 2
      diabetes. METHODS: Data from seven randomized controlled clinical trials of
      orlistat in overweight and obese patients with type 2 diabetes were pooled. A
      subgroup analysis involving patients who achieved a response (defined as a weight
      loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the
      pooled analysis were then used to construct a Markov health economic model
      covering an 11-y period. The incidences of diabetes-related micro- and
      macrovascular complications were derived from the United Kingdom Prospective
      Diabetes Study. The effects of changes in body mass index, and the impact of
      micro- and macrovascular complications on utilities were derived from published
      sources. Publicly available cost data were used and are presented here in 2001
      Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was
      conducted to examine the robustness of results. RESULTS: A total of 1249 patients
      treated with orlistat and 1230 given placebo were eligible for the intent-to
      treat analysis. At the end of the study period, 23% of orlistat patients achieved
      a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of
      1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and
      a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic
      analysis revealed costs per quality-adjusted life year gained of euro14 000 in
      Sweden and euro13 600 in Switzerland. CONCLUSION: The data presented here support
      the utilization and reimbursement of orlistat in overweight and obese diabetic
      patients who respond to the treatment.

PMID- 15738933
TI  - Post-treatment phone contact: a weight maintenance strategy in obese youngsters.
AB  - This study investigated the effect of post-treatment phone contact on weight-loss
      maintenance and activity behaviour in obese youngsters. In all, 20 patients who
      completed a weight reduction program were randomly assigned to a 5-month
      maintenance programme (experimental) or control condition. Following the
      maintenance programme, patients sent a weekly activity diary to the therapist,
      who in turn phoned them biweekly to discuss their activities. Body weight,
      stature and physical activity were measured before and after the maintenance
      programme. The control group showed a continuous increase in overweight after
      initial treatment, while the experimental group showed a steep increase during
      the summer holidays (no intervention), but this increase slowed down during the
      maintenance programme (P<0.05). Moderate-to-high intensity activities increased
      during the maintenance programme in the experimental group, but decreased in the
      control group (P<0.001). In conclusion, post-treatment phone contact appears to
      have the potential to be an effective maintenance strategy in obese youngsters.

PMID- 15738934
TI  - Adiposity induced by adenovirus 5 inoculation.
AB  - OBJECTIVE: To investigate the effect of viral inoculation by adenovirus 5 (Ad5)
      on body composition in a mouse model. DESIGN: Longitudinal monitoring before and
      after a single injection of virus or saline. SUBJECTS: Two groups of CD1 mice,
      one group given a single intraperitoneal dose of Ad5 and the control group,
      saline. MEASUREMENTS: Bodyweights and food intake were recorded before and up to
      21 weeks after inoculation. At the end of the study, whole-body 1H magnetic
      resonance spectroscopy (MRS) and localised in vivo 1H MRS spectroscopy of the
      liver was performed to assess whole-body adiposity and intrahepatic lipid
      content, respectively. RESULTS: Ad5-treated animals gained significantly more
      weight over a period of 21 weeks after inoculation than the controls, 21.8 g
      (18.8-25.0) and 18.8 g (17.3-19.8) respectively, (P<0.05). The gain in bodyweight
      in the former animals arises from increased deposition of adipose tissue as
      measured by whole-body 1H MRS. Adiposity was 6.7% (3.10-11.20%), and 2.40% (0.85
      5.65%) for the Ad5-treated and control animals, respectively (P<0.05). No
      significant difference in intrahepatic lipid content or food intake was observed
      between the two groups. CONCLUSION: The significantly higher percentage of
      adipose tissue in the Ad5-treated mice suggest viral infection may play a
      contributory role to a predisposition to obesity, although its contribution
      relative to other factors remains to be determined.

PMID- 15738935
TI  - Variation at the DRD4 promoter modulates extraversion in Caucasians.

PMID- 15738936
TI  - Evidence for linkage to chromosome 13q32 in an independent sample of
      schizophrenia families.

PMID- 15738941
TI  - Biocomposites: using light to drive biosynthesis.

PMID- 15738943
TI  - Photochromic materials: a molecular cushion for isomerization.

PMID- 15738946
TI  - In vitro inhibition of angiogenesis by prostasomes.
AB  - Prostasomes are biologically active organelles that are secreted by human
      prostate epithelial cells, and it is believed that they have a role in prostatic
      disease. We studied the effect of prostasomes on the human umbilical vein
      endothelial cell (HUVEC)/Matrigel model of angiogenesis, and the association of
      labelled prostasomes with HUVECs. The growth inhibitory effect of prostasomes on
      HUVECs was assayed by spectrophotometric measurement of residual biomass.
      Preparations of HUVECs on a Matrigel base were exposed to prostasomes, and the
      development of capillary-like networks was quantified. Prostasomes were labelled
      with PKH-26, and cultured with HUVECs. Prostasomes were not shown to have a
      significant effect on HUVEC survival. Angiogenesis assays showed inhibition. The
      PKH-26-labelled particles were shown to have adhered to the HUVECs. This study
      adds the inhibition of an in vitro correlate of angiogenesis to the known actions
      of prostasomes.

PMID- 15738947
TI  - Functional analysis of genetic variants in the human concentrative nucleoside
      transporter 3 (CNT3; SLC28A3).
AB  - The human concentrative nucleoside transporter, CNT3 (SLC28A3), plays an
      important role in mediating the cellular entry of a broad array of physiological
      nucleosides and synthetic anticancer nucleoside analog drugs. As a first step
      toward understanding the genetic basis for interindividual differences in the
      disposition and response to antileukemic nucleoside analogs, we examined the
      genetic and functional diversity of CNT3. In all, 56 variable sites in the exons
      and flanking intronic region of SLC28A3 were identified in a collection of 270
      DNA samples from US populations (80 African-Americans, 80 European-Americans, 60
      Asian-Americans, and 50 Mexican-Americans). Of the 16 coding region variants, 12
      had not been previously reported. Also, 10 resulted in amino-acid changes and
      three of these had total allele frequencies of >/=1%. Nucleotide diversity (pi)
      at nonsynonymous and synonymous sites was estimated to be 1.81 x 10(4) and 18.13
      x 10(4), respectively, suggesting that SLC28A3 is under negative selection. All
      nonsynonymous variants, constructed by site-directed mutagenesis and expressed in
      Xenopus laevis oocytes, transported purine and pyrimidine model substrates,
      except for c. 1099G>A (p. Gly367Arg). This rare variant alters an evolutionarily
      conserved site in the putative substrate recognition domain of CNT3. The presence
      of three additional evolutionarily conserved glycine residues in the vicinity of
      p. Gly367Arg that are also conserved in human paralogs suggest that these glycine
      residues are critical in the function of the concentrative nucleoside transporter
      family. The genetic analysis and functional characterization of CNT3 variants
      suggest that this transporter does not tolerate nonsynonymous changes and is
      important for human fitness.

PMID- 15738949
TI  - Alternatives to binary fission in bacteria.
AB  - Whereas most prokaryotes rely on binary fission for propagation, many species use
      alternative mechanisms, which include multiple offspring formation and budding,
      to reproduce. In some bacterial species, these eccentric reproductive strategies
      are essential for propagation, whereas in others the programmes are used
      conditionally. Although there are tantalizing images and morphological
      descriptions of these atypical developmental processes, none of these
      reproductive structures are characterized at the molecular genetic level. Now,
      with newly available analytical techniques, model systems to study these
      alternative reproductive programmes are being developed.

PMID- 15738950
TI  - Protein glycosylation in bacterial mucosal pathogens.
AB  - In eukaryotes, glycosylated proteins are ubiquitous components of extracellular
      matrices and cellular surfaces. Their oligosaccharide moieties are implicated in
      a wide range of cell-cell and cell-matrix recognition events that are required
      for biological processes ranging from immune recognition to cancer development.
      Glycosylation was previously considered to be restricted to eukaryotes; however,
      through advances in analytical methods and genome sequencing, there have been
      increasing reports of both O-linked and N-linked protein glycosylation pathways
      in bacteria, particularly amongst mucosal-associated pathogens. Studying
      glycosylation in relatively less-complicated bacterial systems provides the
      opportunity to elucidate and exploit glycoprotein biosynthetic pathways. We will
      review the genetic organization, glycan structures and function of glycosylation
      systems in mucosal bacterial pathogens, and speculate on how this knowledge may
      help us to understand glycosylation processes in more complex eukaryotic systems
      and how it can be used for glycoengineering.

PMID- 15738951
TI  - Acidocalcisomes - conserved from bacteria to man.
AB  - Recent work has shown that acidocalcisomes, which are electron-dense acidic
      organelles rich in calcium and polyphosphate, are the only organelles that have
      been conserved during evolution from prokaryotes to eukaryotes. Acidocalcisomes
      were first described in trypanosomatids and have been characterized in most
      detail in these species. Acidocalcisomes have been linked with several functions,
      including storage of cations and phosphorus, polyphosphate metabolism, calcium
      homeostasis, maintenance of intracellular pH homeostasis and osmoregulation.
      Here, we review acidocalcisome ultrastructure, composition and function in
      different trypanosomatids and other organisms.

PMID- 15738948
TI  - Poxvirus tropism.
AB  - Despite the success of the WHO-led smallpox eradication programme a quarter of a
      century ago, there remains considerable fear that variola virus, or other related
      pathogenic poxviruses such as monkeypox, could re-emerge and spread disease in
      the human population. Even today, we are still mostly ignorant about why most
      poxvirus infections of vertebrate hosts show strict species specificity, or how
      zoonotic poxvirus infections occur when poxviruses occasionally leap into novel
      host species. Poxvirus tropism at the cellular level seems to be regulated by
      intracellular events downstream of virus binding and entry, rather than at the
      level of specific host receptors as is the case for many other viruses. This
      review summarizes our current understanding of poxvirus tropism and host range,
      and discusses the prospects of exploiting host-restricted poxvirus vectors for
      vaccines, gene therapy or tissue-targeted oncolytic viral therapies for the
      treatment of human cancers.

PMID- 15738952
TI  - Immunology of hepatitis B virus and hepatitis C virus infection.
AB  - More than 500 million people worldwide are persistently infected with the
      hepatitis B virus (HBV) and/or hepatitis C virus (HCV) and are at risk of
      developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite
      many common features in the pathogenesis of HBV- and HCV-related liver disease,
      these viruses markedly differ in their virological properties and in their immune
      escape and survival strategies. This review assesses recent advances in our
      understanding of viral hepatitis, contrasts mechanisms of virus-host interaction
      in acute hepatitis B and hepatitis C, and outlines areas for future studies.

PMID- 15738953
TI  - Regulation of plasma-cell development.
AB  - Plasma cells are the terminally differentiated, non-dividing effector cells of
      the B-cell lineage. They are cellular factories devoted to the task of
      synthesizing and secreting thousands of molecules of clonospecific antibody each
      second. To respond to microbial pathogens with the necessary specificity and
      rapidity, B cells are exquisitely regulated with respect to both development in
      the bone marrow and activation in the periphery. This review focuses on the
      terminal differentiation of B cells into plasma cells, including the different
      subsets of B cells that become plasma cells, the mechanism of regulation of this
      transition, the transcription factors that control each developmental stage and
      the characteristics of long-lived plasma cells.

PMID- 15738954
TI  - Stress-induced immune dysfunction: implications for health.
AB  - Folk wisdom has long suggested that stressful events take a toll on health. The
      field of psychoneuroimmunology (PNI) is now providing key mechanistic evidence
      about the ways in which stressors--and the negative emotions that they generate-
      can be translated into physiological changes. PNI researchers have used animal
      and human models to learn how the immune system communicates bidirectionally with
      the central nervous and endocrine systems and how these interactions impact on
      health.

PMID- 15738955
TI  - Consensual immunity: success-driven development of T-helper-1 and T-helper-2
      responses.
AB  - Non-germline-encoded T- and B-cell receptors allow humans to effectively deal
      with rapidly mutating pathogens. Here, we argue that, in addition to determining
      the antigenic specificity of immune responses, the same receptor systems can also
      regulate the T-helper-1/T-helper-2 profile of immunity. Such a mechanism--based
      on feedback from distinct effector cells to dendritic cells, rather than on
      instruction from pathogens--uses the effectiveness of particular effector cells
      at targeting and destroying a pathogen as a reliable, experience-based criterion
      to induce and maintain the appropriately polarized response.

PMID- 15738956
TI  - Expression and functions of neuronal gap junctions.
AB  - Gap junctions are channel-forming structures in contacting plasma membranes that
      allow direct metabolic and electrical communication between almost all cell types
      in the mammalian brain. At least 20 connexin genes and 3 pannexin genes probably
      code for gap junction proteins in mice and humans. Gap junctions between murine
      neurons (also known as electrical synapses) can be composed of connexin 36,
      connexin 45 or connexin 57 proteins, depending on the type of neuron.
      Furthermore, pannexin 1 and 2 are likely to form electrical synapses. Here, we
      discuss the roles of connexin and pannexin genes in the formation of neuronal gap
      junctions, and evaluate recent functional analyses of electrical synapses that
      became possible through the characterization of mouse mutants that show targeted
      defects in connexin genes.

PMID- 15738957
TI  - Variations on an inhibitory theme: phasic and tonic activation of GABA(A)
      receptors.
AB  - The proper functioning of the adult mammalian brain relies on the orchestrated
      regulation of neural activity by a diverse population of GABA (gamma-aminobutyric
      acid)-releasing neurons. Until recently, our appreciation of GABA-mediated
      inhibition focused predominantly on the GABA(A) (GABA type A) receptors located
      at synaptic contacts, which are activated in a transient or 'phasic' manner by
      GABA that is released from synaptic vesicles. However, there is growing evidence
      that low concentrations of ambient GABA can persistently activate certain
      subtypes of GABA(A) receptor, which are often remote from synapses, to generate a
      'tonic' conductance. In this review, we consider the distinct roles of synaptic
      and extrasynaptic GABA receptor subtypes in the control of neuronal excitability.

PMID- 15738958
TI  - The floor plate: multiple cells, multiple signals.
AB  - One of the key organizers in the CNS is the floor plate - a group of cells that
      is responsible for instructing neural cells to acquire distinctive fates, and
      that has an important role in establishing the elaborate neuronal networks that
      underlie the function of the brain and spinal cord. In recent years, considerable
      controversy has arisen over the mechanism by which floor plate cells form. Here,
      we describe recent evidence that indicates that discrete populations of floor
      plate cells, with characteristic molecular properties, form in different regions
      of the neuraxis, and we discuss data that imply that the mode of floor plate
      induction varies along the anteroposterior axis.

PMID- 15738959
TI  - Is mood chemistry?
AB  - The chemical hypothesis of depression suggests that mood disorders are caused by
      a chemical imbalance in the brain, which can be corrected by antidepressant
      drugs. However, recent evidence indicates that problems in information processing
      within neural networks, rather than changes in chemical balance, might underlie
      depression, and that antidepressant drugs induce plastic changes in neuronal
      connectivity, which gradually lead to improvements in neuronal information
      processing and recovery of mood.

PMID- 15738960
TI  - Imaging implicit perception: promise and pitfalls.
AB  - The study of implicit perception - perception in the absence of awareness - has a
      long history. Decades of behavioural work have identified crucial theoretical and
      methodological issues that must be considered when evaluating claims of implicit
      perception. Neuroimaging methods provide an important new avenue for illuminating
      our understanding of perception both with and without awareness, but most imaging
      experiments have not met the rigorous conditions that the behavioural work has
      shown are necessary for inferring implicit perception. Here, we review the
      literature of both behavioural and neuroimaging studies, and note the pitfalls of
      studying implicit perception as well as the promise that neuroimaging studies
      have for providing insights about implicit perception when combined with
      appropriately rigorous behavioural measures of awareness.

PMID- 15738961
TI  - Emerging technologies for gene manipulation in Drosophila melanogaster.
AB  - The popularity of Drosophila melanogaster as a model for understanding eukaryotic
      biology over the past 100 years has been accompanied by the development of
      numerous tools for manipulating the fruitfly genome. Here we review some recent
      technologies that will allow Drosophila melanogaster to be manipulated more
      easily than any other multicellular organism. These developments include the
      ability to create molecularly designed deletions, improved genetic mapping
      technologies, strategies for creating targeted mutations, new transgenic
      approaches and the means to clone and modify large fragments of DNA.

PMID- 15738962
TI  - Research resources for Drosophila: the expanding universe.
AB  - Drosophila melanogaster has been the subject of research into central questions
      about biological mechanisms for almost a century. The experimental tools and
      resources that are available or under development for D. melanogaster and its
      related species, particularly those for genomic analysis, are truly outstanding.
      Here we review three types of resource that have been developed for D.
      melanogaster research: databases and other sources of information, biological
      materials and experimental services. These resources are there to be exploited
      and we hope that this guide will encourage new uses for D. melanogaster
      information, materials and services, both by those new to flies and by
      experienced D. melanogaster researchers.

PMID- 15738963
TI  - The centrosome in human genetic disease.
AB  - The centrosome is an indispensable component of the cell-cycle machinery of
      eukaryotic cells, and the perturbation of core centrosomal or centrosome
      associated proteins is linked to cell-cycle misregulation and cancer. Recent work
      has expanded our understanding of the functional complexity and importance of
      this organelle. The centrosomal localization of proteins that are involved in
      human genetic disease, and the identification of novel centrosome-associated
      proteins, has shown that numerous, seemingly unrelated, cellular processes can be
      perturbed by centrosomal dysfunction. Here, we review the mechanistic
      relationship between human disease phenotypes and the function of the centrosome,
      and describe some of the newly-appreciated functions of this organelle in animal
      cells.

PMID- 15738964
TI  - Folic acid - vitamin and panacea or genetic time bomb?
AB  - We live in a health-conscious age - many of us supplement our diet with essential
      micronutrients through the discretionary use of multivitamin pills or judicious
      selection of foods that have a health benefit beyond that conferred by the
      nutrient content alone - the so-called 'functional foods'. Indeed, the citizens
      of some nations have little choice, with a mandatory fortification policy in
      place for certain vitamins. But do we ever stop to consider the consequences of
      an increased exposure to micronutrients? We examine this issue in relation to the
      B-group vitamin folic acid, and ask whether supplementation with this vitamin
      could introduce a strong genetic selection pressure - one that has the side
      effect of increasing the prevalence of some of the most significant, human life
      threatening diseases. Are we affecting our genetics - is this a case of human
      evolution in progress by altering our diet?

PMID- 15738965
TI  - Pharmacogenetics and geographical ancestry: implications for drug development and
      global health.
AB  - Understanding and harnessing genomic variation will contribute significantly to
      improving the health of people in developing countries. We need to explore the
      nexus between pharmacogenetics, genotyping projects in developing countries, and
      the evolution of the pharmaceutical industry in both the developed and developing
      worlds. Here, we argue that, for the foreseeable future, we should focus not on
      boutique 'personalized' medicine, but on carefully defined differences between
      populations and ethical ways of using emerging genomics knowledge to develop
      drugs and improve health.

PMID- 15738967
TI  - Pars and polarity: taking control of Rac.

PMID- 15738968
TI  - Cdc48-Ufd2-Rad23: the road less ubiquitinated?

PMID- 15738969
TI  - An endocytic Prk-ing brake.

PMID- 15738970
TI  - Growth factor control of autophagy.

PMID- 15738971
TI  - Stress and death: breaking up the c-Abl/14-3-3 complex in apoptosis.

PMID- 15738972
TI  - The Myc trilogy: lord of RNA polymerases.

PMID- 15738973
TI  - Nucleolar targeting runs on GTP cycles.

PMID- 15738974
TI  - Spindle assembly: asters part their separate ways.
AB  - Cells have developed diverse ways to separate two microtubule asters to form a
      mitotic spindle. Here, I focus on two mechanisms used to position asters around
      chromosomes during mitosis: first, aster migration around the nuclear envelope
      and, second, aster attachment to a contractile cortex at the plasma membrane
      after the nuclear envelope has broken down. Although certain cell types use one
      mechanism predominantly, most rely on both to ensure proper spindle assembly.

PMID- 15738976
TI  - Imaging of single light-responsive clock cells reveals fluctuating free-running
      periods.
AB  - Zebrafish tissues and cell lines contain circadian clocks that respond directly
      to light. Using fluorescence-activated cell sorting, we have isolated clonal cell
      lines that contain the reporter construct, zfperiod4-luciferase. Bioluminescent
      assays show that oscillations within cell populations are dampened in constant
      darkness. However, single-cell imaging reveals that individual cells continue to
      oscillate, but with widely distributed phases and marked stochastic fluctuations
      in free-running period. Because these cells are directly light responsive, we can
      easily follow phase shifts to single light pulses. Here we show that light acts
      to reset desynchronous cellular oscillations to a common phase, as well as
      stabilize the subsequent free-running period.

PMID- 15738977
TI  - HDL as a target in the treatment of atherosclerotic cardiovascular disease.
AB  - Lipid abnormalities are among the key risk factors for cardiovascular disease.
      Indeed, lipid-modifying drugs - in particular, the statins, which primarily lower
      plasma levels of low-density lipoprotein (LDL) cholesterol - considerably reduce
      the risk of cardiovascular events, leading to their widespread use. Nevertheless,
      it seems that there might be limits to the degree of benefit that can be achieved
      by lowering LDL-cholesterol levels alone, which has led to increased interest in
      targeting other lipid-related risk factors for cardiovascular disease, such as
      low levels of high-density lipoprotein (HDL) cholesterol. In this article, we
      first consider the mechanisms that underlie the protective effect of HDL
      cholesterol, and then discuss several strategies that have recently emerged to
      increase levels of HDL cholesterol to treat cardiovascular disease, including
      nuclear receptor modulation, inhibition of cholesteryl ester transfer protein and
      infusion of apolipoprotein/phospholipid complexes.

PMID- 15738978
TI  - Therapeutic applications of polymeric artificial cells.
AB  - Polymeric artificial cells have the potential to be used for a wide variety of
      therapeutic applications, such as the encapsulation of transplanted islet cells
      to treat diabetic patients. Recent advances in biotechnology, molecular biology,
      nanotechnology and polymer chemistry are now opening up further exciting
      possibilities in this field. However, it is also recognized that there are
      several key obstacles to overcome in bringing such approaches into routine
      clinical use. This review describes the historical development and principles
      behind polymeric artificial cells, the present state of the art in their
      therapeutic application, and the promises and challenges for the future.

PMID- 15738979
TI  - Reporter mice and drug discovery and development.
AB  - In vivo reporter gene and imaging technologies have the potential to contribute
      to the drug discovery pipeline in several areas. They provide systems that enable
      the study of the biochemical activity of a target in disease, and in response to
      a drug, to be monitored over periods of time, and offer more accurate methods of
      measuring pharmacodynamics and toxicity. Although reporter-gene technology is in
      its infancy, with further refinement reporter animals could become a valuable
      tool in the early stages of target and lead identification and preclinical drug
      development.

PMID- 15738980
TI  - Healing sound: the use of ultrasound in drug delivery and other therapeutic
      applications.
AB  - Ultrasound, which is routinely used for diagnostic imaging applications, is now
      being adopted in various drug delivery and other therapeutic applications.
      Ultrasound has been shown to facilitate the delivery of drugs across the skin,
      promote gene therapy to targeted tissues, deliver chemotherapeutic drugs into
      tumours and deliver thrombolytic drugs into blood clots. In addition, ultrasound
      has also been shown to facilitate the healing of wounds and bone fractures. This
      article reviews the principles and current status of ultrasound-based treatments.

PMID- 15738981
TI  - Cancer nanotechnology: opportunities and challenges.
AB  - Nanotechnology is a multidisciplinary field, which covers a vast and diverse
      array of devices derived from engineering, biology, physics and chemistry. These
      devices include nanovectors for the targeted delivery of anticancer drugs and
      imaging contrast agents. Nanowires and nanocantilever arrays are among the
      leading approaches under development for the early detection of precancerous and
      malignant lesions from biological fluids. These and other nanodevices can provide
      essential breakthroughs in the fight against cancer.

PMID- 15738982
TI  - The promise of genetically engineered mice for cancer prevention studies.
AB  - Sophisticated genetic technologies have led to the development of mouse models of
      human cancers that recapitulate important features of human oncogenesis. Many of
      these genetically engineered mouse models promise to be very relevant and
      relatively rapid systems for determining the efficacy of chemopreventive agents
      and their mechanisms of action. The validation of such models for chemoprevention
      will help the selection of appropriate agents for large-scale clinical trials and
      allow the testing of combination therapies.

PMID- 15738983
TI  - Colorectal cancer screening: prospects for molecular stool analysis.
AB  - Colorectal cancer is common. As many patients present with advanced disease, an
      effective screening test would have substantial clinical benefits. Recent
      progress in understanding the biology of colorectal cancer (and of cancer cells
      in general) has led to possible new approaches to screening. In particular, there
      are prospects of developing tests based on analysis of stool, which promise
      improved accuracy, safety, affordability and patient compliance.

PMID- 15738984
TI  - Testicular germ-cell tumours in a broader perspective.
AB  - The germ-cell tumours are a fascinating group of neoplasms because of their
      unusual biology and the spectacular therapeutic results that have been obtained
      in these tumours. Traditionally, this group of neoplasms is presented in an organ
      oriented approach. However, recent clinical and experimental data convincingly
      demonstrate that these neoplasms are one disease with separate entities that can
      manifest themselves in different anatomical sites. We propose five entities, in
      which the developmental potential is determined by the maturation stage and
      imprinting status of the originating germ cell. Recent progress begins to explain
      the apparent unpredictable development of germ-cell tumours and offers a basis
      for understanding their exquisite sensitivity to therapy.

PMID- 15738985
TI  - The role of apoptosis in cancer development and treatment response.
AB  - The inactivation of programmed cell death, or apoptosis, is central to the
      development of cancer. This disabling of apoptotic responses might be a major
      contributor both to treatment resistance and to the observation that, in many
      tumours, apoptosis is not the main mechanism for the death of cancer cells in
      response to common treatment regimens. Importantly, this suggests that other
      modes of cell death are involved in the response to therapy.

PMID- 15738986
TI  - Intrinsically unstructured proteins and their functions.
AB  - Many gene sequences in eukaryotic genomes encode entire proteins or large
      segments of proteins that lack a well-structured three-dimensional fold.
      Disordered regions can be highly conserved between species in both composition
      and sequence and, contrary to the traditional view that protein function equates
      with a stable three-dimensional structure, disordered regions are often
      functional, in ways that we are only beginning to discover. Many disordered
      segments fold on binding to their biological targets (coupled folding and
      binding), whereas others constitute flexible linkers that have a role in the
      assembly of macromolecular arrays.

PMID- 15738987
TI  - Lipid traffic: floppy drives and a superhighway.
AB  - Understanding how membrane lipids achieve their non-random distribution in cells
      is a key challenge in cell biology at present. In addition to being sorted into
      vesicles that can cross distances of up to one metre, there are other mechanisms
      that mediate the transport of lipids within a range of a few nanometres. These
      include transbilayer flip-flop mechanisms and transfer across narrow gaps between
      the endoplasmic reticulum and other organelles, with the endoplasmic reticulum
      functioning as a superhighway along which lipids can rapidly diffuse.

PMID- 15738988
TI  - Organization of vesicular trafficking in epithelia.
AB  - Experiments using mammalian epithelial cell lines have elucidated biosynthetic
      and recycling pathways for apical and basolateral plasma-membrane proteins, and
      have identified components that guide apical and basolateral proteins along these
      pathways. These components include apical and basolateral sorting signals,
      adaptors for basolateral signals, and docking and fusion proteins for vesicular
      trafficking. Recent live-cell-imaging studies provide a real-time view of sorting
      processes in epithelial cells, including key roles for actin, microtubules and
      motors in the organization of post-Golgi trafficking.

PMID- 15738989
TI  - The mitochondrial uncoupling-protein homologues.
AB  - Uncoupling protein(UCP)1 is an integral membrane protein that is located in the
      mitochondrial inner membrane of brown adipocytes. Its physiological role is to
      mediate a regulated, thermogenic proton leak. UCP2 and UCP3 are recently
      identified UCP1 homologues. They also mediate regulated proton leak, and might
      function to control the production of superoxide and other downstream reactive
      oxygen species. However, their role in normal physiology remains unknown. Recent
      studies have shown that UCP2 has an important part in the pathogenesis of type-2
      diabetes. The obscure roles of the UCP homologues in normal physiology, together
      with their emerging role in pathophysiology, provide exciting potential for
      further investigation.

PMID- 15738990
TI  - Do peptides control their own birth and death?
AB  - The tumour suppressor protein p53 and the Epstein-Barr-virus-encoded Epstein-Barr
      virus nuclear antigen-1 (EBNA1) can regulate their own proteasomal degradation
      and mRNA translation - in effect, they mediate control of their own steady-state
      levels. A large fraction of mRNA-translation-initiation events does not give rise
      to functional proteins; so could this reflect a more widespread concept by which
      certain proteins that require tight control of expression use similar means of
      self-regulation?

PMID- 15738991
TI  - Photothermal sensitisation: evidence for the lack of oxygen effect on the
      photosensitising activity.
AB  - Irradiation of amelanotic melanoma B78H1 cells in the presence of liposome
      delivered Ni(II)-octabutoxy-naphthalocyanine with a Q-switched Ti:sapphire laser
      operated in a pulsed mode (850 nm, 30 ns pulses, 10 Hz, 120 mJ pulse -1) promotes
      a photothermal sensitization process leading to extensive cell inactivation. The
      photoprocess occurs with identical efficiency in N2-saturated and air
      equilibrated media, indicating that this photosensitization modality does not
      require the presence of oxygen.

PMID- 15738992
TI  - Synthesis and spectroscopic characterisation of new ESIPT fluorescent protein
      probes.
AB  - Three new benzazole isothiocyanate fluorescent dyes, 2-(4'-isothiocyanate-2'
      hydroxyphenyl)benzoxazole, 2-(4'-isothiocyanate-2'-hydroxyphenyl)benzothiazole
      and 2-(4'-isothiocyanate-2'-hydroxyphenyl)benzimidazole were synthesised,
      purified until optical purity grade and characterised by spectroscopic
      techniques. UV/VIS and steady-state fluorescence were also applied to
      characterise the photophysical behaviour of the dyes. These dyes exhibit an
      intense fluorescence emission with a large Stokes shift, inherent to the class of
      benzazoles which relax by the excited state intramolecular proton transfer
      (ESIPT) mechanism. The dyes were studied for labeling bovine serum albumin (BSA),
      resulting conjugates BSA-dye with a remarkable photostability under UV/VIS
      radiation in relation to classical protein labels. The resulting conjugates
      presented fluorescence in the blue-green region. Direct fluorescence detection of
      protein-labeled with those dyes after polyacrylamide gel electrophoresis
      indicates their potential use as fluorescent probes for proteins.

PMID- 15738993
TI  - Excited-state dynamics of the fluorescent probe Lucifer Yellow in liquid
      solutions and in heterogeneous media.
AB  - The photophysics of the dye Lucifer Yellow ethylenediamine (LYen) has been
      investigated in various polar solvents. The main deactivation pathways of its
      first singlet excited state are the fluorescence and the intersystem crossing. In
      water, non-radiative decay by intermolecular proton transfer becomes a
      significant deactivation channel. The early fluorescence dynamics, which was
      investigated in liquids and in reverse micelles, was found to depend
      substantially on the environment. An important static quenching of LYen by
      tryptophan and indole occurring in the subpicosecond timescale was observed. The
      use of the fluorescence dynamics of LYen as a local probe is illustrated by
      preliminary results obtained with a biotinylated Lucifer Yellow derivative
      complexed with avidin.

PMID- 15738994
TI  - Kinetics and mechanism of the sensitized photodegradation of lignin model
      compounds.
AB  - The kinetics of the sensitized photodegradation of a variety of well-defined
      lignin model compounds was studied to determine the mechanisms responsible for
      lignin's photochemically-mediated oxidation. Monomeric and dimeric models
      representing lignin's phenolic end groups and nonphenolic dimers representing its
      inner core were studied. It was determined that the rate constants for the
      reaction of the deprotonated phenolic models with singlet oxygen (1O2) range from
      0.96 to 7.2 x 10(7) M(-1) s(-1). The models were substituted with zero, one, or
      two electron-donating methoxy groups on both aryl rings and, while the rate
      constants showed little dependence on the substitution of the nonphenolic ring,
      the rate constants increased dramatically with increasing methoxy substitution of
      the phenol. Reaction between these deprotonated models and 1O2 is thus proposed
      to occur at the phenolate ring. Under neutral conditions, it was observed that
      the phenolic models react with excited state sensitizer, with this reaction also
      occuring at the phenol ring. The sum of the rate constants for quenching of and
      reaction with excited state sensitizer by lignin model compound ranges from 5.4
      to 75 x 10(7) M(-1) s(-1). This study corrects previous reports that attribute
      the sensitized degradation of neutral lignin model compounds to reaction with
      1O2. A nonphenolic aromatic ketone inner-core model was observed to undergo
      direct photolysis, and its reduced analog was not degraded by direct photolysis
      or reaction with 1O2 or excited state sensitizer. The oxidized inner-core model
      was also shown to be able to act as a sensitizer for the degradation of a
      phenolic lignin model compound.

PMID- 15738996
TI  - Photodynamics of excitation energy transfer in self-assembled dyads. Evidence for
      back transfer.
AB  - Three self-assembled photonic dyads comprising a zinc porphyrin donor and a free
      base acceptor have been studied by time-resolved fluorescence spectroscopy. The
      driving force of the assembly is the site selective binding of an imidazole
      connected to a free base porphyrin. Three spacers have been incorporated between
      the imidazole connector and the free base porphyrin, providing three different
      distances separating the donor and the acceptor. The high efficiencies and the
      rates of energy transfer in the set of dyads is consistent with the Forster
      energy transfer mechanism. Evidence for Forster back transfer has been obtained,
      and its efficiency and rate have been quantitatively evaluated for the first
      time.

PMID- 15738995
TI  - Modification of leaf cytology and anatomy in Brassica napus grown under above
      ambient levels of supplemental UV-B radiation.
AB  - Plants exposed to natural solar radiation usually show acclimation responses on a
      daily and seasonal basis. Many of these responses are complex and modified by
      interactions with acclimation responses to other climatic factors. While changes
      in photosynthetically active radiation (PAR, 400-700 nm) are the driving force
      for many acclimation responses in plants, radiation outside the PAR range is also
      important. Recently, interest has increased in the potential role of UV-A (320
      400 nm) and UV-B (280-320 nm) components of sunlight in plant developmental,
      physiological and daily acclimation processes. In order to explore the role of UV
      B further, Brassica napus L. cv Paroll plants were grown to maturity under 13 kJ
      d(-1) of biologically effective ultraviolet-B radiation (UV-B(BE), 280-320 nm)
      plus 800 micromol photons m(-2) s(-1) photosynthetically active radiation (PAR,
      400-700 nm) or PAR alone. Leaf anatomy and palisade cell structure were
      quantified using stereological techniques. The leaves of plants grown under UV-B
      radiation exhibited an increase in overall leaf width, although no change in leaf
      anatomy was discerned. Palisade cells in UV-B exposed leaves showed a significant
      decrease in chloroplast, mitochondrial, starch, and microbody volume density
      (Vv), while the vacuolar Vv increased compared to cells exposed to PAR only. In
      UV-B exposed leaves, there was an increase in the appressed and non-appressed
      thylakoid surface area density (Sv) within the chloroplasts. Since the relative
      proportion of appressed to non-appressed thylakoid surface area did not change,
      both thylakoid systems changed in concert with each other. Thylakoid stacks were
      broader and shorter in leaves subjected to UV-B. In general these responses were
      similar to those which occurred in plants moved from a high to low PAR
      environment and similar to mature plants exposed to 13 kJ d(-1) UV-B(BE) for only
      a short period of time. Although UV absorbing pigments increased by 21% in UV-B
      exposed leaves, there was no significant difference in chlorophyll a,b or
      carotenoid content compared to plants exposed to only PAR.

PMID- 15738997
TI  - A picosecond time-resolved study on prototropic reactions of electronically
      excited 1,5- and 1,8-diaminonaphthalenes in aqueous solution.
AB  - The proton transfer to solvent in the excited state of protonated
      diaminonaphthalenes, 1,5-diaminonaphthalene (1,5-DAN) and 1,8-diaminonaphthalene
      (1,8-DAN), in aqueous solution, has been investigated by picosecond time-resolved
      fluorescence measurements. The deprotonation rate constants of the dications of
      1,8-DAN and 1,5-DAN in the excited state to produce the corresponding monocations
      are determined to be 1.3 x 10(10) and 5.6 x 10(9) s(-1), respectively, from
      dynamic analyses of their fluorescence time profiles. The much larger proton
      dissociation rates compared with that of 1-aminonaphthalene (0.6 x 10(9) s(-1))
      can be attributed to an electron-withdrawing effect due to the ammonium group at
      the 5- or 8-position in the naphthalene ring. The remarkably large proton
      dissociation rate in 1,8-DAN can be ascribed to its larger reaction exergonicity
      which results from the electrostatic repulsion between the two ammonium groups in
      the reactant (the dication state) and the stabilization of the monocation state
      due to hydrogen bonding interactions between the NH3+ and NH2 moieties. The
      difference in their acidities in the excited state is discussed in terms of the
      reaction free energy and the proton affinities are evaluated from ab initio MO
      calculations.

PMID- 15738998
TI  - Photochemical reactions of triplet p-phenylbenzyl derivatives studied by using
      laser flash triplet-sensitization techniques.
AB  - Photochemical properties in the triplet states of p-phenylbenzyl derivatives
      (PBX; X = H, Cl, Br, OH or SH) were investigated by using laser photolysis
      techniques of triplet-acetone sensitization. Beta-bond dissociation of triplet
      phenylbenzyl mercaptan (X = SH) was shown for the first time while formation of
      triplet states were seen for phenyl toluene and phenylbenzyl alcohol by triplet
      energy transfer. Beta-bond cleavage was absent for halide compounds (X = Cl and
      Br) upon sensitization because of the short triplet lifetimes due to a heavy atom
      effect. The reactivity for beta-bond cleavage was interpreted in terms of
      difference in the bond enthalpy, D(C-X), relative to the triplet energies.

PMID- 15738999
TI  - Comparative study of the photophysical properties of indoprofen photoproducts in
      relation with their DNA photosensitizing properties.
AB  - The photophysical properties of indoprofen photoproducts have been examined in
      various solvents by absorbance and emission spectroscopies in relation with their
      photosensitizing properties. The photophysical properties of 2-[4-(1
      hydroxy)ethylphenyl]isoindolin-1-one (HOINP) and 2-(4-ethylphenyl)isoindolin-1
      one (ETINP) are typical of a singlet excited state when the ones of 2-(4
      acetylphenyl)isoindolin-1-one (KINP) are based on its triplet excited state
      according to previous work. The effect of solvent polarity on the absorption and
      fluorescence properties of HOINP and ETINP has been investigated as a function of
      Delta f, the Lippert solvent polarity parameter. A solvatochromic effect,
      function of the polarity region, has been observed for both photoproducts due to
      a change in the dipole moment of the compound upon excitation. In low-polarity
      regions, the excited state dipole moment of HOINP undergoes only a moderate
      increase (11.5 D) as compared to the dipole moment of the ground state (4.5 D)
      suggesting that the fluorescence arises from the locally excited state while in
      high-polarity regions it is strongly increased (42.9 D), which can imply that the
      emission takes place from a charge transfer state. In the case of ETINP, it would
      seem that the emitting state is rather a charge transfer state whatever the
      region is (16.9 and 31.8 D for the calculated excited-state dipole moments in the
      low and high-polarity regions, respectively). HOINP and ETINP do not produce
      thymine dimers by photosensitization but induce photooxidative damage via an
      electron transfer mechanism.

PMID- 15739000
TI  - Rufloxacin induced photosensitization in bio-models of increasing complexity.
AB  - Rufloxacin belongs to the class of fluoroquinolones that act mainly as specific
      inhibitors of bacterial Topoisomerase II. These drugs are widely known to be
      involved in various diseases ranging from cutaneous reactions to aging. The type
      II photosensitizing activity of Rufloxacin has been already demonstrated on calf
      thymus DNA and free nucleosides. The aim of this study is to examine in control
      untreated and UVA irradiated human fibroblasts the modifications on DNA status
      induced by Rufloxacin added in the culture medium. This allows to investigate the
      photosensitizing activity of Rufloxacin in a more complex cell model.
      Fibroblasts, either in the presence or in the absence of Rufloxacin, were exposed
      to UVA irradiation for different times. An experimental protocol was followed in
      order to evaluate the amount of single-strand breaks (SSB) and double-strand
      breaks (DSB) DNA fragmentation by comet assay, and plasmid photocleavage. The
      presence of oxidized bases was also evaluated using the 8-OH-dGuo test. The comet
      assay test was also employed to assess cellular repair capacity. The
      intracellular drug concentration was verified by HPLC-MS. The results confirming
      the role of Rufloxacin as photosensitizer were: (i) a time-dependent increase in
      DNA fragmentation when fibroblasts were irradiated in the presence of Rufloxacin;
      (ii) the efficiency of the cellular repair machinery to be exhaustive after 2 h
      (whereas no correlation between irradiation time and DNA damage repair was
      observed with a higher level of DNA fragmentation after shorter irradiation
      times); (iii) the increased number of cells exhibiting high DNA fragmentation,
      seen as comets with long tails, was not accompanied by a similar large extent of
      oxidised DNA base formation, as measured by 8-OH-dGuo analysis; (iv) the double
      helix SSB, formed in plasmid photosensitization, agreed with the comet assay
      results, pointing out a good correlation among the cell system and the simpler
      models used.

PMID- 15739001
TI  - True square planar [M{N(SePiPr2)2-Se,Se'}2][M = Sn, Se] complexes. An
      extraordinary geometrical arrangement for well known centers [Sn(II), Se(II)].
AB  - The syntheses and molecular structures of [M{N(SeP(i)Pr2)2-Se,Se'}2][M = Sn(2),
      Se(3)] are described, these complexes consist of discrete, monomeric molecules
      featuring MSe4 cores that comprise true square-planar geometries.

PMID- 15739002
TI  - Fluoroaryl-substituted aminoalane dimers: syntheses and structures.
AB  - Six dimeric aminoalanes of formula [Me(2)Al-mu-N(H)Ar(F)](2)(Ar(F)= 4-C(6)H(4)F
      (1), 2-C(6)H(4)F (2), 3,5-C(6)H(3)F(2)(3), 2,3,4,5-C(6)HF(4)(4), 2,3,5,6
      C(6)HF(4)(5) and C(6)F(5)(6)) have been prepared by treatment of the appropriate
      fluoroaniline with AlMe(3) in toluene solution at 25 degrees C. The structures of
      1-6 were determined by X-ray crystallography.

PMID- 15739004
TI  - The oxidation of water by cerium(IV) catalysed by nanoparticulate RuO2 on
      mesoporous silica.
AB  - Mesoporous silicates are prepared by templating on the hexagonal (H1) mesophase
      of surfactant bipyridine complexes of ruthenium(II) using a true liquid-crystal
      templating approach. On calcination, the surfactant template is removed except
      for the central metal ion that is oxidised, forming nanoparticles of RuO2 that
      deposit within the pores. RuO2 is a known oxidation catalyst and, despite its
      anhydrous nature in these silicates, is found to be very active in catalyzing the
      oxidation of water by acidic CeIV.

PMID- 15739003
TI  - Inhibition of Thermus thermophilus HB8 thioredoxin activity by platinum(II).
AB  - A 1:1 thioredoxin-Pt(bpy) complex was prepared by adding [Pt(bpy)(en)]Cl(2)(bpy =
      2,2'-bipyridine, en = ethylenediamine) to Thermus thermophilus HB8 thioredoxin in
      pH 8 phosphate buffer. Matrix-assisted laser desorption-ionization time of flight
      mass spectrometry (MALDI-TOF MS) and UV spectra of indicate the formation of
      Pt(bpy)(cys-Ala-Pro-cys-containing peptide fragment). These findings suggest that
      the Pt(bpy)(2+) unit binds to the active site of thioredoxin. The thioredoxin
      platinum complex has no catalytic activity for the reduction of glutathione
      disulfide in the presence of NADPH and thioredoxin reductase, so that the
      platinum complex functions as an inhibitor.

PMID- 15739005
TI  - Ligand exchange upon oxidation of a dinuclear Mn complex--detection of structural
      changes by FT-IR spectroscopy and ESI-MS.
AB  - The structural rearrangements triggered by oxidation of the dinuclear Mn complex
      [Mn(2)(bpmp)(mu-OAc)2]+(bpmp = 2,6-bis[bis(2-pyridylmethyl)amino]methyl-4
      methylphenol anion) in the presence of water have been studied by combinations of
      electrochemistry with IR spectroscopy and with electrospray ionization mass
      spectrometry (ESI-MS). The exchange of acetate bridges for water (D2O) derived
      ligands in different oxidation states could be monitored by mid-IR spectroscopy
      in CD(3)CN-D(2)O mixtures following the v(as(C-O)) bands of bound acetate at
      1594.4 cm(-1)(II,II), 1592.0 cm(-1)(II,III) and 1586.5 cm(-1)(III,III).
      Substantial loss of bound acetate occurs at much lower water content (< 0.5% v/v)
      in the III,III state than in the II,II and II,III states (> or = 10%). The ligand
      exchange reactions do not initially reduce the overall charge of the complex but
      facilitate further oxidation by proton-coupled electron transfer as the water
      derived ligands are increasingly deprotonated in higher oxidation states. In the
      IR spectra deprotonation could be followed by the formation of acetic acid (DOAc,
      approximately 1725 cm(-1), v(C-O)) from the released acetate (1573.6 cm(-1),
      v(as(C-O))). By the on-line combination of an electrochemical flow cell with ESI
      MS several product complexes could be identified. A di-mu-oxo bridged III,IV
      dimer [Mn(2)(bpmp)(mu-O)(2)](2+)(m/z 335.8) can be generated at potentials below
      the III,III/II,III couple of the di-mu-acetato complex (0.61 V vs. ferrocene).
      The ligand-exchange reactions allow for three metal-centered oxidation steps to
      occur from II,II to III,IV in a potential range of only 0.5 V, explaining the
      formation of a spin-coupled III,IV dimer by photo-oxidation with [Ru[bpy)(3)](3+)
      in previous EPR studies.

PMID- 15739006
TI  - A spectroscopic and computational study on the effects of methyl and phenyl
      substituted phenanthroline ligands on the electronic structure of Re(I)
      tricarbonyl complexes containing 2,6-dimethylphenylisocyanide.
AB  - [Re(CO)3(CNx)(L)]+, where CNx = 2,6-dimethylphenylisocyanide, forms complexes
      with L = 1,10-phenanthroline (1), 4-methyl-1,10-phenanthroline (2), 4,7-dimethyl
      1,10-phenanthroline (3), 3,4,7,8-tetramethyl-1,10-phenanthroline (4), 2,9
      dimethyl-1,10-phenanthroline (5) and 2,9-dimethyl-4,7-diphenyl-1,10
      phenanthroline (6). The metal-ligand-to-ligand charge transfer transition (MLLCT)
      absorption bands follow the series: (27800 cm(-1)) > 1, 2, 4 and 5(27500 cm(-1))
      > 6 (26600 cm(-1)). Density functional theory (DFT) geometry optimizations reveal
      elongated Re-N (L) distances of 2.28 and 2.27 A for 5 and 6, respectively,
      compared to 2.23 A for 1-4. The reversible reduction potentials (E(1/2(red))) of
      1-4 are linearly dependent on the B3LYP calculated LUMO energies. Time-dependent
      (TD) DFT and conductor-like polarizable continuum model (CPCM) calculated singlet
      excited states deviate by 700 cm(-1) or less from the experimental absorption
      maxima and aid in the spectral assignments. The (3)MLLCT emitting state energies
      are within 900 cm(-1) of the experimental 77 K emission energies for 1-6. The 77
      K emission energies, E(1/2(red)), and the room temperature emission quantum
      yields (phi(LUMO)(em)) decrease in the order 1 >2 >3 >4 whereas E(LUMO) and the
      room temperature emission energies follow the opposite trend. The emission
      lifetimes (tau(em)) decrease in the order 3 > 4 >2 >1 >5 with 3 having the
      highest emission lifetime values of 26.9 micros at room temperature and 384
      micros at 77 K and complex 5 having the lowest emission lifetimes of 4.6 micros
      at room temperature and 61 micros and 77 K.

PMID- 15739007
TI  - Vibrational and electronic structure of the dinuclear bis(mu-nitrido) vanadium(v)
      complex [V(N{N"}2)(mu-N)]2: spectroscopic properties of the M2(mu-N)2 diamond
      core.
AB  - The vibrational and electronic structure of the bis(mu-nitrido) bridged complex
      [V(N{N"}2)(mu-N)]2 (1) (where [N{N"}2](2-)=[(Me3Si)N{CH(2)CH(2)N(SiMe3)}2](2-))
      is analyzed. Assignment of the five modes of the V(2)(mu-N)2 core is based on
      (15)N isotope shifts and a DFT calculation on the calculated structure I which is
      an exact reproduction of 1. The three Raman active modes of the planar V(2)(mu
      N)2 core are found in the Raman spectrum whereas the two IR allowed vibrations
      are identified in the infrared spectrum. Furthermore, the electronic structure of
      is described which complements earlier theoretical studies on the reaction
      pathway leading to 1(V. M. E. Bates, G. K. B. Clentsmith, F. G. N. Cloke, J. C.
      Green, H. D. L. Jenkin, Chem. Commun., 2000, 927). Based on the MO scheme of I
      the UV-vis transitions of 1 are assigned.

PMID- 15739008
TI  - Kinetics of formation and dissociation of lanthanide(III) complexes with the 13
      membered macrocyclic ligand TRITA4-.
AB  - The tetraazamacrocyclic ligand TRITA(4-) is intermediate in size between the
      widely studied and medically used 12-membered DOTA(4-) and the 14-membered TETA(4
      ). The kinetic inertness of GdTRITA(-) was characterized by the rates of exchange
      reactions with Zn(2+) and Eu(3+). In the Zn(2+) exchange, a second order [H(+)]
      dependence was found for the pseudo-first-order rate constant (k(0)=(4.2 +/- 0.5)
      x 10(-7) s(-1); k'=(3.5 +/- 0.3) x 10(-1) M(-1)s(-1), k" =(1.4 +/- 0.4) x 10(3)
      M(-2)s(-1)). In the Eu(3+) exchange, at pH <5 the rate decreases with increasing
      concentration of the exchanging ion, which can be accounted for by the
      transitional formation of dinuclear GdTRITAEu(2+) species. At physiological pH,
      the kinetic inertness of GdTRITA(-) is considerably lower than that of GdDOTA(
      )(t(1/2)= 444 h (25 degrees C) vs. 3.8 x 10(5) h (37 degrees C), respectively).
      However, GdTRITA(-) is still kinetically more inert than GdDTPA(2-), the most
      commonly used MRI contrast agent (t(1/2)= 127 h). The formation reactions of
      LnTRITA(-) complexes (Ln = Ce, Gd and Yb) proceed via the rapid formation of a
      diprotonated intermediate and its subsequent deprotonation and rearrangement in a
      slow, OH(-) catalyzed process. The stability of the LnH(2)TRITA* intermediates
      (log K(LnH2L*)= 3.1-3.9) is lower than that of the DOTA-analogues. The rate
      constants of the OH(-) catalyzed step increase with decreasing lanthanide ion
      size, and are about twice as high as for DOTA-complexes.

PMID- 15739010
TI  - Phenylphosphatrioxa-adamantanes: bulky, robust, electron-poor ligands that give
      very efficient rhodium(I) hydroformylation catalysts.
AB  - The cage phosphines 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane
      (1a) and 1,3,5,7-tetraethyl-6-phenyl-2,4,8,trioxa-6-phosphaadamantane (1b) have
      been made by the acid catalysed addition of PhPH(2) to the appropriate beta
      diketones; the acid used (HCl, H(3)PO(4) or H(2)SO(4)) and its concentration
      affect the rate and selectivity of these condensation reactions. Phosphines 1a
      and 1b react with [PdCl(2)(NCPh)(2)] to form complexes trans-[PdCl(2)(1a)(2)](2a)
      and trans-[PdCl(2)(1b)(2)](2b) as mixtures of rac and meso diastereoisomers. The
      platinum(II) chemistry is more complicated and when 1a or 1b is added to
      [PtCl(2)(cod)], equilibrium mixtures of trans-[PtCl(2)L(2)] and
      [Pt(2)Cl(4)L(2)](L = or ) are formed in CH(2)Cl(2) solution. Meso/rac mixtures of
      trans-[MCl(CO)(1a)(2)] M = Ir (6a) or Rh (7a) are formed upon treatment of
      MCl(3).nH(2)O with an excess of 1a and the anionic cobalt complex
      [NHEt(3)][CoCl(3)(1a)](9) was isolated from the product formed by CoCl(2).6H(2)O
      and 1a. The nu(CO) values from the IR spectra of 6a and 7a suggest that 1a
      resembles a phosphonite in its bonding to Rh and Ir. Crystal structures of meso
      2a, meso-2b, rac-6a and 9 are reported and in each case a small intracage C-P-C
      angle of ca. 94 degrees is observed; this may partly explain the bonding
      characteristics of ligands 1a and 1b. The cone angles for 1a and 1b are similar
      and large (ca. 200 degrees). Rhodium complexes of ligands 1a and 1b are
      hydroformylation catalysts with similarly high activity to catalysts derived from
      phosphites. The catalysts derived from 1a and 1b gave unusually low linear
      selectivity in the hydroformylation of hexenes. This feature has been further
      exploited in quaternary-selective hydroformylations of unsaturated esters;
      catalysts derived from 1a give better yields and regioselectivities than any
      previously reported catalyst.

PMID- 15739009
TI  - Syntheses, structural analyses and redox kinetics of four-coordinate [CuL2]2+ and
      five-coordinate [CuL2(solvent)]2+ complexes (L = 6,6'-dimethyl-2,2'-bipyridine or
      2,9-dimethyl-1,10-phenanthroline): completely gated reduction reaction of
      [Cu(dmp)2]2+ in nitromethane.
AB  - [Cu(2,9-dimethyl-1,10-phenanthroline)(2)](2+) and [Cu(6,6'-dimethyl-2,2'
      bipyridine)(2)](2+/+) complexes with no coordinated solvent molecule were
      synthesized and the crystal structures were analyzed: the coordination geometry
      around the Cu(i) center was in the D(2d) symmetry while a D(2) structure was
      observed for the four-coordinate Cu(ii) complexes. Coordination of a water or an
      acetonitrile molecule was found in the trigonal plane of the five-coordinate
      Cu(ii) complex in the Tbp(trigonal bipyramidal) structure. Spectrophotometric
      analyses revealed that the D(2) structure of the Cu(ii) complex was retained in
      nitromethane, although a five-coordinate Tbp species (green in color), was
      readily formed upon dissolution of the solid (reddish brown) in acetonitrile. The
      electron self-exchange reaction between D(2d)-Cu(I) and D(2)-Cu(II), observed by
      the NMR method, was very rapid with k(ex)=(1.1 +/- 0.2) x 10(5) kg mol(-1) s(-1)
      at 25 degrees C (DeltaH*= 15.6 +/- 1.3 kJ mol(-1) and DeltaS*=-96 +/- 4 J mol(-1)
      K(-1)), which was more than 10 times larger than that reported for the self
      exchange reaction between D(2d)-Cu(I) and Tbp-Cu(II) in acetonitrile. The cross
      reduction reactions of D(2)-Cu(ii) by ferrocene and decamethylferrocene in
      nitromethane exhibited a completely gated behavior, while the oxidation reaction
      of D(2d)-Cu(i) by [Ni(1,4,7-triazacyclononane)(2)](3+) in nitromethane estimated
      an identically large self-exchange rate constant to that directly obtained by the
      NMR method. The electron self-exchange rate constant estimated from the oxidation
      cross reaction in 50% v/v acetonitrile-nitromethane mixture was 10 times smaller
      than that observed in pure nitromethane. On the basis of the Principle of the
      Least Motion (PLM) and the Symmetry Rules, it was concluded that gated behaviors
      observed for the reduction reactions of the five-coordinate Cu(ii)-polypyridine
      complexes are related to the high-energy C(2v)--> D(2d) conformational change
      around Cu(ii), and that the electron self-exchange reactions of the Cu(ii)/(i)
      couples are always adiabatic through the C(2v) structures for both Cu(ii) and
      Cu(i) since the conformational changes between D(2d), D(2) and C(2v) structures
      for Cu(i) as well as the conformational change between Tbp and C(2v) structures
      for Cu(ii) are symmetry-allowed. The completely gated behavior observed for the
      reduction reactions of D(2)-Cu(ii) species in nitromethane was attributed to the
      very slow conformational change from the ground-state D(2) to the entatic D(2d)
      structure that is symmetry-forbidden for d(9) metal complexes: the very slow back
      reaction, the forbidden conformational change from entatic D(2d) to the ground
      state D(2) structure, ensures that the rate of the reduction reaction is
      independent of the concentration of the reducing reagent.

PMID- 15739011
TI  - Mechanism of formation of iron(II) complexes with pentadentate ligands via C-C
      bond formation between trans-[Fe(2,4-bis(2
      pyridylmethylimino)pentane)(MeCN)2]ClO4]2.MeCN and various nitriles.
AB  - The order of relative reactivity of nitriles for the formation of Fe(II)
      complexes (2s) with 3-(1-alkyl(or aryl)methyl)-1-imino-2,4-bis(2
      pyridylmethylimine)(L(2)s) from that with 2,4-bis(2-pyridylmethylimono)pentane
      (L1), trans-[FeL(1)(MeCN)(2)][ClO(4)](2).MeCN (1), and various nitriles has been
      determined based on the following order: C(6)F(5)CN > 3,4-difluorobenzonitrile >
      4-fluorobenzonitrile > C(6)H(5)CN > C(6)H(5)CH(2)CN > C(2)H(5)CN > MeCN >
      Me(2)CHCN >>Me(3)CN. An iron(II) complex with L1 in a cis-configuration was
      prepared as the ternary complex [FeL(1)(bpy)][ClO(4)](2).1.5MeNO(2).0.5H(2)O, 3a
      (bpy = bipyridine). Compounds 2s and 3a undergo enantiomeric interconversion with
      an activation energy of ca. 60 kJ mol(-1).

PMID- 15739012
TI  - Influence of geometry on reductive elimination of hydrocarbyl-palladium-carbene
      complexes.
AB  - The influence of spectator ligand bite angle and the twist angle of the carbene
      on the reductive elimination of N-heterocyclic carbenes (NHCs) from palladium bis
      phosphine complexes has been investigated using density functional theory. The
      spectator bite angle was found to have a significant influence on both the
      activation energy (E(act)) and the enthalpy of reaction. Widening of the bite
      angle was found to lower E(act) and increase the enthalpy of reaction. In
      contrast, rotation of the carbene with respect to the PdL(2) plane was found to
      have little influence on E(act). At carbene twist angles approaching 0 degrees
      however, relief of the increased steric strain provides a considerable driving
      force for the decomposition reaction.

PMID- 15739014
TI  - Rhodium hydride formation in the presence of a bulky monophosphite ligand: a
      spectroscopic and solid-state investigation.
AB  - A study has been carried out on rhodium catalyst preforming when modified with
      the bulky tris(2,4-di-tert-butylphenyl) phosphite, P(Obtbp)(3). X-Ray crystal
      structure determinations of a tropolone-type precursor complex
      [Rh(TropBr(3))(CO){P(Obtbp)(3)}].P(Obtbp)(3).CH(3)COCH(3)(TropBr(3)= 3,5,7
      tribromotropolonate) and the free P(Obtbp)(3) ligand are reported. Systematic in
      situ IR and NMR studies of the particular rhodium phosphite modified catalyst and
      its precursors have led to the identification of two distinct rhodium hydride
      species. A {(1)H,(31)P} HMBC NMR experiment afforded clarity on the (31)P NMR
      spectra observed under hydroformylation conditions. The species were identified
      as [HRh(CO)(3){P(Obtbp)(3)}] and [HRh(CO)(2){P(Obtbp)(3)}(2)]. Attention was also
      given to the rate of catalyst formation when starting from different rhodium
      precursors.

PMID- 15739013
TI  - DNA damage induced by sulfite autoxidation catalyzed by copper(II) tetraglycine
      complexes.
AB  - Copper(II)/(III) tetraglycine complexes were investigated for their ability to
      catalyze the autoxidation of sulfite resulting in oxidative DNA damage. The focus
      of this work is on DNA damage by Cu(III) and oxysulfur radicals formed by the
      oxidation of S(IV) oxides by dissolved oxygen in the presence of Cu(II)
      tetraglycine complexes. The results suggest that sulfite is rapidly oxidized by
      oxygen in the presence of Cu(II) complexes producing Cu(III) tetraglycine, which
      can be monitored spectrophotometrically at 365 nm. A synergistic effect of Cu(II)
      with a second metal ion (Ni(II), Co(II) or Mn(II) traces) was observed.

PMID- 15739015
TI  - Kinetics and mechanism of the Co(II)-assisted oxidation of thioureas by dioxygen.
AB  - Catalytic oxidation of N,N'-dimethylthiourea and thiourea by dioxygen in water
      using a new cobalt(II) complex of octasulfophenyltetrapyrazinoporphyrazine was
      performed under mild conditions. The reaction is shown to include the formation
      of an intermediate anionic five-coordinate complex followed by an unusual two
      electron oxidation to produce the corresponding urea and elemental sulfur (S8).
      Kinetic and thermodynamic parameters for the different reaction steps of the
      process were determined. Drastic differences in catalytic activity of cobalt and
      iron octasulfophenyltetrapyrazinoporphyrazines were observed.

PMID- 15739016
TI  - Photophysical study of a family of [Ru(phen)2(Me n dpq)]2+ complexes in different
      solvents and DNA: a specific water effect promoted by methyl substitution.
AB  - The synthesis and spectroscopic characterisation of a family of ruthenium
      complexes [Ru(phen)(2)(Me(n)dpq)](2+)(n= 0, 1, 2) are reported and the
      photophysical effect of the progressive methyl substitution on the dpq ligand
      ascertained in a range of solvents and in the presence of DNA:
      [Ru(phen)(2)(dpq)](2+)(1), [Ru(phen)(2)(Medpq)](2+)(2) and
      [Ru(phen)(2)(Me(2)dpq)](2+)(3)(where dpq is dipyrido[3,2-f:2',3'-h]-quinoxaline;
      Medpq is 2-methyldipyrido[3,2-f:2',3'-h]-quinoxaline; Me(2)dpq is 2,3
      dimethyldipyrido[3,2-f:2',3'-h]-quinoxaline and phen is 1,10-phenanthroline). The
      increase in electron density following substitution renders the quinoxaline
      nitrogen atoms more basic in the ground state to yield pK(a) values of -1.9, 
      2.3, and -2.7 for 3, 2, and 1, respectively. The methyl groups have a pronounced
      effect on the excited state photophysics of 1-3. In organic solvents, the non
      radiative decay constant correlates well with the solvent polarity parameter pi*,
      with the effect being more pronounced with increasing methyl substitution. On the
      contrary, in aqueous solution there is a ca. four-fold decrease in the non
      radiative decay constant upon methyl substitution. This "specific water effect"
      may be explained in terms of deactivation of the excited state by hydrogen
      bonding interactions between water and the quinoxaline nitrogen atoms, which is
      reduced on moving from 1 to 3. The excited state lifetimes and luminescence
      intensities for substantially increase when bound to DNA in aerated aqueous
      solutions, with a six-fold increase, compared to a more moderate three-fold
      increase for 2 and 3.

PMID- 15739017
TI  - The effect of pyridinecarboxylate chelating groups on the stability and
      electronic relaxation of gadolinium complexes.
AB  - The ligand N,N'-bis[(6-carboxy-2-pyridylmethyl]ethylenediamine-N,N'-diacetic acid
      (H(4)bpeda) was synthesised using an improved procedure which requires a reduced
      number of steps and leads to a higher yield with respect to the published
      procedure. It was obtained in three steps from diethylpyridine-2,6-dicarboxylate
      and commercially available ethylenediamine-N,N[prime or minute]-diacetic acid
      with a total yield of approximately 20%. The crystal structure of the hexa
      protonated form of the ligand which was determined by X-ray diffraction shows
      that the four carboxylates and the two amines are protonated. The crystal
      structure of the polynuclear complex
      [Gd(bpeda)(H(2)O)(2)](3)[Gd(H(2)O)(6)](2)Cl(3)(2), isolated by slow evaporation
      of a 1:1 mixture of GdCl(3) and H(4)bpeda at pH approximately 1, was determined
      by X-ray diffraction. In complex three [Gd(bpeda)(H(2)O)(2)] units, containing a
      Gd(III) ion ten-coordinated by the octadentate bpeda and two water molecules, are
      connected in a pentametallic structure by two hexa-aquo Gd(3+) cations through
      four carboxylato bridges. The protonation constants (pK(a1)= 2.9(1), pK(a2)=
      3.5(1), pK(a3)= 5.2(2), and pK(a4)= 8.5(1)) and the stability constants of the
      complexes formed between Gd(III) and Ca(II) ions and H(4)bpeda (log beta(GdL)=
      15.1(3); log beta(CaL)= 9.4(1)) were determined by potentiometric titration. The
      unexpected decrease in the stability of the gadolinium complex and of the calcium
      complex of the octadentate ligand bpeda(4-) with respect to the hexadentate
      ligand edta(4-) has been interpreted in terms of an overall lower contribution to
      stability of the metal-nitrogen interactions. The EPR spectra display very broad
      lines (apparent DeltaH(pp) approximately 800-1200 G at X-band and 90-110 G at Q
      band depending on the temperature), indicating a rapid transverse electron spin
      relaxation. At X-band, Gd(bpeda) is among the fastest relaxing Gd(3+) complexes
      to date suggesting that the presence of pyridinecarboxylate chelating groups in
      itself does not lead to slow electron relaxation.

PMID- 15739018
TI  - Formation and dissociation kinetics of Cu(II) and Ni(II) complexes with N2S2
      macrocycles.
AB  - The kinetics of the formation and dissociation of the Cu(2+) and Ni(2+) complexes
      with a series of N(2)S(2) macrocycles, in which the ring size and the geometry of
      the arrangement of the donor groups have been varied, have been measured at 25
      [degree]C and I= 0.5 (KNO(3)). Both the deprotonated (L) and the monoprotonated
      (LH(+)) form of the ligands are reactive species in the formation step. In their
      deprotonated form, first bond formation, in some cases supported by an ICB
      effect, is rate determining, independently of the ring size. In the
      monoprotonated form, we find slower rates, due to the charge repulsion and/or
      conformation changes induced by hydrogen bonds. In contrast the mechanism of the
      dissociation is very dependent on the ring size. The complexes with the smaller
      rings react as flexible open-chain ligands directly with H(+). In contrast, the
      complexes with the larger rings react in a similar way as rigid ligands: first
      the metal amine bond slowly dissociates so that the free electron pair of the
      amine can take the "out conformation" and then it is protonated. The 14-membered
      macrocycle L(3) forms complexes in which the metal ions are ideally coordinated
      so that their dissociation becomes extremely slow.

PMID- 15739019
TI  - Prognostic and predictive value of cathepsins D and L in operable breast cancer
      patients.
AB  - None of the established prognostic factors in breast cancer (BC) is able to
      determine the final outcome with certainity. Tumor biological factors involved in
      tumor invasion and metastasis, such as cathepsins and proteins of u-PA system,
      have been put forward in the recent literature as strong novel prognostic factors
      in BC. We therefore evaluated prognostic and predictive value of cathepsin-D (CD)
      and cathepsin-L (CL) in 715 operable BC patients. CD and CL were determined in
      tumor extracts using immunoradiometric and ELISA assays, respectively. During
      follow-up (median 37 months), 151 (21%) patients relapsed. In a multivariate
      analysis of disease-free survival (DFS), CL (p=0.04), nodal status (p<0.001) and
      hormone receptor status (p<0.001) were the only independent significant
      prognostic factors. CL thus provided independent prognostic information on DFS
      and could also predict a response to adjuvant chemotherapy (ChT), while CD had no
      significant prognostic and predictive impact.

PMID- 15739020
TI  - A new look at the prognostic value of the estrogen, progesterone and epidermal
      growth factor receptors in breast cancer tissue.
AB  - The aim of the study was to evaluate the influence of the receptor status of
      primary breast cancer and of a number of selected clinical and morphological
      patient characteristics. The receptors were determined by biochemical
      radiocompetitive methods. Disease free survival (DFS) and overall survival (OS)
      were determined by Cox proportional hazard model. The influence of ER, PR, and
      EGFR on patient survival was analyzed in two ways: 1) as a separate parameter of
      each receptor and 2) as a common parameter consisting of 8 variables of
      concomitant presence or absence of the receptors. The first set of analyses had
      shown that EGFR as an independent parameter had no prognostic value either for
      DFS or OS because of a lack of statistical significance. Higher ER concentrations
      were positive and lower concentrations were negative prognostic factors, but only
      for DFS. PR was always a positive prognostic factor for DFS and OS and its
      prognostic value increased with concentration increase. In the second analysis it
      was found that patients with receptor status ER+PR+EGFR+; ER-PR+EGFR-; ER+PR+EGFR
      ; and ER-PR-EGFR- were having better parameters of DFS and OS (relative risks for
      DFS or OS were between 0.22-1.16). The patients with receptor status: ER
      PR+EGFR+; ER+PR-EGFR-, ER-PR-EGFR+ and ER+PR-EGFR+ exhibited a more aggressive
      disease course (relative risks for DFS and OS were between 1.46-3.95). Moreover,
      it was found that tumor size, nodal status and patient age were independent
      prognostic factors for DFS and OS of patients.

PMID- 15739021
TI  - An antigen recognized on cells in apoptosis detected by monoclonal antibody 2E12.
AB  - Monoclonal antibody 2E12 was prepared by immunization of mice with cells of a
      chronic myeloid leukemia cell line MOLM-7. Human hematopoietic cell lines JURKAT,
      HPB-ALL, RC2A and MOLM-7 were induced to receptor mediated apoptosis by the
      treatment with anti-Fas monoclonal antibody 7C11 and subsequently tested for
      reactivity with 2E12 antibody in comparison to staining with annexin V-FITC and
      PI in the two-color immunofluorescence and flow cytometry. After 2, 5, 24, and 48
      hours of induction, a gradual increase of the percentage of 2E12 positive cells
      in all cell lines was observed, which partially correlated with an increase of
      annexin V-FITC binding with a delay of about 12 hours. In the two- color
      fluorescence microscopy the 2E12 antibody positivity was restricted to the
      annexin V positive cells, but their number was lower. The binding of 2E12 did not
      induce apoptosis nor influenced the binding of annexin V. We suppose that the
      antibody 2E12 detects an antigen expressed on a subpopulation of cells in death.
      Therefore it can be useful as a new marker for further dissection between living,
      apoptotic and necrotic cellular populations in vitro.

PMID- 15739022
TI  - TNF-alpha induced changes in cell membrane antigen expression on K-562 cells
      associated with increased lactate dehydrogenase (LDH) release.
AB  - TNF-alpha is a pleiotropic cytokine, which induces death of sensitive cells,
      whose effect depend on cell membrane receptor expression, cell cycle phases, as
      well as on intracellular ratio of pro- apoptotic and anti-apoptotic molecule
      expression. Since determination of LDH release from cultured cells in vitro,
      reflects early membrane alterations, we estimated and compared LDH release from
      cultured cells with changes in cell membrane antigen expression on K-562 cells
      after TNF-alpha treatment by flow cytometry. The significant increase in LDH
      release activity and cytotoxicity values was associated with decrease in membrane
      molecule expression for CD45 and CD30 as well as for low expressed CD45RA and
      CD38 after TNF-alpha treatment. However, percentage of decrease of all examined
      molecules is not uniform, and appears to depend on the respective level of pre
      treatment values expression and molecule type. These results indicated the
      complexity of events on cell membrane, including association between increasing
      LDH release and decrease of antigen expression of membrane molecules following
      TNF-alpha mediated processes.

PMID- 15739023
TI  - The role of anti-CENP-B and anti-SS-B antibodies in breast cancer.
AB  - A close relationship between autoimmunity and malignant diseases has been
      supposed for a long time. In clinical practice, anti-SS-B and anti-CENP-B
      antibodies are used as serologic markers for autoimmune diseases. In this study,
      anti-SS-B and anti-CENP-B autoantibodies were studied in breast cancer patients
      and compared to a control group surgically treated due to benign diseases. These
      antibodies were evaluated by enzyme linked immunoassay and serum values >10 U/ml
      were accepted as positive. Fifty-five patients with breast cancer and 25 patients
      with benign diseases were prospectively included in the study. In the breast
      cancer group, both anti-CENP-B (33% vs. 8%) and anti-SS-B (44% vs. 24%)
      autoantibodies had higher positivity compared to the control group, but this
      difference reached statistical significance only for anti-CENP-B antibodies
      (p=0.02). Besides, anti-SS-B positivity was detected more frequently in breast
      cancer patients with axillary involvement (63% vs. 24%) (p=0.006) and increased
      as the number of involved lymph nodes increased in the axilla (p=0.03). Although
      the clinical significance of autoantibody detection in cancer patients is still
      not clear, autoantibodies especially detected in individuals without proven
      autoimmune diseases needs to be thoroughly evaluated for early diagnosis and
      treatment of various cancers.

PMID- 15739024
TI  - Application of flow cytometry immunophenotyping and multidrug resistance assay in
      B-cell acute lymphoid leukemia and multiple myeloma.
AB  - Multidrug resistance is one of the mechanisms how to explain failure of
      chemotherapy in patients with different hematological malignancies. In this study
      we aimed to evaluate and compare the drug resistance in B-cell acute lymphoid
      leukemia (B-ALL) and multiple myeloma (MM) in association with their
      immunophenotypes and genotypes. Eleven patients with B-ALL and 14 patients with
      MM were classified according to prognostic factors. Standard MoAb panel for ALL
      and triple labeled antibodies (CD38/CD56/CD19) and detection of intracellular
      light chains for MM were used. Flow cytometric calcein assay was performed for
      measure of P- glycoprotein (MDR-1) and multidrug resistance associated protein
      (MRP-1) activity. Markers CD19, CD20 and HLA-DR proved to be useful in
      identifying cells of B-lymphoid lineage. CD34 progenitor cell antigen was present
      in high proportion of ALL blasts. Both the abnormal plasmacell populations and
      their monoclonality in MM were confirmed by immunophenotyping, too. The mean MDR
      activity factor (MAF) values were not different in patients with MM and B- ALL.
      However, the mean MRP-1 values in MM were significantly lower than MAF-MDR-1
      (1.85+/-3.8 versus 5.92+/-7.45, p=0.05), but we have found lower values in
      refractory conditions as expected from previous studies of acute myeloid
      leukemia. The immunophenotyping was helpful in detection of abnormal populations
      showing no correlation with the MDR. However, in this study we could not confirm
      high MDR activity despite of the failure of chemotherapy. The calcein assay seems
      to be useful for quantitative and sensitive measurement of the MDR proteins. The
      low activity of MDR- 1 and MRP-1 in MM need further clarification, indicating the
      involvement of different transport in the resistance mechanism.

PMID- 15739025
TI  - Comparison of the serum erythropoietin levels in chemotherapy-naive and cisplatin
      treated cancer patients.
AB  - There are conflicting data about the effects of cisplatin on erythropoietin (EPO)
      response to anemia. Aim of our study was to investigate whether endogenous EPO
      response to anemia in cisplatin treated patients was insufficient in comparison
      to the anemic chemotherapy-naive cancer patients and non cancer patients with
      iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110
      g/l were included in the study. Fifteen chemotherapy- naive cancer patients were
      enrolled in Group A. Group B consisted of 15 patients who had been treated with
      three cycles of cisplatin chemotherapy and then became anemic and in Group C were
      included 15 patients who had iron deficiency anemia, without any malignancy. The
      mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/
      2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively).
      However, EPO levels were found to be significantly lower in Group A and Group B
      than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml,
      respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No
      significant difference was found between Group A and B (p=0.917). Opposite the
      iron deficiency anemia, cancer anemia is associated with an inadequate EPO
      response to anemia and administration of cisplatin does not lead to it further
      deterioration.

PMID- 15739026
TI  - Effect of doxorubicin on actin reorganization in Chinese hamster ovary cells.
AB  - Exposure of Chinese hamster ovary (CHO AA8) cells to doxorubicin in doses of 75
      microM resulted in reorganization of F-actin filaments and characteristic feature
      of apoptosis. Even increase in size of CHOAA8 cells was observed. Attached cells
      become more flattered and elongated than control ones. Intense labeling of F
      actin around the nucleus and disrupted filaments in cytoplasm as well as stress
      fibres and bundles of F-actin were seen. Cells detached were rather rounded and
      there were not stress fibres present. In these cells the network of F-actin was
      weak and rather disrupted and cells with buds labelled for F-actin were observed.
      In section from confocal microscopy labeling of F-actin in nucleus was confirmed.
      Electron microscopy showed cells with multisegmented nuclei. Cells with
      intracellular area with small and large vacuoles and containing also electron
      dense material were seen. Other cellular organelles were rather well preserve.
      There were margination and condensation of chromatin in nucleus. Immunogold
      labelling of actin was observed in cells whether or not treated with doxorubicin.
      Positivity for actin was localized in the nuclei and cytoplasm. In the nucleus
      gold particles were localized predominantly in the area of condense chromatin.
      Positive labeling for actin was not found after control incubation. These
      findings show that doxorubicin promotes changes in the distribution of actin in
      CHOAA8 cells and that reorganization of actin in these cells is involved in
      process of apoptosis.

PMID- 15739027
TI  - No evidence of HTLV-I infection in patients with mycosis fungoides and Sezary
      syndrome.
AB  - The involvement of human T-cell lymphotropic virus type I (HTLV-I) in the
      etiology of cutaneous T-cell lymphomas (CTCL) is still controversial. The aim of
      the study was to evaluate the role of HTLV-I in the pathogenesis of mycosis
      fungoides (MF) and Sezary syndrome (SS) in Polish patients. The studied group
      consisted of 42 patients with MF, 5 with SS and 25 with chronic dermatitis. DNA
      was extracted from snap-frozen and paraffin-embedded skin biopsies and from
      peripheral blood. Polymerase chain reaction (PCR or nested PCR) was carried out
      for amplification of different regions of HTLV-I genome. Primer sets flanking pX,
      p 19, U5, tax and pol genes were used in the investigation. The presence of HTLV
      I antibody was examined in 46 sera samples with the use of anti-HTLV-I/II EIA
      test. HTLV-I antibodies were not detected in any collected sera samples. PCR with
      two primer sets homologous to the pX region of HTLV-I showed negative results in
      all samples investigated. To confirm these results two other primer pairs
      specific for U5 and gag regions were designed. With these primer pairs no PCR
      product, except that in positive control, was observed. For more sensitive
      amplification a nested-PCR with pol and tax specific primers was performed. HTLV
      I probably does not play an important role in the pathogenesis of MF in Polish
      patients.

PMID- 15739028
TI  - Prediction of radiation pneumonitis: dose-volume histogram analysis in 62
      patients with non-small cell lung cancer after three-dimensional conformal
      radiotherapy.
AB  - The purpose of the study was to determine the relation between the incidence of
      radiation pneumonitis (RP) and available parameters from a dose-volume histogram
      (DVH) in patients with non-small cell lung cancer (NSCLC) who underwent three
      dimensional conformal radiotherapy treatment. Between January 1999 and August
      2003 in the Greatpoland Cancer Center, 62 patients with NSCLC were treated using
      three-dimensional conformal radiotherapy (3D CRT). All patients were treated 5
      days per week with daily fractionation of 2 Gy to total dose of 60 Gy. All
      patients were available for analysis for symptomatic RP. Radiation pneumonitis
      was graded according to the RTOG/EORTC morbidity scoring classification. Logistic
      regression analysis was performed to test the association between RP and the
      following DVH parameters: mean lung dose (MLD), volume of lung receiving > or =20
      Gy (V20 ) and > or =30 Gy (V30) and normal tissue complication probability
      (NTCP). Additionally, correlation of the following clinical factors such as: age,
      sex, tumor site, performance status (KPS), and additional therapy (chemotherapy)
      with incidence of the RP were performed. Moreover, correlation between DVH
      parameters were tested using Spearman method. Thirty out of 62 patients (48%)
      developed RP grade 0 or 1 (0 grade -- 12%, 1 grade -- 36%) and 32 (52%) grade 2
      or 3 (2 grade -- 47%, 3 grade -- 5%). In the logistic regression analysis, all
      DVH parameters were associated with RP (p in range from 0.004 to 0.007). The
      strongest association was observed for NTCP and V30 (p=0.004). On the other hand,
      a weak association was found for V20 (p=0.007). The correlations between all DVH
      parameters for lung were sufficient (r Spearman in range from 0.87 to 0.93). The
      best correlation among DVH parameters were observed between V20 and NTCP (r=0.93,
      p<0.001). On the other hand, the least but sufficient association was found for
      V30 and V20 (r=0.87, p<0.001). There was no association between clinical factors
      and RP. NTCP and V30 parameters were the best predictors of symptomatic radiation
      pneumonitis for patients after three-dimensional conformal radiotherapy of non
      small cell lung cancer.

PMID- 15739029
TI  - Imatinib mesylate in Philadelphia chromosome-positive, chronic-phase myeloid
      leukemia after failure of interferon alpha.
AB  - Imatinib mesylate (STI 571; Glivec) is a potent and selective tyrosine kinase
      inhibitor. The introduction of imatinib has chanced the philosophy of mechanisms
      of cancer therapy and already changed current management of patients with chronic
      myeloid leukemia (CML). A total of 49 patients with later chronic phase CML in
      whom previous therapy with interferon alpha had failed were treated with 400 mg
      of oral imatinib daily. Patients were evaluated for hematologic and cytogenetic
      responses. Time to progression, survival, and toxic effects were also evaluated.
      Complete hematologic responses were reported for 48 of 49 patients studied (98
      percent). The median time to a complete hematologic response was 1.2 month; 89%
      of patients who had a response did so within 4 months. Imatinib induced major
      cytogenetic responses in 73%; 62% had a complete responses. After a median follow
      up of 18 months, CML had not progressed to the accelerated or blast phases in an
      estimated 98% of patients, and 100 percent of the patients were alive. Grade 3 or
      4 nonhematologic toxic effects were manageable. No one of patients discontinued
      treatment due to of drug-related adverse events, and no treatment-related deaths
      occurred. The results of current study indicate that imatinib has a significant
      therapy benefit in CML patients in whom treatment with IFN alpha had failed.
      Therefore, has favorably changed the prognosis for patients with chronic
      myelogenous leukemia.

PMID- 15739030
TI  - Reduction of hematotoxicity and augmentation of antitumor efficacy of
      cyclophosphamide by dopamine.
AB  - Modulatory effects of dopamine (DA) on hematotoxicity and antitumor efficacy of
      cyclophosphamide (CY) were studied in Swiss mice bearing transplantable Ehrlich
      ascites carcinoma (EAC). DA was administered i.p. at a dose of 50 mg/kg/day for 5
      consecutive days beginning day 3 after tumor transplantation. CY (200 mg/kg i.p.)
      was injected 24 hour after completion of DA treatment. DA pretreatment reduced
      the suppressive effects of CY on hemoglobin, RBC, total WBC, neutrophil,
      platelet, and bone marrow nucleated cell counts. Likewise, DA partially prevented
      the CY-induced fall in pluripotent (CFU-S12) and lineage-specific stem cells for
      granulocytes (CFU-C) in bone marrow. Moreover, mice receiving a combination of DA
      and CY illustrated greater reduction in tumor volume, viable tumor cell count and
      mitotic index along with upregulation of tumor cell apoptosis than CY-only group.
      As a result, the former group demonstrated prolonged hosts survival. Thus, DA
      protected to a great extent the hematopoietic cells of tumor bearing hosts from
      the suppressive action of CY and concomitantly augmented its antitumor efficacy
      resulting in improved hosts survival.

PMID- 15739031
TI  - In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood
      acute leukemias: good activity in leukemic relapses.
AB  - Nucleoside analogues such as fludarabine and cladribine are used in therapy of
      indolent lymphomas and leukemias in adults, while cytarabine is used mainly in
      protocols for acute leukemias. Mechanisms of their activity is based on
      inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective
      of the study was the analysis of in vitro cellular drug sensitivity in childhood
      acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells
      obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54
      initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine,
      cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of
      tested cells was regarded as a value of drug resistance. Three tested nucleoside
      analogues showed highest cytotoxicity against initial ALL samples. Samples of
      relapsed ALL and initial AML were more resistant than ALL de novo ones.
      Unexpectedly, no differences were observed between initial and relapsed AML
      samples for all tested drugs, what suggests that nucleoside analogues are active
      drugs in relapsed AML, which is commonly regarded as a resistant disease. All
      tested drugs presented significant cross-resistance in each of analyzed
      subgroups. In summary, tested nucleoside analogues presented relatively good
      activity against childhood leukemias at relapse stage.

PMID- 15739032
TI  - Chromosome damage induced by benzene after the use of conventional and FISH
      chromosome painting.
AB  - The cytogenetic effects of in vitro exposure to benzene were investigated in
      cultured bovine peripheral lymphocytes. Stable and unstable chromosome
      aberrations (CA) and sister chromatid exchanges (SCE) were examined. Cultures of
      lymphocytes from two healthy donors were treated with benzene at concentrations
      of 5, 10, 50, 100, 500 and 1000 micromol.l-1 for the last 24 hours and for 2
      hours of cultivation, both without and with metabolic activation (S9). In the CA
      assays with conventional Giemsa staining for 24 hours without metabolic
      activation, no dose-dependence in the induced chromosome aberration was achieved.
      A significant elevation in the induction of CA was found only after the
      application of benzene at a dose of 100 micromol.l-1 (p<0.01). Similar results
      were observed using fluorescence in situ hybridization (FISH) method for the
      detection both of non-stable and persistent chromatid-type aberrations and in the
      SCE assay for 24 hours without S9. All the lower and higher concentrations tested
      have no positive influence on CA and SCE induction. In experiments with S9 a
      significant increase in CAs, and a dose-dependence was achieved after exposure to
      benzene for 2 hours at concentrations ranging from 50 to 500 micromol.l-1 (p<0.05
      and p<0.01, respectively).

PMID- 15739033
TI  - Role of chronic health disorders in perimenopausal fractures.
AB  - Only a few studies have examined the risk of individual chronic health disorders
      on perimenopausal (i.e., around menopause) fractures in a single study. We
      evaluated the effect of chronic illnesses on fracture rate in a prospective
      cohort study of 3,078 women. These women were a stratified sample from the
      population base of 14,220 women aged 47-56 years and residing in the province of
      Kuopio in eastern Finland in 1989. Data on physician-diagnosed chronic diseases
      were collected by a baseline questionnaire in 1989. For certain diseases,
      questionnaire information of self-reported chronic disorders were compared with
      drug reimbursement data provided by the Social Insurance Institution of Finland.
      Axial bone mineral density (BMD) measurements from the femoral neck and lumbar
      spine were performed in 1989-91. Two hundred sixty-five (265) women experienced
      at least one fracture during the follow-up period of 3.6 years (SD+/-0.78). The
      first fracture during the follow-up period was taken to be the end-point event.
      The risk of follow-up fracture for an individual health disorder was estimated
      with the Cox's proportional hazards model. Several chronic health disorders
      increased the fracture risk in perimenopausal women. However, hypertension was a
      statistically significant (p=0.018) risk factor for fracture (adjusted hazard
      ratio [HR], 1.4; 95% confidence interval [CI], 1.1-1.9), especially in overweight
      and obese (body mass index > or =28) women (HR, 2.0; 95% CI, 1.4-3.0). In
      addition, coronary heart disease (adjusted HR, 1.76; 95% CI, 1.13-2.76),
      hyperthyroidism (adjusted HR, 1.7; 95% CI, 1.0-2.9), epilepsy (adjusted HR, 2.0;
      95% CI, 1.1-3.6), alcoholism (adjusted HR, 3.5; 95% CI, 1.3-9.5) and chronic
      hepatic disease (adjusted HR, 5.2; 95% CI, 1.7-16.4) predicted fracture. BMD was
      either normal or even elevated in disease groups. However, women with a fracture
      during the follow-up usually had decreased bone density, although the difference
      was statistically significant only in women with hypertension and
      hyperthyroidism. We conclude that hypertension, coronary heart disease,
      alcoholism, epilepsy and hyperthyroidism can markedly increase the risk of
      fracture in perimenopausal women and should be taken into account when assessing
      the risk of future fracture in an individual patient. Furthermore, in contrast to
      previous data, obesity alone does not increase the risk of perimenopausal
      fracture, but in association with hypertension the risk seems to be markedly
      elevated.

PMID- 15739034
TI  - The characteristics of fractures in Polish adolescents aged 16-20 years.
AB  - The aim of the study was to identify associations between fractures in childhood
      and family, anthropometric and lifestyle factors. Among 1,246 subjects aged 16.3
      20.6 years (539 boys, 707 girls), based on a questionnaire, 869 were fracture
      free while 377 (30.26%) had fractures. Of those reporting fractures, 146 reported
      multiple fractures (12% of studied population, 39% of all fractures). More boys
      had fractures than girls (35.6% vs 24.9%, p < 0.001). Fracture sites included:
      forearm (37%), fingers (23%) wrist (16%), ankle (14%), humerus (10%), tibia (8%)
      clavicle (7%) and femoral shaft / neck (3%). Among adolescents with multiple
      fractures, 52% also reported fractures in at least one family member, compared
      with 29% of those without a fracture history. Fractures in siblings and mothers
      (but not fathers) accounted for 44% of the liability in adolescents' fractures.
      Subjects with multiple fractures reported more time at the computer than those
      without fractures and reported more time participating in team sports, and 18.6%
      avoided milk, whereas 12.4% of those without fractures reported milk-free diets.
      Using a logistic regression model, none of the lifestyle factors, except for
      computer use, were independently associated with fractures. Fractures,
      particularly multiple fractures, are common in childhood and adolescence.
      Familial clustering of fractures suggests shared genetic and environmental
      factors are responsible.

PMID- 15739035
TI  - BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive
      treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized
      and controlled trial.
AB  - Vitamin D receptor (VDR) gene polymorphisms could be considered one of the
      factors influencing the efficacy of the anti-osteoporotic treatments. In this
      multicenter, prospective, randomized and controlled trial we evaluated whether
      BsmI vitamin D receptor (VDR) genotypes influence the efficacy of antiresorptive
      treatment regimes (administered alone or in combination) in postmenopausal
      osteoporotic women. Using restriction endonuclease, we identified the BsmI VDR
      polymorphism in 1,100 postmenopausal women with osteoporosis. The women were
      randomized, taking account of genotype, into five treatment groups: (1)
      alendronate (Aln, 10 mg/day) plus raloxifene (Rlx, 60 mg/day); (2) Aln plus
      hormone replacement therapy (HRT, 0.625 mg/day conjugated equine estrogens plus
      2.5 mg/day medroxyprogesterone acetate); (3) Aln alone; (4) HRT alone; and (5)
      Rlx alone. Lumbar-spine bone mineral density (BMD) and bone turnover markers were
      measured at study entry and after 1 year of treatment. Using the general linear
      model (GLM) repeated-measures procedure, the means of BMD and bone turnover
      markers significantly differed from baseline after a period of treatment. In
      particular, the mean change from baseline for BMD was -0.034 (95% confidence
      interval [CI]: -0.037 to -0.031, P <0.001); for serum osteocalcin (OC) it was
      1.369 (95% CI: 1.289 to 1.448, P <0.001); and for urinary deoxypyridinoline (DPD)
      it was 1.322 (95% CI: 1.242 to 1.401, P <0.001), indicating a considerable
      variation before and after treatment of these indicators. In all three cases
      these effects appeared significantly influenced by treatments, genotypes, and the
      treatments*genotypes interaction term (P <0.001 each, except for the BMD and
      genotype effect with P =0.02), and not by the investigational centers involved in
      the study. In conclusion, in postmenopausal osteoporotic women, BsmI VDR
      genotypes influence the efficacy of antiresorptive drugs particularly when used
      in combination.

PMID- 15739036
TI  - The anterior approach to anterior cervical meningiomas: review illustrated by a
      case.
AB  - Anterior cervical meningiomas have traditionally been operated on by a posterior
      approach. However, several reports of an anterior approach to anterior cervical
      meningiomas and other anterior cervical intradural lesions have documented
      important advantages: large bony window of access, extradural coagulation of
      anterior blood supply to meningiomas, visualization of the intradural pathology
      in front of the spinal cord, and absence of manipulation of the spinal cord
      during resection of the lesion. In this study, the literature about anterior
      approaches to anterior cervical meningiomas is systematically reviewed and the
      advantages and disadvantages of the technique are discussed. Furthermore, a case
      of complete resection of a large anterior cervical intradural extramedullary
      meningioma from C5-7 by a three-level corpectomy with progressive postoperative
      neurological recovery is illustrated, confirming the advantages of the anterior
      approach.

PMID- 15739037
TI  - Hollow mandrin facilitates external ventricular drainage placement.
AB  - BACKGROUND: Placement of ventricular catheters is a routine procedure in
      neurosurgery. Ventricle puncture is done using a flexible ventricular catheter
      stabilised by a solid steel mandrin in order to improve stability during brain
      penetration. A correct catheter placement is confirmed after removing the solid
      steel mandrin by observation of cerebrospinal fluid (CSF) flow out of the
      flexible catheter. Incorrect placement makes further punctures necessary. The
      newly developed device allows CSF flow observation during the puncture procedure
      and in addition precise intracranial pressure (ICP) measurement. METHOD: The
      developed mandrin is hollow with a blunt tip. On one side 4-5 small holes with a
      diameter of 0.8 mm are drilled corresponding exactly with the holes in the
      ventricular catheter, allowing CSF to pass into the hollow mandrin as soon as the
      ventricle is reached. By connecting a small translucent tube at the distal
      portion of the hollow mandrin ICP can be measured without loss of CSF. The system
      has been used in 15 patients with subarachnoid haemorrhage (SAH) or
      intraventricular haemeorrhage (IVH) and subsequent hydrocephalus. FINDINGS: The
      new system improved the external ventricular drainage implantation procedure. In
      all 15 patients catheter placement was correct. ICP measurement was easy to
      perform immediately at ventricle puncture. In 4 patients at puncture no
      spontaneous CSF flow was observed, therefore by connecting a syringe and gentle
      aspiration of CSF correct placement was confirmed in this unexpected low pressure
      hydrocephalus. Otherwise by using the conventional technique further punctures
      would have been necessary. CONCLUSIONS: Advantages of the new technique are less
      puncture procedures with a lower risk of damage to neural structures and reduced
      risk of intracranial haemorrhages. Implantation of the ventricular catheter to
      far into the brain can be monitored and this complication can be overcome. Using
      the connected pressure monitoring tube an exact measurement of the opening
      intracranial pressure can be obtained performed without losing CSF.

PMID- 15739038
TI  - Factors affecting the outcome of decompressive craniectomy for large hemispheric
      infarctions: a prospective cohort study.
AB  - BACKGROUND: Although surgical decompression of large hemispheric infarction is
      often a life-saving procedure, many patients remain functionally dependent. The
      aims of this study were to identify specific factors that can be used to predict
      functional outcome, thus establish predictive criteria to reduce poor surgical
      results. METHOD: In this non-randomized prospective study, we performed
      decompressive craniectomy in 32 patients (age range, 27 to 77 years) with large
      hemispheric infarctions. Based on their modified Rankin Score (RS), which was
      calculated 6 months postoperatively, patients were divided into two functional
      groups: good (RS 0-3, n = 7) and poor (RS 4-6, n = 25). The characteristics of
      the two groups were compared using statistical analysis. FINDINGS: One-month
      mortality was 31%. However, most of the surviving patients were severely disabled
      (RS 4 or 5), and 6-month total mortality reached 50%. Increased age (> or = 60
      years) (P = 0.010), preoperative midline shift greater than 10 mm (P = 0.008),
      low preoperative Glasgow Coma Score (GCS < or = 7) (P = 0.002), presence of
      preoperative anisocoria (P = 0.032), early (within the first three days of the
      stroke) clinical deterioration (P = 0.032), and an internal carotid artery
      infarct (P = 0.069) were the positive predictors of a poor outcome.
      INTERPRETATION: We view decompressive craniectomy for space-occupying large
      hemispheric infarction as a life-sparing procedure that sometimes yields good
      functional outcomes. A dominant hemispheric infarction should not be an exclusion
      criterion when deciding to perform this operation. Early operation and careful
      patient selection based on the above-mentioned factors may improve the functional
      outcome of surgical management for large hemispheric infarction.

PMID- 15739041
TI  - Upper cranial nerve palsy resulting from spontaneous carotid dissection.
AB  - INTRODUCTION: Upper cranial nerve palsy has a variety of causes such as cerebral
      and nerve ischemia, diabetes, infectious and non-infectious meningitis,
      subarachnoid hemorrhage and intracranial aneurysm. CASE 1 : A 45-year-old man
      suffered from holocephalic headaches and a right-sided neck pain for two weeks.
      He presented to our emergency department because of a sudden ptosis of the right
      eye. On admission neurological examination revealed a right sided Horner's
      syndrome and hypesthesia of the right side of the face. Magnetic resonance
      angiography identified a circumscribed dissection of the right extracranial
      internal carotid artery originating from the carotid bifurcation. Conventional
      angiography 2 weeks later showed a nearly recanalized artery. CASE 2 : A 55-year
      old previously healthy man without cardiovascular risk factors developed right
      sided neck pain when loading a seeder with several sacks of crop. A few hours
      later he noticed a left-sided weakness. On admission a severe left sided
      hemiparesis and a mild neglect were present. Duplex sonography revealed a right
      sided distal internal carotid artery (ICA) occlusion. The next morning the
      patient complained of double vision; he had a right-sided pupil-sparing
      oculomotor palsy. The diagnosis of ICA dissection was confirmed by conventional
      angiography, at that time showing a partially recanalized ICA without involvement
      of the cavernous region by the dissection. CONCLUSION: ICA dissection must be
      included in the differential diagnosis of upper cranial nerve palsy and should be
      assessed by duplex ultrasound and magnetic resonance imaging. A possible
      explanation is nerve ischemia due to a transient or permanent interruption of the
      blood supply by compression of the vasa nervorum originating from the
      intracranial carotid artery.

PMID- 15739042
TI  - Previous antiplatelet therapy is an independent predictor of 30-day mortality
      after spontaneous supratentorial intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes.
      Despite several existing outcome prediction models for ICH, there are some
      factors with equivocal value as well as others that still have not been
      evaluated. PATIENTS AND METHODS: All patients with first ever supratentorial ICH
      presenting to our institution between December 1995 and December 2002 were
      prospectively enrolled into the study. Patients with historic modified Rankin
      Scale > 2 and those under anticoagulant treatment or with multiple ICH were
      excluded. The following parameters were analyzed in 194 consecutive patients:
      age, gender, past history of hypertension, diabetes mellitus,
      hypercholesterolemia, past history of ischemic stroke, presence of ischemic heart
      disease or cardioembolic disease, current antiplatelet treatment, current alcohol
      overuse, smoking, Glasgow Coma Scale score (GSS) at admission, volume and
      location (deep or lobar) of ICH, ventricular extension, glycemia and temperature
      at admission, and leukoaraiosis. We correlated these data with the 30-day
      mortality identifying the independent predictors by logistic regression analysis.
      RESULTS: Factors independently associated with 30-day mortality were: age,
      Glasgow Coma Scale score at admission, ICH volume, ventricular extension, glucose
      level at admission, and previous antiplatelet use. CONCLUSIONS: Apart from the
      classical outcome predictors, the previous use of antiplatelet agents and the
      glucose value at admission are independent predictors of 30-day mortality in
      patients suffering a supratentorial ICH.

PMID- 15739044
TI  - Recurrent transient ischemic attacks in a cannabis smoker.

PMID- 15739043
TI  - Detection of a novel SPG4-nonsense-mutation in a large German pedigree with pure
      spastic paraplegia.

PMID- 15739045
TI  - Sporadic Creutzfeldt-Jakob disease: a comparison of pathological findings and
      diffusion weighted imaging.
AB  - To investigate a possible relationship between the severity of pathological and
      radiological lesions in diffusion-weighted MRI (DWI) we compared DWI findings
      from 6 sequential brain MRI scans with pathological features of numerous tissue
      blocks of different cortical and subcortical regions in a case of autopsy-proven
      sporadic CJD. Whereas DWI and pathological examination revealed multifocal,
      cortical and deep hyperintensities at corresponding localizations, no correlation
      between the degree of severity of radiologically visible and pathological damage
      was found. The characteristic focal involvement and extension of lesions of the
      cortex and the basal ganglia bilaterally shown by DWI may be an argument for the
      spreading of the disease per contiguitatem.

PMID- 15739046
TI  - Plasma homocysteine is a risk factor for recurrent vascular events in young
      patients with an ischaemic stroke or TIA.
AB  - OBJECTIVES: Young patients with an ischaemic stroke or transient ischaemic attack
      (TIA) often have no vascular risk factors. Hyper-homocysteinaemia is an
      established risk factor for stroke in elderly patients but it is uncertain
      whether it is also important for the prognosis of young ischaemic stroke and TIA
      patients. We examined the possible effect of the plasma homocysteine level on the
      risk of recurrent vascular events in patients between 18 and 45 years of age.
      METHODS: The study population consisted of 161 consecutive patients with a recent
      cerebral infarction or TIA. Data on the primary event and the homocysteine level
      were collected retrospectively from hospital records. General practitioners and
      patients were contacted by telephone to record vascular events and the type of
      medication used during the follow-up period. Vascular events included cerebral
      infarction, TIA, pulmonary embolism, venous thrombosis, myocardial infarction and
      peripheral arterial disease. RESULTS: A Kaplan- Meier curve showed a dose effect
      relationship between event-free survival time and tertiles of the homocysteine
      level (Log rank statistic 5.91; p=0.05). The Cox hazard ratio, after adjustment
      for homocysteine lowering treatment, was 1.7 (95 % CI, 1.1 to 2.8) for any
      vascular outcome event, 1.9 (95% CI, 1.1 to 3.0) for arterial outcome events and
      1.8 (95 % CI, 1.1 to 2.9) for cerebral outcome events. CONCLUSIONS: In spite of
      our small number of outcome events we found a significant association at the 95%
      confidence level between homocysteine level and the risk of recurrent vascular
      events in young patients with an ischaemic stroke or TIA. The association is of
      the same magnitude as in elderly people.

PMID- 15739048
TI  - Maintenance of the internal environment in total artificial heart (TAH)
      recipients during long-term pumping.
AB  - Sixty-six long-term experiments were performed on animals (65 calves, 1 goat)
      after implantation with a total artificial heart (TAH). Animal survival ranged
      from 30 to 314 days using TAH devices ranging from the TNS-BRNO-II to the TNS
      BRNO-VIIII. In these experiments some basic problems were studied which need to
      be overcome to achieve the optimal physiological status of the animal, the
      optimal maintenance of the internal environment, and the long-term survival of
      TAH recipients. The problem areas studied were: the vasomotor regulation of the
      periphery, the prevention of calcification of the driving diaphragms, the optimal
      regulation of homeostasis, and the pathogenesis and prevention of infection. The
      basic precondition for the experiments was the problem-free implantation of a TAH
      and the subsequent optimal method of postoperative care was investigated. By the
      gradual multifactorial solution of these individual problems, the prolongation of
      the survival period of experimental animals was achieved. The definite solution
      and elucidation of some complications during long-term survival is still an open
      problem because the multifactorial events that influence long-term TAH survival
      are often very complicated and can sometimes only be solved by overcoming
      numerous obstacles as a result of the deep functional interrelationships of the
      disorders present.

PMID- 15739047
TI  - Frontotemporal white matter changes in amyotrophic lateral sclerosis.
AB  - Cognitive dysfunction can occur in some patients with amyotrophic lateral
      sclerosis (ALS) who are not suffering from dementia. The most striking and
      consistent cognitive deficit has been found using tests of verbal fluency. ALS
      patients with verbal fluency deficits have shown functional imaging abnormalities
      predominantly in frontotemporal regions using positron emission tomography (PET).
      This study used automated volumetric voxel-based analysis of grey and white
      matter densities of structural magnetic resonance imaging (MRI) scans to explore
      the underlying pattern of structural cerebral change in nondemented ALS patients
      with verbal fluency deficits. Two groups of ALS patients, defined by the presence
      or absence of cognitive impairment on the basis of the Written Verbal Fluency
      Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were
      compared with healthy age matched controls (n=12). A comparison of the ALSi group
      with controls revealed significantly (p<0.002) reduced white matter volume in
      extensive motor and non-motor regions, including regions corresponding to
      frontotemporal association fibres. These patients demonstrated a corresponding
      cognitive profile of executive and memory dysfunction. Less extensive white
      matter reductions were revealed in the comparison of the ALSu and control groups
      in regions corresponding to frontal association fibres. White matter volumes were
      also found to correlate with performance on memory tests. There were no
      significant reductions in grey matter volume in the comparison of either patient
      group with controls. The structural white matter abnormalities in frontal and
      temporal regions revealed here may underlie the cognitive and functional imaging
      abnormalities previously reported in non-demented ALS patients. The results also
      suggest that extra-motor structural abnormalities may be present in ALS patients
      with no evidence of cognitive change. The findings support the hypothesis of a
      continuum of extra-motor cerebral and cognitive change in this disorder.

PMID- 15739049
TI  - Computational analysis of the three-dimensional hemodynamics of the blood sac in
      the twin-pulse life-support system.
AB  - Blood flow in the twin-pulse life-support system (T-PLS) pulsatile blood pump was
      simulated using a three-dimensional rigid body-fluid-solid interaction model.
      This model can delineate the blood flow in the T-PLS resulting from operation of
      a moving actuator. The numerical method used in this study was a commercial
      finite element package called ADINA. We used a contact and fluid-solid
      interaction model to compute the blood hemodynamics in the sac. Blood flow is
      generated by the motion of the actuator, which strongly interacts with the solid
      material surrounding the blood. To obtain basic bioengineering data on the
      optimum operation of the T-PLS, we simulated four models in which the actuator
      moved at different speeds and investigated both the flow pattern and the
      distribution of shear stress. During the contraction phase, a strong axial flow
      is observed around the outlet, whereas there is stagnant flow around the inlet.
      The maximum shear stress in each model depends on the operation mode; however,
      all four models have similar flow rates. The sinusoidal mode exhibited the lowest
      maximum shear stress and is thus considered the most efficient of the four
      operating modes.

PMID- 15739050
TI  - In vivo evaluation of poly(N-isopropylacrylamide) (PNIPAM)-grafted gelatin as an
      in situ-formable scaffold.
AB  - We examined whether poly(N-isopropylacrylamide)-grafted gelatin (PNIPAM-gelatin)
      with a lower critical solution temperature of approximately 34 degrees C, which
      was prepared by quasi-living radical graft polymerization, can serve as an in
      situ-formable three-dimensional extracellular matrix or cell scaffold. A mixture
      of fibroblasts stained with fluorescent dye and PNIPAM-gelatin in Dulbecco's
      modified Eagle's medium solution was injected into the subcutaneous tissue of
      Wistar rats, and immediately formed a white, opaque cell-incorporated gel.
      Fibroblasts immediately after injection were spherical in shape and were
      homogeneously distributed in the gel. Fibroblasts in the gel 2 weeks after
      injection had spread and proliferated. One day after injection, many macrophages
      and neutrophiles were observed around the gel. As the implantation period
      proceeded, the inflammation reaction subsided. One week after injection,
      fibroblasts in the native tissue and macrophages migrated into the gel. From 6 to
      12 weeks after injection, some degree of calcification in the solid tissue was
      intermittently observed. The weight of the gel 6 weeks after implantation was
      reduced to almost one-half of the weight of the originally injected sample. The
      potential usefulness of PNIPAM-gelatin as an injectable scaffold is discussed.

PMID- 15739051
TI  - Surface modification of poly(L: -lactic acid) affects initial cell attachment,
      cell morphology, and cell growth.
AB  - The object of this study was to develop a highly porous scaffold to be used in
      regeneration of blood vessels, nerves, and other hollow tissues with small
      openings. Using the phase-inversion method and a mixture of water and methanol as
      a coagulating agent, we prepared highly porous flat membranes from poly(L: 
      lactic acid) (PLLA) with numerous pores both on the surface and in the interior
      of the membranes. Chinese hamster ovary (CHO) cells were cultured on the
      membranes to evaluate initial cell adhesion, cell proliferation, and cell
      morphology. Adhesion of CHO cells to PLLA was poor: the cells adhered at
      approximately half the rate observed with a tissue culture polystyrene dish
      (TCPS). In contrast, adhesion of cells to PLLA treated with a low-temperature
      oxygen plasma was good; the adhesion rate was the same as that on TCPS. The rate
      of cell proliferation on the treated membranes was no different from that on the
      nontreated membranes, but cell morphologies were quite different. The cells on
      the nontreated membranes were small and round and proliferated separately from
      one another. In contrast, the cells on the plasma-treated membranes proliferated
      in close contact with other cells, spreading out extensively in sheet-like
      formations. Since the plasma treatment not only accelerated cell adhesion but
      also enabled cells to proliferate in the form of sheets resembling biological
      tissue, we believe that oxygen-plasma treatment is extremely effective for
      modifying surfaces of materials used for tissue regeneration.

PMID- 15739052
TI  - Effect of heparin addition on expansion of cord blood hematopoietic progenitor
      cells in three-dimensional coculture with stromal cells in nonwoven fabrics.
AB  - Primary human cord blood mononuclear cells (CB MNCs) were inoculated into layers
      of primary human bone marrow stromal cells prepared in a nonwoven fabric porous
      carrier [three dimensional (3-D)] or on a dish [two dimensional (2-D)] using a
      cytokine-free medium and were cultured for 7 days with or without the addition of
      heparin. The number of progenitor cells increased threefold during the 3-D
      coculture, whereas it decreased in the 2-D culture. Heparin addition to the 3-D
      coculture further increased the number of progenitors twofold, whereas the
      addition of desulfated heparin had no effect. The heparin effect was also
      observed in a 3-D culture of CB MNCs without stromal cells when conditioned
      medium was employed. The coating of the carrier with N-(O-beta-(6-O
      sulfogalactopyranosyl)-6-oxyhexyl)-3,5-bis (dodecyloxy)-benzamide instead of
      heparin addition also increased the number of progenitor cells in the 3-D culture
      of CB MNCs without stromal cells when the conditioned medium was employed. The 3
      D coculture constructed with nonwoven fabrics and stromal cells was clearly
      superior to the 2-D culture because of the expansion of CB hematopoietic
      progenitor cells without cytokine addition. Heparin addition to the 3-D coculture
      further increased the number of progenitor cells, which may result from a
      synergistic effect of soluble cytokines produced by stromal cells with the sulfur
      group of heparin.

PMID- 15739053
TI  - Consideration of prosthesis-patient mismatch and left ventricular mass regression
      after implantation of the Carpentier-Edwards pericardial valve in elderly
      Japanese patients: body surface area may be irrelevant.
AB  - The assessment of prosthesis patient mismatch (PPM) for small aortic annulus is
      important for prognosis after aortic valve replacement (AVR). Recent
      investigations have demonstrated that PPM occurs in AVR patients with an indexed
      effective orifice area (iEOA) of less than 0.85 cm2/m2. We investigated
      hemodynamic performance and left ventricular mass (LVM) regression after AVR.
      Eighteen patients who underwent AVR using a 19-mm Carpentier-Edwards pericardial
      (CEP) valve without annular enlargement were studied by echocardiography and
      Doppler examination 4 months after AVR. Patients were divided into two groups on
      the basis of their body surface area (BSA); the smaller BSA (group S, 1.14-1.36
      m2, nine patients) and the larger BSA (group L, 1.40-1.83 m2, nine patients). Of
      these 18 patients, ten underwent isolated AVR, and five underwent AVR with
      coronary artery bypass graft; (i.e., double valvular replacement, AVR with maze
      procedure, and AVR with mitral valvulophasty. There were no statistically
      significant differences between the two groups, except for age (group S, 78.3+/
      2.5 years; group L, 73.6+/-2.4 years). There was no significant difference for
      the iEOA during the late phase at rest (group S, 1.10+/-0.26 cm2; group L, 1.02+/
      0.28 cm2). However, there was a significant difference for the LVM regression
      between the preoperative and postoperative values (group S, 243+/-23.6 mg/cm2
      [pre], 190+/-16.9 mg/cm2 [post]; group L, 302+/-13.7 mg/cm2 [pre], 199+/-16.7
      mg/cm2 [post]). In elderly Japanese patients with a BSA of less than 18 m2, we
      demonstrated LVM regression and avoidance of PPM after implantation of the aortic
      19-mm CEP valve.

PMID- 15739054
TI  - Deterioration of suture materials at prosthetic-host anastomoses.
AB  - We experienced a case of polypropylene suture rupture at anastomosis 5 years
      after fabric vascular graft implantation. Under a scanning electron microscope,
      the removed suture had a tapering-off breakage at the end and tortoiseshell-like
      deep cracks near the end. The tapered stump indicated that the suture had been
      stretched out gradually and had finally fractured.

PMID- 15739055
TI  - Development of an artificial synapse using an electrochemical micropump.
AB  - Improving the resolution of artificial sensory organs requires an interface that
      receives external information from electronic circuits and stimulates appropriate
      neurons individually in response to that information. The method of electric
      stimulation in available artificial sensory organs is fairly nonselective;
      therefore, we developed a method of chemical stimulation of neurons using a
      neurotransmitter containing an electrochemical micropump powered by the bubbling
      that occurs during water electrolysis. The micropump contains a glass nozzle with
      a tip 10 microm in diameter. Two blackened platinum electrodes for the
      electrolysis were inserted into the body of the pump, which was filled with
      neurotransmitter solution. The distance between a neuron of the gastropod Aplysia
      and the tip of the nozzle was adjusted to about 100 microm. A potential
      difference of 3.0 V was applied to the electrodes to propel the solution toward
      the neuron while its membrane potential was monitored. Administration of 1-mM
      acetylcholine to a resting neuron caused neural firing only when the voltage was
      applied for 0.5 s and without a time lag. During administration of 50-mM gamma
      aminobutyric acid to spontaneously firing neurons, the firing disappeared with a
      time lag of 1 s after application of 3.0 V. We concluded that an electrochemical
      micropump can be applied for rapid neurotransmitter administration to control the
      excitation and inhibition of neurons. This simple pump can be miniaturized to
      create "synapses" in artificial sensory organs.

PMID- 15739056
TI  - Psychosocial care of cancer patients--international differences in definition,
      healthcare structures, and therapeutic approaches.
AB  - Psychosocial oncology has become an important part of oncological care in many
      countries, but few international comparisons of the establishment of psychosocial
      oncology have been undertaken to date. This survey was conducted to establish the
      current conditions in which psychosocial oncology is implemented with reference
      to medical care, research, education and training. A semistructured questionnaire
      was sent to as many as four psychosocial oncology experts from 64 countries.
      Information was returned by 45 experts from 38 countries. As a relatively new
      discipline, psychosocial oncology is understood to be an integral part of
      oncology care, but has only been fully integrated in a few countries at present.
      In contrast, there are a large number of evidence-based interventions available
      for cancer patients and their families. Improvements are necessary in the
      transfer of empirical results into clinical practice, and in the development of
      guidelines to ensure adequate psychosocial care for oncology patients.

PMID- 15739058
TI  - [Reoperation for thyroid cancer].
AB  - Reoperation for thyroid cancer needs to consider patient-, tumor- and therapy
      related aspects as well as present diagnostic results. Reoperation because of
      thyroid remnants, persistence of the primary tumor and lymph node metastasis
      (completion surgery) has to be distinguished from reoperation due to locoregional
      recurrence (primary tumor, lymph nodes). The primary surgical strategy should
      avoid the need for reoperation. The extent of reoperation is related to the
      extent of primary surgery, stage, and distant metastasis. The timing and
      indication of reoperation for differentiated thyroid carcinoma in an
      interdisciplinary multimodal treatment setting depends on diagnostic radioiodine
      scans and radioiodine therapy. Long-term, recurrence-free survival is achieved by
      sufficiently radical surgery with acceptable morbidity, including all additive or
      adjuvant treatment options.

PMID- 15739057
TI  - [Recurrent operations on the adrenal glands].
AB  - Repeat adrenalectomy may be required due to ipsilateral recurrence of benign or
      malignant adrenal tumors after previous total or subtotal adrenalectomy. Even for
      multivisceral resection in patients with adrenocortical carcinoma, complete
      resection of local recurrent tumor offers results similar to those of primary
      resection (5-year survival 40-60%). In contrast, since no benefit on long-term
      survival has been shown so far by tumor debulking, palliative tumor resection
      should only be performed individually for control of severe endocrine symptoms.
      The effect of endoscopic adrenalectomy in patients with large tumors (>5 cm) or
      suspected malignancy has still not been well examined. Further studies are
      required. In any case, during open or endoscopic approach, tumor spillage must be
      avoided to prevent local tumor cell implantation. Following subtotal
      adrenalectomy, the risk of ipsilateral recurrence correlates with disease, follow
      up, localization, size of the adrenal remnant, and, in case of familial
      pheochromocytoma, probably with genotype.

PMID- 15739060
TI  - [Clinical value of percutaneous nephrolithotomy].
AB  - The introduction of percutaneous nephrolithotomy (PNL) marked a turning point in
      the interventional treatment of nephrolithiasis. For the first time, the
      minimally invasive removal of larger kidney stones, which had previously required
      open surgery, became possible. With the increasing use of extracorporeal shock
      wave lithotripsy (SWL) during the 1980s, PNL lost clinical importance. However,
      since SWL has revealed its limitations, and both the patients' wishes and
      economic demand require a fast stone removal, the importance of PNL has risen
      again. Given the correct indications and performance, PNL is an efficient
      treatment modality reaching stone free rates of up to 100%. When PNL is performed
      by an experienced urologist, complications are low and can be managed
      conservatively in most cases. The most important step in the performance of a PNL
      is the anatomically correct puncture of the kidney gaining optimal access to the
      stone. To reach this, a lower calyx is punctured whenever possible, under
      combined sonographic and fluoroscopic guidance.

PMID- 15739061
TI  - [A rare case of isolated prostate metastasis from primary pancreatic cancer].
AB  - An otherwise healthy 66 year old male presented with a suspicious intraprostatic
      lesion detected by digito-rectal examination. Serum PSA levels were normal. A CT
      scan of the abdomen revealed a nondistinctive mass within the pancreatic head. A
      transrectal biopsy confirmed the intraprostatic lesion as a metastatic lesion
      from pancreatic cancer. Therefore, we report this unusual case of a primary
      pancreatic carcinoma, clinical stage IV, which led to metastases in the liver and
      prostate.

PMID- 15739059
TI  - [Present treatment strategies for rectal carcinoma].
AB  - In the last ten years, considerable progress has been achieved in the treatment
      of rectal cancer. According to improved interdisciplinary staging, rectal
      carcinomas can be treated based on a stage-dependent concept: "low-risk" pT1
      (G1/G2) carcinomas can be cured by local full wall excision, while "high-risk"
      pT1 (G3/G4) and pT2 carcinomas require transabdominal resection. In contrast,
      locally advanced rectal cancers in cUICC-II/-III stages (T3/T4 or N(+)) should
      receive long-term, 5-FU-based, neoadjuvant chemoradiotherapy according to the
      excellent results of the CAO/AIO/ARO-94 trial of the German Rectal Cancer Study
      Group. High-quality resection must be based on radical oncologic principles such
      as "no-touch" technique, radicular dissection of vessels, and total mesorectal
      excision. Multimodal treatment is completed with adjuvant 5-FU-based
      chemotherapy. This therapeutic approach led to a reduction in the 5-year local
      recurrence rate to 6% and disease-free survival of approximately 68% in advanced
      rectal cancer (overall survival: 76%).

PMID- 15739062
TI  - [Activity of antiseptic catheter lubricants against methicillin-resistant
      Staphylococcus aureus (MRSA)].
AB  - In recent years, general and urinary tract infections caused by methicillin
      resistant Staphylococcus aureus (MRSA) have became an increasing problem
      worldwide. Catheterization of the urinary bladder is one of the most significant
      risk factors for MRSA contamination of the urine. In vitro tests have documented
      the antimicrobial activity of the catheter lubricants Instillagel and Endosgel
      against MRSA specimens within 5 min. These findings support recommending the use
      of these lubricants in high-risk patients in hospitals and old people's homes for
      prophylaxis of MRSA bacteriuria.

PMID- 15739063
TI  - [Hereditary multiple exostoses. Molecular genetic analysis of the EXT1 gene in an
      unusual family].
AB  - Hereditary multiple exostosis (HME), a disorder inherited in an autosomal
      dominant manner, is characterized by multiple projections of bone, mainly at the
      extremities. The risk of malignant transformation of the exostoses is estimated
      to be up to 2%. The most common underlying cause of the disease involves
      mutations in either the EXT1 or the EXT2 gene. We report on the clinical and
      molecular findings in a family affected with HME.A mother and her three children
      from different partnerships, all clinically diagnosed with HME, were referred for
      genetic counseling. Subsequently, molecular analysis of the EXT1 gene was
      performed according to standard procedures. We identified a mutation in the EXT1
      gene in all four affected family members (delA in codon 133). This mutation has
      not been previously described and is suggested to cause the disease in this
      family. Identification of disease causing mutations in patients with HME and
      their relatives can help to improve the clinical management of tumor prevention,
      early tumor detection, and orthopedic therapy.

PMID- 15739064
TI  - Metabolic pathway structures for recombinant protein synthesis in Escherichia
      coli.
AB  - Escherichia coli is a valuable commercial host for the production of heterologous
      proteins. We used elementary mode analysis to identify all possible genetically
      independent pathways for the production of three specific recombinant proteins,
      green fluorescent protein, savinase and an artificial protein consisting of
      repeating units of a five-amino-acid cassette. Analysis of these pathways led to
      the identification of the most efficient pathways for the production of each of
      these proteins. The results indicate that the amino acid composition of expressed
      proteins has a profound effect on the number and identity of possible pathways
      for the production of these proteins. We show that several groups of elementary
      modes produce the same ratio of biomass and recombinant protein. The pattern of
      occurrence of these modes is dependent on the amino acid composition of the
      specific foreign protein produced. These pathways are formed as systemic
      combinations of other pathways that produce biomass or foreign protein alone
      after the elimination of fluxes in specific internal reversible reactions or the
      reversible carbon dioxide exchange reaction. Since these modes represent pathway
      options that enable the cell to produce biomass and protein without utilizing
      these reactions, removal of these reactions would constrain the cells to utilize
      these modes for producing biomass and foreign protein at constant ratios.

PMID- 15739065
TI  - The effect of standard lumbar discectomy on segmental motion: 5-year follow-up
      using radiostereometry.
AB  - We measured the effects of lumbar discectomy on segmental motion over a period of
      5 years. Twenty-four patients with lumbar disc herniation were treated by
      standard lumbar discectomy at the L4-L5 or L5-S1 level. Peroperatively, tantalum
      markers were inserted into L4, L5, and the sacrum. Radiostereometric analysis was
      performed at discharge from hospital and 5 years postoperatively. The treated
      level was compared with the corresponding untreated level. Thus, patients who had
      discectomy at the L4-L5 level served as controls for patients with L5-S1 lesions
      and vice versa. The relative rotation and translation in relation to the three
      cardinal axes were calculated. Inducible displacements over the two discs were
      calculated between the supine and standing positions. At the L4-L5 level, there
      were no differences in inducible displacements between the operated and control
      levels at discharge or 5 years postoperatively. At the L5-S1 level we found
      decreasing inducible movement in the sagittal plane over time for discectomy
      patients. The reason for decreasing mobility over time after discectomy at the L5
      S1 but not at the L4-L5 level is unknown. Mechanical factors caused by the more
      vertical orientation of the L5-S1 disc in combination with degenerative changes
      could be one explanation.

PMID- 15739066
TI  - Anoxia tolerance and freeze tolerance in hatchling turtles.
AB  - Freezing survival in hatchling turtles may be limited by ischemic anoxia in
      frozen tissues and the associated accumulation of lactate and reactive oxygen
      species (ROS). To determine whether mechanisms for coping with anoxia are also
      important in freeze tolerance, we examined the association between capacities for
      freezing survival and anoxia tolerance in hatchlings of seven species of turtles.
      Tolerance to freezing (-2.5 degrees C) was high in Emydoidea blandingii,
      Chrysemys picta, Terrapene ornata, and Malaclemys terrapin and low in Graptemys
      geographica, Chelydra serpentina, and Trachemys scripta. Hatchlings survived in a
      N(2) atmosphere at 4 degrees C for periods ranging from 17 d (M. terrapin) to 50
      d (G. geographica), but survival time was not associated with freeze tolerance.
      Lactate accumulated during both stresses, but plasma levels in frozen/thawed
      turtles were well below those found in anoxia-exposed animals. Activity of the
      antioxidant enzyme catalase in liver increased markedly with anoxia exposure in
      most species, but increased with freezing/thawing only in species with low freeze
      tolerance. Our results suggest that whereas oxygen deprivation occurs during
      somatic freezing, freeze tolerance is not limited by anoxia tolerance in
      hatchling turtles.

PMID- 15739067
TI  - Intramedullary spinal cord gangliocytoma: case report and a review of the
      literature.
AB  - We present a case of intramedullary spinal gangliocytoma in a 19-year-old woman
      who presented with a long history of hyperhidrosis of the face and neck areas and
      intermittent pain of the hands. The tumor involved the cervico-thoracic region of
      the spinal cord from C7-T3. The patient underwent debulking of the lesion and
      remains neurologically stable at two years follow-up. A discussion of this case
      is followed by a review of the literature surrounding this rare
      clinicopathological entity.

PMID- 15739068
TI  - Dorsal intramedullary dermoids.
AB  - We report a case of a 31-year-old woman with an intramedullary thoracic dermoid,
      who had progressive spastic paraparesis in her lower extremities over a period of
      three years, as well as loss of bowel and bladder control. She had been operated
      for "spina bifida" at three days of age but had no neurologic deficit. MRI of the
      thoracic spine showed an intramedullary hypointense lesion at T7-T8, associated
      with an intramedullary lipoma at a higher level. Intracapsular resection of an
      intramedullary dermoid cyst was performed. We review the literature on
      intramedullary dermoids differentiating them from the more common, but still
      rare, lumbosacral subdural juxtamedullary dermoids. We discuss the associated
      malformations with these lesions, as well as their pathophysiology and treatment.
      Although uncommon, dorsal intramedullary dermoids should be suspected and treated
      in a timely manner, especially in presence of other congenital anomalies.

PMID- 15739069
TI  - Cystic versus solid vestibular schwannomas: a series of 80 grade III-IV patients.
AB  - Cystic acoustic neuromas are less frequent than solid ones and present different
      clinical and radiological features. Cystic schwannomas are larger, show a shorter
      clinical history and a different risk of postoperative complications. This study
      was designed to compare surgical results and complications of solid and cystic
      vestibular schwannomas of matching size operated upon via either a retrosygmoid
      or a translabyrinthine approach. The study included 80 patients presenting with
      grade III and IV acoustic vestibular schwannomas referred to the Neurosurgical
      and ENT team in the Department of Neuroscience of Torino, Italy. Twenty-six were
      cystic and 54 were solid tumours. Clinical history, surgical results and
      complications were compared between the two groups. In cystic tumors, rapid
      clinical worsening is common, due to sudden expansion of cystic elements. Tighter
      adherences are found between cystic tumours and nervous elements (particularly
      brainstem and possibly facial nerve), once compared to solid ones. Operative
      morbidity appears to be higher in cystic tumours. A wait and see policy should
      not to be applied to patients with cystic tumours. Careful technique, possibly
      sharp dissection, to divide the tumour adherences from the nervous tissue must be
      employed, in order to avoid lesions on brainstem veins and traction on a thin
      facial nerve. Severe complications may be caused by the excessive efforts to
      dissect brainstem adherences.

PMID- 15739070
TI  - Seasonal occurrence and metrical variability of Gyrodactylus rhodei Zitnan 1964
      (Monogenea, Gyrodactylidae).
AB  - The seasonal dynamics of Gyrodactylus rhodei, a monogenean ectoparasite of
      bitterling (Rhodeus sericeus), was studied from June 2000 to May 2001 in the
      Kyjovka River, Czech Republic. A negative relationship between prevalence and
      intensity of infection of G. rhodei and water temperature was found. Metrical
      variability of the hard parts of the parasite haptor was studied throughout the
      sampling season. A negative relationship between water temperature and the size
      of the hard parts of the G. rhodei haptor was evident in the measurements of the
      total length of the marginal hooks, the sickle length of marginal hooks, anchors,
      anchor point and root, the width of the ventral bar and the membrane processes.
      Sequences of the partial ITS (rDNA) of specimens collected during the cold and
      warm seasons were analysed. Sequences of all studied parasite specimens were
      identical and there was no evidence of intraspecific variability in the sequenced
      region.

PMID- 15739071
TI  - Ecdysis of Oesophagostomum: possible involvement of eicosanoids and development
      of a bioassay.
AB  - Bioassays were developed and applied to test the role of eicosanoids and pH
      changes in ecdysis of Oesophagostomum dentatum. Exsheathment (80-100%) was
      achieved by subjecting third-stage larvae (L3) either to chlorine (hypochlorite
      assay) for 5 min or by incubating them in HCl followed by addition of NaHCO3 (pH
      change assay) with subsequent cultivation at 38.5 degrees C/10% CO2 for 1 week.
      Addition of the lipoxygenase (LOX) inhibitor diethylcarbamacine (DEC) to the
      larvae resulted in a reduction of the exsheathment rates which could be restored
      by the addition of leukotrienes (LT)B4, LTC4, LTD4 and LTE4. Addition of the
      cyclooxygenase (COX) inhibitor acetylsalicylic acid (ASA) also resulted in
      decreased exsheathment rates both in the hypochlorite and in the pH-change assays
      in a dose-dependent manner. However, the primary COX products (prostaglandins)
      were not able to reverse this effect, in contrast to LTC4. It was concluded that:
      (1) both tests are suitable for bioassaying the effect of substances on
      exsheathment, and (2) eicosanoids involved in the control of exsheathment of L3
      of O. dentatum are primarily LT.

PMID- 15739072
TI  - Search for new prototypes for the chemotherapy of filariasis: a chemotherapeutic
      and biochemical approach.
AB  - The antifilarial activity of two coumarin derivatives (A, B) and three glycosyl
      amine derivatives (D, E, F) was evaluated against a subperiodic strain of human
      lymphatic filarial parasite Brugia malayi by the intraperitoneal route at 50
      mg/kg for 5 consecutive days. Of these, the two sugar derivatives (D and E) were
      selected for evaluation by the oral route based on their microfilaricidal (mild),
      macrofilaricidal and female worm sterilization efficacy using the i.p. route of
      administration. Compound E was finally selected for combination therapy on the
      basis of its microfilaricidal and embryostatic action by the oral route and its
      spectrum of activity against micro- and macrofilariae including embryostatic
      activity by the i.p. route. In addition, E also significantly inhibited the
      parasite DNA topoisomerase II. Compound A, in contrast, led to an enhanced adult
      worm burden. Compound B was toxic by the i.p. route, killing all of the treated
      animals before completion of the experiment. Some of these compounds demonstrated
      significant antifilarial efficacy of varying degree when tested in vitro
      Compounds B, D and F also killed adult B. malayi in vitro at 100 muM while 50 muM
      resulted in very slow motility of worms. Compound E in combination with a
      promising macrofilaricidal benzopyran derivative reported by us recently
      (compound C) did not show any synergistic or additive effect. These two compounds
      (C and E) individually on oral administration with either DEC or ivermectin
      significantly improved microfilaricidal efficacy in terms of intensity and
      duration of suppressed microfilaraemia. The combination of DEC with compound E
      demonstrated marginal enhancement in adulticidal efficacy, however, the
      embryostatic effect of the duo was significantly higher than that exerted by the
      individual agents. It may thus be inferred that in the absence of an adulticidal
      antifilarial drug, the use of potential antifilarials in combination with the
      standard filaricides may yield better results.

PMID- 15739073
TI  - [Necessity for blood transfusion in head and neck surgery].
AB  - INTRODUCTION: Sometimes, use of blood products is necessary in head and neck
      surgery, but blood transfusion also entails risks for the patients and causes
      high costs for the department. Therefore, we examined the surgical procedures in
      our department and analysed how often transfusion of blood was necessary and
      which expenses were incurred. METHODS: Of 3989 operations performed in 1989, 187
      patients were found to be at an increased risk for blood loss. The costs for
      blood group analysis (euro 23.16), cross-testing (euro 13.91) and the transfusion
      itself (euro 70.35) were estimated in each patient. RESULTS: In 1998 more than
      60% of the 187 patients had undergone extensive head and neck surgery for
      advanced squamous cell carcinoma. Only 17 patients (<15%) received nearly 45% of
      all units of stored blood transfused that year. In patients who had undergone
      skull base surgery, the probability of receiving blood was 30%. The transfusion
      related costs were estimated to be euro 20,000 during the observation period.
      Potential savings could have been achieved in cross-testing. CONCLUSION:
      Preparations should be done on an individual basis. Such preparations are
      sometimes unnecessary even in patients undergoing surgical procedures with a high
      risk for blood loss.

PMID- 15739074
TI  - The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and
      cognition: a comparison.
AB  - RATIONALE: Antagonists at the metabotropic glutamate 5 (mGlu5) receptor produce
      robust anxiolytic effects in a number of rat tests. However, there is evidence
      that mGlu5 receptor antagonists may also impair working memory and spatial
      learning following intracerebroventricular administration. OBJECTIVES: The aim of
      this study is to compare the effect of the potent and selective mGlu5 receptor
      antagonist, 2-methyl-6-(phenylethynyl)-piperidine (MPEP), administered
      systemically on rodent tests of cognition and anxiety. METHODS: MPEP was assessed
      in the following rodent tests, 60 min following oral administration: Geller-
      Seifter conflict, conditioned emotional response (CER), Vogel conflict, delayed
      match to position (DMTP) and Morris water maze. Diazepam was also tested as a
      comparator. RESULTS: MPEP had a significant anxiolytic effect, comparable in
      magnitude to diazepam, at 10--30 mg/kg in the two conflict and CER tasks. There
      was no effect of MPEP up to 30 mg/kg on working memory in the DMTP task, but at
      100 mg/kg, there was a significant reduction in choice accuracy at the longest
      delay interval (24 s). MPEP (3--30 mg/kg) did not significantly impair spatial
      learning in the Morris water maze, although during the last probe trial, 30-mg/kg
      treated rats were significantly less accurate than controls. In contrast,
      diazepam significantly impaired performance in both the DMTP and Morris water
      maze tests. Assessment of plasma and brain concentration of MPEP approximately 75
      min following oral administration showed a dose linearity from 3 to 30 mg/kg and
      good brain penetration, i.e. a brain/plasma ratio of 3.1. CONCLUSIONS: Oral
      administration of the selective mGlu5 receptor antagonist MPEP induces a robust
      anxiolytic-like effect in rat conflict tests comparable to that seen with
      diazepam, but in contrast to diazepam, MPEP does not impair working memory or
      spatial learning at anxiolytic doses.

PMID- 15739075
TI  - Role of withdrawal in reinstatement of morphine-conditioned place preference.
AB  - RATIONALE: Relapse is a major characteristic of drug addiction and the primary
      problem in treating drug abuse. Based on the negative reinforcement view of
      addiction, in which the motivation to take drugs is thought to result from the
      desire to avoid the aversive effect of drug withdrawal, it has been theorized
      that withdrawal symptoms play a major role in the maintenance of and relapse to
      drug taking. However, the role of withdrawal in relapse has not yet been
      systemically investigated in the reinstatement model. OBJECTIVES: Using a
      conditioned place preference (CPP) paradigm, we examined the role of different
      morphine withdrawal states (spontaneous withdrawal, naloxone-precipitated
      withdrawal, and conditioned withdrawal) in relapse to drug seeking. METHODS: Rats
      alternately received morphine (10 mg/kg, s.c.) and saline for 8 days to acquire
      the CPP. The morphine CPP disappeared after a 2-week extinction phase of saline
      paired training. Rats were then chronically administered morphine to induce
      physical dependence. The different withdrawal states were induced and their roles
      in the reinstatement of extinguished CPP were assessed. During conditioned
      withdrawal, trunk blood samples were taken and the corticosterone level was
      measured by radioimmunoassay. To examine the role of corticotropin-releasing
      factor (CRF) receptor antagonist on conditioned-withdrawal-induced reinstatement
      of CPP, different doses of alpha-helical CRF (0.1 and 1 mug, i.c.v.) were
      administered 30 min prior to the CPP testing. RESULTS: The results show that
      morphine spontaneous withdrawal and naloxone-precipitated morphine withdrawal
      were ineffective in reinstatement morphine CPP. However, the withdrawal cues
      significantly elicited the reinstatement of CPP and increased corticosterone
      level. Moreover, pretreatment with the CRF receptor antagonist alpha-helical CRF
      (1 mug, i.c.v.) significantly attenuated the effects of withdrawal cues on
      reinstatement of CPP and corticosterone levels. CONCLUSION: These findings
      demonstrate that the cues associated with previous drug withdrawal play a major
      role in drug relapse and that activation of the CRF receptor is involved in
      conditioned-withdrawal-induced reinstatement. The present study suggests that CRF
      receptor antagonists might be of value in the treatment and prevention of relapse
      to drug seeking after long-term abstinence.

PMID- 15739076
TI  - Differential cognitive effects of Ginkgo biloba after acute and chronic treatment
      in healthy young volunteers.
AB  - RATIONALE: Acute doses of Ginkgo biloba have been shown to improve attention and
      memory in young, healthy participants, but there has been a lack of investigation
      into possible effects on executive function. In addition, only one study has
      investigated the effects of chronic treatment in young volunteers. OBJECTIVES:
      This study was conducted to compare the effects of ginkgo after acute and chronic
      treatment on tests of attention, memory and executive function in healthy
      university students. METHODS: Using a placebo-controlled double-blind design, in
      experiment 1, 52 students were randomly allocated to receive a single dose of
      ginkgo (120 mg, n=26) or placebo (n=26), and were tested 4 h later. In experiment
      2, 40 students were randomly allocated to receive ginkgo (120 mg/day; n=20) or
      placebo (n=20) for a 6-week period and were tested at baseline and after 6 weeks
      of treatment. In both experiments, participants underwent tests of sustained
      attention, episodic and working memory, mental flexibility and planning, and
      completed mood rating scales. RESULTS: The acute dose of ginkgo significantly
      improved performance on the sustained-attention task and pattern-recognition
      memory task; however, there were no effects on working memory, planning, mental
      flexibility or mood. After 6 weeks of treatment, there were no significant
      effects of ginkgo on mood or any of the cognitive tests. CONCLUSIONS: In line
      with the literature, after acute administration ginkgo improved performance in
      tests of attention and memory. However, there were no effects after 6 weeks,
      suggesting that tolerance develops to the effects in young, healthy participants.

PMID- 15739077
TI  - Sex differences in the escalation of oral phencyclidine (PCP) self-administration
      under FR and PR schedules in rhesus monkeys.
AB  - RATIONALE: Studies with male rats indicate that long access (LgA) vs short access
      (ShA) to i.v. cocaine and heroin self-administration leads to an escalation of
      drug intake and a subsequent upward shift of the dose-response function.
      OBJECTIVE: The purpose of this experiment was to extend these results to male and
      female rhesus monkeys and oral phencyclidine (PCP) self-administration under
      fixed-ratio (FR) and progressive-ratio (PR) schedules. METHODS: Adult rhesus
      monkeys (seven females and nine males) orally self-administered PCP (0.25 mg/ml)
      and water under concurrent FR 16 FR 16 schedules during daily ShA 3-h sessions.
      Since females weighed less than males, each liquid delivery (0.6 ml) represented
      a higher unit dose mg/kg for females than males, but drug concentration mg/ml
      remained constant. Concurrent PR PR schedules were then used to obtain a
      concentration-response function (0.125, 0.25, 0.5, and 1.0 mg/ml). Next, PCP and
      water were available during LgA 6-h sessions under concurrent FR 16 FR 16
      schedules for 21 days. The monkeys were then retested under the concurrent FR 16
      FR 16 and PR PR conditions during ShA sessions. RESULTS: Under the initial ShA
      concurrent FR 16 FR 16 schedules, females and males did not differ on PCP
      deliveries or intake (mg/kg); however, during LgA, males and females had more PCP
      deliveries compared with ShA. During LgA, males exceeded females in PCP
      deliveries, but females were higher than males in mg/kg PCP intake. Also, PCP
      (but not water) deliveries and mg/kg PCP intake significantly increased from the
      first 3 days to the last 3 days of the 21-day LgA period in both males and
      females. The subsequent ShA FR 16 FR 16 performance did not differ by sex, but it
      was significantly elevated above the first ShA period in both sexes. The
      concentration-response function for PCP break point under the PR PR schedules and
      PCP intake (mg/kg) were significantly shifted upward during the second (vs first)
      ShA period, and females' mg/kg intake significantly exceeded males'. CONCLUSIONS:
      Male and female rhesus monkeys both showed escalation of PCP self-administration
      during LgA to PCP and during ShA that occurred after (vs before) LgA. Both showed
      vertical upward shifts in the concentration x intake (mg/kg) function under the
      PR schedule, and females exceeded males on this measure. These findings with PCP
      and monkeys are consistent with vertical upward shifts of cocaine dose-response
      functions in previous escalation studies in male rats and reports of sex
      differences (F>M) during several other phases of drug abuse.

PMID- 15739078
TI  - Involvement of gamma-hydroxybutyrate (GHB) and GABA-B receptors in the acute
      behavioral effects of GHB in baboons.
AB  - RATIONALE: Gamma-hydroxybutyrate (GHB) is used for the treatment of narcolepsy,
      but it is also a drug of abuse. The behavioral pharmacology of GHB is not well
      defined. OBJECTIVES: The current study was conducted to characterize the
      behavioral effects of a range of GHB doses in baboons (N=4) and to evaluate
      whether a GABA-B receptor antagonist and a GHB receptor antagonist would block a
      behaviorally active dose of GHB. METHODS: In the first experiment, GHB (32-420
      mg/kg) or vehicle was administered via an intragastric catheter. Sixty min after
      dosing, subjects were presented with a fine-motor task and observed. Food pellets
      were available under a fixed-ratio schedule of reinforcement 20-h/day. In the
      second experiment, the GABA-B antagonist CGP36742 (10-56 mg/kg), the putative GHB
      antagonist NCS-382 (0.1-10 mg/kg), or vehicle were administered alone and then in
      combination with GHB (320 mg/kg). RESULTS: GHB dose-dependently decreased the
      number of food pellets earned. Performance in the motor task was also impaired
      and accompanied by signs of sedation and gastrointestinal discomfort.
      Pretreatment with CGP36742 antagonized GHB-induced suppression of food-maintained
      behavior and performance on the fine-motor task. Signs of abdominal discomfort,
      ataxia, and muscle relaxation produced by GHB were also reduced by pretreatment
      with CGP36742. In contrast, pretreatment with NCS-382 sometimes restored
      performance in the fine-motor task and increased food-maintained behavior, but
      the effect was variable across doses and baboons. Some doses of NCS-382 appeared
      to exacerbate ataxia and gastrointestinal discomfort produced by GHB in some
      subjects. CONCLUSIONS: These data indicate that while GABA-B receptors play a
      significant role in mediating the behavioral effects of GHB in baboon, the role
      of GHB receptors is less clear.

PMID- 15739080
TI  - Long-term follow-up in children with functional hemispherectomy for Rasmussen's
      encephalitis.
AB  - INTRODUCTION: Cerebral hemispherectomy has been performed for over 60 years.
      Multiple variations of functional hemispherectomy have been performed since its
      inception by Rasmussen. Long-term follow-up for these variations is lacking in
      the medical literature. METHODS: We review the long-term follow-up for five
      children with Rasmussen's encephalitis who underwent a modification of functional
      hemispherectomy. RESULTS: The length of follow-up for this cohort ranged from 13
      to 23 years (mean 15.6 years). All patients experienced immediate and complete
      elimination of seizures. Only one patient underwent ventriculoperitoneal shunt
      placement. All patients are capable of ambulating on their own. Many years
      following their procedures, this cohort of patients remains seizure free.

PMID- 15739079
TI  - Effects of chronic cocaine self-administration on norepinephrine transporters in
      the nonhuman primate brain.
AB  - RATIONALE: While cocaine blocks dopamine and serotonin transporters, considerably
      less emphasis has been placed on its effects following blockade of the
      norepinephrine transporter (NET). To date, no studies have made a systematic
      investigation of the effects of chronic cocaine on primate NET density.
      OBJECTIVE: We previously reported increases in NET density in portions of the
      monkey bed nucleus of stria terminalis after 100 days of cocaine self
      administration. In the present study we extend these findings and assess the
      changes in [3H]nisoxetine binding in additional brain regions of rhesus monkeys
      chronically self-administrating cocaine. RESULTS: [3H]Nisoxetine binding sites in
      the A1 noradrenergic cell group were significantly higher after 5 days of cocaine
      exposure. One hundred days of self-administration also induced a higher density
      of NET binding within the A1 cell group; however, in addition, the effects
      extended to the nucleus prepositus, as well as forebrain regions such as
      hypothalamic nuclei, basolateral amygdala, parasubiculum, and entorhinal cortex.
      CONCLUSIONS: These data demonstrate that cocaine self-administration alters the
      noradrenergic system of nonhuman primates. Although cocaine affected NET binding
      sites in the forebrain projections of both the ventral (VNAB) and dorsal (DNAB)
      noradrenergic bundles, the alteration in the A1 cell group at the early time
      point suggests that the VNAB appears to be more sensitive than the DNAB to the
      effects of cocaine. Given the role of norepinephrine in arousal and attention, as
      well as mediating responses to stress, long-term exposure to cocaine is likely to
      result in significant changes in the way in which information is perceived and
      processed by the central nervous system of long-term cocaine users.

PMID- 15739082
TI  - A case of solitary neurofibroma of the nasal dorsum: resection using an external
      rhinoplasty approach.
AB  - A 7-year-old girl had suffered from progressive swelling of the nasal dorsum over
      2 years. Computed tomography and magnetic resonance imaging showed a large soft
      tissue density in the nasal dorsum. Tc-99m DTPA cisternography and brain SPECT
      showed a restricted mass in the nasal dorsum without intracranial connection. The
      mass was resected using an external rhinoplasty approach, and the pathologic
      diagnosis was of neurofibroma. Furthermore, the nasal dorsum was identified as
      the origin of the neurofibroma without the stigma of neurofibromatosis. Here, we
      present this case and discuss the clinical and pathological aspects of
      neurofibroma arising in the nasal dorsum.

PMID- 15739081
TI  - Clinical and molecular prognostic factors in operable laryngeal cancer.
AB  - Many factors affect the prognosis in operable laryngeal squamous cell carcinoma
      (LSCC). Many clinical factors have been implicated in tumor recurrence and poor
      survival of the patients. The aim of the present study is to investigate the
      demographic, clinical and histological characteristics as prognostic factors.
      Moreover, our aim is to analyze the role of modern molecular biomarkers in the
      prognosis of patients with LSCC. One hundred patients with operable laryngeal
      carcinoma underwent surgery as primary treatment between April 1999 and April
      2002. Ninety-four of them were men and 6 women, with a median age of 62 years (39
      77). All demographic data of the patients were recorded. Staging of the tumor
      revealed 20 cases with T2 cancer, 46 cases with T3 and 34 cases with T4, while N
      classification included 91 patients with N0 tumor, 3 with N1 and 6 with N2. Among
      the 100 cases, 47 were located in the glottis, 46 in the supraglottic region and
      7 were transglottic. Histology grading revealed 35 cases of grade G1, 50 cases of
      G2 and 15 cases of G3. Postoperatively, all patients were followed regularly for
      the possibility of tumor relapse, with a median follow-up period of 40.2 months
      (4.8-58.4). During the operation, a tissue specimen was collected from the tumor.
      The specimens were used for RNA and DNA extraction. Isolated RNA was used to
      investigate the expression of wt-p53, bcl-2, VEGF and EGFR by the reverse
      transcriptase PCR method (RT-PCR) using specific primers, while genomic DNA was
      used for the detection of EBV and HPV (16/18 subtypes) by the consensus primer
      mediated polymerase chain reaction method (PCR). All data such as tumor
      recurrence and survival were recorded. Statistical analysis was performed using
      the SPSS and STATA statistical packages in order to investigate the role of all
      clinical and molecular factors and their combinations as significant prognostic
      markers. The tumor recurrence rate was 31%, while the tumor associated death rate
      was 27% and total death rate 30%. Univariate analysis for overall survival showed
      significance for the T stage, TNM stage and site of the tumor. Univariate
      analysis for the time to progression showed significance for the T stage, N
      stage, TNM stage, site of the tumor and tumors simultaneously positive for EGFR
      and VEGF, while EGFR expression was borderline insignificant. Multivariate
      analysis revealed TNM stage as the only significant factor for overall survival,
      and TNM stage, site of the tumor and EGFR expression as significant factors for
      time to progression. The molecular biomarkers EGFR and VEGF have a prognostic
      significance in laryngeal cancer in addition to the established clinical
      prognostic factors such as the stage and site of the tumor. These markers, apart
      from their role in carcinogenesis, seem to play an important role in tumor
      relapse.

PMID- 15739083
TI  - Stent-graft treatment of extracranial internal carotid artery aneurysm.
AB  - Extracranial internal carotid artery aneurysm is not a frequent finding. Although
      there are a number of methods used for the treatment of this kind of pathology,
      every approach should be tailored to the patient. The authors describe the case
      of a patient with a large extracranial internal carotid artery aneurysm
      presenting as a tumor of the parapharyngeal space, treated with a stent-graft.
      The patient remains asymptomatic at the 2-year follow-up. To our knowledge, this
      type of successful treatment of a carotid aneurysm has been reported only once so
      far.

PMID- 15739084
TI  - VEMP recording by binaural simultaneous stimulation in subjects with vestibulo
      cochlear disorders.
AB  - To reduce the testing time of vestibular evoked myogenic potentials (VEMP) and
      the physical efforts of subjects, we studied if VEMP recording by binaural
      simultaneous stimulation in patients with vestibulo-cochlear disorders can be
      applicable as a screening test. Twenty-eight patients with vestibulo-cochlear
      disorders (12 men and 16 women, 22 to 77 years of age) were enrolled in this
      study. Patients were presented with binaural or monaural click (95 dBnHL)
      stimulation to record VEMPs. Their VEMP responses to binaural simultaneous
      stimulation were compared with those of monaural individual stimulation. Twenty
      six of the 28 patients (93%) showed the same results in binaural simultaneous
      stimulation as in monaural individual stimulation. Amplitudes of p13-n23 to
      binaural simultaneous stimulation showed significant correlation to those of
      monaural individual stimulation ( r =0.774, P <0.0001 t -test). Peak latencies of
      p13 and n23 of binaural simultaneous stimulation also showed significant
      correlation to those of monaural individual stimulation (p13: r =0.684, P <0.0001
      t -test, n23: r =0.657, P <0.0001 t -test). The binaural simultaneous stimulation
      method for VEMP recording is applicable for patients with vestibulo-cochlear
      disorders as a screening test in the clinic.

PMID- 15739085
TI  - The chondroid syringoma: report of a case arising from the external auditory
      canal.
AB  - Chondroid syringoma is an uncommon, benign skin adnexal tumour. It usually
      presents as a slowly growing intradermal or subcutaneous nodule on the face.
      Treatment involves local excision with a cuff of normal tissue to prevent
      recurrence. A rare case of chondroid syringoma arising from the external auditory
      canal is reported. The clinical features, histology, treatment and follow-up are
      discussed.

PMID- 15739086
TI  - Management of epistaxis in hereditary hemorrhagic telangiectasia by Nd:YAG laser
      and quality of life assessment using the HR-QoL questionnaire.
AB  - The purpose of this study was to describe the results of Nd:YAG laser application
      in hereditary hemorrhagic telangiectasia (HHT) patients and to measure the Health
      Related Quality of Life (HR-QoL) in patients with HHT before and after Nd:YAG
      laser application in a prospective, clinical trial at a university hospital.
      Twenty-seven consecutive patients with HHT and mild to moderate degrees of
      epistaxis were followed-up for 2 years after Nd:YAG laser treatments. Recurrence
      of epistaxis after Nd:YAG laser application and measurement of HR-QoL using the
      International Quality of Life Assessment questionnaire, version 1.1 (IQOLA 1.1),
      was found. Eight patients (30%) received only one Nd:YAG laser treatment, 15
      (56%) had a recurrence and received a second treatment and 4 (14%) had two
      recurrences and received three Nd:YAG laser treatments. HR-QoL was improved 2
      years after the first Nd:YAG laser application in both its Physical Health
      Dimension (47.5+/-2.9 vs. 38.1+/-2.3 before treatment, P <0.05) and Mental Health
      Dimension (45.1+/-2.7 vs. 39.6+/-2.4 before treatment, P <0.05). Although no
      curative treatment for HHT exists, Nd:YAG laser treatment seems to constitute a
      simple and efficient method of epistaxis control, resulting in a significant
      improvement in quality of life.

PMID- 15739087
TI  - Angiofibroma: an outcome review of conventional surgical approaches.
AB  - Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor of the nasopharynx,
      and for its treatment, many surgical approaches have been recommended. However,
      selecting the appropriate one for the tumor in an advanced stage is still
      controversial. In this study, we evaluate the rate of recurrence of JNA and its
      relationship to the preoperative stage as well as various surgical approaches.
      Thirty-seven patients with pathologically proven JNA were retrospectively
      analyzed. For each patient, data were obtained regarding the primary extension,
      various surgical approaches and rate of recurrence. Seven patients were in stage
      III with intracranial extensions. Two of these patients had symptomatic
      recurrence that needed surgery. Three of them were disease free, and in two cases
      residues were demonstrated that were asymptomatic and were chosen only to be
      observed. Among different surgical approaches used, the transpalatal resulted in
      1 recurrence out of 14 patients treated with this approach when the lesion was
      limited to the nasal cavity, nasopharynx and paranasal sinuses (stage I). No
      recurrence was observed with the use of this approach with lesions with minimal
      extension to the pterygopalatine fossa (stage IIA). But among three patients with
      intracranial extension who were treated with this approach, two resulted in
      symptomatic recurrence; however, using the Lefort I surgical technique, no
      evidence of recurrence was observed in the two patients in stage III who were
      treated with this approach. Involvement of the orbit, middle cranial fossa and
      base of the pterygoid by the primary JNA results in a higher incident of
      recurrent tumor. Among different surgical techniques, the lowest recurrence rate
      is seen either in the transpalatal approach when the tumor is limited to the
      nasopharynx with extension to the nasal cavity or paranasal sinuses or with the
      Lefort I approach when skull base invasion is present.

PMID- 15739088
TI  - Automatic speaking valve in speech rehabilitation for laryngectomized patients.
AB  - For speech rehabilitation after total laryngectomy, the Provox FreeHands Heat and
      Moisture Exchanger (FreeHands HME; Atos Medical AB, Horby, Sweden) was compared
      with the Provox Heat and Moisture Exchanger (HME), and the patients' Health
      Related Quality of Life (HRQoL) was assessed. A review of the English literature
      was performed considering automatic speaking valves. The study design was a
      cohort study. Fourteen laryngectomized male patients who had used the HME
      successfully before receiving the FreeHands HME entered the study. An ENT
      specialist and a speech pathologist examined these patients. Data concerning
      voicing, breathing, skin adhesion, voice and speech quality, and HRQoL were
      collected by a structured questionnaire. Voice recordings were performed for
      evaluation of the quality of the voice. A computer-aided search of the MED-LINE
      database was conducted, supplemented by hand searches of key journals. Twelve
      patients had used the FreeHands HME on special social occasions and reported
      three main reasons why FreeHands HME was unsuitable for continuous use: heavier
      breathing, more difficult speaking, and worse subjective quality of voice. With
      HME, phonation time tended to be longer and the softest phonation softer ( P
      =0.034). The loudest phonation was louder with FreeHands HME ( P =0.015).
      Patients' HRQoL assessed by the 15D profile was similar to that of the age- and
      sex-matched male Finnish general population (patients 0.877, population 0.884). A
      review of the literature showed few works dealing with automatic speaking valves.
      The FreeHands HME is a useful additional device in a selected group of
      laryngectomized patients. Total laryngectomy did not lower patients' HRQoL
      notably.

PMID- 15739089
TI  - Prognostic value of telomerase and DNA ploidy in laryngeal carcinoma.
AB  - Prognosis of carcinoma of the larynx is currently based on the morphologic
      analysis of the tumor extent, differentiation grading and type of microscopic
      invasion. The DNA ploidy status and the cell proliferation activity may give
      complementary information about the prognosis. Telomerase may be used as a
      measure of tumor proliferation. The aim of this work was to investigate the
      probable application of telomerase as a measure of cell immortalization as well
      as DNA ploidy as a measure of cell proliferation in the prognosis of patients
      with laryngeal carcinoma. The work was carried out as a prospective observational
      study that included 35 patients with laryngeal carcinoma who were treated
      surgically at Ain Shams University Hospitals, Cairo, Egypt. Flowcytometric
      analysis and biochemical assay of telomerase using human Telomerase Reverse
      Transcriptase (hTERT) mRNA assay by RT-PCR in resected specimens were done. The
      proliferative indices in different parts of the tumor were found to be
      significantly different from each other, with those of tumor edges being the
      highest. The ploidy status at the edge of the tumor was significantly different
      between surviving and non-surviving patients, while the tumor core proliferative
      index was found to be significantly lower in patients without recurrence than
      those with recurrence. A gradient of telomerase levels was noticed, with levels
      from tumor cores being the highest followed by tumor edges, resection margins and
      the lowest levels in lymph nodes. Multivariate analysis showed hTERT levels in
      tumor edges to significantly affect survival. Both Flowcytometric parameters and
      telomerase activity may be useful as a prognostic factor for survival in patients
      with laryngeal carcinoma. Telomerase activity may be used for biologic
      demarcation for conservational laryngeal surgery, as well as a 'spectral' marker.

PMID- 15739090
TI  - Considerations of isolated destruction of the short process of the incus in a
      case of cholesteatoma.
AB  - Cholesteatoma occurs frequently with the destruction of the ossicles. The most
      commonly eroded ossicle has been reported to be the incus. Many studies report
      destruction of the long process and body of the incus. However, isolated erosion
      of the short process of the incus is an unusual finding. We present such a case
      with a slight conductive hearing loss that remained unchanged at 2 1/2 years
      postoperatively. The short process of the incus may contribute to hearing up to
      10-15 dB. It is also possible that it plays a role in epitympanic aeration by
      supplying an attachment surface to the incudal folds.

PMID- 15739091
TI  - [Influence of blockades with local anesthetics on the stimulation ability of a
      nerve by peripheral nerve stimulation. Results of a randomized study].
AB  - In the present study we examined the influence of local anesthetics on the
      ability to stimulate a nerve by means of peripheral nerve stimulation. In 35
      patients either 5 ml saline (group 1, n=18) or local anesthetics (group 2, n=17)
      were injected close to the sciatic nerve in a randomized and double-blind manner.
      The current needed to stimulate the nerve was measured 30 s and 2 min after
      injection. The results showed that 30 s and 2 min after injection of local
      anesthetics there is a strong local anesthetic effect. Therefore nerve damage
      might occur despite the use of peripheral nerve stimulation. Thus, the multiple
      injection technique in a close anatomical area has to be considered critically,
      because anesthetized or partially anesthetized nerves have a lower stimulating
      ability and could be damaged by a second or third puncture.

PMID- 15739092
TI  - [Intracranial haemorrhage. A reason for delayed awakening after general
      anaesthesia].
AB  - Delayed awakening after general anaesthesia is in the majority of cases due to
      prolonged effects of anaesthetic drugs. However, intracerebral processes are also
      associated with disturbances of consciousness. Here, we report a case of a female
      patient who developed an intracerebral haemorrhage because of an arteriovenous
      malformation during routine surgery. This shows that in the case of delayed
      awakening after general anaesthesia the possibility of an intracerebral process
      should be considered early even after routine surgery.

PMID- 15739093
TI  - The effect of citalopram hydrobromide on 5-HT2A receptors in the impulsive
      aggressive dog, as measured with 123I-5-I-R91150 SPECT.
AB  - PURPOSE: Involvement of the serotonergic system in impulsive aggression has been
      demonstrated in both human and animal studies. The purpose of the present study
      was to investigate the effect of citalopram hydrobromide (a selective serotonin
      re-uptake inhibitor) on the 5-HT(2A) receptor and brain perfusion in impulsive
      aggressive dogs by means of single-photon emission computed tomography. METHODS:
      The binding index of the radioligand (123)I-5-I-R91150 was measured before and
      after treatment with citalopram hydrobromide in nine impulsive-aggressive dogs.
      Regional perfusion was measured with (99m)Tc-ethyl cysteinate dimer (ECD).
      Behaviour was assessed before treatment and again after 6 weeks of treatment.
      RESULTS: A correlation was found between decreased binding and behavioural
      improvement in eight out of nine dogs. The 5-HT(2A) receptor binding index was
      significantly reduced after citalopram hydrobromide treatment in all cortical
      regions but not in the subcortical area. None of the dogs displayed alterations
      in perfusion on the post-treatment scans. CONCLUSION: This study supports
      previous findings regarding the involvement of the serotonergic system in
      impulsive aggression in dogs in general. More specifically, the effect of
      treatment on the 5-HT(2A) receptor binding index could be demonstrated and the
      decreased binding index correlated with behavioural improvement.

PMID- 15739094
TI  - Risk of contact allergy and dermatitis at a wind turbine plant using epoxy resin
      based plastics.
AB  - AIMS: To identify workplace and individual risk factors for occupational contact
      allergy and dermatitis. METHODS: A cross-sectional study was carried out at an
      international company producing wind turbine systems in Denmark. A cohort of 724
      production workers at four facilities was highly exposed to epoxy resin as well
      as other chemicals. A screening questionnaire (participation rate 84.7%) was
      followed by an interview by an occupational physician and a dermatological
      examination, including patch testing, for a comprehensive list of potential
      workplace sensitizers. RESULTS: Clinically diagnosed dermatitis was found among
      214 workers (35.8%) and contact allergy to materials used in the workplace was
      found in 66 workers (10.9% of the total population and 20.3% of those who
      underwent patch testing). Of the 66 workers with a work-related allergy, 40
      (60.6%) were allergic to epoxy compounds, 25 (37.9%) to hardeners and ten (15.2%)
      to other workplace materials, where one person showed an allergy only to these
      materials. Experiencing contact allergy was related to older age and longer
      employment in the workplace-however, neither of these risk factors was
      significant. The main risk factor for current dermatitis was contact allergy to
      materials used in the workplace, determined by patch testing, OR=5.4 (95% CI 3.9
      9.9). Fewer days of absence from work was also related to current dermatitis,
      OR=2.0 (95% CI 1.2-3.5). CONCLUSIONS: In a cohort of workers with extensive
      exposure to chemicals related to epoxy-resin systems, contact dermatitis and
      allergy was prevalent. Older age and longer duration of employment at the
      workplace were individual risk factors for allergy to workplace materials, whilst
      work-related allergies and longer duration of employment at the workplace were
      significant risk factors for current dermatitis.

PMID- 15739095
TI  - Molecular mechanisms of ginsenoside Rh2-mediated G1 growth arrest and apoptosis
      in human lung adenocarcinoma A549 cells.
AB  - Ginsenoside Rh2 (Rh2), a purified ginseng saponin, has been shown to have
      antiproliferative effects in certain cancer cell types. However, the molecular
      mechanisms of Rh2 on cell growth and death have not been fully clarified. In this
      study, the antiproliferative effect of Rh2 in human lung adenocarcinoma A549
      cells was investigated. Treatment of A549 cells with 30 mug/ml Rh2 resulted in
      G(1) phase arrest, followed by progression to apoptosis. This Rh2-mediated G(1)
      arrest was accompanied by downregulation of the protein levels and kinase
      activities of cyclin-D1, cyclin-E and Cdk6, and the upregulation of pRb2/p130. In
      addition, Rh2-induced apoptosis was confirmed by TUNEL assay and DNA
      fragmentation analysis. Administration of Rh2 caused an increase in the
      expression levels of TRAIL-RI (DR4) death receptor but did not alter the levels
      of other death receptors or Bcl-2 family molecules. Furthermore, the Rh2-induced
      apoptosis was significantly inhibited by DR4:Fc fusion protein, which inhibits
      TRAIL-DR4-mediated apoptosis. In addition, caspase-2, caspase-3 and caspase-8
      were highly activated upon Rh2 treatment. Inhibitors of caspase-2, caspase-3 and
      caspase-8 markedly prevented the cell death induced by Rh2. Inhibitor of caspase
      8 significantly inhibited the activation of caspase-2, caspase-3 and caspase-8.
      These observations indicate that multiple G(1)-related cell cycle regulatory
      proteins are regulated by Rh2 and contribute to Rh2-induced G(1) growth arrest.
      The increase in the expression level of DR4 death receptor may play a critical
      role in the initiation of Rh2-triggered apoptosis, and the activation of the
      caspase-8/caspase-3 cascade acts as the executioner of the Rh2-induced death
      process.

PMID- 15739096
TI  - Endothelial functions in Behcet's disease.
AB  - Behcet's disease (BD) is a systemic vasculitis, capable of involving all types of
      vessels. Endothelial dysfunction (ED) has been previously documented in BD. The
      aim of the study was to see whether ED was more prominent in Behcet's patients
      with vascular involvement (VI) than in those without. The study population
      consisted of 65 patients with BD, 27 of whom had VI, and 30 healthy controls.
      High-resolution ultrasound was used to measure endothelium-dependent
      vasodilatation (EDVD) of brachial artery. Overall, regardless of VI, EDVD was
      significantly impaired in patients with BD compared with controls (11.4 +/- 6.3
      vs 20.4 +/- 9.1%,P = 0.001); however, EDVD was similar in BD patients with and
      without VI (9.7 +/- 6.3% vs 12.6 +/- 6.1%, P = 0.07). Patients with BD had
      significantly-higher plasma homocysteine levels than controls (13 +/- 6
      micromol/L vs 9 +/- 3 micromol/L, P = 0.001). Plasma homocysteine levels were
      significantly higher in the subgroup with VI than in those without (15 +/- 7
      micromol/L vs 12 +/- 4 micromol/L, P = 0.03); however, we found no
      positive/significant correlation between plasma homocysteine levels and EDVD. ED
      is a constant feature of BD, regardless of VI. Etiology of ED in BD is probably
      multifactorial, including high homocysteine levels. As both ED and elevated
      homocysteine levels may represent an early atherosclerotic process, a more
      structured approach to risk factor assessment is needed in BD.

PMID- 15739097
TI  - Cartilage oligomeric matrix protein in serum in systemic lupus erythematosus and
      knee osteoarthritis. Preliminary communication.
AB  - The cartilage oligomeric matrix protein (COMP) is a glycoprotein, which occurs
      mainly in an articular cartilage. The amount of this protein increases under the
      influence of cytokines and growth factors. As a result of various diseases that
      cause damage to cartilage, fragments of matrix protein are released into synovial
      fluid and then into blood. The assessment of matrix protein level in serum, for
      example COMP, permits the establishment of the degree of cartilage damage in
      inflammatory joint diseases, and permits observation of the effectiveness of the
      treatment. Blood was collected from 30 systemic lupus erythematosus (SLE)
      patients, and from 30 patients with knee osteoarthritis (OA) who constituted the
      control group. Serum COMP level was determined using an inhibition enzyme-linked
      immunosorbent assay (ELISA). The average value of the serum COMP level in SLE
      patients was 11.3+/-3.7 U/l. According to correlation coefficients, serum COMP
      level is independent of patients' age, disease duration and the clinical picture
      of SLE. No correlation was found between serum COMP level and bone mass density
      (BMD) changes. In SLE patients with decreased haemoglobin levels (<11.0 g/dl)
      values compared with patients with normal haemoglobin level, the serum COMP level
      was observed to be significantly higher (P<0.05). Both in SLE patients with
      erythrocyte sedimentation rate (ESR) values over 60 mm/h and in patients with ESR
      values below 60 mm/h, the serum COMP level was observed to be significantly
      higher (P<0.05). A significant positive correlation was found between serum COMP
      level and ESR value, as well as a number of thrombocytes. Negative correlation
      occurred between the serum COMP level and the value of haemoglobin. The average
      value of COMP in OA patients was 10.4+/-2.7 U/l. No correlation was found between
      serum COMP level and patients' age and disease duration. There was correlation
      between the serum COMP level and the T-score value of densitometry examinations
      in OA patients. No statistical differences were found between the average serum
      COMP levels for SLE and OA patients.

PMID- 15739099
TI  - Interneuron deficits in patients with the Miller-Dieker syndrome.
AB  - Lissencephaly is characterized by a thickened cortex and loss of gyri, resulting
      in the brain having a smooth surface. Patients with lissencephaly frequently
      exhibit epilepsy and mental retardation, conditions often associated with a
      defect in inhibitory neurons. While lissencephaly has traditionally been
      considered a disorder of radial migration, recent data indicate interneurons
      migrate non-radially, while projection neurons migrate radially. To determine if
      an interneuron defect, and therefore a non-radial migration defect, exists in
      patients with lissencephaly, we studied the calretinin-expressing interneuron
      subpopulation in the brains from two fetuses and two children with lissencephaly
      and a deletion involving 17p13 deletion (Miller-Dieker syndrome) along with age
      matched controls. Our data indicate fetuses with the Miller-Dieker syndrome have
      a significant (tenfold) reduction in the number of calretinin-expressing
      interneurons present, whereas minimal reductions in the number of calretinin
      expressing interneurons are present in children with this disorder. These data
      parallel those seen in the Lis1(+/-) mouse model of human lissencephaly, and are
      consistent with a non-radial cell migration defect in humans. Thus, when
      considering the pathogenesis of human lissencephaly and the clinical
      manifestations in these patients, defects in both non-radial cell migration
      (inhibitory interneurons) and radial migration (excitatory projection neurons)
      must be considered.

PMID- 15739098
TI  - Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune
      restoration in AIDS-related progressive multifocal leukoencephalopathy.
AB  - HAART-induced immune restoration is beneficial for patients with AIDS-related
      progressive multifocal leukoencephalopathy (PML). However, in rare instances, an
      immune-reconstitution inflammatory syndrome (IRIS) may cause paradoxical clinical
      deterioration. We report the neuropathological study of an AIDS patient who
      presented with progressive cognitive deterioration; CD4(+) count was 117 and the
      HIV viral load >10(4); imaging showed non-enhancing lesions consistent with PML.
      Following initiation of HAART, CD4(+) was 300 and HIV viral load <10(3), but his
      neurological symptoms continued to deteriorate. Imaging revealed an increase in
      the size and number of lesions and enhancement of all the lesions. A stereotactic
      biopsy showed severe inflammatory and demyelinating lesions with marked
      infiltration by macrophages and T lymphocytes in the absence of a detectable
      infectious agent. Despite high doses of steroids, the patient died 3 months after
      admission. Autopsy showed two types of lesions: (1) active inflammatory PML
      changes with abundant JC virus, and intraparenchymal and perivascular
      infiltration by T lymphocytes, and (2) acute perivenous leukoencephalitis devoid
      of JC virus. Most lymphocytes were CD8(+) lymphocytes; CD4(+) lymphocytes were
      virtually absent. Two pathological reactions were associated with the paradoxical
      clinical deterioration related to dysregulation of the immune response
      characteristic of IRIS in PML: (1) an accentuation of JCV infection, and (2) a
      nonspecific acute perivenous leukoencephalitis. We suggest that both these types
      of lesions are due to an imbalance of CD8(+)/CD4(+) T cells, with massive
      infiltration of the cerebral parenchyma by CD8(+) cytotoxic T lymphocytes in the
      absence of sufficient CD4(+) response. Better understanding of the mechanisms of
      the IRIS may enable prevention or cure of this severe, sometimes fatal
      complication of HAART.

PMID- 15739100
TI  - Creutzfeldt-Jakob disease in a patient with an R208H mutation of the prion
      protein gene (PRNP) and a 17-kDa prion protein fragment.
AB  - A case of Creutzfeldt-Jakob disease (CJD) with a rare mutation of the prion
      protein (PrP) gene (PRNP) at codon 208 (R208H) is described. By comparison with
      two preceding reports, the case described here displayed two distinct biochemical
      and neuropathological features. Western blot analysis of brain homogenates
      showed, in addition to the commonly observed three bands of abnormal protease
      resistant PrP isoform (PrP(Sc)), an additional band of about 17 kDa.
      Neuropathological examination of the post mortem brain revealed tau pathology in
      the hippocampus and entorhinal cortex, as well as ballooned neurons in the
      cortex, hippocampus and subcortical gray matter.

PMID- 15739101
TI  - Losses of chromosomes 1p and 19q are rare in pediatric oligodendrogliomas.
AB  - Pediatric oligodendrogliomas are rare neoplasms and have not been characterized
      extensively either pathologically or genetically. Given the recent interest in
      the significance of chromosomal losses in predicting the clinical course and in
      establishing uniform diagnoses of adult oligodendrogliomas, we reviewed the
      pathological and clinical features of a series of pediatric oligodendrogliomas
      and determined their 1p and 19q status using fluorescence in situ hybridization.
      Of 19 tumors originally diagnosed as oligodendroglioma, 7 were oligodendroglioma,
      3 were anaplastic oligodendroglioma, 3 were oligoastrocytoma, and 6 were
      reclassified. Only one tumor, an anaplastic oligodendroglioma, had 1p loss; none
      had 19q loss. The single patient whose tumor had 1p loss did not have a
      particularly favorable clinical course. These results suggest that pediatric
      oligodendrogliomas arise by molecular alterations distinct from adult
      oligodendrogliomas, and such molecular alterations do not hold immediate promise
      as an adjunct to the diagnosis of pediatric oligodendrogliomas.

PMID- 15739102
TI  - Preparative synthesis of drug metabolites using human cytochrome P450s 3A4, 2C9
      and 1A2 with NADPH-P450 reductase expressed in Escherichia coli.
AB  - Three human cytochrome P450s, 3A4, 2C9 and 1A2, were each co-expressed with NADPH
      P450 reductase in Escherichia coli and used in the preparative synthesis of drug
      metabolites. Low dissolved oxygen (DO) concentration (<1%) during expression was
      found to be critical for producing active P450s. Control of temperature, pH and
      glycerol supplementation in 10-L fermentations enhanced enzyme expression 31-86%.
      Additional improvements were obtained by altering media formulations, resulting
      in bicistronic expression levels of 890, 1,800 and 1,010 nmol/L for 3A4, 2C9 and
      1A2, respectively. The P450 titers achieved in fermentors exceeded those in flask
      fermentations by 3- to 6-fold in this study and up to 10-fold when compared with
      previously reported literature. Intact cells and isolated membranes obtained from
      10-L fermentations were used to establish an efficient bioconversion system for
      the generation of metabolites. To demonstrate the utility of this approach, known
      metabolites of the anabolic steroid testosterone, the anti-inflammatory agent
      diclofenac and the analgesic agent phenacetin, were generated using 3A4, 2C9 and
      1A2, respectively. The reaction conditions were optimized for pH, temperature, DO
      concentration, use of co-solvent and glucose supplementation. Conversion yields
      of 29-93% were obtained from 1-L reactions, enabling isolation of 59 mg 6beta
      hydroxytestosterone, 110 mg 4'-hydroxydiclofenac and 88 mg acetaminophen.

PMID- 15739103
TI  - Nitrile bioconversion by Microbacterium imperiale CBS 498-74 resting cells in
      batch and ultrafiltration membrane bioreactors.
AB  - The biohydration of acrylonitrile, propionitrile and benzonitrile catalysed by
      the NHase activity contained in resting cells of Microbacterium imperiale CBS 498
      74 was operated at 5, 10 and 20 degrees C in laboratory-scale batch and membrane
      bioreactors. The bioreactions were conducted in buffered medium (50 mM
      Na(2)HPO(4)/NaH(2)PO(4), pH 7.0) in the presence of distilled water or tap-water,
      to simulate a possible end-pipe biotreatment process. The integral bioreactor
      performances were studied with a cell loading (dry cell weight; DCW) varying from
      0.1 mg(DCW) per reactor to 16 mg(DCW) per reactor, in order to realize near 100%
      bioconversion of acrylonitrile, propionitrile and benzonitrile without consistent
      loss of NHase activity.

PMID- 15739104
TI  - The 2-His-1-carboxylate facial triad: a versatile platform for dioxygen
      activation by mononuclear non-heme iron(II) enzymes.
AB  - General knowledge of dioxygen-activating mononuclear non-heme iron(II) enzymes
      containing a 2-His-1-carboxylate facial triad has significantly expanded in the
      last few years, due in large part to the extensive library of crystal structures
      that is now available. The common structural motif utilized by this enzyme
      superfamily acts as a platform upon which a wide assortment of substrate
      transformations are catalyzed. The facial triad binds a divalent metal ion at the
      active site, which leaves the opposite face of the octahedron available to
      coordinate a variety of exogenous ligands. The binding of substrate activates the
      metal center for attack by dioxygen, which is subsequently converted to a high
      valent iron intermediate, a formidable oxidizing species. Herein, we summarize
      crystallographic and mechanistic features of this metalloenzyme superfamily,
      which has enabled the proposal of a common but flexible pathway for dioxygen
      activation.

PMID- 15739106
TI  - Atypical Meigs' syndrome in a neonate with ovarian torsion associated with an
      ovarian dermoid cyst.
AB  - We describe a female neonate with ovarian torsion, ovarian follicular and dermoid
      cysts, congenital ascites, pleural effusions, and respiratory distress. Her
      symptoms were consistent with atypical Meigs' syndrome and resolved after
      unilateral oophorectomy. This is the first report in a neonate of this syndrome
      in association with congenital ovarian disease.

PMID- 15739105
TI  - Newer antidepressants: evaluation of fatal toxicity index and interaction with
      alcohol based on Finnish postmortem data.
AB  - Finnish postmortem toxicology data from 1995 to 2002 was analyzed to obtain
      improved estimates of fatal toxicity indices for the newer antidepressants and to
      evaluate their interaction with alcohol. Altogether 284 fatal poisonings were
      attributed to 12 different newer antidepressants. Venlafaxine, mianserin,
      moclobemide, and mirtazapine were responsible for significantly more deaths than
      expected from their sales. Their fatal toxicity indices were higher than those of
      selective serotonin reuptake inhibitors (SSRIs) but lower than those of tricyclic
      antidepressants. In fatal poisonings involving alcohol in combination with
      venlafaxine, mianserin, moclobemide, or mirtazapine, the median blood alcohol
      concentration (BAC) ranged from 2.35 to 2.7 mg/g, whereas in those involving
      alcohol in combination with citalopram or fluoxetine the median BAC was 2.9 and
      3.4 mg/g, respectively. The BAC was significantly lower in venlafaxine-related
      deaths than in those involving fluoxetine or citalopram. We conclude that among
      the newer antidepressants differences are present both in toxicity and in
      interaction potential with alcohol. The SSRIs appear to present a low risk of
      fatal poisoning when taken alone or in combination with alcohol, whereas
      venlafaxine is associated with an elevated risk.

PMID- 15739107
TI  - Intraoperative evaluation of bone decompression in anterior cervical spine
      surgery by three-dimensional fluoroscopy.
AB  - Sufficient bone decompression of osteophytes is essential for functional long
      term outcome in surgery for spondylotic cervical myelopathy. Postoperative CT
      scans clearly show that decompression is sometimes insufficient. Intraoperative
      CT scanning has been used to monitor sufficient decompression. Instead of
      standard intraoperative fluoroscopy, we used an isocentered three-dimensional
      (3D) fluoroscopy with 3D image reconstruction to evaluate the extent of bone
      decompression. From October 2003 to April 2004, we have used intraoperative 3D
      fluoroscopy on seven patients with anterior cervical spine surgery due to
      cervical spondylotic myelopathy. Five patients were operated on in one level, two
      patients had surgery in two segments. If surgery was performed in two levels or
      preoperative cinetic MRT showed cervical instability, internal plate fixation was
      done additionally. All patients were positioned on a radiolucent operating table,
      made of carbon fibers. Three-dimensional fluoroscopy was always performed before
      wound closure to evaluate sufficient bone removal. The scanning time was 120 s
      and the whole procedure from scanning to evaluation is approximately 5 min. In
      all patients we were able to evaluate the extent of bone decompression.
      Additionally, placement of cage, plates and screws can be evaluated
      intraoperatively. In one patient, 3D fluoroscopy showed insufficient
      decompression, especially on the right side. Further bone removal was performed
      before the end of the procedure. Intraoperative 3D fluoroscopy is a valuable tool
      for imaging bone decompression and implant location in anterior cervical spine
      surgery. The technique is safe, reliable and should help us to avoid incomplete
      decompression or misplacement of implants and therefore improve long-term
      functional outcome in cervical spine surgery in the future.

PMID- 15739108
TI  - Fusion as treatment for chronic low back pain--existing evidence, the scientific
      frontier and research strategies.

PMID- 15739109
TI  - Low bacterial count urinary tract infections in infants and young children.
AB  - The purpose of the study was to compare bacterial species, clinical, laboratory
      and imaging findings ((99m )Tc-dimercaptosuccinic acid renal scan and voiding
      cystogram) in infants and children with high (>/=10(5) colony forming units
      (CFU)/ml, group A patients) and low (</=5 x 10(4) CFU/ml, group C patients)
      bacterial count in urine cultures during first episode of urinary tract
      infection. Group B included patients with intermediate CFU/ml. Included were 419
      symptomatic patients with: (a) no previous antibiotic treatment, (b) urine
      samples for quantitative cultures taken by bladder catheterisation or suprapubic
      bladder aspiration, (c) growth of only one microorganism, and (d) age </=54
      months (age of the oldest patient of group C). Out of 419 cultures, Escherichia
      coli grew in 315 (75.2%), gram-negative bacteria except E. coli in 91 (21.7%) and
      gram-positive in 13 (3.1%). Group C patients were significantly ( P <0.0001) more
      often affected with gram-negative pathogens except E. coli than group A patients
      (21/44 versus 67/360). Most of group C patients were younger than 24 months of
      age; none was older than 54 months. Comparison of the prevalence of clinical and
      laboratory (leucocyte count, CRP, ESR) findings between groups A and C showed no
      significant differences. There was no statistically significant difference in the
      prevalence of pyelonephritis, reflux and urological malformations (except reflux)
      between groups A and C. CONCLUSION: Low bacterial count urinary tract infections
      mainly affect infants and young children and are often due to gram-negative
      bacteria other than E. coli. Clinical and laboratory findings, prevalence of
      pyelonephritis, reflux and urological malformations are similar in high and low
      bacterial count urinary tract infections.

PMID- 15739110
TI  - A central back-coupling hypothesis on the organization of motor synergies: a
      physical metaphor and a neural model.
AB  - We offer a hypothesis on the organization of multi-effector motor synergies and
      illustrate it with the task of force production with a set of fingers. A physical
      metaphor, a leaking bucket, is analyzed to demonstrate that an inanimate
      structure can show apparent error compensation among its elements. A neural model
      is developed using tunable back-coupling loops as means of assuring error
      compensation in a task-specific way. The model demonstrates non-trivial features
      of multi-finger interaction such as delayed emergence of force stabilizing
      synergies and simultaneous stabilization of the total force and total moment
      produced by the fingers. The hypothesis suggests that neurophysiological
      structures involving short-latency feedback may play a central role in the
      formation of motor synergies.

PMID- 15739111
TI  - The physical basis of alpha waves in the electroencephalogram and the origin of
      the "Berger effect".
AB  - Synchronised activity, differing in phase in different populations of neurons,
      plays an important role in existing theories on the function of brain
      oscillations (e.g., temporal correlation hypothesis). A prerequisite for this
      synchronisation is that stimuli are capable of affecting (resetting) the phase of
      brain oscillations. Such a change in the phase of brain waves is also assumed to
      underlie the "Berger effect": when observers open their eyes, the amplitude of
      EEG oscillations in the alpha band (8-13 Hz) decreases significantly. This
      finding is usually thought to involve a desynchronisation of activity in
      different neurons. For functional interpretations of brain oscillations in the
      visual system, it therefore seems to be crucial to find out whether or not the
      phase of brain oscillations can be affected by visual stimuli. To answer this
      question, we investigated whether alpha waves are generated by a linear or a
      nonlinear mechanism. If the mechanism is linear - in contrast to nonlinear ones -
      phases cannot be reset by a stimulus. It is shown that alpha-wave activity in the
      EEG comprises both linear and nonlinear components. The generation of alpha waves
      basically is a linear process and flash-evoked potentials are superimposed on
      ongoing alpha waves without resetting their phase. One nonlinear component is due
      to light adaptation, which contributes to the Berger effect. The results call
      into question theories about brain-wave function based on temporal correlation or
      event-related desynchronisation.

PMID- 15739113
TI  - PEDRAP: a new training alternative for pediatric radiologists.

PMID- 15739112
TI  - Use of a microbubble agent to increase the effects of high intensity focused
      ultrasound on liver tissue.
AB  - In order to find out whether high intensity focused ultrasound (HIFU) might be
      useful against hepatocellular carcinoma, we analyzed the effect of a microbubble
      agent (Levovist) on the temperature rise and tissue necrosis induced by HIFU.
      Rabbits were given 7 ml Levovist (300 mg/ml) or saline intravenously. Up to six
      areas per rabbit liver were exposed to HIFU for 60 s (2.18 MHz, I(SPTA)=400
      W/cm(2)). The volume of the tissue coagulated by HIFU was measured 10 min after
      the start of HIFU. HIFU-induced lesions were larger in the animals given
      Levovist: (mm(3), Levovist versus saline) 371+/-104 versus 166+/-71 (P<0.001).
      Temperatures in the animals given Levovist were also higher 60 s after the start
      of exposure: ( degrees C, Levovist versus saline) 20.3+/-3.5 versus 13.2+/-3.8
      (P<0.001). The amount of damage differed greatly, but the pathological changes
      caused by HIFU with Levovist were the same as those caused by HIFU with saline.
      Hemorrhagic areas and implosion cysts were seen, and many cells had been
      disrupted or destroyed. Microbubble agents developed for diagnostic uses could
      also be used in anticancer therapy.

PMID- 15739114
TI  - Unexplained mental retardation: is brain MRI useful?
AB  - BACKGROUND: Mental retardation (MR), defined as an IQ below 70, is a frequent
      cause of consultation in paediatrics. OBJECTIVE: To evaluate the yield of brain
      MRI in the diagnostic work-up of unexplained MR in children. PATIENTS AND
      METHODS: The MRI features and clinical data of 100 patients (age 1-18 years)
      affected with non-progressive MR of unknown origin were compared to an age
      matched control group (n=100). Two radiologists conducted an independent review
      of the MRI scans. RESULTS: Univariate and multivariate analyses showed a higher
      incidence of brain anomalies in the MR group than in the control group (53 vs 17,
      OR=5.7 [2.9-11.1]), for signal abnormalities within the periventricular white
      matter (OR=20.3 [2.6-155.3]), lateral ventricular dilatation (OR=15.6 [2.0-124]),
      mild corpus callosum abnormalities (shortness, atrophy) (OR=6.8 [1.8-25.6]) and
      subtle cerebellar abnormalities, including fissure enlargement (OR=5.2 [1.1
      26.2]). The diagnostic value of MRI abnormalities was considered good in 5% of
      patients (Alexander disease n=1, diffuse cortical malformation n=1, leukomalacia
      n=1, vermian agenesis n=1, commissural agenesis n=1), and weak in 48% of
      patients, in whom non-specific abnormalities did not lead to a diagnosis. Some
      clinical features resulted in a significantly higher percentage of abnormal MRI
      scans: abnormal neurological examination (82% vs 47%, P=0.008), abnormal skull
      circumference (66% vs 49%, P=0.04). Motor delay was associated with cerebellar
      abnormalities (P=0.01). CONCLUSIONS: This study confirms the weak diagnostic
      yield of MRI in mentally retarded children. The use of a control group has
      enabled us to identify the neuroimaging markers frequently associated with MR.
      Subgrouping patients according to neuroimaging markers and clinical signs should
      help identify those who would benefit from molecular studies.

PMID- 15739115
TI  - Delayed autoregulation of glucose transport in vascular endothelial cells.
AB  - AIMS/HYPOTHESIS: We aimed to characterise the development of autoregulation of
      glucose transport in vascular endothelial cells and its relationship to 12
      lipoxygenase (12-LO) expression. METHODS: Bovine aortic endothelial cells were
      exposed to 5.5 and 23.0 mmol/l glucose for up to 48 h. The rates of glucose
      transport, GLUT-1 and 12-LO expression and of 12-hydroxyeicosatetraenoic acid (12
      HETE) production were determined. RESULTS: We showed high glucose-dependent
      downregulation of glucose transport and transporter in vascular endothelial cells
      within 36-48 h. A similar time-dependent increase in the expression of 12-LO and
      the generation of its product 12-HETE was also observed. This downregulatory
      process was prevented when lipoxygenase activity was inhibited.
      CONCLUSIONS/INTERPRETATION: Vascular endothelial cells, which were previously
      thought to be "glucose-blind", do in fact downregulate GLUT-1 expression and the
      rate of glucose transport in response to extended exposure to high glucose
      concentrations. This slow development of glucose-induced downregulation in
      vascular endothelial cells is related to the slower basal rate of glucose
      transport in these cells and the slow induction of 12-LO. These data are
      interesting in view of current hypotheses that attribute vascular endothelial
      cell dysfunction in diabetes to the lack of a glucose-induced autoregulatory
      response.

PMID- 15739116
TI  - EEG abnormalities with and without relation to severe hypoglycaemia in
      adolescents with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: The aim of the present study was to identify whether adolescents
      with type 1 diabetes receiving modern multiple insulin injection therapy (MIT)
      have abnormal EEGs, and to elucidate possible correlations with a history of
      severe hypoglycaemia, poor metabolic control and nerve conduction defects.
      METHODS: We investigated 35 patients (age 14-19 years) with disease duration
      7.6+/-4.6 years, and 45 healthy control subjects. EEG spectral components were
      obtained from 15-min recordings in resting, awake subjects. Nerve conduction was
      measured bilaterally in motor and sensory fibres in the median, peroneal and
      sural nerves. RESULTS: The EEGs of patients showed an increase in slow activity
      (delta and theta) and a reduction in alpha peak frequency, both of which were
      most pronounced in the frontal regions (p<0.001). They also showed a decrease in
      fast activity, which was most pronounced bilaterally in the posterior temporal
      regions (alpha p<0.001, beta p<0.01, gamma p<0.001). A history of severe
      hypoglycaemia was correlated with a global increase in theta activity (p<0.01
      0.05). Poor metabolic control, measured as acute and long-term HbA1c levels, was
      correlated with an increase in delta activity and a decrease in alpha peak
      frequency. The decrease in fast activity in the temporal regions was a separate
      type of abnormality because it had a different distribution, and was not
      correlated with the increase in delta/theta power, poor metabolic control or with
      hypoglycaemia. CONCLUSIONS/INTERPRETATION: Recurrent severe hypoglycaemia and
      poor metabolic control are risk factors for EEG abnormalities in adolescents with
      type 1 diabetes receiving MIT treatment. In addition, we found pronounced
      abnormalities in the temporal regions that were not related to these risk
      factors.

PMID- 15739117
TI  - High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA
      levels in rat pancreatic islets without activating NFkappaB.
AB  - AIMS/HYPOTHESIS: Hyperglycaemia and the pro-inflammatory cytokine IL-1beta induce
      similar alterations of beta cell gene expression, including up-regulation of c
      Myc and haeme-oxygenase 1. These effects of hyperglycaemia may result from
      nuclear factor-kappa B (NFkappaB) activation by oxidative stress. To test this
      hypothesis, we compared the effects of IL-1beta, high glucose, and hydrogen
      peroxide, on NFkappaB DNA binding activity and target gene mRNA levels in
      cultured rat islets. METHODS: Rat islets were pre-cultured for 1 week in serum
      free RPMI medium containing 10 mmol/l glucose, and further cultured in glucose
      concentrations of 5-30 mmol/l plus various test substances. Islet NFkappaB
      activity was measured by ELISA and gene mRNA expression was measured by RT-PCR.
      RESULTS: IL-1beta consistently increased islet NFkappaB activity and c-Myc, haeme
      oxygenase 1, inducible nitric oxide synthase (iNOS), Fas, and inhibitor of
      NFkappaB alpha (IkappaBalpha) mRNA levels. In comparison, 1- to 7-day culture in
      30 mmol/l instead of 10 mmol/l glucose stimulated islet c-Myc and haeme-oxygenase
      1 expression without affecting NFkappaB activity or iNOS and IkappaBalpha mRNA
      levels. Fas mRNA levels only increased after 1 week in 30 mmol/l glucose.
      Overnight exposure to hydrogen peroxide mimicked the effects of 30 mmol/l glucose
      on haeme-oxygenase 1 and c-Myc mRNA levels without activating NFkappaB. On the
      other hand, the antioxidant N-acetyl-L-cysteine inhibited the stimulation of
      haeme-oxygenase 1 and c-Myc expression by 30 mmol/l glucose and/or hydrogen
      peroxide. CONCLUSIONS/INTERPRETATION: In contrast to IL-1beta, high glucose and
      hydrogen peroxide do not activate NFkappaB in cultured rat islets. It is
      suggested that the stimulation of islet c-Myc and haeme-oxygenase 1 expression by
      30 mmol/l glucose results from activation of a distinct, probably oxidative
      stress-dependent signalling pathway.

PMID- 15739118
TI  - A new drug carrier, Nalpha-deoxycholyl-L: -lysyl-methylester, for enhancing
      insulin absorption in the intestine.
AB  - AIMS/HYPOTHESIS: The development of an orally active insulin formulation will
      offer great advantages over conventional injectable insulin therapy in the
      treatment of patients with diabetes mellitus. Since insulin absorption in the
      intestine is restricted by the natural physiological characteristics of insulin,
      we developed a small synthetic compound, Nalpha-deoxycholyl-L: -lysyl-methylester
      (DCK), as an insulin carrier to enhance oral delivery. METHODS: Streptozotocin
      induced diabetic rats orally received single doses of insulin (42 U/kg) or
      insulin/DCK formulation (10, 21, 30 and 42 U/kg) under fasting conditions. Blood
      glucose levels and plasma insulin concentrations were measured for 6 h following
      the administration of the agents. An OGTT was also performed immediately after
      the administration of the oral insulin/DCK formulation. RESULTS: The
      administration of 21, 30 and 42 U/kg (based on insulin activity) of insulin/DCK
      formulation reduced plasma glucose levels by up to 33.0% (median; range 30.6
      70.2%), 78.5% (39.4-86.8%) and 75.2% (67.0-87.4%), respectively, compared with
      baseline levels. Furthermore, plasma insulin concentrations were observed to
      rapidly increase. In the OGTT, the insulin/DCK formulation reduced the AUC0-240
      for glucose by 30.8% (22.3-54.9%) (p<0.01), and stabilized glycaemia for up to 4
      h. CONCLUSIONS/INTERPRETATION: The results of this study demonstrate that the
      insulin/DCK formulation can be absorbed in the intestine and that it is
      biologically efficacious. We therefore suggest that this oral formulation could
      be used as an alternative to injectable insulin with enhanced clinical effects.

PMID- 15739119
TI  - A role for heterotrimeric GTP-binding proteins and ERK1/2 in insulin-mediated,
      nitric-oxide-dependent, cyclic GMP production in human umbilical vein endothelial
      cells.
AB  - AIMS/HYPOTHESIS: Insulin is known to stimulate endothelial nitric oxide
      synthesis, although much remains unknown about the intracellular mechanisms
      involved. This study aims to examine, in human endothelial cells, the specific
      contribution of heterotrimeric Gi proteins and extracellular signal-regulated
      protein kinases 1/2 (ERK1/2) in insulin signalling upstream of nitric-oxide
      dependent cyclic GMP production. METHODS: Human umbilical vein endothelial cells
      were treated with 1 nmol/l insulin in the presence or absence of inhibitors of
      tyrosine kinases (erbstatin), Gi proteins (pertussis toxin) or ERK1/2 (PD098059
      or U0126), and nitric oxide production was examined by quantification of
      intracellular cyclic GMP. Activation/phosphorylation of ERK1/2 by insulin was
      examined by immunoblotting with specific antibodies, and direct association of
      the insulin receptor with Gi proteins was examined by immunoprecipitation.
      RESULTS: Treatment of cells with a physiological concentration of insulin (1
      nmol/l) for 5 min increased nitric-oxide-dependent cyclic GMP accumulation by 3.3
      fold, and this was significantly inhibited by erbstatin. Insulin-stimulated
      cyclic GMP production was significantly reduced by pertussis toxin and by the
      inhibitors of ERK1/2, PD098059 and U0126. Immunoblotting indicated that insulin
      stimulated the phosphorylation of ERK1/2 after 5 min and 1 h, and that this was
      completely abolished by pertussis toxin, but insensitive to the nitric oxide
      synthase inhibitor L-NAME. No direct interaction of the insulin receptor beta
      with Gialpha2 could be demonstrated by immunoprecipitation.
      CONCLUSIONS/INTERPRETATION: This study demonstrates, for the first time, that
      nitric oxide production induced by physiologically relevant concentrations of
      insulin, is mediated by the post-receptor activation of a pertussis-sensitive GTP
      binding protein and subsequent downstream activation of the ERK1/2 cascade.

PMID- 15739121
TI  - Stress alters vascular-endothelial growth factor expression in rat arteries: role
      of nerve growth factor.
AB  - The aim of this study was to investigate the role of stress and nerve growth
      factor (NGF) on the expression of vascular-endothelial growth factor (VEGF) and
      NGF high-affinity receptor (tyrosine kinase A, TrKA) in the ascending and
      abdominal aorta.Adult male rats were exposed to immobilization stress for one
      hour or injected with purified murine NGF. Four hours after treatments, rats were
      sacrificed and VEGF, NGF and TrkA expression in ascending and abdominal aorta
      evaluated. The effects of anti-NGF treatment on arterial VEGF expression and on
      stress-induced arterial cell proliferation were also studied in control and
      stressed rats.The data indicated that both stress and NGF injection induced a
      rapid increase of arterial VEGF associated with an elevated level of NGF and TrkA
      in arterial tissues. Blocking NGF action by neutralizing NGF-antibodies, results
      in down-regulation of stress-induced VEGF expression by arteries and in the
      blockade of stress-induced proliferation of cells from the arterial wall.Overall
      our data demonstrated that NGF is involved in the regulation of VEGF and in
      cardiac vessels response after emotional stress.

PMID- 15739123
TI  - Plasma cathepsin D isoforms and their active metabolites increase after
      myocardial infarction and contribute to plasma renin activity.
AB  - Plasma renin activity (PRA) is often found to increase after myocardial
      infarction (MI). Elevated PRA may contribute to increased myocardial angiotensin
      II that is responsible for maladaptive remodeling of the myocardium after MI. We
      hypothesized that MI would also result in cardiac release of cathepsin D, a
      ubiquitous lysosomal enzyme with high renin sequence homology. Cathepsin D
      release from damaged myocardial tissue could contribute to angiotensin formation
      by acting as an enzymatic alternate to renin. We assessed circulating renin and
      cathepsin D from both control and MI patient plasma (7-20 hours after MI) using
      shallow gradient focusing that allowed for independent measurement of both
      enzymes. Cathepsin D was increased significantly in the plasma after MI (P <
      0.001). Furthermore, circulating active cathepsin D metabolites were also
      significantly elevated after MI (P < 0.04), and contained the majority of
      cathepsin D activity in plasma. Spiking control plasma with cathepsin D resulted
      in a variable but significant (P = 0.005) increase in PRA using a clinical assay.
      We conclude that 7-20 hours after MI, plasma cathepsin D is significantly
      elevated and most of the active enzymatic activity is circulating as plasma
      metabolites. Circulating cathepsin D can falsely increase clinical PRA
      determinations, and may also provide an alternative angiotensin formation pathway
      after MI.

PMID- 15739122
TI  - Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle
      cells.
AB  - Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and by
      obstructive changes of the pulmonary vasculature including smooth muscle cell
      proliferation which leads to medial hypertrophy and subsequent luminal narrowing.
      Sildenafil, an orally active inhibitor of cGMP phosphodiesterase-type-5, exerts
      pulmonary vasodilator activity in PAH patients. We evaluated the effects of
      sildenafil on growth of cultured human pulmonary artery smooth muscle cells
      (PASMC). The results indicate that sildenafil reduced DNA synthesis stimulated by
      PDGF and dose dependently inhibited PASMC proliferation. These effects were
      paralleled by a progressive increase in cGMP content, followed by an accumulation
      of cAMP. The treatment with 8-bromo-cGMP or dibutyryl-cAMP mimicked all the
      effects of sildenafil. On the other hand, treatment of PASMC with inhibitors of
      cGMP-dependent protein kinase (PKG) or cAMP-dependent protein kinase (PKA)
      reversed the antiproliferative effect of sildenafil. In addition, sildenafil
      inhibited the phosphorylation of ERK, a converging point for several pathways
      leading to cell proliferation. This effect was partially reduced by PKG
      inhibition and completely abolished by PKA inhibition.We conclude that sildenafil
      exerts an antiproliferative effect on human PASMC that is mediated by an
      interaction between the cGMP-PKG and the cAMP-PKA activated pathways, leading to
      inhibition of PDGF-mediated activation of the ERK.

PMID- 15739120
TI  - Pioglitazone elicits long-term improvements in insulin sensitivity in patients
      with type 2 diabetes: comparisons with gliclazide-based regimens.
AB  - AIMS/HYPOTHESIS: Recent studies have demonstrated that pioglitazone (PIO) has
      beneficial effects on insulin sensitivity compared with placebo in patients with
      type 2 diabetes. The effects of PIO and gliclazide (GLIC)-based therapy on
      insulin sensitivity have not previously been directly compared. This analysis
      aimed to compare the effects of 52 weeks of treatment with PIO (30-45 mg/day) and
      GLIC (80-320 mg/day), both titrated to maximum tolerable doses, as monotherapy or
      in combination with metformin (MET), on insulin sensitivity and lipid parameters
      known to be related to insulin sensitivity in patients with type 2 diabetes.
      METHODS: We performed an analysis of 1,880 patients with inadequately controlled
      type 2 diabetes (HbA1c 7.5-11.0%) who were participants in two parallel-group,
      double-blind, double-dummy, randomised, multicentre, clinical trials. Measures of
      insulin sensitivity and lipids were assessed. RESULTS: The PIO- and GLIC-based
      regimens produced similar levels of glycaemic control (HbA1c). In both trials,
      insulin sensitivity as assessed using the homeostasis model assessment was
      improved in patients receiving PIO, but decreased in those receiving GLIC (mean
      change, baseline to endpoint: PIO 15.5, GLIC -15.6; p<0.001 and PIO+MET 18.9,
      GLIC+MET -5.3; p<0.001). Improvements in the atherogenic index of plasma (mean
      change: PIO -0.17, GLIC -0.08; p<0.001 and PIO+MET -0.17, GLIC+MET -0.02;
      p<0.001), triglycerides (mean change, mmol/l: PIO+MET -0.62, GLIC+MET -0.22;
      p<0.001) and NEFA (mean change, mmol/l: PIO+MET -0.12, GLIC+MET-0.05; p<0.001)
      were greater in PIO-treated patients than in patients receiving GLIC.
      CONCLUSIONS/INTERPRETATION: The PIO-based regimens resulted in improved insulin
      sensitivity and more favourable insulin sensitivity-related lipid profiles
      compared with the GLIC-based regimens. These benefits may be important in the
      management of cardiovascular risk in patients with type 2 diabetes.

PMID- 15739124
TI  - Differential effects of isoflurane and ketamine/inactin anesthesia on cAMP and
      cardiac function in FVB/N mice during basal state and beta-adrenergic
      stimulation.
AB  - We evaluated the effect of the inhalant anesthetic isoflurane and the injectable
      combination of anesthetics ketamine/inactin on cardiac function by measuring left
      ventricular (LV) pressure in situ during control conditions and during beta
      adrenergic stimulation with isoproterenol (ISO). The control heart rate (HR) and
      the maximal rate of contraction were significantly higher in the isoflurane
      group, but there was no difference in the rate of relaxation. During the ISO
      (0.32 ng g body wt(-1) min(-1)) stimulation the developed pressure (DP) increased
      9.8 +/- 1.8% (n = 11) in the ketamine/inactin group and was unchanged in the
      isoflurane group. The HR increased 28.4 +/- 4.8% (n = 11) in the ketamine/inactin
      group and only 3.4 +/- 0.6% (n = 11) in the isoflurane group. The rate of
      contraction increased 103.2 +/- 9.3% (n = 11) and 13.6 +/- 4.6% (n = 11) in the
      ketamine/inactin and isoflurane groups, respectively. At this dose of ISO the
      rate of relaxation did not change significantly. In control conditions there was
      no difference in levels of cAMP between the groups (2.29 +/- 0.25 pmol/mg protein
      (n = 5) in the ketamine/inactin group and 2.79 +/- 0.35 pmol/mg protein (n = 6)
      in the isoflurane group). However, during the ISO stimulation the cAMP level
      increased only in the ketamine/ inactin group of animals (3.50 +/- 0.30 pmol/mg
      protein; n = 5). This level was significantly higher than the level in the
      isoflurane group stimulated with ISO (2.22 +/- 0.30 pmol/mg protein; n = 6). In
      summary, our results indicate that the anesthetics differ significantly in the
      extent of depression of the basal and beta-adrenergic stimulated state with the
      second messenger cAMP playing a prominent role.

PMID- 15739125
TI  - Four-year FM residency training.

PMID- 15739126
TI  - A comment on a comment.

PMID- 15739127
TI  - Assessing preclinical medical students' ability to communicate in writing.

PMID- 15739128
TI  - Learning to listen.

PMID- 15739130
TI  - A Web-based multimedia medical humanities curriculum.

PMID- 15739131
TI  - Educational research--to IRB, or not to IRB?

PMID- 15739132
TI  - Residency Review Committee for Family Medicine: an analysis of program citations.
AB  - BACKGROUND AND OBJECTIVES: The Residency Review Committee for Family Medicine
      (RRC-FM) is responsible for the accreditation of the nation's 474 residencies in
      family medicine. This analysis of RRC-FM actions was done to help residency
      directors and faculty better understand its operations and to provide a context
      for interpretation of its decisions. METHODS: All actions by the RRC-FM for the
      calendar year 2002 were reviewed and analyzed by program administrative format,
      accreditation actions, cycle length, and types of citations listed. RESULTS: Of
      the 117 core program reviews conducted, the most common programs were community
      based residencies with medical school affiliations. A total of 772 citations were
      issued, for an average of 6.6 citations per program. The average cycle length for
      reaccreditation was 3.5 years. No statistically significant (P<.05) variations in
      citation type, frequency, or cycle length by program type were demonstrated.
      Maternity care, family medicine center patient encounters, and gynecology
      curricula were the most common areas of noncompliance citations. CONCLUSIONS:
      Family medicine educators can use this information as benchmarks for program
      comparisons and to help identify areas for priority attention on both a local and
      a national basis. The effects of resident duty hours limitations and the
      implementation of the Accreditation Council for Graduate Medical Education
      Competencies are yet to be determined.

PMID- 15739133
TI  - The University of Tennessee's accelerated family medicine residency program 1992
      2002: an 11-year report.
AB  - BACKGROUND AND OBJECTIVES: In 1992, with the approval of the American Board of
      Family Medicine (ABFM) (formerly known as the American Board of Family Practice),
      we established an accelerated residency program (ARP) involving five residency
      programs at the University of Tennessee (UT). An accredited resident can complete
      medical school and residency in a combined total of 6 years. This paper is a
      report of our experience with the ARP. Our objective was to determine if
      accelerated residents performed as well as or better than non-accelerated
      residents. METHODS: Students are selected for the ARP on the basis of academic
      achievement, life experience, interviews, and commitment to family medicine. For
      the accelerated residents, we tracked outcomes measures, including medical school
      grade point average (GPA), US Medical Licensing Examination (USMLE) scores, ABFM
      In-training Examination scores, and board certification status. RESULTS: From
      1992 to 2002, 47 students entered the ARP at five UT residency programs. Five
      students did not complete the program. The average entering GPA was 3.17, and the
      average USMLE Step I score was 207. The accelerated residents, on average,
      performed better on ABFM In-training Examinations in the first and third years of
      residency than the non-accelerated residents did. Accelerated residents have a
      100% ABFM certification rate. A total of 76% practice in Tennessee, and 65% began
      practice in a rural county. CONCLUSIONS: The UT ARP has been an effective means
      for allowing medical students to complete their family medicine training in 6
      years. Accelerated residents have performed as well as or better than non
      accelerated residents on standardized testing.

PMID- 15739134
TI  - Assessing communication competence: a review of current tools.
AB  - BACKGROUND: The assessment of communication competence has become a major
      priority of medical educational, policy, and licensing organizations in the
      United States and Canada. Multiple tools are available to assess communication
      competence, but there are few studies that compare the tools. METHODS: A
      consensus panel of six family medicine educators evaluated 15 instruments
      measuring the physician-patient interview. The primary evaluation criteria came
      from the Kalamazoo Consensus Statement (KCS), which derived from a
      multidisciplinary panel of experts that defined seven essential elements of
      physician-patient communication. We evaluated psychometric properties of the
      instruments and other assessment criteria felt to be important to family
      physicians (exploring family issues, interview efficiency, and
      usability/practicality). RESULTS: Instruments that received the highest ratings
      on KCS elements were designed for faculty raters and varied in their
      practicality/usability ratings and psychometric properties. Few instruments were
      rated high on psychometric properties or exploring family issues. CONCLUSIONS:
      The process successfully reviewed and provided a framework for assessing
      communication skills instruments. There is a need to expand the study, including
      use of a larger cohort of reviewers to provide more validity to the results and
      minimize potential biases.

PMID- 15739135
TI  - Validation of the HITS domestic violence screening tool with males.
AB  - BACKGROUND AND OBJECTIVES: To date, screening tools for domestic violence have
      been validated only for use with female patients. A four-item HITS (Hurt-Insult
      Threaten-Scream) screening tool is one of those instruments. The purpose of the
      current research was to validate the HITS screening tool in a population of male
      patients. METHODS: In Phase I of the study, 78 non-victim male subjects from an
      ambulatory clinic, a Human Immunodeficiency Virus (HIV) clinic, or emergency room
      completed the HITS and the Conflict Tactics Scale to establish the concurrent
      validity of the HITS. In Phase II, Optimal Data Analysis (ODA) was used to
      establish the construct validity of the HITS by identifying the score that
      reliably differentiated Phase I non-victims from 17 self-identified male victims
      of domestic violence. RESULTS: Concurrent validity of the HITS was good. ODA
      found that the score of 11 on the HITS differentiated between non-victims and
      victims. Sensitivity and specificity were 88% and 97%, respectively. Predictive
      values were 97% for non-victims and 88% for victims. The positive and negative
      likelihood ratios were 34.41 and 0.12, respectively. CONCLUSIONS: HITS
      differentiated between male victimized respondents from non-victims in clinical
      settings.

PMID- 15739136
TI  - Listening to patients: cultural and linguistic barriers to health care access.
AB  - BACKGROUND AND OBJECTIVES: Full access to medical care includes cultural and
      linguistic access as well as financial access. We sought to identify cultural and
      linguistic characteristics of low-income, ethnic minority patients' recent
      encounters with health care organizations that impede, and those that increase,
      health care access. METHODS: We conducted four focus groups with ethnically
      homogeneous African American, Latino, Native American, and Pacific Islander
      patients. Study participants were "walked" through the stages of a medical
      encounter and asked to identify physician and staff behaviors that made the
      patient feel more comfortable (a surrogate for increasing access) and behaviors
      that made the patient feel less comfortable (a surrogate for decreasing access).
      RESULTS: African American and Native American patients in particular expressed
      overall satisfaction with their physicians' services. Patients from all groups
      saw nonphysician staff as frequently impeding access. Based on perceptions of
      negative stereotypes, Native American and Pacific Islander patients reported
      hostility toward physicians' efforts at prevention and patient education.
      CONCLUSIONS: For the ethnic minority patients in our study, most perceived that
      cultural impediments to access involved nonphysician staff. Closer collaborations
      between health care organizations and ethnic minority communities in the
      recruitment and training of staff may be needed to improve cultural and
      linguistic access to care.

PMID- 15739137
TI  - Active precepting in the residency clinic: a pilot study of a new model.
AB  - OBJECTIVE: This study's objective was to develop and implement a model of "active
      precepting" as a teaching and patient care quality improvement project at a
      community-based family medicine residency program. METHODS: The Prepare,
      Orchestrate, Educate, Review (POwER) model was developed with input from faculty,
      students, residents, and staff. Five measures of conformance to the model were
      monitored with daily feedback cards from November 2001 to February 2002. Faculty,
      residents, and clinic staff were surveyed and interviewed after the intervention
      for perceptions about active precepting. Two follow-up patient flow studies were
      completed for concomitant quality improvement efforts, and those findings were
      reviewed along with intervention findings. RESULTS: Preceptors reported reviewing
      resident schedules prior to clinic sessions more often after the model was put in
      place, and clinic staff reported that residents and faculty were more willing to
      help solve problems. Concurrent flow studies showed that patient time in clinic
      decreased from 110 minutes before the intervention to < 70 minutes after, while
      resident time with patients, including precepting time, decreased from 44 minutes
      to < 30 minutes. CONCLUSIONS: Our results point to the potential of the POwER
      model of active precepting to contribute to improved patient care, teaching,
      stakeholder satisfaction, and better flow in the family medicine teaching clinic.

PMID- 15739138
TI  - Primary care renewal: regional faculty development and organizational change.
AB  - BACKGROUND: Many reports, including the Future of Family Medicine, have called
      for change in primary care, but few have defined, implemented, and evaluated
      mechanisms to address such change. The regional, interdisciplinary Primary Care
      Renewal Project was designed to address problems in primary care practice and
      teaching related to practice management, compensation, increasing responsibility
      for teaching, and faculty development. METHODS: Twelve northeastern US medical
      schools assembled a conference attended by teams of key stakeholders representing
      both clinical and educational missions. Teams developed and implemented an
      institutional plan to address identified needs. Outcome data was collected
      during, and for 1 year after, the conference. RESULTS: Findings demonstrate novel
      ways of improving learning experiences, coordinating and centralizing planning
      efforts, and addressing faculty needs. The magnitude of organizational change
      ranged from establishing new administrative units with significant institutional
      authority (eg, restructuring dean's office) to enhancing the strategic planning
      process and refining mission statements to reflect emphasis on primary care.
      CONCLUSIONS: A well-planned, regional interdisciplinary effort that fosters the
      development of concrete plans can be associated with significant change in
      medical education. A central theme emerged--that primary care medicine will
      survive only if institutions align their educational and clinical missions and
      foster system-wide change.

PMID- 15739139
TI  - Journal Policy Statement--IRB approval for educational research.

PMID- 15739140
TI  - End-of-life decisions by GPs.

PMID- 15739142
TI  - Free vascularized fibula grafts in limb-salvage surgery.
AB  - The authors review the outcome of a consecutive series of 24 free vascularized
      fibular grafts performed as part of a limb-salvage procedure following tumor
      excision. There were 15 women and nine men with a mean age of 26 years (range: 6
      to 52 years). The minimum follow-up was 12 months. The mean length of the graft
      was 13.1 cm. (range: 4.5 to 25 cm). Fifteen grafts were used in the upper limb,
      eight in the lower limb, and one in the pelvis. Bony union was achieved in 21/24
      patients at a mean of 9.3 months. Complications occurred in 13/24 patients of
      whom 11 required a second operation. Four patients died of metastatic disease.
      The mean Musculoskeletal Tumor Society (MSTS) functional score in the remaining
      20 was 84.5 percent, with 16 patients having a good or excellent outcome. Free
      vascularized fibula grafts offer a reliable method of reconstruction after
      excision of bone tumors. Although the incidence of complications appears high,
      they are relatively easy to correct, bony union is achieved in the majority, and
      functional outcome is good.

PMID- 15739143
TI  - Arterialized venous flow-through flap for simultaneous reconstruction of a radial
      artery defect and palmar forearm soft-tissue loss from sarcoma resection.
AB  - A 50-year-old right-handed male presented with a previously incompletely excised
      low-grade fibrous histiocytoma on his distal radial palmar forearm. Reoperative
      wide resection resulted in a segmental defect of the radial artery and a large
      soft-tissue defect with exposed tendons denuded of paratenon. An arterialized
      venous fasciocutaneous flow-through flap, measuring 8 x 3 cm, was harvested from
      the dorsal ipsilateral hand and used to reconstruct both the soft-tissue and the
      segmental radial-artery defects. A full-thickness skin graft was harvested from
      the ipsilateral groin to cover the dorsal hand wound. Moderate venous congestion
      was noted in the flap on postoperative day 1 and treated with four days of
      leeches. Approximately 10 percent of the flap was lost due to the venous
      congestion. The flap healed well without further complications. At 33 months the
      flap remained well-perfused, with excellent flow through the reconstructed radial
      artery evidenced by both clinical examination and by color vascular Doppler exam.
      The patient had full range of motion in his right hand despite initial
      postoperative stiffness and reported no cold intolerance in the right hand. There
      has been no local recurrence of the sarcoma. The authors believe that this is the
      largest arterialized venous flow-through flap currently reported to have
      survived, as well as the first reported case of its use for the simultaneous
      reconstruction of a radial artery defect and an associated soft-tissue loss.

PMID- 15739144
TI  - Free muscle flap transfer as a lymphatic bridge for upper extremity lymphedema.
AB  - There are limited reports in the literature describing the use of muscle or skin
      pedicle flaps as a lymphatic bridge to treat obstructive lymphedema. This report
      demonstrates the successful use of a free muscle flap for a circumferential scar
      of a forearm as treatment for obstructive lymphedema. Lymphatic drainage is
      demonstrated across the free flap by lymphoscintigraphy postoperatively. This is
      the first case report using a free muscle flap to reestablish lymphatic flow
      across an area of obstructive limb lymphedema.

PMID- 15739145
TI  - Combined rotational osteotomy and vascularized iliac bone graft for advanced
      osteonecrosis of the femoral head.
AB  - This paper describes the rationale and technique for a combined procedure of
      transtrochanteric rotational osteotomy and vascularized iliac bone grafting in
      cases of osteonecrosis of the femoral head with an extensive and widely collapsed
      necrotic lesion in young patients. The authors performed this combined operation
      for 12 joints in 12 patients over 14 years from 1984 until 1997. At a mean of 81
      months after the operation, in eight patients who had no pain, the average Harris
      hip score was 90.0 points. Postoperative radiographic evaluation revealed that
      collapse (more than 2 mm) of the femoral head was prevented in ten patients.
      Conversion to an endoprosthesis was avoided in all patients except one in this
      series. The authors recommend this procedure for advanced and extensive
      osteonecrosis of the femoral head, especially in young patients, to preserve the
      joint, even though it is a relatively complex procedure.

PMID- 15739146
TI  - Versatility of the lateral arm free flap in various anatomic defect
      reconstructions.
AB  - The free lateral arm flap may be harvested as a fascial, fasciocutaneous, or
      osteofasciocutaneous flap. Simultaneous flap elevation with preparation of the
      recipient site, easy dissection, minimal donor-site morbidity, and a constant
      vascular anatomy with long pedicle are advantages of the flap. In this study, the
      authors present 18 patients operated on between January, 2002 and August, 2003 in
      whom 18 free lateral arm flaps were utilized. There were four women and 14 men,
      and the mean patient age was 40 years. Thirteen fasciocutaneous, three fascial,
      and two osteofasciocutaneous flaps were used. Flaps were employed for the
      reconstruction of the lower extremity in five patients, upper extremity in nine
      patients, and head and neck in four patients. Thirteen flaps were elevated under
      axillary block and five flaps under general anesthesia. Aspirin, dipirydamol,
      dextran, and chlorpromazine were administered postoperatively. Venous
      insufficiency developed in two lower-extremity reconstructions on postoperative
      day 1. Venous thromboses were detected, anastomoses were re-done, and flaps
      healed uneventfully. No other postoperative complication was observed in the
      other patients. The free lateral arm flap may be used in various anatomic defects
      with various indications. It may be elevated under axillary block for extremity
      reconstructions.

PMID- 15739147
TI  - Evaluation of the donor site in patients who underwent reconstruction with a free
      radial forearm flap.
AB  - A major disadvantage of free radial forearm flaps is the conspicuous donor site.
      However, there have been few studies on donor scars. The authors evaluated the
      donor site in patients who underwent oral-floor reconstruction with a free radial
      forearm flap. The subjects were 23 patients (19 males and four females) who
      underwent reconstruction with a free radial forearm flap following resection of a
      malignant oral tumor, and were followed for 1 year or longer. The fasciocutaneous
      flap collection site was closed by full-thickness skin graft (FTSG) from the
      groin with tie-over dressing. All grafts took perfectly. At the scar at the donor
      site, five items (pigmentation, scar width, depression, wrist mobility, and
      sensory abnormalities) were evaluated. Depression and pigmentation were often
      observed, but patient dissatisfaction was slight. While their main postoperative
      concern was the oral reconstruction site, after about 1 year, the donor site
      became more important to patients. However, the results were good. A 100 percent
      take of the FTSG at the donor site should produce good results. Surgeons should
      pay adequate attention not only to the outcome at the reconstruction site, but
      also to the closure of the donor site.

PMID- 15739148
TI  - Fibula osteoseptocutaneous flap with a variant perforator and peroneal artery
      arising from the anterior tibial artery.
AB  - Since the report of the first cases of vascularized free fibula graft for
      treatment of open fracture of the tibia and fibula in 1975, there have been many
      other reports of the use of vascularized free osteocutaneous fibula flaps for
      reconstruction of the mandible or lower leg. Usually, these flaps have a single
      pedicle composed of the peroneal artery, to supply the fibula with septocutaneous
      or musculocutaneous branches arising from the peroneal artery to supply the
      lateral skin of the leg. Although some authors have reported variant perforators,
      there have been no reports of the peroneal artery arising from the anterior
      tibial artery and perforator arising from the posterior tibial artery. This is
      the first report of a variant of the peroneal artery and perforator using a
      vascularized free osteocutaneous fibula flap.

PMID- 15739149
TI  - Interrupted micro-mattress sutures solve vessel-size discrepancy.
AB  - Although technical refinements have improved microvascular techniques, the
      problem of vessel-size discrepancy between donor and recipient vessels is still
      unsolved and can decrease the success rate of free tissue transfer. In fact, if
      vessels with incongruent diameters are not adequately anastomosed, the risk of
      free flap failure is increased. In this paper, the authors present a new type of
      microvascular anastomosis to overcome the problem of vessel-size discrepancy.
      Interrupted mattress sutures are placed in end-to-end anastomosis narrowing the
      wider diameter and compensating for the diameter incongruency. The surgical
      technique and main clinical applications of the interrupted micro-mattress
      sutures are described in detail. Indications and advantages are discussed.

PMID- 15739150
TI  - Invited discussion: "Shape-modified method using the radial forearm perforator
      flap for reconstruction of soft-tissue defects of the scalp" (J Reconstr
      Microsurg 2005;21:21-24).

PMID- 15739151
TI  - Sural nerve harvest: anatomy and technique.
AB  - A minimally-invasive technique of sural nerve harvesting using an initial blunt
      tip harvesting device, combined with a recessed sharp cutting mechanism for final
      severance of the nerve, has been developed. Important surgical landmarks have
      been established, based on a review of the anatomy of the sural nerve. Harvesting
      is begun through a small incision at the level of the lateral malleolus, thereby
      identifying the nerve and inserting the nerve-harvesting device. An additional
      small incision, if needed, is placed at the junction of the middle and distal
      thirds of the lower leg, a landmark at which an anastomosis between the medial
      and lateral sural cutaneous nerves is seen in at least 74 percent of patients.
      When this anastomosis is palpated, the lateral sural cutaneous nerve is
      visualized and divided, and the dissection of the medial sural cutaneous nerve
      proceeds in a proximal direction. At the distal end below the popliteal fossa,
      the cutting mechanism is safely deployed, transecting the nerve. This combination
      of a limited incision approach with the blunt harvester and sharp, protected
      division provides 30 to 35 cm of sural nerve graft in the great majority of
      patients, while reducing the complications often associated with open techniques
      and minimally-invasive techniques that rely on sharp or blunt instrumentation.

PMID- 15739152
TI  - Comparison of bacterial inoculation and transcutaneous oxygen tension in the
      rabbit S1 perforator and latissimus dorsi musculocutaneous flaps.
AB  - Muscle and musculocutaneous flaps have been used reliably in reconstruction of
      soft-tissue defects for many years. Previous experimental studies have shown
      musculocutaneous flaps to be superior to the random pattern and fasciocutaneous
      flaps in the management of infected wounds. Over the past decade, perforator
      flaps have gained acceptance as alternative methods of reconstruction in the
      clinical setting that can decrease donor-site morbidity and hospital stay, and
      increase patient satisfaction. The authors theorized that perforator flaps may be
      able to handle infected wounds better than random pattern and fasciocutaneous
      flaps because their blood supply is essentially the same as many of their
      musculocutaneous counterparts. The goal of this study was to compare the S1
      perforator-based skin flap and latissimus dorsi musculocutaneous flap in the
      dorsal flank of the rabbit with the introduction of bacteria to simulate both
      superficial and deep wound infection. Measurements of oxygen tension and regional
      perfusion index were performed on both types of flaps to ascertain their
      viability and capacity to heal. The authors found no statistical significance
      between latissimus dorsi musculocutaneous and S1 perforator flaps in the rabbit
      with respect to superficial and deep wound infections. The regional perfusion
      index was calculated for postoperative days 1, 2, and 4. No statistically
      significant difference between the two flaps using the regional perfusion index
      could be identified. Additionally, regional perfusion for both types of flaps was
      greater than 0.6, indicating that their capacity to heal wounds is similar.

PMID- 15739153
TI  - Effects of time lapse on results of partial nerve injury repair.
AB  - Partial nerve severance is a problem in peripheral-nerve surgery. It should be
      repaired without tension for a good functional result. There is usually no
      trouble in repairing acute injuries. But, as time passes, it may be difficult to
      establish a proper end-to-end repair, and this cause more tension at the repair
      sites. In this study, the critical time lapse for a deleterious effect was
      evaluated. Thirty rats were used, with partial nerve severance repaired
      immediately or at 10 or 20 days later. At 2, 4, 8, 12, 20, and 28 weeks,
      functional assessment of nerve regeneration was performed using walking-track
      analysis. Functionally, the sciatic index values were very close to each other in
      the immediate and 10-day-delay group, but the difference between these groups and
      the 20-day-delay group was statistically significant. The study suggests a
      critical period of about 2 weeks after partial nerve section before irreversible
      changes occur. Although this is not applicable to human models, it implies
      further work on a primate model for determining a reliable time-lapse period.

PMID- 15739155
TI  - A new approach for sequencing human IRS1 phosphotyrosine-containing peptides
      using CapLC-Q-TOF(micro).
AB  - Reversible phosphorylation of proteins functions as a biological switching
      network for activation and inhibition of downstream biological processes. Since
      phosphorylations of these sites are often transient processes, and hence sub
      stoichiometric, systematic characterization of phosphorylation sites is a
      formidable challenge. In this work, a new approach was developed to pinpoint
      phosphotyrosine sites on tyrosine-containing peptides. This required (1) the
      development of a new and highly sensitive nano-electrospray assembly and (2)
      validation of the concept that the specificity and detection limit for trace
      levels of phosphotyrosine immonium ion in peptide mixtures from protein digests
      can be increased by varying the collision energy. With our method, an automatic
      tandem mass spectrometric analysis of peptides eluted from a C(18) capillary
      liquid chromatographic column is triggered by a positive confirmation of
      phosphotyrosine immonium ion in a time-of-flight mass spectrometric survey. The
      approach was tested by analyzing the phosphorylation of human IRS-1 peptides that
      interact with the Src-homology 2 domain and mixtures of these peptides with
      tryptic digests of bovine serum albumin and horse heart myoglobin.

PMID- 15739156
TI  - Electrospray ionization tandem mass spectrometric characteristics of hairpin
      artificial minic polypeptide.

PMID- 15739157
TI  - Characterization of some synthetic Ru and Ir complexes by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS) was applied to the analysis of Ru(OCOCF(3))(2)(CO)(PPh(3))(2),
      Ru(OCOC(3)F(7))(2)(CO)(PPh(3))(2), Ir(tBuppy)(3) and Ir(ppy)(2)(acac) complexes.
      A troublesome problem in the MALDI-TOFMS characterization of these metal
      complexes is the possible replacement of complex ligands by matrix. In this
      contribution, 10 matrices, ranging from acidic to basic, were investigated: alpha
      cyano-4-hydroxycinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (DHB), sinapinic
      acid (SA), dithranol, 2,4,6-trihydroxyactophenone (THAP), 6-azo-2-thiothymine
      (ATT), norharman, 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2
      enylidene]malononitrile (DCTB), 4-nitroaniline (NA) and 2-amino-5-nitrophyridine
      (ANP). With most of the matrices, including the neutral and basic ones, matrix
      substitution of ligand could clearly be detected. Based on the experimental
      results, possible mechanisms of matrix substitution were discussed. It was
      demonstrated that the ligand exchange process might also occur through the gas
      phase reactions initiated by laser shots. Among the matrices tested, DCTB was
      found to be the best one for the complexes that are prone to ligand exchange by
      matrix.

PMID- 15739154
TI  - Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall
      syndromes: robust phenotype prediction from the type and position of GLI3
      mutations.
AB  - Mutations in the GLI3 zinc-finger transcription factor gene cause Greig
      cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which
      are variable but distinct clinical entities. We hypothesized that GLI3 mutations
      that predict a truncated functional repressor protein cause PHS and that
      functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we
      screened patients with PHS and GCPS for GLI3 mutations. The patient group
      consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We
      detected 47 pathological mutations (among 60 probands); when these were combined
      with previously published mutations, two genotype-phenotype correlations were
      evident. First, GCPS was caused by many types of alterations, including
      translocations, large deletions, exonic deletions and duplications, small in
      frame deletions, and missense, frameshift/nonsense, and splicing mutations. In
      contrast, PHS was caused only by frameshift/nonsense and splicing mutations.
      Second, among the frameshift/nonsense mutations, there was a clear genotype
      phenotype correlation. Mutations in the first third of the gene (from open
      reading frame [ORF] nucleotides [nt] 1-1997) caused GCPS, and mutations in the
      second third of the gene (from ORF nt 1998-3481) caused primarily PHS.
      Surprisingly, there were 12 mutations in patients with GCPS in the 3' third of
      the gene (after ORF nt 3481), and no patients with PHS had mutations in this
      region. These results demonstrate a robust correlation of genotype and phenotype
      for GLI3 mutations and strongly support the hypothesis that these two allelic
      disorders have distinct modes of pathogenesis.

PMID- 15739158
TI  - A new high-performance liquid chromatographic/electrospray ionization tandem mass
      spectrometric method for the simultaneous determination of cyclophosphamide,
      methotrexate and 5-fluorouracil as markers of surface contamination for
      occupational exposure monitoring.
AB  - A new high-performance liquid chromatographic/electrospray ionization tandem mass
      spectrometric (HPLC/ESI-MS/MS) method was developed for the simultaneous
      quantification of 5-fluorouracil (5FU), methotrexate (MTX) and cyclophosphamide
      (CP) in environmental samples. These compounds, commonly used in the treatment of
      cancer, are recognized as genotoxic. In order to estimate the occupational
      exposure of hospital personnel handling these drugs, wipe samples were taken from
      the working surfaces and directly analyzed (with trophosphamide as internal
      standard) using a reversed-phase capillary column and MS/MS detection. This is
      the first HPLC/MS/MS method for the simultaneous determination of 5FU, MTX and
      CP. The present method offers high sensitivity, with detection limits of 1.1
      microg l(-1) for MTX and CP and 33.3 microg l(-1) for 5FU, avoiding any sample
      preconcentration procedure. Rapidity, specificity, high accuracy (mean values
      between 92.4 and 99.9%) and precision (mean RSD values between 3.4 and 12.1%)
      make the method suitable for the routine determination of these three
      antineoplastic drugs.

PMID- 15739159
TI  - Direct exposure electron ionization mass spectrometry and gas chromatography/mass
      spectrometry techniques to study organic coatings on archaeological amphorae.
AB  - Two different analytical approaches, direct exposure electron ionization mass
      spectrometry (DE-MS) and gas chromatography/mass spectrometry (GC/MS), were
      compared in a study of archaeological resinous materials. DE-MS was found to be
      an efficient fingerprinting tool for the fast screening of organic archaeological
      samples and for providing information on the major components. GC/MS appeared to
      be more efficient in unravelling the sample composition at a molecular level,
      despite the long analysis time and the need for a wet chemical pretreatment. Both
      procedures were applied to characterize the organic material present as coatings
      in Roman and Egyptian amphorae. DE-MS successfully identified abietanic
      compounds, hence a diterpenic resinous material could be identified and its
      degree of oxidation assessed. GC/MS enabled us to identify dehydroabietic acid, 7
      oxodehydroabietic acid, 15-hydroxy-7-oxodehydroabietic acid, 15
      hydroxydehydroabietic acid, retene, tetrahydroretene, norabietatriene,
      norabietatetraene and methyl dehydroabietate. These oxidized and aromatized
      abietanes provided evidence that the amphorae examined were waterproofed with a
      pitch produced from resinous wood of plants from the Pinaceae family. The
      chemometric evaluation of the GC/MS data highlighted significant chemical
      differences between the pitches found in the two archaeological sites, basically
      related to differences in the production techniques of the materials and in their
      degradation pathways.

PMID- 15739160
TI  - The granzyme B inhibitor proteinase inhibitor 9 (PI9) is expressed by human mast
      cells.
AB  - The activity of granzyme B, a main effector molecule of cytotoxic T lymphocytes
      (CTL) and natural killer cells, is regulated by the human intracellular serpin
      proteinase inhibitor 9 (PI9). This inhibitor is particularly expressed by CTL and
      dendritic cells, in which it serves to protect these cells against endogenous and
      locally released granzyme B. Moreover, PI9 expression by neoplastic cells may
      constitute one of the mechanisms for tumors to escape immune surveillance. Here
      we show that PI9 is also expressed by human mast cells. In immunohistochemical
      studies using a PI9-specific monoclonal antibody, strong cytoplasmic staining for
      PI9 was found in normal mast cells in various tissues throughout the body. In
      addition, in 80% of all cases of cutaneous and systemic mastocytosis tested the
      majority of the mast cells expressed PI9. As an in vitro model for PI9 expression
      by mast cells, we studied expression by the human mast cell line HMC-1.
      Stimulation of HMC-1 with PMA and the calcium ionophore A23187 resulted in a
      marked increase of PI9 expression. Thus, PI9 is expressed by activated mast
      cells. We suggest that this expression serves to protect these cells against
      apoptosis induced by granzyme B released during initiation of the local
      inflammatory response.

PMID- 15739161
TI  - Analysis of FeII-mediated decomposition of a linoleic acid-derived lipid
      hydroperoxide by liquid chromatography/mass spectrometry.
AB  - Intracellular Fe(II), which is up-regulated during oxidative stress and during
      iron overload, induces the formation of a hydroxyl radical by Fenton chemistry.
      The hydroxyl radical can convert the prototypic omega-6 polyunsaturated fatty
      acid, linoleic acid, to 13-hydroperoxy-9,11-(Z,E)-octadecadienoic acid (13
      HPODE). Cyclooxygenases can also convert linoleic acid to 13(S)-HPODE during
      oxidative stress. Subsequent Fe(II)-mediated decomposition to protein- and DNA
      reactive bifunctional electrophiles was examined by normal-phase liquid
      chromatography (LC)/atmospheric pressure chemical ionization (APCI)/mass
      spectrometry. The potential individual bifunctional electrophiles trans-4,5-epoxy
      2(E)-decenal (EDE), cis-EDE, 4-oxo-2(E)-nonenal (ONE) and 4-hydroxy-2(E)-nonenal
      (HNE) exhibited protonated molecular ions at m/z 169, 169, 155 and 157,
      respectively. The MH(+) ion at m/z 173 for 4-hydroperoxy-2(E)-nonenal (HPNE) was
      very weak with an ion corresponding to the loss of OH at m/z 156 as the major ion
      in the APCI mass spectrum. The bifunctional electrophiles were all separated
      under normal-phase LC conditions. Interestingly, ions corresponding to ONE and
      HNE were detected at the same retention time as HPNE, suggesting that it
      decomposed in the source of the mass spectrometer to ONE and HNE. All five
      bifunctional electrophiles were formed when 13-HPODE was treated with 50 microM
      Fe(II). At this concentration of Fe(II), the addition of vitamin C resulted in
      increased bifunctional electrophile formation. At higher concentrations of Fe(II)
      (500 microM to 2 mM), no HPNE was detected and there was no additive effect of
      vitamin C. Additional experiments with synthetic HPNE revealed that it was
      quantitatively converted to a mixture of ONE and HNE by Fe(II). The HNE is
      thought to arise from a one-electron reduction of an alkoxy radical derived from
      HPNE. In contrast, ONE can arise through an alpha-cleavage of the HPNE-derived
      alkoxy radical or by direct dehydration of HPNE.

PMID- 15739162
TI  - Dendritic cells govern induction and reprogramming of polarized tissue-selective
      homing receptor patterns of T cells: important roles for soluble factors and
      tissue microenvironments.
AB  - Tissue-selective homing is established during naive T cell activation by the
      tissue microenvironment and tissue-specific dendritic cells (DC). The factors
      driving induction and maintenance of T cell homing patterns are still largely
      unknown. Here we show that soluble factors produced during the interaction of T
      cells with CD11c(+) DC isolated from skin- or small intestine-associated tissues
      differentially modulate expression of the corresponding tissue-selective homing
      receptors (E-selectin ligands and alpha4beta7 integrin/CCR9, respectively) on
      murine CD8(+) T cells. Injection of tissue-specific DC via different routes
      induces T cells with homing receptors characteristic of the corresponding local
      tissue microenvironment, independent of the origin of the DC. These data indicate
      an important role for signals delivered in trans. Moreover, DC can reprogram the
      homing receptor expression on T cells previously polarized in vitro for homing to
      skin or small intestine. Importantly, skin-homing memory T cells stimulated
      directly ex vivo can also be reprogrammed by intestinal DC to a gut-homing
      phenotype. Our results show that tissue-selective homing receptor expression on
      effector and memory T cells is governed by inductive as well as suppressive
      signals from both DC and tissue microenvironments.

PMID- 15739163
TI  - Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll
      like receptor 2, and phosphatidylinositol-3-kinase.
AB  - CD11b-CD18 and other integrins play important roles in immunity and inflammation
      and require prior activation through inside-out signaling to efficiently bind
      their ligands. We present evidence for a novel TLR2-dependent signaling pathway
      that leads to CD11b-CD18 activation in human monocytes or neutrophils upon
      recognition of Porphyromonas gingivalis fimbriae through CD14. The activated
      binding-state of CD11b-CD18, which involves induction of conformational changes,
      was monitored through detection of an activation-specific epitope of CD11b. The
      ability of fimbriae to induce this activation epitope was significantly inhibited
      by a mAb to TLR2, but not to TLR4 or unrelated surface molecules. Moreover, the
      ability of fimbriae to activate CD11b-CD18 was significantly inhibited by
      pharmacological inhibitors of phosphatidylinositol-3-kinase but not of PKC or of
      p38 mitogen-activated protein kinase. The signaling pathway activated by fimbriae
      is distinct from that which is activated by N-formyl-Met-Leu-Phe, a prototypical
      integrin activator, since the former was insensitive to pertussis toxin. This
      novel function of TLR2 as a signaling receptor for pathogen-induced activation of
      CD11b-CD18 may play a significant role in infection-driven chronic inflammatory
      conditions, such as periodontal disease or atherosclerosis, where P. gingivalis
      has been implicated.

PMID- 15739164
TI  - An intron GATA-binding site regulates chromatin accessibility and is essential
      for IL-4 gene expression in mast cells.
AB  - Several GATA-binding sites have been identified in regions both distal to and
      within the murine IL-4 gene locus, yet their relative role in IL-4 expression is
      unknown. Chromatin immunoprecipitation assays were used to demonstrate that GATA
      1 and GATA-2 are associated with a regulatory element within the second intron of
      the IL-4 gene in murine mast cells in vivo. Furthermore, although expression from
      a stably integrated wild-type IL-4 minigene parallels endogenous IL-4 gene
      expression, mutation of the GATA-binding element, but not an SP-1-binding site,
      virtually abolishes transcription in mast cells, an observation that correlates
      with the local loss of H3 and H4 histone acetylation in the intron. Treatment
      with the chromatin remodeling agents 5 azacytidine and trichostatin A can restore
      this defect in transcription. These results define an essential site of GATA
      influence on IL-4 expression in mast cells and directly support the idea that
      GATA factors have a profound impact on locus accessibility.

PMID- 15739165
TI  - Airway inflammation: chemokine-induced neutrophilia and the class I
      phosphoinositide 3-kinases.
AB  - Class I phosphoinositide 3-kinases (PI3K) are known to play a significant role in
      neutrophil chemotaxis. However, the relative contributions of different PI3K
      isoforms, and how these impact on lung inflammation, have not been addressed. In
      vitro studies using wild-type and PI3Kgamma knockout neutrophils demonstrated the
      major role of the gamma isoform in chemotactic but not chemokinetic events. This
      was confirmed by a model of direct chemokine instillation into the airways in
      vivo. Within all studies, a low yet significant degree of neutrophil movement in
      the absence of PI3Kgamma could be observed. No role for the delta isoform was
      demonstrated both in vitro and in vivo using PI3Kdelta kinase-dead knock-in mice.
      Moreover, further studies using the broad-spectrum PI3K inhibitors wortmannin or
      LY294002 showed no other class I PI3K isoforms to be involved in these
      chemotactic processes. Here, we identify a contributory PI3K-independent
      mechanism of neutrophil movement, yet demonstrate PI3Kgamma as the pivotal
      mediator through which the majority of neutrophils migrate into the lung in
      response to chemokines. These data resolve the complexities of chemokine-induced
      neutrophilia and PI3K signaling and define the gamma isoform as a promising
      target for new therapeutics to treat airway inflammatory diseases.

PMID- 15739166
TI  - Protection against tetanus toxin using a plant-based vaccine.
AB  - Plant-expressed vaccines may provide a unique opportunity for generating anti
      pathogen immunity, especially in countries where cold storage is lacking. In the
      following study, we show that soluble protein from tobacco leaves expressing
      fragment C of tetanus toxin protected mice against a lethal tetanus toxin
      challenge. More importantly, we show that a single intranasal (i.n.) vaccination
      was as efficient as oral delivery, inducing high levels of activated CD4(+) T
      cells and anti-toxin antibody. Unlike the oral route, i.n. delivery did not
      require the presence of adjuvant (cholera toxin). Indeed, addition of cholera
      toxin induced bystander immune responses to plant proteins as well. This is the
      first study documenting protective immunity by a single i.n. dose of plant
      vaccine. Plant-based vaccines are promising because they are more heat stable,
      are easy to produce, cheap and do not require needles.

PMID- 15739167
TI  - Scant activation of CD8 T cells by antigen loaded on heat shock protein.
AB  - Heat shock proteins (HSP) not only function as chaperones for denatured proteins
      but also for antigenic peptides, thus inducing protective T cell responses. Here
      we show that vaccination with peptide-loaded HSP70 causes initial interferon
      gamma production by murine CD8 T cells but no T cell expansion. These CD8 T cells
      lacked cytotoxic activity in vitro and in vivo, which was not due to apoptosis.
      Restimulation with peptide-pulsed dendritic cells both bypassed the proliferative
      block and suspended the non-protective state of CD8 T lymphocytes in an infection
      model with the bacterial pathogen, Listeria monocytogenes. Cotransfer of antigen
      specific CD4 T cells circumvented the proliferative arrest of CD8 T cells. Our
      data suggest that HSP vaccines induce CD8 T cell unresponsiveness unless
      proficient help is provided. Assuming that this model reflects the antigenically
      experienced human condition where immunological space is restricted and any T
      cell response possibly leads to suppression of heterologous reactions, our
      findings bear implications for rational vaccination protocols including those for
      immunocompromised patients.

PMID- 15739168
TI  - The carboxyl terminus of the chemokine receptor CCR3 contains distinct domains
      which regulate chemotactic signaling and receptor down-regulation in a ligand
      dependent manner.
AB  - The chemokine receptor CCR3 regulates the chemotaxis of leukocytes implicated in
      allergic disease, such as eosinophils. Incubation of eosinophils with CCL11,
      CCL13 or CCL5 resulted in a rapid decrease of cell-surface CCR3 which was
      replicated using CCR3 transfectants. Progressive truncation of the CCR3 C
      terminus by 15 amino acids produced three constructs, Delta340, Delta325 and
      Delta310. Delta340 and Delta325 were able to bind CCL11 with affinities similar
      to wild-type CCR3. Delta340 transfectants exhibited enhanced migration and
      reduced receptor down-regulation in response to CCL11 and CCL13. Delta325
      transfectants displayed chemotactic responses to CCL11 and CCL13 similar to wild
      type CCR3, and had impaired down-regulation when stimulated with CCL13 but not
      CCL11. In contrast, neither the Delta325 nor Delta340 truncation affected
      chemotaxis or receptor down-regulation induced by CCL5. Delta310 transfectants
      bound CCL11 poorly and were biologically inactive. Inhibitors of p38 mitogen
      activated protein kinase and PI3-kinase antagonized eosinophil shape change
      responses and chemotaxis of transfectants to CCL11 and CCL13. In contrast, shape
      change but not chemotaxis was sensitive to inhibition of the extracellular signal
      regulated kinase kinase pathway suggesting differential regulation of the two
      responses. Thus, the CCR3 C terminus contains distinct domains responsible for
      the regulation of receptor desensitization and for coupling to chemotactic
      responses.

PMID- 15739169
TI  - Large-scale production of pharmaceuticals by marine sponges: sea, cell, or
      synthesis?
AB  - Marine sponges are known to produce an overwhelming array of secondary
      metabolites with pharmaceutical potential. The technical and economical potential
      of using marine sponges for large-scale production of these compounds was
      assessed for two cases: the anticancer molecule halichondrin B from a
      Lissodendoryx sp., and avarol from Dysidea avara for its antipsoriasis activity.
      An economic and technical analysis was done for three potential production
      methods: mariculture, ex situ culture (in tanks), and cell culture. We concluded
      that avarol produced by mariculture or ex situ culture could become a viable
      alternative to currently used pharmaceuticals for the treatment of psoriasis.
      Production of halichondrin B from sponge biomass was found to not be a feasible
      process, mainly due to the extremely low concentration of the compound in the
      sponge. Technical feasibility was also analyzed for five alternatives: chemical
      synthesis, wild harvest, primmorph culture, genetic modification and semi
      synthesis. It was concluded that the latter two approaches could prove to be
      valuable methods for the production of pharmaceuticals, based on chemical
      structures of secondary metabolites present in trace amounts in marine sponges.

PMID- 15739170
TI  - Display of lipase on the cell surface of Escherichia coli using OprF as an anchor
      and its application to enantioselective resolution in organic solvent.
AB  - We have developed a new cell surface display system using a major outer membrane
      protein of Pseudomonas aeruginosa OprF as an anchoring motif. Pseudomonas
      fluorescens SIK W1 lipase gene was fused to the truncated oprF gene by C-terminal
      deletion fusion strategy. The truncated OprF-lipase fusion protein was
      successfully displayed on the surface of Escherichia coli. Localization of the
      truncated OprF-lipase fusion protein was confirmed by western blot analysis,
      immunofluorescence microscopy, and whole-cell lipase activity. To examine the
      enzymatic characteristics of the cell surface displayed lipase, the whole-cell
      enzyme activity and stability were determined under various conditions. Cell
      surface displayed lipase showed the highest activity at 37 degrees C and pH 8.0.
      It retained over 80% of initial activity after incubation for a week in both
      aqueous solution and organic solvent. When the E. coli cells displaying lipases
      were used for enantioselective resolution of racemic 1-phenylethanol in hexane,
      (R)-phenyl ethyl acetate was successfully obtained with the enantiomeric excess
      of greater than 96% in 36 h of reaction. These results suggest that E. coli cells
      displaying lipases using OprF as an anchoring motif can be employed for various
      biotechnological applications both in aqueous and nonaqueous phases.

PMID- 15739171
TI  - Operational and microbiological aspects of a bioaugmented two-stage biotrickling
      filter removing hydrogen sulfide and dimethyl sulfide.
AB  - A two-stage biotrickling filter was developed for removing dimethyl sulfide (DMS)
      and hydrogen sulfide (H2S). The first biotrickling filter (ABF) was inoculated
      with Acidithiobacillus thiooxidans and operated without pH control, while the
      second biotrickling filter (HBF) was inoculated with Hyphomicrobium VS and
      operated at neutral pH. High DMS elimination capacities were observed in the HBF
      (8.2 g DMS m(-3) h(-1) at 90% removal efficiency) after 2 days. Maximal observed
      elimination capacities were 83 g H2S m(-3) h(-1) (100% removal efficiency) and 58
      g DMS m(-3) h(-1) (88% removal efficiency) for the ABF and the HBF, respectively.
      The influence of a decreasing empty bed residence time (120 down to 30 sec) and
      the robustness of the HBF towards changing operational parameters (low pH,
      starvation, and DMS and H2S peak loadings) were investigated. Suboptimal
      operational conditions rapidly resulted in lower DMS removal efficiencies, but
      recovery of the HBF was mostly obtained within a few days. The H2S removal
      efficiency in the ABF, however, was not influenced by varying operational
      conditions. In both reactors, microbial community dynamics of the biofilm and the
      suspended bacteria were investigated, using denaturing gradient gel
      electrophoresis (DGGE). After a period of gradual change, a stable microbial
      community was observed in the HBF after 60 days, although Hyphomicrobium VS was
      not the dominant microorganism. In contrast, the ABF biofilm community was stable
      from the first day and only a limited bacterial diversity was observed. The
      planktonic microbial community in the HBF was very different from that in the
      biofilm.

PMID- 15739172
TI  - Solubility and proteolysis of the Zb-MalE and Zb-MalE31 proteins during
      overproduction in Escherichia coli.
AB  - From the hypothesis that the rate of expression of a nascent polypeptide controls
      the accumulation of soluble full-length protein, accumulation of the model fusion
      proteins Zb-MalE and Zb-MalE31, were studied. MalE and MalE31 are two isoforms of
      the maltose binding protein, differing only in two consecutive amino acids.
      Parameters controlling the expression rate were the transcription rate, which was
      controlled by IPTG induction of the lacUV5 promoter and the substrate addition
      levels during fed-batch cultivation. Results show that the two product proteins
      appear in both soluble and insoluble fractions during cultivation and are both
      subjected to proteolysis. However, the accumulation of the soluble form of Zb
      MalE31 protein is radically lower, at all conditions, due to the small difference
      in primary structure. It was shown that both proteolysis and inclusion body
      formation could be influenced by the selected parameters although a change in
      feed rate had a considerably higher effect. A high concentration of inducer and a
      "high" feed rate result in a low accumulation of soluble product, due to a high
      proteolysis. The concentration of inducer leading to different levels of
      transcription is, however, an efficient tool to influence inclusion body
      formation. At low IPTG concentrations (< or = 5 microM), this formation is almost
      abolished while at a comparatively high concentration (> or = 300 microM) 50% of
      the total product accumulated was in the form of inclusion bodies.

PMID- 15739173
TI  - Bioactivity of diopside ceramic in human parotid saliva.
AB  - Diopside ceramic pellets with a nominal composition of 55.5 wt % SiO(2)-25.9 wt %
      CaO-18.0 wt % MgO were soaked in human parotid saliva (HPS) over different time
      intervals, to investigate the behavior of the material in a natural medium of
      high protein content. The results showed the formation of a hydroxyapatite (HA)
      like layer on the surface of the ceramic, and suggested that the mechanism of HA
      like layer formation in saliva was similar to that showed in vitro test by other
      silica-based materials. The HA-like layer formed at the interface was found to be
      compact, continuous, and composed of many small crystallites with ultrastructure
      similar to that of natural cortical bone and dentine. The study concluded that
      the high pH conditions (9.8) existing right at the ceramic/human parotid saliva
      interface promoted HA-like phase precipitation. At this stage of the study, it is
      possible to suggest that the diopside ceramic could be of interest in specific
      periodontal applications for bone restorative purposes. Morphology, structure,
      and composition of the interfacial reaction product were examined by Scanning and
      Transmission Electron Microscopy techniques (SEM and TEM), combined with Energy
      Dispersive X-say Spectroscopy (EDS). Changes in ionic concentrations were
      measured using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES),
      while the pH right at the interface of diopside/PHS were determined with an Ion
      Sensitive Field Effect Transistor (ISFET-Meter) instruments.

PMID- 15739174
TI  - Cellular effects of low power laser therapy can be mediated by nitric oxide.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to investigate the
      possibility of involvement of nitric oxide (NO) into the irradiation-induced
      increase of cell attachment. These experiments were performed with a view to
      exploring the cellular mechanisms of low-power laser therapy. STUDY
      DESIGN/MATERIALS AND METHODS: A suspension of HeLa cells was irradiated with a
      monochromatic visible-to-near infrared radiation (600-860 nm, 52 J/m2) or with a
      diode laser (820 nm, 8-120 J/m2) and the number of cells attached to a glass
      matrix was counted after 30 minute incubation at 37 degrees C. The NO donors
      sodium nitroprusside (SNP), glyceryl trinitrate (GTN), or sodium nitrite (NaNO2)
      in the concentration range 5 x 10(-9)-5 x 10(-4)M were added to the cellular
      suspension before or after irradiation. The action spectra and the concentration
      and fluence dependencies obtained were compared and analyzed. RESULTS: The well
      structured action spectrum for the increase of the adhesion of the cells, with
      maxima at 619, 657, 675, 740, 760, and 820 nm, points to the existence of a
      photoacceptor responsible for the enhancement of this property (supposedly
      cytochrome c oxidase, the terminal respiratory chain enzyme), as well as
      signaling pathways between the cell mitochondria, plasma membrane, and nucleus.
      Treating the cellular suspension with SNP (5 x 10(-5)M) before irradiation
      significantly modifies the action spectrum for the enhancement of the cell
      attachment property (band maxima at 642, 685, 700, 742, 842, and 856 nm). The
      action of SNP, GTN, and NaNO2 added before or after irradiation depends on their
      concentration and radiation fluence. CONCLUSIONS: The NO donors added to the
      cellular suspension before irradiation eliminate the radiation-induced increase
      in the number of cells attached to the glass matrix, supposedly by way of binding
      NO to cytochrome c oxidase. NO added to the suspension after irradiation can also
      inhibit the light-induced signal downstream. Both effects of NO depend on the
      concentration of the NO donors added. These results indicate that NO can control
      the irradiation-activated reactions that increase the attachment of cells.

PMID- 15739175
TI  - Insights from ab initio quantum chemical calculations into the preferred
      tautomeric forms and binding affinities to CDK2 of substituted pyrazolopyridines.
AB  - Ab initio calculations were employed to compute pKa values and tautomer
      properties of a series of substituted pyrazolopyridines. The results show that
      the neutral 1H tautomer predominates, but upon protonation this proton migrates
      to give the preferred charged [2H,7H] tautomer. The basicity of the
      pyrazolopyridines is correlated with the electron donating capability of the 4
      substituent. Ab initio free energy calculations were also used to identify
      determinants of binding affinity for some recently published pyrazolopyridine
      inhibitors of CDK2. Hydrogen-bonding affinity may be one important component of
      binding strength.

PMID- 15739176
TI  - Generation of peptides by human erythrocytes: facts and artifacts.
AB  - Previously reported data on peptide composition of human erythrocyte lysate were
      obtained under conditions that did not exclude proteolytic degradation of
      hemoglobin in the process of peptide isolation. Comparative chromatographic
      analysis of the diluted erythrocyte lysate incubated in acidic conditions with or
      without proteolytic enzyme inhibitors showed that several peptides earlier
      identified as intraerythrocyte ones in fact result from hemoglobin degradation by
      erythrocyte acidic protease(s) during incubation of the lysate. A rational scheme
      excluding postlysis proteolysis was developed for isolation of peptide fraction.
      Further analysis resulted in determination of structure and content of about 50
      endogenous intraerythrocyte hemoglobin fragments. A primary endopeptidase
      splitting of alpha- and beta-globin chains followed by consecutive exopeptidase
      trimming of primary fragments is suggested as a degradation mechanism. The
      intraerythrocyte peptides were shown to differ from peptides excreted by the
      erythrocytes to the extracellular medium in the primary culture. It was also
      found that intraerythrocyte peptides cannot play the role of precursors of
      hemoglobin fragments present in tissue extracts.

PMID- 15739177
TI  - The effect of higher order RNA processes on changing patterns of protein domain
      selection: a developmentally regulated transcriptome of type 1 inositol 1,4,5
      trisphosphate receptors.
AB  - The domain structure of proteins synthesized from a single gene can be remodeled
      during tissue development by activities at the RNA level of gene expression. The
      impact of higher order RNA processing on changing patterns of protein domain
      selection may be explored by systematically profiling single-gene transcriptomes.
      itpr1 is one of three mammalian genes encoding receptors for the second messenger
      inositol 1,4,5-trisphosphate (InsP3). Some phenotypic variations of InsP3
      receptors have been attributed to hetero-oligomers of subunit isoforms from
      itpr1, itpr2, and itpr3. However, itpr1 itself is subject to alternative RNA
      splicing, with 7 sites of transcript variation, 6 within the ORF. We have
      identified 17 itpr1 subunit species expressed in mammalian brain in ensembles
      that change with tissue differentiation. Statistical analyses of populations
      comprising >1,300 full-length clones suggest that subunit variation arises from a
      variably biased stochastic splicing mechanism. Surprisingly, the protein domains
      of this highly allosteric receptor appear to be assembled in a partially
      randomized way, yielding stochastic arrays of subunit species that form
      tetrameric complexes in single cells. Nevertheless, functional expression studies
      of selected subunits confirm that splicing regulation is connected to phenotypic
      variation. The potential for itpr1 subunits to form hetero-tetramers in single
      cells suggests the expression of a developmentally regulated continuum of
      molecular forms that could display diverse properties, including incremental
      sensitivities to agonist activation and varying patterns of Ca2+ mobilization.
      These studies illuminate the extent to which itpr1 molecular phenotype is induced
      by higher order RNA processing.

PMID- 15739178
TI  - Intracranial arterial dolichoectasia and small-vessel disease in stroke patients.
AB  - Two studies found that stroke patients with intracranial arterial dolichoectasia
      (IADE) had lacunar infarction more often than the control subjects. The relation
      between IADE and other manifestations of small-vessel disease (multilacunar
      state, leukoaraiosis, and etat crible) was not investigated. The magnetic
      resonance images of 510 patients with brain infarction in the Etude du Profil
      Genetique de l'Infarctus Cerebral (GENIC) study were evaluated for the diagnosis
      of multilacunar infarction (>1 lacunar infarct), leukoaraiosis (assessed in
      periventricular and subcortical regions according to Scheltens and colleagues'
      scale, with severe leukoaraiosis defined as a score > 8), etat crible (using a
      semiquantitative score ranging from 0-8, with severe EC > 4), and IADE (using the
      consensus method). By comparison with stroke patients without IADE (n = 447),
      IADE(+) stroke patients (n = 63) had significantly more frequent multilacunar
      state (51 vs 33%), severe leukoaraiosis (34 vs 19%), and severe etat crible (32
      vs 12%). After adjustment for potential confounding factors, the odds ratios (95%
      confidence interval) for the presence of IADE were 2.05 (1.08-3.87) for
      multilacunar state, 2.40 (1.11-5.20) for severe leukoaraiosis, and 3.60 (1.43
      9.08) for severe etat crible. The factors significantly associated with etat
      crible were older age and a familial history of stroke. IADE in stroke patients
      was independently associated with parenchymal manifestations of small-vessel
      disease. These conditions may have in common underlying pathophysiological
      processes.

PMID- 15739179
TI  - Monovalent cations affect the free solution mobility of DNA by perturbing the
      hydrogen-bonded structure of water.
AB  - The free solution mobilities of single- and double-stranded DNA molecules of
      various molecular weights have been measured by capillary electrophoresis in
      solutions of constant ionic strength containing a common anion and fifteen
      different monovalent cations. In solutions with the same ionic composition, the
      mobilities of different DNA molecules can vary by up to 20%, depending on
      molecular weight, the number of strands, and the presence or absence of A-tracts,
      runs of four or more contiguous adenine residues. Importantly, the mobilities
      observed for the same DNA sample can vary by up to 40% in solutions containing
      different cations. The mobility differences observed for the same DNA in
      solutions containing different cations cannot be rationalized by differences in
      the anhydrous radii or intrinsic conductivities of the various cations, or by the
      sequence-dependent binding of certain cations to A-tracts. Instead, the observed
      mobilities are linearly correlated with the average number of water-water
      hydrogen bonds that are present in solutions containing different cations. The
      mobilities are also correlated with the viscosity B coefficients of the various
      cations and with the rotational correlation times frictional coefficients
      observed for water molecules in solutions containing different cations. Hence,
      monovalent cations modify the free solution mobility of DNA primarily by
      perturbing the hydrogen-bonded structure of water, affecting the friction
      experienced by the migrating DNA molecules during electrophoresis.

PMID- 15739180
TI  - Does the anesthetic 2,2,2-trifluoroethanol interact with bovine serum albumin by
      direct binding or by solvent-mediated effects? A calorimetric and spectroscopic
      investigation.
AB  - Thermal unfolding of bovine serum albumin (BSA) has been studied in the presence
      of 2,2,2-trifluoroethanol (TFE) using high-sensitivity microdifferential scanning
      calorimetry. Quantitative thermodynamic parameters accompanying the thermal
      transitions have been evaluated. TFE is observed to be a stabilizer or a
      destabilizer of the folded state of BSA depending on the pH. CD spectroscopy
      revealed an increase in the alpha-helical content of BSA and a decrease in the
      tertiary structure in the presence of increasing molalities of TFE. Isothermal
      titration calorimetric results do not indicate appreciable binding of the TFE
      molecules to BSA. TFE quenches the steady-state tryptophan fluorescence of BSA
      only at higher molalities and there is no effect on the tryptophan fluorescence
      at lower molalities. The calorimetric and spectroscopic results obtained in this
      work suggest that solvent-mediated effects dominate the interaction of TFE with
      BSA and the binding component may be very weak. Since the binding component is
      very weak, one of the possibilities of anesthetic action of TFE molecules on the
      actual targets may be through perturbation of the structural and dynamic
      properties of the lipid bilayer so that the function of crucial but unspecified
      membrane proteins is affected.

PMID- 15739181
TI  - FT-IR spectrometry analysis of plasma fatty acyl moieties selective mobilization
      during endurance exercise.
AB  - This study was designed to describe changes in plasma fatty acyl moieties during
      a 2-h endurance exercise. Sixteen endurance-trained subjects cycled 2 h at 55% of
      maximal power output and capillary blood was sampled every 15 min. Fourier
      transform infrared (FT-IR) spectrometry was used to determine correlated changes
      between plasma fatty acyl moieties (FAM) structural characteristics and metabolic
      parameters (oxygen consumption, respiratory exchange ratio, glucose, lactate, TG,
      glycerol, and albumin). Opposite changes were found between carbohydrate and
      fatty acid metabolism during the second hour of exercise, i.e., a decrease of
      glucose and lactate concentrations while albumin, FAM, and TG increased. For
      fatty acid metabolism, FAM and TG did not showed the same pattern of changes at
      the end of exercise, i.e., TG remained constant after 90 min while FAM continued
      to increase. This late FAM concentration increase was correlated to the changes
      in albumin concentration and the nu C=C-H/nu(as) CH3 and nu(as) CH2/nu(as) CH3
      ratios. These ratios clearly showed that FAM unsaturation increased while chain
      length decreased. It was hypothesized that PUFA from TG adipose lipolysis ketone
      bodies (beta-hydroxybutyric acid) from liver may have been released in higher
      amounts as glycogen stores became depleted after 90 min of exercise.

PMID- 15739182
TI  - Analysis of structural change in keratin fibers resulting from chemical
      treatments using Raman spectroscopy.
AB  - In order to investigate the influence of chemical treatments (reduction, heating,
      and oxidation) on keratin fibers, the structure of virgin white human hair
      resulting from a permanent hair straightening process at various depths of cross
      sectional samples was directly analyzed without isolating the cuticle and cortex,
      using Raman spectroscopy. The band shape of the cuticle was different from that
      of the cortex, and the cuticle had a more amorphous structure, compared with the
      cortex. The S-S band intensity existing in the hair surface remarkably decreased,
      while the S-S band intensity in the hair center was not changed by performing the
      reduction process. In the case of heating the keratin fibers after the reduction
      process, this tendency was unchanged. On the other hand, the amide III
      (unordered) band intensity in the cortex region increased, indicating that
      proteins existing throughout the cortex region caused a change to the random coil
      form. Moreover, approximately 95% of the disconnected -SS- groups were clearly
      reconnected by performing the oxidation process after heating (the degree of
      reconnection of -SS- groups was about 90%, in the case of oxidizing after
      reduction). From these experiments, we concluded that the heat treatment process
      in the permanent hair straightening treatment caused the randomization of
      proteins existing throughout the cortex region, thereby contributing to the
      acceleration of the reconnection of -SS- groups during the oxidation process.

PMID- 15739183
TI  - 7-Ketocholesterol favors lipid accumulation and colocalizes with Nile Red
      positive cytoplasmic structures formed during 7-ketocholesterol-induced
      apoptosis: analysis by flow cytometry, FRET biphoton spectral imaging microscopy,
      and subcellular fractionation.
AB  - BACKGROUND: Oxidized low-density lipoproteins play key roles in atherosclerosis.
      Their toxicity is at least in part due to 7-ketocholesterol (7KC), which is a
      potent inducer of apoptosis. In this study on human promonocytic U937 cells, we
      determined the effects and the interactions of 7KC with cellular lipids during
      7KC-induced apoptosis. METHODS: Morphologic and functional changes were
      investigated by microscopic and flow cytometric methods after staining with
      propidium iodide, 3,3'-dihexyloxacarbocyanine iodide, and Hoechst 33342. Cellular
      lipid content was identified by using filipin to quantify free cholesterol and
      Nile Red (NR), which emit a yellow or orange-red fluorescence in the presence of
      neutral and polar lipids, respectively. After staining with NR, interactions of
      7KC with cellular lipids were identified by fluorescence resonance energy
      transfer biphoton spectral imaging confocal microscopy and by subcellular
      fractionation, gas chromatography, and mass spectrometry. RESULTS: During 7KC
      induced apoptosis the fluorescence from filipin and the ratio of measured (orange
      red vs. yellow) fluorescence of NR were enhanced. Spectral analysis of images
      obtained in biphoton mode and resulting factor images demonstrated the occurrence
      of fluorescence resonance energy transfer between 7KC and NR and the subsequent
      colocalization of 7KC and NR. These data were in agreement with biochemical
      characterization and demonstrated that 7KC and neutral and polar lipids
      accumulate in NR-stained cytoplasmic structures. CONCLUSIONS: During 7KC-induced
      apoptosis, 7KC modifies the cellular content of neutral and polar lipids, favors
      free cholesterol accumulation, and colocalizes with neutral and polar lipids that
      are inside NR-stained cytoplasmic structures.

PMID- 15739184
TI  - Novel polyelectrolyte carboxymethyl konjac glucomannan-chitosan nanoparticles for
      drug delivery. I. Physicochemical characterization of the carboxymethyl konjac
      glucomannan-chitosan nanoparticles.
AB  - Carboxymethyl konjac glucomannan-chitosan (CKGM-CS) nanoparticles, which are well
      dispersed and stable in aqueous solution, were spontaneously prepared under very
      mild conditions via polyelectrolyte complexation. The physicochemical properties
      of the nanoparticles were identified by Zetasizer 3000 and Fourier transform
      infrared. It was found that at various CKGM and CS concentrations the particles
      ranged in size from approximately 50 to 1200 nm, and the zeta potential from 15
      to 45 mV. By changing pH value of the medium and increasing the concentration of
      salt, the mean size of the particles increased and the zeta potential decreased.
      Also, investigations on the encapsulation efficiency of the bovine serum albumin
      loaded CKGM-CS nanoparticles were also undertaken. This nanoparticulate system
      driven by complex formation shows potential as an advanced drug delivery system
      for water-soluble drugs.

PMID- 15739185
TI  - Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a
      rat model of HCC.
AB  - Hepatocellular carcinoma (HCC) is regarded as a suitable target for
      antiangiogenic strategies. However, antiangiogenic agents aimed at single targets
      can be neutralized by upregulation of other proangiogenic factors. Therefore,
      combined approaches addressing at least two angiogenic targets should be more
      effective. Employing an appropriate rat hepatoma model, we examined the effects
      of sFlt-1 (soluble vascular endothelial growth factor [VEGF] receptor 1 as an
      indirect inhibitor of angiogenesis) and endostatin (a direct inhibitor of
      angiogenesis) in both single-agent as well as combined approaches under in vitro
      and in vivo conditions. Similar to human HCC, rat Morris hepatoma (MH) cells
      secreted high levels of VEGF, but no endogenous sFlt-1. Parental MH or MHES(r)
      cells, stably expressing rat endostatin, were adenovirally transduced either with
      AdsFlt-1 (encoding sFlt-1) or control vector Adnull (containing no transgene),
      followed by subcutaneous inoculation into syngeneic ACI rats. Compared with
      MH/Adnull cells, expressing no antiangiogenic factors at all, tumor weights were
      reduced fourfold in the MHES(r)/Adnull group, 19-fold in the MH/AdsFlt-1-group,
      and 77-fold in the MHES(r)/AdsFlt-1 combination therapy group. Analysis of
      variance did not show a significant interaction between the effects of the two
      factors ES(r) and sFlt-1; their effects multiplied. In conclusion, combined
      expression of sFlt-1 and endostatin effectively suppresses HCC growth under in
      vivo conditions. Supplementary material for this article can be found on the
      HEPATOLOGY website (http://interscience.wiley.com/jpages/0270
      9139/suppmat/index.html).

PMID- 15739186
TI  - Are seeds suitable for flow cytometric estimation of plant genome size?
AB  - BACKGROUND: Nuclear DNA content in plants is commonly estimated using flow
      cytometry (FCM). Plant material suitable for FCM measurement should contain the
      majority of its cells arrested in the G0/G1 phase of the cell cycle. Usually
      young, rapidly growing leaves are used for analysis. However, in some cases seeds
      would be more convenient because they can be easily transported and analyzed
      without the delays and additional costs required to raise seedlings. Using seeds
      would be particularly suitable for species that contain leaf cytosol compounds
      affecting fluorochrome accessibility to the DNA. Therefore, the usefulness of
      seeds or their specific tissues for FCM genome size estimation was investigated,
      and the results are presented here. METHODS: The genome size of six plant species
      was determined by FCM using intercalating fluorochrome propidium iodide for
      staining isolated nuclei. Young leaves and different seed tissues were used as
      experimental material. Pisum sativum cv. Set (2C = 9.11 pg) was used as an
      internal standard. For isolation of nuclei from species containing compounds that
      interfere with propidium iodide intercalation and/or fluorescence, buffers were
      used supplemented with reductants. RESULTS: For Anethum graveolens, Beta
      vulgaris, and Zea mays, cytometrically estimated genome size was the same in
      seeds and leaves. For Helianthus annuus, different values for DNA amounts in
      seeds and in leaves were obtained when using all but one of four nuclei isolation
      buffers. For Brassica napus var. oleifera, none of the applied nuclei isolation
      buffers eliminated differences in genome size determined in the seeds and leaves.
      CONCLUSIONS: The genome size of species that do not contain compounds that
      influence fluorochrome accessibility appears to be the same when estimated using
      specific seed tissues and young leaves. Seeds can be more suitable than leaves,
      especially for species containing staining inhibitors in the leaf cytosol. Thus,
      use of seeds for FCM nuclear DNA content estimation is recommended, although for
      some species a specific seed tissue (usually the radicle) should be used.
      Protocols for preparation of samples from endospermic and endospermless seeds
      have been developed.

PMID- 15739187
TI  - Progressive arthropathy in mice with a targeted disruption of the Mop3/Bmal-1
      locus.
AB  - Disruption of the murine Mop3 (also known as Bmal1 or Arntl) locus results in a
      loss of behavioral and molecular circadian rhythms. Although Mop3 null mice do
      not display anomalies in early development, they do display reduced activity as
      they age. In an effort to explain this decreased activity, we characterized the
      physiological and anatomical changes that occurred with age. We observed that
      Mop3 null mice display an increased mortality after 26 weeks of age and a
      phenotype best described as a progressive noninflammatory arthropathy. Although
      little pathology is observed prior to 11 weeks of age, by 35 weeks of age
      essentially all Mop3 null animals develop joint ankylosis due to flowing
      ossification of ligaments and tendons and almost complete immobilization of
      weight-bearing and nonweight-bearing joints. This pathology appears to explain
      the decreased activity of Mop3 null mice and suggests that MOP3 is an inhibitor
      of ligament and tendon ossification.

PMID- 15739188
TI  - c-Jun N-terminal kinases (JNKs) mediate pro-inflammatory actions of microglia.
AB  - The activation and function of c-Jun N-terminal kinases (JNKs) were investigated
      in primary microglia cultures from neonatal rat brain, which express all three
      JNK isoforms. Lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha),
      and thrombin preparations induced a rapid and lasting activation of JNKs in the
      cytoplasm. In the nucleus, the activation patterns were rather complex. In
      untreated microglia, the small pool of nuclear JNKs was strongly activated, while
      the high-affinity JNK substrate c-Jun was only weakly phosphorylated. Stimulation
      with LPS increased the total amount of nuclear JNKs and the phosphorylation of
      the transcription factor c-Jun. Levels of activated JNKs in the nucleus, however,
      rapidly decreased. Analysis of the nuclear JNK isoforms revealed that the amount
      of JNK1 declined, while JNK2 increased, and the weakly expressed JNK3 did not
      vary. This observation suggests that JNK2 is mainly responsible for the
      activation of c-Jun in this context. Upstream of JNKs, LPS induced a lasting
      activation of the constitutively present JNK kinase MKK4. The function of JNKs in
      LPS-triggered cellular reactions was investigated using SP600125 (0.5-5 microM),
      a direct inhibitor of JNKs. Inhibition of JNKs reduced the LPS-induced metabolic
      activity and induction of the AP-1 target genes cyclooxygenase-2 (Cox-2), TNF
      alpha, monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in
      response to LPS, while ERK1/2 and p38 alpha had a more pronounced effect on LPS
      induced cellular enlargement than JNKs. In summary, JNKs are essential mediators
      of relevant pro-inflammatory functions in microglia with different contributions
      of the JNK isoforms.

PMID- 15739189
TI  - Cell proliferation and replacement following contusive spinal cord injury.
AB  - After spinal cord injury (SCI), about 50% of the oligodendrocytes and astrocytes
      in the residual white matter at the injury site are lost by 24 h. However,
      chronically after SCI, the density of oligodendrocytes is normal. Previous
      studies have shown that the adult rat spinal cord contains a pool of
      proliferating glial progenitors whose progeny could help restore cell density
      after injury. To study proliferation in response to injury, we performed SCI on
      adult female rats at the T8 level, using a standardized contusion model. Animals
      received bromodeoxyuridine (BrdU) injections during the first week after SCI, and
      were perfused within 2 h for acute studies, and at 6 weeks for chronic studies.
      The tissue was analyzed using immunohistochemical detection of BrdU and cell
      marker antigens. We demonstrate that cell proliferation in the residual white
      matter is increased at 1-7 days after SCI, peaking on day 3. Dividing cells
      include oligodendrocytes, astrocytes, microglia/macrophages, and a high
      proportion of NG2(+) glial precursors. By 6 weeks, some cells that had been
      labeled 2-4 days after SCI were still present. Double immunohistochemistry showed
      that while very few of these cells expressed NG2 or the microglia/macrophage
      marker OX42, about 50% expressed CC1 or glial fibrillary acidic protein (GFAP),
      markers of mature oligodendrocytes and astrocytes, respectively. The post-injury
      environment represented by residual white matter is thus permissive to the
      differentiation of glial precursors. Cells that are stimulated to divide during
      the first week after SCI develop chronically into mature phenotypes that replace
      macroglia lost after injury.

PMID- 15739190
TI  - Pigment epithelium-derived factor induces pro-inflammatory genes in neonatal
      astrocytes through activation of NF-kappa B and CREB.
AB  - Pigment epithelium-derived factor (PEDF) is a potent and broadly acting
      neurotrophic factor that protects neurons in various types of cultured neurons
      against glutamate excitotoxicity and induced-apoptosis. Some of the effects of
      PEDF reflect specific changes in gene expression, mediated via activation of the
      transcription factor NF-kappa B in neurons. To investigate whether PEDF also
      modulates gene expression in astrocytes, we employed the use of RT-PCR to analyze
      the gene expression of certain pro-inflammatory genes and found that genes such
      as IL-1 beta, IL-6, TNF-alpha, MIP1 alpha, and MIP3 alpha were induced in PEDF
      treated cultured neonatal astrocytes, but not in adult astrocytes.
      Electrophoresis mobility shift assay (EMSA) revealed that a time- and dose
      dependent increase of NF-kappa B- and AP-1-DNA binding activity was observed in
      PEDF-treated neonatal astrocytes. Furthermore, rapid phosphorylation of CREB
      protein had occurred in PEDF-treated neonatal astrocytes. Upregulation of pro
      inflammatory and AP-1-related genes by PEDF was blocked by overexpression of
      dominant negative CREB or a mutated form of I kappa B alpha. These results
      suggest that the induction of pro-inflammatory genes is mediated via activation
      of NF-kappa B, AP-1, and CREB in neonatal astrocytes. Taken together, these
      results demonstrate that PEDF is a multipotent factor, capable of affecting not
      only neurons, but also neonatal astrocytes, and suggests that it may act as a
      neuroimmune modulator in the developmental brain.

PMID- 15739191
TI  - Clozapine reduces GLT-1 expression and glutamate uptake in astrocyte cultures.
AB  - To test the hypothesis that clozapine-induced reduction of glutamate transporter
      1 (GLT-1) expression is mediated by astrocytes, we studied the effects of
      clozapine on Glu transporters and Glu uptake in primary astrocyte cultures of the
      cerebral cortex. Astrocyte cultures treated for 48 h with clozapine exhibited a
      reduction in GLT-1 levels of about 50%, whereas glutamate-aspartate transporter
      (GLAST) levels remained unchanged. Glu uptake was also lowered, and this
      reduction was dose-dependent. Our findings indicate that clozapine reduces GLT-1
      expression and function by a mechanism that directly involves astrocytes. A
      better understanding of the molecular events by which antipsychotics regulate Glu
      uptake can contribute to identify new targets for the treatment of schizophrenia.

PMID- 15739192
TI  - Theoretical insights into the mechanism of acetylcholinesterase-catalyzed
      acylation of acetylcholine.
AB  - Acylation of acetylcholine (ACh) catalyzed by acetylcholinesterase (AChE) has
      been studied using high-level theoretical calculations on a model system that
      mimics the reaction center of the enzyme, and compared with uncatalyzed acylation
      reaction. The geometries of all the intermediates and transition states,
      activation energies, and solvent effects have been calculated. The calculations
      predict simultaneous formation of two short-strong hydrogen bonds (SSHB) in the
      rate-determining transition state structures [the first SSHB involves the
      hydrogen atom of Ser-200 (H(s)) and another involves the hydrogen atom of His-440
      (H(h))]. In the intermediate states, the H-bond corresponding to H(h) involves
      SSHB, whereas the one corresponding to H(s) does not.

PMID- 15739193
TI  - The OH* + CH3SH reaction: support for an addition-elimination mechanism from ab
      initio calculations.
AB  - Several intermediates for the CH(3)SH + OH(*) --> CH(3)S(*) + H(2)O reaction were
      identified using MP2(full) 6-311+g(2df,p) ab initio calculations. An adduct,
      CH(3)S(H)OH(*), I, with electronic energy 13.63 kJ mol(-1) lower than the
      reactants, and a transition state, II(double dagger), located 5.14 kJ mol(-1)
      above I, are identified as the entrance channel for an addition-elimination
      reaction mechanism. After adding zero-point and thermal energies, DeltaH(r,298) (
      degrees )(reactants --> I) = -4.85 kJ mol(-1) and DeltaH(298) (double dagger)(I -
      > II(double dagger)) = +0.10 kJ mol(-1), which indicates that the potential
      energy surface is broad and flat near the transition state. The calculated
      imaginary vibrational frequency of the transition state, 62i cm(-1), is also
      consistent with an addition-elimination mechanism. These calculations are
      consistent with experimental observations of the OH(*) + CH(3)SH reaction that
      favored an addition-elimination mechanism rather than direct hydrogen atom
      abstraction. An alternative reaction, CH(3)SH + OH(*) --> CH(3)SOH + H(*), with
      DeltaH(r,298) ( degrees ) = +56.94 kJ mol(-1) was also studied, leading to a
      determination of DeltaH(f,298) ( degrees )(CH(3)SOH) = -149.8 kJ mol(-1).

PMID- 15739194
TI  - Magic number silicon dioxide-based clusters: laser ablation-mass spectrometric
      and density functional theory studies.
AB  - The magic number silica clusters [(SiO(2))(n)O(2)H(3)](-) with n = 4 and 8 have
      been observed in the XeCl excimer laser (308 nm) ablation of various porous
      siliceous materials. The structural origin of the magic number clusters has been
      studied by the density functional theoretical calculation at the B3LYP/6-31G**
      level, with a genetic algorithm as a supplementary tool for global structure
      searching. The DFT results of the first magic number cluster are parallel to the
      corresponding Hartree-Fock results previously reported with only small
      differences in the structural parameters. Theoretical calculation predicts that
      the first magic number cluster (SiO(2))(4)O(2)H(4) and its anion
      [(SiO(2))(4)O(2)H(3)](-) will most probably take pseudotetrahedral cage-like
      structures. To study the structural properties of the second magic number
      cluster, geometries of the bare cluster (SiO(2))(8), the neutral complex cluster
      (SiO(2))(8)O(2)H(4), and the anionic cluster [(SiO(2))(8)O(2)H(3)](-) are fully
      optimized at the B3LYP/6-31G** level, and the corresponding vibrational
      frequencies are calculated. The DFT calculations predict that the ground state of
      the bare silica octamer (SiO(2))(8) has a linear chain structure, whereas the
      second magic number complex cluster (SiO(2))(8)O(2)H(4) and its anion
      [(SiO(2))(8)O(2)H(3)](-) are most probably a mixture of cubic cage-like
      structural isomers with an O atom inside the cage and several quasi-bicage
      isomers with high intercage interactions. The stabilization of these structures
      can also be attributed to the active participation of the group of atoms 2O and
      4H (3H for the anion) in chemical bonding during cluster formation. Our
      theoretical calculation gives preliminary structural interpretation of the
      presence of the first and second magic number clusters and the absence of higher
      magic numbers.

PMID- 15739195
TI  - Accuracy and efficiency of atomic basis set methods versus plane wave
      calculations with ultrasoft pseudopotentials for DNA base molecules.
AB  - Recent results from Preuss et al. (J Comput Chem 2004, 25, 112) on DNA base
      molecules, obtained by plane wave density functional calculations using ultrasoft
      pseudopotentials, are compared with calculations using Gaussian basis sets. Bond
      lengths and angles agree closely, but dihedral angles and vibrational frequencies
      show significant differences. The Gaussian basis calculations are at least an
      order of magnitude more efficient than the plane wave/ultrasoft pseudopotential
      calculations at a similar level of accuracy; the advantage is even larger if the
      Fourier Transform Coulomb method is used. To obtain definite benchmark values,
      the geometries of the four DNA bases were optimized at the MP2 level with large
      basis sets, up to cc-pVQZ and aug-cc-pVTZ.

PMID- 15739196
TI  - Metastasis--an alternative hypothesis.
AB  - The currently accepted models of metastasis are inconsistent with many clinical
      observations of the natural history of cancer and its response to therapy.
      Specifically, the authors suggest that it is time for a "paradigm shift." It is
      time to reject the "local, regional, systemic hypothesis" of cancer and replace
      it with a hypothesis more consistent with the clinical facts, specifically, that
      cancer exists in many different forms (i.e. localized disease arising from
      locally acting carcinogens, which can spread locally and should be treated
      locally, and cancer that arises as localized disease but evolves to more
      malignant invasive disease [the current model of metastasis]). The other forms of
      cancer are systemic disease, which is induced by systemic carcinogens, and cancer
      arising in multiple cells and multiple sites, giving rise to a picture described
      as metastatic cancer. The importance of this paradigm shift is that more
      attention would be focused on identifying systemically acting carcinogens as they
      relate to etiology and to molecular abnormalities in the neoplastic cells that
      might be targeted clinically. Recent advances in cancer treatment have
      demonstrated that molecules that target cancer cell molecular abnormalities
      (rather than tissue of origin, lymph node, or metastasis) such as bcr-abl or
      mutations in a cellular receptor such as c-kit or epidermal growth factor possess
      curative potential. In addition, more attention should be devoted to
      distinguishing between local tumors and systemic disease, using sophisticated
      molecular biologic techniques. Perhaps most important, there is a need to devise
      therapeutic strategies that would treat cancer as a systemic illness and
      hopefully have a substantial impact on overall cancer mortality.

PMID- 15739198
TI  - 1-alkoxyvinyl esters: renaissance of half-century-old acyl donors with potential
      applicability.
AB  - Among the various kinds of acyl donors, the 1-alkoxyvinyl esters have
      characteristic features, such as a high reactivity under nearly neutral
      conditions and the generation of neutral and volatile esters as single
      coproducts. Although their use in organic syntheses began in the middle of the
      1950s, no significant progress has been seen. This is probably because the
      existing method of preparing alkoxyvinyl esters used toxic mercuric salts and was
      not totally applicable for those esters having functionalized acyl moieties. We
      have discovered that the use of a catalytic amount of the less toxic [RuCl2(p
      cymene)]2 effectively accelerates the addition of carboxylic acids to
      ethoxyacetylene to give ethoxyvinyl esters bearing a variety of functionalized
      acyl groups in high yields. This discovery has opened a new avenue for developing
      new reactions and new synthetic methodologies based on the design and use of
      these acyl donors with suitable functional groups. Such examples include (i) the
      installation of hydrophilic acyl moieties on biologically active compounds, (ii)
      asymmetric Pummerer-type reactions, (iii) aromatic Pummerer-type reactions, (iv)
      the lipase-catalyzed desymmetrization of symmetrical 1,3-diols, and (v) lipase
      catalyzed domino reactions. Future possibilities for these acyl donors are also
      discussed.

PMID- 15739199
TI  - Development of apatite-type oxide ion conductors.
AB  - Research into materials displaying oxide ion conductivity is attracting
      considerable attention due to their potential technological applications in
      devices such as Solid Oxide Fuel Cells. In this paper, recent work on apatite
      type oxide ion conductors is reviewed, showing that a wide range of cation
      substitutions are possible, due to the flexibility of the apatite structure in
      accommodating a range of ion sizes. The conductivity studies on these doped
      samples show that to achieve high oxide ion conduction, non-stoichiometry in
      terms of cation vacancies and/or oxygen excess is required, with the latter
      resulting in the highest conductivities. In contrast to most common oxide ion
      conductors, e.g. perovskite and fluorite in which oxide ion conduction proceeds
      via oxygen vacancies, the research on these apatite systems suggests that the
      conductivity involves interstitial oxide ions. With further optimization of these
      materials, particularly in terms of the Ge-containing systems, significant
      improvements in conductivity are likely, leading to the very real possibility of
      the application of apatite-type electrolytes in fuel cell and other applications.

PMID- 15739197
TI  - A possible association of Pro12Ala polymorphism in peroxisome proliferator
      activated receptor gamma2 gene with obesity in native Javanese in Indonesia.
AB  - BACKGROUND: Peroxisome proliferators-activated receptor gamma (PPAR gamma) is a
      nuclear hormone receptor that serves as a master regulator of adipocytes-specific
      genes contributing to adipocytes differentiation, susceptibility to obesity, and
      insulin sensitivity. The substitution of proline to alanine at codon 12 of the
      PPAR gamma2 gene (Pro12Ala polymorphism) is most frequently identified and the
      associations with diabetes, obesity, and other clinical parameters have been
      reported and discussed in several ethnic groups. Among native Javanese ethnicity,
      however, there is no report about this polymorphism. AIMS AND METHODS: Aims of
      this study were to estimate the allele frequency of the Pro12Ala polymorphism of
      PPAR gamma2 gene among native Javanese in Indonesia and to investigate the
      relationship between this polymorphism and obesity or diabetes. This study
      included 540 native Javanese subjects consisting of 337 diabetic patients and 203
      normal glucose tolerance subjects. Both groups included totally 160 obese
      subjects (body mass index > or = 25 kg/m(2)). PCR-restriction fragment length
      polymorphism was used for the genotype determination. RESULTS: The allele
      frequency of Pro12Ala polymorphism in PPAR gamma2 gene among native Javanese is
      lower than that in other ethnic groups. No association is seen between the
      Pro12Ala and diabetes (0.01 vs 0.017%, p = 0.404), a trend of the higher BMI was
      observed in Pro12Ala carriers in nondiabetic subjects, although this association
      is limited by small numbers. CONCLUSION: In this study, no association is seen
      between the Pro12Ala polymorphism in PPAR gamma2 gene and diabetes; a weak
      association with obesity is seen.

PMID- 15739200
TI  - Preparation of murine B7.1-glycosylphosphatidylinositol and transmembrane
      anchored staphylococcal enterotoxin. A dual-anchored tumor cell vaccine and its
      antitumor effect.
AB  - BACKGROUND: The authors have previously reported a tumor cell vaccine modified
      with superantigen staphylococcal enterotoxin A (SEA) and its antitumor effect.
      The tumor cell vaccines modified with multiple immune activators frequently
      elicited stronger immune responses against established tumors than single
      modified vaccines. METHODS: The authors explored the effectiveness of a tumor
      cell vaccine transduced with immune activators, dual-modified using the protein
      transfer technique. First, a glycosylphosphatidylinositol (GPI)-anchored murine
      B7.1 (mB7.1-GPI) and a transmembrane-anchored SEA (TM-SEA) were genetically
      generated. Then, the murine lymphoma EL4 cells were dual modified with the
      incorporation of mB7.1-GPI and TM-SEA onto the cell surface. Flow cytometry and
      laser confocal microscopy showed that the incorporation of B7.1 and SEA molecules
      onto EL4 cells was quite stable. RESULTS: The dual-modified tumor cell vaccine
      EL4/mB7.1-GPI + TM-SEA elicited significantly stronger antitumor immune responses
      both in vitro and in vivo when compared with the single-modified tumor cell
      vaccines EL4/mB7.1-GPI and EL4/TM-SEA. CONCLUSIONS: The results of the current
      study validated the novel approach for preparing tumor cell vaccines modified
      with dual immune active molecules using the protein transfer technique, and
      supported the feasibility and effectiveness of the dual-modified tumor cell
      vaccine.

PMID- 15739202
TI  - One gene, two diseases and three conformations: molecular dynamics simulations of
      mutants of human prion protein at room temperature and elevated temperatures.
AB  - Fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD) are associated
      to the same mutation at codon 178 but differentiate into clinicopathologically
      distinct diseases determined by this mutation and a naturally occurring
      methionine-valine polymorphism at codon 129 of the prion protein gene. It has
      been suggested that the clinical and pathological difference between FFI and CJD
      is caused by different conformations of the prion protein. Using molecular
      dynamics (MD), we investigated the effect of the mutation at codon 178 and the
      polymorphism at codon 129 on prion protein dynamics and conformation at normal
      and elevated temperatures. Four model structures were examined with a focus on
      their dynamics and conformational changes. The results showed differences in
      stability and dynamics between polymorphic variants. Methionine variants
      demonstrated a higher stability than valine variants. Elongation of existing beta
      sheets and formation of new beta-sheets was found to occur more readily in valine
      polymorphic variants. We also discovered the inhibitory effect of proline residue
      on existing beta-sheet elongation.

PMID- 15739201
TI  - Geranylgeranylacetone inhibits lysophosphatidic acid-induced invasion of human
      ovarian carcinoma cells in vitro.
AB  - BACKGROUND: Lysophosphatidic acid (LPA) induced a dose-dependent increase of
      cancer cell invasion by promoting Rho/Rho-associated kinase signaling.
      Prenylation of Rho is essential for regulating cell growth, motility, and
      invasion. Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically
      as an antiulcer drug. Recent findings suggested that GGA might inhibit the small
      GTPase activation by suppressing prenylation. The authors hypothesized that the
      anticancer effects of GGA result from the inhibition of Rho activation. METHODS:
      The authors examined the effect of GGA using an in vitro invasion assay in human
      ovarian carcinoma cells, and analyzed the mechanism of the GGA effect on Rho
      activation, stress fiber formation and focal adhesion assembly, which are
      essential processes for cell invasion. RESULTS: The induction of ovarian
      carcinoma cell invasion by LPA was inhibited by the addition of GGA in a dose
      dependent manner. Treatment of cancer cells with GGA resulted in inactivation of
      Rho, changes in cell morphology, loss of stress fiber formation and focal
      adhesion assembly, and the suppression of tyrosine phosphorylation of focal
      adhesion proteins. The effect of GGA on cancer cells was partially prevented by
      the addition of geranylgeraniol, which is an intermediate of geranylgeranyl
      pyrophosphate and compensates geranylgeranylation of Rho. CONCLUSIONS: The
      inhibition of LPA-induced invasion by GGA was, at least in part, derived from
      suppressed Rho activation by preventing geranylgeranylation.

PMID- 15739203
TI  - Creation of highly functional thin films using electrochemical nanotechnology.
AB  - This overview describes the results of our recent study of the application of
      electrochemical nanotechnology to the fabrication of magnetic recording
      materials, interconnects in ultra-large-scale integrated (ULSI) devices, energy
      storage materials, and on-chip biosensors. It is important to note that
      electrochemical processes play significant roles in developing and fabrication
      such sophisticated materials and devices. In the field of magnetic recording,
      electrodeposition methods for preparing CoNiFe and CoFe soft magnetic thin films
      with a high saturation magnetic flux density were newly developed, and the
      significant issues for obtaining those films are highlighted. In the area of ULSI
      interconnects, we developed a technique using a self-assembled monolayer (SAM)
      for direct bonding of the interconnect layer to SiO2, and proposed a novel
      electroless deposition method for fabricating a diffusion barrier layer. In the
      field of batteries, electrodeposited SnNi alloy was proposed as a future anode
      material for Li batteries, and electrochemical MEMS processes were shown to be
      useful for fabricating micro-sized direct methanol fuel cells (DMFCs) as portable
      batteries for electronics applications. In the area of chemical sensors, we
      developed a new process for fabricating field effect transistors (FETs) modified
      with SAMs for on-chip biosensing applications.

PMID- 15739204
TI  - Statistical criteria for the identification of protein active sites using
      Theoretical Microscopic Titration Curves.
AB  - Theoretical Microscopic Titration Curves (THEMATICS) may be used to identify
      chemically important residues in active sites of enzymes by characteristic
      deviations from the normal, sigmoidal Henderson-Hasselbalch titration behavior.
      Clusters of such deviant residues in physical proximity constitute reliable
      predictors of the location of the active site. Originally the residues with
      deviant predicted behavior were identified by human observation of the computed
      titration curves. However, it is preferable to select the unusual residues by
      mathematically well-defined criteria, in order to reduce the chance of error,
      eliminate any possible biases, and substantially speed up the selection process.
      Here we present some simple statistical tests that constitute such selection
      criteria. The first derivatives of the predicted titration curves resemble
      distribution functions and are normalized. The moments of these first derivative
      functions are computed. It is shown that the third and fourth moments, measures
      of asymmetry and kurtosis, respectively, are good measures of the deviations from
      normal behavior. Results are presented for 44 different enzymes. Detailed results
      are given for 4 enzymes with 4 different types of chemistry: arginine kinase from
      Limulus polyphemus (horseshoe crab); beta-lactamase from Escherichia coli;
      glutamate racemase from Aquifex pyrophilus; and 3-isopropylmalate dehydrogenase
      from Thiobacillus ferrooxidans. The relationship between the statistical measures
      of nonsigmoidal behavior in the predicted titration curves and the catalytic
      activity of the residue is discussed.

PMID- 15739205
TI  - Comparative structural analysis of TonB-dependent outer membrane transporters:
      implications for the transport cycle.
AB  - TonB-dependent outer membrane transporters (TBDTs) transport organometallic
      substrates across the outer membranes of Gram-negative bacteria. Currently,
      structures of four different TBDTs have been determined by X-ray crystallography.
      TBDT structures consist of a 22-stranded beta-barrel enclosing a hatch domain.
      Structure-based sequence alignment of these four TBDTs indicates the presence of
      highly conserved motifs in both the hatch and barrel domains. The conserved
      motifs of the two domains are always in close proximity to each other and
      interact. We analyzed the very large interfaces between the barrel and hatch
      domains of TBDTs and compared their properties to those of other protein-protein
      interfaces. These interfaces are extensively hydrated. Most of the interfacial
      waters form hydrogen bonds to either the barrel or the hatch domain, with the
      remainder functioning as bridging waters in the interface. The hatch/barrel
      interfacial properties most resemble those of obligate transient protein
      complexes, suggesting that the interface is conducive to conformational change
      and/or movement of the hatch within the barrel. These results indicate that TBDTs
      can readily accommodate substantial conformational change and movement of their
      hatch domains during the active transport cycle. Also, these structural changes
      may require only modest forces exerted by the energy-coupling TonB protein upon
      the transporter.

PMID- 15739206
TI  - Disturbed root development of permanent teeth after pediatric stem cell
      transplantation. Dental root development after SCT.
AB  - BACKGROUND: Deficient dental root development has been reported after
      conventional pediatric anticancer therapy, but less information is available on
      stem cell transplantation (SCT) recipients. METHODS: Root-crown (R/C) ratios of
      fully developed permanent teeth were assessed from panoramic radiographs of 52
      SCT recipients, who were treated when they were age < 10 years. Using standard
      deviation scores (SDSs), the authors compared the R/C ratios to the corresponding
      tooth and gender-specific values in a healthy population. The percentage of
      affected R/C ratios per individual was examined in a subgroup of 39 (SG39)
      patients with advanced tooth development. The effects of total body irradiation
      (TBI) and SCT age on the R/C ratios were studied in TBI and high-dose
      chemotherapy (HDC = non-TBI) groups and in 3 age groups (< or = 3.0 years, 3.1
      5.0 years, > or = 5.1 years). RESULTS: Per individual, 77% of the fully developed
      permanent teeth were affected in SG39. At the tooth level, in 77% of the 945
      teeth studied (52 patients), the R/C ratios were outside +/-2 SDSs. More teeth
      were affected in the TBI (85%) than in the non-TBI (55%) group (P < 0.001). The
      teeth of the patients who were ages 3.1-5.0 years old at SCT presented with the
      most severe aberrations of the R/C ratio (mean SDS = -4.4) whereas the teeth of
      the youngest (age < or = 3.0 years) and the oldest (age > or = 5.1 years)
      patients were equally affected (mean SDSs = -3.1 and -3.0, respectively).
      CONCLUSIONS: Disturbances of dental root growth always followed pediatric SCT.
      HDC alone intensely harmed root growth but TBI further increased the adverse
      effects that were most extensive in the patients 3.1-5.0 years at SCT. These
      sequelae should be taken into account during the lifelong dental follow-up to
      minimize the clinical consequences of dental injuries.

PMID- 15739207
TI  - Estimated impact of the Prostate Cancer Prevention Trial on population mortality.
AB  - BACKGROUND: The potential public health impact of the recently completed Prostate
      Cancer Prevention Trial (PCPT) is debated. The results indicated that the period
      prevalence of prostate cancer was reduced by 24.8% due to finasteride, whereas an
      increase in the rate of high-grade tumors (Gleason score 8-10) among men who were
      diagnosed with cancer also was found (5.0% in the PCPT placebo arm vs. 11.9% in
      the PCPT finasteride arm). Whether the increased Gleason score was valid or was a
      histologic artifact is under investigation. METHODS: The authors estimated the
      number of person-years saved assuming a 24.8% reduction in the incidence of
      prostate cancer for 5 years among United States males age > or = 55 years.
      Scenarios for different proportions of patients with high-grade Gleason scores
      also were considered. RESULTS: With a 24.8% reduction in the number of men with
      newly diagnosed prostate cancer, the authors estimated that 316,760 person-years
      would be saved due to finasteride in the United States. An absolute increase of
      6.9% in the proportion of men with high-grade tumors in the United States cancer
      population (corresponding to the difference between the rates on the placebo and
      finasteride arms of the PCPT) would reduce the number of person-years saved to
      262,567. For each absolute increase of 5% in the proportion of patients with high
      grade tumors, the number of person-years saved would be reduced by approximately
      39,000. CONCLUSIONS: The results of the PCPT may have a major impact on
      population mortality from prostate cancer if they are applied clinically. The
      potential detrimental effects of an increased rate of patients who have prostate
      cancer with high-grade Gleason scores would be outweighed by a reduction in
      incidence.

PMID- 15739208
TI  - A multicenter Phase II study of bortezomib in recurrent or metastatic sarcomas.
AB  - BACKGROUND: Based on evidence of activity in preclinical and Phase I studies, the
      authors undertook a study of bortezomib, a reversible proteasome inhibitor, for
      patients with metastatic sarcomas. METHODS: Two arms were opened, each using a
      Simon two-stage design. Arm A included patients with osteogenic sarcoma, Ewing
      sarcoma, and rhabdomyosarcoma. Arm B accrued patients with other types of soft
      tissue sarcomas. Patients were not allowed to have received previous chemotherapy
      for metastatic disease. The initial dose of bortezomib was a 1.5 mg/m2
      intravenous push twice weekly followed by a rest week. The dose was escalated to
      1.7 mg/m2 if patients tolerated Cycle 1 well. The dose escalation was eliminated
      due to toxicity observed in the first six patients. RESULTS: Painful neuropathy,
      myalgias, and asthenia were the most significant observed toxicities. The most
      frequent toxicities included fatigue, diarrhea, constipation, and nausea.
      Pharmacodynamic data from 18 patients with complete data collection did not show
      consistent differences between patients with or without Grade 2 or Grade 3
      neuropathy (toxicity graded according the National Cancer Institute Common
      Toxicity Criteria). Arm A had low accrual and was closed. One confirmed partial
      response among 21 evaluable patients was observed on Arm B in a patient with
      leiomyosarcoma. Due to the inactivity of this agent, the study was closed after
      the first stage of accrual. CONCLUSIONS: Bortezomib has minimal activity in soft
      tissue sarcoma as a single agent. If studied further in sarcomas, bortezomib
      should be investigated in combination with agents with demonstrated preclinical
      synergy.

PMID- 15739209
TI  - Osteosarcoma of the pelvis in children and young adults: the St. Jude Children's
      Research Hospital experience.
AB  - BACKGROUND: Pelvic osteosarcomas are difficult to resect. The authors reviewed
      their institution's experience with patients who had such tumors to characterize
      the patients' clinical findings and to assess the impact of surgical resection on
      outcome. METHODS: A review was conducted of the records from patients with pelvic
      osteosarcoma who were treated at the authors' institution between January, 1970
      and March, 2004. RESULTS: Among 442 patients with osteosarcoma, 19 patients (4%)
      had high-grade tumors arising in the pelvic bones, including the ilium in 15
      patients, the pubis in 2 patients, and the sacrum in 2 patients. The median
      patient age at diagnosis was 16.8 years. Four tumors were secondary to radiation
      therapy. Five patients had metastases in the lung (n = 4 patients) or bone (n = 1
      patient) at diagnosis. Ten tumors were chondroblastic. The median greatest tumor
      dimension for the 13 tumors with known size was 10 cm. Ten patients had
      unresectable pelvic tumors, and 9 patients underwent hemipelvectomy (2 internal
      and 7 external); complete resection with negative margins was achieved in 5
      patients. Four patients survived, including one patient who survived with
      disease. Of the three patients who survived disease-free, one patient underwent
      complete resection, one patient underwent incomplete resection (nonviable tumor
      at the soft tissue margin) with a good response to chemotherapy, and one patient
      with a sacral tumor underwent radiotherapy only for local control. Of the 9
      patients who underwent resection, 7 experienced disease recurrence (n = 5
      patients) or progression (n = 2 patients) at distant sites and died. All patients
      with metastatic disease at diagnosis died. CONCLUSIONS: Pelvic osteosarcomas
      often were large and unresectable. A high propensity for metastasis contributed
      to the poor outcome of patients with pelvic osteosarcoma. New therapeutic
      approaches are needed.

PMID- 15739211
TI  - Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but is one of the most
      aggressive human malignancies. Several prognostic factors have been observed in
      patients with ATC, and some experts advocate aggressive multimodal therapy in
      selected patients. However, it is unclear whether such an approach significantly
      improves survival. The authors analyzed prognostic factors and treatment outcomes
      in patients with ATC reported in the National Cancer Institute's Surveillance,
      Epidemiology, and End Results data base. METHODS: The cohort consisted of 516
      patients with ATC reported to 12 population-based cancer registries between 1973
      and 2000. Demographic, pathologic, and treatment data were used for univariate
      and multivariate survival analyses. RESULTS: The mean patient age at diagnosis
      was 71.3 years, and there were 171 men and 345 women. Eight percent of patients
      had intrathyroidal tumors, 38% had extrathyroidal tumors and/or lymph node
      invasion, and 43% of patients had distant metastasis. The average tumor size was
      6.4 cm (range, 1-15 cm). Sixty-four percent of patients underwent surgical
      resection of their primary tumor, and 63% received external beam radiotherapy.
      The overall cause-specific mortality rate was 68.4% at 6 months and 80.7% at 12
      months. Univariate analysis showed that age < 60 years, female gender,
      intrathyroidal tumor, external beam radiotherapy, surgical resection, and
      combined surgical resection of tumor and radiotherapy were associated with a
      lower cause-specific mortality. On multivariate analysis, only age < 60 years, an
      intrathyroidal tumor, and the combined use of surgical and external beam
      radiation therapy were identified as independent predictors of lower cause
      specific mortality. CONCLUSIONS: Although most patients with ATC had an extremely
      poor prognosis, patients < 60 years old with intrathyroidal tumors survived
      longer. Surgical resection with external beam radiotherapy for ATC was associated
      with lower cause-specific mortality.

PMID- 15739210
TI  - Randomized clinical trial of the effects of oral preoperative carbohydrates on
      postoperative nausea and vomiting after laparoscopic cholecystectomy.
AB  - BACKGROUND: A carbohydrate-rich drink (CHO) has been shown to reduce preoperative
      discomfort. It was hypothesized that it may also reduce postoperative nausea and
      vomiting (PONV). METHODS: Patients undergoing elective laparoscopic
      cholecystectomy under inhalational anaesthesia (127 women and 45 men; mean(s.d.)
      48(15) years) were randomized to either preoperative fasting, intake of CHO (50
      kcal/100 ml, 290 mOsm/kg) or placebo. The non-fasting groups were double-blinded;
      patients ingested 800 ml of liquid on the evening before surgery and 400 ml 2 h
      before anaesthesia. Nausea and pain scores on a visual analogue scale (VAS) and
      episodes of PONV were recorded up to 24 h after surgery. RESULTS: The incidence
      of PONV was lower in the CHO than in the fasted group between 12 and 24 h after
      surgery (P = 0.039). Nausea scores in the fasted and placebo groups were higher
      after operation than before admission to hospital (P = 0.018 and P < 0.001
      respectively), whereas there was no significant change in the CHO group. No
      intergroup differences in VAS scores were seen. The use of anaesthetics, opioids,
      antiemetics and intravenous fluids was similar in all groups. CONCLUSION: CHO may
      have a beneficial effect on PONV 12-24 h after laparoscopic cholecystectomy.

PMID- 15739212
TI  - Predicting complete removal of impalpable breast carcinomas using stereotactic
      radiologically guided surgery.

PMID- 15739213
TI  - Ultrafast dynamics of a solution in spatially restricted environments studied by
      photothermal spectroscopies.
AB  - The ultrafast dynamics of a solution in spatially restricted environments was
      studied by using the ultrafast transient lens (UTL) method. The UTL method is
      used to monitor the molecular dynamics of a solution by means of a change in the
      refractive index, which is advantageous for investigating the molecular dynamics
      of restricted systems. We investigated the photoisomerization of azobenzene
      derivatives in cyclodextrin nanocavities and revealed how the confinement affects
      the photoisomerization dynamics and yields. We also studied the relaxation
      dynamics of photo-excited auramine O (AuO) in a water/aerosol-OT/n-heptane
      reversed micelle. Both the perturbed properties of the included water and the
      interactions between AuO and the interface of the reversed micelle strongly
      appeared to affect the relaxation dynamics. At the same time, we observed a
      change in the refractive index suggesting a structural change of the micelles in
      the picosecond region that could not be detected by transient absorption
      spectroscopy. In addition, we developed the total internal reflection UTL (TIR
      UTL) method to monitor the ultrafast molecular dynamics at the liquid interface.
      The relaxation dynamics of photoexcited AuO at the silica/water interface were
      observed with subpicosecond time resolution, and it was revealed that the
      interaction with the interface strongly inhibited the relaxation process. These
      results demonstrated the advantages of the UTL method for investigating the
      molecular dynamics of a solution in spatially restricted environments.

PMID- 15739214
TI  - Randomized clinical trial comparing oral nifedipine with lateral anal
      sphincterotomy and tailored sphincterotomy in the treatment of chronic anal
      fissure.
AB  - BACKGROUND: The conventional treatment of chronic anal fissure is lateral
      sphincterotomy (LAS). The alternative options of tailored sphincterotomy (TS) and
      'chemical sphincterotomy' using medication such as nifedipine have recently
      become available. METHODS: A prospective randomized trial was conducted to
      compare LAS with TS and oral nifedipine. The main endpoints were fissure healing,
      symptom relief, recurrence and continence. RESULTS: One hundred and thirty-two
      patients were treated and followed up for 4 months. LAS was significantly more
      effective than TS in providing pain relief (P = 0.004) and better patient
      satisfaction (P = 0.020) at 4 weeks. Surgery (LAS and TS) was associated with
      significantly better fissure healing rates (both P < 0.001 at 16 weeks) and less
      recurrence (both P = 0.003) than nifedipine. There were substantial problems with
      compliance in the nifedipine group (17 of 41 patients), related to side-effects
      and slow healing. There were no differences in continence between the three
      treatment groups. CONCLUSION: LAS was most effective in providing pain relief and
      allowing rapid fissure healing, with minimal recurrence and no increased risk of
      incontinence, in patients with good anal sphincter function.

PMID- 15739215
TI  - Patterns of local disease failure and outcome after salvage surgery in patients
      with anal cancer.
AB  - BACKGROUND: Salvage surgery for anal cancer is usually reserved for local disease
      failure, but issues relating to the prediction of local failure and surgical
      outcome are ill defined. METHODS: Between 1988 and 2000, 254 patients with non
      metastatic anal epidermoid carcinoma were treated at a regional cancer centre
      with radiotherapy (n = 127) or chemoradiotherapy (n = 127). RESULTS: There were
      99 local disease failures (39.0 per cent), all but five occurring within 3 years
      of initial treatment. Increasing age (P < 0.001, Cox model), total radiation dose
      (P = 0.004) and tumour stage (P = 0.010) were independent predictors of local
      failure. The overall 3- and 5-year survival rates after local disease failure
      were 46 and 29 per cent; the corresponding rates after salvage surgery (73
      patients) were 55 and 40 per cent. A positive resection margin was the strongest
      negative predictor of survival after salvage surgery (P = 0.008, log rank test).
      Of 52 patients treated before the routine consideration of primary plastic
      reconstruction, delayed perineal wound healing occurred in 22 (42 per cent).
      CONCLUSION: In the management of anal cancer, local disease failure is a major
      clinical problem requiring early detection followed by radical surgery, often
      accompanied by plastic reconstruction. By implication, these factors favour the
      centralization of treatment for this uncommon cancer to a multidisciplinary
      oncology team.

PMID- 15739218
TI  - Diagnosis and management of pergolide-induced fibrosis.

PMID- 15739219
TI  - Ciprofloxacin-induced chorea.

PMID- 15739220
TI  - Foxn1 is required for tissue assembly and desmosomal cadherin expression in the
      hair shaft.
AB  - The mouse nude mutation inactivates the gene encoding the Foxn1 transcription
      factor, causing defective hair morphogenesis. Here, we show for the first time
      that Foxn1 is required for proper assembly of the hair medulla, and we identify
      Foxn1-regulated genes by transcript profiling. One such gene encodes the
      desmosomal cadherin, Dsc2. Significantly, Foxn1-dependent Dsc2 expression is
      restricted to the hair medulla, and within these cells, Dsc2 protein is
      predominantly localized to specialized adhesion junctions between the cortex and
      the medulla. Our results reveal Foxn1 as an essential regulator of tissue
      assembly in the growing hair shaft and implicate Dsc2 as a downstream effector of
      this activity.

PMID- 15739221
TI  - Genomic resources for chicken.
AB  - The recent sequencing and draft assembly of a chicken genome has provided
      biologists with an invaluable research tool that complements a growing list of
      additional avian genomic resources. For many researchers, finding and using these
      resources is challenging, because information is presented through an increasing
      number of Web sites and browser navigation frequently requires specific knowledge
      and expertise. This primer provides an overview of online genomic resources for
      the chicken, including the Ensembl, UCSC, and NCBI annotated chicken genome
      browsers; expressed sequence tag and in situ hybridization databases; and sources
      for microarrays, cDNAs, and bacterial artificial chromosomes (BACs). Several
      short tutorials oriented toward the biologist with limited bioinformatics skills
      outline how to retrieve several types of commonly needed information and
      reagents.

PMID- 15739222
TI  - JNK and ROKalpha function in the noncanonical Wnt/RhoA signaling pathway to
      regulate Xenopus convergent extension movements.
AB  - The Wnt/planar cell polarity (PCP) pathway plays a critical role in wing, eye,
      and sensory bristle development of Drosophila and in convergent extension (CE)
      movements during vertebrate gastrulation. In Drosophila, Jun N-terminal kinase
      (JNK) and Rho-associated kinase (ROK) participate in RhoA-mediated PCP pathway
      during eye and wing development. In mammalian cells, Rac1 and Cdc42 but not RhoA
      are required for JNK activation by Wnt/PCP signals. However, there has been no
      evidence that Rho GTPases regulate JNK activation in Wnt/PCP pathway during
      Xenopus CE movements. Here, we report that Xenopus RhoA (XRhoA), but not Xenopus
      Cdc42 (XCdc42), is essential for JNK activation downstream of the Wnt/PCP pathway
      during Xenopus CE movements, and the phenotypic effect of loss of XRhoA function
      was rescued by Xenopus JNK1 (XeJNK1). In addition, XRhoA rescues the inhibition
      of CE movements by the DEP domain deletion mutant of Xenopus Dsh (Xdsh-DeltaDEP),
      which has dominant negative (DN) effects on JNK activation, and the PDZ domain
      deletion mutant of Xdsh (Xdsh-DeltaPDZ). Moreover, we demonstrate that Xenopus
      Rho-associated kinase alpha (xROKalpha), which is expressed mainly in mesoderm
      and ectoderm that undergo extensive cell rearrangements, regulates CE movements
      without affecting gene expression, and injection of xROKalpha rescued the
      inhibition of CE movements caused by DN XRhoA. Finally, we show that ROKalpha and
      JNK synergistically rescued embryos overexpressing DN XRhoA, which exhibit
      gastrulation defects, although ROKalpha is not required for JNK activation.
      Together, these data suggest that JNK and ROKalpha function in the noncanonical
      Wnt/RhoA pathway to regulate Xenopus CE movements.

PMID- 15739224
TI  - Segregation of arterial and venous markers in subpopulations of blood islands
      before vessel formation.
AB  - The neuropilin-1 (np1) and the neuropilin-2 (np2) receptors bind vascular
      endothelial growth factor (VEGF) and class-3 semaphorins. They form complexes
      with VEGF tyrosine-kinase receptors or alternatively with type-A plexins to
      transduce respective VEGF or semaphorin signals. We have compared the expression
      patterns of np1, np2, plexin-A1, and plexin-A2 in the emerging vasculature of
      chick embryos. Double in situ hybridization reveals that six-somite embryos
      contain intermingled extraembryonic blood island (BI) subpopulations that express
      np1 or np2 as well as a BI subpopulation that coexpresses both neuropilins. In 13
      somite embryos, which already contain an extraembryonic vascular plexus, the
      expression of np1 and np2 is segregated between the arterial and venous parts of
      the plexus, despite the absence of blood flow. However, the arterial marker
      ephrin-B2 was not yet expressed in the plexus at this stage. In 26-somite
      embryos, which possess a functional vascular system, np1 and np2 are
      differentially expressed in arteries and veins as previously reported. At this
      stage, posterior BIs expressing np2 appear to undergo fusion to form the
      posterior sinus vein and its tributaries, suggesting that the venous identity of
      these veins may be established before their formation. The neuropilin coreceptor
      plexin-A2 was expressed in extraembryonic veins but not in extraembryonic
      arteries. In contrast, within the embryo, plexin-A2 expression was observed in
      the dorsal aorta as well as in the cardinal vein. Semaphorin-3F (s3f), an np2
      ligand, bound to np2-expressing cells in 26-somite embryos regardless of the
      presence or absence of plexin-A1 or plexin-A2. Of interest, even though s3f binds
      to np1 in vitro, np1-expressing arteries fail to bind s3f in whole-mount binding
      experiments.

PMID- 15739223
TI  - her9 promotes floor plate development in zebrafish.
AB  - Notochord, floor plate, and in anamniotes hypochord, are vertebrate embryonic
      midline structures that are the sources of molecules that pattern the nervous
      system, somites, and dorsal aorta. Midline precursor cells arise from the dorsal
      organizer during gastrulation, and Notch signaling is an important regulator of
      midline cell fate specification. To understand fully how Notch signaling
      regulates midline development, we investigated the role of potential Notch target
      genes. We show here that midline precursors express her9, a member of the
      hairy/Enhancer of split gene family. Although her9 inhibits notochord development
      and promotes floor plate specification, her9 expression in floor plate cells
      appears not to require Notch signaling. We show that, instead, her9 is a
      downstream effector of Nodal signaling for floor plate specification.

PMID- 15739225
TI  - Developmental expression of metalloproteases ADAM 9, 10, and 17 becomes
      restricted to divergent pancreatic compartments.
AB  - The A Disintegrin And Metalloprotease (ADAM) family of metalloproteases affects a
      variety of proteins with important roles in development and disease, including
      growth factors and adhesion molecules. We have analyzed the expression patterns
      of ADAMs 9, 10, and 17 during pancreas ontogeny. All ADAMs investigated were
      expressed in the pancreatic anlagen but invariably became restricted to divergent
      pancreatic compartments. ADAM9 and 17 became restricted to the insulin-producing
      beta-cells and all islet cells, respectively. During embryogenesis, ADAM10 was
      detected predominantly in acinar cells, but in the adult, it was localized to the
      cell surface membrane of both endocrine and exocrine cells. In addition to ADAM9,
      a potential prognostic factor for ductal cancers, we describe the expression of
      ADAM10 and ADAM17 in the pancreatic ductal epithelium. Altogether, the dynamic
      expression profile of the ADAM proteases described here may reflect a functional
      divergence of these as mediators of pancreas biology.

PMID- 15739226
TI  - Spatial variability in the mineralisation of the phenylurea herbicide linuron
      within a Danish agricultural field: multivariate correlation to simple soil
      parameters.
AB  - The spatial variability in the mineralisation rate of linuron [N-(3,4
      dichlorophenyl)-N'-methoxy-N'-methylurea] was studied within a previously treated
      Danish agricultural field by sampling soils from eleven different plots randomly
      distributed across an area of 20 x 20 m. The soils were characterised with
      respect to different abiotic and biotic properties including moisture content,
      organic matter content, pH, nutrient content, bacterial biomass, potential for
      mineralisation of MCPA [(4-chloro-2-methylphenoxy)acetic acid] and linuron. Five
      soils had a potential for mineralisation of linuron, with 5-15% of the added
      [ring-U-14C]linuron metabolised to 14CO2 within 60 days at 10 degrees C, while no
      extensive mineralisation of linuron was observed in the six remaining soils
      within this period. A TLC analysis of the methanol-extractable residues showed no
      development of 14C-labelled metabolites from linuron in any of the samples.
      Multivariate analysis was conducted to elucidate relationships between the
      intrinsic properties of single soil samples and initial rate of linuron
      mineralisation. The analysis indicated that important soil parameters in
      determining the spatial heterogeneity included the C(total)/N(total) ratio, pH
      and the water-extractable potassium contents, with the first of these highly
      negatively correlated and the last two highly positively correlated to the
      initial linuron mineralisation rate. This study shows that enhanced
      biodegradation of linuron may develop with successive field treatments, but that
      considerable in-field spatial heterogeneity in the degradation rate still exists.
      Combined with a parallel enrichment study focused on the underlying microbial
      processes, the present results suggest that intrinsic soil properties affect the
      linuron-metabolising bacterial population and thereby determine the spatial
      variability in the linuron mineralisation activity.

PMID- 15739227
TI  - Retinoic acid generated by Raldh2 in mesoderm is required for mouse dorsal
      endodermal pancreas development.
AB  - Studies on nonmammalian vertebrate embryos have indicated that retinoic acid (RA)
      is required for pancreas development. We have analyzed mouse embryos carrying a
      null mutation of the gene encoding retinaldehyde dehydrogenase 2 (Raldh2), which
      controls RA synthesis. Raldh2-/- embryos specifically lack expression of Pdx1 (a
      homeobox gene required for pancreas development) and Prox1 in dorsal endodermal
      but not ventral endodermal pancreatic precursor tissues. Ventral endodermal
      expression of Hex is not affected in Raldh2-/- embryos, indicating that liver
      specification is not dependent upon RA. Also, expression of Foxa2 across the
      dorsoventral axis of the endoderm is not affected in Raldh2-/- embryos,
      indicating that a lack of RA does not cause a general defect in foregut endoderm
      development. Comparison of wild-type and Raldh2-/- embryos carrying an RA
      reporter transgene demonstrates that RA activity is normally present throughout
      the endoderm except in the ventral-most region but is totally missing in endoderm
      of Raldh2-/- embryos. Thus, Raldh2 expressed in adjacent splanchnic lateral plate
      mesoderm provides an RA signal to dorsal endoderm. Dorsal Pdx1 expression is
      rescued in Raldh2-/- embryos by low-dose maternal administration of RA, which
      preferentially restores RA-reporter expression in the dorsal endoderm. Our
      findings demonstrate a specific role for RA in mouse embryos as a mesodermally
      synthesized signal needed for dorsal endodermal expression of Pdx1 during
      development of the dorsal pancreatic lineage.

PMID- 15739228
TI  - Fibrous component of the blastocoelic extracellular matrix shapes epithelia in
      concert with mesenchyme cells in starfish embryos.
AB  - By using a monoclonal antibody (4H11 Mab), we have investigated morphogenetic
      functions of a fibrous component of the blastocoelic extracellular matrix in
      relation to cellular activities during early development of the starfish Asterina
      pectinifera. The 4H11 fibers fill the blastocoele from the late-cleavage to late
      gastrula stage and contain the 370-kDa proteinaceous molecule secreted only by
      the epithelial cells. When 4H11 Mab is introduced into the blastocoele of
      blastulae, the embryos reveal three distinct morphological abnormalities after
      the mid-gastrula stage: (1) Distribution of mesenchyme cells confined near the
      tip of the archenteron, (2) swelling of the posterior ectoderm, and (3)
      suppressed growth of the mouth, esophagus, and coelomic pouches. These
      abnormalities occur together with alterations in the distribution of the 4H11
      fibers. In embryos recovering from the effect of 4H11 Mab, the mesenchyme cells
      rearrange the 4H11 fibers. We propose that 4H11 fibers play direct roles in the
      morphogenesis of starfish embryos by providing a dynamic scaffold not only for
      the mesenchyme cells but also for the epithelial cells. Moreover, 4H11 fibers
      have a resist force from within, in concert with the mesenchyme cells, to counter
      the bulging force intrinsic to the epithelia and hold the epithelia in specific
      positions, once the positions have been decided.

PMID- 15739229
TI  - Membrane-type 1 matrix metalloproteinase is required for normal alveolar
      development.
AB  - Matrix metalloproteinases (MMPs) are expressed during lung development, but their
      role may be limited, as mice deficient in MMP-3, 7, 9, or 12 develop a normal
      adult lung. Because membrane-type 1 matrix metalloproteinase (MT1-MMP) is
      expressed in the developing lung epithelium, we examined the lung structure of
      MT1-MMP-deficient (-/-) mice. Branching morphogenesis was normal, but alveolar
      development was abnormal in the MT1-MMP-/- lungs with 40% less alveolar surface
      area at 1 month (P < 0.01). MT1-MMP-/- airways and alveoli had an abnormal
      ultrastructural appearance, but epithelial cell differentiation markers were
      distributed similarly in both strains. There was no evidence of excess
      extracellular matrix deposition or inflammation at the time points examined. In
      contrast, by adulthood MMP-2-/- mice had normal alveolar size and structure,
      indicating normal alveolar development was not dependent on the ability of MT1
      MMP to activate pro-MMP-2. These data indicate that MT1-MMP is required for
      normal lung development.

PMID- 15739230
TI  - DNA methyltransferase expression in the mouse germ line during periods of de novo
      methylation.
AB  - DNA methyltransferase (DNMT) 3A and DNMT3B are both active de novo DNA
      methyltransferases required for development, whereas DNMT3L, which has no
      demonstrable methyltransferase activity, is required for methylation of imprinted
      genes in the oocyte. We show here that different mechanisms are used to restrict
      access by these proteins to their targets during germ cell development.
      Transcriptional control of the Dnmt3l promoter guarantees that message is low or
      absent except during periods of de novo activity. Use of an alternative promoter
      at the Dnmt3a locus produces the shorter Dnmt3a2 transcript in the germ line and
      postimplantation embryo only, whereas alternative splicing of the Dnmt3b
      transcript ensures that Dnmt3b1 is absent in the male prospermatogonia. Control
      of subcellular protein localization is a common theme for DNMT3A and DNMT3B, as
      proteins were seen in the nucleus only when methylation was occurring. These
      mechanisms converge to ensure that the only time that functional products from
      each locus are present in the germ cell nuclei is around embryonic day 17.5 in
      males and after birth in the growing oocytes in females.

PMID- 15739231
TI  - Genomic, cDNA, and embryonic expression analysis of zebrafish transforming growth
      factor beta 3 (tgfbeta3).
AB  - TGFbeta3, a member of the transforming growth factor beta family, regulates a
      spectrum of biological processes and is involved in mammalian pulmonary and
      craniofacial development. Homologs of human TGFbeta3 have been identified in
      several vertebrate species. We sequenced a cDNA clone of zebrafish tgfbeta3,
      consisting of a 271-bp 5' untranslated region, a 1,233-bp open reading frame that
      encodes a predicted 410 amino acid peptide, and a 527-bp 3' untranslated region.
      Using 5' rapid amplification of cDNA ends, the transcription start site of this
      gene was determined to lie an additional 29 nucleotides upstream. The gene is
      composed of seven exons and maps to a segment of linkage group 17 that is
      syntenic to the human TGFbeta3 locus on chromosome 14q24. One stimulating protein
      1 (Sp1) and two (TATA binding protein) (TBP) transcription factor binding sites
      were identified in the putative promoter segment upstream of the transcription
      start site. Comparative alignment analysis revealed a high degree of tgfbeta3
      nucleotide and amino acid identity between zebrafish and other species, including
      complete conservation of the cysteine knot structure that facilitates protein
      protein interaction. Also, 9 of 10 amino acid residues critical for
      ligand/receptor binding in human TGFbeta3 are conserved in zebrafish, suggesting
      a high degree of functional conservation even in lower vertebrates. Zebrafish
      tgfbeta3 transcripts were first detected in the notochord (10 somite to high-pec
      stage), followed by expression in the developing pharyngeal arch and neurocranial
      cartilage (18 somite to protruding mouth stage), lens and heart (21 somite to
      protruding mouth stage), and pectoral fins (prim-25 to protruding mouth stage).
      The strong expression in the pectoral fins, not reported in the orthologous
      mammalian forelimb, suggests a modified or novel function of tgfbeta3 during
      early fish development.

PMID- 15739232
TI  - Immunocytochemical mapping and quantification of expression of a putative type 1
      serotonin receptor in the crayfish nervous system.
AB  - Serotonin is an important neurotransmitter that is involved in modulation of
      sensory, motor, and higher functions in many species. In the crayfish, which has
      been developed as a model for nervous system function for over a century,
      serotonin modulates several identified circuits. Although the cellular and
      circuit effects of serotonin have been extensively studied, little is known about
      the receptors that mediate these signals. Physiological data indicate that
      identified crustacean cells and circuits are modulated via several different
      serotonin receptors. We describe the detailed immunocytochemical localization of
      the crustacean type 1 serotonin receptor, 5-HT1crust, throughout the crayfish
      nerve cord and on abdominal superficial flexor muscles. 5-HT1crust is widely
      distributed in somata, including those of several identified neurons, and
      neuropil, suggesting both synaptic and neurohormonal roles. Individual animals
      show very different levels of 5-HT1crust immunoreactivity (5-HT(1crust)ir)
      ranging from preparations with hundreds of labeled cells per ganglion to some
      containing only a handful of 5-HT(1crust)ir cells in the entire nerve cord. The
      interanimal variability in 5-HT(1crust)ir is great, but individual nerve cords
      show a consistent level of labeling between ganglia. Quantitative RT-PCR shows
      that 5-HT1crust mRNA levels between animals are also variable but do not directly
      correlate with 5-HT(1crust)ir levels. Although there is no correlation of 5
      HT1crust expression with gender, social status, molting or feeding, dominant
      animals show significantly greater variability than subordinates. Functional
      analysis of 5-HT1crust in combination with this immunocytochemical map will aid
      further understanding of this receptor's role in the actions of serotonin on
      identified circuits and cells.

PMID- 15739233
TI  - Integrin repertoire on myogenic cells changes during the course of primary
      myogenesis in the mouse.
AB  - Cells interact with the extracellular matrix through receptors, most commonly of
      the integrin family. We (Cachaco et al. [2003] Development 130:1659-1671) and
      others (Schwander et al. [2003] Dev. Cell 4:673-685) have demonstrated a role for
      beta1 integrins in mouse primary myogenesis. However, it is unclear what alpha
      subunits pair with beta1 during this process in vivo. Here, we determined alpha
      subunit expression patterns at embryonic day (E) 11.5-E14.5. Differentiated
      myotomal myocytes express all alpha subunits studied. As the muscle masses form
      both in trunk (E12.5) and limbs (E11.5-E12.5), laminin receptors alpha6beta1 and
      alpha7beta1 are undetectable, and an assembled laminin matrix is absent. Instead
      alpha1beta1, alpha4beta1, alpha5beta1, and an alpha v-containing integrin are
      expressed and unassembled laminin and fibronectin are abundant around myogenic
      cells. At E13.5-E14.5, alpha6beta1 and alpha7beta1 are expressed, and a laminin
      matrix forms around individual myotubes. Thus, myogenic cells change their
      integrin expression pattern during the course of primary myogenesis in the mouse,
      suggesting different roles for fibronectin- and laminin-containing matrices in
      this process.

PMID- 15739234
TI  - Molecular characterization and biological response to respiration inhibitors of
      Pyricularia isolates from ctenanthe and rice plants.
AB  - The molecular profile and the biological response of isolates of Pyricularia
      oryzae Cavara obtained from ctenanthe to two strobilurins (azoxystrobin, kresoxim
      methyl) and the phenylpyridinamine fungicide fluazinam were characterized, and
      compared with isolates from rice plants. Five different isozymes (alpha-esterase,
      lactate, malate, isocitrate and sorbitol dehydrogenases) and five random decamer
      primers for RAPD-PCR were used to generate molecular markers. Using unweighted
      pair-group with arithmetic average analysis, ctenanthe isolates were found to
      form a separate group distinct from that of the rice isolates for both sets of
      markers. Amplified polymorphic sequences of mitochondrial cytochrome b that were
      digested with Fnu4HI or StyI revealed no differences among Pyricularia isolates
      at amino acid positions 143 or 129 which confer resistance to strobilurins in
      several fungi. In absence of the alternative respiration inhibitor
      salicylhydroxamic acid (SHAM) the three fungicides showed inferior and variable
      efficacy, with a trend toward the rice isolate being less sensitive. The addition
      of SHAM enhanced the effectiveness of all fungicides against isolates regardless
      of their origin. Appressorium formation was the most vulnerable target of action
      of the respiration inhibitors and azoxystrobin the most effective. This is the
      first report of a comparison between the molecular profiles and sensitivities to
      respiration inhibitors for Pyricularia oryzae isolates from a non-gramineous host
      and from rice.

PMID- 15739235
TI  - Development of cholinergic amacrine cells is visual activity-dependent in the
      postnatal mouse retina.
AB  - In the present study, we used immunocytochemistry to study the temporal and
      spatial arrangement of mouse cholinergic amacrine cells during postnatal retinal
      development under normal light/dark cycles and during visual deprivation. Choline
      acetyltransferase (ChAT)-immunolabeled cells were detected in the neuroblastic
      layer (NBL) and in the ganglion cell layer (GCL) at postnatal day 0 (P0). Between
      P3-5, two characteristic cholinergic bands were clearly identified in the inner
      plexiform layer (IPL). The signal intensity of somas and processes progressively
      increased over the first 2 postnatal weeks. Around eye opening at P12,
      cholinergic neurons were mature-like. This early developmental process was not
      altered by visual deprivation. After eye opening, the space between the two
      cholinergic bands increased continuously and the spatial regularity index changed
      constantly, indicating that the cholinergic neurons possibly underwent refinement
      during later postnatal development. The changes occurring following eye opening
      were retarded by visual deprivation. The morphologies of photoreceptors,
      horizontal cells, recoverin-positive OFF-cone bipolar cells, rod bipolar cells,
      dopaminergic amacrine cells, and Muller cells appeared normal. Their
      stratification in the outer plexiform layer (OPL) and the IPL was not affected by
      visual deprivation. However, glial cells grew vertically across the entire
      thickness of dark-reared retinas. Our results suggest that the development of
      cholinergic neurons before eye opening is independent of the lighting conditions.
      Their development after eye opening is greatly impeded by visual deprivation.
      This visual activity-dependent phase of development may be a critical period for
      the maturation and synaptic wiring of cholinergic amacrine cells in the mammalian
      retina.

PMID- 15739236
TI  - Differential regulation of GABA(A) receptor and gephyrin postsynaptic clustering
      in immature hippocampal neuronal cultures.
AB  - Gephyrin is a postsynaptic scaffolding protein involved in clustering of glycine-
      and GABA(A) receptors at inhibitory synapses. The role of gephyrin in GABAergic
      synapses, the nature of its interactions with GABA(A) receptors, and the
      mechanisms of targeting to GABAergic synapses are largely unknown. To gain
      further insights into these questions, the formation of GABA(A) receptor and
      gephyrin clusters and their distribution relative to presynaptic terminals were
      investigated in immature cultures of embryonic hippocampal neurons using triple
      immunofluorescence staining. GABA(A) receptor clusters, labeled for the alpha2
      subunit, formed independently of gephyrin clusters, and were distributed on
      neurites at constant densities, either extrasynaptically or, to a lesser extent,
      postsynaptically, apposed to synapsin-I-positive axon terminals. In contrast,
      gephyrin clusters were always associated with GABA(A) receptors and were
      preferentially localized postsynaptically. Their density increased linearly with
      the extent of innervation, which developed rapidly during the first week in
      vitro. These results suggested that GABA(A) receptor clustering is mediated by
      cell-autonomous mechanisms independent of synapse formation. Their association
      with gephyrin is dynamically regulated and may contribute to stabilization at
      postsynaptic sites. Labeling for vesicular glutamate transporters revealed that
      most synapses in these immature cultures were presumably glutamatergic, implying
      that postsynaptic GABA(A) receptor and gephyrin clusters initially were located
      in "mismatched" synapses. However, clusters appropriately localized in GABAergic
      synapses were distinctly larger and more intensely stained. Altogether, these
      results demonstrate that the targeting of GABA(A) receptor and gephyrin clusters
      to GABAergic synapses occurs secondarily and is regulated by presynaptic factors
      that are not essential for clustering.

PMID- 15739237
TI  - Organization of tectopontine terminals within the pontine nuclei of the rat and
      their spatial relationship to terminals from the visual and somatosensory cortex.
AB  - We investigated the spatial relationship of axonal and dendritic structures in
      the rat pontine nuclei (PN), which transfer visual signals from the superior
      colliculus (SC) and visual cortex (A17) to the cerebellum. Double anterograde
      tracing (DiI and DiAsp) from different sites in the SC showed that the tectal
      retinotopy of visual signals is largely lost in the PN. Whereas axon terminals
      from lateral sites in the SC were confined to a single terminal field close to
      the cerebral peduncle, medial sites in the SC projected to an additional
      dorsolateral one. On the other hand, axon terminals originating from the two
      structures occupy close but, nevertheless, totally nonoverlapping terminal fields
      within the PN. Furthermore, a quantitative analysis of the dendritic trees of
      intracellularly filled identified pontine projection neurons showed that the
      dendritic fields were confined to either the SC or the A17 terminal fields and
      never extended into both. We also investigated the projections carrying cortical
      somatosensory inputs to the PN as these signals are known to converge with tectal
      ones in the cerebellum. However, terminals originating in the whisker
      representation of the primary somatosensory cortex and in the SC were located in
      segregated pontine compartments as well. Our results, therefore, point to a
      possible pontocerebellar mapping rule: Functionally related signals, commonly
      destined for common cerebellar target zones but residing in different afferent
      locations, may be kept segregated on the level of the PN and converge only later
      at specific sites in the granular layer of cerebellar cortex.

PMID- 15739238
TI  - Pore-forming subunits of K-ATP channels, Kir6.1 and Kir6.2, display prominent
      differences in regional and cellular distribution in the rat brain.
AB  - K-ATP channels consist of two structurally different subunits: a pore-forming
      subunit of the Kir6.0-family (Kir6.1 or Kir6.2) and a sulfonylurea receptor
      (SUR1, SUR2, SUR2A, SUR2B) with regulatory activity. The functional diversity of
      K-ATP channels in brain is broad and of fundamental importance for neuronal
      activity. Here, using immunocytochemistry with monospecific antibodies against
      the Kir6.1 and Kir6.2 subunits, we analyze the regional and cellular distribution
      of both proteins in the adult rat brain. We find Kir6.2 to be widely expressed in
      all brain regions, suggesting that the Kir6.2 subunit forms the pore of the K-ATP
      channels in most neurons, presumably protecting the cells during cellular stress
      conditions such as hypoglycemia or ischemia. Especially in hypothalamic nuclei,
      in particular the ventromedial and arcuate nucleus, neurons display Kir6.2
      immunoreactivity only, suggesting that Kir6.2 is the pore-forming subunit of the
      K-ATP channels in the glucose-responsive neurons of the hypothalamus. In
      contrast, Kir6.1-like immunolabeling is restricted to astrocytes (Thomzig et al.
      [2001] Mol Cell Neurosci 18:671-690) in most areas of the rat brain and very weak
      or absent in neurons. Only in distinct nuclei or neuronal subpopulations is a
      moderate or even strong Kir6.1 staining detected. The biological functions of
      these K-ATP channels still need to be elucidated.

PMID- 15739239
TI  - Axial coordination of carboxylate activates the non-heme FeIV=O unit.

PMID- 15739241
TI  - Large-scale synthesis of silver nanocubes: the role of HCl in promoting cube
      perfection and monodispersity.

PMID- 15739240
TI  - Neurochemical organization of chimpanzee inferior pulvinar complex.
AB  - The pulvinar of primates, which connects with all visual areas, has been
      implicated in visual attention and in control of eye movements. Recently, five
      separate neurochemical subdivisions of a region termed the inferior pulvinar
      complex have been identified in monkeys (Gray et al. [1999] J Comp Neurol 409:452
      468; Gutierrez et al. [1995] J Comp Neurol 363:545-562), and comparable
      subdivisions have been mapped in humans (Cola et al. [1999] NeuroReport 10:3733
      3738). In the present study, we investigated the inferior pulvinar of the
      chimpanzee (Pan troglodytes), the closest evolutionary relative of humans, using
      cytochrome oxidase (CO) and acetylcholinesterase (AChE) histochemistry, and
      immunocytochemistry for calbindin. Each staining method demarcated five
      histochemical zones corresponding, from medial to lateral, to the posterior
      (PI(P)), medial (PI(M)), central PI(C)), lateral (PI(L)), and the lateral-shell
      (PI(L-S)) divisions in monkeys. The PI(P) division stained darkly for calbindin
      and lightly for CO and AChE. The PI(M) division was characterized by less
      neuropil staining for calbindin, and by distinct, intensely stained patches of CO
      and AChE. PI(C) appeared lighter than adjacent divisions with CO and AChE
      histochemistry and was moderately stained with calbindin. PI(L) was moderately to
      darkly stained with each method and was adjoined by a lighter staining shell,
      PI(L-S). Thus, in the aspects of organization we examined, the inferior pulvinar
      of chimpanzees closely resembles that of humans and monkeys. This investigation
      provides a foundation for more detailed studies of the thalamic relationships of
      extrastriate cortex in apes and humans.

PMID- 15739242
TI  - Template-dependent morphogenesis of oriented calcite crystals in the presence of
      magnesium ions.

PMID- 15739243
TI  - Analysis of N7-(benzo[a]pyrene-6-yl)guanine in urine using two-step solid-phase
      extraction and isotope dilution with liquid chromatography/tandem mass
      spectrometry.
AB  - Analysis of urinary N7-(benzo[a]pyren-6-yl)guanine (BP-6-N7Gua), a DNA adduct
      induced by benzo[a]pyrene, may serve as a risk-associated biomarker for exposure
      to polyaromatic hydrocarbons (PAHs). In this study a highly sensitive and
      specific analytical method, incorporating on-line sample preparation coupled with
      isotope-dilution liquid chromatography and tandem mass spectrometry (LC/MS/MS),
      was developed to quantitate this adduct in human urine. In order to achieve
      accurate quantitation, 15N5-labeled BP-6-N7Gua was synthesized to serve as the
      internal standard, and a two-step solid-phase extraction (SPE) procedure using C8
      and SCX cartridges was used for sample cleanup. BP-6-7-N7Gua was analyzed using
      positive ion LC/MS/MS operated in multiple reaction monitoring (MRM) mode. The
      [M+H]+ ions at m/z 402 and 407 and the common fragment ion of [M+H]+ at m/z 252
      were monitored for quantification. The recovery of this analyte after two-step
      SPE was 90%, and the limit of detection was 2.5 fmol/mL in 10 mL of urine. This
      highly specific and sensitive method for BP-6-N7Gua in urine may be applied to
      assess exposure to PAHs in coke-oven workers for future molecular epidemiology
      studies on health effects of PAHs.

PMID- 15739244
TI  - A new maleimide-bound acid-cleavable solid-support reagent for profiling
      phosphorylation.
AB  - A new chemical strategy for phosphopeptide profiling is reported in this study.
      Phosphorylation represents one of the most important classes of posttranslational
      modifications of proteins. Here we report a generalized strategy that employs
      solid-phase capture and mass-encoding steps to selectively enrich phosphopeptides
      from complex mixtures. This method exploits conversion of phosphates into thiols
      and reactive compounds to selectively isolate products of phosphorylation.
      Selective isolation of phosphopeptides is achieved with a simple, novel, acid
      cleavable, solid-support-bound maleimide reagent. Our chemistry efforts have
      focused on minimization of linker size and simplification of reagent production
      with incorporation of common solid-phase peptide synthesis steps. Relative
      quantitation was demonstrated by modifying phosphopeptides with incorporation of
      ethanedithiol and propanedithiol. We observed that appropriate normalization is
      necessary to utilize mass tag strategies for relative quantitation of
      posttranslational modifications. The utility of solid-phase capture was
      determined with model phosphopeptides, and the method was demonstrated with
      enriching phosphopeptides from beta-casein, alpha-casein and ovalbumin. The solid
      phase capture and release methods were also demonstrated with unfractionated
      whole histone protein mixtures to show this compound applicability in real
      biological samples. The new chemical strategy will ultimately be utilized for
      high-throughput profiling of phosphorylation and possibly other posttranslational
      modifications.

PMID- 15739245
TI  - Incidence of deep vein thrombosis after varicose vein surgery (Br J Surg 2004;
      91: 1582-1585).

PMID- 15739247
TI  - Living donor liver transplantation.

PMID- 15739248
TI  - Effects of a selective cyclo-oxygenase 2 inhibitor on colonic anastomotic and
      skin wound integrity (Br J Surg 2004; 91: 1613-1618).

PMID- 15739249
TI  - Treatment of peritoneal dissemination from gastric cancer by peritonectomy and
      chemohyperthermic peritoneal perfusion.
AB  - BACKGROUND: There is no standard treatment for peritoneal dissemination from
      gastric cancer. A novel treatment consisting of peritonectomy and intraoperative
      chemohyperthermic peritoneal perfusion (CHPP) was compared with conventional
      surgery and CHPP. METHODS: Records of all patients who underwent CHPP after
      cytoreductive surgery between 1992 and 2002 were reviewed. RESULTS: Data for 107
      patients with peritoneal dissemination were available. Complete cytoreduction was
      achieved in 47 (43.9 per cent) of the 107 patients: 18 of 65 who underwent
      conventional surgery and 29 of 42 who had peritonectomy. Twenty-three patients
      (21.5 per cent) suffered from complications. The overall operative mortality rate
      was 2.8 per cent. Seventeen patients (15.9 per cent) were disease free and 87
      subsequent deaths were related to disease progression. The median survival for
      all patients was 11.5 months, with a 5-year survival rate of 6.7 per cent. Median
      survival after complete cytoreduction was 15.5 months and that after incomplete
      cytoreduction was 7.9 months, with 5-year survival rates of 13 and 2 per cent
      respectively. Completeness of cytoreduction and peritonectomy were independent
      prognostic factors. The 5-year survival rate after complete cytoreduction by
      peritonectomy with CHPP was 27 per cent. CONCLUSION: Complete cytoreduction after
      peritonectomy and CHPP may improve the survival of patients with peritoneal
      dissemination from gastric cancer.

PMID- 15739250
TI  - Radioimmunotherapy and colorectal cancer.
AB  - BACKGROUND: Despite the success of radioimmunotherapy (RIT) using radiolabelled
      monoclonal antibodies (Mabs) directed against tumour-associated antigens in the
      treatment of non-Hodgkin's lymphoma, therapeutic success in solid tumours has
      been modest. In the past decade, a dozen Mabs have been investigated clinically
      for their potential usefulness in RIT of colorectal cancer. METHODS: The
      application of radiolabelled Mabs for the treatment of solid cancers is
      discussed, and clinical trials investigating RIT for colorectal cancer listed in
      the Medline and Embase databases are reviewed. RESULTS: Uptake of radiolabelled
      Mabs in tumour and, consequently, the therapeutic efficacy of RIT is inversely
      correlated with tumour size. The bone marrow is the most important dose-limiting
      organ. Twenty-three phase I/II studies were found that investigated the
      feasibility and efficacy of RIT using five radionuclides and 15 Mabs against
      carcinoembryonic antigen, tumour-associated glycoprotein 72, epithelial cellular
      adhesion molecule, A33 or colon-specific antigen p, mainly in patients with
      advanced colorectal cancer. A few responses were recorded but no particular
      antibody construct seemed superior. CONCLUSION: RIT might be an effective
      adjuvant treatment modality in colorectal cancer. Future studies should focus on
      its application in patients with small-volume or minimal residual disease.

PMID- 15739251
TI  - Using information technology to improve surgical safety (Br J Surg 2004; 91: 939
      940).

PMID- 15739252
TI  - Systematic review of sacral nerve stimulation for faecal incontinence and
      constipation (Br J Surg 2004; 91: 1559-1569).

PMID- 15739253
TI  - New anticoagulants and thromboprophylaxis.

PMID- 15739254
TI  - Randomized clinical trial of the effect of pneumoperitoneum on cardiac function
      and haemodynamics during laparoscopic cholecystectomy (Br J Surg 2004; 91: 848
      854).

PMID- 15739255
TI  - Fibrinogen and fragment D-induced vascular constriction.
AB  - Elevated fibrinogen (Fg) concentration in blood is a high risk factor for many
      cardiovascular diseases. We hypothesize that Fg and its early degradation
      product, fragment D, may result in arterial constriction by binding endothelial
      intercellular adhesion molecule-1 (ICAM-1). The vasoconstriction induced by Fg
      and fragment D was studied in third- and second-order arterioles (3As and 2As,
      respectively) of Sprague-Dawley rat cremaster muscle in vivo, in aortic and
      femoral artery rings, and in the segments of first-order arterioles (1As)
      isolated from rat cremaster muscle. Intravascular infusion of Fg induced
      significant constriction of 3As and 2As (by 33.4 +/- 3.4 and 23.7 +/- 4.3%,
      respectively) in vivo and was abolished in the presence of the specific
      endothelin type A receptor blocker BQ-610. Fg and fragment D produced significant
      constriction of both aortic and femoral artery rings. Isolated 1As constricted in
      response to Fg (0.3 microM) and fragment D (3 microM) by 31 +/- 1.4 and 12 +/-
      1.5%, respectively. Fluorescently labeled Fg and fragment D bound to the vascular
      wall, whereas albumin bound to a significantly lesser degree. The binding of Fg
      and fragment D to the arteriolar wall and constriction of aortic and femoral
      artery rings as well as isolated 1As were abolished in the presence of anti-Fg
      and anti-ICAM-1 antibodies. These results indicate that binding of Fg and
      fragment D to the vascular wall through ICAM-1 may contribute to the increased
      vascular tone and resistance that compromise circulation.

PMID- 15739257
TI  - Ten-year evaluation of the Regional Core Health Data Initiative.

PMID- 15739256
TI  - Critical appraisal of revised cholesterol guidelines for the very high-risk
      patient.
AB  - A working group from the Adult Treatment Panel III of the national Cholesterol
      Educational Program issued a revised algorithm for low-density lipoprotein (LDL)
      cholesterol lowering in very high-risk cardiovascular disease patients. The
      rationale of these recommendations was primarily established from pooled analysis
      of multiple clinical trials of LDL-cholesterol-lowering therapies and limited
      data from an acute coronary syndrome trial. In the near future, the findings of
      these large-scale randomized trials designed to test the hypothesis that more
      aggressive LDL-cholesterol therapy is accompanied by fewer cardiovascular events
      than less aggressive LDL-cholesterol lowering therapy, will provide the evidence
      needed to support or refute these new recommendations. In this article, the
      authors suggest that an LDL-cholesterol level of less than 70 mg/dl is
      unattainable and not necessary for many high-risk patients. Furthermore, the
      potential risks associated with high-dose statin agents in certain patients, such
      as the elderly, may outweigh these putative benefits.

PMID- 15739258
TI  - Peru.

PMID- 15739259
TI  - Venezuela.

PMID- 15739260
TI  - The significance of responses of the genome to challenge.

PMID- 15739261
TI  - [Surgery of the low extremity varices as a part of a same-day surgery programme].
AB  - INTRODUCTION: One-day surgical methods lower the procedures costs as well the
      need for urgent beds in surgical clinics. The varix operation seem to be the
      optimal diagnosis suitable for the one-day surgical procedure. AIM: The aim of
      this work is to assess a feasibility of the one-day surgery for the low
      extremities varix operations. METHODOLOGY: During the period starting in January
      until December 2003, 98 extremities were operated for varices. The surgical
      procedure was the same for the hospitalized as well as for the patients assigned
      to the one-day surgery programme. Each patient was examined with the duplex
      ultrasound prior to the surgery, after the surgery a compressive bandage was
      indicated. RESULTS: We operated 98 extremities in 96 patients suffering from
      varices during the period from January 2003 to December 2003. The trial group
      consisted of 67 females and 29 males aged 21-79 years of age (the average of 45.3
      years). According to the CEAP classification, 57 extremities (58.2%) were
      assigned to the C2 category, 30 extremities (30.6%) to the C3 category, 6
      extremities (6%) to the C4 category, 4 extremities (4%) to the C5 category and
      one extremity (1%) to the C6 category. 14 extremities in the group were operated
      due to the disease relapse. 62 patients (i.e. 65%) were released for the home
      care on the day of the operation, 27 patients (28%) were released the following
      day. One patient was hospitalized for two days, three patients for three days,
      one patient for four days and two patients for five days. 91 out of the total 98
      extremities (i.e. 93%) underwent the one-day surgery. CONCLUSION: Although some
      patients require hospitalization, the varix surgery is safe and suitable for the
      one-day surgery. A thorough preoperative examination as well each patient's
      cooperation are both very important.

PMID- 15739262
TI  - Transendothelial migration of two metastatic breast carcinoma cells depend on the
      SDF-lalpha-CXCR4 complexes.
AB  - The role of the SDF-1alpha chemokine-CXCR4 receptor system on tumor cell
      transendothelial migration was studied by culturing metastatic breast tumor cell
      lines, MDA-MB-231 and MDA-MB-435, either alone or on a HUVEC monolayer pre
      established on a "Transwell" filter. After a 24-hour culture in the presence or
      absence of SDF-1alpha, tumor cell transmigration rates were compared. We showed
      that: CXCR4 is present on both cell lines; MDA-MB-231 but not MDA-MB-435 cell
      migration is stimulated by increasing concentrations of SDF-1alpha; neutralizing
      anti-CXCR4 antibody inhibits the SDF-1alpha chemoattractant effect; CXCR4
      expression, measured by cytofluorometry, was enhanced after treatment with SDF
      1alpha on MDA-MB-231 cells but remained unchanged on MDA-MB-435 cells; Scatchard
      analysis evidences 8.10(5) and 2.10(5) high affinity sites (KD range: 20 to 30
      nM) on, respectively, MDA-MB-231 and MDA-MB-435 cells. These significant
      differences could explain the distinctive transendothelial migration responses of
      these two cell lines in the presence of SDF-1alpha.

PMID- 15739263
TI  - Expression of MMPs and TIMPs genes in human breast cancer epithelial cells
      depends on cell culture conditions and is associated with their invasive
      potential.
AB  - Growth and invasiveness of breast cancer cells in adjacent and distant sites is
      associated with the expression of metalloproteinases (MMPs), which are capable of
      degrading almost all extracellular matrix macromolecules of supporting stroma. In
      order to identify markers useful for monitoring breast cancer pathogenesis and
      metastatic potential, we examined the expression of mRNAs encoded for MMPs and
      their endogenous inhibitors (TIMPs) in a panel of four epithelial breast cancer
      cell lines of high (MDA-MB-231 and ZR-75-1) and low (MCF-7 and BT-20) metastatic
      potential, and their expression was compared with that of normal mammary cells
      (MCF-12A). Expression patterns were evaluated using cell cultures in serum
      containing and serum-free media. Gene expression studies were performed following
      cell cultures, RNA isolation, reversed transcription and polymerase chain
      reaction. Both normal and breast cancer cells express MMPs and TIMPs at various
      levels, depending on cell type and culture conditions. Comparison of their mRNA
      levels from serum-containing media showed that MMP-9, MT2-MMP and TIMP-1 are
      highly expressed in all cancer cells as compared to normal ones, whereas MMP-1
      and -7 are overexpressed only in breast cancer cells of high invasion potential.
      In serum-free cultures, the highly metastatic cells retain the overexpression
      profile for MMP-1 and -7. Furthermore, MT2-MMP and TIMP-1 were constitutively
      expressed and they can also be correlated with cancer cells, whereas constitutive
      expression of MMP-9 was similar in normal and cancer cells. The results of this
      study indicate that the expression of MMPs is dependent on the culture
      conditions, i.e. the growth factors present in serum-containing media.
      Furthermore, data suggest that, independently of cell culture conditions, the
      expression of MT2-MMP may be associated with malignant transformation of mammary
      cells and the overexpression of MMP-1 and -7 with the highly metastatic potential
      of epithelial breast cancer cells.

PMID- 15739264
TI  - Changes of serum HER2 status during clinical course of metastatic breast cancer
      patients.
AB  - BACKGROUND: Serum HER2 testing allows the determination of the real-time HER2
      status of breast cancer patients. The aim of this investigation was to study (i)
      whether changes of serum HER2 status occur during the clinical course of breast
      cancer and (ii) to evaluate the prognostic significance of serum HER2 status, at
      the time of first diagnosis of primary breast cancer and at the onset of
      metastatic disease, for survival after relapse (SAR). MATERIALS AND METHODS: HER2
      serum levels were retrospectively measured in 152 breast cancer patients at the
      time of first diagnosis of breast cancer and at the onset of metastatic disease
      by enzyme immunoassay. RESULTS: Twenty-seven out of 152 (18%) patients had
      elevated HER2 serum levels at the time of first diagnosis of breast cancer. In
      contrast, 56 out of 152 (37%) patients showed elevated serum HER2 levels when
      metastases were diagnosed. A change of serum HER2 status during clinical course
      was observed in 43 out of 152 (28%) patients. Serum HER2 status at the time of
      first diagnosis of breast cancer had no impact on survival after relapse (SAR) (p
      = 0.4). However, the median SAR for serum HER2-positive patients at the onset of
      metastatic disease was significantly shorter (8 months, 95% CI: 3-12) compared to
      patients serum HER2-negative at this time (18 months, 95% CI: 14-22) (p < 0.01).
      CONCLUSION: Serum HER2 status can change during the course of disease. Therefore,
      the serum HER2 status should be re-evaluated at the time of diagnosis of
      metastatic disease to optimize treatment decisions.

PMID- 15739265
TI  - Research issues in the multiple diagnoses of HIV/AIDS, mental illness and
      substance abuse.

PMID- 15739266
TI  - The HIV/AIDS Treatment Adherence, Health Outcomes and Cost Study: conceptual
      foundations and overview.
AB  - A growing population of people living with HIV/AIDS have co-morbid psychiatric
      and substance abuse diagnoses, increasing the need for integrated services for
      persons with multiple diagnoses. This article reviews models of integrated
      services for multiply diagnosed persons living with HIV/AIDS. We focus on the
      HIV/AIDS Treatment Adherence, Health Outcomes and Cost Study to highlight the
      elements of multifaceted and integrated service delivery systems for people with
      HIV, substance abuse, and mental health disorders. Study organizational features
      and models of integrated services are discussed, including details of models for
      assessing mental health and substance abuse, outcomes, and the cost-effectiveness
      of integrated services.

PMID- 15739267
TI  - Assessing environmental attitudes and concerns about a contaminated site in a
      densely populated suburban environment.
AB  - Considerable attention has been devoted to the concerns and perceptions of people
      residing around contaminated facilities, both brownfields in urban areas and
      others located in remote and lightly populated areas. This paper examines the
      concerns of recreationists and sportsmen residing near the Department of Energy's
      (DOE) Brookhaven National Laboratory, in central Long Island, one of the most
      densely populated regions in the United States, where tourism is of prime
      importance. On an open-ended question, the greatest concern was pollution,
      followed by environmental health as a global concern, and human health as a
      concern for Brookhaven. Accidents/spills, loss of public health, and loss of
      ecological health were rated highest among a list of concerns, and change in
      property values was rated lowest. When asked to rank seven concerns, protecting
      human health was ranked the highest, and economic interests were ranked the
      lowest. For future land use at Brookhaven, recreational uses were rated the
      highest, while building houses and factories, and storage of nuclear material
      were rated the lowest. These data can be used by managers, decision and policy
      makers, and the general public to assess and manage local and regional
      environmental concerns and to consider future land uses for decommissioned lands,
      such as those at Brookhaven.

PMID- 15739268
TI  - Assessment of potential atmospheric transport and deposition patterns due to
      Russian Pacific Fleet operations.
AB  - A probabilistic analysis of atmospheric transport and deposition patterns from
      two nuclear risk sites-Kamchatka and Vladivostok-situated in the Russian Far East
      to countries and geographical regions of interest (Japan, China, North and South
      Koreas, territories of the Russian Far East, State of Alaska, and Aleutian Chain
      Islands, US) was performed. The main questions addressed were the following:
      Which geographical territories are at the highest risk from hypothetical releases
      at these sites? What are the probabilities for radionuclide atmospheric transport
      and deposition on different neighboring countries in case of accidents at the
      sites? For analysis, several research tools developed within the Arctic Risk
      Project were applied: (1) isentropic trajectory model to calculate a multiyear
      dataset of 5-day forward trajectories that originated over the site locations at
      various altitudes; (2) DERMA long-range transport model to simulate 5-day
      atmospheric transport, dispersion, and deposition of 137Cs for 1-day release (at
      the rate of 10(10) Bq/s); and (3) a set of statistical methods (including
      exploratory, cluster, and probability fields analyses) for evaluation of
      trajectory and dispersion modeling results. The possible impact (on annual,
      seasonal, and monthly basis) of selected risk sites on neighboring geographical
      regions is evaluated using a set of various indicators. For trajectory modeling,
      the indicators examined are: (1) atmospheric transport pathways, (2) airflow
      probability fields, (3) fast transport probability fields, (4) maximum possible
      impact zone, (5) maximum reaching distance, and (6) typical transport time
      fields. For dispersion modeling, the indicators examined are: (1) time integrated
      air concentration, (2) dry deposition, and (3) wet deposition. It was found for
      both sites that within the boundary layer the westerly flows are dominant
      throughout the year (more than 60% of the time), increasing with altitude of free
      troposphere up to 85% of the time. For the Kamchatka site, the US regions are at
      the highest risk with the average times of atmospheric transport ranging from 3
      to 5.1 days and depositions of 10(-1) Bq/m2 and lower. For the Vladivostok site,
      the northern China and Japan regions are at the highest risk with the average
      times of atmospheric transport of 0.5 and 1.6 days, respectively, and depositions
      ranging from 10(0) to 10(+2) Bq/m2. The areas of maximum potentially impacted
      zones are 30 x 10(4) km2 and 25 x 10(4) km2 for the Kamchatka and Vladivostok
      sites, respectively.

PMID- 15739269
TI  - Normal childbirth.

PMID- 15739270
TI  - Infant-feeding.

PMID- 15739271
TI  - Biography and the Welsh.

PMID- 15739272
TI  - "Mind control," "synthetic sanity," "artificial competence," and genuine
      confusion: legally relevant effects of antipsychotic medication.

PMID- 15739273
TI  - Regulation of recombinant DNA research: a comparative study.

PMID- 15739274
TI  - Title X, the abortion debate, and the First Amendment.

PMID- 15739275
TI  - Why the unconstitutional conditions doctrine is an anachronism (with particular
      reference to religion, speech, and abortion).

PMID- 15739276
TI  - Synthesis and cytotoxicity of new aminoterpenylquinones.
AB  - Several 6(7)-alkyl-1,4-naphthoquinones (NQ) have been prepared by cycloaddition
      reactions between the monoterpene alpha-myrcene and p-benzoquinones and halogen
      and nitrogen-containing functional groups have been introduced at the C-2
      position of the naphthoquinone ring via nucleophilic addition or substitution
      reactions. These substituents at positions 2/3 of the NQ clearly influence the
      cytotoxic potency of this type of compound. Of particular interest is
      substitution by arylamino, specifically p-oxyarylamino, groups, which
      considerably enhance their bioactivity and selectivity.

PMID- 15739277
TI  - Single-staged double anterior and posterior spinal reconstruction for rigid adult
      spinal deformity: a report of four cases.
AB  - BACKGROUND CONTEXT: Sequential anterior/posterior spinal reconstruction for rigid
      adult spinal deformity has become a standard operative option. Single-staged
      double anterior/posterior spinal reconstruction for rigid double major curvature
      has not been reported in the literature to date. PURPOSE: To report a previously
      unreported approach for rigid double major curvature of the thoracic and
      thoracolumbar spine with emphasis on indications and avoiding complications.
      STUDY DESIGN: Four cases of sequential double anterior/posterior spinal
      reconstruction are reported. METHODS: Single-staged double anterior spinal
      reconstruction was performed on four adult patients with rigid thoracic and
      thoracolumbar scoliosis. Osteotomies were performed by the anterior and posterior
      approach and followed by posterior instrumentation. A right thoracotomy and left
      retropleural/retroperitoneal approach was performed for each patient followed by
      the posterior approach in a single stage. RESULTS: Only one complication
      occurred, a posterior dural tear, treated without incident. A high level of
      patient satisfaction and return to activity was noted. Solid arthrodesis with
      good coronal and sagittal balance occurred in all patients. CONCLUSIONS: Single
      staged double anterior/posterior spinal reconstruction for rigid adult deformity
      can be performed safely and effectively with good patient outcome. The procedure
      should be reserved only for those patients with severe double major curvature of
      similar magnitude and rigidity.

PMID- 15739278
TI  - Image-guided surgery in resection of benign cervicothoracic spinal tumors: a
      report of two cases.
AB  - BACKGROUND CONTEXT: Osseous spinal tumors are an uncommon cause of persistent
      axial pain and muscle spasm, but even benign lesions may grow to cause deformity
      or neurological signs. Traditional treatment approaches to resection can be
      debilitating even when the tumor is benign. PURPOSE: Emerging technologies allow
      surgeons to diagnose and treat osseous neoplasms while minimizing the collateral
      damage caused by surgical exposure and tumor excision. STUDY DESIGN: Technical
      considerations are presented through two cases of benign osseous neoplasm
      occurring in the cervicothoracic spine of competitive athletes, demonstrating the
      meth-ods used to provide effective treatment while maintaining maximal functional
      capacity. METHODS: Stereotactic imaging and intraoperative guidance was used as
      an adjunct to tumor care in these patients. Used in combination with minimally
      invasive, microsurgical techniques,stereotactic guidance localized and verified
      excision margins of benign vertebral lesions, minimizing soft tissue trauma and
      collateral damage. RESULTS: Computer-assisted stereotactic localization allowed
      us to successfully ablate these lesions from their anatomically challenging
      locations, without disrupting the shoulder girdle or neck musculature, and
      without extensive bony resection. CONCLUSIONS: Image guidance can accurately
      localize and guide excision of benign vertebral lesions while minimizing soft
      tissue trauma and collateral damage, allowing patients a rapid and complete
      return to high-demand function.

PMID- 15739280
TI  - Spinal cord injury changes caudal segmental spinal cord excitability resulting in
      changes to spinal cord signal processing and modulation of late response
      recordings.

PMID- 15739279
TI  - Glivec and CML: a lucky date.
AB  - Chronic Myeloid Leukemia (CML) has always been an ideal model to understand the
      molecular pathogenesis of human leukaemias and the way to cure them. This can be
      ascribed to the fact that CML was the first human cancer demonstrated to be
      strongly associated to the presence of a recurrent chromosomal translocation (the
      t(9;22)(q34;q11) that creates the Philadelphia (Ph)-chromosome) and to a specific
      molecular defect, the formation of a hybrid BCR-ABL gene that generates new
      fusion proteins endowed with a constitutive tyrosine-kinase (TK) activity,
      strongly implicated in the pathogenesis of the disease. The introduction into
      clinical practice of imatinib, (Glivec, Gleevec, Novartis), a potent tyrosine
      kinase inhibitor of the Bcr-Abl protein as well as of a restricted number of
      other TKs, has not only produced a substantial improvement in the treatment of
      CML, but represents a major break-through in the perspective of opening a new
      era, that of molecularly targeted therapy, in the management of other types of
      leukemia, lymphoma and cancer in general.

PMID- 15739281
TI  - When advanced techniques are needed to confirm a commonplace diagnosis.

PMID- 15739282
TI  - Bounding the risk of crew loss following orbital debris penetration of the
      International Space Station at assembly stages 1J and 1E.
AB  - Orbital debris impacts on the International Space Station occur frequently. To
      date, none of the impacting particles has been large enough to penetrate manned
      pressurized volumes. We used the Manned Spacecraft Crew Survivability code to
      evaluate the risk to crew of penetrations of pressurized modules at two assembly
      stages: after Flight 1J, when the pressurized elements of Kibo, the Japanese
      Experiment Module, are present, and after Flight 1E, when the European Columbus
      Module is present. Our code is a Monte-Carlo simulation of impacts on the Station
      that considers several potential event types that could lead to crew loss. Among
      the statistics tabulated by the program is the probability of death of one or
      more crew members in the event of a penetration, expressed as the risk factor, R.
      This risk factor is dependent on details of crew operations during both ordinary
      circumstances and decompression emergencies, as well as on details of internal
      module configurations. We conducted trade studies considering these procedure and
      configuration details to determine the bounds on R at the 1J and 1E stages in the
      assembly sequence. Here we compare the R-factor bounds, and procedures could that
      reduce R at these stages.

PMID- 15739283
TI  - Medical philosophy and medical ethics.

PMID- 15739284
TI  - Is allowing someone to die the same as murder?

PMID- 15739285
TI  - Medical decision-making for children and the question of legitimate authority.

PMID- 15739286
TI  - HIV vaccine trials: critical issues in informed consent.
AB  - Informed consent (IC), a fundamental principle of ethics in medical research, is
      recognized as a vital component of HIV vaccine trials. There are different
      notions of IC, some legally based and others based on ethics. It is argued that,
      though legal indemnity is necessary, vaccine trials should be founded on fully
      ethical considerations. Various contentious aspects of IC are examined,
      especially the problem of social desirability and of adequate comprehension. The
      need for sensitivity to cultural norms in implementing IC procedures is
      critically reviewed, and some of the potential conflict between ethos and ethics
      is considered. The transmission of information is examined as a particular aspect
      of IC in HIV vaccine trials.

PMID- 15739287
TI  - Ethical considerations in apathy syndromes.

PMID- 15739288
TI  - Ethical and legal dimensions of benzodiazepine prescription: a commentary.

PMID- 15739289
TI  - 'He found me very well; for me, I was still feeling sick': the strange worlds of
      physicians and patients in the 18th and 21st centuries.
AB  - It is commonplace today to deplore the dissatisfaction of patients with the
      physician-patient relationship. Furthermore, historical investigation shows that
      this problem is not really new. We investigated an important source of patients'
      views in the 18th century, namely the letters of patients received by the famous
      Swiss physician, Samuel Tissot, and noted remarkably similar feelings of
      frustration. Yet the medical paradigms of today and of Tissot's times are
      considerably different. We propose that the persisting problems in the physician
      patient relationship are due to a basic dissonance between the patient's ordinary
      modes of perception and the systematic way of perceiving reality characteristic
      of the physician. In addition, they reflect the unavoidable chasm between the
      ultimately private and singular nature of the illness experience, and the general
      and anonymous stance of medical theory. This chasm is therefore a permanent
      feature of the patient-physician relationship, predating the advent of scientific
      medicine, even if the latter reinforced it. In line with the current medical
      humanities movement, we believe that the engagement of physicians and medical
      students with literature and the arts helps them explore, and to some extent
      overcome, the existential divide between the patient's experiential self
      knowledge and the systematic, impersonal knowledge that plays a central role in
      medicine. We suggest a few examples of contemporary fiction that may be relevant
      and useful in this respect.

PMID- 15739290
TI  - Medical facilities as moral worlds.
AB  - Bioethics is dominated by an emphasis on rule making and quandary solving.
      Teaching and research in ethics often focuses upon dramatic, controversial issues
      at the margins of life and death. Much less attention is given to the
      relationship between moral reflection and the ethos of place. Medical facilities,
      however, are moral worlds. To discuss the ethos of place is to focus on the
      character or atmosphere of particular dwellings. Architecture, interior design,
      and the interior creation of built environments have moral, spiritual, and
      aesthetic dimensions. Discussions of "ethics" need to be less oriented to rules
      and dilemmas, and more attuned to practical matters of everyday social
      experience. Instead of developing all-encompassing critiques of medical
      facilities as impersonal, alienating institutions, scholars from various fields
      need to explore the incremental steps that can make particular settings more
      decent, humane, and caring.

PMID- 15739291
TI  - Ethics and the practice of rehabilitation counselor supervision.
AB  - The ethical issues inherent in rehabilitation counselor supervision are
      discussed. More specifically, the following topics are addressed: (a) emerging
      ethical standards in rehabilitation counseling supervision, (b) supervisory
      relationship vulnerability and codes of ethics applicable to rehabilitation
      supervision, and (c) ethical concerns that are common to supervision.

PMID- 15739292
TI  - Profit and the patent on life.

PMID- 15739293
TI  - Tyranny at the two edges of life: a liberal view. Interview by Nathan Gardels.

PMID- 15739294
TI  - Immoral clones: a Vatican view.

PMID- 15739295
TI  - Human clones and God's trust: an Islamic view.

PMID- 15739296
TI  - Descartes, brain death and organ transplants: a Japanese view.

PMID- 15739297
TI  - My obsession with life. Interview by Jack Lessenberry.

PMID- 15739298
TI  - Brave new biocracy: health care from womb to tomb.

PMID- 15739299
TI  - Time of closure of cranial sutures in northwest Indian adults.
AB  - Time of closure of sagittal, coronal and lambdoid sutures was studied at autopsy
      in 538 male and 127 female adults of known ages belonging to Chandigarh zone of
      northwest India. The sagittal suture was divided into four segments and each side
      of the coronal and lambdoid sutures into three segments. Whether a segment was
      open or closed on either surface was recorded. On analysing the record, the
      authors came to the conclusions: (1) obliteration of sutures commences earlier in
      the males than in females, (2) suture obliteration starts earlier on endocranial
      surface than on the ectocranial and (3) commencement and complete obliteration of
      a segment or the entire suture is so erratic that it is not useful for estimating
      the age of a skull.

PMID- 15739300
TI  - Bioethics and conflicting ethical criteria.
AB  - Some of the major problematic issues in contemporary ethical discourse are
      highlighted in the field of bioethics. The need to incorporate new understandings
      and foundational shifts in essential criteria because of technological advances
      in the areas of medicine and human sciences increasingly challenges traditional
      and accepted notions of ethics. As the possibilities of technical progress
      increase, more and more pressure is put on traditional understandings of the
      human person, identity, and value. In the face of ethical relativism and
      emotivism, which are already widespread in social and political discourse, the
      immediacy of bioethics as a response to technology and its impact on human lives
      reinforces the need for ethics to become interdisciplinary, while attempting to
      provide some coherence to both the questions and the responses that contemporary
      life generates. In this paper, the author intends to sketch the outlines of some
      of these problems, and suggest one approach which might allow a certain
      methodical intelligibility to emerge which takes into account shifts in
      consciousness and the dependence on historically grounded perspective.

PMID- 15739301
TI  - Genetics and bioethics: the current state of affairs.
AB  - The pursuit of genetic knowledge has such emotional, social, scientific, and
      financial importance that it has been compared to the divine quest for the Holy
      Grail, and to the calamity of opening Pandora's Box. Therefore, it comes as no
      surprise that the recent announcement of a completed blueprint for the human
      genome has fueled calls for both increased research and increased precautions.
      This new era, which holds the potential promise of advances in medicine,
      agriculture and other areas, also requires the careful investigation of a myriad
      of issues. Those issues such as informed consent, patenting, privacy, and
      confidentiality, have been explored in at least some detail. Others, such as
      equity, mutual respect, empowering education, consensus building, and planning
      for long-term survival, have not been as fully examined, nor have they been as
      comprehensively integrated into mainstream thinking. To facilitate this, we need
      to implement an ethical approach that leads us to ask critical questions about
      the appropriate use of our new tools.

PMID- 15739303
TI  - Learning from the Dutch: physician-assisted death, slippery slopes and the Nazi
      analogy.

PMID- 15739302
TI  - Euthanasia and law in the Netherlands: reflections on Dutch perspectives.
AB  - During the summer of 1999, twenty-eight interviews with some of the leading
      authorities on the euthanasia policy were conducted in the Netherlands. The
      discussion begins with providing some background information on the guidelines
      for conducting euthanasia. Next, I explain the research methodology and move on
      to discuss the interviewees' responses to the question whether it is preferable
      to legislate euthanasia. The interviewees exhibited split views on the issue.
      Some were in favor of legislation for instrumental and symbolic reasons. Others
      utilized different instrumental and symbolic reasons to argue against
      legislation. Three interviewees preferred to wait for some years before changing
      the law.

PMID- 15739304
TI  - Brickbats and bouquets for the draft legislation on assisted human reproduction.

PMID- 15739305
TI  - Community-based research ethics review: reflections on experience and
      recommendations for action.

PMID- 15739306
TI  - The UK model: setting the standard for embryonic stem cell research?

PMID- 15739307
TI  - The report of the committee of inquiry on the case involving Dr. Nancy Olivieri:
      a fiduciary law perspective.

PMID- 15739309
TI  - Conflict of interest in clinical research: direct payment to the investigators
      for finding human subjects and health information.
AB  - The recent death of teenager Jesse Gelsinger in a drug therapy trial has drawn
      attention to how financial conflicts of interest may compromise patient
      protection. While research institutions throughout the world have instituted a
      variety of conflict of interest guidelines, the potential conflicts associated
      with investigators receiving direct payment from private companies for both the
      recruitment of patients and the running of clinical trials in pharmaceutical
      research remains a relatively unexplored area. Clinical researchers undoubtedly
      deserve to be reasonably compensated for their participation. But these incentive
      mechanisms also have the potential to create conflicts of interest--both real and
      perceived.

PMID- 15739308
TI  - Submission on draft legislation on assisted human reproduction.

PMID- 15739310
TI  - Implications of nanotechnology applications: using genetics as a lesson.

PMID- 15739311
TI  - The science of stem cells: some implications for law and policy.

PMID- 15739312
TI  - Regulating the creation of novel beings.

PMID- 15739313
TI  - Bill C-13 The Assisted Human Reproduction Act: examining the arguments against a
      regulatory approach.

PMID- 15739314
TI  - Defining a policy rationale for the criminal regulation of reproductive
      technologies.

PMID- 15739315
TI  - A constitutional analysis of the proposed ban on non-reproductive human cloning:
      an unjustified violation of freedom of expression?

PMID- 15739316
TI  - Donate a definition.

PMID- 15739317
TI  - Betwixt and between human stem cell guidelines and legislation.

PMID- 15739318
TI  - Mum's the word: donor anonymity in assisted reproduction.

PMID- 15739319
TI  - Privacy and assisted human reproduction: a discussion paper.

PMID- 15739320
TI  - Stem cell terminology: practical, theological and ethical implications.
AB  - Stem cell policy discussions frequently confuse embryonic and fetal sources of
      stem cells, and label untested, non-reproductive cloning as "therapeutic." Such
      misnomers distract attention from significant practical and ethical implications:
      accelerated research agendas tend to be supported at the expense of physical
      risks to women, theological implications in a multi-faith community, informed
      consent for participation in research, and treatment decisions altered by
      unrealistic expectations.

PMID- 15739321
TI  - International initiatives.

PMID- 15739322
TI  - [The use of enthalpy-entropy compensation in the study of retention mechanism of
      aromatic positional isomers].
AB  - In this paper, the thermodynamic parameters of the separation process of six
      groups of aromatic positional isomers on nine crown ether polysiloxane, OV-1701
      and Carbowax-20M capillary chromatographic columns have been investigated
      systematically. The Gibbs free energies for every compound at harmonic mean
      temperature, calculated were given. The enthalpy-entropy compensation effect of
      these chromatographic process was examined by using of Krug's ANOVA method. In
      the light of the axiom of extrathermodynamic relationship, the retention
      mechanisms of these aromatic compounds on each crown ether stationary phase have
      been expounded. We come to conclusion that, as a whole, the separation of various
      aromatic isomers on crown ether stationary phase is governed by multiple
      retention mechanisms, but the separation of some groups of aromatic isomer on the
      same crown ether phase can be led to single interaction mechanism since the
      phenomena of enthalpy-entropy compensation is observed. It may be that a kind of
      interaction parameter, which varies with the configuration of solutes, plays the
      main role in retention process of these isomers.

PMID- 15739323
TI  - [Identification of photoproducts for PCB congeners by the new retention index
      system].
AB  - Polychlorinated biphenyls (PCBs) are a kind of priority pollutants, constituting
      a complex group of 209 congeners ranging from monochloro to decachlorobiphenyls.
      Because of the shortcomings of retention time data and the lack of suitable
      retention index systems, the congeners analysis of PCBs is one of the most
      challenging tasks in capillary column gas chromatography (GC), especially due to
      the fact that the isomers of PCBs can not be identified by GC-MS. A new retention
      index system, suitable for analysis of PCB congeners in the environmental samples
      by temperature-programmed capillary gas chromatography with ECD, has been
      developed recently by Chu et al. In this paper, retention indexes of all 209 PCB
      congeners were calculated according to the new retention index system from their
      respective retention times reported by other authors. The photoproducts of PCB87,
      PCB138 and PCB169 were identified with the new retention index system and
      confirmed by GC-MS. The deviations of retention indexes for all photoproducts
      were within 3 index units. It was testified that the above retention index system
      was reliable during the identification of PCB congeners and would have wide
      applicability. Based on the formations of coplanar PCB congeners (PCB77 and
      PCB126) during the photodegradations of PCB138 and PCB169, it was proposed that
      toxic equivalence (TEQ) should be used as a kind of quality indicator for the
      studies of the photolysis of PCBs.

PMID- 15739324
TI  - [Analysis of triacylglycerol composition of perilla oil by combination of non
      aqueous reversed-phase high performance liquid chromatography with gas
      chromatography].
AB  - Perilla oil was verified to be a rich source of polyunsaturated fatty acid
      (PUFA). Its linolenic content is 64.82%, the highest in the plants. Its
      triacylglycerol (TAG) components were isolated and identified first time in this
      paper by a combination of non-aqueous reversed-phase high performance liquid
      chromatography (RP-HPLC) with gas chromatography (GC). The TAG of perilla oil
      were isolated by HPLC with a Zorbax ODS column (5 microm, 4.6 mm i.d. x 250 mm;
      Dupont, Inc) and differential refractometer. The eluent was acetone/acetonitrile
      (80:20, V/V) with flow rate of 1.0 mL/min. The TAG component acyl groups were
      converted to fatty acid methyl esters (FAME). The acyl constituents for each TAG
      were determined by GC analysis. Gas chromatography of FAMEs was performed with a
      AC20 Carbowax 20M column (30 m x 0.32 mm i.d.). Detector and injection port
      temperatures were 260 degrees C. Column temperature was programmed from 120
      degrees C, 1 min initially hold, then 8 degrees C/min to 220 degrees C and
      finally hold for 10 min. Nitrogen was the carrier gas. FAMEs peaks were
      identified by comparison of their retention times with those of standards. The
      retention times of the palmitic, stearic, oleic, linoleic, n-nonadecanoic acid
      (internal standard) and linolenic FAMEs were 10.7, 13.0, 13.3, 13.8, 14.2 and
      14.7 min respectively. Five main components were determined. They were LnLnLn
      (34.10%), LnLnL (13.22%), LnLL (6.22%), LnLnO (11.38%) and LnLnP (9.17%). The TAG
      contents were corrected from their fatty acids content. The combination of non
      aqueous RP-HPLC with GC is a simple and rapid method for the analysis of oil TAG
      structure and is also very helpful for the identification of oil quality.

PMID- 15739325
TI  - [Determination of glutamine in intestinal mucosa by pre-column
      derivatization/reversed-phase high performance liquid chromatography with
      fluorescence detection].
AB  - A high performance liquid chromatographic pre-column derivatization method with
      fluorescence detection for the analysis of glutamine (Gln) in rat intestinal
      mucosa is presented. Gln was derivatized with o-phthalaldehyde and 3
      mercaptopropionic acid under an alkaline condition and separated by reversed
      phase liquid chromatography on a Lichrosorb RP18 column (150 mm x 4.6 mm i.d., 5
      microm). The mobile phase was consisted of 50 mmol/L phosphate buffer (pH 7.0)
      acetonitrile (94:6, V/V) with a flow rate of 2.0 mL/min. The excited and emitted
      wavelength were selected at 230 nm and 389 nm respectively. The volume ratio of
      samples and derivatization reagent solution was 4:1 (V/V). The detection limit of
      Gln was 25 micromol/L (S/N= 3.5) and the regression equation was A = 16.9405C +
      179.9339, r = 0.9996 at the linear range of 50-3200 micromol/L. The day-to-day
      deviation was 6.97% (n = 3) and the retention time of Gln was 3.158 min. This
      method is rapid, simple and highly sensitive, and has been applied to the
      determination of Gln in intestinal mucosa.

PMID- 15739326
TI  - The retention behavior of arsenic compounds on PRP-X100 column under alkaline
      condition.
AB  - A systematical investigation of the retention behaviour of arsenic compounds
      (arsenite, arsenate, methylarsonic acid, dimethylarsinic acid, arsenobetaine
      etc.) on PRP-X100 column under alkaline condition was carried out. The dependence
      of the retention times of arsenic compounds on pH with two mobile phases: 20
      mmol/L ammonium bicarbonate, 2.5 mmol/L p-hydroxybenzoic acid/1.0 mmol/L benzoic
      acid was studied, and the optimal separations of these five arsenic compounds
      were achieved.

PMID- 15739327
TI  - [Separation and determination of plant growth regulators by capillary micellar
      electrokinetic chromatography].
AB  - It is important for separation and determination of plant growth regulators in
      the research of plant physiology. A study of the separation of five plant growth
      regulators, such as abscisic acid (ABA), gibberellic acid (GA), indole-butyric
      acid (IBA), indole acetic acid (IAA) and naphthaleneacetic (NAA) by micellar
      electrokinetic chromatography (MEKC) is presented. The effects of pH, SDS
      concentration, applied voltage and organic additives on migration behavior were
      investigated. Results showed that satisfactory separation was achieved on
      optimization of electrophoretic condition: 80 mmol/L SDS, 10 mmol/L borate
      phosphate, 5% isopropanol, 18 kV applied voltage, pH 8.0. The SDS concentration
      and organic additives played an important role in separating plant growth
      regulators, and the applied voltage and pH gave less effect. The detection limit
      of ABA, GA, IBA, IAA and NAA were 5.0 x 10(-3), 3.0 x 10(-3), 5.8 x 10(-4), 1.5 x
      10(-4) and 1.4 x 10(-4) g/L respectively. Increasing of the SDS concentration or
      organic additives would change separation factor (alpha) and result an
      improvement of the resolution of difficult separation pairs ABA-GA and IAA-NAA.

PMID- 15739328
TI  - [Developments and applications of perfusion chromatography].
AB  - This review deals with the developments and applications of perfusion
      chromatography proposed recently by Afeyan and its related techniques. The review
      with 40 references involves characteristics, theories and applications of
      perfusion chromatography.

PMID- 15739329
TI  - [The combinations of separation modes in multidimensional high performance liquid
      chromatography (MDHPLC)].
AB  - MDHPLC is a new chromatographic technique, in which fractions from a separation
      system are selectively transferred to one or more secondary chromatographic
      systems with different separation mechanism to enhance resolution and
      sensitivity, or to decrease analysis times. In this review, the principle,
      characteristics and developments of MDHPLC are discussed. The various possible
      combinations of separation modes in HPLC [such as, size exclusion
      chromatography/reversed-phase chromatography (SEC/RPC), ion exchange
      chromatography/reversed-phase chromatography (IEC/RPC), normal bonded phase
      chromatography/reversed-phase chromatography (NPC/RPC), size exclusion
      chromatography/ion exchange chromatography (SEC/IEC), liquid-solid
      chromatography/reversed-phase chromatography (LSC/RPC), affinity
      chromatography/reversed-phase chromatography (AC/RPC) and achiral column/chiral
      column] and their applications are systematically reviewed with 63 references.

PMID- 15739330
TI  - [Lecture of principles and applications of capillary electrophoresis (V)
      Applications of capillary electrophoresis in pharmaceutical analysis and clinical
      chemistry].
AB  - A review with 68 references is presented on the application and new developments
      of CE in pharmaceutical analysis, clinical chemistry and single cell analysis
      etc. The pharmaceutical analysis includes main component assay, determination of
      drug-related impurities, stoichiometric determination and quantitative
      determinations. The Chinese herb analysis includes determinations of main
      components and prescriptions of Chinese herb. The chiral separation includes
      separation mechanism and some new chiral selectors. The application of CE in
      clinical chemistry includes determinations of serum and protein, monitoring of
      drug metabolism, etc. Single cell analysis includes determinations of component
      in neurocells and human erythrocyte.

PMID- 15739331
TI  - [Microwave extraction technique].
AB  - A new microwave aided extraction (MAE) technique is introduced in this paper. It
      gives the extraction method as well as reagents, equipment and conditions used in
      the technique. In temperature controlled pressurized vessels, polar solvent (eg.
      acetone) and the combinations of polar and non-polar solvents can be heated to
      approximately 100 degrees C above their normal boiling points. It is told that
      the higher the extraction temperature the more the recovery is. The ratio of
      polar to non-polar solvents affects not only the microwave heating rate but also
      the extraction recovery. The highest recovery ratios are gotten at the solvent
      ratio of three parts of acetone to two parts of hexane. We can see from the
      pesticides chromatogram with MAE, that very little break-down of endrin or DDT
      are detected and they are well below the EPA specified tolerance limits. We can
      find from the comparison of MAE with sonication and Soxhlet extraction techniques
      that microwave extraction technique has not only higher average recoveries (%)
      but also good precision (RSD, %). The data and comparison results illustrate that
      the microwave extraction is a rapid method (about 15 minutes) with less solvent
      consumption (about 30-50 mL), good recovery, and easy to be controlled
      automatically in comparison with the Soxhlet extraction, sonication and other
      extraction methods.

PMID- 15739332
TI  - [Characterization of slowly-growing mycobacteria species by capillary gas
      chromatography].
AB  - A method for the characterization of mycobacteria species by capillary gas
      chromatography is described. After strains of mycobacteria being hydrolyzed,
      saponified in an acidic solution, various methyl esters resulted from
      mycobacteria were studied on an OV-101 column at optimum chromatographic
      conditions. The constituents of 9 slowly-growing mycobacteria species were
      analyzed and the results showed that there were obvious differences between
      different mycobacteria species, but same characteristics were observed between
      strains of the same species. The 9 species can be identified by the ratio of peak
      height of C18:1, C18:0 and TBSA. They are C18:1>TBSA>C18:0 for M. tuberculosis,
      C18:0>C18:1>TBSA for M. triviale, TBSA>C18:1>C18:0 for M. intracellulare,
      TBSA>C18:0>C18:1 for M. avium and C18:1>C18:0>TBSA for M. bovis, M. kansasii, M.
      gordonae, M. nonchromogenicum and M. terrae respectively. The 5 latter species
      can be distinguished by the presence of characteristic peaks of iC16:1 and C19:0.
      75 strains of clinical isolated mycobacteria were analysed at the same
      chromatographic conditions. The results showed that they belonged to 9 different
      species. The accuracy of the proposed method was examined according to biological
      analysis.

PMID- 15739333
TI  - [Determination of total organic acids in wine by interfacial derivatization gas
      chromatographic method].
AB  - This paper presents a new method for analysis of total organic acids in wine as
      follows: organic acids in wine were separated and enriched with strong anion
      exchange resin and were esterified directly on the resin with BF3-diethylether
      and alcohol for 60 min under the temperature of 90 degrees C. The ethyl esters of
      organic acids were extracted with dichloromethane and determined by HP 5890A GC
      5970B MSD equipped with fused-silica capillary column, 12.5 m x 0. 2mm i.d.. The
      column temperature was programmed from 30 degrees C to 60 degrees C at 2 degrees
      C/min, 60 degrees C to 180 degrees C at 5 degrees C/min, 180 degrees C to 230
      degrees C at 10 degrees C/min. Twenty one peaks of ethyl esters of organic acids
      in wine were identified with gas chromatography/mass spectrometry and quantitated
      with internal standard and working curve. The results of analysis are
      satisfactory. This paper has provided a useful method of determination of low
      content of organic acids in complex aqueous samples.

PMID- 15739334
TI  - [Determination of aniline derivatives in waste water with reversed-phase high
      performance liquid chromatography].
AB  - A reversed-phase high performance liquid chromatographic method for the
      determination of aniline derivatives in waste-water is described. Chromatographic
      conditions were: column, Hypersil BDS (200 mm x 4.0 mm i.d., 5 microm); mobile
      phase, methanol-water, gradient elution; flow rate, 1.0 mL/min; detection
      wavelength, 254 nm. Quantification was carried out based on the external standard
      of aniline derivatives. The pH of waste water sample was adjusted to 11-12 with
      dilute NaOH solution prior to extraction with CH2Cl2. The extractives
      concentrated in K-D concentrator and filtered with FH 0.5 microm membrane.
      Finally make up the volume to 1 mL and test it with reversed-phase high
      performance liquid chromatography. The linearity range of calibration curve used
      was 0.005-0.3 microg. The minimum detectable quantities of aniline derivatives
      varied from 1.20 ng to 3.00 ng. The average recoveries were from 51.57% to
      107.92%, and the RSDs of the method were from 1.88% to 5.98%. The method is
      simple, rapid, and accurate.

PMID- 15739335
TI  - [Determination of cefotaxime in human serum by high performance liquid
      chromatography (HPLC)].
AB  - A reversed-phase HPLC assay has been developed for measuring cefotaxime (CTX) in
      human serum. A solid-phase extraction column (Bond Elute C18) was used for the
      pre-purification of sample. Serum (200 microL) was mixed with 100 microL of
      internal standard (acetylamino phenol) solution and 200 microL of sodium acetate
      buffer (0.01 mol/L, pH 5.8), loaded onto the conditioned column and washed with 2
      mL of acetate buffer, the compounds were eluted with 0.5 mL x 2 of methanol
      acetate buffer (40:60, V/V ). The eluate (20 microL) was injected directly into
      an Apex ODS column (250 mm x 4.6 mm i.d., 5 microm) with a mobile phase of
      acetate buffer (0.01 mol/L, pH 5.8)-methanol (80:20, V/V ), detection was
      achieved at 254 nm. The average extraction recoveries were 96.7% and 97.7% for
      CTX and internal standard respectively, which were higher than that of CTX
      (91.0%) obtained by protein precipitation with methanol. The solid-phase
      extraction method also provided much clearer samples for HPLC analysis. The
      concern of acid degradation of CTX when an acid is used as a protein
      precipitation agent was avoided. The calibration curve of CTX was linear between
      10 and 150 mg/L of serum concentration with a correlation coefficient of 0.9992,
      and the minimum detection limit was 2 mg/L. The precision was tested with three
      sample concentrations, and within-day RSD below 3.0% and day-to-day RSD below
      4.1% were achieved. Maximum serum concentrations of 25.95 and 22.89 mg/L were
      measured at 45 min after intramuscular injection of 1 g CTX to two healthy
      volunteers respectively. The chromatographic behaviour of CTX was also studied.

PMID- 15739336
TI  - [Determination of plasma drug concentration and bioavailability of indomethacin
      controlled release capsule by high performance liquid chromatography].
AB  - A simple, rapid, sensitive and accurate reversed-phase high performance liquid
      chromatographic (RP-HPLC) method for the determination of indomethacin in plasma
      is established. To 1 mL of plasma were added 200 microL of amobarbitone solution
      (internal standard; 1 g/L), 100 microL of phosphate buffer solution (pH 7.0), 100
      150 mg of sodium chloride and 2.5 mL of ethyl acetate. The mixture was vortex
      mixed for 10 min and centrifuged at 3000 r/min for 5 min. The organic layer was
      evaporated to dryness at 50 degrees C on water-bath and the residue was dissolved
      in methanol (100 microL). A 20 microL portion of the resulting solution was
      analysed by HPLC on a column (25 cm x 4.6 mm) of micro-Bondapak C18 (10 microm)
      with 76% methanol in 0.035 mol/L phosphoric acid (pH 5.5) aq-solution as mobile
      phase (1 mL/min) and UV detection at 260 nm. The column temperature was 30
      degrees C. Within the range of 0.125-50 mg/L of indomethacin there was a good
      linearity (r = 0.9996). The mean recovery of indomethacin was 100.4%. The
      detectable limit was 62.5 microg/L (S/N = 3:1). The within day and day-to-day RSD
      were less than 5% at three drug levels. This method has been used to determine
      plasma drug concentration and bioavailability of indomethacin controlled release
      capsule for healthy volunteers.

PMID- 15739338
TI  - [Analysis of the pyridinoline and deoxypyridinoline in urine by reversed-phase
      high performance liquid chromatography (RP-HPLC)].
AB  - A method for the simultaneous and rapid determination of pyridinoline and
      deoxypyridinoline in urine using RP-HPLC has been established. After hydrolysis
      for 18 hours at 107 degrees C in 6 mol/L HCl, the urine sample was
      prefractionated by partition chromatography using a column packed with cellulose
      CF1. The appropriate fractions were freeze-dried. The samples were analyzed by
      HPLC with a 5 microm Spherisorb C18 column, a mobile phase of MeOH/H2O containing
      0.1% heptafluorobutyric acid at a rate of 1.2 mL/min and fluorescence detector
      monitoring at lambda(ex) 290 nm and lambda(em) 400 nm. The limit of a detection
      for PYD was 10 nmol/L and DPD 7 nmol/L. The recovery of PYD was 91.5% and that of
      DPD was 106.1%. Within day CV for the two compounds were 1.39% and 0.16%
      respectively and day-to-day CV 3.71% and 1.32% respectively.

PMID- 15739337
TI  - [Determination of demethylvancomycin in neonate serum by high performance liquid
      chromatography].
AB  - A rapid high performance liquid chromatography for determination of
      demethylvancomycin in neonate serum has been developed. The procedure involved a
      simple protein precipitation by acetonitrile-isopropanol (1:1) and then the
      sample was chromatographed on a reversed phase C18 column with UV detection at
      236 nm. The mobile phase was CH3CN: 0.05 mol/L KH2PO4 = 8:92 (V/V). The
      calibration curve was Y = 35,721.89X - 13,031.54, r = 0.9998 and he detection
      limit was 0.3 mg/L. The average recovery was 94.7% +/- 1.2%. Intra-day and inter
      day RSD were 2.23% and 2.62% respectively. It can be concluded that this method
      meets the requirement for routine clinical application. This method has been used
      to determine serum concentration of demethylvancomycin in neonates. The data
      obtained showed that the method was simple, rapid, sensitive and precise.

PMID- 15739339
TI  - [The enrichment of polycyclic aromatic hydrocarbons in water samples by solid
      phase extraction].
AB  - Solid-phase extraction (SPE) is an emerging chromatographic sample preparation
      technique. The novel extraction technique can reduce the time and volume of
      organic solvents required, and alleviate problems associated with the formation
      of emulsions as compared to conventional liquid-liquid extractions. This study
      was designed to demonstrate the utility of SPE for trace enrichment of polycyclic
      aromatic hydrocarbons (PAHs) in water samples. The results showed that
      dichloromethane and benzene are the preferred elution solvents for the adsorbed
      PAHs. The recoveries of PAHs with SPE are in the range of 87% to 102%. When the
      elution solvent is selected, the variation of recoveries as a function of the
      volume of elution solvent used can be determined. Meanwhile, further studies
      showed that recoveries become worse as the number of rings of PAH increased. The
      decrease of solubility and adsorption onto container surface may be responsible
      for bad recoveries. The addition of 20% (V/V) methanol or ethanol into the sample
      prior to spiking can greatly improve the recoveries of larger PAHs. Recoveries of
      89%-108% can be obtained.

PMID- 15739340
TI  - [Selective extraction of organotin from biological sample by supercritical fluid
      extraction].
AB  - The preliminary separation and concentration of organotin compounds from the
      matrix of biological samples is necessary, due to the very low content of
      organotin and the fat included in samples will largely interfere the analysis of
      organotins. In this work, supercritical fluid extraction (SFE) for the
      preliminary separation and concentration of organotin has been studied. Pure CO2
      was used as mobile phase. The extractives can be used to supercritical fluid
      chromatographic (SFC) analysis of organotins. The model sample was prepared by
      adding diphenyltin (DPT) to soya powder. The effects of the pressure and
      temperature on SFE were investigated. A small amount of fat was also extracted
      together with organotins. Extract was injected into SFC system, in which a
      Kapcell Pak ODS column was used for separation of organotin and fat. The effect
      of pressure on the extraction percentage of DPT and fat was investigated at 40
      degrees C. At lower pressure (10-15 MPa), a maximum extraction efficiency (63%)
      was attained for DPT, while the fat is extracted only 28.3%. The increase in
      temperature is advantageous for the selective extraction of DPT. However, the
      extraction efficiency of DPT decreased as the extraction temperature was
      increased. When a lower pressure (10 MPa) and a higher temperature (50 degrees C)
      were used, the organotin (DPT) was extracted up to a maximum (59.9%) within 30
      min, while fat was extracted only 4.9%.

PMID- 15739341
TI  - [Separation of soybean agglutinin by hydrophobic-interaction chromatography].
AB  - The soybean agglutinin (SBA) was separated with hydrophobic-interaction
      chromatography (HIC) in this work. HIC of the crude lectin extract of SBA was
      performed on Phenyl-Sepharose CL-4B column, 10 cm x 2.5 cm i.d., at a flow-rate
      of 1.0 mL/min. A 20 mL sample of the crude extract was applied to the column
      previously equilibrated with the buffer, 0.01 mol/L PBS containing ammonium
      sulfate (60% of saturation concentration). The column was eluted with the
      starting buffer, then with the buffer containing 30% saturation of ammonium
      sulfate, and finally with 0.01 mol/L PBS. Fractions were detected by UV
      absorbance at 280 nm and assayed for hemagglutinating activity. The results show
      that the purification-fold was as high as 35 and the recovery of activity was
      100%.

PMID- 15739342
TI  - [Tailed normal chromatographic peak expressed by plate model].
AB  - An equation for describing tailed normal chromatographic peak is derived based on
      the plate model. In terms of the de Moivre-Laplace theorem, which states that a
      binomial distribution can be approximated by the Gaussian distribution for large
      sample size, it is suggested that the concentration distribution along the
      distance downstream from the inlet of chromatographic column conforms to the
      Gaussian distribution function, but the concentration distribution with elution
      volume (or elution time) does not. The equation developed here, which is similar
      to the Gaussian distribution function, indicates that the normal chromatographic
      elution curve should be a tailing one. It is also shown that the symmetric
      Gaussian elution curve is an approximate solution of the plate model and can be
      obtained by the approximation of the equation here. The equation is proved to be
      congruent to the results of the diffusion model. Thus, the plate model and
      diffusion model are equivalent to each other in describing chromatographic
      process although different mechanism is based on.

PMID- 15739343
TI  - [Simultaneous determination of five carotenoids in tomato by reversed-phase high
      performance liquid chromatography].
AB  - A reversed-phase high performance liquid chromatographic method for the
      simultaneous determination of alpha-carotene, beta-carotene, gamma-carotene,
      lycopene and canthaxanthin in tomato has been developed. These carotenoids were
      extracted with acetone and petroleum ether (1:1) directly. The extract was dried
      by N2 stream. The residue was dissolved in methanol and separated on a micro
      Bondapak C18 (Waters) column 150 mm x 3.9 mm i.d.,
      acetonitrile:dichloromethane:methanol (85:10:5) as mobile phase. It was then
      detected at 450 nm by UV/VIS spectrophotometer. The retention times of alpha
      carotene, beta-carotene, gamma-carotene, lycopene and canthaxanthin by
      simultaneous determination were 15.25, 16.12, 12.87, 10.38 and 5.37 min,
      respectively. Detection limits were 0.25, 0.22, 0.18, 0.14 and 0.05 mg/L.
      Recoveries were 92.38%, 94.33%, 92.40%, 93.21% and 96.40%, respectively. The
      coefficients of variation were 2.6%, 3.5%, 2.8%, 2.8% and 3.3%, respectively. The
      method was simple, rapid and accurate.

PMID- 15739344
TI  - [Determination of beta-carotene in Fructus lycii by nonaqueous reversed-phase
      high performance liquid chromatography].
AB  - A simple, rapid and accurate quantitative method was established for the
      determination of beta-carotene in Fructus lycii by isocratic nonaqueous RP-HPLC.
      Separation was obtained by using Shim-Pack CLC-ODS column (6 mm i.d. x 150 mm, 5
      microm) and mobile phase of methanol/ethyl acetate (50:55, V/V) with flow rate of
      1 mL/min. The eluates were monitored with UV/VIS detector at 448 nm. The
      retention time for beta-carotene was 7.33 min. The calibration curve was linear
      in the range of 1.0-5.0 mg/L with r=0.9998. The average recovery for beta
      carotene was 97.1% with a coefficient of variation of 1.9%. The content of beta
      carotene in Fructus lycii from different areas was also determined.

PMID- 15739345
TI  - [Separation and determination of metsulfuron, bensulfuron, acetochlor by high
      performance liquid chromatography].
AB  - In this paper a high performance liquid chromatographic method for the separation
      and determination of metsulfuron, bensulfuron and acetochlor in the composite
      herbicide "Nongjiayi" is described. The concentration of methanol in the mobile
      phase and the temperature of the column affected the k' factor and the separation
      of the three active ingredients. Impurities in the "Nongjiayi" did not interfere
      with the determination. Chromatographic conditions were Shim-Pack CLC-C8 (150 mm
      x 6 mm i.d., 5 microm), mobile phase of methanol-water (60:40, V/V) and UV
      detector at 240 nm. Quantification was carried out with the three external
      standards. The average recovery was 98.81% with RSD=0.80% for metsulfuron, 99.10%
      with RSD=0.78% for bensulfuron and 99.72% with RSD=0.69% for acetochlor. The
      linear range of this method was 0.10-0.40 microg (r=0.9994) for metsulfuron, 0.40
      1.60 microg (r=0.9995) for bensulfuron and 10-40 microg (r=0.9987) for
      acetochlor. The method is accurate, rapid and reproducible and can be applied to
      quality control for the "Nongjiayi".

PMID- 15739346
TI  - [Rapid determination of aspartame in compound sweetening by reversed-phase high
      performance liquid chromatography].
AB  - A method for rapid determination of Aspartame in compound sweetening by reversed
      phase high performance liquid chromatography is presented. Aspartame in compound
      sweetening was separated in a short column (Ultrasphere XL-ODS, 3 microm, 4.6 mm
      x 70 mm) by using CH3OH-0.02 mol/L NH4Ac as mobile phase. The flow rate was 0.8
      mL/min. Detection was performed with UV detector at 220 nm. The injection volume
      was 20 microL. It was qualitatively analysed by UV scanning at a wavelength range
      of 200-350 nm under no-stop flow according to their retention time. Quantitative
      analysis was carried out by measuring peak height and comparing it with external
      standard. The minimum detectable amount was 5 microg/L. The linear range of the
      calibration curve was 40-200 mg/L. The average recovery of Aspartame was 92%. The
      relative standard deviation was 2.9%. This method is simple, rapid and sensitive.

PMID- 15739347
TI  - [Determination of solanesol in the extracts of tobacco leaves by high performance
      liquid chromatography (HPLC)].
AB  - Solanesol, a terpene compound mainly isolated from tobacco, is an important
      intermediate of medicines such as vitamin K2 and coenzyme Q10. This paper
      presents an HPLC method for the determination of solanesol in the extracts of
      tobacco leaves. Solanesol is separated completely on a Zorbax-SIL column, 250 mm
      x 4.6 mm i.d., by using a mixture of n-hexane, isopropyl ether and ethyl acetate
      (6:3:1) as mobile phase and determined refractometrically. The isopropyl ether
      makes the chromatographic peak sharp and the addition of ethyl acetate can
      prevent the column from blockade during the analysis, and the appropriate
      temperature (30 degrees C) is beneficial to the shortening of analysis time. This
      method is fast, accurate and reproducible. It has good linear relationship in the
      range of 0.2-4 microg. The results have shown that the average recovery is 96.4%
      and coefficient of variation is 2.8%.

PMID- 15739348
TI  - [Determination of sulpride in human plasma by high performance liquid
      chromatography].
AB  - This paper describes a reliable method for the pharmacokinetic study of Sulpride
      in human plasma by reversed-phase high performance liquid chromatography. To
      compensate the loss of Sulpride during the extraction procedure we used an
      internal standard very similar in chemical structure and UV absorbance to those
      of Sulpride. The mobile phase was methanol-water-acetic acid (60:30:1) with a
      flow rate of 1.2 mL/min. A UV detector was used at 290 nm. The linear range was 5
      100 mg/L and the detectable limit was 1.0 mg/L. The recovery and RSD were 97.95%
      99.96% and 2.6%-5.1% respectively. The results showed that this method is a
      sensitive and accurate one which makes the pharmacokinetic study of Sulpride
      possible. If the concentration was too low to be detected by UV monitor, a
      fluorescence detector could be used with the excitation wavelength at 299 nm and
      emission at 342 nm. We analyzed the plasma samples from 30 day-treated psychotic
      patients and got the satisfactory results.

PMID- 15739349
TI  - [Determination of amino acid contents in cotton-seed-cake powder].
AB  - In this work, the contents of amino acids in three kinds of cotton-seed-cake
      powder from domestic and abroad were determined by using Waters Automatic Amino
      Acid Analyzer with post-column derivatization and fluorescence detection. The
      operating conditions were cation exchange resin column, 250 mm x 4.6 mm i.d.,
      gradient elution, detection wavelength lambda(ex) = 338 nm and lambda(em) = 425
      nm. The results showed that contents of amino acids from both domestic cotton
      seed cakes were less than those from abroad.

PMID- 15739350
TI  - [Determination of thiodicarb by reversed-phase high performance liquid
      chromatography].
AB  - In this paper, a method for determination of thiodicarb by reversed-phase high
      performance liquid chromatography (RP-HPLC) is presented. Analysis was performed
      on a 250 mm x 4.6 mm i.d. octadecylsilica (ODS or C18) bonded phase column in 8
      minutes. Methanol/water mobile phase was used. Ultraviolet detector was used for
      detection at 232 nm wavelength. The internal standard method (using dimethyl
      phthalate as the internal standard) was employed. The linearity of the method was
      verified. The relative standard deviation (RSD) of determination for 75%
      thiodicarb wetted-powder was 0.18%. The average recovery was 99.89%. The method
      has been used for analysis of pesticide products and control of production.

PMID- 15739351
TI  - [A further study on the correlation between molar response value and molecular
      connectivity indices].
AB  - It has been shown that there exists very good correlation between molar response
      values and corresponding molecular connectivity indices for alkane, benzene
      series and alkanol on both TCD and FID and for ketone on TCD. The results of
      multivariate linear regression are as follows. Molar response values (SM) on TCD:
      alkanes SM = 32.55 + 32.71 1X + 1.20 2X - 7.33 3X, r = 0.9951, S = 1.6313, N = 32
      (1) benzene series SM = 30.00 + 20.30 1Xv + 13.32 2X, r = 0.9880, S = 2.7689, N =
      13 (3) alkanols SM =42.22 + 23.71 1Xv + 4.52 2X, r = 0.9914, S = 3.9610, N = 17
      (5) ketones SM = 55.10 + 21.46 1Xv + 4.82 2Xv, r = 0.9914, S = 3.1361, N = 11 (7)
      Molar response values (SM) on FID: alkanes SM = 14.58 + 23.76 1X + 7.77 2X + 2.52
      3X, r = 0.9967, S = 2.1762, N = 50 (2) benzene series SM = 39.45 + 22.25 1Xv +
      6.63 2X, r = 0.9880, S = 2.4137, N = 20 (4) alkanols SM = -5.31 + 25.48 1Xv +
      8.92 2Xv r = 0.9930, S = 4.8979, N = 14 (6) where r and S are regression
      coefficient and residual standard deviation, respectively; N is the data number;
      1X, 2X and 3X are the first, second and third order molecular connectivity
      indices, respectively. 1Xv and 2Xv are the first and second order molecular
      connectivity indices for which the oxygen atom and the degree of unsaturation has
      been revised, respectively.

PMID- 15739352
TI  - [Microbore liquid chromatography with dual electrode electrochemical detection of
      monoamine transmitters in brain microdialysates].
AB  - In the present work, the method of microbore liquid chromatography(MLC) with dual
      electrode electrochemical detection (DEED) was used to determine the monoamine
      transmitters and their metabolites in the striatal microdialysates from the
      anaesthetized rats. The potentials applied on the upstream (anodic) electrode and
      downstream (cathodic) electrode were set at +0.72V and +0.05V versus an Ag/AgCl
      reference electrode respectively. The interference of the large early-eluting
      peaks from brain dialysate was well eliminated on cathodic detection on the basis
      of electrochemical reversibility of catechol compounds. The collection efficiency
      of catecholamine (NA, A and DA) and DOPAC, that is the ratio of their responses
      in downstream electrode to those in upstream, was found to be in the range of
      0.690 to 0.768, thereby providing reliable identification and measurement of
      early elutes. MLC-DEED is one of the best methods for the determination of
      monoamine transmitters at trace level. To optimize separation and detection,
      these adaptations were made to the system with respect to the injection valve,
      flow rate of the pump, connections between injector, column and detector, and
      cell volume of the detector. The detection limit could reach 1pg or less per
      injection, and the amounts, at least in the range of 2-200pg, were linearly
      correlated with the peak areas both at anodic detection and at cathodic
      detection. Prior to the collection of samples the probe recovery was measured in
      vitro at room temperature, and the recovery (%) for NA, DA, DOPAC, 5-HIAA, 5-HT
      and HVA were 19.5, 18.9, 22.1, 14,6, 16.5 and 19.3 respectively. The reported
      concentration of each compound was corrected according to probe recovery. The
      basal concentration of DA and 5-HT in striatal microdialysates was 12.5 +/- 1.8
      and 5.0 +/- 0.7nmol/L. The perfussion of high K+ (100 mmol/L) through the
      dialysis probe induced a large increase of the concentration of NA, DA and 5-HT
      in microdialysates, and further increase of the concentration was observed in rat
      postmortem. The critical points for MLC-DEED are briefly discussed.

PMID- 15739353
TI  - [Preparation and evaluation of stationary phase of high performance liquid
      chromatography for the separation of basic solutes].
AB  - A bonded phase for high performance liquid chromatography (HPLC) has been
      prepared by the new reaction between silica and silicon ether. The ether was
      synthesized from alkylchlorosilane and pentane-2,4-dione in the presence of
      imidazole under inert conditions by using anhydrous tetrahydrofuran as solvent.
      The bonded phase thus obtained was characterized by elemental analysis, diffuse
      reflectance infrared Fourier transform (DRIFT) spectroscopy and HPLC evaluation.
      The carbon content was 9.4% and the surface coverage almost attained
      3.0micromol/m2 without end-capping. The silanol absorption peaks of the product
      cannot be observed from the DRIFT spectrum, which revealed that the silanization
      reaction proceeded thoroughly. The basic solutes, such as aniline, o-toluidine, p
      toluidine, N,N-dimethylaniline and pyridine were used as the probe solutes to
      examine their interaction with the residual silanols on the surface of the
      products. No buffer or salt was used in the mobile phase for these experiments.
      In comparison with an acidic solute, such as, phenol, basic aniline eluted in
      front of phenol, and the ratio of asymmetry of aniline peak to that of the phenol
      peak was 1.1. Furthermore the relative k' value of p-toluidine to that of o
      toluidine was also 1.1. All the results showed that the stationary phase has
      better quality and reproducibility and can be used for the separation of basic
      solutes efficiently.

PMID- 15739354
TI  - [Deviation of size-exclusion chromatographic behavior of tryptophan on TOYOPEARL
      HW-40S column].
AB  - A deviation of size-exclusion chromatographic behavior of amino acids on
      TOYOPEARL HW-40S column is reported. On the column 18 amino acids were not eluted
      in the same fraction in the total volume, but separated into 5 fractions with
      tryptophan as the last one far behind the total volume. Interaction between
      tryptophan and the matrices was investigated under different conditions in order
      to elucidate the chemical nature of the deviation. It was found that addition of
      trifluoroacetic acid and sodium chloride of high concentration in mobile phase,
      dramatically increased the retention time of trypophan, while addition of
      acetonitrile, sodium chloride of lower concentration and the hydrogen bond
      breaker urea reduced the interaction. It is concluded that adsorption of
      tryptophan on TOYOPEARL HW-40S is basically due to the hydrophobic nature with
      limited influence of hydrogen bond and ionic interaction. The former factor can
      be eliminated by keeping acentonitrile concentration over 50% (V/V), while the
      latter two can be reduced to the minimum by adding 0.17mol/L sodium chloride and
      3.51mol/L urea. The results not only lead to better understanding of size
      exclusion chromatography of this matrices, but also help to apply hydrophobic
      chromatography of this matrices to the isolation of amino acids and peptides.

PMID- 15739355
TI  - [Research on the variation of peak shape in capillary zone electrophoresis].
AB  - The influence of operation conditions, such as, injection time, applied voltage
      and effective length of capillary column, on parameters of peak shape in
      capillary zone electrophoresis (CZE) was investigated by using exponential
      modified Gaussian (EMG) equation. The CE experiments were carried out by using
      the sample of derivatives of benzoic acid and small peptides. The experimens
      indicated that there was a significant effect of injection time on W1/2 and that
      the peaks changed from tailing to leading when the injection time was over 3
      seconds in the case of pressure injection. It is recommended that an injection
      time less than 3 seconds can lead to a good column efficiency. The good linear
      relationships between tm and tau, sigma, W1/2 (t) with different separation
      voltages were observed. In the range of experimental conditions (11-27kV), higher
      voltage could lead to smaller zone dispersion, giving rapid and high efficient
      separation, and the voltage was insignificant on peak tailing. It was also shown
      that sigma, tau and W1/2 increased slightly with increasing the effective length
      of capillary column.

PMID- 15739356
TI  - [Research on the reproducibility and selection of experimental conditions of
      capillary electrochromatography].
AB  - In this work, we prepared the packed columns for capillary electrochromatography
      (CEC) with 75microm and 100microm i.d., both of coupled mode and uncoupled mode.
      A mixture of thiourea and other three aromatic compounds was employed to evaluate
      the efficiency of the CEC columns. RSD values of retention times smaller than
      2.12% was obtained on the home-made CEC system. The influence of pH value and the
      concentration of the organic solvent in the buffer on the retention behavior was
      investigated, giving a guide to the selection of experimental conditions. High
      speed analysis can be achieved by using high pH value buffers. Higher
      concentration of acetonitrile will improve the elution ability, while lower
      ocncentration of acetonitrile would improve the resolution. Seven kinds of
      neutral molecules were separated efficiently within 25 minutes. The results from
      the two modes of CEC columns were compared.

PMID- 15739357
TI  - A new calixcrown polysiloxane stationary phase for capillary gas chromatography.
AB  - A new calixcrown polysiloxane gas stationary phase (M-C[4]C-5PSO) in which
      calixcrown monomers lie in the main chain of polysiloxane was first synthesized.
      The calixcrown polysiloxane exhibits high thermostability and good separation
      abilities for nitro, chloro- and methyl substituted benzene or phenol isomers.
      The application of M-C[4]C-5PSO and the separation mechanism will be further
      studied.

PMID- 15739358
TI  - [Brush-type chiral stationary phase for chiral resolution in high performance
      liquid chromatography].
AB  - A review is presented about brush-type chiral stationary phase in high
      performance liquid chromatography chiral resolution, dealing with design,
      synthesis and applications, of various brush-type chiral stationary phases (CSP).
      The advances of study of chiral recognition mechanism are introduced and the
      development trends of the brush-type chiral stationary phase in the future
      proposed. Eighty-four references are cited in this paper.

PMID- 15739359
TI  - [High performance liquid chromatographic analysis of organic acids in foods].
AB  - Because of the speed, selectivity, reliability, and simple sample preparation
      high performance liquid chromatography (HPLC) is the preferred method for
      simultaneous separation and determination of organic acids in foods. Ion exchange
      chromatography, ion exclusion chromtography and reversed phase HPLC are the most
      common chromatographic modes for analysis of organic acids in foods. The
      development and application of the three chromatographic modes are reviewed with
      54 references. Ion exchange chromatography is most satisfactory for analysis of
      organic acids in foods, because organic acids are not interfered by other organic
      compounds, and inorganic anions in foods are determined simultaneously with
      organic acids.

PMID- 15739360
TI  - [Application of gas chromatography to identification of Clostridium difficile].
AB  - With chromatograph produced in our country, the gas chromatograms of fatty acid
      metabolites of five strains of Clostridium difficile isolated from stool of
      patients with tumor and one strain for control were compared and analysed by
      using stainless steel chromatographic column, 15% modified polyethylene glycol
      stationary phase nitrogen carriergas 140 degrees C column temperature and 190
      degrees C detector temperature. The chromatograms of the isolated strains and the
      control strain were found to be extremely similar. All of them were peaks of
      acetic, propionic, isobutyric, butyric, isovaleric, valeric, and isocaproic acid.
      In comparison, the peaks of acetic, butyric, and isocaproic acid were higher,
      those of the isobutyric and isovaleric acid were medium and those of propionic
      and valeric acid were lower. Moreover, a low, flat peak appeared at 14th minute
      and was similar to that of p-cresol reported by Berg et al. The results of our
      experiment revealed that gas chromatography may be used as a simple, quick method
      for the identification of Clostridium difficile.

PMID- 15739361
TI  - [Identification of volatile compounds of hawthorn by gas chromatography/mass
      spectrometry (GC/MS)].
AB  - The volatile compounds of three cultivars of hawthorn were studied. Changko
      (Crataegus pinnatifida Bge.) hawthorn fruit was harvested after ripening from
      Hubei Province and those of Heihong and Dajinxing were from Shandong Province.
      The volatile compounds of each hawthorn cultivars were obtained by SDE
      (simultaneous distillation-extraction) equipment, by using CH2Cl2 as extracting
      solvent. The volatile extract was concentrated at 40-50 degrees C under vacuum to
      0. 05mL or so and was ready for GC and GC/MS analysis. A DB-Wax fused silica
      capillary column (50m x 0.32mm i.d.; 1microm thickness) and a flame ionization
      detector (FID) was employed in GC analysis. The temperature program included of a
      5 min isothermal period at 40 degrees C, temperature increases of 2 degrees C/min
      from 40 degrees C to 240 degrees C, and a 60 min isothermal period at 240 degrees
      C. Mass spectra were obtained by electron impact at 70eV and a source temperature
      of 250 degrees C. Thirty-two volatile compounds of the hawthorn fruit were
      identified, which comprised 61%-68% of the volatile fraction. The ten major
      components were cis-3-hexenol, cis-3-hexenyl acetate, alpha-terpineol, furfural,
      hexanol, hexyl acetate, nonanal, citral, 3-penten-2-one and trans-2-decenal. The
      molecular weight range of the major volatile fraction covers from C3 to C10. Both
      qualitative and quantitative differences in the volatile constituents among the
      three cultivars were not remarkable.

PMID- 15739362
TI  - [Establishment of a coupling method of high performance liquid chromatography and
      capillary gas chromatography].
AB  - An on-line coupling system of normal phase microbore HPLC and capillary GC has
      been established, in which retention gap technique with on-column injection and
      partially concurrent solvent evaporation with early vapor exit were used. The
      conditions suitable for the coupling system of HPLC and CGC must be determined
      experimentally since the factors have to be adjusted with respect to solvent
      evaporation temperature and column inlet pressure etc. The suitable solvent
      evaporation temprature for the mobile phase used for this system, n-hexane, was
      about 70 degrees C. A temperature much, lower or higher than 70 degrees C will
      influence the GC analysis. In addition, solvent evaporation temperature and
      column inlet pressure are interacting, that is, higher solvent evaporation
      temperature needs higher inlet pressure. At the above evaporation temperature,
      the suitable inlet pressure for this system was about 0.2MPa. In order to
      minimize the extra-column effect on the LC peaks, thin transfer-line and
      connectors of zero-dead volume between LC column and GC column must be used. The
      separation and analysis of aromatics in a light diesel fuel was performed by
      using this system with 15cm x 2mm i.d. YGW (5microm) silica LC column and 60m x
      0.25mm i.d. OV-101 GC column under the above conditions. The analytical results
      show that the system of on-line coupling of HPLC with CGC is a reliable
      analytical tool for microcomponents in complex mixtures, especially for those
      requiring sample preparation prior to GC.

PMID- 15739364
TI  - [Determination of metronidazole in gastric juice by high performance liquid
      chromatography].
AB  - Metronidazole (MTZ) is the first chosen drug of anti-anaerobe which was
      recommended by World Health Organization. In this paper a high performance liquid
      chromatographic (HPLC) method has been developed to determine the concertration
      of MTZ in human gastric juice. Gastric juice was obtained by intubation after
      taking drug, then the sample was precipitated with ethanol to remove proteins,
      centrifuged, filtered and finally assayed by HPLC. The operating conditions were
      reversed phase C18 column (4mm x 150mm), CH3OH:KH2PO4 (5mmol/L, pH 4.0) = 10:90
      mobile phase with flow rate of 1.5mL/min and detection wavelength at 320nm. The
      standard working curve was Y = -1.63 + 1.15X, with r = 0.9999, n = 7. The linear
      range was 2.5-200mg/L. The detection limit was 0.4mg/L. The average recovery was
      96.0% and the coefficient of variation was 3.07%. This method can be applied to
      guide clinical therapy and pharmaceutical research.

PMID- 15739363
TI  - [Scale-up preparation of hydrophobic interaction chromatographic packing
      materials based on inorganic matrix].
AB  - Based on inorganic matrix controlled pore glass (CPG) and macro-pore silica
      sphere, by using polyethylene glycol (PEG 1000) as a ligand, a preparation method
      of hydrophobic interaction chromatographic (HIC) packing material was improved by
      adding a proper catalyst during the bonding process. The packing material can be
      synthesized in a scale-up batch, for example 150g for each batch, both for
      analytical and preparative columns. The retention of proteins, such as cytochrome
      C (Cyt-C), chymotrypsingen-A (Chy-A), lysozyme (Lys) and ribonuclease(Rnase), is
      increased with the increasing of (NH4)2SO4 concentration in the eluant 2.5 mol/L
      of salt concentration for the mobile phase was chosen by considering the
      separation efficiency and equipment life. After comparing the effect of pH for
      the retention of proteins it is found that the proteins are well separated at pH
      7. The time of linear gradient elution program was optimized in considering the
      separation efficiency and speed. It is better to take 30 minutes of the gradient
      program for the separation. Six standard proteins can be well separated with the
      high-performance HIC column in the linear gradient elution program from 2.5 to 0
      mol/L of (NH4)2SO4 in 50 mmol/L of phosphate buffer solution within 30 minutes.
      Cyt-C, Rnase, Lys and Chy-A can be separated by the HIC column based on CPG
      matrix. Six proteins, Cyt-C, Rnase, Lys, Chy-A, insulin(Ins) and lipase (Lip) can
      be well separated on the column based on silica matrix with gradient elution
      program. The recovery of trypsin detected with BAEE method is over 95% after
      purification with the HIC column.

PMID- 15739365
TI  - [Determination of prostaglandin F2alpha release in the rat spinal cord upon
      hydroxyl free radical damage by high performance liquid chromatography].
AB  - As prostaglandin F2alpha is present in biological materials, and plays an
      important physiological role at trace level in the living body, then, highly
      sensitive determination of PGs is required. Various fluorescence derivatization
      reagents have been proposed for the determination of PGs. The 3-bromomethyl-6,7
      methylenedioxyl-1-methyl-2(1H)-quinoxalinone was found to be a highly sensitive
      fluorescence derivatization reagent for PGF2alpha in HPLC with a detectable limit
      of 10-15 fmol for PGF2alpha. In this work we optimized its reaction conditions.
      Thus the PGF2alpha was extracted from the microdialysates with ethyl acetate at
      pH 3.0-3.5 following which the extracts were evaporated to dryness. The residue
      was derivatized by adding acetonitrile, KHCO3, Br-DMEQ and 18-crown-6-ether at 50
      degrees C for 30min in the dark. The corresponding fluorescent derivatives
      produced were separated on a C8 column (Phase-Sep Ltd.), 5microm, 4.6mm x 150mm.
      Stepwise elution with different ratios of A and B was carried out. 30:10:60 of
      CHsCN:CH3OH:H2O constituted A solution and 35:30:35 made B solution. The A/B
      (97/3) was first run for 25 min and A/B (50/50) for the next 15min. Then the
      column was equilibrated with A/B (97/3) for 20min before the next sample
      injected. Fluorescence detector was used at lambdaEX 370nm and lambdaEM 455nm,
      and flow-rate of 2.0mL/min. Because the most evidence for a role of free radicals
      in tissue damage is indirect, we attempt to determine whether OH causes release
      of arachidonic acid products in vivo. We did this by (1) generating OH radical in
      vivo in rat spinal cord by administering H2O2 and FeCl2/EDTA through two parallel
      microdialysis fibers so they mixed in the cord, and (2) analyzing PGF2alpha in
      microdialysates in response to OH generation by HPLC. We utilized dialysis fibers
      of < or = 220microm external diameter including their coating except for a 2mm
      dialysis zone which was coated with a thin layer of silicon rubber. When the
      animal was clamped, two microdialysis fibers glued together were inserted through
      the cord until the dialysis zone just placed in the gray matters of the cord. The
      time course of changes in levels of PGF2alpha during OH generation by Fe/H2O2 is
      given. Typical chromatogram of the dialysate collected from one animal is
      illustrated. Prostaglandin F2alpha dramatically increased in response to hydroxyl
      radical generation from undetectable (basal level) to about 333 +/- 166nmol/L
      (SD, n = 5) in 90min, Prostaglandin F2alpha was undetectable when either H2O2 or
      FeCl2/EDTA was administered alone in control experiments, demonstrating that its
      formation was caused by generated hydroxyl radical.

PMID- 15739366
TI  - [Detection of desmosine in elastin by high performance liquid chromatography
      (HPLC)].
AB  - An assay of desmosine (DES) in elastin hydrolysate was performed by HPLC.
      Desmosine alone or its mixture with tyrosine and phenylalanine as well as elastin
      hydrolysate was separated on a C18 column eluted with a mobile phase of MeOH:H2O
      (2:8, V/V) and detected at UV-280nm. The results showed that the time of DES
      eluted in all cases mentioned above was comparable. The ratio of peak area (CA)
      and peak height (CH) between DES and Tyr is 1.4% and 3.4% resectively. It could
      be as a reliable measure to evaluate the quantity of DES in elastin. The
      correlation coefficient r was 0.9956 in the range of 0.16-0.64mg/L for a
      calibration curve of DES concentration vs peak area. In conclusion, this method
      could be used as a biochemical indication to detect the degradation level of
      elastin in the pathological state.

PMID- 15739367
TI  - [Determination of gamma-aminobutyric acid and glutamic acid in human
      cerebrospinal fluid by high performance liquid chromatography].
AB  - Gamma-aminobutyric acid (Gaba) and glutamic acid (Glu) are believed to be the
      major neurotransmitter. Levels in cerebrospinal fluid (CSF) may reflect their
      metabolism in various neurotic and psychiatric diseases. Measurements of Gaba and
      Glu in body fluids will help to elucidate their metabolic role and diagnostic
      value. In the present work, the concentrations of glutamic acid and gamma
      aminobutyric acid in human cerebrospinal fluid were determined by reversed-phase
      high performance liquid chromatography using pre-column derivatized with dansyl
      chloride and UV detection at 254 nm. The mobile phase was A:CH3OH and B:
      THF/CH3OH/0.05 mol/L NaAc (pH 6.2) (5/75/420, V/V) with gradient elution. The
      flow rate was 1 mL/min. CSF samples were deproteinizated with methanol. After
      centrifugation at 15000 r/min for 10 min, the supernatant was introduced into a
      screw-capped vial and evaporated to near dryness at 80 degrees C. Derivatization
      was carried out by the addition of 250 microL of bicarbonate solution (pH 9.8)
      and 250 microL of dansyl chloride solution (4 g/L) followed by heating at 40
      degrees C water bath for 30 min. Extraction was performed with 300 microL of
      ethyl acetate and the organic layer separated was dried at room temperature under
      nitrogen. The dry residue was dissolved and injected into the HPLC system. The
      linear range of the method was 5-1000 micromol/L (r = 0.9988) for Glu and 1-600
      micromol/L (r = 0.9984) for Gaba. The lower limit of detection were 0.002
      micromol/L and 0.001 micromol/L respectively. The recoveries were 96.9%-98.8% and
      97.5%-98.8% and the coefficients of variation of peak height measurements were
      2.2%-3.4% and 3.8%-5.6% respectivery. The method enables a simple, rapid and
      reproducible quantification of Glu and Gaba neurotransmitter.

PMID- 15739369
TI  - [Study on ion chromatography (IC) for the low-molecular weight amines].
AB  - In this paper the retention behaviors of low-molecular weight amines
      (methylamine, dimethylamine, trimethylamine, ethylamine, propylamine sec
      butylamine, n-butylamine, ethanolamine, diethanolamine, triethanolamine) on
      Ionpac CS12 column were for the first time studied with modern ion chromatograph.
      The column is usually used for routine analysis of inorganic cations and it
      strongly retains these organic amines. So they are difficult to be eluted by
      dilute aqueous HCl alone. The addition of acetonitrile (ACN) as a modifier can
      improve the peak shape and resolution. Influences of concentrations (ACN & HCl)
      on separation and detection were investigated separately and the chromatographic
      conditions were optimized. Aqueous solution of 20 mmol/L HCl containing 1% or 5%
      ACN (5% for higher molecular weight amines) was used as the eluant with a flow
      rate of 1.0 mL/min to optimize the column efficiency. In addition to methylamine,
      ethanolamine and diethanolamine, all other amines can well be separated from each
      other. According to the structure they may be divided into three classes: (a)
      methylamine, dimethylamine and trimethylamine; (b) diethanolamine and
      triethanolamine; (c) ethylamine, propylamine, sec-butylamine and n-butylamine.
      The three classes of mixtures were separately injected into the IC system and
      resolutions being obtained by the developed method were: (a) 1.25 and 1.52; (b)
      1.20; (c) 2.45, 2.05 and 2.10 respectively. The new method is characterized by
      rapidity, convenience, sensitivity and simultaneous determination of some
      inorganic cations. It was separately used for determination of diethanolamine,
      triethanolamine, NH4+ in explosive samples and of Na+, K+, MgZ+, Ca2+ in water
      supply with satisfactory results. The retention mechanism of amines on CS12
      column and effect of organic modifier were also preliminarily explored.

PMID- 15739370
TI  - [Determination of chlorosilanes by gas chromatography].
AB  - Chlorosilanes are the essential raw material of SiC fibre made by "CVD (chemical
      vapour deposition)" method. The purity of chlorosilane affects the quality of SiC
      fibre obtained. Therefore, a simple and reliable method for the determination of
      the constituent of chlorosilane is needed. A gas chromatographic method for
      quantitative analysis of chlorosilane is described in this paper. The gas
      chromatographic conditions were as follows: column, 10% diethyl phthalate on 6201
      support (60-80 mesh), 3m x 5mm i.d. stainless-steel column; column temp., 60
      degrees C; injection temp., 110 degrees C; thermal conductivity detector temp.,
      140 degrees C carrier gas H2 with flow rate of 60 mL/min. The results show that
      the method is simple and rapid, and has good precision and reproducibility. The
      coefficient of variation of the method was less than 1% (n = 6).

PMID- 15739368
TI  - [Study on the analysis of organogermanium compounds by ion chromatography].
AB  - A new high performance ion exchange chromatographic method for separation and
      determination of three organogermanium compounds beta-carboxyethylgermanium
      sesquioxide (I), beta-(alpha-methyl) carboxyethylgermanium sesquioxide (II) and
      di-(beta-carboxyethyl) germanium hydroxide (III) has been developed. A Dionex DX
      300 Ion Chromatograph equipped with a Dionex PED-II pulsed electrochemical
      detector (conductivity mode), a Dionex AMMS-1 anion micromembrane suppressor, and
      a Dionex ACI advanced computer interface coupled with AI-450 chromatographic
      software was employed. The separation was achieved by using a Dionex IonPac AS4A
      SC column as analytical column, sodium tetraborate solution as eluent, and
      sulfuric acid solution as regenerant. For reducing run time, a gradient program
      was chosen. The detection limits (S/N = 3, expressed as germanium) for the three
      compounds were 0.038mg/L (I), 0.035mg/L (II) and 0.025mg/L (III), respectively.
      The method has been applied to the analysis of two tonic oral drinks, and the
      average recoveries for the three compounds ranged from 95%-101%. The results
      obtained were in agreement with those of hydride generation atomic fluorescence
      spectrometry (HG-AFS).

PMID- 15739371
TI  - [Determination of dimethyl ether correction factors in gas chromatography with
      TCD and FID].
AB  - Dimethyl ether (DME) correction factors in gas chromatography with thermal
      conductivity detector (TCD) and flame ionization detector (FID) by using H2 as
      carrier gas were determined in this work. The homemade DME gas was quantitatively
      absorbed in ice-cold water. With ethanol as standard, the aqueous mixture was
      injected into a gas chromatograph, equipped with serially-connected TCD and FID.
      The weight correction factors of DME based on methanol were 0.86 and 0.55 for TCD
      and FID respectively. The result for TCD was also confirmed by calculation based
      on the stoichiometrical transformation of methanol into DME in reaction gas
      chromatography.

PMID- 15739372
TI  - [Analysis of ethers and related olefines in light gasoline from catalytic
      cracking after etherification by gas chromatography/mass spectrometry (GC/MS)].
AB  - A method for qualitative and quantitative analysis by GC/MS and GC of ethers and
      related olefines in light gasoline from catalytic cracking before and after
      etherification has been presented. By means of the analysis of the reactive
      olefines and the ethers produced it is concluded that six kinds of olefines had
      taken part in the etherification process, they were, 2-methyl propene-1,2-methyl
      butene-2,2-methyl butene-1,2-methyl pentene-1,2-ethyl butene-1, and 2-methyl
      pentene-2, and the four ethers produced were 2-methoxy-2-methyl propane, 2
      methoxy-2-methyl butane, 2-methoxy-2-methyl pentane and 3-methoxy-3-methyl
      pentane. These ethers are all contributing to enhance the octane number.

PMID- 15739373
TI  - [Quantitative analysis of phoxim and cypermethrin using wide bore capillary
      column gas chromatography].
AB  - A compound pesticide, 20% P-C emulsion, consisting of 18.5% phoxim and 1.5%
      cypermethrin pesticides and other accessory agents is especially effective in
      controlling and killing boll worms. For its quality control some difficulties
      were encountered. In this paper we propose a simple and practical method for GC
      analysis of the product by use of a short wide bore capillary column (HP-1, 5m x
      0.53mm x 2.65microm), high carrier gas flow rate and high-speed temperature
      programming etc.. Content analysis of efficient composition of "20% P-C emulsion"
      was completed under the chromatographic conditions using methyl parathion as an
      internal standard. Coefficient of variation of phoxim and cypermethrin were 0.67%
      and 1.0% respectively.

PMID- 15739375
TI  - [Liquid chromatographic separation of pepsinogens].
AB  - In this work, we reported a method for the purification of pepsinogens from human
      gastric mucosa with high pressure gel filtration chromatography (HPLC) and medium
      pressure anion exchange chromatography (MPLC). First, the two fractions of Pg1
      and mixture of PGI and PGII were separated from pepsinogens with HPLC on a Bio
      Sil SEC-125 column within 50min. Then the mixture of fractions of PGI and PGII
      was further separated with MPLC on a Bio-Scale Q2 column within 30min.

PMID- 15739376
TI  - [Determination of docosyl ferulate in extract of Pygeum africanton Hook. by high
      performance liquid chromatography (HPLC)].
AB  - This paper reports a method for the determination of docosyl ferulate in the
      extract of bark of pygeum africanum Hook. by HPLC. After the sample was
      pretreated, the docosyl ferulate was well separated and determined on a
      Spherisorb C18 column (250 x 4.6mm, 5microm) using a mobile phase of methanol
      with a flow rate of 1mL/min. The column temperature was selected at 40 degrees C
      to avoid tailing of peak. UV detection was performed at 326nm. In order to
      confirm the docosyl ferulate separated from sample, the peak apex at 10.4 minute
      was scanned from 195nm to 360nm by photodiode array detector. Its spectrum showed
      the maxium absorption peak at 240nm and 326nm corresponding with the spectrum of
      docosyl ferulate. The linear correlation was observed from the 10mg/L to 100mg/L
      of docosyl ferulate (r = 0.9995). The average recovery was 98.4% +/- 1.98%. Three
      batches of sample were determined.

PMID- 15739374
TI  - [Reversed-phase high performance liquid chromatographic (RP-HPLC) analysis of
      taxol and related taxanes extracted from Taxus wallichiana zucc].
AB  - A method for determination of taxol, 10-deacetyl-7-epitaxol, cephalomannine, 10
      deacetyl taxol, baccatin III and 10-deacetylbaccatin III, is reported and their
      retention mechanism is also discussed. These compounds were separated well by RP
      HPLC on a Resolvepak C18 column with methanol-water-phosphoric acid (60:40:0.5)
      as mobile phase and UV detector at 228nm. The powdered stems were extracted with
      95% ethanol, refluxed for 8 hrs and filtered and then the residue was partitioned
      three times between water and chloroform. The organic phase was evaporated to
      dryness and the residue dissolved in reagent methanol and was submitted to HPLC
      analysis. The results showed that there is a linear relationship between the peak
      area and the amount of these compounds over the range of 0.1-2.0microg. The
      lowest detectable concentration of these compounds was below 0.1microg.

PMID- 15739377
TI  - [The simultaneous analysis of substance P, somatostatin, neurokinin and
      neurotensin by capillary zone electrophoresis].
AB  - Neuropeptides play an important part in several different areas of
      neurochemistry. Recently, capillary electrophoresis (CE) was developed for
      analysis of neuropeptides. This paper reports a capillary zone electrophoretic
      method for the simultaneous separation and quantitative determination of the
      substance P (SP), somatostatin (SS), neurokinin (NKA) and neurotensin (NT). The
      separation was performed on a 50microm x 60cm fused-silica capillary using
      0.1mol/L at pH 2.7 phosphate as buffer. The eluted fractions were detected at
      214nm.

PMID- 15739379
TI  - [An analysis of maicaodi by high performance liquid chromatography].
AB  - Maicaodi has recently been developed and produced by the pesticide plant of
      Nanjing Agricultural University. The quantitative analysis of the effective
      components--tribenuron methyl and R (-)napropamide in wettable powder of
      Maicaode, by a high performance liquid chromatographic method was carried out
      with a Lichrosorb Si-60 20cm x 0.46cm i.d. column, mobile phase of petroleum
      ether/isopropanol/methanol/acetonitrile/chloroform mixture solvent (80:5:5:5:5)
      and internal standard of diisooctyl phthalate. The sample was detected by
      ultraviolet absorption at 254 nm. The retention times of tribenuron methyl and R
      (-)napropamide were 10-11min and 6-7min respectively. The coefficient of
      variation of this analysis was 0.34% with a recovery of 99.51%-100.32%. The
      coefficient of linear correlation was 0.9999.

PMID- 15739378
TI  - [Optimization of the solvent system in thin-layer chromatography (TLC)].
AB  - Much effort in TLC has been devoted to optimization methods of solvent system in
      order to get best separation of components. Various optimization methods have
      been established, but the universality of some methods was poor. They were only
      applicable to samples of known components. This paper reports a complex method.
      When the complexity of the solvent system was determined, uniform design was used
      to arrange experiments, the data obtained from scanning chromatogram were input
      computer to get regression equation. The precision of the regression equation
      should be judged at first. If the precision was proper, the regression equation
      could be input the program of the complex method to obtain the composition of the
      solvent system. Optimization results were dichloroethane-benzene-methanol
      (4.81:4.42:0.78) for cortical hormone; toluene-ethanol-dichloroethane
      trichloromethane (2.30:1.46:3.32:2.92) for sulfa drugs and trichloromethane
      methanol-ethyl acetate (3.30:3.29:3.41) for ginkgo biloba. Then the verification
      experiment was made. The verifying test showed that the experimental results are
      identical with the calculated ones.

PMID- 15739380
TI  - [Analysis of vitamin K1 in Cephalanoplos segetum (Bunge) Kitam by high
      performance liquid chromatography].
AB  - A modified method for the analysis of vitamin K1 in Cephalanoplos segetum (Bunge)
      Kitam, an edible wild herb, is proposed in this paper. The ground herb sample was
      extracted with CHCl3, followed by evaporation to dryness with nitrogen. The
      residue was dissolved with methanol, filtered through 0.5microm micropore
      membrane and then determined on a Novapak C18, 150mm x 3.9mm i.d., column with
      methanol/isopropanol (70:30) as mobile phase and UV-248nm as detector. Recovery
      was more than 95% with CV 1.23%. The method is simple and accurate without
      saponification, extraction and evaporation procedures as those used previously.

PMID- 15739381
TI  - Consanguinity in two Uruguayan cities: historical evolution and characteristics
      (1800--1994).
AB  - BACKGROUND: Information about consanguinity in Uruguay is scarce and limited to
      the end of the 20th century. AIM: To determine the frequency and characteristics
      of consanguineous marriages, as well as chronological trends, in two Uruguayan
      cities over almost two centuries. SUBJECTS AND METHODS: We analysed 28,393 Roman
      Catholic Church marriage records and Diocesan consanguinity dispensations
      belonging to the cities of Melo (Northeast), and Montevideo (South), for the
      period 1800--1994. RESULTS: 633 (2.23%) marriages were consanguineous. Among
      them, first cousin marriages were the most common (58.8% of all consanguineous
      marriages, including double consanguineous), especially those where the bride and
      groom were related through their maternal side. During the first decades of the
      19th century both regions showed low levels of consanguinity. Consanguinity
      reached its maximum during the mid-1800s and decreased significantly throughout
      the 20th century. The overall mean coefficients of inbreeding were moderate in
      both cases, being greater in the Northeast (alpha=0.00165) than in the South
      (alpha = 0.00089). CONCLUSIONS: The low level of consanguinity as well as the
      structure of consanguineous marriages (distribution by degrees) is similar to
      that found in other southern South American countries. Temporal trends are
      similar to those found in industrialized regions in Europe, with maximum
      inbreeding levels during the middle-late 19th century; however, the clear
      predominance of first cousin unions, differs from most of the data for European
      countries. Small differences between the two cities can be related to diverse
      facts, such as socio-economic conditions, ethnic origin, immigration, and
      sampling.

PMID- 15739382
TI  - Mode of inheritance of finger dermatoglyphic traits among Vaidyas of West Bengal,
      India.
AB  - BACKGROUND: It is well established that dermatoglyphics are genetically
      determined. But, to date, few studies have given attention to the inheritance
      pattern of dermatoglyphics. Furthermore, despite the existence of different
      advanced statistical packages, none of these previous studies implemented a model
      fitting technique to reveal the mode of inheritance. Thus, the genetic nature of
      dermatoglyphics is still not clear. AIM: In the present communication, an attempt
      has been made to provide some information regarding the genetics of finger
      dermatoglyphics by estimating the magnitude and mode of inheritance of these
      traits. SUBJECTS AND METHODS: The fingerprints of 824 individuals from 200
      families including two generations were collected from Barasat in North 24
      Parganas, West Bengal. The study includes familial correlations between first
      degree relatives and corresponding heritabilities. In the final stage,
      segregation analyses by the Pedigree Analysis Package (PAP) were conducted on
      these data to understand the mode of inheritance. RESULTS: The major findings
      indicated the following: (a) Familial correlations in all possible relationships
      (except spouse correlation) were statistically significant and of comparable
      magnitude. (b) The corresponding heritabilities were in the range between 59% for
      Pattern Intensity Index (PII) and 77% for Total Finger Ridge Count (TFRC). These
      estimates were in agreement with previously published data on this subject. (c)
      By segregation analysis, the 'Sporadic', 'Environmental', 'No major gene effect'
      as well as 'No polygenic component' models were strongly rejected (p < 0.05) and
      the hypothesis of a major gene's (MG) influence on all studied traits was
      accepted, though the proportion of MG variance was low. (d) The Most Parsimonious
      Mendelian model clearly indicated the contribution of a major gene with dominant
      (for PII) and additive (for two ridge counts) effects. CONCLUSION: The present
      report supports the evidence of the existence of a major gene on these
      dermatoglyphic traits and the transmission of this effect is consistent with
      Mendelian expectation.

PMID- 15739383
TI  - Genetic variability at the D1S80 minisatellite: predominance of allele 18 among
      some indian populations.
AB  - BACKGROUND: Hypervariable minisatellites are considered as useful genetic markers
      in population studies because they are highly polymorphic, multiallelic and co
      dominant in nature. The D1S80 minisatellite is one of the well studied markers,
      and has been used for differentiating population groups of various geographic,
      linguistic, cultural and genetic origins. OBJECTIVE: The present study reports
      the genetic variation observed at the D1S80 minisatellite among seven
      anthropologically distinct ethnic groups from Kerala state in south India and is
      compared with other reported Indian and world populations. SUBJECTS AND METHODS:
      DNA was isolated from the peripheral blood samples of 282 random, normal and
      healthy volunteers, PCR amplified and electrophoresed on 4% PAGE followed by
      silver staining. RESULTS: A total of 22 alleles (14-39 repeats) were detected
      with high heterozygosity (0.63-0.84) and Polymorphic Information Content (PIC)
      values (0.63-0.83). Allele 18 was the predominant allele, except in Ezhavas. The
      comparison of allele frequency data with world populations including other
      studied Indian ethnic groups has revealed that the majority of Indian populations
      possessed allele 18 as the predominant allele. In contrast, allele 24 was
      reported to be the predominant allele worldwide with a few exceptions.
      CONCLUSIONS: This study at the D1S80 minisatellite on seven ethnic groups will
      provide useful information for the Indian population genetic database. However,
      the most important observation was the predominance of allele 18 among the
      majority of Indian ethnic groups. The reason is not clear yet and thus further
      studies on Indian ethnic groups from different regions are necessary to find out
      the importance of allele 18 as the predominant allele in Indian population.

PMID- 15739384
TI  - mtDNA sequences of Chadic-speaking populations from northern Cameroon suggest
      their affinities with eastern Africa.
AB  - BACKGROUND: No mitochondrial DNA (mtDNA) sequences from Chadic-speaking peoples
      have yet been reported, even though these populations inhabit a vast territory
      from eastern Nigeria to central Chad. This paper deals with the mtDNA sequences
      of four Central Chadic populations (Hide, Kotoko, Mafa and Masa) from northern
      Cameroon, biological samples from which were collected during anthropological
      research in the area of their homeland. OBJECTIVE: The main goals of this article
      are to report new mtDNA sequences of Chadic-speaking populations, to analyse
      their genetic diversity and to establish their relationships within the peri
      Saharan area in respect of geography and languages. SUBJECT AND METHODS: The
      analyses are based on 104 mtDNA haplotypes, which can be localized into four
      different areas of northern Cameroon. Data collection was based on a strict
      geographical sampling strategy; the ethnonyms are retained here only for
      comparative purposes. RESULTS: None of the examined Chadic populations displays a
      departure from the normal mismatch distribution pattern, and the null hypothesis
      of the expansion event cannot be rejected. Analyses of molecular variance and
      F(ST) genetic distances revealed that the Chadic-speaking groups of northern
      Cameroon share more similarities with the populations of the Upper and Middle
      Nile Valley and East Africa than with populations from Central Africa. The
      results show geographical clustering to be more important than the correlation of
      linguistic affiliations with molecular genetic data. CONCLUSION: The observation
      that the Chadic group reveals some affinities to East Africans is extremely
      surprising giving the present-day geographical distance (around 2000 km) between
      them. These observations complement recent linguistic and archaeological
      findings, which consider the Chadic branch in the Afro-Asiatic phylum to be of
      eastern origin. A continuous, well-defined, geographic sampling strategy of the
      different genetic polymorphisms of the native populations of sub-Saharan Africa
      is further needed as the only way of understanding the differentiation of the
      mtDNA sequences at a micro-regional scale.

PMID- 15739385
TI  - Accuracy of body mass index in detecting an elevated alanine aminotransferase
      level in adolescents.
AB  - AIM: We evaluated the accuracy of body mass index (BMI) in detecting an elevated
      alanine aminotransferase (ALT) level in adolescents, taking into account the
      effects of gender, age, ethanol intake, hepatitis B virus (HBV) and hepatitis C
      virus (HCV) infections, and drug consumption. SUBJECTS: A representative sample
      of 454 adolescents (11-17 years) from two cities in northern Italy was studied
      (the Dionysos Study). METHODS: z-BMI was calculated as the z-score of BMI using
      national growth charts. Logistic regression was used to quantify the contribution
      of the variables of interest to an elevated ALT (> 30 UL(-1)). Odds ratios (OR)
      and 95% confidence intervals (95% CI) were calculated, and areas under receiver
      operator characteristic curves (AUC) were used to evaluate accuracy. RESULTS: An
      elevated ALT was detected in 21 adolescents (4.6%). Among the studied variables,
      only male gender (OR=6.7, 95% CI 2.0-23.2) and z-BMI (OR=2.1, 95% CI 1.4-3.2)
      were significant predictors of elevated ALT. The accuracy of the prediction was
      0.69 (95% CI 0.59-0.79) for gender and 0.71 (95% CI 0.59-0.81) for z-BMI. By
      combining gender and z-BMI, the accuracy rose to 0.80 (95% CI 0.71-0.89).
      CONCLUSION: BMI is a good predictor of elevated ALT in Italian adolescents and
      gender adds to the accuracy of the prediction.

PMID- 15739387
TI  - Limitations to the use of secondary sex characteristics for gender comparisons.
AB  - BACKGROUND: To control for the confounding effect of maturation many researchers
      use secondary sex characteristics to compare individuals within and between
      genders. However, this assumption presumes that the timing and tempo of secondary
      sex characteristics is identical in both genders. AIM: The study investigated the
      timing and relationships between sexual and somatic maturation indices between
      and within genders. SUBJECTS AND METHODS: Eighty three boys and 75 girls, aged
      between 8 and 15 years at study entry, were measured every 6 months for 6
      consecutive years. Sexual maturation was assessed through pubic hair, facial hair
      and axillary hair development in boys, and pubic hair development and menarcheal
      status in girls. Somatic maturation was assessed through age at peak height
      velocity (PHV). RESULTS: Low to moderate correlations (r = 0.30-0.55, p < 0.05)
      existed between age of PHV and age of reaching each pubic hair stage. The
      majority of boys reached PHV in pubic hair stage 4 (79.2%). The majority of girls
      reached PHV in pubic hair stage 3 (42.5%) and pubic hair stage 4 (47.5%).
      CONCLUSION: Boys and girls differ in the timing and tempo of somatic and sexual
      maturity. Thus boys and girls should not be aligned on secondary sex
      characteristics when controlling for the confounding effects of maturity.

PMID- 15739386
TI  - Distribution of apolipoprotein E allele frequencies of the Han Chinese in an
      iodine-deficient mountainous area.
AB  - BACKGROUND: Iodine deficiency is common in the Qinba mountainous area and fetal
      iodine deficiency disorder (FIDD) is endemic. Our previous study demonstrated
      that apolipoprotein E (ApoE) was a genetic risk factor for FIDD in the local
      area. AIM: In order to achieve a better understanding of the aetiology of iodine
      deficiency-based mental retardation in the Qinba mountainous area, we conducted
      further studies of ApoE allele frequencies obtained from the local population.
      SUBJECTS AND METHODS: A total of 818 samples from four counties in the iodine
      deficient area were recruited for the study of the ApoE genotype and allele
      frequencies using the PCR-RFLP method, and were subsequently confirmed by
      sequencing. RESULTS: The frequencies of epsilon2, epsilon3 and epsilon4 alleles
      of Han Chinese in Qinba were 9.67%, 81.30% and 9.03%, respectively. Furthermore,
      no significant differences in the distribution of ApoE (either genotype or allele
      frequencies) between any two subgroups divided according to location, sex and age
      (p > 0.05) were found. Surprisingly, however, we found a significant difference
      in the genotype and allele frequencies between Qinba and Shanghai (genotype: chi2
      = 14.91, p = 0.0096; allele: chi2 = 15.07, p = 0.0009). CONCLUSION: The currently
      documented allele frequencies of ApoE in the Han Chinese population living in the
      open areas of China do not represent the distribution in the isolated Qinba
      mountainous area. The higher level of epsilon2 and epsilon4 allele frequencies in
      the Han Chinese living in the isolated Qinba area arise by chance or may result
      from genetic adaptation to an environment characterized by malnutrition and
      iodine deficiency, which may also contribute to the high incidence of mental
      retardation in these regions.

PMID- 15739388
TI  - [The development of a gas chromatograph used in gas analysis below atmospheric
      pressure].
AB  - During the process of setting up a carbon monoxide infrared laser generator, it's
      necessary to analyze the gaseous components produced in laser cavity under
      reduced pressure for understanding its charging regularity. In this paper a self
      made gas chromatograph for analysis of some special gas mixtures is described.
      This instrument can analyze O2, N2, CO (with normal contents) and trace CO2
      simultaneously below atmospheric pressure. The gas sample below atmospheric
      pressure was taken into a small piston cylinder and then compressed by pushing
      the piston for injection. The injected sample was carried by He into two parallel
      chromatographic columns and detected separately. The gases with normal contents
      were detected by a thermalconductivity detector (TCD) and the trace CO2 was
      detected by a He ionization detector (HeID). The detection sensitivity of CO2 is
      in the order of magnitude of 10(-6) V/V. The experimental results show that this
      instrument with advantages of simple design, easy operation and good stability is
      suitable for on-line analysis of gas samples below atmospheric pressure. We have
      successfully analyzed on-line the gaseous components produced in the laser cavity
      by using this equipment. The technique described here can be used for complete
      analysis of gas samples below atmospheric pressure in many other fields.

PMID- 15739389
TI  - [Prediction of RP-HPLC retention index for hydroxyl-containing compounds and
      their glucuronides].
AB  - The quantitative relationships between the structure of solutes and their
      chromatographic retention behaviors have been widely studied. A lot of compounds
      have been investigated, but drug metabolites have not been involved.
      Determination of glucuronic acid conjugation is the most important route for
      investigations of metabolism of drug, while the glucuronide samples are rarely
      obtained. In this paper the glucuronides have been obtained with the method of
      biosynthesis in vitro. The peaks of glucuronides were identified by several means
      including diode-array spectrophotometer detection, beta-D-glucuronidase
      hydrolysis, glucuronide references and chromatogram comparison of the incubation
      samples at different times. Two systems have been developed to predict retention
      index in reversed-phase high performance liquid chromatography based on the
      molecular structure of the analytes and on the behavior of the parent compounds.
      We observed a good correlation between retention index of hydroxyl-containing
      compounds of glucuronides and hydrophobility based on Hansh pi value:
      I=383.4+136.0pi, n=10, r=0.9912. A good correlation between hydroxyl-containing
      compounds and their glucuronides was also observed: Y=-471.1+1.4430X, n=11,
      r=0.9600. The errors in this experiment are less than 12%.

PMID- 15739390
TI  - [Determination of stability constants of metal complexes by on-column
      derivatization reversed phase high performance liquid chromatography].
AB  - The stability constant of metal complexes is an important chemical parameter.
      There are many methods for its determination, but few analyst has calculated it
      with high performance liquid chromatography (HPLC). In the present paper a new
      model for determining the stability constant of metal complexes with on-column
      derivatization reversed phase HPLC has been proposed where complexation forming
      reactions are taking place in the mobile phase. Based on the retention mechanism
      of neutral complexes, the equation for calculation is deduced. It has been
      applied to some cations (Hg2+, Pb2+, Ni2+, Cu2+, Ag+, Hg+)-DDTC complexes. The
      results are in agreement with those given in the literature. Then, a simple,
      practical and rapid graphic method is studied for monovalent metal complexes. The
      stability constants can be obtained simply as the quotient of the line slope and
      the axis intercept of the linear dependence. The relations derived in this paper
      may be used not only for calculating the stability constants from chromatographic
      measurements but also for optimizing the process of separation based on the
      values of the stability constants available in literature.

PMID- 15739391
TI  - [Determination of steroids in milk powder and birds' feces by high performance
      liquid chromatography coupled with evaporative light scattering detector].
AB  - In this paper, a new, simple and rapid method for the analysis of steroids by
      reversed-phase high performance liquid chromatography (HPLC) coupled with
      evaporative light scattering detector (ELSD) is presented. A good resolution of
      the 12 steroids is obtained within 35 min with a gradient elution using a binary
      mobile phase composed of methanol and water. The analytical column used was 2.0mm
      x 150mm, packed with BDS (particle size 5microm) and the mobile phase flow rate
      was 0.2mL/min. Nebulizer gas flow rate and drift tube temperature, the two
      critical parameters for determining the reproducibility and signal-to-noise ratio
      of ELSD were 2.00mL/min and 95 degrees C, respectively. The response of the ELSD
      was non-linear as a result of basic light-scattering principles, the calibration
      curve by plotting lnY vs lnX (Y, X stand for peak area and concentration,
      respectively) shows a good linearity in the range of 5-50mg/L with a correlation
      coefficient higher than 0.99 for individual steroid and with relative standard
      deviation less than 6.92%. This method has been applied to the determination of
      steroids in milk powder and birds' feces, solid phase extraction on reverse phase
      bonded C18 (5mL/500mg) was used to treat the samples efficiently. The recoveries
      of the steroids were between 84.0%-102.8%.

PMID- 15739392
TI  - [Preliminary study on planar two-dimensional capillary electrophoresis].
AB  - Capillary Electrophoresis (CE) system with rectangular cross section columns is
      integrated on quartz monocrystal plate. Because of its high surface-to-volume
      ratio and excellent heat conductivity of quartz, rectangular capillary is
      extremely efficient in dissipating heat compared to conventional circular
      capillaries. Comparative study showed that much higher electric field strength
      can be applied to this system without bubble formation. Another advantage of
      rectangular geometry channel is better detection ability because of the
      elimination of optical path distortion. The effectiveness of the planar CE has
      been demonstrated by comparing the separation of two solutes in phosphate buffer
      between rectangular and circular cross section column with same area. We also
      found that the separation efficiency can be improved dramatically by decreasing
      the channel dimension, which underlies the miniaturization of planar CE. In
      addition, injection by micro injector eliminate sample biasing and increase
      reproductivity. A simple manifold of rectangular flow channels are fabricated on
      quartz substrate. By use of electroosmotic pumping it is possible to control the
      direction of fluid flow in the manifold of intersecting channels without the use
      of valves. The experimental results proved that the band dispersion after the
      valveless switching is almost negligible, showing that the two dimensional
      separation is possible. The main contribution to band-broadening in our capillary
      electrophoresis is longitudinal diffusion, injection delay time and wall
      adsorption. In some cases the wall adsorption make the most contribution. Optimum
      efficiency depends on minimization of these unavoidable sources causing band
      broadening.

PMID- 15739393
TI  - [Study on separating characteristics in capillary reversed-phase
      electrochromatography].
AB  - Capillary Electrochromatography (CEC) driven by electroosmotic flow is a new
      technique using fused silica capillaries packed with HPLC-type stationary phase.
      The analytes are separated by normal chromatographic partition between a mobile
      phase and a stationary phase. By using electroosmotic flow driving mobile phase,
      CEC promises theoretical plate efficiencies for HPLC. In this paper, some
      separating characteristics in capillary electrochromatography were studied by
      carrying out the separation of some neutral compounds on capillary column with
      75microm i.d. x 30cm/37cm packed with ODS particles (3microm). The mobile phase
      was acetonitrile and water, which contains certain concentration of electrolyte.
      Samples were injected electrokinetically into the separating column. On-line UV
      detector was used. The Joule heating effect in packed CEC was lower than that in
      CZE, and a good linear relationship between the elecrtoosmotic flow (EOF)
      velocity and applied voltage was obtained as shown in Fig. 1. The influence of
      electrolyte and acetonitrile concentrations on the electroosmotic flow was
      studied, as shown in Fig. 2 and 5. The EOF was monitored by using thiourea as a
      marker. The EOF will decrease when the electrolyte concentration increases. The
      higher the acetonitrile concentration was, the lower the EOF was. The effect of
      linear velocity on column efficiencies was also investigated. The column
      effeciencies less than 2. 0 reduced plate height were obtained. The highest
      efficiency obtained in this work was 236000 plate per meter for a retained
      solute, benzene. It was found that the concentrations of acetonitrile and
      electrolyte were important experimental variables in performance of capillary
      electrochromatography.

PMID- 15739394
TI  - [Advances in research of hydrophobic interaction chromatographic packings].
AB  - Hydrophobic interaction chromatography (HIC) is an attractive method for protein
      purification. The paper gives a review on the characteristics of HIC packings,
      including matrices and hydrophobic ligands. The efficiencies for protein
      separations were compared for different HIC packings. The present situation and
      the developing trends of the preparative HIC packings were described.

PMID- 15739395
TI  - [A new separation and extraction method--solid-phase micro-extraction].
AB  - The principle and application of a new sample preparation method--solid-phase
      micro-extraction (SPME) are introduced in this paper. An SPME unit consists of a
      certain length of fused silica fiber coated with stationary phase, and a holder
      which looks like a microliter syringe. Organic analytes are adsorbed by the
      fiber, and is directly introduced into the GC injector, where the adsorbed
      analytes are desorbed. SPME can be used to concentrate volatile and nonvolatile
      compounds in both liquid and gaseous samples without the use of solvents and
      provides low detection limits. The technique is more favorable in comparing with
      other sample preparation methods.

PMID- 15739396
TI  - [LC troubleshooting--solvent selection: physical properties].

PMID- 15739397
TI  - [A simple method for analyzing insect pheromone at the nanogram level by coupling
      headspace adsorption and thermal desorption injection by gas chromatography with
      a packed syringe].
AB  - This paper describes a simple device for analysis of insect pheromones by
      coupling headspace adsorption and direct nonsolvent thermal desorption injection
      by gas chromatography (GC). A microsyringe packed with Porapak Q as the adsorbent
      was mounted in the airway for enriching and collecting pheromones. After
      collection the microsyringe was inserted into a thermal desorption device which
      was coupled with a GC inlet port. The pheromone desorbed from the adsorbent was
      condensed on the cold head of the GC column and injected into the column by
      quickly increasing the temperature of the column oven. The synthetic compounds of
      insect pheromones, E-7-dodecyl acetate (E-7-DA) and Z-5, E-7-dodecadienyl acetate
      (Z-5, E-7-DDA), were used to determine the recovery of the method and to evaluate
      the utility of this device for GC analysis of insect pheromones at the nanogram
      level. The results demonstrated the potentials of this device for GC analysis of
      volatile components both on packed columns and capillary columns. The advantage
      of headspace collection is that it avoids interference from non-volatile
      contaminants and the advantage of nonsolvent thermal desorption injection is to
      avoid the loss of pheromone while concentrating the eluted solution. The reported
      method combines these two advantages. The author also discusses the ways to
      further improve the method.

PMID- 15739398
TI  - [Gas chromatographic analysis of fatty acids in phosphatidylglycerol from needles
      of two crosses of Chinese Fir].
AB  - This paper reports a method for determination of fatty acids in
      phosphatidylglycerol from needles of two crosses of Chinese Fir with different
      cold-resistance. Some simplifications and improvements for analytical method of
      DEAE CL-6B column chromatography and of silica thin layer chromatography were
      also discussed. After being extracted with chloroform and methanol,
      phosphatidylglycerol was isolated from the general lipid extract by using DEAE CL
      6B IEC and Silica TLC. Quantitative analysis was conducted by gas chromatography
      on a DB-FFAP (30m x 0.32mm i.d.) column. The results showed that there was a
      difference in the ratio of fatty acid (18:1+18:2+18:3)/[16:0+16:1(3t)] between
      the two crosses of Chinese Fir with different cold-resistance, 1.12 for that with
      higher cold-resistance and 1.25 for that with lower cold-resistance. A special
      fatty acid 16:1(3t) was found in both of the two crosses.

PMID- 15739399
TI  - [Analysis of the stereoisomers of 14 pyrethroids by capillary gas
      chromatography].
AB  - The separation of stereoisomers of 14 pyrethroids has been studied by capillary
      gas chromatography. The pyrethroids are cypermethrin (P1), phenothrin (P2),
      allethrin (P3), prallethrin (P4), tetramethrin (P5), permethrin (P6), cyfluthrin
      (P7), fenvalerate (P8), flucythrinate (P9), bromofenvalerate (P10), fluvalinate
      (P11), methothrin (P12), resmethrin (P13) and py115 (P14). The gas
      chromatographic conditions were as follows. Column 1: fused silica, 10m x 0.53mm
      x 1.0microm film (QF-1); columntemperature: 180 degrees C-260 degrees C depending
      on the pyrethroids analysed; the temperature of injector and detector: 280
      degrees C; carrier gas: H2 4.6mL/min; detector: FID; spilt ratio: 5:1, sample
      size 1.0 L. The stereoisomers of P2, P3, P4, P5, P6, P8, P9, P10, P12 and P10 can
      be completely separated by QF-1 column. However the stereoisomers of P11 can not
      be separated and the three peaks of P1 and P7 have been only separated by column
      1. In comparing with packed column of QF-1, there are advantages in superior
      resolution, lower oven temperature and shorter analysis time for capillary column
      of QF-1. Column 2: fused silica HP-5 (crosslinked 5% phenyl methyl silicone) 25m
      x 0.32mm x 1.0microm film; column temperature: P1 and P7 250 degrees C, P11 260
      degrees C, and P14 200 degrees C; carrier gas: H2 2.6mL/min. Other conditions
      were the same as the column 1 described. The stereoisomers of P1, P7, P11 and P14
      can be separated, but the separation of stereoisomers was not sufficient. The
      stereoisomers of P2, P5, P6, P8, P9, P10, P12 and P13 can be completely separated
      by HP-5 capillary column. However separation on the HP-5 capillary column is not
      sufficient for diastereoisomers of P3 and P4.

PMID- 15739400
TI  - [Determination of alkylmercuric compounds in human body fluids by gas
      chromatography--atomic absorption spectrophotometry].
AB  - In order to detect trace of alkylmercuric compounds in human body fluids, a
      highly sensitive, selective and rapid method, based on the coupling of gas
      chromatography with atomic absorption spectrophotometry, has been developed. The
      transfer-tube was made up of Teflon, with stainless steel tubes in the two sides.
      The atomization of alkylmercuric compounds was performed in quartz tube. The
      quantitative determination of alkylmercuric compounds in urine and blood samples
      collected from the workers exposing to metallic mercury, has been extensively
      carried out in this work. The optimal Westoo program was used to enrich
      methylmercuric chloride in samples, Extracts of methylmercuric chloride in
      benzene were determined by GC-AAS, with a total recovery of more than 90%.
      Dimethylmercury in samples was extracted once by xylene. Then the extracts were
      determined, with a total recovery of 65%-70%. The detectable limit for mercury
      was 0.01ng. The methylation of mercury was confirmed in our experiment. This
      method can be used for the determination of other metallic compounds.

PMID- 15739401
TI  - [Simultaneous determination of carotenoids and chlorophylls in algae by high
      performance liquid chromatography].
AB  - An isocratic reversed-phase HPLC method for the simultaneous determination of
      carotenoids and chlorophylls in algae is presented. Both carotenoids and
      chlorophylls were separated by using a C18 column and a mobile phase consisting
      of dichloromethane/acetonitrile/methanol/water (22.5:9.5:67.5:0.5). The flow rate
      was 1.0mL/min. These pigments were detected by a UV-VIS absorbance detector set
      at 450nm. The average recoveries of these pigments by standard addition method
      were 99.1% for lutein, 98.5% for alpha-carotene, 99.4% for beta-carotene, 100.6%
      for chlorophyll a and 99.9% for chlorophyll b. The relative standard deviations
      of these pigments were 2.4% for lutein, 5.6% for alpha-carotene, 6.0% for beta
      carotene, 4.1% for chlorophyll a and 4.0% for chlorophyll b. The calibration
      curves for these pigments gave good linearity over a wide range of 0-50mg/L (r =
      0.9992-0.9999). The retention times were 3.0 min for lutein, 4.7 min for
      chlorophyll b, 6.3 min for chlorophyll a, 14.1 min for alpha-carotene, and 14.7
      min for beta-carotene. Using this method, carotenoids and chlorophylls were
      determined in Spirulina platensis, Chlorella vulgaris and Haematococcus
      lacustris. Chlorella vulgaris and Haematococcus lacustris samples were ground in
      a B. Braun homogenizer. Spirulina platensis sample was smashed by supersonic
      wave. Acetone was used as extractant.

PMID- 15739402
TI  - [Study on the separation and determination of phthalates in plants].
AB  - A convenient and efficient method for analysis of phthalate esters (PEs) in
      plants was developed. PEs in plants were extracted with dichloromethane by
      ultrasonication, separated by chromatography with a column chromatography packed
      with 10-40microm sillica and then determined by HPLC on a 250mm x 4.6mm i.d. ODS
      column using MeOH/H2O (88:12) as mobile phase and UV detection at 228nm. The
      minimum detectable limits for diethyl phthalate (DEP) and diethylhexyl phthalate
      (DEHP) were 47pg and 85pg respectively. The overall recoveries of PEs were found
      to be 85%-101%. The method has been satisfactorily applied to the determination
      of plant samples.

PMID- 15739403
TI  - [Study on microwave hydrolysis for the analysis of amino acids in egg by high
      performance liquid chromatography].
AB  - A new hydrolysis method which only needs 7min--microwave hydrolysis used for the
      analysis of amino acids in egg by Pico-Tag high performance liquid chromatography
      (HPLC) is reported. The experimental results show that the satisfactory recovery
      could be obtained by use of 6mol/L HCL and 1% phenol as hydrolysing solution and
      a microwave oven with power of 300W. These conditions can also be used for the
      hydrolysis of other samples, such as rice, meat and so on. The average recovery
      of this method is 95% with a RSD of 2%. The accuracy is better than the
      conventional one (hydrolysis 24 at 110 degrees C) and Pico-Tag (hydrolysis 24h at
      105 degrees C). Furthermore, the microwave hydrolysis decreases the loss of some
      unstable amino acids, e.g. Ser, Thr, Tyr, etc. In the process the method is
      convenient, rapid, accurate and reproducible.

PMID- 15739404
TI  - [Studies on the separation method with multiple injection of proteins].
AB  - An abrupt change of the eluting curve of proteins in the RPC and HIC was reported
      in the previous paper. Here, we present a new multi-injection method of proteins
      in which the sample may be injected for many times in the same chromatographic
      run. When the composition of mobile phase is far away from the position of the
      abrupt change, the multi-injection of proteins before and/or after starting a
      gradient elution for one chromatographic separation in the RPC and HIC can be
      performed. Thus we may obtain the same chromatogram and retention of proteins as
      the ordinary one. This method can be used to overcome the difficulty that the
      loop is too small for injection big volume of sample solution. A larger sample
      size can be injected by many times in one chromatographic run to save time and to
      decrease the consumption of the experimental material. If there exist some impure
      proteins of weak retention, the impure proteins may go through the column with
      the solution A when the selected concentration of mobile phase is suitable.
      Therefore, a fixed column size can adsorb more related proteins, that is the
      effective column capacity is relatively raised. This injection method has an
      important value in the preparative chromatography of proteins.

PMID- 15739405
TI  - [Determination of degradation level of antifungal agent in mice serum by high
      performance liquid chromatography].
AB  - L-4-oxalysinyl-norvalinyl-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (I-677
      Nva-FMDP) is a new tripeptide synthesized in our group. This peptide exhibits
      potent anticandida Albicans activity. In the presence of serum, the antifun gal
      activity of I-677-Nva-FMDP decreases after incubating over 1h. In order to
      investigate the relationship between the degradation and antifungal activity of I
      677-Nva-FMDP, the concentrations of I-677-Nva-FMDP and N3-methoxyfumaroyl-L-2,3
      diaminopropanoic acid (FMDP) were determined at different incubating time in mice
      serum. The incubating time range was from 0 to 300 min and the incubating samples
      were measured at intervals of 30 min. For this measurement reversed-phase HPLC
      was used and the mobile phase was composed of 8% methanol and 0.1%
      trifluoroacitic acid-triethyl amine buffer (pH 3). In this condition the
      retention time of FMDP and I-677-Nva-FMDP were 3.9 min and 16.5 min respectively.
      Methanol was superior to other reagents for the removal of protein from the
      incubating medium and there was not any interference peak before the retention
      time of I-677-Nva-FMDP. A decrease in concentration of I-677-Nva-FMDP was
      observed from 0 min to 180 min and no I-677-Nva-FMDP could be detected at 210 min
      whereas the concentration of FMDP incresed from 30 min to 2h and reached a
      maximum at 120 min. The results showed that the half life (t1/2) of I-677-Nva
      FMDP was 70 min. This result coincided with the antifungal test in vitro.

PMID- 15739406
TI  - [High performance gel chromatographic behaviour of sodium alginate and
      determination of its molecular weight parameters].
AB  - The molecular weight parameters of sodium alginate were determined by high
      performance gel chromatography with Waters Bondagel E-High A column. The
      differences in high performance gel chromatographic behaviours between the sodium
      alginate and the non-polar standard Dextran T500 were compared. The influences of
      the sample concentration and the sample volume on the results were discussed. The
      high performance gel chromatographic behaviour of sodium alginate is different
      from that of Dextran T500, and is also different from those on Sepharose or
      Sephadex columns. The peak shifted toward full osmotic side under in crease of
      ionic strength. The elution volumn didn't tend toward stable, even though at the
      high concentration of 0.5mol/L NaCl. A change of the sample concentration at
      stable sample volume or the sample volume at stable sample concentration would
      cause tailing peaks. It was showed that the sample size of sodium alginate would
      be less than 25microg, and the relative standard deviations of Mn, Mw and d were
      0.95%, 4.04% and 4.70%.

PMID- 15739407
TI  - [Studies on polysaccharide peptide with high performance gel permeation
      chromatography].
AB  - High performance gel permeation chromatography (HPGPC) has been widely used in
      the fraction and molecular-weight (MW) estimation of polysaccharides. In this
      paper, we estimated the MW of major component of polysaccharide-peptide from
      Corilous versicolor (PSP). These three-components were separated by using two
      column system (TSK-40 and TSK-50 gel columns) and different NaCl concentration in
      mobile phase. Calibration curve was prepared from the known MW Dextran T-system.
      It was found that the MW of PSP was changed in accordance with ion concentration
      of mobile phase. The MWs of the main component are more than 500000, 120000-19000
      and less than 10000 respectively as the NaCl concentrations in mobile phase were
      less than 0.002, 0.006-0.04 and more than 0.06mol/L. The results showed that the
      MW of polysaccharide-peptide determined by HPGPC is a relative value that is
      changed with the concentration of mobile phase. The reason is that the molecular
      configuration and size of polysaccharide-peptide are changed along with
      electrolyte concentration in mobile phase. That is, the lower the electrolyte
      concentration is, the larger the molecular size of polysaccharide-peptide is. We
      suggest that it is still useful for quality control of PSP as the mobile phase is
      fixed.

PMID- 15739409
TI  - [Study on the micellar electrokinetic capillary chromatography (MECC) for several
      water soluble vitamins].
AB  - In the paper, the influences of the concentration of sodium dodecyl sulphate
      (SDS) and borax (Na2B4O7), pH value and applied voltage on the MECC of water
      soluble vitamins--VB1, VB2, VB6, VB12 and VC in fused silica capillary were
      studied. In the system of SDS-Na2B4O7, the retention times of the vitamins
      mentioned above increase with the increase of concentration of SDS and Na2B4O7.
      But if SDS concentration is too high the separation will become worse, and if
      Na2B4O7 concentration is too high the peak will be broad because the increase of
      retention time will lead to the increase of diffusion of molecules. With the pH
      increasing, the separation efficiency is always increasing. The change of the
      applied voltage has little effect on the separation efficiency. However, at
      higher pH and applied voltage, the high ionic strength and large current will
      produce more Joule heat and cause higher background noise. The optimum run buffer
      for this separation contains 18mmol/L Na2B4O7 and 25mmol/L SDS, with pH at 8.5 by
      adjusted with hydrochloric acid. The separation was completed within 4min at an
      applied voltage of 14.0kV. The separation efficiencies ranged from 1.1 x 10(5) to
      2.4 x 10(5) theoretical plates/meter. The application of this method to drug
      analysis is demonstrated.

PMID- 15739408
TI  - [Isolation and determination of the seeds of Pachyrrhizus errosus protein by high
      performance gel filtration chromatography (GFC)].
AB  - From the seeds of Pachyrrhizus errosus, three protein constituents, namel PE1,
      PE2 and PE3, have been isolated and purified by extraction with 5mmol/L phosphate
      saline (0.9% NaCl) buffer (PB) at pH 7.2, and S-Sepharose Fast Flow Column (2.6cm
      x 15cm) chromatography which eluted with 5mmol/L phosphate buffer (pH 7.0)
      containing 1mmol/L NaCl. Three proteins were burther separated on two connected
      Protein-Pak 60+Protein-Pak 125 [7.5mm x 39cm, 10microm] columns with mobile phase
      of 0.2mol/L phosphate buffer (pH 6.5). The flow rate was kept constant at
      0.8mL/min by YSB-2 type high press pump. The effluent was monitored at a
      wavelength of 280nm on photodiode array detector. These three proteins are proved
      to be homogeneous by SDS-PAGE, IEF and HPGFC experiments, and all present the
      typical absorption spectra in ultraviolet region. The moleculer weights of the
      three proteins are approxiamtely 33000D, 14500D and 14000D respectively by SDS
      PAGE. But as using HPGFC analysis, the MW value of PE2 is 28000D. This indicates
      PE2 may be composed of two chains joined by disulfide bond, which is further
      proved from the latter amino acid composition analysis. The isoelectric points of
      three proteins are 4.5, 6.5 and 7.5 respectively by using IEF. The amion acids
      compositions of the three proteins were determined with OPA post-column
      derivatization/fluorescence detection.

PMID- 15739410
TI  - [Analysis of PTH amino acids by micellar electrokinetic capillary
      chromatography].
AB  - A useful method for separation of 19 PTH amino acids by micellar electrokinetic
      capillary chromatography has been developed. Experiments were performed at 35
      degrees C with 14kV power, 50microm x 57cm fused-silica capillary column and UV
      absorption detector. Each new capillary was washed with 0.1mol/L NaOH and
      deionized water, each for 15min, before use. Samples were injected into the
      capillary by applying pressure (3402Pa) for 5s. Absorption detection was at
      200nm. The running buffer was made up of 50mmol/L sodium dodecyl sulfate (SDS),
      50mmol/L sodium of phosphate and borate (pH 7. 0). The infulence of operation
      voltage, pH of buffer, temperature and SDS concentration on the amino acids
      migration has been studied. The coefficients of variaton of migration time and
      peak area of 19 PTH amino acids were below 1.0% and 5.0% respectively. The
      detection limits were 0.1-0.25pmol.

PMID- 15739411
TI  - [The development of a new type of SnO2/SnCl2 semiconductor as detector in gas
      chromatography].
AB  - A new type of SnO2/SnCl2 semiconductor as detector in gas chromatography has been
      developed. The sensing crystalloid with SnO2 as main block has an outstanding
      sensitivity to the reducing gases in a certain oxidative circumstance. The
      reducing gases can be reversibly adsorbed on the surface of crystal and make the
      resistance of the sensing element changed. Therefore, this type of sensing
      element may be used as detector in GC. We studied and prepared such sensing
      element with SnCl2 as catalyst to improve the sensitivity. An optimum
      procedurefor preparation has been received. We also discussed the possibilily as
      the gas-sensing element to replace the flame ionization detector in GC. The
      results showed that at the condition of 300 degrees C, the sensitivity,
      stability, detectability and linear range were satisfactory. This new type of
      detector can meet the needs of practical sample analysis.

PMID- 15739412
TI  - [Determination of 5-fluorouracil in human serum by high performance liquid
      chromatography].
AB  - A reversed-phase HPLC method is described for determination of 5-fluorouracil in
      human serum. After being extracted with ethyl acetate 5-fluorouracil was analyzed
      by reversed-phase HPLC column (Zorbax ODS) and UV-detector (273nm) with tegaful
      as internal standard. The mobile phase was a mixture of methyl alcohol and water
      (20:80, V:V) at a flow rate of 1mL/min. The linear range was 0.04-50mg/L
      (r=0.9990) and the detectable limit was 10ng/mL. The average recovery was 96.85%
      and the coefficients of variation were 4.38% and 5.37% for within-day and day-to
      day tests respectively.

PMID- 15739414
TI  - [The determination of enantiomeric purity for 1,1'-binaphthyl-2,2'-diol by high
      performance liquid chromatography].
AB  - In the past few years, much attention has been focused on the studies of the
      chirality recognition properties of chiral crown ether hosts containing the
      binaphthyl unit. The application of chiral 1,1'-binaphthyl-2,2'-diol (1) in
      asymmetric synthesis has been proved fruitful. Consequently, the preparation of
      optically active binaphthol and the determination of its enantiomeric purity is
      of current interest. In this paper, an efficient HPLC method for determination of
      enantiomeric purity of 1,1'-binaphthyl-2,2'-diol (1) through formation of a
      couple of diastereomers, (R)-1,1'-binaphthyl-2,2'-diyl-N-(S)-(alpha-methylbenzyl)
      phosphoramidate (R,S)-2 and (S)-1,1'-binaphthyl-2,2'-diyl-N-(S)-(alpha
      methylbenzyl)phosphoramidate (S,S)-2, is described by using Micropak Si-5 column,
      petroleum and ethanol (7:3, V/V) as eluate and UV detector (lambda = 300nm). The
      method is convenient, rapid and accurate. The accuracy was between 98.6%-101.6%,
      and the average deviation was 1.01%.

PMID- 15739413
TI  - [Determination of icariin in Epimedium koreanum nakai by high performance liquid
      chromatography].
AB  - An HPLC method for determination of icariin in epimedium koreanum nakai was
      investigated. The results showed that this method was simple, specific and
      accurate. The recovery was 97.6% and relative standard deviation was 1.2%. About
      0.5 g of dried powdered crude drug was weighed accurately, placed in 25 mL of the
      mobile phase and refluxed on a water-bath for 30 min. After cooling, the solution
      was decanted. The residue was refluxed twice with 10 mL of the mobile phase. The
      extract were placed in a 50 mL volumetric flask and diluted to 50 mL with the
      mobile phase. A 3 microL of the solution was injected into the HPLC system.
      Linear calibration graphs for icariin were obtained for the concentration ranges
      of 0.08-0.4 microg. HPLC conditions were used was Shimadzu LC-6A with UV
      spectrometric detector SPD-6AV; at 270 nm and auto injector SIL-6A. Water
      acetonitrile (70:30) as the mobile phase, Shim-pack CLC-ODS column (6.0 mm x 150
      mm).

PMID- 15739415
TI  - [Determination of metronidazole in serum and cerebrospinal fluid with reversed
      phase high performance liquid chromatography].
AB  - A reversed-phase high performance liquid chromatographic method for the
      determination of metronidazole (MTZ) in rabbit serum and cerebro-spinal fluid has
      been developed. The method is simple and convenient. The analysis was carried out
      with Zorbax C8 column, NaH2PO4(0.0075mol/L, pH 4.0)-CH3OH(4:11) as mobile phase
      and UV detector at 320nm, by using hydrochlorothiazide as internal standard. The
      standard curve is linear over the range from 0.5ng/L to 80.0ng/L in sample with
      correlation coefficient of 0.9998. The recovery of metronidazole from rabbits
      serum and cerebrospinal fluid are 97.1% +/- 1.5% and 97.4% +/- 1.6% respectively.
      The minimum detectable quantity is 80ng/mL in sample (S/N = 3). Under the
      chromotographic condition, the consistency of MTZ of the serum and cerebrospinal
      fluids of rabbits were detected separately after taking MTZ (0.1mg/g) orally. The
      drug-time curve was obtained and a satisfactory result was achieved. The new
      findings provide conditions for further exploration of the process of
      pharmacokinetics.

PMID- 15739416
TI  - [Indirect UV detection of short chain carboxylic acids in oil field water by high
      performance capillary zone electrophoresis].
AB  - Short chain carboxylic acids are the major aqueous organic species in oil field
      water. It is considered that they play an important role in the geochemical
      evolution of second porosity in oil reservoir. In this paper, short chain
      carboxylic acid anions were analyzed by HP(3D)CE high performance capillary
      electrophoresis system (Hewlett-Packard, Germany) with a buffer system of
      dinitrobenzoic acid-hexadecyltrimethyl ammonium bromide (CTAB). The influence of
      buffer pH and the concentrations of electrolyte, surfactant and methanol on the
      seperation of short chain carboxylic acids have been studied. The results showed
      that the best separation of short chain carboxylic acids could be done with the
      buffer of 10mmol/L dinitrobenzoic acid, 0.5mmol/L CTAB and 5% methanol at pH=9.
      Separations were performed in a 50cm x 50microm i.d. fused silica capillary
      (effective length 48.5cm) at 25 degrees C. A negative potential of 30kV was used
      for each experiment. Sample was introduced into the capillary by pressure at
      50kPa for 10s. Indirect UV detection was operated at 254nm and reference
      wavelength at 380nm for all experiments. Negative peak was changed into positive
      one by exchanging between detection wavelength and reference wavelength.
      Capillary was rinsed for 10min with 0.1mol/L sodium hydroxide and buffer solution
      before each run. Oil field water was injected directly after filtered through
      0.45microm membrane. The result was satisfactory.

PMID- 15739418
TI  - [Simultaneous analysis of theophylline, phenobarbital, amobarbital and
      carbamazepine in serum by high performance liquid chromatography].
AB  - Theophylline, phenobarbital, amobarbital and carbamazepine are the chief
      therapeutic drugs in clinical practice. Because of the differences among inter
      individuals in the metabolic clearance of these drugs and their toxicity at
      certain levels of concentration in serum, the dosage should be regulated to
      maintain a therapeutic blood drugs level. To achieve this a rapid and accurate
      assay method for drugs in blood is necessary. This paper reports that a reversed
      phase high performance liquid chromatographic (HPLC) method had been established
      for the simultaneous separation and quantitative determination of the four drugs
      in serum. The separation was performed on RP-C18 column using methanol:water
      (1:1) as mobile phase and 4-aminoantipyrime as internal standard. The eluted
      substances were detected at 210nm.

PMID- 15739417
TI  - [Enrichment and determination of trace chlorobenzene compounds in water].
AB  - In this work, by using GDX-402 porous polymer beads as adsorbent and carbon
      disulfide as eluent, the conditions for enriching trace chlorobenzene compounds
      in water were investigated. Enriched eluate was directly injected into a column
      packed with 3.0% dihexyl sulfonic acid sodium/101 white support to be separated,
      and then detected by flame ionization detector under constant temperature. The
      method has been used successfully for the determination of trace of chlorobenzene
      compounds in water.

PMID- 15739419
TI  - [Theoretical investigation of dynamic process in capillary column gas
      chromatographic system--effect of radial diffusion on elution profile].
AB  - Based on a mass balance equation, in this paper, the kinetic model of
      chromatography including influence of the radial diffusion on the mass transfer
      process is set up. Based on the hypothesis of Giddings, this model has been
      simplified. In this way, the expressions of the first moment, the second and the
      third central moment for this model are derived by Laplace transform in detail.
      The results show the radial diffusion affects not only the column efficiency, the
      peak spreading and the peak symmetry, but also the retention time.

PMID- 15739420
TI  - [Dual-wavelength method for analysis of overlapped high performance liquid
      chromatographic peaks with multiwavelength diode array detection].
AB  - High performance liquid chromatography (HPLC) is one of the analytical techniques
      most frequently used. Its chief limitation lies in the need to avoid the overlap
      of chromatographic peaks as much as possible. In this work, a new method for the
      treatment of HPLC data allowing the resolution of extensively overlapped peaks
      has been developed. This method uses a diode array spectrophotometer and treats
      the generated data by dual-wavelength method. Its foundation is based on
      calculating the peak areas for two given wavelength in order to determine the
      contribution of each component to the mixed peak. Because the area is the
      integration of absorption at different wavelength, the wavelength can be chosen
      from the absorption spectra of the two compounds for eliminating the interference
      of the other component in the mixture, and the concentration of the corresponding
      component can be calculated. This method provides a simplification of the
      calculation process and a reduction of the amount of the data used. The
      applicability of the method is checked on mixture of two aromatic nitro
      compounds. Though the two components almost have the same retention time and
      their peaks overlapped extensively, the results are satisfactory.

PMID- 15739421
TI  - [Capillary isoelectric focusing of protein].
AB  - A capillary isoelectric focusing (CIEF) method was developed for the separation
      of proteins with different pI. Uncoated capillary (57 cm x 50 microm i.d.) was
      used instead of commercial coated column because of its ease in use and a longer
      lifetime. Polymeric additive, methylcellulose (MC-1500), acts as dynamic coating
      of the silica wall to suppress electroendosmosis. TEMED was used to extend the pH
      range of ampholine. Taurine was added to the ampholyte mixture to eliminate the
      aggregation of proteins. The uniform design, a new experimental design method
      suited for experiments of a large number of factors and levels, was used for the
      optimization of experimental conditions, such as concentrations of ampholine, MC
      1500, TEMED and Taurine. U6* (6(4)) table was chosen to arrange experiments.
      Regression equations of maximum current, mean migration time and criterion of
      resolution power were obtained after the treatment of experimental results by SAS
      software. Optimized experimental conditions were obtained according to
      multivariate regression equations. Carrier ampholyte which consists of 3.2%-4.8%
      ampholine 3-10, 0.06%-0.18% MC-1500, 0.8% TEMED and 1%-2% taurine will produce
      good resolution. Cathode and anode solutions were 20 mmol/L NaOH and 20 mmol/L
      HsPO4, respectively. Low pressure (34.5kPa) was applied at the inlet of the
      capillary simultaneously after 31 minutes of isoelectric focusing at 25 kV to
      mobilize the focused acidic protein zone to pass through the detector. Human
      serum albumin (HSA) and human epidermal growth factor (hEGF) were separated by
      this method using an ampholyte mixture of 4% ampholine 3-10, 0.8% TEMED, 1%
      taurine and 0.12% MC-1500. Data analysis indicated that the coefficients of
      variation of pressure and the method are all 1.2%. The results demonstrated that
      the method established is applicable to basic, neutral and acidic proteins, and
      can be used for the determination of pI by internal calibration.

PMID- 15739422
TI  - [Immunologically prepared plasma specimen of albuterol for high performance
      liquid chromatographic determination].
AB  - Immune-affinity method for preparation of sample in plasma is reported in this
      paper. Albuterol was coupled to bovine serum albumin (BSA) to prepare the antigen
      and immunized in rabbit to produce the anti-albuterol serum (immune globulin).
      The anti-albuterol serum was treated with saturated ammonium sulfate solution to
      obtain the antibody (immune globulin). The antibody was coupled with Sepharose 4B
      to prepare the immune globulin-affinity column. The plasma containing albuterol
      was introduced into the column and was rinsed in turn with phosphate buffer and
      water, and then eluted with methanol. After being concenfrated the sample was
      analyzed by HPLC with a sillica column (4.6 mm x 200 mm, 5 microm), a mixture of
      methanol: 2 mol/L ammonium acetate (99.5 : 0.5) as mobile phase with a flow rate
      of 1.2 mL/min, and fluorecence detector monitoring at lambdaex = 226 nm and
      lambdaem = 306 nm. The results showed that the immune globulin-affinity column
      has the characteristic of high purity and high specificity, and it is suitable
      for the preparation of chromatographic plasma specimen to determine albuterol in
      plasma. The relationship between peak area ratios and concentration from 2 to 80
      microg/L were linear (r=0.998). The extraction recoveries from plasma at
      concentrations of 2-80 microg/L were 98.8% +/- 7.3%. The RSD for intra-day (n=5)
      was 5.8% and that for inter-day assay (n=5) was 7.8%.

PMID- 15739423
TI  - [Preparation and characterization of sinopak-s-DEAE weak-anion exchange packing
      for high performance liquid chromatography].
AB  - High-performance ion exchange chromatography (HPIEC) is extensively used in the
      separation of peptides and proteins, especially in the biotechnology process. The
      principle of separation of proteins is based on the changes of pH and salt
      concentration in the mobile phase for the chromatographic model. A new synthetic
      method with the help of a catalyst for the bounding of diethylaminoethyl group on
      a home-made macro-pore silica sphere (the trade mark is Sinopak-s, with sphere
      size of 5 microm and pore diameter of 100 nm) was developed in our laboratory for
      the application of the scale-up separation of biotechnological target products in
      China. The Sinopak-s-DEAE weak anion ion exchange matrix for HPLC was prepared
      and characterized with various proteins. The pH value and reaction time were
      discussed for the reaction efficiency of ligand to the silica sphere. The
      coverage of the DEAE ligand on the silica surface were among 1.6 to 2.1
      micromol/m2 for six batches of packings. The influences of the pH value and the
      salt concentration in mobile phase upon the retention of proteins on the DEAE
      column were also discussed. A bio-activity recovery up to 98% for trypsin was
      arrived after purification with the DEAE column under the chosen chromatographic
      conditions. The capacity of matrix for BSA was 80 mg/g. The column was
      successfully applied to separate a mixture of several standard proteins in a
      linear gradient elution condition from 0 to 0.4 mol/L of NaCl in a 50 mmol/L of
      Tris/HCl buffer (pH 7.0) at 1.0 mL/min flow rate and detected at 280 nm
      wavelength.

PMID- 15739424
TI  - [Purification and behavior of recombinant human gamma-interferon on reversed
      phase high performance liquid chromatography].
AB  - A high performance liquid chromatographic system is described for the
      purification to homogeneity of recombinant human gamma-interferon (gamma-IFN)
      from the inclusion bodies produced in genetically transformed Escherichia Coli
      cells. Crude products of gamma-IFN obtained from typical preparative liquid
      chromatographic separation on Sephacryl S200 column was applied to analytical
      HPLC with RP-C18 column and eluted with convex gradient of 0-82% acetonitrile in
      30 min followed by linear gradient of 82%-100% in 30 min. A constant level of
      0.1% trifluoroacetic acid was maintained throughout the gradient process. The
      retention of gamma-IFN was investigated as a function of pH, temperature as well
      as concentration of salt in the mobile phase. For denatured and renatured gamma
      IFN the chromatographic profiles were analyzed under various conditions. The
      retention time of renatured gamma-IFN was compared with that of denatured gamma
      IFN and a significant difference in the retention time of profiles was observed.
      Both biological activities were reduced to different degree followed with
      incorrect disulfide bond gamma-IFN or oligomer gamma-IFN. The purified gamma-IFN
      has a specific activity about 6 x 10(6) units/mL. The eluats were assayed for
      identification of gamma-IFN using Enzyme-Linked Immunosorbent Assays (ELISA). Its
      molecular weight was 17.5 kD, as determined by SDS-PAGE. The results support that
      renatured sample with tR = 24.8 min and denatured one with tR = 30.1 min were
      identical protein with different conformation. The chromatographic behavior is
      explained by the change in net charge and polarity of gamma-IFN when the mobile
      phase condition and the conformation vary. The oligomer or incorrect disulfide
      bonds were formed during gamma-IFN renaturation and also the biological activity
      was found to be native conformation dependent.

PMID- 15739425
TI  - [Packed glass capillary column with multi-cores].
AB  - The paper describes the preparation of the columns with multi-cores and their
      plate heights, optimum gas velocity, minimum plate heights (HETP) and
      corresponding pressure drop (deltaP=Pi-Po) were measured. It is found that HETP
      increases as core number increase, but column pressure drop (deltaP) decrease
      with increase of core number. The conclusion is: 1. The column with multi-cores
      have a better permeability than the conventional packed capillary column.
      Although its column efficiency is lower than that of the conventional one when
      packed particles is in the same column size, the comprehensive properties
      (N/deltaP) are evidently superior than the conventional capillary column. 2. The
      pressure drop decreasesas the number and diameter of the core in packed capillary
      column increase. 3. When packed column particle size gets smaller, column
      efficiency gets higher, but the particle inlay bacomes difficult. The existence
      of the cores will make the column efficiency get some loss, but it can improve
      the column permeability and the inlaid geomery. 4. In considering pressure drop,
      HETP and the particle inlaid condition in column fabrication as a whole, the
      optimum column type is the packed capillary column with three cores. 5. Ideal
      column size is: deltad=1-1. 5dp,d=1-2dp,n> or =3, dp=140-250 mesh.

PMID- 15739426
TI  - A novel chiral stationary phase derived from L-proline for liquid chromatographic
      resolution of chiral compounds.
AB  - The design and preparation of a novel chiral stationary phase (CSP) were
      described. The chiral resolutions of N-3,5-dinitrobenzoyl-DL-amino acid methyl
      esters were performed on the CSP. The selectivities were between 1.04 and 1.18.
      The applications of the CSP and the optimization of the chromatographic
      conditions will be further studied.

PMID- 15739428
TI  - [LC troubleshooting-solvent life and degradation].

PMID- 15739427
TI  - [Analysis of single cells by capillary electrophoresis].
AB  - A review with 46 references is given on the application of capillary
      electrophoresis to the analysis of single cells. Injection modes, detectors and
      future prospects of this microseparation technique for single-cell analysis are
      described in detail.

PMID- 15739429
TI  - [Properties and applications of restricted access stationary phases].
AB  - Several types of restricted access stationary phases used for the analysis of
      drugs in biological fluids by direct injection into high-performance liquid
      chromatographic column are introduced in this paper with 20 references These new
      packings included internal surface reversed phase, semipermeable surface,
      shielded hydrophobic phase and mixed functional phase. The structural
      characteristics and the chromatographic properties of these packings are
      reviewed, especially with regard to their use in the assaying of drugs.

PMID- 15739430
TI  - [Structural identification of carboxylic esters by pyrolysis gas chromatography].
AB  - A pyrolysis gas chromatographic method has been investigated for structural
      identification of carboxylic esters. The method can be applied to identify not
      only pure components, but also those separated by thin layer chromatography and
      scraped from the TLC plate without removing the adsorbent. The samples were
      pyrolyzed in tube furnace pyrolyzer at 500 degrees C (conventional pyrolysis) or
      were pyrolyzed at 550 degrees C after mixing with soda-lime powder (pyrolysis
      with soda-lime). Some esters such as iso-octyl palmitate, glycerol monostearate
      and diethyl phthalate were pyrolyzed. The pyrolysis products were identified by
      comparing with the known. The parent alcohols of monohydric and polyhydric
      alcohol esters can be determined respectively according to alcohols, alkenes
      produced on pyrolysis and dehydrated products of polyhydric alcohol at high
      temperature. The parent acids of monocarboxylic esters can be determined
      according to carboxylic acid produced on conventional pyrolysis or corresponding
      alkane formed from decarboxylation of parent acids on pyrolysis with soda-lime.
      For esters formed from dicarboxylic acids that can be dehydrated to produce five
      , six-membered cyclic ketones or can be dehydrated and decarboxylated
      simultaneously to produce five-, six-membered cyclic acid anhydrides, parent
      acids can be determined according to corresponding cyclic ketones or cyclic acid
      anhydrides. This method is useful for identification of common carboxylic esters.
      When the compound or the component of the mixture was confirmed to contain ester
      group by infra-red spectroscopy, PGC or TLC-PGC can be employed to make further
      identification.

PMID- 15739431
TI  - [Analysis of the vol atiles from pigeon's excrement with capillary gas
      chromatography].
AB  - The volatiles from pigeon's excrement were obtained with a simultaneous
      distillation and extraction (SDE) equipment. The chemical composition of the
      volatiles was examined by means of capillary gas chromatography and combined gas
      chromatography-mass spectrometry. Forty seven constitutents of the volatiles were
      identified by gas chromatography-mass spectrometry. Of these compounds, thirty
      nine were further identified by measuring their temperature-programmed retention
      indexes or retention times on OV-1 and PEG-20M columns and making comparison with
      those of the corresponding authentic samples. The total compounds identified make
      57% of the total peak areas. The compound classes consist of alcohols (4),
      aldehydes (11), ketones(4), acids (8), esters (5), and phenols (2), amounting to
      43.68% of the total peak areas. The ten compounds with highest contents are,
      hexadecanoic acid (9.03%), ethyl acetate (6.85%), ethanol (4.03%), 1-ethoxy-2
      methylpropane (3.87%), acetic acid (3.23%), heptadecane-(8)-carbonic acid
      (3.20%), (Z,Z)-9,12-octadecadienoic acid (3.18%), nonanal (2.85%), 1,2
      benzenedicarboxylic, dibutyl ester (2.65%), and acetaldehyde (2.32%). Pigeon's
      excrement has long been used as a Chinese traditional medicine for the
      therapeutic treatment of haemorrhoid. Some of the constituents identified in the
      work have been reported to have antibacterial activities.

PMID- 15739432
TI  - [The determination of vitamin D in fortified milk and other foods by high
      performance liquid chromatography (HPLC)].
AB  - An HPLC procedure for determination of vitamin D(VD) in fortified milk and food
      has been developed. The samples were saponified by adding KOH, ethanol and
      vitamin C at 75 degrees C for 30 min. The digest was extracted with hexane in
      multistep manner. The extract was washed with 5% KOH, distilled water and 55%
      ethanol, and evaporated under reduced pressure at 50 degrees C. The residue was
      dissolved in hexane, transferred to a coentrifuge tube, evaporated under N2 and
      then dissolved in 200 microL mobile phase. The latter was injected into a silica
      column (10 microm, 30 cm x 4 mm) for cleanup, eluted with mixture of cyclohexane
      hexane containing 0.8% isopropanol and detected at UV 254nm. VD fraction was
      collected according to the retention time of standard, evaporized under N2,
      redissolved in 100 microL MeOH, and separated on a C18 column (10 microm, 30 cm x
      4 mm) with MeOH/H2O (98:2) as eluent. VD2 and VD3 were eluted as a mixture under
      the conditions. Recoveries of the method were 94.8% to 99.7%. The average CV (n =
      5) for within and between day measurements were 1.6% and 2.1% respectively. This
      method was already used to determine the content of vitamin D in milk powder,
      pulvis elementi compound, mixed proteins, dried meat floss, humanized milk power,
      children health drink, milk wheat powder and fortified milk. The method is
      simple, rapid and accurate.

PMID- 15739433
TI  - [Columns and separation mechanism of low pressure ion chromatography].
AB  - Ion chromatography which appeared in 1975 has been developed rapidly in recent
      years. But the working pressure increased with years. In this work, the authors
      put forward the low pressure ion chromatography (LPIC) and successfully designed
      several kinds of low pressure ion chromatography with inlet pressure of 1.92 x
      10(5)-2.94 x 10(5) Pa. Many cations, such as, alkali metals, NH4+, alkaline earth
      metals, transition metals, inorganic anions and organic acidic ions can be
      analyzed rapidly by the technique. The detectable limit of numerous ions reaches
      10(-6) g/L. Low working pressure, high performance separation and highly
      sensitive detection can be realized by LPIC. Among these, the columns play an
      important part. In this paper, the kinds and species of columns and the analytes
      are presented. The separation mechanism of low pressure ion chromatography is
      discussed, which indudes ion exchange equilibrium, complexation equilibrium and
      ion exclusion reaction. Furthermore, the relation between the exchange capacity
      of ion exchange media and the concentration of eluent are also discussed. In the
      meanwhile, the choice of LPIC elution systems and separation conditions are
      described in this paper too.

PMID- 15739434
TI  - [Design and application of vacuum manifold for solid phase extraction].
AB  - Solid phase extraction (SPE) is now a common method for sample pretreatment. SPE
      vacuum manifold is a key instrument when SPE is used for sample pretreatment. It
      was developed by National Chromatographic R. & A. Center. Being connected with a
      vacuum pump, it can deal with 12 samples simultaneously. The manifold has a
      unique rotatable cover and can be conveniently rotated when switching between any
      two steps of SPE. An application of this SPE vacuum manifold in measuring bile
      acids in human serum was given.

PMID- 15739435
TI  - [Determination of multicomponent contents in anticold solution by high
      performance liquid chromatography].
AB  - A high performance liquid chromatographic method has been successfully used to
      separate and determine the six drugs in an anticold solution. In the anticold
      solution, potassium guaiacol sulfonate, acetaminophen, D,L-methylephedrine, and
      caffeine were analyzed with a column of Zorbax ODS, by using the mobile phase of
      MeOH-0.05 mol/L KH2PO4-H3PO4 (250 : 750 : 0.5) and UV detector at 214 nm,
      dextromethorphan HBr and chlorpheniramine maleate were analyzed with the same
      column, by usingthe mobile phase of MeOH-H2O-HsPO4-SLS (80 : 20 : 0.5 : 0.2) and
      UV detector at 260 nm. This method is proved to be very effective to separate the
      six drugs mentioned above. For potassium guaiacol sulfonate, acetaminophen, D,L
      methylephedrine, caffeine, dextromethorphan HBr and chlorpheniramine, the
      response values were linear between 1.0-10 microg, 5.0-50 microg, 0.25-2.5
      microg, 0.5-5 microg, 0.25-2.5 microg, 0.05-0.5 microg respectively and the
      recoveries were 100.53% +/- 1.12%, 100.19% +/- 0.58%, 99.4% +/- 1.60%, 99.55% +/-
      1.01%, 99.37% +/- 1.52%, 99.01% +/- 1.20% (n=5) respectively.

PMID- 15739436
TI  - [Determination of taurine in Lycium barbarum L. by high performance liquid
      chromatography with OPA-urea pre-column derivatization].
AB  - Dried Lycium Barbarum L. is pretreated simply through shivering, homogenizing and
      centrifuging, and then the extract is passed through a cation-exchange column to
      exclude the interference of other amino acids. The effluent is derivatized prior
      to high performance liquid chromatographic separation on a Zorbax-C8 column. The
      derivatization reagents consist of A and B (1:9, V/V). A is 4% OPA solution in
      methanol (W/V); B is urea:sodium phosphate buffer (pH 6.8) = 1:3 (W/V). The
      mobile phase is methanol:0.01 mol/L sodium acetate (pH 6.8) = 35:65 (V/V). The
      ultraviolet-visible detector is at 330 nm. 0.1-1.0 mmol/L taurine can be
      determined quantitatively. The recovery is 100.31% +/- 1.98%. Coefficient of
      variation is 1.94%.

PMID- 15739437
TI  - [Study on reversed-phase ion-pair chromatographic determination of thiosulfate
      and iodide anions].
AB  - This paper describes an indirect reversed-phase ion-pair chromatographic
      separation and UV indirect photometric detection of and S2O3(2-) and I- by pre
      column derivatization with Hg-EDTA to form their corresponding ternary complexes
      EDTA-Hg-S2O3 and EDTA-Hg-I for the first time. On a Zorbax ODS column with a
      mobile phase of methanol-water we have studied the influences of the ion-pair
      TBA+ concentration, pH value, the addition of EDTA, the concentration of organic
      modifier and ionic strength. In our experiments, the addition of EDTA had a
      notable effect on retention and peak shape. So the best chromatographic
      conditions are: methanol:water = 23:77 (V/V), the ion-pair reagent TBA+ 3.0
      mmol/L, EDTA 1.0 mmol/L, NaNO3 2.0 mmol/L and buffer solution KH2PO4-Na2HPO4 (pH
      7.0). The eluate is monitored by a UV detector operated at 254 nm and the
      detection limits of S2O3(2-) and I- are 61.1 ng and 37.6 ng respectively. Good
      linear relationships between the peak area (Y) and the amount of anion ions (X)
      with r = 0.9851 and 0.9892, respectively, are obtained. Interference of some ions
      is also studied. The method is both convenient and selective. It has already been
      used for the determination of I- in kelp and the results are satisfactory. The
      amount of I- in kelp is 0.0183%.

PMID- 15739438
TI  - [Determination of inosine in oral tonic by high performance capillary
      electrophoresis].
AB  - This paper describes a high performance capillary electrophoresis method for the
      assay of inosine in oral tonic. The method employed a boric acid-borate buffer
      solution with SDS and UV detection at 254 nm. The capillary was 47 cm x 75 microm
      i.d.. Calibration curve shows good linearity. The recovery of inosine ranged from
      95.0%-99.8% with a coefficient of variation (CV) of 2.4% (n=4). This method is
      simple, rapid and reliable.

PMID- 15739439
TI  - [The analysis of fatty acid composition in eyes of mouse].
AB  - Fatty acids are one class of the chemical components of eyeballs, especially in
      the histological structure of retina. They are also the energy source for the
      maintenance of the normal physiology function. This paper describes the gas
      chromatographic analysis of fatty acid composition of mouse eyeballs for the
      first time. The fatty acids in mouse eyeballs were extracted by a mixture of
      chloroform-methanol-hydrochloric acid followed by esterification with methanol
      potassium hydroxide method. The separation was performed on a 25 m x 0.25 mm PEG
      20M fused silica capillary column. The qualitative and quantitative analysis of
      12 main fatty acids has been accomplished. The results indicate that the normal
      eyeballs of mouse contain high level of saturated fatty acids which were 52.8% of
      the whole fatty acids. The content of the mono-unsaturated fatty acids is
      limited, but the poly-unsaturated fatty acids are the major constituents and
      account for 18.2% of the whole fatty acids. The ratio of saturated to unsaturated
      fatty acids is 0.6.

PMID- 15739440
TI  - [Preliminary study on separation of three vitamins by capillary zone
      electrophoresis and micellar electrokinetic chromatography with amperometric
      electrochemical detection].
AB  - In this paper, separation of water soluble vitamins C (VC), B1 (VB1) and B6 (VB6)
      has been studied preliminarily by capillary zone electrophoresis (CZE) and
      micellar electrokinetic capillary chromatography (MECC) with a home-made
      amperometric electrochemical detector at the working electrode [carbon fiber (5
      microm o.d.)] potential of 510-540 mV (vs. SCE). It has been shown that each of
      the three vitamins has more than one peak in NH3-NH4Cl (pH 9.0) which were mainly
      caused by the decomposition products in weak base medium and by heat except those
      from impurities. The electrochemical detector has better performance for the
      three vitamins from CZE and MECC. They can be separated either by CZE or by MECC.
      The separation by CZE is better than that by MECC with sodium dodecyl sulfate
      (SDS). SDS and buffer acidity can influence the retention time, peak sequence and
      height. The separation efficiency of CZE in 0.01 mol/L NH3-NH4Cl was 468 800
      theoretical plates for VC.

PMID- 15739441
TI  - [Evaluation of capillary chromatographic columns packed by electrokinetic packing
      method].
AB  - In this paper, a method for electrokinetic packing capillary columns is reported.
      A higher column effeciency was obtained by performing electrochromatography on
      electrokinetic packing columns. The highest column efficiency in number of
      theoretical plate per meter was more than 200000, corresponding to reduced plate
      height less than 2. The reproducibilities of the same column in different
      intervals and different columns prepared from the same or different batches were
      compared. The relative standard deviations of the number of theoretical plate and
      retention time were less than 10% and 8%, respectively. The results indicated
      that high column efficiency and good reproducibility can be obtained on these new
      capillary packed columns.

PMID- 15739442
TI  - [The effect of alkalinity of methylation reagent on isomerization and degradation
      of polyunsaturated fatty acids with pyrolysis gas chromatography].
AB  - Simultaneous pyrolysis and methylation gas chromatography (SPM-GC) is a fast
      analytical method which was developed in recent years. However, the strong
      alkalinity of tetramethylammonium hydroxide (TMAH) may result in the
      isomerization and degradation of polyunsaturated fatty acids in oils and fats
      during analysis. This paper describes the application of SPM-GC to
      polyunsaturated fatty acids in soybean oil and the isomerization and degradation
      may be prevented by choosing the optimum proportion of TMAH to methanol which is
      1:50 (pH 8.8). With this chosen optimum proportion there were no detectable
      isomerized and degraded peaks in the chromatograms. Pyrograms were obtained by
      interfacing a Curie-point pyrolyser to a Shimadzu GC-14A gas chromatograph
      equipped with a flame ionisation detector. A capillary column (FFAP) was used.
      All of the pyrolysis products were identified by mass spectrometry which was
      carried out with a Varian 3400 gas chromatograph interfaced to a Finnigan SSQ 710
      mass spectrometer using electron impact ionisation (70 eV). This method is
      simpler and more convenient than both the methods "neutralization of acid" and
      "simultaneous injection of the sample and a short chain fatty acid methylester"
      reported in the previous papers.

PMID- 15739443
TI  - [A gas chromatographic method for determination of Butyraldehyde as a product of
      butanol biotransformation in rat liver].
AB  - Analysis of butyraldehyde obtained by the interaction of butanol with cytochrome
      P450 II E1 in rat liver microsomes prepared by centrifugation and with the NADPH
      added is described in this paper. The biotransformation rate of butanol into
      butyraldehyde can be used as an index for the assessment of the enzyme activity
      of cytochrome P450 II E1. A headspace gas chromatograghic method to determine the
      butyraldehyde has been developed. The detection limit and CV of this method for
      butyraldehyde in microsomes were 0.7 micromol/L and 8.1%-9.3% respectively. The
      recovery was 85.3%. The results show that this is a rapid and sensitive method
      with less interferences and fairly good precision. The method developed has made
      a reliable analytical methodological foundation for the assessment of the enzyme
      activity of cytochrome P450 II E1.

PMID- 15739444
TI  - [Rapid determination of allethrin, permethrin and piperonyl butoxide in
      insecticidal aerosol for household by gas chromatography].
AB  - A method of quantitative analysis for allethrin, permethrin and piperonyl
      butoxide in insecticidal aerosol for household has been studied by GC-FID. The
      gas chromatographic conditions were as follows. column:packed with 5% QF-1 on
      Chromosorb W HP, column temperature: 215 degrees C, temperature of injector and
      detector 250 degrees C and carrier gas: N2 15 mL/min. Diphenyl phthalate was used
      as the internal standard. All components and internal standard were separated in
      7 min. For allethrin, permethrin and piperonyl butoxide, the recovery were 100%,
      102% and 99.9%, and the coefficients of variation were 0.13, 0.56 and 0.48
      respectively. The method is simple, rapid and accurate.

PMID- 15739445
TI  - [Determination of changes in membrane phospholipids of rat lung and liver tissues
      from acute heat stress by high performance liquid chromatography].
AB  - The changes in the contents of phosphatidylinositol (PI), phosphatidylserine
      (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in lung and
      liver membrane tissues of rats suffered from acute heat stress were investigated
      with HPLC. The separation was performed on a mu-Porasil Si column, 300 mm x 3.9
      mm i.d., by isocratic elution of acetonitrile : methanol : 85% phosphoric acid
      (100 : 3 : 1). The phospholipids were detected at 205 nm. The results showed that
      the contents (mean +/- SD) of PI, PS, PE and PC in normal rats liver were 270.0
      +/- 18.2 microg/g, 133.7 +/- 8.6 microg/g, 1465 +/- 132 microg/g and 53.7 +/- 2.8
      mg/g respectively, whereas those in heat-stressed rats whose rectal temperature
      was increased to 42 degrees C and maintained for 15 minutes were decreased by 14%
      25% (P<0.01) except PS. When the heat-stressed rats recovered to room temperature
      for 4h, the contents of phospholipids returned to normal level. The changes of PS
      and PC in rat lung tissues were identical with those in liver tissues.

PMID- 15739446
TI  - [Quantitative determination of 7-ketocholesterol in human fetal liver cell
      supernatant and lysate by high performance liquid chromatography].
AB  - 7-Ketocholesterol (7-KC), which is a major oxidation product of cholesterol and
      is selective cytotoxic to tumour cells, was isolated from human fetal liver. A
      fast, sensitive method of high performance liquid chromatography for the
      quantitation of 7-KC has been developed and applied to the determination of 7-KC
      in human fetal liver cell suspension. In this procedure a mixture of 2 : 1
      chloroform-methanol (V/V) was used as extraction solvent. The extract was washed
      with distilled water and then evaporated to dryness under N2. An adsorption
      liquid chromatographic system used included mu-Porasil SiO2 column, hexane : iso
      propanol (91 : 9) mobile phase and UV detector at 233nm. It was found that the
      level of 7-KC in human fetal liver cell supernatant was higher than in liver
      lysate.

PMID- 15739447
TI  - [Determination of elemental sulfur in liquefied gas by high performance liquid
      chromatography].
AB  - A method for the determination of elemental sulfur in liquefied gas has been
      developed in this work. First, the elemental sulfur existed in the liquefied gas
      was extracted by chloroform and the volatile petroleum hydrocarbons vaporized
      with a rate of ca. 500mL/min at low temperature in an ice water bath. The
      elemental sulfur dissolved in chloroform was then determined by high performance
      liquid chromatography. The operating conditions were: 300 x 4mm i.d. mu-Bondapak
      C18 column; 0.8mL/min methanol-water, 95/5 (V/V), as eluent and UV-254nm
      detector. The average recovery of elemental sulfur was 98.3% and the minimum
      detectable limit was 0.1ng/g.

PMID- 15739448
TI  - [Capillary gas chromatographic analysis of micro impurities in acrylonitrile].
AB  - A megabore SCOT series column of silicone OV-101 and OV-17 for the analysis of
      micro amount of impurities in acrylonitrile is presented. By using the columns of
      50m x 0.53mm i.d. OV-101 and 25m x 0. 53mm i.d. OV-17, with column temperature of
      75 degrees C and N2 as carrier gas, u=8cm/s, the main impurities, such as
      acrolein, acetone and acetonitrile may be well separated from acrylonitrile in 26
      min. The results indicate that the series column possesses of high separation
      efficiency and long column life. The error in quantitative analysis was less than
      4%.

PMID- 15739449
TI  - [Analysis of season variation of methyleugenol and safrole in Asarum
      heterotropoides by gas chromatography].
AB  - We established a method for quantitative analysis of methyleugenol and safrole in
      Asarum heterotropoides by GC to study their season variation. The results showed
      that the content of methyleugenol in the essential oil of the subterranean part
      of different seasons was 21%-39%, and that for safrole was 17%-33%. In the
      upterranean part, methyleugenol was 1.4%-9.6%, and safrole was 0.36%-2.1%. It is
      clear that methyleugenol and safrole are provided mainly by the subterranean
      part. The quantity of methyleugenol is the richest in the period of sprouting and
      after-fruiting, and for the safrole content the richest periods are that of
      sprouting, blooming and after-fruiting. In the case of upterranean part, the
      richest time is blooming period both for methyleugenol and safrole, and after
      blooming they decrease gradually.

PMID- 15739450
TI  - [Determination of 3,5-di-t-butyltoluene by gas chromatography].
AB  - A quantitative analytical method for 3,5-di-t-butyltoluene in reaction mixture by
      gas chromatography with methyl benzoate as internal standard is reported. A
      stainless steel column of 2m x 3mm i.d. packed with 15% FFAP/Chromosorb W/AW (60
      80 mesh) and flame ionization detector were used with column temperature of 180
      degrees C and injection port and detector temperatures of 250 degrees C. There
      was a good linear calibration curve in the range from 1.1 to 9.2 microg (r =
      0.9990, n = 8). It was taken 10 minutes to complete an analysis.

PMID- 15739451
TI  - [Gas chromatographic determination of residual toluene in plastic packing bags].
AB  - A method for analysis of residual toluene in plastic packing bags by gas
      chromatographic headspace analysis is presented. This method is very simple and
      accurate. It only requires one column: 0.5 m x 2 mm i.d. packed with 102 white
      support DMCS coated with 20% PEG-20M. The relation between the preheating
      temperature of sample and the peak height of toluene can be approximately
      expressed as H=4.156e(0.126T). The precision of this method is 4% and its
      detectable limit is 0.031 mg (toluene)/m2.

PMID- 15739452
TI  - [Preparation and evaluation of a strong polar polymer capillary column].
AB  - A strong polar organic polymer porous layer open tubular capillary column, named
      OPPLOT-A column, was prepared by in situ copolymerization with the strong polar
      acrylonitrile as monomer and divinylbenzene as cross-linking agent. The polarity
      of the column is higher than that of the OPPLOT-Q, OPPLOT-R andd OPPLOT-S columns
      which prepared previously. The performance of the OPPLOT-A column was evaluated.
      It is effective to analyze alcohols, aldehydes, ketones, esters, ethers and
      nitriles etc., and especially for good separation of nitriles and aldehydes. The
      retention of the column is not influenced by water. The thermal stability of the
      OPPLOT-A column (200 degrees C) is lower than that of OPPLOT-Q (250 degrees C), 
      R (250 degrees C) and-S (210 degrees C).

PMID- 15739453
TI  - [A gas chromatographic study on the characters of adsorbents in the enrichment of
      organic compounds from air samples].
AB  - A gas chromatographic method for the measurement of enriching characters of
      adsorbents used in preconcentration of organic compounds from air samples was
      studied. The character parameters suggested in this study include adsorption
      parameters (breakthrough volume or maximum sample volume) and desorption ones
      (minimum flashing volume and the lowest desorption temperature). The parameters
      of some low-molecular-mass compounds such as alcohols, saturated hydrocarbons,
      aromatics, esters and halohydrocarbons on GDX-301 were measured by using elution
      GC method. The maximum sample volumes of all the 20 compounds (with exception of
      methanol) got from these experiments are not less than 0.8 L at 35 degrees C for
      sampling tube (filled with 2 g GDX-301) and 0.3 L at 0 degrees C for focus tube
      (with 0.14 g GDX-301). The corresponding minimum flashing volumes of less than
      177 mL and 13 mL respectively are needed to complete desorption at 180 degrees C,
      and the lowest desorption temperatures of not over 180 degrees C and 157 degrees
      C at flashing volume of 180 mL and 30 mL are lower than the maximum allowable
      operating temperature (250 degrees C) of GDX-301. The results showed that GDX-301
      is a good adsorbent for enrichment of the organic compounds mentioned above. The
      following operating conditions are recommended: using the above sampling tube and
      focus tube, actual sample volume < or = 0.8 L, adsorption temperature < or = 35
      degrees C and focus temperature 0 degrees C, desorption for 6 min from sampling
      tube and 1 min from focus tube at 180 degrees C with flashing rate 30 mL/min.
      Good correlations between the parameters and boiling point of the investigated
      compounds were found. It can be used to estimate the parameters of other organic
      compounds not measured in this study.

PMID- 15739454
TI  - [Study on the distribution and structure of polyhalides by gas chromatography
      mass spectrometry].
AB  - A series of unexpected products were obtained when 1,4-dichloro-2-butyne reacted
      with allyl bromide with the catalyst PdCl2 (PhCN)2. It is difficult to separate
      these products from each other and to identify the structure of each one due to
      their similar properties. In order to solve this problem, gas chromatography-mass
      spectrometry (GC-MS) was chosen to analyse the above products because of its good
      sensitivity and selectivity. The analytical results showed that (A) the 8
      compounds were 5,6-dichloro-4-chloromethyl-1, (E) 4-hexadiene (III), 5,6-dichloro
      4-chloromethyl-1, (Z) 4-hexadiene (IV), 5-bromo-6-chloro-4-chloromethyl-1, (E) 4
      hexadiene (V), 5-bromo-6-chloro-4-chloromethyl-1, (Z) 4-hexadiene (VI), 5-bromo-6
      chloro-4-bromomethyl-1, (E) 4-hexadiene (VII), 5-bromo-6-chloro-4-bromomethyl-1,
      (Z) 4-hexadiene (VIII), 5,6-dibromo-4-bromomethyl-1, (E) 4-hexadiene (IX) and 5,6
      dibromo-4-bromomethyl-1, (E) 4-hexadiene (X). Most compounds, except (V) and
      (VI), were the results of exchange reaction between chloride and bromide anion;
      each pair of the products are geometrical isomers. (B) in the four pairs of
      geometrical isomers, the ratio of Z-isomer/E-isomer decreased from 95:5 to 53:47
      as molecular weight increased from compounds (III) and (IV) to compounds (IX) and
      (X).

PMID- 15739455
TI  - [High performance liquid chromatographic determination of reducing sugars in
      fruit juices with laser resonance Raman detection].
AB  - A liquid chromatographic method using semi-microcolumn separation combined with
      laser resonance Raman detection was developed for the determination of
      monosaccharides in fruit juices. Reducing sugars (galactose, glucose, mannose,
      arabinose, xylose and ribose) were derivatized with 4-dimethylaminoazobenzene-4'
      sulfonyl (DABSYL) hydrazine. The derivatives of the monosaccharides exhibited
      strong resonance Raman scattering at 1136 cm(-1) when Ar+ laser emission line
      488.0 nm was used. A semi-microcolumn Inertsil ODS-2 (250 mm x 1.5 mm i.d.) was
      used to the separation of the monosaccharide derivatives. The saccharides eluted
      within 25 min. However the excess DABSYL hydrazine was retained strongly with a
      retention time of about 60 min. In order to reduce the longer analysis time, the
      excess DABSYL hydrazine was removed by adding glyoxylic acid and then Na2CO3
      aqueous solution when the derivation reaction was finished. As a result, the
      analysis time was reduced to about a half of its initial run time. The
      sensitivity of resonance Raman detection greater two orders of magnitude than
      refractive index (RI) detection. The detection limit of glucose is 10 ng (5.5
      pmol). The high selectivity of Raman detection came from the facts that only the
      interested compounds in a given sample was derived with the Raman labeling
      reagent and that only the characteristic Raman bands of the derivatives were
      selectively detected. In this work, in spite of the coexisting large quantities
      of organic acids in fruit juice, the determined values of glucose agreed well
      with those obtained by RI detection without any derivatization procedure.

PMID- 15739456
TI  - [Investigation of alpha-amylase denatured by urea and guanidine hydrochloride. I.
      Studies on denaturation mechanism and renaturation efficiency by high-performance
      hydrophobic interaction chromatography].
AB  - The varieties of alpha-amylase denatured with 8.0 mol/L urea and 7.0 mol/L
      guanidine hydrochloride (GuHCl) solutions and their refolded intermediates were
      separated and renatured through high performance hydrophobic interaction
      chromatography (HPHIC). With investigating and comparing the numbers of the
      refolded intermediates and the bioactivity recovery of renaturation by means of
      HPHIC, it was found that these are quite different. The results can be attributed
      to the different denaturation mechanism of alpha-amylase with the two denaturing
      agents. The numbers of the refolded intermediates of urea-unfolded alpha-amylase
      were found to be more than that denatured by GuHCl, because GuHCl may make the
      changes in the surface of alpha-amylase molecules, by contrast, urea may do the
      changes not only in the surface of the protein, but also in the hydrophobic
      packet interior of the molecules. The HPHIC packings with weak hydrophobicity was
      found to have good separation efficiency and to have almost continuous and many
      peaks denoting these intermediates, while that with strong hydrophobicity was
      found to have higher bioactivity recovery. The numbers of the intermediates of
      urea-unfolded alpha-amylase were much more than that of bovine pancreatic trypsin
      inhibitor (BPTI) separated by Weissman et al. The effect of temperature on the
      separations and the renaturations were investigated too. The result showed that
      the higher the column temperature, the more the refolded intermediates of
      unfolded alpha-amylase separated and the lower bioactivity recovery were obtained
      from HPHIC.

PMID- 15739457
TI  - [Separation of flavonol isomers by packed column supercritical fluids
      chromatography].
AB  - Flavonol isomers, which differ only in the position of hydroxyl group substitute
      on their chemical structures, showed different chromatographic behaviors. These
      polar compounds, in general, can be analyzed by high performance liquid
      chromatography. In this paper, the separation of flavonol isomers by home-set up
      packed column supercritical fluid chromatograph with carbon dioxide modified by
      ethanol containing 0.5% (V/V) phosphoric acid as mobile phase is described. The
      effects of temperature, pressure, composition of mobile phase and packed column
      type on the separation were studid. The addition of phosphoric acid to the mobile
      phase, which can not result in corrosion on the chromatographic system, enabled
      flavonol to elute from the column, and showed that the composition of the mobile
      phase was the most pronounced factor influencing the separation. Three columns
      were evaluated for the separation. It showed that the phenyl-bonded silica column
      was the best and the ODS column was the worst for the isomers separation.
      Increasing pressure shortened the retention time of each compound with good
      resolution, and higher temperature led to longer retention time.

PMID- 15739458
TI  - Immobilized IDA-type Cu2+-chelating membrane affinity chromatography for
      purification of bovine liver catalase.
AB  - Cu2+-chelating membrane medium based on iminodiacetate-substituted modified short
      cotton cellulose was examined to purify bovine liver catalase (BLC) by affinity
      chromatography. The buffer pH notably affect BLC binding to the Cu2+-chelating
      membrane adsorbent. The results showed that under the chromatographic conditions
      chosen, 67.7% recovery of BLC attained with an overall 4.7-fold increase in
      specific activity in a single step. After purification of BLC, the chelating
      membrane adsorbent can easily be regenerated by imidazole or EDTA buffer.
      Different results were obtained by the two regeneration methods: the later is
      more effective than the former in reviving the purification characters of the
      chelating membrane adsorbent.

PMID- 15739459
TI  - [New advances in liquid chromatography-chemiluminescence detection].
AB  - A review on the new development of chemiluminescence (CL) detection for liquid
      chromatography (LC) is presented. It covers CL detection systems (including
      luminol, peroxyoxalates, and other chemiluminescence reactions) combined with LC,
      the design of CL detectors, analytical methods for many kinds of inorganic,
      organic and biologic samples, applications and the trends of LC-CL in
      environmental, biomedical, life science and pharmaceutical analysis.

PMID- 15739460
TI  - [DNA polymorphism analysis by capillary electrophoresis].
AB  - A review is given here to describe the principle and methods of gene polymorphism
      analysis by capillary electrophoresis (CE). DNA length polymorphism and sequence
      polymorphism are very important phenomena in gene molecular biology. Some
      practical works of gene length polymorphism analysis and sequence polymorphism
      analysis are listed. SSCP and HPA methods detecting gene point mutations are
      demonstrated. Applications of gene polymorphism analysis by CE in clinical,
      forensic and biological research are also discussed in this paper.

PMID- 15739461
TI  - [Lecture of principles and applications of capillary electrophoresis (IV)
      Applications of CE in amino acids, peptides and protein analysis].

PMID- 15739462
TI  - [Discussion of the validation of thin-layer chromatographic procedure in
      pharmaceutical analysis].
AB  - TLC has become a convenient, fast, robust, and cost efficient technique in
      pharmaceutical analysis because of its coherent features. The important
      analytical performance parameters are summarized, such as accuracy, precision,
      reproducibility, specificity, detection limit, quantitation limit, linearity and
      range, etc. The validation methods and the acceptance criteria are discussed for
      sample preparation, sample stability in solution and on plate, sample exposure
      time, robustness and quality of stationary and mobile phases, application of
      sample to plate, spot dimension and shape, temperature, humidity and chamber
      saturation, detection, and quantitation, etc. It is recommended that the
      definition of the validation parameters and the validation procedures for
      quantitative TLC should be described whenever the results are reported.

PMID- 15739463
TI  - [Empirical expressions for the chromatographic peak width at inflection points
      and base].
AB  - From EMG function and linear regression, the projective distances on abscissa
      between inflection points in the left side (TL) or in the right side (TR) and the
      apex of a chromatographic peak which the asymmetry at 0.1 height fraction is
      within 1.09-3.00 can be expressed as: TL = -0.7898 + 0.8219 W(0.1,L), TR =
      0.03536 + 0.4582 W(0.1,L), where W(0.1,L) is the projective distance on abscissa
      between the point at 1/10 height fraction in the left side and the apex. The
      correlation coefficients are all over 0.998 and the relative error limits are
      within -0.65%-0.40% and -0.39%-0.67%, respectively. The relationship between the
      peak width at base Wb and the peak width at half height W(0.5) or the peak width
      at 1/10 height fraction W(0.1) can be expressed as: Wb = 0.04827 + 1.6907 W(0.5),
      Wb = 1.9066 + 0.5300 W(0.1). The correlation coefficients are all over 0.999 and
      the relative error limits are within -0.54%-0.69% and -1.05%-1.40%, respectively.

PMID- 15739464
TI  - [Chiral separation of racemic 5-(p-hydroxyphenyl)-5-phenylhydantoin by RP-HPLC
      using eluents containing beta-cyclodextrin].
AB  - A chiral RP-HPLC method was developed to assay the 5-(p-hydroxyphenyl)-5
      Phenylhydantoin (p-HPPH) enantiomers, the major metabolite of antiepileptic drug
      phenytoin, in rat hepatic microsomes. A 50 mm FLC-C8 column was used as the
      analytical column, beta-cyclodextrin (beta-CD) as chiral mobile phase additive
      and phenobarbital as the internal standard. The detection wavelength was 250 nm.
      The linear range of p-HPPH enantiomers was 0.5-110 mg/L. The detection limit was
      5 ng (S/N = 3). The recoveries of S- and R-p-HPPH were 93.6% +/- 2.8% and 94.7%
      +/- 1.8% respectively. The RSD within day and between days were less than 2%. The
      concentration of beta-CD played an important role in separating chiral
      enantiomers. When the concentration of beta-CD was between 8.8 and 13.2 mmol/L
      the resolution of p-HPPH enantiomers had the largest value Rs = -1.1. In this
      work, 8.8 mmol/L beta-CD solution (4 g beta-CD, 6 g urea, and 1.5 g ammonium
      acetate in 400 mL water) was selected in considering some factors such as column
      efficiency, solubility of beta-CD etc. Urea can increase the solubility of beta
      CD. When urea: beta-CD = 1:1-1.5:1 (g/g), the solubilization of beta-CD was
      significant. Methanol concentration in mobile phase affected retention time,
      resolution of p-HPPH enantiomers and solubility of beta-CD.

PMID- 15739466
TI  - [The spectrum analysis of high performance liquid chromatographic peak by
      ultraviolet-visible spectrophotometric detectors].
AB  - In the analysis of high performance liquid chromatography (HPLC), the
      qualification of chromatographic peak can be carried out by the methods of adding
      standard, comparing retention time and absorption spectrum etc. This paper
      reports a simple and practical method for measurement of absorption spectrum of
      HPLC peak by ultraviolet and visible variable wavelength detector. A BASIC
      program was edited with Shimadzu C-R4A data processor. Stopping the pump at the
      retention time we use the program to analyse absorption spectrum of the peak and
      the absorption spectrum of standard (Cr, PU, UA) by Shimadzu UV-2201 UV-VIS
      recording spectrophotometer and the absorption spectrum of standard (-S) with
      sample (-T) by this method are presented. The figure shows that the absorption
      spectra of the samples of Cr, PU and UA almost completely overlapped with those
      of the standards. The results showed that this method is reliable.

PMID- 15739465
TI  - [Determination of amino acids by precolumn derivatization with o-phthaldialdehyde
      (OPA) and reversed-phase high performance liquid chromatography].
AB  - A manual pre-column derivatization procedure has been developed for the
      determination of amino acids in sample by reversed-phase high performance liquid
      chromatography. OPA/3-mercaptopropionic acid (3-MPA) were used as derivatization
      reagents and separation of OPA-amino acids derivatives was performed on a 5
      microm partical-size ODS column. A phosphate buffer of 10 mmol/L pH 7.2 (PB)
      containing 0.3% tetrahydrofuran (THF) was used as mobile phase (A) and a mixture
      of PB-methanol-acetonitrile (50:35:15) as mobile phase (B). A single linear
      gradient program was employed and the signals were detected at 340 nm with UV
      detector. Under the above conditions all 18 amino acids in standard solution were
      separated to baseline in 40 minutes. The precision of analysis was observed from
      the reproducibility of the retention times and peak areas of eight consecutive
      injections of 18 amino acids standard solution and the results showed that both
      retention times and peak areas were highly reproduceable with the RSD 0.09%-0.48%
      for retention times and 1.2%-4.9% for peak areas. The linearity of UV response
      was tested by injecting of derivatized amino acid with different concentrations
      from 25 to 250 micromol/L for each of 18 amino acids. The r values were 0.996
      0.999. External standardization method was used for the quantitation. The method
      was applied to analyze amino acid composition of bovine serum albumin (BSA) and
      the results were in consistence with literature values. Free amino acids in rat
      plasma were also determined and good results were obtained.

PMID- 15739467
TI  - [Studies on determination of p-aminophenol and its related compounds prepared
      with catalytic hydrogenation by reversed-phase high performance liquid
      chromatography].
AB  - Catalytic hydrogenation of nitrobenzene with supported palladium catalyst is a
      new method to produce p-aminophenol. p-Aminophenol, aniline and 4,4'
      diaminodiphenyl ether obtained from this method were determined by reversed phase
      high performance liquid chromatography. The factors, e.g., concentration of
      methanol, pH and ionic strength which could affect separation efficiency were
      studied. UV spectra of p-aminophenol, aniline and 4,4'-diaminodiphenyl ether were
      recorded. Good separation was performed by using a 100 mm x 4.6 mm column with 5
      microm Hypersil ODS, a mixture of 60% aqueous 8.0 mmol/L KH2PO4 buffered to 6.5
      with 4.0 mmol/L Na2HPO4 and 40% methanol as mobile phase at a flow rate of 1.0
      mL/min, and UV spectrophotometric detector at 232 nm wavelength. The calibration
      curves of p-aminophenol, aniline and 4,4'-diaminodiphenyl ether have good
      linearity over concentration range of 5-250, 5-150 and 0.2-120 mg/L,
      respectively. Minimum detectable limits at a signal-to-noise ratio of 2 were 0.1,
      0.6 and 0.6 ng. This method has been applied to analysis of the reaction products
      of ultrasonic catalytic hydrogenation and industrial samples with good results
      and reproducibility.

PMID- 15739468
TI  - [Determination of furanoterpenoid toxins from sweet potato by thin-layer
      chromatography].
AB  - Sweet potato root tissue, when infected with different pathogens, invaded by
      insects, or irritated by certain chemicals, turns black-brown and produces and
      accumulates a large amount of furanoterpenoids such as ipomeamarone,
      ipomeamaronol, ipomeanine and 4-ipomeanol, which are toxic to animals. The
      furanoterpenoids from sweet potato root tissues infected with Ceratocystis
      fimbriata were extracted with ether. The extract solution was washed with 5%
      Na2CO3 and followed with distilled water and dried with dehydrated sodium sulfate
      (Na2SO4). The resulting ether extract was evaporated and the residue (crude
      sample) was dissolved in a small volume of chloroform. The determination of
      furanoterpenoid toxins was made on the plates at 20 degrees C and 30 degrees C
      respectively. The chloroform-soluble fraction was spotted on a silica gel G thin
      layer plate and developed using different solvent systems, n-hexane and
      ethylacetate (4:1, V/V) , benzene and methanol (9:1, V/V) and petroleum ether and
      ethylacetate (2:1, V/V), until the solvent front migrated 10 cm from the starting
      spots. After development, Ehrlich's reagent was sprayed on the plate to detect
      the compounds. In the experiment, pure ipomeamarone and ipomeamaronol were used
      as standards. Thin-layer chromatograms on silica gel plates showed the
      furanoterpenoids were resolved effectively. The repeatability of Rf value was
      good. The resolution was the best in the solvent systems of benzene-methanol and
      petroleum ether-ethylacetate at 20 degrees C. After spraying Ehrlich's reagent,
      ipomeamarone (C) appeared as a light pink spot which soon changed to a dark gray,
      ipomeamaronol (A) as a purple red spot, compound B and D as a purple red and a
      gray spot respectively. Compound A, B, C and D had Rf values of 0.05, 0.14, 0.55
      and 0.64 (n-hexane-ethylacetate), of 0.15, 0.29, 0.61 and 0.71 (petroleum ether
      ethylacetate), of 0.40, 0.55, 0.71 and 0.79 (benzene-methanol), respectively. The
      separated spots were scanned by CS-930 TLC scanner at 527 nm and quantitative
      determination by external standard calibration. Ipomeamarone was detected by thin
      layer chromatography and the limits of detection were 0.005 microg for pure and
      0.02 microg for crude sample.

PMID- 15739469
TI  - [Selection of TLC solvent system for separating substituted ferrocyclopentadienyl
      borane using orthogonal array method].
AB  - A series of substituted ferro-cyclopentadienyl borane compounds were separated by
      using thin-layer chromatographic technique. The optimum mobile phase was acetone
      cyclohexane-tetraethyl ammonium halide (0.59:8.24:1.18). The orthogonal array
      method was used to get the optimum chromatographic condition. The types and the
      concentrations of different kinds of ion-pair reagents, the contents of acetone
      and cyclohexane were considered as factors which affected the results of
      separation. The operating conditions for each experiment was adopted based on the
      L9 (3(4)) design. A statistical method of variance analysis was used to evaluate
      the overall degree of separation (D(S)), a criterion which reflects the degree of
      optimization. As a result, we found the most important factors that affected the
      separation and the optimum chromatographic condition for 8 compounds of this
      sort.

PMID- 15739470
TI  - [Determination of organic acids and inorganic anions by gradient ion
      chromatography].
AB  - The chromatographic conditions for separation and detection of organic acids and
      inorganic anions by gradient ion chromatography with suppressed conductivity
      detection were studied. The optimized gradient programs were established. Ion
      chromatography were performed with a DX-100 chromatograph (DIONEX). The
      separation column is IonPac-AS11. Compared with NaHCO3/Na2CO3 and Na2B4O7, NaOH
      was the optimal eluent. The effect of organic modifier was also studied. Among
      methanol, 2-propanol and acetonitrile, methanol can make ion pairs such as malate
      and succinate, malonate and tartrate gaining baseline resolution. By using ion
      exchange separation, Cl-, NO3-, malate, succinate, malonate, tartrate, SO4(2-),
      oxalate were eluted between 5 mmol/L NaOH-16% CH3OH and 10 mmol/L NaOH-16% CH3OH
      in 25 min. A mobile phase composed of 30 mmol/L NaOH, 50% CH3OH and D.I. water
      was chosen to elute two groups of organic acids and inorganic anions: (1)
      quinate, formate, Cl-, malate, malonate, oxalate, citrate, isocitrate, aconitate;
      (2) lactate, Cl-, SO4(2-), tartrate, PO4(3-), citrate, isocitrate, aconitate. The
      detection limits (S/N = 3) were 0.1625 (quinate), 0.0691 (formate), 0.0115 (Cl-),
      0.0886 (malate), 0.0591 (malonate), 0.0263 (oxalate), 0.1147 (citrate), 0.2017
      (isocitrate), 0.3656 (cis-aconitate), 0.1045 (trans-aconitate), 0.1950 (lactate),
      0.0729 (tartrate), 0.0224 (SO4(2-)) and 0.0692 (PO4(3-)) mg/L. The relative
      standard deviations were lower than 11.9% (n = 7) and the correlation
      coefficients ranged from 0.9212 for Cl- to 0.9999 for formate. The method was
      applied to determine the organic acids and inorganic anions of beverages and
      citric acids fermenting-medium. The results were satisfactory.

PMID- 15739471
TI  - [Elution behaviors of cations on the serial columns combining a cation exchange
      column with an ion exclusion column].
AB  - The elution behaviors of cations (Na+, NH4+, K+, Ca2+ and Mg2+) on the serially
      connected cation exchange column (ICS-C25) and ion exclusion column (TSKgel OApak
      A) were investigated. As shown in Figure 1, three peaks were observed for each
      cation when a mixture of tartaric acid (TA) and 2,6-pyridinedicarboxylic acid
      (PDC) was used as eluent. In ion exchange chromatography, the background
      conductivity (G0) of carboxylic acid (HR) eluent which is based on the
      dissociation of HR, can be expressed as follows: G0 = C0H lambdaH + C0R lambdaR
      (1) where C0H and C0R are the initial concentration, lambdaH and lambdaR are the
      equivalent concentration of H+ and R-, respectively. The concentration of eluent
      anion R- in mobile phase is reduced when the cations (M) are eluted from cation
      exchange column, because the R- forms some complexes with the cations. At this
      time, the conductivity (G) of the eluent will be G = CM lambdaM + (C0R - C'R)
      lambdaR + (C0H - CM) lambdaH (2) where CM is the concentration of cations, and
      C'R is a reduce of R-. The peaks on chromatogram results from a change in
      conductance (deltaG), and in the conditions of the paper. DeltaG = G - G0 = CM
      (lambdaM - lambdaH) - C'TA lambdaTA - C'PDC lambdaPDC (3). On the ion exclusion
      column, the eluent anion TA and PDC were retained at different capacity factor by
      an ion exclusion mechanism while the cations have not any retention. That is to
      say, the first peak of each cation is caused by elution of the cation and the
      depletion of eluent ion (H+) in the mobile phase. The second and third peaks have
      appeared corresponding to the depletion of TA and PDC anion in mobile phase,
      respectively.

PMID- 15739472
TI  - [The analysis of C4 and C5 olefins in cracking gasoline].
AB  - The paper described the analytical method of butenes and pentenes in cracking
      gasoline with a boiling point range from initial to 210 degrees C. Beside the C3
      (propane + protene) and n, i-C4 = (n-butene + i-butene) combine peaks, all C2-C5
      components in the sample were separated on the OV-1 column. The proportion of the
      combined peaks was determined on the Al2O3 column. The quantitative results were
      calculated on the data determined from the above one-column analytical systems
      with a relative standard deviation < 8%. Comparing with the ASTM D2427-87, the
      simple operation, easy application, good repetition and all component results
      were characteristic of the method.

PMID- 15739473
TI  - [Study on chemical constituents of essential oil of Vitexd rotundifolia L. by gas
      chromatography/mass spectrometry].
AB  - The essential oil of the Vitexd rotundifolia L. was abstracted by steam
      distillation. The oil obtained was dried with anhydrous sodium sulfate. The
      chemical constituents were analyzed by GC/MS. More than 30 peaks were separated
      by GC, and 28 compounds were identified by using NBS mass spectral data, and the
      Wiley/NBS registry of mass spectral data. The structrure of delta3-carene was
      further verified by GC/FTIR. The identified constituents represent over 95% of
      the peak area on TIC of the essential oil. The major chemical constituents of
      them are delta3-carene, 1,8-cineole, sabinene, beta-phellandrene and
      isoterpinolene.

PMID- 15739474
TI  - [Determination of liensinine in plasma by high performance liquid
      chromatography].
AB  - A sensitive method of high performance liquid chromatography (HPLC) for
      determination of liensinine in plasma is reported. An Ultrasphere Si column, 250
      mm x 4.6 mm i.d. with dichloromethaneisopropyl alcohol-diethylamine (75:25:0.2,
      V/V) as mobile phase at a flow-rate of 1.0 mL/min and UV-detector at 282 nm were
      used. Neferine was served as the internal standard. Liensinine in plasma was
      extracted with diethyl ether three times after adding ammonia-ammonium chloride
      buffer (pH 10). Liensinine was completely separated from nefrine. The retention
      times of liensinine and neferine were 8.5 and 5.0 minutes, respectively. The
      calibration line of liensinine was linear in the range of 0.0625-5.0 mg/L (r =
      0.9996). The mean recovery was 93.6% with RSD of 1.9%. The precision of intra-day
      and inter-day for liensinine was in the range of 1.4%-4.1% and the detectable
      limit was 0.025 mg/L based on a signal-to-noise ratio of 3. The results showed
      that the method was simple and sensitive.

PMID- 15739475
TI  - [Determination of pseudouridine in serum by high performance liquid
      chromatography].
AB  - Pseudouridine is a modified nucleoside derived from the degradation of transfer
      ribonucleic acid. The elevation of modified nucleosides in urine has been
      suggested to be caused by higher turnover rate of t-RNA in tumor tissue than in
      healthy tissue, rather than by cell death. A method of pseudouridine
      determination in serum was developed by high-performance liquid chromatography on
      a Nova-Pak column (Waters) with 0.04 mol/L KH2PO4 (pH 4.0) as mobile phase. The
      blood samples were collected and 0.6 mL of serum was treated with 0.4 mL 6%
      HClO4. The precipitate was centrifuged for 10 min at 3000 r/min. Five-hundred
      microL of the liquor was dried by air-stream at 60 degrees C. The residue was
      dissolved with 300 microL mobile phase and 10 microL was injected. The average
      recovery was 93.50 +/- 2.1%. The calibration curve was linear within the
      concentration range of 0.7-6.8 micromol/L. The serum pseudouridine concentrations
      for patients with hepatitis, lung cancer, nephritis and uremia were determined
      and those of patients with lung cancer and uremia were found significantly higher
      than those of healthy controls (p<0.05). And for patients treated with He-Ne
      laser no significant change of the pseudouridine hasn't been found (p<0.05).

PMID- 15739476
TI  - [Studies on the packings of high performance strong cation exchange
      chromatography for the separation of proteins].
AB  - In this paper, the studies on the synthesis, chromatographic characteristics and
      application of new packings of high performance strong cation exchange
      chromatography with sulfonic group for the separation of proteins have been
      reported. The silica with the end hydroxyl group reacted with chlorosulfonic acid
      and thus packings for high performance strong cation exchange chromatography were
      obtained. The recovery of bioactivity for lysozyme of these high resolution
      packings is over 76%. The packings can be used for the separation of proteins and
      biotechnological products.

PMID- 15739477
TI  - [Determination of decomposition products of di-t-butyl peroxide by gas
      chromatography].
AB  - In this work we found that there were five decomposition products of di-t-butyl
      peroxide at 320 degrees C by GC-MS. The peak area of acetone as a chief product
      in the thermal decomposition was related to di-t-butyl peroxide concentration in
      a linear manner. The range was from 22.91 to 114.93 microg (r=0.9997, n=4). By
      use of the calibration, we can possibly determine the content of the peroxide
      rapidly. The present method is more suitable for the determination of peroxide
      that is liable to decompose and difficult to be vaporized.

PMID- 15739479
TI  - [Reversed-phase high performance liquid chromatographic determination of propofol
      in human plasma].
AB  - An RP-HPLC method is described for the assay of propofol (2,6-diisopropylphenol),
      a new anesthesia drug, in human plasma. Protein in sample was precipitated with
      methanol, followed by extraction of propofol with cyclohexane. Both propofol and
      the internal standard thymol were derivatized with Gibbs' reagent and then
      chromatographed on an ODS column (Ultrasphere, 250 mm x 4.6 mm i.d.) with a
      mobile phase of acetonitrile-water-trifluoroacetic acid (80:20:0.1) and UV
      detection at 276 nm. The detectable limit of propofol was 24.8 microg/L (S/N>2)
      and calibration curves were linear between 50 to 1500 microg/L (r=0.9991). The
      average coefficient of variation was 6.1%.

PMID- 15739478
TI  - [Rapid determination of low molecular weight aldehydes in air by gas
      chromatography].
AB  - This paper reports a method for determination of low molecular weight aldehydes
      in polluted air by GC-FID using a GDX-401 packed column (3 mm x 3 m). The
      advantages of this method are simple, rapid, accurate and sensitive. The method
      requires only 8 minutes for the whole analysis. In the concentration range of 1.7
      442.4 mg/m3 for formaldehyde and 0.5-680 mg/m3 for acetaldehyde and
      propionaldehyde the calibration curves are linear. The minimun detectable amounts
      are 3.5 ng, 1 ng and 1 ng, and the average recoveries (n=5) are 89.4%, 89.6%,
      88.1% for formaldehyde, acetaldehyde and propionaldehyde respectively. The
      quantitative determination is performed by external standard calibration method.
      The results of sample analysis are satisfactory.

PMID- 15739480
TI  - [Peak shape distribution rule of high performance liquid chromatography in the
      end of column under linear and nonideal conditions].
AB  - The central moments of chromatographic elution curve are important parameters for
      describing the column efficiency and chromatographic peak shape. According to the
      equation of chromatographic dynamics, we can get the second central moment and
      the third central moment of elution curve of HPLC under linear nonideal
      conditions. In our work, we investigated the relationships between second central
      moment, third central moment, coefficient of skewness of components distribution
      in the end of column and chromatographic column parameters, operation conditions,
      such as diameter of packing particle, desorption constant, diffusion coefficient
      in mobile phase, linear velocity of mobile phase, effect of extra column and so
      on. By means of computer, we discovered that there are no significant differences
      the second central moment, third central moment and coefficient of skewness for
      different components with different distribution coefficients. In the column end,
      therefore, different components have similar peak shape if there exist no obvious
      extra column effects. The column extra effect which stems from joint line and/or
      dead volume of detector is an important factor, causing column efficiency lower
      and peak shape tailing.

PMID- 15739481
TI  - [Determination of minor flavor components in Chinese spirits by direct-injection
      technique with capillary columns].
AB  - Chinese spirits are among the best-known distilled alcoholic beverages in the
      world. Because of the longer multiple-strain fermentation, Chinese spirits are
      richer than yeast fermented western liquors in fragrance and mellow. The complex
      nature of Chinese spirits often makes it difficult to separate, identify and
      quantify major and minor flavor components. Among the several analytical methods
      for flavor components in Chinese spirits developed in recent years, the direct
      injection technique using capillary columns is by far the best. In this study of
      direct injection with crosslinked PEG 20M, HP-INNOWax and bonded SGE BP21
      columns, up to 68 flavor components including alcohols, organic acids, esters,
      acetals, carbonyl and heterocyclic compounds were identified with fine-tuning
      separation and followed by GC/MS to identify. The gas chromatographic separation
      of flavour components of Maotai Liquor by the method on PEG 20M, SGE BP21 and HP
      INNOWax are shown. The compounds of the numbered peaks in the chromatograms are
      listed. Three compounds of, ie., amyl acetate, t-pentanol and 2-ethyl butyric
      acid, were used as internal standards to minimize discrimination in quantitative
      determination. The operation procedures for these tests were provided. The
      application identities of three capillary columns for the analysis of minor
      flavor components with direct injection were summarized respectively.

PMID- 15739482
TI  - [The study of relation of the retention indices of n-alkenes with their molecular
      structure].
AB  - When the difference values between the retention indices of homologous series of
      n-alkenes and that of n-alkanes with the same carbon number were plotted with the
      number of carbon atoms in the molecule, it can be seen that the curve is nearly
      an exponential curve. We proposed an accurate formula to predict the retention
      indices of homologous series of n-alkenes. The retention indices of a total of 99
      C12-C16 n-alkenes on capillary columns with stationary phase of Squalane, PFE and
      PEG-4000 were calculated. The standard deviations of the retention indices were
      +/-0.9-+/-1.5 index units. When the retention indices of n-alkenes with the same
      carbon numbers and the same geometric structure were plotted with the positions
      of the double bond in the molecule, it can be seen that the curve is also
      approximately an exponential curve. Therefore, we put forward an exact formula to
      predict the retention indices of the n-alkenes. The universality of the formula
      is demonstrated by predicting a total of 178 retention indices of C15-C18 n
      alkenes on capillary columns with stationary phases of C87 hydrocarbon, Apiezonl
      L, CW-20M. The standard deviations of retention indices were +/-0.9-+/-1.2 index
      units.

PMID- 15739483
TI  - [Separation of drugs cephalexin, ampicillin, and their biosynthetic precursors L
      Phe-L-Cys-D-Val and D-Phe-L-Cys-D-Val by capillary zone electrophoresis].
AB  - The separation of drugs cephalexin, ampicillin and their biosynthetic precursors
      L-Phe-L-Cys-D-Val and D-Phe-L-Cys-D-Val was investigated by using capillary zone
      electrophoresis in acidic Tris-H3PO4 buffer at pH 2.3. With 50 mmol/L Tris-H3PO4
      (pH 2.3) buffer, L-Phe-L-Cys-D-Val and D-Phe-L-Cys-D-Val were only partially
      separated whereas near baseline separation was achieved between cephalexin and
      ampicillin. The experiments showed that the addition of beta-type cyclodextrins
      (beta-CD) to the running buffer can influence the separation selectivity. When
      beta-CD was used as buffer additives at 12 mmol/L, the separation between L-Phe-L
      Cys-D-Val and D-Phe-L-Cys-D-Val was much improved, however, the separation
      between cephalexin and ampicillin was impaired. When using 50 mmol/L Tris-H3PO4
      containing 12 mmol/L DM-beta-CD (pH 2.3) buffer system, all compounds
      investigated were completely separated. This separation method is simple, fast
      and easy to operate. It involves only the conventional reagents with a much lower
      run cost than using HPLC. It is expected to be used in the synthetic process
      monitoring.

PMID- 15739484
TI  - [A research on the determination of trace secondary amines by reversed-phase high
      performance liquid chromatography with electrochemical detection].
AB  - A new sensitive method for determination of ultratrace secondary amines has been
      described. It is the first time to use dansyl chloride as electrochemical
      derivatization reagent for secondary amines. The optimum experimental conditions
      have been established. At first, trace secondary amines were derivatised with
      dansyl chloride at 40 degrees C for 30 minutes, then the mixture was injected and
      separated on a Perkin-Elmer/HS-3 C18 (83 mm x 4.6 mm i.d. 3 microm) column with
      methanol aqueous solution (70/30, pH 3.3) which contained 20 mmol/L potassium
      biphthalate buffer as mobile phase and detected with electrochemical detection at
      E = +1.1 V (Ag/AgCl). The calibration curves were linear in the range of 0.225-54
      pg for dimethylamine; 1.1-264 pg for diethylamine, 0.43-102 pg for piperidine.
      The detection limits were 0.024, 0.60, 0.090 pg respectively and the coefficients
      of variation were less than 3.5% (n = 7).

PMID- 15739486
TI  - [Theory of column performance and application of capillary
      electrochromatography].
AB  - 56 papers are reviewed in this article showing the development of the column
      preparing techniques and the advances of the application of capillary
      electrochromatography (CEC).

PMID- 15739485
TI  - [Studies on the performance and applications of chloropropyl bonded silica. I.
      Separation of disubstituted benzene isomers and prostaglandin epimers].
AB  - The performance of chloropropyl bonded silica (CPS) in HPLC and its applications
      in separation of disubstituted benzene isomers and prostaglandin epimers were
      studied. The CPS column has high column efficiency and the kinetic curves
      illustrate it is suitable for fast analysis. The effect of composition and pH
      value of mobile phase (methanol/water or methanol/20 mmol/L H3PO4-NaOH buffer) on
      the retention of the solutes were investigated. Generally, the main retention
      mechanism of solutes was hydrophobic interaction, however there also exited polar
      adsorption interaction, ion-dipole interaction etc. When the mobile phase
      condition changed, the main separating mechanism may be changed with CPS column.
      So, with increasing pH value of mobile phase, the retention of isomers of
      nitrophenol exhibited a parabolic change. The chromatographic condition was
      optimized, and the isomers of nitrophenol, aminophenol and toluidine etc. as well
      as the epimers of 15-methyl-PGF2alpha were separated very well on the column.
      Moreover, the speed of separation was faster than that in general reversed-phase
      system. CPS showed to have good stability to heat and solvent and it was also a
      very stable intermediate to prepare bonded phase with various functional groups.

PMID- 15739487
TI  - [Review of the development of capillary electrochromatography].
AB  - Capillary electrochromatography is a new micro-LC technique which combines the
      selectivity of HPLC and the high efficiency of HPCE. It utilizes EOF or EOF with
      pumped flow to drive mobile phase fluids through a stationary phase in a
      capillary column and permits the separations of charged and uncharged compounds.
      Capillary electrochromatography can be divided into three categories: packed
      column electrochromatography, open-tubular electrochromatography and pressurized
      flow electrochromatography. The paper surveys the recent development of the
      capillary electrochromatography.

PMID- 15739488
TI  - [Studies on the chemical constituents of the alga Sargassum carpophyllum J.
      Agardh].
AB  - The alga Sargassum carpophyllum J. Agardh collected from the South China Sea was
      immersed in 95% ethyl alcohol. The combined extract was partitioned between ethyl
      acetate and water. The ethyl acetate phase was subjected to pressure-reduced
      chromatography over Silica H, eluted with a step gradient of EtOAc in petroleum
      ether. Two main fractions of sterols (I) and fatty acids (II) were obtained. The
      composition of I and II were identified by GC/MS. The fraction Ia was obtained,
      as a main composition of I, by repeated flash chromatography. On the basis of
      spectroscopic analysis, Ia was identified to be fucosterol.

PMID- 15739489
TI  - [Capillary isoelectric focusing method and its applications].
AB  - Capillary isoelectric focusing (CIEF) is reviewed in this article with 64
      references. Separation mechanism, manipulation of electroosmosis, mobilization
      methods, detectors and some problems associated with the determination of samples
      are discussed. Different methods for performing CIEF are evaluated. Non-cross
      linked polyacrylamide coated capillary is recommended. As for untreated column,
      dynamical coating with cellulose polymers allows a residual electroosmotic flow
      to carry the focused zone to pass through the detector. Some applications, such
      as separation of transferrin isoform, human Hb variants, t-PA glycoform, are
      presented.

PMID- 15739490
TI  - [Separation of alpha-amino acids and peptides by chelated metal ion affinity
      chromatography].
AB  - The hydrolytic solution of proteins mainly contains free amino acids and
      peptides. The separation of amino acids and di- and tri-peptides is very
      significant and also a complicated work. This report presents a chelated metal
      ion affinity chromatographic (CMAC) method for the separation of alpha-amino
      acids and peptides. Sephadex G10 was used as the solid matrix. It was epoxy
      activated by epichlorophydrin; then coupled with iminodiacetate (IDA) and
      chelated with copper ion to produce immobilized copper-ion affinity
      chromatographic packing. Some examples are given for the chromatography of model
      mixtures of L-Val, L-His, L-Tyr, L-Try, Tyr-Try dipeptides and protein
      hydrolyzing solution of fish. The separation was based on the different
      stabilities of copper complexes of alpha-amino acids, peptides and IDA-Sephadex
      G10. The components which form weak complexes with copper apparently move along
      with the solvent front. Alpha-amino acids-copper complexes with a stability
      comparable to that of copper-IDA-Sephadex G10 are retained on the matrix.
      Peptides form strong complexes and catch copper from the matrix. They are only
      slightly retained. The results showed that alpha-amino acids and peptides were
      completely separated under the experimental conditions.

PMID- 15739491
TI  - [Determination of R- and S-mephenytoin in human urine by gas chromatography].
AB  - The levels of R- and S-mephenytoin in human urine were determined by chiral
      capillary gas chromatography with nitrogen-phosphorus detector. The conditions of
      the chromatography and detection included a chiral capillary column (Chirasil
      Val, 25 m x 0.25 mm i.d., Alltech), column temperature (T) 190 degrees C,
      injector T 220 degrees C, detector T 240 degrees C, and the flow-rates of 0.85,
      3.5 and 120 mL/min for nitrogen, hydrogen and air respectively. Based on the
      above conditions, the satisfactory separation of R- and S-mephenytoin was gained,
      and other interference from urine sample was not found. The linear curves for
      both tested compounds ranged between 12.5 and 2500 microg/L, with a minimum
      detectable concentration of about 6 microg/L. Because of its simplicity,
      rapidity, sensitivity and accuracy, this method has been extensively used for
      testing metabolic ability of S-mephenytoin polymorphic oxidation in the Chinese
      populations and for the determination of the activity of hepatic drug
      metabolizing enzyme CYP2C19 using mephenytoin S/R ratio of the urine samples of
      subjects as an indicator.

PMID- 15739492
TI  - [Studies on difference of fluorescence activity and elution order of propranolol
      enantiomers by reversed-phase high performance liquid chromatography].
AB  - A sensitive RP-HPLC method for the determination of propranolol enantiomers was
      developed. It involves the formation of the monoester of propranolol with
      optically pure (R,R)-O,O'-diacetyl tartaric acid anhydride (DATAAN) in a dry,
      aprotic solvent with an excess of trichloroacetic acid. The resulting
      diastereomeric monoesters were easily resolved on a Shim-pack CLC-ODS column with
      the mobile phase system consisting of different proportions of 2% aqueous acetic
      acid (adjusted with concentrated ammonia to pH 3.48) and 90% aqueous methanol.
      And the column effluent was monitored by a fluorescence detector (lambda(ex) 296
      nm, lambda(em) 340 nm). In our experiment, a very strong difference of the
      fluorescence absorbance of the two diastereomers was observed. After having
      studied chromatographic separation conditions including pH value, ionic strength
      and the volume percent of organic modifier in mobile phase, we presented the
      different configurations of the diastereomers and an intra-molecular hydrogen
      bond which exists only in the (R,R,S) isomer. These could account for the obvious
      difference of fluorescence activity of two diastereomeric monoesters and their
      elution order on the reversed-phase column. Our studies show that the intra
      molecular hydrogen bond plays an important role on the polarity of the
      diastereomeric derivatives which determines their elution order and the
      fluorescence absorbance of the two diastereomers.

PMID- 15739493
TI  - [Analysis of semi-volatile organic compounds in chemical waste by gas
      chromatography/mass spectrometry].
AB  - According to US EPA 8270 method the semi-volatile organic compounds in chemical
      waste were analysed by internal standard method which could eliminate the
      systematic and injection errors and increase the accuracy of the results. Through
      this experiment, ten prior pollutants of US EPA and eleven organic chlorinated
      compounds with concentrations between 0.4 microg/g and 80 microg/g in the waste
      were determined. It is concluded that the waste was hazardous and could not be
      disposed without proper treatment.

PMID- 15739494
TI  - [Determination of human urinary pseudouridine by high performance capillary
      electrophoresis].
AB  - Pseudouridine, mainly as a degradation product of transfer ribonucleic acid, has
      been shown to be excreted in abnormal amounts in the urine of patients with
      cancer and can be used as one of the potentially valuable tumor markers. In this
      paper, a method for the rapid determination of human urinary pseudouridine by
      HPCE is reported. We used a 24 cm x 25 microm i.d. coated capillary and a borate
      buffer solution (0.1 mol/L, pH 8.6), and set the UV detection wavelength at 200
      nm. In this experiment, pseudouridine can be separated completely with uridine
      and anti-tumor drugs (5-fluouridine and methetrexation) and other endogenous
      substances in urine within 4 minutes. Assay precision was determined for
      concentrations of 50 micromol/L and 200 micromol/L as 2.38% and 1.92% for within
      day CV, 3.7% and 2.4% for between-day CV respectively. Sulfosalicylic acid was
      used as internal standard. Linearity, between the concentrations of pseudouridine
      and the corresponding peak height or area ratios of pseudouridine and the
      internal standard, was demonstrated in the 6.25-200 micromol/L range (r>0.9990).
      The detection limit of concentration for pseudouridine was 4 micromol/L. This
      method, with simple sample preparation, good assay precision, lower cost and full
      automation, is an effective means for the assessment of pseudouridine in clinical
      application.

PMID- 15739495
TI  - [Reversed-phase high performance liquid chromatographic analysis of the unfolding
      procedure of bovine insulin].
AB  - A method for measurement of the dynamic unfolding procedure of bovine insulin by
      reversed-phase HPLC has been established. Insulin contains 51 amino acids and two
      intrachain disulfide bridges. The denaturation of bovine insulin was carried in
      dithiothreitol solution at 100 degrees C, and the equilibrium products were
      examined by HPLC at different reaction time. The results show that the
      conformation of insulin has changed before cleavage of the disulfide bonds to A
      and B chains. Bovine insulin, two intermediates and the reduction products A and
      B chains were well separated on a C18 column (4.6 mm x 150 mm) with a linear
      gradient elution of acetonitrile containing 0.1% trifluoroacetic acid. The
      conformation of the unfolding intermediates of insulin was indicated by
      chromatographic method, and the results were verified by matrix-assisted laser
      desorption ionization time of flight mass spectrometry. The method is helpful to
      reveal the conformation changes in the procedures of protein unfolding.

PMID- 15739496
TI  - [Simplex optimization of the automatic gas chromatographic instrument].
AB  - A simplex optimization method developed for the automatic gas chromatography is
      described in this paper. The instrument was developed by ourself based on a gas
      chromatograph and an auto-sampler, which are controlled by a computer through
      several assisting circuit boards. A series of chromatographic function SCRF is
      used in this method for searching the best column temperature for gas
      chromatographic separation of a given sample. A real sample is used for probation
      of this method and the results are discussed.

PMID- 15739497
TI  - [Synthesis of N-salicylidene leucine 3d metal complexes and studies on their thin
      layer chromatography and ultraviolet spectrum].
AB  - The Schiff base derived from salicylaldehyde and leucine and its Mn(II), Co(II),
      Ni(II), Cu(II), Zn(II) complexes were synthesized. The purity of the products
      obtained was confirmed by elemental analysis. The results of elemental analysis
      and molar conductance show that coordination ratio with M(II) is 1:1 and its
      complexes are non-electrolyte in DMF. The thin-layer chromatography behavior of
      complexes was studied on silica gel G plate with ethyl acetate-methanol-acetone
      water-acetic acid (4.44:3.33:2.22:0.25:0.12, V/V) as mobile phase. The results
      show that the Rf value of complexes increases as follows Mn<Zn<Ni<Cu<Co. The
      lambda(max) values of ultraviolet spectra of ligand and complexes are determined
      in methanol and DMSO. The lambda(max) values of complexes increase as follows:
      Mn(II)<Zn(II)<Ni(II)<Cu(II)<Co(II)<ligand. The Rf values and R band lambda(max)
      values of complexes change in the same direction as the stability constants of
      the complexes. This proves that the Rf values of complexes on silica gel G and R
      band lambda(max) values of complexes depend on coordinaton of M(II) with ligand.

PMID- 15739498
TI  - [Study on cross-linked capillary columns coated with polyphenylenesiloxane].
AB  - A new type of cross-linked capillary column coated with polyphenylenesiloxane
      which possesses phenylene in the siloxane main chain has been described in this
      paper. The cross-linking of polyphenylenesiloxane was performed in situ by the
      induction of DCUP. The structure of polyphenylenesiloxane is as followed:
      [structure: see text] The repeatabilities and solvent inextractabilities of the
      column preparations were investigated. For decane and 1-octanol, the values of
      n/L and k' at 120 degrees C were 2800-3100 and 1.0-1.3, 2400-2800 and 5.0-6.0,
      respectively. The k' values of the columns scarcely changed after eluting with
      methylene chloride and pentane. The base-acid property was studied by analyzing
      2,6-dimethylphenol and 2,6-dimethylaniline. Besides, in comparision with OV-17
      and OV-25, the McReynolds' constants of the cross-linked column were also
      determined. The advantages of this kind of column are summarized as (1) easy
      preparation; (2) heat stability improved; and (3) good selectivity for the
      organic compounds which contain halogen, nitro group or phenol.

PMID- 15739499
TI  - [Studies on the pharmacokinetics of chloromycetin in Penaeus chinensis].
AB  - The pharmacokinetic in the aquatic was valued recently. It is advantageous to
      avoid blind with medicine in breed Penaeus chinensis. In this paper, studies on
      the pharmacokinetic parameter of chloromycetin in Penaeus chinensis.
      Chloromycetin is the stronger medicine in controling Penaeus disease. The 2/1000
      contents of antibiotic chloromycetin was added into Penaeus chinensis feed
      producted with conventional method. The length of Penaeus sample was 9.5 cm. The
      test makes the Penaeus chinensis be feeded medicine only one time and get samples
      of Penaeus in different times then cooled immediately. Before analysis dissect,
      weigh, pre-treat properly and then determine contents in muscle, blood,
      intestines-stomach and hepato-pancreas. The method for pharmacokinetic study on
      antibiotic chloromycetin in Penaeus chinensis body was established by HPLC
      determination. The operating conditions were micro-Bondapak-C18 column, 30:70
      (V/V) MeOH/H2O eluent and UV detector. The method is more rapid, accurate and
      sensitive. The correlation coefficient of the calibration curve is 0.9995 in the
      range of 1-50 mg/L.

PMID- 15739500
TI  - [The determination of enantiomeric purity for ibuprofen by high performance
      liquid chromatography].
AB  - Ibuprofen is an excellent anti inflammatory and analgesic drug. It possesses a
      chiral carbon atom in its molecule. For the two enantiomers, only the S(+)-isomer
      is highly active, whereas the R(-)-isomer has very low activity. S-isomer can be
      isolated by resolution from its racemoid and the R-isomer can be racemized under
      basic condition. Consequently it is highly important to determine its
      enantiomeric purity. In this paper, an efficient HPLC method for determination of
      enantiomeric purity for ibuprofen (1) through the formation of a couple of
      diastereomers, N-(S)-(alpha-methylbenzyl)-alpha-methyl-4-(alpha
      methylpropyl)benzeneacetic amide [R,S-(2)], and (S)-(alpha-methylbenzyl)-alpha
      methyl-4-(2-methyl-propyl)benzeneacetic amide [S,S-(2)], was developed using
      Micropak Si-5 column, petroleum ether and ethyl ether (1:1 volume) as eluate and
      UV detector (lambda = 300 nm). The method is convenient, rapid and accurate. The
      accuracy was between 99.71%-100.25%, and the average deviation was 0.064%.

PMID- 15739501
TI  - [Determination of alkaloids in Pericarpium papaveris (Yingsuqiao) by high
      performance capillary electrophoresis].
AB  - Codeine, morphine and papaverine in Pericarpium papaveris (Yingsuqiao) were
      determined by HPCE. These three compounds in Pericarpium papaveris were entirely
      separated. The HPCE conditions were as follows: buffer: 50 mmol/L phosphate, pH
      7.0; V = 25 kV; l(eff.) = 50 cm; L = 64.5 cm; i.d. = 50 microm; lambda = 212 nm;
      T = 25 degrees C; sample size = 15 kPa x s. The recoveries of codeine, morphine
      and papaverine were 96.61%, 95.90% and 95.37% respectively, which shows that this
      method is simple, accurate and reproducible and can be used for the quality
      control of the Chinese herbal medicine.

PMID- 15739502
TI  - [The determination of olaquindox in feeds by HPLC].
AB  - A liquid chromatographic procedure for the determination of olaquindox in feeds
      is described. Chromatography was performed on a PC8-10/S2504 (4.0 mm i.d. x 250
      mm, 10 microm, Shimadzu Co.) column at 30 degrees C by using a mobile phase of
      methanol:water (20:80, V/V ) with a flow rate of 0.8 mL/min and UV detection at
      260 nm. Acetanilide was used as internal standard. Olaquindox was extracted with
      dimethylformamide (DMF) from the feeds. The average recoveries of olaquindox were
      98.58%-101.63% and the relative standard deviations were 2.67%-4.25%. The method
      is simple, rapid, reliable and inexpensive.

PMID- 15739503
TI  - [Separation and detection of seven carbamate pesticides in biological samples by
      solid phase extraction and high performance liquid chromatography].
AB  - Methomyl, metolcarb, propoxur, carbaryl, isoprocarb, diuron and bassa are all
      carbamate pesticides. In this paper, a reversed-phase HPLC method is described
      for analysis of these carbamate pesticides in biological samples with Spherisorb
      C18 column (150 mm x 2.0 mm i.d., 5 microm), 60:40 (V/V) MeOH-H20 eluent and
      photodiode array detector. These pesticides were identified by their spectrum
      characteristics and retention times. Their quantity was determined by their peak
      area. The biological samples were extracted with C18 cartridge and eluted with
      ethyl acetate, and then analysed by HPLC. The sensitivity of detection for the
      seven carbamates was in the range of 1-2 mg/L of blood sample and 5-10 mg/L of
      urine sample. The recoveries of blood and urine samples were 70%-80% and 65%-82%,
      respectively. The method is simple, rapid and highly sensitive.

PMID- 15739504
TI  - [Plasma glutamine level monitored with high performance liquid chromatography for
      patient infusing glutamine after small bowel transplantation].
AB  - To promote the restoration of the structure and functions of the graft intestine
      for a patient with small bowel transplantation, the authors gave intravenous
      infusion of 5% glutamine to the patient and the blood glutamine levels were
      determined with HPLC technique. The ultrafiltration technique was adapted to
      remove blood proteins. Good separation could be achieved when using micro
      Bondapak C18 as separation cartridge, phthaldialdehyde as derivatization agent,
      gradient elution with methanol and phosphate buffer and detection at wavelength
      of 340 nm. The recovery rate was 90% to 105% and the lower limit of detection was
      40 micromol/L with satisfactory separation. The results of this method are proved
      to be a timely and reliable indicator for glutamine level in blood for patients
      of small bowel transplantation with glutamine infusion.

PMID- 15739505
TI  - [A high performance liquid chromatographic method for the determination of
      teniposide in brain tissue using electro-chemical detection].
AB  - A reversed-phase HPLC method for the determination of teniposide in brain tissue
      is described. Teniposide can be separated on a Hypersil ODS column with a mobile
      phase of methyl alcohol-water-acetic acid (56:41:3, V/V) and flow rate of 0.8
      mL/min (10 MPa). Column temperature was 35 degrees C and operating potentials for
      electrochemical detection was 0.70 V. To 50 mg brain tissue were 1 mL 50%
      ammonium sulfate and 4 mL ethyl acetate. The sample was vortexed for 5 min and
      ultrasonically agitated for 15 min, then centrifuged at 3000 r/min for 15 min.
      The upper (organic) layer was collected and the lower layer reextracted with 4 mL
      of ethyl acetate by vigorously vortexing, then centrifuged at 3000 r/min for 15
      min. The organic layer was combined with the previously collected ethyl acetate
      layer. This organic extract was dried under a gentle nitrogen stream, and the
      residue was reconstituted with 1 mL internal standard of guaifenesinum before
      HPLC analysis. The linear range was 0.1-10.0 mg/L, and the detection limit 0.1
      mg/L. Intra-day and inter-day RSD for assaying brain tissue sample were 0.87% and
      1.41%, respectively. The average recovery was 92.87% with coefficient of
      variation of 2.35%.

PMID- 15739506
TI  - [HPLC determination of diltiazem in human serum and its pharmacokinetic
      parameters].
AB  - A simple and sensitive reversed-phase liquid chromatographic method has been
      developed and validated for the analysis of diltiazem in human serum and the
      study of pharmacokinetics of the drug in human body. Diltiazem and diazepam
      (internal standard) in serum were extracted with hexane-chloroform-isopropanol
      (60:40:5, V/V), and then measured by HPLC using a Spherisorb C18 column as
      stationary phase and a methanol-water triethylamine as mobile phase. Diltiazem
      was quantified by ultraviolet absorbance at 239 nm. The method proved to be
      linear in the clinical range of 15-300 microg/L with a regression coefficient of
      0.9997. The lower limit of detection of diltiazem in serum was 3 microg/L. Intra
      day and inter-day coefficients of variation of assay for diltiazem in serum were
      3.5%-6.8% (n=7) and 6.2%-8.4% (n=5), respectively. The recoveries of diltiazem
      were 91%-104% for serum. The method has been used to determine diltiazem in serum
      samples from eight volunteers and provided data on the pharmacokinetics of the
      drug. The results inferred that diltiazem is absorbed rapidly and had a
      relatively short half-life time in healthy individuals. The data obtained was
      fitted with PKBP-N1 program on computer to study the pharmacokinetics. The
      results showed that the peak level in serum averaged 118.5 microg/L +/- 14.3
      microg/L at 3.1 h +/- 0.4 h, and the areas under the drug concentration curves
      (AUC) was 793.1 microg x h/L +/- 83.1 microg x h/L.

PMID- 15739508
TI  - [Gas chromatographic analysis of methyl methacrylate and methanol in its
      esterification mixture].
AB  - A fast, simple and accurate gas chromatographic method is established for
      determining the content of methyl methacrylate (MMA) and methanol in the
      esterification mixture of methacrylic acid with methanol in the presence of
      sulfuric acid. In the measurement, polyethylene glycol-20M/sodium hydroxide was
      adopted as liquid phase, coated on the acid-washed 201 pink support. n-Heptane
      was used as the internal standard and the correction factors of MMA and methanol
      obtained were 1.65 and 4.10, respectively. It is significant for this method to
      be used to control MMA production by acetone cyanohydrin method and to improve
      the production technology.

PMID- 15739507
TI  - [Determination of berberine in human serum by reversed-phase high performance
      liquid chromatography].
AB  - Berberine is a safe and effective anti-arrhythmic drug. We do not clearly know
      about the dose-effect relationship. Besides, berberine is not fit for
      administration by i.m. and i.v.. Therefore, it is necessary to build a PD model
      of berberine, study its pharmacodynamics parameters in vivo, and provide a
      concrete criteria in the clinical usage. In this article, we set up a method for
      determination of concentration of berberine in human serum by RP-HPLC with
      Lichrosorb RP-18 column (250 mm x 4 mm) and mobile phase of MeOH containing 0.15%
      triethylamine. The content of berberine was determined by the external standard
      method with UV detector at 347 nm. The linear range was 0.2-2 mg/L (r = 0.9996).
      The detectable limit was 2.55 ng. The average recovery was 90.73% and the
      coefficients of variation were below 8.0%. The method is sensitive and accurate.

PMID- 15739509
TI  - [Analysis of hexamethylene bisacetamide in biological fluids and tissues by RP
      HPLC].
AB  - This paper describes the analysis of anticancer drug hexamethylene bisacetamide
      (HMBA) in biological fluids and tissues by RP-HPLC. The samples of plasmas, urine
      and tissues from cancer mice and rabbits were first used with methanol for
      pretreatment to remove protein impurity, then analyzed by RP-HPLC on an ODS
      column. The mobile phase was methanol/water (70/30, V/V), UV detection is
      employed at 210 nm. 153 samples were analyzed and good results were obtained. The
      recoveries of 93.3%-104% with a relative standard deviation of 0.04%. The
      regression equation is: Y = 0.32X - 1.07, with a linear correlation coefficient
      of 0.998 and the linear range of HMBA is 0 to 1000 mg/L. A sample analysis can be
      completed within 13 minutes. This method could be satisfactorily applied not only
      for the analysis of HMBA but probably also for the analysis of other drugs in
      biological fluids and tissues.

PMID- 15739510
TI  - The utility industry response to Title IV: generation mix, fuel choice, emissions
      and costs.
AB  - The Clean Air Act Amendments of 1990 incorporate, for the first time, provisions
      aimed specifically at the control of acid rain. These provisions restrict
      emissions of sulfur dioxide and oxides of nitrogen from electric power generating
      stations. The restrictions on sulfur dioxide take the form of an overall cap on
      the aggregate emissions from major generating plants, allowing substantial
      flexibility in the industry's response to those restrictions. This report
      describes one response scenario through the year 2030, which was examined by
      simulation of the utility industry under assumptions consistent with a reference
      case that was used for analysis of the National Energy Strategy. Emissions that
      would result from the use of existing and new capacity and the associated
      additional costs of meeting demand subject to the emission limitations imposed by
      the Clean Air Act are projected. Fuel use effects, including coal market shifts,
      consistent with the response scenario are also described. These results, while
      dependent on specific assumptions for this scenario, provide insight into the
      general character of the likely utility industry response to Title IV.

PMID- 15739511
TI  - Overview and implications of U.S. sanitary landfill practice.
AB  - This paper is a summary of observations and trends regarding landfill practice
      based on a fifteen state, four-and-a-half month tour of facilities and
      professionals involved in municipal solid waste management, supplemented by 25
      years of experience in the field. Modern landfills tend to be well designed and
      operated, with an emphasis on containment of waste and products of decomposition
      through liner systems and cover design, plus good operating practice. Forces
      leading to our concept of modern landfills are based on a history of inadequate
      landfills and their impacts, and on long-term liability issues, but also stem
      from a lack of responsibility by the public and their representatives for
      handling their own waste. While modern landfills incorporate many improvements
      over previous facilities, the driving forces shaping landfill design now and in
      the future are unfortunately not based on sound technical and managerial
      principals and could lead to future problems. The trend to drier landfills,
      thereby prolonging decomposition, is of special concern in this regard.

PMID- 15739512
TI  - Summary of the 1992 EPA/A&WMA International Symposium: measurement of toxic and
      related air pollutants.
AB  - A joint conference cosponsored for the seventh year by the Atmospheric Research
      and Exposure Assessment Laboratory (AREAL) of the U.S. Environmental Protection
      Agency (EPA) and the Air & Waste Management Association (A&WMA) was held in
      Durham, North Carolina, May 4-8, 1992. The technical program consisted of 200
      presentations held in 23 technical sessions and covered recent advances in
      ambient and source measurement techniques for air pollutants. The symposium was
      attended by almost a thousand professionals from the United States and other
      countries, covered a wide range of measurement topics, and was supported by 90
      exhibitors of instrumentation and consulting services. This overview highlights
      the technical presentations of the symposium.

PMID- 15739513
TI  - Superfund soil cleanup: developing the Piazza Road remedial design.
AB  - A statistical approach was used to develop the remediation and soil sampling
      strategy at the Piazza Road dioxin site (an EPA Superfund site in Missouri). The
      source of the dioxin was contaminated waste oil that was used as a dust
      suppressant. This site was used as a test case to determine if a "surgical"
      remedial design could be developed. This new approach was compared to the
      historical approach taken by U.S. EPA Region 7 in Missouri. A pilot study
      provided information on the local spatial pattern of dioxin, so that sampling
      designs could be evaluated and costs of remediation could be estimated for
      different remedial strategies. Sampling designs were evaluated by a Monte Carlo
      approach, where the laboratory analytical error and sampling error due to spatial
      variation of dioxin were modeled based on the results of the pilot study and the
      historical site data. The optimal cleanup unit size was determined to be 14x14
      ft, or 1/24th of the historical cleanup unit size. A companion paper describes
      the performance achieved and the dollar 5,900,000 cost savings that resulted from
      applying the improved design. This case study clearly shows the value of
      environmental data, where the use and quality of the data are established as a
      part of planning the site remediation.

PMID- 15739514
TI  - Full-scale evaluation of the thermal stability-based hazardous organic waste
      incinerability ranking.
AB  - The results of a full-scale evaluation of the thermal stability-based hazardous
      organic waste incinerability ranking are presented. Tests were conducted for a
      surrogate mixture consisting of sulfur hexafluoride, chlorobenzene, toluene,
      tetrachloroethene, methylene chloride, 2-chloropropene and 1,1,1-trichloroethane
      under nominal incinerator operating conditions. Based on median surrogate DREs,
      the results indicated that the pyrolytic ranking was statistically significant at
      the 90 percent confidence level while the oxidative ranking was statistically
      significant at the 97.5 percent confidence level. The heat of combustion ranking
      failed to give a statistically significant correlation at the 90 percent
      confidence level. The statistical success of the thermal stability rankings and
      statistical failure of the heat of combustion ranking suggest that chemical
      reaction kinetics controlled the relative emission rates of the surrogate
      compounds during these tests.

PMID- 15739515
TI  - Distribution of sulfur dioxide in the atmosphere of Jiddah, Saudi Arabia.
AB  - The aridity of Saudi Arabia, in general, makes air pollution studies very
      important, not just on a local level but also on an international level. A
      comprehensive field study of atmospheric sulfur dioxide (SO2) concentration was
      conducted in Jiddah, Saudi Arabia (one of the fastest growing cities in the
      world) for the period 1984 through 1987. Sulfur dioxide trends have been
      developed for five stations in Jiddah. Daily, monthly and annual means, maximum
      and mean maximum are reported. The average SO2 concentration for 1984, 1985, 1986
      and 1987 was 0.035 microL/L, 0.039 microL/L, 0.035 microL/L and 0.033 microL/L,
      respectively. The four-year average SO2 concentration was 0.036 microL/L and a
      maximum of 0.832 microL/L was recorded once at station 104 in 1985. A slight
      decrease in SO2 concentration from 1984 to 1987 was observed. The statistical
      significance of data and background information for air quality standards for the
      city are discussed. Analysis of data shows a lower mean than any international
      air quality standard.

PMID- 15739516
TI  - Comparison of chemiluminescence and ultraviolet ozone monitor responses in the
      presence of humidity and photochemical pollutants.
AB  - The effect of water vapor and other pollutants on ozone monitoring instruments
      was investigated. Five UV-type and two chemiluminescence-type monitors were
      employed in this study. The results of the study indicate that in systems
      containing ozone, water vapor and zero air only, the UV-based monitors showed
      negligible effects due to humidity. On average, the UV monitors were within 0.5
      percent of independently determined ozone values judged to be extremely accurate.
      The chemiluminescence-based monitors showed systematically higher readings than
      the UV monitors with added water vapor. The effect was found to be linear with
      water vapor concentration with an average positive deviation of 3.0 percent per
      percent H2O at 25 degrees C. For these measurement, ozone concentrations ranged
      from 85 to 320 ppbv and water concentrations from 1 to 3 percent (i.e., dew point
      temperatures from 9 to 24 degrees C). These results are largely in agreement with
      previous studies conducted to measure this interference, although the present
      study extends the range of water concentrations tested. Studies were also
      performed with a smog chamber with simulated polluted air (containing paraffinic,
      olefinic and aromatic hydrocarbon precursors) and varying relative humidities.
      Although the presence of water vapor did not appear to represent a substantial
      interference in these systems, a positive interference was observed with the UV
      monitors. This interference was likely a result of the presence of toluene and
      some of its aromatic photooxidation products (e.g., benzaldehyde), which can be
      partially removed from the reference stream by the ozone scrubber within the UV
      monitor. If the compound absorbs radiation at 254 nm, it is detected as ozone.
      However, when the results are scaled back to ambient concentrations of toluene
      and NO(x), the effect appears to be very minor (ca. 3 percent under the study
      conditions). It is concluded that under atmospheric conditions at moderate
      pollution and relative humidity levels, both types of instruments can give
      accurate measurements of the ozone concentration. These potential effects should
      be recognized when conducting ambient ozone measurements.

PMID- 15739517
TI  - Pollutant emission rates from a radiant fiber-matrix gas burner.

PMID- 15739518
TI  - Update on ozone trends in California's South Coast Air Basin.

PMID- 15739519
TI  - Corona destruction: an innovative control technology for VOCs and air toxics.
AB  - This paper discusses the work and results to date leading to the demonstration of
      the corona destruction process at pilot scale. The research effort in corona
      destruction of volatile organic compounds (VOCs) and air toxics has shown
      significant promise for providing a valuable contribution to critical U.S.
      Environmental Protection Agency and national goals of reducing the health effects
      associated with exposures to hazardous air pollutants. The corona destruction
      technology could be especially useful in future years in helping industry meet
      the residual risk requirements of the Clean Air Act Amendments of 1990. Since
      1988, EPA has conducted research in the area of corona destruction of VOCs and
      air toxics. EPA's interest in corona destruction of molecular species started
      with modeling of a point-plane reactor for destroying toxic organic compounds.
      EPA's goal is to develop a technology capable of controlling low concentration
      streams at low capital and operating costs. The purpose of this work is to
      develop an industrial scale corona reactor capable of efficiently and cost
      effectively destroying VOCs and air toxics at ambient temperature and pressure.
      Results show that corona destruction is a promising control technology for many
      VOC-contaminated air streams, especially at low concentrations. Cost comparisons
      are presented for corona destruction and conventional control devices, carbon
      adsorption, catalytic incineration and thermal incineration.

PMID- 15739520
TI  - Sciatica of nondisc origin and piriformis syndrome: diagnosis by magnetic
      resonance neurography and interventional magnetic resonance imaging with outcome
      study of resulting treatment.
AB  - OBJECT: Because lumbar magnetic resonance (MR) imaging fails to identify a
      treatable cause of chronic sciatica in nearly 1 million patients annually, the
      authors conducted MR neurography and interventional MR imaging in 239 consecutive
      patients with sciatica in whom standard diagnosis and treatment failed to effect
      improvement. METHODS: After performing MR neurography and interventional MR
      imaging, the final rediagnoses included the following: piriformis syndrome
      (67.8%), distal foraminal nerve root entrapment (6%), ischial tunnel syndrome
      (4.7%), discogenic pain with referred leg pain (3.4%), pudendal nerve entrapment
      with referred pain (3%), distal sciatic entrapment (2.1%), sciatic tumor (1.7%),
      lumbosacral plexus entrapment (1.3%), unappreciated lateral disc herniation
      (1.3%), nerve root injury due to spinal surgery (1.3%), inadequate spinal nerve
      root decompression (0.8%), lumbar stenosis (0.8%), sacroiliac joint inflammation
      (0.8%), lumbosacral plexus tumor (0.4%), sacral fracture (0.4%), and no diagnosis
      (4.2%). Open MR-guided Marcaine injection into the piriformis muscle produced the
      following results: no response (15.7%), relief of greater than 8 months (14.9%),
      relief lasting 2 to 4 months with continuing relief after second injection
      (7.5%), relief for 2 to 4 months with subsequent recurrence (36.6%), and relief
      for 1 to 14 days with full recurrence (25.4%). Piriformis surgery (62 operations;
      3-cm incision, transgluteal approach, 55% outpatient; 40% with local or epidural
      anesthesia) resulted in excellent outcome in 58.5%, good outcome in 22.6%,
      limited benefit in 13.2%, no benefit in 3.8%, and worsened symptoms in 1.9%.
      CONCLUSIONS: This Class A quality evaluation of MR neurography's diagnostic
      efficacy revealed that piriformis muscle asymmetry and sciatic nerve
      hyperintensity at the sciatic notch exhibited a 93% specificity and 64%
      sensitivity in distinguishing patients with piriformis syndrome from those
      without who had similar symptoms (p < 0.01). Evaluation of the nerve beyond the
      proximal foramen provided eight additional diagnostic categories affecting 96% of
      these patients. More than 80% of the population good or excellent functional
      outcome was achieved.

PMID- 15739521
TI  - Use of the Solis cage and local autologous bone graft for anterior cervical
      discectomy and fusion: early technical experience.
AB  - OBJECT: The authors prospectively evaluated the clinical and radiological
      outcomes after anterior cervical discectomy and fusion (ACDF) involving placement
      of a Solis cage and local autograft in patients who presented with symptomatic
      cervical spondylosis. METHODS: Twenty-two consecutive patients underwent ACDF for
      radiculopathy (13 cases), myeloradiculopathy (eight cases), or myelopathy alone
      (one case) and were assessed at 3, 6, and 12 months. Plain cervical spine
      radiography demonstrated a significant change in both local (p < 0.05) and
      regional (p < 0.05) kyphotic angles as well as an increase in segmental height (p
      < 0.05). At 12 months, plain radiography demonstrated Grades I, II, and III new
      bone formation in two, three, and 17 patients, respectively. Clinical outcomes
      were assessed using a visual analog scale for both neck and arm pain and a
      modified Japanese Orthopaedic Association (JOA) scale for myelopathy. There was a
      significant improvement in both arm (p < 0.05) and neck pain (p < 0.05). At 12
      months, 16 (84%) of 19 and 19 (86%) of 22 patients reported complete resolution
      of arm pain and neck pain, respectively. There was a significant improvement in
      JOA scores following surgery (p < 0.05). There were two complications in the
      series: one case of deep venous thrombosis and one case of postoperative arm pain
      that resolved after conservative treatment. There were no technical
      complications. CONCLUSIONS: Early experience with Solis cage-augmented ACDF
      indicates good clinical and radiological outcomes; additionally, there are the
      advantages of absent donor site morbidity and anterior plate system-related
      morbidity.

PMID- 15739522
TI  - Recurrent laryngeal nerve palsy during anterior cervical spine surgery: a
      prospective study.
AB  - OBJECT: Recurrent laryngeal nerve (RLN) palsy is a well-known complication of
      cervical spine surgery. Nearly all previous studies were performed without
      laryngoscopy in asymptomatic patients. This prospective study was undertaken to
      discern the true incidence of RLN palsy. Because not every RLN palsy is
      associated with hoarseness, the authors conducted a prospective study involving
      the use of pre- and postoperative laryngoscopy. METHODS: Prior to anterior
      cervical spine surgery preoperative indirect laryngoscopy was performed in 123
      patients to evaluate the status of the vocal cords as a sign of function of the
      RLN. To assess postoperative status in 120 patients laryngoscopy was repeated,
      and in cases of vocal cord malfunction follow-up examination was conducted 3
      months later. In the group of 120 patients who attended follow-up examination,
      two (1.6%) had experienced a preoperative RLN palsy without hoarseness.
      Postoperatively the rate of clinically symptomatic RLN palsy was 8.3%, and the
      incidence of RLN palsy not associated with hoarseness (that is, clinically
      unapparent without laryngoscopy) was 15.9% (overall incidence 24.2%). At 3-month
      follow-up evaluation the rate had decreased to 2.5% in cases with hoarseness and
      10.8% without hoarseness. Thus, the overall rate of early persisting RLN palsy
      was 11.3%. CONCLUSIONS: Laryngoscopy revealed that the true incidence of initial
      and persisting RLN palsy after anterior cervical spine surgery was much higher
      than anticipated. Especially in cases without hoarseness this could be proven,
      but the initial incidence of hoarseness was higher than expected. Only one third
      of new RLN palsy cases could be detected without laryngoscopy. Resolution of
      hoarseness was approximately 70% in those with preoperative hoarseness. The true
      rate of RLN palsy underscores the necessity to reevaluate the surgery- and
      intubation-related techniques for anterior cervical spine surgery and to reassess
      the degree of presurgical patient counseling.

PMID- 15739523
TI  - Surgical technique and results of endoscopic anterior spinal canal decompression.
AB  - OBJECT: Decompression of the spinal canal in the management of thoracolumbar
      trauma is controversial, but many authors have advocated decompression in
      patients with severe canal compromise and neurological deficits. Anterior
      decompression, corpectomy, and fusion have been shown to be more reliable for
      spinal canal reconstruction than posterior procedures; however, traditional
      anterior-access procedures, thoracotomy, and thoracoabdominal approaches are
      associated with significant complications. Endoscopy-guided spinal access avoids
      causing these morbidities, but it has not been shown to yield equivalent results
      in spinal canal clearance. This study was conducted to demonstrate the
      effectiveness of endoscopic spinal canal decompression and reconstruction
      quantitatively by using pre- and postoperative computerized tomography (CT)
      scanning. METHODS: Thirty patients with thoracolumbar canal compromise underwent
      endoscopic anterior spinal canal decompression, interbody reconstruction, and
      stabilization for fractures (27 cases), and tumor, infection, and severe
      degenerative disc disease (one case each). The mean follow-up period was 42
      months (range 24 months-6 years). Neurological examinations, Frankel grades,
      radiological studies, and intraoperative findings were prospectively collected.
      Spinal canal clearance quantified on pre- and postoperative CT scans improved
      from 55 to 110%. A total of 25% of patients with complete paraplegia and 65% of
      those with incomplete neurological deficit improved neurologically. The
      complication rate was 16.7% and included one reintubation, two pleural effusions,
      one intercostal neuralgia, and one persistent lesion of the sympathetic chain.
      CONCLUSIONS: The authors describe the endoscopic technique of anterior spinal
      canal decompression in the thoracolumbar spine. The morbidities associated with
      an open procedure were avoided, and excellent spinal canal clearance was
      accomplished as was associated neurological improvement.

PMID- 15739524
TI  - Axial load-dependent cervical spinal alterations during simulated upright
      posture: a comparison of healthy controls and patients with cervical degenerative
      disease.
AB  - OBJECT: The objectives of this study were to simulate the upright loading
      condition in the cervical spine by applying a new compression device during
      supine posture and to assess intervertebral angles and cross-sectional areas of
      the spinal cord and dural tube before and during axial compression. METHODS: A
      magnetic resonance (MR) imaging-compatible device was developed to create axial
      compression with the patient in the supine position. Lateral radiographs were
      obtained in upright and supine positions with an axial load of 0% (supine) and by
      applying a cervical compression device at 7, 10, and 13% of body weight (BW) in
      18 control individuals and seven symptomatic patients with cervical degenerative
      disc disease (DDD). Additionally, cervical MR images acquired in 17 controls and
      12 patients were compared before and during an axial load of 8.4% BW in terms of
      anteroposterior diameter and cross-sectional area of the dural sac. The supine
      intervertebral angles with loads of 0, 7, 10, and 13% of the individuals' BW
      relative to upright posture were -8.1+/-1.3, -2.3+/-1.4, 1.3+/-1.9, and 2.8+/-2
      degrees, respectively. Subsequent axial force was interpolated as 8.9% of BW to
      simulate upright cervical spine alignment. Under an axial loading similar to that
      created by the upright posture, the dural sac narrowed at the C5-6 interspace in
      asymptomatic individuals and at the C6-7 interspace in patients with cervical
      DDD. CONCLUSIONS: This cervical compression device may be a useful tool to
      simulate upright cervical spinal alignment. The results of this study help in
      understanding the pathophysiology of symptoms related to cervical degenerative
      disorders in upright posture.

PMID- 15739525
TI  - Modern imaging of spinal tuberculosis.
AB  - Spinal tuberculosis (Pott disease) is uncommon in developed countries. On imaging
      studies diagnosis of this lesion may not be considered or it might be mistaken
      for pyogenic osteomyelitis. Features most strongly indicative of a diagnosis of
      spinal tuberculosis are relative sparing of the disc space, large paraspinous
      abscesses, a thick rim of enhancement around the paraspinous and intraosseous
      abscesses, calcifications within the paraspinous collections, and a fragmentary
      pattern of osseous destruction. As the disease progresses, there is worsening of
      the osseous destruction, leading to collapse of the vertebral body and eventual
      progression to kyphotic deformity. Based on recent experience, the authors review
      the major imaging characteristics associated with spinal tuberculosis and
      describe the typical course of the disease as documented on plain radiographs,
      computerized tomography scans, and magnetic resonance images.

PMID- 15739526
TI  - Chronological changes of postsympathectomy compensatory hyperhidrosis and
      recurrent sweating in patients with palmar hyperhidrosis.
AB  - OBJECT: The author sought to investigate the temporal changes of
      postsympathectomy compensatory hyperhidrosis and recurrent sweating in patients
      with primary palmar hyperhidrosis. METHODS: The author examined 91 consecutive
      patients for this prospective 6-year study. The patients were interviewed at
      least twice during a 6-month interval; the first follow up was conducted at a
      median of 1.7 years after surgery (range 2.5-60.5 months). Overall, 24 patients
      (26.4%) were followed for more than 2 years. Attention was focused on patient
      satisfaction and the incidence of compensatory hyperhidrosis and recurrent
      sweating. The overall mean patient satisfaction rate was 78%, with a median 80%
      improvement on a visual analog scale from 0% (poor) to 100% (excellent). Overall,
      88 patients (96.7%) developed compensatory hyperhidrosis, with the mean initial
      occurrence at 8.2 weeks. The symptoms of compensatory hyperhidrosis progressively
      worsened to the maximum degree within another 2 weeks after onset (mean 10.3+/
      1.83 weeks). In 19 patients (21.6%), symptoms of compensatory hyperhidrosis
      improved spontaneously within 3 months after sympathectomy (mean 13.3 weeks).
      Postoperative compensatory hyperhidrosis occurred in 71.4% of patients within the
      1st year. Recurrent sweating occurred in only 17.6% of patients. None of these
      patients required repeated operation. The earliest onset of recurrent sweating
      was noted at 2 weeks postoperatively by three patients, and the mean initial
      postoperative reccurrence was 32.7 weeks after surgery. CONCLUSIONS: Compensatory
      hyperhidrosis and recurrent sweating are normal thermoregulatory responses that
      occurred after upper thoracic sympathectomy. Compensatory hyperhidrosis was more
      prevalent and developed earlier than recurrent sweating. The severity of both
      compensatory hyperhidrosis and recurrent sweating symptoms remained stable 6
      months after surgery.

PMID- 15739527
TI  - Atlantoaxial transarticular screw fixation: a review of surgical indications,
      fusion rate, complications, and lessons learned in 191 adult patients.
AB  - OBJECT: In this, the first of two articles regarding C1-2 transarticular screw
      fixation, the authors assessed the rate of fusion, surgery-related complications,
      and lessons learned after C1-2 transarticular screw fixation in an adult patient
      series. METHODS: The authors retrospectively reviewed 191 consecutive patients
      (107 women and 84 men; mean age 49.7 years, range 17-90 years) in whom at least
      one C1-2 transarticular screw was placed. Overall 353 transarticular screws were
      placed for trauma (85 patients), rheumatoid arthritis (63 patients), congenital
      anomaly (26 patients), os odontoideum (four patients), neoplasm (eight patients),
      and chronic cervical instability (five patients). Among these, 67 transarticular
      screws were placed in 36 patients as part of an occipitocervical construct.
      Seventeen patients had undergone 24 posterior C1-2 fusion attempts prior to
      referral. The mean follow-up period was 15.2 months (range 0.1-106.3 months).
      Fusion was achieved in 98% of cases followed to commencement of fusion or for at
      least 24 months. The mean duration until fusion was 9.5 months (range 3-48
      months). Complications occurred in 32 patients. Most were minor; however, five
      patients suffered vertebral artery (VA) injury. One bilateral VA injury resulted
      in patient death. The others did not result in any permanent neurological
      sequelae. CONCLUSIONS: Based on this series, the authors have learned important
      lessons that can improve outcomes and safety. These include techniques to improve
      screw-related patient positioning, development of optimal instrumentation,
      improved screw materials and design, and defining the role for stereotactic
      navigation. Atlantoaxial transarticular screw fixation is highly effective in
      achieving fusion, and the complication rate is low when performed by properly
      trained surgeons.

PMID- 15739528
TI  - Atlantoaxial transarticular screw fixation: a review of surgical indications,
      fusion rate, complications, and lessons learned in 67 pediatric patients.
AB  - OBJECT: In this, the second of two articles regarding C1-2 transarticular screw
      fixation, the authors discuss their surgical experience in treating patients 16
      years of age and younger, detailing the rate of fusion, complication avoidance,
      and lessons learned in the pediatric population. METHODS: The authors
      retrospectively reviewed 67 consecutive patients (23 girls and 44 boys) younger
      than 16 years of age in whom at least one C1-2 transarticular screw fixation
      procedure was performed. A total of 127 transarticular screws were placed in
      these 67 patients whose mean age at time of surgery was 9 years (range 1.7-16
      years). The indications for surgery were trauma in 24 patients, os odontoideum in
      22 patients, and congenital anomaly in 17 patients. Forty-four patients underwent
      atlantoaxial fusion and 23 patients underwent occipitocervical fusion. Two of the
      67 patients underwent halo therapy postoperatively. All patients were followed
      for a minimum of 3 months. In all 67 patients successful fusion was achieved.
      Complications occurred in seven patients (10.4%), including two vertebral artery
      injuries. CONCLUSIONS: The use of C1-2 transarticular screw fixation, combined
      with appropriate atlantoaxial and craniovertebral bone/graft constructs, resulted
      in a 100% fusion rate in a large consecutive series of pediatric patients. The
      risks of C1-2 transarticular screw fixation can be minimized in this population
      by undertaking careful patient selection and meticulous preoperative planning.

PMID- 15739529
TI  - Endoscopic partial laminectomy for cervical myelopathy.
AB  - OBJECT: The authors report the results of endoscopic partial laminectomy
      performed in 10 patients with degenerative cervical compressive myelopathy.
      METHODS: Endoscopic partial laminectomy was performed safely in 10 patients with
      cervical myelopathy. All of the patients experienced symptomatic improvement with
      slight postoperative wound pain. The mean operative duration was 164+/-35 minutes
      and the mean intraoperative blood loss was 45.5+/-27 ml. CONCLUSIONS: Endoscopic
      partial laminectomy may be used as a minimally invasive alternative for the
      treatment of cervical compressive myelopathy.

PMID- 15739530
TI  - Biomechanical comparison of C1-2 posterior fixation techniques.
AB  - OBJECT: In a nondestructive, repeated-measures in vitro flexibility experiment,
      the authors compared the acute stability of C1-2 after placement of C-1 lateral
      mass and C-2 pars interarticularis (LC1-PC2) instrumentation with that of C1-2
      transarticular screw fixation. METHODS: The effect of C-1 laminectomy and C1-2
      interspinous cable/graft fixation on LC1-PC2 stability was studied. Screw pullout
      strengths were also compared. Seven human cadaveric occiput-C3 specimens were
      loaded nondestructively with pure moments while measuring nonconstrained
      atlantoaxial motion. Specimens were tested with graft alone, LC1-PC2 alone, LC1
      PC2 combined with C-1 laminectomy, and graft-augmented LC1-PC2. Interspinous
      cable/graft fixation significantly enhanced LC1-PC2 stability during extension.
      After C-1 laminectomy, the LC1-PC2 construct allowed increased motion during
      flexion and extension. There was no significant difference in lax zone or range
      of motion between LC1-PC2 fixation and transarticular screw fixation, but graft
      assisted transarticular screws yielded a significantly smaller stiff zone during
      extension. The difference in pullout resistance between C-1 lateral mass screws
      and C-2 pars interarticularis screws was insignificant. The LC1-PC2 region
      restricted motion to within the normal range during all loading modes. Atlantal
      laminectomy reduced LC1-PC2 stability during flexion and extension. CONCLUSIONS:
      The instrumentation-augmented LC1-PC2 construct performed biomechanically
      similarly to the C1-2 transarticular screw fixation. The LC1-PC2 construct
      resisted flexion, lateral bending, and axial rotation well. The weakness of the
      LC1-PC2 fixation in resisting extension can be overcome by adding an interspinous
      graft to the construct.

PMID- 15739531
TI  - Biomechanical evaluation of a bioresorbable odontoid screw.
AB  - OBJECT: The authors tested the ability of a resorbable cannulated lag screw
      composed of a polylactide copolymer to repair Type II odontoid fractures. The
      resorbable screw was evaluated for its ability to restore strength and stiffness
      to the fractured odontoid process compared with traditional titanium screws.
      METHODS: Type II odontoid fractures were created in 14 human cadaveric C-2
      vertebrae by applying a posterolaterally directed load and piston displacement
      was measured. Seven of these specimens were repaired using metal screws and seven
      were repaired using resorbable screws. Specimens were reinjured using the same
      mechanism as the initial fracture. Values of ultimate strength and stiffness
      during failure were statistically compared between metal and resorbable screws
      and between initial fracture and reinjury. CONCLUSIONS: The stiffness and
      ultimate strength during initial fracture were significantly greater than those
      during reinjury in specimens repaired using resorbable screws or titanium screws
      (p < 0.001). The resorbable and titanium screws both restored 31% of the initial
      ultimate strength of the intact specimen (p = 0.95). The stiffness of the
      fractured odontoid process was restored to 15 and 23% of its initial value by
      repair with resorbable and metal screws, respectively (p = 0.07). The mode of
      failure in resorbable screws was usually breakage or bending, whereas that in
      metal screws was consistently cutout of the proximal shaft of the screw through
      the anterior C-2 vertebral body.

PMID- 15739532
TI  - Multidirectional flexibility analysis of cervical artificial disc reconstruction:
      in vitro human cadaveric spine model.
AB  - OBJECT: This in vitro experimental study was conducted to investigate the initial
      biomechanical effect of artificial intervertebral disc replacement in the
      cervical spine. The multidirectional flexibility of replaced and adjacent spinal
      segments were analyzed using a cadaveric cervical spine model. METHODS: The
      following three cervical reconstructions were sequentially performed at the C5-6
      level after anterior discectomy in seven human cadaveric occipitocervical spines:
      anterior artificial disc replacement with a bioactive three-dimensional (3D)
      fabric disc (FD); anterior iliac bone graft; and anterior plate fixation with
      iliac bone graft. Six unconstrained pure moments were applied with a 6-df spine
      simulator, and 3D segmental motions at the operative and adjacent segments were
      measured with an optoelectronic motion measurement system. The 3D FD group
      demonstrated statistically equivalent ranges of motion (ROMs) when compared with
      intact values in axial rotation and lateral bending. The 45% increase in flexion
      extension ROM was demonstrated in 3D FD group; however, neutral zone analysis did
      not reach statistical significance between the intact spine and 3D FD. The
      anterior iliac bone graft and iliac bone graft reconstructions demonstrated
      statistically lower ROMs when compared with 3D FD in all loading modes (p <
      0.05). The adjacent-level ROMs of the 3D FD group demonstrated nearly
      physiological characteristics at upper and lower adjacent levels. Excellent
      stability at the interface was maintained during the whole testing without any
      device displacement and dislodgment. CONCLUSIONS: The stand-alone cervical 3D FD
      demonstrated nearly physiological biomechanical characteristics at both operative
      and adjacent spinal segments in vitro, indicating an excellent clinical potential
      for cervical artificial disc replacement.

PMID- 15739533
TI  - Cervical spine chordoid meningioma. Case report.
AB  - Chordoid meningiomas are a rare but increasingly recognized subtype of
      meningioma. Although some cases have been associated with systemic symptoms, in
      many instances the clinical features are indistinguishable from those associated
      with other subtypes of meningioma. Given the prognostic significance of the
      diagnosis of chordoid meningioma, careful consideration should be given to the
      diagnosis during histological assessment. The authors describe a rare case of
      chordoid meningioma in the cervical spinal region.

PMID- 15739534
TI  - En bloc resection of multilevel cervical chordoma with C-2 involvement. Case
      report and description of operative technique.
AB  - Chordomas are locally aggressive neoplasms with an extremely high propensity to
      recur locally following resection, despite adjuvant therapy. This biological
      behavior has led most authors to conclude that en bloc resection provides the
      best chance for the patient's prolonged disease-free survival and possible cure.
      The authors present a case of an extensive upper cervical chordoma treated by en
      bloc resection, reconstruction, and long-segment stabilization. Total
      spondylectomy of C2-4 with sacrifice of the right C2-4 nerve roots and a segment
      of the right vertebral artery was performed. The inherent anatomical complexities
      of en bloc resection in the upper cervical spine are discussed. To the authors'
      knowledge, this represents the first report of an en bloc resection for multi
      level cervical chordoma.

PMID- 15739535
TI  - Central nervous system superficial siderosis following spinal surgery.
AB  - Superficial siderosis of the central nervous system is a rare progressive disease
      associated with hemosiderin deposition on the leptomeninges of the neuraxis. In
      addition to tumors and vascular lesions, dural sleeve pseudomeningoceles caused
      by brachial plexus avulsion injury may be the bleeding source in this disease.
      The authors describe a patient who underwent anterior cervical spine surgery for
      spinal cord compression due to the ossification of posterior longitudinal
      ligament. The operation was complicated by a dural tear and subsequent
      psedomeningocele formation. Nine years later, this patient developed superficial
      siderosis. The possible mechanisms involved in the development of superficial
      siderosis in this patient will be discussed.

PMID- 15739536
TI  - Subarachnoid pressure-dependent change in syrinx size in a patient with
      syringomyelia associated with adhesive arachnoiditis. Case report.
AB  - The pathophysiology of syringomyelia is still not well understood. Current
      prevailing theories involve the assumption that cerebrospinal fluid (CSF) flows
      into the syrinx from the subarachnoid space through the perivascular space of
      Virchow-Robin. Reported here is the case of a patient with syringomyelia in which
      this course is clearly contradicted. This patient with a holocord syrinx
      associated with adhesive arachnoiditis was treated 3 years previously with
      insertion of a subarachnoid-peritoneal shunt and had recently experienced
      worsening myelopathy. On surgical exploration, the shunt system was functioning
      normally. The medium-pressure shunt valve was replaced with an adjustable valve
      with a higher closing pressure setting, thus increasing the CSF pressure in the
      subarachnoid space. Contrary to prevailing theories, this procedure markedly
      reduced the size of the syrinx. This case provides direct evidence that the
      syrinx size is inversely related to subarachnoid CSF pressure and supports the
      hypothesis that the pressure gradient across the spinal cord parenchyma is the
      force that generates syringes in syringomyelia.

PMID- 15739537
TI  - Topacheous gout as a rare cause of spinal stenosis in the lumbar region. Case
      report.
AB  - Despite the fact that gout is a common metabolic disorder, because its
      involvement of the axial skeleton is rare the diagnosis is often delayed, even in
      patients with long-standing gout who present with neurological deficits. The
      authors report the case of a woman with a history of extensive gout, emphasizing
      the clinical, radiological, and pathological features of a lumbar spinal
      stenosis.

PMID- 15739538
TI  - Thoracic aortic pseudoaneurysm after spine trauma in ankylosing spondylitis. Case
      report.
AB  - Ankylosing spondylitis (AS) is a rheumatic disease characterized by consolidation
      of the articulating surfaces and inflammation of the vertebral column. Because of
      its associated spine stiffness and secondary osteoporosis, patients with this
      disorder are at increased risk of vertebral fractures. Ankylosing spondylitis
      presents a significant challenge to spine surgeons because of its complex effects
      on the spine, extraarticular organ manifestations, and potential neurological and
      functional sequelae. Traumatic thoracic and lumbar spine injuries in this patient
      population may be associated with injury to the aorta either due to direct
      mechanical trauma or to blunt forces associated with the spine fracture. This
      complication and association is thought to be the result of pathophysiological
      changes that cause the aorta to become firmly adherent to the anterior
      longitudinal ligament. The authors present a case of AS in a patient with a
      thoracic spine fracture and in whom a delayed thoracic aortic pseudoaneurysm
      ruptured. To the best of the authors' knowledge, only five cases of this complex
      condition have been reported since 1980. Recognition of the potential for aortic
      injury in patients with AS should prompt early investigation of the aorta in
      cases involving numerous fractures and assist in surgical planning to avoid this
      lethal injury.

PMID- 15739539
TI  - Vertebral osteonecrosis associated with sarcoidosis. Case report.
AB  - Sarcoidosis is a systemic disease commonly affecting lung, skin, or eye.
      Sarcoidosis involved with osseous structures occurs in approximately 5% of
      patients, usually involving small bones. Spinal sarcoidosis is extremely rare.
      The authors report on a man in whom examination of a subclavicular lymph node
      biopsy specimen and its spinal involvement had established a diagnosis of
      sarcoidosis and who had undergone steroid therapy. Despite intensive conservative
      treatment, the authors observed progressive collapse of L-2 requiring spinal
      decompressive and reconstructive surgeries. Histological evaluation of the
      collapsed vertebra did not show the typical noncaseating granuloma; rather, the
      authors observed osteonecrosis of the entire L-2 structure without reactive
      cellular activities. Other potential diagnoses including infectious disease,
      metastatic spinal tumor, and osteoporotic vertebral collapse were excluded based
      on laboratory data, imaging studies, and pathological findings. Complete necrosis
      of the entire L-2 vertebra in this case can be considered as a rare clinical
      manifestation of spinal sarcoidosis. Because of osteopenia and systemic bone
      fragility, combined anterior-posterior spinal reconstructive surgery was
      performed to restabilize the severely damaged spine.

PMID- 15739540
TI  - A transsternoclavicular approach for the anterior decompression and fusion of the
      upper thoracic spine. Technical note.
AB  - The anterior approach is commonly used to reach the upper thoracic region to
      achieve decompression and stabilization; however, upper thoracic lesions are
      difficult to treat because of the regional anatomical structures, and this
      approach is associated with risks of complication. The authors evaluated the
      advantages of using a transsternoclavicular approach to aid in treating upper
      thoracic lesions. The procedure and surgery-related outcomes are discussed.

PMID- 15739541
TI  - Tophaceous gout of the atlantoaxial joint. Case illustration.

PMID- 15739542
TI  - Lumbar intradural metastasis of a primary carcinoid tumor of the lung. Case
      illustration.

PMID- 15739543
TI  - Surgical outcomes in 118 patients with Rathke cleft cysts.
AB  - OBJECT: Microscopic Rathke cleft cysts are a common incidental autopsy finding,
      but some Rathke cleft cysts can become sufficiently large to cause visual
      impairment, hypothalamic-pituitary dysfunction, and headaches. In this study
      patients were evaluated pre- and postoperatively to ascertain the clinical
      significance of surgical intervention on endocrine and visual improvement.
      Factors correlated with cyst recurrence were also evaluated. METHODS: A
      retrospective analysis was conducted in 160 patients with Rathke cleft cysts who
      were treated between 1984 and 1995 and completed at least a 5-year follow-up
      period. Of these 160 patients, 118 initially exhibited symptoms of visual
      impairment or endocrine dysfunction, became symptomatic during the follow-up
      period, or were found to have cyst enlargement. These 118 patients underwent
      transsphenoidal surgery. Forty-two patients with incidental lesions that
      demonstrated no growth on magnetic resonance (MR) images were followed up without
      an operation. Complete resection, as observed on MR images 3 months
      postoperatively, was obtained in 114 (97%) of 118 patients. Vision improved
      postoperatively in 57 (98%) of 58 patients. Hypogonadism improved in 11 (18%) of
      62 patients, growth hormone deficiency resolved in 14 (18%) of 78 patients, and
      hypocortisolemia resolved in one (14%) of seven patients. Twenty-two patients
      (19%) began to exhibit symptoms of diabetes insipidus, which had not been present
      preoperatively. The total 5-year recurrence rate was 18% (21 of 118 patients),
      with 12 patients requiring a repeated operation. Surgical and pathological
      factors that were found to be statistically associated with recurrence were the
      use of a fat and/or fascial graft for closure (p < 0.01) and the presence of
      squamous metaplasia in the cyst wall (p < 0.01). The extent of resection of the
      cyst wall was not associated with an increased rate of recurrence. In 42 (69%) of
      61 patients the incidental cysts did not progress on imaging studies or
      clinically. CONCLUSIONS: This is the largest series of patients with symptomatic
      Rathke cleft cysts who received operative intervention and participated in the
      longest postoperative follow up reported in the literature. The high recurrence
      rate (18%) supports the theory that a relationship exists between a symptomatic
      Rathke cleft cyst and craniopharyngioma. Improvements in visual and endocrine
      dysfunction can be expected after surgical decompression of the optic apparatus
      and the hypothalamic-pituitary axis.

PMID- 15739544
TI  - Risk factors for ischemic lesions following aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: The aim of this study was to test whether enoxaparin treatment (40 mg
      subcutaneously once daily) reduces the risk of cerebral infarction after
      subarachnoid hemorrhage (SAH) and to investigate predictive risk factors for
      permanent ischemic lesions visible on follow-up computerized tomography (CT)
      scans obtained 3 months after SAH. METHODS: After undergoing surgery for a
      ruptured aneurysm, 170 patients were randomized in a prospective, double-blind,
      placebo-controlled trial to test the effect of enoxaparin on the occurrence of
      ischemic lesions, which were demonstrated on follow-up CT scans available for 156
      patients. The presence of lesions correlated highly with an impaired outcome, as
      assessed using both the Glasgow Outcome and modified Rankin Scales (p < 0.01).
      Lesions occurred in 101 (65%) of the 156 patients. In half of the patients (51
      patients) no lesion was visible on the CT scan obtained on the 1st postoperative
      day in 51 patients. On univariate analysis, the presence of lesions at 3 months
      post-SAH was not associated with enoxaparin treatment but did correlate with
      several clinical, radiological, and prehemorrhage variables. Significant
      independent risk factors for lesions consisted of an impaired initial clinical
      condition (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.03-6.73), amount
      of subarachnoid blood (OR 6.51, 95% CI 2.27-18.65), nocturnal occurrence of SAH
      (that is, between 12:01 a.m. and 8:00 a.m.; OR 4.32, 95% CI 1.28-14.52), fixed
      symptoms of delayed ischemia (OR 5.21, 95% CI 1.02-26.49), duration of temporary
      artery occlusion during surgery (OR 1.66 per minute, 95% CI 1.20-2.31), and body
      mass index (OR 1.13/kg/m2, 95% CI 1.01-1.28). CONCLUSIONS: The presence of
      ischemic lesions can be predicted by the severity of bleeding, delayed cerebral
      ischemia, excess weight, duration of temporary artery occlusion, and occurrence
      of nocturnal aneurysm rupture.

PMID- 15739545
TI  - Neurosurgical workforce trends in the United States.
AB  - OBJECT: The purpose of this study was to evaluate the US neurosurgery workforce
      by reviewing journal recruitment advertisements published during the past 10
      years. METHODS: The number of available academic and private neurosurgical staff
      positions was determined based on recruitment advertisements in the Journal of
      Neurosurgery and Neurosurgery for the 10-year period from 1994 to 2003.
      Advertisements were evaluated for practice venue, subspecialization, and
      location. The numbers of active neurosurgeons and graduating residents also were
      reviewed. The number of advertised neurosurgical positions increased from 141.6
      +/- 38.2 per year from 1994 through 1998 to 282.4 +/- 13.6 per year from 1999
      through 2003 (mean +/- standard deviation, p < 0.05). The mean number of academic
      positions increased from 50.6 +/- 11.1 to 95 +/- 17.5 (p < 0.05), and the mean
      number of private positions rose from 91 +/- 30.4 to 187.4 +/- 6.8 (p < 0.05).
      Subspecialty positions represented a mean of only 15.6 +/- 5% per year during the
      first time period and 18.8 +/- 3% per year in the second period (p = 0.22), and
      therefore the majority of positions advertised continued to be those for
      generalists. The number of practicing neurosurgeons declined after 1998, and by
      2002 it was less than it had been in 1991. The numbers of incoming and
      matriculating residents during the study period were static. CONCLUSIONS: The
      number of recruitment advertisements for neurosurgeons during the last 5 years
      has increased significantly, concomitant with a severe decline in the number of
      active neurosurgeons and a static supply of residents.

PMID- 15739546
TI  - Resection of brain metastases previously treated with stereotactic radiosurgery.
AB  - OBJECT: To date, no report has been published on outcomes of patients undergoing
      resection for brain metastases who were previously treated with stereotactic
      radiosurgery (SRS). Consequently, the authors reviewed their institutional
      experience with this clinical scenario to assess the efficacy of surgical
      intervention. METHODS: Sixty-one patients (each harboring three or fewer brain
      lesions), who were treated at a single institution between June 1993 and August
      2002 were identified. Patient charts and their neuroimaging and pathological
      reports were retrospectively reviewed to determine overall survival rates,
      surgical complications, and recurrence rates. A univariate analysis revealed that
      patient preoperative recursive partitioning analysis (RPA) classification,
      primary disease status, preoperative Karnofsky Performance Scale score, type of
      focal treatment undergone for nonindex lesions, and major postoperative surgical
      complications were factors that significantly affected survival (p < or = 0.05).
      In contrast, only the RPA class and focal (conventional surgery or SRS) treatment
      of nonindex lesions significantly (or nearly significantly) affected survival in
      the multivariate analysis. Major neurological complications occurred in only 2%
      of patients. The median time to distant recurrence after resection was 8.4
      months; that to local recurrence was not reached. The overall median survival
      time was 11.1 months, with 25% of patients surviving 2 or more years.
      Conventional surgery facilitated tapering of steroid administration. Conclusions.
      The complication, morbidity, survival, and recurrence rates are consistent with
      those seen after conventional surgery for recurrent brain metastases. Our results
      indicate that in selected patients with a favorable RPA class in whom nonindex
      lesions are treated with focal modalities, surgery can provide long-term control
      of SRS-treated lesions and positively affect overall survival.

PMID- 15739547
TI  - Improvement of bilateral motor functions in patients with Parkinson disease
      through the unilateral intraputaminal infusion of glial cell line-derived
      neurotrophic factor.
AB  - OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has demonstrated
      significant antiparkinsonian actions in several animal models and in a recent
      pilot study in England in which four of five patients received bilateral
      putaminal delivery. In the present study the authors report on a 6-month
      unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson
      disease (PD). METHODS: Patients with PD in a functionally defined on and off
      state were evaluated 1 week before and 1 and 4 weeks after intraputaminal
      catheter implantation in the side contralateral to the most affected side. Each
      patient was placed on a dose-escalation regimen of GDNF: 3, 10, and 30 microg/day
      at successive 8-week intervals, followed by a 1-month wash-out period. The
      Unified Parkinson's Disease Rating Scale (UPDRS) total scores in the on and off
      states significantly improved 34 and 33%, respectively, at 24 weeks compared with
      baseline scores (95% confidence interval [CI] 18-47% for off scores and 16-51%
      for on scores). In addition, UPDRS motor scores in both the on and off states
      significantly improved by 30% at 24 weeks compared with baseline scores (95% CI
      15-48% for off scores and 5-61% for on scores). Improvements occurred
      bilaterally, as measured by balance and gait and increased speed of hand
      movements. All significant improvements of motor function continued through the
      wash-out period. The only observed side effects were transient Lhermitte symptoms
      in two patients. CONCLUSIONS: Analysis of the data in this open-label study
      demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF
      infusion. Unilateral administration of the protein resulted in significant,
      sustained bilateral effects.

PMID- 15739548
TI  - Percutaneous retrogasserian glycerol rhizotomy for patients with idiopathic
      trigeminal neuralgia: a prospective analysis of factors related to pain relief.
AB  - OBJECT: The goal of this study was to analyze prospectively factors associated
      with facial pain outcomes after percutaneous retrogasserian glycerol rhizotomy
      (PRGR) for patients with medically unresponsive idiopathic trigeminal neuralgia.
      METHODS: Between July 1999 and December 2003, 98 patients underwent PRGR in the
      manner described by Hakanson. The mean patient age was 72.1 years and the average
      pain duration prior to PRGR was 8.6 years. Fifty patients (51%) had previously
      undergone surgery. In six patients (6%), the trigeminal cistern could not be
      defined and the procedure was aborted; six patients were lost to follow-up
      review. An excellent facial pain outcome was defined as the absence of facial
      pain without medications. Thirty-two (35%) of 92 patients either received no
      benefit (17 patients) or experienced recurrent pain (15 patients) and required
      additional surgery at a mean of 7.5 months after PRGR; the mean duration of
      follow-up review in the other 60 patients was 28.7 months (range 3-52 months).
      Including patients who did not receive a glycerol injection, the 1- and 3-year
      chances of an excellent facial pain outcome were 61 and 50%, respectively. A
      multivariate analysis of clinical and surgical factors showed that the facial
      pain exhibited on glycerol injection correlated with excellent facial pain
      outcomes (relative risk [RR] = 1.02; 95% confidence interval [CI] 0.26-1.77; p <
      0.01), whereas patients who experienced any constant pain less frequently had
      excellent outcomes (RR = 1.13; 95% CI 0.06-2.20; p = 0.04). Forty-six patients
      (53%) experienced either mild numbness/parathesias (39 patients) or dysesthesias
      (seven patients). New trigeminal deficits after PRGR were associated with
      excellent facial pain outcomes (RR = 1.25; 95% CI 0.56-1.93; p < 0.001).
      CONCLUSIONS: Percutaneous retrogasserian glycerol rhizotomy remains a good
      operation for patients with medically unresponsive trigeminal neuralgia who are
      considered poor candidates for posterior fossa exploration. Predictive factors
      for success include patients without any constant facial pain, patients with
      immediate facial pain during glycerol injection, and patients with new trigeminal
      deficits after PRGR.

PMID- 15739549
TI  - Bacterial meningitis caused by the use of ventricular or lumbar cerebrospinal
      fluid catheters.
AB  - OBJECT: In the present study the authors compared the incidence and risk factors
      for external drainage-related bacterial meningitis (ED-BM) by using ventricular
      and lumbar catheters. METHODS: A cohort of 230 consecutive patients with ED was
      evaluated. Cerebrospinal fluid samples were obtained daily for microbiological
      culture, and ED-BM was defined based on culture results in combination with
      clinical symptoms. The incidence of ED-BM was 7% in lumbar and 15% in ventricular
      drains. Independent risk factors included site leakage, drain blockage, and most
      importantly duration of ED. Despite a higher infection rate, ventricular
      catheters did not have a significant higher risk of infection after correcting
      for duration of drainage. CONCLUSIONS: Analysis of data in the present study
      showed that the incidence of ED-associated death is low (0.45%) in patients who
      do not receive continuous antibiotic prophylaxis during ED.

PMID- 15739550
TI  - Buenos Aires experience with the Neuroform self-expanding stent for the treatment
      of intracranial aneurysms.
AB  - OBJECT: The authors report their experience with the use of the Neuroform
      Microdelivery System for intravascular reconstruction. They assess the technical
      feasibility of the system, the efficacy of the combined application of stent and
      detachable coils, and the follow-up findings. METHODS: Fifty patients found to
      harbor a complex wide-necked intracranial aneurysm were selected for the study.
      Different strategies were chosen and the performance and technical success of the
      device were evaluated. Stent placement was recorded as optimal or suboptimal with
      respect to the stent position. Clinical and angiographic follow-up examinations
      were obtained. Forty-six patients with 48 intracranial aneurysms were treated,
      leading to a technical success rate of 92%. Forty-two lesions were located in the
      anterior circulation. In every case the dome/neck ratio was less than 2 and the
      mean aneurysm size in these patients was 8.8 mm. The most frequent clinical
      presentation was subarachnoid hemorrhage in 48% of cases. Stent placement was
      optimal in 81.2% of cases and suboptimal in 18.8%. In 31% of cases, the
      investigators encountered difficulties in placing the Neuroform stent. Clinical
      follow up was recorded in all patients and angiographic follow up was obtained in
      63%. There were no cases of repeated hemorrhage. In a single case in which only
      the stent was implanted progressive thrombosis was identified during the follow
      up period. The procedure-related morbidity and mortality rates were 8.6 and 2.1%,
      respectively. CONCLUSIONS: On the basis of the results, the authors conclude that
      the Neuroform self-expanding stent is a flexible and useful device that can be
      readily and safely maneuvered through tortuous intracranial vessels, enabling the
      endovascular treatment of complex wide-necked aneurysms. Early in the authors'
      experience, stent delivery presented difficulties; however, a second generation
      of devices has resolved this limitation. Although the early results are
      promising, the long-term benefit of this technique has to be proved by
      angiographic and clinical follow-up examinations.

PMID- 15739551
TI  - Characterization of genetically defined types of Charcot-Marie-Tooth neuropathies
      by using magnetic resonance neurography.
AB  - OBJECT: Charcot-Marie-Tooth (CMT) disease is a collection of related genetic
      disorders affecting peripheral nerves with an incidence of one in every 2500
      individuals. A diagnosis of CMT disease has classically relied on a medical
      history, examination, and measurement of nerve conduction velocities.
      Advancements in genetic testing and magnetic resonance (MR) imaging techniques
      may provide clinicians with a more precise diagnostic armamentarium. The authors
      investigated MR neurography as a possible method to characterize CMT subtypes.
      METHODS: The authors performed MR neurography to evaluate sciatic nerves in the
      mid-thigh area of seven patients with genetically defined subtypes of CMT, one
      patient with chronic inflammatory demylinating polyneuropathy, and one patient
      without neuropathy. The authors correlate their findings with normal nerve
      conduction velocities (NCVs) and present their results as a descriptive case
      series. Although MR neurography could not be used to distinguish subtypes of CMT
      disease on nerve area or fascicle number, it appears to characterize phenotypic
      features and disease progression noninvasively in patients with some subtypes.
      CONCLUSIONS: In conjunction with NCV measurements, MR neurography may be useful
      in the diagnosis of CMT neuropathies and in monitoring disease progression.

PMID- 15739552
TI  - A series of 397 peripheral neural sheath tumors: 30-year experience at Louisiana
      State University Health Sciences Center.
AB  - OBJECT: This is a retrospective review of 397 benign and malignant peripheral
      neural sheath tumors (PNSTs) that were surgically treated between 1969 and 1999
      at the Louisiana State University Health Sciences Center (LSUHSC). The surgical
      techniques and adjunctive treatments are presented, the tumors are classified
      with respect to type and prevalence at each neuroanatomical location, and the
      management of malignant PNSTs is reviewed. METHODS: There were 361 benign PNSTs
      (91%). One hundred forty-one benign lesions were brachial plexus tumors: 54
      schwannomas (38%) and 87 neurofibromas (62%), of which 55 (63%) were solitary
      neurofibromas and 32 (37%) were neurofibromatosis Type 1 (NF1)-associated
      neurofibromas. Among the brachial plexus lesions supraclavicular tumors
      predominated with 37 (69%) of 54 schwannomas; 34 (62%) of 55 solitary
      neurofibromas; and 19 (59%) of 32 NF1-associated neurofibromas. One hundred ten
      upper-extremity benign PNSTs consisted of 32 schwannomas (29%) and 78
      neurofibromas (71%), of which 45 (58%) were sporadic neurofibromas and 33 (42%)
      were NF1-associated neurofibromas. Twenty-five benign PNSTs were removed from the
      pelvic plexus. Lower-extremity PNSTs included 32 schwannomas (38%) and 53
      neurofibromas (62%), of which 31 were solitary neurofibromas and 22 were NF1
      associated neurofibromas. There were 36 malignant PNSTs: 28 neurogenic sarcomas
      and eight other sarcomas (fibro-, spindle cell, synovial, and perineurial
      sarcomas). CONCLUSIONS: The majority of tumors were benign PNSTs from the
      brachial plexus region. Most of the benign PNSTs in all locations were
      neurofibromas, with sporadic neurofibromas predominating. Similar numbers of
      schwannomas were found in the upper and lower extremities, whereas neurofibromas
      were more prevalent in the upper extremities. Despite aggressive limb-ablation or
      limb-sparing surgery plus adjunctive therapy, malignant PNSTs continue to be
      associated with high morbidity and mortality rates.

PMID- 15739553
TI  - A series of 146 peripheral non-neural sheath nerve tumors: 30-year experience at
      Louisiana State University Health Sciences Center.
AB  - OBJECT: This is a retrospective review of 146 surgically treated benign and
      malignant peripheral non-neural sheath tumors (PNNSTs). Tumor classifications
      with patient numbers, locations of benign PNNSTs, and surgical techniques and
      adjunctive treatments are presented. The results of a literature review regarding
      tumor frequencies are presented. METHODS: One hundred forty-six patients with 111
      benign and 35 malignant PNNSTs were treated between 1969 and 1999 at the
      Louisiana State University Health Sciences Center (LSUHSC). The benign tumors
      included 33 ganglion cysts, 16 cases of localized hypertrophic neuropathy, 12
      lipomas, 12 tumors of vascular origin, and 11 desmoid tumors. There were four
      each of lipofibrohamartomas, myositis ossificans, osteochondromas, and
      ganglioneuromas; two each of meningiomas, cystic hygromas, myoblastoma or
      granular cell tumors, triton tumors, and lymphangiomas; and one epidermoid cyst.
      The locations of benign PNNSTs were the following: 33 in the brachial plexus
      region, 39 in an upper extremity, one in the pelvic plexus, and 38 in a lower
      extremity. The malignant PNNSTs included 35 surgically treated carcinomas, 15 of
      which originated in the breast and nine in the lung. There were two melanomas
      metastatic to nerve and one tumor each that had metastasized from the bladder,
      rectum, skin, head and neck, and thyroid, and from a primary Ewing sarcoma. There
      was a single lymphoma that had metastasized to the radial nerve and one chordoma
      and one osteosarcoma, each of which had metastasized to the brachial plexus.
      CONCLUSIONS: There were more benign PNNSTs than malignant ones. Benign tumors
      were relatively equally distributed in the brachial plexus region and upper and
      lower extremities, with the exception of the pelvic plexus, which had only one
      tumor.

PMID- 15739555
TI  - Functional outcomes and survival in patients with high-grade gliomas in dominant
      and nondominant hemispheres.
AB  - OBJECT: The goal of this study was to investigate survival and functional
      outcomes in patients with high-grade intracranial astrocytomas as a function of
      the location of the lesion in the dominant or nondominant hemisphere (DH and NDH,
      respectively), and to suggest management strategies for such patients based on
      these data. METHODS: Data were collected from the Glioma Outcomes Project
      database, a longitudinal database of demographic, clinical, and outcome data for
      patients with high-grade intracranial gliomas. From the entire database of 788
      patients, a subset of all 280 right-handed patients with newly diagnosed,
      unilateral gliomas involving potentially eloquent cortex was selected as the
      sample population. Two cohorts were defined based on the location of the tumor in
      the right or left cerebral hemisphere. All other relevant demographic and
      clinical data were nearly identical between the cohorts. A Kaplan-Meier analysis
      was conducted to assess survival, and Karnofsky Performance Scale scores assigned
      at 6 and 12 months postoperatively were compared as a measure of functional
      outcome. The analysis demonstrated no difference in survival between patients
      with lesions in the DH and those with tumors in the NDH. Additionally, no
      statistically significant difference in functional outcomes was observed between
      the two groups. CONCLUSIONS: Laterality of high-grade gliomas is not an
      independent prognostic factor for predicting survival or functional outcome. The
      findings in this study demonstrate that fears of increased postoperative
      morbidity or mortality in otherwise resectable tumors of the DH are unfounded,
      and the authors therefore advocate that the surgeon's decision to operate be
      guided by validated outcome predictors and not biased by tumor lateralization.

PMID- 15739554
TI  - Neuroradiographic changes following convection-enhanced delivery of the
      recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma.
AB  - OBJECT: Convection-enhanced delivery (CED) is a novel method for delivering
      therapeutic agents to infiltrative brain tumor cells. For agents administered by
      CED, changes on magnetic resonance (MR) imaging directly resulting from catheter
      placement, infusion, and the therapeutic compound may confound any interpretation
      of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14
      patients with recurrent malignant glioma underwent CED of interleukin (IL) 13
      PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a
      truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in
      this cohort of patients. METHODS: Patients were treated in two groups: Group 1
      patients received IL13-PE38QQR before and after tumor resection; Group 2 patients
      received infusion only after tumor resection. Preoperative and postinfusion MR
      images were obtained prospectively at specified regular intervals. Changes were
      noted along catheter tracks on postresection MR images obtained in all patients.
      A simple grading system was developed to describe these changes. When MR imaging
      changes appeared to be related to IL1 3-PE38QQR, patients were followed up
      without instituting new antitumor therapy. CONCLUSIONS: As CED of therapeutic
      agents becomes more common, clinicians and investigators must become aware of
      associated neuroimaging changes that should be incorporated into toxicity
      assessment. We have developed a simple grading system to facilitate communication
      about these changes among investigators. Biological imaging modalities that could
      possibly distinguish these changes from recurrent tumor should be evaluated. In
      this study the authors demonstrate the challenges in determining efficacy when
      surrogate end points such as time to tumor progression as defined by new or
      progressive contrast enhancement on MR imaging are used with this treatment
      modality.

PMID- 15739556
TI  - Posterior petrous meningiomas: 82 cases.
AB  - OBJECT: The aim of this study was to discuss posterior petrous meningiomas--their
      classification, clinical manifestations, surgical treatments, and patient
      outcomes. METHODS: A retrospective analysis was performed in 82 patients with
      posterior petrous meningiomas for microsurgery. According to the anatomical
      relationship with the posterior surface of the petrous bone and with special
      reference to the internal auditory canal (IAC), posterior petrous meningiomas
      were classified into three types: Type I, located laterally to the IAC (28
      cases); Type II, located medially to the IAC, which might extend to the cavernous
      sinus and clivus (32 cases); and Type III, extensively attached to the posterior
      surface of the petrous bone, which might envelop the seventh and eighth cranial
      nerves (22 cases). Sixty-eight (83%) of 82 cases involved total resection. The
      rate of anatomical preservation of facial nerve was 97.5%, whereas the functional
      preservation rate was 81%. The rate of hearing preservation was 67%. All Type I
      tumors were completely resected, and the rate of anatomical preservation of
      facial nerve was 100% and functional preservation was 93%. Regarding Type II
      lesions, 75% of 32 cases involved total resection; the rate of anatomical
      preservation of facial nerve was 97% and functional preservation was 75%. For
      Type III lesions, 73% of 22 cases were totally resected. The rate of anatomical
      preservation of facial nerve in patients with this tumor type was 95%, whereas
      functional preservation was 73%. CONCLUSIONS: Clinical manifestations and
      surgical prognoses are different among the various types of posterior petrous
      meningiomas. It is more difficult for Types II and III tumors to be resected
      radically than Type I lesions, and postoperative functional outcomes are
      significantly worse accordingly. The primary principles in dealing with this
      disease entity include preservation of vital vascular and central nervous system
      structures and total resection of the tumor as much as possible.

PMID- 15739557
TI  - Surgery for intracranial meningiomas in the elderly: a clinical-radiological
      grading system as a predictor of outcome.
AB  - OBJECT: A grading system, called the Clinical-Radiological Grading System (CRGS),
      has been developed to standardize surgical indications in elderly patients
      harboring intracranial meningiomas. Patients with a score lower than 10 had a bad
      prognosis regardless of surgical treatment, those with a score between 10 and 12
      had a prognosis positively influenced by surgery, and those with a score higher
      than 12 had a good prognosis regardless of surgical treatment. The authors
      performed a prospective cross-sectional study to validate further the use of the
      CRGS as a clinical tool to orientate surgical decision making in elderly patients
      and to explore prognostic factors of survival. METHODS: From 1990 to 2000 the
      authors consecutively recruited and surgically treated 90 patients 70 years of
      age or older with neuroimaging findings of intracranial meningiomas and a
      preoperative evaluation based on the CRGS. The surgical mortality rate, which
      covers deaths within 3 months after surgical intervention, was 7.8%, and the 1
      year mortality rate was 15.6%. Female sex and a higher CRGS score were associated
      with a higher probability of survival. Among the different subset items of the
      CRGS score, no peritumoral edema for surgical survival and no concomitant
      diseases for 1-year survival provide the strongest predictive contribution, even
      if not at a statistically significant level. CONCLUSIONS: The CRGS score is a
      useful and practical tool for the selection of elderly patients affected by
      intracranial meningiomas as surgical candidates. A CRGS score higher than 10 and
      female sex are good prognostic factors of survival. whereas age is not a
      contraindication to surgery.

PMID- 15739558
TI  - Intraoperative power Doppler ultrasonography with a contrast-enhancing agent for
      intracranial tumors.
AB  - OBJECT: The goal of this study was to evaluate intraoperative power Doppler
      ultrasonography when used with a contrast-enhancing agent for operations on
      intracranial tumors. METHODS: Forty intracranial tumors were examined using power
      Doppler ultrasonography with a galactose microparticle-based ultrasonographic
      contrast-enhancing agent during operations on the brain. The tumors included 37
      intracranial neoplasms (14 gliomas, six meningiomas, three hemangioblastomas, two
      malignant lymphomas, three other primary neoplasms, nine metastatic tumors, and
      three nonneoplastic lesions). All patients also underwent computerized tomography
      and magnetic resonance imaging, and all but three of the patients underwent
      digital subtraction (DS) angiography. Before injection of the ultrasonographic
      contrast agent, intra- and peritumoral power Doppler flow signals were detected
      in 32 of the intracranial tumors. After the injection, the signals were enhanced
      in blood vessels around the tumors and in the tumor parenchyma in 36 tumors. The
      duration of contrast enhancement continued for 70 to 365 seconds (mean 251.8 +/-
      69 seconds) after the injection. Among the tumors, hemangioblastomas displayed
      particularly strong contrast enhancement. In these intracranial tumors, the echo
      signals obtained using contrast-enhanced power Doppler ultrasonography correlated
      with DS angiographic staining. Power Doppler ultrasonograms with the appropriate
      contrast agent provided better data on the precise real-time position of the
      tumors and their relationship to adjacent vessels than ultrasonograms obtained
      before the injection of the contrast agent. CONCLUSIONS: Intraoperative power
      Doppler ultrasonography performed using a contrast-enhancing agent can facilitate
      intraoperative real-time navigation and assessment of the intratumoral
      vasculature and peritumoral vessels, particularly for tumors having abundant
      vessels such as hemangioblastomas.

PMID- 15739559
TI  - Brain surface reformatted images for fast and easy localization of perirolandic
      lesions.
AB  - OBJECT: The goal of this study was to evaluate a novel form of brain surface
      representation that allows simple, reliable mapping of the surface neuroanatomy
      for the preoperative evaluation of the spatial relationship between a focal
      lesion and the precentral gyrus. METHODS: High-resolution three-dimensional (3D)
      magnetic resonance (MR) imaging data sets were postprocessed using a curved
      multiplanar reformatting technique to create brain surface reformatted (BSR)
      images. These BSR images were reconstructed in less than 5 minutes and
      demonstrated the entire central sulcus with adjacent surface structures in one
      view. Two experienced neuroradiologists determined the localization of lesions
      near the central sulcus in 27 patients on standard MR images in three orthogonal
      planes and on BSR images. In addition, these observers judged whether the lesions
      were easy or difficult to localize on standard MR and BSR images, and whether
      diagnoses based on these methods were certain or doubtful. Anatomical
      localization based on BSR images was compared with that based on functional MR
      (fMR) images or intraoperative mapping of motor function. The BSR images yielded
      a perfect concordance with the fMR images and intraoperative mapping (Cohen kappa
      1.0) and optimal diagnostic accuracy in localizing perirolandic lesions (both
      sensitivity and specificity were 100%). Localization was judged to be easy for 48
      of 54 diagnoses based on BSR images compared with 26 of 54 based on standard MR
      images. Diagnoses were assessed as certain for 52 cases based on BSR images and
      34 cases based on standard MR images. CONCLUSIONS: Brain surface reformatted
      imaging improves the diagnostic accuracy of standard anatomical MR imaging for
      localizing superficial brain lesions in relation to the precentral gyrus. The
      complementary use of this technique with standard two-dimensional imaging is
      supported by the fast and simple postprocessing technique and may provide useful
      information for preoperative surgical planning.

PMID- 15739560
TI  - Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in
      patients with brain trauma.
AB  - OBJECT: The aim of this study was to compare the effects of two different
      treatment protocols on physiological characteristics and outcome in patients with
      brain trauma. One protocol was primarily oriented toward reducing intracranial
      pressure (ICP), and the other primarily on maintaining cerebral perfusion
      pressure (CPP). METHODS: A series of 67 patients in Uppsala were treated
      according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a
      secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in
      Edinburgh were treated according to a protocol aimed primarily at maintaining CPP
      greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24
      hours and 30 mm Hg subsequently. The ICP and CPP insults were assessed as the
      percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and
      CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was
      assessed based on the slope of the regression line relating mean arterial blood
      pressure (MABP) to ICP. Outcome was analyzed at 6 months according to the Glasgow
      Outcome Scale (GOS). The prognostic value of secondary insults and pressure
      reactivity was determined using linear methods and a neural network. In patients
      treated according to the CPP-oriented protocol, even short durations of CPP
      insults were strong predictors of death. In patients treated according to the ICP
      oriented protocol, even long durations of CPP insult-mostly in the range of 50 to
      60 mm Hg--were significant predictors of favorable outcome (GOS Score 4 or 5).
      Among those who had undergone ICP-oriented treatment, pressure-passive patients
      (MABP/ICP slope > or = 0.13) had a better outcome. Among those who had undergone
      CPP-oriented treatment, the more pressure-active (MABP/ICP slope < 0.13) patients
      had a better outcome. CONCLUSION: Based on data from this study, the authors
      concluded that ICP-oriented therapy should be used in patients whose slope of the
      MABP/ICP regression line is at least 0.13, that is, in pressure-passive patients.
      If the slope is less than 0.13, then hypertensive CPP therapy is likely to
      produce a better outcome.

PMID- 15739561
TI  - Multimodal metabolic imaging of cerebral gliomas: positron emission tomography
      with [18F]fluoroethyl-L-tyrosine and magnetic resonance spectroscopy.
AB  - OBJECT: The purpose of this study was to determine the predictive value of
      [18F]fluoroethyl-L-tyrosine (FET)-positron emission tomography (PET) and magnetic
      resonance (MR) spectroscopy for tumor diagnosis in patients with suspected
      gliomas. METHODS: Both FET-PET and MR spectroscopy analyses were performed in 50
      consecutive patients with newly diagnosed intracerebral lesions supposed to be
      diffuse gliomas on contrast-enhanced MR imaging. Lesion/brain ratios of FET
      uptake greater than 1.6 were considered positive, that is, indicative of tumor.
      Results of MR spectroscopy were considered positive when N-acetylaspartate (NAA)
      was decreased in conjunction with an absolute increase of choline (Cho) and an
      NAA/Cho ratio of 0.7 or less. An FET lesion/brain ratio, an NAA/Cho ratio, and
      signal abnormalities on MR images were compared with histological findings in
      neuronavigated biopsy specimens. The FET lesion/brain ratio and the NAA/Cho ratio
      were identified as significant independent predictors for the histological
      identification of tumor tissue. The accuracy in distinguishing neoplastic from
      nonneoplastic tissue could be increased from 68% with the use of MR imaging alone
      to 97% with MR imaging in conjunction with FET-PET and MR spectroscopy.
      Sensitivity and specificity for tumor detection were 100 and 81% for MR
      spectroscopy and 88 and 88% for FET-PET, respectively. Results of histological
      studies did not reveal tumor tissue in any of the lesions that were negative on
      FET-PET and MR spectroscopy. In contrast, a tumor diagnosis was made in 97% of
      the lesions that were positive with both methods. CONCLUSIONS: In patients with
      intracerebral lesions supposed to be diffuse gliomas on MR imaging, FET-PET and
      MR spectroscopy analyses markedly improved the diagnostic efficacy of targeted
      biopsies.

PMID- 15739562
TI  - Limited efficacy of gene transfer in herpes simplex virus-thymidine
      kinase/ganciclovir gene therapy for brain tumors.
AB  - OBJECT: Low efficacy of gene transfer, transient gene expression, and toxicity of
      viral vectors are the major hurdles in successful anticancer gene therapy. The
      authors conducted in vitro (U87MG cell line) and in vivo (xenograft, tumor
      bearing rodent model) studies to address the stability of transduction by using
      the adenoassociated virus serotype-2 (AAV2)-thymidine kinase (TK) vector over
      time. METHODS: Standard methods for cell growth and a ganciclovir (GCV)
      cytotoxicity assay were applied. The AAV2-TK was infused into implanted tumors in
      athymic rats via convection-enhanced delivery (CED). Thymidine kinase expression
      was evaluated through immunohistochemical analysis, and the distribution volumes
      of the transduced tumors were calculated. Twenty-four hours following the viral
      infusions, animals were treated with GCV (50 mg/kg intraperitoneally every day
      for 10 days; six rats) or phosphate-buffered saline (six rats). A rapid decrease
      in TK expression over time was observed both in vitro and in vivo. A large volume
      of the tumor (up to 39%) was transduced with AAV2-TK following CED.
      Administration of GCV resulted in limited therapeutic effects (survival of 25.8
      compared with 21.3 days). CONCLUSIONS: Rapid elimination of TK expression from
      dividing tumor cells and focal transduction of the brain tumor were most likely
      responsible for the limited bystander effect in this approach. Immediate
      administration of GCV is crucial to assure maximal efficacy in the elimination of
      cancer cells. In addition, the complete or diffused transduction of a brain tumor
      with TK may be required for its total eradication.

PMID- 15739563
TI  - Diffusion tensor analysis of peritumoral edema using lambda chart analysis
      indicative of the heterogeneity of the microstructure within edema.
AB  - OBJECT: Histopathological studies indicate that cerebral edema associated with
      tumors (peritumoral edema) does not represent a single pathophysiological or
      clinical entity. In this study the authors investigated peritumoral edema by
      performing lambda chart analysis (LCA), a noninvasive technique that can be used
      to make visible and analyze apparent water diffusivity in tissues in vivo, and
      assessed the utility of LCA in differentiating high-grade gliomas from nonglial
      tumors. METHODS: The water diffusivity characteristics of peritumoral edema
      associated with four tumor groups-12 high-grade gliomas, five low-grade gliomas,
      11 metastatic tumors, and 15 meningiomas-were assessed in 43 patients by
      performing magnetic resonance imaging with the aid of a 3-tesla magnetic
      resonance imaging system. In all tumor groups, peritumoral edema exhibited
      greater trace values and reduced anisotropy compared with normal white matter.
      Edema associated with high-grade gliomas had significantly higher trace values
      than edema associated with the other three tumor groups, although the anisotropic
      angles of those groups were comparable. CONCLUSIONS: Lambda chart analysis
      identified two distinct types of peritumoral edema: edema associated with high
      grade gliomas and edema associated with low-grade gliomas or nonglial tumors. The
      apparent water diffusivity was significantly greater in high-grade gliomas,
      whereas the anisotropy in these lesions was comparable to that of edema in other
      tumors. These findings indicated that water movement in areas of edema,
      predominantly in the extracellular spaces, was less restricted in high-grade
      gliomas, a phenomenon that likely reflected the destruction of the extracellular
      matrix ultrastructure by malignant cell infiltration and consequently greater
      water diffusion. Although preliminary, this study indicates that LCA could be
      used as a clinical tool for differentiating high-grade gliomas and for evaluating
      the extent of cellular infiltration.

PMID- 15739564
TI  - Biological activity of adult cavernous malformations: a study of 56 patients.
AB  - OBJECT: Cerebral cavernous malformations (CCMs) have previously been considered
      as congenital and biologically static malformations. On the other hand, the
      potential for growth and de novo generation of CCMs have also been reported. It
      is therefore important to study the proliferative and neoangiogenetic capacity of
      these lesions. METHODS: The authors studied the surgical specimens of 56 CCMs (23
      deep and 33 superficial) obtained from adult patients. The proliferative activity
      of the endothelium and the neoangiogenetic capacity of these lesions were
      considered through immunohistochemical anaylsis of proliferating cell nuclear
      antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia
      inducible factor (HIF)-1alpha, and endoglin antibodies. Positive immunostaining
      of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases
      for MIB 1. The expression of Flk-1 was observed in the endothelium of 71% of the
      cases, for VEGF in 41%, for HIF-1 alpha in 48.1%, and for endoglin in 63.6% of
      the cases. The correlation of immunohistochemical and clinical data indicated
      that VEGF was expressed in significantly less deep-seated lesions when compared
      with superficial CCMs. Neither the expression of the proliferative markers nor
      the expression of the angiogenetic antibodies correlated with patient age at
      surgery, sex, or the number of recent prior hemorrhagic episodes in the patients.
      CONCLUSIONS: The CCMs from adult patients are active lesions exhibiting
      endothelial proliferation and neoangiogenesis. According to the data in this
      study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated
      CCMs and is not associated with recent prior hemorrhages.

PMID- 15739565
TI  - Optical coherence tomography: a new method to assess aneurysm healing.
AB  - OBJECT: Aneurysmal subarachnoid hemorrhage affects approximately 10/100,000
      people per year. Endovascular coil embolization is used increasingly to treat
      cerebral aneurysms and its safety and durability is rapidly developing. The long
      term durability of coil embolization of cerebral aneurysms remains in question;
      patients treated using this modality require multiple follow-up angiography
      studies and occasional repeated treatments. METHODS: Optical coherence tomography
      (OCT) is an emerging imaging modality that uses backscattered light to produce
      high-resolution tomography of optically accessible biological tissues such as the
      eye, luminal surface of blood vessels, and gastrointestinal tract. Vascular OCT
      probes in the form of imaging microwires are presently available--although not
      Food and Drug Administration-approved--and may be adapted for use in the cerebral
      circulation. In this study the authors describe the initial use of OCT to make
      visible the neck of aneurysms created in a canine model and treated with coil
      embolization. Optical coherence tomography images demonstrate changes that
      correlate with the histological findings of healing at the aneurysm neck and thus
      may be capable of demonstrating human cerebral aneurysm healing. CONCLUSIONS:
      Optical coherence tomography may obviate the need for subsequent follow-up
      angiography studies as well as aid in the understanding of endovascular tissue
      healing. Data in this study demonstrate that further investigation of in vivo
      imaging with such probes is warranted.

PMID- 15739566
TI  - Quantified aneurysm shape and rupture risk.
AB  - OBJECT: The authors investigated whether quantified shape or size indices could
      better discriminate between ruptured and unruptured aneurysms. METHODS: Several
      custom algorithms were created to quantifiy the size and shape indices of
      intracranial aneurysms by using three-dimensional computerized tomography
      angiography models of the brain vasculature. Data from 27 patients with ruptured
      or unruptured aneurysms were evaluated in a blinded fashion to determine whether
      aneurysm size or shape better discriminated between the ruptured and unruptured
      groups. Five size and eight shape indices were calculated for each aneurysm. Two
      tailed independent Student t-tests (significance p < 0.05) were used to determine
      statistically significant differences between ruptured and unruptured aneurysm
      groups for all 13 indices. Receiver-operating characteristic-area under curve
      analyses were performed for all indices to quantify the predictability of each
      index and to identify optimal threshold values. None of the five size indices
      were significantly different between the ruptured and unruptured aneurysms. Five
      of the eight shape indices were significantly different between the two lesion
      groups, and two other shape indices showed a trend toward discriminating between
      ruptured and unruptured aneurysms, although these differences did not reach
      statistical significance. CONCLUSIONS: Quantified shape is more effective than
      size in discriminating between ruptured and unruptured aneurysms. Further
      investigation will determine whether quantified aneurysm shape will prove to be a
      reliable predictor of aneurysm rupture.

PMID- 15739567
TI  - Combined inhibition of vascular endothelial growth factor and platelet-derived
      growth factor signaling: effects on the angiogenesis, microcirculation, and
      growth of orthotopic malignant gliomas.
AB  - OBJECT: The goal of this study was to determine the effects of SU6668, a
      polyvalent receptor tyrosine kinase inhibitor against vascular endothelial growth
      factor receptor-2, platelet-derived growth factor receptor-beta, and fibroblast
      growth factor-1 on tumor growth, angiogenesis, and microcirculation in an
      orthotopic malignant glioma model. METHODS: Fluorescently labeled C6 malignant
      glioma cells were implanted into a long-term cranial window, which had been
      prepared in nude mice. The animals were treated with intraperitoneal injections
      of SU6668 (75 mg/kg/day) immediately (five animals) or 7 days (five animals)
      following tumor implantation. Control mice received intraperitoneal injections of
      vehicle (50 microl dimethylsulfoxide) immediately (five animals) or 7 days (four
      animals) after tumor implantation. Tumor growth, angiogenesis, and
      microcirculation were assessed by performing intravital fluorescence
      videomicroscopy over a 14-day observation period. To assess the effects of SU6668
      on overall survival, C6 glioma cells were implanted stereotactically into the
      brains of 24 additional animals and treatment was initiated on Day 7. In both the
      immediate and delayed experimental setting, SU6668 treatment resulted in a
      significant reduction of total and functional tumor vessel densities (both p <
      0.05), reflecting a suppression of angiogenesis and impairment of tumor
      perfusion. As a consequence, tumor growth was significantly inhibited (p < 0.05).
      Histological analysis demonstrated reduced tumor growth and less mass effect on
      the adjacent brain of treated animals. The survival experiments confirmed the
      importance of our results in that survival was significantly prolonged following
      SU6668 therapy (p < 0.05). CONCLUSIONS: Targeting of multiple angiogenic
      signaling pathways by polyvalent tyrosine kinase inhibitors represents a
      promising strategy to interfere with the vascularization, microcirculation, and
      growth of angiogenesis-dependent tumors. This also applies to malignant gliomas,
      despite the uniqueness of the cerebral microenvironment and the singular
      pathobiology of this tumor entity.

PMID- 15739568
TI  - Rhabdoid meningioma occurring in an unrelated resection cavity with
      leptomeningeal carcinomatosis. Case report.
AB  - Rhabdoid meningioma (RM) is a recently described, aggressive variant of
      meningioma. The authors report a case of RM occurring in the resection cavity of
      an unrelated neurosurgical procedure, temporal lobectomy for intractable
      seizures. The patient presented with intractable headache 10 years after the
      temporal lobectomy. Imaging revealed a dura-based, uniformly enhancing lesion
      within the resection cavity. She underwent gross-total resection and the findings
      of the surgical pathological report were consistent with an RM, with a
      dramatically elevated MIB-1 index of approximately 50%. The patient's clinical
      course was complicated by severe pain and communicating hydrocephalus secondary
      to rapid dissemination of malignant cells throughout the CSF pathways. Despite
      aggressive measures, including tumor resection, ventriculoperitoneal shunt
      placement, and the initiation of conventional radiation therapy, the ensuing
      leptomeningeal carcinomatosis proved to be rapidly fatal.

PMID- 15739569
TI  - Multicentric pleomorphic xanthoastrocytoma in a patient with neurofibromatosis
      type 1. Case report and review of the literature.
AB  - The authors report an unusual case of multicentric pleomorphic xanthoastrocytoma
      (PXA) in a 36-year-old woman with neurofibromatosis Type 1 (NF1). Both lesions
      were diagnosed as PXA but demonstrated different neuroimaging features and very
      different outcomes. Although the occipital lesion was cured surgically, the
      cerebellar tumor recurred three times and underwent malignant transformation into
      an anaplastic oligodendroglioma. The authors discuss the causes of PXA and
      suggest that it could originate from common bipotential precursor cells with two
      phenotypes.

PMID- 15739570
TI  - Femoral nerve palsy secondary to traumatic pseudoaneurysm and iliacus hematoma.
AB  - The authors report a case of traumatic femoral nerve palsy caused by a
      pseudoaneurysm of the iliolumbar artery and a iliacus muscle hematoma. This case
      report details not only the classic history and physical findings seen in
      patients such as this one, but also illustrates an unusual source of the hematoma
      and a discussion of its treatment. A 20-year-old man was assaulted and presented
      to the authors's institution with a 1-week history of severe pain in the left
      anterior thigh and groin, weakness in the left quadriceps muscle, and numbness in
      the anterior thigh and medial distal leg. Imaging studies demonstrated a large,
      9.4 x 6.4 x 5.2-cm iliacus hematoma as well as a pseudoaneurysm originating from
      the left iliolumbar artery. The patient underwent angiographic embolization of
      the pseudoaneurysm followed by surgical evacuation of the hematoma. The
      embolization was performed before surgery to prevent any possible rebleeding from
      the pseudoaneurysm during evacuation of the hematoma. Femoral nerve palsy caused
      by traumatic iliacus hematoma is an infrequent diagnosis often missed because of
      its insidious presentation. In this case, embolization of the iliolumbar artery
      pseudoaneurysm followed by surgical evacuation of the hematoma resulted in a
      nearly full recovery of the femoral nerve as of the last follow-up examination.

PMID- 15739571
TI  - Tension pneumoventricle after placement of a ventriculoperitoneal shunt: a novel
      treatment strategy. Case report.
AB  - A case of pneumoventricle following insertion of a ventriculoperitoneal shunt for
      hydrocephalus is described. The pneumoventricle was associated with significant
      morbidity, which improved with treatment. The authors propose a rational
      treatment for this condition, which, as far as they know, has not previously been
      described. They also discuss potential mechanisms involved in the pathogenesis of
      pneumoventricle.

PMID- 15739572
TI  - Subdural cysticercosis mimicking a chronic subdural hematoma. Case illustration.

PMID- 15739574
TI  - The Mayo brothers and Harvey Cushing: a review of their 39-year friendship
      through their personal letters.
AB  - Mayo Clinic founders, William J. Mayo and Charles H. Mayo, and Harvey W. Cushing
      were among the most significant pioneers of modem American surgery. A review of
      their personal correspondence reveals a special relationship among these three
      individuals, particularly between William Mayo and Cushing. Their interactions
      within the Society of Clinical Surgery initiated their close personal and
      professional association, which would endure for 39 years. William Mayo strongly
      supported Cushing's efforts to develop the specialty of neurological surgery, and
      Cushing sought Mayo's advice in making important career-related decisions. Their
      supportive friendship and professional alliance remains an example for future
      generations of neurological surgeons.

PMID- 15739573
TI  - De novo fenestration of the optic nerve. Case illustration.

PMID- 15739575
TI  - Research on Parkinson disease.

PMID- 15739576
TI  - Spectroscopy and navigation.

PMID- 15739577
TI  - Brachial plexus injury.

PMID- 15739578
TI  - Quality management case studies in health service emergencies: SARS and wildland
      urban interface fires.
AB  - The province of British Columbia, Canada, experienced 2 major health emergency
      situations during 2003: severe acute respiratory syndrome (SARS) in early 2003
      and wildland-urban interface fires during the summer of 2003. The interface fires
      occurred within the boundaries of the Interior Health Authority, 1 of 5 health
      authorities responsible for the delivery of health services in their respective
      areas of the province. The British Columbia Center for Disease Control (BCCDC)
      managed the SARS crisis in the province. Both organizations subsequently
      conducted quality management reviews of their handling of these emergency
      situations. This article reports on the quality management review of health
      services delivery during the interface fires and explores the role of physicians
      during regional emergencies. A similar report was published in the Spring 2004
      edition of Quality Management in Health Care on the way SARS was managed at the
      BCCDC. This article also compares managing a foreseeable emergency situation,
      such as a wildland-urban interface fire, with managing the unknown, which
      describes the situation during the initial stages of SARS. The realities
      confronting the unknown, and the need to manage the situation such that learning
      and discovery environments are allowed to come into being and evolve rapidly, are
      discussed.

PMID- 15739579
TI  - A call for board leadership on quality in hospitals.
AB  - A national agenda for health care quality is unfolding but there is concern about
      inadequate progress on improving quality in hospitals. The 2003 Institute of
      Medicine report calls for transformational leadership in health care
      organizations to change systems and processes underlying quality. The key
      question is: Who will provide leadership in hospitals? A natural choice is the
      board of trustees on account of its legal responsibility for quality and its
      authority over medical staff and administration. This article describes several
      barriers to board leadership on quality and suggests strategies by which boards
      can lead the campaign for quality. Barriers include trustee ignorance, trustee
      insecurity, board inattention, poor board-physician communication, fragmented
      information on quality, traditional medical staff structure, lack of professional
      management of quality, and lack of investment. Strategies for hospital board
      leadership should include preparing to lead, self-education, visible
      participation in quality activities, activism, role clarification, increased
      informal dialogue with physicians, medical staff reform, creation of a quality
      management department, instituting high-quality standards, and external quality
      audit. Boards face a historic opportunity to transform hospital quality backed by
      a strong legal mandate.

PMID- 15739580
TI  - Pay for performance: an excellent idea that simply needs implementation.
AB  - Pay for performance cannot consist of a one-size-fits-all approach. Variation in
      quality and cost of care is best measured using a single "value" (quality/cost)
      score that is decomposed into component cost and quality for every health care
      encounter type. Economic incentives must be enough to focus the provider's
      attention on each score part. Tools exist that improve the overall "value" of
      health care. We need agreement on an overall pay for performance approach
      together with a toolbox (not an approved list) of scientifically validated tools
      that payers, providers, and consumers can choose to build the incentives needed
      for pay for performance.

PMID- 15739581
TI  - An introduction to critical paths.
AB  - A critical path defines the optimal sequencing and timing of interventions by
      physicians, nurses, and other staff for a particular diagnosis or procedure.
      Critical paths are developed through collaborative efforts of physicians, nurses,
      pharmacists, and others to improve the quality and value of patient care. They
      are designed to minimize delays and resource utilization and to maximize quality
      of care. Critical paths have been shown to reduce variation in the care provided,
      facilitate expected outcomes, reduce delays, reduce length of stay, and improve
      cost-effectiveness. The approach and goals of critical paths are consistent with
      those of total quality management (TQM) and can be an important part of an
      organization's TQM process.

PMID- 15739582
TI  - QMHC interview with Miles Jay Zaremski, JD.

PMID- 15739583
TI  - Introducing CDS President Ron Testa.

PMID- 15739584
TI  - Esthetic restoration of discolored primary incisors.
AB  - Restoring primary teeth can be a strenuous task for many dentists who would like
      to have an esthetic, easy-to-use and relatively quick restoration for children.
      But, the restoration of carious, fractured or discolored primary incisors gives
      the dentist the satisfaction of knowing that he/she has restored the smile and
      self-confidence of a growing child. This article describes a technique which is
      relatively easy and produces a beautiful outcome in a relatively short time. The
      author has used the technique in hundreds of children for over twenty-five years.
      Modifications in the technique have been made as newer materials and techniques
      have evolved.

PMID- 15739585
TI  - Has casual gone too far in your office?

PMID- 15739586
TI  - Ethical hash.

PMID- 15739587
TI  - Retirement not end of the road for Carl Gilmore.

PMID- 15739588
TI  - Remembering the dental drill.

PMID- 15739589
TI  - Shareholders or caregivers?

PMID- 15739590
TI  - Caloric intake versus temporal pattern of food intake.

PMID- 15739591
TI  - Effects of dietary restriction on age-related changes in the phospholipid fatty
      acid composition of various rat tissues.
AB  - BACKGROUND AND AIMS: Polyunsaturated fatty acids (PUFAs) are essential components
      of the cell lipid bilayer and are involved in membrane fluidity and normal
      functioning, but they are vulnerable to free radical attack. Given the role of
      oxidative stress in the aging process, age-related changes in phospholipid fatty
      acid (PLFA) composition in rat liver, kidney and heart were assessed in 3-, 12-
      and 24-month-old rats fed either ad libitum but only every other day, or daily
      but only 60% of the quantity normally consumed by age-matched controls. METHODS:
      Lipids were extracted and phospholipids (PLs) were separated using the solid
      phase extraction technique, then transesterified and assayed by gas-liquid
      chromatography. RESULTS: Saturated fatty acids (FAs) did not change significantly
      with age; mono- and bi-unsaturated FAs decreased in the liver and heart, and the
      ratio of the former to the latter increased in the liver, kidney and heart. PUFAs
      increased in the liver and heart. As regards individual FAs, 20:1(n-9) decreased
      in all organs, 14:1 and 18:1(n-7) increased in the kidney and heart, 18:1(n-9)
      increased in the kidney, 20:2(n-6), 18:2(n-6) and 22:5(n-3) decreased in the
      liver and heart, 20:3(n-6) decreased in the kidney and increased in the heart.
      The most abundant PUFAs, 20:4(n-6) and 22:6(n-3), either remained the same or
      increased with age. The N-9 family increased in the kidney, the N-7 family
      increased in the kidney and heart, the N-6 family decreased in all three organs,
      and the N-3 family increased in the liver and kidney. Dietary restriction (DR)
      significantly counteracted most of these changes, but changes in some FAs [20:2(n
      6) in the heart] were magnified by DR and may not be age-related. CONCLUSIONS:
      Most age-related changes (that occurred in the rat liver, kidney and heart and
      were counteracted by the two different types of DR) may be involved in the
      mechanism of aging.

PMID- 15739592
TI  - Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a
      community primary prevention study.
AB  - BACKGROUND AND AIMS: Vitamin D deficiency is a well-known risk for hip fracture,
      and vitamin D insufficiency is so frequent in the elderly that population-wide
      preventive intervention would be useful. The objective of the study was to
      evaluate the efficacy of vitamin D bolus on hip fracture incidence in elderly
      women. METHODS: All women aged > 65 years registered at Health District 20 of the
      Regione Veneto, Italy, were eligible for this quasi-experimental, prospective
      community intervention study. A vial containing 400,000 IU vitamin D2 (Ostelin
      800, Teofarma, Italy) was offered for oral administration to all women in the
      winters of 2000-2001 and 2001-2002. The only exclusion criteria for treatment
      were age and gender, and the control group included women who did not participate
      in the Health District initiative. Analysis of hip fracture incidence was carried
      out for 4 years, from 1999 to 2002. Patients with incident hip fracture were
      identified as soon as they were admitted to one of the 3 hospitals of the health
      district and interviewed regarding their participation in the vitamin D
      preventive intervention program. In 120 of the women (age range 68-90 years),
      serum concentrations of 25-OH vitamin D were measured from October to June, both
      before and 1 and 4 months after vitamin D administration. RESULTS: 23,325 and
      24,747 women received the vitamin D bolus during winters 2000-2001 and 2001-2002
      respectively, i.e. 45-47% of eligible women. The proportion of women who accepted
      the bolus declined with advancing age, from 50-55% in women aged 60-70 years to
      22-26% in those aged > 90 years. The two-year intervention on the community
      decreased the incidence of fracture by 10% (p = 0.050) in comparison with the
      previous two years. The age-adjusted risk reduction (RR) of hip fracture during
      2001 and 2002 in women who had received vitamin D, with respect to women who had
      not, decreased by 17% (p = 0.056) and 25% (p = 0.005) respectively. The RR was
      considerably greater and statistically significant over both 2001 and 2002 in the
      cohort aged > 75 years. 25-OH vitamin D concentrations, in the subset of women in
      whom it was measured, rose significantly (p < 0.0001) by 9 ng/ml over 4 months
      after administration. CONCLUSION: Despite several obvious limitations due to its
      nature, this study sufficiently documents that yearly vitamin D bolus
      supplements, given as primary prevention to elderly Caucasian women, may decrease
      the incidence of hip fracture. For its probable safety and excellent feasibility
      and cost-effectiveness, this primary intervention has a great potential for
      generalisability.

PMID- 15739593
TI  - Life-style habits and homocysteine levels in an elderly population.
AB  - BACKGROUND AND AIMS: Increased plasma total homocysteine (Hcy) is a known
      cardiovascular disease (CVD) risk factor, related to several components of the
      established CVD risk profile. Observational studies support the role of modifying
      life-style related risk factors such as diet, physical activity and alcohol
      consumption in CVD prevention. Regular physical activity protects against
      coronary artery disease, possibly through its role in controlling risk factors
      such as hypertension, diabetes mellitus and obesity, but also independently. The
      aim of our study was to test the hypothesis that there is an association between
      physical activity, life-style habits and plasma Hcy levels in an elderly
      population. METHODS: In this cross-sectional study, 423 males and females aged
      69.0 +/- 6.7 years completed an interview and laboratory examinations. Our main
      outcome measure was plasma levels of Hcy. RESULTS: Mean Hcy values were 10.5 +/-
      5.5 micromol/L (11.4 +/- 6.1 for males and 9.3 +/- 4.5 for females; p < 0.001).
      Smoking and BMI were not found to be associated with Hcy levels. Physically
      active subjects, as well as B vitamin supplement users, had significantly lower
      Hcy levels (p = 0.002 and p = 0.004, respectively). In a multiple linear
      regression model, the Hcy level was 10% higher amongst participants with a
      sedentary life-style, 17% higher amongst males, 1% higher for each one-year
      increment in age, and 10% higher amongst participants who used no B vitamin
      supplements. CONCLUSIONS: Any level of physical activity was found to be an
      independent life-style habit associated with a lower Hcy level in an elderly
      population. This study supports existing recommendations for elderly persons to
      maintain a physically active life-style.

PMID- 15739594
TI  - The effects of oral amino acid intake on ambulatory capacity in elderly subjects.
AB  - BACKGROUND AND AIMS: The combination of high prevalence of inactivity in the
      older population, and high risk of ill-health and disability associated with
      inactivity, suggests that interventions that are successful in increasing levels
      of activity may have a great impact on population health in later life. With
      advancing age, the risk of developing serious nutritional deficiencies also
      increases. This study was designed to assess the effects of dietary amino acid
      supplementation on effort tolerance in healthy elderly subjects with reduced
      physical activity. METHODS: Forty-four subjects (age > 65 years) with sedentary
      life-style and lower health-related quality of life were studied. Subjects, in an
      open-label fashion, received an oral amino acid mixture (AAM, 12 g/day)
      containing essential and non-essential amino acids for a 3-month period.
      Ambulatory dysfunction resulting in sedentary life-style was assessed by a 6-min
      walk test. A walking impairment questionnaire (WIQ) was used to evaluate self
      perceived ambulatory dysfunction. Maximal isometric muscular strength of the
      right hand was measured during isometric exercise by a handgrip dynamometer.
      RESULTS: The 6-min walk distance increased from 214.5 +/- 32 to 262.8 +/- 34.8 m
      (p < 0.001) after AAM treatment. The baseline scores on the three subscales of
      WIQ changed significantly during treatment: WIQ distance increased from 56.2 +/-
      12.9 to 66.3 +/- 12.8% (p < 0.001); WIQ speed from 52 +/- 12.6 to 69.2 +/- 14.8%
      (p < 0.001) and WIQ stairs from 74.4 +/- 22.6 to 94.2 +/- 25% (p < 0.001), as did
      maximal isometric muscular strength (16.6 +/- 2.4 vs 19.2 +/- 2.2 kg, p < 0.001).
      Changes in plasma glucose (+11 +/- 11 mg/dL), total cholesterol (0 +/- 39 mg/dL),
      HDL cholesterol (0 +/- 17 mg/dL), and triglycerides (-11 +/- 58 mg/dL) were not
      significant between baseline and AAM. CONCLUSIONS: An oral amino acid supplement,
      as used in this pilot study, improves ambulatory capacity and maximal isometric
      muscle strength in elderly subjects without affecting the main metabolic
      parameters. Amino acid supplementation may thus represent useful non
      pharmacological intervention to maintain physical fitness in these subjects.

PMID- 15739595
TI  - The effects of different levels of dietary restriction on neoplastic pathology in
      the male Sprague-Dawley rat.
AB  - BACKGROUND AND AIMS: The primary purpose of this study was to evaluate the
      effects of varied levels of dietary restriction (DR) on neoplastic pathologies in
      rodents at 58 and 110 weeks of age. METHODS: Male Sprague-Dawley (SD) rats were
      divided into four nutritional groups; an ad libitum (AL) control group, and three
      dietary restricted (DR) groups that were fed the NIH-31 diet reduced in amount by
      10, 25, and 40%. RESULTS: At 110 weeks of age, compared to AL rats, the incidence
      of benign tumors was significantly lower in all DR groups while primary tumors
      were significantly lower in the 10 and 40% DR groups; no malignant tumors were
      detected in the 10% DR group. Most defined mortalities were caused by neoplastic
      lesions. All levels of DR reduced the percentage of tumor-bearing animals, the
      incidence of skin tumors (combined), and the total number of tumors. Pituitary,
      skin, and pancreatic tumors were the most prolific lesions; pituitary and skin
      tumors were the most fatal. Compared to AL rats, the time to onset of skin and
      pancreatic tumors was longer in all of the DR groups. CONCLUSION: In many cases,
      the incidences of neoplastic lesions were similar among the DR groups, clearly
      indicating that the DR effect is not linear and that even a very low level of DR
      (10%) can have a significant effect on many important neoplastic lesions and
      tumor burden. The main effect of DR was to decrease the incidence of some
      neoplastic lesions and to increase the time to onset and/or decrease the
      progression of tumors, thereby increasing the 110-week survival rate of DR rats.

PMID- 15739596
TI  - Biochemical, immunological and enzymatic components of saliva in prolonged naso
      gastric-fed elderly patients.
AB  - BACKGROUND AND AIMS: We have previously shown that naso-gastric tube (NGT)-fed
      patients harbor pathogenic flora in their oropharynx. The purpose of this study
      was to examine comparatively the biochemical, immunological and enzymatic
      components of the saliva of these patients with that of orally-fed counterparts.
      METHODS: The study group consisted of 19 elderly NGT-fed patients and 18
      comparable patients on oral feeding. Unstimulated whole saliva was collected and
      analyzed according to accepted methods for sodium, potassium, chloride, uric
      acid, total protein, albumin, amylase, lysozyme, and immunoglobulins, IgM, IgG,
      IgA, as well as secretory IgA. RESULTS: None of the above tested salivary
      components significantly differed between the two groups. Only uric acid levels
      were significantly lower (50%, p < 0.05) in NGT-fed patients. CONCLUSIONS: Uric
      acid is the main antioxidant component of saliva and, as such, it may be related
      to pathogenic bacterial colonization of the oropharynx in NGT-fed patients, with
      the risk of aspiration pneumonia.

PMID- 15739597
TI  - Relationships of body mass index with blood pressure and serum cholesterol
      concentrations at different ages.
AB  - BACKGROUND AND AIMS: Only limited information has been available on the effects
      of age on the relationship between obesity and other atherosclerotic risk
      factors, such as blood pressure and serum lipids. The purpose of this study was
      to investigate the effects of age on the relationships of obesity with blood
      pressure and serum cholesterol concentrations. METHODS: A community-based cross
      sectional study was performed on 157,902 workers in Yamagata, Japan. Blood
      pressure and serum total and HDL cholesterol concentrations were measured, and
      body mass index (BMI) and atherogenic index were calculated. The correlations of
      BMI with blood pressure, serum cholesterol concentrations and atherogenic index
      in different age groups were compared. RESULTS: BMI showed significant positive
      correlations with systolic and diastolic blood pressures, serum total cholesterol
      level and atherogenic index, and showed a significant negative correlation with
      serum HDL cholesterol level. The relationships of BMI with systolic and diastolic
      blood pressures became weaker with advancing age in both men and women after 30
      and 40 years of age, respectively. The relationships of BMI with serum total
      cholesterol level and atherogenic index also became weaker with advancing age
      after 30 years of age in men and after 40 years of age in women. There was no age
      dependent tendency in the relationship between BMI and HDL cholesterol, however.
      The above age-dependent changes were more prominent in men than in women.
      CONCLUSION: The relationships of obesity with blood pressure, serum total
      cholesterol level and atherogenic index in the elderly are much weaker than in
      the young.

PMID- 15739598
TI  - Factors influencing prognosis of pneumonia in elderly patients.
AB  - BACKGROUND AND AIMS: Polymorbidity reduces the survival of elderly patients with
      pneumonia. The aim of the proposed study was to identify factors determining
      mortality in such patients. METHODS: From January 1, 1999 to December 31, 2001,
      2870 patients were admitted to the Clinic of Geriatric Medicine, Faculty of
      Medicine, Comenius University, Bratislava. From these, 199 patients treated for
      pneumonia (average age +/- SD 79.7 +/- 7.6 yr) were assigned to a retrospective
      study. 112 patients recovered and 87 died. The prognostic significance of the
      chosen factors was evaluated by comparing their incidence between the groups of
      surviving and non-surviving patients. RESULTS: Prognosis for patients with
      pneumonia is worsened significantly by: older age; immobilization syndrome;
      incontinence of urine and feces; presence of some clinical and laboratory
      characteristics at the time of diagnosis of pneumonia (respiratory insufficiency,
      absence of fever, leukocytosis); pneumonia acquired in hospital;
      immunosuppressive therapy and comorbid conditions (congestive heart failure,
      chronic renal insufficiency, anemia, hepatic, psychiatric and neoplastic
      diseases). According to multivariate analysis, the most significant mortality
      predicting characteristics were: immobilization (odds ratio (OR) 9.36; 95%
      confidence interval (CI) 3.92-22.33); congestive heart failure (OR 8.26; 95% CI
      3.08-22.14); immunosuppressive therapy (OR 7.47; 95% CI 2.54-21.98) and
      psychiatric diseases (OR 4.53; 95% CI 1.94-10.58). CONCLUSIONS: Patients with
      immobilization, congestive heart failure, immunosuppressive therapy, or
      psychiatric diseases run a high risk of death and require intensive medical care.

PMID- 15739599
TI  - Combined measurement of serum albumin and high-density lipoprotein cholesterol
      strongly predicts mortality in frail older nursing-home residents.
AB  - BACKGROUND AND AIMS: The aim of this study was to verify the hypothesis that a
      combined measurement of albumin and HDL-C might predict total mortality in
      institutionalized frail older residents. METHODS: Participants were 344 older
      subjects (272 F, 72 M), living in the "Istituto Riposo Anziani" (I.R.A.), a
      nursing-home located in Padova, North-east Italy. Functional status, comorbidity,
      and clinical chemistry parameters were evaluated at entry. All-cause mortality
      was evaluated after 2 and 4 years. The sample was divided into 4 groups by using
      the 50 degrees percentile of albumin and HDL-C as cut-off value. The mortality
      odds ratio (OR) was estimated by multivariate logistic regression analysis.
      RESULTS: Total mortality was 36.8% after 2 years and 51.8% after four years. A
      trend toward an increase in mortality from group 1 to 4 was observed (p for
      trend: 0.01). The OR for 2 and 4 years mortality was 3.83 (95% CI 1.86-7.58) and
      2.66 (95% CI 1.37-5.17), respectively, in group 4 compared with group 1, after
      adjustment for age, gender, number of chronic diseases, functional status, BMI,
      diabetes, dementia, stroke, CHD, CHF, hypertension, depression, COPD, and total
      cholesterol levels. CONCLUSIONS: Among frail older nursing-home residents, simple
      measurement of serum albumin and HDL-C levels may be useful in identifying
      varying degrees of frailty.

PMID- 15739600
TI  - Post-operative degree of mobilization at two weeks predicts one-year mortality
      after hip fracture.
AB  - BACKGROUND AND AIMS: Although several investigations have tested physical
      activity a few months or one year after hip fracture, only a few have assessed
      physical activity shortly after hip fracture. The aim of this study was to
      evaluate how physical function two weeks after hip fracture operation predicts 12
      month mortality. This was a prospective study of hip fracture patients with one
      year follow-up, carried out in Jyvaskyla Central Hospital in Finland. METHODS: In
      this study, there were 243 consecutive community-dwelling patients aged 65 or
      older, who were able to walk before hip fracture. Two weeks after operation,
      information was gathered on pre-fracture activities of daily living (ADLs) and
      instrumental activities of daily living (IADLs). Patients' ability to stand up,
      sit down and walk was assessed. The follow-up lasted 12 months. RESULTS: The best
      predictor for mortality after one year was inability to stand up, hazard ratio
      (HR) 4.64 (95% CI 2.11-10.18, p < 0.001). The corresponding HRs concerning
      inability to sit down were 4.52 (95% CI 2.10-9.72, p < 0.001), inability to walk
      2.39 (95% CI 1.20-4.78, p = 0.013), ADL score 1.43 (95% CI 1.16-1.76, p = 0.001)
      and IADL score 1.19 (95% CI 1.03-1.38, p = 0.017). These variables were age- and
      sex-adjusted. According to the multiple proportional hazard model there was only
      one variable with statistical significance, i.e., the pre-fracture ADL-score (p =
      0.025). CONCLUSION: Inability to stand up, sit down or walk two weeks after
      operation were the strongest predictors for mortality among operated hip fracture
      patients. We suggest that focus should be directed to verify if better survival
      might be achieved by more intensive rehabilitation immediately after the
      operation. The pre-fracture ADL-score appeared to be the only variable reaching
      statistical significance in the multiple proportional hazard model. This fact may
      reflect frailty and affect decisions concerning the rehabilitation program.

PMID- 15739601
TI  - Hand grip strength and incident ADL disability in elderly Mexican Americans over
      a seven-year period.
AB  - BACKGROUND AND AIMS: Little is known about muscle strength as a predictor of
      disability among older Mexican Americans. The aim of this study was to examine
      the association between hand grip strength and 7-year incidence of ADL disability
      in older Mexican American men and women. METHODS: A 7-year prospective cohort
      study of 2493 non-institutionalized Mexican American men and women aged 65 or
      older residing in five south-western states. Maximal hand grip strength test,
      body mass index, cognitive function, activities of daily living, self-reports of
      medical conditions (arthritis, diabetes, heart attack, stroke, cancer, hip
      fracture), and depressive symptoms were obtained. RESULTS: In a Cox proportional
      regression analysis, there was a linear relationship between hand grip strength
      at baseline and risk of incident ADL disability over a 7-year follow-up. Among
      non-disabled men at baseline, the hazard ratio of any new ADL limitation was 1.90
      (95% CI 1.14-3.17) for those in the lowest quartile, when compared with men in
      the highest hand grip strength quartile, after controlling for age, marital
      status, medical conditions, high depressive symptoms, MMSE score, and BMI at
      baseline. Among non-disabled women at baseline, the hazard ratio of any new ADL
      limitation was 2.28 (95% CI 1.59-3.27) for those in the lowest quartile, when
      compared with women in the highest hand grip strength quartile. CONCLUSIONS: Hand
      grip strength is an independent predictor of ADL disability among older Mexican
      American men and women. The hand grip strength test is an easy, reliable, valid,
      inexpensive method of screening to identify older adults at risk of disability.

PMID- 15739602
TI  - Recombinant activated factor VII therapy in acquired hemophilia of the elderly.
AB  - Acquired hemophilia is a life-threatening condition associated with a high
      mortality, occurring mainly in elderly patients. We report on a 92-year-old male,
      administered two courses of 90 microg kg(-1) of recombinant activated factor VII
      (rFVIIa) due to failure of human factor VIII (FVIII) therapy, without side
      effects nor evidence of thrombotic complications. Despite the bleeding being
      completely under control, the patient died on day 11 of acute respiratory failure
      due to pneumonia. This case confirms previous reports on the complexity and
      severity of this disorder, showing that rFVIIa is an effective and safe agent for
      achieving hemostasis even in elderly patients with a FVIII inhibitor.

PMID- 15739603
TI  - Thyroid storm as precipitating factor in onset of coma in an elderly woman: case
      report and literature review.
AB  - Thyroid storm is an uncommon but life-threatening manifestation of
      hyperthyroidism which, unless appropriately treated by combined therapy, causes
      30-60% of deaths in hospitalized patients. Mental deterioration leading to apathy
      and eventually coma is a rare clinical presentation of this pathology, frequently
      observed in the elderly. We present the case of a 77-year-old hypertensive woman
      who was hospitalized for fast onset of coma, probably due to the unusual
      combination of a hypernatremic hyperosmolar state and an unexpected thyroid storm
      (TS). Although not definitely ascertained, the possible etiology was the
      hyperthyroid phase of chronic autoimmune thyreopathy (Hashitoxicosis). Notably,
      the significant adjunctive role of thyroid hyperfunction in the pathogenesis of
      coma was confirmed by the fact that, although metabolic abnormalities were
      overcome, complete and satisfactory recovery of the patient's mental and physical
      condition occurred only with normalization of thyroid hormones by antithyroid
      treatment. Our case highlights the importance of properly evaluating thyroid
      function in elderly patients who show a sudden progressive impairment in their
      mental condition, for early detection of potentially fatal conditions such as
      thyroid storm or myxedematous coma.

PMID- 15739604
TI  - Creating a critical mass.

PMID- 15739605
TI  - Recycle your mobile phone for tsunami relief.

PMID- 15739606
TI  - Remember our lost midwife colleagues.

PMID- 15739607
TI  - TPM/UNICEF tsunami appeal.

PMID- 15739608
TI  - Caring for mama and pikinini in Papua New Guinea.

PMID- 15739609
TI  - On mission with Medecins Sans Frontieres.

PMID- 15739610
TI  - Working independently in Spain.

PMID- 15739611
TI  - Contraception education in Brazil.

PMID- 15739612
TI  - Improving the birthing environment (Part 2).

PMID- 15739613
TI  - Midwives and change.

PMID- 15739614
TI  - Deconstructing prophylaxis (part 2).

PMID- 15739615
TI  - Midwifery basics: postnatal care. Post-operative care following caesarean.

PMID- 15739616
TI  - Let's ban water torture.

PMID- 15739617
TI  - Replicon cell culture system as a valuable tool in antiviral drug discovery
      against hepatitis C virus.
AB  - Discovery of potential therapeutics against hepatitis C virus (HCV) infection has
      been hampered in the past decade by the inability to grow this virus in tissue
      culture and by the lack of robust small animal models. This situation has been
      improved by the recent development of a selectable HCV replicon cell culture
      system. For the first time, drug discovery scientists are able to screen large
      compound collections using the replicon cell culture system to identify small
      molecules with the potential to inhibit HCV RNA replication. The replicon system
      has also been used to elucidate inhibitors' antiviral mechanism of action and to
      optimize antiviral potency. In this review, we will summarize the recent
      development of HCV replicon cell culture system and its use in anti-HCV drug
      discovery. The antiviral activities of promising lead compounds are also
      reviewed.

PMID- 15739618
TI  - New antiviral drugs, vaccines and classic public health interventions against
      SARS coronavirus.
AB  - Severe acute respiratory syndrome (SARS) is caused by one of two recently
      discovered coronaviruses. The virus is emergent from South East (SE) Asian
      mammals: either the civet cat, a related species or a rat species. The virus has
      a long incubation period and low reproduction number (R0 value) and hence the
      first outbreak in 2004 was controlled by hygiene and quarantine. However, the
      healthcare system was compromised and the economic cost was extremely high.
      Fortunately, the virus is easily cultivated in Vero E6 cells and therefore the
      search for new antivirals and vaccines was initiated within weeks of the
      discovery of the virus using classic techniques of cell culture and electron
      microscopy. Molecular diagnostics facilitated rapid and accurate diagnosis, a key
      factor in containing the outbreak. The broad-spectrum molecule ribavirin was used
      in SE Asia in infected patients alongside corticosteroids. In retrospect, many
      patients survived due to careful nursing. The only currently accepted
      intervention is interferon. Coronavirus replicon systems should facilitate rapid
      screening of new inhibitors and the complex mechanism of viral replication will
      ensure that drugs are developed against at least five molecular targets, in
      particular the viral protease.

PMID- 15739619
TI  - Current status of anti-SARS agents.
AB  - Severe acute respiratory syndrome (SARS) is a disease that has newly emerged in
      the 21st century, and is both severe and highly contagious. SARS first surfaced
      in late 2002 and spread within a few months from its origin in Guandong province,
      China, to more than 30 countries (World Health Organization, 2003). In this
      review, several antiviral substances shown to be active in vitro will be
      introduced and summarized in the order of the virus' replication steps; that is,
      binding to cellular receptor, fusion and entry to the cells, viral RNA
      replication and transcription, protein processing and so on. The possible
      clinical use of several synthetic peptides, including those that mimic the S
      binding domain, the HR2 fusion protein and SARS proteinase substrates, will be
      discussed. Monoclonal antibodies (Mabs) and established drugs, such as
      interferons and HIV proteinase inhibitors, are also discussed in relation to anti
      SARS clinical use.

PMID- 15739620
TI  - Colorimetric lactate dehydrogenase (LDH) assay for evaluation of antiviral
      activity against bovine viral diarrhoea virus (BVDV) in vitro.
AB  - A rapid and sensitive screening assay has been established for in vitro
      evaluation of antiviral compounds against bovine viral diarrhoea virus (BVDV),
      which is widely used as a surrogate for hepatitis C virus (HCV). The procedure is
      based on photospectrometrical assessment for the viability of virus-infected
      cells via extracellular leakage of lactic dehydrogenase (LDH). The level of LDH
      in culture supernatants of BVDV-infected Madin-Darby bovine kidney (MDBK) cells
      was significantly higher than those of mock-infected MDBK cells. Under optimized
      assay conditions, the LDH level was found to correlate well with the degree of
      viral replication. When the 50% effective concentrations (EC50s) of ribavirin,
      cyclosporine A and human interferon-alpha for BVDV replication were determined by
      the established LDH method and compared with those obtained by a conventional
      tetrazolium colorimetric (MTT) method, there was a complete correlation in EC50s
      between the two methods. Furthermore, a much higher ratio of background activity
      (noise) to sample activity (signal) could be achieved with the LDH method than
      with the MTT method, indicating that the present LDH assay permits a sensitive,
      rapid and reliable screening of compounds for their anti-BVDV activity and may be
      useful for the discovery of novel anti-HCV agents.

PMID- 15739621
TI  - Design of novel bioisosteres of beta-diketo acid inhibitors of HIV-1 integrase.
AB  - HIV-1 integrase (IN) is an attractive and validated target for the development of
      novel therapeutics against AIDS. Significant efforts have been devoted to the
      identification of IN inhibitors using various methods. In this context, through
      virtual screening of the NCI database and structure-based drug design strategies,
      we identified several pharmacophoric fragments and incorporated them on various
      aromatic or heteroaromatic rings. In addition, we designed and synthesized a
      series of 5-aryl(heteroaryl)-isoxazole-3-carboxylic acids as biological isosteric
      analogues of beta-diketo acid containing inhibitors of HIV-1 IN and their
      derivatives. Further computational docking studies were performed to investigate
      the mode of interactions of the most active ligands with the IN active site.
      Results suggested that some of the tested compounds could be considered as lead
      compounds and suitable for further optimization.

PMID- 15739622
TI  - Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort,
      1999--2003.
AB  - The objectives of our study were to describe the characteristics of a subset of
      patients who had been prescribed serum lactate in clinical practice within a
      large cohort of HIV-infected patients and to determine the factors associated
      with hyperlactataemia. Hyperlactataemia (> or =2 mmol/l) was found in 219 [29%
      (95% confidence interval: 25.3-31.7)] of the 768 HIV-infected participants. In
      multivariate analysis (logistical regression), an increased risk of
      hyperlactataemia was associated with increasing age, CD4 count <500/mm3,
      triglycerides >2.2 mmol/L, lipoatrophy and stavudine use. In a second model
      coding for the NRTI-based drug combinations, only those including stavudine were
      associated with an increased risk of hyperlactataemia. In a third model including
      exposure duration to NRTIs, we estimated a 20% increased risk of hyperlactataemia
      per year of exposure to didanosine or stavudine. The risk of hyperlactataemia
      could increase over time in patients treated with these drugs and is also closely
      associated with increased age, decreased CD4 count, lipodystrophy and increased
      plasma triglycerides. It could be proposed that patients having one or more of
      these risk factors undergo regular monitoring of plasma lactate and renal
      function to prevent lactic acidosis.

PMID- 15739623
TI  - The importance of nucleolar organizer regions in pediatric acute lymphoblastic
      leukemia.
AB  - The silver-staining of the nucleolar organizer regions (AgNORs) was performed in
      patients with acute lymphoblastic leukemia (ALL) to verify the role of cell
      proliferation in predicting complete remission and survival. Bone-marrow
      aspiration smears of 20 pediatric cases with ALL, were stained with argyrophilic
      method during the diagnosis, remission, and 3rd, 6th, 9th, and 12th months after
      remission. The mean NORs count (NORsc) and the mean of (nucleolar organizer
      regions surface/total nuclear surface x 100) value (NORss/TNs) for each case were
      calculated. At diagnosis, the NORsc and NORss/TNs value for the whole series were
      3.30+/-0.86 and 4.77+/-1.15, respectively. In complete remission, NORsc and
      NORss/TNs values were 1.23+/-0.20 and 3.45+/-0.87, respectively, and the
      differences were statistically highly significant (p < .001). The most important
      parameters of prognostic factors that effect diagnosis NORss/TNs and NORsc values
      were found to be FAB morphology and leukocyte count according to the multivariant
      analysis test. AgNORs analysis is a suitable method to assess cell proliferation
      in bone marrow aspirate and can predict complete remission, remission duration,
      and survival in pediatric ALL patients.

PMID- 15739624
TI  - Differential diagnosis of cholestasis following allogeneic hematopoietic stem
      cell transplantation in children: the contribution of serum bile acid levels in
      relation to other liver function tests.
AB  - Hepatic complications associated with cholestasis occur frequently in
      hematopoietic stem cell transplant recipients. Since bile acid seems to be a
      sensitive indicator of beginning cholestasis, the authors monitored total serum
      bile acid levels in addition to the standard liver function tests in 23
      recipients of allogeneic transplants between June 1999 and September 2000. The
      observations suggest that bile acid is an early and sensitive marker of hepatic
      GvHD but not as specific as bilirubin. For cholestasis in absence of hepatic GvHD
      bile acid seems to be more sensitive than bilirubin. Routinely monitoring of bile
      acid after hematopoietic stem cell transplantation is not indicated.

PMID- 15739625
TI  - Intestinal complications in children undergoing chemotherapy for mediastinal non
      Hodgkin's lymphoma.
AB  - Toxicities involving gastrointestinal tract are common in patients undergoing
      aggressive chemotherapy for cancer. However, it is uncommon to develop severe
      ulceration or perforation of the small intestine in absence of direct involvement
      of the bowel with the malignancy. The authors describe two children who developed
      severe gastrointestinal complications requiring surgical intervention following
      initial chemotherapy for non-Hodgkin's lymphoma. Both patients had no evidence of
      small bowel involvement by lymphoma on clinical staging.

PMID- 15739626
TI  - Temporary dysplastic hematological features due to iron deficiency in a case of
      Poland syndrome.
AB  - Poland syndrome has been sporadically associated with hematological conditions,
      primarily acute leukemias. The authors report a child with this syndrome
      coexisting with temporary hematological dysplasia due to iron deficiency. Further
      hematological evaluation failed to demonstrate malignancy. Because of its
      premalignant nature, in patients with Poland syndrome, hematological dysplastic
      features should be an indication for further investigation. However, in addition
      to the well-known hematological malignancies, treatable causes may be
      responsible.

PMID- 15739627
TI  - Cerebrospinal fluid soluble CD27 levels in children with non-Hodgkin lymphomas.
AB  - The authors investigated the diagnostic value of cerebrospinal fluid (CSF)
      soluble CD27 (sCD27) for leptomeningeal involvement of non-Hodgkin lymphomas
      (NHL). Cytospin slides were prepared from CSF samples of 64 children treated for
      NHL. sCD27 levels were determined by sandwich ELISA method using two CD27
      monoclonal antibodies. 8/194 (4.1%) samples were considered tumor-positive by
      cytology. Mean sCD27 values were 5.8 and 13.8 U/mL in tumor-negative and tumor
      positive samples, respectively (p =.18). 26/194 samples were false positive and
      2/194 false negative (cutoff: 7 U/mL) (sensitivity, 75 %; specificity, 86%;
      positive predictive value, 18.8%; negative predictive value, 98.8%; accuracy,
      85.6%). With these results, the value of adding sCD27 determination to the
      cytological CSF examination remains questionable.

PMID- 15739628
TI  - Combined chemotherapy and tracheobronchial stenting for life-threatening airway
      obstruction in a child with endobronchial non-Hodgkin lymphoma.
AB  - Endobronchial involvement in non-Hodgkin lymphoma is rare even in the presence of
      advanced disease. A 15-year-old boy presented with progressively worsening
      dyspnea with occasional hemoptysis for 1 week prior to admission. Three days
      later, he was intubated due severe dyspnea with complete atelectasis of the right
      lung. Fiberoptic bronchoscopy disclosed an endobronchial mass almost occupying
      the right main bronchus. He underwent partial resection of the endobronchial
      tumor with rigid bronchoscopy. An airway stenting was used in this patient
      because he had severe tracheal obstruction from the tumor. The compromised airway
      was alleviated by combined chemotherapy and tracheobronchial stenting.

PMID- 15739629
TI  - Malignant retroperitoneal paraganglioma: case report and review of the
      literature.
AB  - Paraganglioma is a rare neuroendocrine neoplasm observed in patients of all ages
      but it has not been characterized in children. The authors describe a
      retroperitoneal paraganglioma diagnosed by chance in an 11-year-old boy. Many
      aspects of retroperitoneal paraganglioma are still under investigation. The
      treatment of choice is radical resection. Surgery may be possible following
      chemotherapeutic debulking with cyclophosphamide, vincristine, and dacarbazine.
      131I-MIBG radiotherapy has proved increasingly useful in reducing the pain
      associated with disseminated disease and also in facilitating surgical resection
      in cases that appear inoperable. Conventional radiotherapy is purely palliative
      and used to reduce the pain of bone metastases.

PMID- 15739630
TI  - Megadose methylprednisolone for the treatment of patients with Evans syndrome.

PMID- 15739632
TI  - Blurred, blended or disappearing--the image of critical care nursing.

PMID- 15739631
TI  - Valproic acid induces differentiation of a supratentorial primitive
      neuroectodermal tumor.
AB  - In preclinical models the antiepileptic drug valproic acid induces
      differentiation of neoplastic cells, representing an evolving anticancer approach
      that takes into account that malignant cells resemble immature progenitor cells
      capable of terminal differentiation. The authors report on a child suffering from
      a relapsing supratentorial primitive neuroectodermal tumor that received valproic
      acid for epilepsy treatment over 7 months before the relapse. In contrast to the
      initial tumor, the relapsing tumor showed glial differentiation and low
      proliferation index. This is the first report of a relapsed supratentorial
      primitive neuroectodermal tumor that shows histologically confirmed signs of
      tumor cell differentiation induction.

PMID- 15739633
TI  - What is reasonable in organ donation?

PMID- 15739634
TI  - The identification of family members' contribution to patients' care in the
      intensive care unit: a naturalistic inquiry.
AB  - The admission of a patient to an intensive care unit (ICU) is recognized as being
      a stressful experience for their families. Many studies have focused on the needs
      of families within ICU, but few have highlighted the unique contribution that
      family members make towards patient care and recovery. Using a naturalistic
      approach, data were collected through observation, video recording, in-depth
      interviewing and reflective video analysis to explore the processes and factors
      underpinning families' contribution to patient care. The findings can be grouped
      into three themes: getting to know the patient through the family, family
      contribution to care and the nurses' role in supporting families of ICU patients.
      Families can have a very positive influence on the patient's care and recovery
      from ICU, but both the family members, and in turn the nursing staff, need to be
      supported appropriately if this valuable contribution to patient care is to be
      maximized and maintained.

PMID- 15739635
TI  - When the unreal becomes real: family members' experiences of cardiac arrest.
AB  - The aim of this study was to provide insight into family members' experiences
      related to cardiac arrest. Data were collected through semi-structured interviews
      with 17 family members approximately 5-34 months after the cardiac arrest of a
      relative. As the focus was on the family members' experiences seen from a
      holistic perspective, content analysis was chosen for the study. When the event
      occurred to the patient, family members realized the need for assistance and
      managed to initiate first actions. When the emergency medical service arrived,
      family members responded to stress and forgot their own needs. When the staff
      took over at the hospital, family members not only received sympathy but also
      encountered professional distancing. Because their experiences vary widely, the
      encounter has to be developed through a comforting, sympathetic and respectful
      dialogue in consideration for individuals' preferences.

PMID- 15739636
TI  - Relatives' experiences of critical care.
AB  - This exploratory study investigates relatives' overall experiences of the
      critical care environment and how staff perceived these experiences.
      Traditionally, research in Critical Care concentrated on patients' psychological
      well-being or relatives' immediate needs. There is little research that addresses
      the relative's overall experience of events. Critical Care Units are possibly the
      most daunting units in hospitals. Having a family member admitted to a Critical
      Care Unit could qualify as a traumatic-enough stressor to induce post-traumatic
      stress symptoms in relatives. A convenience sample of eight relatives and five
      staff participated in the study. The study used qualitative methods and drew on
      techniques of grounded theory. While staff perceived relatives' experiences
      accurately; issues arose, from both staff and relatives perspective, with regard
      to accurate dissemination of information. Further research into the communication
      processes used within Critical Care Units is required in addition to developing
      best practice in this area.

PMID- 15739637
TI  - The use of patient diaries in an intensive care unit.
AB  - Many patients experience posttraumatic stress disorder following a stay in
      intensive care; this can be due to a lack of recall of their stay. Retrospective
      patient diaries (n = 8) with follow-up have been used to try and help patients'
      recovery but have been found to be impersonal. Prospective diaries (n= 35) were
      implemented and trialled with follow-up at 2, 6 and 12 months postdischarge.
      Patients' and relatives' initial feedback regarding diaries is extremely
      positive. Benefits included better understanding of the events of the critical
      illness, helping with more realistic goal setting during the recovery period,
      improving communication within families through discussion of the diary and
      providing a source of comfort for the bereaved. More formal audit of these
      diaries is required and is currently being undertaken.

PMID- 15739638
TI  - Kinetic therapy positively influences oxygenation in patients with ALI/ARDS.
AB  - Acute respiratory distress syndrome (ARDS) is a fulminant form of respiratory
      failure, with diverse aetiology, despite technological advances in intensive care
      medicine; mortality rates remain 50-70%. Costs associated with the management of
      patients in intensive therapy unit (ITU) are very high; therefore, the
      requirement for those working in critical care to provide evidence-based practice
      is mandatory. One area of investigation is that kinetic therapy improves
      pulmonary complications in critically ill patients by positively influencing
      oxygenation and gaseous exchange. Whilst kinetic therapy does appear to be an
      effective therapy in ITU, there are inconsistencies in reported findings, and
      thus, clearly a need for further research into this innovative therapy to
      maximize its potential.

PMID- 15739639
TI  - [Scientific and practical conference with international participation on the
      Surgical Treatment of Wounds and Defects of Soft Tissues. Kyiv, Ukraine.
      Abstracts].

PMID- 15739641
TI  - Nursing on trial.
AB  - Nurses have reacted angrily to secret filming of poor quality care in two
      hospitals. But the Channel 4 documentary struck an uncomfortable chord with
      others in the profession.

PMID- 15739642
TI  - Self discovery.

PMID- 15739643
TI  - Meet Nurse Fi.

PMID- 15739644
TI  - The go-getter. Interview by Dina Leifer.

PMID- 15739645
TI  - Developing a paediatric asthma review pro forma.
AB  - BACKGROUND: Accurate record keeping can enhance patient care by promoting
      continuity and consistency of management, and aid evaluation of clinical
      practice. To improve paediatric asthma management, the paediatric respiratory
      team in a large district general hospital developed a pre-printed asthma review
      sheet (pro forma) for use at asthma follow-up clinics in the paediatric
      outpatient department. To assess the pro forma's effectiveness, the team examined
      the quality of clinical documentation during a retrospective audit of entries in
      the case notes of 100 patients, and compared it with that in 100 completed pro
      formas. The completed pro formas contained information on general progress,
      symptom severity and management of the child since the last medical review.
      CONCLUSION: The pro forma was shown to improve overall documentation. It not only
      aided the collection of relevant, clinically useful information, thereby helping
      clinicians to make decisions on management regimens, but it, also proved to be a
      valuable assessment tool for the management of chronic asthma in children.

PMID- 15739646
TI  - Chronic obstructive pulmonary disease and the NICE guideline.
AB  - This article covers the key priorities identified by the National Institute for
      Clinical Excellence (NICE) guideline for the management of chronic obstructive
      pulmonary disease (COPD) and examines the role of nurses in achieving these
      priorities for good care of patients with COPD.

PMID- 15739647
TI  - Mentoring learners in practice. Number 6. Building a rapport with the learner.

PMID- 15739648
TI  - My practice.

PMID- 15739649
TI  - Reach a wider audience.

PMID- 15739650
TI  - Causes of and treatment options for abnormal scar tissue.

PMID- 15739651
TI  - Measuring the impact of venous leg ulcers on quality of life.
AB  - OBJECTIVE: To identify health-related quality-of-life (HRQoL) issues in patients
      with venous leg ulcers, with the aim of generating items for a treatment outcome
      measure. METHOD: Thirty-eight patients with venous leg ulcers were interviewed by
      a psychologist using a semi-structured guide; they also completed a HRQoL
      questionnaire (modified Skindex). Data from the questionnaire were examined to
      explore the impact of venous leg ulcers on patients' lives. Interview transcripts
      were analysed using qualitative methods to identify additional venous leg ulcer
      specific HRQoL items. RESULTS: Skindex scores indicated that older patients had
      worse HRQoL (p<0.05), as did those with pain and non-healing ulcers. Ulcer
      duration and size did not correlate with HRQoL. Interviews revealed the following
      effects of ulceration: pain (80.5%); itching (69.4%); altered appearance (66.7%);
      loss of sleep (66.6%); functional limitation (58.3%); and disappointment with
      treatment (50%). Based on the interview transcripts, items were generated and
      discussed with an expert panel, with a view to including them in a venous leg
      ulcer-specific HRQoL questionnaire. CONCLUSION: Disease-specific HRQoL outcome
      measures should be considered when evaluating treatments for venous leg ulcers.

PMID- 15739652
TI  - Proteases and pH in chronic wounds.

PMID- 15739653
TI  - A pilot study to determine whether a static magnetic device can promote chronic
      leg ulcer healing.
AB  - OBJECTIVE: To determine if UlcerCare, a specialised self-securing static magnetic
      device, can promote the healing of chronic leg ulcers. METHOD: This double-blind
      placebo-controlled pilot study involved 26 patients with chronic leg ulcers,
      receiving care consistent with RCN guidelines, who were randomly allocated to
      receive either UlcerCare leg wrap (treatment) or an identical sham non-magnetic
      device (control). Wounds were assessed for 12 weeks at four weekly intervals
      using digital photography, Verge Videometer analysis and patient questionnaires
      to determine changes in ulcer size, level of pain and function. RESULTS:
      Statistically significant reductions in ulcer measurement were noted in the
      treatment group when compared with the placebo group. CONCLUSION: The results
      demonstrate a significant healing effect in the treatment group. A larger
      randomised controlled study is recommended to investigate the effects on ulcer
      associated pain and quality of life.

PMID- 15739654
TI  - Qualitative and quantitative evaluation of a new regimen for malignant wounds in
      women with advanced breast cancer.
AB  - OBJECTIVE: To investigate the experience of women with advanced breast cancer who
      have a malignant fungating wound and to test the benefits of a structured,
      evidence-based, management regimen, combined with psychosocial support. METHOD:
      Twelve women with advanced breast cancer were consecutively selected for
      inclusion in a four-week intervention. The patients were interviewed and the
      condition of the wounds was recorded before and after the intervention. RESULTS:
      Prior to the intervention, participants were anxious about seepage, bleeding and
      odour emanating from the wounds and were concerned these might be obvious to
      others. After the intervention, nine wounds (75%) showed an improvement, with
      increased granulation and epithelialisation and complete wound healing in one
      participant. Seepage was considerably reduced in 83% of cases and there was an
      average 75% reduction in dressing changes. The women's sense of well-being
      improved, as did their independence and self-confidence. CONCLUSION: A wound-care
      intervention built on evidence-based practice and psychosocial support resulted
      in an improvement in 75% of the wounds, and increased the women's sense of well
      being, independence and security.

PMID- 15739655
TI  - Information leaflets for venous leg ulcer patients: are they effective?
AB  - OBJECTIVE: To validate the usefulness of written information for patients with
      venous leg ulcers and test the hypothesis that patients who receive written
      information retain more knowledge than those who receive verbal information
      alone. METHOD: Twenty patients newly diagnosed with venous leg ulcers were
      recruited into this prospective trial. Patients were randomised either to the
      control group (given verbal information on their condition) or the intervention
      group (same verbal information and an information leaflet). The verbal
      information was in the same format as in the leaflet. Patients' knowledge of the
      condition was ascertained at an initial interview and at follow-up four to six
      weeks later. RESULTS: At follow-up both groups showed an overall improvement in
      knowledge, with no statistical difference between them. CONCLUSION: The results
      indicate there is limited value in providing information leaflets to this patient
      group, who were predominantly older patients with low levels of education. The
      relatively small sample size may explain the disappointing results. Further
      research may reveal a benefit of providing these leaflets to carers.

PMID- 15739656
TI  - Preventing the occurrence of pressure ulceration in hospitalised elderly
      patients.
AB  - OBJECTIVE: To determine which factors contribute to the development of pressure
      ulcers and to evaluate the role of topical agents in preventing their occurrence.
      METHOD: An observational, prospective survey covered 36 care of the elderly wards
      and involved 1121 patients at high or very high risk of pressure ulceration. The
      patients, of whom 667 (59.6%) received a gentle application of a topical agent to
      at-risk areas, were followed up for eight weeks. RESULTS: Of the patients, 15.7%
      developed a pressure ulcer. The use of a corpitolinol 60-based topical agent
      (Sanyrene/Corpitol) significantly reduced the incidence of pelvic pressure ulcers
      (p=0.04) when used with recognised prevention strategies. This was identified by
      undertaking a logistic regression analysis. The resulting odds ratio of 0.61
      indicates that the intervention helped to reduce the number of pressure ulcers by
      40%. CONCLUSION: The results of this observational study can provide a useful
      guide to the design of further randomised controlled trials.

PMID- 15739657
TI  - Effects of diabetes mellitus on wound healing: an update.

PMID- 15739658
TI  - A critical review of the literature on pressure ulcer aetiology.

PMID- 15739659
TI  - Recent advances in local anaesthesia.
AB  - This paper describes developments in the field of dental local anaesthesia.
      Recently introduced injectable agents, advances in the field of topical
      anaesthesia and new delivery systems are discussed.

PMID- 15739660
TI  - To open or to close space--that is the missing lateral incisor question.
AB  - Developmentally absent permanent maxillary lateral incisors may be associated
      with several problems. The decision whether to open or to close the space should
      involve the patient/parent, orthodontist and restorative dentist. To optimize
      function and aesthetics, space should be opened using fixed appliances to
      accommodate an appropriate prosthesis. Implant-retained crowns offer several
      advantages, although adhesive bridges are more appropriate in certain
      circumstances. Removable partial dentures may be necessary in some instances.
      Where space opening is not feasible, practical or desirable, any residual spacing
      can be closed using fixed appliances and the permanent maxillary canines modified
      to resemble lateral incisors.

PMID- 15739661
TI  - A review of gagging problems in dentistry: I. Aetiology and classification.
AB  - Some people have a pronounced gag reflex that can be a severe limitation to their
      ability to accept dental care and the clinician's ability to provide it. It can
      compromise all aspects of dentistry, from diagnostic procedures to active
      treatment and can be distressing for all concerned. Many techniques have been
      described that attempt to overcome the problem. Dentists will undoubtedly see
      patients with gagging problems and knowledge of a variety of management
      strategies is necessary to aid the delivery of dental care. This first paper
      looks at the background to gagging problems and their classification and
      categorization prior to clinical treatment. The second article will look at the
      clinical assessment of the patient presenting for dental treatment with a history
      of gagging problems. It will also review methods used to manage patients with
      gagging reflexes during dental treatment.

PMID- 15739662
TI  - The cognitive and social development of the child.
AB  - The social and psychological development of children from birth to adolescence is
      described using the framework of Jean Piaget's theory of cognitive development.
      This theory proposes that children's understanding of the world proceeds through
      four broad stages, with each stage demonstrating an increasingly sophisticated
      understanding of concepts and how they can be used. The relevance of this
      development for children's understanding of oral health, disease and dental care
      is discussed.

PMID- 15739663
TI  - An overview of bleaching techniques: 2. Night Guard Vital Bleaching and non-vital
      bleaching.
AB  - Night Guard Vital Bleaching (NGVB) or dentist-monitored bleaching technique is
      probably the most widely used bleaching technique because of its relative ease of
      use, low cost, safety and high success rate. There are many non-vital bleaching
      techniques available, all of which have one thing in common, usually a successful
      result in the procedure returning the discoloured tooth to its original colour
      and beyond that when required. This article will give an overview of various home
      bleaching techniques: materials and regimens used, bleaching procedure and
      treatment of side-effects. In addition, it will review various in-surgery and at
      home techniques used for bleaching non-vital teeth.

PMID- 15739664
TI  - Making the most of audit.
AB  - This article explores the steps in making the most of audits conducted in primary
      dental care. Audit is the principle method of measuring consistency in quality
      assurance systems and so is an essential part of clinical governance.

PMID- 15739665
TI  - [The Clinical Hospital "Coltea"--three centuries of existence].

PMID- 15739666
TI  - Minimally invasive parathyroidectomy.

PMID- 15739667
TI  - [Principles of esophageal repair in non-expansive corrosive esophageal
      strictures].

PMID- 15739668
TI  - [Benign esophageal strictures--outcomes of coloesophagoplasty in Surgical Clinic
      II Timisoara].
AB  - Esophagoplasty is obviously a proper choice of treatment; postoperative outcomes
      should be very good because of benign type of lesions, but morbidity-mortality
      are high due to the complexity of the intervention. Our purpose is to emphasize
      the utility of coloesophagoplasty like a very feasible surgical option, based to
      our short and long term outcomes. This paper relies on the retrospective analysis
      of all cases admitted to II-nd Surgical Clinic Timisoara in a 20 years period
      (1983-2002), having coloesophagoplasty for benign esophageal stenosis. There were
      performed 45 such interventions (16 men, 29 women); the mean age was 35.7 years
      (15-68 years). The pathology included postcaustic lesions (42 cases), peptic
      lesions (2 cases) and esophageal leiomyoma (1 case). Postoperative morbidity
      occurred in 22.6% of patients. The graft functionality was good and very good in
      86.6% of patients at discharge. Postoperative mortality was 6.6%.

PMID- 15739669
TI  - [Coloesophagoplasty, a choice operation for postcaustic esophageal stenosis].
AB  - OBJECTIVE: To evaluate the problems of approach, of technique and of care as a 20
      years experience demonstrates. MATERIAL AND METHOD: a retrospective study
      including 45 operated cases where the large-bowel served as reconstructive
      material (in 33 cases the transverse colon and in 12 cases right ileocolon).
      RESULTS: Healing was obtained in 42 patients. Early postoperative evolution
      presented: peritonitis caused by anastomotic leakages--2 cases, hemoperitoneum--2
      cases, cervical fistula --1 case, wound infection--6 cases, evisceration--1 case,
      acute respiratory failure--6 cases. Cervical anastomosis reconstruction for late
      stenosis--1 case. There were 2 postoperative deaths by haemorrhagic shock and
      peritonitis--mortality 4.4. DISCUSSIONS: Reconstruction by using the large-bowel
      was justified through anatomic argumentation (sufficient vascular supply),
      technic argumentation (easy anastomosis, tension free, short time of execution),
      functional argumentation (good compliance of large-bowel to the new function).
      CONCLUSION: Coloesophagoplasty is an efficient method on the condition of a
      strict planning: continent gastrostomy and evolvement of vascular arcades due to
      previous vascular "carving".

PMID- 15739670
TI  - [The use of LapSim virtual reality simulator in the evaluation of laparoscopic
      surgery skill. Preliminary results].
AB  - The aim of this study is to establish if the results obtained in the evaluation
      of the candidates for the laparoscopic surgery competence using the LapSim
      virtual reality simulator are comparable with intraoperative evaluation. For this
      study has been evaluated in front of the LapSim and in the operating room a
      number of 12 surgeons who have achieved the criteria for laparoscopic surgery
      competence evaluation. The results of any one of the candidates have been
      evaluated, on Lapsim and by the exam committee in the operation room relating to
      four criteria: (1) utilization of 300 camera; (2) manipulation and coordination
      of laparoscopic instruments, suturing; (3) grasping and cutting; (4) clip
      applying. The evaluation has been made relating to the time need for every
      candidate to perform the asked task, and the subjective evaluation of the
      examining committee with marks from 1 to 10. The LapSim evaluation, in
      concordance with intraoperative evaluation managed to establish 2 candidates with
      deficiency in manipulation and coordination of laparoscopic instruments, and
      difficulty in the laparoscopic bidimensional field orientation. We consider this
      experiment only the beginning in the evaluation of the utility of virtual reality
      simulator in the training and examination of the results in laparoscopic surgery.
      We consider that large series of subjects with different levels of knowledge in
      laparoscopic surgery have to be evaluated to conclude if the benefit of
      laparoscopic surgery virtual reality simulator is the same as in airplane pilots.

PMID- 15739671
TI  - [Laparoscopic mini gastric bypass for the treatment of morbid obesity. Initial
      experience].
AB  - The mini-invasive treatment of morbid obesity represents a priority of our
      surgical team. The majority of the patients have been operated on restrictive
      bariatric procedures. The technique we are presenting is indicated for the
      extreme and super obese patients (BMI >50 kg/m2) for whom the restrictive
      procedures are less efficient. In these situations we have performed a mixed
      procedure, combining two principles restriction and malabsorption by creating a
      low capacity gastric tube connected to the jejunum through a linear stapled
      anastomosis. The name of these procedure is mini gastric bypass and our
      experience is consisting of 7 patients, with BMI between 52.7 and 71.69 kg/m2,
      with very important comorbidities. In this paper we are describing the specifics
      of the laparoscopic approach and the postoperative results at 3-18 months. We
      have recorded one conversion to the open surgery, two hemorrhagic postoperative
      complications and one marginal ulcer (3 month post-operatively); all
      complications were treated conservatively. All the patients lost weight, the EWL
      at 12 months was between 45.26% and 77.65%, while the co-morbidities had a
      significant good evolution. The procedure was efficient, well accepted and
      tolerated by the patients.

PMID- 15739672
TI  - [Hepatic hydatid cyst ruptured in the peritoneum].
AB  - Romania is an endemic region for hydatid cyst and has a high incidence of hepatic
      hydatid cysts. If the intrabiliary rupture is the most frequent complication
      encountered, rupture in the peritoneum is rare, with exact data not available.
      Between 1993-2002 160 patients with hepatic hydatid cysts were operated. Six of
      them had an intraperitoneal ruptured cyst. Ultrasound raised the suspicion of
      hepatic hydatid cyst ruptured in the peritoneum in 4 cases, in one case the
      intact cyst migrated in the lower abdomen were it was mistaken for an ovarian
      cyst. After a thorough lavage with hypertonic serum, the parasite was evacuated,
      the pericyst partially removed and the cavity collapsed with non-absorbable
      sutures. The postoperative course was uneventful. Prophylaxis with benzimidazolic
      drugs started days 2-3 PO. At a follow-up between 1-4 years no peritoneal
      hydatidosis was detected. In the intraperitoneal ruptured hydatid cyst the
      hypertonic serum and benzimidazolic drugs can be useful in preventing peritoneal
      seedings.

PMID- 15739673
TI  - [Predictive value of diagnostic tests in polytrauma patients with abdominal and
      craniocerebral injuries].
AB  - In a study on 1024 polytrauma patients with craniocerebral injury, abdominal
      injury was present in 206 (20.11%) of them. In order to identify the
      intraabdominal organs injury, physical examination and specific diagnostic tests
      will be used. Their value was calculated by means of informational indices. The
      main indices, sensitivity, positive predictive value and accuracy were: for
      physical examination = 81.06%, 90.3%, 94.72%; for peritoneal lavage = 94.17%,
      95.12%, 97.94%; for abdominal computed tomography = 98.44%, 97.65% and 99.25%. As
      one might expect the abdominal computed tomography is the most accurate method
      for the diagnosis of intraabdominal organs injuries.

PMID- 15739674
TI  - [Minimally invasive approach of the cervical endocrine glands].
AB  - Improved preoperative functional and topographic diagnostic techniques and
      availability of intra-operative hormone monitoring, stimulated the introduction
      of video-assisted minimally invasive operations in parathyroid and thyroid
      surgical pathology. The first cases of such pathology operated on in our clinic
      are presented. The first one is a 62 year old man with renal hyperparathyroidism
      consecutive to a chronic renal insufficiency and hemodialysis from five and three
      years respectively. The technique of a minimally invasive gapless resection of
      all four "adenomised" parathyroid glands using laparoscopic and classic
      instruments is described. Fragments of one gland are implanted in the left
      forearm musculature. The second case was a 48 year old woman with a three cm
      diameter right toxic adenoma. With a lateral 15 mm incision, dissociation of the
      musculature and adequate moving of the retractors the excision of the thyroid
      nodule was done in 25'. The video-assisted minimally invasive approach allows
      magnification and adequate identification and removal of endocrine secreting
      tissues in thyroid and parathyroid pathology. The authors believe that these
      techniques represent a feasible and attractive alternative to conventional
      surgery.

PMID- 15739675
TI  - A difficult case of mediastinal parathyroid adenoma: theoretical and clinical
      considerations.
AB  - About one quarter of patients with primary hyperparathyroidism have ectopic
      parathyroid tissue. The majority of parathyroid glands can be reached through a
      cervical approach, but in about 2% of the cases the ectopic gland is in the
      mediastinum in a location that requires a thoracic approach. Failure to remove
      ectopic mediastinal parathyroid tissue results in persistent hyperparathyroidism.
      Reoperative exploration for persistent hyperparathyroidism is often difficult
      even in the hands of experienced surgeons. Recent advances in preoperative
      localization techniques and intraoperative parathyroid hormone measurement have
      improved the rates of successful resection. We present a difficult case of
      persistent hyperparathyroidism secondary to an ectopic middle mediastinal
      parathyroid adenoma, which was eventually successfully managed in a specialised
      unit.

PMID- 15739677
TI  - [Upper digestive haemorrhage of a rare cause: benign duodenal schwannoma].
AB  - The upper gastrointestinal bleeding is a common cause of admission to hospital.
      Neurogenic tumors of the duodenum are extremely rare and represent an unusual
      cause of gastrointestinal hemorrhage. The treatment is endoscopic or surgical
      total excision. In case of ulcerated large tumors situated periampullary
      pancreaticoduodenectomy (Whipple's or Traverso-Longmire's) represents an
      efficient solution. In addition, their high index of malignancy justifies this
      trend. We present a case of schwannoma of the second portion of the duodenum with
      several episodes of upper GI bleeding treated by Trasverso-Longmire
      pancreaticoduodenectomy.

PMID- 15739676
TI  - [Peritoneo-saphenous shunt for the treatment of ascites].
AB  - The life quality of the patient suffering from hepatic cirrhosis is affected by
      ascites refractory to drugs treatment. In the last 30 years, in the ascites
      treatment there were performed peritoneo-jugular shunts through synthetic
      prosthesis with unidirectional valve-LeVeen, Denver. The siliconated prostheses
      are expensive and in the process of time complications are registered consisting
      of clogged valve or obstruction, requiring thus their replacement. The
      unidirectional drainage of the ascites can also be performed through peritoneo
      saphenous shunt. In our clinic, the peritoneo-saphenous shunt was applied for the
      first time in 2004, in three patients with hepatic cirrhosis with ascites
      refractory to drugs treatment. The postsurgical evolution was favourable, a
      gradual increase of diuresis and reduction of abdominal diameter being registered
      in all the three cases. CONCLUSIONS: the peritoneo-saphenous shunt is a simple
      procedure, it does not require special devices and it can be applied with success
      in the treatment of refractory ascites.

PMID- 15739678
TI  - [Deep liver wound treated by internal compression with Blakemore catheter].
AB  - High incidence of polytraumas of different etiology determines special problems
      of treatment, the emergency surgeon frequently facing serious and complex
      injuries the most frequently in unstable patients and therefore difficult to be
      treated. This paper presents the case of a 19 years old patient, victim of a
      heteroaggression; clinical examination reveals an unique abdominal wound,
      surgical procedure showed a liver lesion with massive hemoperitoneum. Authors
      expose a series of emergency procedures principles for unstable patients and also
      an unusual method in the treatment of a liver wound. Actually, this method means
      catheterization of the liver wound with a Blakemore catheter. The esophageal
      balloon is full fill to make a positive pressure on this wound. Good evolution of
      the case justifies this method to be used as an alternative procedure to other
      haemostatic methods (liver resections, hepatic artery ligature etc.).

PMID- 15739679
TI  - Pediatric nursing.

PMID- 15739681
TI  - Do you have the "write" stuff? Being a nurse journalist.

PMID- 15739680
TI  - New grad? Be prepared to look great.

PMID- 15739683
TI  - Tips on taking the NCLEX-RN.

PMID- 15739682
TI  - Your bright future in geriatric nursing.

PMID- 15739684
TI  - Questions & answers about your nursing license and mobility.

PMID- 15739685
TI  - Your career as a nurse educator.

PMID- 15739686
TI  - Professionalism--duties and privileges.

PMID- 15739687
TI  - A target glitter study.
AB  - A target study was conducted using four different pre-selected types of
      commercial glitter particles. Recipient areas in the general environment around
      San Diego, California were tested. Glitter particles were recovered using double
      sided tape affixed to square plastic Petri dishes. White light microscopy was the
      only search/identification method used. Additionally, a test was performed of the
      transferability of cosmetic glitter. Glitter particles were found to readily
      transfer. Of a total of 48 tape lifts from the general environment, 23 were found
      to contain at least one glitter particle. But due to the wide variety of glitter
      particles in terms of colour, shape, size, and surface morphology, the likelihood
      of transfer of one or more specific target particles was small.

PMID- 15739688
TI  - The individuality of fibres used to provide forensic evidence--not all blue
      polyesters are the same.
AB  - Fibres used in forensic casework suffer from a disadvantage common to other forms
      of trace evidence--it is not possible to state with absolute certainty that they
      originate from a specific source. Target fibre studies, population studies and
      research on 'blocks of colour' have effectively demonstrated the polymorphism of
      textile fibres (particularly man-made ones) and have shown that when a fibre is
      believed to have a specific putative source, the chance that it has originated
      from a different source purely by coincidence is extremely remote. A study by
      Houck MM (Houck MM, Inter-comparison of unrelated fibre evidence. Forensic
      Science International 2003; 135: 146-149) has shown that no coincidental matching
      fibres were recovered from items of clothing examined in 20 unrelated crimes. The
      study involved over two million comparisons. This work goes a step further, and
      using the example of blue polyester fibres shows that even within a very narrow
      segment of the whole general fibre population, many examples of a specific
      colour/type of man-made fibre taken from random sources can be compared and the
      chance of any two being the same is very low. These studies should help to show
      the specificity and value of transferred fibres in providing forensic evidence.

PMID- 15739689
TI  - A brush fire forensic case.
AB  - In Italy, every summer forest fires attract public attention due to the number of
      victims, the intensity of the fires, the areas devastated, the environmental
      damage and the loss of property. Excluding some fires by natural causes, other
      causes are related to the social, economic, and productive profile of the
      territory. The erroneous expectation is that wooded areas destroyed by fire can
      then be used for private interests. Often, a fire, started to clear a small area,
      can completely change the expected result, producing disaster, loss of property,
      destruction of entire forests and resident fauna, and kill innocent people. In
      this case report, the reconstruction of an arson scene, the analytical techniques
      and the results obtained are illustrated in this paper, with the aim of sharing
      with other research laboratories the current knowledge on forest fire.

PMID- 15739690
TI  - A simple logical approach to questioned envelopes examination.
AB  - This case report outlines research undertaken as the result of a document
      examination case in which two envelopes were involved. The combination of the
      circumstances of the case and the results of the examination allows a simple
      application of a logical approach to pre-assess the probability that an envelope
      (or a package) potentially recovered at a suspect's home comes from the same
      batch (same source) as questioned envelopes. This highlights that it is useful to
      examine envelopes.

PMID- 15739691
TI  - Founders' Lecture.

PMID- 15739693
TI  - Students' destinations.

PMID- 15739692
TI  - Learning from experience: developments in forensic investigation from case
      histories.

PMID- 15739694
TI  - Assessment for improvement: healthcare commission consults on new approach.

PMID- 15739695
TI  - The role of deliberate hypotension.

PMID- 15739696
TI  - Give oxygen, get a blood pressure... but don't overdo it.

PMID- 15739697
TI  - Oxygen: could there be too much of a good thing?

PMID- 15739698
TI  - Hot or cold? In support of cold.

PMID- 15739699
TI  - Hot or cold? Warm heart, cool brain.

PMID- 15739700
TI  - Damage control for torso trauma.

PMID- 15739701
TI  - Damage control in orthopaedic injuries.

PMID- 15739702
TI  - Endotracheal intubation in the field: pro position.

PMID- 15739703
TI  - Endotracheal intubation in the field: con position.

PMID- 15739704
TI  - Uncross-matched red blood cells save lives.

PMID- 15739705
TI  - Uncross-matched blood is unnecessary.

PMID- 15739706
TI  - Thinking about the SHO curriculum.
AB  - This discussion of the reform of senior house officer (SHO) training draws on
      important evidence from the evaluation of a pilot curriculum for basic surgical
      education. Variations and anomalies in SHO teaching and learning were detected,
      many related to the service context. They highlight the need for explicit
      curriculum frameworks that build on, and are consonant with, current best
      practice in SHO education.

PMID- 15739707
TI  - Treatment for heart failure: good news and bad.
AB  - Heart failure is a common disorder associated with significant morbidity,
      mortality and financial burden to health services. The pharmacotherapy of heart
      failure, including new treatments, will be discussed.

PMID- 15739708
TI  - Non-alcoholic fatty liver disease.
AB  - This article reviews the nomenclature, clinical and histological basis for a
      diagnosis of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis,
      its natural history, pathophysiology and an approach to clinical management.

PMID- 15739709
TI  - Bite wounds of genitalia: clinical presentation and management.

PMID- 15739710
TI  - Renal medullary carcinoma: beware of diagnosing a urinary tract infection in a
      young sickle cell patient.

PMID- 15739711
TI  - Renal failure in an infant.

PMID- 15739712
TI  - A case of ocular myasthenia gravis and Miller-Fisher syndrome.

PMID- 15739713
TI  - The opening of Guy's Hospital.

PMID- 15739714
TI  - Activated protein C in a pregnant patient with severe sepsis.

PMID- 15739715
TI  - Unusual foreign body in the soft palate.

PMID- 15739716
TI  - On the value of being a journal reviewer.

PMID- 15739717
TI  - Advances in autism research.

PMID- 15739718
TI  - Comparison of clinical and videofluoroscopic evaluation of children with feeding
      and swallowing difficulties.
AB  - The objectives of this study were threefold: (1) to evaluate the accuracy of
      clinical evaluation compared with videofluoroscopic swallowing studies (VFSSs) in
      the detection of penetration and aspiration in children of age 0 to 15 years
      presenting with feeding and swallowing problems; (2) to assess the relationship
      between therapists' confidence ratings in making judgements about the presence or
      absence of penetration and aspiration, and the accuracy of their evaluation as
      confirmed by VFSSs; (3) to identify clinical predictors of penetration and
      aspiration during clinical evaluation of children with feeding and swallowing
      difficulties. We used a prospective study to evaluate the sensitivity,
      specificity, and positive and negative predictive values of a diagnostic clinical
      evaluation compared with VFSSs (criterion standard). Clinical evaluation and
      videofluoroscopy forms for oral motor and swallowing evaluation, which included
      potential indicators of aspiration, were designed for this project. Seventy-five
      children with feeding problems participated (33 females, 42 males; age range 0 to
      14 years, mean 2 years; 62% of participants younger than 12 months). For fluids,
      clinical evaluation showed a sensitivity of 92% for aspiration. For solids,
      sensitivity for detecting aspiration was 33%. Analysis of the therapists' mean
      confidence ratings compared with the accuracy of their judgement demonstrated
      that when therapists were very sure that the child was aspirating or penetrating
      or not, they were correct. When the therapists were unsure, then the accuracy of
      prediction was not as good. Cough was the most significant predictor (p < 0.05)
      of fluid aspiration and penetration. We conclude that clinical evaluation with
      experienced clinicians can detect aspiration and penetration of fluids in
      children of varied ages and diagnoses, but that it is not accurate with solids.

PMID- 15739719
TI  - Effect of an oral stimulation program on sucking skill maturation of preterm
      infants.
AB  - This study assessed the effect of an oral stimulation program on the maturation
      of sucking skills of preterm infants. Thirty-two preterm infants (13 males, 19
      females), appropriate size for gestational age (gestational age at birth 28 wks,
      SD 1.2wks; birthweight 1002g, SD 251g), were randomly placed into experimental
      and control groups. The experimental group received a daily 15-minute oral
      stimulation program, consisting of stroking the peri- and intra-oral structures,
      for 10 days before the start of oral feedings. Sucking measures were monitored
      with a specially-designed nipple-bottle apparatus. Results indicate that the
      experimental group achieved full oral feedings 7 days sooner than the control
      group, and demonstrated greater overall intake (%), rate of milk transfer
      (mL/min), and amplitude of the expression component of sucking (mmHg). There was
      no difference in sucking stage maturation, sucking frequency, and amplitude of
      the suction component of sucking. Endurance, defined as ability to sustain the
      same sucking stage, sucking burst duration, and suction and expression amplitudes
      throughout a feeding session, was not significantly different between the two
      groups. The stimulation program enhanced the expression component of sucking,
      resulting in better oral feeding performance.

PMID- 15739720
TI  - Handwriting performance in preterm children compared with term peers at age 6 to
      7 years.
AB  - Preterm infants are at high risk for developmental impairments at school age.
      However, the impact of these impairments on important life skills, such as
      handwriting, is unknown. Forty-eight first-grade children (27 males, 21 females;
      mean age 6y 7mo, SD 3.9mo; range 6y 1mo to 7y 3mo) born preterm (birthweight <
      1250g; gestational age < 34wks), without major physical or cognitive
      disabilities, were matched to 69 healthy, term control children (32 males, 37
      females; mean age 6y 10mo, SD 3.6mo; range 6y 3mo to 7y 4mo) by sex and school
      class. All children were assessed using the Evaluation Tool of Children's
      Handwriting-Manuscript and several sensorimotor measures. Preterm children
      demonstrated significantly lower legibility and slower speed scores (p < 0.01)
      compared with control children for most of the handwriting tasks. Factors
      associated with legibility were visual perception and eye-hand coordination (r <
      0.50; p < 0.05) and sex (r < 0.12; p = 0.01). In-hand manipulation and finger
      identification (r < 0.43; p < 0.01) were significantly correlated with slow
      handwriting speeds. Behaviour difficulties associated with hyperactivity and poor
      attention (Connors Abbreviated Symptoms Questionnaire) had a confounding
      influence on both legibility and speed. These findings may help guide early
      identification efforts and medical/therapeutic interventions for preterm
      children.

PMID- 15739721
TI  - Mortality and causes of death in persons with Down syndrome in California.
AB  - This study investigated mortality and causes of death between 1988 and 1999 in
      14781 persons (6702 female) with Down syndrome in California, comparing age, sex,
      ethnicity, and other factors. Mean age at the start of follow-up was 14 years 8
      months (SD 14y 10mo). During the study period 600 persons died. The standardized
      mortality ratio (SMR) for the population was 5.5. Blacks were at greater risk
      than whites, Hispanics, or Asians (relative risk = 1.5). Mortality declined
      during the period, especially for children with congenital heart defects.
      Leukemia (SMR = 17), respiratory illnesses (SMR = 27), congenital anomalies (SMR
      = 72), and circulatory diseases (SMR = 5.3) accounted for most of the excess
      mortality. With the exception of leukemia, cancer mortality was not different
      from that of the general population.

PMID- 15739722
TI  - Disabilities and cognition in children and adolescents with 22q11 deletion
      syndrome.
AB  - The purpose of this study was to investigate cognitive and other disabilities in
      children and adolescents with 22q11 deletion syndrome. Thirty-three children (15
      females, 18 males; age range 3 to 19y, median 7y 6mo) with 22q11 deletion were
      investigated for growth, development, neurology, cognition, motor function, and
      participation (measured as handicap**). Half of the children had never crawled,
      although they had shuffled, and commencement of walking was delayed (mean 18mo,
      SD 6mo). Hypotonia was found in 25 and poor balance in 24 of the 33 children; 17
      out of 27 had definite motor problems, including two with spastic hemiplegia.
      Intelligence quotient (IQ) range was 50 to 100. Eleven patients had an IQ below
      70, and 15 between 70 and 84. Verbal IQ was higher than Performance IQ. Level of
      handicap within the study group was considered moderate, and all but one child
      had extra support at school. We conclude that children with 22q11 deletion
      syndrome have multiple neurological, motor, and cognitive problems. Although the
      severity and number of problems varies, the combination of impairments and
      disabilities results in a low level of participation.

PMID- 15739723
TI  - Mitochondrial dysfunction in autism spectrum disorders: a population-based study.
AB  - A minority of cases of autism has been associated with several different organic
      conditions, including bioenergetic metabolism deficiency. In a population-based
      study, we screened associated medical conditions in a group of 120 children with
      autism (current age range 11y 5mo to 14y 4mo, mean age 12y 11mo [SD 9.6mo],
      male:female ratio 2.9:1). Children were diagnosed using Diagnostic and
      Statistical Manual of Mental Disorders criteria, the Autism Diagnostic Interview-
      Revised, and the Childhood Autism Rating Scale; 76% were diagnosed with typical
      autism and 24% with atypical autism. Cognitive functional level was assessed with
      the Griffiths scale and the Wechsler Intelligence Scale for Children and was in
      the normal range in 17%. Epilepsy was present in 19 patients. Plasma lactate
      levels were measured in 69 patients, and in 14 we found hyperlactacidemia. Five
      of 11 patients studied were classified with definite mitochondrial respiratory
      chain disorder, suggesting that this might be one of the most common disorders
      associated with autism (5 of 69; 7.2%) and warranting further investigation.

PMID- 15739724
TI  - Is the presence of urinary indolyl-3-acryloylglycine associated with autism
      spectrum disorder?
AB  - To test whether the presence of indolyl-3-acryloylglycine (IAG) is associated
      with autism, we analyzed urine from population-based, blinded cohorts. All
      children in York, UK with autism spectrum disorders (ASDs), diagnosed using ICD
      10 research diagnostic criteria, were invited to participate. Fifty-six children
      on the autism spectrum (mean age 9y 8mo, SD 3y 8mo; 79% male) agreed to
      participate, as did 155 children without ASDs (mean age 10y, SD 3y 2mo; 54% male)
      in mainstream and special schools (56 of whom were age-, sex-, and school-matched
      to children with ASDs). IAG was found at similar levels in the urine of all
      children, whether IAG concentrations or IAG:creatinine ratios were compared.
      There was no significant difference between the ASD and the comparison group, and
      no difference between children at mainstream schools and those at special
      schools. There is no association between presence of IAG in urine and autism;
      therefore, it is unlikely to be of help either diagnostically or as a basis for
      recommending therapeutic intervention with dietary manipulation. The significance
      of the presence of IAG in urine has yet to be determined.

PMID- 15739725
TI  - Ataxia, autism, and the cerebellum: a clinical study of 32 individuals with
      congenital ataxia.
AB  - The suggested link between autism and cerebellar dysfunction formed the
      background for a Swedish clinical study in 2001. Thirty-two children (17 females,
      15 males; mean age 12y, SD 3y 10mo; range 6 to 21y) with a clinical suspicion of
      non-progressive congenital ataxia were examined, and parents were interviewed
      about the presence of neuropsychiatric problems in the child. Twelve children had
      simple ataxia, eight had ataxic diplegia, and 12 had 'borderline' ataxia. All but
      one of the 32 children had a mild to moderate gross motor disability according to
      Gross Motor Function Classification System (15 were categorized as level I, 16 as
      level II, and one child as level IV). Neuroimaging and neuropsychological testing
      were achieved in most cases. There was a strong association between learning
      disability* and autism spectrum disorder (often combined with hyperactivity
      disorder) on the one hand, and both simple and borderline 'ataxia' on the other,
      but a weaker link between ataxic diplegia and neuropsychiatric disorders. A
      correlation between cerebellar macropathology on neuroimaging and
      neuropsychiatric disorders was not supported. Congenital ataxia might not be a
      clear-cut syndrome of cerebellar disease, but one of many signs of prenatal
      events or syndromes, leading to a complex neurodevelopmental disorder including
      autism and learning disability.

PMID- 15739726
TI  - DOPA-sensitive dystonia-plus syndrome.
AB  - We report on two sisters with a childhood-onset form of predominantly axial
      dystonia with marked diurnal fluctuations. Onset of clinical features was at
      approximately 6 years of age. Associated features included marked fatigue, slight
      facial dysmorphism, short stature, obesity, and learning disability*. Dystonia
      and fatigue responded to 3,4-dihydroxyphenylalanine (DOPA) therapy, with
      recurrence of symptoms upon withdrawal; the efficacy has been maintained over 7
      years. Other symptoms were not influenced. There was no other case in the family
      (which included an older, healthy brother), except for non-specific fatigue
      without dystonia in the mother, and there was no significant family history
      except for obesity on the father's side. These observations are discussed in
      relation to the classical descriptions of Segawa syndrome, and to more recent
      reports of childhood onset, age-related, and transient benign paroxysmal tonic
      upgaze and ataxia. The combination of symptoms, their sensitivity to DOPA, and
      their persistence throughout childhood constitute, to our knowledge, a new
      clinical entity, which we propose to categorize as a DOPA-sensitive dystonia-plus
      syndrome.

PMID- 15739727
TI  - Epilepsy and evidence-based medicine: a vote of confidence in expert opinion from
      the National Institute for Clinical Excellence?

PMID- 15739728
TI  - Acyl-CoA dehydrogenase deficiency: varieties with neurological involvement.

PMID- 15739729
TI  - AACPDM meeting--Los Angeles, September 2004.

PMID- 15739730
TI  - Audit of the use of chloral hydrate as an acute treatment for childhood
      seizures'.

PMID- 15739731
TI  - 'Ictus emeticus in a prolonged frontotemporal seizure secondary to a brain
      tumour'.

PMID- 15739732
TI  - Occupational standards for maternity care.

PMID- 15739733
TI  - Putting pregnancy in the picture.

PMID- 15739734
TI  - Cultivating tall poppies.

PMID- 15739735
TI  - Building successful teams: sparkling fountains of innovation.

PMID- 15739736
TI  - Maternity support workers: what is their role?

PMID- 15739737
TI  - Students and the booking visit.

PMID- 15739738
TI  - Normal birth--is it possible in the 21st century?

PMID- 15739739
TI  - Guide to current awareness services.

PMID- 15739740
TI  - With woman, with midwife.

PMID- 15739741
TI  - Re: Does anyone care?

PMID- 15739742
TI  - Re: Does anyone care?

PMID- 15739744
TI  - Wearing purple.

PMID- 15739743
TI  - Response from Jon Skewes, RCM Director of Employment Relations and Development.

PMID- 15739745
TI  - Doing our part.

PMID- 15739746
TI  - That 'document' word.

PMID- 15739747
TI  - Prenatal exposure to illegal drugs.

PMID- 15739748
TI  - Help is available.

PMID- 15739749
TI  - Joe Nelson, MD.

PMID- 15739750
TI  - Update: emerging evidence leads to new guidelines.

PMID- 15739751
TI  - Screening internal auditory canals.

PMID- 15739752
TI  - Opioid-induced pain.

PMID- 15739753
TI  - Violence education: dissolving the denial.

PMID- 15739754
TI  - Summer Genetics Institute.

PMID- 15739755
TI  - School connectedness, anger behaviors, and relationships of violent and
      nonviolent American youth.
AB  - PROBLEM: Youth violence research often focuses on risk factors arising from early
      familial interactions rather than school-related factors. METHODS: Via an
      Internet questionnaire, 282 girls and boys (ages 7-19, mean 15.3) from 47 states
      and Washington, DC, reported on school connectedness, interpersonal
      relationships, and anger behaviors. FINDINGS: Substantial percentages of violent
      youth did not perceive themselves to be liked by classmates and reported
      loneliness. If not liked by classmates, 80% hated school. Likers and haters of
      school differed on seven variables (all p < or = .01). CONCLUSIONS: Insufficient
      attention is paid to the alienation experienced by disliked and lonely students.
      Mental health nurses could play a pivotal role in fostering change in the social
      climate of schools and helping youth to achieve better anger management and
      social skills.

PMID- 15739757
TI  - Violent lives of women: critical points for intervention--phase I focus groups.
AB  - PROBLEM: To identify critical developmental periods, experiences, and events in
      women's lives associated with violence to guide a larger study. METHODS: Two
      focus groups of 10 women each (N = 20) were conducted to determine the critical
      times when girls and women might be exposed to violence. FINDINGS: Broad themes
      in the data were developmental periods, abusers, staying in the relationship,
      leaving the relationship, parenting, and living with violence. The women in these
      focus groups clearly identified times of increased risk for violence in their
      lives: establishing intimate relationships, pregnancy, childrearing years, and
      times when substance abuse is occurring. CONCLUSIONS: While clinicians should be
      vigilant for the presence of domestic violence with all clients, it is important
      to know when a woman experiences increased risk for violence. The findings
      indicate a need for education for communities, those who provide care for women
      and children, and people in whom victims may confide.

PMID- 15739756
TI  - Life after death: grief therapy after the sudden traumatic death of a family
      member.
AB  - TOPIC: Survivors of the sudden traumatic death of a family member are at
      increased risk for complicated grief and bereavement. PURPOSES: To present the
      complicating factors inherent to sudden traumatic death in order to promote
      adaptive grieving in the survivors. SOURCES: A comprehensive review of the
      existing bereavement literature, clinical anecdotes, and therapeutic experiences.
      CONCLUSIONS: Grief is a process and not an endpoint. The goal of grief is not to
      forget about the loss, a commonly stated goal of survivors; rather, the goal is
      to remember the decedent, understand the changes created by the loss, and
      determine how to reinvest in life.

PMID- 15739758
TI  - Poststroke depression: psychopharmacological considerations.
AB  - PSD is a common psychiatric complication of stroke. It is often underrecognized
      and untreated. Numerous studies show that untreated PSD impedes the
      rehabilitation and recovery process, jeopardizes quality of life, and increases
      mortality. Successful management of the PSD requires early recognition and
      initiation of appropriate treatment to facilitate an optimal level of
      functioning. As active members of the interdisciplinary treatment team,
      psychiatric consultative-liaison nurses play a pivotal role in facilitating
      positive treatment outcomes during both the acute and rehabilitation phases in
      the management of PSD.

PMID- 15739759
TI  - Preserving blind peer review of electronic manuscript files.
AB  - Peer review of manuscripts for potential publication has become an intrinsic
      component of the scientific process, and is aimed at improving the manuscript's
      quality through unbiased, independent, and critical assessment by experts who are
      not on the journal's staff (International Committee of Medical Journal Editors,
      2003).

PMID- 15739760
TI  - The insider's view.

PMID- 15739761
TI  - Moving up the career ladder: staff nurses writing for publication.
AB  - Facilitating the knowledge and abilities of staff nurses interested in climbing
      an organization's career ladder helps the nurse, the profession, and patients.
      Strategies to overcome obstacles and promote collaboration in writing for
      publication are addressed.

PMID- 15739762
TI  - [Cancerous antigen CA-125: its biology and diagnostic value (literature review)].

PMID- 15739763
TI  - [Research of aggregation of erythrocytes by laser diffractometry].

PMID- 15739764
TI  - [The activity of superoxide dismutase and glutathione peroxidase and the level of
      malonic dialdehyde in prematures with hypoxic disorders of the central nervous
      system].
AB  - The activity of superoxide dismutase and glutathione peroxidase and the level of
      malonic dialdehyde were studied 53 prematures with hypoxia of the central nervous
      system. A low activity of superoxide dismutase and glutathione peroxidase, which
      depended on a prematurity degree and on a content of malonic dialdehyde in the
      erythrocyte cell membranes, was found. A higher level of malonic dialdehyde in
      erythrocyte membranes was shown to be an unfavorable prognostication factor for
      the development of intraventricular hemorrhages in prematures.

PMID- 15739765
TI  - [Analysis of anions in biological fluids by capillary electrophoresis].

PMID- 15739766
TI  - [Laboratory syndromes in non-specific reactive lesions of the liver in patients
      with acute destructive cholecystitis].

PMID- 15739767
TI  - [Lipid peroxidation and tumor dimensions in stomach cancer].
AB  - The parameters of lipid peroxidation were examined in blood serum of 40 patients
      with stomach cancer by induced chemiluminescence (CL)--Republican Research Center
      of Oncology, Healthcare Ministry of Uzbekistan. The CL parameters were
      demonstrated to increase alongside with the growing tumor mass. The induced CL of
      blood serum characterizes the status of lipid peroxidation and is a direct
      reflection of the body's reaction to tumor growth. The method of induced CL can
      be used on in clinical practice as an additional diagnostic test describing the
      tumor growth course in stomach cancer.

PMID- 15739768
TI  - [Antithrombotic therapy and its laboratory monitoring (lecture)].

PMID- 15739769
TI  - [The oxidative stress in platelets of patients with ovary cancer as observed at
      chemotherapy].
AB  - Disorders in the main chains of platelet antioxidant protection were examined in
      32 patients with primarily-diagnosed ovary cancer who were postoperatively
      receiving chemotherapy according to PC. The activity of antioxidant-protection
      enzymes (superoxide dismutase, catalase, glutation-S-transferase) as well as the
      content of malonic dialdehyde (MDA) and glutathione were examined after each
      course of chemotherapy. The data obtained were compared with the aggregation
      ability of platelets, with the content of fibrinogen and with the count of
      platelets. The parameters of the antioxidant system in platelets were examined
      for control in 30 virtually healthy women. The results denote that the oxidant
      stress progression in the body due to the growing tumor and aggravating because
      of chemodrugs deregulates the free-radical processes in platelets, which can
      affect their functional properties or rheological blood properties.

PMID- 15739770
TI  - [Analysis of studies of reticulocytes and of some other indices of the erythron
      system in patients with type 2 diabetes mellitus].

PMID- 15739771
TI  - [An examination method for chemiluminescence of whole-blood leucocytes].
AB  - The chemiluminescence examination methods have been limited in use due to a lack
      of standard techniques for the preparation and storage of biological samples. The
      methods of sampling the blood and the conditions of its storage and
      transportation as well as other factors essentially affect the functional state
      of cells through activating them. The suggested technique keeps the values of
      blood chemiluminescence stable for 2 hours in measurements of spontaneous
      chemiluminescence and for 6 hours in measurements of stimulated
      chemiluminescence. For the purpose, whole blood is mixed, in test-tubes, with a
      0.27% solution of disodium EDTA. It is stored in refrigerator at 0 to 5 degrees
      C. Blood is diluted by Henk solution and luminol for measurements.

PMID- 15739772
TI  - [Cell-cooperation integrated test for the detection of immune reactivity to Shiga
      toxin in patients with acute intestine infection].
AB  - Described are the results of approbation of the cell-migration screening test
      reflecting the outcome of cooperation between T- and B-cells and macrophages. It
      was shown, in adults and children with intestine infection, to be a highly
      effective tool for the detection of suppressed immune response during early
      disease stages at stimulation in vitro by Shiga toxin at nano- and picogram
      concentration; it can also be used for the evaluation of the shaping specific
      anti-Shiga-toxic immune response. The parameters of the migration activity of
      peripheral-blood leucocytes at exacerbation and convalescence were demonstrated
      to correlate with the age of sick children and with the severity of intestine
      infection as well as with the level of a Shiga-like toxin detected in
      coprofilters and circulating immune complexes.

PMID- 15739773
TI  - [ELISA-based determination of natural antibodies to endothelial NO-synthase in
      human blood and tear].
AB  - Research of natural antibodies (NAA) is a new trend in immunohistochemistry. NAA
      shape up, in biological fluids, as normal human endogenous low- and high-weight
      substances, e.g. angiotensin 2, bradykinin and others, and play the regulatory
      role in homeostasis. Endothelial NO-synthase (e-NOS) is a key enzyme in the path
      of NO shaping. An e-NOS alteration is important in the pathogenesis of diabetic
      microangiopathy including retinopathy. We determined, within our case study, the
      level of NAA to e-NOS in blood and tears of patients with diabetic retinopathy
      and in donors. The level of NAA to e-NOS was found to be twice higher in tears
      versus blood in all groups of patients. It depended on specific features and
      complications of diabetes mellitus.

PMID- 15739774
TI  - [ Information value of biochemical tests in district clinics].

PMID- 15739775
TI  - Religious individuals: evaluating their intrinsic and extrinsic motivations at
      the implicit level of awareness.
AB  - Explicit cognitions are those that occur with intention and conscious awareness;
      implicit cognitions occur without such intention and awareness. Whereas some
      investigations have demonstrated consistencies between beliefs maintained at
      these two levels of awareness, others have demonstrated inconsistencies. In the
      present research, participants performed a speeded-response task, a variation of
      the Implicit Association Test (A. G. Greenwald, D. E. McGhee, & J. L. K.
      Schwartz, 1998), to evaluate their implicit identification with intrinsic and
      extrinsic religious motivations. Also, participants completed a self-report
      measure to evaluate their corresponding tendencies toward explicit motivations.
      The results provided evidence for consistency between participants' implicit
      identification and their explicit identification with intrinsic and extrinsic
      religious motivations. The finding of this consistency has implications for the
      relationship between intrinsic religiousness and social-desirability effects.

PMID- 15739776
TI  - Satisfaction of Jewish and Arab teachers in Israel.
AB  - The author investigated the differences between Jewish Israeli and Arab Israeli
      teachers in their satisfaction with their work. Initially, the goal of the
      present study was to investigate whether there were demographic attributes (such
      as age, gender, and education) that differentiated between the two groups of
      teachers. Later, the author added two variables, teachers' perceptions of their
      occupation and teachers' perceptions of their principals' leadership styles, to
      the analysis to examine their contribution to the level of satisfaction for each
      group. Regression analyses revealed the significant power of the two added
      variables in predicting teacher satisfaction among both Jewish and Arab Israeli
      teachers. The author discussed implications of the findings in relation to
      principals' roles and teachers' perceptions.

PMID- 15739777
TI  - Belief in a just world and social perception: evidence for automatic activation.
AB  - The authors tested the hypothesis that beliefs in a just world are automatically
      activated and used in social perception. Under the guise of a perceptual
      vigilance task, the authors exposed 34 undergraduate women preconsciously to
      words that were either rape-related or neutral. Immediately after the exposure,
      participants read a date scenario that was ambiguous with respect to the man's
      aggressiveness and the extent to which the woman was responsible for the man's
      behavior. Afterwards, all participants evaluated the target man and woman on an
      impression task. The primary finding was that participants holding stronger
      beliefs in a just world perceived the target woman more negatively after
      experiencing the rape-related prime words than after experiencing the neutral
      words. This pattern is consistent with a research literature that shows that
      believers in a just world will often "blame the victim" in cases of rape. The
      present findings are important because they provide evidence that general,
      orienting beliefs are automatically activated in a manner similar to that shown
      by stereotype beliefs. The authors discussed implications for social perception.

PMID- 15739778
TI  - Interracial interactions at racially diverse university campuses.
AB  - The present research was an observational study of casual interracial and
      intraracial public-group interactions among African American, Asian American,
      Latino, and White students at 6 southern California State University campuses.
      Results indicated (a) that at these racially diverse public-university campuses,
      there was no difference between the percentages of interracial and intraracial
      groups; (b) specifically, that at the campus with the second largest percentage
      of non-White students, there were more interracial than intraracial interactions;
      and (c) that for each of the 4 ethnic groups, at the campuses with the largest
      percentages of the specific group, interactions were more likely to be
      intraracial than they were at campuses that had smaller percentages of the
      specific group. Despite reports of self-segregation, these findings suggest that
      when Whites are not the majority of students, interracial interactions are
      common.

PMID- 15739779
TI  - The components of sexual orientation, religiosity, and heterosexuals' impressions
      of gay men and lesbians.
AB  - In 2 studies, the authors explored whether emphasizing the sexual behavior of gay
      men and lesbians influences heterosexuals' impressions of gay male and lesbian
      targets. In both studies, participants read short vignettes of heterosexual and
      gay male or lesbian targets that described their sexual histories using
      information restricted to only 1 component of sexual orientation (emotion,
      behaviors, or fantasies). The results of Study 1 showed that participants rated a
      behavioral gay male target more negatively than they did the emotions and fantasy
      targets, and this difference was a function of participant religiosity. In Study
      2, participants rated the behavioral lesbian target more negatively than they did
      the emotions and fantasy targets; however, these differential ratings of the
      lesbian targets were not affected by participant religiosity.

PMID- 15739780
TI  - Gender subgroups and intergroup perception: adolescents' views of own-gender and
      other-gender groups.
AB  - The authors examined intergroup bias and perceived group variability regarding
      gender subgroups relevant to the adolescent culture. Participants were 126 high
      school students, between 16 years and 19 years of age, who listed male and female
      subgroups, performed a series of group perception tasks, and, for each subgroup,
      indicated whether they themselves belonged to the group. Results showed that
      adolescents' perceptions of gender subgroups were subject to in-group favoritism
      and out-group derogation, as well as to group homogeneity effects. In line with
      predictions derived from Optimal Distinctiveness Theory, male and female
      participants favored in-groups over own-gender and other-gender out-groups and
      favored other-gender out-groups over own-gender outgroups. Ambivalence was
      particularly high with other-gender out-groups. The authors discussed
      implications for future research on the development of gender prejudice and for
      interventions to reduce prejudice.

PMID- 15739781
TI  - Mechanisms of regulation of sexual behavior.

PMID- 15739782
TI  - Quantitative characterization of the cellular elements of human cerebellar nuclei
      at different ages.
AB  - A quantitative assessment of the cellular elements present in the nuclei of the
      human cerebellum was performed using subjects aged 22-90 years. A series of
      horizontal sections of cerebellar nuclei was studied. stained with hematoxylin
      and eosin. The numbers of neurons and gliocytes per unit area were measured on
      sections, with subsequent calculation of their ratios (the glial index). These
      experiments showed that aging is associated with decreases in the content of
      neurons and increases in the content of gliocytes. The extent of these changes
      increases as ontogenesis proceeds.

PMID- 15739783
TI  - Organotypic cultures of free-floating slices of human embryo medulla oblongata.
AB  - The aim of the present work was to produce organotypic cultures of human embryo
      brain tissues, as needed for investigation of the effects of serum factors on
      mental diseases and their pharmacological treatment. Cultures were made using
      slices of medulla oblongata from human embryos aged 9-10 weeks, obtained from
      medical abortions. Free-floating slices were cultured using a modified roller
      method for four weeks. Light and electron microscopy, along with
      immunocytochemistry, demonstrated that cultured slices showed differentiation and
      growth of neurons, astro- and microgliocytes, with formation of the synaptic
      contacts and glioneuronal interactions typical of organotypic cultures. However,
      along with differentiated neurons and glial cells, there was some persistence of
      undifferentiated cellular elements with signs of stem cells and neuron and
      gliocyte precursor cells. These experiments showed that organotypic roller
      cultivation of free-floating slices of human embryo brain tissue can be used to
      study the processes of neuron and gliocyte development, the mechanisms of
      neurotoxicity and neuroprotection using a variety of morphological (including
      stereological) and biochemical study methods.

PMID- 15739784
TI  - Post-traumatic survival of sensory neurons of different subpopulations.
AB  - Immunohistochemical studies were performed to address the expression of the high
      molecular-weight component of the neurofilament triplet NF200 (a marker of
      neurons forming A fibers) and the binding of isolectin B4 (IB4) by neurons of the
      L4-5 spinal ganglia after ligation or section of the sciatic nerve in rats. A
      total of 15% of neurons in the ganglia of intact rats expressed NF200. By 90 days
      after nerve ligation, the proportion of NF200+ neurons decreased two-fold;
      administration to these rats of the nerve regeneration stimulator xymedone
      increased the number of NF200+ neurons by 50.7% compared with controls (ligation,
      no treatment). In intact rats, 23.6% of neurons bound IB4. The proportion
      decreased by 2.6% 30 days after nerve ligation and to undetectable levels by 90
      days; xymedone increased the proportion of surviving IB(4)+ neurons more than
      eight-fold. IB(4)+ neurons were more likely to enter post-traumatic apoptosis.
      Ligation of the nerve was followed by survival of fewer NF200+ and IB(4)+ neurons
      than section of the nerve, which suggests that axon lengthening is a factor
      maintaining neuron survival. The pyrimidine derivative xymedone increased the
      survival of neurons of both subpopulations, especially IB(4)+ neurons.

PMID- 15739786
TI  - Structural-metabolic organization of field 4 of the cat brain in normal
      conditions and after unilateral enucleation of the eye.
AB  - Comparative data on the structural-metabolic organization of field 4 of the cat
      brain in normal conditions and after unilateral enucleation of the eye are
      presented. Cytochrome oxidase was detected histochemically. Data were processed
      by a computerized method using an original video capture system. Data were
      obtained demonstrating the uneven distribution of enzyme along sublayer IlIb of
      field 4 in animals with unilateral enucleation. A hypothesis based on published
      data is suggested whereby the alternation of high- and low-reactive areas is
      evidence for the ordering of the retinal representations of the right and left
      eyes in the sensorimotor cortex.

PMID- 15739787
TI  - Plastic reorganization in the cerebellothalamic system after partial
      deafferentation of the ventrolateral nucleus of the thalamus.
AB  - A method based on the retrograde axonal transport of horseradish peroxidase after
      preliminary (three months) lesioning of the contralateral intermediate nucleus of
      the cerebellum or lateral vestibular nucleus of Deiters in adult cats
      demonstrated the formation of new ipsilateral thalamic projections from all three
      central nuclei of the cerebellum and the nuclei of the vestibular complex.

PMID- 15739785
TI  - Unipolar brush cells--a new type of excitatory interneuron in the cerebellar
      cortex and cochlear nuclei of the brainstem.
AB  - Published data and the authors' own studies on the morphology, neurochemical
      specialization, and spatial organization of unipolar brush neurons (UBN) in the
      cerebellar cortex and cochlear nuclei of the brainstem are reviewed. UBN
      represent an exclusive category of excitatory interneurons, with a single
      dendrite which forms a compact branching with a shape reminiscent of that of a
      brush in its terminal segment. These cells are characterized by an uneven
      distribution in the granular layer of the cerebellum, being located mainly in its
      vestibular zones. UBN synthesize glutamate, calretinin, and metabotropic and
      ionotropic glutamate receptors. The dendritic brush of UBN form giant synapses
      with the rosettes of glutamatergic and cholinergic mossy afferent fibers. UBN
      axons form an intracortical system of mossy fibers which, forming rosettes and
      glomeruli, make contact with the dendrites of other UBN and granule cells. In the
      circuits of interneuronal communications, UBN can be regarded as an intermediate
      component, amplifying the excitatory effects of mossy afferent fibers on granule
      cells in the cerebellar cortex and cochlear nuclei of the brainstem.

PMID- 15739788
TI  - The effects of direct sequential masking on evoked potentials in the auditory
      area of the cortex in guinea pigs.
AB  - Thresholds for the appearance of evoked potentials to clicks in test series were
      determined in the quiet and in conditions of sequential masking of one stationary
      and four moving sound images. Differences in the thresholds for the appearance of
      evoked responses to signals in the quiet and in the presence of the marker were
      taken as a measure of the extent of masking. The overall responses of the
      auditory area of the guinea pig cortex showed direct masking as a clear reduction
      in the magnitude of the response to the first click in the series as compared
      with the response in the quiet. The extent of masking decreased with increases in
      the time delay and was independent of the position of the sound image
      corresponding to this click in different test signals. This observation may
      provide indirect support for the hypothesis that the initial part of the signal
      is subject to greater masking than the final part. The magnitude of responses to
      subsequent clicks in series were determined by a combination of two factors--the
      action of the sequential masker in the "masker-signal" system and the interaction
      between the responses to individual clicks in the series making up the test
      signal.

PMID- 15739789
TI  - Hazard functions and expected spike density functions for neuron spike activity
      in the cochlear nucleus of the cat.
AB  - The goal of these experiments was to evaluate the effect of stimulus evoked input
      and post spike refractoriness on the shapes of post stimulus time histograms
      (PSTHs). The time courses of spontaneous and/or evoked activity were studied in
      153 neurons located predominantly in the dorsal cochlear nucleus in cats
      anesthetized with Nembutal. Tone bursts were presented to the ipsilateral ear in
      a free sound field. About half the cells were characterized by the pauser/build
      up type of PSTH. Marked refractoriness was evidenced by relatively long recovery
      times of the hazard functions of spontaneous and tone-evoked spike activity. On
      presentation of tonal bursts, the time dependence of the probability of the first
      spike in the absence of a preceding spike (expected spike density function) was
      greater than the PSTH (actual spike density function). The initial PSTH peak with
      pause was shaped primarily by stimulus evoked input, whereas refractoriness
      tended to diminish the build-up portion of the PSTH. In chopper cells, PSTH peaks
      were usually not reflected in expected spike density functions showing that post
      spike refractoriness plays a major role in shaping the PSTH. In primary-like
      cells, refractoriness was small and had little effect on the shape of the PSTH.
      Some presumptively inhibitory cells showed a tendency to burst discharges with
      non-monotonic hazard functions. A very small number of cells showed a tendency to
      internal tuning to a defined signal periodicity.

PMID- 15739791
TI  - The optical-geometrical characteristics and thresholds of perception of
      fragmented outline figures.
AB  - Measurements were made of the threshold of recognition of cumulatively forming
      line figures. The threshold value of the outline, expressed in pixels, depended
      on the length of the outline of the whole unfragmented figure. Relative threshold
      values were constant, and for the measures of figure fragments used in the
      present study, averaged 12.5%. A spatial frequency analysis of the test images
      was performed. Variation of the amplitude-frequency parameters of the spectra of
      the images of various figures with threshold fragmentation was minimal as
      compared with the variation of these parameters in figures with subthreshold or
      suprathreshold levels of fragmentation.

PMID- 15739790
TI  - Dynamic encoding of amplitude-modulated sounds at the level of auditory nerve
      fibers.
AB  - The relationship between the mean spike frequency of auditory nerve fibers and
      the levels of tonal stimuli with frequencies equal to the characteristic
      frequency can be presented as the "input-output" characteristic. In real auditory
      nerve fibers, the slope of this characteristic increases and its width decreases
      with increases in the level of spontaneous activity or the ability of fibers to
      generate spikes in the absence of a stimulus. However, real fibers with low
      spontaneous activity reproduce the amplitude modulation of sinusoidally amplitude
      modulated signal significantly better than fibers with high levels of spontaneous
      activity. The simulation experiment reported here shows that the reason for the
      good reproduction of amplitude modulation in auditory nerve fibers is not the
      static profiles of the "input-output" characteristic but the dynamic properties
      of fibers which support the tuning (adaptation) of the threshold of the fiber to
      the level of the stimulus being applied. Because of their steep "input-output"
      characteristic, auditory nerve fibers with high levels of spontaneous activity
      can reproduce the modulation of sounds at subthreshold levels when a weak noise
      is added to the signal, thus demonstrating the property of stochastic resonance.

PMID- 15739792
TI  - Habituation of horizontal nystagmus of the eyes in pigeons in conditions of
      alternating central and eccentric rotations.
AB  - Intact pigeons (n=19) were rotated in the dark in the horizontal plane in
      different orientations relative to the axis of rotation. In central (evoking
      habituation) rotations, the animal's head was located on the axis of rotation; in
      eccentric rotations, the animal's head was 0.6 m from the axis of rotation.
      Pigeons were subjected to series of alternating central and eccentric rotations;
      rotation directions were also alternated. Series consisted of 2-5 rotation using
      a trapezoidal program. Each stimulus evoking habituation was used no more than 14
      times during the experiment. Eccentric rotations were found not to prevent the
      gradual decrease in the peak rates of the slow components of primary nystagmus
      occurring on the transition from one series of central rotations to another in 17
      individuals (group 1); these were increased in two individuals (group 2). Group 1
      showed direct relationships between changes in this measure of primary nystagmus,
      changes in the duration of nystagmus, and changes in the peak rates of secondary
      nystagmus. Modifications of nystagmus within series varied. When two identical
      stimuli did not follow immediately one after the other, the second stimulus
      induced the same changes in nystagmus as observed in the individual in the first
      and next series of central rotations. If two identical stimuli followed one
      immediately after the other, the second stimulus in the pair often induced
      increases in the peak rates of primary and secondary nystagmus, along with
      increases in the time taken to reach the peak rate of primary nystagmus. These
      changes were non-random at a probability of >95%.

PMID- 15739793
TI  - Postvibration changes in the spike activity of neurons in the medial vestibular
      nucleus.
AB  - Changes in the baseline spike activity in the medial vestibular nucleus were
      studied after exposure to vibration for 5, 10, and 15 days. Studies addressed the
      distributions of neurons within this structure in terms of the regularity of
      their spike activity, the dynamics of neural flows, and the modalities of
      interspike histogram modalities. Mean values were calculated for the major
      statistical measures of baseline spike activity. Statistically significant
      changes in the major characteristics of neuron activity were seen in the medial
      vestibular nucleus at different periods of vibration exposure. Vibration was
      found to induce complex dynamic rearrangements in the baseline activity of
      neurons in this structure. The characteristics and functional significance of the
      results are discussed.

PMID- 15739794
TI  - The effects of moving sound images on postural responses and the head rotation
      illusion in humans.
AB  - The results of pilot studies on the effects of sound images moving in the
      horizontal plane on poststimulus responses and the head rotation illusion are
      presented. These phenomena are demonstrated to occur.

PMID- 15739796
TI  - Intravenous medication safety systems help prevent harm and career-ending
      mistakes. Extensive nursing input helps design easy-to-use system that intercepts
      critical errors.

PMID- 15739795
TI  - Sensory responses of neurons in the medial septal area in conditions of
      modulation of theta activity using the alpha-2-adrenoreceptor agonist clonidine.
AB  - Our previous studies on conscious rabbits showed that administration of the alpha
      2-adrenoreceptor agonist clonidine induces dose-dependent changes in theta
      oscillations in the septohippocampal system. Low doses of clonidine suppressed
      theta activity, while high doses produced significant potentiation. It was
      suggested that the different effects of clonidine might be associated with
      differences in the sensitivities of pre- and postsynaptic alpha-2-adrenoreceptors
      to clonidine, this agent being a pure agonist of noradrenaline when used at high
      doses. It was suggested that functional synergism occurs between the activatory
      reticular formation and the noradrenergic system of the locus ceruleus in
      controlling the theta rhythm. The present study was performed to identify the
      nature of the responses of sensory neurons in the medial septal region in
      conditions of alterations in the magnitude of the theta rhythm induced by
      different doses of clonidine. Low and high doses of the agonist given bilaterally
      into the lateral ventricles were found to have different effects on the sensory
      responses of neurons in the medial septal region. Injection of small clonidine
      doses (0.5 microg in 5 microl into each lateral ventricle), which decrease theta
      activity, was found to lead to weakening of activatory processes and enhancement
      of inhibitory processes in the medial septal region. The number of activatory
      responses decreased significantly and persisting responses were significantly
      weakened; inhibitory responses, conversely, were seen more frequently and were
      significantly more marked. Administration of high clonidine doses (5 microg in 5
      microl), which produce sharp increases in theta oscillations, led to significant
      reductions in the reactivity of cells in the medial septal region to sensory
      stimuli (from 76.8% in controls to 45% after clonidine), regardless of the nature
      of the initial responses. Persisting activatory and inhibitory responses were in
      most cases less marked than the initial responses. These results suggest that
      alpha-2-adrenoreceptors are involved in controlling the sensory reactivity of
      neurons in the medial septal region. The impairment of the normal processing of
      sensory stimuli seen during the continuous generation of rhythmic activity
      provoked by injection of large clonidine doses supports the role of the theta
      rhythm in the septohippocampal system as an active filter during the processing
      and recording of information.

PMID- 15739797
TI  - Prioritizing safety technologies. I.v. medication safety system offers greatest
      "speed to impact".

PMID- 15739798
TI  - Achieving rapid implementation without disrupting workflow. Medication
      administration technology meets nurses' need for "perfect" technology.

PMID- 15739799
TI  - Correcting risk of harm from i.v. medication errors. Explore safety, financial,
      and community benefits.

PMID- 15739800
TI  - Evidence-based improvements prevent high-risk errors. Harm isn't random.

PMID- 15739802
TI  - Potential toxicity of nonregulated asbestiform minerals: balangeroite from the
      western Alps. Part 2: Oxidant activity of the fibers.
AB  - The asbestiform mineral balangeroite [(Mg,Fe2+,Fe3+,Mn2+)42Si16O54(OH)36], whose
      toxic potential is unknown, is associated with chrysotile asbestos in the western
      Alps (Balangero mine, Piedmont, Italy). In order to examine whether such fibers
      may contribute to the oxidative damage produced by local asbestos dusts when
      inhaled, balangeroite was studied by means of both cell-free and cellular tests,
      comparing the results with those concerning the most pathogenic asbestos form,
      crocidolite. Similarly to the crocidolite surface, iron was mobilized from
      balangeroite by chelators, to a different extent: deferoxamine > ascorbic acid >
      ferrozine. Poorly coordinated surface ions, as evaluated from the adsorption of
      NO as a probe molecule (by both calorimetry and infrared spectroscopy), are even
      more abundant on balangeroite than on crocidolite. The spin trapping technique
      shows that surface iron-derived Fenton activity (HO* from H2O2) is similar for
      the two fiber types, while a pretreatment in ascorbic acid, by reducing
      previously oxidized surface iron, activates the potential to cleave a C-H bond
      (yielding *CO2- from formate anion). Balangeroite, like crocidolite, produces
      nitrite accumulation, lipid peroxidation, and NO synthase activation in a human
      lung epithelial cell line (A549). All these findings, regarded as features
      related to the toxic potential of asbestos, suggest that balangeroite may be a
      potentially hazardous fiber per se and could be partly responsible for lung
      diseases reported in epidemiological studies in exposed miners.

PMID- 15739801
TI  - Potential toxicity of nonregulated asbestiform minerals: balangeroite from the
      western Alps. Part 1: Identification and characterization.
AB  - In the Italian western Alps, asbestos mineralization (both chrysotile and
      tremolite amphibole) takes place from serpentinites, together with other less
      common asbestiform minerals not regulated by the current legislation. In the
      context of a study on the evaluation of the asbestos risk in this area, the
      possible role played by the associated asbestiform minerals in the overall
      toxicity of the airborne fraction has been examined. The first mineral
      investigated was balangeroite [(Mg,Fe2+,Fe3+,Mn2+)42Si16O54(OH)36], an iron-rich
      asbestiform contaminant of chrysotile from the Balangero mine (Piedmont), which
      crystallizes as rigid and brittle fibers. In order to prepare a sample in a form
      appropriate for chemical and cellular tests, the fibers were separated from the
      rock and comminuted without damage to their crystalline structure and surface
      state (as confirmed by X-ray diffraction [XRD] and ultraviolet-visible [UV-Vis]
      spectroscopy). The first properties examined were durability in simulated body
      fluids (Gamble's solution) and toxicity to epithelial cells. When compared to
      UICC crocidolite (the amphibole blue asbestos, regarded as the most pathogenic
      form), balangeroite appears even more durable than crocidolite. Balangeroite and
      UICC crocidolite showed a similar in vitro cytotoxic effect on a human epithelial
      cell line, as evidenced by leakage of intracellular lactate dehydrogenase (LDH)
      activity, which, observed after a 24-h incubation, was dose dependent and maximal
      at 12 microg/cm2 for each fiber type. Data show that chemical composition, form,
      durability, and cell toxicity indicate balangeroite as a potentially harmful
      fibrous mineral that needs to be examined by further chemical and cellular tests.

PMID- 15739803
TI  - Potential toxicity of nonregulated asbestiform minerals: balangeroite from the
      western Alps. Part 3: Depletion of antioxidant defenses.
AB  - The asbestiform fibrous silicate balangeroite exhibits cytotoxic and oxidative
      properties similar to those exerted by crocidolite asbestos. In human lung
      epithelial cells A549, balangeroite, like crocidolite, inhibited the pentose
      phosphate pathway (PPP), one of the main antioxidant intracellular tools; this
      inhibition was exerted also when PPP was activated by the redox-cycling compound
      menadione. PPP inhibition may be accounted for by the inhibition of its rate
      limiting enzyme, glucose-6-phosphate dehydrogenase (G6PD). Reduced glutathione
      (GSH), the most important intracellular antioxidant molecule, was decreased by
      both balangeroite and crocidolite incubation. This effect was not related to any
      increased content of oxidized glutathione, or to any enhanced efflux of
      glutathione, suggesting that balangeroite fibers, like crocidolite, might favor
      the reaction of GSH with other molecules.

PMID- 15739804
TI  - Bioaccumulation of DDT pesticide in cultured Asian seabass following dietary
      exposure.
AB  - Bioaccumulation and metabolism of p,p'-DDT was studied in the marine carnivorous
      fish Lates calcarifer, Asian seabass, in a controlled aquaculture experiment.
      Over a 42-d period, seabass were fed pellets dosed with p,p'-DDT at
      environmentally realistic levels. Virtually all p,p'-DDT in pellets
      bioaccumulated in the fish with an uptake efficiency of 98%. The levels of p,p'
      DDT and the metabolites p,p'-DDD and p,p'-DDE were analyzed in muscle, liver,
      visceral fat, brain, and remaining tissues. Partitioning of p,p'-DDT and its
      metabolites among the control, low-dose, and high-dose exposed seabass were 14.8%
      in muscle, 3.5% in liver, 37.1% in visceral fat, 0.11% in brain, and 45.5% in
      remaining tissues, where partitioning between tissues was a function of tissue
      lipid content. p,p'-DDT bioaccumulation increased linearly with exposure in
      visceral fat and muscle tissue. The metabolism of p,p'-DDT, which occurs mainly
      in the liver, resulted in the degradation of 2.5% of p,p'-DDT into p,p'-DDD.
      These new findings show that bioaccumulation processes at environmentally
      realistic ingestion exposure levels (ng/g) differ from previous DDT ingestion
      studies conducted at unrealistically high DDT levels (microg/g), highlighting the
      need to revise models on the transfer of persistent organic pollutants in the
      marine environment and aquaculture systems.

PMID- 15739805
TI  - A toxic extract of the marine phytoflagellate Prymnesium parvum induces calcium
      dependent release of glutamate from rat brain synaptosomes.
AB  - Blooms of the marine phytoflagellate Prymnesium parvum produced mass mortality of
      fish in Norway and many other parts of the world. The effects of a purified algae
      extract of P. parvum on transmitter release from rat brain synaptosomes were
      studied to characterize its toxic action. Synaptosomes are detached nerve
      terminals and represent a simple system that has retained the machinery for
      uptake, synthesis, storage, and release of neurotransmitters. A crude methanol
      extract of P. parvum was purified by reverse-phase column for fast protein liquid
      chromatography (FPLC). The purified extract stimulated Ca2+-dependent spontaneous
      release of glutamate in a concentration-dependent manner. The release was
      increased by addition of extracellular Ca2+. The release of glutamate was
      suppressed by the Ca2+-channel blockers flunarizine (10 microM), diltiazem (10
      microM), and verapamil (10 microM). The stimulation of release of glutamate from
      rat brain synaptosomes induced by the toxin may be due to an ionophorelike
      property of the algae extract such as previously reported for the potent algal
      toxin maitotoxin. At high concentrations the toxin primarily acts as a powerful
      lytic agent.

PMID- 15739806
TI  - Official position of the division of clinical neuropsychology (APA division 40)
      on the role of neuropsychologists in clinical use of fMri: approved by the
      Division 40 Executive Committee July 28, 2004.

PMID- 15739807
TI  - Self-awareness of deficits in Parkinson disease.
AB  - Anosognosia is an unawareness or denial of deficits. While it has mainly been
      associated with damage to cortical brain regions, anosognosia has also been
      reported in patients with subcortical brain disease. The present study
      investigated whether anosognosia is a feature of Parkinson disease. Forty-eight
      Parkinson disease patients with predominantly left- (N = 16) or right-sided (N =
      32) motor symptoms who eventually underwent right or left pallidotomies, and 48
      individuals identified as caregivers completed questionnaires rating severity of
      PD. There was no discrepancy in report between patients and caregivers as a
      function of pallidotomy side. However, as a group, patients rated themselves as
      significantly less impaired on 2 measures of activities of daily living,
      indicating that basal ganglia dysfunction may alter insight into severity of
      illness. Patients and caregivers in the left-symptom PD group differed
      significantly on selected measures of functional independence. This suggests the
      potential interaction of laterality and handedness. The importance of future
      investigations in PD patients with more severe cognitive impairment is stressed.

PMID- 15739808
TI  - Neuropsychological evaluation of mild cognitive impairment: three case reports.
AB  - Recent research on mild cognitive impairment (MCI) has focused on the description
      of the disorder, its biological markers, and conversion rates to dementia.
      Studies of cognitive deficits in individuals who present with memory decline but
      do not fulfill criteria for dementia have analyzed baseline group data according
      to outcome diagnosis. The application of these findings to the individual person
      remains problematic. The current article presents three cases with a relatively
      isolated deficit in memory for word lists but better performance on other memory
      tests. Questions arising with regards to the MCI criteria are discussed in light
      of these case reports.

PMID- 15739809
TI  - Normative data for determining significance of test-retest differences on eight
      common neuropsychological instruments.
AB  - Clinicians and researchers who use neuropsychological tests to track functioning
      over time are in need of a method to correct for the effects of practice. Drawing
      from a large database of healthy, male subjects, we present data that can be used
      to calculate predicted retest scores for eight widely used neuropsychological
      instruments either via simple regression or reliable change index (RCI) methods.
      These methods are useful for individuals assessed across a wide time interval, 4
      24 months. Limitations are discussed regarding the applicability of the data.
      Those with a need to factor out the effects of practice, test-retest reliability
      and other statistical confounds will find the information within this article
      useful.

PMID- 15739810
TI  - Influence of age, sex, and education on the Visual Object and Space Perception
      Battery (VOSP) in a healthy normal elderly population.
AB  - The assessment of visual perception and cognition forms an important part of any
      general cognitive evaluation. We have studied the possible influence of age, sex,
      and education on a normal elderly Spanish population (90 healthy subjects) in
      performance in visual perception tasks. To evaluate visual perception and
      cognition, we have used the subjects performance with The Visual Object and Space
      Perception Battery (VOSP). The test consists of 8 subtests: 4 measure visual
      object perception (Incomplete Letters, Silhouettes, Object Decision, and
      Progressive Silhouettes) while the other 4 measure visual space perception (Dot
      Counting, Position Discrimination, Number Location, and Cube Analysis). The
      statistical procedures employed were either simple or multiple linear regression
      analyses (subtests with normal distribution) and Mann-Whitney tests, followed by
      ANOVA with Scheffe correction (subtests without normal distribution). Age and sex
      were found to be significant modifying factors in the Silhouettes, Object
      Decision, Progressive Silhouettes, Position Discrimination, and Cube Analysis
      subtests. Educational level was found to be a significant predictor of function
      for the Silhouettes and Object Decision subtests. The results of the sample were
      adjusted in line with the differences observed. Our study also offers preliminary
      normative data for the administration of the VOSP to an elderly Spanish
      population. The results are discussed and compared with similar studies performed
      in different cultural backgrounds.

PMID- 15739811
TI  - Confirmatory factor analysis of the behavioral dyscontrol scale in a mixed
      clinical sample.
AB  - The Behavioral Dyscontrol Scale (BDS) is a brief measure of executive functioning
      originally designed for use primarily with older adults. Previous research
      suggests that factors derived from exploratory factor analysis of the BDS have
      clinical utility and are theoretically meaningful; however, the factor structure
      has not been previously submitted to confirmatory analysis, and there are several
      potential methodological problems with the previous exploratory factor analysis.
      In this study, we conducted a confirmatory factor analysis of the BDS. Findings
      were largely consistent with the original exploratory analysis (Grigsby, Kaye, &
      Robbins, 1992) in suggesting a three-factor model, although the three-factor
      model was a better fit if factors were allowed to correlate with one another. The
      findings of this study lend support to the current practice of using factor
      scores in clinical and research applications.

PMID- 15739812
TI  - The development of a trial making test in young children: the TRAILS-P.
AB  - Preschool children have a more limited verbal repertoire, less proficient manual
      skills, and more variable attention spans relative to those of school age, with
      comparatively few neuropsychological tasks available for use in this age range. A
      prototypic neuropsychological test, the Trail Making Test, was adapted for use
      with young children, the TRAILS-P, using a developmentally salient storybook
      format with colorful stimuli in differing conditions with varying executive
      demands. The TRAILS-P was administered to 103 normally developing preschoolers
      between 2 and 6 years of age; 30 of these children were retested within one month
      to determine test reliability. Correlations among latencies to complete each
      condition and condition errors generally were moderate to high, suggesting
      coherence in test content. There also was evidence for good test-retest
      reliability. Latency to complete the TRAILS-P conditions differed as a function
      of the interaction of condition type and age group. Although the youngest
      children generally took more time to complete all TRAILS-P conditions, 3-year-old
      children were disproportionately slow to complete the condition that required
      shifting between stamping stimuli of two classes, with distraction by the
      additional presence of irrelevant stimuli. In contrast, the number of errors
      differed only in the 5-year-olds relative to younger children. These findings
      suggest that executive abilities can be assessed adequately in young children
      when tasks are designed to take advantage of the developmentally unique features
      of the preschool period.

PMID- 15739813
TI  - Evaluation of two methods for estimating Premorbid Intelligence on the WAIS-III
      in a clinical sample.
AB  - Two methods of predicting premorbid WAIS-III Full Scale IQ, namely a demographic
      measure (DP IQ) and the Oklahoma Premorbid Intelligence Estimate-3 (OPIE-3), were
      assessed in three traumatic brain injury (TBI) groups of varying injury severity
      and normal controls. On the DP IQ, average scores were in keeping with the
      general population mean across all groups but range was severely restricted. OPIE
      3 IQ scores were not subject to severe range restriction and were comparable with
      the general population mean in the control and least severely brain injured
      group. They were significantly lower relative to controls in the severe and
      extremely severe TBI groups, with differences averaging around 7 and 10 points,
      respectively. OPIE-3 (Best) proved particularly robust in more severely injured
      subjects. Effect sizes for the combined TBI sample relative to controls were
      greatest for OPIE-3 measures that included two non-verbal subtests and were least
      for that involving vocabulary only. Implications of the findings for clinical
      practice and further research are discussed.

PMID- 15739814
TI  - Neuropsychological assessment of individuals with expressive disabilities in
      addition to traumatic brain injuries.
AB  - Little empirical research has examined guidelines for neuropsychological
      assessment of people with severe physical and sensory disabilities. This study
      focused on people with expressive disabilities--people unable to speak, write,
      draw, or manipulate test materials. Measures were selected and adapted to be
      suitable for the assessment of cognitive functioning for such people. Responses
      were selected from multiple choice answers or were spelled out on an alphabet
      board. Individuals with expressive disabilities in addition to traumatic brain
      injuiry (TBI) were compared to individuals with TBI alone and a normative group.
      The measures were generally found to be reliable and valid assessment
      instruments. Individuals with expressive disabilities were able to manage the
      task requirements of the adapted tests. The results provided support for the
      adaptations trialed.

PMID- 15739815
TI  - Methodological problems in the neuropsychological assessment of effects of
      exposure to welding fumes and manganese.
AB  - Recently, Kaiser (2003) raised concerns over the increase in brain damage claims
      reportedly due to exposure to welding fumes. In the present article, we discuss
      methodological problems in conducting neuropsychological research on the effects
      of welding exposure, using a recent paper by Bowler et al. (2003) as an example
      to illustrate problems common in the neurotoxicity literature. Our analysis
      highlights difficulties in conducting such quasi-experimental investigations,
      including subject selection bias, litigation effects on symptom report and
      neuropsychological test performance, response bias, and scientifically inadequate
      casual reasoning.

PMID- 15739816
TI  - The Rey AVLT Serial Position Effect: a useful indicator of symptom exaggeration?
AB  - This investigation explored the usefulness of serial position patterns during
      word recall on the Rey Auditory Verbal Learning Test (RAVLT; Rey, 1964) as an
      indicator of poor effort. Significantly better recall for early (primacy) and
      recent (recency) material defines the serial position effect (SPE; Rundus, 1971).
      The SPE on the RAVLT was examined in four groups: normal controls (NC), symptom
      coached simulators (SC), test-coached simulators (TC), and a group of moderate to
      severe subacute traumatic brain injury (TBI) patients. Normal control
      participants and TBI patients demonstrated the expected SPE. Only the SC
      simulators clearly suppressed the primacy effect. The SPE appears neither
      sensitive nor specific enough to be used independently of more sensitive symptom
      validity tests in the detection of suboptimal effort. It may be especially
      problematic when used with clients presenting with sophisticated styles of
      exaggeration and in settings with lower base rates of compromised effort.

PMID- 15739818
TI  - Transplacental passage of vancomycin in the ex vivo human perfusion model.
AB  - OBJECTIVES: To determine maternal-fetal transplacental passage of vancomycin in
      the ex vivo human placental perfusion model. METHODS: Six term placentas were
      collected immediately after delivery and perfused with physiologic medium using
      the single cotyledon perfusion system. Vancomycin was added to the maternal
      medium and perfused through the maternal circulation of the cotyledon. Over a 1-h
      period in an open system, samples of the perfusate were collected at defined
      intervals from the fetal venous catheter and from the maternal effluence to
      assess vancomycin transfer. Thereafter, the system was closed for 1-5 h to
      establish accumulation. Transport fraction and clearance indexes were calculated
      by perfusing antipyrine 14C (positive control). Vancomycin was estimated by high
      pressure liquid chromatography and antipyrine 14C concentration was determined by
      liquid scintillation. RESULTS: Mean vancomycin maternal peak and trough
      concentrations ranged from 30.0 to 51.5 microg/ml and 7.7 to 16.4 microg/ml,
      respectively. Clearance indexes were minimal with a mean peak range of 0.000
      0.080 and a mean trough range of 0.00-0.17. For each placenta, transport fraction
      for antipyrine 14C was > 1.85 with a single pass of > 40%. No accumulation of
      vancomycin was noted when the system was closed for 1-5 h. The mean peak
      clearance index was zero after perfusing the placenta for up to 5 h with 35.8
      microg/ml of vancomycin. CONCLUSION: Transplacental passage of vancomycin was
      minimal in the ex vivo human placental perfusion model, with no detectable
      accumulation.

PMID- 15739817
TI  - HPV prevalence and concordance in the cervix and oral cavity of pregnant women.
AB  - OBJECTIVES: This investigation examined human papillomavirus (HPV) in pregnant
      women in order to characterize viral prevalence, types and concordance between
      infection in the cervix and in the oral cavity. METHODS: A total of 577 pregnant
      women seeking routine obstetric care were evaluated for HPV infection in their
      cervix during gestation and immediately before delivery, and in the oral cavity
      during gestation. Male partners present during the gestational clinic visit also
      provided a specimen from their oral cavity. HPV assessment was performed by PCR,
      dot blot hybridization and DNA sequencing. A sexual and health questionnaire was
      completed by the pregnant women. RESULTS: HPV prevalence in women was 29% in the
      cervix and 2.4% in the oral cavity. Among those with both gestational and
      delivery specimens, 35% were infected at least once and 20% had infection at both
      intervals. At delivery, 68% of infected women had an oncogenic HPV type in the
      cervix. There was no type-specific HPV concordance between the two cervical
      specimens, nor cervical and oral results in women, nor with cervical and oral
      findings between partners. CONCLUSION: The lack of association in HPV positivity
      and types between the cervix and oral cavity in these women suggests that self
      inoculation is uncommon. This source of infection does not appear to be from oral
      contact with a current male partner, since there also was no concordance between
      partners. These results suggest either other modes of HPV transmission or
      differences in susceptibility to HPV infection or its clearance in the oral
      cavity and genital mucosa.

PMID- 15739819
TI  - Experience with routine vaginal pH testing in a family practice setting.
AB  - BACKGROUND: Despite recommendations by Centers for Disease Control and the
      American College of Obstetricians and Gynecologists, pH testing is infrequently
      performed during the evaluation of vaginitis. Consequently, little information
      exists on its use in a primary care setting. OBJECTIVE: The aim of this study was
      to describe our experience with routine pH testing, particularly the relationship
      between symptoms, pH and wet-mount microscopy. METHOD: A retrospective chart
      review was performed on 203 consecutive cases evaluated for vaginitis by wet
      mount microscopy. RESULTS: Of the 203 cases, 21 had normal pH and no symptoms and
      182 had symptoms, elevated pH or both; 85% of cases had abnormal wet-mount
      findings, including 75% with clue cells, 14% with Trichomonas vaginalis, 13% with
      yeast and 14% with mixed infections. Asymptomatic infection was present in 42% of
      cases with clue cells alone, 44% of cases with Trichomonas vaginalis alone, 38%
      of all trichomoniasis cases and 33% of cases with mixed infections. Elevated pH
      was associated with clue cells (p < 0.001), trichomoniasis (p = 0.01) and mixed
      infections (p = 0.003). Normal pH was associated with negative wet mount (p <
      0.001) and to a lesser degree with uncomplicated vulvovaginal candidiasis (p =
      0.06). CONCLUSION: Routine pH testing increased detection of trichomoniasis and
      bacterial vaginosis by prompting microscopy in a significant proportion of
      asymptomatic cases.

PMID- 15739820
TI  - Human parvovirus B19 VP2 empty capsids bind to human villous trophoblast cells in
      vitro via the globoside receptor.
AB  - BACKGROUND: Pregnant women acutely infected with human parvovirus B19 (B19) may
      transmit the virus to the developing fetus. The mechanism whereby the virus
      interacts with the placenta is unknown. It is known that globoside receptor is
      required for successful infection of the target cells, which are the highly
      undifferentiated, actively dividing colony and burst-form units of the erythroid
      series. Globoside is present on trophoblast cells which have intimate contact
      with maternal blood, and may therefore serve as a potential route for B19
      transmission into the fetal compartment. OBJECTIVES: The purpose of this study
      was to determine whether B19 VP2 capsids could bind to villous trophoblast cells
      in vitro and whether globoside was involved. METHODS: Binding of B19 VP2 empty
      capsid to first-trimester villous trophoblast cells was assessed by multiple
      approaches, including ICC using either biotinylated B19 VP2 empty capsid or
      unlabeled B19 VP2 empty capsid. Quantification of viral binding involved I125
      labeled B19 VP2 empty capsid. Competition studies included excess unlabeled empty
      capsids or pretreatment with globoside-specific IgM antibody. RESULTS: Linear
      binding of B19 VP2 capsid to purified villous trophoblast cells in vitro was
      clearly demonstrated (R2= 0.9524). Competition studies revealed specificity of
      I125-labeled B19 VP2 capsid binding to villous trophoblast cells when
      pretreatment with either 60-fold excess unlabeled B19 capsid or globoside
      specific IgM antibody took place. The results illustrated B19's ability to bind
      in a specific manner to globoside-containing villous trophoblast cells.
      CONCLUSION: We speculate that the globoside present on trophoblast cells may play
      a role in viral binding in vivo, which may facilitate B19 transmission across the
      maternal-fetal interface.

PMID- 15739821
TI  - Differential vaginal expression of interleukin-1 system cytokines in the presence
      of Mycoplasma hominis and Ureaplasma urealyticum in pregnant women.
AB  - OBJECTIVE: The genital mycoplasmas, Ureaplasma urealyticum and Mycoplasma
      hominis, are commonly identified in the vagina of healthy pregnant women.
      However, these microorganisms are the most common isolates from the amniotic
      fluids of women in preterm labor. The mechanisms responsible for vaginal
      colonization and ascent to the uterus remain undetermined. We evaluated the
      association between U. urealyticum and M. hominis vaginal colonization and the
      presence of pro-inflammatory and anti-inflammatory interleukin-1 system
      components in asymptomatic pregnant women of different ethnicities. METHODS:
      Vaginal specimens, obtained from 224 first trimester pregnant women, were assayed
      for interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra)
      concentrations by ELISA. U. urealyticum and M. hominis vaginal colonization were
      identified by polymerase chain reaction (PCR). RESULTS: Vaginal colonization with
      M. hominis was identified in 37 (16.5%) women, and was more prevalent in black
      (18.9%) and Hispanic (20.9%) than in white (4.2%) women (p = 0.01). U.
      urealyticum was present in 84 (37.5%) women and there was no ethnic disparity in
      its detection. M. hominis colonization was associated with elevated median
      vaginal IL-1beta concentrations in both black women (p = 0.02) and Hispanic women
      (p = 0.04), and was unrelated to vaginal IL-1ra concentrations. In marked
      contrast, U. urealyticum colonization was associated with elevations in vaginal
      IL-1ra levels, but not with IL-1beta concentrations, in black women (p = 0.02)
      and Hispanic women (p < 0.0001) and marginally in white women (p = 0.06).
      CONCLUSION: M. hominis colonization in healthy pregnant women is associated with
      localized pro-inflammatory immune activation, while U. urealyticum colonization
      is associated with immune suppression.

PMID- 15739822
TI  - Case report of a pelvic-peritoneal tuberculosis presenting as an adnexial mass
      and mimicking ovarian cancer, and a review of the literature.

PMID- 15739823
TI  - Usage of antifungal drugs for therapy of genital Candida infections, purchased as
      over-the-counter products or by prescription: I. Analyses of a unique database.
AB  - OBJECTIVES: To present sales figures of antifungal drugs for treatment of genital
      Candida infections in females, which had been purchased in the Swedish county of
      Skane (with approximately 1.2 million inhabitants) during the 1990s. To study the
      relative proportions of the drugs sold by prescription and as over-the-counter
      (OTC) products. METHODS: Sales figures of antifungal drugs for therapy of
      vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC), for the
      years 1990--99, were collected from the 'ACS' database of the National
      Corporation of Swedish Pharmacies. RESULTS: The study showed an increase in sales
      of the type of drugs studied from 45,000 packages in 1990 until mid-93/94, when
      approximately 70,000 packages were sold (mainly azoles for topical use and
      fluconazole for oral intake). Thereafter there was a decrease until the end of
      November 1999, when 54,000 packages were purchased. Of the total sales, 93% were
      OTC products. Sales of clotrimazole and econazole (for vaginal installation) in
      1993--1994 were equal to 85-90 packages/1000 women in the age group 15-45 years.
      Extremely high sales volumes of fluconazole and itraconazole, for one single year
      each, could be explained by marketing-related activities directed to the medical
      community. CONCLUSIONS: As many women with RVVC are not cured by iatrogenic
      initiatives and women consider themselves able to diagnose episodes of genital
      Candida infection, affected women generally turn to self-medication with
      antifungal OTC products. This stresses the role of pharmacy counseling. Short
      term marked alterations in sales volumes may be due to marketing factors rather
      than changes in the epidemiology of genital Candida infections.

PMID- 15739824
TI  - Usage of antifungal drugs for therapy of genital Candida infections, purchased as
      over-the-counter products or by prescription: 2. Factors that may have influenced
      the marked changes in sales volumes during the 1990s.
AB  - BACKGROUND: The epidemiology of vulvovaginal candidiasis (VVC) and such recurrent
      infections (RVVC) has been difficult to study as the majority of episodes of
      these conditions are self-treated by the women affected. In Sweden, all
      pharmacies are owned by the state and all prescriptions and over-the-counter
      (OTC) products, such as antifungals, are registered in a database, which offers
      unique possibilities to study the epidemiology of VVC/RVVC. OBJECTIVES: To
      analyze all prescriptions and OTC products purchased for therapy of VVC/RVVC and
      to establish reasons for any observed variation in the sales figures. METHODS:
      Sales figures in the Swedish county of Skane of antifungal drugs for therapy of
      VVC/RVVC were analyzed by the aid of the 'ACS' database of the National
      Corporation of Swedish Pharmacies for the years 1990--1999. The size of the
      female population in the county is approximately half a million. RESULTS: The
      study showed that 93% of all antifungal drugs for VVC/RVVC were sold as OTC
      products. An increase in sales of the drugs occurred until mid- 1993/94, followed
      by a decrease until end of the study period in 1999. Demographic factors (e.g.
      the number of female inhabitants in the county, pharmacies and health-care
      units), the pregnancy rate and pharmacy-dependent factors (such as the
      introduction of shelves for self-selection of antifungal products) did not
      explain the observed variations in sales. Distinct short-term variations in the
      number of prescriptions of fluconazole and itraconazole could be explained by
      drugs company sales campaigns and logistics factors in drug distribution. The
      sales volumes in the 33 municipalities in the county correlated with the density
      of the population, which was not the case for the total number of prescriptions
      made in the county during the 1990s. The variation in antifungal drug sales was
      similar to that of hormonal intrauterine devices, but this was not the case for
      oral contraceptives. The total Swedish usage of antibiotics showed a similar
      variation to that of the antifungal drugs analyzed. CONCLUSION: The study
      stresses the limited impact on the treatment of VVC/RVVC by the medical
      community. Behavior-related factors in the female population are the most likely
      explanation for the marked variations found in the usage of drugs for the two
      conditions.

PMID- 15739825
TI  - Measuring social aspects in the physician/patient relationship.
AB  - This study develops a scale assessing social aspects of physician/patient
      relationships across multiple samples. The 6-item Social Aspects of Professional
      Service Relationships (SAPSR) scale demonstrates face validity through
      correspondence with theoretical constructs--including functional quality,
      communal behaviors, and affective care--and elements identified in qualitative
      interviews. The scale performs well in three separate samples. Relationships
      between SAPSR and re-patronization intentions and recommendation intentions that
      are partially mediated by satisfaction suggest the predictive validity and
      potential managerial utility of the scale.

PMID- 15739826
TI  - Media credibility and informativeness of direct-to-consumer prescription drug
      advertising.
AB  - In this article, we report the results of a study conducted to determine consumer
      perceptions of the media credibility and informativeness of direct-to-consumer
      prescription drug advertising (DTC advertising) and to examine how those
      perceptions are influenced by consumer predispositions and demographic
      characteristics, especially consumer age. This study specifically surveyed older
      consumers, who are the most significant market segment for prescription drugs and
      particularly susceptible and vulnerable to commercial persuasion. Older
      consumers' perceptions of DTC advertising were found to be neutral but their
      evaluation of informativeness was found to be more positive. Attitude toward DTC
      advertising and DTC advertising familiarity predicted perceived credibility
      across various media and attitude toward DTC advertising was the most prominent
      predictor of perceived informativeness. Age and usage of different media were
      also found to predict credibility and informativeness of DTC advertising in
      certain types of media. This study's findings provide insight into how older
      consumers evaluate various DTC advertising media as an information source.

PMID- 15739827
TI  - The role of attitudes and self-efficacy in predicting condom use and purchase
      intentions.
AB  - This study examines the condom purchasing and use habits of 256 college students
      in Norway and English-speaking Canada, and develops a structural equation model
      to explain condom purchase and use. In the model, intention to purchase condoms
      is influenced by self-efficacy in condom purchasing, as well as by intention to
      use condoms. Intention to use condoms is influenced by having a positive attitude
      toward condom usage and by self-efficacy in persuading a partner to use condoms.
      The implications for health promotion and social marketing campaigns are
      discussed.

PMID- 15739828
TI  - Risk avoidance versus risk reduction: a framework and segmentation profile for
      understanding adolescent sexual activity.
AB  - The teen birthrate in the United States is twice that of other industrialized
      nations. Adolescents in the U.S. are among high-risk groups for HIV/AIDS and
      other sexually transmitted diseases. As a result, the Department of Health and
      Human Services changed its policy on the promotion of abstinence to teenagers
      from a focus on a risk reduction strategy to a focus on a risk avoidance
      strategy. In order to create more effective risk avoidance as well as risk
      reduction campaigns, this study proposes a framework to illustrate the
      distinction that teens make between spontaneous sexual activity and planned
      sexual activity, as well as those teens that make a commitment to abstinence
      versus abstinence by default. Furthermore, this study classifies teens into three
      behavior segments (abstemious, promiscuous and monogamous) and then assesses
      specific differences that exist within these groups relative to their attitudes
      and perceptions concerning abstinence, sexual activity, contraception, fear and
      norms. This change in focus from a risk reduction to a risk avoidance strategy
      has important implications for social marketing, public policy and marketing
      theory.

PMID- 15739829
TI  - Priming and the predictability of contextual information.
AB  - Past research has indicated that repetition priming is disrupted by variable
      contextual information such as word-to-word changes in voice. In three
      experiments, we examined whether subjects' prediction of contextual changes could
      attenuate this effect. Predictability of contextual changes was accomplished
      either by presenting speakers' voices in a fixed sequential order or by giving
      subjects prior knowledge of which voice would produce the next word. In these
      experiments, predictability attenuated the disruptive effect that changes in
      voice had on priming, suggesting the processes which underlie this memory
      phenomenon are modulated by expectations that selectively optimize subjects'
      processing of incoming information.

PMID- 15739830
TI  - Chemosensory loss in adults aging with HIV.
AB  - Given that gustatory and olfactory impairments occur with Human Immunodeficiency
      Virus (HIV) and the normal aging process, people aging with HIV may experience
      considerable chemosensory losses. Declines may place such adults at risk for
      eating contaminated foods, malnutrition, cognitive complaints, and reduced
      quality of life. Implications for study and treatment are considered.

PMID- 15739831
TI  - Modalities of submaximal exercises on ratings of perceived exertion by young
      girls: a pilot study.
AB  - This pilot study compared the rating of perceived exertion scores (RPE) in young
      girls for two modalities of exercises (running vs cycling) performed at the same
      absolute heart rate. 23 girls, ages 8 to 11 years, from a gymnastic club
      performed graded, intermittent, and submaximal running and cycling exercises at a
      similar absolute heart rate (+/-5 bpm). These exercises consisted of three stages
      of 3 min. duration separated by 1-min. recovery intervals. RPE was estimated
      using the Children's Effort Rating Table scale at the end of each stage of each
      exercise. Mean ratings were only significantly different during cycling, compared
      to running for the Stage 3 (cycling 5.3+/-2.7 and running 7.0+/-1.9, p < .05).
      During low exercise intensity, measured as heart rate, the modality of exercise
      does not seem to affect RPE. In contrast, with high heart rates, RPE are higher
      during cycling than running, so it is necessary to take account of the type of
      exercise.

PMID- 15739832
TI  - Mormon and Jewish views of the afterlife.
AB  - In their responses to a questionnaire, undergraduates, 60 Mormons, viewed the
      afterlife as less pleasant than did the 37 Jews, while the Jews were more
      concerned with sin and judgment and more often believed in reincarnation.

PMID- 15739833
TI  - Test-retest reliability of the self-assessed physical activity checklist.
AB  - To estimate the test-retest reliability of a modified version of the Self
      assessed Physical Activity Checklist two administrations separated by 5 days were
      conducted for 52 boys and 51 girls in Grade 6 in Australia. Intraclass
      correlation coefficients were calculated to assess the reliability. Similar test
      retest reliabilities were found between boys and girls for light, moderate, and
      total physical activity, with the largest difference for vigorous physical
      activity (.44 vs .12). The results suggest that the checklist is a more
      appropriate measure of boys' physical and sedentary activity as boys reported
      higher reliability coefficients on all categories except for light physical
      activity and TV/Video watching.

PMID- 15739834
TI  - Rate of learning and asymptotic performance in an automatization task and the
      relation to reading.
AB  - In the present study, direct evidence was sought linking cognitive automatic
      processing with reading in the general adult population. Reading speed on single
      task performance and dual-task performance were compared. A total of 18 adults
      without dyslexia participated (7 men and 11 women, age M=25.3 yr., SD=2.7).
      Participants initially were trained in single-task mode on two types of tasks.
      The first was a central alphanumeric equation task (true or false), which
      comprised 3 subtests of increasing difficulty, ranging from an easily automated
      task to a varied and unpredictable mathematical operation. The second task was a
      peripheral pattern subitization task for which stimulus exposure time was related
      to performance. Finally, participants received dual-task training, which required
      simultaneous processing of both tasks. Slower reading speed was significantly
      related to rate of learning and speed of performance on predictable alphanumeric
      operations in dual-task conditions. There was no effect of reading speed on
      performance in the varied alphanumeric task. Faster readers were no better than
      slower readers on the pattern-subitization task. These findings suggest that
      faster readers automatized the predictable alphanumeric task more rapidly than
      slower readers and hence were better able to cope with the dual-task condition.

PMID- 15739835
TI  - False recall for people's names in the Deese-Roediger-McDermott Paradigm:
      conspicuousness and semantic encoding of the critical lure.
AB  - The Deese-Roediger-McDennott (DRM) paradigm for studying false recall uses
      people's names as critical lures. In this study the contextual organization of
      list structure was manipulated in an effort to make the critical lure's absence
      inconspicuous and consequently increase the likelihood of false recall of the
      critical lures. Following Bredart's 2000 work, a list structure that appears to
      make the critical lure inconspicuous was constructed (Inconspicuous lure
      structure), according to the characteristics of two lists that previously induced
      a number of false memories. The rate of false recall for this structure was
      compared with Conspicuous lure structure, which was similar to his other lists
      that rarely induced false recall. 80 participants (age range 18-28 years, M
      age=21.5 yr.) were presented eight 10-item lists, composed of four lists from
      each list structure. Contrary to expectations, the Inconspicuous lure structure
      produced less false recall than the Conspicuous lure structure. Moreover, better
      recall of list items was found in the Inconspicuous lure structure. These results
      were discussed in terms of semantic encoding related to contextual organization
      of the lists' structure.

PMID- 15739836
TI  - Subself theory and reincarnation/possession.
AB  - A subself model of the mind is used to account for multiple personality,
      possession, the spirit controls of mediums, reincarnation, and the auditory
      hallucinations of schizophrenics, with suggestions for empirical research.

PMID- 15739837
TI  - Multimodal behavioral treatment of nonrepetitive, treatment-resistant nightmares:
      a case report.
AB  - A 23-yr.-old young woman presenting with a 17-yr. history of nightmares was
      treated with a variety of behavioral and self-regulatory techniques. The
      nightmares were unusual in that they did not have an obviously common theme as in
      most published reports, and, therefore, did not readily lend themselves to
      several frequently used techniques. Although previous treatment episodes had not
      affected the incidence of the nightmares, a combination of relaxation procedures,
      a mnemonic to increase lucid dreaming, and dream rehearsal upon waking from a
      nightmare resulted in a sharp decrease in the frequency of nightmares in four
      sessions. Further improvement was reported over the next nine months as
      additional techniques were introduced and other problems treated, and was
      maintained during a 9-mo. follow-up.

PMID- 15739838
TI  - Coincidence anticipation and dynamic visual acuity in young adolescents.
AB  - Research involving college-age students and women fast pitch softball players
      indicated that coincidence anticipation and dynamic visual acuity are different
      visual abilities. This study used an alternative procedure to measure dynamic
      visual acuity to re-examine their relationship. Coincidence anticipation and
      dynamic visual acuity were measured in 24 young adolescents (12 boys, 12 girls)
      11 to 14 years of age. During the dynamic visual acuity procedure, the subject
      tracked an object of a constant size while the researcher manipulated the
      object's velocity. Analysis indicated that they are different visual abilities.
      Findings indicated that the dynamic visual acuity of boys was significantly
      better than that of girls, and coincidence anticipation between boys and girls
      did not differ.

PMID- 15739839
TI  - Effects of viewing pleasant and unpleasant photographs on facial EMG asymmetry.
AB  - 40 subjects' facial electromyographic (EMG) activity at the corrugator and
      zygomatic muscle regions were recorded while they were viewing pleasant and
      unpleasant photographs. Analysis showed that the EMG activity at the left
      zygomatic muscle region generated the highest power, followed by the right
      zygomatic, left corrugator, and right corrugator muscle regions, while viewing
      pleasant photographs. The EMG activity at the left corrugator muscle region
      generated the highest power, followed by the right corrugator, left zygomatic,
      and right zygomatic muscle regions, while viewing unpleasant photographs. Further
      statistical analysis indicated that the EMG activities at the left corrugator
      region generated significantly higher power than those at the right corrugator
      region while viewing unpleasant photographs. It was concluded that the intensity
      of facial EMG activity on the left side of the face was stronger than the right
      side of the face during the process of emotional expression.

PMID- 15739840
TI  - Participation motives in physical education: an expectancy-value approach.
AB  - This study applied an expectancy-value approach in examining participation
      motives of students in physical education. As predicted outcome expectancy, a
      variable formed by the combination of outcome value and outcome likelihood
      correlated significantly higher with motivational indices than these two factors.

PMID- 15739841
TI  - Repetitive motion in perception of tactile sensation in the fingers of string
      players.
AB  - Little is known about the mechanisms that underlie the pathophysiology involved
      in the development of cumulative trauma disorders. Musicians, specifically string
      players, may be a useful model to examine the cumulative effects of repetitive
      motion given the highly attended movements of their left hands and the
      stereotypical grasp of their right hands. Musculoskeletal disorders related to
      playing are experienced by 39% to 87% of musicians, making musicians a
      potentially good model for the study of factors involved in development of
      cumulative trauma disorders. Sensory thresholds for two-point discrimination and
      light touch were measured in all phalanges of each digit, of each hand.
      Comparisons were made within and between a control group of 10 nonmusicians who
      did not engage in repetitive motion and 10 healthy musicians who did. There were
      5 violinists, 2 violists, and 3 cellists. The Non-musician group perceived two
      points and light touch at significantly lower thresholds in the proximal
      phalanges of the left hand than the right hand. Significant differences were not
      present between right and left hands for the means of distal, middle, and
      proximal phalanges of the Musician group. This lack of significant difference may
      be due to higher sensory thresholds associated with repetitive use of the left
      hand of the musicians.

PMID- 15739842
TI  - Presentation of construction and improvement and modernization of the leg
      kinesthesiometer.
AB  - Construction and use of a mechanical kinesthesiometer for measuring magnitude and
      direction of errors at the knee for active and passive kinesthetic perception.

PMID- 15739843
TI  - Perceived enclosure of space, angle above observer, and distance to boundary.
AB  - Most previous research suggests that the horizontal size of a space has a strong
      effect on the perception of enclosure, but Hayward and Franklin reported in 1974
      that the main determinant of perceived enclosure was the ratio of boundary height
      (H) over the distance to boundary (D) rather than just the boundary height per se
      or distance per se. We attempted replication of that finding. Students (41 male,
      mean age=24.7 yr., SD=7.7) rated 16 images on a scale of open/enclosed. There was
      a strong effect on impressions of enclosure for angle above observer (r = .91),
      and this effect was larger than the effect of height (r = -.17), but there also
      was another strong effect for distance (r = -.68). Moreover, the effect of
      distance was dependent on angle above observer (r = -.52). Thus, partial
      replication was achieved, and a new relationship between the geometry of
      environments and perceived enclosure was identified.

PMID- 15739844
TI  - Self-generated elaboration and spacing effects on incidental memory.
AB  - The purpose of the present study was to investigate the effect of self-generated
      elaboration on incidental memory as a function of type of presentation (massed vs
      spacing). Subjects generated answers to "why" questions for target sentences in a
      self-generated elaboration condition. They then rated the appropriateness of the
      answers to the questions presented by the experimenter in an experimenter
      provided elaboration condition. This procedure was followed by free recall tests.
      The target sentences were presented twice, in either a massed presentation
      without intervening items between the first and the second presentation or spaced
      presentation in which 5 items appeared between the two presentations. The self
      generated elaboration effect, namely, higher recall, of self-generated
      elaboration over experimenter-provided elaboration, occurred with spaced but not
      with massed presentation. So, self-generated elaboration was facilitated in the
      spaced presentation because the time between the first and the second
      presentations led to richer encoding of each target.

PMID- 15739845
TI  - Clinical utility of color-form naming in Alzheimer's disease: preliminary
      evidence.
AB  - Performances on Alzheimer's Quick Test color-form naming and Mini-Mental State
      Examination were compared for 38 adults with Alzheimer's disease and 38 age- and
      sex-matched normal controls. Group means differed significantly and indicated
      longer naming times by adults with Alzheimer's disease. The specificity for AQT
      color-form naming was 97% and sensitivity 97%, i.e., 3% false negatives. The
      specificity for Mini-Mental State Examination was 100% and sensitivity 84%, i.e.,
      16% false negatives. These findings, while supporting AQT color-form naming as a
      screening test for reductions in cognitive speed associated with Alzheimer's
      disease, are preliminary given the relatively small sample.

PMID- 15739846
TI  - Primacy of B- and P-words: an exploratory study and a developmental hypothesis.
AB  - This study explored the utility of the bilabial stops [p and b] in comparison
      with other phonemes at the beginnings of words having a common visual reference.
      The initial hypothesis, based on the author's observations, was that it is easier
      to name common referents using words beginning with "b" rather than any other
      phoneme, whether vowel or consonant. This article places the hypothesis within
      the context of theory and research regarding phonological development. Secondly,
      a method is developed to explore further the generalization that common b-words
      have relatively high utility for visual referencing. Analysis indicates that
      words beginning with the bilabial stops [p and b] have the greatest utility. A
      developmental hypothesis is offered to help explain the findings.

PMID- 15739847
TI  - An analysis of home advantage in the English Football Premiership.
AB  - Home advantage has been examined across different sports. Pollard provided
      evidence of this phenomenon in association football (soccer). This present study
      further considers the prevalence in the English Football Premiership, a division
      created from the former Football Association First Division in 1992. Archived
      data were obtained for the First Division seasons 1984--5 to 1991--2 from the
      Football Statistics Archive and for the English Football Premiership (1992--3 to
      2002--3). Chi square analysis confirmed home advantage from season to season
      since 1984 (p<.05). Analysis of variance compared Pollard's findings and data for
      the English Football Premiership (1992--2003), as well as the intervening period
      (1984--92). Home advantage was significantly lower in these more recent periods.
      Possible factors contributing to the apparent decline in home advantage were
      highlighted.

PMID- 15739848
TI  - Variability in head movement during gait transitions.
AB  - Predictions from a model of coupled oscillators, which was based on stationary
      interlimb coordination, were examined in locomotor intralimb coordination. The
      present study measured head linear and angular accelerations and coordination
      relationships of the head and torso, e.g., using relative phase measures, during
      walking and running on a treadmill. Head linear acceleration increased from
      walking to running and decreased from running to walking, and head pitch/torso
      pitch relative phase decreased from walking to running and increased from running
      to walking. No other measures were significantly different for either walking or
      running (head angular acceleration, mean head vertical displacement/head pitch
      relative phase, SD head vertical displacement/head pitch, and SD head pitch/torso
      pitch). This information will aid further understanding of the many aspects
      involved in locomotor coordination.

PMID- 15739849
TI  - Discriminative power of basketball game-related statistics by level of
      competition and sex.
AB  - The purpose of this study was to identify the basketball game-related statistics
      that best discriminate performances by sex of players and level of competition.
      Archival data were obtained from the International Basketball Federation
      boxscores for all games during men's senior (n=62), men's junior (n=64), women's
      senior (n=62), and women's junior (n=42) World Championships. The game-related
      statistics gathered included 2- and 3-point field-goals (both successful and
      unsuccessful), free-throws (both successful and unsuccessful), defensive and
      offensive rebounds, blocks, assists, fouls, steals and turnovers. For the
      analysis only the close games were selected (N= 105, 1 to 12 points difference).
      Men's teams were discriminated from women's teams by their higher percentage of
      blocks and lower percentage of steals and unsuccessful 2-point field goals.
      Junior teams were discriminated from senior teams by their lower percentage of
      assists and higher percentage of turnovers. In the two-factor interaction, the
      teams were mainly discriminated by the game-related statistics identified for
      level of competition.

PMID- 15739850
TI  - Time required for motor activity in lucid dreams.
AB  - The present study investigated the relationship between the time required for
      specific tasks (counting and performing squats) in lucid dreams and in the waking
      state. Five proficient lucid dreamers (26-34 yr. old, M=29.8, SD=3.0; one woman
      and four men) participated. Analysis showed that the time needed for counting in
      a lucid dream is comparable to the time needed for counting in wakefulness, but
      motor activities required more time in lucid dreams than in the waking state.

PMID- 15739852
TI  - Validity and reliability of the Wood Motor Success Screening Tool in a special
      physical education learning laboratory.
AB  - The purpose of this study was to estimate the concurrent validity and test-retest
      reliability of the Wood Motor Success Screening Tool. Participants were 66
      children with learning and behavioral disabilities (44 boys and 22 girls; M of
      age= 7.6 yr.; SD of age= 1.8 yr.). The concurrent validity was checked using the
      Bruininks-Oseretsky Test of Motor Proficiency-Short Form as the criterion
      measure. A Pearson product-moment correlation of .84 (p< .01), a sensitivity
      index of .88, and a specificity index of .64 were found for estimating the
      concurrent validity. The test-retest reliability was checked using scores on the
      Wood Motor Success Screening Tool administered twice within a week. An intraclass
      correlation coefficient of .93 from the one-way analysis of variance was found
      for estimating the test-retest reliability. These results indicated that this
      test is valid and reliable for assessing young children.

PMID- 15739851
TI  - Variation in European suicide rates is better accounted for by latitude and
      longitude than by national percentage of Finno-Ugrians and Type O blood: a
      rebuttal of Lester and Kondrichin (2004).
AB  - The variation in contemporary suicide rates for men and women across 20 European
      nations is, in terms of shared variance, better accounted for by latitude and
      longitude than by national percentage of Finno-Ugrians and Type O blood, thus
      supporting the conclusion of Voracek, et al. in 2003 and refuting the supposition
      of Lester and Kondrichin of 2004. Discussion focuses on possible bases of this
      finding and on research problems pertaining to relations between suicide and
      blood type.

PMID- 15739853
TI  - Sex and competitive status in ankle inversion-eversion range of motion of college
      students.
AB  - The effects of sex and competitive status (athlete vs nonathlete) on ankle
      inversion-eversion range of motion was investigated. 62 collegiate athletes and
      36 collegiate nonathletes, both male and female, were tested. Analysis of
      variance showed significant (p<.05) main effects for sex but not competitive
      status or sex x competitive status. These results imply that college age women
      have more ankle rotational range of motion than men and that collegiate athletes
      in a group of various sports do not differ in ankle range of motion when compared
      to college nonathletes. Power in this sample did not permit definitive
      assessment.

PMID- 15739854
TI  - Developmental transition from object-centered to viewer-centered information in
      young children's drawings.
AB  - This study examined the developmental transition from object-centered to viewer
      centered information in young children's drawings. 66 children, ages 4 to 6 years
      old, drew a miniature snowman as they saw it. The miniature snowman was presented
      to them with the head positioned to the (1) front, (2) back, (3) left, or (4)
      right. The face of the snowman was always down and concealed while the children
      were drawing. 4-yr.-olds more often made canonical drawings, 5-yr.-olds made
      conflicting drawings, and 6-yr.-olds made view-specific or vertical drawings.
      These findings suggested that the 4-yr.-olds drew an object using object-centered
      information, the 5-yr.-olds confused object- with viewer-centered information,
      and 6-yr.-olds represented an object by viewer-centered information.

PMID- 15739855
TI  - Cognitive facilitation associated with Chinese brush handwriting: the case of
      symmetric and asymmetric Chinese characters.
AB  - Chinese calligraphic handwriting involves a process of visual spatial structuring
      of the characters as well as the motor control of the brush to follow specific
      character configurations through a projection of the cognitive images of the
      character. Previous research has shown that Chinese calligraphic handwriting
      facilitates perceptual and cognitive abilities. Reading Chinese characters with
      geometric features also facilitates cognitive processing. This study investigated
      Chinese calligraphic handwriting effect on cognitive facilitation measured by
      responses to asymmetric and asymmetric Chinese characters. 11 participants
      performed Chinese calligraphic handwriting for 30 min. and had their reaction
      time and error rate taken before and after the writing session. The reaction time
      to asymmetric characters was significantly shortened after Chinese calligraphic
      handwriting. These results confirm the general Chinese calligraphic handwriting
      effect on cognitive facilitation, but the asymmetric characters seem to result in
      greater such effects than the symmetric characters.

PMID- 15739856
TI  - Elite athletes' sensitivity to context: the case of a change in scoring system in
      table tennis.
AB  - 3 elite table tennis players' streams of actions during international matches
      were compared under the old scoring system (3 winning sets of 21 points) and the
      new (4 winning sets of 11 points). The organization of actions changed under the
      new system, with the relative duration of exploration activity becoming shorter
      than that of execution activity. These results indicate that elite performance in
      table tennis is characterized by the athletes' close attunement to elements of
      context--in this case, the scoring system--for the organization of their actions.

PMID- 15739857
TI  - Outcome expectations that motivate physical activity among world senior games
      participants.
AB  - This study validates a questionnaire which examines the role of selected outcome
      expectations from physical activity on motivating regular physical activity among
      a group of older adults. Data were obtained from a cross-sectional survey of 675
      participants in the 2002 World Senior Games. Factor analysis identified four
      clusters among 14 outcome expectation items, which were labeled Recreation and
      Social, Physical Health, Mental Health, and Self-image. The percentage agreeing
      that the selected items motivated physical activity were calculated and ranked
      from 1 (high) to 14 (low). The average ranking in each of the four factors was
      4.7 for Recreation and Social, 5.8 for Physical Health, 10.5 for Self-image, and
      11.7 for Mental Health. The ranks of items did not significantly differ across
      categories of sex, age, marital status, education, smoking, alcohol drinking, and
      disease history. However, the ranking did significantly differ between
      individuals who considered themselves to be physically active versus sedentary.
      Physically active individuals were most likely to agree that recreational
      enjoyment or fun motivated physical activity, whereas sedentary individuals were
      most likely to agree that improving the quality of life motivated physical
      activity.

PMID- 15739858
TI  - Isometric strength and dynamic back extensor endurance are unrelated in children
      ages 6-10 years: a pilot study.
AB  - This study assessed the correlation between back extensor isometric force and
      dynamic endurance in 69 children 6-10 years of age. Subjects were positioned
      prone with legs and hips supported and restrained on two folded 6-in. mats. 42
      subjects (20 girls; 22 boys) performed three 5-sec. isometric back extension
      efforts against a calibrated dynamometer and peak force values were averaged. An
      additional 27 subjects (9 girls; 18 boys) also performed a dynamic (0 degrees -->
      45 degrees flexion-->0 degrees) back extension test at a frequency of 20 per
      minute, and the number of repetitions was recorded. Both tests were repeated at a
      1-wk. interval. Pearson correlations for the endurance, the isometric force test,
      and test-retest, and between the functional concentric endurance vs isometric
      force were .55, .79 (both p<.01), and .03, respectively. These tests have
      moderate to high reliability but they examine different aspects of back muscle
      fitness. They should not be used interchangeably to assess back extensor muscle
      fitness. Further investigation must determine whether different dynamic test
      frequencies and mat heights yield different results.

PMID- 15739859
TI  - Efficacy of a mail survey appeal for a dissertation.
AB  - Of all the determinants of mail survey response investigated, a dissertation as
      the purpose is one type of appeal not used in a covering letter. Two parallel
      field experiments involving populations of wholesale organizations (N=743 and
      509) are reported in which such an appeal was tested. Lack of statistically
      significant findings indicates use of this appeal did not enhance response rate
      or quality.

PMID- 15739860
TI  - New Jersey hospitals renew their identities; part of Meridian Health. Raising
      awareness of the advantages of a healthcare system.
AB  - Meridian Health, Wall, N.J., is a three-hospital system that also includes a
      network of partner companies. The objectives of this branding campaign were to
      create a better awareness of the benefits of academic medicine, to close the
      physician referral loop and to improve internal morale. The objectives were
      realized by emphasizing the teamwork of the system's doctors and showing their
      actual faces and voices.

PMID- 15739861
TI  - New Terrace Park hospital in Iowa makes Trinity a two-state system. Ad campaign
      makes it more inviting to 'cross over the bridge'.
AB  - Trinity Regional Health System, Rock Island, Ill., grew into a two-state system
      some years ago, but Iowa residents really became interested when Trinity opened
      its Terrace Park facility in Bettendorf, Iowa. A multimedia campaign included a
      preview package with a spa certificate for physicians.

PMID- 15739862
TI  - Rich anniversary book honors 'The city that doctors built'.
AB  - Medical City, Dallas, celebrated its 30th anniversary with a special edition of
      its internal publication. Called "The City That Doctors Built," the substantial
      book honors the physicians that people this unique specialty hospital.

PMID- 15739863
TI  - OHSU web site readers have access to distinctive information. How to e-mail a
      child in the hospital; where to find a midwife.
AB  - Oregon Health & Science University (OHSU), Portland, Ore., posts a web site which
      generously covers the various aspects of this complex organization. Visitors to
      www.osuhealth.com, can find a midwife, send an email to a child in the hospital,
      and learn about the benefits of living in Oregon.

PMID- 15739864
TI  - Press kit leads to wide, consistent coverage of Parma Hospital honor.
AB  - At Parma Community General Hospital, Parma, Ohio, a press kit was created to
      recognize the hospital's designation as Ohio's number one hospital for joint
      replacement surgery. If you're proud of your press kit, we hope you'll consider
      sending it to us for this new feature.

PMID- 15739866
TI  - Needed: a phenomenology of illness.

PMID- 15739865
TI  - Media Monday tip sheet builds Spartanburg's media relations.
AB  - Media Monday is published weekly and sent to area newsrooms by the Spartanburg
      Regional Healthcare System, Spartanburg, S.C. The news and feature tip sheet was
      started in 1998 in order to disperse a lot of information with a limited number
      of staff.

PMID- 15739867
TI  - Pastoral research: past, present, and future.
AB  - In healthcare environments of excellence, clinically trained chaplains are valued
      members of the medical treatment team. There are skills and values they hold in
      common with medicine and allied health disciplines: enhancing the health and well
      being of the patient as a unity of body, mind, and spirit within a unique family
      and cultural system. This article examines the past, present, and future of
      pastoral research, including the chaplain's moral imperative to examine practice
      and to share what is found.

PMID- 15739868
TI  - Chaplain, soldier, counselor, pilgrim.
AB  - The author offers examples of supervision drawing on object relations therapy and
      Christian faith, doctrine, and life, designed to facilitate theological
      integration of pastoral identity and clinical practice in the training of U.S.
      Army Family Life Chaplains. Therapeutic and supervisory relationships are
      conceived of as dia-Logos encounters requiring the same degree of ascetical
      sobriety, presence, and vulnerability as prayer and worship. Concepts of
      therapeutic aggression, functional atheism, and "not knowing" are linked with on
      going self-examination and repentance stimulated by empathic engagement of
      clients as primary ingredients for spiritual growth and effective pastoral
      counseling.

PMID- 15739869
TI  - The modern mystic: a spirituality for health care workers.
AB  - In this essay the author suggests that a deepening of one's spirituality may be
      the nurture that is required to remain fulfilled when working in the health care
      professions; and she illustrates this thesis by tracing a young chaplain's
      deepening spiritual journey in a Clinical Pastoral Education program. As the
      young aspiring chaplain attempts to minister to Joe, a dying farmer, he embarks
      on a path that leads to a religious experience. The essay concludes by listing
      eight criteria or guidelines that may help pastoral caregivers realize that they
      themselves may be nurtured by meeting the Holy in their caregiving acts.

PMID- 15739870
TI  - Challenges to preparing and conducting christian worship in nursing homes.
AB  - This essay explores and details the various challenges that are faced in the
      design of Christian worship within the nursing home environment. People in this
      setting have special needs-physical, mental, social, and spiritual. The physical
      plant itself demands special considerations when preparing for worship.
      Difficulties are defined and solutions presented for those who would provide
      intentional and accessible Christian worship that allows for action and response
      from the community in these settings. Sources include Christian liturgical
      reference materials and on-site interviews with chaplains and activity directors
      at three care facilities in southeast Michigan.

PMID- 15739871
TI  - How satisfied are patients with the ministry of chaplains?
AB  - The author describes the importance of chaplaincy departments conducting periodic
      patient satisfaction studies and provides quantitative results from 1440 patients
      discharged from one of 14 U.S. general hospitals. Patients expressed the most
      satisfaction in response to the item, "The chaplain seemed to be a person of
      spiritual sensitivity." The results also suggest the characteristics of patients
      who appear most responsive to this ministry.

PMID- 15739872
TI  - A review of research on chaplains and community-based clergy in the Journal of
      the American Medical Association, Lancet, and the New England Journal of
      Medicine: 1998-2000.
AB  - Based on the content analysis of quantitative research appearing in three medical
      journals, the authors conclude that, despite the shared ideal of providing
      spiritual care to patients on the part of physicians and chaplains, there is
      little attention given in these journals demonstrating and promoting this shared
      perspective. Suggestions for future research that would focus on this common
      medicine/religion interface and concern are noted.

PMID- 15739874
TI  - Something to say.

PMID- 15739873
TI  - Trinity, polyphony and pastoral relationships.
AB  - The author explores the Christian doctrine of the Trinity to shed light on the
      nature of the pastoral ministry. Using the trinitarian term, "polyphony" (David
      Cunningham) for this purpose, he explicates unity and difference as key
      polyphonic categories in the doctrine of the Trinity. The author suggests that
      the polyphonic notes sounded by pastoral caregivers are toughness and tenderness,
      woundedness and health, wisdom and folly, and communion, nearness and distance.

PMID- 15739875
TI  - For everything there is a season: a time to howl!

PMID- 15739876
TI  - Unexpected blessings: Sunday morning in a homeless shelter.

PMID- 15739877
TI  - My father's house.

PMID- 15739878
TI  - The gift of presence by the ocean of sorrow and suffering.

PMID- 15739879
TI  - Scaling walls with empty hands.

PMID- 15739880
TI  - Response to article not very "chaplainy," or "chaplainish" or even
      "chaplainlike.".

PMID- 15739881
TI  - Subcritical water and dynamic sonication-assisted solvent extraction of
      fluorescent whitening agents and azo dyes in paper samples.
AB  - Two low-volume solvent continuous extraction methods are applied to the
      extraction of paper matrices. In the methods reported here, a complex mixture of
      fluorescent whitening agents (FWAs) and azo dyes (AZOs) used in paper materials
      intended to come into contact with foodstuffs was extracted by using subcritical
      water extraction (SWE) and dynamic sonication-assisted solvent extraction
      (DSASE). Rationale for the work is based upon migration concerns of these groups
      of analytes from the packaging to the packaged items, thus compromising their
      subjective and/or objective quality. In SWE, sample was extracted in 21 min with
      0.5 mL of water, whereas the DSASE method required 11 min and used 7 mL of water.
      DSASE was further developed by incorporating an organic modifier in order to
      change water polarity, thus improving extraction of moderately polar analytes.
      This way, modified-DSASE used a total organic volume of 0.9 mL which represents a
      reduction of 200 times in organic solvent consumption (200 mL versus
      approximately 1.0 mL) and 11 times in extraction time (2h versus 11 min) compared
      to the existing methods. SWE was able to extract only 9 out of 12 test analytes
      with average recoveries between 10 and 25% whereas modified-DSASE succeed in
      extracting all the target analytes with an average recovery of 89%. Complete
      discussion and explanation concerning these differences are provided in the text.

PMID- 15739882
TI  - High speed gradient elution reversed-phase liquid chromatography.
AB  - A major disadvantage of gradient elution in terms of speed results from the need
      to adequately re-equilibrate the column. This work distinguishes two states of re
      equilibration: (1) run-to-run repeatability and (2) full equilibration. We find
      that excellent repeatability (+/-0.002 min in retention time) is achieved with at
      most 2 column volumes of re-equilibration whereas full equilibration can require
      considerably more than 20 column volumes. We have investigated the effects of
      adding ancillary solvents (e.g. n-propanol, n-butanol) to the eluent and changing
      the particle pore size, initial eluent composition and type, column temperature
      and flow rate on the speed of full equilibration. Full equilibration seems to be
      more thermodynamically limited than kinetically controlled. Also, we show that
      the main limitation to reducing the full equilibration time is related to
      instrument design issues; a novel approach to overcome these instrumental issues
      is described.

PMID- 15739883
TI  - An artificial protein L for the purification of immunoglobulins and fab fragments
      by affinity chromatography.
AB  - The development and characterization of an artificial protein L (PpL) for the
      affinity purification of antibodies is described. Ligand 8/7, which emerged as
      the lead from a de novo designed combinatorial library of ligands, inhibits the
      interaction of PpL with IgG and Fab by competitive ELISA and shows negligible
      binding to Fc. The ligand 8/7 adsorbent (Ka approximately 10(4) M(-1)) compared
      well with PpL in binding to immunoglobulins from different classes and sources
      and, in addition, bound to IgG1 with K and lambda isotypes (92% and 100% of
      loaded protein) and polyclonal IgG from sheep, cow, goat and chicken. These
      properties were also reflected in the efficient isolation of immunoglobulins from
      crude samples.

PMID- 15739884
TI  - Theory of chromatographic separation of linear and star-shaped binary block
      copolymers.
AB  - Equations for the distribution coefficient of heteroarm stars are derived by
      using a model of an ideal chain in a slit-like pore; these equations together
      with those previously reported for linear block-copolymers are applied to
      describe chromatography of such copolymers. According to the theory, the
      retention generally depends on molar mass, composition, and architecture
      (microstructure and topology) of copolymers, on pore size and on adsorption
      interaction of chain units A and B. Three special modes of chromatography are
      studied in detail. (i) If interactions for A and B are close to the critical
      point of adsorption (CPA), the retention practically does not depend on
      architecture, and high molar mass copolymers can be separated by composition.
      (ii) At SEC condition for B and strong adsorption for A, copolymers in principle
      can be separated by architecture; better separation is expected in wide pores.
      Retention of linear block-copolymers decreases with increasing of the number of
      blocks; for heteroarm stars the theory predicts retention decreasing as: AB >
      StarAAB > StarABB; StarAAAB > StarABBB > StarAABB; StarAAAAB > StarABBBB >
      StarAAABB > StarAABBB. (iii) At the CPA for B copolymers AB, BAB and heteroarm
      stars regardless molar mass of B, M(B), can be separated by M(A). The same is
      true for ABA and ABAB...A in narrow pores. While the retention of AB, BAB, Star
      AB...B and StarAAB...B is the same, copolymers AB, ABA and linear multiblock
      copolymers can be separated, as well as symmetric and very asymmetric triblock
      copolymers ABA.

PMID- 15739885
TI  - Isolation and purification of the bioactive carotenoid zeaxanthin from the
      microalga Microcystis aeruginosa by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography was successfully applied for the first
      time to the isolation and purification of the bioactive carotenoid zeaxanthin
      from the cyanobacterium Microcystis aeruginosa. The crude zeaxanthin was obtained
      by extraction with organic solvents after the microalgal sample had been
      saponified. Preparative high-speed counter-current chromatography with a two
      phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (8:2:7:3,
      v/v/v/v) was successfully performed yielding zeaxanthin at 96.2% purity from 150
      mg of the crude extract in a one-step separation. The recovery of zeaxanthin was
      91.4%. This was also the first report that zeaxanthin was successfully separated
      and purified from microalgae.

PMID- 15739886
TI  - Determination of limonoate and nomilinoate A-ring lactones in citrus juices by
      liquid chromatography-electrospray ionization mass spectrometry.
AB  - The development of delayed bitterness in citrus products is a major problem to
      citrus producers and juice processors worldwide. A rapid and sensitive liquid
      chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method has
      been developed to quantify the recognized precursors of limonoid derived delayed
      bitterness, limonoate and nomilinoate A-ring lactones, in a wide variety of
      citrus juices. The limonoid A-ring lactones were isolated by solid-phase
      extraction from juice samples, analyzed by negative ion LC-ESI-MS and quantified
      utilizing the standard addition method.

PMID- 15739887
TI  - Thermodynamic study of N-trifluoroacetyl-O-alkyl nipecotic acid ester enantiomers
      on diluted permethylated beta-cyclodextrin stationary phase.
AB  - Thermodynamic studies were performed on 12 pairs of N-trifluoroacetyl-O-alkyl
      nipecotic acid ester enantiomers on diluted permethylated beta-cyclodextrin
      stationary phase (CP Chirasil-Dex CB). The influence of ester alkyl group
      structure on interaction with permethylated beta-cyclodextrin (Me-CD) and
      enantioselectivity was studied. The types of alkyl groups studied included n
      alkyl (C1-C5) and groups containing branching at differing locations relative to
      the chiral center of the molecule. The results show that for a given molecular
      weight, the n-alkyl esters have stronger interactions with Me-CD than esters
      containing branched alkyl groups. However, although having weaker interactions
      with Me-CD, esters containing alpha-branched alkyl groups exhibit higher
      enantioselectivity than the corresponding n-alkyl or beta-branched isobutyl
      esters. From the retention data, thermodynamic parameters were estimated using
      the retention increment method and enthalpy-entropy compensation plots (ln R'
      versus deltaH) were constructed. The results suggest that ester enantiomers with
      branching at the alpha-carbon of the ester alkyl group have additional and/or
      different types of enantioselective interactions with Me-CD than the C1-C5 n
      alkyl esters or beta-branched isobutyl ester. In order to obtain a qualitative
      sense of the interaction with Me-CD, structures of the diastereomeric complexes
      formed between Me-CD and some of the ester enantiomers were modeled using
      simulated annealing molecular dynamics.

PMID- 15739888
TI  - Development of an improved analytical method for the determination of
      carcinogenic polycyclic aromatic hydrocarbons in transformer oil.
AB  - Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer
      oils and are essential in prolonging transformer in-service lifetime. Issues
      concerning PAH carcinogenicity demand methods that provide qualitative and
      quantitative information on the PAH composition of new and in-service oils to
      allow informed operational decisions to be made. However, current analytical
      methods focus on PAH fingerprinting, as opposed to quantitative analysis and are
      also cumbersome, relying on the use of large (>100 ml) volumes of organic
      solvents, some of which are hazardous. This paper reports a method for the
      improved quantification of carcinogenic PAHs in transformer oils that is both
      simple and repeatable. The method uses commercially available solid-phase
      extraction columns and millilitre volumes of relatively non-hazardous solvents.
      Extraction efficiencies of > or =74% were obtained for the Environmental
      Protection Agency priority PAHs. The method has potential for automation and high
      throughput analysis and thus is of interest to industries that use transformer
      oils.

PMID- 15739889
TI  - Separation of phytosterol oxidation products by combination of different polarity
      gas chromatography capillary columns.
AB  - The number of characterized phytosterol oxidation products (POPs) from both ring-
      and side-chain structures has increased during recent decades, resulting in
      difficulties in the separation of POPs on different gas chromatography (GC)
      capillary columns. The main objective of this study was to separate a mixture of
      29 purified and characterized oxidation products from sito-, campe- and
      stigmasterol using GC capillary columns with different polarity. For the first
      time in the area of POPs analysis, the separation efficiency of the combination
      of two capillary GC columns with different polarities was investigated. A non
      polar 5% phenyl coated (DB5-MS) and a mid-polar 35% phenyl coated (DB35-MS)
      column was combined with a pressfit connector. The main improvement was enhanced
      base line separation for many of the analyzed POPs, compared with the separations
      achieved using the individual columns. However, three pairs of POPs co-eluted: 24
      hydroxysitosterol/campesterol-5beta,6beta-epoxide, stigmasterol-5beta,6beta
      epoxide/campesterol-5alpha,6alpha-epoxide and stigmasterol-5alpha,6alpha
      epoxide/campestanetriol.

PMID- 15739890
TI  - Determination of chloro-s-triazines including didealkylatrazine using solid-phase
      extraction coupled with gas chromatography-mass spectrometry.
AB  - Chloro-s-triazines are a class of compounds comprising atrazine, simazine,
      propazine, cyanazine and their chlorinated metabolites. The US Environmental
      Protection Agency (EPA) has determined that selected chloro-s-triazines-
      atrazine, simazine, propazine, deethylatrazine, deisopropylatrazine, and
      didealkylatrazine--have a common mode of toxicity related to endocrine
      disruption. In this paper, a dual-resin solid-phase extraction (SPE) gas
      chromatography-mass spectrometry (GC-MS) method is reported that provides for
      each of these chloro-s-triazines including the polar metabolite,
      didealkylatrazine. The method utilizes deuterated internal standards for
      quantitation and terbuthylazine as a recovery standard. The limit-of-detection
      was 0.01 microg/L for simazine, deethylatrazine, deisopropylatrazine and
      didealkylatrazine, and 0.02 microg/L for atrazine and propazine in surface water.
      Mean recoveries for 0.5 and 3.0 microg/L spikes for atrazine, simazine,
      propazine, deethylatrazine, deisopropylatrazine and didealkylatrazine were 94,
      104, 103, 110, 108 and 102%, respectively, in surface water. The method was also
      validated by matrix spikes into fourteen different raw and treated natural
      surface waters. This method is useful for monitoring "total chloro-s-triazines"
      in both raw and treated drinking waters.

PMID- 15739891
TI  - Analytical study of Joule heating effects on electrokinetic transportation in
      capillary electrophoresis.
AB  - Electric fields are often used to transport fluids (by electroosmosis) and
      separate charged samples (by electrophoresis) in microfluidic devices. However,
      there exists inevitable Joule heating when electric currents are passing through
      electrolyte solutions. Joule heating not only increases the fluid temperature,
      but also produces temperature gradients in cross-stream and axial directions.
      These temperature effects make fluid properties non-uniform, and hence alter the
      applied electric potential field and the flow field. The mass species transport
      is also influenced. In this paper we develop an analytical model to study Joule
      heating effects on the transport of heat, electricity, momentum and mass species
      in capillary-based electrophoresis. Close-form formulae are derived for the
      temperature, applied electrical potential, velocity, and pressure fields at
      steady state, and the transient concentration field as well. Also available are
      the compact formulae for the electric current and the volume flow rate through
      the capillary. It is shown that, due to the thermal end effect, sharp temperature
      drops appear close to capillary ends, where sharp rises of electric field are
      required to meet the current continuity. In order to satisfy the mass continuity,
      pressure gradients have to be induced along the capillary. The resultant curved
      fluid velocity profile and the increase of molecular diffusion both contribute to
      the dispersion of samples. However, Joule heating effects enhance the sample
      transport velocity, reducing the analysis time in capillary electrophoretic
      separations.

PMID- 15739892
TI  - Profiling flavor compounds of potato crisps during storage using solid-phase
      microextraction.
AB  - Headspace solid-phase microextraction (HS-SPME) was studied as a solvent free
      alternative method for the extraction and characterisation of volatile compounds
      in stored potato crisps by capillary gas chromatography coupled with mass
      detection. Better results were obtained when extraction was carried out at 70
      degrees C using a divinylbenzene (DVB)-carboxen (CAR)-polydimethylsiloxane fiber.
      The fiber was exposed for 20 min (extraction time) to the sample headspace,
      immediately after an equilibrium time of 5 min (time needed to reach the
      equilibrium between sample and above headspace). A total of 31 compounds were
      identified in oxidised potato crisps and resulted mainly from the
      degradation/rearrangement of lipids and carbohydrates.

PMID- 15739893
TI  - Magnetic hydrophilic methacrylate-based polymer microspheres for genomic DNA
      isolation.
AB  - Carboxyl groups containing magnetic and non-magnetic microspheres were used in
      solid-phase reversible immobilization (SPRI) of genomic DNA. Magnetic non-porous
      poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate)--P(HEMA-co-EDMA),
      poly(glycidyl methacrylate)--PGMA and P(HEMA-co-GMA) microspheres with
      hydrophilic properties were prepared by dispersion copolymerization of the
      respective monomers in the presence of colloidal iron oxides. DNA from chicken
      erythrocytes and DNA isolated from bacterial cells of Bifidobacterium longum was
      used for testing of adsorption/desorption properties of magnetic microspheres.
      The occurrence of false negative results in polymerase chain reaction (PCR)
      caused by the presence of extracellular inhibitors in DNA samples has been solved
      using SPRI. The P(HEMA-co-EDMA) and P(HEMA-co-GMA) microspheres were used for
      isolation of DNA from different dairy products followed by PCR identification of
      Bifidobacterium strains.

PMID- 15739894
TI  - Stepwise gradient of buffer concentration for capillary electrochromatography of
      peptides on sulfonated naphthalimido-modified silyl silica gel.
AB  - The advantage of using a stepwise gradient of buffer concentration in CEC was
      demonstrated with the mixed-mode stationary phase, 3-(4-sulfo-1,8
      naphthalimido)propyl-modified silyl silica gel (SNAIP). Before the application of
      a stepwise gradient, the effect of buffer concentration on the separations of six
      peptides and tryptic digests was investigated. Bubble formation caused by Joule
      heating at currents up to 95 microA was successfully suppressed by using SNAIP
      column even without pressurization, which contributed to a stepwise gradient of
      buffer concentration. Utilizing the stepwise gradient improved and shortened the
      separation of six peptides as compared to the separation under an isocratic
      elution.

PMID- 15739895
TI  - Cancer chemotherapy-induced nausea and vomiting: role of mediators, development
      of drugs and treatment methods.
AB  - The development of serotonin 5-HT3 receptor antagonists dramatically improved the
      treatment of chemotherapy-induced nausea and vomiting. Ondansetron, a serotonin 5
      HT3 receptor antagonist in combination with dexamethasone is widely used to treat
      chemotherapy-induced nausea and vomiting. This treatment regimen is effective
      against acute nausea and vomiting, but fails to control delayed nausea and
      vomiting. Metoclopramide along with other antiemetics are used to treat delayed
      nausea and vomiting. The high doses of metoclopramide needed may produce extra
      pyramidal side effects. The recent developments of 5-HT3 and dopamine D2 dual
      receptor antagonists have been found to exhibit a broad spectrum of activity
      against peripherally and centrally acting stimuli, but are not much effective
      against delayed emesis associated with chemotherapy. In various animal models,
      neurokinin NK1 receptor antagonists showed promising results against acute and
      delayed emesis, but the clinical trials revealed that triple therapy (NK1
      receptor antagonist, 5-HT3 receptor antagonist and dexamethasone) is superior
      than standard therapy (5-HT3 receptor antagonist & dexamethasone) or NK1 receptor
      antagonist alone, in controlling acute as well as delayed nausea and vomiting.
      Ginger, which is used traditionally for controlling emesis induced by various
      stimuli, also showed good activity against chemotherapy-induced nausea and
      vomiting in animal models. Non-pharmacological methods such as acupressure and
      acustimulation are good adjunct methods in treating nausea and vomiting. Since
      many mediators are involved in emesis induced by chemotherapy, cocktail treatment
      is proven to be more efficacious than a single drug, but increases treatment
      costs. So there is a need of further research in this field to get economically
      useful methods for the treatment of acute and delayed chemotherapy-induced nausea
      and vomiting.

PMID- 15739896
TI  - Search for histamine H3 receptor antagonists with combined inhibitory potency at
      Ntau-methyltransferase: ether derivatives.
AB  - With the recent development of new hybrid compounds having histamine H3 receptor
      antagonist with combined histamine Ntau-methyltransferase (HMT) inhibitory
      potency an innovative approach was described in the research of novel lead
      compounds modulating histaminergic neurotransmission. Several compounds
      containing an ether moiety derived from the recently published 4-(3
      piperidinopropoxy)phenylaminoquinoline derivatives (like FUB 836), were
      synthesized in this study and tested for their affinity at cloned human histamine
      H3 (hH3) receptors and on the inhibition of rat HMT. Besides different
      heterocycles, e.g. nitro- or amino-substituted pyridines, quinolines,
      benzothiazole or pyrroline, three classes of compounds were produced:
      heteroaromatic 3-piperidinopropyl ethers, keto- or imino-substituted 4-(3
      piperidinopropyl)phenyl ethers and 4-(3-piperidinopropyl)phenyl ethers with
      substituted (alkyl)aminopyridines. Whereas the (3-piperidinopropoxy)heterocycles
      showed only moderate activities on both test models, the 4-(3
      piperidinopropoxy)phenyl derivatives were identified as potent histamine H3
      receptor ligands and/or HMT inhibitors. Ki values up to 0.42 nM were found for
      the affinity to the hH3 receptor. HMT inhibitory potency was identified with IC50
      values about 0.3 microM for the most potent compounds in this series. Comparison
      of the pyridine-containing derivatives to recently published quinoline analogues
      showed a decrease in potencies for the pyridines. The dual activity, H3 receptor
      affinity and HMT inhibition, was moderate to good. For all compounds affinities
      at hH3 receptors were higher than their inhibitory HMT potencies. The described
      new histamine H3 receptor antagonists with an ether moiety represent a further
      promising step in our investigations for a dual activity.

PMID- 15739897
TI  - Design, synthesis and pharmacological evaluation of some novel 2-(4-nitrophenyl)
      3-methylthio-3-(substituted)arylamino acrylamides as potential anti-inflammatory
      agents.
AB  - On the basis of structure based drug design we have designed a series of 2-(4
      nitrophenyl)-3-methylthio-3-(substituted)arylamino acrylamides as potential
      antiinflammatory agents. Good 3D similarity was observed between the designed
      molecule and rofecoxib (r.m.s.d. 0.161). The effect of opening the central ring
      and introducing a spacer (-NH-) between one of the aryl rings and the central
      ring of the basic structure of the COX-2 inhibitors was also studied. The
      designed molecules were synthesised by thiocarbomylation of the 4-nitro
      phenylacetamide with aryl isothiocyanates followed by subsequent methylation of
      the enethiolate salts. All compounds were screened for their antiinflammatory
      activity by the carrageenan induced rat paw edema method. Compounds 4 and 6
      exhibited potent antiinflammatory activity, which was found to be comparable with
      the standard drug, rofecoxib. Both the potent molecules were also screened for
      their ulcerogenic potential in Albino rats. A very low ulcer index was observed
      with both compounds, although higher than rofecoxib.

PMID- 15739898
TI  - Glyceride derivatives as potential prodrugs: synthesis, biological activity and
      kinetic studies of glyceride derivatives of mefenamic acid.
AB  - In order to reduce the gastrointestinal side effect, of mefenamic acid, its
      carboxylic group was condensed with the hydroxyl group of 1,2,3-trihydroxy
      propane 1,3-dipalmitate/stearate to give 3a and 3b. These compounds were
      evaluated for their gastric toxicity, anti-inflammatory activity by the
      carageenan induced paw oedema test and analgesic activity by the acetic acid
      induced writhing method. The release of mefenamic acid from the esters 3a and 3b
      was studied at pH 3, 4, 5 and 7.4 with direct analysis by reverse phase HPLC
      using acetonitrile:acetate buffer (0.1 M, pH 3.5): methanol (40:25:35) at 1
      mL/min. The prodrugs showed less hydrolysis at pH 5 compared to pH 7.4 indicating
      that the prodrugs do not dissociate at stomach pH but release mefenamic acid at
      pH 7.4 in adequate amounts. The hydrolysis studies were also performed in rat
      plasma. A higher plasma concentration of mefenamic acid was observed in animals
      treated with 3a and 3b compared to the animals treated with the parent drug, and
      even after 8 h the concentration of mefenamic acid was 2 times higher. The peak
      plasma concentration of mefenamic acid in animals treated with mefenamic acid was
      attained in 1.5 h compared with 2 h in the case of prodrugs treated animals. The
      prodrugs showed less gastric ulceration compared to mefenamic acid at 100 mg/kg,
      a severity index of 1.10, 1.22 being observed with 3a, 3b and with mefenamic acid
      a severity index of 2.37 was observed. The prodrugs showed better anti
      inflammatory activity compared to the parent drug and analgesic activity
      comparable to the parent drug. These findings suggest that the prodrugs 3a and 3b
      synthesized might be used as biolabile prodrugs of mefenamic acid with increased
      bioavailability and less gastrointestinal side effects.

PMID- 15739899
TI  - A micellar electrokinetic capillary chromatography method for monitoring
      mycophenolic acid in serum of transplant recipients.
AB  - Mycophenolic acid (MPA), the active metabolite of the immunosuppressive agent
      mycophenolate mofetil (MMF), was for the first time quantified in the serum of
      transplant recipients using micellar electrokinetic capillary chromatography
      (MEKC). Sample preparation was carried out with solid phase extraction (SPE)
      using octadecyl-modified endcapped silica (C18 EC) as sorbent. Extremely varying
      recovery rates in preliminary experiments showed both the importance of pH
      monitoring during the single SPE steps and the necessity of an internal standard.
      MPA carboxy butyl ether (CBE), a specifically developed reference standard, was
      employed. Furthermore, optimisation of the MEKC parameters detection wavelength
      and injection time was of primary importance in order to enable the quantitation
      of therapeutic trough serum levels of MPA in the range lower than 5 microg x mL(
      1). Under optimised conditions, a limit of quantitation of 1.0 microg x mL(-1)
      was achieved allowing the determination of MPA in the serum of patients.

PMID- 15739900
TI  - Determination of rat urinary metabolites of icariin in vivo and estrogenic
      activities of its metabolites on MCF-7 cells.
AB  - To confirm that the estrogenic activity of icariin is based on the close
      relationship between the structures of its metabolites and the effects of their
      binding to target hormone receptors, the metabolism of icariin in rat urine was
      analyzed in vivo, and the estrogenic activity of its metabolites was measured in
      cultured MCF-7 human breast cancer cells, respectively. By CZE analysis, peaks
      corresponding to the relative positions of desmethylicaritin and icaritin were
      observed in the urine sample. Structural analysis following LC-ESI-MS revealed
      molecular ions [M-H]- of 512.8, 353.3, and 367.0 for metabolites consistent with
      those of icariside II, desmethylicaritin, and icaritin. Icariin, icaritin, and
      desmethylicaritin were analyzed for their estrogenicity using MCF7-cell
      proliferation (E-screen test). MCF-7 cells were cultured in an estradiol free
      medium and then exposed to 10(-8) to 10(-5) mol/L icariin and its metabolites,
      icaritin and desmethylicaritin, for 6 days. Icaritin and desmethylicaritin
      significantly increased cell proliferation, and the cell number increased from
      1.61 to 4.14 fold compared with the untreated control, but the parent compound
      icariin failed to exhibit this effect. These results indicate that icariin is
      converted to icariside II, desmethylicaritin, and icaritin in vivo, and that the
      latter two act as a weak xenoestrogen on MCF-7 cells.

PMID- 15739901
TI  - Quantification of omeprazole degradation by enteric coating polymers: an UV-VIS
      spectroscopy study.
AB  - The aim of this study was to investigate the degradation of the acid-labile
      proton-pump-inhibitor omeprazole in organic polymer solutions and aqueous
      dispersions of enteric coating polymers by UV spectroscopy. Furthermore, data
      were compared with those obtained in a previous HPLC study. For comparative
      purposes the cationic Eudragit RS 100 and the monomeric acid acetic acid were
      included in this study. The discolorations of degraded omeprazole solutions were
      analysed by VIS spectroscopy. UV-VIS spectra were recorded after preparation of
      the solutions and after 180 min of storage. The change of absorption was
      calculated as the difference of the absorption values at 305 nm. Degradation of
      omeprazole depends on the amount of acidic groups in the polymer structure. This
      decomposition manifests itself in a shifting of the absorption maximum to lower
      wavelengths and a decrease of absorption intensity. UV-VIS spectroscopy was used
      to determine the extent of degradation induced by enteric polymers. A good
      correlation of these results with previous HPLC data was found when excluding UV
      absorbing polymers. Nevertheless, values obtained by UV-VIS spectroscopy were
      always lower than those obtained by HPLC. For evaluation of the discoloration of
      degraded omeprazole solutions, VIS spectroscopy is a simple and fast method.

PMID- 15739902
TI  - Chitosan hydrochloride based microspheres of albendazole for colonic drug
      delivery.
AB  - Microspheres of chitosan hydrochloride (CH) were prepared in order to deliver
      albendazole specifically into the colon. Microspheres were prepared by an
      emulsion method using different ratios of drug and CH (1:1 to 1:5), agitation
      speeds (500 to 1500 rpm) and concentrations of glutaraldehyde in toluene as the
      cross-linking agent (0.25 to 1.0% w/v). The effect of polymer concentration,
      stirring rate and concentration of cross-linking agent on the particle size and
      drug loading was studied. With an increase in CH concentration, the average
      particle size was increased. Increased agitation speed reduced the size of the
      microspheres but higher agitation speed resulted in irregularly shaped
      microspheres. Increasing the concentration of cross-linking agent produced more
      regularly shaped microspheres of smaller size. The drug loading was highest at a
      drug: CH ratio of 1:3, stirring speed 1000 rpm and 0.75% w/v concentration of
      cross-linking agent. The effect of CH concentration on in vitro drug release from
      the microspheres was evaluated in simulated g.i.t fluids. A comparative in vitro
      drug release study of the optimized formulation was carried out in simulated
      colonic fluid, with and without 2% rat caecal content. The drug release in 24 h
      was 48.9% in colonic fluid without rat caecal content, and 76.5% in colonic fluid
      with rat caecal contents.

PMID- 15739903
TI  - Effects of N-alkyl-N,N-dimethylamine-N-oxides on the activity of purified
      sarcoplasmic reticulum Ca(2+)-transporting ATPase.
AB  - N-alkyl-N,N-dimethylamine-N-oxides (CnNO, n = 10-20 is the number of alkyl carbon
      atoms) stimulate the skeletal sarcoplasmic reticulum (SR) Ca(2+)-transporting
      ATPase activity at low concentrations and inhibit it at high concentrations. The
      minimum concentration (cmin), at which CnNO inhibits the ATPase, continuously
      decreases up to n = 16-18 and then increases. The values of Cmin are smaller than
      the CnNO critical micelle concentration (cmc) for C10NO-C14NO homologs, but
      larger than cmc for C18NO-C20NO homologs. The ATPase inhibition is caused by the
      CnNO-induced lipid bilayer structural perturbation in the ATPase annular region,
      modulated by the partition equilibria of the CnNO molecules between the bilayer
      and aqueous phase for short alkyl chain (n = 10-16) CnNO homologs, and between
      the bilayer, micelles and aqueous phase for long alkyl chain (n = 18-20) CnNO
      homologs.

PMID- 15739904
TI  - Hepatoprotective effect of isonicotinoylhydrazone SH7 against chronic isoniazid
      toxicity.
AB  - This study was carried out to investigate whether 3,5-dichloro-salicylaldehyde
      isonicotinoyl hydrazone (SH7), an analogue of the antituberculosis drug isoniazid
      (INH), recently synthesized in our laboratory, could prevent isoniazid-induced
      liver damage. Forty-two white healthy mice were treated, once daily for 30 days,
      with solutions of INH, SH7 and combinations of them at doses of 7.5 mg/kg p.o.
      and 15 mg/kg p.o. At the end of this period, livers were harvested for
      histopathological analysis. The levels of lipid peroxidation products (MDA) and
      the activities of antioxidant defense enzymes, superoxide dismutase (SOD) and
      catalase (CAT), were also measured in the liver homogenates. Treatments with
      combinations of INH and SH7 decreased the levels of MDA, normalized the
      previously depressed levels of SOD and CAT and prevented isoniazid-induced liver
      damages. A previously demonstrated tuberculostatic and superoxide scavenger
      activity (SSA) of the isonicotinoylhydrazone SH7 and results from the present
      study thus set out a proposal for a new isoniazid/SH7 combination therapy
      designed to provide hepatoprotection.

PMID- 15739905
TI  - A study on alpha-adrenoceptor mediated contractile responses of high fat diet fed
      rat thoracic aorta.
AB  - Feeding rats with high fat diet (HFD) leads to the various conditions of syndrome
      X. These are associated with hypertension through a variety of mechanisms.
      Vascular abnormalities probably contribute to the etiology of many diabetic
      complications. There is an increase in maximal responses to various agonists with
      blood vessels of streptozotocin induced diabetic animals. The purpose of this
      study was to evaluate the development in HFD fed rats for altered biochemical
      parameters, to assess the vascular responses to phenylephrine (PE), to estimate
      the KA values and to observe the receptor occupancy. Body weights, plasma
      triglycerides, cholesterol, and glucose levels were measured every week in male
      Sprague-Dawley rats. Glucose tolerance test was performed after 4 weeks of
      feeding. At the end of the fourth week of feeding, concentration-response curves
      of PE were recorded. Altered KA values of PE (NPD fed rats 2.0 +/- 0.4 microM and
      HFD fed rats 0.3 +/- 0.1 microM) and receptor occupancy response (NPD fed rats
      92.1 +/- 1.7% and HFD fed rats 77.5 +/- 5.6%) strongly suggest that hypertension
      in HFD fed rats is associated with altered alpha-adrenoceptor function.

PMID- 15739906
TI  - Effect of an aqueous distillate of Origanum onites L. on isolated rat fundus,
      duodenum and ileum: evidence for the role of oxygenated monoterpenes.
AB  - The aqueous distillate of Origanum onites L. (Labiatae) was reported to have
      various ethnomedical uses including effects on the gastrointestinal tract. The
      effects of three different doses (0.1, 0.2 and 0.4 mL) of the aqueous distillate
      of Origanum onites on isolated rat fundus, duodenum and ileum against
      acetylcholine induced contractions were investigated in this study. The aqueous
      distillate inhibited contractions in a dose dependent manner. Inhibitions were
      lowest on fundus. Carvacrol, being the major compound of the test substance, did
      not inhibit acetylcholine induced contractions of the isolated rat fundus,
      indicating the presence of other active principles including menthane diols. As
      being one of the first pharmacological studies on aqueous distillates, a possible
      pharmacological activity of cis-p-menth-4-ene-1,2-diol and 3,7-dimethyl-1-octen
      3,7-diol is proposed in this study.

PMID- 15739907
TI  - Effect of an aqueous extract of Scoparia dulcis on plasma and tissue
      glycoproteins in streptozotocin induced diabetic rats.
AB  - The influence of Scoparia dulcis, a traditionally used plant for the treatment of
      diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement
      in glycoprotein levels. Diabetes was induced in male Wistar rats by a single
      intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia
      dulcis plant was administered orally for 6 weeks. The effect of the Scoparia
      dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins
      studied was in comparison to glibenclamide. The levels of blood glucose and
      plasma glycoproteins were increased significantly whereas the level of plasma
      insulin was significantly decreased in diabetic rats. There was a significant
      decrease in the level of sialic acid and elevated levels of hexose, hexosamine
      and fucose in the liver and kidney of streptozotocin diabetic rats. Oral
      administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to
      decreased levels of blood glucose and plasma glycoproteins. The levels of plasma
      insulin and tissue sialic acid were increased whereas the levels of tissue
      hexose, hexosamine and fucose were near normal. The present study indicates that
      Scoparia dulcis possesses a significant beneficial effect on glycoproteins in
      addition to its antidiabetic effect.

PMID- 15739908
TI  - Three new polymeric isopropenyl benzofurans from Ligularia stenocephala.
AB  - Three new polymeric isopropenyl benzofurans, 4-methyl-2,4-bis(5,6-dimethoxy-2
      benzofuranyl)-1-pentene, stenocephalin A (1), 4,6-dimethyl-2,4,6-tri(5,6
      dimethoxy-2-benzofuranyl)-1-heptene, stenocephalin B (2) and 4,6,8-trimethyl
      2,4,6,8-tetra(5,6-dimethoxy-2-benzofuranyl)-1-nonene, stenocephalin C (3),
      together with seven known compounds (4-10) were isolated from the roots of
      Ligularia stenocephala. The structures of the new compounds were elucidated on
      the basis of spectral evidence, especially on 2D NMR. In addition, the cytotoxic
      activity and the anti-bacterial activity of compounds 2, 3, 5 and 6 were tested.

PMID- 15739909
TI  - The faculty perspective. The clinical long-term success of ceramic restorations-
      Part II: posterior full-coverage crowns.
AB  - The few clinical long-term studies published on all-ceramic posterior crowns
      indicate a favorable trend. In light of the well-documented longevity of
      conventional PFM crowns, however, more randomized controlled clinical long-term
      trials are necessary for one to recommend any technique or material over another.

PMID- 15739910
TI  - Current trends in implantology: part II--treatment planning, aesthetic
      considerations, and tissue regeneration.
AB  - In implant dentistry, bone loss is attributed to numerous factors that often
      include infection or trauma. Various surgical techniques and implant components
      have been developed to enable more effective management of such deficiencies.
      While the first installment of this article discussed the role of biological
      response and implant stability in implant therapy, this portion focuses on
      decision-making factors related to the number of implants, grafting materials,
      and achieving aesthetics with implant restorations. LEARNING OBJECTIVES: This
      article discusses factors that influence the outcome of implant restorations.
      Upon reading this article, the reader should: Be able to identify these factors
      and their effects. Be aware of the current trends in implant dentistry.

PMID- 15739911
TI  - Selecting a luting cement: part I.

PMID- 15739913
TI  - Tooth fragment reattachment: current treatment concepts.

PMID- 15739912
TI  - Rehabilitation of the edentulous mandible with a fixed implant-supported
      prosthesis.
AB  - Implant rehabilitation of an edentulous mandible presents significant
      improvements over conventional complete denture therapy with regard to patient
      satisfaction, and it can improve a patient's quality of life. Several implant
      prosthetic designs have been developed and successfully utilized in clinical
      practices. The goal of this article is to describe the prosthetic design and
      technical steps in the fabrication of a fixed implant-supported mandibular
      prosthesis. A technique is described in which the positioning of appropriately
      selected abutments is completed in a predictable manner. LEARNING OBJECTIVES:
      This article discusses the prosthetic designs and technical steps in fabricating
      a fixed implant-supported mandibular prosthesis. Upon reading this article, the
      reader should: Understand the prosthetic design for the treatment of an
      edentulous mandible. Recognize the significance of the technical steps in this
      rehabilitation process.

PMID- 15739914
TI  - Posterior direct restorations: innovative materials and procedures for aesthetic
      success.

PMID- 15739915
TI  - Laser periodontal treatment and surgical procedures: part I.

PMID- 15739916
TI  - Scanning and presenting slides: part I.

PMID- 15739917
TI  - Clinical protocol for an overdenture bar prosthesis fabricated with CAD/CAM
      technology.

PMID- 15739918
TI  - Impression-making protocol for the single-unit anterior implant restoration.

PMID- 15739919
TI  - Dental implants versus conventional tooth replacement.

PMID- 15739920
TI  - The pre-etch technique for achieving enamel bond strength with self-etching
      systems.

PMID- 15739921
TI  - Aesthetic crown lengthening: classification, biologic rationale, and treatment
      planning considerations.
AB  - The rationale for crown lengthening procedures has progressively become more
      aesthetic-driven due to the increasing popularity of smile enhancement therapy.
      Although the biologic requirements are similar to the functionally oriented
      exposure of sound tooth structure, aesthetic expectations require an increased
      emphasis on the appropriate diagnosis of the hard and soft tissue relationships,
      as well as the definitive restorative parameters to be achieved. The development
      of a clinically relevant aesthetic blueprint and attendant surgical guide is of
      paramount importance for the achievement of successful outcomes. LEARNING
      OBJECTIVES: This article provides a classification system that clinicians can use
      when treatment planning for aesthetic crown lengthening. Upon reading this
      article, the reader should have: A clear understanding of the involved biological
      structures. Didactic instruction on the classification and treatment planning for
      aesthetic crown lengthening procedures.

PMID- 15739922
TI  - Observations of an oncology social worker and mother about nurse and physician
      interaction.

PMID- 15739923
TI  - From "building" to "cultivating": changing the way we educate doctors and nurses
      in the 21st century.

PMID- 15739924
TI  - Enhancing and enriching the nurse-physician relationship.

PMID- 15739925
TI  - Continuing education for nurses: a problem-oriented system.

PMID- 15739926
TI  - Lingual thyroid gland--a case report and discussion.

PMID- 15739927
TI  - Mississippi Board of Medical Licensure: annual report.

PMID- 15739928
TI  - Medicaid crisis.

PMID- 15739929
TI  - Out with the old.

PMID- 15739930
TI  - Thoughts of a medical student on Mississippi Medicaid reform: is the present
      system taking care of the deserving poor?

PMID- 15739931
TI  - State leaders must acknowledge the "elephant in the room" to improve state's
      physician numbers.

PMID- 15739932
TI  - Flu update.

PMID- 15739933
TI  - Made in Canada? In search of a national research identity.

PMID- 15739934
TI  - Advancing nursing scholarship in diversity: complexity and equity.

PMID- 15739935
TI  - The conundrums of binary categories: critical inquiry through the lens of
      postcolonial feminist humanism.

PMID- 15739936
TI  - Connecting to nativeness: the influence of women's American Indian identity on
      their health-care decisions.
AB  - American Indian women experience health inequities within the physical, mental,
      and spiritual realms. Although the purpose of this study was to examine
      mammography decision-making processes among Native women in the northeastern
      United States, the role of Native identity in health-care decision-making in
      general was identified as significant and is therefore being reported
      independently. The findings of a grounded theory study with 20 American Indian
      women formed the basis for an examination of the complexities surrounding
      identity and health-care decision-making. The theme of Connecting to Nativeness
      reflects the individual and communal influences of Native identity on women's
      health and health-care decisions. Implications for researchers and clinicians,
      including the relationship between historical events and current constructions of
      identity, the fluid nature of identity, and the impact of racism on health-care
      decisions, are addressed.

PMID- 15739937
TI  - An exploration of the relationships between health promotion practices, health
      work, and felt stigma in families headed by adolescent mothers.
AB  - The purpose of this study was to examine the relationship between stigma and
      health promotion in families with preschool children headed by adolescent
      mothers, by: (a) testing hypotheses derived from the Developmental Model of
      Health and Nursing, and (b) descriptively exploring the experience of stigma in a
      community sample of 63 adolescent mothers in southwestern Ontario, Canada. The
      mothers verbally responded to established measures of felt stigma, family health
      work, healthy lifestyle practices, and a demographic questionnaire during a
      structured interview. Then their experiences of stigma were explored during a
      brief dialogic interview. Consistent with the theory, a moderate positive
      relationship was observed between family health work and mothers' healthy
      lifestyle (r = .52, p < .001). Felt stigma was not related to either health work
      or global healthy lifestyle. Stigma did not appear to affect family health
      promotion efforts directly but influenced other aspects of the participants'
      lives in both positive and negative ways. Implications for practice and future
      research are identified.

PMID- 15739938
TI  - Post-migration changes in gender relations among Ethiopian couples living in
      Canada.
AB  - The Ethiopian community ofToronto, Canada, has identified the prevention of
      marital conflict and partner abuse as a priority issue. Previous research and
      community discussions suggested that changes in gender relations following
      migration contribute to both marital conflict and partner abuse. The objective of
      this community-based pilot study was to explore post-migration changes in gender
      relations among Ethiopian couples in order to inform the development of violence
      prevention strategies. Qualitative research methods and analyses were used. In
      depth interviews and focus-group discussions were conducted with 8 couples who
      had been married in Ethiopia and migrated to Toronto. The findings indicate
      changes in gender relations following migration as well as concordant and
      discordant patterns of change. Change was found to be associated with factors
      such as age, number of years married, experience in a third country, and gender
      role socialization. Implications for future research and nursing practice are
      discussed.

PMID- 15739939
TI  - Out of the multiple margins: older women managing their health care.
AB  - This feminist phenomenological study explores the meaning of older women's
      experiences as they negotiate health care. Several interviews with diverse groups
      of older women (immigrant, First Nations, and Japanese-Canadian women and those
      involved in community and social clubs) reveal that negotiating to have their
      health needs met was a challenging process requiring mutual support. Their health
      care experiences were influenced by issues surrounding access to services, power,
      and poverty. For many participants, the conversational interview format served to
      inspire consciousness-raising, activism, and reflection. The findings suggest
      that such reflection may help other women to understand the "multiple margins"
      (being older, being a woman, being a member of a visible minority) that constrain
      and challenge their access to health care.

PMID- 15739940
TI  - Aboriginal beliefs about organ donation: some Coast Salish viewpoints.
AB  - A large number of Aboriginal people await transplantation, and reluctance to
      donate organs has been noted among Aboriginal people. The purpose of this study
      was to explore the values and beliefs regarding organ donation of Coast Salish
      people living in British Columbia, Canada. Interviews were held with 14 people (8
      women and 6 men) ranging in age from 25 to 63 years. Contextual themes were: lack
      of trust, life in Aboriginal communities, and tension between contemporary and
      traditional perspectives. Themes pertaining to death and dying were: acceptance
      of fate, death routines/rituals, and body wholeness. Themes pertaining to organ
      donation were: "we don't talk about it," transfer of spirit, and helping others.
      There was considerable diversity in beliefs among participants, which suggests
      that the beliefs held by an individual Aboriginal person should not be assumed to
      reflect those of any specific Aboriginal community.

PMID- 15739941
TI  - An exploration of othering in forensic psychiatric and correctional nursing.
AB  - In forensic and correctional environments, it is not uncommon for nurses and
      other health-care practitioners to depersonalize their patients and clients
      through their use of language. For example, referring to patients as "inmates"
      "cons," "psychopaths," "schizophrenics," or "monsters" not only evokes
      stereotypical images, but, more importantly, casts the individual in the role of
      the other. Othering is generally viewed as a negative form of engagement, one
      that is contrary to ethical nursing practice. Through the exploration of
      relational and contextual factors contributing to this phenomenon, the author
      argues that othering is a contemporary ethical issue that requires ongoing
      dialogue within the forensic and correctional nursing communities.

PMID- 15739942
TI  - Spiritual caregiving at the juncture of religion, culture, and state.
AB  - In response to the increasing social diversity of health-care recipients, nurse
      scholars have turned their attention to developing theoretical foundations for
      culturally responsive and spiritually sensitive nursing practice. However,
      despite the potential overlap between these 2 areas, there has been little
      exploration of the intersections between culture and spirituality. The authors
      present the findings of an interpretive descriptive pilot study that examined the
      contexts of intercultural spiritual caregiving from the perspectives of nurses
      and chaplains. The findings point to the need for health-care professionals to
      cultivate an internal space in which to provide spiritual care and to seek
      spiritual points of connection amidst diverse faith and cultural traditions. The
      contexts of current practice environments, as well as the social setting of a
      pluralistic and secular state, shape the dynamics of spiritual caregiving. The
      findings invite postcolonial, critical analyses of contemporary conceptions of
      spirituality and spiritual caregiving, and call for a rethinking of the trend
      towards de-emphasizing creedal religions in the quest for a universal spiritual
      experience.

PMID- 15739944
TI  - Photovoice: picturing the health of Aboriginal women in a remote northern
      community.

PMID- 15739943
TI  - Homophobia and heterosexism in cancer care: the experiences of lesbians.
AB  - This participatory, qualitative study examines "what is lesbian" about lesbians'
      experiences of cancer and cancer care. Twenty-six lesbians were interviewed about
      their experiences of cancer diagnosis, treatment, and support, and their feelings
      and perceptions about shifts in identity, body, sexuality, and relationships.
      This paper highlights how homophobia and heterosexism, in contemporary nursing
      practice and as historical features of the health-care system, shape the
      experiences of lesbians with cancer. A minority of participants were targeted,
      denied standard care, or had aspects of their identity and social context
      relevant to cancer care dismissed. The majority commented on the lack of
      attention to lesbian realities in psychosocial support. A legacy of heterosexism
      appears to prompt strategic efforts to avoid homophobia and also appears to
      foster gratitude for equitable care. Nurse educators, practitioners, and policy
      makers have critical roles to play in the accessibility of cancer care.

PMID- 15739945
TI  - CHNET-Works! A networking infrastructure for community health nurse researchers
      and decision-makers.

PMID- 15739946
TI  - Avian influenza, Viet Nam--update.

PMID- 15739947
TI  - Progress towards poliomyelitis eradication--poliomyelitis outbreak in Sudan,
      2004.

PMID- 15739948
TI  - Dracunculiasis eradication status, 2004.

PMID- 15739949
TI  - Revisions to the Federal Sentencing Guidelines for organizational defendants
      regarding compliance and ethics programs.

PMID- 15739950
TI  - The prompt, the alert, and the legal record: documenting clinical decision
      support systems.

PMID- 15739951
TI  - What's your ICD-10 plan? Findings and recommendations from research on ICD-10
      implementation.
AB  - Whats your plan for implementing ICD-10? A new study asked this question to 500
      healthcare managers and executives. Here are the highlights, with recommendations
      from those who have been there.

PMID- 15739952
TI  - Taking the measure of measures. Quality data initiatives and the challenge of
      effective and efficient data.
AB  - Tracking case outcomes helps improve care and create efficiency. But without
      universal reporting standards, the workload for hospitals is heavy and the data
      lacks uniformity.

PMID- 15739953
TI  - Patient data to go. Germany's national smart card project.

PMID- 15739954
TI  - Project management 101: Skills for leading and working in teams, part 2.

PMID- 15739955
TI  - HIPAA: it's different for manufacturers.

PMID- 15739956
TI  - The PHR effect.

PMID- 15739957
TI  - Making amendments meaningful.

PMID- 15739958
TI  - Data linkage--ready or not, it's here, part 1.

PMID- 15739959
TI  - Practice brief. Understanding the EHR system functional model standard.

PMID- 15739960
TI  - The trouble with DRGs, part 1.

PMID- 15739961
TI  - Cervical dysplasia and CIN--what's the difference?

PMID- 15739962
TI  - The power of knowledge: QI manager uses data to drive performance.

PMID- 15739963
TI  - Introduction to the special section: The role of cognitive-behavioral
      interventions in couple and family therapy.
AB  - Marriage and family therapists' perspectives on cognitive-behavior family therapy
      (CBFT) have seen major changes over the years. The focus on cognitions and
      behaviors in treatment is now widely embraced by marriage and family therapists
      because of the effectiveness of the approach and its flexibility and integrative
      potential. This article provides an introduction to the special section and a
      brief history and overview of the application of CBFT to the field and some of
      the benefits it can provide to the growing and ever-challenging area of couples
      and family therapy.

PMID- 15739964
TI  - The restructuring of family schemas: a cognitive-behavior perspective.
AB  - Cognitive-behavior therapists define schemas as cognitive structures that
      organize thought and perception. Schemas are also viewed as having an integral
      influence on emotion and behavior In this article, I examine the role of schema
      in family conflict and the specific interventions used in restructuring them
      during the course of family therapy. Further discussion highlights the concepts
      of attributions, assumptions, and family standards, and the role they play in
      schemas, as well as the overall family dynamics. Finally, a series of steps are
      suggested for facilitating the process of schema analysis and thought
      restructuring during the process of family therapy.

PMID- 15739965
TI  - Observational coding of relationship-schematic processing.
AB  - In this article, we introduce the construct Relationship-Schematic Processing
      (RSP), which is defined as the degree to which individuals process information in
      terms of their romantic relationship. We also present an observational coding
      system that was developed to assess the behavioral manifestations of RSP. The
      coding system was applied to videotaped problem-solving interactions completed by
      55 maritally distressed couples. Findings indicated that wives engaged in more
      frequent and higher quality RSP than husbands did. Husbands reported greater
      relationship satisfaction when wives engaged in more frequent and higher quality
      RSP; wives reported greater satisfaction when husbands engaged in higher quality
      relationship processing. In addition, we assessed convergent validity with other
      measures of marital functioning.

PMID- 15739966
TI  - Parenting schemas and the process of change.
AB  - Parents' childrearing behaviors are guided by schemas of the caregiving role,
      their functioning in that role, what children need in general, and what their own
      children are like in particular. Sometimes, however, parenting schemas can be
      maladaptive because they are too rigid or simple, involve inappropriate content,
      or are dominated by negative affect. In this article, we describe parenting
      schemas and provide an overview of empirical work documenting the characteristics
      of maladaptive parenting schemas. We review how intervention practices common to
      multiple therapeutic approaches (cognitive-behavior therapy, family therapy,
      parent training, attachment-based interventions, and psychoanalytic parent-infant
      psychotherapy) attempt to modify schemas to promote more optimal functioning
      among parents. We highlight how research in cognitive science may explain, in
      part, treatment effectiveness.

PMID- 15739967
TI  - Relationship standards and marital satisfaction in Chinese and American couples.
AB  - Samples of urban community couples in Shanghai, China, and suburban U.S. couples
      were administered measures of relationship adjustment and personal standards
      regarding characteristics of couple relationships. There were few gender
      differences in adherence to relationship standards but many differences between
      Chinese and U.S. couples. Fewer cultural differences existed in degree of couple
      consensus on relationship standards, but both adherence to standards and couple
      consensus on standards were associated with partners' levels of marital
      adjustment. Implications of the findings for clinical assessment and intervention
      with distressed couples, in particular for Western therapists working with
      Chinese couples whose standards may conflict with goals and methods of couple
      therapy, are discussed.

PMID- 15739968
TI  - Integrating research and clinical training in marriage and family therapy
      training programs.
AB  - The future of the profession and practice of marriage and family therapy (MFT)
      rests with those who promote the integration of research and clinical practice.
      The Boulder scientist-practitioner model is useful in conceptualizing MFT
      training, but it is not the perfect solution. Four MFT programs (two master's and
      two doctoral) are featured in this article for their work in integrating research
      and practice. Helpful strategies presented include: Encouraging students to
      question the therapy process; integrating research in the curriculum and
      supervision; discussing the positives and negatives of empirically supported
      treatments; focusing on change; and developing creative classroom experiences to
      use within the scientist-practitioner model.

PMID- 15739969
TI  - Publication patterns of faculty in commision on accreditation for marriage and
      family therapy education programs.
AB  - Journal articles published by faculty in Commission on Accreditation for Marriage
      and Family Therapy Education (COAMFTE) programs from 1998 to 2002 were analyzed
      to determine patterns regarding the amount and type of research conducted by this
      group. Fifty-eight percent of the articles were identified as research. Slightly
      more than 10% of these dealt with clinical processes and outcomes. Forty percent
      of studies reported a specific source of funding. Twenty-nine percent of research
      articles used qualitative methods, with percentages rising over the course of
      time. Results suggest the average number of publications per faculty member was
      relatively low, particularly for senior faculty. Implications for these findings
      are discussed.

PMID- 15739970
TI  - Studying marriage and family therapists in the 21st century: methodological and
      technological issues.
AB  - In this article, I present data from two waves of research on demographic
      characteristics and practice patterns of marriage and family therapists (MFTs)
      conducted in 2000 and 2002. The research focuses on the methodological and
      technological issues in studying this population. Specifically, an online survey
      with MFTs obtained lower response rates and was therefore more expensive relative
      to phone and mail methods. Questions about evidence-based therapies (EBTs) were
      asked two different ways with significantly different results based on how the
      questions were phrased. A discussion of the relative advantages and disadvantages
      of using different survey methodologies and consideration of issues pertinent to
      studying EBTs are included.

PMID- 15739971
TI  - Aesthetic forms of data representation in qualitative family therapy research.
AB  - In this article we provide a rationale for using alternative, aesthetic methods
      of qualitative representation (e.g., creative writing, art, music, performance,
      poetry) in qualitative family therapy research. We also provide illustrative
      examples of methods that bring findings to life, and involve the audience in
      reflecting on their meaning. One problem with such forms of data representation
      has been that, until recently, there have not been standards with which to
      evaluate them. We summarize evolving standards and explain when the forms are
      appropriate and when they are not. We also address issues of legitimacy and
      conflicting standards held by others.

PMID- 15739973
TI  - The paths from research to improved health outcomes.

PMID- 15739972
TI  - Initial levels of differentiation and reduction in psychological symptoms for
      clients in marriage and family therapy.
AB  - Using Bowen Family Systems Theory as a theoretical underpinning, in this study,
      we investigated the hypothesis that clients with higher levels of differentiation
      would improve more quickly in therapy than clients with lower levels of
      differentiation. Hierarchical Linear Modeling was used to analyze the data over
      nine sessions of therapy in a sample from an on-campus training clinic. The
      results suggest that there was variation in the initial levels of psychological
      symptoms and that differentiation was a significant predictor of this variance.
      The results also suggest that although psychological symptoms decreased over the
      nine sessions of therapy, there was very little variance in this change. These
      results are discussed in relation to Bowen Theory. The difficulties of doing this
      type of research and the lessons learned from this project are also discussed.

PMID- 15739974
TI  - Review: vaginal signs and symptoms perform poorly in diagnosing vaginal
      candidiasis.

PMID- 15739975
TI  - From research evidence to context: the challenge of individualizing care.

PMID- 15739976
TI  - Atorvastatin reduced major cardiovascular disease events in type 2 diabetes
      mellitus.

PMID- 15739977
TI  - Review: low-dose but not high-dose corticosteroids reduced all-cause mortality in
      severe sepsis and septic shock.

PMID- 15739978
TI  - Review: glucocorticoids reduced mortality in sepsis in recent (post-1997) but not
      previous (pre-1989) trials, or all trials combined.

PMID- 15739979
TI  - Review: oral and intravenous antibiotics do not differ for effectiveness in
      febrile neutropenic patients with cancer.

PMID- 15739980
TI  - Caspofungin was noninferior to amphotericin B for invasive fungal infections in
      persistent fever and neutropenia and was better tolerated.

PMID- 15739982
TI  - Review: cardiac resynchronization therapy reduces mortality and hospitalization
      for heart failure.

PMID- 15739981
TI  - Peginterferon alpha-2a alone or combined with lamivudine increased response rates
      more than lamivudine alone.

PMID- 15739983
TI  - Review: beta-blockers reduce mortality and therapy withdrawal in heart failure
      but increase dizziness and bradycardia.

PMID- 15739984
TI  - Isosorbide dinitrate plus hydralazine was effective for advanced heart failure in
      black patients.

PMID- 15739985
TI  - Invasive strategy within 24 hours of thrombolysis reduced death, nonfatal
      reinfarction, and ischemia-induced revascularization in STEMI.

PMID- 15739986
TI  - An early invasive strategy improved long-term freedom from major adverse cardiac
      events in older patients with angina.

PMID- 15739987
TI  - Dalteparin reduced venous thromboembolic events without increased bleeding in
      acutely ill medical patients.

PMID- 15739988
TI  - Stenting was noninferior to endarterectomy in patients with severe carotid artery
      stenosis and coexisting conditions.

PMID- 15739989
TI  - Review: nonsteroidal antiinflammatory drugs provide better pain relief than do
      opioids for acute renal colic.

PMID- 15739990
TI  - Gly/Gly and Arg/Arg genotype responses to albuterol differed in mild asthma.

PMID- 15739991
TI  - Etidronate, calcium, or both did not reduce fracture rates in patients with
      asthma receiving glucocorticoid treatment.

PMID- 15739992
TI  - A 10-day regimen of levofloxacin was not needed in patients with uncomplicated
      cellulitis who had an acceptable 5-day response.

PMID- 15739993
TI  - Lumiracoxib reduced ulcer complications compared with ibuprofen and naproxen in
      osteoarthritis and did not increase cardiovascular outcomes.

PMID- 15739994
TI  - Review: estrogen improves symptoms of overactive bladder in postmenopausal women.

PMID- 15739995
TI  - Computed tomographic colonography without cathartic preparation performed well in
      detecting colorectal polyps.

PMID- 15739996
TI  - Reduced glomerular filtration rate was associated with increased death,
      cardiovascular events, and hospitalization.

PMID- 15739997
TI  - Renal impairment increased mortality and cardiovascular complications after
      myocardial infarction.

PMID- 15739998
TI  - Hemoglobin A1c levels were associated with increased cardiovascular disease and
      all-cause mortality in persons with and without diabetes.

PMID- 15739999
TI  - Rate control was more cost-effective than rhythm control in persistent atrial
      fibrillation.

PMID- 15740001
TI  - NMR signal analysis to attribute the components to the solid/liquid phases
      present in mixes and ice creams.
AB  - The NMR relaxation signals from complex products such as ice cream are hard to
      interpret because of the multiexponential behavior of the relaxation signal and
      the difficulty of attributing the NMR relaxation components to specific molecule
      fractions. An attribution of the NMR relaxation parameters is proposed, however,
      based on an approach that combines quantitative analysis of the spin-spin and
      spin-lattice relaxation times and the signal intensities with characterization of
      the ice cream components. We have been able to show that NMR can be used to
      describe the crystallized and liquid phases separately. The first component of
      the spin-spin and spin-lattice relaxation describes the behavior of the protons
      of the crystallized fat in the mix. The amount of fat crystals can then be
      estimated. In the case of ice cream, only the spin-lattice relaxation signal from
      the crystallized fraction is relevant. However, it enables the ice protons and
      the protons of the crystallized fat to be distinguished. The spin-lattice
      relaxation time can be used to describe the mobility of the protons in the
      different crystallized phases and also to quantify the amount of ice crystals and
      fat crystals in the ice cream. The NMR relaxation of the liquid phase of the mix
      has a biexponential behavior. A first component is attributable to the liquid
      fraction of the fat and to the sugars, while a second component is attributable
      to the aqueous phase. Overall, the study shows that despite the complexity of the
      NMR signal from ice cream, a number of relevant parameters can be extracted to
      study the influence of the formulation and of the process stages on the ice
      fraction, the crystallized fat fraction, and the liquid aqueous fraction.

PMID- 15740000
TI  - The application of biosensors to fresh produce and the wider food industry.
AB  - The inherent specificity, selectivity, and adaptability of biosensors make them
      ideal candidates for use throughout the food industry. Potential applications
      within the supply chain range from testing of foodstuffs for maximum pesticide
      residue verification through to the routine analysis of analyte(s)
      concentrations, such as, glucose, sucrose, alcohol, etc., which may be indicators
      of food quality/acceptability. Biosensor formats include simple "one-shot"
      disposable devices that can be used either in the field or integrated into more
      sophisticated laboratory instruments. Until now, the main impact of these devices
      has been in the medical diagnostics field. However, with ongoing technical
      development, the food industry will be one of the prime beneficiaries of
      biosensor technology in the future. This report assesses the current and future
      trends in the application of biosensors to fresh produce and the wider food
      industry, focusing on both potential and current target analytes that are
      fundamental to fresh produce quality, traceability, and safety.

PMID- 15740002
TI  - Electron spin resonance spin trapping for analysis of lipid oxidation in oils:
      inhibiting effect of the spin trap alpha-phenyl-N-tert-butylnitrone on lipid
      oxidation.
AB  - The electron spin resonance (ESR) spin trapping technique was investigated as an
      analytical approach to follow lipid oxidation of rapeseed oil, sunflower oil, and
      fish oil during storage at 40 degrees C. Unlike previous investigations, alpha
      phenyl-N-tert-butylnitrone (PBN), used as spin trap, was added to the fresh oils
      and formation of radicals was monitored during storage. Results were compared
      with the development in peroxide value (PV) and the thiobarbituric acid index
      (TBA). Increasing radical development was detected during the initial stages of
      oxidation, during which no significant changes in PV and TBA were observed.
      Evidence of spin adduct depletion was found during prolonged storage, suggesting
      that although spin trapping of radicals may be used to follow early events in
      lipid oxidation, it is not a suitable parameter for long periods of time.
      Addition of the spin trap after sequential samplings is recommended for getting
      an insight of oxidative changes during storage. Further, the influence of the
      spin trap (PBN) on lipid oxidation was studied in detail by application of PV and
      TBA and by following the depletion of naturally occurring tocopherol. PBN was
      found to possess a profound inhibiting effect on lipid oxidation. Such an effect
      was found to be dependent on the nature of the oil, and it was observed that the
      lower the oxidative stability, the larger the effect of PBN on lipid oxidation.
      This effect was interpreted in terms of the capability of PBN to react with
      peroxyl radicals, which in turn depends on the initial tocopherol content of the
      oils.

PMID- 15740003
TI  - Real-time polymerase chain reaction quantification of the transgenes for roundup
      ready corn and roundup ready soybean in soil samples.
AB  - A method for quantification of recombinant DNA for Roundup Ready (RR) corn and RR
      soybean in soil samples is described. Soil DNA from experimental field samples
      was extracted using a soil DNA extraction kit with a modified protocol. For the
      detection and quantification of recombinant DNA of RR corn and RR soybean, a
      molecular beacon and two pairs of specific primers were designed to
      differentially target recombinant DNA in these two genetically modified crops.
      Soil DNA extracts were spiked with RR corn or RR soybean DNA, and recombinant DNA
      was quantified using real-time PCR with a molecular beacon. As few as one copy of
      RR corn genome or one copy of RR soybean genome was detected in the soil DNA
      extract.

PMID- 15740004
TI  - Authentication of the botanical origin of honey by front-face fluorescence
      spectroscopy. A preliminary study.
AB  - The potential of front-face fluorescence spectroscopy for the authentication of
      unifloral and polyfloral honey types (n = 57 samples) previously classified using
      traditional methods such as chemical, pollen, and sensory analysis was evaluated.
      Emission spectra were recorded between 280 and 480 nm (excit: 250 nm), 305 and
      500 nm (excit: 290 nm), and 380 and 600 nm (excit: 373 nm) directly on honey
      samples. In addition, excitation spectra (290-440 nm) were recorded with the
      emission measured at 450 nm. A total of four different spectral data sets were
      considered for data analysis. After normalization of the spectra, chemometric
      evaluation of the spectral data was carried out using principal component
      analysis (PCA) and linear discriminant analysis (LDA). The rate of correct
      classification ranged from 36% to 100% by using single spectral data sets (250,
      290, 373, 450 nm) and from 73% to 100% by combining these four data sets. For
      alpine polyfloral honey and the unifloral varieties investigated (acacia, alpine
      rose, honeydew, chestnut, and rape), correct classification ranged from 96% to
      100%. This preliminary study indicates that front-face fluorescence spectroscopy
      is a promising technique for the authentication of the botanical origin of honey.
      It is nondestructive, rapid, easy to use, and inexpensive. The use of additional
      excitation wavelengths between 320 and 440 nm could increase the correct
      classification of the less characteristic fluorescent varieties.

PMID- 15740005
TI  - Immunosensor for rapid detection of gibberellin acid in the rice grain.
AB  - A rapid, selective, sensitive, accurate, and inexpensive immunosensor for
      gibberellin acid detection was designed by coupling immunoassay with the square
      wave anodic stripping voltammetry (SWASV) technique involving copper ion labeled
      antigen in the competitive immunoreaction. The response signal expressed as the
      percentage of current reduction CR % (y) is linearly related to the concentration
      of GA (x) in the 1 microg/mL to approximately 150 microg/mL range with a
      regression equation of the form y = 0.44x + 15.59 and a correlation coefficient
      of 0.99. The results of the immunosensor assay were compared with those obtained
      by HPLC and ELISA, which show a satisfactory agreement. The immunosensor was used
      to determine the GA content in the hybrid rice grain samples taken in the growing
      period.

PMID- 15740006
TI  - Nondestructive evaluation of anthocyanins in olive (Olea europaea) fruits by in
      situ chlorophyll fluorescence spectroscopy.
AB  - Anthocyanins (Anths) in olive (Olea europaea L.) fruits at different degrees of
      pigmentation were assessed nondestructively by measuring chlorophyll fluorescence
      (ChlF). The method is based on the comparison of the ChlF excitation spectra from
      olives with different pigmentation from green to green-red, reddish-purple, and
      purple. The logarithm of the ratio between the fluorescence excitation spectra
      (logFER) from two different colored zones gave the difference in the absorption
      spectrum between them. The absorbance spectrum derived from the logFER between a
      red olive and the same olive devoid of the skin showed the typical Anth green
      band (at 550 nm). It matched that recorded by microspectrophotometry on a single
      pulp cell and the in vitro absorbance spectrum of the olive skin extract. As
      expected, the in vivo Anths absorption maximum increased in intensity going from
      less to more mature olives and was higher in the sun-exposed olive side with
      respect to the sun-shaded side. Absolute quantitative nondestructive
      determination of Anths for each olive sample was obtained by the logFER
      calculated for two excitation wavelengths, 550 and 625 nm, of ChlF at 740 nm.
      Going from green to purple skin colors, the Log[ChlF(625)/ChlF(550)] was fairly
      well-correlated to the extract Anths concentration. Finally, the relationship
      between the Anths and the other main phenolics present in the olives analyzed by
      high-performance liquid chromatography was evaluated. The main result was a net
      increase of verbascoside with increasing Anths content. On the basis of our
      results, the development of a new rapid and noninvasive method for the monitoring
      of olive development and ripening can be envisaged.

PMID- 15740007
TI  - Development of a sensitive high-performance liquid chromatography-diode array
      detection assay for the detection and quantification of the beauveria metabolite
      oosporein from submerged culture broth and bio-control formulations.
AB  - A sensitive high-performance liquid chromatography-diode array detection (HPLC
      DAD) assay is described for the detection and quantification of the Beauveria
      metabolite oosporein from fungal culture broth and two biocontrol agent
      formulations. In all cases, analyte recovery was achieved with a Britton-Robinson
      buffer system at pH 5.5 diluted with methanol 3:7 (v/v) (BR5.5-MeOH). The HPLC
      DAD assay, using a binary solvent gradient with acidic modifiers and detecting
      the metabolite at 287 nm, showed linearity over 3 orders of magnitude and a limit
      of detection (LOD) of 6.0 +/- 2.3 microg of oosporein/L of BR5.5-MeOH. The
      oosporein content of the representative fungal culture broth samples and two
      Beauveria formulations (Melocont-Pilzgerste and Melocont-WP) was found to be
      504.7 +/-13.6 mg of oosporein/L of culture filtrate, 7.4 +/- 0.6 mg of
      oosporein/kg of Melocont-Pilzgerste, and 38.2 +/- 1.3 mg of oosporein/kg of
      Melocont-WP with recovery rates of 93 +/- 2, 99 +/- 8, and 92 +/- 3%,
      respectively.

PMID- 15740008
TI  - Rapid determination of polyphenols and vitamin C in plant-derived products.
AB  - Polyphenols, widely spread in our diet by the consumption of plant food products,
      are commonly determined using Folin-Ciocalteu reagent that interacts with other
      different reducing nonphenolic substances and leads to an overestimation of
      polyphenol content. In this paper we report an optimized Folin-Ciocalteu method
      to specifically determine the contents of total polyphenols and vitamin C. After
      the optimal conditions for the colorimetric assay were set, solid-phase
      extraction (Oasis HLB (hydrophilic-lipophilic balance)) was carried out to
      eliminate the water-soluble reducing interferences including vitamin C.
      Colorimetric correction was thus performed by subtracting interfering substances
      contained in the water washing extract from the raw extract. Moreover, vitamin C
      present in the water washing extract can be destroyed by heating and thus
      colorimetrically deduced. This procedure was set up with synthetic solutions and
      validated on different extracts from fruit products.

PMID- 15740009
TI  - Analysis of nitrogen fractions in silage by near-infrared spectroscopy.
AB  - Total nitrogen, soluble nitrogen (SN), nonprotein nitrogen (NPN), and acid
      detergent insoluble nitrogen (ADIN) were analyzed in grass silage by near
      infrared (NIR) spectroscopy. A set of 144 samples was used to calibrate the
      instrument by modified partial least-squares regression, and the following
      statistical results were achieved: standard error of calibration (SEC) = 0.449
      and square correlation coefficient (R (2)) = 0.98 for total nitrogen x 6.25, SEC
      = 0.425 and R (2) = 0.95 for SN x 6.25, SEC = 0.414 and R (2) = 0.94 for NPN x
      6.25, and SEC = 0.139 and R (2) = 0.84 for ADIN x 6.25. To validate the
      calibration performed, a set of 48 silage samples was used. Standard errors of
      prediction were 0.76, 0.64, 0.63, and 0.25 for total nitrogen, SN, NPN, and ADIN
      (all of them multiplied by 6.25), respectively, and R (2) for the regression of
      measurements by reference method versus NIR analysis were 0.94, 0.92, 0.90, and
      0.48 for total nitrogen, SN, NPN, and ADIN, respectively. To compare the results
      obtained by NIR spectroscopy with those obtained by the reference methods for
      total nitrogen, SN, and NPN of the validation set, linear regression and paired t
      tests were applied, and the results were not significantly different (p = 0.05).
      When mean square prediction error analysis was applied, it could be concluded
      that for total nitrogen, SN, and NPN, a robust calibration model was obtained and
      that the main error was unexplained error. Statistical data for ADIN were worse
      than those of the other parameters; as a result NIR spectroscopy is not an
      effective method for quantitative analyses of ADIN in silage; nevertheless, it
      may be an acceptable method for semiquantitative evaluation.

PMID- 15740010
TI  - LC/TIS-MS fingerprint profiling of Cimicifuga species and analysis of 23-Epi-26
      deoxyactein in Cimicifuga racemosa commercial products.
AB  - In this study, a liquid chromatography (LC)/turbo ion spray (TIS)-mass
      spectrometry (MS) method was developed to examine the chromatography or
      "fingerprint profile" of seven Cimicifuga herbs and six Cimicifuga racemosa
      (black cohosh) commercial products. Triterpene glycoside components were selected
      as chemical markers for analysis because they have appeared as a major compound
      group in Cimicifuga species. LC/MS chromatograms unveiled the patterns of C.
      racemosa, Cimicifuga dahurica, Cimicifuga foetida, Cimicifuga heracleifolia,
      Cimicifuga japonica, Cimicifuga acerina, and Cimicifuga simplex, which are very
      different from each other. 23-Epi-26-deoxyactein was found only in C. racemosa,
      C. dahurica, and C. foetida. A highly selective and sensitive LC/MS/MS method for
      quantitative analysis of 23-epi-26-deoxyactein with detection levels up to 2.5 ng
      in these samples was also developed and was applied to six commercial C. racemosa
      products. C. racemosa and its six commercial products contained about 6-15% of 23
      epi-26-deoxyactein in total triterpene glycosides. On the other hand, the
      estimated amount of total triterpene glycosides in other commercial products was
      either greater or lesser than what the manufacturers claimed. The technique and
      LC/MS profiles generated in this study provide a reliable and reproducible method
      that can be readily utilized for botanical identification of Cimicifuga plants,
      for examination and validation of its commercial products, and for "chemical"
      quality control in the manufacture of black cohosh products.

PMID- 15740011
TI  - Identification and quantification of polyphenolic compounds in Longan (Euphoria
      longana Lam.) fruit.
AB  - Regular consumption of fruit and vegetables is associated with a lower risk of
      some chronic diseases including various forms of cancer and cardiovascular
      diseases. The health-promoting potential of these foods may be due, in part, to
      the phytochemical bioactive compounds present in the plants. Fruit of Euphoria
      longana Lam. (longan) are consumed throughout Asia and are a major crop in
      Thailand. In the present study phytochemicals were extracted with 70% methanol
      from peel, pulp, and seed tissues of longan fruit, and the major components were
      identified as gallic acid, corilagin (an ellagitannin), and ellagic acid. A high
      through-put reversed phase HPLC method was developed to determine the content of
      these three compounds in different parts of the longan fruit and among different
      cultivars. The analyses showed that there was a large variation in the contents
      of gallic acid, corilagin, and ellagic acid in different plant tissues and
      cultivars. Seed contained the highest levels of the three phenolics, and pulp
      contained the lowest. Among commercial cultivars, Biewkiew and Edor contained the
      highest levels of gallic and ellagic acid while Srichompoo contained the highest
      content of corilagin. These three cultivars may be used in directed breeding and
      cultivation programs and to develop concentrated longan seed extracts to promote
      good health. Utilization of this byproduct material will support the use of
      thousands of tons of waste longan seeds after the production of canned longan
      pulp.

PMID- 15740012
TI  - Is there a better source of huperzine A than Huperzia serrata? Huperzine A
      content of Huperziaceae species in China.
AB  - A precise and selective reversed phase high-performance liquid chromatographic
      method was developed for quantifying huperzine A (HupA) in samples of the
      Huperziaceae in China. This method was used to quantify the levels of HupA in
      samples of Huperzia serrata collected from a single population at different times
      of the year, in different organs of the same H. serrata plant, and from different
      geographical locations of H. serrata plants in China. For different species of
      Huperziaceae, the highest content of HupA was found in Phlegmariurus carinatus.
      Members of the genus Phlegmariurus possessed higher levels of HupA than Huperzia
      species. H. serrata plants growing in humid forests contained significantly more
      HupA than plants growing in less humid environments. Finally, HupA content varied
      significantly by season, with the highest levels being found in mid fall and the
      lowest levels in early spring, suggesting that HupA is turned over in the plant.

PMID- 15740013
TI  - Contribution of chlorogenic acids to the iron-reducing activity of coffee
      beverages.
AB  - The iron-reducing activity of coffee beverages was determined by the ferric
      reducing antioxidant power (FRAP) assay. The influence on FRAP due to the degree
      of roasting (light, medium, and dark), species (Coffea arabica and Coffea
      robusta), and caffeine content (regular and decaffeinated) was investigated using
      ground and soluble coffee samples. The concentration of specific chlorogenic
      acids and caffeine in the beverages was determined by high-performance liquid
      chromatography and related to FRAP using Pearson correlation coefficients. All
      measurements were expressed per unit of soluble solids. Beverages prepared with
      ground coffee had, on average, 27% higher FRAP values than those prepared with
      soluble coffee (p < 0.05). In the former beverages, FRAP of C. robusta samples
      was significantly higher (on average, 50.3%) when compared to that of C. arabica
      samples, and FRAP values decreased with increasing degree of roasting (p < 0.05).
      A strong correlation (r > 0.91) was found between FRAP and the total content of
      chlorogenic acids, particularly that of the caffeoylquinic acid isomers. The iron
      reducing activity of coffee beverages was not influenced by caffeine.

PMID- 15740014
TI  - Unraveling the contribution of melanoidins to the antioxidant activity of coffee
      brews.
AB  - Instant coffees produced from the same green coffee beans were supplied from a
      company in different roasting degrees, light, medium, and dark. Melanoidins were
      obtained by ultrafiltration (10 kDa) and subsequent diafiltration. Pure
      melanoidins were isolated from melanoidins after overnight incubation in 2 M
      NaCl. The antioxidant activities of instant coffees, melanoidins, and pure
      melanoidins were tested using the conjugated diene formation from a 2,2'-azobis(2
      amidinopropane) dihydrochloride-induced linoleic acid oxidation in an aqueous
      system. No significant differences were found between melanoidins and pure
      melanoidins with different roasting degrees. Therefore, the contribution of the
      pure melanoidin fraction to the total antioxidant activity of melanoidins was
      significantly lower. More than 50% of the antioxidant activity of melanoidins is
      due to low molecular weight compounds linked non-covalently to the melanoidin
      skeleton. A new concept of the overall antioxidant properties of food melanoidins
      is described, where chelating ability toward low molecular weight antioxidant
      compounds is connected to the stabilization of these compounds involved in the
      shelf life of the product.

PMID- 15740015
TI  - Screening of chemical composition and antifungal and antioxidant activities of
      the essential oils from three Turkish artemisia species.
AB  - The compositions of essential oils isolated from the aerial parts of Artemisia
      absinthium, Artemisia santonicum, and Artemisia spicigera by hydrodistillation
      were analyzed by GC-MS, and a total of 204 components were identified. The major
      components of these essential oils were camphor (34.9-1.4%), 1,8-cineole (9.5
      1.5%), chamazulene (17.8-nd%), nuciferol propionate (5.1-nd%), nuciferol
      butanoate (8.2-nd%), caryophyllene oxide (4.3-1.7%), borneol (5.1-0.6%), alpha
      terpineol (4.1-1.6%), spathulenol (3.7-1.3%), cubenol (4.2-0.1%), beta-eudesmol
      (7.2-0.6%), and terpinen-4-ol (3.5-1.2%). The antifungal activities of these
      essential oils were tested against 11 plant fungi and were compared with that of
      a commercial antifungal reagent, benomyl. The results showed that all of the oils
      have potent inhibitory effects at very broad spectrum against all of the tested
      fungi. Pure camphor and 1,8-cineole, which are the major components of the oils,
      were also tested for antifungal activity against the same fungal species. Unlike
      essential oils, these pure compounds were able to show antifungal activity
      against only some of the fungal species. In addition, the antioxidant and DPPH
      radical scavenging activities of the essential oils, camphor, and 1,8-cineole
      were determined in vitro. All of the studied essential oils showed antioxidant
      activity, but camphor and 1,8-cineole did not.

PMID- 15740016
TI  - Sulforaphane, erucin, and iberin up-regulate thioredoxin reductase 1 expression
      in human MCF-7 cells.
AB  - Isothiocyanates (ITCs) found in cruciferous vegetables are potentially important
      anticarcinogenic phytochemicals for many types of cancers including breast
      cancer. In this study, we have shown that three isothiocyanates, sulforaphane,
      erucin, and iberin, are potent inducers of thioredoxin reductase 1 (TrxR1) in
      human breast cancer MCF-7 cells. Sulforaphane, erucin, and iberin at 1 microM
      induce TrxR1 mRNA 2-3-fold within 8 h of treatment, and induce mRNA 5-7-fold with
      12 microM ITC treatments. Selenium did not affect sulforaphane-induced TrxR1 mRNA
      levels, but significantly enhanced both TrxR1 protein expression (up to 9-fold in
      erucin treatment) and corresponding activities. These results suggest that
      dietary ITCs are important factors in the regulation of redox status through the
      induction of the selenoprotein thioredoxin reductase.

PMID- 15740017
TI  - Metabolites of conjugated isomers of alpha-linolenic acid (CLnA) in the rat.
AB  - Rumelenic (cis-9,trans-11,cis-15 18:3) acid is a naturally occurring conjugated
      isomer of alpha-linolenic acid (CLnA) in milk fat. Metabolism in rats was studied
      using a synthetic CLnA mixture, composed mainly by equimolar quantities of cis
      9,trans-11,cis-15 and cis-9,trans-13,cis-15 CLnA isomers. Their metabolisms were
      studied by feeding high quantities of CLnA (150 mg/day) for 4 days to rats that
      had been reared on a fatfree diet for 2 weeks. After this period, animals were
      sacrificed and liver and epididymal adipose tissue lipids extracted. Six
      metabolites of the cis-9,trans-11,cis-15 18:3 CLnA isomers were identified as
      being cis-7,trans-9,cis-13 16:3, cis-11,trans-13,cis-17 20:3, cis-8,cis-11,trans
      13,cis-17 20:4, cis-5,cis-8,cis-11,trans-13,cis-17 20:5, cis-7,cis-10,cis
      13,trans-15,cis-19 22:5, and cis-4,cis-7,cis-10,cis-13,trans-15,cis-19 22:6
      acids. Two metabolites of cis-9,trans-13,cis-15 18:3 CLnA isomer were also
      identified by GC-MS as being cis-7,trans-11,cis-13 16:3 and cis-5,cis-8,cis
      11,trans-15,cis-17 20:5.

PMID- 15740018
TI  - Nuclear magnetic resonance spectroscopic based studies of the metabolism of black
      tea polyphenols in humans.
AB  - Epidemiological studies indicate that a high intake of flavonoids is associated
      with an improved health status. Tea is one of the most abundant sources of
      flavonoids in the human diet. The bioavailability and biotransformation of tea
      flavonoids are, however, not clearly understood. The aim of the present study was
      to investigate the metabolism of black tea via a nonspecific screening method.
      (1)H nuclear magnetic resonance (NMR) spectroscopy was used to obtain
      nonselective profiles of urine samples collected from three human volunteers
      before and after a single dose of black tea. The complex spectroscopic profiles
      were interpreted with the use of pattern recognition techniques. Hippuric acid
      was confirmed as the major urinary black tea metabolite. One previously unknown
      metabolite was detected and identified as 1,3-dihydroxyphenyl-2-O-sulfate
      (sulfate conjugate of pyrogallol) using HPLC directly coupled to mass
      spectrometry and (1)H NMR spectroscopy. This study shows that NMR-pattern
      recognition studies can be used for the discovery of unknown flavonoid
      metabolites in humans.

PMID- 15740019
TI  - Piperidinyl amides with insecticidal activity from the maritime plant Otanthus
      maritimus.
AB  - Two new piperidine amides, N-[(2E,4E,8Z)-tetradecatrienoyl]piperidine (1) and N
      [(2E,4E,8Z,11Z)-tetradecatetrenoyl]piperidine (2), along with the known
      metabolites N-[(2E,4E)-tetradecadienoyl]piperidine (3), N-isobutyl-(2E,4E,)
      tetradecadienamide (4), N-isobutyl-(2E,4E,8Z)-tetradecatrienamide (5), N-isobutyl
      (2E,4E,8Z,11Z)-tetradecatetraenamide (6), sesamine (7), pinoresinol (8), and
      espeletone (9), were isolated from the dichloromethane/methanol extracts of the
      plant Otanthus maritimus Hoffman & Link collected from coastal areas in Greece.
      Pinoresinol (8) and espeletone (9) are reported for the first time as metabolites
      of O. maritimus. The structures of the new natural products were elucidated by
      interpretation of their NMR and high-resolution mass spectral measurements. The
      insecticidal properties of the crude extracts, essential oil, and isolated
      metabolites 1-9 were evaluated on Crematogaster scutellaris (Olivier) ants and
      Reticulitermes balkanensis (Clement) termites, showing significant levels of
      activity.

PMID- 15740020
TI  - Tumor cell proliferation and cyclooxygenase inhibitory constituents in
      horseradish (Armoracia rusticana) and Wasabi (Wasabia japonica).
AB  - Cyclooxygenase and human tumor cell growth inhibitory extracts of horseradish
      (Armoracia rusticana) and wasabi (Wasabia japonica) rhizomes upon purification
      yielded active compounds 1-3 from horseradish and 4 and 5 from wasabi rhizomes.
      Spectroscopic analyses confirmed the identities of these active compounds as
      plastoquinone-9 (1), 6-O-acyl-beta-d-glucosyl-beta-sitosterol (2), 1,2
      dilinolenoyl-3-galactosylglycerol (3), linolenoyloleoyl-3-beta-galactosylglycerol
      (4), and 1,2-dipalmitoyl-3-beta-galactosylglycerol (5). 3-Acyl-sitosterols,
      sinigrin, gluconasturtiin, and phosphatidylcholines isolated from horseradish and
      alpha-tocopherol and ubiquinone-10 from wasabi rhizomes isolated were inactive in
      our assays. At a concentration of 60 microg/mL, compounds 1 and 2 selectively
      inhibited COX-1 enzyme by 28 and 32%, respectively. Compounds 3, 4, and 5 gave
      75, 42, and 47% inhibition of COX-1 enzyme, respectively, at a concentration of
      250 microg/mL. In a dose response study, compound 3 inhibited the proliferation
      of colon cancer cells (HCT-116) by 21.9, 42.9, 51.2, and 68.4% and lung cancer
      cells (NCI-H460) by 30, 39, 44, and 71% at concentrations of 7.5, 15, 30, and 60
      microg/mL, respectively. At a concentration of 60 microg/mL, compound 4 inhibited
      the growth of colon, lung, and stomach cancer cells by 28, 17, and 44%,
      respectively. This is the first report of the COX-1 enzyme and cancer cell growth
      inhibitory monogalactosyl diacylglycerides from wasabi and horseradish rhizomes.

PMID- 15740021
TI  - Epicatechin and catechin in cocoa inhibit amyloid beta protein induced apoptosis.
AB  - To elucidate additional health benefits of cocoa phytochemicals on the
      neurotoxicity induced by amyloid beta protein (Abeta), PC12 cells were treated
      with toxic peptide (Abeta(25)(-)(35)) and the effects of epicatechin, catechin,
      and cocoa were studied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) reduction, lactate dehydrogenase (LDH) release, and trypan blue
      exclusion methods. Significant increase in neuronal cell death was observed on
      PC12 cells treated with Abeta(25)(-)(35) (25 microM), while epicatechin and
      catechin and their mixture prevented the Abeta-induced neuronal cell death. Abeta
      treatment also led to the increased membrane instability of PC12 cells. The
      membrane protective effects of the phenolics determined by LDH release and trypan
      blue exclusion assays demonstrated that epicatechin, catechin, and their mixture
      protect cellular membrane from Abeta-induced cytotoxicity. In these three
      different cell viability assays, the mixture of epicatechin and catechin showed
      the highest protective effect and synergistic activity. The present results
      showed that the major flavonoids of cocoa, epicatechin and catechin, protect PC12
      cells from Abeta-induced neurotoxicity, and suggest that cocoa may have anti
      neurodegenerative effect in addition to other known chemopreventive effects.

PMID- 15740022
TI  - Flax (Linum usitatissimum) seed cake: a potential source of high molecular weight
      arabinoxylans?
AB  - Water-soluble polysaccharides were extracted from flaxseed cake and analyzed. Two
      groups were separated by anion-exchange chromatography. The first one
      (nonretained) was the major fraction (83%) and possessed a high molecular weight
      (HMW) arabinoxylan (56%) with an Ara/Xyl ratio of 0.32 and an M(w) of 846 000.
      This polymer was accompanied by a smaller galactoglucan (44%), with an M(w) of
      6.5 x 10(4). The latter group (17%), retained by the gel, was further described
      as a HMW pectin heterogeneous group, with, respectively, 3.1 x 10(5) and 1.3 x
      10(5). Despite the presence of HMW arabinoxylans, the investigation of
      rheological flow sweep at the concentration of 2% (w/v) has shown a slight shear
      thinning behavior with a small zero-rate viscosity at 9.6 Pa.s.

PMID- 15740023
TI  - Degradation of Cry1Ab protein from genetically modified maize in the bovine
      gastrointestinal tract.
AB  - Immunoblotting assays using commercial antibodies were established to investigate
      the unexpected persistence of the immunoactive Cry1Ab protein in the bovine
      gastrointestinal tract (GIT) previously suggested by enzyme-linked immunosorbent
      assay (ELISA). Samples of two different feeding experiments in cattle were
      analyzed with both ELISA and immunoblotting methods. Whereas results obtained by
      ELISA suggested that the concentration of the Cry1Ab protein increased during the
      GIT passage, the immunoblotting assays revealed a significant degradation of the
      protein in the bovine GIT. Samples showing a positive signal in the ELISA
      consisted of fragmented Cry1Ab protein of approximately 17 and 34 kDa size. Two
      independent sets of gastrointestinal samples revealed the apparent discrepancy
      between the results obtained by ELISA and immunoblotting, suggesting that the
      antibody used in the ELISA reacts with fragmented yet immunoactive epitopes of
      the Cry1Ab protein. It was concluded that Cry1Ab protein is degraded during
      digestion in cattle. To avoid misinterpretation, samples tested positive for
      Cry1Ab protein by ELISA should be reassessed by another technique.

PMID- 15740024
TI  - Rice (Oryza sativa L.) containing the bar gene is compositionally equivalent to
      the nontransgenic counterpart.
AB  - This publication presents an approach to assessing compositional equivalence
      between grain derived from glufosinate-tolerant rice grain, genetic event
      LLRICE62, and its nontransgenic counterpart. Rice was grown in the same manner as
      is common for commercial production, using either conventional weed control
      practices or glufosinate-ammonium herbicide. A two-season multisite trial design
      provided a robust data set to evaluate environmental effects between the sites.
      Statistical comparisons to test for equivalence were made between glufosinate
      tolerant rice and a conventional counterpart variety. The key nutrients,
      carbohydrates, protein, iron, calcium, thiamin, riboflavin, and niacin, for which
      rice can be the principal dietary source, were investigated. The data demonstrate
      that rice containing the genetic locus LLRICE62 has the same nutritional value as
      its nontransgenic counterpart, and most results for nutritional components fall
      within the range of values reported for rice commodities in commerce.

PMID- 15740025
TI  - Cloning and sequence analysis of the phytoene synthase gene from a unicellular
      chlorophyte, Dunaliella salina.
AB  - Phytoene synthase (Psy) catalyzing the dimerization of two molecules of
      geranylgeranyl pyrophosphate (GGPP) to phytoene may be rate limiting for the
      synthesis of beta-carotene in Dunaliella salina. To elucidate the carotenogenic
      pathway in D. salina, the complete Psy gene was first isolated by genome walking
      technology and suppression PCR. Subsequently, RT-PCR was performed to obtain the
      Psy cDNA of 1260 bp, which codes 420 amino acids. The Psy gene of total length of
      2982 bp was found to consist of five exons and four introns when compared with
      the cDNA sequence. The D. salina Psy amino acid has a 78-89% similarity with many
      other higher plants, but a phylogenic analysis shows a closer relationship
      between the microalgal and cyanobacterial Psy.

PMID- 15740026
TI  - Characterization of Fe/Mn-superoxide dismutase from diatom Thallassiosira
      weissflogii: cloning, expression, and property.
AB  - A cDNA clone of 1114 bp encoding a putative Mn-superoxide dismutase (Mn-SOD) from
      diatom Thallassiosira weissflogii was cloned by the PCR technique. Nucleotide
      sequence analysis of this cDNA clone revealed that it was translated into 201
      amino acid residues. When the sequence was compared with Mn-SODs from Vibrio
      mimicus and Escherichia coli, as well as two Fe-SODs from E. coli and
      Photobacterium leiognathi, this SOD showed higher homology to Mn-SOD. The amino
      acid residues required to coordinate the single manganese ion were conserved in
      all reported Mn-SOD sequences. This cDNA was introduced in an expression vector,
      pET-20b(+), and transformed into E. coli BL21(DE3)pLysS. The expressed SOD
      protein was then purified by a His-tag column. The recombinant enzyme was heated
      at 55 degrees C with a time-dependent assay; the time interval for 50%
      inactivation was 23 min, and its thermal inactivation rate constant K(d) was 3.03
      x 10(-)(2) min(-)(1). The enzyme was inactivated either in acidic pH (below 4.0)
      or in the presence of imidazole (above 1.6 M) and had only a moderate effect
      under SDS (above 4%), whereas it was not affected under an alkaline pH (above
      9.0). The atomic absorption spectrometric assay showed that 0.6 atom of
      iron/manganese (3:1) was present in each subunit of SOD. Reconstitution study was
      suggested that diatom SOD was cambialistic (Fe/Mn)-SOD. The finding of this SOD
      cDNA could be used for a reference in comparing the differences among marine
      phytoplankton species and as a probe to detect the transcription level of this
      enzyme, which can be applied in cosmetics for skin protection or defending
      unesthetic effects caused by oxygen-containing free radicals.

PMID- 15740027
TI  - Enzymatic production of monoacylglycerols containing polyunsaturated fatty acids
      through an efficient glycerolysis system.
AB  - The aim of the study was to develop an efficient glycerolysis system for the
      enzymatic production of monoacylglycerols (MAGs) containing polyunsaturated fatty
      acids. Glycerolysis has been widely applied in industry for the chemical
      production of food MAGs under high temperature. The enzymatic glycerolysis system
      at 40-70 degrees C is unfortunately a multiphase system, which leads to the lower
      reaction efficiency. A tert-butyl alcohol system was developed after careful
      evaluation and more than 20-fold of the reaction efficiency from this system was
      obtained compared to the solvent-free system. Novozym 435 was employed as a
      catalyst in the glycerolysis from the screening. In the batch reaction system
      with tert-butyl alcohol, temperature higher than 40 degrees C was favored. The
      glycerol/oil ratio was best in the study with 4.5 while the solvent weight ratio
      from 1 to 3 had little effect. In general, 60-70% yield can be obtained at 2 h in
      the stirred tank reactor. The continuous glycerolysis was conducted in a packed
      bed reactor. MAG yield up to 70% was reached at 30-40 min residence time. The
      continuous glycerolysis was more sensitive to the amount of tert-butyl alcohol,
      and in the weight ratio to oil more than 2 was favored. The continuous process
      was optimized with the assistance of response surface methodology. Optimal
      conditions for the packed bed reactor after all considerations were recommended
      as glycerol/oil 4:1 (mol/mol), temperature 40 degrees C, and residence time 45
      min. The operation stability study showed that there was no slight reduction of
      reaction performance at more than 30 days, implying a high feasibility in
      practical applications.

PMID- 15740028
TI  - Fatty acids and fat-soluble vitamins in salted herring (Clupea harengus)
      products.
AB  - The fatty acid composition and contents of fat and fat-soluble vitamins of three
      salted products prepared from Icelandic herring were analyzed. The effects of
      storage on the products over their shelf life, 6 or 12 months, were investigated.
      The average oil content of salted, gutted herring and salted fillets in vacuum
      remained constant, 17 and 12% of wet weight, respectively. In the pickled product
      the oil content decreased during the 12 months of storage from 13 to 12%. The
      composition of the products was typical for herring, the most abundant fatty
      acids being oleic (18:1n-9), palmitic (16:0), cetoleic (22:1n-11), and gadoleic
      (20:1n-9) acids. Monounsaturated acids constituted clearly the main group with a
      proportion of >50% of all fatty acids. Eicosapentaenoic acid (EPA, 20:5n-3) and
      docosahexaenoic acid (DHA, 22:6n-3) comprised together >12% of all fatty acids.
      During storage, some hydrolysis of triacylglycerol (TAG) occurred, causing a
      slight reduction in practically all esterified fatty acids. In none of the three
      products was the loss of polyunsaturated fatty acids from TAG greater than the
      loss of saturated ones, indicating that the loss of EPA and DHA was not due to
      oxidation. After packing, the average content of vitamins A, D, and E in the
      products varied between 27 and 87 microg/100 g (wet weight), between 17-28
      microg/100 g (wet weight), and between 77-120 microg/100 g (wet weight),
      respectively. During storage, the level of vitamin A decreased significantly,
      whereas no loss of vitamin D was observed. The content of vitamin E was low in
      all products and showed wide variation. When compared to the recommended daily
      intake, it could be concluded that the products investigated were good and stable
      sources of long-chain n-3 fatty acids (EPA, DHA) and vitamin D.

PMID- 15740029
TI  - Photooxidative degradation of beer bittering principles: a key step on the route
      to lightstruck flavor formation in beer.
AB  - Isohumulones, dihydroisohumulones, tetrahydroisohumulones, and humulinones,
      important hop-derived bittering compounds in beer, were shown to give rise to
      reactive triacylmethyl radicals on interaction with triplet-excited riboflavin
      after spin trapping by 5,5-dimethyl-1-pyrroline N-oxide or 2-methyl-2
      nitrosopropane, followed by electron paramagentic resonance spectroscopy combined
      with spectral simulation. Electron abstraction from the ionized beta-tricarbonyl
      chromophore, which is common to all five-membered ring hop derivatives, is the
      initial event on photoinduced degradation. Radicaloid decomposition of
      isohumulones leads to precursors for 3-methylbut-2-ene-1-thiol, the lightstruck
      constituent in beer. Interaction of reduced derivatives of isohumulones with
      triplet-excited riboflavin furnished radical precursors of volatile aldehydes,
      which may lead to the development of unpleasant stale or cardboard flavors.

PMID- 15740030
TI  - Effect of far-infrared irradiation on the antioxidant activity of defatted sesame
      meal extracts.
AB  - To determine the effect of far-infrared (FIR) irradiation on the antioxidant
      activities of sesame meal, half of sesame seeds were FIR-irradiated and then oil
      was extracted from the seeds. The resulting defatted sesame meal (DSM) was
      extracted with methanol, and the antioxidant activities of methanolic extract
      were determined. FIR irradiation of sesame seeds for 30 min increased the total
      phenol content from 34.0 to 59.0 muM and radical scavenging activity of DSM
      extracts from 26.40 to 68.76%. The induction time of lipid oxidation of oil added
      to extracts was also retarded from 0.82 to 0.96 h. According to the gas
      chromatography-mass spectrometry analysis, several low molecular weight phenolic
      compounds, such as p-hydroxy benzoic acid, vanillic acid, p-coumaric acid,
      isoferulic acid, and o-coumaric acid, were frequently detected in FIR-irradiated
      DSM extracts as compared to unirradiated ones. These results indicated that FIR
      irradiation of sesame seeds increased the antioxidant activity of methanolic
      extracts of DSM.

PMID- 15740031
TI  - Potato peel extract-a natural antioxidant for retarding lipid peroxidation in
      radiation processed lamb meat.
AB  - The effective utilization of potato peel, a waste generated in large quantities
      by the food industry, as an antioxidant was investigated. Potato peel extract
      (PPE) exhibited high phenolic content (70.82 mg of catechin equivalent/100 g),
      chlorogenic acid (27.56 mg/100 g of sample) being the major component. The yield
      of total phenolics and chlorogenic acid increased by 26 and 60%, respectively,
      when the extract was prepared from gamma irradiated (150 Gy) potatoes. PPE showed
      excellent antioxidant activity as determined by beta-carotene bleaching and
      radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH). The
      suitability of PPE for controlling lipid oxidation of radiation processed lamb
      meat was also investigated. PPE (0.04%) when added to meat before radiation
      processing was found to retard lipid peroxidation of irradiated meat as measured
      by TBA number and carbonyl content. The antioxidant activity of PPE was found to
      be comparable to butylated hydroxytoluene (BHT).

PMID- 15740032
TI  - Effect of roasting on the formation of chlorogenic acid lactones in coffee.
AB  - Of all plant constituents, coffee has one of the highest concentrations of
      chlorogenic acids. When roasting coffee, some of these are transformed into
      chlorogenic acid lactones (CGL). We have studied the formation of CGL during the
      roasting of coffee beans in Coffea arabica cv. Bourbon; C. arabicacv. Longberry;
      and C. canephora cv. Robusta. Individual CGL levels were determined by comparison
      of HPLC peaks with those of synthetic CGL standards. Seven CGL were identified: 3
      caffeoylquinic-1,5-lactone (3-CQL), 4- caffeoylquinic-1,5-lactone (4-CQL), 3
      coumaroylquinic-1,5-lactone (3-pCoQL), 4-coumaroylquinic-1,5-lactone (4-pCoQL), 3
      feruloylquinic-1,5-lactone (3-FQL), 4-feruloylquinic-1,5-lactone (4-FQL), and 3,4
      dicaffeoylquinic-1,5-lactone (3,4-diCQL). 3-CQL was the most abundant lactone in
      C. arabica and C. canephora, reaching peak values of 230 +/- 9 and 254 +/- 4
      mg/100 g (dry weight), respectively, at light medium roast ( approximately 14%
      weight loss). 4-CQL was the second most abundant lactone (116 +/- 3 and 139 +/- 2
      mg/100 g, respectively. The maximum amount of CGL represents approximately 30% of
      the available precursors. The relative levels of 3-CQL and 4-CQL in roasted
      coffee were reverse to those of their precursors in green coffee. This suggests
      that roasting causes isomerization of chlorogenic acids prior to the formation of
      lactones and that the levels of lactones in roasted coffee do not reflect the
      levels of precursors in green coffee.

PMID- 15740034
TI  - Effects of temperature and sodium chloride concentration on the activities of
      proteases and amylases in soy sauce koji.
AB  - This study investigated the effects of temperature and sodium chloride
      concentration on the proteolytic and amylolytic activities of soy sauce koji. The
      optimal temperatures for both protease and amylase were found in the range of 50
      55 degrees C. The protease was not stable at 55 degrees C and retained only
      approximately 20% residual activity after incubation at 55 degrees C for 4 h. The
      protease was labile in sodium chloride solution, whereas the amylase was quite
      stable. The residual protease activity in an 18% NaCl solution was only
      approximately 3%. The harvested koji was mixed with 1.5 volumes of water (v/w)
      and incubated at 45 degrees C for 48 h; the total nitrogen and amino nitrogen
      contents were 1.3 and 0.56%, respectively. The results indicated that the
      hydrolysis of koji at the critical temperature of 45 degrees C could be employed
      as a rapid fermentation method to reduce the time for soy sauce manufacturing.
      According to this study, the combination of 5% sodium chloride and fermentation
      at 45 degrees C was considered as the best condition for the prohydrolysis of
      koji for making soy sauce. In addition, the critical temperature of 45 degrees C
      was very important when used in the preparation of protein hydrolysates for the
      flavoring industry and for the preparation of biologically active peptides.

PMID- 15740033
TI  - Oxidative stability of bovine serum albumin- and sodium caseinate-stabilized
      emulsions depends on metal availability.
AB  - Proteins often stabilize food emulsions and are also able to promote or delay
      lipid oxidation in complex systems. The purpose of this work was to investigate
      the relationship between metal ion availability and oxidative stability of oil-in
      water emulsions stabilized by bovine serum albumin (BSA) or sodium caseinate
      (NaCas). Emulsions with similar and stable droplet size distributions were
      prepared with stripped sunflower oil (30 vol %) and protein solutions (20 g L(
      )(1); pH = 6.5). In the absence of the water-soluble metal chelator EDTA, oxygen
      uptake, conjugated dienes, and volatile compounds developed faster in NaCas
      stabilized emulsions than in those prepared with BSA. This effect is attributed
      to the chelating properties of NaCas and to electrostatic interactions that
      attract some metal ions at the interface where they could initiate lipid
      oxidation. When EDTA (100 muM) was present, oxidation was delayed to a greater
      extent in emulsions made with NaCas than in BSA stabilized emulsions. These
      conditions probably enabled NaCas to exert free-radical-scavenging activity.

PMID- 15740035
TI  - Resveratrol treatment controls microbial flora, prolongs shelf life, and
      preserves nutritional quality of fruit.
AB  - Resveratrol is known as a grapevine secondary metabolite with fungicide activity.
      Its exogenous application on harvested grapes resulted in the reduction of
      microbial flora growth, and consequently, prolonged shelf life, without affecting
      the nutritional quality of the fruit. Resveratrol treatment also resulted in
      being effective on fruit that normally does not accumulate such metabolites as,
      for example, tomatoes, apples, avocado pears, and peppers. As a result, all
      treated fruits maintained their post-harvest quality and health longer than the
      untreated ones. This study demonstrates the potential use of resveratrol as a
      natural pesticide to reduce post-harvest fungi development on a broad spectrum of
      fruit types.

PMID- 15740036
TI  - Effects of phosphorus fertilizer supplementation on processing quality and
      functional food ingredients in tomato.
AB  - Even though several types of phosphorus fertilizers are used in crop production,
      the influence of phosphorus on produce quality is not well understood. Several
      quality attributes of tomato juice were analyzed in relation to phosphorus
      supplementation during a three-year field study (2000-2002). In addition to the
      recommended phosphorus fertilization, phosphorus supplementations, either through
      soil (low and high) or through foliar spray (hydrophos, seniphos), were tested.
      In general, soil and foliar phosphorus supplementation did not provide a
      statistically significant increase in yield. Tomato juice was evaluated for
      various quality characteristics including pH, titratable acidity, precipitate
      weight ratio, total solids, serum viscosity, Brookfield viscosity, color,
      lycopene levels, vitamin C, and flavor volatiles. Changes observed in several
      quality parameters were marginal, statistically insignificant and influenced by
      the season. Therefore, it appears that phosphorus supplementation may not
      significantly affect the processing quality parameters in tomato fruits.

PMID- 15740037
TI  - Effects of phosphorus fertilizer supplementation on antioxidant enzyme activities
      in tomato fruits.
AB  - The effects of soil and foliar phosphorus supplementation on the activities and
      levels of superoxide dismutase (SOD), guaiacol peroxidase (POX), and ascorbate
      peroxidase (APX) in tomato fruits were evaluated by determining enzyme activities
      and isoenzyme analysis. Both protein levels and enzyme activities varied
      depending on the variety and season. In general, phosphorus supplementation did
      not alter SOD, POX, and APX activities significantly;however, some treatments
      showed season- and stage-specific enhancement in activities as noticed with
      hydrophos and seniphos supplementation. Three different SOD isozymes were
      observed, and these isozymes showed very similar staining intensities in response
      to P application and during the three developmental stages studied. Two major
      isozymes of POX and two different APX isozymes were observed at all the
      developmental stages. The results suggest that antioxidant enzyme activities may
      be influenced by the availability of phosphorus, but are subject to considerable
      variation depending on the developmental stage and the season.

PMID- 15740038
TI  - Methyl esterification divergently affects the degradability of pectic uronosyls
      in nonlignified and lignified maize cell walls.
AB  - Nonlignified cell walls from Zea mays (L.) cell suspensions were incubated with
      and without pectin methylesterase (PME) and a portion were artificially lignified
      to assess how methyl esters influence the release of pectic uronosyls and total
      sugars from cell walls by fungal enzymes. Treatment with PME reduced uronosyl
      concentrations from 97 to 92 mg/g, reduced uronosyl methylation from 57% to 21%,
      and increased Klason lignin concentrations in artificially lignified cell walls
      from 99 to 116 mg/g. Although PME treatment slightly enhanced uronosyl release
      from nonlignified cell walls, it reduced uronosyl release from artificially
      lignified cell walls by 55% after 4 h and by 7% after 72 h of enzymatic
      hydrolysis. Pectin hydrolysis in PME treated cell walls was probably impaired by
      enhanced benzyl ester cross-linking of uronosyls to lignin via quinone methide
      intermediates. Variations in uronosyl methylation had little effect on the
      overall release of total sugars from cell walls.

PMID- 15740039
TI  - Near-infrared reflectance model for the rapid prediction of total fat in cereal
      foods.
AB  - AOAC method 996.01, used in cereal foods to determine total fat as defined by the
      U.S. Nutrition Labeling and Education Act (NLEA), is laborious and time-consuming
      and utilizes hazardous chemicals. Near-infrared (NIR) reflectance spectroscopy, a
      rapid and environmentally benign technique, was investigated as a potential
      method for the prediction of total fat using AOAC method 996.01 as the reference
      method. Near-infrared reflectance spectra (1104-2494 nm) of ground cereal
      products (n = 72) were obtained using a dispersive spectrometer, and total fat
      was determined according to AOAC method 996.01. Using multivariate analysis, a
      modified partial least-squares model was developed for total fat prediction. The
      model had a SECV of 1.12% (range = 0.5-43.2%) and a multiple coefficient of
      determination of 0.99. The model was tested with independent validation samples
      (n = 36); all samples were predicted within NLEA accuracy guidelines. The results
      indicate that NIR reflectance spectroscopy is an accurate means of determining
      the total fat content of diverse cereal products for nutrition labeling.

PMID- 15740040
TI  - Characterization and quantification of free and esterified 9- and 13
      hydroxyoctadecadienoic acids (HODE) in barley, germinating barley, and finished
      malt.
AB  - The analysis of (R)-9- and (S)-9-hydroxy-10E,12Z-octadecadienoic acid as well as
      (R)-13- and (S)-13-hydroxy-9Z,11E-octadecadienoic acid (HODE) as free acids,
      esterified in triacylglycerols (storage lipids), and esterified in polar lipids
      (phospholipids, glycolipids, etc.) in barley, germinating barley, and finished
      malt was performed using [13-(18)O(1)]-(S)-13-HODE isotope dilution assays with
      GC-MS and straight- and chiral-phase HPLC. 9- and 13- HODE occur approximately
      racemically in barley, indicating an autoxidation. The enantiomeric excesses
      increase to 78% S for free 9-HODE and to 58% S for free 13-HODE in germinating
      barley as a result of lipoxygenase-2 (LOX-2) catalysis, but free HODEs are at low
      concentration. More than 90% of HODEs in barley and malt are esterified. In the
      storage lipids of green malt 53 mg/kg 9-HODE and 147 mg/kg 13-HODE were detected.
      This ratio of 30:70 reflects the regioselectivity of the LOX-2 enzyme in malt. In
      the polar lipids 45 mg/kg 9-HODE and 44 mg/kg 13-HODE were characterized. The
      latter indicate a hitherto unknown 9-lipoxygenase activity with polar lipids as
      substrates. During kilning the contents of most HODEs decreased significantly due
      to chemical and enzymatic degradation, whereas polar-esterified (R)-13-HODE
      increased (43%) in the finished malt.

PMID- 15740041
TI  - Screening of mango (Mangifera indica L.) cultivars for their contents of flavonol
      O- and xanthone C-glycosides, anthocyanins, and pectin.
AB  - With respect to their browning potential and in consideration of a combined
      recovery of pectin and phenolic compounds, peels of 14 cultivars and the flesh of
      nine cultivars of mango (Mangifera indica L.) fruits were analyzed for their
      contents of flavonol O- and xanthone C-glycosides by high-performance liquid
      chromatography (HPLC)-diode array detection-electrospray ionization mass
      spectrometry (ESI-MS). While total amounts of up to 4860 mg/kg dry matter
      demonstrated the peels to be a rich source of phenolic compounds, only traces
      could be detected in the flesh. The profile of flavonol glycosides of the peels
      proved to be highly characteristic and may therefore serve as a tool for
      authenticity control of mango puree concentrate, which is often produced from
      unpeeled fruits and represents an important intermediate for the production of
      mango nectars. Two compounds were isolated by preparative HPLC, and their
      structures were elucidated on the basis of ESI-MS as well as NMR spectroscopy,
      establishing the two compounds as rhamnetin 3-O-beta-galactopyranoside and
      rhamnetin 3-O-beta-glucopyranoside, respectively. In the peels of red-colored
      cultivars, cyanidin 3-O-galactoside and an anthocyanidin hexoside so far not
      reported in mango could tentatively be identified. The contents and degrees of
      esterification of pectins extracted from the lyophilized peels ranged from 12.2
      to 21.2% and from 56.3 to 65.6%, respectively, suggesting mango peels also as a
      promising source of high-quality pectin.

PMID- 15740042
TI  - Determination of phosphorus fractions in animal protein ingredients.
AB  - Phosphorus (P) is present in different chemical compounds in animal feeds, and
      the solubility and digestibility of these different compounds are known to differ
      significantly. Animal protein ingredients generally have a high P content and are
      major contributors to total P of feeds for fish and other domestic animals.
      Estimation of different P compounds in these ingredients could help to improve
      the accuracy of estimates of digestible P contents of feeds. Bone P and organic P
      contents were quantified in 32 animal protein ingredients, including 10 fish
      meals, 14 meat and bone meals, and 8 poultry byproducts meals, using a
      fractionation protocol. The total P contents of the ingredients ranged from 2.1
      to 8.3% on a dry matter (DM) basis. Organic P contents varied between 0.3 and
      1.3% of DM. Highly significant (p < 0.001) linear relationships were observed
      between total P and ash and between bone P and ash for all ingredients combined:
      total P (%) = 0.185 x ash (%) (R (2) = 0.88), and bone P (%) = 0.188 x ash (%) -
      0.852 (R (2) = 0.94). These results suggest that bone P can be easily and
      reliably estimated on the basis of ash content in animal protein ingredients.

PMID- 15740043
TI  - Sequential extraction and quantitative recovery of gliadins, glutenins, and other
      proteins from small samples of wheat flour.
AB  - Methods to sequentially extract and fractionate wheat flour proteins were
      evaluated to reliably quantify gliadins, glutenins, and albumins/globulins in
      single flour samples. Compositions of the resulting protein fractions were
      analyzed by RP-HPLC combined with SDS-PAGE. Unknown proteins were identified by
      mass spectrometry or N-terminal sequencing. The best separation and recovery of
      discrete albumin/globulin, gliadin, and glutenin fractions from the same flour
      sample was achieved by extraction with 0.3 M NaI in 7.5% 1-propanol followed by
      2% SDS, 25 mM DTT in 25 mM TRIS, pH 8.0, and precipitation of the solubilized
      proteins with ammonium acetate/methanol followed by acetone. Average flour
      composition for the variety Butte86 was 10% albumin/globulin, 40% gliadin, and
      48% glutenin. This method should be useful for determining flour composition in
      diverse samples and evaluating relationships between proteins and end-use
      functionality.

PMID- 15740044
TI  - Characterization of two Acanthoscelides obtectus alpha-amylases and their
      inactivation by wheat inhibitors.
AB  - Wheat alpha-amylase inhibitors represent an important tool in engineering crop
      plants against bean bruchids. Because Acanthoscelides obtectus is a devastating
      storage bean insect-pest, we attempted to purify and characterize its gut alpha
      amylases, to study their interaction with active proteinaceous inhibitors. Two
      digestives alpha-amylases (AoA1 and AoA2) were purified from gut larvae, showing
      molecular masses of 30 and 45 kDa for each one, respectively. The stoichiometry
      interaction between these alpha-amylases with two wheat inhibitors (0.19 and
      0.53) showed a binding complex of 1:1 enzyme:inhibitor. In vivo activities of
      these inhibitors against A. obtectus were also evaluated using a rich ammonium
      sulfate inhibitor fraction (F(20)(-)(40)) and purified inhibitors after reversed
      phase high-performance liquid chromatography columns. Incorporation of three
      different inhibitor concentrations (0.25, 0.5, and 1.0% w/w) into artificial
      seeds showed that addition of the purified 0.19 inhibitor at the highest
      concentration (1.0%) reduced the larval weight by 80%. Similar data were observed
      when 0.53 inhibitor was incorporated at 0.5%. When the concentration of purified
      0.53 was enhanced to 1.0%, no larvae or adult emergence were observed. Our data
      suggest that these alpha-amylase inhibitors present great potential for use in
      Phaseolus genetic improvement programs.

PMID- 15740045
TI  - Comparison of chemical characteristics of three soybean cysteine proteinase
      inhibitors.
AB  - Three recombinant soybean cysteine proteinase inhibitors (rSCPIs) L1, R1, and N2
      were chemically characterized. These inhibitors have the potential to inhibit the
      growth and development of three major agricultural crop pests known to utilize
      cysteine proteinases (CPs) for protein digestion: Western corn rootworm, Colorado
      potato beetle, and cowpea weevil. Characterization data obtained show differences
      between the inhibitors and will be needed to consider the use of rSCPIs to create
      insect resistance in plants.

PMID- 15740046
TI  - Metabolites inhibiting germination of Orobanche ramosa seeds produced by
      Myrothecium verrucaria and Fusarium compactum.
AB  - Myrothecium verrucaria and Fusarium compactum were isolated from diseased
      Orobanche ramosa plants collected in southern Italy to find potential biocontrol
      agents of this parasitic weed. Both fungi grown in liquid culture produced
      metabolites that inhibited the germination of O. ramosa seeds at 1-10 muM. Eight
      metabolites were isolated from M. verrucaria culture extracts. The main
      metabolite was identified as verrucarin E, a disubstituted pyrrole not belonging
      to the trichothecene group. Seven compounds were identified by spectroscopic
      methods as macrocyclic trichothecenes, namely, verrucarins A, B, M, and L
      acetate, roridin A, isotrichoverrin B, and trichoverrol B. The main metabolite
      produced by F. compactum was neosoloaniol monoacetate, a trichothecene. All the
      trichothecenes proved to be potent inhibitors of O. ramosa seed germination and
      possess strong zootoxic activity when assayed on Artemia salina brine shrimps.
      Verrucarin E is inactive on both seed germination and zootoxic assay.

PMID- 15740047
TI  - Binding model construction of antifungal 2-aryl-4-chromanones using CoMFA,
      CoMSIA, and QSAR analyses.
AB  - Flavonoids, generated by plants upon attack by a range of pathogens, are
      demonstrated to have a role in biotic and abiotic stress response phenomena in
      plants, and there is increasing evidence for the antibacterial, antifungal, and
      antiviral activities of these compounds. Using the bioisosterism strategy, a
      series of 2-aryl-4-chromanone derivatives based upon the structure of flavanones,
      a kind of flavonoid phytoalexins, were synthesized and tested for the antifungal
      activity against Pyricularia grisea, which have been reported in our previous
      papers. To further explore the comprehensive structure-activity relationship and
      construct the binding model for the antifungal compounds, two kinds of molecular
      field analysis techniques, comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA), were performed
      following a Hansch-Fujita QSAR study. Superimpositions were performed using three
      alignment rules, that is, centroid-based alignment, common substructure-based
      alignment, and field fit alignment, and statistically reliable models with good
      predictive power (CoMFA r(2) = 0.952, q(2) = 0.727; CoMSIA r(2) = 0.965, q(2) =
      0.751) were achieved on the basis of the common substructure-based alignment. The
      combined results of CoMFA, CoMSIA, and former Hansch-Fujita QSAR analyses
      resulted in comprehensive understanding about the structure-activity
      relationships, which led to this construction of a plausible binding model of the
      title compounds.

PMID- 15740048
TI  - Adsorption of atrazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine
      onto Fe(III) polyhydroxy cations intercalated vermiculite and montmorillonite.
AB  - This paper describes the modification of the clay minerals vermiculite (VT) and
      montmorillonite (MT) by intercalating Fe(III) polymers of different [OH(
      )]:[Fe(III)] ratios with the aim of removing atrazine (AT) and its metabolites
      deethylatrazine (DEA), deisopropylatrazine (DIA), and hydroxyatrazine (ATOH) from
      aqueous solution. An enhancement of adsorption capacity was observed for both
      intercalated clay minerals in comparison to the potassium-saturated materials
      (KVT or KMT). The results showed that different [OH(-)]:[Fe(III)] molar ratios
      had a small influence on the adsorption capacity, as well as in the basal
      spacing, BET surface area, and porosity. For the lowest initial concentrations of
      AT, DIA, and ATOH (0.050 mg L(-)(1)) studied, the modified VT adsorbed almost 80%
      of AT and DIA, while ATOH was removed at concentration levels below the detection
      limit of the technique, implying in at least 99.5% of sorption. Weak interaction
      between intercalated VT and DEA was observed, although a significant adsorption
      enhancement occurred in comparison to KVT. Within a 24 h interval, desorption of
      AT and DIA in aqueous medium reached levels close to 20% of the amount initially
      adsorbed, while for ATOH only 3% of the adsorbed compound was desorbed. The
      adsorption capacity of the Fe(III)-intercalated VT decreased after the first
      adsorption/desorption cycle, implying that the material is not suitable for
      reutilization. The intercalated MT was a powerful sorbent for AT, DEA, DIA, and
      ATOH, removing all of these chemicals from solution almost quantitatively
      (sorption greater than 99.5%), even at initial concentrations as high as 1.0 mg
      L(-)(1). Additionally, desorption of AT, ATOH, and DIA in water was not
      measurable up to the tube corresponding to the initial concentration of 1.0 mg L(
      )(1), suggesting strong irreversible binding of these compounds to the
      intercalated MT materials. Desorption of DEA from the intercalated MT was between
      5 and 30%. Unlike what was observed for VT, the intercalated MT materials were
      recyclable, keeping an excellent performance when reutilized.

PMID- 15740049
TI  - Organoclay formulations of acetochlor: effect of high salt concentration.
AB  - This study aimed to evaluate new methodology for designing ecologically
      acceptable formulations of acetochlor. Modification of montmorillonite with
      phenyltrimethylammonium chloride (PTMA) or benzyltrimethylammonium chloride
      (BTMA) and organoclay formulations of acetochlor were prepared in the presence of
      high concentrations of sodium chloride (150 g/L). Acetochlor concentration in the
      equilibrium solutions was determined by HPLC. Release of acetochlor in a water
      system was performed by a funnel experiment. Leaching of acetochlor in soil was
      determined by a bioassay using a column technique and Setaria viridis as a test
      plant. The adsorbed amounts of acetochlor on montmorillonite exchanged by PTMA or
      BTMA were increased as NaCl concentration increased in the equilibrium solution.
      Leaching of acetochlor from organoclay formulations was significantly inhibited
      to the top soil layer (0-5 cm) when the formulations were prepared at extreme
      NaCl concentration (100-150 g/L). These results are in accord with a funnel
      experiment that showed a reduction in acetochlor release from the montmorillonite
      based formulations. The application of this method for herbicide formulation
      would produce ecologically acceptable herbicide formulations that can
      significantly minimize the risk to groundwater pollution.

PMID- 15740050
TI  - Human pharmaceuticals, hormones, and personal care product ingredients in runoff
      from agricultural fields irrigated with treated wastewater.
AB  - Irrigation of crops with treated wastewater has the potential to introduce
      effluent-derived organic microcontaminants into surface waters through
      agricultural runoff. To determine whether compounds indicative of the presence of
      treated effluent in irrigation water could be identified in agricultural runoff,
      surface runoff samples collected from effluent-irrigated and rain-fed cultivated
      fields were analyzed for a broad spectrum of organic compounds. A variety of
      compounds was identified that appeared to be associated with irrigation with
      treated wastewater. These compounds included human pharmaceuticals (e.g.,
      carbamazepine, gemfibrozil, carisoprodol), personal care product ingredients
      (e.g., insect repellent, polycyclic musks), and alkyl phosphate flame retardant
      chemicals. Most of these compounds appear not to have been previously reported in
      agricultural runoff. These compounds were present at concentrations below the few
      published aquatic toxicology data available; however, their potential to elicit
      more subtle effects in aquatic organisms cannot be excluded. None of these
      compounds were detected by broad-spectrum analysis in samples from the same
      fields during runoff-producing rain events.

PMID- 15740051
TI  - Terpene compounds as possible precursors of 1,8-cineole in red grapes and wines.
AB  - While the contribution of 1,8-cineole to the aroma of wine has been reported, it
      is a matter of controversy that the vineyards producing such wines are surrounded
      by Eucalyptus trees, which may contribute their essence to the grapes. However,
      experimental information presented in this paper suggests that 1,8-cineole can be
      produced by chemical transformation of limonene and alpha-terpineol, and this
      process may be responsible for the occurrence of Eucalyptus-like aroma in Tannat
      wines from vines not grown in the vicinity of Eucalyptus trees. A mechanism for
      the chemical transformation of these aroma compounds is proposed.

PMID- 15740052
TI  - Identification of potent odorants in different cultivars of snake fruit [Salacca
      zalacca (Gaert.) Voss] using gas chromatography-olfactometry.
AB  - Three cultivars of snake fruits, Pondoh Hitam, Pondoh Super, and Gading, were
      freshly extracted using liquid-liquid extraction. The aroma compounds of the
      three samples were analyzed by GC-MS and GC-olfactometry using the nasal impact
      frequency (NIF) method. A total of 24 odor-active compounds were associated with
      the aroma of snake fruit. Methyl 3-methylpentanoate was regarded as the character
      impact odorant of typical snake fruit aroma. 2-Methylbutanoic acid, 3
      methylpentanoic acid, and an unknown odorant with very high intensity were found
      to be responsible for the snake fruit's sweaty odor. Other odorants including
      methyl 3-methyl-2-butenoate (overripe fruity, ethereal), methyl 3-methyl-2
      pentenoate (ethereal, strong green, woody), and 2,5-dimethyl-4-hydroxy-3[2]
      furanone (caramel, sweet, cotton candy-like) contribute to the overall aroma of
      snake fruit. Methyl dihydrojasmonate and isoeugenol, which also have odor impact,
      were identified for the first time as snake fruit volatiles. The main differences
      between the aroma of Pondoh and Gading cultivars could be attributed to the
      olfactory attributes (metallic, chemical, rubbery, strong green, and woody),
      which were perceived by most of the panelists in the Pondoh samples but were not
      detected in the Gading samples. This work is a prerequisite for effective
      selection of salak genotypes with optimal aroma profiles for high consumer
      acceptance.

PMID- 15740053
TI  - Characteristic odor components of kumquat (Fortunella japonica Swingle) peel oil.
AB  - This study was conducted to determine the composition of kumquat (Fortunella
      japonica Swingle) cold-pressed peel oil and to determine which volatile
      components are primarily responsible for the aroma of this oil. Eighty-two
      compounds were identified in the oil by GC and GC-MS. The major compounds were
      limonene (93.73%), myrcene (1.84%), and ethyl acetate (1.13%). Flavor dilution
      (FD) factors and relative flavor activities (RFA) of volatile constituents were
      evaluated by aroma extract dilution analysis with gas chromatography-olfactometry
      (GC-O). Camphene, terpinen-4-ol, citronellyl formate, and citronellyl acetate
      showed high FD factors (>/=5) and RFA (>20). Citronellyl formate and citronellyl
      acetate were regarded as the characteristic odor components of the kumquat peel
      oil from the results of FD factor, RFA, and GC-sniffing. Citronellyl acetate is
      considered to be the odor component most similar to kumquat by organoleptic
      evaluation with GC-O.

PMID- 15740054
TI  - Impact of the suppression of lipoxygenase and hydroperoxide lyase on the quality
      of the green odor in green leaves.
AB  - Most of the volatile compounds responsible for the "green" notes to the aroma of
      fruits and vegetables are produced by the degradation of polyunsaturated fatty
      acids through the lipoxygenase pathway. The most determinant steps of this
      pathway are the peroxidation of free linoleic or linolenic acid by the action of
      lipoxygenase and then the lysis of the resulting hydroperoxides through a
      reaction catalyzed by the hydroperoxide lyase. This work analyzes the impact of
      the depletion of these enzymes on the volatile composition of leaves from potato
      plants. A characterization of the volatile profiles of the different potato
      mutants, a study of the metabolism of radiolabeled linoleic acid, and a
      determination of lipoxygenase activity have been carried out. The depletion of
      hydroperoxide lyase induced an increase in the lipoxygenase activity and the
      content of C5 volatiles, whereas the lipoxygenase silencing caused a severe
      decrease in the amount of volatiles produced by the leaves and always in the
      intensity of their aroma. The changes in the sensory evaluation of leaf aroma, as
      correlated to depletion of the two enzymes, have been investigated. The
      perspectives of producing vegetable products with a modified aroma by genetic
      engineering are discussed in light of the statistical results.

PMID- 15740055
TI  - Effect of solution conductivity on the volatile constituents of Origanum
      dictamnus L. in nutrient film culture.
AB  - The chemical composition of the essential oils obtained from leaves and bracts of
      hydroponically cultivated Origanum dictamnus L. (Cretan dittany), growing under
      various electrical conductivity (EC) levels (2.0, 4.0, and 6.0 mS/cm), was
      studied, using the nutrient film technique (NFT). The analysis of the essential
      oil content was achieved by GC-MS technique, and totals of 41 and 38 different
      compounds were identified in both cases of large-leaved and narrow-leaved samples
      of leaves and bracts, respectively. Differences in the composition content and of
      the percentage of each of the constituents in the two studied samples (i.e.,
      large-leaved and narrow-leaved) and within the essential oils of leaves and
      bracts in both samples were observed. Carvacrol and p-cymene were identified as
      the main constituents in all essential oils, whereas thymoquinone was found in
      higher percentage in the essential oils of large-leaved than in narrow-leaved
      plants. The results obtained from GC-MS analysis were submitted to chemometric
      analysis, and a phenotypic similarity of the essential oils of narrow-leaved O.
      dictamnus was observed, whereas the essential oils of large-leaved O. dictamnus
      showed two separate subgroups.

PMID- 15740056
TI  - Investigation of the retronasal perception of strawberry aroma aftersmell
      depending on matrix composition.
AB  - The development of strawberry aroma aftersmell after consumption in aqueous and
      milk model systems was followed. A recently developed sensory approach was used
      to seize the qualitative, quantitative, and temporal aspects of aroma profile
      development. The results obtained from sensory evaluation were then correlated to
      analytical data, obtained by means of intraoral aroma detection using the buccal
      odor screening system (BOSS). A clear correlation was found between the sensory
      persistence of single odor impressions and the intraoral detectability of
      odorants by BOSS. For the strawberry aroma mixture it could be shown that BOSS is
      capable of selecting those odorants of a complex aroma mixture that elicit a
      certain aftersmell impression developing after a certain period of time in the
      oral cavity. Also, the changes in in vivo odorant persistence depending on
      changes in food matrix composition could be directly followed by means of BOSS.

PMID- 15740057
TI  - Interaction of soluble peptides and proteins from skeletal muscle with volatile
      compounds in model systems as affected by curing agents.
AB  - The effect of curing agents (salt, glucose, nitrate, nitrite, and ascorbic acid)
      on the binding of skeletal peptides (carnosine and anserine) and a sarcoplasmic
      protein (myoglobin) with key flavor compounds (hexanal, octanal, 2-pentanone, 2
      methylbutanal, and 3-methylbutanal) has been studied by solid-phase
      microextraction (SPME). Curing agents had an effect on the interaction process
      between carnosine and volatile compounds, which was higher than the interactions
      observed with anserine and myoglobin. Sodium chloride decreased the interaction
      of volatiles with carnosine except for octanal, which was increased, and 2
      pentanone, which was unaltered. Ascorbic acid exerted the highest effect by
      decreasing the interaction of carnosine with all of the volatile compounds except
      for octanal and 2-pentanone. The interaction with anserine was affected by sodium
      chloride, nitrate, and nitrite, producing a decrease in the interaction with
      hexanal, octanal, and methional. Finally, sodium chloride, glucose, and nitrite
      increased the interaction of myoglobin with hexanal, octanal, and methional. The
      effect of simulated stages of the curing process on the binding was also studied.
      A combined effect of the curing agents resulted in a change in the relative
      proportions of volatile compounds that can lead to different flavor perceptions
      of dry-cured meat products.

PMID- 15740058
TI  - Volatile compounds of Aspergillus strains with different abilities to produce
      ochratoxin A.
AB  - Volatile compounds emitted by Aspergillus strains having different abilities to
      produce ochratoxin A were investigated. Thirteen strains of Aspergillus
      ochraceus, three belonging to the A. ochraceus group, and eight other species of
      Aspergillus were examined for their abilities to produce volatile compounds and
      ochratoxin A on a wheat grain medium. The profiles of volatile compounds,
      analyzed using SPME, in all A. ochraceus strains, regardless of their
      toxeginicity, were similar and comprised mainly of 1-octen-3-ol, 3-octanone, 3
      octanol, 3-methyl-1-butanol, 1-octene, and limonene. The prevailing compound was
      always 1-octen-3-ol. Mellein, which forms part of the ochratoxin A molecule, was
      found in both toxigenic and nontoxigenic strains. Volatile compounds produced by
      other Aspergillus strains were similar to those of A. ochraceus. Incubation
      temperatures (20, 24, and 27 degrees C) and water content in the medium (20, 30,
      and 40%) influenced both volatile compounds formation and ochratoxin A
      biosynthesis efficiency, although conditions providing the maximum amount of
      volatiles were different from those providing the maximum amount of ochratoxin A.
      The pattern of volatiles produced by toxigenic A. ochraceus strains does not
      facilitate their differentiation from nontoxigenic strains.

PMID- 15740059
TI  - Aroma impact components in commercial plain sufu.
AB  - Volatile components of three commercial plain sufus or fermented soybean (Glycine
      max) curds (A-C) were extracted by a supercritical fluid extraction apparatus and
      analyzed by gas chromatography-mass spectrometry. A total of 83 compounds were
      found, of which 68 compounds were common among the three samples. Samples A, B,
      and C had 76, 75, and 74 components, respectively. Alcohols (17), acids (15), and
      esters (16) were the major classes. The rest of the classes were miscellaneous
      compounds (9), aldehydes (7), alkanes (5), aromatic compounds (5), ketones (3),
      furans (2), S-containing compounds (2), and other N-containing compounds (2). Gas
      chromatography-flame ionization detection-olfactometry analyses identified 17
      potent odorants with different odor descriptions such as sour, sweet, fruity,
      coconut-like, and meaty. Fourteen odorants were further pinpointed by omission
      experiments among the 17 to be critical to the odor of commercial plain sufu.
      Acetic acid, methional, ethyl (Z,Z)-9,12-octadecadienoate, ethyl (Z)-9
      ocatadecenoate, and 3-methylbutanoic acid were some of the potent odorants found.

PMID- 15740060
TI  - Quality components of sea buckthorn (Hippophae rhamnoides) varieties.
AB  - The sensory quality and chemical constituents of juices from seven sea buckthorn
      (Hippophaerhamnoides L.) varieties were studied in two consecutive seasons. The
      juices were generally described as sour and astringent, with low sweetness and
      fruity flavor. The differences in sensory quality as well as in chemical
      composition between samples and years were significant (p < 0.05) in most
      parameters studied. The Chuiskaya variety was described as the sweetest, with the
      strongest fruity flavor, whereas the varieties Avgustinka, Botanicheskaya,
      Trofimovskaya, and Raisa were the sourest and most astringent. Total sugar
      (fructose and glucose) varied from 1.9 to 7.1 g/100 mL in juice, total acid
      (malic and quinic acids) from 3.1 to 5.1 g/100 mL, vitamin C from 29 to 176
      mg/100 mL, and pulp oil from 0.7 to 3.6%. The soluble solids were between 7.4 and
      12.6, the pH between 2.7 and 2.9, and the titrable acidity between 2.0 and 3.7.
      The redness was highest on Avgustinka and Raisa, but there were no differences in
      yellowness. Total sugar and the sugar/acid ratio correlated positively with
      sweetness and negatively with sourness and astringency, whereas total acid and
      titrable acidity correlated positively with sourness and astringency and
      negatively with sweetness.

PMID- 15740061
TI  - Aroma release and delivery following the consumption of beverages.
AB  - Processes controlling aroma release and delivery during and after the consumption
      of a beverage were studied using real-time physiological and aroma release
      measurements. The key processes were as follows. During swallowing, a portion of
      the buccal gas phase was transferred first to the throat and then to the nasal
      passages via the tidal breath flow. This mechanism accounted for the sharp pulse
      of aroma seen at the beginning of the swallow breath and on subsequent swallows.
      The persistence effect was due to liquid-air partition from beverage coated on
      the throat and was dependent on the concentration of volatile compounds in the
      beverage. Lipid in the beverage caused a decrease in the intensity of volatile
      compounds on the breath, but the presence of a thickening agent had no effect on
      persistence.

PMID- 15740062
TI  - Enrichment of cheeses manufactured from cow's and sheep's milk blends with sheep
      like species-related alkylphenols.
AB  - Enhancement of concentrations of species-related sheep-like alkylphenols, p- and
      m-cresols and 3- and 4-ethylphenols, in experimental Manchego-type cheeses
      manufactured from cow's and sheep's milk blends (80:20) by using arylsulfatases
      was investigated. A food-grade arylsulfatase from Aspergillus oryzae (ATCC 20719)
      was produced using a stimulatory medium, and crude dried cells were used as the
      enzyme source. Exogenous arylsulfatases from Helix pomatia and A. oryzae were
      added to cheese curd, and the amounts of species-related alkylphenols were
      measured. Arylsulfatase from H. pomatia released limited amounts of alkylphenols
      in the cheese only when used at a high level. Arylsulfatase from A. oryzae
      released substantial amounts of alkylphenols during 2 months of ripening. The
      concentrations of alkylphenols in A. oryzae arylsulfatase-treated cheese were
      comparable to the previously reported levels present in aged Manchego-type
      cheeses manufactured from pure sheep's milk.

PMID- 15740063
TI  - Identification of 8-nonenal as an important contributor to "plastic" off-odor in
      polyethylene packaging.
AB  - Food and beverage products stored in polyethylene (PE) containers may absorb some
      of PE's volatile minor components and become tainted by its characteristic
      "plastic" odor. High-density PE containers that had imparted "plastic" odor to an
      experimental corn chip product were analyzed by simultaneous
      distillation/extraction to remove the volatile components, by gas
      chromatography/olfactometry (GC/O) to locate the offending components and by 2-D
      GC/mass spectrometry (MS) to identify the major "plastic" odor contributor (8
      nonenal). The identification was made using high-resolution electron ionization
      and chemical ionization MS data to narrow the possibilities to two isomers of
      nonenal, followed by retrieval of reference spectra and confirmatory synthesis.
      By monitoring 8-nonenal in HDPE containers and corn chips it was demonstrated
      that 8-nonenal tracks with "plastic" aroma observed in containers and with
      "plastic" flavor observed in corn chips stored in the containers.

PMID- 15740064
TI  - Influence of maturation on the alteration of allergenicity of green pea (Pisum
      sativum L.).
AB  - The IgE-binding capacity of different maturation levels of green pea seeds (Pisum
      sativum L.) of the variety Maxigolt is examined to determine the influence of
      maturation on the alteration of allergenicity. Different protein extraction
      methods to get total protein extracts and the protein fractions glutelin,
      globulin, and albumin from different maturation levels of green pea seeds are
      applied to SDS-PAGE/silver staining as well as SDS-PAGE/immunoblotting and EAST
      inhibition experiments using sera of 15 green pea allergic individuals. The SDS
      PAGE/silver-staining experiments show the continuous change of protein pattern
      during maturation. SDS-PAGE/immunoblot and EAST inhibition demonstrate that all
      levels of green pea seeds show relevant IgE-binding capacity, as do immature
      seeds. Total IgE-binding capacity rises with the progress of maturation. Although
      the main allergenic activity is dependent upon the albumin fraction, the glutelin
      and globulin fractions are also important. The implication of these results is an
      obvious allergenic potency of all maturation levels, even immature seeds, whereas
      an increase of allergenicity during maturation could be notched up. The highest
      allergenic potency is caused by the albumin fraction, but globulin and glutelin
      fractions also contribute to the allergenicity of green pea.

PMID- 15740065
TI  - Identification of anthocyanins in Rhamnus alaternus L. berries.
AB  - Anthocyanin composition in berries of Rhamnus alaternus L., a perennial wild
      shrub typical of the Mediterranean area, was determined for the first time. The
      pigments were extracted from the berries with 0.1% HCl in methanol and purified
      using a C-18 solid-phase cartridge. High-performance liquid chromatography diode
      array detection-mass spectrometry analysis showed that delphinidin 3-O-rutinoside
      represented about 62.4% of the total pigments. Other anthocyanins were 3-O
      rutinoside derivatives of cyanidin (8.4%), petunidin (15.8%), pelargonidin
      (4.7%), and peonidin and malvidin (8.7%). The concomitant presence of the six
      most common anthocyanidins suggested that R. alaternus berries, besides being a
      good pigment source, could also be a useful tool for anthocyanin identification.

PMID- 15740066
TI  - Preparation and characterization of nanoparticles containing trypsin based on
      hydrophobically modified chitosan.
AB  - Trypsin was immobilized on linolenic acid modified chitosan using glutaraldehyde
      (GA) as cross-linker, which was confirmed by Fourier transform infrared (FTIR)
      spectra. The chitosan nanoparticles containing trypsin (TR) can be prepared after
      the sonication of immobilized trypsin. The GA concentration affected both the
      enzyme activity of the nanoparticle and particle size. Results indicated that the
      activity of trypsin immobilized onto linolenic acid modified chitosan
      nanoparticles increased with increasing concentration of GA up to 0.07% (v/v) and
      then decreased with increasing amount of GA. On the other hand, particle size
      increased (from 523 to 1372 nm) with the increasing concentration of GA (from
      0.03 to 0.1% v/v). The enzyme catalytic characteristics of nanoparticle solution
      were also studied. The results showed that the kinetic constant value (K(m)) of
      TR immobilized on nanoparticle (71.9 mg/mL) was higher than that of pure TR (50.2
      mg/mL). However, the thermal stability and optimum temperature of TR immobilized
      on nanoparticles improved, which make it more attractive in the application
      aspect.

PMID- 15740067
TI  - 11S and 7S globulins of coconut (Cocos nucifera L.): purification and
      characterization.
AB  - Total globulins extracted with 0.4 M NaCl in buffer from coconut endosperm
      separated into two peaks on gel filtration: peak I corresponding to 11S globulin
      or cocosin and peak II to 7S globulin with native molecular weights of 326 000
      and 156 000, respectively. The percent composition of total globulins was
      estimated to be 11S, 86% and 7S, 14%. On SDS-PAGE, cocosin resolved into two
      closely migrating bands at approximately 34 000 (acidic polypeptide) and another
      set of 2 bands at 24 000 (basic polypeptide). Each set consisted of one darkly
      stained band and one lightly stained band. The 7S globulin consisted of three
      bands of 16 000, 22 000, and 24 000. Three isoforms of cocosin were identified
      after anion exchange chromatography. Cocosin, but not the 7S, was found to have
      disulfide bonds. Using periodic acid-Schiff's reagent, all of the bands of
      cocosin on SDS-PAGE were positive for carbohydrate. However, when con A
      peroxidase was used, only the basic polypeptide stained positively for
      carbohydrate. For the 7S globulin, no carbohydrate group was detected using the
      PAS and con A-peroxidase tests. The 7S globulin was easily extracted with 0.10
      0.15 M NaCl, whereas cocosin was extracted with 0.35 M NaCl. The N-terminal amino
      acid sequences of the 34 k band and 24 k band of cocosin were SVRSVNEFRXE and
      GLEETQ, respectively, and that of the 7S was EQEDPELQK.

PMID- 15740068
TI  - Induction of apoptosis by the Anthocyanidins through regulation of Bcl-2 gene and
      activation of c-Jun N-terminal kinase cascade in hepatoma cells.
AB  - Anthocyanidins that are reddish pigments widely distributed in fruit and
      vegetables have been reported to possess antioxidant and anticancer activities.
      To understand the molecular basis of the putative anticancer activity of
      anthocyanidins, we investigated the antiproliferation effects of anthocyanidins
      in human hepatoma cell lines. Delphinidin, cyanidin, and malvidin exhibited
      strong growth inhibitory effects against human hepatoma HepG(2), but were less
      effective against Hep3B. According to the appearance of the caspase-3 fragments
      and stimulated proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) in
      time-dependent studies, delphinidin induced apoptotic cell death characterized by
      internucleosomal DNA fragmentation and caused a rapid induction of caspase-3
      activity. RT-PCR and Western blot data revealed that delphinidin stimulated an
      increase in the c-Jun and JNK phosphorylation expression at mRNA and protein
      levels, respectively. Moreover, delphinidin-induced apoptotic cell death was
      accompanied by up-regulation of Bax and down-regulation of Bcl-2 protein.
      Dephinidin-induced DNA fragmentation was blocked by N-acetyl-l-cysteine and
      catalase, suggesting that the death signaling was triggered by oxidative stress.
      Our experiments provide evidence that delphinidin is an effective apoptosis
      inducer in HepG(2) cells through regulation of Bcl-2 family moleculars and
      activation of c-Jun N-terminal kinase cascade. The results suggest that induction
      of apoptosis by anthocyanidins is a pivotal mechanism of their cancer
      chemopreventive functions.

PMID- 15740069
TI  - Antioxidant activity of the main phenolic compounds isolated from hot pepper
      fruit (Capsicum annuum L).
AB  - Four cultivars (Bronowicka Ostra, Cyklon, Tornado, and Tajfun) of pepper fruit
      Capsicum annuum L. were studied for phenolics contents and antioxidant activity.
      Two fractions of phenolics, flavonoids (with phenolic acids) and capsaicinoids,
      were isolated from the pericarp of pepper fruit at two growth stages (green and
      red) and were studied for their antioxidant capacity. Both fractions from red
      fruits had higher activities than those from green fruits. A comparison of the
      capsaicinoid fraction with the flavonoid and phenolic acid fraction from red
      fruit with respect to their antioxidant activity gave similar results. Phenolic
      compounds were separated and quantified by LC and HPLC. Contents of nine
      compounds were determined in the flavonoid and phenolic acid fraction: trans-p
      feruloyl-beta-d-glucopyranoside, trans-p-sinapoyl-beta-d-glucopyranoside,
      quercetin 3-O-alpha-l-rhamnopyranoside-7-O-beta-d-glucopyranoside, trans-p
      ferulyl alcohol-4-O-[6-(2-methyl-3-hydroxypropionyl] glucopyranoside, luteolin 6
      C-beta-d-glucopyranoside-8-C-alpha-l-arabinopyranoside, apigenin 6-C-beta-d
      glucopyranoside-8-C-alpha-l-arabinopyranoside, lutoeolin 7-O-[2-(beta-d
      apiofuranosyl)-beta-d-glucopyranoside], quercetin 3-O-alpha-l-rhamnopyranoside,
      and luteolin 7-O-[2-(beta-d-apiofuranosyl)-4-(beta-d-glucopyranosyl)-6-malonyl]
      beta-d-glucopyranoside. The main compounds of this fraction isolated from red
      pepper were sinapoyl and feruloyl glycosides, and the main compound from green
      pepper was quercetin-3-O-l-rhamnoside. Capsaicin and dihydrocapsaicin were the
      main components of the capsaicinoid fraction. A high correlation was found
      between the content of these compounds and the antioxidant activity of both
      fractions. Their antioxidant activities were elucidated by heat-induced oxidation
      in the beta-carotene-linoleic acid system and the antiradical activity by the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) decoloration test. The highest antioxidant
      activity in the beta-carotene-linoleic acid system was found for trans-p-sinapoyl
      beta-d-glucopyranoside, which was lower than the activity of free sinapic acid.
      Quercetin 3-O-alpha-l-rhamnopyranoside had the highest antiradical activity in
      the DPPH system, which was comparable to the activity of quercetin. The
      activities of capsaicin and dihydrocapsaicin were similar to that of trans-p
      feruloyl-beta-d-glucopyranoside in the DPPH model system.

PMID- 15740070
TI  - ATR-FT/IR study on the interactions between gliadins and dextrin and their
      effects on protein secondary structure.
AB  - The effects of heat treatment and dextrin addition on the secondary structure of
      gliadins were investigated by means of attenuated total reflection Fourier
      transform infrared spectroscopy (ATR-FT/IR). Gliadins and gliadin/dextrin
      mixtures (before and after thermal treatment) were prepared as a dried protein
      film on the ATR-FT/IR zinc selenide cell plate and equilibrated at a water
      activity (a(w)) of 0.06. The results show that gliadins undergo conformational
      changes upon thermal treatment both in the absence and in the presence of
      dextrin. In particular, in the thermally treated gliadins, the decrease of the
      band at around 1651 cm(-)(1) and the increase of the bands at around 1628 and
      1690 cm(-)(1) suggest a loss of alpha-helix structure and a higher content of
      protein aggregates. The same trend was observed in the presence of dextrin.
      Concerning the interactions between gliadins and dextrin, gliadin/dextrin
      mixtures show variations in the amide I region compared to native gliadins (e.g.,
      an increase of the band at 1645 cm(-)(1) and the absence of the band at around
      1668 cm(-)(1)) that might be due to hydrogen bond formation between gliadins and
      dextrin. It was also found that the spectrum of gliadin/dextrin mixtures was less
      affected by the hydration state than that of native gliadins, as observed from
      the differential spectra obtained by subtraction of the spectrum obtained at a(w)
      = 0.06 (driest condition tested) from the spectrum of the sample equilibrated at
      a(w) = 0.84. This could be due to the fact that C=O and N-H groups of gliadins
      are engaged to form hydrogen bonds with the hydroxyl groups of dextrin, and so
      they are not perturbed by the presence of water molecules. Finally, water
      activity effects on the secondary structure of gliadins are also discussed.

PMID- 15740071
TI  - Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids.
AB  - Inhibition of acetylcholinesterase (AChE) activity by 17 kinds of bicyclic
      monoterpenoids was investigated. Bicyclic monoterpenoids are contained in many
      kinds of essential oils. Inhibition of AChE was measured according to the
      colorimetric method. 3.1.1 and 4.1.0 bicyclic hydrocarbons with allylic methyl
      group showed strong inhibition. (+)- and (-)-alpha-pinene and (+)-3-carene were
      potent inhibitors of AChE. 3.1.1 and 2.2.1 bicyclic alcohols and ketones showed
      weak inhibition. 3.1.1 and 4.1.0 bicyclic hydrocarbons with allylic methyl group
      were found to be uncompetitive inhibitors.

PMID- 15740072
TI  - Structure-function analysis of the vanillin molecule and its antifungal
      properties.
AB  - The aim of the present study was to evaluate which structural elements of the
      vanillin molecule are responsible for its observed antifungal activity. MICs of
      vanillin, its six direct structural analogues, and several other related
      compounds were determined in yeast extract peptone dextrose broth against a total
      of 18 different food spoilage molds and yeasts. Using total mean MICs after 4
      days of incubation at 25 degrees C, the antifungal activity order was 3
      anisaldehyde (1.97 mM) > benzaldehyde (3.30 mM) > vanillin (5.71 mM) > anisole
      (6.59 mM) > 4-hydroxybenzaldehyde (9.09 mM) > phenol (10.59 mM) > guaiacol (11.66
      mM). No correlation was observed between the relative antifungal activity of the
      test compounds and log P(o/w). Furthermore, phenol (10.6 mM) was found to exhibit
      a greater activity than cyclohexanol (25.3 mM), whereas cyclohexanecarboxaldehyde
      (2.13 mM) was more active than benzaldehyde (3.30 mM). Finally, the antifungal
      order of isomers of hydroxybenzaldehyde and anisaldehyde was found to be 2- > 3-
      > 4- and 3- > 2- > 4-, respectively. In conclusion, the aldehyde moeity of
      vanillin plays a key role in its antifungal activity, but side-group position on
      the benzene ring also influences this activity. Understanding how the structure
      of natural compounds relates to their antimicrobial function is fundamentally
      important and may help facilitate their application as novel food preservatives.

PMID- 15740073
TI  - Induction of apoptosis by three marine algae through generation of reactive
      oxygen species in human leukemic cell lines.
AB  - In this study, we examined the antitumor effect of marine algae extracts on human
      hepatoma and leukemia cells. Ethyl acetate extracts from Colpomenia sinuosa (Cs
      EA), Halimeda discoidae (Hd-EA), and Galaxaura oblongata (Go-EA) directly
      inhibited the growth of human hepatoma HuH-7 cells and leukemia U937 and HL-60
      cells in a time- and dose-dependent manner. Specifically, these algae extracts
      induced apoptosis of U937 and HL-60 cells as evaluated by detection of
      hypodiploid cells using flow cytometry and observation of condensed and
      fragmented nuclei in algae extract-treated cells. Intracellular reactive oxygen
      species (ROS), especially hydrogen peroxide and superoxide anion, were increased
      about 2-3-fold in U937 cells treated with Cs-EA for 3-5 h. Interestingly,
      antioxidant N-acetylcysteine effectively blocked Cs-EA-, Hd-EA-, and Go-EA
      induced apoptosis, suggesting that ROS is a key mediator in the apoptotic
      signaling pathway. In conclusion, our results show that algae extracts induce
      apoptosis in human leukemia cells through generation of ROS.

PMID- 15740074
TI  - Degradation of neohesperidin dihydrochalcone by human intestinal bacteria.
AB  - The degradation of neohesperidin dihydrochalcone by human intestinal microbiota
      was studied in vitro. Human fecal slurries converted neohesperidin
      dihydrochalcone anoxically to 3-(3-hydroxy-4-methoxyphenyl)propionic acid or 3
      (3,4-dihydroxyphenyl)propionic acid. Two transient intermediates were identified
      as hesperetin dihydrochalcone 4'-beta-d-glucoside and hesperetin dihydrochalcone.
      These metabolites suggest that neohesperidin dihydrochalcone is first
      deglycosylated to hesperetin dihydrochalcone 4'-beta-d-glucoside and subsequently
      to the aglycon hesperetin dihydrochalcone. The latter is hydrolyzed to the
      corresponding 3-(3-hydroxy-4-methoxyphenyl)propionic acid and probably
      phloroglucinol. Eubacterium ramulus and Clostridium orbiscindens were not capable
      of converting neohesperidin dihydrochalcone. However, hesperetin dihydrochalcone
      4'-beta-d-glucoside was converted by E. ramulus to hesperetin dihydrochalcone and
      further to 3-(3-hydroxy-4-methoxyphenyl)propionic acid, but not by C.
      orbiscindens. In contrast, hesperetin dihydrochalcone was cleaved to 3-(3-hydroxy
      4-methoxyphenyl)propionic acid by both species. The latter reaction was shown to
      be catalyzed by the phloretin hydrolase from E. ramulus.

PMID- 15740075
TI  - Isolation and characterization of enzymes involved in lysine catabolism from
      sorghum seeds.
AB  - Lysine is an essential amino acid synthesized in plants via the aspartic acid
      pathway. The catabolism of lysine is performed by the action of two consecutive
      enzymes, lysine 2-oxoglutarate reductase (LOR, EC 1.5.1.8) and saccharopine
      dehydrogenase (SDH, EC 1.5.1.9). The final soluble lysine concentration in cereal
      seeds is controlled by both synthesis and catabolism rates. The production and
      characterization of high-lysine plants species depends on knowledge of the
      regulatory aspects of lysine metabolism and manipulation of the key enzymes. We
      have for the first time isolated, partially purified, and characterized LOR and
      SDH from developing sorghum seeds, which exhibited low levels of activity. LOR
      and SDH were only located in the endosperm and were very unstable during the
      isolation and purification procedures. LOR and SDH exhibited some distinct
      properties when compared to the enzymes isolated from other plant species,
      including a low salt concentration required to elute the enzymes during anion
      exchange chromatography and the presence of multimeric forms with distinct
      molecular masses.

PMID- 15740076
TI  - Yield and composition of grape seed oils extracted by supercritical carbon
      dioxide and petroleum ether: varietal effects.
AB  - Grape seed has a well-known potential for production of oil as a byproduct of
      winemaking and is currently produced as a specialty oil byproduct of wine
      manufacture. Seed oils from eight varieties of grapes crushed for wine production
      in British Columbia were extracted by supercritical carbon dioxide (SCE) and
      petroleum ether (PE). Oil yields by SCE ranged from 5.85 +/- 0.33 to 13.6 +/-
      0.46% (w/w), whereas PE yields ranged from 6.64 +/- 0.16 to 11.17 +/- 0.05% (+/-
      is standard deviation). The oils contained alpha-, beta-, and gamma-tocopherols
      and alpha- and gamma-tocotrienols, with gamma-tocotrienol being most important
      quantitatively. In both SCE- and PE-extracted oils, phytosterols were a prominent
      feature of the unsaponifiable fraction, with beta-sitosterol quantitatively most
      important with both extractants. Total phytosterol extraction was higher with SCE
      than with PE in seven of eight variety extractions. Fatty acid composition of
      oils from all varieties tested, and from both extraction methods, indicated
      linoleic acid as the major component ranging from 67.56 to 73.23% of the fatty
      acids present, in agreement with literature reports.

PMID- 15740077
TI  - Two types of radicals in whole milk powder. Effect of lactose crystallization,
      lipid oxidation, and browning reactions.
AB  - Whole milk powder was stored in closed vials at 60 degrees C to induce
      crystallization of lactose within a short time scale. After an induction period
      of 3-4 days simultaneous crystallization of lactose, increase of water activity,
      formation of browning products, and increase of radical content took place.
      Radicals detected before lactose crystallization were characterized by a narrow
      ESR spectrum (g = 2.006) and could be depleted by removal of oxygen and therefore
      were assigned to oxidation processes. Late-stage radicals present after
      crystallization of lactose gave much wider spectra (g = 2.0048) and were
      independent of oxygen availability and assigned to late-stage Maillard reaction
      products. The study indicates that the processes of lactose crystallization,
      browning, and formation of radical species (g = 2.0048) are strongly coupled,
      while lipid oxidation is less dependent on the other processes.

PMID- 15740078
TI  - Flavones suppress the expression of the high-affinity IgE receptor FcepsilonRI in
      human basophilic KU812 cells.
AB  - We examined the effect of flavones on the expression of the high-affinity IgE
      receptor FcepsilonRI, which plays a central role in the IgE-mediated allergic
      response. Flow cytometric analysis showed that the flavones chrysin and apigenin
      were able to reduce the cell surface expression of FcepsilonRI in human
      basophilic KU812 cells. Immunoblot analysis revealed that the total cellular
      expression of the FcepsilonRI alpha and gamma chains decreased upon treatment
      with chrysin and apigenin. Moreover, the level of mRNA expression of the
      FcepsilonRI alpha and gamma chains also decreased when the cells were cultured
      with the two flavones. Previously, we demonstrated that the reduction of
      extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation was involved in
      the downregulation of FcepsilonRI expression. The two flavones were shown to
      reduce the level of ERK1/2 phosphorylation. These results suggested that chrysin
      and apigenin have the ability to downregulate FcepsilonRI expression and this
      suppressive effect may be due to the reduction of ERK1/2 phosphorylation.

PMID- 15740079
TI  - Effect of EDTA alone and in combination with polygodial on the growth of
      Saccharomyces cerevisiae.
AB  - The antifungal activity of ethylenediaminetetraacetic acid (EDTA) against
      Saccharomyces cerevisiae was significantly affected by various conditions such as
      inoculum size, pH, and metal ions (Mg(2+), Ca(2+)). EDTA was found to be
      effective against this yeast at the inoculum size of 10(5) colony forming units
      (CFU)/mL with the minimum inhibitory concentration of 400 mug/mL and the minimum
      fungicidal concentration of 6400 mug/mL, but it was not effective at 10(7) CFU/mL
      up to 6400 mug/mL. The fungicidal activity of EDTA against S. cerevisiae was
      significantly enhanced in combination with polygodial. Isobolograms, fractional
      inhibitory concentration, and fractional fungicidal concentration indices were
      used for evaluating the interaction between combined compounds. This synergistic
      effect is likely due to polygodial's destructive action on the cellular membrane,
      which facilitates the transmembrane transport of foreign compounds (EDTA) into
      yeast cells. Once inside the cells, EDTA forms chelation with divalent metals
      such as Mg(2+) and Ca(2+), which are required by various essential enzymes.

PMID- 15740080
TI  - Inhibitory effects of feeding with carrots or (-)-falcarinol on development of
      azoxymethane-induced preneoplastic lesions in the rat colon.
AB  - The effects of intake of dietary amounts of carrot or corresponding amounts of (
      )-(3R)-falcarinol from carrots on development of azoxymethane (AOM)-induced colon
      preneoplastic lesions were examined in male BDIX rats. Three groups of eight AOM
      treated rats were fed the standard rat feed Altromin supplemented with either 10%
      (w/w) freeze-dried carrots with a natural content of 35 mug falcarinol/g, 10%
      maize starch to which was added 35 mug falcarinol/g purified from carrots, or 10%
      maize starch (control). After 18 weeks, the animals were euthanized and the colon
      was examined for tumors and aberrant crypt foci (ACF), which were classified into
      four size classes. Although the number of small ACF was unaffected by the feeding
      treatments, the numbers of lesions as a function of increasing size class
      decreased significantly in the rats that received one of the two experimental
      treatments, as compared with the control treatment. This indicates that the
      dietary treatments with carrot and falcarinol delayed or retarded the development
      of large ACF and tumors. The present study provides a new perspective on the
      known epidemiological associations between high intake of carrots and reduced
      incidence of cancers.

PMID- 15740081
TI  - Grapefruit and oroblanco enhance hepatic detoxification enzymes in rats: possible
      role in protection against chemical carcinogenesis.
AB  - Citrus fruits are considered to be functional foods that promote good health.
      This study was carried out to assess the effect of oroblanco and grapefruit
      consumption on hepatic detoxification enzymes. Male Sprague-Dawley rats were
      provided with either regular drinking water (control) or experimental treatments
      of oroblanco juice, grapefruit juice, or a sugar mix for 6 weeks. After 1 week of
      treatment, half the animals in each group were injected with the procarcinogen
      1,2-dimethylhydrazine. Grapefruit juice significantly increased activity and
      expression of the hepatic phase I enzyme, cytochrome P450 CYP1A1, with a marked
      trend toward enhanced NAD(P)H:quinone reductase (QR) activity. Oroblanco juice
      significantly increased glutathione S-transferase phase II enzyme activity along
      with CYP1A1 expression and a notable trend toward increased activity of both
      CYP1A1 and QR. These results suggest that these citrus fruits are bifunctional
      inducers, modulating both phase I and phase II drug-metabolizing enzymes to
      enhance hepatic detoxification.

PMID- 15740082
TI  - Secondary metabolite and mycotoxin production by the Rhizopus microsporus group.
AB  - Fast-growing Zygomycetes, most notably Rhizopus oligosporus, are traditionally
      used in many food fermentations, for example, for soybean tempeh production. R.
      oligosporus is considered to belong to the Rhizopus microsporus group. Certain R.
      microsporus strains have been reported to produce either the pharmaceutically
      active rhizoxins or the highly toxic rhizonins A and B. In this study was
      investigated the formation of secondary metabolites by R. microsporus, R.
      oligosporus, and Rhizopus chinensis grown on a wide range of different
      semisynthetic and natural substrates. Liquid chromatography, combined with
      photodiode array detection and high-resolution mass spectrometric techniques, was
      used to identify secondary metabolites. Growth on maize, brown rice, and Pharma
      agar gave both the highest amounts and the maximum diversity of rhizoxins and
      rhizonins. Rhizoxins were produced by all four R. microsporus strains, whereas
      only one strain produced rhizonins. The six R. oligosporus and four R. chinensis
      strains investigated did not produce any of these two classes of metabolites.

PMID- 15740083
TI  - Discovery of and mechanistic insight into a ligand-modulated palladium-catalyzed
      Wacker oxidation of styrenes using TBHP.
AB  - We describe the discovery of a new N-heterocyclic carbene-modulated Pd catalyst
      for the Wacker oxidation that does not require molecular oxygen but instead uses
      TBHP as a reagent in this oxidation. The catalyst activity and selectivity for
      the oxidation of styrene derivatives to methyl ketones are among the best
      reported. Preliminary mechanistic studies of the catalytic system were performed
      and show that the origin of the carbonyl oxygen is TBHP and that the hydrogens in
      the product all originate from the starting olefin.

PMID- 15740084
TI  - Endohedral clusterization of ten water molecules into a "molecular ice"within the
      hydrophobic pocket of a self-assembled cage.
AB  - An adamantanoid (H2O)10 cluster is formed within the hydrophobic cavity of a self
      assembled coordination cage. This cluster is termed "molecular ice" because it is
      the smallest unit of naturally occurring Ic-type ice. X-ray structural analysis,
      coupled with neutron diffraction study, reveals that the molecular ice is formed
      not by a simple space-filling effect but by efficient molecular recognition
      within the cage via H2O:...pi interaction.

PMID- 15740085
TI  - A self-assembling protein template for constrained synthesis and patterning of
      nanoparticle arrays.
AB  - Self-assembling biomolecules that form highly ordered structures have attracted
      interest as potential alternatives to conventional lithographic processes for
      patterning materials. Here, we introduce a general technique for patterning
      nanoparticle arrays using two-dimensional crystals of genetically modified hollow
      protein structures called chaperonins. Constrained chemical synthesis of
      transition metal nanoparticles is initiated using templates functionalized with
      polyhistidine sequences. These nanoparticles are ordered into arrays because the
      template-driven synthesis is constrained by the nanoscale structure of the
      crystallized protein. We anticipate that this system may be used to pattern
      different classes of nanoparticles based on the growing library of sequences
      shown to specifically bind or direct the growth of materials.

PMID- 15740087
TI  - A self-assembled nano optical switch and transistor based on a rigid conjugated
      polymer, thioacetyl-end-functionalized poly(para-phenylene ethynylene).
AB  - A nanometer-scale optical switch and transistor were fabricated with thioacetyl
      end-functionalized poly(para-phenylene ethynylene)s and Au nanogap electrodes by
      self-assembly. With photoirradiation, the switch can be switched on/off quickly
      with a switching ratio as high as 1000. Moreover, the device works well as a p
      type transistor. With an increase in gate bias, strong conductance oscillation
      was observed in this self-assembled transistor (under low temperature 147 K),
      which is very likely due to single-electron charging oscillations arising from
      electron tunneling through the nanometer-scale transistor.

PMID- 15740086
TI  - An in vitro selection system for TNA.
AB  - (3'-2')-alpha-l-Threose nucleic acid (TNA) is an unnatural polymer that possesses
      the rare ability to base-pair with RNA, DNA, and itself. This feature, coupled
      with its chemical simplicity, makes TNA of interest as a possible progenitor of
      RNA during the early history of life. To evaluate the functional potential of
      TNA, we have developed a system for the in vitro selection of TNA. We identified
      the Therminator DNA polymerase as a remarkably efficient DNA-dependent TNA
      polymerase capable of polymerizing more than 50 tNTPs. We have also developed a
      method of covalently linking a DNA template to the TNA strand that it encodes,
      thus obviating the need for a TNA-dependent DNA polymerase during cycles of
      selection.

PMID- 15740088
TI  - Selective detection of 2-deoxyribonolactone in DNA.
AB  - 2-Deoxyribonolactone (L) is an oxidized abasic lesion that is produced by a
      variety of DNA damaging agents. It exhibits unique biological effects with
      respect to its proclivity to form DNA-protein cross-links and promutagenic base
      pairs. Recent evidence suggests that the levels of this lesion caused by
      oxidative stress are underestimated. We have developed a simple, selective method
      for detecting subpicomole amounts of L in DNA. The method takes advantage of the
      selective reaction of the butenolide (2) derived from beta-elimination from L
      with a biotinylated derivative of cysteine. This method will be useful for
      analyzing the levels of this oxidized abasic site in DNA.

PMID- 15740089
TI  - Deblurred observation of the molecular structure of an oil-water interface.
AB  - We simulated the interface between liquid water and a stationary phase of
      tethered n-C18 alkyl chains at a thermodynamic state of low pressure and water
      vapor-liquid coexistence. The interfacial water (oxygen atom) density profile so
      obtained is compared with a precisely defined proximal density of water molecules
      (oxygen atoms) conditional on the alkyl chain configurations. Though the
      conventional interfacial density profile takes a traditional monotonic form, the
      proximal radial distribution of oxygen atoms around a specific methyl (methylene)
      group closely resembles that for a solitary methane solute in liquid water.
      Moreover, this proximal radial distribution function is sufficient to accurately
      reconstruct the water oxygen density profile of the oil-water interface. These
      observations provide an alternative interpretation to collective drying or
      vaporization interpretations of commonly observed oil-water interfacial profiles
      for which water penetration into the interfacial region plays a role.

PMID- 15740091
TI  - Structure and magnetism of VnBz(n+1) sandwich clusters.
AB  - Results on structural, energetic, electronic, and magnetic properties of linear
      sandwich VnBzn+1 clusters obtained using high-accuracy density functional
      computations are presented and analyzed. Energetically close-lying configurations
      and states of different spin-multiplicities are identified. The computed
      characteristics are in good agreement with the available experimental data. The
      computations predict that the most stable forms of the clusters in the size range
      n >/= 4 are chiral. This feature, combined with the magnetism of these systems,
      makes them of potential importance as building blocks of nanosystems with coupled
      optical and magnetic functionalities.

PMID- 15740090
TI  - PEGylated polyplex micelles from triblock catiomers with spatially ordered
      layering of condensed pDNA and buffering units for enhanced intracellular gene
      delivery.
AB  - An A-B-C type triblock copolymer, tandemly aligning two types of polycations with
      different pKa values in a single polymer strand, was developed for the
      construction of novel polyplex micelles, satisfying a high DNA condensing ability
      as well as a proton buffering activity directed to elevating gene transfection.
      The micelle might feature the distinctive three-layered structure, where an inner
      polyplex layer of condensed pDNA with poly(l-lysine) (pKa approximately 9.4) as
      the C segment is successively wrapped with an intermediate layer of poly[(3
      morpholinopropyl)aspartamide] (B segment) with a comparatively low pKa of
      approximately 6.2, to provide a buffering effect, and an outer PEG layer (A
      segment) as a biocompatible palisade.

PMID- 15740092
TI  - Calcium oxalate monohydrate precipitation at membrane lipid rafts.
AB  - The precipitation of calcium oxalate monohydrate (COM) was monitored at a
      Langmuir monolayer containing lipid raft domains. The raft-forming monolayer
      consists of a 2:1:1 mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine/sphingomyelin/dihydrocholesterol, where the raft liquid ordered
      phase is enriched in sphingomyelin and the sterol. COM crystals, monitored by
      Brewster angle microscopy, appear at the phase boundary between the raft domains
      and the expanded phase.

PMID- 15740093
TI  - Patterns formed by droplet evaporation from a restricted geometry.
AB  - We show that hundreds of concentric rings, each approximately nanometers high and
      micrometers wide, form when a drop is allowed to evaporate from a confined
      geometry, leaving behind a dry, nonvolatile polymer solute. This new preparative
      strategy offers a simple, versatile, generalizable method to produce patterns of
      unprecedented high fidelity and regularity, as well as a direction to look to
      design yet more complex patterns.

PMID- 15740094
TI  - The dichotomy of dimetallocenes: coaxial versus perpendicular dimetal units in
      sandwich compounds.
AB  - Theoretical studies of the dimetallocene (eta5-C5H5)2Zn2 lead to optimized D5h or
      D5d structures in which the Zn-Zn bond is coaxial with the C5 axes of the two Cp
      rings, with a Zn-Zn distance of 2.33 A, corresponding to a Zn-Zn single bond.
      (eta5-C5H5)2Ni2 (singlet state) and (eta5-C5H5)2Cu2 (triplet) have similar
      structures with a NiNi triple bond (2.06 A) and a Cu=Cu double bond (2.22 A).
      However, DFT computations on (C5H5)2Ni2 and (C5H5)2Cu2 (both singlet states) lead
      to a totally different type of optimized structure (Ci symmetry) lying at
      significantly lower energies, with the metal-metal bonds perpendicular to the C5
      axes of the Cp rings.

PMID- 15740095
TI  - Molecular sensing with ultrafine silver crystals on hexagonal aluminum nitride
      nanorod templates.
AB  - A fully plasma-based technique of generating ultrafine (sub-10-nm)
      nanocrystalline silver particulates on wide band gap and chemically inert
      hexagonal aluminum nitride nanorod templates has been demonstrated. These
      specially prepared substrates are ready to use for molecular sensing by room
      temperature surface-enhanced Raman scattering. An enhancement factor of 2 x 106
      was observed for micromolar solutions of Rhodamine 6G.

PMID- 15740096
TI  - Large-scale fabrication of flexible silver/cross-linked poly(vinyl alcohol)
      coaxial nanocables by a facile solution approach.
AB  - A new method to prepare flexible Ag/cross-linked poly(vinyl alcohol) (PVA)
      nanocables has been discovered for the first time by one-step in situ reduction
      of Ag+ and Ag+-catalyzed cross-linking of PVA chains under hydrothermal
      conditions.

PMID- 15740097
TI  - Allele-specific inhibitors of protein tyrosine phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) are critical cell-signaling molecules.
      Inhibitors that are selective for individual PTPs would be valuable tools for
      dissecting complicated phosphorylation networks. However, the common architecture
      of PTP active sites impedes the discovery of such compounds. To achieve target
      selectivity, we have redesigned a PTP/inhibitor interface. Site-directed
      mutagenesis of a prototypical phosphatase, PTP1B, was used to generate "inhibitor
      sensitized" PTPs. The PTP1B mutants were targeted by modifying a broad
      specificity PTP inhibitor with chemical groups that are sterically incompatible
      with wild-type PTP active sites. From a small panel of putative inhibitors,
      compounds that selectively inhibit Ile219Ala PTP1B over the wild-type enzyme were
      identified. Importantly, the corresponding mutation also conferred novel
      inhibitor sensitivity to T-cell PTP, suggesting that a readily identifiable point
      mutation can be used to generate a variety of inhibitor-sensitive PTPs.

PMID- 15740098
TI  - Lipid mobility and molecular binding in fluid lipid membranes.
AB  - The lateral mobility of dilute concentrations of fluorescently labeled lipids
      doped into supported membranes is found to change upon receptor ligand binding at
      the membrane surface, even when the lipid is not directly involved in the binding
      event. Experiments using membrane microarrays are performed that illustrate the
      use of lipid mobility measurements as an effectively label-free strategy of
      detecting binding on membrane surfaces.

PMID- 15740099
TI  - DNA-templated three-branched nanostructures for nanoelectronic devices.
AB  - Three-branched DNA molecules have been designed and assembled from
      oligonucleotide components. These nucleic acid constructs contain double- and
      single-stranded regions that control the hybridization behavior of the assembly.
      Specific localization of a single streptavidin molecule at the center of the DNA
      complex has been investigated as a model system for the directed placement of
      nanostructures. Highly selective silver and copper metallization of the DNA
      template has also been characterized. Specific hybridization of these DNA
      complexes to oligonucleotide-coupled nanostructures followed by metallization
      should provide a bottom-up self-assembly route for the fabrication and
      characterization of discrete three-terminal nanodevices.

PMID- 15740100
TI  - Temperature dependence of carbon-13 kinetic isotope effects of importance to
      global climate change.
AB  - We report here a theoretical study of the 13C kinetic isotope effect (KIE) and
      its temperature dependence for the reaction OH + CH4 --> H2O + CH3, the major
      sink of atmospheric methane in the troposphere. The KIE values at various
      atmospherically significant temperatures were determined by direct dynamics using
      variational transition state theory with multidimensional tunneling contributions
      (VTST/MT). The potential energy surfaces (PESs) were generated by hybrid density
      functional theory as well as by recently developed doubly hybrid density
      functional theory methods. Comparisons of our calculated KIEs with experimental
      data and theoretical values in the literature reveal the critical contributions
      due to multidimensional tunneling and torsion anharmonicity as well as the
      critical issue of the choice of internal rotational axis.

PMID- 15740101
TI  - Alkane oxidation by osmium tetroxide.
AB  - Aqueous alkaline OsO4 at 85 degrees C oxidizes saturated alkanes, including
      primary, secondary, and tertiary C-H bonds. Isobutane affords tert-butanol in
      quantitative yield based on consumed OsO4. Cyclohexane is oxidized to a mixture
      of adipate and succinate. Ethane and propane are oxidized to acetate, which
      itself is further oxidized under the reaction conditions. A few turnovers of
      isobutane oxidation have been accomplished using NaIO4 as the terminal oxidant.
      The alkane oxidation is an example of ligand accelerated catalysis, as hydroxide
      binding to OsO4 is required for reaction. A concerted mechanism involving [3+2]
      addition of a C-H bond to two oxo groups of OsO4(OH)- is suggested, analogous to
      the pathways for dihydroxylation of alkenes by OsO4(L) and for addition of H2 to
      OsO4(L).

PMID- 15740102
TI  - Imaging chirality with surface second harmonic generation microscopy.
AB  - Chirality is a fundamental construct in nature which arises from an antisymmetric
      arrangement of atoms, molecules, or larger structures, resulting in the formation
      of nonsuperimposable mirror images. Bulk chiral effects can easily be measured
      using circular dichroism (CD) or optical rotary dispersion (ORD). However, the
      imaging of chirality originating from molecular surface films cannot be obtained
      with these linear optical methods. By using chiral second harmonic generation (C
      SHG), with its inherent surface sensitivity and ability to discriminate between
      the symmetry of surface adsorbed species in combination with a counter
      propagating optical geometry, we have developed the first nonlinear chiral
      microscope. In the study presented here, the intrinsic chirality of R- and S-(+)
      1,1'-bi-2-naphthol (RBN, SBN) has been used to image a patterned planar supported
      lipid bilayer (PSLB) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      using C-SHG. Spatial resolution of the patterned PSLB is visible when either RBN
      or SBN is intercalated into the membrane. No image is observed when a racemic
      mixture of RBN and SBN is present. The C-SHG images are compared with those
      obtained from fluorescence microscopy to verify the C-SHG imaging technique. The
      results presented here demonstrate that C-SHG possesses the requisite surface
      selectivity and sensitivity to detect interfacial chirality and provides a direct
      route for the visualization of chirality originating from molecular surface
      films.

PMID- 15740103
TI  - Multicomponent cycloadditions: the four-component [5+1+2+1] cycloaddition of
      vinylcyclopropanes, alkynes, and CO.
AB  - Prompted by the view that intermediates of transition metal-catalyzed reactions
      could be intercepted by one or more additional components, studies in our
      laboratory have led to the design and development of new three-component [5+2+1],
      [4+2+1], and [2+2+1] cycloadditions. These continuing studies have now led to the
      identification of a fundamentally new four-component [5+1+2+1] cycloaddition
      reaction of vinylcyclopropanes, alkynes and CO, yielding hydroxyindanone products
      in generally good yields. Terminal alkynes bearing aryl or alkyl groups are
      tolerated well. Substitution at any position of the VCP leads predictably to
      substituted hydroxyindanone products. Using a bis-alkynyl substrate, the reaction
      can be carried out bi-directionally, forming 10 C-C bonds and four new rings from
      seven components in a single, operationally simple process.

PMID- 15740104
TI  - All-catalytic, efficient, and asymmetric synthesis of alpha,omega
      diheterofunctional reduced polypropionates via "one-pot" Zr-catalyzed asymmetric
      carboalumination-Pd-catalyzed cross-coupling tandem process.
AB  - A highly efficient method for the synthesis of stereochemically pure (>/=99% ee
      and >50/1 dr) alpha,omega-diheterofunctional reduced polypropionates has been
      developed. The essential features of the method are represented by the conversion
      of inexpensive styrene into 2-methyl-4-phenyl-1-pentanol (1) in 50% yield over
      two steps from styrene via Zr-catalyzed asymmetric carboalumination (ZACA)
      reaction in the presence of (NMI)2ZrCl2 and Pd-catalyzed vinylation of the in
      situ generated isoalkylalanes in the presence of Zn(OTf)2 and a catalytic amount
      of Pd(DPEphos)Cl2. This ZACA-Pd-catalyzed vinylation may be repeated as needed
      without purification. After the final ZACA reaction, oxidation with O2 provides
      alpha-hydroxy-omega-phenyl reduced polypropionates, which can be fully or
      partially purified by chromatography. After acetylation, Ru-catalyzed oxidative
      cleavage of the Ph ring, and reduction with BH3.THF, the second chromatographic
      purification provides stereoisomerically pure alpha,omega-diheterofunctional
      reduced polypropionates (e.g., 9 and 11) that can be further converted to key
      intermediates 6 and 7 for the synthesis of ionomycin (4) and borrelidin (5),
      respectively, by known reactions.

PMID- 15740105
TI  - UV raman examination of alpha-helical peptide water hydrogen bonding.
AB  - UV resonance Raman spectra (UVRS) of an alpha-helical, 21 residue, mainly Ala
      peptide (AP) in the dehydrated solid state were compared to those in aqueous
      solution at different temperatures. The UVRS amide band frequencies of a
      dehydrated solid alpha-helix peptide show frequency shifts compared to those in
      aqueous solution due to the loss of amide backbone hydrogen bonding to water; the
      amide II and amide III bands of the solid alpha-helix downshift, while the amide
      I band upshifts. The shifts are identical in direction but smaller than those
      that occur for alpha-helices in aqueous solution as the temperature increases;
      water hydrogen bonding strengths decrease as the temperature increases. The UV
      Raman amide band frequency shifts can be used to monitor alpha-helix hydrogen
      bonding.

PMID- 15740106
TI  - Highly selective 1,3-isomerization of allylic alcohols via rhenium oxo catalysis.
AB  - Two reaction strategies are developed to promote the highly selective 1,3
      isomerization of a variety of allylic alcohols using O3ReOSiPh3 as a catalyst.
      The first strategy utilizes substrates whose 1,3-regioisomer contains a
      conjugated alkene, which relies on thermodynamics to obtain high selectivity. The
      second strategy employs N,O-bis(trimethylsilyl)acetamide as an additive to
      selectively and irreversibly remove the product from the reaction equilibrium and
      works well for the isomerization of tertiary allylic alcohols into primary
      allylic alcohols containing trisubstituted alkene components. High
      stereoselectivity is also observed in the 1,3-isomerization of enantioenriched
      allylic alcohols.

PMID- 15740107
TI  - Total synthesis of (+)-allocyathin B2.
AB  - The first enantioselective synthesis of (+)-allocyathin was achieved. The
      synthesis features a Pd-catalyzed asymmetric allylic alkylation to install the
      first quaternary center, a Ru-catalyzed diastereoselective cycloisomerization to
      construct the six-membered ring, and a diastereoselective hydroxylative
      Knoevenagel reaction to introduce the final hydroxyl group. The unusual olefin
      isomerization of the Ru-catalyzed cycloisomerization was discussed and exploited
      for the synthesis.

PMID- 15740108
TI  - Regio- and enantioselective Pd-catalyzed allylic alkylation of ketones through
      allyl enol carbonates.
AB  - The Pd-catalyzed reorganization of enol allyl carbonates to allylated ketones
      occurs asymmetrically in the presence of chiral ligands previously developed in
      this group. With 2-methylcyclohexanone, asymmetric regioselective alkylation
      occurs at the more substituted carbon without complications of polyalkylation.
      Alkylation to create quaternary centers in indanones and benzonabenone occurs in
      much higher ee than using tin or lithium enolates. The sense of enantioinduction
      in tetralones is opposite from the tin and lithium enolate examples. For the
      first time, asymmetric creation of tertiary centers occurs with high ee (78-99%).
      The different results between this reaction and the use of lithium or tin
      enolates suggest different mechanisms may be involved.

PMID- 15740109
TI  - Development of an electrolytic system using solid-supported bases for in situ
      generation of a supporting electrolyte from methanol as a solvent.
AB  - We have successfully developed a novel electrolytic system using solid-supported
      bases for in situ generation of a supporting electrolyte from methanol as a
      solvent. Anodic methoxylation of phenyl 2,2,2-trifluoroethyl sulfide using solid
      supported bases was carried out to provide the alpha-methoxylated product in good
      to excellent yields. The alpha-methoxylated product and solid-supported bases
      were easily separated by only filtration, and the separated solid-supported bases
      were recyclable. Anodic methoxylation of phenyl 2,2,2-trifluoroethyl sulfide was
      successfully carried out 10 times by the recycling of silica gel-supported
      piperidine in good yields.

PMID- 15740110
TI  - Alternating isotactic ethylene-cyclopentene copolymer: a crystalline engineering
      plastomer including high amounts of structural disorder.
AB  - Crystals of alternating isotactic ethylene-cyclopentene copolymer include
      conformational disorder of cyclopentene rings and packing disorder of chains.

PMID- 15740111
TI  - Room-temperature catalytic hydrodefluorination of C(sp3)-F bonds.
AB  - Room-temperature catalytic hydrodefluorination of the strong C(sp3)-F bonds in
      benzotrifluorides and fluoropentane is catalyzed by Et3Si[B(C6F5)4] and uses
      Et3SiH as the source of H. Ar-CF3 compounds are converted to Ar-CH3 and
      fluropentane to pentane. The reaction is thought to proceed via abstraction of F-
      by Et3Si[B(C6F5)4], and the substituent effects are consistent with this
      hypothesis.

PMID- 15740112
TI  - Ti-crossed-Claisen condensation between carboxylic esters and acid chlorides or
      acids: a highly selective and general method for the preparation of various beta
      keto esters.
AB  - Ti-crossed-Claisen condensation between a 1:1 mixture of carboxylic esters and
      acid chlorides promoted by TiCl4-Bu3N-N-methylimidazole proceeded successfully to
      give various beta-keto esters in good yields with excellent selectivities (19
      examples, approximately 48-95% yield; cross/self-selectivity = approximately 96/4
      99/1). The present method was extended to the condensation between a 1:1 mixture
      of carboxylic acids and carboxylic esters (six examples, approximately 70-92%
      yield; cross/self-selectivity = approximately 91/9-99/1). To demonstrate the
      utility of the present two Ti-crossed-Claisen condensations, we performed a
      couple of efficient short-step syntheses of two natural, representative, and
      useful perfumes, cis-jasmone and (R)-muscone.

PMID- 15740113
TI  - Syntheses of metallabenzynes from an allenylcarbene complex.
AB  - Treatment of the allenylcarbene complex OsCl2(=CPh-CH=C=CHPh)(PPh3)2 with
      (PPh3)AuCCR in the presence of HNEt3Cl in CH2Cl2 produces osmabenzynes
      Os(CC(R)=C(CH2Ph)CH=CPh)Cl2(PPh3)2.

PMID- 15740114
TI  - Enantioselective friedel-crafts alkylations with benzoylhydrazones promoted by a
      simple strained silacycle reagent.
AB  - The enantioselective Friedel-Crafts reaction of electron-rich arenes and
      heteroarenes with the benzoylhydrazone of isopropyl glyoxylate mediated by a
      simple chiral silane Lewis acid is described. The reactions are highly practical,
      as demonstrated by a larger scale (5 g of the hydrazone) reaction in which the
      recovery of the pseudoephedrine in 99% yield was achieved. A simple model is
      advanced to explain the observed enantioselectivity.

PMID- 15740115
TI  - Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both
      sulfur atoms in lipoic acid are contributed by the same lipoyl synthase
      polypeptide.
AB  - Lipoyl synthase catalyzes the final step in the de novo biosynthesis of the
      lipoyl cofactor, which is the insertion of two sulfur atoms into an octanoyl
      chain that is bound in an amide linkage to a conserved lysine on a lipoyl
      accepting protein. We show herein that the sulfur atoms in the lipoyl cofactor
      are derived from lipoyl synthase itself, and that each lipoyl synthase
      polypeptide contributes both of the sulfur atoms to the intact cofactor.

PMID- 15740116
TI  - Single-crystalline LaB6 nanowires.
AB  - Lanthanum hexaboride nanowires produced by chemical vapor deposition are single
      crystalline and grown along the [111] direction. Streaks appearing in the
      electron diffraction spots indicate the lateral direction perpendicular to the
      nanowire growth axis.

PMID- 15740117
TI  - Observation of excited-state proton transfer in green fluorescent protein using
      ultrafast vibrational spectroscopy.
AB  - The photodynamics of wtGFP have been studied by ultrafast time-resolved infrared
      spectroscopy (TIR). In addition to the expected bleaching and transient infrared
      absorption of bands associated with the chromophore, we observe the dynamics of
      the proton relay reaction in the protein. Protonation of a protein carboxylate
      group occurs on the tens of picoseconds time scale following photoexcitation.
      Comparison with data for mutant GFPs, in which excited-state proton transfer has
      been disabled, supports the assignment of the carboxylate to the side chain of
      E222, a component of the hydrogen bonding network that links the two ends of the
      chromophore. The TIR data show that the rate-limiting step in the proton relay is
      deprotonation of the chromophore.

PMID- 15740119
TI  - Aerobic oxidative amination of unactivated alkenes catalyzed by palladium.
AB  - The first examples of palladium-catalyzed oxidative amination of unactivated
      alkyl olefins have been identified. To be successful, these reactions must be
      conducted under cocatalyst-free conditions that involve direct dioxygen-coupled
      turnover of the palladium catalyst. The oxidative amination products of
      norbornene and other cyclic alkenes implicate a cis-aminopalladation mechanism.

PMID- 15740118
TI  - Catalytic asymmetric synthesis of chiral allylic esters.
AB  - Trichloroacetimidate derivatives of prochiral (Z)-2-alken-1-ols react at room
      temperature with carboxylic acids to give chiral 3-acyloxy-1-alkenes in high
      enantiopurity in the presence of di-mu-acetatobis[(eta5-(S)-(pR)-2-(2'-(4'
      methylethyl)oxazolinyl)cyclopentadienyl,1-C,3'-N)(eta4
      tetraphenylcyclobutadiene)cobalt]dipalladium (COP-OAc) or its enantiomer. This
      reaction has broad scope, proceeds with predictable high stereoinduction, is
      accomplished at room temperature using high substrate concentrations and low
      catalyst loadings, and likely proceeds by a novel mechanism.

PMID- 15740120
TI  - Biomimetic synthesis and structure elucidation of rubicordifolin, a cytotoxic
      natural product from Rubia cordifolia.
AB  - The biomimetic synthesis and full structural elucidation of rubicordifolin, a
      cytotoxic natural product isolated from Rubia cordifolia, is described.

PMID- 15740121
TI  - Rhodium-catalyzed isomerization of alpha-arylpropargyl alcohols to indanones:
      involvement of an unexpected reaction cascade.
AB  - A rhodium-catalyzed isomerization of alpha-arylpropargyl alcohols to indanones
      has been developed under mild conditions. Considering the ease of preparation of
      these propargyl alcohols (terminal alkynes + aromatic aldehydes), this method
      provides a new way of constructing indanones with high efficiency. By the
      mechanistic investigations using deuterium-labeled substrates, it has also been
      demonstrated that the reaction goes through an unexpected cascade, with a 1,4
      hydrogen shift being the turnover-limiting step of the catalytic cycle.

PMID- 15740122
TI  - Benzene-free synthesis of catechol: interfacing microbial and chemical catalysis.
AB  - The toxicity of aromatics frequently limits the yields of their microbial
      synthesis. For example, the 5% yield of catechol synthesized from glucose by
      Escherichia coli WN1/pWL1.290A under fermentor-controlled conditions reflects
      catechol's microbial toxicity. Use of in situ resin-based extraction to reduce
      catechol's concentration in culture medium and thereby its microbial toxicity
      during its synthesis from glucose by E. coli WN1/pWL1.290A led to a 7% yield of
      catechol. Interfacing microbial with chemical synthesis was then explored where
      glucose was microbially converted into a nontoxic intermediate followed by
      chemical conversion of this intermediate into catechol. Intermediates examined
      include 3-dehydroquinate, 3-dehydroshikimate, and protocatechuate. 3
      Dehydroquinate and 3-dehydroshikimate synthesized, respectively, by E. coli
      QP1.1/pJY1.216A and E. coli KL3/pJY1.216A from glucose were extracted and then
      reacted in water heated at 290 degrees C to afford catechol in overall yields
      from glucose of 10% and 26%, respectively. The problematic extraction of these
      catechol precursors from culture medium was subsequently circumvented by high
      yielding chemical dehydration of 3-dehydroquinate and 3-dehydroshikimate in
      culture medium followed by extraction of the resulting protocatechuate. After
      reaction of protocatechuate in water heated at 290 degrees C, the overall yields
      of catechol synthesized from glucose via chemical dehydration of 3-dehydroquinate
      and chemical dehydration of 3-dehydroshikimate were, respectively, 25% and 30%.
      Direct synthesis of protocatechuate from glucose using E. coli KL3/pWL2.46B
      followed by its extraction and chemical decarboxylation in water gave a 24%
      overall yield of catechol from glucose. In situ resin-based extraction of
      protocatechaute synthesized by E. coli KL3/pWL2.46B followed by chemical
      decarboxylation of this catechol percursor was then examined. This employment of
      both strategies for dealing with the microbial toxicity of aromatic products led
      to the highest overall yield with catechol synthesized in 43% overall yield from
      glucose.

PMID- 15740123
TI  - Albumin-conjugated corrole metal complexes: extremely simple yet very efficient
      biomimetic oxidation systems.
AB  - An extremely simple biomimetic oxidation system, consisting of mixing metal
      complexes of amphiphilic corroles with serum albumins, utilizes hydrogen peroxide
      for asymmetric sulfoxidation in up to 74% ee. The albumin-conjugated manganese
      corroles also display catalase-like activity, and mechanistic evidence points
      toward oxidant-coordinated manganese(III) as the prime reaction intermediate.

PMID- 15740124
TI  - Isotope effects, dynamics, and the mechanism of solvolysis of aryldiazonium
      cations in water.
AB  - The mechanism of the heterolytic solvolysis of p-tolyldiazonium cation in water
      was studied by a combination of kinetic isotope effects, theoretical
      calculations, and dynamics trajectories. Significant (13)C kinetic isotope
      effects were observed at the ipso (k(12)C/k(13)C = 1.024), ortho (1.017), and
      meta (1.013) carbons, indicative of substantial weakening of the C(2)-C(3) and
      C(5)-C(6) bonds at the transition state. This is qualitatively consistent with a
      transition state forming an aryl cation, but on a quantitative basis, simple
      S(N)1 heterolysis does not account best for the isotope effects. Theoretical
      S(N)2Ar transition structures for concerted displacement of N(2) by a single
      water molecule lead to poor predictions of the experimental isotope effects. The
      best predictions of the (13)C isotope effects arose from transition structures
      for the heterolytic process solvated by clusters of water molecules. These
      structures, formally saddle points for concerted displacements on the potential
      energy surface, may be described as transition structures for solvent
      reorganization around the aryl cation. Quasiclassical dynamics trajectories
      starting from these transition structures afforded products very slowly, compared
      to a similar S(N)2 displacement, and the trajectories often afforded long-lived
      aryl cation intermediates. Critical prior evidence for aryl cation intermediates
      is reconsidered with the aid of DFT calculations. Overall, the nucleophilic
      displacement process for aryldiazonium ions in water is at the boundary between
      S(N)2Ar and S(N)1 mechanisms, and an accurate view of the reaction mechanism
      requires consideration of dynamic effects.

PMID- 15740125
TI  - A deoxyribozyme that forms a three-helix-junction complex with its RNA substrates
      and has general RNA branch-forming activity.
AB  - We recently used in vitro selection to identify 7S11, a deoxyribozyme that
      synthesizes 2',5'-branched RNA. The 7S11 DNA enzyme mediates the nucleophilic
      attack of an adenosine 2'-hydroxyl group at a 5'-triphosphate, forming 2',5'
      branched RNA in a reaction that resembles the first step of in vivo RNA splicing.
      Here, we describe 7S11 characterization experiments that have two important
      implications for nucleic acid chemistry and biochemistry. First, on the basis of
      a comprehensive analysis of its substrate sequence requirements, 7S11 is shown to
      be generally applicable for the synthesis of a wide range of 2',5'-branched RNAs.
      Strict substrate sequence requirements are found at the two RNA nucleotides that
      directly form the branched linkage, and these requirements correspond to those
      nucleotides found most commonly at these two positions in natural spliced RNAs.
      Outside of these two nucleotides, most substrate sequences are tolerated with
      useful ligation activity, although rates and yields vary. Because chemical
      synthesis approaches to branched RNA are extremely limited in scope, the
      deoxyribozyme-based route using 7S11 will enable many experiments that require
      branched RNA. Second, comprehensive nucleotide covariation experiments
      demonstrate that 7S11 and its RNA substrates adopt a three-helix-junction
      structure in which the branch-site nucleotide is located at the intersection of
      the three helices. Because many natural ribozymes have multi-helix junctions,
      7S11 is an interesting model system for catalytic nucleic acids.

PMID- 15740126
TI  - Investigating cellular signaling reactions in single attoliter vesicles.
AB  - Understanding cellular signaling mediated by cell surface receptors is key to
      modern biomedical research and drug development. The discovery of a growing
      number of potential molecular targets and therapeutic compounds requires
      downscaling and accelerated functional screening. Receptor-mediated cellular
      responses are typically investigated on single cells or cell populations. Here,
      we show how to monitor cellular signaling reactions at a yet unreached
      miniaturization level. On the basis of our observations, cytochalasin induces
      mammalian cells to extrude from their plasma membrane submicrometer-sized native
      vesicles. They comprise functional cell surface receptors correctly exposing
      their extracellular ligand binding sites on the outer vesicle surface and
      retaining cytosolic proteins in the vesicle interior. As a prototypical example,
      ligand binding to the ionotropic 5-HT(3) receptor and subsequent transmembrane
      Ca(2+) signaling were monitored in single attoliter vesicles. Thus, native
      vesicles are the smallest autonomous containers capable of performing cellular
      signaling reactions under physiological conditions. Because a single cell
      delivers about 50 native vesicles, which can be isolated and addressed as
      individuals, our concept allows multiple functional analyses of individual cells
      having a limited availability and opens new vistas for miniaturized bioanalytics.

PMID- 15740127
TI  - High molecular weight supramolecular polymers containing both terpyridine metal
      complexes and ureidopyrimidinone quadruple hydrogen-bonding units in the main
      chain.
AB  - Using a hydroxy-functionalized terpyridine as initiator, a poly(epsilon
      caprolactone) containing one terpyridine endgroup was prepared by tin octanoate
      catalyzed controlled ring-opening polymerization. The omega-hydroxy group of this
      polymer was subsequently reacted with an isocyanato-ureidopyrimidinone, resulting
      for the first time in polymers bearing a metal-coordinating ligand on the one and
      a hydrogen-bonding unit on the other chain end. Hydrogen-bonded supramolecular
      dimers were shown to be present in chloroform solution. The subsequent addition
      of iron(II) ions resulted in the formation of high molecular weight
      supramolecular polymers with novel properties resulting from the combination of
      both types of noncovalent interactions in the main chain, as could be shown using
      capillary viscosimetry and rheometry.

PMID- 15740128
TI  - Molecular recognition of trigonal oxyanions using a ditopic salt receptor:
      evidence for anisotropic shielding surface around nitrate anion.
AB  - A ditopic, macrobicyclic receptor with adjacent anion and cation binding sites is
      able to extract a range of monovalent salts into chloroform solution. The
      structures of the receptor complexed with KAcO, LiNO(3), NaNO(3), KNO(3), and
      NaNO(2) are characterized in solution by NMR spectroscopy and in the solid state
      by X-ray crystallography. The sodium and potassium salts are bound to the
      receptor as contact ion-pairs, with the metal cation located in the receptor's
      crown ether ring and the trigonal oxyanion hydrogen bonded to the receptor NH
      residues. The solid-state structure of the LiNO(3) complex has a bridging water
      molecule between the cation and anion. In all solid-state structures, the
      trigonal oxyanion is not located symmetrically inside the receptor cavity. It
      appears that anion orientation is controlled by a complex interplay of steric
      factors, coordination bonding to the metal cation, and hydrogen bonding with the
      receptor NH residues. An important feature with this latter effect is the fact
      that hydrogen bonds directed toward the oxygen lone pairs on a trigonal oxyanion
      are stronger than hydrogen bonds to the pi-electrons. In solution, the (1)H NMR
      spectra of the nitrate and nitrite salt complexes are noteworthy because several
      receptor signals, including the NH protons, undergo unusual upfield movements in
      chemical shift upon complexation. This is a reflection of the diamagnetic
      anisotropy of these trigonal oxyanions. The magnetic shielding surface for the
      NO(3)(-) anion is calculated using density functional theory and shown to have a
      shielding region directly above the central nitrogen.

PMID- 15740129
TI  - A photoinducible beta-hairpin.
AB  - A photochromic azobenzene linker was incorporated as a turn element into an amino
      acid sequence known to fold into a beta-hairpin structure in aqueous solution.
      Oligomer formation when the linker was in its thermodynamically favored trans
      form prohibited structure determination. Light-induced conformational change of
      the linker to the cis form led to the formation of monomers which exhibited a
      well-defined beta-hairpin structure as determined by (1)H NMR. The rate of the
      light-induced cis-to-trans isomerization of the azobenzene-containing peptide was
      30% slower compared to the unsubstituted chromophore. These results suggest that
      suitably substituted azobenzenes can be used as photoinducible turn elements to
      investigate and control the folding and stability of beta-sheets.

PMID- 15740130
TI  - Reinforced HNA backbone hydration in the crystal structure of a decameric HNA/RNA
      hybrid.
AB  - The crystal structure of a decameric HNA/RNA (HNA = 2',3'-dideoxy-1',5'-anhydro-d
      arabinohexitol nucleic acid) hybrid with the RNA sequence 5'-GGCAUUACGG-3' is the
      first crystal structure of a hybrid duplex between a naturally occurring nucleic
      acid and a strand, which is fully modified to contain a six-membered ring instead
      of ribose. The presence of four duplex helices in the asymmetric unit allows for
      a detailed discussion of hydration, which revealed a tighter spinelike backbone
      hydration for the HNA- than for the RNA-strands. The reinforced backbone
      hydration is suggested to contribute significantly to the exceptional stability
      of HNA-containing duplexes and might be one of the causes for the evolutionary
      preference for ribose-derived nucleic acids.

PMID- 15740131
TI  - Design and synthesis of an expanded porphyrin that has selectivity for the c-MYC
      G-quadruplex structure.
AB  - Cationic porphyrins are known to bind to and stabilize different types of G
      quadruplexes. Recent studies have shown the biological relevance of the
      intramolecular parallel G-quadruplex as a transcriptional silencer in the c-MYC
      promoter. TMPyP4 also binds to this G-quadruplex and most likely converts it to a
      mixed parallel/antiparallel G-quadruplex with two external lateral loops and one
      internal propeller loop, suppressing c-MYC transcriptional activation. To achieve
      therapeutic selectivity by targeting G-quadruplexes, it is necessary to
      synthesize drugs that can differentiate among the different types of G
      quadruplexes. We have designed and synthesized a core-modified expanded porphyrin
      analogue, 5,10,15,20-[tetra(N-methyl-3-pyridyl)]-26,28-diselenasapphyrin chloride
      (Se2SAP). Se2SAP converts the parallel c-MYC G-quadruplex into a mixed
      parallel/antiparallel G-quadruplex with one external lateral loop and two
      internal propeller loops, resulting in strong and selective binding to this G
      quadruplex. A Taq polymerase stop assay was used to evaluate the binding of
      TMPyP4 and Se2SAP to G-quadruplex DNA. Compared to TMPyP4, Se2SAP shows a greater
      selectivity for and a 40-fold increase in stabilization of the single lateral
      loop hybrid. Surface plasmon resonance and competition experiments with duplex
      DNA and other G-quadruplexes further confirmed the selectivity of Se2SAP for the
      c-MYC G-quadruplex. Significantly, Se2SAP was found to be less photoactive and
      noncytotoxic in comparison to TMPyP4. From this study, we have identified an
      expanded porphyrin that selectively binds with the c-MYC G-quadruplex in the
      presence of duplex DNA and other G-quadruplexes.

PMID- 15740132
TI  - Enantioselective esterification of prochiral phosphonate pendants of a
      polyphenylacetylene assisted by macromolecular helicity: storage of a dynamic
      macromolecular helicity memory.
AB  - A poly(phenylacetylene) bearing a phosphonic acid monoethyl ester as the pendant
      forms a one-handed helical structure induced by an optically active amine, and
      this helicity can be "memorized"after the amine is replaced by achiral diamines.
      The helicity memory lasts for an extremely long time but spontaneously disappears
      after the achiral diamines are removed by a stronger acid, indicating the dynamic
      nature of the helicity memory. Here we report that such a dynamic memory could be
      "stored" after the pendant was converted to its methyl ester with diazomethane,
      resulting in the generation of a phosphorus stereogenic center with optical
      activity. The esterification enantioselectively proceeded through chirality
      transfer from the induced helical conformation or the helicity memory of the
      polyacetylene backbone. Although the enantioselectivity was low, the pendant
      chirality was significantly amplified in the polymer backbone at low
      temperatures, resulting in higher optical activity as an excess single-handed
      helix than that expected from the enantiomeric excess of the pendants.

PMID- 15740134
TI  - Single turn peptide alpha helices with exceptional stability in water.
AB  - Cyclic pentapeptides are not known to exist in alpha-helical conformations. CD
      and NMR spectra show that specific 20-membered cyclic pentapeptides, Ac-(cyclo
      1,5) [KxxxD]-NH(2) and Ac-(cyclo-2,6)-R[KxxxD]-NH(2), are highly alpha-helical
      structures in water and independent of concentration, TFE, denaturants, and
      proteases. These are the smallest alpha-helical peptides in water.

PMID- 15740133
TI  - Design and synthesis of N-maleimido-functionalized hydrophilic polymers via
      copper-mediated living radical polymerization: a suitable alternative to
      PEGylation chemistry.
AB  - A series of alpha-functional maleimide polymethacrylates (M(n) = 4.1-35.4 kDa,
      PDi = 1.06-1.27) have been prepared via copper-catalyzed living radical
      polymerization (LRP). Two independent synthetic protocols have been successfully
      developed and the polymers obtained in multigram scale, with an 80-100% content
      of maleimide reactive chain ends, depending on the method employed. A method for
      the synthesis of amino-terminated polymers, starting from Boc-protected amino
      initiators, has also been developed, as these derivatives are key intermediates
      in one of the two processes studied in the present work. The alternative
      synthetic pathway involves an initiator containing a maleimide unit "protected"
      as a Diels-Alder adduct. After the polymerization step, the maleimide
      functionality has been reintroduced by retro-Diels-Alder reaction, by simply
      refluxing those polymers in toluene for 7 h. These maleimido-terminated
      materials, poly(methoxyPEG((475))) methacrylates and poly(glycerol)
      methacrylates, differ for both the nature and size of the polymer side branches
      and showed an excellent solubility in water, a property that made them an ideal
      candidate for the synthesis of new polymer-(poly)peptide biomaterials. These
      functional polymers have been successfully employed in conjugation reactions in
      the presence of thiol-containing model substrates, namely, reduced glutathione
      (gamma-Glu-Cys-Gly) and the carrier protein, bovine serum albumin (BSA), in 100
      mM phosphate buffer (pH 6.8-7.4) and ambient temperature.

PMID- 15740135
TI  - Chiral supramolecular polymers formed by host-guest interactions.
AB  - alpha-Cyclodextrin with a p-t-butoxyaminocinnamoylamino group in the 3-position
      (3-p-(t)()BocCiNH-alpha-CD) has been found to form a supramolecular polymer in an
      aqueous solution. The degree of polymerization of the supramolecular polymer is
      higher than 15 at 20 mM, as proved by VPO (vapor pressure osmometry) measurements
      and turbo ion spray TOF MS measurements. The existence of
      substitution/substitution interactions between adjacent monomers of the
      supramolecular polymer have been confirmed by the observation of positive and
      negative Cotton bands in circular dichroism spectra. The mechanism for the
      induction of the chirality was confirmed using model compounds. The substituents
      were found to exist as a left-handed anti configuration in supramolecular
      polymers. The supramolecular polymer was found to take a helical structure. The
      structure of the supramolecular polymer was observed by STM measurements.

PMID- 15740136
TI  - Molecular containers based on amphiphilic PS-b-PMVE dendrigraft copolymers:
      topology, organization, and aqueous solution properties.
AB  - The synthesis, characteristics, and properties of amphipatic, water-soluble
      dendrigrafts, with a polystyrene core and polystyrene-b-poly(methyl vinyl ether)
      (PS-b-PMVE) diblock as external branches, are described. The dendrigrafts are
      observed by AFM and TEM as egglike or long cylindrical objects which can self
      organize intramolecularly in segregated subdomains forming flowerlike or strings
      of flowerlike objects. In organic solvents the dendrigrafts behave as fully
      soluble isolated macromolecules and show in water a low critical solubility
      temperature (LCST) at t > 30 degrees C. The ability of the amphiphilic PS-b-PMVE
      dendrigrafts to complex and transport in water organic (pyrene) and metallo
      organic (manganese tetraphenyl porphyrin) molecules is investigated. The
      possibility to stabilize the high oxidation state of metallo-porphyrin complexes
      through their encapsulation into the dendrigraft is shown.

PMID- 15740137
TI  - Molecular recognition in a thermoplastic elastomer.
AB  - Selective incorporation of bisurea guests in thermoplastic elastomers with
      poly(tetrahydrofuran) soft blocks and bisurea containing hard blocks is observed
      when the distances between the urea groups of host and guest match. The
      incorporation leads to significant modulation of mechanical properties. With
      bisurea-functionalized dyes as guests, a strong difference in extractability by
      detergent solution was shown between dyes differing by just one methylene unit
      between urea groups. Upon elongation of elastomer films, strong differences in
      alignability of matching and nonmatching dyes were observed.

PMID- 15740138
TI  - Hydroxyl stereochemistry and amine number within poly(glycoamidoamine)s affect
      intracellular DNA delivery.
AB  - Nucleic acid drugs have great potential to treat many devastating aliments, but
      their application has been hindered by the lack of efficacious and nontoxic
      delivery vehicles. Here, a new library of poly(glycoamidoamine)s (D1-D4, G1-G4,
      and M1-M4) has been synthesized by polycondensation of esterified d-glucaric acid
      (D), dimethyl-meso-galactarate (G), and d-mannaro-1,4:6,3-dilactone (M) with
      diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and
      pentaethylenehexamine (4). The stereochemistry of the carbohydrate hydroxyl
      groups and the number of amine units have been systematically changed in an
      effort to examine how the polymer chemistry affects the plasmid DNA (pDNA)
      binding affinity, the compaction of pDNA into nanoparticles (polyplexes), the
      material cytotoxicity, and the efficacy of nucleic acid delivery. The polymers
      with four secondary amines (D4, G4, and M4) between the carbohydrates were found
      to have the highest pDNA binding affinity and the galactarate polymers generally
      yielded the smallest polyplexes. Delivery studies with pDNA containing the
      firefly luciferase or beta-galactosidase reporter genes in BHK-21, HeLa, and
      HepG2 cells demonstrated that all of the poly(glycoamidoamine)s deliver pDNA
      without cytotoxicity. Polymers D4, G4, and M4 displayed the highest delivery
      efficiency, where G4 was found to be a particularly effective delivery vehicle.
      Heparin competition assays indicated that this may be a result of the higher pDNA
      binding affinity displayed by G4 as compared to D4 and M4. Polyplexes formed by
      polymers with weaker pDNA affinities may dissociate at the cell surface due to
      interactions with negatively charged glycosaminoglycans, which would cause a
      decrease in the number of polyplexes that are endocytosed.

PMID- 15740139
TI  - beta-Sheet ligands in action: KLVFF recognition by aminopyrazole hybrid receptors
      in water.
AB  - Little is known about the precise mechanism of action of beta-sheet ligands,
      hampered by the notorious solubility problems involved with protein misfolding
      and amyloid formation. Recently the nucleation site for the pathogenic
      aggregation of the Alzheimer's peptide was identified as the KLVFF sequence in
      the central region of Abeta. A combination of two aminopyrazole ligands with di-
      or tripeptides taken from this key fragment now furnished water-soluble Abeta
      specific ligands which allow model investigations in water. A detailed
      conformational analysis provides experimental evidence for an increased beta
      sheet content induced in the peptide. Strong indications were also found for the
      peptide backbone recognition via hydrogen bonds plus hydrophobic contributions
      between aminopyrazole nuclei and Phe residues. The affinity of these new ligands
      toward the KKLVFF fragment is highly dependent on their sequence and composition
      from natural and artificial amino acids. Thus, for the first time, detailed
      insight is gained into the complexation of beta-sheet ligands with model peptides
      taken directly from Abeta.

PMID- 15740140
TI  - Photoswitching of single association force between a pair of photoionizable
      spirobenzopyrans.
AB  - We have measured the single intermolecular force of a typical photoionizable
      molecule, spirobenzopyran, by means of atomic force microscopy, which has proven
      to be useful in measuring directly single molecular forces. The spirobenzopyran
      moiety was immobilized covalently on both Au-coated probe tips and substrates by
      use of a self-assembled monolayer of a hexanethiol derivative incorporating a
      terminal spirobenzopyran moiety, 1'-(6'-mercaptohexyl)-3',3'-dimethylindolino-6
      nitrospiro-(2H-1-benzopyran-2,2'-indoline). Force curve measurements were carried
      out using the spirobenzopyran-modified probe tip and substrate under dark
      conditions and in situ UV light irradiation. The adhesion force observed in a
      polar solvent (i.e., ethanol) was increased substantially under in situ UV light
      irradiation, which caused photoisomerization of the spirobenzopyran moiety bound
      to both tip and substrate from its electrically neutral spiropyran form to the
      corresponding zwitterionic merocyanine one. Statistical analyses of the observed
      force by autocorrelation technique have revealed that the photoionization
      enhanced by UV light caused a remarkable increase in the single intermolecular
      force of the photochromic compound.

PMID- 15740141
TI  - Bimetallic anilido-aldimine zinc complexes for epoxide/CO2 copolymerization.
AB  - Acyclic o-phenylene-bridged bis(anilido-aldimine) compounds, o
      C(6)H(4){C(6)H(2)R(2)N=CH-C(6)H(4)-(H)N(C(6)H(3)R'(2))}(2) and related 30
      membered macrocyclic compounds, o-C(6)H(4){C(6)H(2)R'(2)N=CH-C(6)H(4)-(H)N
      C(6)H(2)R(2)}(2) (o-C(6)H(4)) are prepared. Successive additions of Me(2)Zn and
      SO(2) gas to the bis(anilido-aldimine) compounds afford quantitatively dinuclear
      mu-methylsulfinato zinc complexes, o-C(6)H(4){(C(6)H(2)R(2)N=CH-C(6)H(4)
      N(C(6)H(3)R'(2))-kappa(2)-N,N)Zn(mu-OS(O)Me)}(2) (R = iPr and R' = iPr, 29; R =
      Et and R' = Et, 30; R = Me and R'= Me, 31; R = Me and R' = iPr, 32; R = Et and R'
      = Me, 33; R = Et and R' = iPr, 34; R = iPr and R' = Et, 35) and o
      C(6)H(4){C(6)H(2)R'(2)N=CH-C(6)H(4)-N-C(6)H(2)R(2)-kappa(2)-N,N)Zn(mu
      OS(O)Me)}(2) (o-C(6)H(4)) (R = Et and R'= Et, 36; R = Me and R' = Me, 37; R = iPr
      and R' = Me, 38; R = Et and R' = Me, 39; R = Me and R'= iPr, 40). Molecular
      structures of 34 and 40 are confirmed by X-ray crystallography. Complexes 30-35
      show high activity for cyclohexene oxide/CO(2) copolymerization at low
      [Zn]/[monomer] ratio (1:5600), whereas the complex of mononucleating beta
      diketiminate {[(C(6)H(3)Et(2))N=C(Me)CH=C(Me)N(C(6)H(3)Et(2))]Zn(mu-OS(O)Et)}(2)
      shows negligible activity in the same condition. Activity is sensitive to the N
      aryl ortho substituents and the highest activity is observed with 32. Turnover
      number up to 2980 and molecular weight (M(n)) up to 284 000 are attained with 32
      at such a highly diluted condition as [Zn]/[monomer] = 1:17 400. Macrocyclic
      complexes 36-40 show negligible activity for copolymerization.

PMID- 15740142
TI  - High-pressure dissociation of crystalline para-diiodobenzene: optical experiments
      and Car-Parrinello calculations.
AB  - We have investigated the high-pressure properties of the molecular crystal para
      diiodobenzene, by combining optical absorption, reflectance, and Raman
      experiments with Car-Parrinello simulations. The optical absorption edge exhibits
      a large red shift from 4 eV at ambient conditions to about 2 eV near 30 GPa.
      Reflectance measurements up to 80 GPa indicate a redistribution of oscillator
      strength toward the near-infrared. The calculations, which describe correctly the
      two known molecular crystal phases at ambient pressure, predict a nonmolecular
      metallic phase, stable at high pressure. This high-density phase is characterized
      by an extended three-dimensional network, in which chemically bound iodine atoms
      form layers connected by hydrocarbon bridges. Experimentally, Raman spectra of
      samples recovered after compression show vibrational modes of elemental solid
      iodine. This result points to a pressure-induced molecular dissociation process
      which leads to the formation of domains of iodine and disordered carbon.

PMID- 15740143
TI  - Transmutation of fullerenes.
AB  - Fullerenes were pyrolyzed by subliming them into a stream of flowing argon gas
      and then passing them through an oven heated to approximately 1000 degrees C.
      C(76), C(78), and C(84) all readily lost carbons to form smaller fullerenes. In
      the case of C(78), some isomerization was seen. Pyrolysis of (3)He@C(76) showed
      that all or most of the (3)He was lost during the decomposition. C(60) passes
      through the apparatus with no decomposition and no loss of helium.

PMID- 15740144
TI  - Surface-catalyzed growth of polymethylene-rich copolymer films on gold.
AB  - We report the preparation of a new class of copolymer films that consist of
      polymethylene (PM) with a low percentage ( approximately 1-4%) of randomly
      distributed ethyl ester side groups, consistent with poly(methylene-co-ethyl
      acetate). The films are prepared through a surface-catalyzed polymerization on
      gold surfaces upon exposure to a dilute solution of diazomethane (DM) and ethyl
      diazoacetate (EDA) in ether at 0 degrees C. While EDA alone does not polymerize
      at gold surfaces but DM does decompose on gold to grow PM films, the combined
      presence of EDA and DM results in dramatic enhancements in film growth and
      promotes an alternative mechanism for propagation as compared with that for the
      PM homopolymerization. The rate of copolymer film growth is constant over a
      approximately 24 h period, consistent with a controlled polymerization in which
      chain terminations are minimized. Carefully controlled experiments indicate that
      chain propagation does not occur at the outer film-solvent interface, but more
      likely, at the film-metal interface, suggesting a catalyzed insertion mechanism
      that extends the chain and pushes the outer chain termini further away from the
      metal-polymer interface. The results also suggest that adsorbed intermediates of
      EDA function as co-catalysts to promote the propagation reaction. Of particular
      importance for materials modification is that the ester side chains of these
      copolymer films can be hydrolyzed to carboxylate groups that exhibit pH-dependent
      wettability.

PMID- 15740145
TI  - Solid-state NMR study of MCM-41-type mesoporous silica nanoparticles.
AB  - A systematic study of the surface of MCM-41-type mesoporous silica nanoparticles
      prepared under low surfactant concentration was carried out using high-resolution
      solid-state nuclear magnetic resonance spectroscopy. The structures and
      concentrations of various species present during dehydration and rehydration of
      mesoporous silicas between -25 and 500 degrees C were detailed by employing one
      dimensional and two-dimensional (1)H, (13)C, and (29)Si NMR, including (1)H
      signal intensity measurements, (1)H-(1)H homonuclear correlation experiments
      (double quantum, exchange, and RFDR), and (1)H-(29)Si heteronuclear correlation
      NMR. These experiments employed high MAS rates of up to 45 kHz. The study shows
      that the surfactant (CTAB) was almost completely removed by acid extraction. The
      residual molecules assumed prone positions along the pores, with the tailgroup
      being most mobile. The weakly adsorbed water was hydrogen bonded to the silanol
      groups, all of which were involved in such bonds under ambient humidity. Specific
      structures involving water and silanol groups were proposed for various stages of
      thermal treatment, which included dehydration, dehydroxylation, and subsequent
      rehydration.

PMID- 15740146
TI  - Pentacene disproportionation during sublimation for field-effect transistors.
AB  - At moderate temperatures in flowing gas, pentacene undergoes a disproportionation
      reaction to produce 6,13-dihydropentacene (DHP) and a series of polycondensed
      aromatic hydrocarbons, including the previously unknown peripentacene (PP). The
      process requires activation by heating to 320 degrees C and is possibly catalyzed
      by impurities such as DHP, 6,13-pentacenequinone (PQ), Al, or Fe found in the
      starting materials. These impurities also result in a decrease in the intrinsic
      field-effect mobility (FEM) of pentacene crystals. Subsequent purifications
      remove such impurities, thus inhibiting the formation of the disproportionation
      products and increasing the FEM of pentacene (2.2 cm(2)/Vs). These results
      clarify the importance of purification of semiconductive materials for
      measurements of intrinsic mobility and optimal device performance.

PMID- 15740147
TI  - Formation and characterization of the hexanuclear platinum cluster [Pt6(mu
      PBu(t)2)4(CO)6](CF3SO3)2 through structural, electrochemical, and computational
      analyses.
AB  - The reaction between equimolar amounts of Pt(3)(mu-PBu(t)()(2))(3)(H)(CO)(2),
      Pt(3)()H, and CF(3)SO(3)H under CO atmosphere affords the triangular species
      [Pt(3)(mu-PBu(t)()(2))(3)(CO)(3)]X, [Pt(3)()(CO)(3)()(+)()]X (X = CF(3)SO(3)(-)),
      characterized by X-ray crystallography, or in an excess of acid, [Pt(6)(mu
      PBu(t)()(2))(4)(CO)(6)]X(2), [Pt(6)()(2+)()]X(2)(). Structural determination
      shows the latter to be a rare hexanuclear cluster with a Pt(4) tetrahedral core
      formed by joining the unbridged sides of two orthogonal Pt(3) triangles. The
      dication Pt(6)()(2+)() features also extensive redox properties as it undergoes
      two reversible one-electron reductions to the congeners [Pt(6)(mu
      PBu(t)()(2))(4)(CO)(6)](+) (Pt(6)()(+)(), E(1/2) = -0.27 V) and Pt(6)(mu
      PBu(t)()(2))(4)(CO)(6) (Pt(6)(), E(1/2) = -0.54 V) and a further quasi-reversible
      two-electron reduction to the unstable dianion Pt(6)()(2)()(-)() (E(1/2) = -1.72
      V). The stable radical (Pt(6)()(+)()) and diamagnetic (Pt(6)()) species are also
      formed via chemical methods by using 1 or 2 equiv of Cp(2)Co, respectively;
      further reduction of Pt(6)()(2+)() causes fast decomposition. The chloride
      derivatives [Pt(6)(mu-PBu(t)()(2))(4)(CO)(5)Cl]X, (Pt(6)()Cl(+)())X, and Pt(6)(mu
      PBu(t)()(2))(4)(CO)(4)Cl(2), Pt(6)()Cl(2)(), observed as side-products in some
      electrochemical experiments, were prepared independently. The reaction leading to
      Pt(3)()(CO)(3)()(+)() has been analyzed with DFT methods, and identification of
      key intermediates allows outlining the reaction mechanism. Moreover, calculations
      for the whole series Pt(6)()(2+)() --> Pt(6)()(2)()(-)()( )()afford the otherwise
      unknown structures of the reduced derivatives. While the primary geometry is
      maintained by increasing electron population, the system undergoes progressive
      and concerted out-of-plane rotation of the four phosphido bridges (from D(2)(d)()
      to D(2) symmetry). The bonding at the central Pt(4) tetrahedron of the
      hexanuclear clusters (an example of 4c-2e(-) inorganic tetrahedral aromaticity in
      Pt(6)()(2+)()) is explained in simple MO terms.

PMID- 15740148
TI  - Single-chain magnet (NEt4)[Mn2(5-MeOsalen)2Fe(CN)6] Made of Mn(III)-Fe(III)
      Mn(III) trinuclear single-molecule magnet with an S(T) = 9/2 spin ground state.
AB  - The cyano-bridged trinuclear compound,
      (NEt(4))[Mn(2)(salmen)(2)(MeOH)(2)Fe(CN)(6)] (1) (salmen(2)(-) = rac-N,N'-(1
      methylethylene)bis(salicylideneiminate)), reported previously by Miyasaka et al.
      (ref 19d) has been reinvestigated using combined ac and dc susceptibility
      measurements. The strong frequency dependence of the ac susceptibility and the
      slow relaxation of the magnetization show that 1 behaves as a single-molecule
      magnet with an S(T) = (9)/(2) spin ground state. Its relaxation time (tau)
      follows an Arrhenius law with tau(0) = 2.5 x 10(-)(7) s and Delta(eff)/k(B) = 14
      K. Moreover, below 0.3 K, tau saturates around 470 s, indicating that quantum
      tunneling of the magnetization becomes the dominant process of relaxation.
      (NEt(4))[Mn(2) (5-MeOsalen)(2)Fe(CN)(6)] (2) (5-MeOsalen(2)(-) = N,N'
      ethylenebis(5-methoxysalicylideneiminate)) is a heterometallic one-dimensional
      assembly made of the trinuclear [Mn(III)(SB)-NC-Fe(III)-CN-Mn(III)(SB)] (SB is a
      salen-type Schiff-base ligand) motif similar to 1. Compound 2 has two types of
      bridges, a cyano bridge (-NC-) and a biphenolate bridge (-(O)(2)-), connecting
      Mn(III) and Fe(III) ions and the two Mn(III) ions, respectively. Both bridges
      mediate ferromagnetic interactions, as shown by modeling the magnetic
      susceptibility above 10 K with g(av) = 2.03, J(Mn)(-)(Fe)/k(B) = +6.5 K, and
      J'/k(B) = +0.07 K, where J' is the exchange coupling between the trimer units.
      The dc magnetic measurements of a single crystal using micro-SQUID and Hall-probe
      magnetometers revealed a uniaxial anisotropy (D(T)/k(B) = -0.94 K) with an easy
      axis lying along the chain direction. Frequency dependence of the ac
      susceptibility and time dependence of the dc magnetization have been performed to
      study the slow relaxation of the magnetization. A mean relaxation time has been
      found, and its temperature dependence has been studied. Above 1.4 K, both
      magnetic susceptibility and relaxation time are in agreement with the dynamics
      described in the 1960s by R. J. Glauber for one-dimensional systems with
      ferromagnetically coupled Ising spins (tau(0) = 3.7 x 10(-)(10) s and
      Delta(1)/k(B) = 31 K). As expected, at lower temperatures below 1.4 K, the
      relaxation process is dominated by the finite-size chain effects (tau'(0) = 3 x
      10(-)(8) s and Delta(2)/k(B) = 25 K). The detailed analysis of this single-chain
      magnet behavior and its two regimes is consistent with magnetic parameters
      independently estimated (J'and D(T)) and allows the determination of the average
      chain length of 60 nm (or 44 trimer units). This work illustrates nicely a new
      strategy to design single-chain magnets by coupling ferromagnetically single
      molecule magnets in one dimension.

PMID- 15740149
TI  - Hydrogen elimination from a hydroxycyclopentadienyl ruthenium(II) hydride: study
      of hydrogen activation in a ligand-metal bifunctional hydrogenation catalyst.
AB  - At high temperatures in toluene, [2,5-Ph(2)-3,4-Tol(2)(eta(5)-C(4)COH)]Ru(CO)(2)H
      (3) undergoes hydrogen elimination in the presence of PPh(3) to produce the
      ruthenium phosphine complex [2,5-Ph(2)-3,4-Tol(2)-(eta(4)
      C(4)CO)]Ru(PPh(3))(CO)(2) (6). In the absence of alcohols, the lack of RuH/OD
      exchange, a rate law first order in Ru and zero order in phosphine, and kinetic
      deuterium isotope effects all point to a mechanism involving irreversible
      formation of a transient dihydrogen ruthenium complex B, loss of H(2) to give
      unsaturated ruthenium complex A, and trapping by PPh(3) to give 6. DFT
      calculations showed that a mechanism involving direct transfer of a hydrogen from
      the CpOH group to form B had too high a barrier to be considered. DFT
      calculations also indicated that an alcohol or the CpOH group of 3 could provide
      a low energy pathway for formation of B. PGSE NMR measurements established that 3
      is a hydrogen-bonded dimer in toluene, and the first-order kinetics indicate that
      two molecules of 3 are also involved in the transition state for hydrogen
      transfer to form B, which is the rate-limiting step. In the presence of ethanol,
      hydrogen loss from 3 is accelerated and RuD/OH exchange occurs 250 times faster
      than in its absence. Calculations indicate that the transition state for
      dihydrogen complex formation involves an ethanol bridge between the acidic CpOH
      and hydridic RuH of 3; the alcohol facilitates proton transfer and accelerates
      the reversible formation of dihydrogen complex B. In the presence of EtOH, the
      rate-limiting step shifts to the loss of hydrogen from B.

PMID- 15740150
TI  - Inducing spin crossover in metallo-supramolecular polyelectrolytes through an
      amphiphilic phase transition.
AB  - A phase transition in an amphiphilic mesophase is explored to deliberately induce
      mechanical strain in an assembly of tightly coupled metal ion coordination
      centers. Melting of the alkyl chains in the amphiphilic mesophase causes
      distortion of the coordination geometry around the central transition metal ion.
      As a result, the crystal field splitting of the d-orbital subsets decreases
      resulting in a spin transition from a low-spin to a high-spin state. The
      diamagnetic-paramagnetic transition is reversible. This concept is demonstrated
      in a metallo-supramolecular coordination polyelectrolyte-amphiphile complex self
      assembled from ditopic bis-terpyridines, Fe(II) as central transition metal, and
      dialkyl phosphates as amphiphiles. The magnetic properties are studied in a
      Langmuir-Blodgett multilayer. The modularity of this concept provides extensive
      control of structure and function from molecular to macroscopic length scales and
      gives access to a wide range of new molecular magnetic architectures such as
      nanostructures, thin films, and liquid crystals.

PMID- 15740152
TI  - Self-assembly of diorganotin(IV) oxides (R = Me, nBu, Ph) and 2,5
      pyridinedicarboxylic acid to polymeric and trinuclear macrocyclic hybrids with
      porous solid-state structures: influence of substituents and solvent on the
      supramolecular structure.
AB  - 2,5-Pyridinedicarboxylic acid has been reacted with three different
      diorganotin(IV) oxides (R = Me, nBu, Ph) to study the molecular and
      supramolecular structures of the resulting diorganotin(IV) 2,5
      pyridinedicarboxylates. It has been found that coordinating solvent molecules can
      change the supramolecular structure completely. The molecular structures found
      are either polymeric (zigzag) or cyclotrimeric; the supramolecular arrangements
      include (i) systems having only loosely bound discrete molecules (van der Waals
      contacts), (ii) systems having a 2D or 3D hydrogen-bonded structure, and (iii)
      systems having a 3D polymeric coordination structure. Channels or cavities are
      formed in several cases. For a particular case, evidence has been provided that
      molecular aggregation to capsules through hydrogen bonding interactions is
      possible in solution.

PMID- 15740151
TI  - Nanometal surface energy transfer in optical rulers, breaking the FRET barrier.
AB  - Optical-based distance measurements are essential for tracking biomolecular
      conformational changes, drug discovery, and cell biology. Traditional Forster
      resonance energy transfer (FRET) is efficient for separation distances up to 100
      A. We report the first successful application of a dipole-surface type energy
      transfer from a molecular dipole to a nanometal surface that more than doubles
      the traditional Forster range (220 A) and follows a 1/R(4) distance dependence.
      We appended a 1.4 nm Au cluster to the 5' end of one DNA strand as the energy
      acceptor and a fluorescein (FAM) to the 5' end of the complementary strand as the
      energy donor. Analysis of the energy transfer on DNA lengths (15, 20, 30, 60bp),
      complemented by protein-induced DNA bending, provides the basis for fully mapping
      the extent of this dipole surface type mechanism over its entire usable range (50
      250 A). Further, protein function is fully compatible with these nanometal-DNA
      constructs. Significantly extending the range of optical based methods in
      molecular rulers is an important leap forward for biophysics.

PMID- 15740153
TI  - Cycloaddition of benzene on Si(100) and its surface conversions.
AB  - A comprehensive ab initio study of the adsorption of benzene on the silicon(100)
      surface is presented. Five potential candidates ([2+2] adduct, [4+2] adduct, two
      tetra-sigma-bonded structures, and one radical-like structure) for the reaction
      product are examined to determine the lowest energy adsorption configuration. A
      [4+2] butterfly structure is determined to be the global minimum (-29.0
      kcal/mol), although one of the two tetra-sigma-bonded structures (-26.7 kcal/mol)
      is similar in energy to it. Multireference perturbation theory suggests that the
      [4+2] addition mechanism of benzene on Si(100) is very similar to the usual Diels
      Alder reaction (i.e., small or zero activation barrier), even though benzene
      adsorption entails the loss of benzene aromaticity during the reaction. On the
      other hand, the [2+2] cycloaddition mechanism is shown to require a relatively
      high activation barrier (17.8 kcal/mol), in which the initial step is to form a
      (relatively strongly bound) van der Waals complex (-8.9 kcal/mol). However, the
      net activation barrier relative to reactants is only 8.9 kcal/mol. Careful
      examination of the interconversion reactions among the reaction products
      indicates that the two tetra-sigma-bonded structures (that are energetically
      comparable to the [4+2] product) can be derived from the [2+2] adduct with
      activation barriers of 15.5 and 21.4 kcal/mol. However, unlike the previous
      theoretical predictions, it is found that the conversion of the [4+2] product to
      the tetra-sigma-bonded structures entails huge barriers (>37.0 kcal/mol) and is
      unlikely to occur. This suggests that the [4+2] product is not only
      thermodynamically the most stable configuration (lowest energy product) but also
      kinetically very stable (large barriers with respect to the isomerization to
      other products).

PMID- 15740154
TI  - Chemical behavior of the biradicaloid (HO...ONO) singlet states of peroxynitrous
      acid. The oxidation of hydrocarbons, sulfides, and selenides.
AB  - Various high levels of theory have been applied to the characterization of two
      higher lying biradicaloid metastable singlet states of peroxynitrous acid. A
      singlet minimum (cis-2) was located that had an elongated O-O distance (2.17 A)
      and was only 12.2 kcal/mol [UB3LYP/6-311+G(3df,2p)+ZPVE] higher in energy than
      its ground-state precursor. A trans-metastable singlet (trans-2) was 10.9
      kcal/mol higher in energy than ground-state HO-ONO. CASSCF(12,10)/6-311+G(d,p)
      calculations predict the optimized geometries of these cis- and trans-metastable
      singlets to be close to those obtained with DFT. Optimization of cis- and trans-2
      within the COSMO solvent model suggests that both exist as energy minima in polar
      media. Both cis- and trans-2 exist as hydrogen bonded complexes with several
      water molecules. These collective data suggest that solvated forms of cis
      2.3H(2)O and trans-2.3H(2)O represent the elusive higher lying biradicaloid
      minima that were recently (J. Am. Chem. Soc. 2003, 125, 16204) advocated as the
      metastable forms of peroxynitrous acid (HOONO). The involvement of metastable
      trans-2 in the gas phase oxidation of methane and isobutane is firmly established
      to take place on the unrestricted [UB3LYP/6-311+G(d,p)] potential energy surface
      (PES) with classical activations barriers for the hydrogen abstraction step that
      are 15.7 and 5.9 kcal/mol lower than the corresponding activation energies for
      producing products methanol and tert-butyl alcohol formed on the restricted PES.
      The oxidation of dimethyl sulfide and dimethyl selenide, two-electron oxidations,
      proceeds by an S(N)2-like attack of the heteroatom lone pair on the O-O bond of
      ground-state peroxynitrous acid. No involvement of metastable forms of HO-ONO was
      discernible.

PMID- 15740155
TI  - Selective calcium ion sensing with a bichromophoric squaraine foldamer.
AB  - Several squaraine tethered bichromophoric podand systems 1a-d and a
      monochromophoric analogue 2 were prepared and characterized. Among these, the
      bichromophore, 1b, containing five oxygen atoms in the flexible podand moiety was
      found to specifically bind Ca(2+) in the presence of other metal ions such as
      K(+), Na(+), and Mg(2+). The selective binding of Ca(2+) is clear from the
      absorption and emission spectral changes as well as by the visual color change of
      1b from light-blue to an intense purple-blue. Benesi-Hildebrand and Job plots
      confirmed a 1:1 binding between 1b and Ca(2+). Signaling of the binding event is
      achieved by the cation-induced folding of the bichromophore and the resultant
      exciton coupling between the squaraine chromophores. The monochromophoric
      squaraine dye 2 failed to give optical signals upon Ca(2+) binding, due to the
      absence of exciton interaction in the bound complex. Titration of the folded
      complex 9 with EDTA released the metal ion from the complex, thereby regaining
      the original absorption and emission properties of the bichromophore. The
      squaraine foldamer 1b reported here is the first example of a selective
      chromogenic Ca(2+) sensor, which works on the principle of exciton interaction in
      the folded Ca(2+) complex of a bichromophore, the optical properties of which are
      similar to those of the "H"-type aggregates of analogous squaraine dyes.

PMID- 15740156
TI  - Nonequilibrium capillary electrophoresis of equilibrium mixtures: a universal
      tool for development of aptamers.
AB  - Aptamers are DNA (or RNA) ligands selected from large libraries of random DNA
      sequences and capable of binding different classes of targets with high affinity
      and selectivity. Both the chances for the aptamer to be selected and the quality
      of the selected aptamer are largely dependent on the method of selection. Here we
      introduce selection of aptamers by nonequilibrium capillary electrophoresis of
      equilibrium mixtures (NECEEM). The new method has a number of advantages over
      conventional approaches. First, NECEEM-based selection has exceptionally high
      efficiency, which allows aptamer development with fewer rounds of selection.
      Second, NECEEM can be equally used for selecting aptamers and finding their
      binding parameters. Finally, due to its comprehensive kinetic capabilities, the
      new method can potentially facilitate selection of aptamers with predefined K(d),
      k(off), and k(on) of the aptamer-target interaction. In this proof-of-principle
      work, we describe the theoretical bases of the method and demonstrate its
      application to a one-step selection of DNA aptamers with nanomolar affinity for
      protein farnesyltransferase.

PMID- 15740157
TI  - High-performance hole-transport layers for polymer light-emitting diodes.
      Implementation of organosiloxane cross-linking chemistry in polymeric
      electroluminescent devices.
AB  - This contribution describes an organosiloxane cross-linking approach to robust,
      efficient, adherent hole-transport layers (HTLs) for polymer light-emitting
      diodes (PLEDs). An example is 4,4'-bis[(p
      trichlorosilylpropylphenyl)phenylamino]biphenyl (TPDSi(2)), which combines the
      hole-transporting efficiency of N,N-diphenyl-N,N-bis(3-methylphenyl)-1,1
      biphenyl)-4,4-diamine) (TPD, prototypical small-molecule HTL material) and the
      strong cross-linking/densification tendencies of organosilanol groups. Covalent
      chemical bonding of TPDSi(2) to PLED anodes (e.g., indium tin oxide, ITO) and its
      self-cross-linking enable fabrication of three generations of insoluble PLED
      HTLs: (1) self-assembled monolayers (SAMs) of TPDSi(2) on ITO; (2) cross-linked
      blend networks consisting of TPDSi(2) + a hole transporting polymer (e.g.,
      poly(9,9-dioctylfluorene-co-N-(4-(3-methylpropyl))diphenylamine), TFB) on ITO;
      (3) TPDSi(2) + TFB blends on ITO substrates precoated with a conventional PLED
      HTL, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS). PLED
      devices fabricated using these new HTLs exhibit comparable or superior
      performance vs comparable devices based on PEDOT-PSS alone. With these new HTLs,
      current efficiencies as high as approximately 17 cd/A and luminances as high as
      approximately 140,000 cd/m(2) have been achieved. Further experiments demonstrate
      that not only do these HTLs enhance PLED anode hole injection but they also
      exhibit significantly greater electron-blocking capacity than PEDOT-PSS. The
      present organosiloxane HTL approach offers many other attractions such as
      convenience of fabrication, flexibility in choosing HTL components, and reduced
      HTL-induced luminescence quenching, and can be applied as a general strategy to
      enhance PLED performance.

PMID- 15740158
TI  - The nature of the supramolecular association of 1,2,5-chalcogenadiazoles.
AB  - Organochalcogen-nitrogen heterocycles such as the 1,2,5-chalcogenadiazoles have a
      distinct tendency to establish intermolecular links in the solid state through
      secondary bonding interactions E...N (E = S, Se, Te). The association of these
      molecules was examined in detail using relativistic density functional theory.
      Although there is an important electrostatic component, the interaction between
      these molecules is dominated by contributions arising from orbital mixing, which
      can be interpreted as the donation of a nitrogen lone pair into the chalcogen
      centered antibonding orbitals. Because of its more polar character and lower
      lying antibonding orbitals, the tellurium derivatives possess the strongest
      association energies; these are so large that the binding strength is comparable
      to that of some hydrogen bonds. In the absence of steric constraints,
      telluradiazoles associate in a coplanar fashion forming ribbon polymers. However,
      bulky susbstituents could be used to direct the formation of either helical
      chains or discrete dimers. In addition to its strength, the coplanar dimer is
      characterized by being rigid, yet no activation barrier is expected for the
      association/dissociation process. These attributes strongly indicate that
      tellurium-nitrogen heterocycles have great potential as building blocks in
      supramolecular architecture.

PMID- 15740159
TI  - Origin of tight binding of a near-perfect transition-state analogue by cytidine
      deaminase: implications for enzyme catalysis.
AB  - Cytidine deaminase (CDA) is a zinc metalloenzyme that catalyzes the hydrolytic
      deamination of cytidine to uridine. Zebularine (ZEB) binds to CDA, and the
      binding process leads to a near-perfect transition-state analogue (TSA) inhibitor
      at the active site with an estimated K(i) value of 1.2 x 10(-)(12) M. The
      interaction of CDA with the TSA inhibitor has become a paradigm for studying the
      tight TSA binding by enzymes. The formation of the TSA is catalyzed by CDA by a
      mechanism that is similar to the formation of the tetrahedral intermediate during
      the CDA-catalyzed reaction (i.e., through the nucleophilic attack of a Zn
      hydroxide group on C(4)). It is believed that the TSA formed at the active site
      is zebularine 3,4-hydrate. In this paper, it is shown from QM/MM molecular
      dynamics and free energy simulations that zebularine 3,4-hydrate may in fact be
      unstable in the enzyme and that a proton transfer from the Zn-hydroxide group to
      Glu-104 during the nucleophilic attack could be responsible for the very high
      affinity. The nucleophilic attack by the Zn-hydroxide on C(4) is found to be
      concerted with two proton transfers. Such concerted process allows the TSA, an
      alkoxide-like inhibitor, to be stabilized through a mechanism that is similar to
      the transition-state stabilization in the general acid-base catalysis. It is
      suggested that the proton transfer from the Zn-hydroxide to Glu-104, which is
      required to generate the general acid for protonating the leaving ammonia, may
      play an important role in lowering the activation barrier during the catalysis.

PMID- 15740160
TI  - Dimensional effects on the LO-TO splitting in CF4: first-principles and infrared
      absorption studies.
AB  - The development of longitudinal optical-transverse optical (LO-TO) modes in CF(4)
      has been studied experimentally and theoretically as a function of
      dimensionality. Infrared absorption experiments for CF(4) adsorbed on single
      walled carbon nanotubes indicate a lack of LO-TO splitting at low coverage and a
      gradual appearance of LO-TO modes as the coverage of CF(4) on the nanotubes is
      increased. We have performed density functional perturbation theory calculations
      for the vibrational frequencies, IR absorption spectra, and phonon density of
      states for CF(4) in one, two, and three dimensions. The calculations demonstrate
      that LO-TO splitting in 1D is qualitatively different from that computed for 2D
      or the bulk. The magnitude of the splitting in 1D is about one-half that computed
      for the bulk, and the LO mode is very weakly blue-shifted in 1D. We predict that
      the phonon density of states changes dramatically as the dimensionality of the
      crystal is changed. This prediction can be tested experimentally via inelastic
      neutron scattering. We conclude that LO-TO splitting can be used as a probe to
      identify 1D states of matter.

PMID- 15740161
TI  - pi-Stacking in thiophene oligomers as the driving force for electroactive
      materials and devices.
AB  - The pi-stacking between aromatic oligomers has been extensively studied for many
      years, although the notion of exploiting this phenomenon as the driving force for
      molecular actuation has only recently emerged. In this work we examine with MP2
      and Car-Parrinello ab initio calculations the actuation properties of a novel
      class of thiophene-based materials introduced by Swager et al. (Adv. Mater. 2002,
      14, 368; J. Am. Chem. Soc. 2003, 125, 1142). The chemical ingredients of the
      assembly, calix[4]arenes and oligothiophenes, are screened separately to
      characterize the actuation mechanisms and design optimal architectures. In
      particular, ab initio methods are used to study pi-stacking in mixed-valence
      oligothiophene dimers, revealing strong interactions that can be turned on and
      off as a function of the electrochemical potential. We show how these
      interactions could be harnessed to achieve molecular actuation and investigate
      the response of an active unit in real time with first-principles molecular
      dynamics simulations.

PMID- 15740162
TI  - Selective chemical shift assignment of B800 and B850 bacteriochlorophylls in
      uniformly [13C,15N]-labeled light-harvesting complexes by solid-state NMR
      spectroscopy at ultra-high magnetic field.
AB  - The electronic ground states of the bacteriochlorophyll a type B800 and type B850
      in the light-harvesting 2 complex of Rhodopseudomonas acidophila strain 10050
      have been characterized by magic angle spinning (MAS) dipolar (13)C-(13)C
      correlation NMR spectroscopy. Uniformly [(13)C,(15)N] enriched light-harvesting 2
      (LH2) complexes were prepared biosynthetically, while [(13)C,(15)N]-B800 LH2
      complexes were obtained after reconstitution of apoprotein with uniformly
      [(13)C,(15)N]-enriched bacteriochlorophyll cofactors. Extensive sets of isotropic
      (13)C NMR chemical shifts were obtained for each bacteriochlorin ring species in
      the LH2 protein. (13)C isotropic shifts in the protein have been compared to the
      corresponding shifts of monomeric BChl a dissolved in acetone-d(6). Density
      functional theory calculations were performed to estimate ring current effects
      induced by adjacent cofactors. By correction for the ring current shifts, the
      (13)C shift effects due to the interactions with the protein matrix were
      resolved. The chemical shift changes provide a clear evidence for a global
      electronic effect on the B800 and B850 macrocycles, which is attributed to the
      dielectrics of the protein environment, in contrast with local effects due to
      interaction with specific amino acid residues. Considerable shifts of -6.2 <
      Deltasigma < +5.8 ppm are detected for (13)C nuclei in both the B800 and the B850
      bacteriochlorin rings. Because the shift effects for the B800 and B850 are
      similar, the polarization of the electronic ground states induced by the protein
      environment is comparable for both cofactors and corresponds with a red shift of
      approximately 30 nm relative to the monomeric BChl dissolved in acetone-d(6). The
      electronic coupling between the B850 cofactors due to macrocycle overlap is the
      predominant mechanism behind the additional red shift in the B850.

PMID- 15740166
TI  - Healthcare expenditure and ageing: a comment.

PMID- 15740163
TI  - A new spin probe of protein dynamics: nitrogen relaxation in 15N-2H amide groups.
AB  - (15)N spin relaxation data have provided a wealth of information on protein
      dynamics in solution. Standard R(1), R(1)(rho), and NOE experiments aimed at
      (15)N[(1)H] amide moieties are complemented in this work by HA(CACO)N-type
      experiments allowing the measurement of nitrogen R(1) and R(1)(rho) rates at
      deuterated (15)N[(2)D] sites. Difference rates obtained using this approach,
      R(1)((15)N[(1)H]) - R(1)((15)N[(2)D]) and R(2)((15)N[(1)H]) - R(2)((15)N[(2)D]),
      depend exclusively on dipolar interactions and are insensitive to (15)N CSA and
      R(ex) relaxation mechanisms. The methodology has been tested on a sample of
      peptostreptococcal protein L (63 residues) prepared in 50% H(2)O-50% D(2)O
      solvent. The results from the new and conventional experiments are found to be
      consistent, with respect to both local backbone dynamics and overall protein
      tumbling. Combining several data sets permits evaluation of the spectral density
      J(omega(D) + omega(N)) for each amide site. This spectral density samples a
      uniquely low frequency (26 MHz at a 500 MHz field) and, therefore, is expected to
      be highly useful for characterizing nanosecond time scale local motions. The
      spectral density mapping demonstrates that, in the case of protein L, J(omega(D)
      + omega(N)) values are compatible with the Lipari-Szabo interpretation of
      backbone dynamics based on the conventional (15)N relaxation data.

PMID- 15740167
TI  - Calculating society's willingness to pay for a QALY: key questions for
      discussion.

PMID- 15740168
TI  - Observations on health financing reform in the Republic of Georgia, 1996-2002.

PMID- 15740169
TI  - Productivity research and healthcare delivery innovation.
AB  - If a healthcare delivery system is to achieve quality and efficiency,
      participants must be able to measure quality and efficiency. Yet no healthcare
      system in the world - and certainly not the current US system, our main focus -
      measures, reports and acts on such a measure of productivity. This article
      describes the conventional methodology for measuring healthcare productivity and
      the more recent focus on episodes of illness and priority conditions. Specific
      clinical examples of productivity improvement and the many uses of such research 
      for private industry as well as public policy - illustrate why productivity
      research could be considered the 'genome' of healthcare delivery innovation.

PMID- 15740171
TI  - Medicare payment policy and the controversy over hospital cost shifting.
AB  - This article examines (i) the background and debate over cost shifting; (ii)
      hospitals as business institutions that often shift the financial responsibility
      for their costs in the form of differential pricing; and (iii) how the cost
      shifting debate affects and is affected by Medicare. The aim is to gain a better
      understanding of how changes in reimbursement by large government health
      insurance programmes affect hospital behaviour. The article argues that the
      controversy over cost shifting is becoming an increasingly important issue for
      hospitals in the US and their ability (or willingness) to provide uncompensated
      charity care. The issue has also become very important for workers and their
      dependants. This is because workers have shouldered the largest portion of the
      dramatic growth in healthcare costs that have occurred in the US in recent years,
      due in large part to increased cost shifting (or 'sharing of financial
      responsibility') from their employers.

PMID- 15740170
TI  - Listening to the decision makers: sustainability of PBMA in Alberta.
AB  - BACKGROUND: Decision makers within the Calgary Health Region adopted and applied
      programme budgeting and marginal analysis (PBMA) for priority-setting activity
      across major service portfolios within the Region. METHODS: Seventeen in-depth
      qualitative interviews were conducted with senior managers and clinicians to gain
      a user perspective and identify specific areas for process refinement. Data were
      thematically coded and categorised into relevant themes. RESULTS: Key strengths
      included a culture shift in thinking about the need to reallocate resources
      within a fixed funding envelope, whereas a key challenge identified was in
      putting forth genuine disinvestment options. Areas suggested for improvement
      included evoking an incentive system for stakeholder engagement and having a
      mechanism for tracking the effect of resource reallocations. CONCLUSIONS: Both an
      evidence-based approach to priority setting, as well as a way of thinking around
      managing resource scarcity, can be integrated into organisational processes.
      Findings reported in this article will influence further application in Calgary
      and should provide insight for those attempting such activity elsewhere.

PMID- 15740172
TI  - Examining within-country variation of maternity costs in the context of a
      multicountry, multicentre randomised controlled trial.
AB  - Understanding why healthcare costs vary between patients and between health
      facilities is important in guiding health policy decisions as well as in
      research. However, there is no comprehensive framework that analysts commonly use
      for expressing and examining causes of cost variation in the field of healthcare.
      The aim of this study is to better understand the size and causes of within
      country healthcare cost variation, through presenting evidence for size and
      sources of such variations for two countries (Cuba and Thailand) in the context
      of a randomised controlled trial on antenatal care. The article separates total
      costs into their two components: unit costs and health service use. Unit costs
      are further separated into input quantity per patient visit or day, and the
      prices of these resources. The results show that the main determinant of average
      cost is the staffing pattern and productivity, whereas the main determinants of
      health service use include the model of antenatal care being practised and the
      risk status and illnesses suffered by patients. However, variations in inpatient
      health service use between facilities are largely related to unexplainable
      variations in practice between facilities, irrespective of the trial arm. In
      conclusion, cost variations have important implications for the design of
      clinical trials and for policy makers using evidence from trials in planning
      health services and budgets.

PMID- 15740173
TI  - Aggregating public preferences for healthcare: putting theory into practice.
AB  - The aim of this study was to investigate alternative methods for aggregating
      public preferences that may then be used to guide priority-setting decisions in
      healthcare. This involved asking members of the Australian public to assume the
      role of a healthcare planner and to allocate an additional (but fixed) amount of
      healthcare resources across three sets of options: medical/surgical procedures,
      public health programmes and across population groups exhibiting different
      characteristics. Two methods of aggregation were used: rank ordering and what the
      author describes as the 'pie method'. In contrast to conventional social welfare
      functions (that make use of ordinal, non-comparable utility information of
      individual consumers), the methods used in this study allowed for additional
      information on the intensity and the comparability of the preferences. The impact
      of these different methods on aggregation results is investigated. It is argued
      that those decision makers charged with the day-to-day responsibility of engaging
      the general public in resource allocation decision making need to be aware that
      different methods of aggregation can result in different healthcare priorities.
      Implications for researchers, including the impact of different forms of
      information on the formation of social preferences, are also discussed.

PMID- 15740174
TI  - Neurologically presenting Wilson's disease: epidemiology, pathophysiology and
      treatment.
AB  - Wilson's disease is a rare autosomal recessive disease of copper accumulation and
      copper toxicity, due to mutations in the ATP7B gene, which leads to a failure of
      copper excretion in the bile. It presents clinically primarily as liver disease,
      psychiatric disease, neurological disease, or a combination of these. The
      neurological disease is a movement disorder, with abnormalities of speech,
      tremor, incoordination and dystonia being common features. Diagnosis of
      neurologically presenting patients is usually straightforward, with Kayser
      Fleischer rings and a urine copper over 100 microg/day almost invariably present.
      In the treatment of neurologically presenting patients, penicillamine should
      always be avoided, because of the high risk of permanent, drug-induced,
      additional neurological deterioration. A new drug we have developed,
      tetrathiomolybdate, given for 8-16 weeks, in combination with zinc, is our first
      choice for treating these patients. In the absence of availability of
      tetrathiomolybdate, zinc or trientine are the next best choices.

PMID- 15740175
TI  - Prevention of schizophrenia: can it be achieved?
AB  - Schizophrenia is a serious mental disorder with a profound impact on patients,
      their caregivers and society. It is also an expensive disorder to treat, despite
      being relatively rare. In this paper, prevention of schizophrenia is described in
      terms of primary, secondary and tertiary prevention. Schizophrenia is regarded as
      a neurodevelopmental disorder with different phases. Primary prevention
      essentially involves education programmes about the association of obstetric
      complications and the increased risk of schizophrenia. Secondary prevention
      involves intervention at the prodromal phase. We review the literature and
      discuss the evidence relating to intervention in this phase of the illness. Early
      intervention could result in reduction in morbidity and better quality of life
      for the patients and their families. The prodromal phase can now be identified,
      based on current symptoms, with reliability and predictive validity for the risk
      of development of schizophrenia in the following year. We also discuss possible
      risks faced by prodromal patients, such as unnecessary stigmatisation, and the
      role of drug treatment during intervention at this stage. Any recommendation that
      anti-psychotic medications be routinely prescribed in this phase should be
      supported by more research work. Drug and psychosocial intervention is indicated
      as part of tertiary prevention to prevent further disability in the illness.

PMID- 15740177
TI  - Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and
      vomiting: are they all the same?
AB  - Selective serotonin 5-HT(3) receptor antagonists have proven safe and effective
      for the management of postoperative nausea and vomiting. Dolasetron, granisetron,
      ondansetron and tropisetron selectively and competitively bind to 5-HT(3)
      receptors, blocking serotonin binding at vagal afferents in the gut and in the
      regions of the CNS involved in emesis, including the chemoreceptor trigger zone
      and the nucleus tractus solitarii. Despite their shared mechanism of action, 5
      HT(3) receptor antagonists have different chemical structures and exhibit
      differences in receptor binding affinity, dose response and duration of effect.
      Furthermore, although dolasetron, granisetron, ondansetron and tropisetron are
      all extensively metabolised by the cytochrome P450 (CYP) system, different
      components of this system predominate in the metabolism of each of these agents.
      Hence, although these agents are considered equally effective in the overall
      population, their pharmacokinetic and pharmacodynamic differences may explain the
      variability in individual responses to these drugs. This review discusses the
      pharmacological profiles of dolasetron, granisetron, ondansetron and tropisetron,
      and the clinical implications of differences in their profiles.

PMID- 15740176
TI  - Effect of antiepileptic drugs on reproductive endocrine function in individuals
      with epilepsy.
AB  - It is well known that epilepsy, antiepileptic drugs (AEDs), and the reproductive
      system have complex interactions. Fertility is lower in both men and women with
      epilepsy than in the general population. Moreover, reproductive endocrine
      disorders are more common among patients with epilepsy than among the population
      in general. These disorders have been attributed both to epilepsy itself and to
      use of AEDs. The use of the liver enzyme-inducing AEDs phenobarbital, phenytoin
      and carbamazepine increases serum sex hormone-binding globulin (SHBG)
      concentrations in both men and women with epilepsy. Over time, the increase in
      serum SHBG levels leads to diminished bioactivity of testosterone and estradiol,
      which may result in diminished potency in men and menstrual disorders in some
      women, and thus to reduced fertility. Liver enzyme-inducing AEDs also reduce the
      efficacy of oral contraceptives. Valproic acid medication may have effects on
      serum androgen concentrations and it reduces serum follicle stimulating hormone
      levels in men with epilepsy. However, the clinical significance of valproic acid
      related reproductive endocrine changes in men is unknown. On the other hand, in
      women, use of valproic acid appears to be associated with a frequent occurrence
      of reproductive endocrine disorders characterised by polycystic changes in the
      ovaries, high serum testosterone concentrations (hyperandrogenism) and menstrual
      disorders. These disorders are especially common among women who have gained
      weight during valproic acid treatment. There are some discrepancies regarding the
      reported occurrence of reproductive endocrine disorders in women taking valproic
      acid for epilepsy. However, most studies also including patients receiving
      valproic acid for other reasons than epilepsy, and studies in different non
      epileptic animal models, have shown an association between valproic acid
      medication and hyperandrogenism and related reproductive endocrine disorders.
      From a practical point of view, the length of the menstrual cycles and bodyweight
      should be monitored in women with epilepsy after commencement of treatment with
      valproic acid. A serum testosterone assay is helpful in following the possible
      biochemical endocrine changes. Ultrasonography of the ovaries (preferably
      transvaginal) is indicated if clinical assessment and serum testosterone
      measurement imply that there is a clinically significant valproic acid-related
      reproductive endocrine problem. That would be the case if the menstrual cycles
      were irregular or prolonged (usually >35 days) and serum testosterone levels
      elevated, especially with associated weight gain. The endocrine effects of the
      new AEDs have not been widely studied. However, it seems they may offer an
      alternative if reproductive endocrine problems emerge during treatment with the
      older AEDs.

PMID- 15740178
TI  - US FDA-approved disease-modifying treatments for multiple sclerosis: review of
      adverse effect profiles.
AB  - Several disease-modifying agents (DMAs) are approved for the treatment of
      multiple sclerosis, including three interferon (IFN)-beta products, glatiramer
      acetate and mitoxantrone. This article reviews the adverse event profiles of
      these DMAs based on the pivotal phase III trials, and provides practical
      guidelines for managing adverse effects. In general, the most common adverse
      events associated with IFN beta therapy are flu-like symptoms, including fever,
      chills and myalgias, and headache. The flu-like symptoms typically resolve within
      24 hours and may be mitigated by over-the-counter anti-inflammatory agents.
      Adverse events related to glatiramer acetate therapy include injection-site
      reactions and a systemic reaction consisting of flushing, chest tightness,
      palpitation, anxiety or dyspnoea. The systemic reaction is transient (30 seconds
      to 30 minutes) and self-limited. Mitoxantrone may cause nausea, vomiting,
      alopecia, amenorrhoea and myelosuppression; isolated cases of acute leukaemia and
      dose-related cardiotoxicity have been reported in the literature. Longer-term
      tolerability data on mitoxantrone as a treatment for multiple sclerosis are
      needed. It is important for physicians to counsel patients on DMA-related adverse
      effects, most of which are transient and of mild-to-moderate severity. Various
      strategies that can be employed to prevent or manage these adverse effects and
      lessen their impact on the patient are discussed.

PMID- 15740179
TI  - Do antidepressants reduce the burden imposed by depression on employers?
AB  - The ability to perform paid or unpaid work is integral to an individual's quality
      of life. Therefore, we performed a systematic literature review to examine the
      impact of depression and its treatment on occupational outcomes. This review
      found absenteeism from work to be markedly higher among depressed employees and
      productivity to be dramatically undermined by some symptoms of depression. Gaps
      in the published literature point to the need for future economic and clinical
      analyses to include work-related outcomes. Published studies showed that
      antidepressants can enhance work-related outcomes by alleviating affective
      symptoms. However, the pharmacological properties of antidepressants may produce
      differential effects that influence work-related outcomes in other ways. For
      example, TCAs, but not SSRIs, produce sedation and impair cognitive function in
      ways that could undermine work-related outcomes. Formal analyses are required to
      quantify whether the improved social functioning, motivation and vigilance that
      may be associated with some newer antidepressants translate into improved work
      related outcomes. Although few published studies have directly quantified the
      cost benefit of managing depression and associated lost productivity, existing
      studies that directly assessed work-related outcomes have suggested that treating
      depression is cost effective. Gaps in the published literature imply that the
      impact of depression and antidepressants on occupational outcomes has been
      understudied. This reflects, in part, the fact that antidepressant studies
      lasting 4 or 6 weeks are unlikely to capture the impact of treatment on work
      related measures. In addition, the current evidence base is fraught with other
      methodological limitations. The effect of depression on non-paid employment also
      requires further assessment. In conclusion, the efficacy of antidepressants on
      work-related outcomes should be measured in clinical trials that have an adequate
      design and a suitable follow-up period, and included in health technology
      assessments. Until such studies are available, the evidence base supporting the
      use of antidepressants will remain incomplete.

PMID- 15740180
TI  - Pregabalin: as adjunctive treatment of partial seizures.
AB  - Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5
      methylhexanoic acid, possesses anticonvulsant activity. Pregabalin binds with
      high affinity and specificity to voltage-gated calcium channel alpha(2)-delta
      proteins. The putative mechanism of action of the drug is reduced excitatory
      neurotransmitter release caused by binding to the alpha(2)-delta protein,
      resulting in allosteric modulation of P/Q-type voltage-gated calcium channels. In
      three well designed trials, oral pregabalin as adjunctive therapy in patients
      with refractory partial seizures was significantly (p < or = 0.0007) more
      effective than placebo in reducing seizure frequency when administered at dosages
      of 150-600 mg/day (as two or three divided doses). Adjunctive pregabalin produced
      an overall mean 41.3% improvement from baseline in 28-day seizure-free rate in
      four long-term (maximum exposure 1764 days), open-label studies in 1480 patients.
      CNS-related effects (e.g. dizziness and somnolence) were the most frequent dose
      related treatment-emergent adverse events associated with adjunctive pregabalin
      therapy.

PMID- 15740183
TI  - Morphological dynamics of swelling-induced surface patterns in metal-capped
      polymer bilayer.
AB  - We report on the morphological dynamics of surface patterns induced by swelling
      of metal-capped polymer bilayer on a substrate. When the bilayer is subject to
      solvent vapor, the strain is generated in the polymer layer that is confined by
      the substrate and the metal capping layer. An increase in the strain induces the
      development of the stress in the bilayer to deform the lower polymer layer
      perpendicularly to the surface of the bilayer. Isotropic surface wave patterns
      results from the stress relaxation, the wave number of the patterns shows a
      characteristic temporal dependency on the swelling time, such that km(t)
      approximately t(-1/8). This temporal evolution accompanied by the morphological
      dynamics gives smaller value of the growth rate of the characteristic wavelength
      than that of the case of swelling of gel.

PMID- 15740184
TI  - Ab initio-based intermolecular carbon-carbon pair potentials for polycyclic
      aromatic hydrocarbon clusters.
AB  - We derived the carbon-carbon pair potentials for polycyclic aromatic hydrocarbon
      (PAH) clusters, which exhibited a strikingly similar geometry to that of the two
      layer graphite. The binding energy of PAH clusters ranging in size from the
      benzene dimer to the pyrene dimer obtained by ab initio calculations at the MP2
      level was used to extract the pair potentials in the form of the Lennard-Jones
      and Exponential-6 functions. Identical binding energy and equilibrium interlayer
      distance were reproduced by these functions to those calculated by the ab initio
      method. The pair potentials for PAHs yield the same equilibrium C-C distance as
      the known pair potentials for graphite and fullerenes, but nearly twice the well
      depth because of the polarization of the C-H bond.

PMID- 15740185
TI  - A new method for direct calculation of total energy of protein.
AB  - A new scheme is developed for efficient quantum mechanical calculation of total
      energy of protein based on a recently developed MFCC (molecular fractionation
      with conjugate caps) approach. In this scheme, the linear-scaling MFCC method is
      first applied to calculate total electron density of protein. The computed
      electron density is then employed for direct numerical integration in density
      functional theory (DFT) to yield total energy of protein, with the kinetic energy
      obtained by a proposed ansatz. Numerical studies are carried out to calculate
      torsional energies of two polypeptides using this approach and the energies are
      shown to be in good agreement with the corresponding full system DFT calculation.

PMID- 15740186
TI  - Ground- and excited-state diatomic bond lengths, vibrational levels, and
      potential-energy curves from conventional and localized Hartree-Fock-based
      density-functional theory.
AB  - Ground- and excited-state diatomic bond lengths, vibrational levels, and
      potential-energy curves are determined using conventional and localized Hartree
      Fock (LHF)-based density-functional theory. Exchange only and hybrid functionals
      (with various fractions of exchange) are considered, together with a standard
      generalized gradient approximation (GGA). Ground-state bond lengths and
      vibrational wave numbers are relatively insensitive to whether orbital exchange
      is treated using the conventional or LHF approach. Excited-state calculations are
      much more sensitive. For a standard fraction of orbital exchange, N2 and CO
      vertical excitation energies at experimental bond lengths are accurately
      described by both conventional and LHF-based approaches, providing an asymptotic
      correction is present. Excited-state bond lengths and vibrational levels are more
      accurate with the conventional approach. The best quality, however, is obtained
      with an asymptotically corrected GGA functional. For the ground and lowest four
      singlet excited states, the GGA mean absolute errors in bond lengths are 0.006 A
      (0.5%) and 0.011 A (0.8%) for N2 and CO, respectively. Mean absolute errors in
      fundamental vibrational wavenumbers are 49 cm(-1) (2.7%) and 68 cm(-1) (5.0%),
      respectively. The GGA potential-energy curves are compared with near-exact
      Rydberg-Klein-Rees curves. Agreement is very good for the ground and first
      excited state, but deteriorates for the higher states.

PMID- 15740187
TI  - Comparative analysis of local spin definitions.
AB  - This work provides a survey of the definition of electron spin as a local
      property and its dependence on several parameters in actual calculations. We
      analyze one-determinant wave functions constructed from Hartree-Fock and, in
      particular, from Kohn-Sham orbitals within the collinear approach to electron
      spin. The scalar total spin operators S2 and Sz are partitioned by projection
      operators, as introduced by Clark and Davidson, in order to obtain local spin
      operators SASB and SzA, respectively. To complement the work of Davidson and co
      workers, we analyze some features of local spins which have not yet been
      discussed in sufficient depth. The dependence of local spin on the choice of
      basis set, density functional, and projector is studied. We also discuss the
      results of Sz partitioning and show that SzA values depend less on these
      parameters than SASB values. Furthermore, we demonstrate that for small organic
      test molecules, a partitioning of Sz with preorthogonalized Lowdin projectors
      yields nearly the same results as one obtains using atoms-in-molecules
      projectors. In addition, the physical significance of nonzero SASB values for
      closed-shell molecules is investigated. It is shown that due to this problem,
      SASB values are useful for calculations of relative spin values, but not for
      absolute local spins, where SzA values appear to be better suited.

PMID- 15740188
TI  - Microscopic and macroscopic polarization within a combined quantum mechanics and
      molecular mechanics model.
AB  - A polarizable quantum mechanics and molecular mechanics model has been extended
      to account for the difference between the macroscopic electric field and the
      actual electric field felt by the solute molecule. This enables the calculation
      of effective microscopic properties which can be related to macroscopic
      susceptibilities directly comparable with experimental results. By separating the
      discrete local field into two distinct contribution we define two different
      microscopic properties, the so-called solute and effective properties. The solute
      properties account for the pure solvent effects, i.e., effects even when the
      macroscopic electric field is zero, and the effective properties account for both
      the pure solvent effects and the effect from the induced dipoles in the solvent
      due to the macroscopic electric field. We present results for the linear and
      nonlinear polarizabilities of water and acetonitrile both in the gas phase and in
      the liquid phase. For all the properties we find that the pure solvent effect
      increases the properties whereas the induced electric field decreases the
      properties. Furthermore, we present results for the refractive index, third
      harmonic generation (THG), and electric field induced second-harmonic generation
      (EFISH) for liquid water and acetonitrile. We find in general good agreement
      between the calculated and experimental results for the refractive index and the
      THG susceptibility. For the EFISH susceptibility, however, the difference between
      experiment and theory is larger since the orientational effect arising from the
      static electric field is not accurately described.

PMID- 15740189
TI  - The exchange-correlation potential in ab initio density functional theory.
AB  - From coupled-cluster theory and many-body perturbation theory we derive the local
      exchange-correlation potential of density functional theory in an orbital
      dependent form. We show the relationship between the coupled-cluster approach and
      density functional theory, and connections and comparisons with our previous
      second-order correlation potential [OEP-MBPT(2) (OEP-optimized effective
      potential)] [I. Grabowski, S. Hirata, S. Ivanov, and R. J. Bartlett, J. Chem.
      Phys. 116, 4415 (2002)]. Starting from a general theoretical framework based on
      the density condition in Kohn-Sham theory, we define a rigorous exchange
      correlation functional, potential and orbitals. Specifying initially to second
      order terms, we show that our ab initio correlation potential provides the
      correct shape compared to those from reference quantum Monte Carlo calculations,
      and we demonstrate the superiority of using Fock matrix elements or more general
      infinite-order semicanonical transformations. This enables us to introduce a
      method that is guaranteed to converge to the right answer in the correlation and
      basis set limit, just as does ab initio wave function theory. We also demonstrate
      that the energies obtained from this generalized second-order method [OEP-MBPT2
      f] and [OEP-MBPT2-sc] are often of coupled-cluster accuracy and substantially
      better than ordinary Hartree-Fock based second-order MBPT=MP2.

PMID- 15740190
TI  - Calculation of nonadiabatic couplings in density-functional theory.
AB  - This paper proposes methods for calculating the derivative couplings between
      adiabatic states in density-functional theory (DFT) and compares them with each
      other and with multiconfigurational self-consistent field calculations. They are
      shown to be accurate and, as expected, the costs of their calculation scale more
      favorably with system size than post-Hartree-Fock calculations. The proposed
      methods are based on single-particle excitations and the associated Slater
      transition-state densities to overcome the problem of the unavailability of
      multielectron states in DFT which precludes a straightforward calculation of the
      matrix elements of the nuclear gradient operator. An iterative scheme employing
      linear-response theory was found to offer the best trade-off between accuracy and
      efficiency. The algorithms presented here have been implemented for doublet
      doublet excitations within a plane-wave-basis and pseudopotential framework but
      are easily generalizable to other excitations and basis sets. Owing to their
      fundamental importance in cases where the Born-Oppenheimer separation of motions
      is not valid, these derivative couplings can facilitate, for example, the
      treatment of nonadiabatic charge transfers, of electron-phonon couplings, and of
      radiationless electronic transitions in DFT.

PMID- 15740191
TI  - Calculating intensities using effective Hamiltonians in terms of Coriolis-adapted
      normal modes.
AB  - The calculation of rovibrational transition energies and intensities is often
      hampered by the fact that vibrational states are strongly coupled by Coriolis
      terms. Because it invalidates the use of perturbation theory for the purpose of
      decoupling these states, the coupling makes it difficult to analyze spectra and
      to extract information from them. One either ignores the problem and hopes that
      the effect of the coupling is minimal or one is forced to diagonalize effective
      rovibrational matrices (rather than diagonalizing effective rotational matrices).
      In this paper we apply a procedure, based on a quantum mechanical canonical
      transformation for deriving decoupled effective rotational Hamiltonians. In
      previous papers we have used this technique to compute energy levels. In this
      paper we show that it can also be applied to determine intensities. The ideas are
      applied to the ethylene molecule.

PMID- 15740192
TI  - Efficient and accurate approximations to the molecular spin-orbit coupling
      operator and their use in molecular g-tensor calculations.
AB  - Approximations to the Breit-Pauli form of the spin-orbit coupling (SOC) operator
      are examined. The focus is on approximations that lead to an effective quasi-one
      electron operator which leads to efficient property evaluations. In particular,
      the accurate spin-orbit mean-field (SOMF) method developed by Hess, Marian,
      Wahlgren, and Gropen is examined in detail. It is compared in detail with the
      "effective potential" spin-orbit operator commonly used in density functional
      theory (DFT) and which has been criticized for not including the spin-other orbit
      (SOO) contribution. Both operators contain identical one-electron and Coulomb
      terms since the SOO contribution to the Coulomb term vanishes exactly in the SOMF
      treatment. Since the DFT correlation functional only contributes negligibly to
      the SOC the only difference between the two operators is in the exchange part. In
      the SOMF approximation, the SOO part is equal to two times the spin-same orbit
      contribution. The DFT exchange contribution is of the wrong sign and numerically
      shown to be in error by a factor of 2-2.5 in magnitude. The simplest possible
      improvement in the DFT-SOC treatment [Veff(-2X)-SOC] is to multiply the exchange
      contribution to the Veff operator by -2. This is verified numerically in
      calculations of molecular g-tensors and one-electron SOC constants of atoms and
      ions. Four different ways of handling the computationally critical Coulomb part
      of the SOMF and Veff operators are discussed and implemented. The resolution of
      the identity approximation is virtually exact for the SOC with standard auxiliary
      basis sets which need to be slightly augmented by steep s functions for heavier
      elements. An almost as efficient seminumerical approximation is equally accurate.
      The effective nuclear charge model gives results within approximately 10% (on
      average) of the SOMF treatment. The one-center approximation to the Coulomb and
      one-electron SOC terms leads to errors on the order of approximately 5%. Small
      absolute errors are obtained for the one-center approximation to the exchange
      term which is consequently the method of choice [SOMF(1X)] for large molecules.

PMID- 15740193
TI  - Inhomogeneous multiscale dynamics in harmonic lattices.
AB  - We use projection operators to address the coarse-grained multiscale problem in
      harmonic systems. Stochastic equations of motion for the coarse-grained
      variables, with an inhomogeneous level of coarse graining in both time and space,
      are presented. In contrast to previous approaches that typically start with
      thermodynamic averages, the key element of our approach is the use of a
      projection matrix chosen both for its physical appeal in analogy to mechanical
      stability theory and for its algebraic properties. We show that thermodynamic
      equilibrium can be recovered and obtain the fluctuation dissipation theorem a
      posteriori. All system-specific information can be computed from a series of
      feasible molecular dynamics simulations. We recover previous results in the
      literature and show how this approach can be used to extend the quasicontinuum
      approach and comment on implications for dissipative particle dynamics type of
      methods. Contrary to what is assumed in the latter models, the stochastic process
      of all coarse-grained variables is not necessarily Markovian, even though the
      variables are slow. Our approach is applicable to any system in which the coarse
      grained regions are linear. As an example, we apply it to the dynamics of a
      single mesoscopic particle in the infinite one-dimensional harmonic chain.

PMID- 15740194
TI  - A localized basis that allows fast and accurate second-order Moller-Plesset
      calculations.
AB  - We present a method for computing a basis of localized orthonormal orbitals (both
      occupied and virtual), in whose representation the Fock matrix is extremely
      diagonal dominant. The existence of these orbitals is shown empirically to be
      sufficient for achieving highly accurate second-order Moller-Plesset (MP2)
      energies, calculated according to Kapuy's method. This method (which we
      abbreviate KMP2) involves a different partitioning of the n-electron Hamiltonian
      and scales at most quadratically, with potential for linearity, in the number of
      electrons. As such, we believe the KMP2 algorithm presented here could be the
      basis of a viable approach to local-correlation calculations.

PMID- 15740195
TI  - Vibrations in the B4 rhombic structure.
AB  - A double minimum six-dimensional potential energy surface (PES) is determined in
      symmetry coordinates for the most stable rhombic (D2h) B4 isomer in its 1Ag
      electronic ground state by fitting to energies calculated ab initio. The PES
      exhibits a barrier to the D4h square structure of 255 cm(-1). The vibrational
      levels (J=0) are calculated variationally using an approach which involves the
      Watson kinetic energy operator expressed in normal coordinates. The pattern of
      about 65 vibrational levels up to 1600 cm(-1) for all stable isotopomers is
      analyzed. Analogous to the inversion in ammonia-like molecules, the rhombus
      rearrangements lead to splittings of the vibrational levels. In B4 it is the B1g
      (D4h) mode which distorts the square molecule to its planar rhombic form. The
      anharmonic fundamental vibrational transitions of 11B4 are calculated to be
      (splittings in parentheses): G(0)=2352(22) cm(-1), nu1(A1g)=1136(24) cm(-1),
      nu2(B1g)=209(144) cm(-1), nu3(B2g)=1198(19) cm(-1), nu4(B2u)=271(24) cm(-1), and
      nu5(Eu)=1030(166) cm(-1) (D4h notation). Their variations in all stable
      isotopomers were investigated. Due to the presence of strong anharmonic
      resonances between the B1g in-plane distortion and the B2u out-of-plane bending
      modes, the higher overtones and combination levels are difficult to assign
      unequivocally.

PMID- 15740196
TI  - Heterodyned fifth-order 2D-IR spectroscopy of the azide ion in an ionic glass.
AB  - A heterodyned fifth-order infrared pulse sequence has been used to measure a two
      dimensional infrared (2D-IR) spectrum of azide in the ionic glass
      3KNO3:2Ca(NO3)2. By rephasing a two-quantum coherence, a process not possible
      with third-order spectroscopy, the 2D-IR spectra are line narrowed, allowing the
      frequencies, anharmonicities, and their correlations to be measured for the first
      four (nu=0-3) antisymmetric stretch vibrational levels. In this glass, the
      vibrational levels are extremely inhomogeneously broadened. Furthermore, the
      glass shifts the energy of the nu=3 state more than the others, causing an
      inhomogeneous distribution in the anharmonic constants that are partially
      correlated to the inhomogeneous distribution of the fundamental frequency. These
      effects are discussed in light of the strong interactions that exist between the
      charged solute and solvent. Since this is the first example of a heterodyned
      fifth-order infrared pulse sequence, possible cascaded contributions to the
      signal are investigated. No evidence of cascaded signals is found. Compared to
      third-order spectroscopies, fifth-order pulse sequences provide advanced control
      over vibrational coherence and population times that promise to extend the
      capabilities of ultrafast infrared spectroscopy.

PMID- 15740197
TI  - Competition between adiabatic and nonadiabatic fragmentation pathways in the
      unimolecular decay of the ArI2(B) van der Waals complex.
AB  - The competition between vibrational and electronic predissociations of the
      ArI2(B) van der Waals complex has been studied using several dynamical
      computational methods: exact quantum wave-packet propagation, time-dependent
      golden rule, and quasiclassical trajectory with quantum jumps model. Five
      electronic states are considered using recent three-dimensional coupled surfaces
      obtained with a perturbative diatoms-in-molecules method. Final vibrational and
      electronic populations, predissociation rates, and absorption spectra have been
      computed for I2(B,v=18-24)<--I2(X,v=0) excitations within the complex. The
      contribution of vibrational predissociation into the total decay oscillates as a
      function of vibrational excitation due to intramolecular vibrational relaxation
      in a sparse-intermediate regime, which induces irregular variations of the total
      decay rate. Franck-Condon oscillations control the branching ratios of the
      individual electronic predissociation channels. However, since these oscillations
      are out of phase as a function of vibrational excitation, they have limited
      effect on the oscillatory behavior of the total predissociation rate. Comparison
      between exact quantum and perturbative golden rule calculations shows that
      vibrational predissociation has some impact on the electronic predissociation
      process and affects the final electronic distributions. On the contrary,
      vibrational product distributions are not significantly affected by the
      electronic predissociation. A classical description of the ArI2 dynamics provides
      an averaged picture of the competing predissociation processes, being better
      adapted for treating intermolecular vibrational relaxation in the statistical
      limit.

PMID- 15740198
TI  - Laser induced fluorescence and resonant two-photon ionization spectroscopy of jet
      cooled 1-hydroxy-9,10-anthraquinone.
AB  - We carried out laser induced fluorescence and resonance enhanced two-color two
      photon ionization spectroscopy of jet-cooled 1-hydroxy-9,10-anthraquinone (1
      HAQ). The 0-0 band transition to the lowest electronically excited state was
      found to be at 461.98 nm (21,646 cm(-1)). A well-resolved vibronic structure was
      observed up to 1100 cm(-1) above the 0-0 band, followed by a rather broad
      absorption band in the higher frequency region. Dispersed fluorescence spectra
      were also obtained. Single vibronic level emissions from the 0-0 band showed
      Stokes-shifted emission spectra. The peak at 2940 cm(-1) to the red of the origin
      in the emission spectra was assigned as the OH stretching vibration in the ground
      state, whose combination bands with the C=O bending and stretching vibrations
      were also seen in the emission spectra. In contrast to the excitation spectrum,
      no significant vibronic activity was found for low frequency fundamental
      vibrations of the ground state in the emission spectrum. The spectral features of
      the fluorescence excitation and emission spectra indicate that a significant
      change takes place in the intramolecular hydrogen bonding structure upon
      transition to the excited state, such as often seen in the excited state proton
      (or hydrogen) transfer. We suggest that the electronically excited state of
      interest has a double minimum potential of the 9,10-quinone and the 1,10-quinone
      forms, the latter of which, the proton-transferred form of 1-HAQ, is lower in
      energy. On the other hand, ab initio calculations at the B3LYP/6-31G(d,p) level
      predicted that the electronic ground state has a single minimum potential
      distorted along the reaction coordinate of tautomerization. The 9,10-quinone form
      of 1-HAQ is the lowest energy structure in the ground state, with the 1,10
      quinone form lying approximately 5000 cm(-1) above it. The intramolecular
      hydrogen bond of the 9,10-quinone was found to be unusually strong, with an
      estimated bond energy of approximately 13 kcal/mol (approximately 4500 cm(-1)),
      probably due to the resonance-assisted nature of the hydrogen bonding involved.

PMID- 15740199
TI  - Infrared-visible and visible-visible double resonance spectroscopy of 1-hydroxy
      9,10-anthraquinone-(H2O)n (n=1,2) complexes.
AB  - The structures of hydrated 1-hydroxyanthraquinone complexes (1-HAQ), 1
      HAQ(H2O)n=1,2, with intramolecular and intermolecular hydrogen bonding
      interactions were studied using laser spectroscopic methods such as laser induced
      fluorescence, fluorescence-detected infrared, infrared-visible hole burning, and
      visible-visible hole burning spectroscopy. In the 1:1 complex 1-HAQ(H2O)1, the
      water binds to the free carbonyl group of 1-HAQ not associated with
      intramolecular hydrogen bond. The second water in the 1:2 complex, 1-HAQ(H2O)2,
      binds to the first water of the 1:1 complex rather than other hydrogen bonding
      sites of 1-HAQ. A pair of two geometric isomers was produced in a supersonic jet
      for each of the 1:1 and 1:2 complexes. Both isomers of each complex have the same
      vibrational spectra in the region of the OH stretching vibration of water, but
      have different energies for the 0-0 band of vibronic transition due to the
      asymmetry of the two phenyl rings in 1-HAQ. The 0-0 bands for all four species of
      1-HAQ(H2O)n=1,2 were unambiguously assigned by comparing with the results of ab
      initio calculations, which yielded the structures, vibrational frequencies, and
      relative energies of the frontier molecular orbitals.

PMID- 15740200
TI  - Structural and electronic properties of S-doped fullerene C58: where is the S
      atom situated?
AB  - Structural and electronic properties of S-doped fullerene C58 were calculated
      systematically via Hartree-Fock self-consistent field (SCF) and density
      functional B3LYP levels of theory with 6-31G(d) basis set. The most stable C58S
      represents an open cage structure with a nine-member ring orifice, which provides
      a large hole for large atoms or small molecules to pass through into the cage.
      The most stable endohedral S@C58 has the S atom seated near the center of the C58
      cage. The calculated highest occupied molecular orbital-lowest unoccupied
      molecular orbital energy gaps of the isomers lie in the range of 1.42-2.50 eV.
      The electron affinity and the ionization potential were also presented as an
      indicator of the kinetic stability. Our results may aid in the design of
      experimental methods for controlling the nature of fullerene cages (for example,
      doping, opening, and reclosing them).

PMID- 15740201
TI  - Vibration-rotation interactions between overtone and combination levels of
      asymmetric-top molecules: application to the infrared spectroscopy of
      formaldehyde and ketene.
AB  - The conventional vibration-rotation Hamiltonian for an asymmetric-top molecule is
      rewritten by expanding the elements of the inverse inertial tensor about the
      equilibrium molecular geometry. The approach allows the identification of terms
      in the Hamiltonian that couple states differing by two, three, or four
      vibrational quanta and hence the calculation of dimensioned Coriolis xi coupling
      coefficients for interacting fundamental, overtone, and combination levels. The
      matrix elements that result from the application of the expanded Hamiltonian
      depend upon the harmonic vibrational wave numbers, equilibrium moments of
      inertia, Coriolis zeta parameters, and the derivatives of the elements of the
      inertial tensor matrix with respect to each of the normal coordinates. The
      Coriolis coupling coefficients may be calculated through evaluation of the
      summations that result from the appropriate terms. The validity of the approach
      is demonstrated through the calculation of coupling coefficients for interacting
      levels in formaldehyde and ketene. The uncertainty in the calculated values of
      the coupling coefficients is typically better than +/-6%, although the values
      calculated for interactions that involve low-frequency vibrational modes are less
      reliable. Comparisons are made between the calculated values and experimental
      results.

PMID- 15740202
TI  - The dynamics of Br(2Pj) formation in the photodissociation of vinyl and
      perfluorovinyl bromides.
AB  - The photodissociation dynamics of vinyl bromide and perfluorovinyl bromide have
      been investigated at 234 nm using a photofragment ion imaging technique coupled
      with a state-selective [2+1] resonance-enhanced multiphoton ionization scheme.
      The nascent Br atoms stem from the primary C-Br bond dissociation leading to the
      formation of C2H3(X) and Br(2Pj;j=1/2,3/2). The obtained translational energy
      distributions have been well fitted by a single Boltzmann and three Gaussian
      functions. Boltzmann component has not been observed in the perfluorovinyl
      bromide. The repulsive 3A'(n,sigma *) state has been considered as the origin of
      the highest Gaussian components. Middle translational energy components with
      Gaussian shapes are produced from the 1A"(pi,sigma*) and/or 3A"(pi,sigma*) which
      are very close in energy. Low-energy Gaussian components are produced via
      predissociation from the 3A'(pi,pi*) state. The assignments have also been
      supported by the recoil anisotropy corresponding to the individual components. It
      is suggested that intersystem crossing from the triplet states to the ground
      state has been attributed to the Boltzmann component and the fluorination reduces
      the probability of this electronic relaxation process.

PMID- 15740203
TI  - Distant-dipole field in liquids and diffusion: a perturbative approach.
AB  - A perturbative approach is employed to solve the Bloch-Torrey equations in the
      presence of distant-dipole fields in nuclear magnetic resonance. The procedure,
      although only carried out to first order in the perturbation parameter
      a=1/k2Dtaud, could, in principle, be generalized to higher orders. Here D is the
      diffusivity, taud the dipolar demagnetization time, and k is the wave vector of
      the spatial modulation of magnetization produced by the magnetic field gradient.
      The results are especially interesting for dilute binary mixtures consisting of
      molecular species with different diffusivities. In this case the calculated two
      dimensional correlation spectroscopy revamped by asymmetric Z-gradient echo
      detection spectra are shown to be free from some inadequacies resulting from a
      simplistic application of standard approximations.

PMID- 15740204
TI  - Quantum mode-coupling theory for binary mixtures.
AB  - We extend the quantum mode-coupling theory of neat liquids to the case of binary
      mixtures, in order to study supercooled liquids where quantum fluctuations may
      compete with thermal fluctuations. We apply the theory to a generic model of a
      binary mixture of Lennard-Jones particles. Our treatment may be used to study
      quantum aging and exotic glass melting scenarios in structural supercooled
      quantum liquids.

PMID- 15740205
TI  - High-resolution electron spin resonance spectroscopy of XeF* in solid argon. The
      hyperfine structure constants as a probe of relativistic effects in the chemical
      bonding properties of a heavy noble gas atom.
AB  - Xenon fluoride radicals were generated by solid-state chemical reactions of
      mobile fluorine atoms with xenon atoms trapped in Ar matrix. Highly resolved
      electron spin resonance spectra of XeF* were obtained in the temperature range of
      5-25 K and the anisotropic hyperfine parameters were determined for magnetic
      nuclei 19F, 129Xe, and 131Xe using naturally occurring and isotopically enriched
      xenon. Signs of parallel and perpendicular hyperfine components were established
      from analysis of temperature changes in the spectra and from numerical solutions
      of the spin Hamiltonian for two nonequivalent magnetic nuclei. Thus, the complete
      set of components of hyperfine- and g-factor tensors of XeF* were obtained: 19F
      (Aiso=435, Adip=1249 MHz) and 129Xe (Aiso=-1340, Adip=-485 MHz);
      g(parallel)=1.9822 and g(perpendicular)=2.0570. Comparison of the measured
      hyperfine parameters with those predicted by density-functional theory (DFT)
      calculations indicates, that relativistic DFT gives true electron spin
      distribution in the 2Sigma+ ground-state, whereas nonrelativistic theory
      underestimates dramatically the electron-nuclear contact Fermi interaction (Aiso)
      on the Xe atom. Analysis of the obtained magnetic-dipole interaction constants
      (Adip) shows that fluorine 2p and xenon 5p atomic orbitals make a major
      contribution to the spin density distribution in XeF*. Both relativistic and
      nonrelativistic calculations give close magnetic-dipole interaction constants,
      which are in agreement with the measured values. The other relativistic feature
      is considerable anisotropy of g-tensor, which results from spin-orbit
      interaction. The orbital contribution appears due to mixing of the ionic 2Pi
      states with the 2Sigma+ ground state, and the spin-orbit interaction plays a
      significant role in the chemical bonding of XeF*.

PMID- 15740206
TI  - Liquid-vapor equilibrium and surface tension of nonconformal molecular fluids.
AB  - Molecular dynamics simulations at constant temperature have been performed on the
      liquid-vapor interface for fluids characterized by a recently introduced three
      parameter potential. This potential is a modification of the well-known spherical
      Kihara interaction and is termed approximate nonconformal (ANC). It has been used
      successfully to describe many real molecules in the gaseous phase. Besides the
      usual molecular energy and size, the ANC potential introduces a third parameter
      s, called softness, to measure the form of the potential profile. Study of these
      systems shows that their critical and interfacial properties follow very closely
      those of four selected substances: argon, methane, propane, and hexane.
      Deviations of the properties predicted from the experimental values are analyzed
      and their probable causes are determined. The critical properties of ANC fluids
      and their dependence on s are also obtained via first-order perturbation theory
      in the form of an augmented van der Waals model. Analysis of the results shows
      that ANC potential functions can be used as reliable effective interactions for
      real dense fluids.

PMID- 15740207
TI  - Observation of the lead carbonyls, PbnCO(n=1-4): reactions of lead atoms and
      small clusters with carbon monoxide in solid argon.
AB  - Reactions of laser-ablated Pb atoms with CO molecules in solid argon lead to the
      formation of the lead carbonyls, PbnCO (n=1-4), using matrix-isolation infrared
      spectroscopy. Absorption at 2027.7 cm(-1) is assigned to C-O stretching mode of
      the PbCO product, which appears and increases on annealing, disappears on
      broadband irradiation, and recovers on further annealing. Small lead cluster mono
      carbonyls PbnCO (n=2-4) are also observed in the present infrared spectra. Based
      on the results of stepwise annealing and the comparison with theoretical
      predictions, the absorptions at 1915.5, 1923.8, and 2042.8 cm(-1) are assigned to
      Pb2CO, Pb3CO, and Pb4CO, respectively. Bridging CO is found in Pb2CO or Pb3CO,
      whereas terminal CO in Pb4CO. The density functional theory calculations have
      been performed on these molecules and small naked lead clusters. The good
      agreement between experimental and calculated vibrational frequencies, relative
      absorption intensities, and isotopic shifts provides strong support for the
      identifications of these lead mono-carbonyls PbnCO (n=1-4). Furthermore,
      energetic analysis for the possible reactions of lead atoms with CO molecules is
      also given.

PMID- 15740208
TI  - Diffusion, relaxation, and chemical exchange in casein gels: a nuclear magnetic
      resonance study.
AB  - Water in protein/water mixtures can be described in terms of bound water and free
      water, by exchange between these two states, and by its exchange with appropriate
      sites on the protein. 1H-NMR diffusion and relaxation measurements provide
      insights into the mobility of these states. T2 relaxation-time dispersions (i.e.,
      T2 relaxation times at different echo pulse spacings) reveal additional
      information about exchange. We present a comprehensive set of diffusion and T2
      dispersion measurements on casein gels for which the protein/water ratio ranges
      from 0.25 to 0.5. The combination of these methods, taken in conjunction with
      concentration dependence, allows a good estimate of the parameters required to
      fit the data with Luz/Meiboom and Carver/Richards models for relaxation and
      chemical exchange. We compare the exchange (a) between water and protein and (b)
      between free water and bound water. Further, we attempt to distinguish chemical
      site exchange and diffusion/susceptibility exchange.

PMID- 15740209
TI  - Nuclear magnetic resonance and dielectric investigations of molecular motions in
      a glassy crystal: the mixed compound (CN-adm)0.75(Cl-adm)0.25.
AB  - The dynamic properties of plastic crystalline mixed adamantane's derivatives
      namely cyanoadamantane (75%) and chloroadamantane (25%) were investigated by
      dielectric and nuclear magnetic resonance (NMR) spectroscopy, covering a spectral
      range of 12 decades in the temperature range 110-420 K. Phase transformations
      were studied and dynamical parameters of the plastic (I), glassy (Ig), and
      ordered (III) phases were determined and compared with those of pure compounds.
      The dynamics of the supercooled plastic phase is characterized by an alpha
      process exhibiting an Arrhenius behavior which classified the mixed compound as a
      strong glass former. In the plastic phase, NMR relaxation times were interpreted
      by using a Frenkel model, which takes into account structural equilibrium
      positions. This model explains adequately the experimental results by considering
      two molecular motions. In both the glassy state and plastic phase the motional
      parameters agree with those of 1-cyanoadamantane. On the contrary, in the ordered
      phase, the motional parameters related to the uniaxial rotation of
      chloroadamantane molecules indicate an accelerated motion.

PMID- 15740210
TI  - Ab initio molecular dynamics simulation of liquid Al88Si12 alloys.
AB  - First-principles molecular dynamics simulations are carried out to study the
      structures, dynamics, and electronic properties of liquid Al88Si12 in the
      temperature ranging from 898 to 1298 K. The temperature dependence of static
      structure factors, pair correlation functions, and electronic density-of-states
      are investigated. The structural properties obtained from the simulations are in
      good agreement with the x-ray diffraction experimental results.

PMID- 15740211
TI  - Molecular dynamic heterogeneity of confined lipid films by 1H magnetization
      exchange nuclear magnetic resonance.
AB  - The molecular dynamic heterogeneity of monolayer to submonolayer thin lecithin
      films confined to submicron cylindrical pores were investigated by 1H
      magnetization exchange nuclear magnetic resonance. In this experiment a z
      magnetization gradient was generated by a double-quantum dipolar filter. The
      magnetization-exchange decay and buildup curves were interpreted with the help of
      a theoretical model based on the approximation of a one-dimensional spin
      diffusion process in a three-domain morphology. The dynamic heterogeneity of the
      fatty acid chains and the effects of the surface area per molecule, the diameter
      of the pores, and the temperature were characterized with the help of local spin
      diffusion coefficients. The effect of various parameters on the molecular
      dynamics of the mobile region of the fatty acid chains was quantified by
      introducing an ad hoc Gaussian distribution function of the 1H residual dipolar
      couplings. For the lipid films investigated in this study, the surface induced
      order and the geometrical confinement affect the chain dynamics of the entire
      molecule. Therefore, each part of the chain independently reflects the effect of
      surface coverage, pore size, and temperature.

PMID- 15740212
TI  - Stochastic diffusion interactions and coarsening in a system of droplets growing
      from a supersaturated gas mixture.
AB  - In this work we study diffusion interactions among liquid droplets growing in
      stochastic population by condensation from supersaturated binary gas mixture.
      During the postnucleation transient regime collective growth of liquid droplets
      competing for the available water vapor decreases local supersaturation leading
      to the increase of critical radius and the onset of coarsening process. In
      coarsening regime the growth of larger droplets is prevailing noticeably
      broadening the droplet size-distribution function when the condensation process
      becomes more intensive than the supersaturation yield. Modifications in the
      kinetic equation are discussed and formulated for a stochastic population of
      liquid droplets when diffusional interactions among droplets become noteworthy.
      The kinetic equation for the droplet size-distribution function is solved
      together with field equations for the mass fraction of disperse liquid phase,
      mass fraction of water vapor component of moist air, and temperature during
      diffusion-dominated regime of droplet coarsening. The droplet size and mass
      distributions are found as functions of the liquid volume fraction, showing
      considerable broadening of droplet spectra. It is demonstrated that the effect of
      latent heat of condensation considerably changes coarsening process. The
      coarsening rate constant, the droplet density (number of droplets per unit
      volume), the screening length, the mean droplet size, and mass are determined as
      functions of the temperature, pressure, and liquid volume fraction.

PMID- 15740213
TI  - Nematic fluid structure in wall-field geometry.
AB  - We describe an integral equation method for obtaining the distribution of a
      nematic fluid near a wall and interacting with a uniform orienting field.
      Complete density-orientational profiles are calculated for a model nematic with
      different wall-particle interactions and different orientations of the wall with
      respect to the field. For orienting walls we identify particular long-range
      correlations that are responsible for reorientation of the bulk nematic at zero
      external field. These correlations become stronger as the wall-particle
      interaction is increased in range; they become longer ranged as the orienting
      field is weakened. Special attention is focused on systems where the wall
      particle interaction favors orientations perpendicular to the surface. The local
      director orientation can vary discontinuously with the distance from the surface
      when the orienting influences of the field and the wall are antagonistic. At high
      densities smectic-like structures appear. Adsorption phenomena are also
      discussed. For inert hard walls, the ordered fluid avoids the surface, and a
      surface layer where the particles tend to orient perpendicular to the bulk
      director appears. Experimentally, this might be seen as wetting of the wall by a
      less-ordered fluid.

PMID- 15740214
TI  - Molecular dynamics simulation of amphiphilic dimers at a liquid-vapor interface.
AB  - Molecular dynamics simulations are utilized to simulate a model liquid-vapor
      amphiphile system. Amphiphilic surfactant molecules are modeled as dimers
      composed of a hydrophilic head and a hydrophobic tail. Three dimer models with
      three different head sizes and two different head-to-tail size ratios are
      studied. The surfactant molecules distribute preferentially at the interfaces at
      low concentrations and form micelles in the bulk liquid phase as the
      concentration increases. We find that the surface tension decreases as molecular
      concentration increases, with a reduction in the rate of decrease after
      micellization occurs. The extent to which a surfactant can reduce the surface
      tension at a given concentration is found to depend on the head size.
      Furthermore, the head size and concentration dependence of the surfactant tilt
      angle distribution is studied and compared to experimental data.

PMID- 15740215
TI  - The gap between crystalline and osmotic swelling of Na-montmorillonite: a Monte
      Carlo study.
AB  - Although the swelling of clay during moistening is a broadly experienced
      occurrence, the mechanisms driving it and especially the reason for the existence
      of a peculiar gap between crystalline and osmotic swelling of Na-montmorillonite
      are not yet fully understood. We obtained a deeper insight by means of Monte
      Carlo simulations of Na-montmorillonite swelling, which yield the swelling curve,
      interaction energies between and characteristic positions of structural atoms and
      water molecules. We find that a chainlike structure consisting of Na cations,
      water molecules, and oxygens of substituted tetrahedrons of neighboring mineral
      layers is formed in the interlayer space of Na-montmorillonite at a layer spacing
      of approximately 19 A, where experimental investigations show termination of
      crystalline swelling. Such a persistent structure may lock the interlayer space,
      until excess water is able to break this chain by osmotic forces. We suggest that
      its formation is the reason for the existence of a gap in layer spacings between
      approximately 19 and approximately 40 A, which have been named "forbidden" layer
      spacings in experimental studies.

PMID- 15740216
TI  - Novel synthesis of two-dimensional TiS2 nanocrystallites on Au111.
AB  - We describe a novel approach to synthesize two-dimensional nanocrystalline TiS2
      islands on Au111. Ti is deposited by physical vapor deposition at room
      temperature on AuS-covered Au111 surfaces. Subsequent annealing to temperatures
      between 670 K and 800 K leads to the formation of single-layer, triangular TiS2
      islands. These TiS2 nanocrystallites reflect the structure of bulk TiS2, and are
      composed of S-Ti-S stacking units with hexagonally close-packed layers of sulfur
      atoms and titanium occupying the octahedral sites in between. The lattice
      constant of the hexagonal unit cell is 3.45 A. A superlattice with a repeat
      distance of 17.3 A results from the coincidence of five TiS2 units with six Au
      atoms and is observed in scanning tunneling microscopy and low energy electron
      diffraction. The triangular shape of the islands indicates a preference for one
      of the two possible edge terminations. The observation of two island orientations
      rotated by 60 degrees with respect to each other can be attributed to the
      formation of twin-related TiS2 domains. The population of the two different
      island orientations changes during annealing at 800 K indicating a thermodynamic
      preference for one of the possible stacking sequences.

PMID- 15740217
TI  - Photoconductivity and current producing states in molecular semiconductors.
AB  - We present a methodology for computing photocurrent production in molecular
      semiconducting molecules. Our model combines a single-configuration interaction
      picture with the nonequilibrium Green's function approach to compute the current
      response of a molecular semiconducting wire following excitation. We give
      detailed analysis of the essential excitonic, charge transfer, and dipole states
      for poly-(phenylenevinylene) chains of length 32 and 48 repeat units under an
      electric field bias and use this to develop a reduced dimensional tunneling model
      which accounts for chain-length and field-dependent behavior. In this paper, we
      consider the decay of an excited electron/hole state on a molecular wire under
      bias attached to semiconducting leads at either end. We find that the current
      produced by the decay of an excitation depends not only upon the lifetime of the
      state, as given by the imaginary part of its complex eigenvalue, but also upon
      the net charge on terminal ends of the molecule. We also find that weakly bound
      electron/hole charge-transfer pairs can decay into the continuum via field
      induced tunneling and produce a net current whereas excitonic states decay via
      tunneling but give no net current contribution.

PMID- 15740218
TI  - A density-functional theory study of the interaction of N2O with Rh110.
AB  - The adsorption of nitrous oxide, N2O, on a Rh110 surface has been characterized
      by using density-functional theory. N2O was found to bind to the surface in two
      alternative forms. The first, less stable form is tilted with the terminal N atom
      attached to the surface, while the second, more stable form lies horizontally on
      the surface. Adsorption on the on-top site is more stable than that on the bridge
      site. The tilted form remains linear on adsorption, while the horizontal form is
      bent, with the terminal-nitrogen and oxygen atoms pointing towards the surface.
      At lower adsorbate coverage, Theta less than or similar to 1/4 ML (ML-monolayer),
      the adsorption of a few horizontal N2O configurations is dissociative, i.e., N2O-
      >N2(a)+O(a). The N2O-surface interaction is discussed in terms of the electronic
      structure analysis.

PMID- 15740219
TI  - Structures and dynamics of thermosensitive microgel suspensions studied with
      three-dimensional cross-correlated light scattering.
AB  - The structure factors, short- and long-time diffusion coefficients, and
      hydrodynamic interactions of concentrated poly(N-isopropylacryamide) microgel
      suspensions were measured with simultaneous static and dynamic three-dimensional
      cross-correlated light scattering. The data are interpreted through comparison to
      hard sphere theory. The structure factors are known to be described well by the
      hard sphere approximation. When the structure factor is fit to an effective hard
      sphere volume fraction and radius, the diffusion and hydrodynamic interactions
      are also well described by the hard sphere model. We demonstrate that one single
      hard sphere volume fraction is sufficient to describe the microgel structures,
      hydrodynamic interactions, and long- and short-time collective diffusion
      coefficients. This result is surprising because the particle form of the
      microgels at these temperatures is not rigid, but rather "fuzzy" spheres with
      dangling polymer chains.

PMID- 15740220
TI  - Coverage dependence of oxygen decomposition and surface diffusion on rhodium 111:
      a DFT study.
AB  - A systematic study of oxygen adsorption, decomposition and diffusion on Rh111 and
      its dependence on coadsorbed oxygen molecules has been performed using density
      functional theory calculations. First, the bonding strength between metal surface
      and adsorbed oxygen molecules has been studied as a function of initial oxygen
      coverage. The bonding strength decreases with increasing oxygen coverage, which
      points towards a self-inhibition of the adsorption process. The potential energy
      hypersurface (PES) for the dissociation of oxygen molecules adsorbed on a
      threefold fcc position perpendicular to the surface was calculated using a
      combined linear/quadratic synchronous transit method with conjugate gradient
      refinements. The results indicate that a minor amount of oxygen on the surface
      enhances the decomposition of further oxygen molecules, while this process is
      inhibited at higher coverage. Moreover, PES calculations of a single site jump of
      atomic oxygen on rhodium 111 indicate that the activation energy increases as
      well with increasing oxygen coverage. All results are discussed with respect to a
      rhodium based catalytic NOx reduction/decomposition system proposed by Nakatsuji,
      which decomposes nitrogen oxides in oxygen excess.

PMID- 15740221
TI  - Stability boundaries, percolation threshold, and two-phase coexistence for
      polydisperse fluids of adhesive colloidal particles.
AB  - We study the polydisperse Baxter model of sticky hard spheres (SHS) in the
      modified mean spherical approximation (mMSA). This closure is known to be the
      zero-order approximation C0 of the Percus-Yevick closure in a density expansion.
      The simplicity of the closure allows a full analytical study of the model. In
      particular we study stability boundaries, the percolation threshold, and the gas
      liquid coexistence curves. Various possible subcases of the model are treated in
      details. Although the detailed behavior depends upon the particularly chosen
      case, we find that, in general, polydispersity inhibits instabilities, increases
      the extent of the nonpercolating phase, and diminishes the size of the gas-liquid
      coexistence region. We also consider the first-order improvement of the mMSA (C0)
      closure (C1) and compare the percolation and gas-liquid boundaries for the one
      component system with recent Monte Carlo simulations. Our results provide a
      qualitative understanding of the effect of polydispersity on SHS models and are
      expected to shed new light on the applicability of SHS models for colloidal
      mixtures.

PMID- 15740222
TI  - Optical and structural modeling of disclination lattices in carbonaceous
      mesophases.
AB  - An integrated microstructural and optical model for carbonaceous mesophases is
      developed and used to explain the principles that govern the formation and
      stability of experimentally observed disclination lattices. The model is able to
      capture the orientation features of disclination lattices, including the type and
      location of disclination lines, and the orientation field in the mesophase
      matrix. The optical model based on reflection polarized optical microscopy is
      able to replicate all the details observed in actual observations. The typical
      brush figures have the proper distribution, orientation, and intensity. The
      computational predictions offer science-based routes to create and control
      desirable material architectures based on carbonaceous mesophase-carbon fiber
      composites.

PMID- 15740223
TI  - Interpretation of conservative forces from Stokesian dynamic simulations of
      interfacial and confined colloids.
AB  - This paper presents Stokesian dynamics simulations of experiments involving one
      or two charged colloids near either a single charged wall or confined between
      parallel charged walls. Equilibrium particle-particle and particle-wall
      interactions are interpreted from dynamic particle trajectories in simulations
      involving (1) a single particle levitated above a wall, (2) two particles below a
      wall, and (3) two particles confined between two parallel walls. By specifying
      only repulsive electrostatic Derjaguin-Landau-Verwey-Overbeek (DLVO) potentials
      and including multibody hydrodynamics, we successfully recover expected
      potentials in some cases, while anomalous attraction is observed in other cases.
      Attraction inferred in the latter simulations displays quantitative agreement
      with literature measurements when particle dynamics are interpreted using
      reported analyses. Because anomalous attraction is reproduced in simulations
      using only electrostatic repulsive DLVO potentials, our results reveal the one
      dimensional analyses to be invalid for configurations that are inherently
      multidimensional via multibody hydrodynamics. Parameters related to experimental
      sampling of particle dynamics are also found to be critical for obtaining
      accurate potentials. We explain the anomalous attraction in each experiment using
      effective potentials, which can be employed in an a priori fashion to assist the
      confident design of future experiments involving interfacial and confined
      colloids. Ultimately, our findings reveal the importance of dimensionality and
      multibody hydrodynamics for understanding nonequilibrium dynamics of colloids
      near surfaces.

PMID- 15740224
TI  - Functionally relevant protein motions: extracting basin-specific collective
      coordinates from molecular dynamics trajectories.
AB  - Functionally relevant motion of proteins has been associated with a number of
      atoms moving in a concerted fashion along so-called "collective coordinates." We
      present an approach to extract collective coordinates from conformations obtained
      from molecular dynamics simulations. The power of this technique for
      differentiating local structural fluctuations between classes of conformers
      obtained by clustering is illustrated by analyzing nanosecond-long trajectories
      for the response regulator protein Spo0F of Bacillus subtilis, generated both in
      vacuo and using an implicit-solvent representation. Conformational clustering is
      performed using automated histogram filtering of the inter-C(alpha) distances.
      Orthogonal (varimax) rotation of the vectors obtained by principal component
      analysis of these interresidue distances for the members of individual clusters
      is key to the interpretation of collective coordinates dominating each
      conformational class. The rotated loadings plots isolate significant variation in
      interresidue distances, and these are associated with entire mobile secondary
      structure elements. From this we infer concerted motions of these structural
      elements. For the Spo0F simulations employing an implicit-solvent representation,
      collective coordinates obtained in this fashion are consistent with the location
      of the protein's known active sites and experimentally determined mobile regions.

PMID- 15740225
TI  - A dielectric fallacy in inferring Tg of water.
AB  - In a recent analysis, Angell [Annu. Rev. Phys. Chem. 55, 559 (2004)] concluded
      that if water's Tg is assumed to be 160 K, the plot of dielectric loss tangent
      tan delta against T/Tg for unsintered amorphous solid water overlaps the
      corresponding plots for glycerol and propylene carbonate. We point out that such
      an analysis falsifies both dielectrics and molecular kinetics, and is not useful
      for ascertaining Tg.

PMID- 15740226
TI  - Pseudopure state of a twelve-spin system.
AB  - Pseudopure states of a system of twelve interacting spins are experimentally
      demonstrated. The system is a cluster of dipolar-coupled nuclear spins of fully
      labeled (13)C(6)-benzene in a liquid crystalline matrix. At present, this is the
      largest and the most complex composite system where individual quantum states
      have been addressed.

PMID- 15740227
TI  - Charge asymmetry in HD+.
AB  - Expanding the wave functions of the ground and excited states of HD(+) (or pde)
      in terms of spherically symmetric explicitly correlated Gaussian functions with
      preexponential multipliers consisting of powers of the internuclear distance, and
      using the variational method, we performed very accurate nonadiabatic
      calculations of all bound states of this system corresponding to the zero total
      angular momentum quantum number (vibrational states; v=0-22). The total and the
      transition energies obtained agree with the best available calculations. For each
      state we computed the expectation values of the d-p, d-e, and p-e interparticle
      distances. This is the first time these quantities were computed for HD(+) using
      rigorous nonadiabatic wave functions. While up to the v=20 state some asymmetry
      is showing in the d-e and p-e distances, for v=21 and v=22 we observe a complete
      breakdown of the Born-Oppenheimer approximation and localization of the electron
      almost entirely at the deuteron.

PMID- 15740228
TI  - Exact quantum master equation via the calculus on path integrals.
AB  - An exact quantum master equation formalism is constructed for the efficient
      evaluation of quantum non-Markovian dissipation beyond the weak system-bath
      interaction regime in the presence of time-dependent external field. A novel
      truncation scheme is further proposed and compared with other approaches to close
      the resulting hierarchically coupled equations of motion. The interplay between
      system-bath interaction strength, non-Markovian property, and required level of
      hierarchy is also demonstrated with the aid of simple spin-boson systems.

PMID- 15740229
TI  - Conical intersections and semiclassical trajectories: comparison to accurate
      quantum dynamics and analyses of the trajectories.
AB  - Semiclassical trajectory methods are tested for electronically nonadiabatic
      systems with conical intersections. Five triatomic model systems are presented,
      and each system features two electronic states that intersect via a seam of
      conical intersections (CIs). Fully converged, full-dimensional quantum mechanical
      scattering calculations are carried out for all five systems at energies that
      allow for electronic de-excitation via the seam of CIs. Several semiclassical
      trajectory methods are tested against the accurate quantum mechanical results.
      For four of the five model systems, the diabatic representation is the preferred
      (most accurate) representation for semiclassical trajectories, as correctly
      predicted by the Calaveras County criterion. Four surface hopping methods are
      tested and have overall relative errors of 40%-60%. The semiclassical Ehrenfest
      method has an overall error of 66%, and the self-consistent decay of mixing
      (SCDM) and coherent switches with decay of mixing (CSDM) methods are the most
      accurate methods overall with relative errors of approximately 32%. Furthermore,
      the CSDM method is less representation dependent than both the SCDM and the
      surface hopping methods, making it the preferred semiclassical trajectory method.
      Finally, the behavior of semiclassical trajectories near conical intersections is
      discussed.

PMID- 15740230
TI  - Interpolated potential energy surfaces: How accurate do the second derivatives
      have to be?
AB  - A global potential energy surface for the water dimer is constructed using the
      modified Shepard interpolation scheme of Collins et al. According to this
      interpolation scheme, the energy at an arbitrary geometry is expressed as a
      weighted sum of Taylor series expansions from neighboring data points, where the
      energy and derivative data required are obtained from ab initio calculations. For
      some ab initio methods, errors are introduced into the second derivative matrix,
      either by numerical differencing of ab initio energies or numerical integration
      during the ab initio calculation. Therefore, we test the accuracy required of the
      second derivative data by truncation of the exact second derivatives to a series
      of approximate second derivatives, and assess the effect on the results of a
      quantum diffusion Monte Carlo (QDMC) simulation. Our results show that the
      calculated zero-point energy and wave function histograms converge to within the
      numerical uncertainty of the QDMC simulation by inclusion of either three
      significant figures or three decimal places in the second derivatives.

PMID- 15740231
TI  - Improving the orbital-free density functional theory description of covalent
      materials.
AB  - The essential challenge in orbital-free density functional theory (OF-DFT) is to
      construct accurate kinetic energy density functionals (KEDFs) with general
      applicability (i.e., transferability). During the last decade, several linear
      response (LR)-based KEDFs have been proposed. Among them, the Wang-Govind-Carter
      (WGC) KEDF, containing a density-dependent response kernel, is one of the most
      accurate that still affords a linear scaling algorithm. For nearly-free-electron
      like metals such as Al and its alloys, OF-DFT employing the WGC KEDF produces
      bulk properties in good agreement with orbital-based Kohn-Sham (KS) DFT
      predictions. However, when OF-DFT, using the WGC KEDF combined with a recently
      proposed bulk-derived local pseudopotential (BLPS), was applied to semiconducting
      and metallic phases of Si, problems arose with convergence of the self-consistent
      density and energy, leading to poor results. Here we provide evidence that the
      convergence problem is very likely caused by the use of a truncated Taylor series
      expansion of the WGC response kernel. Moreover, we show that a defect in the
      ansatz for the first-order reduced density matrix underlying the LR KEDFs limits
      the accuracy of these KEDFs. By optimizing the two free parameters involved in
      the WGC KEDF, the two-body Fermi wave vector mixing parameter gamma and the
      reference density rho* used in the Taylor expansion, OF-DFT calculations with the
      BLPS can achieve semiquantitative results for nine phases of bulk silicon. These
      new parameters are recommended whenever the WGC KEDF is used to study nonmetallic
      systems.

PMID- 15740232
TI  - A gauge-independent zeroth-order regular approximation to the exact relativistic
      Hamiltonian--formulation and applications.
AB  - A simple modification of the zeroth-order regular approximation (ZORA) in
      relativistic theory is suggested to suppress its erroneous gauge dependence to a
      high level of approximation. The method, coined gauge-independent ZORA (ZORA-GI),
      can be easily installed in any existing nonrelativistic quantum chemical package
      by programming simple one-electron matrix elements for the quasirelativistic
      Hamiltonian. Results of benchmark calculations obtained with ZORA-GI at the
      Hartree-Fock (HF) and second-order Moller-Plesset perturbation theory (MP2) level
      for dihalogens X(2) (X=F,Cl,Br,I,At) are in good agreement with the results of
      four-component relativistic calculations (HF level) and experimental data (MP2
      level). ZORA-GI calculations based on MP2 or coupled-cluster theory with single
      and double perturbations and a perturbative inclusion of triple excitations
      [CCSD(T)] lead to accurate atomization energies and molecular geometries for the
      tetroxides of group VIII elements. With ZORA-GI/CCSD(T), an improved estimate for
      the atomization energy of hassium (Z=108) tetroxide is obtained.

PMID- 15740233
TI  - Multireference second-order perturbation theory: how size consistent is "almost
      size consistent".
AB  - A systematic study of the deviation from size consistency of the multireference
      second-order Moller-Plesset perturbation theory (MRMP2) method is presented. The
      size-consistency error is shown to depend on the number of monomers in a
      supermolecule calculation, size of basis set, number of correlated valence
      electrons, and size of active space. HF, F(2), and N(2) are used as test cases,
      with stretched bonds, to include simple, well-defined multireference character.
      This is essential in ensuring that MRMP2 is being tested as a multireference
      method. It is concluded that the MRMP2 and other multireference perturbation
      theory methods can exhibit significant size-consistency errors, and that the size
      of the error depends on the manner in which the perturbation theory is
      implemented.

PMID- 15740234
TI  - Path integral evaluation of the quantum instanton rate constant for proton
      transfer in a polar solvent.
AB  - The quantum instanton approximation for thermal rate constants, a type of quantum
      transition state theory (QTST), is applied to a model proton transfer reaction in
      liquid methyl chloride developed by Azzouz and Borgis. Monte Carlo path integral
      methods are used to carry out the calculations, and two other closely related
      QTST's, namely, the centroid-density and Hansen-Andersen QTST, are also evaluated
      for comparison using the present path integral approach. A technique is then
      introduced that calculates the kinetic isotope effect directly via thermodynamic
      integration of the rate with respect to hydrogen mass, which has the practical
      advantage of avoiding costly evaluation of the activation free energy. The
      present application to the Azzouz-Borgis problem shows that the above three types
      of QTST provide very similar results for the rate, within 30% of each other,
      which is nontrivial considering the totally different derivations of these QTSTs;
      the latter rates are also in reasonable agreement with some other previous
      results (e.g., obtained via molecular dynamics with quantum transitions), within
      a factor of approximately 2(7) for the H(D) transfer, thus significantly
      diminishing the possible range of the exact rates. In addition, it is revealed
      that a small but nonnegligible inconsistency exists in the parametrization of the
      Azzouz-Borgis model employed in previous studies, which resulted in the large
      apparent discrepancy in the calculated rates.

PMID- 15740235
TI  - Isotropic periodic sum: a method for the calculation of long-range interactions.
AB  - This work presents an accurate and efficient approach to the calculation of long
      range interactions for molecular modeling and simulation. This method defines a
      local region for each particle and describes the remaining region as images of
      the local region statistically distributed in an isotropic and periodic way,
      which we call isotropic periodic images. Different from lattice sum methods that
      sum over discrete lattice images generated by periodic boundary conditions, this
      method sums over the isotropic periodic images to calculate long-range
      interactions, and is referred to as the isotropic periodic sum (IPS) method. The
      IPS method is not a lattice sum method and eliminates the need for a reciprocal
      space sum. Several analytic solutions of IPS for commonly used potentials are
      presented. It is demonstrated that the IPS method produces results very similar
      to that of Ewald summation, but with three major advantages, (1) it eliminates
      unwanted symmetry artifacts raised from periodic boundary conditions, (2) it can
      be applied to potentials of any functional form and to fully and partially
      homogenous systems as well as finite systems, and (3) it is more computationally
      efficient and can be easily parallelized for multiprocessor computers. Therefore,
      this method provides a general approach to an efficient calculation of long-range
      interactions for various kinds of molecular systems.

PMID- 15740236
TI  - Calculations of near-threshold cross sections for photodissociation of CH+ using
      the Lanczos algorithm.
AB  - We combine the Lanczos algorithm with the absorbing-potential method, implemented
      in a discrete variable representation to calculate the near-threshold
      photodissociation cross sections of CH+. The method is iterative, based on a
      continued fraction representation of the Green function and avoids any explicit
      matrix diagonalization. A very good agreement is found with experiment and close
      coupling calculations.

PMID- 15740237
TI  - Quantum reaction rate from higher derivatives of the thermal flux-flux
      autocorrelation function at time zero.
AB  - A quantum theory of thermal reaction rates is presented which may be viewed as an
      extension of the recently developed "quantum instanton" (QI) model [W. H. Miller,
      Y. Zhao, M. Ceotto, and S. Yang, J. Chem. Phys. 119, 1329 (2003)]. It is based on
      using higher derivatives of the flux-flux autocorrelation function C(t) (as given
      by Miller, Schwartz, and Tromp) at t=0 to construct a short time approximation
      for C(t). Tests of this theory on 1d and collinear reactions, both symmetric and
      asymmetric, show it to be more accurate than the original QI model, giving rate
      constants to approximately 5% for a wide range of temperature.

PMID- 15740239
TI  - Excited electronic states of small water clusters.
AB  - The lowest electronic states that are initially formed upon excitation of small
      water clusters having a central water molecule with one stretched OH bond are
      studied with electronic structure methods. It is found that in water dimer,
      trimer, and pentamer the lowest excited singlet and triplet states are each
      nondissociative for stretching of an OH bond that is hydrogen bonded in an
      icelike configuration to a neighboring water molecule. This is in marked contrast
      to the behavior of an isolated gas phase water monomer, where it is well known
      that the lowest excited state is strongly dissociative upon OH stretching. The
      conclusions of this study may serve as a basis to interpret recent experimental
      evidence that suggests a significant lifetime for excited water in irradiated
      thin ice films, and may also have important implications for the behavior of
      excitation of liquid water.

PMID- 15740238
TI  - Comparison of density functionals for energy and structural differences between
      the high- [5T2g:(t2g)4(eg)2] and low- [1A1g:(t2g)6(eg)0] spin states of iron(II)
      coordination compounds. II. More functionals and the hexaminoferrous cation,
      [Fe(NH3)6]2+.
AB  - The ability of different density functionals to describe the structural and
      energy differences between the high- [(5)T(2g):(t(2g))(4)(e(g))(2)] and low-
      [(1)A(1g):(t(2g))(6)(e(g))(0)] spin states of small octahedral ferrous compounds
      is studied. This work is an extension of our previous study of the hexaquoferrous
      cation, [Fe(H(2)O)(6)](2+), [J. Chem. Phys. 120, 9473 (2004)] to include a second
      compound-namely, the hexaminoferrous cation, [Fe(NH(3))(6)](2+)-and several
      additional functionals. In particular, the present study includes the highly
      parametrized generalized gradient approximations (GGAs) known as HCTH and the
      meta-GGA VSXC [which together we refer to as highly parametrized density
      functionals (HPDFs)], now readily available in the GAUSSIAN03 program, as well as
      the hybrid functional PBE0. Since there are very few experimental results for
      these molecules with which to compare, comparison is made with best estimates
      obtained from second-order perturbation theory-corrected complete active space
      self-consistent field (CASPT2) calculations, with spectroscopy oriented
      configuration interaction (SORCI) calculations, and with ligand field theory
      (LFT) estimations. While CASPT2 and SORCI are among the most reliable ab initio
      methods available for this type of problem, LFT embodies many decades of
      empirical experience. These three methods are found to give coherent results and
      provide best estimates of the adiabatic low-spin-high-spin energy difference,
      DeltaE(LH) (adia), of 12 000-13 000 cm(-1) for [Fe(H(2)O)(6)](2+) and 9 000-11
      000 cm(-1) for [Fe(NH(3))(6)](2+). All functionals beyond the purely local
      approximation produce reasonably good geometries, so long as adequate basis sets
      are used. In contrast, the energy splitting, DeltaE(LH) (adia), is much more
      sensitive to the choice of functional. The local density approximation severely
      over stabilizes the low-spin state with respect to the high-spin state. This
      "density functional theory (DFT) spin pairing-energy problem" persists, but is
      reduced, for traditional GGAs. In contrast the hybrid functional B3LYP
      underestimates DeltaE(LH) (adia) by a few thousands of wave numbers. The RPBE GGA
      of Hammer, Hansen, and Norskov gives good results for DeltaE(LH) (adia) as do the
      HPDFs, especially the VSXC functional. Surprisingly the HCTH functionals actually
      over correct the DFT spin pairing-energy problem, destabilizing the low-spin
      state relative to the high-spin state. Best agreement is found for the hybrid
      functional PBE0.

PMID- 15740240
TI  - A general formula for the rate of resonant transfer of energy between two
      electric multipole moments of arbitrary order using molecular quantum
      electrodynamics.
AB  - A general expression is derived for the matrix element for the resonant transfer
      of energy between an initially excited donor species and an acceptor moiety in
      the ground state, with each entity possessing an electric multipole moment of
      arbitrary order. In the quantum electrodynamical framework employed, the coupling
      between the pair is mediated by the exchange of a single virtual photon. The
      probability amplitude found from second-order perturbation theory is a product of
      the electric moments located at each center and the resonant multipole-multipole
      interaction tensor. Using the Fermi golden rule, a general formula for the rate
      of energy transfer is obtained. As an illustration of the efficacy of the theory
      developed, rates of excitation energy exchange are calculated for systems
      interacting through dipole-quadrupole, dipole-octupole, quadrupole-quadrupole,
      and the familiar dipole-dipole coupling. For each of the cases examined, the near
      and far-zone limits of the migration rate are calculated from the result valid
      for all donor-acceptor separations beyond wave function overlap. Expression of
      the octupole contribution to the transfer rate in terms of its irreducible
      components of weights 1 and 3 leads to new features. The octupole weight-1 term
      is found to contribute only when the interaction is retarded, while the dipole
      octupole weight-1 contribution appears as a higher-order correction term to the
      dipole-dipole rate. Order of magnitude estimates are given for the contributions
      of dipole-quadrupole and dipole-octupole terms relative to the leading dipole
      dipole rate for near-, intermediate-, and far-zone separations to further
      understand the role played by higher multipole moments in the transfer of
      excitation and the mechanism dominating the process.

PMID- 15740241
TI  - Resonant transfer of excitation between two molecules using Maxwell fields.
AB  - The matrix element for the resonant transfer of excitation between two molecules
      possessing electric and magnetic multipole moments of arbitrary order is
      calculated using quantum electrodynamical response theory. A prerequisite of the
      method is the functional form for the lth order linear electric and magnetic
      multipole dependent electric displacement and magnetic field operators in the
      neighborhood of a molecule, whose derivation is also given. The initially
      unexcited species is viewed as a test body accepting energy resonantly via
      coupling to the Maxwell fields of the excited multipole source molecule. The
      generalized electric-electric multipole contribution to the matrix element is
      shown to agree with an earlier calculation using time-dependent perturbation
      theory. As an application involving both electric and magnetic terms, the rate of
      excitation transfer between two chiral molecules is computed and found to depend
      on the handedness of each species.

PMID- 15740242
TI  - Polarizabilities and hyperpolarizabilities for the atoms Al, Si, P, S, Cl, and
      Ar: Coupled cluster calculations.
AB  - Accurate static dipole polarizabilities and hyperpolarizabilities are calculated
      for the ground states of the Al, Si, P, S, Cl, and Ar atoms. The finite-field
      computations use energies obtained with various ab initio methods including
      Moller-Plesset perturbation theory and the coupled cluster approach. Excellent
      agreement with experiment is found for argon. The experimental alpha for Al is
      likely to be in error. Only limited comparisons are possible for the other atoms
      because hyperpolarizabilities have not been reported previously for most of these
      atoms. Our recommended values of the mean dipole polarizability (in the order Al
      Ar) are alpha/e(2)a(0) (2)E(h) (-1)=57.74, 37.17, 24.93, 19.37, 14.57, and 11.085
      with an error estimate of +/-0.5%. The recommended values of the mean second
      dipole hyperpolarizability (in the order Al-Ar) are gamma/e(4)a(0) (4)E(h) (
      3)=2.02 x 10(5), 4.31 x 10(4), 1.14 x 10(4), 6.51 x 10(3), 2.73 x 10(3), and 1.18
      x 10(3) with an error estimate of +/-2%. Our recommended polarizability
      anisotropy values are Deltaalpha/e(2)a(0) (2)E(h) (-1)=-25.60, 8.41, -3.63, and
      1.71 for Al, Si, S, and Cl respectively, with an error estimate of +/-1%. The
      recommended hyperpolarizability anisotropies are Deltagamma/e(4)a(0) (4)E(h) (
      3)=-3.88 x 10(5), 4.16 x 10(4), -7.00 x 10(3), and 1.65 x 10(3) for Al, Si, S,
      and Cl, respectively, with an error estimate of +/-4%.

PMID- 15740243
TI  - A theoretical study on the inner-valence photoelectron spectra lying between 21
      and 26 eV of the O2 molecule.
AB  - Ab initio calculations were carried out to study the structures of the
      photoelectron spectra of the O(2) molecule using complete active space self
      consistent field and multireference single and double excitation configuration
      interaction methods. We focused our attention primarily on the inner-valence
      ionized states lying below 26 eV. Vibrational levels were calculated using
      adiabatic potential curves and vibrational wave functions were used to obtain
      Franck-Condon factors. We show that not only discrete vibrational levels of (3)
      (2)Pi(u), but also the continuum of nuclear motion in (1) (2)Sigma(u) (-)
      contribute to the bands of vibrational progression and the broad peak of the
      continuum between 22.5 and 26 eV. Other states with weak intensity lying between
      19 and 26 eV are also discussed.

PMID- 15740244
TI  - Penning ionization electron spectroscopy of C6H6 by collision with He*(2 3 S)
      metastable atoms and classical trajectory calculations: optimization of ab initio
      model potentials.
AB  - The potential energy surface of benzene (C(6)H(6)) with a He*(2(3)S) atom was
      obtained by comparison of experimental data in collision-energy-resolved two
      dimensional Penning ionization electron spectroscopy with classical trajectory
      calculations. The ab initio model interaction potentials for C(6)H(6)+He*(2(3)S)
      were successfully optimized by the overlap expansion method; the model potentials
      were effectively modified by correction terms proportional to the overlap
      integrals between orbitals of the interacting system, C(6)H(6) and He*(2(3)S).
      Classical trajectory calculations with optimized potentials gave excellent
      agreement with the observed collision-energy dependence of partial ionization
      cross sections. Important contributions to corrections were found to be due to
      interactions between unoccupied molecular orbitals and the He*2s orbital. A
      C(6)H(6) molecule attracts a He*(2(3)S) atom widely at the region where pi
      electrons distribute, and the interaction of -80 meV (ca. -1.8 kcal/mol) just
      cover the carbon hexagon. The binding energy of a C(6)H(6) molecule and a He*
      atom was 107 meV at a distance of 2.40 A on the sixfold axis from the center of a
      C(6)H(6) molecule, which is similar to that of C(6)H(6)+Li and is much larger
      than those of the C(6)H(6)+[He,Ne,Ar] systems.

PMID- 15740245
TI  - Structure and energetics of two- and three-dimensional neutral, cationic, and
      anionic gold clusters Au(5< or = n < or =9)Z (Z=0,+/-1).
AB  - Low-energy structures are found on the potential energy surfaces of the neutral,
      cationic, and anionic gold clusters Au(5< or = n < or =9)Z (Z=0,+/-1) and on the
      neutral potential energy surface of Au(9). These structures provide insights on
      the two to three dimensional (2D-->3D) transition in small neutral and charged
      gold clusters. It is demonstrated that the size threshold for the 2D-3D
      coexistence is lower for cationic than neutral gold clusters: the 2D-3D
      coexistence develops for Au(5) (+) and Au(7) (+) on the cationic potential energy
      surfaces while only for Au(9) on the neutral. Two metastable long-lived dianions
      of gold clusters are also reported.

PMID- 15740246
TI  - Ab initio calculations, potential representation and vibrational dynamics of
      He2Br2 van der Waals complex.
AB  - An intermolecular potential energy surface for He(2)Br(2) complex in the ground
      state is calculated at the levels of fourth-order (MP4) Moller-Plesset and
      coupled-cluster [CCSD(T)] approximations, using large-core pseudopotential for Br
      atoms and the aug-cc-pV5Z basis set for He. The surface is characterized by three
      minima and the minimum energy pathways through them. The global minimum
      corresponds to a linear He-Br(2)-He configuration, while the two other ones to
      "police-nightstick" and tetrahedral structures. The corresponding well depths are
      -90.39/-89.18, -81.23/-80.78 and -74.40/-74.02 cm(-1), respectively, at
      MP4/CCSD(T) levels of theory. It is found that results obtained by summing three
      body parametrized HeBr(2) interactions and the He-He interaction are in very good
      accord with the corresponding MP4/CSSD(T) configuration energies of the
      He(2)Br(2). Variational calculations using a sum of three-body interactions are
      presented to study the bound states of the vdW He(2)Br(2) complex. The binding
      energy D(0) and the corresponding vibrationally averaged structure are determined
      for different isomers of the cluster and their comparison with the available
      experimental data is discussed.

PMID- 15740247
TI  - Photoelectron spectroscopy of nickel-benzene cluster anions.
AB  - (Nickel)(n)(benzene)(m) (-) cluster anions were studied by both mass spectrometry
      and anion photoelectron spectroscopy. Only Ni(n)(Bz)(m) (-) species for which n >
      or =m were observed in the mass spectra. No single-nickel Ni(1)(Bz)(m) (-)
      species were seen. Adiabatic electron affinities, vertical detachment energies,
      and second transition energies were determined for (n,m)=(2,1), (2,2), (3,1), and
      (3,2). For the most part, calculations on Ni(n)(Bz)(m) (-) species by B. K. Rao
      and P. Jena [J. Chem. Phys. 117, 5234 (2002)] were found to be consistent with
      our results. The synergy between their calculations and our experiment provided
      enhanced confidence in the theoretically implied magnetic moments of several
      nickel-benzene complexes. The magnetic moments of small nickel clusters were seen
      to be extremely sensitive to immediate molecular environmental effects.

PMID- 15740248
TI  - Molecular beam studies of the F atom reaction with propyne: site specific
      reactivity.
AB  - The dynamics of the F atom reaction with propyne (CH(3)CCH) has been investigated
      using a universal crossed molecular beam apparatus. Two reaction channels have
      been clearly observed: H+C(3)H(3)F and HF+C(3)H(3). The substitution of F for H
      occurs mainly via a complex formation mechanism, producing reaction products with
      some contribution from a direct reaction mechanism. The HF product, however,
      appears to be dominantly forward scattered relative to the F atom beam direction,
      suggesting that the HF formation occurs via a direct abstraction mechanism.
      Branching ratios for the two observed reaction channels are also determined. The
      H formation channel is found to be the major reaction pathway, while the HF
      formation channel is also significant. From the measurements of DF versus HF
      products from the F atom reaction with deuterated propyne, the H atom picked up
      by the F atom in the reaction with normal propyne seems to come mostly from the
      CH(3) group. In addition, the H atom produced in the H atom formation channel
      appears to be mostly from the CH(3) group with some contribution from the CCH
      group.

PMID- 15740249
TI  - Ab initio potential energy and dipole moment surfaces for H5O2 +.
AB  - Full-dimensional ab initio potential energy surface (PES) and dipole moment
      surface (DMS) are reported for H(5)O(2) (+). Tens of thousands of coupled-cluster
      [CCSD(T)] and second-order Moller-Plesset (MP2) calculations of electronic
      energies, using aug-cc-pVTZ basis, were done. The energies were fit very
      precisely in terms of all the internuclear distances, using standard least-square
      procedures, however, with a fitting basis that satisfies permutational symmetry
      with respect to like atoms. The H(5)O(2) (+) PES is a fit to 48 189 CCSD(T)
      energies, containing 7962 polynomial coefficients. The PES has a rms fitting
      error of 34.9 cm(-1) for the entire data set up to 110 000 cm(-1). This surface
      can describe various internal floppy motions, including the H atom exchanges,
      monomer inversions, and monomer torsions. First- and higher-order saddle points
      have been located on the surface and compared with available previous theoretical
      work. In addition, the PES dissociates correctly (and symmetrically) to
      H(2)O+H(3)O(+), with D(e)=11 923.8 cm(-1). Geometrical and vibrational properties
      of the monomer fragments are presented. The corresponding global DMS fit (MP2
      based) involves 3844 polynomial coefficients and also dissociates correctly.

PMID- 15740250
TI  - Origin of the magic numbers of water clusters with an excess electron.
AB  - Electron-bound water clusters [e(-)(H(2)O)(n)] show very strong peaks in mass
      spectra for n=2, 6, 7, and (11), which are called magic numbers. The origin of
      the magic numbers has been an enigma for the last two decades. Although the magic
      numbers have often been conjectured to arise from the intrinsic properties of
      electron-bound water clusters, we attributed them not to their intrinsic
      properties but to the particularly weak stability of the corresponding neutral
      water clusters (H(2)O)(n=2,6,7, and (11)). As the cluster size increases; this
      nonsmooth characteristic feature in stability of neutral water clusters is
      contrasted to the smooth increase in stability of e(-)-water clusters. As the
      magic number clusters have significant positive adiabatic electron affinities,
      their abundant distributions in atmosphere could play a significant role in
      atmospheric thermodynamics.

PMID- 15740251
TI  - A theoretical study of bond selective photochemistry in CH2BrI.
AB  - Bromoiodomethane photodissociation in the low-lying excited states has been
      characterized using unrestricted Hartree-Fock, configuration-interaction-singles,
      and complete active space self-consistent field calculations with the SDB-aug-cc
      pVTZ, aug-cc-pVTZ, and 3-21g** basis sets. According to the results of the
      vertical excited energies and oscillator strengths of these low-lying excited
      states, bond selectivity is predicted. Subsequently, the minimum energy paths of
      the first excited singlet state and the third excited state for the dissociation
      reactions were calculated using the complete active space self-consistent field
      method with 3-21g** basis set. Good agreement is found between the calculations
      and experimental data. The relationships of excitations, the electronic
      structures at Franck-Condon points, and bond selectivity are discussed.

PMID- 15740252
TI  - Mass-analyzed threshold ionization spectroscopy of the rotamers of p-n
      propylphenol cations and configuration effect.
AB  - Two-color resonant two-photon mass-analyzed threshold ionization (MATI)
      spectroscopy was used to record the vibrationally resolved cation spectra of the
      selected rotamers of p-n-propylphenol. The adiabatic ionization energies of the
      trans, gauche-A, and gauche-B rotamers are determined to be 65 283+/-5, 65 385+/
      5, and 65 369+/-5 cm(-1), which are less than that of phenol by 3342, 3240, and
      3256 cm(-1), respectively. This suggests that the n-propyl substitution causes a
      greater degree in lowering the energy level in the cationic than the neutral
      ground state. Analysis on the MATI spectra of the selected rotamers of p-n
      propylphenol cation shows that the relative orientation of the p-n-alkyl group
      has little effect on the in-plane ring vibrations. However, the low-frequency
      C(3)H(7) bending vibrations appear to be active only for the two gauche forms of
      the cation.

PMID- 15740253
TI  - Separation of quadrupolar and chemical/paramagnetic shift interactions in two
      dimensional 2H (I=1) nuclear magnetic resonance spectroscopy.
AB  - A novel two-dimensional (2)H (spin I=1) nuclear magnetic resonance technique is
      introduced for determination of both quadrupole and chemical/paramagnetic shift
      tensors and their relative orientation. The new method is based upon the well
      known quadrupolar-echo experiment and is designed to refocus the quadrupolar
      interaction at the end of the t(1) evolution period while retaining the
      modulation introduced by the shift interaction. As a result, a projection of the
      resulting two-dimensional spectrum onto its F(1) dimension yields a shift
      anisotropy powder lineshape free from any quadrupolar broadening. The
      chemical/paramagnetic shifts appear in both F(1) and F(2) dimensions and are thus
      spread along a +1 frequency gradient; hence, a projection orthogonal to this
      gradient yields the pure quadrupolar powder lineshape, free from all shift
      interaction effects. The relative orientation of the quadrupole and shift tensors
      can be obtained by analysis of the full two-dimensional correlation lineshape.
      Unlike the well-known double-quantum experiment, the new method is, in principle,
      equally effective for all values of the quadrupolar splitting, including zero.
      The properties of the new technique are demonstrated using computer simulation
      and methods for the extraction of quadrupole and shift tensor parameters are
      described. The new technique is applied to (diamagnetic) benzoic acid-d(1)
      (C(6)H(5)CO(2)D) and (paramagnetic) copper(II) chloride dihydrate-d(4)
      (CuCl(2).2D(2)O).

PMID- 15740254
TI  - Quantum chemical study of the electronic structure of NiCH2 + in its ground state
      and low-lying electronic excited states.
AB  - The electronic structure of NiCH(2) (+), representative of transition metal
      carbene ions, is investigated by means of several methods of quantum chemistry.
      The relative stabilities of the four low-lying doublet electronic states
      ((2)A(1), (2)A(2), (2)B(1), and (2)B(2)) are determined at the coupled cluster
      singles and doubles level (CCSD) and triples level [CCSD(T) and CCSDT-3] with
      both a Hartree-Fock and density functional theory (Kohn-Sham) reference. The
      equation-of-motion coupled cluster for treatment of excited states in singles and
      doubles approximation (EOM-CCSD) is used to characterize the transition energies
      from the (2)A(1) electronic ground state to the low-lying doublet excited states.
      The (2)A(2) and (2)B(1) states are nearly degenerate, found to be separated by
      940 cm(-1) at the EOM-CCSD level, in agreement with the CASSCF energy ordering.
      The (2)B(2) state is calculated to be higher in energy by more than 1.0 eV. The
      spin purity of the low-lying doublet and quadruplet states described by CCSD
      calculations based on the unrestricted open-shell Hartree-Fock reference is
      discussed.

PMID- 15740255
TI  - Vibrational overtone spectroscopy of jet-cooled methanol from 5000 to 14 000 cm(
      1).
AB  - Spectra of jet-cooled methanol in the overtone and combination region from 5000
      to 14 000 cm(-1) have been obtained by means of infrared laser-assisted
      photofragment spectroscopy. Many of the observed features are assigned to
      combination bands of the type nnu(1)+nu(6), nnu(1)+nu(8), and nnu(1)+nu(6)+nu(8)
      (n=1,2,3), where nu(1) is the OH stretch, nu(6) is the OH bend, and nu(8) is the
      CO stretch. These bands show sharp torsion-rotation structure with features as
      narrow as 0.1 cm(-1). We also observe CH stretch overtones that are weaker than
      the OH containing combination bands and lack distinct torsion-rotation structure
      above v(CH)=2. The extent of observed structure on these bands allows us to place
      limits on the intramolecular vibrational energy redistribution decay rates in the
      upper vibrational states. We report a global fit of the observed band centers to
      a simple expression involving low-order anharmonicity constants.

PMID- 15740256
TI  - Cyclic-N3. II. Significant geometric phase effects in the vibrational spectra.
AB  - An accurate theoretical prediction of the vibrational spectra for a pure nitrogen
      ring (cyclic-N(3)) molecule is obtained up to the energy of the (2)A(2)/(2)B(1)
      conical intersection. A coupled-channel approach using the hyperspherical
      coordinates and the recently published ab initio potential energy surface [D.
      Babikov, P. Zhang, and K. Morokuma, J. Chem. Phys. 121, 6743 (2004)] is employed.
      Two independent sets of calculations are reported: In the first set, the standard
      Born-Oppenheimer approximation is used and the geometric phase effects are
      totally neglected. In the second set, the generalized Born-Oppenhimer
      approximation is used and the geometric phase effects due to the D(3h) conical
      intersection are accurately treated. All vibrational states are analyzed and
      assigned in terms of the normal vibration mode quantum numbers. The magnitude of
      the geometric phase effect is determined for each state. One important finding is
      an unusually large magnitude of the geometric phase effects in the cyclic-N(3):
      it is approximately 100 cm(-1) for the low-lying vibrational states and exceeds
      600 cm(-1) for several upper states. On average, this is almost two orders of
      magnitude larger than in the previously reported studies. This unique example
      suggests a favorable path to experimental validation.

PMID- 15740257
TI  - Polarization effects and charge separation in AgCl-water clusters.
AB  - Structural, energetic, vibrational, and electronic properties of salt ion pairs
      (AgCl and NaCl) in water (W) clusters were investigated by density functional
      theory. In agreement with recent theoretical studies of NaCl-water clusters,
      structures where the salt ion pair is separated by solvent molecules or solvent
      separated ion pair (SSIP) were found in AgCl-W(6) and AgCl-W(8) aggregates. Our
      results indicate that for small AgCl-water clusters, contact ion pair (CIP)
      structures are energetically more stable than SSIP, whereas an opposite tendency
      was observed for NaCl-water clusters. In comparison with CIP, SSIP are
      characterized by extensive electronic density reorganization, reflecting enhanced
      polarization effects. A major difference between AgCl-water and NaCl-water CIP
      aggregates concerns charge transfer. In AgCl-water CIP clusters, charge is
      transferred from the solvent (water) to the ion pair. However, in NaCl-water CIP
      clusters charge is transferred from the ion pair to the water molecules. The
      electronic density reorganization in the aggregates was also discussed through
      the analysis of electronic density difference isosurfaces. Time dependent density
      functional theory calculations show that upon complexation of AgCl and NaCl with
      water molecules, excitation energies are significantly blueshifted relative to
      the isolated ion pairs ( approximately 2 eV for AgCl-W(8) SSIP). In keeping with
      results for NaI-water clusters [Peslherbe et al., J. Phys. Chem. A 104, 4533
      (2000)], electronic oscillator strengths of transitions to excited states are
      weaker for SSIP than for CIP structures. However, our results also suggest that
      the difference between excitation energies and oscillator strengths of CIP and
      SSIP structures may decrease with increasing cluster size.

PMID- 15740258
TI  - Electronic structure of the calcium monohydroxide radical.
AB  - Effective valence shell Hamiltonian H(v) calculations are used to map out three
      dimensional potential energy surfaces for the 12 lowest electronic states of the
      CaOH radical. Excitation energies and spectroscopic constants are compared with
      experiment and prior computations where available, but many previously
      unavailable data are provided, including excited state dipole moments and
      oscillator strengths. Particular attention is paid to clarify the nature of
      nonlinear and quasilinear excited states, Renner-Teller couplings, and state
      mixings. The F (2)Pi and G (2)Pi (6 (2)A(') and 8 (2)A(')) states are both found
      to possess nonlinear local minima, due to an avoided crossing. Attention is also
      focused on the characteristics of basis sets necessary in high-accuracy
      calculations for the CaOH radical.

PMID- 15740259
TI  - The dissociation dynamics of He...I 35Cl(B,v'=2,3) complexes with varying amounts
      of internal energy.
AB  - The He...I (35)Cl intermolecular vibrational levels with n'=0-6 that are bound
      within the He+ICl(B,v'=3) potential [A. B. McCoy, J. P. Darr, D. S. Boucher, P.
      R. Winter, M. D. Bradke, and R. A. Loomis, J. Chem. Phys. 120, 2677 (2004)] are
      identified in laser-induced fluorescence experiments performed at very low
      temperatures within a supersonic expansion. Comparisons of the positions and
      intensities of these lines with the excitation spectra, calculated using
      potential surfaces to describe the interactions between the helium atom and ICl
      in its ground and excited state, assist in the assignments. Based on these
      comparisons the excited state potential was rescaled so that the experimental and
      calculated J'=0 energies agree to within the experimental uncertainties for all
      but the lowest, n'=0, intermolecular level. Two-laser, action, and pump-probe
      spectroscopy experiments indicate that the bound He...I (35)Cl(B,v'=3)
      intermolecular vibrational levels undergo vibrational predissociation forming
      rotationally excited I (35)Cl(B,v'=2,j') products with distributions that depend
      upon the initial intermolecular vibrational level excited. Action spectra
      recorded in the ICl B-X, 2-0 region while monitoring the Deltav=0, I
      (35)Cl(B,v'=2) channel reveal two additional dissociation mechanisms for the
      He...I (35)Cl(B,v') excited state complexes: rotational predissociation of
      discrete metastable states lying slightly above the He+I (35)Cl(B,v'=2) asymptote
      and direct dissociation that occurs when the linear conformer is excited to the
      continuum of states above the same asymptote. The rotational predissociation
      pathway forms I (35)Cl(B,v'=2,j') products in all of the rotational states
      energetically accessible. The direct dissociation mechanism yields very cold
      rotational product state distributions; for instance, the average rotational
      energy in the product state distribution measured when the linear complexes are
      prepared 20 cm(-1) above the dissociation limit is only 1.51 cm(-1), representing
      only 7.6% of the available energy.

PMID- 15740260
TI  - Molecular dynamics simulations of cluster nucleation during inert gas
      condensation.
AB  - Molecular dynamics simulations of vapor-phase nucleation of germanium in an argon
      atmosphere were performed and a unexpected channel of nucleation was observed.
      This channel, vapor-induced cluster splitting, is important for more refractory
      materials since the critical nucleus size can fall below the size of a dimer. As
      opposed to conventional direct vapor nucleation of the dimer, which occurs by
      three-body collisions, cluster-splitting nucleation is a second-order reaction.
      The most important cluster-splitting reaction is the collision of a vapor atom
      and a trimer that leads to the formation of two dimers. The importance of the
      cluster-splitting nucleation channel relative to the direct vapor nucleation
      channel is observed to increase with decreasing vapor density and increasing
      ratio of vapor to carrier gas atoms.

PMID- 15740261
TI  - Electron tunneling dynamics in anharmonic bath.
AB  - Tunneling transition probability for a particle interacting with an anharmonic
      bath is found in a time-dependent Hartree approximation. The general expression
      is presented in terms of medium Keldysh functions that are assumed to be known.
      Furthermore, the transition probability is calculated in the noninteracting-blip
      approximation where the rate constant does not exhibit an activation dependence
      at high temperatures. The reorganization energy E(r) and the renormalized
      reaction heat epsilon are expressed in terms of the correlation matrix for a
      solvent and internal modes in both quantum and classical regimes. It is shown
      that E(r) and epsilon are temperature dependent.

PMID- 15740262
TI  - On the microscopic theory of polar solvation dynamics.
AB  - A microscopic model of the time-resolved Stokes shift is developed. The model
      calculates the solvation dynamics by combining the atomic resolution of the
      solute structure with dipolar dynamics from the polarization structure factors of
      the homogeneous solvent. Calculations are made for coumarin 153 and quinoxaline
      optical dyes with atomic geometries and charge distributions taken from quantum
      calculations. Stokes shift dynamics is calculated and compared to experiment in
      high-temperature acetonitrile and methanol and in low-temperature 2-methyl
      tetrahydrofurane using dielectric relaxation data from experiment.

PMID- 15740263
TI  - Calculation of crystal and molecular structures of carbon disulfide CS2.
AB  - Crystal and molecular structures of carbon disulfide CS(2) were investigated by
      molecular packing analysis with a computed dynamical model. This model includes
      thermal motions, molecular deformations, and anisotropic atomic repulsive
      interactions. Several crystalline structures with orthorhombic symmetry Cmca have
      been found by the calculation. The lowest energy structure agrees with the
      experimental one. The temperature dependence of the crystal structure parameters
      reproduces the general features and the particular increase with decreasing
      temperature of the lattice parameter c (and orientational angle psi) as
      determined by x-ray diffraction or neutron scattering experiments. The pressure
      behavior of the crystal structure parameters up to 12 GPa at room temperature is
      also correctly reproduced.

PMID- 15740264
TI  - An application of the novel quantum mechanical/molecular mechanical method
      combined with the theory of energy representation: An ionic dissociation of a
      water molecule in the supercritical water.
AB  - A novel quantum chemical approach recently developed has been applied to an ionic
      dissociation of a water molecule (2H(2)O-->H(3)O(+)+OH(-)) in ambient and
      supercritical water. The method is based on the quantum mechanical/molecular
      mechanical (QM/MM) simulations combined with the theory of energy representation
      (QM/MM-ER), where the energy distribution function of MM solvent molecules around
      a QM solute serves as a fundamental variable to determine the hydration free
      energy of the solute according to the rigorous framework of the theory of energy
      representation. The density dependence of the dissociation free energy in the
      supercritical water has been investigated for the density range from 0.1 to 0.6
      g/cm(3) with the temperature fixed at a constant. It has been found that the
      product ionic species significantly stabilizes in the high density region as
      compared with the low density. Consequently, the dissociation free energy
      decreases monotonically as the density increases. The decomposition of the
      hydration free energy has revealed that the entropic term (-TDeltaS) strongly
      depends on the density of the solution and dominates the behavior of the
      dissociation free energy with respect to the variation of the density. The
      increase in the entropic term in the low density region can be attributed to the
      decrease in the translational degrees of freedom brought about by the aggregation
      of solvent water molecules around the ionic solute.

PMID- 15740265
TI  - Cooling rate dependence of specific heat in systems out of equilibrium.
AB  - The anomaly of specific heat in systems out of equilibrium, especially the
      measurement procedure dependence of specific heat, is investigated by means of
      free energy landscape. Introducing measurement procedure which is based on
      experimental method, we propose a calculation method of specific heat in systems
      out of equilibrium and find an abrupt change in specific heat between annealed
      and quenched states. For longer observation time the change in specific heat
      occurs at lower temperature and becomes sharper. For slower cooling of a system
      the transition temperature becomes lower. This cooling rate dependence of the
      transition temperature is consistent with experiments and thus the abrupt change
      in specific heat can be regarded as the glass transition which is thermally
      identified.

PMID- 15740266
TI  - Dynamics of circular hydrogen bond array in calix[4]arene in a nonpolar solvent:
      a nuclear magnetic resonance study.
AB  - Hydroxyl groups on the lower rim of calix[4]arene form a circular array of four
      equivalent hydrogen bonds. The rate constants of reversal of the array in the
      temperature range of 221-304 K were determined by means of the NMR measurements
      of quaternary (13)C nuclear spin transverse relaxation dependence on the
      effective radio frequency field. The flip-flop rate constants are in the range of
      1.4 x 10(2)-4.2 x 10(4) s(-1), the activation enthalpy is 36.8 kJ/mol, the
      activation entropy is -36 J mol(-1) K(-1). This process was found uncorrelated
      with conformational transition cone-inverted cone, which is about thousand times
      slower. Molecular tumbling of calix[4]arene measured using (13)C spin relaxation
      was found isotropic with correlation times lying in the range of 0.1-3 ns and
      with the activation energy of 21 kJ/mol. In order to assess relaxation of (13)C
      aromatic nuclei, their principal components of chemical shift tensor were
      calculated using the density functional theory approach.

PMID- 15740267
TI  - Cluster formation in two-Yukawa fluids.
AB  - We present a different and efficient method for implementing the analytical
      solution of Ornstein-Zernike equation for two-Yukawa fluids in the mean spherical
      approximation. We investigate, in particular, the conditions for the formation of
      an extra low-Q peak in the structure factor, which we interpret as due to cluster
      formation in the two-Yukawa fluid when the interparticle potential is composed of
      a short-range attraction and a long-range repulsion. We then apply this model to
      interpret the small angle neutron scattering data for protein solutions at
      moderate concentrations and find out that the presence of a peak centered at Q=0
      (zero-Q peak) besides the regular interaction peak due to charged proteins
      implies an existence of long-range attractive interactions besides the charge
      repulsion.

PMID- 15740268
TI  - Extended-range order, diverging static length scales, and local structure
      formation in cold Lennard-Jones fluids.
AB  - We report molecular-dynamics simulations on a three-dimensional, two-component
      Lennard-Jones fluid. We used 125 000 particles (equal numbers of A and B) at
      density N/V=1.29 and 34 temperatures T covering 5 x 10(4) > or =T > or =0.56. The
      pair potential was 4epsilon[(sigma(ij)/r)(12)-(sigma(ij)/r)(6)] with sigma(AA)=1,
      sigma(AB)=11/12, and sigma(BB)=5/6. We computed specific and generic radial
      distribution functions g(ij)(r), and several density-momentum dynamic correlation
      functions whose static (t=0) parts vanish by symmetry. Evidence is presented that
      our systems were adequately annealed to eliminate remnant initial order and were
      adequately equilibrated at each temperature. Static spatial correlations in cold
      Lennard-Jones liquids have longer ranges than are often reported: g(r)-1 unequal
      to 0 is found out to r > or =7 at T=2 and out to r > or =10 at T=0.56. |g(r)-1|
      has an envelope function that simultaneously fits both crests and troughs of
      g(r). The envelope function implies a temperature-dependent static length scale
      l(1); over (0.56 < or =T< or =100), l(1) approximately T(-0.3), contrary to
      suggestions that g(r) is temperature independent as the glass is approached. The
      highest-melting-point crystal that we identified melts at T(m) approximately
      1.08. In the fluid phase, we observe short-range noncrystalline local structure
      formation in g(r) as the glass is approached. Local structure is only found below
      a local structure melting temperature T(mc)=2.0. Local structure vanishes above
      T=2. Local structure becomes more pronounced as temperature is reduced. However,
      at all temperatures at which there is local structure in g(r), the local
      structure is confined to r < or =4. Within the region r < or =4, the amplitude of
      the local structure diminishes with distance r from the central atom
      approximately as exp(-r/l(2)), thereby defining a second distance scale in the
      fluid. l(2), while more difficult to measure, appears to scale with temperature
      as l(2) approximately T(-0.6); l(2) is not the same as l(1). The static and
      dynamic properties of the local structure match properties assigned by Kivelson's
      glass model [S. A. Kivelson et al., J. Chem. Phys. 101, 2391 (1994)] to that
      model's frustration-limited local clusters.

PMID- 15740269
TI  - A femtosecond study of the infrared-driven cis-trans isomerization of nitrous
      acid (HONO).
AB  - We investigate the dynamics and mechanism of the IR-driven cis-trans
      isomerization of nitrous acid (HONO) in a low-temperature krypton matrix applying
      ultrafast time resolved IR spectroscopy. After excitation of the OH-stretching
      mode the trans HONO state decays biexponentially on a 8 and 260 ps time scale.
      The initially excited cis HONO state decays on a 20 ps time scale. Cis HONO
      isomerizes with 10% quantum yield on a 20 ps time scale to trans HONO. The
      quantum yield we observe is significantly smaller than the previously reported
      100%, which could imply that additional, much slower reaction channels exist. We
      furthermore developed a four-dimensional model of the system, which includes the
      three proton intramolecular degrees of freedom of HONO fully quantum mechanically
      and one intermolecular translational degree of freedom of the molecule in the
      crystal cage. We find that cis-trans isomerization necessarily is accompanied by
      a translation of the molecule as a whole in the crystal cage. The translational
      degree of freedom tunes the intramolecular proton states of HONO with respect to
      each other. When resonances occur, the proton states might couple and transfer
      population. We suggest a possible reaction pathway, where the cis OH-stretch
      excited state first couples to a high cis torsional mode, which then may transfer
      almost instantaneously to the trans side. The model qualitatively explains all
      experimental observations.

PMID- 15740270
TI  - A molecular dynamics computer simulation study of room-temperature ionic liquids.
      I. Equilibrium solvation structure and free energetics.
AB  - Solvation in 1-ethyl-3-methylmidazolium chloride and in 1-ethyl-3
      methylimidazolium hexafluorophosphate near equilibrium is investigated via
      molecular dynamics computer simulations with diatomic and benzenelike molecules
      employed as probe solutes. It is found that electrostriction plays an important
      role in both solvation structure and free energetics. The angular and radial
      distributions of cations and anions become more structured and their densities
      near the solute become enhanced as the solute charge separation grows. Due to the
      enhancement in structural rigidity induced by electrostriction, the force
      constant associated with solvent configuration fluctuations relevant to charge
      shift and transfer processes is also found to increase. The effective polarity
      and reorganization free energies of these ionic liquids are analyzed and compared
      with those of highly polar acetonitrile. Their screening behavior of electric
      charges is also investigated.

PMID- 15740271
TI  - A molecular dynamics computer simulation study of room-temperature ionic liquids.
      II. Equilibrium and nonequilibrium solvation dynamics.
AB  - The molecular dynamics (MD) simulation study of solvation structure and free
      energetics in 1-ethyl-3-methylimidazolium chloride and 1-ethyl-3
      methylimidazolium hexafluorophosphate using a probe solute in the preceding
      article [Y. Shim, M. Y. Choi and H. J. Kim, J. Chem. Phys. 122, 044510 (2005)] is
      extended to investigate dynamic properties of these liquids. Solvent fluctuation
      dynamics near equilibrium are studied via MD and associated time-dependent
      friction is analyzed via the generalized Langevin equation. Nonequilibrium
      solvent relaxation following an instantaneous change in the solute charge
      distribution and accompanying solvent structure reorganization are also
      investigated. Both equilibrium and nonequilibrium solvation dynamics are
      characterized by at least two vastly different time scales--a subpicosecond
      inertial regime followed by a slow diffusive regime. Solvent regions contributing
      to the subpicosecond nonequilibrium relaxation are found to vary significantly
      with initial solvation configurations, especially near the solute. If the solvent
      density near the solute is sufficiently high at the outset of the relaxation,
      subpicosecond dynamics are mainly governed by the motions of a few ions close to
      the solute. By contrast, in the case of a low local density, solvent ions located
      not only close to but also relatively far from the solute participate in the
      subpicosecond relaxation. Despite this difference, linear response holds
      reasonably well in both ionic liquids.

PMID- 15740272
TI  - Heteronuclear dipolar recoupling in solid-state nuclear magnetic resonance by
      amplitude-, phase-, and frequency-modulated Lee-Goldburg cross-polarization.
AB  - This paper presents a theoretical, numerical, and experimental study of phase-
      and frequency-switched Lee-Goldburg cross-polarization (FSLG-CP) under magic
      angle spinning conditions. It is shown that a well-defined amplitude modulation
      of one of the two radio-frequency (rf) fields in the FSLG-CP sequence results in
      highly efficient heteronuclear dipolar recoupling. The recoupled dipolar
      interaction is gamma-encoded and, under ideal conditions, the effective spin
      Hamiltonian is equivalent to that in continuous-wave Lee-Goldburg CP. In
      practice, however, FSLG-CP is less susceptible to rf field mismatch and
      inhomogeneity, and provides better suppression of (1)H spin diffusion. The
      performance of FSLG-CP is experimentally demonstrated on liquid-crystalline
      samples exhibiting motionally averaged dipolar couplings.

PMID- 15740273
TI  - Collision statistics, thermodynamics, and transport coefficients of hard
      hyperspheres in three, four, and five dimensions.
AB  - The collision statistics of hard hyperspheres are investigated. An exact,
      analytical formula is developed for the distribution of speeds of a sphere on
      collision, which is shown to be related to the average time between collisions
      for a sphere with a particular velocity. In addition, the relationship between
      the collision rate and the compressibility factor is generalized to arbitrary
      dimensions. Molecular dynamics simulations are performed for d=3, 4, and 5
      dimensional hard-hypersphere fluids. From these simulations, the equation of
      state of these systems, the self-diffusion coefficient, the shear viscosity, and
      the thermal conductivity are determined as a function of density. Various aspects
      of the collision statistics and their dependence on the density and
      dimensionality of the system are also studied.

PMID- 15740274
TI  - Ultrafast molecular dynamics of liquid aromatic molecules and the mixtures with
      CCl4.
AB  - The ultrafast molecular dynamics of liquid aromatic molecules, benzene, toluene,
      ethylbenzene, cumene, and 1,3-diphenylpropane, and the mixtures with CCl(4) have
      been investigated by means of femtosecond optical heterodyne-detected Raman
      induced Kerr effect spectroscopy. The picosecond Kerr transients of benzene,
      toluene, ethylbenzene, and cumene and the mixtures with CCl(4) show a
      biexponential feature. 1,3-Diphenylpropane and the mixtures with CCl(4) show
      triexponential picosecond Kerr transients. The slow relaxation time constants of
      the aromatic molecules and the mixtures with CCl(4) are qualitatively described
      by the Stoke-Einstein-Debye hydrodynamic model. The ultrafast dynamics have been
      discussed based on the Kerr spectra in the frequency range of 0-800 cm(-1)
      obtained by the Fourier transform analysis of the Kerr transients. The line
      shapes of the low-frequency intermolecular spectra located at 0-180 cm(-1)
      frequency range have been analyzed by two Brownian oscillators ( approximately 11
      cm(-1) and approximately 45 cm(-1) peaks) and an antisymmetric Gaussian function
      ( approximately 65 cm(-1) peak). The spectrum shape of 1,3-diphenylpropane is
      quite different from the spectrum shapes of the other aromatic molecules for the
      low magnitude of the low-frequency mode of 1,3-diphenylpropane and/or an
      intramolecular vibration. Although the concentration dependences of the low- and
      intermediate-frequency intermolecular modes (Brownian oscillators) do not show a
      significant trend, the width of high-frequency intermolecular mode (antisymmetric
      Gaussian) becomes narrower with the higher CCl(4) concentration for all the
      aromatics mixtures with CCl(4). The result indicates that the inhomogeneity of
      the intermolecular vibrational mode in aromatics/CCl(4) mixtures is decreasing
      with the lower concentration of aromatics. The intramolecular vibrational modes
      of the aromatic molecules observed in the Kerr spectra are also shown with the
      calculation results based on the density functional theory.

PMID- 15740275
TI  - Mean-field cage theory for the freezing of hard-sphere fluids.
AB  - Using some observations and some mean-field approximations, we develop a mean
      field cage theory for the freezing of hard-sphere fluids with v(f) > or =a(d) and
      obtain the freezing densities as functions of the closest-packing densities and
      the spatial densities, which are in good agreement with the experimental and
      simulation results.

PMID- 15740276
TI  - Feedback loops for chaos in activator-inhibitor systems.
AB  - Previous investigations have revealed that special constellations of feedback
      loops in a network can give rise to saddle-node and Hopf bifurcations and can
      induce particular bifurcation diagrams including the occurrence of various
      codimension-two points. To elucidate the role of feedback loops in the generation
      of more complex dynamics, a minimal prototype for these networks will be taken as
      purely periodic starting model which will be extended by an additional species in
      different feedback loops. The dynamics of the resulting systems will be analyzed
      numerically for the occurrence of chaotic attractors. Especially, the
      consequences of codimension-two bifurcations and the role of homoclinic orbits in
      view of the emergence of Shil'nikov chaos will be discussed.

PMID- 15740277
TI  - Six-dimensional quantum dynamics of dissociative chemisorption of H2 on Ru(0001).
AB  - Six-dimensional quantum dynamics calculations on dissociative chemisorption of
      H(2) on Ru(0001) are performed. The six-dimensional potential energy surface is
      generated using density functional theory. Two different generalized gradient
      approximations are used, i.e., RPBE and PW91, to allow the results to be
      compared. The dissociation probability for normally incident H(2) on a clean
      Ru(0001) surface is calculated. Large differences between the reaction
      probabilities calculated using the RPBE and PW91 are seen, with the PW91 results
      showing a much narrower reaction probability curve and a much higher reactivity.
      Using the reaction probabilities and assuming normal energy scaling reaction
      rates are generated for temperatures between 300 and 800 K. The rate generated
      using the PW91 results is higher by about a factor 5 than the rate based on the
      RPBE results in the range of temperatures relevant to ammonia production.

PMID- 15740278
TI  - Brownian dynamics simulation study of self-assembly of amphiphiles with large
      hydrophilic heads.
AB  - We have studied the effect of shape of an amphiphilic molecule on micellization
      properties by carrying out stochastic molecular dynamics simulation on a bead
      spring model of amphiphiles for several sizes of hydrophilic head group with a
      fixed hydrophobic tail length. Our studies show that the effect of geometry of an
      amphiphile on shape and cluster distribution of micelles is significant. We find
      the critical micelle concentration increases with the increasing size of the
      hydrophilic head. We demonstrate that the onset of micellization is accompanied
      by (i) a peak in the specific heat as found earlier in the simulation studies of
      lattice models, and (ii) a peak in the characteristic relaxation time of the
      cluster autocorrelation function. Amphiphiles with larger hydrophilic head form
      smaller micelles with sharper cluster distribution. Our studies are relevant to
      the controlled synthesis of nanostructures of desired shapes and sizes using self
      assembling properties of amphiphiles.

PMID- 15740279
TI  - Intermolecular effect in molecular electronics.
AB  - We investigate the effects of lateral interactions on the conductance of two
      molecules connected in parallel to semi-infinite leads. The method we use
      combines a Green function approach to quantum transport with density functional
      theory for the electronic properties. The system, modeled after a self-assembled
      monolayer, consists of benzylmercaptane molecules sandwiched between gold
      electrodes. We find that the conductance increases when intermolecular
      interaction comes into play. The source of this increase is the indirect
      interaction through the gold substrate rather than direct molecule-molecule
      interaction. A striking resonance is produced only 0.3 eV above the Fermi energy.

PMID- 15740280
TI  - Effect of the Ar-Ni(s) potential on the cross section for Ar+CH4/Ni{111}
      collision-induced desorption and the need for a more accurate CH4/Ni{111}
      potential.
AB  - In a previous paper [L. Sun, P. de Sainte Claire, O. Meroueh, and W. L Hase, J.
      Chem. Phys. 114, 535 (2001)], a classical trajectory simulation was reported of
      CH(4) desorption from Ni{111} by Ar-atom collisions. At an incident angle
      theta(i) of 60 degrees (with respect to the surface normal), the calculated
      collision-induced desorption (CID) cross sections are in excellent agreement with
      experiment. However, for smaller incident angles the calculated cross sections
      are larger than the experimental values and for normal collisions, theta(i)=0
      degrees , the calculated cross sections are approximately a factor of 2 larger.
      This trajectory study used an analytic function for the Ar+Ni(s) intermolecular
      potential which gives an Ar-Ni{111} potential energy minimum which is an order of
      magnitude too deep. In the work reported here, the previous trajectory study is
      repeated with an Ar+Ni(s) analytic intermolecular potential which gives an
      accurate Ar-Ni{111} potential energy minimum and also has a different surface
      corrugation than the previous potential. Though there are significant differences
      between the two Ar+Ni(s) analytic potentials, they have no important effects on
      the CID dynamics and the cross sections reported here are nearly identical to the
      previous values. Zero-point energy motions of the surface and the CH(4)-Ni(s)
      intermolecular modes are considered in the simulation and they are found to have
      a negligible effect on the CID cross sections. Calculations of the intermolecular
      potential between CH(4) and a Ni atom, at various levels of theory, suggest that
      there are substantial approximations in the ab initio calculation used to develop
      the CH(4)+Ni{111} potential. The implication is that the differences between the
      trajectory and experimental CID cross sections may arise from an inaccurate
      CH(4)+Ni{111} potential used in the trajectory simulation.

PMID- 15740281
TI  - Adsorption dynamics of CO2 on Zn-ZnO(0001): a molecular beam study.
AB  - Presented are initial S(0) and coverage Theta dependent, S(Theta), adsorption
      probability measurements, respectively, of CO(2) adsorption on the polar Zn
      terminated surface of ZnO, parametric in the impact energy E(i), the surface
      temperature T(s), the impact angle alpha(i), varied along the [001] azimuth, the
      CO(2) flux, and the density of defects, chi(Ar(+)), as varied by rare gas ion
      sputtering. S(0) decreases linearly from 0.72 to 0.25 within E(i)=0.12-1.33 eV
      and is independent of T(s). Above E(i)=0.56 eV, S(0) decreases by approximately
      0.2 with increasing alpha(i). The shape of S(Theta) curves is consistent with
      precursor-mediated adsorption (Kisliuk shape, i.e., S approximately const) for
      low E(i); above E(i)=0.56 eV, however, a turnover to adsorbate-assisted
      adsorption (S increases with Theta) has been observed. The initial slope of
      S(Theta) curves decreases thereby with increasing alpha(i), chi(Ar(+)), and T(s),
      i.e., the adsorbate-assisted adsorption is most distinct for normal impact on the
      pristine surface at low T(s) and is independent of the CO(2) flux. The S(Theta)
      curves have been parametrized by analytic precursor models and Monte Carlo
      simulations have been conducted as well. The temperature dependence of the
      saturation coverage shows two structures which could be assigned to adsorption on
      pristine and intrinsic defect sites, respectively, in agreement with a prior
      thermal desorption spectroscopy study. The heat of adsorption E(d) for the
      pristine sites amounts to 34.0-5.4Theta, whereas for adsorption on the intrinsic
      defect sites E(d) of approximately 43.6 kJ/mol could be estimated. Thus, a
      kinetic structure-activity relationship was present.

PMID- 15740282
TI  - A surface x-ray study of the structure and morphology of the oxidized Pd001
      surface.
AB  - The oxidation of Pd(100) and the formation of PdO was studied in situ using
      surface x-ray diffraction. A bulklike, epitaxial PdO film is formed at oxygen
      partial pressures beyond 1 mbar and sample temperatures exceeding 650 K. The main
      orientation is PdO(001)/Pd(001), based upon bulk reflections from the PdO film.
      By comparing with measurements from the Pd crystal truncation rods, we estimate
      an rms surface roughness of 6 A, in good agreement with previous high pressure
      scanning tunneling microscopy measurements. Finally, we observed the
      transformation from the (radical5 x radical5) surface oxide to PdO bulk oxide at
      675 K and 50 mbar O(2) pressure.

PMID- 15740283
TI  - Characterization of methoxy adsorption on some transition metals: a first
      principles density functional theory study.
AB  - Based on the gradient-density functional theory, calculation results of methoxy
      adsorption on Au(111), Ag(111), Cu(111), Pt(111), Pd(111), Ni(111), Rh(111), and
      Fe(100) surfaces are presented, and a consistent picture for some key physical
      properties determining the reactivity of metals appears. These eight metals
      belong to two groups: either with filled d electrons (group IB) or with unfilled
      but more than half filled d electrons (group VIII). The calculated adsorption
      energies are quite in agreement with the experimental data as well as the
      previous theoretical calculation results. Importantly, using the analysis of B.
      Hammer and J. K. Norskov, Nature (London) 376, 232 (1995) and in Chemisorption
      and Reactivity on Supported Clusters and Thin Films, edited by R. M. Lambert and
      G. Pacchioni (Kluwer Academic, Dordrecht, 1997), pp. 285-351, the binding
      energies have selectively been linearly correlated to the d-band center and to
      the size of the metal d-band orbital overlapping with the adsorbate (coupling
      matrix element) for these two groups of metals. And by analyzing the nature of
      the adsorption bonding, the possible reason of this difference is suggested.

PMID- 15740284
TI  - Efficient silicon surface and cluster modeling using quantum capping potentials.
AB  - A one-electron, silicon quantum capping potential for use in capping the dangling
      bonds formed by artificially limiting silicon clusters or surfaces is developed.
      The quantum capping potentials are general and can be used directly in any
      computational package that can handle effective core potentials. For silicon
      clusters and silicon surface models, we compared the results of traditional
      hydrogen atom capping with those obtained from capping with quantum capping
      potentials. The results clearly show that cluster and surface models capped with
      quantum capping potentials have ionization potentials, electron affinities, and
      highest occupied molecular orbital-lowest unoccupied molecular orbital gaps that
      are in very good agreement with those of larger systems. The silicon quantum
      capping potentials should be applied in cases where one wishes to model processes
      involving charges or low-energy excitations in silicon clusters and surfaces
      consisting of more than ca. 150 atoms.

PMID- 15740285
TI  - Exciton dynamics of GaSe nanoparticle aggregates.
AB  - Time-resolved and static spectroscopic results on GaSe nanoparticle aggregates
      are presented to elucidate the exciton relaxation and diffusion dynamics. These
      results are obtained in room-temperature TOP/TOPO solutions at various
      concentrations. The aggregate absorption spectra are interpreted in terms of
      electrostatic coupling and covalent interactions between particles. The spectra
      at various concentrations may then be interpreted in terms of aggregate
      distributions calculated from a simple equilibrium model. These distributions are
      used to interpret concentration-dependent emission anisotropy kinetics and time
      dependent emission spectral shifts. The emission spectra are reconstructed from
      the static emission spectra and decay kinetics obtained at a range of
      wavelengths. The results indicate that the aggregate z axis persistence length is
      about 9 particles. The results also show that the one-dimensional exciton
      diffusion coefficient is excitation wavelength dependent and has a value of about
      2 x 10(-5) cm(2)/s following 406 nm excitation. Although exciton diffusion
      results in very little energy relaxation, subsequent hopping of trapped
      electron/hole pairs occurs by a Forster mechanism and strongly red shifts the
      emission spectrum.

PMID- 15740286
TI  - Symmetry, delocalization, and molecular conductance.
AB  - Molecules bonded between two metal contacts form the simplest possible molecular
      devices. Coupled by the molecule, the left and right contact-based states form
      symmetric and antisymmetric pairs near the Fermi level. We relate the size of the
      resulting energy splitting DeltaE to the symmetry and degree of delocalization of
      the coupling molecular orbital. Qualitative trends in molecular conductances are
      then estimated from the variations in DeltaE. We examine benzenedithiol and other
      molecules of interest in transport.

PMID- 15740287
TI  - The proper structure of cubic ice confined in mesopores.
AB  - To examine the reason for the formation and the structure of cubic ice in a
      restricted space, we measured the powder x-ray diffraction patterns of cubic ice
      formed within the mesopores of porous silicas as a function of pore size (4-70
      nm). The results strongly suggest that cubic ice formed in the mesopores does not
      take a cubic structure as envisaged by Konig. It may be actually composed of very
      small crystallites of hexagonal ice that contains a large amount of growth faults
      depending on the crystallite size, that is, ice with disordered stacking
      sequence. Suppression of crystal growth of ice in the mesopores seems to be a
      vital factor for the formation and the stability of cubic ice.

PMID- 15740288
TI  - Density-functional study of oxygen adsorption on Mo(112).
AB  - Atomic oxygen adsorption on the Mo(112) surface has been investigated by means of
      first-principles total energy calculations. Among the variety of possible
      adsorption sites it was found that the bridge sites between two Mo atoms of the
      topmost row are favored for O adsorption at low and medium coverages. At about
      one monolayer coverage oxygen atoms prefer to adsorb in a quasithreefold hollow
      sites coordinated by two first-layer Mo atoms and one second layer atom. The
      stability of a structural model for an oxygen-induced p(2 x 3) reconstruction of
      the missing-row type is examined.

PMID- 15740289
TI  - Reflection absorption infrared spectroscopy and temperature programmed desorption
      investigations of the interaction of methanol with a graphite surface.
AB  - Reflection absorption infrared spectroscopy (RAIRS) and temperature programmed
      desorption (TPD) have been used to investigate the adsorption of methanol
      (CH(3)OH) on the highly oriented pyrolytic graphite (HOPG) surface. RAIRS shows
      that CH(3)OH is physisorbed at all exposures and that crystalline CH(3)OH can be
      formed, provided that the surface temperature and coverage are high enough. It is
      not possible to distinguish CH(3)OH that is closely associated with the HOPG
      surface from CH(3)OH adsorbed in multilayers using RAIRS. In contrast, TPD data
      show three peaks for the desorption of CH(3)OH. Initial adsorption leads to the
      observation of a peak assigned to the desorption of a monolayer. Subsequent
      adsorption leads to the formation of multilayers on the surface and two TPD peaks
      are observed which can be assigned to the desorption of multilayer CH(3)OH. The
      first of these shows a fractional order desorption, assigned to the presence of
      hydrogen bonding in the overlayer. The higher temperature multilayer desorption
      peak is only observed following very high exposures of CH(3)OH to the surface and
      can be assigned to the desorption of crystalline CH(3)OH.

PMID- 15740290
TI  - A diffusion model for the fluids confined in micropores.
AB  - The self-diffusion coefficients were calculated by molecular dynamics simulations
      and the effects of pore width, temperature, and fluid density on diffusion
      behavior of simple fluid argon and polar fluid water confined in micropores were
      analyzed and studied. A mathematical model describing diffusion behavior of
      fluids confined in micropores was proposed from the theories of molecular
      dynamics and molecular kinematics, and validated on the basis of the simulation
      results at various conditions. The model indicates that the diffusion coefficient
      is proportional to the square root of the pore width and to the temperature
      divided by the density squared. It is applicable to either liquid or gas states
      and only two parameters are required.

PMID- 15740291
TI  - Oxygen island formation on Pt(111) studied by dynamic Monte Carlo simulation.
AB  - The formation of oxygen islands on the Pt(111) surface has been studied as a
      function of temperature by low energy electron diffraction (LEED) experiments and
      dynamic Monte Carlo (DMC) simulations. By raising the temperature, the (2 x 2)
      LEED spot intensity increases gradually and decays after a peak at around 255 K
      (T(p)) with full width of half maximum of 160 K. This behavior is interpreted by
      DMC simulations with the kinematical LEED analysis. In the DMC simulation, an
      oxygen atom hops to the neighboring site via the activation barrier of the saddle
      point. The potential energies at initial, saddle, and final points are changed at
      each hopping event depending on the surrounding oxygen atoms. By comparing the
      observed T(p) with the simulated one, the interaction energy E of oxygen atoms on
      Pt(111) was determined to be 25+/-3 meV at 2a(0). The DMC simulations visualize
      how the oxygen islands are formed and collapse on Pt(111) with increase of the
      temperature and well reproduce the surface configurations observed by scanning
      tunneling microscopy.

PMID- 15740292
TI  - Pore formation in fluctuating membranes.
AB  - We study the nucleation of a single pore in a fluctuating lipid membrane,
      specifically taking into account the membrane fluctuations, as well as the shape
      fluctuations of the pore. For large enough pores, the nucleation free energy is
      well-described by shifts in the effective membrane surface tension and the pore
      line tension. Using our framework, we derive the stability criteria for the
      various pore formation regimes. In addition to the well-known large-tension
      regime from the classical nucleation theory of pores, we also find a low-tension
      regime in which the effective line and surface tensions can change sign from
      their bare values. The latter scenario takes place at sufficiently high
      temperatures, where the opening of a stable pore of finite size is entropically
      favorable.

PMID- 15740293
TI  - Rings-on-a-string chain structure in DNA.
AB  - Using fluorescence microscopy (FM), which permits the observation of single
      molecules, we found that a pearling structure is generated on a single long DNA
      molecule upon the addition of a gemini (dimeric) surfactant. This pearling
      structure was further investigated by performing atomic force microscopy
      measurements on the same DNA molecules as observed by FM. These observations
      revealed that the pearling structure is composed of many rings that are
      interconnected by elongated coil parts along a single DNA molecule, i.e., rings
      on-a-string structure. The mechanism of the formation of such an intrachain
      segregated structure in terms of microphase separation on a single
      polyelectrolyte chain is discussed.

PMID- 15740294
TI  - Electrostatic correlations and fluctuations for ion binding to a finite length
      polyelectrolyte.
AB  - A statistical mechanical model is presented which explicitly accounts for the
      fluctuations, the electrostatic, and the excluded volume correlations for ions
      bound to a polyelectrolyte such as DNA. The method can be employed to treat a
      wide range of ionic conditions including multivalent ions. The microscopic
      framework of the theory permits the use of realistic finite length and grooved
      structural model for the polyelectrolyte and modeling of the finite size of the
      bound ions. Test against Monte Carlo simulations suggests that the theory can
      give accurate predictions for the ion distribution and the thermodynamic
      properties. For multivalent ions, the theory makes improved predictions as
      compared with the mean-field approach. Moreover, for long polyelectrolyte and
      dilute salt concentration, the theory predicts ion binding properties that agree
      with the counterion condensation theory.

PMID- 15740296
TI  - Diffusion of spheres in crowded suspensions of rods.
AB  - Translational tracer diffusion of spherical macromolecules in crowded suspensions
      of rodlike colloids is investigated. Experiments are done using several kinds of
      spherical tracers in fd-virus suspensions. A wide range of size ratios L/2a of
      the length L of the rods and the diameter 2a of the tracer sphere is covered by
      combining several experimental methods: fluorescence correlation spectroscopy for
      small tracer spheres, dynamic light scattering for intermediate sized spheres,
      and video microscopy for large spheres. Fluorescence correlation spectroscopy is
      shown to measure long-time diffusion only for relatively small tracer spheres.
      Scaling of diffusion coefficients with a/xi, predicted for static networks, is
      not found for our dynamical network of rods (with xi the mesh size of the
      network). Self-diffusion of tracer spheres in the dynamical network of freely
      suspended rods is thus fundamentally different as compared to cross-linked
      networks. A theory is developed for the rod-concentration dependence of the
      translational diffusion coefficient at low rod concentrations for freely
      suspended rods. The proposed theory is based on a variational solution of the
      appropriate Smoluchowski equation without hydrodynamic interactions. The theory
      can, in principle, be further developed to describe diffusion through dynamical
      networks at higher rod concentrations with the inclusion of hydrodynamic
      interactions. Quantitative agreement with the experiments is found for large
      tracer spheres, and qualitative agreement for smaller spheres. This is probably
      due to the increasing importance of hydrodynamic interactions as compared to
      direct interactions as the size of the tracer sphere decreases.

PMID- 15740295
TI  - Phase separation of saturated and mono-unsaturated lipids as determined from a
      microscopic model.
AB  - A molecular model is proposed of a bilayer consisting of fully saturated
      dipalmitoylphosphatidylcholine (DPPC) and mono-unsaturated
      dioleoylphosphatidylcholine (DOPC). The model not only encompasses the constant
      density within the hydrophobic core of the bilayer, but also the tendency of
      chain segments to align. It is solved within self-consistent field theory. A
      model bilayer of DPPC undergoes a main-chain transition to a gel phase, while a
      bilayer of DOPC does not do so above zero degrees centigrade because of the
      double bond which disrupts order. We examine structural and thermodynamic
      properties of these membranes and find our results in reasonable accord with
      experiment. In particular, order-parameter profiles are in good agreement with
      NMR experiments. A phase diagram is obtained for mixtures of these lipids in a
      membrane at zero tension. The system undergoes phase separation below the main
      chain transition temperature of the saturated lipid. Extensions to the ternary
      DPPC, DOPC, and cholesterol system are outlined.

PMID- 15740297
TI  - Static and dynamic structures of spherical nonionic surfactant micelles during
      the disorder-order transition.
AB  - We have investigated the static and dynamic structures of nonionic surfactant
      micelles, a C(12)E(8)/water binary system, during the disorder-order transition
      using small angle x-ray scattering, static light scattering, and dynamic light
      scattering techniques. In the disordered phase, the micelles have spherical shape
      and intermicellar interactions are governed by the hard core and weak long ranged
      attractive potentials. With increase of the micellar concentration, the
      disordered micelles transform to the three characteristic ordered micellar
      phases, a hexagonally close packed lattice, a body centered cubic lattice, and an
      A15 lattice having area-minimizing structure. The stability of these phases is
      well explained by balance of a close packing rule and a minimal-area rule
      proposed by Ziherl and Kamien [Phys. Rev. Lett. 85, 3528 (2000)]. The role of
      hydrodynamic interactions in surfactant micellar solutions was compared with that
      in hard sphere colloidal particle suspensions.

PMID- 15740298
TI  - Coarse-grained computations for a micellar system.
AB  - We establish, through coarse-grained computation, a connection between
      traditional, continuum numerical algorithms (initial value problems as well as
      fixed point algorithms), and atomistic simulations of the Larson model of micelle
      formation. The procedure hinges on the (expected) evolution of a few slow, coarse
      grained mesoscopic observables of the Monte Carlo simulation, and on
      (computational) time scale separation between these and the remaining "slaved,"
      fast variables. Short bursts of appropriately initialized atomistic simulation
      are used to estimate the (coarse grained, deterministic) local dynamics of the
      evolution of the observables. These estimates are then in turn used to accelerate
      the evolution to computational stationarity through traditional continuum
      algorithms (forward Euler integration, Newton-Raphson fixed point computation).
      This "equation-free" framework, bypassing the derivation of explicit, closed
      equations for the observables (e.g., equations of state), may provide a
      computational bridge between direct atomistic/stochastic simulation and the
      analysis of its macroscopic, system-level consequences.

PMID- 15740299
TI  - Coarse-grained kinetic computations for rare events: application to micelle
      formation.
AB  - We discuss a coarse-grained approach to the computation of rare events in the
      context of grand canonical Monte Carlo (GCMC) simulations of self-assembly of
      surfactant molecules into micelles. The basic assumption is that the
      computational system dynamics can be decomposed into two parts-fast (noise) and
      slow (reaction coordinates) dynamics, so that the system can be described by an
      effective, coarse-grained Fokker-Planck (FP) equation. While such an assumption
      may be valid in many circumstances, an explicit form of FP equation is not always
      available. In our computations we bypass the analytic derivation of such an
      effective FP equation. The effective free energy gradient and the state-dependent
      magnitude of the random noise, which are necessary to formulate the effective
      Fokker-Planck equation, are obtained from ensembles of short bursts of
      microscopic simulations with judiciously chosen initial conditions. The reaction
      coordinate in our micelle formation problem is taken to be the size of a cluster
      of surfactant molecules. We test the validity of the effective FP description in
      this system and reconstruct a coarse-grained free energy surface in good
      agreement with full-scale GCMC simulations. We also show that, for very small
      clusters, the cluster size ceases to be a good reaction coordinate for a one
      dimensional effective description. We discuss possible ways to improve the
      current model and to take higher-dimensional coarse-grained dynamics into
      account.

PMID- 15740300
TI  - Further application of the constrained fluid lambda-integration method.
AB  - Previously we proposed a three stage, and recently a single stage nonphysical
      lambda-integration path for thermodynamically coupling bulk solid and liquid
      states directly. In this work we further apply these paths, specifically the
      newer single stage path, to the calculation of the complete truncated and shifted
      Lennard-Jones (R(cutoff)=2.5sigma) and aluminum glue potential melting lines, and
      the zero pressure melting point for a commonly used gold glue potential. The
      results showed accurate agreement with presently available literature. We found
      the single stage constrained fluid lambda-integration methodology to be robust in
      terms of reversibility over this extended range of temperatures, pressures, and
      intermolecular potentials.

PMID- 15740303
TI  - Chemisorption sites of CO on small gold clusters and transitions from
      chemisorption to physisorption.
AB  - Gold clusters adsorbed with CO, Au(m)(CO)(n) (-) (m=2-5; n=0-7), were studied by
      photoelectron spectroscopy (PES). The first few CO adsorptions were observed to
      induce significant redshifts to the PES spectra relative to pure gold clusters.
      For each Au cluster, a critical CO number (n(c)) was observed, beyond which the
      PES spectra of Au(m)(CO)(n) (-) change very little with increasing n. n(c) was
      shown to correspond exactly to the available low coordination apex sites in each
      Au cluster. CO first chemisorbs to these sites and additional CO then only
      physisorbs to the chemisorption-sautrated Au(m)(CO)(n) (-) complexes.

PMID- 15740304
TI  - Gaussian split Ewald: A fast Ewald mesh method for molecular simulation.
AB  - Gaussian split Ewald (GSE) is a versatile Ewald mesh method that is fast and
      accurate when used with both real-space and k-space Poisson solvers. While real
      space methods are known to be asymptotically superior to k-space methods in terms
      of both computational cost and parallelization efficiency, k-space methods such
      as smooth particle-mesh Ewald (SPME) have thus far remained dominant because they
      have been more efficient than existing real-space methods for simulations of
      typical systems in the size range of current practical interest. Real-space GSE,
      however, is approximately a factor of 2 faster than previously described real
      space Ewald methods for the level of force accuracy typically required in
      biomolecular simulations, and is competitive with leading k-space methods even
      for systems of moderate size. Alternatively, GSE may be combined with a k-space
      Poisson solver, providing a conveniently tunable k-space method that performs
      comparably to SPME. The GSE method follows naturally from a uniform framework
      that we introduce to concisely describe the differences between existing Ewald
      mesh methods.

PMID- 15740305
TI  - van der Waals interactions of polycyclic aromatic hydrocarbon dimers.
AB  - Density functional theory is in principle exact and includes also long-range
      interactions, such as the van der Waals interactions. These are, however, part of
      the exchange-correlation energy functional that needs to be approximated, and are
      absent in the local and semilocal standard implementations. Recently a density
      functional which includes van der Waals interactions for planar systems has been
      developed, which we show can be extended to provide a treatment of planar
      molecules. We use this functional to calculate binding distances and energies for
      dimers of three of the smallest polycyclic aromatic hydrocarbons (PAHs)-
      naphthalene, anthracene, and pyrene.

PMID- 15740306
TI  - Accurate hybrid stochastic simulation of a system of coupled chemical or
      biochemical reactions.
AB  - The dynamical solution of a well-mixed, nonlinear stochastic chemical kinetic
      system, described by the Master equation, may be exactly computed using the
      stochastic simulation algorithm. However, because the computational cost scales
      with the number of reaction occurrences, systems with one or more "fast"
      reactions become costly to simulate. This paper describes a hybrid stochastic
      method that partitions the system into subsets of fast and slow reactions,
      approximates the fast reactions as a continuous Markov process, using a chemical
      Langevin equation, and accurately describes the slow dynamics using the integral
      form of the "Next Reaction" variant of the stochastic simulation algorithm. The
      key innovation of this method is its mechanism of efficiently monitoring the
      occurrences of slow, discrete events while simultaneously simulating the dynamics
      of a continuous, stochastic or deterministic process. In addition, by introducing
      an approximation in which multiple slow reactions may occur within a time step of
      the numerical integration of the chemical Langevin equation, the hybrid
      stochastic method performs much faster with only a marginal decrease in accuracy.
      Multiple examples, including a biological pulse generator and a large-scale
      system benchmark, are simulated using the exact and proposed hybrid methods as
      well as, for comparison, a previous hybrid stochastic method. Probability
      distributions of the solutions are compared and the weak errors of the first two
      moments are computed. In general, these hybrid methods may be applied to the
      simulation of the dynamics of a system described by stochastic differential,
      ordinary differential, and Master equations.

PMID- 15740307
TI  - The E x e dynamic Jahn-Teller problem: a new insight from the strong coupling
      limit.
AB  - Correct boundary conditions for the E x e dynamic Jahn-Teller problem are
      considered explicitly for the first time to obtain approximate analytical
      solutions in the strong coupling limit. Numerical solutions for the decoupled
      equations using the finite difference method are also presented. The numerical
      solutions for the decoupled equations exhibit avoided crossings in the weak
      coupling region, which explains the oscillating behavior of the solutions
      obtained by Longuet-Higgins et al. for the coupled equations. The obtained
      analytical energy expressions show improved agreement with the numerical
      calculations as compared with the previous treatment in which the potentials were
      assumed to be harmonic. We demonstrate that the pseudorotational energy
      j(2)/(2g(2)), where g is the dimensionless vibronic coupling constant, and j
      total angular momentum: j=+/-1/2,+/-3/2,..., in the conventional strong coupling
      expression for the vibronic levels of the lower sheet is exact. Non-Hermitian
      first-order perturbation theory gives the energy which is correct up to 1/g(4).
      The asymptotic behavior of the wave function at the origin does not influence the
      corrected energy up to order of 1/g(4). At the same time the treatment of the
      upper sheet with correct boundary conditions gives solutions which are entirely
      different from the corresponding Slonczewski's solutions. Besides, the correct
      boundary conditions enable us to evaluate the nonadiabatic coupling between the
      lower and upper potential sheets. The energy correction due to the nonadiabatic
      coupling is estimated to be of order 1/g(6).

PMID- 15740308
TI  - Fast centroid molecular dynamics: a force-matching approach for the
      predetermination of the effective centroid forces.
AB  - A fast centroid molecular dynamics (CMD) methodology is proposed in which the
      effective centroid forces are predetermined through a force-matching algorithm
      applied to a standard path integral molecular dynamics simulation. The resulting
      method greatly reduces the computational cost of generating centroid
      trajectories, thus extending the applicability of CMD. The method is applied to
      the study of liquid para-hydrogen at two state points and liquid ortho-deuterium
      at one state point. The static and dynamical results are compared to those
      obtained from full adiabatic CMD simulations and found to be in excellent
      agreement for all three systems; the transport properties are also compared to
      experiment and found to have a similar level of agreement.

PMID- 15740309
TI  - Finite bias conductance of an Anderson level: a source--Liouville Hartree-Fock
      study.
AB  - We address the problem of stationary conductance through an Anderson spin
      degenerate level at finite bias. Just as in the Anderson solution, for a finite
      bias in parameter space (bias, gate voltage, interaction constant, and the
      couplings to the leads) there exist spin-polarized and non-spin-polarized
      regions. The transition curve between them is found analytically for the case of
      symmetric coupling to the left and right leads. We approach the problem by a non
      Markovian source-Liouville equation where the two-body interaction self-energies
      are taken in the Hartree-Fock approximation.

PMID- 15740310
TI  - Cubic response functions in time-dependent density functional theory.
AB  - We present density-functional theory for time-dependent response functions up to
      and including cubic response. The working expressions are derived from an
      explicit exponential parametrization of the density operator and the Ehrenfest
      principle, alternatively, the quasienergy ansatz. While the theory retains the
      adiabatic approximation, implying that the time-dependency of the functional is
      obtained only implicitly-through the time dependence of the density itself rather
      than through the form of the exchange-correlation functionals-it generalizes
      previous time-dependent implementations in that arbitrary functionals can be
      chosen for the perturbed densities (energy derivatives or response functions). In
      particular, general density functionals beyond the local density approximation
      can be applied, such as hybrid functionals with exchange correlation at the
      generalized-gradient approximation level and fractional exact Hartree-Fock
      exchange. With our implementation the response of the density can always be
      obtained using the stated density functional, or optionally different functionals
      can be applied for the unperturbed and perturbed densities, even different
      functionals for different response order. As illustration we explore the use of
      various combinations of functionals for applications of nonlinear optical
      hyperpolarizabilities of a few centrosymmetric systems; molecular nitrogen,
      benzene, and the C(60) fullerene. Considering that vibrational, solvent, and
      local field factors effects are left out, we find in general that very good
      experimental agreement can be obtained for the second dynamic hyperpolarizability
      of these systems. It is shown that a treatment of the response of the density
      beyond the local density approximation gives a significant effect. The use of
      different functional combinations are motivated and discussed, and it is
      concluded that the choice of higher order kernels can be of similar importance as
      the choice of the potential which governs the Kohn-Sham orbitals.

PMID- 15740311
TI  - Multiconfiguration self-consistent-field theory based upon the fragment molecular
      orbital method.
AB  - The fragment molecular orbital (FMO) method was combined with the
      multiconfiguration self-consistent-field (MCSCF) theory. One- and two-layer
      approaches were developed, the former involving all dimer MCSCF calculations and
      the latter limiting MCSCF calculations to a small part of the system. The
      accuracy of the two methods was tested using the six electrons in six orbitals
      complete active space type of MCSCF and singlet spin state for phenol+(H(2)O)(n),
      n=16,32,64 (6-31G( *) and 6-311G( *) basis sets); alpha helices and beta strands
      of phenylalanine-(alanine)(n), n=4,8,16 (6-31G( *)). Both double-zeta and triple
      zeta quality basis sets with polarization were found to have very similar
      accuracy. The error in the correlation energy was at most 0.000 88 a.u., the
      error in the gradient of the correlation energy was at most 6.x10(-5) a.u./bohr
      and the error in the correlation correction to the dipole moment was at most
      0.018 D. In addition, vertical singlet-triplet electron excitation energies were
      computed for phenol+(H(2)O)(n), (n=16,32,64), 6-31G( *), and the errors were
      found to be at most 0.02 eV. Approximately linear scaling was observed for the
      FMO-based MCSCF methods. As an example, an FMO-based MCSCF calculation with 1262
      basis functions took 98 min on one 3.0 GHz Pentium4 node with 1 Gbyte RAM.

PMID- 15740312
TI  - Intramolecular energy transfer through charge transfer state in lanthanide
      compounds: a theoretical approach.
AB  - A theoretical approach for the intramolecular energy transfer process involving
      the ligand-to-metal charge transfer (LMCT) state in lanthanide compounds is
      developed. Considering a two-electron interaction, both the direct Coulomb and
      exchange interactions are taken into account, leading to expressions from which
      selection rules may be derived and transfer rates may be calculated. These
      selection rules show that the direct Coulomb and exchange mechanisms are
      complementary, in the same way as obtained in previous works for the case of
      ligand-lanthanide ion energy transfer processes. An important result from
      numerical estimates is that the channel ligand-LMCT state is by far the dominant
      case, leading to transfer rates higher than for the channel lanthanide ion-LMCT
      state by several orders of magnitude. The analysis of the emission quantum yield
      as a function of the relative energy position of the LMCT state in a typical
      Eu(3+) compound allows the identification of two quenching regions, the most
      pronounced one occurring close to the lower ligand triplet level.

PMID- 15740313
TI  - Coupled cluster methods including triple excitations for excited states of
      radicals.
AB  - We report an extension of the coupled cluster iterative-triples model, CC3, to
      excited states of open-shell molecules, including radicals. We define the method
      for both spin-unrestricted Hartree-Fock (UHF) and spin-restricted open-shell
      Hartree-Fock (ROHF) reference determinants and discuss its efficient
      implementation in the PSI3 program package. The program is streamlined to use at
      most O(N(7)) computational steps and avoids storage of the triple-excitation
      amplitudes for both the ground- and excited-state calculations. The excitation
      energy program makes use of a Lowdin projection formalism (comparable to that of
      earlier implementations) that allows computational reduction of the Davidson
      algorithm to only the single- and double-excitation space, but limits the
      calculation to only one excited state at a time. However, a root-following
      algorithm may be used to compute energies for multiple states of the same
      symmetry. Benchmark applications of the new methods to the lowest valence (2)B(1)
      state of the allyl radical, low-lying states of the CH and CO(+) diatomics, and
      the nitromethyl radical show substantial improvement over ROHF- and UHF-based
      CCSD excitation energies for states with strong double-excitation character or
      cases suffering from significant spin contamination. For the allyl radical, CC3
      adiabatic excitation energies differ from experiment by less than 0.02 eV, while
      for the (2)Sigma(+) state of CH, significant errors of more than 0.4 eV remain.

PMID- 15740314
TI  - Propagator corrections to adiabatic time-dependent density-functional theory
      linear response theory.
AB  - It has long been known that only one-electron excitations are available from
      adiabatic time-dependent density functional theory (TDDFT). This is particularly
      clear in Casida's formulation of TDDFT linear response theory. Nevertheless the
      explicit inclusion of two- and higher-electron excitations is necessary for an
      adequate description of some excited states, notably the first excited singlet
      states of butadiene and quartet excited states of molecules with a doublet ground
      state. The equation-of-motion superoperator approach is used here to derive a
      Casida-like propagator equation which can be clearly separated into an adiabatic
      part and a nonadiabatic part. The adiabatic part is identified as corresponding
      to Casida's equation for adiabatic TDDFT linear response theory. This equivalence
      is confirmed by deriving a general formula which includes the result that Gonze
      and Scheffler derived to show the equivalence of TDDFT and Gorling-Levy adiabatic
      connection perturbation theory for the exchange-only optimized effective
      potential. The nonadiabatic part explicitly corrects adiabatic TDDFT for two- and
      higher-electron excitations. The "dressed TDDFT" of Maitra, Zhang, Cave, and
      Burke is obtained as a special case where the ground state is closed shell. The
      extension of dressed TDDFT to the case where the ground state is an open-shell
      doublet is presented, highlighting the importance of correctly accounting for
      symmetry in this theory. The extension to other ground state spin symmetries is a
      straightforward consequence of the present work.

PMID- 15740315
TI  - Targeted Car-Parrinello molecular dynamics: elucidating double proton transfer in
      formic acid dimer.
AB  - The targeted molecular dynamics method, making possible the study of rare events,
      has been assessed in the framework of Car-Parrinello ab initio molecular
      dynamics. As a test case, we have studied the staggered-eclipsed rotation of
      ethane. The technique has subsequently been applied to investigate the nature of
      double proton transfer in formic acid dimer. The latter is found to follow a
      concerted transfer mechanism involving an essentially planar transition state. A
      "funnel-like region" of the potential energy surface is identified, where floppy
      intermolecular modes stiffen upon approaching the transition state.

PMID- 15740316
TI  - An investigation of valence shell orbital momentum profiles of difluoromethane by
      binary (e,2e) spectroscopy.
AB  - The electron binding energy spectra and momentum profiles of the valence orbitals
      of difluoromethane, also known as HFC32 (HFC-hydrofluorocarbon) (CH(2)F(2)), have
      been studied by using a high resolution (e,2e) electron momentum spectrometer, at
      an impact energy of 1200 eV plus the binding energy, and by using symmetric
      noncoplanar kinematics. The experimental momentum profiles of the outer valence
      orbitals and 4a(1) inner valence orbital are compared with the theoretical
      momentum distributions calculated using Hartree-Fock and density functional
      theory (DFT) methods with various basis sets. In general, the shapes of the
      experimental momentum distributions are well described by both the Hartree-Fock
      and DFT calculations when large and diffuse basis sets are used. However, the
      result also shows that it is hard to choose the different calculations for some
      orbitals, including the methods and the size of the basis sets employed. The pole
      strength of the ionization peak from the 4a(1) inner valence orbital is
      estimated.

PMID- 15740317
TI  - Multireference configuration interaction calculations for positronium halides.
AB  - Multireference configuration interaction (MRCI) calculations of the positronium
      halides, PsF, PsCl, PsBr, and PsI, are carried out, to give positron ionization
      energies, positronium binding energies, and two-photon annihilation rates. All CI
      calculations consider only valence correlation effect with a frozen-core
      approximation, and use the orbitals with angular momentum up to 8. To incorporate
      the effects of many-body correlations in the energies and two-photon annihilation
      rates, the MRCI calculations are repeated with increasing reference
      configurations, and the full CI limits of these energies and annihilation rates
      are estimated. The contribution from orbitals having angular momentum greater
      than 8 to those values is also estimated. Relative to our previous single
      reference CI calculations, many-body correlation effects significantly increase
      the positron ionization energies, positronium binding energies, and two-photon
      annihilation rates. The structures of the positronium halides are also discussed.

PMID- 15740318
TI  - Theoretical investigation of the SO(2+) dication and the photo-double ionization
      spectrum of SO.
AB  - Highly correlated ab initio methods were used in order to generate the potential
      energy curves of the electronic states of the SO(2+) dication and of the
      electronic ground state of the neutral SO molecule. These curves were used to
      predict the spectroscopic properties of this dication and to perform forward
      calculations of the double photoionization spectrum of SO. In light of spin-orbit
      calculations, the metastability of this doubly charged ion is discussed: for
      instance, the rovibrational levels of the X (1)Sigma(+) and A (3)Sigma(+) states
      are found to present relatively long lifetimes. In contrast, the other electronic
      excited states should predissociate to form S(+) and O(+) in their electronic
      ground states. The simulated spectrum shows structures due to transitions between
      the v=0 vibrational level of SO (X (3)Sigma(-)) and the vibrational levels below
      the barrier maximum of 11 of the calculated electronic states. The 2 (1)Sigma(+)
      electronic state of SO(2+) received further treatment: in addition to vibrational
      bands due to the below barrier energy levels of this electronic state, at least
      nine continuum resonances were predicted which are responsible for the special
      shape of the spectrum in this energy region. This work is predictive in nature
      and should stimulate future experimental investigations dealing with this
      dication.

PMID- 15740319
TI  - Time-dependent quantum mechanical wave packet study of the He+H(2) (+)(v,j)-
      >HeH(+)+H reaction.
AB  - A detailed three-dimensional time-dependent quantum dynamical study of the
      He+H(2) (+)(v=0-3,j=0)-->HeH(+)+H reaction is reported for different vibrational
      v states of H(2) (+) in its ground rotational (j=0) state over a range of
      translational E(trans) energies on an accurate ab initio potential energy surface
      published by Palmieri et al. Plots of reaction probability as a function of total
      energy E reveal a large number of oscillations indicating the presence of a
      number of reactive scattering resonances. When averaged over total angular
      momentum J, some of the oscillations survive, indicating that they may be
      amenable to experimental observation. A comparison of our present results with
      our earlier results on the McLaughlin-Thompson-Joseph-Sathyamurthy surface and
      the experimental results from different research groups reveal a good deal of
      agreement as well as some discrepancies between theory and experiment at the
      level of state-selected gas phase dynamics.

PMID- 15740320
TI  - Ab initio potential energy surfaces, total absorption cross sections, and product
      quantum state distributions for the low-lying electronic states of N(2)O.
AB  - Adiabatic potential energy surfaces for the six lowest singlet electronic states
      of N(2)O (X (1)A('), 2 (1)A('), 3 (1)A('), 1 (1)A("), 2 (1)A(") and 3 (1)A("))
      have been computed using an ab initio multireference configuration interaction
      (MRCI) method and a large orbital basis set (aug-cc-pVQZ). The potential energy
      surfaces display several symmetry related and some nonsymmetry related conical
      intersections. Total photodissociation cross sections and product rotational
      state distributions have been calculated for the first ultraviolet absorption
      band of the system using the adiabatic ab initio potential energy and transition
      dipole moment surfaces corresponding to the lowest three excited electronic
      states. In the Franck-Condon region the potential energy curves corresponding to
      these three states lie very close in energy and they all contribute to the
      absorption cross section in the first ultraviolet band. The total angular
      momentum is treated correctly in both the initial and final states. The total
      photodissociation spectra and product rotational distributions are determined for
      N(2)O initially in its ground vibrational state (0,0,0) and in the vibrationally
      excited (0,1,0) (bending) state. The resulting total absorption spectra are in
      good quantitative agreement with the experimental results over the region of the
      first ultraviolet absorption band, from 150 to 220 nm. All of the lowest three
      electronically excited states [(1)Sigma(-)(1 (1)A(")), (1)Delta(2 (1)A(')), and
      (1)Delta(2 (1)A("))] have zero transition dipole moments from the ground state
      [(1)Sigma(+)(1 (1)A('))] in its equilibrium linear configuration. The absorption
      becomes possible only through the bending motion of the molecule. The (1)Delta(2
      (1)A('))<--X (1)Sigma(+)((1)A(')) absorption dominates the absorption cross
      section with absorption to the other two electronic states contributing to the
      shape and diffuse structure of the band. It is suggested that absorption to the
      bound (1)Delta(2 (1)A(")) state makes an important contribution to the
      experimentally observed diffuse structure in the first ultraviolet absorption
      band. The predicted product rotational quantum state distribution at 203 nm
      agrees well with experimental observations.

PMID- 15740321
TI  - New CO-CO interaction potential tested by rovibrational calculations.
AB  - A four-dimensional potential energy surface (PES) for the CO dimer consisting of
      rigid molecules has been calculated, using a scheme that combines density
      functional theory to describe the monomers and symmetry adapted perturbation
      theory for the interaction energy (DFT-SAPT). The potential is fitted in terms of
      analytic functions, and the fitted potential is used to compute the lowest
      rovibrational states of the dimer. The quality of the PES is comparable to that
      of a previously published surface, which was calculated with the coupled cluster
      single double and perturbative triples [CCSD(T)] method. It is shown that a
      weighted average of the DFT-SAPT and the CCSD(T) potential gives results that are
      in very good agreement with experimental data, for both ((12)CO)(2) and
      ((13)CO)(2). The relative weight was determined by adjusting the energy gap
      between the origins of the lowest two stacks of rotational levels of ((12)CO)(2)
      to the measured value.

PMID- 15740322
TI  - Photodissociation dynamics of IBr(-)(CO(2))(n), n<15.
AB  - We report the ionic photoproducts produced following photoexcitation of mass
      selected IBr(-)(CO(2))(n), n=0-14, cluster ions at 790 and 355 nm. These
      wavelengths provide single state excitation to two dissociative states,
      corresponding to the A(') (2)Pi(1/2) and B 2 (2)Sigma(1/2) (+) states of the IBr(
      ) chromophore. Excitation of these states in IBr(-) leads to production of I(
      )+Br and Br(-)+I( *), respectively. Potential energy curves for the six lowest
      electronic states of IBr(-) are calculated, together with structures for IBr(
      )(CO(2))(n), n=1-14. Translational energy release measurements on
      photodissociated IBr(-) determine the I-Br(-) bond strength to be 1.10+/-0.04 eV;
      related measurements characterize the A(') (2)Pi(1/2)<--X (2)Sigma(1/2) (+)
      absorption band. Photodissociation product distributions are measured as a
      function of cluster size following excitation to the A(') (2)Pi(1/2) and B 2
      (2)Sigma(1/2) (+) states. The solvent is shown to drive processes such as spin
      orbit relaxation, charge transfer, recombination, and vibrational relaxation on
      the ground electronic state. Following excitation to the A(') (2)Pi(1/2)
      electronic state, IBr(-)(CO(2))(n) exhibits size-dependent cage fractions
      remarkably similar to those observed for I(2) (-)(CO(2))(n). In contrast,
      excitation to the B 2 (2)Sigma(1/2) (+) state shows extensive trapping in excited
      states that dominates the recombination behavior for all cluster sizes we
      investigated. Finally, a pump-probe experiment on IBr(-)(CO(2))(8) determines the
      time required for recombination on the ground state following excitation to the
      A(') state. While the photofragmentation experiments establish 100% recombination
      in the ground electronic state for this and larger IBr(-) cluster ions, the time
      required for recombination is found to be approximately 5 ns, some three orders
      of magnitude longer than observed for the analogous I(2) (-) cluster ion.
      Comparisons are made with similar experiments carried out on I(2) (-)(CO(2))(n)
      and ICl(-)(CO(2))(n) cluster ions.

PMID- 15740323
TI  - Photoelectron anisotropy and channel branching ratios in the detachment of
      solvated iodide cluster anions.
AB  - Photoelectron spectra and angular distributions in 267 nm detachment of the I(
      )Ar, I(-)H(2)O, I(-)CH(3)I, and I(-)CH(3)CN cluster anions are examined in
      comparison with bare I(-) using velocity-map photoelectron imaging. In all cases,
      features are observed that correlate to two channels producing either
      I((2)P(3/2)) or I((2)P(1/2)). In the photodetachment of I(-) and I(-)Ar, the
      branching ratios of the (2)P(1/2) and (2)P(3/2) channels are observed to be
      approximately 0.4, in both cases falling short of the statistical ratio of 0.5.
      For I(-)H(2)O and I(-)CH(3)I, the (2)P(1/2) to (2)P(3/2) branching ratios are
      greater by a factor of 1.6 compared to the bare iodide case. The relative
      enhancement of the (2)P(1/2) channel is attributed to dipole effects on the final
      state continuum wave function in the presence of polar solvents. For I(-)CH(3)CN
      the (2)P(1/2) to (2)P(3/2) ratio falls again, most likely due to the proximity of
      the detachment threshold in the excited spin-orbit channel. The photoelectron
      angular distributions in the photodetachment of I(-), I(-)Ar, I(-)H(2)O, and I(
      )CH(3)CN are understood within the framework of direct detachment from I(-).
      Hence, the corresponding anisotropy parameters are modeled using variants of the
      Cooper-Zare central-potential model for atomic-anion photodetachment. In
      contrast, I(-)CH(3)I yields nearly isotropic photoelectron angular distributions
      in both detachment channels. The implications of this anomalous behavior are
      discussed with reference to alternative mechanisms, affording the solvent
      molecule an active role in the electron ejection process.

PMID- 15740324
TI  - Molecules in high spin states III: the millimeter/submillimeter-wave spectrum of
      the MnCl radical (X (7)Sigma(+)).
AB  - The pure rotational spectrum of the MnCl radical (X (7)Sigma(+)) has been
      recorded in the range 141-535 GHz using millimeter-submillimeter direct
      absorption spectroscopy. This work is the first time the molecule has been
      studied with rotational resolution in its ground electronic state. MnCl was
      synthesized by the reaction of manganese vapor, produced in a Broida-type oven,
      with Cl(2). Transitions of both chlorine isotopomers were measured, as well as
      lines originating in several vibrationally excited states. The presence of
      several spin components and manganese hyperfine interactions resulted in quite
      complex spectra, consisting of multiple blended features. Because 42 rotational
      transitions were measured for Mn(35)Cl over a wide range of frequencies with high
      signal-to-noise, a very accurate set of rotational, fine structure, and hyperfine
      constants could be determined with the aid of spectral simulations. Spectroscopic
      constants were also determined for Mn(37)Cl and several vibrationally excited
      states. The values of the spin-rotation and spin-spin parameters were found to be
      relatively small (gamma=11.2658 MHz and lambda=1113.10 MHz for Mn(35)Cl); in the
      case of lambda, excited electronic states contributing to the second-order spin
      orbit interaction may be canceling each other. The Fermi contact hyperfine term
      was found to be large in manganese chloride with b(F)(Mn(35)Cl)=397.71 MHz, a
      result of the manganese 4s character mixing into the 12sigma orbital. This
      orbital is spsigma hybridized, and contains some Mn 4psigma character, as well.
      Hence, it also contributes to the dipolar constant c, which is small and positive
      for this radical (c=32.35 MHz for Mn(35)Cl). The hyperfine parameters in MnCl are
      similar to those of MnH and MnF, suggesting that the bonding in these three
      molecules is comparable.

PMID- 15740325
TI  - Femtosecond dynamics of Cu(H(2)O)(2).
AB  - The ultrafast relaxation dynamics of Cu(H(2)O)(2) is investigated using
      femtosecond photodetachment-photoionization spectroscopy. In addition, stationary
      points on the Cu(H(2)O)(2) anion, neutral, and cation potential energy surfaces
      are characterized by ab initio electronic structure calculations. Electron
      photodetachment from Cu(-)(H(2)O)(2) initiates the dynamics on the ground-state
      potential energy surface of neutral Cu(H(2)O)(2). The resulting Cu(H(2)O)(2)
      complexes experience large-amplitude H(2)O reorientation and dissociation. The
      time evolution of the Cu(H(2)O)(2) fragmentation products is monitored by time
      resolved resonant multiphoton ionization. The parent ion, Cu(+)(H(2)O)(2), is not
      detected above background levels. The rise to a maximum of the Cu(+) signal from
      Cu(-)(H(2)O)(2), and the decay of the Cu(+)(H(2)O) signal from Cu(-)(H(2)O)(2)
      have similar tau approximately 10 ps time dependences to the corresponding
      signals from Cu(-)(H(2)O), but display clear differences at very short and long
      times. The experimental observations can be understood in terms of the following
      picture. Prompt dissociation of H(2)O from nascent Cu(H(2)O)(2) gives rise to a
      vibrationally excited Cu(H(2)O) complex, which dissociates to Cu+H(2)O due to
      coupling of H(2)O internal rotation to the dissociation coordinate. This prompt
      dissociation removes all intra-H(2)O vibrational excitation from the intermediate
      Cu(H(2)O) fragment, which quenches the long time vibrational predissociation to
      Cu+H(2)O previously observed in analogous experiments on Cu(-)(H(2)O).

PMID- 15740326
TI  - Electronic effect on protonated hydrogen-bonded imidazole trimer and
      corresponding derivatives cationized by alkali metals (Li(+), Na(+), and K(+)).
AB  - The electronic effects on the protonated hydrogen-bonded imidazole trimer
      (Im)(3)H(+) and the derivatives cationized by alkali metals (Li(+), Na(+), and
      K(+)) are investigated using B3LYP method in conjunction with the 6-311+G( *)
      basis set. The prominent characteristics of (Im)(3)H(+) on reduction are the
      backflow of the transferred proton to its original fragment and the remoteness of
      the H atom from the attached side bare N atom. The proton transfer occurs on both
      reduction and oxidation for the corresponding hydrogen-bonded imidazole trimer.
      For the derivatives cationized by Li(+), (Im)(3)Li(+), the backflow of the
      transferred proton occurs on reduction. The electron detachment from respective
      highest occupied molecular orbital of (Im)(3)Na(+) and (Im)(3)K(+) causes the
      proton transferring from the fragment attached by the alkali metal cation to the
      middle one. The order of the adiabatic ionization potentials of (Im)(3)M(+) is
      (Im)(3)H(+)>(Im)(3)Li(+)>(Im)(3)Na(+)>(Im)(3)K(+); the order of (Im)(3)M
      indicates that (Im)(3)H is the easicst complex to be ionized. The polarity of
      (Im)(3)M(+) (M denotes H, Li, Na, and K) increases on both oxidation and
      reduction. The (Im)(3)M(+) complexes dissociate into (Im)(3) and M(+) except
      (Im)(3)H(+), which dissociates preferably into (Im)(3) (+) and H atom, while the
      neutral complexes [(Im)(3)M] dissociate into (Im)(3) and M. The stabilization
      energy of (Im)(3)Li(2+), (Im)(3)Na(2+), and (Im)(3)K(2+) indicate that their
      energies are higher as compared to those of the monomers.

PMID- 15740327
TI  - First principles study of the diatomic charged fluorides MF(+/-), M=Sc, Ti, V,
      Cr, and Mn.
AB  - Employing multireference configuration interaction and coupled-cluster methods in
      conjunction with quantitative basis sets, we have explored the electronic
      structure of the charged diatomic fluorides MF(+/-), where M=Sc, Ti, V, Cr, and
      Mn. In addition, and in order to complete our recently published work on the
      neutral diatomic fluorides MF, M=Ti-Mn, we have also examined the ground (X
      (1)Sigma(+)) and the first excited state (alpha (3)Delta) of neutral ScF. For the
      entire anionic MF(-) series and the cations ScF(+), VF(+), and MnF(+), no
      experimental or theoretical results of any kind have been reported so far in the
      literature. For the charged MF(+/-) sequence we have investigated a total of
      43=29(MF(+))+14(MF(-)) states, reporting potential energy curves, energetics, and
      common spectroscopic parameters. Two are the most interesting conclusions of the
      present work. (a) The Coulombic binding character of MF(+) cations, i.e., the
      conformity of their equilibrium description to M(2+)F(-) and (b) the atypical
      bonding of the MF(-) anions and their surprisingly high dissociation energies (up
      to 85 kcal/mol for the X (2)Delta state of ScF(-)). Considering the complexities
      of these chemically "simple" systems, our results on ScF, TiF(+), and CrF(+) are
      in very good agreement with the limited experimental findings.

PMID- 15740328
TI  - Photoelectron spectroscopy and ab initio study of the doubly antiaromatic B(6) (2
      ) dianion in the LiB(6) (-) cluster.
AB  - A metal-boron mixed cluster LiB(6) (-) was produced and characterized by
      photoelectron spectroscopy and ab initio calculations. A number of electronic
      transitions were observed and used to compare with theoretical calculations. An
      extensive search for the global minimum of LiB(6) (-) was carried out via an ab
      initio genetic algorithm technique. The pyramidal C(2v) ((1)A(1)) molecule was
      found to be the most stable at all levels of theory. The nearest low-lying isomer
      was found to be a triplet C(2) ((3)B) structure, 9.2 kcal/mol higher in energy.
      Comparison of calculated detachment transitions from LiB(6) (-) and the
      experimental photoelectron spectra confirmed the C(2v) pyramidal global minimum
      structure. Natural population calculation revealed that LiB(6) (-) is a charge
      transfer complex, Li(+)B(6) (2-), in which Li(+) and B(6) (2-) interact in a
      primarily ionic manner. Analyses of the molecular orbitals and chemical bonding
      of B(6) (2-) showed that the planar cluster is twofold (pi- and sigma-)
      antiaromatic, which can be viewed as the fusion of two aromatic B(3) (-) units.

PMID- 15740329
TI  - Time-resolved intraband electronic relaxation dynamics of Hg(n) (-) clusters (n=7
      13,15,18) excited at 1.0 eV.
AB  - Time-resolved photoelectron imaging has been used to study the relaxation
      dynamics of small Hg(n) (-) clusters (n=7-13,15,18) following intraband
      electronic excitation at 1250 nm (1.0 eV). This study furthers our previous
      investigation of single electron, intraband relaxation dynamics in Hg(n) (-)
      clusters at 790 nm by exploring the dynamics of smaller clusters (n=7-10), as
      well as those of larger clusters (n=11-13,15,18) at a lower excitation energy. We
      measure relaxation time scales of 2-9 ps, two to three times faster than seen
      previously after 790 nm excitation of Hg(n) (-), n=11-18. These results, along
      with size-dependent trends in the absorption cross-section and photoelectron
      angular distribution anisotropy, suggest significant evolution of the cluster
      anion electronic structure in the size range studied here. Furthermore, the
      smallest clusters studied here exhibit 35-45 cm(-1) oscillations in pump-probe
      signal at earliest temporal delays that are interpreted as early coherent nuclear
      motion on the excited potential energy surfaces of these clusters. Evidence for
      evaporation of one or two Hg atoms is seen on a time scale of tens of
      picoseconds.

PMID- 15740330
TI  - An ab initio study of the structure, torsional potential energy function, and
      electric properties of disilane, ethane, and their deuterated isotopomers.
AB  - Highly accurate ab initio computations of the molecular structure and properties,
      torsional potential energy function, and harmonic force field of disilane and
      ethane have been carried out. Equilibrium parameters as well as vibrational
      corrections have been evaluated. In addition, for these systems a vibrational
      averaging procedure has been employed for calculating the dipole moment of
      molecules which have no permanent dipole moment, i.e., SiH(3)SiD(3) and
      CH(3)CD(3). The molecular and spectroscopic properties calculated for ethane and
      its isotopomers provide a calibration against known experimental data, allowing
      us to estimate the reliability of our computed results for disilane for which
      there is much less experimental data. The goal of the present study is to predict
      the molecular parameters, with estimated uncertainties, that determine the
      microwave spectrum of SiH(3)SiD(3).

PMID- 15740331
TI  - A (2)A(2)<--X (2)B(1) absorption and Raman spectra of the OClO molecule: a three
      dimensional time-dependent wave packet study.
AB  - Time-dependent wave packet calculations of the (A (2)A(2)<--X (2)B(1)) absorption
      and Raman spectra of the OClO molecule are reported. The Fourier grid Hamiltonian
      method in three dimensions is employed. The X (2)B(1) ground state ab initio
      potential energy surface reported by Peterson is used together with his
      corresponding A (2)A(2) state surface or the revised surface of the A (2)A(2)
      state by Xie and Guo. Radau coordinates are used to describe the vibrations of a
      nonrotating OClO molecule. The split-operator method combined with fast Fourier
      transform is applied to propagate the wave function. We find that the ab initio A
      (2)A(2) potential energy surface better reproduces the detailed structures of the
      absorption spectrum at long wavelength, while the revised surface of the A
      (2)A(2) state, consistent with the work of Xie and Guo, better reproduces the
      overall shape and the energies of the vibrational levels. Both surfaces of the A
      (2)A(2) state can reasonably reproduce the experimental Raman spectra but neither
      does so in detail for the numerical model employed in the present work.

PMID- 15740332
TI  - Secondary structures of short peptide chains in the gas phase: double resonance
      spectroscopy of protected dipeptides.
AB  - The conformational structure of short peptide chains in the gas phase is studied
      by laser spectroscopy of a series of protected dipeptides, Ac-Xxx-Phe-NH(2),
      Xxx=Gly, Ala, and Val. The combination of laser desorption with supersonic
      expansion enables us to vaporize the peptide molecules and cool them internally;
      IR/UV double resonance spectroscopy in comparison to density functional theory
      calculations on Ac-Gly-Phe-NH(2) permits us to identify and characterize the
      conformers populated in the supersonic expansion. Two main conformations,
      corresponding to secondary structures of proteins, are found to compete in the
      present experiments. One is composed of a doubly gamma-fold corresponding to the
      2(7) ribbon structure. Topologically, this motif is very close to a beta-strand
      backbone conformation. The second conformation observed is the beta-turn,
      responsible for the chain reversal in proteins. It is characterized by a
      relatively weak hydrogen bond linking remote NH and CO groups of the molecule and
      leading to a ten-membered ring. The present gas phase experiment illustrates the
      intrinsic folding properties of the peptide chain and the robustness of the beta
      turn structure, even in the absence of a solvent. The beta-turn population is
      found to vary significantly with the residues within the sequence; the Ac-Val-Phe
      NH(2) peptide, with its two bulky side chains, exhibits the largest beta-turn
      population. This suggests that the intrinsic stabilities of the 2(7) ribbon and
      the beta-turn are very similar and that weakly polar interactions occurring
      between side chains can be a decisive factor capable of controlling the secondary
      structure.

PMID- 15740333
TI  - Breakdown of the mirror image symmetry in the optical absorption/emission spectra
      of oligo(para-phenylene)s.
AB  - The absorption and emission spectra of most luminescent, pi-conjugated, organic
      molecules are the mirror image of each other. In some cases, however, this
      symmetry is severely broken. In the present work, the asymmetry between the
      absorption and fluorescence spectra in molecular systems consisting of para
      linked phenyl rings is studied. The vibronic structure of the emission and
      absorption bands is calculated from ab initio quantum chemical methods and a
      subsequent, rigorous Franck-Condon treatment. Good agreement with experiment is
      achieved. A clear relation can be established between the strongly anharmonic
      double-well potential for the phenylene ring librations around the long molecular
      axis and the observed deviation from the mirror image symmetry. Consequences for
      related compounds and temperature dependent optical measurements are also
      discussed.

PMID- 15740334
TI  - Thermal decomposition of RDX from reactive molecular dynamics.
AB  - We use the recently developed reactive force field ReaxFF with molecular dynamics
      to study thermal induced chemistry in RDX [cyclic-[CH(2)N(NO(2))](3)] at various
      temperatures and densities. We find that the time evolution of the potential
      energy can be described reasonably well with a single exponential function from
      which we obtain an overall characteristic time of decomposition that increases
      with decreasing density and shows an Arrhenius temperature dependence. These
      characteristic timescales are in reasonable quantitative agreement with
      experimental measurements in a similar energetic material, HMX [cyclic
      [CH(2)N(NO(2))](4)]. Our simulations show that the equilibrium population of CO
      and CO(2) (as well as their time evolution) depend strongly of density: at low
      density almost all carbon atoms form CO molecules; as the density increases
      larger aggregates of carbon appear leading to a C deficient gas phase and the
      appearance of CO(2) molecules. The equilibrium populations of N(2) and H(2)O are
      more insensitive with respect to density and form in the early stages of the
      decomposition process with similar timescales.

PMID- 15740335
TI  - The absorption and excitation spectroscopy of matrix-isolated atomic manganese:
      sites of isolation in the solid rare gases.
AB  - This study collects information from absorption and luminescence excitation
      spectra recorded for Mn atoms isolated in the solid rare gases Ar, Kr, and Xe and
      presents an analysis of the site occupancy, based on the polarizabilities of the
      rare gases and the observed spectral shifts. Two thermally stable sites of
      isolation exist for atomic Mn in solid Ar and Kr, while a single thermally stable
      site is present in Mn/Xe. Site occupancy assignments are based on the application
      of a polarizability model to the z (6)P(5/2)<--a (6)S(5/2); z (8)P(5/2)<--a
      (6)S(5/2), and y (6)P(5/2)<--a (6)S(5/2) electronic transitions of atomic Mn.
      From an analysis of the observed RG matrix-to-gas phase energy shifts for P<--S
      type transitions, this model allows the association of certain site types
      occupied by metal atoms in the rare gas solids. The required condition being a
      linear dependence of the matrix shifts with rare gas polarizability for those
      metal atoms "trapped" in a particular site type. Application of the
      polarizability model in conjunction with trends observed in site dominance,
      established a connection between the blue sites in Ar and Kr and the single site
      in Xe. Use of the known MgRG ground state bond lengths facilitated an
      identification of the sites of Mn atom isolation assuming the transference of the
      known MgRG bond lengths to the MnRG systems. Substitutional site occupancy of
      atomic Mn is assigned to the blue sites in Ar and Kr and the single site in Xe,
      while tetra-vacancy site occupancy is assigned to the red sites in Ar and Kr.
      Consistent with these assignments, Mn atoms in solid Ar show a preference for
      trapping in tetra-vacancy sites whereas in solid Kr, single substitutional sites
      are preferred and in Xe, this is the only site observed.

PMID- 15740336
TI  - Isomolar semigrand ensemble molecular dynamics: development and application to
      liquid-liquid equilibria.
AB  - An extended system molecular dynamics method for the isomolar semigrand ensemble
      (fixed number of particles, pressure, temperature, and fugacity fraction) is
      developed and applied to the calculation of liquid-liquid equilibria (LLE) for
      two Lennard-Jones mixtures. The method utilizes an extended system variable to
      dynamically control the fugacity fraction xi of the mixture by gradually
      transforming the identity of particles in the system. Two approaches are used to
      compute coexistence points. The first approach uses multiple-histogram
      reweighting techniques to determine the coexistence xi and compositions of each
      phase at temperatures near the upper critical solution temperature. The second
      approach, useful for cases in which there is no critical solution temperature, is
      based on principles of small system thermodynamics. In this case a coexistence
      point is found by running N-P-T-xi simulations at a common temperature and
      pressure and varying the fugacity fraction to map out the difference in chemical
      potential between the two species A and B (mu(A)-mu(B)) as a function of
      composition. Once this curve is known the equal-distance/equal-area criterion is
      used to determine the coexistence point. Both approaches give results that are
      comparable to those of previous Monte Carlo (MC) simulations. By formulating this
      approach in a molecular dynamics framework, it should be easier to compute the
      LLE of complex molecules whose intramolecular degrees of freedom are often
      difficult to properly sample with MC techniques.

PMID- 15740337
TI  - A study of the phase behavior of a simple model of chiral molecules and
      enantiomeric mixtures.
AB  - We present a study of the solid-fluid and solid-solid phase equilibrium for
      molecular models representative of chiral molecules and enantiomeric mixtures.
      The models consist of four hard sphere interaction sites of different diameters
      in a tetrahedral arrangement with the fifth hard sphere interaction site at the
      center of the tetrahedron. The volumetric properties and free energies of the
      pure enantiomers and binary mixtures were calculated in both fluid and solid
      phases using isobaric Monte Carlo simulations. The models exhibit essentially
      ideal solution behavior in the fluid phase with little chiral discrimination. In
      the solid phase the effects of chirality are much greater. Solid-fluid phase
      behavior involving the pure enantiomer solids and also racemic compounds was
      calculated. The calculations indicate that, depending on the relative sizes of
      the hard sphere interaction sites, packing effects alone can be sufficient to
      stabilize a racemic compound with respect to the pure enantiomer solids.

PMID- 15740338
TI  - Local hydrogen bonding dynamics and collective reorganization in water: ultrafast
      infrared spectroscopy of HOD/D(2)O.
AB  - We present an investigation into hydrogen bonding dynamics and kinetics in water
      using femtosecond infrared spectroscopy of the OH stretching vibration of HOD in
      D(2)O. Infrared vibrational echo peak shift and polarization-selective pump-probe
      experiments were performed with mid-IR pulses short enough to capture all
      relevant dynamical processes. The experiments are self-consistently analyzed with
      a nonlinear response function expressed in terms of three dynamical parameters
      for the OH stretching vibration: the frequency correlation function, the
      lifetime, and the second Legendre polynomial dipole reorientation correlation
      function. It also accounts for vibrational-relaxation-induced excitation of
      intermolecular motion that appears as heating. The long time, picosecond behavior
      is consistent with previous work, but new dynamics are revealed on the sub-200 fs
      time scale. The frequency correlation function is characterized by a 50 fs decay
      and 180 fs beat associated with underdamped intermolecular vibrations of hydrogen
      bonding partners prior to 1.4 ps exponential relaxation. The reorientational
      correlation function observes a 50 fs librational decay prior to 3 ps diffusive
      reorientation. Both of these correlation functions compare favorably with the
      predictions from classical molecular dynamics simulations. The time-dependent
      behavior can be separated into short and long time scales by the 340 fs
      correlation time for OH frequency shifts. The fast time scales arise from
      dynamics that are mainly local: fluctuations in hydrogen bond distances and
      angles within relatively fixed intermolecular configurations. On time scales
      longer than the correlation time, dephasing and reorientations reflect collective
      reorganization of the liquid structure. Since the OH transition frequency and
      dipole are only weakly sensitive to these collective coordinates, this is a
      kinetic regime which gives an effective rate for exchange of intermolecular
      structures.

PMID- 15740339
TI  - Time series analysis of ion dynamics in glassy ionic conductors obtained by a
      molecular dynamics simulation.
AB  - We present several characteristics of ionic motion in glassy ionic conductors
      brought out by time series analysis of molecular dynamics (MD) simulation data.
      Time series analysis of data obtained by MD simulation can provide crucial
      information to describe, understand and predict the dynamics in many systems. The
      data have been treated by the singular spectrum analysis (SSA), which is a method
      to extract information from noisy short time series and thus provide insight into
      the unknown or partially unknown dynamics of the underlying system that generated
      the time series. Phase-space plot reconstructed using the principal components of
      SSA exhibited complex but clear structures, suggesting the deterministic nature
      of the dynamics.

PMID- 15740340
TI  - Ab initio studies of a water layer at transition metal surfaces.
AB  - This paper presents a detailed study of a water adlayer adsorbed on Pt(111) and
      Rh(111) surfaces using periodic density functional theory methods. The
      interaction between the metal surface and the water molecules is assessed from
      molecular dynamics simulation data and single point electronic structure
      calculations of selected configurations. It is argued that the electron bands
      around the Fermi level of the metal substrate extend over the water adlayer. As a
      consequence in the presence of the water layer the surface as a whole still
      maintains its metallic conductivity-a result of a crucial importance for
      understanding the process of electron transfer through the water/metal interface
      and electrochemical reactions in particular. Our results also indicate that there
      exists a weak bond between the hydrogen of the water and the Rh metal atoms as
      opposed to the widespread (classical) models based on purely repulsive
      interaction. This suggests that the commonly used classical interactions
      potentials adopted for large scale molecular dynamics simulations of water/metal
      interfaces may need revision. Two adsorption models of water on transition metals
      with the OH bonds pointing towards or away of the surface are also examined. It
      is shown that due to the very close values of their adsorption energies one
      should consider the real structure of water on the surface as a mixture of these
      simple "up" and "down" models. A model for the structure of the adsorbed water
      layer on Rh(111) is proposed in terms of statistical averages from molecular
      dynamics simulations.

PMID- 15740341
TI  - Mechanisms of lithium transport in amorphous polyethylene oxide.
AB  - We report calculations using a previously reported model of lithium perchlorate
      in polyethylene oxide in order to understand the mechanism of lithium transport
      in these systems. Using an algorithm suggested by Voter, we find results for the
      diffusion rate which are quite close to experimental values. By analysis of the
      individual events in which large lithium motions occur during short times, we
      find that no single type of rearrangement of the lithium environment
      characterizes these events. We estimate the free energies of the lithium ion as a
      function of position during these events by calculation of potentials of mean
      force and thus derive an approximate map of the free energy as a function of
      lithium position during these events. The results are consistent with a Marcus
      like picture in which the system slowly climbs a free energy barrier dominated by
      rearrangement of the polymer around the lithium ions, after which the lithium
      moves very quickly to a new position. Reducing the torsion forces in the model
      causes the diffusion rates to increase.

PMID- 15740342
TI  - Thermally activated mechanisms of hydrogen abstraction by growth precursors
      during plasma deposition of silicon thin films.
AB  - Hydrogen abstraction by growth precursors is the dominant process responsible for
      reducing the hydrogen content of amorphous silicon thin films grown from SiH(4)
      discharges at low temperatures. Besides direct (Eley-Rideal) abstraction, gas
      phase radicals may first adsorb on the growth surface and abstract hydrogen in a
      subsequent process, giving rise to thermally activated precursor-mediated (PM)
      and Langmuir-Hinshelwood (LH) abstraction mechanisms. Using results of first
      principles density functional theory (DFT) calculations on the interaction of
      SiH(3) radicals with the hydrogen-terminated Si(001)-(2x1) surface, we show that
      precursor-mediated abstraction mechanisms can be described by a chemisorbed
      SiH(3) radical hopping between overcoordinated surface Si atoms while being
      weakly bonded to the surface before encountering a favorable site for hydrogen
      abstraction. The calculated energy barrier of 0.39 eV for the PM abstraction
      reaction is commensurate with the calculated barrier of 0.43-0.47 eV for
      diffusion of SiH(3) on the hydrogen-terminated Si(001)-(2x1) surface, which
      allows the radical to sample the entire surface for hydrogen atoms to abstract.
      In addition, using the same type of DFT analysis we have found that LH reaction
      pathways involve bond breaking between the silicon atoms of the chemisorbed
      SiH(3) radical and the film prior to hydrogen abstraction. The LH reaction
      pathways exhibit energy barriers of 0.76 eV or higher, confining the abstraction
      only to nearest-neighbor hydrogens. Furthermore, we have found that LH processes
      compete with radical desorption from the hydrogen-terminated Si(001)-(2x1)
      surface and may be suppressed by the dissociation of chemisorbed SiH(3) radicals
      into lower surface hydrides. Analysis of molecular-dynamics simulations of the
      growth process of plasma deposited silicon films have revealed that qualitatively
      similar pathways for thermally activated hydrogen abstraction also occur commonly
      on the amorphous silicon growth surface.

PMID- 15740343
TI  - Electronic properties of a pure and sodium-doped C(70) single layer adsorbed on
      Al polycrystalline surface.
AB  - Core level and valence band photoemission measurements combined with near edge x
      ray absorption fine structure measurements were performed on a single C(70) layer
      adsorbed on polycrystalline Al (1 ML-C(70)/Al) (ML-monolayer), pure and doped
      with sodium atoms. The data obtained from the pure ML chemisorbed on Al surface
      show a semiconducting behavior of the system, which is characterized by a
      covalent bond between the adsorbate and the substrate. The same data show also
      that the C(70) molecules tend to orient themselves with the C(5v) axis
      perpendicular to the surface in analogy to what observed for 1 ML-C(70)/Cu(111).
      By doping the sample with sodium atoms a charge transfer from the alkali atoms to
      the lowest unoccupied molecular orbital (LUMO) of the C(70) molecules takes
      place, as underlined by the gradual increasing intensity of the C(70) LUMO peak
      as a function of doping. Nevertheless, no metallic phases are observed for any
      doping step.

PMID- 15740344
TI  - Determining the geometry of strongly hydrogen-bonded silanols in a layered
      hydrous silicate by solid-state nuclear magnetic resonance.
AB  - High-resolution solid-state NMR spectroscopy is exploited to obtain structural
      constraints involving strongly hydrogen-bonded silanols in octosilicate, a
      prominent member of the layered hydrous sodium silicates. Proton-silicon cross
      polarization dynamics reveals that octosilicate contains two types of Q(3)
      silicons present in hydrogen-bonded -Si-O-Hcdots, three dots, centeredO-Si- and 
      Si-O(-)-type sites which can only be distinguished by their different abilities
      to cross polarize and the different mobilities of neighboring hydrous species.
      The theoretical analysis of the oscillating components of the polarization
      transfer buildup curves suggests that the model of heteronuclear pairs is an
      adequate description of the quantum spin system within hydrogen-bonded -Si-O
      Hcdots, three dots, centeredO-Si- fragments. We also show that dipolar modulated,
      slow speed magic-angle (29)Si NMR spectrum provides unique geometric information
      on strongly hydrogen-bonded silanols. The dipolar modulated spinning sidebands
      contain all the information necessary to determine the internuclear Sicdots,
      three dots, centeredH distances as well as the magnitude and orientation of the
      principal elements of the (29)Si chemical shielding tensor in the molecular
      frame. The data provide definite proof of the intralayer character of strongly
      hydrogen-bonded silanol groups in a bridging, albeit not symmetric, position
      between neighboring tetrahedra. The approach developed in this work may be useful
      to obtain structural information on related layered alkali metal silicates,
      silica gels as well as on other classes of microporous materials.

PMID- 15740345
TI  - Adsorption kinetics and patterning of a Si(111)-7 x 7 surface by dissociation of
      methanol.
AB  - CH(3)OH undergoes dissociation on a Si(111)-7 x 7 surface via a two dimensionally
      free precursor. The sticking probability attained by the STM (scanning tunneling
      microscopy) was entirely coverage independent, where the observed image
      represented the final state of the adsorption. CH(3)OH dissociates equally on the
      faulted and unfaulted halves at room temperature. However, the dissociation at
      the center adatom-rest atom site is four times preferential to that at the corner
      adatom-rest atom site in each half unit cell. Such site selectivity,
      center/corner, changes with the occupation of adatoms in corresponding half unit
      cell, that is, center/corner=4 for the half unit cell with one reacted adatom,
      but 2.6 and 1.8 for the half unit cells with two and three reacted adatoms,
      respectively. Such site selectivity is well rationalized by the dissociation
      depending on the local conformation of the site instead of the local density of
      states (LDOS). The site selectivity of center/corner is well reproduced by
      considering the occurrence probability of the whole dissociation pattern. As the
      STM image represents the final state of the adsorption, if the final step of
      adsorption involves dissociation of molecule or precursor, the STM image reflects
      the dissociation probability depending on the local structure. On the other hand,
      if no dissociation of molecule or precursor is involved at the final step, the
      adsorption probability might depend on the LDOS. The adsorption of H(2)S, H(2)O,
      and NH(3) is also discussed from this general viewpoint of adsorption. The
      concept of a two dimensionally free precursor will be important to understand the
      kinetics of heterogeneous catalysis.

PMID- 15740346
TI  - The birth of a bubble: a molecular simulation study.
AB  - We study the nucleation of a bubble in a metastable Lennard-Jones (LJ) fluid,
      confined to a spherical pore with wetting walls, by a combination of grand
      canonical, canonical ensemble, and gauge cell Monte Carlo simulation methods
      complemented by the Voronoi-Delaunay tessellation analysis of statistical
      geometry of intermolecular cavities. We construct the isotherm of confined fluid
      in the form of a continuous van der Waals' loop, in which the unstable backward
      trajectory between the spinodals corresponds to bubble states. We show that as
      the degree of metastability increases and the fluid becomes progressively
      stretched, the decrease of fluid density is associated with the evolution of a
      population of interstitial intermolecular cavities. At the spinodal, the fluid
      becomes mechanically unstable: Interstitial cavities partly coalesce into a
      larger cavity located due to the system symmetry around the pore center. This
      cavity represents a bubble embryo, which grows at the expense of interstitial
      cavities. The nucleation barrier is calculated by direct thermodynamic
      integration along the isotherm. We compare our simulation results to the
      predictions of the classical nucleation theory and experiments on capillary
      condensation-evaporation of nitrogen in pores of hybrid organic-inorganic
      mesoporous molecular sieve HMM-3.

PMID- 15740347
TI  - Observation of a deuteron nuclear magnetic resonance Knight shift in conductive
      polyaniline.
AB  - Solid state deuteron magic angle spinning nuclear magnetic resonance spectra of
      conductive ring-deuterated polyaniline consist of two peaks, one at the same
      chemical shift as the insulating form of the polymer and the second shifted by
      5.8+/-1 ppm. The magnitude of the shift is field and temperature independent and
      is identified as a Knight shift. The deuterons undergoing a Knight shift
      originate from both the crystalline and amorphous regions of the sample, implying
      that conduction is mediated by delocalized polarons in both these regions. Spin
      count experiments demonstrate that in highly conductive samples, signal is lost
      not only by dephasing due to the proximity of localized unpaired electrons but
      also to high rf reflectance.

PMID- 15740348
TI  - Heat flow in proteins: computation of thermal transport coefficients.
AB  - The rate of vibrational energy transfer and thermal transport coefficients are
      computed for two structurally distinct proteins, green fluorescent protein (GFP)
      and myoglobin. The computation of thermal transport coefficients exploits the
      scaling of the energy diffusion coefficient with the vibrational mode frequency
      of a protein. Near 300 K we find that vibrational energy transfer due to
      anharmonicity contributes substantially to thermal transport because of the
      localization of many thermally accessible normal modes. The thermal diffusivity
      for the beta-barrel GFP is larger than that for myoglobin, particularly at low
      temperature due to a mean free path for vibrational energy propagation that is
      twice as large at low frequency. Vibrational energy transfer is also faster in
      GFP than in myoglobin for most vibrational modes.

PMID- 15740349
TI  - Calculation of the entropy and free energy by the hypothetical scanning Monte
      Carlo method: application to peptides.
AB  - A new approach, the hypothetical scanning Monte Carlo (HSMC), for calculating the
      absolute entropy, S, and free energy, F, has been introduced recently and applied
      first to fluids (argon and water) and later to peptides. In this paper the method
      is further developed for peptide chains in vacuum. S is calculated from a given
      MC sample by reconstructing each sample conformation i step-by-step, i.e.,
      calculating transition probabilities (TPs) for the dihedral and bond angles and
      fixing the related atoms at their positions. At step k of the process the chain's
      coordinates that have already been determined are kept fixed (the "frozen past")
      and TP(k) is obtained from a MC simulation of the "future" part of the chain
      whose TPs as yet have not been determined; when the process is completed the
      contribution of conformation i to the entropy is, S(i) approximately -ln Pi(k)
      TP(k). In a recent paper we studied polyglycine chains, modeled by the AMBER
      force field with constant bond lengths and bond angles (the rigid model).
      Decaglycine [(Gly)(10)] was studied in the helical, extended, and hairpin
      microstates, while (Gly)(16) was treated only in the first two microstates. In
      this paper the samples are increased and restudied, (Gly)(16) is also
      investigated in the hairpin microstate, and for (Gly)(10) approximations are
      tested where only part of the future is considered for calculating the TPs. We
      calculate upper and lower bounds for F and demonstrate that like for fluids, F
      can be obtained from multiple reconstructions of a single conformation. We also
      test a more realistic model of (Gly)(10) where the bond angles are allowed to
      move (the flexible model). Very accurate results for S and F are obtained which
      are compared to results obtained by the quasiharmonic approximation and the local
      states method. Thus, differences in entropy and free energy between the three
      microstates are obtained within errors of 0.1-0.3 kcal/mol. The HSMC method can
      be applied to a macromolecule with any degree of flexibility, ranging from local
      fluctuations to a random coil. The present results demonstrate that the
      difference in stability, DeltaF(mn)=F(m)-F(n) between significantly different
      microstates m and n, can be obtained from two simulations only without the need
      to resort to thermodynamic integration. Our long-term goal is to extend this
      method to any peptide and apply it to a peptide immersed in a box with explicit
      water.

PMID- 15740350
TI  - Intramolecular fluorescence quenching in luminescent copolymers containing
      fluorenone and fluorene units: a direct measurement of intrachain exciton hopping
      rate.
AB  - The quenching process of fluorescence emission in polyfluorene (PF) due to the
      presence of intramolecular 9-fluorenone (9 FL) moieties is studied in dilute
      toluene solution as a function of 9 FL content in eight copolymers containing
      both fluorene and fluorenone units (PF/FL(x)). The absorption spectrum of
      PF/FL(x) copolymers clearly shows a new absorption band, redshifted relatively to
      the PF and 9-fluorenone absorption, which increases in intensity when the
      fluorenone fraction increases and also decreases with solvent polarity.
      Fluorescence emission spectra of PF/FL(x) show that this redshifted and
      unstructured emission does not coincide with the 9-fluorenone emission and, with
      increasing solvent polarity, it further redshifts and decreases in intensity. An
      isoemissive point is clearly observed on the fluorescence emission spectra of
      PF/FL(x) as a function of fluorenone content, showing that the new emission band
      is formed at the expense of PF. We propose the formation of an intramolecular
      charge transfer complex (ICTC) between PF units and 9-fluorenone to explain the
      appearance of the new emission band. Global analysis of time resolved
      fluorescence decays collected at 415 nm (PF emission) and 580 nm (the ICTC
      emission) show that three exponentials are generally needed to achieve excellent
      fits. Two of the components (420 ps and 6.5 ns) are independent of 9-fluorenone
      fraction. A further fast component is strongly dependent on fluorenone fraction
      and ranges between 280 and 70 ps. This component appears as a decay time at 415
      nm and as a rise time at 580 nm and is ascribed to the migration of exciton to
      quenching sites (formation of intramolecular CT complex or exciton ionization at
      CT complex). A kinetic mechanism involving three different kinetic species,
      quenched PF units kinetically coupled with the ICTC complex, and unquenched PF
      units is proposed to explain the experimental data and the quenching rate
      constant is obtained, k(1) congruent with 10(11) s(-1). This is an experimental
      measurement of the intrachain exciton hopping rate.

PMID- 15740352
TI  - Mechanical properties of the domains of titin in a Go-like model.
AB  - Comparison of properties of three domains of titin, I1, I27, and I28, in a simple
      geometry-based model shows that despite a high structural homology between their
      native states different domains show similar but distinguishable mechanical
      properties. Folding properties of the separate domains are predicted to be
      diversified which reflects sensitivity of the kinetics to the details of native
      structures. The Go-like model corresponding to the experimentally resolved native
      structure of the I1 domain is found to provide the biggest thermodynamic and
      mechanical stability compared to the other domains studied here. We analyze
      elastic, thermodynamic, and kinetic properties of several structures
      corresponding to the I28 domain as obtained through homology-based modeling. We
      discuss the ability of the models of the I28 domain to reproduce experimental
      results qualitatively. A strengthening of contacts that involve hydrophobic amino
      acids does not affect theoretical comparisons of the domains. Tandem linkages of
      up to five identical or different domains unravel in a serial fashion at low
      temperatures. We study the nature of the intermediate state that arises in the
      early stages of the serial unraveling and find it to qualitatively agree with the
      results of Marszalek et al.

PMID- 15740353
TI  - Coarse-grained description of polymer blends as interacting soft-colloidal
      particles.
AB  - We present a theoretical approach which maps polymer blends onto mixtures of soft
      colloidal particles. The analytical mesoscale pair correlation functions
      reproduce well data from united atom molecular dynamics simulations of polyolefin
      mixtures without fitting parameters. The theory exactly recovers the analytical
      expressions for density and concentration fluctuation structure factors of soft
      colloidal mixtures (liquid alloys).

PMID- 15740351
TI  - Charge induced pattern formation on surfaces: segregation in cylindrical micelles
      of cationic-anionic peptide-amphiphiles.
AB  - Micelles, vesicles, and films composed of two species of incompatible
      heterogeneous molecules exhibit full internal segregation of the component
      species. This macroscopic segregation can be inhibited by oppositely charging the
      two different molecular species. The degree of compatibility achieved by the
      charges leads to either fully homogenous mixtures or to local segregation and the
      possible formation of regular patterns. We investigate the induction of periodic
      surface patterns by the presence of opposite charges in flat films and
      cylindrical micelles. In the strong segregation limit the incompatibility between
      species can be described by a line tension parameter gamma. The size of the
      patterns formed is of the order of a characteristic size L approximately
      (gamma/sigma(2))(1/2), where sigma is the surface charge density. The pattern
      symmetry on flat surfaces is function only of the fraction of area covered by the
      components, f: lamellar for 0.34<f<0.66 and hexagonal otherwise. In cationic and
      anionic mixtures aggregated into cylindrical micelles the symmetry and size of
      the surface charged domains depends also on the radius R of the cylinder. For
      large radii the patterns are similar to those in the plane, but for small radii
      only lamellar patterns are formed. At high salt concentration the surface domain
      size jumps discontinuously to an infinite value, resulting in macroscopic phase
      segregation.

PMID- 15740354
TI  - From the double-stranded helix to the chiral nematic phase of B-DNA: a molecular
      model.
AB  - B-DNA solutions of suitable concentration form left-handed chiral nematic phases
      (cholesterics). Such phases have also been observed in solutions of other stiff
      or semiflexible chiral polymers; magnitude and handedness of the cholesteric
      pitch are uniquely related to the molecular features. In this work we present a
      theoretical method and a numerical procedure which, starting from the structure
      of polyelectrolytes, lead to the prediction of the cholesteric pitch. Molecular
      expressions for the free energy of the system are obtained on the basis of steric
      and electrostatic interactions between polymers; the former are described in
      terms of excluded volume, while a mean field approximation is used for the
      latter. Calculations have been performed for 130 base pair fragments of B-DNA.
      The theoretical predictions provide an explanation for the experimental behavior,
      by showing the counteracting role played by shape and charge chirality of the
      molecule.

PMID- 15740355
TI  - The dipole moments of the excited states of FeC.
AB  - With the purpose of comparing expectation dipole moment values mu with finite
      field obtained dipole moments mu(FF), we recalculated by the finite-field method
      previously reported mu values of 38 excited states of FeC. In most of the cases
      mu(FF) is significantly larger than mu.

PMID- 15740356
TI  - Comment on "A centroid molecular dynamics study of liquid para hydrogen and ortho
      deuterium" [J. Chem. Phys. 121, 6412 (2004)].
AB  - We show that the two phase points considered in the recent simulations of liquid
      para hydrogen by Hone and Voth lie in the liquid-vapor coexistence region of a
      purely classical molecular dynamics simulation. By contrast, their phase point
      for ortho deuterium was in the one-phase liquid region for both classical and
      quantum simulations. These observations are used to account for their report that
      quantum mechanical effects enhance the diffusion in liquid para hydrogen and
      decrease it in ortho deuterium.(c) 2005 American Institute of Physics.

PMID- 15740358
TI  - Full-dimensional vibrational calculations for H5O2+ using an ab initio potential
      energy surface.
AB  - We report quantum diffusion Monte Carlo (DMC) and variational calculations in
      full dimensionality for selected vibrational states of H(5)O(2) (+) using a new
      ab initio potential energy surface [X. Huang, B. Braams, and J. M. Bowman, J.
      Chem. Phys. 122, 044308 (2005)]. The energy and properties of the zero-point
      state are focused on in the rigorous DMC calculations. OH-stretch fundamentals
      are also calculated using "fixed-node" DMC calculations and variationally using
      two versions of the code MULTIMODE. These results are compared with infrared
      multiphoton dissociation measurements of Yeh et al. [L. I. Yeh, M. Okumura, J. D.
      Myers, J. M. Price, and Y. T. Lee, J. Chem. Phys. 91, 7319 (1989)]. Some
      preliminary results for the energies of several modes of the shared hydrogen are
      also reported.

PMID- 15740359
TI  - Emergence of a new feature in the high pressure-high temperature relaxation
      spectrum of tri-propylene glycol.
AB  - We investigated dielectric relaxation of a tri-propylene glycol system under high
      compression. By increasing temperature and pressure we observed that a new
      relaxation process emerges from the low frequency tail of the structural peak.
      This new peak starts to be visible at about 0.5 GPa and becomes clearly evident
      at 1.7 GPa. However, this additional peak merges again with the structural one as
      the glass transition is approached, since it has a weaker temperature dependence.
      This finding enriches the relaxation scenario of molecular glass formers
      confirming that the application of very high hydrostatic pressure can favor the
      detection of new relaxation or otherwise unresolved processes in supercooled
      liquid systems.

PMID- 15740360
TI  - Using fluorescence resonance energy transfer to measure distances along
      individual DNA molecules: corrections due to nonideal transfer.
AB  - Single molecule fluorescence resonance energy transfer has been extensively used
      to measure distance changes and kinetics in various biomolecular systems.
      However, due to complications involving multiple de-excitation pathways of the
      dyes, the absolute inter-dye distance information has seldom been recovered. To
      circumvent this we directly probe the relative variations in the quantum yield of
      individual fluorophores. B-DNA was used as a scaffold to position the donor (Cy3
      or TMR) at precise distances from the acceptor (Cy5) within the Forster radius.
      We found that the variation in the Cy3 quantum yield is approximately 5 times
      larger than that of TMR. By taking into account the molecule-to-molecule
      variability in the acceptor/donor quantum yield ratio, the apparent fluorescence
      resonance energy transfer efficiencies were scaled to yield the theoretical
      values. We obtained very good agreement with a physical model that predicts
      distances along B-DNA.

PMID- 15740361
TI  - Real-space post-Hartree-Fock correlation models.
AB  - Real-space models of nondynamical correlation between electrons of opposite spin
      and of parallel spin in multicenter (molecular) systems are discussed. These
      models are designed to be partnered with Hartree-Fock or exact Kohn-Sham
      exchange. Thus the numerous and well-known problems of local density-functional
      exchange-correlation approximations, especially in stretched odd-electron
      systems, are circumvented.

PMID- 15740362
TI  - Matching-pursuit/split-operator-Fourier-transform computations of thermal
      correlation functions.
AB  - A rigorous and practical methodology for evaluating thermal-equilibrium density
      matrices, finite-temperature time-dependent expectation values, and time
      correlation functions is described. The method involves an extension of the
      matching-pursuit/split-operator-Fourier-transform method to the solution of the
      Bloch equation via imaginary-time propagation of the density matrix and the
      evaluation of Heisenberg time-evolution operators through real-time propagation
      in dynamically adaptive coherent-state representations.

PMID- 15740363
TI  - Relativistic corrections to the diamagnetic term of the nuclear magnetic
      shielding: analysis of contributions from localized orbitals.
AB  - We have calculated the relativistic corrections to the diamagnetic term of the
      nuclear magnetic shielding constants for a series of molecules containing heavy
      atoms. An analysis of the contributions from localized orbitals is performed. We
      establish quantitatively the relative importance of inner core and valence shell
      molecular orbitals in each correcting term. Contributions from the latter are
      much less important than those from the former. The calculated values of the
      correction sigma(L-PSO), first derived within the linear response elimination of
      small component formalism, show a power-law dependence on the nuclear charge
      approximately Z(3.5), in contrast with the approximately Z(3.1) behavior of the
      mass-velocity external-field correction to the paramagnetic term previously
      reported.

PMID- 15740364
TI  - Connection between the regular approximation and the normalized elimination of
      the small component in relativistic quantum theory.
AB  - The regular approximation to the normalized elimination of the small component
      (NESC) in the modified Dirac equation has been developed and presented in matrix
      form. The matrix form of the infinite-order regular approximation (IORA)
      expressions, obtained in [Filatov and Cremer, J. Chem. Phys. 118, 6741 (2003)]
      using the resolution of the identity, is the exact matrix representation and
      corresponds to the zeroth-order regular approximation to NESC (NESC-ZORA).
      Because IORA (=NESC-ZORA) is a variationally stable method, it was used as a
      suitable starting point for the development of the second-order regular
      approximation to NESC (NESC-SORA). As shown for hydrogenlike ions, NESC-SORA
      energies are closer to the exact Dirac energies than the energies from the fifth
      order Douglas-Kroll approximation, which is much more computationally demanding
      than NESC-SORA. For the application of IORA (=NESC-ZORA) and NESC-SORA to many
      electron systems, the number of the two-electron integrals that need to be
      evaluated (identical to the number of the two-electron integrals of a full Dirac
      Hartree-Fock calculation) was drastically reduced by using the resolution of the
      identity technique. An approximation was derived, which requires only the two
      electron integrals of a nonrelativistic calculation. The accuracy of this
      approach was demonstrated for heliumlike ions. The total energy based on the
      approximate integrals deviates from the energy calculated with the exact
      integrals by less than 5 x 10(-9) hartree units. NESC-ZORA and NESC-SORA can
      easily be implemented in any nonrelativistic quantum chemical program. Their
      application is comparable in cost with that of nonrelativistic methods. The
      methods can be run with density functional theory and any wave function method.
      NESC-SORA has the advantage that it does not imply a picture change.

PMID- 15740365
TI  - Analytical time-dependent density functional derivative methods within the RI-J
      approximation, an approach to excited states of large molecules.
AB  - Time-dependent density functional theory (TDDFT) is now well established as an
      efficient method for molecular excited state treatments. In this work, we
      introduce the resolution of the identity approximation for the Coulomb energy (RI
      J) to excited state gradient calculations. In combination with nonhybrid
      functionals, the RI-J approximation leads to speed ups in total timings of an
      order of magnitude compared to the conventional method; this is demonstrated for
      oligothiophenes with up to 40 monomeric units and adamantane clusters. We assess
      the accuracy of the computed adiabatic excitation energies, excited state
      structures, and vibrational frequencies on a set of 36 excited states. The error
      introduced by the RI-J approximation is found to be negligible compared to
      deficiencies of standard basis sets and functionals. Auxiliary basis sets
      optimized for ground states are suitable for excited state calculations with
      small modifications. In conclusion, the RI-J approximation significantly extends
      the scope of applications of analytical TDDFT derivative methods in photophysics
      and photochemistry.

PMID- 15740366
TI  - The influence of intense control laser pulses on homodyne-detected rotational
      wave packet dynamics in O2 by degenerate four-wave mixing.
AB  - We illustrate how the preparation and probing of rotational Raman wave packets in
      O(2) detected by time-dependent degenerate four-wave mixing (TD-DFWM) can be
      manipulated by an additional time-delayed control pulse. By controlling the time
      delay of this field, we are able to induce varying amounts of additional Rabi
      cycling among multiple rotational states within the system. The additional Rabi
      cycling is manifested as a change in the signal detection from homodyne detected
      to heterodyne detected, depending on the degree of rotational alignment induced.
      At the highest laser intensities, Rabi cycling among multiple rotational states
      cannot account for the almost complete transformation to a heterodyne-detected
      signal, suggesting a second mechanism involving ionization. The analysis we
      present for these effects, involving the formation of static alignment by Rabi
      cycling at moderate laser intensities and possibly ion gratings at the highest
      intensities, appears to be consistent with the experimental findings and may
      offer viable explanations for the switching from homodyne to heterodyne detection
      observed in similar DFWM experiments at high laser field intensities (>10(13)
      W/cm(2)).

PMID- 15740367
TI  - Multiphoton photodetachment of C60-.
AB  - A model delta-function potential is considered for simulating the interaction of
      the attached electron in C(60) (-) with the fullerene environment. The analytical
      expressions for the energy eigenstates, and the Green's function, are used to
      deduce the one-, two-, and three-photon photodetachment probabilities for C(60) (
      ). Particularly interesting is the observation that the three-photon
      photodetachment is greatly enhanced by the bound states with energies close to
      the energies for resonant absorption of one and two photons, and a resonance in
      the l=3 state.

PMID- 15740368
TI  - Radical-molecule reaction C3H+H2O: a mechanistic study.
AB  - Despite the importance of the C(3)H radical in both combustion and interstellar
      space, the reactions of C(3)H toward stable molecules have never been studied. In
      this paper, we report our detailed mechanistic study on the radical-molecule
      reaction C(3)H+H(2)O at the Becke's three parameter Lee-Yang-Parr-B3LYP6
      311G(d,p) and coupled cluster with single, double, and triple excitations
      CCSD(T)6-311G(2d,p) (single-point) levels. It is shown that the C(3)H+H(2)O
      reaction initially favors formation of the carbene-insertion intermediates
      HCCCHOH (1a,1b) rather than the direct H- or OH-abstraction process.
      Subsequently, the isomers (1a,1b) can undergo a direct H- extrusion to form the
      well-known product propynal HCCCHO (P(5)). Highly competitively, (1a,1b) can take
      the successive 1,4- and 1,2-H-shift interconversion to isomer H(2)CCCHO(2a,2b)
      and then to isomer H(2)CCHCO(3a,3b), which can finally take a direct C-C bond
      cleavage to give product C(2)H(3) and CO (P(1)). The other products are
      kinetically much less feasible. With the overall entrance barrier 10.6 kcal/mol,
      the title reaction can be important in postburning processes. Particularly, our
      calculations suggest that the title reaction may play a role in the formation of
      the intriguing interstellar molecule, propynal HCCCHO. The calculated results
      will also be useful for the analogous C(3)H reactions such as with ammonia and
      alkanes.

PMID- 15740369
TI  - 4d-->4f dipole resonance of the metal atom encapsulated in a fullerene cage:
      Ce@C82.
AB  - The yield curves for photoions from Ce@C(82) are measured by using synchrotron
      radiation in the photon energy range from 90 to 160 eV. Parent Ce@C(82) (z+) and
      fragment ions C(60) (z+) and C(70) (z+) are observed in a mass spectrum (z=1 and
      2). The yield curves for doubly charged ionic species exhibit broad resonance in
      the photon energy region of from 120 to 140 eV which is ascribed to the 4d-->4f
      giant dipole resonance of the encapsulated Ce atom. The total photoabsorption
      cross section of Ce@C(82) was determined from partial photoionization cross
      sections for formation of the parent and fragment ions to be 5.3(-1.1) (+1.8) and
      19.6(-3.9) (+6.5) Mb at photon energies of 110 and 130 eV, respectively.

PMID- 15740370
TI  - Wave packet dynamics of H2(v1=8-14)+H2(v2=0-2): the role of the potential energy
      surface on different reactive and dissociative processes.
AB  - A time-dependent wave packet method has been used to study different competing
      products of H(2)+H(2) collisions: four center reaction, collision induced
      dissociation, reactive dissociation, and three-body complex formation. A three
      degree-of-freedom reduced dimensionality model has been used for five different
      geometries of the colliding complex (parallel H, crossed X, collinear L, and two
      T-shaped geometries T(I) and T(II)), with reactants in selected vibrational
      states with one diatom vibrationally "hot" and the other one vibrationally
      "cold." Product probabilities have been calculated using two potential energy
      surfaces [J. Chem. Phys. 101, 4004 (1994); J. Chem. Phys. 116, 666 (2002)] in
      order to compare their performance in the dynamics. The regions of the potential
      energy surfaces responsible of the threshold behavior of the probabilities have
      been identified. Overall, we have found that the most recent potential energy
      surface is less anisotropic, provides a smaller propensity for insertion-type
      processes, and gives lower energy thresholds.

PMID- 15740371
TI  - Theoretical interpretation of the line shape of the gaseous acetic acid cyclic
      dimer.
AB  - A general quantum theoretical approach of the nu(X-H) IR line shape of cyclic
      dimers of weakly H-bonded species in the gas phase is proposed. In this model,
      the adiabatic approximation (allowing to separate the high frequency motion from
      the slow one of the H-bond bridge), is performed for each separate H-bond bridge
      of the dimer and a strong nonadiabatic correction is introduced into the model
      via the resonant exchange between the fast mode excited states of the two
      moieties. The present model reduces satisfactorily to many models in the
      literature dealing with more special situations. It has been applied to the
      cyclic dimers (CD(3)CO(2)H)(2) and (CD(3)CO(2)D)(2) in the gas phase. It
      correctly fits the experimental line shape of the hydrogenated compound and
      predict satisfactorily the evolution in the line shapes, to the deuterated one by
      reducing simply the angular frequency of the H-bond bridge and the anharmonic
      coupling parameter by the factor 1/ square root of 2.

PMID- 15740372
TI  - Rotational state-resolved reaction cross section in the reactions of state
      selected CH with NO and with O2.
AB  - A pure and highly intense state-selected pulsed supersonic CH(X (2)Pi) radical
      beam source was developed by use of the C((1)D)+H(2) reaction with the
      combination of the state selection and purification by an electrostatic hexapole
      field. Under the beam-cell condition, the elementary reactions of CH+NO and
      CH+O(2) were studied by using this state-selected CH beam. NH(A (3)Pi) [and NCO(A
      (2)Sigma(+))] formations and OH(A (2)Sigma(+)) formation were directly identified
      in the elementary reaction of CH+NO and CH+O(2), respectively. For the CH+NO
      reaction, the relative branching ratio sigma(NCO*)sigma(NH) of NCO(A (2)Sigma(+))
      formation to NH(A (3)Pi) formation was determined to be 0.35+/-0.15. The state
      selected reaction cross sections were determined for each rotational state of CH.
      In the CH+NO reaction, a remarkable rotational state dependence of the reactive
      cross section was revealed, while the CH+O(2) reaction showed little rotational
      state dependence.

PMID- 15740373
TI  - Electronically forbidden (5sigmau-->ksigmau) photoionization of CS2: mode
      specific electronic-vibrational coupling.
AB  - Vibrationally resolved photoelectron spectroscopy of the CS(2) (+)(B (2)Sigma(u)
      (+)) state is used to show how nontotally symmetric vibrations "activate" a
      forbidden electronic transition in the photoionization continuum, specifically, a
      5sigma(u)-->ksigma(u) shape resonance, that would be inaccessible in the absence
      of a symmetry breaking vibration. This electronic channel is forbidden owing to
      inversion symmetry selection rules, but it can be accessed when a nonsymmetric
      vibration is excited, such as bending or antisymmetric stretching. Photoelectron
      spectra are acquired for photon energies 17</=hnu</=72 eV, and it is observed
      that the forbidden vibrational transitions are selectively enhanced in the region
      of a symmetry-forbidden continuum shape resonance centered at hnu approximately
      42 eV. Schwinger variational calculations are performed to analyze the data, and
      the theoretical analysis demonstrates that the observed forbidden transitions are
      due to photoelectron-mediated vibronic coupling, rather than interchannel
      Herzberg-Teller mixing. We observe and explain the counterintuitive result that
      some vibrational branching ratios vary strongly with energy in the region of the
      resonance, even though the resonance position and width are not appreciably
      influenced by geometry changes that correspond to the affected vibrations. In
      addition, we find that another resonant channel, 5sigma(u)-->kpi(g), influences
      the symmetric stretch branching ratio. All of the observed effects can be
      understood within the framework of the Chase adiabatic approximation, i.e., the
      Born-Oppenheimer approximation applied to photoionization.

PMID- 15740374
TI  - Calculating energy levels of isomerizing tetra-atomic molecules. II. The
      vibrational states of acetylene and vinylidene.
AB  - A general, full-dimensional computational method for the accurate calculation of
      rotationally and vibrationally excited states of tetra-atomic molecules is
      further developed. The resulting computer program may be run in serial and
      parallel modes and is particularly appropriate for molecules executing wide
      amplitude motions and isomerizations. An application to the isomerizing
      acetylene/vinylidene system is presented. Large-scale calculations using a
      coordinate system based on orthogonal satellite vectors have been performed in
      six dimensions and vibrational term values and wave functions for acetylene and
      vinylidene states up to approximately 23 000 cm(-1) above the potential minimum
      have been determined. This has permitted the characterization of acetylene and
      vinylidene states at and above the isomerization barrier. These calculations
      employ more extensive vibrational basis sets and hence consider a much higher
      density of states than in any variational calculations reported hitherto for this
      system. Comparison of the calculated density of states with that determined
      empirically suggests that our calculations are the most realistic achieved for
      this system to date. Indeed more states have been converged than in any previous
      study of this system. Calculations on lower lying excited states of acetylene
      based on HC-CH diatom-diatom coordinates give nearly identical results to those
      based on orthogonal satellite vectors. Comparisons are also made with
      calculations based on HH-CC diatom-diatom coordinates.

PMID- 15740375
TI  - Superexchange and electron correlations in alkali fullerides AC60, A=K, Rb, Cs.
AB  - Superexchange interactions in alkali fullerides AC(60) are derived for C(60)
      molecular ions separated by interstitial alkali-metal ions. We use a
      multiconfiguration approach which comprises the lowest molecular orbital states
      of the C(60) molecule and the excited s and d states of the alkali-metal atom A.
      Interactions are described by the valence bond (Heitler-London) method for a
      complex (C(60)-A-C(60))(-) with two valence electrons. The electronic charge
      transfer between the alkali-metal atom and a neighboring C(60) molecule is not
      complete. The occupation probability of excited d and s states of the alkali atom
      is not negligible. In correspondence with the relative positions of the C(60)
      molecules and A atoms in the polymer crystal, we consider 180 degrees and 90
      degrees (angle) superexchange pathways. For the former case the ground state is
      found to be a spin singlet separated from a triplet at approximately 20 K. For
      T<20 K there appear strong spin correlations for the 180 degrees superexchange
      pathway. The results are related to spin lattice relaxation experiments on
      CsC(60) in the polymerized and in the quenched cubic phase.

PMID- 15740376
TI  - Remarkable interplay of electron correlation and relativity in the
      photodetachment spectrum of PtCl(6)2-.
AB  - In this work we calculate the photoelectron spectrum of the PtCl(6) (2-) dianion
      by application of the recently developed third-order Dirac-Hartree-Fock
      implementation of the one-particle propagator technique allowing for a consistent
      treatment of spin-orbit and scalar relativistic effects together with electron
      correlation. For PtCl(6) (2-) a gas phase photoelectron spectrum is available
      showing clearly discernible structures not reproducible by a nonrelativistic or
      purely scalar-relativistic computation. A population analysis of the valence
      orbitals allows for an assignment of the photoelectron peaks and reveals the
      strong influence of relativity in combination with electron correlation.

PMID- 15740377
TI  - Improved modification for the density-functional theory calculation of
      thermodynamic properties for C-H-O composite compounds.
AB  - A three-parametric modification equation and the least-squares approach are
      adopted to calibrating hybrid density-functional theory energies of C(1)-C(10)
      straight-chain aldehydes, alcohols, and alkoxides to accurate enthalpies of
      formation DeltaH(f) and Gibbs free energies of formation DeltaG(f), respectively.
      All calculated energies of the C-H-O composite compounds were obtained based on
      B3LYP6-311++G(3df,2pd) single-point energies and the related thermal corrections
      of B3LYP6-31G(d,p) optimized geometries. This investigation revealed that all
      compounds had 0.05% average absolute relative error (ARE) for the atomization
      energies, with mean value of absolute error (MAE) of just 2.1 kJ/mol (0.5
      kcal/mol) for the DeltaH(f) and 2.4 kJ/mol (0.6 kcal/mol) for the DeltaG(f) of
      formation.

PMID- 15740378
TI  - Inelastic collisions in para-H2: translation-rotation state-to-state rate
      coefficients and cross sections at low temperature and energy.
AB  - We report an experimental determination of the k(00-->02) rate coefficient for
      inelastic H(2):H(2) collisions in the temperature range from 2 to 110 K based on
      Raman spectroscopy data in supersonic expansions of para-H(2). For this purpose a
      more accurate method for inverting the master equation of rotational populations
      is presented. The procedure permits us to reduce the measured k(00-->02) rate
      coefficient to the corresponding sigma(00-->02) cross section in the range of
      precollisional energy from 360 to 600 cm(-1). Numerical calculations of sigma(00-
      >02) carried out in the frame of the coupled channel method are also reported for
      different intermolecular potentials of H(2). A good agreement is found between
      the experimental cross section and the numerical one derived from Diep and
      Johnson's potential [J. Chem. Phys. 112, 4465 (2000)].

PMID- 15740379
TI  - Hydrated copper and gold monovalent cations: Ab initio study.
AB  - To understand the hydration phenomena of noble transition metals, we investigated
      the structures, hydration energies, electronic properties, and spectra of the
      Cu(+)(H(3)O)(1-6) and Au(+)(H(2)O)(1-6) clusters using ab initio calculations.
      The coordination numbers of these clusters are found to be only two, which is
      highly contrasted to those of Ag(+)(H(2)O)(n) (which have the coordination
      numbers of 3-4) as well as the hydrated alkali metal ions (which have the
      coordination numbers of approximately 6). For the possible identification of
      their interesting hydration structures, we predict their IR spectra for the OH
      stretch modes.

PMID- 15740380
TI  - High accuracy ab initio studies of Li6+, Li6-, and three isomers of Li6.
AB  - The structures and energetics of Li(6) (+), Li(6) (-) and three isomers of Li(6)
      are investigated using the coupled-cluster singles, doubles and perturbative
      triples [CCSD(T)] method with valence and core-valence correlation consistent
      basis sets of double- to quadruple-zeta quality (cc-pVXZ and cc-pCVXZ, where X=D
      Q). These results are compared with qualitatively different predictions by less
      reliable methods. Our results conclusively show that the D(4h) isomer is the
      global minimum structure for Li(6). It is energetically favored over the C(5v)
      and D(3h) structures by about 5.1 and 7.1 kcal mol(-1), respectively, after the
      inclusion of the zero-point vibrational energy (ZPVE) correction. Our most
      accurate total atomization energies are 123.2, 117.6, and 115.7 kcal mol(-1) for
      the D(4h), C(5v), and D(3h) isomers, respectively. Comparison of experimental
      optical absorption spectra with our computed electronic spectra also indicate
      that the D(4h) isomer is indeed the most stable structure. The cation, anion, and
      some higher spin states are investigated using the less expensive cc-pCVDZ basis
      set. Adiabatic ionization energies and electron affinities are reported and
      compared with experimental values. Predictions of molecular properties are found
      to be sensitive to the basis set used and to the treatment of electron
      correlation.

PMID- 15740381
TI  - The energetics and structural properties of diazomethyl (HCNN) and cyanomidyl
      (HNCN) radicals and their related cations and anions from ab initio calculations.
AB  - The molecular structures and energetics of diazomethyl (HCNN) and cyanomidyl
      (HNCN) radicals and their related cations (HCNN(+),HNCN(+)) and anions (HCNN(
      ),HNCN(-)) are reported at a high level of accuracy. The singles and doubles
      coupled-cluster method including a perturbational correction for connected triple
      excitations with systematic sequences of correlation consistent basis sets have
      been employed. Extrapolation to the complete basis set limit has been used with
      accurate treatments of core-valence correlation effects in order to accurately
      predict molecular properties, ionization potentials, electron affinities as well
      as C-H and N-H bond dissociation energies. For all the species studied, harmonic
      vibrational frequencies have also been evaluated in order to obtain zero-point
      corrections to ionization potentials, electron affinities, and dissociation
      energies.

PMID- 15740382
TI  - Effect of the excitation pulse frequency on the ultrafast photoinduced electron
      transfer dynamics.
AB  - The dependence of the ultrafast photoinduced electron transfer dynamics in donor
      acceptor complexes on the excitation pulse carrier frequency (spectral effect)
      has been investigated in the framework of a model involving three electronic
      state. The spectral effect has been shown to strongly depend on the angle theta
      between the reaction coordinate directions corresponding to optical and charge
      transfer transitions. Describing the solvent as a linear homogenous polar medium
      and accounting for Coulombic interaction of the transferred charge with the
      medium polarization fluctuations, the angle theta has been found out to be
      typically in the area 40 degrees -85 degrees. Exactly in this area of theta the
      spectral effect is predicted to be most pronounced.

PMID- 15740383
TI  - Dressed ion theory of size-asymmetric electrolytes: effective ionic charges and
      the decay length of screened Coulomb potential and pair correlations.
AB  - The effects of ionic size asymmetry on long-range electrostatic interactions in
      electrolyte solutions are investigated within the primitive model. Using the
      formalism of dressed ion theory we analyze correlation functions from Monte Carlo
      simulations and the hypernetted chain approximation for size asymmetric 1:1
      electrolytes. We obtain decay lengths of the screened Coulomb potential,
      effective charges of ions, and effective permittivity of the solution. It is
      found that the variation of these quantities with the degree of size asymmetry
      depends in a quite intricate manner on the interplay between the electrostatic
      coupling and excluded volume effects. In most cases the magnitude of the
      effective charge of the small ion species is larger than that of the large
      species; the difference increases with increasing size asymmetry. The effective
      charges of both species are larger (in absolute value) than the bare ionic
      charge, except for high asymmetry where the effective charge of the large ions
      can become smaller than the bare charge.

PMID- 15740384
TI  - Analysis of the validity of perturbation density functional theory: based on
      extensive simulation for simple fluid at supercritical and subcritical
      temperature under various external potentials.
AB  - Because of the scarcity of available simulation data for confined hard-core
      attractive Yukawa model fluid, extensive Monte Carlo (MC) simulation research for
      this fluid under the influence of various external potentials were carried out.
      The present MC simulation results were employed to test a performance of the
      third-order perturbation density functional theory (DFT) based on a high order
      direct correlation function (DCF) [S. Zhou and E. Ruckenstein, Phys. Rev. E. 61,
      2704 (2000)]. It was found that the present perturbation DFT formalism is soundly
      structured only if the imported second-order DCF is reliable. In this case, the
      accuracy of the results can be satisfactory or even very high for various types
      of external potentials. Further, the associated adjustable parameter can be
      universal, i.e., independent of the particular external field responsible for the
      generation of a nonuniform density profile. Dependence of both the maintenance of
      the reliability of the formalism and holding of the universality of the
      adjustable parameter on the accuracy of the imported bulk second-order DCF can be
      strengthened by the large difference between the external field investigated and
      that caused by a single hard wall used for specification of the adjustable
      parameter. In case the gaseous density in the subcritical region is below the
      coexistence density, an excellent performance of the present formalism is
      observed even for the mean spherical approximation's second-order DCF as an
      input. This advantageous property, combined with the fact that the present
      formalism needs only the second-order DCF of fluid at the coexistence state as an
      input, enables the present formalism to be a very good theoretical tool for the
      investigations of wetting and prewetting transitions.

PMID- 15740385
TI  - Cascading third-order Raman process and local structure formation in binary
      liquid mixtures of benzene and n-hexane.
AB  - The cascading third-order Raman process in binary mixtures of benzene and n
      hexane was studied by six-wave mixing coherent anti-Stokes Raman scattering
      spectroscopy. By examining the concentration dependence of the cascading third
      order signal intensity, we investigated the formation of local structures of
      benzene in the binary mixtures. A significant deviation from the dependence
      expected for homogeneous mixtures was observed at benzene concentrations above 7
      mol dm(-3). This deviation can be interpreted in terms of optical inhomogeneity
      caused by the formation of domain structures of benzene molecules. We discuss the
      feasibility of the cascading third-order process as a sensitive probe for the
      microscopic structures that are formed in liquids and solutions.

PMID- 15740386
TI  - Neutron scattering study of the H-bond network in amorphous N-methylformamide.
AB  - Original investigations of structural properties in noncrystalline solid N
      methylformamide (HCONHCH(3)) are presented in this paper. After description of
      the sample preparation, the elastic neutron scattering formalism is applied to
      deduce the coherent scattering cross section for amorphous N-methylformamide. The
      contribution of each possible monomer (cis or trans) is computed and the
      corresponding distinct structure factor is deduced. Our measurements clearly show
      that the hydrogen-bond network occurs in amorphous N-methylformamide between C=O
      and N-H groups. The experimental spectra are consistent with an open-chain
      structure similar to the one existing in the crystalline form. The more probable
      clusters that have been identified in the liquid are also examined.

PMID- 15740387
TI  - A comparison between different semiclassical approximations for optical response
      functions in nonpolar liquid solutions.
AB  - The temporal behavior of optical response functions (ORFs) reflects the quantum
      dynamics of an electronic superposition state, and as such lacks a well-defined
      classical limit. In this paper, we consider the importance of accounting for the
      quantum nature of the dynamics when calculating ORFs of different types. To this
      end, we calculated the ORFs associated with the linear absorption spectrum and
      the nonlinear two-pulse photon-echo experiment, via the following approaches: (1)
      the semiclassical forward-backward approach; (2) an approach based on linearizing
      the path-integral forward-backward action in terms of the difference between the
      forward and backward paths; (3) an approach based on ground state nuclear
      dynamics. The calculations were performed on a model that consists of a two-state
      chromophore solvated in a nonpolar liquid. The different methods were found to
      yield very similar results for the absorption spectrum and "diagonal" two-pulse
      photon echo (i.e., the homodyne-detected signal at time t=t(0) after the second
      pulse, where t(0) is the time interval between the two pulses). The different
      approximations yielded somewhat different results in the case of the time
      integrated photon-echo signal. The reasons for the similarity between the
      predictions of different approximations are also discussed.

PMID- 15740388
TI  - Stability limits in binary fluids mixtures.
AB  - The stability limits in binary fluid mixtures are investigated on the basis of
      the global phase diagram approach employing a model for the attracting hard
      sphere fluid. In addition to the diffusion spinodals the mechanical spinodals are
      included. As a result one finds topologically different types of the diffusion
      spinodals while only one shape exists for the mechanical spinodals which are
      present in the region of liquid-vapor equilibria only. The diffusion spinodals
      represent the underlying properties of the phase behavior. The types of stable
      phase behavior therefore resemble that of the spinodal behavior. The different
      shapes of the spinodals can be important for nonequilibrium processes in nature
      and technology.

PMID- 15740389
TI  - Determination of fluid-phase behavior using transition-matrix Monte Carlo: binary
      Lennard-Jones mixtures.
AB  - We present a novel computational methodology for determining fluid-phase
      equilibria in binary mixtures. The method is based on a combination of highly
      efficient transition-matrix Monte Carlo and histogram reweighting. In particular,
      a directed grand-canonical transition-matrix Monte Carlo scheme is used to
      calculate the particle-number probability distribution, after which histogram
      reweighting is used as a postprocessing procedure to determine the conditions of
      phase equilibria. To validate the methodology, we have applied it to a number of
      model binary Lennard-Jones systems known to exhibit nontrivial fluid-phase
      behavior. Although we have focused on monatomic fluids in this work, the method
      presented here is general and can be easily extended to more complex molecular
      fluids. Finally, an important feature of this method is the capability to predict
      the entire fluid-phase diagram of a binary mixture at fixed temperature in a
      single simulation.

PMID- 15740390
TI  - Energy levels in self-assembled quantum arbitrarily shaped dots.
AB  - A model to determine the electronic structure of self-assembled quantum
      arbitrarily shaped dots is applied. This model is based principally on constant
      effective mass and constant potentials of the barrier and quantum dot material.
      An analysis of the different parameters of this model is done and compared with
      those which take into account the variation of confining potentials, bands, and
      effective masses due to strain. The results are compared with several spectra
      reported in literature. By considering the symmetry, the computational cost is
      reduced with respect to other methods in literature. In addition, this model is
      not limited by the geometry of the quantum dot.

PMID- 15740391
TI  - Amorphous-amorphous transition in glassy polymers subjected to cold rolling
      studied by means of positron annihilation lifetime spectroscopy.
AB  - In this study, polycarbonate (PC) and polystyrene (PS) are subjected to plastic
      deformation by means of cold rolling and the resulting variation of the free
      volume and its subsequent time evolution after rolling is investigated by means
      of positron annihilation lifetime spectroscopy (PALS). The value of the long
      lifetime component that is attributed to the decay of ortho-positronium (tau(o
      Ps)) and its intensity (I(o-Ps)) are used to characterize, respectively, the size
      and the concentration of the free-volume holes. In addition to the PALS
      experiments, the effect of plastic deformation on the dynamic tensile modulus is
      investigated. The PALS results show that both for well-aged PC and PS an increase
      of tau(o-Ps) and a decrease of I(o-Ps) occur upon plastic deformation. During the
      subsequent aging, tau(o-Ps) tends to return to the value assumed before plastic
      deformation, while I(o-Ps) remains constant with time. These results corroborate
      the idea of an amorphous-amorphous transition, rather than that of a "mechanical
      rejuvenation" as proposed in the past to explain the ability of plastic
      deformation to reinitiate physical aging. Finally, a linear relation between the
      size of the free-volume holes and the dynamic tensile modulus is found, which
      suggests that the stiffness of amorphous glassy polymers is fully determined by
      their nanoscopic structure.

PMID- 15740392
TI  - Oil-in-water microemulsions stabilized by charged diblock copolymers.
AB  - We present here oil-in-water microemulsions stabilized by charged diblock
      copolymers alone, along with their structural characterization by small-angle
      neutron scattering measurements. They consist of swollen spherical micelles
      containing small amounts of oil in their core, which is surrounded by a corona of
      stretched polyelectrolyte chains. Structural changes, including core size
      variations, are evidenced when using a cosurfactant, or upon addition of salt,
      through a contraction of the charged corona. Attempts to relate the micellar
      structure to the individual copolymer characteristics are also presented, and
      show that the size of the hydrophobic block mainly determines that of the
      micelles.

PMID- 15740393
TI  - Defect-assisted conductivity in organic ionic plastic crystals.
AB  - In order to determine the role of defects (vacancies and extended lattice
      defects) in the conductivity mechanism of a well studied organic ionic plastic
      crystal electrolyte, conductivity and mean defect volumes were measured. The
      ionic conductivity of the salt showed a characteristic phase dependence. Defect
      volumes, as measured by positron annihilation lifetime spectroscopy, showed
      increasing rates of expansion with increasing rotational disorder. The dependence
      of ionic conductivity on defect volume was observed to be phase dependent.
      Increases in mean defect volume size below approximately 100 cm(3) mol(-1) did
      not always facilitate ionic conductivity. It was shown that the material
      undergoes a solid-solid phase transition to the most disordered phase (a plastic
      crystalline phase with the highest conductivity) when the mean defect volume
      becomes larger than the molar volume of either the rotating anionic or cationic
      species. Conductivity in this phase had the strongest dependence on defect
      volume. Critical volumes calculated from the free volume model of Cohen and
      Turnbull were unrealistically large.

PMID- 15740394
TI  - Effects of lateral diffusion on morphology and dynamics of a microscopic lattice
      gas model of pulsed electrodeposition.
AB  - The influence of nearest-neighbor diffusion on the decay of a metastable low
      coverage phase (monolayer adsorption) in a square lattice-gas model of
      electrochemical metal deposition is investigated by kinetic Monte Carlo
      simulations. The phase-transformation dynamics are compared to the well
      established Kolmogorov-Johnson-Mehl-Avrami theory. The phase transformation is
      accelerated by diffusion, but remains in accord with the theory for continuous
      nucleation up to moderate diffusion rates. At very high diffusion rates the phase
      transformation kinetic shows a crossover to instantaneous nucleation. Then, the
      probability of medium-sized clusters is reduced in favor of large clusters. Upon
      reversal of the supersaturation, the adsorbate desorbs, but large clusters still
      tend to grow during the initial stages of desorption. Calculation of the free
      energy of subcritical clusters by enumeration of lattice animals yields a
      quasiequilibrium distribution which is in reasonable agreement with the
      simulation results. This is an improvement relative to classical droplet theory,
      which fails to describe the distributions, since the macroscopic surface tension
      is a bad approximation for small clusters.

PMID- 15740395
TI  - Optical transverse excitation in quaterthiophene crystals by ultraviolet-visible
      internal and attenuated total reflection.
AB  - We report internal and attenuated total reflection of light at the interface
      between glass and a quaterthiophene crystal in the spectral region of the
      electronic transitions. The bands corresponding to the absorption of the a(u) and
      b(u) Frenkel exciton states are detected for different polarization of the
      incident light. In particular, the wave-normal vector being almost perpendicular
      to the b(u) transition dipole moment allows its transverse component to be
      accessed, whose excitation in conventional external reflection or transmission
      spectroscopies is forbidden.

PMID- 15740396
TI  - Lattice vibrations in cubic, tetragonal, and monoclinic phases of ZrO2.
AB  - First principles calculations of the phonon dispersion relations and the phonon
      density of states for three zero-pressure zirconia phases are presented. The
      phonon dispersion relations of the tetragonal and monoclinic phases do not
      exhibit the imaginary frequencies, contrary to the cubic phase for which the
      imaginary soft mode is seen. For tetragonal and monoclinic phases the free
      energies versus temperature are calculated in harmonic approximation. They cross
      at 1560 K indicating the phase transition.

PMID- 15740397
TI  - On the correlation between surface roughness and work function in copper.
AB  - Both surface roughness (SR) and work function (WF) are important characteristics
      of a solid surface. Understanding the relationship between SR and WF is necessary
      in order to apply the Kelvin probe technique to characterize surface behavior. In
      this study, SR and WF of copper surfaces were measured using atomic force
      microscopy and scanning Kelvin probe, respectively. Experimental results showed
      that WF decreased with increase of SR. Using sine functions, a capacitor model
      was proposed and a correlation between WF and SR was established. The theoretical
      predictions of WF were in good agreement with experimental results. The model is
      also useful for analyzing the effect of tip geometry on measurements of WF.

PMID- 15740398
TI  - Ice nucleation on BaF2(111).
AB  - The mechanism of heterogeneous ice nucleation on inorganic substrates is not well
      understood despite work on AgI and other materials over the past 50 years. We
      have selected BaF(2) as a model substrate for study since its (111) surface makes
      a near perfect match with the lattice of the basal face of I(h) ice and would
      appear to be an ideal nucleating agent. Two series of experiments were
      undertaken. In one, nucleation of thin film water formed from deposition of vapor
      on BaF(2)(111) faces was explored with the finding that supercooling to -30
      degrees C was required before freezing occurred. In the other series, nucleation
      of liquid water on submerged BaF(2) crystals was studied. Here supercooling to 
      15 degrees C was needed before ice formed. The reason why BaF(2) is such a poor
      nucleating agent contains clues to realistic mechanisms of heterogeneous
      nucleation. Our explanation of these results follows the model of Fletcher [J.
      Chem. Phys. 29, 572 (1958)] who showed that heterogeneous ice nucleating ability
      depends on how well ice wets a substrate. In this view, a smooth BaF(2)(111) face
      is poor at nucleation because ice only partially wets its surface. In an
      extension of Fletcher's model, our calculations, consistent with the experimental
      results demonstrate that the pitting of a submerged BaF(2) crystal dramatically
      improves its ice nucleating ability.

PMID- 15740399
TI  - Tetra-t-butyl magnesium phthalocyanine on gold: electronic structure and
      molecular orientation.
AB  - In this work we have investigated the electronic structure and the molecular
      orientation of (t-Bu)(4)PcMg (tetra-t-butyl magnesium phthalocyanine) on
      polycrystalline and single crystalline gold substrates using photoemission
      spectroscopy and x-ray absorption spectroscopy, and we compare the results to the
      unsubstituted PcCu (copper phthalocyanine). The C 1s photoemission spectrum is
      described similar to unsubstituted relatives with an additional component for the
      aliphatic substituents. The variation of the excitation energy causes distinct
      differences in the shape of the C 1s spectrum, which is very useful for the
      analysis of the molecular orientation in the uppermost layer. It is shown that
      despite of the sterically demanding substituents, ordered sublimed films of (t
      Bu)(4)PcMg are accessible, the orientation of the molecules, however, is
      different from the orientation of the unsubstituted relatives.

PMID- 15740400
TI  - Application of the constrained fluid lambda-integration path to the calculation
      of high temperature Au(110) surface free energies.
AB  - Recently a method termed constrained fluid lambda-integration was proposed for
      calculating the free energy difference between bulk solid and liquid reference
      states via the construction of a reversible thermodynamic integration path;
      coupling the two states in question. The present work shows how the application
      of the constrained fluid lambda-integration concept to solid/liquid slab
      simulation cells makes possible a generally applicable computer simulation
      methodology for calculating the free energy of any surface and/or surface defect
      structure, including surfaces requiring variations in surface atom or density
      number, such as the (1 x 5) Au(100) or (1 x 2) missing row Au(110) reconstructed
      surfaces or excess adatom/vacancy/step populated surfaces. We evaluate the
      methodology by calculating the free energy of various disordered high temperature
      Au(110) embedded atom method surfaces constrained to differing excess surface
      atom numbers [including those corresponding to the (1 x 2) missing row
      reconstructed surface] and obtained the interesting result that at 1000 K (as
      distinct from lower temperatures) the free energy difference between these
      surfaces is reduced to zero; a result which is consistent with an expected order
      disorder phase transition for the Au(110) surface at such high temperatures.

PMID- 15740401
TI  - Growth and sintering of Pd clusters on alpha-Al2O3(0001).
AB  - The growth and sintering of Pd nanoparticles on alpha-Al(2)O(3)(0001) have been
      studied by noncontact atomic force microscopy (NC-AFM), low-energy ion scattering
      spectroscopy (LEIS), temperature-programmed desorption (TPD) and x-ray
      photoelectron spectroscopy (XPS). This is the first study of metal nanoparticles
      on a well-defined oxide surface where both NC-AFM and LEIS are used for
      characterization. These prove to be a powerful combination in assessing particle
      dimensions. The clean alumina surface showed atomically flat, 200-700 nm wide
      terraces. The sharp step edges are straight (within our resolution) for lengths
      of >300 nm and have heights in multiples of 0.2 nm. The Pd grows initially as two
      dimensional (2D) islands at 300 K, with the transition to 3D particle growth at
      0.25 ML (ML=monolayers). Upon heating at 1 K/s, the Pd starts to sinter below 400
      K, and sinters at a nearly constant rate with increasing temperature, covering
      approximately 50% less of the alumina surface by approximately 1000 K, with a
      doubling in particle diameter and an eightfold decrease in particle number
      density. By approximately 1000 K, the number density was approximately 9 x
      10(11)cm(2) for 0.8 ML of Pd, with an average diameter of 5 nm and an average
      thickness of 1 nm.

PMID- 15740402
TI  - Distribution kinetics of polymer crystallization and the Avrami equation.
AB  - Cluster distribution kinetics is adopted to explore the kinetics of polymer
      crystallization. Population balance equations based on crystal size distribution
      and concentration of amorphous polymer segments are solved numerically and the
      related dynamic moment equations are also solved. The model accounts for
      heterogeneous or homogeneous nucleation and crystal growth. Homogeneous
      nucleation rates follow the classical surface-energy nucleation theory. Different
      mass dependences of growth and dissociation rate coefficients are proposed to
      investigate the fundamental features of nucleation and crystal growth. A
      comparison of moment solutions with numerical solutions examines the validity of
      the model. The proposed distribution kinetics model provides a different
      interpretation of the familiar Avrami equation.

PMID- 15740403
TI  - Demixing in athermal mixtures of colloids and excluded-volume polymers from
      density functional theory.
AB  - We study the structure and interfacial properties of model athermal mixtures of
      colloids and excluded volume polymers. The colloid particles are modeled as hard
      spheres whereas the polymer coils are modeled as chains formed from tangentially
      bonded hard spheres. Within the framework of the nonlocal density functional
      theory we study the influence of the chain length on the surface tension and the
      interfacial width. We find that the interfacial tension of the colloid
      interacting polymer mixtures increases with the chain length and is significantly
      smaller than that of the ideal polymers. For certain parameters we find
      oscillations on the colloid-rich parts of the density profiles of both colloids
      and polymers with the oscillation period of the order of the colloid diameter.
      The interfacial width is few colloid diameters wide and also increases with the
      chain length. We find the interfacial width for the end segments to be larger
      than that for the middle segments and this effect is more pronounced for longer
      chains.

PMID- 15740404
TI  - Effect of particle geometry on phase transitions in two-dimensional liquid
      crystals.
AB  - Using a version of density-functional theory which combines Onsager approximation
      and fundamental-measure theory for spatially nonuniform phases, we have studied
      the phase diagram of freely rotating hard rectangles and hard discorectangles. We
      find profound differences in the phase behavior of these models, which can be
      attributed to their different packing properties. Interestingly, bimodal
      orientational distribution functions are found in the nematic phase of hard
      rectangles, which cause a certain degree of biaxial order, albeit metastable with
      respect to spatially ordered phases. This feature is absent in discorectangles,
      which always show unimodal behavior. This result may be relevant in the light of
      recent experimental results which have confirmed the existence of biaxial phases.
      We expect that some perturbation of the particle shapes (either a certain degree
      of polydispersity or even bimodal dispersity in the aspect ratios) may actually
      destabilize spatially ordered phases thereby stabilizing the biaxial phase.

PMID- 15740405
TI  - On the difference in scattering behavior of cyclic and linear polymers in bulk.
AB  - It has been suggested that, due to topological constraints, rings in the melt may
      assume a more compact shape than Gaussian chains. In this paper, we exploit the
      availability of narrow fractions of perdeuterated linear and cyclic
      polydimethylsiloxane (PDMS) and, through the analysis of the small angle neutron
      scattering (SANS) profiles, demonstrate the difference in scattering properties
      of linear and cyclic PDMS molecules. As expected for Gaussian chains, for the H/D
      linear PDMS samples, log-log plots of the scattered intensity versus scattering
      vector Q display a Q((-2)) dependence. However, for H/D cyclic blends, the
      scaling exponent is higher than 2, as predicted by computer simulations reported
      in the literature. We show that cyclic molecules in bulk display the
      characteristic maximum in plots of scattered intensity versus Q((-2)) that is
      expected on the basis of Monte Carlo calculations and from the Casassa equation
      [E. F. Casassa, J. Polym. Sci. A 3, 605 (1965)]. It is also shown that, for
      rings, the Debye equation [P. Debye, J. Appl. Phys. 15, 338 (1944)] is no longer
      appropriate to describe the SANS profiles of H/D cyclic blends, at least up to
      M(w) approximately 10 000. For these samples, the Casassa form factor gives a
      better representation of the SANS data and we show that this function which was
      developed for monodisperse cyclics is still adequate to describe our slightly
      polydisperse samples. Deviations from all above observations are noted for
      M(w)>11 000 and are attributed to partial contamination of cyclic samples with
      linear chains. The failure of both the Debye and the Casassa form factors could
      be due to contamination of the cyclic fractions by linear polymers or to a real
      conformational change.

PMID- 15740406
TI  - Evaluating changes of writhe in computer simulations of supercoiled DNA.
AB  - We compute changes in the writhe of a polygonal space curve when one of the
      vertices is displaced. The resulting expressions can be used in simulations of
      supercoiled DNA. For Brownian dynamics simulations, the expressions can be used
      to eliminate the explicit twisting degree of freedom. For Monte Carlo
      simulations, they can be used in fast local moves. Preliminary Monte Carlo
      simulations using only such fast local moves show that these can be used to
      efficiently simulate small DNA supercoils.

PMID- 15740407
TI  - Quantum-mechanical studies of NMR properties of solutes in liquid crystals: a new
      strategy to determine orientational order parameters.
AB  - We present a quantum-mechanical method to calculate the tensorial NMR magnetic
      properties of molecules in liquid crystals. The method exploits a density
      functional description for the solute and the integral equation formalism version
      of the polarizable continuum model to include the effects of the dielectric
      anisotropy of the solvent on the wave function of the solute molecule and on its
      response to an applied magnetic field. Taking into account the dependence of the
      calculated molecular tensors on the solute orientation, we have derived the
      necessary expressions to relate such tensors to the spectral observables. These
      equations are then used to determine order parameters by calculating the nuclear
      shieldings of various solutes in the nematic ZLI-1167. Comparisons with
      experimental data of the same parameters are finally presented.

PMID- 15740408
TI  - Configurational temperatures and interactions in charge-stabilized colloid.
AB  - A system's temperature can be expressed in terms of its constituents'
      instantaneous positions rather than their momenta. Such configurational
      temperature definitions offer substantial benefits for experimental studies of
      soft condensed matter systems, most notably their applicability to overdamped
      systems whose instantaneous momenta may not be accessible. We demonstrate that
      the configurational temperature formalism can be derived from the classical
      hypervirial theorem, and introduce a hierarchy of hyperconfigurational
      temperature definitions, which are particularly well suited for experimental
      studies. We then use these analytical tools to probe the electrostatic
      interactions in monolayers of charge-stabilized colloidal spheres confined by
      parallel glass surfaces. The configurational and hyperconfigurational
      temperatures, together with a thermodynamic sum rule, provide previously lacking
      self-consistency tests for interaction measurements based on digital video
      microscopy, and thereby cast light on controversial reports of confinement
      induced like-charge attractions. We further introduce a method to determine
      unknown parameters in a model potential by using consistency of the
      configurational and hyperconfigurational temperatures as a set of constraints.
      This approach, in principle, also should provide the basis for a model-free
      estimation of the pair potential.

PMID- 15740411
TI  - The Global HIV/AIDS Vaccine Enterprise: scientific strategic plan.

PMID- 15740412
TI  - A shot in the arm for AIDS vaccine research.

PMID- 15740413
TI  - Scaling up AIDS treatment: what is the potential impact and what are the risks?

PMID- 15740414
TI  - Are current theories of panic falsifiable?
AB  - The authors examine 6 theories of panic attacks as to whether empirical
      approaches are capable of falsifying them and their heuristic value. The authors
      conclude that the catastrophic cognitions theory is least falsifiable because of
      the elusive nature of thoughts but that it has greatly stimulated research and
      therapy. The vicious circle theory is falsifiable only if the frightening
      internal sensations are specified. The 3-alarms theory postulates an
      indeterminate classification of attacks. Hyperventilation theory has been
      falsified. The suffocation false alarm theory lacks biological parameters that
      unambiguously index dyspnea or its distinction between anticipatory and panic
      anxiety. Some correspondences postulated between clinical phenomena and brain
      areas by the neuroanatomical hypothesis may be falsifiable if panic does not
      depend on specific thoughts. All these theories have heuristic value, and their
      unfalsifiable aspects are capable of modification.

PMID- 15740415
TI  - Blood, breath, fears redux, and panic attacks: comment on Roth, Wilhelm, and
      Pettit (2005).
AB  - This article discusses the hyperventilation theory (HVT) of panic attacks (PAs)
      proposed by R. Ley in the context of criticisms raised by W. T. Roth, F. H.
      Wilhelm, and D. Pettit. Their interpretation of HVT is flawed by
      misunderstanding, misinterpretation, and oversimplification of the complex
      psychophysiological principles on which current HVT is based. Consequently, the
      "propositions" they derive are inappropriate. Further, Roth et al.
      disregarded/overlooked: (a) differences among types of PAs, (b) abundant
      empirical evidence that PA patients are distinguished by presence or absence of
      prominent respiratory symptoms (e.g., overbreathing), and (c) Ley's (1992b)
      classification of PAs based on 10 psychophysiological distinctions. The review by
      Roth et al. falls short of standards required to falsify HVT. Current HVT of PAs
      is tenable and testable.

PMID- 15740417
TI  - Why does social exclusion hurt? The relationship between social and physical
      pain.
AB  - The authors forward the hypothesis that social exclusion is experienced as
      painful because reactions to rejection are mediated by aspects of the physical
      pain system. The authors begin by presenting the theory that overlap between
      social and physical pain was an evolutionary development to aid social animals in
      responding to threats to inclusion. The authors then review evidence showing that
      humans demonstrate convergence between the 2 types of pain in thought, emotion,
      and behavior, and demonstrate, primarily through nonhuman animal research, that
      social and physical pain share common physiological mechanisms. Finally, the
      authors explore the implications of social pain theory for rejection-elicited
      aggression and physical pain disorders.

PMID- 15740418
TI  - Why does separation distress hurt? Comment on MacDonald and Leary (2005).
AB  - Evidence is substantial that separation-distress circuitry in animal models is
      related intimately to opioid-sensitive pain regulatory systems of the brain. The
      evidence that basic pain-affect mechanisms are integral to the feelings of
      defensive fear anxiety and aggression is modest. Although anger and anxiety can
      be reduced by opiates, the effects are not as robust and specific as those
      observed with the low doses that quell separation distress. The role of "social
      pain" may be larger for the affective underpinnings of jealousy, shame, and guilt
      (all variants of social exclusion and abandonment) than for fear and aggression.
      Interdisciplinary insights might be facilitated by more forthright analyses of
      how affective states are created within the brain. This will require better
      dialogue between behavioral neuroscientists and the rest of psychology interested
      in foundational psychoevolutionary issues.

PMID- 15740419
TI  - Social exclusion and the hierarchical defense system: comment on MacDonald and
      Leary (2005).
AB  - G. MacDonald and M. R. Leary hypothesized that physical pain and social exclusion
      share many affective features in common. In this comment, the author discusses
      the implications of J. A. Gray and N. McNaughton's (2000) hierarchical defense
      system model, which MacDonald and Leary used in the development of their
      theoretical claims. Issues are discussed that require, at least, clarification;
      but more substantive problems need closer consideration of hierarchically
      organized defense. It is argued that research findings may be better understood
      (a) by systems of interacting neural modules, which lead to state dissociations
      between affective states, and (b) by general modulatory influences on the entire
      defense system that lead to trait associations (i.e., personality) between
      physical pain and emotional distress.

PMID- 15740421
TI  - The construct of work commitment: testing an integrative framework.
AB  - This study meta-analytically examined extensive literature associated with work
      commitment. The primary purposes were to (a) cumulate correlations among
      dimensions of work commitment to see which were intercorrelated and (b) determine
      impact of work commitment dimensions and subdimensions on specific outcome
      variables (job satisfaction, job performance, turnover intentions, and turnover).
      Results were cumulated across 997 articles. The positive manifold of correlations
      suggests the presence of a common psychological construct underlying different
      commitment forms, with the exception of calculative, continuance, and union
      commitment. Most of the 94 meta-analyzed correlations were small, suggesting that
      concept redundancy is not a major concern. Meta-analyses of the correlations of
      24 commitment constructs with 4 outcome variables suggest that different
      commitment forms have similar patterns of correlations with outcome variables.

PMID- 15740422
TI  - Anger, anxiety, and depression as risk factors for cardiovascular disease: the
      problems and implications of overlapping affective dispositions.
AB  - Several recent reviews have identified 3 affective dispositions--depression,
      anxiety, and anger-hostility--as putative risk factors for coronary heart
      disease. There are, however, mixed and negative results. Following a critical
      summary of epidemiological findings, the present article discusses the construct
      and measurement overlap among the 3 negative affects. Recognition of the overlap
      necessitates the development of more complex affect-disease models and has
      implications for the interpretation of prior studies, statistical analyses,
      prevention, and intervention in health psychology and behavioral medicine. The
      overlap among the 3 negative dispositions also leaves open the possibility that a
      general disposition toward negative affectivity may be more important for disease
      risk than any specific negative affect.

PMID- 15740423
TI  - Adoption and cognitive development: a meta-analytic comparison of adopted and
      nonadopted children's IQ and school performance.
AB  - This meta-analysis of 62 studies (N=17,767 adopted children) examined whether the
      cognitive development of adopted children differed from that of (a) children who
      remained in institutional care or in the birth family and (b) their current
      (environmental) nonadopted siblings or peers. Adopted children scored higher on
      IQ tests than their nonadopted siblings or peers who stayed behind, and their
      school performance was better. Adopted children did not differ from their
      nonadopted environmental peers or siblings in IQ, but their school performance
      and language abilities lagged behind, and more adopted children developed
      learning problems. Taken together, the meta-analyses document the positive impact
      of adoption on the children's cognitive development and their remarkably normal
      cognitive competence but delayed school performance.

PMID- 15740424
TI  - Avoidance of relatively aggressive male Japanese Quail (Coturnix japonica) by
      sexually experienced conspecific females.
AB  - Sexually experienced female Japanese quail (Coturnix japonica) that are offered a
      choice between 2 conspecific males previously observed engaging in an aggressive
      encounter prefer to affiliate with the less aggressive male. The authors
      determined whether this apparent preference for less aggressive males results
      from females approaching less aggressive individuals or avoiding more aggressive
      individuals. The authors found that females that had seen 2 males fight before
      choosing, in counterbalanced order, between each of them and a neutral stimulus
      were indifferent to less aggressive males but avoided more aggressive males. The
      results are consistent with the view that in species in which male courtship and
      mating are potentially harmful to females, females keep away from relatively
      aggressive males in order to avoid the physical punishment that can result from
      contact with them.

PMID- 15740425
TI  - Differences between golden hamsters (Mesocricetus auratus) and Norway rats
      (Rattus norvegicus) in preference for the sole diet that they are eating.
AB  - D. DiBattista (2002) reported that hamsters but not rats showed reduced
      preferences for the sole diet they had eaten for 10 days. In the current study,
      the authors fed Norway rats (Rattus norvegicus) a nutritious diet for either 3 or
      10 days, then tested them either immediately or 1 or 3 days later. The authors
      found that like golden hamsters (Mesocricetus auratus), rats exhibited reduced
      preferences for a prefed diet but only if tested either immediately or 1 day
      after prefeeding, not if tested 3 days later (when D. DiBattista tested his
      hamsters). Rats and hamsters differed in the longevity, not the development, of
      reduced preferences for a palatable food eaten for several consecutive days. Such
      a response might aid dietary generalists in constructing balanced diets when no
      single available food is nutritionally adequate.

PMID- 15740426
TI  - Spatial memory and monitoring of hidden items through spatial displacements by
      chimpanzees (Pan troglodytes).
AB  - This study examined chimpanzee (Pan troglodytes) short-term memory for food
      location in near space. In Experiments 1 and 2, either 1 or 2 items (chocolate
      pieces) were hidden in an array of 3 or 5 containers that either remained
      stationary or were rotated 180 degrees or 360 degrees. When the array remained
      stationary, the chimpanzees remembered both item locations. When arrays were
      rotated, however, chimpanzees found only 1 item. In Experiment 3, 2 items were
      hidden in an array of 7 cups. Both items were found at levels significantly
      better than chance. Ninety percent of errors were made after the 1st item was
      found, and errors reflected memory failure rather than a failure of inhibitory
      control.

PMID- 15740427
TI  - Gorillas (Gorilla gorilla) and orangutans (Pongo pygmaeus) encode relevant
      problem features in a tool-using task.
AB  - Two important elements in problem solving are the abilities to encode relevant
      task features and to combine multiple actions to achieve the goal. The authors
      investigated these 2 elements in a task in which gorillas (Gorilla gorilla) and
      orangutans (Pongo pygmaeus) had to use a tool to retrieve an out-of-reach reward.
      Subjects were able to select tools of an appropriate length to reach the reward
      even when the position of the reward and tools were not simultaneously visible.
      When presented with tools that were too short to retrieve the reward, subjects
      were more likely to refuse to use them than when tools were the appropriate
      length. Subjects were proficient at using tools in sequence to retrieve the
      reward.

PMID- 15740428
TI  - A meta-analysis of primate hand preferences, particularly for reaching.
AB  - P. F. MacNeilage, M. G. Studdert-Kennedy, and B. Lindblom (1987) proposed a
      progression for handedness in primates that was supposed to account for the
      evolution of a right bias in human handedness. To test this proposal, the authors
      performed meta-analyses on 62 studies that provided individual data (representing
      31 species: 9 prosimians, 6 New World monkeys, 10 Old World monkeys, 2 lesser
      apes, and 4 greater apes), of the 118 studies of primate handedness published
      since 1987. Although evidence of a population-level left-handed bias for
      prosimians and Old World monkeys supports P. F. MacNeilage et al., the data from
      apes, New World monkeys, and individual species of prosimians and New World
      monkeys do not. Something other than primate handedness may have been the
      evolutionary precursor of the right bias in hand-use distribution among hominids.

PMID- 15740429
TI  - Androgen mediation of conditioned rhythmic cloacal sphincter movements in
      Japanese Quail (Coturnix japonica).
AB  - Demonstrations of increased reproductive success due to sexual conditioning in
      Japanese quail (Coturnix japonica) have been reported, although the mechanisms
      that underlie these effects have remained elusive. One possible mechanism is
      conditioned rhythmic cloacal sphincter movements (RCSM). Two experiments were
      conducted with male quail to determine whether associations between a conditioned
      stimulus (CS) and a hen would result in the ability of the CS to elicit RCSM, and
      to explore the androgen mediation of conditioned RCSM. The results suggest that a
      focal CS paired with visual access to a female will elicit RCSM via a
      representation of the hen activated by the CS. Further, the available evidence
      indicates that conditioned RCSM is androgen mediated and that this learning may
      transfer across breeding seasons.

PMID- 15740430
TI  - Agonistic onset marks emotional changes and dispersal propensity in wild house
      mouse males (Mus domesticus).
AB  - The authors investigated implications of agonistic onset for anxiety and
      dispersive motivation in maturing wild house mouse males (Mus domesticus).
      Laboratory-kept fraternal pairs either developed agonistic dominance or stayed
      amicable during their first 2 months of life, when the authors assessed open
      field behavior and dispersal propensity. State anxiety was lower in amicable than
      agonistic males and higher in subordinate than dominant ones. During subsequent
      dispersal trials, 1 dominant and 1 amicable male from 2 fraternal pairs were
      concomitantly introduced into seminatural enclosures containing 3 females. One
      male invariably became territorial. The defeated males, if previously dominant,
      dispersed at significantly higher rates than if previously amicable. The authors
      conclude that agonistic onset during development represents an adaptive
      behavioral switch from a submissive-philopatric to agonistic-dispersive coping
      strategy.

PMID- 15740431
TI  - Agonistic screams in wild chimpanzees (Pan troglodytes schweinfurthii) vary as a
      function of social role.
AB  - Some nonhuman primates have demonstrated the capacity to communicate about
      external objects or events, suggesting primate vocalizations can function as
      referential signals. However, there is little convincing evidence for
      functionally referential communication in any great ape species. Here, the
      authors demonstrate that wild chimpanzees (Pan troglodytes schweinfurthii) of
      Budongo forest, Uganda, give acoustically distinct screams during agonistic
      interactions depending on the role they play in a conflict. The authors analyzed
      the acoustic structure of screams of 14 individuals, in the role of both
      aggressor and victim. The authors found consistent differences in the acoustic
      structure of the screams, across individuals, depending on the social role the
      individual played during the conflict. The authors propose that these 2 distinct
      scream variants, produced by victims and aggressors during agonistic
      interactions, may be promising candidates for functioning as referential signals.

PMID- 15740432
TI  - Inhibitory control and response selection in problem solving: how cotton-top
      tamarins (Saguinus oedipus) overcome a bias for selecting the larger quantity of
      food.
AB  - When presented with a choice between 1 and 3 pieces of food in a type of reversed
      contingency task, 4 cotton-top tamarins (Saguinus oedipus) consistently chose the
      3 pieces of food and received nothing, even though the choice of 1 piece would
      have yielded 3. However, in a task in which the tamarins received the 1 piece of
      food when they chose it, all subjects learned to select 1 over 3. Thus, the
      tamarins' prior failure on the reversed contingency task did not result entirely
      from an inherent inability to suppress the prepotent response of reaching to the
      larger of 2 quantities of food. After the experience of selecting the smaller
      quantity and receiving it, all of the tamarins solved the version of the reversed
      contingency task that they failed initially. These results suggest that the
      tamarins' initial failure may have reflected a difficulty with selecting an
      alternative response option.

PMID- 15740433
TI  - Auditory categorization of complex sounds by rats (Rattus norvegicus).
AB  - Little research has explored the auditory categorization abilities of mammals. To
      better understand these processes, the authors tested the abilities of rats
      (Rattus norvegicus) to categorize multidimensional acoustic stimuli by using a
      classic category-learning task developed by R. N. Shepard, C. I. Hovland, and H.
      M. Jenkins (1961). Rats proved to be able to categorize 8 complex sounds on the
      basis of either the direction or rate of frequency modulation but not on the
      basis of the range of frequency modulation. Rats' categorization abilities were
      limited but improved slowly and incrementally, suggesting that learning was not
      facilitated by selective attention to acoustic dimensions.

PMID- 15740434
TI  - Personality traits in dumpling squid (Euprymna tasmanica): context-specific
      traits and their correlation with biological characteristics.
AB  - Personality traits are a major class of behavioral variation often observed
      within populations of animals. However, little is known of the integration
      between personality and an individual's underlying biology. To address this, the
      authors measured personality traits in squid (Euprymna tasmanica) in 2 contexts
      while also describing trait correlates with biological parameters. Four traits
      (shy avoidance- bold aggression, activity, bury persistence, and reactivity) were
      reliably measured; however, trait expression between contexts was not correlated
      and thus was context-specific. Trait variation was not a function of gender or of
      somatic or reproductive condition but was explained partially by a squid's sexual
      maturity and its size. Results are discussed in terms of the interplay between
      personality variation and resulting life history strategies in animals.

PMID- 15740435
TI  - A new model for sexual conditioning: the ring dove (Streptopelia risoria).
AB  - Sexual conditioning investigations have primarily used rats and domestic quail as
      subjects. Although much has been learned from such experiments, the relative
      simplicity of rat and quail reproductive behavior prohibits investigation of
      certain experimental questions about sexual conditioning. In contrast, the
      reproductive behavior of male and female ring doves (Streptopelia risoria) is
      complex, involving courtship, bonding, and parental care. In the present
      experiment, male ring doves that were presented with a visual conditioned
      stimulus paired with access to their pair-bonded mate (the unconditioned
      stimulus) showed sexual conditioned responding in the presence of the conditioned
      stimulus. These results represent the first evidence of sexual conditioning in
      ring doves and illustrate the potential of ring doves as a useful model for
      future sexual conditioning investigations.

PMID- 15740436
TI  - The effect of human command phonetic characteristics on auditory cognition in
      dogs (Canis familiaris).
AB  - Six dogs (Canis familiaris) were trained to sit and come reliably in response to
      tape-recorded commands. The phonemes within these commands were then changed, and
      the dogs' behavior in response to these modified commands was recorded.
      Performance markedly declined in all cases, with the type of alteration affecting
      response to the modified sit command but not to the modified come command. The
      results suggest that dogs do not perceive a tape-recorded command as simply a
      physical sound but that they recognize a relationship between certain sounds.

PMID- 15740437
TI  - An online measure of thought suppression.
AB  - An online thought-suppression paradigm was developed to test predictions of
      ironic process theory. Participants concentrated on or suppressed a particular
      semantic category. Semantic activation was indexed by the latency to name words
      from the category. In Experiments 1 and 2, an analog intrusion was introduced
      while participants were trying to suppress the information. Results consistent
      with ironic process theory were observed using words with polar opposites in
      Experiment 1 and words without polar opposites in Experiment 2. To determine
      whether these effects were dependent on the analog intrusion, Experiment 3
      replicated Experiment 1 without the intrusion. Concentration generated semantic
      activation, but suppression exacerbated this activation. The data imply that
      hyperaccessibility results from efforts to suppress, whereas the processes of
      thought suppression identified by ironic process theory require the presence of
      material inconsistent with a desired cognitive state.

PMID- 15740438
TI  - We can do it: the interplay of construal orientation and social comparisons under
      threat.
AB  - The authors investigated how a collective self-construal orientation in
      combination with positive social comparisons "turns off" the negative effects of
      stereotype threat. Specifically, Experiment 1 demonstrated that stereotype threat
      led to increased accessibility of participants' collective self ("we").
      Experiment 2 showed that this feeling of "we-ness" in the stereotype threat
      condition centered on the participants' stereotyped group membership and not on
      other important social groups (e.g., students). Experiment 3 indicated that in
      threat situations, when participants' collective self is accessible, positive
      social comparison information led to improved math test performance and less
      concern, whereas in nonthreat situations, when the collective self is less
      accessible, positive comparison information led to worse test performance and
      more concern. Our final experiment revealed that under stereotype threat, only
      those comparison targets who are competent in the relevant domain (math), rather
      than in domains unrelated to math (athletics), enhanced participants' math test
      performance.

PMID- 15740439
TI  - American = White?
AB  - Six studies investigated the extent to which American ethnic groups (African,
      Asian, and White) are associated with the category "American." Although strong
      explicit commitments to egalitarian principles were expressed in Study 1, Studies
      2-6 consistently revealed that both African and Asian Americans as groups are
      less associated with the national category "American" than are White Americans.
      Under some circumstances, a dissociation between mean levels of explicit beliefs
      and implicit responses emerged such that an ethnic minority was explicitly
      regarded to be more American than were White Americans, but implicit measures
      showed the reverse pattern (Studies 3 and 4). In addition, Asian American
      participants themselves showed the American = White effect, although African
      Americans did not (Study 5). The American = White association was positively
      correlated with the strength of national identity in White Americans. Together,
      these studies provide evidence that to be American is implicitly synonymous with
      being White.

PMID- 15740440
TI  - Categorizing others: the dynamics of person construal.
AB  - A fundamental question in social cognition is whether people categorize others on
      the basis of the social groups to which they belong. Integrating ideas from
      related work on face processing, the current research explored the emergence and
      boundary conditions of person categorization. Using speeded responses to facial
      stimuli as a marker of category activation, the authors showed in 3 experiments
      that person categorization: (a) occurs only under active-encoding conditions and
      (b) does not extend to applicable but task-irrelevant categorical dimensions, but
      (c) is sensitive to overlap in the perceptual features that support multiple
      categorical construals. The authors consider the implications of these findings
      for models of social-cognitive functioning and the component processes that
      support person perception.

PMID- 15740441
TI  - To know you is to love you: the implications of global adoration and specific
      accuracy for marital relationships.
AB  - Despite the strong positive feelings that characterize newlyweds, many marriages
      end in disappointment. To understand this shift, the authors argue that although
      newlyweds' global relationship evaluations may be uniformly positive, not all
      spouses base their global adoration on an accurate perception of their partner's
      specific qualities. Two longitudinal studies confirmed that whereas most
      newlyweds enhanced their partners at the level of their global perceptions,
      spouses varied significantly in their perceptions of their partners' specific
      qualities. For wives, but not for husbands, more accurate specific perceptions
      were associated with their supportive behaviors, feelings of control in the
      marriage, and whether or not the marriage ended in divorce. Thus, love grounded
      in specific accuracy appears to be stronger than love absent accuracy.

PMID- 15740442
TI  - Exposure to benevolent sexism and complementary gender stereotypes: consequences
      for specific and diffuse forms of system justification.
AB  - Many have suggested that complementary gender stereotypes of men as agentic (but
      not communal) and women as communal (but not agentic) serve to increase system
      justification, but direct experimental support has been lacking. The authors
      exposed people to specific types of gender-related beliefs and subsequently asked
      them to complete measures of gender-specific or diffuse system justification. In
      Studies 1 and 2, activating (a) communal or complementary (communal + agentic)
      gender stereotypes or (b) benevolent or complementary (benevolent + hostile)
      sexist items increased support for the status quo among women. In Study 3,
      activating stereotypes of men as agentic also increased system justification
      among men and women, but only when women's characteristics were associated with
      higher status. Results suggest that complementary stereotypes psychologically
      offset the one-sided advantage of any single group and contribute to an image of
      society in which everyone benefits through a balanced dispersion of benefits.

PMID- 15740443
TI  - Perceptions of conflict and support in romantic relationships: the role of
      attachment anxiety.
AB  - Guided by attachment theory, a 2-part study was conducted to test how perceptions
      of relationship-based conflict and support are associated with relationship
      satisfaction/closeness and future quality. Dating partners completed diaries for
      14 days (Part 1) and then were videotaped while discussing a major problem that
      occurred during the diary study (Part 2). Part 1 reveals that more anxiously
      attached individuals perceived more conflict with their dating partners and
      reported a tendency for conflicts to escalate in severity. Perceptions of daily
      relationship-based conflicts negatively impacted the perceived
      satisfaction/closeness and relationship futures of highly anxious individuals,
      whereas perceptions of greater daily support had positive effects. Part 2 reveals
      that highly anxious individuals appeared more distressed and escalated the
      severity of conflicts (rated by observers) and reported feeling more distressed.
      The authors discuss the unique features of attachment anxiety and how changing
      perceptions of relationship satisfaction/closeness and stability could erode
      commitment over time.

PMID- 15740444
TI  - Prosocial emotions and helping: the moderating role of group membership.
AB  - In this article, the authors introduce and test a group-level perspective on the
      role of empathy and interpersonal attraction in helping. In line with our
      predictions, Study 1, a longitudinal field study of 166 AIDS volunteers,
      confirmed that empathy was a stronger predictor of helping when the recipient of
      assistance was an in-group member than when that person was an out-group member.
      Also as hypothesized, attraction was a stronger predictor of helping when the
      recipient was an out-group member than when that person was an in-group member.
      Study 2 replicated and further extended these results in a laboratory experiment
      on spontaneous helping of a person with hepatitis. Strengthening the validity of
      the findings, in both studies the effects of empathy and attraction held up even
      when the authors statistically controlled for potential alternative predictors of
      helping. The theoretical and practical implications of these findings for helping
      in intergroup contexts are discussed.

PMID- 15740445
TI  - Universal features of personality traits from the observer's perspective: data
      from 50 cultures.
AB  - To test hypotheses about the universality of personality traits, college students
      in 50 cultures identified an adult or college-aged man or woman whom they knew
      well and rated the 11,985 targets using the 3rd-person version of the Revised NEO
      Personality Inventory. Factor analyses within cultures showed that the normative
      American self-report structure was clearly replicated in most cultures and was
      recognizable in all. Sex differences replicated earlier self-report results, with
      the most pronounced differences in Western cultures. Cross-sectional age
      differences for 3 factors followed the pattern identified in self-reports, with
      moderate rates of change during college age and slower changes after age 40. With
      a few exceptions, these data support the hypothesis that features of personality
      traits are common to all human groups.

PMID- 15740446
TI  - Personality, family history, and competence in early adult romantic
      relationships.
AB  - The present investigation tested how well family characteristics and the
      personality traits assessed by the Multidimensional Personality Questionnaire (A.
      Tellegen, 1982) measured in late adolescence predict aspects of romantic
      relationships in early adulthood. Nurturant-involved parenting practices and
      personality traits were related to observed negative interactions and to couples'
      reports of relationship quality. These results from a prospective longitudinal
      study suggest that the origins of competence in romantic relationships can be
      found both in individual differences in personality (especially in negative
      emotionality) and in differences in developmental experiences. Discussion further
      develops an account of relationship success and dysfunction that integrates
      proximal factors, such as couple interactions, with more distal factors such as
      personality and socialization experiences.

PMID- 15740447
TI  - The rhetoric and reality of gap closing: when the "have-nots" gain but the
      "haves" gain even more .
AB  - Many forms of intervention, across different domains, have the surprising effect
      of widening preexisting gaps between disadvantaged youth and their advantaged
      counterparts--if such interventions are made available to all students, not just
      to the disadvantaged. Whether this widening of gaps is incongruent with American
      interests and values requires an awareness of this gap-widening potential when
      interventions are universalized and a national policy that addresses the
      psychological, political, economic, and moral dimensions of elevating the top
      students--tomorrow's business and science leaders--and/or elevating the bottom
      students to redress past inequalities and reduce the future costs associated with
      them. This article is a first step in bringing this dilemma to the attention of
      scholars and policymakers and prodding a national discussion.

PMID- 15740448
TI  - The staircase to terrorism: a psychological exploration.
AB  - To foster a more in-depth understanding of the psychological processes leading to
      terrorism, the author conceptualizes the terrorist act as the final step on a
      narrowing staircase. Although the vast majority of people, even when feeling
      deprived and unfairly treated, remain on the ground floor, some individuals climb
      up and are eventually recruited into terrorist organizations. These individuals
      believe they have no effective voice in society, are encouraged by leaders to
      displace aggression onto out-groups, and become socialized to see terrorist
      organizations as legitimate and out-group members as evil. The current policy of
      focusing on individuals already at the top of the staircase brings only short
      term gains. The best long-term policy against terrorism is prevention, which is
      made possible by nourishing contextualized democracy on the ground floor.

PMID- 15740449
TI  - Inference by eye: confidence intervals and how to read pictures of data.
AB  - Wider use in psychology of confidence intervals (CIs), especially as error bars
      in figures, is a desirable development. However, psychologists seldom use CIs and
      may not understand them well. The authors discuss the interpretation of figures
      with error bars and analyze the relationship between CIs and statistical
      significance testing. They propose 7 rules of eye to guide the inferential use of
      figures with error bars. These include general principles: Seek bars that relate
      directly to effects of interest, be sensitive to experimental design, and
      interpret the intervals. They also include guidelines for inferential
      interpretation of the overlap of CIs on independent group means. Wider use of
      interval estimation in psychology has the potential to improve research
      communication substantially.

PMID- 15740450
TI  - Imaging race.
AB  - Researchers have recently begun to use the tools of neuroscience to examine the
      social psychological responses associated with race. This article serves as a
      review of the developing literature in this area. It advances the argument that
      neuroscience studies of race have the potential to shape fundamental assumptions
      about race, and the interplay between social and biological processes more
      generally.

PMID- 15740451
TI  - Leo Joseph Postman (1918-2004).

PMID- 15740452
TI  - Donald B. Lindsley (1907-2003).

PMID- 15740453
TI  - John W. Atkinson (1923-2003).

PMID- 15740457
TI  - Opposite changes in carotid versus aortic stiffness during healthy human
      pregnancy.
AB  - Systemic arterial compliance has been known to increase during healthy pregnancy,
      whereas, recently, the carotid artery has been reported to stiffen. To clarify
      this controversy, we simultaneously measured aortic PWV (pulse wave velocity) and
      carotid artery elastic parameters in a cohort of pregnant women. Twelve
      normotensive pregnant women were studied longitudinally during the three
      trimesters of pregnancy (T1, T2 and T3 respectively) and 12 weeks PP
      (postpartum). Carotid artery diastolic diameter and pulsatile distension was
      measured by an echo-wall tracking method and carotid pulse pressure by
      applanation tonometry. Carotid strain, compliance, distensibility coefficient,
      stiffness index beta, Einc (incremental elastic modulus) and augmentation index
      were calculated. Aortic PWV was determined to estimate aortic distensibility. All
      carotid artery elastic parameters indicated significant stiffening from T1 to T3
      (1.8+/-0.2 versus 2.9+/-0.3 mmHg for Einc), which was reversed after delivery
      (2.3+/-0.2 mmHg). Aortic PWV decreased during pregnancy (6.2+/-0.2 versus 5.4+/
      0.2 m/s) and increased in the PP period (6.7+/-0.2 m/s). No correlation was found
      between changes in carotid artery elastic parameters and changes in aortic PWV
      either from T1 to T3 or from T3 to PP. The carotid artery exhibits regionally
      specific stiffening during pregnancy, which appears to represent a qualitatively
      different change in arterial elastic behaviour.

PMID- 15740456
TI  - Pulse wave analysis during supine rest may identify subjects with recurrent
      vasovagal syncope.
AB  - In the present study, we studied whether analysis of the FAP (finger arterial
      pressure) waveform during supine rest discriminates subjects with recurrent VVS
      (vasovagal syncope) from healthy controls. Signal-averaged FAP waveforms
      (Finapres) were obtained in 32 head-up tilt-test-positive subjects with recurrent
      VVS (35 +/- 13 years) and in 32 sex- and age-matched healthy controls. The DT
      (time delay) between the systolic and diastolic peaks of the FAP waveform was
      measured and large artery SI (stiffness index) was calculated as a ratio of body
      height and DT. VVS patients had significantly shorter DT compared with controls
      (303 +/- 31 compared with 329 +/- 18 ms; P < 0.001) and higher SI (5.79 +/- 0.70
      compared with 5.20 +/- 0.36 m/s; P < 0.001). The differences were independent of
      heart rate and blood pressure. SI > 5.45 m/s identified subjects with syncope
      with a sensitivity of 72% and a specificity of 84%. Age-corrected DT (cDT = DT +
      age-350) identified subjects with syncope with a sensitivity of 75% and a
      specificity of 84%. Combined use of cDT <0 ms and SI > 5.45 m/s increased
      sensitivity and specificity to 81% and 96% respectively. The discriminative power
      of FAP descriptors improved further when younger subjects were excluded. In
      subjects aged >30 years (median age), the combination of cDT and SI identified
      subjects with syncope with a sensitivity of 93% and a specificity of 100%. These
      results suggest that FAP descriptors during supine rest might be useful in the
      diagnosis of VVS in middle-aged subjects.

PMID- 15740458
TI  - Biodistribution, plasma kinetics and quantification of single-pass pulmonary
      clearance of adrenomedullin.
AB  - The biodistribution, pharmacokinetics and multi-organ clearance of the
      vasodilator peptide AM (adrenomedullin) were evaluated in rats and its single
      pass pulmonary clearance was measured in dogs by the indicator-dilution
      technique. Intravenously administered 125I-rAM(1-50) [rat AM(1-50)] was rapidly
      cleared following a two-compartment model with a very rapid distribution half
      life of 2.0 min [95% CI (confidence interval), 1.98-2.01] and an elimination half
      life of 15.9 min (95% CI, 15.0-16.9). The lungs retained most of the injected
      activity with evidence of single-pass clearance, since retention was lower after
      intra-arterial (13.5+/-0.6%) compared with intravenous (30.4+/-1.5%; P < 0.001)
      injection. Lung tissue levels of total endogenous AM were 20-fold higher than in
      other organs with no difference in plasma levels across the pulmonary
      circulation. In dogs, there was 36.4+/-2.1% first-pass unidirectional extraction
      of 125I-rAM(1-50) by the lungs that was reduced to 21.9+/-2.4% after the
      administration of unlabelled rAM(1-50) (P < 0.01). Extraction was not affected by
      calcitonin-gene-related peptide administration (40.6+/-2.9%), but was slightly
      reduced by the C-terminal fragment of human AM(22-52) (31.4+/-3.3%; P < 0.01).
      These data demonstrate that the lungs are a primary site for AM clearance in vivo
      with approx. 36% first-pass extraction through specific receptors. This suggests
      that the lungs not only modulate circulating levels of this peptide, but also
      represent its primary target.

PMID- 15740459
TI  - Plasma vascular endothelial growth factor as a marker for early vascular damage
      in hypertension.
AB  - Elevation of plasma VEGF (vascular endothelial growth factor) has been noted in
      patients with hypertension or atherosclerosis. VEGF has been regarded as a marker
      for endothelial dysfunction. However, the role of VEGF in hypertension-induced
      vascular injury and its relationship with endothelial function have not been
      studied. This study included 20 untreated hypertensive men with grade 1 or 2
      hypertensive retinopathy, 10 untreated hypertensive men without hypertensive
      retinopathy and 10 healthy controls. None of the hypertensive patients had
      diabetes, renal impairment or overt vascular diseases. Plasma VEGF and adhesion
      molecules were measured using ELISAs. Endothelial function was measured by FMD
      (flow-mediated vasodilation) of the brachial artery. Plasma levels of VEGF,
      excluding adhesion molecules, were significantly higher in hypertensive patients
      with retinopathy when compared with patients without retinopathy (152.4+/-80.8
      pg/ml versus 104.7+/-27.2 pg/ml, P = 0.035) or controls (152.4+/-80.8 pg/ml
      versus 98.9+/-23.7 pg/ml, P = 0.025). Levels of FMD were significantly lower in
      hypertensive patients than controls, but there were no significant differences
      between patients with or without retinopathy. Degrees of FMD were inversely
      correlated with VEGF levels (r = -0.351, P = 0.031). Elevation of plasma VEGF was
      associated with hypertensive retinopathy. Plasma VEGF could be used as a marker
      of early vascular damage induced by hypertension.

PMID- 15740461
TI  - Overcoming treatment resistance in obsessive-compulsive disorder.

PMID- 15740460
TI  - Oxidation of hypotaurine and cysteine sulphinic acid by peroxynitrite.
AB  - Peroxynitrite mediates the oxidation of the sulphinic group of both HTAU
      (hypotaurine) and CSA (cysteine sulphinic acid), producing the respective
      sulphonates, TAU (taurine) and CA (cysteic acid). The reaction is associated with
      extensive oxygen uptake, suggesting that HTAU and CSA are oxidized by the one
      electron transfer mechanism to sulphonyl radicals, which may initiate an oxygen
      dependent radical chain reaction with the sulphonates as final products. Besides
      the one-electron mechanism, HTAU and CSA can be oxidized by the two-electron
      pathway, leading directly to sulphonate formation without oxygen consumption. The
      apparent second-order rate constants for the direct reaction of peroxynitrite
      with HTAU and CSA at pH 7.4 and 25 degrees C are 77.4+/-5 and 76.4+/-9 M(-1).s(
      1) respectively. For both sulphinates, the apparent second-order rate constants
      increase sharply with decrease in pH, and the sigmoidal curves obtained are
      consistent with peroxynitrous acid as the species responsible for sulphinate
      oxidation. The kinetic data, together with changes in oxygen uptake, sulphinate
      depletion, sulphonate production, and product distribution of nitrite and
      nitrate, suggest that oxidation of sulphinates by peroxynitrite may take place by
      the two reaction pathways whose relative importance depends on reagent
      concentrations and pH value. In the presence of bicarbonate, the direct reaction
      of sulphinates with peroxynitrite is inhibited and the oxidative reaction
      probably involves only the radicals *NO2 and CO3*-, generated by decomposition of
      the peroxynitrite-CO2 adduct.

PMID- 15740462
TI  - Obsessive-compulsive disorder: a critical review of therapeutic perspectives.
AB  - OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic disabling disease
      with profound implications for social functioning. Thirty per cent of all
      patients with OCD show insufficient improvement with state-of-the-art treatment.
      Conventional treatment and alternative treatment options for this population were
      investigated. METHOD: A selective review of the relevant scientific literature on
      OCD treatment and treatment resistance was conducted. RESULTS: In addition to
      serotonin reuptake inhibitors (SRIs) and cognitive-behavioural therapy,
      alternative monotherapies, SRI augmentation strategies with a variety of drugs
      and electroconvulsive therapy have shown results in individual cases, but no
      conclusive evidence has been found in placebo-controlled trials. While studies
      investigating neurosurgery for refractory OCD show positive results, most of
      these studies have methodological shortcomings. CONCLUSION: Novel approaches
      currently under investigation that have shown promising effects for treatment
      resistant OCD include SRI augmentation with atypical antipsychotics and chronic
      deep brain stimulation, a new surgical technique. Placebo-controlled trials for
      both treatment options will be needed to confirm preliminary findings.

PMID- 15740463
TI  - A review of self-management interventions for panic disorders, phobias and
      obsessive-compulsive disorders.
AB  - OBJECTIVE: To review current evidence for the clinical and cost-effectiveness of
      self-management interventions for panic disorder, phobias and obsessive
      compulsive disorder (OCD). METHOD: Papers were identified through computerized
      searches of databases for the years between 1995 and 2003, manual searches and
      personal contacts. Only randomized-controlled trials were reviewed. RESULTS: Ten
      studies were identified (one OCD, five panic disorder, four phobias). Effective
      self-management interventions included cognitive-behavioural therapy (CBT) and
      exposure to the trigger stimuli for phobias and panic disorders. All involved
      homework. There was evidence of effectiveness in terms of improved symptoms and
      psychological wellbeing when compared with standard care, waiting list or
      relaxation. Brief interventions and computer-based interventions were effective
      for most participants. In terms of quality, studies were mainly based on small
      samples, lacked long-term follow-up, and failed to address cost-effectiveness.
      CONCLUSION: Despite the limitations of reviewed studies, there appears to be
      sufficient evidence to warrant greater exploration of self-management in these
      disorders.

PMID- 15740464
TI  - Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a
      controlled forensic database study of 14,857 suicides.
AB  - OBJECTIVE: To test the hypothesis that selective serotonin reuptake inhibitor
      (SSRI) antidepressants may have a suicide emergent effect, particularly in
      children and adolescents. METHOD: Detections of different antidepressants in the
      forensic toxicological screening of 14 857 suicides were compared with those in
      26,422 cases of deaths by accident or natural causes in Sweden 1992-2000.
      RESULTS: There were 3411 detections of antidepressants in the suicides and 1538
      in the controls. SSRIs had lower odds ratios than the other antidepressants. In
      the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group,
      SSRIs had lower relative risk in suicides compared with non-SSRIs. CONCLUSION:
      The hypothesis that treatment of depressed individuals with SSRIs leads to an
      increased risk of suicide was not supported by this analysis of the total
      suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9
      years, either in adults or in children or adolescents.

PMID- 15740465
TI  - Trauma exposure and post-traumatic stress disorder in the general population.
AB  - OBJECTIVE: To examine the lifetime prevalence of trauma experiences and post
      traumatic stress disorder (PTSD). METHOD: Questionnaire-assessed PTSD, the type
      of traumatic event experienced, perceived trauma impact, and trauma frequency in
      1824 randomly selected men and women. RESULTS: PTSD lifetime prevalence was
      estimated at 5.6% with a 1 : 2 male-to-female ratio, in spite of men reporting
      greater trauma exposure. The highest PTSD risk was associated with sexual and
      physical assault, robbery and multiple trauma experiences. Controlling for trauma
      type did not account for gender differences, while controlling for experienced
      distress did. CONCLUSION: The conditional probability for PTSD varied as a
      function of trauma type, frequency and impact of the event, with increased rates
      associated with prevalent trauma exposure and higher perceived distress. The
      latter accounted for the gender effect, suggesting that gender differences in
      PTSD in part represent a generally greater vulnerability to stress in women.

PMID- 15740466
TI  - Mental disorders, disability and health service use amongst Vietnamese refugees
      and the host Australian population.
AB  - OBJECTIVE: To compare the prevalence of common mental disorders, disability and
      health service utilization amongst Vietnamese refugees resettled in Australia for
      11 years, with data obtained from a national survey of the host population.
      METHOD: A stratified multistage probability household survey of 1611 Vietnamese
      undertaken in the state of New South Wales was compared with data from 7961
      Australian-born respondents. Measures included the CIDI 2.1 and the MOS SF-12.
      RESULTS: The 12-month prevalence of anxiety, depression and drug and alcohol
      dependence amongst Vietnamese was 6.1% compared with 16.7% amongst Australians.
      Vietnamese with a mental illness reported higher disability but exhibited similar
      levels of mental health consultation. The overall service burden of mental
      disorders was lower for the Vietnamese. CONCLUSION: The findings suggest that
      refugee groups resettled for some time in Western countries may show sound mental
      health adaptation and do not necessarily impose a burden on general or mental
      health services.

PMID- 15740467
TI  - Risk factors associated with migraine or chronic daily headache in out-patients
      with major depressive disorder.
AB  - OBJECTIVE: This study investigated independent comorbidities and factors
      associated with migraine and chronic daily headache (CDH) in out-patients with
      major depressive disorder (MDD). METHOD: Consecutive psychiatric out-patients
      fulfilling the DSM-IV criteria of MDD were enrolled. Headaches were diagnosed
      based on the criteria proposed by the second edition of the International
      Classification of the Headache Disorders. Psychiatric comorbidities were checked
      using the Mini International Neuropsychiatric Interview. Scores of the Hamilton
      Depression Rating Scale (HAMD) and duration of major depressive episodes (MDE)
      were evaluated. Multivariate logistic regression was used to decide risk factors.
      RESULTS: One hundred and fifty-one patients (34 men and 117 women) participated
      in the study, among which 73 (48.3%) reported a history of migraine and 32
      (21.2%) reported CDH during this MDE. Higher HAMD scores, female gender, and
      chronic depression were independently associated with migraine or CDH.
      CONCLUSION: For MDD patients with a higher depressive severity and longer
      duration of MDE, especially female gender, surveillance of migraine and CDH might
      be indicated.

PMID- 15740468
TI  - The psychiatrist's image in commercially available American movies.
AB  - OBJECTIVE: To explore quantitatively how American movies portray
      psychiatrists/therapist. METHOD: A total of 106 movies were reviewed regarding
      how psychiatrists/therapists were portrayed. The psychiatrist's or therapist's
      sex, age, clinical competence and knowledge, boundary violations, attitude toward
      the patient, influence in the movie's events, treatment modality or modalities
      used, intervention's outcome, and therapeutic setting. RESULTS: The
      psychiatrists/therapists tended to be males (71.2%), and (regardless of sex)
      middle-aged (50.8%). Despite the general view of the psychiatrists/therapists as
      friendly (63.6%), there was an over-representation of boundary violations. The
      percentage of total boundary violations was 44.9% of the cases portrayed and
      sexual violations accounted for 23.7%, while non-sexual violations accounted for
      30.5% (with 9.3% overlap). The appearance of clinical incompetence was 47.5%.
      CONCLUSION: The image of psychiatrists/therapists in commercially available
      movies is not flattering: close to one out of two violated boundaries, close to
      one out of four committed a sexual boundary violation, and the
      psychiatrist/therapist was as likely to be incompetent as competent. The bright
      point is that psychiatrists/therapists were depicted as more likely to be
      friendly.

PMID- 15740469
TI  - Depression and chronic obstructive pulmonary disease (COPD). Impact on survival.
AB  - OBJECTIVE: To determine if the presence of depression in patients suffering from
      chronic obstructive pulmonary disease (COPD) would have an independent impact on
      mortality. METHOD: Prospective evaluation of the impact of depression according
      to the ICD-10 criteria for depression. Cox proportional hazards regression was
      used to evaluate the independent impact of depression after controlling for
      significant univariate clinical predictors in the data set. Consenting out
      patients (n = 49) who meet the criteria for COPD between September 1997 and
      September 1998. There were no age limits (range: 53-90 years). The sample was 67%
      female. Survival status at follow-up after a mean of 803 days was measured.
      RESULTS: At follow-up, 16 patients had died. Depression significantly reduced the
      mortality risk at follow-up (hazard ratio, 0.30; 95% confidence interval, 0.10
      0.93; P = 0.037). The impact of depression remained after control for forced
      expiratory volume during the first second (FEV1), the only multivariate
      significant predictor of mortality in the data set (hazard ratio, 0.27; 95%
      confidence interval, 0.09-0.84; P = 0.024). CONCLUSION: Depression in out
      patients suffering from COPD appears to be an independent protector for
      mortality. Additional studies in larger samples are needed to replicate this
      finding and to determine possible underlying pathogenetic mechanisms.

PMID- 15740470
TI  - Deep venous thrombosis and pulmonary embolism following physical restraint.
AB  - OBJECTIVE: We describe a case of deep venous thrombosis (DVT) and pulmonary
      embolism (PE) following the use of physical restraint in a patient with a
      diagnosis of acute delusional psychotic disorder. METHOD: A new case report of
      DVT and PE associated with prolonged physical restraint is presented. The
      literature on physical restraint, DVT, and PE was reviewed using a search of
      Medline and Psychinfo from 1966 to the present. RESULTS: Four other reported
      cases of DVT and PE were found in association with physically restrained
      patients. CONCLUSION: Risk of DVT and PE in association with immobilization
      during physical restraint may occur in spite of no pre-existing risk factors.
      Medical guidelines for the prevention of thrombosis following physical restraint
      are presented. Despite the absence of controlled trials of treatment
      effectiveness, the catastrophic outcome of DVT and PE warrants early and vigorous
      intervention in patients undergoing physical restraint.

PMID- 15740472
TI  - Biography of K. O'Connor.

PMID- 15740473
TI  - Hydatid disease of the liver.

PMID- 15740474
TI  - Stress and the gastrointestinal tract.
AB  - Stress, defined as an acute threat to homeostasis, evokes an adaptive or
      allostatic response and can have both a short- and long-term influence on the
      function of the gastrointestinal tract. The enteric nervous system is connected
      bidirectionally to the brain by parasympathetic and sympathetic pathways forming
      the brain-gut axis. The neural network of the brain, which generates the stress
      response, is called the central stress circuitry and includes the paraventricular
      nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input
      from the somatic and visceral afferent pathways and also from the visceral motor
      cortex including the medial prefrontal, anterior cingulate and insular cortex.
      The output of this central stress circuit is called the emotional motor system
      and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and
      pain modulatory systems. Severe or long-term stress can induce long-term
      alteration in the stress response (plasticity). Corticotropin releasing factor
      (CRF) is a key mediator of the central stress response. Two CRF receptor
      subtypes, R1 and R2, have been described. They mediate increased colonic motor
      activity and slowed gastric emptying, respectively, in response to stress.
      Specific CRF receptor antagonists injected into the 0 block these visceral
      manifestations of stress. Circulating glucocorticoids exert an inhibitory effect
      on the stress response by receptors located in the medial prefrontal cortex and
      hippocampus. Many other neurotransmitters and neuroimmunomodulators are being
      evaluated. Stress increases the intestinal permeability to large antigenic
      molecules. It can lead to mast cell activation, degranulation and colonic mucin
      depletion. A reversal of small bowel water and electrolyte absorption occurs in
      response to stress and is mediated cholinergically. Stress also leads to
      increased susceptibility to colonic inflammation, which can be adaptively
      transferred among rats by sensitized CD4(+) lymphocytes. The association between
      stress and various gastrointestinal diseases, including functional bowel
      disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal
      reflux disease, is being actively investigated. Attention to the close relation
      between the brain and gut has opened many therapeutic avenues for the future.

PMID- 15740475
TI  - Antibacterial and antimycobacterial treatment for inflammatory bowel disease.
AB  - A variety of medicines have been used for the treatment of inflammatory bowel
      disease. Antibacterial therapy has demonstrated promise by both improving
      symptoms and causing disease remission. The mechanism is unknown, but may be
      related to either eliminating a key pathogen, decreasing the number of bacterial
      secretory products or defective particles, a direct immunomodulating effect, or
      reducing secondary bacterial invasion. Historically, a large number of bacterial
      species have been suspected as being major contributors to the etiology of
      inflammatory bowel disease, including ulcerative colitis and Crohn's disease.
      Many trials of antibacterial agents have been carried out in inflammatory bowel
      disease. Recently, treatments have focused on Gram-negative anaerobes and
      mycobacteria. The present paper briefly reviews antimicrobial and
      antimycobacterial treatments in inflammatory bowel disease.

PMID- 15740476
TI  - Classification of hydatid liver cysts.
AB  - A number of investigations advocate various classification systems for liver
      hydatid cysts. However, none permits predicting the treatment outcome or making
      clinical decisions regarding medical treatment; open surgery; punction,
      aspiration, injection, reaspiration (PAIR); or laparoscopy. An international
      hydatid disease registry employing an uniform nomenclature and consistent
      reporting methods would allow more rational comparison of different management
      strategies. TN(R)C (topography, nature, recurrent, complication) classification
      is a comprehensive system based on four criteria: location (T), natural history
      (N), recurrence (R) and complications (C) of the cyst. This pictorial review
      illustrates the classification and puts accent of its clinical usefulness. The
      TN(R)C classification provides a standardized description formula of every liver
      hydatid cyst, permitting multiple comparisons and analyses.

PMID- 15740477
TI  - Bird's-eye view on gastric cancer research of the past 25 years.
AB  - This paper provides a bird's-eye view of our 25-year research work on gastric
      cancer, including both exploration of pathogenesis and preclinical or clinical
      applications of diagnosis and treatment. Although there have been achievements
      and reasons for applause, there are, nonetheless, more failings and teachings.
      Some problems that we experienced 25 years ago are still problems we have to face
      today. We are absolutely not singing the same old tune. Looking back makes us
      wiser and our way smoother. Although it is a long and arduous way to further
      study gastric cancer, we are willing to devote ourselves to it.

PMID- 15740478
TI  - Clinical course of ulcerative colitis in patients with and without primary
      sclerosing cholangitis.
AB  - BACKGROUND AND AIM: We noticed in our practice that patients with ulcerative
      colitis (UC) who have developed primary sclerosing cholangitis (PSC) experience a
      milder course of colonic disease. Our objective in this study was to define
      whether or not there is any difference between UC activity and its course in
      patients with and without PSC. METHODS: Nineteen patients with UC and PSC (eight
      male, mean age 25 years) were enrolled. To every patient with UC and PSC, three
      patients with UC alone (total of 57 patients, 28 male, mean age 24 years) matched
      for age at onset, duration of the disease and extension of colonic disease were
      selected as the control group. We used number of hospitalizations due to activity
      of UC and number of short corticosteroid administrations in various years of
      follow-up as variables indicating course and severity of the colonic disease in
      this period. For comparing trends of UC activity between two groups, we used
      repeated measures two-way analysis of variances. RESULTS: Mean duration of follow
      up in case and control groups was 12.2 +/- 5.7 and 11.4 +/- 4.9 years,
      respectively. Two groups had no significant difference in use of sulfasalzine or
      aminosalicylates. Number of hospitalizations and courses of steroid therapy
      because of UC activity decreased significantly over time (P < 0.000) in both
      groups, and it was significantly higher in controls than in cases (P = 0.045 and
      0.032, respectively). CONCLUSIONS: Development of PSC in patients with UC might
      have a positive effect on colonic disease. Further investigations to evaluate the
      basis of this improvement are warranted.

PMID- 15740479
TI  - Altered phenotype of dextran sulfate sodium colitis in interferon regulatory
      factor-1 knock-out mice.
AB  - BACKGROUND AND AIMS: Interferon regulatory factor-1 (IRF-1) is a transcription
      factor with antiviral, proinflammatory and tumor suppressor properties. We
      examined the role of IRF-1 in dextran sulfate sodium colitis, a murine model of
      inflammatory bowel disease, to determine if absence of the gene would protect
      against colitis. METHODS: C57BL/6J mice with a targeted disruption of IRF-1 and
      wild-type C57BL/6J controls received five 7-day cycles of 2% dextran sulfate
      sodium alternating with five 7-day cycles of water. Colonic tissue was formalin
      fixed for histological analysis and total RNA extracted for gene chip and SYBR
      green real-time polymerase chain reaction (PCR) analysis. RESULTS: Histological
      analysis revealed increased distortion of crypt architecture in the dextran
      sulfate sodium-treated, IRF-1 -/- animals as compared to dextran sulfate sodium
      treated wild-type animals. Five of 15 dextran sulfate sodium-treated IRF-1 -/-
      mice, but only one of 14 dextran sulfate sodium-treated wild-type mice, developed
      colonic dysplasia. Microarray analysis comparing colonic gene expression in IRF-1
      -/- and wild-type animals revealed decreased expression of caspases, genes
      involved in antigen presentation, and tumor suppressor genes in the IRF-1 -/-
      animals. Increased expression of genes involved in carcinogenesis and
      immunoglobulin and complement genes was also noted in the knock-out animals.
      CONCLUSIONS: Absence of IRF-1 is not protective in dextran sulfate sodium
      colitis.

PMID- 15740480
TI  - Post-infectious irritable bowel syndrome in patients with Shigella infection.
AB  - BACKGROUND AND AIMS: Bacterial gastroenteritis has been known as a risk factor of
      irritable bowel syndrome (IBS). Several risk factors of post-infectious IBS (PI
      IBS) have been documented. The aims of this study were to verify the role of
      bacterial gastroenteritis in the development of IBS and the risk factors for the
      development of PI-IBS. The clinical course of PI-IBS was also investigated.
      METHODS: We recruited 143 patients with shigellosis during its outbreak and 113
      controls. Both groups were followed up for 12 months. Bowel symptoms were
      evaluated by use of questionnaires at 3, 6 and 12 months after the initial
      recruitment. RESULTS: Complete data were obtained from 101 patients (70.6%) and
      102 healthy controls (90.3%). At 12 months, 15 patients and six controls had IBS
      (adjusted OR; 2.9, 95% CI; 1.1-7.9). Of the 15 patients, five had IBS symptoms
      consistently for 12 months, three did not have IBS symptoms initially and seven
      had fluctuating bowel symptoms. The duration of diarrhea was an independent risk
      factor of PI-IBS. CONCLUSIONS: Bacterial gastroenteritis is a risk factor of IBS
      and the duration of diarrhea as the index of severity of initial illness is an
      independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over
      the 1 year of follow-up.

PMID- 15740481
TI  - Effects of enhanced viscosity on canine gastric and intestinal motility.
AB  - BACKGROUND AND AIM: The aim of this study was to investigate the effect of
      enhanced viscosity on gastric emptying and gastrointestinal motor and
      myoelectrical activities in dogs. METHOD: The study was performed in eight
      healthy female hound dogs chronically implanted with four pairs of gastric and
      two pairs of intestinal serosal electrodes and a duodenal fistula. Each dog was
      studied in three sessions and fed with three test meals with different viscosity.
      Gastric emptying was monitored for 2 h simultaneously with gastric and intestinal
      myoelectrical recordings. RESULTS: The liquid test meal containing either 0.78%
      or 1.21% of galactomannan significantly delayed gastric emptying but had no
      effect on postprandial blood glucose levels in comparison with the meal
      containing no galactomannan. The liquid test meal containing either 0.78% or
      1.21% of galactomannan significantly increased the frequency and strength of
      intestinal motility but had no effect on intestinal slow wave rhythms. The
      product with enhanced viscosity had no effect on gastric motor activity or
      gastric slow waves. CONCLUSION: It was concluded that enhanced viscosity delays
      gastric emptying, increases postprandial intestinal but not gastric motility, and
      has no effects on gastric or intestinal slow waves.

PMID- 15740482
TI  - Short-term recurrent abdominal pain related to Helicobacter pylori infection in
      children.
AB  - BACKGROUND AND AIM: The causal relationship between Helicobacter pylori infection
      and recurrent abdominal pain in children is still under debate. This study
      assessed the relationship between H. pylori infection and recurrent abdominal
      pain (RAP) in preschool and school children. METHODS: A total of 1271 preschool
      and school children completed a questionnaire to define the RAP or short-term RAP
      (SRAP) with pain duration from 2 weeks to 3 months. The serum samples of 118
      children with RAP, 60 with SRAP and 212 control children without abdominal pain
      were all tested for anti-H. pylori IgG. Children with abdominal pain and anti-H.
      pylori seropositivity were followed for 1 year to assess the relationship of H.
      pylori infection and recurrent abdominal pain. RESULTS: The prevalence rates of
      RAP and SRAP in children were 9.8% (124/1271) and 5.5% (70/1271), respectively.
      Children with SRAP had a higher anti-H. pylori seropositive rate than those with
      RAP (25%vs 5%, P < 0.001) and control (25%vs 9%, P = 0.001). Among children with
      SRAP, the epigastric pain was related to H. pylori infection (P = 0.002). One
      year later, 71% (15/21) of the follow-up children (15 with SRAP, six with RAP)
      became symptom free regardless of the persistence of H. pylori. CONCLUSION: H.
      pylori infection is more commonly found in children with short-term RAP, and
      presentation of epigastric pain in these cases can be considered as a warning
      alarm to screen for H. pylori infection.

PMID- 15740483
TI  - Helicobacter pylori reinfection rate 3 years after successful eradication.
AB  - BACKGROUND AND AIM: Helicobacter pylori (HP) infection is one of the most
      prevalent human infections and has been implicated as a predisposing factor in
      gastric cancer, chronic active gastritis, duodenal ulcer, gastric ulcer and
      gastric lymphoma. Reinfection after successful eradication is quite uncommon in
      adults. In the only study carried out in Iran, a reinfection rate of 19.1% after
      1 year has been reported. We studied the rate of reinfection 3 years after
      successful HP eradication. METHODS: All patients who had undergone HP eradication
      3 years before the study and had successful eradication verified by a negative
      (14)C urea breath test (UBT) 1 year after eradication were invited to complete a
      questionnaire and undergo another UBT. In addition, spouses and the offspring of
      those testing positive were offered an UBT. RESULTS: Ninety-eight patients were
      enrolled (49% male). Mean age was 44 +/- 13 years (range: 18-75 years). Twenty
      patients (20.4%) had a positive UBT. Epigastric burning (25%vs 69%) and pyrosis
      (50%vs 67%) were seen less commonly in those who were HP free at 3 years compared
      to those who tested positive for HP. CONCLUSIONS: According to our data, in our
      region the HP reinfection rate is 20.4% 3 years after successful eradication.

PMID- 15740484
TI  - Functional promotor polymorphism in RANTES gene does not influence the clinical
      course of Helicobacter pylori infection.
AB  - BACKGROUND AND AIMS: Helicobacter pylori was found to increase the transcription
      of RANTES as a potent chemoattractant cytokine in mucosal inflammation. The aim
      of this study was to test if a functional promotor polymorphism in the RANTES
      gene leading to a higher transcriptional activity influences the severity of the
      mucosal damage in H. pylori infected individuals. METHODS: A single nucleotide
      polymorphism, C-471T, was genotyped by TaqMan technology in a sample of 344
      consecutive patients with H. pylori infection undergoing upper gastrointestinal
      endoscopy and 370 blood donors. Association with the development of erosions and
      stomach or duodenum ulcers as well as atrophic gastritis were tested. RESULTS:
      None of the genotypes were associated with the severity of mucosal damage in
      stomach or duodenum (P > 0.05). CONCLUSION: Even though H. pylori itself induces
      expression of RANTES, at the transcriptional level, genetic variations leading to
      higher transcriptional activity do not modify the degree of inflammation.

PMID- 15740485
TI  - Gastric tone variations during gastric infusion of fiber-supplemented formulas.
AB  - BACKGROUND AND AIM: Despite gastric feeding being a common method of artificial
      nutritional support, little is known about the effects of enteral nutrition on
      fundic motor function. The objective of this study was to assess variations of
      fundic tone and their relation to antroduodenal motility before, during and after
      nasogastric feeding supplemented or not with fibers. METHOD: Double-blinded
      studies were performed in random order with the three different diets (2100 kJ)
      in eight volunteers: fiber free (FF), insoluble fiber (IF) or mixed fiber (MF).
      Fundic tone was recorded by barostat concomitantly with antroduodenal manometry.
      RESULTS: Before the infusion, seven spontaneous fundic relaxations occurred
      during the 24 studies. Concomitantly or less than 2 min before these relaxations,
      phase III of the migrating motor complex (MMC) with a duodenal onset was
      recorded. Only the 17 studies without spontaneous fundic relaxation (4 FF, 6 MF,
      7 IF) were suitable for the assessment of fundic response to infusion.
      Disappearance of the volume waves at the beginning and during the whole infusion
      was observed in 11/17 studies (FF 50%, MF 66% and IF 71%, NS), but a proximal
      gastric relaxation following the beginning of the infusion occurred in only three
      individuals, one with the FF and two with IF. When it occurred, fundic relaxation
      was observed within 2 min and was not different from those observed
      spontaneously. CONCLUSION: Gastric infusion of a polymeric diet, supplemented or
      not with fiber, did not promote fundic relaxation in most of the cases but often
      induced a disappearance of gastric volume waves.

PMID- 15740486
TI  - Pilot study to assess patient outcomes following endoscopic application of
      photodynamic therapy for advanced cholangiocarcinoma.
AB  - BACKGROUND: Photodynamic therapy (PDT) has demonstrated promise in the palliative
      treatment of advanced cholangiocarcinoma. The aim of this pilot study was to
      assess the outcome in patients with non-resectable cholangiocarcinoma following
      endoscopic application of PDT directly into the biliary tract. METHODS: In
      patients with advanced cholangiocarcinoma, endoscopic retrograde
      cholangiopancreatography (ERCP) was performed to define the proximal and distal
      extent of intraductal tumor. Sodium porfimer was administered intravenously to
      all patients. Forty-eight hours later, a commercially available cylindrical
      diffusing laser fiber (1-2.5 cm in length, OptiGuide) designed for esophageal use
      was advanced across the biliary strictures. Laser light was applied at a power of
      400 mW/cm fiber for a total energy of 180 J/cm(2) using an argon-pumped tunable
      dye laser. Patients received endoscopic PDT every 3 months provided they
      maintained a favorable performance status. Plastic biliary stents were replaced
      immediately following light application and were maintained in all patients.
      RESULTS: Using a preloaded catheter, adequate positioning of the laser fiber was
      achieved in all patients. Eight patients with advanced cholangiocarcinoma
      received a total of 19 PDT treatments, range 1-5 treatments/patient. All eight
      patients were followed until death; mean follow-up was 9.8 months. Median
      survival from the date of the first PDT treatment was 276 days, which compares
      favorably with published series that have reported median survival times between
      45 and 127 days for patients with bismuth type III and IV tumors treated with
      stenting alone. CONCLUSIONS: Endoscopic application of PDT demonstrates promise
      in prolonging survival in patients with advanced cholangiocarcinoma. Additional
      randomized clinical trials using commercially available fibers are needed to
      fully evaluate both the optimum frequency and treatment interval of endoscopic
      PDT in the management of advanced cholangiocarcinoma.

PMID- 15740487
TI  - Dual treatment of albendazole in hepatic hydatidosis: New therapeutic modality in
      52 cases.
AB  - BACKGROUND: Hepatic hydatidosis still remains as a serious problem in general
      surgery. Recurrence and/or secondary hydatidosis rates are up to 25% in the cases
      treated with surgery alone. Albendazole is the most commonly used drug in the
      medical treatment of echinococcosis. The aim of the present study was to evaluate
      the effect of albendazole using the intraoperative and perioperative periods as
      dual therapy. METHODS: Fifty-two cases of hepatic hydatidosis were evaluated and
      treated by dual treatment of albendazole together with surgery. Perioperative
      albendazole treatment was given in a dose of 12-15 mg/kg per day in four divided
      doses. The treatment started 2-28 days before the surgery when the diagnosis was
      established and continued for 2-24 months (4.76 +/- 3.25) postoperatively in a
      cyclic monthly form. A total of 1.7 microg/mL albendazole solution was used as a
      protoscolicidal agent in the cystic cavity intraoperatively. In the postoperative
      period serology, ultrasonography and computed tomography evaluations were done.
      The follow-up period was 5-92 months (mean: 62.48 months). RESULTS: There was no
      recurrence in the present study. One patient died in the 6th postoperative week
      due to cerebral hydatidosis and multiple organ failure. Early and late morbidity
      rates were 7.69 and 9.61%, respectively. CONCLUSIONS: Dual albendazole treatment
      is effective in the prevention of recurrences and/or secondary hydatidosis.

PMID- 15740488
TI  - Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic
      hepatitis B.
AB  - BACKGROUND: Severe acute exacerbations of chronic hepatitis B virus (HBV)
      infection can spontaneously occur and rapidly progress to fatal hepatic failure.
      The purpose of the present paper was to identify factors that could influence the
      rapid progression of liver disease to hepatic failure, and assess the effects of
      lamivudine on serious disease. METHODS: Twenty-five patients with spontaneous
      severe acute exacerbation (accompanied by jaundice and coagulopathy) were
      consecutively treated with lamivudine. Their clinical outcomes were compared with
      those of 25 lamivudine-untreated patients, as historical controls. RESULTS: Six
      lamivudine-treated patients (24%)and seven controls (28%) rapidly developed
      hepatic failure. Lamivudine monotherapy did not significantly prevent progression
      to hepatic failure. Multivariate analysis identified baseline serum bilirubin
      >/=6 mg/dL (odds ratio [OR]: 5.61; 95% confidence interval [CI]: 1.66-21.61; P =
      0.018), pre-existing cirrhosis (OR: 4.52; 95%CI: 1.26-30.42; P = 0.034), and
      baseline prothrombin time <40% (OR: 3.75; 95%CI: 1.03-43.86; P = 0.045) as
      independent determinants of the event. Of the aforementioned patients with
      hepatic failure, three lamivudine-treated patients (50%) and two controls (29%)
      survived (P > 0.15). However, lamivudine induced a sustained normalization of
      liver function and inhibited the development of cirrhosis in survivors.
      CONCLUSIONS: Lamivudine monotherapy conferred no significant protection against
      rapid progression of the disease to hepatic failure, but it resulted in long-term
      benefits. Lamivudine combined with other drugs could be more beneficial for
      patients with the aforementioned risk factors.

PMID- 15740489
TI  - Factors associated with response to lamivudine: Retrospective study in a tertiary
      care clinic serving patients with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is an important cause of end stage
      liver disease and hepatocellular carcinoma. Controlled clinical trials indicate
      treatment with lamivudine results in positive clinical responses. The study goal
      was to determine if the response to lamivudine treatment (HBeAg loss, HBV DNA
      loss and alanine aminotransferase [ALT] reduction) differs according to
      pretherapy (pre-tx) ALT levels. METHODS: This was a retrospective review of
      medical record data. All CHB patients at all stages of disease (including
      cirrhotic) with more than two visits to the clinic were included in the study (n
      = 719). Kaplan-Meier survival and Cox proportional hazards were estimated.
      RESULTS: Of the total 719 HBsAg (+) patients, 317 were treated with lamivudine
      150 mg or 100 mg daily. Among HBeAg positive patients, at 3 years, Kaplan-Meier
      estimates of the loss of HBeAg were 40%, 57% and 61% for pre-tx ALT < upper limit
      of normal (ULN), 1-2 x ULN and >2 x ULN, respectively. Similar results of HBV-DNA
      loss were seen in HBeAg negative patients. CONCLUSIONS: In this setting, we
      observed that pre-tx ALT levels were not associated with response to lamivudine,
      but that lower platelet count and female sex in HBeAg (+) patients were important
      predictive factors of a favorable response to lamivudine therapy.

PMID- 15740490
TI  - Comparative study of genotype B and C hepatitis B virus-induced chronic hepatitis
      in relation to the basic core promoter and precore mutations.
AB  - BACKGROUND: The clinicopathological profiles and outcome of chronic hepatitis B
      can differ by hepatitis B virus (HBV) genotypes. In Japan, genotype B and C are
      two major HBV genotypes. The basic core promoter and precore mutations are other
      known viral factors for disease activity, although the relationship between HBV
      genotypes and these mutations is not fully understood. METHODS: The HBV genotypes
      in 90 patients with chronic hepatitis B were determined using an ELISA. Obtained
      data were correlated with clinicopathological parameters, basic core promoter,
      precore and the nucleotide 1858 mutations of the HBV genome. RESULTS: Among 90
      cases, 20 (22.2%) had genotype B and 70 (77.8%) had genotype C HBV. Genotype B
      patients were older than genotype C patients (44.0 +/- 13.9 vs 34.7 +/- 11.0 P =
      0.0022). The HBeAg was more prevalent in genotype C than B patients (P = 0.0008)
      while anti-HBe was more common in genotype B than C patients (P = 0.0002). Serum
      aspartate aspartate aminotransferase/alanine aminotransferase levels (B: 220.7 +/
      612.8/257.0 +/- 498.0 IU/L vs C: 111.3 +/- 122.8/201.6 +/- 229.4 IU/L, P =
      0.16/0.48) and HBV viral loads in blood (B: 6.1 +/- 3.1 log genome equivalent
      [LGE]/mL vs C: 6.7 +/- 2.3 LGE/mL, P = 0.42) were equivalent. The seroconversion
      from HBeAg to anti-HBe occurred significantly earlier in genotype B than C
      patients (62 +/- 53 months vs 136 +/- 54 months, P = 0.0028) during the mean
      observation period of 149 +/- 82 months even under various therapeutic
      modalities. The categories III and IV of the histological activity index in
      genotype C were higher (III: P < 0.005, IV: P < 0.05, n = 68) than that in B
      patients whereas category II was higher in genotype B than C patients (P < 0.05).
      The double mutation (1762T/1764A) in the basic core promoter was more frequently
      found in genotype C than in B HBV (P = 0.0068), whereas the precore mutation
      (1896A) was more common in genotype B than C HBV (P = 0.0233). The incidence of
      1858C that was complementary to the precore mutation site in the stem-loop
      structure in, was equally rare in both genotype B and C HBV. CONCLUSIONS:
      Genotype B patients were older, had earlier HBeAg seroconversion and exhibited
      more severe lobular necroinflammation, less portal inflammation and fibrosis than
      genotype C patients. This genotypic difference is related to the basic core
      promoter and precore mutations irrespective of 1858C. (c) 2004 Blackwell
      Publishing Asia Pty Ltd.

PMID- 15740491
TI  - Evidence against a role for endotoxin in the hepatic encephalopathy of rats with
      thioacetamide-induced fulminant hepatic failure.
AB  - BACKGROUND AND AIMS: Endotoxin has been proposed to participate in the
      development of hepatic encephalopathy. However, there is no published data
      concerning the effects of endotoxin neutralization on the degree of hepatic
      encephalopathy. The present study investigated the effect of chronic
      intraperitoneal injection of polymyxin B, a neutralizing antagonist of endotoxin,
      on hepatic encephalopathy in rats with thioacetamide (TAA)-induced fulminant
      hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used.
      Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350
      mg/kg/day) for 3 days. Two series of rats were designed to compare the effects of
      low dose (0.1 mg) or high dose (0.2 mg) intraperitoneal polymyxin B
      administration versus normal saline (NS) on hepatic encephalopathy. The injection
      was twice daily started from 2 days prior to TAA administration and lasted for 5
      days. Severity of encephalopathy was assessed by the counts of motor activity in
      an Opto-Varimex animal activity meter. Plasma levels of endotoxin and tumor
      necrosis factor-alpha (an index of liver injury) were measured by Limulus assay
      and the ELISA method, respectively. RESULTS: Neutralization of endotoxin by
      either low dose or high dose polymyxin B administration did not significantly
      alleviate the degree of hepatic encephalopathy, as represented by the counts of
      motor activities (P > 0.05). Plasma levels of endotoxin and tumor necrosis factor
      alpha were comparable between rats treated with polymyxin B or NS (P > 0.05).
      CONCLUSION: Our findings do not support the notion that endotoxin plays a major
      role in the pathogenesis of hepatic encephalopathy in rats with TAA-induced
      fulminant hepatic failure.

PMID- 15740492
TI  - Human leukocyte antigen haplotypes and HFE mutations in Spanish hereditary
      hemochromatosis and sporadic porphyria cutanea tarda.
AB  - BACKGROUND AND AIMS: It has been postulated that the HFE C282Y mutation (linked
      to human leukocyte antigen [HLA]-A3-B7 haplotype) is not only responsible for
      hereditary hemochromatosis; HLA class I alleles would also contribute to the
      disease pathogenesis. In addition, H63D mutation linked to HLA-A29-B44 would also
      be pathogenetic, particularly in the Mediterranean Basin and throughout the
      world. However, sporadic porphyria cutanea tarda (s-PCT) has also been linked to
      these HFE mutations. In the present work, we have studied HFE mutations and HLA
      genes to test these hypotheses. METHODS: C282Y and H63D mutations together with
      HLA genetic typing have been performed in Spanish hereditary hemochromatosis (n =
      98) and PCT (n = 63) patients. The etiologic fraction (delta) has been used to
      determine the absolute strongest gene linkage to both diseases. RESULTS: The
      Spanish frequent HLA-A29-B44 haplotype is not significantly associated to the
      H63D mutations in hereditary hemochromatosis patients (although it is found more
      frequently in patients than in controls). Sporadic porphyria cutanea tarda
      patients do not show a significant association to H63D mutations, although it is
      also more frequent than in controls; however, compound H63D/C282Y subjects seem
      to bear a significant risk to s-PCT. Allelic C282Y (and not H63D) frequencies
      show a significant association with s-PCT. CONCLUSIONS: The postulated additional
      risk of hereditary hemochromatosis given by class I HLA antigens may be secondary
      to the HFE gene linkage disequilibrium with certain class I alleles or to the
      existence of other neighboring genetic pathogenetic factors in our Spanish
      sample.

PMID- 15740493
TI  - Fate of bradykinin on the rat liver when administered by the venous or arterial
      route.
AB  - BACKGROUND AND AIM: Bradykinin (BK) infused into the portal vein elicits a
      hypertensive response via the B2 receptor (B2R) and is efficiently hydrolyzed by
      the liver. Our purpose was to characterize the mechanism of interaction between
      BK and the liver. METHOD: BK, HOE-140 (a B2R antagonist), des-R(9)-BK (a B1R
      agonist) and enzyme inhibitors were used in monovascular or bivascular perfusions
      and in isolated liver cell assays. RESULTS: Des-R(9)-BK did not elicit a portal
      hypertensive response (PHR); BK infused into the hepatic artery elicited a
      calcium-dependent PHR and a calcium-independent arterial hypertensive response
      (HAHR), with the latter being almost abolished by naproxen. BK has a predominant
      distribution in the extracellular space and an average hepatic extraction of 8%
      in the steady state. Hydrolysis products of infused BK (R(1)-F(5) and R(1)-P(7))
      did not elicit PHR. Angiotensin converting enzyme (ACE) is concentrated in the
      perivenous region and B2R in the periportal region. Microphysiometry showed that
      BK (and not a B1 agonist) interacts with stellate cells and the endothelial
      sinusoidal/Kupffer cell fraction. This effect was inhibited by the B2R
      antagonist. CONCLUSIONS: Events can be summarized as: the hypertensive action of
      BK on sinusoidal cells of the periportal region is followed by its hydrolysis by
      ACE which is primarily present in the perivenous region; there is no functional
      B1R in the normal liver; BK induces HAHR via eicosanoid release and PHR by a
      distinct pathway on the B2R. Our data suggest that BK may participate in the
      modulation of sinusoidal microvasculature tonus both in the portal and the
      arterial routes.

PMID- 15740494
TI  - Differences in long-term survival after transjugular intrahepatic portosystemic
      shunt for refractory ascites and variceal bleed.
AB  - OBJECTIVE: To compare the survival after transjugular intrahepatic portosystemic
      shunt (TIPS) for refractory ascites and variceal bleed, and to identify the
      factors predictive of survival. METHODS: Single tertiary center, retrospective
      prospective study. Chart review was performed on all patients who underwent TIPS
      between 1993 and 2000 and prospective follow-up to determine survival. Pre- and
      post-TIPS clinical parameters were compared and Kaplan-Meier analysis was applied
      to compare the survival of both groups. Cox regression was used to identify
      predictors of survival after TIPS. RESULTS: A total of 163 patients were
      included, 62 with refractory ascites and 101 with variceal bleed. Both groups had
      similar age (48.2 vs 48.9 year; P = 0.65) and consisted of predominantly
      Caucasians (51%) and Mexican-Americans (39%). More than 75% had chronic hepatitis
      C, alcoholic liver disease or both. Overall, the median survival was
      significantly better for variceal bleed (2 years) compared with refractory
      ascites (6 months) (P < 0.001). This survival advantage persisted in patients
      with Mayo risk score greater than 1.17. Transjugular intrahepatic portosystemic
      shunt improved severe ascites in 45% of patients (P = 0.03). Mayo risk score was
      highly predictive of survival after TIPS with a hazard ratio of 2.3, followed by
      Child-Pugh score, creatinine, albumin and ethnicity, with better survival among
      Mexican-Americans. Shunt dysfunction (31%) and hepatic encephalopathy (27%) were
      the most common complications of TIPS. CONCLUSIONS: Patients who received TIPS
      for variceal bleed had significantly longer survival compared with those for
      refractory ascites. Mexican-Americans had an improved long-term survival compared
      with Caucasians. The reason for this ethnic difference in survival is unclear and
      warrants further prospective evaluation.

PMID- 15740495
TI  - Images of interest. Gastrointestinal: epiploic appendagitis.

PMID- 15740496
TI  - Images of interest. Gastrointestinal: colonic Dieulafoy lesion.

PMID- 15740497
TI  - Images of interest. Gastrointestinal: Abdominal neurofibromatosis.

PMID- 15740498
TI  - Images of interest. Hepatobiliary and pancreatic: Liver histopathology: Fourier
      transform infrared microspectroscopic imaging for objective and quantifiable
      assessment of liver biopsies.

PMID- 15740499
TI  - Polymorphism and squamous cell cancer of the esophagus.

PMID- 15740500
TI  - Spontaneous regression of a large hepatocellular carcinoma with skull metastasis.
AB  - Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon.
      This case of a 65-year-old Korean man with HCC and metastatic frontal bone mass
      that regressed after radiotherapy for frontal bone mass without any other
      therapeutic modalities is described. The clinical diagnosis of HCC was made
      because of the presence of a liver mass on abdominal computed tomography (CT)
      scan, high serum alpha-fetoprotein value and tissue diagnosis on frontal bone
      biopsy. The patient refused any other recommended treatments, but accepted the
      radiation therapy due to a painful frontal bone mass, and ingested mushroom
      called Phellinus linteus for one and a half years. Ten months after radiation
      therapy, he experienced a reduction in size of the frontal bone mass and
      improvement of lesions in the liver, sternum and ribs. The patient is alive and
      in good condition without any symptoms or tumor aggravation in August 2002. It
      was concluded that a rare case of spontaneous regression of HCC had occurred.

PMID- 15740501
TI  - Hepatocellular carcinoma associated with idiopathic portal hypertension: review
      of large nodules in seven non-cirrhotic portal hypertensive livers.

PMID- 15740502
TI  - Spontaneous bacterial peritonitis with a very high leukocyte count in ascitic
      fluid.

PMID- 15740503
TI  - Diagnosis of Barrett's esophagus in the Asian population.

PMID- 15740504
TI  - Time to bury the town-gown hatchet (but not in my back please).

PMID- 15740505
TI  - Laparoscopic live donor nephrectomy: an established alternative procedure for
      live renal donation.

PMID- 15740506
TI  - Training of surgeon scientists: are we insisting too much?

PMID- 15740508
TI  - Laparoscopic live donor nephrectomy.
AB  - BACKGROUND: The demand for renal transplants is greater than the available
      kidneys. Live donation is one way of increasing the supply. Laparoscopic removal
      of the donor kidney appears to reduce morbidity for the donors. Some who are
      hesitant because of the morbidity associated with open nephrectomy are willing to
      consider the laparoscopic donor nephrectomy. METHODS: Laparoscopic donor
      nephrectomy was offered to all but three donors since the commencement of the
      programme in 1997. Data were collected both prospectively and retrospectively for
      the first 120 donors. Venous and arterial anatomy was assessed preoperatively by
      computed tomographic angiography. RESULTS: All but four donor procedures were
      completed laparoscopically. Three of these were for bleeding that could not be
      safely controlled laparoscopically and the fourth was a planned conversion to
      deal with the renal vessels, in the first right nephrectomy. Two kidneys were
      lost due to arterial thrombosis and two underwent segmental infarction after the
      loss of one of two or three separately anastomosed vessels. Three recipients had
      delayed function and two of them required dialysis postoperatively. Other minor
      complications occurred but were uncommon. CONCLUSIONS: Laparoscopic live donor
      nephrectomy is safe for the donor and the transplant kidney. It offers the
      advantage of decreased morbidity for the donor, with a shorter hospital stay,
      earlier return to normal activity and, for some, early return to work.

PMID- 15740509
TI  - Using recombinant human thyroid-stimulating hormone for the diagnosis of
      recurrent thyroid cancer.
AB  - BACKGROUND: Recombinant human thyroid-stimulating hormone (rhTSH) has been
      suggested as a diagnostic agent in the diagnosis of recurrent thyroid cancer,
      instead of the current practice of thyroid hormone (THT) withdrawal. METHODS: An
      evidenced-based literature review was used as the basis for a cost-utility,
      decision-analytic model. Outcome measures were safety, efficacy (diagnostic
      performance and quality of life) and cost effectiveness of rhTSH. RESULTS: The
      literature search identified six comparative studies of rhTSH versus THT
      withdrawal. The most common adverse events associated with the use of rhTSH were
      headache (3.5-11.1%) and nausea (7.7-17%). When used as a diagnostic agent, the
      unadjusted sensitivity and specificity for rhTSH were 87% and 95%, respectively.
      Thus the use of rhTSH instead of THT withdrawal would result in a reduction in
      diagnostic accuracy, with 11% of patients' disease status being misclassified.
      Use of rhTSH resulted in a higher quality of life in the period prior to
      diagnostic testing than THT withdrawal (P < 0.001). When the impact of diagnostic
      performance, patient compliance to follow-up and modified quality of life were
      modelled over a 5 year time-frame, the incremental cost per QALY of rhTSH
      relative to THT withdrawal was $51 344.42. CONCLUSIONS: The use of rhTSH as a
      diagnostic agent appears to be safe but less diagnostically accurate and less
      cost-effective (on whole of healthcare cost basis) when used in the follow-up of
      patients with thyroid cancer who have had a previous negative radioiodine scan
      after thyroid hormone withdrawal.

PMID- 15740510
TI  - Severe acute respiratory syndrome in surgical patients: a diagnostic dilemma.
AB  - BACKGROUND: The diagnosis of severe acute respiratory syndrome (SARS) in surgical
      patients can potentially be missed based on current World Health Organization
      (WHO) case definitions. METHOD: We report a retrospective case series of 10
      surgical inpatients diagnosed with SARS following an outbreak in the surgical
      wards. Patients were included if they fulfilled the WHO case definition of
      probable SARS, had an active surgical problem and were admitted to the surgical
      wards during the outbreak period. Clinical histories, laboratory investigations
      and radiological findings were reviewed and analyzed. RESULTS: The mean age of
      the cohort was 57.6 years (range: 38-78 years). Nine patients had concomitant
      medical conditions. Three patients were in the early postoperative period, while
      the remaining seven were admitted for surgical related infections. All patients
      presented with fever, but only eight had accompanying respiratory symptoms.
      Lymphopenia and raised lactate dehydrogenase (LDH) was seen in seven patients.
      Eight patients had positive bacterial cultures. The primary abnormality on chest
      radiograph was air-space opacification. Rapid progression of radiological changes
      was seen in seven patients. Mortality rate for our cohort is 20%. CONCLUSION: The
      diagnosis of SARS in surgical patients differs from that previously described in
      normal patients. An apparent cause of fever and positive blood cultures cannot
      exclude a diagnosis of SARS. The current WHO case definition could result in
      delayed or even missed diagnosis. Early isolation of febrile patients with a
      positive contact history must be undertaken, even in the face of another
      identifiable cause.

PMID- 15740512
TI  - Non-sentinel lymph node metastases in breast cancer patients with metastatic
      sentinel nodes.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) has been shown to be relatively
      accurate in axillary nodal staging in breast cancer. In more than half of the
      patients with metastatic sentinel lymph node (SLN), the SLN was the only lymph
      node involved in the axilla. METHODS: A retrospective analysis was performed for
      those female Chinese breast cancer patients who underwent SLNB. All patients had
      axillary dissection after SLNB. Those patients with metastatic SLN were selected
      for analysis. Various tumour factors and SLN factors were analysed to study the
      association with residual lymph node metastasis. RESULTS: A total of 139 SLNB was
      performed. The success rate of SLN localization, false negative rate and accuracy
      were 92%, 9% and 95%, respectively. Fifty-five patients had metastases in the
      SLN. In 38 patients (69%), SLN was the only lymph node involved in the axilla.
      Tumours <3 cm, a single metastatic SLN, presence of micro metastases and the
      absence of extracapsular spread in the SLN were associated with the absence of
      metastasis in the non-sentinel lymph nodes. CONCLUSION: Sentinel lymph node
      biopsy is accurate in the nodal staging of Chinese breast cancer patients.
      Several factors such as tumour <3 cm, a single metastatic SLN, micro metastases
      and the absence of extracapsular spread in the sentinel node(s) are useful
      predictors for the absence of residual disease in the axilla. With further
      studies and verification, these factors may prove to be important in determining
      which patients with metastatic SLN will require further axillary treatment. Until
      such information is available, axillary dissection should be performed when
      positive sentinel nodes are found.

PMID- 15740513
TI  - Necrotizing fasciitis: analysis of 48 cases in South Auckland, New Zealand.
AB  - BACKGROUND: To assess the presentation, management and risk factors for mortality
      in necrotizing fasciitis at Middlemore Hospital in South Auckland, New Zealand.
      METHODS: A retrospective review of the medical records of patients presenting to
      Middlemore Hospital over a 6-year period (1997-2002) with a diagnosis of
      necrotizing fasciitis. RESULTS: Forty eight patients were identified. There were
      27 men and 21 women whose age ranged from 19 to 80 years (median 51 years) at
      presentation. Maori and Pacific Islanders accounted for 64% of total admissions
      despite making up only 31% of the referral population. Streptococcus Pyogenes was
      the most common bacterial isolate (54%). 31% of patients had polymicrobial
      infections. Sixty-two per cent of cases involved extremities. The median number
      of operations and length of stay were 4 and 31 days, respectively. Overall
      mortality was 29%. In multivariate analysis, delay in surgical intervention (P =
      0.015) and diabetes mellitus (P = 0.023) were found to be associated with
      increased mortality. Ethnicity, sex, type of pathogen, site of infection and
      increasing age did not affect mortality. CONCLUSION: Necrotizing fasciitis
      remains a significant problem in our community especially in the Maori and
      Pacific population. Early surgical debridement decreases mortality rates.

PMID- 15740514
TI  - Cost-effective method for laparoscopic choledochotomy.
AB  - BACKGROUND: Recent reports have noted that postoperative complications following
      open or laparoscopic choledochotomy for common bile duct (CBD) exploration are
      mainly related to the T-tube presence, and that there has been no trend of
      decrease in the laparoscopic era. Laparoscopic endobiliary stent placement with
      primary closure of the CBD has been proposed as a safe and effective alternative
      to T-tube placement. METHODS: Between January 1999 and January 2003, 53
      consecutive patients suffering from proven choledocholithiasis underwent
      laparoscopic common bile exploration (LCBDE) via choledochotomy. In the early
      period, a T-tube was placed at the end of the procedure (group A, n = 32) while,
      from June 2001 onwards, laparoscopic biliary stent placement and primary CBD
      closure were chosen as the drainage method (group B, n = 21). RESULTS: Six
      patients developed T-tube-related complications postoperatively. Univariate
      analysis revealed statistically significant lower morbidity rate and shorter
      postoperative hospital stay for the stent group. Although not statistically
      significant, a median saving of 780 UK pounds per patient was observed in the
      stent group. CONCLUSION: Biliary endoprosthesis placement following laparoscopic
      choledochotomy avoids the well-known complications of a T-tube, leading to a
      shorter postoperative hospital stay. The method is safe and effective and it
      should also be considered as cost-effective compared to T-tube placement. Further
      studies are required in order to document cost-effectiveness of the method.

PMID- 15740515
TI  - Bilateral ankle blocks: a prospective audit.
AB  - BACKGROUND: There are significant advantages to the practice of bilateral ankle
      block. However, clinicians are reluctant to employ this technique due to concerns
      over reliability, local anaesthetic longevity and toxicity, surgical efficiency,
      and patient comfort. METHODS: Sixty-six patients undergoing bilateral ankle
      blocks during mid- and forefoot surgery were audited to determine success rate,
      local anaesthetic safety and efficacy, and patient acceptance. Intravenous
      sedation was administered both during insertion of ankle blocks and
      intraoperatively, as requested by the patient and as deemed necessary by the
      anaesthetist. The choice of local anaesthesia was either a 50/50 mixture of
      lignocaine 1.5% plain and ropivacaine 7.5 mg/mL, ropivacaine 7.5 mg/mL alone or
      ropivacaine 7.5 mg/mL and clonidine 1 microg/kg. RESULTS: A total of 89% of
      patients had a successful bilateral ankle block. Ropivacaine and clonidine
      combination, ropivacaine, and ropivacaine and lignocaine combination provided a
      mean length of action of 17 h, 14 h and 8 h, respectively. No adverse local
      anaesthetic events were reported. Sixty-one per cent of patients remembered
      intraoperative events; only one patient would choose not to have the procedure
      performed again under ankle blocks. CONCLUSIONS: The present audit demonstrates
      that bilateral ankle blocks are a safe and efficient technique. With appropriate
      doses of sedative drugs both during insertion of the ankle block and surgery,
      patients remain comfortable.

PMID- 15740516
TI  - Inguinal hernia repair with the Kugel patch.
AB  - BACKGROUND: The Kugel hernia patch (Davol, Cranston, RI, USA) for treatment of
      inguinal hernias is a minimal access technique of inguinal herniorrhaphy, which
      aims to combine the utility of the open operation with the advantages of the
      laparoscopic procedures. The aim of the present study is to report an initial
      experience of a cohort of patients with inguinal hernias undergoing repair using
      this technique. METHODS: A prospective series of 107 inguinal hernia repairs
      performed between January 2000 and October 2003 in 96 patients, using the Bard
      Kugel hernia patch were entered into the study. Patient comfort, complications,
      activity levels postoperations and early recurrence were evaluated. RESULTS: The
      median age was 76 years (range 23-88 years). There were 107 inguinal hernias
      repaired. There were 11 bilateral, 39 left and 46 right sided hernias, 12 were
      recurrent. There were no major complications. There were no early recurrences. At
      6 and 12 months there were one and two hernia recurrences, respectively. A
      further recurrence was noted at 2 years. There was no consistent relationship
      between having hernia surgery and loss of mobility. There was no difference in
      straight leg raising noted following surgery compared to the patients'
      preoperative score. Ability to shower, dress, reach the toilet or perform
      housework by day 7 returned to normal. Shopping activities were resumed by day 30
      in all patients. CONCLUSIONS: The Kugel hernia operation is associated with
      minimal postoperative pain and rapid return to normal activity. There is a modest
      hernia recurrence rate, which needs to be addressed.

PMID- 15740517
TI  - Complications of transrectal versus transperineal prostate biopsy.
AB  - BACKGROUND: There are two established techniques of prostate biopsy: the more
      widely used transrectal technique, and the transperineal technique. Although the
      transrectal technique is faster, it is reported to have an increased risk of
      septic complications, which may be life threatening. The present study compares
      complication rates of both techniques at Nambour General Hospital. METHODS: The
      present retrospective study was performed by reviewing all available medical
      charts of men who underwent prostate biopsy during the years 1996-2001. The
      following data were recorded in a database: date of birth; digital rectal
      examination findings; serum prostate specific antigen (PSA); biopsy technique;
      number of cores taken; number of positive cores; Gleason grade and score;
      complications. Results were tabulated and simple statistical analysis performed
      to compare both groups. RESULTS: A total of 197 biopsies was included in the
      study, with 81 transperineal biopsies in 75 men, and 116 transrectal biopsies in
      103 men. There was no statistically significant difference in complication rates,
      including sepsis, between transrectal biopsy and transperineal biopsy. The rate
      of sepsis was 1.2% for the transperineal technique, and 0% for the transrectal
      technique (P = 0.411, Fisher exact test). Overall complication rates were 22.2%
      for transperineal technique and 19.8% for transrectal technique (P = 0.773,
      Fisher exact test). CONCLUSION: Although the present study was limited by
      retrospective design and size it suggests that both techniques are equally safe.
      A review of medical literature supports a tranperineal approach to patients who
      will tolerate sepsis poorly, or who have a suspected inflammatory cause of their
      raised PSA.

PMID- 15740518
TI  - Sinus of Valsalva aneurysm: surgical approaches to complicated cases.
AB  - BACKGROUND: The authors herein report surgical experience with the aneurysms of
      sinus of Valsalva (SVA) complicated by coexisting pathologies. METHODS: Eight
      patients aged between 11 and 55 years underwent surgical repair of SVA. The
      aneurysms originated from the right coronary sinus in four patients, from the non
      coronary sinus in four patients and from the left in one patient (one patient had
      aneurysms originating from both the left and right sinuses). Six of the aneurysms
      were ruptured into the right atrium (n = 3), right ventricle (n = 2) and left
      ventricle (n = 2). Aortic insufficiency (AI; n = 3), ventricular septal defect (n
      = 2), atrial septal defect (n = 4), Marfan's syndrome (n = 2), pulmonary stenosis
      (n = 1) and aortic stenosis (n = 1) were the coexisting anomalies. Double-chamber
      exposure (right atrial/ventricle and aortic) was used in all of the patients.
      Patch closure was preferred for defect closure. In three patients with AI, valve
      replacement was necessary. Two patients with endocarditis in New York Heart
      Association classes III-IV underwent urgent operation. RESULTS: The patient with
      annular narrowing was the only in-hospital death due to severe infection. The
      survivors were followed up for 85 months (range: 6-156 months). In two patients
      with Marfan's syndrome reoperation was necessary. All the surviving patients were
      asymptomatic with no unfavourable consequences. CONCLUSIONS: Although SVA can be
      treated successfully with low operative risk, the factors that influence patient
      outcome include infective endocarditis, Marfan's syndrome and the preoperative
      functional status of the patient.

PMID- 15740519
TI  - Evolution of management for Budd-Chiari syndrome: a team's view from 2564
      patients.
AB  - AIM: Exploring the development of therapy for a formerly rare and life
      threatening disorder, Budd-Chiari syndrome (BCS). METHODS: From 1981 to 2003,
      2677 patients with BCS were admitted including 2546 cases that underwent
      intervention. Therapeutic means included 170 membranotomies, 181 cavoatrial
      shunts, 312 mesoatrial shunts including mesocavoatrial shunt, 67 mesojugular
      shunts, 232 radical resections, 1289 PTA, and 295 miscellaneous procedures.
      RESULTS: Patients treated in the first decade had an effective rate of 77.7%,
      patency for various approaches was approximately 60-90% at 7 years. In our early
      experience, 55.7% patients underwent shunts, 26.1% had the transcardiac
      membranotomy and only 0.8% the interventional modality. Recently this has shifted
      to 16.2%, 5.2%, and 55.6%, respectively (P < 0.01). In the early phase, 11.6% of
      patients were classified as stage I (less clinical severity), and 28.6% patients
      in stage IV (most severe). In contrast, recent patients, they were 56.1% and 4.8%
      (P < 0.01). CONCLUSION: Chronologically, therapy has evolved from the relatively
      simple to the more complex (such as variety of shunts and radical correction)
      procedures, and finally, the interventional approaches as the main modality.
      However, for patients with type II (long segment occlusion in the inferior vena
      cava), major procedures maintain an essential role, especially the mesocavoatrial
      shunt. For those with type III (the HV lesions), shunts remain the procedures of
      choice. This increased use of the interventional methods is a reflection of
      greater clinical awareness and more frequent detection of much less severe cases.
      In stark contrast is declining numbers of advanced cases, signalling a landmark
      breakthrough in the management of BCS.

PMID- 15740520
TI  - Anal abscesses and fistulas.
AB  - Anal abscesses and fistulas are a common part of surgical practice. Most
      abscesses simply need to be drained and most fistulas can be safely laid open.
      Excessive probing should not be attempted when draining abscesses as this may
      lead to iatrogenic fistulas. A small percentage of fistulas are complex and very
      challenging to manage. Management involves an accurate diagnosis and a balance
      between eradication of the fistula and maintenance of continence. A decision
      should be made, based on clinical evaluation and anal ultrasound (if available),
      whether the fistula can be laid open. If it cannot be laid open, a loose seton is
      placed and the sepsis is allowed to settle. Once the sepsis is quiescent, a
      definitive repair can be attempted. There are various techniques available
      including rectal advancement flap, fibrin glue and cutaneous flaps all of which
      are discussed.

PMID- 15740521
TI  - Does L-arginine induce intestinal adaptation by epithelial growth factor?
AB  - BACKGROUND: To evaluate whether L-Arginine has an effect on endogenous epidermal
      growth factor secretion and intestinal adaptation in massive small bowel
      resection an experimental study was performed. METHODS: Fourteen albino Wistar
      rats weighing 250-300 g were used for the study. After performing 50% small bowel
      resection and anastomosis the rats were randomly divided into two groups. The
      first group received 500 mg/kg/day of L-Arginine intraperitoneally for 14 days
      just after the surgical procedure. The control group received isotonic saline
      instead. Body weight measurement was preformed daily. At the end of the second
      postoperative week all rats underwent relaparotomy. Small bowel was resected for
      histopathological examination. Levels of epidermal growth factor were measured by
      enzyme-linked immunosorbent assay in serum, saliva, and urine at the end of
      second postoperative week in both groups. RESULTS: The weight gain was higher in
      the L-Arginine treated group (P < 0.05). Serum, saliva and urinary epidermal
      growth factor levels were significantly higher at the end of the second week
      compared to the control group (P < 0.05). The villus height was higher on
      histopathological examination in L-Arginine treated group compared to the control
      group (P < 0.05). CONCLUSION: L-Arginine resulted in a better intestinal
      adaptation after massive bowel resection. The high levels of epidermal growth
      factor in body fluids of L-Arginine treated rats could be the explanation for
      this effect.

PMID- 15740523
TI  - Fibrous dysplasia of the temporal bone.

PMID- 15740522
TI  - Effect of dexamethazone on hepatic vascular response in experimental sepsis.
AB  - BACKGROUND: The aim of the present study was to evaluate the effect of
      dexamethasone-pretreatment on the hepatic artery and portal vein of septic rats,
      which were generated by lipopolisaccarides (LPS) intraperitoneal injection.
      METHOD: Thirty-six albino Wistar rats were used and constructed as LPS (n = 12),
      control (n = 12), dexamethazone-pretreatment (n = 6) and dexamethazone-control (n
      = 6) groups. Hepatic artery and portal vein rings were excised and placed in
      Krebs-Henseleit solution. Vessel rings were contracted with phenylephrine adding
      to the organ chamber in cumulative doses. Then the contraction-response curves
      were drawn. RESULTS: In the LPS group, phenylephrine evoked contractions were
      reduced in both hepatic artery and portal vein rings in comparison to the control
      group. In the dexamethasone-control group, phenylephrine-evoked contractions were
      increased but not significantly. Dexamethasone-pretreatment increased the
      phenylephrine-evoked contractions close to the values of control group for both
      types of rings. CONCLUSIONS: Dexamethasone pretreatment corrected the vascular
      hyporeactivity to phenyleprine in isolated portal vein and hepatic artery rings
      prepared from the LPS treated rats in experimental sepsis. This might have
      occurred as a result of inhibition of inducible nitric oxide synthase expression.

PMID- 15740524
TI  - Gastrointestinal haemorrhage complicating small bowel neurofibromatosis.
AB  - A case of acute gastrointestinal haemorrhage in a patient with systemic
      neurofibromatosis is presented. The bleeding was localized using mesenteric
      angiography and small bowel enema to a segment of ileum with multiple smooth
      muscle neurofibromata. The patient had a complete recovery after the resection
      and remained asymptomatic at 2 years follow up. Small bowel neurofibromatosis is
      a rare but important differential in gastrointestinal haemorrhage. Early
      diagnosis and surgery are vital for patient survival.

PMID- 15740525
TI  - Unequal access to breast-conserving surgery.

PMID- 15740526
TI  - RE: Management of colorectal cancer patients in Australia: the National
      Colorectal Cancer Care Survey.

PMID- 15740527
TI  - Cerebral amyloid angiopathy causing non-haemorrhagic mass effect.

PMID- 15740528
TI  - Laparoscopic hepatectomy for hepatocellular carcinoma: a caution.

PMID- 15740529
TI  - Coronary artery bypass grafting with valvular heart surgery after pneumonectomy.

PMID- 15740530
TI  - Incidental discovery of massive hepatic adenomatosis.

PMID- 15740531
TI  - Review article: psychosocial factors in the quality of life of patients with
      inflammatory bowel disease.
AB  - Information on quality of life in inflammatory bowel disease is limited. Despite
      the clear importance of this topic to patients, quality of life measurement is
      seldom undertaken in day-to-day management of patients or included in clinical
      trials. Although previous reviews have dealt with quality of life, the area of
      psychosocial functioning has not been specifically addressed. The aim of this
      study was to review the psychosocial factors affecting quality of life in
      patients with inflammatory bowel disease, using an electronic search of MEDLINE,
      EMBASE, CINAHL and psycINFO. Of the 751 articles identified by the search, 107
      were considered relevant and included in the review. A number of psychosocial
      factors appear to be important, including gender, socioeconomic status, ethnicity
      and perceived stress. To improve the quality of life in patients with
      inflammatory bowel disease, clinicians' attention needs to be drawn towards this
      subject, with an awareness of those patient groups more vulnerable to impaired
      quality of life. These identified variables also represent important factors,
      which should be adjusted for when conducting research into quality of life in
      these patients.

PMID- 15740532
TI  - Impact of pregnancy on the clinical activity of Crohn's disease.
AB  - BACKGROUND: The impact of pregnancy on Crohn's disease activity has been poorly
      investigated. AIM: To determine the effect of pregnancy on Crohn's disease
      activity from the retrospective analysis of a cohort of women who had a regular
      clinical follow-up. METHODS: Seventy pregnancies occurring in 61 women were
      studied. The Harvey-Bradshaw index was determined during the four quarters
      preceding each pregnancy, the three quarters of pregnancy and the four quarters
      following delivery. RESULTS: The mean Harvey-Bradshaw index during pregnancy
      [0.68 (0.18), mean (S.E.M.)] was significantly lower than that of the year
      preceding pregnancy [0.98 (0.16), P = 0.03] and that of the year following
      delivery [1.10 (0.17), P = 0.04]. In non-smoking women (48 pregnancies), there
      was no significant change of Harvey-Bradshaw index between these intervals.
      Whereas in those who smoked (22 pregnancies), most of whom reduced tobacco
      consumption during pregnancy, the mean Harvey-Bradshaw index during pregnancy was
      significantly reduced compared with that of the year following delivery [0.58
      (0.20) vs. 1.60 (0.33), P = 0.01]. The use of drugs was significantly lower
      during pregnancy. CONCLUSIONS: Crohn's disease activity is mildly but
      significantly lower during pregnancy. The reduction of tobacco consumption during
      pregnancy in smoking women may play an important role in this improvement.

PMID- 15740533
TI  - Systematic review: the liver in coeliac disease.
AB  - BACKGROUND: For over a decade isolated reports have noted liver histology and
      biochemistry changes in patients with coeliac disease. The prevalence and
      response to treatment is clinically important. AIM: To outline the frequency and
      significance of liver abnormalities in coeliac disease. METHODS: A Medline search
      using Ovid-Coeliac/Coeliac (exp) and liver disease (exp) was completed of English
      references published during 1966-June 2003. Bibliographic references and other
      appropriate sources were also searched. RESULTS: Six studies reported liver
      biochemistry in 591 patients; 248 patients had abnormal results. Elevated
      transaminases were the most frequently reported abnormality. A gluten-free diet
      produced resolution of elevated transaminases in 115 of 130 patients. There was a
      greater than expected association with primary biliary cirrhosis and advanced
      liver disease. CONCLUSIONS: Mildly abnormal liver biochemistry is frequent in
      untreated coeliac disease and may provide a key to the diagnosis. Routine
      investigations for undiagnosed liver disease should include tissue
      transglutaminase testing. Left untreated, coeliac-induced hepatitis may rarely
      progress to end-stage liver disease. Primary biliary cirrhosis is clearly linked
      to coeliac disease. The full story of these linkages is yet to be written.

PMID- 15740535
TI  - Severe haemorrhage following abdominal paracentesis for ascites in patients with
      liver disease.
AB  - BACKGROUND: Bleeding is a recognized complication of abdominal paracentesis.
      Special concern has been raised when it is performed in patients with liver
      failure because of coagulation disorders and collaterals in the abdominal wall.
      AIM: To assess the clinical characteristics of patients who developed
      haemorrhagic complications after paracentesis. METHODS: We reviewed all cases of
      severe haemorrhage occurring after paracentesis in patients admitted to the Liver
      Unit of our institution between 1994 and 2004. RESULTS: Nine cases were
      identified among 4729 procedures. The occurrence of severe haemorrhage
      represented 0.19% of all procedures with a death rate of 0.016%. Bleeding was not
      related to operator experience, elevated international normalized ratio or low
      platelets. It occurred in patients with high model for end-stage liver disease
      and Child-Pugh scores. Furthermore, some degree of renal failure was present in
      all but one patient. CONCLUSION: Severe haemorrhage after abdominal paracentesis
      in patients with liver disease occurs in 0.2% of cases. It occurs in patients
      with severe liver failure and is often associated with significant pre-existing
      renal dysfunction.

PMID- 15740534
TI  - Relationship between serum ferritin, hepatic iron staining, diabetes mellitus and
      fibrosis progression in patients with chronic hepatitis C.
AB  - BACKGROUND: Chronic infection with the hepatitis C virus affects over 170 million
      individuals worldwide and 20% of patients develop cirrhosis after 20 years.
      Increased iron stores and hepatic iron content have been suggested to be
      important in fibrosis progression. The increased prevalence of diabetes mellitus
      has been associated with increased iron deposits in patients with chronic
      hepatitis C. AIM: To assess the potential relationship between serum ferritin and
      hepatic iron staining and liver fibrosis in patients with chronic hepatitis C
      virus infection and whether these factors are increased in diabetic patients with
      hepatitis C virus. METHODS: This was a cross-sectional, multi-centre study
      involving hospitals in the north-east of London between 1992 and 2003. Chronic
      hepatitis C patients with a liver biopsy and data concerning age, sex, basal
      metabolic index, diabetes mellitus or impaired glucose tolerance, alcohol intake,
      serum ferritin level and ethnicity were enrolled. Each biopsy was scored for
      fibrosis and stained for hepatic iron. RESULTS: Three hundred and thirty nine
      patients (200 Caucasian; 139 Asian) were enrolled. Fifty three patients had no
      fibrosis, 131 had mild fibrosis (stage one to two Modified Ishak), 68 moderate
      fibrosis (stage three to four) and 87 cirrhosis (stage five to six). 4.4% of
      patients had elevations in serum ferritin, whilst 11% had increased hepatic iron
      staining. The serum ferritin and hepatic iron staining were unrelated to the
      degree of fibrosis. Serum ferritin was significantly higher in patients with
      diabetes or impaired glucose tolerance compared to non-diabetics. No association
      was seen between diabetes and hepatic iron staining. CONCLUSIONS: Many patients
      with chronic hepatitis C virus infection may have elevated serum ferritin and/or
      iron deposition within the liver. However, both played no significant role in the
      progression of hepatitis C virus related liver injury. The association between
      chronic hepatitis C virus infection and type II diabetes mellitus exists, however
      the biological mechanism of this association still remains to be elucidated.

PMID- 15740536
TI  - Adefovir dipivoxil added to ongoing lamivudine therapy in patients with
      lamivudine-resistant hepatitis B e antigen-negative chronic hepatitis B.
AB  - BACKGROUND: Long-term treatment with lamivudine is required to control viral
      replication in patients with hepatitis B e antigen-negative chronic hepatitis B,
      but is associated with a high rate of viral resistance. The role of adefovir
      dipivoxil in these patients has not been definitively evaluated. AIM: To address
      the role of adefovir in the management of patients with lamivudine-resistant
      hepatitis B e antigen-negative chronic hepatitis B. METHODS: Patients were
      assigned to receive adefovir 10 mg once daily plus ongoing lamivudine 100 mg once
      daily for 52 weeks. The primary end point was reduction in serum hepatitis B
      virus DNA level (hepatitis B virus DNA response). Secondary end points included
      the proportion of patients with undetectable hepatitis B virus DNA at week 52
      (complete virological response) and the percentage of patients with normalization
      of alanine transferase level at week 52 (biochemical response). RESULTS: A total
      of 49 consecutive patients were enrolled in this study. After 52 weeks of
      treatment, all patients had an hepatitis B virus DNA response and 57.1% had
      complete virological response. Biochemical response occurred in 75.6% of
      patients. CONCLUSIONS: Administration of adefovir in patients with lamivudine
      resistant chronic hepatitis B results in significant suppression of viral
      replication. Nevertheless, continuous therapy will probably be needed in order to
      maintain remission in these patients.

PMID- 15740537
TI  - Dynamic decision analysis to determine optimal treatment duration in chronic
      hepatitis C.
AB  - BACKGROUND: Current guidelines for stopping treatment of chronic hepatitis C are
      based on hepatitis C ribonucleic acid measurements at 12 and 24 weeks. AIM: To
      explore an alternative approach for making individualized recommendations about
      treatment duration, based on simple alanine aminotransferase tests and on cost
      per-cure. METHODS: We analysed individual patient data from 13 randomized,
      controlled trials with interferon alone or combined with ribavirin. Using
      multiple logistic regression, we built a model that estimated the probability of
      sustained virological response for treatment durations of 24 and 48 weeks.
      Decisions to prolong treatment were based on an increase in probability of
      sustained virological response. If the increase was 10%, the cost-per-cure became
      decisive with a limit of 50,000. RESULTS: Noncirrhotics with genotype 2 or 3 did
      not benefit when treatment was continued beyond 24 weeks. Sustained virological
      response rates in cirrhotic patients increased by 14-47% if treatment was
      continued up to 48 weeks. In noncirrhotic genotype 1 or 4 patients who had
      elevated alanine aminotransferase levels at week 4, the probability of sustained
      virological response increased by <10% if treatment was continued up to 48 weeks;
      the cost-per-cure for these patients would exceed 50,000. CONCLUSION: The
      dynamics of alanine aminotransferase levels and cost-per-cure provides a useful
      alternative to determine the duration of therapy in chronic hepatitis C.

PMID- 15740538
TI  - Easy-to-use, accurate and flexible individualized Bayesian limited sampling
      method without fixed time points for ciclosporin monitoring after liver
      transplantation.
AB  - BACKGROUND: New methods to estimate the systemic exposure to ciclosporin such as
      the level 2 h after dosing and limited sampling formulas may lead to improved
      clinical outcome after orthotopic liver transplantation. However, most strategies
      are characterized by rigid sampling times. AIM: To develop and validate a
      flexible individualized population-pharmacokinetic model for ciclosporin
      monitoring in orthotopic liver transplantation. METHODS: A total of 62 curves
      obtained from 31 patients at least 0.5 year after orthotopic liver
      transplantation were divided into two equal groups. From 31 curves, relatively
      simple limited sampling formulas were derived using multiple regression analysis,
      while using pharmacokinetic software a two-compartment population-pharmacokinetic
      model was derived from these same data. We then tested the ability to estimate
      the AUC by the limited sampling formulas and a different approach using several
      limited sampling strategies on the other 31 curves. The new approach consists of
      individualizing the mean a priori population-pharmacokinetic parameters of the
      two-compartment population-pharmacokinetic model by means of maximum a posteriori
      Bayesian fitting with individual data leading to an individualized population
      pharmacokinetic limited sampling model. From the individualized pharmacokinetic
      parameters, AUC(0-12h) was calculated for each combination of measured blood
      concentrations. The calculated AUC(0-12h) both from the limited-sampling formulas
      and the limited-sampling model were compared with the gold standard AUC(0-12h)
      (trapezoidal rule) by Pearson's correlation coefficient and prediction precision
      and bias were calculated. RESULTS: The AUC(0-12h) value calculated by
      individualizing the population-pharmacokinetic model using several combinations
      of measured blood concentrations: 0 + 2 h (r(2) = 0.94), 0 + 1 + 2 h (r(2) =
      0.94), 0 + 1 + 3 h (r(2) = 0.92), 0 + 2 + 3 h (r(2) = 0.92) and 0 + 1 + 2 + 3 h
      (r(2) = 0.96) had excellent correlation with AUC(0-12h), better than limited
      sampling formulas with less than three sampling time points. Even trough level
      with limited sampling method (r(2) = 0.86) correlated better than the level after
      2 h of dosing (r(2) = 0.75) or trough level (r(2) = 0.64) as single values
      without limited sampling method. Moreover, the individualized population
      pharmacokinetic model had a low prediction bias and excellent precision.
      CONCLUSION: Multiple rigid sampling time points limit the use of limited sampling
      formulas. The major advantage of the Bayesian estimation approach presented here,
      is that blood sampling time points are not fixed, as long as sampling time is
      known. The predictive performance of this new approach is superior to trough
      level and that after 2 h of dosing and at least as good as limited sampling
      formulas. It is of clear advantage in busy out-patient clinics.

PMID- 15740539
TI  - Morphological changes in human gastric tumours after eradication therapy of
      Helicobacter pylori in a short-term follow-up.
AB  - BACKGROUND: It is controversial as to whether the development of gastric cancer
      is influenced by Helicobacter pylori eradication. If eradication itself
      influences the tumour morphology, this may affect the tumour discovery rate. AIM:
      To investigate the morphological changes in the gastric neoplasm after H. pylori
      eradication. METHODS: We studied 37 patients with eradication therapy. After a 1
      month follow-up, endoscopic re-evaluation was performed and the appearance was
      compared with first image. All lesions were resected endoscopically, and were
      subjected to histological assessment and to immunohistochemistry. Serum gastrin
      levels were determined before and after eradication. RESULTS: Twenty-nine of 37
      patients underwent successful eradication. The appearance of 11 lesions (33% of
      33 lesions) became indistinct after successful eradication. All lesions were of
      the superficial-elevated type and the height of the lesions decreased. We
      detected normal columnar epithelium over the neoplasm in eight of the lesions.
      Higher expression of single-stranded deoxyribonucleic acid in the deep area was
      characteristic in tumours with an indistinct appearance. These changes did not
      correlate with the serum gastrin levels. CONCLUSIONS: The morphology of the
      gastric neoplasm change after eradication in the short-term. This may contribute
      to the decreased tumour discovery rate.

PMID- 15740540
TI  - Occurrence and risk factors for benign epithelial gastric polyps in atrophic body
      gastritis on diagnosis and follow-up.
AB  - BACKGROUND: Benign epithelial gastric polyps have been reported to be more common
      in atrophic body gastritis. The role of Helicobacter pylori infection in the
      induction of gastric atrophy is well-known. The development of hyperplastic
      polyps may be in relation to H. pylori infection. AIM: To investigate occurrence
      of benign epithelial gastric polyps in atrophic body gastritis patients at
      diagnosis and follow-up, and the role of H. pylori and other risk factors for the
      development of benign epithelial gastric polyps. METHODS: A total of 259
      consecutive atrophic body gastritis patients included in a follow-up programme,
      of whom 202 were followed up for median period of 4 years (range: 2-11). At
      baseline and follow-up gastroscopies, the presence of benign epithelial gastric
      polyps was evaluated. Biopsies for histology were obtained from all detected
      benign epithelial gastric polyps. RESULTS: Frequency of benign epithelial gastric
      polyps in atrophic body gastritis patients were 4.6% at baseline and 5.9% at
      follow-up. About 91.7% were hyperplastic polyps. H. pylori infection was detected
      in 79.2% atrophic body gastritis patients with benign epithelial gastric polyps,
      and in 70.8% without benign epithelial gastric polyps. Smoking was more frequent
      among patients with benign epithelial gastric polyps [42% vs. 20%, OR 2.8 (95%
      CI: 1.2-6.9)]. CONCLUSIONS: Benign epithelial gastric polyps occur in about 5% of
      atrophic body gastritis patients, and the vast majority are hyperplastic polyps.
      Smoking habit, but not H. pylori infection, increases the risk for benign
      epithelial gastric polyps in atrophic body gastritis patients.

PMID- 15740541
TI  - A comparative study of the early effects of tenatoprazole 40 mg and esomeprazole
      40 mg on intragastric pH in healthy volunteers.
AB  - BACKGROUND: Tenatoprazole is a novel proton pump inhibitor with a seven-hour
      plasma half-life. AIM: To compare the effects of tenatoprazole 40 mg and
      esomeprazole 40 mg on intragastric acidity during the first 48 h in healthy
      volunteers. METHODS: This randomized two-period crossover study included 24
      Helicobacter Pylori-negative subjects; tenatoprazole 40 mg or esomeprazole 40 mg
      daily were given before breakfast for two consecutive days, with a 2-week wash
      out between the administration periods. Intragastric pH was monitored for 48 h.
      RESULTS: Over 48 h, tenatoprazole 40 mg exerted a more potent acid inhibition
      than esomeprazole 40 mg (median pH: 4.3 vs. 3.9, P < 0.08; per cent of time above
      pH 4: 57% vs. 49%, P < 0.03; proportion of subjects with at least half of the
      time above pH 4: 71% vs. 46%). These differences resulted from better night-time
      acid control with tenatoprazole 40 mg than esomeprazole 40 mg (first night median
      pH: 4.2 vs. 2.9, P < 0.0001; second night: 4.5 vs. 3.2, P < 0.0001). The duration
      of nocturnal acid breakthroughs was significantly reduced during both nights. In
      contrast, no significant difference was detected during the daytime periods
      between both regimens. CONCLUSION: Over the first 48 h, tenatoprazole 40 mg
      achieves a better overall and night-time control of gastric pH than esomeprazole
      40 mg. The translation of better early control of acidity into clinical benefits
      deserves further studies.

PMID- 15740542
TI  - Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in
      children: a randomized double-blind placebo-controlled trial.
AB  - BACKGROUND: Co-treatment with Saccharomyces boulardii appears to lower the risk
      of antibiotic-associated diarrhoea in adults receiving broad-spectrum
      antibiotics. AIM: To determine whether S. boulardii prevents antibiotic
      associated diarrhoea in children. METHODS: A total of 269 children (aged 6 months
      to 14 years) with otitis media and/or respiratory tract infections were enrolled
      in a double-blind, randomized placebo-controlled trial in which they received
      standard antibiotic treatment plus 250 mg of S. boulardii (experimental group, n
      = 132) or a placebo (control group, n = 137) orally twice daily for the duration
      of antibiotic treatment. Analyses were based on allocated treatment and included
      data from 246 children. RESULTS: Patients receiving S. boulardii had a lower
      prevalence of diarrhoea (> or =3 loose or watery stools/day for > or =48 h
      occurring during or up to 2 weeks after the antibiotic therapy) than those
      receiving placebo [nine of 119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95%
      confidence interval: 0.2-0.7]. S. boulardii also reduced the risk of antibiotic
      associated diarrhoea (diarrhoea caused by Clostridium difficile or otherwise
      unexplained diarrhoea) compared with placebo [four of 119 (3.4%) vs. 22 of 127
      (17.3%), relative risk: 0.2; 95% confidence interval: 0.07-0.5]. No adverse
      events were observed. CONCLUSION: This is the first randomized-controlled trial
      evidence that S. boulardii effectively reduces the risk of antibiotic-associated
      diarrhoea in children.

PMID- 15740543
TI  - Meta-analysis: upper gastrointestinal tolerability of valdecoxib, a
      cyclooxygenase-2-specific inhibitor, compared with nonspecific nonsteroidal anti
      inflammatory drugs among patients with osteoarthritis and rheumatoid arthritis.
AB  - AIM: To compare the incidence of abdominal pain, dyspepsia and/or nausea
      associated with valdecoxib, nonspecific nonsteroidal anti-inflammatory drugs and
      placebo in patients with rheumatoid arthritis and osteoarthritis. METHODS: Data
      from five randomized, double-blind 12-week trials were pooled. Independent risk
      factors for abdominal pain, dyspepsia and/or nausea were also determined.
      RESULTS: The final analysis consisted of 4394 patients. Nonspecific nonsteroidal
      anti-inflammatory drug users (n = 1185) received naproxen 1000 mg/day (n = 766),
      ibuprofen 2400 mg/day (n = 207) or diclofenac sodium 150 mg/day (n = 212).
      Valdecoxib users received 10 mg/day (n = 955), 20 mg/day (n = 851) or 40 mg/day
      (n = 430). A total of 973 patients received placebo. The nonspecific nonsteroidal
      anti-inflammatory drug group was most likely to report abdominal pain or
      dyspepsia, while the placebo group reported the highest incidence of nausea. The
      most important risk factors for abdominal pain, dyspepsia and/or nausea were
      nonspecific nonsteroidal anti-inflammatory drug use, gastrointestinal history of
      nonspecific nonsteroidal anti-inflammatory drug-related intolerance or
      gastroduodenal ulcers, osteoarthritis diagnosis, female gender and age <65 years.
      CONCLUSION: This pooled analysis demonstrates a clear decrease in dyspepsia and
      an improvement in upper gastrointestinal tolerability for patients with
      osteoarthritis and rheumatoid arthritis taking valdecoxib, even at
      supratherapeutic doses, compared with those taking nonspecific nonsteroidal anti
      inflammatory drugs over 12 weeks.

PMID- 15740544
TI  - Upper gastrointestinal tolerability of once weekly alendronate 70 mg with
      concomitant non-steroidal anti-inflammatory drug use.
AB  - BACKGROUND: Both oral bisphosphonates and non-steroidal anti-inflammatory drugs
      have the potential to irritate the upper gastrointestinal mucosa, and are
      frequently used by the same patient population. AIM: To determine the rate of
      upper gastrointestinal adverse events with once weekly alendronate 70 mg and
      concomitant non-steroidal anti-inflammatory drug use. METHODS: A post hoc
      analysis was performed on 222 patients who received both medications
      concomitantly during a 3-month placebo-controlled study. A total of 450 (224
      alendronate; 226 placebo) postmenopausal women and men with osteoporosis were
      randomized. Concomitant non-steroidal anti-inflammatory drug users were defined
      as patients who received > or =7 continuous days of any dose of a dual cyclo
      oxygenase-1 and cyclo-oxygenase-2 inhibiting non-steroidal anti-inflammatory
      drug, a selective cyclo-oxygenase-2 inhibitor, or aspirin. A survival analysis
      was performed, and significance assessed. Logistic regression was used to assess
      consistency of treatment effect on rate of upper gastrointestinal adverse events
      across non-steroidal anti-inflammatory drug subgroups. RESULTS: Similar
      percentages of alendronate (52.7%) and placebo (46.0%) patients used non
      steroidal anti-inflammatory drugs regularly. Among concomitant non-steroidal anti
      inflammatory drug users, 11 alendronate and 11 placebo patients experienced upper
      gastrointestinal adverse events (9.3% and 10.8%, respectively, P = 0.744).
      Logistic regression revealed no significant interaction (P = 0.722) between
      alendronate and concomitant non-steroidal anti-inflammatory drug use. CONCLUSION:
      Based on this subgroup analysis, once weekly alendronate 70 mg used concomitantly
      with non-steroidal anti-inflammatory drugs, did not increase upper
      gastrointestinal adverse events relative to placebo over 3-months.

PMID- 15740545
TI  - The European panel on the appropriateness of gastrointestinal endoscopy
      guidelines colonoscopy in an open-access endoscopy unit: a prospective study.
AB  - BACKGROUND: The demand for gastrointestinal endoscopy is increasing in most
      developed countries, resulting in an important rise in overall costs and waiting
      lists for endoscopic procedures. Therefore, adherence to appropriate indications
      for these procedures is essential for the rational use of finite resources in an
      open-access system. AIM: To assess indications and appropriateness of colonoscopy
      according to the European Panel on the Appropriateness of Gastrointestinal
      Endoscopy (EPAGE) criteria. METHODS: From May to June 2004, all consecutive
      patients referred to our Unit for open-access colonoscopy were considered for
      inclusion in this prospective study. Appropriateness of each colonoscopy was
      established according to the EPAGE criteria. In order to evaluate whether
      appropriateness of use correlated with the diagnostic yield of colonoscopy,
      relevant endoscopic findings were also recorded. RESULTS: A total of 350
      consecutive patients were included in the study. In 38 of them, the colonoscopy
      indication was not listed in the EPAGE guidelines and, consequently, they were
      not evaluated. In the remaining 312 patients, the indication for the procedure
      was considered inappropriate in 73 (23%) patients. Both referring doctor
      characteristics (specialty and health care setting) and patient data (age)
      correlated with appropriateness of endoscopy. The diagnostic yield was
      significantly higher for appropriate colonoscopies (42%) than in those judged
      inappropriate (21%) (P = 0.001). CONCLUSIONS: A noteworthy proportion of patients
      referred for colonoscopy to an open-access endoscopy unit are considered
      inappropriate because of their indication, with significant differences among
      specialties. These results suggest that implementation of validated guidelines
      for its appropriate use could improve this situation and, considering the
      correlation between appropriateness and diagnostic yield, even contribute to
      improve the prognosis of patients with colorectal diseases.

PMID- 15740546
TI  - Hospital health care resource utilization and costs of colorectal cancer during
      the first 3-year period following diagnosis in Switzerland.
AB  - BACKGROUND: In industrialized countries, colorectal cancer is a leading cause of
      morbidity and mortality. Decisions on colorectal cancer screening are based on
      cost-effectiveness analyses that rely on colorectal cancer cost studies.
      Additionally, the study of the resource utilization pattern may lead to cost
      saving strategies in the care of colorectal cancer. AIM: To estimate hospital
      resource utilization, the use of various therapy modalities and costs of
      colorectal cancer cases undergoing surgery during the first 3 years following the
      diagnosis at a Swiss university hospital. METHODS: Consecutive colorectal cancer
      patients from 1997 to 1998 were identified using the surgery database of the
      University Hospital of Basel and followed for a period of 3 years. In-hospital
      resource utilization and costs were retrieved from the computerized
      administrative records. Treatment outside of the hospital during the study period
      constituted an exclusion criterion. RESULTS: Eighty-three (94%) of 89 patients
      undergoing surgery for colorectal cancer were included in the study, 58 with
      colon cancer and 25 with rectal cancer. The average ages were 70.3 and 63.6
      years, respectively. Overall, 59% of the patients were treated with surgery
      alone, 27% also had chemotherapy and 15% received additional chemoradiotherapy.
      These percentages and resource utilization varied broadly between the two
      colorectal cancer groups. On average, patients were admitted to the hospital 2.7
      times and the hospital length of stay amounted to 35 days. They were visited by
      doctors 69 times, and examined with colonoscopy, ultrasonography and computerized
      tomography 2.7, 3.2 and 2.4 times, respectively. Mean costs incurred for rectal
      cancer (US dollars 40,230) were about 22% higher than for colon cancer patients
      (US dollars 33,079). Hospitalization and surgical therapy generated the greatest
      costs. Expenses were highest for the first year and with more severe disease
      stages at diagnosis. CONCLUSIONS: Colorectal cancer is an expensive disease.
      Economic analyses on screening should take into account the large resource
      utilization and cost variability by performing sensitivity analysis on broad cost
      ranges. Furthermore, they should consider stage shifting at diagnosis and include
      stage-specific costs.

PMID- 15740547
TI  - Therapeutic drug monitoring for everolimus in kidney transplantation using 12
      month exposure, efficacy, and safety data.
AB  - The aims of the current study were to determine whether therapeutic drug
      monitoring (TDM) might benefit kidney transplant recipients receiving everolimus,
      and to establish dosage recommendations when everolimus is used in combination
      with cyclosporine and corticosteroids. The analysis was based on data from 779
      patients enrolled in two 12-month trials. Everolimus trough concentrations >/=3
      ng/mL were associated with a reduced incidence in biopsy-proven acute rejection
      (BPAR) in the first month (p = 0.0001) and the first 6 months (p = 0.0001), and
      reduced graft loss compared with lower concentrations (4% vs. 20%, respectively).
      By contrast, cyclosporine in the standard concentration range had no impact on
      BPAR within the same timeframes. Most patients receiving everolimus 1.5 or 3 mg/d
      achieved trough concentrations above the therapeutic threshold of 3 ng/mL,
      regardless of reductions in cyclosporine dose. TDM simulation showed that just
      two dose adjustments would achieve median everolimus trough values >/=3 ng/mL in
      95% of patients during the first 6 months. This investigation indicates that
      improved efficacy is likely when TDM is considered as an integral component of
      the immunosuppressive strategy of everolimus.

PMID- 15740548
TI  - The long-term outcome of tacrolimus in cadaveric kidney transplantation from non
      heart beating donors.
AB  - Tacrolimus (Tac), developed in 1990, has been applied as an immunosuppressive
      agent for liver, heart, and kidney transplantation and is known to have more
      powerful immunosuppressive effects than cyclosporine (CyA). To evaluate the
      efficacy of Tac in cadaveric kidney transplants from non-heart beating donors, we
      present the long-term outcome of patients receiving kidneys with ischemic damage,
      and compared it with that of CyA. Between July 1990 and December 2000, 55
      patients with end-stage renal disease received kidneys from non-heart beating
      donors (Maastrichy category 3) and were treated with Tac and steroid
      immunosuppressive therapy. During the same period, we also performed 137 non
      heart beating cadaveric renal transplants treated with CyA-based
      immunosuppressive therapy. The patient survival rate was 98% at 1 yr and 96% at 3
      10 yr in the Tac group, and 97% at 1-3 yr, 93% at 5 yr and 85% at 10 yr in the
      CyA group. The graft survival rate was 91% at 1 yr, 80% at 3 yr, 63% at 5 yr and
      34% at 10 yr in the Tac group, and 88% at 1 yr, 75% at 3 yr, 63% at 5 yr and 49%
      at 10 yr in the CyA group. There was no significant difference in either patient
      or graft survival rates between the two groups. Acute early rejection in the Tac
      group was less than that in the CyA group but acute tubular necrosis was the same
      in both groups. This indicates that Tac is available for cadaveric kidney
      transplants from non-heart beating donors. In conclusion, Tac is available as an
      immunosuppressive agent even for kidney transplants from non-heart beating
      donors.

PMID- 15740549
TI  - Greater early pancreas graft loss in women compared with men after simultaneous
      pancreas-kidney transplantation.
AB  - BACKGROUND: Gender differences in graft survival has been reported after some
      types of organ transplantation, but not after pancreas transplantation. This
      study compares graft survival between women and men after simultaneous pancreas
      kidney transplantation (SPK). METHODS: All first time SPK (n = 163) transplants
      (109 M/54 F) performed between 1989 and 2000 at University of Nebraska Medical
      Center, where data was available, were analyzed for overall graft and patient
      survival. Graft failure was then subdivided into early (<6 months), and late (>6
      months), and compared between women and men. RESULTS: The 5-yr pancreas and
      kidney graft survival rates for all SPK recipients was 86% [95% confidence
      interval (CI) = 81-92%] and 87% (95% CI = 82-93%), respectively. While overall
      pancreas graft survival in women was similar to men (p = 0.16), early pancreas
      graft failure was greater in women than men (p = 0.010) with no one cause for
      failure predominant. There was no gender difference in late pancreas graft
      failure or in early, or late kidney graft failure in the same recipients. The
      gender difference was unexplained by differences in age, immunosuppression, body
      mass index (BMI), or diabetes duration between women and men. CONCLUSIONS: This
      is the first report of a gender difference in pancreas graft survival after SPK
      with greater early (<6 months) pancreas graft failure in women than men. With no
      gender difference in kidney graft failure in the same individuals, gender
      differences in immune responses are unlikely to be the cause. Multiple variables
      likely contribute.

PMID- 15740550
TI  - The effect of sirolimus on sex hormone levels of male renal transplant
      recipients.
AB  - BACKGROUND: It is unclear whether sirolimus, a newer immunosuppressive agent,
      widely used in renal transplantation, affects male sex hormone levels or sexual
      function. METHODS: Sex hormone profiles in male renal transplant recipients were
      obtained and compared between a sirolimus-treated group and a group not on
      sirolimus in a cross-sectional study. Both groups also completed a sexual
      dysfunction questionnaire. RESULTS: Sixty-six subjects were evaluated, 32 in the
      sirolimus group and 34 in the control group. Total testosterone level was
      significantly lower in the sirolimus group than the control group (393.3 +/- 188
      vs. 537.4 +/-232 pg/mL; p = 0.08) while follicle stimulating hormone and
      luteinizing hormone levels were significantly higher in the sirolimus group (12.8
      +/- 14 vs. 6.0 +/- 5, p = 0.013; 10.9 +/- 14 vs. 4.7 +/- 4, p = 0.018,
      respectively). There was a significant negative correlation between 24-h
      sirolimus trough and total testosterone levels (p < 0.03). By multiple regression
      analysis, use of sirolimus was independently associated with decreased total
      testosterone level. There was no significant difference in subjective sexual
      dysfunction as assessed by questionnaire scores between the two groups. There was
      no correlation between questionnaire scores and total testosterone level.
      CONCLUSION: Sirolimus is associated with decreased total testosterone levels in
      male renal transplant recipients. It is unclear whether sirolimus may affect
      other aspects of sexual function.

PMID- 15740551
TI  - Effects of mycophenolate mofetil on donor-specific antibody formation in renal
      transplantation.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is a routinely used immunosuppressive
      agent that selectively blocks T- and B-lymphocyte proliferation. The present
      study was designed to investigate the effects of this drug on human
      leukocyte(HLA) antibody production in general and donor-specific antibody (DSA)
      formation in particular in 154 recipients of renal allografts. PATIENTS AND
      METHODS: Renal allograft recipients were subdivided into three groups. Group 1
      patients (n = 60) had received MMF since transplantation in combination with
      either cyclosporin A or tacrolimus and steroids. Group 2 patients (n = 29) had
      received an MMF-free immunosuppressive regimen initially followed by addition of
      MMF some time later. Group 3 patients (n = 65) had received no MMF. Cyclosporin A
      or tacrolimus in combination with azathioprine and/or steroids were used for
      immunosuppression. DSA were demonstrated by enzyme-linked immunosorbent assay
      (ELISA) for detection of panel-reactive antibodies of HLA class I and II
      specificity. RESULTS: The HLA antibodies were found in 16.7%, 27.6% and 30.8% of
      transplant recipients in groups 1, 2 and 3, respectively. DSA were found in 8.3%,
      17.2% and 20.0%, and non-DSA in 10.0%, 20.7% and 24.6%, of patients in groups 1,
      2 and 3, respectively. CONCLUSION: The MMF reduces anti-HLA class I and II
      antibody production and consequently DSA production in renal allograft
      recipients. Our data indicate this effect to be more pronounced in patients given
      MMF immediately after transplantation than in those in whom MMF is introduced
      some time later. The presence of DSA in the serum of renal allograft recipients
      is associated with poorer graft function (higher serum creatinine and more
      rejection episodes).

PMID- 15740552
TI  - Feasibility of salvage liver transplantation for patients with recurrent
      hepatocellular carcinoma.
AB  - BACKGROUND: Recurrence is the most frequent cause of treatment failure after
      hepatocellular carcinoma (HCC) resection. Salvage liver transplantation is an
      alternative treatment for recurrent HCC. The transplantability for patients with
      recurrent HCC has not been well studied. STUDY DESIGN: This study sought to
      determine how many patients with recurrent HCC are still candidates for liver
      transplantation, and to ascertain the possible time from HCC recurrence to the
      loss of transplantability. In an university hospital setting, 154 of the 252
      patients receiving primary HCC resection, from January 1992 through December
      1996, had recurrence and were analyzed. The mean follow-up time was 6 years.
      Among the 154 patients, 74 patients (group 1) were not eligible for liver
      transplantation according to the Milan criteria, while 80 patients were eligible
      (group 2). Demographic characteristics of both groups were compared and the curve
      of transplantability was calculated. RESULTS: When compared with group 1
      patients, group 2 patients displayed more cirrhosis (p = 0.007), lower pTNM stage
      (p = 0.004), were older (p = 0.004), presented with smaller tumors (p < 0.001),
      and displayed a longer disease-free interval (p < 0.001). In group 1, only 47%
      (35/74) patients were eligible for liver transplantation at the time of index
      hepatectomy, in contrast to 84% (67/80) in the group 2 patients, p < 0.001. The
      median time from HCC recurrence to the time they were no longer transplantable
      was 38 months. The total time from the index HCC resection to the time of loss of
      transplantability was 83 months. CONCLUSION: In a cohort of patients after
      resection for their primary HCC, 33% patients had no recurrence and were not in
      need for liver transplantation in a mean follow-up of 72 months. About 52% of the
      patients with recurrent HCC still meet the criteria for liver transplantation.
      For patients with some certain characteristics, resection of the primary HCC may
      postpone the time of liver transplantation and prolong the time in which a
      suitable donor searched, while primary liver transplantation may be considered
      for those patients with factors of low transplantability after recurrence.

PMID- 15740553
TI  - Hypertension, antihypertensive agents and outcomes following renal
      transplantation.
AB  - Hypertension is common following renal transplantation and adversely affects
      graft and patient survival. However, strategies for antihypertensive drug therapy
      and target blood pressure have not been clearly defined. AIM: To assess the
      influence of achieved blood pressure and antihypertension drug therapy on graft
      and patient survival with the aim of identifying targets and event rates for
      future intervention studies. METHODS: We undertook a longitudinal follow up study
      of 634 renal transplant patients. Patients were surveyed in December 1994 and
      followed up after 102 months. Blood pressure (BP) was determined from the mean of
      three clinic readings and antihypertensive drug therapy recorded. RESULTS:
      Complete follow up data were available for analysis on 622 patients (57.2% male;
      mean age: 45.2 +/- 13.0 yr. There were 158 (25.4%) deaths and 115 (18.5%) death
      censored graft failures. Lower systolic and diastolic blood pressure were
      associated with better graft survival in the Kaplan-Meier analysis. Univariate
      analysis showed serum creatinine (HR 1.012, p < 0.001), duration of renal
      replacement therapy (HR 0.946, p = 0.012), age (HR 0.979, p = 0.014) and pulse
      pressure (HR 1.017, p = 0.044) to be predictors of graft survival with serum
      creatinine and duration of renal replacement therapy as the only significant
      factors in the multivariate analysis. Lower systolic and pulse pressure were
      associated with better patient survival in the Kaplan-Meier analysis. Age (HR)
      1.062, p < 0.0001), serum creatinine (HR 1.002, p = 0.021), diabetes (HR 3.371, p
      < 0.0001), and pulse pressure (HR 1.013, p = 0.036) were significant predictors
      of patient survival in the univariate and multivariate analysis. Patient survival
      was reduced with increasing number of antihypertensives (p < 0.05), as was graft
      survival (p < 0.05). Reduced patient and graft survival were seen in patients
      prescribed calcium channel antagonists (p < 0.01). There was no increased patient
      mortality in those patients on beta-blockers or angiotensin converting enzyme
      (ACE) inhibitors. CONCLUSION: Hypertension is a risk factor, which remains
      despite the use of anti-hypertensives, for reduced patient and graft survival.
      The risk was not significant when blood pressure was entered together with serum
      creatinine in the multivariate analysis. Beta-blockers may have a beneficial
      effect on cardiovascular mortality, and ACE inhibitors a beneficial effect on
      both patient and graft survival. There is a pressing need for interventional
      studies to assess the impact of blood pressure targets on patient and graft
      survival and the effect of individual agents on these outcomes.

PMID- 15740554
TI  - Predictors of improvement in renal function after calcineurin inhibitor
      withdrawal for post-liver transplant renal dysfunction.
AB  - BACKGROUND: Renal dysfunction after liver transplantation is a major management
      problem. Predictors of improvement in renal dysfunction after calcineurin
      inhibitor therapy (CNI) withdrawal and replacement with either mycophenolate
      mofetil (MMF) or azathioprine (AZA) have not previously been examined. METHODS:
      Retrospective analysis of 33 post-transplant patients with creatinine clearance
      (CrCl) below 50 mL/min who were changed from CNI to either MMF or AZA. Following
      CNI withdrawal patients were divided into two groups: those with improved CrCl
      after switching and those without, to identify the variables associated with
      improved renal function. RESULTS: Variables associated with improved CrCl were:
      absence of hypertension or diabetes, shorter time between transplantation and
      switch, deterioration in CrCl in months prior to switch and treatment with MMF
      (compared with AZA). CONCLUSIONS: Our findings suggest CNI withdrawal should be
      targeted to a subgroup of patients whose renal function is most likely to
      improve.

PMID- 15740555
TI  - Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared
      with mycophenolate mofetil.
AB  - Mycophenolic acid (MPA), the active moiety of mycophenolate mofetil (MMF), is
      routinely used as an adjunct immunosuppressant therapy in renal transplantation.
      Although highly effective, MMF therapy is associated with significant
      gastrointestinal adverse effects. Enteric-coated mycophenolate sodium (EC-MPS) is
      an advanced formulation delivering MPA. The enteric coat dissolves at pH > 5
      allowing for MPA delivery in the small intestine. A single-center, open-label,
      randomized, three-way crossover study of 24 stable Caucasian renal transplant
      patients receiving cyclosporine-based immunosuppression, compared the relative
      bioavailability of two EC-MPS doses (640 and 720 mg) with MMF (1000 mg). Both EC
      MPS doses delivered bioequivalent mean MPA exposure (AUC(0-infinity)) compared
      with 1000 mg MMF: 60.7 microg h/mL for 640 mg EC-MPS, 66.5 microg h/mL for 720 mg
      EC-MPS, and 63.7 microg h/mL for 1000 mg MMF. Median t(max) was significantly
      delayed for both EC-MPS doses compared with MMF (2.0 h vs. 0.75 h, respectively;
      p < 0.01), consistent with a functional enteric coating of EC-MPS. Furthermore,
      both EC-MPS doses were bioequivalent to 1000 mg MMF for AUC and C(max) for
      mycophenolic acid glucuronide. All three treatments were well tolerated. The EC
      MPS 720 mg dose most closely approximated the MPA exposure of 1000 mg MMF and was
      selected for subsequent phase III studies.

PMID- 15740556
TI  - Tobacco and alcohol use in lung transplant candidates and recipients.
AB  - Tobacco and alcohol use among lung transplant candidates and recipients is
      unknown. Our first goal was to describe tobacco and alcohol use before and after
      lung transplant in patients with cystic fibrosis (CF) and other pulmonary
      diseases (non-CF). Our second goal was to determine whether demographic
      variables, depression, anxiety and social support predicted tobacco and alcohol
      use. Self-report data from transplant candidates and recipients, and transplant
      nurse coordinator ratings of post-transplant smoking and drinking were utilized.
      Data from two samples were analyzed. Sample 1 comprised 219 patients being
      evaluated for lung transplant, and sample 2 comprised 45 transplant recipients
      who were 1-7 yrs post-transplant. The results from analyzing sample 1 indicated
      that 72% of non-CF patients and 16% of CF patients had a history of smoking
      cigarettes, and the majority of patients in both groups had consumed alcohol in
      the past. For CF patients, past smoking was related to higher depression scores,
      and past drinking was related to higher education and lower social support. For
      non-CF patients, a history of smoking was associated with being Caucasian and
      older. For CF patients, a history of drinking was associated with being older and
      less depressed, and for non-CF patients a history of drinking was associated with
      higher education and lower social support. Post-transplant 100% of recipients
      reported abstinence from tobacco, and over 60% reported abstinence from alcohol.
      Transplant coordinator ratings corroborated that no transplant recipients were
      using tobacco products or consuming alcohol in an excessive or problematic
      manner. For both groups, consuming alcohol after transplant was related to lower
      levels of social support. In conclusion, lung recipients remain abstinent from
      tobacco, and although over 30% of patients consume alcohol after transplant, it
      is not at problematic levels. Smoking and drinking behaviors were related to
      demographic variables, depression, and low social support.

PMID- 15740557
TI  - Outflow block secondary to stenosis of the inferior vena cava following living
      donor liver transplantation?
AB  - Although it is well known that outflow block is caused by stenosis or occlusion
      of hepatic vein anastomoses following living donor liver transplantation (LDLT),
      there have been few reports on inferior vena cava (IVC) stenosis following LDLT.
      In this paper, we report two cases of IVC stenosis and hepatic vein outflow block
      following right hepatic LDLT in the absence of stenosis of any of the
      anastomoses. Both patients presented with liver dysfunction, an ascitic fluid
      volume of approximately 2000 mL, and congestion in their biopsy specimens, and
      venocavography demonstrated IVC stenosis with gradients of more than 10 mmHg in
      patients with a dominant inferior right hepatic vein (IRHV) anastomosis. After a
      Gianturco expandable metallic stent successfully implanted in the IVC, the
      patient's liver function recovered and the volume of ascitic fluid decreased. The
      pathogenesis of hepatic vein outflow block secondary to IVC stenosis following
      LDLT may involve the anastomosis with the IRHV, which is the dominant draining
      vein of the graft and larger than the RHV, caudal to the IVC stenosis and a
      significant IVC pressure gradient that results in increased IRHV pressure. In
      conclusion, it is important to include hepatic vein outflow block in the
      differential diagnosis when patients who have undergone right hepatic LDLT in
      which anastomosis of the large IRHV has been performed develop manifestations of
      liver dysfunction.

PMID- 15740558
TI  - Late anastomotic leaks in pancreas transplant recipients - clinical
      characteristics and predisposing factors.
AB  - BACKGROUND: Anastomotic leaks after pancreas transplants usually occur early in
      the postoperative course, but may also be seen late post-transplant. We studied
      such leaks to determine predisposing factors, methods of management, and
      outcomes. RESULTS: Between January 1, 1994 and December 31, 2002, a total of 25
      pancreas transplant recipients at our institution experienced a late leak
      (defined as one occurring more than 3 months post-transplant). We excluded
      recipients with an early leak or with a leak seen immediately after an enteric
      conversion. The mean recipient age was 40.3 yr; mean donor age, 31.3 yr. The
      category of transplant was as follows: simultaneous pancreas-kidney (n = 5, 20%),
      pancreas after kidney (n = 10, 40%), and pancreas transplant alone (n = 10, 40%).
      At the time of their leak, most recipients (n = 23, 92%) had bladder-drained
      pancreas grafts; only two recipients (8%) had enteric-drained grafts. The mean
      time from transplant to the late leak was 20.5 months (range = 3.5-74 months). A
      direct predisposing event or risk factor occurring in the 6 wk preceding leak
      diagnosis was identified in 10 (40%) of the recipients. Such events or risk
      factors included a biopsy-proven episode of acute rejection (n = 4, 16%), a
      history of blunt abdominal trauma (n = 3, 12%), a recent episode of
      cytomegalovirus infection (n = 2, 8%), and obstructive uropathy from acute
      prostatitis (n = 1, 4%). Non-operative or conservative care (Foley catheter
      placement with or without percutaneous abdominal drains) was the initial
      treatment in 14 (56%) of the recipients. Such care was successful in nine (64%)
      of the 14 recipients; the other five (36%) required surgical repair after failure
      of conservative care at a mean of 10 d after Foley catheter placement. Of the 25
      recipients, 11 underwent surgery as their initial leak treatment: repair in nine
      and pancreatectomy because of severe peritonitis in two. After appropriate
      management (conservative or operative) of the initial leak, five (20%) of the 25
      recipients had a recurrent leak; the mean length of time from initial leak to
      recurrent leak was 5.6 months. All five recipients with a recurrent leak
      ultimately required surgery. CONCLUSIONS: Late anastomotic leaks are not
      uncommon; they may be more common with bladder-drained grafts. One-third of the
      recipients with a late leak had experienced some obvious preceding event that
      predisposed to the leak. For two-thirds of our stable recipients with bladder
      drained grafts, non-operative treatment of the leak was successful.

PMID- 15740559
TI  - Basiliximab lowers the cyclosporine therapeutic threshold in the early post
      kidney transplant period.
AB  - Early adequate cyclosporine exposure has been shown to predict low acute
      rejection rate in kidney transplantation. The aim of this study is to determine
      the importance of exceeding the early cyclosporine therapeutic exposure threshold
      with basiliximab induction. A retrospective analysis of 166 first cadaveric and
      non-identical live donor transplant recipients treated with or without
      basiliximab induction, Neoral, mycophenolate mofetil and prednisone, was
      performed. Adequate exposure was defined as a 2-h post-Neoral dose cyclosporine
      level (C2) >1700 ng/mL at day 3. The primary outcome was acute rejection within
      the first 6 months. In the no basiliximab (control) group (n = 74), rejection
      occurred in 23% (17 of 74) of recipients and was strongly associated with low
      cyclosporine exposure on day 3. Acute rejection occurred in 38% (11 of 29) with
      C2 <1700 ng/mL compared with 13% (six of 45) with C2 >/=1700 ng/mL (p = 0.014).
      In the basiliximab group (n = 92), rejection occurred in only 11% (10 of 92) of
      recipients and did not correlate with cyclosporine exposure. Acute rejection
      occurred in 10% (four of 40) with C2 <1700 ng/mL compared with 12% (six of 52)
      with C2 >/=1700 ng/mL (p = 0.81). Therefore achieving cyclosporine therapeutic
      targets by day 3 may not be required when anti-IL2 receptor antibody induction is
      used.

PMID- 15740560
TI  - Urinary tract infections after renal transplantation: a retrospective review at
      two US transplant centers.
AB  - Urinary tract infections (UTIs) are the most common infectious complication
      following renal transplantation. Previous studies uniformly report that renal
      transplant recipients develop UTIs more often than the general population, but
      widely differ on how frequently UTIs occur after transplantation. These studies
      also disagree on the risk factors associated with developing post-transplant
      UTIs, as well as the effect that UTIs may have on graft outcomes and patient
      mortality. We performed a retrospective cohort study including all the adult
      patients who received a renal transplant at two US transplant centers from
      January 1996 to December 2002 (500 patients). Two hundred and thirteen (43%)
      patients developed one or more post-transplant UTIs over a mean follow-up period
      of 42 months. Significant risk factors for post-transplant UTIs were advanced
      age, female gender, reflux kidney disease, use of azathioprine and cadaveric
      donor. UTIs did not increase risk for renal graft loss, but were associated with
      increased mortality (3.5 odds ratio, 95% confidence interval 1.68-7.23). We
      conclude UTIs may be associated with an increased mortality risk in renal
      transplant recipients. Prevention of UTIs in high-risk renal transplant patients
      or those with recurrent UTIs may possibly decrease post-transplant mortality.

PMID- 15740561
TI  - Rapamycin in patients with chronic renal allograft dysfunction.
AB  - PURPOSE: Nephrotoxicity of calcineurin inhibitors (CNI) complicates the
      management of chronic renal allograft dysfunction. Rapamycin is a promising
      immunosuppressive agent free of nephrotoxicity. The effect of conversion from CNI
      to rapamycin in recipients with chronic allograft dysfunction is still unclear.
      We investigated the effect of rapamycin in patients with chronic allograft
      dysfunction. METHODS: We conducted a prospective study on kidney transplant
      recipients with chronic allograft dysfunction. The patients were under classic
      CNI, mycophenolate mofetil, and prednisolone triple therapy. They had progressive
      deterioration of the allograft function. They were converted from CNI to
      rapamycin directly and observed for 6 months. The CNI serum levels before the
      conversion were within recommended range. Allograft function, clinical features
      and adverse effects were evaluated before and after the rapamycin conversion.
      RESULTS: A total of 16 patients were enrolled. Six of them (37.5%) failed to have
      a smooth conversion because of deterioration of allograft function and
      intractable adverse effects. Ten patients (62.5%) went through the 6-month
      observation period with improved graft function. The average reduction of serum
      creatinine was 27.7% (p < 0.001) in successful conversion. There were no
      significant differences on age, gender, lipid profile, sugar control, and
      rapamycin levels between successful and failed conversion. Anemia and diastolic
      blood pressure were significantly improved after successful conversion. The
      failed patients had a longer transplantation period (6.1 +/- 4.1 vs. 11.2 +/- 3.4
      yr, p < 0.05). Two of them (12.5%) developed bacteria pneumonia. Self-limited
      diarrhea developed in three patients (18.8%). CONCLUSION: We suggested that
      conversion from CNI to rapamycin was beneficial in some kidney transplant
      recipients with chronic allograft dysfunction.

PMID- 15740562
TI  - Airway cellular response to two different immunosuppressive regimens in lung
      transplant recipients.
AB  - A number of new immunosuppressive drugs have become available in transplant
      medicine. We investigated the effects of two different immunosuppressive
      protocols on bronchoalveolar lavage fluid cellular characteristics in 34 lung
      transplant recipients who were treated with anti-thymocyte globulin induction
      therapy, cyclosporine, azathioprine (AZA), and prednisolone (regimen I), compared
      with 17 recipients receiving basiliximab induction, tacrolimus, AZA, and
      prednisolone (regimen II). We performed bronchoalveolar lavages between 15 and 40
      d post-transplantation, in stable clinical condition and no acute rejection,
      cytomegalovirus, and/or respiratory tract infection. The regimen II treatment was
      associated with a significantly lower percentage lavage fluid lymphocytes than
      with regimen I. The CD4/CD8 ratio was significantly higher with regimen II than
      with regimen I: 1.56 (range 0.41-2.16) and 0.33 (0.04-0.95) respectively; p <
      0.001, mainly because of a lower percentage CD8(+) cells with regimen II: 25% (12
      51) vs. regimen I: 60% (34-77); p < 0.001. The percentage CD4(+) CD25(+) cells
      appeared lower with regimen II: 21% (10-88) vs. regimen I: 50% (0-87); p = 0.04.
      Overall survival was similar between the groups, whereas a beneficial trend in
      freedom of bronchiolitis obliterans syndrome was observed with regimen II. Airway
      lymphocyte subtypes are affected by the immunosuppressive protocol used. This
      observation should be taken into account when studying transplant recipients, and
      may contribute to our understanding of alloreactive airway disease.

PMID- 15740563
TI  - Gastrointestinal hemorrhage due to complicated gastroduodenal ulcer disease in
      liver transplant patients taking sirolimus.
AB  - Sirolimus is emerging as a popular immunosuppressive agent for patients
      undergoing solid organ and pancreatic cell transplantation. Here, we report the
      clinical courses of three patients receiving sirolimus who developed aggressive
      gastroduodenal ulcer disease. One patient died from massive gastrointestinal
      bleeding, and ulcers in the other two patients healed only after discontinuation
      of sirolimus. We propose that the mechanism underlying this severe ulcer
      diathesis, and poor ulcer healing, was linked to the well-known inhibitory
      effects of sirolimus on wound healing. We propose that sirolimus should be used
      carefully (or even withheld) in patients with known or previous ulcer disease,
      and further that it should be used prudently and/or in conjunction with
      aggressive prophylaxis therapy in those at risk for ulcer disease.

PMID- 15740564
TI  - Minimization of immunosuppression with thymoglobuline pre-treatment and HCV
      recurrence in liver transplantation.
AB  - Induction with thymoglobuline, a potent anti-thymocyte polyclonal antibody, has
      been recently reported to allow minimization of postoperative immunosuppression
      in organ transplantation. The relationship with recurrence of hepatitis C virus
      (HCV) after liver transplantation (LTx) has never been investigated. We report
      here on the outcome in 22 HCV+ patients receiving thymoglobuline pre-treatment
      and minimal immunosuppression after LTx. Patient survival and acute rejection
      rates were good, and remarkably low dosages and levels of immunosuppression were
      achieved with thymoglobuline, without exposing patients to an elevated risk of
      rejection. A progressive weaning of the primary immunosuppressor was also
      possible in the majority of patients without complications. The HCV recurrence
      rate was similar to what is reported in the literature, although lower HCV-RNA
      viral loads were obtained with thymoglobuline, with a mild histologic course.
      Although our results need to be validated in large cohort studies, our experience
      shows that minimization of immunosuppression with thymoglobuline is effective in
      protecting against rejection and demonstrated a positive impact on HCV recurrence
      that deserves further investigation.

PMID- 15740565
TI  - Limitations of glomerular filtration rate equations in the renal transplant
      patient.
AB  - This study aims to compare the performance of endogenous creatinine clearance
      (CL(cr)) and a number of published mathematical equations to calculate glomerular
      filtration rate (GFR) in renal transplant patients considering (99m)Tc DTPA
      isotope scan as the reference method. A total of 152 GFR were performed on 81
      renal transplant patients. Accuracy of each method was measured at different
      percentiles. The bias and precision of all the methods were then compared. A
      paired t-test was used to compare the performance of each calculation to the
      respective GFR measured by isotope study performed on the same day. In the total
      population, all calculated methods correlated significantly with the isotope
      results. Accuracies within specific ranges of the isotope GFR were limited in all
      equations (agreement with isotope result </=72% at 30% accuracy range in the
      total group). Within the limited accuracy, Edwards' equation (K.D. Edwards and
      H.M. Whyte, Australas Ann Med 1959; vol. 8: p. 218) had the least bias in the
      total population. Bjornsson (T.D. Bjornsson, Clin Pharmacokinet 1979; vol. 4: p.
      200) had the least bias in patients with GFR >/= 50 mL/min and Gates in patients
      with GFR < 50 mL/min. Salazar (D.E. Salazar and G.B. Corcoran, Am J Med 1988;
      vol. 84: p. 1053) had the least bias in patients with BMI above 30 kg/m(2) and
      the Davis equation (G.A. Davis and M.H. Chandler, Am J Health Syst Pharm 1996;
      vol. 53: p. 1028) in patients with BMI <25 kg/m(2). In all analyses, Nankivell
      (B.J. Nankivell, S.M. Gruenwald, R.D.M. Allen and J.R. Chapman, Transplantation
      1995; vol. 59: p. 1683) overestimated GFR by more than 80% and MDRD 1 and 2 in
      <10% of the time. The results demonstrate the inherited limitation in the
      currently available equations to calculate GFR in renal transplant patients.

PMID- 15740566
TI  - Should people who commit themselves to organ donation be granted preferred status
      to receive organ transplants?
AB  - Granting preferred status for transplantation to people who commit themselves to
      posthumous organ donation is an intriguing proposal designed to increase the pool
      of cadaveric organ donors. Under one version of this plan, all competent adults
      who had previously consented to having their organs removed and transplanted upon
      their deaths would be given priority to receive organs, should they ever need
      them, over potential recipients of equal need who had not agreed to donate. To
      see if this plan would be acceptable to the public, I contracted Harris
      Interactive to conduct a national telephone survey about this issue. One thousand
      fourteen adults living in the United States were queried. Fifty-three percent of
      the respondents thought that people who agree to donate their organs after death
      should be granted priority to receive cadaveric organ transplants over those who
      do not agree to donate. Only 30% of the respondents would definitely oppose this
      plan. These data suggest that a pilot study of preferred status should be
      considered.

PMID- 15740568
TI  - Mycophenolate mofetil vs. azathioprine is associated with decreased acute
      rejection, late acute rejection, and risk for cardiovascular death in renal
      transplant recipients with pre-transplant diabetes.
AB  - Outcomes specifically in mycophenolate mofetil (MMF)-treated diabetic renal
      transplant patients have not been previously reported. This study compared acute
      rejection (AR), late acute rejection (LAR), patient survival [and specifically
      death from cardiovascular (CV), infectious and malignant causes], incidence of
      post-transplant malignancies, and graft loss in MMF- or azathioprine (AZA)
      treated renal transplant patients with pre-transplant diabetes. Outcomes were
      compared between MMF- (n = 14 144) and AZA- (n = 3001) treated diabetic patients
      using the Scientific Registry of Transplant Recipients data on all U.S. adult
      renal transplants performed between 1995 and 2002. Statistical analyses included
      Kaplan-Meier survival analysis, Cox multivariable regression and chi-square
      tests. MMF patients had less AR compared with AZA-treated patients (23.5% vs.
      28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95%
      CI 0.44, 0.92; p = 0.02]. While time to any-cause death did not differ between
      the groups, MMF treatment was associated with a 20% decreased risk of CV death
      (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF
      patients also had a lower incidence of malignancies than AZA patients (2.2% vs.
      3.7%, p < 0.001). These results suggest treatment with MMF compared with
      treatment with AZA in diabetic transplant patients is associated with less AR,
      less risk of LAR, a decreased risk of CV death, and a lower incidence of
      malignancies.

PMID- 15740567
TI  - Cytomegalovirus prophylaxis with valganciclovir in African-American renal
      allograft recipients based on donor/recipient serostatus.
AB  - There is a paucity of data examining the efficacy of valganciclovir (VGC) for
      cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly
      with regard to utilization of a risk-stratified dosing regimen. Eighty adult
      African-American (AA) renal allograft recipients transplanted from November 3,
      2001 to May 28, 2003 and followed for 22 +/- 8 months received VGC once daily for
      90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high
      risk (D+/R-) received 900 mg (n = 12); moderate risk (D+/R+, D-/R+) received 450
      mg (n = 60); and low risk (D-/R-) received no prophylaxis (n = 8). Thymoglobulin
      or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and
      either tacrolimus or sirolimus for maintenance immunosuppression. Only six
      patients (7.5%) developed symptomatic CMV infection diagnosed by pp65
      antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%)
      group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to
      diagnosis. There were no cases of tissue-invasive disease, resistance to
      treatment, or recurrence. D+/R- serostatus was the only significant independent
      predictor for CMV infection using multivariate analysis (odds ratio 10.5; p =
      0.04). Thymoglobulin induction was not associated with CMV infection. None of 43
      patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six
      of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R
      serostatus provides safe and effective CMV prophylaxis in AA renal allograft
      recipients.

PMID- 15740569
TI  - Arterial reconstruction with donor iliac vessels during pancreas transplantation:
      an intraoperative approach to arterial injury or inadequate flow.
AB  - BACKGROUND: Outcome of pancreas transplantation (PTX) has improved because of use
      of novel immunosuppression and advances in surgical technique. It is not uncommon
      for severe atherosclerosis in patients with type 1 insulin-dependent diabetes
      mellitus or the presence of a previously transplanted organ to limit the options
      for vascular anastomosis. Herein we report the novel application of donor iliac
      arterial interposition grafts for arterial reconstruction in patients with severe
      iliac artery arteriosclerosis, and/or previous transplant who develop an arterial
      injury or stenosis during surgery. METHODS: In five patients undergoing PTX, the
      external iliac artery was severely atherosclerotic and/or occupied by a previous
      vascular anastomosis. In four of the five patients, an arterial intimal
      dissection became apparent. The external iliac artery was excised and
      reconstructed with donor iliac artery interposition graft (end-to-end
      anastomosis). Pancreas or kidney was engrafted onto this arterial interposition
      graft (end-to-side anastomosis). RESULTS: There was no operative morbidity
      related to this surgical approach. All grafts functioned well after
      transplantation. Distal lower extremities have no evidence of vascular
      insufficiency with mean follow-up of 26 months (7-45 months). CONCLUSION: This
      surgical technique is an acceptable option during PTX for the patient with severe
      iliac artery arteriosclerosis with intraoperative intimal dissection or stenosis,
      or perhaps those with challenging arterial access.

PMID- 15740570
TI  - Autosomal dominant cortical tremor, myoclonus and epilepsy: many syndromes, one
      phenotype.
AB  - The association of cortical tremor, myoclonus and epileptic seizures has been
      reported in many Japanese and European families with different acronyms. We
      reviewed the familial cases presenting the clinical picture of autosomal dominant
      cortical tremor, myoclonus and epilepsy and analysed the phenotypic differences
      between the pedigrees, according to the recent genetic acquisitions. We concluded
      that BAFME, FAME, FEME, FCTE and ADCME are the same clinical entity even if
      genetically heterogeneous, with Japanese families linked to 8q24 and Italian ones
      to 2p11.1-q12. A third locus could also be involved. Further studies should
      better clarify the electrophysiological features of this condition and identify
      the underlying molecular defects.

PMID- 15740571
TI  - Regional energetic dysfunction in hippocampal epilepsy.
AB  - OBJECTIVES: There is increasing evidence for a dysfunctional metabolic network in
      human mesial temporal lobe epilepsy (MTLE). To further describe this, we
      evaluated the bioenergetic status in unilateral MTLE inter-regionally and in
      relation to neuropathology. MATERIALS AND METHODS: We used whole brain high field
      (4 T) 31P MR spectroscopic imaging to determine in vivo PCr and ATP, studying
      n=22 patients (all candidates for hippocampal resection) and n=14 control
      volunteers. The degree of bioenergetic impairment was assessed by calculating the
      ratio of PCr to ATP. RESULTS: Compared to controls, patients demonstrated
      significant decreases in PCr/ATP from the ipsilateral amygdala and pes (0.84 +/-
      0.14, 0.87 +/- 0.10, respectively, patients vs 0.97 +/- 0.15, 0.98 +/- 0.16,
      controls). In patients, the ipsilateral thalamic energetics positively correlated
      with contralateral hippocampal energetics. In addition, the ipsilateral thalamic
      and striatal energetics negatively correlated with hippocampal total glial
      counts. CONCLUSIONS: These data are consistent with a view that in MTLE, the
      bilateral hippocampi, ipsilateral thalamus and striatum are linked in their
      energetic depression, possibly reflecting the propagation of seizures throughout
      the brain.

PMID- 15740572
TI  - An analysis of lifetime fractures in women with epilepsy.
AB  - OBJECTIVE: To clarify the relationship between fractures and antiepileptic drug
      (AED) use. METHODS: Menopausal women with epilepsy were interviewed at two
      clinics regarding site, year and circumstances of any fracture, duration of AED
      use and menopause. Fracture sites were analyzed according to AED use. RESULTS:
      Twenty-nine fractures occurred in 20 of the 50 interviewed subjects (mean age
      54). Nine occurred prior to AEDs; seven attributed to accident and two to
      clumsiness. Twenty occurred on AEDs; 10 attributed to clumsiness (most in the leg
      and foot), eight to seizure (most in the arm or hand) and two to accident.
      Duration of AED exposure was similar in both groups and in osteoporotic vs non
      osteoporotic sites. CONCLUSIONS: Epilepsy therapy may contribute more to the
      lifetime occurrence of fracture than seizures themselves. More screening for
      osteoporosis is required. While adjusting doses to prevent seizures, ongoing
      screening for neurotoxicity must be maintained in order to avoid fractures.

PMID- 15740573
TI  - Oxcarbazepine monotherapy in postherpetic neuralgia unresponsive to carbamazepine
      and gabapentin.
AB  - OBJECTIVES: We present the results of a preliminary, open-label trial to evaluate
      the efficacy and tolerability of oxcarbazepine in postherpetic neuralgia (PHN)
      unresponsive to treatment with antiepileptic drugs (carbamazepine and gabapentin)
      and local anesthetic blocks. MATERIALS AND METHODS: Twenty-four patients were
      treated with oxcarbazepine monotherapy for 8 weeks. Starting dose was 150 mg/day,
      subsequently increased by 150 mg/day every 2 days until a maintenance dose of 900
      mg/day. Pain was assessed using a visual analog scale (VAS). RESULTS: There was a
      significant decrease in the mean VAS score following 8 weeks of treatment
      (Delta=5.33; paired t-test: P <0.0001) compared with baseline. Oxcarbazepine was
      effective from the first week of treatment. There was a significant reduction in
      allodynia, leading to improvements in patients' functioning and quality of life.
      Oxcarbazepine was generally well tolerated. CONCLUSION: Oxcarbazepine appears to
      be a promising alternative monotherapeutic approach for patients affected by PHN.

PMID- 15740574
TI  - Headache and transient focal neurological symptoms during pregnancy, a
      prospective cohort.
AB  - OBJECTIVE: The main purpose of the present prospective study was to evaluate the
      course of migraine and non-migrainous headache during pregnancy and to estimate
      the occurrence of self-reported transient focal neurological symptoms. MATERIAL
      AND METHODS: In total 1631 (77%) pregnant women completed the study and were
      followed-up during pregnancy. The first questionnaire (Q1) was sent together with
      the appointment letter and delivered at the time of ultrasound screening. The
      second questionnaire (Q2), to be filled in during pregnancy, was delivered at the
      time of birth. Q1 and Q2 covered questions about headache, transient neurological
      symptoms, and other background and demographic data. Subjects reporting transient
      sensory, motor or visual disturbances were also interviewed by phone in order to
      achieve a more precise description of the symptoms. RESULTS: A total of 58%
      subjects with migraine reported not having migraine or no headache at all during
      pregnancy. Among individuals with non-migrainous headache 25% reported not having
      any headaches, while 1.9% of the subjects without headache experienced headache
      attacks during pregnancy that fulfilled the criteria for migraine. Individuals
      without headache or with non-migrainous headache reported significantly less
      sensory, motor and visual disturbances during pregnancy compared with migraine
      subjects. More than 60% of those with possible aura phenomenon were migraine
      patients, while symptoms of peripheral or non-neurological origin were more
      common among headache free or those with non-migrainous headache. CONCLUSION:
      Transient neurological symptoms were less common among individuals without or
      with non-migrainous headache compared with migraine. This may indicate that there
      is an increased susceptibility of unknown cause for these symptoms among migraine
      patients during pregnancy.

PMID- 15740575
TI  - Further considerations on the distribution of multiple sclerosis in Sweden.
AB  - OBJECTIVES: The geographic distribution of multiple sclerosis (MS) in Sweden over
      time was compared in order to analyze homogeneity. METHODS: The distribution of
      MS was compared among three nationwide resources: 1301 hospital cases 1925-1934;
      5425 deaths 1952-1992; and 11,371 disability pension recipients 1971-1994.
      RESULTS: Distributions by county (lan) were markedly non-homogenous, with
      greatest variations in the early prevalence series (16-232% of the national
      mean), less within the death data (75-170%), and least for the disability series
      (87-128%). Maximal rates for MS in the early prevalence series were found for the
      cluster of seven counties surrounding the two major lakes of south central
      Sweden, as well as for one region on the northern shore of the Bay of Bothnia,
      and another also off the Bay north of Stockholm. CONCLUSION: Though the
      epidemiologic sources are quite different, they are internally consistent and
      thus provide three consecutive cross-sectional views of the distribution over
      time. When considered together the data may be compatible with a thesis of the
      origin and spread of MS within Sweden from the south-central inland lake regions
      of the country. Such spread within a half century is too rapid for a genetic
      cause, including HLA patterns.

PMID- 15740576
TI  - Cyclosporine in the treatment of myasthenia gravis.
AB  - Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe
      generalized myasthenia gravis (MG) whose illness was not controlled by
      anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The
      efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ),
      which was obtained by comparing mean disability score (MDS) at the beginning of
      the treatment with the MDS at the end of the follow-up period. For the entire
      group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing
      individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate
      improvement, 20 (38%) showed remarkable improvement, and seven patients (14%)
      achieved complete remission. The most common side effects were rise of serum
      creatinine (seven), hypertension (two), gingival hyperplasia (two),
      hypertrichosis (six), myalgia (10), and 'flu-like' symptoms (10 patients). The
      results of this study suggest that CsA is efficacious and safe treatment in
      severe and resistant forms of MG.

PMID- 15740577
TI  - Lacunar stroke in patients with intermittent claudication.
AB  - OBJECTIVES: To compare the characteristics of lacunar stroke (LS) in patients
      with and without intermittent claudication. MATERIAL AND METHODS: Data of 484
      consecutive patients with LS were collected from a prospective hospital-based
      stroke registry in which 2500 patients are included. RESULTS: Of the 142 patients
      with ischemic stroke and intermittent claudication, 39 (27.5%) had LS (8% of all
      lacunes). In the multivariate analysis, small centrum ovale topography (odds
      ratio 7.35), carotid stenosis >50% (odds ratio 3.17), and absence of limitation
      at discharge (odds ratio 2.01) were independent variables significantly
      associated with LS in patients with intermittent claudication. CONCLUSION: Only
      8% of patients with LS had intermittent claudication. The short-term prognosis is
      good with a spontaneous early neurological recovery at discharge in 51.3% of
      patients. LS patients with intermittent claudication showed a striking similarity
      in risk factors and clinical syndromes in comparison with the LS patients without
      intermittent claudication.

PMID- 15740578
TI  - Clinical manifestations of chronic inflammatory demyelinating polyneuropathy with
      anti-cardiolipin antibodies.
AB  - OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an
      autoimmune syndrome where certain autoantibodies define clinicopathologic
      subgroups. In the present study, serum anti-cardiolipin antibodies (aCL) were
      evaluated. MATERIALS AND METHODS: We investigated aCL in sera from 21 patients
      diagnosed with CIDP in our hospital between 1991 and 2001. The four CIDP patients
      with aCL (aCL+) were compared with 17 patients without aCL (aCL-). RESULTS: All
      aCL+ patients displayed sensory-motor polyneuropathy, with severity and
      distribution of weakness resembling those in aCL- patients. Anti-nuclear antibody
      titer of aCL+ patients were significantly higher than those in aCL- patients.
      None of aCL+ patients presented clinical manifestations of primary anti
      phospholipid syndrome (APS), such as thromboses or recurrent abortion. Although
      the aCL+ patients were older and had more complications and more severe
      pathologic features than aCL- patients, they responded well to steroid pulse or
      intravenous immunoglobulin. CONCLUSION: The aCL in CIDP apparently differ from
      'autoimmune' aCL in APS, instead being among the autoantibodies pathologically
      involved in CIDP subgroups.

PMID- 15740579
TI  - Scoring alternatives for FIM in neurological disorders applying Rasch analysis.
AB  - OBJECTIVE: The Functional Independence Measure (FIM) is an internationally widely
      used outcome measure. The aim of this study was to evaluate the structural
      properties of FIM using the Rasch model, with regard to scoring within
      rehabilitation centres in Scandinavia. MATERIALS AND METHODS: FIM data from 1660
      patients with stroke, traumatic brain injury and spinal cord injury were
      analysed. The best models with respect to person separation were determined,
      together with person reliability, item separation, disordered categories,
      distance of more than 1.4 logits between categories and item fit to the model.
      RESULTS: Analysis showed disordering using seven categories in all three
      diagnoses. After collapsing of categories a four-category scale was the best
      solution. CONCLUSIONS: Decreasing the categories from seven to four may be one
      way of dealing with problems of disordered thresholds. Further studies are also
      needed in order to try the suggested scale in clinical settings and to compare it
      with the original FIM scale.

PMID- 15740580
TI  - Haplotype analysis of the DM1 locus in the Serbian population.
AB  - OBJECTIVES: Analysis of the CTG-repeat number and three biallelic markers, Alu(+/
      ), HinfI(+/-), and TaqI(+/-), in the DMPK gene in healthy and myotonic dystrophy
      type 1 (DM1) Serbian individuals. Also, the consideration of haplotypes in the
      light of the proposed models of CTG-repeat evolution and origin of the DM1
      mutation. MATERIALS AND METHODS: Markers were analyzed by PCR and haplotypes were
      obtained on 203 unrelated normal chromosomes and 24 unrelated DM1 chromosomes.
      RESULTS: A strong linkage disequilibrium was detected between the three biallelic
      markers alone (P <0.0001) and between distinct CTG-repeat size classes and
      reconstructed haplotypes. Greater than 98% of normal chromosomes contain (+++)
      and (- - -) haplotypes. The (+++) haplotype is the most common, while the (CTG)(9
      17) are the most frequent alleles. We found a complete association of (+++)
      haplotype with (CTG)(> or =18) and mutated alleles. CONCLUSIONS: (CTG)(9
      17)/(+++) haplotype is the ancestral haplotype and DM1 mutation occurred on
      (CTG)(18-35)/+++ chromosome.

PMID- 15740581
TI  - Embryonic and larval development of Thai Pangas (Pangasius sutchi Fowler, 1937).
AB  - The embryonic and larval development of Thai pangas was investigated during peak
      (May-July 1995) and late spawning (August-October 1995) periods. The fertilized
      eggs are adhesive and spherical with a yellowish or greenish-brown egg capsule.
      The yolk sac is yellowish-brown in color and 1.20-1.80 mm in diameter. Nine hours
      post-fertilization, the first cleavage stage, embryonic shield, head, tail
      region, neural grooves and somites were evident. The incubation period ranges
      from 24-36 h at a temperature of 20-30 degrees C. The newly hatched larvae are
      quite transparent and light yellowish in color with a body length of 2.98-3.10
      mm. Eye pigments appear and the heart starts to work within 12-14 h of hatching.
      In 1-day-old pro-larvae, the mouth becomes well developed; barbules are
      elongated, prominent and look like tiny threads. The yolk sac is fairly well
      absorbed and the palatine teeth are fully developed during the 3 day pro-larval
      stage. At the end of 12 days of larval development, the stomach becomes
      functional and aerial respiration starts. After 2 weeks, the young fry is well
      developed, and is of an adult appearance, that is, measuring up to 13.56 mm in
      length.

PMID- 15740582
TI  - Gonadal structure of the serial-sex changing gobiid fish Trimma okinawae.
AB  - In order to obtain basic information about the role played by endogenous sex
      hormones in bringing about sex changes in the serial-sex changing gobiid fish
      Trimma okinawae, the gonadal structure of male and female phases were observed
      histologically. Steroid-producing cells (SPC; Leydig cells in a testis) were
      observed ultrastructurally in the ovaries and testes of both female-phase and
      male-phase fish. In addition, gonadal expression of P450 cholesterol side-chain
      cleavage (scc) was examined immunohistochemically. Gonads of fish in female and
      male phases were observed to have both ovaries and testes simultaneously. Female
      phase fish had matured with many developed vitellogenic oocytes, while male-phase
      individuals had immature ovaries with many numbers of previtellogenic oocytes at
      the perinucleolus stage. Testes of fish in different sexual phases had active
      spermatogenic germ cells. Organellae of SPC in the ovaries of female-phase fish
      had active structures of steroid production. In contrast, SPC in the ovaries of
      male-phase fish did not show active structures of steroid production.
      Immunopositive reactions against the scc antibody in the ovaries of female-phase
      fish were very strong, but immunoreactions in the ovaries of male-phase fish were
      very weak. In the testis, moderate immunopositive signals were obtained from dual
      phase male/females.

PMID- 15740583
TI  - The testicular fatty acid binding protein PERF15 regulates the fate of germ cells
      in PERF15 transgenic mice.
AB  - The quality control of sperm is critical for efficient reproduction. In germ
      cells, cell death involves different processes to those in somatic cells, and in
      many cases, the trigger to induce cell death in deficient germ cells is still
      unclear. It is known that the fatty acid composition of sperm is related to
      fertility. Composition of the fatty acid of germ cells changes dynamically during
      spermatogenesis, and fatty acid binding protein (FABP) may be involved in these
      changes. In this study, we developed transgenic mice with a testicular germ-cell
      specific FABP (PERF15) transgene, whose expression was controlled by the Cre-LoxP
      site-specific recombination system. We also developed transgenic mice with the
      Cre gene under the control of the spermatocyte specific Pgk2 promoter. In double
      transgenic mice, following Cre-mediated recombination of the PERF15 containing
      transgene, PERF15 was strongly overexpressed. Its overexpression induced
      multinucleate symplasts to form, indicating programmed germ cell death occurred
      at the elongated spermatid stage. As a result, sperm harboring the transgene were
      significantly decreased, but the surviving sperm demonstrated higher fertility
      than natural sperm. Therefore, we conclude that PERF15 associate with the
      direction of germ cell fates and preserve the quality of sperm.

PMID- 15740584
TI  - Gamete fusion and cytokinesis preceding zygote establishment in the sexual
      process of Dictyostelium discoideum.
AB  - Cells of Dictyostelium discoideum become sexually mature under submerged and dark
      conditions, and fuse with opposite mating-type cells to form zygote giant cells,
      which gather surrounding cells and finally develop into dormant structures called
      macrocysts. In the present study, we found that the multinuclear fused cells
      formed during this process frequently underwent cytokinesis driven by random
      local movements. The split cells were capable of re-fusion, and repeated
      cytokinesis. These radical behaviors continued until the extensive cell
      aggregation started around the giant cells. Thus, gamete fusion and initiation of
      zygote development do not coincide in the mating of D. discoideum. Analyses by
      confocal microscopy and flow cytometry indicated that the cessation of the random
      movement followed pronuclear fusion, and that microtubule organizing centers
      (MTOC), abundant in the fused cells at the beginning, gradually decreased and
      only one of them remained within the developed macrocyst. Some of the genes known
      to control cell movement, such as rasGEFB and rasS, increased shortly before the
      cessation of repeated fusion-cytokinesis and initiation of phagocytosis. These
      results suggest that the sequential molecular events are necessary in D.
      discoideum after gamete fusion to establish a new individuality of zygotes.

PMID- 15740585
TI  - The mode and molecular mechanisms of the migration of presumptive PGC in the
      endoderm cell mass of Xenopus embryos.
AB  - We investigated the mode of migration of presumptive primordial germ cells (pPGC)
      in the endoderm cell mass of Xenopus embryos at stages 7-40. The molecules
      underlying the migration were also studied cytochemically and
      immunocytologically. By examining the relative positions of pPGC and somatic
      cells derived from the single, fluorescein-dextran lysine (FDL)-injected, germ
      plasm-bearing cells of stage 6 embryos, pPGC in embryos at stages 7-23 and those
      at stages later than 24 were assumed to passively and actively migrate in the
      endoderm cell mass, respectively. This assumption was supported by the
      observation that F-actin, essential for active cell migration, was recognized on
      pPGC of the latter stages, but never on those of the former ones. In addition,
      the molecule like CXC chemokine receptor 4 (CXCR4) found on directionally
      migrating PGC in mouse and zebrafish, probably Xenopus CXCR4 (xCXCR4), was
      detected on pPGC only at latter stages. Accordingly, F-actin and xCXCR4, and
      probably beta1-integrin and collagen type IV, which are indispensable for the
      formation of F-actin, are thought to be involved in the active migration of pPGC
      in the endoderm cell mass.

PMID- 15740586
TI  - Aerial migration of the Dictyostelium slug.
AB  - The Dictyostelium slug lays down curved marks in its slime sheath trail as it
      migrates across an agar substrate. These 'footprints' are caused by elevation of
      the slug anterior as it initiates a period of aerial migration and can be used as
      a measure of the slug's propensity for this behavior. A variety of factors have
      been found to affect the number of footprints created per distance migrated.
      Smaller slugs produce a higher incidence of footprints than larger slugs.
      Migration in the light and lower temperatures during migration increase footprint
      incidence. Activated charcoal reduces, while exogenous addition of ammonia
      increases, the incidence of footprints. Simulation of the three-dimensional (3D)
      environment of the soil suggests that aerial migration plays a role in the slug's
      movement through the cavities of its natural environment. A model proposes that
      aerial migration is initiated by a small group of continually changing prestalk
      cells that acts as a pacemaker and is moved around the circumference of the slug
      tip by the rotation of the prestalk cells. As this pacemaker reaches the upper
      surface of the slug it can initiate aerial migration.

PMID- 15740587
TI  - Expression patterns of S100A7 (psoriasin) and S100A9 (calgranulin-B) in
      keratinocyte differentiation.
AB  - S100 proteins are involved in many biological processes. S100A7 and S100A9 have
      been shown to be markedly upregulated both in ductal carcinoma in situ of the
      breast and in psoriasis. We have examined the relationship between keratinocyte
      differentiation and the expression of the two proteins. Using Western blot
      analysis and quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR), both S100A7 and S100A9 were shown to be induced in normal primary
      keratinocytes (HEKn), when differentiation was promoted by high extracellular
      calcium, loss of contact with extracellular matrix and confluent conditions, as
      previously reported for S100A7 in mammary epithelial cells. Differentiation was
      confirmed by using RT-PCR for the differentiation marker keratin-1. Using
      immunohistochemistry with monoclonal antibodies, we compared the expression of
      the two proteins in a spectrum of conditions of dysregulated keratinocyte
      differentiation. We found a strikingly similar distribution of the proteins.
      Their expression correlated with the degree of keratinocyte differentiation. They
      were both absent in undifferentiated basalioma and strongly expressed in
      carcinoma in situ, as well as in keratoacanthoma and differentiated squamous cell
      carcinoma. In normal epithelium, they were expressed in the superficial,
      differentiated region of the epithelium rather than in the basal region. These
      findings support the hypothesis that these two S100 proteins are involved in
      keratinocyte differentiation.

PMID- 15740588
TI  - Inhibition of scratching behaviour caused by contact dermatitis in histidine
      decarboxylase gene knockout mice.
AB  - A neuronal system dedicated to itch consists of primary afferent and
      spinothalamic projection neurons. Histamine is thought to be one of the main
      mediators for the transmission of itch sensation. However, there are little
      available information on the role of histamine in scratching behaviour and
      sensory transmission of atopic dermatitis and chronic eczema. In the present
      study, the role of histamine in scratching behaviour and neural conduction of
      sensation in the chronic eczema model was investigated by using l-histidine
      decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact
      dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on
      a hind paw of HDC (+/+) and HDC (-/-) mice for 2 months. The observation of
      scratching behaviour and the hot-plate test were performed in both mice.
      Histological studies were performed in the skin and spinal cord tissues.
      Histological examination revealed that both HDC (+/+) and HDC (-/-) mice
      displayed the similar extent of inflammatory cell infiltration, hyperplastic
      epidermis and newly spreading of neuronal processes in the skin tissue.
      Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was
      barely observed in HDC (-/-) mice. The expression of c-Fos was specifically
      upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following
      repeated DCP application. Scratching behaviour in chronic contact dermatitis in
      mice was thought mainly mediated with histamine. The afferent pathway of
      sensation in chronic contact dermatitis model may connect with the central
      nervous system through lamina I of the spinal dorsal horn.

PMID- 15740589
TI  - Evaluation of a sunscreen photoprotective effect by ascorbic acid assessment in
      human dermis using microdialysis and gas chromatography mass spectrometry.
AB  - Ultraviolet irradiation causes adverse effects like sunburn, photosensitivity
      reactions or immunologic suppression. The aim of this study was to evaluate the
      photo-protective outcome of a sunscreen cream (SPF8) by the determination of
      erythema indexes and the assessment of ascorbic acid and its metabolites in human
      dermis. These substances were used as markers of oxidative effect. Eight healthy
      female subjects were enrolled in this study. Two abdominal areas were exposed to
      solar simulated irradiation with three minimal erythema dose, one with SPF8
      application and the other site without SPF8 application. Two other areas were
      used as control, one without SPF8 application and the other site after SPF8
      application. Ascorbic acid and its metabolites (dehydroascorbic acid, threonic
      acid, oxalic acid and xylose) were collected from human dermis by microdialysis
      and assessed by gas chromatography mass spectrometry. Irradiated site without
      sunscreen application had significantly demonstrated lower dermis ascorbic acid
      concentrations and a higher erythema index than the three other sites (P < 0.05).
      Threonic acid, oxalic acid and xylose dermis concentrations were significantly
      higher in site III than in the control site I (P < 0.05). The protected
      irradiated site did not show erythema formation and there was stability of
      ascorbic acid dermis concentrations with non-variation in its metabolites. The
      assessment of ascorbic acid and its metabolites in human dermis could be an
      efficient tool to demonstrate the oxidative process and consequently to control
      the efficiency of sunscreen creams against undesirable UV effects.

PMID- 15740590
TI  - In vivo and in vitro evidence for autocrine DCoH/HNF-1alpha transcription of
      albumin in the human epidermis.
AB  - The presence of albumin in the human epidermis has been reported more than a
      decade ago, but until now, it was assumed that this protein is synthesized in the
      liver and transported to the avascular skin. To our knowledge, transcription of
      albumin in the human epidermis was never considered. In this report, we present
      for the first time evidence for autocrine synthesis of albumin in the human
      epidermis in keratinocytes in situ and in vitro. Using double immunofluorescence
      labelling, we identified that albumin colocalized together with its transcription
      factor PCD/DCoH/HNF-1alpha in suprabasal keratinocytes in human full-thickness
      skin sections and in keratinocytes cultured in serum-free medium. Moreover,
      albumin and HNF-1alpha protein expression was confirmed by Western blotting in
      undifferentiated and differentiated keratinocytes as well as in human epidermal
      suction blister roof extracts. Reverse-transcriptase polymerase chain reaction
      analysis from human epidermal keratinocytes and epidermal suction blister roofs
      revealed the transcription of albumin. Using in vivo fluorescence excitation
      spectroscopy at the surface of human skin, we confirmed albumin as a major
      constituent yielding a lambda(max) at 295 nm, which was assigned to the single
      tryptophan 214 fluorophore in this protein. This in vivo result is in agreement
      with albumin concentrations of 10(-3) M, underlining the importance of this
      protein in epidermal homeostasis.

PMID- 15740591
TI  - Zeta-chain-associated protein-70 molecule is essential for the proliferation and
      the final maturation of dendritic epidermal T cells.
AB  - Adult murine epidermis contains members of the epithelial gammadelta T-cell
      family called dendritic epidermal T cells (DETCs). Their development and
      maturation have been the subjects of investigations, but the details are still
      unclear. T-cell receptor (TCR) zeta-chain-associated protein-70 (ZAP-70), one of
      the protein tyrosine kinases required for TCR signaling, plays a pivotal role in
      the development of alphabeta T cells. In mice lacking ZAP-70, thymic development
      of alphabeta T cells was completely arrested at the immature CD4(+)CD8(+)
      TCR(low) stage. Here, we examined whether or not the development and maturation
      of DETCs were altered in ZAP-70-deficient mice. Immunohistochemical analyses of
      epidermal sheets revealed that the number of DETCs was reduced and their
      characteristic dendrites were lost or markedly shortened in ZAP-70(-/-) mice. In
      flow cytometric analyses, the expression levels of gammadelta TCR and Thy-1.2 on
      the ZAP-70(-/-) DETCs were lower than those on ZAP-70(+/-) DETCs. The expression
      of a very early activation antigen, CD69, was not detected on ZAP-70(-/-) DETCs,
      whereas CD69 was expressed on ZAP-70(+/-) DETCs. Furthermore, ZAP-70(-/-) DETCs
      showed markedly reduced proliferation and no IL-2 gene expression in response to
      anti-CD3epsilon or concanavalin A stimulation. These results suggest that ZAP-70
      is essential for TCR signaling which induces the proliferation and the final
      maturation of DETCs in the epidermis.

PMID- 15740592
TI  - Polyunsaturated fatty acids partially reproduce the role of melanocytes in the
      epidermal melanin unit.
AB  - The incidence rate of melanoma is higher in fair-skinned than in dark-skinned
      individuals. In negroid skin there is more eumelanin which is present in all skin
      layers and fewer polyunsaturated fatty acids (PUFA) than in caucasoid skin. The
      western diet, which is rich in omega-6 polyunsaturated fatty acids, is associated
      with more proneness to cancer including cutaneous melanoma. To study the
      respective influence of omega-6 PUFA and low phototype melanocytes on redox
      status -basal and following UV irradiation-, we used epidermal reconstructs. The
      addition of polyunsaturated fatty acids as well as the presence of low phototype
      melanocytes affected basal status similarly except for catalase activity, which
      decreased significantly in polyunsaturated fatty acid-supplemented reconstructs.
      Following UV, polyunsaturated fatty acids and low phototype melanocytes increased
      lipid and protein oxidative damage without affecting direct DNA damage. However,
      polyunsaturated fatty acids increased epidermal apoptosis whereas low phototype
      melanocytes decreased it. Since our data suggest that an omega-6 PUFA rich-diet
      may increase oxidative damage in melanocytes without inducing apoptosis, the long
      term net outcome could be cumulated mutations and an increased risk of skin
      cancer, especially melanoma.

PMID- 15740593
TI  - FGF-2 blocks TGF-beta1-mediated suppression of Bcl-2 in normal melanocytes.
AB  - Normal melanocytes require growth support provided by the adjacent basement
      membrane. In contrast, nevus cells and melanoma cells survive in the dermis, and
      in vitro on a soft collagen gel. Transforming growth factor-beta1 (TGF-beta1)
      produced by melanocytes themselves induces apoptosis in normal melanocytes
      cultured on collagen gel, an effect that can be counteracted by fibroblast growth
      factor-2 (FGF-2). The purpose of this study was to investigate the mechanisms by
      which FGF-2 counteracts the apoptotic signals from TGF-beta1 in melanocytes
      cultured on collagen gel. We report that FGF-2 did not interfere with the signal
      transduction from the TGF-beta1 receptors to SMAD2/3 proteins. Instead, TGF-beta1
      decreased the level of Bcl-2 in normal melanocytes cultured on collagen gel, and
      FGF-2 reversed the TGF-beta1-mediated reduction in the level of Bcl-2. In nevus
      and melanoma cells, TGF-beta1 was unable to induce a decrease in the level of Bcl
      2, and treatment with FGF-2 did not cause an increase in the level of Bcl-2 in
      nevus or melanoma cells. In conclusion, our results suggest that a reduction in
      the level of the anti-apoptotic Bcl-2 is involved in the execution of apoptosis
      induced by TGF-beta1 in normal melanocytes cultured on collagen gel and that FGF
      2 can prevent TGF-beta1 from causing this reduction.

PMID- 15740594
TI  - Apoptosis of the dermal papilla cells of hair follicle associated with the
      expression of gene HSPCO16 in vitro.
AB  - The epithelial-mesenchymal interactions have an important role in the
      folliculomorphogenesis and mature hair follicle cycling. The dermal papilla, a
      dense aggregate of specialized dermis-derived stromal cells located at the bottom
      of the hair follicle, is a major component of hair, which signals the follicular
      epithelial cells to prolong the hair growth process. However, to date, little is
      known about the significance of the specific gene(s) expression in the dermal
      papilla cells with regard to their aggregative behaviour and hair cycling. In our
      previous study, the differentially gene-expressed cDNAs library had been
      determined by means of suppression subtractive hybridization technique between
      the aggregated human dermal papilla cells and control cells. Among those cDNAs
      library, the haematopoietic stem/progenitor cell (HSPC)-related gene HSPC016 was
      found. In this study, the gene HSPC016 was confirmed to express in the human
      dermal papilla cells by means of in situ hybridization and reverse transcriptase
      polymerase chain reaction. In order to rudimentarily elucidate its biological
      function, a recombinant eucaryotic expressing plasmid pcDNA3.1(+)/HSPC016 was
      constructed and was transfected into the human dermal papilla cells and 3T3
      fibroblast cells by means of Nucleofector(TM) technique (Amaxa, Cologne,
      Germany). Terminal deoxynucleotidyl transferase-mediated d-UTP nick end Labelling
      (TUNEL) assay showed that the expression of gene HSPCO16 resulted in the
      apoptosis of these cells, which suggested that the apoptosis of dermal papilla
      cells might be associated with the expression of gene HSPC016 in vitro.

PMID- 15740597
TI  - How best to fight that nasty itch - from new insights into the
      neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to
      novel therapeutic approaches.
AB  - While the enormous clinical and psychosocial importance of pruritus in many areas
      of medicine and the detrimental effects of chronic 'itch' on the quality of life
      of an affected individual are widely appreciated, the complexity of this
      sensation is still often grossly underestimated. The current Controversies
      feature highlights this complexity by portraying pruritus as a truly
      interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology,
      neuropharmacology, protease research, internal medicine, and dermatology, which
      is combated most successfully if one keeps the multilayered nature of 'itch' in
      mind and adopts a holistic treatment approach - beyond the customary, frequently
      frustrane monotherapy with histamine receptor antagonists. In view of the often
      unsatisfactory, unidimensional, and altogether rather crude standard instruments
      for pruritus management that we still tend to use in clinical practice today, an
      interdisciplinary team of pruritus experts here critically examines recent
      progress in pruritus research that future itch management must take into
      consideration. Focusing on new insights into the neuroimmunological,
      neuroendocrine, and neurophysiological bases of pruritus, and discussing
      available neuropharmacological tools, specific research avenues are highlighted,
      whose pursuit promises to lead to novel, and hopefully more effective, forms of
      pruritus management.

PMID- 15740595
TI  - Bactericidal activity of flucloxacillin against Staphylococcus aureus in primary
      keratinocyte cultures of lesional and unaffected skin of patients suffering from
      atopic dermatitis.
AB  - More than 90% of patients with atopic dermatitis (AD) are colonized by
      Staphylococcus aureus. Due to prevalent multi-resistant strains, it is highly
      difficult to eliminate S. aureus contamination of primary cell cultures of human
      AD skin by means of the antibiotics commonly used in cell culture. Therefore, an
      anti-staphylococcal treatment was investigated by which sterile proliferating
      keratinocyte cultures are attained from lesional and unaffected skin of AD
      patients by applying flucloxacillin, which in general is systemically used in
      vivo. The treatment with 1% flucloxacillin for 20 min included both colonized
      skin samples and contaminated primary cell cultures. In the case of persistent
      contamination, this step was repeated as often as required until complete
      decontamination without any cytotoxic indications was achieved. Antibacterial
      treatment with flucloxacillin permitted the cultivation of sterile, vital, and
      proliferating primary cultures of human skin keratinocytes from lesional and
      unaffected skin of AD patients with S. aureus colonization. The method increased
      the success rate of isolation of AD keratinocytes from 30 to 90%, representing on
      average 3 vs. 9 successfully isolated, sterile and proliferating cultures out of
      10 contaminated skin biopsies, which is comparable to normal human keratinocyte
      isolation rates.

PMID- 15740610
TI  - Human desmoid fibroblasts: matrix metalloproteinases, their inhibitors and
      modulation by Toremifene.
AB  - BACKGROUND: Desmoid tumour is a benign, non metastasising neoplasm characterised
      by an elevated deposition of organic macromolecules in the extracellular matrix
      (ECM). The matrix metalloproteinases (MMPs) are a family of zinc-dependent
      proteinases involved in the degradation of ECM macromolecules. The MMPs and their
      natural inhibitors (TIMPs) have been implicated in tumour growth, invasion and
      metastasis. In this study we provide evidence that the in vitro cultured cell
      line from desmoid tumour accumulates more collagen fibres in the ECM than healthy
      fibroblasts. METHODS: We investigated collagen accumulation by 3H-thymidine
      incorporation, MMP expression by substrate gel zymography and TIMP expression by
      Western blot analysis. RESULTS: Desmoid fibroblasts showed a reduction in MMP
      activity and an increase of type I and III collagen and TIMPs compared to normal
      fibroblasts. CONCLUSION: The increase in collagen in desmoid fibroblasts was due
      to inhibited collagen degradation (reduction of MMP activity) rather than to
      increased collagen synthesis. Adding toremifene, an anti-estrogen
      triphenylethylene derivate, to desmoid fibroblasts reduced collagen accumulation
      by decreasing mRNA expression and increasing collagen degradation.

PMID- 15740612
TI  - htSNPer1.0: software for haplotype block partition and htSNPs selection.
AB  - BACKGROUND: There is recently great interest in haplotype block structure and
      haplotype tagging SNPs (htSNPs) in the human genome for its implication on htSNPs
      based association mapping strategy for complex disease. Different definitions
      have been used to characterize the haplotype block structure in the human genome,
      and several different performance criteria and algorithms have been suggested on
      htSNPs selection. RESULTS: A heuristic algorithm, generalized branch-and-bound
      algorithm, is applied to the searching of minimal set of haplotype tagging SNPs
      (htSNPs) according to different htSNPs performance criteria. We develop a
      software htSNPer1.0 to implement the algorithm, and integrate three htSNPs
      performance criteria and four haplotype block definitions for haplotype block
      partitioning. It is a software with powerful Graphical User Interface (GUI),
      which can be used to characterize the haplotype block structure and select htSNPs
      in the candidate gene or interested genomic regions. It can find the global
      optimization with only a fraction of the computing time consumed by exhaustive
      searching algorithm. CONCLUSION: htSNPer1.0 allows molecular geneticists to
      perform haplotype block analysis and htSNPs selection using different definitions
      and performance criteria. The software is a powerful tool for those focusing on
      association mapping based on strategy of haplotype block and htSNPs.

PMID- 15740611
TI  - Genetic linkage analysis supports the presence of two susceptibility loci for
      alcoholism and heavy drinking on chromosome 1p22.1-11.2 and 1q21.3-24.2.
AB  - BACKGROUND: In order to confirm a previous finding of linkage to alcoholism on
      chromosome 1 we have carried out a genetic linkage study. METHODS: DNA from
      eighteen families, densely affected by alcoholism, was used to genotype a set of
      polymorphic microsatellite markers at loci approximately 10 centimorgans apart
      spanning the short arm and part of the long arm of chromosome 1. Linkage analyses
      were performed using the classical lod score and a model-free method. Three
      different definitions of affection status were defined, these were 1. Heavy
      Drinking (HD) where affected subjects drank more than the Royal College of
      Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for
      alcoholism (RDCA) 3. Alcohol Dependence Syndrome (ADS) as defined by Edwards and
      Gross (1976) and now incorporated into ICD10 and DSMIV. RESULTS: Linkage analyses
      with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1
      11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at
      D1S1588 (1p22.1) for the RDCA definition of alcoholism. Another lod of 1.8 was
      found with D1S1653 in the region 1q21.3-24.2 using the HD affection model.
      CONCLUSION: These results both support the presence of linkage in the 1p22.1-11.2
      region which was previously implicated by the USA Collaborative Study of the
      Genetics of Alcoholism (COGA) study and also suggest the presence of another
      susceptibility locus at 1q21.3-24.2.

PMID- 15740613
TI  - The prevalence of dental erosion in Nigerian patients with gastro-oesophageal
      reflux disease.
AB  - BACKGROUND: In various people of the Western world, gastro-oesophageal reflux
      (GOR) has been reported to be a common problem. Various studies have also
      assessed the relationship between GOR and dental erosion. The authors are not
      aware of such studies in Nigerians. It is therefore the aims of the present study
      to estimate the prevalence of GOR; to estimate the prevalence of dental erosion
      in patients with GORD; to document the oral findings in patients diagnosed with
      GORD and to compare these findings with previous studies elsewhere. METHODS: A
      total of 225 subjects comprising of 100 volunteers and 125 patients diagnosed
      with GORD were involved in this study. History of gastric juice regurgitation and
      heartburn were recorded. Oral examination to quantify loss of tooth structure was
      done using the tooth wear index (TWI) designed by Smith and Knight (1984).
      RESULTS: Twenty patients with GORD presented with dental erosion in the maxillary
      anterior teeth with TWI scores ranging from 1-3. The prevalence of erosion was
      found to be statistically significant between GORD patients (16%) and control
      (5%) (p < 0.05), but not significant between endoscopic diagnostic groups (p >
      0.05). CONCLUSION: The present study supports the consideration of dental erosion
      as the extra-oesophageal manifestation of GORD. However the association between
      GORD and burning mouth sensation needs more investigation.

PMID- 15740614
TI  - The use of edge-betweenness clustering to investigate biological function in
      protein interaction networks.
AB  - BACKGROUND: This paper describes an automated method for finding clusters of
      interconnected proteins in protein interaction networks and retrieving protein
      annotations associated with these clusters. RESULTS: Protein interaction graphs
      were separated into subgraphs of interconnected proteins, using the JUNG
      implementation of Girvan and Newman's Edge-Betweenness algorithm. Functions were
      sought for these subgraphs by detecting significant correlations with the
      distribution of Gene Ontology terms which had been used to annotate the proteins
      within each cluster. The method was implemented using freely available software
      (JUNG and the R statistical package). Protein clusters with significant
      correlations to functional annotations could be identified and included groups of
      proteins know to cooperate in cell metabolism. The method appears to be resilient
      against the presence of false positive interactions. CONCLUSION: This method
      provides a useful tool for rapid screening of small to medium size protein
      interaction datasets.

PMID- 15740615
TI  - A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture
      in formins from Dictyostelium, fungi and metazoa.
AB  - BACKGROUND: Formins are multidomain proteins defined by a conserved FH2 (formin
      homology 2) domain with actin nucleation activity preceded by a proline-rich FH1
      (formin homology 1) domain. Formins act as profilin-modulated processive actin
      nucleators conserved throughout a wide range of eukaryotes. RESULTS: We present a
      detailed sequence analysis of the 10 formins (ForA to J) identified in the genome
      of the social amoeba Dictyostelium discoideum. With the exception of ForI and
      ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where
      DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding
      domain/formin homology 3 domain that we propose to represent a single domain.
      ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and
      ForA, E and J have additional unique domains. To establish the relationship
      between formins of Dictyostelium and other organisms we constructed a
      phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used
      to study the expression pattern of formin genes. Expression of forC, D, I and J
      increased during transition to multi-cellular stages, while the rest of genes
      displayed less marked developmental variations. During sexual development,
      expression of forH and forI displayed a significant increase in fusion competent
      cells. CONCLUSION: Our analysis allows some preliminary insight into the
      functionality of Dictyostelium formins: all isoforms might display actin
      nucleation activity and, with the exception of ForI, might also be susceptible to
      autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2
      DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for
      which we propose the denomination of conventional formins, and implies a common
      regulatory mechanism.

PMID- 15740616
TI  - Analysis of leukocyte membrane protein interactions using protein microarrays.
AB  - BACKGROUND: Protein microarrays represent an emerging class of proteomic tools to
      investigate multiple protein-protein interactions in parallel. A sufficient
      proportion of immobilized proteins must maintain an active conformation and an
      orientation that allows for the sensitive and specific detection of antibody and
      ligand binding. In order to establish protein array technology for the
      characterization of the weak interactions between leukocyte membrane proteins, we
      selected the human leukocyte membrane protein CD200 (OX2) and its cell surface
      receptor (hCD200R) as a model system. As antibody-antigen reactions are generally
      of higher affinity than receptor-ligand binding, we first analyzed the reactivity
      of monoclonal antibodies (mAb) to normal and mutant forms of immobilized CD200R.
      RESULTS: Fluorescently labelled mAb DX147, DX136 and OX108 were specifically
      reactive with immobilized recombinant hCD200R extracellular region, over a range
      of 0.1-40 microg ml(-1) corresponding to a limit of sensitivity of 0.01-0.05
      femtomol per spot. Orientating hCD200R using capture antibodies, showed that
      DX147 reacts with an epitope spatially distinct from the more closely related
      DX136 and OX108 epitopes. A panel of soluble recombinant proteins with mutations
      in hCD200R domain 1 produced by transiently transfected cells, was arrayed
      directly without purification and screened for binding to the three mAb. Several
      showed decreased binding to the blocking mAb DX136 and OX108, suggesting close
      proximity of these epitopes to the CD200 binding site. Binding of hCD200 to
      directly immobilized rat, mouse, and hCD200R was achieved with multimeric
      ligands, in the form of biotinylated-hCD200 coupled to FITC-labelled avidin
      coated beads. CONCLUSION: We have achieved sensitive, specific and reproducible
      detection of immobilized CD200R with different antibodies and mapped antigenic
      epitopes for two mAb in the vicinity of the ligand binding site using protein
      microarrays. We also detected CD200 binding to its receptor, a low affinity
      interaction, using beads presenting multivalent ligands. Our results demonstrate
      the quantitative aspects of protein arrays and their potential use in detecting
      simultaneously multiple protein-protein interactions and in particular the weak
      interactions found between leukocyte membrane proteins.

PMID- 15740617
TI  - Salivary changes and dental caries as potential oral markers of autoimmune
      salivary gland dysfunction in primary Sjogren's syndrome.
AB  - BACKGROUND: the classification criteria for primary Sjogren's syndrome (pSS)
      include a number of oral components. In this study we evaluated if salivary flow
      and composition as well as dental caries are oral markers of disease severity in
      pSS. METHODS: in 20 patients fulfilling the American-European Consensus criteria
      for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates
      and composition, measures of oral dryness, scores of decayed, missing and filled
      tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were
      examined. RESULTS: in pSS, salivary flow rates, pH, and buffer capacities were
      lower, and DMFS, salivary sodium and chloride concentrations higher than in the
      healthy controls. DMFS also correlated inversely to salivary flow rates and
      positively to oral dryness. Apart from slightly increased gingival index, and
      more frequent dental visits in pSS, the periodontal condition, oral hygiene or
      sugar intake did not differ between these two groups. In pSS, findings were
      correlated to labial salivary gland focus score (FS) and presence of serum
      autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the
      highest FS (>2) also had the highest salivary sodium and chloride concentrations,
      the lowest salivary phosphate concentrations, lowest salivary flow rates, and
      highest DMFS compared to those with normal salivary concentrations of sodium and
      chloride at a given flow rate. CONCLUSION: the salivary changes observed in some
      pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar
      transport mechanisms, despite low salivary secretion. Our results suggest that
      changes in salivary flow and composition as well as dental caries may serve as
      potential markers of the extent of autoimmune-mediated salivary gland dysfunction
      in pSS. The study also indicates that the ductal epithelium is functionally
      affected in some pSS patients, which calls for future pathophysiological studies
      on the mechanisms underlying this impaired salt reabsorption.

PMID- 15740618
TI  - Asymmetry in host and parasitoid diffuse coevolution: when the red queen has to
      keep a finger in more than one pie.
AB  - BACKGROUND: Coevolution between pairs of antagonistic species is generally
      considered an endless "arms race" between attack and defense traits to counteract
      the adaptive responses of the other species. PRESENTATION OF THE HYPOTHESIS: When
      more than two species are involved, diffuse coevolution of hosts and parasitoids
      could be asymmetric because consumers can choose their prey whereas preys do not
      choose their predator. This asymmetry may lead to differences in the rate of
      evolution of the antagonistic species in response to selection. The more long
      standing the coevolution of a given pair of antagonistic populations, the higher
      should be the fitness advantage for the consumer. Therefore, the main prediction
      of the hypothesis is that the consumer trophic level is more likely to win the
      coevolution race. TESTING THE HYPOTHESIS: We propose testing the asymmetry
      hypothesis by focusing on the tritrophic system plant/aphid/aphid parasitoid. The
      analysis of the genetic variability in the virulence of several parasitoid
      populations and in the defenses of several aphid species or several clones of the
      same aphid species could be compared. Moreover, the analysis of the neutral
      population genetic structure of the parasitoid as a function of the aphid host,
      the plant host and geographic isolation may complement the detection of
      differences between host and parasitoid trophic specialization. IMPLICATIONS OF
      THE HYPOTHESIS: Genetic structures induced by the arms race between antagonistic
      species may be disturbed by asymmetry in coevolution, producing neither rare
      genotype advantages nor coevolutionary hotspots. Thus this hypothesis profoundly
      changes our understanding of coevolution and may have important implications in
      terms of pest management.

PMID- 15740619
TI  - The Future of Smallpox Vaccination: is MVA the key?
AB  - Eradication of the smallpox virus through extensive global vaccination efforts
      has resulted in one of the most important breakthroughs in medical history,
      saving countless lives from the severe morbidity and mortality that is associated
      with this disease. Although smallpox is now extinct in nature, laboratory stocks
      of this virus still remain and the subject of smallpox vaccination has gained
      renewed attention due to the potential risk that smallpox may be used as a
      biological weapon by terrorists or rogue states. Despite having the longest
      history of any modern vaccine, there is still much to be learned about smallpox
      vaccination and the correlates of protection remain to be formally defined. This
      Commentary will discuss the strengths and weaknesses of traditional smallpox
      vaccination in comparison with immunization using modified vaccinia virus Ankura
      (MVA), a non-replicating virus with a strong safety record but weakened
      immunogenicity.

PMID- 15740621
TI  - A wireless body area network of intelligent motion sensors for computer assisted
      physical rehabilitation.
AB  - BACKGROUND: Recent technological advances in integrated circuits, wireless
      communications, and physiological sensing allow miniature, lightweight, ultra-low
      power, intelligent monitoring devices. A number of these devices can be
      integrated into a Wireless Body Area Network (WBAN), a new enabling technology
      for health monitoring. METHODS: Using off-the-shelf wireless sensors we designed
      a prototype WBAN which features a standard ZigBee compliant radio and a common
      set of physiological, kinetic, and environmental sensors. RESULTS: We introduce a
      multi-tier telemedicine system and describe how we optimized our prototype WBAN
      implementation for computer-assisted physical rehabilitation applications and
      ambulatory monitoring. The system performs real-time analysis of sensors' data,
      provides guidance and feedback to the user, and can generate warnings based on
      the user's state, level of activity, and environmental conditions. In addition,
      all recorded information can be transferred to medical servers via the Internet
      and seamlessly integrated into the user's electronic medical record and research
      databases. CONCLUSION: WBANs promise inexpensive, unobtrusive, and unsupervised
      ambulatory monitoring during normal daily activities for prolonged periods of
      time. To make this technology ubiquitous and affordable, a number of challenging
      issues should be resolved, such as system design, configuration and
      customization, seamless integration, standardization, further utilization of
      common off-the-shelf components, security and privacy, and social issues.

PMID- 15740620
TI  - Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary
      collateral circulation and atherosclerotic plaque.
AB  - This review article is aimed at comparing the results of histopathological and
      clinical imaging studies to assess coronary collateral circulation in humans. The
      role of collaterals, as emerging from morphological studies in both normal and
      atherosclerotic coronary vessels, is described; in addition, present role and
      future perpectives of echocardiographic techniques in assessing collateral
      circulation are briefly summarized.

PMID- 15740622
TI  - Design considerations for a wearable monitor to measure finger posture.
AB  - BACKGROUND: Objective measures of hand function as individuals participate in
      home and community activities are needed in order to better plan and evaluate
      rehabilitation treatments. Traditional measures collected in the clinical setting
      are often not reflective of actual functional performance. Recent advances in
      technology, however, enable the development of a lightweight, comfortable data
      collection monitor to measure hand kinematics. METHODS: This paper presents the
      design analysis of a wearable sensor glove with a specific focus on the sensors
      selected to measure bend. The most important requirement for the glove is easy
      donning and removal for individuals with significantly reduced range of motion in
      the hands and fingers. Additional requirements include comfort and durability,
      cost effectiveness, and measurement repeatability. These requirements eliminate
      existing measurement gloves from consideration. Glove construction is introduced,
      and the sensor selection and glove evaluation process are presented. RESULTS:
      Evaluation of commercial bend sensors shows that although most are not
      appropriate for repeatable measurements of finger flexion, one has been
      successfully identified. A case study for sensor glove repeatability using the
      final glove configuration and sensors does show a high degree of repeatability in
      both the gripped and flat hand positions (average coefficient of variability =
      2.96% and 0.10%, respectively). CONCLUSION: Measuring functional outcomes in a
      portable manner can provide a wealth of information important to clinicians for
      the evaluation and treatment of movement disorders in the hand and fingers. This
      device is an important step in that direction as both a research and an
      evaluation method.

PMID- 15740623
TI  - Initial development and testing of a novel foam-based pressure sensor for
      wearable sensing.
AB  - BACKGROUND: This paper provides an overview of initial research conducted in the
      development of pressure-sensitive foam and its application in wearable sensing.
      The foam sensor is composed of polypyrrole-coated polyurethane foam, which
      exhibits a piezo-resistive reaction when exposed to electrical current. The use
      of this polymer-coated foam is attractive for wearable sensing due to the
      sensor's retention of desirable mechanical properties similar to those exhibited
      by textile structures. METHODS: The development of the foam sensor is described,
      as well as the development of a prototype sensing garment with sensors in several
      areas on the torso to measure breathing, shoulder movement, neck movement, and
      scapula pressure. Sensor properties were characterized, and data from pilot tests
      was examined visually. RESULTS: The foam exhibits a positive linear conductance
      response to increased pressure. Torso tests show that it responds in a
      predictable and measurable manner to breathing, shoulder movement, neck movement,
      and scapula pressure. CONCLUSION: The polypyrrole foam shows considerable promise
      as a sensor for medical, wearable, and ubiquitous computing applications. Further
      investigation of the foam's consistency of response, durability over time, and
      specificity of response is necessary.

PMID- 15740625
TI  - Locally advanced duodenal gangliocytic paraganglioma treated with adjuvant
      radiation therapy: case report and review of the literature.
AB  - BACKGROUND: Gangliocytic paraganglioma are rare neoplasms that predominantly
      arise in periampulary region. Though considered benign the disease can spread to
      regional lymphatics. CASE PRESENTATION: A 49 year old woman presented with melena
      and was found to have a periampullary mass. Endoscopic evaluation and biopsy
      demonstrated a periampullary paraganglioma. The tumor was resected with pylorus
      preserving pancreaticoduodenectomy and was found to represent a gangliocytic
      paraganglioma associated with nodal metastases. In a controversial decision, the
      patient was treated with adjuvant external beam radiation therapy. She is alive
      and well one year following resection. The authors have reviewed the current
      literature pertaining to this entity and have discussed the biologic behavior of
      the tumor as well as the rationale for treatment strategies employed. CONCLUSION:
      Paraganglioma is a rare tumor that typically resides in the gastrointestinal
      tract and demonstrates low malignant potential. Due to rarity of the disease
      there is no consensus on the adjuvant treatment even though nearly 5% of the
      lesions demonstrate the malignant potential.

PMID- 15740624
TI  - Soilborne wheat mosaic virus (SBWMV) 19K protein belongs to a class of cysteine
      rich proteins that suppress RNA silencing.
AB  - Amino acid sequence analyses indicate that the Soilborne wheat mosaic virus
      (SBWMV) 19K protein is a cysteine-rich protein (CRP) and shares sequence homology
      with CRPs derived from furo-, hordei-, peclu- and tobraviruses. Since the hordei-
      and pecluvirus CRPs were shown to be pathogenesis factors and/or suppressors of
      RNA silencing, experiments were conducted to determine if the SBWMV 19K CRP has
      similar activities. The SBWMV 19K CRP was introduced into the Potato virus X
      (PVX) viral vector and inoculated to tobacco plants. The SBWMV 19K CRP aggravated
      PVX-induced symptoms and restored green fluorescent protein (GFP) expression to
      GFP silenced tissues. These observations indicate that the SBWMV 19K CRP is a
      pathogenicity determinant and a suppressor of RNA silencing.

PMID- 15740626
TI  - A cluster of genes located in 1p36 are down-regulated in neuroblastomas with poor
      prognosis, but not due to CpG island methylation.
AB  - BACKGROUND: A common feature of neuroblastoma tumours are partial deletions of
      the short arm of chromosome 1 (1p-deletions). This is indicative of a
      neuroblastoma tumour suppressor gene being located in the region. Several groups
      including our have been studying candidate neuroblastoma genes in the region, but
      no gene/genes have yet been found that fulfil the criteria for being a
      neuroblastoma tumour suppressor. Since frequent mutations have not been detected,
      we have now analyzed the expression and promoter CpG island methylation status of
      the genes UBE4B, KIF1B, PGD, APITD1, DFFA and PEX14 in the 1p36.22 region in
      order to find an explanation for a possible down-regulation of this region.
      RESULTS: The current study shows that gene transcripts in high stage
      neuroblastoma tumours are significantly down-regulated compared to those in low
      stage tumours in the 1p36.22 region. CpG island methylation does not seem to be
      the mechanism of down-regulation for most of the genes tested, since no
      methylation was detected in the fragments analyzed. One exception is the CpG
      island of APITD1. Methylation of this gene is also seen in blood from control
      individuals and is therefore not believed to participate in tumour development.
      CONCLUSION: The genes UBE4B, KIF1B, PGD, APITD1, DFFA and PEX14 are down
      regulated in high stage NB tumours, a feature that can not be explained by CpG
      island methylation.

PMID- 15740627
TI  - A robust method for the amplification of RNA in the sense orientation.
AB  - BACKGROUND: Small quantities of RNA (1-4 microg total RNA) available from
      biological samples frequently require a single round of amplification prior to
      analysis, but current amplification strategies have limitations that may restrict
      their usefulness in downstream genomic applications. The Eberwine amplification
      method has been extensively validated but is limited by its ability to produce
      only antisense RNA. Alternatives lack extensive validation and are often
      confounded by problems with bias or yield attributable to their greater
      biological and technical complexity. RESULTS: To overcome these limitations, we
      have developed a straightforward and robust protocol for amplification of RNA in
      the sense orientation. This protocol is based upon Eberwine's method but
      incorporates elements of more recent amplification techniques while avoiding
      their complexities. Our technique yields greater than 100-fold amplification,
      generates long transcript, and produces mRNA that is well suited for use with
      microarray applications. Microarrays performed with RNA amplified using this
      protocol demonstrate minimal amplification bias and high reproducibility.
      CONCLUSION: The protocol we describe here is readily adaptable for the production
      of sense or antisense, labeled or unlabeled RNA from intact or partially-degraded
      prokaryotic or eukaryotic total RNA. The method outperforms several commercial
      RNA amplification kits and can be used in conjunction with a variety of
      microarray platforms, such as cDNA arrays, oligonucleotide arrays, and Affymetrix
      GeneChip arrays.

PMID- 15740628
TI  - Low frequency of defective mismatch repair in a population-based series of upper
      urothelial carcinoma.
AB  - BACKGROUND: Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of
      the renal pelvis and the ureter, occur at an increased frequency in patients with
      hereditary nonpolyposis colorectal cancer (HNPCC). Defective mismatch repair
      (MMR) specifically characterizes HNPCC-associated tumors, but also occurs in
      subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial
      cancer. METHODS: We assessed the contribution of defective MMR to the development
      of UUC in a population-based series from the southern Swedish Cancer Registry,
      through microsatellite instability (MSI) analysis and immunohistochemical
      evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. RESULTS:
      A MSI-high phenotype was identified in 9/216 (4%) successfully analyzed patients
      and a MSI-low phenotype in 5/216 (2%). Loss of MMR protein immunostaining was
      found in 11/216 (5%) tumors, and affected most commonly MSH2 and MSH6.
      CONCLUSION: This population-based series indicates that somatic MMR inactivation
      is a minor pathway in the development of UUC, but tumors that display defective
      MMR are, based on the immunohistochemical expression pattern, likely to be
      associated with HNPCC.

PMID- 15740629
TI  - Acute effects of cigarette smoking on inflammation in healthy intermittent
      smokers.
AB  - BACKGROUND: Chronic smoking is the main risk factor for chronic obstructive
      pulmonary disease. Knowledge on the response to the initial smoke exposures might
      enhance the understanding of changes due to chronic smoking, since repetitive
      acute smoke effects may cumulate and lead to irreversible lung damage. METHODS:
      We investigated acute effects of smoking on inflammation in 16 healthy
      intermittent smokers in an open randomised cross-over study. We compared effects
      of smoking of two cigarettes on inflammatory markers in exhaled air, induced
      sputum, blood and urine at 0, 1, 3, 6, 12, 24, 48, 96 and 192 hours and outcomes
      without smoking. All sputum and blood parameters were log transformed and
      analysed using a linear mixed effect model. RESULTS: Significant findings were:
      Smoking increased exhaled carbon monoxide between 0 and 1 hour, and induced a
      greater decrease in blood eosinophils and sputum lymphocytes between 0 and 3
      hours compared to non-smoking. Compared to non-smoking, smoking induced a greater
      interleukin-8 release from stimulated blood cells between 0 and 3 hours, and a
      greater increase in sputum lymphocytes and neutrophils between 3 and 12 hours.
      CONCLUSION: We conclude that besides an increase in inflammation, as known from
      chronic smoking, there is also a suppressive effect of smoking two cigarettes on
      particular inflammatory parameters.

PMID- 15740630
TI  - General practitioner attitudes to the care of people with epilepsy: an
      examination of clustering within practices and prediction of patient-rated
      quality of care.
AB  - BACKGROUND: There is wide variation in the quality of care provided by primary
      care practices to individuals with chronic illnesses. Individual doctor attitudes
      and interest have been demonstrated to influence patient outcomes in some
      instances. Given the trend towards larger practices and part-time working,
      continuity of care is likely to fall and thus practice-based rather than
      individual general practitioner attributes and attitudes are likely to become
      increasingly important. The aim in this paper was to examine the extent to which
      individual general practitioner (G.P.) attitudes to the care of people with
      epilepsy cluster within practices and predict patient-rated quality of care.
      METHODS: The sample consisted of 1255 people with active epilepsy (a recent
      seizure or on anti-convulsant medication for epilepsy) and 199 GPs from 82
      general practices. Measures of GP attitudes (a 17-item GP attitudes
      questionnaire) and patient-rated quality of epilepsy care were obtained. 1210
      individuals completed initial questionnaires and 975 patients filled in final
      questionnaires one year later. Responses were achieved from 64 practices (83% of
      total) and 115 GPs (60% of total). RESULTS: 2 main factors were found to underlie
      GP attitudes to the care of people with epilepsy and these demonstrated
      clustering within practices "epilepsy viewed as a primary care responsibility"
      (Eigenvalue 3.98, intra-class correlation coefficient (ICC) 0.40), and
      "medication skills"(Eigenvalue 2.74, ICC 0.35). GP-rated scores on "epilepsy care
      being a primary care responsibility" were a significant predictor of patient
      rated quality of GP care (p = 0.031). Other contributory factors were seizure
      frequency (p = 0.044), and patient-rated "shared decision making" (p = 0.022).
      CONCLUSION: Specific general practitioner attitudes to the care of people with
      epilepsy cluster within practices and are significantly associated with patient
      rated quality of epilepsy care. It is important to take these findings into
      consideration when planning primary care interventions to ensure people with
      epilepsy receive the benefits of available medical and surgical expertise.

PMID- 15740631
TI  - Age and manifestation related symptoms in familial adenomatous polyposis.
AB  - BACKGROUND: To identify early symptoms of familial adenomatous polyposis with a
      view to improve early diagnosis and treatment. Diagnosis on the basis of genetic
      testing is usually limited to where there is a known family history, so FAP is
      more usually diagnosed on clinical grounds. Except for those identified via FAP
      registers, the majority of patients are symptomatic at the time of diagnosis.
      METHODS: We undertook a retrospective study of 143 FAP patients treated at the
      Department of Surgery, University of Erlangen between 1971 and 2000. We
      identified patterns of symptoms, endoscopic findings and extracolonic
      manifestations in three age groups. RESULTS: FAP was diagnosed clinically on the
      basis of symptoms in 84% (120/143) of these patients. Most presented with
      intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but
      one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76),
      whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific
      symptoms such as abdominal pain, fatigue and bloating were less frequent and were
      mainly reported by patients older than 40. CONCLUSION: The commonest presenting
      features of FAP are alteration of bowel habit and rectal bleeding, but both are
      found in many other conditions. Patients with these findings need immediate
      endoscopy to allow prompt diagnosis and prophylactic surgery.

PMID- 15740632
TI  - Wearable Conductive Fiber Sensors for Multi-Axis Human Joint Angle Measurements.
AB  - BACKGROUND: The practice of continuous, long-term monitoring of human joint
      motion is one that finds many applications, especially in the medical and
      rehabilitation fields. There is a lack of acceptable devices available to perform
      such measurements in the field in a reliable and non-intrusive way over a long
      period of time. The purpose of this study was therefore to develop such a
      wearable joint monitoring sensor capable of continuous, day-to-day monitoring.
      METHODS: A novel technique of incorporating conductive fibers into flexible, skin
      tight fabrics surrounding a joint is developed. Resistance changes across these
      conductive fibers are measured, and directly related to specific single or multi
      axis joint angles through the use of a non-linear predictor after an initial, one
      time calibration. Because these sensors are intended for multiple uses, an
      automated registration algorithm has been devised using a sensitivity template
      matched to an array of sensors spanning the joints of interest. In this way, a
      sensor array can be taken off and put back on an individual for multiple uses,
      with the sensors automatically calibrating themselves each time. RESULTS: The
      wearable sensors designed are comfortable, and acceptable for long-term wear in
      everyday settings. Results have shown the feasibility of this type of sensor,
      with accurate measurements of joint motion for both a single-axis knee joint and
      a double axis hip joint when compared to a standard goniometer used to measure
      joint angles. Self-registration of the sensors was found to be possible with only
      a few simple motions by the patient. CONCLUSION: After preliminary experiments
      involving a pants sensing garment for lower body monitoring, it has been seen
      that this methodology is effective for monitoring joint motion of the hip and
      knee. This design therefore produces a robust, comfortable, truly wearable joint
      monitoring device.

PMID- 15740633
TI  - Vaccination of metastatic melanoma patients with autologous dendritic cell (DC)
      derived-exosomes: results of thefirst phase I clinical trial.
AB  - BACKGROUND: DC derived-exosomes are nanomeric vesicles harboring functional
      MHC/peptide complexes capable of promoting T cell immune responses and tumor
      rejection. Here we report the feasability and safety of the first Phase I
      clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the
      immunization of stage III/IV melanoma patients. Secondary endpoints were the
      monitoring of T cell responses and the clinical outcome. PATIENTS AND METHODS:
      Exosomes were purified from day 7 autologous monocyte derived-DC cultures.
      Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+,
      or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were
      enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose
      levels of either MHC class II molecules (0.13 versus 0.40 x 1014 molecules) or
      peptides (10 versus 100 mug/ml) were tested. Evaluations were performed before
      and 2 weeks after immunization. A continuation treatment was performed in 4 cases
      of non progression. RESULTS: The GMP process allowed to harvest about 5 x 1014
      exosomal MHC class II molecules allowing inclusion of all 15 patients. There was
      no grade II toxicity and the maximal tolerated dose was not achieved. One patient
      exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+
      patient vaccinated with A1/B35 defined CTL epitopes developed halo of
      depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response
      in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules
      on tumor cells during therapy with exosomes. In addition, one minor, two stable
      and one mixed responses were observed in skin and lymph node sites. MAGE3
      specific CD4+ and CD8+ T cell responses could not be detected in peripheral
      blood. CONCLUSION: The first exosome Phase I trial highlighted the feasibility of
      large scale exosome production and the safety of exosome administration.

PMID- 15740634
TI  - Computational verification of protein-protein interactions by orthologous co
      expression.
AB  - BACKGROUND: High-throughput methods identify an overwhelming number of protein
      protein interactions. However, the limited accuracy of these methods results in
      the false identification of many spurious interactions. Accordingly, the
      resulting interactions are regarded as hypothetical and computational methods are
      needed to increase their confidence. Several methods have recently been suggested
      for this purpose including co-expression as a confidence measure for interacting
      proteins, but their performance is still quite poor. RESULTS: We introduce a
      novel computational method for verification of protein-protein interactions based
      on the co-expression of orthologs of interacting partners. The performance of our
      method is analysed using known S. cerevisiae interactions, and is shown to
      overcome limitations of previous methods. We present specific examples of known
      and putative interactions that are detected by our method and not by previous
      methods, and suggest that they represent transient interactions that might have
      been conserved and stabilized in other species. CONCLUSION: Co-expression of
      orthologous protein-pairs can be used to increase the confidence of hypothetical
      protein-protein interactions in S. cerevisiae as well as in other species. This
      approach may be especially useful for species with no available expression
      profiles and for transient interactions.

PMID- 15740635
TI  - Inositol 1,4,5-trisphosphate 3-kinases: functions and regulations.
AB  - Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP(3)K) plays an important
      role in signal transduction in animal cells by phosphorylating inositol 1,4,5
      trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP(4)). Both IP(3) and
      IP(4) are critical second messengers which regulate calcium (Ca(2+)) homeostasis.
      Mammalian IP3Ks are involved in many biological processes, including brain
      development, memory, learning and so on. It is widely reported that Ca(2+) is a
      canonical second messenger in higher plants. Therefore, plant IP3K should also
      play a crucial role in plant development. Recently, we reported the
      identification of plant IP3K gene (AtIpk2beta/AtIP3K) from Arabidopsis thaliana
      and its characterization. Here, we summarize the molecular cloning, biochemical
      properties and biological functions of IP3Ks from animal, yeast and plant. This
      review also discusses potential functions of IP3Ks in signaling crosstalk,
      inositol phosphate metabolism, gene transcriptional control and so on.

PMID- 15740637
TI  - SHEsis, a powerful software platform for analyses of linkage disequilibrium,
      haplotype construction, and genetic association at polymorphism loci.
AB  - In multiloci-based genetic association studies of complex diseases, a powerful
      and high efficient tool for analyses of linkage disequilibrium (LD) between
      markers, haplotype distributions and many chi-square/p values with a large number
      of samples has been sought for long. In order to achieve the goal of obtaining
      meaningful results directly from raw data, we developed a robust and user
      friendly software platform with a series of tools for analysis in association
      study with high efficiency. The platform has been well evaluated by several sets
      of real data.

PMID- 15740636
TI  - Kruppel-like factors 4 and 5: the yin and yang regulators of cellular
      proliferation.
AB  - Kruppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing
      transcription factors with diverse regulatory functions in cell growth,
      proliferation, differentiation, and embryogenesis. KLF4 and KLF5 are two closely
      related members of the KLF family that have a similar tissue distribution in
      embryos and adults. However, the two KLFs often exhibit opposite effects on
      regulation of gene transcription, despite binding to similar, if not identical,
      cis-acting DNA sequences. In addition, KLF4 and 5 exert contrasting effects on
      cell proliferation in many instances; while KLF4 is an inhibitor of cell growth,
      KLF5 stimulates proliferation. Here we review the biological properties and
      biochemical mechanisms of action of the two KLFs in the context of growth
      regulation.

PMID- 15740638
TI  - Ontogeny of rat chondrocyte proliferation: studies in embryo, adult and
      osteoarthritic (OA) cartilage.
AB  - The aim of this work was to study the ontogeny of chondrocyte cell division using
      embryo, adult and osteoarthritic (OA) cartilage. We searched for mitosis phases
      and performed a comparative evaluation of mitotic index, basic fibroblast growth
      factor b (FGFb), transforming growth factor beta1 (TGF-beta1) receptors, cyclin
      dependent kinase (CDK1) and Cyclin-B expression in fetal, neonate, 3, 5, 8 weeks
      old rats and experimental OA. Our results showed that mitosis phases were
      observed in all normal cartilage studied, although, we found a decrease in
      mitotic index in relation to tissue development. No mitosis was detected in OA
      cartilage. We also found a statistical significant reduction in cell number in OA
      cartilage, compared with the normal tissue. Furthermore, FGFb and TGF-beta1
      receptors diminished in relation to tissue development, and were very scarce in
      experimental OA. Western blot assays showed CDK-1 expression in all cases,
      including human-OA cartilage. Similar results were observed for Cyclin-B, except
      for 8 weeks, when it was not expressed. Our results suggest that cell division
      seems to be scarce, if not absent within the OA cartilage studied. Nevertheless,
      the existence of factors essential for cell division leaves open the question
      concerning chondrocyte proliferation in OA cartilage, which is likely to be
      present in the early stages of the disease.

PMID- 15740639
TI  - Transglutaminase 3 expression in C57BL/6J mouse embryo epidermis and the
      correlation with its differentiation.
AB  - Epidermal-type transglutaminase 3 (TGM3) is involved in the cross-linking of
      structural proteins to form the cornified envelope in the epidermis. In the
      present study, we detected the expression of TGM3 in the mouse embryo using RT
      PCR. TGM3 mRNA is weakly presented from E11.5 to E14.5 and increases
      significantly from E15.5 to birth. Then we determined the spatial and temporal
      expression pattern of TGM3 in the skin and other organs by in situ hybridization.
      We found a deprivation of TGM3 in skin at E11.5, while a rich supply in periderm
      cells and a weak expression in basal cells from E12.5 to E14.5. From the period
      of E15.5 to E16.5, after keratinization in the epidermis, TGM3 was expressed in
      the granular and cornified layers. The electron microscopic observation of the
      C57BL/6J mouse limb bud skin development provided several morphological evidences
      for the epidermal differentiation. The above findings suggest that the expression
      of TGM3 plays a important role in the epidermis differentiation in embryogenesis.

PMID- 15740640
TI  - Down-regulation of IL-8 expression in human airway epithelial cells through
      helper-dependent adenoviral-mediated RNA interference.
AB  - Interleukin (IL)-8 is a potent neutrophil chemotactic factor and a crucial
      mediator in neutrophil-dependent inflammation. Various cell types produce IL-8,
      either in response to external stimuli such as cytokines or bacterial infection,
      or after malignant transformation. Anti-IL-8 strategies have been considered for
      anti-inflammatory therapy. In this paper we demonstrate that the RNA interference
      technique can be used to efficiently down-regulate IL-8 protein expression in
      airway epithelial cells. We used a helper-dependent adenoviral vector to express
      a small hairpin (sh)RNA targeting human IL-8 in cultured airway epithelial cells
      (IB3-1, Cftr-/-; C38, Cftr-corrected) stimulated with TNF-alpha, IL-1beta or heat
      inactivated Burkholderia cenocepacia. Stimulated IL-8 expression in IB3-1 and C38
      cells was significantly reduced by shRNA expression. The shRNA targeting IL-8 had
      no effect on the activation of NF-kappaB, or on the protein levels of IkappaB or
      IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore
      may offer potential for the treatment of inflammatory diseases.

PMID- 15740641
TI  - Dynamic distribution of Ser-10 phosphorylated histone H3 in cytoplasm of MCF-7
      and CHO cells during mitosis.
AB  - The dynamic distribution of phosphorylated Histone H3 on Ser10 (phospho-H3) in
      cells was investigated to determine its function during mitosis. Human breast
      adenocarcinoma cells MCF-7, and Chinese hamster cells CHO were analyzed by
      indirect immunofluorescence staining with an antibody against phospho-H3. We
      found that the phosphorylation begins at early prophase, and spreads throughout
      the chromosomes at late prophase. At metaphase, most of the phospho-H3 aggregates
      at the end of the condensed entity of chromosomes at equatorial plate. During
      anaphase and telophase, the fluorescent signal of phospho-H3 is detached from
      chromosomes into cytoplasm. At early anaphase, phospho-H3 shows ladder bands
      between two sets of separated chromosome, and forms "sandwich-like structure"
      when the chromosomes condensed. With the cleavage progressing, the "ladders" of
      the histone contract into a bigger bright dot. Then the histone aggregates and
      some of compacted microtubules in the midbody region are composed into a "bar
      like" complex to separate daughter cells. The daughter cells seal their plasma
      membrane along with the ends of the "bar", inside which locates microtubules and
      modified histones, to finish the cytokinesis and keep the "bar complex" out of
      the cells. The specific distribution and kinetics of phospho-H3 in cytoplasm
      suggest that the modified histones may take part in the formation of midbody and
      play a crucial role in cytokinesis.

PMID- 15740642
TI  - Role of the first mitosis in the remodeling of the parental genomes in mouse
      embryos.
AB  - Although male and female pronuclei reside in the same zygotic cytoplasm, they
      differ in many respects, such as volume and transcriptional activity. The aim of
      this study is to investigate whether these differences are lost during the first
      mitosis. For this purpose, a new method was developed to inhibit the mixing of
      two parental chromosomes during mitosis, thus to induce the formation of two
      nuclei after they exit from the mitotic phase. In this method, one-cell embryos
      are arrested at metaphase by treatment with nocodazole, and whn exitting from the
      mitotic phase, two nuclei were formed in a single karyocyte following treatment
      with 6-dimethylaminopurine (6-DMAP). These embryos were designated as post
      mitotic embryos (PM-embryos), in which the two nuclei were derived from the male
      and female genomes. We found that in the control one-cell embryos that had not
      been treated with the reagents, the volume of the male pronucleus was about 1.65
      fold greater than that of the female pronucleus, whereas the volumes of the two
      nuclei in the PM-embryos were similar (volume ratio of 1.01). Although a two-fold
      difference in transcriptional activity was detected between the male and female
      pronuclei in the control embryos, no difference in transcriptional activity was
      detected between the two nuclei of PM-embryos. The ratio of transcriptional
      activity in the nucleus derived from the paternal genome to that from the
      maternal genome was 1.02, for which no significant difference was detected by the
      c2 fitness test. Therefore, the volumes and transcriptional activities of the
      male and female nuclei were approximately equal in PM-embryos, which suggests
      that the asymmetries of pronuclear volume and transcriptional activity between
      male and female genomes are somehow losted during the first mitosis.

PMID- 15740643
TI  - Characterization of a novel developmentally retarded mutant (drm1) associated
      with the autonomous flowering pathway in Arabidopsis.
AB  - A developmentally retarded mutant (drm1) was identified from ethyl
      methanesulfonate (EMS)-mutagenized M2 seeds in Columbia (Col-0) genetic
      background. The drm1 flowers 109 d after sowing, with a whole life cycle of about
      160 d. It also shows a pleiotropic phenotype, e.g., slow germination and lower
      germination rate, lower growth rate, curling leaves and abnormal floral organs.
      The drm1 mutation was a single recessive nuclear mutation, which was mapped to
      the bottom of chromosome 5 and located within a region of 20-30 kb around MXK3.1.
      There have been no mutants with similar phenotypes reported in the literature,
      suggesting that DRM1 is a novel flowering promoting locus. The findings that the
      drm1 flowered lately under all photoperiod conditions and its late flowering
      phenotype was significantly restored by vernalization treatment suggest that the
      drm1 is a typical late flowering mutant and most likely associated with the
      autonomous flowering pathway. The conclusion was further confirmed by the
      revelation that the transcript level of FLC was constantly upregulated in the
      drm1 at all the developmental phases examined, except for a very early stage.
      Moreover, the transcript levels of two other important repressors, EMF and TFL1,
      were also upregulated in the drm1, implying that the two repressors, along with
      FLC, seems to act in parallel pathways in the drm1 to regulate flowering as well
      as other aspects of floral development in a negatively additive way. This helps
      to explain why the drm1 exhibits a much more severe late-flowering phenotype than
      most late-flowering mutants reported. It also implies that the DRM1 might act
      upstream of these repressors.

PMID- 15740644
TI  - Potent antitumoral effects of a novel gene-viral therapeutic system CNHK300
      mEndostatin in hepatocellular carcinoma.
AB  - BACKGROUND: The expression of therapeutic gene and its anti-tumor effects will be
      augmented and a synergism of oncolytic virus with the therapeutic gene is
      speculated. This study was undertaken to assess the anti-tumor effects of a novel
      gene-viral therapeutic system CNHK300-mEndostatin (CNHK300-mE) in hepatocellular
      carcinoma (HCC). METHODS: A novel gene-viral therapeutic system named CNHK300-mE
      was constructed using the human telomerase reverse transcriptase (hTERT) promoter
      to drive the expression of the adenovirus E1A gene and cloning the therapeutic
      gene mouse endostatin into the adenovirus genome. By the tissue culture
      infectious dose 50 (TCID50) method and cytoviability assay, the replicative and
      cytolytic capabilities of CNHK300-mE in two HCC lines (HepGII and Hep3B) and one
      normal cell line (MRC-5) were analyzed, and the transgene expressions of mouse
      endostatin in vitro and in vivo were detected by Western blotting and ELISA
      assay. Tumor growth suppression and anti-angiogenesis effects in vivo were
      investigated using nude mice xenografts model derived from SMMC-7721 HCC cells.
      RESULTS: The 3296-fold replicating capacity of CNHK300-mE in HCC cell lines
      versus in the normal cell line at 96 hours post infection and the 25-fold
      effective dose for killing 50% cells (ED50) in the normal cell line versus HCC
      cell lines, which were both superior to ONYX-015, were observed. Tumor growth
      suppression of CNHK300-mE superior to either Ad-mE or ONYX-015 was demonstrated
      (P < 0.01) and the anti-angiogenic effects in vivo superior to Ad-mE were also
      observed with immunohistochemical staining of von Willebrand factor. In
      comparison with non-replicative adenovirus Ad-mE, the transgene expression of mE
      mediated by CNHK300-mE was significantly higher in vitro (P < 0.005) and in vivo
      (P < 0.05). CONCLUSION: Being capable of replicating in and lysing the telomerase
      positive HCC cells and mediating effective expression of the therapeutic gene in
      vitro and in vivo, the novel gene-viral therapeutic system CNHK300-mE is
      potentially effective in the treatment of HCC.

PMID- 15740645
TI  - Morphological and distribution characteristics of sweat glands in hypertrophic
      scar and their possible effects on sweat gland regeneration.
AB  - BACKGROUND: In hypertrophic scar tissue, no sweet gland and hair follicle exist
      usually because of the dermal and epidermal damage in extensive thermal skin
      injury, thus imparing regulation of body temperature. This study was designed to
      reveal the morphological and distributional characteristics of the sweat glands
      in normal skin and hypertrophic scar obtained from children and adults, and to
      study the possible interfering effects of the scar on regeneration of the sweat
      gland after burn injury. METHODS: Biopsies of hypertrophic scar were taken from
      four children (4 - 10 years) and four adults (35 - 51 years). Normal, uninjured
      full-thickness skin adjacent to the scar of each patient was used as control.
      Keratin 19 (K19) was used as the marker for epidermal stem cells and secretory
      portion of the sweat glands, and keratin 14 (K14) for the tube portion,
      respectively. Immunohistochemical and histological evaluations were performed.
      RESULTS: Histological and immunohistochemical staining of skin tissue sections
      from both the children and adults showed K19 positive cells in the basement
      membrane of epidermis of normal skin. These cells were seen only single layer and
      arranged regularly. The secretory or duct portion of the eccrine sweat glands was
      situated in the dermis and epidermal layer. However, in the scar tissue, K19
      positive cells were scant in the basal layer, and the anatomic location of the
      secretory portion of sweat glands changed. They were located between the border
      of the scar and reticular layer of the dermis. These secretory portions of sweat
      glands were expanded and were organized irregularly. But a few K14 positive cells
      were scattered in the scar tissues in cyclic form. CONCLUSIONS: There are some
      residual sweat glands in scar tissues, in which the regeneration process of
      active sweat glands is present. Possibly the sweat glands could regenerate from
      adult epidermal stem cells or residual sweat glands in the wound bed after burn
      injury.

PMID- 15740646
TI  - Effects of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1
      on liver fibrosis in rats.
AB  - BACKGROUND: No efficient therapy for liver fibrosis has been available. This
      study was aimed to provide evidence that the introduction of a plasmid expressing
      antisense tissue inhibitor of metalloproteinase-1 (TIMP-1) into a rat model of
      immunologically induced liver fibrosis can result in the increased activity of
      interstitial collagenase, thus enhancing the degradation of collagen. METHODS:
      Real-time nested polymerase chain reaction (RT-Nested-PCR) and gene recombination
      techniques were used to construct a rat antisense TIMP-1 recombinant plasmid that
      can be expressed in eukaryotic cells. Both the recombinant plasmid and an empty
      vector (pcDNA3) were encapsulated with glycosyl-poly-L-lysine and injected into
      rats suffering from pig serum-induced liver fibrosis. The expression of exogenous
      transfected plasmid was assessed by Northern blot, RT-PCR, and Western blot.
      Hepatic interstitial collagenase activity was detected using
      fluorescinisothiocyanate (FITC)-labeled type I collagen. In addition to hepatic
      hydroxyproline content, hepatic collagen types I and III were detected by
      immunohistochemical staining, and the stages of liver fibrosis by Van Gieson
      staining. RESULTS: Exogenous antisense TIMP-1 was successfully expressed in vivo
      and could block the gene and protein expression of TIMP-1. Active and latent
      hepatic interstitial collagenase activities were elevated (P < 0.01), hepatic
      hydroxyproline content and the accumulation of collagen types I and III were
      lowered, and liver fibrosis was alleviated in the antisense TIMP-1 group (P <
      0.01) as compared with the model group. CONCLUSION: The results demonstrate that
      antisense TIMP-1 recombinant plasmids have some inhibitory effect on liver
      fibrosis.

PMID- 15740647
TI  - Mitogen-activated protein kinase-dependent apoptosis in norcan-tharidin-treated
      A375-S2 cells is proceeded by the activation of protein kinase C.
AB  - BACKGROUND: We have reported that norcantharidin (NCTD) induces human melanoma
      A375-S2 cell apoptosis and that the activation of caspase and the mitochondrial
      pathway are involved in the apoptotic process. This study aimed at investigating
      the roles of mitogen-activated protein kinase (MAPK) and protein kinase C (PKC)
      in A375-S2 cell apoptosis induced by NCTD. METHODS: We assessed the effects of
      NCTD on cell growth inhibition using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      dipheyltetrazolium bromide (MTT) assay, DNA fragmentation (DNA agarose gel
      electrophoresis), and MAPK protein levels (Western blot analysis) in A375-S2
      cells. Photomicroscopic data were also collected. RESULTS: The NCTD inhibitory
      effect on A375-S2 cells was partially reversed by MAPK and PKC inhibitors. The
      expression of phosphorylated JNK and p38 also increased after the treatment with
      NCTD, and inhibitors of c-Jun NH2-terminal kinase (JNK) and p38 (SP600125 and
      SB203580, respectively) had significant inhibitory effects on the upregulation of
      phosphorylated JNK and p38 expression. Simultaneously, the PKC inhibitor
      staurosporine blocked the upregulation of phosphorylated JNK and phosphorylated
      p38, but had little effect on extracellular signal-regulated kinase (ERK)
      expression. CONCLUSION: These results suggest that the activation of JNK and p38
      MAPK promotes the process of NCTD-induced A375-S2 cell apoptosis and that PKC
      plays an important regulation role in the activation of MAPKs.

PMID- 15740648
TI  - Optimising gene therapy of hypoparathyroidism with hematopoietic stem cells.
AB  - BACKGROUND: The treatment of hypoparathyroidism (HPT) is still a difficult
      clinical problem, which necessitates a new therapy. Gene therapy of HPT has been
      valuable, but how to improve the gene transfer efficiency and expression
      stability is a problem. This study was designed to optimize the gene therapy of
      HPT with hematopoietic stem cells (HSCs) recombined with the parathyroid hormone
      (PTH) gene. METHODS: The human PTH gene was amplified by polymerase chain
      reaction (PCR) from pcDNA3.1-PTH vectors and inserted into murine stem cell virus
      (MSCV) vectors with double enzyme digestion (EcoRI and XhoI). The recombinant
      vectors were transfected into PA317 packaging cell lines by the lipofectin method
      and screened by G418 selective medium. The condensed recombinant retroviruses
      were extracted and used to infect HSCs, which were injected into mice suffering
      from HPT. The change of symptoms and serum levels of PTH and calcium in each
      group of mice were investigated. RESULTS: The human PTH gene was inserted into
      MSCV vectors successfully and the titres were up to 2 x 10(7) colony forming unit
      (CFU)/ml in condensed retroviral solution. The secretion of PTH reached 15 ng.10(
      6).cell(-1) per 48 hours. The wild type viruses were not detected via PCR
      amplification, so they were safe for use. The mice suffering from HPT recovered
      quickly and the serum levels of calcium and PTH remained normal for about three
      months after the HSCs recombined with PTH were injected into them. The
      therapeutic effect of this method was better than simple recombinant retroviruses
      injection. CONCLUSIONS: The recombinant retroviral vectors MSCV-PTH and the high
      titre condensed retroviral solution recombined with the PTH gene are obtained.
      The recombinant retroviral solution could infect HSCs at a high rate of
      efficiency. The infected HSCs could cure HPT in mice. This method has provided
      theoretical evidence for the clinical gene therapy of HPT.

PMID- 15740649
TI  - Manometric asymmetry of the anal sphincter: anatomic evidence and clinical
      application.
AB  - BACKGROUND: Manometric pressure asymmetry of the anal sphincter exists in the
      anal canal. There are reports about the anatomy of the anal sphincter, but the
      relationship between the configuration and the pressure asymmetry of the anal
      sphincter is not clear. This study is to investigate the anatomic evidence and
      clinical application of anal sphincter pressure asymmetry. METHODS: PC polygram
      HR at the state of relaxing and squeezing was used in 27 normal children and 12
      abnormal ones with fecal incontinence. RESULTS: In normal children, longitudinal
      pressure gradients existed at eight channels in the anal canal, and the maximal
      pressure 1 cm from the anal verge. Longitudinal pressure asymmetry changes of
      eight channels also existed in the anal canal, from 3 cm to 2 cm to 1 cm from the
      anal verge. The high pressure distribution changed from the posterior to the
      anterior anal canal. Anteriorly, 1 cm from the anal verge, the maximal pressure
      was formed in the anal canal. However, neither longitudinal pressure gradients
      nor longitudinal pressure asymmetry changes were seen in patients with fecal
      incontinence. CONCLUSION: The configuration and function of the striated muscle
      complex possibly contribute to the formation of the pressure asymmetry of the
      anal sphincter, which is essential to anal control.

PMID- 15740650
TI  - Cutaneous lesions and visceral involvement of tuberous sclerosis.
AB  - BACKGROUND: Tuberous sclerosis (TS) is an autosomal dominant disorder with a
      significant range of clinical expressions. The involvement of vital organs, such
      as the brain, kidney, heart and lung is the main cause of death in patients with
      TS. The aim of this study is to summarize the characteristic cutaneous features
      and common extracutaneous involvement of TS, which are helpful to the early
      detection of visceral involvement. METHODS: The analyzed clinical data from 78
      patients with TS included those from detailed history, physical and
      dermatological examination, cranial computed tomography (CT) and magnetic
      resonance imaging (MRI), abdominal ultrasonography, chest roentgenography, hand
      and foot X-ray and ophthalmologic examination. RESULTS: The skin, brain and
      kidney were involved frequently in TS patients. Hypomelanotic macules were the
      most common and earliest cutaneous lesions. Their number was more than 3 in 81.5%
      of the patients. They were followed by facial angiofibromas and Shangreen's patch
      in a decreasing frequency. Forehead plaque, facial angiofibromas and Shagreen's
      patch appeared in patients at mean age of 2.6, 6.0 and 8.1 years respectively.
      Cranial CT showed a high positive rate in TS patients. CONCLUSIONS: Cutaneous
      features of TS are helpful in the early diagnosis of the disease. Hypomelanotic
      macules are especially important for patients with epilepsy or babies whose
      number of hypomelanotic macules is more than 3. Cranial CT is of great value in
      the diagnosis of TS. The involvement of visceral organs such as the brain and
      kidney should be examined in TS patients.

PMID- 15740651
TI  - Effects of granulocyte-macrophage colony stimulating factor on the repair of
      vessel intima damaged by balloon.
AB  - BACKGROUND: The dysfunction of vascular endothelial cells plays a key role in
      starting and facilitating restenosis. The acceleration of intima repair and the
      recovery of endothelial function would reduce the restenosis rate. This study was
      undertaken to assess the effect of granulocyte-macrophage colony stimulating
      factor (GM-CSF) on the repair of damaged iliac arteries. METHODS: Twenty-four
      male New Zealand white rabbits undergoing primary iliac artery deendothelization
      were randomly divided into two groups (GM-CSF group and control group). The GM
      CSF group received a subcutaneous injection of GM-CSF [10 microg x kg(-1) x d(
      1)], and the control group was given a subcutaneous injection of equivalent
      saline. The iliac arteries of all animals were damaged by balloon after 7 days.
      The levels of nitric oxide (NO) were detected before, 1 week, 2 weeks and 4 weeks
      after angioplasty. The repair and hyperplasia of the intima were observed
      microscopically and the indices of stenosis were evaluated by computerized
      planimetry after 4 weeks of angioplasty. RESULTS: The NO levels of the GM-CSF
      group were higher than those of the control group 2 weeks and 4 weeks after
      angioplasty [(91.92 +/- 11.57) micromol/L vs. (81.67 +/- 12.18) micromol/L;
      (97.67 +/- 10.13) micromol/L vs. (83.16 +/- 12.64) micromol/L]. Four weeks after
      balloon damage, histological examination showed that neointima formation,
      vascular smooth muscle cells and fibrous tissue of the GM-CSF group were less
      than those of the control group. The endothelium of the GM-CSF group was more
      integrated, and stenosis of lumen was slighter than that of the control group.
      Morphometry showed the lumen area of the GM-CSF group was larger than that of the
      control group [(1.27 +/- 0.31) mm(2) vs. (0.92 +/- 0.24) mm(2)], the neointimal
      area and percent of intima hyperplasia were significantly smaller than those of
      the control group [(0.85 +/- 0.34) mm(2) vs. (1.18 +/- 0.38) mm(2); (40 +/- 7)%
      vs. (55 +/- 6)%]. CONCLUSION: GM-CSF could facilitate the repair of the intima,
      reduce neointima formation, better the function of the endothelium, and decrease
      the rate of restenosis.

PMID- 15740652
TI  - Effects of Smac gene over-expression on the radiotherapeutic sensitivities of
      cervical cancer cell line HeLa.
AB  - BACKGROUND: The second mitochondria-derived activator of caspases (Smac) is a
      novel proapoptotic gene, which plays an important role in the apoptosis-inducing
      effects of irradiation on tumor cells. The purpose of this study was to
      investigate the effects of extrinsic Smac gene transfer and its over-expression
      in radiotherapeutic sensitivities of cervical cancer cells. METHODS: After the
      Smac gene was transferred into the cervical cancer cell line HeLa, subcloned
      cells were obtained by persistent G418 selection. Cellular Smac gene expression
      was detected by RT-PCR and Western blot, while in vitro cell viabilities were
      detected by trypan blue staining assay. After treatment with X-ray irradiation,
      cellular radiotherapeutic sensitivities were investigated by tetrazolium bromide
      colorimetry. Cellular apoptosis and its rate were determined by electronic
      microscopy, annexin V-FITC and propidium iodide staining flow cytometry. The
      expression and activities of cellular caspase-3 were assayed by Western blot and
      colorimetry. RESULTS: Smac mRNA and protein levels in HeLa/Smac cells and the
      selected subclone cell line of cervical cancer were significantly higher than
      those of HeLa (P < 0.01). There was no significant difference in cellular
      viabilities between them (P > 0.05). However, after irradiation with 8 Gy X-ray,
      growth activities of HeLa/Smac were reduced by 22.42% (P < 0.01). When compared
      with those of HeLa, partial HeLa/Smac cells presented characteristic
      morphological changes of apoptosis under electronic microscope, with higher
      apoptosis rates (16.4% vs. 6.2%, P < 0.01); the caspase-3 expression levels in
      HeLa/Smac cells were improved significantly (P < 0.01), while its activities were
      increased by 3.42 times (P < 0.01). CONCLUSIONS: Stable transfer of the extrinsic
      Smac gene and its over-expression in cervical cancer cell line could
      significantly enhance the expression and activities of cellular caspase-3 and
      ameliorate apoptosis-inducing effects of irradiation on cancer cells, which was a
      novel strategy to improve radiotherapeutic effects on cervical cancer.

PMID- 15740653
TI  - Effects of irbesartan on atrial cell electrophysiology.

PMID- 15740654
TI  - Clinical investigation on diagnostic value of interferon-gamma, interleukin-12
      and adenosine deaminase isoenzyme for tuberculous pleurisy.

PMID- 15740655
TI  - Polymorphism of the second exon of human leukocyte antigen-DQA1, -DQB1 gene and
      genetic susceptibility to idiopathic dilated cardiomyopathy in people of the Han
      nationality in northern China.

PMID- 15740657
TI  - Experience with transperitoneal laparoscopic dismembered pyeloplasty.

PMID- 15740656
TI  - Synergic anti-tumour effect of B7.1 gene modified tumour vaccine combined with
      allicin for murine bladder tumour.

PMID- 15740658
TI  - A scoring model for predicting the prognosis of severe viral hepatitis.

PMID- 15740659
TI  - Comparison of Coombs' and immunocapture-agglutination tests in the diagnosis of
      brucellosis.

PMID- 15740660
TI  - Primary cutaneous aspergillosis due to Aspergillus flavus: a case report.

PMID- 15740661
TI  - Unusual prostate carcinoma characterized by extensive metastasis, significantly
      increased serum level of prostatic-specific antigen,and neuroendocrine
      differentiation: a case report.

PMID- 15740662
TI  - Heavy infection with Armillifer moniliformis: a case report.

PMID- 15740664
TI  - Cultured human embryonic neocortical cells survive and grow in infarcted cavities
      of adult rat brains and interconnect with host brain.
AB  - BACKGROUND: There are no reports on exnografting cultured human fetal neocortical
      cells in this infracted cavities of adult rat brains. This study was undertaken
      to observe whether cultured human cortical neurons and astrocytes can survive and
      grow in the infarcted cavities of adult rat brains and whether they interconnect
      with host brains. METHODS: The right middle cerebral artery was ligated distal to
      the striatal branches in 16 adult stroke-prone renovascular hypertensive rats.
      One week later, cultured cells from human embryonic cerebral cortexes were
      stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats
      receiving sham transplants served as controls. For immunosuppression, all
      transplanted rats received intraperitoneal injection of cyclosporine A daily
      starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic
      protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein
      2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after
      transplantation. RESULTS: Grafts in the infarcted cavities of 6 of 10 surviving
      rats consisted of bands of neurons with an immature appearance, bundles of
      fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The
      grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with
      long processes. The graft/host border was diffuse with dendrites apparently
      bridging over to the host brain, into which neurofilament immunopositive fibers
      protruded. CONCLUSION: Cultured human fetal brain cells can survive and grow in
      the infarcted cavities of immunodepressed rats and integrate with the host brain.

PMID- 15740663
TI  - The protein X4 of severe acute respiratory syndrome-associated coronavirus is
      expressed on both virus-infected cells and lung tissue of severe acute
      respiratory syndrome patients and inhibits growth of Balb/c 3T3 cell line.
AB  - BACKGROUND: The genome of the severe acute respiratory syndrome-associated
      coronavirus (SARS-CoV) includes sequences encoding the putative protein X4 (ORF8,
      ORF7a), consisting of 122 amino acids. The deduced sequence contains a probable
      cleaved signal peptide sequence and a C-terminal transmembrane helix, indicating
      that protein X4 is likely to be a type I membrane protein. This study was
      conducted to demonstrate whether the protein X4 was expressed and its essential
      function in the process of SARS-CoV infection. METHODS: The prokaryotic and
      eukaryotic protein X4-expressing plasmids were constructed. Recombinant soluble
      protein X4 was purified from E. coli using ion exchange chromatography, and the
      preparation was injected into chicken for rising specific polyclonal antibodies.
      The expression of protein X4 in SARS-CoV-infected Vero E6 cells and lung tissues
      from patients with SARS was performed using immunofluorescence assay and
      immunohistochemistry technique. The preliminary function of protein X4 was
      evaluated by treatment with and over-expression of protein X4 in cell lines.
      Western blot was employed to evaluate the expression of protein X4 in SARS-CoV
      particles. RESULTS: We expressed and purified soluble recombinant protein X4 from
      E.coli, and generated specific antibodies against protein X4. Western blot proved
      that the protein X4 was not assembled in the SARS-CoV particles. Indirect
      immunofluorescence assays revealed that the expression of protein X4 was detected
      at 8 hours after infection in SARS-CoV-infected Vero E6 cells. It was also
      detected in the lung tissues from patients with SARS. Treatment with and
      overexpression of protein X4 inhibited the growth of Balb/c 3T3 cells as
      determined by cell counting and MTT assays. CONCLUSION: The results provide the
      evidence of protein X4 expression following SARS-CoV infection, and may
      facilitate further investigation of the immunopathological mechanism of SARS.

PMID- 15740665
TI  - The ectopic study of tissue-engineered bone with hBMP-4 gene modified bone marrow
      stromal cells in rabbits.
AB  - BACKGROUND: Tissue-engineering techniques combined with gene therapy have been
      recently reported to improve osteogenesis. In this study, tissue-engineered bone
      constructed by human Bone Morphogenetic Protein 4 (hBMP-4) gene-modified bone
      marrow stromal cells (bMSCs) was explored in an ectopic bone formation model in
      rabbits. METHODS: A pEGFP-hBMP-4 mammalian plasmid (EGFP: Enhanced Green
      Fluorescent Protein) was constructed by subcloning techniques. bMSCs obtained
      from rabbits were cultured and transfected with either pEGFP-hBMP-4, pEGFP or
      left uninfected in vitro. Transfer efficiency was detected through the expression
      of EGFP. Transcription of the target gene was detected by RT-PCR. Alkaline
      phosphatase (ALP) and Von Kossa tests were also conducted to explore the
      phenotypes of osteoblasts. The autologous bMSCs of the 3 groups were then
      combined with Natural Non-organic Bone (NNB), a porous hydroxyapatite implant
      with a dimension of 6 mm x 6 mm x 3 mm, at a concentration of 5 x 10(7) cells/ml.
      They were subsequently implanted into 6 rabbits subcutaneously using NNB alone as
      a blank control (6 implants per group). Four weeks after surgery, the implants
      were evaluated with histological staining and computerized analysis of new bone
      formation. RESULTS: pEGFP-hBMP-4 expression plasmid was constructed. Under
      optimal conditions, gene transfer efficiency reached more than 30%. Target gene
      transfer could strengthen the transcription of BMP-4, and increase the expression
      of ALP as well as the number of calcium nodules. In the ectopic animal model, NNB
      alone could not induce new bone formation. The new bone area formed in the bMSCs
      group was (17.2 +/- 7.1)%, and pEGFP group was (14.7 +/- 6.1)%, while pEGFP-hBMP
      4 group was (29.5 +/- 8.2)%, which was the highest among the groups (F = 7.295, P
      < 0.01). CONCLUSIONS: The mammalian hBMP-4 expression plasmid was successfully
      constructed and a comparatively high transfer efficiency was achieved. The gene
      transfer technique enhanced the expression of BMP-4 and promoted differentiation
      from bMSCs to osteoblasts. These in vivo results suggested that transfection of
      bMSCs with hBMP-4 might be a suitable method to enhance their inherent osteogenic
      capacity for bone tissue engineering applications.

PMID- 15740666
TI  - Effects of adenovirus mediated vascular endothelial growth factor gene transfer
      on reconstitution of hematopoiesis in post-bone marrow transplantation mice.
AB  - BACKGROUND: Bone marrow transplantation (BMT) conditioning procedure is
      considered as the cause of damage to bone marrow microvasculature and the delay
      of hematopoiesis recovery. However, hematopoiesis regulation post BMT by vascular
      endothelial growth factor (VEGF) has not yet been studied. In this study,
      adenovirus were used to investigate the effects of VEGF gene transfer on
      preventing damages to bone marrow microenvironment and its promotion of
      hematopoiesis in post-BMT mice. METHODS: Recombinant adenovirus (Ad)-enhanced
      green fluorescent protein (EGFP)/hVEGF165 was injected via tail vein into BALB/c
      mice undergoing syngeneic BMT. During the different phases post BMT, the
      distribution of adenovirus and the plasma levels of hVEGF were measured as well
      as the numbers of white blood cells (WBC), platelet (PLT) and red blood cells
      (RBC) in peripheral blood. At the same time, the mice were injected with Chinese
      ink via tail vein, following which the tibias were separated and were used for
      analysis of bone marrow microvasculature surface area and cellularity. RESULTS:
      Significant expression of EGFP and hVEGF was observed in multiple organs at
      different phases post BMT, and the plasma level of hVEGF was up to (866.67 +/-
      97.13) pg/ml. The recovery of WBC, PLT and RBC of the group treated with
      recombinant adenovirus Ad-EGFP/hVEGF165 were significantly more rapid than those
      of other BMT groups (P < 0.05, respectively). At the 20th day post BMT, the
      percentage of bone marrow microvasculature surface area in group treated with
      VEGF [(61.2 +/- 4.0)%] returned to normal level [(62.0 +/- 5.0)%, P > 0.05]. The
      restoration of hematopoiesis was retarded more than that of microvasculature. The
      cellularity of bone marrow in each group was still lower than that of normal
      control [(62.3 +/- 4.0)%, P < 0.05] at the 30th day post BMT, but the percentage
      in group treated with VEGF at the 20th and 30th days post BMT [(46.5 +/- 5.0)%
      and (55.1 +/- 4.5)%] exceeded those of other BMT groups (P < 0.05, respectively).
      CONCLUSION: VEGF gene transfer mediated by adenovirus may protect the
      hematopoietic microenvironment to promote the restoration of hematopoiesis in
      post-BMT mice.

PMID- 15740667
TI  - Anti-tumor effect of pEgr-interferon-gamma-endostatin gene-radiotherapy in mice
      bearing Lewis lung carcinoma and its mechanism.
AB  - BACKGROUND: Gene-radiotherapy, the combination of gene therapy and radiation
      therapy, is a new paradigm for cancer treatment. To enhance anti-tumor effect of
      gene-radiotherapy, in this study we construct a radiation-inducible dual-gene co
      expression vector pEgr-interferon (IFN)-gamma-endostatin and studied the anti
      tumor effect of pEgr-IFN-gamma-endostatin gene-radiotherapy in mice bearing Lewis
      lung carcinoma and its mechanism. METHODS: Gene recombinant technique was used to
      construct dual-gene co-expression plasmid pEgr-IFN-gamma-endostatin, and single
      gene expression plasmid pEgr-IFN-gamma and pEgr-endostatin. The plasmids packed
      by liposome were injected locally into the tumors of the mice, and the tumors
      were irradiated with 5 Gy X-ray 36 hours later. The tumor growth rate at
      different time and mean survival period of the mice were observed. Cytotoxic
      activity of splenic cytotoxic T-lymphocyte (CTL), natural killer (NK) cell and
      tumor necrosis factor (TNF)-alpha secretion activity of peritoneal macrophages of
      the mice in various groups were evaluated 15 days after irradiation. The
      intratumor micro-vessel density was evaluated by immunohistochemical staining 10
      days after irradiation. RESULTS: The tumor growth rate of the mice in dual-gene
      radiotherapy group was significantly lower than those in control group, 5 Gy
      group and single-gene-radiotherapy group at different time after gene
      radiotherapy, and the mean survival period of which was longer. Cytotoxic
      activity of splenic CTL, NK and TNF-alpha secretion activity of peritoneal
      macrophages of the mice in dual-gene-radiotherapy group were significantly higher
      than those in control group, 5 Gy X-ray irradiation group and pEgr-endostatin
      gene-radiotherapy group 15 days after irradiation. The intratumor micro-vessel
      density of the mice in dual-gene-radiotherapy group was significantly lower than
      those in control group, 5 Gy X-ray irradiation group and pEgr-IFN-gammagene
      radiotherapy group. CONCLUSION: The anti-tumor effect of dual-gene-radiotherapy
      was significantly better than that of single-gene-radiotherapy by combining the
      enhancement of anti-tumor immunologic function induced by IFN-gamma with the anti
      angiogenesis function of endostatin.

PMID- 15740668
TI  - Mutation analysis of PAX6 gene in a large Chinese family with aniridia.
AB  - BACKGROUND: Mutations in PAX6 gene have been shown to be the genetic cause of
      aniridia, which is a severe panocular eye disease characterised by iris
      hypoplasia. However, there is no study to do genetic analysis of aniridia,
      although there are several case reports in China. Here, we describe a mutation
      analysis of PAX6 in a large Chinese family with aniridia. METHODS: Genomic DNA
      from venous blood samples was prepared. Haplotype analysis was performed with two
      genetic markers (D11S904 and D11S935). Fourteen exons of the PAX6 gene were
      amplified from genomic DNA. Polymerase chain reaction (PCR) products of each exon
      were analysed by single strand conformational polymorphism (SSCP). The PCR
      products having an abnormal pattern were sequenced to confirm the mutation.
      RESULTS: Significant evidence for allele sharing in affected patients was
      detected suggesting that PAX6 mutation links to aniridia in this family. An extra
      band corresponding to exon 9 in PAX6 was found by single strand conformational
      polymorphism analysis in all the aniridia patients in this family, but not
      detected in the unaffected members. A mutation of C to T was detected by
      sequencing at the nucleotide 1080 that converts the Arg codon (CGA) to the
      termination codon (TGA). CONCLUSIONS: Aniridia is caused by a nonsense mutation
      of PAX6 gene in the large Chinese kindred. Genetic test is important to prevent
      the transmission of aniridia to their offsprings in the kindred by prenatal
      diagnosis.

PMID- 15740669
TI  - Oncolytic herpes simplex virus vectors for the treatment of human breast cancer.
AB  - BACKGROUND: Oncolytic herpes simplex virus (HSV) vectors can be used for cancer
      therapy as direct cytotoxic agents, inducers of anti-tumor immune responses, and
      as expressers of anti-cancer genes. In this study, the efficacy of HSV vectors,
      G47Delta and NV1023 were examined for the treatment of the human breast cancer.
      METHODS: Human breast cancer MDA-MB-435 cells were cultured or implanted
      subcutaneously in BALB/c nude mice. The cells or tumors were inoculated with
      G47Delta or NV1023, and cell killing or inhibition of tumor growth determined.
      Both viruses contained the LacZ gene and expression in infected cells was
      detected with X-gal histochemistry. RESULTS: G47Delta and NV1023 were highly
      cytotoxic to MDA-MB-435 cells in vitro at very low multiplicities of infection. X
      gal staining of infected tumor cells in vitro and in vivo illustrated the
      replication and spread of both viruses. G47Delta and NV1023 inoculation inhibited
      tumor growth and prolonged mouse survival. Both vectors behaved similarly.
      CONCLUSIONS: Oncolytic HSV vectors, G47Delta and NV1023, were extremely effective
      at killing human breast cancer cells in vitro and in tumor xenografts in vivo.
      This novel form of cancer therapy warrants further investigation and
      consideration of clinical application.

PMID- 15740670
TI  - Enhancing DNA vaccine potency against hantavirus by co-administration of
      interleukin-12 expression vector as a genetic adjuvant.
AB  - BACKGROUND: The heavy incidence and mortality of hemorrhagic fever with renal
      syndrome, as well as no specific drugs in curing the disease, clearly indicate
      the need for development of the more effective hantavirus vaccine. Refining the
      DNA vaccination strategy to elicit more clinically efficacious immune responses
      is now under intensive investigation. In the present study, we examined the
      effects of using an interleukin-12 expression plasmid as a genetic adjuvant to
      enhance the immune responses induced by a DNA vaccine based on the S gene
      encoding nucleocapsid protein against hantavirus. METHODS: BALB/c mice were
      immunized three times by intramuscular inoculations of DNA vaccine encoding of
      hantanvirus nucleocapsid protein alone or in combination with a plasmid
      expressing murine interleukin-12 (pcIL-12). Booster immunizations were employed 2
      times at 2-week interval. To evaluate the humoral and cellular immune responses,
      antigen-specific lymphocyte proliferation and antibody production were assayed by
      MTT method and ELISA respectively. The level of interleukin-4 and interferon
      gamma in the splenic lymphocytic cultured supernatant were detected with ELISA
      kit at day 5, 10, 17, 35 and 42 after primary immunization. RESULTS: Antigen
      specific IgG antibodies was increased markedly at day 17 in the experiment groups
      and reached a plateau after day 35. As pcIL-12 co-injected, a significant
      inhibition of antigen-specific IgG levels was displayed over the period and the
      antibody mean titre was decreased to only about 1:50 at day 42 after primary
      immunization, significantly lower than the group immunized with pcDNA3.1 + S
      alone, in which the mean titre was about 1:70. Interferon-gamma was increased
      remarkably by the co-injection of pcIL-12 compared with the injection of pcDNA3.1
      + S alone. However, the production of interleukin-4 was inhibited by pcIL-12 co
      injection. Furthermore, pcIL-12 co-injection efficiently enhanced antigen
      specific lymphocyte proliferation. CONCLUSION: Humoral and cytokine responses
      elicited by pcDNA3.1 + S inoculation can be modulated by co-inoculation with pcIL
      12 and efficiently induced Th1-dominant immune responses.

PMID- 15740671
TI  - Relationship between tunnel widening and different rehabilitation procedures
      after anterior cruciate ligament reconstruction with quadrupled hamstring
      tendons.
AB  - BACKGROUND: It has been demonstrated that bone tunnel widening could appear after
      knee anterior cruciate ligament (ACL) reconstruction, especially for those
      patients whose ruptured ACL were reconstructed with semitendinosus and gracilis
      tendons. Many factors can influence the extent of tunnel widening. Few studies
      have investigated the relationship between bone tunnel widening and
      rehabilitation procedures. This research was carried out to find the
      rehabilitation procedures' influence on the tibial bone tunnel widening after ACL
      reconstruction. METHODS: Sixty-five cases, whose ACL reconstructions were done
      using quadrupled semitendinosus and gracilis tendons, were divided into two
      groups. Group A had 33 cases, 19 men, 14 women, averaged (31.2 +/- 12.4) years
      old, only ACL reconstruction was done using Paessler's technique, and aggressive
      rehabilitation procedure was used for function recovery post operation. Group B
      had 32 cases, 20 men, 12 women, averaged (30.3 +/- 10.3) years old. Except for
      ACL reconstruction, every patient in group B accepted meniscus repair using re
      fixation methods or cartilage repair using microfracture technique, conservative
      rehabilitation procedure was used post operation. Six months post operation,
      standard posterior-anterior radiographic plates were taken for each case,
      CorelDRAW 8.0 software was used to digitize all X-ray plates and measure the
      upper, middle and lower parts of the tibial tunnel. Magnification effect of X-ray
      plates was taken out after measurement. RESULTS: Six months after ACL
      reconstruction the tibial tunnel widening of the upper, middle and lower parts on
      both the posterior-anterior and lateral X-ray plates in Group A with aggressive
      rehabilitation procedure was much more serious than in Group B with conservative
      rehabilitation. KT-1000 knee stability measurement and clinical manifestation
      showed no difference between the two groups. CONCLUSIONS: Rehabilitation
      procedure after ACL reconstruction is one of the reasons for tunnel widening. It
      not only can directly influence the function recovery of ACL reconstructed knee,
      but also perhaps indirectly influence the function recovery and long-term
      clinical result of the operated knee by influencing the tunnel widening.

PMID- 15740672
TI  - Present epidemic situation of liver alveolar echinococcosis in Gansu Province,
      China.

PMID- 15740673
TI  - Involvement of the p38 mitogen-activated protein kinase signal transduction
      pathway in burns-induced lung injury.

PMID- 15740675
TI  - Histopathological changes of free buccal mucosa and colonic mucosa grafts after
      translation to dog bladder.

PMID- 15740674
TI  - Effects of mifepristone on the proliferation, apoptosis and cis
      diamminedichloroplatinum sensitivity of cultured chemoresistant human ovarian
      cancer cells.

PMID- 15740676
TI  - Inhibitory effects of reserpine and carbonyl cyanide m-chloro-phenylhydrazone on
      fluoroquinolone resistance of Acinetobacter baumannii.

PMID- 15740677
TI  - Surgical treatment of double outlet ventricle: report on 72 cases.

PMID- 15740678
TI  - Intraspinal clear cell meningioma: a case report.

PMID- 15740679
TI  - Restoration of severe hypodontia associated with microdontia by using an
      overdenture: a clinical report.

PMID- 15740680
TI  - Dietary protein intake during the oestrous cycle does not alter the ovulation
      rate in gilts.
AB  - The effect of protein intake on ovulation rate was investigated in cross-bred
      gilts. On Day 14 of the third oestrous cycle, luteolysis was induced by injection
      of an analogue of prostaglandin F(2alpha). The ovulation rate was recorded when
      gilts were killed on Day 27. In the first experiment, nutritional treatment was
      applied from Day 14 to Day 27. Gilts were fed diets providing the same amount of
      digestible energy, but containing either a low, medium or high amount of dietary
      protein. Protein restriction linearly decreased plasma concentrations of urea (P
      < 0.001) and had no effect on plasma concentrations of insulin-like growth factor
      I and leptin measured at Day 27 (P > 0.1). Protein restriction did not influence
      ovulation rate (mean (+/- s.e.m.) 17.0 +/- 0.4; P > 0.1). In the second
      experiment, the nutritional treatment was applied from Day 5 until Day 27. Gilts
      received the same amount of digestible energy and either a low or a high amount
      of protein, as in Experiment 1. A third group of gilts received the high amount
      of protein and also more digestible energy. The ovulation rate did not differ
      between the three groups of gilts. These data indicate no effect of short-term
      dietary protein restriction on ovulation rate in cyclic gilts.

PMID- 15740681
TI  - Induced parthenogenetic activation of oocytes of the marsupial Sminthopsis
      macroura.
AB  - Maturation of marsupial oocytes in vitro, an important step in the analysis of
      early developmental events, has a low success rate and results from the
      artificial activation of oocytes, which may not include nuclear maturation. In
      Sminthopsis macroura, 24-h culture of advanced antral follicles in medium
      containing 10 microg mL(-1) porcine pituitary luteinising hormone (LH) yielded
      60% of mature polarised oocytes with the first polar body; follicles cultured in
      medium without LH yielded only immature oocytes. Parthenogenetic activation of
      follicular, oviducal or uterine oocytes occurred when a two-step protocol was
      used. Sixty-one oocytes, exposed to 10 microm calcium ionophore A23187 for 10 min
      followed by 10 microg mL(-1) cycloheximide (protein synthesis inhibitor) for 5 h
      and then cultured for 20-24 h, were scored for signs of activation, namely
      extrusion of the second polar body and formation of the pronucleus. In each of 43
      oocytes (70%), the extruded second polar body was present. Sixteen oocytes were
      analysed on slides after fixation and staining and, in 13 oocytes (81%) in this
      group, the female pronucleus was visible. No activation occurred following
      incubation of oocytes in medium containing Sr(2+) for 5 h (n = 14), 8% ethyl
      alcohol solution for 8 or 12 min (n = 13) or 10 microm calcium ionophore A23187
      (n = 13) for 10-20 min followed by culture for 20-24 h.

PMID- 15740682
TI  - Developmental competence in vitro and in vivo of cryopreserved, hatched
      blastocysts from the dromedary camel (Camelus dromedarius).
AB  - The present paper describes experiments designed to investigate methods for
      cryopreserving embryos from dromedary camels. Because preliminary studies had
      shown ethanediol to be the best cryoprotectant to use for camel embryos, the
      current experiments were performed to determine the minimum exposure time to 1.5
      m ethanediol required to achieve cryoprotection. The uteri of 30 donor camels
      were flushed non-surgically 8 days after mating. Embryos were recovered and 158
      were assigned to one of three groups, which were exposed to 1.5 m ethanediol for
      either 10 min (n = 67), 5 min (n = 51) or 1 min (n = 40). Embryos were
      subsequently thawed and rehydrated by expelling either directly into holding
      medium (HM; HEPES-buffered Tyrode's medium containing sodium lactate and 3 mg mL(
      1) bovine serum albumin, 10% fetal calf serum, 100 IU mL(-1) penicillin G, 100
      microg mL(-1) streptomycin and 25 microg mL(-1) amphotercin B) or initially into
      HM containing 0.2 m sucrose for 5 or 10 min. The survival rate of all embryos
      immediately post-thawing, as judged by the morphological appearance of the
      embryos, was high (91%), but was greatly reduced after 2 h culture (59%). Ninety
      two embryos were transferred to recipient camels resulting in 18 viable fetuses
      (1 min ethanediol exposure, n = 1/15; 5 min ethanediol exposure, n = 3/34; 10 min
      ethanediol exposure, n = 14/43). Of the embryos rehydrated directly in HM, six of
      65 resulted in viable fetuses and those rehydrated initially in 0.2 m sucrose for
      5 or 10 min resulted in nine of 47 and three of 46 fetuses respectively. From
      these experiments, we conclude that camel embryos can be cryopreserved using
      ethanediol as a cryoprotectant when the embryos are cooled slowly (to 33 degrees
      C) before being plunged into liquid nitrogen for storage.

PMID- 15740683
TI  - Parallel changes between the percentage of fetal pituitary cells immunoreactive
      to oestrogen receptor alpha and the concentration of 17beta-oestradiol in fetal
      and maternal plasma during gestation in sheep.
AB  - The present study was designed to investigate the relationship between fetal
      sheep pituitary oestrogen receptor (ER) alpha expression and changes in fetal and
      maternal plasma 17beta-oestradiol (E2) concentrations during gestation. The
      results revealed that immunoreactivity for ER was located in the nuclei and
      distributed throughout the fetal pituitary gland during gestation. The percentage
      of ERalpha-positive cells was approximately 2% of the total cell population in
      female fetuses at Day 60 of gestation, increased to approximately 7% and 13% of
      the total cell population at Days 90 and 120 of gestation, respectively, and then
      declined to approximately 10% at birth. The fetal plasma E2 concentrations were
      approximately 19 and 71 pg mL(-1) at Days 90 and 120 of gestation, respectively,
      and decreased to 22 pg mL(-1) after birth. In male fetuses, plasma E2
      concentrations and the percentage of ERalpha-positive cells were similar to
      values in female fetuses throughout gestation, except on Day 120 when the plasma
      E2 level in female fetuses was significantly higher than in male fetuses. These
      data demonstrate that changes in the percentage of fetal pituitary ERalpha
      positive cells parallel fetal plasma E2 concentrations throughout gestation.

PMID- 15740684
TI  - Comparison of glucose metabolism in in vivo- and in vitro-matured tammar wallaby
      oocytes and its relationship to developmental potential following
      intracytoplasmic sperm injection.
AB  - Although marsupial oocytes undergo nuclear maturation in vitro, there is, at
      present, no indication of their developmental potential, largely owing to the
      lack of in vitro fertilisation and related technologies for marsupials. Glucose
      metabolism has proven a useful indicator of oocyte cytoplasmic maturation and
      developmental potential in several eutherian species. Therefore, the aims of the
      present study were to compare: (1) the rates of glycolysis and glucose oxidation
      in immature, in vitro-matured and in vivo-matured tammar wallaby oocytes; and (2)
      the metabolic rate of individual oocytes with their ability to form pronuclei
      after intracytoplasmic sperm injection. The rates of glycolysis measured in
      immature (2.18 pmol oocyte(-1) h(-1)), in vitro- matured (0.93 pmol oocyte(-1) h(
      1)) and in vivo-matured tammar wallaby oocytes (0.54 pmol oocyte(-1) h(-1)) were
      within a similar range to values obtained in eutherian species. However, unlike
      the trend observed in eutherian oocytes, the glycolytic rate was significantly
      higher in immature oocytes compared with either in vivo- or in vitro-matured
      oocytes (P < 0.001) and significantly higher in in vitro-matured oocytes compared
      with in vivo-matured oocytes (P < 0.001). No relationship was identified between
      glucose metabolism and the developmental capacity of oocytes after
      intracytoplasmic sperm injection when assessed after 17-19 h. Oocytes that became
      fertilised (two pronuclei) or activated (one or more pronucleus) were not
      distinguished from others by their metabolic rates. Longer culture after
      intracytoplasmic sperm injection (e.g. blastocyst stage) may show oocyte glucose
      metabolism to be predictive of developmental potential; however, culture to the
      single-cell stage did not reveal any significant differences in normally
      developing embryos.

PMID- 15740686
TI  - Nutrition and colostrum production in sheep. 1. Metabolic and hormonal responses
      to a high-energy supplement in the final stages of pregnancy.
AB  - We tested the hypothesis that supplementation with cracked maize during the last
      week of pregnancy would provide ewes with a substrate for glucose and enhance the
      synthesis of lactose and, consequently, their production of colostrum. Thirty
      single- and 30 twin-bearing ewes were fed lucerne hay and half of each group was
      supplemented daily with 0.75 kg per head cracked maize during the last week of
      pregnancy. Colostrum production and the endocrine patterns in the animals were
      investigated. Supplementation with maize more than doubled the mass of colostrum
      available at birth in unsupplemented ewes: 339 v. 145 g in single-bearing ewes
      and 536 v. 197 g in twin-bearing ewes (P < 0.001). The total colostrum produced
      in the 10 h after birth was also significantly increased by supplementation: 730
      v. 475 g in single-bearing ewes and 1259 v. 631 g in twin-bearing ewes (P <
      0.01). The colostrum in the supplemented ewes was also more liquid with a
      viscosity score of 5.8 compared with 5.7 and 4.5 in unsupplemented single- and
      twin-bearing ewes (P < 0.01). Supplemented ewes had higher concentrations of
      lactose in their colostrum at parturition (2.6% v. 1.8% in single-bearing ewes
      and 2.5% v. 1.4% in twin-bearing ewes; P < 0.01). The plasma concentrations of
      progesterone and growth hormone in supplemented ewes were lower, whereas those of
      IGF-I and insulin were higher, all consistent with a higher capacity to produce
      colostrum. It is concluded that a high-energy supplement, like maize, fed to ewes
      in the last week of gestation increases their capacity to produce colostrum for
      their lambs, particularly for ewes bearing twins.

PMID- 15740685
TI  - Effect of graded hypoxia on activin A, prostaglandin E2 and cortisol levels in
      the late-pregnant sheep.
AB  - The aim of the present study was to determine whether activin A concentrations
      are dependent on feto-placental oxygen availability and to investigate the
      temporal relationship of activin A with prostaglandin (PG) E(2) and cortisol.
      Nine fetal sheep (six hypoxic and three control) were instrumented and
      catheterised at 0.8 gestation. Reduced uterine blood flow was used to achieve
      three levels of hypoxia (mild = fetal SaO(2) 40-50%; moderate = fetal SaO(2) 30
      40%; severe = fetal SaO(2) 20-30%), for 4 h on 3 consecutive days. Activin A,
      PGE(2) and cortisol levels were determined in maternal and fetal blood and
      amniotic fluid. Moderate and severe hypoxia produced a significant (P < 0.05)
      increase in fetal plasma activin A concentrations. The amniotic fluid activin A
      concentrations were 15-fold higher than those in the fetal circulation, but were
      unchanged by hypoxia. The fetal PGE(2) response reflected the degree of hypoxia
      over the 3 days, with moderate and severe hypoxia producing a significant (P <
      0.05) increase in PGE(2) concentrations. Fetal plasma cortisol concentrations
      were increased ( P < 0.05) during all levels of hypoxia. Fetal arterial activin A
      was increased in response to moderate and severe hypoxia, but levels were not
      maintained over the hypoxic period. The increases in activin A and cortisol
      concentrations preceded the increase in PGE(2).

PMID- 15740687
TI  - Nutrition and colostrum production in sheep. 2. Metabolic and hormonal responses
      to different energy sources in the final stages of pregnancy.
AB  - Lupins and maize, with similar concentrations of metabolisable energy, should
      produce similar responses in colostrum production at parturition when fed during
      the last week of pregnancy, but, in the present study, we tested the proposal
      that the physical form of whole lupins would restrict intake and, therefore, the
      response compared with cracked lupins or maize. Fifty-five twin-bearing ewes were
      divided into four groups: in the last 15 days of pregnancy, 14 were fed whole
      lupins, 13 were fed cracked lupins, 14 were fed cracked maize and 14 received no
      supplement. The cracked supplements were fed in increasing amounts for 6 days to
      avoid acidosis. The whole lupins were fed only from Day -8. All supplementary
      grains increased the intake of metabolisable energy by >35%, but only ewes eating
      maize accumulated significantly more colostrum at parturition: control, 207 g;
      cracked maize, 452 g; cracked lupins, 206 g; whole lupins, 231 g (P < 0.05).
      Plasma urea concentrations were extremely high (approximately 10 mmol L(-1)) for
      both groups eating lupins and approximately double those of control ewes or those
      receiving maize ( P < 0.05). We conclude that gut distention is not a cause of a
      poor response to lupins, but the ammonia associated with near-toxic
      concentrations of plasma urea may be affecting the production of colostrum.

PMID- 15740688
TI  - Founders' Lecture. Human spermatozoa: fruits of creation, seeds of doubt.
AB  - Deoxyribonucleic acid damage in the male germline is associated with defective
      fertilisation, impaired embryonic development, reduced implantation, abortion and
      childhood disease. Oxidative stress and the retention of excess residual
      cytoplasm by the spermatozoa are frequently associated with the induction of such
      damage. The redox cycling of xenobiotics by oxido-reductases in the germline, the
      patient's age, the incidence of genital tract infections and Sertoli cell
      dysfunction are all possible contributors to DNA damage in germ cells. Collateral
      peroxidation of unsaturated fatty acids in the sperm plasma membrane generally
      ensures that spermatozoa experiencing severe oxidative DNA damage cannot
      participate in the process of fertilisation. The adaptive termination of
      pregnancy through the selective vulnerability of genes involved in placentation
      may also help prevent the vertical transmission of damaged DNA. However, the
      ultimate safeguard against this form of damage will be to understand the
      biochemical basis of oxidative stress in human spermatozoa, so that the
      underlying causative mechanisms can be addressed in a logical manner.

PMID- 15740689
TI  - Effect of the oxidative phosphorylation uncoupler 2,4-dinitrophenol on hypoxia
      inducible factor-regulated gene expression in bovine blastocysts.
AB  - In cattle embryos, development to the blastocyst stage is improved in the
      presence of 10 micro;m 2,4-dinitrophenol (DNP), an uncoupler of oxidative
      phosphorylation, coincident with an increase in glycolytic activity following
      embryonic genome activation. The present study examined redox-sensitive gene
      expression and embryo development in response to the addition of DNP post
      compaction. 2,4-Dinitrophenol increased the expression of hypoxia-inducible
      factor 1alpha and 2alpha (HIF1alpha, HIF2alpha) mRNA. Although HIF1alpha protein
      remained undetectable in bovine blastocysts, HIF2alpha protein was localised
      within the nucleus of trophectoderm and inner cell mass (ICM) cells of
      blastocysts cultured in the presence or absence of DNP, with a slight increase in
      staining evident within the ICM in blastocysts cultured in the presence of DNP.
      However, the expression of GLUT1 and VEGF mRNA, genes known to be regulated by
      HIFs, was unaffected by the addition of DNP to the culture. Although the
      development of Grade 1 and 2 blastocysts was unaltered by the addition of DNP
      post compaction in the present study, a significant increase in the proportion of
      ICM cells was observed. Results indicate that 10 microm DNP improves the quality
      of bovine embryos, coincident with increased HIF2alpha protein localisation
      within ICM cells and increased HIFalpha mRNA levels. Therefore, the results
      demonstrate redox-regulated expression of HIF2.

PMID- 15740690
TI  - Cloned horse pregnancies produced using adult cumulus cells.
AB  - The objectives of the present study were to: (1) clone horses using adult cumulus
      cells; and (2) determine whether the cumulus cell donor affected the outcome. In
      vivo-matured cumulus-oocyte complexes were obtained using transvaginal ultrasound
      guided follicle aspiration; oocytes were used as cytoplasts, whereas cumulus
      cells (from one of three different mares) were used as donor cells. Immediately
      following nuclear transfer and activation procedures, cloned embryos were
      transferred surgically to the oviduct of recipient mares (n = 2-5 embryos per
      recipient) that had ovulated within 24 h prior to the transfer. An initial
      pregnancy examination was performed between Days 14 and 16 (Day 0 = surgery);
      subsequent examinations were then performed every 7-10 days. A total of 136
      follicles were aspirated in 96 mares, from which 72 oocytes were recovered (53%).
      Sixty-two cloned embryos were transferred to recipient mares, which resulted in
      seven (11.3%) ultrasonographically detectable conceptuses between Days 14 and 16.
      All seven conceptuses were lost spontaneously between Days 16 and 80. Cumulus
      cells from Mare 160 tended (P = 0.08) to result in a higher embryo survival rate
      than cumulus cells from Mare 221 (4/17 v. 1/25 respectively). To our knowledge,
      this is the first report documenting the establishment of cloned equine
      pregnancies derived from adult cumulus cells.

PMID- 15740691
TI  - Head area measurements of dead, live, X- and Y-bearing bovine spermatozoa.
AB  - The head area of bull spermatozoa was measured after viability and acrosome
      staining using trypan blue and Giemsa stains, followed by X- and Y-chromosome
      specific fluorescence in situ hybridisation (FISH). The former staining made
      possible the categorisation of cells according to morphology and membrane
      integrity, whereas the latter allowed distinction of spermatozoa bearing X- and Y
      chromosomes. Individual spermatozoa could be followed during the consecutive
      steps of staining, measurement and FISH. Using a high-resolution digital imaging
      system and measurement software, the head area of more than 3000 cells of five
      bulls was determined precisely. In all bulls, morphologically normal, viable
      cells with intact acrosomes were significantly smaller than dead cells with
      damaged acrosomes. No significant difference in the head area between X- and Y
      chromosome-bearing viable, acrosome-intact spermatozoa was found in individual
      bulls. However, significant between-bull differences were detected in all cell
      categories.

PMID- 15740692
TI  - Expression of endothelial and inducible nitric oxide synthases is modulated in
      the endometrium of cyclic and early pregnant mares.
AB  - The expression of the endothelial and inducible nitric oxide synthases (eNOS and
      iNOS, respectively) was examined in the endometrium of cyclic and pregnant mares
      by real-time polymerase chain reaction and immunohistology. The concentration of
      eNOS mRNA varied throughout the oestrous cycle, with significantly higher
      transcripts on Day 5 of the oestrous cycle (P < 0.05), whereas iNOS transcription
      did not change significantly over time (P > 0.05). In early pregnant mares both
      eNOS and iNOS mRNA increased between Days 12 and 15 (P < 0.05). In cyclic mares,
      eNOS protein was detected immunocytochemically in endometrial epithelia, the
      basement membrane, the endothelial layer and smooth muscle cells of the
      vasculature. Using immunocytochemical methods, iNOS protein was undetectable in
      the endometrium of cyclic mares but could be demonstrated in pregnant mares.
      Endometrial epithelia of pregnant mares were immunopositive for both proteins
      with a more intense labelling for iNOS. Thus, the present study describes for the
      first time the modulation and spatial distribution of eNOS and iNOS expression
      during the oestrous cycle and early pregnancy, suggesting that ovarian steroids
      are differently involved in the regulation of each NOS. Localisation of eNOS
      protein in endometrial epithelia and various vascular components indicates that
      this isoform may be involved in the regulation of endometrial cyclicity. The
      presence and increase of both forms of NOS during early gestation suggest a role
      for them in the control of endometrial vascular bed and glandular activity to
      provide a suitable microenvironment for successful pregnancy.

PMID- 15740693
TI  - Influence of hormone environment and donor age on cryopreserved common wombat
      (Vombatus ursinus) ovarian tissue xenografted into nude mice.
AB  - Developmentally competent oocytes can be collected from xenografted ovarian
      tissues; however, optimal xenograft conditions need to be established for this
      technique to be of use in assisted reproduction. In the present study, common
      wombat ovarian tissue was xenografted under the kidney capsule of nude mice to
      clarify the role of recipient gonadal status and donor tissue age on graft
      establishment, follicle development and oocyte recovery. Eighty-nine per cent of
      all grafts were recovered; of these, 78% contained growing follicles. In female
      graft recipients, follicle development to the antral stage occurred earlier in
      ovariectomised recipients compared with intact graft recipients. Similarly,
      follicle development occurred earlier in recipients of pouch young ovarian tissue
      grafts when compared with subadult xenografts. Follicle development proceeded to
      the antral stage in subadult grafts placed under the kidney capsule of male
      recipient mice, albeit at a slower rate than subadult grafts placed in female
      recipients. Oocytes were collected from grafts placed in female and male
      recipients, but no mature oocytes were observed at the time of collection, nor
      could these oocytes be matured in vitro. The present study demonstrated that
      common wombat pouch young tissue xenografted to female recipient mice, and
      subadult ovarian tissue xenografted to male recipient mice, can develop to the
      antral stage and can therefore facilitate oocyte collection. However, mature
      oocytes were not obtained using the current protocol.

PMID- 15740695
TI  - The role of animal studies in supporting human assisted reproductive technology.
AB  - Although average success rates of human IVF have increased progressively during
      the past two decades, the efficiency of this technique, based on each embryo
      produced or transferred, is still low. High success rates are usually achieved by
      transferring several embryos to the patient, which is often associated with
      multiple pregnancies. The quality of in vitro produced embryos is a major area
      that needs attention. Because there is no in vivo database for human embryos, the
      properties of normal embryos are not known, and so it is difficult to know how to
      improve quality and viability. In addition, selection of the most viable embryos
      for transfer is a rather subjective process. The origins of human assisted
      reproductive technology (ART) are based on animal ART; however, the two areas of
      research (animal and human ART) appear to have become disconnected. Re
      examination of progress in animal ART could help improve human embryo quality and
      thereby assist efforts to sustain high pregnancy rates with only one or two
      embryos transferred. Some key areas in which animal ART can help guide progress
      in human ART are discussed.

PMID- 15740694
TI  - Distribution of aromatase activity in brain and peripheral tissues of male sheep:
      effect of nutrition.
AB  - Conversion of testosterone to oestradiol plays a major role in the feedback
      inhibition of gonadotrophin secretion in male sheep but little is known of the
      distribution or control of aromatase activity among central and peripheral
      tissues. Changes in activity at those sites may mediate alterations in the
      effectiveness of negative feedback following, for example, a change in nutrition.
      Using a tritiated-water assay, we quantified aromatase in several tissues in
      mature male sheep, assessed their contribution to oestradiol production, and
      tested whether activity at each site was affected by a nutritional treatment that
      stimulates gonadotrophin secretion. Among the brain tissues, the preoptic area
      had the highest concentration of activity, followed by the hypothalamus, amygdala
      and cortex. Among the peripheral tissues, liver and testis had the highest
      activity and, due to their mass, they are the major sources of circulating
      oestradiol. Pituitary, muscle, kidney and adipose tissues had very low aromatase
      levels. The nutritional stimulus increased activity in testis but not in liver or
      brain. We conclude that changes in aromatase activity do not mediate the effects
      of nutrition on steroid feedback, but aromatisation in testis, liver and brain is
      important in the endocrine regulation of reproduction in the mature ram.

PMID- 15740696
TI  - Genetics and imaging to assess oocyte and preimplantation embryo health.
AB  - Two major criteria are currently used in human assisted reproductive technologies
      (ART) to evaluate oocyte and preimplantation embryo health: (1) rate of
      preimplantation embryonic development; and (2) overall morphology. A major gene
      that regulates the rate of preimplantation development is the preimplantation
      embryo development (Ped) gene, discovered in our laboratory. In mice, presence of
      the Ped gene product, Qa-2 protein, results in a fast rate of preimplantation
      embryonic development, compared with a slow rate of preimplantation embryonic
      development for embryos that are lacking Qa-2 protein. Moreover, mice that
      express Qa-2 protein have an overall reproductive advantage that extends beyond
      the preimplantation period, including higher survival to birth, higher
      birthweight, and higher survival to weaning. Data are presented that suggest that
      Qa-2 increases the rate of development of early embryos by acting as a cell
      signalling molecule and that phosphatidylinositol-32 kinase is involved in the
      cell-signalling pathway. The most likely human homologue of Qa-2 has recently
      been identified as human leukocyte antigen (HLA)-G. Data are presented which show
      that HLA-G, like Qa-2, is located in lipid rafts, implying that HLA-G also acts
      as a signalling molecule. In order to better evaluate the second criterion used
      in ART (i.e. overall morphology), a unique and innovative imaging microscope has
      been constructed, the Keck 3-D fusion microscope (Keck 3DFM). The Keck 3DFM
      combines five different microscopic modes into a single platform, allowing multi
      modal imaging of the specimen. One of the modes, the quadrature tomographic
      microscope (QTM), creates digital images of non-stained transparent cells by
      measuring changes in the index of refraction. Quadrature tomographic microscope
      images of oocytes and preimplantation mouse embryos are presented for the first
      time. The digital information from the QTM images should allow the number of
      cells in a preimplantation embryo to be counted non-invasively. The Keck 3DFM is
      also being used to assess mitochondrial distribution in mouse oocytes and embryos
      by using the k-means clustering algorithm. Both the number of cells in
      preimplantation embryos and mitochondrial distribution are related to oocyte and
      embryo health. New imaging data obtained from the Keck 3DFM, combined with
      genetic and biochemical approaches, have the promise of being able to distinguish
      healthy from unhealthy oocytes and embryos in a non-invasive manner. The goal is
      to apply the information from our mouse model system to the clinic in order to
      identify one and only one healthy embryo for transfer back to the mother
      undergoing an ART procedure. This approach has the potential to increase the
      success rate of ART and to decrease the high, and undesirable, multiple birth
      rate presently associated with ART.

PMID- 15740697
TI  - Role of the mitochondrial genome in assisted reproductive technologies and
      embryonic stem cell-based therapeutic cloning.
AB  - Mitochondria play a pivotal role in cellular metabolism and are important
      determinants of embryonic development. Mitochondrial function and biogenesis rely
      on an intricate coordination of regulation and expression of nuclear and
      mitochondrial genes. For example, several nucleus-derived transcription factors,
      such as mitochondrial transcription factor A, are required for mitochondrial DNA
      replication. Mitochondrial inheritance is strictly maternal while paternally
      derived mitochondria are selectively eliminated during early embryonic cell
      divisions. However, there are reports from animals as well as human patients that
      paternal mitochondria can occasionally escape elimination, which in some cases
      has led to severe pathologies. The resulting existence of different mitochondrial
      genomes within the same cell has been termed mitochondrial heteroplasmy. The
      increasing use of invasive techniques in assisted reproduction in humans has
      raised concerns that one of the outcomes of such techniques is an increase in the
      incidence of mitochondrial heteroplasmy. Indeed, there is evidence that
      heteroplasmy is a direct consequence of ooplasm transfer, a technique that was
      used to 'rescue' oocytes from older women by injecting ooplasm from young
      oocytes. Mitochondria from donor and recipient were found in varying proportions
      in resulting children. Heteroplasmy is also a byproduct of nuclear transfer, as
      has been shown in studies on cloned sheep, cattle and monkeys. As therapeutic
      cloning will depend on nuclear transfer into oocytes and the subsequent
      generation of embryonic stem cells from resulting blastocysts, the prospect of
      mitochondrial heteroplasmy and its potential problems necessitate further studies
      in this area.

PMID- 15740698
TI  - Quantitative expression analysis of blastocyst-derived gene transcripts in
      preimplantation developmental stages of in vitro-produced bovine embryos using
      real-time polymerase chain reaction technology.
AB  - The main objective of the present study was to analyse the quantitative
      expression pattern of genes from a subtracted blastocyst transcriptome throughout
      the preimplantation developmental stages of in vitro-produced bovine oocytes and
      embryos. For this purpose, Day 5 morula (M) cDNAs were subtracted from Day 7
      blastocyst (B) cDNAs (B-M) and used to establish a B-M subtracted cDNA library,
      as reported previously. From the total generated clones, 19 were analysed
      quantitatively. The mRNA samples isolated from pools of immature oocytes (n =
      150), mature oocytes (n = 150) and two-cell (n = 80), four-cell (n = 40), eight
      cell (n = 20), morula (n = 6) and blastocyst (n = 3) embryos were reverse
      transcribed and subjected to real-time polymerase chain reaction (PCR) using
      sequence-specific primers and SYBR green as the DNA dye. A relative standard
      curve method was used to analyse the real-time data taking the morula stage as a
      calibrator. Applying suppression subtractive hybridisation (SSH), a total of 71
      clones, which represent 33 different expressed sequence tags, were generated and
      available for analysis. Most transcripts were analysed for the first time in
      bovine embryogenesis. The real-time PCR has validated the results of SSH
      positively for 84% (16/19) of transcripts, whereas 16% (3/19) showed deviation in
      the expression pattern from the one seen during SSH. Several transcript-specific
      expression patterns were observed for genes that play decisive roles in bovine
      embryogenesis. In addition to identification, accurately quantifying the
      expression profiles of transcripts during development will pave the way towards
      understanding the molecular mechanisms of embryogenesis and their potential role
      in early embryo development. Most importantly, the present study has contributed
      to the enrichment of bovine embryo gene collection by generating new transcripts
      involved in bovine embryo development.

PMID- 15740699
TI  - Gene expression analysis of the pro-oestrous-stage rat uterus reveals neuroligin
      2 as a novel steroid-regulated gene.
AB  - In the present study, differential gene expression in the uteri of ovariectomised
      (OVX) and pro-oestrous rats (OVX v. pro-oestrus pair) was investigated using cDNA
      expression array analysis. Differential uterine gene expression in OVX rats and
      progesterone (P(4))-injected OVX rats (OVX v. OVX + P(4) pair) was also examined.
      The uterine gene expression profiles of these two sets of animals were also
      compared for the effects of P(4) treatment. RNA samples were extracted from
      uterine tissues and reverse transcribed in the presence of [alpha(32)P]-dATP.
      Membrane sets of rat arrays were hybridised with cDNA probe sets. Northern blot
      analysis was used to validate the relative gene expression patterns obtained from
      the cDNA array. Of the 1176 cDNAs examined, 23 genes showed significant (>two
      fold) changes in expression in the OVX v. pro-oestrus pair. Twenty of these genes
      were upregulated during pro-oestrus compared with their expression in the OVX rat
      uterus. In the OVX v. OVX + P(4) pair, 22 genes showed significant (>two-fold)
      changes in gene expression. Twenty of these genes were upregulated in the OVX +
      P(4) animals. The genes for nuclear factor I-XI, afadin, neuroligin 2, semaphorin
      Z, calpain 4, cyclase-associated protein homologue, thymosin beta-4X and p8 were
      significantly upregulated in the uteri of the pro-oestrus and OVX + P(4) rats of
      both experimental pairs compared with the OVX rat uteri. These genes appear to be
      under the control of P(4). One of the most interesting findings of the present
      study is the unexpected and marked expression of the neuroligin 2 gene in the rat
      uterus. This gene is expressed at high levels in the central nervous system and
      acts as a nerve cell adhesion factor. According to Northern blot analysis,
      neuroligin 2 gene expression was higher during the pro-oestrus and metoestrus
      stages than during the oestrus and dioestrus stages of the oestrous cycle. In
      addition, neuroligin 2 mRNA levels were increased by both 17beta-oestradiol
      (E(2)) and P(4), although P(4) administration upregulated gene expression to a
      greater extent than injection of E(2). These results indicate that neuroligin 2
      gene expression in the rat uterus is under the control of both E(2) and P(4),
      which are secreted periodically during the oestrous cycle.

PMID- 15740700
TI  - Relationship between DNA fragmentation and nuclear status of in vitro-matured
      porcine oocytes: role of cumulus cells.
AB  - The present study was conducted to investigate the effects of the attachment of
      cumulus cells to oocytes and coculture with cumulus cells during maturation
      culture on the nuclear status and DNA fragmentation of porcine denuded oocytes
      (DOs). In the first experiment, cumulus cells were removed from cumulus-oocyte
      complexes (COCs) at 0, 8, 16, 24 or 32 h after the onset of maturation culture
      and the DOs were then cultured in their original droplets until 42 h of culture
      was reached. In the second experiment, all COCs were denuded before the onset of
      culture and the DOs were cocultured with their removed cumulus cells. The DOs
      were transferred into fresh medium at 0, 8, 16, 24 or 32 h after the onset of
      coculture with cumulus cells and then cultured until 42 h of culture was reached.
      After culture, DNA fragmentation and the nuclear status of oocytes were examined
      using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin
      nick end-labelling (TUNEL) method. When the DOs were returned to the same
      droplets after removal of the cumulus cells, the removal of the cumulus cells
      after 16 h of culture significantly decreased the proportion of oocytes remaining
      at the germinal vesicle (GV) stage. However, coculture treatment of DOs in the
      presence of their removed cumulus cells had no significant effects on the GV
      breakdown (GVBD) of oocytes. There were no significant differences in the
      proportion maturing to MII oocytes among the groups following removal of cumulus
      cells after the onset of maturation culture; however, DOs cocultured with cumulus
      cells until the end of maturation culture exhibited an increased maturation rate
      compared with DOs cocultured for 8 and 16 h. The total proportion of TUNEL
      positive oocytes of oocytes remaining at the GV stage was higher than that of
      oocytes reaching other stages, irrespective of the removal of cumulus cells and
      coculture treatments. However, coculture for more than 16 h decreased the total
      proportion of TUNEL-positive oocytes. Our results indicate that the attachment of
      cumulus cells to oocytes may have a critical role for oocytes undergoing GVBD and
      that coculture with cumulus cells promotes the ability of oocytes to complete
      maturation. Moreover, coculture with cumulus cells may assist the oocyte to avoid
      undergoing DNA fragmentation.

PMID- 15740701
TI  - Effect of exogenous DMNPE-caged ATP on in vitro-matured bovine oocytes prior to
      parthenogenetic activation, fertilisation and nuclear transfer.
AB  - Adenosine triphosphate (ATP) plays an important role during fertilisation of the
      mammalian oocyte through its ability to alter the frequency and duration of
      calcium oscillations. It has also been shown that higher ATP levels correlate
      with increased developmental competence in bovine and human oocytes. During
      somatic cell nuclear transfer (NT), the incoming nucleus is remodelled
      extensively, undoubtedly using a variety of ATP-dependent enzymes. The aim of the
      present study was to determine whether additional exogenous ATP influences
      activation of parthenogenetic (PA), in vitro-fertilised (IVF) or cloned (NT) in
      vitro-matured bovine oocytes. Blastocyst development and cell numbers in PA
      embryos were found to increase in a dose-dependent manner following the
      photorelease of 0, 50, 100, 500 and 1000 microm DMNPE-caged ATP (adenosine 5'
      triphosphate, P3-(1-(4,5-dimethoxy-2-nitrophenyl)ethyl) ester, disodium salt). No
      cleavage was found following release of 2 and 5 mm DMNPE-caged ATP or with DMNPE
      caged ATP (not photoreleased). There were also no differences in blastocyst rates
      or cell numbers between the control group and groups treated with caged, but not
      photoreleased, ATP. The addition of exogenous ATP before IVF or to NT couplets
      did not result in a significant increase in blastocyst development or cell
      number. Embryo transfer is necessary to determine whether exogenous ATP can
      positively affect reprogramming, resulting in higher cloned pregnancy rates or
      live-term births.

PMID- 15740702
TI  - Embryonic disc development and subsequent viability of cattle embryos following
      culture in two media under two oxygen concentrations.
AB  - Bovine embryos were produced in vitro using a 2 x 2 design of modified medium
      (KSOM or SOF) and oxygen concentration (5% or 20%). Day 7 blastocysts were
      transferred in bulk (n = 11, on average) to recipient heifers and recovered non
      surgically at Day 14. In two replications of a Latin square, eight heifers
      received embryos from each combination of factors. Recovered embryos were
      evaluated for trophoblast length and width, as well as the presence and diameter
      of an embryonic disc (ED). An ED was detected in a higher percentage of embryos
      that had been cultured in KSOM than SOF (72% v. 46%, respectively; P < 0.05). The
      aim of a second series of experiments was to associate Day 14 morphology with
      subsequent developmental capacity. In vitro-produced blastocysts were transferred
      (n = 17-20) on Day 7 to each of eight heifers and recovered at Day 14. Thirty
      eight blastocysts were retransferred to heifers following morphological
      evaluation. Embryos in which an ED with no signs of degeneration had been
      detected maintained more pregnancies than other embryos in which an ED had either
      shown signs of degeneration or had not been detected (5/8 v. 2/30, respectively;
      P < 0.01). Further investigation into ED integrity at the elongating stage may
      contribute to our understanding of pregnancy establishment and maintenance.

PMID- 15740703
TI  - Effects of repetition, interval between treatments and season on the results from
      laparoscopic ovum pick-up in goats.
AB  - The present study was conducted to evaluate the follicular response and oocyte
      yield following repeated gonadotrophin stimulation and laparoscopic aspiration in
      goats and to assess the effects of the time interval between procedures and
      season. A total of 98 adult goats were subjected to laparoscopic ovum pick-up
      (LOPU) five consecutive times in a transgenic production programme. Oestrus was
      synchronised by means of intravaginal sponges inserted for 10 days coupled with
      125 microg cloprostenol 36 h before sponge removal and LOPU, and follicular
      development was stimulated with 80 mg follicle stimulating hormone and 300 IU
      equine chorionic gonadotrophin administered 36 h before LOPU. No difference was
      detected in the response for LOPUs 1, 2, 3 and 4. Although a small decrease in
      response was detected at LOPU 5 (P < 0.05), the numbers of follicles aspirated
      and oocytes recovered were not different from those at LOPU 1 and LOPUs 1 and 4,
      respectively. With respect to time interval between LOPU and season, all
      intervals and seasons produced acceptable responses, with no difference in
      follicles aspirated and oocytes recovered between intervals and seasons. These
      results indicate that LOPU may be repeated up to five times in goats at different
      intervals and in different seasons with little or no important change in overall
      response.

PMID- 15740704
TI  - Reproductive performance in female Clock Delta19 mutant mice.
AB  - The relationship between circadian rhythmicity and rodent reproductive cyclicity
      is well established, but the impact of disrupted clock gene function on
      reproduction has not been well established. The present study evaluated the
      reproductive performance of mice carrying the Clock(Delta19) mutation that were
      either melatonin deficient (Clock(Delta19/Delta19)) or had the capacity to
      synthesise melatonin reinstated (Clock(Delta19/Delta19)+MEL). The
      Clock(Delta19/Delta19) mice took 2-3 days longer to mate, and to subsequently
      deliver pups, than their control line. The melatonin-competent mutants had a
      smaller, but still significant (P < 0.05), delay. The Clock(Delta19) mutation
      resulted in smaller median litter sizes compared with control lines (seven v.
      eight pups; P < 0.05), whereas melatonin proficiency reversed this difference.
      Survival to weaning was 84% and 80% for the Clock(Delta19/Delta19) and
      Clock(Delta19/Delta19)+MEL lines, respectively, compared with 94-96% for the two
      control lines. The Clock(Delta19/Delta19) mutants became behaviourally arrhythmic
      in constant darkness but, despite this, seven of seven became pregnant when
      paired with males after at least 14 days of constant darkness (five of seven
      within 4 days of pairing). In the Clock(Delta19/Delta19)+MEL mice, seven of 15
      became arrhythmic in constant darkness but still became pregnant. The seven mice
      that free ran for at least 14 days in constant darkness with a period of 27.1 h
      also became pregnant. The present study has demonstrated that the Clock(Delta19)
      mutation has significant, but subtle, effects on reproductive performance. The
      reintroduction of melatonin competency and/or other genes as a result of crosses
      with CBA mice reduced the impact of the mutation further. It would appear that
      redundancy in genes in the circadian system allows the reproductive cyclicity to
      persist in mice, albeit at a suboptimal level.

PMID- 15740705
TI  - Sperm transport, size of the seminal plug and the timing of ovulation after
      natural mating in the female tammar wallaby Macropus eugenii.
AB  - The distribution of spermatozoa and seminal plug in the reproductive tract and
      the timing of ovulation were examined at various times in a naturally mated
      monovular macropodid marsupial, namely the tammar wallaby (Macropus eugenii).
      After the first post partum (p.p.) mating, 28 females were isolated and their
      reproductive tracts dissected at 0.5, 6, 18, 36 and 40 h post coitum (p.c.). Each
      tract was ligated into 13 major anatomical sections and spermatozoa and eggs were
      recovered by flushing. Mating was possibly delayed by handling and occurred 21.7
      +/- 2.5 h p.p. in these animals. Copulation lasted 7.8 +/- 0.7 min. Within 0.5 h
      after a single mating, the tract contained 25.8 +/- 10.2 x 10(6) spermatozoa and
      21.6 +/- 8.8 g of seminal plug, 96% and 70% of which was lost within 6 h p.c.
      respectively. Spermatozoa reached the uterus, isthmus and ampulla of the oviduct
      on the side of the developing follicle within 0.5, 6 and 18 h p.c., respectively,
      and a uterine population of 26.1 +/- 12.10(3) spermatozoa was maintained for over
      40 h. Sperm numbers were reduced at the cervix (up to 57-fold) and uterotubule
      junction (eight-fold) and only one in approximately 7500 ejaculated spermatozoa
      (3.4 +/- 0.9 x 10(3)) reached the oviduct on the follicle side. Differential
      transport of spermatozoa was not observed. Although the numbers of spermatozoa
      were reduced in the parturient uterus, they were highly variable and were not
      significantly different to those in the non-parturient uterus. Ovulation and
      recovery of sperm-covered eggs from the isthmus occurred 36-41 h p.c. (49-72 h
      p.p.). In contrast with the polyovular dasyurid and didelphid marsupials, the
      tammar wallaby ejaculates large numbers of spermatozoa, but transport is
      relatively inefficient and sperm storage in the tract before ovulation is
      limited.

PMID- 15740706
TI  - Dynamics of the responses in secretion of luteinising hormone, leptin and insulin
      following an acute increase in nutrition in mature male sheep.
AB  - In Merino rams, an increase in the plane of nutrition increases the frequency of
      luteinising hormone (LH) pulses within a few days and this response is correlated
      with changes in the circulating concentrations of metabolic hormones. To analyse
      early dynamic aspects of these responses, we studied mature rams fed with diets
      that contained either low or high amounts of energy and protein. Jugular blood
      was sampled every 20 min for 96 h, including a control period of 24 h before the
      change of diet in the high-diet group. In the high-diet group, a significant
      increase in LH pulse frequency was first detected 6 h after the increase in
      nutrition on Day 1 and the frequency remained significantly elevated throughout
      the 72-h treatment period, except for a 12-h period on Day 2. Following the
      change of diet, insulin concentrations increased within 3 h and leptin
      concentrations increased within 7 h, after which time the concentrations of both
      hormones remained high. Dietary treatment did not affect the concentrations of
      thyroxine or insulin-like growth factor-I, but the high diet increased the
      concentrations of tri-iodothyronine. These observations are consistent with
      insulin and leptin playing a role in the early activation of the gonadotrophin
      releasing hormone-LH axis by nutritional inputs.

PMID- 15740707
TI  - Minor gland saliva flow rate and proteins in subjects with hyposalivation due to
      Sjogren's syndrome and radiation therapy.
AB  - In this study, the secretion rate and IgA, albumin and lactoferrin concentrations
      in minor labial and buccal gland saliva were investigated in individuals with
      hyposalivation due to primary Sjogren's syndrome (pSS; 10 subjects) or head and
      neck radiation therapy (RT; 10 subjects) and in their matched controls. Whole
      saliva was similarly examined. The minor gland saliva flow was measured using the
      Periotron method. IgA, albumin and lactoferrin concentrations were analysed by
      ELISA techniques. A general finding was that the flow rate and protein
      concentrations were lower in labial than in buccal gland saliva. In both
      hyposalivation groups, the labial minor gland saliva secretion rate was lowered
      compared to their respective controls. The buccal gland saliva flow rate was
      significantly reduced in the RT group only. IgA and albumin concentrations were
      not different from the controls in the labial secretions. The concentration of
      lactoferrin was increased in the RT group. In buccal saliva, the concentrations
      of all proteins examined but pSS IgA, were increased compared to the controls.
      Reduced flow rate and increased protein concentrations were seen for whole saliva
      where the lactoferrin concentration was higher in RT than in pSS subjects. Thus,
      our findings suggested that minor gland saliva flow rate and protein
      concentrations are affected in RT and pSS subjects and to highest extent in the
      former.

PMID- 15740709
TI  - Estimation of fluoride distribution in the mandible and teeth of the red deer
      (Cervus elaphus L.) from industrially polluted areas in Poland.
AB  - MINI SUMMARY: Animals from areas contaminated by industrial emissions containing
      fluoride may accumulate it predominantly in hard tissues. Therefore, an analysis
      was performed for the determination of fluoride content in mandibles and teeth of
      deer living at large in different areas in Western Pomerania (Poland). Samples of
      hard tissues obtained with a dental drill, were dissolved in perchloric acid and
      analyzed for fluoride content with an ion-selective electrode. Using the
      Generalized Regression Neural Network (GRNN), it was possible to arrange definite
      variables according to their order of importance concerning the fluoride mean
      content in investigated bone material. Parametric analysis revealed in which
      sites of mandibles and teeth the fluoride accumulation was the highest. In our
      calculation, the traditional statistic as well as artificial neural network was
      applied. OBJECTIVE: One of the interesting properties of fluoride is its
      balancing accumulation in the hard and soft tissues. In this paper, we decided
      estimate how the changeable doses of fluoride in natural environment influence on
      fluoride distribution and accumulation in the examined sites of mandible and
      teeth. MATERIAL AND METHOD: The material consist of 103 mandibles of red deer
      (Cervus elaphus L.) from five forestry districts of Western Pomerania in Poland,
      which are located near or far away from two major industrial plants: Police
      Chemical Work and the Dolna Odra Coal Power Plant. Samples (10 mg of powdered
      bone or tooth) were dissolved in perchloric acid and the fluoride content was
      determined with an ion-selective electrode. Comparisons were done with the
      Statistica 5.5 and Statistica Neural Networks. RESULTS: Animals living in Western
      Pomerania (Poland) have high fluoride contents in their bones. Fluoride
      accumulation in mandibles and teeth is irregular. The higher content of fluoride
      show incisal area, but coronoid process of the mandible was not sensitive to
      different exposure of environmental fluoride at all. Parametric analysis revealed
      that the accumulation pattern of fluorine was different in the two groups of
      deer. CONCLUSIONS: Many biological and environmental factors may influence on
      incessant fluoride accumulation in osseous tissue of ruminants living at large.
      The use of artificial neural networks enables a more accurate insight into the
      process of fluorine accumulation in the mandible and teeth and helps in the
      ranking of factors influencing this process.

PMID- 15740708
TI  - Transglutaminase 2 expression in the salivary myoepithelial cells of mouse
      embryo.
AB  - Earlier a strong transient expression of transglutaminase 2 (TGase 2) localized
      at the anchoring sites of muscle bundles in human embryo was observed. In this
      study, we report a similar transient expression of the TGase 2 in the salivary
      myoepithelial cells of mouse embryo by immunohistochemistry, RNA in situ
      hybridisation, and RT-PCR. From 35 submandibular glands of mouse embryos and
      postnatal mice, a consistent expression of TGase 2 in the myoepithelial cells via
      a stage-specific manner was identified by mono-clonal antibody to TGase 2
      immunostaining. A similar expression pattern of TGase 2 in the myoepithelial
      cells was also observed by RNA in situ hybridisation analysis. The expression of
      TGase 2 in the salivary epithelium and mesenchyme during the prenatal 14.5-15.5
      days was found minimally diffusely spread and became intensely focalised in the
      myoepithelial cells of salivary acini and ducts during the prenatal 16.5-18.5
      days but thereafter gradually decreased until postnatal 7 days and remained weak
      in postnatal 3 weeks. Such transient rise and fall expressions of TGase 2 were
      also found with the sequential amount of RT-PCR products during the same period.
      The alpha-smooth muscle actin (alpha-SMA) as a positive control in the
      myoepithelial cells of mouse submandibular glands was consistently expressed
      during the prenatal and postnatal period. These results of transient expression
      of TGase 2 in the myoepithelial cells coincided with the formation of the
      dendritic basket structure in the periphery of acini and ducts, suggest a
      possible catalytic role of transglutaminase in a newly formed cellular matrixes
      during the cytodifferentiating stage of mouse prenatal and neonatal submandibular
      glands.

PMID- 15740710
TI  - Enamel fluoride uptake of a novel water-based fluoride varnish.
AB  - Aim of the in situ-study was to evaluate fluoride retention in sound and
      demineralised enamel after application of a novel water-based fluoride (0.12% F)
      varnish Mirafluorid (Hager and Werken, Germany) compared to the resin-based
      varnish (2.26% F) Duraphat (Colgate, USA). Each five enamel specimens were
      prepared from 60 bovine incisors. In 150 of these specimens, incipient lesions
      were produced with acidic hydroxyethylcellulose (pH 4.8; 72 h), 150 specimens
      were not demineralised. The samples were equally (n=100) allotted to three groups
      (A: Mirafluord, B: Duraphat, and C: control). Each 80 specimens (40 demineralised
      and 40 sound) were varnished with either Mirafluorid or Duraphat or remained
      unfluoridated (controls). The other specimens were used for measuring base-line
      fluoride content of the respective tooth. Each six specimens (three demineralised
      and three sound) were fixed in intraoral appliances worn for 5 days by 10
      volunteers in three series (A-C). During the experiment, the samples were brushed
      twice daily with fluoridated toothpaste. KOH-soluble and structurally bound
      fluoride (0-30 and 31-60 microm depth) was determined immediately, 1, 3 and 5
      days after fluoridation. Fluoride uptake was calculated as compared to base-line
      content and statistically analysed. Immediately after fluoridation, uptake of KOH
      soluble and structurally bound fluoride was similar for Mirafluorid and Duraphat
      in both demineralised and sound enamel. However, at day 1, 3 and 5 statistically
      significantly higher amounts of KOH-soluble and structurally bound fluoride were
      found in the samples treated with Duraphat. For Mirafluorid only the uptake for
      KOH-soluble fluoride and structurally bound fluoride in the first enamel layer (0
      30 microm) of the demineralised samples was significantly higher compared to the
      controls (C). It is concluded that the novel fluoride varnish Mirafluorid
      deposits less KOH-soluble and structurally bound fluoride on both demineralised
      and sound enamel compared to Duraphat under in situ-conditions.

PMID- 15740711
TI  - Effects of diet on the incidence of dental pathology in free living caviomorph
      rodents.
AB  - Examinations of dental pathology in five genera of caviomorph rodents found
      caries and periodontal disease in both grazers and frugivores, although the
      prevalence differed between the two groups. Caries was more prevalent in the
      frugivores (10.5-19.8%) than in the grazers (1.1-8.7%); mild periodontal disease
      occurred occasionally in the grazers (5.6-8.7%), but was almost absent in the
      frugivores (0.0-1.3%). The consistent findings of caries and periodontal disease
      suggest that ecological differences between the two related groups, and the
      subsequent dietary differences, are important in determining the incidence of
      dental pathology.

PMID- 15740712
TI  - Behavioural responses following tooth injury in rats.
AB  - Early changes in spontaneous behaviour (exploration, grooming, freezing, rearing,
      jaw motion, yawning) and body weight were measured at two and three days after
      pulp exposure injury and implantation of Fluorogold (FG) into molar teeth of
      rats. Rats with FG and injuries to three teeth gained weight less rapidly,
      explored less frequently and froze more often than sham-operated rats. Yawning
      was not observed in any rats prior to surgery and it was seen more frequently in
      tooth-injured rats than in sham-operated rats. These results suggest that careful
      observation of spontaneous behaviour after tooth injuries can be used to assess
      dental pain in rats and may provide behavioural markers to correlate with
      anatomical changes after injury. The dental nerve cell bodies that had
      accumulated transported FG were medium to large, and they only co-localized
      calcitonin gene-related peptide (CGRP) in a subset of the medium neurons.
      Chromatolytic or moribund FG-labelled neurons were also found.

PMID- 15740713
TI  - Influence of sample type and collection method on Streptococcus mutans and
      Lactobacillus spp. counts in the oral cavity.
AB  - OBJECTIVES: This study compared three methods of Streptococcus mutans and
      Lactobacillus spp. detection in the oral cavity: saliva swab (SS)-sample of
      stimulated saliva collected with swab; whole saliva (WS)-sample of 2 ml of
      stimulated saliva; and the dental plaque method (DP)-plaque sample of all dental
      surfaces. METHODS: Thirty children were included in this study. In the first 15
      children, the SS and WS methods were carried out before the dental plaque
      collection, and in the following 15, the sequence was inverted to evaluate
      possible interference of the methods sequence. The samples were diluted and
      inoculated in SB20 and Rogosa agar, respectively for S.mutans and Lactobacillus
      spp., at 37 degrees C for 48 h. RESULTS: The results (cfu/mL) of S. mutans were
      analysed by the statistical Friedman's test. The levels of Lactobacillus spp.
      were analysed by descriptive statistics due to the high proportion of zero counts
      in the culture. In the first sequence of methods, the number of S. mutans counted
      for the SS method was inferior to DP and WS (P<0.05), and the results for the WS
      and DP methods were similar. The detection of Lactobacillus spp. was observed
      just by the WS (100%) and SS (14.3%) methods. However, in the second experimental
      set the number of S. mutans detected by the DP method was similar to those of the
      SS and WS, however, the WS method showed higher values than SS (P<0.05). A
      greater number of Lactobacillus spp. was detected by the WS method (100%),
      followed by SS (55.5%) and DP (33.3%). CONCLUSIONS: The dental plaque collection
      and the sample of stimulated whole saliva presented similar results in the S.
      mutans count. The most suitable method to detect the Lactobacillus spp. level in
      the oral cavity is the stimulated whole saliva method.

PMID- 15740714
TI  - Mutans streptococci in preschool twins.
AB  - OBJECTIVE: The purpose of this study was to determine whether genetic factors
      influence variation in salivary levels of the mutans streptococci (MS) in
      preschool twins. DESIGN: The study population consisted of 48 pairs of
      monozygotic (MZ) twins and 54 pairs of dizygotic (DZ) twins. Genotyping eight
      highly polymorphic DNA markers determined zygosity. Demographic data and
      antibiotic exposure as reported by mothers were obtained by a face-to-face
      interview. Salivary levels of MS were determined by the Stripmutanstrade mark
      test. Test results are reported on a scale of 0-3. Regression analysis, two
      sample t-tests and structural equation modeling were applied to analyse the data.
      RESULTS: Only 6% of the participants ever visited a dentist (F component of the
      DMFS was 0 for this population). Average salivary scores for the mutans
      streptococci were significantly different between MZ (1.1+/-0.1) and DZ (0.8+/
      0.1) twins (p=0.021). High salivary levels of MS (scores 2 and 3) were observed
      in 42% of MZ twins and in 26% of DZ twins. Regression analysis on the MS salivary
      levels revealed no significant effects of age, gender and antibiotic intake for
      MZ or DZ twins. The heritability of mutans streptococci colonisation in 48 pairs
      MZ and in 26 pairs of DZ twins was estimated to be 52%. The non-shared
      environment contribution was estimated to be 48%. CONCLUSIONS: These results
      suggest that variation in the salivary levels of the mutans streptococci is
      significantly contributed by genetic factors.

PMID- 15740715
TI  - Use of hand held photopolymerizer to photoinactivate Streptococcus mutans.
AB  - OBJECTIVES: The main focus of this research was to investigate the photodynamic
      therapy (PDT), in vitro, acting on Streptococcus mutans and fibroblasts. A hand
      held photopolymerizer (HHP) and a classical photosensitizer (Rose Bengal) were
      used to induce photodynamic response. METHODS: S. mutans and fibroblast were
      treated with different concentrations of Rose Bengal (0-50 microM) irradiated
      with light (400-500 nm) for different time periods (0-40s) and then cell
      viability was evaluated. RESULTS: It was observed that the light (per se) is not
      toxic and in the dark Rose Bengal is toxic to the cells tested only at
      concentrations above 2.5 microM. Under light exposure concentrations of Rose
      Bengal above 0.5 microM all S. mutans were killed with no cytotoxic effects to
      fibroblasts. CONCLUSIONS: For the purpose of this work, the photoactivation of
      Rose Bengal, using the HHP, inactivated the bacteria without affecting the
      fibroblast viability.

PMID- 15740716
TI  - Assessment of bony resection margins in oral cancer using elastic scattering
      spectroscopy: a study on archival material.
AB  - Oral squamous cell carcinoma has been shown to infiltrate local bone
      necessitating either a local or segmental resection for clearance. The current
      decalcification process takes several weeks before histological examination of
      the margins is possible. The aim of this study was to determine whether elastic
      scattering spectroscopy (ESS) could be used to identify bone resection margins
      positive for tumour. We used an ESS biopsy (optical biopsy) system to assess
      formalin fixed bone margins resected for squamous cell carcinoma of the oral
      cavity and compared the results with the histopathological diagnosis. Archival
      specimens obtained in oral cancer resections over the last 10 years were used,
      the ESS spectra were obtained from residual resection margins immediately
      adjacent to the area from which sections were cut and the results correlated with
      the histopathological diagnosis. Three hundred and forty-one spectra were used in
      this study taken from the mandibular specimens of 21 patients, of which 231
      spectra were taken from histologically positive sites and the rest were of normal
      tissue. Two different sets of spectra were obtained and using a linear
      discriminant analysis, a sensitivity of 87% and a specificity of 80% were
      obtained. These results suggest that ESS may identify tumour involvement of
      resection margins. This study, on formalin fixed tissue, was shown to be reliable
      and may significantly reduce pathology workload. If these findings can be applied
      in vivo, this would be an accurate and instant mechanism for assessment of
      margins in clinical practice.

PMID- 15740717
TI  - Effect of tensile force on the expression of IGF-I and IGF-I receptor in the
      organ-cultured rat cranial suture.
AB  - Insulin-like growth factors (IGFs) play an important role in the regulation of
      bone metabolism. In this study, we investigated changes in the expression of IGF
      I and IGF-I receptor and cell proliferation when a continuous tensile force was
      applied to the cranial suture of cultured rat calvaria. The parietal bones with
      the midsagittal suture were removed from male Wistar rats (19-days old), cultured
      for 24h, and divided into two groups. In the experimental group, tensile force (3
      x 10(-3)N) was applied by helical springs to the midsagittal suture, whereas
      helical springs with no tension (0 N) were set in the control group. The tensile
      force significantly increased the expression of both IGF-I mRNA and protein (P <
      0.05). By using in situ hybridisation, we also confirmed that IGF-I and IGF-I
      receptor mRNAs were localized in osteoblast-like and fibroblastic cells subjected
      to the tensile force. Also, this force stimulated the proliferation of osteoblast
      like and fibroblastic cells in calvaria, without affecting their alkaline
      phosphatase activity. These results indicate that a tensile force applied to a
      cranial suture can cause an increase in the production of IGF-I and IGF-I
      receptors in osteoblast-like and fibroblastic cells, and this increase in IGF-I
      may cause the proliferation of the cells in an autocrine or paracrine manner.

PMID- 15740718
TI  - A "locked-on," constitutively active mutant of the adenosine A1 receptor.
AB  - We studied the wild-type human adenosine A1 receptor and three mutant receptors,
      in which the glycine at position 14 had been changed into an alanine, a leucine,
      or a threonine residue. All receptors were characterized in radioligand binding
      experiments, the wild-type and the Gly14Thr mutant receptor in greater detail.
      Both receptors were allosterically modulated by sodium ions and PD81,723 (2-amino
      4,5-dimethyl-3-thienyl-[3(trifluoromethyl)-phenyl]methanone), although in a
      different way. All mutant receptors appeared to be spontaneously or
      "constitutively" active in a [35S]GTPgammaS binding assay, the first
      demonstration of the existence of such CAM (constitutively active mutant)
      receptors for the adenosine A1 receptor. The Gly14Thr mutant receptor was also
      constitutively active in another functional assay, i.e., the inhibition of
      forskolin-induced cAMP production in intact cells. Importantly, this mutant
      displayed a peculiar "locked-on" phenotype, i.e., neither agonist nor inverse
      agonist was capable of modulating the basal activity in both the GTPgammaS and
      the cAMP assay, unlike the wild-type and the two other mutant receptors.

PMID- 15740719
TI  - Binding domains of the oxytocin receptor for the selective oxytocin receptor
      antagonist barusiban in comparison to the agonists oxytocin and carbetocin.
AB  - We have analyzed binding domains of the oxytocin receptor for barusiban, a highly
      selective oxytocin receptor antagonist, in comparison to the combined vasopressin
      V1A/oxytocin receptor antagonist atosiban and the agonists oxytocin and
      carbetocin. For this purpose, chimeric 'gain-in function' oxytocin/vasopressin V2
      receptors were expressed in COS-7 cells. These recombinant receptors have been
      produced by transfer of domains from the oxytocin receptor into the related
      vasopressin V2 receptor and have already been successfully employed for the
      identification of ligand binding domains at the oxytocin receptor (Postina, R.,
      Kojro, E., Fahrenholz, F., 1996. Separate agonist and peptide antagonist binding
      sites of the oxytocin receptor defined by their transfer into the V2 vasopressin
      receptor. J. Biol. Chem. 271, 31593-31601). In displacement studies with 10
      chimeric receptor constructs, the binding profile of barusiban was compared with
      the binding profiles of the ligands oxytocin, [Arg8]vasopressin, carbetocin, and
      atosiban. The binding profiles for the agonists oxytocin and carbetocin were
      found to be similar. For both agonists, important binding domains were the
      extracellular N-terminus (=E1) and the extracellular loops E2 and E3 from the
      oxytocin receptor. For the vasopressin V1A/oxytocin receptor antagonist atosiban,
      none of the receptor constructs were able to provide a binding with higher
      affinity than the starting vasopressin V2 receptor. In contrast, the binding of
      barusiban was significantly improved when the transmembrane domains 1 and 2 were
      transferred from the oxytocin receptor to the vasopressin V2 receptor. The
      binding domain of barusiban differs from the binding domain of the agonists and
      the nonselective oxytocin receptor antagonist d(CH2)5[Tyr
      (Me)2,Thr4,Orn8,Tyr9]vasotocin that has been used in previous studies. Overall,
      the data supported the concept of a central pocket site within the oxytocin
      receptor.

PMID- 15740720
TI  - Dehydrocrotonin and its beta-cyclodextrin complex: cytotoxicity in V79
      fibroblasts and rat cultured hepatocytes.
AB  - Trans-dehydrocrotonin has antiulcerogenic and antitumor activities. A complex of
      beta-cyclodextrin with dehydrocrotonin was developed to improve the delivery of
      dehydrocrotonin. Complex in solid state was evaluated using X-ray diffraction
      (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis
      (TGA) and scanning electron microscopy (SEM). X-ray diffraction and scanning
      electron microscopy studies showed that dehydrocrotonin exists in a
      semicrystalline state in the complexed form with beta-cyclodextrin. Differential
      scanning calorimetry studies showed the existence of a complex of dehydrocrotonin
      with beta-cyclodextrin. The thermal gravimetric analysis studies confirmed the
      differential scanning calorimetry results of the complex. Free dehydrocrotonin
      and the dehydrocrotonin/beta-cyclodextrin inclusion complex were assayed in
      freshly isolated rat hepatocytes and in V79 cells. Cytotoxicity was determined
      using nucleic acid content, methylthiazoletetrazolium (MTT) reduction and neutral
      red uptake assays. In all assays, there was a large reduction (3.5-16.1-fold) in
      the cytotoxicity of dehydrocrotonin in hepatocytes when complexed with beta
      cyclodextrin, whereas for V79 cells the decrease in cytotoxicity was 1.7- and
      1.87-fold for MTT reduction and nucleic acid content assays, respectively. The
      lower cytotoxicity of the dehydrocrotonin/beta-cyclodextrin complex compared to
      free dehydrocrotonin in rat hepatocytes and V79 cells suggests that such a
      complex may be useful for the administration of dehydrocrotonin in vivo.

PMID- 15740721
TI  - Effect of melatonin on calyculin A-induced tau hyperphosphorylation.
AB  - We have found in the present study that incubation of neuroblastma N2a with
      calyculin A, an inhibitor of protein phosphatase-2A (PP-2A) and protein
      phosphatase-1 (PP-1), reduces cell viability in a dose-dependent manner, and
      leads to tau hyperphosphorylation at tau-1 (Ser198/199/202) and PHF-1
      (Ser396/404) epitopes. In addition to inhibit PP-2A, calyculin A treatment also
      results in significant activation of glycogen synthase kinase-3 (GSK-3).
      Calyculin A induces oxidative stress manifested by elevated level of
      malondialdehyde and decreased activity of superoxide dismutase. When the cells
      were incubated simultaneously with calyculin A and melatonin (25 microM or 50
      microM), the calyculin A-induced decrease in cell viability, tau
      hyperphosphorylation, PP-2A/GSK-3 imbalance and oxidative stress were attenuated
      accordingly. These results suggest (i) that calyculin A induces tau
      hyperphosphorylation not only by inhibition of PP-2A, but also by activation of
      GSK-3 in N2a cells; (ii) that melatonin efficiently attenuates the calyculin A
      induced damages through not only its antioxidant effect but also its modulation
      to the phosphorylation system.

PMID- 15740722
TI  - Antioxidants inhibit human endothelial cell functions through down-regulation of
      endothelial nitric oxide synthase activity.
AB  - We have recently shown that superoxide and hydrogen peroxide are putative
      inducers of angiogenesis in vivo, possibly through up regulation of inducible
      nitric oxide synthase (NOS) and increased production of endogenous nitric oxide
      (NO). The aim of the present work was to elucidate the implication of reactive
      oxygen species in endothelial cell functions, using cultures of human umbilical
      vein endothelial cells (HUVEC). Superoxide dismutase (SOD), tempol (membrane
      permeable SOD mimetic) and the NADPH oxidase inhibitors, 4-(2-aminoethyl)
      benzenesulfonyl fluoride and apocynin, but not allopurinol, inhibited HUVEC
      proliferation and migration, as well as activity of endothelial NOS (eNOS).
      Catalase and the intracellular hydrogen peroxide scavenger sodium pyruvate
      decreased, while hydrogen peroxide increased HUVEC proliferation, migration and
      activity of eNOS. Dexamethasone induced the proliferation and migration of HUVEC
      and activated eNOS. Nomega-nitro-L-arginine methyl ester (L-NAME), but not Nomega
      nitro-D-arginine methyl ester, decreased endothelial cell functions and reversed
      the effects of dexamethasone and hydrogen peroxide. N5-(1-iminoethyl)-L-ornithine
      dihydrochloride, but not the inducible NOS specific inhibitor N-[[3
      (aminomethyl)phenyl]methyl]-ethanimidamide dihydrochloride also decreased
      endothelial cell functions, similarly to L-NAME. The guanylate cyclase inhibitor
      1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one inhibited HUVEC proliferation in a
      concentration-dependent manner and completely reversed hydrogen peroxide-induced
      proliferation, migration and cGMP accumulation. In conclusion, superoxide and
      hydrogen peroxide seem to play a significant role in promoting endothelial cell
      proliferation and migration, possibly through regulation of eNOS activity.

PMID- 15740723
TI  - Role of GABA(A) receptors in the retrorubral field and ventral pallidum in rat
      jaw movements elicited by dopaminergic stimulation of the nucleus accumbens
      shell.
AB  - The role of gamma-aminobutyric acid (GABA)(A) receptors in the retrorubral field
      in the production of rat repetitive jaw movements was examined, as this nucleus
      receives a GABAergic, inhibitory input from the nucleus accumbens and is
      connected with the parvicellular reticular formation, a region that is directly
      connected with the orofacial motor nuclei. The GABA(A) receptor antagonist
      bicuculline (150 ng/0.2 microl per side) significantly produced repetitive jaw
      movements when injected bilaterally into the retrorubral field, but not the
      ventral pallidum. The effects of bicuculline were GABA(A) receptor specific,
      because the effects were abolished by muscimol, a GABA(A) receptor agonist, given
      into the same site. The bicuculline-induced jaw movements differed qualitatively
      from those elicited by injection of a mixture of (+/-)-6-chloro-7,8-dihydroxy-3
      allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF 82958; 5 microg)
      and quinpirole (10 microg), agonist at dopamine D1 and D2 receptors respectively,
      into the nucleus accumbens shell. Nevertheless, bilateral injections of muscimol
      (10 ng, 25 ng and 50 ng/0.2 microl per side) into the retrorubral field
      significantly inhibited jaw movements evoked by the dopamine D1/D2 receptor
      stimulation in the nucleus accumbens shell. Bilateral injections of bicuculline
      (50 ng and 150 ng/0.2 microl per side) also reduced the dopamine D1/D2 receptor
      mediated jaw movements. Essentially similar effects were obtained when muscimol
      and bicuculline were given into the ventral pallidum, a region that is also known
      to receive GABAergic inhibitory inputs from the nucleus accumbens. In conclusion,
      GABA(A) receptor blockade in the retrorubral field elicits characteristic
      repetitive jaw movements, and the GABA(A) receptors in that region as well as in
      the ventral pallidum modulate the accumbens-specific, dopamine D1/D2 receptor
      mediated jaw movements.

PMID- 15740724
TI  - Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin
      reuptake inhibitor, vilazodone.
AB  - Vilazodone has been reported to be an inhibitor of 5-hydoxytryptamine (5-HT)
      reuptake and a partial agonist at 5-HT1A receptors. Using [35S]GTPgammaS binding
      in rat hippocampal tissue, vilazodone was demonstrated to have an intrinsic
      activity comparable to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT). Vilazodone (1-10 mg/kg p.o.) dose-dependently
      displaced in vivo [3H]DASB (N,N-dimethyl-2-(2-amino-4
      cyanophenylthio)benzylamine) binding from rat cortex and hippocampus, indicating
      that vilazodone occupies 5-HT transporters in vivo. Using in vivo microdialysis,
      vilazodone (10 mg/kg p.o.) was demonstrated to cause a 2-fold increase in
      extracellular 5-HT but no change in noradrenaline or dopamine levels in frontal
      cortex of freely moving rats. In contrast, administration of 8-OH-DPAT (0.3 mg/kg
      s.c.), either alone or in combination with a serotonin specific reuptake
      inhibitor (SSRI; paroxetine, 3 mg/kg p.o.), produced no increase in cortical 5-HT
      whilst increasing noradrenaline and dopamine 2 and 4 fold, respectively. A 2-fold
      increase in extracellular 5-HT levels (but no change in noradrenaline or dopamine
      levels) was observed after combination of the 5-HT(1A) receptor antagonist, N-[2
      [4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(pyridinyl)cyclohexanecarboxamide)
      (WAY-100635; 0.3 mg/kg s.c.) and paroxetine (3 mg/kg p.o.). In summary,
      vilazodone behaved as a high efficacy partial agonist at the rat hippocampal 5
      HT1A receptors in vitro and occupied 5-HT transporters in vivo. In vivo
      vilazodone induced a selective increase in extracellular levels of 5-HT in the
      rat frontal cortex. This profile was similar to that seen with a 5-HT1A receptor
      antagonist plus an SSRI but in contrast to 8-OH-DPAT either alone or in
      combination with paroxetine.

PMID- 15740725
TI  - Task specificity of cross-tolerance between Delta9-tetrahydrocannabinol and
      anandamide analogs in mice.
AB  - Relatively few studies have compared the effects of tetrahydrocannabinols and
      anandamide-like cannabinoids following repeated dosing. Whereas pronounced
      tolerance develops to many of the in vivo pharmacological effects of Delta9
      tetrahydrocannabinol with repeated dosing, tolerance to anandamide-induced
      effects is typically less noted. In the present study, we examined cross
      tolerance between Delta9-tetrahydrocannabinol and anandamide-like compounds
      (anandamide, 2-methylanandamide, and O-1812) in a tetrad of in vivo tests
      sensitive to cannabinoid action, including spontaneous activity, tail flick,
      rectal temperature, and a ring immobility test of catalepsy. Six intraperitoneal
      injections of Delta9-tetrahydrocannabinol 10 mg/kg over a period of 4 days
      resulted in the development of pronounced tolerance to all of its in vivo
      effects. In contrast, task specificity was observed in cross-tolerance to
      anandamide and its analogs: antinociception (all three compounds), suppression of
      spontaneous activity (2-methylanandamide and O-1812), catalepsy (O-1812), and
      hypothermia (none of the compounds). Furthermore, when it occurred, the magnitude
      of cross-tolerance was notably smaller. These results suggest that anandamide
      like cannabinoids may have a unique pharmacology that only partially overlaps
      with that of Delta9-tetrahydrocannabinol and other traditional cannabinoids.
      Although the basis for this unique pharmacology has not as yet been determined,
      it is possible that regional specificity of cannabinoid CB1 receptor
      downregulation and endocannabinoid release induced by repeated dosing with Delta9
      tetrahydrocannabinol may play a role.

PMID- 15740726
TI  - Cannabinoid CB1 receptor is dispensable for memory extinction in an appetitively
      motivated learning task.
AB  - The interaction of the cannabinoid CB1 receptor with its endogenous ligands plays
      an essential role in extinction of aversive memories (Marsicano, G., Wotjak,
      C.T., Azad, S.C., Bisogno, T., Rammes, G., Cascio, M.G., Hermann, H., Tang, J.,
      Hofmann, C., Zieglgansberger, W., Di, M., V, Lutz, B., 2002. The endogenous
      cannabinoid system controls extinction of aversive memories. Nature 418, 530
      534). The present study tested the generality of this observation in respect to
      positively-reinforced memories. To this end, male cannabinoid CB1 receptor
      deficient mice (CB1R-/-) and their wild-type littermate controls (CB1R+/+) were
      trained in an appetitively-motivated operant conditioning task, in which food
      deprived animals received a food reward on nose-poking into an illuminated hole.
      During training, CB1R-/- turned out to be less motivated to participate in the
      task. After further restriction of daily food consumption, however, CB1R-/-
      reached the same level of performance as CB1R+/+ as far as number of correct
      responses and errors of omission are concerned. The accuracy of performance
      served as a measure for the memory of the light-reward association and was stable
      at similarly high levels over a retention period of 9 days without additional
      training (97.6+/-0.5% vs. 97.0+/-0.9% correct responses). During subsequent
      extinction training, the positive reinforcement was omitted. As a consequence,
      both CB1R-/- and CB1R+/+ showed a similar decline in accuracy of performance and
      total number of correct responses, accompanied by an increase in errors of
      omission. These data demonstrate that the cannabinoid CB1 receptor is not
      essential for extinction of the stimulus-response association in an appetitively
      motivated learning task.

PMID- 15740727
TI  - Effect of trazodone on hERG channel current and QT-interval.
AB  - Trazodone has been associated with prolonged QT-interval and increased risk of
      polymorphous ventricular tachycardias clinically and has demonstrated in vitro
      inhibition of hERG (human ether-a-go-go-related gene) channel current. This study
      attempts to put the effects of trazodone into perspective by comparing its hERG
      inhibition to that of three agents known to inhibit I(Kr), and comparing the
      effects of trazodone and cisapride on action potential duration and the QT
      interval in the rabbit Langendorff heart preparation. Trazodone inhibited hERG
      channel current in a concentration-dependent manner with an IC50 of 0.69 microM.
      Like astemizole, terfenadine and cisapride, trazodone inhibits hERG channel
      current at clinically relevant concentrations. Like cisapride, trazodone
      increased both the QT-interval and APD90 in the Langendorff heart preparation in
      a reverse frequency-dependent manner at clinically relevant concentrations. These
      data strongly suggest that trazodone prolongs the QT-interval through inhibition
      of hERG channel current.

PMID- 15740729
TI  - Depletion of Ca2+ from intracellular stores of the rat portal vein stimulates a
      tonic contraction.
AB  - The possibility that Ca2+ store depletion can stimulate contraction of the rat
      portal vein was investigated in functional experiments. Ca2+ stores were depleted
      with phenylephrine or cyclopiazonic acid in the absence of extracellular Ca2+ and
      then washed out for 30 min. Upon re-addition of extracellular Ca2+, a tonic
      contraction was produced, showing the stimulus for contraction was Ca2+ store
      depletion. The contractions were abolished by niflumic acid and nifedipine
      however, indicating they were dependent on depolarization resulting from opening
      of Ca2+-activated Cl- channels and Ca2+ influx through voltage-gated channels.
      Cumulative additions of phenylephrine below 3x10(-6) M did not produce tonic
      contractions but did in high K+ Krebs solution, where levcromakalim had no
      effect. This showed the tonic contractions were initially prevented by K+ channel
      opening. Increased Ca2+ entry through voltage-gated channels may therefore
      stimulate Ca2+-activated Cl- channels. Ca2+ store depletion could stimulate this
      by opening store-operated non-selective cation channels, resulting in
      depolarization.

PMID- 15740728
TI  - Lack of synergistic effect of molsidomine and sildenafil on development of
      pulmonary hypertension in chronic hypoxic rats.
AB  - The present study addressed whether combined treatment with a phosphodiesterase
      type 5 inhibitor, sildenafil, and a nitric oxide donor, molsidomine, prevents
      development of pulmonary hypertension in chronic hypoxic rats. Two weeks of
      hypoxia increased right ventricular systolic pressure, and right ventricular and
      lung weight. Treatment with either sildenafil (10 mg/kg/day) or molsidomine (15
      mg/kg/day) in drinking water reduced right ventricular systolic pressure and
      weight, while lung weight was unchanged. Combining sildenafil and molsidomine did
      not have additional effects compared to molsidomine alone. The number of
      muscularized pulmonary arteries with diameters below 50 microm was increased in
      vehicle and sildenafil-treated, but not in molsidomine-treated hypoxic rats.
      Acetylcholine relaxation was blunted in arteries from vehicle and molsidomine
      treated, but not in sildenafil-treated rats. In conclusion, both sildenafil and
      molsidomine blunts pulmonary hypertension and right ventricular hypertrophy in
      chronic hypoxic rats, but no synergistic effects were observed.

PMID- 15740730
TI  - Influence of urocortin and corticotropin releasing factor on venous tone in
      conscious rats.
AB  - The corticotropin releasing factor (CRF) family includes CRF and urocortin. The
      effects of urocortin and CRF (0.3, 1, 3 and 10 nmol/kg, i.v.) relative to those
      of vehicle (0.9% NaCl) on mean arterial pressure and mean circulatory filling
      pressure (index of venous tone) were examined in conscious, unrestrained rats
      that were either intact (unblocked) or ganglion-blocked by treatment with
      mecamylamine (10 mg/kg, i.v.) followed by noradrenaline (4 microg/kg/min, i.v.)
      to increase vasomotor tone. Both urocortin and CRF dose-dependently decreased
      mean arterial pressure in intact rats and ganglion-blocked rats. The depressor
      action of urocortin was greater than that of CRF at all doses. In intact rats,
      neither compound reduced mean circulatory filling pressure. In ganglion-blocked
      rats, urocortin and the highest dose of CRF decreased mean circulatory filling
      pressure. In conclusion, both urocortin and CRF are vasodepressor agents with
      venodilator action.

PMID- 15740732
TI  - Effect of zelandopam, a dopamine D1-like receptor agonist, in puromycin
      aminonucleoside nephrosis rats.
AB  - The present experiment was designed to investigate the role of peripheral
      dopamine D1-like receptors and to evaluate the prophylactic effect of zelandopam,
      a dopamine D1-like receptor agonist, on puromycin aminonucleoside (PA)-induced
      nephrosis in rats. Rats were divided into six groups (n=10 per group): 0.9%
      saline-injected rats (control); PA-injected rats (PAN); PA-injected rats treated
      with the selective dopamine D1-like receptor agonist zelandopam (30, 100, 300
      mg/kg p.o. twice a day); PA-injected rats treated with prednisolone (1 mg/kg p.o.
      once a day). Nephrosis was induced in rats with a single intravenous injection of
      PA at a dose of 50 mg/kg. The effects of zelandopam and prednisolone in PA
      nephrosis rats were evaluated before injection of PA and at 7 and 14 days after
      injection. PA-induced nephrosis was characterized by an increase in urinary
      protein excretion (proteinuria) and plasma total cholesterol. Zelandopam dose
      dependently attenuated the increase in proteinuria and total cholesterol.
      Prednisolone significantly attenuated the increase in proteinuria and total
      cholesterol and resulted in a significant decrease in body weight. The present
      study demonstrates for the first time that zelandopam, a selective dopamine D1
      like receptor agonist, is effective in blunting the development of PA-induced
      nephrosis, and that the effects of zelandopam are dose dependent.

PMID- 15740731
TI  - A new tactic to treat postprandial hyperlipidemia in diabetic rats with
      gastroparesis by improving gastrointestinal transit.
AB  - Improvement of gastrointestinal transit was thought to be a new tactic to treat
      postprandial hypertriglyceridemia in diabetic individuals with gastroparesis.
      Diabetic gastroparesis, lipid load testing, and the effect of domperidone or
      aqueous extract of rhizomes of Rheum palmatum L. on postprandial
      hypertriglyceridemia were evaluated in alloxan-induced diabetic rats. Alloxan
      diabetic animals had a slow gastrointestinal transit, together with delayed and
      exaggerated postprandial hypertriglyceridemia, after oral administration of olive
      oil, which was significantly improved after oral administration of domperidone or
      R. palmatum L. However, atropine could prevent the effects of R. palmatum L. The
      reduced postprandial hypertriglyceridemia was highly correlated with the
      improvement in gastrointestinal transit. These results suggest that promotion of
      gastrointestinal transit may be useful for the treatment of postprandial
      hypertriglyceridemia in diabetic patients with gastroparesis. R. palmatum L. may
      become a new choice for these patients since it has more potential benefits than
      domperidone.

PMID- 15740733
TI  - Endotoxin from various gram-negative bacteria has differential effects on
      function of hepatic cytochrome P450 and drug transporters.
AB  - The differential effects of endotoxin derived from Klebsiella pneumoniae,
      Pseudomonas aeruginosa and Escherichia coli on hepatic cytochrome P450 (CYP)
      dependent drug-metabolizing enzyme activity and on the expression of hepatic
      CYP3A2, CYP2C11, P-glycoprotein and multidrug resistance-associated protein 2
      (Mrp2) was investigated in rats. Endotoxin from all three different pathogens
      significantly decreased the systemic clearance of antipyrine, reflecting reduced
      hepatic drug-metabolizing enzyme activity 24 h after intravenous injection (0.5
      mg/kg). The degree of the decreased systemic clearance by P. aeruginosa endotoxin
      was smaller than that by both K. pneumoniae and E. coli endotoxin. Western blot
      analysis revealed that the down-regulation of CYP3A2 by K. pneumoniae and E. coli
      endotoxin was greater than that by P. aeruginosa endotoxin. However, the down
      regulation of CYP2C11 by all three different endotoxin was almost the same. Both
      K. pneumoniae and P. aeruginosa endotoxin significantly down-regulated P
      glycoprotein, but did not down-regulate Mrp2. E. coli endotoxin had no effect on
      the expression of either P-glycoprotein or Mrp2, probably due to the low dose
      used. The down-regulation of CYP3A2 by endotoxin was parallel to the decreased
      systemic clearance of antipyrine. These results suggest that endotoxin has a
      differential effect on the hepatic CYP-mediated drug-metabolizing enzyme
      activity, and on the protein levels of hepatic CYP3A2 and P-glycoprotein,
      probably due to bacterial source-differences in the production of some
      proinflammatory mediators. Endotoxin appears to regulate coordinately CYP3A2,
      CYP2C11 and P-glycoprotein, but not Mrp2.

PMID- 15740734
TI  - Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and
      its restoration by Y-27632.
AB  - The possible contribution of Rho/Rho-kinase signalling in oleic acid (100 mg kg
      1, i.v., for 4 h)-induced lung injury was investigated in rats. Furthermore, the
      possible protective effect of the administration of a Rho-kinase inhibitor, (+)
      (R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride
      monohydrate (Y-27632, 0.5-5 mg kg-1, i.v., 15 min before the administration of
      oleic acid), was also examined. Western blot analysis as well as
      histopathological examination revealed that Rho-kinase (ROCK-1 and ROCK-2) was
      upregulated in lungs obtained from oleic acid-administrated rats. In addition,
      the markers of oxidative and nitrosative stress, i.e., malondialdehyde,
      myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate, in serum and lung tissue
      were also increased in the injury group. Treatment of rats with 5 mg kg-1 Y-27632
      reversed the oleic acid-induced lung damage, which was demonstrated by
      histopathological assessment and confirmed in Western blot experiments: ROCK
      blots were more intense in the oleic acid group than in control and Y-27632
      treatment reversed ROCK upregulation. In addition, malondialdehyde,
      myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate were also normalized
      after the administration of Y-27632 (0.5 mg kg-1 and 5 mg kg-1). These findings
      suggest that ROCK-1 and ROCK-2 are involved in oleic acid-induced lung damage in
      rats, and that inhibition of this enzyme by Y-27632 may have a protective effect
      against such damage. Consequently, Rho kinase inhibitors may be potential
      therapeutic agents in the treatment of acute respiratory distress syndrome
      (ARDS).

PMID- 15740735
TI  - Oral administration of a T cell epitope inhibits symptoms and reactions of
      allergic rhinitis in Japanese cedar pollen allergen-sensitized mice.
AB  - Although the concept of a T cell epitope in specific immunoprophylaxis was
      proposed more than a decade ago, it had not been well demonstrated since then
      that a T cell epitope inhibits symptoms and reactions of allergic disease in
      animal models. In this study, we have established a system to evaluate symptoms
      and reactions of allergic rhinitis in mice, and investigated whether oral
      administration of a T cell epitope relieves sensitized mice of allergic rhinitis.
      P2-246-259 (RAEVSYVHVNGAKF) is a BALB/c mouse T-cell epitope of Cry j 2, which is
      a major Japanese cedar (Cryptomeria japonica) pollen allergen. Mice were
      administered orally with 200 microg/animal of P2-246-259 four times within 2
      weeks before sensitization, and sensitized intranasally with Cry j 2 twice. Of
      the cardinal symptoms of allergic rhinitis, we assessed sneezing and airway
      obstruction, but could not estimate rhinorrhea or pruritus. Sneezing frequency
      was significantly increased by challenge with Cry j 2. Concerning allergic
      reactions, vascular permeability of the nasal mucosa in the early phase and
      hyperreactivity to histamine in the late phase were also exacerbated by the
      challenge. These symptoms and reactions of allergic rhinitis were significantly
      inhibited by oral administration of P2-246-259. These results indicate utility of
      mice as models for allergic rhinitis; furthermore, the effects of P2-246-259 on
      allergic rhinitis imply that oral administration of a T cell epitope is a
      promising approach for specific immunoprophylaxis.

PMID- 15740736
TI  - Inhibition of choroidal angiogenesis by calcium dobesilate in normal Wistar and
      diabetic GK rats.
AB  - Calcium dobesilate reduces vascular endothelial growth factor (VEGF) over
      expression in diabetic rat retina, but its effect on intraocular angiogenesis is
      unknown. Therefore, we tested calcium dobesilate for its in vitro and ex vivo
      effects on choroidal explant angiogenesis in spontaneously diabetic Goto-Kakizaki
      (GK) rats. Choroidal explants were cultured in gels of collagen. Budded
      microvessels numbers and VEGF formation were taken as markers of angiogenesis. Ex
      vivo studies were performed in GK rats orally given 100 mg/kg/day calcium
      dobesilate for 10 days. In vitro, calcium dobesilate dose- and time-dependently
      inhibited both microvessel formation and VEGF production, at concentrations
      >or=25 mug/ml (i.e. >or=60 microM), with complete inhibition at 100 microg/ml.
      Oral treatment of diabetic GK rats with calcium dobesilate induced a significant
      reduction of choroidal angiogenesis ex vivo (38.8% after 3 days of culture). In
      conclusion, calcium dobesilate inhibited choroidal explant angiogenesis both in
      vitro and ex vivo. This effect may be due, at least in part, to inhibition of
      VEGF production. Antiangiogenesis by calcium dobesilate can be involved in its
      therapeutic benefit in diabetic retinopathy.

PMID- 15740737
TI  - A survey of left-handed helices in protein structures.
AB  - All naturally occurring amino acids with the exception of glycine contain one or
      more chiral carbon atoms and can therefore occur in two different configurations,
      L (levo, left-handed) and D (dextro, right-handed). Proteins are almost
      exclusively built from L-amino acids. The stereochemical bias of nature is
      further reflected at the secondary structure level where right-handed helices are
      strongly preferred over left-handed helices. The handedness of helices has not
      received much attention in the past and is often overlooked during the analysis,
      description and deposition of experimentally solved protein structures.
      Therefore, an extensive survey of left-handed helices in the Protein Data Bank
      (PDB) was undertaken to analyse their frequency of occurrence, length, amino acid
      composition, conservation and possible structural or functional role. All left
      handed helices (of four or more residues) in a non-redundant subset of the PDB,
      were identified using hydrogen-bonding analysis, comparison of related
      structures, and experimental electron density assessment to filter out likely
      spurious and artefactual hits. This analysis yielded 31 verified left-handed
      helices in a set of 7284 proteins. The phi angles of the residues in the left
      handed helices lie between 30 degrees and 130 degrees and the psi angles lie
      between -50 degrees and 100 degrees . Most of the helices are short (four
      residues) and for 87% of them, it was possible to determine that they are
      important for the stability of the protein, for ligand binding, or as part of the
      active site. This suggests that, even though left-handed helices are rare, when
      they do occur, they are structurally or functionally significant. Four secondary
      structure assignment programs were tested for their ability to identify the
      handedness of the helices. Of these programs, only DSSP correctly assigns the
      handedness.

PMID- 15740738
TI  - Dimeric dUTPases, HisE, and MazG belong to a new superfamily of all-alpha NTP
      pyrophosphohydrolases with potential "house-cleaning" functions.
AB  - Structure-guided analysis of the new dimeric dUTPase family revealed its sequence
      relationship to the phage T4 dCTPase, phosphoribosyl-ATP pyrophosphatase HisE,
      NTP pyrophosphatase MazG, and several uncharacterized protein families, including
      the human protein XTP3TPA (RS21-C6), which is overexpressed in embryonic and
      cancer cells. Comparison with the recently determined structure of a MazG-like
      protein from Sulfolobus solfataricus supported the unification of these enzymes
      in one superfamily of all-alpha NTP pyrophosphatases, suggesting that dimeric
      dUTPases evolved from a tetrameric MazG-like ancestor by gene duplication.
      Analysis of the structure of the Sulfolobus MazG points to 2-hydroxyadenosine
      (isoguanosine) triphosphate, a product of oxidative damage of ATP, as the most
      likely substrate. We predict that uncharacterized members of this superfamily
      perform "house-cleaning" functions by hydrolyzing abnormal NTPs and are
      functionally analogous to the structurally unrelated hydrolases of the Nudix
      superfamily. We outline probable tertiary and quaternary structures of the all
      alpha NTP pyrophosphatase superfamily members.

PMID- 15740739
TI  - Mechanistic studies of the T4 DNA (gp41) replication helicase: functional
      interactions of the C-terminal Tails of the helicase subunits with the T4 (gp59)
      helicase loader protein.
AB  - We compare the activities of the wild-type (gp41WT) and mutant (gp41delta C20)
      forms of the bacteriophage T4 replication helicase. In the gp41delta C20 mutant
      the helicase subunits have been genetically truncated to remove the 20 residue C
      terminal tail peptide domains present in the wild-type enzyme. Here, we examine
      the interactions of these helicase forms with the T4 gp59 helicase loader and the
      gp32 single-stranded DNA binding proteins, both of which are physically and
      functionally coupled with the helicase in the T4 DNA replication complex. We show
      that the wild-type and mutant forms of the helicase do not differ in their
      ability to assemble into dimers and hexamers, nor in their interactions with gp61
      (the T4 primase). However they do differ in their gp59-stimulated unwinding
      activities and in their abilities to translocate along a ssDNA strand that has
      been coated with gp32. We demonstrate that functional coupling between gp59 and
      gp41 involves direct interactions between the C-terminal tail peptides of the
      helicase subunits and the loading protein, and measure the energetics and
      kinetics of these interactions. This work helps to define a gp41-gp59 assembly
      pathway that involves an initial interaction between the C-terminal tails of the
      helicases and the gp59 loader proteins, followed by a conformational change of
      the helicase subunits that exposes new interaction surfaces, which can then be
      trapped by the gp59 protein. Our results suggest that the gp41-gp59 complex is
      then poised to bind ssDNA portions of the replication fork. We suggest that one
      of the important functions of gp59 may be to aid in the exposure of the ssDNA
      binding sites of the helicase subunits, which are otherwise masked and regulated
      by interactions with the helicase carboxy-terminal tail peptides.

PMID- 15740740
TI  - NMR snapshots of a fluctuating protein structure: ubiquitin at 30 bar-3 kbar.
AB  - Conformational fluctuation plays a key role in protein function, but we know
      little about the associated structural changes. Here we present a general method
      for elucidating, at the atomic level, a large-scale shape change of a protein
      molecule in solution undergoing conformational fluctuation. The method utilizes
      the intimate relationship between conformation and partial molar volume and
      determines three-dimensional structures of a protein at different pressures using
      variable pressure NMR technique, whereby NOE distance and torsion angle
      constraints are used to create average coordinates. Ubiquitin (pH 4.6 at 20
      degrees C) was chosen as the first target, for which structures were determined
      at 30 bar and at 3 kbar, giving "NMR snapshots" of a fluctuating protein
      structure at atomic resolution. The result reveals that the helix swings in and
      out by >3 angstroms with a simultaneous reorientation of the C-terminal segment,
      providing an "open" conformer suitable for enzyme recognition. Spin relaxation
      analysis indicates that this fluctuation occurs in the ten microsecond time range
      with activation volumes -4.2(+/-3.2) and 18.5(+/-3.0) ml/mol for the "closed-to
      open" and the "open-to-closed" transitions, respectively.

PMID- 15740741
TI  - Structure of a mannan-specific family 35 carbohydrate-binding module: evidence
      for significant conformational changes upon ligand binding.
AB  - Enzymes that digest plant cell wall polysaccharides generally contain non
      catalytic, carbohydrate-binding modules (CBMs) that function by attaching the
      enzyme to the substrate, potentiating catalytic activity. Here, we present the
      first structure of a family 35 CBM, derived from the Cellvibrio japonicus beta
      1,4-mannanase Man5C. The NMR structure has been determined for both the free
      protein and the protein bound to mannopentaose. The data show that the protein
      displays a typical beta-jelly-roll fold. Ligand binding is not located on the
      concave surface of the protein, as occurs in many CBMs that display the jelly
      roll fold, but is formed by the loops that link the two beta-sheets of the
      protein, similar to family 6 CBMs. In contrast to the majority of CBMs, which are
      generally rigid proteins, CBM35 undergoes significant conformational change upon
      ligand binding. The curvature of the binding site and the narrow binding cleft
      are likely to be the main determinants of binding specificity. The predicted
      solvent exposure of O6 at several subsites provides an explanation for the
      observed accommodation of decorated mannans. Two of the key aromatic residues in
      Man5C-CBM35 that interact with mannopentaose are conserved in mannanase-derived
      CBM35s, which will guide specificity predictions based on the primary sequence of
      proteins in this CBM family.

PMID- 15740742
TI  - Solution structure and dynamics of LuxU from Vibrio harveyi, a phosphotransferase
      protein involved in bacterial quorum sensing.
AB  - The marine bacterium Vibrio harveyi controls its bioluminescence by a process
      known as quorum sensing. In this process, autoinducer molecules are detected by
      membrane-bound sensor kinase/response regulator proteins (LuxN and LuxQ) that
      relay a signal via a series of protein phosphorylation reactions to another
      response regulator protein, LuxO. Phosphorylated LuxO indirectly represses the
      expression of the proteins responsible for bioluminescence. Integral to this
      quorum sensing process is the function of the phosphotransferase protein, LuxU.
      LuxU acts to shuttle the phosphate from the membrane-bound proteins, LuxN and
      LuxQ, to LuxO. LuxU is a 114 amino acid residue monomeric protein. Solution NMR
      was used to determine the three-dimensional structure of LuxU. LuxU contains a
      four-helix bundle topology with the active-site histidine residue (His58) located
      on alpha-helix C and exposed to solution. The active site represents a cluster of
      positively charged residues located on an otherwise hydrophobic protein face. NMR
      spin-relaxation experiments identify a collection of flexible residues localized
      on the same region of LuxU as His58. The studies described here represent the
      first structural characterization of an isolated, monomeric bacterial
      phosphotransferase protein.

PMID- 15740743
TI  - Structure of the adaptor protein p14 reveals a profilin-like fold with distinct
      function.
AB  - The adaptor protein p14 is associated with the cytoplasmic face of late endosomes
      that is involved in cell-surface receptor endocytosis and it also directly
      interacts with MP1, a scaffolding protein that binds the MAP kinase ERK1 and its
      upstream kinase activator MEK1. The interaction of p14 with MP1 recruits the
      latter to late endosomes and the endosomal localization of p14/MP1-MEK1-ERK1
      scaffolding complex is required for signaling via ERK MAP kinase in an efficient
      and specific manner upon receptor stimulation. Here, we report the three
      dimensional solution structure of the adaptor protein p14. The structure reveals
      a profilin-like fold with a central five-stranded beta-sheet sandwiched between
      alpha-helices. Unlike profilin, however, p14 exhibits weak interaction with
      selective phosphoinositides but no affinity towards proline-rich sequences.
      Structural comparison between profilin and p14 reveals the molecular basis for
      the differences in these functions. We further mapped the MP1 binding sites on
      p14 by NMR, and discuss the implications of these important findings on the
      possible function of p14.

PMID- 15740744
TI  - Amyloid formation from HypF-N under conditions in which the protein is initially
      in its native state.
AB  - Aggregation of the N-terminal domain of the Escherichia coli HypF (HypF-N) was
      investigated in mild denaturing conditions, generated by addition of 6-12% (v/v)
      trifluoroethanol (TFE). Atomic force microscopy indicates that under these
      conditions HypF-N converts into the same type of protofibrillar aggregates
      previously shown to be highly toxic to cultured cells. These convert
      subsequently, after some weeks, into well-defined fibrillar structures. The rate
      of protofibril formation, monitored by thioflavin T (ThT) fluorescence, depends
      strongly on the concentration of TFE. Prior to aggregation the protein has far-UV
      circular dichroism (CD) and intrinsic fluorescence spectra identical with those
      observed for the native protein in the absence of co-solvent; the quenching of
      the intrinsic tryptophan fluorescence by acrylamide and the ANS binding
      properties are also identical in the two cases. These findings indicate that HypF
      N is capable of forming amyloid protofibrils and fibrils under conditions in
      which the protein is initially in a predominantly native-like conformation. The
      rate constants for folding and unfolding of HypF-N, determined in 10% TFE using
      the stopped-flow technique, indicate that a partially folded state is in rapid
      equilibrium with the native state and populated to ca 1%. A kinetic analysis
      reveals that aggregation results from molecules accessing such a partially folded
      state. The approach described here shows that it is possible to probe the
      mechanism of aggregation of a specific protein under conditions in which the
      protein is initially native and hence relevant to a physiological environment. In
      addition, the results indicate that toxic protofibrils can be formed from
      globular proteins under conditions that are only marginally destabilising and in
      which the large majority of molecules have the native fold. This conclusion
      emphasises the importance for cells to constantly combat the propensity for even
      the most stable of these proteins to aggregate.

PMID- 15740745
TI  - Probing the interactions between the folding elements early in the folding of
      Escherichia coli dihydrofolate reductase by systematic sequence perturbation
      analysis.
AB  - One of the necessary conditions for a protein to be foldable is the presence of a
      complete set of folding elements (FEs) that are short contiguous peptide segments
      distributed over an amino acid sequence. Previous studies indicated the FE
      assembly model of protein folding, in which the FEs interact with each other and
      coalesce to form an intermediate(s) early in the folding reaction. This suggests
      that a clue to the understanding of the determinants of protein foldability can
      be found by investigating how the FEs interact with each other early in the
      folding and thereby elucidating roles of the FEs in protein folding. To reveal
      the formation process of FE-FE interactions, we studied the early folding events
      of Escherichia coli dihydrofolate reductase (DHFR) utilizing systematic sequence
      perturbation analysis. Here, systematic single amino acid substitutions were
      introduced inside of the FEs (W30X in FE2, V40X in FE3, N59X in FE4, and I155X in
      FE10; X refers to various amino acid residues), and their kinetic refolding
      reactions were measured by stopped-flow circular dichroism and fluorescence. We
      show that the interactions around Trp30 and Ile155 are formed in the burst phase
      intermediate, while those around Val40 and Asn59 are formed in the transition
      state of the subsequent folding phase (tau5-phase) and in much later processes,
      respectively. These and previous results suggest that FE2 and FE10, and also FE1
      and FE7, involved in the loop subdomain of DHFR, interact with each other within
      a millisecond time range, while the stable FE3-FE4 interactions are formed in the
      later processes. This may highlight the important roles of the FEs mainly inside
      of the loop subdomain in formation of the burst phase intermediate having a
      hydrophobic cluster and native-like overall topology and in acquisition of the
      foldability of DHFR.

PMID- 15740746
TI  - Comprehensive analysis of protein folding activation thermodynamics reveals a
      universal behavior violated by kinetically stable proteases.
AB  - Alpha-lytic protease (alpha LP) and Streptomyces griseus protease B (SGPB) are
      two extracellular serine proteases whose folding is absolutely dependent on the
      existence of their companion pro regions. Moreover, the native states of these
      proteins are, at best, marginally stable, with the apparent stability resulting
      from being kinetically trapped in the native state by large barriers to
      unfolding. Here, in an effort to understand the physical properties that
      distinguish kinetically and thermodynamically stable proteins, we study the
      temperature-dependences of the folding and unfolding kinetics of alpha LP and
      SGPB without their pro regions, and compare their behavior to a comprehensive set
      of other proteins. For the folding activation thermodynamics, we find some
      remarkable universal behaviors in the thermodynamically stable proteins that are
      violated dramatically by alpha LP. Despite significant variations in
      deltaC(P,F)++, the maximal folding speed occurs within the narrow biological
      temperature range for all proteins, except for alpha LP, with its maximal folding
      speed shifted lower by 200 K. This implies evolutionary pressures on folding
      speed for typical proteins, but not for alpha LP. In addition, the folding free
      energy barrier in the biological temperature range for most proteins is
      predominantly enthalpic, but purely entropic for alpha LP. The unfolding of alpha
      LP and SGPB is distinguished by three properties: a remarkably large
      deltaC(P,U)++, a very high deltaG(U)++, and a maximum deltaG(u)++ at the optimal
      growth temperature for the organism. While other proteins display each of these
      traits to some approximation, the simultaneous optimization of all three occurs
      only in the kinetically stable proteins, and appears to be required to maximize
      their unfolding cooperativity, by suppressing local unfolding events, and slowing
      the rate of global unfolding. Together, these properties extend the lifetime of
      these enzymes in the highly proteolytic extracellular environment. Attaining such
      functional properties seems possible only through the gross perturbation of the
      folding thermodynamics, which in turn has required the co-evolution of pro
      regions as folding catalysts.

PMID- 15740747
TI  - Folding pathway mediated by an intramolecular chaperone: intrinsically
      unstructured propeptide modulates stochastic activation of subtilisin.
AB  - Several secreted proteases are synthesized with N-terminal propeptides that
      function as intramolecular chaperones (IMCs) and direct the folding of proteases
      to their native functional states. Using subtilisin E as our model system, we had
      earlier established that (i) release and degradation of the IMC from its complex
      with the protease upon completion of folding is the rate-determining step to
      protease maturation and, (ii) IMC of SbtE is an extremely charged, intrinsically
      unstructured polypeptide that adopts an alpha-beta structure only in the presence
      of the protease. Here, we explore the mechanism of IMC release and the intricate
      relationship between IMC structure and protease activation. We establish that the
      release of the first IMC from its protease domain is a non-deterministic event
      that subsequently triggers an activation cascade through trans-proteolysis. By in
      silico simulation of the protease maturation pathway through application of
      stochastic algorithms, we further analyze the sub-stages of the release step. Our
      work shows that modulating the structure of the IMC domain through external
      solvent conditions can vary both the time and randomness of protease activation.
      This behavior of the protease can be correlated to varying the release-rebinding
      equilibrium of IMC, through simulation. Thus, a delicate balance underlies IMC
      structure, release, and protease activation. Proteases are ubiquitous enzymes
      crucial for fundamental cellular processes and require deterministic activation
      mechanisms. Our work on SbtE establishes that through selection of an
      intrinsically unstructured IMC domain, nature appears to have selected for a
      viable deterministic handle that controls a fundamentally random event. While
      this outlines an important mechanism for regulation of protease activation, it
      also provides a unique approach to maintain industrially viable subtilisins in
      extremely stable states that can be activated at will.

PMID- 15740748
TI  - In vitro evolutionary thermostabilization of congerin II: a limited reproduction
      of natural protein evolution by artificial selection pressure.
AB  - The thermostability of the conger eel galectin, congerin II, was improved by in
      vitro evolutionary protein engineering. Two rounds of random PCR mutagenesis and
      selection experiments increased the congerin II thermostability to a level
      comparative to its naturally thermostable isoform, congerin I. The crystal
      structures of the most thermostable double mutant, Y16S/T88I, and the related
      single mutants, Y16S and T88I, were determined at 2.0 angstroms, 1.8 angstroms,
      and 1.6 angstroms resolution, respectively. The exclusion of two interior water
      molecules by the Thr88Ile mutation, and the relief of adjacent conformational
      stress by the Tyr16Ser mutation were the major contributions to the
      thermostability. These features in the congerin II mutants are similar to those
      observed in congerin I. The natural evolution of congerin genes, with the
      K(A)/K(S) ratio of 2.6, was accelerated under natural selection pressures. The
      thermostabilizing selection pressure artificially applied to congerin II mimicked
      the implied natural pressure on congerin I. The results showed that the
      artificial pressure made congerin II partially reproduce the natural evolution of
      congerin I.

PMID- 15740749
TI  - Inclining the purine base binding plane in protein kinase CK2 by exchanging the
      flanking side-chains generates a preference for ATP as a cosubstrate.
AB  - Protein kinase CK2 (casein kinase 2) is a highly conserved and ubiquitously found
      eukaryotic serine/threonine kinase that plays a role in various cellular key
      processes like proliferation, apoptosis and circadian rhythm. One of its
      prominent biochemical properties is its ability to use GTP as well as ATP as a
      cosubstrate (dual-cosubstrate specificity). This feature is exceptional among
      eukaryotic protein kinases, and its biological significance is unknown. We
      describe here a mutant of the catalytic subunit of protein kinase CK2 (CK2alpha)
      from Homo sapiens (hsCK2alpha) with a clear and CK2-atypical preference for ATP
      compared to GTP. This mutant was designed on the basis of several structures of
      CK2alpha from Zea mays (zmCK2alpha) in complex with various ATP-competitive
      ligands. A structural overlay revealed the existence of a "purine base binding
      plane" harbouring the planar moiety of the respective ligand like the purine base
      of ATP and GTP. This purine base binding plane is sandwiched between the side
      chains of Ile66 (Val66 in hsCK2alpha) and Met163, and it adopts a significantly
      different orientation than in prominent homologues like cAMP-dependent protein
      kinase (CAPK). By exchanging these two flanking amino acids (Val66Ala, Met163Leu)
      in hsCK2alpha(1-335), a C-terminally truncated variant of hsCK2alpha, the
      cosubstrate specificity shifted in the expected direction so that the mutant
      strongly favours ATP. A structure determination of the mutant in complex with an
      ATP-analogue confirmed the predicted change of the purine base binding plane
      orientation. An unexpected but in retrospect plausible consequence of the
      mutagenesis was, that the helix alpha D region, which is in the direct
      neighbourhood of the ATP-binding site, has adopted a conformation that is more
      similar to CAPK and less favourable for binding of GTP. These findings
      demonstrate that CK2alpha possesses sophisticated structural adaptations in
      favour of dual-cosubstrate specificity, suggesting that this property could be of
      biological significance.

PMID- 15740750
TI  - A ligand-centric analysis of the diversity and evolution of protein-ligand
      relationships in E.coli.
AB  - As enzymes evolve and diverge from common ancestor sequences, they often keep
      their overall reaction chemistry but specialize in the binding of different
      cognate ligands. This study borrows methods for the computational assessment of
      2D similarity of small molecules from the field of chemoinformatics, to examine
      the extent of structure conservation of cognate ligands binding to similar
      proteins. Proteins from 87 structural superfamilies from Escherichia coli form
      the core dataset, which is extended using homologues with functional assignments
      from any organism. We find that correlation of the substrate similarity with
      protein similarity (measured by either sequence-based or structure-based scores)
      can only be clearly established for very similar proteins. At low sequence
      identities, the superfamily to which a protein belongs can give helpful clues to
      its function, and more importantly, the confidence attached to such clues is
      superfamily-dependent. Our data indicate that only a few superfamilies show great
      substrate diversity, and that most exhibit conservation of at least part of the
      structural scaffold of the substrate.

PMID- 15740751
TI  - Nucleotide dependent motion and mechanism of action of p97/VCP.
AB  - The AAA (ATPases associated with a variety of cellular activities) family of
      proteins bind, hydrolyze, and release ATP to effect conformational changes,
      assembly, or disassembly upon their binding partners and substrate molecules. One
      of the members of this family, the hexameric p97/valosin-containing protein
      p97/VCP, is essential for the dislocation of misfolded membrane proteins from the
      endoplasmic reticulum. Here, we observe large motions and dynamic changes of
      p97/VCP as it proceeds through the ATP hydrolysis cycle. The analysis is based on
      crystal structures of four representative ATP hydrolysis states: APO, AMP-PNP,
      hydrolysis transition state ADP x AlF3, and ADP bound. Two of the structures
      presented herein, ADP and AMP-PNP bound, are new structures, and the ADP x AlF3
      structure was re-refined to higher resolution. The largest motions occur at two
      stages during the hydrolysis cycle: after, but not upon, nucleotide binding and
      then following nucleotide release. The motions occur primarily in the D2 domain,
      the D1 alpha-helical domain, and the N-terminal domain, relative to the
      relatively stationary and invariant D1alpha/beta domain. In addition to the
      motions, we observed a transition from a rigid state to a flexible state upon
      loss of the gamma-phosphate group, and a further increase in flexibility within
      the D2 domains upon nucleotide release. The domains within each protomer of the
      hexameric p97/VCP deviate from strict 6-fold symmetry, with the more flexible ADP
      state exhibiting greater asymmetry compared to the relatively rigid ADP x AlF3
      state, suggesting a mechanism of action in which hydrolysis and conformational
      changes move about the hexamer in a processive fashion.

PMID- 15740752
TI  - Mutations in subunits of the Escherichia coli twin-arginine translocase block
      function via differing effects on translocation activity or tat complex
      structure.
AB  - We have used a combination of blue-native (BN) gel electrophoresis and protein
      purification to analyze the effects of TatA or TatC mutations on the structures
      of the primary TatABC and multimeric TatA complexes in Escherichia coli.
      Expression of wild-type TatABC leads to the production of a single major TatABC
      complex of 370 kDa and a heterogeneous set of TatA complexes of <100 kDa to
      approximately 500 kDa. Two TatC mutations that block translocation have different
      effects on complex structures. P48A causes massive defects in TatABC assembly,
      including a marked separation of the TatBC subunits and the production of TatB
      and TatC aggregates. In contrast, TatABC complexes from the inactive TatC F94A
      mutant are structurally intact, suggesting that this mutation affects
      translocation activity rather than assembly. Neither TatC mutation affects the
      separate TatA complexes, showing that assembly of the TatA complexes is
      independent of TatABC assembly or activity. In contrast, three TatA mutations
      affect both the TatA and TatABC complexes. F39A assembles into smaller,
      incorrectly organized TatA complexes and the TatABC complexes contain an
      incorrect TatB:TatC ratio and unusually large amounts of TatA. A triple mutant in
      the amphipathic region forms slightly larger TatA complexes that are likewise
      disorganized, and a mutant containing three glycine substitutions in the
      transmembrane (TM) span assembles as grossly affected TatA complexes that are
      much larger than wild-type complexes. These mutants lead to a partial failure of
      TatB to assemble correctly. The data show that the amphipathic and TM regions
      play critical roles in TatA complex assembly. All of the TatA mutations lead to
      partial or substantial defects in TatABC complex formation, demonstrating that
      the properties of TatA can have a marked influence on the TatABC complex.

PMID- 15740753
TI  - Solution structures of the core light-harvesting alpha and beta polypeptides from
      Rhodospirillum rubrum: implications for the pigment-protein and protein-protein
      interactions.
AB  - We have determined the solution structures of the core light-harvesting (LH1)
      alpha and beta-polypeptides from wild-type purple photosynthetic bacterium
      Rhodospirillum rubrum using multidimensional NMR spectroscopy. The two
      polypeptides form stable alpha helices in organic solution. The structure of
      alpha-polypeptide consists of a long helix of 32 amino acid residues over the
      central transmembrane domain and a short helical segment at the N terminus that
      is followed by a three-residue loop. Pigment-coordinating histidine residue
      (His29) in the alpha-polypeptide is located near the middle of the central helix.
      The structure of beta-polypeptide shows a single helix of 32 amino acid residues
      in the membrane-spanning region with the pigment-coordinating histidine residue
      (His38) at a position close to the C-terminal end of the helix. Strong hydrogen
      bonds have been identified for the backbone amide protons over the central
      helical regions, indicating a rigid property of the two polypeptides. The overall
      structures of the R.rubrum LH1 alpha and beta-polypeptides are different from
      those previously reported for the LH1 beta-polypeptide of Rhodobacter
      sphaeroides, but are very similar to the structures of the corresponding LH2
      alpha and beta-polypeptides determined by X-ray crystallography. A model
      constructed for the structural subunit (B820) of LH1 complex using the solution
      structures reveals several important features on the interactions between the LH1
      alpha and beta-polypeptides. The significance of the N-terminal regions of the
      two polypeptides for stabilizing both B820 and LH1 complexes, as clarified by
      many experiments, may be attributed to the interactions between the short N
      terminal helix (Trp2-Gln6) of alpha-polypeptide and a GxxxG motif in the beta
      polypeptide.

PMID- 15740754
TI  - Bacteriophages--potential for application in wastewater treatment processes.
AB  - Bacteriophages are viruses that infect and lyse bacteria. Interest in the ability
      of phages to control bacterial populations has extended from medical applications
      into the fields of agriculture, aquaculture and the food industry. Here, the
      potential application of phage techniques in wastewater treatment systems to
      improve effluent and sludge emissions into the environment is discussed. Phage
      mediated bacterial mortality has the potential to influence treatment performance
      by controlling the abundance of key functional groups. Phage treatments have the
      potential to control environmental wastewater process problems such as: foaming
      in activated sludge plants; sludge dewaterability and digestibility; pathogenic
      bacteria; and to reduce competition between nuisance bacteria and functionally
      important microbial populations. Successful application of phage therapy to
      wastewater treatment does though require a fuller understanding of wastewater
      microbial community dynamics and interactions. Strategies to counter host
      specificity and host cell resistance must also be developed, as should safety
      considerations regarding pathogen emergence through transduction.

PMID- 15740755
TI  - Plastics additives in the indoor environment--flame retardants and plasticizers.
AB  - Phthalic acid esters and phosphororganic compounds (POC) are generally known as
      semivolatile organic compounds (SVOCs) and are frequently utilized as
      plasticizers and flame retardants in commercial products. In the indoor
      environment, both compound groups are released from a number of sources under
      normal living conditions and accumulate in air and dust. Therefore, inhalation of
      air and ingestion of house dust have to be considered as important pathways for
      the assessment of exposure in living habitats. Especially in the case of very
      young children, the oral and dermal uptake from house dust might be of relevance
      for risk assessment. A critical evaluation of indoor exposure to phthalates and
      POC requires the determination of the target compounds in indoor air and house
      dust as well as emission studies. The latter are usually carried out under
      controlled conditions in emission test chambers or cells. Furthermore, chamber
      testing enables the determination of condensable compounds by fogging sampling.
      In the case of automobiles, specific scenarios have been developed to study
      material emissions on a test stand or to evaluate the exposure of users while the
      vehicle is driving. In this review, results from several studies are summarized
      and compared for seven phthalic esters and eight POC. The available data for room
      air and dust differ widely depending on investigated compound and compartment.
      Room air studies mostly include only a limited number of measurements, which
      makes a statistical evaluation difficult. The situation is much better for house
      dust measurements. However, the composition of house dust is very inhomogeneous
      and the result is strongly dependent on the particle size distribution used for
      analysis. Results of emission studies are presented for building products,
      electronic equipment, and automobiles. Daily rates for inhalation and dust
      ingestion of phthalic esters and POC were calculated from 95-percentiles or
      maximum values. A comparison of the data with results from human biomonitoring
      studies reveals that only a small portion of intake takes place via the air and
      dust paths.

PMID- 15740756
TI  - Road sediment: characterization and implications for the performance of vegetated
      strips for treating road run-off.
AB  - Increasing pressure to mitigate pollution from urban stormwater and road run-off
      is generating interest in vegetative treatment systems. The treatment performance
      of these systems depends on the characteristics of the pollutants entering them-
      for example, whether metals are dissolved or particle bound, and the particle
      size. This study sought to provide information on the characteristics of sediment
      derived specifically from road-use activities. A length of roadside gutter was
      vacuumed repeatedly at 2-day intervals. The samples obtained were found to
      contain predominantly fine particles (52% <250 microm). Particles <250 microm had
      the highest metal contents: 181-212 mg Cu/kg, 1073-2080 mg Zn/kg and 251-334 mg
      Pb/kg. A high percentage of the total metal load was associated with particles
      smaller than 125 microm (64% of Zn, 57% of Cu and 46% of Pb). These <125-microm
      particles are generally predicted to be poorly trapped by vegetation. In this
      study, these smaller particles were also found to have a lower density (<2200
      kg/m3) than normally modelled for sediment (>2600 kg/m3), and this may further
      reduce predicted trapping efficiencies. The impact of sediment entering
      vegetative treatment systems via aerial deposition is also discussed in terms of
      evaluating such systems for treatment performance.

PMID- 15740757
TI  - Inadvertent exposure to organochlorine pesticides DDT and derivatives in people
      from the Canary Islands (Spain).
AB  - In 1998, one of the largest determinations of organochlorine pesticides in a
      representative sample of a Spanish population (682 serum samples from the Canary
      Islands) was made in the context of the "Canary Islands Nutrition Survey" (ENCA).
      In the Canary Islands, extensive farming areas have been developed in these last
      decades, with greenhouses dedicated to intensive cultivation using DDT in huge
      amounts. In Spain, similarly to other European countries, DDT was banned in the
      late 1970s. The pesticide residues in human serum are indicative of past and
      present exposure to them. Our objective is to point out the differences of
      pesticide contamination between islands; and together with this, if a connection
      could be established with gender, age, or habitat of subjects. Concentration of
      selected persistent organochlorine pollutants (p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'
      DDE, p,p'-DDD, and o,p'-DDD) was measured with gas chromatography-electron
      capture detector. Almost all of the samples (99.3%) presented detectable levels
      of some DDT-derivatives, being p,p'-DDE the most frequently detected
      organochlorine. The median concentration of total DDT body burden, expressed in
      ng/g fat, present in the Canary Islands (370 ng/g fat) was similar to that found
      in other European countries, although it was noteworthy that a fourth of the
      population showed a total DDT body burden higher than 715 ng/g. Interestingly,
      statistical significant differences were found in serum levels of organochlorine
      pesticides between islands, being these levels higher in people from Tenerife and
      Gran Canaria (415 and 612 ng/g fat, respectively), the islands that present both
      highest population and highest surface devoted to intensive agriculture. As
      expected, serum levels of both total DDT body burden and p,p'-DDE increased with
      age. Statistically significant differences were also found in relation to gender,
      women showing higher levels of these organochlorine pesticides than men. One of
      the most relevant findings of this work is the presence of a very high DDT/DDE
      ratio in people from the Canary Islands, thus indicating a chronic exposure to
      DDT that persists nowadays. DDT and its derivatives are considered as
      xenoestrogens, and they have been linked to breast cancer. Having into account
      that the Canary Islands present high incidence and mortality for breast cancer,
      our results point to the possibility that these environmental contaminants may be
      playing a determining role that must be investigated in detail. The high levels
      of DDT and its derivatives in serum from people living in this Archipelago should
      be considered a matter of public health concern.

PMID- 15740758
TI  - Indoor radon levels in selected hot spring hotels in Guangdong, China.
AB  - Guangdong is one of the provinces that have most hot springs in China, and many
      hotels have been set up near hot springs, with spring water introduced into the
      bath inside each hotel room for hot spring bathing to attract tourists. In the
      present study, we measured radon in indoor and outdoor air, as well as in hot
      spring waters, in four hot spring hotels in Guangdong by using NR-667A (III)
      continuous radon detector. Radon concentrations ranged 53.4-292.5 Bq L(-1) in the
      hot spring water and 17.2-190.9 Bq m(-3) in outdoor air. Soil gas intrusion,
      indoor hot spring water use and inefficient ventilation all contributed to the
      elevated indoor radon levels in the hotel rooms. From the variation of radon
      levels in closed unoccupied hotel rooms, soil gas intrusion was found to be a
      very important source of indoor radon in hotel rooms with floors in contact with
      soils. When there was spring water bathing in the bathes, average radon levels
      were 10.9-813% higher in the hotel rooms and 13.8-489% higher in bathes compared
      to their corresponding average levels when there was no spring water use. Spring
      water use in the hotel rooms had radon transfer coefficients from 1.6x10(-4) to
      5.0x10(-3). Radon in some hotel rooms maintained in concentrations much higher
      than guideline levels might thus have potential health risks to the hotel
      workers, and technical and management measures should be taken to lower their
      exposure of radon through inhalation.

PMID- 15740759
TI  - Crop-specific human exposure assessment for polycyclic aromatic hydrocarbons in
      Czech soils.
AB  - Polycyclic aromatic hydrocarbons (PAH) are pollutants frequently found in soils,
      particularly in urban areas. From polluted soils, the PAH can be taken up into
      crops and the consumption of these crops can result in a human health risk. We
      estimated the bioconcentration factors (BCF) in the edible plant tissues for PAH
      using crop-specific models for leafy vegetables, root vegetables, potatoes and
      tree fruits. The estimates were compared with results from the empirical
      regression of Travis and Arms (T&A) for above-ground vegetation. The comparison
      shows that the use of crop-specific models resulted in lower BCF values of
      pollutant concentrations in fruits, potatoes and leafy vegetables, particularly
      for the heavier PAH (M>220 g mol(-1)). However, the crop-specific models yielded
      higher BCF values for root vegetables (carrot) and leafy vegetables if the
      attached soil particles (1%) were considered. Consequently, the average daily
      intake of benzo(a)pyrene (BaP) by an adult Czech through fruits and vegetables
      was estimated with the crop-specific models to be 190 ng BaP per person, and 460
      ng BaP per person with the T&A regression, for a soil concentration of 1 mg BaP
      kg(-1) soil (wet wt.). A virtually safe oral dose of BaP, as a marker of the
      carcinogenic PAH, was suggested by a European expert commission to be below 4.2
      to 35 ng per person and day. Using these figures, an acceptable soil
      concentration of BaP was estimated for the purpose of crop production to be below
      0.02 or 0.18 mg kg(-1) (wet wt.) with the crop-specific models, and below 0.01 or
      0.08 mg kg(-1) (wet wt.) with T&A. The results demonstrate clearly the advantage
      of the crop-specific exposure assessment: it can be adapted to different food
      baskets and allows more effective risk assessment and management of soil
      pollution.

PMID- 15740760
TI  - Wild boar hair (Sus scrofa) as a non-invasive indicator of mercury pollution.
AB  - This paper investigates the usefulness of wild boar (Sus scrofa) hair as a non
      invasive indicator of mercury pollution. Samples were collected in two hunting
      seasons (1998/1999 and 1999/2000) by hunters from four differently polluted
      regions of Poland. Mercury content was determined by AAS methods. Different
      washing procedures were compared. De-ionised water was found to be suitable for
      the removal of exogenous mercury sources in hair analysis. Metal distribution
      along hair was analysed. It was found that problems arising from differences in
      distribution of metal along a single hair strand as well as differences in the
      hair colour can be eliminated through the careful homogenisation of the samples
      before analysis. The influences of physiological, ecological and environmental
      factors that might significantly affect the obtained results (age, gender,
      season, location of habitat and diet of the sampled animals) were estimated and
      taken into account. The present study revealed that female hair contained a
      higher amount of mercury than male hair. Moreover the highest mercury content was
      found in young individuals between 1 and 2 years of age. A positive correlation
      of the present results with environmental data taken from the State Offices
      showed an influence of environmental pollution on the mercury level in wild boar
      hair.

PMID- 15740761
TI  - Impacts of zooplankton composition and algal enrichment on the accumulation of
      mercury in an experimental freshwater food web.
AB  - There is a well documented accumulation of mercury in fish to concentrations of
      concern for human consumption. Variation in fish Hg burden between lakes is often
      high and may result from differences in Hg transfer through lower levels of the
      food web where mercury is bioconcentrated to phytoplankton and transferred to
      herbivorous zooplankton. Prior research derived patterns of mercury accumulation
      in freshwater invertebrates from field collected animals. This study provides
      results from controlled mesocosm experiments comparing the effects of zooplankton
      composition, algal abundance, and the chemical speciation of mercury on the
      ability of zooplankton to accumulate mercury from phytoplankton and transfer that
      mercury to planktivores. Experiments were conducted in 550-L mesocosms across a
      gradient of algal densities manipulated by inorganic nutrient additions.
      Enriched, stable isotopes of organic (CH3(200HgCl)) and inorganic (201HgCl2)
      mercury were added to mesocosms and their concentrations measured in water,
      seston, and three common zooplankton species. After 2 weeks, monomethylmercury
      (MMHg) concentrations were two to three times lower in the two copepod species,
      Leptodiaptomus minutus and Mesocyclops edax than in the cladoceran, Daphnia
      mendotae. All three zooplankton species had higher MMHg concentrations in
      mesocosms with low versus high initial algal abundance. However, despite higher
      concentrations of inorganic mercury (HgI) in seston from low nutrient mesocosms,
      there were no significant differences in the HgI accumulated by zooplankton
      across nutrient treatments. Bioaccumulation factors for MMHg in the plankton were
      similar to those calculated for plankton in natural lakes and a four-compartment
      (aqueous, seston, macrozooplankton, and periphyton/sediments) mass balance model
      after 21 days accounted for approximately 18% of the CH3(200Hg) and approximately
      33% of the 201Hg added. Results from our experiments corroborate results from
      field studies and suggest the importance of particular zooplankton herbivores
      (e.g., Daphnia) in the transfer of Hg to higher trophic levels in aquatic food
      webs.

PMID- 15740762
TI  - Trace elements in fruiting bodies of ectomycorrhizal fungi growing in Scots pine
      (Pinus sylvestris L.) stands in Poland.
AB  - The trace metal contents in fruiting bodies of ectomycorrhizal (ECM) fungi,
      symbiotic partners of Scots pine, were studied on three sites situated in west
      central Poland. Elements were determined by atomic absorption spectrometry in 123
      samples of 16 species. The study explored the differences in metal accumulation
      in relation to site, fungal species, age and part of the fruiting body and
      results were related to metal content in soil and plant material (roots and
      needles). Soil analysis revealed that results were obtained under environmental
      conditions not subject to strong anthropogenic pressure. Median metal
      concentrations did not differ disparately between sites, although the
      concentrations of each of the tested metals in the individual species varied to a
      large extent. Extremely high levels of Al with a large bioconcentration factor
      (BCF) were found in sporocarps of Thelephora terrestris. The spread between the
      highest and the lowest concentration (max/min) was very wide in Al, Cd and Pb and
      these elements may be considered to be absorbed preferentially by fruiting bodies
      of some species whereas Fe, Mn and Zn, with relatively low values of max/min, are
      normally absorbed by the majority of fungi. There was no clear relationship
      between caps and stipes in metal content. However, a tendency to higher metal
      concentration in the caps was observed. The metal content in young and older
      fruiting bodies of five different fungi was species dependent. In order to
      estimate the degree of accumulation of each element by plant and mushrooms,
      bioconcentration factors (BCFs) were calculated. In plant material (roots and
      needles), highest values of BCFs were noted for essential metals, like Zn and Mn.
      Lead showed a definite exclusion pattern (BCF below 1). In fruiting bodies of
      tested fungi, especially in Amanita muscaria, cadmium was the most intensively
      accumulated metal. Lead was excluded by plants but was accumulated or excluded by
      fungi depending on the species. The significance of mycological observation and
      quantification of the metal content in monitoring of the forest ecosystem is
      discussed.

PMID- 15740763
TI  - The potential for methane emissions from groundwaters of the UK.
AB  - Methane (CH4) is only a trace constituent of the atmosphere but an important
      greenhouse gas. Although groundwater is unlikely to be a major source of
      atmospheric CH4, its contribution to the CH4 budget of the UK has up to now been
      poorly characterised. Groundwater CH4 concentrations have been measured on 85
      samples from water-supply boreholes and a further eight from other miscellaneous
      water sources. Concentrations in abstracted groundwaters ranged from <0.05-42.9
      microg/l for Chalk, <0.05-22 microg/l for the Lower Greensand, 0.05-21.2 microg/l
      for the Lincolnshire Limestone and from <0.05-465 microg/l for the Triassic
      sandstone. Having the largest abstraction volume, the Chalk is likely to be the
      main UK groundwater contributor to global CH4 emissions. A calculation to
      estimate the total emissions of CH4 from water-supply groundwater sources based
      on the median and the maximum CH4 concentrations gave values of 2.2x10(-6) and
      3.3x10(-4) Tg/year. Estimates show groundwater contributes a maximum of 0.05% of
      all UK CH4 emissions and a further two orders of magnitude less in terms of the
      global CH4 budget. Other groundwater sources such as inflows to tunnels may have
      significantly higher CH4 concentrations, but the volume of water discharged is
      much lower and the overall amount of CH4 outgassed is likely to be of the same
      order as the aquifer release. The generally low concentrations of CH4 in
      groundwater supplies suggest no threat of explosion, although groundwater
      released by excavations remains a hazard.

PMID- 15740764
TI  - Long-term trend of chemical constituents in precipitation in Tokyo metropolitan
      area, Japan, from 1990 to 2002.
AB  - In order to understand the actual status and mechanism of acid rain, it is
      important to know the pH of precipitation and its chemical constituents on a
      continuous and regular basis over a wide area. This study examines acid rain over
      a wide area using an observational network in the Tokyo metropolitan area of
      Japan, and analyzes the major chemical constituents of every precipitation
      sample. Precipitation was collected continuously for a period of 12 years from
      June 1990 to May 2002 at several sampling sites in the Tokyo metropolitan area,
      and its pH and chemical constituent concentrations were measured. The average pH
      ranged from 4.23 to 4.62, clearly indicating acidification of precipitation over
      the entire Tokyo metropolitan area. A time-trend model was applied to describe
      temporal variations of chemical constituent concentrations, including annual
      change rate, seasonal variation, and precipitation effects. Seasonal and annual
      trends for the past 12 years were examined with the model, using the least
      squares method. Nonsea salt (nss)-Ca2+ shows a maximum value in early spring, a
      seasonality probably caused by calcium-rich particles in airborne yellow dust
      from Asia. Slightly decreasing annual trends of nss-SO4(2-) may correspond to the
      recent decreasing trend of atmospheric SO2 gas concentrations in the Tokyo
      metropolitan area. The annual trends of NO3-, NH4+, and nss-Ca2+ show a large
      site-to-site difference. The increasing NO3-, NH4+, and nss-Ca2+ concentrations
      at inland suburban sites may be caused by increases in their local sources such
      as vehicle traffic and municipal waste incineration. The annual change rate of H+
      is slightly negative or almost zero at every site, so the acidification of
      precipitation has not become worse since 1990 over the Tokyo metropolitan area.

PMID- 15740765
TI  - Multi-route trihalomethane exposure in households using municipal tap water
      treated with chlorine or ozone-chlorine.
AB  - In Korea, data for multi-route trihalomethane (THM) exposure in households using
      municipal tap water treated with ozone-chlorine or chlorine are unavailable or
      very limited. Accordingly, the present study was designed to obtain those data by
      measurements of the THM concentrations in the tap water and indoor and outdoor
      air in the two types of households, along with an estimation of THM exposure from
      water ingestion, showering, and the inhalation of indoor air. Chloroform was the
      most abundant THM in all three media, yet no bromoform was detected in any
      sample. Similar to previous findings, the winter chloroform concentration in tap
      water treated with chlorine (22.1 microg/l, median) was significantly higher than
      that in the tap water treated with ozone-chlorine (16.8 microg/l, median).
      However, the summer water chloroform concentrations and summer and winter water
      concentrations of the other two THMs (bromodichloromethane and
      dibromochloromethane) exhibited no significant difference between the chlorine
      and ozone-chlorine-treated water. It was suggested that the effects of the water
      parameters including biochemical oxygen demand of raw water entering water
      treatment plants should be considered when evaluating the advantage of ozone
      chlorine disinfection for THM formation over chlorine disinfection. The indoor
      air THM concentration trend was also consistent with the water concentration
      trend. The indoor to outdoor air concentration ratios were comparable with
      previous studies. The THM exposure estimates from water ingestion, showering, and
      the inhalation of apartment indoor air when not in the shower suggested that, for
      residents living in the surveyed households, their exposure to THMs in the home
      was mostly associated with their household water uses. The THM exposure estimates
      from tap water ingestion were similar to those from showering.

PMID- 15740766
TI  - Metal contamination of soils and crops affected by the Chenzhou lead/zinc mine
      spill (Hunan, China).
AB  - In 1985, the collapse of the tailing dam in Chenzhou lead/zinc mine (Hunan,
      southern China) led to the spread of mining waste spills on the farmland along
      the Dong River. After the accident, an urgent soil cleaning up was carried out in
      some places. Seventeen years later, cereal (rice, maize, and sorghum), pulses
      (soybean, Adzuki bean, mung bean and peanut), vegetables (ipomoea, capsicum, taro
      and string bean) and the rooted soils were sampled at four sites: (1) the mining
      area (SZY), (2) the area still covered with the mining tailing spills (GYB), (3)
      the cleaned area from mining tailing spills (JTC), and (4) a background site
      (REF). Metal concentrations in the crops and soils were analyzed to evaluate the
      long-term effects of the spilled waste on the soil and the potential human
      exposure through food chains. The results showed that the physical-chemical
      properties of the soils obviously changed due to the different farming styles
      used by each individual farmer. Leaching effects and plant extraction of metals
      from some soils were quite weak. Certain soils were still heavily polluted with
      As, Cd, Zn, Pb and Cu. The contamination levels were in the order of GYB>SZY>JTC
      showing that the clean-up treatment was effective. The maximum allowable
      concentration (MAC) levels for Chinese agricultural soils were still highly
      exceeded, particularly for As and Cd (followed by Zn, Pb and Cu), with mean
      concentrations of 709 and 7.6 mg kg(-1), respectively. These concentrations
      exceed the MAC levels by 24 times for As and 13 times for Cd at GYB. Generally,
      the edible leaves or stems of crops were more heavily contaminated than seeds or
      fruits. Ipomoea was the most severely contaminated crop. The concentrations of Cd
      and Pb were 3.30 and 76.9 mg kg(-1) in ipomoea leaves at GYB, which exceeded the
      maximum permit levels (0.5 mg kg(-1) for Cd and 9 mg kg(-1) for Pb) by 6.6 and
      8.5 times, respectively. Taro (+skin) could accumulate high concentrations of Zn
      and Cd in the edible stem, and rice and capsicum had high Cd concentration in the
      edible parts. However, the toxic element concentrations in maize, sorghum, Adzuki
      bean, soybean and mung bean remained lower than the threshold levels. The bio
      accumulation factors (BAFs) of crops were in the order: Cd>Zn>Cu>Pb>As. BAF was
      typically lower in the edible seeds or fruits than in stems and leaves. The
      accumulation effect strongly depends on the crop's physiological properties, the
      mobility, of the metals, and the availability of metals in soils but not entirely
      on the total element concentrations in the soils. Even so, the estimated daily
      intake amount of Cu, Zn, Cd, and Pb from the crops grown in the affected three
      sites and arsenic at SZY and GYB exceeded the RDA (Recommended dietary allowance)
      levels. Subsequently, the crops grown in Chenzhou Pb/Zn mine waste affected area
      might have a hazardous effect on the consumer's health. This area still needs
      effective measures to cure the As, Cd, Pb, Zn and Cu contamination.

PMID- 15740767
TI  - Modeling the environmental fate of manganese from methylcyclopentadienyl
      manganese tricarbonyl in urban landscapes.
AB  - The environmental impacts of gasoline additives such as lead (Pb) and Methyl
      Tertiary Butyl Ether (MTBE) are well documented, leading to the phasing out of
      these additives. In contrast, little is known about the health and environmental
      impacts of potential replacement chemicals such as Methylcyclopentadienyl
      Manganese Tricarbonyl (MMT). The combustion of MMT in gasoline leads to the
      formation of MnPO4 and MnSO4 and MMT is considered a recent source of inorganic
      Mn in urban landscapes particularly in high traffic areas. The main objective of
      this study is to estimate the automotive deposition of Mn from MMT relative to
      the traffic volume at sites near a major highway in the Greater Toronto Area of
      Canada, where MMT is currently being used. Manganese emission levels were
      estimated for two sites that varied according to Annual Average Daily Traffic
      (AADT) density, fuel consumption, distance traveled by automobiles, and Mn
      concentration (mg l(-1)) in gasoline. Multiple regression analysis was used to
      predict the AADT volume from year 2002-2010. Comparison of the mass balance
      between the ANOVA means of 15% Mn emitted from the automobile tailpipes at 10,
      and 18 mg of Mn l(-1) in gasoline was conducted for both study sites. The
      percentage difference between the Mn input at the selected concentrations of Mn
      in gasoline and output into surface soil were found to be 99% significant for
      both sites. Thus the predicted 15% tailpipe emission levels for 10 mg of Mn l(-1)
      of gasoline used in automobiles, which represented 1290.03 g/year for site 1 and
      555.94 g/year for site 2, will add 5.73 and 2.47 mg/kg of Mn annually,
      respectively. These input levels are considered negligible when compared to the
      natural abundance of Mn in soil. Based on these data, it could take more than 95
      256 years of continuous MMT usage in the region to double the content of Mn in
      surface soils at the respective sites.

PMID- 15740768
TI  - Slow release chelate enhancement of lead phytoextraction by corn (Zea mays L.)
      from contaminated soil--a preliminary study.
AB  - Short-term enhancement of lead (Pb) and zinc (Zn) uptake by corn (Zea mays L.)
      seedlings from a contaminated soil was compared using slow-release coated EDTA
      granules-a coated chelating agent (CCA), uncoated EDTA granules, and EDTA
      solution in a greenhouse experiment. Soil Pb and Zn fractions were determined
      using a sequential extraction scheme. Release of the metals in the soil was
      examined in a column leaching study. After only 7 days of seedling growth, shoot
      biomass was decreased by all EDTA treatments compared with the zero-EDTA control.
      The amount of shoot biomass produced was highest with uncoated EDTA, intermediate
      with CCA, and lowest with the EDTA solution. Shoot Pb contents were highest with
      solid EDTA, intermediate with CCA, and lowest with EDTA solution, and they were
      always higher with EDTA treatments than in controls. In contrast, shoot Zn
      contents following EDTA treatments were lower than in the control. Levels of soil
      dissolved organic carbon (DOC) in aqueous soil extracts were much lower after CCA
      application than following treatments with solid EDTA and EDTA solution. After 17
      days of plant growth, when most of the chelating agent had been released from the
      CCA, soil organic carbon levels remained relatively constant and similar to those
      in the control, indicating that a relatively low chelating agent concentration
      can be maintained for the plants to take up the metals. The distribution of Pb in
      the sequential extraction procedure showed that the Pb level in the
      exchangeable+carbonate-bound fraction with CCA was significantly lower than that
      with solid EDTA or EDTA solution, further indicating that slow release of CCA
      improves the bioavailability of metals in the soil to match plant uptake of those
      metals. The results suggest that CCA can enhance shoot content of Pb but not of
      Zn from the contaminated soil in the short term, and may also reduce the risk of
      metal leaching from the soil.

PMID- 15740769
TI  - A comparison of the non-essential elements cadmium, mercury, and lead found in
      fish and sediment from Alaska and California.
AB  - Concentrations of three non-essential elements (cadmium (Cd), mercury (Hg), and
      lead (Pb)) were determined in sediment and fish from several locations in Alaska
      (AK) and California (CA) and used to examine differences in bioaccumulation
      within and between geographic locations. We analyzed tissue (liver, muscle, gill,
      and stomach contents) from white croaker (Genyonemus lineatus) and English sole
      (Pleuronectes vetulus) in California and flathead sole (Hippoglossoides
      elassodon) in Alaska, in addition to several species of invertebrates (mercury
      only). As found in previous work on arsenic (As) [Meador et al., 2004], Cd in
      fish liver exhibited a negative correlation with sediment concentrations. No such
      correlations were found for Hg and Pb when fish liver and sediment were compared;
      however, these metals did exhibit a positive relationship between liver and
      organic carbon normalized sediment concentrations, but only for the CA sites.
      Sediment concentrations of Hg at the AK sites were lower than those for the CA
      sites; however, AK invertebrates generally bioaccumulated more Hg than CA
      invertebrates. Conversely, Hg bioaccumulation was higher in CA fish. Even though
      ratios of total metal/acid volatile sulfides (AVS) in sediment were one to two
      orders of magnitude higher for the AK sites, bioaccumulation of these elements
      was much higher in fish from the CA sites. Bioaccumulation factors
      ([liver]/[sediment]) (BAFs) were highest at relatively clean sites (Bodega Bay
      and Monterey), indicating that elements were more bioavailable at these sites
      than from more contaminated locations. The observation of high BAFs for As in
      fish from Alaska and low BAFs for the California fish, but reversed for Cd, Hg,
      and Pb in this study, implies that differences in fish species are less important
      than the unique geochemical features at each site that control bioavailability
      and bioaccumulation and the potential sources for each element. Additionally,
      these data were also used to examine the metal depletion hypothesis, which
      describes the inverse relationship between elements and organic contaminants
      documented in some monitoring studies. Our results suggest that the enhanced
      bioavailability of the metals at some uncontaminated sites is the main
      determinant for the inverse correlation between metal and organic contaminants in
      tissue.

PMID- 15740770
TI  - Self-cleaning in an estuarine area formerly affected by 226Ra anthropogenic
      enhancements: numerical simulations.
AB  - A numerical model of the Odiel-Tinto estuary (Spain) has been developed to study
      the self-cleaning process that was evidenced from 226Ra measurements in water and
      sediments collected in the period 1999-2002, after direct releases from a
      fertilizer complex ceased (in 1998). The hydrodynamic model is first calibrated,
      and standard tidal analysis is carried out to calculate tidal constants required
      by the dispersion code to determine instantaneous water currents and elevations
      over the estuary. In this way, long-term simulations may be carried out. The
      dispersion code includes advective/diffusive transport of radionuclides plus
      exchanges with bottom sediments described through a kinetic approach. The
      dispersion model is first tested by comparing computed and measured 226Ra
      concentrations over the estuary resulting after releases in the Odiel and Tinto
      rivers. Next, it is applied to simulate the self-cleaning process of the estuary.
      The time evolution of radium concentrations in bed sediments is in generally good
      agreement with observations. The computed sediment halving time of the estuary is
      510 days, which also is in good agreement with that estimated from measurements.

PMID- 15740771
TI  - The influence of the Amazonian floodplain ecosystems on the trace element
      dynamics of the Amazon River mainstem (Brazil).
AB  - The purpose of this paper is to forecast the role of riverine wetlands in the
      transfer of trace elements. One of the largest riverine wetlands in the world is
      the floodplain (varzea) of the Amazon River and its tributaries (Junk and
      Piedade, 1997). The central Amazon wetlands are constituted by a complex network
      of lakes and floodplains, named varzeas, that extend over more than 300,000 km2
      (Junk, W.J., The Amazon floodplain--a sink or source for organic carbon? In
      Transport of Carbon and Minerals in Major World Rivers, edited by E.T. Degens, S.
      Kempe, R. Herrera, SCOPE/UNEP; 267-283, 1985.) and are among the most productive
      ecosystems in the world due to the regular enrichment in nutrients by river
      waters In order to understand if the adjacent floodplain of Amazon River have a
      significant influence on the trace element concentrations and fluxes of the
      mainstem, the concentrations of selected elements (i.e., Al, Mn, Fe, Co, Cu, Mo,
      Rb, Sr, Ba, and U) have been measured in the Amazon River water (Manacapuru
      Station, Amazonas State, Brazil) and in lake waters and plants (leaves) from a
      varzea(Ilha de Marchantaria, Amazonas State, Brazil) during different periods of
      the hydrological cycle. Four plant species (two perennial species: Pseudobombax
      munguba and Salix humboldtiana, and two annual herbaceous plants: Echinochloa
      polystachya and Eichhornia crassipes) were selected to represent the ecological
      functioning of the site. Time series obtained for dissolved Mn and Cu (<0.20
      microm) in Amazon River water could not be explained by tributary mixing or
      instream processes only. Therefore, the contribution of the waters transiting the
      floodplains should be considered. These results suggest that the chemical
      composition of the waters draining these floodplains is controlled by reactions
      occurring at sediment-water and plant-water interfaces. Trace elements
      concentrations in the plants (leaves) vary strongly with hydrological
      seasonality. Based on the concentration data and the biological productivity of
      floodplain ecosystems, a first order approximation of trace element storage
      (permanent or temporary) in the vegetation of these floodplains was made. It was
      found that floodplain-mainstem elemental fluxes make a significant contribution
      to the dissolved flux of the Amazon River. This study is part of the
      Brazilian_French joint research program Hybam (Hydrology and Geochemistry of the
      Amazonian Basin).

PMID- 15740772
TI  - Radioactive contamination of the Balchug (Upper Yenisey) floodplain, Russia in
      relation to sedimentation processes and geomorphology.
AB  - The radioactive contamination of a riverine floodplain, heavily influenced by
      discharges from Krasnoyarsk-26, has been studied with respect to sedimentation
      processes and the geomorphology of the Upper Yenisey floodplain. The study was
      effected by implementation of a regime of in situ observations and measurements,
      sampling, and the interpretation of satellite images. The results of the study
      indicate that on the Balchug Bypass Floodplain, radionuclide contamination is
      primarily influenced by the thickness of the deposited sediments, and the area
      can be considered as two depositional environments. The Balchug floodplain area
      was contaminated due to sedimentation of radionuclide-contaminated alluvium,
      whose depositional regime significantly changed after the construction of a
      hydroelectric power station in 1967. Contamination levels are lower on the
      upstream part of the floodplain where sediment depth is less than 0.2-0.3 m, and
      this contamination started to accumulate in 1967, while the downstream part of
      the floodplain, exhibiting deeper deposits, displays higher levels of
      radionuclide contamination because radionuclides began to deposit here in 1958
      when the Krasnoyarsk-26 Mining and Chemical Combine (KMCC) commenced operation.
      Radionuclide contamination of the floodplain is also related to the elevation of
      the floodplain, higher regions of the floodplain typically having lower
      contamination than low-lying areas, which tend to be frequently inundated with
      sediments being deposited during such inundations. Local relief, its orientation,
      and vegetation cover have also combined to form sediment traps with significantly
      higher radionuclide contamination. Lithological analysis combined with
      radiometric assay indicates a total 137Cs floodplain inventory of 33.7 GBq.

PMID- 15740773
TI  - Laser ablation ICP-MS profiling and semiquantitative determination of trace
      element concentrations in desert tortoise shells: documenting the uptake of
      elemental toxicants.
AB  - The outer keratin layer (scute) of desert tortoise shells consists of
      incrementally grown laminae in which various bioaccumulated trace elements are
      sequestered during scute deposition. Laser ablation ICP-MS examination of laminae
      in scutes of dead tortoises revealed patterns of trace elemental distribution
      from which the chronology of elemental uptake can be inferred. These patterns may
      be of pathologic significance in the case of elemental toxicants such as arsenic,
      which has been linked to both shell and respiratory diseases. Laser ablation
      transects, performed along the lateral surfaces of sectioned scutes, offered the
      most successful means of avoiding exogenous contamination that was present on the
      scute exterior. Semiquantitative determination of elemental concentrations was
      achieved using sulfur, a keratin matrix element, as an internal standard. The
      results presented here highlight the potential of laser ablation ICP-MS as a
      diagnostic tool for investigating toxic element uptake as it pertains to tortoise
      morbidity and mortality.

PMID- 15740775
TI  - A note on mercury levels in the hair of Alaskan reindeer.
AB  - Reindeer, as terrestrial herbivores, generally have low levels of Hg, but
      monitoring Hg levels can help in understanding ecological toxicity related to a
      changing environment. In this study, Alaskan reindeer were analyzed for total
      mercury (THg) in their hair. Both free-ranging reindeer from the Seward
      Peninsula, Alaska and reindeer fed a pollock-based fishmeal diet were surveyed.
      Free ranging reindeer had mean THg levels of (55.3 ng/g; n=5). The mean MeHg
      level in the free ranging reindeer was 45.5 (ng/g; n=5) or 79% of the THg level.
      The mean level for THg in the fishmeal fed reindeer was 19 ng/g (n=10). Younger
      reindeer (2 years of age or less) showed lower levels (0.8 ng/g, n=2) compared to
      adult reindeer (30.8 ng/g, n=6).

PMID- 15740774
TI  - The effect of exposure to employees from mining and milling operations in a
      uranium mine on lead isotopes--a pilot study.
AB  - Potential exposure during mining and milling of uranium ore has resulted in the
      industry being highly regulated. Exposure can arise from inhalation of the
      daughter product radioactive gas radon (222Rn), inhalation of radioactive dust
      particles from mining and milling, direct irradiation from outside the body, and
      ingestion of radionuclides (e.g. uranium or radium) in food or water. Making use
      of the highly unusual lead isotopic signature for uranium ores (high 206Pb/204Pb
      from the high uranium content, low 208Pb/204Pb from the low Th/U ratio), we
      undertook a pilot study of nine male mine employees and three controls from the
      Ranger uranium mine in the Northern Territory Australia to determine if it was
      feasible to use lead isotopes in blood to identify exposure to uranium-derived
      materials. The lead isotopic data for the mine employees and controls plot in two
      distinct fields which are consistent with predicted isotopic patterns. Assuming
      retention of 10% of the ingested lead, then the increases seen in 206Pb represent
      intakes of between 0.9 and 15 mg, integrated over the years of exposure. The
      small amount of lead does not affect blood lead concentrations, but appears to be
      sufficient to be detectable with sensitive isotopic methods. Further studies,
      including those on urine, should be undertaken to confirm the veracity of the
      lead isotope method in monitoring exposure of uranium industry employees.

PMID- 15740776
TI  - High exposure to arsenic from drinking water at several localities in eastern
      Croatia.
AB  - This study investigated the relationship between arsenic concentrations in
      drinking water in four towns/villages in eastern Croatia and corresponding hair
      arsenic concentrations of residents. The mean arsenic concentrations in community
      drinking water samples were 0.14, 37.88, 171.60, and 611.89 microg/l. The
      corresponding mean concentrations of the element in hair samples of subjects
      residing in each of the localities were 0.07 (n=11), 0.26 (n=17), 1.74 (n=11),
      and 4.31 microg/g (n=23). Chronic exposures to arsenic levels estimated in three
      investigated locations could present a serious health threat to around 3% of
      Croatian population.

PMID- 15740777
TI  - Effects of sodium nitroprusside, a nitric oxide donor, on gamma-aminobutyric acid
      concentration in the brain and on picrotoxin-induced convulsions in combination
      with phenobarbitone in rats.
AB  - The concentrations of nitric oxide (NO), the neuronal messenger molecule, and
      gamma-aminobutyric acid (GABA), the inhibitory neurotransmitter, and the activity
      of gamma-aminobutyric acid transaminase (GABA-T), the enzyme involved in the
      degradation of GABA, were measured in the brain of rats treated with graded doses
      (1.25, 2.5, 5.0 mg/kg) of sodium nitroprusside (SNP), the donor of NO. The effect
      of SNP was tested alone and in combination with phenobarbitone (PB), the GABA
      potentiating antiepileptic drug, against picrotoxin (PCT) (5 mg/kg)-induced
      convulsions in rats. The results of these studies showed that NO released from
      SNP (2.5 mg/kg) had a potential to inhibit GABA-T activity resulting in an
      increase in the concentration of GABA in the brain. Thus, SNP (2.5 mg/kg) was
      able to inhibit PCT-induced convulsions and was able to produce an additive
      anticonvulsant action with PB. However, a much greater increase in the
      concentration of NO by 5.0 mg/kg of SNP did not change the activity of GABA-T and
      the concentration of GABA, and promoted the convulsant action of PCT. These
      results suggest that a moderate increase in the concentration of NO following the
      administration of its donor SNP (2.5 mg/kg) results in an enhancement of the
      concentration of GABA in the brain and in an inhibition of PCT-induced
      convulsions independently and additively with PB and that a marked increase in NO
      concentration after the administration of a larger dose of SNP (5.0 mg/kg)
      results in proconvulsant action.

PMID- 15740778
TI  - Diurnal rhythms in quinpirole-induced locomotor behaviors and striatal D2/D3
      receptor levels in mice.
AB  - Dopaminergic drugs, including the D2/D3 agonist quinpirole, produce lasting
      changes in the brain that lead to altered behavioral responses. The action of
      these drugs is dosing time-dependent; in fruit flies, behavioral response to
      quinpirole shows a marked circadian variability. Here we demonstrate diurnal
      rhythm-dependent variations both in quinpirole-induced locomotor behaviors and in
      striatal D2 and D3 protein levels in mice. We found opposing diurnal rhythms in
      striatal D2 and D3 protein levels, resulting in a high D2/D3 ratio during the day
      and a low D2/D3 ratio at night. Protracted quinpirole treatment differentially
      altered striatal D2/D3 rhythms depending on the time of injection (i.e., day or
      night). When quinpirole-induced locomotor activity was analyzed for 90 min, we
      found hypomotility after the first day or nighttime drug injection. By the
      seventh injection, daytime quinpirole treatment produced clear hyperactivity
      while nighttime quinpirole treatment continued to induce a significant initial
      hypoactivity followed by a hyperactivity period. Our data indicate that
      quinpirole-induced long-term alterations in the brain include dosing time
      dependent changes in dopamine receptor rhythms. Therefore, we propose that
      diurnal mechanisms, which participate in drug-induced long-term changes in the
      dopamine system, are important for the development of dopaminergic behaviors.

PMID- 15740779
TI  - Cross-talk between an activator of nuclear receptors-mediated transcription and
      the D1 dopamine receptor signaling pathway.
AB  - Nuclear receptors are transcription factors that usually interact, in a ligand
      dependent manner, with specific DNA sequences located within promoters of target
      genes. The nuclear receptors can also be controlled in a ligand-independent
      manner via the action of membrane receptors and cellular signaling pathways. 5
      Tetradecyloxy-2-furancarboxylic acid (TOFA) was shown to stimulate transcription
      from the MMTV promoter via chimeric receptors that consist of the DNA binding
      domain of GR and the ligand binding regions of the PPARbeta or LXRbeta nuclear
      receptors (GR/PPARbeta and GR/LXRbeta). TOFA and hydroxycholesterols also
      modulate transcription from NF-kappaB- and AP-1-controlled reporter genes and
      induce neurite differentiation in PC12 cells. In CV-1 cells that express D(1)
      dopamine receptors, D(1) dopamine receptor stimulation was found to inhibit TOFA
      stimulated transcription from the MMTV promoter that is under the control of
      chimeric GR/PPARbeta and GR/LXRbeta receptors. Treatment with the D(1) dopamine
      receptor antagonist, SCH23390, prevented dopamine-mediated suppression of
      transcription, and by itself increased transcription controlled by GR/LXRbeta.
      Furthermore, combined treatment of CV-1 cells with TOFA and SCH23390 increased
      transcription controlled by the GR/LXRbeta chimeric receptor synergistically. The
      significance of this in vitro synergy was demonstrated in vivo, by the
      observation that SCH23390 (but not haloperidol)-mediated catalepsy in rats was
      potentiated by TOFA, thus showing that an agent that mimics the in vitro
      activities of compounds that activate members of the LXR and PPAR receptor
      families can influence D1 dopamine receptor elicited responses.

PMID- 15740781
TI  - Anxiolytic-like effect of a selective and non-peptidergic melanocortin 4 receptor
      antagonist, MCL0129, in a social interaction test.
AB  - The social interaction test is an animal behavioral test of anxiety. Brain
      melanocortins such as alpha-melanocyte stimulating hormone (alpha-MSH) and
      adrenocorticotropic hormone (ACTH) have anxiogenic effects in this test.
      Melanocortins have five receptor subtypes (MC1-MC5). Among them, MC3 and MC4
      receptor are mainly expressed in the brain. We investigated the involvement of
      MC4 receptor in a social interaction test, using Ac-[Nle(4),Asp(5),D
      Phe(7),Lys(10)]alpha-MSH-(4-10)-NH2 (MT II), an MC4 receptor agonist, and 1-[(S)
      2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen
      1-yl)butyl]piperazine (MCL0129), a selective and nonpeptide MC4 receptor
      antagonist. MT II dose-dependently and significantly reduced the time spent in
      social interaction. Acute administration of MCL0129 had no effect on the results
      of this test. In contrast, when given repeatedly for 1 week, MCL0129
      significantly and dose-dependently increased the time spent in social interaction
      without affecting locomotor activity. These results suggest that MC4 receptor is
      involved in social interaction, and that MCL0129, an MC4 receptor antagonist, has
      an anxiolytic-like effect in this model.

PMID- 15740780
TI  - Effects of clomipramine on self-control choice in Lewis and Fischer 344 rats.
AB  - Rates of delay discounting (impulsive choice) have been shown to vary among
      individuals, particularly people who abuse drugs relative to those who do not,
      but factors that may contribute to these differences have not been identified. To
      explore a role for possible genetic and neurochemical determinants, Lewis (n = 8)
      and Fischer 344 (n = 8) rats were allowed to choose between one food pellet
      delivered immediately and three food pellets delivered after increasing delays.
      The delays to the large reinforcer (0, 10, 20, 40, 60 s) were increased across
      five blocks of trials in daily experimental sessions. For both groups of rats,
      choice for the larger reinforcer decreased as the delay to presentation
      increased. However, the Lewis rats were more likely to choose the smaller,
      immediate reinforcer earlier in the session, i.e., at shorter large-reinforcer
      delays, than the Fisher 344 rats. This difference in choice was statistically
      significant. Repeated administration of 3.0 mg/kg, i.p. clomipramine (mean of
      last five sessions) did not significantly alter choice, relative to baseline, for
      either strain. The present findings suggest that differences in delay
      discounting/impulsive choice may involve genetic, e.g., neurochemical,
      differences.

PMID- 15740782
TI  - Antidepressant-like actions of intra-accumbens infusions of allopregnanolone in
      ovariectomized Wistar rats.
AB  - This study was aimed to verify the role of the nucleus accumbens (NAcc) in the
      antidepressant-like effects of allopregnanolone in ovariectomized rats forced to
      swim. The interaction between infusions of allopregnanolone (intra-NAcc) with
      systemic administrations of allopregnanolone, muscimol, fluoxetine and GABA-A
      antagonists was assessed. Results showed that allopregnanolone (intra-NAcc; 1.5
      microg, p < 0.05; 2.0 microg, p < 0.05) or systemic injections of
      allopregnanolone (1.5 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05; s.c.) or muscimol
      (0.3 mg/kg, p < 0.05; 0.6 mg/kg, p < 0.05; i.p.) reduced immobility by increasing
      climbing in the forced swimming task (FST), whereas fluoxetine (1.0 mg/kg, p <
      0.05; 2.0 mg/kg, p < 0.05; i.p.) reduced immobility by increasing swimming.
      Allopregnanolone (intra-NAcc; 0.5 microg/side) synergized with systemic doses of
      allopregnanolone (0.5 mg/kg; p < 0.05), muscimol (0.1 mg/kg; p < 0.05) or
      fluoxetine (0.5 mg/kg; p < 0.05) and reduced immobility by increasing climbing.
      Picrotoxin (0.125 mg/kg; i.p.) attenuated the synergism of the combination
      allopregnanolone (intra-NAcc; 0.5 microg/side) plus fluoxetine (i.p.) or
      allopregnanolone (s.c.) and the effects of allopregnanolone (intra-NAcc; 1.5
      microg/side). Bicuculline (2.0 mg/kg; i.p.) attenuated the synergism between the
      combination allopregnanolone (intra-NAcc; 0.5 microg/side) plus muscimol (i.p.),
      but not the synergism of the combination allopregnanolone (intra-NAcc; 0.5
      microg/side) plus allopregnanolone (s.c.). In conclusion, allopregnanolone
      (systemic injections or intra-NAcc), fluoxetine or muscimol produced
      antidepressant-like effects in the FST. Subthreshold doses of allopregnanolone
      (intra-NAcc) synergized with systemic subthreshold doses of fluoxetine, muscimol
      or allopregnanolone. Antagonists of the GABA-A receptor canceled the synergism.

PMID- 15740783
TI  - Differential behavioral and neuroendocrine effects of repeated nicotine in
      adolescent and adult rats.
AB  - Despite the high prevalence of tobacco abuse among adolescents, the neurobiology
      of nicotine addiction has been studied mainly in adult animals. Repeated
      administration of this drug to adult rats induces behavioral sensitization.
      Nicotine activates the HPA axis in adult rats as measured by drug-induced
      increases in ACTH and corticosterone. Both behavioral sensitization and
      corticosterone are implicated in drug addiction. We examined the expression of
      behavioral sensitization induced by nicotine as well as the changes in
      corticosterone levels after repeated injections of nicotine in adolescent and
      adult animals. Adolescent and adult rats received subcutaneous (s.c.) injections
      of saline or 0.4 mg/kg of nicotine once daily for 7 days. Three days after the
      last injection animals were challenged with saline or nicotine (0.4 mg/kg; s.c.).
      Nicotine-induced locomotion was recorded in an activity cage. Trunk blood samples
      were collected in a subset of adolescent and adult rats and plasma corticosterone
      levels were determined by radioimmunoassay. Adult, but not adolescent, rats
      expressed behavioral sensitization. Pretreatment with nicotine abolished
      corticosterone-activating effect of this drug only in adult animals, indicating
      the development of tolerance at this age. Our results provide evidence that
      adolescent rats exposed to repeated nicotine display behavioral and
      neuroendocrine adaptations distinct from that observed in adult animals.

PMID- 15740784
TI  - The involvement of central cholinergic system in (+)-matrine-induced
      antinociception in mice.
AB  - The antinociceptive effect of (+)-matrine was examined in mice by writhing, tail
      pressure and hot-plate tests. (+)-Matrine (5, 10 and 20 mg/kg s.c.) produced
      antinociception in a dose-dependent manner. In hot-plate test, the
      antinociception produced by (+)-matrine (10 mg/kg s.c.) was attenuated by
      muscarinic receptor antagonists atropine (5 mg/kg i.p.) and pirenzepine (0.1
      mug/mouse i.c.v.) and acetylcholine depletor hemicholinium-3 (HC-3) (1 mug/mouse
      i.c.v.), but not by opioid receptor antagonist naloxone (2 mg/kg i.p.), dopamine
      D(2) receptor agonist (-)-quinpirole (0.1 mg/kg i.p.) or catecholamine depletor
      reserpine (2.5 mg/kg i.p.). Radioligand binding assay demonstrated that (+)
      matrine had no affinity for mu-, kappa- or delta-opioid receptors in a wide
      concentration range (1 x 10(-11)-1 x 10(-3) M). The results suggest that (+)
      matrine exerts its antinociceptive effect through multiple mechanism(s) such as
      increasing cholinergic activation in the CNS rather than acting on opioid
      receptors directly.

PMID- 15740785
TI  - Anxiolytic-like actions of centrally-administered neuropeptide Y, but not
      galanin, in C57BL/6J mice.
AB  - Neuropeptide Y (NPY) and galanin (GAL) are densely localized in brain regions
      subserving stress, fear and anxiety. While previous research supports a role for
      both neuropeptides in the mediation of rodent emotional behaviors, there is
      currently a lack of information on the effects of central administration of NPY
      and GAL on fear- and anxiety-related behaviors in mice. In the present study, the
      effects of intracerebroventricularly administered NPY and GAL were assessed in
      C57BL/6J mice on a battery of tests for fear- and anxiety-related behavior. NPY
      (0.5, 1.0 nmol) produced clear anxiolytic-like effects in the elevated plus-maze
      and light<-->dark exploration test, whereas GAL (0.5, 1.0 nmol) was without
      effect. NPY (0.5 nmol) also increased locomotor activity in the open field test.
      In the fear conditioning paradigm, NPY administered prior to training reduced
      freezing to context (0.5, 1.0 nmol) and auditory cue (1.0 nmol). Pre-training GAL
      (0.5 nmol) treatment reduced freezing to context. Taken together, results
      demonstrate robust effects of centrally-administered NPY, but not GAL, on anxiety
      like behaviors and fear conditioning in mice. These findings provide a basis for
      future studies of mice with targeted gene mutations, directed at delineating the
      anatomical regions and receptor subtypes mediating the effects of NPY and GAL on
      emotion.

PMID- 15740786
TI  - Meal patterns in female rats during and after intermittent nicotine
      administration.
AB  - Previously we observed in male rats that intermittent administration of nicotine
      (NIC) during the dark phase reduces food intake (FI) by initially decreasing only
      dark phase meal size. This was followed several days later by an increase in dark
      phase meal frequency such that FI returned to normal, while body weight remained
      suppressed. Termination of NIC treatment resulted in a modest dark phase
      hyperphagia. Since some human females use NIC as a weight control drug, the
      present study investigated changes in FI and body weight regulation in adult
      female rats treated for five estrous cycles with saline or a 1.40 mg/kg/day (free
      base) dose of NIC, which was given in four equal i.p. doses during the dark
      phase. The rats were followed for 15 days after cessation of NIC. Initially both
      dark and light phase FI were reduced and this was caused by an immediate decrease
      in dark and light phase meal size; the attenuation of meal size continued after
      cessation of NIC. On day 7 of NIC, the rats compensated by significantly
      increasing the number of dark, but not light, phase meals they took. This
      resulted in a normal 24-h FI, which was caused by a dark phase increase in FI
      coupled with a continued decrease in light phase FI. Importantly, these changes
      in meal patterns persisted for some time after termination of NIC. Upon NIC
      cessation, the NIC group showed no hyperphagia even though their body weight was
      significantly decreased. These results document that administration of NIC during
      the dark phase resulted in a reorganization of the microstructure of FI in
      females rats that resembles, but does not exactly duplicate, that observed in
      male rats. Like males, long lasting alterations in the microstructure of FI
      (e.g., meal size and meal number), were noted in female rats for up to 2 weeks
      after cessation of NIC. These results differ from studies in which NIC was given
      continuously 24-h per day and indicate that dark phase NIC administration in rats
      may represent an appropriate model to study the impact of NIC on meal patterns.

PMID- 15740787
TI  - Chronic morphine exposure during puberty decreases postpartum prolactin secretion
      in adult female rats.
AB  - Opiate use in teenage populations has been increasing in recent years. The
      potential impact of exposure to high levels of opiates at a time when
      reproductive systems are maturing has not been well studied, especially in
      females. The present study used an animal model of adolescent opiate abuse in
      females to examine the potential impact of high levels of opiates during puberty
      on several reproductive parameters, including suckling-induced prolactin
      secretion. Two groups of juvenile female rats were administered increasing doses
      of morphine sulfate or saline (s.c.) from age 30-50 days, beginning with a dose
      of 2.5 mg/kg and achieving a maximal dose of 50 mg/kg. As adults, these females
      were mated and reared either their own or foster pups. On either postpartum day 5
      or 10, following a 4 h separation, suckling-induced prolactin secretion was
      measured. In addition, on postpartum day 5 maternal behavior latencies were
      determined. The results demonstrate reduced suckling-induced prolactin secretion
      on postpartum day 5 in females previously exposed to morphine during pubertal
      development. These effects were observed in females rearing either their own or
      fostered pups. These effects were not due to any differences in maternal behavior
      latencies, as retrieval or crouching latencies were unaffected. In summary,
      chronic morphine exposure during puberty results in changes in the regulation of
      prolactin secretion during early lactation, which are observed several weeks
      after cessation of drug treatment. These data suggest that prior opiate use
      during puberty can continue to affect the regulation of prolactin secretion into
      adulthood.

PMID- 15740788
TI  - Transdermal nicotine administration enhances automatic auditory processing
      reflected by mismatch negativity.
AB  - Mismatch negativity (MMN) is a component of event-related potentials (ERPs) with
      a wide-ranging applicability to the investigation of neuronal substrates of
      information processing in normal and psychopathological states. Nicotine has been
      shown to be implicated in the pathophysiology of psychiatric disorders as
      schizophrenia or Alzheimer's disease, and has also been proposed as a self
      administered drug in schizophrenia. The goal of the present study is to elucidate
      the effect of nicotine on the auditory automatic processing reflected by MMN.
      Nicotine was administered transdermally under controlled dosage. Ten healthy
      volunteers attended the laboratory for one baseline session and two test
      sessions. The test sessions involved administration of a placebo patch and a
      nicotine skin patch, which were counter-balanced. The ERPs were recorded
      passively during an auditory oddball paradigm. Nicotine administration shortened
      the MMN latencies, and these effects were independent of the earlier ERP
      components, N100 and P200. In conclusion, nicotine enhances preattentive and
      automatic processing such as MMN system and these effects appear to be quite
      specific and independent of earlier cognitive stages than preattentive mismatch
      processing. The shortened MMN latency may be interpreted as a reduction of the
      amount of time required to complete a neuronal mismatch process through the
      ascending auditory pathway.

PMID- 15740789
TI  - Alterations in GABAergic function following forced swimming stress.
AB  - Forced swimming induces alterations in the GABA brain concentration and could
      change the sensitivity of the GABA/benzodiazepine receptor-chloride ionophore
      complex to benzodiazepines. This change in sensitivity could be explained by the
      allopregnanolone release that takes place during stress. The current study was
      carried out to determine whether forced swimming is able to modify the anti
      anxiety effect of diazepam and to explore the possible relation of this change to
      allopregnanolone, the GABA concentration or/and the GABA/benzodiazepine receptor
      density. Unstressed and stressed mice, injected with the vehicle or diazepam,
      were evaluated in the exploratory behavior test. Diazepam induced clear
      anxiolytic actions at all doses in unstressed animals, but such an effect was not
      observed in stressed animals. The injection of allopregnanolone 24 h before the
      anxiety test blocked the effect of this benzodiazepine. Forced swimming decreased
      GABA concentrations in the hippocampus and the thalamus-hypothalamus region,
      besides decreasing the [(3)H]flunitrazepam labeling in both the hypothalamus and
      amygdala. These results show that forced swimming abolishes the anti-anxiety
      effect of diazepam.

PMID- 15740790
TI  - Morphine preexposure facilitates morphine place preference and attenuates
      morphine taste aversion.
AB  - Repeated morphine preexposure has been reported to enhance measures of morphine
      reward (conditioned place preference; CPP) and attenuate measures of morphine
      aversion (conditioned taste aversion; CTA). These effects are generally
      independently assessed, limiting the ability to determine if the enhancing and
      attenuating effects of morphine exposure are mediated by a common factor. To
      assess any potential relationship between these two effects, the present study
      examined the impact of morphine preexposure on these motivational properties of
      morphine using a combined CTA/CPP procedure in which the same animals receive
      concurrent taste and place conditioning. Specifically, male Sprague-Dawley rats
      were preexposed to morphine [5 mg/kg; subcutaneously (sc)] or equivolume drug
      vehicle. Following preexposure, animals were given saccharin to drink and
      injected with morphine sulfate (1 or 5 mg/kg sc) or drug vehicle (CTA).
      Immediately thereafter, they were placed on one side of a two-compartment chamber
      (CPP). On the next day, they were given water followed by injections of the
      drug's vehicle and then placed in the other compartment. There were four such
      conditioning cycles after each of which a CTA and CPP test were given. While
      preexposure to morphine attenuated morphine-induced CTAs, morphine-induced CPPs
      were enhanced within the same animals. These effects of morphine preexposure were
      dose- and time-dependent and parallel. These data indicate that the attenuating
      and sensitizing effects of morphine preexposure on taste aversions and place
      preferences, respectively, could be mediated by a common mechanism, although
      other possibilities for these effects of morphine preexposure remain.

PMID- 15740791
TI  - Interaction of cocaine and dopamine transporter inhibitors on behavior and
      neurochemistry in monkeys.
AB  - Drugs that target the dopamine transporter (DAT) have been proposed as
      pharmacotherapies to treat cocaine abuse. Accordingly, it is paramount to
      understand pharmacological interactions between cocaine and DAT inhibitors. The
      present study characterized acute interactions between cocaine and several DAT
      inhibitors (RTI-177, FECNT, RTI-112) that differed in selectivity for monoamine
      transporters on operant behavior and in vivo neurochemistry in squirrel monkeys.
      RTI-177 and FECNT, two DAT inhibitors with low affinity at norepinephrine
      transporters (NET), produced dose-dependent stimulant effects on behavior
      maintained by a fixed-interval schedule of stimulus termination. Compared to
      cocaine, RTI-177 and FECNT had a slower onset and longer duration of action. In
      vivo microdialysis in the caudate nucleus of awake monkeys confirmed dose
      dependent increases in extracellular dopamine that corresponded to behavioral
      effects. Among the drugs characterized, RTI-112 is reportedly the least selective
      for binding to DAT, NET, and serotonin transporters (SERT). Interestingly, RTI
      112 failed to produce significant behavioral-stimulant effects, and its effects
      on extracellular dopamine were highly variable across subjects. The results
      indicate that the pharmacological profile of DAT inhibitors may be influenced by
      actions at multiple monoamine transporters. Importantly, there was little
      evidence of additivity on behavioral or neurochemical measures when cocaine was
      administered in combination with behavioral-stimulant doses of the DAT
      inhibitors.

PMID- 15740792
TI  - The spinal nitric oxide involved in the inhibitory effect of midazolam on
      morphine-induced analgesia tolerance.
AB  - Previous studies had shown that pretreatment with midazolam inhibited morphine
      induced tolerance and dependence. The present study was to investigate the role
      of spinal nitric oxide (NO) in the inhibitory effect of midazolam on the
      development of morphine-induced analgesia tolerance. Subcutaneous injection of
      100 mg/kg morphine to mice caused an acute morphine-induced analgesia tolerance
      model. To develop chronic morphine tolerance in mice, morphine was injected for
      three consecutive days (10, 20, 50 mg/kg sc on Day 1, 2, 3, respectively). In
      order to develop chronic tolerance model in rats, 10 mg/kg of morphine was given
      twice daily at 12 h intervals for 10 days. Midazolam was intraperitoneally
      injected 30 min prior to administration of morphine. Tail-flick test, hot-plate
      and formalin test were conducted to assess the nociceptive response.
      Immunocytochemistry, histochemistry and western blot were performed to determine
      the effect of midazolam on formalin-induced expression of Fos protein,
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and nitric oxide
      synthase (NOS) in chronic morphine-tolerant rats, respectively. The results
      showed that pretreatment with midazolam significantly inhibited the development
      of acute and chronic morphine tolerance in mice, which could be partially
      reversed by intrathecal injection of NO precursor L-arginine (L-Arg). In chronic
      morphine-tolerant rats, pretreatment with midazolam significantly decreased the
      formalin-induced expression of Fos and Fos/NADPH-d double-labeled neurons in the
      contralateral spinal cord and NADPH-d positive neurons in the bilateral spinal
      cord. Both inducible NOS (iNOS) and neuronal NOS (nNOS) protein levels in the
      spinal cord were significantly increased after injection of formalin, which could
      be inhibited by pretreatment with midazolam. The above results suggested that the
      decrease of the activity and expression of NOS contributed to the inhibitory
      effect of midazolam on the development of morphine tolerance.

PMID- 15740793
TI  - Absence of 5-HT3 and cholinergic mechanisms in improgan antinociception.
AB  - Improgan, an analgesic derived from histamine antagonists, acts in the brain stem
      to activate descending non-opioid, pain-relieving circuits, but the mechanism of
      action of this drug remains elusive. Because improgan has a moderate affinity for
      5-HT(3) receptors, and, since cholinergic and serotonergic drugs can modulate
      descending analgesic circuits, roles for 5-HT(3), nicotinic and muscarinic
      receptors in improgan antinociception were presently investigated in rats.
      Improgan (80 microg, icv) induced nearly maximal inhibition of hot plate and tail
      flick nociceptive responses, and these actions we unaffected by antagonists of
      muscarinic (atropine, 5.9 mg/kg, i.p.) and nicotinic (mecamylamine, 2 mg/kg,
      i.p.) receptors. Control experiments verified that these antagonist treatments
      were maximally effective against muscarinic and nicotinic antinociception in both
      tests. In addition, improgan antinociception was unaffected by icv pretreatment
      with a 5-HT(3) antagonist (ondansetron, 20 microg). When given alone, icv
      treatment with neither this antagonist nor a 5-HT(3) agonist (m
      chlorophenylbiguanide, 1000 nmol, icv) modified thermal nociceptive latencies.
      These results show no role for supraspinal cholinergic and 5-HT(3) receptors in
      improgan antinociception. The findings help to narrow the search for the relevant
      mediators of the action of this novel analgesic agent.

PMID- 15740794
TI  - Effect of calcium channel modulators on temperature regulation in ovariectomized
      rats.
AB  - Clinical studies evaluating a calcium channel modulator, gabapentin, for the
      treatment of vasomotor symptoms have been reported. The present studies evaluated
      three calcium channel modulators in ovariectomized (OVX) rodent models of
      temperature regulation. Gabapentin, reported to interact with the alpha(2)delta
      subunit of voltage-sensitive calcium channels and the L-type voltage-gated
      calcium channel blockers, verapamil and nifedipine, were examined. These series
      of experiments demonstrated that orally administered gabapentin, verapamil and
      nifedipine all acutely and dose-dependently lower tail skin temperature in both
      models of OVX-induced thermoregulatory dysfunction. These compounds all had a
      rapid onset of action, however, the efficacy of all three calcium channel
      modulators is less than that observed following chronic estrogen treatment.
      Additionally, these compounds were also tested in a telemetric rat model
      measuring core body temperature to evaluate any temperature effects on internal
      core temperature. The present data suggests that gabapentin, verapamil and
      nifedipine all act to globally alter temperature regulation in steroid-dependent
      models of thermoregulatory function.

PMID- 15740795
TI  - Neurochemical, pharmacokinetic, and behavioral effects of the novel selective
      serotonin reuptake inhibitor BMS-505130.
AB  - BMS-505130 is a potent and selective serotonin transport inhibitor; K(i) for
      binding to the serotonin transporter = 0.18 nM (K(i) values for binding to the
      norepinephrine and dopamine transporters = 4.6 and 2.1 microM, respectively). In
      platelet serotonin uptake studies BMS-505130 (5 mg/kg, p.o.) produced a robust
      inhibition of serotonin uptake. In microdialysis studies oral dosing with BMS
      505130 produced a dose-dependent increase in cortical serotonin levels that
      reached a maximal effect of 200% above baseline at a dose of 1 mg/kg, p.o.; the
      peak serotonin response was transient in nature. Following oral administration,
      peak plasma concentrations of BMS-505130 reached Tmax at 1.6 +/- 0.7 h and then
      declined to concentrations <10% of Cmax within the following 6 h; plasma half
      life following i.v. dosing was 0.46 +/- 0.02 h. Parallel microdialysis and
      pharmacokinetic studies revealed that changes in serotonin levels in the cortex
      mirrored changes in the brain concentration of BMS-505130. In a behavioral assay
      known to be sensitive to selective serotonin reuptake inhibitors (SSRIs), mouse
      tail suspension, BMS-505130 produced a robust response after either oral or
      intraperitoneal dosing. BMS-505130 exhibits a pharmacological, neurochemical and
      behavioral profile consistent with a potent SSRI. Moreover, BMS-505130's short
      half-life may be advantageous for the treatment of premature ejaculation where an
      acute effect to delay ejaculation followed by a relatively rapid fall in SSRI
      plasma concentrations might be desirable.

PMID- 15740796
TI  - Stage-dependent fate determination of neural precursor cells in mouse forebrain.
AB  - Cortical neural precursor cells (NPCs) sequentially undergo expansion, neurogenic
      and gliogenic phases during development, although the underlying mechanisms are
      poorly understood. Recent studies have identified a number of extrinsic factors
      that regulate the fate of NPCs. For example, we have shown that Wnt signaling
      induces neuronal differentiation of NPCs in an instructive manner. Importantly,
      Wnt signaling does so in late stage (neurogenic phase) of NPCs but not in early
      stage (expansion phase) of NPCs. Instead, Wnt signaling promotes proliferation of
      early NPCs. Likewise, STAT3-activating ligands induce astrocytic differentiation
      in late (gliogenic phase) but not in early (expansion and neurogenic phases)
      NPCs. These stage-dependent responses of NPCs might play a central role in
      determining the timing of differentiation and the size of final population of
      each differentiated cell type.

PMID- 15740797
TI  - Chemorepulsion and cell adhesion molecules in patterning initial trajectories of
      sensory axons.
AB  - Research in the past decade has advanced our knowledge of the key role that
      diffusible cues play in axonal guidance during development. In higher
      vertebrates, dorsal root ganglion (DRG) neurons extend axons centrally to the
      spinal cord through the dorsal root entry zone and peripherally to muscle and
      skin targets. In this review, we focus on the role of proximate "non-target"
      tissues in the initial stages of DRG axonal growth. In the early stages of
      development, "non-target" tissues including the dermamyotome, the notochord, and
      the ventral spinal cord exert chemorepulsion for DRG axons. We describe how
      semaphorin 3A, chondroitin sulfate proteogrycans, and cell adhesion molecules
      participate in chemorepulsion and the way they provide spatio-temporal
      specificity to chemorepulsion. Axon chemorepulsion may act not only to shape DRG
      axonal trajectories but it also affects a variety of other axonal projections in
      the peripheral and central nervous system.

PMID- 15740798
TI  - MEG study on neural activities associated with syntactic and semantic violations
      in spoken Korean sentences.
AB  - We carried out an magnetoencephalography (MEG) study to record cortical responses
      elicited in the left hemisphere by ending verb phrases, which had syntactic or
      semantic anomalies, in Korean sentences of subject-object-verb order. Using the
      high temporal and spatial resolution of MEG, the study was aimed at identifying
      neural activities that occur during a latency course associated with the
      syntactic or semantic process in the spoken sentence. Major responses, distinct
      from the responses to normal sentences, were observed in two latency periods of
      about 400 and 600 ms following the onset of the verb phrase. Source localization
      of the grand average fields indicated separate activities in the inferior frontal
      region and the vicinity of the auditory cortex for the first 400-ms response to
      the syntactic anomaly. The region around the auditory cortex was indicated for
      the response to the semantic anomaly in a similar latency. The second 600-ms
      response indicated activity around the middle temporal gyrus inferior to the
      auditory cortex for both syntactic and semantic anomalies. The results are
      discussed with reference to the ERP components established for Indo-European
      languages, and the possibility of concurrent processing of syntactic and semantic
      aspects is suggested.

PMID- 15740799
TI  - Analysis of activity of motor units in the biceps brachii muscle after
      intercostal-musculocutaneous nerve transfer.
AB  - We examined respiratory activity of motor units (MUs) in the internal intercostal
      nerves (IICNs)-transferred biceps brachii muscle (IC-biceps) in cats. MUs of IC
      biceps showed respiratory discharges in inspiratory and expiratory phases, and
      these were enhanced by CO2 inhalation. Narrowing the airway also enhanced
      inspiratory and expiratory MUs activity. A mechanical load to the thorax
      immediately enhanced inspiratory MUs activity and weakened expiratory MUs
      activity. We analyzed the cross-correlation of MUs activity in interchondral
      muscle and IC-biceps to characterize the respiratory spinal descending inputs to
      motoneurons. We confirmed the short-term synchronization from interchondral
      muscles indicating divergence of a single respiratory presynaptic axon to
      thoracic motoneurons, but could not find synchronization from IC-biceps. The
      motor axonal conduction velocity (axonal CV) of IC-biceps MUs was lower than that
      of interchondral muscles. There was no correlation between the respiratory
      recruitment order of IC-biceps MUs and their axonal CV. These results indicate
      that IC-biceps shows the respiratory activities and afferent inputs from
      intercostal muscle spindles in the neighboring segments remain influential on
      activity of IC-biceps. In addition, the short-term synchronization from IC-biceps
      could not be found, suggesting that the intercostal nerve transfer alters the
      respiratory spinal descending inputs to thoracic motoneurons.

PMID- 15740800
TI  - Colocalization of mineralocorticoid receptor and glucocorticoid receptor in the
      hippocampus and hypothalamus.
AB  - We investigated the distribution and colocalization pattern of the two
      corticosteroid receptors, mineralocorticoid receptor (MR) and glucocorticoid
      receptor (GR), in the hippocampus and hypothalamus, the main target regions of
      corticosterone in the rat brain, using double immunofluorescence histochemistry
      in conjunction with specific polyclonal antibodies against MR and GR. In the
      hippocampus, MR- and GR-immunoreactivity (ir) were colocalized in CA1 and CA2
      pyramidal neurons and granule cells of the dentate gyrus, while only MR-ir was
      seen in the CA3 pyramidal neurons. Colocalization of MR- and GR-ir was also
      observed in the parvocellular region, but not in the magnocellular region of the
      paraventricular nucleus (PVN). Subcellular distribution of MR-ir was more
      cytoplasmic in comparison with that of GR-ir, while the ratio of cytoplasmic to
      nuclear distribution of these receptors was different among the regions. After
      adrenalectomy (ADX), the distribution pattern of both receptors was changed to
      cytoplasmic, although the degree of the change of distribution was different
      among each region. Replacement of corticosterone after ADX recovered the
      distribution pattern to that of the sham-operated animals. These results suggest
      that the balance of MR and GR in the cell underlies the potential regulation of
      corticosteroid through the hippocampus and hypothalamus.

PMID- 15740801
TI  - Cholecystokinin and substance P immunoreactive projections to the paraventricular
      thalamic nucleus in the rat.
AB  - Cholecystokinin (CCK) and substance P (SP) are thought to play an important role
      in a variety of stress responses. Both CCK- and SP-positive fibers innervating
      the thalamus are found principally in the midline nuclei, including the
      paraventricular thalamic nucleus (PVT), which has strong reciprocal connections
      with the medial prefrontal cortex. In the present study, we determined the source
      of the CCK- and SP-immunoreactive fibers to the PVT, employing combination of
      retrograde neuronal tracing and immunohistochemistry in the rat. The PVT
      projecting neurons showing CCK immunoreactivity were detected in the dorsomedial
      nucleus of the hypothalamus, and ventral mesencephalic periaqueductal gray,
      including the Edinger-Westphal nucleus and the dorsal raphe nucleus. Sources of
      SP afferents to the PVT were detected in the Edinger-Westphal nucleus, the
      mesopontine tegmentum and the medullary raphe nucleus. CCK- and SP-immunoreactive
      fibers may exert modulatory influence on the prefrontal cortical activity via the
      PVT and regulate behavioral components of stress-adaptation responses.

PMID- 15740802
TI  - Effects of injecting GABAergic agents into the medullary reticular formation upon
      swallowing induced by the superior laryngeal nerve stimulation in decerebrate
      cats.
AB  - The purpose of this study was to elucidate the role of the GABAergic system in
      the medullary reticular formation (MRF) in the control of swallowing. In acutely
      decerebrated cats (n = 12), swallowing was induced by electrical stimulation (0.3
      6 V at 10-20 Hz for 10-20 s every minute) applied to the superior laryngeal nerve
      (SLN). The stimulus intensity was adjusted so that swallowing was induced two or
      four times during the period of the stimulation. Bicuculline, a GABA(A) receptor
      antagonist, was then injected (0.10-0.15 microl, 5 mM) into the MRF through a
      stereotaxically placed glass micropipette. In a total of 62 injections, 19
      injections (30.6%) increased the frequency of SLN-induced swallowing when it was
      injected into the lateral part of the MRF corresponding to the nucleus
      reticularis parvocellularis (NRPv). In eight of the effective injections (42.1%)
      which increased the frequency of SLN-induced swallowing, SLN stimulation also
      induced coughing. With two injections, stimulation of the SLN-induced coughing
      but not facilitation of swallowing. On the other hand, an injection of 0.10-0.15
      microl of 5 mM muscimol, a GABA(A) receptor agonist, into the NRPv decreased the
      frequency of SLN-induced swallowing. These results suggest that the NRPv neurons
      which are responsible for evoking swallowing are under the tonic inhibitory
      control of the GABAergic system.

PMID- 15740803
TI  - Inhibitory, facilitatory, and excitatory effects of ATP and purinergic receptor
      agonists on the activity of rat cutaneous nociceptors in vitro.
AB  - Pathological pain is often associated with changed sympathetic nerve activities.
      It is known that sympathetic nerve endings release ATP as a co-transmitter of
      norepinephrine, but the effect of this ATP on the nociceptive system has not been
      properly studied in that the concentration range used in the previous studies was
      much higher than is expected in the surroundings of nociceptor terminals. We
      examined the effects of ATP, especially at low concentration (10(-5) M or less),
      on C-fiber polymodal receptor (CPR) activity using a rat skin-nerve preparation
      in vitro. We found for the first time that ATP inhibited the heat response of
      CPRs at low concentration (10(-5) M), but facilitated it at high concentration
      (10(-3) M). The former effect was mimicked by a P2X3 agonist, alpha,beta
      methylene ATP, at 10(-5) M, while the latter was mimicked by 2-methylthio ADP (a
      P2Y1 agonist) or UTP (a P2Y2 agonist) at 10(-3) M, suggesting that the former is
      mediated by P2X receptors and the latter by P2Y receptors. After repetitive heat
      stimuli, ATP-induced CPR excitation was increased (10(-5) to 10(-3) M), but none
      of the purinergic agonists induced CPR excitation in a magnitude comparable to
      that by ATP. Possible mechanisms for these effects were discussed.

PMID- 15740804
TI  - Two-dimensional neural activity mapping of the entire population of hippocampal
      CA1 pyramidal cells responding to fear conditioning.
AB  - The hippocampus is involved in the encoding, storage, and retrieval of memory.
      Here, we have developed a novel mapping method for detecting the distribution of
      neural activity of the entire population of pyramidal cells in the hippocampal
      CA1 and subiculum regions, where expression profiles of Arc mRNA were used as an
      indicator of neural activity. The spherical pyramidal cell layer of the intact
      hippocampus was flattened into a two-dimensional plane, which was then serially
      sectioned in parallel with the plane to make tangential sections. Tangential
      sections were hybridized with an Arc cRNA probe and Arc signals from serial
      tangential sections were stacked and displayed on a two-dimensional plane,
      allowing one to easily visualize the neural activity of all pyramidal cells. We
      applied this method to the hippocampus of rats that had experienced contextual
      fear conditioning, which requires hippocampal function. We observed a net shift
      of Arc signals from dorsal to ventral CA1/subiculum with an interval prolongation
      to reconditioning after the initial conditioning. The reconditioning-revealed
      shift may reflect a reorganization process, which takes place during the period
      between initial conditioning and reconditioning, in the CA1/subiculum neural
      network that represents the neural storage and/or retrieval of the contextual
      fear conditioning.

PMID- 15740806
TI  - Regulation of synaptic vesicle recycling by calcineurin in different vesicle
      pools.
AB  - The synaptic vesicles keep recycling by the processes of endocytosis and
      exocytosis to maintain the normal synaptic transmission. The synaptic vesicles
      are classified as the readily releasable pool (RRP) and the reserve pool (RP). In
      the endocytosis process, calcineurin (CaN), a Ca2+/calmodulin-dependent protein
      phosphatase, has been shown to play important roles. However, it is unclear about
      its roles in different vesicle pools. Here, we investigated the role of CaN in
      the regulation of vesicle recycling in the RRP and RP. Vesicle recycling was
      monitored by using fluorescent dyes FM1-43 and FM4-64 in the primary cultures of
      hippocampal neurons. Inhibition of CaN by FK506 and cyclosporin A suppressed the
      endocytosis in the RP, but not in the RRP. Inhibition of CaN also restrained the
      exocytic process triggered by 10 Hz stimulation, but had no effect on 3-5 Hz
      stimulation-induced exocytosis. FK506 also reduced the total vesicle pool size in
      the synaptic terminals. A synthesized CaN inhibitory peptide showed the similar
      effects as FK506 and cyclosporin A. These results revealed a novel mechanism that
      CaN plays critical roles in the distinct vesicle recycling processes.

PMID- 15740805
TI  - Preemptive analgesia by zaltoprofen that inhibits bradykinin action and
      cyclooxygenase in a post-operative pain model.
AB  - The post-operative pain state results from a barrage of primary afferent inputs
      exposed to products of tissue damage such as bradykinin and prostaglandins and
      the central sensitization by the continuing inputs. This provides the rationale
      for preemptive analgesia, whereby the blockade of primary afferent inputs prior
      to injury may result in a reduction of post-operative pain. 2-(10,11-dihydro-10
      oxo-dibenzo[b,f]thiepin-2-yl) propionic acid (zaltoprofen) is a unique compound
      that inhibits cyclooxygenase (COX) and exhibits anti-bradykinin activity. The
      present study evaluated the preemptive analgesic effect of zaltoprofen in a post
      operative pain model produced by plantar incision. When orally, but no
      intrathecally, administered 30 min prior to incision, zaltoprofen significantly
      increased the withdrawal threshold 2 h and 1-3 days after incision at 10 mg/kg.
      While the bradykinin B1 antagonist des-Arg10-HOE-140, the selective COX-1
      inhibitor SC-560, and the selective COX-2 inhibitor celecoxib did not affect post
      operative pain, the B2 antagonist HOE-140 dose-dependently relieved the post
      operative pain at 2-200 microg/kg with a time course similar to that of
      zaltoprofen. The B2 receptor mRNA was expressed in the hindpaw and the expression
      did not change before and 24 h after surgery. These results suggest that
      zaltoprofen produces the preemptive analgesic effect peripherally by blocking the
      B2 pathway.

PMID- 15740807
TI  - Effect of Brn-3a deficiency on primary nociceptors in the trigeminal ganglion.
AB  - Immunohistochemistry for substance P, somatostatin and vanilloid receptor subtype
      1 as well as receptors for somatostatin and opioids was performed on the
      trigeminal ganglion in wild-type and Brn-3a knockout mice at postnatal day 0. In
      wild-type mice, the trigeminal ganglion contained abundant substance P-,
      vanilloid receptor subtype 1-, sst2A receptor- and delta-opioid receptor
      immunoreactive neurons, while the ganglion had only a few mu-opioid receptor
      immunoreactive neurons. The Brn-3a deficiency had an effect on the cell size but
      not the number of substance P-immunoreactive neurons. In knockout mice, the
      proportion of small immunoreactive neurons markedly increased and that of medium-
      to large-sized immunoreactive ones correspondingly decreased (mean +/- S.D. =
      54.7 +/- 29.1 microm2, range = 10.9-220.8 microm2) compared to wild-type mice
      (mean +/- S.D. = 116.6 +/- 58.6 microm2, range = 27.3-400.7 microm2). As for
      vanilloid receptor subtype 1-immunoreactive neurons, the number and cell size was
      barely affected by the deficiency. On the other hand, the loss of Brn-3a caused a
      decrease in the number of sst2A receptor- or delta-opioid receptor-immunoreactive
      neurons (more than 95% reduction) and an increase in the number of mu-opioid
      receptor-immunoreactive neurons (9.3-fold increase). Somatostatin-immunoreactive
      neurons were not detected in the trigeminal ganglion of wild-type or mutant mice
      at postnatal day 0. The present study suggests that Brn-3a deficiency may have
      effects on the survival of trigeminal nociceptors and their expression of some
      neurochemical substances.

PMID- 15740808
TI  - Ictal dipole source analysis based on a realistic scalp-skull-brain head model in
      localizing the epileptogenic zone.
AB  - The objective of this study is to examine whether dipole modeling based on a
      realistic scalp-skull-brain head model (SSB/DT) is useful to localize the
      epileptogenic zone. Eight patients with surgically treated temporal lobe epilepsy
      were studied. Dipole locations and vector moments of ictal epileptiform
      activities were calculated by inverse solution methods. Accuracy of dipole
      locations were assessed by comparing with intracranial EEG. The patterns of ictal
      epileptiform activities were correlated with the dipole location and vector
      moment. Dipole locations of the peaks of ictal epileptiform activities estimated
      by SSB/DT showed good agreement with the epileptogenic foci determined by
      intracranial EEG. SSB/DT was able to discriminate between medial and lateral
      temporal epileptogenic foci. Two distinctive types of dipole vector moments,
      vertical and horizontal were noted. Vertical dipole vector moments corresponded
      to the medial temporal dipole source and horizontal dipole vector moments were
      corresponded to the lateral temporal dipole source. Useful clues to differentiate
      between medial and lateral temporal lobe epilepsy by the visual inspection of
      scalp EEG were found. SSB/DT is useful tool in the presurgical evaluation of
      patients with intractable epilepsy.

PMID- 15740809
TI  - Excitatory GABAergic synaptic potentials in the mesencephalic trigeminal nucleus
      of adult rat in vitro.
AB  - The mesencephalic trigeminal nucleus (MesV) contains the somata of primary
      afferent neurons innervating masticatory muscle spindles and the periodontal
      membrane. MesV afferent somata are unique in receiving synaptic inputs.
      Intracellular recordings in coronal pontine slices from adult rats were made from
      MesV neurons identified by having Cs-sensitive inward rectification and
      pseudounipolar morphology. Stimuli near the MesV evoked either a cluster of
      action potentials superimposed on a postsynaptic potential (PSP) or an antidromic
      spike at resting membrane potential (RMP). Membrane hyperpolarization revealed
      that each cluster of action potentials consisted of an antidromic spike and a
      subsequent PSP. Evoked PSPs in slices and miniature postsynaptic currents (mPSCs)
      recorded using whole-cell patch in dissociated MesV neurons were resistant to
      glutamate antagonists and strychnine but were reversibly abolished by 40 microM
      bicuculline. Superfusion of 1-10 mM GABA decreased input resistance and
      depolarized the membrane. Reversal potentials for evoked PSPs and GABA-induced
      depolarizations were similar and close to that for mPSCs which matched the Cl-
      equilibrium potential. Thus activation of synapses on MesV somata evokes
      GABAergic PSPs that generate action potentials at RMP in the adult. These data
      also indicate that primary afferent MesV neurons can act as interneurons in the
      central control of mastication.

PMID- 15740810
TI  - GABAergic neurons in inferior colliculus of the GAD67-GFP knock-in mouse:
      electrophysiological and morphological properties.
AB  - Utilizing slice preparations of GAD67-GFP knock-in mouse, in which GABAergic
      neurons are specifically labeled with GFP fluorescence, we studied
      electrophysiological characteristics of GABAergic neurons of IC by whole-cell
      patch clamp-recording combined with biocytin-intracellular-staining techniques.
      GABAergic neurons of IC fell into two distinct firing types; (1) tonic type
      neurons and (2) transient (phasic) type neurons. Tonic type neurons showed
      regularly repetitive discharge pattern in response to a long depolarizing current
      pulse (200 ms), and transient type neurons showed spike discharges just at the
      onset of current pulse. Most of neurons of both types showed depolarizing sag in
      response to hyperpolarizing current pulse, which were blocked by 0.1 mM ZD7288
      (Ih blocker). All two types of tonic neurons showed an AHP, which was blocked by
      Cd2+ (0.1 mM) and high concentration of apamin (2 microM). One of tonic type
      neurons (BP) revealed a long delay in spike onset or a longer first spike
      interval when they were stimulated from hyperpolarized potentials. The remaining
      tonic neurons (RS) did not show this property. Tonic type neurons were
      distributed in all region of IC. Morphologically, they were not identical;
      heterogeneous in somatic diameter, dendritic field size and its orientation. One
      of transient type neurons (Th-) revealed an AHP after the spike. The other
      transient type neurons (Th+) showed a depolarization hump after the spike, which
      were blocked by 0.1-0.2 mM Ni2+. Th+ type neurons were found only in the
      dorsolateral region of IC, having small dendritic field. Th+ type neurons are
      likely to be a distinct, homogenous group of GABAergic neuron in IC.

PMID- 15740811
TI  - The joint WHO/ICM/FIGO statement on skilled attendants at birth.

PMID- 15740812
TI  - Examining the evidence for The International Confederation of Midwives' essential
      competencies for midwifery practice.
AB  - OBJECTIVE: to present the evidence for inclusion of selected midwifery tasks
      (skills) as essential practice competencies for midwives throughout the world.
      The tasks addressed are those presented to the International Confederation of
      Midwives (ICM) Council of Delegates in 2002 for discussion and adoption, based on
      the fact that during field-testing, notable variance was encountered. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: evidence-based practice should be
      characterised by the use of best practices derived from rigorous research,
      combined with and balanced by client perspectives and the expert judgement based
      on the critical thinking of the clinician. Much of midwifery practice is
      considered an art based on common sense, tradition, and woman-centred approaches
      to caring, as most of the women who seek midwifery care are healthy and require a
      health-promotion model of care that may not easily lend itself to examination by
      scientists or clinicians. However, when intervention is indicated to save the
      lives of mother, baby, or both, those interventions must be based on the best
      available evidence from a variety of sources leading to the most effective
      choices for action. The ICM Essential Competencies for Midwifery Practice (2002)
      are based on evidence derived from a variety of quantitative and qualitative
      methodologies. Expert clinical consensus may serve as to the best form of
      evidence at certain points in the evolution of knowledge. Every midwife needs to
      understand where the gaps exist in supporting traditional practices that have yet
      to be fully examined in a scientific manner. In summary, a multi-matrix or
      triangulated approach may be most appropriate to the delineation of evidence
      underpinning best midwifery practice.

PMID- 15740813
TI  - A case study of volunteers providing labour and childbirth support in hospitals
      in Canada.
AB  - OBJECTIVE: to document the process and outcome of an attempt to combine and
      institutionalise two grassroots health programmes that provided trained
      volunteers to support women through labour and childbirth in hospital. DESIGN: a
      qualitative, descriptive, comparative case study of programmes, with data
      collected through in-depth individual interviews with key informants and document
      review. SETTING: a Regional Health Authority in Canada. PARTICIPANTS: 16 women,
      from various stakeholder groups, with knowledge about the programmes. FINDINGS:
      despite considerable effort expended, the unified regional programme was not
      realised. This research highlights contextual factors that were salient for the
      programme's implementation. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      complex individual, interpersonal and institutional factors needed to be
      acknowledged but were not addressed in programme planning. This research may be
      relevant to policy and decision makers considering expansion of grassroots or
      community programmes to regional levels of service.

PMID- 15740814
TI  - The childbirth expectations of a self-selected cohort of Western Australian
      women.
AB  - OBJECTIVES: to explore and describe the labour and birth expectations of a cohort
      of Western Australian women, and to identify the factors that influence these
      expectations. DESIGN: a qualitative study using an explorative descriptive design
      and techniques associated with constant comparison. Data were collected from tape
      recorded telephone interviews. SETTING: : Perth, Western Australia. PARTICIPANTS:
      two hundred and two women who were pregnant or who had birthed within the last 12
      months. FINDINGS: five major themes were identified. Three of the five themes
      reflected a positive outlook on birth. These were labelled, 'owning and believing
      in birth as a natural event', 'satisfaction with the birth process and outcome'
      and 'involvement and participation in the birthing experience'. The remaining two
      themes 'birth is a negative event' and 'birth is a medical event' encapsulated
      the women's statements that described childbirth as a potential negative and
      unaffirming experience. Particularly influential on the formation of childbirth
      expectations were the public and private discourses of childbirth, especially
      those related to books and magazines, and the stories of mothers and sisters.
      Professional discourses, women's own history, and factors such as age and life
      style choices also influenced decisions and contributed to how women perceived
      their experiences. IMPLICATIONS FOR PRACTICE: the findings of the study challenge
      the anecdotal evidence that many contemporary western women willingly and
      knowingly choose or expect birth to be a medicalised event. Although midwives and
      other maternity healthcare providers need to help women develop realistic
      expectations, there is also a need to examine the influence of healthcare
      professionals in perpetuating a technical approach to birth. The findings do,
      however, confirm that some women are anxious, scared and frightened of the
      childbirth experience. It is essential that research continues to focus on
      developing strategies to assist women confront and deal with these fears.

PMID- 15740815
TI  - How do women identify health professionals at birth in Ghana?
AB  - OBJECTIVE: the percentage of births attended by health professionals is widely
      used to measure skilled attendance. This indicator is based on women's reports of
      their birth attendant. This study explores how women identify health
      professionals attending their births. DESIGN: exit interviews, focus groups, in
      depth interviews and a community survey. Qualitative data were analysed by topic.
      Frequency of women's responses on how they identify the birth attendant and other
      characteristics of birth care were generated through the community survey.
      SETTING AND PARTICIPANTS: women in Ghana who had birthed with a health
      professional in the last 5 years. MEASUREMENTS AND FINDINGS: role, prior
      knowledge and uniform are the most common means by which women identify their
      attendant. These means of identification do not distinguish accurately between
      different types of health professional. Delivery events are more complex than is
      suggested through use of the indicator 'percentage of deliveries with health
      professionals'. Fifty-five per cent of births were attended by more than one
      person. In 11.6% of births, women were attended only after the partial birth of
      their baby. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: there is potential for
      incorrect identification of birth attendant by the use of women's reports. None
      of the methods used could verify women's reporting. Methodological developments
      in this area are necessary along with improved recording systems. Opportunities
      for women to identify health professionals should be enhanced.

PMID- 15740816
TI  - Swedish and Middle-Eastern-born women's beliefs about gestational diabetes.
AB  - OBJECTIVE: to compare beliefs about health and illness between women born in
      Sweden and the Middle East who developed gestational diabetes (GD). DESIGN: a
      qualitative, explorative study using semi-structured interviews. SETTING: in
      hospital diabetes specialist clinic in Sweden. PARTICIPANTS: consecutive sample
      of women with GD; 13 born in Sweden and 14 born in the Middle East. MEASUREMENT
      AND FINDINGS: all the women described health as freedom from disease, and
      expressed worries for the baby's health and well-being. Women from the Middle
      East did not know the cause of GD, discussed the influence of social factors,
      such as being an immigrant, and supernatural factors, tried to adapt to the
      disease and thought it would disappear after birth, felt they had more pregnancy
      related complications but had not received any treatment. Swedish women
      attributed GD to inheritance, environment and hormonal change, feared developing
      Type 2 diabetes, found work-related stress harmful to their health, more often
      sought help, used medications against pregnancy-related complications, and were
      more often on sick-leave from work. KEY CONCLUSIONS: Swedish women initiated a
      battle against GD, demanded medical treatment for pregnancy-related complications
      because of gainful employment and viewed pregnancy as a disease. Women from the
      Middle East temporarily adapted to the disease and perceived pregnancy and
      related problems as a natural part of life. IMPLICATIONS FOR PRACTICE: it is
      important to assess individual beliefs, risk awareness and to meet individual
      needs for information.

PMID- 15740817
TI  - What do midwives and nurses in Turkey know about nutrition in the first six
      months of life.
AB  - OBJECTIVE: to discover what midwives and nurses in Turkey know and advise about
      nutrition in the first 6 months of life. DESIGN: a descriptive, cross-sectional
      study. SETTING: health clinics and mother and baby health and family planning
      centres in the municipality of Ankara. PARTICIPANTS: 301 midwives and nurses
      selected by stratified, random sampling. FINDINGS: nine questions related to the
      features and benefits of breast milk. The mean number of questions answered
      correctly was 7.55 (standard deviation [SD]=1.25). Participants agreed that the
      babies should be breast fed for the first 6 months of life (n=184; 61.1%) and
      that complementary food could be introduced at 6 months of age (n=291; 96.7%).
      Most participants (n=223; 74.1%) recommended that mothers who have to resume work
      should express and store breast milk, and their babies should be fed with it.
      Many participants noted that there may be one or more situations when artificial
      milk should be given in the first 6 months of life (n=286; 95.0%). Almost all of
      the participants (n=292; 97.0%) gave one or more suggestions of when breast milk
      was sufficient or insufficient. CONCLUSIONS: most midwives and nurses in this
      research had adequate knowledge related to babies in the first 6 months of life.
      However, with continuing education, knowledge deficits can be corrected, and
      awareness of their roles and responsibilities can be increased in achieving one
      of Turkey's priority goals for the 21st Century, that of decreasing the baby
      death rate.

PMID- 15740818
TI  - A randomised controlled trial in the north of England examining the effects of
      skin-to-skin care on breast feeding.
AB  - OBJECTIVE: to examine the effect of early skin-to-skin contact between mothers
      and their healthy full-term babies on initiation and duration of breast feeding.
      DESIGN: a randomised controlled trial comparing skin-to-skin with routine care.
      SETTING: Warrington Hospital, Cheshire, UK. PARTICIPANTS: 204 mother and baby
      pairs; 102 randomised to each group. OUTCOME MEASURES: success of first breast
      feed, maternal satisfaction with skin-to-skin care and preference for future post
      delivery care, baby-body temperature 1 hr after birth, partial or exclusive
      breast feeding at 4 months. FINDINGS: in the skin-to-skin group, 89 out of 98
      (91%) babies had a successful first feed compared with 82 out of 89 (83%) in the
      routine care group. The difference in the success rate was 8%, 95% confidence
      interval (CI) (-1.6%, 17.6%); chi(2)=2.7; df=1; P=0.10. Forty-two out of 97 (43%)
      babies given skin-to-skin were partially or exclusively breast feeding at 4
      months compared with 40 out of 100 (40%) of babies in the routine care group. The
      difference in breast-feeding rate at 4 months was 3.3%, 95% CI (-10.3%, 16.7% );
      chi(2)=0.22; df=1; P=0.64. The mean temperature 1 hr after birth was higher with
      skin-to-skin than routine care. The difference in means was 0.15 degrees C; 95%
      CI (0.03, 0.28); P=0.02. A larger proportion of mothers (87/97 [90%]) were very
      satisfied with skin-to-skin care, compared with 60 out of 102 (59%) in the
      control group; 83 out of 97 (86%) of the mothers in the intervention group said
      that they would prefer to receive the same care in the future compared with 31
      out of 102 (30%) mothers in the control group. CONCLUSIONS: the difference
      between the groups in the success rate for the first breast feed and rates at 4
      months was not statistically significant. However, mothers who had skin-to-skin
      contact enjoyed the experience, and most reported that they would choose to have
      skin-to skin care in the future. In this, the largest trial to date, previous
      concerns about baby-body temperature after skin-to-skin care were dispelled.

PMID- 15740819
TI  - Confidence intervals and Newcombe's method - what are they?

PMID- 15740820
TI  - A local study of childbearing Bangladeshi women in the UK.
AB  - OBJECTIVE: to examine the circumstances, experiences and needs of a local sample
      of low-income, childbearing women of Bangladeshi origin in the UK. DESIGN:
      qualitative interviews using a semi-structured questionnaire to obtain the
      interviewees' own accounts of the period around the birth of a baby. SETTING: a
      deprived area in the City of Leeds in the North of England. PARTICIPANTS: nine
      women of Bangladeshi origin who were pregnant or had a baby under 1 year of age
      were interviewed as part of a larger study of the needs and experiences of 52 low
      income, childbearing women. The nine women were recruited from a neighbourhood
      project set up to respond to the needs of Sylheti-speaking women with limited
      English fluency in the area. FINDINGS: the women's constrained material
      circumstances limit their access to resources, services and good health. This is
      related to their limited education, qualifications and English fluency. The lack
      of an adequate income particularly affects families with new babies. However,
      their relatively positive experiences of maternity care and benefit claim,
      compared with women with similar characteristics in other studies, may be related
      to access to advice, support and concrete help offered by the neighbourhood
      project. IMPLICATIONS FOR PRACTICE: social and health research, policy and
      practice might address information and support needs of low-income Bangladeshi
      women around the birth of a baby, and systematically take forward the idea of
      providing and evaluating integrated services, language support and advocacy
      between voluntary and state agencies.

PMID- 15740821
TI  - Current trends in women's health research: it is time to strike up the band as we
      march forward into the 21st century.

PMID- 15740822
TI  - More frequent partner hugs and higher oxytocin levels are linked to lower blood
      pressure and heart rate in premenopausal women.
AB  - In animals, ventral stroking for >5 days increases oxytocin (OT) activity and
      decreases blood pressure (BP), but related human studies are few. Thus,
      relationships between self-reported frequency of partner hugs, plasma OT and BP
      levels were examined in 59 premenopausal women before and after warm contact with
      their husbands/partners ending with hugs. Higher baseline OT before partner
      contact was associated with lower BP and heart rate, and met criteria to be a
      partial mediator of the lower resting BP shown by women reporting more frequent
      hugs (P<0.05). OT levels during post-contact stress were unrelated to hugs or BP.
      Menstrual cycle phase did not influence any OT measure. Thus, frequent hugs
      between spouses/partners are associated with lower BP and higher OT levels in
      premenopausal women; OT-mediated reduction in central adrenergic activity and
      peripheral effects of OT on the heart and vasculature are pathways to examine in
      future research.

PMID- 15740823
TI  - Maternal psychophysiological change during the second half of gestation.
AB  - This study investigated the trajectory of physiological and psychological
      functioning during the second half of pregnancy and compared responsiveness to a
      laboratory stressor between pregnant and non-pregnant women. Monitoring of 137
      pregnant women at 20, 24, 28, 32, 36, and 38 weeks of pregnancy included measures
      of heart period (HP), heart period variability (HPV), skin conductance (SCL),
      respiratory period (RP), respiratory sinus arrhythmia (RSA), and self-report of
      mood disturbance. HP and RSA declined during this period; SCL and mood
      disturbance increased. Parity was a significant moderator. HP and SCL
      responsiveness to the Stroop color-word task was assessed twice in pregnant
      participants and compared to a sample of 27 non-pregnant women. Physiologic
      responsiveness was reduced in pregnant women. Pregnant women perceived the Stroop
      to be more difficult, but performance was unaffected. Despite buffered
      responsivity to stressful stimuli during pregnancy, advancing gestation is
      associated with escalating sympathetic tone and declining parasympathetic tone.

PMID- 15740824
TI  - Influence of hormone therapy on the cardiovascular responses to stress of
      postmenopausal women.
AB  - Epidemiological and psychophysiological data suggest that groups that differ in
      reproductive hormones and stress responses also differ in risk for cardiovascular
      disease. To evaluate the effects of hormone therapy on women's cardiovascular
      responses to laboratory stressors, 89 healthy postmenopausal women were tested
      twice, before and after exposure for about 8 weeks to one of the five conditions:
      placebo, Estratab (primarily estrone), Estratab plus Prometrium (micronized
      progesterone), Estratab plus Provera (synthetic progestin), and Estratest (same
      estrogen as in Estratab plus methyltestosterone). Results showed that women
      assigned to Estratab plus Prometrium and Estratest had diminished systolic blood
      pressure responses to stress upon retesting, whereas the other groups did not
      change in the level of their responses. Women assigned to Estratab plus
      Prometrium had diminished diastolic blood pressure responses during a speech
      stressor upon retesting, whereas women assigned to Estratab plus Provera
      increased. Our findings show that hormone therapy does affect women's stress
      responses, but they do not provide a simple explanation as to why groups at high
      and low risk for cardiovascular disease differ in reproductive hormones and
      stress responses.

PMID- 15740825
TI  - Multiple stressors and coronary disease in women. The Stockholm Female Coronary
      Risk Study.
AB  - We proposed that double exposure to stressors at work and from family are
      associated with increased coronary risk in women and that the same exposures are
      accompanied by depressive feelings. The study group comprised 292 women coronary
      patients (30-65 years) and 292 age-matched healthy controls. Work-stress, marital
      stress, and depressive symptoms were assessed by standardized questionnaires and
      evaluated in both case-control and 5-year follow-up analyses. We found that
      double exposure to stress from work and family was accompanied by the highest
      risk and the worst prognosis in women's coronary disease. In women patients
      depressive feelings were frequent, and they were more closely related to family
      than to work stress. In healthy women, both stressors, but in particular their
      combination, lead to depressive symptoms.

PMID- 15740826
TI  - Social stress-associated depression in adult female cynomolgus monkeys (Macaca
      fascicularis).
AB  - This paper describes a behavior pattern in adult female cynomolgus monkeys that
      has several behavioral and physiological characteristics in common with human
      depression including reduced body fat, low levels of activity, high heart rate,
      hypothalamic-pituitary-adrenal (HPA) axis disturbances, and increased mortality.
      Under certain circumstances, this depressive behavior appears more common in
      socially stressed subordinate, than dominant, females. This is the first animal
      model of social stress-related depression in females and the first primate model
      of adult depression. It is important to have a female animal model of depression
      because women are more likely to experience a clinically significant depression
      than men, and depression in women is often associated with changes in
      reproductive system function. This model is particularly useful because these
      monkeys have menstrual cycles that are similar to those of women, and those that
      exhibit depressive behavior have relatively low levels of ovarian steroids. These
      monkeys may be a useful model of reproductive system-associated mood disorders in
      females.

PMID- 15740827
TI  - The relationship between fatigue and quality of life and inflammation during
      anthracycline-based chemotherapy in breast cancer.
AB  - Chemotherapy for breast cancer leads to increased fatigue, poor mood, and reduced
      quality of life. Few studies have examined possible changes in inflammation
      during chemotherapy as potential contributors to this phenomenon. This study
      examined the relationship among circulating levels of soluble intercellular
      adhesion molecule-1 (sICAM-1), vascular endothelial growth factor (VEGF) and
      interleukin-6 (IL-6) and fatigue, depressed mood, and quality of life before and
      during anthracycline-based chemotherapy. Twenty-nine women diagnosed with stage I
      IIIA breast cancer (mean age 49.5 years, S.D.+/-11) were studied prior to cycle 1
      of chemotherapy and 2.5 months later at the start of cycle 4 of chemotherapy.
      Chemotherapy led to a significant increase in sICAM-1 (P<0.05) and VEGF (P<0.01)
      levels, as well as increased ratings of fatigue (P<0.01), depressed mood
      (P<0.03), and poorer quality of life (P<0.01). Multiple regression analyses
      revealed that elevated VEGF (P<0.01) and sICAM-1 (P<0.02) were related to the
      increased fatigue and/or poorer quality of life as a result of chemotherapy. Pre
      chemotherapy levels of VEGF and pre-chemotherapy ratings of quality of life
      predicted quality of life in response to chemotherapy (P<0.001). The findings
      contribute to the literature by showing that both pre-chemotherapy and
      chemotherapy-induced changes in inflammation are related to changes in fatigue
      and quality of life in response to chemotherapy.

PMID- 15740828
TI  - Sex-related psychological predictors of baseline pain perception and analgesic
      responses to pentazocine.
AB  - Sex differences in pain perception and analgesic responses have garnered
      increasing attention in recent years. We examined the association of
      psychological factors to baseline pain perception and pentazocine analgesia among
      49 healthy women and 39 men. Subjects completed psychological questionnaires
      measuring positive and negative affect as well as catastrophizing. Subsequently,
      responses to experimental pain were assessed before and after double-blind
      administration of intravenous pentazocine (0.5mg/kg). In correlational analyses,
      positive affect predicted lower pain sensitivity among men but not women.
      Negative affect predicted lower baseline pain tolerances among both sexes but
      predicted poorer analgesia only among men. Catastrophizing was associated with
      greater pain sensitivity and less analgesia more consistently in men than women.
      Regression models revealed that positive affect predicted lower overall pain
      sensitivity and catastrophizing predicted poorer overall analgesic responses
      among men, while no significant predictors of overall pain or analgesia emerged
      for women. Moreover, positive affect and catastrophizing were negatively and
      positively correlated, respectively, with side effects from the medication, but
      only among men. These findings indicate sex-dependent associations of
      psychological factors with baseline pain perception, analgesic responses, and
      medication side effects.

PMID- 15740829
TI  - Sex differences in HPA axis responses to stress: a review.

PMID- 15740830
TI  - Modeling positive regulatory feedbacks in cell-cell interactions.
AB  - Our current understanding of molecular mechanisms of cellular regulation still
      does not support quantitative predictions of the overall growth kinetics of
      normal or malignant tissues. However, discernment of the role of growth-factor
      mediated cell-cell communication in tissue kinetics is possible by the use of
      simple mathematical models. Here we discuss the design and use of mathematical
      models in quantifying the contribution of autocrine and paracrine (i.e., humoral)
      interactions to the kinetics of tissue growth. We present models that include a
      humorally mediated regulatory feedback among cells built into phenomenological
      mathematical models of growth. Application of these models to data exemplifies
      the finite contributions of positive feedback in cell-cell interactions to the
      overall tissue growth. In addition, we propose a perturbation approach to allow
      separation of cell-cell interactions dependent on the perturbing agent (such as
      hormone antagonists in hormone-dependent tissues) from cell-cell interactions
      independent of it.

PMID- 15740831
TI  - Role of two toxin-producing plankton and their effect on phytoplankton
      zooplankton system--a mathematical study supported by experimental findings.
AB  - Plankton is the basis of the entire aquatic food chain. Phytoplankton, in
      particular, occupies the first trophic level. Plankton performs services for the
      Earth: it serves as food for marine life, gives off oxygen and also absorbs half
      of the carbon dioxide from the Earth's atmosphere. The dynamics of a rapid (or
      massive) increase or decrease of plankton populations is an important subject in
      marine plankton ecology and generally termed as a 'bloom'. Harmful algal blooms
      (HABs) have adverse effects on human health, fishery, tourism, and the
      environment. In recent years, considerable scientific attention has been given to
      HABs. Toxic substances released by harmful plankton play an important role in
      this context. In this paper, a mathematical model consisting of two harmful
      phytoplankton and zooplankton system will be discussed. The analytical findings
      will be verified through our experimental observations which were carried out on
      the eastern part of Bay of Bengal for the last three years.

PMID- 15740832
TI  - Spike trains in a stochastic Hodgkin-Huxley system.
AB  - We consider a standard Hodgkin-Huxley model neuron with a Gaussian white noise
      input current with drift parameter mu and variance parameter sigma(2). Partial
      differential equations of second order are obtained for the first two moments of
      the time taken to spike from (any) initial state, as functions of the initial
      values. The analytical theory for a 2-component (V,m) approximation is also
      considered. Let mu(c) (approximately 4.15) be the critical value of mu for firing
      when noise is absent. Large sample simulation results are obtained for mu<mu(c)
      and mu>mu(c), for many values of sigma between 0 and 25. For the time to spike,
      the 2-component approximation is accurate for all sigma when mu=10, for sigma>7
      when mu=5 and only when sigma>15 when mu=2. When mu<mu(c), sigma must be large to
      induce firing so paths are always erratic. As the noise increases, the
      coefficient of variation (CV) has a well-defined minimum, and then climbs
      steadily over the range considered. If mu is just above mu(c), when the noise is
      small, paths are close to deterministic and the standard deviation and CV of the
      time to spike are small. As sigma increases, some very erratic paths (some almost
      oscillatory) appear, making the mean, standard deviation and CV of the spike time
      very large. These erratic paths start to have a large influence, so all three
      statistics have very pronounced maxima at intermediate sigma. When mu>>mu(c),
      most paths show similar behavior and the moments exhibit smoothly changing
      behavior as sigma increases. Thus there are a different number of regimes
      depending on the magnitude of mu relative to mu(c): one when mu is small and when
      mu is large; but three when mu is close to and above mu(c). Both for the Hodgkin
      Huxley (HH) system and the 2-component approximation, and regardless of the value
      of mu, the CV tends to about 1.3 at the largest value (25) of sigma considered.
      We also discuss in detail the problem of determining the interspike interval and
      give an accurate method for estimating this random variable by decomposing the
      interval into stochastic and almost deterministic components.

PMID- 15740833
TI  - Avoiding overfitting in multilayer perceptrons with feeling-of-knowing using self
      organizing maps.
AB  - Overfitting in multilayer perceptron (MLP) training is a serious problem. The
      purpose of this study is to avoid overfitting in on-line learning. To overcome
      the overfitting problem, we have investigated feeling-of-knowing (FOK) using self
      organizing maps (SOMs). We propose MLPs with FOK using the SOMs method to
      overcome the overfitting problem. In this method, the learning process advances
      according to the degree of FOK calculated using SOMs. The mean square error
      obtained for the test set using the proposed method is significantly less than
      that in a conventional MLP method. Consequently, the proposed method avoids
      overfitting.

PMID- 15740834
TI  - An interdisciplinary approach to certain fundamental issues in the fields of
      physics and biology: towards a unified theory.
AB  - Recent experiments appear to have revealed the possibility of the existence of
      quantum entanglement between spatially separated human subjects. In addition, a
      similar condition might exist between basins containing human neurons adhering to
      printed circuit boards. In both instances, preliminary data indicates what appear
      to be non-local correlations between brain electrical activities in the case of
      the human subjects and also non-local correlations between neuronal basin
      electrical activities, implying entanglement at the macroscopic level. If the
      ongoing expanded research and the analysis of same continues to support this
      hypothesis, it may then make it possible to simultaneously address some of the
      fundamental problems facing us in both physics and biology through the adoption
      of an interdisciplinary empirical approach based on Bell's experimental
      philosophy, with the goal of unifying these two fields.

PMID- 15740836
TI  - Is optimal solution of every NP-complete or NP-hard problem determined from its
      characteristic for DNA-based computing.
AB  - Cook's Theorem [Cormen, T.H., Leiserson, C.E., Rivest, R.L., 2001. Introduction
      to Algorithms, second ed., The MIT Press; Garey, M.R., Johnson, D.S., 1979.
      Computer and Intractability, Freeman, San Fransico, CA] is that if one algorithm
      for an NP-complete or an NP-hard problem will be developed, then other problems
      will be solved by means of reduction to that problem. Cook's Theorem has been
      demonstrated to be correct in a general digital electronic computer. In this
      paper, we first propose a DNA algorithm for solving the vertex-cover problem.
      Then, we demonstrate that if the size of a reduced NP-complete or NP-hard problem
      is equal to or less than that of the vertex-cover problem, then the proposed
      algorithm can be directly used for solving the reduced NP-complete or NP-hard
      problem and Cook's Theorem is correct on DNA-based computing. Otherwise, a new
      DNA algorithm for optimal solution of a reduced NP-complete problem or a reduced
      NP-hard problem should be developed from the characteristic of NP-complete
      problems or NP-hard problems.

PMID- 15740835
TI  - A mathematical model of combination therapy using the EGFR signaling network.
AB  - An increasing awareness of the significance of abnormal signal transduction in
      tumors and the concomitant development of target-based drugs to selectively
      modulate aberrantly-activated signaling pathways has given rise to a variety of
      promising new strategies in cancer treatment. This paper uses mathematical
      modeling to investigate a novel type of combination therapy in which multiple
      nodes in a signaling cascade are targeted simultaneously with selective
      inhibitors, pursuing the hypothesis that such an approach may induce the desired
      signal attenuation with lower doses of the necessary agents than when one node is
      targeted in isolation. A mathematical model is presented which builds upon
      previous theoretical work on EGFR signaling, simulating the effect of
      administering multiple kinase inhibitors in various combinations. The model
      demonstrates that attenuation of biochemical signals is significantly enhanced
      when multiple upstream processes are inhibited, in comparison with the inhibition
      of a single upstream process. Moreover, this enhanced attenuation is most
      pronounced in signals downstream of serially-connected target points. In
      addition, the inhibition of serially-connected processes appears to have a supra
      additive (synergistic) effect on the attenuation of downstream signals, owing to
      the highly non-linear relationships between network parameters and signals.

PMID- 15740837
TI  - Simulation of rat behavior by a reinforcement learning algorithm in consideration
      of appearance probabilities of reinforcement signals.
AB  - Brown and Wanger [Brown, R.T., Wanger, A.R., 1964. Resistance to punishment and
      extinction following training with shock or nonreinforcement. J. Exp. Psychol.
      68, 503-507] investigated rat behaviors with the following features: (1) rats
      were exposed to reward and punishment at the same time, (2) environment changed
      and rats relearned, and (3) rats were stochastically exposed to reward and
      punishment. The results are that exposure to nonreinforcement produces resistance
      to the decremental effects of behavior after stochastic reward schedule and that
      exposure to both punishment and reinforcement produces resistance to the
      decremental effects of behavior after stochastic punishment schedule. This paper
      aims to simulate the rat behaviors by a reinforcement learning algorithm in
      consideration of appearance probabilities of reinforcement signals. The former
      algorithms of reinforcement learning were unable to simulate the behavior of the
      feature (3). We improve the former reinforcement learning algorithms by
      controlling learning parameters in consideration of the acquisition probabilities
      of reinforcement signals. The proposed algorithm qualitatively simulates the
      result of the animal experiment of Brown and Wanger.

PMID- 15740838
TI  - On time-space of nonlinear phenomena with Gompertzian dynamics.
AB  - This paper describes a universal relationship between time and space for a
      nonlinear process with Gompertzian dynamics, such as growth. Gompertzian dynamics
      implicates a coupling between time and space. Those two categories are related to
      each other through a linear function of their logarithms. Moreover, we
      demonstrate that the spatial fractal dimension is a function of both scalar time
      and the temporal fractal dimension. The Gompertz function reflects the
      equilibrium of regular states, that is, states with dynamics that are predictable
      for any time-point (e.g., sinusoidal glycolytic oscillations) and chaotic states,
      that is, states with dynamics that are unpredictable in time, but are
      characterized by certain regularities (e.g., the existence of strange attractor
      for any biochemical reaction). We conclude that both this equilibrium and volume
      of the available complementary Euclidean space determine temporal and spatial
      expansion of a process with Gompertzian dynamics.

PMID- 15740840
TI  - A unified view of quiet and perturbed stance: simultaneous co-existing excitable
      modes.
AB  - When standing quietly, human upright stance is typically approximated as a single
      segment inverted pendulum. In contrast, investigations which perturb upright
      stance with support surface translations or visual driving stimuli have shown
      that the body behaves like a two-segment pendulum, displaying both in-phase and
      anti-phase patterns between the upper and lower body. Here we present evidence
      that a single-segment characterization of quiet stance is inadequate. Similar to
      perturbed stance, quiet stance has simultaneously co-existing in-phase and anti
      phase patterns. Subjects stood with eyes closed in three sensory conditions: a
      fixed surface, a foam surface, and a sway-referenced surface. Spectral analysis
      showed that the body behaved like a multi-link pendulum with two co-existing
      modes. The angles of the trunk and leg segments were in-phase for frequencies
      below 1 Hz and anti-phase for frequencies above 1Hz. The shift from in-phase to
      anti-phase sway showed an abrupt change for the fixed and foam surfaces, but a
      gradual change for the sway-referenced condition with the trunk showing a phase
      lead over the legs. The coexistence of in-phase and anti-phase patterns during
      quiet stance suggests that the ankle and hip strategies are not extremes along a
      behavioral continuum of mixed strategies. They are "simultaneously co-existing
      excitable modes", both always present, but one of which may predominate depending
      upon the characteristics of the available sensory information, task or
      perturbation.

PMID- 15740839
TI  - Potential for enlarging DNA memory: the validity of experimental operations of
      scaled-up nested primer molecular memory.
AB  - DNA is an attractive memory unit because of its immense information density.
      Here, we describe a memory model made of DNA, called Nested Primer Molecular
      Memory (NPMM). NPMM consists of many DNA strands, and each DNA strand consists of
      two areas: a data area and a data address area. When the address of target data
      is specified, only the target data can be extracted from NPMM. In this paper, we
      evaluate the validity of the basic operations of NPMM and then discuss the
      feasibility of scaled-up NPMM through some laboratory experiments. In the latter,
      we deal with scaled-up NPMM simulated by the Concentration Scaling method.

PMID- 15740841
TI  - The architecture of the tau haplotype block in different ethnicities.
AB  - We have assessed the pattern of the extended haplotype block over the tau gene
      which covers a region of approximately 2 Mb in different ethnicities. This
      analysis shows that the pattern of linkage disequilibrium over the tau region is
      shared by different ethnic groups indicating that haplotype structure in human is
      ancient. We discuss this observation in terms of the establishment of the
      haplotype structure and the possible impact of the tau haplotype on
      neurodegeneration in humans.

PMID- 15740842
TI  - Atomoxetine and nicotine enhance prepulse inhibition of acoustic startle in
      C57BL/6 mice.
AB  - Deficits in sensory-gating, often measured as deficits in prepulse inhibition of
      acoustic startle (PPI), are associated multiple with disorders including
      schizophrenia, attention deficit and hyperactivity disorder (ADHD), and
      withdrawal from nicotine. Drugs that can reverse deficits in PPI may serve as
      therapeutic agents for nicotine withdrawal, ADHD, and/or schizophrenia. The
      present study investigated the effects of acute atomoxetine, a norepinephrine
      reuptake inhibitor, nicotine, and mecamylamine, a nicotinic acetylcholinergic
      antagonist, on PPI and acoustic startle in C57BL/6 mice. Three doses of
      atomoxetine (0.2, 2.0, and 20 mg/kg) were administered prior to testing PPI and
      startle. The 0.2 and 2.0 mg/kg doses enhanced PPI and the 20 mg/kg dose enhanced
      startle. A second experiment investigated the effects of 2.0 mg/kg atomoxetine
      and 1.0mg/kg mecamylamine administered alone or together on PPI and startle. As
      before, atomoxetine enhanced PPI. Mecamylamine did not alter PPI and did not
      block the enhancement of PPI by atomoxetine. Neither drug altered startle. A
      third experiment investigated the effects of 2.0 mg/kg atomoxetine and 0.125
      mg/kg nicotine administered alone or together on PPI and startle. Both drugs
      enhanced PPI when administered alone. However, when co-administered, no
      enhancement of PPI was seen. Neither nicotine nor atomoxetine altered startle.
      The present results demonstrate that acute doses of nicotine and atomoxetine
      enhance PPI independent of effects on startle and that the enhancement of PPI by
      atomoxetine occurs independent of the nicotinic acetylcholinergic system. Thus,
      the newly available medication for ADHD, atomoxetine, could be a potential
      therapeutic agent for disorders associated with disrupted PPI such as withdrawal
      from nicotine.

PMID- 15740843
TI  - Processing of temporary syntactic ambiguity in Italian "who"-questions: a study
      with event-related potentials.
AB  - This study investigated the processing of direct Italian "who"-questions,
      containing a temporary ambiguity of the syntactic role (subject/object) of the
      initial pronoun. To this aim we measured event-related potentials (ERPs) evoked
      by the disambiguating verbal agreement word and by the following ones. Results
      showed two positive deflections, corresponding to a P300 and to a P600, only at
      the target verb of the object-first extraction, the condition which has been
      demonstrated to be less preferred by speakers. The functional meaning of this
      positive complex, similar to patterns already reported for German subject/object
      ambiguous relative clauses, was discussed with reference both to results obtained
      in other languages using similar sentences and to psycholinguistic parsing
      models.

PMID- 15740844
TI  - P2 receptor antagonist PPADS confers neuroprotection against glutamate/NMDA
      toxicity.
AB  - The present study investigated the role of pyridoxal phosphate-6-azophenyl-2',4'
      disulfonic acid tetrasodium salt (PPADS), a P2 receptor antagonist, in protecting
      mouse cerebellar granule neurons (CGNs) against glutamate/NMDA-induced neuronal
      death. Neurotoxicity caused by 50 microM glutamate or 200 microM NMDA was
      significantly reduced in CGNs treated with PPADS. Such neuroprotection was in a
      time- and dose-dependent manner. The possibility that PPADS may block
      glutamate/NMDA-mediated intracellular Ca2+ influx to CGNs was investigated using
      temperature-controlled platereader measurements of fluorescence intensity of CGNs
      loaded with Ca2+-sensitive fluorescent dye Fluo-4AM. Interestingly, the rapid
      increase of calcium influx following glutamate/NMDA treatment was not
      significantly affected by prior treatment with PPADS. In contrast, MK801, a
      specific NMDA receptor antagonist, completely blocked intracellular Ca2+ influx.
      Taken together, these data suggest that inhibition of the P2 receptor may
      directly modulate NMDA receptor-mediated neurotoxicity through a Ca2+-independent
      mechanism.

PMID- 15740845
TI  - Anxiolytic effects of intra-amygdaloid injection of the D1 antagonist SCH23390 in
      the rat.
AB  - The intercalated islands are intra-amigdaloid clusters of D1 receptor rich
      GABAergic neurons, which control impulse traffic between the basolateral complex
      and the central nucleus of the amygdala. As dopaminergic transmission within the
      amygdala may play a role in anxiety, the effect of the D1 antagonist SCH23390
      microinjected mainly close to the rostral intercalated islands in rats was
      studied, using the White and Black Box test. SCH23390 reduced anxiety by an
      increase in the latency of the first entry into the black compartment and by an
      increase in the total time spent in the white compartment of the White and Black
      Box test, while there was no significant modification of locomotion. It is
      suggested that blockade of D1 receptors in the rostral intercalated islands may
      reduce anxiety through a reduction of GABA-mediated dishinibition of the central
      amygdaloid nucleus.

PMID- 15740846
TI  - Biological effects of pramipexole on dopaminergic neuron-associated genes:
      relevance to neuroprotection.
AB  - Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist.
      Experimental studies have provided evidence that PRX may exert neuroprotective
      effects on the nigro-striatal system. Recent studies have demonstrated a slower
      decline of DAT density in Parkinson's disease patients treated with PRX as
      measured by SPECT. The aim of this study is to determine whether PRX has direct
      biological effects on DAergic neuron-associated genes expression, including DAT,
      VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for
      various time periods and harvested to measure the mRNA and protein products of
      these genes. Treatment with PRX at 10 microM significantly increased DAT mRNA
      levels by 54-130% in 4-8 h, VMAT2 mRNA levels by 34% in 4 h, and Nurr1 mRNA
      levels by 31-39% in 2-4 h, which was the earliest induction among these three
      genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after
      PRX treatment, among which the increase of Nurr1 protein level was the highest at
      first 2 h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the
      increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA
      receptor antagonist, didn't show this effect. Our findings that PRX has
      biological regulatory effects on DAergic neuron-associated genes may explain both
      the slower decline of imaged DAT and the neuroprotective effect of PRX.
      Furthermore, our results suggest that the induction of Nurr1 gene expression by
      PRX may be mediated by D3 DA receptor.

PMID- 15740847
TI  - Sodium cyanate-induced opening of calcium-activated potassium currents in
      hippocampal neuron-derived H19-7 cells.
AB  - We investigated the chemical toxic agent sodium cyanate (NaOCN) on the large
      conductance calcium-activated potassium channels (BK(Ca)) on hippocampal neuron
      derived H19-7 cells. The whole-cell and cell-attach configuration of patch-clamp
      technique were applied to investigate the BK(Ca) currents in H19-7 cells in the
      presence of NaOCN (0.3 mM). NaOCN activated BK(Ca) channels on H19-7 cells. The
      single-channel conductance of BK(Ca) channels was 138+/-7pS. The presence of
      NaOCN (0.3 mM) caused an obvious increase in open probability of BK(Ca) channels.
      NaOCN did not exert effect on the slope of the activation curve and stimulated
      the activity of BK(Ca) channels in a voltage-dependent fashion in H19-7 cells.
      The presence of paxilline or EGTA significantly reduced the BK(Ca) amplitude, in
      comparison with the presence of NaOCN. These findings suggest that during NaOCN
      exposure, the activation of BK(Ca) channels in neurons could be one of the ionic
      mechanisms underlying the decreased neuronal excitability and neurological
      disorders.

PMID- 15740848
TI  - The perception of fearful and happy facial expression is modulated by anxiety: an
      event-related potential study.
AB  - Anxiety is supposed to interfere with cognitive and emotional processing and high
      level of trait-anxiety has been associated with an attentional bias for fearful
      faces, even in sub-clinical anxiety. On the basis of the Spielberger State and
      Trait Anxiety Inventory (STAI), twenty students were grouped as low vs. high
      anxious. Pictures from the Ekman and Friesen series were used in an event-related
      potentials study to investigate the neurophysiological correlates of the
      emotional processing of fear and happiness in sub-clinical anxiety. Subjects were
      confronted with a visual oddball design, in which they had to detect, as quickly
      as possible, deviant happy or fearful faces amongst a train of standard stimuli
      (neutral faces). Anxiety does not modify early perceptual (N100, P100, N170, VPP)
      or attentional (N2b) component, but later components are affected. Indeed, high
      anxious subjects are faster to detect deviant faces as suggested by earlier
      reaction times and P3b component. However, they show a reduced ability to process
      the emotional content of faces, this deficit being indexed by a decreased N300
      component. Indeed, N300 is supposed to be particularly sensitive to affective
      features of stimuli rather than to physical characteristics. We propose that the
      earlier P3b observed in high anxious subjects could be interpreted as a way to
      overcome the deficient emotional appraisal by a more salient conscious
      processing.

PMID- 15740850
TI  - The extracellular calcium-sensing receptor increases the number of calcium steps
      and action currents in pituitary melanotrope cells.
AB  - Secretion of alpha-melanophore-stimulating hormone (alpha-MSH) from the
      neuroendocrine melanotrope cells in the intermediate lobe of the pituitary gland
      of the clawed frog Xenopus laevis is regulated by various inhibitory, stimulatory
      and autocrine factors. The neuropeptide sauvagine stimulates alpha-MSH secretion
      by changing the pattern of intracellular Ca2+ oscillations and the electrical
      properties of the cell membrane. In the present study we investigated whether
      another secreto-stimulator, the extracellular Ca2+-sensing receptor (CaR), also
      affects the Ca2+ oscillatory pattern and electrical membrane properties. Using
      high-speed dynamic video-imaging we show that activation of the CaR with the
      specific agonist l-phenylalanine (l-Phe) changes the Ca2+ oscillatory pattern by
      increasing the number of Ca2+ steps, which are the "building blocks" of the
      oscillations. Moreover, using patch-clamp electrophysiology it is demonstrated
      that l-Phe affects membrane properties by increasing frequency and duration of
      action currents. Compared to sauvagine, the CaR has different effects on the
      action current parameters, suggesting that multiple mechanisms regulate the
      electrical properties of the melanotrope cell membrane and, thereby, the Ca2+
      oscillation-dependent level of alpha-MSH secretion.

PMID- 15740849
TI  - Changes in DNA binding pattern of transcription factor YY1 in neuronal
      degeneration.
AB  - Molecular events under the neuronal degeneration are widely studied but still not
      defined. Here we compared the effects of both excitotoxic and apoptotic insults
      on the DNA binding profile of multifunctional transcription factor YY1 protein in
      cultured cerebellar granule neurons. We report that L-glutamate-induced
      excitotoxic insult but not ionophore A23187 treatment caused the disappearance of
      the larger DNA binding complex of YY1 and a simultaneous appearance of the
      smaller YY1 complex in cerebellar granule neurons. MK-801 (NMDA receptor
      antagonist) as well as benzamide (PARP inhibitor), MDL 28170 (calpain inhibitor)
      and roscovitine (cyclin-dependent kinase inhibitor) inhibited the glutamate
      response to the YY1 complexes. Herbimycin, PD169316, wortmannin, JAK3 inhibitor,
      KN-93, H-7 and LY294002 were not effective. Apoptosis induced by okadaic acid but
      not that induced by etoposide or trichostatin A caused a similar excitotoxic
      reorganization in YY1 complexes. We suggest that despite the different cell death
      mechanisms, glutamate and okadaic acid activate signalling cascades that affect
      the formation of YY1 complexes and probably YY1-mediated gene regulation.

PMID- 15740851
TI  - Is brain dehydroepiandrosterone synthesis modulated by free radicals in mice?
AB  - Dehydroepiandrosterone (DHEA) is a neurosteroid synthesized de novo in the brain,
      in addition to the periphery, modulating some membrane, ion-gated channel
      neurotransmitter receptors. P450-17alpha-hydroxylase activity converting
      pregnenolone to DHEA, has not yet been identified in the brain of rodents.
      Studies in brain-derived primary cultures and cell lines, suggest a possible
      alternative pathway for DHEA synthesis involving oxygenated hydroxyperoxides. We
      investigated DHEA synthesis in the brains of castrated male mice before and after
      treatment with N-acetylcysteine amide (AD4) (a newly developed brain penetrating
      antioxidant). We found a significant increase in brain DHEA level 24 h after
      castration, which was totally blocked by AD4. This blockade of castration-induced
      increased brain DHEA synthesis, supports the assumption that this synthesis may
      also be affected by free radicals. This is the first in vivo study indicating the
      possible existence of an in-brain oxidative stress-related pathway leading to
      brain DHEA production.

PMID- 15740852
TI  - Alterations in opioid system of the rat brain after cat odor exposure.
AB  - The effect of cat odor exposure was studied on morphine-induced increase of
      exploratory behavior and on the expression of opioid genes in forebrain
      structures of male Wistar rats. Treatment with morphine (1 mg/kg) induced a
      significant increase in exploratory behavior in an unfamiliar environment in
      rats. Previous exposure of animals to cat odor completely abolished this
      stimulating action of mu-opioid receptor agonist on exploratory activity. Cat
      odor exposure induced a significant increase in the expression of pro-opio
      melanocortin (POMC) and mu-opioid receptor (MOR) genes in the brain structures
      related to anxiety and motivation. This study clearly demonstrates that cat odor
      exposure increases the activity of opioid system in rat forebrain structures.

PMID- 15740853
TI  - Comparison of a commercial ELISA with the modified agglutination test for
      detection of Toxoplasma infection in the domestic pig.
AB  - The modified agglutination test (MAT) and a commercially available enzyme-linked
      immunosorbent assay (ELISA) were compared for detection of antibodies to
      Toxoplasma gondii in naturally-infected market-aged pigs. Infected pigs were
      obtained from commercial slaughter facilities and from farms where infection had
      previously been detected. Infection was confirmed by bioassay in cats. For 70
      bioassay positive pigs, 60 were positive by MAT (85.7% sensitivity) and 62 were
      positive by ELISA (88.6% sensitivity). Of 204 bioassay negative samples 193 were
      negative by MAT (94.6% specificity) and 200 were negative by ELISA (98.0%
      specificity). Good correlation was seen between MAT and ELISA results. The
      results suggest that the ELISA may be a good tool for epidemiological studies of
      Toxoplasma infection on pig farms.

PMID- 15740854
TI  - Disseminated Acanthamoeba sp. infection in a dog.
AB  - Several species of free-living amoebae can cause encephalomyelitis in animals and
      humans. Disseminated acanthamoebiasis was diagnosed in pyogranulomatous lesions
      in brain, thyroid, pancreas, heart, lymph nodes, and kidney of a one-year-old
      dog. Acanthamoeba sp. was identified in canine tissues by conventional histology,
      by immunofluorescence, by cultivation of the parasite from the brain of the dog
      that had been stored at -70 degrees C for two months, and by PCR. The sequence
      obtained from the PCR product from the amoeba from the dog was compared to other
      sequences in the Acanthamoeba sp. ribosomal DNA database and was determined to be
      genotype T1, associated with other isolates of Acanthamoeba obtained from
      granulomatous amebic encephalitis infections in humans.

PMID- 15740856
TI  - IgG avidity pattern in cattle after ingestion of Neospora caninum oocysts.
AB  - The avidity (functional affinity) of specific antibodies are being used to
      estimate duration of bovine Neospora caninum infection. Here, we report for the
      first time the avidity pattern in cattle orally inoculated with N. caninum
      oocysts. In all, 16 pregnant cows and 7 calves were administered N. caninum
      oocysts. In the cows, the avidity increased during the early course of infection.
      In all but one, the avidity was < or = 35 during the first 6 weeks after
      infection and no cow had an avidity value >50 until week 9. The calves were
      sampled either week 6 (n = 3) or week 9 (n = 9) after infection, and by then had
      avidities between 2 and 17. The results are in agreement with results from
      previous investigations of naturally infected cattle, and calves that were
      experimentally infected with tachyzoites. They further validate the ability of
      the N. caninum iscom avidity ELISA to accurately assess the duration of
      infection.

PMID- 15740855
TI  - Prevalence of antibodies against Neospora caninum and Toxoplasma gondii in dogs
      and foxes in Austria.
AB  - Sera from 1770 dogs and 94 red foxes from Austria were examined for antibodies
      against Neospora caninum using the indirect immunofluorescent antibody test
      (IFAT). 3.6% of the dogs were seropositive with titres ranging from 1:50 to
      1:6400. Dogs from rural areas were significantly more often seropositive for N.
      caninum than those from the urban area of Vienna (5.3% versus 2.1%). There were
      no significant differences in sex or breed, but a slight increase in
      seropositivity with age was apparent, indicating postnatal infection. None of the
      foxes had antibodies against N. caninum. Additionally, sera from 242 dogs and 94
      foxes were examined for antibodies against Toxoplasma gondii using the IFAT.
      Thirty-five percent foxes and 26% of the dogs were positive; 1.7% of the dogs
      were positive for both parasites. This is the first report of the prevalence of
      N. caninum infections in dogs and foxes in Austria.

PMID- 15740857
TI  - A longitudinal epidemiological survey of bovine trypanosomosis and its vectors in
      the White Volta river basin of Northern Ghana.
AB  - A longitudinal epidemiological survey of bovine trypanosomosis and its vectors
      was carried out in the Volta river basin of Northern Ghana to determine the
      relationship between cattle management and the incidence of bovine
      trypanosomosis. Two groups of sentinel cattle under different systems of
      management, classified as "fully-sedentary" and "partially-sedentary" (depending
      on the type of management) were followed over a 1-year period starting from March
      2003 onwards. Cattle were screened at intervals of 3 months using the buffy coat
      technique (BCT). Buffy coat specimen from animals that were positive for the BCT
      and those that were negative, but with a packed cell volume (PCV) of less than
      21% were further tested using the polymerase chain reaction (PCR). Plasma from
      all animals were tested for antibody using the indirect antibody enzyme-linked
      immunosorbent assay (ELISA). Trypanosomosis challenge was determined in tandem
      with the epidemiological survey with watering sites of sentinel cattle being the
      foci of interest. The parasitological prevalence at the start of the survey was
      higher in the fully-sedentary group (9%) than in the partially-sedentary group
      (3%). In subsequent visits, however, the parasitological incidence was
      consistently higher in the partially-sedentary group than in the fully-sedentary
      group. The mean seroprevalence (ELISA) of both groups increased from 3% in March
      to 54% in December. Statistical analysis of the serological results using a
      random effect logistic regression, showed a significant difference in incidence
      of bovine trypanosomosis between the two groups. There was also a significant
      effect of time. The influence of cattle herding on host-vector-parasite interface
      and its consequence on the incidence of trypanosomosis are discussed.

PMID- 15740858
TI  - Prevalence and transmission of Neospora caninum within infected Swedish dairy
      herds.
AB  - In this long-term study, the changes in within-herd Neospora caninum
      seroprevalences and the relative importance of horizontal and vertical parasite
      transmission in Swedish dairy herds were investigated. The within-herd
      prevalences varied between 5.8% and 65.0% when the herds were first sampled.
      Comparing the prevalences of year 2000 with those found 2-3 years later, nine out
      of 14 investigated herds had a similar or lower within-herd prevalence while five
      herds had an increased portion of seropositive individuals. Three herds were free
      or almost free from infection at their last sampling. Changes in prevalence were
      not related to the level of prevalence that each herd had when first sampled.
      Antibody avidity measurements revealed that the majority of seropositive
      individuals in all herds were chronically infected. Dam-calf pair investigations
      and inspection of genealogic trees supplemented with antibody test results showed
      that vertical transmission was by far the dominant transmission route in all
      herds. Taken together, these results indicate that the prevalence of N. caninum
      infection in Swedish dairy cattle can be successfully reduced if actions to
      eliminate infection in a herd are combined with preventive measures to avoid re
      infection.

PMID- 15740859
TI  - Neospora caninum in pastured cattle: determination of climatic, environmental,
      farm management and individual animal risk factors using remote sensing and
      geographical information systems.
AB  - A cross-sectional serological survey was conducted on cattle pasturing in an area
      of the southern Italian Apennines to evaluate the seroprevalence to Neospora
      caninum, and to investigate the climatic, environmental, farm management, and
      individual animal factors that influence the distribution of this protozoan.
      Blood samples were collected from 864 pastured cattle raised on 81 farms. Serum
      samples were tested for antibodies to N. caninum using an ELISA assay
      (HerdCheck), IDEXX). A geographical information system (GIS) for the study area
      was constructed using the following remote sensing (RS) and landscape feature
      data: autumn-winter, spring and summer normalized difference vegetation index
      (NDVI), land cover, elevation, slope, aspect, mean rainfall and minimum, mean,
      and maximum temperature in spring, summer, autumn and winter. Data on each of
      these features were then extracted for "buffer zones" consisting of the area
      included in a circle of 3 km diameter centered on the 81 geo-referenced centroids
      of the main cattle pastures. Climatic and environmental data obtained from RS and
      GIS and individual animal characteristics and farm management data obtained from
      a questionnaire were analyzed in relation to N. caninum seropositivity and
      antibody titres both by linear and logistic regression models. Out of the 81
      farms sampled, 63 (77.8%) had at least one tested animal positive for N. caninum.
      Out of the 864 bovine sera samples, 266 (30.8%) were found to have antibodies to
      N. caninum. The results of the logistic regression model show that significantly
      high seroprevalence to N. caninum was found in heifers/steers and adults, in
      cattle raised on farms having a large number of dogs, and in cattle raised in
      buffer zones having high minimum temperatures in the spring, and a narrow
      extension of summer NDVI. In addition, positive linear correlations were found
      between N. caninum antibody titres and the number of dogs on farm, and the
      minimum temperature in spring. All the above determined risk factors for N.
      caninum seroprevalence indicate that horizontal infection resulting from the
      ingestion of oocysts shed by dogs is the most probable route of N. caninum
      infection in pastured cattle of the southern Italian Apennines.

PMID- 15740860
TI  - Neospora abortions in dairy cattle: diagnosis, mode of transmission and control.
AB  - AIM: To determine the contribution of Neospora caninum to abortions on a dairy
      farm in NSW (Australia), determine the mode of transmission and develop and trial
      a control option for infection. METHODS: Two whole herd bleeds were conducted 12
      months apart and the association between serological status and abortion events
      were calculated for a number of bovine abortifacients. Family trees were
      constructed for N. caninum seropositive cattle in the herd. Some N. caninum
      seropositive cows were culled from the herd and no female offspring was retained
      from seropositive cows. RESULTS: At the first whole-herd bleed in December 2002 a
      seroprevalence of 10.2% for N. caninum infection was detected. Cows with N.
      caninum infection were 13 times more likely to abort than uninfected ones.
      Seventy-five percent of seropositive animals in the herd were related, suggesting
      a high degree of congenital infection/transmission. Only 15% of infections were
      likely to be postnatally acquired. Selective culling of seropositive cows and not
      breeding from them reduced the number of seropositive animals. Only one newly
      sero-converted cow was detected at the second whole-herd bleed 12 months later.
      CONCLUSIONS: Seroepidemiological approaches were able to establish a high degree
      of association between N. caninum infection and low-level abortion in the dairy
      herd. Vertical transmission of infection was the predominant mode of infection
      and hence control efforts aimed at selectively culling seropositive animals from
      the herd were highly successful in reducing the level of infection.

PMID- 15740861
TI  - Clinical and serological follow-up in dogs with visceral leishmaniosis treated
      with allopurinol and sodium stibogluconate.
AB  - Seven dogs with parasitologically proven clinical visceral leishmaniosis
      (Leishmania infantum infection) were treated with a combination of allopurinol
      and sodium stibogluconate. The dogs received first orally 15 mg/kg of allopurinol
      every 12 h until the clinical signs improved, in the following 1 month period
      allopurinol at same dose and subcutaneously 30 mg/kg of sodium stibogluconate
      combination were given daily and at the end of the combined treatment,
      allopurinol was continued alone at the same dose till the end of 8 months. During
      the treatment period, dogs were supported by additional proteins, vitamins, and
      minerals. A long acting insecticide (collar or drop) was also used in order to
      prevent further parasite transmission. Follow-up was maintained by clinical,
      clinicopathological evaluation, and parasitological examination of lymph node,
      serology using the indirect immunofluorescent antibody test (IFAT). Before
      treatment commenced, the most important clinical signs were exfoliative
      dermatitis, ulcerations, peripheral lymhadenopathy, pale mucous membranes, weight
      loss, and ocular lesions. Clinicopathological findings included commonly anaemia,
      hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. Before the treatment,
      amastigotes were seen in six of the seven dogs by examination of lymph node
      aspiration, and IFAT-titers were positive in all dogs. At the end of 8 months
      treatment, remission of clinical signs, restoration to normal of
      clinicopathological abnormalities were noticed. Lymph node aspiration was
      performed on three out of the seven dogs at the end of the treatment because of
      the very small sizes of the lymph nodes, and no amastigotes were observed.
      Although the mean IFAT-titer of the dogs were significantly (P < 0.001) lower
      compared with pretreatment, IFAT-titers of dogs were still positive. No relapses
      occurred during treatment period and a 6-24-month duration after the end of
      therapy. Based on the above results, long-term use of allopurinol combined with
      sodium stibogluconate together with support treatment concluded to have enough
      therapeutic efficacies in the treatment of dogs with visceral leishmaniosis.
      Observations of the cases for possible relapses were still going on and
      insecticide application was carefully carrying on in order preventing a possible
      re-infection.

PMID- 15740862
TI  - Influence of the route of administration on efficacy and tissue distribution of
      ivermectin in goat.
AB  - The tissue concentration and efficacy of ivermectin after per os and subcutaneous
      administration were compared in goats experimentally infected with
      Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected
      goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with
      ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and
      small intestine worm counts were determined. Ivermectin concentration was
      measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and
      adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin
      against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous
      and oral administration, respectively. Ivermectin concentration declined with
      time and only residual concentration was measured at 17 days post-treatment in
      plasma and gastrointestinal tract. Ivermectin concentration was higher after
      subcutaneous compared to per os injection in most of the tissue examined. In
      skin, hair and subcutaneous adipose tissue ivermectin persisted at significant
      concentrations 17 days post-treatment for both routes of administration. In our
      experimental conditions, ivermectin provides similar efficacy against T.
      colubriformis after subcutaneous or per os administration in goat. However, the
      lower ivermectin levels in tissues after per os administration suggest that the
      lasting of efficacy may be shortened after per os compared to subcutaneous
      administration especially in animals with poor body condition in pasture where re
      infection occurs quickly after anthelmintic treatment.

PMID- 15740863
TI  - Larval development assay for detection of anthelmintic resistance in
      cyathostomins of Swedish horses.
AB  - The aim of this study was to investigate the suitability of a larval development
      assay (LDA) for the determination of anthelmintic resistance in cyathostomin
      nematode populations of the horse. In addition, comparison of results between
      geographic regions, types of horse establishment, and the use of anthelmintics in
      Sweden, was established. Seventy horse herds from different parts of Sweden were
      sampled, and strongyle eggs from the faeces of 54 of those were investigated by
      an LDA (DrenchRite). The following anthelmintics were tested: thiabendazole
      (TBZ), levamisole (LEV), ivermectin monosaccharide (IVM-MS), ivermectin aglycone
      (IVM-AG) and pyrantel (PYR). The LC50 values for TBZ and LEV were generally lower
      than those previously reported in other LDA studies on horse nematodes. This
      could be related to the infrequent use of these compounds for the past 20 years
      in Sweden. In this study, there was a great variation within and between assay
      plates that could not be explained. Still the LC50 values differed significantly
      between the regions for all anthelmintics, except for pyrantel. The highest LC50s
      were observed in parasite populations from the south of Sweden. There were no
      significant differences between riding schools and studs. Limitations of this
      technique exist, namely the lack of established cut-off values for susceptible
      and resistant populations and interpretation problems related to multi-species
      infections. Although there are advantages with LDA such as the possibility of
      testing several compounds simultaneously without interference with the deworming
      programmes on the farms, we conclude that LDA currently is not a reliable
      alternative to the faecal egg count reduction test (FECRT).

PMID- 15740864
TI  - Haemonchus contortus egg excretion and female length reduction in sheep
      previously infected with Oestrus ovis (Diptera: Oestridae) larvae.
AB  - Mixed parasitic infection of animals is a common phenomenon in nature. The
      existence of one species often positively or negatively influences the survival
      of the other. Our experimental study was started with the objectives to
      demonstrate the interaction of Haemonchus contortus and Oestrus ovis in relation
      to cellular and humoral immune responses in sheep. Twenty-two sheep of
      Tarasconnais breed (France) were divided into four groups (O, OH, H and C) of
      five or six animals. Group O and OH received 5 weekly consecutive inoculations
      with O. ovis L1 larvae (total = 82 L1) in the first phase of the experiment
      between days 0 and 28. On the second phase, groups OH and H received 5000 L3 of
      H. contortus on day 48 while group C served as our control throughout the
      experimental period. Parasitological, haematological, serological and
      histopathological examinations were made according to standard procedures and all
      animals were slaughtered at day 95. There was no significant variation in the
      number and degree of development of O. ovis larvae between the two infected
      groups. Furthermore, in tissues examined in the upper respiratory tract (nasal
      septum, turbinate, ethmoide and sinus), group O and OH has responded similarly on
      the basis of cellular inflammatory responses (blood and tissue eosinophils, mast
      cells and globule leucocytes (GL)) and serum antibody responses against the nasal
      bots. This may indicate that the presence of H. contortus in the abomasa of group
      OH had no marked influence over the development of O. ovis larvae in the upper
      respiratory tract. On the other hand, we have observed a significantly lower H.
      contortus female worm length, fecal egg count (FEC) and in utero egg count in
      animals harbouring the nasal bot (OH) than in the mono-infected group (H). This
      was significantly associated with higher blood eosinophilia, higher packed cell
      volume (PCV) and increased number of tissue eosinophils and globule leucocytes.
      We conclude that, the establishment of O. ovis larvae in the upper respiratory
      tract has initiated higher inflammatory cellular activity in group OH there by
      influencing the development and fecundity of H. contortus in the abomasum.

PMID- 15740865
TI  - Multiple anthelmintic resistance in Haemonchus contortus isolated from South
      African Boer goats in Switzerland.
AB  - A suspected case of multiple anthelmintic resistance on a farm in the canton of
      Zurich, Switzerland, into which South African Boer goats had previously been
      imported, was confirmed in a controlled test. Twenty sheep were allocated into
      one control group and three treatment groups to determine the efficacy of
      mebendazole, ivermectin and moxidectin applying the faecal egg count reduction
      test (FECRT). The sheep were slaughtered 1 week later and post-mortem worm counts
      were performed. Benzimidazole and ivermectin resistance were found in Haemonchus
      contortus with an efficacy of 55 and 61%, respectively. Moxidectin appeared to be
      effective when the data was analysed according to the recommended analytical
      techniques with an efficacy of 96%. This is the first description of resistance
      of gastrointestinal nematodes to one of the macrocyclic lactones in small
      ruminants in Switzerland. The results are discussed in relation to the importance
      of controlling livestock before importation.

PMID- 15740866
TI  - Detection of anthelmintic resistance: a comparison of mathematical techniques.
AB  - Anthelmintic resistance has become an increasing problem particularly to
      gastrointestinal tract nematodes and appropriate methods are required to detect
      this phenomenon so the correct action can be taken. This paper compares a number
      of mathematical techniques that are used to analyse data. The negative binomial
      distribution is a mathematical distribution used to model aggregated data and
      hence is suitable to model the intensity of parasite burden and the magnitude of
      the faecal egg counts. Maximum likelihood techniques are utilised to exploit this
      mathematical distribution to analyse the magnitude of the faecal egg count
      reduction and decline in the worm burden in response to anthelmintic treatment.
      Data from experimental groups of sheep described in the accompanying paper are
      used. In addition, simulated data sets of faecal egg counts were created using a
      random number generator following appropriate negative binomial distributions.
      The results demonstrate this statistical model can detect evidence of
      anthelmintic resistance with a faecal egg reduction test that otherwise might
      require a slaughter trial to demonstrate. In addition, the simulated data sets
      confirm that there is a significant probability of failure to detect low
      anthelmintic efficacy with commonly used mathematical techniques. Consequently,
      the use of maximum likelihood mathematical techniques with a negative binomial
      statistical model would aid in the early detection of anthelmintic resistance
      using faecal egg count reductions and result in a lower probability of
      inappropriately assigning an anthelmintic as effective.

PMID- 15740867
TI  - Protection studies with a globin-enriched protein fraction of Ostertagia
      ostertagi.
AB  - The protective capacity of an adult stage Ostertagia ostertagi globin antigen was
      tested in four vaccination experiments in cattle. In a preliminary experiment,
      calves were vaccinated three times intraperitoneally with 250 microg globin in
      Freund's adjuvant and challenged with a trickled infection of 25,000 infective
      larvae. In three subsequent field studies, calves were vaccinated twice or three
      times intramuscularly with 80-100 microg globin in Quil A and challenged with a
      natural gastrointestinal nematode infection on pasture. Higher globin-specific
      antibody levels were detected in the vaccinated calves than in the control
      animals in all vaccine trials. In the preliminary experiment, geometric mean
      cumulative egg counts in the globin group were reduced by 52% and total worm
      burdens were reduced by 28%, compared to the controls. In the first field trial
      cumulative faecal egg counts were reduced by 63% in the vaccinated calves.
      However, the reduction in faecal egg output in these two experiments was not
      statistically significant and no reduction in faecal egg counts was observed in
      the vaccinated animals in the two last field trials. In conclusion, vaccination
      of calves with O. ostertagi globin resulted in highly variable protection levels
      after challenge infection.

PMID- 15740868
TI  - Local cytokine responses in Dictyocaulus viviparus infection.
AB  - The high degree of immunity induced by the bovine lungworm, Dictyocaulus
      viviparus, makes it an ideal model in which to study nematode-induced protective
      immune responses. Here, cytokine responses were measured over the course of an
      experimental infection of D. viviparus. Local cytokine messenger RNA (mRNA)
      transcripts were measured in lung parenchyma, tracheal rings and draining lymph
      nodes using semi-quantitative reverse transcriptase-polymerase chain reaction.
      Responses were measured in animals necropsied at 15, 22 and 43 days post
      infection (DPI). The responses elicited at these time points were compared with
      cytokine levels observed in uninfected animals. Interleukin (IL)-4, IL-5, IL-10,
      IL-12p35, IL-13 and interferon gamma (IFNgamma) mRNA levels were measured in
      duplicate at each site. By 42 DPI, very few parasites were recovered, either from
      faeces or lungs. Transcripts of all cytokines increased in the lung parenchyma,
      tracheal rings and caudal mesenteric lymph nodes by 15 DPI. The response was
      rapid and peaked during the time of larval migration through the lungs. By 42
      DPI, expression levels of most cytokines were reduced to levels similar to, or
      below, base line values measured in uninfected animals. Highest levels of IL-10,
      IL-12p35, IL-13 and IFNgamma transcript were measured in the bronchial lymph
      nodes of uninfected animals. IgG1 levels were negatively correlated with
      expression levels of all cytokines. The results demonstrate that a mixed cytokine
      response occurs over the course of a primary infection during which the parasites
      were eliminated by day 43 DPI. These results agree with those obtained for other
      helminths in cattle and challenge the hypothesis that polarised Th2 responses are
      essential for protection against nematodes in this species. These observations
      are important in the development of recombinant vaccines, particularly when
      considering adjuvant choice.

PMID- 15740869
TI  - A study of the acaricidal properties of an essential oil extracted from the
      leaves of Ageratum houstonianum.
AB  - Study on acaricide property of foam soap containing essential oil of Ageratum
      houstonianum leaves was tested on Rhipicephalus lunulatus. Four doses of the oil
      (0.00, 0.02, 0.025 and 0.03 microl/g) with four replications for each dose were
      used in vitro. Each replication consisted of 10 ticks in a Petri dish with filter
      paper impregnated uniformly with the foam soap on the bottom. The same four doses
      in three replications were used in vivo. Each replication was made up of 10
      naturally ticks infested goats. Results of this study indicate that foam soap
      containing essential oil of A. houstonianum leaves is toxic to R. lunulatus. The
      in vitro mortality rate was observed to vary from 0 to 50% on day 8 after
      treatment with the controls as compared to 95% with the lowest dose (0.02
      microl/g) on day 8 and 100% with the highest dose (0.03 microl/g) on day 3.
      Meanwhile, the in vivo mortality rate was observed to be 23.4% with the control
      on day 8 after treatment whereas the highest dose killed 95.1% of the ticks by
      this day. The LD50 of the foam soap containing essential oil of this plant was
      0.0259 and 0.0173 microl/g on day 2 after treatment, in the laboratory and on the
      farm, respectively. This indicates a potentially high efficiency of this
      medicated soap on this parasite.

PMID- 15740870
TI  - Lack of infectivity of a Brazilian Anaplasma marginale isolate for Boophilus
      microplus ticks.
AB  - Previous studies have shown that one Brazilian Anaplasma marginale isolate
      presents an inclusion appendage (tail), while other isolates do not present such
      inclusion. Studies on tick transmission have been carried out with tailless
      isolates but little is known about transmission of tailed isolates by Boophilus
      microplus. Two splenectomized calves were experimentally inoculated with the
      tailed A. marginale isolate. During ascending rickettsemia, B. microplus larvae,
      free from hemoparasites, were fed on the calves and the resulting nymphs, adult
      males and engorged females were examined by optic and electronic microscopy. No
      A. marginale colonies were observed in the gut cells of engorged females and the
      larvae originated from them did not transmit A. marginale to susceptible calves.
      In addition, no colonies of A. marginale were seen in the gut cells or in
      salivary glands of adult males and nymphs. These results suggest that B.
      microplus is not the biological vector for this tailed isolate.

PMID- 15740871
TI  - Survey on giardiosis in shelter dog populations.
AB  - Faecal samples from 183 dogs living in three different shelters in the Rome
      metropolitan area were randomly collected and examined for the prevalence of
      giardiosis. Giardia infections were detected by a commercially available ELISA
      test (ProspecT Giardia Microplate Assay). Overall prevalence was 55.2%.
      Prevalence rates in single shelters were 74.3, 35.5, and 20.9%, respectively.
      Using multivariate analysis, no association was found between Giardia-positivity
      and shelter or sex, breed, or diarrhoea. Giardia-positive dogs were more likely
      to be younger than 5-year-old (odds ratio [OR] = 2.87; 95% confidence interval
      [95% CI]: 1.07-7.77; p = 0.038), living together (OR = 2.58; 95% CI: 1.12-5.93; p
      = 0.026), and fed commercial wet food, both alone and combined with dry food (OR
      = 5.67; 95% CI: 1.59-20.24; p = 0.008). Correlation between Giardia infection and
      type of food has not been previously reported in dogs. Possible use of the ELISA
      test for detection of Giardia infection in dogs and zoonotic implications are
      discussed.

PMID- 15740872
TI  - Effect of ivermectin on feeding by Haemonchus contortus in vivo.
AB  - While several in vitro studies have shown that the anthelmintic ivermectin
      inhibits feeding by parasites, the relevance of this putative site of action in
      vivo has not been demonstrated. For this study, techniques to measure feeding by
      Haemonchus contortus in vivo relied on the blood feeding characteristics of the
      worm, and utilised tritiated inulin administered to sheep intravenously and
      subsequently measured in worms recovered from abomasa. Nematodes recovered from
      sheep treated with ivermectin 4 h prior to the [3H]inulin administration showed
      equivalent feeding levels (over a 1 h period) to those recovered from sheep not
      treated with ivermectin. In addition, there was no difference in the
      radioactivity in nematodes of an ivermectin-susceptible and an ivermectin
      resistant isolate recovered from individual sheep with concurrent infections
      after a dose with ivermectin. Ivermectin, therefore, had no effect on feeding by
      H. contortus in vivo under these experimental conditions. The results are
      discussed in relation to the dynamics of the expulsion of H. contortus from sheep
      following ivermectin treatment.

PMID- 15740873
TI  - Spatial distribution of Dermacentor reticulatus and Ixodes ricinus in Hungary:
      evidence for change?
AB  - A survey was conducted to investigate the spatial distribution of Ixodes ricinus
      and Dermacentor reticulatus in Hungary and to compare these data with the results
      of a previous large-scale survey. In the survey conducted in the 1950s, D.
      reticulatus adults were detected in two isolated areas of two counties, and the
      presence of these ticks in the collection was explained by accidental
      introduction. In the present survey, D. reticulatus became the second most common
      species occurring in all 16 counties involved in the monitoring and showed high
      prevalence. The change in the spatial distribution of this tick species, the
      increase of incidence of Babesia canis infection in Hungary, and the increasing
      number of canine babesiosis case reports from other Central and Central Eastern
      European countries since the 1970s suggest an expansion of the geographic range
      of D. reticulatus and intensification of the transmission rate of B. canis and
      probably other D. reticulatus-borne diseases (e.g. tularemia and tick-borne
      lymphadenopathy) in the region. The spatial distribution of I. ricinus was
      roughly in line with the results of the earlier survey. I. ricinus was the most
      common tick species being present in all 16 counties with the highest prevalence.
      Nevertheless, the comparison of the data of the previous and current survey
      cannot be used for fine-scale analysis; thus, it cannot be dismissed that the
      spatial distribution of I. ricinus also changed during the past decades. The
      spatial distribution patterns of tick-borne encephalitis in Hungary and other
      Central Eastern European countries may indicate such a change.

PMID- 15740874
TI  - Hypoderma sinense: a debated issue.

PMID- 15740875
TI  - Neurophysiological studies of Heteropteris glabra Hok. & Arn. (Malpighiaceae) in
      DBA/2J mice.
AB  - Fruits of Heteropterys glabra (Malpighiaceae) are used in South-American folk
      medicine as a sedative and anxiolytic agent. In present research, we studied
      neurophysiological effects of the plant. Ethanolic extract was assayed in DBA/2J
      mice in order to evaluate the sleep wakefulness cycle, electroencephalogram (EEG)
      and visual evoked potentials (VEP). The results of our experiments indicated that
      the EtOH extract of the plant induced a reduction of motor activity and
      alterations of EEG and VEP parameters, supporting the possibility that the plant
      acts as an anxiolytic/sedative agent, thus, confirming its usual assumption and
      the traditional use.

PMID- 15740877
TI  - Informant consensus factor and antibacterial activity of the medicinal plants
      used by the people of San Rafael Coxcatlan, Puebla, Mexico.
AB  - Using ethnobotanical techniques, the medicinal flora used by the inhabitants of
      San Rafael Coxcatlan, Puebla was determined. During the field work, two types of
      interviews were applied (free listing and semi-structured) to 60 informants, who
      supplied consistent information concerning the use of 46 species of medicinal
      plants. Further analysis showed 13 categories of different medicinal use. An
      informant consensus factor was calculated and 16 species were selected due to
      their utilization in the treatment of diseases of possible bacterial origin. Of
      these 16 plants, sequential extractions were made with hexane, ethyl acetate and
      methanol. The obtained extracts were used to assess their antibacterial activity
      against 14 bacterial strains; 75% of the plants presented antibacterial activity.
      The medicinal species Jatropha neopauciflora Pax (Euphorbiaceae) and Juliania
      adstringens (Schldl.) Schldl. (Julianiaceae) were those that showed the biggest
      activity. Moreover, these species also had the highest informant consensus factor
      values.

PMID- 15740876
TI  - Screening of some medicinal plants of Ethiopia for their anti-microbial
      properties and chemical profiles.
AB  - In the indigenous health care delivery system of Ethiopia, numerous plant species
      are used to treat diseases of infectious origin. Regardless of the number of
      species, if any of such claims could be verified scientifically, the potential
      significance for the improvement of the health care services would be
      substantial. The objective of this study was, therefore, to determine the
      presence of anti-microbial activity in the crude extracts of some of the commonly
      used medicinal plants as well as to identify the class of compounds in the plants
      that were subjected to such screening. Thus, the crude methanol, petroleum ether
      and aqueous extracts of 67 plant species were subjected to preliminary screening
      against 10 strains of bacterial species and 6 fungal strains using the agar
      dilution method. A sample concentration of 250-2000 microg/ml and 500-4000
      microg/ml were used for the bacterial and fungal pathogens, respectively. The
      results indicated that 44 different plant species exhibited activity against one
      or more of the bacteria while one species, viz., Albizzia gummifera showed
      activity against all the 10 bacteria at different gradient of dilution. Twenty
      three species inhibited or retarded growth of one or more organisms at dilution
      as low as 250 microg/ml. Extracts of same plants species were also tested against
      six different fungal pathogenic agents of which eight species showed growth
      inhibition against one or more of the organisms. Trichila emetica and Dovyalis
      abyssinica, which inhibited growth of four and five fungal strains at 100
      microg/ml concentration, respectively, were the most promising plants. Chemical
      screening conducted on the extracts of all the plants showed the presence of
      several secondary metabolites, mainly, polyphenols, alkaloids, tannins
      sterols/terpenes, saponins and glycosides. The plants containing more of these
      metabolites demonstrated stronger anti-microbial properties stressing the need
      for further investigations using fractionated extracts and purified chemical
      components.

PMID- 15740878
TI  - Effect of salvianic acid A on lipid peroxidation and membrane permeability in
      mitochondria.
AB  - Salvia miltorrhiza Bunge is a traditional Chinese medicine and has long been used
      for treating liver and heart diseases in China. Salvianic acid A is the main
      active component of Salvia miltorrhiza Bunge. In the present study, the ability
      of salvianic acid A in scavenging free radicals, inhibiting lipid peroxidation
      and mitochondrial membrane permeability transition, as well as respiration and
      protein thiol oxidation in rat liver mitochondria, was evaluated. The results
      show that salvianic acid A scavenges superoxide anions in a dose-dependent manner
      (IC50 52 microg/ml). Salvianic acid A could scavenge lipid free radicals and
      inhibit lipid peroxidation as effectively as Vitamin E. Salvianic acid A also
      inhibited the mitochondrial membrane permeability transition assessed as the
      extent of mitochondrial swelling. Salvianic acid A inhibited the oxidation of
      mitochondrial protein thiols involved in the mitochondrial membrane permeability
      transitions. We conclude that salvianic acid A is able to reduce lipid
      peroxidation in the mitochondrial membrane by scavenging free radicals, and
      inhibit mitochondrial membrane permeability transition by reducing protein thiol
      oxidation. These data indicated the pharmacological potential of salvianic acid A
      against pathological processes related to oxidative stress.

PMID- 15740879
TI  - Acute and chronic hypoglycemic effect of Ibervillea sonorae root extracts-II.
AB  - Ibervillea sonorae's root, or "wareque" (Cucurbitaceae), is widely used in
      Mexican traditional medicine for the control of diabetes mellitus. In the present
      study, the hypoglycemic effects produced by the acute and chronic administration
      of various extracts of Ibervillea sonorae were investigated. Both the traditional
      preparation (aqueous decoction) and the raw extract (juice) from the root
      resulted in significant reductions of glycemia in healthy mice after
      intraperitoneal administration at a dose of 600 mg/kg. Additionally, ground dried
      root was used to obtain a dichloromethane (DCM) extract and a methanol (MeOH)
      extract. The DCM extract induced a clear reduction of glycemia in healthy (P <
      0.05) and in alloxan-diabetic mice. The intraperitoneally administered DCM
      extract caused a severe hypoglycemia that produced lethality in all the treated
      animals when doses of 300 and 600 mg/kg body weight were used. Since the DCM
      extract showed a marked hypoglycemic activity, it was administered daily per os
      to alloxan diabetic rats, employing corn oil and tolbutamide as controls. After
      41 days of DCM extract administration at a dose of 300 mg/kg/day, diabetic rats
      showed improvement in glycemia, body weight, triglycerides, and GPT in comparison
      with the diabetic control group. Total cholesterol, GOT, and uric acid blood
      levels were not affected.

PMID- 15740880
TI  - Screening of some medicinal plants for anti-lipase activity.
AB  - In order to find new pancreatic lipase (triacylglycerol lipase, EC 3.1.1.3)
      inhibitors from natural sources, 75 medicinal plants belonging to different
      families were screened for their anti-lipase activity, using a radioactive
      method. On evaluating the results, methanolic extracts of three plants namely,
      Eriochloa villosa (Thunb.) Kunth, Orixa japonica Thunb. and Setaria italica (L.)
      Palib., exhibited strong in vitro anti-lipase activity (above 80%). These plants
      will be studied further to elucidate the structure and chemical properties of the
      active compound responsible for anti-lipase action.

PMID- 15740881
TI  - Effect of aqueous extract of the Desmodium gangeticum DC root in the severity of
      myocardial infarction.
AB  - The aqueous extract of Desmodium gangeticum (L) DC (Fabaceae) (DG) was studied in
      isoproterenol induced myocardial infarcted (MI) rats for the hypocholesterolemic
      and antioxidant effect. After inducing MI by isoproterenol (35 mg/kg b wt. i.p.),
      the aqueous extract of Desmodium gangeticum root at a dose of 3 ml/100 g b wt.
      was orally administered daily for a period of 30 days in six rats. On induction
      of MI, the activities of creatinine phosphokinase (CPK), lactate dehydrogenase
      (LDH), alkaline phosphatase (ALP) and serum glutamate oxaloacetate transaminase
      (SGOT) increased in myocardial tissue, hepatic tissue and serum. Pretreatment of
      DG to MI rats prevented the increase of these enzymes. The hypocholesterolemic
      effect of DG was assessed by the concentration of total cholesterol, low density
      lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and
      through the activities of 3-hydroxy 3-methyl glutaryl co-enzyme (HMG CoA)
      reductase and lecithin cholesterol acyl transferase (LCAT) in the myocardial
      tissue. The significant (P < 0.001) decrease in the concentration of
      thiobarbituric acid reactive substances (TBARS) and improved activities of
      glutathione reductase and catalase in the myocardial tissues of rats treated with
      DG suggest free radical scavenging activity of the extract.

PMID- 15740882
TI  - Phytochemical investigation and anti-inflammatory activity of aerial parts of
      Stachys byzanthina C. Koch.
AB  - From the aerial parts of Stachys byzanthina C. Koch., an acyclic diterpene ester,
      phytyl nonadecanoate, was isolated for the first time. In addition, two normal
      alkanes, one fatty acid and two sterols were also identified. Stuctures were
      established by conventional methods of analysis and confirmed by 1H, 13C NMR and
      mass spectral analysis. Anti-inflammatory effects of acetone and methanolic
      extracts of aerial parts of Stachys byzanthina C. Koch. were investigated in this
      study. For assessment of anti-inflammatory properties, two well-characterized
      inflammatory models, formalin test and carrageenan-induced paw edema were used.
      Intraperitoneal injections of either acetone or methanolic extract of Stachys
      byzanthina C. Koch. (50, 100 and 200 mg/kg), 30 min before formalin injection,
      had no effects against the first phase of the formalin-induced pain, but all
      three doses caused a significant blockade on the second phase (p < 0.01). The
      recording of the early phase started immediately after formalin injection and
      lasted for 10 min (0-10 min). The late response was recorded 20 min after
      formalin injection and lasted for 10 min (20-30 min). In the carrageenan-induced
      paw edema, both extracts revealed dose-related inhibitory effects on carrageenan
      induced rat paw edema over the dose range 50-200 mg/kg. The anti-inflammatory
      activities of these extracts were similar to a high dose of indomethacin (5
      mg/kg) in both carrageenan-induced paw edema and formalin-induced paw licking. In
      conclusion, the present data provide further evidence for an important role of
      extracts of Stachys byzanthina C. Koch. in the inhibition of pain and
      inflammatory processes.

PMID- 15740883
TI  - Protective effects of FBD--an experimental Chinese traditional medicinal formula
      on memory dysfunction in mice induced by cerebral ischemia-reperfusion.
AB  - With regards to the applications of three Chinese herbs poria, rhizoma
      atractylodis macrocephalae, and radix angelicae sinensis to vascular dementia
      (VD), the work was performed to assess the nootropic action and explore
      neuroprotective mechanisms of three herbs combinations (FBD) on mice injured by
      cerebral repetitive ischemia-reperfusion (IR). Aqueous extracts from FBD (115-460
      mg/kg) administered p.o. significantly improved cognitive function through
      elongating latency and reducing number of errors in step-through test. Aqueous
      extracts from FBD inhibited lipid peroxidation (LPO), elevated activity in (Na+)
      (K+)-ATPase and (Ca2+)-ATPase, reduced the production of nitric oxide (NO) in
      cortical tissue after IR, and artificial cerebrospinal fluid (ACSF) containing
      aqueous extracts from FBD (ACSF-FBD) (0.01-10 mg/L) protected also primary
      cortical cortex neurons (PCCN) from hypoxic and excitotoxic insult induced by
      sodium dithionite (1 mM) and monosodium glutamate (MSG) (0.5 mM) in vitro.
      Multiple anti-IR properties contributed probably FBD to ameliorate cognitive
      dysfunction shown in this murine model for VD.

PMID- 15740884
TI  - Effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract on plasma glucose
      and hepatic glycogen in streptozotocin-induced diabetic rats.
AB  - The present study investigates the hypoglycaemic effect of Syzygium cordatum
      (Hochst.) [Myrtaceae] leaf extract in non-diabetic and streptozotocin (STZ)
      induced diabetic rats. Oral glucose tolerance tests (OGGT) were conducted in non
      diabetic and STZ-diabetic rats using orally administered glucose (1.4 g 100 g(-1)
      body weight) followed by either the leaf extract (6 mg 100 g(-1) body weight) or
      subcutaneous (sc) injection of metformin (50 mg 100 g(-1)). Weekly plasma glucose
      and terminal hepatic glycogen concentrations were recorded in control STZ
      diabetic rats and diabetic rats orally treated with the leaf extract once every
      third day for 4 weeks. Administration of the leaf extract decreased plasma
      glucose from 7.7+/-0.9 mmol l(-1) to 3.7+/-0.6 mmol l(-1) (n = 6), and 21.1+/-2.2
      mmol l(-1) to 12.5+/-1.8 mmol l(-1) (n = 7) by 2 1/2 h in non-diabetic and STZ
      diabetic rats, respectively. OGTT data in metformin-treated rats were similar at
      the corresponding time in all groups, except for significant blood glucose
      reduction by the drug in non-diabetic rats between 1 and 1 1/2 h after treatment.
      Oral administration of the extract did not affect plasma glucose concentration in
      STZ-diabetic rats after 4 weeks, although it significantly increased hepatic
      glycogen content by comparison with untreated STZ-diabetic rats (28+/-5 mg 100 g(
      1) body weight, n = 7, versus 16+/-3 mg 100 g(-1) body weight, n = 6). We
      conclude that Syzygium cordatum leaf extract contains compounds that could be
      effective in mild diabetes mellitus or in cases of glucose tolerance impairment.
      The possible mechanism(s) involved in the short-term hypoglycaemic effect of the
      extract could not be established by the current study.

PMID- 15740885
TI  - Pharmacological studies of the aqueous extract of Sapindus trifoliatus on central
      nervous system: possible antimigraine mechanisms.
AB  - The aqueous extract of pericarp of fruits of Sapindus trifoliatus (ST) Linn.,
      family Sapindaceae was evaluated for its potential effects on central nervous
      system in mice. The extract at doses 20 and 100 mg/kg, i.p. significantly (p <
      0.001) reduced the spontaneous locomotor activity and at 100 mg/kg, increased the
      thiopental-induced sleeping time. In rota-rod motor co-ordination test, ST at 100
      mg/kg, i.p. significantly (p < 0.05-0.01) reduced the endurance time. Further ST
      exhibited no protection against maximal electroshock (MES)- and
      pentylenetetrazole (PTZ)-induced convulsions in mice. In receptor radioligand
      binding studies, ST exhibited affinity towards dopaminergic, alpha-adrenergic and
      muscarnic receptors. The findings suggest that, ST may possess principles with
      potential neuroleptic properties.

PMID- 15740886
TI  - Effect of mangiferin on hyperglycemia and atherogenicity in streptozotocin
      diabetic rats.
AB  - In the present study, the effect of mangiferin (a xanthone glucoside, isolated
      from the leaves of Mangifera indica) on the atherogenic potential of
      streptozotocin (STZ)-diabetes was investigated. In addition, the effect of
      mangiferin on oral glucose tolerance in glucose-loaded normal rats was also
      determined. The chronic intraperitoneal (i.p.) administration of mangiferin (10
      and 20 mg/kg) once daily (o.d.) for 28 days exhibited antidiabetic activity by
      significantly lowering fasting plasma glucose level at different time intervals
      in STZ-diabetic rats. Further, mangiferin (10 and 20 mg/kg, i.p.) showed
      significant antihyperlipidemic and antiatherogenic activities as evidenced by
      significant decrease in plasma total cholesterol, triglycerides, low-density
      lipoprotein cholesterol (LDL-C) levels coupled together with elevation of high
      density lipoprotein cholesterol (HDL-C) level and diminution of atherogenic index
      in diabetic rats. In addition, the chronic administration of mangiferin (10 and
      20 mg/kg, i.p.) for 14 days significantly as well as markedly improved oral
      glucose tolerance in glucose-loaded normal rats suggesting its potent
      antihyperglycemic activity. The accumulating evidences suggest that both
      pancreatic and extrapancreatic mechanisms might be involved in its antidiabetic
      or antihyperglycemic action. In conclusion, the present study demonstrates that
      mangiferin possesses significant antidiabetic, antihyperlipidemic and
      antiatherogenic properties thus suggesting its beneficial effect in the treatment
      of diabetes mellitus associated with hyperlipidemia and related cardiovascular
      complications.

PMID- 15740887
TI  - Effects of Ya-hom on blood pressure in rats.
AB  - The effects of Ya-hom, a traditional Thai herbal formulation, on blood pressure
      were evaluated to verify its use for fainting treatment. Ya-hom has several
      recipes, which are composed of different medicinal plants in varying ratio. We
      have selected the most popular commercial preparation to determine the effect on
      the blood pressure in rats. The water extract of Ya-hom at doses of 0.2, 0.4, 0.6
      and 0.8 g/kg initially transiently decreased pressure and over time, increased
      blood pressure. The duration of the Ya-hom effect on decreasing and increasing
      blood pressure was dose dependent. The time to maximal effect of Ya-hom on
      increasing blood pressure was also dose dependent. Phentolamine attenuated the
      blood pressure decreasing effect but did not affect the blood pressure increasing
      effect of Ya-hom. Ya-hom was previously shown to increase aortic ring
      contraction, which was partially inhibited by phentolamine, and increased atrial
      contraction. It is possible that phentolamine inhibits the effect of Ya-hom on
      vascular smooth muscle contraction resulting in a prominent positive inotropic
      effect. This may be the same reason that phentolamine does not influence the
      effect of Ya-hom on increasing blood pressure. The dominant effect of Ya-hom on
      increasing blood pressure supports the use of Ya-hom for the treatment of
      fainting.

PMID- 15740888
TI  - Anti-angiogenic effect of the seed extract of Benincasa hispida Cogniaux.
AB  - Benincasa hispida in Korea was used mainly diabetes and diuresis diseases. This
      study was carried out to evaluate anti-angiogenic effect of the seed extract of
      Benincasa hispida Cogniaux. Basic fibroblast growth factor (bFGF) is a potent
      angiogenic factor found in various tumors. In this study, we found that the seed
      extract of Benincasa hispida Cogniaux decreased bFGF-induced endothelial cell
      proliferation and tube formation in a dose-dependent manner. Besides, Benincasa
      hispida seed extract showed no cytotoxicity on HUVECs and normal fibroblast
      cells. Furthermore, the seed extract of Benincasa hispida showed a potent
      inhibitory effect on bFGF-induced angiogenesis in vivo. These results suggest
      that the seed extract of Benincasa hispida inhibits the proliferation of
      endothelial cells induced by bFGF, which may explain its anti-angiogenic
      properties.

PMID- 15740889
TI  - Kurarinone isolated from Sophora flavescens Ait inhibited MCP-1-induced
      chemotaxis.
AB  - The accumulation of circulating monocytes in the arterial wall is an early in
      atherosclerotic plaque formation. Monocyte chemoattractant protein-1 (MCP-1)
      promotes the migration of monocytes and would play a role in the development of
      atherosclerotic lesions. Searching for inhibitors of MCP-1-induced cell migration
      from natural sources, we isolated one active compound through active-guided
      fractionations from the MeOH extracts of Sophora flavescens Ait (Leguminosae). On
      the basis of spectral evidence, the structure of active compound was identified
      as kurarinone. It inhibited the migration of THP-1 cells induced by MCP-1 with
      IC50 value of 19.2 microg/mL. In addition, it inhibited the binding of MCP-1 to
      THP-1 cells and phosphorylation of p42/44 MARK.

PMID- 15740890
TI  - Free radical scavenging and hepatoprotective activity of jigrine against
      galactosamine induced hepatopathy in rats.
AB  - Jigrine a polypharmaceutical herbal hepatoprotective formulation containing
      aqueous extracts of 14 medicinal plants is used in Indian system of medicine
      (Unani). Jigrine was evaluated for its hepatoprotective activity against
      galactosamine induced hepatopathy in rats. Galactosamine induced hepatotoxicity
      resembles human viral hepatitis. Biochemical parameters like AST, ALT and urea in
      serum, TBARS and glutathione in liver and whole blood glutathione were estimated
      to assess liver function. DPPH-free radical scavenging activity of jigrine was
      also evaluated. Biochemical data exhibited significant hepatoprotective activity
      of jigrine against galactosamine. Silymarin used as reference standard also
      exhibited significant hepatoprotective activity against galactosamine. The
      biochemical observations were supplemented with histopathological examination of
      rat liver sections.

PMID- 15740891
TI  - Inhibition of Naja kaouthia venom activities by plant polyphenols.
AB  - Plant polyphenols from the aqueous extracts of Pentace burmanica, Pithecellobium
      dulce, Areca catechu and Quercus infectoria were tested for their inhibitory
      activities against Naja kaouthia (NK) venom by in vitro neutralization method.
      The first three extracts could completely inhibit the lethality of the venom at 4
      LD50 concentration and the venom necrotizing activity at the minimum necrotizing
      dose while also inhibited up to 90% of the acetylcholinesterase activity of NK
      venom at much lower tannin concentrations than that of Quercus infectoria. The
      ED50 of plant tannins in inhibiting NK venom activities varied according to
      condensed tannins and their content in the extracts. Molecular docking of the
      complexes between alpha-cobratoxin and either hydrolysable or condensed tannins
      at their lowest energetic conformations were proposed. The anti-venom activities
      of these plant polyphenols by selectively blocking the nicotinic acetylcholine
      receptor and non-selectively by precipitation of the venom proteins were
      suggested.

PMID- 15740892
TI  - In vitro screening of some Strychnos species for antiplasmodial activity.
AB  - The antiplasmodial activity of crude extracts of 19 species of Strychnos
      (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of
      Plasmodium falciparum. For each species, ethyl acetate (EtOAc) extracts were
      analysed and, for the most active species, methanolic (MeOH) extracts were also
      tested. Among them, Strychnos variabilis De Wild. seemed to be very promising
      (inhibitory concentration 50% (IC50) < 5 microg/ml) whereas two other species,
      Strychnos gossweileri Exell and Strychnos mellodora S. Moore, could be
      interesting (IC50 < 15 microg/ml) in further antimalarial studies.

PMID- 15740893
TI  - Antidepressant properties of some Hypericum canariense L. and Hypericum
      glandulosum Ait. extracts in the forced swimming test in mice.
AB  - It has been shown in a previous work that the methanol extract obtained from the
      aerial part in blossom of Hypericum canariense L. and Hypericum glandulosum Ait.
      was active in the tetrabenazine and forced swimming test. In the present study,
      the central nervous effect of the aqueous, butanol and chloroform fractions
      obtained from the methanol extracts of these Hypericum species was investigated
      in mice, particularly in animal models of depression. It was found that the
      immobility time in the forced swimming test was significantly reduced by the
      butanol and chloroform fraction of both species assayed, producing no effects or
      only a slight depression on spontaneous motor activity when assessed in a
      photocell activity meter. In this regard, the efficacy of the chloroform extract
      from Hypericum glandulosum Ait. (500 mg/kg p.o.) in the forced swimming test was
      comparable to that of the tricyclic antidepressant imipramine (50 mg/kg p.o.). In
      addition, the Hypericum glandulosum chloroform fraction was also effective in
      antagonizing the ptosis induced by tetrabenazine. Moreover, Hypericum canariense
      butanol fraction and Hypericum glandulosum chloroform fraction produced a slight
      but significant hypothermia. Taken together, these data demonstrate that the
      butanol and chloroform fractions from Hypericum canariense and Hypericum
      glandulosum possess antidepressant-like effects in mice, providing further
      support for the traditional use of these plants in the Canary Islands folk
      medicine against central nervous disorders.

PMID- 15740894
TI  - Anti-diarrhoeal and ulcer-protective effects of the aqueous root extract of
      Guiera senegalensis in rodents.
AB  - The anti-diarrhoeal and ulcer-protective properties of the aqueous root extract
      of Guiera senegalensis, a popular herbal traditional medicine in Nigeria were
      investigated in rats and mice. Acute toxicity studies were also carried out. The
      intestinal transit in mice was significantly (P < 0.05) reduced and gastric
      emptying delayed. One hundred and Two hundred milligrams per kilogram (p.o.) of
      the extract elicited a greater anti-motility activity than 0.1 mg/kg of atropine.
      The extract exhibited ulcer-protective properties against ethanol-induced
      ulceration in rats with maximal anti-ulcer activity recorded at 100 mg/kg. Guiera
      senegalensis also exerted significant anti-enteropooling effects causing a dose
      related inhibitory effect on castor oil-induced enteropooling in rats. A profound
      anti-diarrhoeal activity was observed when Guiera senegalensis was tested in
      diarrhoeic mice. The frequency of defaecation as well as the wetness of the
      faecal droppings was significantly reduced. Furthermore, the extract produced
      100% inhibition of castor oil-induced diarrhoea in mice. The oral LD50 values
      obtained were > 5000 mg/kg in both mice and rats. The results support the
      folkloric applications of Guiera senegalensis for the treatment of diarrhoea and
      ulcer in Nigerian herbal traditional medicine.

PMID- 15740895
TI  - The effects of acarbose and Rumex patientia L. on ultrastructural and biochemical
      changes of pancreatic B cells in streptozotocin-induced diabetic rats.
AB  - This study was performed to observe the effects of acarbose and Rumex patientia
      on morphological change of pancreatic B cells in streptozotocin (STZ)-induced
      diabetic (type 2) rats. Two-day-old Wistar albino rats were intraperitoneally
      injected with 100mg/kg of STZ or vehicle alone for control. Vehicle and STZ given
      rats were divided into six groups (1st, 2nd and the 3rd groups are control; the
      4th, 5th and 6th groups are STZ groups). The 1st and the 4th groups received
      water, the 2nd and the 5th groups received 40 mg acarbose/100 g feed, the 3rd and
      the 6th groups received 2% decoction of Rumex patientia grain. During
      experimentation period, blood glucose levels were checked periodically, and HbA1c
      level was measured from cardiac blood at the end of the experiment. Pancreas
      tissues were examined by electron microscope. Glucose and HbA1c levels increased
      by STZ were decreased by acarbose and Rumex patientia. Morphologically, we found
      a mitochondrial vacuolization and swelling as well as dilatation of the
      endoplasmic reticulum in the B cells of STZ-induced diabetic rats. Also, a
      decrease in the secretory granules of B cells was observed in the STZ-induced
      diabetic group. No pathological changes were observed in the STZ+acarbose group.
      In the STZ+Rumex patientia group, a weak swelling in the B cells was observed in
      the some of the mitochondria.

PMID- 15740896
TI  - Inhibition of lipopolysaccharide-inducible nitric oxide synthase expression by
      acteoside through blocking of AP-1 activation.
AB  - Acteoside is a phenylpropanoid glycoside with antioxidant and anti-inflammatory
      activities. We isolated acteoside from Buddlejae Flos, which has been used as a
      traditional medicine to treat conjunctive congestion and sepsis. The effect of
      acteoside on the expression of the inducible nitric oxide synthase (iNOS) gene
      was examined in the Raw264.7 macrophage cell line. An acteoside pretreatment
      significantly inhibited the release of NO in the cells treated with
      lipopolysaccharide (LPS). Western blot and RT-PCR analyses revealed that
      acteoside inhibited the LPS-induced levels of the iNOS protein and mRNA.
      Activation of the nuclear factor-kappaB (NF-kappaB) and the activator protein-1
      (AP-1) is the key step in the signaling pathways mediating iNOS induction. In
      this study, acteoside selectively suppressed AP-1 activation, which may be
      essential for iNOS induction in the LPS-treated macrophages. The inhibitory
      effect of AP-1 activation by acteoside may be associated with the anti
      inflammatory effects of Buddlejae Flos.

PMID- 15740897
TI  - Erythrodiol-3-acetate, pentacyclic triterpenoid from Styrax japonica, expressions
      of matrix metalloproteinase-1,2 in cultured human skin fibroblasts.
AB  - Although many studies have been performed to elucidate the molecular consequences
      of ultraviolet irradiation, little is known about the effect of natural products.
      Ultraviolet irradiation is widely considered to be an environmental stress. Here
      we investigated the effect of erythrodiol-3-acetate on the expressions of MMP-1,2
      in cultured human skin fibroblasts. Erythrodiol-3-acetate was isolated from the
      stems of Styrax japonica (Styracaceae). Erythrodiol-3-acetate reduced the
      expression of MMP-1 but not MMP-2, at the mRNA and protein levels in a dose
      dependent manner by ultraviolet irradiation. Taken together, our results suggest
      that erythrodiol-3-acetate an important role in the reduction of MMP-1 induction
      by ultraviolet irradiation.

PMID- 15740898
TI  - Spectroscopic study of fluorescent peptides for prenyl transferase assays.
AB  - A study of the prenyl transferase reactions was performed by fluorescence using
      rat brain cytosol fractions as an enzyme source. Four dansylated peptides
      corresponding to the C-terminal sequence of Ras isoforms were synthesised. The
      effects of different detergents on the farnesylation or geranylgeranylation of
      the four peptides were evaluated. Dose-dependent effects of dodecyl-maltoside, a
      non-ionic detergent, on the farnesyl transferase or geranylgeranyl transferase
      activities were observed with all peptide substrates. Additionally, the effect of
      temperature was investigated and these assays were applied to determine Michaelis
      Menten constants (K(m)) of the substrates: dansyl-GCVLS (1.8 microM), dansyl
      GCVVM (3.2 microM), dansyl-CVIM (3.4 microM) and dansyl-GCVLL (8.4 microM) and
      FPP (22.6 microM) for FTase activity. Using GGPP as co-substrate, GGTase activity
      was measured with K(m) values superior to 50 microM for all the three substrate
      dansyl-GCVLS, dansyl-GCVVM, or dansyl-CVIM, whereas values of 7.6 and 5.4 microM
      were calculated for the dansyl-GCVLL sequence and GGPP co-substrate,
      respectively. IC50 values of selective prenyl transferase inhibitors, B-581, FTI
      276 and GGTI 287 have been measured to 34, 0.8 and 18 nM, respectively, using
      dansyl-GCVLS as substrate (FTase inhibition). When dansyl-GCVLL is used as
      substrate (GGTase inhibition) the IC50 values are 5100, 75 and 5 nM for B-581,
      FTI 276 and GGTI 287, respectively. Then, this developed method allowed to
      evaluate the selectivity of all the three inhibitors tested.

PMID- 15740899
TI  - On-line capillary isoelectric focusing-mass spectrometry for quantitative
      analysis of peptides and proteins.
AB  - On-line capillary isoelectric focusing-mass spectrometry (cIEF-MS) was applied to
      determine concentrations of peptides and proteins using angiotensin II and human
      tetrasialo-transferrin as the model samples. The concentration of the carrier
      ampholyte was optimized for both resolution and ion intensity. cIEF-MS employing
      1% Pharmalyte 3-10 and a sheath liquid containing water/methanol/acetic acid
      (50/49/1) resolved angiotensin I and II (5 microM each, DeltapI=0.2) at an Rs
      value of 2.29. The determined concentration of angiotensin II (0.1-5 microM) well
      correlated (R=0.999) with that obtained by the conventional RP-HPLC method. The
      limit of detection was 0.22 microM, which was about 10 times lower than that by
      UV detection (2 microM). The repeatability and accuracy were <15 and <11%,
      respectively. cIEF-MS was also applied to determine human tetrasialo-transferrin
      concentration. The good linearity (R2=0.998) was also observed between the
      transferrin concentration (0.5-1.2 g/L) and peak area ratio (IS; beta
      lactoglobulin B) with acceptable accuracy (<1.9%) and repeatability (
      approximately 10% at 1g/L).

PMID- 15740900
TI  - Fast analysis of glycosaminoglycans by microchip electrophoresis with in situ
      fluorescent detection using ethidium bromide.
AB  - We analyzed some glycosaminoglycans and natural and artificial acidic
      polysaccharides using microchip electrophoresis in the buffer containing ethidium
      bromide, and found that they were successfully separated and detected within 150
      s with comparable sensitivity with that of conventional electrophoresis using
      cellulose acetate membrane. We applied the technique to the analysis of
      glycosaminoglycans in pharmaceutical preparations and also in cultured cancer
      cells. Rapidness and easy operation of the proposed technique are quite useful
      for routine analysis of glycosaminoglycans.

PMID- 15740901
TI  - Structural analyses of protoberberine alkaloids in medicine herbs by using ESI-FT
      ICR-MS and HPLC-ESI-MS(n).
AB  - The Electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry (ESI-FT-ICR-MS) using sustained off-resonance irradiation
      (SORI)/collision-induced dissociation (CID) method at high mass resolution has
      been first applied to investigate the characteristic fragment ions of four
      protoberberine alkaloids in medicine herbs. The ESI-FT-ICR SORI-CID experiment
      results demonstrate that the unambiguous elemental composition of fragment ions
      can be obtained at high mass resolution, then the logical fragmentation pathways
      of the protoberberine alkaloids has been proposed. The characteristic fragment
      ions of CID and MS(n) of protoberberine alkaloids have been discussed, which are
      specific and useful for the identification of some protoberberine alkaloid
      compounds. Then, the extracts of four kinds of medicine herbs have been analyzed
      by HPLC-ESI-MS(n). According to these characteristic fragmentation pathways, the
      retention time (t(R)) of HPLC and mass spectra of product ion, the structures of
      six kinds of protoberberine alkaloids have been identified. And, in the present
      paper, the selected ion monitoring (SIM) method has been used to separate and
      identify the alkaloid isomers.

PMID- 15740902
TI  - An HPLC method for quantitation of perillyl alcohol in a topical pharmaceutical
      cream formulation.
AB  - A reverse phase high performance liquid chromatographic method for quantitation
      of perillyl alcohol in a topical cream pharmaceutical formulation was developed.
      Previously reported methods for analyzing drugs in lipid formulations are
      relatively complex and time consuming, with extraction, purification and
      derivatization involved. Through a simple dilution of the cream formulation in
      isopropyl alcohol, the present assay method enables the direct injection of the
      samples, on an Alltima C18 5 mu, 150 mm x 2.1 mm, narrow bore column (Alltech
      Associates, Deerfield, IL). The method includes an isocratic run with
      acetonitrile-water (40:60, v/v) at 0.35 mL/min for 12 min, followed by a gradient
      wash with isopropyl alcohol for 20 min, to ensure that all formulation excipients
      are eluted. Ultraviolet detection was performed at 210 nm with a retention time
      for perillyl alcohol of 7 min. The high sensitivity assay utilizes a small (5
      microL) injection volume for the accurate and precise analysis of perillyl
      alcohol from a complex cream formulation.

PMID- 15740903
TI  - A validated chiral LC method for the determination of zolmitriptan and its
      potential impurities.
AB  - A new, accurate and reliable chiral HPLC method was developed for the
      determination of Zolmitriptan, (4S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]
      methyl]-2-oxazolidinone an antimigraine agent and its potential impurities namely
      (4R)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone [(R)
      enantiomer] and (4S)-4-(4-aminobenzyl)-2-oxazolidinone (Imp-1) in pharmaceutical
      formulations and in bulk drugs. HPLC separation was carried out by normal phase
      chromatography with a mobile phase composed of
      hexane:isopropanol:methanol:diethylamine in the ratio (75:10:15:0.1, v/v/v/v)
      pumped at a flow rate of 1.0 ml/min on a Chiralpak AD-H column. Zolmitriptan and
      its potential impurities were baseline resolved in the optimized method. The
      presence of diethylamine in the mobile phase has played a key role in achieving
      chromatographic resolution between the enantiomers and also in enhancing
      chromatographic efficiency. The developed method was also found to be selective
      under exposed conditions UV light and 60 degrees C. The developed method was
      completely validated and proved to be robust. The values of the limit of
      detection (LOD) and limit of quantification (LOQ) of (R)-enantiomer and Imp-1
      were 100, 250 ng/ml and 30, 1000 ng/ml, respectively, for 10 microl injection
      volume. The validated method yielded good results regarding selectivity,
      linearity, precision, accuracy and ruggedness. Zolmitriptan sample solution and
      mobile phase are found to be stable for at least 24 h. The proposed method was
      found to be suitable and accurate for the quantitative determination of
      Zolmitriptan and its impurities namely (R)-enantiomer and Imp-1 in bulk drugs and
      commercial formulations.

PMID- 15740904
TI  - A validated HPLC method for determining residues of a dual active ingredient anti
      malarial drug on manufacturing equipment surfaces.
AB  - Analytical method validation, determining the recovery rate from the equipment
      surface and the stability of a potential contaminant are important steps of a
      cleaning validation process. A rapid, sensitive and reproducible reversed-phase
      high-performance liquid chromatographic method was developed for the
      determination of pyrimethamine (PYR) and sulfadoxine (SUL) in cleaning validation
      swab samples. The active compounds can be selectively quantified in a sample
      matrix containing detergent and swab material as low as 0.12 microg/ml. The
      swabbing procedure used on stainless steel coupons was validated and the
      stability of PYR and SUL in the swab samples was assessed. The calculated limit
      of contamination values for PYR (4.99 microg/cm2) and SUL (19.14 microg/cm2) were
      not exceeded during four consecutive equipment cleaning trials. This confirms
      that the desired level of cleanliness is achieved with the current cleaning
      procedures, which are consequently validated.

PMID- 15740905
TI  - Simultaneous determination of five marker constituents in traditional Chinese
      medicinal preparation Le-Mai granule by high performance liquid chromatography.
AB  - An HPLC method for the simultaneous determination of five marker constituents was
      established for the quality control of traditional Chinese medicinal preparation
      Le-Mai granule. The marker constituents were danshensu, protocatechuic acid and
      protocatechualdehyde from Salviae miltiorrhizae bunge; paeoniflorin from Radix
      paeoniae rubra and ferulic acid from Rhizoma chuanxiong. Extracted samples were
      successfully separated on a Diamonsil C18 column (150 mm x 4.6 mm i.d., 5 microm)
      at 25 degrees C. The mobile phase was a mixture of methanol and 1.0% acetic acid
      employing gradient elution at a flow rate of 1.0 mL/min. Detection was
      accomplished with a diode-array detector and chromatograms were recorded at 230,
      262, 280 and 322 nm. The compounds were identified by comparing their retention
      times and UV spectra in the 200-400 nm range with authentic standards. Regression
      equations revealed good linear relationship (correlation coefficients: 0.9993
      0.9999) between the peak areas of the constituents and their concentrations. The
      average recoveries (n=3) were between 96.2 and 102.5%. The proposed method has
      been successfully applied to the simultaneous determination of the five marker
      constituents in three lots of Le-Mai granule.

PMID- 15740906
TI  - Determination of modafinil in plasma and urine by reversed phase high-performance
      liquid-chromatography.
AB  - Modafinil (Provigil) is a new wake-promoting drug that is being used for the
      management of excessive sleepiness in patients with narcolepsy. It has
      pharmacological properties similar to that of amphetamine, but without some of
      the side effects associated with amphetamine-like stimulants. Since modafinil has
      the potential to be abused, accurate drug-screening methods are needed for its
      analysis. In this study, we developed a high-performance liquid-chromatographic
      procedure (HPLC) for the quantitative analysis of modafinil in plasma and urine.
      (Phenylthio)acetic acid was used as an internal standard for the analysis of both
      plasma and urine. Modafinil was extracted from urine and plasma with ethyl
      acetate and ethyl acetate-acetic acid (100:1, v/v), respectively, and analyzed on
      a C18 reverse phase column with methanol-water-acetic acid (500:500:1, v/v) as
      the mobile phase. Recoveries from urine and plasma were 80.0 and 98.9%,
      respectively and the limit of quantitation was 0.1 microg/mL at 233 nm. Forty
      eight 2-h post-dose urine samples from sham controls and from individuals taking
      200 or 400 mg of modafinil were analyzed without knowledge of drug
      administration. All 16-placebo urine samples and all 32 2-h post-dose urine
      samples were correctly classified. The analytical procedure is accurate and
      reproducible and can be used for therapeutic drug monitoring, pharmacokinetic
      studies, and drug abuse screening.

PMID- 15740907
TI  - Simultaneous determination of cryptotanshinone, tanshinone I and tanshinone IIA
      in traditional Chinese medicinal preparations containing Radix salvia
      miltiorrhiza by HPLC.
AB  - A reversed-phase high performance liquid chromatographic method was established
      for the simultaneous determination of tanshinones in five kinds of traditional
      Chinese medicinal preparations (TCMPs) containing Radix salvia miltiorrhiza
      (Chinese herbal name: Danshen). Tanshinones including cryptotanshinone,
      tanshinone I and tanshinone IIA were successfully separated on a Diamonsil C18
      column (150 mm x 4.6 mm i.d., 5 microm). The mobile phase was a mixture of
      methanol, tetrahydrofuran, water and glacial acetic acid (20:35:44:1, v/v/v/v),
      employing isocratic elution at a flow rate of 1.0 mL/min. Detection was
      accomplished at 254 nm. The compounds were identified by comparing their
      retention times and UV spectra in the 200-400 nm range with authentic standards.
      Regression equations revealed good linear relationship between the peak areas of
      the constituents and their concentrations (correlation coefficients: 0.9998 for
      cryptotanshinone, 0.9999 for tanshinone I and 1.0000 for tanshinone IIA). The
      relative standard deviations (n=6) of retention time and peak area were less than
      0.25% and 1.00%, respectively. The recoveries were between 96.2% and 102.5%. The
      proposed method has been successfully applied to the simultaneous determination
      of the tanshinones in five kinds of Chinese herbal preparations containing
      Danshen within 20 min.

PMID- 15740908
TI  - HPLC and solubility study of the interaction between pindolol and cyclodextrins.
AB  - The complexation with beta-cyclodextrin (beta-CD) has been investigated using
      reversed-phase liquid chromatography. The compounds tested have been pindolol
      and, for comparison purposes, indole and 4-methoxyindole. The retention behaviour
      has been analysed on a Kromasil 100 C18 column and the mobile phase used was
      methanol-pH 6 phosphate buffer (15/85v/v) in which beta-CD was incorporated as a
      mobile phase additive. The decrease in the retention times with increasing
      concentrations of beta-CD enables the determination of the apparent stability
      constants of the complexes. In addition, the low solubility of pindolol, a weak
      base, in pH 12 aqueous solution has been improved by complexation with different
      cyclodextrins. The solubility enhancements with 1.4 x 10(-2) M beta-,
      hydroxypropyl-beta, and gamma-CD have been 1.9, 1.8 and 1.4-fold, respectively,
      with 2.4 x 10(-2) M methyl-beta-CD it was 2.8-fold whilst no effect was observed
      with alpha-CD. The stability constants of the complexes at pH 12 have been
      determined from the solubility isotherms.

PMID- 15740909
TI  - Sample preparation optimization for assay of active pharmaceutical ingredients in
      a transdermal drug delivery system using experimental designs.
AB  - A simple but very effective sample preparation method is discussed for a matrix
      or drug-in-adhesive type of transdermal drug delivery system (TDS). The method is
      a one-step extraction using a methanol/water solvent system. Because of the
      unique design and physical property of the delivery system, special
      considerations were taken in selection of sample solvent, sample container and
      extraction enhancement device. The main focus of the article is on method
      optimization using experimental designs. A Plackett-Burman design was used to
      screen multiple method factors including extraction solvent strength, extraction
      solvent volume, shaking speed of a reciprocating shaker, and shaking time. Later,
      two of the factors were studied in more details using a 4 x 5 general factorial
      design. From the experimental results, the so-called main effects plots and
      interaction plots were generated using a statistical software. The plots are
      helpful in choosing the method conditions.

PMID- 15740910
TI  - Development and validation of a high-performance liquid chromatography-mass
      spectrometry assay for methylxanthines and taurine in dietary supplements.
AB  - A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described
      for determination of caffeine, theobromine, theophylline, taurine in different
      dietary supplements. After addition of tryptophan as internal standard, both
      solid and liquid specimens were extracted with 4 ml of hexane/isopropanol (9:1).
      Chromatography was performed on a C18 reversed-phase column using
      water/methanol/acetic acid (75:20:5, v/v/v) as a mobile phase. Analytes were
      determined in LC-MS single ion monitoring mode with atmospheric pressure
      ionization-electrospray (ESI) interface. The method was validated in the range
      0.1-500 and 0.06-500 microg/ml or microg/g for taurine and caffeine,
      respectively; 0.06-100 microg/ml or microg/g for theobromine and theophylline.
      Mean recoveries ranged between 70.1 and 94.4% for different analytes. The
      quantification limits were 0.1 microg/ml or microg/g for taurine and 0.06
      microg/ml or microg/g for methylxanthines either in liquid samples or in solid
      samples. The method was applied to the analysis of various dietary supplements
      containing methylxanthines and taurine. Energetic drinks contained amounts of
      taurine in the range of hundreds to thousands microg/ml and ten times lower
      amounts of caffeine. Conversely, herbal powders, tablets and capsules mainly
      contained mg amounts of caffeine per gram of product with the other two
      methylxanthines in the range of ten to hundred microg/g.

PMID- 15740911
TI  - Infrared studies of the polymorphic states of the fenamates.
AB  - Infrared spectroscopy has been used to characterize the polymorphic purity as
      well as to study the thermal conversion of three of the more common fenamates
      between their different crystalline forms via measuring changes in the NH stretch
      region that occur between 3300 and 3350 wavenumbers. Shifts in band frequency for
      mefenamic acid result from differences in internal hydrogen bonding between the
      NH group and either the carbonyl or hydroxyl groups of the acid moiety. Due to
      out-of-plane rotations about the central N-C(ring2) bond additional polymorphic
      states have been suggested for flufenamic and tolfenamic acids. Rates of
      conversion are given for flufenamic, mefenamic, and tolfenamic acids at
      temperatures between 85 and 160 degrees C depending on the polymorphic transition
      for a particular analyte. Subsequently, these rates are used to calculate the
      activation energy for the observed polymorphic transition. Values of 71.6, 49.0,
      and 50.8 kcal/mol are obtained respectively for (1) the polymorph I to II
      transition of mefenamic acid, (2) the polymorph I to II transition of tolfenamic
      acid, and (3) the polymorph III to I transition of flufenamic acid.

PMID- 15740912
TI  - Simultaneous determination of ingredients in a cold medicine by cyclodextrin
      modified microemulsion electrokinetic chromatography.
AB  - Cyclodextrin-modified microemulsion electrokinetic chromatography (CD-MEEKC) was
      used to simultaneously determine 14 active ingredients (thiamine nitrate,
      anhydrous caffeine, acetaminophen, riboflavin, guaifenesin, pseudoephedrine
      hydrochloride, ascorbic acid, ethenzamide, DL-methylephedrine hydrochloride,
      dihydrocodeine phosphate, ibuprofen, noscapine, carbinoxamine maleate, and
      bromhexine hydrochloride) in a cold medicine. Separation of the ingredients was
      optimized by changing the SDS concentration and oil type and the addition of 2
      propanol and cyclodextrin (CD) to the separation solution. The separation
      selectivity was improved dramatically by changing CD type. All of the active
      ingredients and formulation excipients were successfully separated with the use
      of a separation solution consisting of 0.81% (w/w) pentane, 6.61% (w/w) 1
      butanol, 2% (w/w) 2-propanol, 4.47% (w/w) SDS, and 86.11% (w/w) 10 mM sodium
      tetraborate solution with 3 mM 2,6-di-O-methyl-beta-CD. The established method
      was then validated and demonstrated to be applicable to the determination of the
      active ingredients in a model cold medicine. No interference from the formulation
      excipients was observed. Good linearities were obtained with correlation
      coefficients above 0.999. Recovery and precision ranged from 99.1 to 100.7% and
      from 0.5 to 2.8% R.S.D., respectively. The detection limit for ingredients ranged
      from 0.6 to 4.2 microg ml(-1). Good agreement was obtained between the
      established method and the traditional HPLC method. These results suggest that CD
      MEEKC can be used for the determination of multiple ingredients in cold medicine.

PMID- 15740913
TI  - Determination of topiramate and its degradation product in liquid oral solutions
      by high performance liquid chromatography with a chemiluminescent nitrogen
      detector.
AB  - Topiramate is a sulfamate-substituted monosaccharide that is prescribed for the
      treatment of epilepsy. It has been a challenge to develop analytical methods for
      topiramate formulations because the compounds of interest do not have
      chromophores that are active above 190 nm and because of interference from
      excipients. This paper describes a simple, specific, precise, accurate, and
      sensitive method using a chemiluminescent nitrogen detector. The method has a
      validated linearity range of 32-4800 ng of topiramate and excellent precision
      (system repeatability). The limit of quantitation was determined to be 0.1% for
      the degradation product w/w versus topiramate. The method has been successfully
      used for probe stability studies in support of early phase formulation
      development.

PMID- 15740914
TI  - Simultaneous determination of active ingredients in Erigeron breviscapus (Vant.)
      Hand-Mazz. by capillary electrophoresis with electrochemical detection.
AB  - A high-performance capillary electrophoresis (CE) with electrochemical detection
      (ED) method was developed for the determination of the pharmacologically active
      ingredients in Erigeron breviscapus (Vant.) Hand-Mazz. and its extract
      phytopharmaceuticals in this work. Under the optimum conditions, nine analytes,
      baicalein, naringenin, scopoletin, kaempferol, apigenin, scutellarin, luteolin,
      caffeic acid and protocatechuic acid were separated within 24 min in a borax
      buffer (pH 8.7). Notably, excellent linearity was obtained over two orders of
      magnitude with detection limits (S/N=3) ranged from 1.0 x 10(-7) g/mL to 5.6 x
      10(-7) g/mL for all nine analytes. This method was successfully used in the
      analysis of E. breviscapus (Vant.) Hand-Mazz. and its phytopharmaceuticals with a
      relatively simple extraction procedure, and the assay results were satisfactory.

PMID- 15740915
TI  - Simultaneous non-destructive determination of two components of combined
      paracetamol and amantadine hydrochloride in tablets and powder by NIR
      spectroscopy and artificial neural networks.
AB  - The two components (paracetamol and amantadine hydrochloride) were simultaneously
      determined in combined paracetamol and amantadine hydrochloride tablets and
      powder by using near-infrared (NIR) spectroscopy and artificial neural networks
      (ANNs). The ANN models of three pretreated spectra (first-derivative, second
      derivative and standard normal variate (SNV), respectively) were established. The
      mathematical corrected models of tablets were compared with those of the powder.
      In the models, the concentrations of paracetamol and amantadine hydrochloride as
      the active components were determined simultaneously and compared with the
      results of their separate determination. The parameters that affected the network
      were studied and the concentrations of the test set samples were predicted. The
      degree of approximation, a new evaluation criterion of the network was employed
      to prove the accuracy of the predicted results.

PMID- 15740916
TI  - Determination of protamine peptides in insulin drug products using reversed phase
      high performance liquid chromatography.
AB  - This paper describes the establishment and validation of a reversed phase HPLC
      (RP-HPLC) method for determination of protamine peptides in protamine sulphate
      raw material and insulin drug products, discusses the analytical results obtained
      for a number of protracted insulin formulations and the potential of the method
      in connection with protamine sulphate raw material and final drug product quality
      control.

PMID- 15740917
TI  - Development and validation of a stability indicating HPLC method for
      determination of lisinopril, lisinopril degradation product and parabens in the
      lisinopril extemporaneous formulation.
AB  - The purpose of the research described herein was to develop and validate a
      stability-indicating HPLC method for lisinopril, lisinopril degradation product
      (DKP), methyl paraben and propyl paraben in a lisinopril extemporaneous
      formulation. The method developed in this report is selective for the components
      listed above, in the presence of the complex and chromatographically rich matrix
      presented by the Bicitra and Ora-Sweet SF formulation diluents. The method was
      also shown to have adequate sensitivity with a detection limit of 0.0075
      microg/mL (0.03% of lisinopril method concentration). The validation elements
      investigated showed that the method has acceptable specificity, recovery,
      linearity, solution stability, and method precision. Acceptable robustness
      indicates that the assay method remains unaffected by small but deliberate
      variations, which are described in ICH Q2A and Q2B guidelines.

PMID- 15740918
TI  - Comparative study of the continuous wavelet transform, derivative and partial
      least squares methods applied to the overlapping spectra for the simultaneous
      quantitative resolution of ascorbic acid and acetylsalicylic acid in effervescent
      tablets.
AB  - The simultaneous spectrophotometric determination of ascorbic acid (AA) and
      acetylsalicylic acid (ASA) in effervescent tablets in the presence of the
      overlapping spectra was accomplished by the continuous wavelet transform (CWT),
      derivative spectrophotometry (DS) and partial least squares (PLS) approaches
      without using any chemical pre-treatment. CWT and DS calibration equations for AA
      and ASA were obtained by measuring the CWT and DS amplitudes corresponding to
      zero-crossing points of spectra obtained by plotting continuous wavelet
      coefficients and first-derivative absorbance values versus the wavelengths,
      respectively. The PLS calibration was constructed by using the concentration set
      and its full absorbance data consisting of 850 points from 220 to 305 nm in the
      range of 210-310 nm. These three methods were tested by analyzing the synthetic
      mixtures of the above drugs and they were applied to the real samples containing
      two commercial pharmaceutical preparations of subjected drugs. A comparative
      study was carried out by using the experimental results obtained from three
      analytical methodologies and precise and accurate results were obtained.

PMID- 15740919
TI  - Stability indicating reversed-phase ion-pairing liquid chromatographic
      determination of vertilmicin sulfate as bulk drug and in injections.
AB  - A simple reversed-phase high performance liquid chromatographic method was
      developed for the analysis of vertilmicin sulfate, a novel aminoglycoside (AG).
      UV detection was used to determine vertilmicin sulfate and its related compounds
      in drug substance and products without sample derivatization. The method was used
      to determine the content of vertilmicin and its related compounds and test the
      stability of vertilmicin sulfate as drug substance and in injections, which was
      required for registration of new drug.

PMID- 15740920
TI  - Chromatographic determination of polymerized impurities in meropenem.
AB  - A method for the separation of polymerized impurities in meropenem has been
      developed by gel filtration chromatography (GFC). The chromatographic conditions
      included a Superdex peptide HR 10/30 column and the mobile phase consisting of
      0.01 mol L(-1) sodium phosphate buffer (pH 7.0), at a flow rate of 0.8 mL min(
      1). The wavelength of UV detector was set at 220 nm. The linear range was 0.08-10
      microg (r=0.9998); relative standard deviation (R.S.D.)=0.5-1.5%; the LOD and LOQ
      were 2.4 and 12.4 ng, respectively. Specificity of the GFC was checked by
      switching the effluent of each peak on the GFC to a C18 trap column and analyzing
      the effluent by LC-MS. The result shows that for the determination of polymers,
      the gel filtration chromatography is a rather simple separation mode as compared
      to RPLC.

PMID- 15740921
TI  - Stereospecific high-performance liquid chromatographic analysis of hesperetin in
      biological matrices.
AB  - A method of analysis of hesperetin (+/--3,5,7-trihydroxy-4'-methoxyflavanone) in
      biological fluids is necessary to study the kinetics of in vitro and in vivo
      metabolism and tissue distribution. A simple high-performance liquid
      chromatographic method was developed for simultaneous determination of hesperetin
      enantiomers in rat serum, and rat and human urine. Serum and urine (0.1 ml) were
      precipitated with cold acetonitrile after addition of the internal standard, 7
      methoxycoumarin. Separation was achieved on a Chiralpak AD-RH column with UV
      detection at 298 nm. The calibration curve was linear ranging from 0.5 to 100
      microg/ml for each enantiomer. The mean extraction efficiency was >98%. Precision
      of the assay was <5% (CV), and was within 5% at the limit of quantitation (0.5
      microg/ml). Bias of the assay was lower than 5%, and was within 5% at the limit
      of quantitation. The assay was applied successfully to the urinary excretion of
      hesperetin in rats and humans.

PMID- 15740922
TI  - LC determination of citral in Cymbopogon citratus volatile oil.
AB  - It was the aim of this study to develop and validate a HPLC method for the
      quantitative determination of citral in Cymbopogon citratus volatile oil. The
      HPLC assay was performed using a Spherisorb CN column (250 mm x 4.6 mm, 5
      microm), a n-hexane:ethanol (85:15) mobile phase and an UV detector (set at 233
      nm). The following parameters were evaluated: linearity, precision, accuracy,
      specificity, quantification and detection limits. The method showed linearity in
      the range of 10.0-30.0 microg ml(-1). Precision and accuracy were determined at
      the concentration of 20 microg ml(-1). The concentration of citral in C. citratus
      volatile oil obtained with this assay was 75%. The HPLC method developed in this
      study showed an excellent performance (linearity, precision, accuracy and
      specificity) and can be applied to assay citral in volatile oil.

PMID- 15740923
TI  - Narrow-bore high performance liquid chromatographic method for the determination
      of cetirizine in human plasma using column switching.
AB  - An improved column switching high performance liquid chromatographic (HPLC)
      method was developed for determination of cetirizine in human plasma. Plasma
      samples were prepared by liquid-liquid extraction using methylene chloride. The
      samples extracted were initially injected into a clean-up Capcell Pak MF C8
      column and the peaks of cetirizine and internal standard were separated to an
      analytical C18 micro-column via column switching device. This analysis showed
      highly sensitive and selective results. Also, it was successfully applied to
      evaluate the pharmacokinetics of cetirizine in human volunteers after single oral
      administration.

PMID- 15740924
TI  - Combinatorial screening employing nylon loops and micro-X-ray powder diffraction.
AB  - A combinatorial screening method is described that employs nylon loops and micro
      X-ray powder diffraction. The nylon loops are used to position the sample in a
      three-circle X-ray diffractometer in such a way as to allow for Gandolfi-like
      scans. These scans maximize mechanical tumbling of the sample, which in turn
      results in higher quality data. The diffractometer utilizes a pinhole source and
      two-dimensional area detection for rapid data collection. The method can be
      readily automated by employing single-crystal screening procedures. The
      combinatorial analysis of the three known polymorphs of D-mannitol is discussed
      and a simple procedure to produce all three polymorphs from the same starting
      solutions is presented.

PMID- 15740925
TI  - Simultaneous determination of luteolin and apigenin in dog plasma by RP-HPLC.
AB  - A specific and accurate high-performance liquid chromatographic method has been
      developed and validated for the simultaneous determination of luteolin and
      apigenin in the plasma of dog. The sample was treated with 6.0% perchloric acid
      to precipitate the protein. Luteolin and apigenin were extracted with ethyl
      acetate. The organic layer separated was dried and reconstituted in the mobile
      phase. The HPLC separation was performed on C18 column and the UV detector was
      set at 350 nm. The standard curve for luteolin and apigenin in plasma were linear
      over the range of 38.5-4350 and 16.5-1860 ng/ml, with the correlation
      coefficients 0.9996 and 0.9999, respectively. The assay recoveries for luteolin
      and apigenin ranged from 102.7 to 104.5% and 93.8-101.8%, respectively. The intra
      and inter-day precisions (R.S.D.) for luteolin and apigenin were all less than
      7.9%. The sample was stable within 24 h at 4 degrees C storage, 30 days at -20
      degrees C storage, and undergoing four freeze-thaw-assay cycles. The limits of
      detection (LOD) of luteolin and apigenin were 1.82 and 1.94 ng/ml, while the
      limits of quantification (LOQ) were 7.84 and 6.29 ng/ml, respectively. The method
      developed was applied successfully to study pharmacokinetics of the effective
      composition (luteolin) of Chrysanthemum morifolium extract in dogs after single
      dose of oral administration.

PMID- 15740926
TI  - High-performance liquid chromatographic determination of sumatriptan after in
      vitro transdermal diffusion studies.
AB  - A simple, accurate, precise and rapid HPLC method with UV detection has been
      validated in order to determine the in vitro transdermal absorption of
      sumatriptan succinate. The HPLC method is a modification of that described by
      Nozal et al. [M.J. Nozal, J.L. Bernal, L. Toribio, M.T. Martin, F.J. Diez, J.
      Pharm. Biomed. Anal. 30 (2002) 285-291]. Separation was carried out on a 250 mm
      Kromasil C18 column at room temperature. The detector response, at 282.7 nm, was
      found to be linear in a concentration range between 0.145 and 145 microM. The
      limit of detection (LOD) was 0.019 microM and the limit of quantification (LOQ)
      was 0.145 microM.

PMID- 15740927
TI  - Quantitative analysis of enalapril by 1H NMR spectroscopy in tablets.
AB  - A simple, rapid, accurate and selective 1H NMR method was developed for
      quantitative determination of enalapril maleate in pharmaceutical preparations.
      Spectra were determined in D2O, using L-leucine as internal standard. Both
      synthetic mixtures and commercial dosage forms were assayed, and the results were
      compared to those obtained using the USP XXIV procedure and were both in close
      agreement.

PMID- 15740928
TI  - Effects of nifedipine, verapamil and diltiazem on serum biochemical parameters
      and aortic composition of atherosclerotic chickens.
AB  - Calcium appears to be involved in many of the cellular events, which are thought
      to be important in atherogenesis. In this study, we examine the effects of three
      calcium entry blockers (nifedipine, verapamil, and diltiazem at clinical and
      higher doses) on serum biochemical parameters and aortic calcium, cholesterol and
      triglyceride concentrations of atherosclerotic egg-fed chickens. All egg-fed
      chickens (treated and non-treated) showed an increase in serum total cholesterol,
      LDL-cholesterol and triglycerides without significant effect when calcium entry
      blockers were used. Increased HDL values were observed in clinical and high-dose
      nifedipine and clinical dose verapamil groups. The high-dose diltiazem group
      presented increased zinc values with respect to the clinical dose diltiazem and
      control groups. The sodium concentrations were significantly decreased in all the
      groups of animals treated with calcium entry blockers at high-doses and
      nifedipine at clinical doses. Measurements of aortic calcium concentration showed
      a significant decrease in the high-dose nifedipine and verapamil groups. Calcium
      channel blockers had a tendency to decrease total cholesterol in aortas. The
      values were statistically significant for the high-dose verapamil, and nifedipine
      groups. Only nifedipine showed a significant decrease for this parameter at
      clinical dosages. Triglyceride concentrations in aortas were significantly low in
      animals fed an atherogenic diet and treated with calcium channel blockers,
      without differences between drugs or dosages used in the experiment. In addition,
      the chicken atherosclerosis model has proved itself useful and very suitable for
      in vivo drug intervention studies.

PMID- 15740929
TI  - Decrease of arterial stiffness at common carotid artery in hypothyroid patients
      by normalization of thyroid function.
AB  - This study examined the effect of hypothyroidism on arterial stiffening and the
      effect of levothyroxine (l-T(4)) replacement. The arterial stiffness index beta
      (stiffness beta) and intima-media thickness (IMT), a parameter of arterial
      stiffening and thickening, respectively, were determined in common carotid artery
      (CCA) by ultrasonography in 30 hypothyroid patients before and after 1 year of
      normalization of thyroid function by l-T(4) replacement. Baseline CCA stiffness
      beta and IMT was significantly higher in the hypothyroid patients than in age-
      and sex-matched normal controls [9.46 +/- 0.93 vs. 8.02 +/- 0.91 (mean +/- SE); P
      < 0.05, 0.635 +/- 0.018 mm vs. 0.541 +/- 0.019 mm; P < 0.005, respectively]. In
      multivariate analysis, baseline stiffness beta was significantly associated with
      baseline levels of IMT (r = 0.457, P = 0.0311), FT(4) (r = -0.413, P = 0.0169),
      and a plasma vascular injury marker, von Willebrand factor (vWF) (r = 0.412, P =
      0.0261). During 1 year of euthyroidism, 22 and 29 out of 30 patients showed
      significant decreases of stiffness beta and IMT to normal respective level, from
      9.46 +/- 0.93 to 7.58 +/- 0.34 and from 0.635 +/- 0.018 to 0.552 +/- 0.015 mm,
      respectively. Change in stiffness beta during l-T(4) therapy correlated
      significantly in a negative manner with baseline levels of age (r = -0.465, P =
      0.011) and IMT (r = -0.406, P = 0.029). Stiffness beta after but not before l
      T(4) therapy showed a tendency towards a positive correlation with age. This
      study suggested that increases of arterial thickening, and plasma vWF, and a
      reduction in serum FT(4) might have an important role independently in the
      increased arterial stiffening in hypothyroid patients. Furthermore, it was
      demonstrated that sustained euthyroidism might have the potential to reverse
      arterial stiffening in addition to thickening in hypothyroid patients.

PMID- 15740930
TI  - Effect of nebivolol on QT dispersion in hypertensive patients with left
      ventricular hypertrophy.
AB  - Hypertensive patients with left ventricular hypertrophy (LVH) have increased QT
      dispersion, which is considered an early indicator of end-organ damage and a non
      invasive marker of risk for clinically important ventricular arrhythmias and
      cardiac mortality. The purpose of this study was to examine the effect of
      nebivolol antihypertensive therapy on QT dispersion in hypertensive subjects.
      Twenty-five subjects (15 men and 10 women, mean age 53.6 +/- 4.5 years) with
      essential arterial hypertension and mild-to-moderate LVH (blood pressure: 147.2
      +/- 6.2/90.6 +/- 3.8 mmHg; left ventricular mass indexed: 149.1 +/- 10.7 g/m(2))
      were compared with 25 age-matched healthy control subjects. All the participants
      underwent a complete clinical examination, including electrocardiogram for QT
      interval measurements. The QT dispersion was defined as the difference between
      the longest and the shortest QT interval occurring in the 12-lead
      electrocardiogram. The QT dispersion was corrected (QTc) with Bazett's formula.
      Hypertensive subjects were treated with 5 mg daily of nebivolol. The ECG and
      echocardiogram were repeated after four weeks of treatment. At baseline,
      hypertensive patients showed QT dispersion (56.9 +/- 6.4 vs. 31.7 +/- 8.4 ms, P <
      0.001) and QTc dispersion (58.3 +/- 6.2 vs. 33.2 +/- 7.8 ms, P < 0.001)
      significantly higher than control subjects. Four-week nebivolol treatment reduced
      blood pressure from 147.2 +/- 6.2/90.6 +/- 3.6 mmHg to 136.3 +/- 3.1/83.3 +/- 2.5
      mmHg (P < 0.0001), and resting heart rate from 75.3 +/- 4.7 to 64.2 +/- 3.0 bpm
      (P < 0.001), without significant change in left ventricular mass (LVMi: 149.1 +/-
      10.7 vs. 151.4 +/- 9.8 g/m(2), ns). Nebivolol-based treatment improved QT
      dispersion (56.9 +/- 6.4 vs. 40.5 +/- 5.8 ms, P < 0.001) and QTc dispersion (58.3
      +/- 6.2 vs. 42.2 +/- 5.6 ms, P < 0.001), which remained higher than in control
      subjects (P < 0.001 in both cases). The reduction of QT dispersion did not
      correlate with arterial BP reduction. In conclusion, nebivolol reduced increased
      QT dispersion in hypertensive subjects after four weeks. This effect, occurred
      without any change in LVM, did not seem to be related to the blood pressure
      lowering and could contribute to reduce arrhythmias as well as sudden cardiac
      death in at-risk hypertensive patients.

PMID- 15740931
TI  - Plasma N-terminal pro-brain natriuretic peptide and brain natriuretic peptide in
      assessment of acute dyspnea.
AB  - We examined the analytical correlation between non-radioimmunometric plasma N
      terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide
      (BNP) and evaluated whether NT-proBNP or BNP was superior in the emergency
      diagnosis of heart failure and whether this was influenced by age, gender, body
      mass index (BMI) and renal function. Data were collected prospectively from
      patients admitted to the emergency department for acute dyspnea. Plasma BNP
      (Triage, Biosite) and NT-proBNP (Elecsys, Roche diagnostic(R)) were measured at
      admission in addition to other standard biological parameters and clinical
      variables. Reference diagnosis was adjudicated by two independent cardiologists
      using the European society of cardiology guidelines. We evaluated the influence
      of creatinine clearance, age, gender and BMI on plasma BNP and NT-proBNP levels.
      One hundred and sixty consecutive patients were included: 84 females and 76
      males, mean age 80.1 + 13.5 (16-98). The analytical correlation between the
      automated electro-chemiluminescence immunoassay for NT-proBNP and the single use
      fluorescence immunoassay for BNP was satisfactory using the equation: NT-proBNP =
      1.1 BNP + 0.57 and a correlation r = 0.93. This was established over a wide range
      of concentration (5-6400 pg/ml for BNP). Areas under receiver operating
      characteristic (ROC) curve for BNP and NT-proBNP as a diagnostic marker for heart
      failure were 0.82 and 0.84, respectively and a BNP level of 150 pg/ml has similar
      sensitivity and specificity that NT-proBNP level of 1000 pg/ml. The correlation
      was not influenced by age, gender and BMI of patients. Renal dysfunction did not
      affect significantly this correlation (r = 0.93). We conclude that NT-proBNP, as
      assayed in the present study, correlates closely with BNP. This correlation is
      only slightly modulated by creatinine clearance values. The NT-proBNP appears as
      accurate as BNP according to area under ROC curve. Used in conjunction with other
      clinical information, rapid measurement of BNP or NT-proBNP is useful in
      establishing or excluding the diagnosis of congestive heart failure in patients
      with acute dyspnea.

PMID- 15740932
TI  - Antihypertensive effect of oral potassium aspartate supplementation in mild to
      moderate arterial hypertension.
AB  - BACKGROUND: Previous studies showed that potassium chloride (48-120 mmol/day)
      supplementation reduced arterial blood pressure (BP) in hypertensive patients.
      OBJECTIVES: Our aim was to evaluate the effect of a lower dose of potassium
      aspartate salt on BP in individuals with essential arterial hypertension.
      METHODS: One hundred and four patients (65 males, age 53 +/- 12 years) with mild
      to moderate essential hypertension (systolic/diastolic BP 154.2/96.2 +/- 10.8/5.4
      mmHg) were allocated in two comparable groups of 52 to receive or not 30 mmol/day
      per os of potassium aspartate supplementation for four weeks. Office and 24-h BP,
      as well as serum and urinary electrolytes, were measured at baseline and at the
      follow-up visit after four weeks. RESULTS: Office and 24-h BP did not change in
      the control group, while these values were significantly reduced in the potassium
      supplementation group. Changes in office (systolic BP: 154.4 +/- 8.2 vs. 142.2 +/
      7.6 mmHg; diastolic BP: 95.0 +/- 5.6 vs. 87.2 +/- 4.3 mmHg, P < 0.001 for both)
      and 24-h BP (systolic BP: 142.7 +/- 8.2 vs. 134.8 +/- 6.3 mmHg; diastolic BP:
      90.8 +/- 4.4 vs. 84.6 +/- 3.8 mmHg, P < 0.001 for both) following potassium
      supplementation were highly significant. The changes in day time and night time
      BP were similar. The treated group showed significantly increased potassium serum
      level and 24-h urinary excretion of potassium (P < 0.01 in both cases) after four
      weeks, while the untreated group showed no significant changes of the same
      parameters. Urinary Na/K ratio decreased significantly with potassium
      supplementation (P < 0.001). In the treated group changes in office (r = 0.58, P
      < 0.001) and 24-h SBP (r = 0.51, P < 0.001), but not in DBP (r = 0.29 and r =
      0.25, n.s.), correlated positively with the urinary Na/K ratio at baseline.
      CONCLUSIONS: A relatively low supplementation of 30 mmol/day of potassium as
      aspartate lowered office and 24-h ambulatory BP in subjects with mild to moderate
      essential hypertension. The antihypertensive effect was sustained throughout the
      day, and was greater in the patients with high basal urinary Na/K ratio.

PMID- 15740933
TI  - Renal glomerular permselectivity and vascular endothelium.
AB  - The glomerular barrier is the kidney's physical block to the unrestricted flow of
      molecules from the plasma into the urinary space. Its exquisite selectivity
      allows solutes and water in the glomerular capillaries to pass through but it
      prevents the bulk of plasma proteins, most notably albumin, from crossing.
      Classically the barrier consists of three components: glomerular endothelium,
      glomerular basement membrane and glomerular epithelium (podocytes) with slit
      diaphragm. A lot of investigations are experimental but they are sufficient to
      show the pivotal role of endothelium in glomerular proteinuria. In this study the
      author discuss glomerular endothelium with particular emphasis on the barrier
      presumed to be imparted by endothelium-glomerular basement membrane-podocyte
      interactions. By specialized glomerular endothelial structure (caveolae, tight
      junctions, endothelium glycocalyx) and by circulating permeability factors
      (albumin, orosomucoid, apolipoproteins, Amadori's products). Concluding remarks
      underline the significance to study the glomerular vascular endothelial
      dysfunction.

PMID- 15740934
TI  - Analysis of IGG and IGG4 in HIV-1 seropositive patients and correlation with
      biological and genetic markers.
AB  - We have compared the levels of immunoglobulins G (IgG) and G4 (IgG4) in extreme
      seropositive patients from the GRIV cohort consisting of 168 patients with slow
      progression (SP) and 60 with rapid progression (RP) as well as in 173 healthy
      controls. IgG levels were significantly higher in SP patients than in RP patients
      (P = 0.008), both higher than in seronegative individuals. IgG4 levels were
      significantly lower in SP patients than in RP patients (P = 0.001), both lower
      than in seronegative individuals. We tried to correlate these levels with
      biological parameters (CD4(+) and CD8(+) cells, total lymphocytes, white blood
      cell counts, percentage of CD4(+) cells, and viral load) as well as with genetic
      markers from Th1/Th2 cytokines (IL2, IL4, IL6, IL10, IL13, and IFNgamma). IgG
      levels were correlated with the percentage of CD4(+) cells in SP while IgG4
      levels were correlated with CD8(+) cell count in SP and with percentage of CD4(+)
      cells in RP patients. Among the parameters measured in SP patients at the time of
      inclusion in the study, the best predictor of progression towards AIDS was the
      viral load, the best predictor for stability was CD4(+) cell count, but overall,
      the best predictor for SP evolution (stability vs. progression) appeared to be
      the percentage of CD4(+) cells. Interestingly, correlations between the levels of
      IgG or IgG4 and the cytokine gene polymorphisms were found, notably in the IL10
      gene.

PMID- 15740935
TI  - Synergistic anti-viral effect of oxanosine and ddI against human immunodeficiency
      virus.
AB  - The combined effect against human immunodeficiency virus (HIV) of oxanosine and
      2'3'-dideoxyinosine (ddI) has been evaluated by the production of viral
      particles, the expression of viral antigens on cell surfaces, and the amount of
      viral genome integrated in the host cells. Oxanosine alone has no effect on HIV
      replication up to 100 microg/ml, however, in the presence of ddI, oxanosine
      revealed concentration dependent inhibition against HIV without cytotoxicity.

PMID- 15740936
TI  - Synthesis of aryl semicarbazones as potential anticonvulsant agents.
AB  - A series of 4-ethoxyphenyl semicarbazones (1-10) have been synthesized using an
      appropriate synthetic route and characterized by elemental analyses and spectral
      data. The anticonvulsant activity of all the synthesized compounds was evaluated
      against maximal electroshock induced seizures (MES) and subcutaneous
      pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was
      assessed using the rotorod method. All the test compounds were administered at
      doses of 30, 100, and 300 mg/kg body weight and the anticonvulsant activity was
      noted at 0.5 and 4 h time intervals after the drug administration. Among the
      compounds tested, compounds except 3, 4 and 10 showed protection from seizures in
      both the animal models. Compounds 6 and 8 were found to increase gamma
      aminobutyric acid (GABA) levels in the medulla oblongata region of the rat brain.

PMID- 15740937
TI  - Cimetidine inhibits angiogenesis and suppresses tumor growth.
AB  - Cimetidine, a histamine type-2 receptor antagonist, has been reported to improve
      survival of patients with cancers. However, the exact mechanisms by which
      cimetidine suppresses development of cancers remain to be elucidated. Solid
      tumors require neovascularization for their growth. Here, we investigated the
      effects of cimetidine on tumor growth and angiogenesis. Syngeneic colon cancer
      cells, CMT93 cells, were inoculated into the subcutaneous space of C57BL/6 mice.
      Mice were treated with either saline or cimetidine. Tumor size was measured
      everyday and angiogenesis was evaluated histologically. Cimetidine markedly
      suppressed tumor growth with reduced neovascularization in the tumor. Cimetidine
      had no effect on proliferation of CMT93 cells in vitro. Vascular endothelial
      growth factor production by cancer cells was not affected by cimetidine, while
      vascular-like tube formation by endothelial cells in vitro was significantly
      impaired in the presence of cimetidine. Our findings suggest that cimetidine
      suppresses tumor growth, at least in part, by inhibiting tumor-associated
      angiogenesis.

PMID- 15740938
TI  - The incidence of gastroesophageal reflux after transthoracic esophagocardio
      myotomy without fundoplication: a long term follow-up.
AB  - OBJECTIVE: Evaluation of the long term results of Heller's myotomy performed over
      a lateral thoracotomy without additional fundoplication. METHODS: Forty patients
      (17 males, 23 females; mean age 43.2 years; range: 14-63 years) were operated
      between 1985 and 2000. Preoperative evaluation included clinical scoring of
      symptoms, esophagogram, endoscopy, manometry and 24-h ph-metry. At the follow-up
      investigation, the preoperative evaluation was repeated in all patients, adding a
      histological workup of the distal esophageal mucosa. The mean duration of follow
      up after surgery was 10.3 years, ranging from 3-16 years. RESULTS: The clinical
      scores improved significantly: Excellent relief from dysphagia was present in
      86%, little or no regurgitation was found in 79%, little or no retrosternal
      spasms were reported by 72% of the patients. Esophagogram showed an overall
      esophageal dilatation in all patients but no significant obstruction at the
      esophagogastric junction. Endoscopically, 2.5% had candida-esophagitis, 5% showed
      signs of a GERD I, 92.5% had a macroscopically insuspect esophageal mucosa.
      Histologically, 53% showed a mild chronic inflammation. Manometry demonstrated
      distinct hypomotility of the esophagus in all cases, yet no elevated pressure of
      the lower sphincter; pH-metry showed moderate reflux in 46%. CONCLUSIONS:
      Transthoracic cardiomyotomy is a valid method for the treatment of achalasia, but
      it will not improve the esophageal motility, which slowly deterioriates in these
      cases. The patient's subjective assessment of the postoperative result was
      positive in the majority of cases. Although fundoplication was not done in any of
      these patients, none of them showed signs of clinically relevant reflux.

PMID- 15740939
TI  - Manubriotomy versus median sternotomy in thymectomy for myasthenia gravis.
      Evaluation of the pulmonary status.
AB  - OBJECTIVE: In a prospective study, the effect of thymectomy on the pulmonary
      status of 50 consecutive patients with myasthenia gravis was evaluated over a
      time range of 4 years in the Chest and Chest surgery departments in the Cairo
      University Clinics and Thoracic Surgery Department of the Evangelisches
      Krankenhaus Duisburg-Nord. METHODS: The patients were divided into two groups:
      Group I included 26 patients who underwent thymectomy through median sternotomy.
      The mean age of the patients in this group was 24.8+/-10.5 (5-41) years. They
      were 19 females and seven males. Thirteen of the patients were in Myasthenia
      Gravis Foundation of America (MGFA) class IIa, and 12 were in class IIb, and one
      was in class IIIa. Group II included 24 patients who underwent thymectomy through
      manubriotomy. The mean age of the patients in this group was 25.2+/-9.2 (12-41)
      years. They were 13 females and 11 males. Eight of the patients were in MGFA
      class 2a, 14 were in class IIb, and two were in class IIIa. RESULTS: When
      compared to group I in which postoperative ventilation was required in 15.4% of
      patients, postoperative ventilation was not necessary in patients of group II
      with a statistically significant difference (P=0.04). The mean duration of stay
      in the intensive care unit was 111.4h in group II, and 169.7h in group I
      (P=0.03). The peak inspiratory flow rate and the forced vital capacity were also
      statistically significantly better in group II. There was no mortality in both
      groups, and the morbidity was higher in the median sternotomy group. CONCLUSION:
      Thymectomy through a manubriotomy, which allows extensive removal of ectopic
      thymic tissue in addition to the thymus through a less invasive approach than a
      full median sternotomy, is associated with a significantly smoother postoperative
      course and less pulmonary complications, when compared with thymectomy through a
      full median sternotomy.

PMID- 15740940
TI  - Inability to perform maximal stair climbing test before lung resection: a
      propensity score analysis on early outcome.
AB  - OBJECTIVE: The objective of the present study was to assess whether patients
      unable to perform a preoperative maximal stair climbing test had an increased
      incidence of morbidity and mortality after major lung resection compared to
      patients who were able to exercise. METHODS: Three hundred and ninety one
      patients submitted to pulmonary lobectomy or pneumonectomy for lung cancer were
      analyzed. Forty-five of these patients were unable to perform a preoperative
      maximal stair climbing test for underlying comorbidities. Unadjusted and
      propensity score case matched comparisons were performed between patients who
      could and who could not perform a preoperative stair climbing test. Multi
      variable analyses were then performed to identify predictors of morbidity and
      mortality, and were validated by bootstrap bagging. RESULTS: Patients who could
      not perform the stair climbing test had similar morbidity rates (31.1 vs. 35.6%,
      respectively, P=0.7), but higher mortality rates (15.6 vs. 4.4%, respectively,
      P=0.08) and deaths among complicated patients (50 vs. 12.5%, respectively,
      P=0.025), compared to propensity score matched patients who could perform the
      stair climbing test. Logistic regression analyses showed that the inability to
      perform the stair climbing test was an independent and reliable predictor of
      mortality (P=0.005) but not of morbidity (P=0.2). CONCLUSIONS: Patients unable to
      perform a preoperative maximal exercise test had an increased risk of mortality
      after major lung resection. Half of these patients did not survive postoperative
      complications, due to their decreased aerobic reserve caused by physical
      inactivity which made them unable to cope with the increased oxygen demand.

PMID- 15740941
TI  - Extra-pleural pneumonectomy for malignant pleural mesothelioma: the risks of
      induction chemotherapy, right-sided procedures and prolonged operations.
AB  - OBJECTIVE: With the increasing incidence of malignant pleural mesothelioma and
      renewed interest in radical surgery as a therapeutic option, we have examined our
      experience of extra-pleural pneumonectomy, to document the incidence and
      management of its peri-operative complications. METHODS: This analysis was
      conducted using prospectively entered data contained within the departmental
      database, with additional information from retrospective case note review.
      Details of patient selection criteria and operative modifications are included.
      RESULTS: Over a 59-month period, extra-pleural pneumonectomy was carried out on
      74 patients (66 men; 8 women; median age 57 years). Fifteen patients (20%)
      received cisplatin-doublet induction chemotherapy. The majority (80%) of patients
      had epithelial tumours and 85% of patients had disease in International
      Mesothelioma Interest Group stages III and IV. The 30-day post-operative
      mortality was 6.75% (five patients) and significant morbidity was recorded in 47
      patients (63%). Major complications included those of technical origin
      (diaphragmatic patch dehiscence 8.1%; chylothorax 6.7%; intra-thoracic
      haemorrhage 6.7%; bronchopleural fistula 6.7%), cardiovascular morbidity (atrial
      fibrillation 17.5%; mediastinal shift with subacute tamponade 10.8%; right
      ventricular failure 4%; pulmonary embolus 2.7%) and respiratory morbidity
      (pneumonia 10.8%; acute lung injury 8.1%). Admission to intensive care was
      required in 19 patients (26%). Univariate analysis identified the incidence of
      acute lung injury and mediastinal shift to be significantly associated with
      induction chemotherapy (P=0.005 and 0.014, respectively). In addition to this,
      laterality of operation influenced respiratory morbidity (P=0.018) and admission
      to intensive care (P=0.025). Finally, prolonged operations (greater than the
      median) were associated with an increased risk of technical (P=0.018) and gastro
      intestinal (P=0.023) complications. CONCLUSIONS: Extra-pleural pneumonectomy is
      associated with a high rate of morbidity, but an acceptable mortality rate can be
      achieved with increasing peri-operative experience. Surgery following induction
      chemotherapy requires extra vigilance for the development of post-operative
      respiratory complications.

PMID- 15740942
TI  - Postresectional pulmonary oxidative stress in lung cancer patients. The role of
      one-lung ventilation.
AB  - OBJECTIVE: The authors conducted a prospective analysis in order to investigate
      through lipid peroxidation metabolites the generation of oxygen free radicals
      after one-lung ventilation (OLV). METHODS: From 2001 to 2003, 212 patients were
      prospectively studied for lung reexpansion/reperfusion injury. They were
      classified in six groups. Group A, non-OLV lobectomy group; B, OLV pneumonectomy
      group; C-E, OLV lobectomy of 60, 90, and 120 min duration, respectively; F,
      normal subjects as baseline group. Preoperative, intraoperative and postoperative
      strict blood sampling protocol was followed. Malondialdehyde (MDA) plasma levels
      were measured. The recorded values were analyzed and statistically compared
      between groups and within each one. RESULTS: Comparison of groups C-E (OLV) to
      all other documented significant (P<0.001) increase of MDA levels during lung
      reexpansion and for the following 12h. The magnitude of oxidative stress was
      related to OLV duration (group E>D>C, all P<0.001). The removal of cancer
      associated parenchyma led to MDA level decrease postoperatively (P<0.001)
      especially after pneumonectomy (A vs. B, P<0.001). CONCLUSIONS: (1) Lung
      reexpansion provoked severe oxidative stress. (2) The degree of the amount of
      generated oxygen free radicals was associated to the duration of OLV. (3)
      Patients with lung cancer had a higher production of oxygen free radicals than
      normal population. (4)Tumor resection removes a large oxidative burden from the
      organism. (5) Mechanical ventilation and surgical trauma are weak free radical
      generators. (6) Manipulated lung tissue is also a source of oxygen free radicals,
      not only intraoperatively but also for several hours later.

PMID- 15740943
TI  - Transcervical extended mediastinal lymphadenectomy--the new operative technique
      and early results in lung cancer staging.
AB  - OBJECTIVE: Mediastinal staging is one of the most important problems in thoracic
      surgery. Although the pathological examination is a generally accepted standard,
      none of the currently used techniques enables complete removal of all lymph node
      stations of the mediastinum. The aim of the study is to present a new technique
      of transcervical extended mediastinal lymphadenctomy (TEMLA) and to analyze its
      value in lung cancer staging. METHODS: In the prospective study of consecutive
      group of non-small cell lung cancer (NSCLC) patients, operated on between January
      and August 2004, we evaluated the usefulness of this original technique of
      bilateral mediastinal lymphadenectomy, assessing its accuracy and safety. The
      operations were performed through the transcervical approach, were
      videomediastinoscopy-assisted, with sternum elevation. Lymph node stations 1, 2R,
      2L, 3a, 4R, 4L, 5, 6, 7 and 8 were removed. In patients without mediastinal
      metastases thoracotomy with pulmonary resection was performed and mediastinum
      searched for any missed lymph nodes. RESULTS: There were 83 patients operated on
      with the TEMLA technique. The mean number of nodes removed was 43 (range: 26-85).
      The sensitivity, specificity and accuracy of the presented method in detecting
      mediastinal node metastases were: 90, 100, and 96%, respectively, whereas the
      positive and negative predictive values were: 100 and 95%, respectively.
      CONCLUSIONS: The TEMLA technique is a safe and highly accurate method of
      mediastinal staging in NSCLC.

PMID- 15740944
TI  - A prospective randomized controlled trial of suction versus non-suction to the
      under-water seal drains following lung resection.
AB  - OBJECTIVE: Practice varies as to whether or not suction is applied to under-water
      seal drains following lung surgery. We tested the null hypothesis that there is
      no difference with respect to air leak duration. METHODS: Patients undergoing
      thoracotomy or video assisted thoracoscopic surgery for lobectomy or wedge
      resection had either low-pressure suction or no suction applied to their
      underwater seal bottles postoperatively. Patients were allocated using
      minimization, a method of unbiased allocation ensuring balance between the arms
      of a trial with respect to known or suspected confounding factors. The trial was
      powered for duration of air leak. If an air leak persisted on the 7th post
      operative day, the surgeon determined further management. Kaplan-Meier survival
      analysis of air leak duration and a log rank test were performed on an intention
      to-treat basis, with observations censored at 144h (6 complete days). RESULTS: Of
      the 254 patients that entered the trial, data were available for analysis for 239
      (123 no-suction and 116 suction). There was no significant difference in the
      cumulative persistence of air leaks between the two groups (P=0.62) and
      inspection of the Kaplan-Meier curves suggests that any difference is negligible.
      CONCLUSIONS: Applying suction to the underwater seal drains following lung
      surgery makes no difference in terms of air leak duration. In the light of this
      finding we have adopted a uniform policy of no suction being applied to the
      underwater seal, from the time of surgery, unless a specific clinical judgment is
      made to use it. The anticipated gains are that this will reduce work and cost and
      aid mobilization.

PMID- 15740945
TI  - High-vacuum drains rival conventional underwater-seal drains after pediatric
      heart surgery.
AB  - OBJECTIVE: The collection of fluid in the mediastinum after cardiac surgery is
      traditionally prevented using underwater seal drains that may be connected to low
      pressure suction. High-vacuum drains (redivac drains) are a potential alternative
      to this arrangement and have previously been utilized in areas of general
      surgery, as well as in the treatment of post-sternotomy mediastinitis. There has
      been no study to date addressing the safety and efficacy of these drains
      following pediatric cardiac surgery. METHODS: Five hundred and forty-six patients
      were prospectively randomised to receive either the redivac drains or the
      conventional underwater-seal drains attached to low-pressure wall suction. We
      sought to test the null hypothesis that there was no difference in the incidence
      of residual pericardial or pleural collections requiring drainage between the 2
      drainage systems. Secondary endpoints included time to drain removal, volume of
      drainage and drain size. Analysis was performed on an intention to treat basis.
      RESULTS: Two hundred and thirty-seven patients were allocated to the redivac
      group, while 241 were allocated to the conventional drain group. Age and gender
      distribution, the use of cardiopulmonary bypass, numbers of patients with
      univentricular morphology and number of drains utilized were similar in the 2
      groups. The use of redivac drains resulted in a significantly lower incidence of
      residual pleural effusions requiring drainage (4 vs. 18, P=0.003). There was no
      difference in the incidence of pericardial effusion requiring drainage. Redivac
      drains drained an equivalent volume through smaller calibre tubes (12 Ch vs. 16
      Ch, P<0.0001) over a shorter period of time (42h (IQR 22-45) vs. 43h (IQR 27-52),
      P<0.01) than the conventional drainage system. CONCLUSIONS: Redivac drains are as
      safe and effective as conventional drains in the pediatric setting, and resulted
      in a lower incidence of residual pleural effusions requiring drainage. Together
      with their ease of care, earlier mobilisation of patients and greater cost
      effectiveness, the routine use of high-vacuum drains can be recommended following
      pediatric heart surgery.

PMID- 15740946
TI  - A forgotten old disease: mediastinal tuberculous lymphadenitis in children.
AB  - OBJECTIVE: The purpose of the study was two-fold: (1) to highlight the varied
      presentation of mediastinal tuberculous lymphadenitis (MTL) in children and (2)
      to identify parameters, that may help in the early diagnosis of this condition.
      METHODS: Between January 1995 and December 2002, 13 children with histological
      diagnosis of MTL were retrospectively assessed for age at presentation, history
      of exposure to TB, presenting symptoms, investigations, initial diagnosis,
      surgical treatment and outcome. Stepwise multiple linear regression analysis was
      used to determine potential risk factors for early diagnosis of MTL. RESULTS:
      Thirteen children presented with: (a) fever, night sweats and weight loss (4);
      (b) acute respiratory distress (2); (c) cough and shortness of breath (SOB) (5);
      (d) stridor (1); and (e) chest pain (1). TB was suspected only in 6 children
      (46%) at presentation. In the other 7 cases (54%) the presumed diagnoses were:
      neuroblastoma (n=1), metastatic malignancy (n=1), bronchial polyp (n=1),
      bronchogenic cyst (n=2), and presumed foreign body (n=2). Bronchoscopy was
      diagnostic in identifying cheesy material within the bronchus and organisms on
      lavage in 4 (30%) and in identifying external compression in 2 (15%). Thoracotomy
      and excision of the lymph node mass was necessary to treat the mediastinal
      compression and to ascertain the diagnosis of TB in 3 children (23%). All 13
      children had complete resolution of tuberculous lymphadenitis following anti
      tuberculous treatment. The diagnostic clues in this cohort of patients were cough
      and SOB with history of exposure to tuberculosis (P=0.0001) and bronchoscopy and
      lavage with positive staining for acid-fast bacilli (P=0.0001). CONCLUSIONS:
      Tuberculosis was not suspected in 54% of children with MTL, and they posed
      diagnostic dilemma on admission. Bronchoscopy must be used as a diagnostic tool
      in children where tuberculosis cannot be excluded by radiology or specific skin
      tests. Thoracotomy and excision may be necessary to treat the obstructive
      symptoms.

PMID- 15740947
TI  - Does Down syndrome affect the long-term results of complete atrioventricular
      septal defect when the defect is repaired during the first year of life?
AB  - BACKGROUND: Down syndrome is known to affect the natural history of complete
      atrioventricular septal defect. We analyzed whether Down syndrome affect the long
      term results of complete atrioventricular septal defect when the defect is
      repaired during the first year of life. METHODS: Repairs of complete
      atrioventricular septal defect were performed in 64 infants. Thirty-four infants
      were associated with Down syndrome, while the other 30 were non-Down patients.
      RESULTS: Complete follow-up rate was 95% with mean follow-up period of 99+/-47
      months (maximum 169 months) in Down patients and 80+/-64 months (maximum 213
      months) in non-Down patients. There was one operative death in each group
      (mortality rate of 2.9% in Down patients and 3.3% in non-Down patients), and
      three patients died at the late phase (one in Down patients and two in non-Down
      patients). Five patients underwent re-operation due to postoperative left
      atrioventricular valve regurgitation (one in Down patients and four in non-Down
      patients). Freedom from re-operation for left atrioventricular valve
      regurgitation and actuarial survival rate at 13 years were 96+/-4 and 94+/-4% in
      Down patients and 85+/-7 and 90+/-5% in non-Down patients (not significantly
      different). CONCLUSIONS: Down syndrome does not affect the long-term results of
      complete atrioventricular septal defect when the defect is repaired during the
      first year of life.

PMID- 15740948
TI  - Mid-term findings on echocardiography and computed tomography after RVOT
      reconstruction: comparison of decellularized (SynerGraft) and conventional
      allografts.
AB  - OBJECTIVE: The immune response against human-leucocyte-antigens on donor-cells
      may be an important factor contributing to the degeneration of allograft-valves.
      We have previously reported that the use of the decellularized allograft
      SynerGraft (CryoLife) reduces the immunologic response of the allograft
      recipient. In this study we compare the echocardiographic and computed tomography
      angiographic (CTA) findings of SynerGrafts with conventional cryopreserved
      allografts. METHODS: 22 patients who received a pulmonary SynerGraft (SG-group)
      (21 during a Ross-procedure) underwent CTA and resting echocardiography (median:
      10 months postoperatively). 47 randomly chosen patients who underwent a Ross
      procedure served as controls (C-group) (median: 32 months postoperatively).
      RESULTS: Neither the pressure gradients (mean: SG=9+/-4 vs C=10+/-4mmHg; P=0.64)
      across the allograft, nor the effective orifice area (EOAI) (SG=0.93+/-0.80 vs
      C=0.93+/-0.42cm(2)/m(2); P=0.96) differed between the groups. The EOAI showed a
      significant correlation with the smallest allograft-conduit-area measured on CTA
      (r=0.81; P<0.001) which was most frequently (n=34) found in the proximal
      postvalvular tubular part of the conduit. Calcifications (n=11) or a
      fibroproliferative reaction (n=15) were rarely observed. Overall, there were no
      radiologic differences between the groups. On CTA, the smallest diameter of the
      allograft-conduits was significantly smaller than the diameter given on the
      cryopreservation protocol (SG=16+/-3 and C=17+/-3mm vs 25mm in both groups;
      P<0.001 each) whereas the diameter of the distal part of the allograft was not
      (SG=24+/-2, P=0.066, and C=25+/-3mm, P=0.82). CONCLUSIONS: Despite a significant
      shorter follow-up in the SynerGraft-group, no functional or radiologic
      differences were observed as compared to control-patients. The smallest diameter
      is located almost exclusively at the proximal level of allograft-conduits.

PMID- 15740949
TI  - Clinical profile of post-operative ductal aneurysm and usefulness of sternotomy
      and circulatory arrest for its repair.
AB  - OBJECTIVE: Post-operative ductal aneurysm is a rare but fatal condition. We
      retrospectively analyzed the clinical profile of post-operative ductal aneurysm
      and outcome of their repair with different surgical approaches. METHODS: From
      January 1976 to December 2002, 13 patients underwent repair of post-operative
      ductal aneurysm. The case data of the patients operated were analyzed and
      survivors were followed-up. Three patients underwent repair through left
      thoracotomy, femoro-femoral bypass and 10 patients underwent patch aortoplasty
      through sternotomy using total circulatory arrest with minimal dissection. Among
      the sternotomy group, nine patients had midline sternotomy and one patient had
      transverse sternotomy with the patient in semi-right-lateral position. Hemoptysis
      (69%) was the commonest presenting symptom. Ten patients had ligation and three
      patients had division of ductus. Mean age at ductus interruption was 13.7+/-8.2
      years; mean time interval for development of aneurysm was 3.6+/-4.2 years; mean
      age at aneurysm surgery was 16.9+/-8.8 years. Residual left to right shunt was
      detected in 6 (46%) patients. RESULTS: Three patients repaired through left
      thoracotomy with femoro-femoral bypass died during surgery due to rupture of
      aneurysm during dissection and profuse bleeding. Thirty-day survival in patients
      operated through sternotomy using circulatory arrest was 90% (9/10). Two patients
      required additional incision in second left intercostal space along with midline
      sternotomy, for access to descending thoracic aorta. Of these two patients, one
      patient had bleeding from friable aorta and died; another patient developed left
      hemiplegia; circulatory arrest time was prolonged in this patient. Mean follow-up
      period was 9.6+/-5.3 years. Persistent left vocal cord palsy was seen in one
      patient. One patient was lost to follow-up after 3-years. Remaining eight
      patients were asymptomatic at follow-up. CONCLUSION: Repair of postoperative
      ductal aneurysm through left thoracotomy is difficult due to extreme fragility of
      aneurysm and because of reoperative difficulties. The immediate and long-term
      outcome of the cases operated through sternotomy using total circulatory arrest
      with minimal dissection is good. Midline sternotomy limits approach to descending
      thoracic aorta that can be circumvented by using transverse sternotomy with semi
      right-lateral positioning of the patient.

PMID- 15740950
TI  - Improved outcome with composite graft versus homograft root replacement for
      children with aortic root aneurysms.
AB  - OBJECTIVE: Review of surgical repair of aortic root aneurysms using composite
      graft or homograft in children. METHODS: A consecutive series of 34 children
      (mean age 10.8+/-5.4 years) who underwent elective aortic root replacement using
      composite graft or homograft from 1987 to 2003 (mean follow-up 5.7+/-3.7 years).
      RESULTS: Preoperatively, the aortic annulus and aortic root average z-scores were
      4.1+/-2.2 and 9.4+/-4.7, respectively. Composite graft root replacement was
      performed in 22 patients, and cryopreserved aortic homograft root replacement in
      12 patients. There was one perioperative death in the homograft group due to
      sudden cardiovascular collapse. There was one late death in the composite graft
      group due to acute aortic dissection, and two late deaths in the homograft root
      replacement group, one at 7 months postoperatively due to coronary artery
      thrombosis and one due to severe chronic myocardial dysfunction 5 years
      postoperatively. One patient who initially had a homograft died due to mechanical
      valve thrombosis following reoperative composite graft replacement. Five patients
      had reoperations at a median of 7.1 years after initial surgery. One patient in
      the composite graft group underwent arch replacement. There were no graft related
      reoperations after composite graft root replacement, but 4 patients in the
      homograft group had reoperative composite graft replacement. Predictors of
      reoperation included age at surgery, lower weight, and longer ICU time (P<0.05).
      CONCLUSIONS: In children with aortic root aneurysms, reoperation is more common
      after homograft root replacement than composite graft replacement. Composite
      graft root replacement provides more stable repair of the aortic root.

PMID- 15740951
TI  - Long-term outcomes of valve replacement with modern prostheses in young adults.
AB  - OBJECTIVES: To examine the multiple impacts of valve replacement on the lives of
      young adults. METHODS: Patients (N=500) between age 18 and 50 who had aortic
      valve replacement (AVR) and/or mitral valve replacement (MVR) with contemporary
      prostheses were followed annually. Events, functional status, and quality of life
      were examined with regression models. RESULTS: Median follow-up was 7.1+/-5.3
      years (maximum 26.7 years). Five, 10, and 15-year survival was 92.7+/-1.7, 88.3+/
      2.4 and 80.1+/-4.7% after AVR, and 93.1+/-2.3, 79.5+/-4.3 and 71.5+/-5.4% after
      MVR, respectively. Survival decreased with concomitant coronary disease (hazard
      ratio (HR): 4.5) and preoperative LV grade (HR: 2.0/grade increase) in AVR
      patients, and with atrial fibrillation (HR: 5.5), coronary disease (HR: 5.7),
      preoperative left atrial diameter (HR: 3.0/cm increase) and NYHA class (HR:
      2.1/class increase) in MVR patients. Despite reoperation, late survival was
      equivalent between bioprostheses and mechanical valves in both implant positions.
      The ten-year cumulative incidence of embolic stroke was 6.3+/-2.4% for mechanical
      AVR patients, 6.4+/-2.9% for bioprosthetic AVR patients, 12.7+/-3.9% for
      mechanical MVR patients, and 3.1+/-3.1% for bioprosthetic MVR patients. Atrial
      fibrillation (HR: 2.8) and smoking (HR: 4.0) were risk factors for stroke in MVR
      patients. In AVR patients, SF-12 physical scores, freedom from recurrent heart
      failure, and freedom from disability were significantly higher in bioprosthetic
      than mechanical valve patients. Career or income limitations were more often
      subjectively linked to a mechanical prosthesis in both implant positions.
      CONCLUSIONS: Late outcomes of modern prosthetic valves in young adults remain
      suboptimal. Bioprostheses deserve consideration in the aortic position, as
      mechanical valves are associated with lower physical capacity, a higher
      prevalence of disability, and poorer disease perception. Early surgical referral
      and atrial fibrillation surgery may improve survival after MVR.

PMID- 15740952
TI  - Aortic root abscess and secondary infective mitral valve disease: results of
      surgical endocarditis treatment.
AB  - OBJECTIVE: Mortality in active infective endocarditis (AIE) is substantial and
      reinfection can strongly influence outcome. Assessment of factors influencing
      mortality is important. We studied 108 (33%) patients suffering from root abscess
      out of a total of 327 AIE patients admitted to the Deutsches Herzzentrum Berlin
      for surgical treatment between 1996 and 2003. Among them were 53 (25.5% of all
      patients) who were diagnosed as having secondary infective mitral valve disease
      (SMVD). Mean age was 53+/-14.2 years; there were 37 men and 16 women. METHODS:
      Risk factors were assessed on the basis of clinical, hemodynamic,
      echocardiographic and surgical information. Mean follow-up was 325+/-251 days
      with complete echocardiographic examination performed in patients with double
      valve surgery. The differences between groups were analyzed using Student's t
      test. Multivariate analysis for the whole group suffering from abscess was
      performed to identify independent factors influencing mortality. RESULTS: In 19
      (35.8%) patients suffering from SMVD mitral valve reconstruction was undertaken
      and mitral valve replacement was performed in 34 (64.2%) patients. There were 27
      patients treated with a Shelhigh prosthesis: 18 with double valve replacement
      (both Shelhigh) and nine with an aortic Shelhigh prosthesis and concomitant
      mitral valve reconstruction. Homografts were used in 17 patients, with mitral
      reconstruction in 10 and a stented mitral prosthesis in seven. In nine cases two
      stented valve prostheses were used. The calculated mean Doppler gradient for
      homografts and Shelhigh in aortic position was 12 (+/-5.7) and 15 (+/-4.6),
      respectively (NS). The following predisposing factors for mortality were
      assessed: severe damage of aortic annulus (OR 4.65, CI 1.22-17.1, P=0.0159);
      septic shock (OR 3.44, CI 0.85-13.9, P=0.07) and poor ejection fraction (<40%),
      and dilated LV. CONCLUSIONS: Excessive mortality reaching 29% was noted in
      patients suffering from AIE with aortic ring abscess and SMVD requiring double
      valve surgery. Double valve surgery with semi-stented Dacron-free valve
      prostheses is associated with a low rate of reinfection and good function of the
      implants. The most potent independent risk factors for death were septic shock
      and severe aortic root destruction.

PMID- 15740953
TI  - Patient-prosthesis mismatch in aortic valve replacement: really tolerable?
AB  - OBJECTIVE: Several studies have demonstrated favorable results despite patient
      prosthesis mismatch after aortic valve replacement with the use of third
      generation prostheses. Our aim was to determine whether this mismatch is always
      tolerable. METHODS: A clinical-echocardiographic study has been performed in 339
      consecutive patients who underwent aortic valve replacement because of aortic
      stenosis. In-hospital outcome and left ventricular mass index regression (1st
      month-1st year) were analyzed in the presence or absence of mismatch (indexed
      effective orifice area < or =0.85cm(2)/m(2)). The influence of high degrees of
      preoperative left ventricular mass on in-hospital mortality has also been
      evaluated. Left ventricular mass index was considered increased if the calculated
      value was over the superior quartile of the frequency distribution of all the
      values observed in both sexes. RESULTS: Mismatch was found in 38% of the
      patients. In the absence of mismatch, the absolute mass regression was
      proportional to the preoperative left ventricular mass. This regression was
      higher in patients with increased left ventricular mass indexed (vs not
      increased): -38.0+/-7.8 vs -8.8+/-4.7g/m(2), p<0.01 (1st month) and -67.7+/
      16.9vs -23.5+/-6.7g/m(2), p<0.05 (1st year). Mass regression was impaired in the
      presence of mismatch, particularly, in patients with previously increased left
      ventricular mass: -8.2+/-11.6 vs -5.6+/-6.3g/m(2) (p=0.83) and -24.6+/-12.6 vs 
      11.7+/-10.5g/m(2) (p=0.54). This worse regression was reflected on a 100%
      incidence of residual hypertrophy at follow-up (1st month-1st year). In the
      presence of mismatch, increased ventricular mass was associated with higher
      mortality: 14.7% vs 2.1% (p<0.01). In the absence of mismatch, ventricular mass
      was not associated with mortality: 4.1 vs 2.5% (p=0.55). CONCLUSIONS: In patients
      with severe ventricular hypertrophy it may be important to elude patient
      prosthesis mismatch to avoid a significant increase in mortality and improve
      ventricular mass regression. Mismatch may be tolerable in those patients with
      lesser degree of hypertrophy.

PMID- 15740954
TI  - Characteristic resistance curves of aortic valve substitutes facilitate
      individualized decision for a particular type.
AB  - OBJECTIVE: Biological valves exhibit characteristic curves (CC) regarding
      transvalvular gradient, resistance, and effective orifice area when correlated
      with a physiological cardiac output range (CO). The slope of the curve of
      transvalvular resistance over a typical CO range characterizes the clinical
      performance of the valve. These information may support an individualized
      decision towards the most adequate valve type. METHODS: In an extracorporeal mock
      circuit two types of stented biological aortic valves (constructed pericardial
      valves, Edwards Perimount: EP; porcine cusp valves, Medtronic Mosaic: MM) of 21,
      23, and 25 mm were investigated. Mean transvalvular gradient was measured over a
      range of 1.9 to 7.2l/min CO at a simulated heart rate of 70 beats/min.
      Transvalvular resistance was calculated and presented as characteristic curves in
      a log-log-plot against cardiac output. RESULTS: EP valves of all sizes
      demonstrated low slopes (resistance range; slope: 21 mm: 53-79 dynes s cm(-5);
      0.29; 23 mm: 44-56 dynes s cm(-5); 0.12; 25 mm: 38-45 dynes s cm(-5); 0.12) while
      MM valves exhibited steep slopes (resistance range; slope: 21 mm: 46-169 dynes s
      cm(-5); 0.97; 23 mm: 36- -146 dynes s cm(-5); 0.95; 25 mm: 27-64 dynes s cm(-5);
      0.68). CONCLUSIONS: While constructed pericardial valves demonstrate sufficient
      hemodynamic performance especially in the higher CO range porcine cusp valves
      exhibited minor resistance in the lower CO range. Patients who exercise regularly
      may therefore profit from a pericardial valve while patients with a small body
      surface area and little exercise who therefore remain in the lower CO range may
      be adequately treated with a porcine cusp valve.

PMID- 15740955
TI  - Surgical treatment of atrial fibrillation with diathermy: an in vitro study.
AB  - OBJECTIVE: The utilization of diathermy (electrocautery) as an energy source in
      the treatment of chronic atrial fibrillation has generated positive early
      clinical results. Although this technology is available and affordable, it has
      not been well studied for this indication. The objectives of this study were: (1)
      to characterize atrial lesions created by diathermy, (2) to determine
      relationships between power setting, tissue contact time, and lesion depth and
      (3) to histologically compare diathermy and unipolar radiofrequency lesions.
      METHODS: Fresh bovine atrial tissue samples were used to create endocardial
      lesions using a unipolar diathermy system with a blade tip. A total of 120
      lesions were created at varying power settings and tissue contact times.
      Subendocardial temperatures were recorded. All lesions were examined grossly,
      then fixed, sectioned and evaluated histologically by a blinded pathologist.
      Comparisons were made with saline irrigated unipolar radiofrequency lesions.
      RESULTS: Gross examination revealed extensive tissue destruction of the
      endocardial surface at the point of contact. Histological examination showed
      minimal penetrance of the lesions beyond the destroyed tissue margin of the
      endocardium. This was corroborated by the finding of minimal thermal penetration
      beyond the endocardium and superficial myocardium. There was a linear
      relationship between the power setting (15-55 watts), depth of penetrance (2-15
      mm) at varying contact times (1-5s/cm). CONCLUSIONS: In this in vitro model,
      lesions created by diathermy were not transmural, even with high power settings
      and prolonged contact times. At these settings, significant tissue destruction
      was observed that may predispose to atrial perforation without achieving
      penetration. Diathermy did not constitute an effective energy source in the
      creation of transmural lesions for atrial fibrillation ablation.

PMID- 15740956
TI  - Accurate quantitation of regurgitant volume with MRI in patients selected for
      mitral valve repair.
AB  - OBJECTIVE: Echocardiography, the currently preferred diagnostic approach for
      mitral valve regurgitation, cannot accurately quantify the amount of
      regurgitation. Flow quantification with MRI is possible, but the conventional
      method (1-directional velocity-encoding) acquires the flow at a fixed location
      during the cardiac cycle, which is not necessarily the location of the mitral
      valve during the whole cycle. In this study, the exact flow through the mitral
      valve was quantified with a 3-directional velocity-encoded MRI approach. METHODS:
      Ten patients with severe mitral valve regurgitation (class 3-4+with
      echocardiography) resulting from systolic restrictive motion of both leaflets
      (Carpentier IIIb) which were selected for valve repair and 10 healthy volunteers
      without cardiac valvular disease confirmed with echocardiography were included in
      this study. The intra-ventricular flow was sampled with a radial stack of six
      acquisition planes parallel to the long-axis of the left ventricle. Three
      directional velocity-encoded MRI was performed resulting in the intra-ventricular
      flow velocity vector field for 30 phases during the cardiac cycle. The position
      of the mitral valvular plane in this vector field was indicated manually for each
      phase. Velocity values perpendicular to this plane determined the flow through
      the mitral valve. Both the 3-directional encoded mitral valve flow and the 1
      directional encoded mitral valve flow were compared with the flow determined with
      MRI at the ascending aorta. RESULTS: One-directional velocity-encoded MRI showed
      a mean overestimation (P<0.01) of 25 ml/cycle compared to the aortic flow.
      Correlation was very poor (r(P)=0.15, P=0.68). The 3-directional velocity-encoded
      MRI on the other hand, showed no over/underestimation and a good correlation
      (r(P)=0.91, P<0.01 for volunteers, r(P)=0.90, P<0.01 for patients). The
      regurgitant flow fractions were between 3 and 30%. CONCLUSION: With 3-directional
      velocity-encoded MRI, measurement of the flow through the mitral valve is
      accurate and reproducible. This is a valuable tool for diagnosing and absolute
      quantification of regurgitant volume.

PMID- 15740958
TI  - New technology and old responsibilities.

PMID- 15740957
TI  - Ventricular myocardial architecture as visualised in postmortem swine hearts
      using magnetic resonance diffusion tensor imaging.
AB  - OBJECTIVE: The three-dimensional arrangement of the ventricular myocardial
      architecture remains controversial, in part because histological assessment is
      difficult to achieve, while anatomic dissections are, of necessity, destructive.
      In this study, we describe how the use of magnetic resonance diffusion tensor
      imaging has permitted us to reconstruct with precision the architecture of the
      ventricular myocardial fibres in the post-mortem swine heart. METHODS AND
      RESULTS: We obtained diffusion-weighted spin-echo measurements of autopsied
      porcine hearts using a whole body MR system. We calculated the diffusion tensor
      and the corresponding eigenvectors on a voxel-by-voxel basis. This permitted us
      to colour code the fibres, and reconstruct them by connecting voxels in direction
      of the largest eigenvector. Such reconstructions show that, in the middle layer
      of the left ventricle, most of the fibres have a circular orientation, albeit
      that a far from negligible component runs in a transverse direction. With
      increasing distance from the epicardium, the orientation of the fibres shows a
      continuous change in angulation with respect to an axis normal to the epicardium.
      CONCLUSION: Our data presented here supports the concept that the ventricular
      mass is arranged as a complex three-dimensional mesh of tangential and intruding
      fibres. The data offers no support for the concept of a "unique myocardial band".
      The method has the potential to detecting deviations from this basic normal
      architecture, being capable of reconstructing the ventricular mass so as to
      assess the spatial coordinates of any single fibre strand. The technique,
      therefore, has major potential clinical applications in the setting of the
      failing or malformed heart, potentially being able to identify either systematic
      or regional disarray of the myocardial fibres.

PMID- 15740959
TI  - Left ventricular dimension and shape after postinfarction aneurysm repair.
AB  - OBJECTIVE: We evaluated left ventricular dimensions and shape in the patients
      with postinfarction LV aneurysm before and after different techniques of
      ventricular reconstruction. METHODS: From January 1997 to December 2003, 158
      patients underwent LV aneurysm repair. There were 152 men and 6 women, with a
      mean age 50+/-8.4 years. Ventricular reconstruction was performed by using linear
      plasty of the Cooley technique in 35 patients, septal plasty of the Stoney
      technique-in 57 patients, and endoventriculoplasty of the Dor technique-in 66
      patients. Left ventricular volumes and dimensions, global and contractile left
      ventricular function, diastolic sphericity were analyzed before and after
      operation over a period of 10 days to 5 years. RESULTS: The EchoCG studies showed
      a significant postoperative improvement of the LV contracting function regardless
      of LV plasty technique used. The index of sphericity changed from 0.71+/-0.08 to
      0.72+/-0.06 after linear plasty, from 0.71+/-0.05 to 0.73+/-0.07 after septal
      plasty, from 0.74+/-0.06 to 0.56+/-0.05 after endoventriculoplasty. The hospital
      mortality rate was 6.3%. There is no significant difference in hospital mortality
      rates between the different techniques of LV aneurysm repair. CONCLUSIONS: Our
      results show the effectiveness of different techniques of LV aneurysm repair,
      when the differentional approach to choice an adequate method of ventricular
      reconstruction was applied.

PMID- 15740960
TI  - Treatment of extensive ischemic cardiomyopathy: quality of life following two
      different surgical strategies.
AB  - OBJECTIVE: To review outcomes and quality of life following two surgical
      strategies for severe left ventricular dysfunction due to ischemic dilated
      cardiomyopathy. METHODS: Hospital and follow-up records of 111 patients with
      extensive ischemic cardiomyopathy (mean age 57.3+/-8.4) referring to our
      institution between January 1996 and December 2003 were reviewed. Group A
      included 42 patients (mean age 62.4+/-7.9) with morphological and functional
      cardiac parameters allowing for ventricular restoration (including
      endoventricular circular patch plasty, coronary artery by-pass grafting, and,
      when needed, mitral surgery). Group B included 69 patients (mean age 54.3+/-7.2),
      undergoing cardiac transplantation. Hospital mortality, treatment-related late
      mortality, incidence of cardiac events, freedom from cardiac failure, freedom
      from hospital re-admission, functional recovery at follow-up (3075.2pts/months;
      100% complete) and quality of life (WHOQOL test) were assessed. RESULTS: Hospital
      mortality was 19% in group A and 8.7% in group B (P=0.143). No treatment-related
      late deaths were observed in group A, while six deaths (9.5%) occurred in group B
      (P=0.063). Incidence of cardiac events was comparable. At 60 months, freedom from
      cardiac failure was 93.5+/-0.04 and 86.2+/-0.05%, respectively (P=0.23), freedom
      from hospital re-admission was 93.5+/-0.04 and 61.3+/-0.07% (P=0.002). Exertion
      dyspnea was present in 40% patients in group A versus 13% in group B (P=0.006).
      WHOQOL test showed a satisfying quality of life in both groups, although patients
      undergoing restoration reached higher scores in the psychological and social
      domains. CONCLUSIONS: Selected patients with ischemic cardiomyopathy, potentially
      eligible for transplantation, can be managed by ventricular restoration. In those
      patients post-operative quality of life is satisfactory, with comparable survival
      and low risk of re-hospitalization.

PMID- 15740961
TI  - Hemodynamics in off-pump surgery: normal versus compromised preoperative left
      ventricular function.
AB  - OBJECTIVE: Off-pump coronary surgery (OPCABG), avoiding cardiopulmonary bypass
      and cardioplegic arrest, seems to be a better choice in patients with poor
      baseline cardiac function. Since cardiocirculatory collapse could be induced by
      heart displacement in this group of patients at high risk, a greater
      pathophysiologic understanding of the hemodynamic derangements occurring in such
      patients is needed. METHODS: Twenty-eight elective OPCABG patients were evaluated
      for hemodynamic changes induced by heart displacement, using arterial
      thermodilution to measure cardiac output and global end-diastolic volume.
      Hemodynamic parameters were recorded: at baseline; during proper exposure and
      stabilization of each vessel; and at the end of surgery. Patients were divided
      into two groups, according to baseline ejection fraction (EF): group A (EF>30%;
      N=16), group B (EF< or =30%; N=12). RESULTS: Heart displacement induced a
      significant drop in the cardiac and stroke index, with a lesser decrease of mean
      arterial pressure because of raised systemic vascular resistance. Preload,
      measured as global end diastolic volume, significantly decreased in group A,
      while it remained unchanged or increased in group B. Linear regression between
      the preload index and left ventricular stroke work was significant only in group
      A. CONCLUSIONS: Patients with poor baseline cardiac function can well tolerate
      OPCABG. However, the pathophysiologic modifications underlying the hemodynamic
      changes are different compared to those in patients with good preoperative
      cardiac performance.

PMID- 15740962
TI  - Risk factors for hemorrhage-related reexploration and blood transfusion after
      conventional versus coronary revascularization without cardiopulmonary bypass.
AB  - OBJECTIVE: The premise of coronary revascularization without cardiopulmonary
      bypass (off-pump CABG) proposes that patient morbidity and, potentially,
      mortality can be reduced without compromising the excellent results of
      conventional revascularization techniques (on-pump CABG). It is unknown, however,
      whether coronary artery bypass without cardiopulmonary bypass (off-pump CABG) is
      associated with similar hemorrhage related reexploration rates and blood
      transfusion requirements compared to the on-pump approach. METHODS: Between
      January 1998 and June 2002, 3646 patients underwent off-pump CABG and were
      compared with a contemporaneous control group of 5197 on-pump CABG patients. A
      logistic regression model was used to test the difference in the postoperative
      hemorrhage related reexploration rates and need for postoperative blood
      transfusions between the groups, controlling for preoperative risk factors. The
      patients undergoing off-pump CABG were matched to on-pump patients by propensity
      score. RESULTS: Hemorrhage related reexploration rates were comparable between
      the 2 groups (odds-ratio [OR]=0.80, 95% confidence intervals [CI]=0.55-1.09,
      P=0.15). Off-pump CABG was associated with a lower need for single and multiple
      unit postoperative blood transfusions (OR=0.30, CI=0.24-0.31, P<0.01 and OR=0.4,
      CI=0.36-0.51, P<0.01, respectively) compared to on-pump CABG patients.
      CONCLUSIONS: Off-pump CABG eliminates the risks of cardiopulmonary bypass and the
      systemic inflammatory response it elicits. A substantially lower need for
      postoperative blood transfusions and a comparable hemorrhage-related
      reexploration rate suggests that off-pump CABG may avoid the morbidity and
      mortality associated with excessive postoperative blood loss.

PMID- 15740963
TI  - Pharmacological preconditioning with monophosphoryl lipid A improves post
      ischemic diastolic function and modifies TNF-alpha synthesis.
AB  - OBJECTIVE: Pharmacologic preconditioning represents an attractive myocardial
      protection strategy. Tumor necrosis factor-alpha plays an important role in
      myocardial ischemia-reperfusion injury. We aimed to determine the effect of
      Monophosphoryl lipid A-induced delayed preconditioning on diastolic and systolic
      left ventricular function and tumor necrosis factor-alpha synthesis during
      ischemia and reperfusion. METHODS: Rats (n=10) were pretreated with
      Monophosphoryl lipid A (350 microg/kg) or vehicle (n=9). Twenty-four hours later,
      the hearts were isolated and perfused on a Langendorff apparatus. Hemodynamic
      measurements, tumor necrosis factor-alpha mRNA expression and protein content
      were studied after stabilization (baseline), after 35 min of global ischemia and
      at 40 min of reperfusion. RESULTS: Left ventricular developed pressure and peak
      rate of left ventricular developed pressure (dP/dt) rise were comparable between
      the animals in the control and Monophosphoryl lipid A treated groups during
      baseline but were higher in Monophosphoryl lipid A group at reperfusion (74+/-4
      vs 51+/-5 mmHg, 3340+/-172 vs 2240+/-156 mmHg/s, respectively, P<0.01). dP/dt
      fall was significantly lower in the MLA group (2630+/-225v 1580+/-210 mmHg/s,
      P<0.01) at 40 min of reperfusion as well as end diastolic pressure. Baseline
      tumor necrosis factor-alpha mRNA (expressed as arbitrary densitometry units) were
      higher in the Monophosphoryl lipid A group (1.3+/-0.1 vs 0.5+/-0.03, P<0.05) but
      remained constant after ischemia and reperfusion (1.3+/-0.1 and 1.4+/-0.03,
      P=0.2), while further increase was observed in the control group (from 1.0+/-0.1
      to 1.4+/-0.1, P<0.05). Tumor necrosis factor-alpha protein content from heart
      effluent in the control group was increased during reperfusion (79+/-30 and 200+/
      22pg/ml, P<0.05) but was undetectable in the Monophosphoryl lipid A group. Marked
      TNF-alpha immunostaining of left ventricular tissue was observed only in the
      control group but no TNF-alpha staining was evident in the Monophosphoryl lipid A
      treated group at 40 min of reperfusion. CONCLUSION: Monophosphoryl lipid A
      induced preconditioning renders the heart more tolerant to ischemia-reperfusion
      in terms of left ventricular diastolic and systolic function, and prevents tumor
      necrosis factor-alpha production during ischemia, through aborting the
      translation phase of tumor necrosis factor-alpha synthesis.

PMID- 15740965
TI  - Left main coronary artery compression in chronic thromboembolic pulmonary
      hypertension.

PMID- 15740964
TI  - The predictors and outcome of recidivism in cardiac ICUs.
AB  - OBJECTIVE: Reinstitution of step-up care (recidivism) following cardiac surgery
      may be associated with increased mortality. This has, however, not been widely
      reported. METHODS: We, therefore, studied 8113 consecutive patients who underwent
      coronary artery bypass grafting (CABG), valve replacement/repair or combined
      valve+CABG surgery between January 1996 and December 2003 to determine the
      reasons for readmission to the intensive care unit (ICU) and their outcomes in
      terms of length of stay in (i) the ICU (ii) hospital and (iii) the in-hospital
      mortality following recidivism. RESULTS: Of the 7717 patients discharged out of
      the ICU, 2.3% (182) of patients [mean age 70.4+/-8.35 years (range 30-90 years);
      65.4% (119) males] required step-up care. Recidivism was 1.8% (101 of 5633)
      following coronary artery by-pass grafting (CABG) and 3.9% (81 of 2084) following
      valve replacement/repair+/-CABG (P<0.05). The mean interval from ICU discharge to
      ICU recidivism was 6.6+/-8.4 days (range 6h to 28 days). The principal reasons
      for recidivism were (i) respiratory failure requiring reintubation and
      ventilation in 54.9% (n=100) of patients (ii) cardiovascular instability
      (including that secondary to dysrhythmias) and heart failure in 23.1% (n=42)
      (iii) renal failure requiring haemofiltration in 6.6% (n=12) (iv) sepsis in 1.1%
      (n=2) (v) cardiac tamponade/bleeding requiring re-exploration in 7.7% (n=14) and
      (vi) gastro-intestinal complications requiring laparotomy in 6.0% (n=11)
      patients. Multivariate analysis showed that, during primary ICU stay, respiratory
      complications, low cardiac output state, dysrhythmias, renal failure requiring
      haemofiltration and re-exploration for bleeding were independent predictors of
      recidivism. Following recidivism (i) the mean length of stay in the ICU was
      6.65+/-6.2 days (range 4h to 51 days), (ii) mean hospital stay was 19.2+/-17.3
      days (10-60 days) and (iii) the 30-day in-hospital mortality was 32.4%.
      CONCLUSIONS: Patients are more likely to require recidivism following valve
      surgery+/-CABG than CABG alone. Whilst respiratory complications were the most
      common reasons for recidivism in our study, patients who required mechanical
      supports to maintain vital functions following surgery were most prone to
      recidivism. Hence, efforts should be made to treat cardio-respiratory problems
      early in this group of patients to reduce ICU recidivism.

PMID- 15740966
TI  - Coexisting fibrous dysplasia and bone cyst of a rib after labour trauma.

PMID- 15740967
TI  - Acquired chest wall deformity: huge axillary lipoma.

PMID- 15740968
TI  - Left subclavian artery free graft as a salvage technique after failed coronary
      artery transfer in arterial switch operation.
AB  - Coronary artery transfer in transposition of the great arteries with single
      coronary artery or intramural coronary artery is still a technically demanding
      procedure. We present a technique of left coronary bypass using a free graft of
      left subclavian artery for the management of failed coronary artery transfer of
      left intramural coronary artery.

PMID- 15740969
TI  - Unusual presentation of myocardial ischemia after arterial switch operation.
AB  - Ischemic changes and acute or subacute cardiac failure after arterial switch
      operation generally results from imperfect transfer of coronary arteries to the
      neoaorta. Peroperative and early postoperative myocardial ischemia is the main
      cause of death in these patients. We present an unusual cause of myocardial
      ischemia and cardiac failure after arterial switch: a congenital coronary artery
      fistula between the circumflex artery and the right ventricle. The symptoms
      imitate coronary translocation failure. In differential diagnosis of the coronary
      perfusion problems encountered after the arterial switch operation, coronary
      artery fistula should not be forgotten, although it is rare.

PMID- 15740970
TI  - Late thoracic aortic dissecting aneurysm following balloon angioplasty for
      recoarctation after subclavian flap aortoplasty in childhood--successful surgical
      repair under circulatory arrest.
AB  - Balloon angioplasty is universally accepted presently as the primary therapeutic
      strategy for recoarctation following surgery during infancy and early childhood.
      This report concerns a 26-year-old lady with cephalobrachial hypertension on beta
      blocker who presented with left sided chest pain since 3 months, having undergone
      surgery for coarctation in early childhood and balloon angioplasty at 17 years of
      age. Chest X-ray showed prominent aortic knuckle. CT scan chest showed features
      of residual coarctation with "double-barrelled" upper thoracic aorta of 5cm
      diameter. Surgery consisted of interposition graft repair of distal arch and
      upper thoracic aorta under total circulatory arrest through posterolateral
      thoracotomy leading to excellent recovery.

PMID- 15740971
TI  - Bluntly traumatic tracheal transection: usefulness of percutaneous
      cardiopulmonary support for maintenance of gas exchange.
AB  - Respiratory management of tracheal injuries is a crucial key to successful
      treatment. We present herein a patient with a traumatic tracheal transection in
      whom we confronted difficulty in airway management after false intratracheal
      intubation. No associated injuries were seen in the patient, then, primary repair
      of the trachea was carried out under ventilatory support via percutaneous
      cardiopulmonary support system (PCPS). For a short period in the application of
      PCPS, the use of a heparin-coated circuit made systemic heparinization
      unnecessary during and after operation, and the outcome was satisfactory. In a
      carefully selected patient, ventilatory support via PCPS is useful.

PMID- 15740972
TI  - Perforation of the lower thoracic oesophagus following crush injury to the chest
      and abdomen.
AB  - We report a case of perforation of the lower thoracic oesophagus following a
      crush injury to the chest and upper abdomen. A laparotomy was performed for
      abdominal injuries, and appropriately placed drains resulted in complete
      resolution of the oesophageal leak, 21 days following the injury. This case
      report demonstrates that a conservative approach to lower thoracic oesophageal
      perforations can be carried out successfully without the added morbidity of a
      thoracotomy, or risks of a direct repair.

PMID- 15740974
TI  - Vasomotor dysfunction after cardiac surgery; another look.

PMID- 15740976
TI  - CABG in obese patient: is the degree of obesity the key factor?

PMID- 15740977
TI  - Embolisation, inflammatory reaction and persistent patent false lumen: is
      biological glue really effective in repair of type A aortic dissection?

PMID- 15740979
TI  - 1400W, a potent selective inducible NOS inhibitor, improves histopathological
      outcome following traumatic brain injury in rats.
AB  - There are conflicting data regarding the role of nitric oxide (NO) produced by
      inducible NO synthase (iNOS) in the pathophysiology of traumatic brain injury
      (TBI). In this report, we evaluated the effect of a potent selective (iNOS)
      inhibitor, 1400W, on histopathological outcome following TBI in a rat model of
      lateral fluid percussion brain injury. First, to design an appropriate treatment
      protocol, the parallel time courses of iNOS and neuronal NOS (nNOS) gene
      expression, protein synthesis, and activity were investigated. Early induction of
      iNOS gene was observed in the cortex of injured rats, from 6 to 72 h with a peak
      at 24 h. Similarly, iNOS protein was detected from 24 to 72 h and de novo
      synthesized iNOS was functionally active, as measured by Ca2+-independent NOS
      activity. The kinetic studies of nNOS showed discrepancies, since nNOS gene
      expression and protein synthesis were constant in the cortex of injured rats from
      24 to 72 h, while Ca2+-dependent constitutive NOS activity was markedly decreased
      at 24 h, persisting up to 72 h. Second, treatment with 1400W, started as a bolus
      of 20 mg kg-1 (s.c.) at 18 h post-TBI, followed by s.c.-infusion at a rate of 2.2
      mg kg-1 h-1 between 18 and 72 h, reduced by 64% the brain lesion volume at 72 h.
      However, the same treatment paradigm initiated 24 h post-TBI did not have any
      effect. In conclusion, administration of a selective iNOS inhibitor, 1400W, even
      delayed by 18 h improves histopathological outcome supporting a detrimental role
      for iNOS induction after TBI.

PMID- 15740980
TI  - Super-induction of HO-1 in macrophages stimulated with lipopolysaccharide by
      prior depletion of glutathione decreases iNOS expression and NO production.
AB  - In the LPS-stimulated macrophages undergoing oxidative burst, intracellular
      storage of glutathione (GSH) is depleted, expression of iNOS is enhanced, and NO
      is overproduced. In response to the depletion of GSH, expression of HO-1 is
      induced and HO activity is elevated. Thus, in macrophages treated with LPS,
      productions of NO and CO, catalyzed, respectively, by accumulated iNOS and HO-1,
      are increased in sequence [Biochem. Pharmacol. 68 (2004) 1709]. In support of
      this, HO-1 is induced in macrophages treated only with buthionine sulfoximine
      (BSO), an inhibitor of GSH biosynthesis depleting the GSH level. Alternatively,
      when the macrophages were exposed to spermine NONOate, an exogenous NO-donor, HO
      1, was induced also. When the GSH-depleted or BSO-pretreated macrophages were
      exposed to NO, delivered either exogenously from spermine NONOate or endogenously
      from LPS-derived elevation of iNOS, super-induction of HO-1 was observed.
      Moreover, both the BSO and LPS treatments increased the accumulation of HO-1
      inducing redox-sensitive transcription factor Nrf2 in the nuclear protein
      fraction. Thus, when the depletion of GSH is combined with NO delivery,
      expression of HO-1 is enhanced to a greater extent than that enhanced either by
      GSH depletion or by NO delivery. In these macrophages with super-induced HO-1 and
      elevated HO activity, LPS-derived increase in iNOS expression was down-regulated
      and NO production was suppressed. This indicated that induction of HO-1 caused by
      the NO overproduced from up-regulated iNOS, in turn, produces a causative
      inhibition on iNOS expression and NO production. Thus, it appears that there is a
      reciprocal cross-talk between inductions of HO-1 and iNOS in macrophages
      stimulated with LPS leading to their survival.

PMID- 15740981
TI  - Local and systemic expression of inducible nitric oxide synthase in comparison
      with that of cyclooxygenase-2 in rat carrageenin-induced pleurisy.
AB  - Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)
      is up-regulated in response to inflammatory stimuli. To evaluate the extent to
      which local pleural inflammation involves additional site in the pleural cavity
      and elsewhere, we investigated the time course of the levels of iNOS and its
      product in the inflammatory and other sites, and compared those with a level of
      COX-2 in rat carrageenin-induced pleurisy. The exudate and plasma NOx levels
      rose, reaching peaks at 9 and 14 h, respectively. Both COX-2 and iNOS became
      detectable in exudate leukocytes, their levels reaching peaks at 3 and 9 h after
      irritation, respectively. COX-2 was detectable mainly in neutrophils, but iNOS
      was detectable in both neutrophils and mononuclear leukocytes. Furthermore, iNOS
      became detectable in neutrophils and mononuclear leukocytes in enlarged
      parathymic lymph nodes from 3h in addition to those in peripheral blood and
      Kupffer cells from 3 to 14 h, respectively. The gene product is also detectable
      in thymic large dendritic cells of pleurisy-induced rats as well as normal
      control rats. COX-2 became detectable in stellar dendritic cells of the enlarged
      draining lymph nodes from 14 h. Thus, these gene products were induced in the
      immediate proximity of regional lymph nodes, and even at a considerable distance
      of liver by the local inflammatory stimulus. Although their expression pattern
      was quite different from each other, these gene products were detectable in
      phagocytic cells.

PMID- 15740982
TI  - Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO
      production.
AB  - At low energy density (0.03 mJ/mm2), extracorporeal shock waves (ESW), originally
      developed for clinical lithotripsy, have successfully been used for anti
      inflammatory treatment of soft tissues. Since nitric oxide plays a critical role
      in inflammation, we hypothesized for ESW to increase NO production in cells.
      Using human umbilical vein endothelial cells as a model system, we observed that
      ESW, at low energy density, rapidly induced an enhancement of eNOS activity. In
      these cells, eNOS activity is modulated by tyrosine- and serine-phosphorylation.
      ESW shifted eNOS to a less-tyrosine-phosphorylated form, without affecting its
      serine-phosphorylation, thus accounting for its rapid enzyme activation. LPS/IFN
      gamma treatment of human umbilical vein endothelial cells induced a rapid
      inhibition of eNOS activity and concomitant NF-kappaB activation which were
      efficiently counteracted by ESW treatment. Therefore, the present results
      indicate that the molecular mechanism of clinically observed anti-inflammatory
      action of ESW should include tyrosine-dephosphorylation of eNOS, a successive
      increase in NO production and suppression of NF-kappaB activation.

PMID- 15740983
TI  - A blend of polyphenolic compounds explains the stimulatory effect of red wine on
      human endothelial NO synthase.
AB  - A high intake of polyphenolic compounds is likely to have beneficial effects on
      the cardiovascular system. Especially red wine is a rich source of polyphenols,
      and we have previously shown that French red wine upregulates eNOS, a protective
      enzyme in the cardiovascular system. The current study tested (poly)phenolic
      constituents of red wine for their ability to enhance eNOS expression (and the
      activity of a 3.5-kb human eNOS promoter) in human EA.hy 926 endothelial cells.
      Of the compounds tested, we found 3,4',5-trihydroxy-trans-stilbene (trans
      resveratrol) to be the most efficacious stimulator of eNOS expression (and eNOS
      transcription), but this compound alone could not explain the total stimulatory
      effect of red wine. The flavanols catechin and epicatechin, the flavonols
      fisetin, myricetin, isoquercitrin and hyperoside, the anthocyanins delphinidin,
      malvidin, and paeonidin, gallic acid, and the hydroxycinnamic acids ferulic acid
      and sinapinic acid did not change eNOS expression or eNOS promoter activity in
      any substantial way. The flavonol quercetin inhibited eNOS expression (with no
      effect on eNOS promoter activity). Cinnamic acid was a rather potent enhancer of
      eNOS expression, however with an efficacy of only 170%. Surprisingly, it reduced
      eNOS promoter activity. The anthocyanins cyanidin, the hydroxycinnamic acids p
      coumaric acid and caffeic acid, and the phenolic acids benzoic acid and vanillic
      acid also enhanced eNOS expression moderately (with no effect on eNOS promoter
      activity). Thus, the increase in eNOS in response to red wine involves several
      polyphenolic compounds with a major contribution from trans-resveratrol and
      lesser contributions from cinnamic and hydroxycinnamic acids, cyanidin, and some
      phenolic acids.

PMID- 15740984
TI  - Ca2+-sensitivity and cGMP-independent effects of NO in vascular smooth muscle.
AB  - The effects of NO on Ca2+-sensitivity of vascular smooth muscle (VSM)
      myofilaments have been the focus of this study. Simultaneous measurements of
      [Ca2+]i and force were carried out in rat tail artery segments. NO, 10(-7) M,
      evoked a transient decrease in [Ca2+]i accompanied by sustained relaxation
      (45.3+/-6.3 vs. 69.45+/-7.2%, P<0.05, respectively) of VSM precontracted with K+
      (70 mM), suggesting a decrease in Ca2+-sensitivity of VSM. This decrease in Ca2+
      sensitivity was completely abolished by preincubation of VSM with ODQ (10(-6) M)
      (63.9+/-7.8% for [Ca2+]i vs. 20.5+/-8.4% for relaxation, P<0.05). Ca2+
      presensitization of VSM myofilaments with PE (10(-6) M) decreased the efficacy of
      NO to relax VSM (44.25+/-6.9% vs. 69.45+/-7.2%, P<0.05), but increased its
      ability to lower [Ca2+]i (70.5+/-6.8% vs. 45.3+/-6.3%, P<0.05). Application of
      DTT (10(-3) M) together with ODQ (10(-6) M) to subtract possible cGMP-independent
      effects revealed the total suppression of both the relaxant responses and [Ca2+]i
      of VSM under high-K+ preactivation of VSM. The data indicate that NO not only
      relaxes VSM and lowers [Ca2+]i in K+-preactivated VSM, but also decreases Ca2+
      sensitivity of VSM myofilaments and these effects are strongly cGMP-dependent. In
      PE-induced contractions of VSM, NO relaxed VSM of rat tail artery and lowered
      [Ca2+]i, but failed to reverse Ca2+-presensitized myofilaments. We suggest that
      alternative cGMP-independent effects of NO are primarily manifested via
      activation of K+-channels and inhibition of Ca2+ current rather than to affect
      relaxation. An importance of reduced SH-groups within VSM myoplasm for both
      relaxation and [Ca2+]i disposal evoked by NO is evident whatever Ca2+
      mobilization pathways are involved.

PMID- 15740985
TI  - The nitric oxide prodrug, V-PYRRO/NO, protects against cadmium toxicity and
      apoptosis at the cellular level.
AB  - The liver is an important target tissue of cadmium. The compound O2-vinyl 1
      (pyrrolidin-1-yl)diazen-1-ium-1,2 diolate (V-PYRRO/NO) is a liver-selective
      nitric oxide (NO) prodrug that is metabolized by hepatic P450 enzymes to release
      NO in hepatocytes. In vivo, V-PYRRO/NO can protect against the toxicity of
      various hepatotoxicants, including cadmium. Since NO is an effective vasodilator,
      whether this protective effect against cadmium toxicity is at the level of the
      hepatic vascular system or actually within the liver cells has not been defined.
      Thus, we studied the effects of V-PYRRO/NO pretreatment on cadmium-induced
      toxicity and apoptosis in cultured rat liver epithelial (TRL 1215) cells. Cells
      were pretreated with V-PYRRO/NO at 500 or 1000 microM for up to 24 h, then
      exposed to cadmium (as CdCl2) for additional 24 h and cytotoxicity was measured.
      Cadmium was significantly less cytotoxic in V-PYRRO/NO (1000 microM) pretreated
      cells (LC50=6.1+/-0.6 microM) compared to control cells (LC50=3.5+/-0.4 microM).
      TRL 1215 cells acted upon the prodrug to release NO, producing nitrite levels in
      the extracellular media after 24 h of exposure to 500 or 1000 microM V-PYRRO/NO
      measured at 87.0+/-4.2 and 324+/-14.8 microM, respectively, compared to basal
      levels of 7.70+/-0.46 microM. V-PYRRO/NO alone produced small increases in
      metallothionein (MT), a metal-binding protein associated with cadmium tolerance.
      However, V-PYRRO/NO pretreatment greatly enhanced cadmium induction of MT. V
      PYRRO/NO pretreatment also markedly reduced apoptotic cell death induced by
      cadmium (5 microM), apparently by blocking cadmium-induced activation of the c
      Jun N-terminal kinase (JNK) pathway. Thus, the prodrug, V-PYRRO/NO, protects
      against the adverse effects of cadmium directly within rat liver cells apparently
      through generation of NO and, at least in part, by facilitation of cadmium
      induced MT synthesis.

PMID- 15740986
TI  - Identification of S-nitrosylated proteins in endotoxin-stimulated RAW264.7 murine
      macrophages.
AB  - Nitric oxide (NO) is an omnipresent regulator of cell function in a variety of
      physiologic and pathophysiologic states. In part, NO exerts its actions by S
      nitrosylation of target thiols, primarily in cysteine residues. Delineating the
      functional correlates of S-nitrosylation can begin with identification of the
      entire population of S-nitrososylated proteins. Recently, the biotin switch
      technique was developed to allow a proteomic approach to identification of the
      "universe" of S-nitrsoylated proteins. In this study using endotoxin-stimulated
      RAW264.7 murine macrophages, we have utilized the biotin-switch technique and
      protein sequencing to identify S-nitrosylated proteins in this setting. In
      contrast to other studies utilizing exogenous sources of NO, our approach
      utilizes endogenous NO synthesis as the basis for S-nitrosylation. Our results
      indicate multiple unique proteins not previously identified as S-nitrosylation
      targets: enolase, pyruvate kinase, elongation factor-1 and -2, plastin-2, FRAG-6,
      CEM-16, and SMC-6. While the ubiquitous nature of NO argues for some degrees of
      commonality, S-nitrosylation of unique proteins specific to endotoxin stimulated
      macrophages suggests regulatory mechanisms for which NO is necessary, but not
      sufficient.

PMID- 15740987
TI  - Genome-wide scan of homogeneous subtypes of NIMH genetics initiative
      schizophrenia families.
AB  - In the light of the potential etiological heterogeneity of schizophrenia, we
      reanalyzed the NIMH genetics initiative data for schizophrenia. We performed
      linkage analyses on schizophrenia families divided into more homogeneous
      subgroups. The African-American and European-American families were divided into
      groups that were successively more homogeneous. The first group included
      schizophrenia families that were highly familial, meaning that they contained a
      minimum specified number of affected individuals. We also excluded patients with
      environmental influences that may affect disease status. These influences
      included obstetric complications (OC) and viral infections during the
      neurodevelopmental stage (VIN). In the African-American sample, a linkage
      analysis of highly familial schizophrenia families without any environmental
      influences resulted in a single-point LOD (SLOD) score of 2.90, a multipoint LOD
      (MLOD) of 2.11, a single-point heterogeneity LOD (SHLOD) score of 3.04, and a
      multipoint heterogeneity LOD (MHLOD) score of 2.11 at marker D8S1819 (8p23.1)
      under a dominant parametric model. The highly familial European-American
      schizophrenia families resulted in an SLOD of 0.91 and an MLOD of 1.85, an SHLOD
      of 1.64 and an MHLOD of 1.97 at marker D22S1169 (22q13.32) using a recessive
      parametric model. Although this work should be interpreted cautiously and
      requires replication, these results suggest that schizophrenia may be linked to
      chromosomal regions 8p23.1 and 22q12.3-q13.32.

PMID- 15740988
TI  - Cholecystokinin (CCK) and the CCKA receptor gene polymorphism, and smoking
      behavior.
AB  - We analyzed genetic variants of the promoter region of the cholecystokinin (CCK;
      which modulates the release of dopamine) gene, and intron 1 and exon 5 of the
      CCKA receptor gene, and performed association analyses of nicotine dependence
      using an allele-specific amplification (ASA) method and PCR-RFLP methods. There
      was a significant difference between the current smoking and nonsmoking groups in
      the allele frequency of the CCK-45C/T polymorphism. However, there was no
      significant difference in the CCKA PstI polymorphism, and the HincII polymorphism
      was not detected in our study. Our data suggest that polymorphisms of the CCK
      gene may be one of the risk factors for smoking behavior.

PMID- 15740989
TI  - A comparison of electronic monitoring vs. clinician rating of antipsychotic
      adherence in outpatients with schizophrenia.
AB  - Antipsychotic non-adherence rates of outpatients with schizophrenia or
      schizoaffective disorder was assessed by electronic monitoring and clinician
      rating. Antipsychotic adherence was determined monthly over 3 consecutive months
      with (1) the Medication Event Monitoring System (MEMS) cap and (2) the Clinician
      Rating Scale. Non-adherence was defined as daily adherence of <70% during any one
      of three monthly evaluations for MEMS and ratings of <or=4 (scale of 1-7) on the
      Clinician Rating Scale. Non-adherence was detected in 12 of 25 patients (48%) by
      MEMS and 0% by the Clinician Rating Scale. Clinician assessment dramatically
      underestimated antipsychotic non-adherence.

PMID- 15740990
TI  - Emotion recognition, 'theory of mind,' and social behavior in schizophrenia.
AB  - Several studies have demonstrated that patients with schizophrenia are impaired
      in recognizing emotions from facial expressions and in appreciating other
      people's mental states--the latter commonly referred to as 'theory of mind.' The
      question as to how social cognitive skills relate to patients' actual social
      behavior is, however, largely unanswered. This study examined emotion
      recognition, 'theory of mind,' and social behavior in schizophrenia. Emotion
      recognition, 'theory of mind,' executive functioning, 'crystallized' verbal
      intelligence, psychopathology, and social behavior were assessed in patients with
      schizophrenia compared with a healthy control group. Patients were significantly
      impaired on all tasks involving executive functioning, emotion recognition, and
      'theory of mind.' Impaired executive functioning did, however, only partially
      account for the deficits in social perception and social cognition. Social
      perception and cognition in schizophrenia predicted the odds of being a patient
      significantly better than nonsocial cognition. Severe social behavioral
      abnormalities were linked to the duration of the illness, and even more so to
      'theory of mind' deficits. Considering impaired social perception and social
      cognition significantly contributes to the understanding of social behavioral
      problems in schizophrenia.

PMID- 15740991
TI  - Effects of emotion and identity on facial affect processing in schizophrenia.
AB  - We used facial affect labeling and matching tasks to study effects of (1) emotion
      and (2) identity on facial affect processing in patients with remitted
      schizophrenia (n=30) compared with healthy controls (n=30). The patients (1) had
      a specific deficit for labeling facial affects of sadness and anger but not
      happiness, disgust and fear; they (2) performed as well as controls in matching
      facial affects in one face but were impaired in matching facial affects in two
      different faces. The patients' impairment in facial affect processing may be
      emotion-specific. The effects of identity on facial affect processing are
      discussed in the light of several hypotheses (a deficit of context processing, a
      global-local processing impairment or a selective attention deficit), and may be
      related to frontal, prefrontal or amygdala dysfunctions.

PMID- 15740992
TI  - Dynamical quantification of schizophrenic speech.
AB  - Schizophrenic speech has been studied both at the clinical and linguistic level.
      Nevertheless, the statistical methods used in these studies do not specifically
      take into account the dynamical aspects of language. In the present study, we
      quantify the dynamical properties of linguistic production in schizophrenic and
      control subjects. Subjects' recall of a short story was encoded according to the
      succession of macro- and micro-propositions, and symbolic dynamical methods were
      used to analyze these data. Our results show the presence of a significant
      temporal organization in subjects' speech. Taking this structure into account, we
      show that schizophrenics connect micro-propositions significantly more often than
      controls. This impairment in accessing language at the highest level supports the
      hypothesis of a deficit in maintaining a discourse plan in schizophrenia.

PMID- 15740993
TI  - Saccadic performance in questionnaire-identified schizotypes over time.
AB  - In the present study, 121 young adults (mean age=19 years), hypothesized to be at
      varying levels of risk for psychosis on the basis of their psychometric profiles,
      were administered saccadic (antisaccade and refixation) tasks at two separate
      assessments. At Time 1, individuals posited to be at heightened risk for the
      later development of schizophrenia-spectrum disorders (i.e., those individuals
      with elevated Social Anhedonia Scale [SAS] scores) produced significantly more
      antisaccade task errors than the controls. Despite apparent improvement in
      antisaccade task performance from initial testing to the follow-up (mean test
      retest interval=59 months) across all groups, the Social Anhedonia (SocAnh) group
      continued to produce significantly more errors than the control group. The
      antisaccade task performance of the control group showed good temporal stability
      (Pearson's r=0.70, ICC=0.52), and the SocAnh group's performance showed excellent
      temporal stability (Pearson's r=0.85, ICC=0.83). The results of this
      investigation are twofold: First, antisaccade task performance is temporally
      stable, even in psychometrically identified schizotypes over long test-retest
      intervals; and secondly, Social Anhedonia Scale scores as well as Time 1
      antisaccade task accuracy accounted for much of the variability in Time 2
      antisaccade task performance. These findings add to the growing body of
      literature suggesting that antisaccade task deficits may serve as an
      endophenotypic marker of a schizophrenia diathesis.

PMID- 15740994
TI  - Do all people with schizophrenia receive the same benefit from different family
      intervention programs?
AB  - The study evaluated baseline characteristics that could be used to predict the
      outcome of family intervention in schizophrenia and focussed on identifying the
      subgroups of patients who were more likely to respond to one therapeutic modality
      than another. We conducted a controlled trial in which participants were assigned
      at random to either a Behavioral Family Intervention Group or a Relatives' Group.
      Patients in one catchment area, having suffered one psychotic relapse within the
      previous year and living with their families, were assessed by an independent
      evaluator at baseline and 12 months later. Some clinical and family factors such
      as the duration of illness, number of hospital admissions and relatives' level of
      psychological distress can predict the differential outcome of either type of
      family intervention modality. The results suggested that the short-term illness
      group requires more intensive and personal intervention, while the long-term
      illness group needs more continuous support. Our results should be confirmed in a
      larger sample before clinical recommendations can be made.

PMID- 15740995
TI  - Cholesterol-lowering therapy evokes time-limited changes in serotonergic
      transmission.
AB  - A number of studies have reported an increased risk for violent deaths and
      depression in subjects with reduced serum cholesterol concentrations. Links with
      hypothesized impairment of serotonin neurotransmission have not been
      satisfactorily tested. In this investigation, the serum and membrane cholesterol,
      microviscosity of erythrocyte membranes, platelet serotonin uptake, and clinical
      parameters were determined during pharmacotherapy of 17 hypercholesterolemic
      patients. A significant decrease in serum cholesterol and a nonsignificant
      decrease in membrane cholesterol concentration were found after 2 months of
      simvastatin therapy. Serotonin transporter (SERT) activity was significantly
      increased following 1 month of simvastatin; the tendency to decrease the initial
      increase in SERT activity was evident following 2 months of therapy. Both
      membrane cholesterol and SERT activity returned to pre-treatment levels after
      more than 1 year of therapy. Microviscosity of plasma membranes, impulsivity,
      empathy, adventure, sensation seeking, and depressed mood were not markedly
      changed. These data indicate that long-term therapy has different effects on
      serotonin transmission from short-term (1- to 2-month) therapy. A significant
      increase in SERT activity was detected only during the first month of simvastatin
      therapy. This finding suggests that within this period some patients could be
      vulnerable to depression, violence, or suicide.

PMID- 15740996
TI  - Suicides in the midnight sun--a study of seasonality in suicides in West
      Greenland.
AB  - Greenland is the most extreme of human habitats in regard to annual changes in
      natural light. From being very low, the rate of suicides in Greenland has
      increased during the past few decades to be among the highest in the world.
      Several studies have shown seasonality in suicides with spring or summer peaks,
      but this has not been previously shown in Greenland. Official data from 1968 to
      1995 from West Greenland were pooled. A significant seasonality in the 833
      suicides was found using Rayleigh's test, a peak in June and a trough in the
      winter. Suicides increased during the period, and reached high rates in most age
      groups, up to 577 per 100,000 person-years in men aged 15-24 years in 1990, and
      up to 147 per 100,000 person-years in women aged 15-24 years in 1995. Violent
      methods of suicide were used by 93%. Depression has been reported uncommonly.
      High alcohol intake and extended periods of light in the summer may contribute to
      impulsive-aggressive summer suicides.

PMID- 15740997
TI  - Auditory P3 indexes personality traits and cognitive function in healthy men and
      women.
AB  - The relationship of the auditory P3 event-related potential to major personality
      dimensions and neuropsychological performance was examined in psychiatrically
      healthy men and women (28 male, 15 female) recruited from the community. An
      auditory oddball paradigm was used to collect P3 amplitude and latency data.
      Personality traits were measured with the NEO Five-Factor Inventory. Several
      Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the Digit Symbol
      Test, and the Trail Making Test comprised the neuropsychological tests. A
      multivariate statistical procedure (Partial Least Squares) was used to quantify
      the relationships between P3 variables and personality and neuropsychological
      performance variables. P3 amplitude was negatively related to Neuroticism and
      positively related to Extraversion, Openness, Agreeableness and
      Conscientiousness. Better neuropsychological performance was associated with
      greater P3 amplitude and earlier latency. Thus, greater P3 amplitude was
      associated with less deviant personality scores and better neuropsychological
      performance in healthy subjects. Earlier P3 latency was also associated with
      better neuropsychological performance. The physiological significance of these
      relationships is not yet clear, but these results suggest that neural assemblies
      indexed by P3 may subserve both elemental cognition and healthy personality
      function.

PMID- 15740998
TI  - Personality traits of patients with mood and anxiety disorders.
AB  - Although it is well established that personality traits of patients with mental
      disorder differ significantly from the traits of other persons, differences in
      personality characteristics between different mental disorders have not been
      examined very thoroughly. In this study, we examine personality traits in a large
      sample of outpatients (N=640) with mood and anxiety disorders in differing
      patterns of comorbidity, using the five-factor model of personality. Mood and
      anxiety disorders were assessed using the Composite International Diagnostic
      Inventory, and personality traits were assessed with the NEO Five-Factor
      Inventory (NEO-FFI). Most of the mean scores on the NEO-FFI scales of the study
      population were found to be significantly different from the scale scores of the
      general population. Few differences between NEO-FFI scores for differing patterns
      of mood and anxiety disorders were found. However, clear differences were found
      for subjects with one (mood or anxiety) disorder, subjects with two, and subjects
      with three or more disorders. Neuroticism and agreeableness differed considerably
      in subjects with one disorder compared with subjects with two or more disorders.
      The main conclusion is that personality traits appear to be associated with
      comorbidity and less so with any specific disorder.

PMID- 15741000
TI  - Doxapram-induced panic attacks and cortisol elevation.
AB  - Numerous agents with differing biological properties and central nervous system
      (CNS) effects can induce panic attacks in predisposed individuals. A potential
      explanation of this finding is that panic disorder patients are more likely to
      panic than normal control subjects when given a panicogen due to an excessive
      fear response to somatic arousal. We test this hypothesis by using doxapram, a
      panicogen with minimal CNS effects, to induce panic in patients and control
      subjects. Doxapram was given to six subjects with panic disorder with or without
      agoraphobia and four healthy volunteers. Measures comprised the Acute Panic
      Inventory, the Borg Exertion scale, the 10-point Anxiety Scale, the 10-point
      Apprehension Scale, cortisol, prolactin, and MHPG, all obtained at baseline and
      multiple time points after the doxapram infusion. All panic disorder patients
      panicked with doxapram, whereas no control subjects had a panic attack. Panic
      patients had similar levels of breathlessness with doxapram compared with control
      subjects. Although panic patients had higher levels of anxiety and apprehension,
      these did not change significantly with doxapram compared with control levels.
      Doxapram led to similar increases in cortisol and prolactin in both groups, and
      MHPG was consistently elevated in panic patients, but unaffected by doxapram.
      These results show that doxapram is a useful panicogen in the study of panic
      disorder. Since the panic patients and control subjects had similar levels of
      physiological and psychological arousal, but the panic patients were more likely
      to have a panic attack, this lends support to the concept of a sensitized fear
      network in panic disorder patients.

PMID- 15740999
TI  - Anxiety and salivary cortisol in symptomatic and nonsymptomatic panic patients
      and healthy volunteers performing simulated public speaking.
AB  - Anxiety and salivary cortisol were measured in subjects performing simulated
      public speaking (SPS), a procedure that has been neurobiologically related to
      panic disorder. The subjects were divided into three groups: 18 symptomatic panic
      patients, 16 nonsymptomatic, drug-treated panic patients, and 17 healthy
      controls. In the experimental session, subjective anxiety (Visual Analogue Mood
      Scale) and the total score of the Bodily Symptom Scale (BSS) were higher in
      symptomatic patients than in controls, with nonsymptomatic patients in between.
      Measures of cortisol taken at home showed that the level was higher at 9:00 h
      than at 23:00 h in every group, indicating a normal circadian regulation of the
      hypothalamic-pituitary-adrenal (HPA) axis in panic patients. Also in every group,
      the level of cortisol was high at the beginning of the experimental session and
      decreased after 70 min. This fall parallels the decrease in anxiety and BSS
      ratings, and appears to reflect habituation of initial, anticipatory anxiety.
      Preparation and performance of speech raised anxiety and BSS scores to the
      initial levels, but failed to increase cortisol measured over 60 min, starting at
      the end of the speech. Therefore, SPS does not seem to activate the HPA axis, as
      reported in panic attacks.

PMID- 15741001
TI  - Body shape preference and body satisfaction of Taiwanese and Japanese female
      college students.
AB  - The purpose of this study was to compare the body shape preference and body
      satisfaction of Taiwanese and Japanese female college students. Taiwanese female
      students in Taiwan (n=109) and Japanese female students in Japan (n=144)
      voluntarily completed a four-part Body Image Questionnaire concerning (1)
      demographic background, (2) body figure ratings, (3) cognitive attitude toward
      body size, and (4) subject satisfaction with body characteristics. More Japanese
      than Taiwanese women rated significantly larger body figures and dissatisfaction
      with their body shape and body parts.

PMID- 15741002
TI  - Clozapine: weight gain in a pair of monozygotic twins concordant for
      schizophrenia and mild mental retardation.
AB  - Clozapine is an atypical antipsychotic known to cause considerable weight gain.
      The extent to which genetic factors determine weight gain is unknown. Here we
      report on a pair of female monozygotic twins concordant for schizophrenia and
      mild mental retardation who were treated with clozapine over 5.5 years. One twin
      gained a total of 53.1 kg and had a weight of 107.5 kg (BMI=38.1 kg/m2) at the
      end of the observation period. The other twin gained a total of 48.2 kg and
      finally had a weight of 100.4 kg (BMI=33.8 kg/m2). Because both patients
      experienced considerable weight gain during treatment, our observation suggests
      that the antipsychotic-induced weight gain is under strong genetic control.

PMID- 15741003
TI  - Lack of extrapyramidal side effects predicts quality of life in outpatients
      treated with clozapine or with typical antipsychotics.
AB  - We compared symptom severity and quality of life (QOL) in schizophrenic patients
      adequately treated with typical antipsychotics (TAP) or clozapine (CZP). Groups
      did not differ in symptom severity or QOL. Clozapine caused fewer extrapyramidal
      symptoms. Negative and extrapyramidal symptoms predicted QOL. Similar outcome in
      both groups suggests a common ceiling to antipsychotic efficacy.

PMID- 15741004
TI  - Neuroendocrine (HPA axis) and clinical correlates during fluvoxamine and
      amitriptyline treatment.
AB  - The effect of amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) axis
      activity was compared with that of fluvoxamine in 38 patients suffering from DMS
      IV major depressive disorder. Basal plasma adrenocorticotropic hormone and
      cortisol levels were determined in the so-called "observation window" of an hour
      (08:00-09:00 h), and cortisol levels were determined again at 20:00 h. Clinical
      and biochemical assessments were performed before therapy (T0), at day 14 (T14),
      and at day 42 (T42) of the course of antidepressant treatment. At T0,
      neuroendocrine parameters did not differ in patients from those in controls,
      except for the ratio between cortisol levels at 20:00 h and the mean level of the
      "window" (ratio F20/F8), which was significantly higher, suggesting a
      dysregulation of the circadian pattern of cortisol. Although a decrease in the
      ratio F20/F8 was already apparent at T14 of both treatments, the repeated
      measures analysis of variance failed to demonstrate a significant variation with
      time (T0, T14, and T42) and with treatment (amitriptyline and fluvoxamine) for
      any hormonal measure. At T42, both treated groups showed a similar level of
      clinical improvement. Our results did not demonstrate any effect of
      antidepressant therapy on the cortisol circadian rhythm abnormality.

PMID- 15741005
TI  - Nightmares and terminal insomnia in depressed patients with and without
      melancholic features.
AB  - To investigate the relationship between nightmares and melancholic features (MF)
      in depression, we compared depressed patients with and without MF (n=82 and n=75,
      respectively) regarding the presence of nightmares. Nightmares were significantly
      more frequent in patients with MF. Depressed mood in the morning may be related
      to negative dream content.

PMID- 15741007
TI  - Postoperative radiologic evaluation of the esophagus.
AB  - A wide range of surgical procedures are performed for either benign and malignant
      esophageal lesions, that may be classified as demolitive or conservative
      interventions. The former is characterized by resection and replacement of the
      esophagus with another organ, whereas conservative surgery is obtained preserving
      esophageal function without resection. Knowledge of surgical techniques and major
      complications is extremely important for a correctly performed radiographic study
      and a proper interpretation of the imaging findings. Functional evaluation of the
      operated alimentary tract and early detection of postoperative complications are
      essential for a successful recovery of esophageal surgery patients. We provide a
      brief overview of the main esophageal surgical procedures, reporting our
      experience on postoperative imaging of 104 patients submitted to surgery for
      either benign or malignant esophageal disease during a 6-year period.

PMID- 15741008
TI  - The postoperative stomach.
AB  - Gastric surgery may be performed for the treatment of a variety of benign and
      malignant diseases of the upper gastrointestinal tract, including peptic ulcers
      and gastric carcinoma. Radiographic studies with water-soluble contrast agents
      often are obtained to rule out leaks, obstruction, or other acute complications
      during the early postoperative period. Barium studies may also be obtained to
      evaluate for anastomotic strictures or ulcers, bile reflux gastritis, recurrent
      tumor, or other chronic complications during the late postoperative period. Cross
      sectional imaging studies such as CT are also helpful for detecting abscesses or
      other postoperative collections, recurrent or metastatic tumor, or less common
      complications such as afferent loop syndrome or gastrojejunal intussusception. It
      is important for radiologists to be familiar not only with the radiographic
      findings associated with these various abnormalities but also with the normal
      appearances of the postoperative stomach on radiographic examinations, so that
      such appearances are not mistaken for pseudoleaks or other postoperative
      complications. The purpose of this article is to describe the normal postsurgical
      anatomy after the most commonly performed operations (including partial
      gastrectomy, esophagogastrectomy and gastric pull-through, and total gastrectomy
      and esophagojejunostomy) and to review the acute and chronic complications,
      normal postoperative findings, and major abnormalities detected on radiographic
      examinations in these patients.

PMID- 15741009
TI  - Radiologic evaluation following Roux-en-Y gastric bypass surgery for morbid
      obesity.
AB  - Morbid obesity is an increasing health problem, and bariatric surgery is becoming
      a popular treatment option. Radiologists must be familiar with performing and
      interpreting studies in this patient population. The typical postoperative
      findings of the Roux-en-Y gastric bypass (RYGBP) procedure for morbid obesity on
      upper gastrointestinal (UGI) series are presented. An overview of the potential
      complications that may be diagnosed with contrast studies and computed tomography
      (CT) is provided in addition to a description of potential pitfalls in
      interpreting these studies.

PMID- 15741010
TI  - Atypical complications of gastric bypass surgery.
AB  - Although gastric bypass surgery continues to grow in popularity for weight loss
      and weight maintenance in the morbidly obese, there has been little attention
      given to the imaging of complications associated with these surgeries. The
      purpose of our study is to demonstrate the variety of gastric bypass surgery
      complications that can be identified radiographically, with attention to the more
      unusual complications. This study was performed with institutional Internal
      Review Board approval. We performed a 5-year retrospective review of all patients
      who had undergone gastric bypass surgery, had complications of the surgery, and
      had studies performed in our department to image these complications. These
      studies consisted of contrast fluoroscopy and CT. We identified the more common
      complications of anastomotic stenoses and anastomotic leaks. We also identified
      six unusual complications as follow: (1) internal herniation through the small
      bowel mesentery, (2) internal herniation through the transverse mesocolon, (3)
      external herniation through the abdominal wall incision, (4) enterocutaneous
      fistulas, (5) antiperistaltic construction of the Roux-en-Y, and (6) incorrect
      anstomoses of the Roux limbs resulting in a Roux-en-O configuration. Our findings
      show that a thorough understanding of expected postoperative bowel configuration
      is essential in the evaluation of these patients. In addition, fluoroscopic
      evaluation should assess not only anatomy, but also motility.

PMID- 15741011
TI  - Imaging of small bowel-related complications following major abdominal surgery.
AB  - To recognize and document the small bowel reactions following major abdominal
      surgery is an important key for a correct diagnosis. Usually, plain abdominal
      radiography is the initial imaging examination requested in the immediate
      postoperative period, whereas gastrointestinal contrast studies are used to look
      for specific complications. In some countries, especially in Europe, sonography
      is widely employed to evaluate any acute affection of the abdomen. CT is commonly
      used to assess postoperative abdominal complications; in our institution also CT
      enteroclysis is often performed, to provide additional important informations.
      Radiologist should be able to diagnose less common types of obstruction, such as
      afferent loop, closed loop, strangulating obstruction as well as internal hernia.
      This knowledge may assume a critical importance for surgeons to decide on
      therapy. In this article, we focus our attention on the imaging (particularly CT)
      in small bowel complications following abdominal surgery.

PMID- 15741012
TI  - Systematic approach to the analysis of cross-sectional imaging for surveillance
      of recurrent colorectal cancer.
AB  - Recurrent disease in colorectal cancer occurs in approximately 50% of patients
      who undergo a "curative" operation. Tumor recurrence may occur locally (at the
      anastomotic site), in the mesentery or mesocolon adjacent to the post-operative
      site, in the nodal echelon downstream to the post-operative site, and as distant
      metastases to the peritoneal cavity, liver or lung. Local recurrence at the
      anastomosis is frequently diagnosed at follow-up endoscopic examinations as part
      of screening for metachronous lesions. Other types of recurrences require imaging
      studies, most frequently CT or MR imaging to diagnose. We developed an approach
      to analyze imaging obtained after curative resection of colorectal cancer. Our
      approach is based on the knowledge of patterns of disease spread, of types of
      surgical procedures and of pathologic staging. Using this approach has the
      potential to detect recurrent disease at an early stage because the locoregional
      and nodal spread of this disease is predictable. Early diagnosis of recurrent
      disease, even in asymptomatic cases, allows for more effective treatment that can
      improve the long-term survival of these patients.

PMID- 15741013
TI  - Post colon surgery complications: imaging findings.
AB  - Several standardized types of colonic resections are available in the clinical
      practice. All of them may produce early and late complications. Diagnostic
      imaging plays a pivotal role in the recognition of post-operative colorectal
      complications and provides fundamental information for therapeutic planning. In
      this paper we review the imaging findings of early and late post-operative
      complications of colorectal surgery.

PMID- 15741015
TI  - Imaging evaluation of post pancreatic surgery.
AB  - The role of several imaging techniques in patients submitted to pancreatic
      surgery with special emphasis to single-slice helical computed tomography (CT)
      and multidetector-row CT (MDCT) was reviewed. Several surgical options may be
      performed such as Whipple procedure, distal pancreatectomy, central
      pancreatectomy, and total pancreatectomy. Ultrasound examination may be used to
      detect peritoneal fluid in the early post-operative period as well as lesion
      recurrence in long-term follow-up. Radiological gastrointestinal studies has a
      major role in evaluation of intestinal functionality. In spite of the advent of
      other imaging modalities, CT is the most effective after pancreatic surgery. On
      post-operative CT, the most common findings were small fluid peritoneal or
      pancreatic collections, stranding of the mesenteric fat with perivascular
      cuffing, reactive adenopathy and pneumobilia. In addition, CT may demonstrate
      early (leakage of anastomosis, pancreatico-jejunal fistula, haemorrage, acute
      pancreatitis of the remnant pancreas, peritonitis), and late (chronic fistula,
      abscess, aneurysms, anastomotic bilio-digestive stenosis, perianastomotic ulcers,
      biloma, and intra-abdominal bleeding) surgical complications. In the follow-up
      evaluation, CT may show tumor recurrence, liver and lymph nodes metastasis.
      Magnetic resonance may be used as alternative imaging modality to CT, when renal
      insufficiency or contrast sensitivity prevents the use of iodinated i.v. contrast
      material or when the biliary tree study is primarily requested. The knowledge of
      the type of surgical procedures, the proper identification of the anastomoses as
      well as the normal post-operative imaging appearances are essential for an
      accurate detection of the complications and recurrent disease.

PMID- 15741014
TI  - Radiographic findings of post-operative double stapled trans anal rectal
      resection (STARR) in patient with obstructed defecation syndrome (ODS).
AB  - Longo's procedure of double stapled trans anal rectal resection (STARR) has been
      evocated as surgical treatment of the obstructed defecation syndrome (ODS) in
      patients with rectal mucosal prolapse. The aim of this study was to investigate
      the post-interventional findings of this technique, to help radiologist in
      knowledge of the changed morphology of the rectal lumen, also in attempt to
      recognize some potential related complications.

PMID- 15741016
TI  - MDCT imaging of post interventional liver: a pictorial essay.
AB  - In this pictorial essay, we consider the post operative MDCT findings after liver
      resection, transplantation, surgical managed major trauma and radiofrequency
      ablation of focal lesions. Common complications such as fluid collections,
      hemorrhage, biloma, vascular disease, hematoma, abscesses will be also
      considered.

PMID- 15741017
TI  - Biliary tree and cholecyst: post surgery imaging.
AB  - Recently, with improvements in surgical techniques there has been a substantial
      reduction in the incidence of biliary complications of hepatobiliary surgery.
      Nevertheless, bile duct injuries and other post-cholecystectomy complications are
      a serious problem and a major cause of morbidity and mortality. Early
      complications may include bile duct injury caused by mistakenly placed clips,
      erroneous cutting of bile ducts based on misinterpretation of biliary anatomy,
      periductal bile leakage that causes edema, fibrosis and secondary stricturing,
      and ischemia due to injury to the right hepatic artery. Bile duct strictures are
      the most common of the late complications and can develop a few months or many
      years after surgery. Early detection and accurate diagnosis have a fundamental
      importance for the successful treatment of these complications. Therefore, early
      and meaningful application of the imaging methods immediately after detection of
      the first symptoms is essential. Peroperative ultrasound and direct iodine
      contrast application into the biliary tree (operative cholangiography) are highly
      important for immediate visualization of the complications during surgery.
      Ultrasound can be used to aid in identification of ductal structures and the
      cholangiogram should be obtained to document the anatomy. Plain abdominal film
      could be made in the patients in poor clinical conditions after biliary surgery.
      Oral cholecystography has largely been replaced by ultrasonography (US) for
      evaluation of cholelithiasis and complications like post-cholecystectomy fluid
      collections. The same methodology replaced the conventional intravenous
      cholangiography. Nowadays computed tomography (CT), endoscopic retrograde
      cholangiopancreatography (ERCP), magnetic resonance cholangiography (MRCP) and
      ultrasound (US) have essential roles as primary imaging modalities after biliary
      tree and gallbladder surgery in the evaluation of associated complications and
      residual biliary stones. We review the role of the imaging in complications after
      biliary tree and gallbladder surgery.

PMID- 15741018
TI  - Implications of post-gadolinium MRI results in 13 cases with posterior reversible
      encephalopathy syndrome.
AB  - BACKGROUND: There is a relative lack of definitive information about the contrast
      enhancement characteristics of lesions in posterior reversible encephalopathy
      syndrome (PRES). OBJECTIVE: Evaluation of contrast-enhanced MRI findings in PRES
      with a special emphasis on pathophysiology of post-gadolinium behavior of these
      lesions. MATERIALS AND METHODS: Contrast-enhanced 1.5 T MRI findings and relevant
      clinical data of the patients were retrospectively reviewed on 13 cases (six
      males, seven females; age range: 22-78; mean age 47). Although fluid attenuated
      inversion recovery (FLAIR) and diffusion-weighted MR images were considered for
      identification of the entity, primarily post-contrast T1-weighted MR images were
      searched for traces of enhancement in the lesions. RESULTS: No definitely
      enhancing lesion was identified in the MR images obtained in 6-48 h after onset
      of symptoms (mostly headaches, seizures and cortical visual field deficits) in
      this series. Severity of disease indicated by small hemorrhages, confluence of
      lesions or progression to cytotoxic edema did not seem to alter this result.
      Typical lesion characteristics were consistent with vasogenic edema on FLAIR and
      diffusion MR images. Acute elevation of blood pressure on chronic hypertensive
      background was responsible in four, eclampsia in three, uremia with blood
      pressure fluctuations in three, and cyclosporine-toxicity in three cases.
      CONCLUSION: Although occasional enhancing brain lesions have been reported in the
      literature on PRES, contrast-enhancement of lesions may be a factor of scan
      timing and underlying etiology. Prospective studies with larger series on PRES
      are required for better evaluation of contrast-enhancement in MRI with respect to
      scan timing, which in turn may help understand its pathophysiology better.

PMID- 15741019
TI  - An evaluation of internal carotid artery and cerebral blood flow volume using
      color duplex sonography in patients with vertebral artery hypoplasia.
AB  - INTRODUCTION: Vertebral artery hypoplasia (VAH) may be defined as VA flow volume
      below approximately 30-40 mL/min using color duplex sonography. The aim of this
      study was to evaluate the effect of VAH on internal carotid artery (ICA) flow
      volume and cerebral blood flow (CBF) volume. MATERIAL AND METHODS: In this study,
      17 patients with VAH and 20 control subjects with normal VA flow volume were
      enrolled. The patients and control subjects were 50-75 years aged. The ICA and VA
      flow volumes were determined by using color duplex sonography. The ICA and CBF
      volumes of patients with VAH were compared with control group flow volumes.
      RESULTS: There was no statistically significant difference in flow volumes of
      right, left and sum of both ICA between VAH and control group. However, CBF
      volume was lower in patient with VAH than control group. CONCLUSIONS: Evaluation
      of CBF using color duplex sonography is noninvasive and easily applicable to all
      patients and provides valuable diagnostic data. To the best of our knowledge,
      this is the first study demonstrating lower CBFV and normal ICA flow volume in
      patients with VAH.

PMID- 15741020
TI  - Multi-slice CT angiography of small cerebral aneurysms: is the direction of
      aneurysm important in diagnosis?
AB  - PURPOSE: Multi-slice CT (MSCT) has great potential in evaluation of vascular
      structures. Our purpose was to investigate if there is any difference in
      detection of superiorly, inferiorly and horizontally directed small cerebral
      aneurysms (<5 mm) on MSCTA compared to digital subtraction angiography (DSA) or
      surgery. MATERIALS AND METHODS: One hundred and three consecutive patients who
      underwent MSCTA and DSA or surgery were included in the study. MSCTA and DSA
      results were evaluated independently by two different neuroradiologists who
      performed aneurysm detection, quantitation, and characterization using 2D
      multiplanar reconstructions, 3D maximum intensity projection and volume-rendered
      techniques. FINDINGS: MSCTA detected 49 small cerebral aneurysms (<5 mm) in 37
      (36%) of 103 patients. The overall sensitivity, specificity, and accuracy of
      MSCTA for detecting small aneurysms were 0.85, 0.65, and 0.79, respectively.
      There was moderate agreement between MSCTA and DSA/surgery for detecting small
      aneurysms (kappa: 0.51). The sensitivity of detecting small aneurysms directed
      superiorly, inferiorly and horizontally was 0.94, 0.84, and 0.75, respectively.
      There was no statistically significant difference in detection between small
      aneurysms directed superiorly, inferiorly and horizontally on MSCTA (P > 0.05).
      CONCLUSION: The direction of small cerebral aneurysms is not important in
      diagnosis on multi-slice CT scanners, although the detection of small cerebral
      aneurysms with superior or inferior direction is slightly easier than the
      detection of horizontally directed aneurysms.

PMID- 15741021
TI  - Accuracy of transthoracic sonography in excluding post-interventional
      pneumothorax and hydropneumothorax. Comparison to chest radiography.
AB  - OBJECTIVE: Transthoracic sonography (TS) has evolved as an important imaging
      technique for diagnosing pleural and pulmonary conditions. However, the value of
      TS in either excluding or diagnosing pneumothorax is still under debate. This
      study was conducted to examine whether TS could replace chest radiography for the
      diagnosis of post-interventional pneumothorax and hydropneumothorax. METHODS: 53
      patients (21 females, 32 males; median age 64 years, range 37-94 years), 35 of
      whom underwent transbronchial biopsy (TBB) and 18 patients who had an ultrasound
      guided chest tube placement (U-GCTP) were enrolled in the study. TS was performed
      three hours after either TBB or removal of a chest tube, followed by postero
      anterior chest radiograph (CRX). If any discrepancy between TS, the clinical
      presentation and the CRX became apparent, either a lateral CRX or a computed
      tomography (CT) of the thorax was performed. TS was assessed according to the
      presence of the following criteria: (1) "gliding sign" of the pleural line, (2)
      comet tail artifacts, (3) reverberation artifacts, (4) air/fluid mirror, (5)
      hyperechoic reflectors within the pleural effusion and (6) "lung point". RESULTS:
      In four out of the 53 patients (7.5%) a post-interventional pneumothorax or
      hydropneumothorax occurred. One out of the 35 patients (2.9%) developed a
      pneumothorax after TBB, requiring chest tube placement. Three patients (16.7%)
      developed a hydropneumothorax due to U-GCTP which was detected by sonography but
      was missed by postero-anterior CRX in one patient. The sensitivity, specificity
      and accuracy of TS were 100% in excluding post-interventional
      pneumothorax/hydropneumothorax. CONCLUSION: TS is a cost-effective and safe bed
      side-method, allowing for an immediate exclusion or diagnosis of post
      interventional pneumothorax/hydropneumothorax in patients who have undergone TBB
      or U-GCTP. Thus, these preliminary results suggest that CXR may only be required
      in patients with pneumothorax diagnosed by TS in order to assess its extension or
      to exclude any discrepancy between the TS-result and the clinical presentation.

PMID- 15741022
TI  - Pulmonary manifestations of wegener granulomatosis: CT findings in 57 patients
      and a review of the literature.
AB  - Wegener granulomatosis is a multisystem disease of unknown cause characterized by
      a necrotizing granulomatous vasculitis. In comparison to other vasculitides, the
      lung is the most common organ involved in wegener granulomatosis presenting with
      a very aggressive airways pathology and chronic relapsing course. Chest
      radiographs fail to describe the pattern and distribution of thoracic pathology
      sufficiently, and CT has shown to be more sensitive for detecting lung
      involvement. We present the CT findings of 57 patients with wegener
      granulomatosis and a review of the literature.

PMID- 15741023
TI  - Fast T1- and T2-weighted pulmonary MR-imaging in patients with bronchial
      carcinoma.
AB  - PURPOSE: A prospective study to evaluate the diagnostic potential and limitations
      of three fast MRI sequences in patients with bronchial carcinoma based on the
      comparison with spiral CT. MATERIAL AND METHODS: Three fast chest MRI sequences
      from 20 patients with central or peripheral bronchial carcinoma were evaluated by
      two observers for relation of tumour to adjacent structures, lymph node
      enlargement, additional pulmonary lesions and artefacts. The information from MR
      imaging was compared with the results from spiral CT. MRI comprised a T1-3D-GRE
      breath-hold examination ("VIBE", TR/TE 4.5/1.9 ms, flip-angle 12 degrees , matrix
      502 x 512, 2.5 mm coronal slices), a breath-hold, T2-HASTE sequence (TR/TE
      2000/43 ms, matrix 192 x 256, 10 mm coronal slices) and a respiration-triggered
      T2-TSE sequence (TR/TE 3000-6000/120 ms, matrix 270 x 512, 6 mm transverse
      slices). The FOV was adapted individually (380-480 mm). RESULTS: The presence of
      the primary bronchial carcinoma and infiltration of thoracic structures by tumour
      tissue could be demonstrated by all sequences. VIBE sequence was more suitable
      for detecting small pulmonary nodules than the other MRI examinations, but
      compared to CT still 20% of these lesions were missed. Contrary to VIBE and T2
      weighted TSE scans, HASTE sequence was limited in imaging mediastinal lymph nodes
      due to missing relevant findings in 2/20 patients. HASTE images significantly
      provided the lowest rate of artefacts in imaging lung parenchyma (P < 0.001 in
      peripheral parenchyma), but spatial resolution was limited in this sequence.
      Concerning the differentiation between tumour and adjacent atelectasis (n = 8),
      T2-weighted TSE imaging was superior to CT and VIBE in all cases and to HASTE
      sequence in 4/8 patients. CONCLUSION: The combination of VIBE and HASTE sequence
      allows for an adaequate imaging of thoracic processes in patients with bronchial
      carcinoma, limited only in visualizing small pulmonary nodules. To obtain more
      detail resolution and to differentiate tumour tissue from adjacent atelectasis,
      T2-TSE examination may be added in selected cases.

PMID- 15741024
TI  - Pulmonary infections in the late period after allogeneic bone marrow
      transplantation: chest radiography versus computed tomography.
AB  - PURPOSE: To analyze the capabilities of chest roentgenogram (CXR) and computed
      tomography (CT) in the evaluation of pulmonary infectious disease in the late
      period (>100 days) after allogeneic bone marrow transplantation (BMT). METHODS:
      Ninety-four matched CXR and CT examinations were performed for clinical suspicion
      of infectious lung disease. The time gap between CXR and CT was 48 h at maximum.
      The image pairs were correlated with the patients' clinical course and with the
      results of diagnostic bronchoalveolar lavage (BAL). An unremarkable clinical
      course over the subsequent seven days after imaging and/or negative
      microbiological culture served as the basis for excluding infectious lung
      disease. Positive microbiological culture and/or improvement of symptoms after
      antibiotic therapy were considered as evidence of infectious disease. RESULTS:
      The correlation with the clinical course and/or BAL revealed a significantly
      higher sensitivity, negative predictive value, and accuracy for CT than for CXR
      (89% versus 58%, P < 0.0001; 78% versus 47%, P < 0.0001; 90% versus 68%, P <
      0.0001, respectively). CT was significantly more diagnostic in BAL verified
      fungal and bacterial infections (P < 0.05). CONCLUSION: CT is significantly
      superior to CXR in the evaluation of infectious pulmonary disease in the late
      phase after BMT. Therefore, an unremarkable CXR should be followed by a CT scan
      to reliably detect or to accurately exclude early pulmonary infection in these
      patients.

PMID- 15741025
TI  - Dynamic contrast enhanced MRI in the differential diagnosis of soft tissue
      tumors.
AB  - PURPOSE: The value of the dynamic contrast enhanced-magnetic resonance imaging
      (DCE-MRI) in differentiating benign and malignant soft tissue tumors was
      investigated. MATERIALS AND METHODS: Turbo FLASH DCE-MRI was performed on 22
      subjects (2-74 years) with soft tissue tumors. Enhancement in the first min
      (E(max/1)), second min (E(max/2)) and maximum peak enhancement (E(max)), and
      steepest slope were calculated. Discriminant analyses were performed to reveal
      parametric differences of benign and malignant lesions. RESULTS: Diagnosis of
      benign (N = 10) tumors were hemangioma (n = 3), neurogenic tumor (n = 3) lipoma
      (n = 2), giant cell tumor (n = 1) and desmoid (n = 1), whereas malignant lesions
      (N = 12) were classified as liposarcoma (n = 5), malignant fibrous histiocytoma
      (n = 5) and synovial sarcoma (n = 2). For malignant lesions E(max/1) was 65-198%,
      E(max/2) was 65-145%, E(max) was 78-198%, and steepest slope was 1.45-4.06. For
      benign lesions these values were 4-98%, 5-105%, 7-125% and 0.67-2.57,
      respectively. To determine the relation between the variables analysed, Pearson
      correlation coefficients were calculated. E(max) was found to be highly
      correlated with other variables (rxy > 0.86, P < 0.0001). Consequently, this
      variable was excluded from the discriminant analysis. In order to determine
      discrimination of malignant and benign tumors using E(max/1), E(max/2,) and
      steepest slope of the enhancement curve logistic regression was applied to the
      above mentioned data. When combined these parameters had a 95.5% of overall
      accuracy in classifying benign and malignant lesions (P = 0.004). CONCLUSION: DCE
      MRI parameters that thought to be the surrogate markers of tumoral
      microcirculation and tissue perfusion provides a specific preoperative diagnosis.
      Dynamic imaging parameters are therefore advocated for monitoring the effect of
      chemotherapy in soft tissue tumors.

PMID- 15741026
TI  - In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma.
AB  - In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large
      polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic
      melanoma, from three patients. Spectra were acquired in vivo from voxels wholly
      within the primary tumour or secondary lymph node and were thus uncontaminated by
      signals from adjacent tissue. Tissue biopsies taken after resection of primary
      tumours and secondary lymph nodes were examined by 8.5T magnetic resonance
      spectroscopy (MRS) and the results compared with the in vivo spectra, and with
      spectra from normal skin and a benign skin lesion. There was good agreement
      between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra
      acquired from resected tissue. However, less intense resonances observed at 8.5T
      in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In
      vivo spectra from primary and metastatic melanoma showed high levels of choline
      metabolites. An intense lactate resonance was also present in the in vivo
      spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and
      secondary melanoma showed high levels of choline metabolites and lactate, and
      additional resonances consistent with elevated levels of taurine, alanine,
      lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated
      levels of choline, lactate, taurine, and amino acids appear to be clinically
      useful markers for identifying the pathology of primary and metastatic melanoma.

PMID- 15741028
TI  - The role of surgery in the management of disorders of the temporomandibular
      joint: a critical review of the literature. Part 2.
AB  - The literature is unequivocal in its support for surgery in the management of
      certain disorders of the Temporomandibular joint (TMJ). Unfortunately, the
      literature on TMJ surgery is based more on observation than science since
      randomised clinical trials comparing surgical treatment of the TMJ with medical
      treatment and no treatment (i.e., placebo) do not exist. Because the application
      of scientific principles in clinical studies which involve surgical intervention
      are ethically unfeasible, the true benefit of surgical intervention for
      Temporomandibular Disorders (TMD) may never be conclusively established. Waiting
      for properly designed, placebo controlled, random clinical trials will only
      impede the progress of surgical experience and frustrate the decision making for
      both clinicians and patients. Therefore, the current recommendations for surgery
      must rely on the best available evidence. The aim of this, the second of two
      papers, is to scrutinize the role of TMJ surgery in light of the controversies
      that have appeared in the literature in recent years.

PMID- 15741027
TI  - Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to
      evaluate significant differences between malignant and normal tissue.
AB  - PURPOSE: An ever recurring challenge in diagnostic radiology is the
      differentiation between non-malignant and malignant tissue. Based on evidence
      that microcirculation of normal, non-malignant tissue differs from that of
      malignant tissue, the goal of this study was to assess the reliability of dynamic
      contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these
      two entities. MATERIALS AND METHODS: DcMRI data of rectum carcinoma and gluteus
      maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence
      on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during
      and after constant rate i.v. infusion of a contrast medium (CM). On the basis of
      the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The
      relevance of spatial heterogeneities of microcirculation was investigated by
      relative frequency histograms of the PI-values. RESULTS: A statistically
      significant difference between malignant and normal tissue was found for the mean
      PI-value (P < 0.001; 8.95 ml/min/100 g +/- 2.45 versus 3.56 ml/min/100 g +/-
      1.20). Additionally relative frequency distributions of PI-values with equal
      class intervals of 2.5 ml/min/100 g revealed significant differences between the
      histograms of muscles and rectum carcinoma. CONCLUSION: We could show that
      microcirculation differences between malignant and normal, non-malignant tissue
      can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great
      promise in the aid of cancer assessment, especially in patients where biopsy is
      contraindicated.

PMID- 15741029
TI  - Patients' responses to distraction osteogenesis: a multi-centre study.
AB  - This investigation aimed to compare and contrast practical difficulties
      experienced by 54 children from three different centres (Mexico City, New York,
      Paris) treated with either extra-oral or intra-oral distraction devices. The
      possible effect of distraction osteogenesis on pain/sleeping difficulty, speech
      and eating problems and disturbance of recreational activities and alteration in
      sensation were investigated. It was expected that intra-oral devices would reduce
      the difficulties associated with the distraction process and their psychological
      effect on the child. Some benefits resulting from the use of intra-oral devices
      were identified, these included fewer sleeping problems (P = 0.006) and less
      disturbance of recreational activities (P = 0.002). However, eating and
      maintaining oral hygiene were more problematic with intra-oral devices the
      differences between the intra-oral and extra-oral groups was approaching
      significance at P = 0.07. A major disadvantage of the extra oral device was
      scarring. In both groups the alteration of lip sensation was temporary, pain was
      limited to the time of activation of the distraction device. A high level of
      patients' cooperation was mandatory for successful completion of the treatment.

PMID- 15741030
TI  - Computed tomographic analysis of the position and course of the mandibular canal:
      relevance to the sagittal split ramus osteotomy.
AB  - The aim of this study was to investigate the position and course of the
      mandibular canal through the mandibular ramus using computed tomographic (CT)
      imaging and to relate the findings to performing sagittal split ramus
      osteotomies. The mandibles of 35 patients with skeletal Class III prognathism
      with symmetry (12 males and 23 females) were observed on transaxial computed
      tomograms acquired with a slice thickness of 2 mm. The position and course of the
      mandibular canal from the mandibular foramen to the mandibular body at the level
      of the second molar were measured at four specific locations in the same plane.
      Among the 70 rami examined, lack of a bone marrow space on the buccal side,
      including a fusion type anatomy with no buccal side cortical bone of the
      mandibular canal, were observed at the CT location between the mandibular foramen
      and mandibular angle. Our results suggest that special care must be taken when
      sagittal splitting is performed, and the safest location for the buccal
      corticotomy is anterior to the mandibular angle.

PMID- 15741031
TI  - Neurosensory disturbance after sagittal split and intraoral vertical ramus
      osteotomy: as reported in questionnaires and patients' records.
AB  - This retrospective study aimed at evaluating the long-term incidence of
      neurosensory disturbance (NSD) after sagittal split osteotomy (SSO) and intraoral
      vertical ramus osteotomy (IVRO). Furthermore, a comparison was made between the
      results obtained by questionnaires and information in the patient records in the
      evaluation of nerve function. Finally, the degree of discomfort caused by the NSD
      was evaluated. One hundred and twenty-nine patients, who underwent IVRO (79
      patients) and SSO (50 patients), were included. Questionnaires were mailed to the
      patients at least one year after the operation. The records of all patients, who
      returned the questionnaires, were reviewed. The results of NSD obtained by
      questionnaires and records differed indicating a disagreement between the
      judgement of the surgeon and the patient's opinion. Long lasting NSD was
      underestimated by the surgeon as compared to the patient's subjective symptom.
      Long lasting NSD was reported in 7.5% (questionnaire), 3.8% (record) after IVRO
      and in 11.6% (questionnaire) and 8.1% (record) after SSO.

PMID- 15741032
TI  - Observations on the exploration and external neurolysis of injured inferior
      alveolar nerves.
AB  - The inferior alveolar nerve is sometimes injured during mandibular surgery,
      resulting in altered sensibility. Incomplete recovery may be the result of nerve
      entrapment by scar tissue. Twelve patients underwent external neurolysis of the
      inferior alveolar nerve following prolonged sensory impairment secondary to
      mandibular surgery. The mean time to external neurolysis was 14 months (range 12
      24 months). Five patients demonstrated improvement in sensibility, two patients
      returning to normal sensation. No patient had a worsening of symptoms. The
      results demonstrate that external neurolysis can be a useful step during surgical
      exploration in carefully selected patients.

PMID- 15741033
TI  - Management of mandibular angle fractures using the mandibular angle reduction
      forceps.
AB  - The aim of this study was to determine whether or not the use of the mandibular
      angle reduction forceps decreases the incidence of post-operative complications.
      Forty-six patients, who presented with mandibular angle fractures with a
      displacement or dislocation, were randomly divided into two treatment groups.
      Both groups underwent an open reduction with a single upper border miniplate and
      screw fixation. For 23 patients, the mandibular angle reduction forceps was used
      to aid in fracture reduction, and for 23 patients, the reduction of the fracture
      was achieved using IMF. The post-reduction radiographs showed that the reduction
      forceps group had a higher proportion of precise anatomic alignment of fracture
      than those in the IMF group. In addition, the former group showed a lower rate of
      post-operative complications, as compared to the latter group. This study found
      that the use of the mandibular angle reduction forceps is an important factor for
      decreasing the incidence of post-surgical complication.

PMID- 15741034
TI  - Preoperative radiochemotherapy and radical resection for stages II to IV oral and
      oropharyngeal cancer: grade of regression as crucial prognostic factor.
AB  - The purpose of this study was to assess the prognostic value of histological
      response to preoperative radiochemotherapy in an established multimodal therapy
      concept for advanced oral and oropharyngeal cancer. Two hundred and twenty-two
      patients who underwent preoperative radiochemotherapy (RCT: 50 Gy, mitomycin C
      and fluorouracil) and radical surgery were retrospectively evaluated. Resected
      tumours of all patients were histologically analysed and response to RCT was
      classified in histopathological grades of regression (RG). In a multivariate
      statistical analysis, RG was compared with established factors regarding their
      predictive value for overall and disease-specific survival. The 5-year overall
      survival probability in the different groups of histopathological regression
      grades were: RG1 (no vital tumour): 73.4%, RG2 (minimal tumour remnants
      encompassing less than 5%): 72.1%, RG3 (5-50% vital tumour cells): 41.9%, RG4
      (more than 50% vital tumour): 37.9%. For disease-specific survival probability no
      significant differences were found between both groups of "responders" (RG1 and
      RG2) nor between "non-responders" (RG3 and RG4), whereas responders and non
      responders differed significantly from each other (log-rank test; p < 0.001). T
      classification, N-classification and disease stage, histological grading, tumour
      site, age, and sex had less prognostic value than RG in a Cox regression model.
      In the neoadjuvant multimodal therapy concept, histological response to
      preoperative RCT is a crucial prognostic factor even when surgical R0-resection
      is accomplished. Thus, non-responders have to be regarded as high-risk patients
      for recurrence and may benefit from further therapy.

PMID- 15741035
TI  - Alveolar soft part sarcoma of the head and neck.
AB  - Alveolar soft part sarcoma (ASPS) of the head and neck region has been a rarely
      reported entity. These lesions have a high propensity for distant metastasis. A
      retrospective study of the medical records at our institute, revealed thirty
      eight cases of ASPS. Six of these were of primary head and neck origin. The
      article highlights the aggressive nature of the tumour and the need to arrive at
      a consensus on the treatment protocol.

PMID- 15741036
TI  - A 3-year prospective follow-up study of implant-supported fixed prostheses in
      patients subjected to maxillary sinus floor augmentation with a 80:20 mixture of
      deproteinized bovine bone and autogenous bone Clinical, radiographic and
      resonance frequency analysis.
AB  - The purpose of this prospective clinical study was to evaluate the 3-year outcome
      of 30 maxillary sinus floor augmentations with an autogenous bone-deproteinized
      bovine bone mixture (20:80). A total of 108 dental implants were placed after 6
      months of graft healing. After another 6 months, the occlusion was restored with
      fixed prostheses and followed for 3 years of functional loading. Clinical and
      radiographic examinations of the sinuses and implants, including computerized
      tomography (CT) were performed. The stability of the implants was evaluated by
      means of resonance frequency analyses (RFA). After 3 years of functional loading
      with fixed bridges, 15 of 108 implants were lost giving a cumulative survival
      rate (CSR) of 86%. All followed patients, except one, had fixed bridges in
      function after 3 years of loading. The mean marginal bone loss was 1.3+/-1.1 mm
      after 3 years. RFA showed a mean implant stability quotient (ISQ) value of 66+/
      4.1 after 3 years with no significant difference between implants in grafted and
      residual bone. Examination with CT showed that 67% of the maxillary sinuses were
      healthy prior to treatment and 71% after 3 years of loading. It was concluded
      that grafting of the maxillary sinus with a mixture of autogenous bone and
      deproteinized bovine bone is a reliable procedure.

PMID- 15741037
TI  - A randomized observer blind comparison of bilateral facial ice pack therapy with
      no ice therapy following third molar surgery.
AB  - This study compares the efficacy of Tecnol bilateral facial ice packs with no
      cold therapy in reducing pain, swelling and trismus during the first 24 h
      following third molar surgery. Sixty patients requiring general anaesthesia for
      removal of bilateral, impacted third molar teeth were included and randomly
      assigned to one of two treatment groups. One group received Tecnol bilateral
      facial ice packs following surgery, while a control group received no form of
      cold therapy. Facial ice packs were applied in the recovery room within 15 min of
      the end surgery and patients were asked to use the ice packs continuously for the
      next 24 h. Surgical and anaesthetic techniques as well as pharmacological
      regimens were standardized. Postoperative pain levels were compared hourly, for 4
      h, then on the evening of surgery and the following morning. Facial swelling and
      trismus were compared preoperatively and 24 h postoperatively. No statistically
      significant difference was found between the two treatment groups with respect to
      pain, facial swelling or trismus.

PMID- 15741038
TI  - Mechanical evaluation of mandibular defects reconstructed using osteogenic
      protein-1 (rhOP-1) in a sheep model: a critical analysis.
AB  - Osteoinductive bone morphogenetic proteins (BMPs) have been used extensively in
      experimental and clinical orthopaedic research. It is a natural progression for
      these growth regulators to be tested in the craniofacial region. The aim of this
      investigation was to analyse the mechanical properties of the sheep mandibles
      reconstructed using recombinant human osteogenic protein type 1 (rhOP-1). A
      unilateral 35 mm osteoperiosteal continuity defect was created at the
      parasymphyseal region of the mandible in six adult sheep. The animals were
      sacrificed 3 months after surgery and mechanical properties of the regenerated
      bone at the operated sides (OS) were compared to the corresponding bone at the
      non-operated side (NOS). The regenerated tissue at the OS were then submitted for
      histological and histomorphometric analysis. Although all the animals achieved
      complete bony union, a wide range of mechanical properties was found. The rhOP-1
      induced bone achieved a mean of 36% of the strength of the bone at the NOS (P <
      0.05). The mean value of the stiffness of the OS was 24% of the NOS (P < 0.05).
      While half of the samples of the OS had 'weak' mechanical properties (9-25%
      strength compared to NOS) and a low stiffness (6-18%), the rest showed relatively
      higher strength (47-63%) and were stiffer (35-47%). Unlike the NOS, the operated
      sides failed under tensile stresses and cracks initiated at the superior border
      of the mandible. The wide mechanical variations suggest that further basic bone
      biology research is needed to provide better understanding of the cellular and
      molecular events which take place during the process of osteoinduction.

PMID- 15741039
TI  - Effect of platelet-rich-plasma on cranial distraction osteogenesis in sheep:
      preliminary clinical and radiographic results.
AB  - The purpose of this study was to investigate the effect of platelet-rich-plasma
      (PRP) on cranial distraction osteogenesis. Standardized calvaria critical size
      defects (6 cm x 5 cm) were created in 16 adult female sheep. Bifocal cranial
      transport distraction osteogenesis with autogenous free calvaria bone grafts (2
      cm x 4 cm) was performed at a rate of 1mm once daily to a total of 30 mm. The 16
      sheep involved in the experiment were randomly divided into four groups, four
      animals in each: Group 1 (no PRP, latency 5 days); Group 2 (no PRP, latency 0
      day), Group 3 (PRP, latency 5 days) and Group 4 (PRP, latency 0 day). After a
      consolidation phase of 6 weeks, the animals were sacrificed and specimens
      harvested for conventional radiological and 3D quantitative computer tomographic
      (3D-QCT) assessment. New bone was generated in the distraction zone in all
      groups. There were significantly (P < 0.05) higher densities in the proximal
      region of the distraction regenerate in Group 4 (PRP, latency 0 day) compared to
      Group 2. However, no significant differences in mean density of the total
      distraction regenerate were found, neither in volume of the bony regenerate
      between the experimental groups. This study showed that PRP only had an effect on
      bone regeneration if active distraction was started immediately after application
      of PRP in the distraction gap.

PMID- 15741040
TI  - Tempromandibular joint (TMJ) response to intra-articular dexamethasone injection
      following mechanical arthropathy: a histological study in rats.
AB  - The purpose of this study was to evaluate as well as to compare the effect of
      intra-articular versus intra-peritoneal injection of dexamethasone on synovitis
      induced by trauma to the rat's TMJ. Twenty-seven male Wister rats were included
      in the present study. Induced forced condylar hypermobility achieved through
      opening the rat's mouth manually 10 times for 10 consecutive days. Rats were
      randomized into three groups (3 rats in the control group, and 24 rats in both
      experimental groups). Group I (control group): Rats of this group were left
      without any treatment after induction of synovitis. Group II: Rats were injected
      with a single dose of 1.2 mg/kg dexamethasone intra-articularly (after 10 days).
      Group III: Rats were injected with a single intra-peritoneal injection of 1.2
      mg/kg dexamethasone (after 10 days). Control rats were sacrificed at 6 weeks,
      while rats in Groups II and III were sacrificed at 1 and 6 weeks after drug
      injection, then joints were dissected and processed for histological study. The
      condylar head of the rats injected with intra-articular dexamethasone showed
      resorption with active osteoclastic activity, although the drug was given only
      once. This might be an alarming sign of the severe adverse effect(s) of the local
      injection of dexamethasone.

PMID- 15741041
TI  - Histological analysis of regeneration of temporomandibular joint discs in rabbits
      by using a reconstituted collagen template.
AB  - The aim of this study was to design a biodegradable implant, in the form of a
      reconstituted collagen template in order to promote and support regeneration of
      the temporomandibular joint disc. Bovine collagen (Major Type I) was pepsinized,
      reduced by beta-mercaptoethanol, and reconstituted by glutaraldehyde. The
      reconstitution of the collagen increased the resistance to biological degradation
      by collagenase, optimized the pore size and possessed maximum biological activity
      for tissue regeneration. Forty-four New Zealand rabbits underwent either sham
      surgical procedures or partial temporomandibular joint discectomy. In animals
      that underwent partial discectomy, the discs were replaced by either
      reconstituted collagen templates or subdermal grafts. Some of the surgerized
      animals did not receive any type of implant or disc substitute. Gross and
      histological examination of the surgerized temporomandibular joints was carried
      out at 1-, 2-, and 3-month intervals after surgery on the selected groups of
      animals. Marked arthritic changes were observed after 3 months in the partially
      discectomized joints without implantation. In contrast, the discs, which received
      a reconstituted collagen template or subdermal graft exhibited regeneration and
      nearly normal morpology. No foreign body response was observed in experimental
      groups 3 months after implantation. This study demonstrated that the
      reconstituted collagen did as well as subdermal grafts in supporting and
      facilitating regeneration of the disc and the former was found to have some
      advantages over the latter.

PMID- 15741043
TI  - A patient with untreated tongue carcinoma surviving for 15 years.
AB  - A rare case of untreated tongue carcinoma survived for 15 years is presented. A
      43-year-old Japanese woman was referred to our department with a 1.8 cm x 1.0 cm
      white and red non-indurated lesion of the left border of the tongue. The
      histological examination showed a diagnosis of well-differentiated squamous cell
      carcinoma. We informed the patient and her family that she had a Stage I tongue
      carcinoma and needed to receive treatment immediately. However, they refused
      treatment. Fifteen years later, the patient presented again, complaining of a 55
      mm x 40 mm painful gradual-growth swelling of the same site as before, and the
      clinical stage was T3N2aM0 (Stage IV). The patient agreed to receive radical
      surgery following preoperative chemoradiotherapy this time. Currently the patient
      has been free of recurrence for 4 years. Clinical and immunohistochemical
      features of this rare case are presented and discussed.

PMID- 15741042
TI  - Endovascular treatment of a pseudoaneurysm of the descending palatine artery
      after orthognathic surgery: technical note.
AB  - We report the clinical presentation (relapsing epistaxis after Le Fort I
      osteotomy), craniofacial digital subtraction angiography findings, and
      endovascular embolization through a microcatheter, in a 26-year-old patient with
      a pseudoaneurysm of the descending palatine artery.

PMID- 15741044
TI  - A case of double cancer involving oral malignant melanoma and gastrointestinal
      stromal tumor (GIST).
AB  - We report a very rare case of double cancer involving palatal malignant melanoma
      and gastrointestinal stromal tumor (GIST), a rare tumor of the gastrointestinal
      tract originating from a primitive mesenchymal cell. After chemotherapy,
      radiation therapy, and treatment with interferon and OK-432, the GIST was
      resected and the melanoma disappeared. The patient has had no evidence of
      recurrent tumor, and the patient's clinical course has been uneventful for 1
      year. This is probably the first report of synchronous double cancer involving
      oral malignant melanoma and GIST.

PMID- 15741045
TI  - Solitary fibrous tumor of the orbit: a case report.
AB  - Solitary fibrous tumor is a very rare neoplasm affecting the head and neck. We
      present a case located in the orbit in which clinical, pathological and surgical
      features are reviewed.

PMID- 15741046
TI  - Beneficial effects of intermittent fasting and caloric restriction on the
      cardiovascular and cerebrovascular systems.
AB  - Intermittent fasting (IF; reduced meal frequency) and caloric restriction (CR)
      extend lifespan and increase resistance to age-related diseases in rodents and
      monkeys and improve the health of overweight humans. Both IF and CR enhance
      cardiovascular and brain functions and improve several risk factors for coronary
      artery disease and stroke including a reduction in blood pressure and increased
      insulin sensitivity. Cardiovascular stress adaptation is improved and heart rate
      variability is increased in rodents maintained on an IF or a CR diet. Moreover,
      rodents maintained on an IF regimen exhibit increased resistance of heart and
      brain cells to ischemic injury in experimental models of myocardial infarction
      and stroke. The beneficial effects of IF and CR result from at least two
      mechanisms--reduced oxidative damage and increased cellular stress resistance.
      Recent findings suggest that some of the beneficial effects of IF on both the
      cardiovascular system and the brain are mediated by brain-derived neurotrophic
      factor signaling in the brain. Interestingly, cellular and molecular effects of
      IF and CR on the cardiovascular system and the brain are similar to those of
      regular physical exercise, suggesting shared mechanisms. A better understanding
      of the cellular and molecular mechanisms by which IF and CR affect the blood
      vessels and heart and brain cells will likely lead to novel preventative and
      therapeutic strategies for extending health span.

PMID- 15741047
TI  - Leptin treatment during lactation increases transfer of iodine through the milk.
AB  - We have previously shown that protein restriction during lactation is associated
      with changes in iodine secretion into the milk and that a pup's serum leptin
      concentration was increased at the end of lactation. So, here we evaluate whether
      leptin treatment during lactation affects iodine transfer through the milk to the
      pups. Lactating rats were divided into two groups: the leptin (Lep) group, single
      injected with recombinant rat leptin (8 microg/100g of body weight, daily for 3
      consecutive days), and the control (C) group that received the same volume of
      saline. We studied iodine transfer to the pups through the milk on Days 4, 12 and
      21 of lactation. In those days, the dams were separated from their pups for 4 h.
      Then, the mothers received an injection of 131I (2.22x10(4) Bq ip) and the pups
      were allowed to nurse for 2 h. The animals were sacrificed 2 h later. Leptin,
      total serum T3 and total serum T4 concentrations were higher (P<.05) in pups of
      Lep mothers only on Day 4, suggesting a higher transfer of leptin through the
      milk at this period, probably with a direct stimulatory effect on thyroid hormone
      secretion. In other periods, however, even without a detectable increase in a
      pup's serum leptin concentration, maternal leptin administration increased the
      pup's thyroid iodine uptake (Day 12, 39%; Day 21, 34%), probably caused by a
      higher transfer of iodine through the milk, since they had a higher gastric
      content of 131I on Days 12 (31%) and 21 (128%).

PMID- 15741048
TI  - Effectiveness of moderate green tea consumption on antioxidative status and
      plasma lipid profile in humans.
AB  - The antioxidant activity of green tea (GT) has been extensively studied; however,
      the results obtained from dietary intervention studies are controversial. In the
      present study we investigated the effect of the addition of two cups of GT
      (containing approximately 250 mg of total catechins) to a controlled diet in a
      group of healthy volunteers with respect to a group following the same controlled
      diet but not consuming GT. Antioxidant status and lipid profile in plasma, the
      resistance from oxidative damage to lipid and DNA, and the activity of
      glutathione peroxidase (GPX) in isolated lymphocytes were measured at the
      beginning and the end of the trial. After 42 days, consumption of GT caused a
      significant increase in plasma total antioxidant activity [from 1.79 to 1.98
      micromol Trolox equivalent (TE)/ml, P<.001], significant decreases in plasma
      peroxides level (from 412 to 288 Carr U, P<.05) and induced DNA oxidative damage
      in lymphocytes (from 14.2% to 10.1% of DNA in tail, P<.05), a moderate although
      significant decrease in LDL cholesterol (from 119.9 to 106.6 mg/dL, P<.05) with
      respect to control. The present study suggests the ability of GT, consumed within
      a balanced controlled diet, to improve overall the antioxidative status and to
      protect against oxidative damage in humans.

PMID- 15741049
TI  - Insulin-dependent glycogen synthesis is delayed in onset in the skeletal muscle
      of food-deprived aged rats.
AB  - Insulin resistance with aging may be responsible for impaired glycogen synthesis
      in the skeletal muscle of aged rats and contribute to the well-known decreased
      ability to respond to stress with aging. For this reason, to assess the ability
      of the skeletal muscle to utilize glucose for glycogen synthesis during aging,
      the time course of glycogen synthesis was continuously monitored by 13C nuclear
      magnetic resonance for 2 h in isolated [13C] glucose-perfused gastrocnemius
      plantaris muscles of 5-day food-deprived adult (6-8 months; n=10) or 5-day food
      deprived aged (22 months; n=8) rats. [13C] glucose (10 mmol/L) perfusion was
      carried out in the presence or absence of an excess of insulin (1 micromol/L).
      Food deprivation only decreased glycogen level in adult rats (8.9+/-2.4
      micromol/g in adults vs. 35.6+/-2.4 micromol/g in aged rats; P<.05). In the
      presence of an excess of insulin, muscle glycogen synthesis was stimulated in
      both adult and aged muscles, but the onset was delayed with aging (40 min later).
      In conclusion, this study highlights the important role of glycogen depletion in
      stimulating glycogen synthesis in muscles. Consequently, the absence of glycogen
      depletion in response to starvation in aged rats may be the origin of the delay
      in insulin-stimulated glycogen synthesis in the skeletal muscle. Glycogen
      synthesis clearly was not impaired with aging.

PMID- 15741050
TI  - Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human
      colon cancer cells.
AB  - Quercetin has chemoprotective properties in experimental colon cancer models, and
      in vitro studies have demonstrated that quercetin inhibits HT-29 colon cancer
      cell growth. ErbB2 and ErbB3 receptor tyrosine kinases have been associated with
      the development of human colon cancer, and the expressions of both receptors are
      high in HT-29 cells. In this study, we assessed quercetin regulation of HT-29 and
      SW480 cell apoptosis and the influence of quercetin on the protein expression of
      ErbB2, ErbB3, Akt, Bax and Bcl-2. We cultured HT-29 cells in the presence of
      various concentrations (0, 25, 50, or 100 micromol/L) of quercetin or rutin.
      Quercetin inhibited HT-29 cell growth in a dose-dependent manner, whereas rutin
      had no effect on the cell growth. DNA that was isolated from cells treated with
      50 micromol/L of quercetin exhibited an oliogonucleosomal laddering pattern
      characteristic of apoptotic cell death. Western blot analysis of cell lysates
      revealed that Bcl-2 levels decreased dose-dependently in cells treated with
      quercetin, but Bax remained unchanged. Quercetin increased levels of cleaved
      caspase-3 and the 89-kDa fragment of poly (ADP-ribose) polymerase. In addition,
      phosphorylated Akt levels were markedly lower in cells treated with 25 micromol/L
      quercetin, but total Akt levels decreased only at 100 micromol/L quercetin.
      Furthermore, a dose-dependent decrease in ErbB2 and ErbB3 levels was detected in
      quercetin-treated cells. The results obtained using SW480 cells were similar to
      those obtained with HT-29 cells. In conclusion, we have shown that quercetin
      inhibits cell growth and induces apoptosis in colon cancer cells, and that this
      may be mediated by its ability to down-regulate ErbB2/ErbB3 signaling and the Akt
      pathway.

PMID- 15741052
TI  - Modulation effect of tea polyphenol toward N-methyl-N'-nitro-N-nitrosoguanidine
      induced precancerous gastric lesion in rats.
AB  - The chemopreventive effect of tea polyphenol (TP) on precancerous gastric lesion
      was examined. A rat model was established by gavage of N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), and different concentrations of TP were given to Wistar
      rats in drinking water during the 16 weeks of the experiment. The
      histopathological data showed an effect of TP to lighten the lesions induced by
      MNNG. By flow cytometry, we demonstrated that TP treatment decreased the
      proliferation and apoptosis index (AI) induced by MNNG. The arrest in the G0-G1
      phase of the cell cycle was also obtained. The results suggested that TP had
      preventive effect against gastric carcinogenesis at the preinitiation stage and
      such prevention may be related to the modulation of the balance of cell death and
      cell proliferation.

PMID- 15741051
TI  - The effect of fish oil on physical aggression in schoolchildren--a randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVES: The aim of the study was to investigate whether fish oil
      supplementation affected Japanese schoolchildren's behavior, with changes in
      aggression over time as the primary endpoint. DESIGN AND SUBJECTS: A placebo
      controlled double-blind study with 166 schoolchildren 9-12 years of age was
      performed. The subjects of the fish oil group (n=83) took fish oil-fortified
      foods (bread, sausage and spaghetti). These foods were provided in amounts such
      that each subject in the fish oil group had an intake of 3600 mg of
      docosahexaenoic acid+840 mg of eicosapentaenoic acid (EPA)/week for 3 months. The
      rest (the controls, n=83) took control supplements. At the start and end of the
      study, psychological tests were performed to assess their aggression. RESULTS:
      Physical aggression assessed by Hostility-Aggression Questionnaire for Children
      in girls increased significantly (median: 13 to 15, n=42) in the control group
      and did not change (13 to 13, n=43) in the fish oil group with a significant
      intergroup difference (P=.008) with baseline as covariate. The changes in
      physical aggression scores over time and those of the ratio of EPA/arachidonic
      acid in RBC (DeltaEPA/AA) were significantly correlated in girls who agreed to
      blood collection (r=-.53, P=.01, n=23). On the contrary, there were no
      significant changes in physical aggression in boys. Aggression against others
      (extraggression) assessed by Picture Frustration Study did not change in the
      control group (median: 5 to 5) but increased significantly in the fish oil group
      (4 to 5) with a significant intergroup difference (P=.02) with baseline as
      covariate. These changes in extraggression might be explained partly by
      significantly lower baseline values of extraggression in the fish oil group
      (P=.02) than in the control group. There were no significant correlations between
      Deltaextraggression and DeltaEPA/AA in blood-sampled children (n=49). Impulsivity
      of girls assessed by parents/guardians using the diagnostic criteria for
      attention deficit/hyperactivity disorder of DSM-IV was reduced in the fish oil
      group (1 to 0) with a significant (P=.008) intergroup difference from the control
      group (1 to 1). There were no significant correlations between Deltaimpulsivity
      and DeltaEPA/AA in blood-sampled girls. In males, impulsivity reduced in both
      groups without any intergroup differences. CONCLUSION: There is a possibility
      that changes in fatty acid nutrition might affect physical aggression especially
      in girls.

PMID- 15741053
TI  - Trans fatty acids alter the lipid composition and size of apoB-100-containing
      lipoproteins secreted by HepG2 cells.
AB  - This study was conducted to determine the secretion rate and composition of
      lipoproteins secreted by HepG2 cells as influenced by the type of fatty acid
      present in the incubation medium. Cells were preincubated for 24 h with palmitic,
      oleic, elaidic, linoleic or conjugated linoleic acid (CLA), and the lipoproteins
      secreted during a subsequent incubation period of 24 h were collected for
      analysis. The secretion rate of apolipoprotein B-100 (apoB) was significantly
      greater in HepG2 cells preincubated with elaidic acid compared with those
      preincubated with palmitic or oleic acid; apoB secretion was greater in cells
      preincubated with CLA compared with those preincubated with linoleic acid. The
      lipid composition of secreted lipoproteins was also influenced by fatty acid
      treatment, resulting in significantly smaller lipoprotein particles secreted by
      cells preincubated with elaidic acid and CLA compared with those secreted by
      cells treated with oleic acid and linoleic acid, respectively. Our results are
      relevant to human metabolism for the following reasons: (1) the size of plasma
      low-density lipoproteins (LDLs) is determined, at least in part, by the
      composition of apoB-containing lipoproteins secreted by the liver; (2) small
      plasma LDL particles are associated with an increased risk of coronary heart
      disease; and (3) specific dietary fatty acids can affect the composition and size
      of plasma LDLs, thereby imparting a relative atherogenicity to plasma LDLs
      independent of LDL cholesterol concentration. The present study therefore
      suggests that elaidic acid and CLA promote the hepatic secretion of small apoB
      containing lipoproteins, which could lead to an increased production of small
      plasma LDL particles.

PMID- 15741054
TI  - Comparison of stearidonic acid and alpha-linolenic acid on PGE2 production and
      COX-2 protein levels in MDA-MB-231 breast cancer cell cultures.
AB  - The bioactivity of stearidonic acid (SDA, 18:4n-3) and alpha-linolenic acid (LNA,
      18:3n-3) on cyclooxygenase-2 (COX-2) enzyme expression and prostaglandin E2
      (PGE2) production has not been evaluated. This investigation examined the effects
      of SDA and LNA on PGE2 biosynthesis and COX-2 protein and mRNA levels in MDA-MB
      231 human breast cancer cells. Cells were supplemented with SDA, LNA, linoleic
      acid and arachidonic acid (AA) at concentrations ranging from 10 to 200 microM.
      At 50 and 200 microM, both SDA and LNA treatments and their combinations reduced
      PGE2 production as compared with AA. At 50 microM, SDA treatment also lowered the
      COX-2 protein level as compared with the vehicle, but this reduction was not
      observed with the LNA treatment. Gas chromatographic analysis of fatty acids in
      cellular lipids of breast cancer cells revealed that SDA led to significantly
      greater concentrations of 20:5n-3 and other long-chain (LC) n-3 polyunsaturated
      fatty acids (PUFAs) (20:4n-3, 22:4n-3 and 22:5n-3) as compared with the LNA
      treatment. Both SDA and LNA reduced the level of 20:4n-6; however, SDA was more
      effective than LNA in decreasing the ratio of n-6/n-3 PUFAs in cells. In
      addition, SDA was more potent than LNA in suppressing the expression of the COX-2
      gene, which was associated with the reduction in the levels of nuclear factor
      kappa B and peroxisome proliferator-activated receptor gamma mRNA. This study
      showed that although PGE2 production in MDA-MB-231 breast cancer cells was not
      significantly different between the SDA and LNA treatments, SDA was more
      effective than LNA in converting into LC n-3 PUFAs and in reducing COX-2 protein
      and mRNA levels.

PMID- 15741055
TI  - Biosensors 2004. Proceedings of the 8th World Congress on Biosensors, 24-26 May
      2004, Granada, Spain.

PMID- 15741056
TI  - In vivo glucose monitoring: the clinical reality and the promise.
AB  - Glucose monitoring is an essential component of modern diabetes management. Three
      in vivo glucose sensors are now available for clinical use: a subcutaneously
      implanted amperometric enzyme electrode, a reverse iontophoresis system and a
      microdialysis-based device. Improvements in glucose-sensing technology continue
      to be sought, e.g. wired enzyme technology, viscometric affinity sensing and
      totally implanted glucose sensors. Non-invasive glucose sensing is the ultimate
      goal of glucose monitoring, but the most investigated approach, near-infrared
      (NIR) spectroscopy, is presently too imprecise for clinical application.
      Fluorescence-based glucose sensing offers several advantages and we are
      investigating strategies which include NIR-based fluorescence resonance energy
      transfer using concanavalin A/dextran; changes in the intrinsic fluorescence of
      hexokinase encapsulated in sol-gel; and non-invasive glucose monitoring of cells
      by measuring glucose-related changes in NADP(H).

PMID- 15741057
TI  - Biosensors for marine applications. We all need the sea, but does the sea need
      biosensors?
AB  - The aim of the paper is to explain the rationale behind marine biosensor
      applications, give an overview of measurement strategies currently employed,
      summarise some of the relevant available biosensor technology as well as
      instrumentation requirements for marine sensors and attempt a forward look at
      what the future might hold in terms of needs and developments. Application areas
      considered are eutrophication, organism detection, food safety, pollutants, trace
      metals and ecotoxicology. The drivers for many of these studies are discussed and
      the policy environment for current and future measurements is outlined.

PMID- 15741058
TI  - Sonochemically fabricated acetylcholinesterase micro-electrode arrays within a
      flow injection analyser for the determination of organophosphate pesticides.
AB  - This report describes the development of novel sonochemically fabricated,
      bioengineered acetylcholinesterase and polyaniline carbon/cobalt phthalocyanine
      biosensors for the ultra-sensitive determination of a number of different
      pesticides. Arrays of this type typically have population micro-electrode
      densities of up to approximately 2 x 10(5) cm(-2); these represent the highest
      micro-electrode population densities reported to date by any fabrication means.
      The enzymatic response of the sensors is inhibited upon incubation with the
      pesticide, and we have shown that Dichlorvos, Parathion and Azinphos may be
      determined down to concentrations of approximately 1 x 10(-17) M, approximately 1
      x 10(-16) M and approximately 1 x 10(-16) M, respectively. These lower limits of
      detection are lower than otherwise achievable by any other analytical approach.
      Measurements were performed within a custom built flow injection system that
      operates at a constant flow of 1 ml min(-1). Sensor stability studies were also
      performed whereby a stabilizer mixture of sucrose and polygalacturonic acid was
      added to the immobilised enzyme matrix at the working electrode and left to dry.
      Sixty-five percent of the initial enzyme activity was found to remain after a
      period of 92 days to allow storage of these electrodes and facilitating
      transportation if required.

PMID- 15741059
TI  - APDS: the autonomous pathogen detection system.
AB  - We have developed and tested a fully autonomous pathogen detection system (APDS)
      capable of continuously monitoring the environment for airborne biological threat
      agents. The system was developed to provide early warning to civilians in the
      event of a bioterrorism incident and can be used at high profile events for short
      term, intensive monitoring or in major public buildings or transportation nodes
      for long-term monitoring. The APDS is completely automated, offering continuous
      aerosol sampling, in-line sample preparation fluidics, multiplexed detection and
      identification immunoassays, and nucleic acid-based polymerase chain reaction
      (PCR) amplification and detection. Highly multiplexed antibody-based and duplex
      nucleic acid-based assays are combined to reduce false positives to a very low
      level, lower reagent costs, and significantly expand the detection capabilities
      of this biosensor. This article provides an overview of the current design and
      operation of the APDS. Certain sub-components of the ADPS are described in
      detail, including the aerosol collector, the automated sample preparation module
      that performs multiplexed immunoassays with confirmatory PCR, and the data
      monitoring and communications system. Data obtained from an APDS that operated
      continuously for 7 days in a major U.S. transportation hub is reported.

PMID- 15741060
TI  - Novel electrical detection of label-free disease marker proteins using
      piezoresistive self-sensing micro-cantilevers.
AB  - We report an electro-mechanical biosensor for electrical detection of proteins
      with disease markers using self-sensing piezoresistive micro-cantilevers.
      Electrical detection, via surface stress changes, of antigen-antibody (Ag-Ab)
      specific binding was accomplished through a direct nano-mechanical response of
      micro-fabricated self-sensing micro-cantilevers. A piezoresistive sensor measures
      the film resistance variation with respect to surface stress caused by
      biomolecules specific binding. When specific binding occurred on a functionalized
      Au surface, surface stress was induced throughout the cantilever, resulting in
      cantilever bending and resistance change of the piezoresistive layer. The
      cantilever biosensors were used for the detection of prostate specific antigen
      (PSA) and C-reactive proteins (CRP), which are a specific marker of prostate
      cancer and cardiac disease. From the above experiment, it was revealed that the
      sensor output voltage was proportional to the injected antigen concentration
      (without antigen, 10 ng/ml, 100 ng/ml, 1 microg/ml). PSA and CRP antibodies were
      found to be very specific for their antigens, respectively. This indicated that
      the self-sensing micro-cantilever approach is beneficial for detecting disease
      markers, and our piezoresistive micro-cantilever sensor system is applicable to
      miniaturized biosensor systems.

PMID- 15741061
TI  - Detection of TP53 mutation using a portable surface plasmon resonance DNA-based
      biosensor.
AB  - A DNA-based surface plasmon resonance (SPR) biosensor has been developed for the
      detection of TP53 mutation using the inexpensive and commercially available
      instrument, SPREETA SPR-EVM-BT, from Texas Instruments. A direct immobilisation
      procedure, based on the coupling of thiol-derivatised oligonucleotide probes
      (Probe-C6-SH) to bare gold sensor surfaces, was optimized using synthetic
      oligonucleotides. Hybridisation reactions between the immobilised probe and a
      short sequence (26 mer) complementary, non-complementary and one-point mutation
      DNA were then investigated. The main analytical parameters of the sensor system
      were studied in detail including selectivity, sensitivity, reproducibility and
      analysis time. Finally, the sensor system was successfully applied to polymerase
      chain reaction (PCR)-amplified real samples, DNA extracted from both normal, wild
      type, (Jurkat) and mutated (Molt 4), carrying the mutation at codon 248 of the
      TP53 cell lines. The results obtained demonstrate that the DNA-based SPR
      biosensor was able to distinguish sequences present in the various samples that
      differ only by one base; and hence, it appears to be a strong candidate technique
      for the detection of gene mutation.

PMID- 15741062
TI  - Culture of neural cells on polymers coated surfaces for biosensor applications.
AB  - We focused our study on the olfactory cells growth on biocompatible polymer films
      electrodeposited on a silicon microsystem. Several substrates such as
      polyethyleneimine (PEI), polypropyleneimine (PPI), and polypyrrole (PPy), acting
      as potentially good candidates for cell culture, were tested in order to allow
      cells to adhere and proliferate. During their growth, the evolution of their
      morphology was monitored using both confocal microscope and immunohistochemistry,
      leading to the conclusion of a normal development. An estimation of the adhesion
      and proliferation rates of rat neuronal cell cultures indicated that PEI and PPI
      were the best substrates for cultivating olfactory cells.

PMID- 15741063
TI  - Micro-analytical GO/HRP bioreactor for glucose determination and bioprocess
      monitoring.
AB  - A bi-enzymatic micro-analytical bioreactor integrated in a FIA system for glucose
      measurements is described. Its robustness and small dimensions (working volume of
      about 70 microl containing approximately 1.2 mg GO and 0.26 mg HRP) make it easy
      to operate. The column is based on immobilisation of glucose oxidase (GO) and
      horseradish peroxidase (HRP) on alkylamine controlled pore glass (CPG) beads. The
      column has excellent shelf life (no significant loss of activity after 1 year if
      kept at 4 degrees C), and a very high operational stability that was demonstrated
      through extensive usage for glucose determinations over 1 year period during
      which the column retained almost all of its activity. More importantly, this
      operational stability allows glucose monitoring in the culture media without a
      decay of signal over the experiment time and consequently no signal correction or
      re-calibration is needed. This high operational stability was also confirmed by
      continuous glucose conversion with 30% activity loss after converting quantity of
      glucose equivalent to 21600 FIA injections of 20 microl with 1.7 mM glucose. Such
      good performance is a result of an optimised immobilisation method and moreover
      of the implementation of in situ enzyme stabilisation strategy which consisted on
      promoting the instantaneous H2O2 consumption produced by the GO. This strategy
      has the additional advantage of allowing concomitant assay of the H2O2 based on
      the HAP catalysed co-oxidation of phenol-4-sulphonic acid (PSA) in the presence
      of 4-aminoantipyrine (4-AAP). The glucose measurements are reproducible with high
      precision against the standard HPLC method. Linear range and sensitivity depend
      on sample injection volume; the upper limit is about 1.1 g/l. Lower detection
      limit is 10mg/l. The column performance has been validated for E. coli and S.
      cerevisiae fermentation monitoring, and glucose measurements in an animal cell
      culture (rat Langerhans islets).

PMID- 15741065
TI  - Development of a gas chromatography silicon-based microsystem in clinical
      diagnostics.
AB  - The accurate determination of biological parameters by means of rapid, on-line
      measurements at low-concentrations is an important task within the fields of
      pharmaceutical screening and medical diagnostic. Nevertheless, in biological
      samples, the analytes of interest are present as minor components in complex
      mixtures and with interfering species. Biosensors are the best candidates for
      these applications providing a direct solution to this need of accuracy, but
      their intrinsic selectivity often excludes all the other components in the
      sample. A separation step introduced prior to the sensing component could allow
      both the increase of selectivity with respect the interfering species and the
      identification of a large spectrum of molecular components in the sample. This
      work reports the development of a silicon-based integrated separation microsystem
      for gas chromatography aimed to biomedical applications, with particular emphasis
      to monitor the homovanillic acid (HVA) and vanillylmandelic acid (VMA) ratios in
      mass population screening for neuroblastoma diagnosis and prognosis. The
      miniaturised system consists of two main modules: (i) a metal oxide semiconductor
      detector and (ii) a micromachined separation capillary column. As first step, the
      metal oxide semiconductor capability to detect HVA and VMA has been demonstrated.
      Then, a technology for a silicon separation capillary microcolumn including the
      on-chip gas sensor housing has been proposed and a first prototype has been
      developed. The proposed microsystem is an analytical device with biosensing
      capabilities for diagnostic and biomedical applications, which yield an
      electronic signal proportional to the concentration of a specific analyte or
      group of analytes.

PMID- 15741064
TI  - Biofuel cell based on direct bioelectrocatalysis.
AB  - A biofuel cell, consisting of two 3mm diameter carbon rod electrodes and
      operating at ambient temperature in aqueous solution, pH 6, is described. Biofuel
      cell based on enzymes able to exchange directly electrons with carbon electrodes
      was constructed and characterized. Anode of the biofuel cell was based on
      immobilized Quino-hemoprotein alcohol dehydrogenase from Gluconobacter sp. 33 (QH
      ADH), cathode on co-immobilized glucose oxidase from Aspergilus niger (GO(x)) and
      microperoxidase 8 from the horse heart (MP-8) acting in the consecutive mode. Two
      enzymes GO(x) and MP-8 applied in the design of biofuel cell cathode were acting
      in consecutive mode and by hydrogen peroxide oxidized MP-8 was directly accepting
      electrons from carbon rod electrode. If ethanol was applied as an energy source
      the maximal open circuit potential of the biofuel cell was -125 mV. If glucose
      was applied as energy source the open circuit potential of the cell was +145 mV.
      The maximal open circuit potential (270 mV) was achieved in the presence of
      extent concentration (over 2 mM) of both substrates (ethanol and glucose).
      Operational half-life period (tau(1/2)) of the biofuel cell was found to be 2.5
      days.

PMID- 15741066
TI  - Optical solid-state detection of organophosphates using organophosphorus
      hydrolase.
AB  - We have developed a sensor surface for optical detection of organophosphates
      based on reversible inhibition of organophosphorus hydrolase (OPH) by copper
      complexed meso-tri(4-sulfonato phenyl) mono(4-carboxy phenyl) porphyrin
      (CuC1TPP). OPH immobilized onto glass microscope slides retains catalytic
      activity for more than 232 days. CuC1TPP is a reversible, competitive inhibitor
      of OPH, binding at the active site of the immobilized enzyme. The absorbance
      spectrum of the porphyrin-enzyme complex is measured via planar waveguide
      evanescent wave absorbance spectroscopy using a blue LED as a light source and an
      Ocean Optics USB2000 as the spectrophotometer. The characteristics of the
      absorbance spectrum of CuC1TPP are specific and different when the porphyrin is
      bound to the enzyme or is bound non-specifically to the surface of the slide.
      Addition of a substrate of OPH such as one of the organophosphates paraoxon,
      coumaphos, diazinon, or malathion displaces the porphyrin from the enzyme
      resulting in reduced absorbance intensity at 412 nm. Absorbance changes at 412 nm
      show log-linear dependence on substrate concentration. Paraoxon concentrations
      between 7 parts per trillion (ppt) and 14 parts per million (ppm) were
      investigated and a 3:1 S/N detection limit of 7 ppt was determined.
      Concentrations of 700 ppt to 40 ppm were investigated for diazinon, malathion,
      and coumaphos with detection limits of 800 ppt, 1 part per billion, and 250 ppt,
      respectively. This optical technique does not require the addition of reagents or
      solutions other than the sample and absorbance spectra can be collected in less
      than 6 s.

PMID- 15741067
TI  - A multi-biosensor based on immobilized Photosystem II on screen-printed
      electrodes for the detection of herbicides in river water.
AB  - A multi-biosensor for detection of herbicides and pollutants was constructed
      using various photosynthetic preparations as biosensing elements. The
      photosynthetic thylakoid from Spinacia oleracea L., Senecio vulgaris and its
      mutant resistant to atrazine were immobilized with (BSA-GA) on the surface of
      screen-printed sensors composed of a graphite-working electrode and Ag/AgCl
      reference electrode deposited on a polymeric substrate. The biosensor was
      composed of four flow cells with independent illumination of 650 nm to activate
      electron transfer in Photosystem II. The principle of the detection was based on
      the fact that herbicides selectively block electron transport activity in a
      concentration-dependent manner and that the four PSII biomediators show
      differential recognition activity toward herbicides. Changes of the activity were
      registered amperometrically as rate of photoreduction of the artificial electron
      acceptor DQ. The setup resulted in a reusable herbicide multibiosensor with a
      good stability (half-life of 16.7 h for spinach thylakoids) and limit of
      detection of about 10(-8) M for herbicides recovered in spring in river.

PMID- 15741068
TI  - Novel planar glucose biosensors for continuous monitoring use.
AB  - Novel planar glucose biosensors to be used for continuous monitoring have been
      developed. The electrodes are produced with the "screen printing" technique, and
      present a high degree of reproducibility together with a low cost and the
      possibility of mass production. Prior to enzyme immobilisation, electrodes are
      chemically modified with ferric hexacyanoferrate (Prussian Blue). This allows the
      detection of the hydrogen peroxide produced by the enzymatic reaction catalysed
      by GOD, at low applied potential (ca. 0.0 V versus Ag/AgCl), highly limiting any
      electrochemical interferences. The layer of Prussian Blue (PB) showed a high
      stability at the working conditions (pH 7.4) and also after 1 year of storage dry
      at RT, no loss of activity was observed. The assembled glucose biosensors, showed
      high sensitivity towards glucose together with a long-term operational and
      storage stability. In a continuous flow system, with all the analytical
      parameters optimised, the glucose biosensors detected glucose concentration as
      low as 0.025 mM with a linear range up to 1.0mM. These probes were also tested
      over 50-60 h in a continuous flow mode to evaluate their operational stability. A
      0.5 mM concentration of glucose was continuously fluxed into a biosensor wall-jet
      cell and the current due to the hydrogen peroxide reduction was continuously
      monitored. After 50-60 h, the drift of the signal observed was around 30%.
      Because of their high stability, these sensors suggest the possibility of using
      such biosensors, in conjunction with a microdialysis probe, for a continuous
      monitoring of glucose for clinical purposes.

PMID- 15741069
TI  - Enzyme-based impedimetric detection of PCR products using oligonucleotide
      modified screen-printed gold electrodes.
AB  - This paper describes the optimisation and the analytical performances of an
      enzyme-based electrochemical genosensor, developed using disposable
      oligonucleotide-modified screen-printed gold electrodes. The immobilisation of a
      thiol-tethered probe was qualitatively investigated by means of faradic impedance
      spectroscopy. Impedance spectra confirmed that the thiol moiety unambiguously
      drives the immobilisation of the oligonucleotide probe. Furthermore, both probe
      surface densities and hybridisation efficiencies were quantified through
      chronocoulometric measurements. Electrochemical transduction of the hybridisation
      process was also performed by means of faradic impedance spectroscopy, after
      coupling of a streptavidin-alkaline phosphatase conjugate and bio-catalysed
      precipitation of an insoluble and insulating product onto the sensing interface.
      Chronocoulometric results allowed discussion of the magnitude of hybridisation
      signals in terms of probe surface densities and their corresponding hybridisation
      efficiency. The genosensor response varied linearly (r2 = 0.9998) with the
      oligonucleotide target concentration over three orders of magnitude, between 12
      pmol/L and 12 nmol/L. The estimated detection limit was 1.2 pmol/L (i.e., 7.2 x
      10(6) target molecules in 10 microL of sample solution). The analytical
      usefulness of the impedimetric genosensor was finally demonstrated analysing
      amplified samples obtained from the pBI121 plasmid and soy and maize powders
      containing 1 and 5% of genetically modified product. Sensing of such unmodified
      amplicons was achieved via sandwich hybridisation with a biotinylated signaling
      probe. The electrochemical enzyme-amplified assay allowed unambiguous
      identification of all genetically modified samples, while no significant non
      specific signal was detected in the case of all negative controls.

PMID- 15741070
TI  - Electrochemical investigation of cellobiose dehydrogenase from new fungal sources
      on Au electrodes.
AB  - Following previous electrochemical investigations of cellobiose dehydrogenase
      (CDH), the present investigation reports on the initial screening of the
      electrochemistry of three new CDHs, two from the white rot basidiomycetes
      Trametes villosa and Phanerochaete sordida and one from the soft rot ascomycete
      Myriococcum thermophilum, for their ability to directly exchange electrons with
      10 different alkanethiol-modified Au electrodes. Direct electron transfer (DET)
      between the enzymes and some of the modified Au electrodes was shown, both, in
      the presence and in the absence of cellobiose. However, the length and the head
      functionality of the alkanethiols drastically influenced the efficiency of the
      DET reaction and also influenced the effect of pH on the biocatalytic/redox
      currents, suggesting the importance of structural/sequence differences between
      these CDH enzymes. In this respect, the white rot CDHs exhibit excellent
      biocatalytic and redox currents, whereas for the soft rot CDH the DET
      communication is much less efficient. Cyclic voltammograms indicate that the heme
      domain of the CDHs is the part of the enzymes that most readily exchanges
      electrons with the electrode. However, for P. sordida CDH on 11-mercaptoundecanol
      or dithiopropionic acid-modified Au electrodes, a second voltammetric wave was
      noticed suggesting that for some orientations of the enzyme, DET communication
      with the FAD cofactor can also be obtained.

PMID- 15741071
TI  - An amperometric glucose biosensor prototype fabricated by thermal inkjet
      printing.
AB  - The prototype of an amperometric glucose biosensor was realized by thermal inkjet
      printing using biological and electronic water-based inks, containing a glucose
      oxidase (GOD) from Aspergillus niger and the conducting polymer blend poly(3,4
      ethylenedioxythiophene/polystyrene sulfonic acid) (PEDOT/PSS), respectively. The
      biosensor was fabricated microdepositing PEDOT/PSS and GOD, in sequence, on ITO
      glass, by a commercial inkjet printer, with the help of a commercial software.
      High density microdots matrices were so-realized, with a calculated resolution of
      about 221 x 221 dpi (dot per inch). By means of a rapid and easy assay it was
      demonstrated that no activity loss occurred upon the printing of GOD, despite of
      the use of a thermal printhead. The device was encapsulated in a semipermeable
      membrane of cellulose acetate, applied by dip-coating, in order to prevent
      dissolution of the enzyme and/or PEDOT/PSS in water. The preliminary response of
      the electrode was measured in an aqueous glucose solution in the presence of
      ferrocenemethanol (FeMeOH) as a mediator, and resulted linear up to 60 mM in
      glucose. The best sensitivity value achieved was 6.43 microAM(-1) cm(-2) (447
      nAM(-1) U(-1) cm(-2)). The characteristics of the device, and the possible
      performance improvements have been analyzed and discussed. The reported findings
      indicate that inkjet printing could be a viable instrument for the easy
      construction of a working biosensor via direct digital design using biological
      and conductive polymer based inks. Such an approach may be seen as an example of
      "biopolytronics".

PMID- 15741072
TI  - Investigation of osteoprotegerin interactions with ligands and antibodies using
      piezoelectric biosensors.
AB  - Osteoprotegerin (OPG, osteoclastogenesis inhibitory factor) is a secretory
      glycoprotein involved as a soluble factor in the regulation of bone mass. OPG and
      its ligand (RANKL) levels in serum indicate the osteoclast formation activity.
      Alterations of the RANKL/OPG concentration ratio may be the cause of bone loss in
      many imbalances including osteoporosis, hypercalcaemia, metastatic osteolytic
      lesions and rheumatic bone degradation. The interactions of OPG with several
      antibodies were studied using the piezoelectric quartz crystal sensor. Monoclonal
      anti-OPG antibodies (5H3, 4E6H9 and OPG1.3) were immobilised on the sensing
      surface modified with covalently attached monolayer of protein A. Binding of both
      OPG standard and recombinant OPGFc chimeric protein was followed in real time.
      All antibodies were able to bind OPG and OPGFc, though in the case of MAb 4E6H9
      the immunocomplexes dissociated quickly in the absence of OPG. Alternatively,
      biorecognition layers with RANKL were used. Two versions of the piezoelectric
      sensor for OPG were developed. The direct immunosensor was based on the antibody
      5H3 and the affinity sensor employed the immobilised RANKL. The RANKL sensor
      exhibited poor reproducibility of results. For the immunosensor, the measuring
      range was 1.2-35 U/L of OPG. One analysis was completed within 15 min; the
      sensors were used repeatedly using regeneration with glycine buffer (pH 2.0). The
      developed immunosensor seems promising for rapid determination of osteoprotegerin
      in serum.

PMID- 15741073
TI  - Immunosensor for Mycobacterium tuberculosis on screen-printed carbon electrodes.
AB  - In this work, two methods have been compared to produce enzymatic voltammetric
      immunosensors for the determination of Mycobacterium tuberculosis antigens (Ag360
      and Ag231), using a pre-oxidised screen-printed carbon electrode (SPCE) as a
      signal transduction element. The enzyme alkaline phosphatase (AP) was used in
      combination with the substrate 3-indoxyl phosphate (3-IP). In one design, the
      immune complexes between M. tuberculosis antigens and monoclonal antibodies
      against M. tuberculosis were formed out of the electrode surface. Then, the
      immune complexes were captured by biotinylated rabbit anti-M. tuberculosis
      antibodies, immobilised on the streptavidin modified SPCEs through the
      streptavidin:biotin reaction. Finally, an alkaline phosphatase (AP) labelled
      rabbit IgG anti-mouse immunoglobulin G was used as a detector antibody. In the
      other design, the M. tuberculosis antigens were captured by monoclonal antibodies
      against M. tuberculosis, which were immobilised on the electrode surface through
      the reaction with rabbit IgG passively adsorbed on the SPCEs. The biotinylated
      rabbit anti-M. tuberculosis antibodies were used with an alkaline phosphatase
      labelled streptavidin as detector antibodies. The best results for M.
      tuberculosis antigen determination were obtained using the immunosensor on the
      streptavidin modified SPCEs and the immune complexes between antigen Ag231 and
      monoclonal antibodies MabF184-3, with a detection limit of 1.0 ng/ml. The
      immunosensor was also applied to Ag231 spiked proteic matrices.

PMID- 15741074
TI  - Monitoring complex formation in the blood-coagulation cascade using aptamer
      coated SAW sensors.
AB  - Specific binding of the anticoagulants heparin and antithrombin III to the blood
      clotting cascade factor human thrombin was recorded as a function of time with a
      Love-wave biosensor array consisting of five sensor elements. Two of the sensor
      elements were used as references. Three sensor elements were coated with RNA or
      DNA aptamers for specific binding of human thrombin. The affinity between the
      aptamers and thrombin, measured using the biosensor, was within the same range as
      the value of K(D) measured by filter binding experiments. Consecutive binding of
      the thrombin inhibitors heparin, antithrombin III or the heparin-antithrombin III
      complex to the immobilized thrombin molecules, and binding of a ternary complex
      of heparin, anithrombin III, and thrombin to aptamers was evaluated. The
      experiments showed attenuation of binding to thrombin due to heparin-antithrombin
      III complex formation. Binding of heparin activated the formation of the
      inhibitory complex of antithrombin III with thrombin about 2.7-fold. Binding of
      the DNA aptamer to exosite II appeared to inhibit heparin binding to exosite I.

PMID- 15741075
TI  - Langmuir monolayer approaches to protein recognition through molecular
      imprinting.
AB  - Surface plasmon resonance (SPR) spectroscopy and atomic force microscopy (AFM)
      have been employed to investigate ferritin adsorption to binary surfactant
      monolayers of cationic dioctadecyldimethylammonium bromide (DOMA) and non-ionic
      methyl stearate (SME). Surfactant molar ratios, miscibility, and lateral mobility
      were controlled to define the number, size, and distribution of "binding sites"
      for ferritin, which under the low ionic strength conditions investigated,
      adsorbed to the monolayers predominantly through electrostatic interactions.
      Successive adsorption/desorption cycles revealed that fluid monolayers, capable
      of laterally restructuring during the initial protein adsorption event, bound up
      to 60% more ferritin (dependent on SME:DOMA ratios) as compared to monolayers
      that were immobilized on a hydrophobic support during this first adsorption step.
      The enhanced binding of ferritin to fluid monolayers was accentuated in films
      having non-ionic SME as the principal component. These findings support the
      premise that the surfactants reorganize to form favorable interactions with an
      adsorbing protein, leading to protein specific charge patterns, or templates, in
      the films. Template assessment, however, was complicated by the presence of an
      irreversibly bound protein fraction, which AFM revealed to be locally ordered
      protein clusters.

PMID- 15741076
TI  - Quantitative analysis of the response of an electrochemical biosensor for
      progesterone in milk.
AB  - An electrochemical biosensor for progesterone in cow's milk was developed and
      used in a competitive immunoassay by Hart et al. (1977, Studies towards a
      disposable screenprinted amperometric biosensor for progesterone, Biosens.
      Bioelectron. 12, 1113-1121). The sensor was fabricated by depositing anti
      progesterone monoclonal antibody (mAb) onto screen-printed carbon electrodes
      (SPCEs) which were coated with rabbit anti-sheep IgG (rIgG). This sensor was
      operated following the steps of competitive binding between sample and conjugate
      (alkaline-phosphatase-labelled progesterone) for the immobilised mAb sites and
      measurements of an amperometric signal in the presence of p-nitrophenylphosphate
      using either colorimetric assays or cyclic voltammetry. The hook effect of the
      progesterone biosensor was found in the concentration range of milk progesterone
      between 0 and 5 ng/ml when the sensor was fabricated using a loading of 25 ng
      rIgG per electrode of a diameter of 3 mm and a 1/50 dilution of mAb. A computer
      model has been developed in this study to simulate the operation of this
      progesterone biosensor with consideration of the fabrication processes. This
      paper presents the results of validating the computer model and the model has
      predicted the hook effect as observed in tests. The model thus reveals that the
      hook effect is determined by the total number of binding sites available and the
      rates of labelled and unlabelled progesterone diffusing towards the sensor
      surface and the binding rates.

PMID- 15741077
TI  - In vitro cortical neuronal networks as a new high-sensitive system for biosensing
      applications.
AB  - By taking advantages of the main features of the microelectrode array (MEA)
      technology (i.e. multisite recordings, stable and long-term coupling with the
      biological preparation), we analyzed the changes in activity patterns induced by
      applying specific substances to dissociated cortical neurons from rat-embryos
      (E18). Data were recorded simultaneously from 60 electrodes, and the
      electrophysiological behavior was investigated during the third week in vitro,
      both at the spike and burst level. The analysis of the electrophysiological
      activity modulation, by applying agonists of the ionotropic glutamate receptors
      at low (i.e. 0.2-1-5 microM) and high (i.e. 50-100 microM) concentrations, is
      presented. Preliminary results show that the dynamics of the in vitro cortical
      neurons is very sensitive to pharmacological manipulation of the glutamatergic
      transmission and the effects on the network behavior are strictly dependent from
      the drug concentration. In particular, the addition of a high-dose of agonist
      determined a global and irreversible depression of the network activity, while,
      in the low-concentration case, the electrophysiological behavior showed different
      results, depending on the type of receptor involved. From these observations, we
      are encouraged to think of a more engineered system, based on in vitro cortical
      neurons, as a novel sensitive system for drug (pre)-screening and
      neuropharmacological evaluations.

PMID- 15741079
TI  - Benzene analysis in workplace air using an FIA-based bacterial biosensor.
AB  - A bacterial biosensor based on flow injection analysis (FIA) has been developed
      for the determination of benzene in workplace air samples. Benzene can be used by
      the bacteria Pseudomonas putida ML2 as a sole carbon source, and its aerobic
      degradation can be measured using a dissolved oxygen electrode. The bacterial
      cells were immobilised between two cellulose acetate membranes and fixed onto a
      Clark dissolved oxygen probe, which was inserted into a custom-made flow cell.
      The applicability of the biosensor for the analysis of air samples containing
      benzene was investigated. Air samples were collected from a controlled exposure
      room using charcoal adsorption tubes, and benzene extracted with solvent
      desorption using dimethylformamide (DMF). The biosensor displayed a linear
      detection range between 0.025 and 0.15 mM benzene based on standard solutions
      containing a maximum of 2% DMF, with a response time of 6 min. This linear
      detection range allows the analysis of air containing between 3 and 16 ppm
      benzene based on a 60-min sampling period. DMF proved to be compatible for use
      with the biosensor, causing minimal interference with the sensor response and
      causing no toxic effects on the bacterial cells. The FIA system was easily
      transported to an in situ location, and a correlation was obtained between the
      biosensor and gas chromatography (GC) results for the preliminary air samples
      investigated. Moreover, the biosensor displayed no interference to other benzene
      related compounds in the BTEX range. The results from this work have shown that
      the biosensor has potential applications for the analysis of benzene in workplace
      air samples, with the added advantages over the conventional GC methods of low
      operation costs, ease of use, and portability for in situ measurements.

PMID- 15741078
TI  - Membrane-based on-line optical analysis system for rapid detection of bacteria
      and spores.
AB  - We report here the adaptation of our electronic microchip technology towards the
      development of a new method for detecting and enumerating bacterial cells and
      spores. This new approach is based on the immuno-localization of bacterial spores
      captured on a membrane filter microchip placed within a flow cell. A combination
      of microfluidic, optical, and software components enables the integration of
      staining of the bacterial species with fully automated assays. The quantitation
      of the analyte signal is achieved through the measurement of a collective
      response or alternatively through the identification and counting of individual
      spores and particles. This new instrument displays outstanding analytical
      characteristics, and presents a limit of detection of approximately 500 spores
      when tested with Bacillus globigii (Bg), a commonly used simulant for Bacillus
      anthracis (Ba), with a total analysis time of only 5 min. Additionally, the
      system performed well when tested with real postal dust samples spiked with Bg in
      the presence of other common contaminants. This new approach is highly
      customizable towards a large number of relevant toxic chemicals, environmental
      factors, and analytes of relevance to clinical chemistry applications.

PMID- 15741080
TI  - Cyclic and pulse voltammetric study of dopamine at the interface between two
      immiscible electrolyte solutions.
AB  - The detection of dopamine by differential pulse voltammetry (DPV) and square wave
      voltammetry (SWV) at the interface between two immiscible electrolyte solutions
      (ITIES) has been studied. Voltammetry at the liquid/liquid (water/1,2
      dichloroethane) interface provides a simple method for overcoming the major
      problem associated with dopamine detection by voltammetry at solid electrodes:
      the co-existence of ascorbate at higher concentrations. Selectivity for dopamine
      was achieved by the use of dibenzo-18-crown-6 as an ionophore for the facilitated
      transfer voltammetry of protonated dopamine across the ITIES. Under these
      conditions, ascorbate is not transferred and hence does not interfere in the ion
      transfer current for dopamine. By use of DPV and SWV, the lowest concentration
      detectable can be lowered from ca. 0.1 mM (obtained with cyclic voltammetry) to 2
      microM. Evaluation of the effect of some other physiologically important species
      (acetylcholine, sodium, potassium and ammonium ions) on the dopamine transfer
      voltammetry has been studied, indicating the need for improved ionophore designs
      in order to achieve practically useful selectivity.

PMID- 15741082
TI  - Fabrication and characteristics of MOSFET protein chip for detection of ribosomal
      protein.
AB  - A metal oxide silicon field effect transistor (MOSFET) protein chip for the easy
      detection of protein was fabricated and its characteristics were investigated.
      Generally, the drain current of the MOSFET is varied by the gate potential. It is
      expected that the formation of an antibody-antigen complex on the gate of MOSFET
      would lead to a detectable change in the charge distribution and thus, directly
      modulate the drain current of MOSFET. As such, the drain current of the MOSFET
      protein chip can be varied by ribosomal proteins absorbed by the self-assembled
      monolayer (SAM) immobilized on the gate (Au) surface, as ribosomal protein has
      positive charge, and these current variations then used as the response of the
      protein chip. The gate of MOSFET protein chip is not directly biased by an
      external voltage source, so called open gate or floating gate MOSFET, but rather
      chemically modified by immobilized molecular receptors called self-assembled
      monolayer (SAM). In our experiments, the current variation in the proposed
      protein chip was about 8% with a protein concentration of 0.7 mM. As the protein
      concentration increased, the drain current also gradually increased. In addition,
      there were some drift of the drain current in the device. It is considered that
      these drift might be caused by the drift from the MOSFET itself or protein
      absorption procedures that are relied on the facile attachment of thiol (-S)
      ligands to the gate (Au) surface. We verified the formation of SAM on the gold
      surface and the absorption of protein through the surface plasmon resonance (SPR)
      measurement.

PMID- 15741081
TI  - A new surface plasmon resonance sensor for high-throughput screening
      applications.
AB  - We report a new high-throughput surface plasmon resonance (SPR) sensor based on
      combination of SPR imaging with polarization contrast and a spatially patterned
      multilayer SPR structure. We demonstrate that this approach offers numerous
      advantageous features including high-contrast SPR images suitable for automated
      computer analysis, minimum crosstalk between neighboring sensing channels and
      inherent compensation for light level fluctuations. Applications of a laboratory
      prototype of the high-throughput SPR sensor with 108 sensing channels for
      refractometry and biosensing are described. In refractometric experiments, the
      noise-limited refractive index resolution of the system has been established to
      be 3 x 10(-6) refractive index unit (RIU). Experimental data on detection of
      human choriogonadotropin (hCG) suggest that in conjunction with monoclonal
      antibodies against hCG, the reported SPR imaging sensor is capable of detecting
      hCG at concentrations lower than 500 ng/ml.

PMID- 15741083
TI  - Glutamate detection from nerve cells using a planar electrodes array integrated
      in a microtiter plate.
AB  - There is an increasing interest in new strategies for replacing animal tests in
      research. The use of cell cultures and integrated electrodes is seen as a
      promising alternative that could potentially solve this problem. In this work, we
      present a L-glutamate sensor based on a bienzyme redox hydrogel, capable of
      detecting the release of this excitatory neurotransmitter from adherently growing
      cells upon stimulation. The low working potential required for the operation of
      the sensor decreases the possibility of interference by easily oxidizable
      compounds always present in complex biological samples. A low detection limit of
      0.5 microM L-glutamate, a response time of about 35 s, and a linear range of up
      to 60 microM are the main characteristics of the sensor. The system has been
      successfully employed to monitor the release of l-glutamate from HN10 and C6
      cells upon stimulation with K(+)-ions. The developed integrated electrochemical
      platform will be used in future for drug screening and potentially for replacing
      animal models in neurological experiments.

PMID- 15741084
TI  - A molecular delivery system by using AFM and nanoneedle.
AB  - We developed a new low invasive cell manipulation and gene or molecule transfer
      system in a single living cell by using an atomic force microscope (AFM) and
      ultra thin needle, a nanoneedle. DNA was immobilized on the surface of the
      nanoneedle by covalent bonding and avidin-biotin affinity binding. Immobilization
      of DNA on the nanoneedle was confirmed by measuring the unbinding force between
      avidin and biotin. The DNA-immobilized nanoneedle was successfully inserted into
      HEK293 cells. Though TO-PRO-3 iodide staining experiments using confocal
      microscopy, we observed the immobilized DNA on the surface of the nanoneedle,
      which was retained after 10 times insertions to and evacuations from a living
      cell.

PMID- 15741085
TI  - Dependence of buffer acidity and surfactant chain-length on electro-osmotic
      mobility in thermoplastic microchannels.
AB  - In this paper, we report the dependence of buffer pH and coating surfactant chain
      length on electro-osmotic (EO) mobility in co-polyester microchannels.
      Thermoplastics co-polyester hydrolyzes to anionic functionality to create
      electrical double layer on the micro-channel walls. These negatively charged
      sites are partially or completely screened when long-chain surfactants are added
      into the buffer. This ancillary technique to modify surface charge polarity to
      avoid analyte adsorption is known as dynamic coating. We develop a theory to
      predict the EO mobility tendency on buffer acidity considering the combination of
      pH-dependent surfactant aggregation and surface dissociation. Our findings of pH
      dependent EO mobility in coated channels, using three types of quaternary
      ammonium surfactants, lauryltrimethyammonium bromide (LTAB), trimethyl
      (tetradecyl) ammonium bromide (TTAB), and cetyltrimethyammonium bromide (CTAB),
      agree with our theoretical prediction. We also explain the chain-length
      dependence of mobility with a collaborative adsorption mechanism of surfactant
      aggregates.

PMID- 15741086
TI  - Frequency bandwidth limitation of external pulse electric fields in cylindrical
      micro-channel electrophoresis with analyte velocity modulation.
AB  - In capillary electrophoresis, effective optical signal quality improvement is
      obtained when high frequency (>100 Hz) external pulse fields modulate analyte
      velocities with synchronous lock-in detection. However, the pulse frequency is
      constrained under a critical value corresponding to the time required for the
      bulk viscous flow, which arises due to viscous momentum diffusion from the
      electro-osmotic slip in the Debye layer, to reach steady-state. By solving the
      momentum diffusion equation for transient bulk flow in the micro-channel, we show
      that this set-in time to steady-state and hence, the upper limit for the pulse
      frequency is dependent on the characteristic diffusion length scale and therefore
      the channel geometry; for cylindrical capillaries, the set-in time is
      approximately one half of that for rectangular slot channels. From our estimation
      of the set-in time and hence the upper frequency modulation limit, we propose
      that the half width of planar channels does not exceed 100 microm and that the
      radii of cylindrical channels be limited to 140 microm such that there is a
      finite working bandwidth range above 100 Hz and below the upper limit in order
      for flicker noise to be effectively suppressed.

PMID- 15741087
TI  - Optical microsensors for pesticides identification based on porous silicon
      technology.
AB  - A simple and low cost optical sensor, based on porous silicon nanotechnology, has
      been used to detect and quantify the presence of atrazine pesticide in water and
      humic acid solutions. In both cases, a well defined optical signal variation can
      be registered, even at low concentration as 1 ppm. The phenomenon can be ascribed
      to the capillary infiltration of liquid into the pores, which changes the average
      refractive index of the structure. Due to the resonant cavity enhanced operation
      of the proposed sensors, very low detection limits can be reached.

PMID- 15741088
TI  - Study of carbon nanotube modified biosensor for monitoring total cholesterol in
      blood.
AB  - A carbon nanotube modified biosensor for monitoring total cholesterol in blood
      was studied. This sensor consists of a carbon working electrode and a reference
      electrode screen-printed on a polycarbonate substrate. Cholesterol esterase,
      cholesterol oxidase, peroxidase and potassium ferrocyanide were immobilized on
      the screen-printed carbon electrodes. Multi-walled carbon nanotubes (MWCN) were
      added to prompt electron transfer. Experimental results show that the carbon
      nanotube modified biosensor offers a reliable calibration profile and stable
      electrochemical properties.

PMID- 15741089
TI  - Development of a novel glucose enzyme fuel cell system employing protein
      engineered PQQ glucose dehydrogenase.
AB  - Glucose dehydrogenase harboring pyrroloquinoline quinone as the prosthetic group
      (PQQGDH) from Acinetobacter calcoaceticus is an ideal enzyme for the anode of
      biofuel cell, because of its oxygen insensitivity and high catalytic efficiency.
      However, the application of PQQGDH for the bioanode is inherently limited because
      of its instability. Using Ser415Cys mutant whose stability was greatly improved,
      we constructed the biofuel cell system employing the engineered PQQGDH as the
      bioanode enzyme and bilirubin oxidase (BOD) as the biocathode, and compared the
      stability of the biofuel cell with that employing wild-type PQQGDH. The maximum
      power density was 17.6 microW/cm2 at an external optimal load of 200 k omega.
      Using Ser415Cys mutant, the lifetime of the biofuel cell system was greatly
      extended to 152 h, more than six times as that of the biofuel cell employing the
      wild-type.

PMID- 15741090
TI  - Impedimetric immunosensors based on the conjugated polymer PPV.
AB  - In the work reported here, we investigated the interaction between the
      semiconducting polymer MDMO-PPV and antibodies against the fluorescent dyes
      fluorescein isothiocyanate (FITC) and Cy5. The antibodies are adsorbed physically
      onto thin polymer films on gold electrodes, as seen in AFM images of these films.
      By tuning the antibody concentration, the contact angle of distilled water with
      the film can be made to vary between 95 degrees and 50 degrees, showing that
      different surface densities of antibody can be obtained. That these biosensor
      films specifically bind their antigenic fluorescent molecules from PBS buffer
      solution is demonstrated by confocal fluorescence microscopy. Specific antigen
      antibody recognition is demonstrated by lack of cross-sensitivity between the two
      antibodies and their antigens. In a biosensor prototype based on differential
      impedance spectroscopy, these polymer films show a clear response to 1 ppb
      antigen solution, with a time constant of 2-3 min.

PMID- 15741091
TI  - Immunoassay of prostate-specific antigen (PSA) using resonant frequency shift of
      piezoelectric nanomechanical microcantilever.
AB  - We designed and fabricated the nanomechanical Pb(Zr0.52Ti0.48)O3 (PZT)
      cantilever; we demonstrated a novel electrical measurement, under a controlled
      ambient temperature and humidity, for label-free detection of a prostate-specific
      antigen (PSA); and we achieved a detection sensitivity as low as 10 pg/ml. For
      the fabrication of our nanomechanical PZT cantilevers, we used composite layers
      of Ta/Pt/PZT/Pt/SiO2 on a SiN(x) supporting layer for electrical self-sensing
      without external oscillators. This method allows PSA proteins to be detected via
      a simple electrical measurement of the resonant frequency change generated by the
      molecular interaction of the antigen (Ag) and the antibody (Ab). The resonant
      frequency shifted due to the specific binding of the PSA Ag to its Ab which is
      immobilized via calixcrown self-assembled monolayers on an Au surface deposited
      on a nanomechanical PZT cantilever. We determined the resonant frequency shift as
      the value of -172 Hz and -273 Hz, when the concentration of PSA Ag was 1 ng/ml,
      with the cantilever dimensions of 100 microm x 300 microm and 50 microm x 150
      microm, respectively. Theoretical and experimental analysis suggests that the
      minimum detectable sensitivity for a resonant frequency shift due to a PSA Ag-Ab
      interaction depends on the dimensions of the nanomechanical PZT cantilever. These
      results also demonstrate that the experimentally measured resonant frequency
      shift is larger than that calculated theoretically due to the compressive stress
      of the PSA Ag-Ab interaction.

PMID- 15741092
TI  - A molecularly imprinted polymer on indium tin oxide and silicon.
AB  - Molecular imprinting is a technique for creating artificial receptor sites in a
      polymer. Molecularly imprinted polymers (MIPs) are produced by forming a polymer
      around a molecule that is used as the template. Upon removal of the template,
      molecular holes remain which are specific in shape and size to the target
      molecule. In this research, a MIP was formed for theophylline using a copolymer
      of methacrylic acid and ethylene glycol dimethacrylate. The theophylline MIP was
      formed on two platforms: indium tin oxide (ITO) and silicon, which were used as
      the working electrode for cyclic voltammetry measurements. The presence of
      theophylline was measured using cyclic voltammetry and corresponded to the peak
      current on the cyclic voltammograms. The results of this research agreed with
      previous results of MIPs immobilized on an ITO platform. The peak currents of the
      MIP in the presence and absence of theophylline were compared to the blank
      polymer for each platform. The ratio of peak currents on ITO increased by a
      factor of 9.5 for the MIP compared to the non-imprinted polymer. Similarly, the
      ratio of peak currents on silicon increased by a factor of 6 compared to the non
      imprinted polymer. This research demonstrated a procedure for evaluating a MIP
      layer on two different platforms.

PMID- 15741093
TI  - Novel electrochemical sensor system for protein using the aptamers in sandwich
      manner.
AB  - Novel electrochemical detection system for protein in sandwich manner using the
      aptamers was developed. Two different aptamers, which recognize different
      positions of thrombin, were chosen to construct sandwich type sensing system for
      protein, and one was immobilized onto the gold electrode for capturing thrombin
      onto the electrode and the other was used for detection. To obtain the signal,
      the aptamer for detection was labeled with pyrroquinoline quinone glucose
      dehydrogenase ((PQQ)GDH), and the electrical current, generated from glucose
      addition after the formation of the complex of thrombin, gold immobilized aptamer
      and the (PQQ)GDH labeled aptamer on the electrode, was measured. The increase of
      the electric current generated by (PQQ)GDH was observed in dependent manner of
      the concentration of thrombin added, and more than 10nM thrombin was detected
      selectively. The batch type protein sensing system was constructed using the two
      different aptamers sandwiching thrombin and it showed linear response to the
      increase of the thrombin concentration in the range of 40-100 nM.

PMID- 15741094
TI  - Colloidal quantum dots initiating current bursts in lipid bilayers.
AB  - The combination of inorganic semiconductor nanocrystals, also called quantum dots
      (QDs), with biological materials has recently attracted considerable interest
      since the QDs can be used as superior fluorescent labels. Here, we report on CdSe
      QD initiated current bursts in lipid bilayer membranes on application of a bias
      voltage. The current bursts observed resemble those produced by the peptaibol
      class of antibiotics such as alamethicin and trichorzins. The current
      fluctuations are dependent on the bias voltage and on the concentration of the QD
      applied to the membrane. Our data suggest that QDs with intrinsic dipole moments
      similar to alamethicin can be controlled by an external electric field, which
      creates a torque resulting in the insertion into the lipid membrane.

PMID- 15741095
TI  - Real-time optical biosensor based on differential phase measurement of surface
      plasmon resonance.
AB  - We report a real-time differential phase measurement technique which can be
      implemented in optical surface plasmon resonance biosensors. The important
      feature of our design is that sensitivity has been greatly improved by measuring
      the differential phase change between the s and p-polarizations. Real-time
      measurement capability is achieved by using a phase extracting routine which
      continuously monitors the waveforms captured by two photo-detectors. Measurement
      capability of our setup is demonstrated through real-time monitoring of bovine
      serum albumin (BSA)/anti-BSA binding reaction. The estimated sensitivity of our
      current setup is 7.4 ng/ml.

PMID- 15741096
TI  - From MEMS to NEMS with carbon.
AB  - Our work in carbon-microelectromechanical systems (C-MEMS) suggests that C-MEMS
      might provide a very interesting material and microfabrication approach to
      battery miniaturization, active DNA arrays and a wide variety of chemical and
      biological sensors. In C-MEMS, photoresist is patterned by photolithography and
      subsequently pyrolyzed at high-temperatures in an oxygen-free environment. We
      established that it is possible to use C-MEMS to create very high-aspect ratio
      carbon structures (e.g. posts with an aspect ratio >10), suspended carbon plates
      and suspended carbon nanowires (C-NEMS). By changing the lithography conditions,
      soft and hard baking times and temperatures, additives to the resist, pyrolysis
      time, temperature and environment, C-MEMS permits a wide variety of interesting
      new MEMS and NEMS applications that employ structures having a wide variety of
      shapes, resistivities and mechanical properties. We also demonstrate that arrays
      of high-aspect ratio carbon posts can be charged/discharged with Li and this
      enables the fabrication of a smart switchable array of batteries.

PMID- 15741097
TI  - Study on structure and characterization of inclusion complex of gossypol/beta
      cyclodextrin.
AB  - The inclusion complex of beta-cyclodextrin with gossypol was synthesized by using
      a convenient method of microwave irradiation. The structure of the complex was
      determined by 1H NMR, IR spectroscopy, and as well as the elemental analysis; the
      thermal stability was studied by means of differential thermal analysis (DTA) and
      thermogravimetric analysis (TGA). The association constant between gossypol and
      beta-cyclodextrin measured via UV spectroscopy was 4462M(-1) at room temperature,
      following stoichiometry 1:2.

PMID- 15741098
TI  - Preparation of Z-L-Phe-OH-NBD imprinted microchannel and its molecular
      recognition study.
AB  - An integrated microchip was presented for selective recognition of Z-L-Phe-OH
      NBD, using molecular imprinting technique. Molecularly imprinted polymer (MIP)
      were prepared by copolymerization in the presence of template molecule Z-L-Phe-OH
      NBD, in which methacrylic acid and 4-vinylpyridine were used as functional
      monomers and ethylene dimethacrylate used as crosslinker. Imprinted polymer
      particles were introduced into a microchannel fabricated with a new material i.e.
      poly(methylvinylsiloxane) by simply rapid prototyping method. Imprinted effects
      were evaluated by laser-induced fluorescence (LIF) detection where the results
      indicated that good selective recognition for Z-L-Phe-OH-NBD in the imprinted
      polymer was obtained; the adsorption percentage of Z-L-Phe-OH-NBD was 61%. In
      contrast to conventional molecular imprinting analysis, integration shortened
      overall analysis time from 4h to 10 min.

PMID- 15741099
TI  - Determination of myoglobin based on its enzymatic activity by stopped-flow
      spectrophotometry.
AB  - A new method has been developed for the determination of myoglobin (Mb) based on
      its enzymatic activity for the oxidation of o-phenylenediamine (OPDA) with
      hydrogen peroxide. Stopped-flow spectrophotometry was used to study the kinetic
      behavior of the oxidation reaction. The catalytic activity of Mb was compared to
      other three kinds of catalyst. The time dependent absorbance of the reaction
      product, 2,3-diamimophenazine (DAPN), at a wavelength of 426 nm was recorded. The
      initial reaction rate obtained at 40 degrees C was found to be proportional to
      the concentration of Mb in the range of 1.0 x 10(-6) to 4.0 x 10(-9)mol L(-1).
      The detection limit of Mb was found to be 9.93 x 10(-10)mol L(-1). The relative
      standard deviations were within 5% for the determination of different
      concentrations of Mb. Excess of bovine serum albumin (BSA), Ca(II), Mg(II),
      Cu(II), glucose, caffeine, lactose and uric acid did not interfere.

PMID- 15741100
TI  - Absorption spectroscopic study of synergistic extraction of praseodymium with
      benzoyl acetone in presence of crown ether.
AB  - The extraction behaviour of Pr(III) from aqueous nitric acid medium employing
      benzoylacetone has been studied in presence of two crown ethers, viz., 15-crown-5
      and benzo-15-crown-5 in chloroform medium using UV-vis absorption spectroscopy.
      The binary equilibrium constant (logk(ex)) for the complex
      [Pr(benzoylacetonate)(NO3(-))2(H(2)O)] in organic phase was found to be 1.170.
      The overall equilibrium constants (logK) for the ternary species
      [Pr(benzoylacetonate)(crown ether)(NO3(-))(2)] were estimated to be 4.01 and 4.41
      for 15-crown-5 and benzo-15-crown-5, respectively. The trend in the equilibrium
      constant values were very much in accordance with the nature of substitution of
      the donor moiety. The extraction of Pr(III) by the benzoylacetone-crown ether
      combination was maximum at pH 3.0 and extraction decreases with increase in pH.
      It has been found that the extent of extraction of Pr(III) in organic phase as
      the binary as well as ternary complex [Pr(benzoylacetonate)(NO3(-))(2)(H(2)O)]
      and [Pr(benzoylacetonate)(crown ether)(NO3(-))(2)] increases with increase in
      concentration of the ligand. Similar trend is observed in the extraction by only
      donors. Enthalpies and entropies of formation for the ternary extraction process
      have been estimated. In addition, the effect of NaNO(3) as foreign salt was also
      studied and it was observed that with increase in ionic strength, percentage
      extraction increases.

PMID- 15741101
TI  - Design, synthesis and characterization of a novel fluorescent probe for nitric
      oxide based on difluoroboradiaza-s-indacene fluorophore.
AB  - Nitric oxide (NO) is a gaseous, free radical, which plays a role as an
      intracellular second messenger and a diffusible intercellular messenger. To
      obtain evidence for NO function in vivo, 1,3,5,7-tetramethyl-8-(4'-aminophenyl-N
      (2''-amino)-phenzyl)-difluoroboradiaza-s-indacene (TMAPABODIPY) was designed and
      synthesized as a fluorescent probe for nitric oxide, which features high
      photostability and no pH dependency over a wide pH range. The fluorescence of
      TMAPABODIPY itself is very strong. When TMAPABODIPY traps NO in the presence of
      dioxygen, the weak fluorescent triazole form is obtained, which offers the
      advantages of specificity, and sensitivity for direct detection of NO. The
      relationship was obtained between the quenching fluorescence intensity and NO
      concentration in the range 0.02-4.0 micromol l(-1). The detection limit is 5 nmol
      l(-1) (S/N = 3). The proposed method has been used to monitor the release of NO
      from S-nitrosocysteine, a NO-releasing agent.

PMID- 15741102
TI  - 1H NMR study of inclusion compounds of phenylurea derivatives in beta
      cyclodextrin.
AB  - Proton nuclear magnetic resonance spectroscopy ((1)H NMR), which has become an
      important tool for the study "in situ" of beta-cyclodextrin (beta-CD) complexes,
      was used to study and structurally characterize the inclusion complexes formed
      between beta-CD and isoproturon, fenuron, monuron and diuron. The high variation
      of the chemical shifts from the proton located inside the cavity (H-3, H-5 and H
      6) coupled with the non variation of the one located outer sphere of the beta-CD
      (H-1, H-2 and H-4) provided clear evidence of the inclusion phenomena. Two
      dimensional rotating frame Overhauser effect spectroscopy (ROESY) experiments
      were carried out to further support the proposed inclusion mode.

PMID- 15741103
TI  - Mixed ligand complexes of bis(phenylimine) Schiff base ligands incorporating
      pyridinium moiety Synthesis, characterization and antibacterial activity.
AB  - The synthesis and structural characterization of mixed ligand complexes derived
      from 2,6-pyridinedicarboxaldehydebis(o-hydroxyphenylimine), 2,6
      pyridinedicarboxaldehydebis(p-hydroxyphenylimine) (1(ry) ligands) and 2
      aminopyridne (2(ry) ligand) are reported. The ligands and their transition metal
      complexes were characterized on the bases of their elemental analyses, IR, solid
      reflectance, magnetic moment, molar conductance and thermal analysis (TGA). The
      mixed ligand complexes are formed in the 1:1:1 (M:L(1) or L(2):L') ratio as found
      from the elemental analyses and found to have the formulae [MX(2)(L(1) or
      L(2))(L')].nH(2)O where M = Co(II), Ni(II), Cu(II) and Zn(II), L(1) = 2,6
      pyridinedicarboxaldehydebis(p-hydroxyphenylimine), L(2) = 2,6-pyridine
      dicarboxaldehydebis(o-hydroxyphenylimine), L' = 2-aminopyridine, X = Cl(-) in
      case of Cu(II) complex and Br(-) in case of Co(II), Ni(II) and Zn(II) complexes
      and y = 0-3. The molar conductance data reveal that the chelates are non
      electrolytes. IR spectra show that the Schiff bases are coordinated to the metal
      ions in a terdentate manner with NNN donor sites of the pyridine-N and two
      azomethine-N. While 2-aminopyridine coordinated to the metal ions via its
      pyridine-N. Magnetic and solid reflectance spectra are used to infer the
      coordinating capacity of the ligand and the geometrical structure of these
      complexes are found to be octahedral. The thermal behaviour of these chelates
      shows that the hydrated water molecules and the anions are removed in a
      successive two steps followed immediately by decomposition of the ligands (L(1),
      L(2) and L') in the subsequent steps. The activation thermodynamic parameters,
      such as, E*, DeltaH*, DeltaS* and DeltaG* are calculated from the TG curves and
      discussed. The ligands and their metal chelates have been screened for their
      antimicrobial activities and the findings have been reported, explained and
      compared with some known antibiotics.

PMID- 15741104
TI  - Radiative electronic energy transfer-time studies of naphthalene-biacetyl system
      by one and two-photon excitation, and optical antenna mechanism.
AB  - In principle, the optical energy absorbed by a complex molecule raises that
      molecule to one of its excited states, and afterwards this excitation energy
      decays through the relaxation channels. Initially, electronically excited
      naphthalene emits photons and these emitted photons are absorbed by the acceptor
      molecule biacetyl, then excited biacetyl fluoresces. In this investigation
      radiative energy transfer-time is measured in cyclohexane by one and two-photon
      excitations. The UV-vis spectrum of biacetyl vapor at room temperature conditions
      was broad and structureless.

PMID- 15741105
TI  - Vibrational frequencies and structural determinations of divinyl sulfoxide.
AB  - We present a detailed analysis of the structure and infrared spectra of divinyl
      sulfoxide. The vibrational frequencies of the divinyl sulfoxide molecule were
      analyzed using standard quantum chemical techniques. Frequencies were calculated
      at the MP2 and DFT levels of theory using the standard 6-311G* basis set. The
      molecule exists normally in a C(s) configuration. High-energy forms of divinyl
      sulfoxide with C(S) and C(1) symmetries also exist.

PMID- 15741106
TI  - Structural, spectroscopic and thermal characterization of 2-tert
      butylaminomethylpyridine-6-carboxylic acid methylester and its Fe(III), Co(II),
      Ni(II), Cu(II), Zn(II) and UO(2)(II) complexes.
AB  - Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and UO(2)(II) complexes with the ligand 2
      tert-butylaminomethylpyridine-6-carboxylic acid methylester (HL(2)) have been
      prepared and characterized by elemental analyses, molar conductance, magnetic
      moment, thermal analysis and spectral data. 1:1 M:HL(2) complexes, with the
      general formula [M(HL(2))X(2)].nH(2)O (where M = Co(II) (X = Cl, n = 0), Ni(II)
      (X = Cl, n = 3), Cu(II) (grey colour, X = AcO, n = 1), Cu(II) (yellow colour, X =
      Cl, n = 0) and Zn(II) (X = Br, n = 0). In addition, the Fe(III) and UO(2)(II)
      complexes of the type 1:2 M:HL(2) and with the formulae [Fe(L(2))(2)]Cl and
      [UO(2)(HL(2))(2)](NO(3))(2) are prepared. From the IR data, it is seen that HL(2)
      ligand behaves as a terdentate ligand coordinated to the metal ions via the
      pyridyl N, carboxylate O and protonated NH group; except the Fe(III) complex, it
      coordinates via the deprotonated NH group. This is supported by the molar
      conductance data, which show that all the complexes are non-electrolytes, while
      the Fe(III) and UO(2)(II) complexes are 1:1 electrolytes. IR and H1-NMR spectral
      studies suggest a similar behaviour of the Zn(II) complex in solid and solution
      states. From the solid reflectance spectral data and magnetic moment
      measurements, the complexes have a trigonal bipyramidal (Co(II), Ni(II), Cu(II)
      and Zn(II) complexes) and octahedral (Fe(III), UO(2)(II) complexes) geometrical
      structures. The thermal behaviour of the complexes is studied and the different
      dynamic parameters are calculated applying Coats-Redfern equation.

PMID- 15741107
TI  - Growth and spectroscopic characterization of a new organic nonlinear optical
      crystal--8-hydroxyquinoline.
AB  - A novel organic nonlinear optical crystal 8-hydroxyquinoline having good optical
      quality has been grown by slow evaporation solution technique using methanol as
      solvent. The morphology of the grown crystals were identified by X-ray
      diffraction method. Solubility studies were made under various solvents and
      solvent mixtures at different temperatures. Functional groups present in the
      grown material have been identified using FTIR and FT Raman spectra. Transparency
      was tested using UV-vis spectrophotometer and the second harmonic generation was
      also verified.

PMID- 15741108
TI  - Calculation of the fine structure and intensity of the singlet-triplet
      transitions in the imidogen radical.
AB  - The singlet-triplet transition moments are calculated for the NH radical by
      multiconfiguration self-consistent field (MCSCF) method with a quadratic response
      (QR) technique. The band systems in the visible region (b(1)Sigma(+)-->X(3)Sigma(
      ) and a(1)Delta-->X(3)Sigma(-)) of the NH radical are analyzed in comparison with
      previous ab initio treatments and with the recent experimental data in attempt to
      solve some discrepancies. The b(1)Sigma(+)-->X(3)Sigma(Omega)(-) transition
      moments ratio for the two spin sublevels Omega = 1 and Omega=0 of the ground
      state is well reproduced and the radiative lifetime of the b(1)Sigma(+) state
      (tau(b)=58 ms) is obtained in a good agreement with the experimental value
      tau(b)=53((-13)(+17)) ms. The A(3)Pi<--a(1)Delta transition probability is
      calculated for the first time and found to be in an excellent agreement with the
      recent optical pumping measurements of the NH radical in a molecular beam, where
      population transfer from the metastable a(1)Delta state to the ground X(3)Sigma(
      ) state is achieved. For the a(1)Delta-->X(3)Sigma(-) transition some improvement
      is achieved in comparison with the previous ab initio results, but the calculated
      radiative lifetime (tau(a)=3.9 s) is still much lower than the recent measurement
      provides (tau(a)=12.5 s). The zero field splitting and spin-rotation coupling
      constants are calculated for the ground state by different methods and advantage
      of the density functional theory is stressed.

PMID- 15741109
TI  - Physical and spectroscopic studies on novel vanadyl complexes of some substituted
      thiosemicarbazides.
AB  - Complexes of V(IV)O with N(4) ethyl and/or phenyl thiosemicarbazides have been
      prepared to study the role of substituents, on the two sides of thiosemicarbazide
      moiety, on the behavior of the complex formation. The study of ligands in
      solution reflected the dependence of their ionization values on the nature of the
      function groups neighboring the active sites. Two main (octahedral and square
      pyramid) structures have been characterized for the solid complexes by the well
      known methods. There is some similarity between the structure and the color of
      the obtained complexes. Three modes of chelation were suggested for the
      investigated complexes. Complete disappearance of the nitrile group during the
      complex formation with cyano ligands is attributed to the promotion of water
      molecules to the cyano group. The intensity and position of the VO band in the IR
      spectra reflect not only the nature of the ligand but also the geometry of the
      complex formed. Some complexes were isolated as binuclear and confirmed by ESR
      spectra. The end product on thermal degradation of most complexes was VO(2).

PMID- 15741110
TI  - Investigation of H-bonds in 1,1-diphenylethanol by IR spectra measurements.
AB  - The parameters of stretching vibrations nu(OH) (frequencies and integral
      intensities) have been calculated from IR spectra of a large number of H
      complexes of 1,1-diphenylethanol [(C(6)H(5))(2)C(CH(3))OH] with solvents of
      various proton accepting strength which were not regularly reported. The data has
      been used to estimate the formation enthalpies of H-complexes and the proton
      donor action of the mentioned alcohol. Also, correlations between those spectral
      characteristics have been investigated. The H-bonds in 1,1-diphenylethanol (DPE)
      have been investigated depending on concentrations in CCl(4) and temperature by
      means of infrared (IR) absorption spectra measurements. It has been found that
      the hydrogen bonds of the crystalline DPE are formed in the manner of cyclic
      tetramer, while in solutions with the concentration 0.5 mol/l, cyclic dimers are
      formed, which in higher concentrations change into cyclic tetramers.

PMID- 15741111
TI  - Time-resolved photocurrent generation in a photoelectrochemical cell with
      phthalocyanine.
AB  - The kinetics of photocurrent generated in the photoelectrochemical cell (PEC)
      with phthalocyanine (Pc) dyes in the microsecond time scale was discussed. The
      shape of the kinetics is rather complex and it was discussed in terms of
      molecular phenomena and electrochemical processes occurring after laser flash
      illumination. Time constants were calculated from the photocurrent decay curves
      and at least three time components were well recognized (rise in 0.40 micros,
      declining in 0.40-0.45 micros and secondary increase in about 2 micros). The
      shape of the kinetics was discussed in terms of dye singlet and triplet state
      participation in photocurrent generation and also in terms of creation of the
      Helmholtz-Goy double layer at the dye layer-semiconductor interface. The
      alteration in shape of the Helmholtz-Goy double layer in photoelectrochemical
      cell after laser pulse was also discussed.

PMID- 15741112
TI  - Solvatochromism of 3-[2-(4-diphenylaminophenyl)benzoxazol-5-yl]alanine methyl
      ester. A new fluorescence probe.
AB  - The photophysical properties of 3-[2-(4-diphenylaminophenyl)benzoxazol-5
      yl]alanine methyl ester (1b) and its Boc derivative (1a) were studied in a series
      of solvents. Its UV-Vis absorption spectra are less sensitive to the solvent
      polarity than the corresponding fluorescence spectra which show pronounced
      solvatochromic effect leading to large Stokes shifts. Using an efficient
      solvatochromic method, based on the molecular-microscopic empirical solvent
      polarity parameter E(T)(N), a large change of the dipole moment on excitation has
      been found. From an analysis of the solvatochromic behaviour of the UV-Vis
      absorption and fluorescence spectra in terms of bulk solvent polarity functions,
      f(epsilon(r),n) and g(n), a large excited-state dipole moment (mu(e) = 11D),
      almost perpendicular to the smaller ground-state dipole moment, was observed.
      This demonstrates the formation of an intramolecular charge-transfer excited
      state. Large changes of the fluorescence quantum yields as well as the
      fluorescence lifetimes with an increase of a solvent polarity cause that the new
      non-proteinogenic amino acid, 3-[2-(4-diphenylaminophenyl)benzoxazol-5-yl]
      alanine methyl ester, is a new useful fluorescence probe for biophysical studies
      of peptides and proteins.

PMID- 15741113
TI  - Surface-enhanced Raman scattering and density functional theory calculation of
      uracil on gold and silver nanoparticle surfaces.
AB  - The adsorption structure of uracil on gold and silver nanoparticle surfaces has
      been comparatively studied by means of surface-enhanced Raman scattering (SERS).
      Uracil appeared to assume a perpendicular orientation with respect to the
      surfaces. The presence of the nu(CH) band in the SERS spectra indicated a
      vertical orientation of the aromatic ring of uracil on Au and Ag. The density
      functional theory (DFT) calculation was performed at the levels of B3LYP and MP2
      to estimate the energetic stability of the N3- and N1-deprotonated tautomers and
      their vibrational frequencies on the surfaces. Almost all the vibrational bands
      in the SERS spectra at high concentrations could be ascribed to the N3
      deprotonated uracil. The N3-deprotonated tautomer was predicted to be more
      favorable on Au than on Ag from the DFT calculation. The metal-N bond distance
      was assumed to be shorter for Au than for Ag upon adsorption of uracil.

PMID- 15741114
TI  - Time-resolved electron paramagnetic resonance of the lowest excited triplet state
      of phenazinium cation.
AB  - Time-resolved and steady-state electron paramagnetic resonance (EPR) spectra have
      been observed for the lowest excited triplet (T(1)) states of phenazine (Phz) and
      its singly protonated cation (phenazinium) in sulfuric acid-ethanol mixtures at
      77K. The single protonation appears to have little effect on the anisotropic
      sublevel populating rates of the T(1) state of phenazine. However, the zero-field
      splitting (ZFS) parameter D decreases on the protonation, reflecting the increase
      of delocalization of the two unpaired electrons. The sublevel preferentially
      populated by intersystem crossing (ISC) is T(y) in both phenazine and phenazinium
      (the y-axis is parallel to the in-plane long axis). From the analysis of the
      observed anisotropy in the ISC rates and the semi empirical molecular orbital
      calculations of the ZFS parameters, we concluded that the T(1) state of
      phenazinium is the (3)A(1)(pipi*) state.

PMID- 15741115
TI  - Phase transition affects energy transfer efficiency in phospholipid vesicles.
AB  - The fluorescence quenching of 6-propionyl-2-dimethylaminonaphtalene (PRODAN) and
      6-dodecanoyl-2-dimethylaminonaphtalene (LAURDAN) by octadecyl rhodamine B (ORB)
      in a model system of small unilamellar vesicles (SUV) of dipalmitoylphosphatidyl
      choline (DPPC) was investigated. Non-linear Stern-Volmer behaviour was observed
      in both systems in the gel phase (25 degrees C) and in the fluid phase (50
      degrees C), resulting from association processes and from static quenching. The
      relative quenching efficiencies of both dyes depend on the phase state of the
      bilayer and indicate a deeper incorporation of PRODAN and LAURDAN into the
      membrane in its fluid phase than in its gel phase.

PMID- 15741116
TI  - Structural model of dioxouranium(VI) with hydrazono ligands.
AB  - Synthesis and characterization of several new coordination compounds of
      dioxouranium(VI) heterochelates with bidentate hydrazono compounds derived from 1
      phenyl-3-methyl-5-pyrazolone are described. The ligands and uranayl complexes
      have been characterized by various physico-chemical techniques. The bond lengths
      and the force constant have been calculated from asymmetric stretching frequency
      of OUO groups. The infrared spectral studies showed a monobasic bidentate
      behaviour with the oxygen and hydrazo nitrogen donor system. The effect of
      Hammett's constant on the bond distances and the force constants were also
      discussed and drawn. Wilson's matrix method, Badger's formula, Jones and El
      Sonbati equations were used to determine the stretching and interaction force
      constant from which the UO bond distances were calculated. The bond distances of
      these complexes were also investigated.

PMID- 15741117
TI  - Photophysical processes of a fluorene derivative containing carbazole unit.
AB  - The photoluminescence properties of 9,9-bis[4'-(9''
      carbazovinylene)phenyl]fluorene (F-CZV) formed by Heck reaction of 9,9-bis(4'
      iodophenyl)fluorene (F-IP) and N-vinylcarbazole have been carefully studied. The
      results show that the compound emits blue light and the dimolecular excimer is
      formed with gradual increase in concentration of F-CZV. The results also indicate
      the interaction between F-CZV and electron donors (N,N-dimethylaniline) or
      electron acceptors (dimethylterephthalate, fullerene carbon nanotubes) can be
      efficiently generated where the processes follow the Stern-Volmer equation.
      Moreover, when dimethylterephthalate (DMTP) or carbon nanotubes (CNTs) is
      gradually added into the solution of F-CZV, the emission intensities of
      fluorescence are unusually increased. But when concentration of
      dimethylterephthalate or carbon nanotubes beyond a certain scope, the emission
      intensities of fluorescence are gradually decreased.

PMID- 15741118
TI  - Magnetic, electronic and electrochemical studies of mono and binuclear Cu(II)
      complexes using novel macrocyclic ligands.
AB  - A series of new mono and binuclear copper (II) complexes [Cul]X(2)and
      [Cu(2)lX(2)] where 1 = L(1), L(2) and L(3) are the macrocyclic ligands. In
      mononuclear complexes the geometry of Cu(II) ion is distorted squareplanar and in
      binuclear complexes the geometry of Cu(II) is tetragonal. The synthesized
      complexes were characterized by spectroscopic (IR,UV-vis and ESR) techniques.
      Electrochemical studies of the complexes reveals that all the mononuclear Cu(II)
      complexes show a single quasireversible one-electron transfer reduction wave
      (E(pc) = -0.76 to -0.84V) and the binuclear complexes show two quasireversible
      one electron transfer reduction waves (E(pc)(1) = -0.86 to -1.01V, E(pc)(2) = 
      1.11 to -1.43V) in cathodic region. The ESR spectra of mononuclear complexes show
      four lines with nuclear hyperfine splittings with the observed g(11) values in
      the ranges 2.20-2.28, g( perpendicular) = 2.01-2.06 and A(11) = 125-273. The
      binuclear complexes show a broad ESR spectra with g = 2.10-2.11. The room
      temperature magnetic moment values for the mononuclear complexes are in the range
      [mu(eff) = 1.70-1.72BM] and for the binuclear complexes the range is [mu(eff) =
      1.46-1.59BM].

PMID- 15741119
TI  - Spectroscopic studies on Co(II), Ni(II) and Cu(II) complexes with a new
      macrocyclic ligand: 2,9-dipropyl-3,10-dimethyl-1,4,8,11-tetraaza-5,7:12,14
      dibenzocyclotetradeca-1,3,8,10-tetraene.
AB  - Cobalt(II), nickel(II) and copper(II) complexes containing a tetradentate
      macrocyclic nitrogen donor ligand i.e. 2,9-dipropyl-3,10-dimethyl-1,4,8,11
      tetraaza-5,7:12,14-dibenzocyclotetradeca-1,3,8,10-tetraene have been synthesized
      and characterized by elemental analysis, molar conductance, magnetic moments,
      mass, (1)H NMR, IR, electronic and EPR spectral studies. All the complexes are of
      high spin type and possess four-coordinated tetrahedral, five-coordinated square
      pyramidal and six-coordinated octahedral/tetragonal geometry. The ligand and its
      metal complexes were also screened against the growth of some bacteria and plant
      pathogenic fungi in vitro.

PMID- 15741120
TI  - Study of EPR, optical properties and electrical conductivity of vanadyl doped
      Bi2O3.PbO.B2O3 glasses.
AB  - Heavy metal based oxide glasses having composition xBi(2)O(3).(0.30 -
      x)PbO.0.70B(2)O(3) have been prepared (0.00 < or = x < or = 0.15, mol%)
      containing 2.0mol% of V(2)O(5) by normal melt-quenching technique. Electron
      paramagnetic resonance (EPR), optical spectra and dc conductivity of these
      glasses have been studied. Spin Hamiltonian parameters (SHP) of VO(2+) ions,
      dipolar hyperfine parameter, P and Fermi contact interaction parameter, K,
      molecular orbital coefficients (alpha(2) and gamma(2)) and optical band gap have
      been calculated. It is observed that in these glasses, the tetragonal nature of
      V(4+)O(6) complex increases with Bi(2)O(3) content. Increase in Bi(2)O(3):PbO
      ratio results in the contraction of 3d(xy) orbit of the unpaired electron in the
      vanadium ion, and the SHP are dependent on the theoretical optical basicity,
      Lambda(th). In present glasses, the conductivity (activation energy) first
      decreases (increases) with increase in mol% of Bi(2)O(3) content upto x = 0.08
      and then shows a maxima (minima) at x = 0.10 and then starts decreasing
      (increasing) upto x < or = 0.15 with mol% of Bi(2)O(3) content.

PMID- 15741121
TI  - A further insight into the mechanism of Ag+ biosorption by Lactobacillus sp.
      strain A09.
AB  - The mechanism of Ag(+) biosorption by resting cell of Lactobacillus sp. strain
      A09 has been further investigated at the molecular level using spectroscopic
      techniques. The values of estimated equilibrium constants, rate constants, half
      life periods and apparent enthalpies of the binding reaction were calculated via
      the determination of Ag(+) adsorbed by the biomass using atomic absorption
      spectrophotometry (AAS). The reductive ratio of the Ag(+) to Ag(0) by the A09
      biomass was examined by X-ray photoelectron spectroscopy (XPS). Analysis for
      sulfur and nitrogen atomic contents in dry powder of the biomass with EA-1110
      elemental analysis (EA) showed that amino acid residues retaining the reductive
      property of Ag(+) to Ag(0) are very small quantity, whereas glucose content in
      the hydrolysates of the biomass analyzed by ultraviolet-visible spectrophotometry
      (UV-vis) indicated that the amount of reducing sugars in the biomass is much
      larger than 2.71%. The fourier transform infrared (FTIR) spectrophotometry on
      blank and silver-loaded biomass demonstrated that the chemical functional group
      such as the free aldehyde group of the hemiacetalic hydroxyl group from reducing
      sugars, i.e. the hydrolysates of the polysaccharides from the cell wall plays a
      leading role in serving as the electron donor for reducing the Ag(+) to Ag(0).
      This result was further supported by characterizations on the interaction of the
      Ag(+) with glucose using X-ray powder diffractometry (XRD) and FTIR spectroscopy.

PMID- 15741122
TI  - Fluorescence determination of DNA with 1-pyrenebutyric acid nanoparticles coated
      with beta-cyclodextrin as a fluorescence probe.
AB  - A novel ultrasonication method has been successfully developed for the
      preparation of 1-pyrenebutyric acid (PBAC)/beta-cyclodextrin(beta-CD) complex
      nanoparticles. The as-prepared nanoparticles are characterized by transmission
      electron microscopy (TEM), fluorescence excitation and emission spectroscopy.
      Complex nanoparticles prepared with ultrasonication are smaller and better
      dispersed than single PBAC nanoparticles. At pH 3.0, the relative fluorescence
      intensity of complex nanoparticles of PBAC/beta-CD can be quenched by the
      concentration of DNA. Based on this, a novel fluorimetric method has been
      developed for rapid determination of DNA. In comparison with single organic
      fluorophores, these nanoparticle probes are better water-solubility, more stable
      and do not suffer from blinking. Under optimum conditions, the calibration graphs
      are linear over the range 0.2-15 microg mL(-1) for calf thymus DNA (ct-DNA) and
      0.3-12 microg mL(-1) for fish sperm DNA (fs-DNA). The corresponding detection
      limit is 0.01 microg mL(-1) for ct-DNA and 0.02 microg mL(-1) for fs-DNA. The
      relative standard deviation of seven replicate measurements is 1.2% for 2.0
      microg mL(-1) ct-DNA and 1.4% for 2.0 microg mL(-1) fs-DNA, respectively. The
      method is simple and sensitive. The recovery and relative standard deviation are
      very satisfactory. A mechanism proposed to explain the process also has been
      studied.

PMID- 15741123
TI  - Structure and stability of arthropodan hemocyanin Limulus polyphemus.
AB  - In the hemolymph of many arthropodan species, respiratory copper proteins of high
      molecular weight, termed hemocyanins (Hcs) are dissolved. In this communication,
      we report on the protein stability of different hemocyanin species (Crustacea and
      Chelicerata) using fluorescence spectroscopy. Five to seven major
      electrophoretically separable protein chains (structural subunits) were purified
      by fast protein liquid chromatography (FPLC) ion exchange chromatography from
      different hemocyanins with very high sequence homology of the active site regions
      binding copper ions (CuA and CuB), and especially the relative sequence positions
      of histidine (His) and tryptophan (Trp) residues of these protein segments are in
      all cases identical. The conformational stabilities of the native dodecameric
      aggregates and their isolated structural subunits towards various denaturants (pH
      and guanidine hydrochloride (Gdn.HCl)) indicate that the quaternary structure is
      stabilized by hydrophilic and polar forces, whereby both, the oxy- and apo-forms
      of the protein are considered. These two classes of Crustacea and Chelicerata Hcs
      have the similar Trp-fluorescence quantum yields, but different values of
      lambda(max) emission (about 325 and 337 nm, respectively). Differences in the
      quantum yields are observed of the oxy- and apo-forms, which must be attributed
      to the fluorescence quenching effect of the two copper ions (CuA and CuB) in the
      active site. The position of emission maximum indicates tryptophan side chains
      are situated in a non-polar environment. Denaturation studies of Hcs by Gdn.HCl
      indicate that the denaturation process consists of two steps: dissociation of the
      native molecule into its structural subunits and denaturation of the subunits at
      concentrations >1.5M Gdn.HCl. Two steps of denaturation are also observed after
      keeping the protein in buffer solutions at different pH values with different pH
      stability for holo-oxy and apo-Hc forms.

PMID- 15741124
TI  - Comparison of energy interaction parameters for the complexation of Pr(III) with
      glutathione reduced (GSH) in absence and presence of Zn(II) in aqueous and
      aquated organic solvents using 4f-4f transition spectra as PROBE.
AB  - The coordination chemistry of glutathione reduced (GSH) is of great importance as
      it acts as excellent model system for the binding of metal ions. The GSH
      complexation with metal ions is involved in the toxicology of different metal
      ions. Its coordination behaviour for soft metal ions and hard metal ions is found
      different because of the structure of GSH and its different potential binding
      sites. In our work we have studied two chemically dissimilar metal ions viz.
      Pr(III), which prefer hard donor site like carboxylic groups and Zn(II) the soft
      metal ion which prefer peptide-NH and sulphydryl groups. The absorption
      difference and comparative absorption spectroscopy involving 4f-4f transitions of
      the heterobimetallic Complexation of GSH with Pr(III) and Zn(II) has been
      explored in aqueous and aquated organic solvents. The variation in the energy
      parameters like Slater-Condon (F(K)), Racah (E(K)) and Lande (xi(4f)),
      Nephelauxetic parameter (beta) and bonding parameter (b(1/2)) are computed to
      explain the nature of complexation.

PMID- 15741125
TI  - A study of quenching effect of sulfur-containing amino acids L-cysteine and L
      methionine on peroxyoxalate chemiluminescence of 7-amino-4
      trifluoromethylcumarin.
AB  - The quenching effect of L-cysteine and L-methionine on strong chemiluminescence
      of bis-(2,4,6-trichlorophenyl)oxalate-H(2)O(2) system in the presence of 7-amino
      4-trifluoromethylcumarin was studied. The chemiluminescence parameters were
      evaluated from computer fitting of the resulting intensity-time plots. Both
      systems resulted in Stern-Volmer plots in the quencher concentration range of 6.5
      x 10(-5) to 5.2 x 10(-4)M with k(Q) values of 1.15 x 10(4) and 1.28 x 10(4)M(-1)
      for L-cysteine and L-methionine, respectively.

PMID- 15741126
TI  - Conformational analysis and comparison between theoretical and experimental
      vibration spectra for isocyanate species on Ag/Al2O3 catalyst.
AB  - Density functional theory (DFT) calculations were performed to study the
      structure and vibrational frequencies of the intermediate for the isocyanate
      (NCO) surface species on Ag/Al(2)O(3) catalyst using the GAUSSIAN 98 suite of
      programs. Thermal decomposition of adsorbed CH(3)NO(2) species leads to the
      formation of two types of NCO species (NCO on Ag and NCO on Al(2)O(3)) above
      298K. In order to investigate the reaction mechanism, we have designed the
      calculated models (a-g) for the NCO intermediate. Through the analysis of the
      vibration mode and the vibration frequency of the calculated models (a-g), we
      conclude that there is an excellent agreement between the calculated vibration
      spectrum of the model (e) containing the -AgNCO group or model (g) containing the
      -AlNCO group and the experimental vibration spectrum.

PMID- 15741127
TI  - The S1 <-- S0 spectrum of jet-cooled p-cymene.
AB  - The spectrum of the first electronic transition of p-cymene cooled in a
      supersonic jet was measured by resonance-enhanced multiphoton ionisation (REMPI)
      in a time-of-flight (TOF) mass spectrometer. The band origin is strong and
      appears at 270.61nm (air value). This spectrum is useful for the detection of p
      cymene in trace analysis.

PMID- 15741128
TI  - EPR parameters and impurity structures for Cr3+ ions in KSc(MoO4)2, RbIn(MoO4)2
      and RbSc(MoO4)2 crystals.
AB  - The calculations of EPR parameters (g factors g||, g(perpendicular) and zero
      field splitting D) related to the impurity structures have been made from the
      high-order perturbation formulas for Cr(3+) ions in trigonal KSc(MoO(4))(2),
      RbIn(MoO(4))(2) and RbSc(MoO(4))(2) crystals. It is found that the MO(6)
      octahedra in these crystals change from the trigonal elongation in the pure
      crystals to the trigonal compression in the impurity centers. The results are
      discussed.

PMID- 15741129
TI  - Inter- and intramolecular excited state proton transfer in 2-hydroxy-9H-carzole-1
      carboxylic acid.
AB  - Absorption, fluorescence and fluorescence excitation spectroscopy and single
      photon counting time dependence spectrofluorimetry have been used to study the
      inter- and intramolecular excited state proton transfer (ESIPT) reactions in 2
      hydroxy-9H-carbazole-1-carboxylic acid (2-HCA). Except in cyclohexane and water
      (pH 5) dual fluorescence is observed in rest of the solvents used. Normal Stokes
      shifted band seems to originate from 2-HCA-1-c and tautomer emission band from
      the tautomer formed by ESIPT in 2-HCA-1-c followed by structural reorganization.
      Both these emission band systems originate from the same ground state species.
      AM1 and CNDO/S-CI calculations have been carried out to establish the identity of
      the species. Different prototropic equilibria have been determined and discussed.

PMID- 15741130
TI  - Study of luminescence properties of novel Er3+ single-doped and Er3+/Yb3+ co
      doped tellurite glasses.
AB  - The novel Er(3+) single-doped and Er(3+)/Yb(3+) co-doped tellurite glasses were
      prepared. The effect of Yb(2)O(3) concentration on absorption spectra, emission
      spectra and upconversion spectra of glasses were measured and investigated. The
      emission intensity, fluorescence full width at half maximum (FWHM) and
      upconversion luminescence of Er(3+) go up with the increasing concentration of
      Yb(3+) ions. The maximum FWHM of (4)I(13/2) --> (4)I(15/2) transition of Er(3+)
      is approximate 77 nm for 1.41 x 10(21)ions/cm(3) concentration of Yb(3+)-doped
      glass. The visible upconversion emissions at about 532, 546 and 659 nm,
      corresponding to the (2)H(11/2) --> (4)I(15/2), (4)S(3/2) --> (4)I(15/2) and
      (4)F(9/2) --> (4)I(15/2) transitions of Er(3+), respectively, were simultaneously
      observed under the excitation at 970 nm. Subsequently, the possible upconversion
      mechanisms and important role of Yb(3+) on the green and red emissions were
      discussed and compared. The results demonstrate that this kind of tellurite glass
      may be a potentially useful material for developing potential amplifiers and
      upconversion optical devices.

PMID- 15741131
TI  - Spectroscopic and thermodynamic study of charge transfer interactions of retinol
      palmitate with [60]- and [70]fullerenes by absorption spectrometric method.
AB  - Retinol palmitate (1), which is commonly called "Vitamin A palmitate", has been
      shown to form charge transfer (CT) complexes with a series of electron acceptors
      including [60]- and [70]fullerenes, and from the trends in CT transition energies
      the vertical ionization potential of 1 has been estimated to be 7.73eV.
      Stoichiometries of the fullerene complexes have been shown to be 1(Vitamin 1):
      1([70]fullerene) and 1(Vitamin 1): 2([60]fullerene). The enthalpies and entropies
      of formation of these two complexes have been determined by estimating the
      formation constants spectrophotometrically at five different temperatures. The
      complexation phenomenon may be utilised to dissolve the fullerenes in the non
      toxic Vitamin A oil and the solution may be used for testing the biological
      activity of the fullerenes in vivo.

PMID- 15741132
TI  - Proton transfer reaction in 4-hydroxy-3-formyl benzoic acid in protic solvents at
      room temperature and 77K and some theoretical aspects.
AB  - Proton transfer processes of 4-hydroxy-3-formyl benzoic acid (HFBA) have been
      studied in a number of different protic solvents by means of absorption, emission
      and nanosecond transient spectroscopy at room temperature and 77K. Intermolecular
      interaction occurs in polar protic solvents only in presence of a base in the
      ground state whereas in the excited state, intermolecular complex formation and
      proton transfer occurs even in pure protic solvents. The dianion is detected in
      water, methanol, ethanol and TFE in presence of base. HFBA shows phosphorescence
      in pure ethanol at 77K. The occurrence of phosphorescence is due to rupture of
      the intramolecular bond and rotation of the formyl group. We have calculated
      quantum yields of fluorescence and also estimated decay rates from nanosecond
      measurements. The energetics of the ground and excited state proton transfer in
      HFBA have been investigated at the AM1 level of approximation. The ground singlet
      is predicted to have a large activation barrier on the proton transfer path,
      while the barrier height is much lower on the corresponding excited singlet
      surface.

PMID- 15741133
TI  - The classification of status epilepticus.

PMID- 15741134
TI  - A semiological classification of status epilepticus.
AB  - The classification of status epilepticus (SE) has been a subject of discussion
      for many years, yet no satisfactory agreement has been reached. Due to their
      complexity, status episodes often defy classification according to the current
      international classification scheme. The semiological seizure classification
      (SSC) has been in use in several epilepsy centers for more than a decade, and has
      proven to be a valid approach to the classification of epileptic seizures. Based
      on the detailed analysis of more than 100 episodes of SE documented with video
      EEG recordings, the authors now present a proposal for a semiological
      classification of status epilepticus (SCSE). The SCSE reflects the assumption
      implied by all modern definitions of SE that "there are as many types of status
      as there are types of seizures" and relies on the same principles as the SSC,
      focusing on the main clinical manifestations and the evolution of the status
      episode. The clinical manifestations of SE are subdivided into semiological
      components and classified along three axes: the type of brain function
      predominantly compromised by the seizure activity, the body part involved, and
      the evolution over time. Each axis contains several subcategories, so that many
      different levels of accuracy are possible. The SCSE, just like the SSC, is meant
      to be part of a comprehensive epilepsy classification which classifies as
      independent variables (epileptogenic zone, ictal semiology, etiology, related
      medical conditions) the main features of the patient's epilepsy, allowing for
      each variable maximum flexibility.

PMID- 15741135
TI  - Symptoms of narcolepsy in children misinterpreted as epilepsy.
AB  - Differentiating an epileptic seizure from some other paroxysmal event is a common
      challenge in clinical practice. Many paroxysmal events mimic epileptic seizures
      and misdiagnosis can have disastrous consequences. Incorrectly identifying an
      event as an epileptic seizure can lead to unnecessary investigations and
      instigation of inappropriate treatment regimes. We report five patients referred
      to regional Paediatric Neuroscience Centres for investigation of events initially
      suspected of being epileptic seizures. All five patients were subsequently
      diagnosed as having narcolepsy. Suspected diagnoses were absence epilepsy (four
      patients), generalized epilepsy with astatic seizures (two patients) and focal
      epileptic seizures (two patients). Diagnostic confusion arose because lack of
      responsiveness due to excessive sleepiness was mistaken for epileptic absences,
      and cataplexy was confused with a variety of seizure types. In each case,
      videotape recording of clinical events aided in making the diagnosis of
      cataplexy. At presentation, all five children had excessive daytime sleepiness
      with cataplexy. Following correct diagnosis and appropriate management, an
      improvement in symptoms was reported in all cases. Narcolepsy/cataplexy should be
      included in the differential diagnoses of paroxysmal disorders, particularly if
      there are associated sleep symptoms or behavioural difficulties. It is important
      to take a sleep history when evaluating any disorder of the central nervous
      system.

PMID- 15741136
TI  - Analysis of the characteristics of epilepsy in 37 patients with the molecular
      diagnosis of Angelman syndrome.
AB  - Angelman syndrome is a genetic disorder caused by defects in the maternally
      inherited imprinted domain located on chromosome 15q11-q13. Most patients with
      Angelman syndrome present with severe mental retardation, characteristic physical
      appearance, behavioral traits, and severe, early-onset epilepsy. We
      retrospectively reviewed the medical histories of 37 patients, all with the
      molecular diagnosis of Angelman syndrome and at least three years of follow-up in
      our neurology department, for further information about their epilepsy: age of
      onset, type of seizures initially and during follow-up, EEG recordings,
      treatments and response. The molecular studies showed 87% deletions de novo, 8%
      uniparental, paternal disomy, and 5% imprinting defects. The median age at
      diagnosis was 6.5 years, with 20% having begun to manifest febrile seizures at an
      average age of 1.9 years. Nearly all (95%) presented with epilepsy, the majority
      under the age of three (76%). The most frequent seizure types were myoclonic,
      atonic, generalized tonic-clonic and atypical absences. At onset, two patients
      exhibited West syndrome. EEG recordings typical of Angelman syndrome were found
      in 68%. Normalization of EEG appeared in 12 patients after nine years. Control of
      epileptic seizures improved after the age of 8.5 years. The most effective
      treatments were valproic acid and clonazepam. We conclude that epilepsy was
      present in nearly all of our cases with Angelman syndrome, and that the EEG can
      be a useful diagnostic tool. On comparing the severity of epilepsy with the type
      of genetic alteration, we did not find any statistically significant
      correlations.

PMID- 15741137
TI  - Generalized tonic-clonic status epilepticus in the elderly in China.
AB  - The proportion of elderly people in China is projected to increase rapidly but
      there is limited information on status epilepticus (SE) in this population. We
      evaluated retrospectively the etiology, response to treatment, outcome and
      predictors of mortality in a group of elderly patients with generalized tonic
      clonic SE in Hong Kong, China. Factors for increased mortality were analyzed
      using a logistic regression model. Of the 80 acute admissions for SE from two
      large urban hospitals over a seven-year period, 1996-2002, the two leading causes
      were attributed to cerebral infarct (n=28, 35%) and cerebral haemorrhage (n=14,
      17.5%). The mean age was 74.2 years (range 60-93 years). At six months from the
      onset of seizures, 26 patients (32.5%) had made a good recovery but another 28
      (35%) had died. Results showed that mortality was associated with increasing age
      (OR 1.08, 95% CI 1.01-1.16) and SE due to an acute symptomatic disturbance (OR
      4.90, 95% CI 1.17-13.67). SE is associated with significant morbidity and
      mortality in this age group.

PMID- 15741138
TI  - Leucopenia and thrombocytopenia possibly associated with lamotrigine use in a
      patient.
AB  - Haematological side effects are rather exceptional with lamotrigine. We report
      the case of a 25-year-old woman with epilepsy who developed combined leucopenia
      and thrombocytopenia eight weeks after starting lamotrigine. Within weeks after
      lamotrigine was discontinued, all of the haematopoietic abnormalities had
      disappeared. To our knowledge, this is the first report of combined leucopenia
      and thrombocytopenia associated with lamotrigine treatment suggesting, in our
      patient, a causal reaction.

PMID- 15741139
TI  - Periodic lateralized epileptiform discharges (PLEDs) as the sole electrographic
      correlate of a complex partial seizure.
AB  - We describe a patient in whom the only electrographic manifestation of a complex
      partial seizure recorded by video-EEG telemetry was periodic lateralized
      epileptiform discharges (PLEDs) with a left anterior temporal emphasis. The
      abnormality, which persisted throughout the whole recorded seizure, lends support
      to the claim that PLEDs can be an ictal phenomenon.

PMID- 15741140
TI  - Ictal movement disorders and hypothalamic hamartoma.
AB  - We report the case of a woman presenting with unusual, symptomatic epilepsy
      related to a hypothalamic hamartoma, in the absence of mental retardation or
      precocious puberty. The seizures manifested themselves clinically as
      characteristic, paroxysmal movement disorders, such as choreic/ballistic
      movement. This type of phenomenon is rarely of epileptic origin: we thus suggest
      that the movement disorder observed here could be due to functional
      disorganization of the basal ganglia network by the epileptic discharge, causing
      loss of the inhibition of thalamic activity and thus allowing the occurrence of
      abnormal movements.

PMID- 15741141
TI  - Startle-induced seizures associated with infantile hemiplegia: implication of the
      supplementary motor area.
AB  - This case illustrates an uncommon form of symptomatic startle-induced epilepsy
      associated with infantile hemiplegia. Seizure semiology, neuroimaging and
      neurophysiological findings support involvement of the supplementary motor area
      in the generation of this seizure type. We present the case of an 11-year-old
      girl with an uncommon form of startle-induced seizures, illustrated on video-EEG,
      against the background of left infantile hemiplegia associated with extensive
      right hemispheric porencephaly but preserved cognitive functioning. The epileptic
      focus appears to be in the dorsolateral frontal lobe, with seizure semiology
      involving the supplementary motor cortex.

PMID- 15741142
TI  - Wall-eyed bilateral internuclear ophtalmoplegia presenting as monocular
      alternating nystagmus: a non-epileptic phenomenon in a case of diffuse axonal
      injury.
AB  - A 15-year-old male in a persistent vegetative state due to diffuse axonal injury
      presented with seizures and spontaneous alternating monocular nystagmus. The
      cranial MRI revealed diffuse axonal injury involving supratentorial and
      infratentorial structures, and the splenium of the corpus callosum. The monocular
      alternating nystagmus was thought to be independent of seizures and occurred as a
      result of diffuse axonal injury affecting the medial longitudinal fasciculus
      bilaterally.

PMID- 15741143
TI  - Neurocutaneous melanosis and epilepsy surgery.

PMID- 15741144
TI  - Gaze-dependent deviation in pointing induced by transcranial magnetic stimulation
      over the human posterior parietal cortex.
AB  - Signals arising from the saccadic system influence the planning and generation of
      pointing movements, and the posterior parietal cortex (PPC) appears to play a
      vital role in that interaction. The authors demonstrate in the present study that
      during visual fixation, eye-position signals can dominate pointing responses when
      the activity in the PPC contralateral to the moving limb is disrupted with
      transcranial magnetic stimulation (TMS). In particular, when presented with
      targets in peripheral vision, participants (N=5) exposed to TMS over the PPC
      failed to show the normal pattern of responses in which pointing movements end up
      farther away from the goal target. Instead, they tended to point more toward the
      current point of visual fixation. Those results suggest that the PPC is involved
      in integrating eye-position and visual information to affect reaching in the
      contralateral arm.

PMID- 15741145
TI  - Soil respiration in a mixed temperate forest and its contribution to total
      ecosystem respiration.
AB  - Soil respiration (SR) was measured with an infrared gas analyzer in nine plots
      representative of the heterogeneous vegetation in a mixed coniferous-deciduous
      forest in the Belgian Campine region. Selected plots included the two most
      representative overstory species (Pinus sylvestris L. and Quercus robur L.) in
      combination with the most representative understory species of the forest. A
      model that includes temperature and water as the main controlling variables was
      fitted to the data. We found large spatial variability in SR among plots, with
      typically lower fluxes under the coniferous overstory than under the deciduous
      overstory (means of 4.8 +/- 0.4 and 8.8 +/- 0.5 Mg C ha(-1) year(-1),
      respectively). Total annual soil carbon (C) emissions were estimated by weighting
      fluxes from different types of vegetation according to their relative
      contribution to the footprint area of the eddy covariance flux measurement. The
      relative contribution of the two main tree species to the footprint-weighted
      total SR varied among seasons with the more abundant coniferous overstory
      contributing the most to total SR during most of the year. Nonetheless, during
      summer, the contribution of deciduous plots to total SR was disproportionally
      high because of the more pronounced seasonality of belowground metabolic
      activity. Net ecosystem carbon dioxide exchange was measured by eddy covariance,
      and we estimated total ecosystem respiration (TER) with footprint-constrained
      nighttime fluxes. Mean total annual SR and TER were 6.1 +/- 0.11 and 9.1 +/- 1.15
      Mg C ha(-1) year(-1), respectively. The 95% confidence interval of the ratio of
      annual SR:TER ranged from 0.58 to 0.76, with a mean of 0.67. The contribution of
      SR to TER tended to vary seasonally, with minimum contributions during summer
      (less than 50% of TER) and maximum contributions during winter (about 94% of
      TER).

PMID- 15741146
TI  - Vertical, horizontal and azimuthal variations in leaf photosynthetic
      characteristics within a Fagus crenata crown in relation to light acclimation.
AB  - An understanding of spatial variations in gas exchange parameters in relation to
      the light environment is crucial for modeling canopy photosynthesis. We measured
      vertical, horizontal and azimuthal (north and south) variations in photosynthetic
      capacity (i.e., the maximum rate of carboxylation: Vcmax), nitrogen content (N),
      leaf mass per area (LMA) and chlorophyll content (Chl) in relation to relative
      photosynthetic photon flux (rPPF) within a Fagus crenata Blume crown. The
      horizontal gradient of rPPF was similar in magnitude to the vertical gradient of
      rPPF from the upper to the lower crown. The rPPF in the north quadrant of the
      crown was slightly lower than in the south quadrant. Nitrogen content per area
      (Narea), LMA and Vcmax were strictly proportional to rPPF, irrespective of the
      vertical direction, horizontal direction and crown azimuth, whereas nitrogen
      content per dry mass, Chl per area and photosynthetic capacity per dry mass (Vm)
      were fairly constant. Statistical analyses separating vertical trends from
      horizontal and azimuthal trends indicated that, although horizontal and vertical
      light acclimation of leaf properties were similar, there were two significant
      azimuthal variations: (1) Vcmax was lower in north-facing leaves than in south
      facing leaves for a given Narea, indicating low photosynthetic nitrogen-use
      efficiency (PNUE) of north-facing leaves; and (2) Vcmax was lower in north-facing
      leaves than in south-facing leaves for a given LMA, indicating low Vm of the
      north-facing leaves. With respect to the low PNUE of the north-facing leaves,
      there were no significant azimuthal variations in leaf CO2 conductance from the
      stomata to the carboxylation site. Biochemical analysis indicated that azimuthal
      variations in nitrogen allocation to ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) and in nitrogen allocation between carboxylation
      (Rubisco and other Calvin cycle enzymes) and light harvesting machinery (Chl
      pigment-protein complexes) were not the main contributor to the difference in
      PNUE between north- and south-facing leaves. Lower specific activity of Rubisco
      may be responsible for the low PNUE of the north-facing leaves. Anatomical
      analysis indicated that not only high leaf density, which is compatible with a
      greater fraction of non-photosynthetic tissue, but also thick photosynthetic
      tissue contributed to the low Vm in the north-facing leaves. These azimuthal
      variations may need to be considered when modeling canopy photosynthesis based on
      the Narea-Vcmax or LMA-Vcmax relationship.

PMID- 15741147
TI  - Influences of environmental factors on the radial profile of sap flux density in
      Fagus crenata growing at different elevations in the Naeba Mountains, Japan.
AB  - Sap flux density was measured continuously during the 1999 and 2000 growing
      seasons by the heat dissipation method in natural Fagus crenata Blume (Japanese
      beech) forests growing between 550 and 1600 m on the northern slope of the Kagura
      Peak of the Naeba Mountains, Japan. Sap flux density decreased radially toward
      the inner xylem and the decrease was best expressed in relation to the number of
      annual rings from the cambium, or in relation to the relative depth between the
      cambium and the trunk center, rather than as a function of absolute depth. The
      relative influences of radiation, vapor pressure deficit and soil water on sap
      flux density during the growing season were similar for the outer and inner
      xylem, and at all sites. Measurements of soil water content and water potential
      at a depth of 0.25 m demonstrated that sap flux density responded similarly and
      sensitively to water potential changes in this soil layer, despite large
      differences in rooting depth at different elevations, localizing one important
      control point in the functioning of this forest ecosystem. Identification of the
      relative influences of radiation, vapor pressure deficit and drying of the upper
      soil layer on sap flux density provides a framework for in-depth analysis of the
      control of transpiration in Japanese beech forests. In addition, the finding that
      the same general controls are operating on sap flux density despite climate
      gradients and large differences in overall forest stand structure will enhance
      understanding of water use by forests along elevation gradients.

PMID- 15741148
TI  - Leaf photosynthetic characteristics of silver birch during three years of
      exposure to elevated concentrations of CO2 and O3 in the field.
AB  - Effects of elevated concentrations of carbon dioxide ([CO2]) and ozone ([O3]) on
      photosynthesis and related biochemistry of two European silver birch (Betula
      pendula Roth) clones were studied under field conditions during 1999-2001. Seven
      year-old trees of Clones 4 and 80 were exposed for 3 years to the following
      treatments in an open-top chamber experiment: outside control (OC), chamber
      control (CC), 2x ambient [CO2] (EC), 2x ambient [O3] (EO) and 2x ambient [CO2] +
      2x ambient [O3] (EC+EO). During the experiment, gas exchange, chlorophyll
      fluorescence, amount and activity of Rubisco, concentrations of chlorophyll,
      soluble protein, soluble sugars, starch, nitrogen (N) and carbon:nitrogen (C:N)
      ratio were determined in short- and long-shoot leaves. Elevated [CO2] increased
      photosynthetic rate by around 30% when measurements were made at the growth
      [CO2]. When measured at ambient [CO2], photosynthesis was around 15% lower in EC
      trees than in CC trees. This was related to a approximately 10% decrease in total
      leaf N, to 26 and 20% decreases in the amount and activity of Rubisco,
      respectively, and to a 49% increase in starch concentration in elevated [CO2].
      Elevated [O3] had no significant effect on gas exchange parameters and its effect
      on biochemistry was small in both clones. However, elevated [O3] decreased the
      proportion of Rubisco in total soluble proteins and the apparent quantum yield of
      photosystem II (PSII) photochemistry in light and increased non-photochemical
      quenching in 2000. The interactive effect of CO2 and O3 was variable. Elevated
      [O3] decreased chlorophyll concentration only in EO trees, and the EC+EO
      treatment decreased the total activity of Rubisco and increased the C:N ratio
      more than the EO treatment alone. The small effect of elevated [O3] on
      photosynthesis indicates that these young silver birches were fairly tolerant to
      annual [O3] exposures that were 2-3 times higher than the AOT40 value of 10
      ppm.h. set as a critical dose for forest trees.

PMID- 15741149
TI  - Ontogenetic transition of leaf physiology and anatomy from seedlings to mature
      trees of a rain forest pioneer tree, Macaranga gigantea.
AB  - In a field study, we compared anatomy and diurnal gas exchange and chlorophyll
      fluorescence in sunlit mature leaves of Macaranga gigantea (Reichb. f. and Zoll.)
      Muell. seedlings, saplings, an adult tree and suckers originating from stumps. We
      tested the hypothesis that the pattern of resource use shifts across various life
      stages with ontogenetic changes in leaf anatomy and physiology. Among leaves of
      different developmental stages, seedling leaves were the smallest and thinnest,
      whereas adult tree leaves were the largest and thickest, and the air space within
      the lamina was largest in seedling leaves and smallest in adult tree leaves.
      Photosynthetic nitrogen-use efficiency (PNUE) was higher in seedling and sapling
      leaves than in adult tree leaves. Mean PNUE in seedling leaves was 1.6 times that
      in adult tree leaves. Nevertheless, among the developmental stages, net
      photosynthetic rate (Pn) per unit leaf area was lowest in seedling leaves because
      they have the lowest nitrogen (N) content per unit leaf area. In situ water vapor
      stomatal conductance (g(s) at a given leaf-to-air vapor pressure deficit was
      highest in sapling leaves, suggesting that they have a high hydraulic efficiency
      per unit leaf area. Among developmental stages, intrinsic water-use efficiency
      (Pn/g(s)) and photochemical capacity of photosystem II were lowest in seedling
      leaves. Sapling leaves had the highest N concentration and Pn per unit dry mass
      and the highest g(s), indicating that the gradual transition from the seedling
      stage to the sapling stage is accompanied by an accumulation of N in plant bodies
      and the development of hydraulic systems to counteract unfavorable environmental
      stresses. The properties of adult tree leaves (low PNUE, high carbon:N ratio,
      small and dense cells and thick lamina) indicate that, during the transition from
      the sapling stage to the adult tree stage, the priority of resource use in leaves
      gradually shifts from enhancement of photosynthetic performance to defense
      against herbivory and mechanical damage. Leaf morphology and physiology were
      coordinated with the differences in resource use at each life stage.

PMID- 15741150
TI  - Growth efficiency increases as relative growth rate increases in shoots and roots
      of Eucalyptus globulus deprived of nitrogen or treated with salt.
AB  - We used calorimetry to test whether there is a single general relationship
      between growth and respiration in shoots and roots of Eucalyptus globulus Labill.
      seedlings when stressed, irrespective of the type or severity of stress. We found
      that nitrogen (N) deprivation and salt treatment had no effect on the
      relationship between growth and respiration and little effect on absolute rates
      of respiration. Carbon-conversion efficiency (epsilonC) ranged from 0.7 to 0.9
      for specific growth rates (R(SG)) greater than 0.3 day(-1). Above an R(SG) of 0.1
      day(-1), epsilonC decreased gradually with decreasing R(SG) and between an R(SG)
      of 0- 0.1 day(-1), epsilonC decreased rapidly. We conclude that the relationship
      between epsilonC and R(SG) is not greatly affected by salt or N-deprivation
      stresses. Relationships between gross productivity and epsilonC may be generally
      applicable, in which case they could improve on the "flat-tax" approach to
      modeling net primary productivity from gross productivity while avoiding the
      complexity of more explicit models of plant respiration. However, the
      relationship between gross productivity and epsilonC was sensitive to temperature
      and the effect of temperature on epsilonC thus requires further investigation.
      Nitrogen deprivation caused large decreases in leaf area and shoot to root ratio,
      and mature leaves of N-deprived plants had lower intrinsic water-use efficiencies
      than leaves of plants well supplied with nutrients. Nitrogen deprivation
      increased apical dominance and most of the reduction in leaf area was the result
      of fewer secondary branches, although leaf size was also reduced. Our results
      suggest that N deprivation reduces productivity primarily by reducing sink size,
      rather than sink activity, and that apical dominance may be an important
      mechanism for maintaining adequate epsilonC in resource-limited conditions.

PMID- 15741151
TI  - Modeling effects of weather and source-sink relationships on mango fruit growth.
AB  - We modeled the effects of weather and source-sink factors on mango fruit growth.
      The peach fruit-growth model "Cashoo" was adapted for mango fruit. The model
      accounts for the main processes of fruit growth, i.e., leaf photosynthesis, fruit
      demand, fruit respiration, and storage and mobilization of leaf and stem
      reserves. Simulations for three successive years and for various leaf-to-fruit
      ratio treatments showed good agreement with observed fruit growth data.
      Simulations of fruit growth under different climatic conditions, especially with
      contrasting temperature and radiation, and for different values of initial fruit
      dry mass and leaf-to-fruit ratio, showed that variations in fruit growth among
      years can be partly explained by climatic variations through their effects on
      leaf photosynthesis, fruit demand and fruit growth rate. However, climatic
      changes contribute substantially less to observed variability in fruit growth
      than to initial fruit dry mass and leaf-to-fruit ratio.

PMID- 15741152
TI  - Seasonal changes in photosynthesis and photoprotection in a Quercus ilex subsp.
      ballota woodland located in its upper altitudinal extreme in the Iberian
      Peninsula.
AB  - Quercus ilex L. subsp. ballota (Desf.) Samp., a Mediterranean evergreen species
      growing in a continental Mediterranean climate, did not experience water stress
      and showed greater sensitivity to winter stress than to summer stress over a 12
      month period. Net CO2 assimilation rates and photosystem II (PSII) efficiency
      decreased markedly during the cold months and recovered completely in spring.
      Lutein, neoxanthin and beta-carotene to chlorophyll (Chl) molar ratios all showed
      the same trend throughout the year, increasing from September to March. This
      increase was a result of increases in carotenoid concentrations, because Chl
      concentration per unit leaf area remained stable, and was higher at the end than
      at the beginning of the first growing season. Lutein-epoxide was a minor
      component of the total lutein pool. Thermal energy dissipation and non
      photochemical quenching (NPQ) were associated with the de-epoxidated forms of the
      xanthophyll cycle pigments in the warm months. Photosynthetic rates decreased
      slightly at midday in summer. These changes were accompanied by decreases in
      maximum potential PSII efficiency (which recovered during the night), actual and
      intrinsic PSII efficiencies, photochemical quenching and increases in NPQ.
      Overall, our data indicate down-regulation of photosynthesis during the summer.
      The diurnal de-epoxidation of violaxanthin to antheraxanthin and zeaxanthin
      occurred throughout the year, except in January. Antioxidant enzymatic activity
      increased in the winter months, especially during the coldest months,
      highlighting its key role in photoprotection against photo-oxidation. Structural
      and functional modifications protected PSII from permanent damage and allowed 1
      year-old leaves to photosynthesize at high rates when temperatures increased in
      spring.

PMID- 15741153
TI  - Effects of soil temperature and elevated atmospheric CO2 concentration on gas
      exchange, in vivo carboxylation and chlorophyll fluorescence in jack pine and
      white birch seedlings.
AB  - One-year-old jack pine (Pinus banksiana Lamb.) and current-year white birch
      (Betula papyrifera Marsh.) seedlings were grown in ambient (360 ppm) or twice
      ambient (720 ppm) atmospheric CO2 concentration ([CO2]) and at three soil
      temperatures (Tsoil = 7, 17 and 27 degrees C initially, increased to 10, 20 and
      30 degrees C two months later, respectively) in a greenhouse for 4 months. In
      situ foliar gas exchange, in vivo carboxylation characteristics and chlorophyll
      fluorescence were measured after 2.5 and 4 months of treatment. Low Tsoil
      suppressed net photosynthetic rate (Pn), stomatal conductance (g(s)) and
      transpiration rate (E) in jack pine in both CO2 treatments and g(s) and E in
      white birch in ambient [CO2], but enhanced instantaneous water-use efficiency
      (IWUE) in both species after 2.5 months of treatment. Treatment effects on g(s)
      and E remained significant throughout the 4-month study. Low Tsoil reduced
      maximal carboxylation rate (Vcmax) and PAR-saturated electron transport rate
      (Jmax) in jack pine in elevated [CO2] after 2.5 months of treatment, but not
      after 4 months of treatment. Low Tsoil increased actual photochemical efficiency
      of photosystem II (PSII) in the light (DeltaF/Fm') in jack pine, but decreased
      DeltaF/Fm' in white birch after 4 months of treatment. In response to low Tsoil,
      photosynthetic linear electron transport to carboxylation (Jc) decreased in jack
      pine after 2.5 months and in white birch after 4 months of treatment. Low Tsoil
      increased the ratio of the photosynthetic linear electron transport to
      oxygenation (Jo) to the total photosynthetic linear electron transport rate
      through PSII (Jo/J(T)) in both species after 2.5 months of treatment, but the
      effects became statistically insignificant in white birch after 4 months of
      treatment. High Tsoil decreased foliar N concentration in white birch. Elevated
      [CO2] increased Pn, IWUE and Jc but decreased Jo/J(T) in both species at both
      measurement times except Jc in white birch after 2.5 months of treatment.
      Elevated [CO2] also decreased g(s) and E in white birch at high Tsoil, Vcmax in
      both species and triose phosphate utilization in white birch at low Tsoil after 4
      months of treatment, and DeltaF/Fm' in white birch after 2.5 months of treatment.
      Elevated [CO2] also increased foliar N concentration in both species. Low Tsoil
      caused no permanent damage to PSII in either species, but jack pine responded and
      acclimated to low Tsoil more quickly than white birch. Photosynthetic down
      regulation and a decrease in photosynthetic electron transport to
      photorespiration occurred in both species in response to elevated [CO2].

PMID- 15741154
TI  - Comparison of cellulose extraction methods for analysis of stable-isotope ratios
      of carbon and oxygen in plant material.
AB  - The Jayme-Wise and diglyme-HCl methods for extracting cellulose from plant
      material for stable-isotope analysis differ considerably in ease of use, with the
      latter requiring significantly less time and specialized equipment. However, the
      diglyme-HCl method leaves a small lignin residue in the crude cellulose that may
      affect stable-isotope values, whereas alpha-cellulose produced by the Jayme-Wise
      method is relatively pure. We examined whether adding a bleaching step to the
      diglyme-HCl method could produce cellulose of comparable purity to alpha
      cellulose by comparing the yield, percent carbon, and carbon (delta13C) and
      oxygen (delta18O) stable isotope ratios of the two celluloses. We tested each
      method on the wood of five species that differ in ease of delignification,
      Eucalyptus maculata Hook., E. botryoides Sm., E. resinifera Sm., Pinus pinaster
      Ait. and Callitris glaucophylla J. Thompson & L.A.S. Johnson, as well as the
      foliage of C. glaucophylla. For hardwoods such as the eucalypts, the diglyme-HCl
      method without bleaching produced cellulose with delta13C and delta18O ratios
      similar to alpha-cellulose. For the softwood, C. glaucophylla, 3 h of bleaching
      with acidified chlorite following treatment with diglyme-HCl produced cellulose
      with delta13C and delta18O ratios similar to alpha-cellulose. Bleached and
      unbleached crude celluloses and alpha-cellulose of P. pinaster were similar in
      delta18O, but not delta13C. Both types of crude cellulose produced from the
      foliage of C. glaucophylla had significantly different isotope ratios from alpha
      cellulose. Overall, the diglyme-HCl method, with or without bleaching, appears to
      be a simple, fast method for extracting alpha-cellulose from hardwoods for stable
      isotope analyses, but its suitability for softwoods and foliage needs to be
      evaluated depending on the species.

PMID- 15741155
TI  - Photosynthesis of the grapevine (Vitis vinifera) inflorescence.
AB  - To further characterize carbohydrate physiology in grapevine flowers, we examined
      inflorescence autotrophy in the 'Gewurztraminer' and 'Pinot noir' cultivars,
      which differ in sensitivity to flower abscission. In both cultivars, positive net
      photosynthesis occurred in inflorescences. The rate of photosynthesis gradually
      decreased throughout flower development and there was no net carbon assimilation
      at fruit set. The rate of photosynthesis was positively correlated with
      chlorophyll concentration but not to stomatal conductance. Throughout flower
      development, the internal CO2 concentration increased in inflorescence tissues,
      suggesting that assimilates are also formed through refixation of respiratory CO2
      by the phosphoenolpyruvate carboxylase (PEPC) pathway. Significant differences
      between the two cultivars were recorded during meiosis, when photosynthesis was
      higher in 'Gewurztraminer'. We conclude that the inflorescence of grapevine
      contributes to its own carbon nutrition by photosynthesizing throughout flower
      development. Moreover, the differential patterns of photosynthesis in the
      inflorescences of 'Gewurztraminer' and 'Pinot noir' might account for their
      differing fertilization rates and sensitivity to flower abscission.

PMID- 15741156
TI  - Leaf longevity of western red cedar (Thuja plicata) increases with depth in the
      canopy.
AB  - Leaf longevity determines the annual cost of replacing foliage biomass and
      influences water and nutrient budgets. Longevity is readily estimated in most
      evergreen species by annual bud scars along the shoot. However, some species with
      indeterminate growth do not show these annual markers, making estimation of
      longevity difficult. One of these species is the widespread and economically
      valuable western red cedar (Thuja plicata J. Donn ex D. Don), for which no
      dependable estimates of leaf longevity exist. In this study, we estimated leaf
      longevity for western red cedar by counting growth rings in shoots at the point
      of leaf abscission. Estimates were obtained on 26 dominant or codominant trees
      growing in natural stands in a montane forest in northern Idaho, USA. Leaf
      longevity averaged 8.9 (SE = 0.2) years, but it strongly increased with depth in
      the canopy (0.3 year m(-1); mean crown depth was 15 m), increasing from a mean of
      6.8 years in the upper third of the canopy to 10.6 years in the lower third. The
      increase in longevity with depth in the crown is consistent with many reports
      showing that longevity increases in resource-limiting environments. Longevity did
      not vary significantly with altitude or solar insolation in these montane
      forests. Among stand-level variables, longevity was correlated only with leaf
      area index: it increased slightly in stands with high leaf area indices. This
      approach to longevity estimation may be useful for any species that produces
      annual rings but no obvious bud scars, including many Cupressaceae species.

PMID- 15741157
TI  - Genetically engineered production of 1-desmethylcobyrinic acid, 1
      desmethylcobyrinic acid a,c-diamide, and cobyrinic acid a,c-diamide in
      Escherichia coli implies a role for CbiD in C-1 methylation in the anaerobic
      pathway to cobalamin.
AB  - Co-expression of the cobA gene from Propionibacterium freudenreichii and the
      cbiA, -C, -D, -E, -T, -F, -G, -H, -J, -K, -L, and -P genes from Salmonella
      enterica serovar typhimurium in Escherichia coli resulted in the production of
      cobyrinic acid a,c-diamide. A cbiD deletion mutant of this strain produced 1
      desmethylcobyrinic acid a,c-diamide, indicating that CbiD is involved in C-1
      methylation in the anaerobic pathway to cobalamin. Strains that did not have the
      cbiP gene also produced 1-desmethylcobyrinic acid a,c-diamide, and strains that
      had neither cbiP nor cbiA synthesized 1-desmethylcobyrinic acid even in the
      presence of cbiD, suggesting that CbiA and CbiP are necessary for CbiD activity.

PMID- 15741158
TI  - A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and
      chymase: molecular mechanisms and anti-inflammatory activity in vivo.
AB  - Certain leukocytes release serine proteases that sustain inflammatory processes
      and cause disease conditions, such as asthma and chronic obstructive pulmonary
      disease. We identified beta-ketophosphonate 1 (JNJ-10311795; RWJ-355871) as a
      novel, potent dual inhibitor of neutrophil cathepsin G (K(i) = 38 nm) and mast
      cell chymase (K(i) = 2.3 nm). The x-ray crystal structures of 1 complexed with
      human cathepsin G (1.85 A) and human chymase (1.90 A) reveal the molecular basis
      of the dual inhibition. Ligand 1 occupies the S(1) and S(2) subsites of cathepsin
      G and chymase similarly, with the 2-naphthyl in S(1), the 1-naphthyl in S(2), and
      the phosphonate group in a complex network of hydrogen bonds. Surprisingly,
      however, the carboxamido-N-(naphthalene-2-carboxyl)piperidine group is found to
      bind in two distinct conformations. In cathepsin G, this group occupies the
      hydrophobic S(3)/S(4) subsites, whereas in chymase, it does not; rather, it folds
      onto the 1-naphthyl group of the inhibitor itself. Compound 1 exhibited
      noteworthy anti-inflammatory activity in rats for glycogen-induced peritonitis
      and lipopolysaccharide-induced airway inflammation. In addition to a marked
      reduction in neutrophil influx, 1 reversed increases in inflammatory mediators
      interleukin-1alpha, interleukin-1beta, tissue necrosis factor-alpha, and monocyte
      chemotactic protein-1 in the glycogen model and reversed increases in airway
      nitric oxide levels in the lipopolysaccharide model. These findings demonstrate
      that it is possible to inhibit both cathepsin G and chymase with a single
      molecule and suggest an exciting opportunity in the treatment of asthma and
      chronic obstructive pulmonary disease.

PMID- 15741159
TI  - Role of regulatory F-domain in hepatocyte nuclear factor-4alpha ligand
      specificity.
AB  - The F-domain of rat HNF-4alpha1 has a crucial impact on the ligand binding
      affinity, ligand specificity and secondary structure of HNF-4alpha. (i)
      Fluorescent binding assays indicate that wild-type, full-length HNF-4alpha (amino
      acids 1-455) has high affinity (Kd=0.06-12 nm) for long chain fatty acyl-CoAs
      (LCFA-CoA) and low affinity (Kd=58-296 nm) for unesterified long chain fatty
      acids (LCFAs). LCFA-CoA binding was due to close molecular interaction as shown
      by fluorescence resonance energy transfer (FRET) from full-length HNF-4alpha
      tryptophan (FRET donor) to bound cis-parinaroyl-CoA (FRET acceptor), which
      yielded an intermolecular distance of 33 A, although no FRET to cis-parinaric
      acid was detected. (ii) Deleting the N-terminal A-D-domains, comprising the AF1
      and DNA binding functions, only slightly affected affinities for LCFA-CoAs
      (Kd=0.9-4 nm) and LCFAs (Kd=93-581 nm). (iii) Further deletion of the F-domain
      robustly reduced affinities for LCFA-CoA and reversed ligand specificity (i.e.
      high affinity for LCFAs (Kd=1.5-32 nm) and low affinity for LCFA-CoAs (Kd=54-302
      nm)). No FRET from HNF-4alpha-E (amino acids 132-370) tryptophan (FRET donor) to
      bound cis-parinaroyl-CoA (FRET acceptor) was detected, whereas an intermolecular
      distance of 28 A was calculated from FRET between HNF-4alpha-E and cis-parinaric
      acid. (iv) Circular dichroism showed that LCFA-CoA, but not LCFA, altered the
      secondary structure of HNF-4alpha only when the F-domain was present. (v) cis
      Parinaric acid bound to HNF-4alpha with intact F-domain was readily displaceable
      by S-hexadecyl-CoA, a nonhydrolyzable thioether analogue of LCFA-CoAs. Truncation
      of the F-domain significantly decreased cis-parinaric acid displacement. Hence,
      the C-terminal F-domain of HNF-4alpha regulated ligand affinity, ligand
      specificity, and ligand-induced conformational change of HNF-4alpha. Thus,
      characteristics of F-domain-truncated mutants may not reflect the properties of
      full-length HNF-4alpha.

PMID- 15741160
TI  - The macrophage alphaMbeta2 integrin alphaM lectin domain mediates the
      phagocytosis of chilled platelets.
AB  - alpha(M)beta(2) integrin receptors on myeloid cells mediate the adhesion or
      uptake of diverse ligands. Ligand binding occurs in the alpha(M) chain, which is
      composed of an I domain and a lectin domain. The alpha(M) I domain binds iC3b,
      fibrinogen, intercellular adhesion molecule-1, and other ligands and mediates the
      adhesion of neutrophils to platelet glycoprotein Ibalpha (GPIbalpha).
      alpha(M)beta(2) also recognizes beta-GlcNAc residues on GPIbalpha that are
      clustered on platelets after cooling. The phagocytosis of chilled platelets could
      be reconstituted when Chinese hamster ovary cells were transfected with
      alpha(M)beta(2). Replacement of the I domain or the lectin domain of the alpha(M)
      chain with the corresponding domain from the alpha(X) chain (p150) revealed that
      the activity of the alpha(M)beta(2) integrin toward chilled platelets resides
      within the lectin domain and does not require the I domain. Additional evidences
      for this conclusion are: 1) Sf9 cells expressing solely the alpha(M) lectin
      domain bound chilled platelets, and 2) soluble recombinant alpha(M) lectin domain
      inhibited the phagocytosis of chilled platelets by alpha(M)beta(2)-expressing THP
      1 cells, whereas I domain substrates showed no inhibitory effect. Therefore
      chilled platelets are removed from blood by an interaction between beta-GlcNAc
      residues on clustered GPIbalpha and the lectin domain of alpha(M) chain of the
      alpha(M)beta(2) integrin, distinguishing this interaction from those mediated by
      the alpha(M) I domain.

PMID- 15741161
TI  - Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting
      apoptosis and enhancing resistance to chemotherapy-induced apoptosis. Novel role
      for an old enemy.
AB  - Tumor removal remains the principal treatment modality in the management of solid
      tumors. The process of tumor removal may potentiate the resurgent growth of
      residual neoplastic tissue. Herein, we describe a novel murine model in which
      flank tumor cytoreduction is followed by accelerated local tumor recurrence. This
      model held for primary and recurrent tumors generated using a panel of human and
      murine (LS174T, DU145, SW480, SW640, and 3LL) cell lines and replicated
      accelerated tumor growth following excisional surgery. In investigating this
      further, epithelial cells were purified from LS174T primary and corresponding
      recurrent tumors for comparison. Baseline as well as tumor necrosis factor
      apoptosis-inducing ligand (TRAIL)-induced apoptosis were significantly reduced in
      recurrent tumor epithelia. Primary and recurrent tumor gene expression profiles
      were then compared. This identified an increase and reduction in the expression
      of p110gamma and p85alpha class Ia phosphoinositide 3-kinase (PI3K) subunits in
      recurrent tumor epithelia. These changes were further confirmed at the protein
      level. The targeting of PI3K ex vivo, using LY294002, restored sensitivity to
      TRAIL in recurrent tumor epithelia. In vivo, adjuvant LY294002 prolonged survival
      and significantly attenuated recurrent tumor growth by greatly enhancing
      apoptosis levels. Hence, PI3K plays a role in generating the antiapoptotic and
      chemoresistant phenotype associated with accelerated local tumor recurrence.

PMID- 15741162
TI  - A direct signaling role for phosphatidylinositol 4,5-bisphosphate (PIP2) in the
      visual excitation process of microvillar receptors.
AB  - In microvillar photoreceptors the pivotal role of phospholipase C in light
      transduction is undisputed, but previous attempts to account for the
      photoresponse solely in terms of downstream products of phosphatidylinositol 4,5
      bisphosphate (PIP2) hydrolysis have proved wanting. In other systems PIP2 has
      been shown to possess signaling functions of its own, rather than simply serving
      as a precursor molecule. Because illumination of microvillar photoreceptors cells
      leads to PIP2 break-down, a potential role for this phospholipid in
      phototransduction would be to help maintain some element(s) of the transduction
      cascade in the inactive state. We tested the effect of intracellular dialysis of
      PIP2 on voltage-clamped molluscan photoreceptors and found a marked reduction in
      the amplitude of the photocurrent; by contrast, depolarization-activated calcium
      and potassium currents were unaffected, thus supporting the notion of a specific
      effect on light signaling. In the dark, PIP2 caused a gradual outward shift of
      the holding current; this change was due to a decrease in membrane conductance
      and may reflect the suppression of basal openings of the light-sensitive
      conductance. The consequences of depleting PIP2 were examined in patches of light
      sensitive microvillar membrane screened for the exclusive presence of light
      activated ion channels. After excision, superfusion with anti-PIP2 antibodies
      induced the appearance of single-channel currents. Replenishment of PIP2 by
      exogenous application reverted the effect. These data support the notion that
      PIP2, in addition to being the source of inositol trisphosphate and
      diacylglycerol, two messengers of visual excitation, may also participate in a
      direct fashion in the control of the light-sensitive conductance.

PMID- 15741163
TI  - Cdk2-dependent phosphorylation of homeobox transcription factor CDX2 regulates
      its nuclear translocation and proteasome-mediated degradation in human intestinal
      epithelial cells.
AB  - By having demonstrated previously that p27(Kip1), a potent inhibitor of G(1)
      cyclin-cyclin-dependent kinases complexes, increases markedly during intestinal
      epithelial cell differentiation, we examined the effect of p27(Kip1) on the
      activity of the transcription factor CDX2. The present results revealed the
      following. 1) p27(Kip1) interacts with the CDX2 transcription factor. 2) In
      contrast to CDX2 mRNA levels, CDX2 protein expression levels significantly
      increased as soon as Caco-2/15 cells reached confluence, slowed their
      proliferation, and began their differentiation. The mechanism of CDX2 regulation
      is primarily related to protein stability, because inhibition of proteasome
      activity increased CDX2 levels. The half-life of CDX2 protein was significantly
      enhanced in differentiated versus undifferentiated proliferative intestinal
      epithelial cells. 3) Cdk2 interacted with CDX2 and phosphorylated CDX2, as
      determined by pull-down glutathione S-transferase and immunoprecipitation
      experiments with proliferating undifferentiated Caco-2/15 cell extracts. 4)
      Treatment of Caco-2/15 cells with MG132 (a proteasome inhibitor) and (R)
      roscovitine (a specific Cdk2 inhibitor) induced an increase in CDX2 protein
      levels. 5) Conversely, ectopic expression of Cdk2 resulted in decreased
      expression of CDX2 protein. 6) Of note, treatment of proliferative Caco-2/15
      cells with (R)-roscovitine or leptomycin (an inhibitor of nuclear export through
      CRM1) led to an accumulation of CDX2 into the nucleus. These data suggest that
      CDX2 undergoes CRM1-dependent nuclear export and cytoplasmic degradation in cells
      in which Cdk2 is activated, such as in proliferative intestinal epithelial cells.
      The targeted degradation of CDX2 following its phosphorylation by Cdk2 identifies
      a new mechanism through which CDX2 activity can be regulated in coordination with
      the cell cycle machinery.

PMID- 15741164
TI  - Upstream stimulatory factors (USF-1/USF-2) regulate human cGMP-dependent protein
      kinase I gene expression in vascular smooth muscle cells.
AB  - Cyclic GMP-dependent protein kinase I plays a pivotal role in regulating smooth
      muscle cell relaxation, growth, and differentiation. Expression of the enzyme
      varies greatly in smooth muscle and in other tissues and cell types, yet little
      is known regarding the mechanisms regulating cGMP-dependent protein kinase gene
      expression. The present work was undertaken to characterize the mechanisms
      controlling kinase gene expression in vascular smooth muscle cells. A 2-kb human
      cGMP-dependent protein kinase I 5'-noncoding promoter sequence was characterized
      by serial deletion, and functional studies demonstrated that a 591-bp 5'-promoter
      construct possessed the highest activity compared with all other constructs
      generated from the larger promoter. Analysis of the sequence between -472 and 
      591 bp from the transcriptional start site revealed the existence of two E-like
      boxes known to bind upstream stimulatory factors. Electrophoretic mobility shift
      assays and functional studies using luciferase reporter gene assays identified
      upstream stimulatory factors as the transcription factors bound to the E-boxes in
      the 591-bp promoter. Site-directed mutagenesis of the E-boxes abolished the
      binding of upstream stimulatory factor proteins and decreased the activity of the
      cGMP-dependent protein kinase I 591-bp promoter, thus confirming the involvement
      of these transcription factors in mediating gene expression. Cotransfection
      experiments demonstrated that overexpression of upstream stimulatory factors 1
      and 2 increased cGMP-dependent protein kinase I promoter activity. Collectively,
      these data suggest that the human proximal cGMP-dependent protein kinase I
      promoter is regulated by tandem E-boxes that bind upstream stimulatory factors.

PMID- 15741165
TI  - p400 is required for E1A to promote apoptosis.
AB  - The adenovirus E1A oncoprotein promotes proliferation and transformation by
      binding cellular proteins, including members of the retinoblastoma protein
      family, the p300/CREB-binding protein transcriptional coactivators, and the p400
      TRRAP chromatin-remodeling complex. E1A also promotes apoptosis, in part, by
      engaging the ARF-p53 tumor suppressor pathway. We show that E1A induces ARF and
      p53 and promotes apoptosis in normal fibroblasts by physically associating with
      the retinoblastoma protein and a p400-TRRAP complex and that its interaction with
      p300 is largely dispensable for these effects. We further show that E1A increases
      p400 expression and, conversely, that suppression of p400 using stable RNA
      interference reduces the levels of ARF, p53, and apoptosis in E1A-expressing
      cells. Therefore, whereas E1A inactivates the retinoblastoma protein, it requires
      p400 to efficiently promote cell death. These results identify p400 as a
      regulator of the ARF-p53 pathway and a component of the cellular machinery that
      couples proliferation to cell death.

PMID- 15741166
TI  - Small interference RNA-mediated gene silencing of human biliverdin reductase, but
      not that of heme oxygenase-1, attenuates arsenite-mediated induction of the
      oxygenase and increases apoptosis in 293A kidney cells.
AB  - BVR reduces biliverdin, the HO-1 and HO-2 product, to bilirubin. Human biliverdin
      (BVR) is a serine/threonine kinase activated by free radicals. It is a leucine
      zipper (bZip) DNA-binding protein and a regulatory factor for 8/7-bp AP-1
      regulated genes, including HO-1 and ATF-2/CREB. Presently, small interference
      (si) RNA constructs were used to investigate the role of human BVR in sodium
      arsenite (As)-mediated induction of HO-1 and in cytoprotection against apoptosis.
      Activation of BVR involved increased serine/threonine phosphorylation but not its
      protein or transcript levels. The peak activity at 1 h (4-5-fold) after treatment
      of 293A cells with 5 mum As preceded induction of HO-1 expression by 3 h. The
      following suggests BVR involvement in regulating oxidative stress response of HO
      1: siBVR attenuated As-mediated increase in HO-1 expression; siBVR, but not siHO
      1, inhibited As-dependent increased c-jun promoter activity; treatment of cells
      with As increased AP-1 binding of nuclear proteins; BVR was identified in the DNA
      protein complex; and AP-1 binding of the in vitro translated BVR was
      phosphorylation-dependent and was attenuated by biliverdin. Most unexpectedly,
      cells transfected with siBVR, but not siHO-1, displayed a 4-fold increase in
      apoptotic cells when treated with 10 mum As as detected by flow cytometry. The
      presence of BVR small interference RNA augmented the effect of As on levels of
      cytochrome c, TRAIL, and DR-5 mRNA and cleavage of poly(ADP-ribose) polymerase.
      The findings describe the function of BVR in HO-1 oxidative response and,
      demonstrate, for the first time, not only that BVR advances the role of HO-1 in
      cytoprotection but also affords cytoprotection independent of heme degradation.

PMID- 15741168
TI  - Exocytic trafficking is required for nicotine-induced up-regulation of alpha 4
      beta 2 nicotinic acetylcholine receptors.
AB  - The primary target for nicotine in the brain is the neuronal nicotinic
      acetylcholine receptor (nAChR). It has been well documented that nAChRs respond
      to chronic nicotine exposure by up-regulation of receptor numbers, which may
      underlie some aspects of nicotine addiction. In order to investigate the
      mechanism of nicotine-induced nAChR up-regulation, we have developed a cell
      culture system to assess membrane trafficking and nicotine-induced up-regulation
      of surface-expressed alpha(4)beta(2) nAChRs. Previous reports have implicated
      stabilization of the nAChRs at the plasma membrane as the potential mechanism of
      up-regulation. We have found that whereas nicotine exposure results in up
      regulation of surface receptors in our system, it does not alter surface receptor
      internalization from the plasma membrane, postendocytic trafficking, or lysosomal
      degradation. Instead, we find that transport of nAChRs through the secretory
      pathway to the plasma membrane is required for nicotine-induced up-regulation of
      surface receptors. Therefore, nicotine appears to regulate surface receptor
      levels at a step prior to initial insertion in the plasma membrane rather than by
      altering their endocytic trafficking or degradation rates as had been previously
      suggested.

PMID- 15741167
TI  - Connexin43 associated with an N-cadherin-containing multiprotein complex is
      required for gap junction formation in NIH3T3 cells.
AB  - Previous studies have indicated an intimate linkage between gap junction and
      adherens junction formation. It was suggested this could reflect the close
      membrane-membrane apposition required for junction formation. In NIH3T3 cells, we
      observed the colocalization of connexin43 (Cx43alpha1) gap junction protein with
      N-cadherin, p120, and other N-cadherin-associated proteins at regions of cell
      cell contact. We also found that Cx43alpha1, N-cadherin, and N-cadherin
      associated proteins were coimmunoprecipitated by antibodies to either Cx43alpha1,
      N-cadherin, or various N-cadherin-associated proteins. These findings suggest
      that Cx43alpha1 and N-cadherin are coassembled in a multiprotein complex
      containing various N-cadherin-associated proteins. Studies using siRNA knockdown
      indicated that cell surface expression of Cx43alpha1 required N-cadherin, and
      conversely, N-cadherin cell surface expression required Cx43alpha1. Pulse-chase
      labeling and cell surface biotinylation experiments indicated that in the absence
      of N-cadherin, Cx43alpha1 cell surface trafficking is blocked. Surprisingly,
      siRNA knockdown of p120, an N-cadherin-associated protein known to modulate cell
      surface turnover of N-cadherin, reduced N-cadherin cell surface expression
      without altering Cx43alpha1 expression. These observations suggest that in
      contrast to the coregulated cell surface trafficking of Cx43alpha1 and N
      cadherin, N-cadherin turnover at the cell surface may be regulated independently
      of Cx43alpha1. Functional studies showed gap junctional communication is reduced
      and cell motility inhibited with N-cadherin or Cx43alpha1 knockdown, consistent
      with the observed loss of both gap junction and cadherin contacts with either
      knockdown. Overall, these studies indicate that the intracellular coassembly of
      connexin and cadherin is required for gap junction and adherens junction
      formation, a process that likely underlies the intimate association between gap
      junction and adherens junction formation.

PMID- 15741169
TI  - Functional analysis of active site residues of the fosfomycin resistance enzyme
      FosA from Pseudomonas aeruginosa.
AB  - The metalloglutathione transferase FosA catalyzes the conjugation of glutathione
      to carbon-1 of the antibiotic fosfomycin, rendering it ineffective as an
      antibacterial drug. Codon randomization and selection for the ability of
      resulting clones to confer fosfomycin resistance to Escherichia coli were used to
      identify residues critical for FosA function. Of the 24 codons chosen for
      randomization, 16 were found to be essential because only the wild type amino
      acid was selected. These included ligands to the Mn(2+) and the K(+), residues
      that furnish hydrogen bonds to fosfomycin, and residues located in a putative
      glutathione/fosfomycin-binding site. The remaining eight positions randomized
      were tolerant to substitutions. Site-directed mutagenesis of some of the
      essential and tolerant amino acids to alanine was performed, and the activity of
      the purified proteins was determined. Mutation of the residues that are within
      hydrogen bonding distance to the oxirane or phosphonate oxygens of fosfomycin
      resulted in variants with very low or no activity. Mutation of Ser(94), which
      bridges one of the phosphonate oxygens with a potassium ion, resulted in
      insoluble protein. The Y39A mutation in the putative glutathione-binding site
      resulted in a 4-fold increase in the apparent K(m) for glutathione. Only two of
      the amino acids in the substrate-binding site are conserved in the related
      fosfomycin resistance proteins FosB and FosX, whereas no amino acids in the
      putative glutathione-binding site are conserved.

PMID- 15741170
TI  - Role of T-loop phosphorylation in PDK1 activation, stability, and substrate
      binding.
AB  - 3-Phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates the T-loop of
      several AGC (cAMP-dependent, cGMP-dependent, protein kinase C) family protein
      kinases, resulting in their activation. Previous structural studies have revealed
      that the alpha C-helix, located in the small lobe of the kinase domain of PDK1,
      is a key regulatory element, as it links a substrate interacting site termed the
      hydrophobic motif (HM) pocket with the phosphorylated Ser-241 in the T-loop. In
      this study we have demonstrated by mutational analysis that interactions between
      the phosphorylated Ser-241 and the alpha C-helix are not required for PDK1
      activity or substrate binding through the HM-pocket but are necessary for PDK1 to
      be activated or stabilized by a peptide that binds to this site. The structure of
      an inactive T-loop mutant of PDK1, in which Ser-241 is changed to Ala, was also
      determined. This structure, together with surface plasmon resonance binding
      studies, demonstrates that the PDK1(S241A)-inactive mutant possesses an intact HM
      pocket as well as an ordered alpha C-helix. These findings reveal that the
      integrity of the alpha C-helix and HM-pocket in PDK1 is not regulated by T-loop
      phosphorylation.

PMID- 15741171
TI  - Functional properties of endogenous receptor- and store-operated calcium influx
      channels in HEK293 cells.
AB  - Activation of phospholipase C (PLC)-mediated signaling pathways in non-excitable
      cells causes the release of calcium (Ca2+) from inositol 1,4,5-trisphosphate
      (InsP3)-sensitive intracellular Ca2+ stores and activation of Ca2+ influx via
      plasma membrane Ca2+ channels. The properties and molecular identity of plasma
      membrane Ca2+ influx channels in non-excitable cells is a focus of intense
      investigation. In the previous studies we used patch clamp electrophysiology to
      describe the properties of Ca2+ influx channels in human carcinoma A431 cell
      lines. Now we extend our studies to human embryonic kidney HEK293 cells. By using
      a combination of Ca2+ imaging and whole cell and single channel patch clamp
      recordings we discovered that: 1) HEK293 cells contain four types of plasma
      membrane Ca2+ influx channels: I(CRAC), Imin, Imax, and I(NS); 2) I(CRAC)
      channels are highly Ca2+-selective (P(Ca/Cs)>1000) and I(CRAC) single channel
      conductance is too small for single channel analysis; 3) Imin channels in HEK293
      cells display functional properties identical to Imin channels in A431 cells,
      with single channel conductance of 1.2 pS for divalent cations, 10 pS for
      monovalent cations, and divalent cation selectivity P(Ba/K)=20; 4) Imin channels
      in HEK293 cells are activated by InsP3 and inhibited by phosphatidylinositol 4,5
      bisphosphate, but store-independent; 5) when compared with Imin, Imax channels
      have higher conductance for divalent (17 pS) and monovalent (33 pS) cations, but
      less selective for divalent cations (P(Ba/K)=4), 6) Imax channels in HEK293 cells
      can be activated by InsP3 or by Ca2+ store depletion; 7) I(NS) channels are non
      selective (P(Ba/K)=0.4) and display a single channel conductance of 5 pS; and 8)
      I(NS) channels are not gated by InsP3 but activated by depletion of intracellular
      Ca2+ stores. Our findings provide novel information about endogenous Ca2+
      channels supporting receptor-operated and store-operated Ca2+ influx pathways in
      HEK293 cells.

PMID- 15741172
TI  - Disturbance of sphingolipid biosynthesis abrogates the signaling of Mss4,
      phosphatidylinositol-4-phosphate 5-kinase, in yeast.
AB  - The functional relationships between phosphoinositides and sphingolipids have not
      been well characterized to date. ISP-1/myriocin is a potent inhibitor of
      sphingolipid biosynthesis and induces severe growth defects in eukaryotic cells
      because of the sphingolipid deprivation. We characterized a novel multicopy
      suppressor gene of ISP-1-mediated cell death in yeast, MSS4. MSS4 encodes a
      phosphatidylinositol-4-phosphate 5-kinase that synthesizes phosphatidylinositol
      (4,5)-bisphosphate (PI4,5P(2)). We demonstrate here that ISP-1 treatment of yeast
      causes defects both in the activity and subcellular localization of Mss4. The
      effect of the Mss4 defect on the downstream signaling was examined, because
      interaction between the Mss4 product, PI4,5P(2), and the pleckstrin-homology
      domain of Rom2 mediates recruitment of Rom2 to the membrane, which is the crucial
      step for subsequent Rho1/2 activation. Indeed, failure of Rom2 recruitment was
      observed in ISP-1-treated cells as well as in csg2-deleted cells, which have
      reduced mannosylated inositolphosphorylceramide. These data suggested that proper
      sphingolipids are required for the signaling pathway involving Mss4.

PMID- 15741173
TI  - The activation of exocytotic sites by the formation of phosphatidylinositol 4,5
      bisphosphate microdomains at syntaxin clusters.
AB  - Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor component of the
      lipid bilayer but plays an important role in various cellular functions,
      including exocytosis and endocytosis. Recently, PI(4,5)P2 was shown to form
      microdomains in the plasma membrane. In this study, we investigated the
      relationship between the spatial organization of PI(4,5)P2 microdomains and
      exocytotic machineries in clonal rat pheochromocytoma PC12 cells. Both PI(4,5)P2
      and syntaxin, a soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor protein essential for exocytosis, exhibited punctate clusters in
      isolated plasma membranes. The number of PI(4,5)P2 microdomains colocalizing with
      syntaxin clusters and large dense core vesicles (LDCVs) was decreased after
      catecholamine release. Alternatively, the expression of type I
      phosphatidylinositol-4-phosphate 5-kinase (PIP5KI) increased the number of
      PI(4,5)P2 microdomains at syntaxin clusters with docked LDCVs and enhanced
      exocytotic activity, possibly by increasing the number of release sites. About
      half of the PI(4,5)P2 microdomains were not colocalized with Thy-1, a specific
      marker of lipid rafts, and the colocalization of transfected PIP5KI with syntaxin
      clusters was observed. These results suggest that the formation of PI(4,5)P2
      microdomains at syntaxin clusters with docked LDCVs is essential for Ca2+
      dependent exocytosis.

PMID- 15741174
TI  - Reconstitution of Nup157 and Nup145N into the Nup84 complex.
AB  - About 30 different nucleoporins (Nups) constitute the nuclear pore complex. We
      have affinity-purified 28 of these nuclear pore proteins and identified new
      nucleoporin interactions by this analysis. We found that Nup157 and Nup170, two
      members of the large structural Nups, and the Gly-Leu-Phe-Gly nucleoporin Nup145N
      specifically co-purified with members of the Nup84 complex. In addition, Nup145N
      co-enriched during Nup157 purification. By in vitro reconstitution, we
      demonstrate that Nup157 and Nup145N form a nucleoporin subcomplex. Moreover, we
      show that Nup157 and Nup145N bind to the heptameric Nup84 complex. This assembly
      thus represents approximately one-third of all nucleoporins. To characterize
      Nup157 structurally, we purified and analyzed it by electron microscopy. Nup157
      is a hollow sphere that resembles a clamp or a gripping hand. Thus, we could
      reconstitute an interaction between a large structural Nup, an FG repeat Nup, and
      a major structural module of the nuclear pore complex.

PMID- 15741175
TI  - Cell signaling through the protein kinases cAMP-dependent protein kinase, protein
      kinase Cepsilon, and RAF-1 regulates amphotropic murine leukemia virus envelope
      protein-induced syncytium formation.
AB  - Amphotropic murine leukemia virus (A-MuLV) utilizes the PiT2 sodium-dependent
      phosphate transporter as its cell surface receptor to infect mammalian cells. The
      process of A-MuLV infection requires cleavage of the R peptide from the envelope
      protein. This occurs within virions thereby rendering them competent to fuse with
      target cells. Envelope proteins lacking the inhibitory R peptide (e.g. envelope
      (R-) proteins) induce viral envelope-mediated cell-cell fusion (syncytium). Here
      we have performed studies to determine if cell signaling through protein kinases
      is involved in the regulation of PiT2-mediated A-MuLV envelope (R-)-induced
      syncytium formation. Truncated A-MuLV retroviral envelope protein lacking the
      inhibitory R peptide (R-) was used to induce viral envelope-mediated cell-cell
      fusion. Signaling through cyclic AMP to activate PKA was found to inhibit
      envelope-induced cell-cell fusion, whereas treatment of cells with PKA inhibitors
      H89, KT5720, and PKA Catalpha siRNA all enhanced this cell fusion process. It was
      noted that activation of PKC, as well as overexpression of PKCepsilon, up
      regulated A-MuLV envelope protein-induced cell-cell fusion, whereas exposure to
      PKC inhibitors and expression of a kinase-inactive dominant-negative mutant of
      PKCepsilon (K437R) inhibited syncytium formation. v-ras transformed NIH3T3 cells
      were highly susceptible to A-MuLV envelope-induced cell-cell fusion, whereas
      expression of a dominant-negative mutant of Ras (N17Ras) inhibited this cell
      fusion process. Importantly, activation of Raf-1 protein kinase also is required
      for A-MuLV envelope-induced syncytium formation. Expression of constitutively
      active BXB Raf supported, whereas expression of a dominant-negative mutant of Raf
      1 (Raf301) blocked, A-MuLV-induced cell-cell fusion. These results indicate that
      specific cell signaling components are involved in regulating PiT2-mediated A
      MuLV-induced cell-cell fusion. Selective pharmacological modulation of these
      signaling components may be an effective means of altering cell susceptibility to
      viral-mediated cytopathic effects.

PMID- 15741176
TI  - An efficient system to establish multiple embryonic stem cell lines carrying an
      inducible expression unit.
AB  - The growing use of mouse embryonic stem (ES) cells in research emphasizes their
      importance in studies of molecular mechanisms that maintain pluripotency and
      direct cellular differentiation. Although systems for regulatable transgene
      expression are essential for fine analysis of cellular processes at the molecular
      level, a strategy for the establishment of multiple ES cell lines carrying any of
      these systems has not yet been described. Here, we report our development of the
      ROSA-TET system, an effective system for the establishment of multiple ES cell
      lines carrying a tetracycline (Tc)-regulatable transgene at the Gt (ROSA)26asSor
      (ROSA26) locus. This system contains a knock-in step of a construct carrying both
      loxP and its mutant sequences into the ROSA26 locus, followed by a subsequent
      exchange step that introduces a cDNA to be Tc-regulated to the locus using the
      recombinase-mediated cassette exchange reaction. Both steps are demonstrated to
      give desired clones with high efficiency, suggesting that this system can be
      introduced readily into any ES cell lines, leading to the simultaneous
      establishment of multiple cell lines carrying different Tc-regulated cDNAs. We
      believe that use of this system will strongly accelerate molecular biological
      research using ES cells.

PMID- 15741177
TI  - Tagging genes with cassette-exchange sites.
AB  - In an effort to make transgenesis more flexible and reproducible, we developed a
      system based on novel 5' and 3' 'gene trap' vectors containing heterospecific Flp
      recognition target sites and the corresponding 'exchange' vectors allowing the
      insertion of any DNA sequence of interest into the trapped locus. Flp-recombinase
      mediated cassette exchange was demonstrated to be highly efficient in our system,
      even in the absence of locus-specific selection. The feasibility of constructing
      a library of ES cell clones using our gene trap vectors was tested and a thousand
      insertion sites were characterized, following electroporation in ES cells, by
      RACE-PCR and sequencing. We validated the system in vivo for two trapped loci in
      transgenic mice and demonstrated that the reporter transgenes inserted into the
      trapped loci have an expression pattern identical to the endogenous genes. We
      believe that this system will facilitate in vivo studies of gene function and
      large-scale generation of mouse models of human diseases, caused by not only loss
      but also gain of function alleles.

PMID- 15741178
TI  - Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H
      activity by hydroxylated tropolones.
AB  - High-throughput screening of a National Cancer Institute library of pure natural
      products identified the hydroxylated tropolone derivatives beta-thujaplicinol
      (2,7-dihydroxy-4-1(methylethyl)-2,4,6-cycloheptatrien-1-one) and manicol (1,2,3,4
      tetrahydro-5-7-dihydroxy-9-methyl-2-(1-methylethenyl)-6H-benzocyclohepten-6-one)
      as potent and selective inhibitors of the ribonuclease H (RNase H) activity of
      human immunodeficiency virus-type 1 reverse transcriptase (HIV-1 RT). beta
      Thujaplicinol inhibited HIV-1 RNase H in vitro with an IC50 of 0.2 microM, while
      the IC50 for Escherichia coli and human RNases H was 50 microM and 5.7 microM,
      respectively. In contrast, the related tropolone analog beta-thujaplicin (2
      hydroxy-4-(methylethyl)-2,4,6-cycloheptatrien-1-one), which lacks the 7-OH group
      of the heptatriene ring, was inactive, while manicol, which possesses a 7-OH
      group, inhibited HIV-1 and E.coli RNases H with IC50 = 1.5 microM and 40 microM,
      respectively. Such a result highlights the importance of the 2,7-dihydroxy
      function of these tropolone analogs, possibly through a role in metal chelation
      at the RNase H active site. Inhibition of HIV-2 RT-associated RNase H indirectly
      indicates that these compounds do not occupy the nonnucleoside inhibitor-binding
      pocket in the vicinity of the DNA polymerase domain. Both beta-thujaplicinol and
      manicol failed to inhibit DNA-dependent DNA polymerase activity of HIV-1 RT at a
      concentration of 50 microM, suggesting that they are specific for the C-terminal
      RNase H domain, while surface plasmon resonance studies indicated that the
      inhibition was not due to intercalation of the analog into the nucleic acid
      substrate. Finally, we have demonstrated synergy between beta-thujaplicinol and
      calanolide A, a nonnucleoside inhibitor of HIV-1 RT, raising the possibility that
      both enzymatic activities of HIV-1 RT can be simultaneously targeted.

PMID- 15741180
TI  - Molecular characterization of Drosophila NELF.
AB  - NELF and DSIF act together to inhibit transcription elongation in vitro, and are
      implicated in causing promoter proximal pausing on the hsp70 gene in Drosophila.
      Here, further characterization of Drosophila NELF is provided. Drosophila NELF
      has four subunits similar to subunits of human NELF. The amino acid sequences of
      NELF-B and NELF-D are highly conserved throughout their lengths, while NELF-A and
      NELF-E contain nonconserved regions inserted between conserved N- and C-terminal
      regions. Immunodepletion of NELF or DSIF from a nuclear extract desensitizes
      transcription in vitro to DRB. Immunodepletion of NELF also impairs promoter
      proximal pausing on the hsp70 promoter in vitro without affecting initiation.
      Chromatin immunoprecipitation analyses detect NELF at the promoters of the hsp70
      and beta1-tubulin genes where promoter proximal pausing has been previously
      detected. Heat shock induction of hsp70 results in a marked decrease in NELF at
      the hsp70 promoter. Immunofluorescence analysis of polytene chromosomes shows
      extensive colocalization of the NELF-B and NELF-D subunits at hundreds of
      interbands. Neither subunit appears to be recruited to puffs. These results
      provide a foundation for genetic and biochemical analysis of NELF in Drosophila.

PMID- 15741179
TI  - The contribution of phosphate-phosphate repulsions to the free energy of DNA
      bending.
AB  - DNA bending is important for the packaging of genetic material, regulation of
      gene expression and interaction of nucleic acids with proteins. Consequently, it
      is of considerable interest to quantify the energetic factors that must be
      overcome to induce bending of DNA, such as base stacking and phosphate-phosphate
      repulsions. In the present work, the electrostatic contribution of phosphate
      phosphate repulsions to the free energy of bending DNA is examined for 71 bp
      linear and bent-form model structures. The bent DNA model was based on the
      crystallographic structure of a full turn of DNA in a nucleosome core particle. A
      Green's function approach based on a linear-scaling smooth conductor-like
      screening model was applied to ascertain the contribution of individual phosphate
      phosphate repulsions and overall electrostatic stabilization in aqueous solution.
      The effect of charge neutralization by site-bound ions was considered using Monte
      Carlo simulation to characterize the distribution of ion occupations and
      contribution of phosphate repulsions to the free energy of bending as a function
      of counterion load. The calculations predict that the phosphate-phosphate
      repulsions account for approximately 30% of the total free energy required to
      bend DNA from canonical linear B-form into the conformation found in the
      nucleosome core particle.

PMID- 15741181
TI  - Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or
      transferase domains of REV1.
AB  - REV1 is central to the DNA damage response of eukaryotes through an as yet poorly
      understood role in translesion synthesis. REV1 is a member of the Y-type DNA
      polymerase family and is capable of in vitro deoxycytidyl transferase activity
      opposite a range of damaged bases. However, non-catalytic roles for REV1 have
      been suggested by the Saccharomyces cerevisiae rev1-1 mutant, which carries a
      point mutation in the N-terminal BRCT domain, and the recently demonstrated
      ability of the mammalian protein to interact with each of the other translesion
      polymerases via its extreme C-terminus. Here, we show that a region adjacent to
      this polymerase interacting domain mediates an interaction with PCNA. These C
      terminal domains of REV1 are necessary, although not sufficient, for effective
      tolerance of DNA damage in the avian cell line DT40, while the BRCT domain and
      transferase activity are not directly required. Together these data provide
      strong support for REV1 playing an important non-catalytic role in coordinating
      translesion synthesis. Further, unlike in budding yeast, rad18 is not epistatic
      to rev1 for DNA damage tolerance suggesting that REV1 and RAD18 play largely
      independent roles in the control of vertebrate translesion synthesis.

PMID- 15741182
TI  - Antisense inhibition of human miRNAs and indications for an involvement of miRNA
      in cell growth and apoptosis.
AB  - Of the over 200 identified mammalian microRNAs (miRNAs), only a few have known
      biological activity. To gain a better understanding of the role that miRNAs play
      in specific cellular pathways, we utilized antisense molecules to inhibit miRNA
      activity. We used miRNA inhibitors targeting miR-23, 21, 15a, 16 and 19a to test
      efficacy of antisense molecules in reducing miRNA activity on reporter genes
      bearing miRNA-binding sites. The miRNA inhibitors de-repressed reporter gene
      activity when a miRNA-binding site was cloned into its 3'-untranslated region. We
      employed a library of miRNA inhibitors to screen for miRNA involved in cell
      growth and apoptosis. In HeLa cells, we found that inhibition of miR-95, 124,
      125, 133, 134, 144, 150, 152, 187, 190, 191, 192, 193, 204, 211, 218, 220, 296
      and 299 caused a decrease in cell growth and that inhibition of miR-21 and miR-24
      had a profound increase in cell growth. On the other hand, inhibition of miR-7,
      19a, 23, 24, 134, 140, 150, 192 and 193 down-regulated cell growth, and miR-107,
      132, 155, 181, 191, 194, 203, 215 and 301 increased cell growth in lung carcinoma
      cells, A549. We also identified miRNA that when inhibited increased the level of
      apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased
      apoptosis (miR-214) in HeLa cells. From these screens, we conclude that miRNA
      mediated regulation has a complexity of cellular outcomes and that miRNAs can be
      mediators of regulation of cell growth and apoptosis pathways.

PMID- 15741183
TI  - Leaky ribosomal scanning in mammalian genomes: significance of histone H4
      alternative translation in vivo.
AB  - Like alternative splicing, leaky ribosomal scanning (LRS), which occurs at
      suboptimal translational initiation codons, increases the physiological
      flexibility of the genome by allowing alternative translation. Comprehensive
      analysis of 22 208 human mRNAs indicates that, although the most important
      positions relative to the first nucleotide of the initiation codon, -3 and +4,
      are usually such that support initiation (A-3 = 42%, G-3 = 36% and G+4 = 47%),
      only 37.4% of the genes adhere to the purine (R)-3/G+4 rule at both positions
      simultaneously, suggesting that LRS may occur in some of the remaining (62.6%)
      genes. Moreover, 12.5% of the genes lack both R-3 and G+4, potentially leading to
      sLRS. Compared with 11 genes known to undergo LRS, 10 genes with experimental
      evidence for high fidelity A+1T+2G+3 initiation codons adhered much more strongly
      to the R-3/G+4 rule. Among the intron-less histone genes, only the H3 genes
      adhere to the R-3/G+4 rule, while the H1, H2A, H2B and H4 genes usually lack
      either R-3 or G+4. To address in vivo the significance of the previously
      described LRS of H4 mRNAs, which results in alternative translation of the
      osteogenic growth peptide, transgenic mice were engineered that ubiquitously and
      constitutively express a mutant H4 mRNA with an A+1T+1 mutation. These transgenic
      mice, in particular the females, have a high bone mass phenotype, attributable to
      increased bone formation. These data suggest that many genes may fulfill cryptic
      functions by LRS.

PMID- 15741185
TI  - Human pol II promoter prediction: time series descriptors and machine learning.
AB  - Although several in silico promoter prediction methods have been developed to
      date, they are still limited in predictive performance. The limitations are due
      to the challenge of selecting appropriate features of promoters that distinguish
      them from non-promoters and the generalization or predictive ability of the
      machine-learning algorithms. In this paper we attempt to define a novel approach
      by using unique descriptors and machine-learning methods for the recognition of
      eukaryotic polymerase II promoters. In this study, non-linear time series
      descriptors along with non-linear machine-learning algorithms, such as support
      vector machine (SVM), are used to discriminate between promoter and non-promoter
      regions. The basic idea here is to use descriptors that do not depend on the
      primary DNA sequence and provide a clear distinction between promoter and non
      promoter regions. The classification model built on a set of 1000 promoter and
      1500 non-promoter sequences, showed a 10-fold cross-validation accuracy of 87%
      and an independent test set had an accuracy >85% in both promoter and non
      promoter identification. This approach correctly identified all 20 experimentally
      verified promoters of human chromosome 22. The high sensitivity and selectivity
      indicates that n-mer frequencies along with non-linear time series descriptors,
      such as Lyapunov component stability and Tsallis entropy, and supervised machine
      learning methods, such as SVMs, can be useful in the identification of pol II
      promoters.

PMID- 15741184
TI  - A family of RS domain proteins with novel subcellular localization and
      trafficking.
AB  - We report the sequence, conservation and cell biology of a novel protein, Psc1,
      which is expressed and regulated within the embryonic pluripotent cell population
      of the mouse. The Psc1 sequence includes an RS domain and an RNA recognition
      motif (RRM), and a sequential arrangement of protein motifs that has not been
      demonstrated for other RS domain proteins. This arrangement was conserved in a
      second mouse protein (BAC34721). The identification of Psc1 and BAC34721
      homologues in vertebrates and related proteins, more widely throughout evolution,
      defines a new family of RS domain proteins termed acidic rich RS (ARRS) domain
      proteins. Psc1 incorporated into the nuclear speckles, but demonstrated novel
      aspects of subcellular distribution including localization to speckles proximal
      to the nuclear periphery and localization to punctate structures in the cytoplasm
      termed cytospeckles. Integration of Psc1 into cytospeckles was dependent on the
      RRM. Cytospeckles were dynamic within the cytoplasm and appeared to traffic into
      the nucleus. These observations suggest a novel role in RNA metabolism for ARRS
      proteins.

PMID- 15741186
TI  - Alpha2(I) collagen gene regulation by protein kinase C signaling in human dermal
      fibroblasts.
AB  - We investigated the mechanisms by which protein kinase C (PKC) regulates the
      expression of the alpha2(I) collagen gene in normal dermal fibroblasts. Reduction
      of PKC-alpha activity by treatment with Go697-6 or by overexpression of a
      dominant negative (DN) mutant form decreased alpha2(I) collagen gene expression.
      This decrease required a sequence element in the collagen promoter that contains
      Sp1/Sp3 binding sites. Reduction of PKC-delta activity by rottlerin or
      overexpression of DN PKC-delta also decreased alpha2(I) collagen gene expression.
      This effect required a separate sequence element containing Sp1/Sp3-binding sites
      and an Ets-binding site. In both cases, point mutations within the response
      elements abrogated the response to PKC inhibition. Forced overexpression of Sp1
      rescued the PKC inhibitor-mediated reduction in collagen protein expression. A
      DNA affinity precipitation assay revealed that inhibition of PKC-delta by
      rottlerin increased the binding activity of endogenous Fli1 and decreased that of
      Ets1. On the other hand, TGF-beta1, which increased the expression of PKC-delta,
      had the opposite effect, increasing the binding activity of Ets1 and decreasing
      that of Fli1. Our results suggest that PKC-delta is involved in the regulation of
      the alpha2(I) collagen gene in the presence or absence of TGF-beta. Alteration of
      the balance of Ets1 and Fli1 may be a novel mechanism regulating alpha2(I)
      collagen expression.

PMID- 15741187
TI  - Mithramycin forms a stable dimeric complex by chelating with Fe(II): DNA
      interacting characteristics, cellular permeation and cytotoxicity.
AB  - Mith (mithramycin) forms a 2:1 stoichiometry drug-metal complex through the
      chelation with Fe(II) ion as studied using circular dichroism spectroscopy. The
      binding affinity between Mith and Fe(II) is much greater than other divalent
      metal ions, including Mg(II), Zn(II), Co(II), Ni(II) and Mn(II). The [(Mith)2
      Fe(II)] complex binds to DNA and induces a conformational change of DNA. Kinetic
      analysis of surface plasmon resonance studies revealed that the [(Mith)2-Fe(II)]
      complex binds to DNA duplex with higher affinity compared with the [(Mith)2
      Mg(II)] complex. A molecular model of the Mith-DNA-Metal(II) complex is
      presented. DNA-break assay showed that the [(Mith)2-Fe(II)] complex was capable
      of promoting the one-strand cleavage of plasmid DNA in the presence of hydrogen
      peroxide. Intracellular Fe(II) assays and fluorescence microscopy studies using
      K562 indicated that this dimer complex maintains its structural integrity and
      permeates into the inside of K562 cells, respectively. The [(Mith)2-Fe(II)]
      complex exhibited higher cytotoxicity than the drug alone in some cancer cell
      lines, probably related to its higher DNA-binding and cleavage activity.
      Evidences obtained in this study suggest that the biological effects caused by
      the [(Mith)2-Fe(II)] complex may be further explored in the future.

PMID- 15741189
TI  - Training professionals to engage with and promote self-management.
AB  - We have set out to investigate an approach to improve patients' ability to self
      manage chronic illness. For effective health care in chronic disease, we believe
      patients need to work in partnership with their doctor; patient-centred
      consultations are one way to achieve this. This report describes our experience
      of training specialists in gastroenterology to consult in a patient-centred style
      as part of a complex self-management intervention in a randomized controlled
      trial (RCT) involving 700 patients with established inflammatory bowel disease
      (IBD) attending outpatient clinics. The training session aimed to provide
      specialists from nine randomly selected intervention sites with the basic skills
      to carry out the intervention. The training lasted 2 hours, and included
      background on the research and intervention, a demonstration video, role-play,
      and video-feedback training. The main findings of the RCT are presented (service
      use, enablement and satisfaction), and discussed in the light of the views of
      consultants and patients on the experience of putting the training into practice.
      The findings of our study confirm and highlight the value of training in patient
      centred communication and its potential for promoting self-management effects;
      the training proved effective in enabling consultants in gastroenterology to
      establish guided self-management in patients with IBD.

PMID- 15741190
TI  - Diagnosing Kawasaki syndrome: the need for a new clinical tool.

PMID- 15741188
TI  - Estimate of deaths attributable to passive smoking among UK adults: database
      analysis.
AB  - OBJECTIVE: To estimate deaths from passive smoking in employees of the
      hospitality industry as well as in the general workforce and general population
      of the United Kingdom. DESIGN: Calculation, using the formula for population
      attributable proportion, of deaths likely to have been caused by passive smoking
      at home and at work in the UK according to occupation. Sensitivity analyses to
      examine impact of varying assumptions regarding prevalence and risks of exposure.
      SETTING: National UK databases of causes of death, employment, structure of
      households, and prevalences of active and passive smoking. MAIN OUTCOME MEASURES:
      Estimates of deaths due to passive smoking according to age group (< 65 or > or =
      65) and site of exposure (domestic or workplace). RESULTS: Across the United
      Kingdom as a whole, passive smoking at work is likely to be responsible for the
      deaths of more than two employed people per working day (617 deaths per year),
      including 54 deaths in the hospitality industry each year. Each year passive
      smoking at home might account for another 2700 deaths in persons aged 20-64 years
      and 8000 deaths among people aged > or = 65. CONCLUSION: Exposure at work might
      contribute up to one fifth of all deaths from passive smoking in the general
      population aged 20-64 years, and up to half of such deaths among employees of the
      hospitality industry. Adoption of smoke free policies in all workplaces and
      reductions in the general prevalence of active smoking would lead to substantial
      reductions in these avoidable deaths.

PMID- 15741191
TI  - Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To evaluate bone mineral status over 1 yr of etanercept treatment in
      juvenile idiopathic arthritis (JIA). METHODS: Twenty children (13 female, 7 male)
      aged 5.2-11.4 yr, with active polyarticular JIA were prospectively enrolled to
      receive etanercept (0.4 mg/kg, twice weekly). Responders were defined according
      to the American College of Rheumatology Pediatric 50 definition of improvement.
      Broadband ultrasound attenuation (BUA) by bone was determined at the left
      calcaneus to assess bone status at baseline and at 1-yr follow-up. RESULTS: After
      12 months of treatment, 15 (75%) patients were considered as responders. At
      baseline, responders and non-responders did not differ with regard to age,
      disease duration, core-set variables or BUA and Z-score values (patient's value-
      age specific normal value/normal group's s.d.). At 6-month and 1-yr follow-up in
      the whole group, BUA and Z-score values were not significantly different compared
      with baseline. At 1-yr follow-up, but not at 6 months, all 15 responders,
      differently from non-responders, showed a significant increase in both BUA and Z
      score values: BUA at 1 yr 55.2 +/- 3.3 vs baseline 43.5 +/- 3.2 dB/MHz, P<0.001;
      Z score at 1 yr -0.3 +/- 0.2 vs baseline 1.5 +/- 0.4, P<0.002. CONCLUSION: For
      the first time in childhood rheumatic disease this pilot prospective study,
      although in a small group, shows evidence that 1 yr of etanercept therapy by
      controlling the underlying disease activity induces a sustained benefit on JIA
      bone loss. Prospective studies in larger patient samples are needed to confirm
      these data.

PMID- 15741192
TI  - Ultrasonographic changes of major salivary glands in primary Sjogren's syndrome.
      Diagnostic value of a novel scoring system.
AB  - OBJECTIVES: To reveal typical ultrasonographic (US) changes in major salivary
      glands associated with Sjogren's syndrome (SS) and to determine the diagnostic
      value of a novel US scoring system. METHODS: In 218 consecutive patients with
      suspected SS, US of both parotid and submandibular salivary glands was performed
      besides the regular diagnostic procedure following the American-European
      Consensus Group criteria of 2002. Five US parameters were assessed: echogenicity,
      inhomogeneity, number of hypoechogenic areas, the hyperechogenic reflections and
      clearness of the borders of the salivary gland. The grades of these five
      parameters for all four salivary glands were summed. The final US score ranged
      from 0 to 48. RESULTS: SS was established in 68 patients. The remaining 150
      subjects, in whom SS was not confirmed, constituted our control group. All five
      US parameters were significantly associated with SS. The patients with SS had
      significantly higher US scores than those not diagnosed with SS (P<0.01). Setting
      the cut-off US score at 17 resulted in the best ratio of specificity (98.7%) to
      sensitivity (58.8%). CONCLUSIONS: Well-defined US changes in the major salivary
      glands summarized in our novel scoring system were typical of SS patients.
      Advanced structural changes found on US imaging almost invariably represent SS
      salivary gland involvement.

PMID- 15741193
TI  - Beliefs about medications: a questionnaire survey of people with rheumatoid
      arthritis.
AB  - OBJECTIVES: To investigate beliefs about medications held by people with
      rheumatoid arthritis (RA), what factors are related to these specific medication
      beliefs, and whether these beliefs influence adherence. METHODS: The design was a
      cross-sectional postal questionnaire survey of people with RA. The Beliefs about
      Medicines Questionnaire was used to assess beliefs about the necessity of
      medication and concerns about it. Questionnaires were mailed to 600 out-patients
      with RA. RESULTS: The response rate was 57.3%. Most (74.3%) respondents agreed or
      strongly agreed that their arthritis medications are necessary for their health.
      However, 47.4% were concerned about potential adverse consequences. The overall
      necessity score (mean 19.2, s.d. 3.13) was higher than the concerns score (mean
      15.84, s.d. 3.53; P<0.001). Greater disability was associated with higher
      necessity scores (r = 0.36; P<0.001). Greater helplessness correlated with higher
      concerns scores (r = 0.49; P<0.001). There was no association between RA
      knowledge and beliefs about medications (necessity scale, r = 0.02, P = 0.66;
      concerns scale, r=-0.08, P = 0.14). Concerns scores for non-adherent participants
      (mean 17.88, s.d. 3.29) were higher than for the adherent group (mean 15.64, s.d.
      3.51; P = 0.002). CONCLUSIONS: Most people with RA have positive beliefs about
      the necessity of their medication. However, levels of concern are high and
      associate with helplessness and non-adherence. The Beliefs about Medicines
      Questionnaire may identify people at risk of poor adherence and provide a focus
      for patients to discuss their beliefs, providing opportunities to improve
      adherence.

PMID- 15741194
TI  - Is it time for more rheumatologists to embrace osteoarthritis?

PMID- 15741195
TI  - A role for TARC/CCL17, a CC chemokine, in New Zealand mice.

PMID- 15741196
TI  - Study of undifferentiated spondyloarthropathy among first-degree relatives of
      ankylosing spondylitis probands.
AB  - OBJECTIVE: To estimate in a Chinese population the prevalence of undifferentiated
      spondyloarthropathy (USpA) among first-degree relatives (FDRs) of ankylosing
      spondylitis (AS) probands, and to compare the clinical features of familial USpA
      with those of sporadic USpA. METHODS: The FDRs of two separate cohorts of
      consecutive AS probands were evaluated for the prevalence of USpA, using the
      Modified New York criteria and the European Spondylitis Study Group criteria for
      AS and SpA, respectively. Sporadic USpA and FDRs of non-SpA rheumatic patient
      probands served as separate controls. RESULTS: Among the 301 FDRs of 102 AS
      probands, 7.0% were USpA. This was 1000 times higher than the 147 FDRs of 40 non
      SpA probands (P = 0.00230). Within the AS families, USpA was less male-dominated
      than AS (33.3 vs 72.5%) (P = 0.006). The only feature distinguishing familial
      from sporadic USpA was that the percentages of HLA B27 were 100 and 50%,
      respectively (P<0.001). CONCLUSION: USpA and AS coexist in the same Chinese
      families, both being predisposed by HLA B27. In these families, a female gender
      favours the development of USpA rather than AS. A significant subset of sporadic
      USpA (HLA B27-negative group) has a different genetic predisposition compared
      with familial USpA.

PMID- 15741197
TI  - Effect of Tai Chi in adults with rheumatoid arthritis.

PMID- 15741198
TI  - TNF-blocking agents and tuberculosis: new drugs illuminate an old topic.
AB  - Newer TNF blockers (etanercept, infliximab and adalimumab) have contributed
      greatly to the control of chronic inflammatory disease. Many of the damaging
      inflammatory mechanisms that they inhibit are, however, important in maintaining
      tuberculosis in the latent phase (latent tuberculosis infection or LTBI). There
      is considerable evidence that links reactivation of LTBI to the use of anti-TNF
      monoclonal antibody (mAb) treatments, which appear to result in disruption of the
      granuloma that normally compartmentalizes but does not kill Mycobacterium
      tuberculosis during LTBI. This effect can be explained, in part, by directly
      neutralizing TNF, which plays a key role in tuberculosis immunity. To the
      clinician, dealing with LTBI in patients on these medications is an important
      issue. Prescribers should seek local expert help in this regard, as global LTBI
      treatment regimens differ. Nonetheless, screening for and treating LTBI will
      prevent reactivation in most patients. LTBI screening should include a careful
      history, tuberculin skin test and chest radiograph. Prophylactic treatment (e.g.
      isoniazid for 9 months) should be offered to patients with LTBI, in accordance
      with local advice. False-negative tuberculin skin test results can be expected in
      these patient groups. False-negative skin tests also mean that clinicians cannot
      be complacent about patients on TNF blockers who lack evidence of LTBI. On the
      contrary, because tuberculosis disease can be lethal, all treated patients should
      be advised to seek medical attention if symptoms suggestive of tuberculosis
      emerge. The indications for these successful agents are expanding, and efficient
      management of the LTBI issue should improve their safety profile.

PMID- 15741199
TI  - Quality of care for NSAID users: development of an assessment tool.
AB  - OBJECTIVE: Assessments of NSAID use based on authoritative guidelines typically
      overlook patients' views and nuances of medical history. Our objective was to
      develop an assessment tool that incorporates these aspects, and technical items,
      for quality of care assessments in NSAID users. METHODS: Patients newly referred
      to a university hospital were interviewed by a nurse using an agreed template. A
      multidisciplinary group of rheumatologists, nurse specialists, primary care
      physicians and a pharmacist reviewed current guidance and systematic reviews on
      NSAID use, and a series of interview transcripts. The group agreed, by informal
      consensus, important determinants of effective and safe NSAID use. Technical
      aspects of medical care and items that reflected interpersonal care were included
      in an index for assessing quality of care for individual patients. Interview
      transcripts of 100 patients were scored by panel members and reliability of
      scores was tested by calculating weighted percentage agreement and the kappa
      statistic. RESULTS: Our final index had five domains: medical risk factors; steps
      taken to reduce risk; knowledge of adverse effects; NSAID dose; and cost
      efficiency. Each item was scored 0, 1 or 2. Scores were summed, giving a maximum
      of 10 (low scores indicating low quality). Intra-rater agreement was >90%; kappa
      was 0.47-0.87 for individual domains and 0.59 for overall score. Inter-rater
      agreement for overall score was 95%; kappa was 0.25-0.78 for domains and 0.48 for
      overall score. Patients with especially low scores were identified using the mode
      of scores for five assessors; obvious clinical concerns were identified,
      supporting index face validity. CONCLUSIONS: A simple index to evaluate quality
      of care for NSAID users based on a patient interview is described. This may be
      used by one or more assessors to examine care standards and highlight
      deficiencies in relation to NSAID use in practice.

PMID- 15741200
TI  - Pathogenesis of Raynaud's phenomenon.
AB  - The pathogenesis of Raynaud's phenomenon is not fully understood. However, the
      last 20 yr have witnessed enormous increases in our understanding of different
      mechanisms which, singly or in combination, may contribute. A key point is that
      Raynaud's phenomenon can be either primary (idiopathic) or secondary to a number
      of underlying conditions, and that the pathogenesis and pathophysiology vary
      between these conditions. This review concentrates upon those subtypes of
      Raynaud's phenomenon of most interest to rheumatologists: systemic sclerosis
      related Raynaud's phenomenon, primary Raynaud's phenomenon and Raynaud's
      phenomenon secondary to hand-arm vibration syndrome. In this review, I shall
      discuss the main mechanisms thought to be important in pathophysiology under the
      three broad headings of 'vascular', 'neural' and 'intravascular'. While these are
      false distinctions because all interrelate, they facilitate discussion of the key
      elements: the blood vessel wall (particularly the endothelium), the neural
      control of vascular tone, and the many circulating factors which can impair blood
      flow and/or cause endothelial injury. Vascular abnormalities include those of
      both structure and function. Neural abnormalities include deficiency of the
      vasodilator calcitonin gene-related peptide (released from sensory afferents),
      alpha(2)-adrenoreceptor activation (possibly with up-regulation of the normally
      'silent' alpha(2C)-adrenoreceptor) and a central nervous system component.
      Intravascular abnormalities include platelet activation, impaired fibrinolysis,
      increased viscosity and probably oxidant stress. As our understanding of the
      pathophysiology of Raynaud's phenomenon increases, so do our possibilities for
      identifying effective treatments.

PMID- 15741201
TI  - Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to
      chromosome 9q33.2-q34.2 by total genome search for linkage.
AB  - BACKGROUND: Nephrolithiasis is a complex, multifactorial disease resulting from
      genetic and environmental interaction. The pathogenesis of nephrolithiasis is far
      from being understood. So far, no gene locus for autosomal dominant
      nephrolithiasis only has been described. We here identified a new suggestive gene
      locus for autosomal dominant nephrolithiasis by a genome-wide search for linkage
      in a Spanish kindred with nephrolithiasis. METHODS: Clinical data, blood and
      urine samples of 18 individuals from a Spanish kindred with nephrolithiasis were
      collected. We performed a genome-wide search for linkage using 380 polymorphic
      microsatellite markers. RESULTS: Nephrolithiasis segregated in this Spanish
      kindred in a pattern compatible with autosomal dominant inheritance. The total
      genome search yielded the highest two-point LOD score of Z(max) = 1.99 (theta =
      0) for marker D9S159 on chromosome 9q33.2-q34.2. Multipoint analysis of 24
      polymorphic markers used for further fine mapping resulted in a LOD score of
      Z(max) = 2.7 (theta = 0) for markers D9S1881-D9S164, thereby identifying a new
      gene locus for autosomal dominant nephrolithiasis (NPL1). Two recombination
      events define D9S1850 as the centromeric flanking marker and D9S1818 as the
      telomeric flanking marker, restricting the NPL1 locus to a 14 Mb interval.
      CONCLUSION: We here identified a new suggestive gene locus (NPL1) for autosomal
      dominant nephrolithiasis. It is localized on chromosome 9q33.2-q34.2. The
      identification of the responsible gene will provide new insights into the
      molecular basis of nephrolithiasis.

PMID- 15741202
TI  - The impact of anaemia and kidney function in congestive heart failure and
      preserved systolic function.
AB  - BACKGROUND: The importance of anaemia in chronic heart failure was highlighted
      recently by different cohort studies. The aim of this study was to assess the
      prevalence of anaemia and its relationship to renal function, left ventricular
      function and symptoms of heart failure. METHODS: We surveyed cases of patients
      admitted to the Department of Cardiology during 22 consecutive months. Laboratory
      measurements, blood pressure and echocardiographic parameters were obtained with
      standardized methods. RESULTS: Out of a total number of 2941 patients, 238
      patients (8.1%) had haemoglobin values <11 g/dl. There was a positive association
      of anaemia with the symptoms of heart failure with a lowering of the median
      haemoglobin from 14.2 g/dl [New York Heart Association (NYHA) I] to 12.9 g/dl
      (NYHA IV, P<0.001). Interestingly, anaemia was not associated with left
      ventricular function or any left ventricular parameters. Symptoms of heart
      failure, however, were associated with kidney function. The estimated glomerular
      filtration rate (GFR) was 82 ml/min at NYHA I and 59 ml/min at NYHA IV, P<0.05.
      There was an association between impaired renal function and haemoglobin values.
      Haemoglobin was 14.2 g/dl in the group with normal renal function and 11.1 g/dl
      in the group with a GFR <25 ml/min (P<0.001). Even in patients with normal renal
      function (878 patients, GFR >85 ml/min), we still found an association of anaemia
      with the symptoms of heart failure. Haemoglobin was 14.5 g/dl at NYHA I and 13.4
      g/dl at NYHA IV, P<0.0001. CONCLUSION: Anaemia is found in 8.1% of patients
      admitted to cardiology service. Anaemia was clearly associated with symptoms of
      congestive heart failure even in patients with normal renal function. Anaemia was
      not associated with left ventricular function.

PMID- 15741203
TI  - Combination therapy with sirolimus (rapamycin) and tacrolimus (FK-506) in
      treatment of refractory minimal change nephropathy, a clinical case report.

PMID- 15741204
TI  - Acute renal failure with severe loin pain and patchy renal ischaemia after
      anaerobic exercise (ALPE) (exercise-induced acute renal failure) in a father and
      child with URAT1 mutations beyond the W258X mutation.

PMID- 15741205
TI  - Pegylated interferon for the treatment of hepatitis C virus in haemodialysis
      patients.

PMID- 15741206
TI  - Subcellular distribution of Ras GTPase isoforms in normal human kidney.
AB  - BACKGROUND: Ras GTPase isoforms have been implicated in proliferative renal
      disease and are known to have differential cellular expression in kidney.
      However, their exact subcellular location in various cells is unknown. METHODS:
      Immunogold labelling for Ras isoforms (Harvey, Kirsten and Neural) was performed
      for subcellular localization under electron microscopy in fresh normal kidney
      specimens, obtained from the opposite pole of kidneys removed for renal cell
      cancer. RESULTS: There was prominent staining shown by Ha-Ras only on the
      glomerular foot processes as compared with basement membrane or the endothelial
      cells. Mesangial cells showed intense staining in the cytosol with Ha-Ras (absent
      in the nucleus), minimal staining with Ki-Ras and none with N-Ras. In both the
      proximal and distal convoluted tubules, there was a clear staining of the
      mitochondria with Ha-Ras, with mild cytosolic staining with all of the isoforms.
      CONCLUSIONS: Ras isoforms have distinct and separate subcellular distributions in
      normal kidney cells. Understanding the functional aspects of this distribution
      pattern is essential if Ras is to be targeted by genetic or molecular therapeutic
      tools.

PMID- 15741207
TI  - Elevated cardiac troponin T is associated with increased left ventricular mass
      index and predicts mortality in continuous ambulatory peritoneal dialysis
      patients.
AB  - BACKGROUND: Patients with end-stage renal disease have a high risk of premature
      death, which is due mainly to cardiovascular (CV) events. Elevated cardiac
      troponin T (cTnT) is related to increased left ventricular mass index (LVMI) and
      predicts poor outcome in chronic haemodialysis patients. We investigated the
      prognostic value of cTnT and its relationship with left ventricular mass in
      continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Sixty-five
      CAPD patients (mean age: 56+/-12 years; 36% males) with no evidence of acute
      coronary syndrome in 28 days prior to the study were examined prospectively.
      After 48 months of follow-up, we evaluated total and CV mortality. RESULTS:
      During follow-up, 23 patients (35%) died (70% CV causes, 22% infection, 4%
      tumour, 4% unknown). In univariate analysis, concentrations of cTnT >/=0.035
      ng/ml, increased LVMI, diabetes, serum albumin and age were all strong predictors
      of total mortality. In multivariate logistic regression analysis, cTnT >/=0.035
      ng/ml and age independently predicted total mortality [odds ratio (OR): 4.31; 95%
      confidence interval (95% CI): 1.16-16.04; P = 0.008 and OR: 1.08; 95% CI: 1.02
      1.15; P = 0.002, respectively]. cTnT level >/=0.035 ng/ml was the only
      independent predictor of CV mortality in multivariate logistic regression
      analysis (OR: 8.94; 95% CI: 2.23-35.88; P<0.005). There was a significant
      positive correlation between serum cTnT level and LVMI (rho = 0.41; P<0.002).
      Neither cTnI, CK nor CK-MB were related to total or CV mortality. CONCLUSIONS:
      Elevated serum cTnT but not cTnI predicted total and CV mortality in CAPD
      patients. Elevated cTnT levels were also associated with increased LVMI.

PMID- 15741209
TI  - Co-infection by cytomegalovirus and BK polyoma virus in renal allograft,
      mimicking acute rejection.

PMID- 15741210
TI  - Comparison of renal injury in myeloablative autologous, myeloablative allogeneic
      and non-myeloablative allogeneic haematopoietic cell transplantation.

PMID- 15741208
TI  - Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in
      renal transplantation: 2 year follow-up results.
AB  - BACKGROUND: Comparison studies of calcineurin inhibitors as cornerstone
      immunosuppressants in renal transplantation have demonstrated that tacrolimus
      consistently reduces acute rejection rates and, in some studies, also improves
      long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the
      present 2 year follow-up of the European Tacrolimus vs Cyclosporin A
      Microemulsion Renal Transplantation Study was to investigate long-term clinical
      outcome in terms of rate of acute rejection, graft and patient survival and graft
      function. METHODS: The European Tacrolimus vs Cyclosporin A Microemulsion Renal
      Transplantation Study was a randomized, comparative 6 month trial of the
      calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine
      and steroids. The intent-to-treat population (ITT) consisted of 286 patients in
      the tacrolimus arm and 271 in the CsA microemulsion (CsA-ME) arm. Whereas whole
      blood level targets were 10-20 and 5-15 ng/ml for tacrolimus and 100-400 and 100
      200 ng/ml for CsA during months 0-3 and 4-6, respectively, during the
      investigator-driven follow-up after termination of the main study (months 7-24)
      no specific calcineurin inhibitor target levels were required. Follow-up data
      were collected at 2 years post-transplantation from 237 (82.9% of the ITT
      population) patients who received tacrolimus and 222 (81.9% of the ITT
      population) patients who received CsA-ME. RESULTS: Calculated on ITT populations,
      mortality (2.0% vs 3.3%; P<0.05 in Kaplan-Meier analysis) was lower, but rate of
      graft loss (9.3% vs 11.2%; P = 0.12 in Kaplan-Meier analysis) was not
      significantly different after 2 years with tacrolimus- vs CsA-ME-based
      immunosuppression. Biopsy-proven acute rejection was significantly lower (19.6%)
      with tacrolimus than with CsA-ME (37.3%) during months 0-6 (P<0.0001), but was
      not significantly different during months 7-12 and 13-24 of follow-up (1.7% and
      0.8% with tacrolimus and 4.7% and 0.9% with CsA-ME, respectively). A composite
      endpoint consisting of graft loss, patient death and biopsy-proven acute
      rejection occurred significantly more frequently in CsA-ME patients than in
      tacrolimus patients (42.8% vs 25.9%; P<0.001) during 24 months follow-up. Renal
      function 2 years post-transplant, measured by serum creatinine concentrations,
      was significantly better in tacrolimus-based compared with CsA-ME-based
      immunosuppression (136.9 vs 161.6 micromol/l; P<0.01). Cornerstone
      immunosuppression remained unchanged in 82.5% and 66.2% of patients treated with
      tacrolimus and CsA-ME, respectively. At 2 years, more patients in the tacrolimus
      arm were off steroids and received calcineurin inhibitor monotherapy, and fewer
      tacrolimus patients remained on a triple immunosuppressive regimen. The
      cardiovascular risk profile was affected favourably in the tacrolimus arm, with
      lower cholesterol and triglyceride concentrations (despite less use of
      cholesterol-lowering drugs); no significant difference in requirement for
      antidiabetic medication was noted. CONCLUSIONS: The 2 year study results confirm
      that tacrolimus is a highly efficacious cornerstone immunosuppressant in kidney
      transplantation. Tacrolimus-based immunosuppression may induce long-term benefits
      with regard to graft function and graft survival. The overall side-effect profile
      is considered to be favourable.

PMID- 15741211
TI  - Doxycycline may reduce the incidence of aneurysms in haemodialysis vascular
      accesses.
AB  - BACKGROUND: Doxycycline can prevent aortic aneurysms through the inhibition of
      enzymes that degrade vessel walls. We investigated whether haemodialysis patients
      who had received one or more courses of doxycycline were at less risk for
      aneurysms in their vascular accesses than those who had received other
      antibiotics. METHODS: Three hundred and eight patients undergoing chronic
      maintenance hemodialysis were evaluated for aneurysm formation after exposure to
      doxycycline or another antibiotic. Conditional forward logistical analysis using
      Cox proportional hazards test (SPSS) was performed to determine the potential
      significance of differences of aneurysm formation between the two groups.
      RESULTS: Patients who had received doxycycline appeared to be at lower risk than
      the control group, but the effect was most obvious in those patients with
      synthetic grafts. CONCLUSIONS: Doxycycline may have the ability to reduce
      aneurysm formation in haemodialysis vascular accesses and a large prospective
      study is warranted.

PMID- 15741212
TI  - Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive
      HIV-1-infected patients. Data from a double-blind randomized active-controlled
      multicentre study.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) was developed for the treatment
      of human immunodeficiency virus (HIV) infection. However, controlled data are
      sparse on the long-term renal tolerability of TDF at the currently approved daily
      dose of 300 mg in treatment-naive HIV-infected patients. METHODS: Over 144 weeks,
      this 600 patient, multicentre randomized, placebo-controlled, double-blind trial
      compared stavudine (301 patients) and TDF (299 patients), both administered in
      combination with lamivudine and efavirenz, in antiretroviral-naive patients. TDF
      or placebo and stavudine or placebo were administered in an open-label fashion.
      All medications were taken orally. At screening, all patients had serum
      creatinines <1.5 mg/dl, calculated creatinine clearances > or =60 ml/min and a
      serum phosphorus > or =2.2 mg/dl. RESULTS: The incidences of grades 1 (> or =0.5
      mg/dl increase from baseline), 2 (2.1-3.0 mg/dl) and 3 (3.1-6.0 mg/dl) serum
      creatinine elevations at week 144 were 4, <1 and 0%, respectively, in the TDF
      group and 2, 0 and <1% in the stavudine control group (P = NS). There were no
      grade 4 (>6 mg/dl) serum creatinine elevations. At week 144, there was no change
      from baseline in the mean (0.83 mg/dl) serum creatinine in the TDF group compared
      with a 0.1 mg/dl decrease from baseline (0.83 mg/dl) in the stavudine control
      group. The incidences of grades 1 (2.0-2.2 mg/dl), 2 (1.5-1.9 mg/dl) and 3 (1.0
      1.4 mg/dl) hypophosphataemia at week 144 were 4, 3 and <1%, respectively, in the
      TDF group and 4, 2 and <1% in the control group (P = NS). No patient experienced
      grade 4 (<1.0 mg/dl) hypophosphataemia. At week 144, the decrease (Delta) of mean
      serum phosphorus levels from baseline in both groups was similar (Delta 0.2 from
      3.6 mg/dl for the TDF group, and 0.1 from 3.5 mg/dl for the stavudine control
      group). No patient developed Fanconi's syndrome or proximal renal tubular
      dysfunction during the study. CONCLUSION: Through 144 weeks, TDF and stavudine,
      each administered in combination with efavirenz and lamivudine, had similar renal
      safety profiles in treatment-naive HIV-infected patients with normal renal
      function at baseline.

PMID- 15741213
TI  - Renal vein thrombosis as a presenting symptom of multiple genetic pro-coagulant
      defects.

PMID- 15741214
TI  - Fibromodulin, an extracellular matrix protein: characterization of its unique
      gene and protein expression in B-cell chronic lymphocytic leukemia and mantle
      cell lymphoma.
AB  - Fibromodulin is an extracellular matrix protein normally produced by collagen
      rich tissues; the fibromodulin gene has been found to be the most overexpressed
      gene in B-cell chronic lymphocytic leukemia. In this study, fibromodulin was
      expressed at the gene level (reverse transcription-polymerase chain reaction [RT
      PCR]) in all patients with B-CLL (n = 75) and in most (5 of 7) patients with
      mantle cell lymphoma (MCL). No mutations in the fibromodulin gene were detected.
      Fibromodulin was also detected at the protein level in the cytoplasm of the B-CLL
      cells and in the supernatant after in vitro cultivation, but not at the cell
      surface. Fibromodulin was not found in patients with T-cell chronic lymphocytic
      leukemia (T-CLL), B-cell prolymphocytic leukemia (B-PLL), T-cell prolymphocytic
      leukemia (T-PLL), hairy cell leukemia, follicular lymphoma, lymphoplasmacytic
      lymphoma, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myelogenous
      leukemia (AML), or chronic myelogenous leukemia (CML) or in 36 hematologic cell
      lines. Normal blood mononuclear cells (T and B lymphocytes, monocytes), tonsil B
      cells, and granulocytes did not express fibromodulin. Activation (phorbol 12
      myristate 13-acetate [PMA]/ionomycin) of normal T and B lymphocytes induced weak
      fibromodulin gene expression, but not to the extent seen in freshly isolated B
      CLL cells. The reason for the exclusive ectopic expression of fibromodulin in B
      CLL and MCL is unknown. However, its unique protein expression makes it likely
      that fibromodulin is involved in the pathobiology of B-CLL and MCL.

PMID- 15741215
TI  - A single amino acid change, A91V, leads to conformational changes that can impair
      processing to the active form of perforin.
AB  - Mutations in the perforin gene have been found in patients with hemophagocytic
      lymphohistiocytosis (HLH), a rare autosomal recessive disease. We describe a
      patient expressing perforin with amino acid changes A91V and W374X. The ability
      of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to lyse target
      cells is greatly reduced. Here we demonstrate that perforin from this patient is
      not recognized using an antibody raised against native perforin (deltaG9), but is
      readily detected using an antibody raised against a peptide epitope (2d4),
      suggesting that the epitope recognized by deltaG9 is destroyed by the change at
      A91V. Immunoblotting reveals no protein corresponding to the truncated transcript
      encoded by W374X, revealing that only perforin with the A91V change is expressed
      in CTLs from the patient. Patient CTLs show bands corresponding to the immature
      and intermediate forms of perforin, but the mature active form of perforin is
      absent or barely detectable. The conformational changes and impaired cleavage of
      A91V perforin are likely to explain the reduced cytotoxicity in CTLs and NK cells
      from this patient and are likely to contribute to the pathogenesis of HLH.

PMID- 15741216
TI  - Low Mpl receptor expression in a pedigree with familial platelet disorder with
      predisposition to acute myelogenous leukemia and a novel AML1 mutation.
AB  - Germ-line heterozygous mutations in the hematopoietic transcription factor AML1
      (RUNX1) have been identified in patients with familial platelet disorder with
      predisposition to acute myelogenous leukemia (FPD/AML), which is characterized by
      thrombocytopenia, abnormal platelet function, and propensity to myeloid
      malignancies. We identified a novel mutation in the AML1 gene in an FPD/AML
      pedigree characterized by a single nucleotide deletion that generates a
      frameshift and premature chain termination (Pro218fs-Ter225). Both wild-type and
      mutant transcripts were expressed in affected individuals by allele-specific
      reverse transcriptase-polymerase chain reaction (RT-PCR). Thrombopoietin (TPO)
      binds to the Mpl receptor and is the major regulator of megakaryopoiesis. To
      explore the mechanisms underlying thrombocytopenia, we studied the TPO/Mpl
      pathway in this newly identified pedigree. TPO levels were mildly to moderately
      elevated. On flow cytometry and immunoblotting, Mpl receptor expression was
      decreased and TPO-induced signaling was impaired. While no mutations were
      identified in the MPL gene by sequence analysis, low MPL mRNA levels were found,
      suggesting decreased gene expression. Of particular interest, several AML1
      binding motifs are present in the MPL promoter, suggesting MPL is an AML1 target.
      In conclusion, we identified a C-terminal AML1 mutation that leads to a decrease
      in Mpl receptor expression, providing a potential explanation for
      thrombocytopenia in this FPD/AML pedigree.

PMID- 15741217
TI  - Phenotypic characterization of the human myeloma cell growth fraction.
AB  - In this study we quantified the proliferation rate of normal and malignant plasma
      cells (PCs) by ex vivo incorporation of 5-bromo-2'-deoxyuridine (BrdU; labeling
      index, LI) using flow cytometry. We show that all bone marrow PCs, either normal
      or malignant, include a subset of proliferating PCs present within the
      CD45(bright) fraction. Indeed, medullary normal and malignant PCs were always
      heterogeneous for CD45 expression, and proliferation was always restricted
      primarily to the CD45(bright) compartment. Moreover, an inverse correlation was
      found between LI or CD45 and B-cell lymphoma 2 (Bcl-2) in both malignant and
      normal PCs, the most proliferating CD45(bright) PCs have the lowest Bcl-2
      expression. We investigated expression of molecules of interest in multiple
      myeloma (MM)-that is, CD138, CD19, CD20, CD27, CD28, CD56, and CD11a-to further
      characterize the CD45(bright) fraction. Among all of these molecules, only CD11a
      was exclusively expressed by CD45(bright) proliferating myeloma cells. In
      conclusion, proliferating myeloma cells are characterized by the specific
      CD45(bright) CD11a(pos) Bcl-2(low) phenotype.

PMID- 15741218
TI  - Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by
      desensitizing S1P receptors.
AB  - Mast cells play a central role in inflammatory and immediate-type allergic
      reactions by secreting a variety of biologically active substances, including
      sphingosine-1 phosphate (S1P). Sphingosine kinase 1 (SphK1) and formation of S1P,
      which leads to transactivation of S1P receptors and their downstream signaling
      pathways, regulates mast-cell functions initiated by cross-linking of the high
      affinity immunoglobulin E (IgE) receptor FcepsilonRI. Surprisingly,
      overexpression of SphK1 in rat basophilic leukemia (RBL)-2H3 mast cells impaired
      degranulation as well as migration toward antigen. These effects were reversed by
      serum withdrawal, yet the increased formation and secretion of S1P were the same
      as in the presence of serum. Nonetheless, serum increased localization of SphK1
      at the plasma membrane. This restricted formation of S1P induced internalization
      and desensitization of S1P receptors on the surface of mast cells as determined
      by confocal immunofluorescence microscopy, aberrant S1P receptor signaling, and
      lack of S1P receptor coupling to G proteins. Serum starvation, which
      significantly reduced membrane-associated SphK1 activity, restored S1P receptor
      functions. Our results have important implications for mast-cell migration and
      degranulation as well as for the biologic functions of the S1P receptors on cells
      that are circulating in the bloodstream.

PMID- 15741219
TI  - Telomere loss, senescence, and genetic instability in CD4+ T lymphocytes
      overexpressing hTERT.
AB  - Little is known about the long-term consequences of overexpression of the human
      telomerase reverse transcriptase (hTERT) gene in T lymphocytes. To address this
      issue, we transduced polyclonal as well as clonally derived populations of naive
      and memory CD44 T cells from 2 healthy donors (aged 24 and 34 years) with
      retroviral vectors encoding green fluorescence protein (GFP) and hTERT (GFP
      hTERT) or GFP alone. After transduction, cells were sorted on the basis of GFP
      expression and cultured in vitro until senescence. T cells transduced with hTERT
      exhibited high stable telomerase activity throughout the culture period. Relative
      to GFP controls, minor changes in overall gene expression were observed yet the
      proliferative lifespan of the hTERT-transduced populations was significantly
      increased and the rate of telomere loss was lower. Nevertheless, hTERT-transduced
      cells showed progressive telomere loss and had shorter telomeres at senescence
      than controls (2.3 +/- 0.3 kilobase [kb] versus 3.4 +/- 0.1 kb). Furthermore, a
      population of cells with 4N DNA consisting of binucleated cells with connected
      nuclei emerged in the hTERT-transduced cells prior to senescence. We conclude
      that overexpression of hTERT in CD4+ T cells provides a proliferative advantage
      independent of the average telomere length but does not prevent eventual genetic
      instability and replicative senescence.

PMID- 15741221
TI  - Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with
      activated platelets to initiate coagulation.
AB  - Tissue factor (TF) circulates in plasma, largely on monocyte/macrophage-derived
      microvesicles that can bind activated platelets through a mechanism involving P
      selectin glycoprotein ligand-1 (PSGL-1) on the microvesicles and P-selectin on
      the platelets. We found these microvesicles to be selectively enriched in both TF
      and PSGL-1, and deficient in CD45, suggesting that they arise from distinct
      membrane microdomains. We investigated the possibility that microvesicles arise
      from cholesterol-rich lipid rafts and found that both TF and PSGL-1, but not
      CD45, localize to lipid rafts in blood monocytes and in the monocytic cell line
      THP-1. Consistent with a raft origin of TF-bearing microvesicles, their shedding
      was significantly reduced with depletion of membrane cholesterol. We also
      evaluated the interaction between TF-bearing microvesicles and platelets.
      Microvesicles bound only activated platelets, and required PSGL-1 to do so. The
      microvesicles not only bound the activated platelets, they fused with them,
      transferring both proteins and lipid to the platelet membrane. Fusion was blocked
      by either annexin V or an antibody to PSGL-1 and had an important functional
      consequence: increasing the proteolytic activity of the TF-VIIa complex. These
      findings suggest a mechanism by which all of the membrane-bound reactions of the
      coagulation system can be localized to the surface of activated platelets.

PMID- 15741220
TI  - Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for
      ceruloplasmin regulation.
AB  - Cellular oxygen partial pressure is sensed by a family of prolyl-4-hydroxylase
      domain (PHD) enzymes that modify hypoxia-inducible factor (HIF)alpha subunits.
      Upon hydroxylation under normoxic conditions, HIFalpha is bound by the von Hippel
      Lindau tumor suppressor protein and targeted for proteasomal destruction. Since
      PHD activity is dependent on oxygen and ferrous iron, HIF-1 mediates not only
      oxygen- but also iron-regulated transcriptional gene expression. Here we show
      that copper (CuCl(2)) stabilizes nuclear HIF-1alpha under normoxic conditions,
      resulting in hypoxia-response element (HRE)-dependent reporter gene expression.
      In in vitro hydroxylation assays CuCl(2) inhibited prolyl-4-hydroxylation
      independently of the iron concentration. Ceruloplasmin, the main copper transport
      protein in the plasma and a known HIF-1 target in vitro, was also induced in vivo
      in the liver of hypoxic mice. Both hypoxia and CuCl(2) increased ceruloplasmin
      (as well as vascular endothelial growth factor [VEGF] and glucose transporter 1
      [Glut-1]) mRNA levels in hepatoma cells, which was due to transcriptional
      induction of the ceruloplasmin gene (CP) promoter. In conclusion, our data
      suggest that PHD/HIF/HRE-dependent gene regulation can serve as a sensory system
      not only for oxygen and iron but also for copper metabolism, regulating the
      oxygen-, iron- and copper-binding transport proteins hemoglobin, transferrin, and
      ceruloplasmin, respectively.

PMID- 15741222
TI  - Thalidomide-induced antiangiogenic action is mediated by ceramide through
      depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate.
AB  - Thalidomide, which is clinically recognized as an efficient therapeutic agent for
      multiple myeloma, has been thought to exert antiangiogenic action through an
      unknown mechanism. We here show a novel mechanism of thalidomide-induced
      antiangiogenesis in zebrafish embryos. Thalidomide induces the defect of major
      blood vessels, which is demonstrated by their morphologic loss and confirmed by
      the depletion of vascular endothelial growth factor (VEGF) receptors such as
      neuropilin-1 and Flk-1. Transient increase of ceramide content through activation
      of neutral sphingomyelinase (nSMase) precedes thalidomide-induced vascular defect
      in the embryos. Synthetic cell permeable ceramide, N-acetylsphingosine (C2
      ceramide) inhibits embryonic angiogenesis as well as thalidomide. The blockade of
      ceramide generation by antisense morpholino oligonucleotides for nSMase prevents
      thalidomide-induced ceramide generation and vascular defect. In contrast to
      ceramide, sphingosine-1-phosphate (S1P) inhibits nSMase-dependent ceramide
      generation and restores thalidomide-induced embryonic vascular defect with an
      increase of expression of VEGF receptors. In human umbilical vein endothelial
      cells (HUVECs), thalidomide-induced inhibition of cell growth, generation of
      ceramide through nSMase, and depletion of VEGF receptors are restored to the
      control levels by pretreatment with S1P. These results suggest that thalidomide
      induced antiangiogenic action is regulated by the balance between ceramide and
      S1P signal.

PMID- 15741223
TI  - Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic
      cells but maintains their Th2 priming potential.
AB  - Interleukin-4 (IL-4), a major T-helper type 2 (Th2) cytokine, primes dendritic
      cells (DCs) for IL-12 production, suggesting a negative feedback loop to prevent
      dysregulated Th2 inflammation, such as allergy. We previously showed that human
      thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes of atopic
      dermatitis, activates CD11c(+) DCs to induce the differentiation of naive CD4(+)
      and CD8(+) T cells into proallergic effectors. Here we show that TSLP primes DCs
      to produce large amounts of IL-12 after CD40 ligand stimulation, similar to IL-4
      priming of DCs. In contrast to IL-4 priming, DCs activated with TSLP and CD40
      ligand induce the differentiation of naive CD4(+) T cells into effectors
      producing both Th1 and Th2 cytokines, a unique profile that is reminiscent of the
      late phase of allergy. Thus, TSLP is a major regulatory cytokine for IL-12
      production by DCs, and TSLP-activated DCs could promote the persistence of Th2
      inflammation even in the presence of IL-12-inducing signals.

PMID- 15741224
TI  - Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma
      with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and
      interferon alpha.
AB  - Treatment-related myelodysplasia (t-MDS) occurs less frequently with the
      nucleoside analogs than with DNA-damaging agents such as alkylators or
      topoisomerase II inhibitors. In a chemoimmunotherapy trial conducted between 1997
      and 2003 in patients with stage IV indolent lymphoma, 202 patients were treated
      and 8 have developed MDS between 1 and 5 years after therapy, including 4 who
      received only fludarabine, mitoxantrone, and dexamethasone (FND) for 6 to 8
      courses, with or without rituximab, followed by interferon alpha (IFN-alpha).
      Complex cytogenetic abnormalities were present in all patients. Abnormalities of
      chromosome 7 were present in 6 of the 8 patients, 3 of whom received only FND +/-
      rituximab and IFN-alpha. The abnormalities of chromosome 7 were monosomy 7 in 4
      patients (1 of which had add 7p in the remaining chromosome); 1 del 7q; and 1 der
      7. MDS with features classically associated with DNA-damaging agents can occur
      following therapy with FND, with or without rituximab, and IFN-alpha.

PMID- 15741225
TI  - Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non
      small-cell lung cancer: a phase III study addressing the case for cisplatin.
AB  - BACKGROUND: This multicenter, randomized, phase III study compared the efficacy,
      including progression-free survival (PFS), and safety of gemcitabine-docetaxel
      (GD) combination versus cisplatin-vinorelbine (CV) in the treatment of advanced
      non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients
      with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m(2) days 1
      and 8 plus docetaxel 85 mg/m(2) day 8, every 3 weeks for eight cycles) or CV
      (cisplatin 100 mg/m(2) day 1 plus vinorelbine 30 mg/m(2), days 1, 8, 15 and 22,
      every 4 weeks for six cycles). RESULTS: A total of 311 patients were enrolled
      (155 GD and 156 CV). Neither PFS nor overall survival differed significantly
      between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6
      months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm
      compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence
      interval (CI) 0.83-1.32], and for overall survival, it was 0.90 (95% CI 0.70
      1.16). Objective response rates did not differ significantly (31% for GD, 35.9%
      for CV). Myelosupression, emesis and frequency of febrile neutropenia were less
      pronounced on the GD arm, whereas fluid retention and pulmonary events were more
      pronounced. The CV arm experienced a higher number of serious adverse events and
      a lower compliance with the protocol. There was no quality of life (QoL)
      difference between arms. Median time to definite impairment of health-related QoL
      was 153 and 168 days in GD and CV arms, respectively. CONCLUSIONS: There was no
      advantage in PFS with GD compared with CV; however, the CV regimen had higher
      rate of toxic events, mainly myelosuppression. The herein, non-platinum
      containing regimen could be considered as a rational alternative to the cisplatin
      based doublet.

PMID- 15741226
TI  - Interferon-alpha as maintenance therapy in patients with multiple myeloma.
AB  - BACKGROUND: The effect of interferon-alpha 2b (IFN-alpha-2b) on progression-free
      and overall survival as well as quality of life (QoL) was studied in mainly
      elderly patients with multiple myeloma (MM), who reached a plateau phase after
      melphalan/prednisone induction. PATIENTS AND METHODS: In an open phase III trial,
      262 patients, median age 69 years (range 34-91), received at least 10 monthly
      courses of melphalan/prednisone followed by response evaluation. Plateau phase
      was reached by 128 patients. Next, 90 patients were randomized between IFN-alpha
      2b and no maintenance therapy. Reasons for non-randomization were: refusal (18),
      concomitant disease (nine), protocol violation (six), WHO performance status >2
      (four) and allogeneic transplantation (one) RESULTS: At a median follow-up from
      diagnosis of 97 months (0-140) for those patients alive, IFN-alpha-2b therapy was
      associated with improved progression-free survival (median 13.5 versus 8.4 months
      from randomization), although this did not translate in a better overall survival
      (41 versus 38.4 months). One-third of patients discontinued IFN-alpha due to
      toxicity. No differences were observed between patient groups in QoL.
      CONCLUSIONS: IFN maintenance therapy in MM prolongs progression-free survival
      and, provided that the burden of toxicity is not too high, does not adversely
      affect QoL.

PMID- 15741227
TI  - Impact of the elevation of biochemical markers of myocardial damage on long-term
      mortality after percutaneous coronary intervention: results of the CK-MB and PCI
      study.
AB  - AIMS: Retrospective studies and post hoc analyses have suggested that mild
      elevations in the creatine kinase-MB (CK-MB) isoenzyme following percutaneous
      coronary intervention (PCI) may be associated with an increased risk of death in
      the long term. However, this finding is still controversial, and the prognostic
      significance of elevations of more sensitive markers of myocardial damage, such
      as the cardiac troponins, has not been established. In this multicentre
      prospective cohort study, we evaluated the influence of post-procedural
      elevations of CK-MB and troponin I (cTnI) on long-term mortality. METHODS AND
      RESULTS: The CK-MB and PCI study included 3494 consecutive patients undergoing
      PCI from February 2000 to October 2000 in 16 Italian tertiary centres. Blood
      samples were collected at baseline, and at 8-12 and 18-24 h after the procedure,
      and were analysed in a core biochemistry laboratory. CK-MB elevation was detected
      in 16% of the patients, and was associated with increased 2-year mortality [7.2
      vs. 3.8%; odds ratio (OR): 1.9; 95% confidence interval (CI): 1.3-2.8; P<0.001).
      The degree of CK-MB elevation (peak CK-MB ratio) independently predicted the risk
      of death (adjusted OR per unit: 1.04; 95% CI: 1.01-1.07; P=0.009). A cTnI
      elevation was detected in 44.2% of the cases and was not associated with a
      significant increase in mortality (4.9 vs. 4.0%; OR: 1.2; 95% CI: 0.9-1.7;
      P=0.2). CONCLUSION: Post-procedural elevations of CK-MB, but not cTnI, influence
      2-year mortality.

PMID- 15741228
TI  - Reduction of fluoroscopy exposure and procedure duration during ablation of
      atrial fibrillation using a novel anatomical navigation system.
AB  - AIMS: Catheter ablation of atrial fibrillation (AF) is centred on pulmonary vein
      (PV) ablation with or without additional atrial substrate modification. These
      procedures may be prolonged with significant fluoroscopy exposure. This study
      evaluates a new non-fluoroscopic navigation system during ablation of AF. METHODS
      AND RESULTS: Seventy-two patients undergoing catheter ablation of symptomatic
      drug refractory AF were prospectively randomized to ablation with (n=35; study
      group) or without (n=37; control group) non-fluoroscopic navigation. PV isolation
      was performed in all patients. In patients with persistent or inducible sustained
      AF after PV isolation linear ablation was performed by joining the superior PVs.
      PV isolation was achieved in all patients; fluoroscopy (15.4+/-3.4 vs. 21.3+/-6.4
      min; P<0.001) and procedural (52+/-12 vs. 61+/-17 min; P=0.02) durations were
      significantly reduced in the study group. Linear block was achieved in 37 of the
      39 patients; with a significant reduction in fluoroscopy (5.6+/-2.2 vs. 9.9+/-4.8
      min; P=0.003) and procedural (14.7+/-5.5 vs. 26.6+/-16.9 min; P=0.007) durations
      in the study group. After a follow-up of 6.9+/-2.9 months (range 3-10), 26 (74%)
      patients in the non-fluoroscopic navigation group and 29 (78%) patients in the
      control group were arrhythmia-free after the first procedure. CONCLUSION: This
      prospectively randomized study demonstrates significant reduction of fluoroscopy
      exposure and procedural duration using supplementary non-fluoroscopic imaging
      system for AF ablation.

PMID- 15741229
TI  - Stimulation of erythrocyte ceramide formation by platelet-activating factor.
AB  - Osmotic erythrocyte shrinkage leads to activation of cation channels with
      subsequent Ca2+ entry and stimulates a sphingomyelinase with subsequent formation
      of ceramide. Ca2+ and ceramide then activate a scramblase leading to breakdown of
      phosphatidylserine asymmetry of the cell membrane. The mediators accounting for
      activation of erythrocyte sphingomyelinase and phosphatidylserine exposure
      remained elusive. The study demonstrates that platelet-activating factor (PAF) is
      released from erythrocytes upon hyperosmotic cell shrinkage. The experiments
      further disclose the presence of PAF receptors in erythrocytes and show that PAF
      stimulates the breakdown of sphingomyelin and the release of ceramide from
      erythrocytes at isotonic conditions. PAF further triggers cell shrinkage
      (decrease of forward scatter) and phosphatidylserine exposure (annexin binding)
      of erythrocytes. The stimulation of annexin-binding is blunted by a genetic
      knockout of PAF receptors, by the PAF receptor antagonist ABT491 or by inhibition
      of sphingomyelinase with urea. In conclusion, PAF activates an erythrocyte
      sphingomyelinase and the then formed ceramide leads to the activation of
      scramblase with subsequent phosphatidylserine exposure.

PMID- 15741230
TI  - Signal recognition particle assembly in relation to the function of amplified
      nucleoli of Xenopus oocytes.
AB  - The signal recognition particle (SRP) is a ribonucleoprotein machine that
      controls the translation and intracellular sorting of membrane and secreted
      proteins. The SRP contains a core RNA subunit with which six proteins are
      assembled. Recent work in both yeast and mammalian cells has identified the
      nucleolus as a possible initial site of SRP assembly. In the present study, SRP
      RNA and protein components were identified in the extrachromosomal, amplified
      nucleoli of Xenopus laevis oocytes. Fluorescent SRP RNA microinjected into the
      oocyte nucleus became specifically localized in the nucleoli, and endogenous SRP
      RNA was also detected in oocyte nucleoli by RNA in situ hybridization. An initial
      step in the assembly of SRP involves the binding of the SRP19 protein to SRP RNA.
      When green fluorescent protein (GFP)-tagged SRP19 protein was injected into the
      oocyte cytoplasm it was imported into the nucleus and became concentrated in the
      amplified nucleoli. After visiting the amplified nucleoli, GFP-tagged SRP19
      protein was detected in the cytoplasm in a ribonucleoprotein complex, having a
      sedimentation coefficient characteristic of the SRP. These results suggest that
      the amplified nucleoli of Xenopus oocytes produce maternal stores not only of
      ribosomes, the classical product of nucleoli, but also of SRP, presumably as a
      global developmental strategy for stockpiling translational machinery for early
      embryogenesis.

PMID- 15741231
TI  - Intracellular fate of LDL receptor family members depends on the cooperation
      between their ligand-binding and EGF domains.
AB  - The insect low-density lipoprotein (LDL) receptor (LDLR) homologue LpR mediates
      endocytosis of an insect lipoprotein (lipophorin) that is structurally related to
      LDL. Despite these similarities, lipophorin and LDL follow distinct intracellular
      routes upon endocytosis by their receptors. Whereas LDL is degraded in lysosomes,
      lipophorin is recycled in a transferrin-like manner. We constructed several
      hybrid receptors composed of Locusta migratoria LpR and human LDLR regions to
      identify the domains implicated in LpR-mediated ligand recycling. Additionally,
      the triadic His562 residue of LDLR, which is putatively involved in ligand
      uncoupling, was mutated to Asn, corresponding to Asn643 in LpR, to analyse the
      role of the His triad in receptor functioning. The familial hypercholesterolaemia
      (FH) class 5 mutants LDLR(H562Y) and LDLR(H190Y) were also analysed in vitro.
      Fluorescence microscopic investigation and quantification suggest that LpR
      mediated ligand recycling involves cooperation between the ligand-binding domain
      and epidermal growth factor (EGF) domain of LpR, whereas its cytosolic tail does
      not harbour motifs that affect this process. LDLR residue His562 appears to be
      essential for LDLR recycling after ligand endocytosis but not for constitutive
      receptor recycling. Like LDLR(H562N), LDLR(H562Y) did not recycle bound ligand;
      moreover, the intracellular distribution of both mutant receptors after ligand
      incubation coincides with that of a lysosomal marker. The LDLR mutant
      characterization in vitro suggests that LDLR FH class 5 mutations might be
      divided into two subclasses.

PMID- 15741232
TI  - p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal
      cell death.
AB  - In large models of neuronal cell death, there is a tight correlation between Cdk5
      deregulation and cell-cycle dysfunction. However, pathways that link Cdk5 to the
      cell cycle during neuronal death are still unclear. We have investigated the
      molecular events that precede p25/Cdk5-triggered neuronal death using a neuronal
      cell line that allows inducible p25 expression. In this system, no sign of
      apoptosis was seen before 24 hours of p25 induction. Thus, at that time, cell
      cycle-regulatory proteins were analysed by immunoblotting and some of them showed
      a significant deregulation. Interestingly, after time-course experiments, the
      earliest feature correlated with p25 expression was the phosphorylation of the
      retinoblastoma protein (Rb). Indeed, this phosphorylation was observed 6 hours
      after p25 induction and was abolished in the presence of a Cdk5 inhibitor,
      roscovitine, which does not inhibit the usual Rb cyclin-D kinases Cdk4 and Cdk6.
      Furthermore, analyses of levels and subcellular localization of Cdk-related
      cyclins did not reveal any change following Cdk5 activation, arguing for a direct
      effect of Cdk5 activity on Rb protein. This latter result was clearly
      demonstrated by in vitro kinase assays showing that the p25-Cdk5 complex in our
      cell system phosphorylates Rb directly without the need for any intermediary
      kinase activity. Hence, Rb might be an appropriate candidate that connects Cdk5
      to cell-cycle deregulation during neuronal cell death.

PMID- 15741233
TI  - A dynamin-3 spliced variant modulates the actin/cortactin-dependent morphogenesis
      of dendritic spines.
AB  - Immature dendrites extend many actin-rich filopodial structures that can be
      replaced by synapse-containing dendritic spines as the neuron matures. The large
      GTPase dynamin-3 (Dyn3) is a component of the postsynapse in hippocampal neurons
      but its function is undefined. Here, we demonstrate that a specific Dyn3 variant
      (Dyn3baa) promotes the formation of immature dendritic filopodia in cultured
      neurons. This effect is dependent upon Dyn3 GTPase activity and a direct
      interaction with the F-actin-binding protein cortactin. Consistent with these
      findings, Dyn3baa binds to cortactin with a 200% higher affinity than Dyn3aaa, a
      near identical isoform that does not induce dendritic filopodia when expressed in
      cultured neurons. Finally, levels of Dyn3baa-encoding mRNA are tightly regulated
      during neuronal maturation and are markedly upregulated during synaptogenesis.
      Together, these findings provide the first evidence that an enhanced interaction
      between a specific Dyn3 splice variant and cortactin modulate actin-membrane
      dynamics in developing neurons to regulate the morphogenesis of dendritic spines.

PMID- 15741235
TI  - The neurogene BTG2TIS21/PC3 is transactivated by DeltaNp73alpha via p53
      specifically in neuroblastoma cells.
AB  - The p53 gene and its homologue p73 are rarely mutated in neuroblastoma. In recent
      studies, we showed that overexpression of DeltaNp73alpha, an isoform lacking the
      N-terminal transactivation (TA) domain, surprisingly induces p53 protein
      accumulation in the wild-type (wt) p53 human neuroblastoma line SH-SY5Y. As can
      be expected owing to its dominant-negative effect, DeltaNp73alpha inhibits
      Waf1/p21 gene expression, but equally importantly, it upregulates BTG2TIS21/PC3,
      another p53 target gene. This effect is not observed in neuroblastoma cells that
      express a mutated p53. To better understand the DeltaNp73-mediated
      transactivation of the BTG2TIS21/PC3 gene we performed luciferase assays with two
      reporter plasmids harboring long and short BTG2 promoter sequences in three human
      neuroblastoma cell lines and one breast cancer cell line. Our results demonstrate
      that BTG2TIS21/PC3 transactivation by DeltaNp73alpha depends on both p53 status
      (as it is not observed in a p53-/- neuroblastoma cell line) and cellular context
      (as it occurs in a p53+/+ neuroblastoma cell line but not in a p53+/+ breast
      tumor cell line). The fact that DeltaNp73alpha may either inhibit or stimulate wt
      p53 transcriptional activity, depending on both the p53 target gene and the
      cellular context, was confirmed by real-time quantitative PCR. Moreover,
      transactivation of the BTG2TIS21/PC3 promoter requires a complete DeltaNp73alpha
      C-terminus sequence as it is not observed with DeltaNp73beta, which lacks most of
      the C-terminal domain. We have previously shown that DeltaNp73alpha is the only
      p73 isoform expressed in undifferentiated neuroblastoma tumors. In light of all
      these findings, we propose that DeltaNp73alpha not only acts as an inhibitor of
      p53/TAp73 functions in neuroblastoma tumors, but also cooperates with wt-p53 in
      playing a physiological role through the activation of BTG2TIS21/PC3 gene
      expression.

PMID- 15741234
TI  - Higher-order nuclear organization in growth arrest of human mammary epithelial
      cells: a novel role for telomere-associated protein TIN2.
AB  - Nuclear organization, such as the formation of specific nuclear subdomains, is
      generally thought to be involved in the control of cellular phenotype; however,
      there are relatively few specific examples of how mammalian nuclei organize
      during radical changes in phenotype, such as those occurring during
      differentiation and growth arrest. Using human mammary epithelial cells in which
      growth arrest is essential for morphological differentiation, we show that the
      arrest of cell proliferation is accompanied by a reorganization of the telomere
      associated protein, TIN2, into one to three large nuclear subdomains. The large
      TIN2 domains do not contain telomeres and occur concomitant with the continued
      presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNase, but not
      RNase, occurred frequently, but not exclusively near nucleoli, and overlapped
      often with dense domains containing heterochromatin protein 1gamma. Expression of
      truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains
      and relaxed the stringent morphogenesis-induced growth arrest in human mammary
      epithelial cells. Here we show that a novel extra-telomeric organization of TIN2
      is associated with the control of cell proliferation and identify TIN2 as an
      important regulator of mammary epithelial differentiation.

PMID- 15741236
TI  - Actin-filament cross-linking protein T-plastin increases Arp2/3-mediated actin
      based movement.
AB  - Increasing evidence suggests that actin cross-linking or bundling proteins might
      not only structure the cortical actin cytoskeleton but also control actin
      dynamics. Here, we analyse the effects of T-plastin/T-fimbrin, a representative
      member of an important actin-filament cross-linking protein by combining a
      quantitative biomimetic motility assay with biochemical and cell-based
      approaches. Beads coated with the VCA domain of the Wiskott/Aldrich-syndrome
      protein (WASP) recruit the actin-nucleating Arp2/3 complex, polymerize actin at
      their surface and undergo movement when placed in cell-free extracts. T-Plastin
      increased the velocity of VCA beads 1.5 times, stabilized actin comets and
      concomitantly displaced cofilin, an actin-depolymerizing protein. T-Plastin also
      decreased the F-actin disassembly rate and inhibited cofilin-mediated
      depolymerization of actin filaments in vitro. Importantly, a bundling-incompetent
      variant comprising the first actin-binding domain (ABD1) had similar effects. In
      cells, this domain induced the formation of long actin cables to which other
      actin-regulating proteins were recruited. Altogether, these results favor a
      mechanism in which binding of ABD1 controls actin turnover independently of cross
      link formation. In vivo, this activity might contribute to the assembly and
      maintenance of the actin cytoskeleton of plasma-membrane protrusions.

PMID- 15741237
TI  - Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin
      like cell-cell adhesion molecule localizing at non-junctional contact sites of
      presynaptic nerve terminals, axons and glia cell processes.
AB  - Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and
      comprise a family of four members. At the mossy fiber terminals of hippocampus,
      nectin-1 and nectin-3 localize at the presynaptic and postsynaptic sides of
      synaptic junctions, respectively, and their trans-interactions play a role in
      formation of synapses in cooperation with N-cadherin. Nectins are associated with
      the actin cytoskeleton through afadin, a nectin- and actin-filament-binding
      protein. Five nectin-like molecules (Necls) which have domain structures similar
      to those of nectins have been identified and here we characterize Necl
      1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis
      showed that Necl-1 was specifically expressed in the neural tissue.
      Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized
      at the contact sites among axons, their terminals, and glia cell processes that
      cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed
      Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed
      Ca2+-independent heterophilic cell-cell adhesion activity with Necl
      2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, nectin-1
      and nectin-3, but not with Necl-5 or nectin-2. The C-terminal cytoplasmic region
      of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase
      subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK.
      These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent
      immunoglobulin-like cell-cell adhesion molecule which potentially has membrane
      associated guanylate kinase subfamily member-binding activity and localizes at
      the non-junctional cell-cell contact sites.

PMID- 15741238
TI  - Repeated light-dark shifts speed up body weight gain in male F344 rats.
AB  - This study is aimed at verifying the causal relationship of chronic circadian
      desynchronization and changes in body weight control. Eight male albino F344 rats
      aged between 12-15 wk were subjected to twice weekly 12-h shifts of the daily
      light-dark (LD) cycle for 13 wk (3 mo). Continuous circadian phase shifts
      consisting of intermittent phase delay and advance and reduced circadian
      amplitudes were consistently displayed in all five experimental rats implanted
      intraperitoneally with heart rate, body temperature, and activity transponders.
      The experimental rat maintained a greater body weight during LD shifts and even
      after 10 days of recovery than that of the age-matched control rat, which was
      maintained on a regular LD cycle. Body weight gain was greater in the first 2 mo
      of LD shifts in the experimental rat than in the control rat. Relative to the
      baseline, food intake and activity percentages were increased and reduced,
      respectively, for the experimental rats. Features of these results, such as
      increased body weight gain and food intake, and reduced activity, suggest a
      causal relationship of chronic circadian desynchronization and changes in body
      weight control in male albino F344 rats.

PMID- 15741239
TI  - Regulation of leptin secretion from white adipocytes by insulin, glycolytic
      substrates, and amino acids.
AB  - The aim of the present study was to determine the respective roles of energy
      substrates and insulin on leptin secretion from white adipocytes. Cells secreted
      leptin in the absence of glucose or other substrates, and addition of glucose (5
      mM) increased this secretion. Insulin doubled leptin secretion in the presence of
      glucose (5 mM), but not in its absence. High concentrations of glucose (up to 25
      mM) did not significantly enhance leptin secretion over that elicited by 5 mM
      glucose. Similar results were obtained when glucose was replaced by pyruvate or
      fructose (both 5 mM). L-Glycine or L-alanine mimicked the effect of glucose on
      basal leptin secretion but completely prevented stimulation by insulin. On the
      other hand, insulin stimulated leptin secretion when glucose was replaced by L
      aspartate, L-valine, L-methionine, or L-phenylalanine, but not by L-leucine (all
      5 mM). Interestingly, these five amino acids potently increased basal and insulin
      stimulated leptin secretion in the presence of glucose. Unexpectedly, L-glutamate
      acutely stimulated leptin secretion in the absence of glucose or insulin.
      Finally, nonmetabolizable analogs of glucose or amino acids were without effects
      on leptin secretion. These results suggest that 1) energy substrates are
      necessary to maintain basal leptin secretion constant, 2) high availability of
      glycolysis substrates is not sufficient to enhance leptin secretion but is
      necessary for its stimulation by insulin, 3) amino acid precursors of
      tricarboxylic acid cycle intermediates potently stimulate basal leptin secretion
      per se, with insulin having an additive effect, and 4) substrates need to be
      metabolized to increase leptin secretion.

PMID- 15741240
TI  - Contraction activates glucose uptake and glycogen synthase normally in muscles
      from dexamethasone-treated rats.
AB  - Glucocorticoids cause insulin resistance in skeletal muscle. The aims of the
      present study were to investigate the effects of contraction on glucose uptake,
      insulin signaling, and regulation of glycogen synthesis in skeletal muscles from
      rats treated with the glucocorticoid analog dexamethasone (1 mg x kg(-1) x day(
      1) ip for 12 days). Insulin resistance in dexamethasone-treated rats was
      confirmed by reduced insulin-stimulated glucose uptake (approximately 35%),
      glycogen synthesis (approximately 70%), glycogen synthase activation
      (approximately 80%), and PKB Ser(473) phosphorylation (approximately 40%).
      Chronic dexamethasone treatment did not impair glucose uptake during contraction
      in soleus or epitrochlearis muscles. In epitrochlearis (but not in soleus), the
      presence of insulin during contraction enhanced glucose uptake to similar levels
      in control and dexamethasone-treated rats. Contraction also increased glycogen
      synthase fractional activity and dephosphorylated glycogen synthase at Ser(645),
      Ser(649), Ser(653), and Ser(657) normally in muscles from dexamethasone-treated
      rats. After contraction, insulin-stimulated glycogen synthesis was completely
      restored in epitrochlearis and improved in soleus from dexamethasone-treated
      rats. Contraction did not increase insulin-stimulated PKB Ser(473) or glycogen
      synthase kinase-3 (GSK-3) phosphorylation. Instead, contraction increased GSK
      3beta Ser(9) phosphorylation in epitrochlearis (but not in soleus) in muscles
      from control and dexamethasone-treated rats. In conclusion, contraction
      stimulates glucose uptake normally in dexamethasone-induced insulin resistant
      muscles. After contraction, insulin's ability to stimulate glycogen synthesis was
      completely restored in epitrochlearis and improved in soleus from dexamethasone
      treated rats.

PMID- 15741241
TI  - Regulation by glucagon of the rat histidase gene promoter in cultured rat
      hepatocytes and human hepatoblastoma cells.
AB  - Histidase (Hal), the amino acid-degrading enzyme of histidine, is regulated by
      the protein content of the diet and by hormones such as glucocorticoids and
      glucagon. However, glucagon can activate the following two possible transduction
      pathways: protein kinase A (PKA) and protein kinase C (PKC). The aim of this
      study was to isolate the 5'-flanking region of rat Hal gene to locate possible
      cAMP- and glucocorticoid-responsive elements and to identify whether the
      activation of the Hal promoter by glucagon occurs via PKA or PKC. The results
      showed that glucagon was able to induce Hal expression 1.5-fold in primary
      hepatocytes. The addition of phorbol 12-myristate,13-acetate (PMA) and forskolin
      to hepatocytes increased Hal mRNA concentration by 100 and 40%, respectively. To
      identify the Hal gene regulatory region, a 1248-bp fragment of the 5'-region was
      obtained. The transcription initiation site was located at 404 bp from ATG. The
      sequence did not show consensus TATA-like or CAAT-like boxes in the first 100 bp
      upstream from the transcription start site. The promoter contained six GC rich
      boxes, seven putative AP1 binding sites, and four glucocorticoid-responsive
      elements. The putative Hal promoter region was cloned into the pGL3basic vector
      and transfected into HepG2 cells. Luciferase expression was significantly
      stimulated by glucagon (0.9-fold), forskolin (0.9-fold), PMA (2.0-fold), and
      dexamethasone (2.9-fold). This evidence supports that the Hal gene is turned on
      by glucocorticoids and by glucagon either via PKC or PKA, but prefers the PKA
      pathway.

PMID- 15741242
TI  - Characterization of big stanniocalcin variants in mammalian adipocytes and
      adrenocortical cells.
AB  - The hormone stanniocalcin (STC) is widely distributed, and in rodents the highest
      levels of expression are in the ovaries. In both cows and rodents, ovarian STC
      consists of three high-molecular-weight variants collectively known as big STC.
      In the ovary, big STC is made by theca cells and interstitial cells and is
      targeted to lipid storage droplets of nearby luteal cells to inhibit progesterone
      release. An endocrine pathway is operative during pregnancy and lactation.
      Whether or not big STC is made by tissues other than ovary has never been
      addressed. Therefore, the purpose of this study was to determine via a detailed
      characterization of adrenal glands and adipocytes whether big STC is present in
      other cells that store and release lipids. The results showed that STC was made
      in bovine and mouse adrenals, mainly in steroidogenic, adrenocortical cells. The
      majority of ligand and receptor were likewise confined to cortical zone cells. As
      in luteal cells, high levels of ligand and receptor were found in the
      adrenocortical cell lipid droplet fraction. However, adrenals made only the
      largest (135 kDa) of the three big STC variants. Nonetheless, adrenal STC had
      much greater receptor affinity than a mixture of the three big STC variants.
      Adipocytes contained all three big STC variants, and both ligand and receptor
      were heavily concentrated on the lipid droplets. Moreover, adipocyte lipid
      storage droplets had 50-fold more receptors than those in steroidogenic cells,
      indicating that big STC is heavily targeted to adipose cells. The findings
      collectively support the hypothesis that big STC is not unique to ovarian
      steroidogenic cells but is in fact common to cells with a role in lipid storage
      and release.

PMID- 15741243
TI  - Alpha-Ketoisocaproate-induced hypersecretion of insulin by islets from diabetes
      susceptible mice.
AB  - Most patients at risk for developing type 2 diabetes are hyperinsulinemic.
      Hyperinsulinemia may be a response to insulin resistance, but another possible
      abnormality is insulin hypersecretion. BTBR mice are insulin resistant and
      hyperinsulinemic. When the leptin(ob) mutation is introgressed into BTBR mice,
      they develop severe diabetes. We compared the responsiveness of lean B6 and BTBR
      mouse islets to various insulin secretagogues. The transamination product of
      leucine, alpha-ketoisocaproate (KIC), elicited a dramatic insulin secretory
      response in BTBR islets. The KIC response was blocked by methyl-leucine or
      aminooxyacetate, inhibitors of branched-chain amino transferase. When
      dimethylglutamate was combined with KIC, the fractional insulin secretion was
      identical in islets from both mouse strains, predicting that the amine donor is
      rate-limiting for KIC-induced insulin secretion. Consistent with this prediction,
      glutamate levels were higher in BTBR than in B6 islets. The transamination
      product of glutamate, alpha-ketoglutarate, elicited insulin secretion equally
      from B6 and BTBR islets. Thus formation of alpha-ketoglutarate is a requisite
      step in the response of mouse islets to KIC. alpha-Ketoglutarate can be oxidized
      to succinate. However, succinate does not stimulate insulin secretion in mouse
      islets. Our data suggest that alpha-ketoglutarate may directly stimulate insulin
      secretion and that increased formation of alpha-ketoglutarate leads to
      hyperinsulinemia.

PMID- 15741244
TI  - The vitamin D receptor is not required for fetal mineral homeostasis or for the
      regulation of placental calcium transfer in mice.
AB  - We utilized a vitamin D receptor (VDR) gene knockout model to study the effects
      of maternal and fetal absence of VDR on maternal fertility, fetal-placental
      calcium transfer, and fetal mineral homoeostasis. Vdr null mice were profoundly
      hypocalcemic, conceived infrequently, and had significantly fewer viable fetuses
      in utero that were also of lower body weight. Supplementation of a calcium
      enriched diet increased the rate of conception in Vdr nulls but did not normalize
      the number or weight of viable fetuses. Among offspring of heterozygous (Vdr(+/
      )) mothers (wild type, Vdr(+/-), and Vdr null fetuses), there was no alteration
      in serum Ca, P, or Mg, parathyroid hormone, placental (45)Ca transfer, Ca and Mg
      content of the fetal skeleton, and morphology and gene expression in the fetal
      growth plates. Vdr null fetuses did have threefold increased 1,25
      dihydroxyvitamin D levels accompanied by increased 1alpha-hydroxylase mRNA in
      kidney but not placenta; a small increase was also noted in placental expression
      of parathyroid hormone-related protein (PTHrP). Among offspring of Vdr null
      mothers, Vdr(+/-) and Vdr null fetuses had normal ionized calcium levels and a
      skeletal ash weight that was appropriate to the lower body weight. Thus our
      findings indicate that VDR is not required by fetal mice to regulate placental
      calcium transfer, circulating mineral levels, and skeletal mineralization.
      Absence of maternal VDR has global effects on fetal growth that were partly
      dependent on maternal calcium intake, but absence of maternal VDR did not
      specifically affect fetal mineral homeostasis.

PMID- 15741245
TI  - Recombinant human interleukin-6 infusion during low-intensity exercise does not
      enhance whole body lipolysis or fat oxidation in humans.
AB  - The present study examined the role of the cytokine IL-6 in the regulation of
      fatty acid metabolism during exercise in humans. Six well-trained males completed
      three trials of 120 min of cycle ergometry at 70% peak O(2) consumption (Vo(2
      peak); MOD) and 40% Vo(2 peak) with (LOW + IL-6) and without (LOW) infusion of
      recombinant human (rh)IL-6. The dose of rhIL-6 during LOW + IL-6 elicited IL-6
      concentration similar to those during MOD but without altering the circulating
      hormonal milieu seen in MOD. Palmitate rate of appearance (R(a)), rate of
      disappearance (R(d)), and oxidation were measured by means of a constant infusion
      of [U-(13)C]palmitate (0.015 micromol.kg(-1).min(-1), prime NaHCO(3), 1
      micromol/kg). Palmitate R(a), R(d), and oxidation were not affected by rhIL-6
      infusion, remaining similar to LOW at all times. Palmitate R(a) and oxidation
      were significantly greater in the MOD trial (P < 0.05) compared with the LOW + IL
      6 and LOW trials. Our data show that a low dose of rhIL-6, administered during
      low-intensity exercise without altering the hormonal milieu, does not alter fatty
      acid metabolism. These data suggest that the increase in fatty acid utilization
      seen during exercise at moderate compared with low intensity is not mediated via
      alterations in plasma IL-6.

PMID- 15741246
TI  - Protein structure topological comparison, discovery and matching service.
AB  - We describe a fold level fast protein comparison and motif matching facility
      based on the TOPS representation of structure. This provides an update to a
      previous service at the EBI, with a better graph matching with faster results and
      visualization of both the structures being compared against and the common
      pattern of each with the target domain. AVAILABILITY: Web service at
      http://balabio.dcs.gla.ac.uk/tops or via the main TOPS site at
      http://www.tops.leeds.ac.uk. Software is also available for download from these
      sites.

PMID- 15741247
TI  - Disulfide connectivity prediction using secondary structure information and
      diresidue frequencies.
AB  - MOTIVATION: We describe a stand-alone algorithm to predict disulfide bond
      partners in a protein given only the amino acid sequence, using a novel neural
      network architecture (the diresidue neural network), and given input of symmetric
      flanking regions of N-terminus and C-terminus half-cystines augmented with
      residue secondary structure (helix, coil, sheet) as well as evolutionary
      information. The approach is motivated by the observation of a bias in the
      secondary structure preferences of free cysteines and half-cystines, and by
      promising preliminary results we obtained using diresidue position-specific
      scoring matrices. RESULTS: As calibrated by receiver operating characteristic
      curves from 4-fold cross-validation, our conditioning on secondary structure
      allows our novel diresidue neural network to perform as well as, and in some
      cases better than, the current state-of-the-art method. A slight drop in
      performance is seen when secondary structure is predicted rather than being
      derived from three-dimensional protein structures.

PMID- 15741248
TI  - Clinical review: Diagnosis and management of pituitary carcinomas.
AB  - Pituitary carcinomas are rare, making up some 0.2% of all pituitary tumors, but
      represent a particular challenge to clinical practice. The diagnosis of a
      pituitary carcinoma requires evidence of metastatic disease, either outside the
      central nervous system (CNS) or as separate noncontiguous foci within the CNS.
      They may present as typical pituitary adenomas, which reveal their malignant
      character only as time progresses, or as peculiarly aggressive tumors ab initio.
      Recent changes in histopathological classification have clarified many of the
      features of such tumors, including immunohistochemical staining for Ki-67 and
      p53, but to date none has been found to be pathognomonic. The majority of
      carcinomas are secretory, usually arising from corticotroph tumors or
      prolactinomas, but all histological types and secretory patterns are represented.
      Treatment is by surgery, transsphenoidal wherever possible, and conventional and
      stereotactic radiotherapy, but ultimately, a plethora of therapies may be
      required, including various attempts at medical therapy. Chemotherapy in some
      instances probably prolongs survival, but, in general, their progress from the
      diagnosis of carcinomatous changes is progressive and inexorable. However, we do
      not believe there will be any real prospect of long-term survival until the
      development and use of therapies targeted at specific molecular abnormalities.

PMID- 15741250
TI  - Resistin levels in human immunodeficiency virus-infected patients with
      lipoatrophy decrease in response to rosiglitazone.
AB  - Resistin is a recently recognized adipocytokine thought to contribute to insulin
      resistance. We determined resistin levels and metabolic parameters in 24 HIV
      infected men and women with lipoatrophy and hyperinsulinemia and studied the
      effect of 12 wk of the peroxisome proliferator-activated receptor-gamma agonist
      rosiglitazone (4-8 mg/d) on resistin in these subjects. Participants completed
      metabolic testing before and after rosiglitazone including fasting determination
      of resistin, adiponectin, and leptin levels, serum inflammatory markers, and
      hyperinsulinemic euglycemic clamp testing. Resistin concentration decreased
      significantly after rosiglitazone (12.17 +/- 1.15 ng/ml to 10.23 +/- 1.05 ng/ml;
      P = 0.02), in conjunction with significant increases in adiponectin- (P < 0.001)
      and insulin- stimulated glucose disposal (P = 0.004). Leptin levels, as well as
      TNF-alpha, did not change with rosiglitazone. In summary, among HIV-infected
      subjects with insulin resistance and lipoatrophy, resistin levels decreased
      significantly after rosiglitazone. Further investigation into the physiological
      role of this peroxisome proliferator-activated receptor-gamma-responsive
      adipocytokine in the metabolic abnormalities associated with HIV is warranted.

PMID- 15741249
TI  - Effects of the human immunodeficiency virus-protease inhibitor, ritonavir, on
      basal and catecholamine-stimulated lipolysis.
AB  - Several of the aspartic acid protease inhibitors used to treat HIV infection
      increase basal lipolysis in adipocytes, but the cellular mechanisms leading to
      this augmentation are not well understood. We therefore studied the effects of
      chronic exposure to the HIV protease inhibitor, ritonavir, on the lipolytic
      cascade in 3T3-L1 adipocytes. Treatment of 3T3-L1 adipocytes with ritonavir for
      14 d (during and after differentiation) enhanced basal, isoproterenol (Iso)
      stimulated, and cAMP analog-stimulated lipolysis. Enhancement of lipolysis was
      observed after Iso at concentrations between 0.1 and 10 mum. Despite a
      significant decrease in cyclic nucleotide phosphodiesterase (PDE)3B activity and
      protein levels, there were no changes in Iso-stimulated intracellular cAMP,
      protein kinase A (PKA) expression, or PKA activity. Ritonavir-augmented lipolysis
      was also observed under conditions that reversed the effect on PDE3B activity via
      preincubation with 1 mum (-)-N(6)-(2-phenylisopropyl)adenosine. In ritonavir
      treated cells, protein expression of the lipid droplet-protective protein,
      perilipin, was significantly decreased, whereas there was no change in hormone
      sensitive lipase. Activation of ERK1/2 by Iso did not play a role in the
      augmentation. We conclude that ritonavir decreases PDE3B and perilipin protein
      expression and affects both basal and catecholamine-stimulated lipolysis in 3T3
      L1 adipocytes primarily through actions at sites downstream of PKA.

PMID- 15741252
TI  - Exogenous corticosteroids and in utero oxygenation modulate indices of fetal
      insulin secretion.
AB  - Low birth weight has long-term effects on glucose-insulin homeostasis. Factors
      that could mediate intra-uterine "programing" of glucose homeostasis include
      endogenous and exogenous glucocorticoids, adipose tissue-secreted factors such as
      adiponectin, and in utero hypoxia. Here, we studied 123 fetuses with gestational
      age (GA) between 25 and 37 wk and birth weight sd score (BW SDS) between -2.79
      and 2.42. We measured proinsulin, C-peptide, insulin, and adiponectin in
      umbilical vein (UV) plasma and calculated the proinsulin to insulin ratio as a
      measure of beta-cell secretory function. These indices were related to GA, BW
      SDS, time since the last maternal betamethasone administration, and blood gas
      data. Insulin and C-peptide were correlated with BW SDS but not GA, whereas the
      proinsulin to insulin ratio was inversely correlated with BW SDS. The proinsulin
      to insulin ratio was raised (P = 0.002) in fetuses with UV PO(2) less than or
      equal to 21.3 mm Hg (i.e. the 50th percentile) compared with those with PO(2)
      more than 21.3 mm Hg, inferring that in utero hypoxia engenders beta-cell
      secretory dysfunction. Proinsulin, insulin, and C-peptide were markedly but
      transiently (<24 h) elevated after maternal betamethasone administration,
      returning thereafter to concentrations measured in noncorticosteroid-treated
      fetuses. However, there was considerable variability within the less than 24-h
      betamethasone group: the indices of insulin secretion were related to UV PO(2),
      suggesting that hypoxia attenuates the responsiveness of fetal beta-cells to
      corticosteroids. Adiponectin was not related to any of the insulin indices. In
      conclusion, we have identified two environmental signals that modulate fetal
      insulin output: maternal corticosteroids produce a transient surge in fetal
      insulin synthesis and secretion, whereas in utero hypoxia disturbs the insulin
      secretory process.

PMID- 15741251
TI  - Graded inhibition of pulsatile luteinizing hormone secretion by a selective
      gonadotropin-releasing hormone (GnRH)-receptor antagonist in healthy men:
      evidence that age attenuates hypothalamic GnRH outflow.
AB  - Healthy older men manifest concomitant hypoandrogenemia and attenuation of LH
      pulse size. Because exogenous GnRH remains effective, a plausible intuition is
      that aging reduces hypothalamic GnRH secretion, thus mediating relative
      hypogonadotropic hypogonadism. To assess the impact of age on central GnRH
      outflow indirectly, we quantitated graded suppression of pulsatile LH secretion
      by saline and escalating doses of a potent and selective GnRH-receptor
      antagonist, ganirelix, in 18 healthy men ages 23-72 yr. The rationale is that
      ganirelix should reduce the amplitude of LH pulses in proportion to both drug
      concentration and endogenous GnRH feedforward. To this end, blood was sampled
      every 10 min for 2 h before and 16 h after sc administration of saline or
      ganirelix and for 3 additional hours after iv injection of a fixed dose of GnRH
      (100 ng/kg); concentrations of LH and ganirelix were measured by
      immunochemiluminometry and RIA, respectively; and pulsatile LH secretion was
      quantitated by a deconvolution procedure. Log-linear regression analysis was used
      to estimate the sensitivity of pulsatile LH secretion to inhibition by a unit
      increase in serum ganirelix concentrations in each subject. Statistical analyses
      revealed that increasing age markedly attenuated the capability of ganirelix to
      decrease LH pulse size (viz., r = -0.648; P = 0.004). In contrast, age did not
      modify the competitive interaction between injected GnRH and ganirelix. These
      joint outcomes support the clinical hypothesis that age diminishes hypothalamic
      GnRH outflow without impairing GnRH action in healthy men.

PMID- 15741253
TI  - Growth hormone and cortisol dynamic function in relation to birth weight: a study
      in adult twins.
AB  - Low birth weight (BW) is associated with an increased risk of the metabolic
      syndrome and cardiovascular disease in adulthood. Programmed hypersecretion of
      glucocorticoids or reduced secretion of GH has been postulated as mechanisms for
      this effect. However, other variables such as premature birth may confound the
      association of birth size with later endocrine function. To separate the effect
      of BW from other variables, we examined basal and dynamic function of the
      hypothalamus-pituitary-adrenal axis and GH-IGF axis in twin siblings with
      differing BW. Twenty pairs of same-sex healthy adult twins underwent measurement
      of serum cortisol before and after low-dose (1 mug) Synacthen stimulation, and
      plasma GH during glucose suppression and exercise stimulation. In paired
      statistical analysis, the lower BW twins had significantly lower morning serum
      cortisol than their heavier BW siblings (mean intrapair difference 60 nmol/liter,
      95% confidence interval 5-114, P < 0.03) but no difference in peak cortisol level
      after ACTH. Lower BW was associated with a trend to lower baseline plasma GH and
      a significantly lower peak GH concentration after exercise (difference 7.6
      mU/liter, 95% confidence interval 1.7-13.5, P = 0.01). Intrapair differences in
      basal and stimulated cortisol and basal GH also correlated significantly with the
      intrapair difference in BW, demonstrating a dose-response effect of BW on
      hypothalamus-pituitary-adrenal axis function and basal GH secretion. In a twin
      model that isolates BW from other confounding variables, our data suggest that
      low BW programs individuals for reduced GH secretion and reduced basal cortisol
      secretion but preservation of a cortisol secretory response to ACTH.

PMID- 15741254
TI  - Children experience cognitive decline despite reversal of brain atrophy one year
      after resolution of Cushing syndrome.
AB  - Adults with Cushing syndrome frequently develop brain atrophy, memory impairment,
      and depression, with partial to complete resolution after cure. The effect of
      excess glucocorticoid exposure on the brain of children has not been
      systematically studied. Eleven children (six girls, five boys; ages, 8-16 yr)
      with endogenous Cushing syndrome seen at the National Institutes of Health
      Clinical Center from 1999-2000 and 10 healthy age- and sex-matched control
      subjects were studied. Cognitive and psychological evaluations and magnetic
      resonance imaging of the brain were done before and 1 yr after cure for patients
      with Cushing syndrome and once for controls. The estimated duration of Cushing
      syndrome was 4.4 +/- 1.2 yr. When compared with control subjects, children with
      Cushing syndrome had significantly smaller cerebral volumes (P < 0.001), larger
      ventricles (P = 0.02), and smaller amygdala (P = 0.004). At baseline, there were
      no significant differences in IQ between the two groups, and no psychopathology
      was identified. Despite reversal of cerebral atrophy 1 yr after surgical cure
      (total cerebral volume, 947 +/- 94 vs.1050 +/- 74 ml, P < 0.001; ventricular
      volume, 21.4 +/- 12.5 vs. 14.5 +/- 11.6 ml, P < 0.001), children with Cushing
      syndrome experienced a significant (P < 0.05) decline in Wechsler IQ scores (Full
      Scale, 112 +/- 19 vs. 98 +/- 14) and a decline in school performance, without any
      associated psychopathology. The effect of glucocorticoid excess on the brain of
      children appears to be different from adults. Despite rapid reversibility of
      cerebral atrophy, children experience a significant decline in cognitive function
      1 yr after correction of hypercortisolism.

PMID- 15741255
TI  - Hereditary leiomyomatosis associated with bilateral, massive, macronodular
      adrenocortical disease and atypical cushing syndrome: a clinical and molecular
      genetic investigation.
AB  - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant
      disorder caused by mutations in the fumarate hydratase (FH) gene on chromosome
      1q42.3-43. Massive macronodular adrenocortical disease (MMAD) is a heterogeneous
      condition associated with Cushing syndrome (CS) and bilateral hyperplasia of the
      adrenal glands. In MMAD, cortisol secretion is often mediated by ectopic,
      adrenocortical expression of receptors for a variety of substances; however, to
      date, no consistent genetic defects have been identified. In a patient with HLRCC
      caused by a germline-inactivating FH mutation, we diagnosed atypical
      (subclinical) CS due to bilateral, ACTH-independent adrenocortical hyperplasia. A
      clinical protocol for the detection of ectopic expression of various hormone
      receptors was employed. Histology was consistent with MMAD. The tumor tissue
      harbored the germline FH mutation and demonstrated allelic losses of the 1q42.3
      43 FH locus. We then searched the National Institutes of Health (NIH) databases
      of patients with MMAD or HLRCC and found at least three other cases with MMAD
      that had a history of tumors that could be part of HLRCC; among patients with
      HLRCC, there were several with some adrenal nodularity noted on computed
      tomography but none with imaging findings consistent with MMAD. From two of the
      three MMAD patients, adrenocortical tumor DNA was available and sequenced for
      coding FH mutations; there were none. We conclude that in a patient with HLRCC,
      adrenal hyperplasia and CS were due to MMAD. The latter was likely due to the FH
      germline mutation because in tumor cells, only the mutant allele was retained.
      However, other patients with MMAD and HLRCC, or HLRCC patients with adrenal
      imaging findings consistent with MMAD, or MMAD patients with somatic FH mutations
      were not found among the NIH series. Although a fortuitous association cannot be
      excluded, HLRCC may be added to the short list of monogenic disorders that have
      been reported to be associated with the development of adrenal tumors; FH may be
      considered a candidate gene for MMAD.

PMID- 15741256
TI  - Association of hyperandrogenemic and metabolic phenotype with carotid intima
      media thickness in young women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of
      reproductive age, is associated with the early appearance of multiple risk
      factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and
      diabetes mellitus. However, premature atherosclerosis of the carotid artery has
      not yet been demonstrated in young women with PCOS. Measurement of carotid intima
      media thickness (IMT) is considered an easy and reliable index of subclinical
      atherosclerosis, which is predictive of subsequent myocardial infarction and
      stroke. To evaluate the cardiovascular risk of PCOS and the participation of the
      hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode
      ultrasound as well as hormonal and several cardiovascular disease-associated
      parameters in 75 young women with PCOS and 55 healthy, age- and body mass index
      matched women. The PCOS women had significantly increased carotid IMT (0.58 vs.
      0.47 mm, P < 0.001) and abdominal adiposity; higher levels of androgens, insulin,
      homeostasis model assessment score of insulin sensitivity, and total and low
      density lipoprotein-cholesterol; and significantly lower levels of SHBG and high
      density lipoprotein-cholesterol. In the studied population (n = 130), PCOS
      status, age, body mass index, and parental history of coronary heart disease were
      strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate
      was a strong negative predictor. In PCOS patients lower delta4-androstenedione
      and high-density lipoprotein-cholesterol levels were additionally strong positive
      predictors of carotid IMT, whereas in control women only total cholesterol was
      the additional positive predictor of carotid IMT. In conclusion, young women with
      PCOS have an early increase of cardiovascular risk factors and greater carotid
      IMT, both of which may be responsible for subclinical atherosclerosis. The
      hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the
      dysmetabolic phenotype on the vascular wall.

PMID- 15741257
TI  - Morbidity after long-term remission for acromegaly: persisting joint-related
      complaints cause reduced quality of life.
AB  - Active acromegaly is associated with significant comorbidity and reduced quality
      of life. However, the prevalence of comorbidity after long-term remission is not
      established. Therefore, we assessed the presence of comorbidity in 118 patients
      in long-term remission after surgery, radiotherapy, and/or somatostatin analog
      treatment according to strict biochemical criteria of serum GH and IGF-I
      concentrations and evaluated the impact of comorbidity on quality of life. The
      mean duration of remission was 12.0 +/- 7.4 yr, and mean actual IGF-I sd scores
      were 0.6 +/- 1.7. Self-reported joint problems occurred in 77% of patients,
      hypertension in 37%, a history of myocardial infarction in 9%, and diabetes
      mellitus in 11%. The presence of joint problems was not related to GH and IGF-I
      levels, active disease duration, or age. Joint complaints had significant
      negative impact on quality of life. Patients with a history of myocardial
      infarction had reduced scores for general health, depression, and fatigue, and
      diabetes mellitus was associated with reduced scores for anxiety and sleep. In
      conclusion, acromegalic patients had a high prevalence of joint-related
      comorbidity and hypertension despite long-term control of GH excess. Especially,
      joint complaints contributed to a reduced perceived quality of life in these
      patients.

PMID- 15741258
TI  - Antibody response to inhaled insulin in patients with type 1 or type 2 diabetes.
      An analysis of initial phase II and III inhaled insulin (Exubera) trials and a
      two-year extension trial.
AB  - OBJECTIVE: To compare antibody responses to inhaled human insulin vs. sc human
      insulin and to determine whether insulin antibody binding is associated with
      adverse clinical consequences. RESEARCH DESIGN AND METHODS: Insulin antibody data
      from initial phase II/III trials were analyzed comparing the efficacy and safety
      of inhaled insulin with various agents, including sc insulin. Additionally, data
      from a 24-month extension of the phase III studies were examined. Data were
      pooled into the following three groups based on insulin treatment status at
      baseline: patients with type 1 diabetes, and patients with type 2 diabetes using
      insulin and not using insulin at baseline. Ig class analysis was also performed
      on randomly selected sera from type 1 patients at the end of the initial trials.
      RESULTS: In the initial trials, greater insulin antibody binding was observed in
      patients receiving inhaled insulin vs. sc insulin. The greatest antibody
      responses to inhaled insulin were observed in patients with type 1 diabetes
      [nonparametric comparison of medians at the end of the study, 22.0% binding
      (unadjusted 95% confidence interval: 19.5, 24.5)], and the lowest responses were
      observed in non-insulin-using patients with type 2 diabetes in which there was no
      difference in median values at the end of the study. There were no correlations
      between antibody binding and glycemic control (measured using glycosylated
      hemoglobin), insulin dose requirements, hypoglycemic events, or pulmonary
      function (measured by changes in forced expiratory volume in 1 sec and diffusion
      capacity of carbon monoxide). Antibody responses were IgG in type. Differences in
      antibody levels observed in patients with type 1 vs. type 2 diabetes were
      maintained over the 24-month extension trials. Peak antibody levels across all
      groups were generally observed after 6-12 months of insulin therapy. Inhaled
      insulin therapy was not associated with a greater incidence of allergy or other
      hypersensitivity reactions. CONCLUSION: Inhaled insulin was observed to produce a
      larger antibody response than sc insulin. Insulin antibody binding has not been
      associated with adverse clinical consequences in trials to date.

PMID- 15741259
TI  - Multiple SNPs in intron 7 of thyrotropin receptor are associated with Graves'
      disease.
AB  - Our previous studies using microsatellite markers near or in the TSH receptor
      (TSHR) gene revealed significant association between autoimmune thyroid disease
      (AITD) in Japanese patients and TSHR microsatellite alleles. In the present
      study, we performed a case-control analysis of AITD using single-nucleotide
      polymorphisms (SNPs) spaced 3-50 kb apart spanning the TSHR gene. We observed
      significant associations between AITD/Graves' disease (GD)/Hashimoto's
      thyroiditis and multiple SNPs. Specifically, the SNP JST022302 and several
      adjacent SNPs in intron 7 of the TSHR gene were significantly associated with GD
      (P = 0.039-0.0004) but not Hashimoto's thyroiditis. Furthermore, we identified
      three haplotype blocks around intron 7 by linkage disequilibrium analysis. A
      single SNP haplotype [AATG(CT)6(TT)AG] in the haplotype block including JST022302
      showed significant association with GD in haplotype case-control analysis (P =
      0.0058). These findings suggest that alleles of intron 7 of the TSHR gene
      contribute to GD susceptibility.

PMID- 15741260
TI  - Sex-specific and non-sex-specific quantitative trait loci contribute to normal
      variation in bone mineral density in men.
AB  - INTRODUCTION: A major determinant of osteoporotic fracture is peak bone mineral
      density (BMD). In women peak BMD is highly heritable and several quantitative
      trait loci (QTL) have been reported. There are few comparable data in men. This
      study in men aimed to establish the heritability of peak BMD, identify QTL
      contributing to normal variation in BMD, and determine which QTL might be sex
      specific. METHODS: BMD at the spine and hip were measured in 323 pairs of
      brothers aged 18-61 yr (264 white pairs; 59 black pairs). Heritability was
      calculated and linkage analysis performed with spine and hip BMD phenotypes.
      RESULTS: Heritability estimates ranged from 0.61 to 0.87 and were not
      significantly different between white and black men. A 9-cM genome-wide scan
      followed by genotyping with more closely spaced markers identified suggestive QTL
      (logarithm of the odds > 2.2) for BMD on chromosomes 1q (spine), 2p (spine), 2q
      (hip), 14p (spine), 18 (hip), and 21 (hip). Comparison with published data in 774
      pairs of premenopausal sisters suggested that the QTL on 1q (spine), 2q (hip),
      14p (spine), and 21q (hip) were male specific, whereas those on 2p (spine) and 18
      (hip) were not sex specific. CONCLUSIONS: This study demonstrates that BMD in
      healthy men is highly heritable with similar estimates of the genetic
      contribution to BMD in both whites and blacks. Of the six QTL identified, three
      were specific for spine BMD and three were specific for hip BMD. When compared
      with published QTL for peak BMD in women from the same geographical region, four
      of the QTL appeared to be male specific. The occurrence of sex-specific genes in
      humans for BMD has potentially important implications for the pathogenesis and
      treatment of osteoporosis.

PMID- 15741261
TI  - Sympathetic modulation by carvedilol and losartan reduces angiotensin II-mediated
      lipolysis in subcutaneous and visceral fat.
AB  - Advanced heart failure is characterized by increased activation of the renin
      angiotensin system and the development of cachexia. Angiotensin II (Ang II) has
      been proposed as a lipid metabolism regulator. The effects of exogenous Ang II
      (osmotic minipump, 525 ng/kg/min for 12 d) on interstitial sc glycerol and
      norepinephrine levels, indexes of lipolysis, and sympathetic activation,
      respectively, were measured in Sprague Dawley rats by consecutive microdialysis
      performed in vivo in white adipose tissue. Higher sustained interstitial glycerol
      and norepinephrine levels were found after 7 and 12 d of Ang II infusion.
      Triglyceride to DNA content ratio and adipocyte diameter were reduced in sc and
      visceral (retroperitoneal and epididymal) fat tissues of Ang II-infused rats,
      whose body weight was lower and blood pressure higher. Losartan, an Ang II
      receptor 1 blocker, and carvedilol, an alpha1-nonselective-beta1,2,3-adrenergic
      blocker, but not doxazosin, an alpha1-selective-adrenergic blocker, lowered
      glycerol and norepinephrine levels, preventing lipolysis and weight loss. Our
      results indicate that Ang II stimulates lipolysis in sc and visceral adipocytes
      by sympathetic activation and beta-adrenergic-receptor stimulation. Nonselective
      beta-adrenergic and Ang II-receptor1 blockade markedly attenuated the rise of
      norepinephrine, preventing catabolic effects. The metabolic benefits of
      carvedilol and losartan, in addition to recognized protective cardiovascular
      effects, may be relevant in cachectic patients with advanced heart failure.

PMID- 15741262
TI  - Dietary fat content modifies liver fat in overweight nondiabetic subjects.
AB  - BACKGROUND: Fat accumulation in the liver has been shown to be closely correlated
      with hepatic insulin resistance and features of insulin resistance, even
      independent of body weight. The reason for interindividual variation in liver fat
      content is unknown. Cross-sectional data suggest that dietary fat content may
      influence liver fat, but this possibility has not been directly tested in humans.
      DESIGN AND METHODS: Liver fat (proton spectroscopy), intraabdominal and sc fat
      (magnetic resonance imaging), and markers of insulin sensitivity (insulin, free
      fatty acids, and lipids) were determined in 10 normal, obese women (age, 43 +/- 5
      yr, mean +/- sd; body mass index, 33 +/- 4 kg/m2; range, 27-38 kg/m2) at baseline
      and after two 2-wk isocaloric periods containing either 16% (low-fat diet) or 56%
      (high-fat diet) of total energy as fat. RESULTS: Liver fat at baseline averaged
      10 +/- 7%. It decreased by 20 +/- 9% during the low-fat diet and increased by 35
      +/- 21% during the high-fat diet (P = 0.014 for liver fat after low- vs. high-fat
      diets; P = 0.042 for change in liver fat by the low- vs. high-fat diet). Fasting
      serum insulin averaged 70 +/- 41 pmol/liter at baseline. It decreased to 60 +/-
      24 pmol/liter during the low-fat diet (P = 0.007 vs. before low-fat diet) and
      increased to 81 +/- 44 pmol/liter during the high-fat diet (P = 0.040 vs. before
      high-fat diet; P = 0.005 for change in serum insulin during low- vs. high-fat
      diet). Serum lipids, free fatty acids, and intraabdominal and sc fat masses were
      unchanged. CONCLUSION: These data suggest that the amount of dietary fat
      influences liver fat content.

PMID- 15741263
TI  - Lipid mobilization with physiological atrial natriuretic peptide concentrations
      in humans.
AB  - CONTEXT: Atrial natriuretic peptide (ANP) in pharmacological concentrations
      stimulates lipid mobilization in humans. OBJECTIVE: The objective was to
      determine the hemodynamic and metabolic response to physiologically relevant ANP
      concentrations. DESIGN: The design was a human physiological study, conducted in
      2004. SETTING: The study was conducted at an academic research institute.
      PARTICIPANTS: Fourteen healthy normal-weight men (30 +/- 1.2 yr) participated in
      the study. INTERVENTION: Intravenous infusion of human ANP (h-ANP) was
      administered at rates of 6.25, 12.5, and 25 ng/kg.min. MAIN OUTCOME MEASURES: We
      studied local changes in blood flow and glucose and lipid metabolism of abdominal
      sc adipose tissue and femoral skeletal muscle by microdialysis. Overall changes
      in energy expenditure and substrate oxidation rates were monitored by indirect
      calorimetry. RESULTS: The increase in serum nonesterified fatty acids and
      glycerol concentrations were correlated with ANP plasma concentrations (r(2) =
      0.86 and r(2) = 0.76, respectively). In adipose tissue, glycerol increased from
      53 +/- 6 micromol/liter to 87+/-13 micromol/liter (P < 0.001). In femoral
      skeletal muscle, glycerol concentrations did not change, whereas lactate-to
      pyruvate ratio decreased from 91 +/- 23 to 32 +/- 4 (P < 0.001). Indirect
      calorimetry indicated an increase in lipid oxidation (P < 0.05) concomitantly
      with a decrease in carbohydrate oxidation (P < 0.01), without changes in overall
      energy expenditure. CONCLUSIONS: ANP briskly stimulates lipid mobilization and
      oxidation at plasma concentrations that are encountered in conditions such as
      heart failure. Natriuretic-peptide induced lipid mobilization might contribute to
      cardiac cachexia. Drugs that interfere with the natriuretic peptide system should
      be evaluated for potential metabolic side effects.

PMID- 15741264
TI  - Growth hormone replacement is important for the restoration of parathyroid
      hormone sensitivity and improvement in bone metabolism in older adult growth
      hormone-deficient patients.
AB  - Alterations in PTH circadian rhythm and PTH target-organ sensitivity exist in
      adult GH-deficient (AGHD) patients and may underlie the pathogenesis of AGHD
      related osteoporosis. GH replacement (GHR) results in increased bone mineral
      density, but its benefit in AGHD patients over 60 yr old has been debated. To
      examine the effect of age on changes in PTH circadian rhythm and target-organ
      sensitivity after GHR, we recruited 22 AGHD patients (12 were <60 yr of age, and
      10 were >60 yr of age). Half-hourly blood samples were collected for PTH,
      calcium, phosphate, nephrogenous cAMP (marker of renal PTH activity), type-I
      collagenbeta C-telopeptide (bone resorption marker), and procollagen type-I amino
      terminal propeptide (bone formation marker) before and after 1, 3, 6, and 12
      months of treatment with GHR. Significant PTH circadian rhythms were present in
      both age groups throughout the study. After GHR, PTH decreased and nephrogenous
      cAMP, adjusted calcium, and bone turnover markers increased in both groups,
      suggesting increased PTH target-organ sensitivity. In younger patients, the
      changes were significant after 1 month of GHR, but, in older patients, the
      changes were delayed until 3 months, with maximal changes at 12 months. Older
      AGHD patients derive benefit from GHR in terms of improvement in PTH sensitivity
      and bone metabolism. Their response appears delayed and may explain why previous
      studies have not shown a positive effect of GHR on bone mineral density in older
      AGHD patients.

PMID- 15741265
TI  - Germline homozygous mutations at codon 804 in the RET protooncogene in medullary
      thyroid carcinoma/multiple endocrine neoplasia type 2A patients.
AB  - The effect of mutations at codon 804 in the RET protooncogene is disputed. Some
      studies have suggested that the V804L mutation causes the low penetrance multiple
      endocrine neoplasia type 2 syndrome, with late onset and relatively indolent
      course, whereas others have reported that V804L and V804M have an aggressive
      potential. In this paper, we report three apparently unrelated medullary thyroid
      carcinoma cases homozygous for these mutations. To clarify the phenotypic
      heterogeneity associated with these mutations, we compare the clinical data and
      age of diagnosis among these three homozygous patients, six other heterozygous
      cases from the same populations, and other homozygous and heterozygous subjects
      reported previously. The data are consistent with a model in which codon 804
      mutations have low penetrance, the developing of medullary thyroid carcinoma
      being associated with a second germline or somatic mutation. The activity and (in
      the case of somatic mutations) timing of these other genetic alterations in the
      RET gene may explain the wide clinical variability associated with germline
      mutations at codon 804.

PMID- 15741266
TI  - Low-fat high-fiber diet decreased serum and urine androgens in men.
AB  - To validate our hypothesis that reduction in dietary fat may result in changes in
      androgen metabolism, 39 middle-aged, white, healthy men (50-60 yr of age) were
      studied while they were consuming their usual high-fat, low-fiber diet and after
      8 wk modulation to an isocaloric low-fat, high-fiber diet. Mean body weight
      decreased by 1 kg, whereas total caloric intake, energy expenditure, and activity
      index were not changed. After diet modulation, mean serum testosterone (T)
      concentration fell (P < 0.0001), accompanied by small but significant decreases
      in serum free T (P = 0.0045), 5 alpha-dihydrotestosterone (P = 0.0053), and
      adrenal androgens (androstendione, P = 0.0135; dehydroepiandrosterone sulfate, P
      = 0.0011). Serum estradiol and SHBG showed smaller decreases. Parallel decreases
      in urinary excretion of some testicular and adrenal androgens were demonstrated.
      Metabolic clearance rates of T were not changed, and production rates for T
      showed a downward trend while on low-fat diet modulation. We conclude that
      reduction in dietary fat intake (and increase in fiber) results in 12% consistent
      lowering of circulating androgen levels without changing the clearance.

PMID- 15741267
TI  - Quality of life in patients after long-term biochemical cure of Cushing's
      disease.
AB  - To evaluate the long-term impact of cured Cushing's disease on subjective well
      being, we assessed quality of life by validated health-related questionnaires in
      58 patients cured from Cushing's disease by transsphenoidal surgery (n = 58),
      some of whom received additional radiotherapy (n = 11) and/or bilateral
      adrenalectomy (n = 3). The mean duration of remission was 13.4 +/- 6.7 yr (range
      of 2-25 yr). Patient data were compared with a control group of 98 healthy
      subjects with the same age and sex distribution and with age-adjusted reference
      values available from the literature. General perceived well-being, measured by
      the Nottingham Health Profile and the Short Form, was reduced compared with
      controls for all subscales (P < 0.001). Patients with Cushing's disease had worse
      scores on subscales of fatigue Multidimensional Fatigue Index and anxiety and
      depression (Hospital Anxiety and Depression Scale). Compared with reference
      values from the literature, quality of life was also reduced in the patients
      according to all questionnaires and all items, except pain (Short Form), sleep
      (Nottingham Health Profile), and reduced activity (Multidimensional Fatigue
      Index). Despite conventional hormone replacement therapy, hypopituitarism was an
      important independent predictor of reduced quality of life. Patients without
      hypopituitarism (n = 28) showed reduced scores on physical items but normal
      scores on mental items compared with controls. In conclusion, despite long-term
      cure of Cushing's disease, patients experience a considerable decrease in quality
      of life, with physical and psychosocial impairments, especially in the presence
      of hypopituitarism.

PMID- 15741268
TI  - Sex hormone suppression reduces resting energy expenditure and {beta}-adrenergic
      support of resting energy expenditure.
AB  - Resting energy expenditure (REE) decreases with aging and may decrease in women
      as a result of the menopause, potentially contributing to weight gain. REE has
      been observed to fluctuate during the menstrual cycle, suggesting regulation by
      sex hormones. The aim of the present study was to determine the effects of
      suppressing estrogen and progesterone on REE. Fourteen premenopausal women, 29 +/
      5 yr old (mean +/- sd), were studied in the midluteal menstrual phase (ML) and
      after 6 d of GnRH antagonist therapy (GnRHant) administered in the follicular
      menstrual phase. REE was measured by indirect calorimetry in the morning after a
      12-h fast and again during beta-adrenergic blockade to determine sympathetic
      nervous system (SNS) support of REE. Treatment with GnRHant significantly
      decreased REE (1405 +/- 42 vs. 1334 +/- 36 kcal/d, mean +/- se, ML vs. GnRHant; P
      = 0.002). Additionally, SNS blockade tended to alter REE more during ML than
      during GnRHant (-19 +/- 10 vs. 5 +/- 11 kcal/d; P = 0.14). Suppression of sex
      hormones to postmenopausal levels by GnRHant reduced REE in young healthy women.
      These findings suggest that the withdrawal of estrogen and/or progesterone
      attenuates REE, possibly through a SNS-mediated mechanism.

PMID- 15741269
TI  - Deletion mapping of chromosome 17 in benign and malignant adrenocortical tumors
      associated with the Arg337His mutation of the p53 tumor suppressor protein.
AB  - The human p53 tumor suppressor gene is located at the short arm of chromosome 17.
      A germinative mutation (Arg337His) in the tetramerization domain of p53 has been
      frequently identified in Brazilian children with sporadic adrenocortical tumors.
      Loss of heterozygosity at this region was demonstrated in the majority of the
      cases. In the present study, we performed deletion mapping of chromosome 17 in 30
      adrenocortical tumors from 29 Brazilian patients (15 children and 14 adults). One
      boy had bilateral adrenocortical tumor. Sixteen patients had the germinative
      Arg337His mutation. Loss of heterozygosity analysis using six polymorphic
      microsatellite markers disclosed loss of the entire chromosome 17 in 18 tumors
      (10 adenomas and eight carcinomas) from 17 patients. The Arg337His mutation was
      present in 13 of them. Chromosomal instability involving chromosomes 2, 9, and 11
      was also found in 47, 47, and 70% of the 17 patients who exhibited chromosome 17
      losses, respectively. The concomitant loss of chromosomes 2, 9, 11, and 17 was
      evidenced exclusively in malignant tumors. Therefore, chromosomal instability
      involving three or more chromosomes may contribute to define the malignant
      adrenocortical lesions. In conclusion, we demonstrated a high frequency of
      biallelic inactivation of p53 derived from two distinct events, the germinative
      Arg337His mutation and the acquired loss of the entire chromosome 17. In
      addition, the isolated loss of the entire chromosome 17 did not correlate with
      aggressive tumor behavior in these patients with adrenocortical tumors.

PMID- 15741270
TI  - Evolutionary profiles from the QR factorization of multiple sequence alignments.
AB  - We present an algorithm to generate complete evolutionary profiles that represent
      the topology of the molecular phylogenetic tree of the homologous group. The
      method, based on the multidimensional QR factorization of numerically encoded
      multiple sequence alignments, removes redundancy from the alignments and orders
      the protein sequences by increasing linear dependence, resulting in the
      identification of a minimal basis set of sequences that spans the evolutionary
      space of the homologous group of proteins. We observe a general trend that these
      smaller, more evolutionarily balanced profiles have comparable and, in many
      cases, better performance in database searches than conventional profiles
      containing hundreds of sequences, constructed in an iterative and computationally
      intensive procedure. For more diverse families or superfamilies, with sequence
      identity <30%, structural alignments, based purely on the geometry of the protein
      structures, provide better alignments than pure sequence-based methods. Merging
      the structure and sequence information allows the construction of accurate
      profiles for distantly related groups. These structure-based profiles
      outperformed other sequence-based methods for finding distant homologs and were
      used to identify a putative class II cysteinyl-tRNA synthetase (CysRS) in several
      archaea that eluded previous annotation studies. Phylogenetic analysis showed the
      putative class II CysRSs to be a monophyletic group and homology modeling
      revealed a constellation of active site residues similar to that in the known
      class I CysRS.

PMID- 15741271
TI  - Stable isotope-free relative and absolute quantitation of protein phosphorylation
      stoichiometry by MS.
AB  - Qualitative and quantitative information are crucial to a detailed understanding
      of the function of protein phosphorylation. MS is now becoming a quantitative
      approach to analyze protein phosphorylation. All methods that have been described
      either require the elaborate/expensive use of stable isotopes to compare a
      limited number of samples or do not provide phosphorylation stoichiometries.
      Here, we present stable isotope-free MS strategies that allow relative and
      absolute quantitation of phosphorylation stoichiometries. By using the developed
      methods, we can normalize to robustly account for run-to-run variations and
      variations in amounts of starting material. This procedure monitors the
      unmodified proteolytic peptides derived from the protein of interest and
      identifies peptides that are suitable for normalization purposes. Also, we can
      determine changes in phosphorylation stoichiometry by monitoring the changes in
      the normalized ion currents of the phosphopeptide(s) of interest. Absolute
      phosphorylation stoichiometry are measured by monitoring the ion currents of a
      phosphopeptide and its unmodified cognate as the signal intensity changes of both
      peptide species are correlated. The method is applicable to multiply
      phosphorylated species (for which one more sample with varying phosphorylation
      stoichiometry than number of phosphorylation sites is required to correct for the
      differences in the ionization/detection efficiencies of the phosphopeptide, its
      partially phosphorylated and unphosphorylated cognates). Last, we can quantitate
      species with ragged ends resulting from incomplete proteolysis and measure
      phosphorylation stoichiometries of single samples by controlled
      dephosphorylation. These approaches were validated and subsequently applied to
      the phosphorylation of the yeast transcription factor Pho4.

PMID- 15741272
TI  - Helminth regulation of host IL-4Ralpha/Stat6 signaling: mechanism underlying NOS
      2 inhibition by Trichinella spiralis.
AB  - Gastrointestinal nematode infection is known to alter host T cell activation and
      has been used to study immune and inflammatory reactions in which nitric oxide
      (NO) is a versatile player. We previously demonstrated that Trichinella spiralis
      infection inhibits host inducible NO synthase (NOS-2) expression. We now
      demonstrate that (i) an IL-4 receptor alpha-subunit (IL-4Ralpha)/Stat6-dependent
      but T cell-independent pathway is the key for the nematode-induced host NOS-2
      inhibition; (ii) endogenous IL-4 and IL-13, the only known IL-4Ralpha ligands,
      are not required for activating the pathway; and (iii) treatment of RAW264.7
      cells with parasite-cultured medium inhibits NOS-2 expression but not
      cyclooxygenase 2 expression. We propose that a yet-unidentified substance is
      released by the nematode during the host-parasite interaction.

PMID- 15741273
TI  - Rotavirus nonstructural protein 1 subverts innate immune response by inducing
      degradation of IFN regulatory factor 3.
AB  - IFN regulatory factor 3 (IRF3), a constitutively expressed protein localizing
      largely to the cytoplasm, is a primary effector of the innate immune response.
      Infection can trigger the phosphorylation, dimerization, and nuclear
      translocation of IRF3, where the factor stimulates the expression and release of
      IFN. In this study, we determined that the rotavirus gene 5 product,
      nonstructural protein 1 (NSP1), interacts with IRF3 in the infected cell. To
      understand the importance of the interaction, we compared IRF3 activation by
      rotaviruses expressing wild-type and C-truncated forms of NSP1. The analysis
      showed that IRF3 underwent dimerization and nuclear translocation and stimulated
      IFN promoter activity in infected cells expressing truncated NSP1. In contrast,
      infected cells expressing wild-type NSP1 were characterized by the rapid
      degradation of IRF3 during the replication cycle, severe decreases in IRF3
      dimerization and nuclear translocation, and lack of IFN promoter activity. The
      implication of these results, that wild-type NSP1 is an antagonist of the IFN
      signaling pathway, was confirmed in transient expression assays, which showed
      that wild-type NSP1, but not the C-truncated protein, induced the degradation of
      IRF3 fusion proteins. Related experiments indicated that NSP1 mediates IRF3
      degradation through a proteasome-dependent pathway. The critical role of NSP1 in
      promoting cell-to-cell spread of rotavirus was demonstrated by using gene 5
      specific short interfering RNAs in plaque assays. Although several viruses have
      been described that subvert the innate immune response by preventing IRF3
      activation, rotavirus is identified as one that accomplishes this task by
      inducing the degradation of IRF3.

PMID- 15741274
TI  - Quantifying the mechanisms for segmental duplications in mammalian genomes by
      statistical analysis and modeling.
AB  - A large number of the segmental duplications in mammalian genomes have been
      cataloged by genome-wide sequence analyses. The molecular mechanisms involved in
      these duplications mostly remain a matter of speculation. To uncover, test, and
      further quantify the hypotheses on the mechanisms for the recent duplications in
      the mammalian genomes, we have performed a series of statistical analyses on the
      sequences flanking the duplicated segments and proposed a dynamic model for the
      duplication process. The model, when applied to the human duplication data,
      indicates that approximately 30% of the recent human segmental duplications were
      caused by a recombination-like mechanism, among which 12% were mediated by the
      most recently active repeat, Alu. But a significant proportion of the
      duplications are caused by some mechanism independent of the repeat distribution.
      A less sure but similar picture is found in the rodent genomes. A further
      analysis on the physical features of the flanking sequences suggests that one of
      the uncharacterized duplication mechanisms shared by the mammalian genomes is
      surprisingly well correlated with the physical instability in the DNA sequences.

PMID- 15741277
TI  - Shared phenotypes among segmental progeroid syndromes suggest underlying pathways
      of aging.
AB  - Segmental progeroid syndromes are those whose phenotypes resemble accelerated
      aging. Here we analyze those phenotypes and hypothesize that short telomeres
      produce the same group of symptoms in a variety of otherwise unrelated progeroid
      syndromes. Specific findings are the following: (a) short telomeres in some
      progeroid syndromes cause an alopecia/osteoporosis/fingernail-atrophy group of
      symptoms; (b) fingernail atrophy in progeroid syndromes resembles the natural
      slowing of nail growth that occurs in normal aging and nail growth velocity, and
      may be a marker of replicative aging in keratinocyte stem cells; (c) alopecia and
      reduced hair diameter parallel the nail results; (d) osteoporosis in Dyskeratosis
      Congenita resembles age-related osteoporosis, but the same is not true of other
      progerias; and (e) gray hair is associated with short telomeres, but may also
      involve reactive oxygen species. On the basis of these results, we make several
      predictions and discuss how the segmental quality of progeroid syndromes may
      provide insight into normative aging.

PMID- 15741276
TI  - Down-regulation of a forkhead transcription factor, FOXO3a, accelerates cellular
      senescence in human dermal fibroblasts.
AB  - The signaling pathway of insulin/insulin-like growth factor/phosphatidylinositol
      3 kinase/Akt/forkhead transcription factors is known to control life span and
      senescence in organisms ranging from yeast to mice. The FOXO family of forkhead
      transcription factors, FOXO1, FOXO3a, and FOXO4, play a critical role in this
      signal transduction pathway. However, the impact of FOXO3a activation on life
      span of primary cultured human dermal fibroblasts (HDFs) is unknown. To
      investigate the role of FOXO3a in the regulation of cellular senescence, we
      prepared FOXO3a-siRNA stable HDFs. We found that the down-regulation of FOXO3a
      RNA and protein in HDFs induced many senescent phenotypes, including changes in
      cell morphology, increases in population doubling times, senescence-associated
      beta-galactosidase staining and the cellular reactive oxygen species, and up
      regulation of p53/p21 protein expression. Our data provide evidence of the key
      role of FOXO3a transcription factor as a mediator of cellular senescence in HDFs,
      and suggest that the mechanism of senescence is conserved in HDFs.

PMID- 15741275
TI  - Diagnosis of human prion disease.
AB  - With the discovery of the prion protein (PrP), immunodiagnostic procedures were
      applied to diagnose Creutzfeldt-Jakob disease (CJD). Before development of the
      conformation-dependent immunoassay (CDI), all immunoassays for the disease
      causing PrP isoform (PrPSc) used limited proteolysis to digest the precursor
      cellular PrP (PrPC). Because the CDI is the only immunoassay that measures both
      the protease-resistant and protease-sensitive forms of PrPSc, we used the CDI to
      diagnose human prion disease. The CDI gave a positive signal for PrPSc in all 10
      24 brain regions (100%) examined from 28 CJD patients. A subset of 18 brain
      regions from 8 patients with sporadic CJD (sCJD) was examined by histology,
      immunohistochemistry (IHC), and the CDI. Three of the 18 regions (17%) were
      consistently positive by histology and 4 of 18 (22%) by IHC for the 8 sCJD
      patients. In contrast, the CDI was positive in all 18 regions (100%) for all 8
      sCJD patients. In both gray and white matter, approximately 90% of the total
      PrPSc was protease-sensitive and, thus, would have been degraded by procedures
      using proteases to eliminate PrPC. Our findings argue that the CDI should be used
      to establish or rule out the diagnosis of prion disease when a small number of
      samples is available as is the case with brain biopsy. Moreover, IHC should not
      be used as the standard against which all other immunodiagnostic techniques are
      compared because an immunoassay, such as the CDI, is substantially more
      sensitive.

PMID- 15741278
TI  - Aging elevates basal adenosine monophosphate-activated protein kinase (AMPK)
      activity and eliminates hypoxic activation of AMPK in mouse liver.
AB  - Despite the central role of adenosine monophosphate-activated protein kinase
      (AMPK) in the cellular stress response, it is unknown whether age-related changes
      in AMPK activity play a role in the diminished stress tolerance that is
      characteristic of aging. To address this question, we determined in the mouse
      liver how normal aging affects 1) basal AMPK activity, and 2) the degree to which
      AMPK activity is increased by in vivo hypoxia. We found that the basal activity
      of AMPK alpha1, but not alpha2, was higher in livers from 24-month-old mice
      compared to those from 5-month-old mice. Furthermore, while hypoxia elevated AMPK
      alpha1 and alpha2 activities in livers from 5-month-old mice, hypoxia failed to
      increase the activity of either isoform of AMPK in 24-month-old mice. These
      findings suggest that age-associated changes in hepatic AMPK activity may play a
      role in the physiological changes that occur in the liver with normal aging.

PMID- 15741280
TI  - A note on age-related biomarkers.
AB  - Forty-eight randomly selected age-related human biological functions were
      analyzed in order to establish whether or not their (linear) regressions were
      modified by age-related standard errors. Possible reasons for this are advanced.
      Statistically significant multiple regressions were obtained in 25%, and 21% of
      the functions yielded statistically significant changes in the correlations
      between data and age when partial correlation coefficients were calculated. The
      conclusion is that age-related data need to be subjected to the above tests in
      order to minimize confounding factors.

PMID- 15741279
TI  - Effects of long-term caloric restriction on early steps of the insulin-signaling
      system in mouse skeletal muscle.
AB  - In this study, we analyzed the effects of long-term (14 months) caloric
      restriction (CR) on the first steps of the insulin signaling system in skeletal
      muscle of normal mice. CR induced a significant decrease in serum insulin and
      glucose levels, indicating an enhancement of insulin sensitivity. CR reduced the
      in vivo insulin-induced phosphorylation of the insulin receptor substrate (IRS)-1
      by 27%, but this difference was not significant (p =.298). CR reduced insulin
      receptor (IR) abundance by 34% from the ad libitum values, but this difference
      did not reach significance (p =.246). The abundance of the p85 regulatory subunit
      of PI3K and glucose transporter 4 was unaltered after CR. However, IRS-1
      abundance was significantly increased by 42% in muscle of mice exposed to CR.
      These findings indicate that the CR-induced improvement of insulin action in mice
      is not related to changes in glucose transporter 4, the p85 regulatory subunit of
      PI3K, or IR abundance in skeletal muscle but might be related to an increase in
      IRS-1 abundance in this tissue.

PMID- 15741281
TI  - Accumulation of dolichol in older tissues satisfies the proposed criteria to be
      qualified a biomarker of aging.
AB  - Criteria for defining biomarkers have been suggested. Accumulation of dolichol in
      tissues of older animals meets the following criteria: (a) levels of dolichol
      exhibit a quantitative correlation with age in all tissues and are not altered by
      several age-dependent diseases in the same direction as that of aging; (b)
      accumulation is not secondary to metabolic changes of aging and is altered
      appropriately by factors that modulate the aging rate like caloric restriction
      and physical exercise; (c) biomarker is applicable to different tissues across
      mammalian species, including humans, and to trisomy 21 and its hypothalamic
      digoxin-mediated model. Reliable changes in tissue dolichol levels are seen in
      relatively short intervals of time compared to over a life span, and levels can
      be tested on a small amount of tissue without causing death of the animal. In
      this article, we show applications to the study of host-graft interaction and
      detection of gender-related differences in biological age, and we discuss
      mechanism(s) of accumulation.

PMID- 15741282
TI  - Oral administration of melatonin to old ring doves (Streptopelia risoria)
      increases plasma levels of melatonin and heterophil phagocytic activity.
AB  - We analyzed the effect of oral melatonin (23 microg/0.1 ml/animal/d; 1 h before
      dark on 12 consecutive days) in old birds, in natural photoperiods, on the
      hormone's plasma levels, and phagocytosis. Blood collections were performed daily
      at 2:00 am and 4:00 pm until 5 days after the treatment. From day 1, the
      melatonin levels were significantly higher than basal levels at both times.
      Values at 2:00 am were significantly higher than the 4:00 pm values. After
      treatment, the melatonin levels declined, returning from day 14 to basal values
      at both hours. At 2:00 am, phagocytosis was significantly greater than that
      obtained at 4:00 pm and greater than basal values. The 4:00 pm values were only
      significantly greater than basal on days 6 and 8, parallel to a decline in
      superoxide anion levels, which were lowest at 2:00 am. Melatonin administered to
      old ring doves increases the differences between nocturnal and diurnal plasma
      levels, and, in parallel, increases phagocytosis and reduces superoxide radical
      levels in heterophils.

PMID- 15741284
TI  - Maximal aerobic capacity testing of older adults: a critical review.
AB  - Most of the data that describe maximal oxygen uptake (VO(2max)) and the
      requirements for its attainment have been developed using young adults as
      subjects. Many older adults are unable to satisfactorily complete a maximal
      exercise effort in a standard exercise stress test. This review describes
      exercise tests currently available to measure VO(2max) in older adults. PubMed
      and CINAHL databases were searched for studies including healthy individuals
      older than 65 years with reproducible descriptions of the testing protocol. The
      research on VO(2max) testing in healthy individuals older than 65 years is
      limited, does not describe the protocols in detail, and/or lacks information on
      the psychometric properties of the exercise tests. There is a need for refinement
      of the few existing protocols for testing aerobic capacity in older adults, as
      well as the development of new protocols specifically applicable to older adults.
      Consensus on the criteria defining VO(2max) attainment during exercise in older
      adults is required, as well as agreement on the most appropriate exercise
      protocols and equipment, specific to older adults, to successfully fulfil these
      criteria.

PMID- 15741285
TI  - Cross-sectional and longitudinal association between antihypertensive medications
      and cognitive impairment in an elderly population.
AB  - BACKGROUND: The effect of antihypertensive medications on cognitive function has
      not been well studied. The authors' objectives were to investigate the cross
      sectional and longitudinal association between the use of antihypertensive
      medications and cognitive function and to compare different antihypertensive
      medication classes with regard to this association in an elderly population.
      METHODS: The medical records of a convenience sample of patients (n = 993 cross
      sectional and 350 longitudinal; mean age, 76.8 +/- 0.3 years; 74% women; 87%
      White) followed at a geriatric practice were reviewed. Data abstracted included
      demographics, medical history (Alzheimer's disease [AD] or vascular dementia
      [VaD]), use of antihypertensive medications, and results of cognitive assessments
      (the Mini-Mental Status Examination [MMSE] and the Clock Draw Test [CDT]).
      RESULTS: In the cross-sectional analysis, antihypertensive use was not associated
      with MMSE (p >.05), CDT (p >.05), or dementia diagnosis (odds ratio for AD, 0.8;
      95% confidence interval [CI], 0.6 to 1.2; odds ratio for VaD, 1.6; 95% CI, 0.6 to
      4.0). In the longitudinal analysis, antihypertensive use was associated with a
      lower rate of cognitive decline on the MMSE (-0.8 +/- 2 points in users vs -5.8
      +/- 2.5 points in nonusers; p =.007) and on the CDT (-0.3 +/- 0.8 points in users
      vs -2.2 +/- 0.8 points in nonusers; p =.002), and with a lower risk for the
      development of cognitive impairment (odds ratio, 0.56; 95% CI, 0.38 to 0.83; p
      =.004). The trend was similar in patients with baseline AD (p =.02). Patients
      taking diuretics (p =.007), angiotensin-converting enzyme inhibitors (p =.016),
      and beta-blockers (p =.014) had a lower rate of cognitive decline, and patients
      taking angiotensin receptor blockers (p =.016) had improved cognitive scores.
      CONCLUSIONS: Antihypertensive use, particularly diuretics, angiotensin-converting
      enzymes inhibitors, beta-blockers, and angiotensin receptor blockers, may be
      associated with a lower rate of cognitive decline in older adults, including
      those with AD. Until a randomized clinical trial confirms our results, findings
      of this observational study should be interpreted with caution.

PMID- 15741286
TI  - Measures of physical performance and risk for progressive and catastrophic
      disability: results from the Women's Health and Aging Study.
AB  - BACKGROUND: Physical performance measures can predict incident disability, but
      little research has assessed and compared how these measures predict progressive
      and rapid-onset (catastrophic) disability. The authors evaluated the ability of
      upper and lower extremity performance measures to predict progressive and
      catastrophic disability in activities of daily living (ADL), mobility, and upper
      extremity function. METHODS: The incidence of progressive and catastrophic
      disability was assessed semiannually during a 3-year period in 884 women
      participating in the Women's Health and Aging Study I. Four-meter walking speed,
      balance, and chair stands tests were used to evaluate lower extremity function.
      The putting-on-blouse test, the Purdue pegboard test, and grip strength were used
      to assess upper extremity function. Summary performance scores (SPS) for the
      lower and upper extremities were calculated. Among participants in whom
      disability developed, those who reported no difficulty in the previous year were
      defined as cases of catastrophic disability, and those who previously reported
      little or some difficulty were considered to be cases of progressive disability.
      Cox proportional hazard regression analyses were used to evaluate the association
      of performance measures and time to incident disability. The predictive ability
      of performance measures was compared using receiver-operator characteristic
      curves. RESULTS: All lower and upper extremity measures, with the exception of
      grip strength, significantly predicted the onset of progressive ADL disability,
      but only walking speed was significantly associated with the onset of
      catastrophic ADL disability. The chair stands test, walking speed, and the lower
      extremity SPS were significantly associated with the onset of both progressive
      and catastrophic mobility disability. Only lower extremity individual tests and
      SPS significantly predicted the onset of both progressive and catastrophic upper
      extremity disability. The receiver-operator characteristic curves for ADL and
      mobility disability showed that all performance measures evaluated had a greater
      predictive ability for progressive than for catastrophic incident disability.
      This finding was not consistent for upper extremity disability. The areas under
      the curve for walking speed and lower extremity SPS were very similar, ranging
      from 0.58 to 0.81 and from 0.57 to 0.85, and the predictive ability of these two
      measures was the greatest for all disability outcomes assessed. CONCLUSION:
      Physical performance measures of lower extremity and, in particular, walking
      speed and lower extremity SPS are valuable tools to predict different forms of
      disability, especially those with a progressive onset.

PMID- 15741287
TI  - Bone mineral density, soft tissue body composition, strength, and functioning
      after hip fracture.
AB  - BACKGROUND: Although substantial decrements in bone, muscle, and functional
      ability have been reported to follow the occurrence of hip fracture in elderly
      women, little is known about the interrelation of these consequences. The authors
      evaluated the associations among physiologic and functional factors during
      recovery from hip fracture to determine whether any consistent sequence of events
      followed and whether markers of functional outcomes could be identified. METHODS:
      Two hundred five community-dwelling women aged 65 years and older who sustained
      hip fracture between 1992 and 1995 and were admitted to one of two acute care
      hospitals in metropolitan Baltimore, Maryland, participated in a 1-year
      prospective cohort study. Bone mineral density, lean mass, and fat mass were
      measured by dual-energy X-ray absorptiometry during the hospitalization and 2, 6,
      and 12 months later. Functional limitations were self-reported and grip strength
      was measured during interviews at the same time points. Correlation coefficients
      were calculated for all possible pairs of measures and time points. RESULTS:
      Losses of femoral neck bone mineral density and lean body mass and gains in fat
      mass were observed. Grip strength showed early improvement but declined by 1 year
      to levels close to those seen during hospitalization. Functional outcomes showed
      minimal correlation with bone or body composition and only moderate correlation
      with strength. CONCLUSIONS: Physiologic and functional declines follow hip
      fracture in elderly women. These are largely independent of one another and
      suggest that interventions to maximize recovery must simultaneously target
      multiple areas, including bone, muscle, strength, and function.

PMID- 15741288
TI  - Depressive symptoms and development of coronary heart disease events: the Italian
      longitudinal study on aging.
AB  - BACKGROUND: Studies on the association between depressive symptomatology (DS) and
      cardiovascular events and mortality in elderly persons have yielded contradictory
      findings. To address this issue, the authors assessed DS and an extensive array
      of sociodemographic, behavioral, and biological variables in the largest
      population-based sample of older Italians ever studied and analyzed their
      association with coronary heart disease (CHD) morbidity and total number of
      deaths. METHODS: This prospective, community-based cohort study included a sample
      of 5632 Italians, 65 years and older, who were recruited from the demographic
      registries of eight municipalities in Italy. Depressive symptomatology was
      assessed using the Geriatric Depression Scale, and a score > or =10 was used to
      indicate the presence of DS. All traditional cardiovascular disease risk factors
      were assessed at baseline, through questionnaires, blood tests, and physical
      examinations. The outcomes were CHD fatal and nonfatal events and total number of
      deaths. The association of the predictive variables with the outcomes was
      assessed using different Cox models. RESULTS: Baseline DS was associated with a
      higher incidence of fatal and nonfatal CHD events (hazard ratio [HR], 1.66; 95%
      confidence interval [CI], 1.06-2.60) and with cardiovascular mortality in men
      (HR, 2.49; 95% CI, 1.60-3.87) and with total mortality in men (HR, 2.02; 95% CI,
      1.58-2.58) and women (HR, 1.43; 95% CI, 1.04-1.95) at the 4-year follow-up
      assessment. This association was observed after adjusting for a vast array of
      potential confounding variables, including major chronic conditions. CONCLUSIONS:
      Depressive symptomatology confers an increased risk for CHD in men and for total
      mortality in men and women but is not explained by health behaviors, social
      isolation, or biological or clinical determinants.

PMID- 15741289
TI  - A prospective study of the pressure ulcer scale for healing (PUSH).
AB  - BACKGROUND: Although the recently developed Pressure Ulcer Scale for Healing
      (PUSH) was created to monitor healing over time, prospective evidence of its
      validity in measuring healing is lacking. The purpose of this study was to assess
      the validity of PUSH (version 3.0) when used to assess pressure ulcers in
      clinical practice. METHODS: The authors chose a prospective research design using
      a convenience sample of nursing home residents with pressure ulcers. The
      patients' pressure ulcers were assessed each week with the PUSH and the Pressure
      Sore Status Tool. Surface area measurements derived from wound tracings were also
      obtained. Weekly assessments continued until the ulcer healed, the resident died,
      the resident transferred from the nursing home, or 6 months of assessments were
      complete. RESULTS: Thirty-two pressure ulcers comprised the study sample. Twenty
      one (66%) healed during the 6-month study period and 11 (34%) did not heal. The
      PUSH scores decreased significantly over time among the healed ulcers but did not
      among the unhealed ulcers. Similarly, PUSH scores were significantly lower among
      the healed compared with the unhealed ulcers. Finally, total scores on PUSH were
      highly correlated with both the Pressure Sore Status Tool and surface area
      measurements. CONCLUSIONS: The PUSH provides a valid measure of pressure ulcer
      healing over time and accurately differentiates a healing from a nonhealing
      ulcer. It is a clinically practical, evidence-based tool for tracking changes in
      pressure ulcer status when applied at weekly intervals.

PMID- 15741290
TI  - Energy cost and cardiorespiratory adaptation in the "Get-Up-and-Go" test in frail
      elderly women with postural abnormalities and in controls.
AB  - BACKGROUND: This study investigated the hypothesis that postural abnormalities
      might increase energy expenditure during a clinical functional test in frail
      elderly persons. METHODS: Two groups of hospitalized women (aged 73 to 100 years)
      were recruited. Women who showed postural and gait abnormalities as described in
      the psychomotor disadaptation syndrome (PDS) were compared with control
      participants. The authors measured energy expenditure during the timed "up and
      go" test. For each participant, oxygen uptake, carbon dioxide output, expiratory
      minute ventilation, breathing frequency, heart rate, and alveolar ventilation
      were recorded 10 minutes before, during, and 10 minutes after exercise. The
      arterial pressure of carbon dioxide was estimated from expired gases. RESULTS:
      The mean oxygen uptake values were significantly higher in women with PDS than in
      the control group during exercise and recovery periods (4.89 +/- 1.68 vs 3.75 +/-
      1.25 ml . kg(-1) . min(-1) and 4.69 +/- 1.45 vs 3.76 +/- 0.97 ml . kg(-1) . min(
      1), respectively [p <.05]). Expiratory minute ventilation was always higher in
      women with PDS than in controls regardless of the period of the test (p <.05),
      and alveolar ventilation was higher in women with PDS only during the exercise
      period (p <.05). The estimated arterial pressure of carbon dioxide did not change
      significantly between the different phases of the test but was always lower (p
      <.05) in women with PDS compared with the control group. CONCLUSIONS: The
      significant increase in oxygen uptake during the exercise and recovery periods in
      women with PDS compared with controls suggests that postural abnormalities that
      characterize PDS may be associated with an increase in energy expenditure. In
      clinical practice, the low capacity to tolerate even moderate exercise must be
      considered when specific rehabilitation programs are offered to women with PDS.

PMID- 15741291
TI  - Nighttime oxygen desaturation and symptoms of sleep-disordered breathing in long
      stay nursing home residents.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is common in older adults and has
      been implicated as a cause of decreased quality of life and even death. Sparse
      data exist on SDB in the nursing home setting. The authors evaluated SDB (using
      attended nocturnal pulse oximetry) in nursing home residents with daytime
      sleepiness and nighttime sleep disturbance. METHODS: Pulse oximetry was used to
      estimate the prevalence of nighttime oxygen desaturation in 109 long-stay nursing
      home residents (mean [standard deviation] age = 86.2 [9.2] years; 74% women).
      Pulse oximetry findings were compared to a structured observational measurement
      of symptoms of SDB, the Observational Sleep Assessment Instrument. Seventy-one
      participants had concurrent wrist actigraphy to estimate total sleep time during
      oximetry recording. RESULTS: Using the oxygen desaturation index (ODI; average
      number of oxygen desaturations 4% or more below the baseline level per hour), the
      authors found that 40% of the residents had abnormal ODI (ODI more than 5, which
      is suggestive of SDB). Of all observational variables assessed, only loud
      breathing during sleep was significantly correlated with ODI (r =.284; p =.003).
      When ODI was adjusted for estimated total sleep time, higher adjusted ODI was
      associated with higher body mass index (kg/m(2)). CONCLUSIONS: Abnormal ODI is
      common in nursing home residents. Observed loud breathing at night and high body
      mass index may suggest that further assessment of SDB is indicated. Future
      research should determine the importance of SDB and abnormal nocturnal oxygen
      desaturation on functioning and quality of life in nursing home residents.

PMID- 15741292
TI  - Influences of aging on taste perception and oral somatic sensation.
AB  - BACKGROUND: Many elderly persons report reduced taste perception of the foods
      they eat. Any disturbance of taste and oral somatic sensations can induce this
      phenomenon. To determine the cause of decreased taste perception in older
      persons, the authors investigated age-related changes in taste perception and
      somatic sensations in the anterior tongue. METHODS: Thirty healthy young and
      elderly persons participated in this study. Recognition thresholds of four basic
      tastes (sweet, salty, sour, and bitter) and the threshold of irritating sensation
      induced by capsaicin were measured by local stimulation using filter-paper disks.
      Two-point discrimination thresholds were measured to evaluate the spatial acuity
      of touch sensation. All measurements were carried out at the tip of the dorsal
      tongue. RESULTS: The recognition thresholds of all four basic tastes of elderly
      participants were significantly higher than those of young participants. On the
      contrary, age-associated changes were not observed in 2-point discrimination and
      capsaicin sensation. CONCLUSIONS: Significant age-associated deterioration was
      observed in taste but not somatic sensations such as touch and burning pain in
      the tongue, showing that aging affects taste perception and oral somatic
      sensations differently. This suggests that decreased taste perception of foods in
      elderly people may be caused primarily by perceptual loss of taste among oral
      sensations.

PMID- 15741293
TI  - Reliability of a single-session isokinetic and isometric strength measurement
      protocol in older men.
AB  - BACKGROUND: The purposes of the current study were (a) to determine the test
      retest reliability of a single-session isokinetic and isometric strength testing
      protocol in older healthy men, and (b) to compare the outcomes of the reliability
      measures derived from averaged torque scores with those derived from a single
      peak torque score. METHODS: In 19 men (mean age, 72 +/- 5 years), both lower
      limbs were assessed independently on 2 separate test days using the Biodex System
      3 dynamometer. After completing a 5-minute warm-up, each man performed three
      submaximal knee extensions followed by five maximal contractions at 90 degrees /s
      (CON), 0 degrees /s (ISO), and -90 degrees /s (ECC). Average (best 3 of 5) and
      peak CON, ISO, and ECC torque, and CON work and CON power were determined. Peak
      CON work and CON power were recorded from the highest peak torque concentric
      contraction (HPTCC). RESULTS: Intraclass correlation coefficients ranging from
      0.84 to 0.94 were found to have good reliability. The typical error as a
      coefficient of variation ranged from 8% to 10% for averaged measures and from 8%
      to 17% for peak torque and HPTCC. The ratio limits of agreement for average and
      peak CON, ISO, and ECC torque ranged from 23% to 33% and from 40% to 54% for
      average CON and HPTCC work and power. CONCLUSIONS: The test-retest reliability of
      a single-session isokinetic and isometric strength testing protocol in this group
      of older healthy men displayed good relative reliability (intraclass correlation
      coefficient > 0.84); however, because the typical error as a coefficient of
      variation and ratio limits of agreement (absolute reliability) were large, single
      session testing is not recommended.

PMID- 15741294
TI  - Prognostic implications of swallowing ability in elderly patients after initial
      recovery from stroke.
AB  - BACKGROUND: It remains unclear how swallowing assessment can help clinicians to
      predict the risk for pneumonia in elderly persons after ischemic stroke. A
      prospective case-control study was conducted to evaluate the prognostic utility
      of swallowing ability assessments. METHODS: Participants were 136 elderly persons
      who had an acute ischemic stroke 3-12 months previously. They were separated into
      four groups based on their history of repeated episodes of pneumonia in
      combination with swallowing ability: Group 1 had neither repeated pneumonia nor
      swallowing abnormality (n = 69); group 2 had repeated pneumonia but no swallowing
      abnormality (n = 0); group 3 had swallowing abnormality but no repeated pneumonia
      (n = 54); and group 4 had both swallowing abnormality and repeated pneumonia (n =
      13). The follow-up period was as long as 2.2 years. Outcomes and causes of death
      were compared among the groups. RESULTS: During the study, the overall mortality
      rate was higher in group 3 (24 deaths, 44.4%) and group 4 (9 deaths, 69.2%) than
      in group 1 (3 deaths, 4.3%, both p <.05). The annual mortality rate from
      pneumonia was also significantly higher in group 3 (21.2%) and group 4 (38.2%)
      than in group 1 (0.8%, p <.0001). The odds ratio for patients who subsequently
      died of pneumonia was 46.8 between groups 1 and 3. CONCLUSIONS: The high
      sensitivity (.96) and specificity (.68) of swallowing ability indicate that the
      method is useful for identifying those persons at greatest risk for pneumonia and
      death after ischemic stroke.

PMID- 15741295
TI  - Using the FoodEx-LTC to assess institutional food service practices through
      nursing home residents' perspectives on nutrition care.
AB  - Background. Undernutrition occurs in approximately 2 of every 5 nursing home
      residents, negatively influencing their health and quality of life. The purposes
      of this study were to collect data about institutional meal preparation and food
      service practices that promote or retard adequate nutritional intake and to
      evaluate residents' food and food service satisfaction. Methods. The FoodEx-LTC,
      a simple, 44-item, 5-subscale questionnaire that measures food and food service
      satisfaction, was administered to 61 residents. Serum albumin and body mass index
      gauged the nutritional status of each resident. SPSS for Windows, version 10, was
      used for analyses. Results. Overall, 89% of residents were satisfied or somewhat
      satisfied with the food service. Of those who ate in the dining room, 44% had to
      wait to go back to their rooms, presenting a quality of life issue. Fifty-two
      percent received food they hated, 56% often received the same food, and 59%
      received food always cooked the same way. Most residents (75%) felt comfortable
      refusing food they did not like, but 65% did not complain. Most (79%) wanted to
      choose what to eat, but only 54% believed that choosing when to eat was
      important. Conclusions. The FoodEx-LTC, used to monitor nutrition care in nursing
      homes, incorporates residents' views into service delivery and responds to the
      Health Care Finance Administration's Nutritional and Hydration Awareness
      Campaign, part of the federal Nursing Home Initiative. Using the FoodEx-LTC to
      identify residents' perspectives may promote resident satisfaction and dietary
      intake through adaptation of nursing home food and food service practices.

PMID- 15741296
TI  - Patients aged 90 years or older in the intensive care unit.
AB  - BACKGROUND: Age is an important prognostic factor in patients admitted to
      intensive care units (ICUs), but it is not as important as illness severity.
      However, age seems to remain an important independent triage criterion for ICU
      admission, and 90 years of age seems to represent a psychological barrier for
      many ICU physicians. The aim of this preliminary study is to compare the
      management and outcome of patients aged 90 years or older admitted to a
      respiratory ICU with those of patients aged 70 years or younger. METHODS: In our
      matched case-control study over a 6-year period, 36 patients aged 90 years or
      older (case patients) were selected and matched according to sex with 72 controls
      chosen in the 20- to 69-year age range. The Simplified Acute Physiology Score
      (SAPS) II was then computed without using age as a variable. RESULTS: Pre
      existing comorbidities were significantly less frequent in cases than in controls
      (5.1% vs 30.5%, p <.01). Compared to controls, cases were more frequently
      admitted for cardiac failure (22% vs 7%, p <.05) and less frequently for
      neurological diseases (0% vs 11%, p <.05). The use of advanced life-support
      measures in the ICU such as mechanical ventilation, central venous or arterial
      catheterization, and vasoactive and/or inotropic drugs was not significantly
      different between case patients and controls. This was also the case for ICU
      mortality and for the mean duration of ICU and hospital stay. Although there was
      a trend toward a higher hospital mortality among case patients than among
      controls, it did not reach statistical significance (47% vs 27%, p =.07).
      CONCLUSION: Our results reinforce the idea that age alone is not a relevant
      criterion for ICU admission.

PMID- 15741297
TI  - Rapid neurological decline and death in a 79-year-old woman.

PMID- 15741298
TI  - Insulin resistance and cognitive aging in long-lived and short-lived mice.

PMID- 15741299
TI  - Radiation treatment for medulloblastoma: a review of 64 cases at a single
      institute.
AB  - BACKGROUND: Although the optimal treatment mode for medulloblastoma is frequently
      discussed, results based on large series of cases, especially those treated in
      Asia, have rarely been reported. Our purpose was to evaluate the efficacy of
      postoperative radiation therapy, and to identify prognostic factors, in a
      relatively large cohort of patients with limited-stage medulloblastoma treated at
      a single institute in China. METHODS: Between January 1996 and April 2001, 69
      patients with Chang stage M0/M1 medulloblastoma were referred to our hospital for
      radiation therapy after total or subtotal resection of the primary tumor. All
      patients received 30 Gy to the craniospinal axis followed by a 20-25 Gy boost to
      the posterior fossa (median fraction, 1.8 Gy). RESULTS: Sixty-four patients were
      followed for a median period of 38.5 months. The rates of 3-year and 5-year
      overall survival were 68.8% and 55.7%, respectively; corresponding disease-free
      survival were 57.8% and 51.4%, respectively. Patients who had received radiation
      treatment within 25 days after resection had a greater probability of 3-year
      survival (81.5% versus 59.5%; P = 0.11) and 3-year disease-free survival (74.1%
      versus 46.0%; P = 0.03) than patients who began radiation treatment later. No
      relationship was found between survival and age, sex or tumor size. CONCLUSIONS:
      This regimen was comparatively ineffective in preventing recurrence of
      postoperative medulloblastoma; however, we found that the interval between
      surgery and radiation is a significant prognostic factor for disease-free
      survival.

PMID- 15741300
TI  - Hyperfractionated radiation therapy for locoregionally advanced nasopharyngeal
      cancer.
AB  - OBJECTIVE: The purpose of this study is to clarify the efficacy and toxicity of
      hyperfractionated radiation therapy (RT) for patients with nasopharyngeal cancer
      (NPC). METHODS: Twenty-two patients with NPC treated at our hospital between
      April 1994 and December 2002 were the subjects of this study. They received
      hyperfractionated RT with a fraction size of 1.2 Gy, with a median tumor dose of
      72 Gy (range 64.8-80.4). During this study period, our institutional strategy for
      locoregionally advanced NPC included neoadjuvant or concurrent chemotherapy
      combined with hyperfractionated RT, and 17 patients received some forms of
      cisplatin-containing chemotherapy. RESULTS: With a median follow-up of 59 months,
      the estimated 5-year disease-free survival rate and overall survival rate were
      72.7 and 85.2%, respectively. Acute hematological toxicities were acceptable and
      manageable. However, >50% of patients required nutritional support, and
      experienced severe pharyngitis, skin reaction and body weight loss. With regard
      to late sequelae, one patient developed grade 3 osteomyelitis, and one patient
      each developed grade 4 passage disturbance and laryngeal edema. No patients
      experienced any grades of optic nerve injury or temporal lobe necrosis.
      CONCLUSIONS: Hyperfractionated RT using 1.2 Gy per fraction, for a total dose of
      72 Gy, produces a comparable treatment outcome. Although deleterious neurological
      sequelae were not observed in this study, caution should be exercised regarding
      other late sequelae, such as osteomyelitis and passage disturbance.

PMID- 15741301
TI  - Inverse correlation between the expression of O6-methylguanine-DNA methyl
      transferase (MGMT) and p53 in breast cancer.
AB  - BACKGROUND: Expression of O(6)-methylguanine-DNA methyl transferase (MGMT), a DNA
      repair protein, has been associated with tumor resistance to alkylating agents
      such as cyclophosphamide. Promoter hypermethylation of MGMT is a strong predictor
      of survival, and expression of mutant p53 protein may be associated with
      downregulated MGMT expression in brain tumors. In order to clarify further the
      correlation between MGMT and p53 expression, we investigated the expression
      levels of both MGMT and p53 in breast cancer. METHODS: MGMT and p53 expression
      was examined in tissues from 48 consecutive cases of primary breast cancer
      patients using immunohistochemical staining with antibodies specific for MGMT and
      p53. The prognosis for survival was analyzed based on MGMT and p53
      immunoreactivity and clinicopathological characteristics. RESULTS: Expression of
      either MGMT or p53 was classified as negative or positive based on
      immunohistochemical staining. The expression of MGMT showed a significant inverse
      correlation with three clinicopathological characteristics, the status of the
      estrogen receptor, local recurrence and distant metastasis. There was a
      significant correlation between the expression level of p53 and the lymphatic
      involvement, estrogen receptor status and distant metastasis. MGMT and p53 were
      correlated with distant metastasis and local recurrence, but Kaplan-Meier curves
      did not show a significant difference. MGMT immuno-negative specimens showed a
      significantly higher expression of p53 (P = 0.026, chi(2) test). CONCLUSION: p53
      may be associated with the regulation of MGMT expression in breast cancers.

PMID- 15741302
TI  - Treatment results and prognostic factors of early breast cancer treated with a
      breast conserving operation and radiotherapy.
AB  - BACKGROUND: The purpose of this study was to analyze the prognostic factors
      affecting local control and survival rates for patients with early breast cancer
      who received breast conserving treatment (BCT) and to find out the optimal
      treatment according to their risk factors. METHODS: From October 1994 to December
      2001, 605 patients with 611 stage I and II breast cancers received BCT, and the
      results were analyzed retrospectively. BCT consists of breast conserving surgery
      and whole breast irradiation. All the patients underwent lumpectomy or
      quadrantectomy. Axillary lymph node dissection or sentinel lymph node biopsy was
      performed in 608 cases (99.5%). The radiation dose to the whole breast was 50.4
      Gy over 5 weeks with a 1.8 Gy daily fraction and with boost doses of 9-14.4 Gy
      administered to the tumor bed. Adjuvant chemotherapy was performed in most of the
      patients with axillary lymph node metastasis or tumors larger than 1 cm. The
      median follow-up period was 47 months. RESULTS: Local relapse, regional relapse
      and distant metastasis occurred in 15 (2.5%), 16 (2.6%) and 43 patients (7.1%),
      respectively. The 5-year overall survival, local-relapse-free survival, distant
      metastasis-free survival and disease-free survival rates were 95.3%, 97.2%, 91.3%
      and 88.5%, respectively. On multivariate analysis, age (P = 0.02), number of
      involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.01) affected
      the local-relapse-free survival. The factors associated with disease-free
      survival were the T stage (P = 0.05), number of involved axillary lymph nodes (P
      = 0.01) and nuclear grade (P = 0.001). Overall survival was associated with the T
      stage (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and c-erb B2
      overexpression (P = 0.05). Patients with more than two factors among (i) age
      </=35 years, (ii) positive lymph node metastasis and (iii) high nuclear grade
      showed a poor 5-year local-relapse-free survival rate compared with others (P =
      0.001). Also, patients with more than two factors among (i) tumor size >1 cm,
      (ii) positive lymph node metastasis and (iii) high nuclear grade showed an
      inferior 5-year disease-free survival rate compared with others (P = 0.0005).
      CONCLUSIONS: The most important prognostic factor affecting local control,
      disease-free survival and overall survival was axillary lymph node metastasis.
      The nuclear grade influenced local control and disease relapse. Patients with
      multiple unfavorable risk factors such as positive axillary lymph nodes, high
      nuclear grade, young age and large tumor showed poorer local control and disease
      free survival than patients without any risk factors, and so more aggressive
      treatment is required for these patients.

PMID- 15741303
TI  - Surgical significance of superficial cancer spread in early gallbladder cancer.
AB  - BACKGROUND: A considerable percentage of gallbladder cancers are accompanied by
      superficial cancer spread adjacent to the main tumor, therefore cholecystectomy
      for early gallbladder cancer must be performed carefully to avoid leaving cancer
      cells at the surgical margins. METHODS: Thirty-two patients with gallbladder
      cancer invading no more than perimuscular connective tissue underwent surgical
      resection at our medical center. After the operation, resected specimens were
      investigated macroscopically and microscopically to clarify the
      clinicopathological features and the risk factors of superficial cancer spread.
      RESULTS: Sixty-six percent of all cases (21 cases) had superficial cancer spread.
      Comparison between the cases having superficial cancer spread and the cases
      without it revealed that the macroscopic morphology of the primary tumor and the
      depth of cancer invasion in the gallbladder wall were significantly different
      between the two groups. Furthermore, multivariate analysis indicated that
      'superficial raised type' in macroscopic morphology was an independent predictive
      factor for having superficial cancer spread. Superficial cancer spread from the
      main tumor located in the neck of the gallbladder grows predominantly in the
      direction of the fundus. More advanced gallbladder cases were accompanied by more
      extensive superficial spread. CONCLUSIONS: Superficial cancer spread is
      frequently observed adjacent to the gallbladder cancer, especially in the
      superficial raised type. A negative margin should be confirmed by intraoperative
      frozen section histology while performing cholecystectomy.

PMID- 15741304
TI  - Radiotherapy for uterine cervical cancer: results of the 1995-1997 patterns of
      care process survey in Japan.
AB  - OBJECTIVE: The aim of this study is to establish Japanese national practice
      patterns for uterine cervical cancer patients who received radiotherapy without
      surgery. METHODS: The Japanese Patterns of Care Study (JPCS) conducted a national
      survey of 73 institutions using two-stage cluster sampling, and collected
      specific information on 591 patients with uterine cervical cancer treated by
      radiotherapy without planned surgery between 1995 and 1997. RESULTS: The median
      age of the patients was 70 years. Karnofsky performance status (KPS) was >/=90
      for 37%. Most patients (95%) had histology of squamous cell carcinoma. Ten
      percent were stage I, 29% stage II, 48% stage III and 13% stage IVA. Photon beams
      of 10-14 MV were the most used for external beam radiotherapy (EBRT). The beam
      energy utilized varied significantly by institution strata. Midline block was
      used in approximately 70% of institutions. Intracavitary brachytherapy (ICBT) was
      performed in 77%. Institution strata correlated significantly with the ICBT
      application. The majority of patients (89%) were treated with high-dose-rate
      (HDR) ICBT. The median single point A dose of HDR-ICBT was 600 cGy. The median
      summated point A dose from EBRT and HDR-ICBT was 5800 cGy (range: 1196-8600). The
      median overall treatment time including ICBT was 49 days. Twenty-four percent of
      the patients received chemotherapy. Concurrent chemoradiation was performed in
      5%. CONCLUSIONS: The JPCS established the Japanese national practice patterns of
      care for uterine cervical cancer patients treated with radiotherapy without
      planned surgery between 1995 and 1997. This survey demonstrated that the
      institutional strata significantly affected several practice patterns.

PMID- 15741305
TI  - MRI accurately depicts underlying DCIS in a patient with Paget's disease of the
      breast without palpable mass and mammography findings.
AB  - Breast-conserving therapy must be carefully indicated among patients with Paget's
      disease of the breast, because the disease is often associated with an underlying
      in situ or invasive carcinoma, even when there are no palpable mass or
      mammography findings. We report a 52-year-old woman who complained of skin color
      change of her right nipple for 11 months. No mass was palpable in her breasts,
      and mammography did not show any density or calcification. Nipple biopsy revealed
      Paget's disease of the breast with ductal carcinoma in situ (DCIS) in the breast
      epithelium just beneath the nipple. Magnetic resonance imaging (MRI) of the
      breast demonstrated diffuse segmental enhancement in two different quadrants.
      According to the pattern of enhancement, the lesions depicted by MRI were
      diagnosed as an extensively spreading type of DCIS. Based on informed consent,
      the patient received a total mastectomy. The histopathological examination
      demonstrated non-invasive ductal carcinoma with comedo-necrosis. The histological
      mapping with subserial sectioning demonstrated an extent of the lesions that
      corresponded accurately to the lesions defined by MRI. We conclude that MRI may
      play an important role in selecting candidates for breast-conserving therapy out
      of those patients with mammary Paget's disease with no clinical evidence of an
      underlying breast carcinoma.

PMID- 15741306
TI  - Endometrioid adenocarcinoma arising from endometriosis of the mesenterium of the
      sigmoid colon.
AB  - This report presents a case of endometrioid adenocarcinoma arising from
      endometriosis of the mesenterium of the sigmoid colon following total abdominal
      hysterectomy and bilateral salpingo-oophorectomy for leiomyoma of the uterus and
      infiltrating pelvic endometriosis, and hormone replacement therapy. A 62-year-old
      woman presented with an abdominal tumor. Based on the diagnosis of mesocolonic
      tumor, sigmoidectomy with lymph node resection was performed. The tumor cells
      were immunopositive for cytokeratin 7, but negative for cytokeratin 20, and the
      tumor was histologically diagnosed as endometrioid adenocarcinoma of the
      mesocolon. Hyperestrogenism has been implicated as a risk factor for the
      development of cancer from endometriosis. The patient had been receiving high
      dose unopposed estrogens for 14 years after a total abdominal hysterectomy and
      bilateral salpingo-oophorectomy. Physicians should recognize that endometriosis
      associated neoplasms are able to cause symptoms or signs such as abdominal and/or
      pelvic pain, pelvic mass, and vaginal bleeding, especially if the patient has
      been treated with hormone replacement therapy. It is important to recognize the
      possibility of tumors arising from endometriosis when evaluating intestinal or
      mesenteric neoplasms in women, even in the patient who has previously undergone
      total abdominal hysterectomy and bilateral salpingo-oophorectomy, particularly if
      the patient has a history of endometriosis and has received hormone replacement
      therapy.

PMID- 15741307
TI  - Association of a genetic polymorphism of the E-cadherin gene with prostate cancer
      in a Japanese population.
AB  - The E-cadherin gene has been identified as having a physiological role in
      cellular attachment, and is hypothesized to participate in carcinogenesis. A
      polymorphism (an A to C substitution) in the 5'-untranslated region has a direct
      effect on E-cadherin gene transcriptional regulation. We explored the association
      between E-cadherin gene polymorphism and the risk of prostate cancer in a
      Japanese population. The subjects consisted of 236 patients with prostate cancer,
      209 benign prostatic hyperplasia (BPH) patients and 139 male controls. A
      marginally significant difference was found between prostate cancer patients and
      male controls (P = 0.053). No significant difference was observed between
      prostate cancer and BPH patients. When patients with prostate cancer were divided
      into two groups, stage A+B and stage C+D, a significant difference was observed
      between progressive cancer patients (stage C+D) and male controls (odds ratio =
      1.93, P = 0.016). It is possible that the presence of one A allele resulted in an
      increased risk of cancer progression.

PMID- 15741309
TI  - An overseas perspective of evolving gastric cancer practices in Japan.

PMID- 15741310
TI  - Comparison of cancer mortality (lung cancer) in five countries: France, Italy,
      Japan, UK and USA from the WHO Mortality Database (1960-2000).

PMID- 15741311
TI  - Integrating global proteomic and genomic expression profiles generated from islet
      alpha cells: opportunities and challenges to deriving reliable biological
      inferences.
AB  - Systematic profiling of expressed gene products represents a promising research
      strategy for elucidating the molecular phenotypes of islet cells. To this end, we
      have combined complementary genomic and proteomic methods to better assess the
      molecular composition of murine pancreatic islet glucagon-producing alphaTC-1
      cells as a model system, with the expectation of bypassing limitations inherent
      to either technology alone. Gene expression was measured with an Affymetrix
      MG_U74Av2 oligonucleotide array, while protein expression was examined by
      performing high-resolution gel-free shotgun MS/MS on a nuclear-enriched cell
      extract. Both analyses were carried out in triplicate to control for experimental
      variability. Using a stringent detection p value cutoff of 0.04, 48% of all
      potential mRNA transcripts were predicted to be expressed (probes classified as
      present in at least two of three replicates), while 1,651 proteins were
      identified with high-confidence using rigorous database searching. Although 762
      of 888 cross-referenced cognate mRNA-protein pairs were jointly detected by both
      platforms, a sizeable number (126) of gene products was detected exclusively by
      MS alone. Conversely, marginal protein identifications often had convincing
      microarray support. Based on these findings, we present an operational framework
      for both interpreting and integrating dual genomic and proteomic datasets so as
      to obtain a more reliable perspective into islet alpha cell function.

PMID- 15741312
TI  - Statistical and computational methods for comparative proteomic profiling using
      liquid chromatography-tandem mass spectrometry.
AB  - The combined method of LC-MS/MS is increasingly being used to explore differences
      in the proteomic composition of complex biological systems. The reliability and
      utility of such comparative protein expression profiling studies is critically
      dependent on an accurate and rigorous assessment of quantitative changes in the
      relative abundance of the myriad of proteins typically present in a biological
      sample such as blood or tissue. In this review, we provide an overview of key
      statistical and computational issues relevant to bottom-up shotgun global
      proteomic analysis, with an emphasis on methods that can be applied to improve
      the dependability of biological inferences drawn from large proteomic datasets.
      Focusing on a start-to-finish approach, we address the following topics: 1) low
      level data processing steps, such as formation of a data matrix, filtering, and
      baseline subtraction to minimize noise, 2) mid-level processing steps, such as
      data normalization, alignment in time, peak detection, peak quantification, peak
      matching, and error models, to facilitate profile comparisons; and, 3) high-level
      processing steps such as sample classification and biomarker discovery, and
      related topics such as significance testing, multiple testing, and choice of
      feature space. We report on approaches that have recently been developed for
      these steps, discussing their merits and limitations, and propose areas deserving
      of further research.

PMID- 15741313
TI  - Transcriptional silencing of a transgene by RNAi in the soma of C. elegans.
AB  - The silencing of transgene expression at the level of transcription in the soma
      of Caenorhabditis elegans through an RNAi-dependent pathway has not been
      previously characterized. Most gene silencing due to RNAi in C. elegans occurs at
      the post-transcriptional level. We observed transcriptional silencing when worms
      containing the elt-2::gfp/LacZ transgene were fed RNA produced from the commonly
      used L4440 vector. The transgene and the vector share plasmid backbone sequences.
      This transgene silencing depends on multiple RNAi pathway genes, including dcr-1,
      rde-1, rde-4, and rrf-1. Unlike post-transcriptional gene silencing in worms, elt
      2::gfp/LacZ silencing is dependent on the PAZ-PIWI protein Alg-1 and on the HP1
      homolog Hpl-2. The latter is a chromatin silencing factor, and expression of the
      transgene is inhibited at the level of intron-containing precursor mRNA. This
      inhibition is accompanied by a decrease in the acetylation of histones associated
      with the transgene. This transcriptional silencing in the soma can be
      distinguished from transgene silencing in the germline by its inability to be
      transmitted across generations and its dependence on the rde-1 gene. We therefore
      define this type of silencing as RNAi-induced Transcriptional Gene Silencing
      (RNAi-TGS). Additional chromatin-modifying components affecting RNAi-TGS were
      identified in a candidate RNAi screen.

PMID- 15741314
TI  - Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint
      control.
AB  - The role of protein arginine methylation in the DNA damage checkpoint response
      and DNA repair is largely unknown. Herein we show that the MRE11 checkpoint
      protein is arginine methylated by PRMT1. Mutation of the arginines within MRE11
      severely impaired the exonuclease activity of MRE11 but did not influence its
      ability to form complexes with RAD50 and NBS1. Cells containing hypomethylated
      MRE11 displayed intra-S-phase DNA damage checkpoint defects that were
      significantly rescued with the MRE11-RAD50-NBS1 complex. Our results suggest that
      arginine methylation regulates the activity of MRE11-RAD50-NBS1 complex during
      the intra-S-phase DNA damage checkpoint response.

PMID- 15741315
TI  - Intergenic transcription through a polycomb group response element counteracts
      silencing.
AB  - Polycomb group response elements (PREs) mediate the mitotic inheritance of gene
      expression programs and thus maintain determined cell fates. By default, PREs
      silence associated genes via the targeting of Polycomb group (PcG) complexes.
      Upon an activating signal, however, PREs recruit counteracting trithorax group
      (trxG) proteins, which in turn maintain target genes in a transcriptionally
      active state. Using a transgenic reporter system, we show that the switch from
      the silenced to the activated state of a PRE requires noncoding transcription.
      Continuous transcription through the PRE induced by an actin promoter prevents
      the establishment of PcG-mediated silencing. The maintenance of epigenetic
      activation requires transcription through the PRE to proceed at least until
      embryogenesis is completed. At the homeotic bithorax complex of Drosophila,
      intergenic PRE transcripts can be detected not only during embryogenesis, but
      also at late larval stages, suggesting that transcription through endogenous PREs
      is required continuously as an anti-silencing mechanism to prevent the access of
      repressive PcG complexes to the chromatin. Furthermore, all other PREs outside
      the homeotic complex we tested were found to be transcribed in the same tissue as
      the mRNA of the corresponding target gene, suggesting that anti-silencing by
      transcription is a fundamental aspect of the cellular memory system.

PMID- 15741316
TI  - Perspective: machines for RNAi.
AB  - RNA silencing pathways convert the sequence information in long RNA, typically
      double-stranded RNA, into approximately 21-nt RNA signaling molecules such as
      small interfering RNAs (siRNAs) and microRNAs (miRNAs). siRNAs and miRNAs provide
      specificity to protein effector complexes that repress mRNA transcription or
      translation, or catalyze mRNA destruction. Here, we review our current
      understanding of how small RNAs are produced, how they are loaded into protein
      complexes, and how they repress gene expression.

PMID- 15741317
TI  - Inactivation of TGFbeta signaling in neural crest stem cells leads to multiple
      defects reminiscent of DiGeorge syndrome.
AB  - Specific inactivation of TGFbeta signaling in neural crest stem cells (NCSCs)
      results in cardiovascular defects and thymic, parathyroid, and craniofacial
      anomalies. All these malformations characterize DiGeorge syndrome, the most
      common microdeletion syndrome in humans. Consistent with a role of TGFbeta in
      promoting non-neural lineages in NCSCs, mutant neural crest cells migrate into
      the pharyngeal apparatus but are unable to acquire non-neural cell fates.
      Moreover, in neural crest cells, TGFbeta signaling is both sufficient and
      required for phosphorylation of CrkL, a signal adaptor protein implicated in the
      development of DiGeorge syndrome. Thus, TGFbeta signal modulation in neural crest
      differentiation might play a crucial role in the etiology of DiGeorge syndrome.

PMID- 15741318
TI  - Mammalian polycomb-mediated repression of Hox genes requires the essential
      spliceosomal protein Sf3b1.
AB  - Polycomb group (PcG) proteins are responsible for the stable repression of
      homeotic (Hox) genes by forming multimeric protein complexes. We show (1)
      physical interaction between components of the U2 small nuclear ribonucleoprotein
      particle (U2 snRNP), including Sf3b1 and PcG proteins Zfp144 and Rnf2; and (2)
      that Sf3b1 heterozygous mice exhibit skeletal transformations concomitant with
      ectopic Hox expressions. These alterations are enhanced by Zfp144 mutation but
      repressed by Mll mutation (a trithorax-group gene). Importantly, the levels of
      Sf3b1 in PcG complexes were decreased in Sf3b1-heterozygous embryos. These
      findings suggest that Sf3b1-PcG protein interaction is essential for true PcG
      mediated repression of Hox genes.

PMID- 15741319
TI  - Members of the heat-shock protein 70 family promote cancer cell growth by
      distinct mechanisms.
AB  - Whereas the stress-inducible heat-shock protein 70 (Hsp70) has gained plenty of
      attention as a putative target for tumor therapy, little is known about the role
      of other Hsp70 proteins in cancer. Here we present the first thorough analysis of
      the expression and function of the cytosolic Hsp70 proteins in human cancer cells
      and identify Hsp70-2, a protein essential for spermatogenesis, as an important
      regulator of cancer cell growth. Targeted knock-down of the individual family
      members by RNA interference revealed that both Hsp70 and Hsp70-2 were required
      for cancer cell growth, whereas the survival of tumorigenic as well as
      nontumorigenic cells depended on Hsc70. Cancer cells depleted for Hsp70 and Hsp70
      2 displayed strikingly different morphologies (detached and round vs. flat
      senescent-like), cell cycle distributions (G2/M vs. G1 arrest) and gene
      expression profiles. Only Hsp70-2 depletion induced the expression of macrophage
      inhibitory cytokine-1 that was identified as a target of P53 tumor-suppressor
      protein and a mediator of the G1 arrest and the senescent phenotype. Importantly,
      concomitant depletion of Hsp70 and Hsp70-2 had a synergistic antiproliferative
      effect on cancer cells. Thus, highly homologous Hsp70 proteins bring about
      nonoverlapping functions essential for cell growth and survival.

PMID- 15741320
TI  - HFR1 is targeted by COP1 E3 ligase for post-translational proteolysis during
      phytochrome A signaling.
AB  - Upon activation by far-red light, phytochrome A signals are transduced through
      several pathways to promote photomorphogenesis. The COP1 E3 ligase represses
      photomorphogenesis in part by targeting transcription activators such as LAF1 and
      HY5 for destruction. Another positive regulator of photomorphogenesis is HFR1, a
      basic helix-loop-helix (bHLH) transcription factor. Here, we show that HFR1
      colocalizes with COP1 in nuclear bodies, and that the HFR1 N-terminal region
      (amino acids 1-131) interacts with the COP1 WD40 domain. HFR1(DeltaN), an HFR1
      mutant lacking the two N-terminal, COP1-interacting motifs, still localizes in
      nuclear bodies and retains weak affinity for COP1. Both HFR1 and HFR1(DeltaN) can
      be ubiquitinated by COP1, although with different efficiencies. Expression of 35S
      HFR1(DeltaN) in wild-type plants confers greater hypersensitivity to FR than 35S
      HFR1 expression, and only seedlings expressing 35S-HFR1(DeltaN) display
      constitutive photomorphogenesis. These phenotypic differences can be attributed
      to the instability of HFR1 compared with HFR1(DeltaN). In transgenic plants, HFR1
      levels are significantly elevated upon induced expression of a dominant-negative
      COP1 mutant that interferes with endogenous COP1 E3 activity. Moreover, induced
      expression of wild-type COP1 in transgenic plants accelerates post-translational
      degradation of HFR1 under FR light. Taken together, our results show that HFR1 is
      ubiquitinated by COP1 E3 ligase and marked for post-translational degradation
      during photomorphogenesis.

PMID- 15741321
TI  - FGF8 initiates inner ear induction in chick and mouse.
AB  - In both chick and mouse, the otic placode, the rudiment of the inner ear, is
      induced by at least two signals, one from the cephalic paraxial mesoderm and the
      other from the neural ectoderm. In chick, the mesodermal signal, FGF19, induces
      neural ectoderm to express additional signals, including WNT8c and FGF3,
      resulting in induction of the otic placode. In mouse, mesodermal Fgf10 acting
      redundantly with neural Fgf3 is required for induction of the placode. To
      determine how the mesodermal inducers of the otic placode are localized, we took
      advantage of the unique strengths of the two model organisms. We show that
      endoderm is necessary for otic induction in the chick and that Fgf8, expressed in
      the chick endoderm subjacent to Fgf19, is both sufficient and necessary for the
      expression of Fgf19 in the mesoderm. In the mouse, Fgf8 is also expressed in
      endoderm as well as in other germ layers in the periotic placode region. We show
      that otic induction fails in embryos null for Fgf3 and hypomorphic for Fgf8 and
      expression of mesodermal Fgf10 is reduced. Thus, Fgf8 plays a critical upstream
      role in an FGF signaling cascade required for otic induction in chick and mouse.

PMID- 15741324
TI  - Improving the health and safety of children in nonparental early education and
      child care.

PMID- 15741322
TI  - Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs
      the functionality of the forebrain clock and affects nociception.
AB  - The orphan nuclear receptor Ear2 (Nr2f6) is transiently expressed in the rostral
      part of the rhombic lip in which the locus coeruleus (LC) arises. LC development,
      regulated by a signaling cascade (Mash1 --> Phox2b --> Phox2a), is disrupted in
      Ear2-/- embryos as revealed by an approximately threefold reduction in the number
      of Phox2a- and Phox2b-expressing LC progenitor cells. Mash1 expression in the
      rhombic lip, however, is unaffected, placing Ear2 in between Mash1 and Phox2a/b.
      Dopamine-beta-hydroxylase and tyrosine hydroxylase staining demonstrate that >70%
      of LC neurons are absent in the adult with agenesis affecting primarily the
      dorsal division of the LC. Normally, this division projects noradrenergic
      efferents to the cortex that appear to be diminished in Ear2-/- since the
      cortical concentration of noradrenaline is four times lower in these mice. The
      rostral region of the cortex is known to contain a circadian pacemaker regulating
      adaptability to light- and restricted food-driven entrainment. In situ
      hybridization establishes that the circadian expression pattern of the clock gene
      Period1 is abolished in the Ear2-/- forebrain. Behavioral experiments reveal that
      Ear2 mutants have a delayed entrainment to shifted light-dark cycles and adapt
      less efficiently to daytime feeding schedules. We propose that neurons in the
      dorsal division of LC contribute to the regulation of the forebrain clock, at
      least in part, through targeted release of noradrenaline into the cortical area.

PMID- 15741325
TI  - Consultation with the specialist: childhood leukemia.

PMID- 15741326
TI  - Index of suspicion.

PMID- 15741323
TI  - A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural
      tube.
AB  - During development, many signaling factors behave as morphogens, long-range
      signals eliciting different cellular responses according to their concentration.
      In ventral regions of the spinal cord, Sonic Hedgehog (Shh) is such a signal and
      controls the emergence, in precise spatial order, of distinct neuronal subtypes.
      The Gli family of transcription factors plays a central role in this process.
      Here we demonstrate that a gradient of Gli activity is sufficient to mediate,
      cell-autonomously, the full range of Shh responses in the neural tube. The
      incremental two- to threefold changes in Shh concentration, which determine
      alternative neuronal subtypes, are mimicked by similar small changes in the level
      of Gli activity, indicating that a gradient of Gli activity represents the
      intracellular correlate of graded Shh signaling. Moreover, our analysis suggests
      that cells integrate the level of signaling over time, consistent with the idea
      that signal duration, in addition to signal strength, is an important parameter
      controlling dorsal-ventral patterning. Together, these data indicate that Shh
      signaling is transduced, without amplification, into a gradient of Gli activity
      that orchestrates patterning of the ventral neural tube.

PMID- 15741327
TI  - Rapid formation of amyloid from alpha-monomeric recombinant human PrP in vitro.
AB  - The infectious agent of prion diseases is identified with PrP(Sc), a beta-rich,
      amyloidogenic and partially protease resistant isoform of the cellular
      glycoprotein, PrP(C). To understand the process of prion formation in vivo, we
      and others have studied defined misfolding pathways of recombinant PrP in vitro.
      The low-level infectivity of the in vitro misfolded murine PrP amyloid has
      recently been reported. Here we analyze the in vitro kinetics of amyloid
      formation from recombinant human PrP(90-231) in vitro in the context of two
      common allelic forms of PrP found in human populations that are associated with
      differences in prion disease susceptibility and pathological phenotype. We show
      that human PrP amyloid forms readily from its PrP(C)-like state in vitro, that
      the lag time of the reaction can be further shortened by the presence of a "seed"
      of pre-formed PrP amyloid, and that amyloid propagation is more complex than a
      simple crystallization process. We further show that the kinetics of amyloid
      formation do not differ between the Met129 and Val129 allelomorphs of human PrP,
      and that amyloid from each functions as an equally effective seed in
      heterologous, as in homologous amyloid reactions. The results could illuminate
      the process of amyloid formation in vivo as well as help understanding prion
      pathogenesis.

PMID- 15741328
TI  - Extraordinarily stable disulfide-linked homodimer of human growth hormone.
AB  - Although a 22-kDa human growth hormone (hGH) is the predicted protein product of
      the hGH-N gene, a pleiotropic collection of uncharacterized molecular weight and
      charge isoforms is also produced. Using chromatography and preparative SDS-PAGE
      under reducing conditions we isolated an unusually stable mercaptoethanol
      resistant (MER) 45-kDa hGH. A 5-h incubation at 100 degrees C in the presence of
      2-mercaptoethanol was required to convert approximately 90% of MER-45-kDa hGH
      into a 22-kDa hGH. Other reductants were not as effective in splitting MER-45-kDa
      hGH. After fracturing MER-45-kDa hGH, the 22-kDa hGH fragments would
      spontaneously reassociate if the reductant was removed; however, alkylation of
      cysteine residues prevented their reassociation. Identical amino acid sequences
      for the first six N-terminal residues were obtained for MER-45-kDa hGH and its 22
      kDa hGH cleavage product. Structural identity of MER-45-kDa hGH and 22-kDa hGH
      was demonstrated by MALDI-TOF mass spectrometry of tryptic digests. MER-45-kDa
      hGH did not break up upon incubation with EDTA and EGTA. The significance of this
      work to our understanding of the structure of hGH isoforms is that it
      demonstrates that MER-45-kDa hGH is not a single chain polypeptide but is instead
      a homodimer of 22-kDa hGH monomers. The MER-45-kDa hGH dimer is held together by
      interchain disulfide bonds and not by divalent metal cation bridges.
      Additionally, MER-45-kDa hGH's interchain disulfide links are exceptionally
      resistant to reducing agents and thus confer extreme stability to the homodimer.

PMID- 15741329
TI  - ATP specifically drives refolding of non-native conformations of cytochrome c.
AB  - An increasing body of evidence ascribes to misfolded forms of cytochrome c (cyt
      c) a role in pathophysiological events such as apoptosis and disease. Here, we
      examine the conformational changes induced by lipid binding to horse heart cyt c
      at pH 7 and study the ability of ATP (and other nucleotides) to refold several
      forms of unfolded cyt c such as oleic acid-bound cyt c, nicked cyt c, and acid
      denatured cyt c. The CD and fluorescence spectra demonstrate that cyt c unfolded
      by oleic acid has an intact secondary structure, and a disrupted tertiary
      structure and heme environment. Furthermore, evidence from the Soret CD,
      electronic absorption, and resonance Raman spectra indicates the presence of an
      equilibrium of at least two low-spin species having distinct heme-iron(III)
      coordination. As a whole, the data indicate that binding of cyt c to oleic acid
      leads to a partially unfolded conformation of the protein, resembling that
      typical of the molten globule state. Interestingly, the native conformation is
      almost fully recovered in the presence of ATP or dATP, while other nucleotides,
      such as GTP, are ineffective. Molecular modeling of ATP binding to cyt c and
      mutagenesis experiments show the interactions of phosphate groups with Lys88 and
      Arg91, with adenosine ring interaction with Glu62 explaining the unfavorable
      binding of GTP. The finding that ATP and dATP are unique among the nucleotides in
      being able to turn non-native states of cyt c back to native conformation is
      discussed in the light of cyt c involvement in cell apoptosis.

PMID- 15741330
TI  - L-Arginine increases the solubility of unfolded species of hen egg white
      lysozyme.
AB  - L-Arginine (L-Arg) has been widely used as an enhancer of protein renaturation.
      The mechanism behind its action is still not fully understood. Using hen egg
      white lysozyme as a model protein, we present data that clearly demonstrate the
      suppression of the aggregation of denatured protein by L-Arg. By chemical
      modification of free cysteines, a series of unfolded lysozyme species were
      obtained that served as models for unfolded and intermediate states during the
      process of oxidative refolding. An increased equilibrium solubility of unfolded
      species and intermediates in the presence of L-Arg seems to be its major
      mechanism of action.

PMID- 15741331
TI  - Rotational orientation of monomers within a designed homo-oligomer transmembrane
      helical bundle.
AB  - A peptide designed to form a homo-oligomeric transmembrane helical bundle was
      reconstituted into lipid bilayers and studied by using (2)H NMR (nuclear magnetic
      resonance) with magic angle spinning to confirm that the helical interface
      corresponds to the interface intended in the design. The peptide belongs to a
      family of model peptides derived from a membrane-solubilized version of the water
      soluble coiled-coil GCN4-P1. The variant studied here contains two asparagines
      thought to engage in interhelical hydrogen bonding critical to the formation of a
      stable trimer. For the NMR studies, three different peptides were synthesized,
      each with one of three consecutive leucines in the transmembrane region deuterium
      labeled. Prior to NMR data collection, polarized infrared spectroscopy was used
      to establish that the peptides were reconstituted in lipid bilayers in a
      transmembrane helical conformation. The (2)H NMR line shapes of the three
      different peptides are consistent with a trimer structure formed by the designed
      peptide that is stabilized by inter-helical hydrogen bonding of asparagines at
      positions 7 and 14.

PMID- 15741332
TI  - Cryoelectron microscopy reveals new features in the three-dimensional structure
      of phosphorylase kinase.
AB  - Phosphorylase kinase (PhK), a regulatory enzyme in the cascade activation of
      glycogenolysis, is a 1.3-MDa hexadecameric complex, (alphabetagammadelta)(4). PhK
      comprises two arched octameric (alphabetagammadelta)(2) lobes that are oriented
      back-to-back with overall D(2) symmetry and connected by small bridges. These
      interlobal bridges, arguably the most questionable structural component of PhK,
      are one of several structural features that potentially are artifactually
      generated or altered by conventional sample preparation techniques for electron
      microscopy (EM). To minimize such artifacts, we have solved by cryoEM the first
      three-dimensional (3D) structure of nonactivated PhK from images of frozen
      hydrated molecules of the kinase. Minimal dose electron micrographs of PhK in
      vitreous ice revealed particles in a multitude of orientations. A simple model
      was used to orient the individual images for 3D reconstruction, followed by
      multiple rounds of refinement. Three-dimensional reconstruction of nonactivated
      PhK from approximately 5000 particles revealed a bridged, bilobal molecule with a
      resolution estimated by Fourier shell correlation analysis at 25 A. This new
      structure suggests that several prominent features observed in the structure of
      PhK derived from negatively stained particles arise as artifacts of specimen
      preparation. In comparison to the structure from negative staining, the cryoEM
      structure shows three important differences: (1) a dihedral angle between the two
      lobes of approximately 90 degrees instead of 68 degrees, (2) a compact rather
      than extended structure for the lobes, and (3) the presence of four, rather than
      two, connecting bridges, which provides the first direct evidence for these
      components as authentic elements of the kinase solution structure.

PMID- 15741333
TI  - Ca2+-induced structural changes in phosphorylase kinase detected by small-angle X
      ray scattering.
AB  - Phosphorylase kinase (PhK), a 1.3-MDa (alphabetagammadelta)(4) hexadecameric
      complex, is a Ca(2+)-dependent regulatory enzyme in the cascade activation of
      glycogenolysis. PhK comprises two arched (alphabetagammadelta)(2) octameric lobes
      that are oriented back-to-back with overall D(2) symmetry and joined by
      connecting bridges. From chemical cross-linking and electron microscopy, it is
      known that the binding of Ca(2+) by PhK perturbs the structure of all its
      subunits and promotes redistribution of density throughout both its lobes and
      bridges; however, little is known concerning the interrelationship of these
      effects. To measure structural changes induced by Ca(2+) in the PhK complex in
      solution, small-angle X-ray scattering was performed on nonactivated and Ca(2+)
      activated PhK. Although the overall dimensions of the complex were not affected
      by Ca(2+), the cation did promote a shift in the distribution of the scattering
      density within the hydrated volume occupied by the PhK molecule, indicating a
      Ca(2+)-induced conformational change. Computer-generated models, based on
      elements of the known structure of PhK from electron microscopy, were constructed
      to aid in the interpretation of the scattering data. Models containing two
      ellipsoids and four cylinders to represent, respectively, the lobes and bridges
      of the PhK complex provided theoretical scattering profiles that accurately fit
      the experimental data. Structural differences between the models representing the
      nonactivated and Ca(2+)-activated conformers of PhK are consistent with Ca(2+)
      induced conformational changes in both the lobes and the interlobal bridges.

PMID- 15741334
TI  - Self-cleavage of fusion protein in vivo using TEV protease to yield native
      protein.
AB  - Overproduction of proteins from cloned genes using fusion protein expression
      vectors in Escherichia coli and eukaryotic cells has increased the quantity of
      protein produced. This approach has been widely used in producing soluble
      recombinant proteins for structural and functional analysis. One major
      disadvantage, however, of applying this approach for clinical or bioindustrial
      uses is that proteolytic removal of the fusion carrier is tedious, expensive, and
      often results in products with additional amino acid residues than the native
      proteins. Here we describe a new method for productions of native proteins with
      original amino termini in vivo via intracellular self-cleavage of the fusion
      protein using tobacco etch virus (TEV) protease. Our design allows one to
      simultaneously clone any gene into multiple fusion protein vectors using two
      unique cloning sites (i.e., SnaBI and XhoI) without restriction digestion, and
      then rapidly identifies those constructs producing soluble native proteins. This
      method will make the fusion protein approach more feasible for protein drug
      research.

PMID- 15741335
TI  - Deamidation and disulfide bridge formation in human calbindin D28k with effects
      on calcium binding.
AB  - Calbindin D(28k) (calbindin) is a cytoplasmic protein expressed in the central
      nervous system, which is implied in Ca(2+) homeostasis and enzyme regulation. A
      combination of biochemical methods and mass spectrometry has been used to
      identify post-translational modifications of human calbindin. The protein was
      studied at 37 degrees C or 50 degrees C in the presence or absence of Ca(2+). One
      deamidation site was identified at position 203 (Asn) under all conditions.
      Kinetic experiments show that deamidation of Asn 203 occurs at a rate of 0.023 h(
      1) at 50 degrees C for Ca(2+)-free calbindin. Deamidation is slower for the
      Ca(2+)-saturated protein. The deamidation process leads to two Asp iso-forms,
      regular Asp and iso-Asp. The form with regular Asp 203 binds four Ca(2+) ions
      with high affinity and positive cooperativity, i.e., in a very similar manner to
      non-deamidated protein. The form with beta-aspartic acid (or iso-Asp 203) has
      reduced affinity for two or three sites leading to sequential Ca(2+) binding,
      i.e., the Ca(2+)-binding properties are significantly perturbed. The status of
      the cysteine residues was also assessed. Under nonreducing conditions, cysteines
      94 and 100 were found both in reduced and oxidized form, in the latter case in an
      intramolecular disulfide bond. In contrast, cysteines 187, 219, and 257 were not
      involved in any disulfide bonds. Both the reduced and oxidized forms of the
      protein bind four Ca(2+) ions with high affinity in a parallel manner and with
      positive cooperativity.

PMID- 15741336
TI  - Modulation of cooperativity in Mycobacterium tuberculosis NADPH-ferredoxin
      reductase: cation-and pH-induced alterations in native conformation and
      destabilization of the NADP+-binding domain.
AB  - FprA, a Mycobacterium tuberculosis NADPH-ferredoxin reductase, consists of two
      structural domains, a FAD-binding and a NADP-binding domain, respectively. For
      the first time, we demonstrated that native FprA, on thermal treatment underwent
      partial denaturation with unfolding of only the FAD-binding domain and release of
      the protein-bound flavin. The NADP-binding domain of this protein is highly
      resistant to denaturation under these conditions. However, the presence of either
      150 mM NaCl or KCl or 10 muM MgCl(2) or CaCl(2) or slightly acidic pH of 6.0
      resulted in a highly cooperative and complete thermal unfolding of the protein.
      Physicochemical investigations showed that the monovalent cations or low
      concentrations of divalent cations induced compaction of the protein
      conformation. However, divalent cations at higher concentrations resulted in FAD
      release leading to stabilization of an enzymatically inactive apoenzyme. Detailed
      thermal denaturation studies on the native protein and the isolated NADP-binding
      domain showed that cations and pH 6.0 destabilized only the heat-stable NADP
      binding domain. The experimental studies demonstrate that modulation of
      intramolecular ionic interactions induce significant conformational changes in
      the NADP-binding domain of FprA, resulting in a substantial increase in the
      structural cooperativity of the whole molecule. The results presented in this
      paper are of importance as they demonstrate alterations in the native three
      dimensional structure of FprA and cooperativity in protein molecule on slight
      alteration of pH or modification of ionic interactions in protein.

PMID- 15741337
TI  - Crystal structure of a novel polyisoprenoid-binding protein from Thermus
      thermophilus HB8.
AB  - The isoprenoid quinones exist widely among prokaryotes and eukaryotes. They play
      essential roles in respiratory electron transport and in controlling oxidative
      stress and gene regulation. In the isoprenoid quinone biosynthetic pathway,
      polyprenyl pyrophosphates are used as isoprenoid side-chain precursors. Here we
      report the crystal structure of a novel polyprenyl pyrophosphate binding protein,
      TT1927b, from Thermus thermophilus HB8, complexed with its ligand. This protein
      belongs to the YceI-like family in the Pfam database, and its sequence homologs
      are present in a broad range of bacteria and archaea. The structure consists of
      an extended, eight-stranded, antiparallel beta-barrel. In the hydrophobic pore of
      the barrel, the protein binds the polyisoprenoid chain by hydrophobic
      interactions. Its overall structure resembles the lipocalin fold, but there is no
      sequence homology between TT1927b and the lipocalin family of proteins.

PMID- 15741338
TI  - The conformation of the pore region of the M2 proton channel depends on lipid
      bilayer environment.
AB  - The M2 protein from influenza A virus is a 97-amino-acid protein with a single
      transmembrane helix that forms proton-selective channels essential to virus
      function. The hydrophobic transmembrane domain of the M2 protein (M2TM) contains
      a sequence motif that mediates the formation of functional tetramers in membrane
      environments. A variety of structural models have previously been proposed which
      differ in the degree of helix tilt, with proposed tilts ranging from
      approximately 15 degrees to 38 degrees . An important issue for understanding the
      structure of M2TM is the role of peptide-lipid interactions in the stabilization
      of the lipid bilayer bound tetramer. Here, we labeled the N terminus of M2TM with
      a nitroxide and studied the tetramer reconstituted into lipid bilayers of
      different thicknesses using EPR spectroscopy. Analyses of spectral changes
      provide evidence that the lipid bilayer does influence the conformation. The
      structural plasticity displayed by M2TM in response to membrane composition may
      be indicative of functional requirements for conformational change. The various
      structural models for M2TM proposed to date--each defined by a different set of
      criteria and in a different environment--might provide snapshots of the distinct
      conformational states sampled by the protein.

PMID- 15741339
TI  - Misfolded forms of glyceraldehyde-3-phosphate dehydrogenase interact with GroEL
      and inhibit chaperonin-assisted folding of the wild-type enzyme.
AB  - We studied the interaction of chaperonin GroEL with different misfolded forms of
      tetrameric phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPDH): (1)
      GAPDH from rabbit muscles with all SH-groups modified by 5,5'-dithiobis(2
      nitrobenzoate); (2) O-R-type dimers of mutant GAPDH from Bacillus
      stearothermophilus with amino acid substitutions Y283V, D282G, and Y283V/W84F,
      and (3) O-P-type dimers of mutant GAPDH from B. stearothermophilus with amino
      acid substitutions Y46G/S48G and Y46G/R52G. It was shown that chemically modified
      GAPDH and the O-R-type mutant dimers bound to GroEL with 1:1 stoichiometry and
      dissociation constants K(d) of 0.4 and 0.9 muM, respectively. A striking feature
      of the resulting complexes with GroEL was their stability in the presence of Mg
      ATP. Chemically modified GAPDH and the O-R-type mutant dimers inhibited GroEL
      assisted refolding of urea-denatured wild-type GAPDH from B. stearothermophilus
      but did not affect its spontaneous reactivation. In contrast to the O-R-dimers,
      the O-P-type mutant dimers neither bound nor affected GroEL-assisted refolding of
      the wild-type GAPDH. Thus, we suggest that interaction of GroEL with certain
      types of misfolded proteins can result in the formation of stable complexes and
      the impairment of chaperonin activity.

PMID- 15741340
TI  - Kinetic and crystallographic studies on 2-(beta-D-glucopyranosyl)-5-methyl-1, 3,
      4-oxadiazole, -benzothiazole, and -benzimidazole, inhibitors of muscle glycogen
      phosphorylase b. Evidence for a new binding site.
AB  - In an attempt to identify leads that would enable the design of inhibitors with
      enhanced affinity for glycogen phosphorylase (GP), that might control
      hyperglycaemia in type 2 diabetes, three new analogs of beta-D-glucopyranose, 2
      (beta-D-glucopyranosyl)-5-methyl-1, 3, 4-oxadiazole, -benzothiazole, and 
      benzimidazole were assessed for their potency to inhibit GPb activity. The
      compounds showed competitive inhibition (with respect to substrate Glc-1-P) with
      K(i) values of 145.2 (+/-11.6), 76 (+/-4.8), and 8.6 (+/-0.7) muM, respectively.
      In order to establish the mechanism of this inhibition, crystallographic studies
      were carried out and the structures of GPb in complex with the three analogs were
      determined at high resolution (GPb-methyl-oxadiazole complex, 1.92 A; GPb
      benzothiazole, 2.10 A; GPb-benzimidazole, 1.93 A). The complex structures
      revealed that the inhibitors can be accommodated in the catalytic site of T-state
      GPb with very little change of the tertiary structure, and provide a
      rationalization for understanding variations in potency of the inhibitors. In
      addition, benzimidazole bound at the new allosteric inhibitor or indole binding
      site, located at the subunit interface, in the region of the central cavity, and
      also at a novel binding site, located at the protein surface, far removed
      (approximately 32 A) from the other binding sites, that is mostly dominated by
      the nonpolar groups of Phe202, Tyr203, Val221, and Phe252.

PMID- 15741341
TI  - The monomer-dimer equilibrium of stromal cell-derived factor-1 (CXCL 12) is
      altered by pH, phosphate, sulfate, and heparin.
AB  - Chemokines, like stromal cell-derived factor-1 (SDF1/CXCL12), are small secreted
      proteins that signal cells to migrate. Because SDF1 and its receptor CXCR4 play
      important roles in embryonic development, cancer metastasis, and HIV/AIDS, this
      chemokine signaling system is the subject of intense study. However, it is not
      known whether the monomeric or dimeric structure of SDF1 is responsible for
      signaling in vivo. Previous structural studies portrayed the SDF1 structure as
      either strictly monomeric in solution or dimeric when crystallized. Here, we
      report two-dimensional NMR, pulsed-field gradient diffusion and fluorescence
      polarization measurements at various SDF1 concentrations, solution conditions,
      and pH. These results demonstrate that SDF1 can form a dimeric structure in
      solution, but only at nonacidic pH when stabilizing counterions are present.
      Thus, while the previous NMR structural studies were performed under acidic
      conditions that strongly promote the monomeric state, crystallographic studies
      used nonacidic buffer conditions that included divalent anions shown here to
      promote dimerization. This pH-sensitive aggregation behavior is explained by a
      dense cluster of positively charged residues at the SDF1 dimer interface that
      includes a histidine side chain at its center. A heparin disaccharide shifts the
      SDF1 monomer-dimer equilibrium in the same manner as other stabilizing anions,
      suggesting that glycosaminoglycan binding may be coupled to SDF1 dimerization in
      vivo.

PMID- 15741342
TI  - Structural basis of the temperature transition of Pf1 bacteriophage.
AB  - The filamentous bacteriophage Pf1 undergoes a reversible temperature-dependent
      transition that is also influenced by salt concentrations. This structural
      responsiveness may be a manifestation of the important biological property of
      flexibility, which is necessary for long, thin filamentous assemblies as a
      protection against shear forces. To investigate structural changes in the major
      coat protein, one- and two-dimensional solid-state NMR spectra of concentrated
      solutions of Pf1 bacteriophage were acquired, and the structure of the coat
      protein determined at 0 degrees C was compared with the structure previously
      determined at 30 degrees C. Despite dramatic differences in the NMR spectra, the
      overall change in the coat protein structure is small. Changes in the orientation
      of the C-terminal helical segment and the conformation of the first five residues
      at the N-terminus are apparent. These results are consistent with prior studies
      by X-ray fiber diffraction and other biophysical methods.

PMID- 15741343
TI  - Distinguishing multiple chemotaxis Y protein conformations with laser-polarized
      129Xe NMR.
AB  - The chemical shift of the (129)Xe NMR signal has been shown to be extremely
      sensitive to the local environment around the atom and has been used to follow
      processes such as ligand binding by bacterial periplasmic binding proteins. Here
      we show that the (129)Xe shift can sense more subtle changes: magnesium binding,
      BeF(3)(-) activation, and peptide binding by the Escherichia coli chemotaxis Y
      protein. (1)H-(15)N correlation spectroscopy and X-ray crystallography were used
      to identify two xenon-binding cavities in CheY that are primarily responsible for
      the shift changes. One site is near the active site, and the other is near the
      peptide binding site.

PMID- 15741344
TI  - NMR characterization of the Escherichia coli nitrogen regulatory protein IIANtr
      in solution and interaction with its partner protein, NPr.
AB  - The solution form of IIA(Ntr) from Escherichia coli and its interaction with its
      partner protein, NPr, were characterized by nuclear magnetic resonance (NMR)
      spectroscopy. The diffusion coefficient of the protein (1.13 x 10(-6) cm/sec)
      falls between that of HPr (approximately 9 kDa) and the N-terminal domain of E.
      coli enzyme I (approximately 30 kDa), indicating that the functional form of
      IIA(Ntr) is a monomer (approximately 18 kDa) in solution. Thus, the dimeric
      structure of the protein found in the crystal is an artifact of crystal packing.
      The residual dipolar coupling data of IIA(Ntr) (covering residues 11-155)
      measured in the absence and presence of a 4% polyethyleneglycol-hexanol liquid
      crystal alignment medium fit well to the coordinates of both molecule A and
      molecule B of the dimeric crystal structure, indicating that the 3D structures in
      solution and in the crystal are indeed similar for that protein region. However,
      only molecule A possesses an N-terminal helix identical to that derived from
      chemical shifts of IIA(Ntr) in solution. Further, the (15)N heteronuclear nuclear
      Overhauser effect (NOE) data also support molecule A as the representative
      structure in solution, with the terminal residues 1-8 and 158-163 more mobile.
      Chemical shift mapping identified the surface on IIA(Ntr) for NPr binding.
      Residues Gly61, Asp115, Ser125, Thr156, and nearby regions of IIA(Ntr) are more
      perturbed and participate in interaction with NPr. The active-site His73 of
      IIA(Ntr) for phosphoryl transfer was found in the Ndelta1-H tautomeric state.
      This work lays the foundation for future structure and function studies of the
      signal transducing proteins from this nitrogen pathway.

PMID- 15741345
TI  - Bcl-XL as a fusion protein for the high-level expression of membrane-associated
      proteins.
AB  - An Escherichia coli plasmid vector for the high-level expression of hydrophobic
      membrane proteins is described. The plasmid, pBCL, directs the expression of a
      target polypeptide fused to the C terminus of a mutant form of the anti-apoptotic
      Bcl-2 family protein, Bcl-XL, where the hydrophobic C terminus has been deleted,
      and Met residues have been mutated to Leu to facilitate CNBr cleavage after a
      single Met inserted at the beginning of the target sequence. Fusion protein
      expression is in inclusion bodies, simplifying the protein purification steps.
      Here we report the high-level production of PLM, a membrane protein that is a
      member of the FXYD family of tissue-specific and physiological-state-specific
      auxiliary subunits of the Na,K-ATPase, expressed abundantly in heart and skeletal
      muscle. We demonstrate that milligram quantities of pure, isotopically labeled
      protein can be obtained easily and in little time with this system.

PMID- 15741346
TI  - Solution structure of At3g04780.1-des15, an Arabidopsis thaliana ortholog of the
      C-terminal domain of human thioredoxin-like protein.
AB  - The structure of At3g04780.1-des15, an Arabidopsis thaliana ortholog of the C
      terminal domain of human thioredoxin-like protein, was determined by NMR
      spectroscopy. The structure is dominated by a beta-barrel sandwich. A two
      stranded anti-parallel beta-sheet, which seals off one end of the beta-barrel, is
      flanked by two flexible loops rich in acidic amino acids. Although this fold
      often provides a ligand binding site, the structure did not reveal an appreciable
      cavity inside the beta-barrel. The three-dimensional structure of At3g04780.1
      des15 provides an entry point for understanding its functional role and those of
      its mammalian homologs.

PMID- 15741347
TI  - Helix periodicity, topology, and dynamics of membrane-associated alpha-synuclein.
AB  - The protein alpha-Synuclein (aS) is a synaptic vesicle-associated regulator of
      synaptic strength and dopamine homeostasis with a pathological role in
      Parkinson's disease. The normal function of aS depends on a membrane-associated
      conformation that is adopted upon binding to negatively charged lipid surfaces.
      Previously we found that the membrane-binding domain of aS is helical and
      suggested that it may exhibit an unusual structural periodicity. Here we present
      a study of the periodicity, topology, and dynamics of detergent micelle-bound aS
      using paramagnetic spin labels embedded in the micelle or attached to the
      protein. We show that the helical region of aS completes three full turns every
      11 residues, demonstrating the proposed 11/3 periodicity. We also find that the
      membrane-binding domain is partially buried in the micelle surface and bends
      toward the hydrophobic interior, but does not traverse the micelle. Deeper
      submersion of certain regions within the micelle, including the unique lysine
      free sixth 11-residue repeat, is observed and may be functionally important.
      There are no long-range tertiary contacts within this domain, indicating a highly
      extended configuration. The backbone dynamics of the micelle-bound region are
      relatively uniform with a slight decrease in flexibility observed toward the C
      terminal end. These results clarify the topological features of aS bound to
      membrane-mimicking detergent micelles, with implications for aS function and
      pathology.

PMID- 15741348
TI  - Dioxane contributes to the altered conformation and oligomerization state of a
      designed engrailed homeodomain variant.
AB  - Our goal was to compute a stable, full-sequence design of the Drosophila
      melanogaster engrailed homeodomain. Thermal and chemical denaturation data
      indicated the design was significantly more stable than was the wild-type
      protein. The data were also nearly identical to those for a similar, later full
      sequence design, which was shown by NMR to adopt the homeodomain fold: a three
      helix, globular monomer. However, a 1.65 A crystal structure of the design
      described here turned out to be of a completely different fold: a four-helix,
      rodlike tetramer. The crystallization conditions included approximately 25%
      dioxane, and subsequent experiments by circular dichroism and sedimentation
      velocity analytical ultracentrifugation indicated that dioxane increases the
      helicity and oligomerization state of the designed protein. We attribute at least
      part of the discrepancy between the target fold and the crystal structure to the
      presence of a high concentration of dioxane.

PMID- 15741349
TI  - Primary erythromelalgia in a child responding to intravenous lidocaine and oral
      mexiletine treatment.
AB  - Erythromelalgia is a rare, chronic, debilitating condition characterized by
      redness, warmth, and severe burning pain of the distal extremities. The feet are
      more commonly affected than the hands. Pain is precipitated by increases in
      temperature and by exercise. Patients often obtain relief by immersing the
      affected extremity in cold water. The pain is often refractory to treatment. For
      many patients, multiple pain medications have been useless in achieving complete
      relief of pain symptoms. Previous reports of erythromelalgia among adolescents
      indicated prolonged relief of pain with sodium nitroprusside infusions, epidural
      infusions of local anesthetics, or gabapentin treatment. We present a case of an
      11-year-old, white, male child with primary erythromelalgia, whose initial
      symptoms started in his preschool years and whose childhood was marked by
      escalating episodes of pain with warmth and redness of his feet, precipitated
      especially by increases in temperature and by activity. All conventional pain
      management techniques had failed to relieve our patient of his symptoms, and he
      obtained some relief only by soaking his affected extremities in ice water. He
      had experienced minimal benefit from seeing a pain psychologist, who helped him
      develop techniques to cope with the pain. At the time of presentation, the
      patient's episodes of pain had increased to 15 to 20 per day, and there was
      evidence of chronic immersion injury to the skin of his feet. Before his most
      recent hospitalization, the pain had spread to involve his hands as well. The
      patient was overwhelmed with anxiety and could not participate in school or
      social activities at the time of admission. During his current hospitalization,
      he did show some therapeutic response to sodium nitroprusside infusion, which
      unfortunately had to be discontinued because of side effects and because his
      family desired to leave the ICU environment, which was stressful to the patient.
      He also had some response to lumbar epidural infusion of local anesthetics, which
      could not be continued because he found the motor blockade that accompanied his
      analgesia intolerable. However, intravenous lidocaine infusion, with subsequent
      transition to oral mexiletine therapy, proved very effective in reducing the
      frequency and severity of the pain episodes. The patient was discharged from the
      hospital with oral mexiletine therapy and has been monitored at the pain
      management clinic. He returned to and completed school, attended summer camp, and
      enjoys an active happy life. He walks without precipitating pain in his feet and
      sleeps 9 to 10 hours every night. He has needed to soak his feet on only 4
      occasions in the 6 months since his discharge from the hospital. His quality of
      life has improved significantly. He has shown no evidence of liver toxicity, and
      his mexiletine levels have been stable.

PMID- 15741350
TI  - Hypospadias in Washington State: maternal risk factors and prevalence trends.
AB  - OBJECTIVE: Maternal risk factors for hypospadias are poorly defined, and there is
      debate about temporal trends in hypospadias prevalence. We examined select
      maternal characteristics as possible risk factors for hypospadias among male
      offspring and evaluated yearly prevalence rates in Washington State. METHODS: We
      performed a population-based, case-control study using linked birth-hospital
      discharge data from Washington State for 1987-1997 and prevalence data for 1987
      2002. All cases of hypospadias were identified on the basis of International
      Classification of Diseases, Ninth Revision, codes from the birth hospitalization
      (N = 2155). Five control subjects were randomly selected for each case subject
      from the remaining singleton births, frequency matched according to year of birth
      (N = 10775). Maternal and infant characteristics were ascertained from the birth
      certificate. Logistic regression was used to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs). Yearly prevalence was determined by dividing the
      total number of hypospadias cases by the number of male singleton live births for
      each year. RESULTS: The risk of delivering an affected male infant increased with
      advancing maternal age; relative to women <20 years of age, those >40 years of
      age were at greatest risk (OR: 1.70; 95% CI: 1.17-2.48). Infants of nonwhite
      women were generally at decreased risk. Infants born to women with preexisting
      diabetes mellitus were at greater risk than those born to women without diabetes
      (OR: 2.18; 95% CI: 1.03-4.60); however, this was not observed for infants born to
      women with gestational diabetes. The birth prevalence of hypospadias in 2002 was
      5.0 cases per 1000 male births, not significantly different from that in 1987.
      CONCLUSION: Older maternal age, white race, and preexisting diabetes were
      associated with increased risk of hypospadias among male offspring. The
      prevalence of hypospadias in Washington State did not increase significantly
      between 1987 and 2002.

PMID- 15741351
TI  - Homeostasis model assessment is more reliable than the fasting glucose/insulin
      ratio and quantitative insulin sensitivity check index for assessing insulin
      resistance among obese children and adolescents.
AB  - OBJECTIVE: Simple fasting methods to measure insulin resistance, such as the
      homeostasis model assessment (HOMA), fasting glucose/insulin ratio (FGIR), and
      quantitative insulin sensitivity check index (QUICKI) methods, have been widely
      promoted for adult studies but have not been evaluated formally among children
      and adolescents. The aim of this study was to compare the HOMA, FGIR, and QUICKI
      methods for measuring insulin resistance, expressed by oral glucose tolerance
      test (OGTT) results, among obese children and adolescents. METHODS: Fifty-seven
      pubertal obese children and adolescents (30 girls and 27 boys; mean age, 12.04 +/
      2.90 years; mean BMI: 29.57 +/- 5.53) participated in the study. All
      participants underwent an OGTT. Blood samples were obtained 0, 30, 60, 90, and
      120 minutes after oral glucose administration for glucose and insulin
      measurements, and 2 separate groups were studied, according to the presence or
      absence of insulin resistance. HOMA, FGIR, and QUICKI methods were studied for
      validation of insulin resistance determined with the OGTT for these groups.
      RESULTS: The groups consisted of 25 obese children and adolescents with insulin
      resistance (14 girls and 11 boys; mean age: 12.88 +/- 2.88 years; mean BMI: 31.29
      +/- 5.86) and 32 subjects without insulin resistance (16 girls and 16 boys; mean
      age: 11.38 +/- 2.79 years; mean BMI: 28.23 +/- 4.94). There were significant
      differences in the mean HOMA (6.06 +/- 4.98 and 3.42 +/- 3.14, respectively) and
      QUICKI (0.313 +/- 0.004 and 0.339 +/- 0.004, respectively) values between the 2
      groups. Sensitivity and specificity calculations based on insulin resistance with
      receiver operating characteristic curve analysis indicated that HOMA had high
      sensitivity and specificity for measuring insulin resistance. CONCLUSIONS: As a
      measure of insulin resistance among children and adolescents, HOMA is more
      reliable than FGIR and QUICKI. The present HOMA cutoff point for diagnosis of
      insulin resistance is 3.16. The HOMA cutoff point of >2.5 is valid for adults but
      not for adolescents.

PMID- 15741352
TI  - National autism prevalence trends from United States special education data.
AB  - OBJECTIVE: Reports of large increases in autism prevalence have been a matter of
      great concern to clinicians, educators, and parents. This analysis uses a
      national data source to compare the prevalence of autism with that of other
      disabilities among successive birth cohorts of US school-aged children. DESIGN:
      Comparison of birth cohort curves constructed from administrative data. SETTING
      AND POPULATION: US children 6 to 17 years of age between 1992 and 2001. MAIN
      OUTCOME MEASURES: A disability category classification of autism, mental
      retardation, speech and language impairment, traumatic brain injury, or other
      health impairment, as documented by state departments of education and reported
      to the Office of Special Education Programs, US Department of Education. RESULTS:
      Prevalences of disability category classifications for annual birth cohorts from
      1975 to 1995 were calculated by using denominators from US Census Bureau
      estimates. For the autism classification, there were birth cohort differences,
      with prevalences increasing among successive (younger) cohorts. The increases
      were greatest for annual cohorts born from 1987 to 1992. For cohorts born after
      1992, the prevalence increased with each successive year but the increases did
      not appear to be as great, although there were fewer data points available within
      cohorts. No concomitant decreases in categories of mental retardation or
      speech/language impairment were seen. Curves for other health impairments, the
      category including children with attention-deficit/hyperactivity disorder, also
      showed strong cohort differences. CONCLUSIONS: Cohort curves suggest that autism
      prevalence has been increasing with time, as evidenced by higher prevalences
      among younger birth cohorts. The narrowing in vertical separation of the cohort
      curves in recent years may mark a slowing in the autism prevalence increase.

PMID- 15741353
TI  - International collaborative study of intracytoplasmic sperm injection-conceived,
      in vitro fertilization-conceived, and naturally conceived 5-year-old child
      outcomes: cognitive and motor assessments.
AB  - OBJECTIVE: To date, very few studies have been conducted on the
      neurodevelopmental well-being of children conceived through intracytoplasmic
      sperm injection (ICSI). The limitations of these studies often include a lack of
      comparison with a demographically matched, naturally conceived (NC) group and the
      investigation of only very young children, with relatively small samples sizes.
      One study showed that there were no differences in IQ scores among ICSI
      conceived, in vitro fertilization (IVF)-conceived, and NC children at 5 years of
      age. Unfortunately, psychomotor development was not assessed in that study.
      Because findings regarding these children's cognitive and motor development are
      inconclusive, the aim of this study was to shed more light on the cognitive and
      motor development of 5-year-old ICSI-conceived children. METHODS: A total of 511
      ICSI-conceived children were compared with 424 IVF-conceived children and 488 NC
      controls. Children were recruited in 5 European countries, ie, Belgium, Denmark,
      Greece, Sweden, and the United Kingdom. Participation rates ranged from 45% to
      96% in the ICSI and IVF groups and from 34% to 78% in the NC group. Cognitive and
      motor development was assessed with the Wechsler Preschool and Primary Scale of
      Intelligence-Revised (WPPSI-R) and McCarthy Scales of Children's Abilities (MSCA)
      Motor Scale, respectively. The WPPSI-R consists of 2 major scales, ie, Verbal and
      Performance, each including 6 subtests. The 6 Performance Scale subtests are
      object assembly, geometric design, block design, mazes, picture completion, and
      animal pegs. The 6 Verbal Scale subtests are information, comprehension,
      arithmetic, vocabulary, similarities, and sentences. Scores on the Performance
      and Verbal Scale subtests are summed to yield the performance IQ (PIQ) and verbal
      IQ (VIQ), respectively. Scores on both the Performance Scale and the Verbal Scale
      yield the full-scale IQ (FSIQ). IQ scales have a mean score of 100 and a SD of
      15. Each subtest has a mean score of 10 and a SD of 3. The MSCA consists of 6
      scales, ie, Verbal, Perceptual-Performance, Quantitative, General Cognitive,
      Memory, and Motor Scale. In this study, only the Motor Scale was administered.
      This scale assesses the child's coordination during performance of a variety of
      gross- and fine-motor tasks. Leg coordination, arm coordination, and imitative
      action tests provide measures of gross-motor ability. Draw-a-design and draw-a
      child assess fine-motor coordination, as revealed by the levels of hand
      coordination and finger dexterity. The mean score for this test is 50, with a SD
      of . RESULTS: No differences were identified among ICSI, IVF, and NC children
      with respect to VIQ, PIQ, or FSIQ scores of the WPPSI-R. Furthermore, there were
      no differences between groups regarding the discrepancy between VIQ and PIQ
      scores. These results were not influenced by gender, country, or maternal
      educational level. However, in the subgroup of firstborn children with mothers
      who gave birth at an older age (33-45 years), NC children obtained significantly
      better VIQ and FSIQ scores than did children conceived through assisted
      reproductive technologies. These differences in VIQ and FSIQ scores between
      ICSI/IVF and NC children were relative, because NC children scored <1 IQ point
      higher than ICSI/IVF children. Therefore, these scores show no clinical
      relevance. For Verbal Scale subtests, variables such as age of the mother at the
      time of the birth, educational level of the mother, and gender and nationality of
      the child interacted with mode of conception, resulting in clinically irrelevant
      differences between scores for the ICSI/IVF and NC groups on the arithmetic,
      vocabulary, and comprehension subtests. For Performance Scale subtests, these
      same demographic factors interacted with mode of conception for the block design,
      object assembly, and animal pegs subtests, again resulting in clinically
      irrelevant differences among groups. In the 3 groups (ICSI, IVF, and NC), we
      observed equal numbers of children scoring below 1 SD from the mean on the WPPSI
      R and the MSCA. CONCLUSIONS: This study includes a substantial number of children
      from several European countries. Apart from a few interaction effects between
      mode of conception and demographic variables, no differences were found when
      ICSI, IVF, and NC scores on the WPPSI-R and MSCA Motor Scale were compared.
      Nevertheless, the aforementioned interaction effects could indicate that
      demographic variables such as maternal age at the time of the birth and maternal
      educational level play different roles in the cognitive development of IVF and
      ICSI children, compared with NC children. Additional research is needed to
      explore and verify this finding. Previous studies revealed that ICSI children, in
      comparison with NC children, more frequently obtained scores below 1 SD from the
      mean on 3 subtests of the Performance Scale (object assembly, block design, and
      mazes) or showed a trend of 5.2% of ICSI children, compared with 2.5% of IVF
      children and 0.9% of NC children, obtaining a score below 1 SD from the mean, but
      those findings were not confirmed in this study. Here no differences were found
      among the 3 groups in the numbers of children scoring below 1 SD from the mean on
      the VIQ, PIQ, and FSIQ tests and the Verbal and Performance Scale subtests. Motor
      development results were somewhat more conclusive. There were no differences
      between the scores of ICSI, IVF, and NC children on the MCSA Motor Scale. No
      interaction effects were found between mode of conception and demographic
      variables, indicating that these results are not influenced by gender,
      nationality, maternal educational level, or maternal age at the time of the
      birth. Furthermore, equal proportions of children in all 3 groups scored below 1
      SD from the mean. The results of this study are reassuring for parents who
      conceived through ICSI (or IVF). The findings indicate that the motor and
      cognitive development of their offspring is very similar to that of NC children.
      However, demographic factors such as maternal educational level and maternal age
      at the time of the birth might play different roles in the cognitive development
      of ICSI and IVF children, compared with NC children.

PMID- 15741354
TI  - Metabolic syndrome in childhood: association with birth weight, maternal obesity,
      and gestational diabetes mellitus.
AB  - OBJECTIVE: Childhood obesity has contributed to an increased incidence of type 2
      diabetes mellitus and metabolic syndrome (MS) among children. Intrauterine
      exposure to diabetes and size at birth are risk factors for type 2 diabetes
      mellitus, but their association with MS in childhood has not been demonstrated.
      We examined the development of MS among large-for-gestational-age (LGA) and
      appropriate-for-gestational age (AGA) children. STUDY DESIGN: The major
      components of MS (obesity, hypertension, dyslipidemia, and glucose intolerance)
      were evaluated in a longitudinal cohort study of children at age 6, 7, 9, and 11
      years who were LGA (n = 84) or AGA (n = 95) offspring of mothers with or without
      gestational diabetes mellitus (GDM). The cohort consisted of 4 groups, ie, LGA
      offspring of control mothers, LGA offspring of mothers with GDM, AGA offspring of
      control mothers, and AGA offspring of mothers with GDM. Biometric and
      anthropometric measurements were obtained at 6, 7, 9, and 11 years. Biochemical
      testing included measurements of postprandial glucose and insulin levels and high
      density lipoprotein (HDL) cholesterol levels at 6 and 7 years and of fasting
      glucose, insulin, triglyceride, and HDL cholesterol levels at 9 and 11 years. We
      defined the components of MS as (1) obesity (BMI >85th percentile for age), (2)
      diastolic or systolic blood pressure >95th percentile for age, (3) postprandial
      glucose level >140 mg/dL or fasting glucose level >110 mg/dL, (4) triglyceride
      level >95th percentile for age, and (5) HDL level <5th percentile for age.
      RESULTS: There were no differences in baseline characteristics (gender, race,
      socioeconomic status, and maternal weight gain during pregnancy) for the 4 groups
      except for birth weight, but there was a trend toward a higher prevalence of
      maternal obesity before pregnancy in the LGA/GDM group. Obesity (BMI >85th
      percentile) at 11 years was present in 25% to 35% of the children, but rates were
      not different between LGA and AGA offspring. There was a trend toward a higher
      incidence of insulin resistance, defined as a fasting glucose/insulin ratio of
      <7, in the LGA/GDM group at 11 years. Analysis of insulin resistance at 11 years
      in a multivariate logistic regression revealed that childhood obesity and the
      combination of LGA status and maternal GDM were associated with insulin
      resistance, with odds ratios of 4.3 (95% confidence interval [CI]: 1.5-11.9) and
      10.4 (95% CI: 1.5-74.4), respectively. The prevalence at any time of > or =2
      components of MS was 50% for the LGA/GDM group, which was significantly higher
      than values for the LGA/control group (29%), AGA/GDM group (21%), and AGA/control
      group (18%). The prevalence of > or =3 components of MS at age 11 was 15% for the
      LGA/GDM group, compared with 3.0% to 5.3% for the other groups. Cox regression
      analysis was performed to determine the independent hazard (risk) of developing
      MS attributable to birth weight, gender, maternal prepregnancy obesity, and GDM.
      For Cox analyses, we defined MS as > or =2 of the following 4 components:
      obesity, hypertension (systolic or diastolic), glucose intolerance, and
      dyslipidemia (elevated triglyceride levels or low HDL levels). LGA status and
      maternal obesity increased the risk of MS approximately twofold, with hazard
      ratios of 2.19 (95% CI: 1.25-3.82) and 1.81 (95% CI: 1.03-3.19), respectively.
      GDM and gender were not independently significant. To determine the cumulative
      hazard of developing MS with time, we plotted the risk according to LGA or AGA
      category for the control and GDM groups from 6 years to 11 years, with Cox
      regression analyses. The risk of developing MS with time was not significantly
      different between LGA and AGA offspring in the control group but was
      significantly different between LGA and AGA offspring in the GDM group, with a
      3.6-fold greater risk among LGA children by 11 years. CONCLUSIONS: We showed that
      LGA offspring of diabetic mothers were at significant risk of developing MS in
      childhood. The prevalence of MS in the other groups was similar to the prevalence
      (4.8%) among white adolescents in the 1988-1994 National Health and Nutrition
      Examination Survey. This effect of LGA with maternal GDM on childhood MS was
      previously demonstrated for Pima Indian children but not the general population.
      We also found that children exposed to maternal obesity were at increased risk of
      developing MS, which suggests that obese mothers who do not fulfill the clinical
      criteria for GDM may still have metabolic factors that affect fetal growth and
      postnatal outcomes. Children who are LGA at birth and exposed to an intrauterine
      environment of either diabetes or maternal obesity are at increased risk of
      developing MS. Given the increased obesity prevalence, these findings have
      implications for perpetuating the cycle of obesity, insulin resistance, and their
      consequences in subsequent generations.

PMID- 15741355
TI  - The use of folk remedies among children in an urban black community: remedies for
      fever, colic, and teething.
AB  - BACKGROUND: Folk remedy use is universal, occurring in all cultures. Folk
      remedies have been and still are relied on in the black community. In this study,
      folk remedies refer to herbs, over-the-counter medications, and items
      traditionally used for cooking that are used to treat a variety of ailments.
      OBJECTIVE: To identify folk remedies used to treat fever, colic, and teething
      among black children in Detroit, Michigan. METHODS: Structured interviews were
      conducted with caregivers of healthy black children <2 years of age who were
      patients of the general pediatric clinic at Children's Hospital of Michigan.
      Descriptive analysis of the frequency distribution of the responses was
      performed. RESULTS: One hundred seven caregivers agreed to participate. All
      participants were familiar with the use of folk remedies. Most caregivers learned
      of these remedies from their mothers or grandmothers. Older parents were more
      likely to use folk remedies, but there was no difference in remedy use among
      different levels of maternal education. CONCLUSIONS: The knowledge and use of
      folk remedies were active in this black community. Their use seems to be
      cultural, rather than attributable to decreased access to health care. Physicians
      should be aware of these remedies, to educate families about remedies that may be
      harmful. Most remedies used pose no threat to health. In some cases, remedies may
      be blended with traditional medical treatments to ensure better patient
      compliance.

PMID- 15741356
TI  - Effects of seating position and appropriate restraint use on the risk of injury
      to children in motor vehicle crashes.
AB  - BACKGROUND: Currently, many states are upgrading their child restraint laws to
      include provisions for the use of age-appropriate restraints through 6 to 8 years
      of age, with some also requiring rear seating for children, enabling the laws to
      be in closer alignment with best-practice recommendations. OBJECTIVE: To evaluate
      the relationships of seating position and restraint status to the risk of injury
      among children in passenger vehicle crashes. METHODS: This was a cross-sectional
      study of children <16 years of age who were involved in crashes of insured
      vehicles in 15 states, with data collected via insurance claims records and a
      telephone survey. A probability sample of 17980 children in 11506 crashes,
      representing 229106 children in 146613 crashes, was collected between December 1,
      1998, and November 30, 2002. Parent reports were used to define restraint status,
      seating position, and occurrence of clinically significant injuries, with the use
      of a previously validated instrument. RESULTS: Approximately 62% of the children
      used seat belts, 35% used child restraints, and 3% used no restraint. Nearly 4 of
      5 children sat in the rear seat, with one half of all children being restrained
      appropriately for their age in the rear, although this varied according to the
      age of the child. Overall, 1.6% of children suffered serious injuries, 13.5% had
      minor injuries, and 84.9% did not have any injury. Unrestrained children in the
      front were at the highest risk of injury and appropriately restrained children in
      the rear were at the lowest risk, for all age groups. Inappropriately restrained
      children were at nearly twice the risk of injury, compared with appropriately
      restrained children (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.4
      2.3), whereas unrestrained children were at >3 times the risk (OR: 3.2; 95% CI:
      2.5-4.1). The effect of seating row was smaller than the effect of restraint
      status; children in the front seat were at 40% greater risk of injury, compared
      with children in the rear seat (OR: 1.4; 95% CI: 1.2-1.7). Had all children in
      the study population been appropriately restrained in the rear seat, 1014 serious
      injuries (95% CI: 675-1353 injuries) would have been prevented (with the
      assumption that restraint effectiveness does not depend on a variety of other
      driver-related, child-related, crash-related, vehicle-related, and environmental
      factors). CONCLUSIONS: Age-appropriate restraint confers relatively more safety
      benefit than rear seating, but the 2 work synergistically to provide the best
      protection for children in crashes. These results support the current focus on
      age-appropriate restraint in recently upgraded state child restraint laws.
      However, it is important to note that considerable added benefit would be
      realized with additional requirements for rear seating.

PMID- 15741357
TI  - Association of race/ethnicity with emergency department wait times.
AB  - OBJECTIVE: To determine whether wait times for children treated in emergency
      departments (EDs) nationally are associated with patient race/ethnicity. METHODS:
      Data were obtained from the National Hospital Ambulatory Medical Care Survey,
      which collects information on patient visits to EDs throughout the United States.
      We examined data for patients < or =15 years of age who presented to EDs during
      the 4-year period of 1997-2000. Sample weights were applied to the identified
      patient records to yield national estimates. For the purposes of this study,
      race/ethnicity was analyzed for 3 major groups, ie, non-Hispanic white (NHW), non
      Hispanic black (NHB), and Hispanic white (HW). RESULTS: During the 4-year study
      period, 20633 patient visits were surveyed, representing a national sample of
      92.9 million children < or =15 years of age. The race/ethnicity distribution
      included 9019 NHW children (59.5%), 3910 NHB children (23.9%), and 2991 HW
      children (16.6%). The wait time for all groups was 43.6 +/- 1.7 minutes (mean +/-
      SEM). There were significant unadjusted intergroup differences in wait times
      (38.5 +/- 1.6 minutes, 48.7 +/- 0.5 minutes, and 54.5 +/- 0.1 minutes for NHW,
      NHB, and HW children, respectively). Visit immediacy (triage status), when
      reported, was categorized as <15 minutes for 2203 children (17.1%), 15 to 60
      minutes for 5324 (41.4%), 1 to 2 hours for 3010 (25.1%), and >2 to 24 hours for
      1910 (16.4%). There were significant unadjusted differences in triage status
      according to race, with 14.6% of NHW patients being placed in the >2-hour
      immediacy range, compared with 18.8% of NHB patients and 20.0% of HW patients. In
      a linear regression analysis with logarithmically transformed wait time as a
      dependent variable and with adjustment for potential confounders, including
      hospital location, geographic region, and payer status, both NHB and HW patients
      waited longer than NHW patients, although the results were statistically
      significant only for HW patients. CONCLUSIONS: These nationally representative
      data suggest that children who come to EDs have wait times that vary according to
      race/ethnicity. There are several potential explanations for this observation,
      including discrimination, cultural incompetence, language barriers, and other
      social factors. These data and similar data from the National Hospital Ambulatory
      Medical Care Survey are useful in identifying nonclinical influences on the
      delivery of pediatric emergency care.

PMID- 15741358
TI  - National hospitalization impact of pediatric all-terrain vehicle injuries.
AB  - OBJECTIVE: All-terrain vehicle (ATV) injuries among children represent a
      significant and growing problem. Although state-level analyses have characterized
      some aspects of pediatric ATV-related injuries, little information on the
      national impact on hospitalization is available. This study was designed to
      characterize more fully the patterns of injury, hospital length of stay, and
      hospital charges associated with ATV-related injuries, with a nationally
      representative sample. METHODS: Analyses were based on the 1997 and 2000
      Healthcare Cost and Utilization Project Kids' Inpatient Database (KID). The KID
      is the only national, all-payer database of hospital discharges for children. KID
      data were weighted to represent all discharges from general hospitals in the
      United States. Discharges with external cause-of-injury codes consistent with off
      road ATV-related injuries were selected, and the affected population was
      described. Nationally representative rates of ATV-related injuries were
      calculated, and changes between 1997 and 2000 were documented. RESULTS: An
      estimated 5292 children were hospitalized because of ATV-related injuries during
      the 2-year period, and hospitalizations increased 79.1% between 1997 and 2000.
      Rates of ATV-related hospitalization were highest among adolescent white male
      subjects, consistent with previous studies. Most patients had hospital lengths of
      stay of <4 days (68%), but 10% had stays of >8 days. Injury severity varied
      considerably, with more than one third of patients sustaining moderate to severe
      injuries. Approximately 1% of hospitalizations resulted in in-hospital deaths.
      Total hospital charges for this injury mechanism were 74367677 dollars for the 2
      year study period. Most of these charges were paid by private insurers.
      CONCLUSIONS: This study provides evidence supporting recent substantial increases
      in childhood ATV-related injuries. The hospitalization impact of ATV-related
      injuries among children is considerable. Our data support the need for ongoing
      creative attempts to identify effective strategies to decrease ATV injuries among
      children.

PMID- 15741359
TI  - Epidemiologic features of the physical and sexual maltreatment of children in the
      Carolinas.
AB  - CONTEXT: Child maltreatment remains a significant public health and social
      problem in the United States. Incidence data rely on substantiated reports of
      maltreatment known to official social service agencies. OBJECTIVE: The objective
      of this study was to describe the epidemiologic features of child physical and
      sexual abuse, on the basis of maternal self-reports. DESIGN, SETTING, AND
      PARTICIPANTS: Computer-assisted, anonymous, cross-sectional, telephone surveys (N
      = 1435) were conducted with mothers of children 0 to 17 years of age in North and
      South Carolina. Mothers were asked about potentially abusive behaviors used by
      either themselves or their husbands or partners in the context of other
      disciplinary practices. They were also asked about their knowledge of any sexual
      victimization their children might have experienced. MAIN OUTCOME MEASURES: The
      incidence of physical and sexual maltreatment determined through maternal
      reports. RESULTS: Use of harsh physical discipline, equivalent to physical abuse,
      occurred with an incidence of 4.3%. Shaking of very young children as a means of
      discipline occurred among 2.6% of children <2 years of age. Mothers reported more
      frequent physical discipline of their children, including shaking, for themselves
      than for fathers or father figures. Nearly 11 of 1000 children were reported by
      their mothers as having been sexually victimized within the past year. The
      incidence of physical abuse determined with maternal self-reports was 40 times
      greater than that of official child physical abuse reports, and the sexual abuse
      incidence was 15 times greater. For every 1 child who sustains a serious injury
      as a result of shaking, an estimated 150 children may be shaken and go
      undetected. There was no statistically significant difference in the overall
      rates of physical or sexual maltreatment between the 2 states. CONCLUSIONS:
      Official statistics underestimate the burden of child maltreatment. Supplemental
      data obtained with alternative strategies can assist policymakers and planners in
      addressing needs and services within communities and states. These data support
      the need for continued interventions to prevent maltreatment.

PMID- 15741360
TI  - Characteristics of pediatric and adolescent patients attending a naturopathic
      college clinic in Canada.
AB  - OBJECTIVES: The use of complementary and alternative medicine (CAM) has grown
      substantially in North America and has drawn the attention of conventional
      medicine practitioners. Conventional-medicine practitioners have expressed
      concern about the potential for unregulated CAM therapies to cause harm, the
      sometimes-uncertain cost-benefit ratios associated with these therapies, and the
      possibility that some CAM providers might advise against established conventional
      therapies, such as vaccination. These concerns are heightened with respect to the
      pediatric use of CAM products. To address this issue, we conducted a systematic
      audit of pediatric and adolescent case files at a large, college-based, Canadian
      naturopathic teaching clinic. We specifically sought to describe the demographic
      characteristics, reasons for presentation, use of CAM products, and vaccinations
      status of children presenting for naturopathic assessment. We also determined
      factors associated with the use of CAM products and vaccination status. METHODS:
      We identified all charts for children (<18 years of age) who presented to the
      Robert Schad Naturopathic Clinic, the teaching clinic of the Canadian College of
      Naturopathic Medicine, between February 1 and May 31, 2002. Data were abstracted
      directly from the standardized patient intake forms and from clinical notes
      recorded during the patient's initial visit to the clinic. The following data
      were obtained: age, gender, chief presenting complaints reported by parents, CAM
      product use at presentation, vaccination status, and reactions to vaccination. We
      conducted logistic regression analyses to identify factors associated with both
      CAM product use and vaccination status. RESULTS: A total of 482 charts were
      identified. The mean age of patients was 6.5 years (95% confidence interval [CI]:
      1.6-11.4 years). The ratio of female subjects to male subjects was 1.09:1
      (248:227). The most common reasons for presentation were skin disorders (23%),
      gastrointestinal complaints (17%), and psychiatric/behavioral disorders (15%).
      Thirty-five percent of children were using CAM products at presentation (21.2%
      when both vitamins and minerals were excluded). Vitamins were the most commonly
      used products (34.6%), followed by herbal remedies (14.9%), oil blends/fats
      (7.2%), minerals (5.6%), probiotics (4.5%), and homeopathic remedies (3.7%). Of
      charts with vaccination information, 8.9% indicated that children had not been
      vaccinated; possible vaccine-associated adverse events were reported for 27% of
      those who had been vaccinated. Partial or unvaccinated status was associated with
      younger age, attending the Canadian College of Naturopathic Medicine for advice
      regarding vaccination, and greater use of CAM products. CAM product use was
      associated with unvaccinated or partially vaccinated status (odds ratio [OR]:
      2.86; 95% CI: 1.46-5.63), presenting with poor energy or fatigue (OR: 3.36; 95%
      CI: 1.00-11.26), or presenting with throat or sinus infections (OR: 4.06; 95% CI:
      1.23-13.04). CONCLUSIONS: Children present for naturopathic assessment for
      diverse reasons, are high-level consumers of CAM products, and have lower rates
      of vaccination than population averages. The conventional-medicine community
      should work with naturopaths to address public health concerns in this
      population.

PMID- 15741361
TI  - Changing conclusions on secondhand smoke in a sudden infant death syndrome review
      funded by the tobacco industry.
AB  - BACKGROUND: Prenatal and postnatal exposure to tobacco smoke adversely affects
      maternal and child health. Secondhand smoke (SHS) has been linked causally with
      sudden infant death syndrome (SIDS) in major health reports. In 1992, the US
      Environmental Protection Agency (EPA) first noted an association between SHS and
      SIDS, and both prenatal exposure and postnatal SHS exposure were listed as
      independent risk factors for SIDS in a 1997 California EPA report (republished in
      1999 by the National Cancer Institute) and a 2004 US Surgeon General report. The
      tobacco industry has used scientific consultants to attack the evidence that SHS
      causes disease, most often lung cancer. Little is known about the industry's
      strategies to contest the evidence on maternal and child health. In 2001, a
      review was published on SIDS that acknowledged funding from the Philip Morris
      (PM) tobacco company. Tobacco industry documents related to this review were
      examined to identify the company's influence on the content and conclusions of
      this review. METHODS: Tobacco industry documents include 40 million pages of
      internal memos and reports made available to the public as a result of litigation
      settlements against the tobacco industry in the United States. Between November
      2003 and January 2004, we searched tobacco industry document Internet sites from
      the University of California Legacy Tobacco Documents Library and the Tobacco
      Documents Online website. Key terms included "SIDS" and names of key persons. Two
      authors conducted independent searches with similar key terms, reviewed the
      documents, and agreed on relevancy through consensus. Thirty documents were
      identified as relevant. Two drafts (an early version and a final version) of an
      industry-funded review article on SIDS were identified, and 2 authors
      independently compared these drafts with the final publication. Formal comments
      by PM executives made in response to the first draft were also reviewed. We used
      Science Citation Index in July 2004 to determine citation patterns for the
      referenced SIDS reviews. RESULTS: PM executives feared that SHS and maternal and
      child health issues would create a powerful and emotional impetus for smoke-free
      areas in the home, public areas, and the workplace. In response to the 1992 US
      EPA report on SHS, the Science and Technology Department of PM's Switzerland
      subsidiary, Fabriques de Tabac Reunies, searched for "independent" consultants to
      publish articles addressing SHS. The first industry-funded article was a
      literature review focusing on smoking and SIDS, conducted by consultant Peter Lee
      and co-author Allison Thornton, which stated that the association between
      parental smoking and SIDS could have been attributable to the failure to control
      fully for confounders. That first review has only been cited once, in the
      subsequent industry-funded review. In 1997, PM commissioned a consultant, Frank
      Sullivan, to write a review, with coauthor Susan Barlow, of all possible risk
      factors for SIDS. The first draft concluded that prenatal and postnatal smoking
      exposures are both independent risk factors for SIDS. After receiving comments
      and meeting with PM scientific executives, Sullivan changed his original
      conclusions on smoking and SIDS. The final draft was changed to emphasize the
      effects of prenatal maternal smoking and to conclude that postnatal SHS effects
      were "less well established." Changes in the draft to support this new conclusion
      included descriptions of Peter Lee's industry-funded review, a 1999 negative but
      underpowered study of SIDS risk and urinary cotinine levels, and criticisms of
      the conclusions of the National Cancer Institute report that SHS was causally
      associated with SIDS. In April 2001, the Sullivan review was published in the
      United Kingdom journal Paediatric and Perinatal Epidemiology, with a disclosure
      statement that acknowledged financial support from PM but did not acknowledge
      contributions from PM executives in the preparation of the review. By 2004, the
      Sullivan SIDS review had been cited at least 19 times in the medical literature.
      CONCLUSIONS: PM executives responded to corporate concerns about the possible
      adverse effects of SHS on maternal and child health by commissioning consultants
      to write review articles for publication in the medical literature. PM executives
      successfully encouraged one author to change his original conclusion that SHS is
      an independent risk factor for SIDS to state that the role of SHS is "less well
      established." These statements are consistent with PM's corporate position that
      active smoking causes disease but only public health officials conclude the same
      for SHS. The author's disclosure of industry funding did not reveal the full
      extent of PM's involvement in shaping the content of the article. This analysis
      suggests that accepting tobacco industry funds can disrupt the integrity of the
      scientific process. The background of this SIDS review is relevant for
      institutions engaged in the debate about accepting or eschewing funding from the
      tobacco industry. Those who support acceptance of tobacco industry funds argue
      that academic authors retain the right to publish their work and maintain final
      approval of the written product, but this argument fails to recognize that the
      tobacco industry funds work to ensure that messages favorable to the industry are
      published and disseminated. Clinicians, parents, and public health officials are
      most vulnerable to the changed conclusions of the SIDS review. The national SIDS
      "Back to Sleep" campaign has been very successful in reducing SIDS rates.
      However, estimates of SIDS risk from SHS (odds ratios range from 1.4 to 5.1) have
      considerable overlap with estimates of risk from prone sleep positioning (odds
      ratios range from 1.7 to 12.9). With the Back to Sleep campaign well underway,
      efforts to address parental smoking behavior in both the prenatal and postnatal
      periods should be intensified. The tobacco industry's disinformation campaign on
      SHS and maternal and child health can be counteracted within clinicians' offices.

PMID- 15741362
TI  - "Binkie flutter," an apparently voluntary behavior of infants, possibly related
      to vibratory jaw movements in dogs: report of 4 cases.
AB  - Four cases of apparently voluntary rapid vibratory pacifier movements occurring
      in normal, unstressed infants up to 1 year of age and captured on video are
      presented. I speculate on the possible relationship of the movements to similar
      vibratory jaw movements in dogs, in which species they may represent a
      neuromuscular mechanism for rapid feedback control.

PMID- 15741363
TI  - Chronic abdominal pain in children.
AB  - Chronic abdominal pain, defined as long-lasting intermittent or constant
      abdominal pain, is a common pediatric problem encountered by primary care
      physicians, medical subspecialists, and surgical specialists. Chronic abdominal
      pain in children is usually functional, that is, without objective evidence of an
      underlying organic disorder. The Subcommittee on Chronic Abdominal Pain of the
      American Academy of Pediatrics and the North American Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition has prepared this report based on a
      comprehensive, systematic review and rating of the medical literature. This
      report accompanies a clinical report based on the literature review and expert
      opinion. The subcommittee examined the diagnostic and therapeutic value of a
      medical and psychological history, diagnostic tests, and pharmacologic and
      behavioral therapy. The presence of alarm symptoms or signs (such as weight loss,
      gastrointestinal bleeding, persistent fever, chronic severe diarrhea, and
      significant vomiting) is associated with a higher prevalence of organic disease.
      There was insufficient evidence to state that the nature of the abdominal pain or
      the presence of associated symptoms (such as anorexia, nausea, headache, and
      joint pain) can discriminate between functional and organic disorders. Although
      children with chronic abdominal pain and their parents are more often anxious or
      depressed, the presence of anxiety, depression, behavior problems, or recent
      negative life events does not distinguish between functional and organic
      abdominal pain. Most children who are brought to the primary care physician's
      office for chronic abdominal pain are unlikely to require diagnostic testing.
      Pediatric studies of therapeutic interventions were examined and found to be
      limited or inconclusive.

PMID- 15741364
TI  - Annual summary of vital statistics--2003.
AB  - The crude birth rate rose slightly in 2003 to 14.1 births per 1000 population,
      from 13.9 in 2002. The 2002 rate was the lowest ever reported for the United
      States. The total number of births and the fertility rate (66.1) also increased.
      The birth rate for teenaged mothers dropped 3% to another record low in 2003, to
      41.7 per 1000 females aged 15 to 19 years. The teenage birth rate has fallen by
      one third since 1991. The birth rate declined for women 20 to 24 years old but
      rose for women aged 25 to 44 years. The number, rate, and proportion of births to
      unmarried women all increased in 2003. Smoking during pregnancy declined to 11%,
      down from 19.5% in 1989. Prenatal care utilization improved slightly for 2003;
      84.1% of women began care in the first trimester of pregnancy. The cesarean
      delivery rate jumped 6% to 27.6% for another US high. The primary cesarean rate
      rose 6%, and the rate of vaginal birth after a previous cesarean delivery
      plummeted 16% from 2002 to 2003. The percent of infants delivered preterm
      continued to rise (12.3% in 2003). The preterm birth rate is up 16% since 1990.
      The percentage of children born at low birth weight rose slightly in 2003 to the
      highest level reported since 1970 (7.9%). The twinning rate increased, but the
      rate for triplet/+ births declined slightly between 2001 and 2002. Multiple
      births accounted for 3.3% of all births in 2002. The infant mortality rate rose
      to 7.0/1000 live births in 2002 from 6.8 in 2001, marking the first increase in
      this rate in >4 decades. Increases were distributed fairly widely across age,
      racial/ethnic groups, and geographic areas. The rise in infant mortality was
      attributed to increases in <750-g births in both singleton and multiple
      deliveries. Although the downward trend in infant mortality rates in many
      developed nations may have stabilized, the United States still ranked 27th among
      these nations in 2001. Expectation of life at birth reached a record high of 77.3
      years for all gender and race groups combined in 2002. Death rates in the United
      States continue to decline. Between 2001 and 2002, death rates declined for the 3
      leading causes of death: diseases of heart, malignant neoplasms, and
      cerebrovascular diseases. Death rates for children 1 to 19 years old decreased by
      8% for suicide; the death rate for chronic lower respiratory diseases increased
      by 33% in 2002. Rates for unintentional injuries and homicide did not change
      significantly for children aged 1 to 19 years. A large proportion of childhood
      deaths continues to occur as a result of preventable injuries.

PMID- 15741365
TI  - Provider and practice characteristics associated with antibiotic use in children
      with presumed viral respiratory tract infections.
AB  - OBJECTIVE: Although overuse of antibiotics in children has been well documented,
      relatively little information is known about provider and facility
      characteristics associated with this prescribing practice. This study was done to
      evaluate the differences in overuse of antibiotics among staff physicians and
      resident/interns (housestaff [HS]) who work in hospital-based outpatient clinics.
      METHODS: This cross-sectional study involved patient encounters in outpatient
      departments that were included in the US National Hospital Ambulatory Medical
      Care Survey database from 1995 to 2000. Encounters with patients who were aged
      <18 years and had a primary diagnosis suggestive of viral respiratory tract
      infection were evaluated. Patients with comorbid conditions that might justify
      antibiotic use were excluded. RESULTS: This study included 1952 patient
      encounters with a primary diagnosis suggestive of a viral infection and 33.2% of
      these patients receiving antibiotics. Overall, antibiotic use was significantly
      less among HS (19.5%) than staff physicians (36.4%; odds ratio [OR]: 0.44; 95%
      confidence interval [CI]: 0.33-0.59). This difference between HS (19.5%) and
      staff physicians (32.5%) persisted even within teaching hospitals (OR: 0.5; 95%
      CI: 0.4-0.7). Among staff physicians, antibiotic use was greater among those who
      work in nonteaching (39.6%) compared with teaching hospitals (32.5%; OR: 1.51;
      95%: CI 1.15-1.98). Controlling for other patient and provider variables,
      antibiotic use occurred less among HS than among staff physicians in teaching
      hospitals (OR: 0.53; 95% CI: 0.38-0.75). CONCLUSIONS: Antibiotic prescribing in
      the context of an outpatient visit for a diagnosis suggestive of a viral
      respiratory tract illness occurs more commonly among staff physicians than
      trainees and among staff physicians more commonly in nonteaching compared with
      teaching institutions.

PMID- 15741367
TI  - Does melanoma behave differently in younger children than in adults? A
      retrospective study of 33 cases of childhood melanoma from a single institution.
AB  - OBJECTIVE: To ascertain whether childhood melanoma presents any peculiar clinical
      features or differences in prognosis with respect to adults, we retrospectively
      analyzed the data from 33 patients who were up to 14 years of age and treated for
      cutaneous melanoma at the Istituto Nazionale Tumori, Milan, over a 25-year
      period. METHODS: Primary lesions were amelanotic in half of the cases and raised
      in 73%. Lower extremities were the most common primary sites. Histologically, 9
      cases were classified as nodular type, and median thickness was 2.5 mm. Nine
      children had nodal involvement at diagnosis, 2 in-transit metastases, and 1
      distant spread. Surgery was the mainstay of treatment; 9 patients underwent lymph
      node dissection, 3 received chemotherapy, and 2 received radiotherapy. RESULTS:
      With a median follow-up of 122 months, 5-year event-free survival and overall
      survival were 60% and 70%, respectively. Age seemed to correlate with survival,
      event-free survival being 90% in children under 10 and 47% in older patients,
      although the initial microstaging seemed worse in the former. CONCLUSION: By
      comparison with adult cases, childhood melanoma can have a higher percentage of
      atypical clinical features (amelanotic and raised lesions), nodular histotype,
      and thick lesions. Although we have no data to support any suggestion of
      biological differences between young children and adolescents or adults, our
      findings give the impression that melanoma behaves differently in the younger age
      group.

PMID- 15741366
TI  - Severe Staphylococcal sepsis in adolescents in the era of community-acquired
      methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: More than 70% of the community-acquired (CA) staphylococcal infections
      treated at Texas Children's Hospital are caused by methicillin-resistant
      Staphylococcus aureus (MRSA). Since September 2002, an increase in the number of
      severely ill patients with S aureus infections has occurred. This study provides
      a clinical description of severely ill adolescent patients and an analysis of
      their isolates using molecular methods. METHODS: We identified adolescent
      patients meeting criteria for severe sepsis requiring admission to the PICU.
      Patient records were reviewed, and isolates were obtained for susceptibility
      testing and DNA extraction. Isolates were tested for the presence of virulence
      genes (cna, tst, lukS-PV, and lukF-PV) and enterotoxin genes (sea, seb, sec, sed,
      seh, and sej) by polymerase chain reaction. Genomic fingerprints were determined
      by repetitive-element polymorphism polymerase chain reaction and pulse-field gel
      electrophoresis. SCCmec cassette type was determined. RESULTS: Fourteen
      adolescents with severe CA S aureus infections were identified between August
      2002 and January 2004. All were admitted to the PICU with sepsis and
      coagulopathy. Twelve patients had CA-MRSA infections; 2 had CA methicillin
      susceptible Staphylococcus aureus (MSSA) infections. The mean age was 12.9 years
      (range: 10-15 years). Thirteen patients had pulmonary involvement and/or bone and
      joint infection; 10 patients had > or =2 bones or joints infected (range: 2-10);
      4 patients developed vascular complications (deep venous thrombosis); and 3
      patients died. All isolates were identical or closely related to the previously
      reported predominant clone in Houston, Texas (multilocus sequence type 8,
      USA300), and carried lukS-PV and lukF-PV genes as well as the SCCmec type IVa
      cassette (12 MRSA isolates) but did not contain cna or tst. Only 1 strain carried
      enterotoxin genes (sed and sej). CONCLUSIONS: Severe staphylococcal infections in
      previously healthy adolescents without predisposing risk factors have presented
      more frequently at Texas Children's Hospital since September 2002. CA MRSA and
      clonally related CA MSSA characterized as USA300 and sequence type 8 have been
      isolated from these patients.

PMID- 15741368
TI  - Impact of postnatal systemic corticosteroids on mortality and cerebral palsy in
      preterm infants: effect modification by risk for chronic lung disease.
AB  - OBJECTIVE: In preterm infants, chronic lung disease (CLD) is associated with an
      increased risk for cerebral palsy (CP). However, systemic postnatal
      corticosteroid therapy to prevent or treat CLD, although effective in improving
      lung function, may cause CP. The objective of this study was to determine the
      effect of systemic postnatal corticosteroid treatment on death and CP and to
      assess any modification of effect arising from risk for CLD. METHODS: Randomized,
      controlled trials of postnatal corticosteroid therapy for prevention or treatment
      of CLD in preterm infants that reported rates of both mortality and CP were
      reviewed and their data were synthesized. Twenty studies with data on 1721
      randomized infants met eligibility criteria. The relationship between the
      corticosteroid effect on the combined outcome, death or CP, and the risk for CLD
      in control groups was analyzed by weighted meta-regression. RESULTS: Among all
      infants who were randomized, a significantly higher rate of CP after
      corticosteroid treatment (typical risk difference [RD]: 0.05; 95% confidence
      interval [CI]: 0.02, 0.08) was partly offset by a nonsignificant reduction in
      mortality (typical RD: -0.02; 95% CI: -0.06 to 0.02). Consequently, there was no
      significant effect of corticosteroid treatment on the combined rate of mortality
      or CP (typical RD: 0.03; 95% CI: -0.01 to 0.08). However, on meta-regression,
      there was a significant negative relationship between the treatment effect on
      death or CP and the risk for CLD in control groups. With risks for CLD below 35%,
      corticosteroid treatment significantly increased the chance of death or CP,
      whereas with risks for CLD exceeding 65%, it reduced this chance. CONCLUSIONS:
      The effect of postnatal corticosteroids on the combined outcome of death or CP
      varies with the level of risk for CLD.

PMID- 15741369
TI  - Home use of the GlucoWatch G2 biographer in children with diabetes.
AB  - OBJECTIVE: To evaluate usability, accuracy, and hypoglycemia detection of the
      GlucoWatch G2 Biographer (GW2B) in children aged 1 to 17 years. METHODS: After a
      15-hour study of device accuracy, 46 children (15 <7 years, 31 > or =7 years)
      with type 1 diabetes were enrolled for an extended-wear outcome study: 2 daytime
      and 2 nighttime 15-hr wear periods each week and blood glucose monitoring 4 times
      daily for 3 months. RESULTS: A total of 531 paired GW2B/meter readings were
      available for accuracy assessment. The correlation coefficients were 0.58 and
      0.74 (ages <7 and > or =7 years, respectively). There was no significant change
      in hemoglobin A1C)or weight-adjusted insulin dose at 3 months after biographer
      use. Forty-two episodes of hypoglycemia were detected by the GW2B, 33 of which
      were confirmed by blood glucose meters. Sensitivity and specificity of audible
      low-glucose alerts were approximately 79% and 83%, respectively. No significant
      side effects were reported. CONCLUSION: The GW2B is usable and safe in children
      who are <7 years or older in the home setting. The GW2B can detect asymptomatic
      nocturnal hypoglycemia in younger children.

PMID- 15741370
TI  - A rose by any other name? Objective knowledge, perceived knowledge, and
      adolescent male condom use.
AB  - OBJECTIVE: To investigate the role of objective and perceived knowledge about
      condoms in adolescent males' condom use at first intercourse. METHODS: A
      longitudinal analysis was conducted of data from a nationally representative
      sample of 404 virgin male adolescents who were aged 15 to 17 years at wave 1 and
      reported becoming sexually experienced at the second wave of data collection.
      Objective knowledge was measured as a 5-item knowledge test about condoms.
      Perceived knowledge was measured as a 5-item scale regarding participants'
      confidence about their answers on the objective knowledge test. Condom use was
      assessed by self-report. RESULTS: Objective and perceived knowledge were
      moderately correlated with each other. Male adolescents with low objective but
      high perceived knowledge were identified as being at particular risk for not
      using a condom in that they were nearly 3 times less likely to report using a
      condom at first intercourse (odds ratio: 0.35) than those with other levels of
      objective and perceived knowledge. CONCLUSIONS: Previous evidence suggests that
      knowledge about sex does not accurately predict sexual behavior. This lack of
      predictive accuracy may be because studies have focused only on objective
      knowledge. Our results suggest that both objective and perceived knowledge serve
      as antecedents to male condom use at first intercourse. However, those with
      higher perceived knowledge, particularly in the context of low objective
      knowledge, may be at greater risk for not using condoms. Addressing not only
      objective but also perceived knowledge may increase the effectiveness of
      interventions that are designed to increase rates of condom use among male
      adolescents.

PMID- 15741371
TI  - Adverse neurodevelopmental outcomes among extremely low birth weight infants with
      a normal head ultrasound: prevalence and antecedents.
AB  - OBJECTIVE: Severe abnormalities of the head ultrasound (HUS) are important
      predictors of cerebral palsy (CP) and mental retardation, and a normal HUS
      usually ensures the absence of major impairments. With the increasing survival of
      extremely low birth weight (ELBW) infants (birth weight <1000 g), the prognostic
      significance of a normal HUS may differ. This study examined the prevalence of
      and risk factors for CP and impaired mental development among ELBW infants with a
      normal HUS. METHODS: Study infants were ELBW infants who were cared for in
      Neonatal Research Network centers in the years 1995-1999, had a normal early and
      late HUS, survived to discharge, and returned for follow-up assessments at 18 to
      22 months' corrected age. The outcomes of interest were a score <70 on the Bayley
      Scales of Infant Development-II Mental Developmental Index (MDI) and CP. Risk
      factors included maternal demographics; infant characteristics; and interventions
      or morbidities related to the lung, infection, and nutrition. Logistic regression
      was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A time
      oriented approach was used to select variables for inclusion in logistic models.
      RESULTS: Of 1749 infants with a normal early and late HUS (performed at a mean
      age of 6 and 47 days, respectively), 1473 (84%) returned for follow-up
      assessment. Infants had a birth weight of 792 +/- 134 g (mean +/- SD) and
      gestational age of 26 +/- 2 weeks. Rates of CP and MDI <70 were 9.4% and 25.3%,
      respectively, and 29.2% of infants had either CP or MDI <70. In multivariate
      analyses, factors associated with CP were male gender (OR: 1.8; 95% CI: 1.2-2.6),
      multiple birth, (OR: 1.6; 95% CI: 1.1-2.5), decreasing birth weight (OR: 1.3 for
      each 100-g decrease; 95% CI: 1.1-1.5), pneumothorax (OR: 2.3; 95% CI: 1.2-4.4),
      and days of conventional ventilation (OR: 1.2 for each additional 10 days; 95%
      CI: 1.1-1.3). With the exception of pneumothorax, these same factors were
      associated with MDI <70, in addition to less maternal education (OR: 1.4; 95% CI:
      1.0-1.9) and Medicaid or lack of coverage for maternal insurance (OR: 1.7; 95%
      CI: 1.2-2.4). CONCLUSIONS: Nearly 30% of ELBW infants with a normal HUS had
      either CP or a low MDI. Risk factors that are associated with this high rate of
      adverse outcomes include pneumothorax, prolonged exposure to mechanical
      ventilation, and educational and economic disadvantage. Improvements in pulmonary
      care to reduce duration of ventilation and avoid air leaks might improve
      neurodevelopmental outcome for ELBW infants.

PMID- 15741372
TI  - Follow-up at 15 years of preterm infants from a controlled trial of moderately
      early dexamethasone for the prevention of chronic lung disease.
AB  - OBJECTIVE: Postnatal dexamethasone treatment of ventilator-dependent preterm
      infants results in rapid improvement in lung function and reduction in chronic
      lung disease. However, limited data are available on long-term outcomes after
      such therapy. We studied growth, neurodevelopmental, and pulmonary outcomes at
      adolescence in children who had participated in a double-blind, placebo
      controlled trial of dexamethasone beginning at 2 weeks of age for the prevention
      of chronic lung disease. METHODS: Thirty-six infants (birth weight < or =1250 g
      and gestational age < or =30 weeks) who were dependent on mechanical ventilation
      at 2 weeks of age received a 42-day course of dexamethasone, an 18-day course of
      dexamethasone, or saline placebo. Twenty-two children survived to 15 years (69%
      of the 42-day dexamethasone group, 67% of the 18-day dexamethasone group and 45%
      of the control group), and all were evaluated. Intact survival was defined as
      survival with normal neurologic examination, IQ >70, and receiving education in
      the regular classroom. RESULTS: There were no differences among groups for growth
      or incidence of neurologic abnormalities. The mean IQ for the 42-day
      dexamethasone group was 85 +/- 10 compared with 60 +/- 20 for the 18-day
      dexamethasone group and 73 +/- 23 for the control group. All children in the 42
      day dexamethasone group were receiving education in the regular classroom
      compared with only 50% of the 18-day dexamethasone group and 40% of the control
      group. As a result, intact survival was significantly greater for the 42-day
      dexamethasone group (69%) than for either the 18-day dexamethasone group (25%) or
      the control group (18%). Pulmonary function was significantly better for the 42
      day dexamethasone group compared with the 18-day dexamethasone group (eg, forced
      expiratory volume in 1 second: 90 +/- 16 vs 71 +/- 15% predicted, respectively).
      CONCLUSION: A 42-day course of dexamethasone therapy beginning at 2 weeks of age
      in preterm infants who are at high risk for severe chronic lung disease was
      associated with improved long-term neurodevelopmental outcome. Although
      additional research is needed to establish the optimal steroid preparation,
      dosage, and duration of therapy, these data support the view that moderately
      early (beginning at 1-2 weeks) corticosteroid treatment is advantageous for a
      select group of ventilator-dependent preterm infants.

PMID- 15741373
TI  - Late gestation cerebellar growth is rapid and impeded by premature birth.
AB  - OBJECTIVE: Cognitive impairments and academic failure are commonly reported in
      survivors of preterm birth. Recent studies suggest an important role for the
      cerebellum in the development of cognitive and social functions. The objective of
      this study was to examine the impact of prematurity itself, as well as
      prematurity-related brain injuries, on early postnatal cerebellar growth with
      quantitative MRI. METHODS: Advanced 3-dimensional volumetric MRI was performed
      and cerebellar volumes were obtained by manual outlining in preterm (<37 weeks)
      and healthy term-born infants. Intracranial and total brain volumes were also
      calculated. RESULTS: A total of 169 preterm and 20 healthy full-term infants were
      studied; 145 had preterm MRI (pMRI), 75 had term MRI (tMRI), and 51 underwent
      both pMRI and tMRI. From 28 weeks' postconceptional age to term, mean cerebellar
      volume (177%) in preterm infants increased at a much faster rate than did mean
      intracranial (110%) or mean brain (107%) volumes. Smaller cerebellar volume was
      significantly related to lower gestational age at birth and to intracranial and
      total brain volumes. Mean cerebellar volume of preterm infants at tMRI was
      significantly smaller than the volumes of term-born infants. Cerebellar growth
      impairment was correlated strongly with associated brain injuries, even in the
      absence of direct cerebellar injury. CONCLUSIONS: Our data suggest that the
      growth of the immature cerebellum is particularly rapid during late gestation.
      However, this accelerated growth seems to be impeded by premature birth and
      associated brain injury. The long-term neurodevelopmental disabilities seen in
      survivors of premature birth may be attributable in part to impaired cerebellar
      development.

PMID- 15741375
TI  - No license required: severe pediatric motorbike-related injuries in Ohio.
AB  - OBJECTIVE: Motorbikes (MBs), including motorcycles and dirt bikes, are becoming
      increasingly popular among children and adolescents. MBs are intended for off
      road use. Although children who are younger than 16 years cannot be licensed to
      drive cars, they can drive MBs off-road without licenses. The objective of this
      study was to determine the epidemiology of severe MB injuries to children who are
      younger than 16 years in Ohio. METHODS: Eight hospitals that admit the majority
      of pediatric trauma patients in Ohio were approached to participate. Cases were
      identified using hospital trauma registries and were defined as any hospitalized
      child who was younger than 16 years and sustained MB injuries between January 1,
      1995, and December 31, 2001. RESULTS: Six hospitals participated. A total of 182
      children were hospitalized with a mean age of 11.4 years (range: <1-15 years). A
      total of 89.6% were male, 89.0% were white, 68.7% had commercial medical
      insurance, and 71.4% were from urban areas. From 1995 to 1997, there were an
      average of 20 annual admissions; however, from 1998 to 2001, there were an
      average of 30 per year. Of the 85% of patients with injury events documented,
      35.5% were riding in streets and 53.3% were unhelmeted. One patient died; 8
      required rehabilitation. The mean injury severity score was 9.9 (median: 9), and
      mean length of hospitalization was 4.6 days (median: 3). Unhelmeted riders had
      significantly higher injury severity scores than helmeted ones (11.5 vs 8.4). The
      difference in mean length of hospitalization of unhelmeted compared with helmeted
      riders approached statistical significance (6.1 vs 3.7 days). Of the 163 patients
      with documented diagnoses, there were 510 injuries; 68.7% of patients sustained
      multiple injuries. Of all injuries, the most commonly injured body parts were
      lower extremity (23.4%), head (22.2%), abdomen/pelvis (13.4%), upper extremity
      (12.4%), and face (11.8%). The most common injuries were fractures (37.1%),
      abrasions/contusions (24.4%), lacerations (13.4%), intracranial injuries (7.5%),
      and solid abdominal organ injuries (7.5%). Central and Southwest Ohio had higher
      numbers of hospitalized injuries than other areas. CONCLUSION: Urban, white boys
      with commercial medical insurance predominated among children with MB-related
      injuries in Ohio. Most injured children did not wear a helmet and sustained
      multiple injuries. Not wearing a helmet resulted in significantly increased
      injury severity and a trend toward increased lengths of stay in the hospital. MB
      related injuries increased by approximately 50% during the study period. Children
      should not operate MBs until they are old enough to obtain a motor vehicle
      driver's license, which occurs at a minimum of 16 years of age. High-risk
      populations need to be targeted to reduce these injuries, and requiring helmet
      use while operating MBs should be pursued.

PMID- 15741374
TI  - Neurodevelopmental and growth outcomes of extremely low birth weight infants
      after necrotizing enterocolitis.
AB  - OBJECTIVES: Necrotizing enterocolitis (NEC) is a significant complication for the
      premature infant. However, subsequent neurodevelopmental and growth outcomes of
      extremely low birth weight (ELBW) infants with NEC have not been well described.
      We hypothesized that ELBW infants with surgically managed (SurgNEC) are at
      greater risk for poor neurodevelopmental and growth outcomes than infants with
      medically managed NEC (MedNEC) compared with infants without a history of NEC
      (NoNEC). The objective of this study was to compare growth, neurologic, and
      cognitive outcomes among ELBW survivors of SurgNEC and MedNEC with NoNEC at 18 to
      22 months' corrected age. METHODS: Multicenter, retrospective analysis was
      conducted of infants who were born between January 1, 1995, and December 31,
      1998, and had a birth weight <1000 g in the National Institute of Child Health
      and Human Development Neonatal Research Network Registry. Neurodevelopment and
      growth were assessed at 18 to 22 months' postmenstrual age. chi2, t test, and
      logistic regression analyses were used. RESULTS: A total of 2948 infants were
      evaluated at 18 to 22 months, 124 of whom were SurgNEC and 121 of whom were
      MedNEC. Compared with NoNEC, both SurgNEC and MedNEC infants were of lower birth
      weight and had a greater incidence of late sepsis; SurgNEC but not MedNEC infants
      were more likely to have received a diagnosis of cystic periventricular
      leukomalacia and bronchopulmonary dysplasia and been treated with postnatal
      steroids. Weight, length, and head circumference <10 percentile at 18 to 22
      months were significantly more likely among SurgNEC but not MedNEC compared with
      NoNEC infants. After correction for anthropometric measures at birth and adjusted
      age at follow-up, all growth parameters at 18 to 22 months for SurgNEC but not
      MedNEC infants were significantly less than for NoNEC infants. SurgNEC but not
      MedNEC was a significant independent risk factor for Mental Developmental Index
      <70 (odds ratio [OR]: 1.61; 95% confidence interval [CI]: 1.05-2.50), Psychomotor
      Developmental Index <70 (OR: 1.95; 95% CI: 1.25-3.04), and neurodevelopmental
      impairment (OR: 1.78; 95% CI: 1.17-2.73) compared with NoNEC. CONCLUSIONS: Among
      ELBW infants, SurgNEC is associated with significant growth delay and adverse
      neurodevelopmental outcomes at 18 to 22 months' corrected age compared with
      NoNEC. MedNEC does not seem to confer additional risk. SurgNEC is likely to be
      associated with greater severity of disease.

PMID- 15741376
TI  - Retrospective review of serious bacterial infections in infants who are 0 to 36
      months of age and have influenza A infection.
AB  - OBJECTIVE: Previous studies of febrile children who were 3 to 36 months of age
      and had clinically recognizable viral syndromes have shown low rates of
      concurrent bacteremia. We sought to determine the prevalence of serious bacterial
      infections (SBIs) among children with influenza A, a viral syndrome that can be
      established definitively by specific tests. METHODS: We performed a retrospective
      cross-sectional study of patients who were 0 to 36 months of age and presented
      with fever to the emergency department (ED) over 4 consecutive influenza seasons.
      Chest radiographs and urine and cerebrospinal fluid cultures also were reviewed.
      RESULTS: Of 705 included patients, 163 (23%) were influenza positive (IP) and 542
      (77%) were influenza negative (IN). Only 1 IP patient was bacteremic (0.6%)
      versus 23 of the 542 IN control subjects (4.2%). Two (1.8%) of 110 IP cases had
      urinary tract infections versus 38 (9.9%) of the 382 IN control subjects.
      Thirteen (25.4%) of 51 IP patients had radiographic evidence of pneumonia versus
      99 (41.9%) of 236 IN control subjects. There were no cases of meningitis in 41
      cerebrospinal fluid samples obtained from IP patients versus 4 (2.2%) cases of
      culture-positive meningitis in 179 IN control subjects. A total of 16 (9.8%) SBIs
      were identified in the IP cases versus 153 (28.2%) in the IN control subjects.
      CONCLUSIONS: Febrile children with influenza A had a lower prevalence of
      bacteremia, urinary tract infections, consolidative pneumonia, or any SBI
      compared with those without influenza A infection in this study.

PMID- 15741377
TI  - Physician and dentist tobacco use counseling and adolescent smoking behavior:
      results from the 2000 National Youth Tobacco Survey.
AB  - OBJECTIVE: The present study describes patterns of tobacco use counseling among
      physicians and dentists as reported by adolescents and determines the association
      between provider advice to quit and cessation activities among current smokers.
      METHODS: Data were analyzed from the 2000 National Youth Tobacco Survey, an
      anonymous, self-administered, school-based survey. The National Youth Tobacco
      Survey was administered to a nationally representative sample of 35828 students
      in grades 6 to 12 in 324 schools. RESULTS: Thirty-three percent of adolescents
      who visited a physician or a dentist in the past year reported that a physician
      counseled them about the dangers of tobacco use, and 20% reported that a dentist
      provided a similar message. Among students who smoked in the past year, 16.4%
      received advice to quit from a physician and 11.6% received advice to quit from a
      dentist. Physician or dentist advice to quit was correlated with 1 or more quit
      attempts in the past 12 months. CONCLUSION: On the basis of adolescent reports,
      physician and dentist practice patterns remain well below recommended guidelines.
      Results suggest that provider advice to quit is associated with cessation
      activity. Additional studies are needed to confirm whether the low prevalence of
      brief provider tobacco use counseling is a missed opportunity to affect
      adolescent smoking behavior.

PMID- 15741378
TI  - Asthma phenotypes, risk factors, and measures of severity in a national sample of
      US children.
AB  - OBJECTIVE: To examine a nationally representative sample of US children aged 6 to
      16 years old and determine whether there are differences in risk factors and
      measures of severity between children with different asthma phenotypes. METHODS:
      We analyzed data from the Third National Health and Nutrition Examination Survey.
      We used questionnaire and skin-prick testing data to separate children into the
      following mutually exclusive categories: atopic asthma, nonatopic asthma,
      resolved asthma, frequent respiratory symptoms with no asthma diagnosis, and
      normal. We used multivariate regression to determine whether demographic or
      potential risk factors varied between phenotypes and whether measures of severity
      varied by phenotype. RESULTS: We found that 4.8% of children had atopic asthma,
      1.9% had nonatopic asthma, 3.4% had resolved asthma, and 4.3% had frequent
      respiratory symptoms. Risk factors varied by phenotype, for example, the mean BMI
      was higher among children with nonatopic asthma, prenatal maternal smoking was a
      risk factor for resolved asthma, and child care attendance was a risk factor for
      frequent respiratory symptoms with no asthma diagnosis. Patients with atopic and
      nonatopic asthma were similar for most measures of asthma severity (medication
      use, health status, and lung function impairment). In contrast, patients with
      resolved asthma had fewer symptoms but a similar level of lung function
      impairment to that seen in patients with current asthma, whereas children with
      frequent respiratory symptoms but no asthma diagnosis had normal lung function.
      CONCLUSIONS: Asthma risk factors and measures of severity vary between children
      with different asthma phenotypes.

PMID- 15741379
TI  - Association between fetal lymphedema and congenital cardiovascular defects in
      Turner syndrome.
AB  - OBJECTIVES: Turner syndrome (TS) is associated with congenital cardiovascular
      defects (CCVDs), most commonly bicuspid aortic valve (BAV) and aortic coarctation
      (COARC), congenital renal anomalies, and fetal lymphedema. It has been theorized
      that compressive or obstructive effects of fetal lymphedema may actually cause
      cardiovascular and renal dysmorphogenesis in TS. The objective of this study was
      to determine whether there is a specific association between a history of fetal
      lymphedema and CCVDs in monosomy X, or TS, independent of karyotype or general
      severity of the phenotype. METHODS: This was a prospective study of 134 girls and
      women who have TS (mean age: 30 years) and were clinically evaluated for evidence
      of fetal lymphedema, classified as central (signified by the presence of neck
      webbing) or peripheral (current or perinatal, or dysplastic fingernails). The
      presence of BAV and/or COARC was detected by magnetic resonance imaging combined
      with echocardiography, and renal anomalies were determined by ultrasound.
      RESULTS: There is a strong association between developmental central lymphedema,
      signified by neck webbing, and the presence of BAV (chi2 = 10) and COARC (chi2 =
      8). The association between webbed neck and CCVDs was independent of karyotype.
      There was, in contrast, no significant association between renal anomalies and
      webbed neck or CCVDs. CONCLUSIONS: The strong, statistically significant
      association between neck webbing and the presence of BAV and COARC in TS suggests
      a pathogenetic connection between fetal lymphatic obstruction and defective
      aortic development. The presence of neck webbing in TS should alert the clinician
      to the possibility of congenital cardiovascular defects.

PMID- 15741380
TI  - Calcium, dairy products, and bone health in children and young adults: a
      reevaluation of the evidence.
AB  - OBJECTIVE: Numerous nutrition policy statements recommend the consumption of 800
      to 1500 mg of calcium largely from dairy products for osteoporosis prevention;
      however, the findings of epidemiologic and prospective studies have raised
      questions about the efficacy of the use of dairy products for the promotion of
      bone health. The objective of this study was to review existing literature on the
      effects of dairy products and total dietary calcium on bone integrity in children
      and young adults to assess whether evidence supports (1) current recommended
      calcium intake levels and (2) the suggestion that dairy products are better for
      promoting bone integrity than other calcium-containing food sources or
      supplements. METHODS: A Medline (National Library of Medicine, Bethesda, MD)
      search was conducted for studies published on the relationship between milk,
      dairy products, or calcium intake and bone mineralization or fracture risk in
      children and young adults (1-25 years). This search yielded 58 studies: 22 cross
      sectional studies; 13 retrospective studies; 10 longitudinal prospective studies;
      and 13 randomized, controlled trials. RESULTS: Eleven of the studies did not
      control for weight, pubertal status, and exercise and were excluded. Ten studies
      were randomized, controlled trials of supplemental calcium, 9 of which showed
      modest positive benefits on bone mineralization in children and adolescents. Of
      the remaining 37 studies of dairy or unsupplemented dietary calcium intake, 27
      studies found no relationship between dairy or dietary calcium intake and
      measures of bone health. In the remaining 9 reports, the effects on bone health
      are small and 3 were confounded by vitamin D intake from milk fortified with
      vitamin D. Therefore, in clinical, longitudinal, retrospective, and cross
      sectional studies, neither increased consumption of dairy products, specifically,
      nor total dietary calcium consumption has shown even a modestly consistent
      benefit for child or young adult bone health. CONCLUSION: Scant evidence supports
      nutrition guidelines focused specifically on increasing milk or other dairy
      product intake for promoting child and adolescent bone mineralization.

PMID- 15741381
TI  - Evaluation and management of pain in patients with Klippel-Trenaunay syndrome: a
      review.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare disorder that consists of a triad of
      capillary vascular malformation, venous malformations and/or varicose veins, and
      soft tissue and/or bony hypertrophy. Pain is a real and debilitating problem in
      these patients. We have observed 9 common causes of pain in KTS: (1) chronic
      venous insufficiency, (2) cellulitis, (3) superficial thrombophlebitis, (4) deep
      vein thrombosis, (5) calcification of vascular malformations, (6) growing pains,
      (7) intraosseous vascular malformation, (8) arthritis, and (9) neuropathic pain.
      The management of pain in patients with KTS depends on its cause. These patients
      are best evaluated initially in a center with an experienced multidisciplinary
      team that includes a primary health care provider, surgeons, and ancillary staff.
      The ongoing care of a patient with KTS often depends on a local provider who is
      more readily accessible to the patient but may not have the expertise of a large
      center to manage the complications of KTS. The purpose of this communication is
      to review the common causes of pain in these patients to provide local health
      care providers and patients and their families with appropriate management
      strategies.

PMID- 15741382
TI  - State-of-the-art interventions for office-based parental tobacco control.
AB  - Parental tobacco use is a serious health issue for all family members. Child
      health care clinicians are in a unique and important position to address parental
      smoking because of the regular, multiple contacts with parents and the harmful
      health consequences to their patients. This article synthesizes the current
      evidence-based interventions for treatment of adults and applies them to the
      problem of addressing parental smoking in the context of the child health care
      setting. Brief interventions are effective, and complementary strategies such as
      quitlines will improve the chances of parental smoking cessation. Adopting the 5
      A's framework strategy (ask, advise, assess, assist, and arrange) gives each
      parent the maximum chance of quitting. Within this framework, specific
      recommendations are made for child health care settings and clinicians. Ongoing
      research will help determine how best to implement parental smoking-cessation
      strategies more widely in a variety of child health care settings.

PMID- 15741383
TI  - Scientifically unsupported and supported interventions for childhood
      psychopathology: a summary.
AB  - Although numerous scientifically supported treatments are available for childhood
      psychiatric disorders, many of the most popular interventions for these
      conditions are based on weak or nonexistent data. This article offers basic
      guidelines for distinguishing scientifically supported from unsupported
      treatments for 3 important childhood psychiatric disorders: autistic disorder,
      attention-deficit/hyperactivity disorder, and conduct disorder. A key challenge
      for the future will be to place the treatment of childhood psychiatric disorders
      on firmer scientific footing.

PMID- 15741384
TI  - Training young pediatricians as leaders for the 21st century.
AB  - OBJECTIVE: To conduct a needs assessment with young pediatricians who participate
      in a leadership training program and to evaluate the effectiveness of that
      program. METHODS: In concert with the Johnson & Johnson Pediatric Institute, LLC,
      the American Academy of Pediatrics developed a 1-year strategy to train
      pediatricians who are <40 years old or <5 years in practice in leadership skills.
      Participants were nominated by American Academy of Pediatrics chapters and/or
      sections and were required to complete a detailed needs assessment, attend a 3
      day training program, and commit to 1 leadership-related behavior change to be
      implemented within 6 months. A preanalytic/postanalytic design strategy was used.
      RESULTS: A total of 56 applicants representing 33 US states participated; 44.6%
      were male, and more than half (51.8%) were employed at a medical school/hospital.
      The needs assessment indicated that participants were confident in many of their
      leadership qualities but desired increased training, particularly in areas of
      time and priority management and leading "from the middle." Postsurvey
      instruments (n = 54, 96% response rate) determined that participants positively
      evaluated the training program and improved in self-reported basic competencies;
      87% also reported fully or partially achieving a leadership-related goal
      identified in a behavior change contract. CONCLUSIONS: Results demonstrate that
      young physicians are eager for leadership training and that continuing medical
      education in this area can be provided with positive results. Core competencies,
      curriculum, and evaluative tools need to be developed further and training
      opportunities need to be expanded to other subpopulations of pediatricians and
      pediatric health care providers.

PMID- 15741385
TI  - Complementary therapies in pediatrics: a legal perspective.
AB  - Increasing use of complementary and alternative medicine (CAM) therapies such as
      chiropractic, massage therapy, and herbal medicine, raises questions about the
      clinically appropriate use of CAM in pediatrics. Nonjudicious use of CAM
      therapies may cause either direct harm or, by creating an unwarranted financial
      and emotional burden, indirect harm. When advising patients concerning CAM
      therapies, pediatricians face 2 major legal risks: medical malpractice and
      professional discipline. Pediatricians can incorporate these considerations into
      advising and clinical decision-making about CAM therapies to address the best
      interest of the pediatric patient while helping to manage potential liability
      risk. This article provides a suggested framework, including asking the following
      questions: (1) Do parents elect to abandon effective care when the child's
      condition is serious or life-threatening? (2) Will use of the CAM therapy
      otherwise divert the child from imminently necessary conventional treatment? (3)
      Are the CAM therapies selected known to be unsafe and/or ineffective? (4) Have
      the proper parties consented to the use of the CAM therapy? (5) Is the risk
      benefit ratio of the proposed CAM therapy acceptable to a reasonable, similarly
      situated clinician, and does the therapy have at least minority acceptance or
      support in the medical literature? Such an approach ideally can help guide the
      pediatrician toward clinical conduct that is clinically responsible, ethically
      appropriate, and legally defensible.

PMID- 15741386
TI  - Bone health: it's more than calcium intake.

PMID- 15741387
TI  - Therapy is more than treatment.

PMID- 15741388
TI  - Corticosteroids and chronic lung disease: time for another randomized, controlled
      trial?

PMID- 15741389
TI  - Challenges in the diagnosis and management of neonatal herpes simplex virus
      encephalitis.

PMID- 15741390
TI  - Are the 21-year-old Baby Doe rules misunderstood or mistaken?

PMID- 15741391
TI  - Melanoma in children: heightened awareness of an uncommon but often curable
      malignancy.

PMID- 15741392
TI  - Herpes simplex virus encephalitis during suppressive therapy with acyclovir in a
      premature infant.
AB  - Cutaneous herpes simplex virus type 2 (HSV-2) infection was recognized at 19 days
      of age in a 1415-g female infant born at 31 weeks of gestation. Cerebrospinal
      fluid (CSF) HSV polymerase chain reaction (PCR) was negative, and MRI of the
      brain was normal. After a 14-day course of high-dose intravenous acyclovir, the
      infant developed a cutaneous recurrence at 38 days of age. CSF HSV PCR again was
      negative. She was subsequently begun on oral acyclovir to prevent cutaneous
      reactivation of HSV. At 3 months of age, the infant developed HSV encephalitis as
      manifested by fever, seizures, abnormal CSF indices, abnormal brain MRI, and
      positive CSF HSV PCR. No cutaneous disease was present. It is not known whether
      the HSV encephalitis in our patient represented reactivation of previously
      unrecognized central nervous system infection or new onset of central nervous
      system disease as a result of spread from other tissue or site to the brain. The
      failure of oral acyclovir to prevent such an occurrence, however, highlights gaps
      in our understanding of the pathogenesis of neonatal HSV disease and questions
      the use of acyclovir suppression to prevent neurologic sequelae.

PMID- 15741393
TI  - Eyelid mass as the presenting finding in a child with Down syndrome and acute
      megakaryoblastic leukemia.
AB  - Children with Down syndrome are at increased risk of developing acute
      megakaryoblastic leukemia (AML). Therefore, physicians caring for children with
      Down syndrome should be familiar with the presenting features of AML. We describe
      a child with Down syndrome presenting with a left eyelid mass 1 month before a
      diagnosis of acute AML.

PMID- 15741394
TI  - Chronic abdominal pain in children.
AB  - Children and adolescents with chronic abdominal pain pose unique challenges to
      their caregivers. Affected children and their families experience distress and
      anxiety that can interfere with their ability to perform regular daily
      activities. Although chronic abdominal pain in children is usually attributable
      to a functional disorder rather than organic disease, numerous misconceptions,
      insufficient knowledge among health care professionals, and inadequate
      application of knowledge may contribute to a lack of effective management. This
      clinical report accompanies a technical report (see page e370 in this issue) on
      childhood chronic abdominal pain and provides guidance for the clinician in the
      evaluation and treatment of children with chronic abdominal pain. The
      recommendations are based on the evidence reviewed in the technical report and on
      consensus achieved among subcommittee members.

PMID- 15741395
TI  - Tobacco, alcohol, and other drugs: the role of the pediatrician in prevention,
      identification, and management of substance abuse.
AB  - Substance abuse remains a major public health concern, and pediatricians are
      uniquely positioned to assist their patients and families with its prevention,
      detection, and treatment. The American Academy of Pediatrics has highlighted the
      importance of such issues in a variety of ways, including its guidelines for
      preventive services. The harmful consequences of tobacco, alcohol, and other drug
      use are a concern of medical professionals who care for infants, children,
      adolescents, and young adults. Thus, pediatricians should include discussion of
      substance abuse as a part of routine health care, starting with the prenatal
      visit, and as part of ongoing anticipatory guidance. Knowledge of the nature and
      extent of the consequences of tobacco, alcohol, and other drug use as well as the
      physical, psychological, and social consequences is essential for pediatricians.
      Pediatricians should incorporate substance-abuse prevention into daily practice,
      acquire the skills necessary to identify young people at risk of substance abuse,
      and provide or facilitate assessment, intervention, and treatment as necessary.

PMID- 15741396
TI  - Adolescent bariatric surgery: treatment delayed may be treatment denied.

PMID- 15741397
TI  - National standard for Death-Scene Investigation of Sudden, Unexpected Infant
      Deaths in the United States.

PMID- 15741399
TI  - Hyperbilirubinemia guidelines in newborn infants.

PMID- 15741400
TI  - Blood pressure tables.

PMID- 15741404
TI  - Waiver of prospective consent for pediatric resuscitation research.

PMID- 15741401
TI  - Extended-interval aminoglycosides in children: more guidance is needed.

PMID- 15741406
TI  - Prevention of kernicterus: a lesson from the past.

PMID- 15741408
TI  - Physiologically redefining bronchopulmonary dysplasia.

PMID- 15741409
TI  - Rethinking the rethinking about "well-child" care.

PMID- 15741411
TI  - Seasonal allergic rhinitis study results of questionable relevance to homeopathy.

PMID- 15741412
TI  - Interventions to improve treatment of respiratory infections in ambulatory
      managed-care patients.
AB  - OBJECTIVE: To review the literature on managed-care initiatives to improve
      antimicrobial use in respiratory tract infections (RTIs) and examine whether
      efforts were successful in decreasing antibiotic prescribing when an antibiotic
      was not indicated or in increasing the frequency with which a preferred
      antimicrobial agent was chosen when an antibiotic was appropriate. DATA SOURCES:
      A computerized search of Ovid MEDLINE was conducted for research articles
      published between 1966 and September 2004 using a key word search of MeSH subject
      headings and titles. Search terms included managed care or health maintenance
      organization and antibacterial agents or antibiotic or antimicrobial. STUDY
      SELECTION AND DATA EXTRACTION: Studies evaluating initiatives in ambulatory
      managed-care environments and the effects of managed care on treatment of RTIs
      were chosen. Articles addressing both population and individual level tools were
      included. DATA SYNTHESIS: Initiatives have been attempted in a variety of managed
      care models. In some studies, multidimensional educational interventions were
      effective in decreasing antimicrobial prescribing rates for RTIs. However, in
      other studies, no decrease in antimicrobial prescribing after implementation of
      an evidence-based guideline or initiation of an educational intervention was
      observed. In one successful study, patient satisfaction was similar between
      groups. Each study had limitations in design or generalizability. Several studies
      had strengths, including using randomized groups or offering multidimensional
      educational efforts. CONCLUSIONS: Randomized prospective studies of interventions
      to improve antimicrobial prescribing for RTIs in managed care have been variably
      successful. Because the topic is one of ongoing importance, it will continue to
      be an area of research.

PMID- 15741413
TI  - High-dose zolpidem dependence in a patient with chronic facial pain.

PMID- 15741414
TI  - Drug holiday in Huntington's disease.

PMID- 15741415
TI  - Including the assessment of nontraditional factors in pharmacy school admissions.
AB  - OBJECTIVE: To review the relevant literature regarding the predictive ability of
      cognitive measures (ie, Pharmacy College Admissions Test [PCAT] scores and
      prepharmacy grade point average [GPA]) on both academic and clinical performance
      and discuss the inclusion of nontraditional assessment during the admissions
      process. DATA SOURCES: Articles were identified through searches of International
      Pharmaceutical Abstracts (1970-April 2004), MEDLINE (1966-January 2004), and ERIC
      (1966-April 2004) using the key words admissions variables, predictors of
      success, Pharmacy College Admissions Test, grade point average, cognitive
      variables, and noncognitive variables. STUDY SELECTION AND DATA EXTRACTION: Cross
      sectional, longitudinal, and retrospective studies, as well as reviews, regarding
      pharmacy school and other higher education admissions' variables were included in
      this review. DATA SYNTHESIS: Many pharmacy school admissions committees give a
      majority weight to the traditional cognitive markers of prepharmacy GPA and PCAT
      scores when selecting viable applicants. Doing so may be problematic due to the
      magnitude of the relationship between traditional cognitive predictors and
      pharmacy school performance. CONCLUSIONS: Based on this review, a cogent argument
      is advanced for the need to examine, in addition to PCAT scores and GPAs, such
      nontraditional factors as empathy, citizenship, and ethical behavior. This may
      increase the predictive ability of preadmission factors on pharmacy school
      didactic and clinical performance. Schools of pharmacy can do this through
      questionnaires and interviews designed to assess nontraditional variables.

PMID- 15741416
TI  - When does pharmaceutical care impact health outcomes? A comparison of community
      pharmacy-based studies of pharmaceutical care for patients with asthma.
AB  - BACKGROUND: Pharmaceutical care (PC) as a philosophy of care and practice model
      is now >14 years old. It is important to determine whether PC influences health
      outcomes. Such outcomes are best studied in specific disease states where
      variables are minimized and specific outcomes have been established. We analyzed
      4 multi-site controlled studies that evaluated PC in community pharmacies for
      patients with asthma. Study results varied widely. OBJECTIVE: To understand
      factors contributing to positive outcomes from PC for asthma. METHODS: The 4
      studies were compared on the basis of 10 aspects of their research design, as
      well as 10 elements of PC. Dr. McLean conducted the initial analysis, and his
      assessments were confirmed by Dr. MacKeigan. RESULTS: Important differences were
      found in the type of pharmacy where PC was delivered (chain vs independent), how
      pharmacies were selected (required vs volunteered), patient selection (on asthma
      medication vs uncontrolled disease), pharmacist training (4-h workshop vs
      certification over several weeks), the nature of PC protocol (computer reminders
      vs detailed care protocol), rigor of the protocol (intervention vs requirement to
      reach self-management), and the level of pharmacist adherence to the PC protocol
      (<50% vs 90%). Differences were also found in study design. CONCLUSIONS: More
      favorable PC outcomes were associated with use of all elements of PC, independent
      pharmacies, pharmacist certification, a detailed PC protocol, targeting patients
      with uncontrolled asthma, and a practice system facilitating PC.

PMID- 15741417
TI  - Herbal use among US elderly: 2002 National Health Interview Survey.
AB  - BACKGROUND: Use of herbal products among the elderly is an important concern for
      healthcare professionals. The presence of polypharmacy and multiple comorbidities
      places the elderly at high risk for herb-drug and herb-disease interactions.
      Limited data exist regarding herbal use among the US elderly population.
      OBJECTIVE: To evaluate the incidence of and attitudes toward herbal use in a
      nationally representative sample of US elderly patients >/=65 years of age.
      METHODS: We performed a descriptive analysis of public domain data collected in
      the 2002 National Health Interview Survey. Statistical analyses were conducted
      through use of SUDAAN software with Taylor series linearization for variance
      estimation. RESULTS: Analysis of weighted data revealed that 12.9% +/- 0.5% (mean
      +/- SE) of US elderly people had used an herbal supplement within the past 12
      months. Use was greatest among individuals 65-69 years of age, females, Hispanic
      and non-Hispanic ethnic minorities, and respondents with a greater income, higher
      education level, or more positive self-reported health status. Among elderly
      people purchasing over-the-counter and prescription drugs, herbal use was 13.9%
      +/- 0.6% and 12.8% +/- 0.6%, respectively. Glucosamine, echinacea, and garlic
      supplements represented the most common herbals used. Benefit from combined
      herbal and conventional therapy was the most common reason cited for use;
      however, 50.9% +/- 2.2% of users did not discuss herbal therapy with a medical
      professional. Several theoretical herb-disease interactions were identified.
      CONCLUSIONS: The use of herbal products among the US elderly has risen over the
      past 5 years, whereas discussion of such use with medical professionals remains
      suboptimal.

PMID- 15741418
TI  - Leflunomide and azathioprine combination in refractory adult-onset Still's
      disease.
AB  - OBJECTIVE: To present a case of Adult-onset Still's disease (ASD) in a patient
      who was successfully treated with leflunomide and azathioprine. CASE SUMMARY: A
      24-year-old woman with ASD was initially treated with indomethacin,
      corticosteroids, and hydroxychloroquine; there was no clinical improvement.
      Methotrexate was added to the regimen, followed by azathioprine. The patient
      still experienced disease flares with this treatment, and cyclophosphamide was
      started. However, because of persisting disease activity, leflunomide combined
      with azathioprine was given. Only on this regimen was complete disease control
      achieved, with a normal erythrocyte sedimentation rate as well as normal C
      reactive protein and ferritin levels. No recurrences or adverse effects
      attributable to leflunomide or azathioprine were observed at the one-year follow
      up. DISCUSSION: Clinical experience concerning leflunomide and azathioprine
      combination in ASD is limited. This combination may be modifying the clinical
      expression of ASD through its effects on T lymphocyte clonal expansion and
      production of proinflammatory cytokines. CONCLUSIONS: Leflunomide combined with
      azathioprine appears to be an effective and safe treatment of ASD.

PMID- 15741419
TI  - Medication use patterns after gastric bypass surgery for weight management.
AB  - BACKGROUND: Bariatric surgery, commonly gastric bypass, is an effective
      intervention in achieving sustained weight loss in patients with a body mass
      index (BMI) >40 kg/m(2). Currently, there are few data in the literature
      describing medication use after bariatric surgery. OBJECTIVE: To document the
      change in medication use patterns over a 2-year period in patients who had
      gastric bypass surgery. METHODS: Institutional review board approval was obtained
      for this ongoing, prospective longitudinal study. Adults (>18 y) scheduled for
      gastric bypass surgery were recruited. Clinical and demographic data, including
      age, gender, weight, height, BMI, number of obesity-related comorbidities, and
      number of medications and nutritional supplements, were obtained by medical chart
      review. RESULTS: One hundred fourteen patients (87 females) were recruited. The
      mean +/- SD age was 45 +/- 9 years. Patients had multiple obesity-related
      comorbid diseases for which they were receiving medication. Drug therapy for
      diabetes and hypertension was significantly reduced (p < 0.05). All patients were
      required to take additional nutritional supplements and medications associated
      with surgery postoperatively. CONCLUSIONS: Bariatric surgery has a positive
      benefit in terms of reduction intake of medication associated with obesity
      related comorbid disease. However, there is limited reduction in the overall
      number of drugs and supplements being consumed by the patient, especially during
      the first year postoperatively.

PMID- 15741420
TI  - Treatment of seasonal allergic rhinitis using homeopathic preparation of common
      allergens in the southwest region of the US: a randomized, controlled clinical
      trial.
AB  - BACKGROUND: Studies using homeopathy have reported beneficial effects from
      treating allergy-related conditions. OBJECTIVE: To investigate the effects of a
      homeopathic drug prepared from common allergens (tree, grass, weed species)
      specific to the Southwest region of the US. METHODS: A 4-week, double-blind
      clinical trial comparing homeopathic preparations with placebo was conducted in
      the Phoenix metropolitan area during the regional allergy season from February to
      May. Participants included 40 men and women, 26-63 years of age, diagnosed with
      moderate to severe seasonal allergic rhinitis symptoms. Study outcomes included
      allergy-specific symptoms using the rhinoconjunctivitis quality-of-life
      questionnaire (RQLQ), functional quality of life using the Medical Outcomes Study
      Short Form-36 (MOS SF-36), and the work productivity and activity impairment
      (WPAI) questionnaire. RESULTS: Scales from the RQLQ, MOS SF-36, and WPAI
      questionnaire showed significant positive changes from baseline to 4 weeks in the
      homeopathic group compared with the placebo group (p < 0.05). Subjects reported
      no adverse effects during the intervention period. CONCLUSIONS: These preliminary
      findings indicate potential benefits of the homeopathic intervention in reducing
      symptoms and improving quality of life in patients with seasonal allergic
      rhinitis in the Southwestern US.

PMID- 15741421
TI  - Cost-effectiveness of fluvastatin following successful first percutaneous
      coronary intervention.
AB  - BACKGROUND: In the LIPS (Lescol Intervention Prevention Study), fluvastatin 80
      mg/day reduced the risk of major adverse cardiac events (MACE) by 22% versus
      placebo (p = 0.01) following successful first percutaneous coronary intervention
      (PCI) in patients with stable or unstable angina or silent ischemia. The cost
      effectiveness of such therapy is unknown. OBJECTIVE: To evaluate the cost
      effectiveness of fluvastatin following successful first PCI from a US healthcare
      system perspective. METHODS: We used a Markov model to estimate expected outcomes
      and costs of 2 alternative treatment strategies following successful first PCI in
      patients with stable or unstable angina or silent ischemia: (1) diet/lifestyle
      counseling plus immediate fluvastatin 80 mg/day; and (2) diet/lifestyle
      counseling only, with initiation of fluvastatin 80 mg/day following occurrence of
      future nonfatal MACE. The model was estimated with data from LIPS and other
      published sources. Cost-effectiveness was calculated as the ratio of the
      difference in expected medical-care costs to the expected difference in life
      years (LYs) and quality-adjusted life-years (QALYs) alternatively. RESULTS:
      Treatment with fluvastatin following successful first PCI was found to increase
      life expectancy by 0.78 years (QALYs 0.68). Cost-effectiveness of fluvastatin
      following successful first PCI is 13 505 dollars per LY (15 454 dollar per QALY)
      saved. Ratios are lower for patients with diabetes (9396 dollar per LY; 10 718
      dollar per QALY) and those with multivessel disease (9662 dollar per LY; 11 076
      dollar per QALY). Findings were robust with respect to changes in key model
      parameters and assumptions. CONCLUSIONS: Fluvastatin therapy following PCI is
      cost-effective compared with other generally accepted medical interventions.

PMID- 15741422
TI  - Use of a modified dosing weight for heparin therapy in a morbidly obese patient.
AB  - OBJECTIVE: To report a case of successful anticoagulation using a modified dosing
      weight (DW) for unfractionated heparin (UFH) therapy in a morbidly obese female.
      CASE SUMMARY: A 54-year-old morbidly obese (182.4 kg, 155 cm) white female
      presented to the emergency department with tachycardia, shortness of breath, and
      chest pain, and was diagnosed with a pulmonary embolism. Anticoagulation with UFH
      was initiated. A modified DW of 120 kg was obtained from the average of the
      actual body weight (ABW) and ideal body weight ( approximately 50 kg). We
      selected this modified DW to account for heparin's altered volume of distribution
      in an obese patient and avoid potentially supratherapeutic activated partial
      thromboplastin times (aPTTs) using ABW and subtherapeutic aPTTs using DW. Therapy
      was initiated with a bolus dose of 9600 units (80 units/kg x 120 kg) and
      continuous infusion rate of 2160 units/h (18 units/kg/h x 120 kg). This infusion
      rate was maintained throughout the course of heparin therapy and was successful
      in maintaining therapeutic aPTTs. DISCUSSION: Proper diagnosis and rapid
      initiation of therapy prevent mortality in patients with PE. Although weight
      based heparin nomograms provide standardization through initial bolus and
      continuous infusion recommendations, many do not address dosing in morbidly obese
      patients. Several retrospective studies have evaluated actual, dosing, and ideal
      body weights for heparin therapy in obese patients; however, none has evaluated
      modified DW. In our patient, successful anticoagulation was objectively
      confirmed. CONCLUSIONS: Further investigation is necessary to determine the
      optimal DW for UFH in morbidly obese patients presenting with acute thrombosis.

PMID- 15741424
TI  - Can 1 microg of cosyntropin be used to evaluate adrenal insufficiency in
      critically ill patients?
AB  - OBJECTIVE: To evaluate the utility of cosyntropin 1 microg in assessing adrenal
      function in critically ill patients. DATA SOURCES: A computerized literature
      search using MEDLINE, EMBASE, International Pharmaceutical Abstracts, and the
      Cochrane Database (1966-August 2004) was undertaken for trials evaluating
      cosyntropin 1 mug using the following search terms: adrenocorticotropin-releasing
      hormone (ACTH), cosyntropin, adrenal insufficiency, cortisol, corticosteroids,
      glucocorticoids, sepsis, septic shock, diagnosis, critically ill, intensive care,
      and critical care. STUDY SELECTION AND DATA SYNTHESIS: Identifying patients with
      sepsis with relative adrenal insufficiency (AI) using cosyntropin testing may
      identify those likely to benefit from corticosteroids. The results of 5
      heterogeneous studies in non-intensive care unit (ICU) patients suggest that both
      1 microg and 250 microg of cosyntropin stimulate similar cortisol responses and
      that testing using both doses correlates well with results from insulin tolerance
      testing. Some data from non-ICU patients suggest that the 1-microg test may be
      more sensitive to detect AI; 3 heterogeneous studies in ICU patients confirmed
      the improved sensitivity of the 1-microg test. CONCLUSIONS: Use of cosyntropin 1
      microg should detect AI in all patients who would have been diagnosed using 250
      microg. Unfortunately, all of the clinical trials evaluating the role of
      corticosteroids in septic shock that used the cosyntropin stimulation test
      administered 250 microg. Extrapolation of the existing guidelines to treat
      patients with septic shock testing positive for relative AI using the 1-microg
      test may provide effective therapy to appropriate patients not diagnosed by the
      250-microg testing or may introduce additional adverse effects in patients who
      should not receive corticosteroids. Large-scale, head-to-head comparison data of
      steroid effectiveness after 1- and 250-microg ACTH stimulation tests are needed
      to expand upon these promising results.

PMID- 15741423
TI  - Hyponatremia with consciousness disturbance associated with esomeprazole.

PMID- 15741425
TI  - Effects of natural health products on blood pressure.
AB  - OBJECTIVE: To review the scientific literature to identify reports of the effects
      of natural health products (NHPs) on blood pressure. DATA SOURCES: Electronic
      databases (MEDLINE [1965-May 2004] via PubMed, the Cochrane Library [1995-May
      2004], International Pharmaceutical Abstracts [1970-May 2004], Iowa Drug
      Information Services [1965-May 2004]) were searched using the key words medicine,
      herbal plants, medicinal plant preparations, phytotherapy,
      angiosperms/therapeutic use, gymnosperms/therapeutic use, ethnopharmacology,
      pharmacognosy, blood pressure, hypertension, hypotension, and diuretic. Searches
      were not limited by date, language, or publication type. Review articles and
      texts, as well as reference lists of relevant articles, were used to identify
      additional reports. STUDY SELECTION AND DATA EXTRACTION: Articles (English
      language after 1980) were assigned to the following categories: human study, case
      report, animal study, in vitro study, or theoretical prediction based on chemical
      constituents. Discussions of mechanisms of action were noted. DATA SYNTHESIS: A
      comprehensive search of the scientific literature identified NHPs capable of
      affecting blood pressure. Case reports and clearly defined mechanisms of action
      provided strong evidence for the ability of ephedra and licorice to increase
      blood pressure. Coenzyme Q(10) was reported to decrease systolic and diastolic
      blood pressure, although the mechanism is unclear. The clinical significance of
      the blood pressure effects of other NHPs is unclear due to lack of conclusive in
      vivo data, as well as substantial variability in the chemical content of
      preparations of NHPs. CONCLUSIONS: Among published information, there is little
      definitive evidence with regard to the impact of NHPs on blood pressure.
      Additionally, effects may vary in a given patient with the formulation and
      standardization of a particular product. Until research better characterizes the
      effect of NHPs on blood pressure, patients should be encouraged to talk with
      their healthcare provider before starting or stopping any herbal product.

PMID- 15741426
TI  - Esomeprazole-induced central fever with severe myalgia.
AB  - OBJECTIVE: To report a case of central fever associated with severe myalgia
      following esomeprazole. CASE SUMMARY: A 64-year-old man presented with intense
      cephalalgia; severe, diffuse myalgia; and fever (>40 degrees C) after
      esomeprazole initiation for treatment of gastritis. Five hours after ingestion of
      the first esomeprazole pill (40 mg), the patient developed fever associated with
      cephalalgia and myalgia. This condition lasted about 40 hours and disappeared
      spontaneously. Symptoms partially responded to acetaminophen. Four days later,
      the patient received a second dose of esomeprazole 40 mg. Subsequently, 4 hours
      later, fever (>40 degrees C), headache, and difficulty in the movement of all
      parts of the body recurred. Neurologic examination was negative except for a
      minor state of disorientation. All reflexes were normal or slightly decreased. No
      skin lesions or breathing difficulty was noted. Routine blood tests were normal.
      Again, symptoms resolved spontaneously about 40 hours later. DISCUSSION: The
      temporal connection between esomeprazole intake and the onset of fever suggests a
      probable causal link, as confirmed by the Naranjo probability scale. However, the
      pathogenic mechanism remains unclear. Considering that esomeprazole is able to
      cross the blood-brain barrier, its peak serum concentration is reached 90-180
      minutes after oral administration, and its serum half-life is approximately 2
      hours, we assume that the appearance of fever with accompanying neurologic and
      muscular symptoms might result from the drug interference with the hypothalamic
      regulatory center of body temperature. CONCLUSIONS: Hyperpyrexia of central
      origin associated with intense cephalalgia and myalgia may occur as an adverse
      effect of esomeprazole therapy.

PMID- 15741427
TI  - Streamlining weaning: protocols and weaning units.

PMID- 15741428
TI  - Consultations for asthma: will greater patient involvement deliver better health?

PMID- 15741429
TI  - The exhaled biomarker puzzle: bacteria play their card in the exhaled nitric
      oxide-exhaled breath condensate nitrite game.

PMID- 15741431
TI  - Muscling into cystic fibrosis airways.

PMID- 15741430
TI  - Brave new world for interventional bronchoscopy.

PMID- 15741432
TI  - Breathing new life into respiratory medicine? Report of the 2004 BTS Winter
      Meeting.

PMID- 15741433
TI  - Outcomes, cost and long term survival of patients referred to a regional weaning
      centre.
AB  - BACKGROUND: Regional weaning centres provide cost effective care for patients who
      have undergone prolonged mechanical ventilation. There are few published European
      data on outcomes in these patients. METHODS: Patients admitted for weaning to the
      Lane Fox Respiratory Unit (LFU) between January 1997 and December 2000 were
      identified. The proportion weaned from mechanical ventilation, in-hospital
      mortality, and subsequent survival after discharge were examined. RESULTS: A
      total of 153 patients had been ventilated for a median of 26 days before
      transfer. The daily cost per patient stay was 1350. Fifty eight patients (38%)
      were fully weaned, 42 (27%) died, and 53 (35%) required ventilatory support at
      discharge from hospital of whom 36 (24%) required only nocturnal ventilation.
      Univariate analysis showed increasing age (OR 1.06, p<0.001), length of ICU stay
      (OR 1.02, p = 0.001), APACHE II predicted risk of death score (OR 1.02, p =
      0.05), and a surgical cause for admission (OR 4.04) were associated with
      mortality. Neuromuscular/chest wall conditions were associated with low mortality
      (OR 0.36) but low likelihood of weaning from ventilation (OR 0.28). Female sex
      (OR 2.13, p = 0.03) and COPD (OR 2.81) were associated with successful weaning.
      Overall survival at 3 years from admission was 47%. Long term survival was lowest
      in patients with COPD. CONCLUSIONS: Most patients survived to leave hospital, the
      majority having been liberated from ventilatory support. Survivors were younger
      and spent less time ventilated in the referring ICU. The underlying diagnosis
      determined success of weaning, hospital survival, and long term outcome.

PMID- 15741434
TI  - Sputum eosinophilia and the short term response to inhaled mometasone in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: An association between the sputum eosinophil count and the response
      to a 2 week course of prednisolone has previously been reported in patients with
      chronic obstructive pulmonary disease (COPD). Whether the response to inhaled
      corticosteroids is related to the presence of eosinophilic inflammation is
      unclear. METHODS: A randomised, double blind, crossover trial of placebo and
      mometasone furoate (800 microg/day), each given for 6 weeks with a 4 week washout
      period, was performed in subjects with COPD treated with bronchodilator therapy
      only. Spirometric tests, symptom scores, chronic respiratory disease
      questionnaire (CRQ), and induced sputum were performed before and after each
      treatment phase. RESULTS: Ninety five patients were recruited of which 60 were
      randomised. Overall there were no treatment associated changes in forced
      expiratory volume in 1 second (FEV(1)), total CRQ, or sputum characteristics.
      After stratification into tertiles by baseline eosinophil count, the net
      improvement in post-bronchodilator FEV(1) increased with mometasone compared with
      placebo progressively from the least to the most eosinophilic tertile. The mean
      change in post-bronchodilator FEV(1) with mometasone compared with placebo in the
      highest tertile was 0.11 l (95% CI 0.03 to 0.19). This improvement was not
      associated with a fall in the sputum eosinophil count. CONCLUSIONS: An increased
      sputum eosinophil count is related to an improvement in post-bronchodilator
      FEV(1) following treatment with inhaled mometasone in COPD, but the improvement
      is not associated with a reduction in the sputum eosinophil count.

PMID- 15741435
TI  - Involvement in treatment decisions: what do adults with asthma want and what do
      they get? Results of a cross sectional survey.
AB  - BACKGROUND: Current healthcare policy advocates patient participation in
      treatment decision making. However, in asthma there is little evidence regarding
      patients' views on such involvement. This study explored the preferred and
      perceived level of involvement in treatment decisions, rationales for role
      preference, perceived facilitators of/barriers to involvement, and the
      interrelationship of role preference and demographic variables in a sample of
      patients with asthma. METHODS: A cross sectional survey was performed of 230
      adults with clinician diagnosed asthma from 10 primary care sites and one
      specialist respiratory centre in north-west England. Preferred role in treatment
      decisions was assessed using the Control Preferences Scale. RESULTS: Fifty five
      (23.9%) preferred an active role, 82 (35.7%) a collaborative role, and 93 (40.4%)
      a passive role; 19 (8.2%) perceived their role as active compared with 45 (19.6%)
      collaborative and 166 (72.2%) passive. Only 33.5% (n = 77) of respondents
      attained their most preferred role; 55.2% (n = 127) were less involved than they
      preferred. Patient related, professional related, and organisational factors,
      especially quality and duration of consultations, facilitated or hampered
      involvement. Role preferences were not strongly associated with demographic
      variables or asthma severity. CONCLUSIONS: This study in patients with asthma
      highlights the fact that there is a need for professional and patient education
      regarding partnership working, skilful communication, and innovative approaches
      to service delivery.

PMID- 15741436
TI  - Asthma in children with sickle cell disease and its association with acute chest
      syndrome.
AB  - BACKGROUND: Pulmonary complications are a major cause of morbidity and mortality
      in sickle cell disease (SCD). The relationship of asthma with SCD and acute chest
      syndrome (ACS) remains uncertain. A study was undertaken to test the hypotheses
      that asthma and bronchial hyperreactivity (BHR) are more common in children with
      SCD than in ethnic matched controls and that SCD children with atopic asthma are
      more likely to have recurrent episodes of ACS. METHODS: A modified International
      Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was administered
      and skin prick tests undertaken in 80 children with SCD and 80 ethnic matched
      controls aged 5-10 years. BHR was assessed by measurement of forced expiratory
      volume in 1 second before and after a bronchodilator (albuterol 200 mug) or an
      exercise challenge. RESULTS: Asthma (48% v 22%, p = 0.002) and BHR (p = 0.02) but
      not atopy were more common in children with SCD than in controls. Atopy (66.6% v
      29%, p = 0.007) and asthma (80% v 40%, p = 0.005), particularly atopic asthma
      (53% v 12%, p<0.001), were more common in children with SCD who had suffered
      recurrent episodes of ACS than in those who had suffered a single or no episode.
      CONCLUSIONS: Asthma and BHR are more common in children with SCD than in ethnic
      matched controls, and atopic asthma appears to be associated with recurrent ACS.
      Early and effective anti-asthma therapy might reduce the pulmonary morbidity
      associated with SCD.

PMID- 15741438
TI  - Exhaled nitric oxide predicts asthma relapse in children with clinical asthma
      remission.
AB  - BACKGROUND: Nitric oxide in exhaled air (FE(NO)) is a marker of eosinophilic
      airway inflammation. A study was undertaken to determine whether FE(NO) predicts
      asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids
      are discontinued. METHODS: Forty children (21 boys) of mean age 12.2 years on a
      median dose of 400 mug budesonide or equivalent (range 100-400) were included.
      FE(NO) was measured before and 2, 4, 12, and 24 weeks after withdrawal of
      steroids. A relapse was defined as more than one exacerbation per month, or need
      for beta agonist treatment on 4 days per week for at least 2 weeks, or diurnal
      peak flow variability of >20%. FE(NO) measurements were performed online with an
      expiratory flow of 50 ml/s. RESULTS: Nine patients relapsed. Two and 4 weeks
      after withdrawal of steroids geometric mean FE(NO) in children who were about to
      relapse was higher than in those who did not relapse: 35.3 ppb v 15.7 ppb at 2
      weeks (ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb v 15.9 ppb at 4 weeks
      (ratio 2.6; 95% CI 1.3 to 5.1). An FE(NO) value of 49 ppb at 4 weeks after
      discontinuation of steroids had the best combination of sensitivity (71%) and
      specificity (93%) for asthma relapse. CONCLUSION: FE(NO) 2 and 4 weeks after
      discontinuation of steroids in asymptomatic asthmatic children may be an
      objective predictor of asthma relapse.

PMID- 15741437
TI  - The CD14 C-159T polymorphism is not associated with asthma or asthma severity in
      an Australian adult population.
AB  - BACKGROUND: CD14 functions as a multifunctional receptor for bacterial cell wall
      components including endotoxin and lipopolysaccharide and is likely to play a
      role in the polarisation of T lymphocytes into Th1 and Th2 subsets, thereby
      influencing the cytokine profile and subsequent IgE production in response to
      antigen/allergen contact in allergic phenotypes. A functional C-159T polymorphism
      has been described in the promoter region of the gene and has been associated
      with increased gene expression, atopy, and non-atopic asthma in different ethnic
      populations. A study was undertaken to examine the association between the C-159T
      polymorphism and asthma, asthma severity, and atopy in a large Australian white
      population. METHODS: PCR-RFLP analysis was used to characterise the C-159T
      polymorphism in mild (n = 264), moderate (n = 225) and severe (n = 79) asthmatic
      patients and non-asthmatic controls (n = 443), including atopic (n = 688) and non
      atopic (n = 323) individuals. Association analyses were performed using chi(2)
      tests. RESULTS: There was no association between the polymorphism and asthma (p =
      0.468) or asthma severity (p = 0.727), and only a very weak association with
      atopy (p = 0.084). A meta-analysis of all studies conducted to date revealed
      similar genotypic frequencies in white ethnic populations and confirmed that
      there was no overall association with atopy (p = 0.52) or asthma (p = 0.23),
      although there was significant between study heterogeneity (p = 0.01).
      CONCLUSIONS: This study confirms that there is no association between the CD14 C
      159T polymorphism and asthma or asthma severity and a weak association between
      this polymorphism and atopy in an adult population.

PMID- 15741439
TI  - Origin of nitrite and nitrate in nasal and exhaled breath condensate and relation
      to nitric oxide formation.
AB  - BACKGROUND: Raised concentrations of nitrate and nitrite have been found in
      exhaled breath condensate (EBC) in airway disease, and it has been postulated
      that this reflects increased nitric oxide (NO) metabolism. However, the chemical
      and anatomical origin of nitrate and nitrite in the airways has not yet been
      sufficiently studied. METHODS: The fraction of exhaled NO at an exhalation flow
      rate of 50 ml/s (FE(NO)) and nitrite and nitrate in EBC, nasal condensate, and
      saliva were measured in 17 tracheostomised and 15 non-tracheostomised subjects,
      all of whom were non-smokers without respiratory disease. Tracheal and oral
      samples were taken from the tracheostomised subjects and nasal (during velum
      closure) and oral samples from the non-tracheostomised subjects. Measurements
      were performed before and after sodium nitrate ingestion (10 mg/kg) and use of
      antibacterial mouthwash (chlorhexidine 0.2%). RESULTS: In tracheostomised
      subjects oral FE(NO) increased by 90% (p<0.01) while tracheal FE(NO) was not
      affected 60 minutes after nitrate ingestion. Oral EBC nitrite levels were
      increased 23-fold at 60 minutes (p<0.001) whereas the nitrite levels in tracheal
      EBC showed only a minor increase (fourfold, p<0.05). Nitrate was increased the
      same amount in oral and tracheal EBC at 60 minutes (2.5-fold, p<0.05). In non
      tracheostomised subjects oral FE(NO) and EBC nitrite increased after nitrate
      ingestion and after chlorhexidine mouthwash they approached baseline levels again
      (p<0.001). Nasal NO, nitrate, and nitrite were not affected by nitrate intake or
      mouthwash. At baseline, mouthwash with deionised water did not affect nitrite in
      oral EBC or saliva, whereas significant reductions were seen after antibacterial
      mouthwash (p<0.05 and p<0.001, respectively). CONCLUSIONS: Besides the salivary
      glands, plasma nitrate is taken up by the lower airways but not the nasal
      airways. Nitrate levels in EBC are thus influenced by dietary intake. Nitrate is
      reduced to nitrite by bacterial activity which takes place primarily in the
      oropharyngeal tract of healthy subjects. Only oropharyngeal nitrite seems to
      contribute to exhaled NO in non-inflamed airways, and there is also a substantial
      contribution of nitrite from the oropharyngeal tract during standard collection
      of EBC.

PMID- 15741440
TI  - Structural changes to airway smooth muscle in cystic fibrosis.
AB  - BACKGROUND: Chronic airway obstruction is characteristic of cystic fibrosis (CF)
      but there are few studies of airway smooth muscle remodelling in CF. METHODS:
      Airway smooth muscle content and mean airway smooth muscle cell size were
      measured by applying design-based stereology to bronchoscopic biopsy specimens
      obtained from seven subjects with CF and 15 healthy controls. RESULTS: The smooth
      muscle content increased by 63% in subjects with CF (mean (SD) 0.173 (0.08) v
      0.106 (0.042) mm(3) smooth muscle/mm(3) submucosa, mean difference -0.067; 95% CI
      -0.12 to -0.013, p = 0.017) but there was no increase in mean cell size (2705
      (351) v 2654 (757) microm(3), mean difference -51; 95% CI -687 to 585, p = 0.87).
      CONCLUSIONS: These findings indicate hyperplasia of airway smooth muscle cells
      without hypertrophy and suggest that accumulation of airway smooth muscle cells
      may contribute to airway narrowing and bronchial hyperresponsiveness in CF.

PMID- 15741441
TI  - Ultrasound guided cytological aspiration of supraclavicular lymph nodes in
      patients with suspected lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of death from cancer in the UK.
      Pathological diagnosis traditionally requires invasive procedures such as
      bronchoscopy, mediastinoscopy, or image guided biopsy. Ultrasound of the neck
      with fine needle aspiration cytology (FNAC) of enlarged but impalpable
      supraclavicular nodes has been used in patients with suspected lung cancer who
      have N2 or N3 disease on staging computed tomography (CT). If positive, this
      technique helps to both stage the patient and provide a cytological diagnosis.
      METHODS: 101 patients were enrolled prospectively over a 1 year period. FNAC was
      performed on all supraclavicular nodes over 5 mm in size using the capillary
      aspiration technique. RESULTS: Sixty one of the 101 patients had enlarged
      supraclavicular nodes and underwent FNAC. The overall malignant yield was 45.5%
      of patients scanned and 75.4% of patients sampled. As a result of FNAC, 43
      patients (42.6%) avoided more invasive procedures. CONCLUSION: Ultrasound guided
      FNAC is a promising, relatively non-invasive technique for the staging and
      diagnosis of patients with lung cancer.

PMID- 15741442
TI  - Effect of lung cancer surgery on quality of life.
AB  - BACKGROUND: Health related quality of life (HRQOL) after surgery is important,
      although very limited data are available on the QOL after lung cancer surgery.
      METHODS: The effect of surgery on HRQOL was assessed in a prospective study of
      110 patients undergoing potentially curative lung cancer surgery at Papworth
      Hospital, 30% of whom had borderline lung function as judged by forced expiratory
      volume in 1 second. All patients completed the EORTC QLQ-C30 and LC13 lung cancer
      module before surgery and again at 1, 3 and 6 months postoperatively. RESULTS: On
      average, patients had high levels of functioning and low levels of symptoms.
      Global QOL had deteriorated significantly 1 month after surgery (p = 0.001) but
      had returned to preoperative levels by 3 months (p = 0.93). Symptoms had worsened
      significantly at 1 month after surgery but had returned to baseline levels by 6
      months. Low values on the preoperative HRQOL scales were not significantly
      associated with poor surgical outcome. However, patients with low preoperative
      HRQOL functioning scales and high preoperative symptom scores were more likely to
      have poor postoperative (6 months) QOL. The only lung function measurement to
      show a marginally statistically significant association with quality of life at 6
      months after surgery was percentage predicted carbon monoxide transfer factor
      (Tlco). CONCLUSION: Although surgery had short term negative effects on quality
      of life, by 6 months HRQOL had returned to preoperative values. Patients with low
      HRQOL functioning scales, high preoperative symptom scores, and preoperative
      percentage predicted Tlco may be associated with worse postoperative HRQOL.

PMID- 15741443
TI  - Inhaled fluticasone in bronchiectasis: a 12 month study.
AB  - BACKGROUND: The clinical efficacy of inhaled corticosteroid (ICS) treatment has
      not been evaluated in bronchiectasis, despite the presence of chronic airway
      inflammation. METHODS: After three consecutive weekly visits, 86 patients were
      randomised to receive either fluticasone 500 mug twice daily (n = 43, 23F, mean
      (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years)
      and reviewed regularly for 52 weeks in a double blind fashion. RESULTS: 35 and 38
      patients in the fluticasone and placebo groups completed the study. Significantly
      more patients on ICS than on placebo showed improvement in 24 hour sputum volume
      (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced
      expiratory volume in 1 second, forced vital capacity, or sputum purulence score.
      Significantly more patients with Pseudomonas aeruginosa infection receiving
      fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to
      100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p =
      0.01) than those given placebo. Logistic regression models revealed a
      significantly better response in sputum volume with fluticasone treatment than
      with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p =
      0.04), exacerbation frequency </=2/year (p = 0.04), and sputum purulence score >5
      (p = 0.03). CONCLUSIONS: ICS treatment is beneficial to patients with
      bronchiectasis, particularly those with P. aerurginosa infection.

PMID- 15741444
TI  - Vascular endothelial growth factor gene polymorphism and acute respiratory
      distress syndrome.
AB  - BACKGROUND: Non-cardiogenic pulmonary oedema is a characteristic feature of the
      acute respiratory distress syndrome (ARDS). The properties of vascular
      endothelial growth factor (VEGF) as a potent vascular permogen and mitogen have
      led to investigation of its potential role in this condition. Lower VEGF plasma
      levels have been linked to the presence of the T allele in the +936 CT
      polymorphism. We hypothesised that the presence of the T allele would be
      associated with the development and severity of ARDS. METHODS: A cohort of 137
      normal subjects, 117 ventilated patients with ARDS, and 103 "at risk" of ARDS
      were genotyped for the VEGF+936 CT polymorphism. The severity of physiological
      disturbance and mortality was determined in the ventilated cohorts. RESULTS: The
      CT and TT genotype frequencies were increased in ARDS patients compared with both
      normal subjects (OR 2.01, 95% CI 1.13 to 3.58, p = 0.02) and those "at risk" (OR
      2.05, 95% CI 1.02 to 2.20, p = 0.03). In patients with ARDS but not those "at
      risk", CT and TT genotypes were associated with a higher mean APACHE III score
      (80.9 (4.3) v 69.3 (2.9), p<0.05). CONCLUSION: These data support a role for VEGF
      in the pathogenesis of ARDS and its associated physiological derangement.

PMID- 15741445
TI  - Airway function and markers of airway inflammation in patients with treated
      hypothyroidism.
AB  - BACKGROUND: There is increasing evidence of an association between organ specific
      autoimmune diseases, particularly autoimmune thyroid disease and respiratory
      morbidity. A study was undertaken to determine whether patients with autoimmune
      thyroid disease have objective evidence of airway inflammation and dysfunction.
      METHODS: Twenty six non-smoking women with treated hypothyroidism and 19 non
      smoking controls completed a symptom questionnaire and underwent full lung
      function tests, capsaicin cough reflex sensitivity measurement, methacholine
      challenge test, and sputum induction over two visits. RESULTS: Symptoms of cough
      (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p =
      0.04) were reported more commonly in patients than controls. Patients with
      hypothyroidism had heightened cough reflex sensitivity compared with controls
      (geometric mean concentration of capsaicin causing five coughs: 40 v 108 mmol/l;
      mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to
      2.5; p = 0.008) and a significantly higher proportion of patients had airway
      hyperresponsiveness (methacholine provocative concentration (PC(20)) <8 mg/ml:
      38% v 0%; p = 0.016). Patients with hypothyroidism also had a significantly
      higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte
      count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p =
      0.048). CONCLUSION: Patients with treated hypothyroidism report more respiratory
      symptoms and have objective evidence of airway dysfunction and inflammation.

PMID- 15741446
TI  - Implantation of a pleurovenous shunt for massive chylothorax in a patient with
      yellow nail syndrome.
AB  - Yellow nail syndrome is a type of lymphatic dysplasia syndrome characterised by
      the triad of yellow nails, lymphoedema, and pleural effusions. The case history
      is presented of a 70 year old patient with yellow nail syndrome who complained of
      dyspnoea caused by massive chylothorax. The patient underwent insertion of a
      pleuroperitoneal shunt which resulted in abdominal distension and deterioration
      of leg oedema. The pleuroperitoneal shunt was replaced by a pleurovenous shunt on
      the right side which led to an improvement in the bilateral pleural effusions,
      abdominal distension, and leg oedema. A pleurovenous shunt may be an alternative
      rescue therapy for yellow nail syndrome.

PMID- 15741447
TI  - Surgery in early NSCLC and co-morbidity.

PMID- 15741448
TI  - Effect of oxygen on recovery from maximal exercise in COPD.

PMID- 15741449
TI  - EBC pH and chronic cough.

PMID- 15741450
TI  - Recruitment of ethnic minorities to asthma studies.

PMID- 15741451
TI  - Alpha1-antitrypsin genotype unaffected by age.

PMID- 15741452
TI  - Bilateral non-traumatic second rib fracture after bilateral first rib resection
      for TOS.

PMID- 15741453
TI  - Exhaled breath condensate in chronic cough.

PMID- 15741455
TI  - Bronchial beetle.

PMID- 15741456
TI  - Disconnection and cognitive dysmetria in schizophrenia.

PMID- 15741457
TI  - Toward a philosophical structure for psychiatry.
AB  - This article, which seeks to sketch a coherent conceptual and philosophical
      framework for psychiatry, confronts two major questions: how do mind and brain
      interrelate, and how can we integrate the multiple explanatory perspectives of
      psychiatric illness? Eight propositions are proposed and defended: 1) psychiatry
      is irrevocably grounded in mental, first-person experiences; 2) Cartesian
      substance dualism is false; 3) epiphenomenalism is false; 4) both brain-->mind
      and mind-->brain causality are real; 5) psychiatric disorders are etiologically
      complex, and no more "spirochete-like" discoveries will be made that explain
      their origins in simple terms; 6) explanatory pluralism is preferable to monistic
      explanatory approaches, especially biological reductionism; 7) psychiatry must
      move beyond a prescientific "battle of paradigms" to embrace complexity and
      support empirically rigorous and pluralistic explanatory models; 8) psychiatry
      should strive for "patchy reductionism" with the goal of "piecemeal integration"
      in trying to explain complex etiological pathways to illness bit by bit.

PMID- 15741458
TI  - Remission in schizophrenia: proposed criteria and rationale for consensus.
AB  - New advances in the understanding of schizophrenia etiology, course, and
      treatment have increased interest on the part of patients, families, advocates,
      and professionals in the development of consensus-defined standards for clinical
      status and improvement, including illness remission and recovery. As demonstrated
      in the area of mood disorders, such standards provide greater clarity around
      treatment goals, as well as an improved framework for the design and comparison
      of investigational trials and the subsequent evaluation of the effectiveness of
      interventions. Unlike the approach to mood disorders, however, the novel
      application of the concept of standard outcome criteria to schizophrenia must
      reflect the wide heterogeneity of its long-term course and outcome, as well as
      the variable effects of different treatments on schizophrenia symptoms. As an
      initial step in developing operational criteria, an expert working group reviewed
      available definitions and assessment instruments to provide a conceptual
      framework for symptomatic, functional, and cognitive domains in schizophrenia as
      they relate to remission of illness. The first consensus-based operational
      criteria for symptomatic remission in schizophrenia are based on distinct
      thresholds for reaching and maintaining improvement, as opposed to change
      criteria, allowing for alignment with traditional concepts of remission in both
      psychiatric and nonpsychiatric illness. This innovative approach for
      standardizing the definition for outcome in schizophrenia will require further
      examination of its validity and utility, as well as future refinement,
      particularly in relation to psychosocial and cognitive function and dysfunction.
      These criteria should facilitate research and support a positive, longer-term
      approach to studying outcome in patients with schizophrenia.

PMID- 15741459
TI  - Hippocampus, III: GABA-containing cell bodies and GAD mRNA.

PMID- 15741460
TI  - Heart transplant in a young man with schizophrenia.

PMID- 15741461
TI  - Jacques Joseph Moreau (1804-1884).

PMID- 15741462
TI  - "Gamma synchrony" in first-episode schizophrenia: a disorder of temporal
      connectivity?
AB  - OBJECTIVE: There has been a convergence of models describing schizophrenia as a
      disconnection syndrome, with a focus on the temporal connectivity of neural
      activity. Synchronous gamma-band (40-Hz) activity has been implicated as a
      candidate mechanism for the binding of distributed neural activity. To the
      authors' knowledge, this is the first study to investigate "gamma synchrony" in
      first-episode schizophrenia. METHOD: Forty medicated first-episode schizophrenia
      patients and 40 age- and sex-matched healthy comparison subjects participated in
      a conventional auditory oddball paradigm. Gamma synchrony, time-locked to target
      stimuli, was extracted from an ongoing EEG. The magnitude and latency of both
      early (gamma 1: -150 msec to 150 msec poststimulus) and late (gamma 2: 200 to 550
      msec poststimulus) synchrony were analyzed with multiple analysis of variance.
      RESULTS: First-episode schizophrenia patients showed a decreased magnitude and
      delayed latency for global gamma 1 synchrony in relation to healthy comparison
      subjects. By contrast, there were no group differences in gamma 2 synchrony.
      CONCLUSIONS: These findings suggest that first-episode schizophrenia patients
      have a global decrease and delay of temporal connectivity of neural activity in
      early sensory response to task-relevant stimuli. This is consistent with
      cognitive evidence of perceptual integration deficits in this disorder and raises
      the possibility that a breakdown in the early synchrony of distributed neural
      networks is a marker for the onset of schizophrenia.

PMID- 15741463
TI  - A concordance study of three electrophysiological measures in schizophrenia.
AB  - OBJECTIVE: The authors evaluated concordance rates among three
      electrophysiological measures in patients with schizophrenia, nonschizophrenic
      first-degree relatives of schizophrenia patients, and healthy comparison
      subjects. The purpose of the study was to provide data for defining a common
      endophenotype for genetic studies of schizophrenia and for improving the criteria
      for diagnosis. METHOD: P50 event-related potential inhibition, antisaccade, and
      smooth pursuit eye tracking paradigms were measured. Data for all three paradigms
      were available for 81 patients with schizophrenia, 25 parents of patients with
      schizophrenia, and 60 healthy comparison subjects. RESULTS: The schizophrenia
      patients and the patients' parents showed a high rate of inhibitory deficits
      measured by the P50 inhibition and antisaccade paradigms. Both groups had a high
      prevalence of eye tracking dysfunction. Smooth pursuit gain and the error rate in
      the antisaccade paradigm were significantly correlated in the schizophrenia
      patients and the parents, whereas P50 inhibition showed no correlation with
      smooth pursuit gain or antisaccade paradigm measurements. CONCLUSIONS: Despite
      superficial similarities, two paradigms designed to measure central inhibition
      processes (antisaccade and P50 inhibition) do not appear to reflect the same
      neurobiological substrates. In contrast, the convergence in performance data for
      the antisaccade and eye tracking paradigms suggests that the neural circuitry
      underlying these tasks may overlap. P50 inhibition and antisaccade errors were
      the optimal paradigms for discrimination between comparison subjects, patients
      with schizophrenia, and the parents of patients with schizophrenia.

PMID- 15741464
TI  - Specificity of prefrontal dysfunction and context processing deficits to
      schizophrenia in never-medicated patients with first-episode psychosis.
AB  - OBJECTIVE: Context processing is a cognitive construct associated with activity
      in the middle frontal gyrus. Schizophrenia-related deficits in context processing
      tasks have been associated with prefrontal cortical dysfunction. This study
      evaluated whether prefrontal cortical dysfunction related to context processing
      occurred in first-episode, never-medicated schizophrenia patients, whether this
      dysfunction also occurred in patients with nonschizophrenia psychosis, and
      whether this dysfunction was related to psychotic symptom expression. METHOD: A
      modified version of the AX continuous performance task was conducted during event
      related functional magnetic resonance imaging in 18 never-medicated, first
      episode schizophrenia patients, 12 never-medicated patients with first-episode
      nonschizophrenia psychosis, and 28 comparison participants without psychiatric
      disorder. RESULTS: In-scanner measures of errors and interference reaction time
      showed that the schizophrenia patients had a specific deficit in context
      processing. Trials with greater context processing demands corresponded to
      activity in the middle frontal gyrus (Brodmann's area 9) in the comparison
      subjects and in the patients with nonschizophrenia psychosis, but not in the
      schizophrenia patients. Individual differences in prefrontal cortical dysfunction
      were associated with context processing measures and disorganization symptoms.
      The schizophrenia patients also showed increased activity in the anterior
      (Brodmann's area 10) and inferior prefrontal cortices (Brodmann's area 45/46)
      when they were maintaining context over a delay. CONCLUSIONS: Prefrontal
      dysfunctions related to context processing were found only in schizophrenia
      patients early in the course of the illness, and these dysfunctions were related
      to disorganization symptoms. Instead of using context processing during a
      continuous performance task, schizophrenia patients may use an inefficient
      encoding and retrieval strategy.

PMID- 15741466
TI  - Predictive values of neurocognition and negative symptoms on functional outcome
      in schizophrenia: a longitudinal first-episode study with 7-year follow-up.
AB  - OBJECTIVE: The relationship between cognition and outcome in people with
      schizophrenia has been established in studies that, for the most part, examined
      chronic patients and were cross-sectional in design. The purpose of this study
      was to analyze the relationships between neurocognitive variables assessed at
      illness onset and functional outcome in a longitudinal design. An additional area
      of interest was whether the severity of negative symptoms would predict outcome
      independently from neurocognitive variables or whether there would be an overlap
      in their predictive power. METHOD: The authors administered a comprehensive
      cognitive battery and clinical assessments to 99 subjects who were in their first
      episode of illness and analyzed the relationship of cognition and symptom
      severity at intake with community outcome after an average follow-up period of 7
      years. RESULTS: Verbal memory, processing speed and attention, and the severity
      of negative symptoms at intake were related to subsequent outcome. Global
      psychosocial functioning was predicted by negative symptoms and attention. Verbal
      memory was the significant predictor of the degree of impairment in recreational
      activities. Impairment in relationships was predicted by negative symptoms and
      memory, whereas attention and negative symptoms were predictive of work
      performance. There was an overlap in the variance in outcome explained by
      cognitive variables and negative symptoms. CONCLUSIONS: Verbal memory and
      processing speed and attention are potential targets for psychosocial
      interventions to improve outcome. Results from cross-sectional or chronic patient
      studies do not necessarily correspond to the findings of this prospective first
      episode study in which cognition appears to explain less of the variance in
      outcome.

PMID- 15741465
TI  - Effects of psychotic state and task demand on prefrontal function in
      schizophrenia: an fMRI study of overt verbal fluency.
AB  - OBJECTIVE: Impaired prefrontal cortical function is regarded as a central feature
      of schizophrenia. Although many neuroimaging studies have found evidence of
      abnormal prefrontal activation when patients with schizophrenia perform cognitive
      tasks, the extent to which this abnormality depends on the presence of active
      psychotic symptoms and on the demands of the task is unclear. The authors tested
      the hypothesis that prefrontal functional abnormalities in schizophrenia would be
      more evident in patients with active psychosis than in patients who were in
      remission and would become more apparent in the face of increasing task demands.
      METHOD: The authors used functional magnetic resonance imaging (fMRI) to examine
      prefrontal cortical activity during a paced letter verbal fluency task in three
      groups of subjects: acutely psychotic patients with schizophrenia, schizophrenia
      patients in remission, and healthy volunteers. Online subject performance was
      measured by utilizing a clustered fMRI acquisition sequence that allowed overt
      verbal responses to be made in the relative absence of scanner noise. RESULTS:
      Patients with schizophrenia showed less activation than the healthy comparison
      subjects in the anterior cingulate and the inferior frontal and right middle
      frontal cortices, independent of psychotic state and task demand. Acutely
      psychotic patients showed less activation than the healthy comparison subjects,
      but these differences were less marked than the differences between the patients
      in remission and the healthy comparison subjects. Acutely psychotic patients had
      less activation than the comparison subjects in the anterior cingulate but no
      significant difference in lateral prefrontal activation. Increasing task demand
      led to greater anterior cingulate and middle frontal activation in patients with
      active psychosis than in patients in remission. CONCLUSIONS: Schizophrenia is
      associated with impaired prefrontal function, but its manifestation depends on
      the severity of psychotic symptoms and the level of task difficulty.

PMID- 15741467
TI  - Optimistic bias in the perception of personal risk: patterns in schizophrenia.
AB  - OBJECTIVE: Biases in the perception of personal vulnerability to risk could
      influence how individuals make decisions in many contexts. Schizophrenia
      patients, because of neurocognitive deficits and psychiatric symptoms, are often
      seen as compromised in their ability to appreciate risk information and in their
      decision-making capacity. The authors investigated whether schizophrenia patients
      share the same optimistic biases frequently demonstrated by non-ill adults in
      their perceptions of personal risk. METHOD: Twenty-five schizophrenic outpatients
      and 23 healthy comparison subjects completed a risk perception questionnaire on
      which they compared their own likelihood of experiencing adverse events to that
      of other adults. Questionnaire items were adverse events of three types:
      controllable, uncontrollable, and neutral. The degree to which subjects rated
      their own likelihood of experiencing adverse events as lower than others' was an
      index of optimistic bias. RESULTS: Although both groups showed an optimistic bias
      in general, healthy comparison subjects demonstrated a greater level of optimism
      than did schizophrenia patients, especially for events typically perceived as
      controllable. Psychiatric symptoms rated with the Brief Psychiatric Rating Scale
      and the Scale for the Assessment of Negative Symptoms bore little relationship to
      patients' ratings on the risk questionnaire. CONCLUSIONS: Results showed that an
      unrealistically optimistic bias in the perception of personal risk was at least
      as evident in a healthy comparison group as in a schizophrenia group. Such a bias
      could influence decision making. By identifying and responding to such biases,
      clinicians and researchers can promote more fully informed and rational decisions
      in patients and healthy adults.

PMID- 15741468
TI  - Extensions of errorless learning for social problem-solving deficits in
      schizophrenia.
AB  - OBJECTIVE: There is a clear need to develop psychosocial rehabilitation methods
      that compensate for neurocognitive deficits common to persons with severe and
      persistent mental illness. Errorless learning, a compensatory training
      intervention, has been successful in teaching entry-level job tasks. However,
      errorless learning's applicability to broader, more complex functions is unknown.
      The present study tested the extension of errorless learning for deficits in
      social problem-solving skills in patients with schizophrenia. METHOD: Sixty
      clinically stable outpatients with schizophrenia or schizoaffective disorder were
      stratified by gender and level of memory impairment before being randomly
      assigned to one of two training programs: errorless learning or symptom
      management. Groups were matched for training time, format and structure of
      training, and types of teaching aids used. Social problem-solving ability,
      measured by the Assessment of Interpersonal Problem-Solving Skills, was assessed
      at baseline, within 2 days of training completion, and after 3 months. Dependent
      measures were the scores for the receiving, processing, and sending skills areas
      from the Assessment of Interpersonal Problem-Solving Skills. RESULTS: A repeated
      measures analysis of covariance was conducted for each dependent measure with
      baseline Assessment of Interpersonal Problem-Solving Skills score entered as a
      covariate. For all three skills, there was a significant training group effect
      favoring errorless learning. Durability of errorless learning training effects
      extended to the 3-month follow-up assessment for processing and sending skills
      but not receiving skills. CONCLUSIONS: Results support the extension of errorless
      learning to complex functions such as social problem-solving skills in the
      rehabilitation of persons with schizophrenia.

PMID- 15741469
TI  - A randomized, controlled trial of cognitive behavioral social skills training for
      middle-aged and older outpatients with chronic schizophrenia.
AB  - OBJECTIVE: The number of older patients with chronic schizophrenia is increasing.
      There is a need for empirically validated psychotherapy interventions for these
      patients. Cognitive behavioral social skills training teaches cognitive and
      behavioral coping techniques, social functioning skills, problem solving, and
      compensatory aids for neurocognitive impairments. The authors compared treatment
      as usual with the combination of treatment as usual plus cognitive behavioral
      social skills training. METHOD: The randomized, controlled trial included 76
      middle-aged and older outpatients with chronic schizophrenia, who were assigned
      to either treatment as usual or combined treatment. Cognitive behavioral social
      skills training was administered over 24 weekly group sessions. Blind raters
      assessed social functioning, psychotic and depressive symptoms, cognitive
      insight, and skill mastery. RESULTS: After treatment, the patients receiving
      combined treatment performed social functioning activities significantly more
      frequently than the patients in treatment as usual, although general skill at
      social functioning activities did not differ significantly. Patients receiving
      cognitive behavioral social skills training achieved significantly greater
      cognitive insight, indicating more objectivity in reappraising psychotic
      symptoms, and demonstrated greater skill mastery. The overall group effect was
      not significant for symptoms, but the greater increase in cognitive insight with
      combined treatment was significantly correlated with greater reduction in
      positive symptoms. CONCLUSIONS: With cognitive behavioral social skills training,
      middle-aged and older outpatients with chronic schizophrenia learned coping
      skills, evaluated anomalous experiences with more objectivity (achieved greater
      cognitive insight), and improved social functioning. Additional research is
      needed to determine whether cognitive insight mediates psychotic symptom change
      in cognitive behavior therapy for psychosis.

PMID- 15741470
TI  - Posttraumatic stress and depressive reactions among children and adolescents
      after the 1999 earthquake in Ano Liosia, Greece.
AB  - OBJECTIVE: This study evaluated the severity of posttraumatic stress and
      depressive reactions among children and adolescents 3 months after the 1999
      earthquake in Ano Liosia, Greece, and additionally assessed the relationship of
      these reactions to objective and subjective features of earthquake exposure, sex,
      school level, postearthquake difficulties, death of a family member, and thoughts
      of revenge. METHOD: This school-based study of 1,937 students was conducted in
      two differentially exposed cities (Ano Liosia, at the epicenter, and Dafni, 10
      kilometers from the epicenter) with an earthquake exposure questionnaire, the
      UCLA Posttraumatic Stress Disorder (PTSD) Reaction Index, and the Depression Self
      Rating Scale. RESULTS: Endorsement of earthquake-related exposure items between
      the two cities was congruent with the extent of earthquake impact in each city.
      Median PTSD Reaction Index scores were significantly higher in Ano Liosia. The
      estimated rates of PTSD and clinical depression for both cities combined were
      4.5% and 13.9%, respectively. Depression, subjective and objective earthquake
      related experiences, and difficulties at home accounted for 41% of the variance
      in severity of PTSD reactions. PTSD score was the single most powerful variable
      predicting depression (36% of the variance), with only sex making a small but
      significant additional contribution. CONCLUSIONS: This study demonstrated the
      feasibility of conducting large-scale school-based postdisaster mental health
      screening for planning intervention strategies. The present findings regarding
      PTSD and depression indicate the need to provide targeted specialized
      postdisaster mental health services to subgroups with significant levels of
      posttraumatic stress and depressive reactions after an earthquake of moderate
      intensity.

PMID- 15741471
TI  - Is posttraumatic stress in youth a culture-bound phenomenon? A comparison of
      symptom trends in selected U.S. and Russian communities.
AB  - OBJECTIVE: The cross-cultural applicability of the concept of posttraumatic
      stress was investigated by assessing symptom frequency and levels of comorbid
      psychopathology in adolescents from the United States and Russia. METHOD: A self
      report survey was conducted in representative samples of 2,157 adolescents 14 to
      17 years old from urban communities of the United States (N=1,212) and Russia
      (N=945). RESULTS: In both countries, the levels of all three major clusters of
      posttraumatic symptoms (reexperiencing, avoidance, and arousal), as well as of
      internalizing psychopathology, increased along with the level of posttraumatic
      stress. Expectations about the future had a tendency to decrease with increasing
      posttraumatic stress. No differences between countries in significant interaction
      effects for symptom levels were found. CONCLUSIONS: The current findings suggest
      that posttraumatic symptoms and their associations with other adolescent mental
      health problems are not culture bound and that the psychological consequences of
      trauma follow similar dynamics cross-culturally.

PMID- 15741472
TI  - The role of peritraumatic dissociation and gender in the association between
      trauma and mental health in a Palestinian community sample.
AB  - OBJECTIVE: This research focused on gender-specific trauma exposure and mental
      health symptoms among Palestinians living in conditions of military violence. It
      also examined the gender-specific role of peritraumatic dissociation in
      moderating the association between lifetime trauma and mental health. METHOD: A
      random sample of 311 Palestinian women and 274 men ages 16-60 years from the Gaza
      Strip participated. The subjects were asked about lifetime trauma and
      peritraumatic dissociation during their most severe traumatic experience. Mental
      health was indicated by total scores and diagnostic variables of posttraumatic
      stress disorder (PTSD), anxiety, mood (depression), and somatization disorders.
      Symptoms of hostility were assessed as a total score. RESULTS: The women reported
      a lower level of lifetime trauma than the men, but exposure to trauma was
      associated with PTSD among both genders. Exposure to lifetime trauma was further
      associated with anxiety, mood, and somatoform disorders only among women but not
      among men. No gender differences were found in the level of peritraumatic
      dissociation. Analyses on moderating effects showed that peritraumatic
      dissociation made both men and women more vulnerable to symptoms of hostility and
      men to depressive symptoms when they were exposed to lifetime trauma.
      CONCLUSIONS: The results are consistent with previous studies in more peaceful
      conditions: men experience more traumatic events, whereas exposure is associated
      with more severe psychiatric disorders among women. Peritraumatic dissociation as
      an acute response to trauma constituted a risk for mental health symptoms in both
      genders.

PMID- 15741473
TI  - Specialized inpatient trauma treatment for adults abused as children: a follow-up
      study.
AB  - OBJECTIVE: The authors investigated outcome at discharge and at follow-up
      assessments for adults abused as children who completed a 6-week inpatient
      program for traumatic stress recovery. METHOD: Participants were assessed at
      admission, discharge, and 3, 6, and 12 months postdischarge on measures of global
      symptom severity, posttraumatic stress disorder (PTSD), and disrupted beliefs.
      Two wait-list comparison groups were also assessed at two points in time for
      comparison with the discharge and 3-month postdischarge assessments of the
      treatment group. RESULTS: Relative to admission, the mean scores on all outcome
      measures for the treatment group were improved at discharge and at 6 and 12
      months. Relative to a wait list group, the treatment group was significantly
      improved at discharge. After 3 months, the scores for the treatment group were
      not different from those of a wait list group because of deterioration in the
      treatment group. Age, source of income, and number of axis II disorders were
      associated with differing patterns of PTSD symptom change over time. Between 32%
      and 45%, depending on outcome measure, met stringent criteria for clinically
      significant change at 12 months postdischarge. CONCLUSIONS: At discharge from a
      specialized inpatient treatment program, adults with a history of abuse during
      childhood showed improvement relative to a wait list group. Scores tended to
      deteriorate in the 3 months following discharge but rebounded to discharge levels
      by 12 months postdischarge. Although many abused adults benefited from
      specialized inpatient treatment, a substantial proportion did not show clinically
      significant change 1 year later.

PMID- 15741475
TI  - Regional cerebral blood flow responses to smoking in tobacco smokers after
      overnight abstinence.
AB  - OBJECTIVE: The purpose of the study was to determine the effects of cigarette
      smoking on brain regional function in a group of chronic smokers by using
      cerebral blood flow (CBF) measures and positron emission tomography (PET).
      METHOD: Nineteen tobacco smokers were studied after about 12 hours of smoking
      abstinence. Regional CBF (rCBF) measures were obtained with PET and [15O]H2O in
      six consecutive scans. Two average-nicotine-yield (1.0 mg) and one denicotinized
      (0.08 mg) research cigarettes with similar tar yields (9.5 mg and 9.1 mg,
      respectively) were smoked in a double-blind design, preceded and followed by
      baseline scans. The rCBF effects of smoking were compared to baseline measures
      and between cigarettes, as well as to subjective ratings of craving for
      cigarettes. RESULTS: Smoking the first cigarette of the day resulted in increases
      in rCBF in the visual cortex and the cerebellum and reductions in the anterior
      cingulate, the right hippocampus, and the ventral striatum, including the nucleus
      accumbens. Cigarette craving scores correlated with rCBF changes in the dorsal
      anterior cingulate and right hippocampus. Less pronounced effects were observed
      with the second cigarette and the denicotinized cigarette. CONCLUSIONS: Smoking
      affects rCBF not only in areas of the brain rich in nicotinic cholinergic
      receptors but also in areas implicated in the rewarding effects of drugs of
      abuse. Furthermore, craving for a cigarette in chronic smokers was correlated
      with rCBF in the right hippocampus, an area involved in associating environmental
      cues with drugs, and in the left dorsal anterior cingulate, an area implicated in
      drug craving and relapse to drug-seeking behavior.

PMID- 15741474
TI  - Posttraumatic stress disorder comorbid with major depression: factors mediating
      the association with suicidal behavior.
AB  - OBJECTIVE: The purpose of the study was to determine if patients with a history
      of major depressive episode and comorbid posttraumatic stress disorder (PTSD)
      have a higher risk for suicide attempt and differ in other measures of suicidal
      behavior, compared to patients with major depressive episode but no PTSD. In
      addition, to explore how PTSD comorbidity might increase risk for suicidal
      behavior in major depressive episode, the authors investigated the relationship
      between PTSD, cluster B personality disorder, childhood sexual or physical abuse,
      and aggression/impulsivity. METHOD: The subjects were 230 patients with a
      lifetime history of major depressive episode; 59 also had lifetime comorbid PTSD.
      The demographic and clinical characteristics of subjects with and without PTSD
      were compared. Multivariate analysis was used to examine the relationship between
      suicidal behavior and lifetime history of PTSD, with adjustment for clinical
      factors known to be associated with suicidal behavior. RESULTS: Patients with a
      lifetime history of PTSD were significantly more likely to have made a suicide
      attempt. The groups did not differ with respect to suicidal ideation or intent,
      number of attempts made, or maximum lethality of attempts. The PTSD group had
      higher objective depression, impulsivity, and hostility scores; had a higher rate
      of comorbid cluster B personality disorder; and were more likely to report a
      childhood history of abuse. However, cluster B personality disorder was the only
      independent variable related to lifetime suicide attempts in a multiple
      regression model. CONCLUSIONS: PTSD is frequently comorbid with major depressive
      episode, and their co-occurrence enhances the risk for suicidal behavior. A
      higher rate of comorbid cluster B personality disorder appears to be a salient
      factor contributing to greater risk for suicidal acts in patients with a history
      of major depressive episode who also have PTSD, compared to those with major
      depressive episode alone.

PMID- 15741476
TI  - Comparison of large versus smaller randomized trials for mental health-related
      interventions.
AB  - OBJECTIVE: The extent of disagreement between large and smaller randomized,
      controlled trials on mental health issues is unknown. The authors aimed to
      compare the results of large versus smaller trials on mental health-related
      interventions. METHOD: The authors screened 161 Cochrane and 254 Database of
      Abstracts of Reviews of Effectiveness systematic reviews on mental health-related
      interventions. They identified 16 meta-analyses with at least one "large"
      randomized trial with sample size >800 and at least one "smaller" trial. Effect
      sizes were calculated separately for large and smaller trials. Heterogeneity was
      assessed between all studies, within each group (large and smaller studies), and
      between large and smaller studies. RESULTS: Significant between-study
      heterogeneity was seen in five meta-analyses. By random-effects calculations, the
      results of large and smaller trials differed beyond chance in four meta-analyses
      (25%). In three of these disagreements (effect of day care on IQ, discontinuation
      of antidepressants, risperidone versus typical antipsychotics for schizophrenia),
      the smaller trials showed greater effect sizes than the large trials. The inverse
      was seen in one case (olanzapine versus typical antipsychotics for
      schizophrenia). With fixed-effects models, disagreements beyond chance occurred
      in five cases (31%). In four meta-analyses, the effect size differed over twofold
      between large and smaller trials. Various quality and design parameters were
      identified as potential explanations for some disagreements. CONCLUSIONS: Large
      trials are uncommon in mental health. Their results are usually comparable with
      the results of smaller studies, but major disagreements do occur. Both large and
      smaller trials should be scrutinized as they offer a continuum of randomized
      evidence.

PMID- 15741477
TI  - The occupational burden of mental disorders in theU.S. military: psychiatric
      hospitalizations, involuntary separations, and disability.
AB  - OBJECTIVE: A recent study showed that among U.S. military personnel, mental
      disorders were the leading medical correlate of separation from military service.
      The reasons for this association have not been determined. The purpose of this
      study was to characterize the risk and reasons for service separation for
      soldiers hospitalized with mental disorders compared with those hospitalized for
      other illnesses. METHOD: Population-based electronic health care data were linked
      with data on separations and disability. The authors constructed a cohort of
      13,971 U.S. Army soldiers first hospitalized in 1998 and followed them for up to
      2 years following this first hospitalization. RESULTS: The rate of service
      separation 6 months after first hospitalization was 45% among personnel whose
      primary hospital discharge diagnosis was a mental disorder, 27% among those with
      a secondary mental disorder discharge diagnosis, and 11% among those hospitalized
      for all other medical conditions. Separation from military service due to medical
      disability, misconduct and other legal problems, unauthorized work absences,
      behavior related to personality disorders, and alcohol rehabilitation failure was
      significantly more common following hospitalization for a mental disorder than
      for other medical conditions. Mental disorders were also significantly associated
      with medical separations in which there was evidence that the condition existed
      prior to service. CONCLUSIONS: In the military, the occupational impact of mental
      disorders compared with other medical conditions appears to be mediated not only
      by greater disease chronicity and severity but also by a variety of behavioral
      problems including misconduct, legal problems, unauthorized absences, and
      alcohol/drug-related problems. The study also points to the difficulties inherent
      in screening for mental disorders prior to entry into military service.

PMID- 15741478
TI  - Psychiatric disorders in young adult intercountry adoptees: an epidemiological
      study.
AB  - OBJECTIVE: The prevalences of psychiatric disorders in young adult intercountry
      adoptees and nonadopted young adults from the general population were compared.
      METHOD: In the Netherlands, a total of 1,484 young adult intercountry adoptees
      (72.5% of the original sample at age 10-15 years) and 695 nonadopted subjects
      (78.1% of the original sample) of comparable age from the general population were
      interviewed by using a standardized psychiatric interview generating DSM-IV
      diagnoses. RESULTS: The adopted young adults were 1.52 times as likely to meet
      the criteria for an anxiety disorder as the nonadopted young adults; the 95%
      confidence interval (CI) was 1.15-2.00. The adoptees were 2.05 (95% CI=1.32-3.17)
      times as likely to meet the criteria for substance abuse or dependence. The
      adopted men were 3.76 (95% CI=1.69-8.37) times as likely to have a mood disorder
      as nonadopted men, while for women there was no significant difference between
      adoptees and nonadoptees. No significant difference for the diagnosis of
      disruptive disorder was found. For all diagnoses together, adoptees with low and
      middle parental socioeconomic status in childhood did not differ from the
      comparison subjects, while adoptees with high parental socioeconomic status were
      2.17 times (95% CI=1.50-3.13) as likely to meet the criteria for a disorder as
      nonadoptees with high parental socioeconomic status. CONCLUSIONS: Intercountry
      adoptees run a higher risk of having severe mental health problems in adulthood
      than nonadoptees of the same age. The risk of later malfunctioning differs for
      different disorders and different groups of adoptees.

PMID- 15741479
TI  - Association between reduced extraversion and right posterior fusiform gyrus gray
      matter reduction in chronic schizophrenia.
AB  - OBJECTIVE: The authors examined the association between volume of the fusiform
      gyrus, a region involved in face processing, and the personality trait of
      extraversion in patients with schizophrenia. METHOD: Male patients (N=24) and age
      matched male comparison subjects (N=26) completed NEO Five-Factor Inventory
      personality measures of extraversion and underwent high-spatial-resolution
      magnetic resonance imaging of anterior and posterior fusiform gyrus gray matter.
      RESULTS: Low extraversion scores were significantly correlated with gray matter
      volume reductions in the right posterior fusiform gyrus for patients but not
      comparison subjects. CONCLUSIONS: Reduced right posterior fusiform gyrus volume
      may contribute to disease-related social disturbances, characterized by both low
      extraversion and reduced sensitivity to human faces.

PMID- 15741480
TI  - White matter abnormalities in first-episode schizophrenia or schizoaffective
      disorder: a diffusion tensor imaging study.
AB  - OBJECTIVE: The goal of this study was to investigate brain white matter
      abnormalities by using diffusion tensor imaging in patients with schizophrenia or
      schizoaffective disorder close to illness onset. METHOD: Ten patients
      experiencing a first episode of schizophrenia or schizoaffective disorder and 13
      healthy volunteers received diffusion tensor imaging and structural magnetic
      resonance imaging examinations. Voxel-wise analysis was used to compare
      fractional anisotropy maps in the white matter of the two groups following
      intersubject registration to Talairach space. RESULTS: Compared with healthy
      volunteers, patients demonstrated lower fractional anisotropy in the left
      internal capsule and left-hemisphere white matter of the middle frontal gyrus and
      posterior superior temporal gyrus. There were no areas of significantly higher
      fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS:
      These findings suggest that white matter pathology is present early in the course
      of schizophrenia and may be less pronounced than has been found in previous
      diffusion tensor imaging studies of patients with chronic illness. Further, these
      data are consistent with hypotheses regarding frontotemporal dysfunction and the
      failure of left-hemisphere lateralization in the pathophysiology of
      schizophrenia.

PMID- 15741481
TI  - A three-dimensional morphometric study of craniofacial shape in schizophrenia.
AB  - BACKGROUND: Subtle dysmorphogenesis of the craniofacial region constitutes
      important corroborating evidence of the neurodevelopmental origins of
      schizophrenia. Advances in facial visualization now allow for three-dimensional
      anthropometric evaluations of potentially greater discriminatory power in
      examining the complex geometric relationships of facial topography. METHOD: Sixty
      five anthropometrically derived landmarks were identified from three-dimensional
      facial images collected from 14 patients with schizophrenia and 11 comparison
      subjects, imaged with a high-resolution, portable laser scanner. RESULTS: Using
      the Procrustes morphometric approach for shape analysis, the difference in mean
      shapes was highly significant, with patients exhibiting superoinferior elongation
      of the face. CONCLUSIONS: The topography of craniofacial anomalies in
      schizophrenia is not random and points to midline deformation.

PMID- 15741483
TI  - Low gene expression conferred by association of an allele of the 5-HT2C receptor
      gene with antipsychotic-induced weight gain.
AB  - OBJECTIVE: Association has been reported between the C allele of a -759C/T
      polymorphism in the promoter of the 5-HT2C receptor gene (HTR2C) and
      antipsychotic-induced weight gain, suggesting that polymorphic HTR2C expression
      influences this phenotype. The authors tested this polymorphism, and other
      promoter variants, for effects on HTR2C transcription. METHOD: Six HTR2C promoter
      haplotypes constructed from four polymorphisms were cloned into a luciferase
      reporter gene plasmid. Their transcriptional activities were then compared in two
      human cell lines. RESULTS: All haplotypes containing the -759C allele showed less
      transcriptional activity than haplotypes containing the -759T allele. The A
      allele of a -997G/A polymorphism was also associated with reduced expression.
      CONCLUSIONS: These findings suggest that the -759C allele is functional and
      results in relative underexpression of HTR2C. Reduced expression of HTR2C mRNA
      may underlie vulnerability to weight gain following antipsychotic treatment.

PMID- 15741482
TI  - Association of a functional polymorphism in the serotonin transporter gene with
      abnormal emotional processing in ecstasy users.
AB  - OBJECTIVE: The long-term effects of the use of 3,4-methylenedioxymethamphetamine
      (MDMA, or Ecstasy) in humans are controversial and unclear. The authors' goal was
      to assess the contribution of a functional polymorphism in the gene encoding
      serotonin transporter to changes in emotional processing following chronic
      Ecstasy use. METHOD: They investigated Beck Depression Inventory scores and
      performance on the Affective Go/No-Go test, a computerized neuropsychological
      test sensitive to emotional processing, in Ecstasy users and comparison subjects,
      stratifying the results by serotonin transporter genotype. RESULTS: Ecstasy use
      was associated with higher Beck Depression Inventory score and abnormalities in
      the Affective Go/No-Go test in individuals with the ss and ls genotype but not
      those with the ll genotype. CONCLUSIONS: Ecstasy users carrying the s allele, but
      not comparison subjects carrying the s allele, showed abnormal emotional
      processing. On the basis of a comparison with acute tryptophan depletion, the
      authors hypothesize that chronic Ecstasy use may cause long-term changes to the
      serotonin system, and that Ecstasy users carrying the s allele may be at
      particular risk for emotional dysfunction.

PMID- 15741484
TI  - Aberrant intracellular calcium signaling in olfactory neurons from patients with
      bipolar disorder.
AB  - OBJECTIVE: The authors examined the feasibility of using olfactory receptor
      neurons from living patients to test whether calcium signaling is altered in a
      neuronal cell population in bipolar disorder. METHOD: Ratiometric fluorescence
      photomicroscopy was used to assess basal and stimulus-induced changes in
      intracellular calcium levels in biopsy-derived olfactory receptor neurons from
      seven euthymic patients with bipolar disorder who were medication-free, 10
      euthymic patients with bipolar disorder who were treated with mood stabilizers,
      and 17 age- and sex-matched comparison subjects without bipolar disorder.
      RESULTS: Olfactory receptor neurons from the seven medication-free patients
      responded to stimuli predominantly with decreases in intracellular calcium,
      unlike those from the seven matched healthy subjects. Olfactory receptor neurons
      from patients treated with mood stabilizers were less likely to respond to
      stimulation than olfactory receptor neurons from medication-free patients.
      CONCLUSIONS: This study demonstrates the feasibility of using olfactory receptor
      neurons to examine alterations in intracellular signaling in neuronal cells from
      living patients. Our results, although based on a small number of subjects,
      suggest that altered intracellular calcium signaling in olfactory receptor
      neurons may be a trait of bipolar disorder.

PMID- 15741485
TI  - Is cigarette smoking associated with suicidal ideation among young people?
AB  - OBJECTIVE: The authors examined the association between suicidal ideation in
      early adulthood and daily tobacco smoking in a community sample of adolescents.
      METHOD: Participants were enrolled in a longitudinal study of health and
      development. The factors of disadvantage, impulsiveness, stress, depressed mood,
      tobacco smoking, other substance use, and parental attachment were included in
      multivariate modelling of suicidal ideation. RESULTS: Data on tobacco use were
      available for 764 participants. Early tobacco smoking was significantly
      predictive of later suicidal ideation, but there was no longer a significant
      relationship when high levels of stress and depression and low levels of parental
      attachment in adolescence were included in the multivariate model. CONCLUSIONS:
      Tobacco smoking in adolescence does not appear to elevate the risk of later
      suicidal ideation.

PMID- 15741486
TI  - Impact of trait impulsivity and state aggression on divalproex versus placebo
      response in borderline personality disorder.
AB  - OBJECTIVE: The authors' goal was to determine whether specific pretreatment
      clinical characteristics differentially predict favorable treatment response to
      divalproex versus placebo for impulsive aggression in patients with borderline
      personality disorder. METHOD: Fifty-two outpatients with DSM-IV borderline
      personality disorder were randomly assigned to receive divalproex (N=20) or
      placebo (N=32), double-blind, for 12 weeks. Trait impulsivity symptoms were
      determined by using the Barratt Impulsiveness Scale, and state aggression
      symptoms were determined by using the Overt Aggression Scale modified for
      outpatients. Affective stability was determined by using the Young Mania Rating
      Scale and the Hamilton Depression Rating Scale. Analyses were performed to
      identify possible baseline symptom domains that predict treatment response.
      RESULTS: Divalproex was superior to placebo in reducing impulsive aggression in
      patients with borderline personality disorder. Divalproex-treated patients
      responded better than placebo-treated patients among those with higher baseline
      trait impulsivity symptoms and state aggression symptoms. The effects of baseline
      trait impulsivity and state aggression appear to be independent of one another.
      However, baseline affective instability did not influence differential treatment
      response. CONCLUSIONS: Both pretreatment trait impulsivity symptoms and state
      aggression symptoms predict a favorable response to divalproex relative to
      placebo for impulsive aggression in patients with borderline personality
      disorder.

PMID- 15741487
TI  - Ziprasidone-induced acute dystonia.

PMID- 15741488
TI  - Aripiprazole in a patient vulnerable to side effects.

PMID- 15741489
TI  - Aripiprazole and depression in schizoaffective disorder.

PMID- 15741490
TI  - Memantine and catatonic schizophrenia.

PMID- 15741491
TI  - Cognition, copyright, and the classroom.

PMID- 15741492
TI  - Benztropine equivalents for antimuscarinic medication.

PMID- 15741493
TI  - Interview quality and signal detection in clinical trials.

PMID- 15741494
TI  - Stress disorder after traumatic injury.

PMID- 15741495
TI  - Amygdala morphometry in affective disorders.

PMID- 15741496
TI  - Monotherapy versus polypharmacy for hospitalized psychiatric patients.

PMID- 15741497
TI  - Monotherapy versus polypharmacy for hospitalized psychiatric patients.

PMID- 15741498
TI  - Monotherapy versus polypharmacy for hospitalized psychiatric patients.

PMID- 15741499
TI  - Neurotensin receptor agonists and antagonists for schizophrenia.

PMID- 15741500
TI  - Nonsignificant but suggestive results?

PMID- 15741501
TI  - Completed suicide after a suicide attempt.

PMID- 15741503
TI  - Retinoids potentiate peroxisome proliferator-activated receptor gamma action in
      differentiation, gene expression, and lipid metabolic processes in developing
      myeloid cells.
AB  - Nuclear hormone receptors have been shown to be important transcription factors
      for regulating lipid metabolism in myeloid cells and were also implicated in
      differentiation processes of the myeloid lineage and macrophages. Peroxisome
      proliferator-activated receptor gamma (PPARgamma) seems to be a key component of
      lipid uptake by inducing the scavenger receptor CD36 that mediates oxidized low
      density lipoprotein uptake in macrophages. Retinoic acid receptors, on the other
      hand, were also shown to play important roles in myeloid cell differentiation. In
      this study, we present evidence for a cross-talk between these two nuclear
      receptor pathways in myeloid cells. We show that expression level of PPARgamma
      increases with the degree of monocyte/macrophage commitment during maturation.
      Activation of PPARgamma leads to the increased expression of maturation markers
      (e.g., CD14, CD36). It is interesting that retinoid treatment potentiates
      PPARgamma's ability to induce transcription of its target genes. Retinoid
      increased PPARgamma response is sufficient for enhancing lipid uptake. Our data,
      taken together, indicate that the expression level of PPARgamma increases during
      monocyte/macrophage development. PPARgamma activity can be enhanced by retinoids
      at least in part via increasing PPARgamma expression level. These observations
      can be exploited to enhance therapeutically beneficial PPAR responses in myeloid
      cells.

PMID- 15741502
TI  - Neurotensin receptor agonists and antagonists for schizophrenia.

PMID- 15741504
TI  - Phylogeny of Na+/Ca2+ exchanger (NCX) genes from genomic data identifies new gene
      duplications and a new family member in fish species.
AB  - The Na+/Ca2+ exchanger (NCX) is a member of the cation/Ca2+ antiporter (CaCA)
      family and plays a key role in maintaining cellular Ca2+ homeostasis in a variety
      of cell types. NCX is present in a diverse group of organisms and exhibits high
      overall identity across species. To date, three separate genes, i.e., NCX1, NCX2,
      and NCX3, have been identified in mammals. However, phylogenetic analysis of the
      exchanger has been hindered by the lack of nonmammalian NCX sequences. In this
      study, we expand and diversify the list of NCX sequences by identifying NCX
      homologs from whole-genome sequences accessible through the Ensembl Genome
      Browser. We identified and annotated 13 new NCX sequences, including 4 from
      zebrafish, 4 from Japanese pufferfish, 2 from chicken, and 1 each from honeybee,
      mosquito, and chimpanzee. Examination of NCX gene structure, together with
      construction of phylogenetic trees, provided novel insights into the molecular
      evolution of NCX and allowed us to more accurately annotate NCX gene names. For
      the first time, we report the existence of NCX2 and NCX3 in organisms other than
      mammals, yielding the hypothesis that two serial NCX gene duplications occurred
      around the time vertebrates and invertebrates diverged. In addition, we have
      found a putative new NCX protein, named NCX4, that is related to NCX1 but has
      been observed only in fish species genomes. These findings present a stronger
      foundation for our understanding of the molecular evolution of the NCX gene
      family and provide a framework for further NCX phylogenetic and molecular
      studies.

PMID- 15741505
TI  - Differential gene expression in pulmonary artery endothelial cells exposed to
      sickle cell plasma.
AB  - Clinical variability in sickle cell disease (SCD) suggests a role for extra
      erythrocytic factors in the pathogenesis of vasoocclusion. We hypothesized that
      endothelial cell (EC) dysfunction, one possible modifier of disease variability,
      results from induction of phenotypic changes by circulating factors. Accordingly,
      we analyzed gene expression in cultured human pulmonary artery ECs (HPAEC)
      exposed to plasma from 1) sickle acute chest syndrome (ACS) patients, 2) SCD
      patients at steady state, 3) normal volunteers, and 4) serum-free media, using
      whole genome microarrays (U133A-B GeneChip, Affymetrix). Data were analyzed by
      Bayesian analysis of differential gene expression (BADGE). Differential
      expression was defined by the probability of >1.5 fold change in signal intensity
      greater than 0.999 and a predicted score of 70-100, measured by cross-validation.
      Compared with normal plasma, plasma from SCD patients (steady state) resulted in
      differential expression of 50 genes in HPAEC. Of these genes, molecules involved
      in cholesterol biosynthesis and lipid transport, the cellular stress response,
      and extracellular matrix proteins were most prominent. Another 58 genes were
      differentially expressed in HPAEC exposed to plasma from ACS patients. The
      pattern of altered gene expression suggests that plasma from SCD patients induces
      an EC phenotype which is anti-apoptotic and favors cholesterol biosynthesis. An
      altered EC phenotype elicited by SCD plasma may contribute to the pathogenesis of
      sickle vasoocclusion.

PMID- 15741506
TI  - Homocysteine levels in A/J and C57BL/6J mice: genetic, diet, gender, and parental
      effects.
AB  - Increased levels of homocysteine in the blood have been associated with various
      birth defects and adult diseases. However, the extent to which genetic factors
      control homocysteine levels in healthy individuals is unclear. Laboratory mice
      are valuable models for dissecting the genetic and environmental controls of
      total homocysteine (tHcy) levels. We assessed the inheritance of tHcy levels in
      two inbred strains, A/J and C57BL/6J (B6), under controlled physiological
      conditions and assessed the relative importance of genetic, diet, gender, and
      parental effects. Diet affected mean tHcy levels, whereas gender affected both
      the mean and variance of tHcy levels. Moreover, gender of the parents influenced
      mean tHcy levels in reciprocal F1 hybrids, suggesting maternal effects. Finally,
      gene-diet interactions affected heritability of mean tHcy levels. These studies
      showed that each of these factors contributes to tHcy levels and provided
      important clues to understanding homocysteine homeostasis in humans.

PMID- 15741507
TI  - A quantitative trait locus for aortic smooth muscle cell number acting
      independently of blood pressure: implicating the angiotensin receptor AT1B gene
      as a candidate.
AB  - Vascular hyperplasia may be involved in the remodeling of vasculature. It was
      unknown whether there were genetic determinants for aortic smooth muscle cell
      number (SMCN) and, if so, whether they acted independently of those for blood
      pressure (BP). To unravel this issue, we utilized congenic strains previously
      constructed for BP studies. These strains were made by replacing various
      chromosome 2 segments of the Dahl salt-sensitive (S) rat with those of the Milan
      normotensive rat (MNS). We measured and compared SMCN in aortic cross-sectional
      areas and BPs of these strains. Consequently, a quantitative trait locus (QTL)
      for SMCN was localized to a chromosome region not containing a BP QTL, but
      harboring the locus for the angiotensin II receptor AT1B (Agtr1b). Agtr1b became
      a candidate for the SMCN QTL because 1) two significant mutations were found in
      the coding region between S and all congenic strains possessing the MNS alleles,
      and 2) contractile responses to angiotensin II were significantly and selectively
      reduced in congenic rats harboring the MNS alleles of the SMCN QTL compared with
      S rats. The current investigation presents the first line of evidence that a QTL
      for aortic SMCN exists, and it acts independently of QTLs for BP. The relevant
      congenic strains developed therein potentially provide novel mammalian models for
      the studies of vascular remodeling disorders.

PMID- 15741508
TI  - Computational analysis of 3'-ends of ESTs shows four classes of alternative
      polyadenylation in human, mouse, and rat.
AB  - Alternative initiation, splicing, and polyadenylation are key mechanisms used by
      many organisms to generate diversity among mature mRNA transcripts originating
      from the same transcription unit. While previous computational analyses of
      alternative polyadenylation have focused on polyadenylation activities within or
      downstream of the normal 3'-terminal exons, we present the results of the first
      genome-wide analysis of patterns of alternative polyadenylation in the human,
      mouse, and rat genomes occurring over the entire transcribed regions of mRNAs
      using 3'-ESTs with poly(A) tails aligned to genomic sequences. Four distinct
      classes of patterns of alternative polyadenylation result from this analysis:
      tandem poly(A) sites, composite exons, hidden exons, and truncated exons. We
      estimate that at least 49% (human), 31% (mouse), and 28% (rat) of polyadenylated
      transcription units have alternative polyadenylation. A portion of these
      alternative polyadenylation events result in new protein isoforms.

PMID- 15741509
TI  - Protein structure and evolutionary history determine sequence space topology.
AB  - Understanding the observed variability in the number of homologs of a gene is a
      very important unsolved problem that has broad implications for research into
      coevolution of structure and function, gene duplication, pseudogene formation,
      and possibly for emerging diseases. Here, we attempt to define and elucidate some
      possible causes behind the observed irregularity in sequence space. We present
      evidence that sequence variability and functional diversity of a gene or fold
      family is influenced by quantifiable characteristics of the protein structure.
      These characteristics reflect the structural potential for sequence plasticity,
      i.e., the ability to accept mutation without losing thermodynamic stability. We
      identify a structural feature of a protein domain-contact density-that serves as
      a determinant of entropy in sequence space, i.e., the ability of a protein to
      accept mutations without destroying the fold (also known as fold designability).
      We show that (log) of average gene family size exhibits statistical correlation
      (R(2) > 0.9.) with contact density of its three-dimensional structure. We present
      evidence that the size of individual gene families are influenced not only by the
      designability of the structure, but also by evolutionary history, e.g., the
      amount of time the gene family was in existence. We further show that our
      observed statistical correlation between gene family size and contact density of
      the structure is valid on many levels of evolutionary divergence, i.e., not only
      for closely related sequence, but also for less-related fold and superfamily
      levels of homology.

PMID- 15741510
TI  - Prokaryotic phylogenies inferred from protein structural domains.
AB  - The determination of the phylogenetic relationships among microorganisms has long
      relied primarily on gene sequence information. Given that prokaryotic organisms
      often lack morphological characteristics amenable to phylogenetic analysis,
      prokaryotic phylogenies, in particular, are often based on sequence data. In this
      work, we explore a new source of phylogenetic information, the distribution of
      protein structural domains within fully sequenced prokaryotic genomes. The
      evolution of the structural domains we use has been studied extensively, allowing
      us to base our phylogenetic methods on testable theoretical models of structural
      evolution. We find that the methods that produce reasonable phylogenetic
      relationships are indeed the methods that are most consistent with theoretical
      evolutionary models. This work represents, to our knowledge, the first such
      theoretically motivated phylogeny, as well as the first application of structural
      information to phylogeny on this scale. Our results have strong implications for
      the phylogenetic relationships among prokaryotic organisms and for the
      understanding of protein evolution as a whole.

PMID- 15741511
TI  - From genome to "venome": molecular origin and evolution of the snake venom
      proteome inferred from phylogenetic analysis of toxin sequences and related body
      proteins.
AB  - This study analyzed the origin and evolution of snake venom proteome by means of
      phylogenetic analysis of the amino acid sequences of the toxins and related
      nonvenom proteins. The snake toxins were shown to have arisen from recruitment
      events of genes from within the following protein families: acetylcholinesterase,
      ADAM (disintegrin/metalloproteinase), AVIT, complement C3, crotasin/beta
      defensin, cystatin, endothelin, factor V, factor X, kallikrein, kunitz-type
      proteinase inhibitor, LYNX/SLUR, L-amino oxidase, lectin, natriuretic peptide,
      betanerve growth factor, phospholipase A(2), SPla/Ryanodine, vascular endothelial
      growth factor, and whey acidic protein/secretory leukoproteinase inhibitor. Toxin
      recruitment events were found to have occurred at least 24 times in the evolution
      of snake venom. Two of these toxin derivations (CRISP and kallikrein toxins)
      appear to have been actually the result of modifications of existing salivary
      proteins rather than gene recruitment events. One snake toxin type, the waglerin
      peptides from Tropidolaemus wagleri (Wagler's Viper), did not have a match with
      known proteins and may be derived from a uniquely reptilian peptide. All of the
      snake toxin types still possess the bioactivity of the ancestral proteins in at
      least some of the toxin isoforms. However, this study revealed that the toxin
      types, where the ancestral protein was extensively cysteine cross-linked, were
      the ones that flourished into functionally diverse, novel toxin multigene
      families.

PMID- 15741512
TI  - Post-entrapment genome engineering: first exon size does not affect the
      expression of fusion transcripts generated by gene entrapment.
AB  - Gene trap mutagenesis in mouse embryonic stem cells has been widely used for
      genome-wide studies of mammalian gene function. However, while large numbers of
      genes can be disrupted, individual mutations may suffer from limitations due to
      the structure and/or placement of targeting vector. To extend the utility of gene
      trap mutagenesis, replaceable 3' [or poly(A)] gene trap vectors were developed
      that permit sequences inserted in individual entrapment clones to be engineered
      by Cre-mediated recombination. 3' traps incorporating different drug resistance
      genes could be readily exchanged, simply by selecting for the drug-resistance
      gene of the replacement vector. By substituting different 3' traps, we show that
      otherwise identical fusion genes containing a large first exon (804 nt) are not
      expressed at appreciably lower levels than genes expressing small first exons
      (384 and 151 nt). Thus, size appears to have less effect on the expression and
      processing of first exons than has been reported for internal exons. Finally, a
      retroviral poly(A) trap (consisting of a RNA polymerase II promoter, a neomycin
      resistance gene, and 5'-splice site) typically produced mutagenized clones in
      which vector sequences spliced to the 3'-terminal exons of cellular transcription
      units, suggesting strong selection for fusion transcripts that evade nonsense
      mediated decay. The efficient exchange of poly(A) traps should greatly extend the
      utility of mutant libraries generated by gene entrapment and provides new
      strategies to study the rules that govern the expression of exons inserted
      throughout the genome.

PMID- 15741513
TI  - novoSNP, a novel computational tool for sequence variation discovery.
AB  - Technological improvements shifted sequencing from low-throughput, work
      intensive, gel-based systems to high-throughput capillary systems. This resulted
      in a broad use of genomic resequencing to identify sequence variations in genes
      and regulatory, as well as extended genomic regions. We describe a software
      package, novoSNP, that conscientiously discovers single nucleotide polymorphisms
      (SNPs) and insertion-deletion polymorphisms (INDELs) in sequence trace files in a
      fast, reliable, and user-friendly way. We compared the performance of novoSNP
      with that of PolyPhred and PolyBayes on two data sets. The first data set
      comprised 1028 sequence trace files obtained from diagnostic mutation analyses of
      SCN1A (neuronal voltage-gated sodium channel alpha-subunit type I gene). The
      second data set comprised 9062 sequence trace files from a genomic resequencing
      project aiming at the construction of a high-density SNP map of MAPT (microtubule
      associated protein tau gene). Visual inspection of these data sets had identified
      38 sequence variations for SCN1A and 488 for MAPT. novoSNP automatically
      identified all 38 SCN1A variations including five INDELs, while for MAPT only 15
      of the 488 variations were not correctly marked. PolyPhred detected far fewer
      SNPs as compared to novoSNP and missed nearly all INDELs. PolyBayes, designed for
      the sequence analysis of cloned templates, detected only a limited number of the
      variations present in the data set. Besides the significant improvement in the
      automated detection of sequence variations both in diagnostic mutation analyses
      and in SNP discovery projects, novoSNP also offers a user-friendly interface for
      inspecting possible genetic variations.

PMID- 15741514
TI  - Database of mRNA gene expression profiles of multiple human organs.
AB  - Genome-wide expression profiling of normal tissue may facilitate our
      understanding of the etiology of diseased organs and augment the development of
      new targeted therapeutics. Here, we have developed a high-density gene expression
      database of 18,927 unique genes for 158 normal human samples from 19 different
      organs of 30 different individuals using DNA microarrays. We report four main
      findings. First, despite very diverse sample parameters (e.g., age, ethnicity,
      sex, and postmortem interval), the expression profiles belonging to the same
      organs cluster together, demonstrating internal stability of the database.
      Second, the gene expression profiles reflect major organ-specific functions on
      the molecular level, indicating consistency of our database with known biology.
      Third, we demonstrate that any small (i.e., n approximately 100), randomly
      selected subset of genes can approximately reproduce the hierarchical clustering
      of the full data set, suggesting that the observed differential expression of
      >90% of the probed genes is of biological origin. Fourth, we demonstrate a
      potential application of this database to cancer research by identifying 19 tumor
      specific genes in neuroblastoma. The selected genes are relatively underexpressed
      in all of the organs examined and belong to therapeutically relevant pathways,
      making them potential novel diagnostic markers and targets for therapy. We expect
      this database will be of utility for developing rationally designed molecularly
      targeted therapeutics in diseases such as cancer, as well as for exploring the
      functions of genes.

PMID- 15741515
TI  - The cover. Transients.

PMID- 15741516
TI  - Researchers coax human stem cells to become motor neurons.

PMID- 15741517
TI  - Experimental therapies hold promise for treating amyotrophic lateral sclerosis.

PMID- 15741518
TI  - Genetic variant boosts fertility: inverted region of DNA gives reproductive edge.

PMID- 15741519
TI  - Antiangiogenic therapy a two-trick pony?

PMID- 15741523
TI  - Shared medical decision making.

PMID- 15741524
TI  - Shared medical decision making.

PMID- 15741525
TI  - Subclinical thyroid disease and cardiovascular disease.

PMID- 15741526
TI  - Medical vs surgical management of left main coronary artery disease.

PMID- 15741527
TI  - Obesity in the National Football League.

PMID- 15741528
TI  - Distal microcirculatory protection during percutaneous coronary intervention in
      acute ST-segment elevation myocardial infarction: a randomized controlled trial.
AB  - CONTEXT: Atheromatous and thrombotic embolization during percutaneous coronary
      intervention (PCI) in acute myocardial infarction is common and may result in
      microcirculatory dysfunction, the prevention of which may improve reperfusion
      success, reduce infarct size, and enhance event-free survival. OBJECTIVE: To
      determine whether protection of the distal microcirculation from thromboembolic
      debris liberated during primary PCI results in improved reperfusion and decreased
      infarct size. DESIGN, SETTING, AND PATIENTS: Prospective randomized controlled
      trial at 38 academic and community-based institutions in 7 countries enrolling
      501 patients aged 18 years or older with ST-segment elevation myocardial
      infarction (STEMI) presenting within 6 hours of symptom onset and undergoing
      primary PCI or rescue intervention after failed thrombolysis. INTERVENTIONS:
      Patients were randomized between May 20, 2002, and November 21, 2003, to receive
      PCI with a balloon occlusion and aspiration distal microcirculatory protection
      system vs angioplasty without distal protection. MAIN OUTCOME MEASURES: Coprimary
      end points were ST-segment resolution (STR) measured 30 minutes after PCI by
      continuous Holter monitoring and infarct size measured by technetium Tc 99m
      sestamibi imaging between days 5 and 14. Secondary end points included major
      adverse cardiac events. RESULTS: Among 252 patients assigned to distal
      protection, aspiration was performed in 97% (242/251), all angioplasty balloon
      inflations were fully protected in 79% (193/245), and visible debris was
      retrieved from 73% (182/250). Complete STR was achieved in a similar proportion
      reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239],
      respectively; absolute difference, 1.4% [95% confidence interval, -7.7% to 10.5%;
      P = .78]), and left ventricular infarct size was similar in both groups (median,
      12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac
      events at 6 months occurred with similar frequency in the distal protection and
      control groups (10.0% vs 11.0%, respectively; P = .66). CONCLUSIONS: A distal
      balloon occlusion and aspiration system effectively retrieves embolic debris in
      most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal
      embolic protection did not result in improved microvascular flow, greater
      reperfusion success, reduced infarct size, or enhanced event-free survival.

PMID- 15741529
TI  - Adjuvant chemotherapy in older and younger women with lymph node-positive breast
      cancer.
AB  - CONTEXT: Adjuvant chemotherapy improves survival for patients with local-regional
      breast cancer, but healthy older patients at high risk of recurrence are
      frequently not offered adjuvant chemotherapy, and the benefit of adjuvant
      chemotherapy in older patients is uncertain. OBJECTIVE: To compare the benefits
      and toxic effects of adjuvant chemotherapy among breast cancer patients in age
      groups of 50 years or younger, 51 to 64 years, and 65 years or older. DESIGN AND
      SETTING: Retrospective review of data from 4 randomized trials that accrued
      patients from academic and community medical centers between 1975 and 1999.
      Median follow-up for all patients was 9.6 years. All trials randomized patients
      to different regimens, doses, schedules, and durations of chemotherapy and all
      had a treatment arm with doses or schedules that were regarded to be "high" and
      potentially more toxic. PATIENTS: A total of 6487 women with lymph node-positive
      breast cancer; 542 (8%) patients were 65 years or older and 159 (2%) were 70
      years or older. MAIN OUTCOME MEASURE: Comparison of disease-free survival,
      overall survival, and treatment-related mortality among different age groups.
      RESULTS: Multivariate analysis showed that smaller tumor size, fewer positive
      lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001)
      related to longer disease-free and overall survival. There was no association
      between age and disease-free survival. Overall survival was significantly
      (P<.001) worse for patients aged 65 or older because of death from causes other
      than breast cancer. Thirty-three deaths (0.5% of all patients) were attributed to
      treatment, and older women had higher treatment-related mortality. Older women
      and younger women derived similar reductions in breast cancer mortality and
      recurrence from regimens containing more chemotherapy. CONCLUSION: Age alone
      should not be a contraindication to the use of optimal chemotherapy regimens in
      older women who are in good general health.

PMID- 15741530
TI  - Effect of folate and mecobalamin on hip fractures in patients with stroke: a
      randomized controlled trial.
AB  - CONTEXT: Stroke increases the risk of subsequent hip fracture by 2 to 4 times.
      Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic
      fractures in elderly men and women. Treatment with folate and mecobalamin
      (vitamin B12) may improve hyperhomocysteinemia. OBJECTIVE: To investigate whether
      treatment with folate and vitamin B12 reduces the incidence of hip fractures in
      patients with hemiplegia following stroke. DESIGN, SETTING, AND PATIENTS: A
      double-blind, randomized controlled study of 628 consecutive patients aged 65
      years or older with residual hemiplegia at least 1 year following first ischemic
      stroke, who were recruited from a single Japanese hospital from April 1, 2000, to
      May 31, 2001. Patients were assigned to daily oral treatment with 5 mg of folate
      and 1500 microg of mecobalamin, or double placebo; 559 completed the 2-year
      follow-up. MAIN OUTCOME MEASURE: Incidence of hip fractures in the 2 patient
      groups during the 2-year follow-up. RESULTS: At baseline, patients in both groups
      had high levels of plasma homocysteine and low levels of serum cobalamin and
      serum folate. After 2 years, plasma homocysteine levels decreased by 38% in the
      treatment group and increased by 31% in the placebo group (P<.001). The number of
      hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo
      groups, respectively (P<.001). The adjusted relative risk, absolute risk
      reduction, and the number needed to treat for hip fractures in the treatment vs
      placebo groups were 0.20 (95% confidence interval [CI], 0.08-0.50), 7.1% (95% CI,
      3.6%-10.8%), and 14 (95% CI, 9-28), respectively. No significant adverse effects
      were reported. CONCLUSION: In this Japanese population with a high baseline
      fracture risk, combined treatment with folate and vitamin B12 is safe and
      effective in reducing the risk of a hip fracture in elderly patients following
      stroke.

PMID- 15741532
TI  - Clinical empathy as emotional labor in the patient-physician relationship.
AB  - Empathy should characterize all health care professions. Despite advancement in
      medical technology, the healing relationship between physicians and patients
      remains essential to quality care. We propose that physicians consider empathy as
      emotional labor (ie, management of experienced and displayed emotions to present
      a certain image). Since the publication of Hochschild's The Managed Heart in
      1983, researchers in management and organization behavior have been studying
      emotional labor by service workers, such as flight attendants and bill
      collectors. In this article, we focus on physicians as professionals who are
      expected to be empathic caregivers. They engage in such emotional labor through
      deep acting (ie, generating empathy-consistent emotional and cognitive reactions
      before and during empathic interactions with the patient, similar to the method
      acting tradition used by some stage and screen actors), surface acting (ie,
      forging empathic behaviors toward the patient, absent of consistent emotional and
      cognitive reactions), or both. Although deep acting is preferred, physicians may
      rely on surface acting when immediate emotional and cognitive understanding of
      patients is impossible. Overall, we contend that physicians are more effective
      healers--and enjoy more professional satisfaction--when they engage in the
      process of empathy. We urge physicians first to recognize that their work has an
      element of emotional labor and, second, to consciously practice deep and surface
      acting to empathize with their patients. Medical students and residents can
      benefit from long-term regular training that includes conscious efforts to
      develop their empathic abilities. This will be valuable for both physicians and
      patients facing the increasingly fragmented and technological world of modern
      medicine.

PMID- 15741531
TI  - Impact of participant and physician intervention preferences on randomized
      trials: a systematic review.
AB  - CONTEXT: Allocation on the basis of randomization rather than patient choice is
      the gold standard of unbiased estimates of efficacy in clinical medicine.
      However, randomly allocating patients to treatments that do not accord with their
      preferences may influence internal and external validity. OBJECTIVE: To determine
      whether preferences affect recruitment to trials (external validity) and outcomes
      in trials (internal validity). DATA SOURCES: We searched MEDLINE, EMBASE,
      PsycINFO, CINAHL, AMED, and the Cochrane Library for articles published between
      1966 and September 2004. We also hand-searched several major medical journals,
      searched reference lists of relevant articles, and contacted authors of published
      preference designs. The 2 themes in the first filter of the search strategy were
      preferences and possible determinants of preferences. STUDY SELECTION:
      Comprehensive cohorts and 2-stage trials that measured or recorded patient or
      physician preference, included allocation of participants to random and
      preference cohorts, and followed up all participants. We excluded trials with no
      recording of preference; of decision aids; with measurements of preferences for
      economic analyses; in which patients who refused randomization were followed up
      without reference to preferences; and of nonclinical populations. DATA
      EXTRACTION: Up to 4 reviewers independently evaluated the articles, and
      disagreements were resolved at project steering group meetings. We extracted data
      on study design, measurement of preference, recruitment, attrition, and summary
      data on the primary outcome(s) at baseline and each follow-up point. DATA
      SYNTHESIS: Of 10,023 citations identified, 170 articles met screening criteria
      and 32 (27 comprehensive cohorts and 5 two-stage trials) were determined to be
      eligible and were used in the final review. Although treatment preferences led to
      a substantial proportion of people refusing randomization, there was less
      evidence of bias in the characteristics of individuals agreeing to be randomized.
      Differences in outcome across the trials between randomized and preference groups
      were generally small, particularly in large trials and after accounting for
      baseline measures of outcome. Therefore, there was little evidence that
      preferences substantially interfere with the internal validity of randomized
      trials. CONCLUSIONS: Preferences influence whether people participate in
      randomized trials, but there is little evidence that they significantly affect
      validity.

PMID- 15741533
TI  - A 44-year-old woman with kidney stones.

PMID- 15741534
TI  - A 73-year-old man with hearing loss, 1 year later.

PMID- 15741535
TI  - Distal embolic protection in patients with acute myocardial infarction:
      attractive concept but no evidence of benefit.

PMID- 15741536
TI  - Adjuvant therapy of breast cancer in the elderly: does one size fit all?

PMID- 15741537
TI  - Homocysteine and fracture prevention.

PMID- 15741540
TI  - JAMA patient page. Kidney stones.

PMID- 15741541
TI  - Swapping molecules during cell-cell interactions.
AB  - Interactions between cells of the immune system can lead to intercellular
      exchange of cell-surface molecules. Recent studies indicate that such exchange
      can be bidirectional when natural killer cells interact with their target cells.
      Sprent reviews the mechanisms involved in cell-cell molecular transfer and the
      receptor-ligand interactions involved.

PMID- 15741542
TI  - Teaching resources. Protein phosphatases.
AB  - This Teaching Resource provides lecture notes and slides for a class covering the
      structure and function of protein phosphatases and is part of the course "Cell
      Signaling Systems: A Course for Graduate Students." The lecture begins with a
      discussion of the importance of phosphatases in physiology, recognized by the
      award of a Nobel Prize in 1992, and then proceeds to describe the two types of
      protein phosphatases: serine/threonine and tyrosine phosphatases. The information
      covered includes the structure, regulation, and substrate specificity of protein
      phosphatases, with an emphasis on their importance in disease and clinical
      settings.

PMID- 15741543
TI  - Schistosoma japonicum and occult blood loss in endemic villages in Leyte, the
      Philippines.
AB  - Schistosoma japonicum has been related to anemia, but the mechanisms mediating
      this relationship remain unresolved. The primary objective of this study was to
      assess the role of occult blood loss in mediating S. japonicum-associated anemia
      after adjusting for age, sex, socioeconomic status (SES), and other helminth
      infections. The secondary objective was to identify intensity categories of risk
      for occult blood loss for Trichuris and hookworm after adjustment for the
      presence of other helminth infections. The role of occult blood loss in mediating
      S. japonicum-associated anemia was studied cross-sectionally in 729 individuals 8
      30 years old in Leyte, The Philippines. Three stool specimens were examined in
      duplicate for helminth eggs. Hemoglobin, fecal occult blood loss, and anemia were
      measured and related to the presence and intensity of helminths. Multivariate
      models were made to adjust for confounding by other helminths and SES. In
      multivariate models, hemoglobin significantly decreased with increasing infection
      intensity of S. japonicum, hookworm, and T. trichuria (P < 0.0031, P < 0.0001,
      and P < 0.0001, respectively). Individuals with higher intensities S. japonicum
      and T. trichuria were significantly more likely to be fecal occult positive (odds
      ratio [OR] = 3.54; P = 0.008 and OR = 2.68; P = 0.013, respectively), although
      this was not true for individuals with hookworm. Additionally, individuals with
      higher intensities of S. japonicum, hookworm, and T. trichuria were all more
      likely to be anemic (OR = 3.7, P = 0.0002; OR = 5.3, P = 0.0003; and OR = 1.6, P
      = 0.021, respectively). It is likely that occult blood loss plays a role only at
      heavier intensity S. japonicum infections and some other mechanism, such as
      anemia of inflammation, may be contributing to anemia.

PMID- 15741544
TI  - Efficacy of mirazid in comparison with praziquantel in Egyptian Schistosoma
      mansoni-infected school children and households.
AB  - This trial investigated the anti-schistosomal activity of mirazid in comparison
      with that of praziquantel in Schistosoma mansoni-infected Egyptian patients. The
      sample population was composed of 1,131 individuals (459 school children and 672
      household members). Screening for S. mansoni was conducted using the standard
      Kato Katz technique. Four slides from a single stool sample were examined before
      treatment, and four slides per sample from stool samples obtained on three
      consecutive days were examined post-treatment. All positive eligible subjects
      were randomly assigned into two groups, the first received mirazid at a dose of
      300 mg/day for three consecutive days, and the second received praziquantel at a
      single dose of 40 mg/kg. All treated subjects were examined 4-6 weeks post
      treatment. Mirazid showed low cure rates of 9.1% and 8.9% in S. mansoni-infected
      school children and household members, respectively, compared with cure rates of
      62.5% and 79.7%, respectively, in those treated with praziquantel. Therefore, we
      do not recommend mirazid as an agent to control schistosomiasis.

PMID- 15741545
TI  - Atypical clinical presentation of strongyloidiasis in a patient co-infected with
      human T cell lymphotrophic virus type I.
AB  - Alterations in the immunologic response induced by human T cell lymphotrophic
      virus type I (HTLV-I) predispose the development of disseminated
      strongyloidiasis. We report a case of an atypical clinical presentation of
      strongyloidiasis in a patient co-infected with HTLV-I causing scrotal and
      perineal pain and infertility. Strongyloides stercoralis was found in the
      analysis of the sperm and specific therapy for strongyloidiasis was associated
      with disappearance of the symptoms.

PMID- 15741546
TI  - A recombinant cysteine proteinase from Leishmania (Leishmania) chagasi suitable
      for serodiagnosis of American visceral leishmaniasis.
AB  - A recombinant protein, rLdccys1, which was produced by expression of the gene
      encoding a 30 kDa cysteine proteinase from Leishmania (Leishmania) chagasi, was
      used for detection of antibodies in sera from patients with active visceral
      leishmaniasis (VL) in enzyme-linked immunosorbent assays. Analysis of the
      predicted amino acid sequence of rLdccys1 showed that it contains all the
      characteristics of a cysteine proteinase. The ability of the protein to react
      with sera from humans with VL was also shown by Western blotting. The sensitivity
      for detection of specific antibodies to L. (L.) chagasi bodies using rLdccys1, L.
      (L.) chagasi promastigote lysates, and amastigote lysates was 80%, 98%, and 99%,
      respectively. No cross-reactivity between rLdccys1 and Chagas disease was
      observed, and there was little positive reactivity with sera from patients with
      cutaneous leishmaniasis and tuberculosis, compared with promastigote and
      amastigote extracts. Our findings indicate that rLdccys1 from L. (L.) chagasi
      constitutes a potential tool for the diagnosis of American VL.

PMID- 15741547
TI  - Comparison of meglumine antimoniate and pentamidine for peruvian cutaneous
      leishmaniasis.
AB  - Pentamidine was compared with meglumine antimoniate (Glucantime) for 80 patients
      with cutaneous leishmaniasis due to Leishmania braziliensis in Peru. Of the 40
      patients administered Glucantime (20 mg of antimony [Sb]/kg/day intravenously for
      20 days), 31 cured (78%), 6 failed (15%), of which 5 were due to relapse, and 3
      were lost to follow-up (7%). Of the 40 patients administered pentamidine (2 mg/kg
      every other day for seven injections), 14 were cured (35%), 23 failed (58%), and
      3 were lost to follow-up (7%). Five pentamidine failures were due to relapse, and
      14 failures were due to the presence of parasites two weeks after therapy. Both
      regimens were well tolerated. Gastrointestinal, musculoskeletal, and total
      adverse events were not statistically different in either group. Elevations in
      levels of liver enzymes and pancreatic enzymes were statistically higher in the
      Glucantime group, but no patient terminated therapy prematurely. In this study,
      Glucantime was more effective than pentamidine for treatment of L. braziliensis
      cutaneous leishmaniasis in Peru based on parasitologic as well as clinical
      criteria.

PMID- 15741548
TI  - Short report: surveillance of Leishmania sp. among sand flies in Sicily (Italy)
      using a fluorogenic real-time polymerase chain reaction.
AB  - Leishmaniasis caused by Leishmania infantum is a complex zoonotic disease,
      resulting in cutaneous and visceral manifestations in both dogs and humans. The
      present study involved a published Taqman fluorogenic real-time polymerase chain
      reaction (PCR) assay for surveillance of Leishmania sp. parasites among sand
      flies trapped in two provinces in Sicily, Catania and Agrigento, during the
      summer and fall of 2003. Only male specimens were identified to species level,
      while females were used to evaluate Leishmania sp. infection by PCR testing. The
      two most prevalent sand fly species found were Phlebotomus perfiliewi and P.
      perniciosus. Of the female sand flies tested, 2.9% were positive for Leishmania
      sp. DNA by the PCR.

PMID- 15741549
TI  - Short report: neonatal screening pilot study of Toxoplasma gondii congenital
      infection in Mexico.
AB  - Congenital toxoplasmosis is an obstetric problem in Mexico, but its actual
      frequency is unknown. Using a network for screening of non-infectious disorders,
      we performed a pilot study to determine the frequency of IgM antibodies to
      Toxoplasma gondii in 1,003 infants (53.1% male, mean +/- SD age = 18.3 +/- 13.0
      days, birth weight = 3.116 +/- 0.453 kg) in Mexico City from March to April 2003.
      Blood samples embedded in filter paper were assayed for IgM antibodies using a
      capture enzyme-linked immunosorbent assay and results were confirmed by Western
      blot. Two asymptomatic newborns, one of them premature, had IgM and IgG
      antibodies in a serum sample taken from both the infant and the mother and were
      clinically followed. Our data suggest a frequency of approximately two cases of
      congenital T. gondii infection per 1,000 newborns in Mexico City.

PMID- 15741550
TI  - Seasonal variation of tungiasis in an endemic community.
AB  - Tungiasis (caused by the sand flea Tunga penetrans) is hyperendemic in many
      resource-poor communities in Brazil. To understand transmission dynamics of this
      parasitic skin disease in a typical endemic area, a longitudinal study was
      carried out in a slum in Fortaleza in northeastern Brazil. In a door-to-door
      survey, the population of a randomly selected area (n = 1,460) was examined on
      four occasions for the presence of embedded sand fleas. Prevalence rates were
      33.6% in March (rainy season), 23.8% in June (end of the rainy season), 54.4% in
      September (peak of the dry season), and 16.8% in January (begin of the rainy
      season). Tungiasis was more common in males than in females. The intensity of
      infestation was correlated with the prevalence. The study shows that prevalence
      of tungiasis and parasite burden vary significantly during the year with a peak
      in the dry season. These findings have important consequences for the design of
      control measures.

PMID- 15741551
TI  - The use of the multi-organ-dysfunction score to discriminate different levels of
      severity in severe and complicated Plasmodium falciparum malaria.
AB  - Clinical presentation of Plasmodium falciparum malaria reflects a continuum from
      asymptomatic to multi-organ manifestation and death. Severe malaria is defined by
      the World Health Organization as a qualitative variable. We used the multi-organ
      dysfunction score (MODS) as a quantitative approach for severity in 29 patients
      with severe and complicated P. falciparum malaria to test its usefulness in
      discriminating different severity levels. The MODS on admission was highly
      correlated with the duration of symptoms after admission (r = 0.73, P < 0.001)
      and the serum level of tumor necrosis factor alpha (r = 0.41, P = 0.03). In
      addition, the simplified MODS, based mainly on clinical findings, was also
      correlated with liver and renal dysfunction during hospitalization (alanine
      transaminase, r = 0.42, P = 0.02; blood urea nitrogen, r = 0.45, P = 0.015). A
      score >or= 16 was associated with significantly longer disease duration (P =
      0.018). Thus, this score might provide a predictive value for morbidity in P.
      falciparum malaria.

PMID- 15741552
TI  - A simple, high-throughput method to detect Plasmodium falciparum single
      nucleotide polymorphisms in the dihydrofolate reductase, dihydropteroate
      synthase, and P. falciparum chloroquine resistance transporter genes using
      polymerase chain reaction- and enzyme-linked immunosorbent assay-based
      technology.
AB  - Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum dihydrofolate
      reductase (dhfr), and dihydropteroate synthetase (dhps), and chloroquine
      resistance transporter (Pfcrt) genes are used as molecular markers of P.
      falciparum resistance to sulfadoxine/pyrimethamine and chloroquine. However, to
      be a practical tool in the surveillance of drug resistance, simpler methods for
      high-throughput haplotyping are warranted. Here we describe a quick and simple
      technique that detects dhfr, dhps, and Pfcrt SNPs using polymerase chain reaction
      (PCR)- and enzyme-linked immunosorbent assay (ELISA)-based technology.
      Biotinylated PCR products of dhfr, dhps, or Pfcrt were captured on streptavidin
      coated microtiter plates and sequence-specific oligonucleotide probes (SSOPs)
      were hybridized with the PCR products. A stringent washing procedure enabled
      detection of remaining bound SSOPs and distinguished between the SNPs of dhfr,
      dhps, and Pfcrt with high specificity. The SSOP-ELISA compared well with a
      standard PCR-restriction fragment length polymorphism procedure, and gave
      identical positive results in more than 90% of the P. falciparum slide-positive
      samples tested. The SSOP-ELISA of all dhfr, dhps, or Pfcrt SNPs on 88 samples can
      be performed in a single day and provides quick and reproducible results. The
      system can potentially be modified to detect SNPs in other genes.

PMID- 15741553
TI  - The search for effective and sustainable treatments for Plasmodium falciparum
      malaria in Africa: a model of the selection of resistance by antifolate drugs and
      their combinations.
AB  - The extensive data on the relationship between parasite genotype and
      susceptibility to antifolate drugs can now be coupled with pharmacokinetic
      information to allow construction of models of the selection and spread of
      antifolate-resistant Plasmodium falciparum. In this report, we have modeled the
      effect on resistance selection processes of combinations of antifolate
      antimalarial drugs with artesunate and with amodiaquine under a variety of
      conditions that can be defined by the user. The model is intended to assist
      policymakers in forecasting the useful therapeutic life (UTL) for a range of
      potential combination treatments. The model is especially designed for use by
      African malaria programs so that the interactions of key variables can be
      explored and appropriate combinations of drugs can be chosen for field testing.
      The model provides some important general conclusions: 1) for optimal extension
      of UTL, combination therapy must be deployed before either constituent drug is
      used as monotherapy; 2) even short periods of monotherapy can severely limit the
      usefulness of subsequent combination therapy; and 3) that adding a second drug to
      rescue an antifolate antimalarial that is overtly failing is an inappropriate and
      ultimately wasteful exercise.

PMID- 15741554
TI  - Molecular epidemiology of Plasmodium falciparum resistance to antimalarial drugs
      in Indonesia.
AB  - The extent of gene polymorphisms associated with resistance to chloroquine and
      sulfadoxine-pyrimethamine was examined in field isolates of Plasmodium falciparum
      from Indonesia. Eight malaria-endemic areas, representing a broad region of the
      western and eastern Indonesian Archipelago were surveyed. Blood from 20-50
      patients was collected at each site, DNA was isolated, and the sequences of four
      different genes (dihydrofolate reductase [dhfr], dihydropteroate synthase [dhps],
      P. falciparum multidrug resistance 1 [pfmdr1], and P. falciparum chloroquine
      resistance transporter [pfcrt]) were analyzed using polymerase chain reaction and
      restriction fragment length polymorphisms to detect polymorphisms previously
      shown to be associated with resistance. This analysis identified polymorphisms in
      dhfr at 108-Asn/Thr, 16-Val, and 59-Arg. Polymorphisms in dhps were found less
      frequently, either 437-Gly alone or paired with 540-Glu. The pfcrt 76-Thr
      polymorphism was fixed in all parasite populations and pfmdr1 86-Tyr
      polymorphisms in all populations except in the most eastern regions. The pfmdr1
      1042-Asp polymorphism occurred less frequently. These findings indicate that
      polymorphisms in genes associated with drug resistance in P. falciparum are found
      across a broad region of Indonesia.

PMID- 15741555
TI  - Analysis of the genetic diversity of the Plasmodium falciparum multidrug
      resistance gene 5' upstream region.
AB  - Recent findings indicating a low level of polymorphism in the Plasmodium
      falciparum genome have led to the hypothesis that existent polymorphisms are
      likely to have functional significance. We tested this hypothesis by developing a
      map of the polymorphism in the P. falciparum multidrug resistance 1 (pfmdr1) gene
      5' upstream region and assaying its correlation with drug resistance in a sample
      of field isolates from Dakar, Senegal. A comparison of six geographically diverse
      laboratory strains showed that the 1.94-kb 5'-untranslated region is highly
      monomorphic, with a total of four unique single nucleotide polymorphisms (SNPs)
      being identified. All of the mutations were localized to a 462-basepair region
      proximal to the transcription start point. Analysis of this region in field
      isolates shows the prevalence of one SNP throughout the entire population of
      parasites, irrespective of drug resistance status. The SNP frequency of the
      pfmdr1 upstream region is lower than that found in the noncoding region of other
      genes.

PMID- 15741556
TI  - Randomized, double-blind, phase III, pivotal field trial of the comparative
      immunogenicity, safety, and tolerability of two yellow fever 17D vaccines
      (Arilvax and YF-VAX) in healthy infants and children in Peru.
AB  - We conducted a randomized, double-blind, phase III yellow fever (YF) vaccine
      trial among 1,107 healthy children in Sullana in northern Peru. The safety and
      efficacy (by measurement of geometric mean neutralizing antibody titer responses)
      were determined for two YF vaccines, ARILVAX (n = 738) and YF-VAX(R) (n = 369).
      Serocon-version rates were higher (94.9%) in ARILVAX than in YF-VAX (90.6%)
      recipients. The two-sided 95% confidence interval (YF-VAX-ARILVAX) was (-12.8% to
      -2.5%), indicating that the higher seroconversion rate for Arilvax was
      significant. Post-vaccination (30-day) mean log(10) neutralization indices were
      found to be similar for both products: 1.32 for ARILVAX and 1.26 for YF-VAX (P =
      0.1404, by analysis of variance). A similar number of subjects in each group
      reported at least one adverse event (AE); 441 (59.8%) for ARILVAX versus 211
      (59.9%) for YF-VAX. Most (591; 96.7%) of these were of a mild nature and resolved
      without treatment. There were no treatment-related serious AEs. This is the first
      randomized, double-blind comparison of two YF vaccines in a pediatric population;
      both vaccines were shown to be highly immunogenic and well-tolerated.

PMID- 15741557
TI  - Short report: observations on the multiple feeding behavior of Culex
      tritaeniorhynchus (Diptera: culicidae), the vector of Japanese encephalitis in
      Kerala in southern India.
AB  - A study was undertaken in villages endemic for Japanese encephalitis (JE) in
      Kerala in southern India during the period 1998-2001 to determine the host
      feeding pattern of Culex tritaeniorhynchus, the major vector of JE in southeast
      Asia. A total of 3,067 blood-engorged Cx. tritaeniorhynchus were tested and 2,553
      (82.2%) of the samples could be identified. Culex tritaeniorhynchus had fed
      mainly (56.6%) on cattle. Pig feeding accounted 6.3% of the total samples. Some
      samples (n = 980, 38.3%) were of serologic mixed origin. Of 980 mixed blood-fed
      mosquitoes, 975 (99.5%) had imbibed blood from two distinct hosts and 5 (0.5%)
      imbibed blood from three distinct hosts. Mixed blood meals were mostly (96.7%)
      from cattle and goats. The epidemiologic implications of multiple feeding of Cx.
      tritaeniorhynchus on dampening (dead-end) hosts such as cattle and goats in the
      transmission of JE virus is discussed.

PMID- 15741558
TI  - Spatial patterns of and risk factors for seropositivity for dengue infection.
AB  - Spatial patterns of and risk factors for seropositivity of dengue infection were
      studied in three sites in northern Thailand. A survey was conducted in 2001 among
      1,750 persons. Potential risk factors for dengue infection were measured by
      questionnaire and IgM antibodies against dengue were detected by an enzyme-linked
      immunosorbent assay. The role of landscape as a risk factor was studied using
      land cover maps and a geographic information system. Logistic regression
      identified risk factors for dengue seropositivity. Spatial patterns of
      seropositive cases were determined by cluster analyses. Six percent of the study
      population was seropositive. Risk factors for dengue seropositivity differed per
      site, demonstrating variation in local infection patterns. In the periurban site,
      seropositivity depended on human behavior and factors related to housing quality
      rather than environmental factors. In both rural sites, older persons had a
      higher risk of seropositivity and persons living in houses surrounded by natural
      and agricultural land covers had a lower risk of seropositivity.

PMID- 15741559
TI  - Dispersal of the dengue vector Aedes aegypti within and between rural
      communities.
AB  - Knowledge of mosquito dispersal is critical for vector-borne disease control and
      prevention strategies and for understanding population structure and pathogen
      dissemination. We determined Aedes aegypti flight range and dispersal patterns
      from 21 mark-release-recapture experiments conducted over 11 years (1991-2002) in
      Puerto Rico and Thailand. Dispersal was compared by release location, sex, age,
      season, and village. For all experiments, the majority of mosquitoes were
      collected from their release house or adjacent house. Inter-village movement was
      detected rarely, with a few mosquitoes moving a maximum of 512 meters from one
      Thai village to the next. Average dispersal distances were similar for males and
      females and females released indoors versus outdoors. The movement of Ae. aegypti
      was not influenced by season or age, but differed by village. Results demonstrate
      that adult Ae. aegypti disperse relatively short distances, suggesting that
      people rather than mosquitoes are the primary mode of dengue virus dissemination
      within and among communities.

PMID- 15741560
TI  - Clinical characteristics and risk factors for concurrent bacteremia in adults
      with dengue hemorrhagic fever.
AB  - To better understand the clinical characteristics of concurrent bacteremia (dual
      infection) in patients with dengue hemorrhagic fever/dengue shock syndrome
      (DHF/DSS) and identify predictive risk factors for dual infection, 100 patients
      with DHF/DSS (7 with a dual infection and 93 with DHF/DSS alone [controls]) were
      enrolled in this study. A patient with DHF/DSS who lacked three or more of the
      five most frequently observed manifestations other than fever in controls or
      showed disturbed consciousness was defined as one with unusual dengue
      manifestations. Patients with a dual infection were older, and tended to have
      prolonged fever, higher frequencies of acute renal failure, gastrointestinal
      bleeding, altered consciousness, unusual dengue manifestations, and DSS. Acute
      renal failure (odds ratio [OR] = 51.45, P = 0.002), and prolonged fever (> 5
      days) (OR = 26.07, P = 0.017) were independent risk factors for dual infection.
      Clinicians should be alert to the potential for concurrent bacteremia when
      treating patients with DHF/DSS who are at risk for dual infection and manage them
      accordingly.

PMID- 15741561
TI  - EGFR gene mutations: a call for global x global views of cancer.

PMID- 15741562
TI  - Offering patients colorectal cancer screening.

PMID- 15741563
TI  - Stat bite: Death rates from heart disease and cancer in people younger than 85.

PMID- 15741564
TI  - Cancer surpasses heart disease as leading cause of death for all but the very
      elderly.

PMID- 15741565
TI  - Trial and error: prognostic gene signature study design altered.

PMID- 15741566
TI  - Multiple gene signatures aim to qualify risk in breast cancer.

PMID- 15741567
TI  - As genetic tests move into the mainstream, challenges await for doctors and
      patients.

PMID- 15741568
TI  - Vascular normalization: study examines how antiangiogenesis therapies work.

PMID- 15741569
TI  - NIH adopts strict conflict-of-interest policies for all employees.

PMID- 15741570
TI  - Clinical and biological features associated with epidermal growth factor receptor
      gene mutations in lung cancers.
AB  - BACKGROUND: Mutations in the tyrosine kinase (TK) domain of the epidermal growth
      factor receptor (EGFR) gene in lung cancers are associated with increased
      sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However,
      the role of such mutations in the pathogenesis of lung cancers is unclear.
      METHODS: We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated
      from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples
      from the same patients and 36 neuroendocrine lung tumors collected from patients
      in Japan, Taiwan, the United States, and Australia and from 243 other epithelial
      cancers. Mutation status was compared with clinicopathologic features and with
      the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is
      also frequently mutated in lung cancers. All statistical tests were two sided.
      RESULTS: We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the
      617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung
      tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were
      statistically significantly more frequent in never smokers than ever smokers (51%
      versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus
      3%), in patients of East Asian ethnicity versus other ethnicities (30% versus
      8%), and in females versus males (42% versus 14%; all P < .001). EGFR TK domain
      mutation status was not associated with patient age at diagnosis, clinical stage,
      the presence of bronchioloalveolar histologic features, or overall survival. The
      EGFR TK domain mutations we detected were of three common types: in-frame
      deletions in exon 19, single missense mutations in exon 21, and in-frame
      duplications/insertions in exon 20. Rare missense mutations were also detected in
      exons 18, 20, and 21. KRAS gene mutations were present in 50 (8%) of the 617
      NSCLCs but not in any tumors with an EGFR TK domain mutation. CONCLUSIONS:
      Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer
      pathogenesis. EGFR TK domain mutations are the first molecular change known to
      occur specifically in never smokers.

PMID- 15741571
TI  - Randomized trial of different screening strategies for colorectal cancer: patient
      response and detection rates.
AB  - BACKGROUND: Although there is general consensus concerning the efficacy of
      colorectal cancer screening, there is a lack of agreement about which routine
      screening strategy should be adopted. We compared the participation and detection
      rates achievable through different strategies of colorectal cancer screening.
      METHODS: From November 1999 through June 2001 we conducted a multicenter,
      randomized trial in Italy among a sample of 55-64 year olds in the general
      population who had an average risk of colorectal cancer. People with previous
      colorectal cancer, adenomas, inflammatory bowel disease, a recent (< or =2 years)
      colorectal endoscopy or fecal occult blood test (FOBT), or two first-degree
      relatives with colorectal cancer were excluded. Eligible subjects were randomly
      assigned, within the roster of their general practitioner, to 1) biennial FOBT
      (delivered by mail), 2) biennial FOBT (delivered by general practitioner or a
      screening facility), 3) patient's choice of FOBT or "once-only" sigmoidoscopy, 4)
      "once-only" sigmoidoscopy, or 5) sigmoidoscopy followed by biennial FOBT. An
      immunologic FOBT was used. Participation and detection rates of the strategies
      tested were compared using multivariable logistic regression models that adjusted
      for age, sex, and screening center. All statistical tests were two-sided.
      RESULTS: Of 28 319 people sampled, 1637 were excluded and 26 682 were randomly
      assigned to a screening arm. After excluding undelivered letters (n = 427), the
      participation rates for groups 1, 2, 3, 4, and 5 were 30.1% (682/2266), 28.1%
      (1654/5893), 27.1% (970/3579), 28.1% (1026/3650), and 28.1% (3049/10 867),
      respectively. Of the 2858 subjects screened by FOBT, 122 (4.3%) had a positive
      test result, 10 (3.5 per 1000) had colorectal cancer, and 39 (1.4%) had an
      advanced adenoma. Among the 4466 subjects screened by sigmoidoscopy, 341 (7.6%)
      were referred for colonoscopy, 18 (4 per 1000) had colorectal cancer, and 229
      (5.1%) harbored an advanced adenoma. CONCLUSIONS: The participation rates were
      similar for sigmoidoscopy and FOBT. The detection rate for advanced neoplasia was
      three times higher following screening by sigmoidoscopy than by FOBT.

PMID- 15741572
TI  - Physician predictors of mammographic accuracy.
AB  - BACKGROUND: The association between physician experience and the accuracy of
      screening mammography in community practice is not well studied. We identified
      characteristics of U.S. physicians associated with the accuracy of screening
      mammography. METHODS: Data were obtained from the Breast Cancer Surveillance
      Consortium and the American Medical Association Master File. Unadjusted
      mammography sensitivity and specificity were calculated according to physician
      characteristics. We modeled mammography sensitivity and specificity by
      multivariable logistic regression as a function of patient and physician
      characteristics. All statistical tests were two-sided. RESULTS: We studied 209
      physicians who interpreted 1,220,046 screening mammograms from January 1, 1995,
      through December 31, 2000, of which 7143 (5.9 per 1000 mammograms) were
      associated with breast cancer within 12 months of screening. Each physician
      interpreted a mean of 6011 screening mammograms (95% confidence interval [CI] =
      4998 to 6677), including a mean of 34 (95% CI = 28 to 40) from women diagnosed
      with breast cancer. The mean sensitivity was 77% (range = 29%-97%), and the mean
      false-positive rate was 10% (range = 1%-29%). After adjustment for the patient
      characteristics of those whose mammograms they interpreted, physician
      characteristics were strongly associated with specificity. Higher specificity was
      associated with at least 25 years (versus less than 10 years) since receipt of a
      medical degree (for physicians practicing for 25-29 years, odds ratio [OR] =
      1.54, 95% CI = 1.14 to 2.08; P = .006), interpretation of 2500-4000 (versus 481
      750) screening mammograms annually (OR = 1.30, 95% CI = 1.06 to 1.59; P = .011)
      and a high focus on screening mammography compared with diagnostic mammography
      (OR = 1.59, 95% CI = 1.37 to 1.82; P<.001). Higher overall accuracy was
      associated with more experience and with a higher focus on screening mammography.
      Compared with physicians who interpret 481-750 mammograms annually and had a low
      screening focus, physicians who interpret 2500-4000 mammograms annually and had a
      high screening focus had approximately 50% fewer false-positive examinations and
      detected a few less cancers. CONCLUSION: Raising the annual volume requirements
      in the Mammography Quality Standards Act might improve the overall quality of
      screening mammography in the United States.

PMID- 15741573
TI  - Are breast density and bone mineral density independent risk factors for breast
      cancer?
AB  - BACKGROUND: Mammographic breast density and bone mineral density (BMD) are
      markers of cumulative exposure to estrogen. Previous studies have suggested that
      women with high mammographic breast density or high BMD are at increased risk of
      breast cancer. We determined whether mammographic breast density and BMD of the
      hip and spine are correlated and independently associated with breast cancer
      risk. METHODS: We conducted a cross-sectional study (N = 15,254) and a nested
      case-control study (of 208 women with breast cancer and 436 control subjects)
      among women aged 28 years or older who had a screening mammography examination
      and hip BMD measurement within 2 years. Breast density for 3105 of the women was
      classified using the American College of Radiology Breast Imaging Reporting and
      Data System (BI-RADS) categories, and percentage mammographic breast density
      among the case patients and control subjects was quantified with a computer-based
      threshold method. Spearman rank partial correlation coefficient and Pearson's
      correlation coefficient were used to examine correlations between BI-RADS breast
      density and BMD and between percentage mammographic breast density and BMD,
      respectively, in women without breast cancer. Logistic regression was used to
      examine the association of breast cancer with percentage mammographic breast
      density and BMD. All statistical tests were two-sided. RESULTS: Neither BI-RADS
      breast density nor percentage breast density was correlated with hip or spine BMD
      (correlation coefficient = -.02 and -.01 for BI-RADS, respectively, and -.06 and
      .01 for percentage breast density, respectively). Neither hip BMD nor spine BMD
      had a statistically significant relationship with breast cancer risk. Women with
      breast density in the highest sextile had an approximately threefold increased
      risk of breast cancer compared with women in the lowest sextile (odds ratio =
      2.7, 95% confidence interval = 1.4 to 5.4); adjusting for hip or spine BMD did
      not change the association between breast density and breast cancer risk.
      CONCLUSION: Breast density is strongly associated with increased risk of breast
      cancer, even after taking into account reproductive and hormonal risk factors,
      whereas BMD, although a possible marker of lifetime exposure to estrogen, is not.
      Thus, a component of breast density that is independent of estrogen-mediated
      effects may contribute to breast cancer risk.

PMID- 15741574
TI  - Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case
      control study.
AB  - BACKGROUND: Tamoxifen treatment of breast cancer is associated with an increased
      risk of endometrial cancer, but tamoxifen-related risks of endometrial cancer are
      unclear in premenopausal women, in long-term users of tamoxifen, and in women for
      whom several years have passed since ending treatment. We conducted a case
      control study in Britain to investigate these risks. METHODS: We compared
      treatment information on 813 case patients who had endometrial cancer after their
      diagnosis for breast cancer and 1067 control patients who had breast cancer but
      not subsequent endometrial cancer. We assessed risk by conditional logistic
      regression analysis. All statistical tests were two-sided. RESULTS: Overall,
      tamoxifen treatment, compared with no treatment, was associated with an increased
      risk of endometrial cancer (odds ratio [OR] = 2.4; 95% confidence interval [CI] =
      1.8 to 3.0). Risk increased statistically significantly (P(trend)<.001) with
      duration of treatment (for > or =5 years of treatment compared with no treatment,
      OR = 3.6, 95% CI = 2.6 to 4.8). As an indication of background levels of
      treatment, 16% of control patients received 5 years or more of treatment. Risk of
      endometrial cancer adjusted for treatment duration did not diminish in follow-up
      to at least 5 years after the last treatment ended. Risk of endometrial cancer
      was not associated with the daily dose of tamoxifen and was comparable in pre-
      and postmenopausal women. Ever treatment with tamoxifen was associated with a
      much greater risk of Mullerian and mesodermal mixed endometrial tumors (OR =
      13.5, 95% CI = 4.1 to 44.5) than of adenocarcinoma (OR = 2.1, 95% CI = 1.6 to
      2.7) or clear cell and papillary serous tumors (OR = 3.1, 95% CI = 0.8 to 17.9).
      CONCLUSIONS: There is an increasing risk of endometrial cancer associated with
      longer tamoxifen treatment, extending well beyond 5 years. The increased risk of
      endometrial cancer associated with tamoxifen treatment should be considered
      clinically for both premenopausal and postmenopausal women during treatment and
      for at least 5 years after the last treatment.

PMID- 15741575
TI  - Contribution of hMTH1 to the maintenance of 8-oxoguanine levels in lung DNA of
      non-small-cell lung cancer patients.
AB  - BACKGROUND: The level of 8-oxoguanine (8-oxoG), a general marker of oxidative DNA
      damage, in DNA is the result of both an equilibrium between the rates of its
      formation and removal from DNA by DNA repair enzymes and the removal of 8-oxodGTP
      from the cellular nucleotide pool by hydrolysis to 8-oxodGMP, preventing its
      incorporation into DNA. To determine the contribution of each component to the
      level of 8-oxoG in DNA, we compared 8-oxoG-excising activity (encoded by hOGG1),
      8-oxodGTPase activity (encoded by hMTH1), and 8-oxoG levels in DNA from tumors
      and surrounding normal lung tissues from non-small-cell lung cancer patients.
      METHODS: We measured the level of 8-oxoG in DNA of 47 patients by high
      performance liquid chromatography/electrochemical detection (HPLC/ECD), hOGG1
      activity in tissue extracts of 56 patients by the nicking assay using an
      oligodeoxynucleotide containing a single 8-oxoG, and hMTH1 activity in tissue
      extracts of 33 patients by HPLC/UV detection. All statistical tests were two
      sided. RESULTS: The 8-oxoG level was lower in tumor DNA than in DNA from normal
      lung tissue (geometric mean: 5.81 versus 10.18 8-oxoG/10(6) G, geometric mean of
      difference = 1.75; P<.001). The hOGG1 activity was also lower in tumor than in
      normal lung tissue (geometric mean: 8.76 versus 20.91 pmol/h/mg protein,
      geometric mean of difference = 2.39; P<.001), whereas the hMTH1 activity was
      higher in tumor than in normal lung tissue (geometric mean: 28.79 versus 8.94
      nmol/h/mg protein, geometric mean of difference = 0.31; P<.001). The activity of
      hMTH1 was three orders of magnitude higher than that of hOGG1 (nanomoles versus
      picomoles per hour per milligram of protein, respectively). CONCLUSIONS: Several
      different components contribute to the maintenance of 8-oxoG levels in human DNA,
      with the greatest contributor being the removal of 8-oxodGTP from the cellular
      nucleotide pool by hMTH1.

PMID- 15741576
TI  - Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk
      in a prospective study.
AB  - The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated a
      32% reduction in prostate cancer incidence in response to daily alpha-tocopherol
      supplementation. We examined baseline serum concentrations of alpha-tocopherol
      and gamma-tocopherol to compare their respective associations with prostate
      cancer risk. From the ATBC Study cohort of 29 133 Finnish men, 50-69 years old,
      we randomly selected 100 incident prostate cancer case patients and matched 200
      control subjects. Odds ratios and 95% confidence intervals (CIs) were estimated
      for the serum tocopherols (measured by high-performance liquid chromatography)
      using logistic regression models. All P values were two-sided. Odds ratios for
      the highest versus the lowest tertiles were 0.49 (95% CI = 0.24 to 1.01, P(trend)
      = .05) for alpha-tocopherol and 0.57 (95% CI = 0.31 to 1.06, P(trend) = .08) for
      gamma-tocopherol. Further analyses indicated that the association of high serum
      tocopherols with low prostate cancer risk was stronger in the alpha-tocopherol
      supplemented group than in those not receiving alpha-tocopherol. Participants
      with higher circulating concentrations of the major vitamin E fractions, alpha
      tocopherol and gamma-tocopherol, had similarly lower prostate cancer risk.

PMID- 15741577
TI  - Re: Reason for late-stage breast cancer: absence of screening or detection, or
      breakdown in follow-up?

PMID- 15741578
TI  - Re: Determinants of BRAF mutations in primary melanomas.

PMID- 15741579
TI  - Physostigmine does not effect arousal but produces toxicity in an animal model of
      severe gamma-hydroxybutyrate intoxication.
AB  - OBJECTIVES: Physostigmine is an acetylcholinesterase inhibitor and can produce
      fasciculations, seizures, bradycardia, and asystole. gamma-hydroxybutyrate (GHB)
      increases acetylcholine levels in the central nervous system and can decrease
      heart rate. Despite this, physostigmine has been proposed as an arousal agent to
      treat coma from overdoses of GHB. The authors hypothesized that in the setting of
      severe GHB intoxication, physostigmine would reverse sedation without producing
      adverse effects such as a decrease in heart rate, seizures, and fasciculations.
      METHODS: GHB intoxication was induced in 20 rats by intraperitoneal injection of
      700 mg/kg of the GHB precursor gamma-butyrolactone. One hour later, rats were
      randomly assigned to receive either physostigmine (0.06 mg/kg) intraperitoneally
      or an equivalent volume of saline. After administration of physostigmine, rats
      were continuously monitored by a blinded observer for arousal (return of righting
      reflex), fasciculations, and seizures. Heart rate and respiratory rate were
      recorded at 0, 5, 15, and 60 minutes after administration of physostigmine. Data
      were analyzed using repeated-measures analysis of variance and chi-square test. A
      pretest sample size calculation determined that 10 rats per group would detect a
      change in arousal from 0% to 50% and a 10% change in heart rate. RESULTS: No rats
      in either group had arousal within one hour (p = 1.0); however, ten of ten
      physostigmine-treated rats developed signs of physostigmine toxicity
      (fasciculations, 7; seizures, 3), while no controls developed signs of
      physostigmine toxicity (p = 0.00). The authors were unable to detect a decrease
      in heart rate. CONCLUSIONS: Physostigmine did not produce a 50% change in arousal
      as measured by a return of righting reflex but did produce physostigmine toxicity
      (fasciculations and seizures) in this rat model of severe GHB intoxication.

PMID- 15741580
TI  - The utility of the bispectral index in procedural sedation with propofol in the
      emergency department.
AB  - The bispectral index (BIS) may be a useful monitor to predict the level of
      awareness in patients undergoing procedural sedation in the emergency department
      (ED). OBJECTIVES: The authors hypothesized that using the BIS during procedural
      sedation in the ED would increase the recognition of adequately sedated patients,
      thus reducing oversedation and the corresponding increased rate of respiratory
      depression (RD). As a result, the occurrence of RD would be reduced. METHODS:
      This was a prospective randomized study of ED procedural sedation with propofol.
      Sedations were randomized to have the treating physician either blinded or not
      blinded to information from the BIS monitor. Vital signs, pulse oximetry, end
      tidal carbon dioxide (ETCO(2)), propofol dosage, and the BIS score were recorded.
      RD was defined as a change in ETCO(2) greater than 10 mm Hg, an oxygen saturation
      of less than 90% at any time, or an absent ETCO(2) waveform. The RD rates were
      compared with chi-square tests. RESULTS: One hundred five patients were enrolled
      in the study; five were excluded due to study protocol violations. No serious
      adverse events were reported. RD was seen in 29 of 100 (29%) patients; 18 of 48
      in the BIS-blinded group and 11 of 52 in the BIS-unblinded group had RD (p =
      0.06). For patients requiring only a single dose of propofol, three of 15 in the
      BIS-blinded group and four of 18 in the BIS-unblinded group met the criteria for
      RD (p = 0.87). For patients requiring multiple doses of propofol, 15 of 33
      patients in the BIS-blinded group and seven of 34 patients in the BIS-unblinded
      group met criteria for RD (p = 0.02). The mean BIS nadir for BIS-blinded patients
      was 60.9 (95% CI = 56.9 to 65.0) and that for BIS-unblinded patients was 63.2
      (95% CI = 57.7 to 65.3) (p = 0.22). CONCLUSIONS: There was a lower rate of RD
      when physicians had access to the BIS during procedural sedations. This
      difference was greater in sedations requiring multiple doses of propofol. There
      was no difference in the rate of RD when only a single dose was given.

PMID- 15741581
TI  - Emergency physician recognition of adverse drug-related events in elder patients
      presenting to an emergency department.
AB  - OBJECTIVES: The authors examined the ability of emergency physicians (EPs) to
      recognize adverse drug-related events (ADREs) in elder patients presenting to the
      emergency department (ED). METHODS: This was a prospective observational study of
      patients at least 65 years of age who presented to the ED. ADREs were identified
      using a validated, standardized scoring system. EP recognition of ADREs was
      assessed through physician interview and subsequent chart review. RESULTS: A
      total of 161 patients were enrolled in the study. Thirty-seven ADREs were
      identified, which occurred in 26 patients (16.2%; 95% confidence interval [CI] =
      10.5% to 22.0%). The treating EPs recognized 51.2% (95% CI = 35.2% to 67.4%) of
      all ADREs. There was better recognition of those ADREs related to the patient's
      chief complaint (91%; 95% CI = 74.1% to 100%) as compared with recognition of
      ADREs that were not associated with the chief complaint (32.1%; 95% CI = 14.8% to
      49%). EPs recognized six of seven severe ADREs (85.7%), 13 of 23 moderate ADREs
      (56.5%; 95% CI = 36.8% to 77%), and none of the mild ADREs. Recognition of ADREs
      varied with medication class. CONCLUSIONS: EP performance was superior at
      identifying severe ADREs relating to the patients' chief complaints. However, EP
      performance was suboptimal with respect to identifying ADREs of lower severity,
      having missed a significant number of ADREs of moderate severity as well as ones
      unrelated to the patients' chief complaints. ADRE detection methods need to be
      developed for the ED to aid EPs in detecting those ADREs that are most likely to
      be missed.

PMID- 15741582
TI  - What characteristics of applicants to emergency medicine residency programs
      predict future success as an emergency medicine resident?
AB  - OBJECTIVES: Program directors of emergency medicine (EM) residencies attempt to
      select candidates who will subsequently perform well as residents. This study was
      undertaken to identify characteristics available at the time of application to an
      EM residency that predict future success in residency. METHODS: The EM faculty at
      the University of California San Diego (UCSD) completed a one-time confidential
      assessment of EM residents on performance in residency at the time of graduation.
      The faculty member compared the graduate with all residents (both EM and non-EM)
      with whom the faculty member had previously worked using the five-point scale: >
      or =90th percentile, 70th-89th percentile, 50th-69th percentile, 30th-49th
      percentile, or < 30th percentile. Descriptive statistics, ordinal logistic
      regression (OLR), classification and regression tree (CART) analysis, and
      multiple additive regression tree (MART) analysis were used to find predictors
      for each of the outcome variables. RESULTS: Fifty-four graduates were evaluated.
      The medical school attended (MSA) was the strongest predictor of overall
      performance in residency in all regression models. OLR showed that MSA and
      "distinctive factors" (being a championship athlete, medical school officer,
      etc.) were significant predictors and may deserve greater weighting in the
      selection process. The most robust MART model demonstrated that MSA, dean's
      letter of recommendation, and distinctive factors had the most impact on overall
      performance in an EM residency. CONCLUSIONS: Using regression modeling, it may be
      possible to predict future resident performance from characteristics contained in
      residency applications. Applicants from top-tier medical schools and those with
      distinctive talents were more successful in the UCSD EM residency.

PMID- 15741583
TI  - Smoking stage of change and interest in an emergency department-based
      intervention.
AB  - OBJECTIVES: To examine factors associated with motivation to quit smoking and
      interest in an emergency department (ED)-based intervention. METHODS: Consecutive
      ED patients 18 years of age and older were interviewed. Severely ill and
      cognitively disabled patients were excluded. Smoking history, stage of change,
      self-efficacy, presence of a smoking-related illness, interest in an ED-based
      smoking intervention, and screening/counseling by the patient's ED provider were
      assessed. RESULTS: A total of 1,461 of 2,314 patients (64%) were interviewed. A
      total of 581 (40%) currently smoked, with 21% in precontemplation (no intention
      to quit), 43% in contemplation (intention to quit but not within the next 30
      days), and 36% in preparation (intention to quit within the next 30 days).
      Approximately 50% indicated a willingness to remain 15 extra minutes in the ED to
      receive counseling. Only 8% received counseling by their ED provider. A
      regression analysis showed that greater readiness to change was associated with
      multiple lifetime quit attempts, presence of a quit attempt in the past 30 days,
      and higher self-efficacy. Interest in an ED-based intervention was more likely
      among patients who reported higher self-efficacy. CONCLUSIONS: Approximately 50%
      of smokers reported at least moderate interest in an ED-based intervention and a
      willingness to stay 15 extra minutes, but only 8% reported receiving counseling
      during their ED visit. Considering time and resource constraints,
      counseling/referral may be best suited for patients characterized by a strong
      desire to quit, multiple previous quit attempts, high self-efficacy, a smoking
      related ED visit, and strong interest in ED-based counseling.

PMID- 15741584
TI  - Evaluation of the Emergency Severity Index (version 3) triage algorithm in
      pediatric patients.
AB  - OBJECTIVES: As demand for emergency services outpaces available allocated
      resources, emergency department (ED) triage systems face increasing scrutiny.
      Longer waits for care make the use of reliable, valid triage systems imperative
      to patient safety. Little is known about the reliability and validity of triage
      systems in children. The purpose of this study was to evaluate the reliability
      and validity of the Emergency Severity Index version 3 (ESIv.3) triage algorithm
      in a pediatric population. METHODS: This two-phase investigation used both
      retrospective chart review and prospective, observational designs. Interrater
      reliability was evaluated using ED triage scenarios, a prospective cohort of ED
      patients presenting to triage, and retrospective triage assignments using the
      original triage note. ED triage nurses, nurse investigators, and physician
      investigators performed retrospective blinded triages using only the original
      triage note to assess reproducibility. In the second phase, validity was assessed
      using a retrospective analysis of observed resource use, ED length of stay, and
      hospitalization compared with resource utilization estimated at triage by the
      ESI. RESULTS: In the reliability phase, weighted kappa for ED nurse triage of
      standard scenarios ranged from 0.84 to 1.00, representing excellent agreement.
      Twenty ED pediatric patients were triaged simultaneously by an ED triage nurse
      and the nurse investigator. Weighted kappa was 0.82 (95% confidence interval =
      0.66 to 0.98), also representing strong agreement between raters. When used for
      retrospective chart review, the weighted kappa statistics ranged from 0.42 to
      0.84, representing poor to good agreement among the different categories of
      reviewers. During the validity phase, 510 patients were included in the final
      data analysis. Hospitalization, ED length of stay, and resource utilization were
      strongly associated with ESIv.3 category. CONCLUSIONS: The ESI triage algorithm
      demonstrated reliability and validity between triage assignment and resource use
      in this group of ED pediatric patients.

PMID- 15741585
TI  - An electronic chart prompt to decrease proprietary antibiotic prescription to
      self-pay patients.
AB  - OBJECTIVES: Emergency physicians unaware of patients' insurance status may
      prescribe expensive proprietary antibiotics for patients who cannot afford them.
      The objective of this study was to develop a clinical decision support system to
      display patient insurance status before prescription writing for outpatient
      conditions. METHODS: This was a 26-week "before-and-after" trial at an urban
      emergency department (ED) with 78,000 visits/year treating a medically
      underserved population. Sixty-one prescribers, including attending physicians,
      residents, and physician assistants, participated. All patients older than 18
      years of age discharged from the ED receiving antibiotic prescriptions were
      eligible. The electronic ED chart is linked to prescription-writing software,
      which includes a menu of 74 antibiotics. The system was programmed so that when
      an emergency physician accessed the prescription menu, a prompt appeared
      displaying insurance status. Prescribers also received educational interventions.
      The main outcome measure was the percentage of prescribers who reduced their
      prescription writing of proprietary antibiotics to self-pay patients. Data were
      analyzed with cluster techniques using SPSS 10.0 (SPSS Inc., Chicago, IL).
      RESULTS: Of 594 prescriptions written for self-pay patients before prompt
      insertion, 158 (26.6%) were for proprietary antibiotics. After the intervention,
      self-pay patients received 564 antibiotic prescriptions, of which 117 (20.7%)
      were for proprietary drugs. Analyzed by prescriber, the reduction in the
      prescription rate for proprietary antibiotics was statistically significant (p =
      0.03, chi(2) test). Patients with respiratory or urinary infections also had a
      statistically significant reduction in proprietary antibiotic prescription (p =
      0.03). CONCLUSIONS: A clinical decision support system, integrated into a
      prescription-writing program, can decrease the prescription of proprietary
      antibiotics for self-pay patients in the ED.

PMID- 15741586
TI  - Factors associated with patients who leave without being seen.
AB  - OBJECTIVES: Patients who leave without being seen (LWBS) can be an indicator of
      patient satisfaction and quality for emergency departments (ED). The objective of
      this study was to develop a model to determine factors associated with patients
      who LWBS. METHODS: A modified case-crossover design to determine the transient
      effects on the risk of acute events was used. Over a four-month period, time
      intervals when patients LWBS were matched (within two weeks), according to time
      of day and day of week, with time periods when patients did not LWBS. Factors
      considered were percentage of ED bed capacity, acuity of ED patients, length of
      stay of discharged patients in the ED, patients awaiting an admission bed in the
      ED, inpatient floor capacity, intensive care unit capacity, and the
      characteristics of the attending physician in charge. McNemar test, Wilcoxon
      signed-rank test, and conditional logistic regression analyses were used to
      determine significant variables. RESULTS: Over the study period, there were
      11,652 visits, of which 213 (1.8%) resulted in patients who LWBS. Measures of
      inpatient capacity were not associated with patients who LWBS and ED capacity was
      only associated when >100%. This association increased with increasing capacity.
      Other significant factors were older age (p < 0.01) and completion of an
      emergency medicine residency (p < 0.01) of the physician in charge. When factors
      were considered in a multivariate model, ED capacity >140% (odds ratio, 1.96; 95%
      confidence interval = 1.22 to 3.17) and noncompletion of an emergency medicine
      residency (odds ratio, 1.85; 95% confidence interval = 1.17 to 2.93) were most
      important. CONCLUSIONS: ED capacity >100% is associated with patients who LWBS
      and is most significant at 140% capacity. ED capacity of 100% may not be a
      sensitive measure for overcrowding. Physician factors, especially emergency
      medicine training, also appear to be important when using LWBS as a quality
      indicator.

PMID- 15741587
TI  - Clinicopathological conference: a 29-year-old man with vomiting and chest pain.

PMID- 15741588
TI  - Brief interventions for problematic behaviors in the emergency department: don't
      overlook "12-step" recovery programs that advocate total abstinence (and don't be
      afraid to delegate the intervention task to a qualified, trained assistant).

PMID- 15741589
TI  - Educational research: time to reach the bar, not lower it.

PMID- 15741590
TI  - Development and implementation of an emergency practitioner-performed brief
      intervention for hazardous and harmful drinkers in the emergency department.
AB  - OBJECTIVES: 1) To develop and teach a brief intervention (BI) for "hazardous and
      harmful" (HH) drinkers in the emergency department (ED); 2) to determine whether
      emergency practitioners (EPs) (faculty, residents, and physician associates) can
      demonstrate proficiency in the intervention; and 3) to determine whether it is
      feasible for EPs to perform the BI during routine clinical care. METHODS: The
      Brief Negotiation Interview (BNI) was developed for a population of HH drinkers.
      EPs working in an urban, teaching hospital were trained during two-hour skills
      based sessions. They were then tested for adherence to and competence with the
      BNI protocol using standardized patient scenarios and a checklist of critical
      components of the BNI. Finally, the EPs performed the BNI as part of routine ED
      clinical care in the context of a randomized controlled trial to test the
      efficacy of BI on patient outcomes. RESULTS: The BNI was developed, modified, and
      finalized in a manual, based on pilot testing. Eleven training sessions with 58
      EPs were conducted from March 2002 to August 2003. Ninety-one percent (53/58) of
      the trained EPs passed the proficiency examination; 96% passed after remediation.
      Two EPs left prior to remediation. Subsequently, 247 BNIs were performed by 47
      EPs. The mean (+/- standard deviation) number of BNIs per EP was 5.28 (+/- 4.91;
      range 0-28). The mean duration of the BNI was 7.75 minutes (+/- 3.18; range 4
      24). CONCLUSIONS: A BNI for HH drinkers can be successfully developed for EPs.
      EPs can demonstrate proficiency in performing the BNI in routine ED clinical
      practice.

PMID- 15741591
TI  - Development of a web-based database to manage American College of Emergency
      Physicians/American Academy of Pediatrics Emergency Information Forms.
AB  - Children with special health care needs require special advanced planning for
      their unique emergencies. A Web site has been developed to allow secure Internet
      access to a database of Emergency Information Forms developed using the American
      College of Emergency Physicians/American Academy of Pediatrics format. The
      content and organization of the Web site, found at http://www.memscis.org, are
      described. A tour of the site is available. A set of XML data elements has been
      defined. Additional disaster preparedness elements have been added to the
      American College of Emergency Physicians/American Academy of Pediatrics Emergency
      Information Forms. The organization, security, and relationship of the site to
      electronic health records are described.

PMID- 15741592
TI  - Who should be estimating a patient's weight in the emergency department?
AB  - OBJECTIVES: Medical personnel often need to estimate a patient's weight rapidly
      and accurately to administer pharmacologic agents whose dosages are based on
      weight. Inaccurate estimates of weight may result in administration of either
      subtherapeutic or, in other cases, toxic doses of medications. The hypothesis of
      this study was that the patient is a more accurate estimator of his or her own
      weight than the physician or nurse caring for him or her. METHODS: This was a
      prospective study in which adult patients presenting to an urban emergency
      department (ED) were examined for study eligibility. Patients unable to stand
      were excluded. The patient, physician, and nurse caring for the patients were
      independently asked to estimate the patients' weights. The patients were then
      weighed. RESULTS: A convenience sample of 458 patients were enrolled during a
      four-week period. The median measured (actual) weight was 172.5 lb. The best
      estimate of a patient's weight was made by the patient himself or herself: the
      median difference between patient estimates and actual weights was 0 lb
      (interquartile range [IQR] = -5 to 5). The physicians and nurses had larger
      underestimates: -5 lb (IQR = -22 to 12) and -6 lb (IQR = -22 to 10),
      respectively. Weight was estimated within 10% of actual weight by 90.6% of the
      patients, 50.4% of the physicians, and 49.6% of the nurses. CONCLUSIONS: When a
      patient is unable to be weighed, the patient's own weight estimate should be
      used. If neither is possible, the physician or nurse should estimate the
      patient's weight.

PMID- 15741593
TI  - The incidence and burden of ladder, structure, and scaffolding falls.
AB  - OBJECTIVES: The national morbidity and mortality associated with falls from a
      height is incompletely described. The authors estimated the rates of injury,
      hospitalization, and mortality due to these falls for subgroups of the U.S.
      population. METHODS: Administrative databases (1995-2000) provided national
      samples of patients treated for injuries following a fall from a height (ICD-9-CM
      E-codes E881.0, E881.1, or E882). Inpatient data are from the Nationwide
      Inpatient Sample, and emergency department data are from the National Hospital
      Ambulatory Medical Care Survey. RESULTS: A total of 347,484 (95% confidence
      interval = 308,417 to 386,551) emergency department presentations occur annually
      for injuries following a fall. Hospitalized patients older than 75 years of age
      had a 3.3% case fatality, and 42% were discharged to a skilled nursing facility.
      For patients older than 55 years of age, 86% of falls were not work related.
      CONCLUSIONS: Ladder and structure falls by elders are a substantial emergency
      department problem warranting thorough clinical evaluation and injury prevention
      efforts.

PMID- 15741594
TI  - Measuring the agreement between two tests for determining blood alcohol
      concentrations.

PMID- 15741595
TI  - How many footsteps do dogs need to determine the direction of an odour trail?
AB  - Dogs have the ability to determine the direction of an odour trail left by a
      human. This study examined how much olfactory information from this trail is
      required by dogs to determine direction. Six dogs, able to determine direction,
      were tested on a 21 footstep trail laid on 21 individual carpet squares, one
      footstep per square, by the same individual wearing the same shoes. Dogs brought
      in at right-angles to the trail at its centre were able to correctly determine
      direction better than chance (P < 0.025). Dogs were unable to determine direction
      when the order of the footsteps was randomized by rearranging the order of the
      carpet squares. When the individual odour cue was removed, but ground disturbance
      left, dogs were unable to determine direction, indicating that it was the odour
      of the individual that was used to determine direction. In the final experiment
      the number of footsteps made available to the dog was reduced from 21 to 11 and
      then 9, 7, 5 and finally 3. Dogs were able to determine direction from 5
      footsteps but not 3. It was calculated that it takes approximately 1-2 s for the
      odour information in footsteps to change to provide discernible information that
      can be used by dogs to determine direction. The process by which dogs may
      determine direction from odour cues is discussed.

PMID- 15741596
TI  - Characterization of bitter taste responses of intestinal STC-1 cells.
AB  - Cellular responses of STC-1 cells to two bitter tastants (denatonium and
      caffeine) were investigated using a calcium-imaging technique and compared with
      the response to bombesin. Caffeine is known to stimulate taste receptor cells,
      but the properties of its signaling have not been well studied. STC-1 cells
      responded to all three molecules in a dose-dependent manner, and when a reverse
      transcriptase-polymerase chain reaction (RT-PCR) for denatonium receptor was
      performed, the product of predicted size was detected in STC-1 cells.
      Furthermore, all three signaling pathways were blocked by a phospholipase C (PLC)
      inhibitor, demonstrating the essential involvement of PLC in cellular responses.
      To study the regulatory system of G protein signaling in STC-1 cells, we searched
      G protein-coupled receptor kinases (GRKs) by the degenerate-primer PCR method and
      found that GRK2 is expressed. We also demonstrated that three GRKs (GRK2, GRK3
      and GRK5) are differentially distributed in the circumvallate papilla while only
      GRK2 is present in taste bud cells. Finally, we overexpressed GRK2 in SCT-1 cells
      and found that bombesin-induced response was strongly inhibited by GRK2 but
      denatonium-activated signaling was not affected. In the case of caffeine,
      response was decreased by expression of GRK2 only when cells were activated by 1
      mM caffeine. Thus, we showed that STC-1 cells emerge as a cell model for studying
      the molecular mechanism of bitter taste signaling, and could indicate properties
      of caffeine-induced signaling in comparison with other signaling.

PMID- 15741597
TI  - Effects of chemical modification of lysine residues on the sweetness of lysozyme.
AB  - Lysozyme is a sweet-tasting protein with a sweetness threshold value of around 7
      microM. To clarify the effect of basicity at the side chain of lysine residues on
      the threshold values of sweetness, charge-specific chemical modifications such as
      guanidination, acetylation and phosphopyridoxylation of lysine residues were
      performed. Sensory analysis showed that the sweetness threshold value of lysozyme
      was not changed by guanidination, whereas it was increased markedly by
      acetylation and phosphopyridoxylation. To confirm the importance of the basicity
      in the lysine residues in detail, purification of acetylated (Ac-) and
      phosphopyridoxylated (PLP-) lysozymes using SP-ion exchange column chromatography
      was performed. The threshold values were not changed by modification with fewer
      than two residues (approximately 7 microM), whereas the threshold values
      significantly increased to 15 and 34 microM when tetra-Ac and tri-PLP,
      respectively. Furthermore, sweetness was not detected at 30 microM (hexa-, penta
      Ac and tetra-PLP). It should be noted that removal of the negative charges of the
      phosphate groups in the tri-PLP lysozyme by acid phosphatase resulted in the
      recovery of sweetness (6.4 microM), indicating that basicity at the position of
      the lysine residues is responsible for lysozyme sweetness and that strict charge
      complementarities might be required for interaction to its putative receptor.

PMID- 15741598
TI  - Biochemical and chemical supports for a transnatal olfactory continuity through
      sow maternal fluids.
AB  - Recognition of the mother is of major importance for the survival of mammalian
      neonates. This recognition is based, immediately after birth, on the detection of
      odours that have been learned by the fetus in utero. If the ethological basis of
      a transnatal olfactory continuity is well established, little is known on the
      nature of its olfactory cues, and nothing about the presence of potential carrier
      proteins in the maternal fluids such as amniotic fluid, colostrum and milk. We
      have identified the components of the pig putative maternal pheromone in these
      fluids of the sow. We also used a ligand-oriented approach to functionally
      characterize carrier proteins for these compounds in the maternal fluids. Six
      proteins were identified, using binding assay, immunodetection and peptide
      mapping by mass spectrometry. These proteins are known to transport hydrophobic
      ligands in biological fluids. Among them, alpha-1 acid glycoprotein (AGP) and
      odorant-binding protein (OBP) have been described in the oral sphere of piglets
      as being involved in the detection of pig putative maternal pheromone components.
      These are the first chemical and biochemical data supporting a transnatal
      olfactory continuity between the fetal and the postnatal environments.

PMID- 15741600
TI  - A method for the rapid automated assessment of olfactory function.
AB  - We have developed a strategy for the rapid high-throughput screening of odor
      responsivity in genetically altered mice (in fact, any experimentally altered
      animal). Specifically, the report presents the development and validation of a
      fully automated procedure based on the evaluation of an animal's stimulus-induced
      reflexive breathing response (i.e. sniffing behavior) to both air and odorant
      stimuli. The method requires no training of the animal to be screened and the
      outcome of the evaluation yields an operationally defined measure. Briefly, using
      whole-body plethysmography, the procedure determines the numerical values for a
      set of 14 respiratory measures in response to the presentation of air and a well
      above-threshold concentration of the odorant propanol. These measures of stimulus
      induced sniffing are incorporated into a model that defines a single univariate
      measure of response behavior, or 'Sniffing Index', for each screened animal. The
      approach significantly discriminated between the reflexive sniffing response of a
      control group of mice and that of an experimentally defined manipulated group for
      which, a priori, we expected to observe a robust altered breathing response to
      odorant stimulation (i.e. non-odor-aversion-conditioned versus odor-aversion
      conditioned C57BL/6J mice). Further, the procedure was able to significantly
      discriminate between a mutant phenotype with documented alterations in
      physiologic and behavioral function (namely, the OMP-null mutant), and their
      background strain. In addition, applying epidemiologic screening principles to
      the observed data, we established an operational procedure for the evaluation of
      unknown animals.

PMID- 15741601
TI  - Perceptual interactions in odour mixtures: odour quality in binary mixtures of
      woody and fruity wine odorants.
AB  - The qualitative perceptual interactions in three binary mixtures of wine odorants
      were studied: isoamyl acetate (fruity note)/whisky lactone (woody note), ethyl
      butyrate (fruity note)/whisky lactone (woody note) and ethyl butyrate (fruity
      note)/guaiacol (woody note). For each binary mixture, the perceived quality and
      intensity of 24 stimuli (four supra-threshold concentration levels of each of the
      two compounds and their 16 possible combinations) were evaluated in five
      replications by a trained panel of 13 subjects. The application of the Olsson
      predictive model for odour intensity and quality perception gave quite a good
      estimation of the evolution of single component identification in the mixture
      when the intensity proportion of unmixed components varied. However, this model
      was unable to account for the odour quality dominance in mixtures of iso-intense
      components. An alternative linear logistic model was proposed to study the
      qualitative dominance of the woody note in the three mixtures when the perceived
      intensities of each unmixed compound were equal.

PMID- 15741599
TI  - No relationship between sequence variation in protein coding regions of the
      Tas1r3 gene and saccharin preference in rats.
AB  - Nearly all mammalian species like sweet-tasting foods and drinks, but there are
      differences in the degree of 'sweet tooth' both between species and among
      individuals of the same species. Some individual differences can be explained by
      genetic variability. Polymorphisms in a sweet taste receptor (Tas1r3) account for
      a large fraction of the differences in consumption of sweet solutions among
      inbred mouse strains. We wondered whether mice and rats share the same Tas1r3
      alleles, and whether this gene might explain the large difference in saccharin
      preference among rats. We conducted three experiments to test this. We examined
      DNA sequence differences in the Tas1r3 gene among rats that differed in their
      consumption of saccharin in two-bottle choice tests. The animals tested were from
      an outbred strain (Sprague-Dawley; experiment 1), selectively bred to be high- or
      low-saccharin consumers (HiS and LoS; experiment 2), or from inbred strains with
      established differences in saccharin preference (FH/Wjd and ACI; experiment 3).
      Although there was considerable variation in saccharin preference among the rats
      there was no variation in the protein-coding regions of the Tas1r3 gene. DNA
      variants in intronic regions were detected in 1 (of 12) outbred rat with lower
      than-average saccharin preference and in the ACI inbred strain, which also has a
      lower saccharin preference than the FH/Wjd inbred partner strain. Possible
      effects of these intronic nucleotide variants on Tas1r3 gene expression or the
      presence of T1R3 protein in taste papillae were evaluated in the ACI and FH/Wjd
      strains. Based upon the results of these studies, we conclude that polymorphisms
      in the protein-coding regions of the sweet receptor gene Tas1r3 are uncommon and
      do not account for individual differences in saccharin preference for these
      strains of rats. DNA variants in intron 4 and 5 are more common but appear to be
      innocuous.

PMID- 15741602
TI  - Functional characterization of two human olfactory receptors expressed in the
      baculovirus Sf9 insect cell system.
AB  - Olfactory receptors (ORs) are the largest member of the G-protein-coupled
      receptors which mediate early olfactory perception in discriminating among
      thousands of odorant molecules. Assigning odorous ligands to ORs is a
      prerequisite to gaining an understanding of the mechanisms of odorant
      recognition. The functional expression of ORs represents a critical step in
      addressing this issue. Due to limitations in heterologous expression, very few
      mammal ORs have been characterized, and so far only one is from human origin.
      Consequently, OR function still remains poorly understood, especially in humans,
      whose genome encodes a restricted chemosensory repertoire compared with most
      mammal species. In this study, we have designed cassette baculovirus vectors to
      coexpress human OR 17-209 or OR 17-210 with either G(alpha olf) or G(alpha16)
      proteins in Sf9 cells. Each OR was found to be expressed at the cell surface and
      colocalized with both G(alpha) proteins. Using Ca2+ imaging, we showed that OR 17
      209 and OR 17-210 proteins are activated by esters and ketones respectively.
      Odorant-induced calcium response was increased when ORs were coexpressed with
      G(alpha16) protein, whereas coexpression with G(alpha olf) abolished calcium
      signaling. This strategy has been found to overcome most of the limitations
      encountered when expressing an OR protein and has permitted odorant screening of
      functional ORs. Our approach could thus be of interest for further expression and
      ligand assignment of other orphan receptor proteins.

PMID- 15741603
TI  - Metallic taste from electrical and chemical stimulation.
AB  - A series of three experiments investigated the nature of metallic taste reports
      after stimulation with solutions of metal salts and after stimulation with metals
      and electric currents. To stimulate with electricity, a device was fabricated
      consisting of a small battery affixed to a plastic handle with the anode side
      exposed for placement on the tongue or oral tissues. Intensity of taste from
      metals and batteries was dependent upon the voltage and was more robust in areas
      dense in fungiform papillae. Metallic taste was reported from stimulation with
      ferrous sulfate solutions, from metals and from electric stimuli. However,
      reports of metallic taste were more frequent when the word 'metallic' was
      presented embedded in a list of choices, as opposed to simple free-choice
      labeling. Intensity decreased for ferrous sulfate when the nose was occluded,
      consistent with a decrease in retronasal smell, as previously reported. Intensity
      of taste evoked by copper metal, bimetallic stimuli (zinc/copper) or small
      batteries (1.5-3 V) was not affected by nasal occlusion. This difference suggests
      two distinct mechanisms for evocation of metallic taste reports, one dependent
      upon retronasal smell and a second mediated by oral chemoreceptors.

PMID- 15741604
TI  - Stimulation of renal sulfate secretion by metabolic acidosis requires Na+/H+
      exchange induction and carbonic anhydrase.
AB  - The acute effect of metabolic acidosis on SO(4)(2-) secretion by the marine
      teleost renal proximal tubule was examined. Metabolic acidosis was mimicked in
      primary cultures of winter flounder renal proximal tubule epithelium (fPTCs)
      mounted in Ussing chambers by reducing interstitial pH to 7.1 (normally 7.7).
      fPTCs with metabolic acidosis secreted SO(4)(2-) at a net rate that was 40%
      higher than in paired isohydric controls (pH 7.7 on interstitium). The
      stimulation was completely blocked by the carbonic anhydrase inhibitor
      methazolamide (100 microM). Although Na(+)/H(+) exchange (NHE) isoforms 1, 2, and
      3 were identified in fPTCs by immunoblotting, administering EIPA (20 microM) to
      the interstitial and luminal bath solutions had no effect on net SO(4)(2-)
      secretion by fPTCs with a normal interstitial pH of 7.7. However, EIPA (20
      microM) blocked most of the stimulation caused by acidosis when applied to the
      lumen but not interstitium, demonstrating that induction of brush-border NHE
      activity is important. In the intact flounder, serum pH dropped 0.4 pH units (pH
      7.7 to 7.3, at 2-3 h) when environmental pH was lowered from 7.8 to approximately
      4.3. Whereas serum [SO(4)(2-)] was not altered by acidosis, renal tubular SO(4)(2
      ) secretion rate was elevated 200%. Thus metabolic acidosis strongly stimulates
      renal sulfate excretion most likely by a direct effect on active renal proximal
      tubule SO(4)(2-) secretion. This stimulation appears to be dependent on inducible
      brush-border NHE activity.

PMID- 15741605
TI  - Molecular mechanisms of enhanced renal cell division in protection against S-1,2
      dichlorovinyl-L-cysteine-induced acute renal failure and death.
AB  - Sustained activation of ERK 1/2 by a low dose (15 mg/kg ip) of S-1,2
      dichlorovinyl-l-cysteine (DCVC) 72 h before administration of a lethal dose of
      DCVC (75 mg/kg ip) enhances renal cell division and protects mice against acute
      renal failure (ARF) and death (autoprotection). The objective of this study was
      to determine correlation among extent of S-phase DNA synthesis, activation of
      transcription factors, expression of G(1)/S cyclins, cyclin-dependent kinases
      (CDKs), and CDK inhibitors downstream of ERK 1/2 following DCVC-induced ARF in
      autoprotection. Administration of the lethal dose alone caused a general
      downregulation or an unsustainable increase, in transcriptional and
      posttranscriptional events thereby preventing G(1)-S transition of renal cell
      cycle. Phosphorylation of IkappaBalpha was inhibited resulting in limited nuclear
      translocation of NF-kappaB. However, cyclin D1 expression was high probably due
      to transcriptional cooperation of AP-1. Cyclin D1/cyclin-dependent kinase 4
      (cdk4)-cdk6 system-mediated phosphorylation of retinoblastoma protein was
      downregulated due to overexpression of p16 at 24 h after exposure to the lethal
      dose alone. Inhibition of S-phase stimulation was confirmed by proliferating cell
      nuclear antigen assay (PCNA). This inhibitory response was prevented if the
      lethal dose was administered 72 h after the low priming dose of DCVC due to
      promitogenic effect of the low dose. NF-kappaB-DNA binding is not limited if mice
      were pretreated with the priming dose. Cyclin D1/cdk4-cdk6 expression stimulated
      by the priming dose of DCVC was unaltered even after the lethal dose in the
      autoprotected group, explaining higher phosphorylated-pRB and S-phase stimulation
      found in this group. These results were corroborated with PCNA
      immunohistochemistry. These findings suggest that the priming dose relieves the
      block on compensatory tissue repair by upregulation of promitogenic mechanisms,
      normally blocked by the high dose when administered without the prior priming
      dose.

PMID- 15741606
TI  - The spiny mouse (Acomys cahirinus) completes nephrogenesis before birth.
AB  - The spiny mouse is relatively mature at birth. We hypothesized that like other
      organs, the kidney may be more developed in the spiny mouse at birth, than in
      other rodents. If nephrogenesis is complete before birth, the spiny mouse may
      provide an excellent model with which to study the effects of an altered
      intrauterine environment on renal development. Due to its desert adaptation, the
      spiny mouse may have a reduced cortex-to-medulla ratio but an equivalent total
      nephron number to the C57/BL mouse. Kidneys were collected from fetal and
      neonatal spiny mice and sectioned for gross examination of metanephric
      development. Kidneys were collected from adult spiny mice (10 wk of age), and
      glomerular number, volume, and cortex-to-medulla ratios were determined using
      unbiased stereology. Nephrogenesis is complete in spiny mouse kidneys before
      birth. Metanephrogenesis begins at approximately day 18, and by day 38 of a 40
      day gestation, the nephrogenic zone is no longer present. Spiny mice have a
      significantly (P < 0.001) lower total nephron number compared with C57/BL mice,
      although the total glomerular volume is similar. The cortex-to-medulla ratio of
      the spiny mouse is significantly (P < 0.01) smaller. The spiny mouse is the first
      rodent species shown to complete nephrogenesis before birth. This makes it an
      attractive candidate for the study of fetal and neonatal kidney development and
      function. The reduced total nephron number and cortex-to-medulla ratio in the
      spiny mouse may contribute to its ability to highly concentrate its urine under
      stressful conditions (i.e., dehydration).

PMID- 15741607
TI  - Localization of the GLUT8 glucose transporter in murine kidney and regulation in
      vivo in nondiabetic and diabetic conditions.
AB  - Kidney disease is a major complication of diabetes, and poor glycemic control is
      associated with the development of diabetic nephropathy. The precise mechanisms
      that lead to diabetic kidney disease still remain largely unknown and are under
      current investigation. Because glucose transporters in the kidney play an
      important role in the local maintenance of intracellular glucose and plasma
      glucose homeostasis, the tissue distribution and regulation of glucose
      transporter GLUT8, a new member of the glucose transporter family with important
      functions in cellular survival, were examined. To understand the normal
      regulation of GLUT8 expression in response to metabolic signals, fasting and
      feeding conditions were studied. Additionally, GLUT8 expression was studied using
      two different models of insulin resistance, GLUT4-/- and db/db mice. GLUT8 was
      localized to glomerular podocytes and tubular epithelial cells in the distal
      portion of the nephron. Expression of GLUT8 in the kidney was influenced by
      plasma glucose levels in vivo. Podocytes in kidneys of diabetic db/db mice
      express higher levels of GLUT8 compared with nondiabetic db/m mice. Because
      podocytes play an important role in glomerulosclerosis development and high
      levels of glucose have been shown to induce apoptotic cell death in various
      kidney cells, these data may provide further insight into the pathogenesis of
      glomerulosclerosis and diabetic nephropathy.

PMID- 15741608
TI  - Defective expression of Tamm-Horsfall protein/uromodulin in COX-2-deficient mice
      increases their susceptibility to urinary tract infections.
AB  - Mice lacking a functional cyclooxygenase-2 (COX-2) gene develop abnormal kidneys
      that contain hypoplastic glomeruli and reduced proximal tubular mass, and they
      often die of renal failure. A comparison of kidney-specific gene expression
      between wild-type and COX-2-deficient mice by cDNA microarrays revealed that
      although more than 500 mRNAs were differentially expressed between the two
      strains of mice depending on their ages, the genes encoding pre-pro-epidermal
      growth factor (pre-pro-EGF) and Tamm-Horsfall protein (THP)/uromodulin were
      aberrantly expressed in the kidneys of COX-2 -/- mice at all stages of their
      development. Downregulation of EGF could potentially affect renal development,
      and THP/uromodulin gene has been implicated in abnormal kidney development and
      end-stage renal failure in humans. We assessed in detail mechanism of defective
      THP/uromodulin gene expression and its potential consequences in COX-2-deficient
      mice. Consistent with the microarray data, the steady-state levels of
      THP/uromodulin mRNA were severely reduced in the COX-2 -/- kidney. Furthermore,
      reduced expression of renal THP/uromodulin, as assessed by Western blot and
      immunohistological methods, was closely corroborated by a corresponding decline
      in the urinary secretion of THP/uromodulin in COX-2 -/- mice. Finally, we
      demonstrate that the bladders of COX-2 -/- mice, in contrast to those of the wild
      type mice, are highly susceptible to colonization by uropathogenic Escherichia
      coli.

PMID- 15741609
TI  - Isolation and characterization of the Xenopus oocyte plasma membrane: a new
      method for studying activity of water and solute transporters.
AB  - The intact Xenopus laevis oocyte is a useful model system for studying expressed
      water and solute transporters but suffers from a number of limitations, most
      notably large unstirred layers and other intracellular diffusion barriers. To
      overcome these, we have developed a method for isolating plasma membrane vesicles
      from oocytes. This approach facilitates more precise control of the
      intravesicular environment and virtually eliminates the problem of unstirred
      layers in kinetic experiments. The isolation procedure results in 50.6-fold
      enrichment of the plasma membrane marker alkaline phosphodiesterase compared with
      the homogenate. Markers of late endosomes/lysosomes and mitochondria were not
      enriched, and the endoplasmic reticulum was enriched only modestly.
      Permeabilities of native plasma membrane to water and urea were 8.1 x 10(-4) and
      5.6 x 10(-7) cm/s, respectively, values that are sufficiently low to classify
      them as barrier membranes. Phospholipid analysis by mass spectrometry showed the
      membrane, not including cholesterol, to be rich in phosphatidylcholine (35.8 mole
      percent), sphingomyelin (25.8 mole percent), and phosphatidylinositol (6.8 mole
      percent). Cholesterol concentration was 20.7 mole percent. Membrane vesicles
      isolated from oocytes expressing aquaporin-1 exhibited fourfold higher water
      permeability in stopped-flow experiments. Oocytes expressing mouse urea
      transporter A3 (UT-A3) exhibited 7.5-fold faster phloretin-inhibitable urea
      transport compared with water-injected controls. There was no difference in water
      permeability between these membrane vesicles, suggesting that UT-A3 is not a
      water carrier. In conclusion, we describe an improved method for the isolation of
      the oocyte plasma membrane that will allow the study of water and solute
      transport kinetics as well as substrate selectivity in heterologously expressed
      proteins.

PMID- 15741610
TI  - Voters and health care in the 2004 election.
AB  - Exit polls showed that health care was a second-tier issue in the 2004
      presidential race and that it was more important to Democratic than Republican
      voters. Those who considered health care the most important issue in their voting
      decision voted over-whelmingly for John Kerry. An analysis of national opinion
      surveys and exit polls shows that Republican and Democratic voters expressed
      dramatically differing views on key health policy issues. With the exception of
      malpractice reform and reducing federal health spending, health care is not
      likely to be a top issue for the Bush administration's second term.

PMID- 15741611
TI  - Early mortality after hip fracture: is delay before surgery important?
AB  - BACKGROUND: Hip fracture is associated with high mortality among the elderly.
      Most patients require surgery, but the timing of the operation remains
      controversial. Surgery within twenty-four hours after admission has been
      recommended, but evidence supporting this approach is lacking. The objective of
      this study was to determine whether a delay in surgery for hip fractures affects
      postoperative mortality among elderly patients. METHODS: We conducted a
      prospective, observational study of 2660 patients who underwent surgical
      treatment of a hip fracture at one university hospital. We measured mortality
      rates following the surgery in relation to the delay in the surgery and the acute
      medical comorbidities on admission. RESULTS: The mortality following the hip
      fracture surgery was 9% (246 of 2660) at thirty days, 19% at ninety days, and 30%
      at twelve months. Of the patients who had been declared fit for surgery, those
      operated on without delay had a thirty-day mortality of 8.7% and those for whom
      the surgery had been delayed between one and four days had a thirty-day mortality
      of 7.3%. This difference was not significant (p = 0.51). The thirty-day mortality
      for patients for whom the surgery had been delayed for more than four days was
      10.7%, and this small group had significantly increased mortality at ninety days
      (hazard ratio = 2.25; p = 0.001) and one year (hazard ratio = 2.4; p = 0.001).
      Patients who had been admitted with an acute medical comorbidity that required
      treatment prior to the surgery had a thirty-day mortality of 17%, which was
      nearly 2.5 times greater than that for patients who had been initially considered
      fit for surgery (hazard ratio = 2.3, 95% confidence interval = 1.6 to 3.3; p <
      0.001). CONCLUSIONS: The thirty-day mortality following surgery for a hip
      fracture was 9%. Patients with medical comorbidities that delayed surgery had 2.5
      times the risk of death within thirty days after the surgery compared with
      patients without comorbidities that delayed surgery. Mortality was not increased
      when the surgery was delayed up to four days for patients who were otherwise fit
      for hip fracture surgery. However, a delay of more than four days significantly
      increased mortality.

PMID- 15741612
TI  - Lumbar total disc replacement. Seven to eleven-year follow-up.
AB  - BACKGROUND: Symptomatic lumbar degenerative disc disease is a challenging entity
      to treat. The results of arthrodesis may be compromised in the short term by
      pseudarthrosis and in the long term by pain at the iliac-crest donor site and by
      junctional degeneration. Total disc replacement has the potential to provide long
      lasting relief to these patients. The purpose of this study was to present the
      clinical and radiographic results assessed seven to eleven years following a
      Prodisc total lumbar disc replacement. METHODS: Sixty-four patients had single or
      multiple-level implantation of a total lumbar disc replacement between 1990 and
      1993. The mean duration of follow-up was 8.7 years. Clinical results were
      evaluated by assessing preoperative and postoperative lumbar pain, radiculopathy,
      disability, and modified Stauffer-Coventry scores. Preoperative and postoperative
      radiographs were evaluated as well. Subgroup analysis was performed to determine
      if gender, an age of less than forty-five years, previous surgery, or multilevel
      surgery had an effect on outcome. RESULTS: At an average of 8.7 years
      postoperatively, there were significant improvements in the back-pain,
      radiculopathy, disability, and modified Stauffer-Coventry scores. Thirty-three of
      the fifty-five patients with sufficient follow-up had an excellent result, eight
      had a good result, and fourteen had a poor result. Neither gender nor multilevel
      surgery affected outcome. An age of less than forty-five years and prior lumbar
      surgery had small but significant negative effects on outcome. Radiographs did
      not demonstrate loosening, migration, or mechanical failure in any patient. Five
      patients had approach-related complications. CONCLUSIONS: The Prodisc lumbar
      total disc replacement appears to be effective and safe for the treatment of
      symptomatic degenerative disc disease. Gender and multilevel surgery did not
      affect the outcomes, whereas prior lumbar surgery or an age of less than forty
      five years was associated with slightly worse outcomes. Longer follow-up of this
      cohort of patients and randomized trials comparing disc replacement with
      arthrodesis are needed.

PMID- 15741613
TI  - Magnetic resonance imaging of the knee in children and adolescents. Its role in
      clinical decision-making.
AB  - BACKGROUND: Recent studies have questioned the utility of magnetic resonance
      imaging in the diagnosis of pediatric knee disorders because of the morphologic
      changes during growth and the low accuracy of the formal interpretation of the
      magnetic resonance imaging scan by a radiologist. The purpose of this study was
      twofold: (1) to report the accuracy of formal interpretations of magnetic
      resonance imaging scans of the knee in children and adolescent patients by a
      radiologist, and (2) to determine the benefit, if any, of a personal review of
      the magnetic resonance imaging scan of the knee by the orthopaedic surgeon, as a
      routine part of the diagnostic evaluation. METHODS: A three-year prospective
      study of all patients who underwent knee arthroscopy performed by a single
      surgeon, at two children's hospitals, was completed. The analysis focused on the
      six most common diagnoses: anterior cruciate ligament tear, lateral meniscal
      tear, medial meniscal tear, osteochondritis dissecans, discoid lateral meniscus,
      and osteochondral fracture. The preoperative diagnosis of the surgeon was
      determined by integrating the history and the findings on the clinical
      examination, plain radiographs, and magnetic resonance imaging scans (including
      the radiologist's interpretation). RESULTS: Ninety-six patients with ninety-six
      abnormal knees were included. The mean age was 14.6 years at the time of surgery.
      Relative to operative findings, kappa values for the formal interpretations of
      the magnetic resonance imaging scans by a radiologist were 0.78 for an anterior
      cruciate ligament tear, 0.76 for a medial meniscal tear, 0.71 for a lateral
      meniscal tear, 0.70 for osteochondritis dissecans, 0.46 for discoid lateral
      meniscus, and 0.65 for osteochondral fracture. Relative to operative findings,
      kappa values for the preoperative diagnoses by the surgeon were 1.00 for an
      anterior cruciate ligament tear, 0.90 for a medial meniscal tear, 0.92 for a
      lateral meniscal tear, 0.93 for osteochondritis dissecans, 1.00 for discoid
      lateral meniscus, and 0.90 for osteochondral fracture. The preoperative diagnosis
      by the surgeon was better (p < 0.05) than the formal interpretation of the
      magnetic resonance imaging scans by the radiologist with respect to an anterior
      cruciate ligament tear, lateral meniscal tear, osteochondritis dissecans, and
      discoid lateral meniscus. CONCLUSIONS: Integration of patient information with an
      orthopaedic surgeon's review of the magnetic resonance imaging scan of the knee
      in children and adolescent patients improves the identification of pathological
      disorders in four of the six categories evaluated. This study questions the
      necessity for and appropriateness of a routine interpretation of a magnetic
      resonance imaging scan of the knee in children and adolescents by a radiologist.

PMID- 15741614
TI  - Botulinum toxin injection in the treatment of tennis elbow. A double-blind,
      randomized, controlled, pilot study.
AB  - BACKGROUND: A recent report has suggested that local injection of botulinum toxin
      type A is an effective method of treatment for chronic tennis elbow. The toxin is
      thought to provide temporary paralysis of the painful common extensor origin,
      thereby allowing a healing response to occur. To test this theory, we performed a
      double-blind, randomized, controlled, pilot trial comparing injections of
      botulinum toxin type A with those of a placebo (normal saline solution) in the
      treatment of chronic tennis elbow. METHODS: Forty patients with a history of
      chronic tennis elbow for which all conservative treatment measures, including
      steroid injection, had failed were randomized into two groups. Half the patients
      received 50 units of botulinum toxin type A, and the remainder received normal
      saline solution. The intramuscular injections were performed 5 cm distal to the
      maximum point of tenderness at the lateral epicondyle, in line with the middle of
      the wrist. The two solutions used for the injections were identical in appearance
      and temperature. The results of a quality-of-life assessment with the Short Form
      12 (SF-12), the pain score on a visual analogue scale, and the grip strength
      measured with a validated Jamar dynamometer were recorded before and three months
      after the injection. RESULTS: Three months following the injections, there was no
      significant difference between the two groups with regard to grip strength, pain,
      or quality of life. CONCLUSIONS: With the numbers studied, we failed to find a
      significant difference between the two groups; thus, we have no evidence of a
      benefit from botulinum toxin injection in the treatment of chronic tennis elbow.

PMID- 15741615
TI  - Staggered bilateral total knee arthroplasty performed four to seven days apart
      during a single hospitalization.
AB  - BACKGROUND: The purpose of this study was to evaluate the types and prevalence of
      complications associated with bilateral total knee replacement performed four to
      seven days apart during a single hospitalization and to compare them with those
      associated with bilateral knee replacement performed sequentially under the same
      anesthetic session or staged unilateral replacements performed during separate
      hospitalizations. METHODS: Using a computerized database and medical records, we
      retrospectively evaluated 332 consecutive patients who underwent bilateral total
      knee replacement performed by two surgeons. A total of 241 patients underwent
      staggered bilateral knee replacement with the procedures performed four to seven
      days apart during one hospitalization, twenty-six underwent sequential bilateral
      total knee replacement, and sixty-five underwent staged bilateral knee
      replacement performed during two separate hospitalizations. The data on major
      complications, including death, return to operating room, myocardial infarction,
      and pulmonary embolism, and on minor complications, including atrial
      fibrillation, deep-vein thrombosis, and urinary tract infection, were evaluated.
      RESULTS: Patients undergoing sequential bilateral total knee replacement and
      staged bilateral knee replacement had an overall rate of complications that was
      2.5 times higher than that of the staggered group. Major complications were rare
      in all groups, but they occurred most often in the staged bilateral replacement
      group. The overall rate of complications for the patients who had staggered
      bilateral knee replacement (13%) was significantly less (p = 0.0009) than that
      for the patients who had sequential bilateral knee replacement (35%) or staged
      bilateral knee replacement (31%). The length of inpatient stay for those with
      staggered total knee arthroplasty was four days longer than that for the
      sequential arthroplasty group (p = 0.0001). CONCLUSIONS: Staggered bilateral
      total knee replacement, with the procedures performed four to seven days apart in
      a single hospitalization, is a safe and practical method for performing bilateral
      total knee replacement.

PMID- 15741616
TI  - Rotational acetabular osteotomy for osteonecrosis with collapse of the femoral
      head in young patients.
AB  - BACKGROUND: While rotational acetabular osteotomy has been reported to be
      successful for the treatment of osteoarthritis of the dysplastic hip, little is
      known about its efficacy in the treatment of osteonecrosis of the femoral head.
      METHODS: We retrospectively reviewed the results for a consecutive series of
      twenty-one patients (twenty-five hips) who had undergone rotational acetabular
      osteotomy between 1995 and 2001 for the treatment of extensive osteonecrosis of
      the femoral head associated with collapse. All but two of the patients had a
      history of steroid therapy as part of a treatment regimen for various diseases.
      At the time of surgery, the mean age of the five men and sixteen women was 29.0
      years. The mean duration of follow-up was forty-nine months. No patient was lost
      to follow-up. The lesions were classified according to the staging system
      described by Steinberg et al., and the extent of necrosis was measured with use
      of the criteria described by Kerboul et al. Clinical evaluation was performed
      with use of the scoring system of Merle d'Aubigne and Postel. Radiographic
      evaluation was performed with use of yearly serial anteroposterior and lateral
      plain radiographs. RESULTS: The mean Merle d'Aubigne and Postel score improved
      from 11.3 points preoperatively to 14.9 points at the time of the final follow-up
      (p < 0.001). The mean pain score improved from 3.0 to 5.6 points (p < 0.001).
      However, the mean mobility score was 5.3 points preoperatively but only 4.9
      points postoperatively (p = 0.1). All of the osteotomy sites showed radiographic
      evidence of osseous union at the time of the latest follow-up. Collapse of the
      femoral head progressed in seven hips, but in six of these hips the change in the
      extent of collapse was <2 mm. CONCLUSIONS: In the present study of young patients
      with extensive osteonecrosis and collapse of the femoral head, rotational
      acetabular osteotomy was associated with symptomatic relief and absence of
      substantial collapse of the femoral head at the time of early to intermediate
      term follow-up.

PMID- 15741617
TI  - Mechanical effects of the extended trochanteric osteotomy.
AB  - BACKGROUND: The extended trochanteric osteotomy was introduced as a safe and
      effective exposure technique for revision hip surgery; however, intraoperative
      iatrogenic femoral fractures have been reported. This study examined the effects
      of the extended trochanteric osteotomy on the torsional strength of the femur
      with use of cadaver bones. We hypothesized that repair of the osteotomy fragment
      would restore the torsional strength to that of an intact femur and that an
      osteotomized femur containing a well-fixed stem would have the same torsional
      strength as an intact femur with a stem. METHODS: Fifty-eight cadaveric human
      femora were divided into five groups, according to the repair technique, to
      examine the effects of the extended trochanteric osteotomy: intact, osteotomy,
      repaired osteotomy, implant, and implant-repaired osteotomy. Osteotomy fragments
      were reattached with use of three double-looped 18-gauge wires. A femoral stem
      was cemented into the last two groups. Specimens were tested mechanically in
      rotation until failure. Rotational properties were compared with one-way analysis
      of variance followed by post hoc pairwise comparisons. Linear regression analysis
      was performed for bone mineral density and torsional strength. RESULTS: Torque to
      failure was reduced by 73% for the specimens in the osteotomy group compared with
      the intact group (p < 0.0001). Repair of the osteotomy did not improve torque to
      failure (p > 0.99). Femora in the implant-repaired osteotomy group displayed
      significantly improved torque-to-failure values compared with the specimens in
      the osteotomy and repaired osteotomy groups (p < 0.0001). However, the strength
      of the femora in the implant-repaired osteotomy group remained significantly less
      than that of the specimens in the implant group (p < 0.007). A significant linear
      relationship was observed between bone mineral density and torque to failure for
      femora in the intact (p < 0.006), osteotomy (p < 0.002), and repaired osteotomy
      (p < 0.001) groups. CONCLUSIONS: The extended trochanteric osteotomy reduces
      torsional strength by 73% even when the osteotomy fragment is repaired. Bone
      mineral density directly affects absolute femoral strength in this model.

PMID- 15741618
TI  - Alumina-on-alumina total hip arthroplasty. A five-year minimum follow-up study.
AB  - BACKGROUND: Ceramic-on-ceramic couplings are attractive alternative bearing
      surfaces that have been reported to eliminate or reduce problems related to
      polyethylene wear debris. Disappointing experiences with alumina ceramic bearings
      in the past have led to many improvements in the manufacture and design of
      ceramic implants. The purpose of the present study was to report the results of
      contemporary alumina-on-alumina total hip arthroplasties with regard to wear,
      osteolysis, and fracture of the ceramic after a minimum duration of follow-up of
      five years. METHODS: We evaluated the results of a consecutive series of 100
      primary alumina-on-alumina total hip arthroplasties that had been performed with
      use of a metal-backed socket and a cementless stem in eighty-four patients. All
      of the patients were sixty-five years of age or younger (mean age, forty-one
      years), and a single surgeon performed all of the procedures. After a minimum
      duration of follow-up of sixty months, one patient (one hip) had died and four
      patients (six hips) had been lost to follow-up, leaving a total of seventy-nine
      patients (ninety-three hips) available for study. All of these patients were
      evaluated clinically and radiographically with special attention to wear,
      periprosthetic osteolysis, and ceramic failure. RESULTS: The mean Harris hip
      score was 97 points at the time of the latest follow-up evaluation. All
      prostheses demonstrated radiographic evidence of bone ingrowth. No implant was
      loose radiographically, and no implant was revised. Ceramic wear was not
      detectable in the thirty-seven hips in which the femoral head could be
      differentiated from the cup on radiographs. Periprosthetic osteolysis was not
      observed in any hip. A fracture of the alumina femoral head and a peripheral chip
      fracture of the alumina insert occurred in one hip following a motor-vehicle
      accident. CONCLUSIONS: The results of contemporary alumina-on-alumina total hip
      arthroplasty with a metal-backed socket and a cementless stem were encouraging
      after a minimum duration of follow-up of five years. We believe that these
      improved alumina-on-alumina bearing implants offer a promising option for
      younger, active patients.

PMID- 15741619
TI  - The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion.
AB  - BACKGROUND: Cyclooxygenase (COX)-2-specific inhibitors demonstrate analgesic
      efficacy comparable with that of conventional nonsteroidal anti-inflammatory
      drugs but are associated with reduced gastrointestinal side effects and an
      absence of antiplatelet activity. Thus, they can be administered to patients
      undergoing spinal fusion surgery without an added risk of bleeding. However,
      concerns regarding a possible deleterious effect on bone-healing have limited
      their routine use. Celecoxib, a COX-2 inhibitor, recently was approved for the
      treatment of acute pain. The goals of the present study were to examine the
      analgesic efficacy of celecoxib and to determine the incidence of nonunion at one
      year following spinal fusion surgery. METHODS: Eighty patients who were scheduled
      to undergo spinal fusion received either celecoxib or placebo one hour before the
      induction of anesthesia and every twelve hours after surgery for the first five
      postoperative days. Pain scores and morphine use were recorded one hour after
      arrival in the post-anesthesia care unit and at four, eight, twelve, sixteen,
      twenty, and twenty-four hours later. Intraoperative blood loss was recorded. The
      status of the fusion was determined radiographically at the time of the one-year
      follow-up. RESULTS: There were no differences in demographic data or blood loss
      between the two groups. Pain scores were lower in the celecoxib group at one,
      four, eight, sixteen, and twenty hours postoperatively. There were no differences
      between the two groups with regard to the pain scores at twelve and twenty-four
      hours postoperatively. Morphine use was lower in the celecoxib group at all
      postoperative time-intervals. There was no difference between the celecoxib group
      and the placebo group with regard to the incidence of nonunion at the time of the
      one-year follow-up (7.5% [three of forty] compared with 10% [four of forty]).
      CONCLUSIONS: The perioperative administration of celecoxib resulted in a
      significant reduction in postoperative pain and opioid use following spinal
      fusion surgery. In addition, the short-term administration of this COX-2-specific
      non-steroidal anti-inflammatory drug had no apparent effect on the rate of
      nonunion at the time of the one-year follow-up.

PMID- 15741620
TI  - Idiopathic slipped capital femoral epiphysis in Amish children.
AB  - BACKGROUND: Of the many studies of slipped capital femoral epiphysis, none have
      specifically addressed Amish children. The Amish reflect a small gene pool
      relative to the general white North American population. Additional knowledge of
      the demographics of this disorder in Amish children may provide genetic insights.
      The purpose of this study was to review the demographics of slipped capital
      femoral epiphysis in the Amish population. METHODS: A retrospective review of the
      cases of twenty-five Amish children with slipped capital femoral epiphysis
      treated at two institutions was performed. The child's gender, age, weight,
      height, and body mass index at the time of the diagnosis; duration of symptoms;
      laterality of the slip; birth weight; family history; and slip severity were
      recorded. The slip was classified as stable or unstable. Patients who had been
      included in a previously published multicenter study served as a control group.
      RESULTS: There were seventeen boys and eight girls with a total of thirty-three
      slipped capital femoral epiphyses; eight of the slips were bilateral. At the time
      of the diagnosis, the mean age (and standard deviation) was 13.4 +/- 1.6 years,
      the mean weight and height were 55.6 +/-12.4 kg and 155.5 +/- 10.2 cm, and the
      mean body mass index was 23.4 +/- 5.4 kg/m(2). The mean duration of symptoms was
      6.6 +/-9.0 months. There were thirty-one stable and two unstable slips with a
      mean slip angle of 38 degrees +/- 20 degrees . Nine (39%) of twenty-three
      children for whom the information had been recorded had a positive family history
      of slipped capital femoral epiphysis, a rate that is higher than the 9% and 14.5%
      rates reported in two other series (p = 0.002). The Amish children were not as
      heavy as their non-Amish counterparts (55.6 +/- 12.4 kg compared with 66.4 +/-
      17.7 kg, p = 0.0036). CONCLUSIONS: Although the children in this study were
      moderately heavy, they could not be classified as obese on the basis of weight
      for-age or body-mass-index percentiles. The high prevalence of family members
      with slipped capital femoral epiphysis may reflect either a genetic or
      environmental component, or an interaction between genetics and environment (for
      example, work load or common chores requiring particular physical positions) in
      the Amish population.

PMID- 15741621
TI  - Ibandronate for prevention of femoral head deformity after ischemic necrosis of
      the capital femoral epiphysis in immature pigs.
AB  - BACKGROUND: Femoral head deformity is the most serious sequela of ischemic
      necrosis of the immature femoral head. The purpose of this study was to determine
      if a highly potent antiresorptive agent, ibandronate, can inhibit bone resorption
      during the repair of the infarcted femoral head and thus alter the repair
      process. We hypothesized that preservation of the trabecular framework by
      inhibiting osteoclastic bone resorption would minimize the development of
      deformity in a piglet model of ischemic necrosis. The effect of ibandronate on
      long-bone growth was also assessed. METHODS: Ischemic necrosis of the right
      femoral head was produced in twenty-four piglets by placing a ligature tightly
      around the femoral neck. The animals were divided into three groups according to
      whether they received saline solution, prophylactic treatment, or post-ischemia
      treatment. The contralateral, untreated femoral heads from the animals that had
      received saline solution served as the normal control group. At eight weeks, the
      femoral heads were assessed for deformity with radiography and for trabecular
      bone indices with histomorphometry. Also, the length of femur from the untreated
      side was measured on the radiographs and compared among the groups. RESULTS:
      Radiographic assessment showed that the epiphyseal quotient, determined by
      dividing the maximum height of the osseous epiphysis by the maximum diameter, was
      better preserved in the prophylactic (p < 0.001) and post-ischemia (p = 0.02)
      treatment groups than in the group treated with saline solution.
      Histomorphometric assessment also showed that the trabecular bone indices were
      better preserved in the prophylactic and the post-ischemia treatment groups than
      in the group treated with saline solution (p < 0.01). The mean femoral length on
      the untreated side of the animals treated with ibandronate was reduced compared
      with the length on the untreated side of the animals that had received saline
      solution (p </= 0.01). CONCLUSIONS: Ibandronate preserves the trabecular
      structure of the osseous epiphysis and prevents femoral head deformity during the
      early phase of repair of ischemic necrosis in the piglet model.

PMID- 15741622
TI  - Development of adjacent-level ossification in patients with an anterior cervical
      plate.
AB  - BACKGROUND: It has been our experience that ossification occurs adjacent to
      anterior cervical plates. Our hypothesis was that the closer the plate is to the
      adjacent disc space, the greater the ossification. METHODS: We retrospectively
      reviewed the lateral radiographs of the cervical spine of 118 patients who had a
      solid fusion following an anterior cervical arthrodesis with a plate for the
      treatment of a degenerative cervical condition; none of the patients had had
      cervical spine surgery prior to the index arthrodesis. The plate-to-disc distance
      was measured on the postoperative lateral radiograph and was used to divide the
      patients into two groups for each of the two adjacent disc spaces. In group A the
      plate-to-disc distance was <5 mm, and in group B it was >/=5 mm. The mean
      duration of follow-up was 25.7 months. The severity of the ossification at the
      two adjacent disc spaces was classified on a scale ranging from grade 0 (no
      ossification) to grade 3 (complete bridging). Eighteen patients were excluded
      from the measurement of the severity of the caudal ossification because
      overlapping by the bone of the shoulder precluded adequate visualization of the
      caudal level. RESULTS: Ossification developed in seventy (59%) of the 118
      cephalad adjacent disc spaces and twenty-nine (29%) of the 100 caudal adjacent
      disc spaces (p < 0.001). The mean cephalad plate-to-disc distance was shorter
      than the mean caudal plate-to-disc distance (p < 0.001). The rate of ossification
      was higher in group A than in group B, both at the cephalad adjacent disc spaces
      (67% compared with 24%) and at the caudal adjacent disc spaces (45% compared with
      5%) (both p < 0.001). In addition, 93% (twenty-six) of the twenty-eight cases of
      moderate-to-severe ossification developed in group A. CONCLUSIONS: We found a
      positive association between adjacent-level ossification following anterior
      cervical plate procedures and the plate-to-disc distance. We now strive to place
      anterior cervical plates at least 5 mm away from the adjacent disc spaces in
      order to decrease the likelihood of moderate-to-severe adjacent-level
      ossification.

PMID- 15741623
TI  - The association between supracondylar-intercondylar distal femoral fractures and
      coronal plane fractures.
AB  - BACKGROUND: Isolated coronal plane fractures of the distal femoral condyles
      (Hoffa fractures) occur uncommonly, are difficult to diagnose, and may be
      challenging to treat. The combination of supracondylar distal femoral fractures
      and these coronal plane fractures is thought to occur rarely. The purposes of the
      present study were to identify the frequency of the association between
      supracondylar-intercondylar distal femoral fractures and coronal fractures of the
      femoral condyle and to describe the radiographic evaluation of these injuries.
      METHODS: One hundred and eighty-nine patients with 202 supracondylar
      intercondylar distal femoral fractures were retrospectively evaluated clinically
      and radiographically. RESULTS: Coronal plane fractures were diagnosed in
      association with seventy-seven (38.1%) of the 202 supracondylar-intercondylar
      distal femoral fractures. Fifty-nine (76.6%) of these coronal fractures involved
      a single condyle, and eighteen involved both the medial and lateral femoral
      condyles. Eighty-five percent of the coronal fractures involving a single condyle
      were located laterally. Patients with an open distal femoral fracture were 2.8
      times more likely to have a coronal plane fracture than patients with a closed
      fracture were (95% confidence interval, 1.54 to 5.25). Coronal plane fractures
      were diagnosed in 47% of the 102 knees that were evaluated with computerized
      tomography, compared with 29% of the 100 knees that were not (p = 0.008). Ten
      coronal plane fractures that had been unrecognized preoperatively were identified
      only at the time of operative fixation of the distal femoral fracture; none of
      these fractures occurred in patients who had been evaluated with computerized
      tomographic scanning preoperatively. CONCLUSIONS: Coronal plane fractures
      frequently occurred in association with high-energy supracondylar-intercondylar
      distal femoral fractures; in the present study, the prevalence of associated
      coronal plane fractures was 38%. The lateral condyle was involved more frequently
      than the medial condyle was. Coronal plane fractures of both condyles were
      observed commonly, and the majority of coronal plane fractures were associated
      with open wounds. Since the surgical tactic for the treatment of a supracondylar
      intercondylar distal femoral fracture may be altered by the additional diagnosis
      of a coronal plane fracture component, preoperative computerized tomographic
      scanning of the injured distal part of the femur, particularly when there is an
      associated open wound, is strongly recommended.

PMID- 15741624
TI  - Hospital resource utilization for primary and revision total hip arthroplasty.
AB  - BACKGROUND: Previous reports have suggested that hospital resource utilization
      for revision total hip arthroplasty is substantially higher than that for primary
      total hip arthroplasty. However, current United States Medicare hospital
      reimbursement policy does not distinguish between the two procedures. The purpose
      of this study was to compare primary and revision total hip arthroplasties with
      regard to actual hospital resource utilization and to identify clinical and
      demographic factors that are predictive of higher resource utilization associated
      with these procedures. METHODS: We evaluated the clinical, demographic, and
      economic data associated with 491 consecutive unilateral primary or revision
      total hip arthroplasties performed by two surgeons at a single institution
      between January 2000 and December 2002. The distributions of various demographic,
      clinical, and utilization characteristics were compared between the two types of
      arthroplasty procedures, and multivariable linear regression techniques were used
      to determine independent patient characteristics that were predictive of higher
      costs for both the primary and the revision procedures. RESULTS: The mean total
      hospital cost was $31,341 for the revision procedures compared with $24,170 for
      the primary procedures (p < 0.0001). The mean operative time was 41% longer for
      the revisions than for the primary procedures (4.5 hours compared with 3.2 hours,
      p < 0.0001), the mean estimated blood loss was 160% higher (1348 mL compared with
      518 mL, p < 0.0001), the mean complication rate was 32% higher (29% compared with
      22%, p = 0.072), and the mean length of the hospital stay was 16% longer (6.5
      days compared with 5.6 days, p = 0.0005). A higher severity-of-illness score (a
      measure of preoperative medical health) was predictive of higher resource
      utilization for both primary and revision arthroplasty even after adjustment for
      other factors. Preoperative femoral and ace-tabular bone loss and a diagnosis of
      periprosthetic fracture were predictive of higher resource utilization associated
      with revision procedures. CONCLUSIONS: At one institution, hospital resource
      utilization for revision total hip arthroplasty was found to be significantly
      higher than that for primary arthroplasty. This information is not reflected by
      current United States Medicare hospital reimbursement, which is the same for all
      lower-extremity arthroplasty procedures, regardless of the diagnosis, the
      complexity of the procedure, or the patient's baseline medical health. If these
      findings are generalizable to other institutions, appropriate reimbursement
      formulas should be developed to accurately reflect the true costs of caring for
      patients with a failed total hip arthroplasty.

PMID- 15741625
TI  - Surface roughness of ceramic femoral heads after in vivo transfer of metal:
      correlation to polyethylene wear.
AB  - BACKGROUND: A dark metallic-appearing smear, resembling a lead pencil mark, may
      be seen on a ceramic femoral head component at revision total hip arthroplasty.
      The purpose of this study was to investigate the hypothesis that such a mark on a
      retrieved ceramic femoral head is associated with increased surface roughness of
      the head and increased polyethylene liner wear in total hip replacement. METHODS:
      Fifteen ceramic prosthetic femoral heads retrieved from fifteen patients at
      revision arthroplasty were examined in this study. Thirteen heads had been in
      vivo for an average of 10.8 years (range, 7.8 to 14.2 years). The remaining two
      heads had been in vivo for less than one month. The surface roughness
      characteristics of the explanted ceramic heads, the linear wear of the
      polyethylene liner, and the patient activity levels after the primary replacement
      and before the revision were determined. RESULTS: Four of the thirteen ceramic
      heads that had been in vivo for >/=7.8 years had severe smears (>6% of the
      surface area), and the remaining nine heads had slight smears (<6% of the surface
      area). The two heads that had been in vivo less than one month had severe smears.
      The mean Ra and Rpm, the values for surface roughness, were 44.95 nm and 571.15
      nm, respectively, in the hips with slightly smeared regions and 180.77 nm and
      1245.88 nm, respectively, in the hips with severely smeared regions (p = 0.002).
      The mean linear liner wear rate was 0.10 mm/yr in the hips with slightly smeared
      heads and 0.19 mm/yr in the hips with severely smeared heads (p = 0.002). The
      activity score for all patients was 5 or 6 points on a 6-point scale.
      CONCLUSIONS: The results of this study confirm the hypothesis that a visual dark
      metallic-appearing smear on a ceramic femoral head correlates with increased
      surface roughness of the head and increased polyethylene wear. These findings
      imply that contact of a ceramic femoral head with a metallic material, such as
      may occur with femoral head reduction or dislocation of a total hip replacement,
      is best avoided to prevent this metallic smear phenomenon.

PMID- 15741626
TI  - Thermal tissue damage caused by ultrasonic cement removal from the humerus.
AB  - BACKGROUND: Ultrasound devices can selectively remove cement during revision
      arthroplasty. These instruments initially were designed for the hip and knee but
      also have been applied to the upper extremity. We describe a patient in whom a
      radial nerve palsy and a pathologic humeral fracture developed after ultrasonic
      cement removal was performed because of an infection at the site of a total elbow
      arthroplasty. Biopsies of the humerus, the triceps muscle, and the radial nerve
      showed widespread necrosis consistent with thermal injury. METHODS: A study
      involving six human cadaveric specimens was conducted to measure temperature
      elevations in bone and adjacent soft tissue during cement removal with use of an
      ultrasound device with and without irrigation. RESULTS: While temperature
      increased only minimally during cement polymerization, ultrasonic melting and
      removal of cement with use of constant energy delivery led to markedly elevated
      temperatures in the humeral cortex, the triceps muscle, and the radial nerve.
      These temperatures were above the known thresholds for thermal injury and
      necrosis. Subsequently, strategies designed to allow for safe ultrasonic cement
      removal from the humerus were applied, including intermittent delivery of energy
      and the use of cold irrigation between probe passes. These strategies resulted in
      markedly lower maximum temperatures in all tissues tested. CONCLUSIONS:
      Temperatures in the humerus, triceps, and, most importantly, the radial nerve can
      reach potentially dangerous levels when ultrasound technology is used to remove
      cement from the humerus. We suggest intermittent cold irrigation of the humeral
      canal, no tourniquet use, education of surgeons with regard to proper techniques
      designed to limit heat generation, and consideration of exposure and protection
      of the radial nerve when ultrasound devices are used.

PMID- 15741627
TI  - Computed tomography in the assessment of periacetabular osteolysis.
AB  - BACKGROUND: Computed tomography recently has been proposed as an accurate method
      for diagnosing periacetabular osteolytic lesions. Several investigators have
      attempted to validate the accuracy of this technique, but they employed cadaveric
      and animal models, which cannot replicate the adaptive changes that occur over
      time in vivo. This study was performed to determine the accuracy of computed
      tomography in identifying and measuring periacetabular osteolytic lesions in
      hemipelves retrieved at autopsies of individuals with a previously well
      functioning total hip prosthesis. METHODS: We evaluated nine hemipelves,
      retrieved at autopsy, that contained a cementless porous-coated acetabular
      component. The fresh specimens were examined with conventional radiographs and
      computed tomography and then were embedded and sectioned into 1.5-mm slices for
      evaluation with slab radiographs. Anteroposterior and iliac oblique plain
      radiographs as well as axial, coronal, and sagittal computed tomography scans
      were reviewed to determine the presence and location of any periacetabular
      osteolytic lesions. These results were then compared with those identified on the
      slab radiographs. Lesion volume was calculated from computed tomography scans
      with use of post-processing software. RESULTS: A total of twenty-three
      periacetabular osteolytic lesions were identified on the slab radiographs of the
      nine hemipelves. The plain radiographs identified twelve (52%) of the twenty
      three lesions, and the computed tomography scans identified twenty (87%) of the
      twenty-three lesions. Three medial wall perforations were identified on the
      computed tomography scans but were not detected on the plain radiographs.
      Computed tomography was accurate in measuring the volume of the osteolytic
      lesions (r(2) = 0.997) but tended to overestimate the volumes measured on the
      slab radiographs. Periacetabular osteolytic lesions appeared on the computed
      tomography scans and slab radiographs as areas devoid of trabecular bone that
      were delineated by a sclerotic border and communicated with the joint space.
      CONCLUSIONS: In this autopsy model, computed tomography was an accurate method
      for detecting the location and measuring the volume of periacetabular osteolytic
      lesions.

PMID- 15741628
TI  - Modular fixed-bearing total knee arthroplasty with retention of the posterior
      cruciate ligament. A study of patients followed for a minimum of fifteen years.
AB  - BACKGROUND: There have been a limited number of studies of total knee
      arthroplasties with durations of follow-up of fifteen years, but we are not aware
      of any involving modular fixed-bearing posterior cruciate-retaining prostheses.
      METHODS: A consecutive series of 139 total knee arthroplasties in 109 patients
      (average age, sixty-seven years), performed by one surgeon using a nonconforming
      posterior cruciate-retaining prosthesis, was followed for fifteen years or
      longer. Forty-five patients (fifty-nine knees) were examined at a minimum of
      fifteen years postoperatively, fifty-seven patients (seventy knees) had died,
      five patients (eight knees) were too ill to return for assessment, and two
      patients (two knees) were considered lost to follow-up. The patients were
      assessed clinically with use of the Knee Society clinical rating system, and the
      knees were assessed radiographically. Survivorship analysis was performed with
      use of worst-case-scenario analysis and with failure defined as a reoperation for
      any reason. RESULTS: There were five reoperations, four of which were performed
      because of wear of the polyethylene insert. In addition, one loose cemented
      femoral component was revised at fifteen years. The survival rate without
      revision or a need for any reoperation was 92.6% at fifteen years. The mean Knee
      Society score and functional score at fifteen years were 96 and 78 points,
      respectively. The prevalence of radiolucent lines was 13%, with 2% around the
      femur, 11% around the tibia, and none around the patella. None of these lines
      were clinically relevant. There was no evidence of progressive radiolucent lines,
      and there was one case of asymptomatic femoral osteolysis. CONCLUSIONS: In this
      single-surgeon series, modular fixed-bearing posterior cruciate-retaining total
      knee arthroplasties had good clinical and radiographic results with excellent
      survivorship for up to fifteen years. These results are comparable with those in
      long-term studies of posterior stabilized implants and of prostheses with mobile
      bearing and nonmodular tibial inserts.

PMID- 15741629
TI  - Infections of the spine in patients with human immunodeficiency virus.
AB  - BACKGROUND: Musculoskeletal infections in patients with the human
      immunodeficiency virus (HIV) have been described. However, the prevalence,
      specific characteristics, and outcomes of spinal infections in these patients
      have not been studied in a large group of patients to our knowledge. METHODS: The
      computerized records of all patients discharged with the diagnosis of spinal
      osteomyelitis, discitis, epidural abscess, or tuberculosis from our institution
      from October 1994 through September 2000 were reviewed. Patients with the
      diagnosis of HIV were identified, and the charts were examined in detail.
      RESULTS: During the six-year period, 7338 unique patients who were HIV positive
      were admitted. Seventeen (0.23%) of them were treated for a spinal infection. The
      prevalence of spinal infection was 23.2 per 10,000 admissions of HIV-positive
      patients and 7.1 per 10,000 admissions of HIV-negative patients (p < 0.0001).
      Eight patients who had discitis and/or osteomyelitis had a mean CD4 T-cell count
      of 339.6 cells/mm(3), and all eight had clinical resolution of the infection
      after six to twelve weeks of appropriate antibiotic therapy. In contrast, six
      patients who had spinal tuberculosis had a mean CD4 count of 75.7 cells/mm(3) (p
      = 0.005), and one of them died during the hospitalization. The remaining three
      patients, who had epidural abscesses, had a mean CD4 count of 20.67 cells/mm(3)
      (p = 0.001), and two of them died. CONCLUSIONS: Discitis and/or osteomyelitis
      occurs in HIV-positive patients with a mild-to-moderate decrease (>/=200
      cells/mm(3)) in the CD4 T-cell count, and the infection responds to appropriate
      antibiotics. Patients with a more severely decreased CD4 count (50 to 200
      cells/mm(3)) may have spinal tuberculosis develop, and patients with the lowest
      CD4 counts are more likely to have epidural abscesses develop. The three
      fatalities in this study occurred in these two groups of patients. As a group,
      HIV-positive patients are significantly more likely to have a spinal infection
      develop than are HIV-negative patients (p < 0.0001). Although the CD4 count can
      be used as a predictor of the clinical course, identification of the organism
      remains paramount in the treatment of this complex patient population.

PMID- 15741630
TI  - Ossification of the posterior longitudinal ligament. Results of anterior cervical
      decompression and arthrodesis in sixty-one North American patients.
AB  - BACKGROUND: Ossification of the posterior longitudinal ligament is commonly
      associated with cervical myelopathy. Surgical treatment is a matter of
      controversy. We report on a series of patients who were managed with anterior
      cervical decompression and arthrodesis for the treatment of cervical myelopathy
      associated with ossification of the posterior longitudinal ligament. METHODS: We
      retrospectively reviewed the records for all sixty-five patients who had been
      managed with anterior decompression and arthrodesis for the treatment of cervical
      ossification of the posterior longitudinal ligament and associated neurologic
      compression from 1982 to 2001. Sixty-one patients (thirty-nine men and twenty-two
      women) were followed for at least two years (or until the time of death). The
      average number of vertebrae resected was 2.2. The average duration of follow-up
      for the sixty surviving patients was four years (range, two years to fifteen
      years and four months). The preoperative, six-week postoperative, and final
      follow-up clinical status (including neurological function as assessed with the
      Nurick grading system) was recorded for each patient. RESULTS: Fifty-six of the
      sixty-one patients had neurological improvement, with an average improvement of
      1.5 Nurick grades at the time of the final follow-up. Eight patients had absent
      dura at the time of surgery and, of these, five had development of a
      cerebrospinal fluid fistula. Eight patients had development of new neurological
      signs and/or symptoms in the upper extremity postoperatively. Eight patients
      required reoperation because of a painful pseudarthrosis (one patient), strut
      graft dislodgment (three), cerebrospinal fluid leakage (three), or compression of
      a nerve root caudad to the area of the original procedure (one). One patient died
      as the result of cardiac arrest on the third postoperative day. Fifty-eight
      patients had an osseous fusion, one had an asymptomatic nonunion, and one had a
      symptomatic pseudarthrosis that was treated with revision surgery. CONCLUSIONS:
      Anterior decompression and arthrodesis is an effective way to achieve pain relief
      and neurological improvement in North American patients of non-Asian descent who
      have cervical myelopathy associated with ossification of the posterior
      longitudinal ligament. The risk of durocutaneous fistula, graft dislodgment, and
      postoperative neurological symptoms appears to be high in patients with cervical
      myelopathy associated with this condition.

PMID- 15741631
TI  - Chondrolysis following arthroscopic thermal capsulorrhaphy to treat shoulder
      instability. A report of two cases.

PMID- 15741632
TI  - Use of topical negative pressure in the treatment of chronic osteomyelitis. A
      case report.

PMID- 15741633
TI  - Fresh-frozen osteochondral allograft reconstruction of a severely fractured
      talus. A case report.

PMID- 15741634
TI  - Reconstruction of a neglected posterior dislocation of the shoulder through a
      limited posterior deltoid-splitting approach. A case report.

PMID- 15741635
TI  - Capitellar fracture in a child: the value of an oblique radiograph. A case
      report.

PMID- 15741636
TI  - Posterior shoulder dislocations and fracture-dislocations.
AB  - Posterior shoulder dislocations and fracture-dislocations are uncommon injuries
      that most often occur during seizures or as a result of high-energy trauma.
      Despite advances in imaging, they are frequently diagnosed late. Detection is
      facilitated by heightened clinical suspicion of the injury in high-risk
      individuals together with appropriate radiographic investigation. A wide variety
      of operative techniques, ranging from simple closed reduction to soft-tissue and
      bone stabilization procedures to prosthetic arthroplasty, are available to treat
      these injuries. Selection of the most appropriate treatment option is complex and
      multifactorial. Because of the rarity of these injuries, evidence-based treatment
      protocols are difficult to devise. Good functional outcomes are associated with
      early detection and treatment of isolated posterior dislocations that are
      associated with a small osseous defect and are stable following closed reduction.
      Poor prognostic factors include late diagnosis, a large anterior defect in the
      humeral head, deformity or arthrosis of the humeral head, an associated fracture
      of the proximal part of the humerus, and the need for an arthroplasty.

PMID- 15741637
TI  - Symposium. Operative treatment of patellofemoral arthritis.

PMID- 15741638
TI  - Repair of bone in the presence of aseptic necrosis resulting from fractures,
      transplantations, and vascular obstruction. 1930.

PMID- 15741639
TI  - Clarifying the presence of posttraumatic stress symptoms following orthopaedic
      trauma.

PMID- 15741640
TI  - Comparison of primary total hip replacements performed with a standard incision
      or a mini-incision.

PMID- 15741641
TI  - Estimating the risk of nonunion following nonoperative treatment of a clavicular
      fracture.

PMID- 15741642
TI  - Idiopathic arm pain.

PMID- 15741643
TI  - The least publishable unit.

PMID- 15741644
TI  - Shock-wave therapy for plantar fasciitis.

PMID- 15741645
TI  - Thirty-day mortality following hip arthroplasty.

PMID- 15741647
TI  - Objectives of undergraduate medical education in musculoskeletal surgery and
      medicine.

PMID- 15741648
TI  - What's new in sports medicine.

PMID- 15741649
TI  - Crossing the barrier: net flux of 27-hydroxycholesterol into the human brain.
AB  - Side chain oxidized oxysterols have a unique ability to traverse lipophilic
      membranes. We tested the hypothesis that there is a net flux of 27
      hydroxycholesterol from the circulation into the brain using plasma samples
      collected from the internal jugular vein and an artery of healthy male
      volunteers. Two independent studies were performed, one in which total levels of
      27-hydroxycholesterol were measured and one in which the free fraction of 27
      hydroxycholesterol was measured. In the majority of subjects studied, the level
      of 27-hydroxycholesterol was higher in the artery than in the vein, and uptake
      from the circulation was calculated to be about 5 mg/24 h. The distribution of 27
      hydroxycholesterol in human brain was found to be consistent with an
      extracerebral origin, with a concentration gradient from the white to the gray
      matter--a situation opposite that of 24S-hydroxycholesterol, which os exclusively
      formed in brain. In view of the fact that the blood-brain barrier is impermeable
      to cholesterol and that 27-hydroxycholesterol is a potent regulator of several
      cholesterol-sensitive genes, the flux of 27-hydroxycholesterol into the brain may
      be and important link between intra- and extracerebral cholesterol homeostasis.

PMID- 15741650
TI  - ESI-MS quantitation of increased sphingomyelin in Niemann-Pick disease type B
      HDL.
AB  - HDLs have been proposed to have antiatherogenic properties because of their role
      in reverse cholesterol transport as lipid acceptors. To elucidate the
      phospholipid profile of these particles, we used electrospray ionization mass
      spectrometry to examine the phosphatidylcholine (PC) and sphingomyelin (SM)
      composition of HDLs purified from plasma and nascently generated in vitro from
      fibroblasts. We also quantitatively compared the phospholipids present in these
      lipoproteins between normal and Niemann-Pick disease type B (NPD-B) subjects
      characterized by sphingomyelinase (SMase) deficiency. We demonstrated that plasma
      HDLs from NPD-B were significantly enriched in SM by an average of 28%,
      particularly the palmitoyl SM (with an increase of 95%), which accounted for
      approximately 25-44% of total SM molecular species. Similarly, we observed an
      increase of approximately 63% in total SM levels in nascent HDLs prepared from
      NPD-B fibroblasts. Although PC levels in nascent HDLs were comparable between
      control and NPD-B cells, there was a 95% increase in total PC levels similar to
      that of SM in plasma HDLs extracted from NPD-B subjects. These data provide
      insight into the structure of HDLs and identify potential new roles for SMase in
      lipoprotein metabolism.

PMID- 15741652
TI  - Biliary cholesterol crystallization characterized by single-crystal cryogenic
      electron diffraction.
AB  - Cholesterol crystals are the building blocks of cholesterol gallstones. The exact
      structure of early-forming crystals is still controversial. We combined cryogenic
      temperature transmission electron microscopy with cryogenic-temperature electron
      diffraction to sequentially study crystal development and structure in nucleating
      model and native gallbladder biles. The growth and long-term stability of classic
      cholesterol monohydrate (ChM) crystals in native and model biles was determined.
      In solutions of model bile with low phospholipid-to-cholesterol ratio, electron
      diffraction provided direct proof of a novel transient polymorph that had an
      elongated habit and unit cell parameters differing from those of classic
      triclinic ChM. This crystal is exactly the monoclinic ChM phase described by
      Solomonov and coworkers (Biophysical J., In press) in cholesterol monolayers
      compressed on the air-water interface. We observed no evidence of anhydrous
      cholesterol crystallization in any of the biles studied. In conclusion, classic
      ChM is the predominant and stable form in native and model biles. However, under
      certain (low phospholipid) conditions, transient intermediate polymorphs may
      form. These findings, documenting single-crystal analysis in bulk solution,
      provide an experimental approach to investigating factors influencing biliary
      cholesterol crystal nucleation and growth as well as other processes of
      nucleation and crystallization in liquid systems.

PMID- 15741651
TI  - Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role
      of fatty acid beta-oxidation and glucose.
AB  - Mitochondrial cytopathy has been associated with modifications of lipid
      metabolism in various situations, such as the acquisition of an abnormal
      adipocyte phenotype observed in multiple symmetrical lipomatosis or triglyceride
      (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged
      red fibers syndrome. However, the molecular signaling leading to fat metabolism
      dysregulation in cells with impaired mitochondrial activity is still poorly
      understood. Here, we found that preadipocytes incubated with inhibitors of
      mitochondrial respiration such as antimycin A (AA) accumulate TG vesicles but do
      not acquire specific markers of adipocytes. Although the uptake of TG precursors
      is not stimulated in 3T3-L1 cells with impaired mitochondrial activity, we found
      a strong stimulation of glucose uptake in AA-treated cells mediated by calcium
      and phosphatidylinositol 3-kinase/Akt1/glycogen synthase kinase 3beta, a pathway
      known to trigger the translocation of glucose transporter 4 to the plasma
      membrane in response to insulin. TG accumulation in AA-treated cells is mediated
      by a reduced peroxisome proliferator-activated receptor gamma activity that
      downregulates muscle carnitine palmitoyl transferase-1 expression and fatty acid
      beta-oxidation, and by a direct conversion of glucose into TGs accompanied by the
      activation of carbohydrate-responsive element binding protein, a lipogenic
      transcription factor. Taken together, these results could explain how
      mitochondrial impairment leads to the multivesicular phenotype found in some
      mitochondria-originating diseases associated with a dysfunction in fat
      metabolism.

PMID- 15741653
TI  - Hypolipidemic action of the SERM acolbifene is associated with decreased liver
      MTP and increased SR-BI and LDL receptors.
AB  - This study aimed to identify the mechanisms of the hypolipidemic action of the
      selective estrogen receptor modulator (SERM) acolbifene (ACOL). Four weeks of
      treatment with ACOL reduced fasting and postprandial plasma triglycerides (TGs),
      an effect associated with lower VLDL-TG secretion rate (-25%), and decreased mRNA
      of microsomal triglyceride transfer protein (MTP; -29%). ACOL increased liver TG
      concentration (+100%) and amplified the feeding-induced increase in the master
      lipogenic regulators sterol-regulatory element binding protein-1a (SREBP-1a) and
      SREBP-1c. ACOL decreased total, HDL, and non-HDL cholesterol (CHOL) by 50%. SREBP
      2 mRNA and HMG-CoA reductase activity were minimally affected by ACOL. However,
      in the fasted state, liver concentration of scavenger receptor class B type I (SR
      BI) protein, but not mRNA, was 3-fold higher in ACOL-treated than in control
      animals and correlated with plasma HDL-CHOL levels (r = 0.80, P < 0.002). Liver
      LDL receptor (LDLR) protein, but not mRNA, was increased 2-fold by ACOL,
      independently of the nutritional status. This study demonstrates that ACOL
      possesses the unique ability among SERMs to reduce VLDL-TG secretion, likely by
      reducing MTP expression, and strongly suggests that the robust
      hypocholesterolemic action of ACOL is related to increased removal of CHOL from
      the circulation as a consequence of enhanced liver SR-BI and LDLR abundance.

PMID- 15741655
TI  - Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and
      late-pregnant rats.
AB  - Untreated maternal hypothyroidism (hypoT) has serious consequences in offspring
      development that may result from the effect on lactation of maternal metabolism
      dysfunction. We studied the effects of prolonged propylthiouracil (PTU)-induced
      hypoT (0.1% PTU in drinking water starting 8 days before mating until day 21 of
      pregnancy or for 30 days in virgin rats) on liver and mammary lipid metabolism
      and serum lipid concentrations. In virgins, hypoT reduced hepatic mRNAs
      associated with triglyceride (TG) and cholesterol synthesis (including fatty acid
      synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase), and induced
      lobuloalveolar mammary development. Pregnancy increased hepatic mRNAs associated
      with TG and cholesterol synthesis and uptake (including LDL receptor) and with
      lipid oxidation, such as acyl CoA oxidase. HypoT decreased mRNAs and the activity
      of proteins associated with TG synthesis, and mRNAs associated with cholesterol
      uptake and lipid oxidation. Pregnancy increased mammary mRNAs related to lipid
      oxidation and decreased cholesterol synthesis, whereas hypoT decreased mRNAs and
      activities of proteins associated with TG synthesis and decreased epithelial
      mammary tissue. Virgin and pregnant hypoT rats had increased circulating VLDL +
      LDL cholesterol. HypoT decreased circulating TGs in pregnant rats. The observed
      effects of hypoT may result in decreased mammary lipid availability. This, along
      with the decreased epithelial mammary tissue during lactogenesis, may contribute
      to the future lactational deficit of hypoT mothers.

PMID- 15741654
TI  - Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing
      lipoprotein production in mouse and cultured cells.
AB  - Mutations in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) have been
      associated with autosomal dominant hypercholesterolemia. In vivo kinetic studies
      indicate that LDL catabolism was impaired and apolipoprotein B (apoB)-containing
      lipoprotein synthesis was enhanced in two patients presenting with the S127R
      mutation on PCSK9. To understand the physiological role of PCSK9, we
      overexpressed human PCSK9 in mouse and cellular models as well as attenuated the
      endogenous expression of PCSK9 in HuH7 hepatoma cells using RNA interference.
      Here, we show that PCSK9 dramatically impairs the expression of the low density
      lipoprotein receptor (LDLr) and, in turn, LDL cellular binding as well as LDL
      clearance from the plasma compartment in C57BL6/J mice but not in LDLr-deficient
      mice, establishing a definitive role for PCSK9 in the modulation of the LDLr
      metabolic pathway. In contrast to data obtained in S127R-PCSK9 patients
      presenting with increased apoB production, our study indicates that wild-type
      PCSK9 does not significantly alter the production and/or secretion of VLDL apoB
      in either cultured cells or mice. Finally, we show that unlike PCSK9
      overexpression in mice, the S127R mutation in patients led to increased VLDL apoB
      levels, suggesting a potential gain of function for S127R-PCSK9 in humans.

PMID- 15741656
TI  - PAT family proteins pervade lipid droplet cores.
AB  - The PAT family proteins, named after perilipin, adipophilin, and the tail
      interacting protein of 47 kDa (TIP47), are implicated in intracellular lipid
      metabolism. They associate with lipid droplets, but how is completely unclear.
      From immunofluorescence studies, they are reported to be restricted to the outer
      membrane monolayer enveloping the lipid droplet and not to enter the core.
      Recently, we found another kind of lipid droplet-associated protein, caveolin-1,
      inside lipid droplets. Using freeze-fracture immunocytochemistry and electron
      microscopy, we now describe the distributions of perilipin and caveolin-1 and of
      adipophilin and TIP47 in lipid droplets of adipocytes and macrophages. All of
      these lipid droplet-associated proteins pervade the lipid droplet core and hence
      are not restricted to the droplet surface. Moreover, lipid droplets are
      surprisingly heterogeneous with respect to their complements and their
      distribution of lipid droplet-associated proteins. Whereas caveolin-1 is
      synthesized in the endoplasmic reticulum and is transferred to the lipid droplet
      core by inundating lipids during droplet budding, the PAT proteins, which are
      synthesized on free ribosomes in the cytoplasm, evidently target to the lipid
      droplet after it has formed. How the polar lipid droplet-associated proteins are
      accommodated among the essentially hydrophobic neutral lipids of the lipid
      droplet core remains to be determined.

PMID- 15741658
TI  - Microsatellite DNA polymorphism divergence in Chinese wheat (Triticum aestivum
      L.) landraces highly resistant to Fusarium head blight.
AB  - Genetic differences between 20 Chinese wheat (Triticum aestivum L.) landraces
      highly resistant to Fusarium head blight (FHB) and 4 wheat lines highly
      susceptible to FHB were evaluated by means of microsatellite markers, in order to
      select suitable parents for gene mapping studies. Thirty-nine out of 40
      microsatellite markers (97.5%) were polymorphic among the 24 wheat genotypes. A
      total of 276 alleles were detected at the 40 microsatellite loci. The number of
      alleles per locus ranged from 1 to 16, with an average of 6.9 alleles. Among
      these microsatellite loci, the largest polymorphism information content (PIC)
      value was 0.914 (GWM484), while the lowest PIC value was 0 (GWM24). The mean
      genetic similarity index among the 24 genotypes was 0.419, ranging from 0.103 to
      0.673. Clustering analysis indicated that the highly susceptible synthetic wheat
      line RSP was less genetically related to and more divergent from the Chinese
      highly resistant landraces. These results were useful in the identification of
      suitable parents for the development of mapping populations for tagging the FHB
      resistance genes among these Chinese wheat landraces.

PMID- 15741659
TI  - Cytology and fertility of viable hybrids of Nicotiana tabacum L. cv. TB-566 with
      N. alata Link et Otto.
AB  - A vigorous hybrid (N. tabacum cv. TB-566 tetra x N. alata) x N. alata was
      obtained by backcrossing a partly viable sesquidiploid hybrid N. tabacum cv. TB
      566 tetra x N. alata to N. alata. The hybrid was a 35-chromosome near
      amphihaploid with a pair of N. alata chromosomes in disomic condition. It was
      completely self- and cross-sterile and formed from 7 to 8 bivalents in pollen
      mother cells. By using stem pith culture, polyploidized regenerants were obtained
      from the 35-chromosome hybrid with somatic chromosome numbers from 65 to 70.
      These regenerants showed fairly regular meiosis with the number of bivalents in
      pollen mother cells ranging from 27.3 to 30.4. Irregularities in meiosis included
      a high number of univalents, aberrant tetrads, and a high frequency of
      micronuclei. The percentage of acetocarmine-stainable pollen ranged from 22.1 to
      78.4. A 66-chromosome regenerant showed fairly regular meiosis and was self
      fertile but could not be backcrossed to N. tabacum. This barrier seems to be
      caused by genic imbalance rather than irregularities of meiotic divisions. Hence
      transfer programs based on the introgression of entire linkage groups (sexual and
      somatic hybridization) seem to be of little use in the case of that species.

PMID- 15741660
TI  - Induction and characterization of streptomycin-resistant mutants in Capsicum
      praetermissum.
AB  - Streptomycin-resistant mutants were isolated from mutagenised cotyledon explants
      of Capsicum praetermissum Heiser & Smith. The explants were mutagenised with N
      ethyl-N-nitrosourea, which resulted in a high frequency of streptomycin-resistant
      mutants (18.0%) and a low frequency of chlorophyll-deficient (albino) mutants
      (8.0%). Complete streptomycin-resistant plantlets were obtained after rooting of
      the regenerated green shoots on rooting medium containing 1.0 mg L-1 IAA and 500
      mg L-1 streptomycin sulphate. Leaf-segment assay of these plantlets revealed that
      they were resistant to streptomycin but sensitive to chloramphenicol, kanamycin,
      lincomycin, and spectinomycin. Reciprocal crosses between streptomycin-resistant
      and -sensitive plants showed a non-Mendelian transmission of resistance by female
      parents.

PMID- 15741661
TI  - Diversity of diploid androgenic Brussels sprout plants of R0 and R1 generations.
AB  - Androgenic Brussels sprout plants were produced by the use of anther culture from
      the donor cultivar 'Philemon F1'. A total of 96 plants obtained from 20
      androgenic R0 genotypes assigned as diploids were evaluated both in the
      generative and vegetative stage, in respect of their morphological characters:
      mean plant height; leaf size, colour and waxiness; leaf blade shape, blistering
      and attitude; number of sprouts; as well as their self-incompatibility and
      fertility. Androgenic R0 plants derived from each of the 20 embryos were highly
      diversified and differed from the donor in one or more morphological traits in
      the vegetative stage. Evaluated populations also varied in fertility and self
      incompatibility. Six androgenic genotypes that set a sufficient amount of seeds
      of the R1 generation and 'Philemon F1' were evaluated in the field in respect of
      plant height, total and marketable yield per plot, shape of stem with sprouts,
      shape and density of sprouts, and spacing between sprouts. Only four diploid R0
      and R1 populations may have some value for further breeding, as they are
      characterised by good vigour, high or medium ability for sprout generation, and
      sufficient fertility.

PMID- 15741662
TI  - Resistance of cultivars and breeding lines of spring wheat to Fusarium culmorum
      and powdery mildew.
AB  - Twelve Polish spring wheat cultivars and 18 spring wheat accessions from CIMMYT,
      Mexico, were examined for resistance to a highly pathogenic Fusarium culmorum
      strain KF846 and powdery mildew in 5-year field experiments. Resistant wheat
      cultivars (Sumai 3 and Frontana) served as controls. The mean percentage of
      Fusarium-damaged kernels (% FDK) for 5 years was lower in CIMMYT accessions
      (16.7%) than in Polish spring cultivars (28.3%). In all Polish spring cultivars,
      % FDK was higher than in the control cultivars Sumai 3 and Frontana (12-20%). The
      mean disease score (on a scale of 1-9) for powdery mildew (natural infection) for
      all examined cultivars and lines ranged from 0 to 7 and in the Polish spring
      cultivars was significantly lower (0-5). Cultivars Eta, Henika, Ismena, Jasna and
      Olimpia were found to be the least susceptible to powdery mildew in field
      experiments. The laboratory host-pathogen tests with Blumeria graminis f. sp.
      tritici isolates showed that only two cultivars were characterized by identical
      resistance patterns as the standard differential lines with documented resistance
      genes. Cultivar Alkora had the gene Pm3d, and Henika had Pm5. The gene Pm3d was
      identified in cultivars Jasna and Eta in combination with another unknown
      gene/genes. Cultivars Santa and Torka had the gene Pm5 in combination with
      another unknown gene/genes. Four cultivars: Banti, Ismena, Olimpia and Sigma,
      showed resistance to all mildew isolates employed in a laboratory test. The
      accession IPG-SW-14 was the least susceptible to both pathogens (F. culmorum and
      powdery mildew) in all 5 years of experiments. This line is the best candidate
      for deriving new cultivars with improved resistance to fungal diseases.

PMID- 15741663
TI  - Reciprocal controlled crosses between Pinus sylvestris and P. mugo verified by a
      species-specific cpDNA marker.
AB  - A species-specific marker of cpDNA (paternally inherited in pines) was used to
      verify the hybrid origin of seedlings from controlled reciprocal crosses between
      Pinus sylvestris and P. mugo. A very low degree of compatibility between those
      two species has been revealed. In the three consecutive years of experiments, no
      filled seeds were obtained in the combination with P. mugo as the seed parent.
      From P. sylvestris as the seed parent and P. mugo as the pollen donor, we
      succeeded to obtain four filled seeds (about 1 %), but only in one year. The
      seedling obtained from the seeds had cpDNA haplotypes specific to P. mugo, which
      proves their hybrid origin. This method enables verification of the result of
      controlled crosses. The importance of the results has been discussed in the
      aspect of postulated natural hybridisation in sympatric populations of the two
      species.

PMID- 15741664
TI  - MilkProtChip--a microarray of SNPs in candidate genes associated with milk
      protein biosynthesis--development and validation.
AB  - MilkProtChip is an oligonucleotide microarray based on the arrayed primer
      extension (APEX) technique, allowing genotyping of single nucleotide
      polymorphisms (SNPs) in genes of interest for bovine milk protein biosynthesis.
      APEX consists of a sequencing reaction primed by an oligonucleotide anchored with
      its 5'end to a glass slide and terminating one nucleotide before the polymorphic
      site. The extension with one fluorescently labeled dideoxy nucleotide
      complementary to the template reveals the polymorphism. A total of 75 SNPs were
      selected among those associated directly or potentially with milk protein
      content. Among the 75 SNPs, 4 did not produce a positive signal. Most of the
      remaining SNPs produced a signal for both strands, except for 4 (one strand). In
      the validation step, 12 Polish Holstein bulls, 1 Polish Red bull, 1 bison (Bison
      bonasus), 11 Jersey cows and 25 Polish Holstein cows were screened to validate
      SNPs. Among the 71 selected SNPs--26 were found monoallelic, the rest showing at
      least two genotypes for the entire population under study. All the animals were
      earlier genotyped for 2-5 SNPs by PCR-RFLP and PCR sequencing and all showed
      complete concordance with APEX genotyping. APEX reactions showed relatively high
      signal frequencies: more than 0.9, 0.9-0.8 and below 0.8, for 65, 4 and 2 DNA
      samples, respectively. The primary application of the MilkProtChip is the
      simultaneous genotyping of dozens of SNPs to reveal and clarify the genetic
      background of milk protein biosynthesis. The chip may possibly be used for dairy
      cattle identification and paternity analysis, evolutionary studies, the
      evaluation of genetic distances between wild and domestic cattle breeds and the
      domestication history of bovine species.

PMID- 15741665
TI  - Leukocyte acid phosphatase and metabolic efficiency of phagocytes in the first
      lactation trimester of cows from a leukaemic herd.
AB  - In Black-and-White cattle, polymorphism of acid phosphatase (AcP) of blood
      leukocytes is determined by a pair of autosomal alleles. The aim of the study was
      to determine the relationship between AcP polymorphism and the metabolic
      efficiency of phagocytes in the first months after calving of cows naturally
      infected with the bovine leukaemia virus. The studied population consisted of 91
      Black-and-White cows aged 3-6 years, from one herd. Enzootic bovine leukaemia
      (EBL) was diagnosed with the immuno-enzymatic ELISA method and a PCR molecular
      test. Additionally, agarose gel electrophoresis and the cytochemical method were
      used to determine the AcP polymorphism and activity in leukocytes. The metabolic
      activity of phagocytes was determined by the nitroblue tetrazolium (NBT)
      reduction test. Significant differences in metabolic efficiency of granulocytes
      were observed between cows representing different AcP phenotypes. No significant
      differences in levels of the analysed indices were observed between the EBL
      positive and EBL-negative cows and between the three subsequent months after
      calving.

PMID- 15741666
TI  - Identification of gadoid species (Pisces, Gadidae) by PCR-RFLP analysis.
AB  - A rapid PCR-RFLP analysis was optimized to identify the presence of 3 closely
      related gadoid fish species: Alaska pollack Theragra chalcogramma, Pacific cod
      Gadus macrocephalus and Atlantic cod Gadus morhua in commercial seafood products.
      Gadoid universal primers were designed for PCR amplification of a 558-bp fragment
      encoding the mitochondrial cytochrome b gene. Without purification of the PCR
      products, double digestion with Eco32I and Eco105I restriction enzymes generated
      reproducible species-specific restriction patterns visualizing 3 fragments (106
      bp, 161 bp and 291 bp) in Alaska pollack and 2 fragments (106 bp and 452 bp) in
      Pacific cod, whereas no cleavage was observed in Atlantic cod. This PCR-RFLP
      analysis is simple, rapid and reliable, and therefore can be routinely applied to
      discover fraudulent substitution among 3 economically important gadoid species in
      commercial seafood products.

PMID- 15741667
TI  - Isolation, cloning and expression of DNA fragments reflecting open reading frames
      of 1.8 and 4.6 kb RNAs of the I-18 C gene of Chironomus tentans.
AB  - This study, based on the genetic engineering approach, concerns the regulation of
      the insect gene expression, but it has also a strong significance for plant
      protection, which is associated with the future possibility to control insect
      development more effectively, especially in those species that are pests of
      cultivated plants. The I-18 C gene of Chironomus tentans is activated by heat
      shock and the steroid hormone--ecdysone. This gene produces different transcripts
      (at least four) by alternative splicing. Two different open reading frames, i.e.
      ORFs I and II of the two main transcripts of this gene, i.e. the 1.8 and 4.6 kb
      RNA, had been isolated, at the DNA level, as the ORFs reflecting DNA fragments,
      using the polymerase chain reaction, then were cloned into the bluescript vector
      and finally were cloned into the pET-3a vector to be translated in the T7 RNA
      polymerase/promoter system of E. coli. As the preliminary outcome of these
      experiments it was possible to obtain ORF I overexpressed as the polypeptide,
      whereas ORF II was expressed as the polypeptide that was strongly visible on SDS
      polyacrylamide gel. This could facilitate further studies regarding the
      mechanisms of expression of this gene, including the level of expression of this
      gene during the C. tentans development.

PMID- 15741668
TI  - DGAT1 K232A quantitative trait nucleotide polymorphism in Polish Black-and-White
      cattle.
AB  - The diacylglycerol o-acyltransferase 1 gene (DGAT1) was investigated in Polish
      Black-and-White cattle. The frequency of the K allele was 0.60, 0.68 and 0.48 for
      AI sires (n=150), young bulls (n=139) and cows (n=213), respectively. The method
      of selective genotyping for identification of the quantitative trait nucleotide
      was verified through identification of DGAT1 effect on milk production traits.
      Daughters of six heterozygous bulls were selectively genotyped based on their
      milk traits. The genotypic frequencies differed between high and low yield groups
      representing milk and fat contents. The Kruskal-Wallis test revealed a highly
      significant effect of DGAT1 K232A in cows with extremely low fat content and a
      significant effect in cows with extremely high protein content of milk. No
      significant effect of AI sires' genotypes on their breeding value was found.

PMID- 15741669
TI  - Genetic variability among Polish Red, Hereford and Holstein-Friesian cattle
      raised in Poland based on analysis of microsatellite DNA sequences.
AB  - Polymorphism of 11 microsatellite DNA loci was analysed in Polish Red (PR),
      Hereford and Holstein-Friesian (HF) cattle raised in Poland and genetic distance
      among these breeds was determined. At the 11 loci (TGLA227, BM2113, TGLA53,
      ETH10, SPS115, TGLA126, TGLA122, INRA23, ETH3, ETH225 and BM1824) analysed with
      automated DNA sizing technology, a total of 213 alleles were identified: 76 in
      PR, 76 in HF, and 61 in Hereford. All the microsatellite DNA markers showed high
      polymorphism. Polymorphism information content (PIC) calculated for each marker
      exceeded 0.5, except for the ETH3 locus in Hereford cattle (PIC=0.475), and
      heterozygosity (H) ranged from 54.1% to as much as 85.2%. The coefficient of
      genetic distance was 0.354 between PR and Hereford, 0.414 between HF and
      Hereford, and 0.416 between PR and HF cattle.

PMID- 15741670
TI  - A review of asthma genetics: gene expression studies and recent candidates.
AB  - Recent evidence indicates an important role of inflammation pathways, airways
      remodeling and epithelium activation in asthma genetics. In particular,
      transcriptome studies have detected differentially expressed genes involved in
      eosinophil apoptosis, the arginase pathway, response to allergens or
      interleukins, and to inhaled corticosteroids. Candidate gene and genome wide
      studies have localized genetic regions involved in the disease, such as the A1AR
      and CLCA1 genes (chromosome 1), IL-1RN and DPP10 (2q14), HLA-G and TNF-a (6p21),
      GPRA (7p14), FceRI and GSTP1 (11q13), NOS1, IFNG, STAT6, VDR, and other genes
      (12q13-26), PHF11 and flanking genes (13q14), AACT and PTGDR (14q), and ADAM33
      (20p13). The role of these and other genetic determinants has to be confirmed in
      future, preferably longitudinal, studies.

PMID- 15741671
TI  - Molecular findings in Brazilian patients with osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a genetic disorder of increased bone fragility
      and low bone mass. Severity varies widely, ranging from intrauterine fractures
      and perinatal lethality to very mild forms without fractures. Most patients with
      a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes that
      encode the a chains of type I procollagen, the major protein in bones. Hence, the
      aim of the present study was to identify mutations in the COL1A1 gene in 13
      unrelated Brazilian OI patients. This is the first molecular study of OI in
      Brazil. We found 6 mutations, 4 of them novel (c.1885delG, p.P239A, p.G592S,
      p.G649D) and 2 previously described (p.R237X and p.G382S). Thus, the findings
      show that there are no prevalent mutations in our sample, and that their
      distribution is similar to that reported by other authors, with preponderance of
      substitutions for glycine in the triple helix domain, causing OI types II, III
      and IV.

PMID- 15741672
TI  - Recombination aneusomy of subtelomeric regions of chromosome 5, resulting from a
      large familial pericentric inversion inv(5)(p15.33q35.3).
AB  - We present a family with three cases of recombination aneusomy rec(5)dup(5q)
      originating from a large parental pericentric inversion of chromosome 5. The
      proband--a 6-year-old girl with mental retardation, speech delay, microcephaly,
      and slight facial dysmorphism--was referred for subtelomere testing. FISH with a
      Multiprobe Chromoprobe T System (CytoCell) and with several BAC clones mapping to
      both subtelomere regions of chromosome 5, revealed a recombinant chromosome
      rec(5)dup(5q) originating from a paternal pericentric inversion
      inv(5)(p15.33q35.3). The same inversion was present in the proband's father's
      twin-brother and rec(5)dup(5q) was also identified in his two mentally retarded
      daughters. The distance of breakpoints from the telomere was: 0.234-1.4 Mb for 5p
      and 4.1-4.8 Mb for 5q. HR-CGH analysis confirmed the duplication of the 5q
      subtelomeric region but did not identify any concomitant deletion in the 5p
      subtelomere. Precise mapping of the aneusomic regions in the proband enabled
      mapping the cat cry and speech delay to 5p15.33, making the earlier localizations
      of these features more precise. Our family shows that the large pericentric
      inversion with both breakpoints at subtelomeric regions of chromosome 5 is
      associated with a high risk of rec(5)dup(5q) in the progeny.

PMID- 15741673
TI  - [Indication and significance of pharmacological intervention for back pain].
AB  - Back pain is divided into two phases; acute pain is due to the increased signal
      from the nociceptive receptors in the nerve endings and chronic pain is resulting
      from the reconstruction of the new nervous net work during the healing stage. Use
      of NSAIDs and opioids is indicated for the acute pain that is not eased by taking
      a rest. NSAIDs is also profitable to control chronic pain, but NSAIDs has
      complications of renal and digestive functions. Persons with ages of more than 65
      are especially liable to those dysfunctions. Pharmacological intervention on back
      pain may not only give the therapeutic benefits but also it can provide the clues
      for the elucidation of the mechanism and the new therapeutic interventions.

PMID- 15741674
TI  - [The indication and clinical value of neural blocks for low back pain].
AB  - Neural blocks are commonly used for patients with acute or chronic low back pain.
      It is important to do correctly technical procedure of neural blocks and more
      important to be well aware of the indication and clinical value of neural blocks.
      Neural blocks have two aspects of diagnostic and therapeutic value. In this
      article, the indication and clinical value of neural blocks were reviewed in
      trigger point blocks, epidural blocks, selective nerve root blocks, facet blocks
      and lumbar posterior medial branch blocks.

PMID- 15741675
TI  - [Surgical management for low back pain. Rationale and indication].
AB  - Various spinal diseases that cause low back pain have two distinct pathologies,
      including mechanical disruption of the spinal column and compression of the cauda
      equina and the nerve roots. Although, the advancement in surgical techniques has
      brought satisfactory neural recovery, resolution of low back pain still remains
      unpredictable. The development of low back pain is affected by psychosocial
      factors besides pathological lesions in the lumbar spine leading to functional
      impairment. Surgical indication for low back should be carefully decided
      considering such nonorganic aspects of low back pain.

PMID- 15741676
TI  - [Epidemiology of low back pain].
AB  - Epidemiology of low back pain, that is, the study of the incidence and prevalence
      of the pain is essential for detecting the degree of time and physical loss in a
      person or a society, and for making a project to minimize the loss. For carrying
      out the study, definition of low back pain is important to understand correctly
      the real state and comparing the variable data resulting from different studies.

PMID- 15741677
TI  - [Clinical anatomy of lumbar spine].
AB  - Three elements contribute to the neurologic symptoms of the lumbar spine or its
      multiplicity from an anatomical viewpoint. The first element is the problem of
      neural tissue. The second element is the bone or the soft tissue existing around
      the circumference of the neural tissue. The third element is the correlation of
      the above two. In other words, the neural tissue as content is too large or the
      adjacent tissue as container is too narrow or else an aberration in the
      correlation of the aforesaid is involved. Therefore, it is necessary to study
      those three elements to comprehend the neurologic symptoms of the lumbar spine.

PMID- 15741678
TI  - [The basic research of lumbar herniated disc].
AB  - Various genes are reported as one of a key gene for lumbar intervertebral disc
      degeneration. The cross-talk between inflammatory cells and disc cells results in
      generation of many inflammatory cytokines, growth factors, and proteinases. In
      near future, a new strategy for the treatment of disc degeneration and herniated
      disc should be developed based on current evidences.

PMID- 15741679
TI  - [Experimental studies of lumbar spinal stenosis].
AB  - Neurophysiologic function and ischemia causes neurogenic symptoms in lumbar
      spinal stenosis. Neurophysiologic function and potential therapeutic agents were
      investigated using a chronic cauda equina compression model that was developed
      according to a clinical pathogenesis. In the chronic cauda equina compression
      model, nerve conduction velocity and blood flow in spinal nerves decreased but
      mechanical allodynia was not induced. Prostaglandins and 5-HT receptor antagonist
      effected to improve blood flow in nerve roots after cauda equina
      compression;therefore, they might be potential agents for lumbar spinal stenosis.

PMID- 15741680
TI  - [Pathophysiology of radicular pain].
AB  - Pathophysiological mechanisms of low back pain and radicular pain produced by
      lumbar disorders are still controversial. We have made experimental animal models
      and have elucidated the mechanisms of hyperalgesia, which is a pain related
      behavior, in these animals. We have not demonstrated that only mechanical
      compression of the nerve roots in the lumbar spine results in hyperalgesia in
      rat. We found that application of the nucleus pulposus to the nerve roots
      produces time-dependent reversible hyperalgesia in the affected hindpaw of the
      rat, and that the hyperalgesia is related to bioactive substances in the
      arachidonic acid cascade. We have also reported that inflammatory granulation
      tissue around the nerve root is related to hyperalgesia rather than the nucleus
      pulposus itself, and that mechanical compression to the nerve root after
      application of the nucleus pulposus produces different type of hyperalgesia.
      Collectively, not only mechanical compression of the cauda equina and nerve root
      but also various inflammatory substances are related to pathophysiological
      mechanisms of radicular pain in patients with lumbar disorders such as disc
      herniation. Elucidating pathophysiological mechanisms of pain-related behaviors
      such as hyperalgesia is important to establish a new strategy for the treatment
      of lumbar painful radiculopathy.

PMID- 15741681
TI  - [Blood circulation of cauda equina and nerve root].
AB  - It is generally considered that the genesis of radiculopathy associated with
      pathologic conditions of the spine, such as lumbar disc herniaton and lumbarl
      canal stenosis, may result from both mechanical compression and vascular
      problems. In this article, we have reviewed about the blood circulation of cauda
      equina and nerve root under normal and pathologic conditions.

PMID- 15741682
TI  - [Evaluation of low back pain].
AB  - Patients with low back pain should be evaluated on their various clinical
      aspects. The evaluation instruments can be classified into four types: pain
      measures, function measures, psychosocial measures, and composite measures. The
      evaluation should be done by patient self-reporting style. Since it is difficult
      to evaluate patients with a single measure, the evaluation should be done with
      combination of several instruments.

PMID- 15741683
TI  - [Biological approach for treatment of degenerative disc diseases].
AB  - Intervertebral disc degeneration and associated spinal disorders including low
      back pain are a leading source of morbidity and a major cause of work disability
      as well as increased health care costs. Recent advance of molecular biology
      enable us to utilize these new techniques for understanding disc cell function
      and mechanisms of disc degeneration. Furthermore, these new technology may open
      novel therapeutic strategy such as application of growth factors, stem cell
      therapy, and gene therapy to regenerate degenerated intervertebral discs.

PMID- 15741684
TI  - [Clinical evaluation of low back pain].
AB  - On the diagnosis of backache, at first ask patients detailed questions about
      medical history of backache, the situation at the time of onset and process of
      the pain, intensity and location on the body of the pain, which movement to
      strengthen them or which posture to moderate them. Following them, check the
      abnormality of how to walk and the normal curvature of the spine at standing from
      behind and the side. Examine the movement and flexibility of the lumbar spine in
      bending forward, backward and twisting. After them, examine the neurological
      functions on their legs to search paralysis, muscle weakness, reflex changes and
      sensory changes. Observe lumbar part and check the presence of redness, swelling
      and hyperthermia, and examine a location of tenderness. X-rays, CT or MRI
      examination can be performed if necessary, but should not be fascinated by only
      image findings, and it is necessary to evaluate in total them with the results of
      physical examinations.

PMID- 15741685
TI  - [Minimally invasive surgical approach for the low back pain].
AB  - The fact that minimally invasive surgery for the low back pain is considerably
      less traumatic has been documented by two broad categories consisted of
      intradiscal therapeutic and endoscopic procedures. A marked reduction in length
      of hospitalization has been noted in many cases. Surgeons should select the
      procedure, or combination of procedures, best suited to benefit of the patient.

PMID- 15741686
TI  - [Liaison-psychiatric approach for patients with chronic low back pain].
AB  - There are a number of chronic low back pain patients who have not only the
      somatic disorder as disability of the trunk but also the mental disorder, i.e.
      insomnia, depression. It should pay attention to the mental state of the patients
      and human relationship in home and career, as background of low back pain.
      Liaison-Psychiatric Approach means that orthopedist works in cooperation with
      psychiatrist. Medical team including orthopedist, psychiatrist, and co-medical
      stuff such as psychiatric social worker, physiotherapist, etc. is made up to
      discuss the curative course dependent on each psychosomatic problems of the
      patients with chronic low back pain in Liaison conference.

PMID- 15741687
TI  - [Rehabilitation for the patients with low-back pain].
AB  - The first choice for the treatment of low-back pain should be physical therapy,
      or rehabilitation. These are mainly divided into two modalities; passive and
      active modality. The former includes bed rest, hot pack, massage, and brace. The
      latter includes therapeutic exercise. The modality used should be dependent of
      the stages in each patient. Bed rest is indicated in the acute stage within a
      week after the occurrence low-back pain. The rest longer than a week is basically
      contraindicated, because of disuse syndrome such as muscle weakness,
      osteoporosis, and soft tissue contracture. Therapeutic exercise is the mainstay
      in the chronic stage. It includes trunk muscles strengthening exercise and
      stretching. Lumbar stabilization exercise has currently drawn attention for the
      treatment of low-back pain. Patient education such as back-school also plays an
      important role to manage low-back pain.

PMID- 15741688
TI  - [Drug management of low back pain].
AB  - NSAIDs and muscle relaxants effectively reduce acute nonspecific low back pain
      (LBP), different types of both drugs being equally effective. In general, there
      is no strong evidence for the effectiveness of medication for chronic nonspecific
      LBP. However, there is a possibility that administration of antidepressants is an
      intervention worthy of consideration in cases of LBP with no identifiable organic
      cause and resistant to other treatments.

PMID- 15741689
TI  - [Block treatment for low back pain--technical note].
AB  - Many types of block are used for treatment of low back pain. In the current
      paper, trigger-point block, facet block, ilio-sacral joint block, epidural block
      and nerve root infiltration (nerve root block), quite common procedures for
      treatment of low back pain, are introduced and technical notes are described.
      There are two important points for block treatment, one is the knowledge of
      anatomy and another is the knowledge of side effects. We must remember to prepare
      everything for side effects when block treatment is done.

PMID- 15741690
TI  - [Anterior lumbar interbody fusion for low back pain].
AB  - There are various causes of low back pain, but if the cause of low back pain was
      determined as a discogenic pain, anterior lumbar interbody fusion was indicated.
      The surgical treatment should be determined after MRI and other radiological
      imaging studies and pain response, and also it is important to examine the social
      factor and psychological status. Extra-peritoneal approach is selected for above
      L(4)-L(5) level, and trans-peritoneal approach is selected for L(5)-S(1). Recent
      endoscopic approaches to the anterior lumbar spine is also presented.

PMID- 15741691
TI  - [Indication and surgical methods of lumbosacral spinal fusion for lumbal
      degenerative diseases].
AB  - In degenerative lumbar spinal diseases with low back pain and leg pain, the
      indications for lumbar spinal fusion are not clear. It is unclear for the
      following reasons. The definition of instability is not clear. And it is also
      difficult to observe the exact source of the low back pain. In addition, there
      are limited numbers of randomized prospective study about the usefulness of spine
      fusion. Controversy still exists for when spinal instrumentation should be used.
      A spinal surgeon performs a posterolateral fusion or a posterior interbody fusion
      with or without instrumentation, mainly based on his experience and belief.

PMID- 15741692
TI  - [Practice of the low back pain treatment by acupuncture and moxibustion].
AB  - In oriental medicine, not only the local pathological state but also disharmony
      within the body and the stagnation of Ki are examined. For this purpose,
      diagnoses in modern western medicine are also used as references. The
      pathological condition is evaluated by the 4 diagnostic methods as original
      methods of oriental medicine, treatment points are decided, and acupuncture and
      moxibustion are performed. If meridians and reactive points that appear with Ki
      stagnation impairing natural healing ability can be determined, not only low back
      pain but also symptoms such as constipation disappear, resulting in harmony of
      the body and improvement in constitutional symptoms.

PMID- 15741693
TI  - [Physiological significance of calcitonin in fish].
AB  - The physiological role of calcitonin (CT) in fish has been partially elucidated.
      In teleosts, CT did not affect the calcium (Ca) and phosphate contents in bone
      and scales. In an experiment using Ca(45), CT did not show any change in the Ca
      flux of the scales. To examine the effect of CT on osteoclasts in teleosts,
      therefore, we developed a new culture system using goldfish scales. This system
      can detect osteoclastic and osteoblastic activities very sensitively using
      tartrate-resistant acid phosphatase and alkaline phosphatase as respective
      markers. We are the first to demonstrate that CT suppresses osteoclastic
      activities in teleosts as well as mammals. Using the sandwich type of an ELISA
      system with two polyclonal antibodies, we demonstrated that a considerable
      increase (more than twice) of plasma Ca triggered the secretion of CT from
      ultimobranchial glands in the feeding period but a slight increase of plasma Ca
      did not promote CT secretion. From the analyses of the plasma CT level and the
      expression of a CT receptor, we found that in teleosts, CT has the most important
      role in the reproductive period compared to other periods. In cartilaginous fish
      and cyclostomes as well as teleosts, CT has some roles in the reproductive
      period. These results suggest that CT in fish has a more important role in the
      reproductive physiology than in the Ca metabolism.

PMID- 15741694
TI  - [Effects of calcitonin on osteoclast].
AB  - Osteoclasts are the only cells that destroy and resorb bone. Calcitonin, a
      calcium regulatory hormone, strongly inhibits bone-resorbing activity of
      osteoclasts. The calcitonin-induced inhibition of osteoclast function is believed
      to be due to disruption of cytoskeletal organization (distraction of actin rings)
      and disappearance of the cellular polarity of osteoclasts. Calcitonin receptors
      are coupled to both cAMP-PKA- and Ca(2+)-PKC (protein kinase C)-mediated
      signaling pathways. Using mouse osteoclasts formed in vitro, it is shown that
      inhibitory effects of calcitonin on bone resorption is mainly mediated by the
      cAMP-PKA signal. This article describes the mechanism of calcitonin action in the
      suppression of osteoclast function.

PMID- 15741695
TI  - [Infection and plasma procalcitonin].
AB  - Procalcitonin, a propeptide of calcitonin, is normally produced in the C-cells of
      the thyroid gland, but it's plasma level markedly increases, mostly due to extra
      thyroidal production in cases of severe infections (bacterial, parasitic and
      fungal) with systemic manifestations, especially in the presence of septic shock.
      Since noninfectious inflammatory reaction, viral infection and localized
      bacterial infections manifest only small to modest increases of procalcitonin in
      plasma, procalcitonin levels may be useful in differentiating between these
      diseases and sepsis. In addition, it has been suggested that procalcitonin is an
      early and good marker of elevated cytokines in patients with sepsis, and that
      it's plasma level is correlated with Sepsis-related Organ Failure Assessment
      (SOFA) score. Since plasma procalcitonin is measured easily, quickly and
      accurately by immunoluminometric assay, it is useful for early diagnosis of
      sepsis in patients with severe systemic inflammatory response syndrome and as an
      indicator of severity of sepsis in such patients.

PMID- 15741696
TI  - [Calcitonin and renal mineral reabsorption].
AB  - Calcitonin and its receptor are well known for their ability to regulate
      osteoclast-mediated bone resorption. Calcitonin has been suggested to be a renal
      Ca(2+) and Mg(2+)-conserving hormone and may share similar signaling mechanisms
      with PTH. This review describes the characteristics of renal Ca(2+), Mg(2+) and
      Pi transport pathway and the physiological roles of calcitonin in renal mineral
      reabsorption.

PMID- 15741697
TI  - [Spinal anti-nociceptive effect of calcitonin in an osteoporotic model rat-
      functional recovery of descending serotonergic inhibition].
AB  - Although calcitonin is generally used to relieve chronic pain accompanying
      osteoporosis, little is known about what kind of noxious sensation is alleviated
      by calcitonin. We examined actions of calcitonin on nociceptive transmission in
      the spinal dorsal horn of ovariectomized (OVX) rats using in vivo patch-clamp
      technique. Inhibitory effect of serotonin on mechanical noxious inputs to dorsal
      horn neurons was reduced in OVX rats. This mechanical hyperalgesia observation in
      OVX rats was attenuated by calcitonin treatment.

PMID- 15741698
TI  - [Therapeutic effects of calcitonin on back pain in the patients with
      osteoporosis].
AB  - A prospective study was performed to clarify the therapeutic effect on calcitonin
      in the patients with osteoporosis using patient-based outcome measures. A total
      of 67 patients with primary osteoporosis who complained back pain were included
      in this study. All patients were administered calcitonin 20 Unit/week
      intramuscularly. The therapeutic effects were assessed using various patient
      based outcome measures before treatment, 2, 4 weeks and 3 months after treatment.
      We used Short form 12 for measuring general well-being, Roland Morris disability
      questionnaire for functional status associated with back pain, and visual
      analogue scale for pain intensity. Statistic analysis was performed using paired
      t test. Pain intensity and functional status were significantly recovered at 2
      weeks follow-up time and the effects were continued at 3 months follow-up time.
      Physical component summary (PCS) was recovered at 3 months follow-up tme, whereas
      mental component summary (MCS) was improved at 2 weeks follow-up time. These
      facts suggest that improvement of back pain using calcitonin correlates directly
      with recovery in functional status, indirectly with recovery in general well
      being.

PMID- 15741700
TI  - [Osteoporosis and the intake of meat and fish].
AB  - Usual intake of meat and fish may not be a risk factor or a protective factor for
      osteoporosis. When the large proportion of protein intake depends on the animal
      meat, it is possible to give adverse effects on bone metabolism. Fish is an
      important source of vitamins A and D. Although the adequate intake of these
      vitamins is indispensable for healthy bone, excessive intake of vitamin A would
      be harmful to the skeletal system.

PMID- 15741699
TI  - [Improvement of QOL in osteoporotic patients by calcitonin treatment].
AB  - Quality of life (QOL) is impaired in patients with osteoporosis, to which bodily
      pain greatly contributes. The presence of vertebral fractures detrimentally
      affects the patients' QOL in a dose-dependent manner. Calcitonin, with its potent
      analgesic action, markedly improves the various aspects of patients' QOL.
      Efficacy for the treatment of osteoporosis should be evaluated in terms of QOL
      also, in addition to the increase in bone mineral density and fracture
      prevention.

PMID- 15741701
TI  - [Jaws of fish 2].
AB  - Structure of Jaws in fish composed of mandibular and hyoid arches. Hyomandibular
      which is upper part of hyoid arch plays an important role of jaw suspension.
      Various jaw structures are developed in fish. One of the samples is protrusible
      upper jaw in cyprinid fish. Development of the protrusible jaw structure was
      related to degeneration of oral teeth and development of pharyngeal teeth in
      cyprinids.

PMID- 15741702
TI  - [Hypercalcemia complicated with status nervosus in an elderly patient on
      hemodialysis during parental nutrition].
AB  - An 89-year-old male patient on hemodialysis presented clouding of consciousness
      caused by hypoglycemia during taking an anti-diabetic agent. His somnolent state
      continued in spite of glucose dispensation, and parental nutrition was started by
      a nasogastric tube because he couldn't have peroral ingestion. Though his blood
      glucose level recovered normal, his consciousness disorder was suspended, and he
      showed remarkable hypercalcemia. He was dosed with elcatonin, and the parental
      nutrient was changed to the other one that contained less vitamin D and calcium,
      and so his serum calcium level diminished slowly but he showed drowsiness about a
      month long. After resumption of peroral ingestion, his consciousness restored to
      the former condition rapidly. This case suggests that careful observation is
      needed in less active dialysis patients with parental nutrition because nutrient
      contained vitamin D and calcium, which doesn't harm patients without renal
      insufficiency, may cause hypercalcemia.

PMID- 15741703
TI  - Nurse practitioners in community health settings today.

PMID- 15741704
TI  - Heroes in oral health and education.

PMID- 15741705
TI  - Affirmative action policy in medical school admissions.
AB  - Legal challenges to affirmative action are growing, a trend suggesting that a
      proactive stance is needed to maintain a policy that still has viability,
      legitimacy, and utility. Medical schools admissions offices in the United States
      emphasize the Medical College Admissions Test (MCAT), even though many studies
      have found that grade point averages are better single predictors of future
      academic achievement, regardless of the student's socioeconomic or racial
      category. The current essay suggests there is an overreliance on the MCAT in
      medical school admissions. Medical colleges should encourage the development of
      additional applicant selection criteria, while continuing to use affirmative
      action programs, in part to address the need for increased community-oriented
      health care.

PMID- 15741706
TI  - A socioeconomic profile of older adults with HIV.
AB  - The objective of this study was to assess the socioeconomic circumstances of
      older patients with HIV and acquired immunodeficiency syndrome (AIDS). The
      investigators compared subjects from a national probability sample of 2,864
      respondents from the HIV Cost and Services Utilization Study (HCSUS, 1996) with
      9,810 subjects from Wave 1 (1992) of the Health and Retirement Survey (HRS).
      Bivariate analyses compare demographic characteristics, financial resources, and
      health insurance status between older and younger adults and between older adults
      with HIV and the general population. It was found that nearly 10% of the HIV
      positive population is between the ages of 50 and 61 years. Older whites with HIV
      are mostly homosexual men who are more well educated, more often privately
      insured, and more financially stable than the HIV population as a whole. In
      contrast, older minorities with HIV possess few economic resources in either
      absolute or relative terms. The success of new drug therapies and the changing
      demographics of the HIV population necessitate innovative policies that promote
      labor force participation and continuous access to antiretroviral therapies.

PMID- 15741707
TI  - Sources and barriers to health care coverage for Haitian immigrants in Miami-Dade
      county, Florida.
AB  - Haitian immigrants represent one of the largest foreign-born groups in Florida.
      Limited information is available on the health care issues that they face. This
      study's objective was to identify and evaluate the sources of and barriers to
      health care coverage for the Haitian immigrant community of Miami-Dade County,
      Florida. Information was collected on demographic characteristic and health needs
      and access from a probability sample of county residents of Haitian origin. Chi
      square and logistic regression methods were used for data analysis. Only half of
      the participants had any type of health coverage, including 28% with private
      insurance and 15% with publicly financed coverage. Education, family income, U.S.
      citizenship status, length of U.S. residence, and English proficiency were
      associated with health coverage in bivariate analysis. Gender, citizenship,
      family income, and length of residence were also associated with coverage in
      adjusted analysis. These findings suggest that this community confronts serious
      access challenges that may negatively affect the health outcomes of Haitians in
      the U.S.

PMID- 15741708
TI  - Differential effects of messages for breast and cervical cancer screening.
AB  - The aim of this study was to compare responses to two interventions (personalized
      form [PF] letter messages versus personalized-tailored [PT] letter messages)
      using medical record data for promoting appointment scheduling and screening for
      breast and cervical cancer among urban low-income women from three ethnic groups:
      African-American, Mexican-American, and non-Hispanic white women. The 1,574 women
      participating in the randomized controlled trial were assigned to one of three
      groups: (1) PF letter, (2) PT letter, (3) control (no letter). Logistic
      regression analyses show that (1) personalized-tailored letters containing
      individualized references to recipients' cancer risk factors failed to increase
      rates of recommended cancer screening behaviors, especially among non-Hispanic
      white women; and that (2) in contrast, a personalized-form letter with general
      breast and cervical cancer screening messages increased cancer screening rates in
      this population, especially among non-Hispanic white and Mexican-American women.

PMID- 15741709
TI  - Racial distribution of dual-diagnosis clients in public sector mental health and
      drug treatment settings.
AB  - This study examined the racial distribution of dual-diagnosis clients in public
      sector residential mental health and drug treatment settings. In a sample of 179
      dual-diagnosis clients, there was a significantly larger proportion of blacks in
      the drug treatment cohort than the mental health cohort. There were black-white
      differences in the types of substance use disorders found, but not in the types
      of mental health disorders. Diagnostic and drug use pattern differences did not
      account for the differential racial distribution in the two settings. However,
      the racial distribution was explained by the recent history of service use in the
      two treatment sectors. In the 2 years after study entry, blacks were less likely
      than whites to receive mental health treatment and whites were less likely than
      blacks to receive drug treatment. The implications of these findings regarding
      the appropriate treatment for dual-diagnosis blacks and whites in the public
      sector are discussed.

PMID- 15741710
TI  - Inadequate access to care among children with asthma from Spanish-speaking
      families.
AB  - Despite substantial asthma prevalence and morbidity, children from Spanish
      speaking families are at high risk of inadequate maintenance therapy. The reasons
      for this remain unclear. The objective of this study was to compare patterns of
      asthma morbidity and access to care of children with asthma from Spanish-speaking
      and English-speaking families. Cross-sectional data from a nationally
      representative sample of children with asthma 2-17 years of age were analyzed
      from the 1999 National Health Interview Survey, conducted in both English and
      Spanish, with the preferred language identified at the time of the interview.
      Among the 1,228 children with asthma (physician-diagnosed asthma by parent
      report), 66 (3%) were from Spanish-speaking families and 1,162 (97%) were from
      English-speaking families. In a logistic regression model adjusting for gender,
      insurance, poverty (above or below the federal poverty level, based on reported
      family income and the U.S. Poverty Threshold produced annually by the Census
      Bureau), and race/ethnicity, children with asthma from Spanish-speaking families
      were one-third less likely to have a usual health care provider (odds ratio [OR]
      0.31, 95% confidence interval [CI] 0.1-0.8) than children with asthma from
      English-speaking families. Latino ethnicity was not independently associated with
      diminished continuity of care. These data indicate that children with asthma from
      Spanish-speaking families are less likely to experience continuity of health care
      than their counterparts from English-speaking families. Differences in continuity
      of care may contribute to inadequate asthma maintenance therapy among these
      children.

PMID- 15741711
TI  - Access for pregnant women on Medicaid: variation by race and ethnicity.
AB  - Disparities in early and adequate prenatal care and infant/maternal outcomes
      still exist between white and nonwhite populations. Although Medicaid expansions
      were intended to improve outcomes, eligible women often delay enrollment and
      access barriers remain. This study examines racial disparities among pregnant
      women in Florida, Georgia, New Jersey, and Texas. The disproportionate location
      of minorities enrolled in Medicaid in urban areas with greater physician supply
      was not found to increase office-based prenatal care among blacks. More local
      physicians, especially foreign medical graduates, sometimes increased access,
      largely for Hispanics. The presence and use of safety net providers did increase
      prenatal care use among minorities. This evidence lends support to policies to
      maintain safety net providers, which are perhaps better equipped than others to
      serve low-income populations. However, policies should encourage participation
      extending to all racial/ethnic groups by office-based physicians. The role of
      foreign medical graduates, who are more likely to participate in Medicaid, should
      be considered.

PMID- 15741712
TI  - The relationship between SCHIP enrollment and hospitalizations for ambulatory
      care sensitive conditions in California.
AB  - The State Children's Health Insurance Program (SCHIP) was implemented in 1998,
      providing new funds for states to cover uninsured children. This study examines
      the relationship between SCHIP implementation in California and hospitalizations
      for ambulatory care sensitive conditions (ACSCs), an indicator of primary care
      access and quality. We use administrative SCHIP enrollment records for urban
      California counties, linked with corresponding rates of hospitalization for seven
      ACSCs among children ages 1-18 for 1996-2000. Results from multivariate
      regression models indicate that increases of 1 percentage point in SCHIP
      enrollment are associated with reductions of 0.42 ACSC admissions per 100,000
      children age 1-18 (p = 0.009). Models that use lagged effects of SCHIP enrollment
      indicate an even stronger relationship. These are population-level relationships,
      and translate to much larger effects on the specific population subset that
      enrolled in SCHIP. These results suggest a strong beneficial effect of SCHIP on
      primary care among the children covered.

PMID- 15741713
TI  - Recommendations for nutrition interventions with overweight African-American
      adolescents and young adults at the Atlanta Job Corps Center.
AB  - Focus groups were used to gain insight into the nutrition-related attitudes and
      motivations of overweight African-American adolescents and young adults enrolled
      in the Atlanta Job Corps Center in preparation for designing an effective and
      culturally appropriate nutrition intervention for this population. Eighteen
      students and 18 staff members participated in six different focus groups. Focus
      group themes suggest that an intervention with this target group should address
      overeating, proper diet composition, emotional eating, long-term consequences of
      a poor diet, group work, and incentives. Limiting food portions, offering
      healthy, appealing food choices, and displaying nutritional content of foods in
      the cafeteria were also suggested. It was also suggested that the intervention
      should be ongoing and led by someone who is patient, supportive, and has overcome
      an overweight problem. An intervention based on these recommendations can be
      specifically tailored to this target group and, potentially, be effective in
      changing dietary behaviors and lifestyle.

PMID- 15741714
TI  - An evaluation of a medical outreach program targeting unstably housed HIV
      infected individuals.
AB  - The objective of this study was to evaluate a medical outreach program that
      targets unstably housed human immunodeficiency virus (HIV)-infected individuals.
      One hundred sixty-one cross-sectional interviews were conducted prior to and
      after establishing a medical outreach program in single room occupancy hotels.
      Participants' mean age was 42 years; 58% were men, 95% minority, and 59% active
      substance users. The postintervention group was more likely to have a regular
      health care provider (p = 0.02), and take Pneumocystis carinii pneumonia
      prophylaxis (p = 0.03) and antiretroviral medication (p = 0.02) than the pre
      intervention group. Quality of care was more positively perceived in the
      postintervention group (p = 0.001). On multivariate analysis the postintervention
      group remained more likely to have a regular provider (OR = 5.3, p = 0.02), take
      antiretroviral medication (OR = 5.7, p = 0.02), and have a better perception of
      quality of care (OR = 4.9, p = 0.003). A medical outreach program targeting
      unstably housed HIV-infected individuals was associated with increased use of
      regular medical care and improved perceived quality of care.

PMID- 15741715
TI  - Do managed care plans reduce racial disparities in preventive care?
AB  - This study was designed to determine whether managed care plans reduce racial
      disparities in use of influenza vaccination, mammography, and prostate-specific
      antigen screening. The study analyzed the use of three types of preventive care
      in a population-based sample of adults who were 65 years or older and were
      enrolled in a Medicare managed care (MMC) or fee-for-service (FFS) plan in
      Allegheny County, Pennsylvania. The study sample included 463 African Americans
      and 592 whites. Fewer African Americans than whites reported having had an
      influenza vaccination (64.4% versus 76.5%; p < 0.01) or a prostate-specific
      antigen test (64% versus 71.2%; p = 0.09) during the previous year. Slightly more
      African Americans than white women reported having had a mammogram (66.1% versus
      63.8%). Logistic regression showed that, regardless of health plan type, African
      Americans were significantly less likely than whites to have an influenza
      vaccination (p < 0.05). A MMC plan did not narrow racial differences in
      preventive care. Reducing disparities may require interventions developed for
      specific racial/ethnic groups.

PMID- 15741716
TI  - Literacy and knowledge, attitudes and behavior about mammography in Latinas.
AB  - This cross-sectional study explored the association between functional health
      literacy and the knowledge, beliefs, attitudes, and behavior about mammography
      and self-breast examination in a sample of Latinas attending community health
      clinics in Philadelphia. The results show that 70% of Latinas had inadequate or
      marginal functional health literacy. In Latinas, functional health literacy is
      only weakly associated with knowledge and not associated with beliefs and
      attitudes about screening mammography, but is significantly associated with
      having ever had a mammogram. After adjusting for demographic characteristics,
      functional health literacy was significantly associated with having ever had a
      mammogram (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02-1.27). These
      findings suggest that Latinas with poor functional health literacy are less
      likely to undergo mammography. Future research should target increasing the
      knowledge about and rates of screening mammography in patients with low
      functional health literacy.

PMID- 15741718
TI  - The diffusion-weighted lesion in acute stroke: heterogeneous patterns of
      flow/metabolism uncoupling as assessed by quantitative positron emission
      tomography.
AB  - BACKGROUND: To investigate what the hyperintense lesion in diffusion-weighted
      imaging (DWI) of acute ischaemic stroke represents metabolically, we
      prospectively imaged acute carotid-territory stroke patients with DWI along with
      fully quantitative positron emission tomography (PET), which gives physiological
      maps of cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2)
      and the oxygen extraction fraction (OEF). METHOD: Of 10 patients who consented, 5
      (3 males, 2 females, 53-84 years, NIHSS 6-16) completed the imaging protocol of
      back-to-back DWI and PET within 21 (mean 15.7, range 7-21) h of stroke onset. All
      images were co-registered with the DWI lesion forming a region of interest (ROI)
      that was transferred to the PET parametric maps (OEF, CBF, CMRO2). Patterns of
      blood flow and metabolism were assessed within the DWI ROI. RESULTS: Within the
      DWI lesions, the following patterns were observed: very low CBF and
      CMRO2/variable OEF; low CBF/high OEF, and high CBF/low OEF. There was a
      heterogeneity of patterns between and within DWI lesions. In addition, areas of
      hyperperfusion (with low OEF) and areas of hypoperfusion (with high OEF) were
      seen outside the DWI lesions. CONCLUSION: The DWI lesion does not have a single
      flow/metabolism counterpart, suggesting that it reflects various stages of the
      ischaemic process.

PMID- 15741720
TI  - Detection of approximal caries in 5-year-old Swedish children.
AB  - The aim was to assess how accurately some commonly used risk factors/risk markers
      (predictors) for caries development could identify children with and without
      approximal caries as judged from bitewing radiography. Two hundred and sixty
      seven consecutive 5-year-old children from two Swedish cities participated. Three
      experienced dentists examined the children. The predictors were the overall dmfs
      (decayed, missing and filled surfaces) value (canines and molars), the number of
      occlusal dmfs, the frequency of intake of between-meal sugary products, visible
      plaque on free smooth surfaces of second primary molars, toothbrushing habits and
      (before bitewing examination) an overall judgement by the examining dentist. The
      mean dmfs value without bitewing examination was 0.40 (SD = 1.22). Twelve percent
      of the children had at least one dentin lesion and 33% at least one enamel lesion
      that were detected from bitewing examination only. The gain from adding bitewing
      examination to clinical examination amounted to a mean of 1.2 approximal enamel
      and/or dentin lesions. The ability to correctly identify children with approximal
      caries from the predictors was limited; sensitivity ranged from 0.27 to 0.75 and
      specificity ranged from 0.41 to 0.93. The single best predictor was the dentist's
      overall judgement with an average precision of 73%; average sensitivity for the
      presence of enamel and dentin lesions was 0.48 and for the presence of dentin
      lesions 0.66. The rest of the predictors added little to the predictive power. It
      is concluded that 33% of the 5-year-olds, representing a low caries prevalence
      population, benefited from bitewing examination. The ability to identify these
      children from the predictors was, however, limited.

PMID- 15741719
TI  - Behavioural and demographic factors during early childhood and poor dental health
      at 10 years of age.
AB  - The aim was to elucidate whether variables recorded in early childhood would have
      a long-lasting predictive value of poor dental health at the age of 10 years in a
      prospectively followed Finnish population-based cohort setting. The second aim
      was to find new tools for preventive work in order to improve dental health among
      children. Poor dental health (dmft + DMFT >or= 5) at 10 years of age was
      associated with child's nocturnal juice drinking at 18 months. It was associated
      with the following factors at age 3 years: frequent consumption of sweets;
      infrequent tooth brushing; plaque and caries on teeth. Of family factors, the
      following were significant: father's young age at birth of the child; mother's
      basic 9-year education; mother's caries (i.e. several carious teeth per year),
      and father's infrequent tooth brushing. Early childhood risk factors of poor
      dental health seem to be stable even after 10 years of life and the changing of
      teeth from primary to permanent ones. In preventive work, dental health care
      staff could offer support to those parents with risk factors in their child
      rearing tasks.

PMID- 15741721
TI  - Plaque fluoride concentrations in a community without water fluoridation: effects
      of calcium and use of a fluoride or placebo dentifrice.
AB  - The results of a recent study by Whitford et al. [Caries Res 2002;36:256-265]
      with subjects whose drinking water was fluoridated led to two major conclusions:
      (1) Compared to the use of a placebo dentifrice, plaque fluoride concentrations
      ([F]) throughout much of the day are not significantly increased by the use of an
      F dentifrice but (2) they are positively related to plaque [Ca] (p = 0.0001). The
      present double-blind, double-crossover study with 16 subjects used the same
      protocol and was done to: (1) determine the effects of the use of an F dentifrice
      on salivary and plaque [F] in a community without water fluoridation and (2)
      further examine the relationship between plaque [Ca] and [F]. Following the use
      of an F dentifrice or placebo for one week, whole saliva and plaque were
      collected 1.0 and 12 h after the last use of the products. The study was repeated
      to include rinsing with a 20 mmol/l CaCl(2) solution immediately before the use
      of the dentifrices. The CaCl(2) rinse had only minor effects on salivary [Ca] and
      [F] and none on the plaque concentrations. Unlike the results found in the
      fluoridated community, all salivary and plaque [F] associated with the use of the
      F dentifrice were significantly higher than those associated with the use of the
      placebo. The results suggest that the cariostatic effectiveness of an F
      dentifrice should be greater in areas without water fluoridation. As noted
      previously, plaque [F] were positively related to plaque [Ca] (p = 0.0001).

PMID- 15741722
TI  - The effects of a supervised toothbrushing programme on the caries increment of
      primary school children, initially aged 5-6 years.
AB  - Children in the London Boroughs of Kensington, Chelsea and Westminster have one
      of the highest levels of caries in England and Wales. In 1997/98, the mean dmft
      for 5-year-old children was 2.83 with only 45.9% of the children being caries
      free. The aim of this study was to determine whether teacher-supervised
      toothbrushing, once a day, at school, during term time, with commercial
      toothpaste containing 1,450 ppm fluoride, could reduce dental caries in primary
      school children when compared with children from the same community who did not
      receive this intervention. A total of 517 children (mean age 5.63 years) were
      recruited for the study. Class teachers were trained individually by the same
      dental hygienist in an appropriate toothbrushing technique for young children.
      Children in the intervention group brushed once a day at school. All examinations
      were by visual assessment only. All teeth present were assessed using the BASCD
      criteria. For children in the intervention group, the overall caries increment
      (2.60) was significantly less (10.9%; p < 0.001) than for children in the non
      intervention group (2.92). Among different tooth surfaces, the difference in
      caries increment between the intervention group (0.78) and the non-intervention
      group (1.03) was greatest for the proximal surfaces (21.4%; p < 0.01). In
      conclusion, this study suggests that a programme of daily teacher-supervised
      toothbrushing with fluoride toothpaste can be effectively targeted into socially
      deprived communities and a significant reduction in dental caries can thereby be
      achieved especially among caries-susceptible children.

PMID- 15741723
TI  - Efficacy of fluoride toothpaste in preventing demineralization of smooth dentin
      surfaces and narrow grooves in situ under frequent exposures to sucrose or
      bananas.
AB  - The use of models simulating fissures allows studying demineralization at sites
      that are most prone to caries in vivo. In practice, most in situ models use flat
      surfaces. Our objectives were: (1) to compare the demineralizing potential of
      sucrose solution with that of bananas and (2) to study the effect of fluoride
      toothpaste on demineralization in situ in an easily accessible site and a plaque
      stagnation site. Four volunteers wore bovine dentin specimens with narrow grooves
      and a smooth surface for two 1-week in situ periods, with eight 1-min sugar
      exposures daily: either by a rinse with 10% sucrose, or by consumption of a piece
      of banana. Twice daily, the appliance was dipped in toothpaste slurry of a
      control (fluoride-free) toothpaste at one side and a fluoride toothpaste at the
      contralateral side. Demineralization was assessed by transversal
      microradiography. We found no difference in dentin demineralization after
      frequent exposure to either sucrose solution or bananas. Fluoride toothpaste
      effectively protected dentin only at the smooth surface. In the grooves, fluoride
      affected the demineralization pattern; it drove lesions towards the bottom of the
      groove. We conclude that assessing only smooth surfaces in intraoral tests might
      lead to underestimated food cariogenicity and to overestimated efficacy of
      fluoride-containing toothpaste.

PMID- 15741724
TI  - Effect of sucrose containing iron (II) on dental biofilm and enamel
      demineralization in situ.
AB  - Since the effect of iron (Fe) on the cariogenicity of sucrose in humans is
      unexplored, this study assessed in situ the effect of Fe co-crystallized with
      sucrose (Fe-sucrose) topically applied in vitro on the acidogenicity, biochemical
      and microbiological composition of the dental biofilm formed in vivo and on the
      demineralization of the enamel. During two phases of 14 days each, 16 volunteers
      wore palatal appliances containing blocks of human enamel, which were submitted
      to four groups of separate treatments: (1) water; (2) 20% sucrose; (3) 20% (w/v)
      sucrose plus 18 microg Fe/ml, and (4) 20% (w/v) sucrose plus 70 microg Fe/ml. The
      solutions were dripped onto the blocks 8 times per day. The biofilms formed on
      the blocks were analyzed with respect to acidogenicity, biochemical and
      microbiological composition. Mineral loss was determined on enamel by surface and
      cross-sectional microhardness. Lower demineralization was found in the blocks
      subjected to Fe-sucrose (70 microg Fe/ml) than in those treated with sucrose (p <
      0.05). This concentration of Fe also reduced significantly the populations of
      mutans streptococci in the biofilm formed on the blocks. In conclusion, our data
      suggest that Fe may reduce in situ the cariogenic potential of sucrose and the
      effect seems to be related to the reduction in the populations of mutans
      streptococci in the dental biofilm formed.

PMID- 15741725
TI  - Nitric oxide concentrations in saliva and dental plaque in relation to caries
      experience and oral hygiene.
AB  - The aim of the study was to determine the correlation of the antibacterial
      substance nitric oxide (NO) with dental caries in vivo. Salivary and dental
      plaque NO concentrations were analyzed by the Griess method in 11 subjects with
      high DMFT index and simplified oral hygiene index (OHI-S), 11 with low DMFT and
      OHI-S. Subjects with high DMFT and OHI-S had significantly higher NO
      concentrations in saliva (71.5 microM) and plaque (83.5 microM) than those with
      low DMFT and OHI-S (33.2 and 61.1 microM in saliva and plaque, respectively).
      Plaque NO concentrations were significantly higher than in saliva in both groups.
      NO production might be a host defense mechanism when dental caries increases or
      oral hygiene deteriorates.

PMID- 15741726
TI  - Influence of the organic matrix on root dentine erosion by citric acid.
AB  - This investigation was conducted in an attempt to clarify the role of the organic
      matrix in bovine dentine demineralisation by 1% citric acid. Dentine slabs (n =
      15) were treated for 2 min with 10% sodium hypochlorite (NaOCl, a strong protein
      solvent), 2% glutaraldehyde (GDA, a protein fixative) or deionised water (DIW, as
      negative control) prior to each of 5 demineralisation periods of 30 min. The
      mineral loss (DeltaZ), lesion depth (LD) and surface loss (SL) were determined
      after each period of demineralisation, by transverse microradiography. The NaOCl
      treated group showed higher DeltaZ and LD than the GDA- and DIW-treated groups.
      No differences between GDA and DIW groups were found. The DeltaZ and LD profiles
      were explained by quadratic fits (r(2) >0.80; p = 0.001) in all groups. SL was
      detected only in the NaOCl-treated group. The data suggested that the maintenance
      of the organic matrix in the lesion might be important to reduce the erosion
      progression rate.

PMID- 15741727
TI  - Thickness measurement of worn molar cusps by ultrasound.
AB  - This study aimed to evaluate the effectiveness of an ultrasonic system for in
      vitro measurement of cusp tips of human teeth. Each worn cusp of 12 molar teeth
      was measured with an industrial ultrasonic system. The teeth were sectioned and
      measured by polarized light microscopy. The ultrasonic measurements and
      histological readings were moderately correlated (r = 0.601, p < 0.01). The
      ultrasonic system used in this study seemed a promising method for measuring
      thickness of worn cusp tips of extracted human molar teeth.

PMID- 15741728
TI  - The influence of the calibration mode of a laser fluorescence device on caries
      detection.
AB  - The aim of the present study was to assess the influence of the calibration mode
      of a laser fluorescence measurement device on caries detection. While positioning
      the probe on an occlusal carious lesion or stained fissure using a clamp, the
      occlusal surface of each of 62 teeth was covered with a light-body silicone
      impression material to facilitate a reproducible probe position. Then,
      measurements of the occlusal lesions were performed after standard and individual
      calibration at four non-carious areas on the buccal surface of each tooth. Mean
      laser fluorescence values of the occlusal reading point following standard
      calibration were about 4-5 units higher compared to values measured after
      individual calibration. After 1 week, readings after both standard and individual
      calibration were not different from baseline values (p > 0.05). During individual
      calibration, a mean range of about 2 units could be observed when comparing the
      readings of the occlusal reading point with respect to the four different areas
      of each buccal surface. The present study indicates that laser fluorescence
      readings are dependent on the mode of calibration. Moreover, for individual
      calibration, the probe position has to be recorded carefully. It is suggested
      that the same mode of calibration should always be used, when employing laser
      fluorescence measurements for longitudinal caries monitoring.

PMID- 15741729
TI  - Comparative fluorescence spectroscopy shows differences in noncavitated enamel
      lesions.
AB  - The aim of this study was to compare emission spectra from noncavitated enamel
      caries with different degrees of discoloration under a wide range of excitation
      wavelengths. Freshly extracted human molars with white spot, light discolored and
      dark discolored brown spot enamel caries were selected (n = 4 each). Rectangular
      blocks (3.5 x 3.5 mm) were cut from the carious area and a corresponding sound
      area of the same tooth. Emission spectra were recorded from carious and the
      corresponding sound areas using a fluorescence spectrophotometer at excitation
      wavelengths from 360 nm up to 580 nm in steps of 20 nm. The specimens were
      submerged in water during measurement. The spectra were corrected and normalized
      to peak intensity for comparisons between spectra from sound and carious areas of
      each tooth. Excitation spectra were recorded for selected emission wavelengths
      that showed maximum intensity. Emission spectra of all types of carious lesions
      were shifted towards longer wavelengths (red shift) when compared to the spectra
      of the corresponding sound enamel. The red shift was highest for dark brown spot
      lesions and lowest for white spot lesions (p <or= 0.001). Distinct fluorescence
      bands within 600-700 nm typical for porphyrin compounds were strongest for
      excitation wavelengths from 400 to 420 nm and present in most of the lesions
      investigated.

PMID- 15741730
TI  - Effect of plaque fluoride released from a glass-ionomer cement on enamel
      remineralization in situ.

PMID- 15741731
TI  - Differential role for mitogen-activated protein kinases in IgE-dependent
      signaling in human peripheral blood basophils: in contrast to p38 MAPK, c-Jun N
      terminal kinase is poorly expressed and does not appear to control mediator
      release.
AB  - BACKGROUND: Exposure of human basophils to allergens results in a rapid secretion
      of histamine, LTC(4), IL-4 and IL-13, which dominate both the symptomology of
      allergic diseases and support the underlying Th2/IgE predominance associated with
      these reactions. The IgE-dependent release of these mediators in basophils
      crucially involves PI 3-kinase and the subsequent activation of p38 MAPK and
      ERK1&2. Here, we investigated the role of the third major member of the mitogen
      activated kinase family, namely the c-Jun amino terminal kinase (JNK), which is
      rapidly activated following IgE receptor cross-linking in murine mast cells.
      METHODS: Human basophils were highly purified by magnetic cell sorting. The
      activities of various intracellular signaling components, in basophils that had
      been stimulated under various conditions, were assessed by Western blotting.
      Mediator secretions were also determined using either spectrofluorometric
      analysis (histamine) or ELISA (LTC(4), IL-4 and IL-13). RESULTS: Our results show
      that while JNK is moderately expressed in human basophils, it is not consistently
      phosphorylated upon anti-IgE stimulation. Phosphorylation of the transcription
      factor c-Jun, a downstream target of JNK, was also undetected in contrast to p38
      MAPK and ERK1&2, which were clearly activated following anti-IgE stimulation of
      the cells. Additionally, inhibitors of the JNK pathway failed to prevent basophil
      mediator release and had no effect on the phosphorylation of p38 MAPK or ERK1&2
      at concentrations which were specific for JNK blockade. CONCLUSIONS: These data
      suggest major differences in utilizing various members of the mitogen-activated
      kinase family in the signal transduction cascade of IgE-receptor-bearing cells.

PMID- 15741732
TI  - Is immunotherapy-induced birch-pollen-specific IgG4 a marker for decreased
      allergen-specific sensitivity?
AB  - BACKGROUND: The role of IgG4 during allergen-specific immunotherapy (SIT) is
      still controversial. The available studies present paramount differences in in
      vitro techniques, allergens, and clinical outcome parameters. By implementing a
      sensitive method, and pivotal clinical outcome parameters, we wanted to ascertain
      the utility of IgG4 as a clinical marker of decreased allergen-specific
      sensitivity to a common aeroallergen. METHODS: Sera were drawn from 23 birch
      pollen-allergic patients during a placebo-controlled clinical trial on birch
      pollen SIT. Seventeen patients received active treatment. Blood samples were
      drawn at 0, 2, 4, 7, and 30 treatment weeks, and 36 months. The binding activity
      of autologous IgG, IgG4, IgE, and IgE- and/or IgG-depleted serum to (125)I
      labelled recombinant Bet v 1 was assessed in a fluid-phase radioimmunoassay.
      Disease severity was assessed subjectively on a visual analogue scale (VAS), and
      objectively by intradermal late-phase reaction diameters. RESULTS: Before SIT
      IgG4 fraction of IgG-allergen binding varied from 4 to 74%, with a median of 36%,
      increasing to 71% after 36 months. Changes in IgG4 or IgG4/IgG fraction were not
      correlated to clinical outcome parameters. Changes in IgG allergen binding and
      VAS were significantly correlated (sigma = 0.72; p < 0.05). SIT increased the
      serum-blocking activity of IgE allergen binding from 25% before SIT to 80% after
      SIT. No changes were observed in the placebo group. CONCLUSION: The data suggest
      that IgG4 per se is a poor marker of decreased allergen-specific sensitivity to
      birch pollen, both as a single measurement and as delta values.

PMID- 15741733
TI  - Mouse strain specificity of the IgE response to the major allergens of Phleum
      pratense.
AB  - BACKGROUND: IgE immune responses against major allergens from Phleum pratense in
      low- and high-responder mouse strains were compared and the influence of alum was
      assessed, in order to evaluate the effect of the genetic background and adjuvants
      on IgE reactivity in a mouse model for P. pratense allergy. METHODS: Different
      mouse strains and F1 offspring were sensitized with P. pratense pollen extract.
      Serum IgE levels, the induction of specific IgE antibodies and immediate
      cutaneous hypersensitivity reactions were monitored by ELISA, Western blot and a
      skin test, respectively. RESULTS: All mouse strains investigated mounted an IgE
      response and exhibited a positive skin test to pollen extract. Differences were
      seen in the level of total serum IgE and in specific IgE reactivity to different
      major allergens of P. pratense. Notable differences were seen in IgE reactivity
      and immediate hypersensitivity against Phl p 1, which were only observed in SJL/j
      mice. The foremost influence of alum was on total IgE production levels.
      CONCLUSIONS: Alum is not necessary as an adjuvant to elicit IgE reactivity
      against the clinically relevant allergens of P. pratense, since even low
      responder mouse strains mounted a hypersensitivity reaction after sensitization
      without the adjuvant using otherwise identical sensitization strategies.
      Moreover, when analyzing the allergenicity of a compound, the hypersensitivity
      response of different mouse strains should be considered, as implicated by the
      differential results obtained for IgE reactivity against Phl p 1. Lastly, a
      genetic component may be involved in IgE reactivity to Phl p 1.

PMID- 15741734
TI  - Comparison of the effects of quinapril and losartan on carotid artery intima
      media thickness in patients with mild-to-moderate arterial hypertension.
AB  - BACKGROUND: Ultrasonographic evidence of increased carotid intima-media thickness
      (IMT) is known to be associated with generalized atherosclerosis. Therapeutic
      blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme
      (ACE) inhibitors reportedly reduces carotid IMT in humans. However, there has
      been no head-to-head comparison of the effects of ACE inhibitor and angiotensin
      receptor blocker (ARB), a newer type of RAS inhibitor, on carotid IMT. METHODS:
      57 hypertensive patients were randomly assigned to treatment with one of two
      antihypertensive drugs: ACE inhibitor (quinapril; n = 25, group Q) or ARB
      (losartan; n = 18, group L). RESULTS: After 1 year of treatment, a similar
      decrease in mean blood pressure was observed in all groups. Carotid IMT was
      decreased significantly in group Q (10% decrease, p < 0.05) but did not change in
      group L. There were no significant changes in other atherosclerotic factors
      between these two groups. CONCLUSION: Our findings suggest that the
      antiatherosclerotic effect of quinapril is more potent than that of losartan in
      hypertensive patients. This effect appears unrelated to the drug's
      antihypertensive action or to traditional atherosclerotic factors.

PMID- 15741735
TI  - Salt in the wound: a possible role of Na+ gradient in chlamydial infection.
AB  - Genome analysis has revealed the presence of key components of the Na(+)
      chemiosmotic cycle, including the primary Na(+) pump (Na(+)-translocating
      NADH:ubiquinone oxidoreductase), in the cytoplasmic membrane of two ubiquitous
      human pathogens, Chlamydia trachomatis and Chlamydiophyla pneumoniae. This
      observation seemed paradoxical in the case of obligatory intracellular parasites
      because the Na(+) cycle is thought to be primarily a mechanism that enhances the
      adaptive potential in free-living bacteria that are often facing drastic changes
      in the salinity and pH of the environment. We present a model suggesting that
      operation of the Na(+) cycle may play an important role in the course of
      chlamydial infection, when the Na(+) and H(+) homeostasis of the host cell become
      severely impaired. This introduces the intriguing possibility of the application
      of drugs targeting Na(+)-transporting enzymes to chlamydial infections, which are
      notoriously difficult to treat.

PMID- 15741736
TI  - Membrane targeting of a bacterial virulence factor harbouring an extended signal
      peptide.
AB  - Filamentous haemagglutinin (FHA) is the major adhesin of Bordetella pertussis,
      the whooping cough agent. FHA is synthesized as a 367-kDa precursor harbouring a
      remarkably long signal peptide with an N-terminal extension that is conserved
      among related virulence proteins. FHA is secreted via the two-partner secretion
      pathway that involves transport across the outer membrane by a cognate
      transporter protein. Here we have analyzed the mechanism by which FHA is targeted
      to, and translocated across, the inner membrane. Studies were performed both in
      vitro using Escherichia coli inside-out inner membrane vesicles and in vivo by
      pulse-chase labelling of Bordetella pertussis cells. The data collectively
      indicate that like classical periplasmic and outer membrane proteins, FHA
      requires SecA and SecB for its export through the SecYEG translocon in the inner
      membrane. Although short nascent chains of FHA were found to cross-link to signal
      recognition particle (SRP), we did not obtain indication for an SRP-dependent, co
      translational membrane targeting provoked by the FHA signal sequence. Our results
      rule out that the extended signal peptide of FHA determines a specific mode of
      membrane targeting but rather suggest that it might influence the export rate at
      the inner membrane.

PMID- 15741737
TI  - How tyrosine phosphorylation affects the UDP-glucose dehydrogenase activity of
      Bacillus subtilis YwqF.
AB  - The UDP-glucose dehydrogenase activity of Bacillus subtilis YwqF is regulated by
      reversible phosphorylation on a tyrosine residue. This reaction, which is
      catalyzed by the protein-tyrosine kinase YwqD, activates the enzyme, while
      dephosphorylation of phosphotyrosine-YwqF by the phosphotyrosine-protein
      phosphatase YwqE reduces its enzyme activity. Our kinetic data indicate that the
      phosphorylated and unphosphorylated forms of YwqF differ in binding the
      substrates. The UDP-glucose dehydrogenase reaction catalyzed by YwqF is inhibited
      by one of its substrates, UDP-glucose, and the extent of this inhibition seems to
      be reduced upon YwqF phosphorylation. We propose that this effect could at least
      partly account for the observed activation of YwqF induced by tyrosine
      phosphorylation. Potential physiological implications of this finding are
      discussed.

PMID- 15741738
TI  - Sucrose fermentation by Saccharomyces cerevisiae lacking hexose transport.
AB  - Sucrose is the major carbon source used by Saccharomyces cerevisiae during
      production of baker's yeast, fuel ethanol and several distilled beverages. It is
      generally accepted that sucrose fermentation proceeds through extracellular
      hydrolysis of the sugar, mediated by the periplasmic invertase, producing glucose
      and fructose that are transported into the cells and metabolized. In the present
      work we analyzed the contribution to sucrose fermentation of a poorly
      characterized pathway of sucrose utilization by S. cerevisiae cells, the active
      transport of the sugar through the plasma membrane and its intracellular
      hydrolysis. A yeast strain that lacks the major hexose transporters (hxt1-hxt7
      and gal2) is incapable of growing on or fermenting glucose or fructose. Our
      results show that this hxt-null strain is still able to ferment sucrose due to
      direct uptake of the sugar into the cells. Deletion of the AGT1 gene, which
      encodes a high-affinity sucrose-H(+) symporter, rendered cells incapable of
      sucrose fermentation. Since sucrose is not an inducer of the permease, expression
      of the AGT1 must be constitutive in order to allow growth of the hxt-null strain
      on sucrose. The molecular characterization of active sucrose transport and
      fermentation by S. cerevisiae cells opens new opportunities to optimize yeasts
      for sugarcane-based industrial processes.

PMID- 15741739
TI  - Identification of mimotopes of the Japanese encephalitis virus envelope protein
      using phage-displayed combinatorial peptide library.
AB  - The phage-displayed combinatorial peptide library is a revolutionary method for
      discovering epitopes, in particular conformational epitopes. In this study, we
      characterized a Japanese encephalitis virus (JEV) conformational epitope by
      biopanning of phage-displayed random peptide libraries with a JEV envelope (E)
      protein-specific monoclonal antibody (mAb) 2H2. Eleven identified phage clones
      with high affinity to mAb 2H2 were identified using direct and inhibitory binding
      ELISA. Sequence alignment, structure modeling and mutational analysis revealed
      that the identified mimotopes for mAb 2H2 possess a conserved motif
      X(1)(D/E)(Y/T/S)X(2), fitting into a region at the domain III lateral surface of
      the E protein. The results of our study could provide useful information on the
      development of effective mimotope-based vaccines and diagnostic kits for the JEV
      infection.

PMID- 15741740
TI  - The gellan gum biosynthetic genes gelC and gelE encode two separate polypeptides
      homologous to the activator and the kinase domains of tyrosine autokinases.
AB  - The high-molecular-weight exopolysaccharide gellan is an important commercial
      gelling agent produced in high yield by the Gram-negative bacterium Sphingomonas
      elodea ATCC 31461. The cluster of genes required for gellan biosynthesis contains
      the genes gelC and gelE. These encode for two polypeptides homologous to the
      activator domain and the kinase domain, respectively, of bacterial
      autophosphorylating tyrosine kinases involved in polysaccharide chain length
      determination. The GelC/GelE pair is an exception to the biochemically
      characterized Gram-negative tyrosine autokinases since it consists of two
      polypeptides instead of a single one. The deletion of gelC or gelE resulted in
      the abolishment of gellan in the culture medium confirming their role in gellan
      biosynthesis. In addition, ATP-binding assays confirmed the predicted ATP-binding
      ability of GelE. Interestingly, GelE contains an unusual Walker A sequence
      (ASTGVGCS), where the invariant lysine is replaced by a cysteine. This residue
      was replaced by alanine or lysine and although both mutant proteins were able to
      restore gellan production by complementation of the gelE deletion mutant to the
      production level observed with native GelE, only the mutated GelE where the
      cysteine was replaced by alanine was demonstrated to bind ATP in vitro. The
      importance of specific tyrosine residues present in the C-terminal domain of GelE
      in gellan assembly was also determined. The tyrosine residue at position 198
      appears to be essential for the synthesis of high-molecular-weight gellan,
      although other tyrosine residues may additionally contribute to GelE biological
      function.

PMID- 15741741
TI  - Biological implications of Mycobacterium leprae gene expression during infection.
AB  - The genome of Mycobacterium leprae, the etiologic agent of leprosy, has been
      sequenced and annotated revealing a genome in apparent disarray and in stark
      contrast to the genome of the related human pathogen, M. tuberculosis. With less
      than 50% coding capacity of a 3.3-Mb genome and 1,116 pseudogenes, the remaining
      genes help define the minimal gene set necessary for in vivo survival of this
      mycobacterial pathogen as well as genes potentially required for infection and
      pathogenesis seen in leprosy. To identify genes transcribed during infection, we
      surveyed gene transcripts from M. leprae growing in athymic nude mice using
      reverse transcriptase-polymerase chain reaction (RT-PCR) and cross-species DNA
      microarray technologies. Transcripts were detected for 221 open reading frames,
      which included genes involved in DNA replication, cell division, SecA-dependent
      protein secretion, energy production, intermediary metabolism, iron transport and
      storage and genes associated with virulence. These results suggest that M. leprae
      actively catabolizes fatty acids for energy, produces a large number of secretory
      proteins, utilizes the full array of sigma factors available, produces several
      proteins involved in iron transport, storage and regulation in the absence of
      recognizable genes encoding iron scavengers and transcribes several genes
      associated with virulence in M. tuberculosis. When transcript levels of 9 of
      these genes were compared from M. leprae derived from lesions of multibacillary
      leprosy patients and infected nude mouse foot pad tissue using quantitative real
      time RT-PCR, gene transcript levels were comparable for all but one of these
      genes, supporting the continued use of the foot pad infection model for M. leprae
      gene expression profiling. Identifying genes associated with growth and survival
      during infection should lead to a more comprehensive understanding of the ability
      of M. leprae to cause disease.

PMID- 15741742
TI  - Glomerular localization of erythropoietin receptor mRNA and protein in neonatal
      and mature mouse kidney.
AB  - BACKGROUND/AIMS: Erythropoietin (EPO) possesses well-established hematopoietic
      properties as the primary stimulator of red blood cell formation by binding to
      its receptor (EPO-R). Recent evidence suggests pathophysiological roles of EPO in
      several non-hematopoietic tissues including kidney. Our aim was to further
      clarify the glomerular localization of EPO-R in normal kidney, as well as changes
      in its expression during glomerulogenesis. METHODS: We analyzed EPO-R mRNA and
      protein expression in neonatal and adult mouse kidney by in situ hybridization
      and immunohistochemistry. To confirm the precise localization and developmental
      changes of EPO-R expression in podocytes in mature and developing glomeruli, we
      examined co-expression with the podocyte markers WT-1 and synaptopodin. RESULTS:
      In addition to tubular expression as reported recently, EPO-R expression was
      observed in podocytes as well as endocapillary cells in the glomeruli from adult
      mice. In newborn kidney, EPO-R mRNA and protein expression was first observed in
      developing podocytes in S-shaped bodies with expression subsequently increasing
      in glomeruli at the capillary-loop and maturing stages. Immunoelectron microscopy
      also demonstrated cytoplasmic expression of EPO-R that was prominent at the basal
      sides of podocytes in glomeruli at the late capillary-loop and maturing stage.
      CONCLUSION: EPO-R is expressed in developing and mature podocytes in mouse
      kidney, suggesting a possible role for EPO in podocyte biology.

PMID- 15741743
TI  - Effects of estrogen on muscarinic acetylcholine receptors in the rat hippocampus.
AB  - The aim of the present study was to investigate whether different estrogen
      manipulations have effects on the expression of muscarinic acetylcholine
      receptors (mAChRs) in the adult female rat hippocampus. Hippocampus was obtained
      from rats in proestrus (control), ovariectomized for 2, 10 and 15 days,
      ovariectomized for 15 days and treated with 17beta-estradiol for 7 days, and
      treated with 17beta-estradiol immediately after ovariectomy for 21 days. Rats'
      estrogen status was monitored by measuring estradiol plasma levels and uterus
      relative weight. [3H]quinuclidinyl benzilate ([3H]QNB) binding studies indicated
      that ovariectomy time-dependently increases the number of mAChRs in hippocampus
      when compared to those obtained from control rats. Estradiol treatments for 21
      days avoid the effect of ovariectomy. However, the estradiol treatments for 7
      days after 15 days of ovariectomy slightly change the number of mAChRs. In
      conclusion, these results showed that ovariectomy time-dependently increases
      mAChRs number in the rat hippocampus. In addition, these data suggest that
      treatment with estradiol initiated within a specific period of time after the
      loss of ovarian function may be effective at preventing specific effects of
      hormone deprivation on hippocampus.

PMID- 15741744
TI  - Differential stress reactivity in intact and ovariectomized prepubertal and adult
      female rats.
AB  - The pubertal development of the hypothalamic-pituitary-adrenal (HPA) axis has
      received relatively little experimental attention. As puberty is marked by an
      increase in the susceptibility to various psychiatric disorders that may be
      related to HPA dysfunction, it is imperative to elucidate the pubertal
      development of this neuroendocrine axis. To date, the limited research in this
      area has been conducted primarily on males. Presently, we investigated stress
      responsiveness, as measured by both stress hormones (e.g., corticotropin (ACTH)
      and corticosterone) and gonadal steroids, in intact and ovariectomized
      prepubertal and adult female rats before and after a 30-min session of restraint
      stress. We report here that intact prepubertal females exhibit an extended
      corticosterone stress response (30-45 min longer) compared to intact adults.
      Moreover, ovariectomized prepubertal females continue to exhibit a prolonged
      stress-induced corticosterone and progesterone response compared to
      ovariectomized adults, indicating these protracted responses prior to puberty are
      independent of ovarian hormones. ACTH levels were not significantly different
      between intact and ovariectomized prepubertal and adult animals at all the post
      stress time points measured, suggesting that the prolonged corticosterone
      response in prepubertal females is due to an enhanced sensitivity to ACTH at the
      level of the adrenal cortex. Taken together, these data indicate that stress
      reactivity changes dramatically during puberty in females. Furthermore, these
      data demonstrate additional development of the HPA axis during pubertal
      maturation, resulting in a more quickly terminated stress response in adulthood.

PMID- 15741745
TI  - How many cravings? Pharmacological aspects of craving treatment in alcohol
      addiction: a review.
AB  - In the last decade, craving has increasingly been considered an important target
      for the treatment of patients with alcohol problems, and several drugs able to
      interfere with the neurotransmitters involved in craving mechanisms have been
      experimented. However, different subtypes of patients could have different
      mechanisms at the basis of alcohol craving. In this review, the main drugs
      currently used in the treatment of patients with alcohol problems are described.
      A hypothesis of pharmacological treatment of the different types of craving is
      also discussed.

PMID- 15741746
TI  - Basal prolactin values correlate with response to reboxetine treatment in major
      depression, but not with response to citalopram.
AB  - Little is known about variables that might predict outcome in major depression.
      Recently, basal prolactin values (BPV) have been suggested to predict response to
      treatment with tricyclic antidepressive drugs. In order to examine whether BPV
      predict response to selective mono-aminergic therapy, 24 in-patients with major
      depression were treated in a single-masked, randomised study using the most
      selective noradrenergic or serotonergic reuptake inhibitors available for
      antidepressant treatment, i.e. reboxetine and citalopram. A significant
      correlation between BPV and treatment response to reboxetine was found, but not
      between BPV and response to citalopram. As BPV are influenced by noradrenergic
      activity, it can be hypothesized that depressed patients with comparatively high
      BPV have a relatively high noradrenergic function. This might explain why in our
      study depressed patients with the highest BPV responded strongest to selective
      noradrenergic treatment with reboxetine. As measurement of BPV is simple, further
      studies are suggested to examine the possible clinical value of the link between
      prolactin, noradrenergic function in major depression and treatment response.

PMID- 15741747
TI  - Plasma catecholamine levels after fluoxetine treatment in depressive patients.
AB  - It is known that selective serotonin reuptake inhibitors, widely used as
      antidepressive drugs, act by inhibiting the cell reuptake of serotonin, but their
      effect on the catecholaminergic system is not yet completely understood. In this
      study, we investigated plasma concentrations of norepinephrine, epinephrine and
      dopamine after acute and chronic administration of fluoxetine in depressive
      patients. Twelve patients affected by major depression received a single oral
      dose of fluoxetine in the morning, 5 mg in the first 5 days, 10 mg from the 6th
      to the 10th day and 20 mg from the 11th to the 40th day. Twelve healthy subjects
      received a placebo under identical testing procedures. Blood samples were
      collected at baseline and 7, 10 and 24 h after drug administration on the 1st day
      of fluoxetine administration at a dose of 5 mg, and on the 1st and the 30th day
      of fluoxetine administration at a dose of 20 mg (days 11 and 40 of treatment,
      respectively). We found that plasma norepinephrine, epinephrine and dopamine
      levels significantly increased after acute and chronic treatment (p < 0.001),
      reaching the highest concentrations on the last day. No significant changes of
      these parameters were observed in control patients.

PMID- 15741749
TI  - Relationship between disgust sensitivity, trait anxiety and brain activity during
      disgust induction.
AB  - We examined the influence of disgust sensitivity and trait anxiety on disgust
      processing via functional magnetic resonance imaging. Data of 63 healthy females
      were combined across four studies, where the same disgusting and affectively
      neutral pictures had been presented. The disgust pictures, rated as highly
      repulsive, provoked activation in the occipital cortex, the left prefrontal
      cortex and both amygdalae. Disgust sensitivity and trait anxiety were positively,
      and independently from each other, correlated with the activation of the right
      amygdala. This points to the role of the amygdala as an integrative brain
      structure, whose activation can be modulated by different affective styles.

PMID- 15741748
TI  - Dysregulated innate immune responses in young children with autism spectrum
      disorders: their relationship to gastrointestinal symptoms and dietary
      intervention.
AB  - OBJECTIVE: Our previous study indicated an association between cellular immune
      reactivity to common dietary proteins (DPs) and excessive proinflammatory
      cytokine production with endotoxin (lipopolysaccharide, LPS), a major stimulant
      of innate immunity in the gut mucosa, in a subset of autism spectrum disorder
      (ASD) children. However, it is unclear whether such abnormal LPS responses are
      intrinsic in these ASD children or the results of chronic gastrointestinal (GI)
      inflammation secondary to immune reactivity to DPs. This study further explored
      possible dysregulated production of proinflammatory and counter-regulatory
      cytokines with LPS in ASD children and its relationship to GI symptoms and the
      effects of dietary intervention measures. METHODS: This study includes ASD
      children (median age 4.8 years) on the unrestricted (n = 100) or elimination (n =
      77) diet appropriate with their immune reactivity. Controls include children with
      non-allergic food hypersensitivity (NFH; median age 2.9 years) on the
      unrestricted (n = 14) or elimination (n = 16) diet, and typically developing
      children (median age 4.5 years, n = 13). The innate immune responses were
      assessed by measuring production of proinflammatory (TNF-alpha, IL-1beta, IL-6,
      and IL-12) and counter-regulatory (IL-1ra, IL-10, and sTNFRII) cytokines by
      peripheral blood mononuclear cells (PBMCs) with LPS. The results were also
      compared to T-cell responses with common DPs and control T-cell mitogens assessed
      by measuring T-cell cytokine production. RESULTS: ASD and NFH PBMCs produced
      higher levels of TNF-alpha with LPS than controls regardless of dietary
      interventions. However, only in PBMCs from ASD children with positive
      gastrointestinal (GI(+)) symptoms, did we find a positive association between TNF
      alpha levels produced with LPS and those with cow's milk protein (CMP) and its
      major components regardless of dietary interventions. In the unrestricted diet
      group, GI(+) ASD PBMCs produced higher IL-12 than controls and less IL-10 than
      GI(-) ASD PBMCs with LPS. GI(+) ASD but not GI(-) ASD or NFH PBMCs produced less
      counter-regulatory cytokines with LPS in the unrestricted diet group than in the
      elimination diet group. There was no significant difference among the study
      groups with regard to cytokine production in responses to T-cell mitogens and
      other recall antigens. CONCLUSION: Our results revealed that there are findings
      limited to GI(+) ASD PBMCs in both the unrestricted and elimination diet groups.
      Thus our findings indicate intrinsic defects of innate immune responses in GI(+)
      ASD children but not in NFH or GI(-) ASD children, suggesting a possible link
      between GI and behavioral symptoms mediated by innate immune abnormalities.

PMID- 15741750
TI  - Season of birth in Danish children with language disorder born in the 1958-1976
      period.
AB  - Two preliminary studies have indicated a variation in season of birth in severely
      language-disordered children. In the current study, the season of birth in 472
      Danish children with language disorder born between 1958 and 1976 was compared
      with the season of birth of all Danish live-born children in the same period. For
      some part of the period (1964-1969), an excess of boys born in November was
      found. Particular attention was given to the inconsistent findings also found in
      language-related disorders like infantile autism and dyslexia and the choice of
      statistical method to determine seasonality.

PMID- 15741751
TI  - Central nervous effects of leptin and insulin on hippocampal leptin and insulin
      receptor expression following a learning task in Wistar rats.
AB  - Insulin and leptin are well known to be involved in the regulation of food intake
      and body weight. Recent studies have suggested that both hormones may also affect
      memory and learning processes. We explored whether the intrahippocampal
      administration of insulin or leptin improved spatial memory formation in rats
      following a radial maze task and whether the insulin and leptin receptor
      expression in different areas of the hippocampus was affected. Animals without a
      learning task were also investigated in order to differentiate between the
      influence of spatial learning and hormone application on receptor expression.
      Spatial memory formation was found unaltered following the different
      applications. The application of insulin increased the expression of the long
      form of the leptin receptor in the Ammon's horn and dentate gyrus region of the
      hippocampus in the learning group only. These data clearly show that learning is
      a prerequisite for the effect of insulin on leptin receptor expression.

PMID- 15741752
TI  - Brain glucocorticoid receptor and heat shock protein 70 levels in rats exposed to
      acute, chronic or combined stress.
AB  - The pattern and intensity of glucocorticoid receptor (GR) and heat shock 70
      protein (Hsp 70) changes in the hippocampus and brain cortex of adult Wistar rat
      males exposed to acute (immobilization, cold) and chronic (social isolation,
      crowding, daily swimming) stress or their combinations were followed by Western
      immunoblotting. Plasma ACTH and CORT were measured by chemiluminescent method and
      RIA. A significant decrease in cytosol GR and Hsp 70 was observed after acute
      stress, while chronic stresses led to negligible changes in both these proteins
      and caused a reduced responsiveness to a novel acute stress. This was valid
      irrespective of the type of chronic or acute stress combinations for both
      hippocampal and cortical GR and Hsp 70. The results support the hypothesis that
      chronic stress-induced deregulation of the LHPA axis may be caused, at least in
      part, by partial disruption of intracelullar negative feedback control in the
      higher centers of the brain.

PMID- 15741755
TI  - The aftermath of the concept of 'psychiatric comorbidity'.

PMID- 15741753
TI  - Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone
      alone in patients with hormone-refractory prostate cancer.
AB  - Satraplatin is a novel oral platinum (IV) complex that shows activity against
      hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor
      lines in phase I and phase II trials. A randomized multicenter phase III trial
      with a target sample size of 380 patients was initiated in men with HRPC. After
      50 randomized patients, the trial was closed to further accrual by the sponsoring
      company. An ad hoc analysis of all available data is reported here. Eligibility
      criteria included pathological proof of prostate cancer, documented progression
      despite prior hormonal manipulation, WHO PS 0-2, and no daily intake of narcotic
      analgesics. Patients were randomized between satraplatin 100 mg/m(2) for 5 days
      plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent.
      48/50 patients have progressed and 42 have died, mostly due to prostate cancer.
      Median overall survival was 14.9 months (95% CI: 13.7-28.4) on the satraplatin
      plus prednisone arm and 11.9 months (95% CI: 8.4-23.1) on prednisone alone
      (hazard ratio, HR = 0.84, 95% CI: 0.46-1.55). A >50% decrease in prostrate
      specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus
      prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free
      survival was 5.2 months (95% CI: 2.8-13.7) on the satraplatin plus prednisone arm
      as compared to 2.5 months (95% CI: 2.1- 4.7) on the prednisone alone arm (HR =
      0.50, 95% CI: 0.28-0.92). This difference is statistically significant (p =
      0.023). Toxicity was generally minimal in both arms. This randomized comparison
      of a combination of satraplatin and prednisone versus prednisone alone supports
      the antitumor activity of the combination. Its role in the treatment of HPRC
      remains to be elucidated in an appropriate phase III setting.

PMID- 15741754
TI  - Treatment with dehydroepiandrosterone prevents oxidative stress induced by 3
      nitropropionic acid in synaptosomes.
AB  - This study evaluates the antioxidative effect of dehydroepiandrosterone (DHEA)
      treatment on 3-nitropropionic acid (3-NPA)-induced oxidative stress in striatal
      and brain cortex synaptosomes. The oxidative derangement was confirmed by a high
      level of lipid peroxidation products and protein carbonyls, as well as by an
      enhanced superoxide dismutase activity (p < 0.001). These changes were partially
      prevented by DHEA. Moreover, 3-NPA induced a drop in succinate dehydrogenase
      activity, while DHEA treatment restored the succinate dehydrogenase activity.
      These results show that DHEA reduces oxidative stress in synaptosomes isolated
      from the brain of 3-NPA-treated rats, and they suggest this neurosteroid may
      protect mitochondrial and maintain synaptic integrity against damage induced by
      this acid.

PMID- 15741756
TI  - Postmyocardial infarction mortality in relation to depression: a systematic
      critical review.
AB  - The aim of this review was to survey the literature on depression in patients
      with myocardial infarction to assess the methodological quality and to test
      whether depression leads to an increased postmyocardial infarction mortality.
      Medline, Psycinfo, and www.UMI.com were searched, and researchers were contacted
      in the autumn of 2003. Thirty-one articles were reviewed. Only seven articles
      scored above a predefined level of 75% for acceptable quality. The articles lack
      description of non-responders, recall period for depressive symptoms, validation
      of applied instrument on target population, and sample size large enough to show
      differences between groups. The prevalence rates of depression ranged from 1.6 to
      50%. In eight articles, a diagnostic test was applied, in the rest of the
      studies, questionnaires were used. The prevalence of depression was highest in
      those using patient-completed questionnaires. A significant positive association
      was shown between depression and postmyocardial infarction mortality in 15
      studies, a non-significant association in 14, and in two articles, this was not
      reported. In articles with data collection starting after 1994, a non-significant
      relation tended to be reported. The studies were generally not of acceptable
      quality. They lacked sufficient power to show differences in stated end points
      between groups. Application of non-validated instruments caused large differences
      in prevalence rates of depression. Future studies should include a minimum of
      1,000 patients, use a validated instrument, re-examine the patients, and describe
      participants and non-participants in detail.

PMID- 15741757
TI  - Alexithymia, interhemispheric transfer, and right hemispheric specialization: a
      critical review.
AB  - BACKGROUND: One neural model of alexithymia relates the condition to poor
      interhemispheric transfer, while another model associates it with a disturbance
      in right hemisphere activity. METHODS: The available empirical evidence directly
      relating alexithymia to a deficit in interhemispheric transfer and/or in right
      hemisphere activity is critically reviewed. RESULTS: The interhemispheric
      transfer studies have related alexithymia to a deficit in transfer, but the
      nature and directionality of the transfer deficit have yet to be determined. Many
      of the hemispheric specialization studies do not relate alexithymia to a right
      hemisphere dysfunction. Shortcomings of these studies are reviewed. CONCLUSIONS:
      The hypothesis that alexithymia is related to a deficit in the right-to-left
      transfer of emotional information and to a right hemisphere impairment in emotion
      processing remains to be tested directly and definitively. Suggestions for future
      research are made.

PMID- 15741758
TI  - Using interaction graphs for analysing the therapy process.
AB  - BACKGROUND: Therapy processes are complex dynamical systems where several
      variables are constantly interacting with each other. In general, the underlying
      mechanisms are difficult to assess. Our approach is to identify the dependency
      structure of relevant variables within the therapy process using interaction
      graphs. These are instruments for multivariate time series which are based on the
      analysis of partial spectral coherences. We used interaction graphs in order to
      investigate the therapy process of a multimodal therapy concept for fibromyalgia
      patients. Our main hypothesis was that self-efficacy plays a central role in the
      therapy process. METHODS: Patients kept an electronic diary for 13 weeks. Pain
      intensity, depression, sleep quality, anxiety and self-efficacy were assessed via
      visual analogue scales. The resulting multivariate time series were aggregated
      over individuals, and partial spectral coherences between each pair of the
      variables were calculated. From the partial coherences, interaction graphs were
      plotted. RESULTS: Within the resulting graphical model, self-efficacy was
      strongly related to pain intensity, depression and sleep quality. All other
      relations were substantially weaker. There was no direct relationship between
      pain intensity and sleep quality. CONCLUSIONS: The relations between two
      variables within the therapy process are mainly induced by self-efficacy.
      Interaction graphs can be used to pool time series data of several patients and
      thus to assess the common underlying dependency structure of a group of patients.
      The graphical representation is easily comprehensible and allows to distinguish
      between direct and indirect relationships.

PMID- 15741759
TI  - Use of the diagnostic criteria for psychosomatic research in oncology.
AB  - BACKGROUND: Psycho-oncology literature has shown that 30-50% of cancer patients
      meet the criteria for a psychiatric diagnosis, according to the usual nosographic
      classification (e.g. DSM). The Diagnostic Criteria for Psychosomatic Research
      (DCPR) have been shown to be useful in identifying psychological constellations
      in patients with medical illness. The aims of the study were to compare the DSM
      IV and the DCPR in their application to cancer patients. METHOD: One hundred and
      forty-six patients with cancer underwent semistructured interviews to assess
      psychiatric morbidity and psychosocial syndromes according to the DSM-IV and the
      DCPR, respectively. The Brief Symptom Inventory (BSI) was also used to assess
      psychological stress symptoms. RESULTS: Sixty-five subjects (44.5%) met the
      criteria for a DSM-IV diagnosis (DSM cases), while 104 patients (71.2%) presented
      symptoms meeting the criteria for at least one DCPR syndrome. Three DCPR
      dimensions were more frequent than others, specifically Health Anxiety (37.7%),
      Demoralization (28.8%) and Alexithymia (26%). Among the subjects with no formal
      DSM-IV diagnosis (n = 81), 58% had at least one DCPR syndrome. DSM-IV cases had
      higher scores on several BSI subscales in comparison with patients with only one
      DCPR syndrome, while no difference was found in patients with more than one DCPR
      diagnosis. CONCLUSIONS: The DCPR system was found to be useful in oncology in
      investigating psychological conditions which are not identified by the DSM-IV
      alone. Assessment of more specific constructs, other than intensity of general
      stress symptoms, may give more specific information and help in tailoring
      psychological intervention for patients with cancer.

PMID- 15741760
TI  - Mindfulness-based stress reduction as an adjunct to outpatient psychotherapy.
AB  - BACKGROUND: Research on Mindfulness-Based Stress Reduction (MBSR) has supported
      the utility of the technique in a number of clinical settings. This study
      explored whether MBSR, used as an adjunct to individual psychotherapy, would
      result in more rapid alleviation of symptoms, increased achievement of
      therapeutic goals, and a decrease in number of therapy sessions sought by
      clients. METHODS: A group undergoing psychotherapy coupled with training in MBSR
      was compared with a group undergoing psychotherapy alone. RESULTS: At the
      conclusion of MBSR training, the groups showed a comparable significant decrease
      in psychological distress. However, the MBSR group's gains on a novel measure of
      goal achievement were significantly greater than those of the comparison group.
      In addition, the MBSR group terminated therapy at a significantly greater rate
      than the comparison group. CONCLUSION: The effects of introducing MBSR early in
      psychotherapy, as well as its effect on self-directed goal attainment in non
      psychotherapy contexts, deserve further attention.

PMID- 15741762
TI  - Assessing the community prevalence of bipolar spectrum symptoms by the mood
      disorder questionnaire.
AB  - BACKGROUND: The goal of this study was to assess the frequency and spectrum of
      symptoms related to bipolar disorders in a community sample by means of a self
      rating questionnaire. METHOD: The Mood Disorder Questionnaire, a self-rating
      scale which evaluates DSM-IV manic/hypomanic symptoms, was administered to a
      community sample of 1,034 individuals recruited through advertisements. Symptom
      interrelationships were studied by factor analysis. RESULTS: 275 individuals
      (26.6%) reported moderate or severe impairment due to the symptoms.
      Manic/hypomanic symptoms were present in a high proportion of individuals. Factor
      analysis found a two-factor structure of bipolar spectrum symptoms (an elevated
      mood overactivity factor, and an irritable behavior factor). CONCLUSION: The
      findings of this study highlight the need of complementing clinical
      investigations on the bipolar spectrum with community studies. Subclinical manic
      hypomanic symptoms may be present also in allegedly unipolar patients and may
      have implications on the course of illness.

PMID- 15741761
TI  - Persistent cognitive dysfunctions in bipolar I disorder and schizophrenic
      patients: a 3-year follow-up study.
AB  - BACKGROUND: Neurocognitive impairment has consistently been considered a central
      and stable feature in schizophrenia. As this possibility has been far less
      studied in bipolar disorder, we aimed to prospectively investigate the stability
      and specificity of cognitive performance in bipolar disorder compared to
      schizophrenia. METHODS: Fifteen DSM-IV bipolar type I patients and 15
      schizophrenic patients were assessed twice with a comprehensive
      neuropsychological battery and the Positive and Negative Syndrome Scale over a 3
      year follow-up. The cognitive performance of the groups was compared at baseline
      and 3 years later as a mean with that of 26 healthy volunteers. Endpoint and
      baseline assessments were also compared for each patient group in order to
      evaluate the stability of cognitive impairment. RESULTS: At both time points,
      bipolar and schizophrenic patients showed significant deficits on most of the
      cognitive tasks compared to healthy subjects. Overall, the cross-sectional
      cognitive profile was similar for both patient groups. Moreover, after
      controlling for age and length of illness, the two groups' cognitive function did
      not differ over time in any test. With the exception of the Stroop color-word
      interference task, performance at baseline for each test but neither length of
      illness nor diagnostic category predicted the endpoint performance. CONCLUSION:
      This preliminary study suggests that cognitive impairment is also mainly stable
      over time in bipolar I disorder and thus not specific to schizophrenia.

PMID- 15741763
TI  - Increased maintenance of obsessive-compulsive disorder remission after integrated
      serotonergic treatment and cognitive psychotherapy compared with medication
      alone.
AB  - BACKGROUND: Both medication and psychotherapy are effective in obsessive
      compulsive disorder (OCD). However, they both have disadvantages. We aimed at
      studying the long-term effectiveness of integrated treatment compared with
      medication alone. METHODS: A private practice sample of 20 consecutive patients
      with OCD (DSM-III-R) who achieved remission or marked improvement [Yale-Brown
      Obsessive-Compulsive Scale (YBOCS) score < or =10 and Global Assessment of
      Functioning (GAF) scale score > or =70] after drug treatment (clomipramine or
      selective serotonin reuptake inhibitors for 12-24 months) with or without
      concurrent cognitive psychotherapy were followed up. In the integrated treatment
      group, psychotherapy was started on the second or third visit and was timed to
      end after medication. Efforts were applied to integrate treatments within a
      biopsychosocial theoretical framework. As randomisation was not feasible in the
      study setting, treatment allocation was based on patients' preference. Patients
      were assessed before treatment, after treatment and at each follow-up contact
      with the YBOCS, the Hamilton Depression Rating Scale, and the GAF scale. Kaplan
      Meier survival analysis was performed on the time to OCD relapse. RESULTS: Of the
      factors studied (gender, age, duration of disorder, severity of OCD symptoms at
      baseline), only treatment was associated with outcome. Of 10 patients treated
      with medication alone, 8 relapsed. Of 10 patients who received integrated
      treatment, only 1 relapsed. The estimated mean survival time was significantly
      higher (p < 0.001) in the integrated treatment group (132 months, 95% CI 107-157)
      than in the medication group (25 months, 95% CI 12-38). CONCLUSIONS: Although our
      results need confirmation by further, more robust studies, the long-term
      superiority of integrated treatment over medication alone was large. Patients
      with OCD might have viable options other than long-term drug treatment.

PMID- 15741764
TI  - Personality characteristics of psychiatric trainees.

PMID- 15741766
TI  - Immunohistochemical expression of vascular endothelial growth factor and
      microvessel counting as prognostic indicators in node-negative colorectal cancer.
AB  - This manuscript reports a carefully controlled study of patients with Dukes B
      colorectal cancer (Dukes stage A, n=12 and Dukes stage B, n=44).
      Immunohistochemistry has been used to demonstrate reactivity for vascular
      endothelial growth factor (VEGF), and to measure levels of microvessel density
      (MVD) in order to assess the relationship of tumor angiogenesis with clinical
      outcome. Immunohistochemistry was performed using antibodies to VEGF and CD34
      (for intratumoral vessel identification) and counting was performed at the
      invasive margin of the tumor. Results showed that for Dukes stage A patients 4/12
      died of their disease, none of whose tumor was VEGF positive. In contrast, 2
      patients who survived were positive for VEGF cytoplasmically, but neither showed
      increased tumor MVD. In Dukes B patients 10/44 died, 5 of whose tumor
      demonstrated VEGF reactivity, both in malignant cells and in tumor vascular
      endothelium. MVD ranged from 11 to 53 (median 28) for Dukes A cases and from 9 to
      69 (median 32.5) for the Dukes B group. Kaplan-Meier plots and log rank test
      statistics for Dukes B patients demonstrated that VEGF reactivity in cells, and
      in tumor vascular endothelium was correlated with survival (p=0.047 and p < or =
      0.06, respectively). There was a significant relationship between the presence of
      VEGF reactivity on vascular endothelium and outcome by Fisher's exact test
      (p=0.018). Similarly, by the same test VEGF positivity was significantly
      correlated with patient mortality (p=0.032). The presence of endothelial VEGF
      reactivity correlated with VEGF in malignant cells (p=0.0001) by Mann-Whitney U
      test and a significant inverse relationship between vessel density and patient
      survival was demonstrated (p = 0.019). The finding that in Dukes B patients MVD
      was inversely correlated with mortality supports the hypothesis that a low
      microvascular count is predicted close to the invasive margin, where VEGF
      expression is upregulated in response to hypoxia, induced by a lack of a
      functional vasculature. These data will be used to identify cohorts of patients
      who have a high risk of relapse and can be selected for adjuvant therapies such
      as VEGF antibody or antitumor antibody-directed therapy.

PMID- 15741765
TI  - Characterization of HER1 (c-erbB1) status in locally advanced breast cancer using
      fluorescence in situ hybridization and immunohistochemistry.
AB  - Epidermal growth factor receptor (EGFR) is a 170-kDa transmembrane glycoprotein
      encoded by the HER1 protooncogene, located at 7p12. This receptor is related to
      the pathogenesis of breast cancer. The aim of this study was to analyze the
      status of HER1 using fluorescence in situ hybridization (FISH) and
      immunohistochemistry in a series of 48 patients with locally advanced breast
      cancer (LABC). Before neoadjuvant chemotherapy, core biopsies were taken from
      patients with LABC and were processed into paraffin blocks. Biopsies were then
      studied using FISH with a HER1 probe (Vysis, Downers Grove, Ill., USA). They were
      also analyzed immunohistochemically using two different EGFR antibodies from
      DakoCytomation (Denmark, A/S) and from Zymed (San Francisco, Calif., USA). HER1
      amplifications were not found, although 31% of the cases presented aneusomy of
      chromosome 7. Only 2 cases presented EGFR expression. LABC presented a low level
      of EGFR expression. HER1 amplification was not present in LABC, although the
      polysomy of chromosome 7 was a common finding.

PMID- 15741767
TI  - Possible involvement of adipocyte-derived leucine aminopeptidase via angiotensin
      II in endometrial carcinoma.
AB  - OBJECTIVE: It has recently been appreciated that a local autocrine or paracrine
      renin-angiotensin system (RAS) may exist in a number of tissues. Angiotensin II
      (AngII) is a potent RAS-derived vasoconstrictor peptide, and it is involved in
      tumor angiogenesis. We have cloned human adipocyte-derived leucine aminopeptidase
      (A-LAP), which degrades Ang II. This study investigated whether the expression of
      A-LAP, Ang II, angiotensin type I receptor (AT1R) and vascular endothelial growth
      factor (VEGF) correlates with clinicopathologic factors and prognosis in patients
      with endometrial endometrioid adenocarcinoma. METHODS: Histologic sections of
      formalin-fixed, paraffin-embedded specimens from 94 primary endometrial
      carcinomas were stained for A-LAP, AngII, AT1R and VEGF using each antibody.
      Disease-free survival (DFS) and other clinicopathologic characteristics were
      analyzed according to the intensity of each staining. RESULTS: Of 94 cases, 91
      (96.8%) showed specific A-LAP immunostaining. A-LAP expression demonstrated
      negative correlations with myometrial invasion (p = 0.01) and vascular
      infiltration (p = 0.01). Of 94 cases, 77 (81.9%) showed specific AngII
      immunostaining. We found a positive correlation between AngII expression and
      surgical stage (p = 0.01). Of 94 cases, 56 (59.6%) showed specific AT1R
      immunostaining and 73 (77.7%) specific VEGF immunostaining. We found a positive
      correlation between VEGF expression and lymph node metastasis (p = 0.05). AngII
      and AT1R expression predicted a significantly poorer prognosis. Contrarily, A-LAP
      expression indicated a significantly more favorable prognosis in endometrial
      endometrioid adenocarcinoma patients. Multivariate analysis demonstrated that A
      LAP expression (odds ratio, 0.12; 95% confidence interval, 0.025-0.618; p = 0.01)
      was an independent prognostic factor. CONCLUSIONS: In this study, we demonstrated
      the existence of local RAS and A-LAP in endometrial endometrioid adenocarcinoma
      as prognostic predictors of clinical outcome. These findings suggest that the
      assessment of RAS and A-LAP status provides clinically useful prognostic
      information in patients with endometrial carcinoma.

PMID- 15741768
TI  - Experimental study of human expressed sequences newly identified in silico as
      tumor specific.
AB  - In our previous studies, we used global computational differential display of
      ESTs that belong to UNIGENE clusters and identified human sequences
      differentially expressed in human tumors, as well as a considerable amount of
      transcripts represented only in tumor-derived cDNA libraries. Most of the tumor
      specific EST clusters are derived from the plurality of the tumor types
      originated in tissues of both ectodermal and mesodermal origin. We found that
      many of such tumor-specific ESTs do not contain long open reading frames and
      cannot be classified as protein-encoding genes. To experimentally assess patterns
      of expression of these EST clusters, we studied four of them in PCR experiments
      on Clontech MTC panels. The experimental data confirm the results obtained by in
      silico screening, i.e. tumor specificity of their expression. We suggest that a
      significant increase in the expression of non-coding RNA is a fundamental feature
      of cancer cells, and that such transcripts could serve as markers for the
      diagnosis or monitoring of human malignancies.

PMID- 15741769
TI  - Minimizing the immunogenicity of antibodies for clinical application.
AB  - The clinical utility of murine monoclonal antibodies has been greatly limited by
      the human anti-murine antibody responses they effect in patients. To make them
      less immunogenic, murine antibodies have been genetically engineered to
      progressively replace their murine content with that of their human counterparts.
      This review describes the genetic approaches that have been used to humanize
      murine antibodies, including the generation of mouse-human chimeric antibodies,
      veneering of the mouse variable regions, and the grafting of murine
      complementarity-determining regions (CDRs) onto the variable light (VL) and
      variable heavy (VH) frameworks of human immunoglobulin molecules, while retaining
      only those murine framework residues deemed essential for the integrity of the
      antigen-binding site. To minimize the anti-idiotypic responses that could still
      be evoked by the murine CDRs in humanized antibodies, two approaches have also
      been described. These are based on grafting onto the human frameworks the
      'abbreviated' CDRs or only the specificity-determining residues (SDRs), the CDR
      residues that are involved in antigen interaction. The SDRs are identified
      through the help of the database of three-dimensional structures of
      antibody:antigen complexes or by mutational analysis of the antibody-combining
      site. In addition, we also describe the use of in vitro affinity maturation to
      enhance the binding affinity of humanized antibodies, as well as the manipulation
      of framework residues to maximize their human content and minimize their
      immunogenic potential.

PMID- 15741770
TI  - Cardiovascular effects of fine and ultrafine particles.
AB  - Epidemiological studies of the past decades have provided a strong body of
      evidence that elevated levels of ambient particulate air pollution (PM) are
      associated with increased cardiovascular and respiratory morbidity and mortality.
      Exacerbations of ischemic and/or arrhythmic cardiac diseases have been linked to
      PM exposure. At a workshop held at the GSF- National Center for Environment and
      Health in November 2003, relevant epidemiological and toxicological data of the
      past 5 years were compiled and potential biological pathways discussed. Available
      clinical and experimental evidence lends support to the following mechanisms
      mediating cardiovascular effects of inhaled ambient particles: (i) pulmonary
      and/or systemic inflammatory responses inducing endothelial dysfunction, a pro
      coagulatory state and promotion of atherosclerotic lesions, (ii) dysfunction of
      the autonomic nervous system in response to direct reflexes from receptors in the
      lungs and/or to local or systemic inflammatory stimuli, and (iii) cardiac
      malfunction due to ischemic responses in the myocardium and/or altered ion
      channel functions in myocardial cells. While an increasing number of studies
      addressing these questions support the notion that PM exposure is associated with
      cardiovascular effects, these studies at present provide only a fragmentary and
      at times inconclusive picture of the complex biological pathways involved. The
      available data are consistent with the occurrence of a systemic inflammatory
      response and an alteration of autonomic cardiac control, but evidence on
      endothelial dysfunction, pro-coagulatory states, and PM-related myocardial
      malfunction is as yet scarce. Further studies are therefore needed to
      substantiate our current understanding of the pathophysiological links between PM
      exposure and adverse cardiovascular outcomes.

PMID- 15741771
TI  - Dose delivery late in the breath can increase dry powder aerosol penetration into
      the lungs.
AB  - In addition to aerosol particle size and mode of inhalation, the time-point of
      dose delivery during inhalation may be an important factor governing the
      intrapulmonary distribution of aerosolized drug. To generate different
      intrapulmonary deposition patterns of a drug model aerosol, a device with the
      capability of delivering small amounts of technetium-99m-labeled lactose dry
      powder at pre-set time-points during inhalation was developed. A single dose of
      the radioaerosol was delivered after inhalation of 20% (A) or 70% (B) of the
      vital capacity inhaled through the device. Twelve healthy subjects were studied
      in a randomized crossover fashion. Planar gamma scintigraphy was carried out, and
      the penetration index, PI, defined as the ratio of peripheral to central lung
      zone deposition of radioactivity, was estimated. A significant increase in PI
      from 3.0 (A) to 3.7 (B) was observed with the change from early to late delivery
      of the dose (p < 0.01). No difference in the total amount of radioactivity within
      the lungs could be detected. In conclusion, independent of total pulmonary
      deposition, deeper dry powder aerosol penetration into the lungs was found for
      the dose delivered at near end instead of at the beginning of inhalation. By
      computational modeling of the aerosol transport and deposition, that finding was
      mechanistically explained by differences in airway caliber as a consequence of
      the level of lung inflation at the time-point of dose delivery.

PMID- 15741772
TI  - Gamma scintigraphic evaluation of a miniaturized AERx pulmonary delivery system
      for aerosol delivery to anesthetized animals using a positive pressure
      ventilation system.
AB  - The purpose of this study was to characterize performance of a miniaturized
      AERx((R)) Pulmonary Delivery System designed for aerosol administration to large
      animal models. The miniaturized AERx System was developed through a systematic
      scaling down of the AERx System used for humans to allow for operation in certain
      animal models with lower inspiratory flow rates and inhaled volumes than those
      used for humans. We used gamma scintigraphy to characterize the in vivo particle
      deposition achieved with the miniaturized AERx System in two dogs. The dogs were
      3-4 years old, and weighed 10.4 kg and 13.6 kg. Acepromazine was used as pre
      anesthetic medication. Anesthesia was induced with 5% isoflurane. The trachea was
      intubated using an endotracheal tube (internal diameter 8.5 mm), and the dogs
      were ventilated using positive pressure during the exposure using the LRRI puff
      generator. An inhalation of aerosol was initiated by activation of the puff
      generator though the computer-controlled interface. Each dog inhaled
      approximately 0.8 L per puff, of which the aerosol volume comprised approximately
      0.25 L, at a target flow rate of 15 L/min. The dogs were exposed to 10 AERx
      Strips in 10 puffs. The mass median aerodynamic diameter of the aerosolized
      formulation was approximately 1.25 microm with a fine particle fraction <3.5
      microm of 0.976. The scintigraphic images showed uniform bilateral lung
      deposition following aerosol delivery with the AERx System. Total lung deposition
      for the two dogs was 10.7% and 18% of the loaded dose from the AERx Strip. The
      corresponding peripheral lung: inner lung (P/I) ratios were 0.83 and 0.75,
      suggestive of deposition in the deep lung. Only 0.1% to 0.2% of the loaded dose
      was exhaled. These results show the miniature AERx System can efficiently deliver
      aerosols to the deep lung of dogs. The miniaturized AERx System would be a
      valuable tool for conducting proof-of-concept studies as well as safety and
      tolerability analysis of inhaled drug candidates in large animal models.

PMID- 15741773
TI  - Optimum peripheral drug deposition in patients with cystic fibrosis.
AB  - In order to identify the optimum particle size and breathing pattern for high
      peripheral deposition of inhaled drugs in patients with cystic fibrosis, regional
      deposition in these patients was studied systematically as a function of particle
      size, inhalation volume and flow rate. Regional deposition was assessed using the
      single-breath regional deposition technique in which the concentration profile of
      inhaled and exhaled non-radioactive, monodisperse test particles is analyzed.
      Using this technique particle deposition within the functional dead space volume
      and peripherally can be assessed. Regional deposition was measured in 12 patients
      with cystic fibrosis using 2, 3, 4, and 5.5 microm particles, inhalation volumes
      of 500, 1000, 1500, and 2000 cm(3), and inhalation flow rates of 100, 250, 500,
      and 750 cm(3)/sec. Peripheral deposition was highest when 2-3-microm particles
      were inhaled with air-flow rates of 250-500 cm(3)/sec. With these parameters
      peripheral deposition increased with increasing inhalation volume and reached
      values of about 60% of the total drug inhaled. It has been shown that high
      peripheral drug deposition can be achieved in patients with CF when inhalations
      are performed using an optimized combination of particle size and breathing
      pattern.

PMID- 15741774
TI  - A prototype prophylactic anti-influenza preparation in aerosol form on the basis
      of Abies sibirica polyprenols.
AB  - This research investigates a promising antiviral compound based on polyprenols
      from Siberian silver fir (Abies sibirica). The physico-chemical characteristics
      of a preparation developed in aerosol form and an estimation of its protective
      efficacy against aerosol challenge of laboratory animals are presented. It is
      shown that (1) by using a simple ultrasonic disperser one can obtain aerosol of
      three formulations studied with about 70% of its mass accumulated in the size
      range below 1.8 microm; (2) 40-100% of aerosol particles contain preparation for
      different formulations; (3) after delivering under specified schedules, the
      preparations as developed can protect up to 100% of mice against 5 LD(50) of
      influenza A/Aichi/2/68 (H3N2) virus aerosol infection. Animals inhaled twice the
      preparation doses (which were 100 times lower than injection ones of the same
      efficacy) and did not exceed 10 microg/mouse. It was shown that the mode of
      action of this immunomodulating preparation was nonspecific stimulation of immune
      cells' various activities.

PMID- 15741775
TI  - Formoterol delivered via a new multi-dose dry powder inhaler (Certihaler) is as
      effective and well tolerated as the formoterol dry powder inhaler (Aerolizer) in
      children with persistent asthma.
AB  - The Certihaler is a new multi-dose dry powder inhaler for the delivery of
      formoterol (Foradil), a long-acting beta(2)-agonist. This dose-ranging study
      compared the efficacy and safety of formoterol 5, 10, 15 and 30 microg and
      placebo administered via the Certihaler or formoterol 12 microg via a single-dose
      dry powder inhaler (Aerolizer) in children with persistent asthma. This was a
      randomized, placebo-controlled, double-blind, double-dummy, incomplete block
      crossover, dose-finding and pharmacokinetic study. Children (5-12 years, n = 77)
      received four of the active treatments twice weekly (BID) for 1 week separated by
      1-week single-blind washouts. The primary efficacy variable was 12-h AUC of
      FEV(1) after 1 week's treatment. Secondary variables included serial 12-h FEV(1).
      A subset of patients (n = 37) participated in a pharmacokinetic analysis. All
      formoterol doses resulted in significant increases in 12-h AUC of FEV(1) compared
      with placebo, and there was no difference between active treatments. The onset of
      action of formoterol was <3 min for all active treatments. Doses of formoterol >
      or =10 microg via the Certihaler increased FEV(1) significantly for up to 12 h
      compared with placebo. The 5 microcg dose via the Certihaler and 12 microg dose
      via the Aerolizer had a significant effect up to 8 and 7 h post-dose,
      respectively. Urinary excretion of formoterol via the Certihaler increased in a
      dose-proportional manner. All formoterol doses were well tolerated, but some
      patients experienced tremor at the 15 and 30 microg doses. Despite the lack of
      significant differences between the active doses in the overall bronchodilation,
      formoterol 10 microg BID via the Certihaler was the dose that provided the best
      balance between efficacy and tolerability: its duration of action was sustained
      over 12 h, contrary to that the lower dose (5 microg BID), whereas its
      tolerability, especially with regard to tremor, was better than the higher doses
      (15 and 30 microg BID). Overall, Certihaler 10 microg BID was not significantly
      different from formoterol 12 microg BID via Aerolizer.

PMID- 15741776
TI  - Ventolin Diskus and Inspyril Turbuhaler: an in vitro comparison.
AB  - Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs),
      pulmonary deposition, and the biological effects depend on drug formulation and
      device and patient characteristics. The aim of this study was to measure, in
      vitro, the relationship between parameters of inhalation profiles recorded from
      patients, the TED and fine particle mass (FPM) of Diskus and Turbuhaler inhalers.
      Inhalation profiles (IPs) of 25 patients, a representative sample of a wide range
      of 1500 IPs generated by 10 stable asthmatics, 3 x 16 (mild/moderate/severe) COPD
      patients and 15 hospitalized patients with an exacerbation asthma or COPD, were
      selected for each device. These 25 IPs were input IPs for the Electronic Lung (a
      computerdriven inhalation simulator) to determine particle size distribution from
      Ventolin Diskus and Inspyril Turbuhaler. The TED and FPM of Diskus and FPM of
      Turbuhaler were affected by the peak inspiratory flow (PIF) and not by slope of
      the pressure-time curve, inhaled volume and inhalation time. This flow-dependency
      was more marked at lower flows (PIF < 40 L/min). Both the TED and FPM of Diskus
      were significantly higher as compared to those of the Turbuhaler [mean (SD)
      TED(_diskus) (%label claim) 83.5 (13.9) vs. TED(_turbuhaler) (72.5 (11.1) (p =
      0.004), FPM(_diskus) (%label claim) 36.8 (9.8) vs FPM(_turbuhaler) (28.7 (7.7) (p
      < 0.05)]. The TED and FPM of Diskus and FPM of Turbuhaler were affected by PIF,
      the flow-dependency being greater at PIF values below 40 L/min. Lower PIFs
      occurred more often when using Turbuhaler than Diskus, since Turbuhaler have a
      higher resistivity, requires substantially higher pressure in order to generate
      the same flow as Diskus. TED, dose consistency and the FPM were higher for Diskus
      as compared to Turbuhaler. The flow dependency of TED and FPM was substantially
      influenced by inhalation profiles when not only profiles of the usual outpatient
      population were included but also the real outliers from exacerbated patients.

PMID- 15741778
TI  - Psychopharmacology news.

PMID- 15741779
TI  - Managed care. Crossroads.

PMID- 15741780
TI  - Recent child pharmacoepidemiological findings.

PMID- 15741781
TI  - Pharmacoepidemiology and pediatric psychopharmacology research.

PMID- 15741782
TI  - Concomitant pharmacotherapy among youths treated in routine psychiatric practice.
AB  - OBJECTIVES: The aim of this study was to assess rates and correlates of
      concomitant pharmacotherapy in children and adolescents treated by psychiatrists
      in a broad range of clinical settings. METHODS: Cross-sectional data on 392 child
      and adolescent patients aged 2-17 years from the 1997 and 1999 American
      Psychiatric Practice Research Network Study of Psychiatric Patients and
      Treatments were used, and weighted estimates are provided. RESULTS: Findings
      indicate that 84% of child and adolescent patients received one or more
      psychopharmacologic medications; 52% of patients treated with medications
      received concomitant pharmacotherapy (i.e., two or more medications). Patients
      who were treated with psychopharmacologic treatments received a median of 2
      medications (range, 1-6). Highest rates of concomitant pharmacotherapy were among
      patients with bipolar disorder (87%). Correlates of concomitant pharmacotherapy
      included: (1) having a diagnosis of bipolar disorder, (2) having co-occurring
      Axis I or II disorders or general medical conditions, and (3) currently receiving
      treatment in an inpatient setting. CONCLUSIONS: Over 40% of child and adolescent
      patients of psychiatrists were prescribed two or more psychopharmacologic
      medications. Patients with chronic and clinically complex conditions were more
      likely to receive concomitant pharmacotherapy. Most often, efficacy of U.S. Food
      and Drug Administration (FDA)-approved medications has been examined as
      monotherapy, and cautions on drug interactions and off-label use derived from
      multiple sources accompany each product. With high rates of concomitant
      pharmacotherapy among children and adolescents in psychiatric care, additional
      research on efficacy and safety of this treatment strategy is necessary.

PMID- 15741783
TI  - Trends in use of antidepressants, lithium, and anticonvulsants in Kaiser
      Permanente-insured youths, 1994-2003.
AB  - In view of the current controversy regarding the use of antidepressants in
      children and adolescents, we examined trends from 1994 to 2003 in the use of
      antidepressants, lithium, and anticonvulsants by enrollees, aged 5-17 years, of
      Kaiser Permanente in Northern California. We found that the use of
      antidepressants more than doubled from 9.4 per 1000 enrollees to 21.3 per 1000.
      Most of this increase is associated with selective serotonin reuptake inhibitors
      (SSRIs), which increased from 4.6 to 14.5 per 1000. The use of tricyclic
      antidepressants (TCAs) decreased markedly, while the increase of other newer
      antidepressants rose from 1.3 to 6.5 per 1000. The use of anticonvulsants nearly
      doubled, from 3.5 to 6.9 per 1000, while lithium use was relatively stable at a
      rate of nearly 1 per 1000. Use of SSRIs, newer antidepressants, and
      anticonvulsants increased in boys as well as girls in each of three age groups: 5
      9, 10-14, and 15-17 years. An increasing percentage of the antidepressant users
      had a diagnosis of depression, and an increasing percentage of anticonvulsant
      users had a diagnosis of bipolar disorder. Although the safety and efficacy of
      antidepressants in youths needs to be more firmly established, these findings may
      reflect progress in the diagnosis and treatment of mental illness.

PMID- 15741784
TI  - Psychotropic co-medication among stimulant-treated children in The Netherlands.
AB  - OBJECTIVES: The aim of this study was to examine stimulant use from 1998 to 2002
      among children in the Dutch pediatric population with emphasis on psychotropic co
      medication. METHODS: A drug utilization study was based on community pharmacy
      dispensing data from 1998 to 2002 for children aged 0-19 years in the northern
      and eastern part of The Netherlands. RESULTS: The prevalence of stimulant use
      increased from 0.6% in 1998 to 1.2% in 2002. Duration of stimulant treatment was
      longest in children aged 5-14 years. The use of any psychotropic co-medication in
      stimulant users increased from 12% in 1998 to nearly 15% in 2002. Of those youths
      who were prescribed stimulant medication in 2002, the most co-prescribed class
      was the antipsychotics (7.9%). In 1998, none of the stimulant-treated children
      received antidepressants for co-medication; in 2002, this was 1.8%. CONCLUSION:
      The prevalence of stimulant use among children in The Netherlands has increased
      in recent years, mainly as a result of the duration of stimulant treatment.
      Psychotropic co-medication among stimulant-treated children increased moderately.

PMID- 15741785
TI  - Medication patterns for attention-deficit/hyperactivity disorder and comorbid
      psychiatric conditions in a low-income population.
AB  - The aims of this study were two-fold: (1) to describe the patterns of comorbid
      psychiatric diagnosis and psychotropic drug therapy for children enrolled in a
      Medicaid-managed care program and diagnosed with attention-deficit/hyperactivity
      disorder (ADHD) in 2000 and (2) to examine child and provider characteristics
      associated with psychotropic medication patterns for this population.
      Multivariate logistic regression models were used to examine correlates of
      stimulant and seven nonstimulant psychotropic medication classes (alpha-agonists,
      mood stabilizer/anticonvulsant, antianxiety, standard antipsychotic, atypical
      antipsychotic, and tricyclic antidepressant (TCA)/other antidepressant and
      selective serotonin reuptake inhibitor (SSRI) antidepressant). With the exception
      of conduct disorders (odds ratio, 1.22; 95% confidence interval, 1.06-1.40),
      comorbid disorders had a significant protective effect (odds ratio less than 1)
      on dispensing stimulants. After adjusting for covariates, stimulant dispensing
      was strongly correlated with the interactions of geographic region with
      race/ethnicity and provider type. Children residing in the upstate New York
      region had an approximately ten-fold greater chance of being dispensed a
      stimulant compared to similar children in New York City. Utilizing a mental
      health provider increased the chance of being dispensed a stimulant by factor of
      two for children from New York City of any race/ethnicity group. Models
      predicting nonstimulant drug dispensing were distinct from the stimulant model.
      After adjusting for covariates, nonstimulant psychotropic medication dispensing
      was correlated with clinical factors, including comorbid disorder category and
      use of a mental health provider, as well as notable sociodemographic factors.
      Complex psychotropic medication and comorbid psychiatric disorder patterns were
      evident for this low-income population of children with ADHD. The roles of
      clinical, patient, and provider factors need to be better understood to explain
      these patterns of stimulant and nonstimulant psychotropic medications dispensed.

PMID- 15741786
TI  - Current prescribing patterns in outpatient child and adolescent psychiatric
      practice in central New York.
AB  - OBJECTIVE: The aim of this study was to evaluate current prescribing patterns of
      outpatient child psychiatrists in central New York. METHODS: Data were drawn from
      all active files of 1- to 18-year-olds (n = 1292) at eight outpatient treatment
      locations in central New York on one day in 2002. Age, race, gender, diagnoses,
      current medications, and doses were recorded. Data was tabulated and analyzed to
      discern prescribing frequencies and patterns. RESULTS: 74% (956 of 1292) of all
      patients received psychotropic medication, and 50% of these patients (478 of 956)
      received two or more medications. The most commonly prescribed medications were
      stimulants, antidepressants, antipsychotics, alpha-agonists, and "mood
      stabilizer" anticonvulsants. The most frequent diagnoses were attention
      deficit/hyperactivity disorder, other disruptive behavior disorders, anxiety
      disorders, and depressive disorders. Of those youths who received an
      antipsychotic medication, 77% did not have a diagnosis of a psychotic disorder.
      CONCLUSIONS: Psychotropic prescribing frequency in outpatient child psychiatry
      continues to increase, with a substantial majority of youth in psychiatric
      treatment receiving medication. Stimulants, antidepressants, and antipsychotics
      have led the way, as in prior studies. Co-prescribing represents a substantial,
      and growing, proportion of prescribing practice. Antipsychotics are frequently
      prescribed for nonpsychotic conditions.

PMID- 15741787
TI  - Treatment with stimulants among youths in a large California health plan.
AB  - OBJECTIVE: The aim of this study was to examine the use of stimulants among
      youths in a large and diverse health plan in California from 1996-2000. METHODS:
      Computerized pharmacy, outpatient visit, and membership files were used to
      conduct a population-based analysis of stimulant use among over 500,000 enrollees
      aged 2-18 years. Annual prevalence rates of stimulant use were estimated by
      calendar year, age, gender, and geographic area. RESULTS: The annual percentage
      of continuously enrolled 2- through 18-year-olds receiving at least one
      prescription for a stimulant rose from 1.86% (95% confidence interval (CI) 1.82
      1.90) in 1996 to 1.93% (95% CI, 1.90-1.96) in 2000. An increase was observed only
      among girls 8 years of age or older and among boys 12 years or older. Use of
      methylphenidate decreased, whereas use of extended-release amphetamine products
      increased. Stimulant use was lower and use of other psychotropic drugs was higher
      among children with visits for attention-deficit/hyperactivity disorder (ADHD)
      and a coexisting psychiatric disorder than among those seen for ADHD alone. Of
      the 11,698 children receiving at least one stimulant in 2000, 24% of these
      children received a single prescription. Approximately 55% of stimulant
      prescriptions were written by physicians in pediatrics and 45% by physicians in
      psychiatry. CONCLUSIONS: The prevalence of treatment with stimulants was lower
      than what generally has been reported in other parts of the United States; it
      increased by approximately 4% between 1996 and 2000, and was frequently short
      term or intermittent.

PMID- 15741788
TI  - Multiple psychotropic medication use for youths: a two-state comparison.
AB  - OBJECTIVE: The aim of this study was to compare multiple psychotropic use among
      youths enrolled in two U.S. mid-Atlantic state Medicaid and state Children's
      Health Insurance Programs (SCHIP). METHODS: Administrative data were used to
      examine multiple psychotropic use among youths less than 20 years of age and who
      were continuously enrolled in Medicaid or SCHIP programs in two states during
      1999. Multiple psychotropic use referred to multiclass combinations and was
      defined by the number of months of multiple use. Main outcome measures were the
      prevalence of multiple psychotropic use and months of multiple use. Demographic
      and clinical characteristics, mental health visits, and common combinations were
      examined according to months of multiple use. RESULTS: Among continuously
      enrolled youths, 21%-22% had at least one mental health-related visit, 8%-10%
      received a psychotropic medication, and 2%-3% received multiple psychotropic
      medications. Nearly one third (28%-30%) of youths with any psychotropic use
      received multiple medications, of which almost half was for 5-12 months.
      Multiclass use was more common in male, white, aged 10-14, disabled, and foster
      care youths. Stimulants with antidepressants, antipsychotics, or alpha-agonists
      were the most common combinations. CONCLUSIONS: Multiple use occurred in nearly
      one third of youths with any psychotropic treatment. Additional research is
      needed to investigate switching patterns and the effectiveness of combined
      pharmacotherapy.

PMID- 15741789
TI  - Use and persistence of pharmacotherapy for elementary school students with
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: The aim of this study was to describe rates of attention
      deficit/hyperactivity disorder (ADHD) medication treatment and relevant school
      services use during a 2-year period, and to examine independent predictors of
      these interventions. METHOD: Parent and child interviews (n = 266) and follow-up
      12-month telephone surveys (n = 220) were conducted among a high-risk sample,
      selected from a districtwide, stratified, random sample of elementary-school
      students screened for ADHD risk. Medication treatment status and school services
      use were assessed from multiple sources, and their predictors were identified by
      logistic regression modeling, adjusting for sociodemographic and parental
      characteristics, as well as clinical-need variables. RESULTS: Approximately one
      third (35%) of the children received ADHD medications during a 2-year period, and
      of those treated at Time 2, approximately one third (36%) were no longer on
      medications at Time 3. Boys were more than twice as likely to receive ADHD
      medication as girls. Approximately one quarter (28%) of the children accessed
      school services and continued their use over 2 years. African-American youths
      were more likely to receive school services than were Caucasian children.
      CONCLUSIONS: In this elementary school-district high-risk sample, care for ADHD
      was remarkable for underuse and attrition of medication treatment, as well as
      poor linkage to relevant school services. Interventions to improve ADHD care
      should include supports to access and sustain medication treatment, as well as
      link with school services, especially for girls.

PMID- 15741790
TI  - Race/ethnicity and insurance status as factors associated with ADHD treatment
      patterns.
AB  - Using data from the 1997-2000 Medical Expenditure Panel Survey (MEPS),
      disparities in different stages of attention-deficit/hyperactivity disorder
      (ADHD) health care were investigated, from initial detection to follow-up
      physician visits and psychotherapy appointments. Differences in ADHD diagnoses,
      stimulant usage, and health-care visits were examined by age, race/ethnicity,
      region, and type of insurance. Major significant findings were: (1) children
      without insurance had lower levels of care in all stages relative to children
      with insurance, (2) Hispanic-American and African-American children were less
      likely to be diagnosed with ADHD by parent report than were white American
      children, and (3) African-American youths with ADHD were less likely to initiate
      stimulant medication relative to white American children. Implications for
      expanding childhood health insurance coverage, and for future work on minority
      mental health care in regard to ADHD, are discussed.

PMID- 15741791
TI  - Psychotropic medication use in a national probability sample of children in the
      child welfare system.
AB  - OBJECTIVES: The aim of this study was to estimate the point prevalence of
      psychotropic medication use, and to describe relationships between child-level
      characteristics, provider type, and medication use among children in the child
      welfare system. METHODS: The National Survey of Child and Adolescent Well-Being
      is the first nationally representative study of children coming into contact with
      the child welfare system. We used data from its baseline and 12-month follow-up
      waves, and conducted weighted bivariate analyses on a sample of 3114 children and
      adolescents, 87% of whom were residing in-home. RESULTS: Overall, 13.5% of
      children in child welfare were taking psychotropic medications in 2001-2002.
      Older age, male gender, Caucasian race/ethnicity, history of physical abuse,
      public insurance, and borderline scores on the internalizing and externalizing
      subscales of the Child Behavior Checklist were associated with higher proportions
      of medication use. African-American and Latino ethnicities, and a history of
      neglect, were associated with lower proportions of medication use. CONCLUSIONS:
      These national estimates suggest that children in child welfare settings are
      receiving psychotropic medications at a rate between 2 and 3 times that of
      children treated in the community. This suggests a need to further understand the
      prescribing of psychotropic medications for child welfare children.

PMID- 15741792
TI  - Psychotropic medication use among Kansas Medicaid youths with disabilities.
AB  - Knowledge of current patterns of psychotropic medication use by disabled youths
      is an important starting point for targeting future efforts to improve
      prescribing practices. This study provides a retrospective, descriptive analysis
      of the prevalence and patterns of psychotropic medication among 1022 Kansas
      Medicaid youths in 2001 who were enrolled with either Supplemental Security
      Income (SSI) or Medically Needy benefits and who were having clearly defined
      mental and neurological disabilities. Rates of psychotropic medication use were
      generally higher for the Medically Needy than for the SSI youths: Central nervous
      system (CNS) stimulants (24.6% versus 20.0%), antidepressants (30.9% versus
      13.7%), anticonvulsants (22.0% versus 13.9%), and antipsychotics (23.3% versus
      11.5%). Use of the four major drug classes varied among children with attention
      deficit/hyperactivity disorder (ADHD) and disruptive disorders, pervasive
      developmental disabilities, mental retardation (MR) and learning disabilities,
      mood and anxiety disorders, and adjustment disorders. Future work should explore
      the appropriateness and effectiveness of these medications within specifically
      targeted subgroups.

PMID- 15741793
TI  - Medication patterns in patients with autism: temporal, regional, and demographic
      influences.
AB  - To date, there have been relatively few surveys of psychotropic medicine use in
      individuals with autism. Data were analyzed from three statewide surveys that
      employed the same questionnaire and survey methodology. The first was done in the
      Autism Society of North Carolina in 1992-1993 (NC-1, n = 838; Aman et al. 1995);
      the second was done in the Autism Society of Ohio in 1999 (Ohio, n = 417; Aman et
      al. 2003), and the third was done again in the Autism Society of North Carolina
      in 2001 (NC-2, n = 1538; Langworthy-Lam et al. 2002). Response rates ranged from
      48%-56%. Longitudinal trends were examined by comparing the NC-1 and NC-2 data,
      and regional effects were assessed by comparing the NC-2 and Ohio data. There was
      a very large increase in antidepressant utilization from 1993 to 2001, with
      significant increases also occurring for antipsychotics, psychostimulants, and
      alpha-agonists and beta-blockers. Among youths with autism, the use of any
      psychotropic increased from 30.5% in NC-1 to 45.2% in NC-2. Psychotropic
      medication patterns were remarkably consistent across North Carolina and Ohio,
      except that significantly more autism supplements were used in Ohio. We also
      examined subject and demographic variables across studies and found several
      robust correlates of psychotropic medication use. Greater age and handicap, and
      more restrictive placements, were associated with the use of several drug
      classes. Knowledge of these patterns may help families and medical planners
      anticipate future needs.

PMID- 15741795
TI  - The significance of published polymorphisms in 14 cases of mild factor VII
      deficiency.
AB  - Factor VII (FVII) plays a critical role in the initiation of blood coagulation,
      and patients with dysfunctional or reduced levels of this protein are susceptible
      to mucosal bleeding. There is poor correlation between the clinical presentation
      and the phenotypic data; and in cases of a mild bleeding tendency, mild to
      moderate reductions in both FVII antigen and activity may be overlooked. The
      prevalence of FVII deficiency may therefore be underestimated. Polymorphic
      differences throughout the FVII gene are associated with variations in plasma
      FVII antigen and activity levels. This study highlights the significance of mild
      FVII deficiency, and examines the importance of seven previously published
      polymorphisms in such patients.

PMID- 15741796
TI  - Interplay of platelet polymorphisms, risk factors, and von [corrected] Willebrand
      factor [corrected] in determining collagen-adenosine diphosphate PFA-100 results
      in patients with coronary artery disease.
AB  - Platelets play a pivotal role in thrombus formation in patients with coronary
      artery disease (CAD), since the high shear generated in the presence of severe
      coronary stenoses can increase platelet reactivity (PR) and trigger
      thrombogenesis. Several reports have suggested a functional effect of human
      platelet antigen (HPA)-1 and HPA-2 gene polymorphisms on PR. However, the true
      determinants of high-shear PR in CAD patients taking their usual medications are
      still incompletely understood. In 104 patients with stable CAD we analyzed the
      possible clinical, biochemical and genetic factors affecting high-shear PR,
      measured by the ex vivo platelet function analyzer (PFA-100) collagen-adenosine
      diphosphate method. In univariate analysis, a lower PR was associated with
      decreased plasma von Willebrand factor-ristocetin cofactor activity, increased
      blood levels of triglycerides, female sex, use of thienopyridines, lower platelet
      count, and HPA-1b carriership. All variables, except HPA-1b, remained associated
      with lower PR in multivariate analysis. However, the introduction in the model of
      the HPA-1 and HPA-2 genotypes as interaction terms led to a significant
      improvement in the prediction of PR, although the quantitative effect was small
      (about 3% improvement, P=0.046).Thus, in CAD patients, there seems to be only a
      mild effect of the platelet glycoprotein HPA-1 and HPA-2 polymorphisms on
      collagen-adenosine diphosphate-stimulated PR after the effect of well-established
      clinical and biochemical determinants are considered.

PMID- 15741797
TI  - CD40-ligand-dependent induction of COX-2 gene expression in endothelial cells by
      activated platelets: inhibitory effects of atorvastatin.
AB  - Increasing evidence shows the importance of platelet-endothelial cell
      interactions in the progression of atherosclerosis. Platelets contribute to
      coronary events both as major components of thrombi and as a triggering factor in
      inflammation that leads to plaque vulnerability. Recent data suggest that
      statins, besides their lipid-lowering properties, exert pleiotropic effects that
      may be beneficial in atherosclerosis. Whether activated platelets influence
      cyclooxygenase-2 (COX-2) expression in human umbilical vein endothelial cells
      (HUVEC), the effect of atorvastatin, and possible mechanisms were investigated.
      COX-2 gene expression in HUVEC was studied using real-time polymerase chain
      reaction. CD40 ligand surface expression of platelets was tested by fluorescence
      activated cell sorting analyses. Activated platelets significantly up-regulated
      COX-2 gene expression in HUVEC. Co-incubation of platelets with atorvastatin was
      shown to reverse this up-regulation via reduction of CD40 ligand surface
      expression on platelets. Data suggest that atorvastatin influences CD40-CD40
      ligand-dependent platelet-endothelial interaction and that this influence affects
      platelet-induced COX-2 expression in HUVEC.

PMID- 15741798
TI  - The binding of fibrin sealant to collagen is influenced by the method of
      purification and the cross-linked fibrinogen-fibronectin (heteronectin) content
      of the 'fibrinogen' component.
AB  - Two fibrinogen preparations, each an intermediate in the manufacture of the
      'fibrinogen' component of a commercial human tissue sealant, were made from a
      common cryoprecipitate source. The first preparation, prepared according to the
      process described by Schwartz et al. had a higher ratio of clottable to total
      protein than the second preparation, prepared according to that by Martinowitz
      and Bal but a much lower ratio of fibronectin to fibrinogen. After clotting with
      thrombin and solubilization and reduction of the clots, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed a much higher content of high
      molecular weight polymers of fibrin(ogen) in the second preparation than in the
      first. The second preparation bound to collagen more strongly than did
      cryoprecipitate and much more strongly than did the first one. Experiments with
      highly purified proteins showed that fibronectin was essential in promoting
      progressive binding of fibrinogen to collagen under the action of activated
      factor XIII (transglutaminase). It was concluded that, because of their method of
      purification from cryoprecipitate, preparations of fibrinogen differ in their
      content of fibronectin and heteronectin. The binding of these proteins to
      collagen may improve the adhesion of tissue sealant clots to the extracellular
      matrix.

PMID- 15741799
TI  - Hemostatic factors as predictors of stroke and cardiovascular diseases: the
      FINRISK '92 Hemostasis Study.
AB  - We carried out a prospective cohort study to determine whether the plasma levels
      of fibrinogen, plasminogen, factor VII and lipoprotein (a) are predictors of
      ischemic stroke and all cardiovascular disease (CVD) events. The FINRISK '92
      Hemostasis Study included a random sample of 2372 participants, who were followed
      up from winter 1992 to 31 December 2001. During the follow-up, 75 ischemic stroke
      and 145 coronary events occurred. Of these, 169 were observed among participants
      free of known CVD at baseline. In this group, fibrinogen and plasminogen were
      positively associated with the risk of a CVD event with hazard ratios of 1.22
      [95% confidence interval (CI), 1.05-1.41] and 1.22 (95% CI, 1.03-1.44),
      respectively, after adjusting for age, sex and conventional risk factors. Factor
      VII:C was associated with risk of a future CVD event only among persons with
      positive history of CVD at baseline (hazard ratio, 1.32; 95% CI, 1.00-1.73).
      Factor VII antigen was not associated with CVD risk. None of the measured
      hemostatic factors was a predictor of ischemic stroke events, with the possible
      exception of lipoprotein (a), which had a borderline significant association
      (hazard ratio, 1.25; 95% CI, 0.99-1.58). In conclusion, the present study
      supports the observations that fibrinogen and plasminogen are significant
      predictors of CVD events, independently of conventional risk factors.

PMID- 15741800
TI  - Determination of prothombinase activation after adding human purified prothrombin
      to human clot: comparison of hirudin, an activated factor II inhibitor, with
      DX9065a, an activated factor X inhibitor, on clot-associated thrombin and on
      prothrombin activation.
AB  - Clot-associated prothrombinase and thrombin activities may contribute to thrombus
      extension after thrombolytic and anticoagulant treatment. We studied prothrombin
      activation after adding human purified prothrombin to human clot. By using two
      different drugs with an exclusive direct anti-activated factor X activity
      (DX9065a) or anti-activated factor II activity (r-hirudin), we tried to determine
      whether clot-bound thrombin and prothrombinase could be inhibited in our
      experimental system when human purified prothrombin was added. Standard clots
      were prepared from platelet-poor human plasma after addition of calcium. We
      measured clot-bound thrombin or free thrombin using a direct simple chromogenic
      assay. In parallel, prothrombin fragment 1+2 measurement was used to monitor
      prothrombin activation. For this, two protocols were used. We introduced the
      direct inhibitors before starting the activation process (protocol A) or at the
      time of the activation process (protocol B). We found a direct correlation
      between thrombin generation and prothrombin fragment 1+2 with an increase of
      thrombin activity on clots and in the incubation mixtures when clots were
      incubated in human purified pothrombin alone. Two protocols were used: in the
      first, clots were pre-incubated in presence of drugs before adding prothrombin;
      and in the second, clots were incubated in the presence of prothrombin and drugs.
      Prothrombin activation was not inhibited when clots were incubated with r-hirudin
      and consequently thrombin generation still occurred. However, added r-hirudin
      blocks thrombin activity on the clots and in the incubation mixture, but does not
      prevent prothrombin activation, as shown by the increase of prothrombin fragment
      1+2. In contrast, DX9065a did not suppress clot-bound thrombin. However, DX9065a
      blocks prothrombin activation whichever protocol was used. The results show that
      hirudin is a poor inhibitor of thrombin generation in contrast to DX9065a. On the
      other hand, DX9065a cannot inhibit thrombin bound to clot in contrast to hirudin.

PMID- 15741802
TI  - Stroke induced by splenectomy in hemoglobin Madrid: autopsy clues to the
      underlying mechanism.
AB  - Thrombo-embolic events, which can be increased after splenectomy in hemoglobin
      disorders, can cause potentially lethal complications. Although venous thrombosis
      has been reported, arterial strokes are rarely reported. A case of stroke in a 52
      year-old patient with a previously performed splenectomy for known hemoglobin
      Madrid, an extremely unstable hemoglobinopathy, led us to investigate the
      possible causal role of splenectomy. The patient had no history of hypertension,
      diabetes mellitus, smoking, or other vascular risk factors--but upon autopsy,
      thrombotic angiopathy was observed in multiple organs, including the lung, liver,
      kidney, coronary artery and brain. Bone marrow hyperplasia was also observed. A
      thrombotic middle cerebral artery territory infarction appears to have been
      caused by chronic recurrent thrombosis, which may have been a result of the
      splenectomy for unstable hemoglobinopathy. This case supports that splenectomy be
      strongly considered as an uncommon risk factor for stroke.

PMID- 15741801
TI  - Protein S type III deficiency is no risk factor for venous and arterial
      thromboembolism in 168 thrombophilic families: a retrospective study.
AB  - Free protein S rather than total protein S levels are currently measured to
      detect inherited protein S deficiency. Because type III (free protein S)
      deficiency is still not established as risk factor for thrombosis, we assessed
      the absolute risk of venous and arterial thromboembolism in a family cohort
      study. Annual incidences in first-degree relatives with and without protein S
      deficiency type III were compared. Probands had experienced thrombosis and had
      either the prothrombin G20210A mutation, increased factor VIII:C levels or
      hyperhomocysteinemia. Relatives were tested for these thrombophilic disorders and
      factor V Leiden. Levels of antithrombin, protein C, total and free protein S, and
      factor XI:C were additionally measured. Of 500 relatives enrolled, 105 were
      excluded from analysis because they could not be classified, due to acquired
      conditions. Protein S deficiency type III was demonstrated in 60/395 remaining
      relatives (15%). Other thrombophilic defects were equally distributed among
      deficient and non-deficient relatives. Annual incidences of venous
      thromboembolism were 0.28 per 100 person-years [95% confidence interval (CI),
      0.09-0.66] in deficient relatives versus 0.20 per 100 person-years (95% CI, 0.12
      0.30) in non-deficient relatives [hazard ratio, 1.4 (95% CI, 0.4-4.0)]. For
      arterial thromboembolism these values were 0.16 per 100 person-years (95% CI,
      0.03-0.46) versus 0.10 per 100 person-years (95% CI, 0.05-0.19) [hazard ratio,
      1.5 (95% CI, 0.3-6.0)]. These results suggest that protein S deficiency type III
      is not associated with an increased risk of either venous or arterial
      thromboembolism.

PMID- 15741803
TI  - Recombinant activated factor VII for severe gastrointestinal bleeding after
      chemotherapy in an infant with acute megakaryoblastic leukemia.
AB  - Recombinant activated factor VII (rFVIIa) is a major alternative for management
      of hemophiliac patients with inhibitors. Additionally, it has been used off-label
      for the treatment of massive life-threatening hemorrhage associated with various
      bleeding situations. Herein, we describe a 16-month-old boy with acute
      megakaryoblastic leukemia and severe intractable gastrointestinal bleeding
      controlled by rFVIIa. rFVIIa should be considered as a novel treatment
      alternative in severe bleeding conditions including leukemias that may have
      hemostatic defects and platelet dysfunction.

PMID- 15741804
TI  - Characterization of molecular defect of 13387-9delG mutated antithrombin in
      inherited type I antithrombin deficiency.
AB  - As a major physiological inhibitor of thrombin and other coagulation proteases,
      antithrombin (AT) plays an important role in the maintenance of normal hemostasis
      and its deficiency is associated with a predisposition for familial venous
      thromboembolic disease. Recently, we found a novel mutation (13387-9delG) in the
      antithrombin gene that is associated with type I AT deficiency. To examine the
      molecular pathologic mechanism of this mutation causing type I AT deficiency, the
      wild-type and the mutant AT constructs were expressed in COS-7 cells or Chinese
      Hamster Ovary cells. No AT antigen could be detected by enzyme-linked
      immunosorbent assay in the conditioned media of cells expressing the mutant
      protein, and the AT antigen level was reduced in cell lysates. The mutant AT
      expressing cells did not have less intracellular mRNA levels than the wild-type
      transfectants as estimated by quantitative reverse transcriptase-polymerase chain
      reaction. Metabolic and pulse-chase experiments showed the newly synthesized wild
      type AT protein was gradually secreted into the media, whereas no labeled mutant
      AT protein was detected in the media and the total amount of radioactivity was
      significantly reduced in the cells during the chase periods. By
      immunofluorescence analysis, the staining of the mutant AT was weaker than that
      of the wild type, and was predominantly diffuse without perinuclear enhancement.
      These results indicate that the 13387-9delG mutation, which disrupts the
      disulfide bridge Cys247-Cys430, impairs the secretion and stability of the
      truncated AT protein associated with intracellular degradation.

PMID- 15741805
TI  - Usefulness of lyophilized calibration plasmas for International Normalized Ratio
      determination with the bovine combined thromboplastin (Thrombotest): results of a
      collaborative study.
AB  - The logical solution to account for the influence of coagulometers on the
      International Sensitivity Index (ISI) is local calibration with freeze-dried
      plasmas. However, because of their unpredictable behavior these plasmas must be
      validated before large-scale implementation. We report on a collaborative
      exercise designed to evaluate the suitability of a set of such plasmas used with
      Thrombotest in combination with a coagulometer provided by the manufacturer to be
      used with that reagent. This was a two-step study. First, one lot of reagent was
      calibrated against the international standard OBT/79 in two expert laboratories.
      The calibrated lot was then used as an intermediate standard to calibrate two
      additional lots of the same reagent in four field laboratories where the ISI was
      determined for both plasma and native blood. The International Normalized Ratio
      (INR) for the patient plasmas tested in each laboratory were calculated using two
      algorithms: the World Health Organization-recommended ISI mode (gold standard),
      and the simplified calibration plasma mode. In the latter, the INR was derived
      from the local calibration curve constructed by plotting the certified INR versus
      local coagulation times obtained with calibration plasmas. The between-algorithm
      INR differences indicate that this set of calibration plasmas may be employed for
      local INR calibration of the investigated reagent/instrument combination,
      especially when plasma is used for INR determination where the average INR
      (range) difference is 5% (3-13%) or 2% (3-8%) according to whether the INRs to
      calibration plasmas were assigned by the manufacturer or by the two expert
      laboratories. A slight but measurable difference of the INR may be predicted [9%
      (6-20%) or 6% (8-15%)] if this set of calibration plasmas is used for local
      calibration when native blood is employed for INR determination. Whether this
      bias is of practical significance is to be determined.

PMID- 15741807
TI  - Trabeculectomy with internal tube shunt: a novel glaucoma surgery.
AB  - PURPOSE: To describe a pilot study that evaluates the efficacy and mechanism of
      action of a new glaucoma operation, trabeculectomy with internal tube shunt.
      METHODS: Twenty-three patients underwent the new operation in one eye for open
      angle glaucoma. Under a scleral flap, a deep sclerectomy was performed, resulting
      in an intrascleral lake. Laterally, on both sides, a small silicone tube was
      placed between the intrascleral lake and the suprachoroidal space. A
      trabeculectomy stoma and a peripheral iridectomy permitted easy access of aqueous
      to the tube. Postoperative and preoperative results were analyzed and also
      compared with results of 45 eyes that underwent a conventional trabeculectomy.
      RESULTS: After a mean follow-up time of 324 days, the mean postoperative IOP was
      13.8 mm Hg compared with a preoperative value of 25.4 mm Hg. The mean number of
      postoperative medications was only 1.1 compared with a preoperative value of 3.0.
      No significant change in outflow facility was seen. The bleb size was very small.
      In comparison, in conventional trabeculectomy eyes, the outflow facility and bleb
      size were significantly larger. CONCLUSION: Trabeculectomy with internal tube
      shunt is very effective in lowering IOP. It is postulated to work, to a large
      extent, by allowing access of the aqueous humor to the suprachoroidal space where
      the protein colloid osmotic pressure of uveal blood causes its absorption. This
      new procedure offers many advantages over other filter procedures and tube
      shunts.

PMID- 15741808
TI  - Implantation of a miniature glaucoma device under a scleral flap.
AB  - PURPOSE: To test the safety and efficacy of the Ex-PRESS miniature glaucoma
      device when it is implanted under a scleral flap instead of under the conjunctiva
      as it was originally suggested. PATIENTS AND METHODS: Between November 2000 and
      February 2003, the Ex-PRESS implant was inserted in 24 eyes of 23 patients with
      severe open angle glaucoma. Sixteen eyes of the 24 (66%) had had previous failed
      filtering surgery. The remaining 8 eyes (33%) were high risk for failures cases.
      A 5 x 5 mm limbal-based, 50% depth, scleral flap was raised into clear cornea.
      The Ex-PRESS implant was inserted into the anterior chamber under the scleral
      flap at the limbus. The scleral flap was securely sutured back, as is done in
      trabeculectomy operations. RESULTS: The intraocular pressure was significantly
      reduced from 27.2 +/- 7.1 mm Hg pre-operatively to 14.5 +/- 5.0 mm Hg at 12
      months (n = 21) and 14.2 +/- 4.2 mm Hg at 24 months (n = 8). Postoperatively,
      only two patients needed anti-glaucoma medications to keep the IOP below 21 mm
      Hg. CONCLUSIONS: The Ex-PRESS device was found to be safe and effective with few
      complications when it is implanted under a scleral flap even in the high-risk
      patients studied.

PMID- 15741809
TI  - Surgical drainage of choroidal effusions following glaucoma surgery.
AB  - PURPOSE: To determine the efficacy and safety of surgical drainage of choroidal
      effusions that occurs following glaucoma surgical procedures. PATIENTS AND
      METHODS: Ninety-four choroidal drainage procedures performed at a single
      institution from 1986 to 2001 were reviewed retrospectively. Sixty-three eyes of
      63 persons who underwent one or more drainage procedures for choroidal effusions
      that developed following glaucoma surgical procedures were identified. Eyes
      diagnosed with suprachoroidal hemorrhage prior to intervention were excluded. The
      cases were evaluated for resolution of choroidal detachment, post-drainage
      complications, visual acuity, and intraocular pressure before and after drainage.
      RESULTS: Indications for choroidal drainage included flat anterior chamber (25
      eyes), decreased vision (22 eyes), and persistent choroidal detachment (16 eyes).
      Complete resolution of choroidal effusions was achieved in 37 (59%) eyes by 1
      month, 51 (81%) eyes by 2 months, and in 57 (90%) eyes by 4 months following the
      initial drainage procedure. Overall success rate per procedure at 12 months was
      77% (60/78). Compared with pre-drainage, intraocular pressure was higher at 6 and
      12 months post-drainage (P < 0.0001) and visual acuity was better at 6 and 12
      months post-drainage (logMAR, P < 0.0001). Twenty-seven (77%) of 35 phakic eyes
      developed cataracts during the 12 months post-drainage. CONCLUSIONS: Choroidal
      effusions that develop after glaucoma surgery can usually be drained with minimal
      complications. Surgical drainage is associated with improved vision and
      resolution of hypotony. Cataracts may progress following choroidal drainage but
      this may be due to the pre-drainage hypotony conditions.

PMID- 15741811
TI  - Diode laser transscleral cyclophotocoagulation as primary surgical treatment for
      medically uncontrolled chronic angle closure glaucoma: long-term clinical
      outcomes.
AB  - PURPOSE: To evaluate the long-term efficacy and safety of diode laser
      transscleral cyclophotocoagulation as primary surgical treatment of medically
      uncontrolled chronic angle closure glaucoma. PATIENTS AND METHODS: Thirteen eyes
      of 13 Chinese patients with medically uncontrolled chronic angle closure glaucoma
      were treated with diode laser transscleral cyclophotocoagulation between February
      2000 and May 2001, and followed up for over 18 months. Post-treatment anti
      glaucoma medications were adjusted according to intraocular pressure. If
      intraocular pressure remained above 21 mm Hg despite medications for more than 4
      weeks after cyclophotocoagulation, the procedure was repeated. RESULTS: Mean
      follow-up +/- SD was 26.5 +/- 4.2 months. Two eyes required repeat
      cyclophotocoagulation at 6 weeks. Rate of relative success, defined as
      maintaining an intraocular pressure of 21 mm Hg or below with or without
      medications, was 92.3% (12 of 13 eyes). Rate of absolute success, defined as
      maintaining an intraocular pressure of 21 mm Hg or below without medications, was
      0% (0 of 13 eyes). Mean +/- SD intraocular pressure was reduced from 36.4 +/-
      12.6 mm Hg pre-operatively, to 18.7 +/- 12.2 mm Hg at final follow-up (P = 0.003,
      paired t test). The mean +/- SD number of intraocular pressure-lowering eye drops
      was reduced from 2.0 +/- 0.8 pre-operatively, to the lowest point of 0.5 +/- 0.8
      at 12 months, and then gradually increased to 2.1 +/- 0.9 at final follow-up. The
      visual acuity improved after treatment in 2 of 13 eyes (15.4%), remained
      unchanged in 6 of 13 eyes (46.2%) and deteriorated in 5 of 13 eyes (38.5%). No
      major complications were encountered. CONCLUSION: Diode laser
      cyclophotocoagulation appeared to be an effective and safe primary surgical
      treatment of medically uncontrolled chronic angle closure glaucoma, with
      intraocular pressure-lowering effect persisting for up to two years.

PMID- 15741810
TI  - The effect of laser iridotomy on the anterior segment anatomy of patients with
      plateau iris configuration.
AB  - PURPOSE: To determine if laser iridotomy altered the anterior segment anatomy of
      patients with plateau iris configuration. METHODS: Twenty eyes of 9 female and 1
      male patients were imaged using an ultrasound biomicroscope within 19 weeks
      before and 52 weeks after laser iridotomy. Measurements obtained included the
      anterior chamber depth (ACD), trabecular-ciliary process distance (TCPD), iris
      thickness (IT), angle opening distance at 500 micrometers (AOD), iridozonular
      distance (IZD), and trabecular-iris angle (TIA). Comparisons of the pre- and post
      iridotomy measurements were made using a two-tailed paired t test. RESULTS:
      Laser iridotomy elicited no statistically significant change in ACD, TCPD, IT,
      AOD, or TIA. However, IZD was decreased (P < 0.05) in both eyes after laser
      iridotomy. Configuration of the irides was flat before and after laser
      iridotomies. CONCLUSION: This study suggests that laser iridotomy did not alter
      anterior segment anatomy, probably because of the fixed anterior insertion of the
      iris and ciliary body in plateau iris configuration. The decrease in IZD distance
      may be the result of a small posterior movement of the iris due to a reduction in
      relative pupillary block, secondary to laser iridotomy. The small reduction in
      relative papillary block in plateau iris configuration does not alter the width
      of the anterior chamber angle as measured by AOD and TIA.

PMID- 15741812
TI  - Level of disagreement between Proview phosphene tonometer and Goldmann
      applanation tonometer intraocular pressure readings.
AB  - PURPOSE: To evaluate the agreement of intraocular pressure (IOP) readings
      obtained with the Proview phosphene tonometer and those obtained by Goldmann
      applanation tonometry as well as the effect of regular use of the Proview on
      patients' anxiety about their glaucoma. METHODS: One hundred thirty-five
      consecutive patients with glaucoma, 35 designated as controls, were enrolled in a
      10-month randomized prospective clinical trial. The study patients but not the
      controls used the Proview outside the office. At office visits IOP was measured
      by an ophthalmologist with the Goldmann applanation tonometer (GAT) as well as by
      examiners and patients using the Proview. Patients in the treatment group (n =
      100) were asked to measure and record their IOP at home as well. Using ANOVA, we
      examined the relationship between demographic variables and the level of
      agreement between the Proview readings and those measured by GAT at the final
      office visit. All participants also were asked to complete a questionnaire
      regarding their anxiety about their IOP at the baseline and final office visits.
      The primary outcome measure was the level of agreement of the Proview
      measurements with those obtained by GAT. Secondary outcome measures included
      patients' anxiety about their glaucoma. RESULTS: The absolute mean difference
      between GAT and Proview readings at the final visit was 3.5 +/- 2.9 mm Hg
      (median, 2.8 mm Hg). The treatment group reported significantly less anxiety
      about their glaucoma after 4 to 6 weeks of using the Proview (P = .024).
      CONCLUSIONS: There was considerable discrepancy between Proview and GAT readings.
      However, regular use of the Proview tonometer significantly reduced patients'
      anxiety about their glaucoma.

PMID- 15741813
TI  - Influence of pupillary diameter, ciliary muscle tone, and ambient light on nerve
      fiber layer measurements with scanning laser polarimetry.
AB  - PURPOSE: To evaluate the influence of the pupillary diameter, ciliary muscle
      tone, and room light on nerve fiber layer measurements with the scanning laser
      polarimeter (GDx). METHODS: One randomly selected eye of ten normal volunteers
      was examined with the GDx in a two-day protocol under eight testing conditions
      (pilocarpine 1%, phenylephrine 10%, tropicamide 1%, or no drops with room lights
      on or off). The twelve parameters, obtained by the GDx, were compared under the
      eight testing conditions, using two way ANOVA for repeated measurements and Tukey
      HSD post hoc test. RESULTS: Ten of the twelve parameters were statistically
      significantly different (P < 0.05) when measured under the three medication or no
      medication conditions, controlling for the ambient light status. There were no
      significant differences when measured with the light on or off, controlling for
      use of drops. CONCLUSIONS: Nerve fiber layer measurements with the GDx were
      influenced by drugs affecting pupillary diameter, but not by the status of room
      light or ciliary muscle tone.

PMID- 15741814
TI  - Predictive value of frequency doubling technology perimetry for detecting
      glaucoma in a developing country.
AB  - PURPOSE: To determine the feasibility and diagnostic precision of Frequency
      Doubling Technology (FDT) perimetry as a method to detect glaucoma in rural
      villages of a developing country. DESIGN: Cross-sectional study. METHODS: Testing
      included FDT perimetry (C-20-5 screening protocol), tonometry, anterior segment
      biomicroscopy, and dilated ophthalmoscopy in 296 rural, non-English speaking
      residents of Southern India over 35 years old. Participants repeated the FDT if
      they had a location with reduced sensitivity or an unreliable result. We defined
      an abnormal FDT as one location of reduced sensitivity present on both the
      initial and repeat examination. We determined the diagnostic precision of FDT
      separately for a glaucomatous optic disc, a cup to disc ratio (C/D) > or = 0.7,
      and a C/D > or = 0.8. RESULTS: Ninety-three percent of subjects were able to
      complete the test satisfactorily. With repeat FDT testing, 37% of eyes with
      abnormal FDT results subsequently converted to normal and 67% of eyes with
      unreliable results subsequently became reliable. The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy for a
      glaucomatous optic disc were 7%, 87%, 13%, 76%, and 69%, respectively; for a C/D
      > or = 0.7, they were 0%, 87%, 0%, 91%, and 81%, respectively; and for a C/D > or
      = 0.8, they were 0%, 87%, 0%, 99%, and 87%, respectively. CONCLUSION: Clinicians
      can use FDT perimetry to rapidly screen for glaucoma in rural villages of a
      developing country. FDT testing had high specificity and negative predictive
      value, but low sensitivity and positive predictive value. The low sensitivity
      suggests that FDT has limited applicability as the sole test for glaucoma
      screening in this population. Repeat testing of FDT results that are unreliable
      or suspected of being abnormal is beneficial for this screening procedure.

PMID- 15741815
TI  - A long-term prospective study of risk factors for glaucomatous visual field loss
      in patients with ocular hypertension.
AB  - PURPOSE: To evaluate the importance of baseline risk factors for development of
      glaucomatous visual field loss in patients with high-risk ocular hypertension.
      METHODS: In the Malmo Ocular Hypertension Study, 90 patients were randomized to
      topical timolol or placebo treatment and observed prospectively for up to 10
      years. Patients with elevated intraocular pressure (IOP) and with open angles and
      normal visual fields, plus at least one extra risk factor, were eligible. Risk
      factors were suspect disc or known disc hemorrhage, positive family history of
      glaucoma, pseudoexfoliation or pigment dispersion syndrome, diabetes, and mean
      IOP on DTC > or = 27 mm Hg. These risk factors and also the mean baseline IOP and
      IOP fluctuation, sex, age, and blood pressure were evaluated as predictors for
      development of reproducible glaucomatous visual field loss. In addition to the
      prospective data, post-study data were retrieved from patients' records extending
      maximum follow-up to 17 years. RESULTS: Thirty-seven patients developed
      glaucomatous visual field loss. Of all factors included in the analysis, disc
      appearance, older age, and higher IOP came out as significant risks. Suspect disc
      appearance increased the risk approximately three times, with a hazard ratio of
      2.90, and CI: 1.34-6.30, the hazard ratio was 1.05 and CI: 1.03-1.09 per year of
      age, while mean baseline IOP increased the risk with 14% per mm Hg (CI: 1.01
      1.28). CONCLUSION: Patients with ocular hypertension were at higher risk for
      developing glaucomatous visual field loss if discs were suspect, if IOP was high,
      and if the patient was older in age.

PMID- 15741816
TI  - Primary congenital glaucoma presenting within the first three months of life in a
      Bedouin population: prognostic factors.
AB  - OBJECTIVES: To analyze the final outcome of surgery in Arab-Bedouin children with
      primary congenital glaucoma (PCG) presenting within the first three months of
      life, and to search for prognostic factors for success. DESIGN: Retrospective
      study of all cases with follow-up of at least 24 months. PATIENTS: Twenty-five
      Arab-Bedouin children (45 eyes) with PCG presenting within the first three months
      of life who underwent surgical procedures at the Soroka University Medical Center
      from January 1988 to December 1998. METHODS: Patient's age, family history, main
      presenting features, data from examinations under anesthesia, including
      intraocular pressure (IOP), horizontal corneal diameter, and cup/disc (c/d)
      ratio, and the type of surgery performed were reviewed. MAIN OUTCOME MEASURES:
      Success of the first operation, defined as final IOP < 21 mm Hg achieved after
      only one surgical procedure without anti-glaucoma medication, and final outcome,
      defined as good when IOP was < 21 mm Hg and > 5 mm Hg at the end of a 24-month
      follow-up period without anti-glaucoma medication, irrespective of the number of
      procedures performed. RESULTS: At presentation mean IOP was 36.2 +/- 8.0 mm Hg,
      corneal diameter was 12.62 +/- 0.98 mm, and c/d ratio was 0.41 +/- 0.16. The mean
      age at first operation was 17 +/- 20 days, and median of 5 days. The mean follow
      up period was 37.4 +/- 25.4 months. The success of the first operation performed
      was not related to the type of operation (P = 0.22), gender (P = 0.47),
      consanguinity (P = 1.0), family history (P = 0.12), clinical presentation (P =
      0.81), or age at first operation (P = 0.38). Eyes with high initial IOP and
      greater c/d ratio were at a significantly higher risk for failure (P = 0.05, P =
      0.04, respectively). A final outcome of IOP under 21 mm Hg and above 5 mm Hg was
      achieved in 39 eyes (86.5%). There was no statistical association between final
      outcome and the type of first surgical procedure performed, gender,
      consanguinity, clinical presentation, and age at first operation. Cases with no
      family history had a significantly better final outcome (P = 0.05). In
      multivariate analysis only initial IOP showed borderline significance as an
      independent risk factor for final outcome (P = 0.06). CONCLUSIONS: Initial high
      IOP and higher c/d ratio were found to be predictive factors for failure of the
      first procedure. Final outcome was significantly better in cases with no family
      history, yet initial IOP was the only independent predictive factor for failure
      at the final outcome in a multivariate model. Findings of this type have not been
      previously reported, and they may constitute an important tool in predicting the
      treatment outcome of very young children with PCG.

PMID- 15741817
TI  - Driving performance of glaucoma patients correlates with peripheral visual field
      loss.
AB  - PURPOSE: To identify clinical vision measures that are associated with the
      driving performance of glaucoma patients who have visual field loss and visual
      acuity better than 20/100 and to compare the driving performance of glaucoma
      patients with the driving performance of a group of age- and sex-equivalent
      individuals without eye disease. PATIENTS: Forty patients with glaucoma and 17
      normally sighted control subjects participated in this study. METHODS: Clinical
      vision data, consisting of visual acuity, letter contrast sensitivity, and visual
      fields, were collected. Driving performance was assessed by (1) an interactive
      driving simulator that measured 7 indices of performance (including number of
      accidents) and (2) the self-reported accident involvement for the past 5 years.
      MAIN OUTCOME MEASURES: Driving simulator performance and real-world, self
      reported accident involvement. RESULTS: The number of accidents as measured on
      the driving simulator in the glaucoma group was significantly correlated with
      three Goldmann visual field measures: combined horizontal extent (rho = -0.47, P
      = 0.01), total horizontal extent (rho = -0.49, P = 0.007), and total peripheral
      extent (rho = -0.55, P = 0.002). There were no statistically significant
      correlations between the driving performance of the glaucoma group and the visual
      acuity or contrast sensitivity measures. When compared with the control group, a
      significantly greater proportion of the glaucoma group reported having at least
      one real-world accident within the past 5 years (Fisher exact test, P = 0.005).
      CONCLUSIONS: Visual field reduced to less than 100 degrees of horizontal extent
      may place patients with peripheral field loss at greater accident risk. A higher
      incidence of real-world and simulator accidents was found for the group with
      glaucoma.

PMID- 15741818
TI  - Preferences for eye drop characteristics among glaucoma specialists: a
      willingness-to-pay analysis.
AB  - PURPOSE: To determine the importance that US glaucoma specialists place on
      attributes of eye drops for lowering intraocular pressure. MATERIALS AND METHODS:
      We performed a cross-sectional survey by conducting a telephone interview with
      113 members of the American Glaucoma Society. We administered a willingness-to
      pay (WTP) instrument asking glaucoma specialists how much they would pay to
      obtain particular characteristics in an eye drop. Demographic data were
      correlated with the WTP responses. We compared the glaucoma specialists'
      responses to those previously obtained from patients. The main outcome measure
      was willingness-to-pay more (in US dollars). RESULTS: Almost all respondents were
      willing to pay extra to reduce the frequency of administration of eye drops from
      3 times a day to once a day, and to avoid blurred vision, drowsiness, or
      inhibition of sexual performance. Only 54 (48%) were willing to pay more to avoid
      iris darkening. The mean amount that respondents were willing to pay (relative to
      US 50 dollars) differed significantly across eye drop characteristics (P <
      0.001). The mean amount that the respondents were willing to pay was highest for
      avoidance of inhibition of sexual performance (US 105 dollars), blurred vision
      (US 92 dollars), and drowsiness (US 92 dollars). When compared with glaucoma and
      glaucoma suspect patients, more ophthalmologists were likely to pay extra for
      desirable eye drop attributes. However, the magnitude of the extra amount was
      similar between ophthalmologists and patients. CONCLUSIONS: Glaucoma specialists
      place differing value on various eye drop characteristics. Although the
      proportion of glaucoma specialists willing to pay more is generally greater than
      the proportion of patients, the preferences of glaucoma specialists and patients
      are alike.

PMID- 15741819
TI  - The effect of combination pharmacotherapy on the prescription trends of glaucoma
      medications.
AB  - PURPOSE: To describe prescription trends within a managed care setting for
      glaucoma medications and to examine the effect of introduction of Cosopt--a fixed
      combination of dorzolamide and timolol. PATIENTS AND METHODS: All prescriptions
      dispensed to any of the 470,350 members of an Israeli health maintenance
      organization were monthly scanned for patients treated for glaucoma, between
      January 2000 and May 2003. The monthly mean number of glaucoma patients was 3899
      +/- 104 (mean +/- SD). All topical glaucoma prescriptions were documented, and
      the monthly prescription rate of each medication was calculated and plotted. The
      monitored glaucoma medications were: beta-adrenergic antagonists, dorzolamide,
      latanoprost, pilocarpine, brimonidine, Cosopt, and others. RESULTS: beta
      adrenergic antagonists were the top prescribing drug (>35% of all glaucoma
      prescriptions). The prescription rates of pilocarpine and beta-adrenergic
      antagonists were in constant decline, while latanoprost and brimonidine increased
      steadily. The introduction of Cosopt changed the prescription trends of
      dorzolamide from increasing to rapidly decreasing, and accelerated the long-term
      decline of beta-adrenergic antagonists. Concomitant with the introduction of
      Cosopt the prescription rate of beta-adrenergic antagonists temporarily
      increased. This was due to a total increase in glaucoma prescriptions. When
      Cosopt was introduced, 37.5% of patients were prescribed Cosopt together with
      beta-adrenergic antagonists, and 16.5% also received dorzolamide. Thereafter the
      co-prescription decreased steadily. CONCLUSIONS: Introduction of a combination
      drug should be accompanied by physicians', pharmacists', and patients' education
      to prevent its inappropriate usage together with its components.

PMID- 15741820
TI  - Latanoprost or brimonidine as treatment for elevated intraocular pressure:
      multicenter trial in the United States.
AB  - PURPOSE: To compare the efficacy and tolerability of latanoprost or brimonidine
      in patients with elevated intraocular pressure (IOP). MATERIALS AND METHODS: This
      prospective, randomized, masked-evaluator, parallel-group, multicenter study in
      the United States included patients with primary open angle glaucoma or ocular
      hypertension. Patients received latanoprost 0.005% once daily (8:00 AM; n = 152)
      or brimonidine tartrate 0.2% twice daily (8:00 AM and 8:00 PM; n = 151). Patients
      underwent evaluation at screening, baseline (randomization), and after 0.5, 3,
      and 6 months of treatment. IOP was measured at 8:00 AM, 10:00 AM, noon, and 4:00
      PM at baseline and the months 3 and 6 visits, and at 8:00 AM only at week 2. The
      main outcome measure was the difference in diurnal IOP change from baseline to
      month 6 between treatment groups. Adverse events were recorded at each visit.
      RESULTS: Baseline mean diurnal IOP levels were similar between groups. At month
      6, the adjusted mean (+/- SEM) diurnal IOP reduction was 5.7 +/- 0.3 mm Hg in the
      latanoprost group and 3.1 +/- 0.3 mm Hg in patients receiving brimonidine (P <
      0.001). The mean difference in diurnal IOP reduction was 2.5 +/- 0.3 mm Hg (95%
      CI: 1.9, 3.2; P < 0.001). Five times more patients receiving brimonidine than
      latanoprost were withdrawn from the study due to adverse events. CONCLUSION:
      Latanoprost instilled once daily is more effective and better tolerated than
      brimonidine administered twice daily for the treatment of patients with glaucoma
      or ocular hypertension. During therapy, the range of daily fluctuation of IOP is
      less for latanoprost compared with brimonidine.

PMID- 15741821
TI  - Intravitreal triamcinolone acetonide and secondary ocular hypertension.

PMID- 15741822
TI  - 2002 survey of the American Glaucoma Society: practice preferences for glaucoma
      surgery and antifibrotic use.
AB  - PURPOSE: To determine the preference of members of the American Glaucoma Society
      for the use of antifibrotic agents (mitomycin C or 5-fluorouracil or both) and
      glaucoma drainage devices in ten clinical settings. MATERIALS AND METHODS:
      Voluntary written survey of the American Glaucoma Society. RESULTS: American
      Glaucoma Society (AGS) members continue to report preference for mitomycin C use
      in ten clinical settings. The percent usage for glaucoma drainage devices has
      increased in poor prognosis scenarios including the following: neovascular
      glaucoma, previous failed trabeculectomy, previous ECCE/ICCE, previous PKP,
      previous scleral buckling surgery, and uveitic glaucoma. However, trabeculectomy
      and MMC continue to be more likely employed for surgical management. CONCLUSION:
      Despite the long-term complications of bleb-related infections, no statistically
      significant shift in preference away from MMC use or reduction in the
      concentration of drug delivery was observed since the 1996 survey.

PMID- 15741823
TI  - Effects of marijuana on aqueous humor dynamics in a glaucoma patient.

PMID- 15741829
TI  - Physical activity level is associated with the O2 cost of walking in cerebral
      palsy.
AB  - PURPOSE: To determine, in children and adolescents with cerebral palsy (CP), the
      relationship between physical activity level (PAL) and i) oxygen cost of walking,
      and ii) peak VO2. METHODS: In 11 subjects (10.6-16.3 yr) with mild CP, PAL, the
      ratio of total energy expenditure to resting energy expenditure, was determined
      from 3 d of heart rate (HR) monitoring (field), with individual HR-VO2
      calibrations done in the lab. The oxygen cost of walking was measured during
      three 3-min walks on a treadmill at 60, 75, and 90% of each subject's fastest
      treadmill walking speed (FWS). Subjects also performed a maximal treadmill
      exercise test. Alpha was set at 0.05. RESULTS: One subject was an outlier and
      eliminated from all simple linear regression analyses. For the remaining 10
      subjects, PAL (1.37+/-0.18) was related (r=-0.70 to -0.84) to net VO2 at 60 and
      75% FWS (13.1+/-4.1 and 16.2+/-4.2 mL.kg.min), net VO2.m, averaged across the
      three speeds (0.32+/-0.23 mL.kg.m), and percent peak VO2 at all three speeds
      (54.5+/-21.5, 63.5+/-20.9, and 75.5+/-15.1%). PAL was not significantly related
      to net VO2 at 90% FWS (20.8+/-5.3 mL.kg.min) or to peak VO2 (34.0+/-9.2
      mL.kg.min). CONCLUSION: For this population, those with low PAL may also have a
      high oxygen cost of walking. These individuals' PAL was not related to their peak
      VO2. Further research is required to determine whether interventions that
      decrease the oxygen cost of walking also affect PAL and whether changes in PAL
      affect the oxygen cost of walking.

PMID- 15741830
TI  - Effect of ipratropium bromide on EIB in children depends on vagal activity.
AB  - PURPOSE: Ipratropium bromide (IB) has been used to prevent exercise-induced
      bronchoconstriction (EIB), but its effect varies among individuals. We
      hypothesized that such variability may reflect individual differences in vagal
      activity (VA), and therefore determined whether a correlation exists between VA
      and the effect of IB on EIB in 13.0 (+/-0.8)-yr-old children with asthma and
      documented EIB. METHODS: Subjects served as their own control and were tested on
      three occasions in an ambient temperature of 5 degrees C. Visit I included no
      treatment. In visits II and III (counterbalanced sequence) subjects inhaled
      either 500 microg IB or 0.9% NaCl as a placebo, 45 min before exercise
      provocation. Investigators and the subjects were blinded to the inhaled
      substance. VA was assessed by a 4-s exercise test (3). The ratio of resting ECG R
      R-interval at full inspiration to the lowest R-R interval during 4-s cycling was
      taken as an index of VA. Eight-minute cycling at constant work rate (HR=173+/-4
      bpm) at 5 degrees C was used to provoke EIB. A two-factor (treatment x time)
      repeated-measures ANOVA was used. RESULTS: The exercise-induced drop in FEV1 was
      similar in the three sessions. However, because the IB caused a 15.7+/-4.1
      increase in FEV1 preexercise, the postexercise values after a placebo or no
      treatment were consistently lower than after IB. The beneficial response to IB,
      compared with no treatment and with placebo, was positively correlated to VA (for
      FEV1: r=0.91, P=0.002; and r=0.90, P=0.002, respectively). CONCLUSION: We suggest
      that the therapeutic effect of IB on exercise-induced asthma may be related to
      vagal activity.

PMID- 15741831
TI  - Relationship between ankle-foot swelling and self-assessed function after ankle
      sprain.
AB  - PURPOSE: Decreasing swelling after ankle sprain is a main focus of treatment, as
      it is believed that swelling is related to function. The purpose of this study
      was to evaluate the relationship between ankle-foot swelling and self-assessed
      ankle function in the early period after ankle sprain. METHODS: Thirty-six
      individuals were tested for ankle-foot volume and self-assessed ankle function
      within days of spraining their ankle. Volumetric measurements of the injured and
      uninjured ankle-foot segment were taken with a foot and ankle volumeter. Stepwise
      linear regression analysis was performed, with function being the dependent
      variable, and the following variables included as independent variables: gender,
      age, body mass index, previous history of sprain in the injured ankle, and the
      volume difference between the injured and uninjured ankle-foot segment. RESULTS:
      None of the independent variables were significantly related to self-assessed
      function. Pearson's correlation coefficient for the injured minus uninjured ankle
      foot volume and self-assessed ankle function was -0.003. CONCLUSION: The results
      indicate that there is no relationship between ankle-foot swelling and self
      assessed ankle function in the early period after ankle sprain injury.

PMID- 15741832
TI  - Physical activity profiles of U.S. adults trying to lose weight: NHIS 1998.
AB  - PURPOSE: Physical activity is an integral part of weight control programs, but
      recommended amounts vary. The objectives of this study were to describe the
      prevalence and characteristics of those who reported using exercise as a weight
      loss strategy (N=14,716), and to determine the prevalence of meeting various
      institutionally recommended levels of physical activity (N=8538) among that
      population. METHODS: Data were obtained from the 1998 National Health Interview
      Survey, a face-to-face nationally representative household interview. Questions
      on leisure-time physical activity were analyzed using SUDAAN. RESULTS: Among
      those who reported trying to lose weight, 55% reported using exercise as a weight
      loss strategy alone, and of those, 58% reported eating fewer calories. The
      prevalence of using exercise as a weight loss strategy was directly associated
      with education and inversely associated with age and body mass index. Among those
      who reported using exercise as a weight loss strategy, 57% met the minimal 1998
      National Institutes of Health recommendation of >or=150 min.wk; 46% met the lower
      end of the 2001 American College of Sports Medicine recommendation of 200 min.wk;
      and 30% met the upper end for 300 min.wk. Only 19% met the 2002 Institute of
      Medicine recommendation of 420 min.wk. CONCLUSIONS: Despite the importance of
      physical activity in a weight loss program, only about half of the persons trying
      to lose weight reported using exercise. Even among those, only slightly more than
      half met the minimal recommendations for physical activity. Efforts are needed to
      aid those trying to lose weight to incorporate appropriate levels of physical
      activity into their weight loss strategy.

PMID- 15741833
TI  - Blood treatment influences the yield of apoptotic lymphocytes after maximal
      exercise.
AB  - PURPOSE: No systematic investigation has been reported assessing the effect of
      cell isolation processes on postexercise apoptosis. Therefore, the effect of cell
      isolation procedures on apoptosis was evaluated in this study. METHODS: Untrained
      healthy individuals participated (N=13). Blood samples obtained at rest and
      immediately after an incremental exercise test to exhaustion were partitioned
      into three treatments: 1) whole blood smears made immediately after the sample
      was obtained (WB), 2) cells subjected to density-gradient isolation before smears
      were made (ISO), and 3) samples allowed to sit at room temperature (i.e., time
      treated) before centrifugation and smearing (TT). Blood smears were stained using
      the May-Grunwald Giemsa procedure and lymphocytes were evaluated under a light
      microscope for characteristic features of apoptosis. Data were analyzed using a
      2x3 ANOVA. RESULTS: A significant interaction effect existed (P<0.0001) such that
      at rest, no difference was detected in the amount of lymphocyte apoptosis among
      WB, ISO, or TT samples. However, after exhaustive exercise, the amount of
      apoptotic lymphocytes was significantly greater in WB compared with ISO and TT
      samples (P<0.0001). CONCLUSION: Lymphocyte isolation results in a significant
      decrease in the percent of apoptotic lymphocytes after exhaustive exercise. This
      reduction is likely due to the time needed to isolate cells, rather than the
      isolation process itself. Because apoptosis is a time-sensitive process that
      occurs within minutes rather than hours, the length of time from initial sampling
      to the preparation of cells for assessment of apoptosis is critical and should be
      considered in future exercise studies.

PMID- 15741834
TI  - Mucosal IgA and URTI in American college football players: a year longitudinal
      study.
AB  - PURPOSE: The purpose of this study was: (a) to evaluate secretory immunoglobulin
      A (s-IgA) over a 12-month time period in college football players, and (b) to
      assess which of the commonly used standard methods of reporting s-IgA, either
      alone or in combination, serves as the best predictor of incidence of upper
      respiratory tract infection (URTI). METHODS: One hundred college-aged males (75
      varsity college football athletes, 25 nonfootball controls) were studied at eight
      points over a 12-month period. Resting mucosal IgA, protein and osmolality levels
      were determined from saliva using established procedures. In addition, incidence
      of URTI over the 12-month study duration was calculated from completed standard
      research logs. Repeated-measures ANOVA were conducted on the dependent variables
      and eight separate stepwise multiple regression analyses were conducted to
      predict the dependent variable "number of colds" by the independent variables, s
      IgA, saliva flow rate, secretion rate of s-IgA, protein, s-IgA:protein,
      osmolality and s-IgA:osmolality at each data collection point. RESULTS: There was
      a significant main effect for group, time, and the group x time interaction for s
      IgA, the secretion rate of s-IgA, and the number of colds. In the regression
      model, the only variable that made a significant contribution to the variance at
      all time points was the secretion rate of s-IgA. CONCLUSION: These findings
      suggest that a season of training in American football results in a significant
      decrease in both s-IgA and the secretion rate of s-IgA as well as an increase in
      the incidence of URTI. Among the various methods commonly employed to express s-
      IgA levels, the secretion rate of s-IgA may be the most useful clinical biomarker
      to predict the incidence of URTI.

PMID- 15741835
TI  - Exercise and hypercholesterolemia produce disparate shifts in coronary PKC
      expression.
AB  - INTRODUCTION: Sedentary lifestyle and high-fat, high-cholesterol diets are each
      associated with elevated risk for coronary heart disease (CHD); however, the
      mechanisms by which they increase risk are unclear. Specific PKC isoforms have
      been implicated in the development of CHD, regulation of coronary vasoreactivity,
      as well as exercise-induced cardioprotection. Thus, diet and physical inactivity
      may increase CHD risk by altering coronary protein kinase C (PKC) isoform
      profiles. PURPOSE: To determine whether coronary PKC isoform profiles are altered
      in a model of early CHD and whether exercise can prevent these changes. METHODS:
      Male and female Yucatan miniature swine were either fed a normal (NF) or high-fat
      (HF) diet (8 vs 46% kilocalories from fat) and remained sedentary (Sed) or were
      treadmill-trained (Ex) at 75% of; VO2max (6 mph, 60 min) for 16 wk. Groups were
      as follows: NFSed (N=8/N=7), NFEx (N=8/N=7), HFSed (N=8/N=7), and HFEx (N=8/N=7).
      Western blotting was performed on right coronary conduit artery (CCA) segments
      (>1 mm I.D.) to measure total protein levels of PKC-alpha, -betaI, -betaII, 
      delta, -epsilon, and -zeta. RESULTS: HF diet increased total cholesterol by more
      than sixfold with no increase in triglycerides. Hypercholesterolemia increased
      PKC-betaII and -epsilon protein levels in CCA of both male and female pig; Ex had
      no effect on this response. Ex-induced increases in PKC-betaI, PKC-delta, and PKC
      zeta were observed in HF male pigs. Female pigs had higher baseline amounts of
      PKC-alpha (25%), PKC-betaI (33%), PKC-betaII (39%), and PKC-epsilon (29%),
      whereas male pigs had higher amounts of PKC-delta (308%). Further analyses
      revealed a direct relationship between androgens and PKC-delta levels.
      CONCLUSION: Hypercholesterolemia and exercise exert disparate effects on coronary
      PKC expression. Observed sex differences in PKC protein profiles may also
      contribute to altered cardiovascular risk patterns in males versus females.

PMID- 15741836
TI  - Serotonin2C receptor blockade and thermoregulation during exercise in the heat.
AB  - PURPOSE: The effect of serotonin (5-HT)2C receptor blockade on the thermal
      response and exercise performance during exercise in a warm environment was
      examined. METHODS: Seven endurance-trained, but not heat-acclimatized,
      individuals (six males and one female) performed two 40-km time trials on a
      static cycle ergometer in a climatic chamber maintained at a mean (SD) ambient
      temperature of 35.5 (0.4) degrees C. The 5-HT2C receptor antagonist, pizotifen
      (1.5 mg), or placebo was administered orally on the evening before and again 6 h
      before exercise began. RESULTS: Resting rectal temperature (Tre) was higher
      (P=0.03) after pizotifen than placebo administration. Tre increased over time
      during exercise in both trials and was higher (P<0.05) during exercise in the
      pizotifen trial compared with the placebo trial from 40 to 60 min of exercise.
      There was no difference in Tre on completion of the time trial. The median times
      (range) required to complete the 40-km trials were 75.4 (69.0-82.5) and 76.1
      (68.0-82.1) min in the pizotifen and placebo trials, respectively. Despite a
      trend for speed to be slower in the later stages of exercise in the pizotifen
      trial, performance was not significantly influenced by administration of
      pizotifen (P=0.86). Resting serum prolactin (Prl) and cortisol concentrations
      were not different after pizotifen or placebo administration. In both trials,
      serum Prl and cortisol values increased over time and were increased relative to
      resting levels in both trials (P<0.01) but were not different between treatments.
      CONCLUSION: The present study suggests that 5-HT may influence body temperature
      via an effect on the 5-HT2C receptors, but this effect was not sufficient to
      influence performance.

PMID- 15741837
TI  - High-affinity growth hormone binding protein and acute heavy resistance exercise.
AB  - PURPOSE: The purpose of this investigation was to examine the influence of
      resistance training on circulating concentrations of growth hormone binding
      protein (GHBP) in response to acute heavy resistance exercise. METHODS: Using a
      cross-sectional experimental design, a group of resistance-trained men (RT, N=9,
      7.9+/-1.3 yr resistance training experience) and a group of untrained men (UT,
      N=10) performed an acute heavy resistance exercise protocol (AHREP) consisting of
      6 sets of 10 repetition maximum parallel squats. Blood samples were obtained 72 h
      before exercise, immediately before exercise, and 0, 15, 30, 45, and 60 min after
      exercise. RESULTS: Significant increases (P<0.05) in GHBP, immunoreactive growth
      hormone (iGH), and IGF-1 were observed in both subject groups after AHREP. There
      were no differences (P>0.05) between groups in GHBP at rest or after AHREP.
      However, RT exhibited a significantly greater iGH response to AHREP than UT
      subjects, and significantly higher IGF-1 values at rest and after exercise.
      Significant positive correlations were found between GHBP and BMI, body fat, and
      leptin in both groups. A significant positive correlation also was observed
      between resting leptin and GHBP values in UT but not RT subjects. CONCLUSIONS: In
      summary, these data indicate that resistance training does not increase blood
      GHBP. Nevertheless, the increases observed with IGF-1 concentrations in the
      resistance-trained subjects do suggest an apparent adaptation with the regulation
      of this hormone. If there was in fact an increase in GH sensitivity and GH
      receptor expression at the liver that was not detected by blood GHBP in this
      study, it may be possible that factors contributing to the circulating
      concentration of GHBP other than hepatocytes (e.g., leptin and adipocytes) may
      serve to mask training-induced increases in circulating GHBP of a hepatic origin,
      thus masking any detectable increase in GH receptor expression.

PMID- 15741838
TI  - Failure to repeatedly supercompensate muscle glycogen stores in highly trained
      men.
AB  - PURPOSE: It is not known whether it is possible to repeatedly supercompensate
      muscle glycogen stores after exhaustive exercise bouts undertaken within several
      days. METHODS: We evaluated the effect of repeated exercise-diet manipulation on
      muscle glycogen and triacylglycerol (IMTG) metabolism and exercise capacity in
      six well-trained subjects who completed an intermittent, exhaustive cycling
      protocol (EX) on three occasions separated by 48 h (i.e., days 1, 3, and 5) in a
      5-d period. Twenty-four hours before day 1, subjects consumed a moderate (6 g.kg)
      carbohydrate (CHO) diet, followed by 5 d of a high (12 g.kg.d)-CHO diet. Muscle
      biopsies were taken at rest, immediately post-EX on days 1, 3, and 5, and after 3
      h of recovery on days 1 and 3. RESULTS: Compared with day 1, resting muscle
      [glycogen] was elevated on day 3 but not day 5 (435+/-57 vs 713+/-60 vs 409+/-40
      mmol.kg, P<0.001). [IMTG] was reduced by 28% (P<0.05) after EX on day 1, but post
      EX levels on days 3 and 5 were similar to rest. EX was enhanced on days 3 and 5
      compared with day 1 (31.9+/-2.5 and 35.4+/-3.8 vs 24.1+/-1.4 kJ.kg, P<0.05).
      Glycogen synthase activity at rest and immediately post-EX was similar between
      trials. Additionally, the rates of muscle glycogen accumulation were similar
      during the 3-h recovery period on days 1 and 3. CONCLUSION: We show that well
      trained men cannot repeatedly supercompensate muscle [glycogen] after glycogen
      depleting exercise and 2 d of a high-CHO diet, suggesting that the mechanisms
      responsible for glycogen accumulation are attenuated as a consequence of
      successive days of glycogen-depleting exercise.

PMID- 15741839
TI  - Reduced heterogeneity of muscle deoxygenation during heavy bicycle exercise.
AB  - PURPOSE: This study evaluated heterogeneity of muscle O2 dynamics in a single
      muscle during bicycle exercise using an eight-channel near-infrared continuous
      wave spectroscopy (NIRcws) mapping system. METHODS: Nine healthy subjects
      performed bicycle exercise at fixed workloads of 20, 40, 60, 80, and 100% maximal
      workload for 5 min at each level. Muscle oxygenation in the vastus lateralis (VL)
      during and after each exercise was monitored using the NIRcws mapping system.
      Pulmonary O2 uptake and heart rate were monitored continuously during the
      experiment. Blood samples were taken to measure blood lactate concentration at 30
      s after each exercise stage. RESULTS: Half time reoxygenation, the time taken to
      reach a value of half-maximal recovery, was significantly delayed in distal sites
      compared with proximal sites of VL. Conversely, muscle deoxygenation for all
      measurement sites increased incrementally with higher exercise workloads, and no
      significant difference of deoxygenation level showed within each channel.
      However, relative dispersion of muscle deoxygenation during exercise
      significantly decreased when the workload increased. Moreover, relative
      dispersion of muscle deoxygenation between the subjects also decreased with an
      increase in the workload. CONCLUSION: Muscle deoxygenation in a single muscle was
      more heterogeneous at lower exercise workloads, and variations of the muscle
      deoxygenation heterogeneity between subjects were greater at lower exercise
      workloads.

PMID- 15741840
TI  - The chemoreflex: adult versus child comparison.
AB  - PURPOSE: Compare the influence of the chemoreflex on heart rate (HR) and blood
      pressure (BP) responses between children and adults. METHODS: Seventy children
      (35 boys and 35 girls) and 70 adults (35 men and 35 women) performed 30% maximal
      voluntary contraction static handgrip exercise (SHG) for 3 min, followed by 4 min
      of muscle ischemia and then 6 min of recovery, while HR and BP were measured.
      RESULTS: During 3 min of SHG, systolic BP (SBP) increased significantly more in
      men versus boys (23+/-9 vs 18+/-9%) and women versus girls (21+/-10 vs 15+/-7%),
      respectively. Diastolic BP (DBP) increased similarly during SHG in adults versus
      children. During SHG, HR increased similarly in males but significantly more in
      girls versus women (16+/-10 vs 11+/-9%), respectively. During occlusion, HR fell
      to baseline and remained through recovery in adults and children. Both SBP and
      DBP decreased similarly during the first minute of occlusion but remained
      significantly above baseline in adults and children. During the first minute of
      recovery, BP decreased to baseline in adults. In children, DBP decreased but
      remained significantly above baseline through recovery. SBP decreased in children
      during minute 1 of recovery yet remained significantly above baseline for 1-2 min
      in children. CONCLUSIONS: The muscle chemoreflex influence on HR and BP is
      similar in children and adults as evident in the return of HR to baseline, with a
      similar concomitant maintenance of BP above baseline during occlusion. When
      occlusion is released, BP returns to baseline in adults, whereas in children DBP
      remains significantly above baseline through recovery and SBP for 1-2 min. The
      differing BP response may be explained by a more active arterial chemoreflex in
      children.

PMID- 15741841
TI  - Oxidation of combined ingestion of maltodextrins and fructose during exercise.
AB  - PURPOSE: To determine whether combined ingestion of maltodextrin and fructose
      during 150 min of cycling exercise would lead to exogenous carbohydrate oxidation
      rates higher than 1.1 g.min. METHODS: Eight trained cyclists VO2max: 64.1 +/- 3.1
      mL.kg.min) performed three exercise trials in a random order. Each trial
      consisted of 150 min cycling at 55% maximum power output (64.2+/-3.5% VO2max)
      while subjects received a solution providing either 1.8 g.min of maltodextrin
      (MD), 1.2 g.min of maltodextrin + 0.6 g.min of fructose (MD+F), or plain water.
      To quantify exogenous carbohydrate oxidation, corn-derived MD and F were used,
      which have a high natural abundance of C. RESULTS: Peak exogenous carbohydrate
      oxidation (last 30 min of exercise) rates were approximately 40% higher with
      combined MD+F ingestion compared with MD only ingestion (1.50+/-0.07 and 1.06+/
      0.08 g.min, respectively, P<0.05). Furthermore, the average exogenous
      carbohydrate oxidation rate during the last 90 min of exercise was higher with
      combined MD+F ingestion compared with MD alone (1.38+/-0.06 and 0.96+/-0.07
      g.min, respectively, P<0.05). CONCLUSIONS: The present study demonstrates that
      with ingestion of large amounts of maltodextrin and fructose during cycling
      exercise, exogenous carbohydrate oxidation can reach peak values of approximately
      1.5 g.min, and this is markedly higher than oxidation rates from ingesting
      maltodextrin alone.

PMID- 15741842
TI  - Effects of exercise on heart rate variability: inferences from meta-analysis.
AB  - INTRODUCTION: Chronic exercise training produces a resting bradycardia that is
      thought to be due partly to enhanced vagal modulation. PURPOSE: The aim of the
      present study was to determine the effects of exercise training on heart rate and
      measures of heart rate variability associated with vagal cardiac modulation and
      to quantify the relationship between changes in these measures. METHODS: A random
      effects model of effect size (d) for change in high frequency (HF) power and RR
      interval was calculated. Within-group heterogeneity was assessed using the Q
      statistic. Where heterogenous effects were found, subgroup analyses were
      performed using the between-group Q statistic. RESULTS: A meta-analysis of 13
      studies measuring HF (N=322 cases) produced an overall effect size of d=0.48
      (C.I. 0.26-0.70, P=0.00003). Twelve studies (298 cases) reported a change in RR
      interval with an overall effect size of d=0.75 (C.I. 0.51-0.96, P<0.00001).
      Effect sizes for RR interval data were significantly heterogenous. Subgroup
      analysis revealed significantly smaller responses of RR interval to training in
      older subjects (P<0.1). Effect sizes for change in HF were homogenous, although a
      trend toward an attenuated response to training was exhibited in older subjects
      (P>0.10). Linear, quadratic, and cubic fits all revealed weak (P>0.05)
      relationships between effect sizes for change in HF and RR interval. DISCUSSION:
      Exercise training results in significant increases in RR interval and HF power.
      These changes are influenced by study population age. The smaller effect size for
      HF and weak relationship between HF and RR interval suggest factors additional to
      increased vagal modulation are responsible for training bradycardia.

PMID- 15741843
TI  - Is the effect of a countermovement on jump height due to active state
      development?
AB  - PURPOSE: To investigate whether the difference in jump height between
      countermovement jumps (CMJ) and squat jumps (SJ) could be explained by a
      difference in active state during propulsion. METHODS: Simulations were performed
      with a model of the human musculoskeletal system comprising four body segments
      and six muscles. The model's only input was STIM, the stimulation of muscles,
      which could be switched "off" or "on." After switching "on," STIM increased to
      its maximum at a fixed rate of change (dSTIM/dt). For various values of dSTIM/dt,
      stimulation switch times were optimized to produce a maximum height CMJ. From
      this CMJ, the configuration at the lowest height of the center of gravity (CG)
      was selected and used as static starting configuration for simulation of SJ.
      Next, STIM-switch times were optimized to find the maximum height SJ. RESULTS:
      Simulated CMJ and SJ closely resembled jumps of human subjects. Maximum jump
      height of the model was greater in CMJ than in SJ, with the difference ranging
      from 0.4 cm at infinitely high dSTIM/dt to about 2.5 cm at the lowest dSTIM/dt
      investigated. The greater jump height in CMJ was due to a greater work output of
      the hip extensor muscles. These muscles could produce more force and work over
      the first 30% of their shortening range in CMJ, due to the fact that they had a
      higher active state in CMJ than in SJ. CONCLUSION: The greater jump height in CMJ
      than in SJ could be explained by the fact that in CMJ active state developed
      during the preparatory countermovement, whereas in SJ it inevitably developed
      during the propulsion phase, so that the muscles could produce more force and
      work during shortening in CMJ.

PMID- 15741844
TI  - Lower-extremity gait kinematics on slippery surfaces in construction worksites.
AB  - PURPOSE: The purpose of this study was to investigate the lower-extremity
      kinematics when walking on potentially slippery surfaces in simulated
      construction worksite environments. METHODS: A survey was conducted to select two
      types of footwear, two floorings, and four contaminants to represent the local
      construction worksite environments, making 16 simulated conditions. A mechanical
      slip-resistance test was conducted to evaluate the slipping potential of the 16
      conditions by the value of the dynamic coefficient of friction. The 16 conditions
      were classified into three groups by slipping potential. Fifteen harnessed
      Chinese male subjects were instructed to walk and avoid slips on each of the 16
      simulated 5-m walkways 10 times at their natural cadence. The movements in the
      sagittal plane were videotaped, digitized, and analyzed by a motion analysis
      system. Gait pattern parameters were obtained. Lower-extremity kinematic data
      were time-normalized from foot strike (0% stance) to take-off (100% stance) and
      were extracted from foot strike to midstance (50% stance) at 10% stance
      intervals. RESULTS: ANOVA showed that with increased slipping potential, changes
      in gait pattern parameters included increased stance and stride time, shortened
      stride length, decreased propagation speed, and gentle heel strike. In lower
      extremity kinematic parameters, significant differences were found mainly at the
      ankle joint rather than the knee joint. CONCLUSION: Strategies to prevent slips
      included increased stance and stride time, shortened stride length, decreased
      propagation speed, and gentle heel strike. The ankle joint played the most
      important role in adaptation strategy. Such strategy included reducing range of
      motion, maintaining a stiff joint, and achieving flatfoot landing or a
      plantarflexed ankle joint during the first 10% stance.

PMID- 15741845
TI  - Electrostimulation training effects on the physical performance of ice hockey
      players.
AB  - PURPOSE: The aim of this study was to examine the influence of a short-term
      electromyostimulation (EMS) training program on the strength of knee extensors,
      skating, and vertical jump performance of a group of ice hockey players. METHODS:
      Seventeen ice hockey players participated in this study, with nine in the
      electrostimulated group (ES) and the remaining height as controls (C). EMS
      sessions consisted of 30 contractions (4-s duration, 85 Hz) and were carried out
      3x wk for 3 wk. Isokinetic strength of the knee extensor muscles was determined
      with a Biodex dynamometer at different eccentric and concentric angular
      velocities (angular velocities ranging from -120 to 300 degrees .s). Jumping
      ability was evaluated during squat jump (SJ), countermovement jump (CMJ), drop
      jump (DJ), and 15 consecutive CMJ (15J). Sprint times for 10- and 30-m skates in
      specific conditions were measured using an infrared photoelectric system.
      RESULTS: After 3 wk of EMS training, isokinetic torque increased significantly
      (P<0.05) for ES group in eccentric (-120 and -60 degrees .s) and concentric
      conditions (60 and 300 degrees .s), whereas vertical jump height decreased
      significantly (P<0.05) for SJ (-2.9+/-2.4 cm), CMJ (-2.1+/-2.0 cm), and DJ (
      1.3+/-1.1 cm). The 10-m skating performance was significantly improved (from
      2.18+/-0.20 to 2.07+/-0.09 s, before and after the 3-wk EMS period, respectively;
      P<0.05). CONCLUSION: It was demonstrated that an EMS program of the knee
      extensors significantly enhanced isokinetic strength (eccentric and for two
      concentric velocities) and short skating performance of a group of ice hockey
      players.

PMID- 15741846
TI  - Effect of distance feedback on pacing strategy and perceived exertion during
      cycling.
AB  - PURPOSE: The aim of this study was to investigate whether providing incorrect
      distance feedback would alter pacing strategies, perceived exertion, and heart
      rate during 20-km cycling time trials (TT). METHODS: Well-trained cyclists (N=15)
      performed a peak power output (PPO) test, familiarization trial, and four 20-km
      cycling TT during which they were provided with only distance feedback using 1-km
      distance splits. For the control trial, subjects received accurate feedback at
      each kilometer split. In the increase trial, they received inaccurate feedback at
      0.775 km for the first kilometer split with the distance increasing by 25 m each
      subsequent split up to 1.25 km in the final kilometer split. For the decrease
      trial, inaccurate feedback was provided at 1.25 km for the first kilometer split
      with the distance decreasing by 25 m each subsequent split up to 0.775 km in the
      final split. For the random trial, distance splits were randomized. RESULTS: No
      significant differences were found in the finishing times between trials. Pacing
      strategies were unaltered as suggested by similar power output profiles during
      all trials. RPE scores were also similar for all trials. However, average heart
      rate varied significantly between trials (P<0.05). CONCLUSIONS: These results
      suggest that exercise performance, pacing strategy, and RPE during a 20-km
      cycling TT are not altered by incorrect distance feedback. The data supported the
      existence of a pacing strategy that is set before exercise and that is unaffected
      by external distance feedback.

PMID- 15741847
TI  - Motivation and burnout among top amateur rugby players.
AB  - INTRODUCTION: Self-determination theory has proven to be a useful theoretical
      explanation of the occurrence of ill-being on a variety of accounts. Self
      determination theory may also provide a useful explanation of the occurrence of
      athlete burnout. To date, limited evidence exists to support links between
      motivation and burnout. PURPOSE: To examine relationships and potential causal
      directions among burnout and types of motivation differing in degree of self
      determination. METHOD: Data were collected on burnout using the Athlete Burnout
      Questionnaire and Sport Motivation Scale from 392 top amateur male rugby players.
      Structural equation modeling procedures were employed to evaluate a measurement
      model and three conceptually grounded structural models. One conceptual model
      specified concomitant (noncausal) relationships between burnout and motivations
      varying in self-determination. The other conceptual models specified causal
      pathways between burnout and the three motivation variables considered in the
      investigation (i.e., intrinsic motivation, external regulation, and amotivation).
      RESULTS: Within the models, amotivation, the least self-determined type of
      motivation, had a large positive association with burnout. Externally regulated
      motivation had trivial and nonsignificant relationships with burnout. Self
      determined forms of motivation (i.e., intrinsic motivation) exhibited significant
      negative associations with burnout. CONCLUSIONS: Overall the results support the
      potential utility of a self-determination theory explanation of burnout. As all
      models displayed reasonable and comparable fits, further research is required to
      establish the nature (concomitant vs directional causal vs reciprocal causal) of
      the relationship between burnout and motivation.

PMID- 15741848
TI  - Enjoyment mediates effects of a school-based physical-activity intervention.
AB  - PURPOSE: The study evaluated whether targeted changes in factors influencing
      enjoyment of physical education (PE), physical activity enjoyment, and self
      efficacy beliefs about participating in physical activity mediated the effect of
      the Lifestyle Education for Activity Program (LEAP) intervention on participation
      in physical activity. METHODS: High schools (N=24) paired on enrollment size,
      racial composition, urban or rural location, and class structure were randomized
      into control (N=12) or experimental (N=12) groups. Of the 4044 girls enrolled and
      eligible, 2087 (51.6%) participated in the measurement component of the study.
      There were 1038 girls in the control group and 1049 girls in the experimental
      group. INTERVENTION: LEAP was a comprehensive school-based intervention
      emphasizing changes in instruction and school environment designed to increase
      physical activity among black and white adolescent girls. It was organized
      according to the Coordinated School Health Program and included a PE component
      with core objectives of promoting enjoyment of PE, physical activity enjoyment,
      and self-efficacy. RESULTS: Latent variable structural equation modeling
      indicated that: 1) the intervention had direct, positive effects on physical
      activity and factors influencing enjoyment of PE, which subsequently explained
      the effects of increased physical activity enjoyment and self-efficacy on
      increased physical activity; and 2) an additional, indirect effect of physical
      activity enjoyment on physical activity operated by an influence on self
      efficacy. CONCLUSIONS: Increases in enjoyment partially mediated the positive
      effect of the LEAP intervention. To our knowledge, we have provided the first
      experimental evidence from a randomized controlled trial linking increased
      enjoyment with increased physical activity among black and white adolescent
      girls.

PMID- 15741849
TI  - Validity and reliability of the Fels physical activity questionnaire for
      children.
AB  - PURPOSE: The aim was to evaluate the reliability and validity of the Fels
      physical activity questionnaire (PAQ) for children 7-19 yr of age. METHODS: A
      cross-sectional study was conducted among 130 girls and 99 boys in elementary
      (N=70), middle (N=81), and high (N=78) schools in rural Maryland. Weight and
      height were measured on the initial school visit. All the children then wore an
      Actiwatch accelerometer for 6 d. The Fels PAQ for children was given on two
      separate occasions to evaluate reliability and was compared with accelerometry
      data to evaluate validity. RESULTS: The reliability of the Fels PAQ for the
      girls, boys, and the elementary, middle, and high school age groups range was
      r=0.48-0.76. For the elementary school children, the correlation coefficient
      examining validity between the Fels PAQ total score and Actiwatch (counts per
      minute) was 0.34 (P=0.004). The correlation coefficients were lower in middle
      school (r=0.11, P=0.31) and high school (r=0.21, P=0.006) adolescents. The sport
      index of the Fels PAQ for children had the highest validity in the high school
      participants (r=0.34, P=0.002). CONCLUSION: The Fels PAQ for children is
      moderately reliable for all age groups of children. Validity of the Fels PAQ for
      children is acceptable for elementary and high school students when the total
      activity score or the sport index is used. The sport index was similar to the
      total score for elementary students but was a better measure of physical activity
      among high school students.

PMID- 15741850
TI  - How do endurance runners actually train? Relationship with competition
      performance.
AB  - PURPOSE: To quantify the relationship between total training load and running
      performance during the most important competitions of the season (national cross
      country championships, 4.175- and 10.130-km races). METHODS: Eight well-trained,
      subelite endurance runners (age (mean+/-SD): 23+/-2 yr; VO2max: 70.0+/-7.3
      mL.kg.min) performed a maximal cardiorespiratory exercise test before the
      training period to determine ventilatory threshold (VT) and respiratory
      compensation threshold (RCT). Heart rate was continuously recorded using
      telemetry during each training session over a 6-month macrocycle, designed to
      achieve peak performance during the aforementioned cross-country races, lasting
      from late August to the time that these races were held, that is, mid-February.
      This allowed us to quantify the total cumulative time spent in three intensity
      zones calculated as zone 1 (low intensity, lower than the VT); zone 2 (moderate
      intensity, between VT and RCT); and zone 3 (high intensity, above the RCT).
      RESULTS: Total training time in zone 1 (4581+/-979 min) was significantly higher
      (P<0.001) than that accumulated in zones 2 (1354+/-583 min) and 3 (487+/-154
      min). Total time in zone 2 was significantly higher than time in zone 3 (P<0.05).
      A correlation coefficient of r=-0.79 (P=0.06) and r=-0.97 (P=0.008) was found
      between the total training time spent in zone 1 and performance time during the
      short and long cross-country races, respectively. CONCLUSIONS: Our findings
      suggest that total training time spent at low intensities might be associated
      with improved performance during highly intense endurance events, especially if
      the event duration is approximately 35 min. Interventional studies (i.e.,
      improving or reducing training time in zone 1) are needed to corroborate our
      findings and to elucidate the physiological mechanisms behind them.

PMID- 15741851
TI  - Recovery during high-intensity intermittent anaerobic exercise in boys, teens,
      and men.
AB  - PURPOSE: This study examined the effects of age on recovery of peak torque of
      knee extensors (PTEX) and flexors (PTFL), and total work (TW) during high
      intensity intermittent 30-s (HI30) and 60-s (HI60) exercise in boys (N=19; age,
      11.4+/-0.5 yr), teens (N=17; age, 14.7+/-0.4 yr), and men (N=18; age, 24.1+/-2.0
      yr). METHODS: Each age group's subjects were subdivided to participate in an HI30
      or an HI60 protocol. The HI30 involved 4x18 maximal knee extensions and flexions
      (1-min rest between sets), and the HI60 comprised of 2x34 reps (2-min rest). PTEX
      (N.m.kg), PTFL (N.m.kg), and TW (J.kg) were recorded at each set. The percent
      recovery of PTEX, PTFL, and TW was calculated as percent of the value achieved in
      the first set. RESULTS: In HI60, the percent recovery for PTEX, PTFL, and TW
      after the first set was higher in boys compared with teens and men (P<0.01). In
      HI30, the percent recovery for PTEX, PTFL, and TW was higher in boys compared
      with men in all sets (P<0.01), and in teens compared with men in the last two
      sets (P<0.05). The percent recovery of PTFL and TW was higher in boys compared
      with teens in the last two sets (P<0.05). Lactate increase was most pronounced in
      men, less pronounced in teens, and least pronounced in boys (P<0.01). Heart rate
      recovered faster in boys compared with teens and men in both protocols (P<0.05).
      CONCLUSIONS: The recovery was faster in boys than in teens and men during HI30
      and HI60, as evident by the greater percent recovery in boys for a given time.
      Furthermore, it appears that the rate of recovery during HI30 and HI60 anaerobic
      exercise is maturity dependent.

PMID- 15741852
TI  - The accuracy of pedometer steps and time during walking in children.
AB  - PURPOSE: To determine the accuracy of pedometer step counts and time during self
      paced walking (SPW) and treadmill walking in children (5-11 yr). Two pedometers
      were assessed during SPW: Digiwalker SW-200 (DW200) and Walk4Life 2505 (WL), and
      four pedometers during treadmill walking: DW200, WL, Digiwalker SW-701 (DW701),
      and the Sun TrekLINQ (SUN). METHODS: Ten boys (8.3+/-1.5 yr) and 10 girls (8.9+/
      1.7 yr) completed three single-lap SPW trials around an outdoor athletic track.
      Treadmill walking was performed at the following speeds: 40, 54, 67, 80, and 94
      m.min-1. During treadmill walking, each model was measured on the right and left
      sides. Pedometer steps and time and observed steps and time were recorded for all
      trials. RESULTS: Across SPW trials, there was high agreement on observed steps
      for both the DW200 and WL (intraclass correlation coefficient (ICC) 0.985-0.997).
      For treadmill walking, at <or=54 m.min-1, low interunit agreement (ICC<or=0.746)
      and low agreement between pedometer steps and observed steps (ICC<or=0.720) were
      detected for all models. For pedometer time, the WL exhibited a high level of
      agreement with observed during SPW (ICC 0.997-0.998). During treadmill walking,
      the WL was within 5.3% of actual time across all speeds, whereas time with the
      SUN did not come within 5% agreement until 80 m.min-1. CONCLUSIONS: Findings are
      consistent with adult studies with step count underestimation during slow (<or=54
      m.min-1) walking. Low interunit agreement at slow speeds suggests variations in
      step count registry within models. The accuracy of time (WL), independent of step
      count accuracy and speed, suggests that time might be used in addition to steps
      to quantify the physical activity behavior of children.

PMID- 15741853
TI  - Power prediction equations.

PMID- 15741857
TI  - Doubtful 24-h urinary cortisol/cortisone ratio to monitor training effects in
      elite swimmers.

PMID- 15741859
TI  - Finding strength in numbers.

PMID- 15741865
TI  - Managing UTIs in older adults.

PMID- 15741866
TI  - Using a wound assessment form.

PMID- 15741867
TI  - On alert for monkeypox.

PMID- 15741868
TI  - How to bring evidence-based practice to the bedside.

PMID- 15741874
TI  - Documenting a transfusion reaction.

PMID- 15741875
TI  - Factoring the risks of factor V Leiden.

PMID- 15741876
TI  - Tips for safe, accurate occult blood testing.

PMID- 15741892
TI  - Conquering PAIN: have you tried these new techniques?

PMID- 15741894
TI  - A gift for Joseph.

PMID- 15741895
TI  - Nurse against nurse: how to stop horizontal violence.

PMID- 15741896
TI  - Wake-up call for sleep apnea.

PMID- 15741897
TI  - Managing preeclampsia buys time for a safe delivery.

PMID- 15741898
TI  - Patient education series. Anemia.

PMID- 15741899
TI  - Teaching your patient to use a peak flowmeter.
AB  - Monitoring peak expiratory flow rates and keeping a daily diary can help him
      manage his asthma better.

PMID- 15741900
TI  - Mr. Gomez had a different agenda...

PMID- 15741901
TI  - Call a stroke code!

PMID- 15741905
TI  - Ease a child's anxiety during PICC insertion--without sedation.

PMID- 15741909
TI  - You routinely administer combination drugs...

PMID- 15741910
TI  - Cardiac tamponade.

PMID- 15741911
TI  - [Epidemiology, an interdisciplinary crossroads].

PMID- 15741912
TI  - [Contribution of unvaccinated siblings to a measles outbreak in Switzerland].
AB  - BACKGROUND: A measles outbreak occurred in Geneva between March and July 2003. An
      investigation was conducted to determine its magnitude, identify predominant
      modes of transmission, and assess disease outcome. METHODS: In Switzerland,
      measles notification has been mandatory for physicians since 1999 and
      laboratories since 1988. All cases were investigated and followed up by
      interviewing physicians using a standardized questionnaire. Viral genotype was
      determined for 4 cases using a saliva specimen processed at the Robert Koch
      Institute, Berlin. Geographic distribution of cases and vaccination coverage were
      compared. RESULTS: Overall, 54 cases were notified. Fifty-three cases were
      between 10 and 19 years of age. Ninety-four percent (n = 46) of 49 cases with
      known vaccination status were not vaccinated and none were fully immunized (2
      doses). Measles complications occurred among 19% (n = 7) of the 36 patients with
      follow up information: pneumonia (n = 4, combined with pericarditis and hepatitis
      in one case) and bronchitis (n = 3). Three persons were hospitalized. No
      complication was reported among 3 persons partially vaccinated (1 dose). The
      virus belonged to genotypes D8 and D5. Five separate clusters of related cases
      included 74% of all cases. Transmission mainly occurred within families (43% of
      all cases) and school (28%). Two of the most affected areas had measles
      vaccination coverage well below the cantonal average. CONCLUSION: Low vaccination
      coverage combined with clusters of unvaccinated household contributed to
      continued virus circulation and represents a threat to the canton of Geneva as
      new outbreaks of measles may reoccur.

PMID- 15741913
TI  - [Joint modeling of quantitative longitudinal data and censored survival time].
AB  - BACKGROUND: In epidemiology, we are often interested in the association between
      the evolution of a quantitative variable and the onset of an event. The aim of
      this paper is to present a joint model for the analysis of Gaussian repeated data
      and survival time. Such models allow, for example, to perform survival analysis
      when a time-dependent explanatory variable is measured intermittently, or to
      study the evolution of a quantitative marker conditionally to an event. METHODS:
      They are constructed by combining a mixed model for repeated Gaussian variables
      and a survival model which can be parametric or semi-parametric (Cox model).
      RESULTS: We discuss the hypotheses underlying the different joint models proposed
      in the literature and the necessary assumptions for maximum likelihood
      estimation. The interest of these methods is illustrated with a study of the
      natural history of dementia in a cohort of elderly persons.

PMID- 15741915
TI  - [Multiple comparison procedures: principles, limits. Applications to microarray
      phenotype-genotype analysis].
AB  - BACKGROUND: When analysing data which simultaneously implicate a large number of
      statistical tests, one of the main problems is to take into account the
      multiplicity of these tests. The huge amount of comparisons done in studies of
      which the aim is to detect, using microarray, genes whose transcriptional changes
      are related to a biological or clinical outcome leads to a renewed interest for
      the multiple comparisons problem. However, this problem concerns many other
      fields such as psychometry, epidemiology, genetics. RESULTS: First, we introduce
      the multiple comparison framework. Then, we present the main procedures based on
      a global error rate called the "Family Wise Error Rate" (FWER) and those based on
      a false discovery rate expectancy (the "False Discovery Rate" (FDR) and the
      "positive False Discovery Rate" (pFDR)). Next, we apply the different procedures
      on a real dataset from a breast carcinoma study. Finally, we discuss the main
      results and we present guidelines for the use of these procedures.

PMID- 15741914
TI  - [Prescription of high dose buprenorphine by general practitioners].
AB  - BACKGROUND: Since 1996, prescribing buprenorphine in high dosage as a drug
      maintenance treatment has been allowing French general practitioners to undertake
      drug addicts with a pharmacological support. In France, buprenorphine
      prescriptions seem to spread over general practitioners (buprenorphine was given
      to 74,300 patients in 2001). This paper assesses the different factors associated
      with buprenorphine prescription by general practitioners and with the different
      degrees of general practitioners' commitment in actually caring drug addicts with
      the help of buprenorphine. METHODS: Two representative samples of private general
      practitioners, either prescribing buprenorphine (345 over a population of 876) or
      not prescribing (355 over a population of 1380) have been questioned through a
      phone interview in the department of South-Eastern France in November and
      December 2002. Samples have been constituted with the help of a random stratified
      survey according to sex, age and volume of services (acceptance rate: 65.5%).
      Survey data have been completed with general practitioners' activity data from
      Health Insurance and local socioeconomic data from Insee. RESULTS: 37.5% of
      general practitioners have at least once prescribed buprenorphine during the
      considered period, but only 26% of the prescribers treated 75% of patients.
      Prescribers are most often men, younger than 49 years, working in the fixed fees
      sector and having group practice. They are also most often members of a health
      care network, trained for drug maintenance treatments and, from an individual
      point of view, have relatives suffering cancer, or having HIV, or hepatitis C, or
      who are drug addicts. Low socioeconomic status of the area where GPs exert seems
      to be particularly associated with general practitioners' prescription of
      buprenorphine. CONCLUSION: Data handled in this paper show that supply of
      substitutive treatments is concentrated among a reduced number of general
      practitioners and in particularly deprived geographic areas. Workload in deprived
      areas combined to great professional commitment in maintenance treatment reveals
      unexpected and unwanted specialisation behaviours by general practitioners, as
      well as more isolated behaviours by general practitioners who do not ask for
      particular training program or help by colleagues. These results question the
      consistency of the general framework of support to general practitioners proposed
      by health authorities with general practitioners actual practice and needs.

PMID- 15741916
TI  - [Adjustment for energy intake in the assessment of dietary risk factors].
AB  - Epidemiologic studies assessing the association between health status and
      nutritional factors raise the issue of adjusting for energy intake. Indeed, as
      most nutrients are highly correlated with energy intake which can itself be
      associated with disease risk, energy intake needs to be adjusted for upon
      assessing the effect of a specific nutrient. To avoid problems of estimation and
      interpretation incurred by the use of the standard method which rests on directly
      adjusting for energy intake, several other methods have been suggested. Namely,
      the density method uses the ratio of nutrient intake over total energy intake,
      the residual method relies on the residuals from the regression of nutrient
      intake on total energy intake, and the partition method fits energy from the
      nutrient and energy from other sources. These methods yield estimates of
      different effects but do not allow direct estimation of specific nutrient
      effects. Estimated effects combine specific and generic energy effects of
      nutrients and reflect effects of adding or substituting one nutrient for another.
      We review and apply these methods to the assessment of the association between
      protein intake and colorectal adenoma occurrence in the E3N-EPIC cohort. This
      example illustrates how considering findings from all of these methods rather
      than one single method can lead to a more in-depth understanding of such
      associations and provide useful guidance for nutritional recommendations.

PMID- 15741917
TI  - [The first Tunisian cardiovascular diseases register: processes and results].
AB  - BACKGROUND: In Tunisia, cardiovascular diseases are the leading causes of death
      (30%) and a few studies conducted in the population have demonstrated that the
      level of their risk factors is increasing. For policy makers, the health system
      impact of these diseases is currently a crucial issue. The National Public Health
      Institute has identified the implementation of a morbidity register as a
      priority. METHODS: A CVD morbidity register is implemented since 2001, in 3
      different geographical populations having contrasted levels of health status
      (Tunis, Ariana and Ben Arous). The 3 regions are covering about 2 millions
      inhabitants which is the fifth of the overall Tunisian population. All coronary
      heart events occurring among adults 25 years old and above in the 3 populations
      are recorded. The diagnosis of events, case fatality and classification are
      defined according to MONICA criteria. The data are recorded from public and
      private hospitals, death certificates and autopsies. RESULTS: During the year
      2001, the total number of myocardial infarction events was estimated at 942: in
      men, the age-standardized rates were 163.8/100000 in Tunis population vs. 161.9
      in Ariana and 170.5 in Ben Arous. In women, the rates were respectively 43.4,
      61.1 and 44.6. Medical causes of death registration was the most crucial problem
      in spite of the implementation of the death certificate designed according to WHO
      model. Specific surveys for clinical assessment and surveillance of risk factors
      were conducted in the register populations. CONCLUSION: It is the first time that
      data on coronary heart disease incidence and fatality are available in Tunisia
      through this experience which highlights the practical difficulties experienced
      in registering and coding coronary events in a developing country. The data
      source quality should be improved and the register should be integrated in the
      local health system.

PMID- 15741918
TI  - Infections and atopy: an exploratory study for a meta-analysis of the "hygiene
      hypothesis".
AB  - BACKGROUND: According to the "hygiene hypothesis" selected allergic diseases
      could be prevented by exposure to infectious agents during early childhood.
      METHODS: This study was performed to assess the feasibility of a future meta
      analysis on the "hygiene hypothesis" and atopic diseases. Differences concerning
      the potential association with a history of infectious events, in terms of
      magnitude and homogeneity of global risk estimates between the three major atopic
      diseases (i.e. atopic dermatitis, asthma and allergic rhinitis) were examined. We
      conducted a preliminary analysis on a sample of articles published on this topic
      and cited in a recent and authoritative review. RESULTS: The ranges of relative
      risks estimates (between 0.6 and 0.8) were similar for atopic dermatitis,
      allergic rhinitis and asthma. Compared with asthma and allergic rhinitis,
      reported global risk estimates were more stable for atopic dermatitis (lowest
      heterogeneity). Our analysis suggests that three main categories of indirect
      markers of exposure to infection can be identified: 1) geographical gradient, 2)
      indices of potential contact with infectious agents (such as number of siblings)
      and 3) history of infectious events. CONCLUSIONS: In this exploratory study, we
      chose articles cited in a single review and obtained a preliminary quantification
      of the association between infections and atopic diseases. The association with
      indirect markers of infection corresponded to 20% protection for atopic
      dermatitis, 30% for allergic rhinitis and 40% for asthma. In a subsequent meta
      analysis, diseases should be considered separately and differences between types
      of exposures should be taken into account as one of the major end-points, with
      attention to time since exposure and disease onset.

PMID- 15741920
TI  - The deadly triangle of anemia, renal insufficiency, and cardiovascular disease:
      implications for prognosis and treatment.
AB  - Recently there has been considerable interest in the associations between blood
      hemoglobin (Hb) level, renal function, and cardiovascular disease. Anemia is a
      common feature of end-stage renal disease, but it also accompanies lesser degrees
      of chronic kidney disease (CKD). The degree of anemia roughly approximates the
      severity of CKD. Anemia seen in diabetes has been linked to diabetic nephropathy;
      however, diabetes itself affects the hematologic system in several ways. Anemia
      is associated with left ventricular hypertrophy, cardiovascular morbidity,
      progressive loss of kidney function, and poor quality of life. Anemia seems to
      act as a mortality multiplier; that is, at every decrease in Hb below 12 g/dL,
      mortality increases in patients with CKD, cardiovascular disease, and those with
      both. Unlike blood transfusion, treatment of anemia with exogenous erythropoietin
      in patients with cardiorenal disease has shown promise in reducing morbidity and
      in improving survival and quality of life. Increasing the Hb level from less than
      10 g/dL to 12 g/dL has resulted in favorable changes in left ventricular
      remodeling, improved ejection fraction, improved functional classification, and
      higher levels of peak oxygen consumption with exercise testing. Clinical trials
      are underway to test the role of erythropoietin in patients with CKD and in
      patients with heart failure.

PMID- 15741921
TI  - The emerging role of percutaneous intervention in adults with congenital heart
      disease.
AB  - Adults with congenital heart disease (CHD) constitute a patient population that
      has grown rapidly, due to advances in diagnosis and treatment of children with
      CHD. Though ideally served by cardiologists with advanced training in congenital
      conditions, adults with CHD often receive the majority of their care from primary
      care physicians and general cardiologists. These patients often have unique
      clinical presentations. An understanding of available therapeutic modalities can
      assist clinicians in the timing of subspecialty referral. This review focuses on
      the unique challenges of cardiac catheterization and the role of percutaneous
      interventions in adults with CHD.

PMID- 15741922
TI  - Aortic stenosis: physics and physiology--what do the numbers really mean?
AB  - Cardiac catheterization and Doppler echocardiography are two methods used to
      measure transvalvular gradients and valve area in the assessment of aortic
      stenosis severity. Although both approaches are based on the same hemodynamic
      concepts and report data using the same units of measure, each method measures
      pressure drop or gradient at a different place; hence they produce fundamentally
      different quantities. Likewise, cardiac catheterization formulas for valve area
      attempt to obtain the anatomic area whereas the Doppler continuity equation
      reports the area to which flow is constricted. To use these two methods
      appropriately, it is necessary to understand the underlying hemodynamic
      principles and the effects of the methods of measurement on the values obtained.
      This article examines these variables and shows how they affect the reported
      gradients and valve areas and how differences can affect clinical application.

PMID- 15741924
TI  - The emerging use of 16- and 64-slice computed tomography coronary angiography in
      clinical cardiovascular practice.
AB  - Multi-slice computed tomography (MSCT) coronary angiography is an imaging
      modality that can identify patients with both soft and hard plaque, supplementing
      the information gleaned from an ordinary coronary calcium scan and classic risk
      factor assessment. Clinicians now have the tools to identify the presence of
      coronary artery disease (CAD) in the presymptomatic phase, as well as those
      needed to help identify the etiology of pain syndromes in patients presenting
      with atypical or obscure symptoms and who may be suffering from obstructive CAD,
      aortic dissection, pulmonary emboli, or other pathologic processes. There is
      considerable training and practice involved in developing the skills necessary to
      convert raw information from a CT scanner to optimal diagnostic images; however,
      MSCT provides important diagnostic information in a faster, less expensive, more
      patient-friendly, and safer manner than conventional coronary angiography. The
      following 2 cases describe the use of MSCT coronary angiography in patients with
      atypical symptoms and exemplify the use of this technology in a clinical setting.

PMID- 15741925
TI  - The PEACE trial: ACE inhibitors and coronary artery disease.

PMID- 15741926
TI  - Novel serum markers for risk prediction in acute coronary syndromes.

PMID- 15741927
TI  - Differentiating functional constipation from constipation-predominant irritable
      bowel syndrome: management implications.
AB  - Symptoms of constipation are commonly seen in medical practice. Once other
      medical causes have been excluded, distinguishing patients who have constipation
      predominant irritable bowel syndrome (IBS) from those with functional
      constipation has been considered useful in terms of planning management. However,
      the criteria used to distinguish IBS from functional constipation are arguably
      arbitrary, and the availability of new therapeutic approaches may render such
      distinctions of little practical relevance. In this article, the author presents
      a review of the management implications of differentiating constipation
      predominant IBS from functional constipation.

PMID- 15741928
TI  - New concepts in anti-tumor necrosis factor therapy for inflammatory bowel
      disease.
AB  - Crohn's disease is a T helper type 1 response immune disease characterized by
      increased production of interleukin-12 tumor necrosis factor-a (TNF-a), and
      interferon-g. Clinical trials have demonstrated that inhibition of TNF is
      effective for the treatment of Crohn's disease. Adverse events reported in
      patients treated with anti-TNF agents include immunogenicity, acute infusion
      reactions, delayed hypersensitivity-type reactions, autoimmune diseases including
      drug-induced lupus and demyelination, and infection. This article reviews new
      concepts in the treatment of Crohn's disease and ulcerative colitis with a
      variety of anti-TNF biologic therapies: infliximab, adalimumab, CDP870, CDP571,
      etanercept, and onercept.

PMID- 15741929
TI  - Rifaximin: a nonabsorbed oral antibiotic.
AB  - Rifaximin is a rifamycin analogue with a broad spectrum of activity similar to
      that of rifampin; however, because it is poorly absorbed in the gastrointestinal
      tract, the focus of its development has been on intestinal infections and
      diseases. This agent has proven to be as effective as ciprofloxacin in treating
      travelers' diarrhea due to Escherichia coli, although it is ineffective in
      treating infections due to Campylobacter jejuni. Other potential uses for
      rifaximin in gastroenterologic disorders include treatment of hepatic
      encephalopathy, intestinal gas and gas-related symptoms, diverticular disease,
      intestinal bacterial overgrowth, pouchitis, ulcerative colitis, and active
      Crohn's disease. This article highlights several studies demonstrating the
      efficacy of rifaximin in treating travelers' diarrhea as well as other
      gastrointestinal diseases and discusses the drug's pharmacokinetics, indications,
      contraindications, warnings, precautions, adverse reactions, and dosing.

PMID- 15741932
TI  - Gastroesophageal reflux disease. Recent findings in GERD research.

PMID- 15741933
TI  - Editor's commentary.

PMID- 15741934
TI  - Samuel Torrey Orton Award to Jack M. Fletcher: citation.
AB  - In recognition of your commitment to effective reading instruction through your
      dedicated research into language development and other cognitive skills in
      children and adults with learning and attention difficulties.

PMID- 15741935
TI  - The development of children at familial risk for dyslexia: birth to early school
      age.
AB  - Children at risk for familial dyslexia (n = 107) and their controls (n = 93) have
      been followed from birth to school entry in the Jyvaskyla Longitudinal study of
      Dyslexia (JLD) on developmental factors linked to reading and dyslexia. At the
      point of school entry, the majority of the at-risk children displayed decoding
      ability that fell at least 1 SD below the mean of the control group. Measures of
      speech processing were the earliest indices to show both group differences in
      infancy and also significant predictive associations with reading acquisition. A
      number of measures of language, including phonological and morphological skill
      collected repeatedly from age three, revealed group differences and predictive
      correlations. Both the group differences and the predictive associations to later
      language and reading ability strengthened as a function of increasing age. The
      predictions, however, tend to be stronger and the spectrum of significant
      correlations wider in the at-risk group. These results are crucial to early
      identification and intervention of dyslexia in at-risk children.

PMID- 15741936
TI  - Emerging phonological awareness differentiates children with and without familial
      risk for dyslexia after controlling for general language skills.
AB  - Emerging phonological awareness was compared in two groups of 3.5-year-old
      children belonging to the Jyvaskyla Longitudinal Study of Dyslexia (JLD):
      children with familial risk of dyslexia (at-risk group n = 98) and children
      without such risk (control group n = 91). Four computer animated tasks were used:
      Word-level and Syllable-level Segment Identification, Synthesis, and Continuation
      of Phonological Units. The control group children manifested higher mastery than
      children in the at-risk group in phonological awareness, and the proportion of
      children with a low phonological awareness mean score was 2.5 times higher in the
      at-risk group than in the control group. In both groups, phonological awareness
      at 3.5 years was predicted by early language skills assessed between 14 and 26
      months of age, and it was also associated with concurrent language. The
      difference between the at-risk and control group at 3.5-year in phonological
      awareness remained significant, even when the effect of other language skills
      such as productive and receptive vocabulary, and mastery of inflections, measured
      both at earlier ages and concurrently were controlled for. Our findings indicate
      that familial risk for dyslexia is reliably reflected in emerging phonological
      awareness already at this early age and it can be assessed independently of other
      language skills.

PMID- 15741937
TI  - Remembering Dr. Anne E. Fowler editor, Annals of Dyslexia, 1994-1999.

PMID- 15741938
TI  - Relationships of naming skills to reading, memory, and receptive vocabulary:
      evidence for imprecise phonological representations of words by poor readers.
AB  - The main hypotheses addressed in the research were (1) whether imprecision in the
      phonological representations of lexical items underlies the impaired expressive
      naming abilities of disabled readers, and (2) whether weak verbal memory might
      mediate the relationship between naming and reading skills. From samples of 93
      first graders and 67 fourth graders, extreme groups of good and poor readers were
      identified and compared on measures of receptive vocabulary, expressive naming,
      acceptability judgments for variants of object names, imitation and correction of
      naming errors by another speaker, pseudoword repetition, and long-term memory.
      Performance was generally better by older than younger students and by good than
      poor readers at each age, with little interaction between grade and reader group.
      The results indicated that for both good and poor readers, imprecise phonological
      knowledge, especially about long words, contributed to children's difficulties on
      all naming tasks. Memory differences, however, appeared to play only a minor role
      in explaining the strong association between naming and reading.

PMID- 15741939
TI  - Slower implicit categorical learning in adult poor readers.
AB  - We investigated the relationship between reading and explicit and implicit
      categorical learning by comparing university students with poor reading to
      students with normal reading abilities on two categorical learning tasks. One
      categorical learning task involved sorting simple geometric shapes into two
      groups according to a unidimensional rule. The sorting rule was easily stated by
      the participants, consistent with explicit learning, and all participants
      attained criterion levels of performance. The second task involved the
      integration of features on different dimensions with a more complex rule that
      could not be described by participants, even though most could attain criterion
      levels of performance consistent with implicit learning. Poor readers performed
      as well as those without reading problems in explicit learning but not in
      implicit learning. Implicit learning was correlated with word reading,
      phonological decoding, and orthographic skill, independent of verbal ability. We
      consider the role of implicit learning in reading, and how a deficit could impair
      phonological and orthographic representation and processing.

PMID- 15741940
TI  - Alternative approaches to the definition and identification of learning
      disabilities: some questions and answers.
AB  - Recent consensus reports concur in suggesting major changes in the federal
      regulatory approach to the identification of learning disabilities (LD). These
      reports recommend abandoning the IQ-discrepancy model and the use of IQ tests for
      identification, and also recommend incorporation of response to instruction (RTI)
      as one of the identification criteria. These changes are also recommended to
      states in the current reauthorization of the U.S. Individuals with Disabilities
      in Education Act (IDEA). While not mandatory, states that follow these
      recommendations will experience major changes in identification and treatment of
      students served under the LD category. This paper reviews the basis for these
      recommendations, summarizing four recent consensus group reports on special
      education that concur in suggesting these changes. Seventeen commonly asked
      questions about these changes are presented, with responses. In order to ensure
      adequate instruction for students with LD, it is essential that identification
      practices focus on assessments that are directly related to instruction, that any
      services for students who are struggling prioritize intervention over
      eligibility, and that special education be permitted to focus more on results and
      outcomes and less on eligibility and process. Identification models that
      incorporate RTI represent a shift in special education toward the goals of better
      achievement and behavioral outcomes for students identified with LD, as well as
      those students at risk for LD.

PMID- 15741941
TI  - Preparing novice teachers to develop basic reading and spelling skills in
      children.
AB  - This study examined the word-structure knowledge of novice teachers and the
      progress of children tutored by a subgroup of the teachers. Teachers' word
      structure knowledge was assessed using three tasks: graphophonemic segmentation,
      classification of pseudowords by syllable type, and classification of real words
      as phonetically regular or irregular. Tutored children were assessed on several
      measures of basic reading and spelling skills. Novice teachers who received word
      structure instruction outperformed a comparison group of teachers in word
      structure knowledge at post-test. Tutored children improved significantly from
      pre-test to post-test on all assessments. Teachers' post-test knowledge on the
      graphophonemic segmentation and irregular words tasks correlated significantly
      with tutored children's progress in decoding phonetically regular words; error
      analyses indicated links between teachers' patterns of word-structure knowledge
      and children's patterns of decoding progress. The study suggests that word
      structure knowledge is important to effective teaching of word decoding and
      underscores the need to include this information in teacher preparation.

PMID- 15741942
TI  - Speech recognition-based and automaticity programs to help students with severe
      reading and spelling problems.
AB  - This study was conducted to assess the effectiveness of two programs developed by
      the Frostig Center Research Department to improve the reading and spelling of
      students with learning disabilities (LD): a computer Speech Recognition-based
      Program (SRBP) and a computer and text-based Automaticity Program (AP). Twenty
      eight LD students with reading and spelling difficulties (aged 8 to 18) received
      each program for 17 weeks and were compared with 16 students in a contrast group
      who did not receive either program. After adjusting for age and IQ, both the SRBP
      and AP groups showed significant differences over the contrast group in improving
      word recognition and reading comprehension. Neither program showed significant
      differences over contrasts in spelling. The SRBP also improved the performance of
      the target group when compared with the contrast group on phonological elision
      and nonword reading efficiency tasks. The AP showed significant differences in
      all process and reading efficiency measures.

PMID- 15741943
TI  - Addressing current competitive trends.

PMID- 15741945
TI  - The pediatric rescue airway.

PMID- 15741950
TI  - Only pilots get tired and other urban myths.
AB  - Beginning in 1985, the Federal Aviation Administration (FAA) came to the
      realization that regulating crew rest for pilots was an overdue and effective
      risk-management tool. Fatigue was being increasingly recognized as a contributing
      factor in many emergency medical services (EMS) accidents. Federal aviation
      regulations were changed to include pilot crew rest and flight hour and duty time
      limitations.

PMID- 15741951
TI  - A case study in metabolic acidosis induced by inhalation.
AB  - Our program was requested to transport a 15-year-old boy weighing approximately
      100 kilograms from a clinic to a tertiary pediatric intensive care unit. The
      initial diagnosis from dispatch was for respiratory difficulties. When the flight
      crew arrived at the clinic, they were informed that the patient had been
      "huffing" carburetor cleaner for the preceding 12 hours. The patient presented to
      the clinic after 5 hours of protracted vomiting with rapid respirations.

PMID- 15741952
TI  - Permissive hypotension: a change in thinking.

PMID- 15741953
TI  - Noise-induced hearing loss.
AB  - Noise-induced hearing loss is a major hazard in many workplaces and in society.
      The National Institute for Occupational Safety and Health estimates that more
      than 30 million workers (almost 1 in 10) are exposed to unsafe noise levels on
      the job. Helicopter emergency medical services crews work in an environment in
      which exposure to aviation noise makes the issue of hearing loss and prevention
      strategies salient. Applying the Occupational Safety and Health Administration
      standard for a regulated hearing conservation program through controlling noise
      exposure will benefit helicopter emergency medical services professionals.

PMID- 15741954
TI  - Aborted air medical missions: a 4-year quality review of a Canadian province-wide
      air medical program.
AB  - INTRODUCTION: EHS LifeFlight, the air medical transport program for the province
      of Nova Scotia, is a rotor-wing program with fixed-wing backup. It flies more
      than 600 missions per year, but a varying, significant number of other requested
      missions are aborted. The purpose of this study was to examine the reasons for
      these cancellations and related pertinent descriptive data and evaluate the
      potential implications for patient care and quality service. METHODS: This study
      is a descriptive, retrospective review of all aborted missions between July 1,
      1997, and June 30, 2001. Data source was the EHS LifeFlight computer patient care
      record database. RESULTS: A total of 2723 air medical requests were received
      during the study period. Of these, 1846 were completed flight missions (68%) and
      876 were aborted missions (32%). Reasons for aborted missions included weather
      (30%), aircraft not required/not appropriate (27%), aborted by medical control
      physician (15%), aircraft out on another mission (11%), aircraft down for
      maintenance (9%), patient died before aircraft arrival (5%), no suitable landing
      zone (2%), and other (1%). CONCLUSIONS: A significant percentage of requested
      missions are aborted in this program. Reasons vary, but 20% of missions canceled
      could have been performed with the availability of a second dedicated aircraft.
      Overall, weather is the number 1 reason for aborting a mission.

PMID- 15741955
TI  - Auto launch/early activation: a survey of AAMS members and literature review.
AB  - BACKGROUND: Rapid access to definitive care is a fundamental tenet of trauma care
      and forms the basis for current emergency medical and trauma systems. Helicopters
      offer expedited transport to trauma centers and can deliver advanced practice
      personnel to the scene of injury, but many systems do not dispatch air medical
      crews until after assessment by ground providers. OBJECTIVES: Here we report data
      from the AAMS Auto Launch Survey and perform a literature review. METHODS: A 7
      question survey was developed by the AAMS Research Committee and approved by the
      board. An invitation to participate in the survey was sent by electronic mail to
      all current members. A link to an online survey was included. Results were
      presented descriptively. Some respondents were willing to share auto launch
      protocols, which were categorized into patient-related factors, event-related
      factors, and geographic considerations. RESULTS: A total of 86 usable responses
      were recorded, which represented about a third of the 240 total AAMS members. Of
      these, 38 respondents (44.2%) routinely use auto launch. Just over half of those
      using early activation reported using a combination of event- and patient-related
      considerations; most also incorporating geographic criteria. About one-third of
      respondents auto launch only at the request of ground personnel, and about one
      quarter use geographic criteria alone. Threshold distances ranged from 20 to 25
      miles or 20 to 30 minutes by ground. CONCLUSIONS: About half of respondents
      routinely use auto launch, although protocols are not consistent. Auto launch
      appears to offer a mechanism for decreasing EMS response times, but additional
      research is needed to help define optimal dispatch criteria.

PMID- 15741957
TI  - Non-invasive cardiovascular risk assessment in women with type 2 diabetes.
AB  - This study assessed and compared carotid intima-media thickness (IMT) in
      postmenopausal women with type 2 diabetes with that in postmenopausal women
      without type 2 diabetes and compared risk factors that contribute to increased
      carotid IMT in these groups of women. Carotid IMT, a non-invasive assessment of
      cardiovascular risk, was measured using high-resolution ultrasound in 20
      postmenopausal women with type 2 diabetes and 20 postmenopausal women without
      type 2 diabetes who had no known coronary heart disease. Risk factors (age, race,
      family history, diabetes, hypertension, high cholesterol, years past menopause,
      use of hormone replacement therapy, perceived level of physical activity, and
      body mass index) known to contribute to coronary heart disease were also
      assessed. Mean carotid IMT was .88 mm for women with type 2 diabetes compared
      with .74 mm for women without type 2 diabetes. There were no differences between
      groups in age, race, cholesterol, and perceived level of physical activity. Women
      with type 2 diabetes, however, reported more hypertension ( P = .004), greater
      body mass index ( P = .026), and less use of hormone replacement therapy ( P =
      .027). Of concern is that 10% of the women with diabetes had stenosis that
      required surgical intervention. Findings suggest that carotid IMT is a valid way
      to screen for cardiovascular risk, particularly in postmenopausal women who are
      at high risk for coronary heart disease. It may also be a feasible, non-invasive
      method for the detection and prevention of the macrovascular complications of
      diabetes.

PMID- 15741959
TI  - Diagnosis and management of iliac vein compression syndrome.
AB  - Iliac vein compression syndrome (IVCS) is the most probable cause of iliofemoral
      deep venous thrombosis (DVT). One half to two thirds of patients with left-sided
      iliofemoral DVT have intraluminal webs or spurs from chronic extrinsic
      compression of the left iliac vein at the crossing point of the right common
      iliac artery. Approximately 2% to 5% of those with chronic deep venous
      insufficiency of the left leg may have IVCS. IVCS occurs when compression of the
      common iliac vein is severe enough to inhibit the rate of venous outflow. In its
      more severe manifestation, IVCS is known to cause acute iliofemoral DVT. IVCS is
      caused by the combination of compression and the vibratory pressure of the right
      iliac artery on the iliac vein that is pinched between the artery and the pelvic
      bone. With the advent of catheter-directed thrombolytic therapy for patients
      presenting with iliofemoral DVT, the underlying cause has been unveiled and IVCS
      is gaining recognition. Patients presenting with symptoms of chronic venous
      insufficiency often fail conservative treatment, and because of their crippling
      symptoms, they may have a high rate of work absence or are on permanent
      disability. If IVCS can be identified as the cause and corrected, the patients'
      quality of life would improve. With the advent of endovascular stenting, the
      underlying cause can be easily corrected, and long-term patency is acceptable.
      Diagnosis can be made by being highly suspicious when patients present in either
      the acute or chronic state and selecting the best diagnostic tool to confirm the
      diagnosis. This article discusses the prevalence of IVCS, its significance for
      the affected population, and the relevance of recognition, and reviews the best
      methods of its diagnosis and treatment. Special emphasis is placed on diagnostic
      tools and their efficacy, and our results to date are reported.

PMID- 15741961
TI  - Vascular risk management through nurse-led self-management programs.
AB  - In current clinical practice, adequate cardiovascular risk reduction is difficult
      to achieve. Treatment is primarily focused on clinical vascular disease and not
      on long-term risk reduction. Pertinent to success in vascular risk reduction are
      proper medication use, weight control, healthy food choices, smoking cessation,
      and physical exercise. Atherosclerotic vascular disease and its risk constitute a
      chronic condition, which poses specific requirements on affected patients and
      caregivers who should be aware of the chronicity. In patients with vascular
      disease, there is lack of awareness of their chronic condition because of the
      invisibility of most risk factors. In other patient groups with chronic illness,
      self-management programs were successful in achieving behavioral change. This
      strategy can also be useful for patients with vascular disease to adapt and
      adhere to an improved lifestyle. Self-management refers to the individual's
      ability to manage both physical and psychosocial consequences including lifestyle
      changes inherent to living with a chronic condition. Interventions that promote
      self-management are based on enhancing self-efficacy. In self-management,
      attention can be given to what is important and motivational to the individual
      patient. In this article the challenge of nursing care promoting self-management
      for patients with vascular risk and how this care can be applied will be
      explained. Nurses can play a central role in vascular risk management with a self
      management approach for patients with chronic vascular disease. In vascular
      prevention clinics, nursing care can be delivered that includes medical treatment
      of vascular risks (hypertension, hypercholesterolemia, hyperglycemia, and
      hyperhomocystinemia) and counseling on promoting self-management (changes in
      diet, body weight, smoking habits, and level of exercise). Nursing interventions
      based on self-management promotion can provide a new and promising approach to
      actually achieve vascular risk reduction.

PMID- 15741963
TI  - In pursuit of magnet status: the impact of nursing research.

PMID- 15741962
TI  - Understanding discharge instructions after vascular surgery: an observational
      study.
AB  - Patient education is a dynamic ongoing process that occurs from admission to
      discharge. Vascular surgery is an intensive procedure that causes stress to
      patient and family members. High stress levels in patients are a barrier to
      learning. There is a large body of knowledge available on patient education.
      However, research is lacking on patient retention of discharge instructions after
      vascular surgery. This study describes patient responses to 4 questions that were
      asked 3 days after in-hospital teaching was completed by a registered nurse
      regarding either femoral-popliteal bypass surgery or abdominal aortic aneurysm
      repair surgery.

PMID- 15741964
TI  - Vascular nurse competency in aging.

PMID- 15741965
TI  - Venous disorders: overview of current practice.
AB  - Venous disease often is overlooked until the problems it causes become severe.
      When patients present with concomitant diseases or disorders, those disorders may
      take priority both in the patient's mind and the caregiver's. Fortunately, there
      has been an increasing interest in the diagnoses and treatment of venous
      disorders and with this is a renewed interest in early diagnosis of venous
      problems and identification of individuals at risk for venous problems.

PMID- 15741967
TI  - A new global strategy for the life sciences in Europe.

PMID- 15741968
TI  - Curing ageing and the consequences. An interview with Aubrey de Grey, biomedical
      gerontologist at the University of Cambridge, UK. Interview by Holger Breithaupt
      and Caroline Hadley.

PMID- 15741969
TI  - Drug safety on trial. Last year's withdrawal of the anti-arthritis drug Vioxx
      triggered a debate about how to better monitor drug safety even after approval.

PMID- 15741970
TI  - Short-circuiting our fossil fuel habits. Could a more direct harnessing of
      photosynthesis become an alternative to natural oil, coal and gas?

PMID- 15741971
TI  - Laptop biology. As mathematics and computation increasingly invade laboratories,
      biologists need to master new skills.

PMID- 15741974
TI  - Actin in transcription. Actin is required for transcription by all three RNA
      polymerases in the eukaryotic cell nucleus.

PMID- 15741975
TI  - The state of the filament.
AB  - Movement is a defining characteristic of life. Macroscopic motion is driven by
      the dynamic interactions of myosin with actin filaments in muscle. Directed
      polymerization of actin behind the advancing membrane of a eukaryotic cell
      generates microscopic movement. Despite the fundamental importance of actin in
      these processes, the structure of the actin filament remains unknown. The Holmes
      model of the actin filament was published 15 years ago, and although it has been
      widely accepted, no high-resolution structural data have yet confirmed its
      veracity. Here, we review the implications of recently determined structures of F
      actin-binding proteins for the structure of the actin filament and suggest a
      series of in silico tests for actin-filament models. We also review the
      significance of these structures for the arp2/3-mediated branched filament.

PMID- 15741977
TI  - Extravasation of the contrast media during voiding cystourethrography in a long
      term spinal cord injury patient.
AB  - OBJECTIVE: To present complications and pitfalls in voiding cystourethrography
      (VCUG) and introduce a guideline for performing VCUG in a long-term spinal cord
      injury (SCI) patient with neurogenic bladder dysfunction (NBD) and contracted
      bladder. STUDY DESIGN: A case report. SETTING: Maharaj Nakorn Chiang Mai
      Hospital, Chiang Mai, Thailand. METHOD: We describe a chronic C(5) tetraplegic
      man with NBD and contracted bladder, who developed autonomic dysreflexia (AD),
      gross hematuria and extravasation of contrast median during VCUG. RESULT: A foley
      catheter was retained after VCUG. AD was resolved and urine cleared after a week
      of continuous bladder irrigation. CONCLUSION: VCUG should be performed with
      caution in a long-term SCI patient with NBD and contracted bladder. Forceful
      pushing of the contrast media by the hand-injection method caused abrupt
      distention of the contracted bladder, damaged bladder mucosa and aggrevated AD.
      We suggest a guideline as follows: report bladder capacity and AD, if present, in
      an X-ray requisition form; use the gravity-drip method, stop the drip and drain
      the contrast media if a sudden headache and rising of blood pressure (BP)
      develop; observe urine colour, and report if bleeding or AD occurs.

PMID- 15741978
TI  - Adverse events after botulinum A toxin injection for neurogenic voiding
      disorders.
AB  - OBJECTIVES: To review the side effects of local injections of botulinum A toxin
      (BTX-A). METHODS: A medline search for publications about adverse events after
      injection of BTX-A for lower urinary tract dysfunctions. RESULTS: We found four
      publications that report generalised side effects after BTX-A injection for
      detrusor overactivity (two) and detrusor-sphincter dyssynergia (two). The causes
      of generalised adverse events are not clear, but spread outside the target organ
      and into the systemic circulation may contribute. The dose used, the injection
      volume and the injection technique can all play a role. CONCLUSION: Generalised
      side effects after BTX-A injection for voiding disorders are rare but they can be
      very disabling for spinal cord-injured patients. Although no long-term side
      effects are reported so far, urologists should be aware that these effects of BTX
      A injections are unknown.

PMID- 15741979
TI  - Breathing and the support of blood pressure after spinal cord injury.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: The recognized effect of breathing
      on venous return and cardiac output has not been assessed in the spinal cord
      injury (SCI) patient. To test this effect indirectly, the breathing capacity and
      blood pressure have been compared at various levels of SCI. SETTING: SCI service,
      Massachusetts, USA. METHODS: Spinal cord-injured subjects with complete motor
      paralysis were studied. The forced vital capacity (FVC) (one study, 455 subjects,
      91% male) was compared with the mean blood pressure (MBP) (one study, 461
      subjects, 100% male) of subjects by level of paralysis. RESULTS: For lumbar to
      cervical levels of paralysis, FVC and MBP each diminish progressively. To compare
      FVC directly with MBP by level of paralysis, r=0.85, P<0.001. CONCLUSION:
      Breathing capacity is correlated with blood pressure in SCI patients.

PMID- 15741980
TI  - Rehabilitation of spinal cord injury in France: a nationwide multicentre study of
      incidence and regional disparities.
AB  - STUDY DESIGN: Multicentre retrospective 1-year survey during 2000. OBJECTIVES: To
      describe the network of physical medicine and rehabilitation units in France that
      care for people with traumatic spinal cord injuries (SCI), and secondly, to
      evaluate the incidence of SCI persons who have postinjury rehabilitation care.
      SETTING: Every rehabilitation unit involved in rehabilitation of SCI patients in
      metropolitan France. METHODS: During the first phase of the survey, a
      questionnaire was used to list the rehabilitation units that treat SCI people
      among a total of 380 centres. An additional survey was then carried out on a
      sample of 30 units that did not answer this questionnaire. In the second phase,
      the units involved were asked about the number of SCI patients received for a
      first rehabilitation stay during the year 2000 and their demographic and clinical
      characteristics. The incidence was calculated on the basis of the population
      census in metropolitan France aged 15 years, above. RESULTS: Of the 275
      respondent units, 148 declared that they treat SCI people on a regular or
      occasional basis. The survey on the sample of 30 randomly selected nonrespondents
      enabled us to estimate that 10% of the 105 nonrespondent units were concerned.
      Among the 148 units contributing to the study, 131 identified all the SCI
      patients received during the year 2000. After a series of adjustments, an
      extrapolation for all of metropolitan France leads to an annual incidence of 19.4
      SCI persons per million inhabitants, or 934 new cases per year. CONCLUSION: This
      is the first nationwide survey aiming to estimate the incidence of SCI patients
      in France. The finding is based on the incidence of SCI persons treated in
      rehabilitation units. It therefore concerns the incidence of patients who will
      remain severely disabled.

PMID- 15741981
TI  - Cervical fracture and cervical cord injury during anger management course.

PMID- 15741982
TI  - Analysis of nutritional parameters in idiopathic scoliosis patients after major
      spinal surgery.
AB  - OBJECTIVE: The aim of the study is to investigate the evolution of nutritional
      parameters after major spinal surgery in patients with idiopathic scoliosis.
      METHODS: This retrospective study included 31 patients with a mean age of 18 y,
      diagnosed with idiopathic scoliosis. The following variables were analyzed:
      demographic, surgical (type, number of fused segments, duration, and blood loss),
      nutritional assessment (proteins, albumin, prealbumin, transferrin, lymphocytes,
      and body mass index), and duration of hospitalization at different time points.
      Statistical analyses were performed with the SPSS 6.1 software. RESULTS: Before
      surgery, nutritional status was normal in all patients. At 24-48 h after surgery,
      statistically significant decrease with respect to preoperative values was
      recorded for all the parameters studied: proteins (P < 0.001), albumin (P <
      0.001), prealbumin (P < 0.01), transferrin (P < 0.001), and lymphocytes (P <
      0.001). CONCLUSION: Our results showed a significant postoperative decrease in
      the nutritional parameters analyzed in a previously well-nourished population
      considered to be at low risk for nutritional depletion.

PMID- 15741983
TI  - Young adolescents' nutrition assessment on computer (YANA-C).
AB  - OBJECTIVE: To assess the relative validity and acceptability of the computerised
      24-h recall 'Young Adolescent's Nutrition Assessment on Computer (YANA-C)'.
      DESIGN: Food and nutrient intakes assessed with YANA-C were compared with food
      records (study 1) and 24-h dietary recall interviews (study 2). MAIN OUTCOME
      MEASURES: Intakes of food groups (fruit, fruit juice, vegetables, potatoes,
      bread, cereals, milk, cheese, other milk products, soft drinks, diet soft drinks,
      sugar/sweets, pastry/cookies, savoury snacks, butter/sauces, eggs, fish, meat)
      and nutrients (energy, carbohydrates, protein, fat, fiber, calcium, vitamin C and
      iron). SUBJECTS AND SETTING: A total of 237 pupils (11-14 y) from two primary and
      four secondary schools (study 1: n = 136; study 2: n = 101) in Belgium-Flanders.
      RESULTS: YANA-C proved to agree well with both standard methods in categorizing
      subjects in consumers and nonconsumers (kappa(study 1) = 0.48-0.92; kappa(study
      2) = 0.38-0.90). Spearman's correlations for energy and nutrient intakes ranged
      between 0.44 and 0.79 for study 1 and between 0.44 and 0.86 for study 2. Nutrient
      and energy intakes were in general (excluding calcium) significantly higher in
      YANA-C in comparison with the food record, but not in comparison with the
      interview (only fiber). Statistics used to investigate whether YANA-C agreed with
      the other methods in ranking portions/amounts in consumers only were fair to
      moderate for most of the food groups (weighted kappa study 1 = 0.11-0.55; study 2
      = 0.04-0.73); amounts in consumers only, were significantly lower in YANA-C
      against both standards for cereals; amounts were significantly higher in YANA-C
      against the food record for milk, soft drinks, sugar/sweets and savoury snacks
      and against the interview for potatoes. Only a few pupils evaluated the program
      negatively. CONCLUSION: YANA-C is a promising method to collect detailed dietary
      information from young adolescents with relatively low staff resources, useful in
      many nutrition research applications.

PMID- 15741984
TI  - A real epidemiological study?

PMID- 15741985
TI  - Low plasma selenium concentrations, high plasma human immunodeficiency virus load
      and high interleukin-6 concentrations are risk factors associated with anemia in
      adults presenting with pulmonary tuberculosis in Zomba district, Malawi.
AB  - BACKGROUND: Although anemia is common among adults with pulmonary tuberculosis
      and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the
      factors contributing to its pathogenesis have not been well characterized.
      OBJECTIVE: To characterize the antioxidant micronutrient status, interleukin-6
      (IL-6) concentrations, and HIV load in relationship with anemia in adults with
      pulmonary tuberculosis. SETTING: Zomba district, Malawi. METHODS: Erythropoietin,
      IL-6, plasma HIV load, and markers of micronutrient status (hemoglobin (Hb),
      plasma concentrations of retinol, alpha-tocopherol, carotenoids, ferritin, zinc,
      and selenium) were measured in 500 adults who presented with pulmonary
      tuberculosis in Zomba Central Hospital, Malawi. RESULTS: Among 370 HIV-positive
      and 130 HIV-negative adults, the prevalence of anemia was 88 and 77%,
      respectively (P = 0.002), and moderate to severe anemia (Hb < 80 g/l) occurred in
      30 and 15%, respectively (P = 0.001). Geometric mean IL-6 concentration was 21.1
      pg/ml, with no difference between HIV-positive and -negative adults. The
      erythropoietin response to anemia was not different between adults with elevated
      IL-6 and those with lower IL-6 concentrations. In a multivariate logistic
      regression model, HIV load, and lower plasma selenium concentrations were
      associated with moderate to severe anemia. In a final multivariate linear
      regression model, IL-6, plasma HIV load, and plasma selenium concentrations were
      associated with Hb concentrations. CONCLUSION: This study suggests that low
      selenium concentrations, high HIV load, and high IL-6 concentrations are
      associated with anemia in adults with pulmonary tuberculosis in sub-Saharan
      Africa.

PMID- 15741986
TI  - Clinical accuracy of the MedGem indirect calorimeter for measuring resting energy
      expenditure in cancer patients.
AB  - OBJECTIVE: To compare, in patients with cancer and in healthy subjects, measured
      resting energy expenditure (REE) from traditional indirect calorimetry to a new
      portable device (MedGem) and predicted REE. DESIGN: Cross-sectional clinical
      validation study. SETTING: Private radiation oncology centre, Brisbane,
      Australia. SUBJECTS: Cancer patients (n = 18) and healthy subjects (n = 17) aged
      37-86 y, with body mass indices ranging from 18 to 42 kg/m(2). INTERVENTIONS:
      Oxygen consumption (VO(2)) and REE were measured by VMax229 (VM) and MedGem (MG)
      indirect calorimeters in random order after a 12-h fast and 30-min rest. REE was
      also calculated from the MG without adjustment for nitrogen excretion (MGN) and
      estimated from Harris-Benedict prediction equations. Data were analysed using the
      Bland and Altman approach, based on a clinically acceptable difference between
      methods of 5%. RESULTS: The mean bias (MGN-VM) was 10% and limits of agreement
      were -42 to 21% for cancer patients; mean bias -5% with limits of -45 to 35% for
      healthy subjects. Less than half of the cancer patients (n = 7, 46.7%) and only a
      third (n = 5, 33.3%) of healthy subjects had measured REE by MGN within
      clinically acceptable limits of VM. Predicted REE showed a mean bias (HB-VM) of 
      5% for cancer patients and 4% for healthy subjects, with limits of agreement of 
      30 to 20% and -27 to 34%, respectively. CONCLUSIONS: Limits of agreement for the
      MG and Harris Benedict equations compared to traditional indirect calorimetry
      were similar but wide, indicating poor clinical accuracy for determining the REE
      of individual cancer patients and healthy subjects.

PMID- 15741987
TI  - Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy
      Italian population: the 'Florence' diet is not Mediterranean.
AB  - OBJECTIVE: To evaluate dietary habits and lifestyle of Italian subjects, to
      provide current data on adequacy of the nutritional guidelines and
      recommendations especially in relation to primary prevention of cardiovascular
      diseases and to assess the influence of dietary habits on lipid profile and
      homocysteine levels. DESIGN: Cross-sectional. SETTING: Population-based study.
      SUBJECTS: A sample of 520 clinically healthy subjects (211 males, 309 females)
      with a mean age of 46 y, living in Florence area, Italy. INTERVENTIONS: Dietary
      pattern was assessed by trained dietitians through a semiquantitative food
      questionnaire. Fasting blood samples were drawn for assessment of lipid profile,
      homocysteine and circulating vitamins. RESULTS: Contribution from total fats was
      over 30% in about 70% of subjects and intake of saturated fatty acids (SFA) was
      above the recommended values in at least 40% of the study population.
      Furthermore, almost the whole (99.6%) population reported low intake of
      polyunsaturated fatty acids (PUFA). High levels of total cholesterol were present
      in over 40% of the study population, whereas abnormal values of LDL-cholesterol
      were observed in about 30%. High levels of homocysteine were found in 11.7% of
      the study population. An extremely high percentage of subjects reported low
      intake of vitamins, especially with regard to folic acid (89%), vitamin B(6)
      (70.1%) and vitamin E (99.6%). In a multiple linear regression model, circulating
      levels of vitamin B(12) and folic acid, and intake of alcohol and vitamin C
      resulted in being independently associated with homocysteine plasma levels.
      CONCLUSIONS: In a typical Mediterranean country, general outlines of
      Mediterranean diet are not completely followed, especially concerning total fats,
      SFA, PUFA and vitamins' intake. SPONSORSHIP: Ministero della Salute (Italy) -
      'Progetto per la Salute e la Prevenzione di Malattia' 2001-2003.

PMID- 15741988
TI  - Modulation of COX-2 expression in peripheral blood cells by increased intake of
      fruit and vegetables?
AB  - BACKGROUND: Enhanced cyclooxygenase-2 (COX-2) expression is associated with
      carcinogenesis, ischemia, angiogenesis, inflammation, and neurodegeneration. The
      preventing effect of aspirin and nonsteroidal anti-inflammatory drugs is partly
      due to inhibition of the COX-2 enzyme. Fruit and vegetables (FVs) contain
      numerous compounds that may decrease disease risk by several different
      mechanisms, for example through the inhibition of COX-2 activity. OBJECTIVE: We
      tested the hypothesis that an increased intake of FVs would modulate the COX-2
      expression in peripheral blood cells. DESIGN: A strictly controlled dietary
      crossover study (n = 39). After 1 week run-in period with no FVs in the diet, one
      group was given two portions of FVs (2 FV), while another group was given five
      portions (5 FV) daily for 14 days. Following a 2 weeks washout period and 1 week
      run-in, the regimens were switched between the groups. Gene expression analysis
      of COX-2 mRNA in blood samples was performed by quantitative real-time-PCR.
      RESULTS: No significant treatment effect of diet intervention was found in the
      crossover analyses (P = 0.74). However, the individual variation in response may
      seem large. CONCLUSIONS: These data does not contradict the recommendations for
      an increased intake of FVs. Further studies on expression directly and
      indirectly, through analysis of factors regulating and being regulated by COX-2,
      should be carried out. A first step would be to evaluate the correspondence
      between COX-2 mRNA expression and products of the COX pathway, like
      prostaglandins. Naturally occurring polymorphisms of COX-2 promoters and coding
      regions might contribute to functional variations and response to different
      diets. SPONSORSHIP: Norwegian Research Council, National Nutrition Council,
      Throne Holst Foundation for Nutrition Research, Freia Chokoladefabriks Medisinske
      Fond and the Norwegian Cancer Society.

PMID- 15741989
TI  - Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with
      type II diabetes mellitus.
AB  - OBJECTIVE: We designed this study to investigate the effects of oral L-carnitine
      administration on fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c)
      and lipid parameters in patients with diabetes mellitus type II. PATIENTS AND
      METHODS: The effect of L-carnitine on FPG and lipid parameters was investigated
      in 22 male and 13 female type II diabetic patients; the mean age +/- s.d. was
      51.3 +/- 3.7 y. The patients were randomly allocated to two groups (L-carnitine
      and placebo group) and 1 g of L-carnitine or of placebo was given orally three
      times a day for a period of 12 weeks. RESULTS: FPG in the L-carnitine group
      decreased significantly from 143 +/- 35 to 130 +/- 33 mg/dl (P = 0.03), and we
      observed a significant increase of triglycerides (TG) from 196+/-61 to 233+/-12
      mg/dl (P = 0.05), of Apo A1 from 94 +/- 20 to 103 +/- 23 mg/dl (P = 0.02), and of
      Apo B100 from 98 +/- 18 to 108 +/- 22 mg/dl (P = 0.02) after 12 weeks of
      treatment. There was no significant change in LDL-C, HDL-C, HbA1C, LP(a) or total
      cholesterol. CONCLUSION: L-Carnitine significantly lowers FPG but increases
      fasting triglyceride in type II diabetic patients.

PMID- 15741990
TI  - Genetic epidemiology of cancer: relatively risky relatives.

PMID- 15741992
TI  - Frequency of large CFTR gene rearrangements in Italian CF patients.
AB  - In most populations, an appreciable fraction of cystic fibrosis transmembrane
      regulator (CFTR) gene mutations in patients affected by cystic fibrosis (CF)
      cannot be identified, and large gene rearrangements might be missed by standard
      analyses. We have searched large gene rearrangements in a sample of 25 North East
      Italian CF patients who, after an extensive gene analysis of 188 patients, still
      bear one or two unidentified CF mutations. A systematic gene screening by
      quantitative multiplex PCR of short fluorescent fragments was performed. Overall,
      5/26 (19.2%) rearranged alleles were detected, bearing mutation 3120+1Kbdel8.6Kb
      (three patients), and c.4_IVS1+69del119bpins299bp (two patients). These mutations
      were observed in compound heterozygotes with F508del or termination mutations,
      and a pancreatic insufficient form of CF. These findings confirm the frequency of
      CFTR gene rearrangements recently observed in French CF patients.

PMID- 15741991
TI  - Differential epigenetic modifications in the FMR1 gene of the fragile X syndrome
      after reactivating pharmacological treatments.
AB  - The fragile X syndrome is caused by a >200 CGG repeat expansion within the FMR1
      gene promoter, with consequent DNA hypermethylation and inactivation of its
      expression. To further clarify the mechanisms that suppress the activity of the
      mutant gene and the conditions that may permit its reactivation, we investigated
      the acetylation and methylation status of three different regions of the FMR1
      gene (promoter, exon 1 and exon 16) of three fragile X cell lines, using a
      chromatin immunoprecipitation (ChIP) assay with antibodies against acetylated
      H3/H4 histones and against dimethylated lysine residues K4 and K9 of histone H3
      (H3-K4 and H3-K9). We then coupled the ChIP assay with real-time PCR, obtaining
      absolute quantification of immunoprecipitated chromatin. Basal levels of histone
      acetylation and H3-K4 methylation were much higher in transcriptionally active
      wild-type controls than in inactive fragile X cell lines. Treatment of fragile X
      cell lines with the DNA demethylating drug 5-aza-2-deoxycytidine (5-azadC), known
      to reactivate the FMR1 gene, induced a decrease of H3-K9 methylation, an increase
      of H3 and H4 acetylation and an increase of H3-K4 methylation. Treatment with
      acetyl-L-carnitine (ALC), a compound that reduces the in vitro expression of the
      FRAXA fragile site without affecting DNA methylation, caused an increase of H3
      and H4 acetylation. However, H3-K4 methylation remained extremely low, in
      accordance with the observation that ALC alone does not reactivate the FMR1 gene.
      Our experiments indicate that H3-K4 methylation and DNA demethylation are the
      main epigenetic switches activating the expression of the FMR1 gene, with histone
      acetylation playing an ancillary role.

PMID- 15741993
TI  - Familial nonrandom inactivation linked to the X inactivation centre in
      heterozygotes manifesting haemophilia A.
AB  - A basic tenet of the Lyon hypothesis is that X inactivation occurs randomly with
      respect to parental origin of the X chromosome. Yet, nonrandom patterns of X
      inactivation are common - often ascertained in women who manifest recessive X
      linked disorders despite being heterozygous for the mutation. Usually, the cause
      of skewing is cell selection disfavouring one of the cell lineages created by
      random X inactivation. We have identified a three generation kindred, with three
      females who have haemophilia A because of extreme skewing of X inactivation.
      Although they have both normal and mutant factor VIII (FVIII) alleles, only the
      mutant one is transcribed; and, they share an XIST allele that is never
      transcribed. The skewing in this case seems to result from an abnormality in the
      initial choice process, which prevents the chromosome bearing the mutant FVIII
      allele from being an inactive X.

PMID- 15741994
TI  - Functional disomy of the Xq28 chromosome region.
AB  - We report on two patients, a boy and a girl, with an additional Xq28 chromosome
      segment translocated onto the long arm of an autosome. The karyotypes were
      46,XY,der(10)t(X;10)(q28;qter) and 46,XX,der(4)t(X;4)(q28;q34), respectively. In
      both cases, the de novo cryptic unbalanced X-autosome translocation resulted in a
      Xq28 chromosome functional disomy. To our knowledge, at least 17 patients with a
      distal Xq chromosome functional disomy have been described in the literature.
      This is the third report of a girl with an unbalanced translocation yielding such
      a disomy. When the clinical features of both patients are compared to those
      observed in patients reported in the literature, a distinct phenotype emerges
      including severe mental retardation, facial dysmorphic features with a wide face,
      a small mouth and a thin pointed nose, major axial hypotonia, severe feeding
      problems and proneness to infections. A clinically oriented FISH study using
      subtelomeric probes is necessary to detect such a cryptic rearrangement.

PMID- 15741995
TI  - Unclassified variants in disease-causing genes: nonuniformity of genetic testing
      and counselling, a proposal for guidelines.

PMID- 15741996
TI  - Mutations and sequence variation in the human myosin heavy chain IIa gene (MYH2).
AB  - We recently described a new autosomal dominant myopathy associated with a
      missense mutation in the myosin heavy chain (MyHC) IIa gene (MYH2). In this
      study, we performed mutation analysis of MYH2 in eight Swedish patients with
      familial myopathy of unknown cause. In two of the eight index cases, we
      identified novel heterozygous missense mutations in MYH2, one in each case: V970I
      and L1061V. The mutations were located in subfragment 2 of the MyHC and they
      changed highly conserved residues. Most family members carrying the mutations had
      signs and symptoms consisting mainly of mild muscle weakness and myalgia. In
      addition, we analyzed the extent and distribution of nucleotide variation in MYH2
      in 50 blood donors, who served as controls, by the complete sequencing of all 38
      exons comprising the coding region. We identified only six polymorphic sites,
      five of which were synonymous polymorphisms. One variant, which occurred at an
      allele frequency of 0.01, was identical to the L1061V that was also found in one
      of the families with myopathy. The results of the analysis of normal variation
      indicate that there is strong selective pressure against mutations in MYH2. On
      the basis of these results, we suggest that MyHC genes should be regarded as
      candidate genes in cases of hereditary myopathies of unknown etiology.

PMID- 15741997
TI  - A single locus determines thelytokous parthenogenesis of laying honeybee workers
      (Apis mellifera capensis).
AB  - The evolution and maintenance of parthenogenetic species are a puzzling issue in
      evolutionary biology. Although the genetic mechanisms that act to restore
      diploidy are well studied, the underlying genes that cause the switch from sexual
      reproduction to parthenogenesis have not been analysed. There are several species
      that are polymorphic for sexual and parthenogenetic reproduction, which may have
      a genetic basis. We use the South African honeybee subspecies Apis mellifera
      capensis to analyse the genetic control of thelytoky (asexual production of
      female workers). Due to the caste system of honeybees, it is possible to
      establish classical backcrosses using sexually reproducing queens and drones of
      both arrhenotokous and thelytokous subspecies, and to score the frequency of
      parthenogenesis in the resulting workers. We found Mendelian segregation for
      thelytoky of egg-laying workers, which appears to be controlled by a single major
      gene (th). The segregation pattern indicates a recessive allele causing
      thelytoky. We found no evidence for maternal transmission of bacterial
      endosymbionts controlling parthenogenesis. Thelytokous parthenogenesis of
      honeybee workers appears to be a classical qualitative trait, because we did not
      observe mixed parthenogenesis (amphitoky), which might be expected in the case of
      multi-locus inheritance.

PMID- 15741998
TI  - Impact of clonal growth on effective population size in Hymenoxys herbacea
      (Asteraceae).
AB  - By influencing the proliferation of different genotypes, clonal growth can affect
      the maintenance of genetic variability and magnitude of genetic drift within
      plant populations. However, estimates of effective population size rarely
      incorporate the contribution of both asexual and sexual reproduction. We
      estimated effective size (Ne) for two populations of the clonal, self
      incompatible plant, Hymenoxys herbacea, using a stage-structured demographic
      model for organisms with asexual and sexual recruitment and then examined the
      impact of reproductive strategy using an elasticity analysis. Plant rosettes
      monitored in two successive years had high survival rates in both populations
      (mean 0.94). The mean number of sexually derived recruits per initial ramet was
      0.041 (SE 0.039), whereas the mean number of clonal recruits was 0.61 (SE 0.90).
      Effective size was 1642 and 5769 in the two populations and the Ne/N ratio
      averaged 0.34, comparable to values for other clonal species. Elasticity analysis
      indicated that increases in both clonal and sexual recruitment cause an increase
      in Ne while increasing the variance reduced Ne. However, Ne was more sensitive to
      changes in the mean and variance of asexual recruitment than sexual recruitment.
      These results highlight the importance of considering asexual modes of
      reproduction when examining the role of genetic stochasticity in populations.

PMID- 15741999
TI  - Molecular and quantitative genetic divergence among populations of house mice
      with known evolutionary histories.
AB  - Evolutionary biologists have long been interested in the processes influencing
      population differentiation, but separating the effects of neutral and adaptive
      evolution has been an obstacle for studies of population subdivision. A recently
      developed method allows tests of whether disruptive (ie, spatially variable) or
      stabilizing (ie, spatially uniform) selection is influencing phenotypic
      differentiation among subpopulations. This method, referred to as the F(ST) vs
      Q(ST) comparison, separates the total additive genetic variance into within- and
      among-population components and evaluates this level of differentiation against a
      neutral hypothesis. Thus, levels of neutral molecular (F(ST)) and quantitative
      genetic (Q(ST)) divergence are compared to evaluate the effects of selection and
      genetic drift on phenotypic differentiation. Although the utility of such
      comparisons appears great, its accuracy has not yet been evaluated in populations
      with known evolutionary histories. In this study, F(ST) vs Q(ST) comparisons were
      evaluated using laboratory populations of house mice with known evolutionary
      histories. In this model system, the F(ST) vs Q(ST) comparisons between the
      selection groups should reveal quantitative trait differentiation consistent with
      disruptive selection, while the F(ST) vs Q(ST) comparisons among lines within the
      selection groups should suggest quantitative trait differentiation in agreement
      with drift. We find that F(ST) vs Q(ST) comparisons generally produce the correct
      evolutionary inference at each level in the population hierarchy. Additionally,
      we demonstrate that when strong selection is applied between populations Q(ST)
      increases relative to Q(ST) among populations diverging by drift. Finally, we
      show that the statistical properties of Q(ST), a variance component ratio, need
      further investigation.

PMID- 15742000
TI  - Effect of inbreeding and heritability of sperm competition success in the bulb
      mite Rhizoglyphus robini.
AB  - Sperm competition is a potent evolutionary force shaping the reproductive biology
      of most animal species. Here, we estimated the heritability of sperm competition
      success in the promiscuous bulb mite Rhizoglyphus robini. Sperm competition
      success was measured with the sterile male technique as the proportion of eggs
      fertilised by the second of three males mated with a single female. Sperm
      competition success responded significantly to selection. The heritability
      estimated from the response to five generations of selection was 0.13. We also
      estimated the effect of inbreeding on sperm competition success. Males produced
      by sib-mating (F=0.25) had a significantly lower sperm competition success than
      outbred males. The estimated coefficient of inbreeding depression was 0.53. Such
      high inbreeding depression together with moderately low heritability is
      consistent with the view that sperm competitive ability is under strong
      directional selection and strongly influences the reproductive success of males.

PMID- 15742001
TI  - What ancient DNA tells us.

PMID- 15742002
TI  - Disequilibrium in some Cepaea populations.
AB  - Phenotypic disequilibrium is a measure available, along with morph frequency, in
      many published sets of sample data recording the polymorphism of shell colour and
      pattern in the snail Cepaea nemoralis. The relation of disequilibrium to morph
      frequency for the colour (pink/yellow) and banding (unbanded/banded) loci has
      been examined for a large and widespread set of data. The direction of
      disequilibrium is a function of frequency at the two loci in a way that suggests
      that selection favours combinations of common morphs, whichever they are. This
      could indicate that such combinations are common because they have been selected.
      The data are therefore consistent with the proposal that populations are
      generally subject to selection of varying directions at different places and
      times, acting on the phenotype. In combination with migration, such selection
      could lead to prolonged polymorphism.

PMID- 15742003
TI  - Local genetic population structure in an endangered plant species, Silene
      tatarica (Caryophyllaceae).
AB  - Genetic substructuring in plant populations may evolve as a consequence of
      sampling events that occur when the population is founded or regenerated, or if
      gene dispersal by pollen and seeds is restricted within a population. Silene
      tatarica is an endangered, perennial plant species growing along periodically
      disturbed riverbanks in northern Finland. We investigated the mechanism behind
      the microspatial genetic structure of S. tatarica in four subpopulations using
      amplified fragment length polymorphism markers. Spatial autocorrelation revealed
      clear spatial genetic structure in each subpopulation, even though the pattern
      diminished in older subpopulations. Parentage analysis in an isolated island
      subpopulation indicated a very low level of selfing and avoidance of breeding
      between close relatives. The mean estimated pollen dispersal distance (24.10 m;
      SD = 10.5) was significantly longer and the mean seed dispersal distance (9.07 m;
      SD = 9.23) was considerably shorter than the mean distance between the
      individuals (19.20 m; SD = 13.80). The estimated indirect and direct estimates of
      neighbourhood sizes in this subpopulation were very similar, 32.1 and 37.6,
      respectively. Our results suggested that the local spatial genetic structure in
      S. tatarica was attributed merely to the isolation-by-distance process rather
      than founder effect, and despite free pollen movement across population,
      restricted seed dispersal maintains local genetic structure in this species.

PMID- 15742004
TI  - Lack of CB1 cannabinoid receptor impairs cocaine self-administration.
AB  - Acute rewarding properties are essential for the establishment of cocaine
      addiction, and multiple neurochemical processes participate in this complex
      behavior. In the present study, we used the self-administration paradigm to
      evaluate the role of CB1 cannabinoid receptors in several aspects of cocaine
      reward, including acquisition, maintenance, and motivation to seek the drug. For
      this purpose, both CB1 receptor knockout mice and wild-type littermates were
      trained to intravenously self-administer cocaine under different schedules.
      Several cocaine training doses (0.32, 1, and 3.2 mg/kg/infusion) were used in the
      acquisition studies. Only 25% of CB1 knockout mice vs 75% of their wild-type
      littermates acquired a reliable operant responding to self-administer the most
      effective dose of cocaine (1 mg/kg/infusion), and the number of sessions required
      to attain this behavior was increased in knockout mice. Animals reaching the
      acquisition criteria were evaluated for the motivational strength of cocaine as a
      reinforcer under a progressive ratio schedule. The maximal effort to obtain a
      cocaine infusion was significantly reduced after the genetic ablation of CB1
      receptors. A similar result was obtained after the pharmacological blockade of
      CB1 receptors with SR141716A in wild-type mice. Moreover, the cocaine dose
      response curve was flattened in the knockout group, suggesting that the
      differences observed between genotypes were related to changes in the reinforcing
      efficacy of the training dose of cocaine. Self-administration for water and food
      was not altered in CB1 knockout mice in any of the reinforcement schedules used,
      which emphasizes the selective impairment of drug reinforcement in these knockout
      mice. Finally, cocaine effects on mesolimbic dopaminergic transmission were
      evaluated by in vivo microdialysis in these mice. Acute cocaine administration
      induced a similar enhancement in the extracellular levels of dopamine in the
      nucleus accumbens of both CB1 knockout and wild-type mice. This work clearly
      demonstrates that CB1 receptors play an important role in the consolidation of
      cocaine reinforcement, although are not required for its acute effects on
      mesolimbic dopaminergic transmission.

PMID- 15742005
TI  - A randomized, double-blind, study of rofecoxib in patients with mild cognitive
      impairment.
AB  - Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and
      might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2
      inhibitors, rofecoxib and celecoxib, have shown that they do not alter the
      progression of AD. We conducted a double-blind study to investigate whether
      rofecoxib could delay a diagnosis of AD in patients with mild cognitive
      impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%.
      MCI patients > or =65 years were randomized to rofecoxib 25 mg (N=725) or placebo
      (N=732) daily for up to 4 years. The primary end point was the percentage of
      patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate
      was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the
      placebo group (rofecoxib : placebo hazard ratio=1.46 (95% CI: 1.09, 1.94),
      p=0.011). Analyses of secondary end points, including measures of cognition (eg
      the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function
      (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between
      treatment groups. There was also no consistent evidence that rofecoxib differed
      from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores
      in overlapping subgroups of patients who had Mini Mental State Exam scores of 24
      26 in the present MCI study and in a previous AD treatment study with a similar
      design. The results from this MCI study did not support the hypothesis that
      rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects
      observed in previous AD studies, the findings suggest that inhibition of COX-2 is
      not a useful therapeutic approach in AD.

PMID- 15742006
TI  - Trabeculectomy around the globe.

PMID- 15742008
TI  - [Epidemiological data on multiple sclerosis].

PMID- 15742007
TI  - [No shame to turn].

PMID- 15742009
TI  - [Cancer patients should not feel pain].

PMID- 15742010
TI  - [Cancer pain in hospitalized patients].
AB  - BACKGROUND: In spite of increased knowledge in palliative care, there are still
      cancer patients who do not receive adequate pain relief. There is limited
      information on cancer pain experience in Norwegian hospitals. More data is needed
      in order to understand why barriers still exist to adequate pain management.
      MATERIAL AND METHODS: We performed a one-day prevalence study of cancer pain in
      all hospitalized patients in the southern health region of Norway. A
      questionnaire based on the Brief Pain Inventory was used. RESULTS: 309 patients
      were included. 40% used no analgesics. 51 % reported having pain while
      hospitalized; mean pain level on the visual analogue scale over the last 24 hours
      was 2.6. 70 patients reported strong to intolerable pain (visual analogue scale >
      or = 5), and 27 of these patients did not use opioids. 104 patients reported
      symptoms consistent with neuropathic pain, but only 7 used relevant co
      analgesics. 102 patients reported break-through pain. Patients with neuropathic
      pain and break-through pain scored significantly higher on pain and significantly
      worse on all global variables like quality of sleep, daily activity, and ability
      to work. INTERPRETATION: Many cancer patients still have pain, possibly because
      of inadequate medication. Key words for improvement are better knowledge, higher
      professional awareness, and systematic symptom assessment and pain analysis.

PMID- 15742011
TI  - [The patient experiences questionnaire PasOpp in somatic outpatient clinics].
AB  - BACKGROUND: The purpose of this paper is to describe the development and
      evaluation of the patient experiences questionnaire (PEQ) for somatic
      outpatients. MATERIAL AND METHODS: Literature review, focus groups, interviews
      with patients and clinicians, and pre-testing of questionnaire items were used. A
      postal survey among 12,525 patients of 23 outpatient clinics for adults in two
      Norwegian health regions was conducted during 2003. RESULTS: 6824 (55%) patients
      responded to the questionnaire. Low levels of missing data suggest that the
      questionnaire is acceptable to patients. Factor analysis of items deemed
      applicable to all patients produced three scales: clinic access (2 items),
      communication (6 items) and organisation (4 items). The remaining items
      contributed to the hypothesised scales of information (6 items), hospital
      standards (3 items), and pre-visit experience (3 items). With the exception of
      the pre-visit experience scale, the levels of Cronbach's alpha met the criterion
      of 0.7. The great majority of the results of validity testing were as
      hypothesised. Correlations between the scales ranged from 0.30 (clinic access and
      information) to 0.72 (communication and information). As hypothesised, scores
      were significantly related to responses to questions about overall satisfaction,
      general health, and age. INTERPRETATION: The outpatient experience questionnaire
      is a self-administered instrument that includes the most important aspects of
      experience from the outpatients' perspective. Three core dimensions for use in a
      shortened version have been identified.

PMID- 15742012
TI  - [Optic neuritis--diagnosis, treatment and follow up].
AB  - A national group of neurologists and ophthalmologists have evaluated guidelines
      and recommendations for diagnosis, treatment and follow up of optic neuritis
      based on clinical experience and a review of relevant literature. Optic neuritis
      is a common, well characterised condition that appears as an isolated syndrome or
      as a manifestation of multiple sclerosis. Several other diseases must be
      considered for a differential diagnosis. Corticosteroid treatment of optic
      neuritis has been investigated in a number of trials, which show that
      corticosteroid treatment speeds up the recovery of vision without affecting the
      final visual outcome. The diagnostic procedure and the treatment options have
      changed over the last few years. Some aspects of investigation, treatment and
      follow up are still controversial.

PMID- 15742013
TI  - [Optic nerve sheath meningeoma--from expectation to active treatment].
AB  - The management of optic nerve sheath meningeoma has been controversial and
      difficult. The conservative strategy was "to wait and see" until the patient
      became blind on the affected eye. Surgical excision had poor outcome and, with
      the exception of a few anecdotal case stories, led to blindness or postoperative
      eye motility disturbances. It has been long known that radiation therapy can
      prevent tumour progression, but the end result was very often visual
      deterioration and blindness. A few recent well documented studies describe how
      stereotactic fractionated conformal radiotherapy can provide stabilisation or
      improvement in the visual function in optic nerve sheath meningeoma. This article
      gives an overview, illustrated by a case story.

PMID- 15742014
TI  - [Occurrence of multiple sclerosis in Nordland, 1970-1999].
AB  - BACKGROUND: Epidemiologic data for multiple sclerosis in Nordland County in
      Norway has not been recorded for more than 50 years. MATERIAL AND METHODS: Cases
      between 1970 and 1999 were identified by diagnostic code searches in the files of
      Nordland Central Hospital, the county's only hospital with a department of
      neurology. Several cases from Nordland were also identified in hospital files in
      neighbouring counties. RESULTS: The raw prevalence of multiple sclerosis was
      determined to be 105.6 per 100,000 as at December 31, 1999. The crude annual
      incidence in the 1970-1999 period was 3.6 per 100,000 (95 % CI: 3.1-4.0). There
      was a pronounced rise in incidence from the late 1970s up until the early 1980s.
      From 1985 to 1999, the average annual incidence rate has been stable at 5.1 per
      100,000 (95 % CI: 4.4-5.8). INTERPRETATION: Compared to other Norwegian counties
      for which there are epidemiologic data, Nordland represents a medium risk zone
      for multiple sclerosis. The increase in incidence from the late 1970s to the
      early 1980s is most likely due to improved diagnosis and better record-keeping.

PMID- 15742015
TI  - [Are drugs past their expiration date dangerous?].

PMID- 15742016
TI  - [Effects of public initiatives aimed at reducing neural tube defects with folic
      acid supplementation].
AB  - BACKGROUND: In order to prevent neural tube defects, a daily supplement of 400
      microg (microgram) folic acid has been recommended in Norway since 1998, during
      the last month before conception and the first two or three months of pregnancy.
      Compliance with and effects of this recommendation has recently been evaluated in
      Norway in a report to the Directorate of Health and Social Welfare. MATERIAL AND
      METHODS: Reports published on periconceptional folic acid intake in Norway and
      some other countries from 1998 to autumn 2003 have been evaluated. RESULTS: In
      spite of several information activities, few Norwegian women start folic acid
      supplementation before verified pregnancy. The supplementation is started too
      late for the prevention of neural tube defects. A reduction is not observed in
      Norway. Internationally, information has not proven effective either, whereas
      compulsory fortification of foods with folic acid has been associated with
      reduced incidence. Information about periconceptional folic acid intake should be
      intensified. Compulsory fortification of foods with folic acid will affect the
      whole population, not only the target group of fertile women. If ongoing large
      intervention studies show improved clinical prognosis for patients with
      cardiovascular disease, this will be an additional argument for fortification of
      foods.

PMID- 15742017
TI  - [Does folic acid have effects on other health problems than neural tube
      defects?].
AB  - BACKGROUND: While it is widely accepted that periconceptional supplement of 400
      microg (microgram) folic acid reduces the risk of neural tube defects in
      pregnancy, it remains to be established whether folic acid has other beneficial
      effects on larger population groups. Evidence concerning effect of increased
      intake on cardiovascular disease, cancer and other diseases has recently been
      evaluated in a report to the Directorate of Health and Social Welfare in Norway.
      MATERIAL AND METHODS: Research reports published mainly from 1998 to 2003 on
      folic acid intake and disease have been evaluated. RESULTS: Sufficient evidence
      that increased folic acid intake may prevent cancer or cardiovascular diseases is
      not yet available, hence at present there is no indication for recommending
      augmented intake for other groups than fertile women. However, several
      intervention studies with folic acid supplementation are in progress to establish
      its effect on cardiovascular mortality and morbidity. INTERPRETATION: If the
      ongoing intervention studies show a beneficial clinical effect on cardiovascular
      disease, it would be a further argument for fortification of foods, in addition
      to reducing the risk of neural tube defects in pregnancy.

PMID- 15742018
TI  - [Fetal nutrition and future health].
AB  - Fetal nutrition may permanently affect physiological properties of the new
      individual and hence the risk of future disease. Epidemiological studies indicate
      that fetal nutrition may significantly influence the risk of diabetes,
      cardiovascular disease, and cancer. Controlled animal studies show that even
      properties traditionally considered as exclusively genetic, like fur colour, may
      be modified by altered maternal nutrition. The expression "fetal programming" has
      been introduced to describe permanent effects of environmental conditions in
      fetal life. An important mechanism of fetal programming seems to be epigenetic
      regulation. One example of epigenetic regulation is methylation of the DNA base
      cytosine in promoter regions of some genes. DNA methylation will lead to
      decreased gene expression. Over the last two decades, marked changes in dietary
      habits and other life style features have taken place among young Norwegian
      women. This is particularly reflected in the increasing prevalence of obesity.
      Maternal weight and metabolic status is closely associated with the growth and
      development of the fetus. Thus, diet and physical activity become particularly
      important aspects of the health of young women.

PMID- 15742019
TI  - [Fetal injury and alcohol drinking during pregnancy].
AB  - BACKGROUND: There is still an ongoing discussion whether moderate alcohol
      consumption during pregnancy is harmful to the fetus. In most western countries,
      however, total abstinence is recommended. MATERIAL AND METHODS: Over the last
      five years we have seen 64 infants and children with alcohol-related disorders.
      We present the clinical records of one alcohol-damaged child, and present the
      latest recommended categorisation of alcohol-related disorders in infants and
      children. RESULTS: In our experience, some women with heavy alcohol consumption
      are allowed to continue their abuse without interference from health
      professionals. Children of women with moderate alcohol consumption may be
      seriously damaged. Updated research on pregnancy and alcohol that we have
      reviewed provide clear evidence that brain structure as well as brain function
      are affected by heavy prenatal alcohol exposure. INTERPRETATION: Use of alcohol
      in pregnancy, also in moderate amounts, is a serious risk factor for fetal
      damage. Therefore complete abstinence from alcohol during pregnancy should be
      recommended. For the alcohol-damaged children, early recognition and appropriate
      treatment will give the child a better opportunity for future optimal
      development.

PMID- 15742020
TI  - [A programme for boosting medical research in North Norway, 1992-2001].
AB  - BACKGROUND: Goals for the programme were recruitment of specialists and lowering
      turnover among them, generating new knowledge, quality assurance and professional
      development. Close to NOK 25 million were spent on this research programme in
      regional non-university hospitals over the 1992-2001 period. MATERIAL AND
      METHODS: 78 projects were funded, 77 responded to our questionnaire. RESULTS: 36
      (47%) of respondents claim to have completed their projects, 5 (7%) have not,
      whereas 36 (47%) have ongoing projects. 70% of the projects have led to
      publications, 39% as part of doctoral theses, 61% have been done locally and 43 %
      also had other funding. In relation to the aims of the programme, those
      responding were very positive and 75 out of 77 suggested that a low-threshold,
      supportive programme of this type should be continued. INTERPRETATION: We
      conclude that the programme has had positive effects beyond the generation of new
      knowledge.

PMID- 15742021
TI  - [Revisiting the Forsdahl-Barker hypothesis].
AB  - The hypothesis about the influence of the environment in early life for later
      health and development has been the basis for several hundred studies over the
      last two decades. Despite some diverging results in different studies and
      methodological shortcomings, including selection and confounding from socio
      economic and other factors, there seems to be substantial evidence to the effect
      that the environment in early life is essential for later health and development.
      The association of low birthweight and risk of cardiovascular disease later in
      life is the most consistent finding, though the causal pathways for this
      connection have not been traced. Permanent damage caused by inadequate nutrition
      in critical periods of early life expressed as chronic disease later in life is a
      favoured hypothesis. To further elucidate potential mechanisms, there is a need
      for refining the measurement parameters for early experience. Placenta function,
      quality of nutrition, infections, hormonal and genetic factors may also play a
      role. The course-of-life approach claims that early life is an important period
      in human life, but not the only one. Continuous life events and socio-economic
      circumstances may modify early life experiences. Such an approach may be useful
      in order to see early life events in the right perspective.

PMID- 15742024
TI  - [Can Cesarean section be performed without maternal consent?].

PMID- 15742025
TI  - [Misunderstandings without limits].

PMID- 15742026
TI  - [Significance of cholesterol for cardiovascular disease mortality].

PMID- 15742027
TI  - [An interdisciplinary educational program about pulmonary obstructive disease in
      family practice].

PMID- 15742028
TI  - [Right to second opinion].

PMID- 15742030
TI  - [Interdisciplinary cooperation important in ADHD].

PMID- 15742032
TI  - [Kopenickiade?].

PMID- 15742033
TI  - [Ultrasound in the diagnosis of thyroid diseases].

PMID- 15742035
TI  - [Westin and windmills].

PMID- 15742037
TI  - [Research results and openness].

PMID- 15742038
TI  - [Important cardiovascular disease risk factors].

PMID- 15742040
TI  - [Handwashing and hand disinfection].

PMID- 15742042
TI  - Crystal engineering of porphyrin framework solids.
AB  - This article describes recent achievements made by us and other groups in
      targeted synthesis of porphyrin-based framework solids by various non-covalent
      mechanisms of molecular recognition. The self-assembly processes are effected in
      a tunable manner either by direct association of suitably designed porphyrin
      building blocks, or by their supramolecular aggregation through external linkers
      as metal ions and organic bi-dentate ligands. Many of these crystalline porphyrin
      materials exhibit open architectures and remarkable structural integrity, and
      their potential application for selective guest storage and molecular sieving is
      highlighted.

PMID- 15742043
TI  - Chiral molecular tapes from novel tetra(thiafulvalene-crown-ether)-substituted
      phthalocyanine building blocks.
AB  - A tetra(thiafulvalene-crown-ether) phthalocyanine self-assembles into helical
      tapes nanometers wide and micrometers long. Formation of these scrolled molecular
      architectures is a first for phthalocyanine fibres and shows potential as a novel
      conducting material.

PMID- 15742044
TI  - Molecular chairs, zippers, zigzag and helical chains: chemical enumeration of
      supramolecular isomerism based on a predesigned metal-organic building-block.
AB  - A predesigned metal-organic building-block [Cu(I)(2-pytz)](2-Hpytz = 3,5-di-2
      pyridyl-1,2,4-triazole) has been successfully used to synthesize four genuine
      supramolecular isomers.

PMID- 15742045
TI  - Supramolecular assemblies of DNA with neutral nucleoside amphiphiles.
AB  - A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM
      studies show that the three distinct structural components of the amphiphile
      (i.e, nucleobase, alkyl chains, and poly(ethylene glycol)) are required for the
      formation of DNA-amphiphile supramolecular assemblies on a mica surface.

PMID- 15742047
TI  - An unprecedented process involving normal and redox transmetallation reactions
      between Hg and Pt affording the unexpected K[Pt2[CH2C(O)Me]6(mu-Cl)3] complex:
      the key role of X-ray powder diffraction in unravelling its nature and structure.
AB  - [Hg{CH2C(O)Me}2] reacts with K[PtCl3(CH2=CH2)](2 : 1 molar ratio) to give
      K[Pt2{CH2C(O)Me}6(mu-Cl)3] (1); the intermediate [Pt{CH2C(O)Me}Cl2(CH2=CH2)]- has
      been detected in solution and isolated as a Me4N+ salt; the process occurs
      through successive normal and redox transmetallation reactions and an ab initio X
      ray powder diffraction study of has proven to be essential to establish its
      nature.

PMID- 15742046
TI  - Fine-tuning the degree of organic functionalization of mesoporous silica
      nanosphere materials via an interfacially designed co-condensation method.
AB  - A synthetic method that can fine tune the amount of chemically accessible organic
      functional groups on the pore surface of MCM-41 type mesoporous silica nanosphere
      (MSN) materials has been developed by electrostatically matching various anionic
      organoalkoxysilanes with the cationic cetyltrimethylammonium bromide micelles in
      a base-catalyzed condensation reaction of tetraethoxysilane.

PMID- 15742048
TI  - Mutual structure-directing effects of a non-interpenetrated square grid
      coordination polymer and its complementary complex anion net.
AB  - The cationic grid, {[Cu(1,2-bis(4-pyridylethane)2)(H2O)2]2+]n, and the complex
      anion, Cu(4-pySO3)4(H2O)2]2-, neither of which have been previously observed,
      form a perfectly complementary supramolecular pair with respect to charge and H
      bonding, to mutually stabilize each others formation.

PMID- 15742049
TI  - Mannose-substituted PPEs detect lectins: a model for Ricin sensing.
AB  - The interaction of a mannose-substituted poly(para phenyleneethynylene) (mPPE)
      with a lectin, Concanavalin A (ConA), is reported; the ConA causes fluorescence
      quenching of the mPPE with a K(SV) of 5.6 x 10(5).

PMID- 15742050
TI  - Inclusion of C60 into an adjustable porphyrin dimer generated by dynamic
      disulfide chemistry.
AB  - A new, highly flexible porphyrin dimer was isolated in preparative scale from a
      dynamic disulfide library; this receptor adjusts to fit guests with a wide range
      of steric requirements and, whilst C60 proved to be an unsuitable template for
      this library, a new C60-porphyrin complex was isolated and characterised.

PMID- 15742052
TI  - Fast and mild palladium(II)-catalyzed 1,4-oxidation of 1,3-dienes via activation
      of molecular oxygen with a designed cobalt(II) porphyrin.
AB  - The use of a Co(porphyrin)-amide ligand, , in the palladium(II)-catalyzed 1,4
      diacetoxylation of conjugated dienes under O2 results in aerobic oxidation. The
      catalyst was highly active under O2, and the 1,4-diacetoxylation reaction could
      also be performed under air.

PMID- 15742051
TI  - Supramolecular porphyrin-fullerene via 'two-point' binding strategy: axial
      coordination and cation-crown ether complexation.
AB  - A highly stable porphyrin-fullerene conjugate with defined distance and
      orientation, was formed using a newly developed 'two-point' binding strategy
      involving axial-coordination and cation-crown ether complexation; photochemical
      studies performed in benzonitrile revealed efficient charge separation and slow
      charge-recombination in the supramolecular complex.

PMID- 15742053
TI  - A switchable macrocycle-clip complex that functions as a NOR logic gate.
AB  - We have synthesized a new molecular switch-based on a macrocycle-clip complex
      whose switching behavior not only can be controlled through the use of either K+
      [2,2,2]cryptand or NH4+-Et3N systems but also provides color changes that are
      visible to the naked eye; consequently, this system operates as a two-input NOR
      functioning molecular logic gate.

PMID- 15742054
TI  - Switchable rewritability of Ag-TiO2 nanocomposite films with multicolor
      photochromism.
AB  - The photochromism and rewritability of Ag-TiO2 films were deactivated by
      modification with thiols to make it possible to retain color images displayed on
      the films (for more than 3 days under white fluorescent lamps), while the
      deactivated properties were fully reactivated by UV-irradiation.

PMID- 15742055
TI  - One teflon-like channelled nanoporous polymer with a chiral and new uninodal 4
      connected net: sorption and catalytic properties.
AB  - Zn(C17H8F6O4) is the first example of a fluoro-lined nanotube organo-inorganic 3D
      polymeric chiral structure, which possesses two different types of isolated
      channels, one of them being laid out with a double spiral of CF3-groups from the
      ligand molecule; the structure is a new uninodal 4-connected net that only exists
      when bent ligands connect the centres, and the compound exhibits selective
      sorption and catalytic chiral recognition properties.

PMID- 15742056
TI  - Structure controlled self-assembly of Cu(II) salicylic aldehyde and aldimine
      derivative complexes.
AB  - The order of self-assembled monolayers of Cu(II) salicylic aldehyde and aldimine
      complexes has been gradually changed by ligand substitution and the resulting
      nanostructures have been studied at the graphite/liquid interface using scanning
      tunneling microscopy.

PMID- 15742057
TI  - Silyl methallylsulfinates: efficient and powerful agents for the chemoselective
      silylation of alcohols, polyols, phenols and carboxylic acids.
AB  - Alcohols, phenols and carboxylic acids are silylated with very good yields in the
      presence of silyl methallylsulfinates under non-basic conditions and with the
      formation of volatile co-products.

PMID- 15742058
TI  - pi-Indenyl tin(II) and lead(II) compounds.
AB  - The syntheses and structures of the first indenyl-substituted tin(II) complexes,
      [Sn{1,3-(SiMe3)2C9H5}2] and [Sn(C5Me5)-{1,3-(SiMe3)2C9H5}], are described; the
      lead(II) analogue of the latter compound has also been prepared and structurally
      characterized.

PMID- 15742059
TI  - Microflow electroorganic synthesis without supporting electrolyte.
AB  - Anodic methoxylation of several organic compounds has been successfully achieved
      in the absence of intentionally added supporting electrolyte using an
      electrochemical microflow system.

PMID- 15742060
TI  - Expeditious synthesis of porphyrin-cobaltacarborane conjugates.
AB  - Two porphyrin-cobaltacarborane conjugates and were prepared in high yields via a
      nucleophilic ring-opening reaction of . These novel boron-rich and fluorescent
      compounds have potential application as boron delivery agents for the boron
      neutron capture therapy of tumors.

PMID- 15742061
TI  - A facile and versatile preparation of bilindiones and biladienones from
      tetraarylporphyrins.
AB  - Bilindiones and biladienones carrying aryl groups at the meso positions were
      prepared using coupled oxidation reactions of iron tetraarylporphyrins in 20-63%
      yield.

PMID- 15742062
TI  - An unexpected bonding interaction between dxy and a1u orbitals mediated by
      porphyrin deformation.
AB  - Through density functional calculation and NMR spectroscopy, an unusual
      intermediate-spin electronic structure (d(xz)d(yz))3(d(xy))1(d(z)2)1 has been
      assigned to the six-coordinate saddled [Fe(OETPP)(THF)2]+ complex instead of the
      corresponding ruffled [Fe(TiPrP)(THF)2]+ complex.

PMID- 15742063
TI  - An efficient synthesis of propargylamines via C-H activation catalyzed by
      copper(I) in ionic liquids.
AB  - A readily available copper(I) catalyst, in an ionic liquid, can effect three
      component coupling of aldehydes, amines and alkynes to generate propargylamines
      in high yields.

PMID- 15742064
TI  - Catalytic asymmetric allylation of aldehydes via a chiral indium(III) complex.
AB  - A chiral indium complex has been discovered to effect high enantioselectivities
      in the addition of allyltributyl stannanes to aldehydes. The allylation of a
      variety of aromatic, alpha,beta-unsaturated and aliphatic aldehydes resulted in
      good yields and high enantioselectivities (90-96% ee).

PMID- 15742065
TI  - Manganese(IV) dioxide-catalyzed synthesis of quinoxalines under microwave
      irradiation.
AB  - We synthesize quinoxalines, catalyzed by manganese(IV) dioxide, from a variety of
      alpha-hydroxyketones followed by trapping with aromatic or aliphatic 1,2-diamines
      without using a solvent, within one minute under microwave irradiation.

PMID- 15742066
TI  - Enantioselective chlorination and fluorination of beta-keto phosphonates
      catalyzed by chiral Lewis acids.
AB  - The direct chiral Lewis acidic enantioselective chlorination and fluorination of
      beta-keto phosphonates is presented; the chlorination proceeds in high yields and
      with up to 94% ee using NCS as the chloro source, while the fluorination with
      (PhSO2)2NF (NFSI) gives the optically active alpha-fluoro-beta-keto phosphonates
      in moderate to good yields and with up to 91% ee.

PMID- 15742067
TI  - Highly enantioselective dynamic kinetic resolution and desymmetrization processes
      by cyclocondensation of chiral aminoalcohols with racemic or prochiral delta
      oxoacid derivatives.
AB  - Cyclocondensation reactions of aminoalcohols and with racemic or prochiral delta
      oxoacid derivatives provide polysubstituted lactams with high enantioselectivity
      in a process that involves dynamic kinetic resolution and/or desymmetrization of
      enantiotopic or diastereotopic ester groups.

PMID- 15742068
TI  - Electrodeposition of ferrocenoyl peptide disulfides.
AB  - Using electrodeposition of cyclic and acyclic Fc-peptide disulfides tightly
      packed Fc-peptide monolayers were conveniently formed, which exhibit significant
      differences in their electron transfer kinetics.

PMID- 15742069
TI  - Anisotropic ion conduction in a unique smectic phase of self-assembled
      amphiphilic ionic liquids.
AB  - Two types of thermotropic smectic phase and of anisotropic ion conduction were
      observed in an amphiphilic ionic liquid, N-ethyl-N'-dodecylimidazolium dodecyl
      sulfonate/lithium tetrafluoroborate mixture.

PMID- 15742070
TI  - Asymmetric alkylation of dimethoxyphosphoryl-N-[1-(S)-alpha
      methylbenzyl]acetamide enolates. Synthesis of both stereoisomers from the same
      source of chirality by changing the equivalents of LDA.
AB  - A new methodology has been developed for the synthesis of both stereoisomers from
      a single chiral source.

PMID- 15742071
TI  - Evidence for the first oxidative insertion of a transition metal into a
      digallane(4): synthesis, structural characterisation and EPR studies of
      [Cp2Zr(III){Ga[N(Ar)C(H)]2}2][Li(THF)4], Ar = C6H3Pr(i)2-2,6.
AB  - Treatment of "ZrCp2" with the digallane(4), [{Ga[N(Ar)C(H)]2}2], Ar = C6H3Pri2
      2,6, in the presence of excess Bu(n)Li leads to the first example of a gallyl
      Group 4 complex, [Cp2Zr{Ga[N(Ar)C(H)]2}2][Li(THF)4], via an unprecedented
      oxidative insertion reaction; the paramagnetic complex has been characterised by
      X-ray crystallography and EPR spectroscopy.

PMID- 15742072
TI  - A pyrimidine-like nickel(II) DNA base pair.
AB  - 4-(2'-Pyridyl)-pyrimidinone deoxyriboside is synthesized and characterized as a
      DNA metallo base-pair; this novel nucleoside forms a self-pair in the presence of
      Ni(II) and stabilizes double helical DNA to the same extent as a G.C pair.

PMID- 15742073
TI  - Electrosynthesis of hydrogen peroxide in room temperature ionic liquids and in
      situ epoxidation of alkenes.
AB  - Hydrogen peroxide can be electrosynthesized from oxygen in [bmim][BF(4)]-water
      and used in situ for the epoxidation of alkenes.

PMID- 15742074
TI  - The first 4,1,10-MC2B10 supraicosahedral metallacarboranes and a route to
      previously inaccessible 4,1,12-ruthenium arene species.
AB  - Reduction of 1,12-closo-C2B10H12 or its C,C-dimethyl analogue with sodium in
      liquid ammonia followed by metallation with {CpCo}2+, {(arene)Ru}2+ or
      {(dppe)Ni}2+ fragments affords the first examples of 4,1,10-MC2B10 species;
      thermolysis of these yields the appropriate 4,1,12-MC2B10 isomers, unavailable
      for (arene)Ru metallacarboranes by similar thermolysis of known 4,1,6-MC2B10
      compounds.

PMID- 15742075
TI  - 1-Triflylpyrroles as efficient dienophiles in normal electron demand [4+2]
      cycloaddition reactions under pressure.
AB  - 1-Triflylpyrroles bearing acetyl group(s) on position 3, or 2 and 4, are
      efficient dienophiles in normal electron demand Diels-Alder reactions activated
      by high pressures and Lewis acids.

PMID- 15742076
TI  - Calix[4]arene-cholic acid conjugates: a new class of efficient synthetic
      ionophores.
AB  - The synthesis of a new class of amphiphilic calix[4]arene-based ionophores,
      relying on direct reductive amination as a key step, and the evaluation of their
      H+ and Na+ transporting properties is described.

PMID- 15742077
TI  - [Management of patients with acute pharyngitis].

PMID- 15742078
TI  - [Sequential microbiological monitoring of tracheal aspirates in intubated
      patients admitted to a pediatric intensive care unit].

PMID- 15742079
TI  - [Certainties and uncertainties about very-low-birthweight infants and nutritional
      status].

PMID- 15742080
TI  - [Well-child care: two distinct views].
AB  - OBJECTIVE: To present, in an essay form, two distinct views on well-child care.
      METHODS: Using several different methods of historical analysis, the two most
      common views on well-child care are presented: the positivist one, whose
      foundation is essentially based upon historical facts, and that of social
      criticism, concerned with how historical facts are inserted in society at
      different levels. RESULTS: The coexistence of two distinct views on well-child
      care reveals two conflicting ideologies, but it does not invalidate the two
      different types of knowledge. CONCLUSIONS: Even though the understanding of well
      child care through a historical approach does not allow for definitive
      conclusions on what it is or what it will be, it encourages reflections on more
      practical meanings, namely: the possibility to consider practices that gather an
      ensemble of positive knowledge without disregarding their limitations, and the
      formulation of well-child care practices concerned with social care, determined
      by several aspects, instead of by ideological interest.

PMID- 15742081
TI  - [Robin sequence: a single treatment protocol].
AB  - OBJECTIVE: To present a single protocol that might cover both the respiratory and
      feeding difficulties of neonates and infants with Robin sequence. SOURCES OF
      DATA: The article was prepared on the basis of the most recent publications
      available in bibliographic databases and in books that discuss the treatment of
      Robin sequence, especially the studies conducted at the Hospital for
      Rehabilitation of Craniofacial Anomalies of Universidade de Sao Paulo (HRAC/USP).
      SUMMARY OF THE FINDINGS: We present the morphological and genetic aspects of
      Robin sequence and concepts about nasopharyngoscopy and its clinical
      implications; we discuss the treatment of respiratory and feeding difficulties,
      and we present a single protocol for the treatment of all Robin sequence cases
      regardless of their severity and complexity. CONCLUSIONS: Robin sequence is not
      only an anatomic obstructive disorder to be treated with surgical procedures, but
      knowledge about children s growth and development must be applied by a
      multidisciplinary team, since this permits the maintenance of airway permeability
      and of the ability to feed orally, often without the need of surgical procedures
      and their risks, especially when applied to neonates and small infants.

PMID- 15742082
TI  - [Comparative analysis of clinical and laboratory methods for diagnosing
      streptococcal sore throat].
AB  - OBJECTIVES: Diagnosis and correct treatment of group A streptococcal sore throat
      is important particularly to prevent non-suppurative sequelae. Clinical findings
      continue to be used to differentiate streptococcal infection from viral sore
      throat. The American Academy of Pediatrics recommends that streptococcal sore
      throat diagnosis should always be performed by microbiological identification
      methods. The aim of this study is to evaluate the accuracy of clinical diagnosis
      in comparison with culture and rapid test. METHODS: Children aged 2 to 13 years
      who had received a clinical diagnosis of sore throat and sought treatment at the
      pediatric emergency unit of Sao Paulo Santa Casa were evaluated and those with
      clinical signs or viral infection were excluded. Clinical findings were recorded
      and swabs were taken for group A Streptococcus cultures and a Streptococcus rapid
      test. RESULTS: The culture was positive in 96 (24.4%) of the 376 children
      evaluated. The presence of petechiae, purulent exudate and painful tonsils were
      more likely to occur in children with positive streptococcus cultures, however
      they exhibited low diagnostic accuracy. The doctors' subjective evaluation failed
      to identify 21% of positive cases and antibiotics were prescribed in 47% of
      negative cases, compared with 3 and 6%, respectively, for the rapid test.
      CONCLUSIONS: A microbiologic method is necessary for the correct prescription of
      antibiotics in children with streptococcal sore throat.

PMID- 15742083
TI  - [Sequential microbiological monitoring of tracheal aspirates in intubated
      patients admitted to a pediatric intensive care unit].
AB  - OBJECTIVE: To evaluate, sequentially, tracheal aspirates from patients admitted
      to a pediatric intensive care unit and to associate these pathogens with length
      of hospital stay, previous use of antimicrobial therapy and diagnoses of
      ventilator-associated pneumonia. METHODS: The study population consisted of
      patients admitted to a pediatric intensive care unit, between November 2002 and
      December 2003, on ventilator support. Three tracheal aspirates were collected
      serially from each patient. The first tracheal aspirate sample was obtained 6
      hours after admission to the intensive care unit and the remaining samples were
      collected after 48 and 96 hours. RESULTS: One hundred patients aged from one day
      to 14 years were assessed. Positive tracheal cultures were observed to have
      increased in the three tracheal aspirate samples collected from each patient for
      Pseudomonas aeruginosa, from 6 to 22% (p = 0.002), and to have decreased for
      Staphylococcus aureus, from 23 to 8% (p = 0.009). Isolation of Candida spp
      increased for the subset that had received previous antimicrobial therapy (p <
      0.05). Sixteen (23.5%) out of 68 patients admitted without pneumonia developed
      ventilator-associated pneumonia. Positive tracheal aspirate cultures were
      obtained in 10 out of 16 of these patients: six were positive for Staphylococcus
      aureus (three associated with Acinetobacter baumanii), two for Klebsiella spp
      (one associated with Enterobacter spp), one for Pseudomonas aeruginosa and one
      for Candida spp. CONCLUSION: Sequential evaluation of tracheal aspirates may be
      useful to track changes in bacterial flora at pediatric intensive care units.

PMID- 15742084
TI  - [Evaluation of the nutritional status at 40 weeks corrected gestational age in a
      cohort of very low birth weight infants].
AB  - OBJECTIVE: To evaluate the nutritional status at term of a cohort of newborn
      babies with birth weights of less than 1,500 g and to correlate this with
      nutritional practices and clinical variables. METHODS: Very low birth weight
      infants admitted to eight neonatal intensive care units from November 1999 to
      April 2000 were studied prospectively. The units were defined as Type I if they
      employed aggressive nutritional support techniques and Type II if other
      nutritional practices were used. Babies were defined as malnourished if their z
      score for weight was less than or equal to -2 on the Canadian Perinatal
      Surveillance System growth curves. Data were analyzed using multivariate linear
      regression and logistic regression. The study was approved by the Committee for
      Ethics in Research. RESULTS: Sixty-three percent (126/200) of the study
      population were classified as being malnourished at term. Weight at term
      (corrected gestational age) showed a direct correlation with birth weight, but an
      indirect correlation with the length of stay, gestational age at birth, time to
      regain birth weight and CRIB score (p < 0.05). Small for gestational age infants
      had a 12.19 times greater chance of being malnourished at term. Being born at a
      Type I unit reduced the risk of malnutrition at term by 2.17 times, male sex
      reduced this risk by 0.4 times and achieving total enteral nutrition by the 10th
      day of life reduced it by 1.97 times (p < 0.03). CONCLUSIONS: The most effective
      means of preventing babies being malnourished at term is by encouraging perinatal
      practices aimed at preventing restricted intrauterine growth, in addition to
      giving priority to aggressive nutritional management.

PMID- 15742085
TI  - [Exogenous human albumin supplementation in total parenteral nutrition of
      critically ill newborns].
AB  - OBJECTIVE: In view of the controversies found in the literature, the present
      study was conducted to determine the effect of the use of exogenous human albumin
      on the nutritional status of newborn infants submitted to total parenteral
      nutrition. METHODS: Thirty critically ill newborn infants weighing less than
      2,500 g were divided into two groups: 15 infants receiving total parenteral
      nutrition without human albumin (C control group) and 15 with human albumin
      (group A). Total protein, albumin, prealbumin, and retinol-binding protein were
      determined at the beginning (3-4 days of postnatal age) and at the end of the
      study (10-11 days of postnatal age). On the seventh day of the study, nitrogen
      balance (retention) was measured. The following clinical parameters were
      evaluated: weight, age at the beginning of enteral nutrition, time to reach a
      full enteral volume, length of stay in the intensive care unit, total
      hospitalization time, and mortality. RESULTS: The results showed a significant
      difference (p < 0.05) in serum albumin and total protein levels (p < 0.05)
      between groups at the end of the study. Median albumin levels were 2.95 g/dl in
      group C (2.71-3.16 g/dl), whereas group A showed median albumin levels of 4.10
      g/dl, (3.76-4.66 g/dl). Total protein levels were 4.9 g/dl (4.4-5.2 g/dl) and 5.6
      g/dl (5.5-6.3 g/dl), respectively, with no repercussions on any of the remaining
      parameters evaluated. CONCLUSIONS: On the basis of the results obtained in the
      present study, no benefits were derived from the use of human albumin in total
      parenteral nutrition in severely ill newborns; therefore its use cannot be
      recommended, unless the objective is exclusively to elevate albumin levels.

PMID- 15742086
TI  - [Gestational weight gain and macrosomia in a cohort of mothers and their
      children].
AB  - OBJECTIVE: To identify co-variables potentially associated to infant macrosomia,
      including excessive gestational weight gain. METHODS: A cohort was investigated
      consisting of 230 pairs of mothers and children, residents of the City of Rio de
      Janeiro. Fetal macrosomia, defined as a birth weight > or = 4,000 grams was
      treated as the dependent variable. Statistical analysis of the relation between
      macrosomia and co-variables involved stratified analysis and multivariate
      logistic regression, which estimates odds ratios (OR) and 95% confidence
      intervals (CI 95%). RESULTS: The incidence of excessive gestational weight gain
      was 29.1%, varying from 10% for women under 20 years to 63.6% for women who had
      given birth to children with macrosomia. Macrosomia incidence was 4.8% for the
      group as a whole, 10.4% for women with excessive gestational weight gain and 2.5%
      for women with normal gestational weight gain. Women with excessive gestational
      weight gain and > or = 20 years exhibited a chance of developing macrosomia that
      was 5.42 times greater (CI 95%: 1.11-26.34). Within the final multivariate
      logistic regression model, only excessive gestational weight gain (OR = 5.83, CI
      95%: 1.51-22.48) remained associated to infant macrosomia. CONCLUSIONS:
      Considering that excessive gestational weight gain was the only predictor related
      to macrosomia, it is important that preventive programs that take account of this
      predictor be implemented, avoiding undesirable fetal outcomes. Future studies
      should include a wider variety of macrosomia predictors and additional birth
      outcomes.

PMID- 15742087
TI  - [Adaptation and validation of the Pediatric Asthma Quality of Life Questionnaire
      (PAQLQ) in Brazilian asthmatic children and adolescents].
AB  - OBJECTIVES: To translate the Pediatric Asthma Quality of Life Questionnaire
      (PAQLQ) into Portuguese and adapt it to the Brazilian context, for use in
      children and adolescents with asthma and to validate the adapted version of the
      questionnaire (PAQLQ-A). METHODS: Children and adolescents (7 to 17 years old)
      with asthma answered the PAQLQ-A on admission and were assessed using a clinical
      severity score. According to this score, patients were classified as mild (> or =
      2) or moderate/severe (< 2). They were reassessed on at least two occasions at an
      interval of 2 to 4 weeks. Furthermore, patients in whom asthma was properly
      controlled were classified as stable, and those in whom it could not be
      controlled, as unstable. RESULTS: The reproducibility of the PAQLQ-A was
      evaluated in stable patients by comparing the mean domain scores: symptoms,
      emotions, activities, and the overall clinical severity score on two predefined
      occasions with an interval of 15 to 30 days in between. Responsiveness was
      evaluated among unstable patients. The mean domain scores and the overall score
      were different on both occasions, and so was the clinical severity score. The
      validity of the questionnaire was determined by the application of Cronbach's
      alpha reliability coefficient (alpha = 0.909). CONCLUSIONS: The translation of
      the PAQLQ into Portuguese did not modify the framework of the original
      questionnaire; the PAQLQ-A is easy to use, with easy reproducibility,
      constituting a valuable instrument for the evaluation of the quality of life in
      children and adolescents with asthma.

PMID- 15742088
TI  - [The effect of processing on the Vitamin A content of human milk].
AB  - OBJECTIVES: To analyze the effect of processing on the Vitamin A levels of milk
      that is donated to the Human Milk Bank at the University Maternity Hospital, and
      to evaluate whether this milk supplies the infants' Vitamin A requirement.
      METHODS: Sixty milk samples from the Human Milk Bank were divided into two equal
      portions. One milk portion was extracted prior to processing, while another
      fraction was subjected to pasteurization and later extracted. The samples were
      analyzed using high performance liquid chromatography. Analysis with Student's t
      test indicated that the difference between mean retinol levels was statistically
      significant at the p < 0.05 level. RESULTS: The retinol content found in the milk
      prior to processing was 55.4+/-34.0 microg/100 ml, whereas for the processed milk
      this level was 36.6+/-26.1 microg/100 ml (p < 0.001). CONCLUSION: It was found
      that retinol loss occurs during milk processing and that the milk from the Human
      Milk Bank does not meet infants' Vitamin A requirement.

PMID- 15742089
TI  - [Bronchial provocation tests using methacholine, cycle ergometer exercise and
      free running in children with intermittent asthma].
AB  - OBJECTIVE: To compare airway responsiveness to methacholine, cycle ergometer
      exercise and free running in children with intermittent asthma. METHODS: A
      randomized study was conducted with 30 children of both genders with intermittent
      asthma. Each child was submitted to challenge testing on three separate days, in
      random order: a) Methacholine challenge using a dosimeter; b) Exercise challenge
      testing -- free running along a 50-meter-long corridor; c) Dry-air exercise
      challenge on a cycle ergometer. Target heart rate during exercise was 80 to 90%
      of the maximum predicted value. Spirometry was performed 3, 6,10,15,20 and 30
      minutes after exercise. Exercise-induced bronchospasm was defined as a decrease
      in FEV1 of > or = 10% in comparison to pretest values. RESULTS: Mean age was 11+/
      3 years. FEV1 and FEV1/FVC ratios were normal and similar before all provocation
      tests. The maximum heart rate was 178+/-7 bpm during cycling and 181+/-6 bpm
      during the free running test (p > 0.05). Significant bronchospasm was observed
      with methacholine in 23 cases, after free running in 19 and after cycling in 14
      children (p < 0.05, methacholine vs exercise tests). Taking all FEV1 measurements
      after exercise into account, the free running test resulted in greater exercise
      induced bronchospasm in comparison with exercise made on a cycle ergometer (p =
      0.003, chi2 = 8.948). There was a significant, but poor, correlation between the
      maximum percentage decrease in FEV1 after free running and cycling (r = 0.46, p <
      0.01). CONCLUSIONS: Methacholine challenge identifies a greater number of
      asthmatics in comparison to exercise tests. When bronchial provocation test with
      methacholine is not available, free running should be the test of choice due to
      its simplicity and greater ability to induce bronchospasm.

PMID- 15742090
TI  - American visceral leishmaniasis (kala-azar) in hospitalized children from an
      endemic area.
AB  - OBJECTIVE: To study epidemiological and clinical aspects of American visceral
      leishmaniasis in hospitalized children in Ceara, Brazil. METHODS: A retrospective
      and observational study was carried out with children suffering from American
      visceral leishmaniasis admitted to Hospital Infantil Albert Sabin in Fortaleza.
      Medical records were reviewed consistently. Inclusion criteria were children with
      amastigote-positive smears in bone marrow or in splenic aspirates, or a positive
      Leishmania sp immunofluorescence assay. RESULTS: From January 1995 to December
      2002, 450 children with American visceral leishmaniasis were identified,
      accounting for 9 to 27% of all reported cases in Ceara in that period, with peak
      hospitalization rates in 1995 and 2000. The mean age was 4.4 years (12% < 1 year
      and 65% < 5 years of age). The overall male: female ratio was 1.1 and 1.48 in
      children > 5 year (p = 0.04). Urban patients infected by American visceral
      leishmaniasis increased steadily over an 8-year period (chi2 p = 0.01). The main
      clinical complaints on admission were fever (96%), pallor (90%) and abdominal
      swelling (75%). Clinical cure was defined as the absence of fever, regression of
      splenic and hepatic enlargement and of pancytopenia. Overall mortality was 9.2%
      and 21.2% in patients younger than one year. Malnutrition, edema, bleeding,
      jaundice, and concomitant infections were related to higher mortality.
      CONCLUSIONS: Cases of American visceral leishmaniasis spiked with a 5-year
      interval, and affected most under-five urban children. Mortality was related to
      low age, signs of severe disease and concomitant infection.

PMID- 15742091
TI  - [Etiological assessment of hyperthyrotropinemia in children with Down's
      syndrome].
AB  - OBJECTIVE: To study the prevalence of increased TSH level and its probable cause
      in children with Down's syndrome treated at Policlinica Antonio Candido. METHODS:
      The data were collected using medical records of 169 patients. Of these, 46
      patients, whose TSH increased at some time during their follow-up, were re
      evaluated. In these patients, TSH, free T4, total T4 and thyroid peroxidase
      autoantibody (anti-TPO) levels were measured. Thyroid ultrasound, iodine-131
      scintigraphy, and a perchlorate discharge test were performed. RESULTS: In 169
      children, 86 (50.8%) of whom were male, aged between 1-16 years (median 4 years),
      67 (39.6%) presented increased TSH levels. Out of these 67 patients, 46 were
      prospectively studied. In 31 (67.4%) of them serum TSH returned to normal levels;
      in 11, TSH remained between 5 and 10 microU/ml, three (6.5%) had a TSH level over
      10 microU/ml and one (2.2%) had hyperthyroidism. The diagnoses in 34 patients who
      were fully studied were: goiter in five (14.7%); Hashimoto's thyroiditis in four
      (5.9%); hypoplasia in three (8.8%) and iodide organification defect in one
      (2.9%). The increased TSH levels had a statistically positive relationship with
      anti-TPO (p = 0.02), but not with gender, abnormal ultrasound or scintigraphy
      findings. TSH levels did not have any relationship with persistent
      hyperthyrotropinemia. CONCLUSIONS: In patients with Down's syndrome, slightly
      elevated and transient TSH levels are frequently detected. Positive anti-TPO
      antibody test is a key factor in the follow-up of these patients because of its
      potential risk of progression to manifest thyroid disease.

PMID- 15742093
TI  - Comparing asthma prevalence estimates in Recife.

PMID- 15742095
TI  - [Lung deposition, efficacy and clinical effectiveness of spacer devices].

PMID- 15742096
TI  - [Conjugated and polysaccharide anti-pneumococcal vaccines].

PMID- 15742097
TI  - [Ophthalmomyiasis as a cause of canalicular lesion].
AB  - OBJECTIVE: Myiasis is the invasion of human tissues by Diptera larvae. Ocular
      involvement is uncommon. Trauma is the major cause of lacrimal apparatus lesions.
      However, it is rarely associated with parasitic infestation. The objective of
      this paper is to report a case of canalicular laceration caused by Dermatobia
      hominis larva. DESCRIPTION: An eight-year-old girl presented preseptal cellulitis
      that was refractive to antibiotics. A Dermatobia hominis larva was observed
      inside the lacrimal sac. Surgical extraction was performed and laceration of the
      lacrimal drainage system was noted. COMMENTS: Parasitic infection of the lacrimal
      apparatus is rare. Surgical extraction is the treatment of choice in such cases.
      Despite being uncommon, ophthalmomyiasis should be considered as a possible
      diagnosis when cellulitis is not responsive to antibiotics, especially in endemic
      areas. This is the first description of lacrimal drainage system injury by
      Dermatobia hominis larva.

PMID- 15742100
TI  - The R495W mutation in SPG3A causes spastic paraplegia associated with axonal
      neuropathy.
AB  - Mutations in the SPG3A gene cause a form of pure, early-onset autosomal dominant
      hereditary spastic paraplegia linked to chromosome 14q. The encoded protein,
      atlastin, is a putative member of the dynamin superfamily of large GTPases
      involved in cellular trafficking patterns. We report a new atlastin mutation
      causing spastic paraplegia in association with axonal neuropathy in an Italian
      family.

PMID- 15742101
TI  - Acute hepatitis secondary to interferon beta-1a in multiple sclerosis.

PMID- 15742098
TI  - [One decade of functional imaging in schizophrenia research. From visualisation
      of basic information processing steps to molecular-genetic oriented imaging].
AB  - Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and
      positron emission tomography (PET) have contributed tremendously to our current
      understanding of psychiatric disorders in the context of functional, biochemical
      and microstructural alterations of the brain. Since the mid-nineties, functional
      MRI has provided major insights into the neurobiological correlates of signs and
      symptoms in schizophrenia. The current paper reviews important fMRI studies of
      the past decade in the domains of motor, visual, auditory, attentional and
      working memory function. Special emphasis is given to new methodological
      approaches, such as the visualisation of medication effects and the functional
      characterisation of risk genes.

PMID- 15742102
TI  - Autosomal recessive progressive myoclonus epilepsy with ataxia and mental
      retardation.
AB  - We describe two couples of sibs from a southern Italian family affected by
      epilepsy, myoclonus, mental retardation and slight ataxia. Onset was between 4
      and 12 years and the course slowly progressive. The clinical picture suggested
      the diagnosis of Unverricht-Lundborg disease. Molecular study excluded linkage to
      EPM1. Other possible causes of progressive myoclonus epilepsy were also excluded.

PMID- 15742103
TI  - Isolated myopathy as the initial manifestation of primary systemic amyloidosis.

PMID- 15742105
TI  - Plasmapheresis improves the outcome of central pontine myelinolysis.

PMID- 15742104
TI  - Cognitive function in bulbar- and spinal-onset amyotrophic lateral sclerosis. A
      longitudinal study in 52 patients.
AB  - We performed a longitudinal study of frontal and temporal lobe functions in
      patients with amyotrophic lateral sclerosis (ALS) and compared the evolution of
      cognitive performance with that of motor deficits in patients with spinal and
      bulbar-onset of the disease. Fifty two patients suffering from sporadic ALS
      according to the El Escorial criteria were examined; 37 patients had a spinal, 15
      a bulbar onset of the disease. The data profile included examinations at entry
      (E1), every four months at follow-up (E2, E3, E4) and after 18 months (E5), if
      possible. Neuropsychological testing covered the domains of executive functions,
      memory and attentional control. ALS patients showed executive dysfunctions that
      were most prominently represented by deficits of non-verbal and verbal fluency
      and concept formation. Memory-related deficits were also present but less
      expressed. The same held true for phasic and tonic alertness and divided
      attention. In contrast to motor functions declining concomitantly with disease
      progression, cognitive deficits appeared in early disease, were essentially
      present at initial testing and did not substantially decline on follow-up. A
      subgroup analysis revealed that bulbar-onset ALS patients performed consistently
      poorer in many cognitive tests than spinal-onset ones with special reference to
      verbal and non-verbal fluency and interference control. This subgroup difference
      persisted or even increased throughout follow-up. We conclude that there is a
      fronto-temporal pattern of cognitive dysfunction in ALS expressing itself early
      in the course of the disease and mainly with bulbar forms. The cognitive deficits
      do not progress in synchrony with motor decline, but distinctly more slowly. We
      suggest that cognitive dysfunctions reflect functional and possibly morphological
      deficits outside the primary motor system that is specific for the nature and
      evolution of the disease and might also give clues to etiopathogenesis.

PMID- 15742106
TI  - Current treatments in neurology: stroke.
AB  - There have been major advances in stroke treatment based on robust evidence from
      large clinical trials. This review covers both acute treatment and secondary
      prevention. Thrombolysis is now established as a therapy for ischaemic stroke
      presenting within 3 hours, and the possibility of extending the time window and
      refining the selection of suitable patients, is being addressed in further
      trials. Anticoagulants are of proven benefit in cardioembolic stroke, and
      particularly atrial fibrillation. For prevention of other stroke subtypes
      antiplatelet agents appear to have a better risk-benefit ratio. Evidence for the
      use of dual antiplatelet therapy, including the recent MATCH study, are
      discussed. Carotid endarterectomy is of proven benefit in patients with>70%
      symptomatic stenosis. Recent analysis has emphasised the importance of operating
      as soon after symptom onset as possible. Operating on asymptomatic carotid
      stenosis remains controversial; even after the recent Asymptomatic Carotid
      Surgery Trial which showed that by operating on 32 people one disabling stroke or
      death could be prevented over a 5 years period.

PMID- 15742107
TI  - Effects of levetiracetam on the production of nitric oxide--an in vivo study.

PMID- 15742108
TI  - Wilson's disease-cause of mortality in 164 patients during 1992-2003 observation
      period.
AB  - We studied the cause of death in a consecutive series of 164 patients with
      Wilson's disease (WD) diagnosed over an 11 year period. A total of 20 [12% (95%
      CI 10.3-16.0)] died during the observation period. The relative survival rate of
      all patients in our group was statistically smaller than in Polish population.
      The main cause of death was the diagnosis in advanced stage of disease, but in
      six patients presenting with mild signs, we observed the progression of the
      disease despite treatment. There was no difference in mortality rate in patients
      treated with d-penicillamine or zinc sulphate as initial therapy. The prognosis
      for survival in the majority of WD patients is favourable, provided that therapy
      is introduced early.

PMID- 15742109
TI  - Clinicopathological aspects of the neuropathy of neurogastrointestinal
      encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie
      Tooth presentation.
AB  - We report on four patients with severe polyneuropathy associated with intestinal
      pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear
      ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and
      dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy
      specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation.
      All three were heterozygous for a recessively transmitted double substitution in
      the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp.
      The fourth patient, who was the only patient of this series with an affected sib,
      had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no
      TP gene mutation and or morphological abnormalities of mitochondria on electron
      microscopic examination. He was the only patient of this series with an affected
      sib. The three patients with the full MNGIE syndrome died before the age of 30
      years. Detailed results of nerve pathology show that severe axonal degeneration
      is associated with segmental abnormalities of the myelin sheath in this syndrome
      which appears genetically heterogeneous. Our findings suggest that only
      ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to
      the mitochondriopathy.

PMID- 15742110
TI  - Functional, cognitive and emotional long-term outcome of patients with ischemic
      stroke requiring mechanical ventilation.
AB  - Prognosis of patients with ischemic stroke requiring mechanical ventilation (MV)
      has been reported to be poor. However, longterm survival and functional outcome
      have scarcely been studied and nothing is known about the prevalence of cognitive
      impairment or depression in survivors and their quality of life (QoL). We
      identified all patients treated for acute ischemic stroke on a Neurological
      Intensive Care Unit during 3.5 years who required MV for more than 24 hours.
      Early mortality rate at 2 months and survival rates at 1 and 2 years were
      determined. Survivors were examined for functional outcome (modified Rankin Scale
      (mRS), Barthel Index), cognitive impairment (Mini Mental State Examination
      (MMSE)), depression (Beck Depression Inventory, BDI) and QoL (Short Form-36).
      Clinical characteristics on admission were analyzed for prognostic significance.
      Of 101 consecutive patients, 44% died within 60 days. Survival rates at 1 and 2
      years were 40% and 33%, respectively. Age > 60 years (p = 0.002) and Glasgow Coma
      Scale score < 10 on admission (p = 0.002) were independent predictors of early
      and late mortality. History of myocardial infarction (p = 0.007) independently
      predicted late mortality at 2 years. Of 33 surviving patients, nine (27%) had a
      good functional outcome (mRS 0-2). Of 27 survivors who could be interviewed, 17
      (63%) had no cognitive impairment (MMSE > 24) and 20 (74%) did not suffer from
      relevant depression (BDI < 19). In conclusion, longer-term survival of patients
      with ischemic stroke requiring MV was 33% and every fourth survivor resumed an
      independent life without dementia or depression. Older patients comatose on
      admission and with concomitant cardiovascular disease had the lowest probability
      of a favorable outcome.

PMID- 15742111
TI  - Comparison of different MR venography techniques for detecting transverse sinus
      stenosis in idiopathic intracranial hypertension.
AB  - Cerebral venous outflow abnormalities, as transverse sinuses (TSs) stenosis,may
      underlie a picture of idiopathic intracranial hypertension (IIH). To identify the
      best non-invasive MR venography (MRV) technique for exploring the disturbance of
      flow of TSs in IIH patients, we compared three dimensional phase contrast (3-DPC)
      MRV images, acquired with different velocity encodings (15 and 40 cm/s) with two
      dimensional time-of-flight (2D-TOF) MR images in 6 subjects with IIH and 12 age
      matched normal controls. In both groups, we also measured flow velocity in TSs by
      using single slice 2D-CINE PC acquisitions. In all subjects with IIH, 3D-PC
      showed marked flow disturbance in the mid-lateral portion of both TSs when
      velocity encoding (VENC) was set to 15 cm/s while only a slightly irregular flow
      in TSs was detected when VENC was set to 40 cm/s or when 2D-TOF was used. By
      contrast, 3D-PC (VENC 15 and 40) and 2D-TOF techniques were comparable in
      detecting TS signal flow in normal controls. Measures of flow velocity, by using
      2D-CINE PC, revealed a three-fold increase of velocity at the level of the flow
      disturbance in IIH patients compared to normal controls (p<0.0001), suggesting a
      marked stenosis of mid-lateral portion of TSs in these patients. Setting the VENC
      to 15 cm/s on 3D-PC MRV may represent the best technical approach for visualizing
      disturbances of flow in TSs in subjects with symptoms suggestive of IIH.

PMID- 15742112
TI  - The use of the Actiwatch-Neurologica system to objectively assess the involuntary
      movements and sleep-wake activity in patients with mild-moderate Huntington's
      disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder characterised by
      cognitive, psychiatric and motor abnormalities including a range of involuntary
      movements. Currently, assessment of these movements involves the use of
      subjective rating scales such as the Unified Huntington's Disease Rating Scales
      (UHDRS) for bradykinesia and maximal dystonia and chorea, without any objective
      measures. As new therapies emerge, it is critical that an objective means of
      evaluating these abnormal movements is developed and we have investigated the use
      of a wrist-worn activity monitor, the Actiwatch-Neurologica, to determine whether
      these movements can be measured. In addition, this activity monitor and
      subjective reports were used to objectively measure the degree of sleep
      disruption in these same HD patients. Eight patients with mild-moderate HD and 8
      age- and sex-matched control subjects wore the monitor for a period of 48 hours
      and recorded in a diary whether they were asleep or awake for each hour over the
      2-day period. Assessment of various movement parameters revealed that HD patients
      exhibited significantly greater total and maximum activity levels and spent
      longer performing high acceleration movements while they were awake compared with
      controls. During sleep, patients not only showed significantly more activity and
      spent more time making high acceleration movements, but they also made
      significantly more movements than control subjects. These results demonstrate
      that the Actiwatch-Neurologica activity monitor can be used to objectively assess
      movements in HD patients during periods of high activity as well as during sleep.

PMID- 15742113
TI  - Commentary on "A genome wide linkage disequilibrium screen in Parkinson's
      disease" by Foltynie et al. in J Neurol (2005) 252:597-602.

PMID- 15742114
TI  - No evidence for association of the protein kinase C alpha gene with multiple
      sclerosis.

PMID- 15742115
TI  - Phobic postural vertigo--a long-term follow-up (5 to 15 years) of 106 patients.
AB  - One hundred and six patients diagnosed between 1987 and 1998 to have somatoform
      phobic postural vertigo were examined in a follow-up study with a self-evaluating
      questionnaire. The improvement rate after a mean follow-up time of 8.5 years (5
      to 15.9 years) was 75% (27% of the patients reported a complete remission). While
      the majority of these patients experienced improvement or remission during the
      first year after assessment of diagnosis and a short-term psychotherapeutic
      approach, some patients also had considerable improvement even after two or more
      years. There was a negative correlation between the duration of the condition
      before assessment of the diagnosis and the improvement/regression rate. The
      improvement/regression rate was independent of gender, age, preceding vestibular
      or non-vestibular organic disorders, and the various medical, physical, or
      psychotherapeutic interventions. Transient relapses occurred in 47% of the
      improved patients once or repeatedly. The probability of developing a relapse
      remained constant throughout the entire follow-up. None of the patients required
      a revision of the initial diagnosis on the basis of the questionnaire.

PMID- 15742116
TI  - Commentary on "Neurology training in the UK: a diagnostic analysis of over 5000
      patients" by Maddison in J Neurol (2005)252: 605-607.

PMID- 15742117
TI  - Neurology training in the United Kingdom: a diagnostic analysis of over 5000
      patients.

PMID- 15742118
TI  - Generalized myositis mimicking polymyositis associated with chronic active
      Epstein-Barr virus infection.
AB  - BACKGROUND: Chronic generalized myositis has not so far been reported as a
      complication of chronic active Epstein-Barr virus infection (CAEBV). We
      encountered three patients with chronic generalized myositis mimicking
      polymyositis associated with CAEBV. METHODS: To clarify the pathological
      character of this myositis, we investigated the distribution, clonality, and the
      immunophenotype of EBV-infected cells and lymphocytes infiltrating in muscles.
      RESULTS: Clinically, two patients showed symmetrical proximal weakness and muscle
      atrophy as the initial and main symptom. Although the condition resembled
      polymyositis, they had also lingual and/or orbital myositis. The other patient
      showed generalized myositis at the late phase of CAEBV. In all of them,
      immunotherapy was ineffective and prognosis was poor. Intramuscular infiltrating
      lymphocytes in our patients were mainly CD45RO+, CD3+, CD4-, CD8-, TCR betaF1-,
      TCR deltaTCS1-, CD56-, CD79a-, CD21-, HLA-DR+, ZEBRA -, LMP1-, and EBER+ T cells.
      Oligoclonal expansion of EBV-infected T cells was shown in the muscles. However,
      there were no malignant lymphocytes. CONCLUSIONS: This new form of myositis must
      be distinguished from polymyositis and the other conventional forms of myositis.
      Careful investigation of hidden CAEBV is recommended when patients present with
      steroid non-responsive chronic progressive generalized myositis, in particular,
      with lingual or orbital involvement.

PMID- 15742119
TI  - Midline intravaginal slingplasty for treatment of urinary stress incontinence:
      results of an independent audit up to 2 years after surgery.
AB  - Recently, the midline intravaginal slingplasty (anterior IVS) directed at
      reinforcing the pubourethral ligament was introduced for treatment of urinary
      stress incontinence. An independent telephone interview to evaluate urinary
      symptoms and surgery-related changes in quality of life was performed between 12
      and 32 months after surgery. Of 52 women initially enrolled, 3 were lost during
      follow-up. None of the patients experienced infection, rejection or erosion of
      the tape. The procedure failed in 7 patients whereas in 42 patients cure of
      stress incontinence was achieved. This was not only verified by clinical
      examination at initial follow-up but also confirmed by the patients at the time
      of the interview. Although about two-thirds of the patients reported urge
      incontinence and/or voiding difficulties during their interview, the validation
      of the surgery was rather high and only in a minority did urinary complaints
      translate into reduced quality of life.

PMID- 15742120
TI  - From scleredema to AL amyloidosis: disease progression or coincidence? Review of
      the literature.
AB  - Scleredema (also called scleredema of Buschke) is a fibromucinous connective
      tissue disorder of unknown cause that belongs to a group of scleroderma-like
      disorders. We report the case of a 64-year-old lady with long-standing
      scleredema, associated with a paraprotein, and progressing to multiple myeloma
      and AL amyloidosis. The relationship of scleredema with paraprotein and multiple
      myeloma is well established, but only two cases of scleredema associated with
      amyloidosis have been reported to date. We suggest that amyloidosis may be
      underdiagnosed in patients with scleredema and paraproteinaemia. Features
      attributed to extracutaneous manifestations of scleredema could represent
      systemic amyloidosis. We review published reports of scleredema associated with
      paraprotein and discuss the difficulties in the differential diagnosis of
      scleroderma-like disorders. We discuss the diagnosis of plasma cell dyscrasias
      and amyloidosis and their relevance in rheumatology practice.

PMID- 15742121
TI  - Relationship between clinical factors and neuropsychiatric manifestations in
      systemic lupus erythematosus.
AB  - Neuropsychiatric symptoms are often seen in patients with systemic lupus
      erythematosus (SLE). To investigate the relationship between involvement of the
      nervous system and clinical factors, including autoantibodies and the activity of
      SLE, we retrospectively reviewed 25 patients with neuropsychiatric SLE (NPSLE,
      mean age: 35.2+/-12.2 years). As controls 37 SLE patients without
      neuropsychiatric manifestations (mean age: 31.8+/-15.8 years) were employed in
      this study. At the onset no significant differences were seen in any clinical
      factors between the patients and the controls except for serum antinuclear
      antibodies. In relapse, the patients with NPSLE showed significantly lower levels
      of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores without
      neuropsychiatric evaluation (p<0.0001), erythrocyte sedimentation rate (ESR,
      p<0.005), and antinuclear and anti-double-stranded DNA antibodies (p<0.005) and
      higher WBC values (p<0.05) than at the onset. Also in the patients with relapsing
      NPSLE similar significant differences were seen in these parameters between onset
      and relapse (p<0.005). Despite a lack of significant differences, the
      cerebrospinal fluid showed lower values in cell counts, total protein, and IgG in
      relapse than at onset. These results suggest that there are no clinical factors
      that predict the development of NPSLE and that relapse can occur with low disease
      activity in the nervous system even with an inactive state of other organ
      involvement. Since NPSLE may suddenly relapse with a slight change in common
      disease activation markers, including inflammatory reactions, autoantibodies, and
      complements in serum and CSF findings, adequate corticosteroid and/or
      immunosuppressive agents should be given at the onset and gradually be tapered
      after recovery, while looking out for recurrence.

PMID- 15742122
TI  - Effects of simvastatin on bone mineral density and remodeling parameters in
      postmenopausal osteopenic subjects: 1-year follow-up study.
AB  - Observational studies suggest that statin use may be associated with lower
      incidence of fracture. However, there are conflicting data for their effects on
      bone remodeling parameters and bone mineral density (BMD). In the present study,
      we aimed to investigate the effects of simvastatin on bone metabolism and BMD in
      subjects with hypercholesterolemia (>240 mg/dl). For this purpose, 32
      postmenopausal osteopenic subjects who were given simvastatin treatment (20
      mg/day) and not on osteoporosis treatment were included in the study. During the
      1-year follow-up period, the total cholesterol level decreased from 262.1+/-30.9
      to 202.2+/-30.1 mg/dl (p<0.0001). At a period as early as the 3rd month, levels
      of the anabolic markers, e.g., bone-specific alkaline phosphatase (BSAP) and
      osteocalcin (OCL), were found to be significantly increased (from 120.8+/-56.6 to
      149.5+/-57.6 IU/l, p=0.008, and from 20.8+/-12.6 to 34.7+/-18.4 microg/l,
      p=0.015, respectively) while no significant change was observed in the resorptive
      marker of serum N-telopeptide of type I collagen (CTX). At the 6th and 12th
      month, BSAP and OCL were both found to be decreased below the pretreatment
      values. While a significant reduction was found in BSAP levels (from 120.8+/-56.6
      to 55.9+/-18.8 IU/l, p<0.001), no significant change was observed in CTX levels
      after the 6-month treatment period. Parathyroid hormone showed a gradual profound
      increase during the follow-up period (from 62.7+/-41.5 to 108.4+/-51.7 pg/ml,
      p<0.001). No significant change was found in BMD levels at the spine, femoral
      neck, Ward's triangle, and trochanter at the end of the 1-year follow-up period.
      In conclusion, simvastatin treatment showed a short-lasting anabolic effect on
      bone metabolism. However, this effect was lost by prolongation of therapy. The
      decrease in both anabolic and resorptive markers at the 6th and 12th month
      suggests that simvastatin affects bone metabolism mostly in favor of inhibition
      of the bone turnover in a long-term observation period although this inhibitory
      effect was not reflected in BMD.

PMID- 15742123
TI  - Learning curve for laparoscopic Roux-en-Y gastric bypass with totally hand-sewn
      anastomosis: analysis of first 600 consecutive patients.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a challenging
      operation for the treatment of morbid obesity with well-demonstrated
      effectiveness in weight lost. There are several variations to the technique.
      METHODS: From September 2000 to July 2004, 600 consecutive patients underwent
      surgery for morbid obesity at our institution. The surgical technique employed
      was LRYGB with totally hand-sewn gastrojejunal anastomosis (GJA). All patients
      were considered candidates for laparoscopic approach regardless of age, gender,
      body mass index (BMI), or previous bariatric or digestive surgery. RESULTS: Mean
      BMI was 44.4 +/- 7.6 kg/m2. Thirty-two patients had undergone previous failed
      bariatric procedures. Conversion to an open procedure was necessary in three
      patients. Seventy-two patients (12%) developed early complications, including 23
      (3.8%) leaks at the GJA (eight in the first 18 patients). Mortality rate was 1.1%
      (one death was related to GJA leakage). Early and late reoperation rates were 5.3
      and 1.8%, respectively. Rate plateau of morbidity and mortality was reached after
      the first 18 patients when the surgical technique was fully standardized.
      CONCLUSIONS: LRYGB is a technically demanding procedure for the surgical
      treatment of morbid obesity with significant morbidity during the learning curve.
      The learning curve can be soon overcome, reaching a rate plateau of complications
      after adequate training. Morbidly obese patients should be operated on in expert
      bariatric surgical laparoscopic units to obtain the best results.

PMID- 15742124
TI  - Miniature robots can assist in laparoscopic cholecystectomy.
AB  - Laparoscopy reduces patient trauma but eliminates the surgeon's ability to
      directly view and touch the surgical environment. Although current robot-assisted
      laparoscopy improves the surgeon's ability to manipulate and visualize the target
      organs, the instruments and cameras remain constrained by the entry incision.
      This limits tool tip orientation and optimal camera placement. This article
      focuses on developing miniature in vivo robots to assist surgeons during
      laparoscopic surgery by providing an enhanced field of view from multiple angles
      and dexterous manipulators not constrained by the abdominal wall fulcrum effect.
      Miniature camera robots were inserted through a small incision into the
      insufflated abdominal cavity of an anesthetized pig. Trocar insertion and other
      laparoscopic tool placements were then viewed with these robotic cameras. The
      miniature robots provided additional camera angles that improved surgical
      visualization during a cholecystectomy. These successful prototype trials have
      demonstrated that miniature in vivo robots can provide surgeons with additional
      visual information that can increase procedural safety.

PMID- 15742125
TI  - Microsphere intestinal blood flow analysis during pneumoperitoneum using carbon
      dioxide and helium.
AB  - BACKGROUND: Pneumoperitoneum has been associated with a decreased flow in the
      superior mesenteric artery and portal venous system. Intestinal blood flow was
      studied during a 2-h pneumoperitoneum with carbon dioxide (CO2) or helium in a
      porcine model using colored microspheres. METHODS: For this study, 12 pigs were
      divided into two groups (6 CO2 and 6 helium). Different colored microspheres were
      injected directly into the left ventricle before, 40, 80, and 120 min after
      insufflation with either gas at a pressure of 15 mmHg. Microsphere concentration
      was measured in the mucosa and muscularis/serosa layers of the jejunum, cecum,
      and sigmoid colon to calculate blood flow. RESULTS: Intestinal perfusion
      initially increases with insufflation and returns to near baseline levels during
      pneumoperitoneum of 2 h. The effect of helium on tissue perfusion is similar to
      that of carbon dioxide. CONCLUSIONS: Intestinal perfusion does not change
      significantly during prolonged pneumoperitoneum at a pressure of 15 mmHg with CO2
      or helium.

PMID- 15742140
TI  - Development of an automated protein-tyrosine phosphatase 1B inhibition assay and
      the screening of putative insulin-enhancing vanadium(IV) and zinc(II) complexes.
AB  - The inhibition of protein-tyrosine phosphatase 1B (PTP1B) is a potential target
      for treatment of type 2 diabetes. Vanadium and zinc metal coordinated complexes
      have insulin-enhancing activities, and while vanadium compounds inhibit PTP1B,
      little is known on the mode of action of zinc compounds. In this study we
      developed an automated PTP1B inhibition assay that allows for a rapid assessment
      of the PTP1B inhibition strength of candidate compounds. Synthetic vanadium(IV)
      and zinc(II) complexes were evaluated: IC50 values for vanadium complexes ranged
      from 0.06 to 0.8 microM whereas for zinc compounds, values were above 10 microM.
      Vanadium sulfate, a non-conjugated inorganic salt, had stronger inhibition
      activity than any of the conjugated metal complexes.

PMID- 15742141
TI  - Enhancement of the adhesion of fibroblasts by peptide containing an Arg-Gly-Asp
      sequence with poly(ethylene glycol) into a thermo-reversible hydrogel as a
      synthetic extracellular matrix.
AB  - In an effort to regulate the behavior of mammalian cell entrapped in a gel, the
      gels were functionalized with the putative cell-binding (-Arg-Gly-Asp-) (RGD)
      domain. The adhesion molecules composed of Gly-Arg-Gly-Asp-Ser (GRGDS) peptides
      and the cell recognition ligands were inculcated into the thermo-reversible
      hydrogel composed of N-isopropylacrylamide, with a small amount of succinyl
      poly(ethylene glycol) (PEG) acrylate (MW 2000) used as the biomimetic
      extracellular matrix (ECM). The GRGDS-containing p(NiPAAm-co-PEG) copolymer gel
      was examined in vitro for its ability to promote cell spreading and to increase
      the viability of the cells by introducing PEG spacers. ECM poorly adhered to
      hydrogel lacking adhesion molecules permitting only a 20% spread of the seeded
      cells after 10 days. When the PEG spacer arms, which were immobilized by a
      peptide linkage, had been integrated into the hydrogel, the conjugation of RGD
      improved cell spreading by 600% in a 10-day trial.

PMID- 15742142
TI  - In vitro DNA-binding properties of a manganese response regulator (ManR) from
      Anabaena sp.
AB  - ManR of Anabaena sp. PCC 7120 is a manganese response regulator. Two ManR
      molecules bind to the specific DNA sequences at the same time, which was
      demonstrated by our previous results. From size exclusion chromatography, ManR
      exits as monomer in solution. Therefore, cooperative interactions of ManR-ManR
      play a role in DNA binding of the ManR, suggesting that ManR molecules bind co
      operatively to DNA. When serial deletions of N-terminal of the ManR were also
      carried out the mutant proteins, ManRC111, ManRC130 and ManRC158, had completely
      lost the in DNA binding activity. Mutants ManRC 196, ManRC206, ManRC221 and
      ManRC230, however, could specifically bind to DNA, indicating that the amino acid
      residues between Val16 and Ile78 of the N-terminal of ManR are necessary for the
      DNA binding activity of C-terminal domain.

PMID- 15742143
TI  - Thermostable cellulases from Streptomyces sp.: scale-up production in a 50-l
      fermenter.
AB  - Thermostable cellulase was produced by Streptomyces sp. T3-1 grown in a 50-l
      fermenter. Maximum cellulase activity was attained on the fourth day when
      agitation speeds and aeration rates were controlled at 300 rpm and 0.75 vvm,
      respectively. Maximum enzyme activities were: 148 IU CMCase ml(-1), 45 IU
      Avicelase ml(-1), and 137 IU beta-glucosidase ml(-1) with productivity of 326 IU
      l(-1) h(-1), which were 10-32% higher than the values obtained in shake-flask
      cultures.

PMID- 15742144
TI  - Use of plant protein hydrolysates for varicella virus production in serum-free
      medium.
AB  - Serum-free media containing no animal-derived components were assessed for their
      efficacy to produce live attenuated varicella virus. Serum-free medium containing
      an ultrafiltrate of soy protein acid hydrolysate and lipid resulted in a viral
      production yield comparable to media containing fetal bovine serum, indicating
      that varicella virus can be produced without the risk of contamination associated
      with the use of bovine serum.

PMID- 15742145
TI  - Survival of Lactobacillus sakei during heating, drying and storage in the dried
      state when growth has occurred in the presence of sucrose or monosodium
      glutamate.
AB  - Spray-dried cells of Lactobacillus sakei CTC 494 survived ca. 60% longer in the
      spray dried state when cells were grown in the presence of 20 g sucrose l(-1) or
      12.5 g monosodium glutamate l(-1). No significant differences were observed in
      viability during storage in the freeze dried state with the addition of these
      compounds to the growth medium, nor in survival during a heat treatment (55
      degrees C). Both sucrose and glutamate in the growth medium suppressed
      intracellular accumulation of total amino acids and changed the overall pattern
      of the individual amino acids. Glutamate in the growth medium enhanced
      intracellular glutamate by ca. 38%.

PMID- 15742146
TI  - A carbohydrate fraction, AIP1, from Artemisia iwayomogi down-regulates Fas gene
      expression and suppresses apoptotic death of the thymocytes induced by 2,3,7,8
      tectrachlorodibenzo-p-dioxin.
AB  - Apoptotic death of mouse thymocytes in vitro, as induced by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), involves the up-regulation of Fas gene
      expression, while a carbohydrate fraction, AIP1, from Artemisia iwayomogi
      suppresses the death of thymocytes in culture along with the down-regulation of
      Fas gene expression. We have now investigated whether the AIP1 fraction modulates
      TCDD-induced thymocyte death. When treated with TCDD and AIP1 fraction together,
      the thymocytes do not show apoptosis induced by the TCDD treatment. The AIP1
      supplementation to the TCDD treatment also down-regulates the TCDD-induced Fas
      gene up-regulation. These findings indicate that the AIP1 fraction suppresses
      TCDD-induced thymocyte apoptosis through the modulation of Fas gene expression.

PMID- 15742147
TI  - Ethanol production from cellulosic materials by genetically engineered Zymomonas
      mobilis.
AB  - To confer the ability to ferment cello-oligosaccharides on the ethanol-producing
      bacterium, Zymomonas mobilis, the beta-glucosidase gene from Ruminococcus albus,
      tagged at its N-terminal with the 53-amino acid Tat signal peptide from the
      periplasmic enzyme glucose-fructose oxidoreductase from Z. mobilis, was
      introduced into the strain. The tag enabled 61% of the beta-glucosidase activity
      to be transported through the cytoplasmic membrane of the recombinant strain
      which then produced 0.49 g ethanol/g cellobiose.

PMID- 15742148
TI  - Enhancement of photorespiration in immobilized Chlamydomonas reinhardtii cells.
AB  - Immobilization of Chlamydomonas reinhardtii in alginate increases its
      photorespiration rate. In the immobilized cells, the photorespiratory enzyme,
      phosphoglycolate phosphatase, was 75% higher than in freely suspended cells.
      Thus, the immobilized cells produced glycolate at twice the rate than in freely
      suspended cells when treated with aminooxyacetate (a transaminase inhibitor).
      With immobilized cells in a batch reactor, 270 micromol glycolate mg(-1) Chl was
      produced after 12 h.

PMID- 15742149
TI  - Optimization of theaflavin biosynthesis from tea polyphenols using an immobilized
      enzyme system and response surface methodology.
AB  - Theaflavins were synthesized from tea polyphenols extracted from green tea using
      an immobilized polyphenol oxidase system. To optimize the production of
      theaflavins, response surface methodology was applied to determine the effects of
      five critical variables and their mutual interactions on theaflavin biosynthesis
      at five levels. A total of 52 individual experiments were performed and a
      statistical model predicted that the highest theaflavin concentration was 0.766
      mg ml(-1) at optimized conditions. Using these optimal parameters under
      experimental conditions in three independent replicates, the average value of the
      biosynthesized theaflavin concentration reached 0.75 +/- 0.017 mg ml(-1) and
      matched the value predicted by the model.

PMID- 15742150
TI  - A new isolate of Pseudomonas stutzerithat degrades 2-chloronitrobenzene.
AB  - A strain of Pseudomonas stutzeri ZWLR2-1 was isolated from soil contaminated with
      chloronitrobenzenes and identified by 16S rDNA sequencing. This bacterium
      released chloride and nitrite into the medium when grown on 0.5 mM 2
      chloronitrobenzene. PCR amplification and DNA sequencing revealed a DNA fragment
      encoding a polypeptide homologous to the alpha-subunit of ring-hydroxylating
      dioxygenases.

PMID- 15742151
TI  - Nitrogen-dependent regulation of medium-chain length polyhydroxyalkanoate
      biosynthesis genes in pseudomonads.
AB  - Comparative transcriptional analysis of polyhdroxyalkanoate (PHA) biosynthesis
      genes with wild type strains and mutants, which lack the intact alternative sigma
      factor gene rpoN, was performed using semi-quantitative RT-PCR. In Pseudomonas
      putida and Pseudomonas aeruginosa, phaI and phaF were co-transcribed. PhaF was a
      negative regulator of transcription of PHA synthase gene phaC1 but did not serve
      as auto-repressor. However, the alternative sigma factor RpoN is suggested as
      negative regulator of phaF transcription. In P. putida, phaI-phaF transcription
      is strongly dependent on nitrogen availability and PHA accumulation, whereas phaF
      transcription is not. These data suggested a differential regulation of phaF and
      phaIF. The phaC1 gene transcription occurred almost independently by of RpoN or
      nitrogen availability in both pseudomonads.

PMID- 15742154
TI  - The inhibitory co-receptor, PECAM-1 provides a protective effect in suppression
      of collagen-induced arthritis.
AB  - Studies of PECAM-1(-/-) mice have identified that PECAM-1 functions as an
      inhibitory co-receptor to modulate immunological responsiveness. In this study,
      we describe the in vivo consequences of PECAM-1 deficiency in mouse models of
      collagen-induced arthritis (CIA) and K/BxN passive transfer model that resembles
      many of the features of human rheumatoid arthritis. Immunization of PECAM-1(-/-)
      C57BL/6 (H-2b) mice with chicken collagen type II induced CIA with an incidence
      of 82% by day 49, while 33%; of wild-type and 100% of DBA/1 mice developed
      arthritis in a similar time frame. The mean onset of disease for PECAM-1(-/-)
      C57BL/6 mice was day 32 compared to day 51 for wild-type C57BL/6 mice and day 18
      for DBA/1 mice (H-2q susceptible). In terms of disease severity, the mean maximal
      arthritic index for PECAM-1(-/-) C57BL/6 mice was comparable to DBA/1 mice (8.91
      +/- 0.91 vs 11.67 +/- 0.82). This mean maximal index in PECAM-1(-/-) C57BL/6 mice
      was significantly higher than wild-type C57BL/6 mice (5.00 +/- 0.73). IgG1 and
      IgG2b antibody responses against CII were elevated in arthritic PECAM-1(-/-)
      C57BL/6 mice compared to wild-type C57BL/6 mice. Histological examination of
      arthritic paws of PECAM-1(-/-) C57BL/6 mice revealed inflammatory infiltrates of
      lymphocytic/monocytic cells and cartilage/bone destruction similar to CIA-induced
      DBA/1 arthritic paws. In the K/BxN model, the arthritis was not augmented in
      PECAM-1(-/-) mice compared to wild-type mice. In contrast, in active CIA, PECAM
      1(-/-) mice developed severe disease comparable to susceptible DBA/1 mice and
      profoundly more severe than C57BL/6 mice, where only one third developed a
      mild/moderate disease. Together these observations suggest that PECAM-1 plays a
      crucial role in the suppression of development of autoimmune arthritis.

PMID- 15742153
TI  - Fc receptors and their role in immune regulation and autoimmunity.
AB  - The activation threshold of cells in the immune system is often tuned by cell
      surface molecules. The Fc receptors expressed on various hematopoietic cells
      constitute critical elements for activating or downmodulating immune responses
      and combines humoral and cell-mediated immunity. Thus, Fc receptors are the
      intelligent sensors of the immune status in the individual. However, impaired
      regulation by Fc receptors will lead to unresponsiveness or hyperreactivity to
      foreign as well as self-antigens. Murine models for autoimmune disease indicate
      the indispensable roles of the inhibitory Fc receptor in the suppression of such
      disorders, whereas activating-type FcRs are crucial for the onset and
      exacerbation of the disease. The development of many autoimmune diseases in
      humans may be caused by impairment of the human Fc receptor regulatory system.
      This review is aimed at providing a current overview of the mechanism of Fc
      receptor-based immune regulation and the possible scenario of how autoimmune
      disease might result from their dysfunction.

PMID- 15742156
TI  - Expression of the CD7 ligand K-12 in human thymic epithelial cells: regulation by
      IFN-gamma.
AB  - CD7 is an immunoglobulin superfamily molecule expressed on T, NK, and pre-B
      lymphocytes. Previous studies have demonstrated a role for CD7 in T- and NK-cell
      activation and cytokine production. Recently, an epithelial cell secreted
      protein, K12, was identified as a CD7 ligand. Although CD7 is expressed
      intrathymically, it is not known if K12 is produced in human thymus. To determine
      roles that K12 might play in the human thymus, we analyzed expression of K12 in
      human thymocytes, thymic epithelial cells (TE), and thymic fibroblasts. We found
      that recombinant human K12 bound strongly to soluble hCD7, with a Keq of 37.6x10(
      9) M, and this interaction was inhibited by a novel antihuman K12 monoclonal
      antibody (K12-A1). K12 mRNA was detected by RT-PCR and northern analysis in human
      TE and thymic fibroblasts, but not in human thymocytes. Expression of K12 in TE
      cells was upregulated by IFN-gamma. Taken together, these data demonstrated that
      K12 is produced by human TE cells and thymic fibroblasts, and is regulated in
      thymus by IFN-gamma. These data suggest a role for thymic microenvironment
      produced K12 in regulation of thymocyte signaling and cytokine release,
      particularly in the setting of thymus pathology where IFN-gamma is upregulated
      such as myasthenia gravis.

PMID- 15742155
TI  - TLR-9 activation of marginal zone B cells in lupus mice regulates immunity
      through increased IL-10 production.
AB  - Bacterial DNA triggers B-cell proliferation and induces immunoglobulin secretion.
      Chromatin-IgG complexes activate autoreactive B cells by co-engaging B-cell
      receptor (BCR) and TLR-9, thus suggesting a role for innate signaling in systemic
      autoimmunity. Spleen cells from lupus prone Palmerston North (PN) mice produce
      several fold less IL-12p40 than controls in response to CpG-oligodeoxynucleotides
      (ODNs). Here we show that B cells are primarily responsible for this abnormality.
      The removal of B cells from PN cultures markedly increased IL-12p40. Moreover,
      the addition of purified B cells back to PN splenocyte cultures resulted in a B
      cell number dependent/ IL-10-mediated suppression of IL-12p40. The B cells were
      the major source of IL-10. In response to CpG, B cells from several lupus strains
      produced twice as a much IL-10 as controls, but failed to produce IL-10 when
      stimulated through BCR or CD40. PN and control mice expressed IL-10R similarly,
      and the difference in IL-10 secretion remained when anti-IL-10R blocking
      antibodies were used. IFN-gamma and IL-4 regulated CpG-induced IL-10 secretion in
      opposite directions. The abnormal IL-10 response in lupus mice was derived from B
      cells with the marginal zone phenotype, and could be downregulated with
      inhibitory ODNs. We hypothesize that TLR-9 activated lupus B cells can modulate T
      cell mediated inflammatory responses through IL-10 production. Therefore, B cells
      may contribute to the lupus pathogenesis in many different ways: as antigen
      presenting cells for self antigens, as effector cells for autoantibody
      production, and as IL-10 secreting regulatory cells.

PMID- 15742157
TI  - Long-term effects of IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells on
      immune response in Lewis rats.
AB  - Increasing data have shown that IFN-gamma, IL-10, and TGF-beta-modulated
      dendritic cells (DC) provide a promising strategy in treatment of experimental
      allergic encephalomyelitis and experimental autoimmune myasthenia gravis through
      different manner. To explore the immune response status after long-term
      application of these cytokine-modulated-DC, Lewis rats were injected
      subcutaneously into naive DC and IFN-gamma, IL-10, and TGF-beta-modulated DC
      (i.e., IFN-gamma-DC, IL-10-DC, and TGF-beta-DC) at does of 1 x 10(6) cells/rat
      every month for continuous 18 months, respectively. No rats suffered from
      decreased vigor and activity as well as cachectic condition during 18-month
      observation, and no rats had body-weight loss after 18-month treatment.
      Exploratory laparectomy did not find any tumor in all rats. IL-10-DC and TGF-beta
      DC resulted in lower nonspecific (Con A-induced) and antigen specific (ovalbumin
      stimulated) spleen mononuclear cells proliferation, accompanied by lower levels
      of IFN-gamma, IL-10, and TNF-alpha. On the contrary, IFN-gamma-DC did not
      suppress cell proliferation and IFN-gamma and IL-10 production except only
      slightly decreased TNF-alpha levels. These results suggest that IFN-gamma-DC
      seems to be a more ideal candidate in the treatment of autoimmune diseases
      without suppressing immune response.

PMID- 15742158
TI  - Not all tetramer binding CD8+ T cells can produce cytokines and chemokines
      involved in the effector functions of virus-specific CD8+ T lymphocytes in HIV-1
      infected children.
AB  - In the pediatric human immunodeficiency virus type-1 (HIV-1) infection, the
      presence of cytotoxic T lymphocytes (CTL) is associated with a slow progression
      to AIDS. The secretion of cytokines by CTLs may be critical in the control of
      viral infection. We used the combination of cell surface and intracellular
      staining to study the functionality of tetramer binding CD8+ T cells recognizing
      two HIV-1 immunodominant epitopes, in peripheral blood mononuclear cells from HIV
      1-infected children. A fraction of tetramer positive CD8+ T cells produce
      cytokines (IFN-gamma, TNF-alpha) or chemokines (CCL4, CCL5) after ex vivo
      stimulation with the cognate peptide. There was a negative correlation between
      the plasma viral load and the percentage of CD8+ Tetramer Gag+ T cells secreting
      IFN-gamma. This is the first report in the context of pediatric HIV-1 infection
      showing that only a fraction of HIV-1-specific CD8+ T cells have the capacity to
      produce cytokines and chemokines implicated in their antiviral functions.

PMID- 15742159
TI  - Activation and coreceptor expression of T lymphocytes in HIV/AIDS patients of
      China.
AB  - The objective of this paper was to investigate the activation and coreceptor
      CCR5, CXCR4 expression of T lymphocytes in HIV/AIDS patients of China, and to
      study their association with disease progression. Seventy-seven HIV/AIDS patients
      and thirteen normal controls were enrolled and three-color flow-cytometry was
      used to detect the activation marker HLA-DR, CD38 and the coreceptor CCR5, CXCR4
      expression on T lymphocytes in whole blood samples taken from the patients and
      the controls. The HLA-DR, CD38 and CCR5 expression on CD4, CD8+ T cells in AIDS
      patients was higher than in asymptomatic HIV-1 infected patients and normal
      controls (p < 0.05); The activation and CCR5 expression on T lymphocytes
      significantly correlated with CD4+ T lymphocyte number and viral load. The
      activation on T lymphocytes and the expression of CCR5 on T lymphocytes in
      HIV/AIDS patients of China are significantly correlated with disease progression.

PMID- 15742160
TI  - Primary immunodeficiency disorders in the Republic of Ireland: first report of
      the national registry in children and adults.
AB  - Data collection for the national registry for patients with primary
      immunodeficiency disorders in the Republic of Ireland commenced in 1996. One
      hundred and fifteen cases of primary immunodeficiency diseases were registered
      between December 1996 and February 2003. The most frequent primary
      immunodeficiency disorders were antibody deficiency (n = 53) and complement
      deficiency (n = 32). In addition, patients with T cell deficiency (n = 11) and
      chronic granulomatous disease (n = 11) were identified. A small number of
      patients with Wiskott-Aldrich syndrome, natural killer cell deficiency, DiGeorge
      syndrome and chronic mucocutaneous candidiasis were also registered. Comparison
      of our data with that recently reported in the European registry revealed that
      complement deficiency was more prevalent in the Republic of Ireland compared to
      other European countries. Results of our registry point to a significant
      prevalence of primary immunodeficiency disorders in the Republic of Ireland (2.9
      cases per 100,000 population). However, it is likely that these figures
      underestimate the true prevalence of such cases in the country. We hope, with
      increased awareness of the national registry among primary care physicians, that
      more patients will be included and we will be able to identify accurately the
      frequency and the distribution of these disorders.

PMID- 15742161
TI  - Immunological status in the aetiology of recurrent otitis media with effusion:
      serum immunoglobulin levels, functional mannose-binding lectin and Fc receptor
      polymorphisms for IgG.
AB  - The objective was to study the role of serum immunoglobulin levels, mannose
      binding lectin (MBL), and Fc gamma receptor (FcgammaR) polymorphisms on the
      development of recurrent otitis media with effusion (OME). Children aged between
      two and seven years with persisting OME received bilateral tympanostomy tubes and
      immunological parameters were investigated in relation with OME recurrence within
      six months after tube extrusion. No statistically significant differences in
      serum immunoglobulin levels were present between children with and without OME
      recurrence. In children with bilateral recurrence (n = 56), median levels of MBL
      were 1.39 mg/L compared to 2.48 mg/L in children with OME recurrence (n = 17) (p
      = 0.29). In addition, 34% of the children with bilateral recurrence were
      homozygous for the genotype FcgammaRIIa-R/R131, whereas less than 20% of the
      children with unilateral recurrence or those without recurrence were homozygous
      for this Fcgamma receptor (p = 0.26). Serum mannose-binding lectin and
      FcgammaRIIa-R/R131 polymorphism may play a role in the aetio-pathogenesis of
      recurrent OME.

PMID- 15742162
TI  - Chimpanzee (Pan troglodytes) intentional communication is not contingent upon
      food.
AB  - Studies of great apes have revealed that they use manual gestures and other
      signals to communicate about distal objects. There is also evidence that
      chimpanzees modify the types of communicative signals they use depending on the
      attentional state of a human communicative partner. The majority of previous
      studies have involved chimpanzees requesting food items from a human
      experimenter. Here, these same communicative behaviors are reported in
      chimpanzees requesting a tool from a human observer. In this study, captive
      chimpanzees were found to gesture, vocalize, and display more often when the
      experimenter had a tool than when she did not. It was also found that chimpanzees
      responded differentially based on the attentional state of a human experimenter,
      and when given the wrong tool persisted in their communicative efforts.
      Implications for the referential and intentional nature of chimpanzee
      communicative signaling are discussed.

PMID- 15742163
TI  - [Early diagnosis in internal medicine].

PMID- 15742164
TI  - [Early diagnosis of chronic kidney diseases].
AB  - Chronic kidney diseases frequently progress to end-stage renal failure over a
      period of several years. Ultimately, the glomerular filtration apparatus and
      tubulus are destroyed to such an extent that renal replacement therapy is
      required. This process may last longer than 10 years. To avoid loss of renal
      function, chronic kidney diseases should be diagnosed as early as possible so
      that therapeutic measures are initiated in time. Medications which prevent or
      delay progression to end-stage renal failure, e.g. ACE inhibitors and AT(1)
      blockers, are more effective if started early in the course of renal disease. A
      significant number of patients with chronic kidney disease are still diagnosed
      too late and are without adequate therapy so that chances for prevention and/or
      delay of chronic kidney disease are missed.

PMID- 15742165
TI  - [Why is it nobody understands me, yet everybody likes me? 50th anniversary of the
      death of Albert Einstein (1879-1955)].

PMID- 15742166
TI  - Involvement of fengycin-type lipopeptides in the multifaceted biocontrol
      potential of Bacillus subtilis.
AB  - In this work, the potential of Bacillus subtilis strain M4 at protecting plants
      against fungal diseases was demonstrated in different pathosystems. We provide
      evidence for the role of secreted lipopeptides, and more particularly of
      fengycins, in the protective effect afforded by the strain against damping-off of
      bean seedlings caused by Pythium ultimum and against gray mold of apple in post
      harvest disease. This role was demonstrated by the strong biocontrol activity of
      lipopeptide-enriched extracts and through the detection of inhibitory quantities
      of fengycins in infected tissues. Beside such a direct antagonism of the
      pathogen, we show that root pre-inoculation with M4 enabled the host plant to
      react more efficiently to subsequent pathogen infection on leaves. Fengycins
      could also be involved in this systemic resistance-eliciting effect of strain M4,
      as these molecules may induce the synthesis of plant phenolics involved in or
      derived from the defense-related phenylpropanoid metabolism. Much remains to be
      discovered about the mechanisms by which Bacillus spp suppress disease. Through
      this study on strain M4, we reinforce the interest in B. subtilis as a pathogen
      antagonist and plant defense-inducing agent. The secretion of cyclic fengycin
      type lipopeptides may be tightly related to the expression of these two
      biocontrol traits.

PMID- 15742167
TI  - Phenol and 2-naphthol production by toluene 4-monooxygenases using an
      aqueous/dioctyl phthalate system.
AB  - A two-phase system is developed here for converting: (1) benzene to phenol and
      (2) naphthalene to 2-naphthol, using whole cells expressing wild-type toluene 4
      monooxygenase (T4MO) and the alpha subunit variant TmoA I100A from Pseudomonas
      mendocina KR1. Using the T4MO TmoA I100A variant, the solubility of naphthalene
      was enhanced and the toxicity of the naphthols was prevented by the use of a
      water/dioctyl phthalate (80:20, vol%) system which yielded 21-fold more 2
      naphthol. More than 99% 2-naphthol was extracted to the dioctyl phthalate phase,
      dihydroxynaphthalene formation was prevented, 92% 2-naphthol was formed, and 12%
      naphthalene was converted. Similarly, using 50 vol% dioctyl phthalate, an initial
      concentration of 3.0 g l(-1) (39 mM), and wild-type T4MO, a 51+/-9% conversion of
      benzene was obtained and phenol was produced at a purity of 97%. Relative to the
      one-phase system, there was a 12-fold reduction in the formation of the byproduct
      catechol.

PMID- 15742168
TI  - Genetically engineered termite gut bacteria (Enterobacter cloacae) deliver and
      spread foreign genes in termite colonies.
AB  - Indigenous gut bacteria of the Formosan subterranean termite (Coptotermes
      formosanus Shiraki, Isoptera: Rhinotermitidae) were used as shuttle systems to
      deliver, express and spread foreign genes in termite colonies. The gut bacterium
      Enterobacter cloacae was transformed with a recombinant plasmid (pEGFP)
      containing genes encoding ampicillin resistance and green fluorescent protein
      (GFP). In laboratory experiments, termite workers and soldiers from three
      colonies were fed with filter paper inoculated with transformed bacteria.
      Transformed bacteria were detected in termite guts by growing the entire gut
      flora under selective conditions and checking the cultures visually for
      fluorescence. We demonstrated that (1) transformed bacteria were ingested within
      a few hours and the GFP gene was expressed in the termite gut; (2) transformed
      bacteria established a persistent population in the termite gut for up to 11
      weeks; (3) transformed bacteria were efficiently transferred throughout a
      laboratory colony, even when the donor (termites initially fed with transformed
      bacteria) to recipient (not fed) ratio was low; (4) transformed E. cloacae were
      transferred into soil; however, they did not accumulate over time and the GFP
      plasmid was not transferred to other soil bacteria. In the future, transgenic
      bacteria may be used to shuttle detrimental genes into termite colonies for
      improved pest control.

PMID- 15742169
TI  - Nutcracker or left renal vein compression phenomenon: multidetector computed
      tomography findings and clinical significance.
AB  - The use of multidetector computed tomography (MDCT) in routine abdominal
      explorations has increased the detection of the nutcracker phenomenon, defined as
      left renal vein (LRV) compression by adjacent anatomic structures. The embryology
      and anatomy of the nutcracker phenomenon are relevant as a background for the
      nutcracker syndrome, a rare cause of hematuria as well as other symptoms. MDCT
      examples of collateral renal vein circulation (gonadal, ureteric, azygous,
      lumbar, capsular) and aortomesenteric (anterior) and retroaortic (posterior)
      nutcracker phenomena in patients with no urologic complaint are shown as well as
      studies performed on patients with gross hematuria of uncertain origin.
      Incidental observation of collateral veins draining the LRV in abdominal MDCT
      explorations of asymptomatic patients may be a sign of a compensating nutcracker
      phenomenon. Imbalance between LRV compression and development of collateral
      circulation may lead to symptomatic nutcracker syndrome.

PMID- 15742170
TI  - Clinical, histological and molecular follow-up of 60 patients with gastric
      marginal zone lymphoma of mucosa-associated lymphoid tissue.
AB  - The persistence of gastric lymphoma after Helicobacter pylori eradication may be
      difficult to evidence on endoscopic and histological examination. The aims of the
      study were to evaluate the detection of monoclonal immunoglobulin H (IgH) gene
      rearrangement in endoscopically infiltrated and normal mucosa at diagnosis and
      during follow-up in order to determine its clinical and prognostic impact. We
      studied 60 gastric marginal zone lymphomas of mucosa-associated lymphoid tissue
      (MALT), and IgH monoclonality was detected at diagnosis in 52 patients (87%). The
      endoscopically normal mucosa contained clonal lymphomatous cells in 69% of cases
      before remission. A complete histological remission (HR) was observed in 28
      patients (47%). Among them, 23 were followed for molecular remission (MR). The
      median delay was 10 months to achieve HR and 18 months to achieve MR.
      Interestingly, patients with HR but not MR had a longer delay to achieve HR (21
      months) (P=0.0006) and a more frequent clonal normal mucosa at diagnosis (88%)
      than patients with both HR and MR (10 months and 39%, respectively). The presence
      of monoclonal B cells at both infiltrated and normal sites may therefore identify
      patients with a longer delay to achieve complete response, suggesting that
      molecular dissemination may require therapeutic intensification.

PMID- 15742171
TI  - Resistance of multidrug-resistant strains of Mycobacterium tuberculosis from the
      Archangel oblast, Russia, to second-line anti-tuberculosis drugs.
AB  - Multidrug-resistant tuberculosis has become common all over the world,
      necessitating the inclusion of second-line drugs in treatment regimens. In the
      present study, the susceptibility of a selection of multidrug-resistant strains
      of Mycobacterium tuberculosis isolated in the Archangel oblast, Russia, to second
      line anti-tuberculosis drugs was analysed. Susceptibility testing of 77
      Mycobacterium tuberculosis strains was performed by the Bactec method using the
      following recommended drug concentrations: capreomycin 1.25 microg/ml;
      ethionamide 1.25 microg/ml; kanamycin 5 microg/ml; and ofloxacin 2 microg/ml. The
      majority of strains (92.2%) were resistant to ethionamide. High rates of drug
      resistance were also found for capreomycin (42.9%) and kanamycin (41.6%), while
      nearly all strains (98.7%) were susceptible to ofloxacin. The high rates of
      resistance to ethionamide, capreomycin, and kanamycin show the real burden of
      drug resistance in the region and pose a serious problem for the treatment of
      patients with multidrug-resistant tuberculosis.

PMID- 15742172
TI  - [Nitrous oxide].

PMID- 15742174
TI  - Clinical value of pulse pressure variations in ARDS. Still an unresolved issue?

PMID- 15742173
TI  - [Controlled mild-to-moderate hypothermia in the intensive care unit].
AB  - Controlled hypothermia is used as a therapeutic intervention to provide
      neuroprotection and (more recently) cardioprotection. The growing insight into
      the underlying pathophysiology of apoptosis and destructive processes at the
      cellular level, and the mechanisms underlying the protective effects of
      hypothermia, have led to improved application and to a widening of the range of
      potential indications. In many centres hypothermia has now become part of the
      standard therapy for post-anoxic coma in certain patients, but for other
      indications its use still remains controversial. The negative findings of some
      studies may be partly explained by inadequate protocols for the application of
      hypothermia and insufficient attention to the prevention of potential side
      effects. This review deals with some of the concepts underlying hypothermia
      associated neuroprotection and cardioprotection, and discusses some potential
      clinical indications as well as reasons why some clinical trials may have
      produced conflicting results. Practical aspects such as methods to induce
      hypothermia, as well as the side effects of cooling are also discussed.

PMID- 15742176
TI  - Regulations of education and training of intensive care medicine in Germany and
      their structural consequences.

PMID- 15742175
TI  - Noninvasive ventilation in hypercapnic acute respiratory failure due to chronic
      obstructive pulmonary disease vs. other conditions: effectiveness and predictors
      of failure.
AB  - OBJECTIVE: This study compared the effectiveness of noninvasive ventilation (NIV)
      and the risk factors for NIV failure in hypercapnic acute respiratory failure
      (ARF) due to chronic obstructive pulmonary disease (COPD) vs. non-COPD
      conditions. DESIGN AND SETTING: Prospective cohort study in the medical intensive
      care unit of a university hospital. PATIENTS AND PARTICIPANTS: 111 patients with
      hypercapnic ARF, 43 of whom had COPD exacerbations and 68 other conditions.
      Baseline characteristics of the two groups were similar. MEASUREMENTS AND
      RESULTS: The risk of NIV failure, defined as the need for endotracheal
      intubation, was significantly lower in COPD than in other conditions (19% vs.
      47%). High APACHE II score was an independent predictor of NIV failure in COPD
      (OR 5.38 per 5 points). The presence of pneumonia (OR 5.63), high APACHE II score
      (OR 2.59 per 5 points), rapid heart rate (OR 1.22 per 5 beats/min), and high
      PaCO(2) 1 h after NIV (OR 1.22 per 5 mmHg) were independent predictors of NIV
      failure in the non-COPD group. Failure of NIV independently predicted mortality
      (OR 10.53). CONCLUSIONS: Noninvasive ventilation was more effective in preventing
      endotracheal intubation in hypercapnic ARF due to COPD than non-COPD conditions.
      High APACHE II score predicted NIV failure in both groups. Noninvasive
      ventilation was least effective in patients with hypercapnic ARF due to
      pneumonia.

PMID- 15742178
TI  - Growth hormone abuse and bodybuilding as aetiological factors in the development
      of bilateral internal laryngocoeles. A case report.
AB  - A 36-year-old man presented with hoarseness and stridor. He was an elite
      professional bodybuilder and admitted to having abusing anabolic steroids and
      growth hormone in the recent past. A CT scan showed bilateral laryngocoeles. The
      patient was initially managed with intravenous corticosteroids and broad-spectrum
      antibiotics, and the stridor resolved sufficiently to permit discharge from the
      hospital. He proceeded to undergo endoscopic marsupialisation of his
      laryngocoeles and to date has made a full recovery. This is the first reported
      case where anabolic steroid and growth hormone abuse combined with an elite
      bodybuilder's exercise regime has been implicated in the aetiology of bilateral
      laryngocoeles.

PMID- 15742177
TI  - The protective effect of erdosteine against ototoxicity induced by cisplatin in
      rats.
AB  - The elimination of cisplatin ototoxicity is an ongoing concern. This experimental
      study was undertaken to investigate the effect of oral erdosteine in ameliorating
      cisplatin-induced ototoxicity. Twenty-eight adult female Wistar albino rats were
      randomly divided into four equal groups. Group A received an oral carrier vehicle
      of the drug erdosteine with 0.2 ml of 0.9% saline. Group B was administered only
      erdosteine (per oral 10 mg/kg twice a day) for 6 days. Group C was injected with
      cisplatin intraperitoneally (i.p.) on day 0 (16 mg/kg body weight), once only.
      Group D was given erdosteine (per oral 10 mg/kg/day) 1 day before and for 5 days
      consecutively after cisplatin injection (16 mg/kg, i.p.). Distortion product
      otoacoustic emissions (DPOAEs) were elicited in different frequency regions,
      ranging from 1,001 to 6,299 Hz as DPgram and input/output (I/O) functions from
      the control and experimental animals. All experimental animals were killed under
      general anesthesia on day 5, following the last otoacoustic emission
      measurements. Prior to death, blood samples were drawn for measurement of
      superoxide dismutase, xanthine oxidase (XO), malondialdehyde and nitric oxide.
      Initial DPgram and I/O function baseline measurements were similar in all groups
      prior to any drug administration ( P>0.05). On day 5, intra-subject measurement
      parameters of DPgrams and I/O functions in the cisplatin group showed significant
      deterioration ( P <0.05). The other groups revealed no differences between their
      pre- and post-test drug administration DPgrams and I/O functions at any test
      frequency ( P>0.05). Comparison of the amplitudes of DPgrams and I/O functions
      between the cisplatin and control groups showed significant changes ( P <0.05).
      Biochemical studies noted an increased XO activity following cisplatin
      administration ( P <0.007). The other biochemical results did not show
      significant differences between the study and control groups. This study
      demonstrates that, in rats, erdosteine is protective for cochlear function
      against the disruptive effects of cisplatin as measured by DPOAEs.

PMID- 15742179
TI  - Cervical emphysema, pneumomediastinum, and retropneumoperitoneum following
      sigmoidoscopy and rectal biopsy.

PMID- 15742181
TI  - Solution to spectroscopy challenge 8.

PMID- 15742182
TI  - Paradigms, tunnel vision, and group thinking.

PMID- 15742180
TI  - NHERF and regulation of the renal sodium-hydrogen exchanger NHE3.
AB  - The sodium-hydrogen exchanger 3 (NHE3) isoform is the major regulated sodium
      transporter in the proximal convoluted tubule of the kidney. Study of the
      regulation of NHE3 by hormonal stimuli has identified a number of PDZ adaptor
      proteins that form an apical/subapical membrane scaffold that binds NHE3 and
      facilitates down-regulation of its activity in response to cAMP and activation of
      protein kinase A. The precise relation of proximal tubule adaptor proteins such
      as sodium-hydrogen exchanger regulatory factor-1 (NHERF-1), NHERF-2, and PDZ
      domain-containing-protein-1 (PDZK1) with each other and with protein targets such
      as NHE3 has been evolving with the development of specific reagents and
      genetically altered animals. In this review, we trace the discovery of NHERF-1
      and NHERF-2, and update our current understanding of the relation between these
      proteins and the regulation and trafficking of NHE3.

PMID- 15742183
TI  - A novel amperometric sensor and chromatographic detector for determination of
      parathion.
AB  - A novel amperometric sensor and chromatographic detector for determination of
      parathion has been fabricated from a multi-wall carbon nano-tube (MWCNT)/Nafion
      film-modified glassy-carbon electrode (GCE). The electrochemical response to
      parathion at the MWCNT/Nafion film electrode was investigated by cyclic
      voltammetry and linear sweep voltammetry. The redox current of parathion at the
      MWCNT/Nafion film electrode was significantly higher than that at the bare GCE,
      the MWCNT-modified GCE, and the Nafion-modified GCE. The results indicated that
      the MWCNT/Nafion film had an efficient electrocatalytic effect on the
      electrochemical response to parathion. The peak current was proportional to the
      concentration of parathion in the range 5.0x10(-9)-2.0x10(-5) mol L(-1). The
      detection limit was 1.0x10(-9) mol L(-1) (after 120 s accumulation). In high
      performance liquid chromatography with electrochemical detection (HPLC-ED) a
      stable and sensitive current response was obtained for parathion at the
      MWCNT/Nafion film electrode. The linear range for parathion was over four orders
      of magnitude and the detection limit was 6.0x10(-9) mol L(-1). Application of the
      method for determination of parathion in rice was satisfactory.

PMID- 15742184
TI  - [Voice Handicap Index (VHI) in inpatient voice rehabilitation medicine].
AB  - BACKGROUND: The focus of this study was to determine if the Voice Handicap Index
      (VHI) is a valid tool for evaluating an inpatient voice rehabilitation program.
      PATIENTS AND METHODS: A total of 39 German-speaking patients were asked to
      complete a German version of the VHI questionnaire at the beginning and 3 months
      after attending a voice rehabilitation program on an inpatient basis at the Bad
      Gogging voice center. The data collected were documented and assessed using
      Microsoft Excel and MATLAB. RESULTS: A significant reduction of the VHI summary
      score was achieved by 10 of 39 patients. An increased number of voice therapy
      sessions before the program diminished (!) the VHI score 3 months after the
      program. Work disability because of the dysphonia before the beginning of the
      voice rehabilitation program showed no significant correlation with the VHI
      score. CONCLUSIONS: At present, the VHI cannot be regarded as a reliable measure
      to evaluate benefit derived from completing a voice rehabilitation program on an
      inpatient basis. Apparently, numerous prior treatment regimens constitute a
      negative prognostic criterion for rehabilitation success as measured subjectively
      by the VHI.

PMID- 15742185
TI  - Vertebral osteomyelitis in an infant presenting with pseudotumor and narrowing of
      the spinal canal.
AB  - In an 8-week-old infant, kyphosis caused by destruction of the 7th thoracic
      vertebra was observed. A paraspinal mass and narrowing of the spinal canal due to
      vertebral osteomyelitis were present. Treatment with antibiotics and bracing was
      carried out with no evidence of neurologic disturbances over a follow-up period
      of 24 months.

PMID- 15742186
TI  - Benign breast lesions in adolescent girls: an overview with a case report.
AB  - A wide spectrum of breast disorders occurs in the paediatric and adolescent age
      groups, but malignant disease is very rare. The relative frequencies of these
      conditions and their natural history differ substantially from those of adult
      patients. The gross findings may be very deceptive and mislead the clinician
      until a histopathological diagnosis is made. We report a case in an adolescent
      girl that was initially diagnosed and treated as fibroadenoma until a
      histological assessment proved it to be a phyllodes tumour with malignant
      potential.

PMID- 15742187
TI  - The protective effect of selenium on ipsilateral and contralateral testes in
      testicular reperfusion injury.
AB  - This study was designed to investigate the effect of selenium on ipsilateral and
      contralateral testicular damage after unilateral testicular torsion/detorsion
      (T/D). Thirty-two male rats were divided into four groups, each containing eight
      rats. Torsion was created by rotating the right testis 720 degrees in a clockwise
      direction. Group 1 underwent sham operation to determine basal values for
      biochemical and histopathological evaluation. Sham operation was performed in
      group 2, and sodium selenate (0.2 mg/kg) was given intraperitoneally. Group 3
      served as a T/D group, receiving 4-h torsion and 4-h detorsion. Similarly, in
      group 4 sodium selenate (0.2 mg/kg) was injected intraperitoneally 20 min before
      detorsion. Bilateral orchiectomies were performed for measurement of tissue
      malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities and
      histopathologic examination. The results were compared statistically. The highest
      MDA and the lowest SOD values were determined in both testes in group 3. There
      were statistically significant differences in MDA levels and SOD activities in
      group 3 compared with group 4. Specimens from group 3 had a significantly greater
      histologic injury than other groups. These results suggest that ischemia
      reperfusion injury occurred in both testes after unilateral testicular T/D and
      that selenium administration before detorsion prevents reperfusion injury in
      testicular torsion.

PMID- 15742188
TI  - Cytogenetic analysis of 52 Indian patients with de novo myelodysplastic syndromes
      a comparative analysis of results with reports from Asia.
AB  - Most published data on myelodysplastic syndromes (MDS) are derived from Western
      countries, which report MDS as a disease of the elderly. However, it was observed
      that Asian MDS patients were younger than subjects in Western reports. With this
      in mind, the study was conducted prospectively on 52 Indian patients to define
      chromosomal abnormalities and to understand ethno-geographical differences, if
      any, underlying the pathogenesis of MDS among this Asian population. Cytogenetic
      analysis was performed using GTG banding and karyotyped according to the
      International System for Human Cytogenetic Nomenclature (ISCN). The incidence of
      MDS was predominant in the age group of 41-60 years (44.23%), with a median age
      at diagnosis of 55 years. The disease was more frequent in males (33 patients,
      63.46%) than females (19 patients, 36.53%). Of 48 patients successfully
      karyotyped, 17 had normal karyotype (35.4%) and 31 patients (64.5%) had a
      chromosomal abnormality. The most frequent chromosome abnormalities were del 5q/
      5 in 13 patients (42%), -7/7q- in 10 patients (32.2%), +8 and del 20q- in 6 cases
      each (19.3%) and i(17)(q10) in 1 patient (3.2%). In addition to these non-random
      chromosomal abnormalities, some rare abnormalities were also encountered. A
      higher rate of transformation to acute myeloid leukaemia (AML) was observed in
      the Chinese population compared to other Asian countries. The incidence of
      chromosomal abnormalities varied considerably across the different Asian
      populations. The overall frequency of chromosomal abnormalities in our study was
      comparable to most Western reports. Further prospective studies are warranted to
      elucidate precisely the ethnic differences in the pathogenesis of MDS in the
      Indian population.

PMID- 15742189
TI  - Evaluation of the Turkish version of the Dougados functional index in ankylosing
      spondylitis.
AB  - To investigate the reliability and validity of the Turkish version of the
      Dougados functional index (DFI) in patients with ankylosing spondylitis (AS). The
      Turkish version of DFI was obtained after a translation and back-translation
      process. Seventy consecutive patients with AS were enrolled. Patients were
      requested to complete the questionnaire on the day of admission (first visit), a
      second time within 24 h after admission (second visit), and on a third occasion.
      Reliability, validity and reproducibility of the Turkish version of the index
      were assessed. All the items showed significant correlations with the total index
      score with r-values ranging from 0.516 to 0.817. Cronbach alpha score was
      calculated as 0.908. Significant correlations were found between the total DFI
      score and Schober test (r=-0.293, P<0.05), occiput-wall distance (r=0.384;
      P<0.01) finger-to-floor distance (r=0.450, P<0.001), chest expansion (r=-0.331,
      P<0.01) and Dougados articular index (r=0.352, P<0.05). Good correlations were
      found between individual DFI items and the total score (r=between 0.533 and
      0.882, p< 0.001) for the first and second visits, showing good reproducibility of
      the index. CONCLUSION: the Turkish version of DFI has good reliability, validity
      and reproducibility, confirming its utility for trials in Turkish AS patients.

PMID- 15742190
TI  - Ten-year results of uncemented hip stems for failed intertrochanteric osteotomy.
AB  - INTRODUCTION: Inferior survival of cemented total hip arthroplasty has been
      reported after previous femoral osteotomy. The purpose of this study was to
      evaluate the long-term survival of uncemented stems after femoral osteotomy.
      MATERIALS AND METHODS: Forty-eight hips in 45 patients had undergone conversion
      THA for a failed intertrochanteric osteotomy of the hip after a mean of 12 years
      (2-33 years). Mean time of follow-up was 11 years (5-15 years). RESULTS: At
      follow-up, two patients (three hips) had died, and one patient (one hip) was not
      located. Three patients (three hips) underwent femoral revision-one for infection
      and two for aseptic loosening of the stem. Survival of the stem was 94% at 10
      years, and survival with femoral revision for aseptic loosening as an end point
      was 96%. The median Harris Hip Score at follow-up was 80 points. Radiolucent
      lines in Gruen zones 1 and 7 were present in 14 and 18% of hips, respectively.
      Radiolucencies in other zones were not detected. There was no radiographic
      evidence of femoral osteolysis, stress-shielding or loosening. CONCLUSION: The
      results with this type of uncemented tapered titanium femoral component after
      proximal femoral osteotomy are encouraging and compare to those achieved in
      patients with regular femoral anatomy.

PMID- 15742191
TI  - Operative treatment of acetabular fracture during pregnancy: a case report.
AB  - We present a case of operative treatment of an acetabular fracture in a pregnant
      patient in her third trimester. The natural fear of causing harm to the pregnancy
      or fetus is understandable in such situations, but should not lead to withholding
      appropriate care. Successful treatment of these rare cases is possible with
      careful pre-, peri-, and postoperative evaluation of the mother and fetus by a
      multidisciplinary team.

PMID- 15742193
TI  - Observer assessment of femoral neck radiographs after reduction and dynamic hip
      screw fixation.
AB  - INTRODUCTION: It is not known how the described methods of reduction and dynamic
      hip screw (DHS) fixation of displaced intracapsular femoral neck fractures
      translate into proper assessment of the postoperative radiographs. At teaching or
      evaluation sessions in daily practice, frequent discussion arises about
      postoperative technical assessment. The assessment of correct reduction and DHS
      fixation using the described methods in the literature may be subject to
      differences between observers. The aim of this study was to assess the extent of
      inter- and intraobserver agreement on technique, based on the methods in the
      literature, in a simulated daily practice setting. MATERIALS AND METHODS: The
      postoperative anteroposterior (AP) and lateral radiographs of 35 randomly
      selected patients aged 60-90 years were rated twice, 2 months apart, by six
      surgical observers from three institutions with similar views on reduction and
      DHS fixation for this fracture type. The radiographs were of sufficient quality
      for proper assessment. Criteria for reduction and fixation could be rated as
      either adequate or inadequate. An adequate rating was assigned if in the
      observer's opinion, regardless of likely outcome, technical perfection according
      to the described methods had been achieved. The kappa statistic was calculated as
      a measure of agreement. RESULTS: Fracture reduction on the AP view approached a
      good kappa value (0.54). Poor to moderate interobserver agreement was found for
      fracture reduction on the lateral view and aspects of DHS fixation (kappa 0.10
      0.36). Intraobserver agreement was good for five out of six observers for
      reduction and DHS fixation aspects (kappa 0.51-0.81). CONCLUSION: During routine
      practice six surgical observers can nearly agree on adequate fracture reduction
      on the AP view, but do not agree on adequate reduction on the lateral view and
      adequate DHS fixation on the postoperative radiographs of displaced intracapsular
      femoral neck fractures.

PMID- 15742194
TI  - Comparing biomechanical investigations about different wiring techniques of
      finger joint arthrodesis.
AB  - INTRODUCTION: Multiple operative techniques are currently used for finger
      arthrodesis in clinical practice. The present study was designed to compare the
      biomechanical characteristics of typical arthrodesis techniques used in daily
      practice. MATERIAL AND METHODS: Osteosynthesis techniques comprising wire
      cerclage, thread cerclage (PDS) or intraosseous wire suture were compared in a
      biomechanical experiment for resistance against bending loads. The mentioned
      techniques were applied to artificial specimens with resected articular surfaces
      or by using the cup-and-cone procedure. In this process, the specimens were
      tested using various Kirschner-wire insertion angles as well as different
      arthrodesis angles (20 degrees vs 40 degrees) in a 4-point bending test with each
      group consisting of 6 specimens of acrylic glass. The forces prevalent in the
      joint space were determined by prescale pressure measurement foils. RESULTS: Wire
      tension banding resisted significantly higher bending moments than arthrodeses
      with thread tension bands (p < 0.05). All set-ups with tension banding techniques
      tolerated significantly higher loads than the intraosseous wire sutures without
      additional K-wires (p < 0.05), which showed unfavorable dislocation of contact
      areas resulting in instability even under relatively minor bending loads. Using
      the cup-and-cone technique, a geometrically larger contact area could be achieved
      between two unloaded fragments, but this technique showed no advantages in the
      opposing bending moments compared with the conventional resection method. In both
      techniques, a dislocation of contact surfaces towards the palmar direction could
      be observed with increasing bending moment. While the use of thread tension band
      fixation reduces the risk of plastic deformation of both osteosynthetic material
      and bone stock, the problem of resorption rate has to be taken into account when
      choosing the material for the thread. CONCLUSIONS: Considering pressure
      distribution and stability with and without bending loads, it is not the most
      rigid osteosynthesis technique which should be viewed as the ideal treatment. In
      contrast, it is more important to consider the various and most likely conditions
      to be expected in daily life after arthrodesis and therefore to chose the type of
      technique distributing pressure as regularly as possible.

PMID- 15742195
TI  - Adaptive mechanisms during food restriction in Acomys russatus: the use of torpor
      for desert survival.
AB  - The golden spiny mouse (Acomys russatus) is an omnivorous desert rodent that does
      not store food, but can store large amounts of body fat. Thus, it provides a good
      animal model to study physiological and behavioural adaptations to changes in
      food availability. The aim of this study was to investigate the time course of
      metabolic and behavioural responses to prolonged food restriction. Spiny mice
      were kept at an ambient temperature of 27 degrees C and for 3 weeks their food
      was reduced individually to 30% of their previous ad libitum food intake. When
      fed ad libitum, their average metabolic rate was 82.77+/-3.72 ml O(2) h(-1)
      during the photophase and 111.19+/-4.30 ml O(2) h(-1) during the scotophase.
      During food restriction they displayed episodes of daily torpor when the minimal
      metabolic rate gradually decreased to 16.07+/-1.07 ml O(2) h(-1), i.e. a
      metabolic rate depression of approximately 83%. During the hypometabolic bouts
      the minimum average body temperature T(b), decreased gradually from 32.6+/-0.1
      degrees C to 29.0+/-0.4 degrees C, with increasing duration of consecutive bouts.
      In parallel, the animals increased their activity during the remaining daytime.
      Torpor as well as hyperactivity was suppressed immediately by refeeding. Thus
      golden spiny mice used two simultaneous strategies to adapt to shortened food
      supply, namely energysaving torpor during their resting period and an increase in
      locomotor activity pattern during their activity period.

PMID- 15742196
TI  - Senescence-associated alterations of cytoskeleton: extraordinary production of
      vimentin that anchors cytoplasmic p53 in senescent human fibroblasts.
AB  - The cytoskeleton of senescent cells was systematically studied using senescent
      and young fibroblasts. In the cell senescence, skin fibroblasts extraordinarily
      produced vimentin in contrast to actin and tubulin, which were down-regulated.
      Among the focal adhesion proteins, paxillin and c-Src decreased also. Senescent
      cells developed a long and dense vimentin network, long and thin actin fibers,
      and numerous small focal contact sites, which contrasted with young cells with
      short and thick actin stress fibers and prominently large focal adhesions.
      Noticeably, senescent fibroblasts markedly produced p53 molecules and anchored
      them to vimentin-cytoskeleton in the cytoplasm. The vimentin-anchored p53 was
      detected with antibody PAb240 that specifically recognizes a conformation variant
      of p53. A GFP-tagged wild type p53 cDNA was expressed by transfection and shown
      also to be retained in the cytoplasm in senescent cells, suggesting that p53 is
      structurally modified to be recognized by PAb240 and anchored to vimentin
      filaments. We discuss the correlation of the marked alteration of cytoskeleton
      and senescent cells' diminished proliferation and migration, as well as the
      significance of cytoskeletal anchorage of tumor suppressor p53.

PMID- 15742197
TI  - Orexin inputs to caudal raphe neurons involved in thermal, cardiovascular, and
      gastrointestinal regulation.
AB  - Orexin-expressing neurons in the lateral hypothalamus with their wide projections
      throughout the brain are important for the regulation of sleep and wakefulness,
      ingestive behavior, and the coordination of these behaviors in the environmental
      context. To further identify downstream effector targets of the orexin system, we
      examined in detail orexin-A innervation of the caudal raphe nuclei in the
      medulla, known to harbor sympathetic preganglionic motor neurons involved in
      thermal, cardiovascular, and gastrointestinal regulation. All three components of
      the caudal raphe nuclei, raphe pallidus, raphe obscurus, and parapyramidal
      nucleus, are innervated by orexin-A-immunoreactive fibers. Using confocal
      microscopy, we demonstrate close anatomical appositions between varicose orexin-A
      immunoreactive axon profiles and sympathetic premotor neurons identified with
      either a transneuronal retrograde pseudorabies virus tracer injected into the
      interscapular brown fat pads, or with in situ hybridization of pro-TRH mRNA.
      Furthermore, orexin-A injected into the fourth ventricle induced c-Fos expression
      in the raphe pallidus and parapyramidal nucleus. These findings suggest that
      orexin neurons in the hypothalamus can modulate brown fat thermogenesis,
      cardiovascular, and gastrointestinal functions by acting directly on neurons in
      the caudal raphe nuclei, and support the idea that orexin's simultaneous
      stimulation of food intake and sympathetic activity might have evolved as a
      mechanism to stay alert while foraging.

PMID- 15742198
TI  - The moving parts of the nucleolus.
AB  - The cell nucleolus is the subnuclear body in which ribosomal subunits are
      assembled, and it is also the location of several processes not related to
      ribosome biogenesis. Recent studies have revealed that nucleolar components move
      about in a variety of ways. One class of movement is associated with ribosome
      assembly, which is a vectorial process originating at the sites of transcription
      in the border region between the fibrillar center and the dense fibrillar
      component. The nascent preribosomal particles move outwardly to become the
      granular components where further maturation takes place. These particles
      continue their travel through the nucleoplasm for eventual export to the
      cytoplasm to become functional ribosomes. In a second kind of motion, many
      nucleolar components rapidly exchange with the nucleoplasm. Thirdly, nucleolar
      components engage in very complex movements when the nucleolus disassembles at
      the beginning of mitosis and then reassembles at the end of mitosis. Finally,
      many other cellular and viral macromolecules, which are not related to ribosome
      assembly, also pass through or are retained by the nucleolus. These are involved
      in nontraditional roles of the nucleolus, including regulation of tumor
      suppressor and oncogene activities, signal recognition particle assembly,
      modification of small RNAs, control of aging, and modulating telomerase function.

PMID- 15742200
TI  - Apoptosis of Merkel cells in neurotrophin-3 null mice.
AB  - Postnatal mice lacking neurotrophin-3 (NT3) are deficient in Merkel cells of
      touch domes and whisker follicles. We examined the mechanism of Merkel cell loss
      by immunocytochemistry and electron microscopy. Merkel cell of whisker follicles
      of NT3 null newborns exhibited decreased immunoreactivity for cytokeratin 8 and
      contained apoptotic bodies that were positive for cleaved caspase-3, a marker of
      active apoptosis. By electron microscopy, the Merkel cells displayed aggregation
      of chromatin along the nuclear membrane, with the marginated chromatin forming
      caps at the periphery of the nucleus. Ribosomes aggregated in the cytoplasm,
      while dense core granules characteristic of Merkel cells were still discernible.
      Finally, the Merkel cells and their nuclei fragmented into apoptotic bodies. None
      of the apoptotic Merkel cells were contacted by nerve fibers, and their
      desmosomal contacts with surrounding keratinocytes disappeared. After postnatal
      day 6 apoptotic Merkel cells were no longer observed, and the number of surviving
      Merkel cells was severely reduced. They were flat and contained few osmiophilic
      granules. We conclude that perinatal apoptosis is responsible for the loss of
      Merkel cells lacking innervation in NT3 null mice.

PMID- 15742199
TI  - Compensation for and adaptation to changes in the environment.
AB  - Human motor behavior is remarkably accurate, even though many everyday skills
      require flexible adjustments between motor activity and its consequences in
      extracorporeal space. The present study addressed two questions: first, how do
      people compensate for unpredictable changes in the environment, and second, how
      do they adapt to such changes? In Experiment 1, participants repeatedly and
      continuously drew up and down strokes on a writing pad. After drawing under a
      base mapping, either (a) a change of target position, or (b) a change of gain, or
      (c) both occurred. Compensation for gain changes occurred later than compensation
      for changes in target position. In addition, there were aftereffects of the
      previous movement in accuracy and movement time. Adaptation to changes occurred
      in reference to extracorporeal space, with motor constraints as a limiting
      factor. In Experiment 2 we obtained similar effects when participants had more
      time to adapt. The view that movements are planned in reference to their goals in
      extracorporeal space is supported.

PMID- 15742201
TI  - Structural development of PGP9.5-immunopositive myenteric plexus in embryonic
      rats.
AB  - To investigate relationships between changes in the 3-dimensional structure of
      the myenteric plexus and the time at which functional movement of intestine
      begins in mammalian embryos, whole mounts of embryonic rat intestine were
      examined under confocal laser scanning microscopy on spacer-equipped glass slides
      after immunostaining with antiprotein gene product 9.5 antibody. At embryonic day
      12.5, very few nerve cells were scattered throughout the small intestine, but no
      immunostained structures were apparent on the anal side of the large intestine.
      At embryonic day 13.5, immunostained fibers appeared on the oral side of the
      large intestine. Nerve cells and associated fiber bundles formed neuronal
      networks with large meshes in both intestines. Marked increases in number of
      nerve fibers and decreases in mesh size were seen in the small intestine between
      embryonic days 13.5 and 15.5. Similar changes were found in the large intestine
      between embryonic days 13.5 and 16.5. After embryonic day 16.5, nerve cells were
      arranged parallel to circular muscle fibers, and networks formed by cell fibers
      elongated until the neonatal period in both intestines. Meconium passed through
      the large intestine from embryonic day 17.5. Thin fiber bundles extended from the
      ganglion to the inner side of the myenteric layer, parallel (and occasionally
      extending) to the circular muscle fibers. Formation of nerve fiber networks and
      arrangement of nerve cells parallel to circular muscle fibers probably relate to
      movement coordination for inner circular muscle fibers in the intestinal wall,
      and development of this neural network may be important for acquiring intestinal
      movements before birth.

PMID- 15742202
TI  - DArT for high-throughput genotyping of Cassava (Manihot esculenta) and its wild
      relatives.
AB  - Understanding the distribution of genetic diversity within and among individuals,
      populations, species and gene pools is crucial for the efficient management of
      germplasm collections. Molecular markers are playing an increasing role in
      germplasm characterization, yet their broad application is limited by the
      availability of markers, the costs and the low throughput of existing
      technologies. This is particularly true for crops of resource-poor farmers such
      as cassava, Manihot esculenta. Here we report on the development of Diversity
      Arrays Technology (DArT) for cassava. DArT uses microarrays to detect DNA
      polymorphism at several hundred genomic loci in a single assay without relying on
      DNA sequence information. We tested three complexity reduction methods and
      selected the two that generated genomic representations with the largest
      frequency of polymorphic clones (PstI/TaqI: 14.6%, PstI/BstNI: 17.2%) to produce
      large genotyping arrays. Nearly 1,000 candidate polymorphic clones were detected
      on the two arrays. The performance of the PstI/TaqI array was validated by typing
      a group of 38 accessions, 24 of them in duplicate. The average call rate was
      98.1%, and the scoring reproducibility was 99.8%. DArT markers displayed fairly
      high polymorphism information content (PIC) values and revealed genetic
      relationships among the samples consistent with the information available on
      these samples. Our study suggests that DArT offers advantages over current
      technologies in terms of cost and speed of marker discovery and analysis. It can
      therefore be used to genotype large germplasm collections.

PMID- 15742203
TI  - Chromosomal rearrangements differentiating the ryegrass genome from the
      Triticeae, oat, and rice genomes using common heterologous RFLP probes.
AB  - An restriction fragment length polymorphism (RFLP)-based genetic map of ryegrass
      (Lolium) was constructed for comparative mapping with other Poaceae species using
      heterologous anchor probes. The genetic map contained 120 RFLP markers from cDNA
      clones of barley (Hordeum vulgare L.), oat (Avena sativa L.), and rice (Oryza
      sativa L.), covering 664 cM on seven linkage groups (LGs). The genome comparisons
      of ryegrass relative to the Triticeae, oat, and rice extended the syntenic
      relationships among the species. Seven ryegrass linkage groups were represented
      by 10 syntenic segments of Triticeae chromosomes, 12 syntenic segments of oat
      chromosomes, or 16 syntenic segments of rice chromosomes, suggesting that the
      ryegrass genome has a high degree of genome conservation relative to the
      Triticeae, oat, and rice. Furthermore, we found ten large-scale chromosomal
      rearrangements that characterize the ryegrass genome. In detail, a chromosomal
      rearrangement was observed on ryegrass LG4 relative to the Triticeae, four
      rearrangements on ryegrass LGs2, 4, 5, and 6 relative to oat, and five
      rearrangements on ryegrass LGs1, 2, 4, 5, and 7 relative to rice. Of these, seven
      chromosomal rearrangements are reported for the first time in this study. The
      extended comparative relationships reported in this study facilitate the transfer
      of genetic knowledge from well-studied major cereal crops to ryegrass.

PMID- 15742204
TI  - Predictive value of gadolinium enhancement in differentiating ALT/WD liposarcomas
      from benign fatty tumors.
AB  - OBJECTIVE: To determine the predictive value of gadolinium enhancement on MRI in
      differentiating atypical lipomatous tumor (ALT)/well-differentiated (WD)
      liposarcoma from benign fatty tumors. DESIGN: All histologically proven fatty
      tumors with preoperative gadolinium-enhanced MRI were reviewed. Only those tumors
      with predominantly fatty signal were included. Sensitivity, specificity, and
      positive and negative predictive values for both gadolinium enhancement and
      biopsy as predictors for the final diagnosis of ALT/WD liposarcoma were
      calculated. PATIENTS: From 129 patients evaluated for fatty tumors between 1994
      and 2002, the patient population was narrowed to 32 excised fatty tumors with
      preoperative gadolinium-enhanced MRI. RESULTS: As a predictor of ALT/WD
      liposarcoma, the presence of gadolinium enhancement showed 100% sensitivity, 71%
      specificity, 53% positive predictive value and 100% negative predictive value.
      Needle or incisional biopsy yielded 57% sensitivity, 100% specificity, 100%
      positive predictive value and 63% negative predictive value for a diagnosis of
      ALT/WD liposarcoma. CONCLUSIONS: Gadolinium enhancement of a homogeneous fatty
      soft tissue tumor is a sensitive screening tool to determine possible diagnosis
      of ALT/WD liposarcoma. Biopsy, on the other hand, is specific but insensitive.

PMID- 15742205
TI  - [Prevalence of urinary incontinence in the German population].
AB  - The purpose of this study was to determine the frequency of incontinence in men
      and women in different age groups. In a representative survey, 883 men and 1,182
      women with a mean age of 50 years (18-92 years) were studied based on
      standardized questionnaires on physical and psychological complaints, and quality
      of life. Participants suffering from involuntary loss of urine were considered
      "incontinent". The frequency of incontinence strongly increased with age, from
      6.9% among the 18-40 year old population to 9.5% among the 41-60 year olds and
      23% over the age of 60 years. Women complained more frequently of incontinence
      (15%) than men (9.5%; total of 12.6% in the population). The majority of the
      participants with incontinence also suffered from urinary urge, multiple
      disorders of digestion, pelvic pain and sexual dysfunction. There was also a
      strong increase in exhaustion, gastric pain, joint pain and cardiac complaints.
      The younger participants were more strongly affected by incontinence. When
      patients complain of incontinence, strong impairments in physical and
      psychological well-being, and quality of life are to be expected.

PMID- 15742206
TI  - [Sperm stains in legal medicine. An historical review of forensic authentication
      methods].
AB  - Furnishing proof of human seminal stains is part of daily forensic work in
      investigations of sexual crimes. In the last two centuries different methods have
      been described for confirming putative sperm traces. These methods ranged from
      identification of the smell and appearance of the stain, to simple chemical
      reactions such as precipitation of crystals and enzymatic proof of acid
      phosphatase, which are now enhanced by analytic methods of modern molecular
      biology. This discourse gives a review of the development of different forensic
      methods for detection of sperm traces, illustrated with historical case studies.

PMID- 15742207
TI  - [Diagnosis of septic loosening of hip prosthesis with LeukoScan. SPECT scan with
      99mTc-labeled monoclonal antibodies].
AB  - Diagnosis of septic loosening of hip endoprosthesis with antigranulocyte
      scintigraphy (AGS) was analysed. Twenty-one hip prostheses were studied using
      laboratory tests and, in cases of elevated values, three-phase bone scan (BS) and
      AGS. Elective SPECT/CT scans were performed. Histologic and microbiologic exams
      verified the diagnosis. The AGS analysis revealed sensitivity, specificity and
      accuracy of value 1, while positive and negative predictive values were also 1.
      BS showed sensitivity of 1 and specificity of 0.33. In three cases, SPECT/CT
      scans corroborated the AGS interpretation. This diagnostic algorithm proved
      effective in the detection of septic loosening of hip prostheses. AGS can be
      avoided without risk of infection being overlooked.

PMID- 15742208
TI  - Primary lumbosacral Wilms tumor associated with diastematomyelia and occult
      spinal dysraphism. A report of a rare case and a short review of literature.
AB  - BACKGROUND: The occurrence of an extrarenal Wilms tumor in the lumbosacral region
      is an extremely uncommon condition. CASE REPORT: We report a case of Wilms tumor
      in the lumbosacral region that was associated with diastematomyelia and occult
      spina bifida. An 18-month-old girl presented with a swelling over the lower back
      with a tuft of hair on it, which she had had since birth. Imaging of the spine
      revealed spina bifida, bony diastematomyelia, and tethered cord. Excision of the
      bony spur and detethering of the cord was done. After a year, she had recurrence
      of swelling at the same site, weakness of both lower limbs, and incontinence of
      bladder and bowel. Excision of the mass and bony spur and detethering of the
      spinal cord were done. Histopathological examination showed features of a Wilms
      tumor.

PMID- 15742209
TI  - Extradural hematoma causing venous sinus obstruction and pseudotumor cerebri
      syndrome.
AB  - CASE REPORT: The case of a small right occipital extradural hematoma in a 10-year
      old girl is presented. The patient had bifrontal occipital headache out of
      proportion to the size of the hematoma, as well as diplopia. MR venography
      revealed compression and occlusion of the dominant right transverse sinus
      resulting in a pseudotumor cerebri syndrome. DISCUSSION: The relationship between
      venous sinus obstruction and the pseudotumor syndrome is discussed. Clinicians
      should be aware of the possible effects of an extra-axial collection on the
      cerebral venous sinuses.

PMID- 15742210
TI  - Tear flow dynamics in the human nasolacrimal ducts--a pilot study using dynamic
      magnetic resonance imaging.
AB  - BACKGROUND: Jones's theory of tear drainage suggests that the lacrimal sac fills
      when the eyelids are closed and empties into the nasolacrimal duct when the
      eyelids are open. This is aided by the contraction of the orbicularis muscle
      during each blink. This study was undertaken to ascertain the possibility of
      seeing the dynamic movement of tears in the nasolacrimal system during blinks
      using magnetic resonance dacryocystography (MR-DCG). METHODS: The sac was
      initially localized with a three-plane gradient echo sequence using a 1.5-T MRI
      platform. Fast, dynamic MR-DCG was carried out after we had instilled topically
      balanced salt solution (BSS) in five subjects and 0.5% gadolinium in seven
      subjects. The volunteers were asked to close and open their eyes during the fast
      imaging. The images were digitized to enable us to see the actual movement of
      fluid in the system. RESULTS: The tear movement was clearly seen as a bolus in
      the volunteers where BSS was used. The fluid passed into the nasolacrimal duct
      after several blinks when patent. The sac was never seen to empty completely.
      Though differential filling was seen between the upper and lower part of the sac,
      it was difficult to see the actual fluid movement in the volunteers when topical
      gadolinium was used. CONCLUSION: The findings of the study are supportive of the
      notion of fluid travel in the form of a bolus through the sac. Once a threshold
      volume is reached in the lower end of the sac, the fluid is seen to pass through
      the nasolacrimal duct. This happens after several blinks.

PMID- 15742211
TI  - Multifocal electroretinograms combined with periodic flashes: direct responses
      and induced components.
AB  - PURPOSE: To investigate the retinal responses generated by flash interactions in
      a recently introduced "global (full-screen) flash" stimulus paradigm to record
      the multifocal electroretinogram (mfERG). METHODS: Five normal individuals were
      studied with stimulation combining multifocal (pseudorandom) flashes with
      interleaved global (periodic, full-screen) flashes. The intensities of the two
      flashes were independently varied. Two distinct first-order response components
      were obtained: the mean response to the focal flashes (referred to as the direct
      response, DR) and the effect of the focal flash on the responses evoked by the
      global flash (the induced component, IC). RESULTS: Increasing the global flash
      luminance reduced DR amplitude and shortened DR implicit time. IC amplitude
      peaked with a moderate global flash (1.33-2.67 cd.s/m2). With a global flash of
      the right intensity, a weak focal flash could evoke a considerable IC even when
      the DR was barely detectable. Moderate global flashes maximized the IC, and its
      intersubject variability was reduced at lower focal flash luminances. IC
      topography had a large naso-temporal asymmetry. CONCLUSIONS: While the DR is the
      average response generated by the local flashes regardless of the context of
      preceding and following flashes, the IC represents the difference in the global
      flash response in the presence and absence of the preceding focal flash. As the
      focal flashes were always preceded by the periodically occurring global flashes,
      the DR reflects the resulting adapted or desensitized state of the retinal patch.
      The pure, nonlinear IC is thought to reflect predominantly inner retinal
      function.

PMID- 15742212
TI  - Carbonic anhydrase inhibition increases retinal oxygen tension and dilates
      retinal vessels.
AB  - BACKGROUND: Carbonic anhydrase inhibitors (CAIs) increase blood flow in the brain
      and probably also in the optic nerve and retina. Additionally they elevate the
      oxygen tension in the optic nerve in the pig. We propose that they also raise the
      oxygen tension in the retina. We studied the oxygen tension in the pig retina and
      optic nerve before and after dorzolamide injection. Also the retinal vessel
      diameters during carbonic anhydrase inhibition were studied. METHODS: A
      polarographic oxygen electrode was placed transvitreally immediately over the
      retina or the optic disc in anaesthetised pigs. The oxygen tension was recorded
      continually and 500 mg dorzolamide was injected intravenously. Retinal vessel
      diameters were analysed from monochromatic fundus photographs taken before and
      after injection of dorzolamide. RESULTS: Baseline retinal oxygen tension (RPO2)
      was 3.34+/-0.50 kPa (mean +/- SD, n=6) and baseline optic nerve oxygen tension
      (ONPO2) was 3.63+/-1.00 kPa. RPO2 was increased by 0.36+/-0.11 kPa (n=6, P=0.025)
      and ONPO2 by 0.73+/-0.34 kPa (n=6, P=0.003) 30 min after dorzolamide
      administration. The retinal arterioles was significantly dilated by 13+/-7% (n=5,
      P=0.016) and the retinal venules by 12+/-8% (n=5, P=0.030) 30 min after injection
      of dorzolamide. CONCLUSION: Retinal and optic nerve oxygen tension increased with
      systemic administration of dorzolamide. The retinal vessels dilated, probably
      causing increased blood flow inducing the observed increase in RPO2. The
      increased oxygenation of retina by CAI may offer therapeutic possibilities in
      ischaemic diseases of the retina and optic nerve.

PMID- 15742213
TI  - Bilateral optic neuropathy and unilateral tonic pupil associated with acute human
      herpesvirus 6 infection: a case report.
AB  - BACKGROUND: Human herpesvirus 6 (HHV-6), a widespread virus and causative agent
      of exanthema subitum in children, has been associated with a number of neurologic
      disorders including cranial nerve palsies, seizures, encephalitis, meningitis,
      and multiple sclerosis. PATIENT: A 31-year-old man presented with bilateral optic
      neuropathy, disc edema, and unilateral tonic pupil, which were found to be
      associated with acute HHV-6 infection. The patient had been suffering from
      juvenile diabetes for 5 years. One week after onset of intravenous antiviral
      therapy with foscarnet, disc edema subsided, and tonic pupil reaction was no
      longer detectable. CONCLUSIONS: HHV-6 infection may play a role as a causative
      agent in patients with optic neuropathy and tonic pupil.

PMID- 15742215
TI  - NR2A and NR2B receptor gene variations modify age at onset in Huntington disease.
AB  - N -Methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity has been proposed
      to play a role in the pathogenesis of Huntington disease (HD), an autosomal
      dominantly inherited disorder associated with defined expansions in a stretch of
      perfect CAG repeats in the 5' part of the IT15 gene. The number of CAG repeat
      units is highly predictive for the age at onset (AO) in HD. However, AO is only
      modestly correlated with repeat length when the HD expansion range is in the high
      30s or low 40s. Therefore, we investigated whether the genes for the different
      subunits composing the multimeric complexes of NMDA receptors (GRIN glutamate
      receptor, ionotropic, N-methyl-d-aspartate) represent candidates for modulating
      the AO of HD. In the studied cohort of 167 HD patients, the repeat range from 41
      to 45 CAG units accounted for 30.8% of the variance in AO; 12.3% additional
      variance could be attributed to GRIN2B genotype variation and 4.5% to GRIN2A
      genotype variation. We conclude that these two genes, coding for NR2B and NR2A
      subtypes mainly expressed in the striatum, may influence the variability in AO of
      HD. Neuroprotective strategies for HD patients and persons at risk should be
      reconsidered in the light of these findings.

PMID- 15742217
TI  - Expanded FMR1 alleles are rare in idiopathic Parkinson's disease.

PMID- 15742218
TI  - Geographic variation in the life history of the sagebrush lizard: the role of
      thermal constraints on activity.
AB  - Thermal constraints on the time available for activity have been proposed as a
      proximate mechanism to explain variation in suites of life history traits. The
      longer that an ectotherm can maintain activity, the more time it has to forage
      and the greater chance that it will encounter a predator and be eaten. Thus, the
      thermal environment may produce a trade off between growth and survival when
      variation in the environment favors increased activity. I used mark-recapture
      data from a demographic study of three natural populations of the sagebrush
      lizard (Sceloporus graciosus) and estimates of thermal opportunity for each
      population to evaluate whether variation in the thermal environment can explain
      patterns of growth and survival that occur over an elevational gradient. Lizards
      from the highest elevation population exhibited higher individual growth rates
      than those of lizards from lower elevation, while mortality rates increased with
      elevation for these populations. The covariation of fast growth and high
      mortality with increased thermal opportunity is the opposite trend expected if
      the thermal environment alone is to explain patterns of life history in these
      lizards. Additional factors including thermal heterogeneity in the distribution
      of microhabitats of lizards, adaptation to local environmental conditions, and a
      potential trade-off between resource acquisition and predation risk need to be
      addressed to obtain a satisfactory explanation of the causative mechanisms
      producing life history variation.

PMID- 15742216
TI  - Functional polymorphisms in the human beta4 subunit of nicotinic acetylcholine
      receptors.
AB  - Human nicotinic acetylcholine receptor (nAChR) polymorphisms occur in different
      ethnic populations and may result in differences in nAChR ion channel properties.
      We have identified four nAChR beta 4 subunit (beta4) nucleotide variants: 392C-
      >T, 526C-->T, 538A-->G, and 1519A-->G. Their corresponding amino acid
      substitutions are: Thr to Ile at codon 91 (T91I), Arg to Trp at codon 136
      (R136W), Ser to Gly at codon 140 (S140G), and Met to Val at codon 467 (M467V),
      respectively. The nAChR ion channel properties of these variants were studied and
      compared with the more-common (wild-type) allele as wild-types. The nAChRs
      (alpha4beta4 channels) were expressed heterologously in Xenopus oocytes and
      studied using the two-electrode voltage clamp technique to reveal functional
      differences between the wild-type and the variants. The receptors containing the
      R136W and M467V mutations (or variants) had a higher sensitivity to acetylcholine
      and lower EC50 than the wild-type. The T91I mutation had lower sensitivity to
      acetylcholine and the EC50 was larger than in wild-type nAChRs. The S140G
      mutation had a dose-response relationship that was similar to the wild-type. The
      T91I, R136W, and M467V mutations (or variants) also showed a slightly greater
      degree of steady-state desensitization than the wild-type in response to a 30-min
      exposure to one tenth of their EC50. The present results demonstrate that human
      beta4 nAChR DNA polymorphisms result in functional changes, and suggest that
      certain individuals with those variants may be more or less sensitive to
      cholinergic drugs or to dysfunctions associated with nicotinic cholinergic
      systems.

PMID- 15742219
TI  - Herbivore attack in Casearia nitida influenced by plant ontogenetic variation in
      foliage quality and plant architecture.
AB  - Traits influencing plant quality as food and/or shelter for herbivores may change
      during plant ontogeny, and as a consequence, influence the amount of herbivory
      that plants receive as they develop. In this study, differences in herbivore
      density and herbivory were evaluated for two ontogenetic stages of the tropical
      tree Casearia nitida. To assess plant ontogenetic differences in foliage quality
      as food for herbivores, nutritional and defensive traits were evaluated in
      saplings and reproductive trees. Predatory arthropods were quantified and the
      foraging preferences of a parasitoid wasp of the genus Zacremnops were assessed.
      In addition, survival rates of lepidopteran herbivores (Geometridae) were
      evaluated experimentally. Herbivore density was three times higher and herbivory
      was 66% greater in saplings than in reproductive trees. Accordingly,
      concentrations of total foliar phenolics were higher in reproductive trees than
      in saplings, whereas leaf toughness, water and nitrogen concentration did not
      vary between ontogenetic stages. Survival rates of lepidopteran larvae exposed to
      natural enemies were equivalent in reproductive trees and saplings. Given the
      greater herbivore density on saplings, equal survival rates implied a greater
      foraging effort of predators on reproductive trees. Furthermore, observed
      foraging of parasitoid wasps was restricted to reproductive trees. I propose that
      herbivore density, and as a consequence, leaf damage were lower in reproductive
      trees than in saplings due to both traits influencing food quality, and
      architectural or unmeasured indirect defensive traits influencing foraging
      preference of natural enemies of herbivores.

PMID- 15742221
TI  - Social environment factors associated with suicide attempt among low-income
      African Americans: the protective role of family relationships and social
      support.
AB  - BACKGROUND: Suicide and suicide attempts are important public health concerns,
      and recent decades have witnessed a rising rate of suicide among African
      Americans. A history of prior attempts is a leading risk factor for completed
      suicide. Further research is needed into the social environment risk factors for
      suicide attempt among African Americans. This study focused on two important
      dimensions of the social environment, family relationships and social support, as
      well as an important person-level risk factor--depressive symptoms. METHOD: Data
      were obtained from a case-control study of 200 African American men and women
      aged 18-64 years, who sought services at a large, urban, public hospital. Odds
      ratios adjusted for significant sociodemographic differences between groups
      (aORs) were calculated for environment risk factors for suicide attempt among the
      cases and controls. The role of depressive symptoms was also studied. RESULTS:
      Lower levels of family adaptability and family cohesion increased the relative
      rate of suicide attempt in the sample. The aOR associated with the lowest
      quartile of family adaptability was 3.90, and the aORs associated with the first
      and second quartiles of family cohesion were 8.91 and 5.51, respectively. Lower
      levels of social embeddedness and social support increased the relative rate of
      suicide attempt in our sample. The aOR associated with the first and second
      quartiles of social embeddedness were 5.67 and 4.93, respectively, and the aOR
      associated with the lowest quartile of social support was 6.29. A mediating role
      of depression was discovered when depressive symptoms were entered into the
      logistic regression models. CONCLUSIONS: Our findings indicate that social
      environment factors including deficits in family functioning and social support
      are associated strongly with suicide attempts among low-income African American
      men and women seeking treatment in a large, urban hospital. Thus, better family
      functioning and social supports can be considered protective factors in this
      population. The presence of depressive symptoms, a well-known risk factor for
      suicide attempts and suicide, appears to mediate the association between social
      environment factors and suicide attempt.

PMID- 15742220
TI  - Mixed inoculations of a microsporidian parasite with horizontal and vertical
      infections.
AB  - Mixed infections, where more than one parasite genotype is present in a single
      host, have been suggested to be an important factor in host-parasite
      interactions. As the host represents a limited resource, co-infecting parasite
      genotypes are expected to be under resource competition. Competition will not
      only modify the survival of the co-infecting genotypes, but is also likely to
      affect total within-host parasite growth as well as host survival and
      reproduction. We measured parasite infectivity and spore production of seven
      isolates of Octosporea bayeri (Microsporidia) and their effect on the
      reproduction and longevity of its host Daphnia magna (Cladocera), after single-
      or double-isolate inoculations through vertical and horizontal transmission.
      Double-isolate inoculations increased parasite infectivity and total spore
      production in horizontal infections, but had no significant effect on host
      reproduction or longevity. The increase in spore production in double-isolate
      inoculations was not found when infections occurred vertically. Our results
      suggest that, depending on the way the infection was acquired, within-host
      reproduction can increase as a result of parasite genetic diversity, without
      necessarily affecting the host's fitness. Whether this challenges the current
      views of virulence evolution depends on the definitions used.

PMID- 15742223
TI  - Age-period-cohort analysis of suicide rates in Rio de Janeiro, Brazil, 1979-1998.
AB  - BACKGROUND: Recent studies in Brazil have demonstrated that suicide rates have
      been rising over the last years. The objective of this study was to investigate
      trends in suicide from 1979 to 1998 in Rio de Janeiro State, with emphasis on
      age, period, and cohort effects. METHOD: Age-specific suicide rates from 1979 to
      1998 were estimated for males and females based on mortality data obtained from
      the Brazilian Mortality Information System, and population counts from the 1980,
      1991 and 2000 censuses. Poisson regression and graphical methods were used to
      evaluate age, period and cohort effects. RESULTS: Suicide rates increased
      steadily with age, particularly among males. In both males and females, age
      adjusted suicide rates decreased until 1992. In 1993, rates started to rise.
      Cohort effects showed that younger generations had significantly lower rates of
      suicide than older ones. CONCLUSION: The recent rise in suicide rates might be a
      result of the increasing levels of firearm availability, drug use, and
      unemployment. Follow-up over longer periods and powerful epidemiological studies
      are needed to sustain the implication of socio-economic changes in the observed
      features.

PMID- 15742222
TI  - Social predictors of suicidal behaviour in adolescents in Trinidad and Tobago.
AB  - BACKGROUND: Previous research in Trinidad and Tobago has been limited in
      examining suicidal behaviours through psychological autopsy, secondary data and
      psychiatric populations. To date, there has been no community survey with an
      emphasis on causation and prevention. METHODS: A total of 1,845 respondents aged
      14-20 were selected in 24 schools across the country. Data were collected on
      socio-demographic variables and suicidal behaviour. RESULTS: Gender differences
      existed for both suicidal ideation and attempts (p<0.001). Respondents from
      reconstituted families had higher suicidal ideation compared to other family
      structures (p<0.001), while intact families had the lowest rate for suicide
      attempts (p<0.01). Attendance to a religious institution lowered only suicidal
      ideation (p<0.05), while prayer with the family lowered both suicidal ideation
      (p<0.01) and suicide attempts (p<0.001). Individuals with alcohol abuse in the
      family had higher suicidal ideation (p<0.001) and attempts (p<0.001).
      CONCLUSIONS: Significant social predictors of suicidal behaviour in Trinidad and
      Tobago are gender, attendance to a religious institution, prayer with the family,
      family structure and alcohol abuse in the family. It is essential to consider
      these predictors in planning public health policies.

PMID- 15742224
TI  - Gender differences in patients presenting with a single depressive episode
      according to ICD-10.
AB  - BACKGROUND: It is unsure whether men and women present with different subtypes of
      depression. The aim of the study was to compare the prevalence of subtypes of a
      single depressive episode according to ICD-10 for men and women in a nationwide
      sample of all patients treated in psychiatric in- or outpatient settings.
      METHODS: All patients who got a diagnosis of a single depressive episode in a
      period from 1994 to 2002 at the end of the first outpatient treatment ever or at
      the first discharge from psychiatric hospitalisation ever in Denmark were
      identified in a nationwide register. RESULTS: A total of 18,192 patients got a
      diagnosis of a single depressive episode at the first outpatient contact ever and
      8,396 patients got a diagnosis of a single depressive episode at the first
      psychiatric hospitalisation ever. Significantly more women were treated as
      outpatients than as inpatients (68% vs. 60.4%). In outpatient settings, women
      slightly more often presented with milder types of depression than with severe
      depression, but no gender difference was found in the severity of depressive
      episodes among hospitalised patients. No differences were found between genders
      in the prevalence of depression with vs. without melancholic or psychotic
      symptoms in either of the settings. Women were treated for longer periods in both
      settings. CONCLUSIONS: The distributions of the subtypes of a single depressive
      episode are remarkably similar for male and female patients with first contact to
      the psychiatric health care system.

PMID- 15742225
TI  - Depressive symptoms in mothers of pre-school children--effects of deprivation,
      social support, stress and neighbourhood social capital.
AB  - BACKGROUND: Depressive symptoms in mothers of young children can have serious
      consequences for the health of the child. In particular, children whose mothers
      are experiencing depressive symptoms are at significantly greater risk of
      poisoning and accidental injury. A mother's risk of developing depressive
      symptoms has been shown to be related to socio-economic disadvantage, high levels
      of stress and a perceived lack of social support. Residents who perceive their
      neighbourhoods to be of low social capital are more likely to report poor mental
      health. The aim of this study was to investigate the relationship between
      maternal depressive symptoms, deprivation, social support, stress and
      neighbourhood social capital in a group of mothers living in deprived areas of
      Nottingham, United Kingdom (UK). DESIGN AND SETTING: A postal questionnaire at
      entry to a randomised controlled trial (RCT) assessed socio-demographic
      characteristics and a second questionnaire, 21 months later, assessed depressive
      symptoms, perceived lack of social support, self-reported stress and individual
      level assessment of neighbourhood social capital. PARTICIPANTS: A total of 846
      mothers of young children living in deprived areas in Nottingham, UK, enrolled in
      the control group of an RCT. RESULTS: One-third of mothers reported high levels
      of depressive symptoms. Neighbourhood-level deprivation and receiving means
      tested benefits were independently associated with maternal depressive symptoms.
      A lack of social support and high levels of self-reported stress were also
      strongly associated with depressive symptoms. Individual-level assessment of
      neighbourhood social capital was not associated with depressive symptoms amongst
      mothers after adjusting for self-reported stress. CONCLUSIONS: Neighbourhood- and
      individual-level variables of deprivation and psychological distress are more
      important than mother's assessment of the social capital of the neighbourhood in
      which she lives in determining the risk of depressive symptoms. Interventions
      aimed at supporting mothers of young children may be more effective at reducing
      the risks of depressive symptoms and consequent risks to the child's health than
      interventions aimed at improving a neighbourhood's social capital.

PMID- 15742226
TI  - The Major Depression Inventory versus Schedules for Clinical Assessment in
      Neuropsychiatry in a population sample.
AB  - AIMS: This study examined the association between the Major Depression Inventory
      (MDI) and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN).
      METHODOLOGY: A questionnaire including the MDI was sent out to an adult
      population and was completed by a total of 10,448 persons. Psychiatrists used
      SCAN and interviewed a subsample (n=1093). RESULTS: The specificity of the MDI
      was 0.22, the sensitivity 0.67 and Kappa 0.25 when Major Depression according to
      SCAN was considered as the index of validity, and with all depressive disorders
      the specificity was 0.44, the sensitivity 0.51 and Kappa 0.33. Higher educated
      persons and those with reported disability were less likely to be false
      negatives. The sensitivity and specificity for different cut-off scores when
      using the MDI total score were calculated. CONCLUSION: The result from this study
      suggests that, when MDI is used in population-based samples, cut-off scores
      rather than the algorithm for depression should be used. The optimal cut-off
      score must be chosen according to the aims of the study.

PMID- 15742227
TI  - Social inequality and alcohol consumption-abuse in Bahia, Brazil-- interactions
      of gender, ethnicity and social class.
AB  - BACKGROUND: This paper reports findings on Alcohol Consumption-Abuse (ACAb) in
      Bahia, Brazil, a research setting characterized by racial/ethnic and
      socioeconomic diversity. METHODS: A household survey was conducted with a sample
      of 2,302 adults. ACAb was defined as daily intake of more than two units of
      beverage, with drunkenness, or weekly binge drinking plus episodes of
      drunkenness, or any use of alcoholic beverages with frequent drunkenness, with
      failed attempts to stop drinking. RESULTS: The rate of 12-month prevalence was
      7%, with an overall male: female ratio of 6:1. A positive association of ACAb
      prevalence with education and social class was found. Male gender and higher
      socio-economic status were associated with increased odds of ACAb. No
      relationship was found between ethnicity and ACAb. Stratified analysis yielded
      consistent gender effects, throughout all strata of independent variables. A
      strong interaction of gender (male) and social class (upper class) was found for
      Mulattos and Morenos (maximum Prevalence rate=9.04). CONCLUSION: Interaction
      patterns found defy simple generalizations based on class, ethnicity, and gender
      considered alone.

PMID- 15742228
TI  - Morale and job perception of community mental health professionals in Berlin and
      London.
AB  - INTRODUCTION: Morale and job perception of staff in community mental health care
      may influence feasibility and quality of care, and some research has suggested
      particularly high burnout of staff in the community. The aims of this study were
      to: a) assess morale, i. e. team identity, job satisfaction and burnout, in
      psychiatrists, community psychiatric nurses and social workers in community
      mental health care in Berlin and London; b) compare findings between the groups
      and test whether personal characteristics, place of working and professional
      group predict morale; and c) explore what tasks, obstacles, skills, enjoyable and
      stressful aspects interviewees perceived as important in their jobs. METHODS: In
      all, 189 mental health professionals (a minimum of 30 in each of the six groups)
      responded to a postal survey and reported activities per week using pre-formed
      categories. Perception of professional role was assessed on the Team Identity
      Scale, job satisfaction on the Minnesota Job Satisfaction Scale, and burnout on
      the Maslach Burnout Inventory. Seven simple open questions were used to elicit
      the main tasks, skills that staff did and did not feel competent in, aspects that
      they did and did not enjoy in their job, and obstacles and factors that caused
      pressure. Answers were subjected to content analysis using a posteriori formed
      categories. RESULTS: Weekly activities and morale varied between sites and
      professional groups. Some mean scores for groups in London exceeded the threshold
      for a burnout syndrome, and are particularly less favourable for social workers.
      Working in London predicted higher burnout, lower job satisfaction and lower team
      identity. Being a psychiatrist predicted higher team identity, whilst being a
      social worker was associated with higher burnout and lower job satisfaction. Male
      gender predicted lower burnout and higher team identity. However, professional
      group and site interacted in predicting burnout and job satisfaction.
      Psychiatrists in London had much more favourable scores than the other two
      groups, whilst this did not hold true in Berlin. Answers to open questions
      revealed universal aspects, such as enjoying direct patient contact and disliking
      bureaucracy, but also various views that were specific to a site or professional
      group or both. CONCLUSIONS: Burnout remains a problem for some, but not all,
      professional groups in community mental health care, and social workers in London
      appear to be a group with particularly low morale. Differences between
      professional groups depend on the location, and it remains unclear to what extent
      job-related and general factors impact on the morale of mental health
      professionals. Answers to open questions reveal general as well as specific
      aspects of the job perception of the professional groups, some of which may be
      relevant for service development, training and supervision. More conceptual and
      methodological work and more extensive studies are required to develop a better
      understanding of how community mental health professionals perceive their job and
      how morale may be improved.

PMID- 15742229
TI  - Structure of needs among persons with schizophrenia.
AB  - BACKGROUND: The importance of needs assessment for service development has been
      widely recognised. Several studies have focused on the associations between
      ratings of needs by patients and staff and have found clear differences,
      especially concerning the unmet needs. METHODS: The present study is part of a
      Nordic Multicentre study that investigates the life and care of outpatients with
      a schizophrenia group illness in all the Nordic countries. The aim of this paper
      is to study the patterns of needs as identified by patients and staff according
      to the Camberwell Assessment of Needs (CAN). Quality of life, level of
      functioning, and psychiatric symptoms were assessed. RESULTS: The sample includes
      300 patients, 194 (65%) men and 106 (35%) women. The factor analysis identified
      five factors for patients and four factors for staff in the questionnaire on
      ratings of needs. In four of the five patient-related factors a meaningful
      interpretation was possible, and the factors were named skills, illness, coping,
      and substance abuse. The staff-related factors were named skills, impairment,
      symptom, and substance abuse. There were significant associations between the sum
      scores constructed from the factors and measures of functioning level and
      symptoms. CONCLUSIONS: It seems that the sum factor reflecting secondary needs
      was the most important of the identified factors among both patient and staff
      ratings. The item-by-item comparisons in previous studies have emphasised
      differences between patient and staff ratings, but our analysis of the structure
      of needs also found similarities in the structures and in the associations
      between the identified sum scores and measures of symptoms, functioning level,
      and quality of life.

PMID- 15742230
TI  - Panic attacks as risk markers for mental disorders*.
AB  - OBJECTIVE: This paper extends previous epidemiological findings linking panic
      attacks with future episodes of depression and examines whether this relationship
      is independent of the effects of gender and neuroticism. METHODS: Composite
      International Diagnostic Interview (CIDI) DSM-IV diagnoses from a stratified
      multi-stage population survey of 10,641 Australian adults were analysed using
      logistic regression to examine the relationship between lifetime panic attacks,
      gender, neuroticism and mental disorders. RESULTS: People who experienced full
      CIDI DSM-IV panic attacks more than 12 months ago were 4 times more likely to
      meet criteria for current Depressive Disorder than those who reported no attacks.
      Those with panic attacks in the past 12 months were 13.3 times more likely to
      report current Depressive Disorders. A similar pattern was also present for non
      panic Anxiety Disorders (odds ratio=7.5 for lifetime, but not 12-month panic
      attacks, and 21.46 for 12-month panic attacks) and for Substance Use Disorders
      (2.1 and 4.6, respectively) suggesting a broader relationship with
      psychopathology than previously reported. For each of these groupings of mental
      disorders, panic attacks accounted for significant variability over and above the
      effects of gender, neuroticism, and comorbid Anxiety Disorders. CONCLUSIONS:
      Panic attacks are associated with current and future Anxiety, Depressive, and
      Substance Use Disorders, and this relationship is not solely accounted for by
      differences in gender and neuroticism.

PMID- 15742231
TI  - An innovative and reliable way of measuring health-related quality of life and
      mental distress in the deaf community.
AB  - BACKGROUND: Structured assessment of quality of life and mental distress in deaf
      people is difficult for various reasons. This paper describes the development and
      reliability of an interactive computer-based assessment package for measuring
      quality of life and psychological distress in the deaf population. METHODS: The
      Brief version of the WHO Quality of Life (WHOQOL) Questionnaire, the 12-item
      General Health Questionnaire (GHQ-12) and the Brief Symptom Inventory (BSI) had
      been translated into sign-language and videotaped. A total of 236 members of the
      deaf community in Upper Austria participated by responding to a programme
      consisting of self-administered written and videotaped test-items presented to
      them on a notebook computer. The reliability of the various assessments was
      established on this large community sample. RESULTS: When reliability of the
      versions for the deaf was compared with that of written versions of the same
      measures in general population samples, it was found to be somewhat lower,
      although still in an acceptable range, for the WHO-QOL and the GHQ-12. For the
      BSI, the reliability was even higher than that of the general population.
      CONCLUSIONS: For deaf individuals whose preferred communication is sign language,
      quality of life and mental distress can be effectively and reliably assessed with
      the use of carefully translated and adapted common instruments.

PMID- 15742232
TI  - Vitamin E provides protection for bone in mature hindlimb unloaded male rats.
AB  - The deleterious effects of skeletal unloading on bone mass and strength may, in
      part, result from increased production of oxygen-derived free radicals and
      proinflammatory cytokines. This study was designed to evaluate the ability of
      vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory
      properties, to protect against bone loss caused by skeletal unloading in mature
      male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb
      unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg
      diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet)
      vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on
      bone, dietary treatments were initiated 9 weeks prior to unloading and continued
      during the 4-week unloading period, at which time animals were euthanized and
      blood and tissue samples were collected. Serum vitamin E was dose-dependently
      increased, confirming the vitamin E status of animals. The HD treatment improved
      oxidation parameters, as indicated by elevated serum ferric-reducing ability and
      a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of
      the distal femur revealed significant reductions in trabecular thickness (TbTh),
      double-labeled surface (dLS/BS), and rate of bone formation to bone volume
      (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had
      reduced bone surface normalized to tissue volume (BS/TV) and trabecular number
      (TbN); however, the HD vitamin E protected against these changes in the HU
      animals. Our findings suggest that vitamin E supplementation provides modest bone
      protective effects during skeletal unloading.

PMID- 15742233
TI  - Mechanical properties of femoral diaphysis and femoral neck of female rats
      chronically exposed to various levels of cadmium.
AB  - The effect of chronic exposure to cadmium (Cd) on the mechanical properties of
      femoral diaphysis and femoral neck was investigated on a rat model of human
      exposure. Three-week-old female Wistar rats were exposed to Cd in drinking water
      at concentrations of 1, 5, 50, or 100 mg/L for 12 months. Biomechanical
      properties of the femoral diaphysis were evaluated in a three-point bending test
      and those of the femoral neck in a bending test with vertical loading of the
      head. Bone mineral content (BMC) and bone mineral density (BMD) at the whole
      femur, and BMD at the diaphysis and proximal femur (head and neck region) of the
      Cd-treated rats decreased in a dose-dependent manner, except for the diaphyseal
      BMD at a Cd concentration of 1 mg/L. Exposure to Cd concentrations of 1 and 5
      mg/L had only little effect on the diaphyseal mechanical properties (decreased
      yield load with unchanged bending strength, stiffness, yield stress, ultimate
      stress, and Young modulus), whereas the bending strength and stiffness of the
      neck decreased and the yield load clearly tended to decline or declined. The
      effect of Cd at the two locations was more marked in the 50 and 100 mg/L groups,
      and changes in the bone geometry were observed in these animals. The results
      clearly revealed that chronic, even low-level, exposure to Cd results in
      demineralization and weakening of the femur. The femoral neck seems to be more
      vulnerable than the diaphysis to failure from Cd. We conclude that environmental
      exposure to Cd may be an important risk factor for femoral neck fracture.

PMID- 15742234
TI  - Bone chemical structure response to mechanical stress studied by high pressure
      Raman spectroscopy.
AB  - While the biomechanical properties of bone are reasonably well understood at many
      levels of structural hierarchy, surprisingly little is known about the response
      of bone to loading at the ultrastructural and crystal lattice levels. In this
      study, our aim was to examine the response (i.e., rate of change of the
      vibrational frequency of mineral and matrix bands as a function of applied
      pressure) of murine cortical bone subjected to hydrostatic compression. We
      determined the relative response during loading and unloading of mineral vs.
      matrix, and within the mineral, phosphate vs. carbonate, as well as proteinated
      vs. deproteinated bone. For all mineral species, shifts to higher wave numbers
      were observed as pressure increased. However, the change in vibrational frequency
      with pressure for the more rigid carbonate was less than for phosphate, and
      caused primarily by movement of ions within the unit cell. Deformation of
      phosphate on the other hand, results from both ionic movement as well as
      distortion. Changes in vibrational frequencies of organic species with pressure
      are greater than for mineral species, and are consistent with changes in protein
      secondary structures such as alterations in interfibril cross-links and helix
      pitch. Changes in vibrational frequency with pressure are similar between loading
      and unloading, implying reversibility, as a result of the inability to
      permanently move water out of the lattice. The use of high pressure Raman
      microspectroscopy enables a deeper understanding of the response of tissue to
      mechanical stress and demonstrates that individual mineral and matrix
      constituents respond differently to pressure.

PMID- 15742235
TI  - Measurement of estrogen effect on bone turnover by 2H2O labeling.
AB  - Estrogen loss has been known to increase bone turnover through accelerated bone
      resorption coupled by increased bone formation. In the present study, we measured
      estrogen effect on bone turnover by incorporation of 2H from 2H2O into amino
      acids. At 6 weeks of age, rats were either sham-operated (sham) or ovariectomized
      (ovx). Two weeks after surgery, 17beta-estradiol (est) was implanted
      subcutaneously to ovx rats. At 9 weeks of age, 2H2O labeling started by
      administration of 4% 2H2O to rats for 4 or 7 weeks in drinking water after a
      single intraperitonial bolus injection with 99.9% 2H2O. Body 2H2O enrichments
      were stable at approximately 3.0% over labeling period. Fractional replacements
      (f) of the midshaft femur were higher in the sham group (40.36 +/- 4.89% vs 42.47
      +/- 11.22%) than the ovx (28.57 +/- 9.67% vs 37.47 +/- 8.34%) and est (26.57 +/-
      4.00% vs 30.35 +/- 5.34%) groups 4 and 7 weeks after labeling, respectively.
      Ovariectomy-induced bone loss was observed in the trabecular bone along with a
      significantly increased number of osteoclasts, all of which were normalized after
      estradiol treatment. Taken together, our results indicate that estrogen
      deficiency significantly reduces the proportion of newly synthesized bone matrix
      as well as the total amount of bone matrix. The reduced portion of new matrix in
      ovx rats, presumably caused by activated osteoclastic degradation, was
      compensated rapidly with time. In addition, estradiol treatment protected the
      bone matrix by decreasing bone turnover rate.

PMID- 15742237
TI  - Temperature-dependent genome degradation in the coccoid form of Campylobacter
      jejuni.
AB  - Campylobacter jejuni undergoes a dramatic morphological transformation from a
      corkscrew-shaped rod to a coccoid form in response to unfavorable conditions. It
      has been speculated that the coccoid plays an important role in the survival and
      dissemination of C. jejuni but questions still remain regarding the viability of
      coccoid cells. Characterization of the genome of coccoid cells found that newly
      formed coccoid cells (i.e., 1-3 days) had a SmaI-digestion profile identical to
      that of spiral-shaped cells; however, there was a progressive degradation of the
      DNA with continued incubation at 37 degrees C. Concomitant with genome
      degradation was the detection of DNA in supernatants of coccoid cells. In
      contrast, cells incubated at 4 degrees C retained a spiral shape and their SmaI
      digestion profile for 8 weeks and released little DNA into the medium. Thus, low
      temperature inhibited both coccoid formation and genome degradation.
      Collectively, these data support the theory that the coccoid form of C. jejuni is
      a manifestation of cellular degradation and spiral-shaped cells, or possibly
      coccoid cells formed at low temperature, are the most probable candidates for a
      viable but nonculturable form of this pathogen.

PMID- 15742238
TI  - Prevalence of exercise-induced bronchospasm in long distance runners trained in
      cold weather.
AB  - We investigated whether regular training in cold weather has an effect on the
      development of exercise-induced bronchospasm. Nineteen sedentary males and 20
      male long distance runners who were regularly training in Erzurum participated in
      this study. They had no history of asthma, atopy or allergic rhinitis. Pre- and
      post-exercise spirometry was performed in the participants in room temperature.
      EIB was defined as at least a > or =10% fall in FEV1 or a > or =15% fall in
      FEF(25-75%) or a > or =25% fall in PEFR. EIB was established in 7 of 20 athletes
      and in 1 of 19 sedentaries. Prevalence of EIB will be higher even if it is
      established in room temperature when training for the sports like long distance
      running which is not a cold weather sport. We conclude that it will be more
      convenient to establish EIB in room temperature and in the laboratory since the
      exercise test and spirometry can be performed more accurately under more standard
      conditions.

PMID- 15742239
TI  - Characterization of functional, radiologic and lung function recovery post
      treatment of hot tub lung. A case report and review of the literature.
AB  - Hot tub lung is described as an acute pulmonary illness that is characterized by
      fever, dyspnea and interstitial nodular infiltrates. Although not entirely clear,
      the etiology may be a hypersensitivity pneumonitis, an infection secondary to
      Mycobacterium avium intracellulare (MAC), or possibly both. Herein we describe
      the most well-characterized physiologic, radiographic, and functional recovery
      from hot tub lung reported in the literature to date. Pulmonary function testing
      and CT scans of the chest were obtained after each therapeutic intervention, and
      the patient had the most dramatic improvement with simply avoiding the hot tub.
      Prednisone therapy offered minimal further improvement while anti-MAC therapy
      provided no further improvement. These results are suggestive of a
      hypersensitivity pneumonitis rather than an infectious etiology.

PMID- 15742240
TI  - Treatment of atopic cough caused by Basidiomycetes antigen with low-dose
      itraconazol.
AB  - We report two patients with atopic cough due to Basidiomycetes antigen. One
      patient was a 27 year-old woman and the other was a 17 year-old boy. Both
      patients visited our hospital because of severe nonproductive cough. They did not
      have bronchial hyperresponsiveness to methacholine or heightened bronchomotor
      tone. Bronchodilator therapy was not effective for their cough. Her symptoms
      worsened in her office and his in his house, suggesting existence of etiologic
      agent(s) in their environments. Basidiomycetes was isolated from the woman's
      office and from the boy's house, and the bronchoprovocation test with
      Basidiomycetes antigen was positive. Low dose itraconazol (50 or 100 mg/day)
      given for two weeks eliminated cough in both patients. This is the first report
      describing the effectiveness of low dose antifungal therapy for atopic cough
      caused by Basidiomycetes antigen.

PMID- 15742241
TI  - A preliminary study of PEFR monitoring in patients with chronic cough.
AB  - It is important to make a differential diagnosis of cough variant asthma in
      patients with chronic cough. To examine whether or not peak expiratory flow rate
      (PEFR) is useful for the differential diagnosis of cough variant asthma in such
      patients, diurnal variation rates of PEFR were calculated in 23 patients who
      presented with dry cough lasting four or more weeks and who showed no
      abnormalities on chest radiographs. None of the patients had wheezes, and
      pulmonary function testing at the time of visit to the hospital revealed no
      abnormalities. During the control period, the mean diurnal variation rate of PEFR
      in 23 patients was 16.3 +/- 7.9%. Six, nine and eight patients had PEFR diurnal
      variations rates of <10% (Group 1), 10-19% (Group 2), and > or = 20% (Group 3),
      respectively. At week 3 of treatment with bronchodilators, only Group 3 showed a
      significant decrease in PEFR diurnal variation rate from 25.7% to 10.1%. The
      cough score decreased significantly in Group 3 only. These patients had enhanced
      bronchial hyperresponsiveness and showed eosinophils in induced sputum, leading
      to the diagnosis of cough variant asthma (CVA). After making the diagnosis of
      CVA, an inhaled corticosteroid or a Th2 cytokine production inhibitor suplatast
      tosilate was administered to patients; consequently, they showed no recurrence of
      cough. PEFR monitoring allowed the detection of morning dip and was suggested to
      be potentially useful for the differential diagnosis of cough variant asthma in
      patients with chronic cough.

PMID- 15742243
TI  - Research agenda on the risk and prevention of falls: 2002-2007.

PMID- 15742244
TI  - What is next for locomotor-based studies?

PMID- 15742242
TI  - Innate host defense of the lung: effects of lung-lining fluid pH.
AB  - Lung-lining fluid (LLF) is a primary constituent of the pulmonary host defense
      system. It is distributed continuously throughout the respiratory tract but is
      heterogeneous regarding its chemistry and physiology between the conducting
      airways and alveoli. The conducting airways are lined with airway surface liquid
      (ASL), a mucus gel-aqueous sol complex that interacts functionally with
      epithelial cilia as the mucociliary escalator. The alveoli are lined with
      alveolar subphase fluid (AVSF) and pulmonary surfactant. AVSF sterility is
      maintained in part by the phagocytic activity of resident alveolar macrophages.
      Normal ASL and AVSF are both more acidic than blood plasma. However, the details
      of acid-base regulation differ between the two media. Appreciable transepithelial
      acid-base flux is possible across the airway epithelium, whereas the alveolar
      epithelium is relatively impermeable to transepithelial acid-base flux. Moreover,
      one must consider the influence of resident macrophages on AVSF pH. Resident
      macrophages occupy a sizable fraction of AVSF by volume and are a substantial
      source of metabolic H+. The buffering capacities of ASL and AVSF probably are
      largely due to secreted peptides (e.g., ASL mucins and AVSF surfactant proteins).
      Acid-base exchange between the extracellular hydrophase and intracellular
      buffering systems of resident macrophages represents an additional buffer pool
      for AVSF. The pH of ASL and AVSF can be depressed by disease or inflammation. Low
      pH is predicted to suppress microbe clearance from the airways and alveoli,
      increase pathogen survival in both regions, and alter mediator release by
      resident macrophages and recruited leukocytes thereby increasing the propensity
      for bystander cell injury. Overall, ASL/AVSF pH is expected to be a major
      determinant of lung host defense responses.

PMID- 15742246
TI  - A measure of neurobehavioral functioning after coma. Part II: Clinical and
      scientific implementation.
AB  - This is a longitudinal validation study that is Part II of a two-part series.
      Part I focuses on the methods used to construct the neurobehavioral measure
      derived from the Disorders of Consciousness Scale (DOCS) as well as the evidence
      of reliability and validity. Part II illustrates, through a series of selected
      case reports, the clinical use of repeated DOCS measures to enhance and
      complement medical rehabilitation management. The use of repeated DOCS measures
      in scientific investigations of mechanisms of injury is also described.
      Participants included patients at rehabilitation hospitals who were 18 years of
      age and older and unconscious after severe brain injury. Medical decision making
      regarding short-term effects of pharmacological intervention was augmented and
      improved through the examination of individual neurobehavioral recovery patterns.
      We identified medications to treat secondary medical complications and
      successfully determined effective dosage, presumably improving prognosis for
      recovery. We facilitated and enhanced development and refinement of
      individualized rehabilitation programs. Two investigations of treatment
      effectiveness during coma recovery and examination of the relationship between
      behavioral changes and neural adaptation are also described. By systematically
      tracking and mapping individual patterns of neurobehavioral recovery, we show
      that medical and rehabilitation management after coma can be enhanced. In
      addition, we also show that by examining the relationship between the DOCS
      neurobehavioral measure with mechanistic indicators of neurological recovery such
      as functional magnetic resonance imaging, scientific investigations of treatment
      and rehabilitation effectiveness can be enhanced.

PMID- 15742245
TI  - A measure of neurobehavioral functioning after coma. Part I: Theory, reliability,
      and validity of Disorders of Consciousness Scale.
AB  - This is longitudinal validation study describes the psychometric properties of
      the Disorders of Consciousness Scale (DOCS). This is Part I of a two-part series.
      Part II illustrates and describes the clinical and scientific implementation of
      the DOCS measure. The study was conducted at one intensive care unit, two acute
      rehabilitation hospitals, and one long-term acute chronic care hospital.
      Participants were unconscious after severe brain injury (BI). We conducted
      interrater reliability analyses using ratings from interdisciplinary pairs.
      Results indicated a higher-than-expected level of agreement and no significant
      difference between any pairs ( chi-square = 8(5df), p = 0.15) (df = degrees of
      freedom). Examinations of ratings by discipline groups indicated that the DOCS is
      impacted minimally by discipline. Validity analyses demonstrate that 23 of 34
      test stimuli remain stable over time with no floor or ceiling effect. DOCS
      measures obtained within 94 days of injury predicted recovery of consciousness up
      to 1 year after injury (c-indices of 0.70 and 0.86). Positive (0.71) and negative
      (0.68) predictive values indicate that the DOCS predicts recovery and lack of
      recovery. Twenty-three of the DOCS test stimuli produce a reliable, valid, and
      stable measure of neurobehavioral recovery after severe BI that predicts recovery
      and lack of recovery of consciousness 1 year after injury.

PMID- 15742247
TI  - Event-related potential in facial affect recognition: potential clinical utility
      in patients with traumatic brain injury.
AB  - Traumatic brain injury (TBI) frequently leads to deficits in social behavior.
      Prior research suggests that such deficits may result from impaired perception of
      basic social cues. However, these social-emotional deficits have not been studied
      electrophysiologically. We measured the P300 event-related potential (ERP), which
      has been shown to be a sensitive index of cognitive efficiency, in 13 patients
      with a history of moderate to severe TBI and in 13 healthy controls. The P300
      response was measured during detection of 30 pictures of angry faces (rare
      target) randomly distributed among 120 neutral faces (frequent nontarget).
      Compared to control subjects, the TBI group's P300 responses were significantly
      delayed in latency (p = 0.002) and lower in amplitude (p = 0.003). TBI patients
      also showed slower reaction times and reduced accuracy when manually signaling
      their detection of angry faces. Coefficients of variation (CV) for the facial
      P300 response compared favorably to those of many standard clinical assays,
      suggesting potential clinical utility. For this study, we demonstrated the
      feasibility of studying TBI patients' P300 responses during the recognition of
      facial affect. Compared to controls, TBI patients showed significantly impaired
      electrophysiological and behavioral responses while attempting to detect
      affective facial cues. Additional studies are required for clinicians to
      determine whether this measure is related to patients' psychosocial function in
      the community.

PMID- 15742248
TI  - The Indianapolis Vocational Intervention Program: a cognitive behavioral approach
      to addressing rehabilitation issues in schizophrenia.
AB  - Despite wishing to return to productive activity, many individuals with
      schizophrenia enter rehabilitation with severe doubts about their abilities.
      Negative beliefs in schizophrenia have been linked with poorer employment
      outcome. Accordingly, in this paper, we describe efforts to synthesize vocational
      and cognitive behavior therapy interventions into a 6-month manualized program to
      assist persons with schizophrenia spectrum disorders overcome negative beliefs
      and meet vocational goals. This program, the Indianapolis Vocational Intervention
      Program (IVIP), includes weekly group and individual interventions and is
      intended as an adjunct to work therapy programs. The IVIP was initially developed
      over a year of working with 20 participants with Structured Clinical Interview
      for the Diagnostic and Statistical Manual-I (SCID-I) confirmed diagnoses of
      schizophrenia or schizoaffective disorder who were actively engaged in 20 hours
      per week of work activity. For this paper, we explain the development of the
      treatment manual and the group and individual interventions and present case
      examples that illustrate how persons with severe mental illness might utilize the
      manualized intervention.

PMID- 15742249
TI  - Rehabilitation following stroke in patients aged 85 and above.
AB  - To assess the course and results of rehabilitation following stroke in the oldest
      old, we conducted a prospective study to compare 45 patients 85 years and above
      and 220 consecutive patients aged 75 to 84 years who were hospitalized for
      rehabilitation following stroke. Functional status was measured and compared by
      the Functional Independence Measuretrade mark(FIM) scale and successful
      rehabilitation was defined as FIM > 80 at discharge. Eighteen patients in the 85+
      group (40%) underwent successful rehabilitation compared with 115 (52%) in the 75
      to 84 group (not significant). No significant differences were found between the
      groups in any other parameters that measure success and/or efficacy of
      rehabilitation, but in all these parameters, without exception, there were lower
      values in the 85+ group. No differences in the length of rehabilitation and
      complications rates were found between groups. We conclude that although the
      success rate for rehabilitation following stroke is lower in the oldest old, it
      appears that the effort invested in rehabilitating patients in this group is no
      less justified than in younger elderly patients.

PMID- 15742250
TI  - A validity study of phase velocity measurements in spinal cord injury.
AB  - We measured a cross-section of able-bodied (AB) men (n = 175) and men with
      chronic spinal cord injury (SCI) (n = 33) residing in the community, 14 to 65
      years old, to identify associations between dietary factors, physical activity,
      health status, and mechanical properties of long bones assessed by phase velocity
      measurement of flexural waves in the tibia during the second to seventh decades.
      This study (1) evaluated the influence of different types of osteoporosis risk
      factors on measured phase velocity of tibia bone as measured by Bone Stiffness
      Measurement Device (BSMD)-Swing in AB men and in men with long-standing SCI and
      (2) estimated the construct validity of phase velocity measurements by assessing
      the discriminatory capability of the BSMD-Swing. Linear regression analysis
      suggests a direct relationship between health status, tibia length, age, and
      phase velocity (R(2) = 23%). An analysis of variance results in significant
      differences in phase velocity values between AB controls and individuals with SCI
      with and without pathologic fracture history. Phase velocity measurements in the
      tibia shaft provide useful information about bone status in populations at risk
      for low-trauma fractures and seems well suited for assessing tibia bone status in
      SCI.

PMID- 15742251
TI  - Upper-limb function and recovery in the acute phase poststroke.
AB  - This study evaluates stroke patients with upper-limb (UL) motor deficits using
      measures of impairment and "activity limitation" to quantify recovery of UL
      function poststroke and to identify predictors of UL function and predictors of
      UL recovery following stroke. The study also compares the recovery of UL function
      with that of the lower limb (LL). Measures of impairment and "activity
      limitation" of the UL and LL improved over the first 5 weeks. The Box and Block
      Test performance improved the most over 5 weeks (standardized response mean [SRM]
      = 1.34), followed closely by the 5-meter walk test (SRM = 0.97). Performances on
      measures of UL "activity limitation" measured at 1 week poststroke were the most
      important predictors of UL function 5 weeks poststroke. The results of this study
      do not support the belief that recovery of LL function is faster than that of UL.

PMID- 15742252
TI  - Development of an integrated stroke outcomes database within Veterans Health
      Administration.
AB  - A fundamental goal of the Rehabilitation Outcomes Research Center of Excellence
      is to improve care and outcomes for veterans with rehabilitation needs. To
      achieve this goal, the Center's primary objective is increasing research
      capacity. The Integrated Stroke Outcomes Database is a collection of Veterans
      Health Administration (VHA) clinical and administrative data containing patient
      information on a cohort of stroke patients found in the Functional Status
      Outcomes Database (FSOD), National Patient Care Database (NPCD), and other VHA
      sources. Clinical and administrative data were abstracted from several VHA data
      sources and linked to form an integrated outcomes database. A primary cohort of
      stroke patients treated during fiscal year (FY) 2001 was identified from the
      FSOD. Matching data from the NPCD, Decision Support System, Health Economics
      Resource Center, and the National Veterans Survey were obtained, merged, and
      reported in brief. This integrated database structure will provide valuable
      support to enhance the VHA capacity to perform stroke rehabilitation research.

PMID- 15742253
TI  - Active treatments for aprosodia secondary to right hemisphere stroke.
AB  - This study investigates the effects of two mechanism-based treatments for
      expressive aprosodia. Three participants, two women and one man, had a right
      hemisphere cerebral infarction resulting in affective aprosodia with greater
      expressive than receptive deficits. Trained raters determined presence of
      aprosodia by judging participants' performance on two emotional communication
      batteries. A single-subject design with replication across three participants was
      employed. Sentence production with the use of treated and nontreated emotions was
      measured during baseline and treatment phases. Sentences were scored for accuracy
      by a trained rater blind to time of testing and analyzed visually and
      statistically. Effect sizes calculated on the resulting data for each participant
      and treatment confirmed modest to substantial treatment effects for both
      treatments in all three participants. Because of a relative paucity of treatment
      studies investigating expressive aprosodia, these data are among the first to
      suggest that aprosodia may be amenable to behavioral treatments.

PMID- 15742255
TI  - Short-term timecourse of bilateral pudendal nerve injury on leak-point pressure
      in female rats.
AB  - The pudendal nerve innervates the external urethral sphincter and, when injured,
      can contribute to incontinence development. This experiment was designed to study
      the time course of functional changes in the urethra after pudendal nerve crush
      in rats. Leak-point pressure (LPP) was measured 2, 4, 7, or 14 days after
      bilateral pudendal nerve crush and was compared to that of a control group. LPP
      at all four time points after nerve injury was significantly decreased compared
      to control values. A minimum was reached 4 days after injury, and LPP appeared to
      trend upward with increasing time after injury, suggesting that nerve function
      may begin to recover or compensatory changes in the urethra may occur. Pudendal
      nerve crush induces decreased LPP in female rats, mimicking the clinical symptoms
      of stress incontinence. When fully characterized, this model could be useful for
      preclinical testing of treatment and rehabilitation protocols.

PMID- 15742254
TI  - Comparison of the 2-, 6-, and 12-minute walk tests in patients with stroke.
AB  - This study assessed inter- and intrarater reliability and sensitivity to change
      of the 2-, 6-, and 12-minute walk tests following stroke. A convenience sample of
      patients enrolled in an inpatient stroke rehabilitation program participated in
      the standardization protocol. The 2-, 6-, and 12-minute walk tests were performed
      and inter- and intrarater reliability and responsiveness to change assessed. The
      interrater intraclass correlation coefficients (ICCs) for the 2-, 6-, and 12
      minute walk tests were, respectively, 0.85, 0.78, and 0.68 (p < 0.0007 for each).
      The intrarater ICCs were 0.85, 0.74, and 0.71 (p < 0.0003 for each).
      Responsiveness to change as measured by standardized response mean (SRM) scores
      was, respectively, 1.34, 1.52, and 1.90 (F = 24.24, p < 0.001). Pearson
      correlations for the 2-, 6-, and 12-minute walk tests by the same rater on the
      same day were 2 versus 6 minutes, r = 0.997; 2 versus 12 minutes, r = 0.993; and
      6 versus 12 minutes, r = 0.994 (p < 0.0001 for each). The 2-, 6-, and 12-minute
      walk tests show acceptable inter- and intrarater reliability and high intertest
      correlations when they are used for the assessment of walking following stroke.
      The SRM statistic indicates that the 12-minute walk test is the most responsive
      to change.

PMID- 15742256
TI  - Quality of life in male tracheoesophageal (TE) speakers.
AB  - For this study, we determined the quality of life (QOL) in individuals who had
      undergone total laryngectomy (TL) and who used tracheoesophageal (TE) speech as
      their primary method of postlaryngectomy communication. We also descriptively
      compared present QOL outcomes with those found in an extension of the Department
      of Veterans Affairs' (VA) Laryngeal Cancer Study. Thirty laryngectomized men with
      TE speech as their primary mode of communication were recruited for participation
      in the investigation. Participants completed a general information form as well
      as the University of Michigan Head and Neck Quality of Life (HNQOL) instrument.
      Results revealed a high level of self-perceived QOL in the domains of
      communication, eating, pain, and emotion that was empirically better than results
      found in a previous study involving individuals who had undergone TL and who were
      treated in VA hospitals. Possible reasons for the improved self-reported QOL
      among individuals in the present group include use of TE speech for
      postlaryngectomy communication, a higher level of education, and membership in a
      support group. The results suggest to us that these factors should be considered
      in postlaryngectomy care in the veteran population to optimize rehabilitation
      outcomes.

PMID- 15742257
TI  - Prognostic significance of G1 cell-cycle inhibitors in early laryngeal cancer.
AB  - BACKGROUND: Radiation therapy yields a 2-year local control rate of 80% to 90% in
      early laryngeal squamous cell carcinoma. However, a subset of early laryngeal
      cancers has a significantly higher rate of local recurrence and lower rate of
      overall survival. OBJECTIVE: The objective of this study was determine the
      prognostic significance of p53, p27, and p21 expression in patients with early
      laryngeal cancer. METHODS: Expression of p53, p27, and p21 proteins in
      pretreatment biopsies from sixty-eight patients was analyzed by using
      immunohistochemistry. Low (</=10% cells) and high (>10% cells) levels of
      expression were measured. All patients were newly diagnosed and treated with
      external beam radiation. Other contributing factors were also studied, such as
      age, sex, race, tumor site, and stage. RESULTS: Forty (58.8%) and 28 (41.2%)
      lesions were staged as T1 and T2, respectively, whereas 16 (23.5%) and 52 (76.5%)
      were located in the supraglottis and glottis, respectively. Overexpression of
      p27, p53, and p21 was found in 36.7%, 60.6%, and 60% of cases, respectively.
      Overexpression of p27 was found to be a significant predictor of recurrence by
      multivariate analysis (RR 3.3, P = .017). Overexpression of p21 and/or p53 was
      not predictive of recurrence. No factor predicted disease specific or nonspecific
      overall survival. CONCLUSION: Our results indicate the significance of p27
      overexpression as an indicator of recurrence in patients with early laryngeal
      squamous cell carcinoma.

PMID- 15742258
TI  - Lateral minimal parathyroidectomy: safety and cosmetic benefits.
AB  - BACKGROUND: Surgery has been the cornerstone of treatment for primary
      hyperparathyroidism for almost three decades. The recent application of state-of
      the art imaging technologies to localize hyperfunctioning adenomas preoperatively
      has enabled surgeons to minimize the surgical procedure, reduce total operation
      time and improve cosmetic results without compromising the cure rate. STUDY
      DESIGN: Twenty-one patients with a diagnosis of primary hyperparathyroidism were
      selected for treatment with the lateral minimal parathyroidectomy approach
      following preoperative imaging with ultrasonography, Tc-sestamibi scan, or both.
      All patients were followed during hospitalization and for three months after for
      calcium levels and cosmetic results. RESULTS: The procedure was performed by the
      same surgical team for all 21 patients; under general anesthesia in 20 patients
      and under deep sedation in 1 patient at high surgical risk. In all cases,
      parathyroid adenoma was accurately localized by at least one of the imaging
      modalities before surgery: ultrasonography in 16 patients (76%), Tc-sestamibi
      scan in 15 (71%), and both in 10 (48%). Average total operative time for the
      lateral minimal invasive approach was 46 minutes (range 30-65 minutes). Blood
      calcium levels returned to normal in all patients, and cosmetic results were
      graded good to excellent. CONCLUSIONS: With accurate preoperative localization of
      unilateral parathyroid adenoma by any imaging modality and careful patient
      selection, lateral minimal parathyroidectomy performed by a skilled surgeon may
      serve as a safe, effective procedure with good clinical and aesthetic outcomes.

PMID- 15742259
TI  - Occult papillary thyroid carcinoma in postmortem species: prevalence at autopsy.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of occult
      papillary thyroid cancer (OPTC) in a sample of cadavers from Guatemala, a country
      in Central America. STUDY DESIGN AND SETTING: This was a cross-sectional study of
      cadaver samples. We analyzed 150 glands that were removed during autopsy from 150
      cadavers (34 women and 116 men) who were admitted to the morgue of the Judicial
      Bureau between January and March 2000. RESULTS: A total of 17 glands showed
      macroscopic evidence of disease, but only 3 glands (1 female and 2 males) showed
      microscopic evidence of malignancy. This corresponded to a 2% prevalence rate
      (range, 0.4-5.7%). The sex prevalence of OPTC was 2.9% (range, 0.07-15%) for
      females and 1.7% (range, 0.2-6.1%) for males. No significant difference was noted
      ( P = .47, exact unconditional test). The male-to-female ratio was 1:1.7.
      CONCLUSION: We concluded that the prevalence of OPTC in Guatemala is low but
      comparable to literature reports. Occult papillary thyroid carcinoma appears to
      have no sex predilection as opposed to the clinically evident papillary thyroid
      carcinoma, which develops more commonly in females. SIGNIFICANCE: Occult
      papillary thyroid carcinoma is a much more common pathology than clinically
      evident thyroid cancer, and the clinical implications still need to be
      determined.

PMID- 15742260
TI  - Vestibular cytotoxicity in gentamicin-treated frogs: a preliminary report.
AB  - OBJECTIVE: The aim of this study is to determine the immediate effects of
      intraperitoneal doses of gentamicin (GM) which would result in variable degrees
      of destruction of crista ampullary hair cells of frogs. This information will
      serve as a baseline guide to cell regeneration experiments on the damaged
      vestibular sense organ. STUDY DESIGN: The American bullfrog was administered
      daily intraperitoneal doses of 50, 100, 150, and 200 mg/kg of GM for 7 days.
      Animals were sacrificed 1 day after the final injection for cytomorphic
      evaluation. Histologically processed posterior semicircular duct cristae were
      resin-embedded, and tissue samples were subjected to serial cross sectioning of
      the crista from the periphery to the central zone using glass knives in an
      ultramicrotome. Stained sections were analyzed in light microscope using ocular
      grid micrometry. The areal density of nuclear profiles of the vestibular sensory
      and supporting cells (sensory cells [SNCs] and supporting cells [SPCs],
      respectively; number per square millimeter) and the nuclear diameter of SNCs were
      manually determined. RESULTS: A 7-day administration of GM produced noticeable
      quantitative alteration of the posterior crista hair cells and SPCs. Histological
      analysis revealed a significant decrease in the density of SNCs and a concomitant
      increase in the density of SPCs (1-way analysis of variance). CONCLUSION AND
      SIGNIFICANCE: The cytomorphic data derived from this study show that 4 doses of
      intraperitoneal gentamicin administered to the bullfrog caused a decline in the
      areal density of sensory hair cells of the posterior canal crista ampullaris.
      Also noted was an increase in the density of adjacent SPCs. Although speculative,
      the increase in SPC population could be a harbinger of regeneration of the
      vestibular hair cells as suggested by other investigators in different species.
      The significance of present observations will be helpful to initiate future
      studies related to recovery of SNCs in a similarly damaged frog ampullary organ.
      Through a standardized quantitative approach to the study of SNCs and SPCs of the
      crista organ, the vestibulo-toxicity of newly developed drugs can be assessed.

PMID- 15742261
TI  - Neck masses secondary to heterotopic salivary gland tissue: a 25-year experience.
AB  - OBJECTIVES: The aim of this study is to review salivary tumors arising from
      heterotopic salivary inclusions in the periparotid and cervical lymph nodal
      tissues over a 25-year span. METHODS: A retrospective chart review revealed 24
      patients with asymptomatic neck masses treated between 1976 and 2001, whose
      pathology demonstrated heterotopic salivary tissue or neoplasms arising from
      heterotopic salivary tissue. RESULTS: Nine cases were benign periparotid lymph
      nodes with heterotopic salivary inclusions, 3 of which had multimodal
      involvement. Fifteen cases of heterotopic salivary tumors were identified. The
      benign tumors were predominantly Warthin's tumor (8) with 1 pleomorphic adenoma.
      Malignant tumors included mucoepidermoid (3), acinic cell (2), and adenocarcinoma
      (1). Patients were treated by a superficial parotidectomy, neck dissection, or
      simple excision depending on site and preoperative workup. Adjuvant radiation
      therapy was included for high-grade malignancies. Among the 15 tumor patients,
      follow-up ranged from 1 month to 17 years. Nine patients are alive and disease
      free, 5 are deceased, and 1 was lost to follow-up. CONCLUSIONS: Heterotopic
      salivary tissue in periparotid and upper cervical nodes is a more common
      occurrence than historically recognized. Tumorigenic changes arise from
      heterotopic nodal inclusions, and although infrequent, should be considered in
      the differential diagnosis for isolated neck/periparotid masses and parotid
      Warthin's tumor. Suggested management, after a thorough clinical exam/needle
      aspiration biopsy, includes an imaging survey of the parotid gland and neck
      lymphatics with an appropriate resection to include a simple excision,
      parotidectomy, neck dissection, and/or irradiation as indicated. Isolated low
      grade malignant lesions/benign lesions are adequately managed by excision or
      parotidectomy alone. High-grade malignant lesions require more extended surgery
      with possible irradiation.

PMID- 15742262
TI  - Effects of voice therapy on vocal process granuloma: a phonoscopic approach.
AB  - PURPOSE: This study reviewed the effects of a voice therapy program in patients
      who had failed other treatments for vocal process granuloma related to
      laryngopharyngeal reflux. The program was offered to 16 patients, all of whom
      demonstrated contact of the vocal processes at the site of pathology on voicing.
      During an initial evaluation, each patient was counseled regarding the need for
      voice conservation and improved vocal hygiene. Of the 16 patients, 10 agreed to
      undergo voice therapy and were subsequently enrolled in the treatment program.
      METHODS: The primary therapy objective was to modify each patient's vocal fold
      contact pattern so that a small gap remained between the vocal processes during
      voicing. A "phonoscopic" approach to therapy was used. That is, the clinician and
      the patient were able to observe the larynx endoscopically while also listening
      to the voice. This combined aural and visual approach enabled the clinician to
      guide the patient toward the treatment objective with precision and provided
      patients with immediate feedback regarding their progress. RESULTS: Of the 10
      patients who underwent therapy, 8 were able to achieve the treatment objective,
      and all 8 experienced resolution of pathology or a marked reduction in its
      extent. Six patients who did not undergo treatment, and the 2 who were unable to
      achieve the treatment objective, demonstrated minimal or no improvement, or
      worsening of their pathology, over the same period. CONCLUSIONS: The treatment
      program described may be of value to similar patients with resistant granuloma
      related to extraesophageal reflux.

PMID- 15742263
TI  - Clinical characteristics and treatment outcome for nonvestibular schwannomas of
      the head and neck.
AB  - PURPOSE: Studies involving head and neck schwannomas have focused predominantly
      on involvement of the vestibulocochlear nerve complex (acoustic neuroma) because
      of the associated morbidity related to lesions involving that region. However,
      the majority of head and neck schwannomas are not of vestibular nerve origin and
      may also produce significant morbidity due to involvement of the orbit, skull
      base, and cranial nerves. The purpose of this study is to examine the presenting
      signs and symptoms, location, nerve of origin, and outcome after treatment of
      patients with nonvestibular schwannomas of the head and neck. MATERIALS AND
      METHODS: The medical and pathological records of all patients with nonvestibular
      head and neck schwannomas treated at a single institution between 1979 and 1999
      were retrospectively reviewed. RESULTS: Eighteen (69%) of 26 patients presented
      with symptoms secondary to mass effect or nerve deficit. The parapharyngeal space
      was the most common site of tumor origin occurring in 8 patients (31%). The nerve
      of origin was identified in 16 patients (62%). Twenty-three patients (88%) had
      complete surgical excision, and 3 patients (12%) had subtotal resection.
      Postoperative nerve injury occurred in 16 patients (62%) with resolution in 7
      patients (44%). CONCLUSIONS: Nonvestibular head and neck schwannomas occur most
      commonly in the parapharyngeal space, and presenting signs or symptoms are
      usually related to mass effect or neural deficit. Complete tumor removal is often
      achieved, but subtotal or near-total resection may be indicated for patients with
      extensive skull base, middle ear, or facial nerve involvement. Postoperative
      morbidity is associated with nerve injury from the surgical approach and/or
      resection of the involved nerve.

PMID- 15742264
TI  - Intratympanic dexamethasone injection effects on transient-evoked otoacoustic
      emission.
AB  - PURPOSE: To investigate the effects of intratympanic dexamethasone injection,
      which is done because of tinnitus, on transient evoked otoacoustic emission
      (TEOAE) and so determine whether given dexamethasone cause any damage in the
      inner ear. PATIENTS AND METHODS: Twenty-six patients, aged between 32 and 75,
      with subjective tinnitus, were randomly selected. The selected patients were the
      ones whose improvement had not been achieved through minimum 6 months' medical
      therapy (eg, Ginkgo biloba extract EGb 761, betahistidine, and trimetazidin) and
      who were free of systemic or otolaryngologic disease (hypertension, diabetes
      mellitus, hypo/hypertyroidi, hypercholesterolemia, Meniere disease, and
      otosclerosis). Before and after the injections, audiometry including high
      frequency tinnitus matching and TEOAE tests were done. The injections of 4 mg/mL
      dexamethasone were done 5 times in fixed protocols on days 0, 2, 4, 6, and 8.
      After each injection, the patients were kept supine for 60 minutes with the head
      turned 45 degrees to opposite ear. Paired t test was used to compare the
      beginning and final measurements. RESULTS: Temporary pain and vertigo attacks
      which lasted at most for 15 minutes occurred in some patients only during
      injections. Neither infection nor persistent perforation occurred in any
      patients. After the management, there was no significant difference on patient's
      pure tone averages ( P = .067) and high-frequency averages ( P = .592). When the
      obtained TEOAE results before and after management were compared, the only
      significant increase was detected in the reproducibility values ( P = .042).
      There was no significant difference in other TEOAE parameters which are stimulus
      stability, stimulus intensity, and overall signal-to-noise ratio ( P > .05).
      There is no fixed criteria for rejecting a response solely on the
      reproducibility. However, a high value of the reproducibility (or increase in
      reproducibility) is always meaningful. CONCLUSION: Intratympanic dexamethasone
      used for management in many indications, primarily in Meniere and tinnitus
      patients, was found to increase the reproducibility values of otoacoustic
      emission. Despite the fact that there was not a reasonable increase in the
      responses coming from the outer hair cells, the result was considered positive
      for the study as the responses did not decrease. It is found out that 4 mg/mL
      dexamethasone given intratympanically does not adversely affect the outer hair
      cell function as measured by otoacoustic emission. Within the limits of this
      study, dexamethasone appears to be safe when given intratympanically.

PMID- 15742265
TI  - The relationship between the protective effect of amifostine and decreased
      intercellular adhesion molecule 1 expression.
AB  - PURPOSE: The objective of our study was to characterize the relationship between
      the protective effect of amifostine and decreased intercellular adhesion molecule
      1 (ICAM-1) expression in early-phase, radiation-induced otitis media and to
      illustrate the possible mechanism of early-phase radiation-induced otitis media.
      MATERIALS AND METHODS: A comparison study of middle ear tissue was performed by
      the expression of ICAM-1 and the electron microscope from total 38 guinea pigs.
      Group A, consisting of 2 pigs, was used as control, and these pigs were not
      irradiated. Groups B, C, D, and E, consisting of 9 pigs each, were irradiated.
      Sterile saline was administered intraperitoneally to the pigs in groups B and D
      before irradiation, and amifostine was administered intraperitoneally as an
      aqueous solution 30 minutes before irradiation to the pigs in groups C and E. The
      pigs in groups B and C were killed on the second day after irradiation, and the
      pigs in groups D and E were killed 30 days after irradiation. RESULTS:
      Intercellular adhesion molecule 1 was strongly expressed in the middle ear mucosa
      of the irradiated pigs after a 45-Gy dose of radiation was administered. Enhanced
      ICAM-1 expression was accompanied by pathomorphologic changes in the middle ear
      tissue. Scanning electron microscopy demonstrated the changes. Intercellular
      adhesion molecule 1 expression in the mucosa of the groups killed on the second
      day was stronger than that in the mucosa of the groups killed 30 days after
      irradiation. Amifostine protected the middle ear from radiation injury, and we
      found that the expression of ICAM-1 in the middle ear mucosa was down-regulated.
      However, slight expression of ICAM-1 remained 30 days after irradiation.
      CONCLUSIONS: Irradiation increased the expression of ICAM-1 in the middle ear
      mucosa. Amifostine protected the middle ear from early irradiation injury. There
      was a relationship between oxygen free radicals derived from irradiation and up
      regulation of ICAM-1 expression. Continuous ICAM-1 expression might be related to
      stenosis of the eustachian tube.

PMID- 15742266
TI  - Preventive therapy for postoperative purulent otorrhea after ventilation tube
      insertion.
AB  - OBJECTIVE: Treatment modalities which are intraoperative irrigation of the middle
      ear with isotonic saline, postoperative oral antibiotic treatment, and
      postoperative topical antibiotic use have been compared with each other and with
      control group regarding their efficiency in preventing postoperative purulent
      otorrhea after ventilation tube insertion. Moreover, the costs of the treatment
      modalities were analyzed. STUDY DESIGN: Each group consisted of 70 patients, and
      a total of 280 patients were followed up for purulent otorrhea 2 weeks after the
      surgery. The study was a single-blind randomized clinical trial. RESULTS: Ten
      (14.28%) patients in the oral antibiotic group, 11 (15.71%) patients in the
      isotonic saline irrigation group, 6 (8.57%) patients in the topical antibiotic
      drops group, and 21 (30%) patients in the control group had postoperative
      purulent otorrhea. Statistical analysis determined a significant difference
      between each treatment modalities and control group but did not show any
      significant difference between the treatment groups. When the treatment options
      were compared according to their cost, however, the cost per successfully treated
      patient was significantly lower in the saline irrigation group. CONCLUSION:
      Intraoperative saline irrigation of the middle ear provides an effective, easy,
      and cheap treatment in preventing postoperative purulent otorrhea.

PMID- 15742267
TI  - Electrocochleography in patients with Meniere's disease.
AB  - OBJECTIVE: The objective of this study was to evaluate the role of
      electrocochleography (ECoG) in the diagnosis of Meniere's disease. STUDY DESIGN:
      This study is a retrospective case review. METHODS: Patients undergoing ECoG for
      Meniere's disease between 1995 and 2003 were identified and segregated as having
      definite , probable , or possible Meniere's disease according to the 1995
      American Academy of Otolaryngology-Head and Neck Surgery guidelines for Meniere's
      disease classification. Those determined to have probable and possible Meniere's
      disease were then combined to form a less-than-definite group for statistical
      analysis. Electrocochleography summating potential (SP)/action potential (AP)
      ratios were determined, and ratios greater than 0.4 were considered abnormal. The
      2 groups were then compared to assess for any correlation between ECoG with the
      1995 American Academy of Otolaryngology-Head and Neck Surgery Meniere's disease
      classification. RESULTS: Sixty patients with definite Meniere's disease and 37
      with less-than-definite Meniere's disease were identified. Overall, 59.8% had
      abnormally elevated SP/AP ratios. Of those with definite Meniere's disease, 66.7%
      had abnormally elevated SP/AP ratios, whereas of those with less-than-definite
      Meniere's disease, 52.7% had abnormal ECoGs ( P = .069). CONCLUSIONS: A
      significant difference in ECoG results was not seen between the definite and less
      than-definite Meniere's disease groups. Furthermore, approximately 30% of those
      with definite Meniere's disease would not be classified as having Meniere's
      disease based on ECoG results. Because of its lack of sensitivity, ECoG should
      not play a decisive role in determining the presence or absence of Meniere's
      disease.

PMID- 15742268
TI  - A familial occurrence of lip anomaly.
AB  - Lip pits are among the rarest congenital deformities recorded. Initially reported
      in 1845, its familial occurrence has been reported just once. These developmental
      anomalies occur either as an isolated defect or in association with other
      developmental deformities, including cleft lip, cleft palate, or both. They may
      be located at the commissures of the lips or at the midline of the lower lip. Lip
      pits are often inherited as an autosomal dominant trait with variable penetrance.
      Our report of a family in which all of the 3 children (2 girls and 1 boy) and
      their father were involved is in concert with the latter statement.

PMID- 15742269
TI  - Bilateral cystic parotid masses and a hypopharyngeal mass: a case report and
      review of mucosa-associated lymphoid tissue lymphoma in the head and neck.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B-cell lymphoma
      that was first described in gastric mucosa. Although presentation in the parotid
      gland is not unusual, bilateral cystic masses and associated hypopharyngeal
      involvement are rare. We describe an 83-year-old man with a large painless facial
      swelling; he was otherwise asymptomatic. On examination, bilateral parotid masses
      and a mass in the hypopharynx were found. Biopsy of the hypopharynx was
      consistent with MALT lymphoma. The patient was treated with single-agent
      chemotherapy and had a good initial response. MALT lymphoma occasionally
      originates within the salivary glands and other sites in the head and neck
      region. This disease should be considered in the differential diagnosis of cystic
      or bilateral parotid masses and hypopharyngeal masses.

PMID- 15742270
TI  - A rare case of mucoepidermoid carcinoma of the thyroid.
AB  - OBJECTIVES: The aim of the study was to report a recent case of mucoepidermoid
      carcinoma (MEC) of the thyroid, review the pertinent literature, and highlight
      the importance of multimodal treatment in this potentially aggressive malignancy.
      STUDY DESIGN: The study comprise a case report and a review of literature.
      METHODS: A 42-year-old woman had initially presented to another hospital with a
      painful left neck mass. She subsequently underwent left hemithyroidectomy.
      Surgical pathology was significant for lymphocytic thyroiditis and MEC. One month
      later, she presented to us with a right neck mass. RESULTS: The patient underwent
      completion thyroidectomy and selective neck dissection, including level 6, for
      high-grade MEC. Operative findings included 3 lymph nodes positive for metastasis
      and tumor invasion of the transverse cervical vein. Postoperative chemoradiation
      therapy was administered in 2 cycles separated by 1 month. The patient remains
      disease-free 22 months after the last treatment. CONCLUSION: Mucoepidermoid
      carcinoma is a rare malignancy of the thyroid with less than 35 cases reported to
      date. The origins of this tumor are not completely understood, with debate
      regarding whether it arises from solid cell nests of the ultimobranchial
      apparatus or from follicular epithelium. Although MEC of the thyroid has
      frequently been reported as low grade, the aggressive presentation in our patient
      suggests the appropriateness of multimodal therapy.

PMID- 15742271
TI  - Papillary thyroid cancer with an initial presentation of abdominal and flank
      pain.
AB  - PURPOSE: Well-differentiated thyroid cancer typically presents as a thyroid mass.
      Common sites of metastases upon presentation include cervical lymph nodes, lung,
      and bone. Well-differentiated thyroid cancer with clinically apparent kidney
      metastases is rare, with fewer than 20 cases reported in the literature. In the
      vast majority of these cases, the patients had known thyroid neoplasms at the
      time the renal metastases were identified. We report a case of papillary thyroid
      carcinoma that presented with abdominal pain in a 25-year-old woman with no
      previous history of thyroid disease. STUDY DESIGN: This study is a case report.
      RESULTS: The patient underwent radical nephrectomy for a right renal mass, which
      was diagnosed as papillary thyroid carcinoma follicular variant. During
      subsequent evaluation, metastatic disease was also identified in the patient's
      lungs. The patient was treated with total thyroidectomy and iodine 131.
      CONCLUSIONS: Papillary cancer, which ordinarily behaves in an indolent manner,
      can have unusual presentation, including disseminated metastasis on presentation.
      Renal metastases are extremely rare.

PMID- 15742272
TI  - Skull base Wegener's granulomatosis resulting in multiple cranial neuropathies.

PMID- 15742275
TI  - Drugs, science, the press, and politics: an unwieldy melange toward the public
      good.

PMID- 15742276
TI  - Reconstruction of severe anterior maxillary defects using distraction
      osteogenesis, bone grafts, and implants.
AB  - PURPOSE: The purpose of this article is to describe the method for reconstructing
      patients with severe anterior maxillary defects, using a combination of
      distraction osteogenesis, onlay bone grafts, and implants to support either fixed
      or fixed/removable prostheses. MATERIALS AND METHODS: The surgical technique
      involves placement of an extraosseous distraction device followed by greater than
      10 mm of distraction of the alveolus. A corticocancellous graft is harvested from
      the hip to establish sufficient horizontal bone for implant placement. Implants
      are placed after graft consolidation followed by fabrication of a fixed or
      fixed/removable prosthesis depending on the needs of the individual patient.
      RESULTS: Five patients have been prospectively followed using this technique,
      with completion of their prosthetic reconstruction, with follow-up ranging from 1
      to 4 years. CONCLUSION: The combination of distraction, onlay bone grafting, and
      implant placement has been able to reconstruct patients with severe maxillary
      defects.

PMID- 15742274
TI  - Kidney Early Evaluation Program.

PMID- 15742278
TI  - Effect of different splinting methods and fixation periods on root development of
      autotransplanted immature third molars.
AB  - PURPOSE: The aim of the present study was to assess the influence of suture
      splinting for 1 week or rigid fixation for 4 weeks on final root length, root
      length increment, and mobility of autotransplanted immature third molars.
      PATIENTS AND METHODS: The sample consisted of 63 patients with a total of 65
      transplanted immature third molars. All transplants had reached one-half (n = 29)
      to three-fourths (n = 36) of their expected root length. In 24 of the
      transplants, postoperative fixation was carried out with a rigid acid-etch
      composite and wire splint for 4 weeks (rigid group), and in 41 transplants, with
      a suture splint for 1 week (suture group). The fixation method depended on the
      initial stability of the transplants. All transplants were followed up clinically
      and radiologically for a mean period of 3.9 years. RESULTS: Transplants in the
      rigid group revealed a significantly lower final root length ( P = .002) and root
      length increment ( P = .001) than those in the suture group. The differences were
      found to be more pronounced in transplants at earlier developmental stages. No
      differences were found in transplant mobility. CONCLUSIONS: The results of the
      present study indicate that prolonged rigid fixation of autotransplanted immature
      third molars has a significantly negative influence on final root length and root
      length increment, especially in transplants at earlier developmental stages.

PMID- 15742277
TI  - Characterization of different paresthesias following orthognathic surgery of the
      mandible.
AB  - PURPOSE: Paresthesia is a well known consequence of peripheral nerve injury.
      However, the neural mechanisms of the 2 recognized types, spontaneous and
      elicited, are currently unknown. This study aimed to investigate these 2
      paresthesias and the possible mechanisms accompanying orthognathic surgery.
      PATIENTS AND METHODS: Mechanical-touch thresholds and current perception
      threshold were measured before and 7 days after surgery in 60 chin sites (mental
      nerve area) of 30 patients who underwent orthognathic surgery. Similar testing
      was conducted on healthy volunteers (controls). All sites were classified by the
      presence or absence of each paresthesia: spontaneous paresthesia or no
      spontaneous paresthesia, and elicited paresthesia or no elicited paresthesia.
      Presence or absence analyses were followed-up for 6 weeks after surgery. RESULTS:
      Gender differences and maxillary surgery did not change the incidence of
      paresthesia during postoperative week 1 (chi-square test, P > .05). A
      significantly higher mechanical-touch threshold was observed with spontaneous
      paresthesia compared with no spontaneous paresthesia (Mann-Whitney U-test; P <
      .05), but not between no elicited paresthesia and elicited paresthesia (Mann
      Whitney U-test; P > .05). A significant increase in postsurgery current
      perception thresholds values compared with presurgery values was observed at
      2,000 Hz in spontaneous paresthesia, and at 2,000 and 5 Hz in elicited
      paresthesia (paired t test, P < .05). The incidence of spontaneous paresthesia
      decreased more rapidly than elicited, while the latter tended to increase again
      during the 6-week postsurgical test period. CONCLUSION: The results suggested
      that both spontaneous and elicited paresthesias are associated with damage and
      dysfunction in myelinated primary afferent fibers, but additional neural
      mechanisms are implicated during elicited paresthesia.

PMID- 15742279
TI  - The association between the computed tomography findings, histologic features,
      and outcome of osteosarcoma of the jaw.
AB  - PURPOSE: The study goal was to clarify the association between computed
      tomography (CT) findings, histologic features, and outcome of osteosarcoma of the
      jaw (OSJ). MATERIALS AND METHODS: The CT findings and histologic features of 10
      patients with OSJ were retrospectively analyzed. The patients were
      histopathologically diagnosed to have OSJ. The points analyzed on the CT included
      the patterns of osteogenesis and any signs of bone destruction. The histologic
      types were classified according to the 1993 World Health Organization histologic
      classification of bone tumors. Furthermore, the histologic subtype was classified
      into the following 3 types: osteoblastic, chondroblastic, and fibroblastic. The
      grade of the tumor tissue was classified from I to IV. These were compared with
      the affected jaw site and the outcome of the patients with OSJ. RESULTS: All
      tumors were classified into the conventional central osteosarcoma histologically.
      Eight cases were osteoblastic, and 2 cases were chondroblastic. Grade I or II (4
      of 5 patients are alive without disease) dominated in the maxilla, but in
      contrast, grade III or IV (4 of 5 patients are dead of disease or alive with
      disease) dominated in the mandible. A significant association was seen between
      the osteogenesis found on the CT images and the outcome, between the grade and
      the outcome, and between the outcome and the affected jaw site ( P = .02),
      respectively, in OSJ in this study. However, no significant association was
      observed between the CT findings and the histologic features in OSJ in this
      series. CONCLUSIONS: The osteogenesis on the CT, grade, and affected jaw site
      were considered to be prognostic factors in OSJ in this limited series.

PMID- 15742282
TI  - An association between hemifacial microsomia and facial clefting.
AB  - PURPOSE: Hemifacial microsomia (HFM) is a relatively uncommon malformation, a far
      second to cleft lip/palate (CL/P). Transverse oral cleft ("macrostomia") is known
      to be associated with HFM, but there are also reports of concurrent CL/P. We
      undertook a retrospective study of patients with HFM to document the prevalence
      of facial clefting. The hypothesis is that the coexistence of facial clefts and
      HFM suggests a common pathogenic mechanism. MATERIALS AND METHODS: Records of 198
      HFM patients from the database of the Craniofacial Centre at Boston Children's
      Hospital were reviewed. The age, gender, predominant side of HFM, OMENS
      classification, and presence, size, and type of cleft (CL/P, transverse oral
      cleft, or oro-ocular cleft) were documented. We performed chi 2 , t test, and
      Fishers exact analyses to evaluate the association of facial clefting with HFM.
      RESULTS: There were 100 males and 98 females in the HFM study group, with a mean
      age of 15.3 years (range, 1 to 50 years); 90 were right-sided (45%), 79 were left
      sided (40%), and 29 were bilateral (15%). Twenty patients had a CL/P (10%), and
      of these 15 had unilateral CL/P (UCL/P), equally distributed between right and
      left sides, and 5 had bilateral CL/P (BCL/P). There were 9 males and 11 females
      with combined HFM and CL/P. Cleft of the oral commissure (macrostomia) was
      present in 46 (23.0%) of the HFM patients with a left-to-right-to-bilateral ratio
      of 5:6:1. There was a significant association between the predominant side of HFM
      and the side of CL/P ( P < .001) and macrostomia ( P </= .001). We also showed a
      correlation between the severity of the orbital and mandibular deformities in HFM
      and the coexisting facial cleft. CONCLUSIONS: An association implies concurrence,
      more often than by chance, of 2 or more anomalies and suggests an etiopathologic
      link. The finding of ipsilateral labial clefts in 10% of HFM patients, and the
      differing demographic distribution from common labial clefts, suggests an
      overlapping pathogenesis. Whether the cause is genetic or environmental, we
      hypothesize that there may be a common pathway leading to a disturbance in neural
      crest cell migration in HFM patients who also have a facial cleft.

PMID- 15742280
TI  - Diagnostic evaluation of an ultrathin 15,000 fiberoptic arthroscope: comparison
      of arthroscopic and histologic findings in a sheep model.
AB  - PURPOSE: An ultrathin 15,000 fiberoptic-based arthroscope was evaluated for the
      detection of osteoarthritic intra-articular pathologies in sheep
      temporomandibular joints. MATERIALS AND METHODS: Osteoarthritis was bilaterally
      induced in the temporomandibular joints in sheep. Twenty osteoarthritic
      temporomandibular joints were arthroscopically examined and rated with use of the
      ultrathin arthroscope. The arthroscopic observation was then compared with the
      histologic findings. RESULTS: The arthroscope provided excellent vision of the
      osteoarthritic joints. Correlation between arthroscopic and histologic findings
      was 80%. CONCLUSION: The recently developed ultrathin (15,000) arthroscope was
      found to be a highly reliable and efficient tool to diagnose joint space
      pathologies of the osteoarthritic temporomandibular joint.

PMID- 15742281
TI  - Patients perception of recovery after exposure of impacted teeth: a comparison of
      closed- versus open-eruption techniques.
AB  - PURPOSE: This prospective study compared the patients perception of immediate
      postoperative recovery after surgical exposure of impacted teeth, treated with a
      closed-eruption versus an open-eruption surgical technique. PATIENTS AND METHODS:
      Sixty patients (41 females and 19 males; mean age, 15.4 +/- 2.8 years) were given
      a Health-Related Quality of Life (HRQOL) questionnaire to be completed each
      postoperative day (POD) for 7 days. The questionnaire was designed to assess the
      patients perception of recovery regarding pain, oral function, general activity
      measures, and other parameters. The impact of possible predictor variables, such
      as age, gender, length of surgical procedure, tooth location, height of
      impaction, and the need for bone removal, was assessed. RESULTS: Substantial
      impairment and recovery time of pain and analgesic consumption, oral function
      (ability to eat and enjoy food, swallowing and mouth opening), and food
      accumulation were longer after an open-eruption exposure. No differences were
      recorded concerning general activity. Palatal impaction and the need for bone
      removal resulted in delayed recovery after exposure with an open-eruption
      technique. CONCLUSIONS: The immediate postoperative recovery was longer and more
      substantially impaired after open-eruption versus closed-eruption surgical
      techniques. The present study provides information to patients and clinicians
      assisting them in choosing the most appropriate surgical modality in relation to
      quality of health parameters.

PMID- 15742283
TI  - Analysis of skeletal movements in mandibular distraction osteogenesis.
AB  - PURPOSE: The purpose of this study was to use geometric parameters of movement,
      calculated from 3-dimensional computed tomography (CT) data, to determine the
      curvilinear distractor dimensions required to correct mandibular deformities in a
      series of patients. MATERIALS AND METHODS: Preoperative CT scans from 15 patients
      with symmetric (n = 5) and asymmetric (n = 10) deformities were imported into a
      CT-based software program (Osteoplan; an open-source visualization application
      developed by Gering et al at the Surgical Planning Laboratory [SPL, Brigham and
      Womens Hospital, Boston, MA]). The software was used to reconstruct virtual 3
      dimensional models from these scans. Two experienced surgeons, working with a
      computer scientist, then used Osteoplan to create an ideal treatment plan for
      each patient. In each case, the 3-dimensional curvilinear movement was quantified
      using 4 "parameters of movement" (POMs). These parameters were then used to
      prescribe a distraction device capable of executing the planned skeletal
      correction. Curvilinear distractor dimensions calculated by Osteoplan included
      the radius of curvature of the prescribed device, and the distractor elongation,
      pitch, and handedness. RESULTS: Treatment plans including POMs were developed for
      each patient. The radii of curvature for the prescribed distractors ranged from
      2.3 to 14.1 cm, the distractor elongation dimensions ranged from 0.7 to 3.2 cm,
      and the pitch (horizontal plane) dimensions ranged from 0.005 to 0.8 cm.
      Handedness was either a left (n = 12) or right (n = 8) turning helix. CONCLUSION:
      The results of this study indicate that, using geometric parameters of movement
      calculated from 3-dimensional CT scans, curvilinear devices could be prescribed
      for correction of the range of skeletal deformities in this group of patients.

PMID- 15742284
TI  - Incidence of occlusal dental caries in asymptomatic third molars.
AB  - PURPOSE: We sought to determine the incidence of caries experience on the
      occlusal surface of asymptomatic third molars erupted to the occlusal plane and
      to examine the association between the prevalence of caries experience in third
      molars and other molars. PATIENTS AND METHODS: Clinical data were collected from
      healthy patients (ASA Class I, II) with asymptomatic third molars enrolled at 2
      clinical centers in an institutional review board-approved clinical trial. All
      patients with at least one third molar at the occlusal plane and with data at
      baseline and from the most recent of at least 2 follow-up visits were compared in
      the analysis. At each visit, the presence or absence of caries experience on the
      occlusal surface of third molars and on any surface of the first and second
      molars was recorded during clinical and radiographic examinations. RESULTS:
      Median time between baseline and the most recent follow-up examination was 2.9
      years (interquartile range, 1.6 to 4.0 years). Patients (N = 211) were more often
      female (55%) and white (79%). Median age at baseline was 26.6 years
      (interquartile range, 22.7 to 32.6 years). At baseline, 29% of patients were
      affected by third molar occlusal caries, increasing to 33% at follow-up. Older
      patients at baseline had more caries in a third molar than those younger than 25
      years (43% versus 9%). However, patients who were younger at baseline were more
      likely to develop caries in third molars at follow-up (9% versus 19%). Mandibular
      third molars were affected more often than maxillary third molars: 25% versus 19%
      at baseline and 29% versus 22% at follow-up. At baseline and at follow-up, nearly
      all patients with third molar caries, 98% and 99%, also had caries in
      first/second molars. CONCLUSIONS: The 3-year caries incidence in third molars
      erupted to the occlusal plane was highest among younger patients and mandibular
      teeth. The presence of caries in first/second molars at baseline was highly
      predictive of the development of third molar caries during the ensuing 3 years.

PMID- 15742285
TI  - Preoperative autologous blood donation for oral and maxillofacial surgery: an
      analysis of 913 patients.
AB  - PURPOSE: Autologous transfusions are frequently used with elective surgical
      procedures and are a mandated choice under California law. Because unused units
      cannot be transfused to other patients, it is important to assess utilization and
      minimize waste. METHODS: The transfusion needs of 913 consecutive patients
      scheduled for major oral and maxillofacial surgery at the University of
      California San Francisco were evaluated in 3 categories: oncologic and
      reconstructive surgery (563), orthognathic surgery (260), and temporomandibular
      joint surgery (90). RESULTS: 24.9% of patients chose to undergo preoperative
      autologous blood donation. 24.2%, 20.6%, and 11.4% of oncologic and
      reconstructive surgery, orthognathic surgery, and temporomandibular joint surgery
      patients, respectively, who made an autologous donation preoperatively,
      subsequently received a transfusion postoperatively. CONCLUSION: Transfusion
      needs for most oral surgery procedures are clearly overestimated; the relatively
      low risk of blood loss associated with these procedures today should be taken
      into account when asking patients to participate in preoperative autologous blood
      donation.

PMID- 15742286
TI  - The assessment of blood loss in orthognathic surgery for prognathia.
AB  - PURPOSE: It is difficult to predict the need for blood transfusion during
      orthognathic surgery. The purpose of this study was to evaluate differences
      between patients who underwent different orthognathic procedures, and to assess
      the need for transfusion in orthognathic surgery. SUBJECTS AND METHODS: We
      examined 62 prognathic patients who underwent orthognathic surgery in our
      hospital. The subjects were divided into 4 groups according to procedure. Pre-
      and postoperative values of blood parameters were evaluated statistically.
      RESULTS: A greater amount of blood was lost in the double-jaw surgeries than in
      the single-jaw surgeries. There was a significant difference between sagittal
      split ramus osteotomy (SSRO) combined with Le Fort I osteotomy and intraoral
      vertical ramus osteotomy (IVRO) ( P < .05). However, none of the patients
      required transfusion intraoperatively. In all groups except the IVRO group, there
      were significant differences in red blood cell count, hemoglobin, and hematocrit
      between preoperative values and 1 week postoperative values ( P < .05). Although
      the values of red blood cell, hemoglobin, and hematocrit tended to decrease until
      2 weeks postoperative, no complications occurred. Simple regression analysis
      showed significant positive correlation between duration of operation and blood
      loss ( P < .05). CONCLUSION: The present results indicate that there is little
      risk of marked bleeding in routine procedures, and that IVRO causes minimal
      bleeding. Transfusion was not necessary in IVRO or SSRO with or without Le Fort I
      osteotomy.

PMID- 15742287
TI  - A retrospective analysis of the stability and relapse of soft and hard tissue
      change after bilateral sagittal split osteotomy for mandibular setback of 64
      Taiwanese patients.
AB  - PURPOSE: This study was an analysis of the soft and hard tissue changes of the
      facial profile after bilateral sagittal splitting osteotomy for mandibular
      setback of Taiwanese patients. PATIENTS AND METHODS: We collected pre- and
      postsurgical lateral cephalographs of 64 patients (28 males, 36 females) with
      skeletal Class III malocclusion who received combined orthodontic-surgical
      treatment with bilateral sagittal splitting osteotomy mandibular setback at
      Taipei Veterans General Hospital between 1994 and 2000. Nineteen cephalometric
      parameters of (14 linear, 4 angular, and the BS index) soft and hard tissues were
      measured at 1 week before treatment, and 2 months and 1 year after surgery, and
      analyzed by paired t test. RESULTS: Mean patient age was 20.0 +/- 1.6 years. The
      patients underwent an average of 7 mm mandibular setback at the osseous pogonion
      (Pog). Average setbacks at Pog and soft tissue pogonion (pog) were 5.54 mm and
      4.85 mm, respectively, at 1 year after surgery. The setback ratio of Pog/pog was
      1:0.88. The hard tissue relapse at Pog was 21% at 1 year after surgery.
      Improvement in prognathic profile was demonstrated by significant changes in the
      positions of Pog and pog, ANB angle, the distance from lower lip to esthetic line
      (E-L lip), and the BS index after surgery. However, compared with parameters
      obtained from a normal Taiwanese population, the cephalometric data of Pog, pog,
      and BS index still indicated mild prognathism. CONCLUSION: Although mandibular
      prognathism could be grossly improved by bilateral sagittal splitting osteotomy
      mandibular setback, a significant amount of relapse occurred within 1 year after
      surgery. The extent of the postoperatively preserved features showing mandibular
      prognathism should be a concern for both patients and physicians.

PMID- 15742288
TI  - Platelet-rich plasma enhances human osteoblast-like cell proliferation and
      differentiation.
AB  - PURPOSE: Platelet-rich plasma (PRP) is widely used to promote tissue healing.
      However, there is no concrete evidence for the biological effects of PRP. This
      study evaluated the biological effects of PRP on the proliferation and
      differentiation of 2 human osteoblast-like cell lines. MATERIALS AND METHODS:
      Human osteosarcoma cell lines HOS and SaOS-2 were used in this study. PRP was
      prepared from freshly drawn human venous blood containing a large number of
      platelets. The MTT assay was used to examine the effects of PRP on osteoblast
      viability. To evaluate the growth and differentiation, alkaline phosphatase
      activity was assessed and the expression of procollagen type I, osteopontin, and
      osteoprotegerin mRNA was measured using semiquantitative reverse transcriptase
      polymerase chain reaction. Further, core binding factor alpha 1
      (cbfa1/Runx2/AML3/PebpalphaA), a critical regulator of osteoblast
      differentiation, was also determined. RESULTS: The administration of PRP enhanced
      the viability of HOS and SaOS-2 cells in a dose-dependent manner. Alkaline
      phosphatase activity was suppressed during the cell growth phase, but was
      strongly enhanced when the cells reached confluence. Semiquantitative reverse
      transcription polymerase chain reaction analysis showed that PRP enhanced the
      levels of procollagen type I, osteopontin, osteoprotegerin, and core binding
      factor alpha 1 (cbfa1) mRNA. CONCLUSION: These results suggest that PRP has a
      favorable effect on human osteoblast-like cells, and acts both to enhance bone
      regeneration and as an activator in wound healing.

PMID- 15742289
TI  - Effect of platelet-rich plasma with autogenous bone graft for maxillary sinus
      augmentation in a rabbit model.
AB  - PURPOSE: To evaluate the effect of platelet-rich plasma (PRP) on autogenous bone
      graft remodeling during sinus augmentation in a rabbit model. MATERIALS: Twelve
      New Zealand White rabbits were divided randomly into 3 groups based on their time
      of sacrifice (2, 4, and 8 weeks). All animals underwent a general anesthetic and
      harvesting of an autogenous bone graft from the right iliac crest with subsequent
      bilateral maxillary sinus augmentation. PRP was prepared via standard approved
      technique by acquiring 21 cc of autogenous blood and performing differential
      centrifugation to obtain PRP. One cc of PRP was produced that was mixed with
      bovine topical thrombin and calcium chloride. The left maxillary sinus received
      only autogenous bone, while the right maxillary sinus received a mixture of PRP
      mixed with autogenous bone, thus each animal acted as its own control. Equal
      volumes of bone were inserted in each maxillary sinus. Animals were sacrificed at
      2, 4, and 8 weeks and all specimens were harvested for peripheral quantitative
      computed tomography (pQ-CT), static, and dynamic and histomorphometric analysis.
      RESULTS: Student t tests were performed comparing bone density via pQ-CT
      analysis, histomorphometric parameters of total bone area, and bone apposition
      rate. PRP had no statistically significant effect on bone graft healing in
      maxillary sinus augmentation when compared using standard pQ-CT, static, and
      dynamic histologic criteria. CONCLUSION: This study fails to find a direct
      stimulatory effect of PRP on healing of autogenous bone grafts using pQ-CT,
      static, and dynamic histomorphometric analyses.

PMID- 15742291
TI  - Treatment of pediatric facial fractures: the case for metallic fixation.

PMID- 15742290
TI  - Asymptomatic radiolucent lesion of the posterior mandible.

PMID- 15742292
TI  - Use of resorbable plates and screws in pediatric facial fractures.
AB  - PURPOSE: The use of resorbable plates and screws for fixation of pediatric facial
      fractures is both well tolerated and effective. It enables realignment and stable
      positioning of rapidly healing fracture segments while obviating any future
      issues secondary to long-term metal retention. PATIENTS AND METHODS: Forty-four
      pediatric facial fractures were treated over a 10-year period at our institution
      using differing techniques of polymeric bone fixation. Twenty-nine mandible
      fractures in patients under the age of 10 (age range, 6 months to 8 years) were
      treated. Displaced fractures of the symphysis, parasymphysis, body, and ramus
      underwent open reduction and either 1.5-mm or 2.0-mm plate and screw fixation in
      14 patients. Subcondylar fractures were treated by a short period of
      maxillomandibular fixation (3 weeks) achieved with suture ligation between
      resorbable screws placed at the zygoma and symphysis or a circummandibular suture
      attached to a zygomatic screw. Fifteen patients (age range, 4 to 11 years) with
      isolated frontal, supraorbital, intraorbital, or orbitozygomatic fractures were
      treated by open reduction and internal fixation with 1.5-mm resorbable plates,
      mesh, and screws. RESULTS: No long-term implant-related complications were seen
      in any of the treated patients. CONCLUSIONS: Resorbable polylactic and
      polyglycolic acid plates and screws can be an effective fixation method for
      facial fractures in children in the primary and secondary dentition periods.

PMID- 15742293
TI  - Microbiology and management of infected neck cysts.
AB  - PURPOSE: To review and describe the microbiology, diagnosis, and management of
      infected neck cysts. METHOD: Review the current medical literature and current
      textbooks. RESULTS: Staphylococcus aureus and Streptococcus pyogenes are the
      predominant aerobic isolates, while pigmented Prevotella and Porphyromonas spp.,
      and Peptostreptococcus spp., all part of the oral flora, are the predominant
      anaerobes. Therapy includes administration of antibiotics effective against the
      causative pathogen(s). Proper selection of therapy can be guided by culture of
      the lesion. Surgical drainage and resection may be necessary in case of
      suppuration. Prevention of suppuration can be achieved by surgical removal of
      cysts before acquisition of infection, or removal of those recurrently infected.
      CONCLUSION: Recognition of the importance of the skin or the oral flora in
      infected neck cysts can assist in the proper selection of antimicrobial therapy.

PMID- 15742294
TI  - Management of mandibular fracture using open reduction and internal fixation in a
      neonate: case report.

PMID- 15742295
TI  - Trismus due to bilateral coronoid hyperplasia in a child: case report.

PMID- 15742296
TI  - Alcoholic (beer) sialosis.

PMID- 15742297
TI  - Primary intraosseous carcinoma of the anterior maxilla: report of a new case.

PMID- 15742299
TI  - Pericoronal squamous odontogenic tumor associated with an impacted mandibular
      third molar: a case report.

PMID- 15742298
TI  - Retropharyngeal lymph node metastases from oral cancer: a report of 2 patients.

PMID- 15742300
TI  - Bilateral lingual anesthesia following surgically assisted rapid palatal
      expansion: report of a case.

PMID- 15742302
TI  - Evolutionary artificial neural networks: efficient analysis model or mathematical
      chimera?

PMID- 15742303
TI  - Chlamydia pneumoniae as risk factor of cardiovascular disease in dialysis
      patients.

PMID- 15742304
TI  - Effects of physical exercise in patients with end stage renal failure, on
      dialysis and renal transplantation: current status and recommendations.
AB  - There is increasing evidence about the benefits of regular physical activity in
      the chronically ill. Patients with chronic renal failure prior to and after renal
      transplant are one of the target groups in which increased controlled physical
      activity is highly recommended. Significant atrophy and increased non-contractile
      tissue are present in the muscle of predialytic and patients on hemodialysis,
      which is associated with poor physical performance and poor outcome of renal
      disease. Thus, interventions to increase physical activity or otherwise address
      atrophy may improve performance and quality of life in these patients. Other
      abnormalities in these patients, such as metabolic impairments, anemia, and
      hormonal changes, especially insulin resistance and lipid disorders, could be
      also modulated by certain therapeutic agents and physical activity. Increasing
      activity levels in this target group could be particularly important since it is
      well established that controlled physical exercise reduces the risk of
      cardiovascular disease in the general population. Patients who participate in
      regular physical activity following transplant will have higher health-related
      fitness and quality of life compared to those who remain inactive. The potential
      risk of physical activity can be reduced by medical evaluation, risk
      stratification, careful supervision, and education.

PMID- 15742305
TI  - A technique for the measurement of renal ATP in a large animal model of septic
      shock.
AB  - BACKGROUND: The mechanisms responsible for acute renal failure in sepsis are not
      understood. Measurement of tissue ATP might help to understand this process but,
      in the large animal, it is hampered by major technical difficulties. OBJECTIVE:
      To develop a technique to monitor ATP in the kidney of a large mammal during the
      induction of septic shock and then circulatory arrest. METHODS: Implantation of a
      custom-made phosphorus coil around the left kidney. Induction of septic shock by
      intravenous E. coli administration. Acquisition of 31 P magnetic resonance (MR)
      spectroscopic data at 3-tesla before and during septic shock over several hours.
      Induction of euthanasia and measurement of the same 31 P signal immediately and
      thirty minutes after circulatory arrest. RESULTS: Clear reproducible 31 P MR
      spectra were obtained before and after the induction of septic shock and
      euthanasia. They indicated limited changes in ATP during septic shock. An
      expected rapid and dramatic decrease in ATP occurred with euthanasia.
      CONCLUSIONS: It is possible to sequentially monitor renal bioenergetics in a
      large mammal during septic shock using an implanted custom-made phosphorus coil
      and 3-tesla MR technology. This technique offers a novel approach to the
      investigation of septic renal failure.

PMID- 15742307
TI  - Plasma leakage of oxygenators in ECMO depends on the type of oxygenator and on
      patient variables.
AB  - This study was conducted to identify the causes of plasma leakage of oxygenators
      in extra corporeal membrane oxygenation (ECMO). From 1996 through 2002, 91
      oxygenators were used in 62 patients undergoing ECMO for respiratory and/or
      cardiac failure. Several types of oxygenators were used (Medtronic Maxima,
      Minima, PRF, Medos Hilite). Patient variables and variables related to the ECMO
      set-up were analysed for their relationship with oxygenator failure by a time
      related multiple regression analysis (Cox). Oxygenator failure occurred in 26% of
      the cases. The analysis identified the type of oxygenator (p=0.0016), younger
      patient age (p=0.04) and the number of oxygenators used (p=0.03) as the
      independent significant risk factors. The type of oxygenator used has the most
      overwhelming effect (significantly less leakage with the Medos Hilite). In
      conclusion, leakage of oxygenators is predominantly caused by the type of
      oxygenator used. Patient variables (younger age and the number of oxygenators
      used in one patient) are also significant and allude to an inflammatory process
      as underlying mechanism of plasma leakage.

PMID- 15742306
TI  - Two spent dialysate samples are sufficient for hemodialysis efficacy assessment.
AB  - INTRODUCTION: The measure of dialysis efficacy is expressed as Kt/V value
      (calculated from predialysis and postdialysis blood urea concentration). The aim
      of this study was to assess the possibility of direct calculation of Kt/V value
      from two spent dialysate samples by using the regular blood-based Kt/V
      calculation formula with dialysate samples used as surrogates for blood samples,
      and to detect the most appropriate couple of dialysate samples for Kt/V
      estimation. PATIENTS AND METHODS: Fifty-two single hemodialysis treatments in 34
      anuric patients on chronic bicarbonate low-flux hemodialysis were observed. Kt/V
      values according to Daugirdas formula from two blood samples and from two
      dialysate samples were calculated. RESULTS: Kt/V values calculated according to
      Daugirdas 2 nd generation formula from blood samples (Kt/V sp Daugirdas) were in
      significant correlation with all Kt/V values obtained from two spent dialysate
      samples. The highest correlation coefficient (r = 0.74, p < 0.001) and the least
      standard error of mean of the differences were found between Kt/V sp Daugirdas
      and value obtained with substitution of urea concentration from dialysate samples
      taken 60 minutes after dialysis start and at the end of the dialysis into
      Daugirdas 2 nd generation formula (Kt/V D C D(60) -C D(e) ), which can be
      expressed as a equation of linear regression y = 0.47 + 0.86x. The highest
      correlation coefficient (r =0.74, p < 0.001) was found between Kt/V sp Daugirdas
      values equilibrated according to Daugirdas rate formula, and Kt/V D C D(60) -C
      D(e) value, which can also be expressed as an equation of linear regression y =
      0.43 + 0.73x. CONCLUSION: The results of this study clearly show the sufficiency
      of only two spent dialysate samples for direct estimation of the Kt/V values,
      with no blood sample required.

PMID- 15742308
TI  - Augmentation of abdominal organ perfusion during cardiopulmonary bypass with a
      novel intra-aortic pulsatile catheter pump.
AB  - BACKGROUND: Current pulsatile pumps for cardiopulmonary bypass (CPB) are far from
      satisfactory because of the poor pulsatility. This study was undertaken to
      examine the efficiency of a novel pulsatile catheter pump on pulsatility and its
      effect on abdominal organ perfusion during CPB. METHODS: Twelve pigs weighing
      89+/-11 kg were randomly divided into a pulsatile group (n=6) and a non-pulsatile
      group (n=6). All animals had a CPB for 120 min, aorta clamped for 60 min,
      temperature down to 32 degrees C, and a perfusion flow of 60 ml/kg/min. In the
      pulsatile group, a 21 Fr intra-aortic pulsatile catheter, which was connected to
      a 40 mL membrane pump, was placed in the descending aorta and activated by a
      balloon pump driver during the first 90 minutes of CPB until aortic declamping.
      Hemodynamics, organ blood flow, body metabolism, and blood trauma were studied
      during experiments. RESULTS: Compared with the non-pulsatile group during CPB,
      the pulsatile group had a higher systolic blood pressure (p<0.01), higher mean
      arterial pressure (p<0.05), and higher blood flow to the superior mesenteric
      artery (p<0.05). The hemodynamic energy, indicated by the energy equivalent
      pressure (EEP) was higher in the gastrointestinal tract and kidney in the
      pulsatile group (p<0.01, p<0.01). Abdominal organ perfusion status, as indicated
      by SvO 2 in the inferior vena cava, was higher in the pulsatile group (p<0.05) 30
      min after cessation of CPB. Hemolysis indicated by release of free hemoglobin
      during CPB was similar in the two groups. CONCLUSION: Applying the pulsatile
      catheter pump in the descending aorta is effective in supplying the pulsatile
      flow to the abdominal organs and results in improved abdominal organ perfusion
      during the ischemic phase of CPB.

PMID- 15742309
TI  - Augmentation of butyrate-induced differentiation of human hepatocyte by cyclin E
      over-expression.
AB  - In mammalian cells, cellular differentiation into specific cell types is usually
      preceded by growth arrest. On the other hand, the induced differentiation may
      also be preceded by an enhanced G1-S transition of the cell cycle prior to the
      growth arrest. This suggests that an early increase in proliferation is in some
      way a prerequisite for subsequent differentiation. We therefore attempted to
      assess whether we could produce human hepatocytes with further differentiated
      functions by promoting G1-S transition in a butyrate-treated human hepatocyte
      cell line. A cyclin E-over-expressing cell line was established by transfecting
      human cyclin E cDNA. Upon butyrate treatment, the cyclin E-over-expressing cells
      exhibited a significantly increased albumin-secreting and ammonia-detoxifying
      capacity when compared to the control cells. In particular, the ornithine
      transcarbamylase activity was increased in these cells. Collectively, these
      results implicate that the cyclin E over-expression may augment the hepatocyte
      specific functions during the butyrate-induced differentiation process of human
      hepatocytes by enhancing G1-S cell cycle transition.

PMID- 15742310
TI  - Prosthetic devices shaped as tubular chambers for the treatment of large
      diaphyseal defects by guided bone regeneration.
AB  - Guided tissue regeneration is based on the hypothesis that the different tissues
      have unequal abilities to penetrate a wounded area during the healing process.
      The use of a device acting as a chamber allows the growth of a particular tissue
      and prevents the ingrowth of other tissues which impair the healing process. At
      the same time the chamber protects and maintains in situ the intrinsic growth
      factors so that they may perform their specific activity. Guided tissue
      regeneration currently plays a well-recognized role mostly in dentistry and
      peripheral nerve surgery but interesting perspectives have also opened up in
      orthopedics. Considering the possibility of using guided bone regeneration in the
      repair of diaphyseal bone defects, this updated survey highlights some critical
      points and pathways related to the state-of-the-art of this promising procedure,
      focusing particularly on the properties of the material to make the tubular
      chamber, the use of osteopromotive factors and the most appropriate animal model
      to be used for the experimental evaluation.

PMID- 15742311
TI  - No genotoxicity of a new nickel-free stainless steel.
AB  - Stainless steel is a metallic alloy largely employed in orthopedics,
      maxillofacial surgery and orthodontic therapy. However, the presence in its
      composition of a high quantity of nickel, an agent known to trigger toxic,
      allergic and cancerogenous responses in humans, is cause of some concern. In this
      study, we have investigated the in vitro mutagenicity and genotoxicity of a new
      nickel-free stainless steel, namely P558, in comparison to the conventional
      stainless steel AISI 316L. The cytogenetic effects were evaluated by studying the
      frequency of Sister Chromatid Exchanges (SCE) and chromosomal aberrations. Ames
      test was performed to detect the mutagenic activity. Both P558 and AISI 316L did
      not cause any significant increase in the average number of SCE and in
      chromosomal aberrations, either with or without metabolic activation.
      Furthermore, the Ames test showed that the extracts of both P558 and of AISI 316L
      are not mutagenic. Overall, these findings prove that P558 is devoid of
      genotoxicity and mutagenicity. The present results, together with other previous
      interesting observations that P558 promotes osseointegration, suggest that this
      new nickel-free stainless steel can represent a better alternative to other
      conventional steel alloys.

PMID- 15742312
TI  - The influence of X-ray radiation on the mineral/organic matrix interaction of
      bone tissue: an FT-IR microscopic investigation.
AB  - Fourier transform infrared microscopy was used to investigate human cortical bone
      samples before and after treatment with increasing doses of X-ray radiation.
      Especially the spectral region of the v1 and v3 phosphate vibrations of
      hydroxyapatite, the main mineral component of bone, and the region of the amide I
      and amide II vibrational bands due to the collagen extracellular matrix were
      examined. Major spectral changes in the phosphate region between 1250-1000 cm(-1)
      occur after irradiation doses between 1 and 4 Gray. These findings are explained
      by a decrease in size of mineral crystallites and by variances of the
      toichiometric/non-stoichiometric apatite composition. The Ca2+ /PO4(3-) /HPO4(2-)
      composition in the biological apatite is altered near the bone surface. The
      secondary structure of the collagen matrix is not affected by cumulative
      irradiation up to doses of 15 Gray as indicated by the unchanged frequency
      maximum and contour shape of the amide I band between 1600-1700 cm(-1) . However,
      side chain carboxylate groups of the collagen matrix that are involved in
      coordination with apatite bound calcium ions are partially removed by
      decarboxylation upon irradiation. Concomitantly, a loss of acidic phosphate
      groups due to a formation of phosphate groups with bound calcium is observed.
      These changes on a molecular level can be correlated with alterations in the
      mechanical properties of the bone samples, e.g. with an increased embrittlement
      as deduced from experiments with a scanning acoustic microscope.

PMID- 15742313
TI  - Tissue engineering scheming by artificial intelligence.
AB  - Tissue engineers are often confused when seeking the most effective, economical
      and secure scheme for tissue engineering. The aim of this study is to generate
      tissue engineering schemes with artificial intelligence instead of human
      intelligence. The experimental data of tissue engineered cartilage were
      integrated and standardized with a centralized database, and a scheme engine was
      developed using artificial intelligent methods (artificial neural networks and
      decision trees). The scheme engine was trained with existing cases in the
      database, and then was used to generate tissue engineering schemes for new
      experimental animals. Following the schemes generated by the artificial
      intelligent system, we cured 18 of the 20 experimental animals. In conclusion,
      artificial intelligence is a powerful method for decision making in the tissue
      engineering realm.

PMID- 15742314
TI  - Switching on a signaling pathway with an organoruthenium complex.

PMID- 15742315
TI  - Creation of a tailored aldolase for the parallel synthesis of sialic acid
      mimetics.

PMID- 15742316
TI  - Large-scale identification of proteins expressed in mouse embryonic stem cells.
AB  - A protein subset expressed in the mouse embryonic stem (ES) cell line, E14-1, was
      characterized by mass spectrometry-based protein identification technology and
      data analysis. In total, 1790 proteins including 365 potential nuclear and 260
      membrane proteins were identified from tryptic digests of total cell lysates. The
      subset contained a variety of proteins in terms of physicochemical
      characteristics, subcellular localization, and biological function as defined by
      Gene Ontology annotation groups. In addition to many housekeeping proteins found
      in common with other cell types, the subset contained a group of regulatory
      proteins that may determine unique ES cell functions. We identified 39
      transcription factors including Oct-3/4, Sox-2, and undifferentiated embryonic
      cell transcription factor I, which are characteristic of ES cells, 88 plasma
      membrane proteins including cell surface markers such as CD9 and CD81, 44
      potential proteinaceous ligands for cell surface receptors including growth
      factors, cytokines, and hormones, and 100 cell signaling molecules. The subset
      also contained the products of 60 ES-specific and 41 stemness genes defined
      previously by the DNA microarray analysis of Ramalho-Santos et al. (Ramalho
      Santos et al., Science 2002, 298, 597-600), as well as a number of components
      characteristic of differentiated cell types such as hematopoietic and neural
      cells. We also identified potential post-translational modifications in a number
      of ES cell proteins including five Lys acetylation sites and a single
      phosphorylation site. To our knowledge, this study provides the largest proteomic
      dataset characterized to date for a single mammalian cell species, and serves as
      a basic catalogue of a major proteomic subset that is expressed in mouse ES
      cells.

PMID- 15742317
TI  - Enzymatic incorporation of an antibody-activated blue fluorophore into DNA.

PMID- 15742319
TI  - Profiling serine protease substrate specificity with solution phase fluorogenic
      peptide microarrays.
AB  - A novel microarray-based proteolytic profiling assay enabled the rapid
      determination of protease substrate specificities with minimal sample and enzyme
      usage. A 722-member library of fluorogenic protease substrates of the general
      format Ac-Ala-X-X-(Arg/Lys)-coumarin was synthesized and microarrayed, along with
      fluorescent calibration standards, in glycerol nanodroplets on microscope slides.
      The arrays were then activated by deposition of an aerosolized enzyme solution,
      followed by incubation and fluorometric scanning. The specificities of human
      blood serine proteases (human thrombin, factor Xa, plasmin, and urokinase
      plasminogen activator) were examined. The arrays provided complete maps of
      protease specificity for all of the substrates tested and allowed for detection
      of cooperative interactions between substrate subsites. The arrays were further
      utilized to explore the conservation of thrombin specificity across species by
      comparing the proteolytic fingerprints of human, bovine, and salmon thrombin.
      These enzymes share nearly identical specificity profiles despite approximately
      390 million years of divergent evolution. Fluorogenic substrate microarrays
      provide a rapid way to determine protease substrate specificity information that
      can be used for the design of selective inhibitors and substrates, the study of
      evolutionary divergence, and potentially, for diagnostic applications.

PMID- 15742321
TI  - Boron as a bridging ligand.

PMID- 15742322
TI  - "True" chirality transfer from silicon to carbon: asymmetric amplification in a
      reagent-controlled palladium-catalyzed hydrosilylation.

PMID- 15742320
TI  - Improved proteome coverage by using high efficiency cysteinyl peptide enrichment:
      the human mammary epithelial cell proteome.
AB  - Automated multidimensional capillary liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) has been increasingly applied in various large scale
      proteome profiling efforts. However, comprehensive global proteome analysis
      remains technically challenging due to issues associated with sample complexity
      and dynamic range of protein abundances, which is particularly apparent in
      mammalian biological systems. We report here the application of a high efficiency
      cysteinyl peptide enrichment (CPE) approach to the global proteome analysis of
      human mammary epithelial cells (HMECs) which significantly improved both sequence
      coverage of protein identifications and the overall proteome coverage. The
      cysteinyl peptides were specifically enriched by using a thiol-specific covalent
      resin, fractionated by strong cation exchange chromatography, and subsequently
      analyzed by reversed-phase capillary LC-MS/MS. An HMEC tryptic digest without CPE
      was also fractionated and analyzed under the same conditions for comparison. The
      combined analyses of HMEC tryptic digests with and without CPE resulted in a
      total of 14 416 confidently identified peptides covering 4294 different proteins
      with an estimated 10% gene coverage of the human genome. By using the high
      efficiency CPE, an additional 1096 relatively low abundance proteins were
      identified, resulting in 34.3% increase in proteome coverage; 1390 proteins were
      observed with increased sequence coverage. Comparative protein distribution
      analyses revealed that the CPE method is not biased with regard to protein M(r) ,
      pI, cellular location, or biological functions. These results demonstrate that
      the use of the CPE approach provides improved efficiency in comprehensive
      proteome-wide analyses of highly complex mammalian biological systems.

PMID- 15742325
TI  - Squaring the interface: "surface-assisted" coordination chemistry.

PMID- 15742326
TI  - Real-time spectroscopic and chemical probing of reductive electron transfer in
      DNA.

PMID- 15742327
TI  - Derivatives of the simplest polyhedral carborane anion: structures at the
      borderline between two- and three-dimensional aromatic compounds.

PMID- 15742328
TI  - Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914
      reported cases.
AB  - BACKGROUND: Gastrointestinal (GI) carcinoids, considered to be endocrine
      neoplasms with relatively low levels of malignancy, have never been examined in
      large, statistically reliable series to determine their true aggressive behavior
      in the early stage of both minute (</= 5 mm) or small (5.1-10.0 mm) tumors at a
      depth of invasion restricted to the mucosa and submucosa (sm carcinoids).
      METHODS: Of a total number of 1914 cases of GI sm carcinoids selected from the
      Niigata Registry, 1614 with the tumor size recorded on a millimeter scale were
      categorized in 5-mm size intervals and rates of metastases were calculated for
      those in each size category. Of statistical significance was confirmation that
      the rectum (n = 849), the stomach (n = 449), the duodenum (n = 349), and the
      jejunoileum (n = 149) were among the principal growth sites. The Kaplan-Meier
      method was used to calculate 5-year-survival rates (5YSRs) and a comparative
      study was undertaken. RESULTS: GI sm carcinoids exhibited a metastasis rate of
      16.4% (264 of 1614) as a whole and minute carcinoids (</= 5 mm) revealed an
      unexpectedly high metastasis rate of 6.0% (24 of 399) on average, which ranged
      from 3.7% (8 of 216) in the rectum to 17.2% (5 of 29) in the jejunoileum. Small
      carcinoids measuring 5.1-10 mm also showed a high metastasis rate of 13.3% (90 of
      675) on average, ranging from 9.6% (12 of 125) in the stomach to 41.2% (14 of 34)
      in the jejunoileum. The combined average metastasis rate for both minute and
      small carcinoids combined (</= 10 mm) was as high as 10.6% (114 of 1074). The
      comparative study confirmed that, in both the stomach and the rectum, the
      metastasis rate of sm carcinoids was significantly higher than that for ordinary
      sm carcinomas in tumors > 10 mm. Although most patients (92.8%; 1777 of 1914)
      underwent an endoscopy and/or a wider resection of the lesions, nonresectable
      metastases were found in 22 patients (1.1%). Of these, 16 had undergone a
      laparotomy and 6 had not received surgery. Among 1001 patients with GI sm
      carcinoids, the 5YSRs after curative resection ranged from 98.3% in the rectum to
      89.6% in the stomach (P < 0.05), representing an average of 96.7% for the entire
      series. CONCLUSIONS: Unexpectedly high aggressiveness in metastasis rates in both
      rectal and gastric sm carcinoids > 10 mm exhibiting values significantly higher
      than those of sm carcinomas were found in 1914 patients suffering from GI sm
      carcinoids. However, in sm carcinoids at either the minute or small tumor stage
      (tumors </= 10 mm), the metastasis rates were comparable to those of sm
      carcinomas. It should be emphasized that the 5YSRs for patients with GI sm
      carcinoids may be comparable to those with sm carcinomas in certain cases. These
      points should be taken into consideration when treating patients with GI
      carcinoids, particularly in the early stage, and even with the depth of invasion
      confined to the submucosa.

PMID- 15742329
TI  - Immunocytochemical evaluation of thyroid neoplasms on thin-layer smears from fine
      needle aspiration biopsies.
AB  - BACKGROUND: Fine-needle aspiration biopsy (FNAB) is the most reliable diagnostic
      tool for thyroid nodules. A difficult cytologic diagnosis may be supported by an
      immunocytochemical study. The efficacy of a panel made up of RET, HBME-1, and
      Galectin-3 antibodies was evaluated in smears processed by thin-layer cytology
      (TLC). DESIGN: Thyroid FNABs (n = 99) with both conventional (CS) and thin-layer
      cytology (TLC) smears were studied. The cases were diagnosed as follows: 5 benign
      lesions (BL), 13 papillary carcinomas (PC), and 81 follicular proliferations
      (FP). The category of FP was divided into three subgroups according to nuclear
      features of follicular cells: Follicular neoplasm (FN NOS), oxyphilic follicular
      neoplasm (OFN), and follicular lesion with nuclear pleomorphism (FLWNP).
      Immunostains for HBME-1, Galectin-3, and RET were carried out on TLC slides.
      RESULTS: Among 49 cases undergoing surgery, all 10 PC and 2 BL were
      histologically confirmed, whereas 15 out of 37 FP (40.5%) were malignant. The
      complete immunocytochemical panel (ICCP) was positive in 9 of 10 malignancies
      (90%) and negative in both BLs. Out of 37 FP, the ICCP yielded positive in 15
      cases (4 benign, 11 malignant) and negative in 11 (all benign). In the FLWNP
      subgroup, the ICCP was positive in 11 (84.6%) and negative in 2 histologically
      benign cases. CONCLUSION: The combined panel of antibodies and the nuclear
      pleomorphism of follicular cells were effective in distinguishing between thyroid
      nodules requiring surgery from thyroid nodules requiring just follow-up.

PMID- 15742330
TI  - Prognostic factors in the nonsurgical treatment of esophageal carcinoma with
      radiotherapy or radiochemotherapy: the importance of pretreatment hemoglobin
      levels.
AB  - BACKGROUND: The current study was performed to evaluate prognostic factors for
      overall survival (OS), distant metastasis (DM), and local failure (LF) in
      patients with Stage II/III esophageal carcinoma. METHODS: The following potential
      prognostic factors were retrospectively investigated in 124 patients treated with
      radiotherapy (RT) alone or with radiochemotherapy: age, gender, performance
      status, tumor location, tumor length, histology, histologic grade, T
      classification, N classification, International Union Against Cancer stage,
      chemotherapy, RT dose, and pre-RT hemoglobin level. RESULTS: Using univariate
      analysis (Kaplan-Meier method), pre-RT hemoglobin level, RT dose, tumor length,
      chemotherapy, and performance status were significantly associated with OS.
      Hemoglobin levels of 12.1-14.0 g/dL were associated with the best OS, followed by
      >/= 14.1 g/dL and </= 12.0 g/dL. DM was significantly influenced by tumor length,
      RT dose, N classification, and performance status. LF was significantly
      influenced by pre-RT hemoglobin level, RT dose, and tumor length. Using
      multivariate analysis (Cox proportional hazard model), pre-RT hemoglobin
      maintained significance for OS (P < 0.001) and LF (P < 0.001), RT dose for OS (P
      = 0.001), DM (P = 0.031), and LF (P < 0.001), tumor length for OS (P = 0.003), DM
      (P = 0.017), and LF (P = 0.033), and chemotherapy for OS (P = 0.027). N
      classification was of borderline significance for DM (P = 0.054). Performance
      status lost significance for OS (P = 0.73) and LF (P = 0.22). CONCLUSIONS: The
      strongest predictors for outcome in Stage II/III esophageal carcinoma were RT
      dose, tumor length, pre-RT hemoglobin level, and chemotherapy. The pre-RT
      hemoglobin level was an independent prognostic factor significantly associated
      with OS and LF. A hemoglobin level of 12.1-14 g/dL resulted in a better prognosis
      than hemoglobin levels >/= 14 g/dL and </= 12 g/dL.

PMID- 15742331
TI  - Increasing use of gonadotropin-releasing hormone agonists for the treatment of
      localized prostate carcinoma.
AB  - BACKGROUND: The role of androgen deprivation therapy in prostate carcinoma is
      controversial in earlier stages of disease. The authors examined the time trends
      and patterns of use for androgen deprivation in the form of gonadotropin
      releasing hormone (GnRH) agonists or orchiectomy, in population-based tumor
      registries. METHODS: Data were obtained from the linked Surveillance,
      Epidemiology and End Results-Medicare database. A total of 100,274 men with
      prostate carcinoma diagnosed from 1991 through 1999 were selected. The main
      outcome was the proportion of men who received >/= 1 dose of a GnRH agonist in
      the first 6 months of diagnosis. This was plotted by year and stratified for age,
      grade, stage as well as primary versus adjuvant usage. Multiple logistic
      regression was used to examine predictors of GnRH agonist use in the subset of
      patients with localized cancer. RESULTS: There was a consistent increase in GnRH
      agonist use by year for all ages, stages, and grades. Even in men >/= 80 years
      with localized stage and low to moderate grade tumors, primary GnRH agonist use
      increased over the study period, from 3.7% in 1991 to 30.9% in 1999 (P < 0.001).
      The multivariable analysis showed that significant variability in GnRH agonist
      use existed among SEER geographic regions. CONCLUSIONS: The use of GnRH agonists
      for prostate carcinoma increased dramatically during the 1990s. This increase
      occurred across all stages and histologic grades of prostate carcinoma, and was
      greatest in patients >/= 80 years.

PMID- 15742332
TI  - Conformationally constrained single-chain peptide mimics of relaxin B-chain
      secondary structure.
AB  - Relaxin is a member of the insulin superfamily and has many biological actions
      including angiogenesis and collagen degradation. It is a 6 kDa peptide hormone
      consisting of two peptide chains (A and B) tethered by two disulphide bonds. Past
      structure-function relationship studies have shown the key receptor binding site
      of relaxin to be principally situated within the B-chain alpha-helix. Molecular
      dynamic simulations were performed to aid the design of conformationally
      constrained relaxin B-chain analogues that possess alpha-helical structure and
      relaxin-like activity. Restraints included disulphide bonds, both single and
      double, and lactam bonds. Each peptide was prepared by solid phase synthesis and,
      following purification, subjected to detailed conformational analysis by circular
      dichroism spectroscopy. Of 15 prepared relaxin B-chain mimetics, one was able to
      mimic the secondary structure of the native ligand as indicated by biomolecular
      recognition/interaction analysis using surface enhanced laser desorption
      ionization mass spectroscopy together with a relaxin antibody. However, none of
      the mimetics possess characteristic relaxin-like biological activity which
      strongly indicates that the pharmacophore comprises additional structural
      elements other than the relaxin B-chain alpha-helix. These findings will assist
      in the design and preparation of novel relaxin agonists and antagonists.

PMID- 15742333
TI  - Recent advances in understanding the cell death pathways activated by anticancer
      therapy.
AB  - Over the past two decades, the role of apoptosis in the cytotoxicity of
      anticancer drugs has become clear. Apoptosis may occur via a death receptor
      dependent (extrinsic) or independent (intrinsic or mitochondrial) pathway.
      Mitochondria play a central role in cell death in response to DNA damage, and
      mediate the interaction(s) of various cytoplasmic organelles, including the
      endoplasmic reticulum, Golgi apparatus, and lysosomes. The mitochondrial pathway
      of cell death is mediated by Bcl-2 family proteins, a group of antiapoptotic and
      proapoptotic proteins that regulate the passage of small molecules, such as
      cytochrome c, Smac/Diablo, and apoptosis-inducing factor, which activates caspase
      cascades, through the mitochondrial transition pore. In addition, apoptosis can
      induce autophagic cell death via crosstalk between the two pathways upon
      treatment with anticancer drugs. The current review focused on recent advances
      surrounding the mechanism(s) of cell death induced by anticancer agents and
      discussed potential molecular targets for enhancing the chemotherapeutic
      effect(s) of anticancer agents.

PMID- 15742334
TI  - Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease
      aggressiveness in metastatic ovarian and breast carcinoma.
AB  - BACKGROUND: It was demonstrated previously that the Snail family of transcription
      factors and Smad-interacting protein 1 (Sip1) regulate E-cadherin and matrix
      metalloproteinase 2 (MMP-2) expression, cellular morphology, and invasion in
      carcinoma. For the current study, the authors analyzed the relation between the
      expression of Snail, Slug, and Sip1; the expression of MMP-2 and E-cadherin; and
      clinical parameters in patients with metastatic ovarian and breast carcinoma.
      METHODS: One hundred one fresh-frozen, malignant effusions from patients who were
      diagnosed with gynecologic carcinomas (78 ovarian carcinomas and 23 breast
      carcinomas) were studied for mRNA expression of Snail, Slug, Sip1, MMP-2, and E
      cadherin using reverse transcriptase-polymerase chain reaction analysis. Snail
      mRNA and E-cadherin protein expression levels also were studied in ovarian
      carcinoma effusions using in situ hybridization and immunocytochemistry. The
      results were analyzed for possible correlation with clinicopathologic parameters
      in both tumor types. RESULTS: E-cadherin mRNA expression was lower in breast
      carcinoma (P = 0.001), whereas Snail expression was higher (P = 0.003). The
      Snail/E-cadherin ratio (P < 0.001) and the Sip1/E-cadherin ratio (P = 0.002) were
      higher in breast carcinomas. Sip1 mRNA expression (P < 0.001) and Slug mRNA
      expression (P < 0.001) were correlated with the expression of MMP-2 in ovarian
      carcinomas. The Sip1/E-cadherin ratio was higher in primary ovarian carcinomas at
      the time of diagnosis compared with postchemotherapy ovarian carcinoma effusions
      (P = 0.003), higher in Stage IV tumors compared with Stage III tumors (P =
      0.049), and higher in pleural effusions compared with peritoneal effusions (P =
      0.044). In a univariate survival analysis of patients with ovarian carcinoma, a
      high Sip1/E-cadherin ratio predicted poor overall survival (P = 0.018). High E
      cadherin mRNA expression predicted better disease-free survival (P = 0.023), with
      a similar trend for a low Slug/E-cadherin ratio (P = 0.07). High Snail mRNA
      expression predicted shorter effusion-free survival (P = 0.008), disease-free
      survival (P = 0.03), and overall survival (P = 0.008) in patients with breast
      carcinoma. CONCLUSIONS: Transcription factors that regulate E-cadherin were
      expressed differentially in metastatic ovarian and breast carcinoma. Snail may
      predict a poor outcome in patients who have breast carcinoma metastatic to
      effusions. E-cadherin expression generally was conserved in effusions from
      patients with ovarian carcinoma, but the subset of patients with postulated Sip1
      induced repression of this adhesion molecule had a significantly worse outcome.
      This finding was in agreement with the stronger suppression of E-cadherin by
      Snail and Sip1 in breast carcinoma effusions, a clinical condition associated
      with extremely poor survival.

PMID- 15742335
TI  - A safety catch linker for Fmoc-based assembly of constrained cyclic peptides.
AB  - A new safety-catch linker for Fmoc solid-phase peptide synthesis of cyclic
      peptides is reported. The linear precursors were assembled on a tert-butyl
      protected catechol derivative using optimized conditions for Fmoc-removal. After
      activation of the linker using TFA, neutralization of the N-terminal amine
      induced cyclization with concomitant cleavage from the resin yielding the cyclic
      peptides in DMF solution. Several constrained cyclic peptides were synthesized in
      excellent yields and purities.

PMID- 15742336
TI  - Efficacy of allogeneic hematopoietic stem cell transplantation depends on
      cytogenetic risk for acute myeloid leukemia in first disease remission: a
      metaanalysis.
AB  - BACKGROUND: The efficacy of allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) from a human leukocyte antigen-identical sibling donor remains
      controversial for patients with acute myeloid leukemia (AML) in first complete
      disease remission (CR1). Because the karyotype identified at diagnosis is the
      most relevant prognostic factor for AML, it should be possible to assess the
      efficacy more accurately on the basis of cytogenetic risk. METHODS: The authors
      performed a metaanalysis of five studies, which employed both natural
      randomization based on donor availability and intention-to-treat analysis, with
      overall survival as an outcome of interest. Metaregression analysis was then
      performed to identify the efficacy for patients stratified into the favorable,
      intermediate, and poor cytogenetic risk groups. RESULTS: For the entire cohort,
      there was a statistically significant advantage with allo-HSCT in terms of
      overall survival with a summary hazard ratio of 1.15 (95% confidence interval,
      1.01-1.32, P = 0.037) for the random-effect model. Metaregression analysis showed
      a significant coefficient of +0.24 for the poor cytogenetic risk group, and -0.25
      for the favorable cytogenetic risk group, indicating that the benefit of allo
      HSCT was further increased for the former, and lost for the latter. The
      coefficient for the intermediate cytogenetic risk group was +0.09, and was not
      statistically significant. CONCLUSIONS: These findings suggested that the
      efficacy of allo-HSCT for patients with AML in CR1 depended on cytogenetic risk.
      The beneficial effect of allo-HSCT was yielded for the poor risk group, and
      probably for the intermediate risk groups, but was absent for the favorable risk
      group.

PMID- 15742337
TI  - Carcinoma core distribution in patients with palpable and nonpalpable prostate
      tumors.

PMID- 15742338
TI  - The effects of caffeine and expectancy on attention and memory.
AB  - The present study contrasted caffeine's effects on individuals who expect
      caffeine to stimulate them and those who do not. Secondly, whether a message that
      caffeine rather than placebo was administered would also affect these two groups
      of subjects differently was investigated. The study was conducted single-blind in
      a 2x2x2 mixed design. The between subjects factor was whether they expected
      caffeine to stimulate them (E+) or not (E-) according to their self reports
      obtained before the experiment began. The within subjects factors were message
      (told caffeine vs told placebo) and beverage type (given caffeine vs placebo).
      Sixteen subjects in each group (n=32) performed on signal detection, memory
      scanning and delayed free recall tasks following ingestion of either caffeinated
      or decaffeinated coffee on two sessions each, a total of four experimental
      sessions. On each session, subjects were given a message regarding their drink
      (told caffeine vs told placebo). However, on two sessions there was a mismatch
      between the message and drink given. For signal detection, performance under
      caffeine was better than placebo in the E+ but not the E- group. However,
      subjects in the E+ group did not benefit more than the E- group in either message
      condition. On memory scanning, detections and false alarms did not differ for
      either beverage, nor was there a differential finding in the E+ and E- groups.
      However, reaction time under caffeine condition was shorter. No effects of
      message were found. Caffeine and message also did not have any effect on
      performance on the delayed free recall task. The hypothesis that caffeine and
      message would affect E+ and E- subjects differentially was partly supported.

PMID- 15742339
TI  - New acylated bradykinin analogues: effect on rat blood pressure and rat uterus.
AB  - It was previously reported that acylation of the N-terminus of several known B(2)
      antagonists with various types of bulky acyl groups consistently improved their
      antagonistic potency in the rat blood pressure assay. On the other hand, earlier
      results seem to suggest that the effects of acylation on the contractility of
      isolated rat uterus depend substantially on the chemical character of the acyl
      group, as it was observed that this modification may either change the range of
      antagonism or even transform it into agonism. Bearing all this in mind, three new
      analogues of bradykinin were designed by modifying the moderately potent B(2)
      antagonist, previously synthesized by Stewart's group, D-Arg-Arg-Pro-Hyp-Gly-Thr
      Ser-D-Phe-Thi-Arg. New analogues were obtained by acylation of the N-terminus of
      the above peptide with succinic acid, 12-aminododecanoic acid and 4-aminobenzoic
      acid in order to confirm whether either the positive or the negative charge on
      the N-terminal end of the peptide is responsible for the transformation of
      activity. The activity of analogues was assessed on blood pressure and in
      uterotonic in vitro tests. The modifications proposed either preserved or
      increased the antagonistic potency in the rat blood pressure test. On the other
      hand, the three substituents, depending on their chemical character, differently
      influenced the interaction with the rat uterine receptors. The results may be of
      value in the design of new B(2) agonists and antagonists.

PMID- 15742340
TI  - Antioxidant activity of Ganoderma lucidum in acute ethanol-induced heart
      toxicity.
AB  - The hot water extract of the mushroom Ganoderma lucidum was shown to have
      antioxidative effect against heart toxicity. Investigations into the mechanisms
      of action, level of lipid peroxidation level in vivo, and superoxide scavenging
      activity were also conducted. The mice were divided into six groups with ten
      animals in each group. Ganoderma lucidum, at doses of 10, 25 and 50 mg/kg (p.o.)
      was administered. Superoxide anions were assayed by UV spectrophotometer using
      the cytochrome C reduction method. The results of this study showed that
      Ganoderma lucidum exhibited a dose-dependent antioxidative effect on lipid
      peroxidation and superoxide scavenging activity in mouse heart homogenate.
      Additionally, this result indicated that heart damage induced by ethanol shows a
      higher malonic dialdehyde level compared with heart homogenate treated with
      Ganoderma lucidum. It is concluded that the antioxidative activity may therefore
      contribute to the cardioprotective effect of Ganoderma lucidum, and may therefore
      protect the heart from superoxide induced damage.

PMID- 15742341
TI  - Evaluation of the antioxidant and free radical scavenging properties of Secamone
      afzelii Rhoem.
AB  - The antioxidant activity of a methanol extract of Secamone afzelii stems was
      tested using the DPPH assay and the active compound was identified as alpha
      tocopherol. HPLC determination showed that 0.12% w/w alpha-tocopherol was present
      in the plant. The total extract also showed effective free radical scavenging
      activity in the assay for non-enzymatic lipid peroxidation in liposomes with an
      IC50 value of 90 microg/mL, with alpha-tocopherol isolated from the plant having
      an IC50 of 15 microg/mL in the same system, thus demonstrating the presence of
      other antioxidants.

PMID- 15742342
TI  - Hepatoprotective and antioxidant effects of Alnus japonica extracts on
      acetaminophen-induced hepatotoxicity in rats.
AB  - The stem bark of the Betulaceae plant Alnus japonica, which is indigenous to
      Korea, has been used as a popular folk medicine for hepatitis and cancer. In this
      study, the antioxidant activity of the crude extract and the hepatoprotective
      activities on acetaminophen (AAP)-induced toxicity in the rat liver were
      evaluated. We investigated the effect of the methanol (AJM) and solvent fracton
      of the stem bark of Alnus japonica (AJ) on AAP-induced hepatotoxicity in rats. In
      rat hepatocyte culture, pretreatment with AJM (50, 100, 150 and 200 microg/ml)
      significantly decreased the cytotoxicity of AAP in a dose-dependent manner. The
      pretreated with EtOAc and BuOH fraction led to an increase in free radical
      scavenging activity and a decrease in inhibition of lipid peroxidation, both
      superoxide dismutase and catalase prevent the hepatotoxicity by AAP in the
      treatment of A. japonica fraction. We conclude that AJ is an important
      antioxidant in AAP-induced live hepatotoxicity and that extract of AJM plays a
      hepatoprotective effects in the against AAP-induced cytotoxicity in cultured rat
      hepatocytes in vitro. Pending more evaluation for safety and efficacy, AJ can
      potentially be used in mitigating AAP-induced hepatotoxicity.

PMID- 15742343
TI  - Analgesic, antiinflammatory and antidiabetic properties of Harpagophytum
      procumbens DC (Pedaliaceae) secondary root aqueous extract.
AB  - South Africa is blessed with a rich floral biodiversity of medicinally useful
      plants. One such plant is Harpagophytum procumbens DC (Family: Pedaliaceae). H.
      procumbens is widely used in South African traditional medicine for the
      treatment, management and/or control of a variety of human ailments. In the
      present study, the analgesic effect of H. procumbens secondary root aqueous
      extract was evaluated in mice, using the 'hot-plate' and 'acetic acid' test
      methods; while the antiinflammatory and antidiabetic effects of the plant's
      secondary root extract were investigated in rats. Fresh egg albumin-induced pedal
      oedema and streptozotocin (STZ)-induced diabetes mellitus were used as
      experimental test models of inflammation and diabetes Diclofenac (DIC, 100 mg/kg
      i.p.) was used as a reference analgesic and antiinflammatory agent for
      comparison. Chlorpropamide (250 mg/kg p.o.) was used as a reference hypoglycaemic
      agent for comparison. H. procumbens root aqueous extract (HPE, 50-800 mg/kg i.p.)
      produced significant (p < 0.05-0.001) analgesic effects against thermally and
      chemically induced nociceptive pain stimuli in mice. H. procumbens root extract
      (HPE, 50-800 mg/kg i.p.) also produced dose-related, significant reductions (p <
      0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind
      paw oedema. Furthermore, the plant extract (HPE, 50-800 mg/kg i.p.) produced dose
      dependent, significant reductions (p < 0.05-0.001) in the blood glucose
      concentrations of both fasted normal and fasted diabetic rats. The results of
      this experimental animal study indicate that H. procumbens root aqueous extract
      possesses analgesic, antiinflammatory and hypoglycaemic properties, and lend
      pharmacological support to the suggested folklore uses of Harpagophytum
      procumbens root in the management and/or control of painful, arthritic and other
      inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in
      some communities of South Africa.

PMID- 15742344
TI  - Therapeutic efficacy of pycnogenol in experimental inflammatory bowel diseases.
AB  - Pycnogenol was administered for 10 days by gavage to Sprague-Dawley rats fed an
      elemental diet, then inflammatory bowel disease (IBD) was induced by intrarectal
      administration of ethanol 2,4,6-trinitrobenzene sulfonic acid (TNBS). Twelve
      hours after TNBS treatment, the rats were killed, the colon was assessed by a
      macroscopic damage score and mucosa homogenate was assayed for myeloperoxidase
      (MPO) activity. The supplementation of pycnogenol significantly inhibited the
      macroscopic damage score and MPO activity in a dose-dependent manner. These
      results suggested that pycnogenol ameliorates TNBS-induced inflammation by
      radical scavenging activity, and may have beneficial effects as a supplement in
      enteral nutrition for IBD.

PMID- 15742345
TI  - Phytochemical analysis and in vitro antimicrobial activity of two Satureja
      species essential oils.
AB  - The phytochemical GC[sol ]MS analysis and in vitro antimicrobial activity of the
      essential oils of the aerial parts of Satureja montana L. and Satureja cuneifolia
      Ten., collected in Croatia were performed. The major compound of S. montana oil
      was the phenolic monoterpene carvacrol (45.7%). Other important compounds were
      the monoterpenic hydrocarbons p-cymene (12.6%), gamma-terpinene (8.1%) and the
      oxygen-containing compounds carvacrol methyl ether, borneol, thymol and thymol
      methyl ether. The volatile oil of S. cuneifolia was characterized as beta
      cubebene (8.7%), limonene (8.3%), alpha-pinene (6.9%), spathulenol and beta
      caryophyllene. The antimicrobial effects of S. montana and S. cuneifolia oils
      were found to have a broad spectrum activity against multidrug-resistant
      pathogens by the broth microdilution method. These oils were active against all
      the test strains, with the exception of Pseudomonas aeruginosa. Compared with S.
      cuneifolia, savory oil exhibited greater antimicrobial activity. The maximum
      activity of savory oil was observed against Escherichia coli, methicillin
      resistant Staphylococcus aureus and against the yeast (Candida albicans). The
      essential oil of S. cuneifolia was also found to inhibit the growth of medically
      important pathogens such as S. aureus and E. coli. Fungicidal activity for both
      oils against C. albicans and S. cerevisiae was also observed.

PMID- 15742346
TI  - Antioxidant activities of some common ingredients of traditional chinese
      medicine, Angelica sinensis, Lycium barbarum and Poria cocos.
AB  - The antioxidant activities of three popular ingredients of traditional Chinese
      medicine, namely Angelica sinensis (AS), Lycium barbarum (LB) and Poria cocos
      (PC) were evaluated in this study. The results showed that aqueous extracts of
      these crude drugs exhibited antioxidant activities in a concentration-dependent
      manner. All extracts displayed an inhibitory effect on FeCl2-ascorbic acid
      induced lipid peroxidation in rat liver homogenate in vitro, with the order of
      activity LB > AS > PC. The tested extracts showed a superoxide anion scavenging
      activity ranging from 28.8% to 82.2% and anti-superoxide activity varying from
      38.0% to 84.5%. Among the different extracts, LB extract exhibited the lowest
      IC50 values (0.77-2.55 microg/mL) in all model systems tested in this study. The
      present study concludes that LB extract possessed the strongest inhibition on
      malondialdehyde formation in rat liver homogenate, and superoxide anion
      scavenging and anti-superoxide formation activities. These results also suggest
      that LB extract is a good source of antioxidant agent in the daily dietary
      supplement.

PMID- 15742347
TI  - Protection of urinary bladder function by grape suspension.
AB  - Urinary bladder dysfunction secondary to BPH is a major affliction of aging men.
      A rabbit model of partial outlet obstruction was used to evaluate the ability of
      a standardized grape suspension to protect the bladder against obstructive
      bladder dysfunction.Twenty-four New Zealand White rabbits were separated into
      four groups of six rabbits each. Groups 1 and 3 were pretreated by oral gavage
      for 3 weeks with a standardized grape suspension suspended in water; groups 2 and
      4 were treated with vehicle. Groups 1 and 3 received sham operations after 3
      weeks of treatment; groups 2 and 4 received partial outlet obstruction by
      surgically placing a silk ligature loosely around the urethra. At 3 weeks
      following surgery, in vivo and in vitro bladder functions were evaluated. Based
      on both in vivo and in vitro studies, the grape suspension significantly reduced
      the severity of obstructed bladder dysfunction. This is consistent with the
      hypothesis that ischemia is a major etiological factor in obstructive
      dysfunction, and treatment with antioxidants and membrane stabilization compounds
      such as those in the grape suspension can be effective in the treatment of
      obstructive bladder pathology.

PMID- 15742348
TI  - Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a
      morphological and biochemical study.
AB  - Parsley is used by diabetics in Turkey to reduce blood glucose. The present study
      aims to investigate both the morphological and biochemical effects of parsley on
      liver tissue. Rat hepatocytes were examined by light and electron microscopy.
      Degenerative changes were observed in the hepatocytes of diabetic rats. These
      degenerative changes were significantly reduced or absent in the hepatocytes of
      diabetic rats treated with parsley. Blood glucose levels, alanine transaminase
      and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic
      rats treated with parsley demonstrated significantly lower levels of blood
      glucose, alanine transaminase and alkaline phosphatase. The present study
      suggests that parsley demonstrates a significant hepatoprotective effect in
      diabetic rats.

PMID- 15742349
TI  - Inhibitory effects of compounds from Zingiberaceae species on platelet activating
      factor receptor binding.
AB  - Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and
      Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their
      platelet-activating factor (PAF) antagonistic activities on rabbit platelets
      using 3H-PAF as a ligand. Among them, four compounds showed significant
      inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica
      exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3
      deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were
      45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'
      enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained
      from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated
      that these compounds were relatively strong PAF receptor binding inhibitors.

PMID- 15742350
TI  - Analgesic and anti-inflammatory activity of the ethanolic extract from
      Spiranthera odoratissima A. St. Hillaire (Manaca) roots.
AB  - Acetic acid-induced abdominal writhing, the tail flick test and carrageenan
      induced peritonitis were used to study the analgesic and anti-inflammatory
      activity of the crude ethanolic extract from Spiranthera odoratissima roots.
      Pentobarbital-induced sleeping time was used to study the central depressant
      effect of the extract. The ethanolic extract caused a dose dependent inhibition
      of acetic acid-induced abdominal writhing and leukocyte migration, and produced a
      significant, dose-related increase in the duration of sleep. The results suggest
      that Spiranthera odoratissima roots contain compounds with anti-inflammatory and
      central depressant actions.

PMID- 15742351
TI  - Antifungal effect of various essential oils against Candida albicans.
      Potentiation of antifungal action of amphotericin B by essential oil from Thymus
      vulgaris.
AB  - The antifungal effect of the essential oil from Satureja montana L., Lavandula
      angustifolia Mill., Lavandula hybrida Reverchon, Syzygium aromaticum (L.) Merril
      and Perry, Origanum vulgare L., Rosmarinus officinalis L. and six chemotypes of
      Thymus vulgaris L. on Candida albicans growth were studied. The most efficiency
      was obtained with the essential oil from Thymus vulgaris thymol chemotype (MIC
      80% = 0.016 microL/mL and Kaff = 296 microL/mL). The presence in the culture
      medium of essential oil from Thymus vulgaris thymol chemotype (0.01, 0.1, 0.2,
      0.3 microg/mL) and amphotericin B involved a decrease of the MIC 80% of
      amphotericin B. In contrast, the combination of amphotericin B and low
      concentrations (0.00031-0.0025 microg/mL) of essential oil was antagonistic. The
      strongest decrease (48%) of the MIC 80% was obtained with medium containing 0.2
      microL/mL of essential oil. These results signify that the essential oil of
      Thymus vulgaris thymol chemotype potentiates the antifungal action of
      amphotericin B suggesting a possible utilization of this essential oil in
      addition to antifungal drugs for the treatment of mycoses.

PMID- 15742352
TI  - Interactions between aqueous Hypericum perforatum extracts and drugs: in vitro
      studies.
AB  - Physico-chemical interactions between drugs and plant extracts can result in the
      formation of nanoparticles, microparticles and precipitates. The extraction
      method may have an influence on the components of the plant preparations and the
      interactions between drugs and plant extracts. In this study the particle
      formation in different drug-containing preparations of Hypericum perforatum L.
      was compared. The formation of nanoparticles was investigated by PCS and scanning
      electron microscopy. Precipitates were separated from nanoparticles by
      centrifugation or filtration. The particle formation in drug-containing infusions
      and reconstituted methanolic extracts of Hypericum perforatum L. was different.
      In reconstituted dry extracts 21.5% 17alpha-ethinylestradiol and 36.6%
      levonorgestrel was bound to precipitates, in aqueous Hypericum infusions less
      than 4% of the hormones was bound. In infusions containing desipramine
      nanoparticles were formed while the formation of nanoparticles in desipramine
      containing reconstituted extracts was negligible. Up to 10% of desipramine was
      bound to precipitates in reconstituted extracts, but only 4% was associated with
      the precipitate of infusions. The interactions between extracts of Hypericum
      perforatum L. and drugs depended on the extraction method. Reconstituted
      methanolic extracts showed a more intensive binding with oral contraceptives than
      aqueous infusions.

PMID- 15742353
TI  - Pycnogenol stimulates lipolysis in 3t3-L1 cells via stimulation of beta-receptor
      mediated activity.
AB  - The influence of pycnogenol on the glycerol released into the medium in fully
      differentiated 3T3-L1 cells was studied. After incubation for 2 h, pycnogenol
      stimulated glycerol release in a dose-dependent manner. Pretreatment with the
      beta-receptor antagonist, propranolol, significantly reduced pycnogenol-induced
      lipolysis in a dose-dependent manner. When fully differentiated 3T3-L1 cells were
      incubated with pycnogenol, the cyclic adenosine monophosphate content
      significantly increased. These data suggested that pycnogenol has strong
      lipolytic effects via stimulation of beta-receptor mediated activity.

PMID- 15742354
TI  - Effect of an indigenous herbal compound preparation 'Trikatu' on the lipid
      profiles of atherogenic diet and standard diet fed Rattus norvegicus.
AB  - Combating heart disease is one of the challenging problems of biomedical science
      today. Towards this goal an indigenous preparation 'Trikatu' (a herbal
      combination containing Piper longum (fruit), Piper nigrum (fruit) and Zingiber
      officinale (rhizome) dry powder) was fed to normal and cholesterol fed male
      Rattus norvegicus to ascertain its efficacy as a hypolipidaemic agent. Its
      effects on body weight, blood and tissue (aortic, cardiac and hepatic) lipids-
      total, free and esterified cholesterol, low density lipoprotein(LDL) and high
      density lipoprotein(HDL) cholesterol, triglycerides and phospholipids--and the
      atherogenic index were measured. It was found that 'Trikatu' by virtue of its
      ability to reduce triglycerides and LDL cholesterol and to increase HDL
      cholesterol can reduce the risk of hyperlipidaemia and atherosclerosis. Hence
      'Trikatu' can be used as a potent hypolipidaemic agent and it can reduce the
      atherosclerosis associated with a high fat diet.

PMID- 15742355
TI  - Effect of the rhizomes of Astilbe chinensis on UVB-induced inflammatory response.
AB  - The EtOH extract from the rhizomes of Astilbe chinensis (Saxifragaceae) exhibited
      potent antioxidant activity in preliminary screening. Since oxidative stress is
      known to be involved in the inflammatory response after UVB exposure, the ability
      of an A. chinensis extract to inhibit UVB-induced PGE2 and NO production was
      examined. UVB irradiation (35 mJ/cm2) increased PGE2 and NO production, which
      were significantly decreased by pre-administration of the extract in a dose
      dependent manner. The A. chinensis extract also preserved the cellular
      antioxidant capacity after UVB irradiation, which was determined by the GSH
      content. UVB irradiation enhanced the formation of ROS in the keratinocytes,
      which was determined using DCFH-DA, a redox sensitive dye. The levels of
      intracellular ROS were also significantly reduced by pre-treatment of the extract
      in a dose-dependent manner measured 9 h after UVB irradiation. The results
      suggest that the A. chinensis extract may have a protective effect on the UVB
      injured keratinocytes by inhibiting PGE2 and NO production, possibly through the
      inhibition of intracellular ROS accumulation.

PMID- 15742356
TI  - Nuclear survivin predicts recurrence and poor survival in patients with resected
      nonsmall cell lung carcinoma.
AB  - BACKGROUND: Survivin, which is a member of the inhibitor of apoptosis protein
      gene family, regulates both programmed cell death and mitosis. It has been shown
      that survivin expression and its subcellular localization both have prognostic
      value for patients with malignant disease. In this study, the authors
      investigated whether nuclear or cytoplasmic staining of survivin was a prognostic
      marker for patients with lung carcinoma. METHODS: Paraffin-embedded tissue blocks
      from 144 patients with Stage I and II resected nonsmall cell lung carcinoma
      (NSCLC) were obtained for immunohistochemical staining. Three specimens from each
      patient were prepared and stained with a survivin-specific antibody. Nuclear and
      cytoplasmic staining was graded from 1 to 3 based on intensity. RESULTS: Patients
      who had nuclear staining for survivin had a significantly increased risk of
      disease recurrence (hazard ratio, 2.95; P = 0.0046) and death (hazard ratio,
      2.74; P = 0.0086). CONCLUSIONS: The nuclear presence of survivin may be an
      independent biomarker for disease recurrence and overall survival in patients
      with resected Stage I and II NSCLC.

PMID- 15742357
TI  - Supplementation with gliadin-combined plant superoxide dismutase extract promotes
      antioxidant defences and protects against oxidative stress.
AB  - The potential benefits to health of antioxidant enzymes supplied either through
      dietary intake or supplementation is still a matter of controversy. The
      development of dietary delivery systems using wheat gliadin biopolymers as a
      natural carrier represents a new alternative. Combination of antioxidant enzymes
      with this natural carrier not only delayed their degradation (i.e. the superoxide
      dismutase, SOD) during the gastrointestinal digestive process, but also promoted,
      in vivo, the cellular defences by strengthening the antioxidant status. The
      effects of supplementation for 28 days with a standardized melon SOD extract
      either combined (Glisodin) or not with gliadin, were evaluated on various
      oxidative-stress biomarkers. As already described there was no change either in
      superoxide dismutase, catalase or glutathione peroxidase activities in blood
      circulation or in the liver following non-protected SOD supplementation. However,
      animals supplemented with Glisodin showed a significant elevation in circulated
      antioxidant enzymes activities, correlated with an increased resistance of red
      blood cells to oxidative stress-induced hemolysis. In the presence of Sin-1, a
      chemical donor of peroxynitrites, mitochondria from hepatocytes regularly
      underwent membrane depolarization as the primary biological event of the
      apoptosis cascade. Hepatocytes isolated from animals supplemented with Glisodin
      presented a delayed depolarization response and an enhanced resistance to
      oxidative stress-induced apoptosis. It is concluded that supplementation with
      gliadin-combined standardized melon SOD extract (Glisodin) promoted the cellular
      antioxidant status and protected against oxidative stress-induced cell death.

PMID- 15742358
TI  - Improved estimation of controlled direct effects in the presence of unmeasured
      confounding of intermediate variables.
AB  - Adjusting for a causal intermediate is a common analytic strategy for estimating
      an average causal direct effect (ACDE). The ACDE is the component of the total
      exposure effect that is not relayed through the specified intermediate. Even if
      the total effect is unconfounded, the usual ACDE estimate may be biased when an
      unmeasured variable affects the intermediate and outcome variables. Using linear
      programming optimization to compute non-parametric bounds, we develop new ACDE
      estimators for binary measured variables in this causal structure, and use root
      mean square confounding bias (RMSB) to compare their performance with the usual
      stratified estimator in simulated distributions of target populations comprised
      of the 64 possible potential response types as well as distributions of target
      populations restricted to subsets of 18 or 12 potential response types defined by
      monotonicity or no-interactions assumptions of unit-level causal effects. We also
      consider target population distributions conditioned on fixed outcome risk among
      the unexposed, or fixed true ACDE in one stratum of the intermediate. Results
      show that a midpoint estimator constructed from the optimization bounds has
      consistently lower RMSB than the usual stratified estimator both unconditionally
      and conditioned on any risk in the unexposed. When conditioning on true ACDE,
      this midpoint estimator performs more poorly only when conditioned on an extreme
      true ACDE in one stratum of the intermediate, yet outperforms the stratified
      estimator in the other stratum when interaction is permitted. An alternate 'limit
      modified crude' estimator can never perform less favourably than the stratified
      estimator, and often has lower RMSB.

PMID- 15742359
TI  - Newer antidepressants in pregnancy and rates of major malformations: a meta
      analysis of prospective comparative studies.
AB  - BACKGROUND: A substantial number of women of childbearing age suffer from
      depression. Despite this, relatively little is known about the safety of
      antidepressant use during pregnancy. PURPOSE: We conducted a meta-analysis of
      prospective comparative cohort studies to quantify the relationship between
      maternal exposure to the newer antidepressants and major malformations. METHODS:
      We searched Medline, Embase and Reprotox from 1996 to the present for studies
      comparing outcomes in first trimester exposures to citalopram, escitalopram,
      fluoxetine, fluvoxamine, paroxetine, sertraline, reboxetine, venlafaxine,
      nefazodone, trazodone, mirtazapine and bupropion to those of non-exposed mothers.
      Data were combined using a random effects model; heterogeneity was tested with
      chi2, and publication bias with a funnel plot and the Begg-Mazumdar statistic.
      RESULTS: Twenty-two studies were identified, 15 were rejected (4 reviews, 4
      without comparison groups, 2 third trimester exposures, 2 retrospective database
      studies, 2 case reports and 1 duplicate); 7 studies (n = 1774) met inclusion
      criteria. Effects were not heterogeneous (chi2 = 2.04, p = 0.92); funnel plot and
      test (tau = -0.24, p = 0.45) indicated no publication bias. The summary relative
      risk was 1.01 (95%CI: 0.57-1.80). CONCLUSIONS: As a group, the newer
      antidepressants are not associated with an increased risk of major malformations
      above the baseline of 1-3% in the population.

PMID- 15742360
TI  - Ripple activity in the dentate gyrus of dishinibited hippocampus-entorhinal
      cortex slices.
AB  - Fast oscillations at approximately 200 Hz, termed ripples, occur in the
      hippocampus and cortex of several species, including humans, and are thought to
      play a role in physiological (e.g., sensory information processing or memory
      consolidation) and pathological (e.g., seizures) processes. Blocking gamma
      aminobutyric acid type A (GABA(A)) receptor-mediated inhibition represents one of
      the most often used models of epileptiform discharge. Here we found that bath
      application of the GABA(A) receptor antagonist picrotoxin (50 microM) to mouse
      hippocampus-entorhinal cortex slices induced spontaneous epileptiform activity
      (duration 536.6 +/- 146.1 msec, mean +/- SD; interval of occurrence 14.8 +/- 3.3
      sec, n = 12) with two distinct phases of discharge; the first was characterized,
      in the dentate gyrus only, by high-frequency, field oscillations (ripples) at
      206.3 +/- 23.4 Hz (n = 12), whereas the second component corresponded to
      afterdischarges in the theta range frequency. Ripples, which were also recorded
      in "minislices" only of the dentate gyrus, were unaffected by application of the
      mu-opioid receptor agonist (D-Ala2-N-Me-Phe,Gly-ol)enkephalin (10 microM; n = 6)
      or the N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxy-piperazine-4
      yl)-propyl-l-phosphonate (10 microM; n = 5). In contrast, the non-NMDA
      glutamatergic receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (10
      microM; n = 5) completely blocked all picrotoxin-induced activities. In addition,
      application of the GABA(B) receptor agonist baclofen (0.01-0.5 microM; n = 6)
      dose dependently and reversibly abolished all picrotoxin-induced activities. We
      also found that application of the gap-junction decouplers carbenoxolone (0.2-0.5
      mM; n = 6) or octanol (0.2-0.5 mM; n = 3) blocked the second phase while leaving
      ripples unchanged. These findings demonstrate that the disinhibited dentate gyrus
      can generate ripple activity at approximately 200 Hz that is contributed by
      ionotropic glutamatergic mechanisms and is not dependent on either GABA(A)
      receptor-mediated or gap-junction mechanisms.

PMID- 15742361
TI  - Lipopolysaccharide-induced up-regulation of activated macrophages in the
      degenerating taste system.
AB  - Unilateral chorda tympani (CT) nerve section and maintenance on a sodium
      restricted diet leads to a rapid decrease in neurophysiological taste responses
      to sodium in the contralateral, intact CT nerve. Up-regulation of immune function
      with lipopolysaccharide (LPS; 100 microg i.p.) induces a recovery of normal
      sodium taste responses, suggesting that the sodium-deficient diet is
      immunosuppressive. In fact, there is a bilateral increase in the number of
      lingual, activated macrophages in control-fed rats receiving CT nerve section
      that does not occur in sodium-deficient rats after sectioning. In the current
      study, we hypothesized that the LPS-induced recovery of normal taste function in
      sodium-deficient rats is based on an increase in the activated macrophage
      response to denervation. Rats receiving a unilateral CT nerve section, a sodium
      restricted diet, and/or an injection of LPS (100 microg; i.p.) were overdosed
      with pentobarbital at day 2 postsectioning, and tongues were rapidly dissected
      and frozen. Cryosections were then immunohistochemically stained to determine the
      percentage of ED1 staining for activated macrophages or the number of alphabeta
      or gammadelta T cells. Activated macrophage levels were significantly increased
      in sodium-restricted rats that received LPS following unilateral CT nerve
      section, supporting our hypothesis. These novel findings suggest that LPS
      overcomes the immunosuppression induced by the sodium-restricted diet and also
      indicate that the immune system plays a role in regulating taste function after
      neural injury.

PMID- 15742362
TI  - Mice with the deleted neurofilament of low-molecular-weight (Nefl) gene: 1.
      Effects on regional brain metabolism.
AB  - Neuronal intermediate filaments consist of the NFL subunit linked with NFM and
      NFH, and their alterations have been proposed as a pathogenesic cause in motor
      neuron diseases. Depletion of the Nefl gene in mice mimicks the reduced NFL mRNA
      levels seen in amyotrophic lateral sclerosis and causes perikaryal accumulation
      of neurofilament proteins and axonal hypotrophy in motoneurons. NFL -/- mice were
      evaluated for regional brain metabolism by means of quantitative histochemical
      estimation of cytochrome oxidase (COx) activity. The NFL null mice displayed
      enzymatic activity alterations in numerous hindbrain regions, mainly the
      cerebellum, connected regions of the brainstem (red nucleus, vestibular nuclei,
      and reticular formation), and cranial nerve nuclei. All of the affected regions
      presented elevated COx activity, except for the Purkinje cells of the cerebellum
      and the magnocellular red nucleus, where enzymatic activity was lower. NFL
      disrupted mice displayed functional alterations in brainstem sensorimotor regions
      affected in amyotrophic lateral sclerosis.

PMID- 15742363
TI  - Inhibition of collagen synthesis overrides the age-related failure of
      regeneration of nigrostriatal dopaminergic axons.
AB  - To investigate the mechanism of the age-related failure of regeneration of
      transected axons, nigrostriatal dopaminergic axons were unilaterally transected
      in the lateral hypothalamus in adult mice and in immature mice aged postnatal
      days 7, 14, and 21. Ten days after the transection, tyrosine hydroxylase
      immunoreactive axons had regenerated from caudally to rostrally across the lesion
      site in mice transected at postnatal day 7, whereas they stopped and did not
      extend across the lesion site in mice transected at postnatal day 14 or older.
      Reactive astrocytes bearing chondroitin sulfate proteoglycans were observed
      around the lesion in mice transected at all ages. However, a fibrotic scar
      containing type IV collagen-immunoreactive deposits, which was consistently
      formed at the lesion site in mice transected at postnatal day 14 or older, was
      not formed in mice lesioned at postnatal day 7. When 2,2'-dipyridyl, an inhibitor
      of collagen synthesis, was injected into the lesion site at the time of
      transection in both postnatal day 14 and adult mice, the deposition of type IV
      collagen and the formation of a fibrotic scar were completely prevented, and
      large numbers of tyrosine hydroxylase-immunoreactive axons extended across the
      lesion and reinnervated the striatum. These results imply that the fibrotic scar
      formed in the lesion site is a crucial impediment to the regeneration of
      ascending dopaminergic axons in adult mice and suggest that type IV collagen is
      required for the development of the fibrotic response to adult brain injury.

PMID- 15742364
TI  - Effect of titanium dioxide on the oxidative metabolism of alveolar macrophages:
      an experimental study in rats.
AB  - Metallic implants of titanium are used therapeutically in biomedicine because of
      its excellent biocompatibility. However, no metal or alloy is completely inert.
      We have previously shown that titanium oxide (TiO(2)) is transported in blood by
      phagocytic monocytes and deposited in organs such as liver, spleen, and lung 6
      months after intraperitoneal injection (ip). Furthermore, it is well known that
      exposure to metal traces alters the cellular redox status. Thus, the aim of the
      present study was to determine the presence of titanium in target organs after
      chronic exposure, assess the potential structural alterations, and evaluate the
      oxidative metabolism of alveolar macrophages (AM) in the lung. Rats were ip
      injected with 1.60 g/100 g body wt of TiO(2) in saline solution. Organs (liver,
      spleen, lung) were processed for histological evaluation. Reactive oxygen species
      (ROS) in AM obtained by bronchoalveolar lavage (BAL) were evaluated using the
      nitroblue tetrazolium test and quantitative evaluation by digital image analysis.
      The histological analysis of organs revealed the presence of titanium in the
      parenchyma of these organs with no associated tissue damage. Although in lung
      alveolar macrophages TiO(2) induced a significant rise in ROS generation, it
      failed to cause tissue alteration. This finding may be attributed to an adaptive
      response.

PMID- 15742365
TI  - Mutation analysis of the NSD1 gene in a group of 59 patients with congenital
      overgrowth.
AB  - Sotos syndrome is characterized by pre- and post-natal overgrowth, typical
      craniofacial features, advanced bone age, and developmental delay. Some degree of
      phenotypic overlap exists with other overgrowth syndromes, in particular with
      Weaver syndrome. Sotos syndrome is caused by haploinsufficiency of the NSD1
      (nuclear receptor SET domain containing gene 1) gene. Microdeletions involving
      the gene are the major cause of the syndrome in Japanese patients, whereas
      intragenic mutations are more frequent in non-Japanese patients. NSD1 aberrations
      have also been described in some patients diagnosed as Weaver syndrome. Some
      authors have suggested a certain degree of genotype-phenotype correlation, with a
      milder degree of overgrowth, a more severe mental retardation, and a higher
      frequency of congenital anomalies in microdeleted patients. Data on larger series
      are needed to confirm this suggestion. We report here on microdeletion and
      mutation analysis of NSD1 in 59 patients with congenital overgrowth. Fourteen
      novel mutations, two previously described and one microdeletion were identified.
      All patients with a NSD1 mutation had been clinically classified as "classical
      Sotos," although their phenotype analysis demonstrated that some major criteria,
      such as overgrowth and macrocephaly, could be absent. All patients with confirmed
      mutations shared the typical Sotos facial gestalt. A high frequency of congenital
      heart defects was present in patients with intragenic mutations, supporting the
      relevance of the NSD1 gene in the pathogenesis of this particular defect.

PMID- 15742367
TI  - Addressing the "petty tyranny" of IRBs.

PMID- 15742366
TI  - Unrelated patients with a rearrangement of chromosome 2 causing duplication of
      2p23 and deletion of 2q37.
AB  - We describe two unrelated patients who each have a similar chromosome 2 with
      duplication of 2p23 to pter, and deletion of 2q37 to qter. In one, the
      abnormality was derived from his mother with a pericentric inversion. Both
      individuals have frontal bossing; abnormally formed, low set and posteriorly
      rotated ears; redundant nuchal skin; inversion of the nipple(s); fleshy
      fingertips with prominent pads; a sacral dimple; significant developmental
      delay/mental retardation; and G-tube dependency. Most of these features are
      present in previously described individuals with either duplication of the 2p
      terminus or deletion of the 2q terminus. This report is the first that documents
      postnatal viability of individuals with concurrent duplication of 2p and deletion
      of 2q, and also generation of this imbalance through rearrangement of a
      maternally inherited pericentrically inverted 2. This report should be considered
      in the reproductive counseling of individuals with pericentric inversions of
      chromosome 2.

PMID- 15742368
TI  - Bilateral preaxial polydactyly in a WAGR syndrome patient.
AB  - We report on a 30-month-old baby girl with typical clinical features of WAGR
      syndrome. In addition, the patient showed bilateral preaxial polydactyly of the
      feet. Cytogenetic and fluorescent in situ hybridization (FISH) analyses
      identified a deletion, del(11)(p13p14.1), extending from 6.1 to 21.7 Mb in size.
      Although the simultaneous appearance of WAGR and polydactyly has been already
      described, to our knowledge this is the first case in which the characterization
      at the cytogenetic molecular level of a patient with these phenotypes is
      reported. These observations indicate that preaxial polydactyly may be another
      feature of the WAGR syndrome and suggest the existence of a related gene in the
      WAGR critical region or in its proximity.

PMID- 15742369
TI  - Rippling muscle disease may be caused by "silent" action potentials in the
      tubular system of skeletal muscle fibers.
AB  - Rippling muscle disease (RMD) is a generally benign, myotonic-like myopathy
      associated with rapid rolling contractions and percussion-induced contractions.
      These contractions are electrically silent in electromyographic recordings, which
      is taken as evidence that action potentials are not involved in the phenomena.
      The pathophysiological mechanisms underlying the symptoms have not been
      elucidated. Many cases of RMD are caused by mutations in caveolin-3, and
      aberrations in the tubular system are commonly observed. Here, recent data are
      discussed showing that action potentials can travel over substantial distances
      entirely within the transverse and longitudinal tubular systems of a muscle fiber
      and that stretch can induce such action potentials. Action potentials travelling
      in the tubular system in most circumstances probably cannot excite the sarcolemma
      and hence would not be detected. It is suggested that the distinctive
      contractions in RMD may be due to stretch-induced generation of action potentials
      within the tubular system.

PMID- 15742370
TI  - Elevated fibroblast growth factor-23 in hypophosphatemic linear nevus sebaceous
      syndrome.
AB  - We report on an adolescent who experienced the onset of linear nevus sebaceous
      syndrome (LNSS) prior to 1 year of age. At 7 years of age he was diagnosed to
      have hypophosphatemic rickets. He was suboptimally controlled with phosphate and
      calcitriol treatment and sustained numerous insufficiency fractures ipsilateral
      to the linear sebaceous nevus. Fibroblast growth factor-23 (FGF-23), the
      phosphaturic peptide, was elevated in the plasma. Treamtent with the somatostatin
      agonist, octreotide, and excision of the nevus were followed by normalization of
      FGF-23 and clinical improvement. The patient also had hyperimmunoglobulinemia E,
      which responded to octreotide and surgery. We speculate that in some patients
      with LNSS there may be more than one mediator of hypophosphatemia and that FGF-23
      is the mediator of hyperphosphaturia in this and other hypophosphatemic
      syndromes.

PMID- 15742371
TI  - Mathematical model that predicts isometric muscle forces for individuals with
      spinal cord injuries.
AB  - The ideal functional electrical stimulation (FES) system requires a mathematical
      model to provide feedforward control of the stimulation parameters such that they
      are optimal for different individuals across a range of physiological conditions,
      muscles, and tasks. Recently we tested and validated such a model using able
      bodied subjects. The purpose of this study was to determine whether this model
      applied to persons with spinal cord injuries (SCI). To this end, the isometric
      force responses of the paralyzed quadriceps femoris muscles of 14 adolescents and
      young adults were tested. For each subject, the force responses to two six-pulse
      stimulation trains were used to identify the parameter values of the model and
      then the model was used to predict the force responses to three train patterns
      across a range of frequencies in both a nonfatigued and fatigued condition. The
      intraclass correlation coefficients (ICCs) between the experimental and predicted
      force-time integrals and peak forces were above 0.90 for 12 of the 13 stimulation
      trains tested in the nonfatigued condition and all 13 trains tested in the
      fatigued condition. The success of our model with SCI subjects leads us to
      believe that our model may be useful for designing optimal stimulation parameters
      for standing and ambulation in patients who use FES.

PMID- 15742372
TI  - Phototherapy for enhancing peripheral nerve repair: a review of the literature.
AB  - Posttraumatic nerve repair continues to be a major challenge of restorative
      medicine. Although enormous progress has been made in surgical techniques over
      the past three decades, functional recovery after a severe lesion of a major
      nerve trunk is often incomplete and sometimes unsatisfactory. It is thus
      particularly important to investigate clinical protocols to enhance nerve
      regeneration after surgical nerve repair. The present article reviews literature
      on one possible rehabilitation approach for enhancing nerve recovery, namely
      phototherapy. The number of experimental studies that have reported on the
      promoting action of phototherapy on peripheral nerve regeneration, together with
      the few known side effects related to the use of this type of physical therapy,
      make it possible to suggest that the time for broader clinical trials has come.

PMID- 15742374
TI  - Onset and course of chronic inflammatory demyelinating polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is clinically
      heterogeneous. Our purpose was to determine whether initial progression time,
      clinical features, and distribution of nerve conduction slowing at presentation
      correlate with clinical course and prognosis. We examined how findings at
      presentation related to clinical course during an average follow-up time of 4.0
      (range 1.0-9.0) years in 44 patients with CIDP. We calculated terminal latency
      index (TLI), a measure of differential slowing in distal relative to more
      proximal nerve segments. Patients with acute or subacute onset (progression over
      less than 8 weeks) had a higher remission rate (P = 0.012) than patients with
      chronic onset (progression over more than 8 weeks). Patients with proximal
      weakness had a higher remission rate than patients with the distal phenotype (P <
      0.001). All 5 patients with a relapsing course had subacute onset. They had lower
      TLIs, suggesting a more distal pattern of demyelination, than patients with a
      monophasic or chronic course. In conclusion, subacute onset and presence of
      proximal weakness are good prognostic signs that correlate with a high rate of
      recovery to normal in CIDP. Distal accentuation of conduction slowing at
      presentation correlates with subacute onset and a relapsing course.

PMID- 15742373
TI  - Wear analysis of retrieved ceramic-on-ceramic articulations in total hip
      arthroplasty: Femoral head makes contact with the rim of the socket outside of
      the bearing surface.
AB  - We investigated articular bearing surfaces retrieved from three patients with
      ceramic-on-ceramic total hip arthroplasties using high-quality alumina. The
      duration of implantation was 3.5, 3.0, and 2.5 years, respectively. Dislocation
      of the hip joint after implantation did not occur in any patients. The retrieved
      prostheses were examined by stereomicroscopy and scanning electron microscopy
      (SEM). In the main load-bearing area, no wear marks were seen in any sockets.
      However, in all three cases, stripe scars were observed at the rim of the alumina
      inlay under stereomicroscopy, despite the lack of indentation in the socket and
      the stem, which suggests impingement. Such scars were not observed on the load
      bearing surface. Under SEM, the scars showed excessive wear, including material
      excavation, that has not been observed in conventional hip simulator experiments.
      These findings are similar to those of experiments in which a simulator was
      programmed to distract the femoral head from the socket. The present results
      suggest that the femoral head can separate from the socket without neck-socket
      impingement in vivo.

PMID- 15742375
TI  - From the insoluble dye indirubin towards highly active, soluble CDK2-inhibitors.

PMID- 15742376
TI  - PTK 787/ZK 222584, a tyrosine kinase inhibitor of all known VEGF receptors,
      represses tumor growth with high efficacy.
AB  - The angiogenesis inhibitor PTK 787/ZK 222584 (PTK/ZK) blocks all known VEGF
      receptor (VEGFR) tyrosine kinases, including the lymphangiogenic VEGFR3, in the
      lower nanomolar range. From a panel of 100 kinases only PDGFR, c-kit, and c-fms
      are inhibited beyond those in the nanomolar range. PTK/ZK functions as a
      competitive inhibitor at the ATP-binding site of the receptor kinase as shown
      here in kinetic experiments. The VEGF signal blockade in microvascular
      endothelial cells (MVEC) results in a blockade of MVEC proliferation (IC50=30
      nM), without affecting the proliferation of normal tissue cells and tumor cells.
      The efficacy of PTK/ZK depends on its continuous presence within the endothelial
      target cells. Early removal attenuates its antiproliferative activity in vitro.
      Growth inhibition of endothelial cells is fully reversible as demonstrated by
      "washout" experiments. Without inhibiting tumor cell proliferation directly,
      PTK/ZK results in a significant retardation of tumor growth in a number of
      experimental tumor models of different tissue origin. Combination of PTK/ZK with
      an antiandrogen revealed additive effects on tumor-growth inhibition. Treatment
      efficacy was monitored both by tumor weight and by the determination of serum
      concentrations of the surrogate marker PSA. PTK/ZK is currently being
      investigated in patients with different solid tumor types for its therapeutic
      utility. Preliminary data from phase I/II clinical trials of PTK/ZK as a
      monotherapy suggested a positive safety and tolerability profile, which we
      interpret to be a consequence of the high selectivity of the drug for a limited
      number of kinases. Preliminary response, time to progression, and overall
      survival data were promising.1 Based on these encouraging results, PTK/ZK is
      currently in Phase III clinical trials for metastatic colorectal cancer.

PMID- 15742378
TI  - Immuno-carbon nanotubes and recognition of pathogens.

PMID- 15742379
TI  - The influence of various occlusal materials on stresses transferred to implant
      supported prostheses and supporting bone: a three-dimensional finite-element
      study.
AB  - The aim of this numerical analysis was to evaluate the amount and localization of
      stress that occurs with various materials used in implant-crown design under
      functional forces. Computer-aided design techniques and a finite-element stress
      analysis method were used for evaluation. A 4.1 x 10-mm implant placed in the
      mandibular second premolar area was simulated and analyzed. Simulation and
      analysis were performed with the use of COSMOS/M software and Pro/Engineer 2000i
      on a Dual Pentium III 1-GHz computer. Crown designs were as follows: porcelain
      fused to noble metal crown, porcelain fused to base metal crown, In-Ceram
      porcelain crown, and IPS Empress 2 porcelain crown. A 300-N vertical force was
      applied to the centric relation stop points of the crowns. The results of this
      study indicated that different types of restorative materials play an important
      role in the amount and distribution of the stresses in the superstructure and the
      implant. The highest stress values were observed in the IPS Empress 2 porcelain
      crown design (600 MPa). Porcelain fused to base metal and In-Ceram framework
      designs transferred less stress to abutment. Type of restorative materials used
      in implant crown designs are significant factors in the amount and distribution
      of the stresses on superstructure and implant under functional forces. Porcelain
      fused to base metal (149 MPa) and In-Ceram (173 MPa) crown designs induced higher
      von Mises stress values within the framework than porcelain fused to noble metal
      (108 MPa) and IPS Empress 2 (119 MPa) porcelain crown designs.

PMID- 15742380
TI  - Drug discovery process for kinase inhibitors.

PMID- 15742383
TI  - The target discovery process.
AB  - In order to minimise attrition rates in drug development projects, a target
      discovery process is implemented to select and characterise the most suitable
      candidate kinase targets, before lead identification and lead optimisation are
      embarked upon. The process consists of 1) target selection, 2) target assessment,
      and 3) target validation. This rational approach to target discovery, as a
      prerequisite for lead discovery, ensures that new therapeutic targets fulfil a
      set of general criteria, as well as indication-specific, descriptive and
      functional ones. The approach should ultimately maximise the likelihood of
      achieving target-selective inhibition by small-molecule inhibitors with minimal
      in vivo side effects and a therapeutic effect based on a sound biological
      hypothesis.

PMID- 15742384
TI  - High-throughput screening for kinase inhibitors.
AB  - Following G protein-coupled receptors (GPCRs), protein kinases have become the
      second most important class of targets for drug discovery over the last 20 years.
      While only four kinase inhibitors have reached the market to date (Fasudil for
      rho-dependent kinase, Rapamycin for TOR, Gleevec for BCR-Abl, and Iressa for
      EGFR), many more are already in clinical development. A historical overview of
      kinase inhibitors was recently published by Cohen. [1] After the previous
      successes, protein kinases are now regarded as attractive, well-drugable targets,
      and the analysis of the human genome has yielded 518 protein kinases. [2] We can
      thus expect screening for protein kinase inhibitors to become even more important
      in the future. In this review we will focus on the early steps of drug discovery
      programs producing new lead compounds. We will guide the reader through efficient
      state-of-the-art assay development and high-throughput screening of large
      chemical libraries for protein kinase inhibitors.

PMID- 15742385
TI  - Target-family-oriented focused libraries for kinases--conceptual design aspects
      and commercial availability.

PMID- 15742386
TI  - Peptide arrays for kinase profiling.

PMID- 15742387
TI  - Bioprocess intensification in flow-through monolithic microbioreactors with
      immobilized bacteria.
AB  - Microporous polymers (with porosity up to 90%) with a well-prescribed internal
      microstructure were prepared in monolithic form to construct a flow-through
      microbioreactor in which phenol-degrading bacteria, Pseudomonas syringae, was
      immobilized. Initially, bacteria was forced seeded within the pores and
      subsequently allowed to proliferate followed by acclimatization and phenol
      degradation at various initial substrate concentrations and flow rates. Two types
      of microporous polymer were used as the monolithic support. These polymers differ
      with respect to their pore and interconnect sizes, macroscopic surface area for
      bacterial support, and phase volume. Polymer with a nominal pore size of 100
      microm with phase volume of 90% (with highly open pore structure) yielded reduced
      bacterial proliferation, while the polymer with nominal pore size of 25 microm
      with phase volume of 85% (with small interconnect size and large pore area for
      bacterial adhesion) yielded monolayer bacterial proliferation. Bacteria within
      the 25 microm polymer support remained monolayered, without any apparent
      production of extracellular matrix during the 30-day continuous experimental
      period. The microbioreactor performance was characterized in terms of volumetric
      utilization rate and compared with the published data, including the case where
      the same bacteria was immobilized on the surface of microporous polymer beads and
      used in a packed bed during continuous degradation of phenol. It is shown that at
      similar initial substrate concentration, the volumetric utilization in the
      microreactor is at least 20-fold more efficient than the packed bed, depending on
      the flow rate of the substrate solution. The concentration of the bacteria within
      the pores of the microreactor decreases from 2.25 cells per microm2 on the top
      surface to about 0.4 cells per microm2 within 3 mm reactor depth. If the bacteria
      depleted part of the microreactor is disregarded, the volumetric utilization
      increases by a factor of 30-fold compared with the packed bed. This efficiency
      increase is attributed to the reduction of diffusion path for the substrate and
      nutrients and enhanced availability of the bacteria for bioconversion in the
      absence of biofilm formation as well as the presence of flow over the surface of
      the monolayer bacteria.

PMID- 15742388
TI  - Transcriptome profiles for high-cell-density recombinant and wild-type
      Escherichia coli.
AB  - The transcriptome profiles for wild-type (plasmid-free) and recombinant (plasmid
      bearing) Escherichia coli during well-controlled synchronized high-cell-density
      fed-batch cultures were analyzed by DNA microarrays. It was observed that the
      growth phase significantly affected the transcriptome profiles, and the
      transcriptome profiles were significantly different for the recombinant and wild
      type cultures. The response of the wild-type and recombinant cultures to an
      isopropyl-1-thio-beta-D-galactopyranoside- (IPTG-) addition was examined, where
      IPTG induced recombinant protein production in the plasmid-bearing cultures. The
      IPTG-addition significantly altered the transcriptome response of the wild-type
      cultures entering the stationary phase. The IPTG-induced recombinant protein
      production resulted in a significant down-regulation of many energy synthesis
      genes (atp, nuo, cyo), as well as nearly all transcription- and translation
      related genes (rpo, rpl, rpm, rps, rrf, rrl, rrs). Numerous phage (psp, hfl) and
      transposon-related genes (tra, ins) were significantly regulated in the
      recombinant cultures due to the IPTG-induction. These results indicate that the
      signaling mechanism, associated with the recombinant protein production, may
      induce a metabolic burden in the form of a phage defense mechanism. Taken
      together, these results indicated that recombinant protein production initiated a
      cascade of transcriptome responses that down-regulated the very genes needed to
      sustain productivity.

PMID- 15742389
TI  - Uncertainty analysis of penicillin V production using Monte Carlo simulation.
AB  - Uncertainty and variability affect economic and environmental performance in the
      production of biotechnology and pharmaceutical products. However, commercial
      process simulation software typically provides analysis that assumes
      deterministic rather than stochastic process parameters and thus is not capable
      of dealing with the complexities created by variance that arise in the decision
      making process. Using the production of penicillin V as a case study, this
      article shows how uncertainty can be quantified and evaluated. The first step is
      construction of a process model, as well as analysis of its cost structure and
      environmental impact. The second step is identification of uncertain variables
      and determination of their probability distributions based on available process
      and literature data. Finally, Monte Carlo simulations are run to see how these
      uncertainties propagate through the model and affect key economic and
      environmental outcomes. Thus, the overall variation of these objective functions
      are quantified, the technical, supply chain, and market parameters that
      contribute most to the existing variance are identified and the differences
      between economic and ecological evaluation are analyzed. In our case study
      analysis, we show that final penicillin and biomass concentrations in the
      fermenter have the highest contribution to variance for both unit production cost
      and environmental impact. The penicillin selling price dominates return on
      investment variance as well as the variance for other revenue-dependent
      parameters.

PMID- 15742390
TI  - Direct hepatic fate specification from mouse embryonic stem cells.
AB  - The molecules responsible for hepatic differentiation from embryonic stem (ES)
      cells have yet to be elucidated. Here we have identified growth factors that
      allow direct hepatic fate-specification from ES cells by using simple adherent
      monolayer culture conditions. ES cell-derived hepatocytes showed liver-specific
      characteristics, including several metabolic activities, suggesting that ES cells
      can differentiate into functional hepatocytes without the requirement for
      embryoid body (EB) formation, in vivo transplantation, or a coculture system.
      Most importantly, transplantation of ES cell-derived hepatocytes in mice with
      cirrhosis showed significant therapeutic effects. In conclusion, this novel
      system for hepatic fate specification will help elucidate the precise molecular
      mechanisms of hepatic differentiation in vitro and could represent an attractive
      approach for developing stem cell therapies for treatment of hepatic disease in
      humans. Supplementary material for this article can be found on the HEPATOLOGY
      website ( http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

PMID- 15742392
TI  - Effect of Weikangning on gastric cancer cell growth and expression of vascular
      endothelial growth factor and its receptors KDR and Flt-1.
AB  - AIM: To observe the effect of Chinese traditional herbal decoction Weikang-ning
      (WKN) on cell growth and expression of VEGF and its receptors KDR and Flt-1 in
      gastric cancer cell line MGC-803. METHODS: A total of 120 male Wistar rats were
      divided into control group, high dose, medium dose and low dose groups fed with
      natural saline, 20, 10, and 5 g/kg of WKN, respectively. The experimental animals
      were finally killed for the preparation of drug-containing serum. The gastric
      cancer cell MGC-803 was cultured with the drug-containing serum drawn from the
      rats in different groups. We observed the growth condition of the cancer cells
      with light microscope and flow cytometer. The expression of mRNA of VEGF and its
      receptors KDR and Flt-1 was detected with RT-PCR. RESULTS: The proportion of
      cells in G(0)-G(1) phase was (65.40+/-0.41)%, (56.92+/-0.62)%, (55.89+/-0.69)% in
      high, medium and low dose groups respectively vs (41.35+/-0.55)% in control group
      (P<0.01), while the cells in G(2)-S and S phases were (11.62+/-0.62)% and
      (22.99+/-0.69)%, (17.08+/-0.80)% and (26.00+/-0.71)%, (19.37+/-0.57)% and
      (24.74+/-0.64)% in high, medium and low dose groups, respectively, vs (23.65+/
      0.56)% and (35.00+/-0.60)% in control group (P<0.01). The expression of mRNA of
      VEGF and its receptors was significantly decreased, the area of electrophoresis
      bands (AREA), the absorptivity of mean optical density (A) and the product of
      AREA and A were significantly lower in WKN-administered groups than that in
      control group (P<0.01). CONCLUSION: The decoction of WKN suppresses the growth of
      gastric cancer cell MGC-803 and decreases the expression of mRNA of both VEGF and
      its receptors KDR and Flt-1.

PMID- 15742391
TI  - Regulation of apoptosis by the papillomavirus E6 oncogene.
AB  - Infection with human papillomaviruses is strongly associated with the development
      of multiple cancers including esophageal squamous cell carcinoma. The HPV E6 gene
      is essential for the oncogenic potential of HPV. The regulation of apoptosis by
      oncogene has been related to carcinogenesis closely; therefore, the modulation of
      E6 on cellular apoptosis has become a hot research topic recently. Inactivation
      of the pro-apoptotic tumor suppressor p53 by E6 is an important mechanism by
      which E6 promotes cell growth; it is expected that inactivation of p53 by E6
      should lead to a reduction in cellular apoptosis, numerous studies showed that E6
      could in fact sensitize cells to apoptosis. The molecular basis for apoptosis
      modulation by E6 is poorly understood. In this article, we will present an
      overview of observations and current understanding of molecular basis for E6
      induced apoptosis.

PMID- 15742393
TI  - Molecular mechanisms of apoptosis induced by Scorpio water extract in human
      hepatoma HepG2 cells.
AB  - AIM: To clarify the mechanism underlying the anti-mutagenic and anti-cancer
      activities of Scorpio water extract (SWE). METHODS: Human hepatoma HepG2 cells
      were incubated with various concentrations of SWE. After 24-h incubation,
      cytotoxicity and apoptosis evaluations were determined by MTT and DNA
      fragmentation assay, respectively. After treatment with SWE, mitochondrial
      membrane potential (MMP) was determined by measuring the retention of the dye
      3,3'-dihexyloxacarbocyanine (DiOC(6)(3)) and the protein expression including
      cytochrome C and poly-(ADP-ribose) polymerase (PARP) were measured by Western
      blotting. Caspase-3 and -9 enzyme activities were measured using specific
      fluorescence dyes such as Ac-DEVD-AFC and Ac-LEHD-AFC. RESULTS: We found that
      treatment with SWE induced apoptosis as confirmed by discontinuous DNA
      fragmentation in cultured human hepatoma HepG2 cells. Our investigation also
      showed that SWE-induced apoptosis of HepG2 cells were associated with
      intracellular events including disruption of MMP, increased translocation of
      cytochrome C from mitochondria to cytosol, activation of caspase-3, and PARP. Pre
      treatment of N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), a caspase-3 specific
      inhibitor, or cyclosporin A (CsA), an inhibitor of MMP disruption, completely
      abolished SWE-induced DNA fragmentation. CONCLUSION: These results suggest that
      SWE possibly causes mitochondrial damage, leading to cytochrome C release into
      cytosol and activation of caspases resulting in PARP cleavage and execution of
      apoptotic cell death in HepG2 cells. These results further suggest that Scorpio
      may be a valuable agent of therapeutic intervention of human hepatomas.

PMID- 15742394
TI  - Decreased expression of type II tumor suppressor gene RARRES3 in tissues of
      hepatocellular carcinoma and cholangiocarcinoma.
AB  - AIM: To analyze the expression of retinoic acid receptor responder 3 (RARRES3)
      protein in paraffin-embedded tissues of hepatocellular carcinoma (HCC) and
      cholangiocarcinoma (CC), and the correlation of RARRES3 production with tumor
      differentiation. METHODS: Expression of RARRES3 in tissues from 21 CC (10 well-,
      7 moderately- and 4 poorly-differentiated) and 32 HCC was determined by
      immunohistochemistry. RESULTS: Among 21 CC tissues, RARRES3 was detected in 8
      (80%) of 10 well-differentiated tumors. Only 2 (18.2%) out of 11 tumors with
      moderate or poor differentiation showed positive RARRES3 expression. RARRES3
      expression in well-differentiated CC was significantly higher than that in tumors
      with moderate or poor differentiation (Fisher exact test, P<0.01). Expression of
      RARRES3 was not different between early (I and II) and late (III and IV) stages
      of CC. Among 30 HCC tissues, 17 (56.7%) weakly expressed RARRES3 in HCC cells,
      and 25 (83.3%) normal tissues adjacent to HCC expressed the protein. RARRES3
      expression was significantly decreased in HCC tissues compared to that in
      adjacent normal tissues (logistic regression analysis, OR = 0.27, 95% CI (0.11
      0.62), P<0.01). CONCLUSION: Expression of RARRES3 is positively correlated to
      well-differentiated CC, which supports the role of RARRES3 in malignant
      epithelial differentiation of the tumor. The decrease in RARRES3 expression in
      tissues of HCC and CC with moderate and poor differentiation suggests that
      altered RARRES3 expression may play a role in the carcinogenesis of the liver and
      biliary tract.

PMID- 15742395
TI  - High-density lipoprotein as a potential carrier for delivery of a lipophilic
      antitumoral drug into hepatoma cells.
AB  - AIM: To investigate the possibility of recombinant high-density lipoprotein
      (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.
      METHODS: Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by
      cosonication of apoproteins from HDL (Apo HDL) and ACM as well as
      phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by
      electrophoretic mobility, including the size of particles, morphology and
      entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was
      determined by competition assay in the presence of excess native HDL. The
      cytotoxicity of rHDL-ACM was assessed by MTT method. RESULTS: The density range
      of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity
      of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL
      ACM were more than 90%. rHDL-ACM particles were typical sphere model of
      lipoproteins and heterogeneous in particle size. The average diameter was 31.26+/
      5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of
      lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be
      competed against in the presence of excess native HDL. rHDL-ACM had same binding
      capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma
      cells was significantly higher than that of free ACM at the concentration range
      of 0.5-10 microg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was
      significantly higher than that of free ACM at concentration range of less than 5
      microg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68
      nmol/L vs 3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the
      cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01)
      and in a dose-dependent manner at the concentration range of 0.5-10 microg/mL.
      Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than
      that to L02 cells at concentration range of 1-7.5 microg/mL (P<0.01). IC50 for
      SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L),
      showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells. CONCLUSION:
      rHDL-ACM complex keeps the basic physical and biological binding properties of
      native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal
      L02 hepatocytes. HDL is a potential carrier for delivering lipophilic antitumoral
      drug to hepatoma cells.

PMID- 15742396
TI  - Immunohistochemical assessment of angiogenesis in hepatocellular carcinoma and
      surrounding cirrhotic liver tissues.
AB  - AIM: To investigate whether vascular endothelial growth factor (VEGF) was over
      expressed in hepatocellular carcinoma (HCC) or in surrounding cirrhotic liver
      tissues. METHODS: Immunohistochemistry was performed to investigate the
      expression of VEGF proteins in HCC tissues from 105 consecutive patients
      undergoing curative resection for HCC. The immunostaining results and related
      clinicopathologic materials were analyzed with statistical methods. Kaplan-Meier
      method was used to calculate survival curves, and Log-rank test was performed to
      compare differences in survival rates of the patients with positive HCC staining
      and negative VEGF. RESULTS: VEGF-positive expression was found in 72 of 105 HCC
      patients (68.6%). Capsular infiltration (P = 0.005), vascular invasion (P =
      0.035) and intrahepatic metastasis (P = 0.008) were observed more frequently in
      patients with VEGF-positive expression than in those with VEGF-negative
      expression. Kaplan-Meier curves showed that VEGF-positive expression was
      associated with a shorter overall survival (P = 0.014). VEGF-positive expression
      was found in 47 of tissues 68 HCC (69.1%), and VEGF-positive expression was found
      in 54 of 68 surrounding cirrhotic liver tissues (79.4%). VEGF-positive expression
      was significantly higher in surrounding cirrhotic liver tissues than in HCC (P =
      0.017). CONCLUSION: VEGF may play an important role in the angiogenesis and
      prognosis of HCC, as well as in the angiogenesis of liver cirrhosis.

PMID- 15742397
TI  - Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2
      and 4 in colorectal adenocarcinoma: Immunohistochemical analysis and correlation
      with clinicopathological factors.
AB  - AIM: There is strong evidence that tyrosine kinases are involved in the
      regulation of tumor progression, cellular growth and differentiation. Recently,
      many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and
      Tie-2 receptors constitute a major class. Angiopoietin (Ang)-1 is known as a
      ligand of Tie-2 tyrosine kinase receptor. The objective of this study was to
      establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4 expression profile
      in human colorectal adenocarcinomas. METHODS: We examined 96 cases of surgically
      resected human colorectal adenocarcinoma by immunohistochemistry and investigated
      the statistical correlation between the expressions of Ties and Angs and
      clinicopathological factors. RESULTS: Among the 96 cases of adenocarcinoma, 87
      (90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76 cases (79.2%) showed positive
      staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2
      and 4 proteins, respectively. Histologically, the expressions of Ties and Angs
      were variable. The expressions of Ties and Angs were correlated with several
      clinicopathological factors, but did not correlate with the presence of lymph
      node metastasis. Ties and Angs were highly expressed in human colorectal
      adenocarcinoma cells. CONCLUSION: These findings suggest that the Tie-Ang
      receptor-ligand complex is one of the factors involved in the cellular
      differentiation and progression of human colorectal adenocarcinoma.

PMID- 15742398
TI  - Hepatitis G virus genomic RNA is pathogenic to Macaca mulatta.
AB  - AIM: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by
      observing replication and expression of the virus, as well as the serological and
      histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA
      positive serum. METHODS: Full-length HGV cDNA clone (HGVqz) was constructed and
      proved to be infectious, from which HGV genomic RNA was transcribed in vitro.
      Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA
      positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and
      then BB1 was infected with serum from BM1. Serum and liver tissue were taken
      regularly, and checked with RT-PCR, in situ hybridization and other
      immunological, serological, histological assays. RESULTS: Serum HGV RNA was
      detectable in all the 3 Macaca mulattas, serological and histological
      examinations showed the experimental animals had slightly elevated alanine
      transaminase (ALT) and developed HGV viremia during the infectious period. The
      histology, immunohis-tochemistry, and in situ hybridization in liver tissues of
      the inoculated animals demonstrated a very mild hepatitis with HGV antigen
      expression in cytoplasm of hepatocytes. RT-PCR and quantitative PCR results
      showed that HGV could replicate in liver. CONCLUSION: The genomic RNA from full
      length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis.
      HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to
      other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and
      therefore can be used as an experimental animal model for the studies of HGV
      infection and pathogenesis.

PMID- 15742399
TI  - Comparison of Helicobacter pylori infection and gastric mucosal histological
      features of gastric ulcer patients with chronic gastritis patients.
AB  - AIM: To compare Helicobacter pylori infection and gastric mucosal histological
      features of gastric ulcer patients with chronic gastritis patients in different
      age groups and from different biopsy sites. METHODS: The biopsy specimens were
      taken from the antrum, corpus and upper angulus of gastric ulcer and chronic
      gastritis patients. Giemsa staining, improved Toluidine-blue staining and H
      pylori-specific antibody immune staining were performed as appropriate for the
      histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used
      for the histological diagnosis of activity of H pylori infection, mucosal
      inflammation, glandular atrophy and intestinal metaplasia and scored into four
      grades according to the Updated Sydney System. RESULTS: Total rate of H pylori
      infection, mucosal inflammation, activity of H pylori infection, glandular
      atrophy and intestinal metaplasia in 3 839 gastric ulcer patients (78.5%, 97.4%,
      82.1%, 61.1% and 64.2%, respectively) were significantly higher than those in 4
      102 chronic gastritis patients (55.0%, 90.3%, 56.2%, 36.8%, and 37.0%,
      respectively, P<0.05). The rate of H pylori colonization of chronic gastritis in
      <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age
      groups in antrum was 33.3%, 41.7%, 53.6%, 57.3%, 50.7%, 43.5%, respectively; in
      corpus, it was 32.6%, 41.9%, 53.8%, 60.2%, 58.0%, 54.8%, respectively; in
      angulus, it was 32.4%, 42.1%, 51.6%, 54.5%, 49.7%, 43.5%, respectively. The rate
      of H pylori colonization of gastric ulcer in <30 years, 31-40 years, 41-50 years,
      51-60 years, 61-70 years and >70 years age groups in antrum was 60.5%, 79.9%,
      80.9%, 66.8%, 59.6%, 45.6%, respectively; in corpus, it was 59.7%, 79.6%, 83.6%,
      80.1%, 70.6%, 59.1%, respectively; in angulus, it was 61.3%, 77.8%, 75.3%, 68.8%,
      59.7%, 45.8%, respectively. The rate of H pylori colonization at antrum was
      similar to corpus and angulus in patients, below 50 years, with chronic gastritis
      and in patients, below 40 years, with gastric ulcer. In the other age- groups,
      the rate of H pylori colonization was highest in corpus, lower in antrum and
      lowest in angulus (all P<0.05). The rates of glandular atrophy and intestinal
      metaplasia were higher and earlier in H pylori-positive patients than those
      without H pylori infection (both P<0.01). In comparison of gastric ulcer patients
      with chronic gastritis patients, the rate of glandular atrophy and intestinal
      metaplasia was higher in H pylori-positive patients with gastric ulcer than in H
      pylori-positive patients with chronic gastritis (both P<0.01); the rate of
      glandular atrophy and intestinal metaplasia were also higher in H pylori-negative
      patients with gastric ulcer than in H pylori-negative patients with chronic
      gastritis (both P<0.01). Both glandular atrophy and intestinal metaplasia were
      much more commonly identified in the angulus than in the antrum, lowest in corpus
      (all P<0.01). CONCLUSION: Rate of H pylori infection, glandular atrophy and
      intestinal metaplasia in gastric ulcer were higher than in chronic gastritis in
      all-different age -groups. Distribution of H pylori colonization is pangastric in
      the younger patients. It is highest in corpus, lower in antrum and lowest in
      angulus in the older age groups. Progression of glandular atrophy and intestinal
      metaplasia seem to have a key role in the distribution of H pylori colonization.
      H pylori appears to be the most important risk factor for the development of
      glandular atrophy and intestinal metaplasia, but it is not the only risk.

PMID- 15742401
TI  - Effect of Hewei-Decoction on chronic atrophic gastritis and eradication of
      Helicobacter pylori.
AB  - AIM: To demonstrate the effect of Hewei-Decoction (Decoction for regulating the
      stomach) on chronic atrophic gastritis (CAG) and eradication of Helicobacter
      pylori. METHODS: Ninety patients with CAG entering the investigation were divided
      into six differentiation syndromes, based on their major symptoms and signs.
      Hewei-Decoction was taken by all the patients orally for 4 or 8 wk. The efficacy
      was assessed by both the composite accumulation of reduced scores of major
      symptoms and the eradication of H pylori. chi(2) test was used to compare the
      efficacy between H pylori-positive and negative cases, and to disclose the
      relationship between efficacy and eradication of H pylori. RESULTS: In patients
      with six different syndrome types, the efficacy of Hewei-Decoction was 91.67%
      (11/12), 92.86% (13/14), 97.22% (35/36), 87.50% (14/16), 75.00% (6/8), 75.00%
      (3/4) respectively. The rate of highly efficacious was 58.33% (7/12), 50.00%
      (7/14), 77.78% (28/36), 62.50% (10/16), 12.50% (1/8) and 25.00% (1/4),
      respectively. The total efficacy was 91.11% (82/90), and the rate of highly
      efficacious was 60.00% (54/90). The eradication rate of H pylori was 67.86%
      (38/56). The therapeutic effect of Hewei-Decoction was better in H pylori
      positive cases than that in H pylori-negative cases with the total effect of
      96.43% vs 82.35% (P<0.05). In 56 H pylori positive cases, the therapeutic effect
      was better in H pylori eradicated cases than that in H pylori- existent cases
      with the total effect of 97.37% vs 72.22% (P<0.01). CONCLUSION: Hewei-Decoction
      is effective in most cases of all the syndrome types. The results indicate that
      eradication of H pylori is one of the important mechanisms for alleviation of
      symptoms and signs. Also, the decoction is efficacious in H pylori-negative
      cases.

PMID- 15742400
TI  - Anti-Helicobacter pylori therapy significantly reduces Helicobacter pylori 
      induced gastric mucosal damage in Mongolian gerbils.
AB  - AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pylori therapy on
      the H pylori-infected Mongolian gerbils based on physiological and pathological
      changes. METHODS: We used 6-wk-old male gerbils orally inoculated with H pylori
      (ATCC43504, 2X10(8) CFU/mL). Seven weeks after H pylori inoculation, the animals
      of study group received 4 d' anti-H pylori triple therapy (H pylori-eradicated
      group). Seven days later, all animals of the H pylori-eradicated and control
      groups (H pylori-infected and H pylori-uninfected groups) were sacrificed. We
      examined gastric mucosal lesions macroscopically, studied gastritis
      microscopically and determined the stomach weight ratio, myeloperoxidase (MPO)
      activity and prostaglandin (PG) E(2) level. RESULTS: The results showed that both
      macroscopic and histological gastric damages were significantly less in H pylori
      eradicated group than H pylori-infected group. Stomach weight ratio, MPO activity
      and PGE(2) levels were significantly higher in H pylori-infected group than those
      in the other two groups. CONCLUSION: Four days' anti-H pylori therapy was
      effective in the improvement of H pylori-induced gastric lesions in Mongolian
      gerbils.

PMID- 15742403
TI  - Effect of intestinal ischemia-reperfusion injury on protein levels of leptin and
      orexin-A in peripheral blood and central secretory tissues.
AB  - AIM: To explore the effect of intestinal ischemia-reperfusion injury on protein
      levels of leptin and orexin-A in peripheral blood and their central secretory
      tissues and to find out the role leptin and orexin-A play in acute inflammatory
      responses. METHODS: An intestinal ischemia-reperfusion (I/R) injury model of rats
      was established and rats were divided randomly into six groups: sham-operation
      group, 60 min ischemia/30 min reperfusion group (I60'R30'), I60'R90', I60'R150',
      I60'R240' and I60'R360', 9 rats each group. Two highly-sensitive
      radioimmunoassays for leptin and orexin-A were established and used to check the
      change of their concentrations in peripheral blood and central secretory tissues
      before and after intestinal I/R injury. RESULTS: Compared with the serum leptin
      level before injury, it decreased significantly in I60'R30' group and increased
      significantly in I60'R360' group; compared to sham-operation group after injury,
      serum leptin level increased significantly in I60'R360' group; compared to sham
      operation group after injury, adipose leptin levels decreased significantly in
      I60'R30' and I60'R90' groups, while increased significantly in I60'R360' group.
      There was no significant difference between the expression levels of orexin-A
      before and after I/R injury. CONCLUSION: Leptin has a time-dependent response and
      orexin-A has a delayed response to acute inflammatory stimuli such as intestinal
      I/R injury and they may participate in metabolic disorders in injury as
      inflammatory cytokines.

PMID- 15742402
TI  - A nuclear import inhibitory peptide ameliorates the severity of cholecystokinin
      induced acute pancreatitis.
AB  - AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF
      kappaB) inhibitor peptide PN50 in an experimental model of acute pancreatitis.
      PN50 was produced by conjugating the cell-penetrating penetratin peptide with the
      nuclear localization signal of the NF-kappaB p50 subunit. METHODS: Pancreatitis
      was induced in male Wistar rats by administering 2X100 mug/kg body weight of
      cholecystokinin-octapeptide (CCK) intraperitoneally (IP) at an interval of 1 h.
      PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK
      injections. The animals were sacrificed 4 h after the first injection of CCK.
      RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio,
      serum amylase activity, pancreatic levels of TNF-alpha and IL-6, degree of lipid
      peroxidation, reduced glutathione levels, NF-kappaB binding activity, pancreatic
      and lung myeloperoxidase activity) and morphological parameters of the disease
      were improved before and after treatment with the PN50 peptide. According to the
      histological findings, PN50 protected the animals against acute pancreatitis by
      favoring the induction of apoptotic, as opposed to necrotic acinar cell death
      associated with severe acute pancreatitis. CONCLUSION: Our study implies that
      reversible inhibitors of stress-responsive transcription factors like NF-kappaB
      might be clinically useful for the suppression of the severity of acute
      pancreatitis.

PMID- 15742405
TI  - Acupuncture inhibition on neuronal activity of spinal dorsal horn induced by
      noxious colorectal distention in rat.
AB  - AIM: To observe how acupuncture stimulation influences the visceral nociception
      in rat and to clarify the interactions between acupuncture or somatic input and
      visceral nociceptive inputs in the spinal dorsal horn. These will provide
      scientific base for illustrating the mechanism of acupuncture on visceral pain.
      METHODS: Experiments were performed on Sprague-Dawley rats and the visceral
      nociceptive stimulus was generated by colorectal distention (CRD). Unit
      discharges from individual single neuron were recorded extracellularly with glass
      microelectrode in L(1-3) spinal dorsal horn. Acupuncture stimulation was applied
      at contralateral heterotopic acupoint and ipsilateral homotopic acupoint, both of
      which were innervated by the same segments that innervate also the colorectal
      gut. RESULTS: The visceral nociception could be inhibited at the spinal level by
      the heterotopic somatic mechanical stimulation and acupuncture. The maximal
      inhibition was induced by acupuncture or the somatic noxious stimulation at
      spinal dorsal horn level with inhibiting rate of 68.61% and 60.79%, respectively
      (P<0.01 and <0.001). In reversible spinalized rats (cervical-thoracic cold block)
      both spontaneous activity and responses to CRD increased significantly in 16/20
      units examined, indicating the existence of tonic descending inhibition. The
      inhibition of acupuncture on the noxious CRD disappeared totally in the
      reversible spinalized rats (P<0.001). CONCLUSION: The inputs of noxious CRD and
      acupuncture may interact at the spinal level. The nociceptive visceral inputs
      could be inhibited by acupuncture applied to hetero-topic acupoint. The effect
      indicates that the spinal dorsal horn plays a significant role in mediating the
      inhibition of acupuncture and somatic stimulation on the neuronal response to the
      noxious visceral stimulation and the inhibition is modulated by upper cervical
      cord and/or supra-spinal center.

PMID- 15742404
TI  - Role of adhesion molecules and dendritic cells in rat hepatic/renal ischemia
      reperfusion injury and anti-adhesive intervention with anti-P-selectin lectin-EGF
      domain monoclonal antibody.
AB  - AIM: To investigate the role of P-selectin, intercellular adhesion molecule-1
      (ICAM-1) and dendritic cells (DCs) in liver/kidney of rats with hepatic/renal
      ischemia-reperfusion injury and the preventive effect of anti-P-selectin lectin
      EGF domain monoclonal antibody (anti-PsL-EGFmAb) on the injury. METHODS: Rat
      models of hepatic and renal ischemia-reperfusion were established. The rats were
      then divided into two groups, one group treated with anti-PsL-EGFmAb (n = 20) and
      control treated with saline (n = 20). Both groups were subdivided into four
      groups according to reperfusion time (1, 3, 6 and 24 h). The sham-operated group
      (n = 5) served as a control group. DCs were observed by the microscopic image
      method, while P-selectin and ICAM-1 were analyzed by immunohistochemistry.
      RESULTS: P-selectin increased significantly in hepatic sinusoidal endothelial
      cells and renal tubular epithelial cells 1 h after ischemia-reperfusion, and the
      expression of ICAM-1 was up-regulated in hepatic sinusoid and renal vessels after
      6 h. CD1a(+)CD80(+)DCs gradually increased in hepatic sinusoidal endothelium and
      renal tubules and interstitium 1 h after ischemia-reperfusion, and there was the
      most number of DCs in 24-h group. The localization of DCs was associated with rat
      hepatic/renal function. These changes became less significant in rats treated
      with anti-PsL-EGFmAb. CONCLUSION: DCs play an important role in immune
      pathogenesis of hepatic/renal ischemia-reperfusion injury. Anti-PsL-EGFmAb may
      regulate and inhibit local DC immigration and accumulation in liver/kidney.

PMID- 15742406
TI  - Use of color Doppler ultrasonography in the diagnosis of anomalous connection in
      pancreatobiliary disease.
AB  - AIM: To estimate the detectability of anomalous connection in pancreatobiliary
      disease (ACPBD) cases, measuring gallbladder wall blood flow (GWBF). METHODS: In
      the retrospective study, we enrolled 42 subjects with gallbladder wall
      thickening. GWBF velocity was determined as an average value of the peak velocity
      of color signals on the gallbladder wall, three times in each case. Based on the
      findings on endoscopic ultrasonography (EUS) or endoscopic retrograde
      cholangiopancreatography (ERCP), the 42 subjects were divided into 11 cases with
      ACPBD and 31 cases without ACPBD. In the prospective study, the subjects were 92
      cases with gallbladder wall thickening. Using the cut-off level of the flow
      velocity obtained in the retrospective study, the usefulness of measuring GWBF
      velocity in diagnosing ACPBD was evaluated. RESULTS: In the retrospective study,
      imaging of GWBF was obtained in 40 of the 42 subjects. The mean GWBF velocity of
      the ACPBD cases was 29.4+/-3.9 cm/s (mean+/-SD), which was significantly
      different (P<0.0001; 95% CI 5.48-13.2) from that of the without ACPBD cases
      (20.1+/-5.9 cm/s). Based on this result, we prepared a receiver operating
      characteristic curve, and the cut-off level appropriate for diagnosing ACPBD was
      estimated to be 25 cm/s. In the prospective study, GWBF was detected in 86 of the
      92 subjects. Based on the EUS or ERCP findings, the 92 subjects were divided into
      15 cases with ACPBD and 77 cases without ACPBD. When a cut-off level of 25 cm/s
      was employed, ACPBD could be diagnosed with a sensitivity of 87.0% (13/15) and a
      specificity of 87.3% (62/71). CONCLUSION: Measurement of GWBF velocity, which is
      less invasive and provides objective values, is very useful for diagnosing ACPBD
      prior to the development of malignant tumors in cases with gallbladder wall
      thickening.

PMID- 15742407
TI  - Detection of CK20mRNA in peripheral blood of pancreatic cancer and its clinical
      significance.
AB  - AIM: To detect the expression of CK20mRNA in peripheral blood of pancreatic
      cancer and evaluate its clinical significance. METHODS: Expression of CK20mRNA in
      peripheral blood was detected by fluorogenic qualitative reverse transcription
      polymerase chain reaction (RT-PCR) in 40 cases of pancreatic cancer at the night
      before operation, in 5 cases of benign pancreatic diseases, in 5 cases of healthy
      individuals. The relationships were investigated between CK20mRNA expression and
      the clinicopathological variables, and clinical follow-up outcome in those
      patients with pancreatic cancer having undergone radical resection. RESULTS: Of
      the 40 patients with pancreatic cancer, 23 (57.5%) cases were positive for
      CK20mRNA expression. CK20mRNA expression was significantly correlated with
      lymphatic metastasis (P = 0.008), histopathological grading (P = 0.009), and
      pathological stage (P = 0.021); there was no significant correlation between
      CK20mRNA expression and age, gender, tumor diameter, and depth of invasion. The
      cumulative metastasis rates of patients with CK20mRNA expression were higher than
      those of patients with no CK20mRNA expression within 6 mo (34.7% vs 5.9%, P =
      0.043) or 12 mo (73.9% vs 35.3%, P = 0.02) after operation. CK20mRNA expression
      in peripheral blood of pancreatic cancer indicated poorer prognosis. The survival
      rate of patients with CK20mRNA expression was lower than that of patients with
      negative CK20mRNA expression (Log-Rank = 13.31, P = 0.0003). CONCLUSION: CK20mRNA
      is a sensitive and specific molecular marker for the detection of micrometastasis
      in peripheral blood of patients with pancreatic cancer. The CK20mRNA expression
      in peripheral blood is correlated with biological characteristic of pancreatic
      cancer. It can help to predict the prognosis of pancreatic cancer after
      operation, and to determine which patient will benefit from aggressive adjuvant
      therapies.

PMID- 15742408
TI  - Childhood inflammatory bowel disease: parental concerns and expectations.
AB  - AIM: To document the concerns and expectations of parents of children with
      inflammatory bowel disease (IBD) within the context of a multidisciplinary IBD
      clinic, and to highlight the importance of a holistic approach to the care of
      these children. METHODS: The parents of 60 children with IBD were surveyed by
      mailed questionnaire. Parents were asked to provide details of their concerns
      regarding their child's condition and to express their expectations of medical
      care. In addition, enquiry was made in respect to the respondents' learning about
      IBD. RESULTS: Forty-six questionnaires (77%) returned. Fifty-two percent of the
      patients were male. Patients were aged a mean of 10.9 (+/-4.1) years and
      diagnosed at an average age of 2.1 (+/-1.8) years previously. The most common
      concerns expressed by the parents related to the side- effects of medications and
      the future prospects for their child. Overall, parents were satisfied with
      aspects of care within the IBD clinic but many suggested additional personnel
      such as counselors or educators should be available. Parents also reported the
      need for continuing education and easy access to up-to-date information.
      CONCLUSION: Parents of children and adolescents with IBD have many common
      concerns regarding their child's condition. On-going attention to holistic care,
      including psychosocial and educational elements for patients and families, is
      appropriate in the context of the chronic and unpredictable nature of IBD.

PMID- 15742410
TI  - Immune response to an indigenously developed r-hepatitis B vaccine in mixed
      population: study of an accelerated vaccination schedule.
AB  - AIM: To establish the safety and efficacy of an indigenously developed r
      hepatitis B vaccine using an accelerated schedule and to highlight the social
      awareness and commitment in preventing the spreading of hepatitis B virus
      infection. METHODS: The study was a multicentric, double blind, randomized (3:1)
      study using three doses of vaccine immunization schedule (20 mug for those above
      10 years old and 10 mug for those below 10 years old) on d 0, 30 and 60. One
      hundred and sixty-six subjects were enrolled (87 males and 76 females aged 5-35
      years). The main outcome measure was assessment of immunogenicity and safety.
      RESULTS: A 100% seroconversion response was observed on the 30(th) d after the
      1(st) injection in both the experimental groups. The sero-protection data
      reported a 41.2-65.6% response on the 30(th) d after the 1(st) injection and
      reached 100% on the 60(th) d. Descriptive statistical analysis showed a geometric
      mean titer value of 13.77 mIU/mL in the test (BEVAC) group and 10.95 mIU/mL in
      the commercial control (ENGERIX-B) group on the 30(th) d after the 1(st)
      injection. The response on the 60(th) d showed a geometric mean titre value (GMT)
      of 519.84 mIU/mL in the BEVAC group and 475.46 mIU/mL in the ENGERIX-B group. On
      the 90(th) d, the antibody titer response was observed to be 2627.58 mIU/mL in
      the BEVAC group and 2272.72 mIU/mL in the ENGERIX-B group. Two subjects in each
      group experienced pains at injection site after the first vaccination. A total of
      six subjects in both groups experienced a solicited adverse reaction, which
      included pains, swelling and redness at the injection site, three subjects in the
      group-B had a pain at the injection site after the third dose. No other serious
      adverse events occurred and no dose-related local or general symptoms were
      observed during the study. CONCLUSION: The vaccine is safe, efficacious and
      immunogenic in comparison with the well documented ENGERIX-B.

PMID- 15742409
TI  - Helicobacter pylori infection and low serum pepsinogen I level as risk factors
      for gastric carcinoma.
AB  - AIM: To study whether examination of CagA antibodies could increase the odds
      ratio for gastric cancer in a case-control study, and how often other serum
      markers of gastric cancer risk could be found in Helicobacter pylori -negative
      patients. METHODS: H pylori CagA and parietal cell antibodies (PCAs), and serum
      pepsinogen I (SPGI) levels were compared between patients with gastric cancer and
      controls who received endoscopic examination due to reasons other than
      gastrointestinal malignancy. RESULTS: The odds ratio (OR) for gastric cancer was
      2.9 (95% CI 1.4-5.8) in H pylori + patients, and 2.4 (95% CI 1.2-4.9) in CagA+
      patients. When results of H pylori and CagA antibodies were combined, OR
      increased to 5.0 (95% CI 2.5-10.0). Furthermore, if cardia cancer patients were
      excluded, the OR increased to 6.8 (95% CI 3.1-14.8). Among patients with a low
      SPGI level, the OR was 12.0 (95% CI 4.1-35.3). However, the risk was significant
      only in the older age group. The number of patients with low SPGI was
      significantly higher in H pylori -/CagA+ patients as compared to other cancer
      patients. CONCLUSION: Examination of both H pylori and CagA antibodies increases
      the OR for gastric cancer in our case-control study. CagA antibodies are
      important in detecting previous H pylori infection in advanced atrophic gastritis
      or cancer when spontaneous decline of H pylori antibodies occurs. SPGI may be
      helpful in screening elderly gastric cancer patients.

PMID- 15742411
TI  - Inhibitory effect of fluvastatin on ileal ulcer formation in rats induced by
      nonsteroidal antiinflammatory drug.
AB  - AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage
      as one of their side effects in humans and experimental animals. Lipid
      peroxidation plays an important role in NSAID-induced ulceration. The aim of this
      study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors on the ulceration in small intestines
      of rats. METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin,
      pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4
      fluorophenyl)-3-(4- methylsulfonylphenyl) thiophene (BFMeT)-treated rats were
      examined. Antioxidative activity of the inhibitors was measured by a redox-linked
      colorimetric method. RESULTS: Fluvastatin, which was reported to have
      antioxidative activity, repressed the ileal ulcer formation in rats treated with
      BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and
      atorvastatin) did not repress the ileal ulcer formation. Among these HMG-CoA
      reductase inhibitors, fluvastatin showed a significantly stronger reducing power
      than the others (pravastatin, atorvastatin). CONCLUSION: Fluvastatin having the
      antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.

PMID- 15742412
TI  - Epinephrine injection therapy versus a combination of epinephrine injection and
      endoscopic hemoclip in the treatment of bleeding ulcers.
AB  - AIM: To assess the efficacy of hemoclip application in combination with
      epinephrine injection in the treatment of bleeding peptic ulcers and to compare
      the clinical outcomes between patients treated with such a combination therapy
      and those treated with epinephrine injection alone. METHODS: A total of 293
      patients (211 males, 82 females) underwent endoscopic therapy for bleeding peptic
      ulcers. Of these, 202 patients (152 males, 50 females) received epinephrine
      injection therapy while 91 patients (59 males, 32 females) received combination
      therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic
      rates, rebleeding rates, need for emergency surgery and 30-d mortality were the
      outcome measures studied. RESULTS: Patients who received combination therapy were
      significantly older (mean age 66+/-16 years, range 24-90 years) and more suffered
      from chronic renal failure compared to those who received epinephrine injection
      therapy alone (mean age 61+/-17 years, range 21-89 years). Failure to achieve
      permanent hemostasis was 4% in the group who received epinephrine injection alone
      and 11% in the group who received combination therapy. When the differences in
      age and renal function between the two treatment groups were taken into account
      by multivariate analysis, the rates of initial hemostasis, rebleeding rates, need
      for surgery and 30-d mortality for both treatment options were not significantly
      different. CONCLUSION: Combination therapy of epinephrine injection with
      endoscopic hemoclip application is an effective method of achieving hemostasis in
      bleeding peptic ulcer diseases. However, superiority of combination therapy over
      epinephrine injection alone, could not be demonstrated.

PMID- 15742413
TI  - Response of blood endothelin-1 and nitric oxide activity in duodenal ulcer
      patients undergoing Helicobacter pylori eradication.
AB  - AIM: To investigate the effect of Helicobacter pylori eradication on endothelin-1
      (ET-1) and nitric oxide (NO) in duodenal ulcer (DU) patients. METHODS: Sixty-six
      H pylori-infected active DU patients were consecutively enrolled to receive one
      week triple therapy (rabeprazole, amoxicillin and metronidazole) and then one
      month rabeprazole therapy. They were asked back to determine ulcer and H pylori
      status using endoscopy one month later. Thirty-seven healthy controls (H pylori
      +/-: 17/20) were enrolled for comparison. Blood samples were collected in each
      visit to measure plasma ET-1 and nitrate/nitrite levels using an enzyme
      immunoassay kit. RESULTS: Sixty DU patients finished trial per protocol. The
      ulcer healing and H pylori-eradication rates were 86.7% and 83.3%, respectively.
      Plasma ET-1 level in DU patients was higher than that of H pylori-negative and
      positive controls (3.59+/-0.96 vs 0.89+/-0.54 vs 0.3+/-0.2 pg/mL, P<0.01), while
      nitrate/nitrite levels among them were also significantly different (8.55+/-0.71
      vs 5.27+/-0.68 vs 6.39+/-0.92 mumol/L, P<0.05). H pylori eradication diminished
      ET-1 levels (3.64+/-0.55 vs 2.64+/-0.55 pg/mL, P<0.01) but elevated
      nitrate/nitrite level (8.16+/-0.84 vs 11.41+/-1.42 mumol/L, P<0.05). CONCLUSION:
      Both plasma ET-1 and nitrate/nitrite levels increase in active DU patients. After
      an effective H pylori eradication, DU healing is associated with diminished blood
      ET-1 level and elevated nitrate/nitrite level.

PMID- 15742414
TI  - Analysis of CD117-negative gastrointestinal stromal tumors.
AB  - AIM: To identify the gastrointestinal stromal tumors (GISTs) that are negative
      for CD117 expression by immunohistochemistry and to characterize their malignant
      potential. METHODS: A total of 108 primary mesenchymal tumors of the
      gastrointestinal tract were screened to select CD117-negative tumors, from which
      KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 10, 12, 14, and 18) were
      sequenced to identify GISTs. Tumor recurrence and distant metastasis were used as
      the criteria of malignancy. RESULTS: The result showed that approximately 25%
      (29/108) of the gastrointestinal mesenchymal tumors were negative for CD117 and
      approximately 6% (7/108) of the tumors were CD117-negative GISTs. All these CD117
      negative tumors had a mutated KIT and a wild-type PDGFRA. All CD117-negative
      GISTs with mutations at codons 557/558 of KIT had mitotic counts >10/50 high
      power field, and 75% (3/4) of them showed multiple recurrence or distant
      metastasis. CONCLUSION: CD117-negative KIT mutated GISTs account for
      approximately 6% of the gastrointestinal mesenchymal tumors. Tumor recurrence or
      distant metastasis correlates to both the KIT mutations at codons 557/558 and the
      mitotic counts, but not to the tumor size.

PMID- 15742415
TI  - Correlation between clinicopathology and expression of heat shock protein 70 and
      glucose-regulated protein 94 in human colonic adenocarcinoma.
AB  - AIM: To investigate the correlation between clinicopathology and expression of
      heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human
      colonic carcinoma. METHODS: The expression of HSP70 and grp94 was studied in 80
      human colonic cancers with or without metastasis as well as in their adjacent
      mucous membrane by way of immunohistochemistry and pathology photograph analysis.
      RESULTS: The expression of HSP70 and grp94 was significantly higher in cancer
      than that in adjacent mucous membrane (92.5%, 85.0% vs 56.3%, 42.5%, P<0.01).
      HSP70 and grp94 expressed higher in moderately- and poorly-differentiated colonic
      cancers than that in their adjacent tissues (93.7%, 87.5%; 100%, 90% vs 56.3%,
      42.5%; P<0.01). Dukes C and D stages of colonic cancers showed higher positive
      rates than Dukes A and B stage groups (97.1%, 91.2%; 100%, 90.9%; vs 80%, 70%;
      78.6%, 71.4%; P<0.05). There were definite differences in HSP70 and grp94
      expression between metastasis groups and non-metastasis groups (100% vs 75%, 100%
      vs 50%, P<0.05). CONCLUSION: The HSP70 and grp94 expression rates in colonic
      cancer groups are significantly higher than that in their adjacent mucous
      membrane. The HSP70 and grp94 expression in poorly-differentiated colonic cancers
      with metastasis is significantly higher than well-differentiated cancers without
      metastasis. The overexpression of HSP70 and grp94 can be used as diagnostic or
      prognostic markers for colonic cancer.

PMID- 15742416
TI  - Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo.
AB  - AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR)
      of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER).
      METHODS: Multidrug resistance was determined by means of semi-quantitative retro
      transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER
      expression was studied by immunohistochemistry. Tumor tissues from three cases of
      human colon carcinoma, which had mdr1(+)/ER(+), mdr1(+)/ER(-), mdr1(-)
      expressions, were planted subcutaneously in the neck of nude mice to establish
      three xenograft models. These models were subdivided into four subgroups
      randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group
      and control group. The dimensions of these xenografts were measured after each
      course of treatment and the xenografts were removed at the end of the experiments
      for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In
      each course, TAM (15 mg/(kg/d)) was administrated orally per day in the first
      seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data
      was evaluated by q and t tests. RESULTS: In the animal models with mdr1(-) tumor,
      the weights and volumes of the planted tumor in DOX group ((39.1+/-2.29) mg,
      (31.44+/-1.61) mm(3)) and TAM and DOX group ((38.72+/-2.56) mg, (31.31+/-1.74)
      mm(3)), which were lesser than that of control group ((45.48+/-3.92) mg, (36.42+/
      2.77)mm(3), P = 0.037, P = 0.016 respectively) significantly. In the animal
      models with mdr1(+)/ER(+) tumor, the weights and volumes of planted tumor were
      not affected by DOX or TAM treatment; however, in TAM and DOX group ((425.5+/
      28.58) mg, (340.35+/-22.28) mm(3)), they were significantly less than that of
      control group ((634.23+/-119.41) mg, (507.45+/-93.34) mm(3), P = 0.022, P = 0.045
      respectively), which are similar to that in the models with mdr1(+)/ER(-) tumor.
      No significant changes were found in the expressive level of mdr1 mRNA following
      these treatments. CONCLUSION: The expression of mdr1 gene corresponds to the
      sensitivity of colon cancer to anti-tumor drugs in vivo. TAM can reverse the MDR
      of colorectal carcinoma in nude mice, which is independent of the expression of
      ER; however, no change was observed in the expressive level of mdr1 mRNA.

PMID- 15742417
TI  - Adenovirus mediated CTLA4Ig gene inhibits infiltration of immune cells and cell
      apoptosis in rats after liver transplantation.
AB  - AIM: To investigate the role of adenovirus-mediated CTLA4Ig gene therapy in
      inhibiting the infiltration of macrophages and CD8(+) T cells and cell apoptosis
      after liver transplantation. METHODS: The rat orthotopic liver transplantation
      model was applied. The rats were divided into three groups: group I: rejection
      control (SD-to-Wistar); group II: acute rejection treated with intramuscular
      injection of CsA 3.0 mg/(kg x d) for 12 d (SD-to-Wistar+CsA); groupIII: injection
      of 1 x 10(9) PFU adenovirus-mediated CTLA4Ig gene liquor in dorsal vein of penis
      7 d before liver transplantation (SD-to-Wistar+CTLA4Ig). Immunohistochemistry and
      transferase-mediated dUTP nick-end labeling (TUNEL) were used to analyze the
      expression of CTLA4Ig gene in liver, infiltration of macrophages and CD8(+) T
      cells, cell apoptosis in grafts at different time-points after liver
      transplantation. Histopathological examination was done. RESULTS: CTLA4Ig gene
      expression was positive in liver on d 7 after administering adenovirus-mediated
      CTLA4Ig gene via vein, and remained positive until day 60 after liver
      transplantation. Infiltration of macrophages and CD8(+) T cells in CTLA4Ig
      treated group was less than in rejection control group and CsA-treated group. The
      apoptotic index of rejection group on d 3, 5, and 7 were significantly higher
      than that of CTLA4Ig-treated group. A good correlation was found between severity
      of rejection reaction and infiltration of immune activator cells or cell
      apoptotic index in grafts. CONCLUSION: CTLA4Ig gene is constantly expressed in
      liver and plays an important role in inducing immune tolerance.

PMID- 15742418
TI  - L-arginine administration ameliorates serum and pulmonary cytokine response after
      gut ischemia-reperfusion in immature rats.
AB  - AIM: Small intestinal ischemia-reperfusion (IR) has been demonstrated to result
      in both local mucosal injury and systemic injuries. The exact role of nitric
      oxide (NO) in intestinal IR is unclear. We propose that NO and some other
      cytokines change in the reperfusion period and these changes are associated with
      lung injury. The aim of this study was to determine the effect of supplementing
      NO substrate, L-arginine (L-arg), on serum and pulmonary cytokine production
      during small intestinal IR in immature rats. METHODS: Immature rats underwent 60
      min. of superior mesenteric artery occlusion followed by 90 min of reperfusion. L
      arg (250 mg/kg) was given intravenously to the experimental group (IR+L-arg)
      which received L-arg after 45 min of intestinal ischemia. Serum and lung
      endothelin-1 (ET-1), NO, malondialdehyde (MDA), and tumor necrosis factor alpha
      (TNFalpha) were measured. Sham operation (SHAM) and intestinal IR (IR) groups
      were performed as control. The lavage fluid of the lung was collected by
      bronchoalveolar lavage (BAL) and white blood cells and polymorphonuclear cells
      (PMNs) were immediately counted to identify lung damage. RESULTS: When L-arg was
      given during small intestinal IR, serum NO concentration increased significantly
      in IR+L-arg group (162.17+/-42.93 micromol/L) when compared with IR group
      (87.57+/-23.17 micromol/L, t = 3.190, P = 0.008<0.01). Serum MDA reduced
      significantly in IR+L-arg group (8.93+/-1.50 nmol/L) when compared with SHAM
      (23.78+/-7.81 nmol/L, t = 3.243, P = 0.007<0.01) and IR (25.54+/-9.32 nmol/L, t =
      3.421, P = 0.006<0.01). ET-1 level in lung tissues was significantly lower in
      IR+L-arg group (13.81+/-7.84 pg/mL) than that in SHAM (35.52+/-10.82 pg/mL, t =
      2.571, P = 0.03<0.05) and IR (50.83+/-22.05 pg/mL, t = 3.025, P = 0.009<0.01)
      groups. MDA contents in lung tissues were significantly lower in IR+L-arg group
      (10.73+/-1.99 nmol/L) than in SHAM (16.62+/-2.28 nmol/L, t = 3.280, P =
      0.007<0.01) and IR (21.90+/-4.82 nmol/L, t = 3.322, P = 0.007<0.01) groups. Serum
      and lung TNFalpha concentrations were not significantly different in three
      groups. NO contents in lung homogenates and white blood cell counts in BAL had no
      significant difference in three groups; but the percentage of PMNs in BAL was
      13.50+/-8.92, 33.20+/-16.59, and 22.50+/-6.09 in SHAM, IR, and IR+L-arg groups,
      respectively. CONCLUSION: Small intestinal IR induced increases of pulmonary
      neutrophil infiltration in immature rats. Neutrophil infiltration in lung tissues
      was reduced by L-arg administration but remained higher than in SHAM group. L-arg
      administration during intestinal IR enhances serum NO production, reduces serum
      MDA and lung ET-1 and MDA levels, resulting in the improvement of systemic
      endothelial function. L-arg supplementation before reperfusion may act as a
      useful clinical adjunct in the management of intestinal IR, thus preventing the
      development of adult respiratory distress syndrome, even multiple organ
      dysfunction syndrome (MODS).

PMID- 15742419
TI  - Comparison of integrated Chinese and Western medicine with and without
      somatostatin supplement in the treatment of severe acute pancreatitis.
AB  - AIM: To evaluate the therapeutic effect of the combined use of early short-term
      somatostatin and conventional integrated Chinese and Western medicine in treating
      severe acute pancreatitis. METHODS: Sixty patients with severe acute pancreatitis
      were divided at random into a somatostatin group and a basic treatment group.
      Both groups received integrated traditional Chinese and Western medicine without
      surgery. For patients in the somatostatin group, somatostatin was infused
      intravenously 250 microg/h for 72 h; other medications were the same as in the
      basic treatment group. In both groups, comparisons of therapeutic effectiveness
      were made in terms of morbidity of organic dysfunction and mortality rate, and
      severity of the disease according to serum levels of C-reaction protein, scores
      of acute physiology and chronic health evaluation (APACHE II), and scores of
      Balthazar-CT. RESULTS: The indexes for C-reaction protein levels on the fourth
      and seventh days, and APACHE II scores on the seventh day after treatment, were
      significantly improved in the somatostatin group than in the basic treatment
      group. The morbidity of organic dysfunction was lower in the somatostatin group
      than in the basic treatment group, although the difference was not statistically
      significant. There was no significant difference in mortality between the two
      groups. CONCLUSION: We conclude that combined traditional Chinese and Western
      medicines with an early short-term use of somatostatin can improve the condition
      of patients with severe acute pancreatitis.

PMID- 15742420
TI  - Solubility of disulfide-bonded proteins in the cytoplasm of Escherichia coli and
      its "oxidizing" mutant.
AB  - AIM: To study the influence of redox environment of Escherichia coli (E. coli)
      cytoplasm on disulfide bond formation of recombinant proteins. METHODS: Bovine
      fibroblast growth factor (BbFGF) was selected as a model of simple proteins with
      a single disulfide bond and free cysteines. Anti-HBsAg single-chain Fv (HBscFv),
      an artificial multidomain protein, was selected as the model molecule of complex
      protein with 2 disulfide bonds. A BbFGF-producing plasmid, pJN-BbFGF, and a
      HBscFv producing-plasmid, pQE-HBscFv, were constructed and transformed into E.
      coli strains BL21(DE3) and M15(pREP4) respectively. At the same time, both
      plasmids were transformed into a reductase-deficient host strain, E. coli
      Origami(DE3). The 4 recombinant E. coli strains were cultured and the target
      proteins were purified. Solubility and bioactivity of recombinant BbFGF and
      HBscFv produced in different host strains were analyzed and compared
      respectively. RESULTS: All recombinant E. coli strains could efficiently produce
      target proteins. The level of BbFGF in BL21(DE3) was 15-23% of the total protein,
      and was 5-10% in Origami (DE3). In addition, 65% of the BbFGF produced in
      BL21(DE3) formed into inclusion body in the cytoplasm, and all the target
      proteins became soluble in Origami(DE3). The bioactivity of BbFGF purified from
      Origami(DE3) was higher than its counterpart from BL21(DE3). The ED(50) of BbFGF
      from Origami(DE3) and BL21(DE3) was 1.6 microg/L and 2.2 microg/L, respectively.
      Both HBscFv formed into inclusion body in the cytoplasm of M15(pQE-HBscFv) or
      Origami(pQE-HBscFv). But the supernatant of Origami(pQE-HBscFv) lysate displayed
      weak bioactivity and its counterpart from M15(pQE-HBscFv) did not display any
      bioactivity. The soluble HBscFv in Origami(pQE-HBscFv) was purified to be 1-2
      mg/L and its affinity constant was determined to be 2.62 x 10(7) mol/L. The yield
      of native HBscFv refolded from inclusion body in M15(pQE-HBscFv) was 30-35 mg/L
      and the affinity constant was 1.98 x 10(7) mol/L. There was no significant
      difference between the bioactivity of HBscFvs refolded from the inclusion bodies
      produced in different host strains. CONCLUSION: Modification of the redox
      environment of E. coli cytoplasm can significantly improve the folding of
      recombinant disulfide-bonded proteins produced in it.

PMID- 15742421
TI  - Effects of killing Helicobacter pylori quadruple therapy on peptic ulcer: a
      randomized double-blind clinical trial.
AB  - AIM: To study the therapeutic efficacy of a Chinese and Western integrated
      regimen, killing Helicobacter pylori quadruple therapy on H pylori-associated
      peptic ulcers (PU). METHODS: With prospective and double-blind controlled method,
      seventy-five active PU patients with H pylori infection were randomized to
      receive one of the following three regimens: (1) new triple therapy (group A:
      lansoprazole 30 mg qd, plus clarithromycin 250 mg bid, plus amoxycillin 500 mg
      tid, each for 10 d); (2) killing Hp quadruple therapy(group B: the three above
      drugs plus killing H pylori capsule 6 capsules bid for 4 wk) and (3)
      placebo(group C: gastropine 3 tablets bid for 4 wk). H pylori eradication and
      ulcer healing quality were evaluated under an endoscope 4 wk after treatment. The
      patients were followed up for 5 years. RESULTS: Both the healing rate of PU and H
      pylori eradication rate in group B were significantly higher than those in group
      C (100% and 96.4% vs 20% and 0%, respectively, P<0.005), but there was no
      significant difference compared to those in group A (88% and 92%, P>0.05). The
      healing quality of ulcer in group B was superior to that in groups C and A
      (P<0.05). The recurrence rate of PU in group B (4%) was lower than that in group
      A (10%) and group C (100%, P<0.01). CONCLUSION: Killing Helicobacter pylori
      quadruple therapy can not only promote the eradication of H pylori and healing
      quality of ulcer but also reduce recurrence rate of ulcer.

PMID- 15742422
TI  - Clinical outcomes of enteroscopy using the double-balloon method for strictures
      of the small intestine.
AB  - AIM: To evaluate the clinical outcome of enteroscopy, using the double-balloon
      method, focusing on the involvement of neoplasms in strictures of the small
      intestine. METHODS: Enteroscopy, using the double-balloon method, was performed
      between December 1999 and December 2002 at Jichi Medical School Hospital, Japan
      and strictures of the small intestine were found in 17 out of 62 patients. These
      17 consecutive patients were subjected to analysis. RESULTS: The double-balloon
      enteroscopy contributed to the diagnosis of small intestinal neoplasms found in 3
      out of 17 patients by direct observation of the strictures as well as biopsy
      sampling. Surgical procedures were chosen for these three patients, while balloon
      dilation was chosen for the strictures in four patients diagnosed with
      inflammation without involvement of neoplasm. CONCLUSION: Double-balloon
      enteroscopy is a useful method for the diagnosis and treatment of strictures in
      the small bowel.

PMID- 15742423
TI  - Thrombosis and inflammation: a question in need of an answer.

PMID- 15742424
TI  - Study eligibility criteria: the perils of feasibility based decision making.

PMID- 15742426
TI  - Trial of tramadol/acetaminophen tablets for osteoarthritis pain in subjects
      receiving a COX-2 nonsteroidal antiinflammatory drug.

PMID- 15742427
TI  - Subgroups within "nonspecific" low back pain.

PMID- 15742428
TI  - Phospholipase A2: quo vadis?

PMID- 15742429
TI  - Osteopontin gene polymorphisms in Spanish patients with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology
      characterized by cartilage and bone destruction. The main genetic determinant to
      RA, the shared epitope, maps to the HLA-DR locus, although this is not the only
      risk factor. The osteopontin (OPN) gene, with pleiotropic functions in
      inflammatory and immune responses, has been implicated in the pathogenesis of RA.
      We studied the association of polymorphisms in the OPN gene and predisposition to
      RA. METHODS: Analysis was performed in a case-control study with 263 patients and
      478 controls. Four single nucleotide polymorphisms (SNP), 327T/C, 795C/T,
      1128A/G, and 1284A/C, of the OPN gene were genotyped by primer-specific
      amplification in the presence of SYBR Green. RESULTS: Distorted transmission of
      these polymorphisms was studied in 58 RA trios and 61 affected sibling pairs.
      These SNP demonstrated strong linkage disequilibrium. No statistically
      significant association was observed (80% power to exclude a genotypic relative
      risk of 1.49 at the 5% significance level, with minor allele frequencies of 28%).
      This lack of association with RA was found after stratification for the shared
      epitope as well. CONCLUSION: Our data suggest that, unlike the reported effect of
      the OPN SNP conferring predisposition to common diseases such as multiple
      sclerosis or systemic lupus erythematosus, these OPN gene polymorphisms do not
      contribute to RA susceptibility in the Spanish population we studied.

PMID- 15742430
TI  - Overexpression of osteopontin in rheumatoid synovial mononuclear cells is
      associated with joint inflammation, not with genetic polymorphism.
AB  - OBJECTIVE: Osteopontin (OPN) is thought to play an important role in rheumatoid
      synovitis. We investigated the expression of OPN in rheumatoid synovial fluid
      mononuclear cells (SFMC) and its potential association with genetic polymorphism
      of the OPN gene and joint inflammation in rheumatoid arthritis (RA). METHODS: 1.
      The expression of OPN mRNA in peripheral blood mononuclear cells (PBMC) and SFMC
      of patients with RA was analyzed quantitatively by real-time polymerase chain
      reaction (PCR). Results were analyzed in paired PBMC and SFMC and control PBMC.
      2. Six single nuclear acid polymorphisms of the OPN gene were genotyped in a
      cohort of 192 Chinese patients with RA and controls (n = 288) by restriction
      fragment length polymorphism PCR or direct DNA sequencing. 3. SF derived from RA
      patients was examined for the stimulating effect on mRNA expression of the OPN
      gene in PBMC. RESULTS: The expression of OPN gene was significantly increased in
      SFMC and, to a lesser degree, in PBMC of patients with RA compared to control
      PBMC (p < 0.01). However, the prevalence of OPN genotype and allele frequencies
      at the selected positions did not differ significantly between RA patients and
      the control group (p > 0.05). Further characterization indicated that SF known to
      contain a variety of proinflammatory factors significantly stimulated mRNA
      expression of OPN in PBMC obtained from RA patients or healthy controls.
      CONCLUSION: Overexpression of OPN mRNA in SFMC is associated with proinflammatory
      factors produced in inflamed joints, but not with OPN genetic polymorphisms. OPN
      gene polymorphisms do not correlate with susceptibility to RA.

PMID- 15742431
TI  - A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a
      selective inhibitor of group II secretory phospholipase A2, in the treatment of
      rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a selective inhibitor of
      secretory phospholipase (sPLA2), LY333013, in the treatment of rheumatoid
      arthritis (RA). METHODS: Two hundred and fifty-one patients with active RA
      despite treatment with one or more disease modifying antirheumatic drugs (DMARD)
      received oral doses of LY333013 (50, 250, and 1000 mg) or placebo once daily for
      12 weeks. Concomitant low-dose glucocorticoids (< or = 10 mg/day prednisone
      equivalent) were allowed. Clinical improvement was assessed using the response
      criteria of the American College of Rheumatology (ACR20), and safety was
      evaluated with respect to adverse events and laboratory test abnormalities.
      RESULTS: The demographic characteristics of the treatment groups were similar.
      Dose-response relationships were found for ACR20 responses (p = 0.058) and
      reductions in C-reactive protein (p = 0.058) at week 1. The proportions of
      patients with an ACR20 response subsequently increased in all study groups
      including the placebo group at weeks 4 and 8, and the initial treatment benefit
      was lost. Adverse events were generally mild in severity and not associated with
      treatment. CONCLUSION: Treatment with LY333013 for 12 weeks was well tolerated
      but ineffective as an adjunct to DMARD treatment of active RA.

PMID- 15742433
TI  - Prediction of mortality in rheumatoid arthritis based on disease activity
      markers.
AB  - OBJECTIVE: The risks and predictors for mortality in patients with rheumatoid
      arthritis (RA) were examined in a cohort of 152 consecutive outpatients (119
      women, 33 men) seen in a 2 month period. METHODS: We evaluated 4 measures of
      disease activity: erythrocyte sedimentation rate (ESR), physician and patient
      global assessment of disease activity, and the Ritchie Articular Index (RAI) as
      mortality predictors, adjusting for disease severity, treatment, and
      cardiovascular disease (CVD) comorbidity. RESULTS: During followup from 1978
      through 1998, 111 patients (86 women, 25 men) died, and only one was lost to
      followup. The standardized mortality ratio for women was 161 (95% confidence
      interval 129-199), for men 152 (95% CI 99-223), and for both sexes combined 156
      (95% CI 128-188). In a proportional hazards model adjusted for age and sex, at
      the beginning of the period and for the whole group, significant predictors of
      mortality were Steinbrocker functional class, Larsen index, CVD comorbidity, use
      of corticosteroids ever, ESR, and the physician and patient global assessment of
      disease activity; but the rheumatoid factor (RF), RAI, and use of disease
      modifying antirheumatic drugs were not significant predictors. When evaluating
      the 4 assessments of disease activity adjusting for confounders, only physician
      global assessment hazard ratio (HR) = 1.32 per 1 SD (95% CI 1.00-1.74) and ESR HR
      = 1.47 per 1 SD (95% CI 1.11-1.93) were significant predictors. CONCLUSION: This
      longterm followup study of a single clinical patient cohort showed a significant
      increase in mortality among patients with RA compared to the general population
      in Malmo. In addition to disease damage and CVD comorbidity, measures of disease
      activity independently predicted mortality, which supports the hypothesis that
      improving these variables may also improve longterm outcome.

PMID- 15742432
TI  - Detection of the p53 regulator murine double-minute protein 2 in rheumatoid
      arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by hyperplasia of synovial
      lining tissue, which is involved directly in the damage of cartilage and bone.
      One of the factors thought to contribute to this synovial lining hyperplasia is
      dysregulation of, or functional abnormality in, the tumor suppressor protein p53.
      The protein known as murine double-minute protein 2 (MDM2) is the major negative
      regulator of p53, and in tumors contributes to increased cell proliferation. The
      detection of MDM2 in rheumatoid synovium has not previously been described. We
      investigated whether this protein is detectable in cells and tissues derived from
      patients with RA. METHODS: Expression of MDM2 protein was examined in fibroblast
      like synoviocytes (FLS) by methods including permeabilization flow cytometry,
      immunofluorescence, and Western blotting, and in synovial tissues using
      immunohistochemistry. The proliferative capacity of these cells was also examined
      using 3H/thymidine incorporation. Cell cycle analysis was performed by propidium
      iodide incorporation. RESULTS: MDM2 was detected in RA FLS and synovial tissues.
      MDM2 protein was identified in CD14-positive and CD14-negative synovial lining
      cells and CD14-positive sublining cells. RA FLS exhibited faster proliferative
      rates and higher levels of MDM2 expression than FLS derived from patients with
      osteoarthritis (OA). Both OA and RA FLS were found to be in similar phases of the
      cell cycle at the time of MDM2 protein analysis. CONCLUSION: The abundant
      expression of MDM2 in RA may be a contributing factor to the hypoapoptotic
      phenotype of lining tissue through its capacity to downregulate p53 levels and
      effects. Further studies are required to determine the relationship between this
      cell-cycle protein profile, tissue hyperplasia, and the functional abnormality of
      p53 in RA.

PMID- 15742434
TI  - Traditional and nontraditional cardiovascular risk factors are associated with
      atherosclerosis in rheumatoid arthritis.
AB  - OBJECTIVE: To determine the association between cardiovascular (CV) risk factors
      and atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: The
      common carotid artery intima-media thickness (IMT) and plaque were evaluated by
      high resolution B-mode ultrasound in 74 consecutive patients with RA. Patients
      with an IMT > or = 0.60 mm and plaque were considered to have atherosclerosis and
      advanced atherosclerosis, respectively. Traditional risk factors as well as an
      extensive range of other clinical and laboratory variables were recorded. Methods
      used to analyze the data included logistic regression, classification and
      regression tree (CART), and factor analyses. RESULTS: Fifty-three (72%) patients
      had atherosclerosis, 23 (31%) had plaque, and 21 (28%) were free of
      atherosclerosis. In multivariable analysis, age and hypertension were
      independently associated with atherosclerosis and plaque (p < or = 0.04).
      Radiographic scores and polymorphonuclear cell counts were also strongly
      associated with plaque (p < or = 0.008). Uric acid concentrations were associated
      with atherosclerosis, and hypothyroidism was associated with plaque, both with
      borderline significance (p = 0.078 and 0.052, respectively). In CART analysis,
      age, polymorphonuclear cell counts, and joint space narrowing in the hands were
      considered to be the most important determinants of plaque, and 62% of patients
      could be classified correctly after cross-validation. Factor analysis (varimax
      rotation) revealed that age and uric acid levels were related to low glomerular
      filtration rates, polymorphonuclear cell counts to disease activity, and
      radiographic scores to disease duration, and hypertension was associated with
      high cholesterol levels. The 10-year risk for a coronary event estimated using
      the Framingham risk equation (calculated from traditional risk factors) was only
      7% in patients with plaque. CONCLUSION: Atherosclerosis in RA is associated with
      the traditional CV risk factors age and hypertension, as well as nontraditional
      risk factors comprising current inflammation as reflected by polymorphonuclear
      cell counts, cumulative inflammation as disclosed by radiographic scores, and, to
      a lesser extent, with uric acid levels and hypothyroidism. Multiple risk factor
      assessment equations that are based on traditional risk factors only are likely
      to be insufficient to capture CV risk extent in RA.

PMID- 15742435
TI  - Valuing a hypothetical cure for rheumatoid arthritis using the contingent
      valuation methodology: the patient perspective.
AB  - OBJECTIVE: A willingness-to-pay (WTP) survey measures the value of a given
      intervention in money terms. We examined the WTP of Canadian patients with
      rheumatoid arthritis (RA) for a hypothetical cure for RA under private and public
      scenarios. The validity of the survey was explored by studying the association
      between WTP and variables thought to be associated with WTP and randomly-varied
      variables of the survey materials. METHODS: A telephone survey was carried out in
      a sample of 121 patients with RA from 5 rheumatologists affiliated with the
      McGill University Health Centre. In advance, patients had been sent a 4-page
      brochure providing a comprehensive description of the disease (including photos
      or no photos). The hypothetical cure for RA was presented through 2 scenarios: a
      private insurance implying an annual premium and a public coverage requiring
      additional income taxes. The survey included questions related to their WTP,
      socioeconomic status (ability to pay), general health, opinion about the
      performance of the healthcare system, and their opinion about the difficulty of
      the survey. For elicitation of WTP, patients were randomized to one of 3 payment
      cards. Mailed questionnaires concerning RA health status were also completed. A
      series of univariate comparisons and multivariate ordered logit regressions were
      carried out to examine the association of WTP and patient and study variables.
      RESULTS: Patients were willing to pay annually significantly more for the private
      program (mean 1190 Canadian dollars) than for the public program (mean 502
      Canadian dollars). Annual WTP was associated with age, household income, site of
      care (private program), private health insurance, opinion about the performance
      of the public healthcare system (public program), and presence of brochure
      photos. The payment card did not affect WTP for either program. CONCLUSION: The
      WTP survey was well understood and accepted by the patients with RA. Although
      measures of RA-specific health status (e.g., Health Assessment Questionnaire)
      were not found to be associated with WTP, many variables thought to be associated
      with WTP were found to be related in the expected directions. Since WTP for the
      private program was higher than that for the public program, our study design did
      not fully capture altruistic valuations of RA patients. Thus, our estimates
      represent a lower bound on patients' WTP for an RA cure.

PMID- 15742436
TI  - Studies of serum C-reactive protein in systemic lupus erythematosus.
AB  - OBJECTIVE: To examine the relationship of serum C-reactive protein (CRP) levels
      to other indicators of disease activity during the course of systemic lupus
      erythematosus (SLE). METHODS: In 124 patients serum CRP was measured
      retrospectively by ELISA and in some instances by radial immunodiffusion. Serum
      CRP levels were compared to laboratory, clinical, and radiographic assessments of
      disease activity. In many patients, serial CRP levels were measured over months
      or years to determine whether elevations of serum CRP reflected apparent changes
      in other disease activity variables. CRP was also measured in lyophilized
      aliquots of 24 h urine samples from SLE patients and controls with other renal
      disorders. Parallel determinations of interleukin 6 (IL-6) were made by ELISA in
      healthy controls and SLE patients. RESULTS: Of the 124 SLE patients studied, most
      showed elevations in serum CRP levels in the course of their disease. No inverse
      or direct correlation was noted between serum CRP and levels of nucleosome
      antigen or serum IgM or IgG anti-DNA antibody. In patients with renal involvement
      and proteinuria, CRP was often detected in 24-h urine samples. A strong
      correlation (p < 0.001) was noted between CRP and IL-6 levels in healthy
      subjects, but no correlation was recorded between serum CRP and IL-6 in SLE.
      CONCLUSION: Contrary to previous reports, most patients with SLE in our study
      showed elevations of serum CRP during the course of their illness, and extremely
      high serum CRP was recorded in some patients. CRP was also found in concentrated
      urine samples from patients with renal involvement and often paralleled elevated
      serum levels. In patients, no correlation was seen between CRP serum levels and
      serum IL-6, whereas a strong correlation between CRP level and IL-6 was recorded
      in healthy subjects.

PMID- 15742437
TI  - Inflammation in patients with lupus anticoagulant and implications for
      thrombosis.
AB  - OBJECTIVE: The underlying mechanism of the prothrombotic state associated with
      the lupus anticoagulant (LAC) has not been fully elucidated. Evidence suggests
      involvement of inflammation in arterial and venous thrombosis, and it may be
      hypothesized that subclinical inflammation aggravates the tendency to thrombosis
      in patients with LAC. METHODS: Levels of high sensitivity C-reactive protein (hs
      CRP), fibrinogen, and factor VIII (VIII) were measured in 38 patients with LAC
      and a history of thrombosis, 27 with LAC and no history of thrombosis, and 33
      healthy controls. RESULTS: Hs-CRP, fibrinogen, and factor VIII levels were
      significantly higher in patients with LAC with thrombosis (hs-CRP median = 0.3
      mg/dl, interquartile range, IQR, 0.11-0.62, p < 0.001 vs controls; fibrinogen
      mean = 395 +/- 90 SD mg/dl, p < 0.001; factor VIII mean = 181 +/- 50%, p = 0.005)
      as well as in those without thrombosis (median = 0.21, IQR 0.10-0.12, p < 0.001;
      mean = 378 +/- 91, p = 0.003; mean = 179 +/- 39, p = 0.015) compared to controls
      (median = 0.07, IQR 0.03-0.12; mean = 308 +/- 48; mean = 137 +/- 39). After
      adjustment for age, body mass index, smoking status, and blood group (only for
      factor VIII) the differences between LAC groups and controls remained
      significant, except for the comparison of fibrinogen between patients without
      thrombosis and controls. The association between LAC and markers of inflammation
      was confirmed using linear regression analysis. Markers of systemic inflammation
      did not differentiate between LAC patients with and without thrombosis (p = 0.829
      for hs-CRP, p = 0.649 for fibrinogen, p = 0.996 for factor VIII). CONCLUSION: Our
      results show that LAC is associated with an inflammatory state. However, there
      was no evidence for an association between inflammatory markers and
      thromboembolism in patients with LAC.

PMID- 15742438
TI  - Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune
      arthritis models.
AB  - OBJECTIVE: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally
      bioavailable molecule known to suppress in vitro the production of tumor necrosis
      factor-alpha (TNF-alpha). We evaluated its therapeutic potential and
      antiinflammatory effects in 3 murine models of adjuvant induced arthritis (AIA).
      METHODS: The antiinflammatory effect of CF101 was examined in rat AIA, in mouse
      collagen induced arthritis, and in tropomyosin induced arthritis. The clinical
      effect of another A3AR agonist, Cl-IB-MECA, was examined in rat AIA. The effect
      of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily on
      arthritis severity was assessed clinically and histologically. The effect of
      CF101 on the protein expression level of TNF-alpha in the synovial tissue,
      draining lymph nodes, and spleen cells was determined by Western blot. RESULTS:
      CF101 and Cl-IB-MECA markedly ameliorated the clinical and histological features
      of arthritis in the 3 models when administered orally at a low dose of 10 mg/kg
      body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of
      either CF101 or Cl-IB-MECA had better antiinflammatory effect than the higher 100
      mg/kg dose. Decreased expression of TNF-alpha was noted in protein extracts of
      synovia, draining lymph nodes, and spleen tissues. CONCLUSION: The results
      provide evidence that A3AR agonists exert significant antirheumatic effects in
      different autoimmune arthritis models by suppression of TNF-alpha production. The
      beneficial activity of the drugs at the low dose demonstrates that the effect is
      A3AR mediated.

PMID- 15742439
TI  - The cytoplasmic dot staining pattern is detected in a subgroup of patients with
      primary biliary cirrhosis.
AB  - OBJECTIVE: To determine the clinical significance of the cytoplasmic dot anti
      "nuclear" antibody (ANA) staining pattern. METHODS: We describe a patient with
      fatigue, arthralgias, elevated serum transaminase, and antibodies staining 5-20
      cytoplasmic dots in HEp-2 cells. A liver biopsy revealed the presence of Stage
      III primary biliary cirrhosis (PBC). Using 2-color immunofluorescence, we
      determined the relationship between the cytoplasmic dot staining pattern and that
      produced by antibodies directed against the GW182 component of mRNA processing
      bodies. To determine the prevalence of the cytoplasmic dot staining pattern in
      patients with PBC, sera from 493 patients were tested for antibodies producing
      this staining pattern. RESULTS: Antibodies in our patient's serum colocalized
      with anti-GW182 antibodies in cytoplasmic dots, but did not react with
      recombinant GW182, suggesting that they were directed against an additional
      component(s) of these structures. The cytoplasmic dot staining pattern was
      observed in 21 of 493 (4.3%) patients with PBC. In comparison, this staining
      pattern was not produced by serum from 248 patients with other autoimmune
      diseases. CONCLUSION: A subset of patients with PBC have autoantibodies that
      produce the cytoplasmic dot staining pattern. These antibodies react with one or
      more as yet unidentified components of the mRNA processing body. Appreciation of
      the clinical significance of the cytoplasmic dot staining pattern may assist in
      appropriate diagnosis and treatment of patients with PBC.

PMID- 15742440
TI  - Central nervous system involvement in hepatitis C virus cryoglobulinemia
      vasculitis: a multicenter case-control study using magnetic resonance imaging and
      neuropsychological tests.
AB  - OBJECTIVE: Involvement of the central nervous system (CNS) in patients with
      hepatitis C virus (HCV) mixed cryoglobulinemia (MC) is rare. The mechanism by
      which brain lesions are produced is unclear. We investigated these phenomena by
      clinical evaluation (neuropsychological tests) and cerebral magnetic resonance
      imaging (MRI) studies in patients with HCV-MC vasculitis. METHODS: This
      prospective study included 40 patients with MC vasculitis and chronic active HCV
      infection (HCV RNA+), 11 HCV controls without MC, and 36 healthy controls,
      matched for sex and age. A battery of 10 standardized neuropsychological tests
      was administered by one experienced neuropsychiatrist. All patients underwent
      cerebral MRI investigation. RESULTS: Twenty-four of the 27 (89%) evaluated
      patients with HCV-MC had a deficiency in one or more of the 10 cognitive domains
      examined. The most commonly involved domains were those of attention (70%),
      executive functions (44%), visual construction (37%), and visual spatial
      functions (33%). The number of impaired cognitive functions was significantly
      higher in patients with MC vasculitis than in HCV controls (2.18 +/- 1.84 vs 0.87
      +/- 3.1; p < 0.05). MRI analysis showed that HCV-MC patients had a higher mean
      number of total (7.03 +/- 9.9 vs 0.90 +/- 1.81 and 2.03 +/- 3.1; p < 0.05) and
      periventricular (2.4 +/- 3.0 vs 0.38 +/- 0.5 and 0.8 +/- 1.4; p < 0.05) white
      matter high intensity signals than HCV controls and healthy controls,
      respectively. CONCLUSION: The high frequency of impaired cognitive function and
      the extent of MRI brain abnormalities in patients with HCV-associated mixed
      cryoglobulinemia vasculitis strongly suggest specific inflammatory involvement of
      the CNS.

PMID- 15742441
TI  - Absence of cyclic citrullinated peptide antibody in nonarthritic patients with
      chronic hepatitis C infection.
AB  - OBJECTIVE: The increased prevalence of rheumatoid factor (RF) in patients with
      chronic hepatitis C virus (HCV) infection markedly diminishes the diagnostic
      specificity of serum rheumatoid factor (RF) for rheumatoid arthritis (RA) in
      patients with HCV. Cyclic citrullinated peptide (CCP) antibody, a highly specific
      biomarker for RA in the general population, may have better diagnostic utility
      for RA in the HCV population. To investigate if CCP antibody retains its
      specificity for RA in HCV infection, we determined the prevalence of CCP
      antibodies and examined the relationship between RF production and CCP antibody
      levels in a population of nonarthritic patients with chronic HCV infection.
      METHODS: CCP antibody and IgM, IgG, and IgA RF isotypes were determined by ELISA
      in serum from nonarthritic patients with chronic HCV infection. RESULTS: In a
      series of 50 HCV patients, IgG-RF, IgM-RF, and IgA-RF were detectable in 52%,
      26%, and 14%, respectively, with a total seropositivity rate of 54%. Marginally
      elevated CCP antibody was detected in a single patient (2%). By regression
      analysis, serum levels of CCP antibodies did not correlate with RF levels.
      CONCLUSION: In contrast to RF, CCP antibody is not increased in HCV infection.
      CCP antibody may have improved utility for the diagnosis of RA in this patient
      population.

PMID- 15742442
TI  - Patients with systemic sclerosis have unique and persistent alterations in
      gastric myoelectrical activity with acupressure to Neiguan point PC6.
AB  - OBJECTIVE: To assess the effect of acupressure on gastric myoelectrical activity
      (GMA) in patients with systemic sclerosis (SSc) and its possible influence on SSc
      associated gastrointestinal (GI) dysmotility disorders. METHODS: Acupressure to
      Neiguan point PC6 (GI, antiemetic point) was applied while SSc patients and
      healthy control subjects were monitored by 4-channel surface electrogastrography
      (EGG) during 30-minute baseline, acupressure, and recovery intervals. Frequency
      of GI symptoms and modified Rodnan skin scores (mRSS) of SSc patients were
      recorded. Acupressure to PC10 (non-GI, sham) was also performed on SSc patients
      to assess the validity of PC6 as a modulator of GI gastric rhythms. RESULTS: In
      the SSc patients, PC6 acupressure resulted in significant, persistent percentage
      mean normal wave decreases with concomitant percentage mean bradygastria and
      tachygastria increases during the recovery interval. Increases in percentage mean
      coupling seen in controls were blunted in SSc patients. In SSc patients, PC6
      acupressure resulted in significant percentage normal wave and percentage
      bradygastria changes in the recovery interval that were not obtained with PC10
      acupressure. In SSc patients, mRSS were significantly correlated to baseline GMA
      percentage mean normal waves and bradygastria and frequency of abdominal
      bloating. The frequency of symptoms for heartburn were significantly correlated
      with changes in GMA (deltaGMA, baseline vs recovery). CONCLUSION: In SSc
      patients, PC6 acupressure revealed significant, persistent, and possibly unique
      alterations in GMA during the recovery interval. deltaGMA was significantly
      correlated with the frequency of heartburn symptoms. Further studies will assess
      if acupressure to PC6 can provide a therapeutic or prognostic utility with GMA or
      GI symptoms in SSc patients.

PMID- 15742443
TI  - Ischemic heart disease in patients from Northwest Spain with biopsy proven giant
      cell arteritis. A population based study.
AB  - OBJECTIVE: To assess the incidence, mortality, and predictors of ischemic heart
      disease (IHD) in patients from the Lugo region of Northwest Spain with biopsy
      proven giant cell arteritis (GCA). METHODS: Retrospective study of patients with
      biopsy-proven GCA diagnosed from 1981 to 2001 at the single hospital for a
      population of 250,000 people. A survival analysis was performed. Hazard ratios
      and standardized mortality ratio (SMR) as well as predictors of IHD in patients
      with biopsy-proven GCA were also assessed. RESULTS: Nineteen (9%) of the 210
      patients with biopsy-proven GCA diagnosed during the period of study had IHD. The
      incidence of IHD in patients with GCA was 12.6/1000 person-years at risk (95% CI
      6.9-21.0). During the study period 1981-2000 the population aged > or = 50 years
      in Lugo was roughly 100,000, and the mortality rate due to IHD in patients with
      GCA for that population was 8/100,000. The SMR in patients with GCA due to IHD
      was 1.62 (95% CI 0.70-3.20). Mortality in patients with GCA who had IHD was
      higher than in those patients without IHD (age and sex adjusted hazard ratio
      2.81, 95% CI 1.51-5.21; p = 0.001). Age (hazard ratio 1.15), hypertension (hazard
      ratio 2.51), and abnormal temporal artery on physical examination (hazard ratio
      0.36) at the time of diagnosis of GCA were the best predictors of IHD over the
      followup period in patients with biopsy-proven GCA. CONCLUSION: Our observations
      suggest that mortality due to IHD in patients from Lugo with GCA is not much
      higher than that reported in the Spanish population aged 50 years and older.
      However, mortality in patients with GCA with IHD is higher than in GCA patients
      without IHD.

PMID- 15742444
TI  - MCP-1 gene haplotype association in biopsy proven giant cell arteritis.
AB  - OBJECTIVE: Giant cell arteritis (GCA) is the most frequent vasculitis in European
      and North American countries. Increased expression of monocyte chemoattractant
      protein 1 (MCP-1) has been observed within the inflammatory infiltrates of blood
      vessels and serum of patients with GCA and in other autoimmune and inflammatory
      conditions. MCP-1 gene polymorphisms have been reported to contribute to
      susceptibility to several immune and inflammatory conditions. To investigate the
      clinical implication of MCP-1 polymorphisms in GCA, we examined the association
      of 3 single nucleotide polymorphisms (SNP) in a series of patients with GCA from
      Northwest Spain. METHODS: Seventy-nine patients with biopsy proven GCA and 99
      ethnically matched controls were studied. Patients and controls were genotyped
      for MCP-1 polymorphisms. SNP included in this study (rs2857657, rs4586, rs139000)
      were located in intron 1(G/C), exon 2(T/C), and 3'UTR(C/T) region of MCP-1 gene.
      RESULTS: The distribution of the alleles and genotypes for each MCP-1
      polymorphism showed no significant differences between GCA patients and controls.
      When we compared the overall distribution of haplotype frequencies between GCA
      cases and controls a significant difference was observed (p = 0.005, by chi
      square test from 4 2 contingency table). In addition, haplotype C-C was
      significantly increased in GCA patients compared with controls (p = 0.03, OR
      2.09, 95% CI 1.09-4.02). Similarly, haplotype T-T was overrepresented in GCA
      patients (p = 0.005). CONCLUSION: Significant differences in haplotype
      frequencies between GCA patients and controls may indicate a role for MCP-1 gene
      in susceptibility to GCA.

PMID- 15742445
TI  - Antibodies to cyclic citrullinated peptides in psoriatic arthritis.
AB  - OBJECTIVE: To determine the presence and clinical significance of antibodies to
      cyclic citrullinated peptides (anti-CCP) in psoriatic arthritis (PsA). METHODS:
      We performed a cross-sectional study on 102 outpatients (56 men) with PsA
      consecutively recruited from a tertiary referral center. Median disease duration
      was 36 months (interquartile range 21-81). All patients were investigated for
      peripheral joint and axial involvement, enthesitis, and dactylitis. Laboratory
      investigations included anti-CCP, assessed by enzyme-linked immunosorbent assay
      and IgM rheumatoid factor (RF). Plain radiographs of pelvis, wrists, hands, and
      feet were performed in all cases. RESULTS: Anti-CCP were detected in 16/102
      patients, 8/68 with symmetric polyarthritis, 1/8 with asymmetric polyarthritis,
      2/20 with mono-oligoarthritis, 1/2 with mutilating arthritis, and 0/4 with
      exclusive axial or distal interphalangeal (DIP) involvement. The male:female
      ratio as well as frequency of dactylitis, enthesitis, and nonexclusive axial or
      DIP joint involvement were similar in the anti-CCP positive and negative groups.
      Anti-CCP positive patients were more frequently treated with disease modifying
      antirheumatic drugs and showed higher number of involved joints, and higher
      frequency of erosive arthritis and positive RF. Using multiple logistic
      regression, anti-CCP (but not RF) were significantly associated with erosive
      arthritis (odds ratio 9.8; 95% confidence interval 1.87-51.8) and > or = 10
      involved joints (17.99; 3.6-89.2). CONCLUSION: Anti-CCP can be found in a small
      but significant proportion of patients with a clinical picture of PsA and are
      associated with erosive arthritis and multiple joint involvement.

PMID- 15742446
TI  - Impact of functional impairment in ankylosing spondylitis: impairment, activity
      limitation, and participation restrictions.
AB  - OBJECTIVE: To describe difficulties in everyday activities related to impaired
      function in patients with ankylosing spondylitis (AS), and to examine possible
      sex differences in the impact of the disease. In addition, to examine the
      relationships between measures of personal characteristics, impairment, and
      activity/participation levels within the framework of the International
      Classification of Functioning (ICF). METHODS: A total of 152 patients with AS
      took part in a clinical examination including anthropometric measures, blood
      samples, and self-reported disease related measures. The Canadian Occupational
      Performance Measure (COPM) interviews were performed to describe and measure
      activity limitations and participation restrictions perceived by the patient
      during the last year. The study variables were categorized and analyzed according
      to the levels of the ICF model using bivariate and multivariate statistical
      approaches. RESULTS: The mean age of patients was 47 (SD 13) years, 58% were men,
      and the mean disease duration was 15 (SD 12) years. The problems most frequently
      reported in COPM interviews were "interrupted sleeping," "turn head when
      driving," "carry groceries," and ""having energy for social activities." Women
      reported higher level of disease activity and more physical limitations than men.
      Disease activity and reduced mobility (impairment variables) seemed to result in
      more activity/participation restrictions in female than in male patients. The
      impairment variables explained only one-third of the activity and participation
      restrictions perceived by patients. CONCLUSION: Activity limitations and
      participation restrictions reported by patients were only partly explained by the
      impairment variables. Further research should identify social, structural, and
      attitudinal barriers influencing activity and participation in patients with AS.

PMID- 15742447
TI  - Reactive joint symptoms following an outbreak of Salmonella typhimurium phage
      type 135a.
AB  - OBJECTIVE: To quantify the incidence and clinical features of reactive arthritis
      (ReA) developing in a cohort exposed to an outbreak of Salmonella typhimurium
      phage type 135a, and factors affecting host susceptibility to ReA. METHODS: A
      screening questionnaire was mailed to 493 patients with confirmed Salmonella
      infection. Musculoskeletal symptoms and extraarticular manifestations of ReA were
      quantified. Positive responders with joint pain were invited to participate
      further, with a detailed history, examination, and investigations including HLA
      B27 status. RESULTS: A total of 261/461 (57%) subjects responded to the
      questionnaire, with 23/54 adults (43%) and 41/207 children (20%) reporting joint
      symptoms. Although joint pains were less common in children compared with adults,
      those children affected usually had eye (34%) or mucocutaneous (37%) symptoms.
      The incidence of ReA was 14.6%, with adults more frequently affected (24%) than
      children (12%). This may be an underestimate given the large proportion of
      children involved. Associated clinical features were similar to previous studies,
      with the distribution of arthritis affecting the lower limbs predominantly in an
      oligoarticular pattern, as were the extraarticular manifestations and
      enthesopathy. We found 17% of subjects were HLA-B27 positive, and 55% were still
      symptomatic after 6 months. CONCLUSION: In an Australian cohort study of a S.
      typhimurium phage type 135a outbreak, joint symptoms were common, affecting 25%
      of subjects. The incidence of ReA of 14.6% and the clinical features were
      comparable to previous studies. There was a small effect of HLA-B27 status on the
      development of ReA.

PMID- 15742448
TI  - Epidemiological differences between back pain of sudden and gradual onset.
AB  - OBJECTIVE: To explore possible differences in risk factors for low back pain
      according to its speed of onset. METHODS: We analyzed longitudinal data from 1366
      hospital nurses in England who initially had been free from low back pain for at
      least one month. Risk factors were ascertained from a self-administered baseline
      questionnaire, and outcomes from serial followup questionnaires. Hazard ratios
      (HR) for developing a first new episode of low back pain during followup were
      derived by Cox regression. RESULTS: Low back pain with gradual onset was
      significantly associated with psychological symptoms measured at baseline [HR 1.7
      (95% CI 1.2, 2.4) and higher], but no such association was seen for sudden pain.
      Low back pain with sudden onset while at work was associated with exposure to
      specific patient-handling tasks [HR 1.8 (95% CI 1.1, 3.0) to 2.8 (95% CI 1.4,
      5.5)]. However, symptoms that came on suddenly elsewhere were not related to
      occupational activity, and low back pain of gradual onset showed little relation
      to patient-handling. CONCLUSION: These findings suggest that a useful distinction
      can be made according to the speed and circumstances of onset of low back pain.
      If confirmed, they have important implications for the evaluation of ergonomic
      interventions aimed at reducing back pain.

PMID- 15742449
TI  - Patient preference in a crossover clinical trial of patients with osteoarthritis
      of the knee or hip: face validity of self-report questionnaire ratings.
AB  - OBJECTIVE: To analyze correlational validity of self-report responses regarding
      patient preference between 2 drugs at the conclusion of a crossover double-blind
      clinical trial in patients with osteoarthritis (OA) of the knee or hip. METHODS:
      Patients were randomized to 6 weeks' treatment of diclofenac/misoprostol or
      acetaminophen, followed by crossover to 6 weeks of the other drug. Patient
      preference was queried at the final visit: "Please compare control of your
      arthritis during the first and second periods as 'much better' or 'better' in the
      first period, 'no different' or 'better' or 'much better' in the second period."
      Patient preference ratings were evaluated in comparisons with 4 independent self
      report measures within each treatment period: (1) change in Western Ontario
      McMaster (WOMAC) questionnaire scores; (2) change in pain visual analog scale
      (VAS) on a multidimensional Health Assessment Questionnaire (MDHAQ); (3) patient
      ratings of drug efficacy; and (4) patient report of change in arthritis status,
      as well as investigator ratings of the more efficacious drug. RESULTS: Among 173
      patients, diclofenac/misoprostol was rated as "much better" by 54 and "better" by
      45, acetaminophen was rated as "better" by 18 and "much better" by 17, and "no
      difference" by 39 patients. Spearman rank correlations for patient preferences
      were significant for changes in WOMAC scores, pain VAS, and independent patient
      ratings of drug efficacy and changes in arthritis status within each treatment
      period, as well as with physician ratings of the more efficacious drug (p <
      0.001). CONCLUSION: Significant correlational validity is documented for patient
      self-report of preferences between 2 drugs compared to independent measures
      within each treatment period in this crossover clinical trial in patients with OA
      of the knee or hip.

PMID- 15742450
TI  - What WOMAC pain score should make a patient eligible for a trial in knee
      osteoarthritis?
AB  - OBJECTIVE: To evaluate different Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) pain thresholds as eligibility criteria for a knee
      osteoarthritis (OA) trial and their effect on number of subjects recruited.
      METHODS: We screened subjects with knee pain using the Likert version of the
      WOMAC and scored all subjects based on the severity of pain with each of the 5
      WOMAC activities. For each of 4 alternative definitions of eligibility, we tested
      how many subjects would be eligible for a trial. RESULTS: Two hundred thirty-four
      subjects with chronic knee pain completed the WOMAC pain survey. If we required a
      score of > or = 4 and at least 2 activities with at least moderate pain, we found
      128 of these subjects were eligible. If we required only one activity with
      moderate pain, the number increased to 139 (by 9%), and further to 161 (by 26%)
      if we required the same overall WOMAC score but no activity with at least
      moderate pain. The most common activity causing moderate or greater pain was
      going up or down stairs. CONCLUSION: The number of subjects recruitable for an OA
      trial depends on the WOMAC pain threshold required. Raising the threshold will
      lower the number of subjects modestly, but include more persons with moderate to
      severe pain. Lowering it may include many with only mild pain with activity.

PMID- 15742451
TI  - Self-management in osteoarthritis of hip or knee: a randomized clinical trial in
      a primary healthcare setting.
AB  - OBJECTIVE: To assess in a primary healthcare setting the efficacy of a self
      management program in middle-aged patients with osteoarthritis (OA). METHODS:
      This was a 2-group randomized controlled trial, with 273 patients aged 40 to 60
      years with OA of the hip(s) and/or knee(s). The experimental intervention was
      compared with care-as-usual. Treatments and followup measurements were performed
      in a general healthcare setting by general practitioners. Duration of followup
      was 21 months after start of the intervention. Instruction in self-management
      techniques was given by physiotherapists. The main outcome measures were pain
      severity in hips and knees, other significant complaints, and functional
      limitations. RESULTS: To begin, 297 patients were randomized: 149 as self
      management and 148 controls; before the intervention 24 withdrew for practical
      reasons (17 self-management, 7 controls). At 3-month followup the intervention
      group was significantly improved on a visual analog scale (VAS) for knee pain
      (score 0.67; SD 2.10) and the WOMAC (score 2.46; SD 9.49), while the control
      group showed stable VAS knee pain (0.01; SD 2.00) and deterioration on WOMAC (
      0.53; SD 9.47). At 21-month followup the differences between the groups increased
      in favor of the intervention group (VAS pain knee: p values from 0.023 at 3 mo to
      0.004 at 21 mo; WOMAC: p values from 0.030 to 0.022). CONCLUSION: The self
      management program positively influenced knee pain and self-reported functional
      level in this sample of patients with OA. Differences between the study groups
      increased during followup in favor of the intervention group.

PMID- 15742452
TI  - Fracture prevalence and treatment with bone-sparing agents: are there urban-rural
      differences? A population based study in Ontario, Canada.
AB  - OBJECTIVE: To estimate the prevalence of self-reported osteoporotic fractures and
      use of bone-sparing agents, and to examine if region of residence is associated
      with fracture or treatment prevalence. METHODS: A census of persons aged > or =
      55 years residing in 2 regions of Ontario, Canada (East York, a region within
      Toronto, and Oxford County), was completed between 1995 and 1998. Region was
      coded by record linkage of residential postal codes to 1996 Canadian Census data
      into 4 groups: East York (urban core), and Oxford County subdivided into: urban
      core, small urban, and rural. Respondents were excluded if they resided outside
      the regions of interest or were missing fracture data (5%). RESULTS: A total of
      26,839 persons (15,541 women) were studied. Nearly 3 times as many women as men
      reported having had an osteoporotic fracture (14% vs 5%), with 31% and 8%,
      respectively, taking bone-sparing agents. Controlling for age, a diagnosis of
      osteoporosis, number of osteoporotic fractures, and height loss, women residing
      in East York were more likely (OR 1.2, 95% CI 1.0-1.4) to be taking a bone
      sparing agent other than estrogen, but less likely to be taking estrogen (OR 0.8,
      95% CI 0.7-0.9) compared to those living in rural areas. No regional differences
      were observed in fracture prevalence, treatment among those with an osteoporotic
      fracture, or use of a bone-sparing agent among men. CONCLUSION: Further research
      into regional differences in osteoporosis screening, treatment, and fractures is
      warranted. This should examine the appropriateness of possible differences, and
      separate physician practice patterns from patient characteristics, such as
      willingness to begin treatment with bone-sparing agents.

PMID- 15742453
TI  - Evaluation of revised International League of Associations for Rheumatology
      classification criteria for juvenile idiopathic arthritis in Spanish children
      (Edmonton 2001).
AB  - OBJECTIVE: To evaluate the revised (Edmonton 2001) International League of
      Associations for Rheumatology (ILAR) classification criteria for Juvenile
      Idiopathic Arthritis (JIA) in a cohort of Spanish children. METHODS: One hundred
      twenty-five patients with chronic arthritis categorized according to traditional
      criteria and to the first revision of ILAR JIA criteria (Durban 1997) were
      reclassified according to the second JIA criteria revision (Edmonton 2001).
      RESULTS: Edmonton criteria allocated 92% of the patients classified by
      traditional criteria in their corresponding ILAR categories. Most patients with
      systemic (94%), pauciarticular (91%) and polyarticular (88%) juvenile chronic
      arthritis as well as those with juvenile spondyloarthropathy (94%) were
      reclassified in the corresponding ILAR categories. Two children with probable
      psoriatic arthritis (PsA) were reclassified in the rheumatoid factor-negative (RF
      ) polyarthritis category, whereas only one of 2 children with definite PsA could
      be allocated to the ILAR PsA class. Ten patients (8%) constituted the
      undifferentiated arthritis group, 8 because of psoriasis in a first-degree
      relative, one because of the presence of RF in a girl with oligoarthritis, and
      another because of psoriasis in a boy who was HLA-B27-positive. In comparison
      with the Durban JIA criteria the Edmonton revision decreased the number of
      patients whose arthritis fulfilled criteria in no category or in 2 or more
      categories (from 19 to 10), and delineated better the population included in the
      RF- polyarthritis category. CONCLUSION: The Edmonton criteria made the ILAR
      classification more transparent and easy to apply. Family history of psoriasis
      was responsible for most allocations to the undifferentiated arthritis category
      (8/10).

PMID- 15742454
TI  - Two cases of antinuclear antibody negative lupus showing increased proportion of
      B cells lacking RP105.
AB  - B cells lacking RP105 molecule, a member of the Toll-like receptor family, were
      increased in the peripheral blood of 2 patients with antinuclear antibody (ANA)
      negative systemic lupus erythematosus (SLE). The increased proportion of RP105
      lacking B cells was associated with disease activity in patients with ANA
      negative SLE. When there are no significant serological markers for SLE, analysis
      of expression of RP105 may be helpful in evaluation of activity in ANA-negative
      SLE. We describe a new approach, using phenotyping of B cells, to evaluate
      activity of ANA-negative SLE.

PMID- 15742455
TI  - Multicentric reticulohistiocytosis responding to tumor necrosis factor-alpha
      inhibition in a renal transplant patient.
AB  - Multicentric reticulohistiocytosis (MRH) is a rare systemic disease that
      characteristically produces severe erosive arthritis of the distal and proximal
      interphalangeal joints along with cutaneous nodules over the upper extremities
      and face, but it can be found in other organs. There is no known etiology, and it
      often remits spontaneously within 5-10 years, but can result in severe
      disfigurement. The diagnosis is made when histologic analysis of involved
      synovium or cutaneous nodules reveals characteristic histopathology. We describe
      a case of MRH manifesting as erosive arthritis that developed despite
      immunosuppressive therapy. Based on studies reporting tumor necrosis factor-a
      (TNF-alpha) positive cells within MRH lesions, we began treatment with TNF-alpha
      inhibition. Within 2 months the patient showed dramatic clinical and serologic
      improvement that was maintained until she stopped treatment secondary to an upper
      respiratory tract infection. Once treatment was restarted, the symptoms again
      improved.

PMID- 15742456
TI  - Mechanism of action of tumor necrosis factor antagonists. Proceedings of the
      Canadian expert roundtable meeting, Banff, Canada, November 28-30, 2003.

PMID- 15742457
TI  - Differentiating the efficacy of tumor necrosis factor inhibitors.
AB  - Blockade of tumor necrosis factor (TNF) has emerged as one of the most promising
      therapies in rheumatoid arthritis (RA). Three agents are currently available as
      specific TNF antagonists, etanercept (Enbrel), infliximab (Remicade), and
      adalimumab (Humira). Data from noncomparative trials suggest that all 3 agents
      have comparable therapeutic activity in RA. Etanercept and infliximab have also
      demonstrated beneficial activity in other inflammatory arthritides [i.e.,
      psoriatic arthritis and ankylosing spondylitis (both agents) and juvenile
      rheumatoid arthritis (etanercept only)] and inflammatory diseases (i.e.,
      psoriasis and uveitis). Their effects in granulomatous diseases are more
      variable, with only infliximab demonstrating clear efficacy in the treatment of
      Crohn's disease, sarcoidosis, and Wegener's vasculitis. In this brief review
      current efficacy data are summarized and possible explanations for observed
      clinical differences are explored.

PMID- 15742458
TI  - Safety of biologic therapies--an update.
AB  - Tumor necrosis factor (TNF) antagonists have set a new therapeutic standard for
      rheumatoid arthritis (RA). Agents including infliximab, etanercept, and
      adalimumab have demonstrated substantial improvement in signs and symptoms,
      disability, and quality of life, while significantly inhibiting joint damage in
      early and long-standing RA. Safety issues in concert with efficacy determine
      risk/benefit ratio and hence a position in the therapeutic algorithm. This brief
      review focuses on infection, congestive heart, and malignancy.

PMID- 15742459
TI  - Clinical pharmacokinetics of tumor necrosis factor antagonists.
AB  - Clinical pharmacokinetics of the 3 existing marketed tumor necrosis factor (TNF)
      antagonists, adalimumab (Abbott Laboratories), etanercept (Amgen, Inc.), and
      infliximab (Centocor, Inc.) are reviewed. The relevance and potential clinical
      implications of any differences in their pharmacokinetic properties are outlined.
      The major therapeutic goal when administering TNF antagonists is to eliminate the
      surplus of TNF from the circulation and from sites of inflammation. Within the
      causal chain of events after a drug is administered the exposure (or
      pharmacokinetics) precedes the effect (or pharmacodynamics). The differences in
      the observed concentration-time profiles and the exposure characteristics derived
      from them are induced either by differences of the inherent properties of the
      molecules (such as binding to various receptors, absorption and clearance
      mechanisms and rates, etc.), or by the differences in the dosage and
      administration regimens of the drugs (such as dose magnitude, administration
      frequency, route of administration, etc.). Review of the dose exposure-response
      cascade of the TNF antagonists shows that: (1) their pharmacokinetic properties
      should be interpreted in the context of the "therapeutic window" paradigm; and
      (2) exposure of tissues and fluids is a primary determinant of the drug
      action/adverse action. Therefore, efforts should be made to evaluate the
      pharmacokinetics of the TNF antagonists in such tissues/fluids of interest as the
      inflammation sites (e.g., synovium, gut mucosa, skin lesions) and sites of
      potential adverse effects (e.g., lungs).

PMID- 15742460
TI  - Apoptosis in the regulation of immune responses.
AB  - Apoptosis, or programmed cell death, is an active process required for the
      regulation of immune responses. T cell apoptosis may represent a protective
      mechanism that limits peripheral damage by T cells during immune response. The
      underlying biological processes responsible for morphological aspects of
      apoptosis are becoming better defined. Concepts reviewed here include caspase
      activation, death pathways, and crosstalk between death ligands and their
      receptors.

PMID- 15742461
TI  - Infliximab induced T lymphocyte apoptosis in Crohn's disease.
AB  - Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal
      tract of unknown origin. Therapies include immune modulating agents, biological
      therapies, and surgery. The activity and efficacy of the anti-tumor necrosis
      factor (TNF) therapies infliximab and etanercept have proved to be different:
      infliximab is effective to induce and maintain remission in refractory CD, while
      etanercept is not. This brief review considers the question of whether this
      disparity can be explained by the different structure of the proteins, their
      different binding affinities, or the subsequent effects on T lymphocytes.

PMID- 15742462
TI  - Effects of infliximab treatment on rheumatoid synovial tissue.
AB  - Several studies have shown decreased synovial inflammation after treatment of
      patients with rheumatoid arthritis (RA) with infliximab. Recent data indicate
      that these effects can be detected as soon as 48 hours after first infusion.
      Although there are strong indications that infliximab exerts its effects in
      patients with Crohn's disease by induction of apoptosis in the gut, there are as
      yet no studies that convincingly show the same mechanism of action in RA.
      Conceivably, neutralization of tumor necrosis factor-alpha may be sufficient to
      induce clinical improvement in RA, even without induction of apoptosis at the
      site of inflammation. This hypothesis could explain the observation that both
      infliximab and etanercept are effective in RA, whereas apoptosis induction by
      infliximab might be required in Crohn's disease. Future studies should focus on
      the evaluation of apoptosis within the first 48 hours after initiation of therapy
      in RA to exclude the possibility that the effects occur very early after
      infliximab infusion.

PMID- 15742463
TI  - Why does tumor necrosis factor targeted therapy reactivate tuberculosis?
AB  - Treatment of chronic inflammatory conditions, such as rheumatoid arthritis and
      Crohn's disease, with tumor necrosis factor (TNF) targeted biologics is
      associated with an increased risk of infectious complications, especially
      tuberculosis (TB). Clinical studies have revealed that monoclonal anti-TNF
      antibodies (e.g., infliximab) more frequently reactivate TB than a TNF receptor
      p75 immunoglobulin fusion construct (etanercept). Experimental studies in mice
      have shown TNF to be an essential component of protective granuloma formation.
      Based on these studies and the known pharmacological properties of the 2
      prototype TNF targeted biologic agents, this review discusses 3 hypotheses that
      might explain the unpredicted differential risk of infectious complications:
      differential induction of target cell death, differential TNF receptor signaling,
      and differential net inhibition of TNF bioavailability.

PMID- 15742464
TI  - Differences between anti-tumor necrosis factor-alpha monoclonal antibodies and
      soluble TNF receptors in host defense impairment.
AB  - This review examines the differences in the incidence, spectrum, and mechanisms
      of activation of opportunistic infections, such as Mycobacterium tuberculosis, in
      patients with rheumatic diseases treated with the soluble TNF p75 receptor
      etanercept compared to the 2 anti-TNF-alpha monoclonal antibodies, infliximab and
      adalimumab.

PMID- 15742465
TI  - Expression and transport function of the glutamate transporter EAAC1 in Xenopus
      oocytes is regulated by syntaxin 1A.
AB  - The function of several membrane proteins is regulated by interaction with the
      SNARE protein syntaxin 1A; this includes regulation of GAT1, the transporter for
      the dominating inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here
      we demonstrate that also EAAC1, the transporter for the dominating excitatory
      neurotransmitter, is down-regulated by interaction with syntaxin 1A. This is
      shown by coexpression of EAAC1 and syntaxin 1A in Xenopus oocytes. Total EAAC1
      expression is not significantly affected by the coexpression of syntaxin 1A, but
      more proteins become targeted to the membrane as demonstrated by biotinylation.
      Colocalization by coimmunoprecipitation suggests direct interaction between the
      two proteins. In contrast to the number of transporters, the glutamate transport
      activity becomes reduced, and even stronger inhibition is observed for the EAAC1
      mediated conductance uncoupled from glutamate translocation. We conclude that the
      interaction of syntaxin 1A with EAAC1 particularly disrupts the structure of the
      conductance pathway of EAAC1.

PMID- 15742466
TI  - Novartis award to J. S. Clark and J. P. Clayden.

PMID- 15742467
TI  - Gold liquid crystals displaying luminescence in the mesophase and short F...F
      interactions in the solid state.
AB  - Rodlike gold(I) complexes, [Au(C6F4OCmH2m+1)(C(triple bond)NC6H4C6H4OCnH2n+1)]
      (m=2, n=4, 10; m=6, n=10; m=10, n=6, 10), display interesting features. They are
      liquid crystals and show photoluminescence in the mesophase, as well as in the
      solid state and in solution. The single-crystal, X-ray diffraction structure of
      [Au(C6F4OC2H5)(C(triple bond)NC6H4C6H4OC4H9)] confirms its rodlike structure,
      with a linear coordination around the gold atom, and reveals the absence of any
      Au...Au interactions (such interactions are often present in luminescent gold
      complexes). Well-defined, intermolecular Fortho...Fmeta interactions, with
      remarkably short intermolecular FF distances (2.66 A), are observed; these
      interactions seem to be responsible for the crystal packing, which consists of an
      antiparallel arrangement of molecules. Experiments under different conditions
      support the explanation that the photoluminescence has an intramolecular origin.

PMID- 15742468
TI  - Investigations on the iron-catalyzed asymmetric sulfide oxidation.
AB  - The development of an enantioselective sulfide oxidation involving a chiral iron
      catalyst and aqueous hydrogen peroxide as oxidant is described. In the presence
      of a simple carboxylic acid, or a carboxylate salt, the reaction affords
      sulfoxides with remarkable enantioselectivities (up to 96 % ee) in moderate to
      good yields. The influence of the structure of the additive on the reaction
      outcome is reported. In the sulfoxide-to-sulfone oxidation a kinetic resolution
      (with s = 4.8) occurs, which, however, plays only a negligible role in the
      overall enantioselective process. Furthermore, a positive nonlinear relationship
      between the ee of the product and that of the catalyst has been found. On the
      basis of these observations, a possible catalyst structure is proposed.

PMID- 15742469
TI  - Water-catalyzed dehalogenation reactions of the isomer of CBr4 and its reaction
      products and a comparison to analogous reaction of the isomers of di-and
      trihalomethanes.
AB  - A combined experimental and theoretical study of the UV photolysis of a typical
      tetrahalomethane, CBr4, in water and acetonitrile/water was performed.
      Ultraviolet photolysis of low concentrations of CBr4 in water mostly leads to the
      production of four HBr leaving groups and CO2. Picosecond time-resolved resonance
      Raman (Ps-TR3) experiments and ab initio calculations indicate that water
      catalyzed O-H insertion/HBr elimination of the isomer of CBr4 and subsequent
      reactions of its products lead to the formation of these products. The UV
      photolyses of di-, tri-, and tetrahalomethanes at low concentrations in water
      solvated environments are compared to one another. This comparison enables a
      general reaction scheme to be deduced that can account for the different products
      produced by UV photolysis of low concentrations of di-, tri-, and
      tetrahalomethanes in water. The fate of the (halo)formaldehyde intermediate in
      the chemical reaction mechanism is the key to determining how many strong acid
      leaving groups are produced and which carbon atom final product is likely formed
      by UV photolysis of a polyhalomethane at low concentrations in a water-solvated
      environment.

PMID- 15742470
TI  - Amino acid binding by 2-(guanidiniocarbonyl)pyridines in aqueous solvents: a
      comparative binding study correlating complex stability with stereoelectronic
      factors.
AB  - A series of guanidiniocarbonylpyridine receptors has been synthesized, and these
      compounds bind amino acids (carboxylate forms) in aqueous DMSO with association
      constants ranging from K = 30 to 460 M(-1) as determined by NMR titration
      experiments. The differences in the complex stabilities can be correlated with
      steric and electrostatic effects with the aid of calculated complex structures.
      For example, the electrostatic repulsion between the pyridine nitrogen lone pair
      and the bound carboxylate makes anion binding less efficient than with the
      analogous pyrrole receptors previously introduced by us for carboxylate binding
      in water. Furthermore, steric interactions between the receptor side chain as in
      2 b and the bound substrate also disfavor complexation.

PMID- 15742471
TI  - [Urinary and fecal incontinence in the aged from gynecologic proctologic
      viewpoint].
AB  - Three to four million women suffer from urinary incontinence (UI) in Germany.
      This number will rise further as life expectancy increases, and there is an
      annual incidence of newly occurring UI of about 1%. Two thirds of all women with
      UI suffer additional symptoms of fecal incontinence. The type of incontinence
      present is diagnosed on the basis of patients history, clinical findings, and
      functional testing. The findings should be interpreted in an age-adjusted manner
      to avoid over-rating (e.g. urethral closure pressure at rest=100-age in cm
      H(2)O). The management of elderly patients focuses on conservative approaches
      with bladder and intestinal training as well as dietary measures serving to
      counteract the age-related loss of intellectual abilities. Local estrogen
      application has a positive effect on all forms of incontinence. Surgical
      approaches aim at improving symptoms since forced restoration of incontinence in
      elderly patients frequently induces voiding disorders.

PMID- 15742472
TI  - Health in the Arctic Circle.

PMID- 15742473
TI  - Russia's population crisis.

PMID- 15742474
TI  - Novel c-KIT germline mutation in a family with gastrointestinal stromal tumors
      and cutaneous hyperpigmentation.
AB  - Mutations in the c-KIT gene have been identified in many sporadic and familial
      cases of gastrointestinal stromal tumor (GIST). We report a familial case of GIST
      with cutaneous hyperpigmentation associated with a novel germline mutation in the
      c-KIT gene. Screening for mutations in exon 11 of the c-KIT gene in genomic DNA
      from tumors and peripheral blood of the members of a family with GISTs was
      undertaken by direct genomic sequencing. Tumors from GIST patients were analyzed
      histologically and immunohistochemically. Clinical examination of GIST patients
      was also performed to detect other systemic diseases associated with c-KIT
      mutations. Histological study showed that the tumors were GISTs expressing CD34
      and c-KIT protein. This GIST-hyperpigmentation disease was associated in the
      family with a germline mutation in the c-KIT gene. The mutation is a duplication
      of the sequence CAACTT located in exon 11 of the c-KIT gene, which introduces two
      extra glutamine and leucine residues in the encoding protein between positions
      576 and 577. This Spanish family was affected with GISTs and cutaneous
      hyperpigmentation associated with a novel germline mutation
      Leu576_Pro577insGlnLeu in the juxtamembrane domain of the c-KIT receptor. These
      types of mutation in the c-KIT gene activate the tyrosine kinase activity of the
      c-KIT receptor and induce constitutive signaling leading to GISTs, in some cases
      associated with cutaneous hyperpigmentation.

PMID- 15742475
TI  - Interstitial deletion of the long arm of chromosome 5 in a boy with multiple
      congenital anomalies and mental retardation: Molecular characterization of the
      deleted region to 5q22.3q23.3.
AB  - Interstitial deletions of the middle portion of the long arm of chromosome 5 are
      relatively rare. So far, only 36 cases have been reported. Because of the
      repetitive banding pattern of this region, the extent and localization of the
      deleted segment has not been well characterized in the majority of reported
      cases. This has complicated attempts to establish a definite karyotype-phenotype
      correlation. We report a further case with a de novo interstitial deletion of the
      region 5q?15 to 5q?22 identified by standard karyotype analysis. The proband
      presented with failure to thrive, developmental delay, distinct craniofacial
      dysmorphic features, and associated structural anomalies (amongst them cleft
      palate, iris colobomata, and horseshoe kidney, which have previously been
      reported in 5q deletion cases). In addition, this child had an Arnold-Chiari type
      I malformation that required surgical decompression. FISH studies using BAC
      clones spanning the 5q15 to 5q22 region revealed that these were all present in
      both homologues. Use of more distal clones allowed delineation of the deleted
      region to 5q22.3q23.3 and to narrow down the breakpoints to approximately 200 kb.
      The 14 Mb deleted region contains about 60 genes but, with the possible exception
      of FBN2 and DMXL1, there are no obvious candidate genes for the specific
      components of the phenotype. This case illustrates the discrepancy between
      cytogenetic and molecular techniques in trying to delineate 5q interstitial
      deletions. Molecular studies need to be performed on these patients, to establish
      genotype-phenotype correlation and to understand the role and influence of genes
      in this region.

PMID- 15742476
TI  - Twist is an integrator of SHH, FGF, and BMP signaling.
AB  - Development of vertebrate embryos is regulated by a number of different signaling
      pathways. These pathways are frequently not independent of each other but are
      connected by crosstalk between cells and tissues. Furthermore, different
      signaling pathways have been found to interact at the cellular level. Development
      of cranial and limb structures is an example, in which FGF, BMP, and SHH
      signaling interact. Mutations in the different signaling pathways may therefore
      result in complex but similar phenotypes. This indicates the existence of
      integrator molecules, which depend in their expression or activity on the
      combination of different signaling pathways. Here we show that expression of the
      bHLH transcription factor Twist in the paraxial mesoderm requires an induction
      from the notochord. This induction can only be substituted by a combination of
      FGF and SHH signaling, but not by individual application of FGF8 or SHH alone.
      Furthermore, the expression of Twist can be modified by BMP2 in a complex, age
      dependent manner. We propose that Twist is one of the integrating parts of the
      three signaling pathways and mediates some of the common effects.

PMID- 15742479
TI  - Can a PET scan help diagnose Alzheimer's disease?

PMID- 15742478
TI  - A critical analysis of criticisms of the Oregon Death with Dignity Act.
AB  - This article critically examines the validity of common criticisms of the Oregon
      Death with Dignity Act, primarily through reviewing published research and
      analyses. After summarizing the law and recent developments, 11 areas of concerns
      are examined: (a) the amount of data collected, (b) the availability of the data,
      (c) the reporting process, (d) protection of physicians, (e) terminal illness as
      a requirement, (f) the amount of data on palliative care interventions, (g) data
      on lethal prescriptions, (h) data on psychological/psychiatric evaluations, (i)
      whether the decision to request medication is informed, (j) whether the request
      is voluntary, and (k) financial factors. The authors examine each of these areas
      of concern and find criticisms to be unfounded given the research and analyses
      conducted to date.

PMID- 15742480
TI  - Aortic stenosis: steps toward new treatment.

PMID- 15742481
TI  - Bones are big news.

PMID- 15742482
TI  - Should you join a clinical trial?

PMID- 15742484
TI  - I've booked a cruise, but I'm afraid I might become seasick. Can the acupressure
      wristbands I've seen at the pharmacy help?

PMID- 15742483
TI  - I've read that I should avoid antioxidant supplements. Should I be worried about
      antioxidants in a multivitamin?

PMID- 15742486
TI  - Protecting your income.

PMID- 15742485
TI  - [The anterior parenchymatous approach (Ton That Tung): a reevaluation from the
      viewpoint of modern hepatic surgery].

PMID- 15742487
TI  - Position statement 7: Birth centres.

PMID- 15742488
TI  - IT initiative designed to help doctors improve patient safety and quality of
      care.

PMID- 15742489
TI  - [The "Annales de Chirurgie" at a cross road].

PMID- 15742490
TI  - Medical genetics is playing an important role in the public health care in China.
      Conference Report for the International Conference of Medical Genetics 2004,
      Beijing.

PMID- 15742491
TI  - The imperative to treat: the South African state's constitutional obligations to
      provide antiretroviral medicines.

PMID- 15742492
TI  - Paying research subjects: historical considerations.

PMID- 15742493
TI  - "To become old is to become institutionalized and imprisoned": comparing
      regulatory frameworks for the use of restraints in long-term care facilities.

PMID- 15742494
TI  - Section 7 of the Charter: a constitutional right to health care? Don't hold your
      breath.

PMID- 15742495
TI  - Population genetic studies: is there an emerging legal obligation to share
      benefits?
AB  - It appears that large-scale population genetic studies are the necessary next
      step in genomics research. Such studies promise to provide correlative data to
      permit researchers to understand the etiology of a vast array of complex human
      diseases. Simultaneously, such studies are increasingly seen as yet another
      mechanism for the developed world to benefit at the expense of the developing
      world. In fact, a recent World Health Organization Report suggests that "without
      explicit attention at the international level, the initial technological fruits
      of genomics are likely to consist primarily of therapeutic and diagnostic
      applications for conditions affecting large populations in rich countries."
      (World Health Organization, Genomics and World Health, 2002). In developed and
      developing countries alike, there are concerns that the pharmaceutical industry
      stands to gain at the expense of the population(s) from which population genetic
      data are derived. In light of the current interest concerning ongoing population
      genetic studies and an increasing interest by many countries, Canada included, in
      embarking on large-scale population genetic research, it is appropriate to
      consider the concept of benefit-sharing as a potential mechanism to assuage these
      concerns. It is the author's position that by virtue of common law equitable
      principles and developing norms in international law, including the Human Genome
      Organization Statement on Benefit-Sharing, that there are principled legal and
      ethical reasons to compel the sharing of benefits that accrue from the
      commercialization of the resulting data. Using the United Nations Convention on
      Biological Diversity and the Bonn Guidelines as a model, I suggest that
      appropriate benefit-sharing mechanisms have been considered in the context of non
      human biological materials and that these same mechanisms may be applicable in
      the context of international and intra-national population genetic studies.

PMID- 15742496
TI  - Consistency and privacy: do these legal principles mandate gamete donor
      anonymity?

PMID- 15742497
TI  - It's not (just) about privacy: a new perspective on health databases.

PMID- 15742498
TI  - The Australian policy debate about human embryonic stem cell research.

PMID- 15742499
TI  - Regulating a revolution: the extent of reproductive rights in Canada.

PMID- 15742500
TI  - Persons who fail to disclose their HIV/AIDS status: conclusions reached by an
      expert working group.

PMID- 15742501
TI  - Avian influenza, Vietnam.

PMID- 15742502
TI  - American Association of Feline Practitioners/Academy of Feline Medicine Panel
      Report on Feline Senior Care.

PMID- 15742503
TI  - Immunoaffinity CE for proteomics studies.

PMID- 15742504
TI  - Forensic chemistry education.

PMID- 15742505
TI  - Baby boy on heart pump receives transplant.

PMID- 15742506
TI  - Medical editors likely to call for registration of drug tests at outset.

PMID- 15742507
TI  - On death row, a battle over the fatal cocktail: critics say executions amount to
      torture.

PMID- 15742508
TI  - Biology's new forbidden fruit.

PMID- 15742509
TI  - Patients in test won't get drug, Amgen decides.

PMID- 15742510
TI  - As girls 'vanish,' Chinese city battles tide of abortions.

PMID- 15742512
TI  - Judge delays feeding tube removal.

PMID- 15742511
TI  - Panel to advise tests on babies for 29 diseases.

PMID- 15742513
TI  - Moving stem cells front and center: researcher makes paralyzed rats walk and
      asks, why not people?

PMID- 15742514
TI  - Justices accept case weighing assisted suicide.

PMID- 15742515
TI  - Florida steps back into fight over feeding tube for woman.

PMID- 15742516
TI  - Drug companies cut costs with foreign clinical trials.

PMID- 15742518
TI  - U.S., researchers reach deal in '99 gene therapy case.

PMID- 15742517
TI  - Kansas prosecutor demands files on late-term abortion patients.

PMID- 15742519
TI  - U.S. denies patent for a too-human hybrid: scientist sought legal precedent to
      keep others from profiting from similar "inventions".

PMID- 15742520
TI  - A struggling science experiment: states closely watch California's stem cell
      research initiative.

PMID- 15742521
TI  - Too strict at NIH.

PMID- 15742523
TI  - Diversity at every level.

PMID- 15742522
TI  - NIH clears most researchers in conflict-of-interest probe.

PMID- 15742525
TI  - Clusters-local service providers. The National Programme for IT.

PMID- 15742524
TI  - AIDS vaccine on test in India.

PMID- 15742526
TI  - Dermatology.

PMID- 15742527
TI  - Sacral nerve stimulation for urinary control.

PMID- 15742529
TI  - Once more unto the breach, vis-a-vis the latest approach to management
      strategies.

PMID- 15742530
TI  - On the limitations of specialists.

PMID- 15742528
TI  - Clinical trial budgets.

PMID- 15742532
TI  - Rural population finds itself on receiving end of urban policy again.

PMID- 15742531
TI  - Atypical hematological response to combined calorie restriction and chronic
      hypoxia in Biosphere 2 crew: a possible link to latent features of hibernation
      capacity.
AB  - Eight humans were isolated for 2 years in Biosphere 2, a sealed airtight habitat
      with recycled air, food, water, and wastes. A combination of conditions led to
      selective decline of oxygen (O2) in the internal atmosphere from 21% to 14%,
      inducing symptoms of high-altitude sickness but with little or no compensatory
      increase in red cell production. All crew members exhibited significant decreases
      in both erythrocyte 2,3-bisphosphoglycerate (2,3-BPG) concentrations and P50
      [partial pressure of O2 for 50% hemoglobin (Hb) saturation] values, changes
      opposite those expected in adaptation to high-altitude hypoxia. Lower P50 with
      increased Hb-O2 affinity induced by low 2,3-BPG is a characteristic of
      hibernating species and could be advantageous in O2-impoverished environments.
      The mechanisms underlying these changes in the Biosphere 2 crew remain obscure
      but could be related to low-calorie diet (1750-2100 kcal/day). Because the
      combination of hypoxia and limited caloric intake is also characteristic of
      hibernation, this unusual response may represent a cross-adaptation phenomenon in
      which certain features of hibernation capability are expressed in humans.

PMID- 15742533
TI  - Development of a 1-week cycle menu for an Advanced Life Support System (ALSS)
      utilizing practical biomass production data from the Closed Ecology Experiment
      Facilities (CEEF).
AB  - Productivities of 29 crops in the Closed Ecology Experiment Facilities (CEEF)
      were measured. Rice and soybean showed higher productivities than these given by
      the Advanced Life Support System Modeling and Analysis Project Baseline Values
      and Assumption Document (BVAD), but productivities of some other crops, such as
      potato and sweet potato, were lower. The cultivation data were utilized to
      develop a 1-week cycle menu for Closed Habitation Experiment. The menu met most
      of the nutritional requirements. Necessary cultivation area per crew was
      estimated to be 255 m2. Results from this study can be used to help design the
      future Advanced Life Support System (ALSS) including the CEEF.

PMID- 15742534
TI  - Nanostructured oxide-based selective gas sensor arrays for chemical monitoring
      and medical diagnostics in isolated environments.
AB  - MoO3 and MoO3-WO3-based resistive type sensors/arrays have been used for the
      detection of toxic gaseous compounds important to environmental monitoring and to
      medical diagnostics. The responses of the sensing elements when exposed to 400
      ppm of methanol, 10 ppm of isoprene, and 15 ppm of ammonia at temperatures
      between 400 degrees C and 500 degrees C have been assessed. A correlation was
      made between the crystallography of the nanostructured oxide sensing films and
      their relative gas selectivity to the analytes of interest. Arrays of selective
      sensing elements are proposed as valuable tools for the survival of humans in
      isolated environments and for space exploration.

PMID- 15742535
TI  - On location: South Yorkshire. Steely determination wins stars and cuts inequality
      in Sheffield.

PMID- 15742537
TI  - HR director of the year.

PMID- 15742536
TI  - Online fault adaptive control for efficient resource management in Advanced Life
      Support Systems.
AB  - This article presents the design and implementation of a controller scheme for
      efficient resource management in Advanced Life Support Systems. In the proposed
      approach, a switching hybrid system model is used to represent the dynamics of
      the system components and their interactions. The operational specifications for
      the controller are represented by utility functions, and the corresponding
      resource management problem is formulated as a safety control problem. The
      controller is designed as a limited-horizon online supervisory controller that
      performs a limited forward search on the state-space of the system at each time
      step, and uses the utility functions to decide on the best action. The
      feasibility and accuracy of the online algorithm can be assessed at design time.
      We demonstrate the effectiveness of the scheme by running a set of experiments on
      the Reverse Osmosis (RO) subsystem of the Water Recovery System (WRS).

PMID- 15742538
TI  - Script generation following frontal and parietal lesions.
AB  - The purpose of this investigation was to distinguish putative effects of parietal
      lobe lesions on script generation, in distinction from the better known and
      established effects of frontal lobe lesions. Nine patients, most with excised
      parietal lesions, were compared to nine age, gender and education matched normal
      participants. Eleven patients with excised tumors of the frontal lobe were
      compared to twelve age, gender and education matched normal subjects.
      Participants were requested to generate, out loud, scripts corresponding to
      everyday activities. Half the scripts were relatively more demanding with respect
      to temporal representation (understanding the time line of events) and the other
      half with respect to spatial representation (understanding the layout of the
      actions in space). These two conditions were further broken down into conditions
      of high and low demands on working memory (reciting the scripts backwards versus
      forward). The frontal lobe patients enunciated significantly fewer actions
      overall. They were also significantly more impaired than the normal participants
      on all tasks with high demands on working memory, and more often, high temporal
      demands (sequencing and perseverative errors). The parietal lobe patients had
      significant difficulty in sequencing in all conditions, and manifested no
      perseveration. Though script generation tasks have been primarily associated with
      frontal lobe function until now, consideration should be given to the type of
      activity being scripted as a function of relative demands on spatial or temporal
      representation, as well as working memory, and the contributions of other lobes
      ought to be taken into consideration.

PMID- 15742539
TI  - Age-related impairment in executive functioning: updating, inhibition, shifting,
      and access.
AB  - Miyake, Friedman, Emerson, Witzki, Howerter and Wager (2000) have argued that the
      central executive is fractionated consisting of at least three separable
      component processes: updating, shifting, and inhibition. The Wisconsin Card Sort
      Test, random letter generation, Brooks spatial sequences, reading and computation
      span, word fluency, and a measure of dual task performance were administered to
      95 individuals aged between 20 and 81, average age 41.89. The executive measures
      were factor analyzed, using the oblique rotation method, yielding four factors.
      The factor structure obtained was broadly consistent with Miyake et al's.
      However, an additional factor, the only one not to show a significant performance
      decline with age, was also obtained and was believed to reflect the efficiency of
      access to long-term memory.

PMID- 15742540
TI  - Boston naming test short forms: a comparison of previous forms with new item
      response theory based forms.
AB  - Two new short forms of the Boston Naming Test (BNT) were developed using item
      response theory (IRT) with data from 206 elderly outpatients. We evaluated the
      diagnostic ability of 12 short forms among the full sample and in a sub-sample of
      69 patients diagnosed with mild Alzheimer's disease (AD) either alone or in
      combination with vascular dementia (VD). The full BNT (reliability alpha = .90)
      identified 44% of the AD/VD patients as abnormal on naming. Our 30 item short
      form (alpha = .90) also identified 44% of the AD/VD patients as abnormal, with
      93% agreement with the full BNT on abnormal AD/VD patient classifications. Our 15
      item short form (alpha = .84) identified 48% of the AD/VD patients as abnormal,
      with 90% agreement with the full BNT's abnormal classifications. An adaptive
      30/15 item version equaled the performance of the full 30 item test while
      requiring only 15 items for 75% of the patients with normal naming ability. This
      study illustrates the utility of IRT for developing neuropsychological assessment
      tools.

PMID- 15742541
TI  - Cross-cultural effects on IQ test performance: a review and preliminary normative
      indications on WAIS-III test performance.
AB  - This article presents a review of cross-cultural influences on Wechsler IQ tests,
      together with a preliminary investigation into WAIS-III test performance (English
      administration) for a southern African sample (age range 19-30) stratified for
      white English first language and black African first language, level and quality
      of education. ('African language' is the term used to denote the indigenous
      languages of black populations in southern Africa). A two-way ANOVA revealed
      highly significant effects for both level and quality of education within the
      black African first language group. Scores for the white English and black
      African first language groups with advantaged education were comparable with the
      US standardization, whereas scores for black African first language participants
      with disadvantaged education were significantly lower than this. Thus indications
      from this research are that normative studies should take account of the
      influential variable of quality of education, in addition to level of education.
      Alternatively faulty conclusions may be drawn about the effects of ethnicity,
      with the potential for neuropsychological misdiagnosis.

PMID- 15742542
TI  - A cross-cultural study with culture fair normative indications on WAIS-III Digit
      Symbol-Incidental Learning.
AB  - The WAIS-III Digit Symbol-Incidental Learning optional procedure, including
      Pairing and Free Recall, was administered to a southern African sample (N=68, age
      range 19-30), which was stratified for ethnicity in association with language of
      origin (white English first language versus black African first language),
      educational level (Grade 12 and Graduate), and quality of education (advantaged
      and disadvantaged). ('African language' is the term used to denote the indigenous
      languages of black populations in southern Africa). Results yielded no
      significant differences for ethnicity/language of origin, level or quality of
      education, indicating that Digit Symbol-Incidental Learning may be a relatively
      culture independent task with utility as a neuropsychological screening
      instrument. Broad normative guidelines are provided for diagnostic purposes, and
      comparisons are made with available norms.

PMID- 15742543
TI  - Verbal fluency component analysis in adults with HIV/AIDS.
AB  - The present study examined the impact of HIV disease severity, depressed mood,
      and highly-active antiretroviral therapy (HAART) on verbal fluency components in
      a sample of adults with HIV-infection. Switching and clustering have been
      identified as dissociable components that contribute to performance on tests of
      phonemic and semantic verbal fluency. Advanced HIV-infection was predicted to
      differentially impair switching. Switching has been shown to be reduced in
      disorders affecting frontal-striatal systems (e.g., Parkinson's disease). Verbal
      fluency protocols (FAS and Animals) of 217 adults with HIV-infection were scored
      for total switches and average cluster size following the method of Troyer, et
      al. (1998). Component scores were compared to published norms. Analysis of
      variance (ANOVA) was used to examine the impact on switching and clustering
      performance of (1) HIV disease severity (presence of AIDS diagnosis) and
      depressed mood, and (2) AIDS diagnosis and medication status (current HAART
      therapy). FAS switching was more often impaired in participants with AIDS.
      Depressed mood did not affect switching. Neither AIDS diagnosis nor depressed
      mood was associated with clustering performance. Participants with an AIDS
      diagnosis who were receiving HAART showed better performance on FAS switching
      relative to participants with AIDS who were not taking antiretroviral medication.
      FAS switching appears to be sensitive to cognitive changes associated with
      advanced HIV-infection. Further research is needed to determine if switching is a
      specific marker of frontal-striatal dysfunction in this population.

PMID- 15742544
TI  - Non-parametric evaluation of memory changes at group and individual level
      following temporal lobe resection for pharmaco-resistant partial epilepsy.
AB  - Group versus individual verbal and visuospatial memory outcome following epilepsy
      surgery was evaluated by a non-parametric method in 25 left and 29 right temporal
      lobectomy patients. Twenty-five controls were assessed twice. Analyses of change
      at an individual level evaluated by this statistical approach based on paired
      ranks were compared to results with a method based on distances (Reliable
      Change). The left temporal lobectomy group deteriorated in the two verbal memory
      variables (p < 0.01 and 0.05). High levels of individual changes unexplained by
      group patterns were disclosed in the three memory variables analyzed in the
      patients. Significant individual change, although less pronounced, also occurred
      in the controls. Group versus individual outcome was adequately distinguished by
      the non-parametric method. To properly analyze memory change after epilepsy
      surgery, evaluation at group and individual level ought to combined.

PMID- 15742545
TI  - Neurocognitive performance in breast cancer survivors exposed to adjuvant
      chemotherapy and tamoxifen.
AB  - The primary aim of the current study was to examine whether neurocognitive
      functioning among breast cancer survivors (BCS) exposed to systemic adjuvant
      chemotherapy differs from that seen among BCS who did not receive chemotherapy.
      The performance of each of these BCS groups was compared to a demographically
      matched comparison group without history of breast cancer, a group not included
      in the majority of previous cognitive functioning studies. We also sought to
      explore whether usage of the anti-estrogen drug tamoxifen, a common component of
      breast cancer treatment, was related to neurocognitive functioning. Finally, we
      wished to examine the relationship between subjective report of cognitive
      functioning and objective performance on neurocognitive measures among BCS. Fifty
      three survivors of breast cancer (all between 2-5 years after diagnosis and
      initial surgical removal of cancerous tissue) and 19 healthy non-BCS comparison
      subjects were administered a comprehensive neurocognitive battery, and measures
      of mood, energy level, and self-reported cognitive functioning. Those BCS who
      received adjuvant chemotherapy performed significantly worse in the domains of
      verbal learning, visuospatial functioning, and visual memory than BCS treated
      with surgery only. Those who received both chemotherapy and tamoxifen showed the
      greatest compromise. Although patients who received chemotherapy (with and
      without tamoxifen) performed worse than those treated with surgery only on
      several domains, neither group was significantly different from demographically
      matched comparison subjects without a history of breast cancer. Finally, we found
      no relationship between subjective cognitive complaints and objective
      performance, although cognitive complaints were associated with measures of
      psychological distress and fatigue. We highlight ways in which these data
      converge with other recent studies to suggest that systemic chemotherapy,
      especially in combination with tamoxifen, can have adverse yet subtle effects on
      cognitive functioning.

PMID- 15742546
TI  - Correcting the 3MS for bias does not improve accuracy when screening for
      cognitive impairment or dementia.
AB  - We investigated the effects of correcting for demographic biases on the
      sensitivity and specificity of the Modified Mini Mental Status Exam (3MS) using a
      sample of English-speaking older adults (N=8901) from the Canadian Studies of
      Health and Aging. The sensitivity and specificity of the original 3MS were
      compared to the 3MS regression-adjusted for the influence of demographic
      variables and then to 3MS percentiles based on published normative data with age
      and education corrected cutoff scores. According to receiver operating
      characteristic curve analyses, the regression-adjusted 3MS was no more accurate
      than the original 3MS when screening for dementia, and it was less accurate when
      screening for cognitive impairment. The use of 3MS percentiles based on normative
      data with age and education corrected cut-off points were less accurate than the
      original 3MS when screening for both cognitive impairment and when screening for
      dementia.

PMID- 15742547
TI  - Reliability and validity of the Rey Visual Design Learning Test in primary school
      children.
AB  - The Rey Visual Design Learning Test (Rey, 1964, in Spreen & Strauss, 1991)
      assesses immediate memory span, new learning and recognition for non-verbal
      material. Three studies are presented that focused on the reliability and
      validity of the RVDLT in primary school children. Test-retest reliability and the
      reliability of the scoring protocol proved satisfactory. A verbalization strategy
      training improved test performance, which indicates that test items are sensitive
      to verbalization. Further research, especially with clinical samples, is needed
      to assess its validity and more normative data needs to be gathered. Suggestions
      for improvements in the test administration are discussed. It is concluded that
      the RVDLT is a potentially useful instrument to measure different aspects of
      visual memory in children.

PMID- 15742548
TI  - [Editorial: Interview with Father Herve Gallais, Conception Hospital, Marseille].

PMID- 15742549
TI  - [Enfuvirtide, first fusion inhibitor in the treatment of human immunodeficiency
      virus infection: mechanism of action and pharmacokinetics].
AB  - Enfuvirtide is a 36 amino-acid synthetic peptide derived from the HR2 sequence of
      the HIV-1 gp41. Enfuvirtide is different from other antiretroviral drugs by its
      extra-cellular action where it binds to the HR1 domain at the viral surface of
      the gp41. The drug inhibits the conformational change of the glycoprotein,
      preventing the intimate fusion between the HIV envelope and the CD4 cell membrane
      and finally the penetration of the viral capside into the target cells. Following
      a 90 mg subcutaneous injection, the plasma concentration rises rapidly to reach a
      4.59 +/- 1.5 microg/ml Cmax between 5 and 7 hours. Residual concentrations are
      between 2.6 and 3.4 microg/ml and the bioavailability of the drug is
      approximately 80%. Plasma concentrations and area under curve are dose-dependant.
      The site of injection does not influence the pharmacokinetic parameters of the
      drug. Infuvirtide is not an inhibitor of the P450 cytochrome and no
      pharmacokinetic interactions have been reported with P450 metabolised drugs.

PMID- 15742550
TI  - [Clinical efficacy and tolerance of enfuvirtide (Fuzeon), new antiretroviral
      inhibitors of intracellular penetration of human immunodeficiency virus (HIV)
      type 1].
AB  - The TORO 1 and TORO 2 clinical trials compared the efficacy and safety of
      enfuvirtide in combination with an optimized background antiretroviral regimen
      and optimized background regimen alone in HIV-1 infected patients. The patients
      had had previous treatment with each of the three classes of antiretroviral drugs
      and had a plasma level of HIV-1 RNA above 5000 copies/ml at baseline. They were
      randomly assigned in a 2:1 ratio to receive either enfuvirtide (90 mg
      subcutaneously twice daily) plus a background regimen optimized with the aid of
      resistance testing, or an optimized antiretroviral regimen alone (control group).
      Six hundred and sixty-one patients were enrolled in the enfuvirtide arm and 334
      in the control group. The median baseline plasma HIV-1 RNA level was 5.2 log10
      copies/ml in the enfuvirtide group and 5.1 log10 copies/ml in the control group.
      Patients had a median of 7 years of previous antiretroviral treatment. The
      optimized background regimen comprised a mean of 4 antiretroviral drugs in both
      groups. At week 48, the mean reduction in viral load was -1.48 log10 copies/ml in
      the enfuvirtide group, and -0.63 log10 copies/ml in the control group (difference
      = 0.846 log10 copies/ml, IC95%: -1.066; -0.626. p < 0.0001). The mean increase in
      the CD4+ cell count was significantly greater in the enfuvirtide group (91
      cells/mm3) than in the control group (45 cells/mm3). Injection site reactions
      were the main reported adverse event which occurred in 98% of the enfuvirtide
      patients. Most had mild to moderate pain or discomfort not requiring analgesic or
      limiting usual activities.

PMID- 15742551
TI  - [Therapeutic indications, antiretroviral treatment optimization and quality of
      life of patients taking enfuvirtide].
AB  - In combination with other antiretroviral drugs, enfuvirtide is indicated in the
      treatment of HIV-1 patients, exposed or with failure to previous therapy with at
      least one of each of the three antiretroviral drugs classes (nucleoside
      inhibitors, non nucleoside inhibitors and protease inhibitors) or intolerant to
      these therapies. Genotypic resistance tests are helpful to evaluate acquired
      resistance to individual drugs, to select the remaining active drugs and to
      eliminate from the background regimen those with characterized resistance. In
      patients receiving enfuvirtide plus an optimized background regimen, the best
      results are reported in those with a baseline CD4+ count above 100/mm3, a plasma
      viral load below 100000 copies/ml, having been previously treated with less than
      10 antiretroviral drugs and having at least 2 active drugs in their background
      regimen. Patients combining these 4 criteria have an 80% chance to have a plasma
      viral load below 400 copies/ml after a 24 weeks course of therapy. In terms of
      Quality of Life, studies demonstrated that patients treated with enfuvirtide have
      improvement in many measures of health-related quality of life, comparatively to
      those receiving the optimized therapy alone.

PMID- 15742552
TI  - Development of matrix-membrane transdermal drug delivery system for atenolol.
AB  - A polymer matrix system for transdermal delivery of Atenolol was developed for
      its prolonged and controlled release systemic availability. To achieve the
      desired and controlled release rate, different combinations of Eudragit RL with
      polyvinyl pyrrolidone and polyethylene glycol 4000 were used in the preparations
      of polymeric matrix system. These preparations were evaluated for in vitro
      release and permeation of the drug across pig skin. The desired systems exhibited
      linear relationship between drug release (Q) versus ne0.8(hr0.8). The product
      exhibiting required skin permeation 64 mcg/h/cm2 to achieve an effective plasma
      concentration was selected for the in vivo performance evaluation. The drug
      plasma profile was compared with the plasma profile obtained following the
      administration of a conventional oral dose of Atenolol. The study revealed that
      the designed polymeric matrix transdermal drug delivery system of Atenolol could
      be successful with improved performance.

PMID- 15742553
TI  - Solvent-free protein encapsulation within biodegradable polymer foams.
AB  - Microporous poly(D,L-lactide-co-glycolide) matrices containing encapsulated
      proteins were fabricated in a solvent-free manner. Microporous foam was generated
      by saturating a mixture of polymer and protein particles in supercritical carbon
      dioxide (SC-CO2), dispersing the protein particles in the polymer melt followed
      by a rapid evaporation of the CO2 phase. The release rates of protein
      encapsulated within porous poly(lactide-co-glycolide)(PLGA) constructs produced
      in SC-CO2 were measured in vitro. Although a substantial amount of protein was
      released within the first 48 h, results indicated that protein may be dispersed
      throughout the polymer phase and released over 3 weeks using this solvent-free
      technique. Basic fibroblast growth factor (bFGF), known to promote angiogenesis
      in vivo, was encapsulated within the polymer matrix. In addition, retention of
      biological activity was measured for bFGF encapsulated within PLGA foams.
      Encapsulated bFGF was released from the porous constructs for up to 10 days in
      vitro with little loss of biological activity.

PMID- 15742554
TI  - Intranasal bioavailability of insulin from carbopol-based gel spray in rabbits.
AB  - The purpose of this study was to investigate the nasal absorption of insulin from
      a carbopol-based nasal gel spray in rabbits. An insulin nasal gel was prepared by
      dispersing carbopol in distilled water, followed by the addition of insulin
      solution, then neutralization and viscosity adjustment. The nasal absorption of
      insulin from the gel, in conscious rabbits, was evaluated in comparison with
      absorption from an insulin solution. The absolute bioavailability of insulin from
      the nasal gel was studied using blood glucose level in comparison to intravenous
      injection. The insulin gel formulation produced a significant hypoglycemic
      response in rabbits, whereas no response was seen following administration of the
      insulin solution formulation. The bioavailability of insulin from the nasal gel
      formulation was 20.6% compared with the intravenous injection. The results of the
      present study suggest that the carbopol gel promotes the nasal absorption of
      insulin in rabbit model and due to its sprayability with commercially available
      spray pumps, could be considered as a preferred platform in nasal drug
      administration.

PMID- 15742556
TI  - Design and study of rifampicin oral controlled release formulations.
AB  - Oral controlled release formulations of rifampicin have been developed by using
      hydroxypropyl methylcellulose polymer at different ratios. From in vitro release
      data, we found that the release was extended with an increase of polymer
      proportion from 20% to 40%. However, increase in polymer beyond 40% resulted in
      no significant change in the release rate. There was a distinct difference in the
      release rate and release character due to variation in the compression force. The
      release kinetics were analyzed using Ritger and Peppas exponential equation.
      Stability studies at ambient storage conditions for 1 year showed that
      formulations were stable.

PMID- 15742555
TI  - The effect of RMP-7 and its derivative on transporting Evans blue liposomes into
      the brain.
AB  - To investigate the effect of RMP-7 and its derivative on drug transport across
      blood brain barrier (BBB), RMP-7 and DSPE-PEG-NHS [1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine-n-[poly(ethyleneglycol)]-hydroxy succinamide, PEG M 3400]
      were conjugated under mild conditions and the reaction ratio was determined using
      MALDI-TOF-MS (matrix-assisted laser desorption-ionization time-of-flight mass
      spectrometry). An endothelial cell monolayer in vitro BBB model was established
      and used to determine the bioactivity of RMP-7 and its derivative "opening BBB."
      Horse radish peroxide (HRP), liposome (HRP-L-PEG), and Evans blue (EB) liposome
      (EB-L-PEG) were prepared using the reverse-phase evaporation method. HRP-L-PEG
      RMP-7 and EB-L-PEG-RMP-7 were obtained by inserting DSPE-PEG-RMP-7 into the
      surface of liposome. The bioactivity of RMP-7 and DSPE-PEG-RMP-7 opening BBB were
      evaluated to determine their effect on the permeation ratio of HRP and HRP
      liposome across the in vitro BBB model. To evaluate the in vivo bioactivity of
      RMP-7 and DSPE-PEG-RMP-7 on EB transport across BBB into the brain, the indicated
      compounds were administered to rats. Then, brain slices were analyzed using
      confocal laser scanning microcopy and the EB concentration in the brain, liver,
      spleen, lung, and kidney was determined using the formamide-extraction
      ultraviolet-spectrophotometric method. The results demonstrated that RMP-7 was
      conjugated with DSPE-PEG-NHS at the molecular ratio of 1:1 and the product is
      DSPE-PEG-RMP-7. Compared with adding HRP alone, RMP-7 and DSPE-PEG-RMP-7 improved
      2- to 3-fold the transport of HRP in the in vitro BBB model. The in vivo
      experiments showed that DSPE-PEG-RMP-7 was better at facilitating EB transport
      into brain than RMP-7. The reason may be that DSPE-PEG-RMP-7 can "open BBB" as
      soon as the EB-L-PEG-RMP-7 reaches BBB.

PMID- 15742557
TI  - Treatment of focal cerebral ischemia with liposomal nerve growth factor.
AB  - Liposomal nerve growth factor (NGF) was used for the treatment of focal cerebral
      ischemia in a rat model. Positive charge inducing agents of sphingosine (SP) and
      stearylamine (S) were formulated in the liposomal NGF. Dose-response of
      intraventricular injection of liposomal NGF showed significant reduction in
      infarct volume at the dose of 5 and 10 microg/rat of NGF. The liposomal NGF
      formulated with SP or S demonstrated similar results in the reduction of total
      infarct volume in rats. When we increased the molar ratio of SP and S from 0.15
      to 0.3, the infarct volume from rats showed a similar value as that of the
      control treated with NGF solution. Liposomal NGF was given prior to the
      development of ischemia. We found that NGF was effective in prevention of
      neuronal death. The NGF concentrations in brain for liposomal NGF were maintained
      in a level significantly higher than those for NGF solution. This was attributed
      to the positively charged liposomal NGF bound effectively in brain ventricle and
      caused longer retention time than free NGF for localization in brain. Therefore,
      the effect of liposomal NGF on reduction of infarct volume was significant. We
      assumed that the transportation of NGF might go through the cerebrospinal fluid
      pathway throughout the ventricular system and subarachnoid system to cerebral
      cortex to produce a therapeutic effect on ischemia.

PMID- 15742558
TI  - An improved thick-film piezoelectric material by powder blending and enhanced
      processing parameters.
AB  - This paper details improvements of the d33 co-efficient for thick-film lead
      zirconate titanate (PZT) layers. In particular, the effect of blending ball and
      attritor milled powders has been investigated. Mathematical modeling of the film
      structure has produced initial experimental values for powder combination
      percentages. A range of paste formulations between 8:1 and 2:1 ball to attritor
      milled PZT powders by weight have been mixed into a screen-printable paste. Each
      paste contains 10% by weight of lead borosilicate glass and an appropriate
      quantity of solvent to formulate a screen printable thixotropic paste. A d33 of
      63.5 pC/N was obtained with a combination of 4:1 ball milled to attritor milled
      powder by weight. The improved paste combines the high d33 values of ball and the
      consistency of attritor milled powder. The measured d33 coefficient was further
      improved to 131 pC/N by increasing the furnace firing profile to 1000 degrees C,
      increasing the poling temperature to 200 degrees C, and using gold cermet and
      polymer electrodes that avoid silver migration effects and repeated firing of the
      PZT film.

PMID- 15742559
TI  - Distributed bragg reflector resonators with cylindrical symmetry and extremely
      high Q-factors.
AB  - A simple non-Maxwellian method is presented that allows the approximate solution
      of all the dimensions of a multilayered dielectric TE0qp mode cylindrical
      resonant cavity that constitutes a distributed Bragg reflection (DBR) resonator.
      The analysis considers an arbitrary number of alternating dielectric and free
      space layers of cylindrical geometry enclosed by a metal cylinder. The layers may
      be arranged along the axial direction, the radial direction, or both. Given only
      the aspect ratio of the cavity, the desired frequency and the dielectric
      constants of the material layers, the relevant dimensions are determined from
      only a set of simultaneous equations, and iterative techniques are not required.
      The formulas were verified using rigorous method of lines (MoL) calculations and
      previously published experimental work. We show that the simple approximation
      gives dimensions close to the values of the optimum Bragg reflection condition
      determined by the rigorous analysis. The resulting solution is more compact with
      a higher Q-factor when compared to other reported cylindrical DBR structures.
      This is because it properly takes into account the effect of the aspect ratio on
      the Bragg antiresonance condition along the z-axis of the resonator. Previous
      analyses assumed the propagation in the z-direction was independent of the aspect
      ratio, and the layers of the Bragg reflector were a quarter of a wavelength thick
      along the z-direction. When the aspect ratio is properly taken into account, we
      show that the thickness of the Bragg reflectors are equivalent to the thickness
      of plane wave Bragg reflectors (or quarter wavelength plates). Thus it turns out
      that the sizes of the reflectors are related to the free-space propagation
      constant rather than the propagation constant in the z-direction.

PMID- 15742560
TI  - Coupled tangential-axial resonant modes of piezoelectric hollow cylinders and
      their application in ultrasonic motors.
AB  - This paper describes a tangential-axial eigen-mode of a piezoelectric hollow
      cylinder. A new type of piezoelectric ultrasonic motor using this oscillation
      mode has been developed. The motor is a traveling-wave-type motor. The stator of
      such a motor consists of a solid piezoelectric hollow cylinder, which, excited in
      the tangential-axial resonant mode by a three-phase electrical signal, will
      exhibit elliptical displacement and transfer rotation to the rotor. The behavior
      of the stator has been simulated with finite element method (FEM) software. The
      simulation results have been checked with single-point contact measurements on
      the surface of the ultrasonic motors. The paper closes with the introduction of
      new ultrasonic motors based on this oscillation mode.

PMID- 15742561
TI  - Coherent-array imaging using phased subarrays. Part I: basic principles.
AB  - The front-end hardware complexity of a coherent array imaging system scales with
      the number of active array elements that are simultaneously used for transmission
      or reception of signals. Different imaging methods use different numbers of
      active channels and data collection strategies. Conventional full phased array
      (FPA) imaging produces the best image quality using all elements for both
      transmission and reception, and it has high front-end hardware complexity. In
      contrast, classical synthetic aperture (CSA) imaging only transmits on and
      receives from a single element at a time, minimizing the hardware complexity but
      achieving poor image quality. We propose a new coherent array imaging method-
      phased subarray (PSA) imaging--that performs partial transmit and receive beam
      forming using a subset of adjacent elements at each firing step. This method
      reduces the number of active channels to the number of subarray elements; these
      channels are multiplexed across the full array and a reduced number of beams are
      acquired from each subarray. The low-resolution subarray images are laterally
      upsampled, interpolated, weighted, and coherently summed to form the final high
      resolution PSA image. The PSA imaging reduces the complexity of the front-end
      hardware while achieving image quality approaching that of FPA imaging.

PMID- 15742562
TI  - Coherent array imaging using phased subarrays. Part II: simulations and
      experimental results.
AB  - The basic principles and theory of phased subarray (PSA) imaging imaging provides
      the flexibility of reducing the number of front-end hardware channels between
      that of classical synthetic aperture (CSA) imaging--which uses only one element
      per firing event--and full-phased array (FPA) imaging-which uses all elements for
      each firing. The performance of PSA generally ranges between that obtained by CSA
      and FPA using the same array, and depends on the amount of hardware complexity
      reduction. For the work described in this paper, we performed FPA, CSA, and PSA
      imaging of a resolution phantom using both simulated and experimental data from a
      3-MHz, 3.2-cm, 128-element capacitive micromachined ultrasound transducer (CMUT)
      array. The simulated system point responses in the spatial and frequency domains
      are presented as a means of studying the effects of signal bandwidth,
      reconstruction filter size, and subsampling rate on the PSA system performance.
      The PSA and FPA sector-scanned images were reconstructed using the wideband
      experimental data with 80% fractional bandwidth, with seven 32-element subarrays
      used for PSA imaging. The measurements on the experimental sector images indicate
      that, at the transmit focal zone, the PSA method provides a 10% improvement in
      the 6-dB lateral resolution, and the axial point resolution of PSA imaging is
      identical to that of FPA imaging. The signal-to-noise ratio (SNR) of PSA image
      was 58.3 dB, 4.9 dB below that of the FPA image, and the contrast-to-noise ratio
      (CNR) is reduced by 10%. The simulated and experimental test results presented in
      this paper validate theoretical expectations and illustrate the flexibility of
      PSA imaging as a way to exchange SNR and frame rate for simplified front-end
      hardware.

PMID- 15742563
TI  - High frequency nonlinear B-scan imaging of microbubble contrast agents.
AB  - It previously was shown that it is possible to produce nonlinear scattering from
      microbubble contrast agents using transmit frequencies in the 14-32 MHz range,
      suggesting the possibility of performing high-frequency, nonlinear microbubble
      imaging. In this study, we describe the development of nonlinear microbubble B
      scan imaging instrumentation capable of operating at transmit center frequencies
      between 10 and 50 MHz. The system underwent validation experiments using transmit
      frequencies of 20 and 30 MHz. Agent characterization experiments demonstrate the
      presence of nonlinear scattering for the conditions used in this study. Using
      wall-less vessel phantoms, nonlinear B-scan imaging is performed using energy in
      one of the subharmonic, ultraharmonic, and second harmonic frequency regions for
      transmit frequencies of 20 and 30 MHz. Both subharmonic and ultraharmonic imaging
      modes achieved suppression of tissue signals to below the noise floor while
      achieving contrast to noise ratios of up to 26 and 17 dB, respectively. The
      performance of second harmonic imaging was compromised by nonlinear propagation
      and offered no significant contrast improvement over fundamental mode imaging. In
      vivo experiments using the subharmonic of a 20 MHz transmit pulse show the
      successful detection of microvessels in the rabbit ear and in the mouse heart.
      The results of this study demonstrate the feasibility of nonlinear microbubble
      imaging at high frequencies.

PMID- 15742564
TI  - A spline-based algorithm for continuous time-delay estimation using sampled data.
AB  - Time delay estimation (TDE) lies at the heart of signal processing algorithms in
      a broad range of application areas, including communications, coherent imaging,
      speech processing, and acoustics. In medical ultrasound for example, TDE is used
      in blood flow estimation, tissue motion measurement, tissue elasticity
      estimation, phase aberration correction, and a number of other algorithms.
      Because of its central significance, TDE accuracy, precision, and computational
      cost are of critical importance. Furthermore, because TDE is typically performed
      on sampled signals-and delay estimates are usually desired over a continuous
      domain-time delay estimator performance should be considered in conjunction with
      associated interpolation. In this paper we present a new time-delay estimator
      that directly determines continuous time-delay estimates from sampled data. The
      technique forms a spline-based, piecewise continuous representation of the
      reference signal then solves for the minimum of the sum squared error between the
      reference and the delayed signals to determine their relative time delay.
      Computer simulation results clearly show that the proposed algorithm
      significantly outperforms other algorithms in terms of jitter and bias over a
      broad range of conditions. We also describe a modified version of the algorithm
      that includes companding with only a minor increase in computational cost.

PMID- 15742565
TI  - Effect of red cell clustering and anisotropy on ultrasound blood backscatter: a
      Monte Carlo study.
AB  - When flowing at a low shear rate, blood appears hyperechogenic on ultrasound B
      scans. The formation of red blood cell (RBC) aggregates that also alters blood
      viscosity is the microscopic mechanism explaining this acoustical phenomenon. In
      this study, Monte Carlo simulations were performed to predict how RBC clustering
      increases ultrasound scattering by blood. A bidimensional Gibbs-Markov random
      point process parameterized by the adhesion energy epsilon and an anisotropy
      index nu was used to describe RBC positions for a hematocrit H = 40%. The
      frequency dependence of the backscattering coefficient chi(f) was computed using
      Born approximation. The backscattering coefficient chi0 at 5 MHz and the spectral
      slopes n(x) and n(y) (chi alpha f(nx) or f(ny)) measured, respectively, when the
      insonification is parallel and perpendicular with the RBC cluster axis were then
      extracted. Under isotropic conditions, chi0 increased up to 7 dB with epsilon and
      n(x) = n(y) decreased from 4.2 to 3.4. Under anisotropic conditions, the
      backscattering was stronger perpendicularly to aggregate axis, resulting in n(x)
      < n(y). The anisotropy in scattering appeared more pronounced when epsilon or nu
      increased. These two dimensional results generally predict that low-frequency
      blood backscatter is related to cluster dimension, and higher-frequency
      properties are affected by finer morphological features as anisotropy. This
      numerically establishes that ultrasound backscatter spectroscopy on a large
      frequency range is pertinent to characterize in situ hemorheology.

PMID- 15742566
TI  - Optical observations of acoustical radiation force effects on individual air
      bubbles.
AB  - Previous studies dealing with contrast agent microbubbles have demonstrated that
      ultrasound (US) can significantly influence the movement of microbubbles. In this
      paper, we investigated the influence of the acoustic radiation force on
      individual air bubbles using high-speed photography. We emphasize the effects of
      the US parameters (pulse length, acoustic pressure) on different bubble patterns
      and their consequences on the translational motion of the bubbles. A stream of
      uniform air bubbles with diameter ranging from 35 microm to 79 microm was
      generated and insonified with a single US pulse emitted at a frequency of 130
      kHz. The bubble sizes have been chosen to be above, below, and at resonance. The
      peak acoustic pressures used in these experiments ranged from 40 kPa to 120 kPa.
      The axial displacements of the bubbles produced by the action of the US pulse
      were optically recorded using a high-speed camera at 1 kHz frame rate. The
      experimental results were compared to a simplified force balance theoretical
      model, including the action of the primary radiation force and the fluid drag
      force. Although the model is quite simple and does not take into account
      phenomena like bubble shape oscillations and added mass, the experimental
      findings agree with the predictions. The measured axial displacement increases
      quasilinearly with the burst length and the transmitted acoustic pressure. The
      axial displacement varies with the size and the density of the air bubbles,
      reaching a maximum at the resonance size of 48 microm. The predicted displacement
      values differ by 15% from the measured data, except for resonant bubbles for
      which the displacement was overestimated by about 40%. This study demonstrates
      that even a single US pulse produces radiation forces that are strong enough to
      affect the bubble position.

PMID- 15742567
TI  - Extraction of the SAW attenuation parameter in periodic reflecting gratings.
AB  - In this paper, the extraction of the coupling-of-modes (COM) model attenuation
      parameter gamma in a finite grating is considered. We use test structures
      comprising identical transmitting and receiving transducers and a grating
      centered in the acoustic channel along the propagation direction of the surface
      acoustic wave (SAW). The extraction procedure proposed is based on studying the
      magnitude of the ratio of the reflection and transmission coefficients of the
      grating, R/T, obtained through time gating from the S parameter measurements of
      the test devices. In particular, we found that the level of the notches of R/T
      directly depends on the attenuation of SAW in the grating. A simple closed-form
      expression for the attenuation normalized to the grating length, gamma lambda0,
      depending on the characteristics of absolute value R/T, is given. The proposed
      method is applied to the measurement data for selected grating topologies to
      yield estimates of the attenuation.

PMID- 15742568
TI  - New architectures for feedthrough SAW recursive devices.
AB  - This paper presents an analysis of a new type of feedthrough recursive surface
      acoustic wave (SAW) device. The device combines a conventional SAW structure with
      positive feedback in a way that allows use of selective properties of the SAW
      structure, control of the central frequency and bandwidth, achieving
      significantly higher quality factors for given dimensions of the structure, and
      reduction of the sidelobe level. Several possible implementations are discussed
      from a simple one that uses external circuitry to the most advanced that includes
      digital supervisory control. Equations are presented that relate the central
      frequency, bandwidth, and sidelobe level to the parameters of the SAW structure
      and feedback loop. The simulation results were found to be in good agreement with
      experimental data. These data show the control of the central frequency within
      1%, a 10-fold increase in the quality factor compared to the original SAW
      structure, and a reduction of the side-lobe level by 20 dB irrespective of the
      influence of second order effects and random manufacturing fluctuations.

PMID- 15742569
TI  - Half-thickness inversion layer high-frequency ultrasonic transducers using LiNbO3
      single crystal.
AB  - Half-thickness inversion layer high-frequency ultrasonic transducers were
      fabricated using lithium niobate (LiNbO3) single crystal plate. The transducers
      developed for this study used a 36 degrees rotated Y-cut LiNbO3 thin plate with
      an active element thickness of 115 microm. The designed center frequency was in
      the range of 30 to 60 MHz. Half-thickness inversion layer was formed after the
      sample was annealed at a high temperature, and it is shown that the inversion
      layer thickness can be controlled by the temperature. Silver powder/epoxy
      composite and parylene were used as acoustic matching layers. A lossy silver
      epoxy was used as the backing material. Using an analytical method, the
      electrical impedance for different inversion layer ratios was determined. The
      measured resonant frequency was consistent with the modeled data. Even-order
      higher frequency broadband ultrasonic transducers with a center frequency at 60
      MHz was obtained using half-thickness inversion layer of LiNbO3 single crystal.

PMID- 15742570
TI  - Bidirectional linear ultrasonic motor using longitudinal vibrating transducers.

PMID- 15742571
TI  - Vibrations of an isotropic elastic wedge.

PMID- 15742572
TI  - Surface acoustic waves on X-cut LiNbO3.

PMID- 15742573
TI  - Preparing for a JCAHO survey: tips for the clinical nutrition department.

PMID- 15742574
TI  - Paid feeding assistants: federal regulations are being challenged.

PMID- 15742575
TI  - Mission, margin, and trust in the nonprofit health care enterprise.

PMID- 15742576
TI  - The battle over self-insured health plans, or "one good loophole deserves
      another".

PMID- 15742577
TI  - Breathing life into the Framework Convention on Tobacco Control: smoking
      cessation and the right to health.

PMID- 15742578
TI  - Pharmaceutical arbitrage: balancing access and innovation in international
      prescription drug markets.

PMID- 15742579
TI  - Using reciprocity to motivate organ donations.

PMID- 15742580
TI  - Effective legal reform and the malpractice insurance crisis.

PMID- 15742581
TI  - Debunking medical malpractice myths: unraveling the false premises behind "tort
      reform".

PMID- 15742582
TI  - Health care in crisis: the need for medical liability reform.

PMID- 15742583
TI  - Turning from damage caps to information disclosure: an alternative to tort
      reform.

PMID- 15742584
TI  - Gene patents: the need for bioethics scrutiny and legal change.

PMID- 15742585
TI  - World health law: toward a new conception of global health governance for the
      21st century.

PMID- 15742586
TI  - The challenge of assuring continued post-trial access to beneficial treatment.

PMID- 15742587
TI  - The most important health care legislation of the millennium (so far): the
      Medicare Modernization Act.

PMID- 15742588
TI  - The swinging pendulum: the Supreme Court reverses course on ERISA and managed
      care.

PMID- 15742589
TI  - Inequality, infections, and community-based health care.

PMID- 15742590
TI  - Medicare reform and social insurance: the clashes of 2003 and their potential
      fallout.

PMID- 15742591
TI  - The pedagogical significance of the Bush stem cell policy: a window into
      bioethical regulation in the United States.

PMID- 15742592
TI  - A second course of hylan G-F 20 for the treatment of osteoarthritic knee pain: 12
      month patient follow-up.
AB  - This prospective open-label study evaluated the efficacy and tolerability of a
      second course of hylan G-F 20 for the treatment of osteoarthritic knee pain over
      a 12-month period in patients who previously experienced a beneficial initial
      course of therapy. Men or women aged > or = 40 years with knee osteoarthritis
      received 3 weekly injections of hylan G-F 20. Consecutive patients requesting a
      second course of therapy were enrolled from October 2000 to January 2001. The
      mean time between the first and second courses of hylan G-F 20 was 19.6 months.
      All efficacy parameters significantly improved (P<.001) from baseline at weeks 1,
      2, 4, 8, 12, 26, and 52. Improvements from baseline to weeks 26 and 52 for the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) index
      question A1, WOMAC domain C, and total WOMAC were 1.39+/-0.11 and 1.1+/-0.12,
      18.50+/-1.43 and 13.69+/-1.54, and 26.77+/-1.97 and 19.8+/-2.13, respectively.
      Significant improvements from baseline were maintained for patient and physician
      VAS to week 26 (patient: 48.66+/-2.52; investigator: 51.51+/-2.34) and week 52
      (patient: 46.10+/-2.73; investigator: 47.23+/-2.52). A second course of hylan G-F
      20 therapy was generally well-tolerated; the types of local events observed in
      this study were not qualitatively different from those in the current product
      information and published literature. For continued relief of osteoarthritic knee
      pain, this study supports repeat use of hylan G-F 20 in patients who had a
      previous successful course of therapy.

PMID- 15742593
TI  - Comparison of the analgesic effects of intra-articular injections administered
      preoperatively and postoperatively in knee arthroscopy.
AB  - Perioperative injection of analgesic agents is widely used for postoperative pain
      control following knee arthroscopy. This prospective, randomized, double-blind
      study explored whether a preoperative analgesic injection offered better pain
      control than a postoperative injection. Patients undergoing knee arthroscopy
      under general anesthesia were randomized to receive a standardized combination of
      intra-articular bupivacaine, morphine, and epinephrine administered either 20
      minutes prior to incision or at the end of the procedure. Outcome measures
      included visual analog pain scores at 0, 30, 60, 90, and 120 minutes after the
      procedure, total recovery room fentanyl consumption, total oral narcotics
      consumption for the first 24 hours after surgery, and a validated pain and
      satisfaction instrument. Of the 22 patients enrolled in the study, 21
      successfully completed the study protocol. Pain scores, narcotics consumption,
      and overall patient satisfaction were not significantly different between the two
      groups. These findings indicate the timing of intra-articular analgesic
      injections during outpatient knee arthroscopy, either preoperatively or
      postoperatively, may be at the discretion of the surgeon.

PMID- 15742594
TI  - Tissue engineering for meniscus repair.
AB  - Meniscus injury is common in today's active society. Despite the frequent
      presentation of meniscus injury, the decision to repair or resect a torn meniscus
      is not always straightforward. Current repair techniques are effective in the
      peripheral vascularized meniscus, but their success is not dependable in the
      avascularized zone. Tissue engineering, a discipline that combines the
      technologies of cell culture and biodegradable scaffolds to deliver a cellular
      repair, may be one future answer to this problem. The concept of using cell-based
      repair for torn menisci could improve healing of lesions in the avascular zone
      and broadly expand the indication for repair rather than removal, obviating the
      need for meniscectomy. This article reviews current advances in the relatively
      new field of tissue engineering toward the development of a tissue-engineered
      meniscal repair technique.

PMID- 15742596
TI  - MRI and histologic evaluation of two cases of osteochondral autograft
      transplantation procedures.

PMID- 15742595
TI  - In vivo transplantation of neonatal ovine neocartilage allografts: determining
      the effectiveness of tissue transglutaminase.
AB  - Following transplantation of ovine neocartilage allografts, 26 sheep were divided
      into groups according to the following weight-bearing schedule: 8-week nonweight
      bearing (8NWB, n=14), and 8-week nonweight bearing+4-week weight bearing
      (8NWB+4WB, n=12). In addition, 7 and 6 sheep, respectively, in the 8NWB and
      8NWB+4WB groups received tTG treatment after allograft transplantation, whereas
      the remaining 13 sheep in these groups did not receive tTG. Finally, 8 sheep
      served as sham-operated controls without allograft transplantation. After
      euthanasia, stifle joints were harvested for the analysis of gross appearance,
      chondrocyte viability, histology, and biomechanical testing. No significant
      differences were noted in macroscopic graft survival and union with host tissue
      in both 8NWB and 8NWB+4WB groups between the tTG treated and non-tTG treated
      animals. Analysis of histological scores demonstrated no significant difference
      between tTG and non-tTG treatments in both 8NWB and 8NWB+4WB groups. Confocal
      laser microscopic analysis of the explanted defects revealed 70%-100% cell
      viability in all treatment groups. This study shows that allogeneic chondrocytes
      harvested from neonatal donors provide sufficient metabolic activity to affect
      repair. Use of tTG to augment resorbable suture fixation of neocartilage grafts
      provided no advantage over suture alone in this pilot study.

PMID- 15742597
TI  - Small area variation in orthopedics.
AB  - It is clear that small area variation exists in orthopedics, but there is still
      much to learn. Given the many unanswered questions regarding area variation,
      regulatory policy at this time would be premature. The biggest piece of the
      puzzle that needs to be solved is the influence of disease prevalence and
      severity. While it seems unlikely this will explain all of the variation, it is
      equally unlikely that musculoskeletal diseases are distributed evenly across
      geopolitical boundaries, hence, it likely accounts for some of the observed
      variation. More patient-level studies need to be conducted in non-Medicare
      populations. For example, the extent to which area variation exists in sports
      medicine and knee surgery for younger patients is unknown. Profiling is likely
      here to stay. In accord, it should be exploited by the orthopedic community for
      its strengths while keeping in mind its limitations. Orthopedic surgeons should
      be at the forefront of this research and consequently influential in its
      evolution rather than have the managed care industry or government dictate
      policy.

PMID- 15742598
TI  - Evidence-based medicine for orthopedic surgeons.
AB  - Evidence-based medicine is a rational, logical approach for clinicians to make
      decisions about how to handle the large amount of new medical information. Its
      basis is the scientific method. The practicing clinician need understand only a
      few simple concepts to use this approach, and in doing so will provide the best
      available care to the patients.

PMID- 15742599
TI  - Randomized controlled trials in knee surgery.
AB  - Randomized controlled trials are complex, require great effort and attention to
      detail by the investigator, and are expensive. This research methodology is
      important to allow us to base our decision-making for patients on solid evidence
      to ultimately improve patient care.

PMID- 15742600
TI  - Knee sports injury outcome measures.

PMID- 15742601
TI  - Relationship between subjective and objective assessment of outcomes after
      anterior cruciate ligament reconstruction.

PMID- 15742602
TI  - Reducing knee and anterior cruciate ligament injuries among female athletes: a
      systematic review of neuromuscular training interventions.
AB  - There is evidence that neuromuscular training not only decreases the potential
      biomechanical risk factors for ACL injury, but also decreases knee and,
      specifically, ACL injury incidence in female athletes. Five of the six
      interventions in this systematic review demonstrated significant effects on
      overall knee or ACL injury rates. It appears that plyometric power, biomechanics
      and technique, strength, balance, and core stability training can induce
      neuromuscular changes and potential injury prevention effects in female athletes.
      However, it is unknown which of these components is most effective or whether the
      effects are combinatorial. Future research should assess the relative efficacy of
      these interventions alone and in combination to achieve the optimal effect in the
      most efficient manner possible. Selective combination of neuromuscular training
      components may provide additive effects, further reducing the risk of ACL
      injuries in female athletes. Additional research directions include the
      assessment of relative injury risk using mass neuromuscular screening, the
      development of more specific injury prevention protocols targeted toward high
      risk athletes, and the determination of when these interventions should be
      implemented. It may be that prepubertal or early pubertal female athletes may
      have the potential to achieve optimal biomechanical changes and the greatest
      chance of injury-free sports participation throughout their careers.

PMID- 15742603
TI  - Stem cell therapies for neuromuscular diseases.
AB  - The promise of stem cells for therapy of a variety of disease conditions is one
      of the most heavily marketed commodities of modern biotechnology. Interest in
      this prospect has opened up and destabilized a large area of developmental
      biology, challenging some of its major tenets, and becoming a source of
      controversy. Much of the disagreement arises from apparently simple conflicts of
      findings, which may have as much to do with differences of interpretation as of
      actual data. However, outside a few favoured situations, the practical
      significance of most of the findings is marginal, with only trivial levels of
      stem cell participation in tissue reconstruction. Currently, much of the effort
      in stem cell research is devoted to identifying sources of stem cells and the
      diversity of fates they can be induced to adopt. Areas that are in need of
      development are those concerned with delivery to target tissues, improvement of
      conversion to the desired cell types and effectiveness of functional integration
      of these cells into the target tissue. Of these hurdles, perhaps the most
      important is the efficient delivery of stem cells to the appropriate sites. The
      most promising results in this respect have been achieved by either targeted
      injection to discrete sites or, for more diffuse targets, delivery via the
      intermediary of a bone marrow transplant. For the latter especially, we need a
      degree of improvement that can only come from a better understanding of the
      mechanisms involved.

PMID- 15742604
TI  - Neuropathological and molecular aspects of low-grade and high-grade gliomas.
AB  - Gliomas are the most frequent primary brain tumors. They are derived from glial
      cells of astrocytic, oligodendroglial and ependymal origin. According to the WHO
      classification of brain tumors gliomas are divided in low-grade (grades I and II)
      and high-grade (grades III and IV) tumors. Low-grade tumors are well
      differentiated, slow-growing lesions. Grade I tumors are well-circumscribed and
      often surgically curable, whereas grade II tumors are diffuse, infiltrating
      lesions with a marked potential over time for progression towards a high-grade
      malignant tumor. The optimal management of low-grade gliomas is still debated.
      Important prognostic factors such as histology, grade and location of the tumor,
      age and functional status of the patient, must be taken into consideration to
      select the most appropriate treatment. Major advances in the molecular genetic
      assessment of brain tumors and of gliomas in particular have lead to the
      identification of several molecular markers playing a crucial role in the
      development of gliomas and in their malignant transformation. Some of those
      markers were found very useful to assist in the histological diagnosis and to
      predict survival and response to therapy. A combined deletion of chromosomes arms
      1p and 19q can be found in more than 50% of Grade II and III oligodendrogliomas
      and has been associated with chemosensitivity and a better prognosis. Once
      limited to the field of research, molecular biology has now entered the daily
      neuropathological practice and will undoubtedly play an increasing role in future
      classification and treatment of brain tumors.

PMID- 15742605
TI  - Factors affecting one year mortality and functional outcome after first ever
      ischemic stroke in the region of Antalya, Turkey (a hospital-based study).
AB  - In order to establish good health politics for stroke survivors, regional
      differences in factors affecting the outcome of patients have to be known. For
      this purpose we investigated factors affecting 1 year mortality and functional
      outcome in patients with first-ever-in a lifetime stroke in the region of
      Antalya, Turkey. One-hundred and forty-seven patients with a first ever stroke
      were included and followed up for at least one year. The modified Rankin Scale
      was used for evaluation of handicap. Several factors known to affect prognosis
      such as demographic features, socioeconomic status, stroke subtype, neurological
      findings and stroke risk factors were compared between patients who died during
      follow-up and survivors. Of the 147 patients 35 (23.8%) died during the course of
      the study. Multivariate logistic regression analysis showed that only illiteracy,
      being single or widowed and presence of urinary incontinence were significant
      predictors of being dead at the end of 1 year. In the survivors factors
      independently affecting dependence at the end of one year were age, presence of
      coma on admission and urinary incontinence. Our results suggest that not only
      stroke severity but also socioeconomic variables are important in determining the
      prognosis of stroke patients.

PMID- 15742606
TI  - Is Helicobacter pylori infection a risk factor for migraine? A case-control
      study.
AB  - BACKGROUND: The relation between Helicobacter pylori and Migraine and usefulness
      of the eradication treatment on headache is controversial. The aim of this study
      was to determine whether Helicobacter pylori infection is a risk factor for
      migraine and whether the eradication of the bacterium can reduce frequency,
      duration and severity of clinical attacks of the disease. METHODS: A total 70
      consecutive patients with migraine with aura and without aura who came to
      Gastroenterology polyclinic with various complaints were enrolled in the study
      and compared with a group of 60 matched controls. Helicobacter pylori infection
      was diagnosed by histopathological biopsies, which was taken by endoscopy
      (Olympus-GIFXQ240 endoscope). The diagnosis and classification of migraine was
      made according to the International Headache Society (IHS) criteria. We assessed
      the frequency, duration and severity of clinical attacks of migraine before and
      after eradication treatment. The eradication control of Helicobacter pylori was
      made by Helicobacter pylori fecal antigen test by PCR after 2 months. RESULTS:
      Helicobacter pylori positiveness is more relevant in the migranous patients
      compared with controls. 84.6% of patients with eradication treatment and 75% of
      classically treated patients informed to get benefit from the treatment.
      CONCLUSION: Helicobacter pylori should be examined in migranous patients and
      eradication of the infection may be helpful for the treatment of the disease.

PMID- 15742607
TI  - Could visual neglect induce amblyopia?
AB  - Oculomotor nerve disease is a common cause of diplopia. When strabismus is
      present, absence of diplopia has to induce the research of either uncovering of
      visual fields or monocular suppression, amblyopia or blindness. We describe the
      case of a 41-year-old woman presenting with right oculomotor paresis and left
      object-centred visual neglect due to a right fronto-parietal haemorrhage
      expanding to the right peri-mesencephalic cisterna caused by the rupture of a
      right middle cerebral artery aneurysm. She never complained of diplopia despite
      binocular vision and progressive recovery of strabismus, excluding uncovering of
      visual fields. Since all other causes were excluded in this case, we hypothesise
      that the absence of diplopia was due to the object-centred visual neglect.
      Partial internal right oculomotor paresis causes an ocular deviation in
      abduction; the image being perceived deviated contralaterally to the left. Thus,
      in our case, the neglect of the left image is equivalent to a right monocular
      functional blindness. However, bell cancellation test clearly worsened when
      assessed in left monocular vision confirming that eye patching can worsen
      attentional visual neglect. In conclusion, our case argues for the possibility of
      a functional monocular blindness induced by visual neglect. We think that in
      presence of strabismus, absence of diplopia should induce the search for
      hemispatial visual neglect when supratentorial lesions are suspected.

PMID- 15742608
TI  - Ankylosing spondylitis and multiple sclerosis in an HLA-B27 negative patient.
AB  - A 41-year-old man presented with vertigo and gait disturbance. He gave a 10-year
      history of definite ankylosing spondylitis with low back pain, limitation of
      spinal mobility, decreased chest expansion and radiological evidence of bilateral
      sacroiliitis. The vertigo attacks started 3 years before and he had insidious
      evolution of bilateral leg weakness, increased muscle tension and walking
      disability during the past 2 years. The HLA haplotypes of the patient were A2,
      A33, B14, B49, Bw4, Bw6, Cw7 and he was HLA-B27 negative. The axial and sagittal
      cranial magnetic resonance imaging (MRI) showed multiple foci of increased signal
      intensity in the periventricular white matter and cerebellar hemispheres,
      suggesting a demyelinating disease process. The MRI of the spine showed
      centromedullar high intensity lesions at C7, Th7-8, Th9-10 levels. The diagnosis
      was definite MS (primary progressive MS) as the patient had insidious
      neurological progression, CSF evidence of inthrathecal production of oligoclonal
      bands, conduction defects at VEP, multiple brain and additional spinal cord
      lesions on MRI and continued progression for more than 1 year.

PMID- 15742609
TI  - Masked deficit of vitamin B12 in the patient with heterozygous beta-thalassemia
      and spastic paraparesis.
AB  - The spinal cord, brain, optic nerves and peripheral nerves may be affected by
      vitamin B12 (cobalamin) deficiency. Deficiency of vitamin B12 also causes
      megaloblastic anaemia, meaning that the red blood cells are usually larger than
      normal. In this paper we report a 16-year old girl who was referred to us for the
      evaluation of mild paraparesis and paresthesias marked by tingling "pins and
      needles" feelings and general weakness. The patient, her parents and sisters were
      on a strict vegan diet, which made us believe that vitamin B12 deficiency may be
      the possible cause of the neurologic clinical manifestations. The serum level of
      vitamin B12 was low, but there was no macrocytosis in the routine blood
      examination. The electrophoresis of haemoglobin was pathologic, there was 3.7% of
      HbA2 and 11.6% of HbF (heterozygous form of beta-thalassaemia). When
      megaloblastic anaemia occurs in combination with a condition that gives rise to
      microcytic anaemia, many megaloblastic features may be masked. Instead of being
      macrocytic, the anaemia could be normocytic or even microcytic. Vitamin B12
      deficiency is a diagnosis that must not be overlooked. This case report turns the
      light on the fact that increased MCV is a hallmark in vitamin B12 deficiency, but
      it is not an obligatory sign.

PMID- 15742610
TI  - [Stress management among hospital nurses--stress & stress-coping scale (SSCQ) as
      applied to nurses].
AB  - The purpose of this study was to evaluate the validity of the Stress and Stress
      Coping Questionnaire (SSCQ) for female nursing groups. Subjects were 300 female
      nurses employed at hospitals. Mean age was 32.9 +/- 8.9 yr and mean number of
      years of work experience was 11.9 +/- 8.0 yr. Data for the study were collected
      via the self-completed SSCQ, which all subjects completed. In order to asses the
      validity of the SSCQ, subjects were also asked to complete a 60-question General
      Health Questionnaire (GHQ) that assessed mental well being. Based on the results
      of factor analysis, the original version of the SSCQ, comprising 153 questions in
      10 subscales, was revised to the nurse-specific SSCQ-N, comprising 123 questions
      and 15 subscales. Cronbach's alpha coefficient for subscales varied from 0.70 to
      0.83, showing a significant correlation with the point score of the GHQ, for
      demonstrating criterion-related validity in the SSCQ. These results verify the
      usefulness for female nursing groups of the SSCQ for assessing mental well being
      and suggesting ways to manage stress in nurses.

PMID- 15742611
TI  - [Development of a checklist for evaluation of mental health activities at the
      workplace].
AB  - "The Checklist for Evaluation of Mental Health Activities at the Workplace" was
      developed for workplace staff evaluating mental health activities in their own
      workplace. The validity and reliability of the checklist were examined and
      criteria for evaluation were developed for workplace/organization/companies with
      50 or more employees in Japan. The checklist initially included 33 items covering
      seven major domains of occupational mental health, with a four-point response
      option, based on the Japanese Guideline for Worker Mental Health in the Workplace
      and a relevant literature review. A questionnaire was send to 60 members of the
      Occupational Mental Health Committee (OMHC) of the Japan Society for Occupational
      Health to ask their opinions on the checklist and on the minimum requirement for
      each item on the checklist; 30 (50%) responded. A random sample of 1,335
      workplaces from a contractor list of workplaces for worker compensation insurance
      and a questionnaire was send to the personnel department to fill in the
      checklist; 412 (31.5%) responded and data from 335 of them with 50 or more
      employees were analyzed. Some OMHC members felt that one of the items (concerning
      the Total Health Promotion program) should be dropped; thus the checklist was
      revised to include 32 items, still covering the seven domains. Based on the
      workplace survey data, most domain scales showed internal consistency reliability
      at an acceptable level; explanatory factor analysis yielded a four-factor
      structure that was well concordant with the hypnotized seven-domain structure.
      Three levels of adequacy of mental health activities were set for each domain
      scale: "red" (inadequate), "yellow" (minimal), and "green" (adequate). One third
      of occupational health professionals from 49 workplaces rated the evaluation
      result based on the checklist as concordant with their view; 95% of them said the
      checklist would be useful in promoting occupational mental health activities. The
      study indicated that the checklist had reliability (based on internal consistency
      reliability) and content- and construct-validity (based on expert opinions, a
      factor-structure concordant with empirical data, and evaluation by workplace
      staff). The checklist seems useful in promoting occupational mental health
      activities.

PMID- 15742612
TI  - [A study in cases of Brugada-type electrocardiogram and its management proposals
      in health examination].
AB  - In 1992, Brugada et al. reported a characteristic electrocardiogram (ECG) pattern
      and ST-segment elevation in leads V1 to V3 associated with sudden death in
      patients without demonstrable structural heart disease. That disease is now
      called Brugada Syndrome. The diagnostic criteria for the Brugada Syndrome have
      still not been decided on, and the prevalence of Brugada type ECG (B-ECG) varies
      widely in Japan. Therefore, we should consider B-ECG according to the consensus
      statement from the European Society of Cardiology and we proposed its management
      in health examinations. There were 35 B-ECG cases (0.9%), all male out of 3,875
      Postal Service Trainees. There were 5 cases of Type I (Coved) (0.13%), 21 cases
      of Type II (0.54%), and 9 cases of Type III (0.23%), Only one case (0.026%) of
      Brugada Syndrome was found, and eventually, he received an Implantable
      Cardioverter Defibrillator (ICD). Type I (Coved) may be a more important
      electrocardiographic factor having a stronger causal relation to Ventricular
      Arrhythmia. Therefore, in management of health examinations, Type I patients with
      syncope or a family history of sudden cardiac death should visit a cardiologist
      for ICD-implantation, and even without any cardiac symptoms (syncope and a family
      history of sudden death), they are advised to visit a cardiologist for a program
      electrical stimulation (PES). Type II and III patients with any cardiac symptoms
      are advised to visit a cardiologist for PES or a drug challenge.

PMID- 15742613
TI  - [Skin symptoms developed among agricultural workers bitten by introduced
      biological control agents (Heteroptera) while cultivating green pepper in plastic
      greenhouses].

PMID- 15742614
TI  - Vaccinology--an historical review.

PMID- 15742615
TI  - Veterinary vaccines for animal and public health.
AB  - Vaccination is without doubt the most useful single measure available to prevent
      animal infectious diseases. The advantages of vaccination are numerous. It is the
      only available method to prevent, or sometimes cure, viral animal infections in
      the absence of broad spectrum antivirals and avoids the alternative of mass
      slaughtering of livestock. Antibiotic or anthelmintic resistance, and the problem
      of pharmaceutical residues, promote the use of vaccines rather than chemotherapy.
      Vaccines are environmentally friendly and increase animal welfare by preventing
      suffering from disease resulting from treatment for a cure which may result in
      antibiotic resistance and pharmaceutical residues in food. For the management of
      livestock health vaccines are the best tool to achieve sustainability. Veterinary
      vaccines cannot only be used to protect animal health but also human health from
      zoonotic infections through animal vaccination as exemplified by wildlife
      vaccination against rabies. In animal health the focus is now on animal
      infections rather than on animal diseases. Vaccines should be designed to prevent
      infection rather than to prevent clinical signs of disease and should, wherever
      possible, produce sterile immunity. Available technologies allow us to design
      "marker" vaccines together with their companion diagnostic tests which permit the
      distinction between vaccinated and infected animals even if the latter were
      previously vaccinated. Examples will be given of foot-and-mouth disease,
      classical swine fever, and herpesvirus infections of livestock such as
      pseudorabies or infectious bovine rhinotracheitis where carrier state or latency
      remain an issue after vaccination.

PMID- 15742616
TI  - The use of vaccines in South American foot-and-mouth disease eradication
      programmes.
AB  - Since the beginning of organized campaigns in the 1960s, vaccination has been a
      major component of national FMD control and eradication programmes in South
      America. Aqueous vaccines were used in the 1960s and 1970s, and the introduction
      of oil vaccines in the mid 1980s helped to decrease endemism. Bi- and trivalent
      FMD vaccine production increased from 266 thousand doses in 1967 to 580 million
      doses in 2002. Currently, over 200 million cattle are vaccinated twice yearly
      throughout the continent. This massive vaccination programme, along with outbreak
      and animal movement control, helped eradicate FMD in sizeable areas in the 1990s.
      Outbreaks in the Southern Cone during 2000/2001 were curbed mostly by repeated
      massive vaccination of cattle. The Hemispheric FMD Eradication Plan, with its end
      date of 2009, relies on cyclic vaccinations as a major instrument. Vaccination as
      the major component will continue until when?

PMID- 15742617
TI  - Foot-and-Mouth disease control using vaccination: the Dutch experience in 2001.
AB  - A first case of foot-and-mouth disease (FMD) was confirmed on a farm in Oene on
      21 March 2001. The Dutch eradication strategy for the area which is densely
      populated with susceptible animals was immediately applied: stamping out the
      infected herd and pre-emptive culling of all susceptible animals on farms within
      a radius of 1 km around an infected farm. If the organisation was unable to cull
      infected herds within 24 hours after detection and the neighbouring farms within
      four days, emergency ring vaccination would be applied. By 26 March it was clear
      that capacity problems prevented the required rapid culling and therefore the
      decision to apply emergency vaccination was taken. On 28 March vaccination of all
      susceptible animals was started in 2 km zones around infected farms. In the area
      where the first outbreak occurred, by 1 April 11 farms were found to be infected.
      Tracing the links between these infections was difficult, the farms being at a
      greater distance than 4 km from each other and fear increased that the disease
      could not be contained in this area. It was therefore decided to vaccinate a
      larger area: "Vaccination area Noord Veluwe". Suppressive vaccination was chosen.
      This implied that all vaccinated animals should be killed and destroyed.
      Vaccination rapidly reduced the number of new infections. In total 26 farms
      became infected with FMD. The last affected farm was confirmed on 22 April 2001.
      The last vaccinated animal was culled on 25 May 2001. EU rules also gave the
      option of choosing protective vaccination. The consequence was that only
      vaccinated cattle could stay alive. The status 'FMD-free without vaccination'
      however would then be recovered 12 months after the last outbreak. This
      consequence was too damaging to the export interests of the country. The killing
      of healthy vaccinated animals became the predominant factor in the discussion of
      farmers, politicians and the general public. The need for adjustments in the FMD
      eradication strategy and in the OIE and EU rules concerning FMD was strongly
      expressed in the International FMD Conference held in Brussels in December 2001.
      Since then these rules have been changed and as a result of this a more animal
      friendly eradication of FMD is now possible.

PMID- 15742618
TI  - Foot-and-mouth disease control using vaccination: South African experience.
AB  - South Africa has zoned status from the Office International des Epizooties (OIE)
      with the largest part of the country being foot-and-mouth disease (FMD)-free
      without vaccination. Outbreaks in this zone are handled differently from
      outbreaks in the control zones, which do not affect the export status of the
      country. However, the different socio-economic groupings need to be considered
      when reaching control decisions and in this regard, the country has been
      challenged with unique foot-and-mouth disease (FMD) control options. Vaccination
      has been shown to be effective both in ensuring that disease does not spread from
      the endemic to the free zone, as well as controlling outbreaks in the free zone.
      New adjuvants that claim to illicit longer lasting immunity have been tested with
      antigens derived from the SAT serotypes and animals were challenged one year post
      vaccination to determine the level of protection. However, even with vaccines
      that provide immunity for more than a year, an annual vaccination campaign will
      most probably not be acceptable in the buffer zone where calving occurs
      throughout the year.

PMID- 15742619
TI  - Vaccination as a control measure during the outbreak of foot-and-mouth disease in
      2000 in Korea.
AB  - The Republic of Korea had been free from foot-and-mouth disease (FMD) for 66
      years until 15 cases were confirmed between 24 March and 15 April in 2000. The
      FMD virus isolated in Korea was an O Pan Asia type, which was also responsible
      for the recent outbreaks in Japan and the U.K. Control measures including the
      stamping-out of infected animals on neighbouring farms, movement restrictions and
      emergency vaccination were implemented. The decision to vaccinate was made
      because the cattle affected were showing severe FMD lesions, there was
      significant possibility that a large amount of virus had already been shed and
      conditions at the time seemed to favour wind-borne spread. Also, because the
      spread was limited to cattle, it was assumed that the use of vaccinations would
      be more effective than if pigs had been affected. All susceptible animals within
      10 km radius of the infected farms were vaccinated with inactivated, double-oil
      emulsion vaccines. Totals of 860,700 and 661,770 animals were vaccinated during
      the first and second round of booster vaccinations, and were completed within
      five months of the first outbreak. The government decided to adopt a let-live
      policy so that the vaccinated animals were not slaughtered. However, they were
      placed under movement restrictions and had to be identified and registered.
      Although there were concerns about the vaccinated animals becoming carriers,
      extensive serological surveillance using NSP ELISA found no evidence of FMD in
      the remaining vaccinated population. The use of emergency vaccinations in 2000 is
      regarded as being a major factor in limiting the spread of FMD and containing the
      outbreak within a month.

PMID- 15742620
TI  - Experience with eradicating rinderpest by vaccination.
AB  - Rinderpest was such a devastating disease throughout Africa, Asia and Europe,
      capable of shaping the destinies of governments as well as the livelihoods of
      producers and consumers alike, that all sectors of society demanded that
      scientists should strive to develop a means of protecting cattle against the
      constant risk. The history of vaccination as a tool for the control of rinderpest
      is a long one but finally spawned a vaccine which certainly ranks highly among
      the safest and most efficacious of vaccines. Having this Tissue Culture
      Rinderpest Vaccine (TCRV) available generated aspirations of global rinderpest
      control and even eradication, which could now be considered feasible.

PMID- 15742621
TI  - Vaccination for the control of peste des petits ruminants.

PMID- 15742622
TI  - Contagious bovine pleuropneumonia vaccines and control strategies: recent data.
AB  - Contagious bovine pleuropneumonia is one of the most threatening transboundary
      cattle disease in Africa. However, with the exception of Botswana, very few
      African countries were able to implement eradication strategies for this disease,
      after it had recently re-infected a number of countries. Previous experimental
      studies have shown that emergency vaccination campaigns, based on a single
      injection, were not inducing a sufficient protection level to prevent further
      spread of the disease. In addition, post-vaccinal reactions were sometimes
      reported in the field when using vaccine strain T1/44, leading cattle owners to
      refuse the vaccination. On the contrary, antibiotics are used quite often in the
      field but there are insufficient data to assess their efficacy properly.
      Therefore experimental studies were implemented: (i) to check if higher dosages
      of the vaccine would be able to induce higher protection rates and (ii) to
      elucidate the origin of the post-vaccinal reactions observed with T1/44 and (iii)
      to gain preliminary results on the efficacy of long-acting tetracycline. The
      first experiment included the use of three doses of vaccine strains T1/44 and
      T1sr: 10(7), 10(8) and 10(9) mycoplasmas per dose. T1/44 seemed to induce a
      higher protection (70%) than T1sr (60%). However, there was no observable dose
      effect for these vaccine strains. The second experiment was performed by
      injecting various MmmSC strains subcutaneously into susceptible cattle. One of
      these strains was an isolate obtained from a "Willems" reaction following a
      vaccination with T1/44. This isolate, called T1B, induced typical invading oedema
      at the injection site in a similar way to the pathogenic strain, whereas the
      original T1/44 vaccine strain did not. These findings indicate that the strain
      has reverted to virulence. Finally the antibiotic trials showed that long-acting
      tetracycline was able to reduce the losses due to the disease but could not
      prevent the persistence of viable MmmSC in treated animals. The consequences of
      these findings are discussed. They reinforce the need for additional research on
      new vaccines able to elicit longer lasting protection. However, once continuing
      additional field research is obtained, it should allow better defined strategies
      to be put in place. Meanwhile, immediate action should be taken to prevent the
      further spread of CBPP in the Southern part of Africa.

PMID- 15742623
TI  - Vaccination in the control strategy of bluetongue in Italy.
AB  - The incursion of bluetongue (BT) in Italy, in August 2000, caused heavy economic
      losses, partly due to the direct effect of the disease on the animals, but mostly
      due to indirect losses due to ruminant movement restrictions conducive to heavy
      losses to the cattle and sheep industry. To limit losses due to both disease and
      virus circulation, which was the cause of movement restrictions, the Italian
      Ministry of Health in May 2001 ordered the vaccination of animals of all domestic
      ruminant species in infected and "at risk" areas. The vaccination strategy
      derived from a risk assessment that suggested that the vaccination of all
      domestic ruminants could reduce both direct losses and virus circulation
      significantly. The different levels of vaccination coverage, achieved in the
      various regions of Italy, had clear consequences on the spread of both disease
      and infection. In regions where more than 80% of the target populations were
      vaccinated properly, the disease disappeared almost completely and virus
      circulation was significantly reduced, as documented by the serological
      surveillance system, after a single vaccination cycle. This led to a significant
      decrease in the areas subject to movement restrictions. Data generated by both
      field and controlled experiments contributed to modify the EU approach to BT and
      to some of the conclusions of the Third OIE International Symposium on Bluetongue
      that will probably lead to a modification of the Office International des
      Epizooties (OIE) standard.

PMID- 15742624
TI  - Animal coronavirus vaccines: lessons for SARS.
AB  - Severe acute respiratory syndrome (SARS) emerged in China and spread globally as
      a human pandemic. It is caused by a new coronavirus (CoV) of suspect animal
      origin. The emergence of SARS stunned medical scientists, but veterinary
      virologists had previously recognized CoVs as causing fatal respiratory or
      enteric disease in animals with interspecies transmission and wildlife
      reservoirs. Because of its public health impact, major efforts are focused on
      development of SARS vaccines. Occurrence of CoV disease at mucosal surfaces
      necessitates the stimulation of local immunity, having an impact on the vaccine
      type, delivery and adjuvant needed to achieve mucosal immunity. Such immunity is
      often short-lived, requires frequent boosting and may not prevent re-infection,
      all factors complicating CoV vaccine design. SARS vaccine efforts should be
      enhanced by understanding the correlates of protection and reasons for the
      success or failure of animal CoV vaccines. This review will focus on studies of
      immunity and protection in swine to the enteric CoV, transmissible
      gastroenteritis (TGEV) versus the respiratory variant, porcine respiratory CoV
      (PRCV), comparing live, inactivated and subunit vaccines, various vaccine
      vectors, routes and adjuvants. In addition avian infectious bronchitis CoV (IBV)
      vaccines targeted for protection of the upper respiratory tract of chickens are
      discussed. Unfortunately, despite long-term efforts, effective vaccines to
      prevent enteric CoV infections remain elusive, and generally live, but not killed
      vaccines, have induced the most consistent protection against animal CoVs.
      Confirmation of the pathogenesis of SARS in humans or animals models that mimic
      SARS may further aid in vaccine design and evaluation.

PMID- 15742625
TI  - Control of infectious bursal disease virus by vaccination.
AB  - In summary, the currently used conventional vaccines are used effectively to
      control the disease. The promise of the new generation of vaccines has not
      materialized yet. This is partly due to the incomplete understanding of the
      molecular basis of immunogenicity resulting in an inadequate immune response. It
      should be emphasized that RNA viruses such as IBDV are prone to change through a
      variety of mechanisms. This requires vigilance in monitoring field viruses and
      the natural history of the disease.

PMID- 15742626
TI  - Successful control of Marek's disease by vaccination.
AB  - Marek's disease (MD) is a neoplastic disease of poultry caused by the highly
      contagious Marek's disease virus (MDV). Vaccination with live attenuated vaccines
      forms the cornerstone of the current MD control programmes. The widespread use of
      the vaccines in the last 30 years has significantly reduced the losses from MD.
      Despite the huge success of the vaccination policy, the continuing trend in
      virulence increase of field strains of MDV has forced the introduction of new
      generations of vaccines to keep up with the creeping virulence increase of MDV.
      In these circumstances, it is very important to undertake research to develop
      more sustainable strategies of control. Development of new recombinant DNA
      technologies such as the use of bacterial artificial chromosomes (BAC) offers the
      possibility of developing molecularly-defined vaccines. In addition, the
      availability of the whole chicken genome sequence allows the opportunity of
      exploiting genetic resistance against MD as another sustainable strategy.

PMID- 15742627
TI  - Field experiences in the control of avian influenza outbreaks in densely
      populated poultry areas.
AB  - From 1997 to 2003, Italy has been affected by two epidemics of highly pathogenic
      avian influenza (HPAI) and by several outbreaks of low pathogenic avian influenza
      (LPAI). In 1999-2000 a severe HPAI epidemic affected the country, causing 413
      outbreaks: a total of about 16 million birds died or were stamped out. From
      August 2000 to March 2001, a H7N1 LPAI strain infected 78 poultry farms. The last
      affected flock was stamped out on the 26th of March 2001. In October 2002,
      another LPAI virus of the H7N3 subtype emerged and infected a total of 388
      poultry holdings. Eradication measures were based on stamping out or controlled
      marketing of slaughtered birds on infected farms and on the prohibition of
      restocking. Restriction measures on the movement of live poultry, vehicles and
      staff were also imposed. To supplement these disease control measures, two
      emergency vaccination programmes, based on the "DIVA" (Differentiating Infected
      from Vaccinated Animals) strategy were implemented. The two vaccination campaigns
      (2000-2002 and 2002-2003) both resulted in the eradication of infection. However,
      the first campaign appeared to be more successful that the second and possible
      explanations are discussed.

PMID- 15742628
TI  - Control of Newcastle disease by vaccination.
AB  - Vaccination for Newcastle disease (ND) is routinely practised in countries where
      virulent strains of the Newcastle disease virus (NDV) are endemic and in
      countries where virulent strains do not exist but ill-timed infection by a low
      virulent field strain may have significant economic consequences for the
      producer. The types of vaccines and vaccination schedules used vary depending on
      the potential threat, virulence of the field challenge virus, type of production,
      and production schedules. A combination of live and inactivated ND vaccine,
      administered simultaneously, is shown to provide better protection against
      virulent NDV and has been successfully used in control programmes in areas of
      intense poultry production. A potential limiting factor in the use of live
      vaccines to control virulent ND is that live virus can interfere with
      surveillance and laboratory diagnosis. However, a new assay, the real-time
      reverse transcriptase-polymerase chain reaction (RRT-PCR), differentiates low
      virulent from virulent NDV, thus minimizing the disadvantage of live virus
      vaccines in the face of an outbreak and may facilitate the use of such vaccines
      to control outbreaks of virulent ND in the future.

PMID- 15742629
TI  - Oral vaccination of wildlife against rabies: opportunities and challenges in
      prevention and control.
AB  - Rabies is an acute, progressive, fatal encephalitis caused by viruses in the
      Family Rhabdoviridae, Genus Lyssavirus. Rabies virus is the representative member
      of the group. Warm-blooded vertebrates are susceptible to experimental infection,
      but major primary hosts for disease perpetuation encompass bats and mammalian
      carnivores. The dog is the global reservoir, and important wild carnivores
      include foxes, raccoons, skunks, and mongoose, among others. Traditionally,
      reliance upon long-term, widespread, government-supported programmes aimed at
      population reduction of animals at risk has been unsuccessful as the sole means
      of rabies control, based in part upon economical, ecological and ethical grounds.
      In contrast, immunization of domestic dogs with traditional veterinary vaccines
      by the parenteral route led to the virtual extinction of canine-transmitted
      rabies in developed countries. Taken from this basic concept of applied herd
      immunity, the idea of wildlife vaccination was conceived during the 1960s, and
      modified-live rabies viruses were used for the experimental oral vaccination of
      carnivores by the 1970s. The development of safe and effective rabies virus
      vaccines applied in attractive baits resulted in the first field trials in
      Switzerland in 1978. Thereafter, technical improvements occurred in vaccine
      quality and production, including the design of recombinant viruses, as well as
      in the ease of mass distribution of millions of edible baits over large
      geographical areas. Over the past few decades, extensive oral vaccination
      programmes focusing upon the red fox, using hand and aerial distribution of
      vaccine-laden baits, have resulted in the virtual disappearance of rabies in
      Western Europe. The same dramatic observation held true for southern Ontario.
      During the 1990s in the United States, oral vaccination programmes concentrated
      upon raccoons, grey foxes, and coyotes, with similar success. For example,
      raccoon rabies has not spread west of the current focus in the eastern states,
      grey fox rabies is contained in west central Texas, and no recent cases of rabies
      have been reported from coyotes away from the Mexican border for several years.
      Despite the progress observed and the absence of substantive adverse
      environmental or health effects, oral vaccination is not a panacea, and should be
      viewed as an important adjunct to traditional prevention and control techniques
      in human and veterinary medicine. Local outbreak suppression of rabies among free
      ranging wildlife is documented, and regional elimination of particular virus
      variants among specific, targeted carnivore hosts is demonstrable, but true
      disease eradication is not achievable at the present time by current techniques.
      For example, no practical vaccination methods have been designed for bats.
      Although lyssaviruses appear in relative compartmentalization between the
      Chiroptera and Carnivora, major spillover events have been detected from bats to
      carnivores, and phylogenetic analyses suggest a historical basis for extant viral
      origins due to interactions between these taxa. Thus, bio-political
      considerations aside, the possibility for pathogen emergence resulting from
      transmission by rabid bats with subsequent perpetuation among other animals
      cannot be discounted easily on any continent, with the possible exception of
      Antarctica. Clearly, given their biodiversity, distribution, and abundance, novel
      methods would be necessary to consider meaningful control of rabies in these
      unique volant mammals. Newer approaches in biotechnology may be envisaged some
      day for eventual extension to bats, as well as more widespread application to
      global canine rabies remediation in developing countries.

PMID- 15742630
TI  - Perspectives for rabies control and eradication from domestic species in
      developing countries.

PMID- 15742631
TI  - The Pan American Health Organization (PAHO) role in the control of rabies in
      Latin America.

PMID- 15742632
TI  - Application of new vaccine technologies for the control of transboundary
      diseases.
AB  - Vaccines have played an important role in the control of diseases of livestock
      and poultry, including Transboundary Diseases. In the future, vaccines will play
      a greater role in controlling these diseases. Historically, inactivated whole
      viruses in various adjuvant systems have been used and will continue to be used
      in the near future. For the future, emerging technologies will allow targeted use
      of only the protective antigens of the pathogen and will provide the opportunity
      for differentiating between vaccinated and field-exposed animals. Furthermore,
      the expression of cytokines by vaccines will afford earlier or greater
      enhancement of protection than can be achieved by the protective response
      elicited by the antigenic epitopes of the pathogen alone. Avian influenza (AI) is
      a good case for studying future trends in vaccine design and use. Inactivated AI
      virus (AIV) vaccines will continue as the primary vaccines used over the next 10
      years. These vaccines will use homologous haemagglutinin sub-types, either from
      the use of field strains or the generation of new strains through the use of
      infectious clones produced in the laboratory. The latter will allow creation of
      high growth reassortants, which will provide consistent high yields of antigen
      and result in potent vaccines. New viral and bacterial vectors with inserts of
      AIV haemagglutinin gene will be developed and potentially used in the field. Such
      new vectors will include herpesvirus-turkey, infectious laryngotracheitis virus,
      adenoviruses, various types of paramyxoviruses and Salmonella sp. In addition,
      there is a theoretical possibility of gene-deleted mutants that would allow the
      use of live AIV vaccines, but the application of such vaccines has inherent
      dangers for gene reassortment with field viruses in the generation of disease
      causing strains. Subunit haemagglutinin protein and DNA haemagglutinin gene
      vaccines are possible, but with current technologies, the cost is prohibitive. In
      the future, effective AI vaccines must prevent clinical signs and death, increase
      resistance of the host to infection, decrease the rate of replication and
      shedding of a challenge or field virus and provide uniform protection following
      single immunization. Mass application technologies of new virus or bacterial
      vector systems will provide economic incentives for adoption over current labour
      intensive manual individual bird injection methods used with today's AI vaccines.

PMID- 15742633
TI  - DIVA--a vaccination strategy enabling the detection of field exposure to avian
      influenza.
AB  - The present paper reports on the development, validation and field application of
      a control strategy for avian influenza infections in poultry. The "DIVA"
      (Differentiating Infected from Vaccinated Animals) strategy is based on the use
      of an inactivated oil emulsion vaccine containing the same haemagglutinin (H)
      subtype as the challenge virus, but a different neuraminidase (N). The
      possibility of using the heterologous N subtype, to differentiate between
      vaccinated and naturally infected birds, was investigated through the development
      of an "ad hoc" serological test based on the detection of specific anti-N
      antibodies. This test is based on an indirect fluorescent antibody assay, using
      as an antigen a baculovirus expressing recombinant N proteins. The vaccination
      strategy has been tested in the laboratory and shown to be efficacious both
      against challenge with highly pathogenic AI viruses and with low pathogenicity AI
      viruses, ensuring clinical protection, reduction of duration and titre of
      shedding. In addition, vaccination resulted in an increased resistance to
      infection. The companion diagnostic tests directed to the detection of anti-N1
      and anti-N3 antibodies have been validated in the laboratory and using field
      samples. The serological assay showed an "almost perfect agreement" (Kappa value)
      with the HI test, with relative sensitivity and specificity values of 98.1 and
      95.7, respectively. The results of the present investigation suggest that the
      "DIVA" control strategy may represent a tool to support the eradication of avian
      influenza infections in poultry.

PMID- 15742634
TI  - Development of new concepts in vaccines and their effects on the control of
      infectious diseases (classical swine fever in particular).
AB  - Molecular biology and technological advances in DNA recombination have ushered in
      a new era in vaccinology. In particular, "deleted" vaccines have emerged over the
      past 10 years. The first such vaccines were used to protect pigs against
      Aujeszky's disease. The same principles were subsequently applied to the
      development of vaccines against classical swine fever (CSF), relaunching the
      debate on whether to use sanitary or medical measures. The decision about the
      measures to be applied depends on several criteria and factors such as the
      capabilities of the vaccines to be used in an emergency situation and the local
      epidemiological situation. Under the light of the last CSF serious epizootic
      which appeared in Europe in 1997, the effects of the different types of measures
      are discussed.

PMID- 15742635
TI  - Aujeszky's disease vaccination and differentiation of vaccinated from infected
      pigs.
AB  - In this paper, the use of a glycoprotein E (gE)-deleted vaccine to eradicate
      Aujeszky's disease virus (ADV) or pseudorabies virus in swine is described. In
      regions where there is a dense population of swine, ADV is highly prevalent and
      intensive vaccination with such a marker vaccine has resulted, in several
      countries, in a decrease of the field virus prevalence to a sufficiently low
      level so that culling becomes economically feasible. The evolution in the
      reduction of circulating field virus can be followed at herd and/or population
      level by serological monitoring for antibodies against gE, using commercially
      available enzyme-linked immunosorbent assays. To be successful, other measures
      besides the vaccination in itself are important, such as the proper use and
      administration of the vaccine, repeated boosters, prevention of introduction of
      gE-positive animals and restriction in the movement of animals from gE-positive
      herds. When pockets of infection remain, intensifying the vaccination may be
      needed. Culling of remaining gE-positive animals, particularly breeders, is
      usually necessary. Some European Union (EU) member states have become ADV-free
      using this approach. Others are still working at it. The success is often
      dependent on whether or not a good discipline exists. The disease situation in
      the different EU member states is described. In ADV-free regions with dense swine
      populations at risk, it is advisable not to stop the vaccination too soon,
      particularly when the infection status in neighbouring countries or trade
      partners is not equally good.

PMID- 15742636
TI  - Control and eradication of African horse sickness with vaccine.
AB  - African horse sickness (AHS) is an infectious but no-contagious viral disease of
      equidae with high mortality in horses. The disease is caused by an arthropod
      borne double-stranded RNA virus within the genus Orbivirus of the family
      Reoviridae transmitted by at least two species of Culicoides. Nine different
      serotypes have been described. The nine serotypes of AHS have been described in
      eastern and southern Africa. Only AHS serotypes 9 and 4 have been found in West
      Africa from where they occasionally spread into countries surrounding the
      Mediterranean. Examples of outbreaks that have occurred outside Africa are: in
      the Middle East (1959-1963), in Spain (serotype 9, 1966, serotype 4, 1987-1990),
      and in Portugal (serotype 4, 1989) and Morocco (serotype 4, 1989-1991).
      Laboratory diagnosis of AHS is essential. Although the clinical signs and lesions
      are characteristic, they can be confused with those of other diseases. Several
      techniques have been adapted for the detection of RNA segments, antibodies and
      antigen. Two types of vaccines have been described for AHS virus. Attenuated live
      vaccines (monovalent and polyvalent) for use in horses, mules and donkeys, are
      currently available, as well as a monovalent, serotype 4, inactivated vaccine,
      produced commercially but no longer available. New vaccines, including a subunit
      vaccine, have been evaluated experimentally. In this paper a review of the last
      AHS outbreaks in Spain, occurring during 1987-1990, and affecting the central and
      south part of the country, is presented. The role that vaccination played for the
      control and eradication of the disease, as well as other aspects such as
      climatological conditions, number of vectors and horse management, are also
      presented and evaluated.

PMID- 15742637
TI  - Making a vaccinate-to-live policy a reality in foot-and-mouth disease.
AB  - Public opinion and the availability of new technologies are making the use of
      'stamping- out' an increasingly unattractive option as the method of first choice
      for foot-and-mouth disease (FMD) control in FMD-free countries or zones seeking
      to control incursion of disease. There is therefore increasing pressure to adopt
      a 'vaccinate-to-live' policy in these circumstances. For a successful vaccinate
      to-live policy, veterinary services need access to appropriate, licensed
      vaccines; to have adequate contingency plans to ensure that they can deliver the
      required vaccine, where and when it is needed; and to have developed an 'exit
      strategy' that enables recognition of freedom from disease as quickly as
      possible. This paper discusses progress towards these requirements and the
      problems that still need to be addressed before a vaccinate-to-live policy can
      become the option of first resort.

PMID- 15742638
TI  - Foot-and-Mouth disease 'vaccination-to-live': possibilities and constraints.
AB  - Major constraints to the adoption of a 'vaccination to live' policy during an
      outbreak of foot-and-mouth disease (FMD) in a previously FMD-free country are the
      dual problems in the development of persistent infection (>28 days) in some
      vaccinated ruminants exposed to virulent virus and reliably detecting these
      persistently infected animals. Rapid advances in immunology, virology, molecular
      biology and information management present significant opportunities for
      improving the management of FMD outbreaks using a variety of scientifically
      advanced tools without the need for slaughtering large numbers of animals. A more
      rapid return to FMD-free status should be capable of being achieved without
      massive slaughter of animals through: (i) improvements in vaccine efficacy, onset
      of immunity, and marker specificity; (ii) development of anti-viral compounds as
      an aid in the control of outbreaks with or without vaccination; (iii) improvement
      of rapid diagnostic tests to detect early infection and persistent infection
      accurately and (iv) the capture, validation and management of data on animal
      identification, vaccination and infection status, and movement. The most
      effective improvements will occur if all these strategies are used in
      combination.

PMID- 15742639
TI  - Vaccination: foot-and-mouth disease experience in South America.
AB  - Vaccination against foot-and-mouth disease (FMD) constitutes an important
      component of the policy for its control and eradication in South America.
      Considering that immunization may not impair subclinical infection, it became
      advisable to ally to vaccination campaigns a surveillance instrument to monitor
      silent viral circulation. Novel approaches for the evaluation of antibodies to
      FMD non-capsid proteins (NCPs), developed and validated at PANAFTOSA proved
      valuable for assessing viral circulation in immunized populations. The extensive
      and coordinated application in South America of vaccination together with this
      serosurvey tool indicated the effectiveness of systematic vaccination to prevent
      FMD spread and to restrain silent viral circulation intra- and inter- herds, and
      gave input to an old controversy related to the real epidemiological
      significance, if any, of carrier animals under the vaccination conditions in
      South America. The fitness of NCP tests to assess viral circulation in a
      population supported the incorporation into the OIE code of the "free of FMD with
      vaccination" category as a step prior to the recognition of the "free of FMD
      without vaccination" category. Likewise it released the path to allow animals,
      vaccinated for protective purposes during emergencies, to live for the term of
      their productive lives.

PMID- 15742640
TI  - The use of serology as part of the exit strategy to the 1996 epidemic of FMD in
      the Balkans.

PMID- 15742641
TI  - Australian contingency plans for emergency animal disease control: the role of
      antigen/vaccine banks.
AB  - Vaccination is an important element of contingency plans for many animal
      diseases. The decision whether or not to use vaccine is complex, and must
      consider epidemiological, economic and social issues. Vaccines are rarely
      available in a country for emergency animal diseases unless a low pathogenicity
      strain of the agent is present or it is localised in carrier hosts. High quality
      commercial vaccine from overseas is often the preferred source of vaccine in an
      emergency, although less reliable sources may be used with additional safeguards.
      Alternatively, master seeds may be imported or developed for production within
      the country For contingency planning, diseases may be ranked according to the
      expected role of vaccine in the disease eradication strategy, with diseases for
      which vaccine is part of the initial response strategy receiving highest priority
      for action. A range of preparedness options is available, ranging from
      identifying producers of vaccine, obtaining permits for import and use from
      regulatory authorities, to establishing vaccine or antigen banks. Countries need
      to consider their individual situations and develop strategies to address the
      diseases of significance to them.

PMID- 15742642
TI  - The use of antigen and vaccine banks in case of emergency vaccination in the
      European community.
AB  - The Community control measures for foot-and-mouth disease (FMD) have been
      reviewed and are currently laid down in Directive 2003/85/EC of 29 September
      2003. The Community is free of FMD and infection without practising vaccination.
      Legal provisions are in place to resort to emergency vaccination where required
      by the epidemiological situation and reserves of suitable antigens of the FMD
      virus for express formulation into vaccines have been established.

PMID- 15742643
TI  - A global virtual network for foot-and-mouth disease in case of emergency.
AB  - The use of emergency vaccination is considered in different contingency national
      plans as part of a foot-and-mouth disease (FMD) control strategy in countries
      whether vaccination is practised or not. The development of the inter
      governmental and national FMD vaccine and antigen banks and some technical and
      operational problems that could affect their efficiency are analysed. The
      possibility of improving and implementing a more rational use of the antigen and
      vaccine banks through the creation of a Global Virtual Network of Vaccine and
      Antigen Banks is discussed.

PMID- 15742644
TI  - Extending the foot-and-mouth disease module to the control of other diseases.
AB  - During the recent devastating epidemics of foot-and-mouth disease (FMD),
      bluetongue (BT), the highly pathogenic avian influenza (HPAI) and New Castle
      disease, more than 115 million animals were culled. The mass slaughter of animals
      raised serious ethical questions. These epidemics showed that the use of
      emergency vaccination is an essential element in disease control. During the last
      decade the FMD antigen banks have proved to be effective and this module should
      be extended. An international vaccine stock should be considered for classical
      swine fever and HPAI. Agreements with vaccine producers should be made easily
      available, with instant access to a vaccine reserve for rinderpest, peste des
      petits ruminants, BT, African horse sickness and Rift valley fever. These
      vaccines should meet international standards and should allow distinction between
      vaccinated and infected animals. Information should be gathered proactively on
      the use of vaccines for lumpy skin disease, sheep and goat pox and contagious
      bovine pleuropneumonia.

PMID- 15742645
TI  - Vaccination against salmonella, enterohaemorrhagic E. coli and Campylobacter in
      food-producing animals.
AB  - The threat of zoonotic infection with food-poisoning enteric pathogens remains a
      major threat to public health throughout the world. Control of enteric pathogens
      within food-producing animals remains an obvious strategy to prevent the
      introduction of these pathogens into the human food chain. Vaccines are currently
      available for the control of Salmonella; however such vaccines vary in their
      efficacy and acceptability to the food production industries and consumers.
      Vaccines for the control of enterohaemorrhagic E. coli and Campylobacter are
      currently unavailable. Understanding the molecular basis of how these organisms
      colonise the intestines and cause disease is essential for the development of
      effective multivalent vaccines. The mechanisms by which these organisms colonise
      the gut will be reviewed. Bacterial Type Three Secretion Systems (TTSS) have been
      shown to be major virulence factors influencing the colonisation and
      pathogenicity of Salmonella and enterohaemorrhagic E. coli in some but not all
      animal species. Thus, understanding the specific nature of host/pathogen
      interactions is crucial in the development of cross-species vaccines. TTSSs act
      by delivering effector proteins into intestinal epithelial cells, which act to
      modify signalling events in host cells causing cytoskeletal and
      pathophysiological changes to the benefit of the pathogen. Disruption of TTSSs
      and/or related secreted effector proteins can be adopted as a strategy for the
      attenuation of live vaccine strains. Furthermore secreted effector proteins have
      the potential to be incorporated into sub-unit vaccines. As many of such effector
      proteins are conserved between different serotypes, such vaccines offer the hope
      of cross-serotype protective immune responses. Novel experimental vaccines are
      currently being developed to exploit these and other recent discoveries in
      bacterial virulence mechanisms. The potential of such vaccines to control
      zoonotic pathogens will be discussed.

PMID- 15742646
TI  - Potential use of vaccination in cattle or badgers to control bovine tuberculosis.
AB  - The application of regular herd testing to identify and remove infected animals
      has proved to be a highly successful method of controlling bovine tuberculosis
      (TB) in many parts of the world. However, in some countries, notably the United
      Kingdom, Ireland and New Zealand, the disease has continued to pose a significant
      problem, despite intensive herd testing. Persistence of disease in these
      countries is associated with the presence of wildlife reservoirs of infection.
      Attempts to control bovine TB by culling of wildlife have been, at best, only
      partially successful and have proved difficult to sustain. This has led to
      considering of vaccination either of wildlife or cattle as a potential control
      measure. However, there are a number of obstacles that need to be overcome before
      vaccination can be considered a practical option. Vaccine efficacy, methods used
      for vaccine delivery in wildlife, potential interference of vaccination with
      diagnostic tests for cattle and appropriate design of field trials are among the
      issues that need to be addressed.

PMID- 15742648
TI  - The role of VICH (Veterinary International Cooperation on Harmonisation).

PMID- 15742647
TI  - Vaccination for the prevention of cysticercosis.
AB  - Several species of taeniid cestode parasites cause cysticercosis in their
      intermediate hosts. The most important species is Taenia solium, which infects
      pigs as the natural animal intermediate host but also may infect humans as
      intermediate hosts, leading to the disease known as neurocysticercosis. T. solium
      has been identified as a potentially eradicable disease and increasing attention
      is being placed on efforts to control transmission of the parasite. One option to
      assist with control of the disease is to prevent infection occurring in pigs by
      vaccination, thereby breaking the parasite's life-cycle and removing the source
      of infection for humans. Several approaches are being examined towards
      development of vaccines against T. solium, one of which is the application of
      recombinant oncosphere antigens. Two different oncosphere antigens, designated
      TSOL18 and TSOL45, have been evaluated, each of which has been shown to induce
      complete or near complete protection against experimental challenge infection in
      four separate vaccine trials in pigs. Investigations have begun towards
      characterising various aspects of this vaccine before undertaking controlled
      field trials. The TSOL18/TSOL45 vaccine has the potential to make a substantial
      contribution to the control and, potentially, the eradication of human
      neurocysticercosis.

PMID- 15742649
TI  - The role of OIE in harmonization.
AB  - The OIE is active in international harmonization in the veterinary medical arena
      in a variety of ways. This paper will focus on OIE publications, the VICH,
      CAMEVET, and the role of collaborating centres.

PMID- 15742650
TI  - Harmonization of testing requirements for veterinary vaccines.

PMID- 15742651
TI  - Harmonising testing requirements for FMD vaccines.

PMID- 15742652
TI  - Integrated epidemiology and economics modelling for the management of animal
      health.
AB  - This paper discusses the role of integrated epidemiology and economics modelling
      in animal health planning, with particular reference to the evaluation of
      national level interventions that involve the vaccination of livestock. Well
      integrated epidemiology and economics is considered essential if model outputs
      are to be of value in national animal disease control planning. The different
      approaches to the use of modelling in priority setting and resource allocation in
      animal health are reviewed and discussed. The authors conclude that this
      particular application of modelling is poorly developed, due in part to the
      complexities involved. Much more has been done to develop models that evaluate
      the merits of different intervention scenarios for a given single disease, and
      examples of these are presented. However, the authors conclude that despite the
      widespread use of such models, there is still considerable scope for the
      development of a more standardised approach, incorporating consideration of both
      direct and indirect implications of intervention options. In discussing the
      changing demands on animal health economics modelling, the authors propose that
      increased attention should be given to the valuation of "externalities", the
      calculation and interpretation of the distribution of costs and benefits, the
      evaluation of the impact of disease control on poverty reduction, and the
      development of real-time economics modelling techniques, to assist particularly
      in the effective management of disease outbreaks.

PMID- 15742653
TI  - The control of foot-and-mouth disease in Botswana: special reference to
      vaccination.
AB  - Botswana has a history of Foot-and-Mouth Disease (FMD) occurrence and control
      that dates far back into the 1930s. Conditions in the southern African region are
      favourable for spiking FMD outbreaks due to Southern African Territories (SAT)
      serotypes, because of the co-existence of the agent, hosts and a conducive
      environment. In the past these parameters were less controlled and FMD outbreaks
      were common in the region, causing tremendous social and economic losses. The
      inception of conventional FMD vaccines in the region in the 1970s led to a
      significant improvement in the control of the disease. Vaccination used with
      other appropriate strategies has been the cornerstone of FMD control strategy in
      Botswana. FMD vaccine used in Botswana is manufactured locally; it is effective
      and has been responsible for the elimination of FMD outbreaks since the early
      eighties. FMD vaccination is a costly exercise. The programme has been sustained
      for decades because there is political will and financial support from
      government. However, its economic value can only be determined through a cost
      benefit analysis, which is not a subject of this paper. The experience of FMD
      control in Botswana, with special reference to vaccination, is discussed.

PMID- 15742654
TI  - Strategy for the control of foot-and-mouth disease in Uruguay.
AB  - FMD was diagnosed in Uruguay and in most of the South American countries in 1870.
      In 1961 the first law was issued to enforce the control of the disease. In 1990 a
      new regulation was approved which determined the process to eradicate FMD. The
      last clinical case was on June 18th 1990, and in 1996 the OIE declared Uruguay a
      free country without vaccination. In 2001 FMD was re-introduced, with an outbreak
      of 2057 animals which were controlled throughout four months of strong activity
      which ended with two vaccinations of all livestock. On May 22nd 2003, the OIE
      recognized Uruguay as a country 'free with vaccination'.

PMID- 15742655
TI  - Strategy for the control of foot-and-mouth disease in Southeast Asia (SEAFMD).
AB  - The OIE Southeast Asia Foot-and-Mouth Disease Campaign (SEAFMD) involves the
      coordinated control of foot-and-mouth disease by eight of the ASEAN countries. A
      long term vision for SEAFMD has been developed and the core element is a
      progressive zoning approach to the control and eradication of FMD in the region.
      This paper describes the current status of FMD in Southeast Asia and progress
      towards achievement of OIE free zone status for FMD in parts of the Philippines
      and Malaysia and the initiation of the Malaysia-Thailand-Myanmar (MTM) Peninsular
      Campaign for FMD Freedom. In mainland Southeast Asia, the progressive zoning
      approach involves several sub-regional groups working in parallel to oversee the
      epidemiological and economic studies required to determine the feasibility of the
      approach. Areas involved include the Lower Mekong Basin, Upper Mekong Basin,
      parts of Myanmar and the Red River Delta of Vietnam. The paper describes the
      current usage of vaccines for FMD in Southeast Asia and provides recommendations
      for their supply and use in the new regional initiatives.

PMID- 15742656
TI  - The role of the European Food Safety Aauthority (EFSA) on animal diseases.

PMID- 15742657
TI  - Successful applications of OIE standards in the prevention and control of
      infectious animal diseases.

PMID- 15742658
TI  - The importance of vaccination in the control and eradication of infectious animal
      diseases.

PMID- 15742659
TI  - Very fast (and safe) inactivation of foot-and-mouth disease virus and
      enteroviruses by a combination of binary ethyleneimine and formaldehyde.
AB  - For FMD vaccine production, inactivation of the FMD virus is the most critical
      step. Formerly, from 1940 onwards, the virus was inactivated with formaldehyde.
      This inactivation was relatively slow, about 0.2 - 0.3 log 10 per hour. Because
      formaldehyde not only reacts with the virus produced but with many other
      components in the medium, such as proteins and amino acids, its concentration can
      become rate-limiting and inactivation plots may show tailing-off, resulting in
      residual infectivity. Many of the bad stories of post-vaccination outbreaks date
      back to the use of formaldehyde-inactivated vaccines (e.g. the outbreaks in
      France in 1981 and in Eastern Germany causing the Danish outbreak in 1982). Much
      faster and safer inactivation was obtained with aziridines and in the 1980s
      binary ethyleneimine (BEI) was introduced in practically all vaccine production
      laboratories. If inactivation plots are made of every production batch, as is now
      required by the European Pharmacopoeia, and these plots show proper inactivation
      rates, vaccines can considered to be completely safe. Under optimal conditions,
      inactivation rates are in the range of 0.5 - 1.0 log 10 per hour. In general, the
      inactivation takes 40-48 hours,which will guarantee complete inactivation of all
      virus particles in a batch. Since formaldehyde (FA), the 'classical' inactivating
      agent, inactivates at a rate of 0.3 logs per hour only, a significant
      contribution of FA to the inactivation of BEI can hardly be expected. However,
      here it is shown that FA added during the BEI-inactivation process strongly
      augments inactivation rates with a hundred to thousand-times (to 2.5-3.5 logs per
      hour). This will enable inactivation during a working day or just overnight with
      even higher safety levels of the vaccines. Also, it is known that formaldehyde
      cross-links viral proteins which will stabilise the antigen. The short
      inactivation times will limit proteolytic destruction of 146 S antigen and
      increase antigen yields. It is expected that by the cross-linking activity of FA
      the stability of the antigen (and of vaccines) and the endurance of the immune
      response will be favourably influenced.

PMID- 15742660
TI  - The macro-economic impact of a foot-and-mouth disease incursion in New Zealand.
AB  - The 2001 outbreak of Foot-and-Mouth Disease (FMD) in the United Kingdom
      heightened public concern in New Zealand about the economic consequences of an
      outbreak of FMD, and resulted in the Reserve Bank and Treasury conducting an
      assessment of the macro-economic impact of a small FMD outbreak in New Zealand.
      The study was based on a relatively small outbreak in which 50 properties were
      infected over a period of two months. Cumulative losses calculated over two years
      from the beginning of the hypothetical outbreak were estimated at around NZ
      dollars 10 billion, a figure twice as large as the initial Ministry of
      Agriculture and Forestry estimate. The main reason for this difference is that
      the Reserve Bank study included the additional macro-economic effects of a slump
      in domestic demand. The study also demonstrated that in New Zealand under the
      conditions of the current OIE Terrestrial Animal Health Code for FMD, the
      economic impact of any programme to control FMD by vaccination in which
      vaccinated animals are not slaughtered, is significantly worse than rapid
      eradication by stamping out.

PMID- 15742661
TI  - Vaccination in the control of bluetongue in endemic regions: the South African
      experience.
AB  - The eradication of bluetongue virus (BTV) from endemic regions of Africa is
      virtually impossible due to the role played by the widely distributed Culicoides
      spp. of midge vectors and the ubiquitous distribution of reservoir species. In
      endemic areas attempts can only be made to limit the occurrence of bluetongue
      (BT) disease and its economic impact through vaccination. Despite several
      potential problems (teratogenicity, risk of reassortment and reversion to
      virulence of the attenuated viral strains), epidemiological and recent molecular
      data support the fact that the live attenuated vaccine that has been used for
      decades in enzootic regions, provides a safe and efficacious means to control the
      disease in regions of southern Africa, as well as other areas of the world.

PMID- 15742662
TI  - Bovine brucellosis control and eradication programme in Chile: vaccine use as a
      tool within the programme.
AB  - In 1975 Chile began the bovine brucellosis control programme in the south central
      area of the country, where the 92% of the bovine population is located. In 1992
      the programme was evaluated and the prevalence showed almost no change for the
      last nine years, Therefore, a comprehensive Brucellosis eradication programme
      began. Based on the information gathered by a surveillance system on cattle
      market and dairy herds from 1999 to 2003 the advances in the process are shown.
      By applying this programme it has been possible to eradicate brucellosis from the
      XII Region, and in 2003 was declared brucellosis free with vaccination. In Region
      XI the project is in its final year and during the last semester no reactor
      animals have been found. The central south regions began their eradication in
      1996. This is the area of the country where the largest bovine population is
      concentrated, and also the highest brucellosis prevalence. Now the situation has
      been changing and the trend shows fewer reactors in auction markets and milk
      plants. The effect of the vaccine (Strain 19 at the beginning and Strain RB 51
      from 1997) has been important in impeding the infection of negative herds that
      are in infected areas. It is also used with success in infected herds, applying
      "whole herd vaccination" to create a quick herd immunity. This has been important
      since in Chile there is no paid compensation for reactor animals and the infected
      animals remain for a variable period in the herd before being destroyed.

PMID- 15742663
TI  - Use of new adjuvants in an emergency vaccine against foot-and-mouth disease
      virus: evaluation of conferred immunity.
AB  - The ability of an emergency adjuvanted FMDV vaccine to elicit early protective
      immune response in mice was examined. We studied the efficacy of several
      adjuvants to induce such protection. The aqueous IMS1313 plus inactivated FMDV
      induce a higher protective immune response than the vaccine with inactivated
      virus alone at seven days post vaccination (dpv). Mice vaccinated with this
      formula showed higher lymphoproliferative index values and higher IL-2, IL-4 and
      IFNgamma levels than the controls.

PMID- 15742664
TI  - Standardized 3D documentation for neurosurgery.
AB  - OBJECTIVE: Although direct volume visualization is now a standard tool for
      diagnosis and therapy planning for medical conditions in the brain, its
      application is normally restricted to radiological workstations. We propose the
      use of standardized digital video sequences which can be easily ported to mobile
      computing platforms and thereby to diverse clinical environments. The
      effectiveness of this approach is demonstrated in the operating room. MATERIALS
      AND METHODS: Segmented MR data corresponding to neurovascular compression
      syndrome pathologies was examined with 3D visualization based on tagged volumes.
      CT-angiography data containing aneurysms close to the skull base was analyzed
      with volume visualization based on bidimensional transfer functions. Furthermore,
      automatic adjustment of bidimensional transfer function templates was
      implemented. An extension of the applied volume visualization tool made it
      possible to standardize the creation of pathology-specific digital video
      sequences. RESULTS: Five cases of neurovascular compression syndromes and 4 cases
      of aneurysms close to the skull base were examined. One-dimensional transfer
      function templates were successfully applied for the visualization of
      neurovascular compression syndromes. Automatic adjustment of transfer function
      templates made it possible to achieve good-quality results for visualization of
      aneurysms without external adjustment. The resulting digital video sequences were
      successfully used in the operating room. CONCLUSION: The portability of the 3D
      video sequences broadens their application spectrum, making them adequate not
      only for database purposes, but also for surgical support and cooperative
      environments. Furthermore, the required technical knowledge is encapsulated,
      making this approach more suitable for clinical applications.

PMID- 15742665
TI  - Fundamentals of force feedback and application to a surgery simulator.
AB  - Force feedback increases the effectiveness of virtual-reality surgery training
      systems. An overview of the fundamentals of applying force feedback is presented.
      An impedance control technique and data processing methods for stability
      preservation are illustrated. A flexible interface for general force-feedback
      applications has been developed. This interface is capable of controlling several
      different force-feedback hardware systems, including the SensAble PHANTOM, the
      Laparoscopic Impulse Engines from Immersion, and the VS-One virtual endoscopic
      surgery trainer. The findings are evaluated using the main simulation system,
      KISMET, and the modeling tools KISMO and VESUV. Within the scope of a cooperative
      project called HapticIO (funded by the German Ministry of Education and Research
      [BMBF]), new haptic devices have been designed for virtual neuroendoscopy and
      laparoscopy. The concept and implementations presented in this paper have been
      found to be flexible, stable and suitable for universal use. The impedance
      method, combined with the open-loop feed-forward control technique, is well
      suited and appropriate for the task.

PMID- 15742666
TI  - A navigated mechatronic system with haptic features to assist in surgical
      interventions.
AB  - OBJECTIVE: In orthopaedic surgery, the development of new computer-based
      technologies such as navigation systems and robotics will facilitate more
      precise, reproducible results in surgical interventions. There are already
      commercial systems available for clinical use, though these still have some
      limitations and drawbacks. This paper presents an alternative approach to a
      universal modular surgical assistant system for supporting less or minimally
      invasive surgery. MATERIALS AND METHODS: The position of a mechatronic arm, which
      is part of the system, is controlled by a navigation system so that small patient
      movements are automatically detected and compensated for in real time. Thus, the
      optimal tool position can be constantly maintained without the need for rigid
      bone or patient fixation. Furthermore, a force control mode of the mechatronic
      assistant system, based on a force-torque sensor, not only increases safety
      during surgical interventions but also facilitates hand-driven direct positioning
      of the arm. RESULTS: A prototype has been successfully tested in clinical
      applications at the Orthopadische Universitatsklinik Frankfurt. For the first
      time worldwide, implantation of the cup prosthesis in total hip replacement
      surgery has been carried out with the assistance of a mechatronic arm. According
      to measurements by the digitizing system, operating tool angle deviation remained
      below 0.5 degrees, relative to the preoperative planning. CONCLUSION: The
      presented approach to a new kind of surgical mechatronic assistance system
      supports the surgeon as needed by optimal positioning of the surgical
      instruments. Due to its modular design, it is applicable to a wide range of tasks
      in surgical interventions, e.g., endoscope guidance, bone preparation, etc.

PMID- 15742667
TI  - Automated registration of partially defective surfaces by local landmark
      identification.
AB  - OBJECTIVE: In computer- and robot-assisted surgery, the term "registration"
      refers to the definition of the geometrical relationship between the coordinate
      system of a surgical planning system and that of the patient. Within the context
      of the development of a navigation and control system for computer- and robot
      assisted surgery of the lateral skull base, it was desirable to realize an
      algorithm for automated registration of partially defective surfaces that is
      reliable and suitable for use in clinical practice. MATERIALS AND METHODS: A
      registration algorithm based on the use of local fingerprints for specific points
      on a surface (so-called "spin images") was developed. Anatomical patient
      landmarks were identified automatically and assigned to CT data, performing a
      cross-correlation analysis and an investigation of the geometrical consistency.
      The algorithm was evaluated within the development of the navigation and robotic
      control system in a laboratory setting. RESULTS: Under laboratory conditions it
      could be shown that partially defective surfaces (simulated by, for example,
      adding white noise, or reducing or smoothing the polygon data) were correctly
      recognized and thereby registered. In particular, the algorithm proved its
      excellence in interpreting partially modified topologies. CONCLUSIONS: The
      proposed procedure can be used to accomplish dynamic intra-operative registration
      of the skull bone by the generation of point relations to the CT images.

PMID- 15742668
TI  - Intra-operative support via augmented reality techniques in endoscopic surgery.
AB  - Computer assisted operation planning systems are gaining increasing recognition
      in the field of surgery. These systems offer new possibilities for preparing an
      intervention, with the goal of reducing the amount of expensive operating-room
      time required for the intervention. The safest and most effective surgical
      approach should always be selected, but it is often difficult to transfer the
      output of the planning system to the intra-operative situation so that the
      planning results can be considered during the actual intervention. At the
      Fraunhofer Institute for Computer Graphics (IGD) in Darmstadt and the Centre for
      Advanced Media Technology (CAMTech) in Singapore methods are being developed to
      bridge the gap between the external planning session and the intra-operative
      case: Augmented Reality (AR) techniques are used to overlay preoperative scanned
      image data, as well as results of the planning session, on the operation field.

PMID- 15742669
TI  - Housing, health and well-being: moving forward.

PMID- 15742670
TI  - Gender differences in the relationship between housing, socioeconomic status, and
      self-reported health status.
AB  - This study investigates gender differences in housing, socioeconomic status, and
      self-reported health status. The analysis focuses on the social and economic
      dimensions of housing, such as demand, control, material aspects (affordability,
      type of dwelling) and meaningful aspects (pride in dwelling, home as a refuge) of
      everyday life in the domestic environment. A random sample, cross-sectional
      telephone survey was administered in the city of Vancouver, Canada in June 1999
      (n = 650). Survey items included measures of material and meaningful dimensions
      of housing, housing satisfaction, and standard measures of socioeconomic status
      and social support. The main outcome measure was self-reported health
      (excellent/very good/good vs. fair/poor). A three-stage analysis provides an
      overall picture of the sample characteristics for male and female respondents,
      detects significant relations between individual and housing characteristics and
      self-rated health status, and investigates male-female differences in the factors
      associated with fair/poor self-rated health. In multivariate analyses, a small
      number of socioeconomic dimensions of housing were associated with self-rated
      health status for women. For men, only one attribute of housing was associated
      with self-rated health: crowding was positively related to poor health,
      contradicting expectations and the findings for women. The self-reported strain
      of housework was unrelated to self-rated health for men, but strongly related to
      poor health for women. For men and women, satisfaction with social activities
      increased the likelihood of reporting better health. Future research should focus
      on the health effects of gendered differences in domestic and paid work, and on
      home and family roles and the interaction among gender, household crowding, and
      health.

PMID- 15742671
TI  - Interventions to improve children's health by improving the housing environment.
AB  - Young children spend more than 90% of their time in the household environment--a
      likely place of exposure to hazardous substances. In the developing world,
      childhood diarrheal disease and acute lower respiratory infections represent a
      large portion of the global burden of disease and are strongly related to housing
      conditions. In the developed world, allergies and asthma are also strongly linked
      to housing conditions. Therefore, intervention to improve housing is essential to
      improve and maintain children's health. This paper will review several factors
      that have been shown to mediate housing and health relations, including
      psychosocial, environmental, socioeconomic, behavior-cultural, and physiological
      factors, and will provide examples of intervention to improve child health, with
      housing as a focus. Environmental contaminants found in the household include
      biological (for example, vector-borne diseases, dustmites, mold, water- and
      sanitation-related), chemical (for example, lead, volatile organic compounds,
      asbestos) or physical (for example, radon, electric and magnetic fields).
      Socioeconomic factors include household income, the ability to obtain adequate
      and appropriate housing, and the ability to implement ongoing preventative
      maintenance. Housing tenure has been used as a proxy for socioeconomic status and
      shown some relation with health outcome. Socioeconomic factors can be relevant to
      the ability of households to create social networks that affect health.
      Psychosocial factors, including stress and depression, can also be related to
      housing type or design. Behavioral-cultural factors include practices that might
      influence exposure to chemical, biological, or radiation hazards like time
      activity patterns, including gender relations and household decision-making
      patterns. Physiological factors include genetics or the nutritional and immune
      status of household members, which can influence the extent to which other
      housing factors like biological or chemical contaminants adversely affect
      children. Examples of intersectoral interventions and strategies to improve child
      health globally, with housing and health as a focus, include integrated pest
      management programs to control vector-borne diseases like malaria and Chagas
      disease and energy-efficiency programs to improve thermal comfort and to reduce
      the presence of allergens like mold and dustmites. Other interventions include
      housing and health policy, regulation and standard setting, education, training,
      and participation.

PMID- 15742672
TI  - Housing and health in later life.
AB  - The goal of this paper is to compile recent data on the housing and health in old
      age, with special emphasis on geropsychological and gerontological studies. The
      authors first introduce their understanding of both housing and health. Second,
      theoretical models that are important to understand better the relation between
      housing- and health-related outcomes are incorporated into an analytic scheme.
      Third, data on objective and subjective aspects of housing in old age in relation
      to health-related outcomes are presented. Among the objective functional housing
      aspects are health-relevant micro-environmental indicators like housing hazards
      and amenities, retrofitting and assistive devices, as well as meso- and macro
      environmental indicators like housing type, neighborhood conditions, or urban
      rural differences. Relocation is a classic field in environmental gerontology in
      which drastic environmental change has been linked to health outcomes. Among
      subjective housing aspects are residential satisfaction, housing-related control
      beliefs, and meaning of home. Direct health-related outcomes, such as physical
      and mental diseases and functional limitations, as well as indirect health
      related outcomes like satisfaction or well-being receive attention. We conclude
      with a discussion addressing the environment and health dynamics of aging in the
      future.

PMID- 15742673
TI  - Home safety in the U.K.: review of the influence of human and housing factors.
AB  - Injuries and deaths from home accidents are a major public health problem. This
      paper describes how data on housing characteristics were matched with dwelling
      related mortality and injuries data. As no single database provided sufficient
      accurate data on housing and occupiers, this task involved identifying datasets
      to create and validate a Housing and Population Database, which was matched with
      various datasets on injuries and fatalities that are associated with the home.
      Taking account of both frequency of accidents and severity of outcomes, analyses
      of the matched data showed the true rank order of type of home accidents. Also
      investigated was whether one age group was more vulnerable to a particular type
      of accident and the relation between different types of accidents and the age and
      type of dwelling. A literature review was carried out to look at the relation
      between the design and condition of dwelling features and accidents and between
      human behavior and accidents. The results showed that little work has been done
      in most areas on the different degrees of the contribution made by human behavior
      and building conditions. Even though more focused research would be useful,
      preventative actions could reduce the scale of the problem.

PMID- 15742674
TI  - Investigations into the indoor environment and respiratory health in Boston
      public housing.
AB  - The self-reported prevalence of asthma in the United States increased by 75% from
      1980 to 1994, a trend found to be significant and evident in every region of the
      country. The increase was most marked in children from birth to 14 years of age;
      and growing evidence indicates that, as with lead poisoning, inner-city and urban
      populations are most at risk. Attention has turned to the role of indoor
      environmental risk factors, especially in homes and schools. Such factors include
      moisture and mold growth, pest infestation, dust mites, the building envelope,
      heating systems, inadequate ventilation, nitrogen dioxide, and environmental
      tobacco smoke. The Healthy Public Housing Initiative (HPHI) is a Boston-based
      community-centered research and intervention project designed to engage Boston
      Housing Authority residents in a collaborative process to improve respiratory
      health, quality of life, building conditions, and building maintenance in public
      housing. This article summarizes the significant research findings from four
      pilot studies in housing developments that laid the foundation for the larger
      HPHI asthma-related environmental intervention study. The research design for the
      pilot projects is informed by principles of community-collaborative research. The
      strengths of this model of research for our work are also discussed.

PMID- 15742676
TI  - Housing and health transition in Thailand.
AB  - Over the past half-century, Thailand's health profile has been undergoing an
      epidemiologic transition in association with various fundamental societal
      changes, shifting from one with a predominant burden of communicable disease to
      one in which noncommunicable diseases and accidents now predominate. The primary
      question is why have the disease rates in the Thai population changed? Answering
      this question requires an examination of the underlying transitions in social and
      contextual factors. This paper explores, using published data, how housing
      conditions, as one set of environmental health risks, have undergone transition
      in recent years and how this change maps on the health-transition process. A
      combination of economic development, urbanization, modernization, and increased
      health literacy resulted in a range of health-protecting changes in housing
      design and materials. Pre-eminent among such changes are improvements in
      household sanitation and in equipment, ventilation, and fuel pertaining to indoor
      cooking and heating. In tropical countries like Thailand, gains have been made in
      mosquito-proofing houses and in minimizing open pools of water to combat the
      risks of malaria, dengue fever, and other mosquito-borne infections. Meanwhile,
      the growth in shantytown and slum housing around the urban fringe, often in
      precarious environmental settings, introduced a negative dimension to the
      evolving profile of housing-related health risks, whereas the urban sprawl of
      modern residences creates health risks that are due to traffic crashes and the
      lack of walking in daily transport.

PMID- 15742677
TI  - Housing, urban development and health in Latin America: contrasts, inequalities
      and challenges.
AB  - Since the outset of the 20th century, growing urbanization and its contingent
      waxing populations in Latin America, including Brazil, have come to have alarming
      effects on the conditions of life, especially in the areas of housing and
      healthcare for such populations. In this paper, we present data describing and
      qualifying the process of urbanization and its consequences for Latin American
      countries and certain Brazilian cities. Arguments are presented about the effects
      of the urbanization process and the development of low-income human settlements
      (slums known as favelas and squatting in tenement housing) on health conditions,
      diseases, and the death rate. The first part of the paper is based on secondary
      and quantitative data about urbanization, housing, and health in Brazilian and
      other Latin American cities. Governmental and nongovernmental data are used to
      structure the problematic landscape of the Latin American region. In the second
      part of the paper, we focus on a case study of a Brazilian coast city that has
      registered an intense population growth. This study demonstrates that urban
      policy (housing, environmental, sanitation, and urban transportation) requires an
      integration of health and environmental public policy and demonstrates the
      importance of the role of popular participation in urban public policy-making,
      and the potential importance of the Bertiioga Healthy City Project from the
      perspective of a better integration of actions, policies, and programs.

PMID- 15742675
TI  - Health impact of environmental tobacco smoke in the home.
AB  - Environmental tobacco smoke (ETS) can be a major constituent of air pollution in
      indoor environments, including the home. Regulation on smoking in the workplace
      and public places has made the home the dominant unregulated source of ETS, with
      important potential impacts on children. Between 40% and 60% of children in the
      United Kingdom are exposed to ETS in the home. Many experimental and human and
      studies have investigated the adverse health effects of ETS. Substantial evidence
      shows that in adults ETS is associated with increased risk of chronic respiratory
      illness, including lung cancer, nasal cancer, and cardiovascular disease. In
      children, ETS increases the risk of sudden infant death syndrome, middle ear
      disease, lower respiratory tract illness, prevalence of wheeze and cough, and
      exacerbates asthma. Although banning smoking in the home would be the optimal
      reduction strategy, several barrier and ventilation methods can be effective.
      Nevertheless, such methods are not always practical or acceptable, particularly
      when social pressures contribute to a lack of support for ETS control in the
      home. Smoking cessation interventions have had limited success. Research is
      needed to explore the barriers to adopting ETS risk-reducing behaviors.

PMID- 15742678
TI  - Lead poisoning in South African children: the hazard is at home.
AB  - Lead is a toxic heavy metal that has been used extensively in modern society,
      causing widespread environmental contamination even in isolated parts of the
      world. Irrefutable evidence associates lead at different exposure levels with a
      wide spectrum of health and social effects, including mild intellectual
      impairment, hyperactivity, shortened concentration span, poor school performance,
      violent/aggressive behavior, and hearing loss. Lead has an impact on virtually
      all organ systems, including the heart, brain, liver, kidneys, and circulatory
      system, resulting in coma and death in severe cases. In recent years, a consensus
      was reached regarding the absence of a threshold for the key health effects
      associated with lead exposure and the permanent and irreversible nature of many
      health and social consequences of lead exposure. The public health problem of
      environmental lead exposure has been widely investigated in developed countries
      like the United States of America, where actions taken have led to significant
      reductions in children's blood lead concentrations. In contrast, there is a
      relative dearth of information and action regarding lead poisoning in developing
      countries, particularly in African countries, despite evidence of widespread and
      excessive childhood lead exposure. In this paper, we will review the information
      from available published papers, the 'grey literature', and unpublished reports
      to give an overview of lead exposure in South African children over the past two
      decades, with particular emphasis on sources of exposure in the home environment.

PMID- 15742679
TI  - Homelessness--on the health agenda in Wales?
AB  - Building a sustainable and inclusive future for Wales is at the heart of the
      constitution of the National Assembly for Wales, which means forging a
      crosscutting approach to social policy. Improving health is a strategic priority
      within this agenda, and homelessness and housing appear to be at the center of
      the Assembly Government's vision of developing sustainable and cohesive
      communities and promoting social inclusion. This article considers the links
      between homelessness and mental and physical ill health and the importance of
      combating homelessness and poor housing within the health agenda in Wales. The
      article cites the links between homelessness and health identified in the United
      Kingdom and in international research and highlights the growth in homelessness
      witnessed during the late 1990s and beginning of the 21st Century. The paper
      considers the significant increase of homelessness and assesses whether, in
      reality, sufficient practical measures are being taken to combat homelessness as
      a means of tackling ill health in Wales. The authors conclude that although Wales
      is making progress toward an integrated approach to health and well-being and
      that the need to tackle broader health determinants has gained recognition,
      investment in effectively tackling homelessness and exclusion is needed.
      Integrating the broader housing, homelessness, and health agendas could
      contribute to health gains in Wales.

PMID- 15742680
TI  - Residential environment and health: a review of methodological and conceptual
      issues.
AB  - Geographic patterns of poor health and mortality risk are found in most
      countries. Important health effects at the neighborhood level are mortality,
      general health, illness and disabilities, mental health, and healthcare
      utilization. Awareness of the influence of social class on health has been
      growing during the last decades. Studies show that individuals with lower
      socioeconomic status (SES) have a shorter life expectancy than do their 'well
      off' counterparts. Yet SES-related health inequalities cannot be fully explained
      by individual characteristics, and environmental qualities should be taken into
      account. Many aspects of local areas that might be related to health or access to
      opportunities to live healthily are systematically poorer in socially
      disadvantaged areas. Such factors have the potential to explain health
      differences between deprived and prosperous neighborhoods. Investigating health
      differences at the neighborhood level implies conceptual as well as
      methodological issues pertaining to selection, accumulation, multiple level
      measurement, objective features versus perceptions, and time dynamic aspects.
      This article reviews such issues and evaluates several exemplary theoretical
      approaches from the fields of public health and environmental health in their
      ability to overcome such problems.

PMID- 15742681
TI  - AVMA, Heifer International team up to bring tsunami aid.

PMID- 15742682
TI  - Tug-of-war.

PMID- 15742683
TI  - The Canada debate. USDA sends team to Canada to investigate BSE situation.

PMID- 15742684
TI  - Exam question is music to students' ears.

PMID- 15742687
TI  - Questions annual loss of manatees.

PMID- 15742685
TI  - In defense of vegetarian cat food.

PMID- 15742688
TI  - Mentors needed.

PMID- 15742690
TI  - What is your diagnosis? Sand enteropathy.

PMID- 15742689
TI  - The majority view of ethics and professionalism in alternative medicine.

PMID- 15742686
TI  - Yet another perspective on TNR.

PMID- 15742691
TI  - What is your diagnosis? Abscessed lymph node.

PMID- 15742692
TI  - ECG of the month. Sinus rhythm with supraventricular premature complexes.

PMID- 15742693
TI  - Compendium of measures to control Chlamydophila psittaci (formerly Chlamydia
      psittaci) infection among humans (psittacosis) and pet birds, 2005.
AB  - Psittacosis, also known as parrot fever and ornithosis, is a bacterial infection
      of humans that can cause severe pneumonia and other serious health problems. It
      is caused by Chlamydophila psittaci, formerly known as Chlamydia psittaci. From
      1988 through 2003, 935 human cases of psittacosis were reported to the CDC and
      most resulted from exposure to infected pet birds, usually cockatiels, parakeets,
      parrots, and macaws. In birds, C. psittaci infection is referred to as avian
      chlamydiosis. Infected birds shed the bacteria through feces and nasal
      discharges, and humans become infected from exposure to these materials. This
      compendium provides information about psittacosis and avian chlamydiosis to
      public health officials, physicians, veterinarians, the pet bird industry, and
      others concerned with controlling these diseases and protecting public health.
      The recommendations in this compendium provide standardized procedures for
      controlling avian chlamydiosis in birds, a vital step to protecting human health.
      This document will be reviewed and revised as necessary.

PMID- 15742694
TI  - Epidemiologic features of Campylobacter infection among cats in the upper
      midwestern United States.
AB  - OBJECTIVE: To describe the epidemiologic features of Campylobacter infection
      among cats in the Minneapolis-Saint Paul metropolitan area. DESIGN: Prevalence
      survey. ANIMALS: 152 cats examined at 3 private veterinary clinics and an animal
      humane society. PROCEDURES: Fecal samples were submitted for bacterial culture
      for Campylobacter spp. To determine the duration of Campylobacter carriage,
      follow-up fecal samples were collected from cats with positive Campylobacter
      culture results. RESULTS: Campylobacter organisms were cultured from 37 of the
      152 (24%) fecal samples. Campylobacter isolates were identified as Campylobacter
      upsaliensis (29 cats), Campylobacter jejuni (2), and Campylobacter coli (1);
      species of the remaining 5 isolates could not be determined. Campylobacter
      organisms were isolated from 36 of the 122 (30%) cats that were < or = 1 year old
      but from only 1 of the 30 (3%) cats that were > 1 year old, and shedding was more
      common during the summer and fall months. No association between Campylobacter
      shedding and clinical signs of disease was identified. For 4 of 13 cats from
      which follow-up fecal samples were obtained, duration of Campylobacter carriage
      could not be determined because Campylobacter organisms were isolated from all
      follow-up samples. For the remaining 9 cats, median duration of Campylobacter
      carriage was 44 days. CONCLUSIONS AND CLINICAL RELEVANCE: C. upsaliensis can
      commonly be isolated from the feces of overtly healthy kittens in the Midwest
      United States. Because carriage may be prolonged, veterinarians should encourage
      good hand hygiene among owners of cats, especially among owners with new kittens
      in their household.

PMID- 15742695
TI  - Assessment of stress levels among cats in four animal shelters.
AB  - OBJECTIVE: To measure stress levels among cats in traditional and enriched
      shelter environments via behavioral assessment and urine cortisol-to-creatinine
      ratios. DESIGN: Cross-sectional observational study. ANIMALS: 120 cats in 4
      Boston-area animal shelters. PROCEDURE: Cats were randomly selected and observed
      during 3 periods (morning, midday, and afternoon) of 1 day and scored by use of a
      behavioral assessment scale. The next day, urine samples were collected for
      analysis of the urine cortisol-to-creatinine ratio. Information about each cat's
      background before entering the shelter was collected. RESULTS: Stress scores were
      highest in the morning. The relationships between the amount of time cats spent
      in the shelter and the cat stress score or urine cortisol-to-creatinine ratio
      were not strong. There was no correlation between the cat stress score and urine
      cortisol-to-creatinine ratio. Urine cortisol-to-creatinine ratios did correlate
      with signs of systemic disease and were significantly lower in cats in the more
      environmentally enriched shelters, compared with cats in the traditional
      shelters. Urine cortisol-to-creatinine ratio was highest among cats with high
      exposure to dogs. Of the cats in the study, 25% had subclinical hematuria
      detectable on a urine dipstick. CONCLUSIONS AND CLINICAL RELEVANCE: In this
      study, the cat stress score was not a useful instrument for measuring stress
      because it failed to identify cats with feigned sleep and high stress levels.
      Urine cortisol-to-creatinine ratios can be monitored to noninvasively assess
      stress levels in confined cats. Environmental enrichment strategies may help
      improve the welfare of cats in animal shelters.

PMID- 15742696
TI  - Secretion of sex hormones in dogs with adrenal dysfunction.
AB  - OBJECTIVE: To evaluate adrenal sex hormone concentrations in response to ACTH
      stimulation in healthy dogs, dogs with adrenal tumors, and dogs with pituitary
      dependent hyperadrenocorticism (PDH). DESIGN: Prospective study. ANIMALS: 11
      healthy control dogs, 9 dogs with adrenal-dependent hyperadrenocorticism
      (adenocarcinoma [ACA] or other tumor); 11 dogs with PDH, and 6 dogs with
      noncortisol-secreting adrenal tumors (ATs). PROCEDURE: Hyperadrenocorticism was
      diagnosed on the basis of clinical signs; physical examination findings; and
      results of ACTH stimulation test, low-dose dexamethasone suppression test, or
      both. Dogs with noncortisol-secreting ATs did not have hyperadrenocorticism but
      had ultrasonographic evidence of an AT. Concentrations of cortisol,
      androstenedione, estradiol, progesterone, testosterone, and 17
      hydroxyprogesterone were measured before and 1 hour after i.m. administration of
      0.25 mg of synthetic ACTH. RESULTS: All dogs with ACA, 10 dogs with PDH, and 4
      dogs with ATs had 1 or more sex hormone concentrations greater than the reference
      range after ACTH stimulation. The absolute difference for progesterone, 17
      hydroxyprogesterone, and testosterone concentrations (value obtained after ACTH
      administration minus value obtained before ACTH administration) was significantly
      greater for dogs with ACA, compared with the other 3 groups. The absolute
      difference for androstenedione was significantly greater for dogs with ACA,
      compared with dogs with AT and healthy control dogs. CONCLUSIONS AND CLINICAL
      RELEVANCE: Dogs with ACA secrete increased concentrations of adrenal sex
      hormones, compared with dogs with PDH, noncortisol-secreting ATs, and healthy
      dogs. Dogs with noncortisol-secreting ATs also have increased concentrations of
      sex hormones. There is great interdog variability in sex hormone concentrations
      in dogs with ACA after stimulation with ACTH.

PMID- 15742697
TI  - Comparison of results of clinicians' assessments, cytologic examination of fine
      needle lymph node aspirates, and flow cytometry for determination of remission
      status of lymphoma in dogs.
AB  - OBJECTIVE: To determine interclinician agreement when assessing remission of
      lymphoma in dogs and the association among results of clinicians' assessments via
      lymph node palpation, cytologic examination of fine-needle lymph node aspirates,
      and flow cytometry as determinants of remission. DESIGN: Prospective study.
      ANIMALS: 23 dogs with untreated lymphoma. PROCEDURE; Two clinicians independently
      measured large lymph nodes and cytologic examination and flow cytometry of cells
      from a mandibular or popliteal lymph node were performed 1 week prior to
      initiating treatment. Lymph node measurements with clinicians' remission
      assessments and cytologic examination were repeated at weeks 2, 3, and 5; flow
      cytometry was repeated at week 5. RESULTS: Significant correlation was identified
      between clinicians' remission assessments. Significant correlation between lymph
      node palpation and cytologic examination was identified at week 5, but not at
      weeks 2 and 3. Lymphoma was diagnosed in 16 of 23 (70%) dogs at initial
      evaluation by use of flow cytometry, although it was of limited use at subsequent
      evaluations and results were not diagnostic of lymphoma in any dog at week 5,
      including 1 dog in which lymphoma was diagnosed cytologically. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that physical examination and measurement
      of lymph node volume may not be sufficient for accurately determining remission,
      that flow cytometry alone should not be relied on as a means for diagnosis, and
      that cytologic examination of fine-needle lymph node aspirates should be
      considered as the most accurate means of determining remission status at times in
      which treatment modifications are considered.

PMID- 15742698
TI  - Evaluation of client compliance with short-term administration of antimicrobials
      to dogs.
AB  - OBJECTIVE: To describe the degree of and variability in the level of client
      compliance and identify determinants of client compliance with short-term
      administration of antimicrobial medications to dogs. DESIGN: Prospective study.
      SAMPLE POPULATION: 90 owners of dogs prescribed antimicrobials. PROCEDURE:
      Eligible clients were invited to participate when antimicrobial medications were
      dispensed. Data were collected during a follow-up appointment by use of a client
      questionnaire, residual pill count, and return of an electronic medication
      monitoring device. Attending veterinarians also completed a questionnaire that
      asked them to predict client compliance. Methods of assessing compliance were
      compared with nonparametric tests. Generalized estimating equations were used to
      investigate potential determinants of compliance. RESULTS: Median compliance
      rates of 97% of prescribed container openings, 91% of days when the correct
      number of doses were given, and 64% of doses given on time as assessed by the
      electronic medication monitoring devices were significantly lower than the median
      compliance rates of 100% for client self-report of missing doses and pill count.
      Veterinarians were unable to predict client compliance. The dosage regimen
      significantly determined compliance. Clients giving antimicrobials once or twice
      daily were 9 times more likely to be 100% compliant, compared with 3 times daily
      dosing. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of reported missed
      doses and pill counts was a significant predictor of compliance as measured by
      electronic monitoring. Electronic monitoring caps provided useful information
      only when they were used appropriately. Asking clients about missed doses and
      performing pill counts are the most practical assessments of compliance in
      practice.

PMID- 15742699
TI  - Survival times in dogs with right atrial hemangiosarcoma treated by means of
      surgical resection with or without adjuvant chemotherapy: 23 cases (1986-2000).
AB  - OBJECTIVE: To determine survival times in dogs with right atrial hemangiosarcoma
      treated by means of pericardectomy and tumor resection, with or without adjuvant
      chemotherapy, and identify complications associated with treatment. DESIGN:
      Retrospective study. ANIMALS: 23 dogs. PROCEDURE: Dogs were included only if the
      diagnosis was confirmed histologically. RESULTS: The most common initial
      complaints included acute collapse (8 [35%] dogs), anorexia or inappetence (8
      [35%]), and lethargy (8 [35%]). The most common physical examination
      abnormalities included muffled heart sounds (12 [52%] dogs), tachycardia (7
      [30%]), and weak pulses (7 [30%]). Postoperative complications developed in 12
      (52%) dogs; however, most complications were minor. Twenty (87%) dogs were
      discharged from the hospital. Survival time was significantly longer in the 8
      dogs that received adjuvant chemotherapy (mean, 164 days; median, 175 days) than
      in the 15 dogs that did not receive chemotherapy (mean, 46 days; median, 42
      days). Dogs that received chemotherapy were significantly younger and had
      significantly lower WBC counts than did dogs that did not receive chemotherapy.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with right
      atrial hemangiosarcoma, surgical resection of the tumor was associated with a low
      complication rate and complications that did arise typically were minor. In
      addition, use of adjuvant chemotherapy following resection was associated with
      significantly longer survival times, compared with resection alone.

PMID- 15742700
TI  - Community-associated methicillin-resistant Staphylococcus aureus in horses and
      humans who work with horses.
AB  - OBJECTIVE: To evaluate the prevalence of nasal colonization with methicillin
      resistant Staphylococcus aureus (MRSA) in horses and horse personnel. DESIGN:
      Prospective prevalence study. SAMPLE POPULATION: 972 horses and 107 personnel
      from equine farms in Ontario, Canada and New York state. PROCEDURE: Nasal swab
      specimens were collected from horses and humans on farms with (targeted
      surveillance) and without (nontargeted surveillance) a history of MRSA
      colonization or infection in horses during the preceding year. Selective culture
      for MRSA was performed. Isolates were typed via pulsed-field gel electrophoresis,
      and antibiograms were determined. RESULTS: MRSA was isolated from 46 of 972
      (4.7%) horses (0/581 via nontargeted surveillance and 46/391 [12%] via targeted
      surveillance). Similarly, MRSA was isolated from 14 of 107 (13%) humans (2/41
      [5%] from nontargeted surveillance and 12/66 [18%] from targeted surveillance).
      All isolates were subtypes of Canadian epidemic MRSA-5, an uncommon strain in
      humans. All isolates were resistant to at least 1 antimicrobial class in addition
      to beta-lactams. On all farms with colonized horses, at least 1 human was
      colonized with an indistinguishable subtype. For horses, residing on a farm that
      housed > 20 horses was the only factor significantly associated with MRSA
      colonization. For humans, regular contact with > 20 horses was the only
      identified risk factor. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm a
      reservoir of colonized horses on a variety of farms in Ontario and New York and
      provide evidence that 1 MRSA strain is predominantly involved in MRSA
      colonization in horses and humans that work with horses.

PMID- 15742702
TI  - Antimicrobial susceptibility of Escherichia coli isolates from dairy farms using
      organic versus conventional production methods.
AB  - OBJECTIVE: To compare antimicrobial susceptibility patterns of Escherichia coli
      isolates cultured from fecal samples from cows and calves on dairy farms that
      used organic (ie, no or severely limited antimicrobial use) versus conventional
      production methods. DESIGN: Cross-sectional study. SAMPLE POPULATION: Fecal
      samples from 10 cows and 10 calves on each of 30 organic dairy farms and 30
      neighboring conventional dairy farms in Wisconsin. PROCEDURE: E. coli isolates
      obtained from the fecal samples were tested for susceptibility to 17
      antimicrobials by means of a microbroth dilution test. Prevalence of
      antimicrobial resistance was compared between organic and conventional dairy
      farms. RESULTS: E. coli was isolated from 1,121 (94%) fecal samples. Farm type
      (organic vs conventional) and animal age (cow vs calf) were significantly
      associated with odds that E. coli isolates would be resistant to various
      antimicrobials. After controlling for age, logistic regression analyses indicated
      that isolates from conventional dairy farms had significantly higher rates of
      resistance to ampicillin, streptomycin, kanamycin, gentamicin, chloramphenicol,
      tetracycline, and sulfamethoxazole than did isolates from organic dairy farms.
      However, no significant differences were detected for the 10 other antimicrobials
      that were tested. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that
      compared with isolates from conventional dairy farms, E. coli isolates from
      organic dairy herds have significantly lower prevalences of resistance to 7
      antimicrobials; however, prevalence of resistance was not significantly different
      for 10 other antimicrobials. Resistance was more common for isolates from calves
      than for isolates from adult dairy cows.

PMID- 15742703
TI  - Prevalence, outcome, and health consequences associated with persistent infection
      with bovine viral diarrhea virus in feedlot cattle.
AB  - OBJECTIVE: To estimate prevalence of cattle persistently infected (PI) with
      bovine viral diarrhea virus (BVDV) at arrival at a feedlot, prevalence of
      chronically ill and dead PI cattle, and the magnitude of excess disease
      attributable to a PI animal. DESIGN: Cross-sectional and cohort studies. ANIMALS:
      2,000 cattle at the time they arrived at a feedlot, 1,383 chronically ill cattle
      from 7 feedlots, and 1,585 dead cattle from a single feedlot. PROCEDURE: Skin
      biopsy specimens were collected and evaluated via immunohistochemistry. Cattle
      were characterized as either PI or not PI with BVDV on the basis of
      characteristic immunostaining. Follow-up was obtained for the 2,000 cattle from
      which samples were collected at arrival, and health outcomes were determined for
      cattle exposed and not exposed to a PI animal. RESULTS: Prevalence of PI cattle
      was 0.3% at arrival, 2.6% in chronically ill cattle, and 2.5% in dead cattle.
      Risk of initial treatment for respiratory tract disease was 43% greater in cattle
      exposed to a PI animal, compared with those not exposed to a PI animal. Overall,
      15.9% of initial respiratory tract disease events were attributable to exposure
      to a PI animal. CONCLUSIONS AND CLINICAL RELEVANCE: Relatively few PI cattle
      arrive at feedlots. However, those cattle are more likely to require treatment
      for respiratory tract disease and either become chronically ill or die than
      cattle that are not PI. In addition, they are associated with an increase in the
      incidence of respiratory tract disease of in-contact cattle.

PMID- 15742701
TI  - Diabetes mellitus in a domesticated Spanish mustang.
AB  - An 18-year-old Spanish Mustang mare was referred for evaluation of progressive
      weight loss and persistent hyperglycemia. Clinicopathologic abnormalities
      included marked hyperglycemia and glycosuria. Serum cortisol concentration was
      appropriately decreased following administration of dexamethasone, indicating
      that the horse did not have pituitary pars intermedia dysfunction. Serum insulin
      and plasma C-peptide concentrations were low, suggesting that hyperglycemia was a
      result of decreased secretion of insulin by pancreatic beta cells. In addition,
      glucose concentration did not return to the baseline concentration until 5 hours
      after i.v. administration of a glucose bolus, suggesting that insulin secretion,
      insulin effect, or both were reduced. However, i.v. administration of insulin
      caused only a slight decrease in the plasma glucose concentration, giving the
      impression that the action of insulin was impaired. Within 5 hours after
      administration of a combination of glyburide and metformin, which is used to
      treat diabetes mellitus in humans, the glucose concentration was within reference
      limits. The horse was euthanized, and a postmortem examination was done.
      Immunohistochemical staining of sections of the pancreas revealed attenuation of
      the pancreatic islet beta-cell population, with beta cells that remained
      generally limited to the periphery of the islets. These findings indicate that,
      albeit rare, pancreatic beta-cell failure may contribute to the development of
      diabetes mellitus in horses.

PMID- 15742705
TI  - 2004 Donald E. Cummings Memorial Award Lecture. Industrial hygiene in decline-
      what can we do?
AB  - The Donald E. Cummings Memorial Award was established in 1943 as a tribute to
      Donald E. Cummings, AIHA's third president. It is given for outstanding
      contributions to the knowledge and practice of the profession of industrial
      hygiene. This year's Cummings Award recipient is D. Jeff Burton for his many
      publications and training courses, as well as his involvement in many IH/OH
      organizations.

PMID- 15742706
TI  - Development and characterization of a wake-controlled exterior hood.
AB  - A wake-controlled exterior hood was developed to overcome the negative influence
      of cross draft on an exterior hood and avoid the operation inconvenience caused
      by the enclosure of an airflow capture booth. This new type of local exterior
      hood used the hood suction flow to stabilize the dynamic vortex shedding that was
      induced when a crossflow passed over a blockage plate, and therefore formed a
      hydrodynamics-stabilized local isolation area for efficient removing of the
      contaminant. The development process was performed in a test section of an open
      circuit wind tunnel. The blockage plate and the exterior hood model were placed
      in a wind-tunnel test section so that the crossflow could be freely supplied by
      the airstream of the wind tunnel. The laser light sheet flow visualization method
      and the laser Doppler velocimeter were employed to reveal the characteristics of
      the flow field. Primary influential parameters were factored out of the measured
      velocity results so that a design procedure was proposed. Experiments using hot
      wire type alcohol sensors to measure the toluene vapor concentration
      distributions showed that the capture efficiency of this type of actively
      controlled hood was remarkably higher than that of an uncontrolled hood.

PMID- 15742704
TI  - Ergonomics. A checklist for the ergonomic evaluation of nonpowered hand tools.
AB  - A checklist was developed to evaluate nonpowered hand tools for basic features
      related to good ergonomic tool design. The checklist contains 16 items to which a
      yes/no response is required. The checklist is intended to be used by
      tradespersons and is written in clear, simple language. This column reports on a
      study conducted to examine the reliability of the checklist questions in
      identifying the presence or absence of the basic ergonomic design features that
      are believed to be important for nonpowered hand tools. Using the checklist, 14
      ergonomists and 126 carpenters evaluated 18 typical hand tools. Agreement among
      the carpenters and ergonomists was high for most of the checklist items. A few
      checklist questions were associated with relatively low agreement among raters in
      terms of the presence or absence of a design feature. Lack of agreement between
      raters indicates that the criterion was not explicit or that users had difficulty
      identifying whether the tool satisfied the particular criterion. The majority of
      the 18 hand tools evaluated were deemed to be lacking in multiple highly
      important ergonomic design features. Additional studies are being conducted to
      make appropriate revisions to the checklist criteria based on quantitative
      measures of musculoskeletal loading.

PMID- 15742709
TI  - Application of colorimetric indicators and thermo-hand method to determine base
      permeation through chemical protective gloves.
AB  - The aim of this study was to assess the use of colorimetric indicator pads and
      the thermo-hand method for detection of inorganic/organic base permeation of
      chemical protective gloves under simulated in-use conditions. Breakthrough times
      for four types of gloves were determined based on the color change of pads and
      ranged from 3 to 10 min for butylamine, from 4 min to >4 hours for
      diisopropylamine, from 6 min to >4 hours for triethylamine, and >4 hours for
      sodium hydroxide. Quantification was performed for butylamine, diisopropylamine,
      and triethylamine by gas chromatography following solvent desorption. These
      chemicals exhibited >99% adsorption on the pads at spiking levels of 1.08-1.11:g
      for each base. The recovery for the system was calculated for each chemical, with
      results ranging from 50-74% (RSD < or = 5%) for these bases over the spiking
      range 0.22-1.11 microg. The quantitative mass of the bases on the pads at the
      time of breakthrough detection ranged from 118-121, 117-120, and 109-116
      microg/cm2 for butylamine, diisopropylamine, and triethylamine, respectively. The
      thermo-hand test method and base indicators together should find utility in
      detecting, collecting, and quantitatively analyzing base permeation samples under
      simulated in-use conditions.

PMID- 15742708
TI  - Airborne concentrations of methylene diphenyl diisocyanate (MDI) in North
      American wood mills during the manufacturing of oriented strand board (OSB).
AB  - Air monitoring data were collected from industrial hygiene surveys over an 8-year
      period in oriented strand board (OSB) mills. Personal samples were taken to
      evaluate potential employee exposures to MDI. Area samples were taken to
      determine the effectiveness of control measures used in the mills to prevent
      fugitive emissions of wood dust, MDI, and MDI-coated wood dust from the OSB
      manufacturing process. Personal sampling results (578 samples covering 11
      different job categories) ranged from 0.0002-0.524 mg/m3, with a GM = 0.001 and
      GSD = 3.71. Area sampling results (1657 samples covering 14 stationary locations
      in the mills) ranged from 0.0002-2.5 mg/m3, with a GM = 0.004 and GSD = 5.52. The
      statistical range of the data suggests high variability. While exposures to MDI
      above the established limits (0.051 mg/m3, 8-hour time-weighted average, 0.2
      mg/m3, ceiling) can and do occur when engineering controls are not maintained
      and/or proper work practices and personal protective equipment are not
      followed/used for certain high exposure potential tasks, the data indicate that
      over 97% of the personal and 92% of the area sampling results are less than 0.051
      mg/m3. Wipe testing was performed to determine the presence of removable,
      unreacted diisocyanates (NCO functional groups)from various surfaces. Positive
      results were found in about 13% of the wipe tests on surfaces confined to the
      blender, forming line, and hopper deck process areas.

PMID- 15742707
TI  - Laboratory and field evaluation of a SAW microsensor array for measuring
      perchloroethylene in breath.
AB  - This article describes the laboratory and field performance evaluation of a small
      prototype instrument employing an array of six polymer-coated surface acoustic
      wave (SAW) sensors and a thermal desorption preconcentration unit for rapid
      analysis of perchloroethylene in breath. Laboratory calibrations were performed
      using breath samples spiked with perchloroethylene to prepare calibration
      standards spanning a concentration range of 0.1-10 ppm. A sample volume of 250 mL
      was preconcentrated on 40 mg of Tenax GR at a flow rate of 100 mL/min, followed
      by a dry air purge and thermal desorption at a temperature of 200 degrees C. The
      resulting pulse of vapor was passed over the sensor array at a flow rate of 20
      mL/min and sensor responses were recorded and displayed using a laptop computer.
      The total time per analysis was 4.5 min. SAW sensor responses were linear, and
      the instrument's limit of detection was estimated to be 50 ppb based on the
      criterion that four of the six sensors show a detectable response. Field
      performance was evaluated at a commercial dry-cleaning operation by comparing
      prototype instrument results for breath samples with those of a portable gas
      chromatograph (NIOSH 3704). Four breath samples were collected from a single
      subject over the course of the workday and analyzed using the portable gas
      chromatograph (GC) and SAW instruments. An additional seven spiked breath samples
      were prepared and analyzed so that a broader range of perchloroethylene
      concentrations could be examined. Linear regression analysis showed excellent
      agreement between prototype instrument and portable GC breath sample results with
      a correlation coefficient of 0.99 and a slope of 1.04. The average error for the
      prototype instrument over a perchloroethylene breath concentration range of 0.9
      7.2 ppm was 2.6% relative to the portable GC. These results demonstrate the field
      capabilities of SAW microsensor arrays for rapid analysis of organic vapors in
      breath.

PMID- 15742711
TI  - Time variant exposure analysis (TVEA): a measurement tool for characterizing
      particulate exposure determinants in construction.
AB  - A work sampling-based approach, time variant exposure analysis (TVEA), was
      developed for assessment of determinants for particulate air contaminants in
      dynamic construction environments. To use TVEA, the field researcher records
      observations at fixed intervals to systematically survey over 30 potential
      determinants that could affect exposure to three types of particulate matter:
      quartz-containing dusts, diesel exhaust, and a general grouping of "other
      particles" that includes welding fume and wood dust. Two field studies were
      conducted to address questions of inter-rater reliability (n = 20) and coding
      interval appropriateness (n = 21) for the TVEA method. At least substantial inter
      rater agreement (kappa > 0.60) was obtained for the TVEA variables related to
      tool or machine use, process, material, source intensity, and source orientation.
      Kappa values for source direction (0.22-0.38) and number of sources (0.38-0.60)
      showed comparatively lower agreement for all particulate types. Observation
      interval appropriateness was analyzed using linear regression to compare a 5-min
      observation interval "gold standard" with alternate intervals. Regression
      statistics indicated that while 30 min is an acceptable interval for exposure
      assessment, 15 min optimizes precision and practicality by ensuring that 95% of
      all observations differ less than ten percentage points from the "true" values.
      TVEA is a useful exposure assessment tool for the dynamic construction
      environment. It is flexible in that only those determinants that are of interest
      need be coded and the coding interval can be adjusted to accommodate the level of
      precision desired.

PMID- 15742712
TI  - Characterization of mold and moisture indicators in the home.
AB  - As studies increasingly support the presence of health risks associated with mold
      and moisture, understanding fungal concentrations and physical measurements as
      they relate to the microenvironment becomes more important. We conducted a cross
      sectional study in the homes of 64 subjects. The primary objective of this study
      was to use trained inspectors' list of indicators in rooms (bathroom, bedroom,
      and basement) and determine whether these indicators are associated with higher
      fungal levels or physical measurements. A new category for combining the
      concentrations of fungal species, referred to as moisture indicator fungi (MIF),
      is used in the analysis. Our results show that basements with a musty odor,
      efflorescence, water sources, or mold have a two- to threefold increase in fungal
      concentrations over basements without these indicators. The regression model for
      the basement was highly predictive of indoor MIF concentrations (r2 = .446, p =
      .017). Basement water sources are substantial predictors of indoor total fungi,
      MIF, and Aspergillus/Penicillium spp. MIF concentrations are higher in homes with
      basement water sources, and most notably, the increase in MIF concentrations is
      significant in other living spaces (bathroom and bedroom) of the dwelling.
      Basement water sources are important moisture/mold indicators for epidemiologists
      to use in exposure assessments performed in residential dwellings.

PMID- 15742715
TI  - Spatiotemporal Hopfield neural cube for diagnosing recurrent nasal papilloma.
AB  - Gadolinium-enhanced magnetic resonance imaging (MRI) is widely used to detect
      recurrent nasal tumours. A specifically designed two-layer Hopfield neural
      network, called the spatiotemporal Hopfield neural cube (SHNC), is presented, to
      be used for detecting recurrent nasal papilloma. Differing from conventional, two
      dimensional Hopfield neural networks, the SHNC extends the one-layer, two
      dimensional Hopfield network in the original image plane into a two-layer, three
      dimensional (3D) Hopfield network with pixel classification implemented in its
      third dimension. With extended 3D architecture, the network is able to use each
      pixel's spatial information in a pixel labelling procedure. Because the SHNC
      takes pixel spatial information into consideration, the effects of tiny detail or
      noise are removed. As a result, the drawback of disconnected fractions can be
      avoided. Furthermore, owing to the incorporation of competitive learning rules to
      update neuron states, to avoid the problem of having to satisfy strong
      constraints, the convergence of the network was improved. In addition, a more
      accurate signal-time curve, the relative intensity change (RIC), was adopted to
      represent the gadolinium-enhanced MRI temporal information, and the RIC curves of
      recurrent nasal papilloma were incorporated into the SHNC. The experimental
      results showed that the SHNC could obtain a more appropriate, precise position of
      recurrent nasal papilloma than the k-means, principal components analysis (PCA)
      or Eigenimage-filtering methods. The average sensitivity and specificity of the
      26 cases were 0.9998 and 0.9961, respectively. These values demonstrate the
      effectiveness of the proposed technique.

PMID- 15742713
TI  - Robot-aided neurorehabilitation of the upper extremities.
AB  - Task-oriented repetitive movements can improve muscle strength and movement co
      ordination in patients with impairments due to neurological lesions. The
      application of robotics and automation technology can serve to assist, enhance,
      evaluate and document the rehabilitation of movements. The paper provides an
      overview of existing devices that can support movement therapy of the upper
      extremities in subjects with neurological pathologies. The devices are critically
      compared with respect to technical function, clinical applicability, and, if they
      exist, clinical outcomes.

PMID- 15742717
TI  - Space-frequency quantiser design for ultrasound image compression based on
      minimum description length criterion.
AB  - The paper addresses the problem of how the spatial quantisation mode and subband
      adaptive uniform scalar quantiser can be jointly optimised in the minimum
      description length (MDL) framework for compression of ultrasound images. It has
      been shown that the statistics of wavelet coefficients in the medical ultrasound
      (US) image can be better approximated by the generalised Student t-distribution.
      By combining these statistics with the operational rate-distortion (RD)
      criterion, a space-frequency quantiser (SFQ) called the MDL-SFQ was designed,
      which used an efficient zero-tree quantisation technique for zeroing out the tree
      structured sets of wavelet coefficients and an adaptive scalar quantiser to
      quantise the non-zero coefficients. The algorithm used the statistical 'variance
      of quantisation error' to achieve the different bit-rates ranging from near
      lossless to lossy compression. Experimental results showed that the proposed
      coder outperformed the set partitioning in hierarchical trees (SPIHT) image coder
      both quantitatively and qualitatively. It yielded an improved compression
      performance of 1.01 dB over the best zero-tree based coder SPIHIT at 0.25 bits
      per pixel when averaged over five ultrasound images.

PMID- 15742714
TI  - Accuracy assessment of human trunk surface 3D reconstructions from an optical
      digitising system.
AB  - The lack of reliable techniques to follow up scoliotic deformity from the
      external asymmetry of the trunk leads to a general use of X-rays and indices of
      spinal deformity. Young adolescents with idiopathic scoliosis need intensive
      follow-ups for many years and, consequently, they are repeatedly exposed to
      ionising radiation, which is hazardous to their long-term health. Furthermore,
      treatments attempt to improve both spinal and surface deformities, but internal
      indices do not describe the external asymmetry. The purpose of this study was to
      assess a commercial, optical 3D digitising system for the 3D reconstruction of
      the entire trunk for clinical assessment of external asymmetry. The resulting
      surface is a textured, high-density polygonal mesh. The accuracy assessment was
      based on repeated reconstructions of a manikin with markers fixed on it. The
      average normal distance between the reconstructed surfaces and the reference data
      (markers measured with CMM) was 1.1 +/- 0.9 mm.

PMID- 15742718
TI  - Numerical simulation of thermal disposition with induction heating used for
      oncological hyperthermic treatment.
AB  - Hyperthermia plays an important role in oncological therapies, most often being
      used in combination with radiotherapy, chemotherapy and immunotherapy. The
      success of this therapy is strongly dependent on the precision and control of
      thermal deposition. Hyperthermia based on induction heating, with thermally self
      regulating thermoseeds inserted into the tumorous mass, is used for interstitial
      treatment. The technique was the subject of the numerical study presented in the
      paper. The analysis was carried out using coupled electromagnetic heating and
      thermo-fluid dynamic FEM simulations. During thermal deposition by induction
      heating of inserted seeds, the simulations estimated the thermal field inside and
      outside the tumour, as well as the sensitivity of the thermal field to variations
      regarding seed temperature, configuration and proximity to vessels. The method,
      for which accurate anatomical patient's information is essential, is suitable for
      providing useful qualitative and quantitative information about thermal
      transients and power density distribution for hyperthermic treatment. Several
      grid steps were analysed and compared. A 1 cm seed grid was resulted in good
      homogeneity and effectiveness of the thermal deposition. The cold spot effect
      caused by large vessels was demonstrated and quantified. Simulations of the
      heating of a tumorous mass in the liver showed that an indcutor generator
      operating at 200 kHz frequency and 500 A current, producing a pulsating magnetic
      field of H = 60 A cm(-1), was adequate for the treatment. The seeds that perform
      best among those tested (Nicu (28% Cu), PdNi (27.2% Ni), PdCo (6.15% Co) and
      ferrite core) were the PdNi (1 mm radius, 10 mm length), as they have a low Curie
      temperature (52 degrees C), which is the closest to the desired treatment
      temperature and thus reduces the risk of hot spots.

PMID- 15742716
TI  - Feasibility study of the use of similarity maps in the evaluation of oncological
      dynamic positron emission tomography images.
AB  - A preliminary study is presented on the potential role of similarity mapping (SM)
      in the evaluation of oncological dynamic 18F-fluorodeoxyglucose positron emission
      tomography studies, mainly in lesion localisation and detectability. Similarity
      maps were calculated using previously described (correlation coefficient (COR)
      and normalised correlation coefficient (NCOR)) and newly introduced similarity
      measures (sum of squares coefficient (SSQ), squared sum coefficient (SQS), sum of
      cubes coefficient (SC) and cubed sum coefficient (CS)). The results were
      evaluated using simulated and clinical data. The study revealed that the best
      suited similarity measure for such applications was the CS similarity
      coefficient, which provided the best parametric images, delineating structures of
      interest and supporting the visual interpretation of data sets. It was shown that
      SM and standardised uptake value (SUV) images had comparable diagnostic
      performance, although SM was able to offer additional time-related information in
      a single image. For the case of colorectal recurrences (17 cases), the measured
      contrast values for the CS and SUV images were 2.36 +/- 0.47 and 4.12 +/- 0.42,
      respectively, whereas, for three cases of giant cell tumours, these values were
      11.6 +/- 2.1 and 11.9 +/- 1.8, respectively.

PMID- 15742719
TI  - Modelling encapsulation tissue around cochlear implant electrodes.
AB  - The objective of the study was to explore the effect of electrode encapsulation
      by fibrous scar tissue on electrical potential distributions and auditory nerve
      fibre excitation patterns. A finite element model in combination with an auditory
      nerve fibre model was used to predict changes in threshold currents and auditory
      nerve fibre excitation patterns. The model showed that electrical potentials at
      the target nerve fibres and the electrode contacts changed in the presence of
      encapsulation tissue. This led to changes in threshold currents and spread of
      excitation. The effect of electrode encapsulation on threshold currents and
      spread of excitation depended on the thickness of the perilymph layer separating
      the fibrous tissue encapsulation and the electrode array, nerve fibre survival
      status, electrode geometry and configuration, and array location. Model results
      suggested that arrays located close to the modiolus were most sensitive to
      threshold changes caused by electrode encapsulation (changes were between -0.26
      and 2.41 dB), whereas encapsulation of an electrode array had less effect on
      threshold currents when the array was located in a lateral position in the scala
      tympani (changes were between -0.64 and 1.5 dB). For medially located arrays,
      changes in the spread of excitation varied between an increase of 0.21 mm and a
      decrease of 0.33 mm along the length of the basilar membrane, and an increase of
      0.18 mm and a decrease of 0.66 mm along the length of the basilar membrane were
      calculated for laterally located arrays.

PMID- 15742720
TI  - Computerised analysis of auscultatory sounds associated with vascular patency of
      haemodialysis access.
AB  - Vascular access for renal dialysis is a lifeline for about 120 000 individuals in
      the United States. Stethoscope auscultation of vascular sounds has some utility
      in the assessment of access patency, yet can be highly skill-dependent. The
      objective of the study was to identify acoustic parameters that are related to
      changes in vascular access patency. The underlying hypothesis is that stenoses of
      haemodialysis access vessels or grafts cause vascular sound changes that are
      detectable using computerised data acquisition and analysis. Eleven patients
      participated in the study. Their vascular sounds were recorded before and after
      angiography, which was accompanied by angioplasty in most patients. The sounds
      were acquired using two electronic stethoscopes and then digitised and analysed
      on a personal computer. Vessel stenosis changes were found to be associated with
      changes in acoustic amplitude and/or spectral energy distribution. Certain
      acoustic parameters correlated well (correlation coefficient = 0.98, p < 0.0001)
      with the change in the degree of stenosis, suggesting that stenosis severity may
      be predictable from these parameters. Parameters also appeared to be sensitive to
      modest diameter changes (> 20%), (p < 0.005, Wilcoxon rank sum test). These
      results suggest that computerised analysis of vascular sounds may be useful in
      vessel patency surveillance. Further testing using longitudinal studies may be
      warranted.

PMID- 15742710
TI  - Use of a directional spray system design to control respirable dust and face gas
      concentrations around a continuous mining machine.
AB  - A laboratory study assessed the impacts of water spray pressure, face ventilation
      quantity, and line brattice setback distance on respirable dust and SF6 tracer
      gas concentrations around a continuous mining machine using a sprayfan or
      directional spray system. Dust levels were measured at locations representing the
      mining machine operator and the standard and off-standard shuttle car operators,
      and in the return airway. The results showed that changes in all three
      independent variables significantly affected log-transformed dust levels at the
      three operator sampling locations. Changes in setback distance impacted return
      airway dust levels. Laboratory testing also identified numerous variable
      interactions affecting dust levels. Tracer gas levels were measured on the left
      and right sides of the cutting drum and in the return. Untransformed gas levels
      around the cutting drum were significantly affected by changes in water pressure,
      face ventilation quantity, and setback distance. Only a few interactions were
      identified that significantly affected these concentrations. Gas levels in the
      return airway were grouped by face ventilation quantity. Return gas levels
      measured at the low curtain quantity were generally unaffected by changes in
      water pressure or curtain setback distance. At the high curtain quantity, return
      airway gas levels were affected by curtain setback distance. A field study was
      conducted to assess the impact of these parameters in an actual mining operation.
      These data showed that respirable dust levels may have been impacted by a change
      in water pressure and, to a lesser extent, by an increase in curtain setback
      distance. A series of tracer gas pulse tests were also conducted during this
      study. The results showed that effectiveness of the face ventilation was impacted
      by changes in curtain flow quantity and setback distance. Laboratory testing
      supported similar conclusions.

PMID- 15742721
TI  - Simultaneous estimation of muscle fibre conduction velocity and muscle fibre
      orientation using 2D multichannel surface electromyogram.
AB  - The paper presents a new approach for simultaneous estimation of muscle fibre
      conduction velocity (MFCV) and muscle fibre orientation (MFO) for motor units
      (MUs) in two-dimensional (2D) multichannel surface electromyography recordings.
      This is an important tool for detecting changes and abnormalities in muscle
      function and structure. In addition, simultaneous estimation of MFO and MFCV
      avoids the necessity of manual electrode alignment. The proposed method detected
      propagating MU action potentials (MUAPs) in a running time window as moving
      components in amplitude maps. Thereafter, estimations were obtained by fitting a
      three-dimensional function to these maps. The performance was evaluated using
      synthetic MU signals at 10 dB SNR and authentic biceps brachii measurements.
      Results demonstrated MFCV and MFO estimates with standard deviations of less than
      0.05 m s(-1) and 1 degrees for simulated signals, and less than 0.2 m s(-1) and 4
      degrees for experimental data. However, standard deviations as low as 0.12 m s(
      1) and 1.6 degrees from real signals were demonstrated. It was concluded that the
      method performs as well as, or better than, linear array multichannel methods
      when individual propagating MUAPs can be identified, even if electrodes are not
      aligned with fibre direction.

PMID- 15742722
TI  - Hydrocephalus shunts and waves of intracranial pressure.
AB  - The majority of contemporary hydrocephalus valves are designed to introduce a low
      resistance to flow into the cerebrospinal fluid (CSF) drainage pathway, and an
      therefore intended to stabilise intracranial pressure (ICP) at a level close to
      the shunt's operating pressure. However, this goal cannot always be attained.
      Accelerated CSF drainage with vertical body posture in ventriculo-peritoneal
      shunts is one reason for the ICP decreasing below the shunt's operating pressure.
      Another possible factor has been studied: the impact of the pulsating pattern in
      the ICP on the operating pressure. Six popular constructions of medium-pressure
      valves were studied (Radionics Low-profile, Delta, Hakim Precision, Holter,
      Integra In-line and Hakim NMT). Valves were mounted in the testing rig in the UK.
      Shunt Evaluation Laboratory and perfused with de-ionised water at a rate of 0.3
      ml min(-1), and proximal pulsating pressures of different amplitudes (from 2 to
      30mmHg peak-to-peak) and frequencies (70-10 cycles min(-1)) were superimposed.
      Laboratory findings were compared with clinical material containing recordings of
      ICP made in patients to diagnose reasons for ventriculomegaly. The mean operating
      pressure decreased in all valves when the simulated amplitude of heart pulsations
      increased. The rate of this decrease was dependent on the type of valve (variable
      from 2.5 to 5 mm Hg per increase in peak-to-peak amplitude by 10 mm Hg). The
      decrease was not related to the frequency of the wave. The relationship between
      pulse amplitude and ICP in 35 patients with blocked shunts was strong (R = 0.48;
      p < 0.03; slope 0.14) and in 25 patients with properly functioning shunts was non
      significant (R = 0.057; p = 0.765). Two examples of decrease in mean ICP in the
      presence of increased vasogenic ICP waves in shunted patients are presented. The
      shunt operating pressure, which 'sets' the ICP in shunted patients may be
      influenced by the dynamics of a patient's ICP waveform.

PMID- 15742723
TI  - Validation of an accelerometer for determination of muscle belly radial
      displacement.
AB  - A commercial variable-capacitance micromachined accelerometer was validated for
      muscle belly radial displacement measurement. The displacement was calculated by
      the acceleration data being integrated twice and was compared with the results
      obtained simultaneously by an accurate mechanical displacement sensor based on an
      optical encoder. The aim of the investigation was to evaluate the accuracy and
      precision of an accelerometer for tensiomyography, which is a method for the
      detection of skeletal muscle contractile properties on the basis of muscle belly
      radial displacement. A hundred measurements at a bandwidth of 2300 Hz were
      performed. It was shown that the accuracy and precision in determination of the
      maximum displacement and the time of the maximum displacement from the calculated
      curve were satisfactory, in spite of the standard deviation of the twice
      integrated acceleration growing approximately linearly with time. The results
      were accurate enough since the elapsed time from the beginning of the integration
      was small (less than 75 ms). The measured maximum displacement ranges were
      between 9.2 and 10.2 mm. The mean relative error was less than 1% (SD = 0.02mm)
      for the maximum displacement and about 1% (SD = 0.6 ms) for the time to maximum
      displacement. The accuracy of the half-relaxation time determination was more
      uncertain because of the relatively high relative error of -2.4% (SD = 3 ms).
      Results showed that a commercial micromachined accelerometer could be suitable
      for the measurement of muscle belly radial displacement and used for development
      of a future miniaturised and flexible system for the measurement of similar
      displacements.

PMID- 15742725
TI  - Quaternion-based strap-down integration method for applications of inertial
      sensing to gait analysis.
AB  - The proposed strap-down integration method exploits the cyclical nature of human
      gait: during the gait swing phase, the quaternion-based attitude representation
      is integrated using a gyroscope from initial conditions that are determined
      during stance by an accelerometer. Positioning requires double time integration
      of the gravity-compensated accelerometer signals during swing. An interpolation
      technique applied to attitude quaternions was developed to improve the accuracy
      of orientation and positioning estimates by accounting for the effect of sensor
      bias and scale factor drifts. A simulation environment was developed for the
      analysis and testing of the proposed algorithm on a synthetic movement
      trajectory. The aim was to define the true attitude and positioning used in the
      computation of estimation errors. By thermal modelling, the changes of bias and
      scale factor of the inertial sensors, calibrated at a single reference
      temperature, were analysed over a range of +/- 10 degrees C, for measurement
      noise standard deviations up to sigma(g) = 2.5 degrees s(-1) (gyroscope) and
      sigma(a) = 0.05 m s(-2) (accelerometer). The compensation technique reduced the
      maximum root mean square errors (RMSEs) to: RMSE(theta) = 14.6 degrees
      (orientation) and RMSE(d) = 17.7cm (positioning) for an integration interval of
      one gait cycle (an improvement of 3 degrees and 7 cm); RMSE(theta) = 14.8 degrees
      and RMSE(d) = 30.0 cm for an integration interval of two gait cycles (an
      improvement of 11 degrees and 262 cm).

PMID- 15742726
TI  - Kinematic study of a reconstructed hip in paediatric oncology.
AB  - In 1997, a large portion of the femur of a four-year-old child affected by a
      Ewing's sarcoma was reconstructed with an innovative technique that used a
      massive bone allograft, in conjunction with a vascularised fibula autograft that
      was directly articulated within the acetabulum. The aim of the present study was
      to assess the kinematic behaviour of the reconstructed hip during flexion, once
      the acute remodelling process observed after the operation had ceased. A few
      additional CT slices of the hip joint region, in a flexed position, were taken at
      month 33 of the follow-up. The helical axes relative to the neutral-flexion motor
      action were estimated: their relative positions, with respect to the anatomical
      femoral heads, were compared, and the translation of the anatomical head centres
      was estimated. The angles spanned by the two femurs were almost equal, as were
      the translations along the respective helical axis. The main difference between
      the two femurs was the distance between the estimated femoral head centres and
      the relative helical axes. This resulted in a non-negligible translation of 2.9
      mm of the fibula head inside the acetabulum during flexion, significantly higher
      than the 0.5 mm found for the intact contralateral femur. The results showed
      that, although the transplanted fibula grew and remodelled during the follow up,
      the action of the reconstructed hip joint still cannot be described as a ball-and
      socket.

PMID- 15742724
TI  - Vector projection of biomagnetic fields.
AB  - Biomagnetic measurements are increasingly popular as functional imaging
      techniques for the non-invasive assessment of electrically active tissue.
      Although most currently available magnetometers utilise only one component of the
      vector magnetic field, some studies have suggested the possibility of obtaining
      additional information from recordings of the full magnetic field vector. Three
      projection techniques were applied to different biomagnetic signals for analysis
      of the three orthogonal components of the vector magnetic field. Vector magnetic
      fields obtained from fetal cardiac activity were projected into evenly spaced
      directions around a unit sphere. The vector magnetic field recorded from multiple
      intestinal current sources with independent temporal frequencies was then
      projected. Finally, an external reference signal from an invasive electrode was
      used to project the recorded vector magnetic fields due to gastric electrical
      activity. In each case, it was found that the information obtained by examination
      of the projected magnetic field vectors gave superior clinical insight to that
      obtained by analysis of any single magnetic field component.

PMID- 15742727
TI  - Human standing posture control system depending on adopted strategies.
AB  - Control of the standing posture of humans involves at least two distinct modes of
      operation to restore the body balance in the sagittal plane: the ankle strategy
      and the hip strategy. The objective of the study was to estimate the contribution
      of vestibular, visual and somatosensory feedbacks to these distinct strategies.
      The body dynamics was described as the motion of two linked rigid segments that
      represented the legs and the rest of the body. The posture controller received
      the inclination angles of the two body segments as inputs and regulated the
      moments around the ankle and hip joints. The controller had four feedback paths
      that were characterised by transfer functions connecting the two inputs and the
      two outputs. To evoke the distinct strategies, the floor conditions were varied
      by narrowing the support surface under the feet. A continuous pseudo-random
      external disturbing force was applied to the waist and the thigh independently.
      The inclination angles of the body segments and the ground reaction force were
      measured, and the transfer functions of the controller were estimated with the
      maximum-likelihood system identification procedure. Six healthy male adult
      subjects participated in the experiment. When the hip strategy became evident
      under the narrow support surface conditions, the transfer function relating the
      leg inclination angle and the ankle joint moment decreased its DC gain (16%),
      whereas the other three transfer functions increased the gains (20-140%) (ANOVA,
      p < 0.05). Based on a criterion for simplicity in the modification of the posture
      controller, these changes suggest a new hypothesis that, when posture control
      becomes difficult, the central nervous system selectively activates the
      somatosensory feedback paths from the hip joint angle to the moments around the
      ankle and hip joints.

PMID- 15742728
TI  - Robot-assisted fracture reduction: a preliminary study in the femur shaft.
AB  - Reduction in femoral shaft fractures can be difficult to achieve with minimally
      invasive techniques. Malalignment and high intra-operative radiation exposure can
      result. The hypothesis was that robot-assisted fracture reduction could improve
      the quality of reduction while reducing the amount of radiation exposure. A robot
      system was developed that allows fracture manipulation with a joystick as input
      device. The system provides the surgeon with haptic and metric feedback. Fifteen
      synthetic femurs were broken and reduced by simulated open (group A) and closed
      techniques (group B). These techniques were compared with the robot-assisted
      reduction with (group C) and without (group D) haptic and metric information. An
      image intensifier was simulated with two orthogonal cameras. All reduction
      techniques showed minor malalignment. In group C, the alignment was:
      procurvatum/recurvatum 0.6 degrees (0-2.0 degrees); varus/valgus 0.8 degrees (0
      3.0 degrees); and axial rotation 0.8 degrees (0-3.1 degrees). A significant
      difference was seen between the groups (two-way ANOVA, p < 0.001). Axial rotation
      was significantly lower in group C than in group B (1.9 degrees; p < 0.001). The
      residual varus and valgus deviation was higher in group C compared with group A
      (0.4 degrees, p = 0.03). The median number of simulated radiographs was
      significantly less in group C (35) compared with group D (72; p < 0.001) and
      group B (49; p = 0.01). Robot-assisted fracture reduction of the femur provides
      high precision in alignment while reducing the amount of intraoperative imaging.
      Further research in this field is worthwhile.

PMID- 15742729
TI  - Robust design of finger probe in non-invasive total haemoglobin monitor.
AB  - The development of a non-invasive monitor of total haemoglobin has been reported
      previously. The paper presents the design and testing of a finger probe used in
      that optical haemoglobin monitor. When a finger is inserted into the probe, light
      is radiated onto the nail, and a silicon detector measures transmitted light.
      This finger probe can have different values or settings for design parameters
      such as the internal colour, detector area, the emission area of a light source
      and the distance between the light source and detector. Design of experiment
      (DOE) was introduced to select the best combination of design parameters that
      were robust to external conditions such as finger alignment and ambient light. An
      optimally designed finger probe from DOE analysis, compared with the initial
      design, increased the correlation coefficient from 0.696 to 0.869 and improved
      the standard deviation from 1.18 to 0.81 g dl(-1) in predicting total
      haemoglobin. This was under different conditions of finger-probe alignment. Under
      different ambient light conditions, the optimum design improved the correlation
      coefficient from 0.735 to 0.870 and reduced the standard deviation from 1.14 to
      0.83 g dl(-1).

PMID- 15742730
TI  - Sprouting from arteriovenous shunt vessels with increased blood flow.
AB  - The purpose of this study was to evaluate the effect of increased blood flow on
      angiogenesis at the large vessels. The arteriovenous (AV) shunt was made on the
      thigh of male Wistar rats (n = 27) to increase blood flow, wrapped with
      artificial skin dermis, which consisted of a silicon outer layer, and isolated
      from surrounding tissues. Blood flow increased from 2.40 +/- 0.77 to 35.8 +/- 8.7
      ml min(-1) (14.9 times), and the shear stress index (relative value of shear
      stress) increased from 10.7 +/- 3.6 to 73.4 +/- 18.1 (6.85 times) 60 min after
      the shunt formation. Newly formed vessels were observed around the AV shunt loop.
      Scanning electron micrographs at the AV shunt vessel lumen showed modified
      endothelial cells at day 7 and a remarkable number of pores at day 14. The volume
      of newly formed vessels was increased 12 times from day 5 to day 14. The
      mechanical factor of shear stress was considered the major stimulator of
      angiogenesis. This is the first report of electron-microscopic observation of
      sprouts from a large vessel lumen. The new AV shunt model is useful for basic
      research on angiogenesis at the large vessels in vivo and, furthermore, could
      generate vascularised tissues with various cultured cells.

PMID- 15742731
TI  - Non-invasive measurement of systolic blood pressure on the arm utilising
      photoplethysmography: development of the methodology.
AB  - Photoplethysmography (PPG) can be used to measure systolic blood pressure at the
      brachial artery. With a specially designed probe, positioned in the most distal
      position beneath a pressure cuff on the upper arm, this is possible. The distance
      between the light source (880 nm) and the photodetector was 20 mm. A test was
      performed on neuro-intensive care patients by determining blood pressure from the
      PPG curves, and, when it was compared with systolic blood pressure obtained from
      inserted indwelling arterial catheters, a correlation factor of r = 0.95 was
      achieved. The difference between blood pressure obtained using PPG and invasive
      blood pressure measurement was 3.9 +/- 9.1 mmHg (mean +/- SD), n = 19. The depth
      to the brachial artery was 13.9 +/- 4.1 mm (mean +/- SD), n = 18. A digital PPG
      system utilising pulsating light was also developed.

PMID- 15742732
TI  - Optimum control of the Hemopump as a left-ventricular assist device.
AB  - A general framework for designing an optimum control strategy for the Hemopump is
      described. An objective function was defined that includes four membership
      functions, each constructed based on the desired values of one of the four
      members: stroke volume, mean left atrial pressure, aortic diastolic pressure and
      mean pump rotation speed. The Hemopump was allowed to operate either at a
      constant speed or at two different speeds during a cardiac cycle. The goal was to
      maximise the objective function by varying the magnitude and timing of the pump
      speed. Using a canine circulatory model, it was demonstrated that, in general,
      different cardiac conditions or different clinical objectives require different
      operation parameters. For example, when a left ventricle with minor ischaemia was
      simulated, and the main objective was to increase stoke volume, the objective
      function was maximised, from a value of 0.877 when the pump was off, to 0.946
      when the pump was operated at speed 2 (18 500 revolutions min(-1)). On the other
      hand, for a severely ischaemic heart, the optimum pump speed became speed 3 (20
      000 revolutions min(-1)), which maximized the objective function to 0.943 (from
      0.707 when the pump was off). The results also suggest that it is more beneficial
      to operate the Hemopump at two different speeds during a cardiac cycle (a higher
      speed during systole and early diastole, and a lower speed during late diastole)
      than to maintain a constant speed throughout the cardiac cycle.

PMID- 15742733
TI  - Non-linear analysis of the electroencephalogram for detecting effects of low
      level electromagnetic fields.
AB  - The study compared traditional spectral analysis and a new scale-invariant
      method, the analysis of the length distribution of low-variability periods
      (LDLVPs), to distinguish between electro-encephalogram (EEG) signals with and
      without a weak stressor, a low-level modulated microwave field. During the
      experiment, 23 healthy volunteers were exposed to a microwave (450 MHz) of 7 Hz
      frequency on-off modulation. The field power density at the scalp was 0.16 mW cm(
      2). The experimental protocol consisted of ten cycles of repetitive microwave
      exposure. Signals from frontal EEG channels FP1 and FP2 were analysed. Smooth
      power spectrum and length distribution curves of low-variability periods, as well
      as probability distribution close to normal, confirmed that stationarity of the
      EEG signal during recordings was achieved. The quantitative measure of LDLVPs
      provided a significant detection of the effect of the stressor for the six
      subjects exposed to the microwave field but for none of the sham recordings. The
      spectral analysis revealed a significant result for one subject only. A
      significant effect of the exposure to the EEG signal was detected in 25% of
      subjects, with microwave exposure increasing EEG variability. The effect was not
      detectable by power spectral measures.

PMID- 15742734
TI  - Couplet alignment and improved electrofusion by dielectrophoresis for a zona-free
      high-throughput cloned embryo production system.
AB  - Mammalian cloning by somatic nuclear transfer has great potential for developing
      medical applications such as biopharmaceuticals and generation of tissues for
      transplantation. For agricultural applications, it allows the rapid dissemination
      of genetic gain in livestock breeding. The maximisation of that potential
      requires improvements to overall cloning technology, especially with respect to
      increasing cloning efficiency and throughput rates in cloned embryo production. A
      zona-free embryo reconstruction system was developed to increase cloning
      throughput and ease of operation. Central to this system is a modified
      electrofusion procedure for nuclear transfer. Cytoplast-donor cell couplets were
      placed in a custom-designed 'parallel plate' electrode chamber. A 1 MHz
      sinusoidal AC dielectrophoresis alignment electric field of 6-10 kV m(-1) was
      applied for 5-10s. The couplets were then fused using 2 x 10 micros rectangular
      DC-field pulses (150-200 kV m(-1)), followed by application of the AC field (6-10
      kV m(-1)) for another 5-10 s. Fusion was performed in hypoosmolar buffer (210
      mOsm). Automated alignment of up to 20 couplets at a time has been achieved,
      resulting in greatly improved fusion throughput rates (2.5-fold increase) and
      improved fusion yields (1.3-fold increase), compared with commonly followed zona
      intact protocols.

PMID- 15742735
TI  - Three-dimensional cell cycle model with distributed transcription and
      translation.
AB  - A computational cell cycle model that can describe three state properties, cell
      maturation age, specific mRNA and protein content, has been developed. Cell cycle
      progression is monitored by maturation age, and population heterogeneity is
      generated by the introduction of a probable random event embedded in the G1
      phase. Specific mRNA is generated with a constant transcription rate at the
      single-cell level, and its turnover is governed by a first-order decay.
      Translation is modelled as a first-order dependence on the transcripts, and the
      protein product is subsequently exported. Dynamic chemostat simulations are used
      to demonstrate the ability of the model to track evolving parent and daughter
      subpopulations in maturation and cellular contents. The cell subpopulations
      eventually converge to an equilibrium distribution corresponding to the steady
      state of a chemostat, and halving of cellular content at cell division is the
      dominant driving force leading towards the population equilibrium state.

PMID- 15742742
TI  - What was the most difficult encounter you've had with a doctor?

PMID- 15742736
TI  - In vitro validation of some flow assumptions for the prediction of the pressure
      distribution during obstructive sleep apnoea.
AB  - An adequate description of the pressure distribution exerted by the fluid flow on
      pharyngeal walls is a first requirement to enhance the understanding, modelling
      and, consequently, the prediction of airway collapse during obstructive sleep
      apnoea. From a fluid mechanical point of view, several flow assumptions can be
      formulated to reduce the governing flow equations. The relevance of some major
      flow assumptions and the accuracy of the resulting flow description with respect
      to obstructive sleep apnoea was investigated on a rigid geometrical replica of
      the pharynx. Special attention was given to the influence of geometrical
      asymmetry and to the position of the flow separation point. An in vitro
      experimental and theoretical study of steady pharyngeal fluid flow is presented
      for different constriction heights and upstream pressures. Pressure and velocity
      distributions along a rigid in vitro replica of the oro-pharyngeal cavity were
      compared with different flow predictions based on various assumptions. Fluid flow
      models were tested for volume flow rates ranging from 5 to 120 1 min(-1) and for
      minimum apertures between 1.45 and 3.00 mm. Two-dimensional flow models were
      required and predicted experimental results with an accuracy of 15%. Flow
      theories classically used in the case of a Starling resistor provided poor
      agreement.

PMID- 15742745
TI  - How to make sense of clinical research.

PMID- 15742746
TI  - Meeting the challenge of Alzheimer's care.

PMID- 15742747
TI  - Patient information. When someone you love has Alzheimer's.

PMID- 15742749
TI  - Disabilities don't stop these nurses. Interview by Barbara Weiss.

PMID- 15742750
TI  - Government's EMR Project yet to net seed money.

PMID- 15742748
TI  - 2 devices that unclog feeding tubes.

PMID- 15742751
TI  - Health plans strain to contain rapidly rising cost of imaging.

PMID- 15742752
TI  - Breast cancer screening. Some plans do better than others.

PMID- 15742753
TI  - Health plans slow to adopt outpatient prospective payment.

PMID- 15742754
TI  - The comeback kid. Harvard Pilgrim Health Care.

PMID- 15742755
TI  - P4P: transitional at best.

PMID- 15742756
TI  - Is it time to create a 'fed board' to oversee clinical research?

PMID- 15742757
TI  - Drug-development process already subject to oversight.

PMID- 15742758
TI  - A new approach for MS.

PMID- 15742759
TI  - Statistics in clinical practice.

PMID- 15742760
TI  - Visualization of a transtympanic ossicular prosthesis.

PMID- 15742761
TI  - Endoscopic view of a clival skull base tumor invading the sphenoid space.

PMID- 15742762
TI  - Visualization of the hyoid bone with laryngeal endoscopy.

PMID- 15742763
TI  - Labyrinthitis ossificans associated with sensorineural deafness.

PMID- 15742764
TI  - Recreating the alar crease following melolabial flap reconstruction of a full
      thickness alar defect.

PMID- 15742765
TI  - Sarcoidosis.

PMID- 15742766
TI  - A rare case of rapidly progressive craniofacial chondrosarcoma.

PMID- 15742767
TI  - Establishing a practice's financial policies.

PMID- 15742768
TI  - Efficacy of the Epley maneuver for posterior canal BPPV: a long-term, controlled
      study of 81 patients.
AB  - We assessed the efficacy of the Epley maneuver (canalith repositioning) in a
      study of 81 patients with posterior semicircular canal benign paroxysmal
      positional vertigo (BPPV). A group of 61 patients underwent the maneuver, while a
      control group of 20 patients received no therapy. All patients were evaluated at
      1 and 6 months. The percentage of patients who experienced subjective improvement
      was significantly higher in the treatment group at both 1 month (89% vs. 10%) and
      6 months (92% vs. 50%). Three patients in the treatment group who did not improve
      after treatment underwent a second maneuver, and all achieved a positive result.
      In addition, 4 successfully treated patients experienced a recurrence between 1
      and 6 months following treatment; 3 were retreated, and 2 of them responded well.
      We conclude that the Epley maneuver provides effective and long-term control of
      symptoms in patients with BPPV.

PMID- 15742769
TI  - Primary care approach to hearing loss: the hidden disability.
AB  - We report the results of a survey designed to investigate audiologic referral
      patterns of primary care physicians and, more specifically, their referral of
      patients for hearing aids and cochlear implants. Three hundred internal medicine
      and family medicine physicians were identified from a referral basin of a
      tertiary care center and chosen randomly to be faxed questionnaires concerning
      their views about patients with hearing loss, hearing loss screening and referral
      practices, and availability of local resources. Of the 260 physicians who
      received a questionnaire, 85 (32.7%) responded Of their communities (60% of which
      had populations of fewer than 50,000), 82.4% had an otolaryngologist and 40% had
      access to an academic center. Although 97.6% of the responding physicians
      indicated that hearing loss affected patients' quality of life, only 60% assessed
      patients for hearing loss. "Lack of time" and "more pressing issues" were the
      most common reasons given for not evaluating patients for hearing loss. Although
      76 physicians (89.4%) said they were aware of cochlear implants, only 22 (25.9%)
      had referred patients for implant evaluation. Lack of referral most commonly
      resulted from uncertainties about "where to refer" and "which patients were
      potential candidates." The results of this survey suggest that a large percentage
      of primary care physicians do not routinely test for hearing impairment in
      adults.

PMID- 15742770
TI  - Penetrating middle ear trauma: a report of 2 cases.
AB  - Penetrating middle ear injury can result in hearing loss, vertigo, and facial
      nerve injury. We describe the cases of 2 children with penetrating trauma to the
      right ear that resulted in ossicular chain disruption; one injury was caused by
      cotton-tipped swabs and the other by a wooden matchstick. Symptoms in both
      children included hearing loss and otalgia; in addition, one child experienced
      ataxia and the other vertigo. Physical examination in both cases revealed a
      perforation in the posterosuperior quadrant of the tympanic membrane and visible
      ossicles. Audiometry identified a moderate conductive hearing loss in one child
      and a mild sensorineural hearing loss in the other. Both children underwent
      middle ear exploration and reduction of a subluxed stapes. We discuss the
      diagnosis, causes, and management of penetrating middle ear trauma. To reduce the
      morbidity associated with these traumas, otologic surgeons should act promptly
      and be versatile in choosing methods of repairing ossicular chain injuries.

PMID- 15742771
TI  - Metastasis of colonic adenocarcinoma to the external ear canal: an unusual case
      with a complex-pattern of disease progression.
AB  - We report on a patient who developed far-ranging metastases of adenocarcinoma of
      the colon that followed a gradual cephalad progression, including the right
      external ear canal, and led to hearing loss. The patient was a 63-year-old white
      male with stage III adenocarcinoma of the colon. After 2 years with metastases
      elsewhere, he developed hearing loss on the right side. Physical examination of
      the head and neck showed a mass in the external ear canal, and biopsy confirmed
      adenocarcinoma. After removal, the patient's hearing improved. This case is
      interesting not only because of the unusual metastasis to the external ear canal,
      but also because of the patient's previous history of metastasis over the course
      of more than 2 years. The significance of such wide-ranging metastases is that
      metastasis of adenocarcinoma to the ear did not signal imminent death, and relief
      of the hearing loss it caused was possible.

PMID- 15742772
TI  - CSF otorrhea complicating temporal bone osteoradionecrosis in a patient with
      nasopharyngeal carcinoma.
AB  - A 44-year-old Chinese man with a history of nasopharyngeal carcinoma that was
      treated with radiotherapy presented with fluid in the middle ear. We performed a
      myringotomy and subsequently made a diagnosis of cerebrospinal fluid (CSF)
      leakage secondary to osteoradionecrosis of the temporal bone. To the best of our
      knowledge, this is only the second reported case of an otogenic CSF leak
      resulting from osteoradionecrosis of the temporal bone. This case highlights the
      controversial role of myringotomy in the management of CSF otorrhea.

PMID- 15742773
TI  - The effect of silver nitrate on nasal septal cartilage.
AB  - Epistaxis from the anterior septum is frequently treated with a topical
      application of silver nitrate, which cauterizes the bleeding vessel. However,
      this treatment causes a septal perforation in a small percentage of patients. We
      report our study of the histologic effect of topical silver nitrate on samples of
      septal tissue obtained from 11 patients. We found that 30 seconds of exposure
      allowed silver nitrate to penetrate to a depth of approximately 1 mm. Longer
      exposure (45 and 60 sec) resulted in no significant additional penetration.
      Similarly, the amount of silver nitrate deposition into the chondrocytic lacunae
      did not vary significantly with the length of exposure. On the other hand, the
      depth of deposition into the extracellular matrix was positively associated with
      the duration of exposure. We found no direct evidence that silver nitrate exerted
      any damaging effect on septal cartilage. Instead, the development of septal
      perforations in patients who receive topical silver nitrate may be attributable
      to necrosis of the septal cartilage following damage to the overlying
      perichondrium, from which it derives its blood supply.

PMID- 15742774
TI  - Primary columellar angiosarcoma: a case report.
AB  - Angiosarcoma of the head and neck, a rare malignancy, is associated with a high
      degree of invasiveness and poor survival. A high level of suspicion followed by
      histopathologic and immunohistochemical studies is warranted in order to arrive
      at a well-timed and accurate diagnosis. We report the case of a 56-year-old man
      who developed an unusually small neoplasm in the nasal columella. Rapid diagnosis
      allowed for simple treatment with surgical excision, a rare circumstance because
      most of these tumors require extensive surgery. Close long-term follow-up of
      patients with angiosarcoma of the head and neck is vitally important.

PMID- 15742775
TI  - Primary non-Hodgkin's lymphoma of the frontal sinus: case report and review of
      the literature.
AB  - Non-Hodgkin's lymphoma of the sinonasal tract is an uncommon lesion, representing
      1.5 to 15% of all lymphomas. Most cases of primary non-Hodgkin's lymphoma of the
      sinonasal tract occur in the maxillary sinus, ethmoid sinus, and nasal cavity;
      its occurrence in the frontal sinus is extremely rare. We report a case of
      primary type B non-Hodgkin's lymphoma of the frontal sinus in a 43-year-old man.
      The patient complained of frontal headaches that had not improved with analgesic
      drugs, and he presented with a frontal bulge that involved the left upper eyelid;
      the bulge had progressively enlarged over a 3-month period A biopsy of the mass
      identified the type B non-Hodgkin's lymphoma. Immunohistochemical study not only
      confirmed the histologic type of the tumor, it also provided some important
      information about the primary tumor site. Advances in immunohistochemistry have
      shown that type B non-Hodgkin's lymphoma is more common in North American and
      European patients, whereas subtype T is more common in Asians and in some Latin
      Americans. The treatment of this condition is still controversial, but the
      combination of radiotherapy and chemotherapy has yielded the best results in all
      stages of the disease.

PMID- 15742777
TI  - Why I got a master's degree.

PMID- 15742776
TI  - Extravascular papillary endothelial hyperplasia of the larynx: a case report and
      review of the literature.
AB  - Papillary endothelial hyperplasia (PEH), a tumor that falls along the spectrum of
      reactive to neoplastic vascular lesions, must be diagnosed carefully because it
      can resemble an angiosarcoma. PEH is generally considered to be the result of an
      unusual form of thrombus organization, exhibiting excessive papillary endothelial
      proliferation that is usually confined to the lumen of preexisting vessels or
      vascular malformations. Most cases of PEH are of the intravascular type;
      extravascular PEH is rare. We describe what we believe is the first reported case
      of an extravascular PEH in the larynx.

PMID- 15742778
TI  - Altered mental status: cause determines treatment.

PMID- 15742779
TI  - PA as exercise advocate: prescribing exercise for patients.

PMID- 15742780
TI  - Patient information from you physician assistant. Health benefits of exercise.

PMID- 15742781
TI  - Case studies in writing the exercise prescription.

PMID- 15742782
TI  - Liver transplantation: managing complications in primary care.

PMID- 15742783
TI  - Management of traumatic femoral shaft fractures.

PMID- 15742784
TI  - Evidence-based medicine? Show us the evidence!

PMID- 15742785
TI  - Case of the month. Concurrent diagnosis of lung cancer and tuberculosis.

PMID- 15742786
TI  - 'Blue man' throws ED into divert, cause remains unknown for 9 hours.
AB  - Don't ever assume your disaster plan is completed; continual review is essential.
      Make sure all ED staff, greeters, and patient reps know where your
      decontamination facilities are. Wherever possible, avoid exposing the patient to
      visitors and minimize staff contact. Inform quarantined individuals about the
      situation and symptoms they should look for.

PMID- 15742787
TI  - Unknown substance: when do you shut down?

PMID- 15742788
TI  - Uninsured children: an untapped revenue source?
AB  - Simple procedures and staff changes can yield new benefits to your department and
      hospital's bottom line. Simply handing out application forms can increase child
      enrollment by approximately 14%. Hiring a new, dedicated worker to enroll
      children will pay for itself many times over. Once children are enrolled,
      financial benefits grow over time with each return visit to your ED.

PMID- 15742789
TI  - Saving lives is more than 'virtual' with teletrauma.
AB  - Hooking up your ED to a regional system enhances the care your staff can give
      patients. With cameras and computers to guide distant experts, invaluable
      consults become possible. The number of patients who receive treatment within the
      golden hour increases dramatically. When transferring patients, the receiving
      facility has more detailed knowledge of the care you've given.

PMID- 15742790
TI  - Paperless system solves problem of lost chart costs.
AB  - Before going paperless, know what you're looking for and what the expected
      benefits are. The most technologically advanced system in the world is worthless
      if your doctors can't use it. The system will have greater value if your nurses
      can chart on it as well. A careful cost-benefit analysis should tell you ahead of
      time whether the system will pay for itself.

PMID- 15742791
TI  - '15-30' commitment key to reduced wait times.
AB  - Approach throughput as a continuous process. Explore all possible avenues for
      improvement. Adding another triage nurse and physician during peak hours can
      enhance fast-track care. The acquisition of additional telemetry beds, if
      financially feasible, can affect performance significantly. When evaluating
      results, consider the entire process, rather than focusing just on average wait
      time.

PMID- 15742792
TI  - If the Joint Commission surveyor doesn't understand how your ED is compliant,
      what should you do?
AB  - You can disagree with a surveyor, but the disagreement should be handled
      privately and calmly. If what the surveyor is saying doesn't make sense, say,
      "Help me understand." Ask if it is a suggestion or a deviation from compliance.
      Contact the Standards Interpretation Group together. If all else fails,
      electronically submit clarifying evidence of standards compliance.

PMID- 15742793
TI  - Surveyors scrutinize patient rights compliance.
AB  - EDs have several areas where they can fail to comply with patient rights
      standards. Include pain assessment on the delayed nurse report, and reassess for
      pain. A patient rights statement must be given to all patients, whether they are
      admitted. Have admission criteria. They may be included in your scope of service
      document. Ensure your staff members know who obtains consent for emergency
      procedures such as catheterization. Blanket policies can address cases that don't
      have consent. Give patients information on advance directives, and find out if
      the patient is a no code.

PMID- 15742794
TI  - The vision of mental health nursing in Panama.

PMID- 15742795
TI  - Child behavior problems and maternal symptoms of depression: a mediational model.
AB  - PROBLEM: The relationship between maternal depression and child behavior problems
      has been consistently demonstrated, but not the impact of child behavior problems
      on maternal depression. METHODS: Mothers of 3- to 6-year-old children (N=69)
      reported regarding their depression, parenting competence, attachment to the
      child, the child's impact on the family, and behavior problems. FINDINGS: Child
      behavior problems were positively associated with maternal depression, an
      association explained by mediating variables: impact of the child on the family,
      mother's parenting competence, and attachment to the child. CONCLUSIONS: Maternal
      depression should be considered when providing clinical services to children,
      given the potential for exacerbation of symptoms in the face of child behavior
      problems.

PMID- 15742796
TI  - Demons or diamonds: a study to ascertain health professionals' attitudes toward
      children with conduct disorder.
AB  - PROBLEM: In the United Kingdom, 10% of children referred to child psychiatry
      services are diagnosed with a conduct disorder. Of these, 45% may grow up to be
      psychopaths or have personality disorders. Attitudes of professionals to both
      these diagnoses are shown to be negative. METHODS: A Likert-scale questionnaire
      and semistructured interview completed by a purposive sample of doctors, nurses,
      psychologists, and therapists (N=32) in an outpatient child and adolescent mental
      health department. FINDINGS: Positive regard is maintained toward these children
      despite negative expectations for prognosis and treatment. Negative attitudes
      were attributed to lack of resources, medically led services with research-based
      practice agendas, and ethical issues of utilitarianism. CONCLUSIONS: If children
      with conduct disorder continue to be seen as "demons," as untreatable and
      resource intensive, they will continue to be ignored by the agencies who purport
      to help them. Search terms: Attitudes, conduct disorders, personality disorder

PMID- 15742797
TI  - Acute stress disorder symptoms in gunshot-injured youth.
AB  - PROBLEM: The prevalence of acute stress disorder symptoms (ASDS) and other
      psychiatric comorbidities in youth with recent gunshot injuries. METHODS:
      Children (n=20) admitted to an urban hospital ER for gunshot injuries over a 4
      year period were evaluated for ASDS, co-morbid DSM-III-R diagnoses, legal and
      gang involvement, and psychiatric history; medically hospitalized children (n=36)
      similar in age, sex, race, and socioeconomic status served as a control group.
      FINDINGS: Gunshot-injured youth reported a 75% rate of ASDS compared to a 14%
      rate in medically ill youth (OR 18.6; chi2 = p < .0001). Parent ratings of ASDS
      closely corresponded with youth ratings. Youth rated reexperiencing the event as
      the most frequent distressing symptom. Gunshot injury was associated with legal
      problems, gang involvement, marijuana/alcohol dependence, conduct disorder,
      social phobia, and agoraphobia compared to youth with medical illness.
      CONCLUSIONS: Compared to youth with medical illness, gunshot-injured youth were
      18.6 times (p = .0001) more likely to show symptoms of ASDS. Further research,
      developmentally appropriate assessment, prevention, and treatment are needed in
      this area.

PMID- 15742798
TI  - When the system works: rescuing a child from Munchausen's syndrome by proxy.
AB  - This case study presents a consultation-liaison client and family. The author
      illustrates how a coordinated staff effort and the nurse-patient relationship
      resulted in improved treatment.

PMID- 15742799
TI  - New long-acting stimulants in children with ADHD.

PMID- 15742800
TI  - Sala de Psiquiatria de Ninos y Adolescentes (Hall of Psychiatry for Children and
      Adolescents).

PMID- 15742801
TI  - Signal transduction network leading to COX-2 induction: a road map in search of
      cancer chemopreventives.
AB  - Cancer is still a major global health concern even after an everlasting strive in
      conquering this dread disease. Emphasis is now given to chemoprevention to reduce
      the risk of cancer and also to improve the quality of life among cancer afflicted
      individuals. Recent progress in molecular biology of cancer has identified key
      components of the cellular signaling network, whose functional abnormality
      results in undesired alterations in cellular homeostasis, creating a cellular
      microenvironment that favors premalignant and malignant transformation. Multiple
      lines of evidence suggest an elevated expression of cyclooxygenase-2 (COX-2) is
      causally linked to cancer. In response to oxidative/pro-inflammatory stimuli,
      turning on unusual signaling arrays mediated through diverse classes of kinases
      and transcription factors results in aberrant expression of COX-2. Population
      based as well as laboratory studies have explored a broad spectrum of
      chemopreventive agents including selective COX-2 inhibitors and a wide variety of
      anti-inflammatory phytochemicals, which have been shown to target cellular
      signaling molecules as underlying mechanisms of chemoprevention. Thus, unraveling
      signaling pathways regulating aberrant COX-2 expression and targeted blocking of
      one or more components of those signal cascades may be exploited in searching
      chemopreventive agents in the future.

PMID- 15742802
TI  - Synthesis and conformational study of 2-trityloxymethyltetrahydrofurans as key
      intermediates for antiviral nucleosides.
AB  - We wanted to elucidate the reason why the trityloxymethyl substituent in gamma
      trityloxymethyl-gamma-butyrolactone takes a sterically unfavorable specific
      conformation, and so we synthesized 5-trityloxymethyldihydrofuran-3-one, 3
      (trityloxymethyl)-4-butanolide and 2-trityloxymethyl-tetrahydrofuran and we then
      analyzed their conformation by 1H-NMR analysis.

PMID- 15742803
TI  - Antioxidant activity of anthraquinones and flavonoids from flower of Reynoutria
      sachalinensis.
AB  - Bioassay-guided fractionation of methanol extract of Reynoutria sachalinensis
      flower using DPPH assay has led to the isolation of three anthraquinones and
      three flavonoids. Their structures were identified as emodin (1), emodin-8-O-beta
      D-glucopyranoside (2), physcion-8-O-beta-D-glucopyranoside (3), quercetin-3-O
      alpha-L-arabinofuranoside (4), quercetin-3-O-beta-D-galactopyranoside (5), and
      quercetin-3-O-beta-D-glucuronopyranoside (6) by comparing their physicochemical
      and spectral data with those published in literatures. All isolated compounds
      were evaluated for antioxidant activities with free radical 1,1-diphenyl-2
      picrylhydrazyl (DPPH) scavenging, superoxide radical scavenging and Cu2+-mediated
      low density lipoprotein (LDL) oxidation assay. The results demonstrated that
      three flavonoids, 4, 5, and 6 had remarkable antioxidant activities with the IC50
      values of 64.3, 54.7, and 46.2 microM (DPPH scavenging), the IC50 values of 6.0,
      6.7, and 4.4 microM (superoxide radical scavenging) and the IC50 values of 3.8,
      3.2, and 5.4 microM against LDL oxidation, respectively.

PMID- 15742804
TI  - Inhibitory constituents against cyclooxygenases from Aralia cordata Thunb.
AB  - Seven diterpenes, four polyacetylenes, a lipid glycerol, and two sterols were
      isolated from the methylene chloride fraction of the root of Aralia cordata.
      Their chemical structures were determined as (-)-pimara-8(14),15-dien-19-oic acid
      (2), pimaric acid (3), (-)-kaur-16-en-19-oic acid (4), 17-hydroxy-ent-kaur-15-en
      19-oic acid (9), 7alpha-hydroxy-(-)-pimara-8(14),15-dien-19-oic acid (10),
      16alpha,17-dihydroxy-(-)-kauran-19-oic acid (11), 16-hydroxy-17-isovaleroyloxy
      ent-kauran-19-oic acid (12), falcarindiol (5), dehydrofalcarindiol (6),
      dehydrofalcarindiol-8-acetate (7), falcarindiol-8-acetate (8), alpha-mono
      palmitin (13), stigmasterol (1), and daucosterol (14) by the spectral evidences.
      These compounds were tested with COX-1 and COX-2 inhibition assays. This study
      found that compounds 2, 4, 5, 6, 7, 8, and 10 inhibited COX-1 dependent
      conversion of the exogenous arachidonic acid to PGE2 in a dose-dependent manner
      with IC50 values of 134.2 microM, 121.6 microM, 170 microM, 50.4 microM, 11.7
      microM, 99.6 microM, and 69.6 microM, respectively. But, most of these compounds
      weakly inhibited COX-2 dependent PGE2 generation. Among them, only compound 4
      showed relatively significant inhibitory activity (IC50: 127.6 microM).

PMID- 15742805
TI  - A new antipsychotic effective neolignan from Firmiana simplex.
AB  - A new neolignan, named simplidin was isolated from the the n-butanol extract of
      stem of Firmiana simplex, together with six known compounds, scopoletin (1),
      syrigaresinol (2), aquillochin (3), nitidanin (4), tamarixetin 3-rhamnoside (6),
      and quercitrin (7). On the basis of spectral and chemical evidence, simplidin (5)
      was determined to be rel-(7R,8R)-4,5,9,9'-tetrahydroxy-3,3'-dimethoxy-7-O-5',8-O
      4'-neolignan. All the six compounds were also isolated for the first time from
      this plant.

PMID- 15742806
TI  - Antitumor and antiinflammatory constituents from Celtis sinensis.
AB  - Eight compounds were isolated from the methanolic extract of the twigs of Celtis
      sinensis through repeated silica gel and Sephadex LH-20 column chromatography.
      Their chemical structures were elucidated as two triterpenoids, germanicol and
      epifriedelanol, two amide compounds, trans-N-caffeoyltyramine and cis-N
      coumaroyltyramine, two lignan glycoside, pinoresinol glycoside and pinoresinol
      rutinoside, and two steroids by spectroscopic analysis.

PMID- 15742807
TI  - Hepatoprotective constituents of Cudrania tricuspidata.
AB  - Phytochemical investigation of the MeOH extract of the root barks of Cudrania
      tricuspidata Bureau (Moraceae), as guided by hepatoprotective activity in vitro,
      furnished four isoprenylated xanthones, cudratricusxanthone A (1), cudraxanthone
      L (2), cudratricusxanthone E (3), and macluraxanthone B (4). All of these
      compounds showed the significant hepatoprotective effect on tacrine-induced
      cytotoxicity in human liver-derived Hep G2 cells. Compounds 1, 2, and 4 also
      exhibited the significant hepatoprotective effect on nitrofurantoin-induced
      cytotoxicity in human liver-derived Hep G2 cells.

PMID- 15742808
TI  - Immunobiological [correction of Immunobioloical] activity of a new benzyl
      benzoate from the aerial parts of Solidago virga-aurea var. gigantea.
AB  - The chromatographic separation of the hexane soluble fraction of the methanol
      extract of the aerial parts of Solidago virga-aurea var. gigantea M(IQ*)
      (Compositae) led to the isolation of a new benzylbenzoate (1) together with four
      known benzylbenzoates (2-5). Their structures were determined as 2-methoxybenzyl
      2-hydroxybenzoate (1), benzyl-2-hydroxy-6-methoxybenzoate (2), 2-methoxybenzyl
      2,6-dimethoxybenzoate (3), 2-methoxybenzyl-2-methoxy-6-hydroxybenzoate (4), and
      benzyl-2,6-dimethoxybenzoate (5). Their structures were established by
      spectroscopic methods. Biological effects of compounds, 1 and 2, were
      investigated in vitro using mouse peritoneal macrophages. The benzylbenzoates (1
      and 2) could serve as immunotherapeutic agents by stimulating macrophage
      functions, with potential use in the treatment of infectious diseases.

PMID- 15742809
TI  - Manassantin A and B isolated from Saururus chinensis inhibit TNF-alpha-induced
      cell adhesion molecule expression of human umbilical vein endothelial cells.
AB  - Leukocyte adhesion to the vascular endothelium is a critical initiating step in
      inflammation and atherosclerosis. We have herein studied the effect of
      manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic
      cells and human umbilical vein endothelial cells (HUVEC) and expression of
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2
      followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC
      decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL,
      respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up
      regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1
      and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1
      and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness
      for the prevention of atherosclerosis relevant to endothelial activation.

PMID- 15742810
TI  - BMS-191095, a cardioselective mitochondrial K(ATP) opener, inhibits human
      platelet aggregation by opening mitochondrial K(ATP) channels.
AB  - We evaluated the antiplatelet effects of two classes of ATP-sensitive potassium
      channel openers (K(ATP) openers) on washed human platelets, and the study's
      emphasis was on the role of mitochondrial K(ATP) in platelet aggregation.
      Collagen-induced platelet aggregation was inhibited in a dose dependent manner by
      lemakalim and SKP-450, which are potent cardio-nonselective K(ATP) openers, and
      also by cardioselective BMS-180448 and BMS-191095 (IC50: 1,130, >1,500, 305.3 and
      63.9 microM, respectively), but a significantly greater potency was noted for the
      cardioselective K(ATP) openers. The latter two K(ATP) openers also inhibited
      platelet aggregation induced by thrombin, another important blood-borne platelet
      activator, with similar rank order of potency (IC50: 498.0 and 104.8 microM for
      BMS-180448 and BMS-191095, respectively). The inhibitory effects of BMS-191095 on
      collagen-induced platelet aggregation were significantly blocked by a 30-min
      pretreatment of platelets with glyburide (1 microM) or sodium 5-hydroxydecanoate
      (5-HD, 100 microM), a nonselective and selective mitochondrial K(ATP) antagonist,
      respectively, at similar magnitudes; this indicates the role of mitochondrial
      K(ATP) in the antiplatelet activity of BMS-191095. However, glyburide and 5-HD
      had no effect when they were added to the platelet cuvette immediately prior to
      the addition of BMS-191095. These findings indicate that cardioselective
      mitochondrial K(ATP) openers like BMS-191095 are able to exert cardioprotective
      effects in cardiac ischemia/reperfusion injury via dual mechanisms directed at
      the inhibition of platelet aggregation and the protection of cardiomyocytes, and
      both these mechanisms are mediated by mitochondrial K(ATP).

PMID- 15742811
TI  - Pseudolaric acid B induces apoptosis through p53 and Bax/Bcl-2 pathways in human
      melanoma A375-S2 cells.
AB  - Pseudolaric acid B is a major compound found in the bark of Pseudolarix kaempferi
      Gordon. In our study, pseudolaric acid B inhibited growth of human melanoma
      cells, A375-S2 in a time- and dose-dependent manner. A375-S2 cells treated with
      pseudolaric acid B showed typical characteristics of apoptosis including
      morphologic changes, DNA fragmentation, sub-diploid peak in flow cytometry,
      cleavage of poly-ADP ribose polymerase (PARP) and degradation of inhibitor of
      caspase-activated DNase (ICAD). P53 protein expression was upregulated while
      cells were arrested at the G2/M phase of the cell cycle. There was a decrease in
      the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins, whereas pro-apoptotic
      Bax was increased. The two classical caspase substrates, PARP and ICAD, were both
      decreased in a time-dependent manner, indicating the activation of downstream
      caspases.

PMID- 15742812
TI  - A phospholipase C-dependent intracellular Ca2+ release pathway mediates the
      capsaicin-induced apoptosis in HepG2 human hepatoma cells.
AB  - The effect of capsaicin on apoptotic cell death was investigated in HepG2 human
      hepatoma cells. Capsaicin induced apoptosis in time- and dose-dependent manners.
      Capsaicin induced a rapid and sustained increase in intracellular Ca2+
      concentration, and BAPTA, an intracellular Ca2+ chelator, significantly inhibited
      capsaicin-induced apoptosis. The capsaicin-induced increase in the intracellular
      Ca2+ and apoptosis were not significantly affected by the extracellular Ca2+
      chelation with EGTA, whereas blockers of intracellular Ca2+ release (dantrolene)
      and phospholipase C inhibitors, U-73122 and manoalide, profoundly reduced the
      capsaicin effects. Interestingly, treatment with the vanilloid receptor
      antagonist, capsazepine, did not inhibit either the increased capsaicin-induced
      Ca2+ or apoptosis. Collectively, these results suggest that the capsaicin-induced
      apoptosis in the HepG2 cells may result from the activation of a PLC-dependent
      intracellular Ca2+ release pathway, and it is further suggested that capsaicin
      may be valuable for the therapeutic intervention of human hepatomas.

PMID- 15742813
TI  - Protective effects of chalcone derivatives for acute liver injury in mice.
AB  - The hepatoprotective effects of chalcone derivatives were evaluated in D
      galactosamine/lipopolysaccharide (D-GalN/LPS)-induced fulminant hepatic failure
      in mouse. Thirteen chalcone derivatives were synthesized for study and their
      hepatoprotective effects were evaluated by assessing aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) levels in serum. Chalcone preparations
      were injected into mice at 12 h and 1 h before intraperitoneal injection of D
      GalN/LPS. After abdominal administration, changes in AST and ALT between the
      control and treated groups were observed. Ten of the synthesized chalcone
      derivatives exhibited inhibitory effects on D-GalN/LPS-induced levels of AST and
      ALT in mice. Compounds 2, 3, 8, 9, and 12 markedly reduced serum AST and ALT at 8
      h, inhibited hepatocyte necrosis and showed significant hepatoprotective
      activities. The activity of compound 3 was compared with the bifendate (DDB)
      through oral administration. Compound 3 showed much higher inhibitory effects
      than bifendate for decreasing AST and ALT activity. The results indicate that
      compound 3 has strong hepatoprotective activity through suppression of tumor
      necrosis factor-alpha (TNF-alpha) preduction, reduction of the histological
      change in the liver, and attenuated of hepatocyte apoptosis confirmed by DNA
      fragmentation assay.

PMID- 15742814
TI  - Potentiation of ceramide-induced apoptosis by p27kip1 overexpression.
AB  - The cyclin-dependent kinase inhibitor p27kip1 (p27) has been implicated in the
      regulation of cell cycle and apoptosis. Recently, we have demonstrated that
      ceramide induces apoptotic cell death associated with increase in the level of
      p27 in HL-60 cells. In the present study, we showed that overexpression of p27
      increases ceramide-induced apoptotic cell death in HL-60 cells. Furthermore,
      overexpression of p27 accelerated DNA fragmentation, PARP cleavage and cytochrome
      c release induced by ceramide. In addition, ceramide induced Bax expression
      independent of p27. These findings indicate that enhanced effect on apoptosis by
      p27 is associated with mitochondrial signaling which involves cytochrome c
      release.

PMID- 15742815
TI  - Intracellular trafficking of transferrin-conjugated liposome/DNA complexes by
      confocal microscopy.
AB  - Intracellular trafficking of transferrin-conjugated dimethyldioctadecyl-ammonium
      bromide liposome (T1-liposome)/DNA complexes in HeLa cells was studied using the
      double-labeled fluorescence technique and confocal microscopy. The size of the T1
      liposome/DNA complex was about 367 nm in diameter and the zeta-potential of it at
      a 5:1 (w/w) ratio was almost neutral. The intracellular pathway of the T1
      liposome/DNA complex, noted as green (FITC), red (rhodamine) or yellow (FITC +
      rhodamine) fluorescence, was elucidated from the plasma membrane to the endosome
      (or lysosome), and finally to the nucleus. The results of this study indicate
      that plasmid DNA enters into the nucleus not only as a free form but as an
      associated form complexed with T1-liposome. More interestingly, the T1-liposome
      undergoes a nuclear location in the form of ordered structures. This could be a
      very useful piece of information in designing a safe and advanced gene delivery
      system.

PMID- 15742816
TI  - Effects of mancozeb on the activities of murine peritoneal macrophages in vitro
      and ex vivo.
AB  - Mancozeb (MCZ) is known to have detrimental effects on the reproductive system,
      but the toxicity of MCZ on immune responses has not been systematically
      investigated. We investigated the effects of MCZ exposure on the activities of
      murine peritoneal macrophages through evaluation of MCZ-induced alteration of
      nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-alpha)
      synthesis. Macrophages were examined ex vivo from mice orally treated with
      various doses of MCZ for 5 consecutive days per week for 4 weeks (subacute
      exposure, 250, 1000, 1500 mg/kg/day) followed by culture for 2 (TNF-alpha) or 3
      days (NO) in the presence of LPS plus IFN-gamma. Macrophages from naive mice were
      also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2
      microg/mIL in the presence of LPS plus IFN-gamma for 2 (TNF-alpha) or 3 days (NO)
      in vitro. NO production was decreased with the in vitro exposure to all
      concentrations of MCZ. However, the amount of NO production by peritoneal
      macrophages from MCZ-subacutely exposed mice was increased in comparision with
      that of control group. In vitro, MCZ suppressed TNF-alpha secretion with
      significant reduction at 2 microg/mL MCZ. Conversely, TNF-alpha release was
      enhanced ex vivo. This study provides the substantial evidence on MCZ-induced
      alternation in macrophage activity. In order to clearly understand the
      contrasting effect of MCZ on peritoneal macrophage activity, it is necessary to
      further investigate the influence of major metabolite of MCZ (ETU) exposure on
      the NO production and TNF-alpha synthesis.

PMID- 15742817
TI  - Bone loss preventing effect of Sophorae Fructus on ovariectomized rats.
AB  - The preventive effects of Sophorae Fructus extracts (I: hot water extract and II:
      combination product using I) on bone loss in ovariectomized (OVX) rats were
      investigated. Sophorae Fructus extracts were orally administrated to OVX rats for
      9 weeks. Ovariectomy caused the increase of body weight and deoxypyridinoline
      (Dpd: bone resorption marker) and decrease of calcium (Ca: bone formation marker)
      level in serum. Dpd level were significantly decreased and Ca levels were
      elevated at 9 weeks in Sophorae Fructus extracts administered groups after
      ovariectomy at a dose of 0.556 g/kg/day compared with control group. In
      administered groups, trabecular bone area (TBA) in the tibia and lumbar were also
      increased compared with control group in histomorphological analysis. The
      preventive or treatment effects of Sophorae Fructus extracts on bone loss in OVX
      rats appears to be due to suppression of bone turnover.

PMID- 15742818
TI  - Antihistamine effects of triprolidine from the transdermal administration of the
      TPX matrix in rats.
AB  - The antihistamine effects of the triprolidine were studied in rats to determine
      the feasibility of their enhanced transdermal delivery from the poly (4-methyl-1
      pentene) (TPX) matrix system containing penetration enhancer and plasticizer. The
      antihistamine effects were determined by the Evans blue dye procedure by
      comparing the changes in vascular permeability increase following the transdermal
      administration. The vascular permeability increase was significantly reduced by
      transdermal administration of the triprolidine-TPX system containing triethyl
      citrate (TEC) and polyoxyethylene-2-oleyl ether (POE). Both the plasticizer and
      penetration enhancer played an important role in the skin permeation of
      triprolidine and increased the antihistamine effects. These results showed that
      the triprolidine-TPX matrix system containing plasticizer and penetration
      enhancer could be a transdermal delivery system providing the increased
      antihistamine effects.

PMID- 15742819
TI  - Effect of 2-methylaminoethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2
      carboxylic acid-2'-carboxylate monohydrochloride (DDB-S) on indocyanine green
      (ICG) clearance in rats.
AB  - The clearance of ICG, a known hepatic blood flow marker was investigated in rats
      in order to examine whether DDB-S influences hepatic blood flow. The effect of
      DDB-S on the protein binding and blood-to-plasma partition of ICG was measured.
      The steady-state plasma concentration of ICG was monitored before and after co
      administration of various concentration of DDB-S, and ICG clearance was estimated
      from the steady-state concentration and the infusion rate of ICG. There was no
      significant difference in protein binding and blood-to-plasma partition of ICG
      with and without addition of DDB-S (10, 20, and 40 microg/mL). When ICG was
      infused into DDB-S pretreated rats, the steady-state concentrations of ICG
      decreased and the calculated ICG clearance increased. However, no dose-dependency
      of ICG Css on DDB-S Css was observed. Since DDB-S did not affect the protein
      binding and blood-to-plasma partition of ICG, the increased clearance of ICG with
      co-administration of DDB-S seems to be due to the increased hepatic blood flow by
      DDB-S.

PMID- 15742820
TI  - Surfactant effects upon dissolution patterns of carbamazepine immediate release
      tablet.
AB  - The objective of this study was to investigate the effects of sodium lauryl
      sulfate upon the saturation solubility of carbamazepine, its dissolution
      kinetics, and T50% defined as the time required for dissolving 50% of
      carbamazepine. Water, 0.1 N-HCl, and phosphate buffers at pH 4.0 and 6.8
      containing 0.1, 0.5, 1, and 2% sodium lauryl sulfate were used as dissolution
      media. The dissolution study was conducted by using the USP dissolution apparatus
      II with an agitation rate of 75 rpm. Samples of the dissolution media were taken
      in 7, 15, 30, 45, 60, 75, and 90 min, and the amounts of carbamazepine were
      determined spectrophotometrically at 285 nm. All dissolution data were fitted
      well into a four-parameter exponential equation: Q = a(1 - e(-b x t)) + c(1 - e(
      d x t)). In this equation Q represented % carbamazepine dissolved at a time t,
      and a, b, c, and d were constants. This equation led to the calculation of
      dissolution rates at various time points and T50%. It was found that the
      dissolution rate of carbamazepine was directly proportional to the aqueous
      concentration of sodium lauryl sulfate. In addition, under our experimental
      conditions T50% values ranged from 37.8 to 4.9 min. It was interesting to note
      that T50% declined rapidly as the surfactant concentration increased from 0.1 to
      0.5%, whereas it declined more slowly at concentrations greater than 1%. These
      results clearly demonstrated that the dissolution rate of carbamazepine and
      duration of its dissolution test could be tailored by optimizing the amount of
      sodium lauryl sulfate in a dissolution medium.

PMID- 15742821
TI  - Intracranial pressure dynamics assessed by noninvasive ultrasound during 30 days
      of bed rest.
AB  - INTRODUCTION: Intracranial pressure (ICP) may be an important contributor to
      symptoms of space adaptation syndrome during the initial days of microgravity
      exposure. The temporary nature of these symptoms suggests that some physiologic
      adaptation or compensation occurs. Fluid shifts similar to those in microgravity
      can be simulated on Earth using head-down tilt (HDT) bed rest. This study was
      performed to calibrate a new noninvasive ICP instrument and to investigate ICP
      adaptation during 30 d of HDT bed rest. METHODS: A noninvasive ultrasound
      technique that measures small skull expansions with fluctuations in ICP was used
      to measure cranial oscillations before and near the end of 30-d HDT bed rest in
      eight healthy, male volunteers. Pulse phase-locked loop (PPLL) output voltage and
      arterial BP were continuously monitored and correlated. RESULTS: The amplitude of
      intracranial distance pulsation decreased during 30-d bed rest. Prior to bed
      rest, the PPLL amplitude was 25 +/- 9 mV and this amplitude was reduced by 60% to
      9 +/- 4 mV (a value consistent with that of upright posture) at the end of HDT
      bed rest (p = 0.01). DISCUSSION: PPLL measurements of skull pulsations are
      acutely posture dependent, being significantly higher in supine and HDT as
      compared with upright posture. A cephalad fluid shift is probably the responsible
      mechanism. Our results indicate that there are adaptations to intracranial
      pooling of blood and tissue fluid during bed rest that reduce skull pulsation
      amplitudes to values similar to those obtained in normal upright posture.
      Detailed studies of the time course of cranial vessel and bone adaptations may
      provide insights into the potential adaptative mechanisms.

PMID- 15742822
TI  - Cerebral hypoperfusion precedes nausea during centrifugation.
AB  - INTRODUCTION: Nausea and motion sickness are important operational concerns for
      aviators and astronauts. Understanding the underlying mechanisms associated with
      motion sickness may lead to new treatments. The goal of this work was to
      determine if changes in cerebral blood flow precede the development of nausea in
      subjects susceptible to motion sickness. METHODS: Cerebral flow velocity in the
      middle cerebral artery (transcranial Doppler), BP, and end-tidal CO2 were
      measured while subjects were rotated on a centrifuge (250 degrees x s(-1)).
      Following 5 min of rotation, subjects were translated 51.5 cm off-center,
      creating a +1 Gx centripetal acceleration in the nasal-occipital plane. RESULTS:
      There were 10 subjects who completed the protocol without symptoms while 5
      developed nausea (4 while off-center and 1 while rotating on-center). Prior to
      nausea, subjects had significant increases in BP (+13 +/- 3 mmHg, p < 0.05) and
      cerebrovascular resistance (+46 +/- 17%, p < 0.05) and decreases in cerebral flow
      velocity both in the second (-13 +/- 4%) and last minute (-22 +/- 5%) before
      symptoms (p < 0.05). In comparison, subjects resistant to motion sickness
      demonstrated no change in BP or cerebrovascular resistance in the last minute of
      off-center rotation and only a 7 +/- 2% decrease in cerebral flow velocity. All
      subjects had significant hypocapnia (-3.8 +/- 0.4 mmHg, p < 0.05); however, this
      hypocapnia could not fully explain the cerebral hypoperfusion associated with the
      development of nausea. CONCLUSIONS: These data indicate that reductions in
      cerebral blood flow precede the development of nausea. Further work is necessary
      to determine what role cerebral hypoperfusion plays in motion sickness and
      whether cerebral hypoperfusion can be used to predict the development of nausea
      in susceptible individuals.

PMID- 15742823
TI  - Isoproterenol accelerates decompression sickness and death after saturation dives
      in swine.
AB  - BACKGROUND: Disabled submarine (DISSUB) survivors are expected to achieve inert
      gas tissue saturation that would likely cause severe decompression sickness
      (DCS). Rescue procedures in a DISSUB scenario cannot accommodate a staged
      decompression and the availability of recompression treatment chambers is
      limited. Alternatives to the standard recompression procedures for treating DCS
      are needed. Experimentally, isoproterenol has successfully addressed many
      underlying physiological concerns expected to result in cardiopulmonary DCS in
      this group. HYPOTHESIS: We hypothesized that isoproterenol would reduce the
      incidence of cardiopulmonary DCS in a saturation dropout model. METHODS:
      Yorkshire swine (21.8 +/- 1.68 kg) were fitted with an external jugular catheter
      and compressed to 4.33 ATA in a dry chamber for 22 h. They were infused with
      isoproterenol (0.002 mg x kg(-1)) while still at depth and returned to the
      surface without decompression stops. They received additional infusions every 10
      min throughout a 2-h observation period. Signs of DCS were recorded to the
      nearest minute. RESULTS: Isoproterenol administration resulted in a significant
      increase in the incidence of severe cardiopulmonary DCS (13/34 control vs. 12/18
      isoproterenol) and death from DCS (10/34 control vs. 11/18 isoproterenol). There
      was no difference in the incidence of severe neurological DCS. CONCLUSIONS:
      Administering isoproterenol as an intervention/treatment for DCS significantly
      increases the risk of cardiopulmonary DCS and death following saturation dropout
      in 20-kg swine. As an adjunctive therapy or alternative to staged decompression,
      isoproterenol in the dose regimen delivered here is not expected to improve
      outcome in a DISSUB mass casualty scenario.

PMID- 15742824
TI  - Localization of virtual sound at 4 Gz.
AB  - INTRODUCTION: Acceleration directed along the body's z-axis (Gz) leads to
      misperception of the elevation of visual objects (the "elevator illusion"), most
      probably as a result of errors in the transformation from eye-centered to head
      centered coordinates. We have investigated whether the location of sound sources
      is misperceived under increased Gz. METHOD: Visually guided localization
      responses were made, using a remotely controlled laser pointer, to virtual
      auditory targets under conditions of 1 and 4 Gz induced in a human centrifuge. As
      these responses would be expected to be affected by the elevator illusion, we
      also measured the effect of Gz on the accuracy with which subjects could point to
      the horizon. RESULTS: Horizon judgments were lower at 4 Gz than at 1 Gz, so sound
      localization responses at 4 Gz were corrected for this error in the
      transformation from eye-centered to head-centered coordinates. We found that the
      accuracy and bias of sound localization are not significantly affected by
      increased Gz. CONCLUSION: The auditory modality is likely to provide a reliable
      means of conveying spatial information to operators in dynamic environments in
      which Gz can vary.

PMID- 15742825
TI  - Caffeine effects on recovery sleep following 27 h total sleep deprivation.
AB  - INTRODUCTION: Caffeine is widely used to reverse alertness and performance
      decrements. However, caffeine's effects on subsequent recovery sleep and post
      recovery performance are not well documented and, therefore, were evaluated.
      METHODS: Six habitually low (LC: < or = 100 mg x d(-1)) and three habitually high
      (HC: > or = 400 mg x d(-1)) caffeine users completed a randomized crossover
      design. After 20 h of wakefulness, repeated doses of caffeine gum [0 (placebo)
      mg, 100 (low dose) mg, or 300 (high dose) mg] were administered at 03:00, 05:00,
      and 07:00. At 10:00 (27 h sleep deprivation) subjects slept for 8 h, followed by
      Psychomotor Vigilance Task (PVT) administration at 33 and 65 min post-awakening.
      RESULTS: Low dose caffeine increased stage 1 minutes only. However, high dose
      caffeine impaired sleep maintenance (reduced total sleep time/increased wake) and
      reduced sleep depth (increased stage 1 minutes/percentage and slow-wave sleep
      (SWS) latency, and reduced SWS minutes during the first third of the sleep
      period). With high dose caffeine, LC users had less SWS percentage as compared
      with HC users. The HC users had reduced stage 2 percentage with high dose
      caffeine as compared with placebo and low dose caffeine. Caffeine dose and
      habitual caffeine use did not influence post-recovery sleep PVT performance.
      DISCUSSION: Caffeine exerts mild deleterious dose-response effects on recovery
      sleep following total sleep deprivation, primarily early in the sleep period,
      with potential recovery from these effects after sufficient sleep as suggested by
      lack of post-recovery sleep performance deficits. Habitual caffeine use appears
      to minimally reduce caffeine effects.

PMID- 15742826
TI  - N-terminal pro brain natriuretic peptide increases after 1-h scuba dives at 10 m
      depth.
AB  - OBJECTIVES: The N-terminal pro brain natriuretic peptide (N-BNP) is a promising
      cardiac natriuretic peptide used as a clinical hormonal marker in cardiac
      dysfunction. The main stimulus for N-BNP synthesis and secretion is cardiac wall
      stress, which is recognized as a common denominator of many cardiac diseases.
      Diving is associated with environmental factors leading to variations in thoracic
      blood volume and hemodynamic changes. The purpose of the present study was to
      examine the changes in the concentration of N-BNP in healthy men during and after
      scuba diving. METHOD: There were 10 healthy military divers (mean age 33 yr) who
      performed a dive in the sea for 1 h at 10 m depth. Venous blood samples were
      taken at timed intervals to allow evaluation of plasma levels of N-BNP at
      different steps, namely at To (before immersion), at T30 min (during the dive,
      after a short surfacing), at T60 min (right after surfacing), at T300 min (post
      dive), and finally at T24 h. Peptide blood concentrations were determined by
      electrochemoluminiscence immunoassay. Data were analyzed using parametric
      statistics. RESULTS: When compared with To, the results show a significant
      increase of N-BNP levels (in % of baseline levels) at T60(128 +/- 5%, p < 0.043)
      and at T300 (149 +/- 8%, p < 0.001). CONCLUSION: This preliminary study reveals
      that N-BNP rises with scuba diving. Our findings suggest that diving involves a
      mechanical strain on the heart with a persistent endocrine myocardial activity
      post-dive.

PMID- 15742827
TI  - Fos expression in the suprachiasmatic nucleus in rats following high altitude
      exposure.
AB  - INTRODUCTION: Disturbances of circadian rhythms occur at high altitude. We
      examined the suprachiasmatic nucleus (SCN), considered to be the biological clock
      in mammals that regulates circadian rhythmicity, in adult rats following an
      exposure to simulated high altitude. METHODS: Male adult Wistar rats weighing 250
      g were exposed to an altitude of 8000 m in an altitude chamber, following which
      they were sacrificed at various time intervals ranging from 45 min to 3 d. Normal
      rats of similar weight kept outside the chamber were used as controls. Sections
      of hypothalamus containing the suprachiasmatic nucleus were processed
      immunohistochemically for expression of Fos, neuronal nitric oxide synthase
      (nNOS), and endothelial nitric oxide synthase (eNOS). RESULTS: At 45 min, 4 h,
      and 24 h following the altitude exposure, a large number of Fos-positive neurons
      were detected as compared with the control rats in which occasional Fos-positive
      neurons were observed. Increased expression of nNOS and eNOS was also observed at
      45 min and 4 h following the altitude exposure. CONCLUSIONS: It is suggested that
      the neuronal activation indicated by upregulated expression of Fos and nitric
      oxide (NO) generated by nNOS may be involved in the disturbed circadian rhythms
      of the cardiovascular system (e.g., heart rate and BP), hormone secretion, and
      sleep-wake cycle which occur frequently during sojourns to high altitude.
      Increased eNOS expression also indicates excess production of NO, which may be
      involved in vasodialation and increased blood flow to the SCN following the
      exposure and may also be involved in modulating the circadian rhythms at high
      altitude.

PMID- 15742828
TI  - Psychostimulants and G tolerance in rhesus monkeys: effects of oral modafinil and
      injected caffeine.
AB  - INTRODUCTION: Caffeine and modafinil are psychostimulants that may be taken by
      fighter aircraft pilots to reduce fatigue. Fighter pilots are subjected to high
      positive G loads that reduce cerebral blood flow and consequently may induce G
      LOC. The aim of the experiment was to determine whether these drugs may reduce
      tolerance to G stress. METHODS: Seven adult male rhesus monkeys participated in
      the experiment. Five were equipped with ECoG and ECG wires and underwent two G
      tests (A and B). Each experiment consisted of five centrifuge runs. Before the
      runs, the monkeys received no drug (control) or were given either 7.5 mg x kg(-1)
      caffeine IM or 64 mg x kg(-1) modafinil PO or the corresponding vehicles. The
      runs were performed up to +13 Gz with an onset rate of 0.1 G x s(-1) (test A) or
      3 G x s(-1) (test B). The run was ended when the electrical activity of one ECoG
      channel had disappeared (i.e., G-LOC). RESULTS: In experiment A, drug
      administration had no significant effect. In experiment B, the injection of the
      caffeine-free solvent caused a delay in G-LOC compared with the control condition
      (no administration). Caffeine solvent also induced an increase in plasma
      osmolality. DISCUSSION: Modafinil administration has no significant effect on the
      G tolerance of rhesus monkeys. Regarding caffeine, the drug seems to have caused
      the reverse effect compared with the solvent. CONCLUSIONS: Caffeine and modafinil
      administration had no significant effect on the G-tolerance of rhesus monkeys
      when compared with controls. This result needs to be confirmed in humans.

PMID- 15742829
TI  - Aviation-relevent epidemiology of color vision deficiency.
AB  - INTRODUCTION: The Colour Vision Study Group of Transport Canada undertook a
      prevalence review to ascertain the degree and type of color vision deficiency
      (CVD) common in different populations. This was performed as a first step toward
      establishing whether a bone fide occupational requirement for color vision in
      aviation can be determined. LITERATURE SEARCH: Peer-reviewed articles with large
      populations and appropriate methodology for measuring CVD were assessed. Those
      pertaining to congenital CVD were cross-sectional prevalence studies with greater
      than 100 subjects assessed with a combination of pseudoisochromatic plates (PIPs)
      and Farnsworth D15 and/or an anomaloscope. Of 162 papers reviewed, 36 met these
      criteria for inclusion in the congenital CVD section. Acquired CVD papers were
      included based on the quality of color vision tests employed. CONGENITAL CVD:
      Data on congenital and acquired CVD are presented separately in parts 1 and 2.
      Part 1 demonstrates that although the prevalence numbers for North American and
      European populations are consistent with those reported in reference texts,
      congenital CVD is actually less prevalent in Asian, African, and Native
      populations. Therefore, the reported overall 8% prevalence of CVD in men applies
      only to Euro-Caucasians and is significantly lower in other racial groups.
      Possible evolutionary implications of dichromatism in humans are explored.
      ACQUIRED CVD: In this section the current understanding of acquired color vision
      deficiency, with an estimated prevalence ranging from 5 to 15% (51,95), is
      reviewed. Acquired CVD is frequently associated with significant impairment of
      visual acuity and/or visual field. However, many ocular diseases and drugs do
      primarily affect color vision, independent of other visual function, and one must
      remain vigilant to their presence. CONCLUSION: Congenital CVD is present in a
      consequential percentage of men, but considerable variability exists in different
      populations (2-8%). Acquired CVD may elude detection, but if severe is also
      associated with loss of visual acuity and/or visual field. Senescence remains the
      most common and increasingly prevalent cause for acquired CVD.

PMID- 15742830
TI  - Cognitive paralysis in an emergency: the role of the supervisory attentional
      system.
AB  - Many witnesses attest that victims of a disaster often perish because they
      'freeze' in the face of danger. It has been proposed that this cognitive
      paralysis occurs due to temporal and cognitive constraints on survival response
      times while leaving open the question of which cognitive component is implicated
      in this behavior. This paper proposes, firstly, that the temporal constraints
      which occur during an emergency inhibit the functioning of the supervisory
      attentional system (SAS), which leads to the victim showing: (1) an appropriate
      response, if trained; (2) stereotypical or otherwise irrational behavior, if
      untrained; or (3) cognitive paralysis. Secondly, that the main role of the SAS is
      to operate as a temporal buffer, enabling a survival response to be prepared
      prior to facing a life-threatening event and not as a real-time immediate
      responder. It is argued that the initial cognitive paralysis differs at the
      cognitive and neurological levels from the more prolonged hypoactive behavior
      commonly seen in victims rescued from disasters and which is considered to be a
      form of disassociative reaction.

PMID- 15742831
TI  - Isolated dextrocardia in a commercial pilot candidate.
AB  - Positional anomalies of the heart are rare and are seldom found during routine
      physical examinations. We describe the case of a 25-yr-old Swiss airline pilot
      candidate whose aeromedical examination was normal except that an unusual ECG
      raised suspicion, leading to a diagnosis of dextrocardia with a normal
      arrangement of atria and abdominal viscera. This diagnosis in a pilot candidate
      should raise concern because a high percentage of such individuals have
      congenital heart defects. Further tests were conducted to rule out associated
      cardiac malformations, conduction anomalies, or rhythm disturbances. Testing also
      excluded other associated diseases such as primary ciliary dyskinesia and
      Kartagener's syndrome. Dextrocardia is not listed as a disqualifying condition in
      the applicable aeromedical regulations (Joint Aviation Authorities Medical
      Manual, Joint Aviation Requirements-Flight Crew Licensing guidelines). Therefore,
      after demonstrating that there were no physical, hemodynamic, or
      electrophysiological abnormalities, the candidate was allowed to enroll in
      civilian pilot training without restrictions.

PMID- 15742832
TI  - Laparoscopic inguinal hernioplasty in aviators.
AB  - Repair of inguinal hernias may be performed using either open surgery or
      laparoscopic techniques. Following surgery, a 6-wk waiting period is generally
      recommended before a pilot returns to active duty, including flight in high
      performance aircraft. A shorter waiting period would be operationally useful and
      may be possible following either a trans-abdominal preperitoneal (TAPP)
      laparoscopic technique or a totally extra-peritoneal (TEP) approach. In this
      manuscript we present the cases of four aviators who underwent inguinal hernia
      repair via the TEP approach and were returned to the cockpit 21 d later with no
      evident complications. Although this sample is small, it emphasizes the potential
      benefit of the TEP approach in aviators.

PMID- 15742833
TI  - Sinus vein thrombosis following exposure to simulated high altitude.
AB  - A relation exists between high altitude exposure and a hypercoagulable state, the
      nature of which is not entirely clear. This has been mostly reported in mountain
      climbers. We report a 19-yr-old female, working as a high-altitude chamber
      instructor, who presented with severe frontal headaches which persisted for a
      month following routine high altitude chamber training. The patient was in
      generally good health and was using oral contraceptives for 3 yr prior to the
      event. Due to the unremitting nature of the symptoms, the patient was admitted to
      a neurology department, and computerized tomography (CT) and magnetic resonance
      imaging (MRI) were performed. Sagittal and transverse sinus vein thrombosis were
      diagnosed and anticoagulant therapy was initiated (low molecular weight heparin
      followed by warfarin). Following treatment, a slow symptomatic improvement was
      observed, and the patient was discharged. On discharge, it was recommended she
      continue oral anticoagulant therapy (warfarin). A complete coagulation screening
      panel was performed, which was negative. Although the relation between high
      altitude exposure and a hypercoagulable state is well known, this is the first
      time a case of sinus vein thrombosis has been reported after high altitude
      chamber training. Careful history and closely monitored medical follow-up should
      be performed on all designated staff exposed to simulated altitude. Even though
      there is no conclusive evidence regarding it, we suggest, as a matter of caution,
      that women using oral contraceptives should consider their risks before deciding
      to undertake exposure to simulated altitude in chambers. Literature review and
      detailed recommendations for prevention are provided.

PMID- 15742834
TI  - Traumatic iridodialysis in a student naval aviator applicant.
AB  - Iridodialysis is a relatively uncommon but important sequela of blunt trauma to
      the eye. It classically presents as a form of polycoria or extra pupil observed
      during a comprehensive eye examination. This defect results from compression of
      the anterior-posterior aspect of the globe itself, which stretches the anterior
      ring segments and leads to the separation of the iris root from the ciliary body.
      Degraded visual acuity and visual confusion from glare as well as several late
      stage pathologic sequelae may result from the injury. Establishing the diagnosis
      in aviators is important since any visual disturbance may incapacitate the pilot,
      resulting in a mishap or interference with completion of the mission. We present
      a case of a student naval aviator applicant who presented to the Naval Aerospace
      Medical Institute on two separate occasions for medical evaluation of duties
      involving flying after suffering blunt trauma/iridodialysis to his right eye.

PMID- 15742835
TI  - You're the flight surgeon. Closed head injury.

PMID- 15742836
TI  - Critical care medicine in space.

PMID- 15742837
TI  - Reader disputes WMTS data.

PMID- 15742838
TI  - Telemedicine behind bars: a cost-effective and secure trend.

PMID- 15742839
TI  - Getting a new facility up and running.

PMID- 15742840
TI  - How to land the job that's right for you.

PMID- 15742841
TI  - Implementation of a homegrown computerized management system.

PMID- 15742842
TI  - How to troubleshoot...anything! Part I: Exterior troubleshooting.

PMID- 15742843
TI  - JCAHO officials provide guidance on new patient safety goals.

PMID- 15742844
TI  - "What are we preventing?" Performing PM on hospital beds.

PMID- 15742845
TI  - Gas-flow analyzers.

PMID- 15742846
TI  - Viruses, worms, and Trojans.

PMID- 15742847
TI  - Equipment inspectors focus on preventive maintenance.

PMID- 15742848
TI  - Are you listening? Tips on improving your communication skills.

PMID- 15742849
TI  - Medical equipment problem solving: spotlight on centrifuges.

PMID- 15742850
TI  - How to kick-start your CAPA process.

PMID- 15742851
TI  - Engineering for patient safety: the clinically driven approach.

PMID- 15742852
TI  - Gait analysis.
AB  - Gait analysis, or the study of locomotion, has changed dramatically over the last
      few decades. Advances in computer technology and data analysis techniques have
      contributed greatly to the progress of this field. Gait analysis has become a
      valuable tool in the clinical setting. The ability to objectively quantify motion
      is essential to our understanding of normal and abnormal movement patterns and
      the evaluation of treatment effectiveness. This paper will discuss the various
      experimental and analytical techniques currently used for performing clinical
      gait analyses at the University of New Brunswick, Fredericton, New Brunswick,
      Canada.

PMID- 15742853
TI  - Development of high-sensitivity near-infrared fluorescence imaging device for
      early cancer detection.
AB  - We have developed a high-sensitivity near-infrared (NIR) optical imaging system
      for noninvasive cancer detection based on the molecular-labeled fluorescent
      contrast agents. Recent developments in molecular beacons offer a way to
      selectively tag various precancer and cancer signatures and provide high tumor-to
      background contrast. Near-infrared imaging can deeply probe tissue up to a couple
      of centimeters; thus, it possesses the potential for noninvasive detection of
      breast or lymph node cancer. A phase cancellation (in- and antiphase) device is
      used to increase the sensitivity in detecting fluorescent photons and the
      accuracy of tumor localization. The optoelectronic system consists of the laser
      diode sources, fiber optics, interference filter (to select the fluorescent
      photons), and the high-sensitivity photon detector (photomultiplier tube). The
      source-detector pair scans the tissue surface in multiple directions, and the
      localization image can be obtained by angular back-projection reconstruction.
      Simulations and experimental data demonstrated the feasibility of detection and
      localization offluorescent object embedded inside the highly scattering media.
      Tumor-bearing mouse model with injection of fluorescent contrast agents is used
      to simulate the human breast tumor labeled with molecular beacons. The system can
      detect fluorescent contrast agents as small as one nanomole at the depth of three
      centimeters, with a three-millimeter localization error. This instrument has the
      potential for tumor diagnosis and imaging, and the accuracy of the localization
      suggests that this system could help guide the clinical fine-needle biopsy. Also,
      this portable device would be complementary to x-ray mammography and provide add
      on information on early diagnosis and localization of breast tumor.

PMID- 15742854
TI  - When is a standard not a standard? Differentiating standards, recommended
      practices, and technical information reports.

PMID- 15742855
TI  - Acute respiratory distress syndrome (ARDS) and severe acute respiratory syndrome
      (SARS): are we speaking different languages?

PMID- 15742856
TI  - Clinical features and outcomes of severe acute respiratory syndrome and
      predictive factors for acute respiratory distress syndrome.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious
      disease, and indeed, the SARS epidemic in Taiwan from March to July 2003 had a
      great impact. This study depicts the clinical characteristics and short-term
      outcomes of patients with SARS treated at Taipei Veterans General Hospital;
      potential predictive factors for acute respiratory distress syndrome (ARDS) are
      also analyzed. METHODS: This study retrospectively analyzed data for 67 SARS
      patients, who were grouped according to whether or not ARDS developed during the
      clinical course of SARS. RESULTS: There were 32 males (mean age, 50.3 years;
      range, 20-75 years) and 35 females (mean age, 51.1 years; range, 23-86 years).
      Twenty-five patients (37.3%) were health care workers. At admission, 50 patients
      (74.6%) had abnormal chest radiographs, and all patients developed pulmonary
      infiltrates during the following week. During hospitalization, lymphopenia was
      found in 57 patients (85.1%); and elevated levels of lactate dehydrogenase (LDH;
      n = 55; 83.3%), C-reactive protein (n = 55; 83.3%), aminotransferases (n = 44;
      65.7%), and creatine kinase (n = 14; 20.9%) were also noted. ARDS developed in 33
      patients (49.3%), who were generally older than the patients in whom ARDS did not
      develop, male, non-health care workers, and who generally had dyspnea at the time
      of diagnosis, and a history of diabetes mellitus, hypertension or cerebrovascular
      accident. Patients with, versus those without, ARDS also tended to present with
      more severe lymphopenia and leukocytosis, and with higher levels of LDH and
      aspartate aminotransferase. The overall mortality rate was 31.3% (21/67), whereas
      the rate for patients who developed ARDS was 63.6% (21/33). Multivariate analyses
      showed that age greater than 65 years (odds ratio, OR, 10.6; 95% confidence
      interval, CI, 2.1-54.1), pre-existing diabetes mellitus (OR, 13.7; 95% CI, 1.3
      146.9), and elevated levels of LDH (OR, 8.4; 95% CI, 1.9-36.9) at admission, were
      independent predictors of ARDS. CONCLUSION: The clinical manifestations of SARS
      showed high variability, and were related to the underlying health status of
      individual patients. Importantly, the development of ARDS was associated with
      significant mortality, despite aggressive therapy.

PMID- 15742857
TI  - Non-Hodgkin's lymphoma of the stomach: treatment outcomes for 57 patients over a
      20-year period.
AB  - BACKGROUND: Gastric non-Hodgkin's lymphoma (NHL) is a rare subtype of malignancy,
      for which no consensus exists about treatment. In this study, the treatment
      outcomes of gastric NHL in 57 patients were retrospectively evaluated for a
      period of 20 years at a single institute. METHODS: Clinical stages were
      classified according to the Ann Arbor staging system: 29 patients were stage 1,
      17 stage II, two stage III, and nine stage IV. The 46 stage I/II patients
      received aggressive, multimodal therapy: 24 of these (group A) were treated with
      surgery-based management, which included surgery alone (n = 6), surgery +
      chemotherapy (CT; n = 14), surgery + radiotherapy (RT; n = 2), and surgery + CT +
      RT (n = 2); 22 patients (group B) did not receive surgery, but received CT alone
      (n = 11), CT + RT (n = 5), or, in patients with low-grade mucosa-associated
      lymphoid tissue (MALT) lymphoma, an oral anti-Helicobacter pylori regimen (n =
      6). The 11 stage III/IV patients received CT and/or RT with regimens similar to
      those for stage I/III patients. RESULTS: Except for 1 patient with an initial
      surgical diagnosis, 56 patients underwent gastric endoscopic examination, which
      proved that 42 had NHL. The rate of diagnostic accuracy by gastroscopy was 75%.
      After multimodal treatment (n = 46) and a median follow-up of 54 months (range, 1
      210 months), the 5-year survival rate was 40.3%. The 5-year survival rates for
      stage 1, II and III/IV patients were 57.2%, 47% and 0%, respectively (p < 0.005).
      Of the 24 surgical patients (group A) who received sequential CT, with or without
      RT, 12 remained disease-free after a median follow-up of 98 months (range, 1-210
      months); three patients died because of postoperative complications. Of the 22
      non-surgical patients (group B) who received CT, alone or combined with RT, 14
      remained disease-free after a median follow-up of 40 months (range, 4-189
      months); 1 patient died because of massive gastric hemorrhage after CT. All stage
      III and IV patients died after a median survival of 4 months (range, 1-8 months).
      CONCLUSION: Clinical stage is the most important factor predicting the long-term
      survival of patients with gastric NHL. Surgery may still be necessary in cases of
      failed gastroscopic diagnosis. In early-stage gastric NHL, non-surgical treatment
      seems able to achieve the aims of improved long-term survival and, in some
      instances, cure.

PMID- 15742858
TI  - A longitudinal study of growth patterns in schoolchildren in one Taipei District.
      II: Sitting height, arm span, body mass index and skinfold thickness.
AB  - BACKGROUND: It has been suggested that longitudinal rather than cross-sectional
      growth standards be used to assess individual growth patterns. Thus, the aim of
      this study was to follow boys and girls throughout their pubertal years, so that
      a mixed longitudinal growth curve of height, weight, sitting height, arm span,
      skinfold thickness, body mass index (BMI), and the ratio of sitting height or arm
      span to stature, could be obtained. METHODS: A defined group of 1,139 healthy
      schoolchildren (570 boys and 569 girls) from the Shih-Pai district of Taipei were
      followed longitudinally for 4 years. Anthropometric measurements of height,
      weight, sitting height, arm span, skinfold thickness, and BMI, were obtained for
      each child. RESULTS: Peak sitting-height velocities of 6.1 cm/year (boys) and 6.3
      cm/year (girls) were seen at 8.5 years. The second peak of sitting-height
      velocity occurred at a mean age of 12.5 years for boys and 11.5 years for girls.
      Sitting-height velocity for the whole year covering the second peak was 4.6 cm in
      boys and 3.2 cm in girls. Peak arm-span velocity was seen at 13.5 years for boys
      and 8.5 years for girls, and arm-span velocity for the whole year covering this
      peak was 8.4 cm/year for boys and 8.1 cm/year for girls. CONCLUSION: These data
      provide growth patterns for Chinese children aged 8-18 years living in a Taipei
      district, with percentile charts for sitting height, arm span, BMI, and skinfold
      thickness.

PMID- 15742859
TI  - Internal hernia: computed tomography diagnosis and differentiation from adhesive
      small bowel obstruction.
AB  - BACKGROUND: The goals of this study were to evaluate the specific computed
      tomography (CT) features of internal hernia (IH), and to verify CT features
      useful for the differential diagnosis of IH from adhesive small bowel obstruction
      (ASBO), and for the early detection of intestinal strangulation. METHODS: CT
      findings for 28 patients with surgically proven IH were retrospectively reviewed
      and compared with those for 50 patients with surgically proven ASBO. RESULTS: CT
      features most suggestive of IH versus ASBO included the following: a cluster of
      small bowel segments (100% vs 4% of patients; p < 0.0001); crowding and
      convergence of mesenteric vessels (79% vs 4%; p < 0.0001); mesenteric vessel
      engorgement (79% vs 26%; p = 0.0002); and mass effect to the surrounding bowels
      (82% vs 44%; p = 0.002). In addition, intestinal strangulation, the most severe
      complication, occurred more in IH than ASBO (39% vs 10%; p = 0.002), whereas
      proximal small bowel dilation (46% vs 100%; p < 0.0001) and small-bowel feces
      sign (0% vs 26%; p = 0.0029) were less common in IH than ASBO. The CT features
      indicative of intestinal strangulation were localized mesenteric fluid (p <
      0.0001), mesenteric infiltrates (p = 0.0005), bowel wall thickening (p = 0.003),
      intramural hemorrhage (p = 0.005), mesenteric vessel engorgement (p = 0.03), and
      abnormal bowel wall enhancement (p = 0.008); the first 4 of these features were
      noted more in patients with IH than ASBO. CONCLUSION: The most specific CT
      criteria for the diagnosis of IH, rather than ASBO, were engorged mesenteric
      vessels, mass effect to surrounding organs, and bowel wall thickening. When
      associated mesenteric infiltrates were found, intestinal strangulation was highly
      suspected.

PMID- 15742860
TI  - Treatment of emphysematous pyelonephritis with broad-spectrum antibacterials and
      percutaneous renal drainage: an analysis of 10 patients.
AB  - BACKGROUND: This retrospective study was designed to determine the efficacy of
      broad-spectrum antibacterials combined with percutaneous renal drainage in the
      treatment of emphysematous pyelonephritis (EPN). METHODS: From July 1992 to
      September 2002, 10 patients (nine females and one male) with EPN were managed at
      our institution. All patients had diabetes and presented with fever and chills,
      flank pain or tenderness, vomiting, and altered consciousness. The diagnosis of
      EPN was confirmed by the presence of intraparenchymal and/or perinephric gas in
      imaging studies (kidney-ureter-bladder film, sonogram, and/or computed tomography
      scan). Broad-spectrum antibacterial therapy, combined with percutaneous renal
      drainage, was started in all patients. Follow-up studies consisted of computed
      tomography scan and technetium-labeled diethylenetriaminepentaacetic acid (DTPA)
      radioisotope renography. RESULTS: The outcome was good in all patients. Three
      patients underwent delayed nephrectomy due to non-functioning of the involved
      kidney. The DTPA radioisotope renography results (glomerular filtration rate of
      the diseased kidney/ contralateral healthy kidney) were 0/57 mL/min, 2.7/68.1
      mL/min and 3.7/63.9 mL/min. CONCLUSION: Combined broad-spectrum antibacterial
      therapy and percutaneous renal drainage is a safe and effective treatment for
      EPN, especially in high-risk patients for whom nephrectomy under general
      anesthesia is not feasible.

PMID- 15742861
TI  - Primary pulmonary cryptococcosis presenting as endobronchial tumor with left
      upper lobe collapse.
AB  - Primary pulmonary cryptococcosis is difficult to diagnose because the symptoms
      and radiologic findings are non-specific. Further, pulmonary cryptococcal
      infections are extremely rare in individuals with normal immunity. This case
      report describes a case of primary pulmonary cryptococcosis in an immunocompetent
      individual who presented with left upper lobe collapse due to endobronchial
      occlusion.

PMID- 15742862
TI  - Conservative laparoscopic management of ovarian teratoma torsion in a young
      woman.
AB  - Benign cystic tumors, specifically dermoid or mucinous cysts, are the most
      frequent causes of ovarian torsion. In clinical practice, adnexal torsion is
      usually subjected to adnexectomy to prevent embolism of thrombosed ovarian veins
      and its sequelae. However, this intervention is unsatisfactory for young women
      who want to preserve their fertility. In such situations, conservative management
      with untwisting of the adnexa, followed by cystectomy to preserve part of the
      ovary, would be a better option. In this report, we present a case of adnexal
      torsion due to cystic teratoma. A 25-year-old unmarried woman with lower
      abdominal pain and nausea was referred to our emergency room with suspicion of an
      ovarian mass. Ultrasonography showed a left ovarian mass measuring 9.7 x 6.5 x
      6.2 cm with heterogeneous components within it. Laparoscopy showed an enlarged,
      dusky left ovary with torsion. Detorsion was performed and followed by
      cystectomy. The pathology revealed cystic teratoma of the ovary. We report this
      case to emphasize that untwisting of potentially viable adnexa, followed by
      cystectomy, in patients with adnexal torsion appears to be a safe procedure. This
      conservative approach should be encouraged in women of childbearing age to reduce
      the possibility of premenopausal loss of ovarian function.

PMID- 15742863
TI  - Spinal cord hemangioblastoma with extensive syringomyelia.
AB  - We present the case of a 20-year-old male with intermittent right upper extremity
      numbness for 3 months. His pain perception and temperature sensation were
      severely disturbed. An incidental magnetic resonance imaging (MRI) finding of one
      small intramedullary enhancing nodule at spinal cord level T10-11 with long
      segment syrinx formation suggested the diagnosis of spinal hemangioblastoma with
      syringomyelia. Surgical removal of the tumor and decompression of the spinal cord
      with opening of the syrinx were performed smoothly, and the pathology confirmed
      the diagnosis of spinal hemangioblastoma. Reviewing the literature, MRI is the
      examination of choice for spinal hemangioblastomas, and is helpful in
      preoperative planning and the differential diagnosis of spinal cord neoplasms and
      vascular lesions.

PMID- 15742864
TI  - Epithelioid hemangioendothelioma of the nasal cavity.
AB  - Epithelioid hemangioendothelioma (EH) is an unusual vascular neoplasm
      characterized by proliferation of endothelial cells with epithelioid morphology.
      It has an indolent course, with the potential for recurrence, but rarely
      metastasizes. The common locations include soft tissue, skin, viscera and bone.
      We present an unusual case of EH in the nasal cavity and describe the clinical
      characteristics, histopathologic findings, differential diagnosis and management.
      The 25-year-old male patient initially presented with an 8-month history of
      intermittent epistaxis. Nasal endoscopy revealed a vascular tumor involving the
      nasal cavity. The tumor was excised and the final histopathologic diagnosis was
      consistent with EH. EH in the head and neck is extremely rare. Wide excision is
      the treatment of choice, and regular follow-up is suggested due to the potential
      for recurrence. Definitive diagnosis depends on histopathologic and
      immunohistochemical features.

PMID- 15742865
TI  - Serological screening for MHC (B)-polymorphism in indigenous chickens.
AB  - As part of a series of studies to characterize innate and specific immune
      responses of indigenous chicken lines, birds from Bolivia and India were screened
      serologically for MHC class IV (BG) polymorphism by direct haemagglutination
      using haplotype-specific antisera (B2, B4, B12, B13, B14, B15, B19, B21). The
      sample consisted of 95 Bolivian indigenous chickens and 119 hens from the four
      most common North Indian 'back-yard' chicken lines: Yellow Aseel (AP), Kadaknath
      (KN), frizzled typed (Ff-) and naked neck (NN). Of all chickens tested, the
      majority were haplotyped as B2, B15, B19 and B21. Of the Bolivian chickens, 89.5%
      could be haplotyped: 54.9% were homozygous (including 43.3% B15), and 34.6% were
      heterozygous (including 15.7% B15). B2-like haplotypes were not found among the
      Bolivian hens, and only 3.2% of these birds showed homozygous B21-like proteins.
      Of the Indian hens, MHC (BG)-like proteins could be detected in 60.0% of the AP
      birds, 6.7% of the KN birds; 40.0% of the Ff- birds; and 10.3% of the NN birds.
      In these lines, a total of 40.1% (AP), 6.7% (KN), 30.1% (Ff-) and 10.3% (NN) were
      homozygous for the B-haplotype. Only in the AP line (19.9%), and the Ff- line
      (9.9%) were heterozygous B-haplotypes types found. The B2 haplotype was found in
      all Indian chicken lines. Most Indian birds have completely unknown haplotypes,
      indicating a potentially interesting genetic pool. Subgrouping the Bolivian and
      Indian indigenous hens into monomorphic BG populations revealed individual
      differences based on the B-types.

PMID- 15742866
TI  - Ag-ELISA and PCR for monitoring the vaccination of cattle against Taenia saginata
      cysticercosis using an oncospheral adhesion protein (HP6) with surface and
      secreted localization.
AB  - A Taenia saginata oncosphere-derived adhesion protein (HP6) with surface and
      secreted localization was used to successfully vaccinate calves against oral
      challenge with T. saginata eggs. In contrast, vaccination using a combination of
      T. saginata oncosphere-derived peptides, selected on the basis of their antigenic
      index, and including three derived from the HP6 molecule (HP6-1, HP6-2 and HP6
      3), was unsuccessful. This either indicated that the wrong peptides were selected
      or, in the case of the HP6 protein, that the protective epitope is conformational
      in nature. The protection experiments were monitored using a parasite antigen
      detection ELISA (HP10 Ag-ELISA), which allowed the early determination of the
      success of the vaccination protocol, subsequently confirmed at autopsy. PCR
      assays were used for the first time to confirm the presence of T. saginata DNA in
      lesions recovered at autopsy and thus verify the parasite origin of the lesions.

PMID- 15742867
TI  - Serological survey of Babesia bovis and Anaplasma marginale in cattle in Tete
      Province, Mozambique.
AB  - A serological survey of bovine babesiosis and anaplasmosis in communal cattle was
      conducted in the northwestern province of Tete, Mozambique. Blood was collected
      from cattle ranging from 4 to 15 months old from randomly selected farms from six
      districts. Thirty-nine per cent of all 478 calves tested in Tete Province were
      seropositive to the ELISA for Babesia bovis antibodies and 63% of all calves were
      seropositive in the card agglutination test for Anaplasma marginale.
      Seroprevalence of B. bovis ranged from 22.8% in Tete City District to 48.1% in
      Angonia District. For A. marginale, it ranged from 34.4% in Angonia District to
      87.3% in Moatize District. The dominant factor affecting seroprevalence for both
      haemoparasites was district and there was a trend for higher intensity of tick
      control to be associated with a higher seroprevalence of B. bovis and a lower
      seroprevalence of A. marginale. The obvious differences were the low prevalence
      of B. bovis in Tete City Council District and the low prevalence of A. marginale
      in Angonia District. The levels of exposure to B. bovis seen in our study are
      well below any that could be considered to be consistent with endemic stability,
      yet they are sufficiently high to ensure that clinical disease would be a risk.
      The seroprevalence of A. marginale, however, suggests that endemic stability with
      respect to this disease could exist in districts other than Angonia. There was no
      strong and consistent relationship between the intensity of control and the
      likelihood of seropositivity to either of the diseases.

PMID- 15742868
TI  - Prevalence of the proventricular nematode Tetrameres americana Cram (1927) in
      different age groups of chickens in the Morogoro region, Tanzania.

PMID- 15742869
TI  - Response of laying hens and growing broilers to the dietary inclusion of mango
      (Mangifera indica L.) seed kernel meal.
AB  - Studies were carried out to assess the nutritive value and utilization of mango
      (Mangifera indica L.) seed kernel (MSK) in the diets of layer and broiler
      chickens. The physical component of mango seeds was found to consist of 678 g/kg
      kernel, 292 g/kg shell and 30 g/kg testa. Meal from the seed kernel contained
      61.6 g crude protein, 136.2 g ether extract, 22.3 g ash, 46.4 g crude fibre,
      673.5 g nitrogen-free extract and appreciable mineral content. In the layers
      trial, MSK replaced maize weight for weight at 0, 50, 100, 150, 200 and 250 g/kg.
      Results indicated a significant decrease (p < 0.05) in feed intake, rate of lay,
      egg mass and feed efficiency with increase in MSK. Layers on 150, 200 and 250
      g/kg MSK exhibited the highest body weight losses. Except for lower shell
      thickness (p < 0.05) in hens fed MSK at 200 and 250 g/kg, the internal egg
      quality characteristics were comparable. In the broiler experiment, MSK was
      incorporated at levels of 0, 50, 100, 150 and 200 g/kg at the expense of maize
      but with slight adjustments to the soybean meal so as to achieve isonitrogenous
      diets. Body weight and body weight gains increased significantly (p <0.05) up to
      100 g/kg and then decreased. MSK at 150 or 200 g/kg had no significant effects (p
      >0.05) on feed intake and feed efficiency when compared with control diet. Organ
      weights with the exception of liver and lung were unaffected by dietary MSK.
      Haematological indices were not influenced (p > 0.05) by dietary MSK except
      haemoglobin and mean cell haemoglobin, which were higher (p<0.05) in broilers fed
      100 g/kg MSK. Neutrophils, lymphocytes and albumin/ globulin ratio were similar
      on all diets. The results indicated that at higher weight for weight levels, MSK
      cannot readily substitute maize in layer diets, whereas a marginal improvement
      was recorded in the broiler diet, albeit with nutrient supplementation.

PMID- 15742870
TI  - Preweaning productivity of suckling goats and sheep in Guadeloupe (FWI) under
      intensive reproductive rate and grazing management.
AB  - In Guadeloupe, small ruminants are reared for meat production under pasture
      conditions. Intensive rotative grazing systems (irrigated, fertilized and high
      stocked tropical pastures) allow satisfactory levels of production but generate
      high post-grazing residues. Experiments were designed to control these. A system
      in which residuals were mown (RM) was tested in comparison to the control system
      (residuals remained, RR). The same design was carried out over two years with
      Creole goats and Martinik sheep. An accelerated reproductive rate (3 parturitions
      over 2 years) was carried out. Systems were compared at three parturition seasons
      per year (dry, intermediate and rainy seasons). Each group was composed of 20
      goats (36.0+/-2.5 kg) or 20 ewes (46.8+/-2.4 kg). The systems exhibited high
      levels of productivity in both species compared to other results in the tropics:
      more than 50 and 30 offspring born alive per hectare and per reproductive season
      for the goat and ewe flocks, respectively. The annual production at birth was 110
      kg kids/ha per year and 133 kg lambs/ha per year (i.e. 21% more). Corresponding
      values at weaning were 630 kg kids/ha per year and 785 kg lambs/ha per year (i.e.
      25% more). The RM system produced 10% more than the RR system in Creole goats,
      while it produced 35% more in Martinik sheep. Seasonal effects and other factors
      of variation are discussed.

PMID- 15742871
TI  - Artificial insemination using local cattle breeds in Niger.

PMID- 15742872
TI  - Advances in electrical and mechanical cardiac mapping.
AB  - Cardiac mapping--recording cardiac activity during electrophysiological testing-
      has evolved into an indispensable tool in studying the cardiac excitation
      process, analysing activation patterns, and identifying arrhythmogenic tissue.
      Cardiac mapping is a broad term that is used here to encompass applications that
      record electrical or mechanical activity of the heart or both. In recent years,
      simultaneous and sequential electrical mapping methods have been combined with
      direct mechanical measurements or imaging techniques to acquire information
      regarding both the electrical and mechanical activity of the heart
      (electromechanical mapping) during normal and irregular cardiac behavior. This
      paper reviews the emerging area of electromechanical mapping from the point of
      view of the applicable technology, including its history and application.

PMID- 15742873
TI  - Independent component analysis for biomedical signals.
AB  - Independent component analysis (ICA) is increasing in popularity in the field of
      biomedical signal processing. It is generally used when it is required to
      separate measured multi-channel biomedical signals into their constituent
      underlying components. The use of ICA has been facilitated in part by the free
      availability of toolboxes that implement popular flavours of the techniques.
      Fundamentally ICA in biomedicine involves the extraction and separation of
      statistically independent sources underlying multiple measurements of biomedical
      signals. Technical advances in algorithmic developments implementing ICA are
      reviewed along with new directions in the field. These advances are specifically
      summarized with applications to biomedical signals in mind. The basic assumptions
      that are made when applying ICA are discussed, along with their implications when
      applied particularly to biomedical signals. ICA as a specific embodiment of blind
      source separation (BSS) is also discussed, and as a consequence the criterion
      used for establishing independence between sources is reviewed and this leads to
      the introduction of ICA/BSS techniques based on time, frequency and joint time
      frequency decomposition of the data. Finally, advanced implementations of ICA are
      illustrated as applied to neurophysiologic signals in the form of electro
      magnetic brain signals data.

PMID- 15742874
TI  - Evaluation of potentially significant increase of lead in the blood during long
      term bed rest and space flight.
AB  - We address a gap in the knowledge of lead turnover under conditions of prolonged
      bed rest and microgravity by developing a quantitative model of the amount of
      lead returned to blood circulation from bone. We offer the hypothesis that
      skeletal unloading, such as typically occurs during extended bed rest or
      microgravity, will result in bone lead being released to the blood, as has
      already been demonstrated in the case of calcium. We use initial bone lead
      concentrations to develop predictive models of blood lead elevation. Our
      theoretical calculations with typical bone lead loads measured in today's 40-60
      year-old generation, suggest that the estimated blood lead concentrations in long
      duration (e.g., 100 days) space flight could average between 20 and 40 microg dl(
      1), a range with well-established toxic effects. For a similar duration of bed
      rest, estimated blood lead concentration could be as high as 10-20 microg dl(-1),
      which is a level of concern, particularly if we consider females of childbearing
      age. The preliminary experimental results were obtained under multi-institutional
      collaborations, with the main outcome received from an on-going bed rest study,
      Prevention of Microgravity-Induced Stone Risk by KMgCitrate, conducted at the
      General Clinical Research Center (GCRC) of the University of Texas Southwestern
      Medical Center, Dallas. Based on theoretical modeling and some preliminary
      experimental results, this concept may have important clinical implications by
      allowing prediction of the magnitude of blood lead elevation, thereby
      establishing the means to prevent lead toxicity during long duration space flight
      of astronauts and in conditions of prolonged bed rest such as complicated
      pregnancy, spinal cord injury induced paralysis and comatose patients.

PMID- 15742875
TI  - Effects of viscoelasticity on volume distribution in a two-compartmental model of
      normal and sick lungs.
AB  - Among the models describing respiratory mechanics none has been published with
      the characteristics of two lung compartments including the viscoelastic
      properties. We used such a model to describe the inspiratory compartmental volume
      distribution under homogeneous and inhomogeneous conditions. The present
      mathematical model was tested against actual data and proven accurate. The volume
      distribution was studied using data from normal subjects and from patients with
      COPD and ARDS. In a normal lung, changes in viscoelastic constants in one
      compartment can modify substantially the volume distribution diverting more or
      less gas to the other compartment. In diseased compartments, the increase of
      viscoelasticity increased the difference between the compartments and the
      opposite was true in the less affected compartment. In conclusion, the
      viscoelastic properties are of paramount importance in determining gas
      distribution in normal and sick lungs.

PMID- 15742876
TI  - Exercise-induced respiratory resistance changes as measured with the airflow
      perturbation device.
AB  - Respiratory resistance (Rrs) changes during physical labor can modify the work of
      breathing and thus influence the time that the labor can be performed. Ideal in
      vivo human respiratory performance measurements should have fine temporal
      resolution and minimally impact the respiratory system itself. The airflow
      perturbation device (APD) provides respiratory resistance measurements in this
      manner. Pre-exercise Rrs was compared with post-exercise Rrs, continuously
      monitored for 6 min in 12 non-asthmatic subjects. Rrs following exercise at 70
      75% VO2max was below pre-exercise levels for 40 s into recovery (p < 0.05) and
      inhalation resistance differed more markedly than exhalation resistance. The same
      post-exercise Rrs decline was found when Rrs measurements were compared to those
      taken during flow rates comparable to those found late in recovery. Results
      indicate that (1) Rrs indeed declines following exercise in non-asthmatic
      subjects, probably due to bronchial dilation, (2) Rrs changes can occur on short
      time scales, (3) Rrs changes are not related primarily to flow rate.

PMID- 15742877
TI  - The corner frequencies of the ECG amplifier for heart rate variability analysis.
AB  - Heart rate variability (HRV) analysis is considered a popular method both in
      clinical and research fields. However, several ignored technical artifacts may
      falsify its measurements. The current study investigates the effects of corner
      frequencies of the ECG amplifier on the precision of RR-interval detection. Clear
      or noise-corrupted ECG records with predefined parameters consisting of 21 cycles
      were generated, played back through analog filters and data-logged on a Pentium
      based computer with a DaqBoard2000 data acquisition card. 0.1-10 Hz second-order
      high pass and 20-100 Hz fourth-order low pass Bessel and Butterworth filters were
      used. The RR-intervals were measured between seven reference points of the
      ventricular complexes before and after filtering. High and low pass at every
      frequency cutoff and with both filter types results in correct RR-intervals
      within 1 ms error. However, a lower cutoff below 1 Hz is needed to maintain ECG
      morphology. AC interference or Gaussian random noise can falsify the measured RR
      intervals up to 16 or 34 ms, respectively. These errors may be reduced to 1-4 ms
      with appropriate low pass filters. A frequency range of 0.5-20 Hz for the ECG
      amplifier can be sufficient for HRV analysis reducing the errors from AC
      interference or random noise.

PMID- 15742878
TI  - Human plasma modifications induced by total joint replacement: analysis by
      Fourier transform infrared spectroscopy.
AB  - To better understand the events occurring after major surgery, we examined the
      plasma content of 40 patients undergoing elective total joint replacement. For
      this study, we used Fourier transform infrared (FT-IR) spectroscopy, a
      nondestructive and sensitive technique, to analyse changes in the vibrational
      spectra of plasma samples. Important metabolic changes were observed. Both lipid
      and protein levels were globally decreased one day after surgery as compared with
      preoperative levels. In contrast, triglyceride, glycerol, saccharide and amino
      acid contents were largely increased one day after surgery. Moreover, we detected
      a specific 1180-945 cm(-1) spectral window, which allows good separation of
      patient sera before surgery from patient sera one day after surgery. One week
      after surgery, the biochemical changes were not entirely reversed. Thus, FT-IR
      spectroscopy appears to be a rapid useful tool to investigate the metabolic
      alterations induced by surgery and the recovery period, and to correlate them
      with biochemical and physiological data.

PMID- 15742879
TI  - Measurement of temperature-dependent specific heat of biological tissues.
AB  - We measured specific heat directly by heating a sample uniformly between two
      electrodes by an electric generator. We minimized heat loss by styrofoam
      insulation. We measured temperature from multiple thermocouples at temperatures
      from 25 degrees C to 80 degrees C while heating the sample, and corrected for
      heat loss. We confirm method accuracy with a 2.5% agar-0.4% saline physical model
      and obtain specific heat of 4121+/-89 J (kg K)(-1), with an average error of
      3.1%.

PMID- 15742880
TI  - Non-invasive, side-selective nasal airflow monitoring.
AB  - Nasal obstruction disturbs comfort during daytime, and sleep quality. Convenient
      objective assessment of nasal ventilation would be desirable. Therefore, we
      developed a technique for unobtrusive monitoring of bilateral nasal airflow.
      Nasal cannulae with separated left- and right-sided tubings were connected to two
      pressure transducers. Calibration tables were obtained by recording left and
      right nasal pressures during sequential unilateral nasal occlusion over a few
      breaths along with airflow by a flow meter attached to a mask. Based on these
      data, nasal pressures subsequently provided side-selective estimates of airflow
      without need for a mask. Accuracy of left and right nasal pressure derived
      airflows was evaluated by comparison of their sum to a flow meter in a bench
      model, in five volunteers at baseline and during unilateral nasal obstruction by
      histamine and in five patients during overnight sleep. In the model and
      volunteers, nasal pressure and flow meter derived flow agreed closely at
      baseline, and during partial nasal obstruction that altered left/right nasal flow
      ratios. In patients, nasal pressure derived tidal volumes accurately tracked flow
      meter estimates over >6 h (70 comparisons, bias -1%, limits of agreement +/-19%).
      The described method allows continuous, side-selective and unobtrusive monitoring
      of nasal ventilation for diagnostic evaluation and assessment of treatment
      effects.

PMID- 15742881
TI  - An implantable bi-directional wireless transmission system for transcutaneous
      biological signal recording.
AB  - This study presents an implantable microcontroller-based bi-directional
      transmission system with an inductive link designed for biological signal
      sensing. The system comprises an external module and an implantable module. The
      external module incorporates a high-efficiency class-E transceiver with amplitude
      modulation scheme and a data recovery reader. The transceiver sends both power
      and commands to the implanted module, while the reader recovers the recorded
      biological signal data and transmits the data to a personal computer (PC) for
      further data processing. To reduce the effects of interference induced by the 2
      MHz carrier signal, the implanted module uses two separate coils to perform the
      necessary two-way data transmission. The outward backward telemetry circuitry of
      the implanted module was based on the loadshift keying (LSK) technique. The
      transmitted sensed signal had a 10-bit resolution and a read-out rate of 115
      kbps. The implanted module, measuring 4.5 x 3 x 1.2 cm3, was successfully
      verified in animal experiment in which the electroneurogram (ENG) signal was
      recorded from the sciatic nerve of New Zealand rabbits in response to nociceptive
      stimulation of foot. The reliable operating distance of the system was within
      about 3.5 cm with an efficiency of around 25%. Our present study confirms that
      the proposed biological signal sensing device is suitable for various implanted
      applications following an appropriate biocompatible packaging procedure.

PMID- 15742882
TI  - The eccentric position of the heart in the mammalian body and optimal energy
      transfer in single tube models.
AB  - Many phenomena cannot be explained by traditional haemodynamics models. For
      example, the hearts of all mammals are neither at one end of the circulatory
      system nor at the geometric centre. Based on a new circulation model, we report
      that if the heart is located at either of these two positions, the energy saving
      rule will be violated. We assume that the main arterial system is under a steady,
      distributed transverse vibration with the heart as the input power source. The
      equation of motion of the artery is governed by a new pressure wave equation with
      total energy. We analyse the effects of the heart position on the pressure pulse
      shape and the spectrum. By a simplifying T-tube model, we find that there are
      many harmonic oscillating modes for the overall arterial system. The position of
      the heart affects the weights of different modes. If the heart is at the midpoint
      or at one end of the body, none of the even harmonic modes can be excited. If the
      heart is at a third along the whole system, the third oscillation mode in the
      system is missing. Thus, from an efficiency point of view, this model gives a
      strong reason for all mammals' hearts being at an eccentric position. Tube
      simulations were carried out to confirm the theoretical prediction. A new
      standing wave model to analyse the variation of the pressure pulse shape along
      the artery is discussed. The interesting result indicates that our new pressure
      wave equation possesses a high problem solving potential. It provides a new tool
      for studying arterial dynamics.

PMID- 15742883
TI  - General discrete modelling of lung sound production in normal subjects.
AB  - Lung sound analysis is of a major importance in diagnostic malfunctions of the
      respiratory system. In normal subjects, it is known that these sounds are caused
      by the interaction of the respiratory flows with the bronchial tree structure.
      However, the detailed knowledge of the reasons for the spectral characteristics
      of such sounds remains to be elucidated. In this paper we propose a model for
      normal lung sound production based on a discretization of air flow in particle
      like elements. Their transport with the involved interactions is implemented
      using a pseudo-molecular dynamics Monte Carlo procedure. General physical
      principles were considered for the interaction of these elements with the
      bronchial tree as well as a two-body interaction potential. The particle-tree
      interactions and the particle-particle interactions represent the flow-tree and
      the internal flow interactions, respectively. According to the model, sound is
      produced in each bronchus with the pitch frequency inversely proportional to its
      dimensions and with amplitude proportional to the intensity of the interaction,
      also a function of the bronchus dimensions. The lung sound is then the
      composition of the sounds produced in each bronchus. The model was successful in
      approximating the spectral characteristics reported by Gavriely et al (1981,
      1995) as a direct consequence of the fractal properties of the bronchial tree and
      the considered internal fluid interactions. Thus, the reported high-frequency
      spectrum with its affine property as well as the low-frequency irregularity could
      be reproduced.

PMID- 15742884
TI  - Premature ventricular contraction classification by the Kth nearest-neighbours
      rule.
AB  - An analysis of electrocardiographic pattern recognition parameters for premature
      ventricular contraction (PVC) and normal (N) beat classification is presented.
      Twenty-six parameters were defined: 11 x 2 for the two electrocardiogram (ECG)
      leads, width of the complex and three parameters derived from a single-plane
      vectorcardiogram (VCG). Some of the parameters include amplitudes of maximal
      positive and maximal negative peaks, area of absolute values, area of positive
      values, area of negative values, number of samples with 70% higher amplitude than
      that of the highest peak, amplitude and angle of the QRS vector in a VCG plane.
      They were measured for all heartbeats annotated as N or PVC in all 48 ECG
      recordings of the MIT-BIH arrhythmia database. Two reference sets for the Kth
      nearest-neighbours rule were used-global and local. The classification indices
      obtained with the global reference set were 75.4% specificity and 80.9%
      sensitivity. Using the local reference set we increased the specificity to 96.7%
      and the sensitivity to 96.9%. The achieved specificity and sensitivity are
      comparable with, and greater than, the results reported in the literature.

PMID- 15742885
TI  - Cerebral tissue oxygenation in reversible focal ischemia in rats: multi-site EPR
      oximetry measurements.
AB  - Multi-site electron paramagnetic resonance (EPR) oximetry was used in vivo to
      measure the partial pressure of oxygen (pO2) in reversible focal ischemia in
      rats. The cerebral tissue pO2 was measured simultaneously and continuously at two
      sites on the ischemic side and one on the normal side of the brain in the same
      animal prior to and at several time points after ischemia and reperfusion. The O2
      at the three different sites in brain was stable over 30 min of baseline
      measurements. During the first 120 min of ischemia, statistically significant
      decreases in brain pO2 from baseline were consistently observed in the ischemic
      core and perifocal area. The mean values varied during the 120 min of ischemia.
      Reperfusion resulted in an immediate increase in PO2, but there were no
      significant differences between the sites over time. The result of this study
      seems promising for the study of ischemia and reperfusion. It appears that the
      technique can provide information on the PO2 under the experimental conditions
      needed for such a study. The levels of PO2 that occurred in these experiments are
      readily resolvable by multi-site EPR oximetry. In addition, the ability
      simultaneously to measure the pO2 in several sites provides important additional
      information that should help to differentiate between changes in the PO2 due
      toglobal or local mechanisms.

PMID- 15742886
TI  - Simple instrument for measuring cervical dilatation during labour.
AB  - The construction of a simple disposable instrument for the measurement of
      cervical dilatation is described. The instrument consists of two clips, a
      measuring tape and a flexible tube. The measuring tape is fixed to one clip and
      threaded through the flexible tube, which is fixed to the other clip. The clips
      are attached to opposing cervical rims at 3 o'clock and 9 o'clock and the
      differential displacement of the marking on the measuring tape and free end of
      the flexible tube is measured. Laboratory measurements were performed in order to
      determine the error of measurement. The absolute error of measurement with this
      instrument is 1.5 mm. Clinical measurements were performed on 12 parturients with
      a single foetus in vertex position and 3 to 4 cm cervical dilatation. The results
      of measurements were within +/-1 cm error margin of manual assessments. No
      adverse effects were noted due to the use of the instrument. The instrument did
      cause minor discomfort to patients during application.

PMID- 15742887
TI  - A Bayesian approach to joint feature selection and classifier design.
AB  - This paper adopts a Bayesian approach to simultaneously learn both an optimal
      nonlinear classifier and a subset of predictor variables (or features) that are
      most relevant to the classification task. The approach uses heavy-tailed priors
      to promote sparsity in the utilization of both basis functions and features;
      these priors act as regularizers for the likelihood function that rewards good
      classification on the training data. We derive an expectation-maximization (EM)
      algorithm to efficiently compute a maximum a posteriori (MAP) point estimate of
      the various parameters. The algorithm is an extension of recent state-of-the-art
      sparse Bayesian classifiers, which in turn can be seen as Bayesian counterparts
      of support vector machines. Experimental comparisons using kernel classifiers
      demonstrate both parsimonious feature selection and excellent classification
      accuracy on a range of synthetic and benchmark data sets.

PMID- 15742888
TI  - FloatBoost learning and statistical face detection.
AB  - A novel learning procedure, called FloatBoost, is proposed for learning a boosted
      classifier for achieving the minimum error rate. FloatBoost learning uses a
      backtrack mechanism after each iteration of AdaBoost learning to minimize the
      error rate directly, rather than minimizing an exponential function of the margin
      as in the traditional AdaBoost algorithms. A second contribution of the paper is
      a novel statistical model for learning best weak classifiers using a stagewise
      approximation of the posterior probability. These novel techniques lead to a
      classifier which requires fewer weak classifiers than AdaBoost yet achieves lower
      error rates in both training and testing, as demonstrated by extensive
      experiments. Applied to face detection, the FloatBoost learning method, together
      with a proposed detector pyramid architecture, leads to the first real-time
      multiview face detection system reported.

PMID- 15742889
TI  - An experimental comparison of min-cut/max-flow algorithms for energy minimization
      in vision.
AB  - After [15], [31], [19], [8], [25], [5], minimum cut/maximum flow algorithms on
      graphs emerged as an increasingly useful tool for exact or approximate energy
      minimization in low-level vision. The combinatorial optimization literature
      provides many min-cut/max-flow algorithms with different polynomial time
      complexity. Their practical efficiency, however, has to date been studied mainly
      outside the scope of computer vision. The goal of this paper is to provide an
      experimental comparison of the efficiency of min-cut/max flow algorithms for
      applications in vision. We compare the running times of several standard
      algorithms, as well as a new algorithm that we have recently developed. The
      algorithms we study include both Goldberg-Tarjan style "push-relabel" methods and
      algorithms based on Ford-Fulkerson style "augmenting paths." We benchmark these
      algorithms on a number of typical graphs in the contexts of image restoration,
      stereo, and segmentation. In many cases, our new algorithm works several times
      faster than any of the other methods, making near real-time performance possible.
      An implementation of our max-flow/min-cut algorithm is available upon request for
      research purposes.

PMID- 15742890
TI  - Range image segmentation by an effective jump-diffusion method.
AB  - This paper presents an effective jump-diffusion method for segmenting a range
      image and its associated reflectance image in the Bayesian framework. The
      algorithm works on complex real-world scenes (indoor and outdoor), which consist
      of an unknown number of objects (or surfaces) of various sizes and types, such as
      planes, conics, smooth surfaces, and cluttered objects (like trees and bushes).
      Formulated in the Bayesian framework, the posterior probability is distributed
      over a solution space with a countable number of subspaces of varying dimensions.
      The algorithm simulates Markov chains with both reversible jumps and stochastic
      diffusions to traverse the solution space. The reversible jumps realize the moves
      between subspaces of different dimensions, such as switching surface models and
      changing the number of objects. The stochastic Langevin equation realizes
      diffusions within each subspace. To achieve effective computation, the algorithm
      precomputes some importance proposal probabilities over multiple scales through
      Hough transforms, edge detection, and data clustering. The latter are used by the
      Markov chains for fast mixing. The algorithm is tested on 100 1D simulated data
      sets for performance analysis on both accuracy and speed. Then, the algorithm is
      applied to three data sets of range images under the same parameter setting. The
      results are satisfactory in comparison with manual segmentations.

PMID- 15742891
TI  - Simultaneous feature selection and clustering using mixture models.
AB  - Clustering is a common unsupervised learning technique used to discover group
      structure in a set of data. While there exist many algorithms for clustering, the
      important issue of feature selection, that is, what attributes of the data should
      be used by the clustering algorithms, is rarely touched upon. Feature selection
      for clustering is difficult because, unlike in supervised learning, there are no
      class labels for the data and, thus, no obvious criteria to guide the search.
      Another important problem in clustering is the determination of the number of
      clusters, which clearly impacts and is influenced by the feature selection issue.
      In this paper, we propose the concept of feature saliency and introduce an
      expectation-maximization (EM) algorithm to estimate it, in the context of mixture
      based clustering. Due to the introduction of a minimum message length model
      selection criterion, the saliency of irrelevant features is driven toward zero,
      which corresponds to performing feature selection. The criterion and algorithm
      are then extended to simultaneously estimate the feature saliencies and the
      number of clusters.

PMID- 15742892
TI  - Simultaneous two-view epipolar geometry estimation and motion segmentation by 4D
      tensor voting.
AB  - We address the problem of simultaneous two-view epipolar geometry estimation and
      motion segmentation from nonstatic scenes. Given a set of noisy image pairs
      containing matches of n objects, we propose an unconventional, efficient, and
      robust method, 4D tensor voting, for estimating the unknown n epipolar
      geometries, and segmenting the static and motion matching pairs into n
      independent motions. By considering the 4D isotropic and orthogonal joint image
      space, only two tensor voting passes are needed, and a very high noise to signal
      ratio (up to five) can be tolerated. Epipolar geometries corresponding to
      multiple, rigid motions are extracted in succession. Only two uncalibrated frames
      are needed, and no simplifying assumption (such as affine camera model or
      homographic model between images) other than the pin-hole camera model is made.
      Our novel approach consists of propagating a local geometric smoothness
      constraint in the 4D joint image space, followed by global consistency
      enforcement for extracting the fundamental matrices corresponding to independent
      motions. We have performed extensive experiments to compare our method with some
      representative algorithms to show that better performance on nonstatic scenes are
      achieved. Results on challenging data sets are presented.

PMID- 15742893
TI  - Utilization of hierarchical, stochastic relationship modeling for Hangul
      character recognition.
AB  - In structural character recognition, a character is usually viewed as a set of
      strokes and the spatial relationships between them. Therefore, strokes and their
      relationships should be properly modeled for effective character representation.
      For this purpose, we propose a modeling scheme by which strokes as well as
      relationships are stochastically represented by utilizing the hierarchical
      characteristics of target characters. A character is defined by a multivariate
      random variable over the components and its probability distribution is learned
      from a training data set. To overcome difficulties of the learning due to the
      high order of the probability distribution (a problem of curse of
      dimensionality), the probability distribution is factorized and approximated by a
      set of lower-order probability distributions by applying the idea of relationship
      decomposition recursively to components and subcomponents. Based on the proposed
      method, a handwritten Hangul (Korean) character recognition system is developed.
      Recognition experiments conducted on a public database show the effectiveness of
      the proposed relationship modeling. The recognition accuracy increased by 5.5
      percent in comparison to the most successful system ever reported.

PMID- 15742894
TI  - Onvergence and application of online active sampling using orthogonal pillar
      vectors.
AB  - The analysis of convergence and its application is shown for the Active Sampling
      at-the-Boundary method applied to multidimensional space using orthogonal pillar
      vectors. Active learning method facilitates identifying an optimal decision
      boundary for pattern classification in machine learning. The result of this
      method is compared with the standard active learning method that uses random
      sampling on the decision boundary hyperplane. The comparison is done through
      simulation and application to the real-world data from the UCI benchmark data
      set. The boundary is modeled as a nonseparable linear decision hyperplane in
      multidimensional space with a stochastic oracle.

PMID- 15742895
TI  - Tracking multiple humans in complex situations.
AB  - Tracking multiple humans in complex situations is challenging. The difficulties
      are tackled with appropriate knowledge in the form of various models in our
      approach. Human motion is decomposed into its global motion and limb motion. In
      the first part, we show how multiple human objects are segmented and their global
      motions are tracked in 3D using ellipsoid human shape models. Experiments show
      that it successfully applies to the cases where a small number of people move
      together, have occlusion, and cast shadow or reflection. In the second part, we
      estimate the modes (e.g., walking, running, standing) of the locomotion and 3D
      body postures by making inference in a prior locomotion model. Camera model and
      ground plane assumptions provide geometric constraints in both parts. Robust
      results are shown on some difficult sequences.

PMID- 15742896
TI  - A unified framework for subspace face recognition.
AB  - PCA, LDA, and Bayesian analysis are the three most representative subspace face
      recognition approaches. In this paper, we show that they can be unified under the
      same framework. We first model face difference with three components: intrinsic
      difference, transformation difference, and noise. A unified framework is then
      constructed by using this face difference model and a detailed subspace analysis
      on the three components. We explain the inherent relationship among different
      subspace methods and their unique contributions to the extraction of
      discriminating information from the face difference. Based on the framework, a
      unified subspace analysis method is developed using PCA, Bayes, and LDA as three
      steps. A 3D parameter space is constructed using the three subspace dimensions as
      axes. Searching through this parameter space, we achieve better recognition
      performance than standard subspace methods.

PMID- 15742897
TI  - Extraction of shift invariant wavelet features for classification of images with
      different sizes.
AB  - An effective shift invariant wavelet feature extraction method for classification
      of images with different sizes is proposed. The feature extraction process
      involves a normalization followed by an adaptive shift invariant wavelet packet
      transform. An energy signature is computed for each subband of these invariant
      wavelet coefficients. A reduced subset of energy signatures is selected as the
      feature vector for classification of images with different sizes. Experimental
      results show that the proposed method can achieve high classification accuracy of
      98.5 percent and outperforms the other two image classification methods.

PMID- 15742898
TI  - Minimal representations of 3D models in terms of image parameters under
      calibrated and uncalibrated perspective.
AB  - Indexing is a well-known paradigm for object recognition. In indexing, each 3D
      model is represented as the set of values assumed by a given vector of image
      parameters in correspondence to all the possible images of the 3D model. An open
      problem, posed by Jacobs, concerned the minimum dimensionality of such sets under
      perspective. This paper proves that, under calibrated or uncalibrated
      perspective, the minimum dimensionality of the set representing any 3D modeled
      point-set is two. Two-dimensional representations are found also for 3D curved
      objects.

PMID- 15742899
TI  - A simple technique for improving camera displacement estimation in eye-in-hand
      visual servoing.
AB  - A simple technique for estimating the camera displacement from point
      correspondences in eye-in-hand visual servoing is presented. The idea for
      providing more accurate results than existing methods consists of taking into
      account that the point correspondences used during the camera motion correspond
      to stationary spatial points, hence exploiting additional information. This is
      done by first estimating the object Euclidean structure and then estimating the
      camera displacement from this estimate.

PMID- 15742900
TI  - Distance-preserving projection of high-dimensional data for nonlinear
      dimensionality reduction.
AB  - A distance-preserving method is presented to map high-dimensional data
      sequentially to low-dimensional space. It preserves exact distances of each data
      point to its nearest neighbor and to some other near neighbors. Intrinsic
      dimensionality of data is estimated by examining the preservation of interpoint
      distances. The method has no user-selectable parameter. It can successfully
      project data when the data points are spread among multiple clusters. Results of
      experiments show its usefulness in projecting high-dimensional data.

PMID- 15742901
TI  - Manganese dosimetry: species differences and implications for neurotoxicity.
AB  - Manganese (Mn) is an essential mineral that is found at low levels in food,
      water, and the air. Under certain high-dose exposure conditions, elevations in
      tissue manganese levels can occur. Excessive manganese accumulation can result in
      adverse neurological, reproductive, and respiratory effects in both laboratory
      animals and humans. In humans, manganese-induced neurotoxicity (manganism) is the
      overriding concern since affected individuals develop a motor dysfunction
      syndrome that is recognized as a form of parkinsonism. This review primarily
      focuses on the essentiality and toxicity of manganese and considers contemporary
      studies evaluating manganese dosimetry and its transport across the blood-brain
      barrier, and its distribution within the central nervous system (CNS). These
      studies have dramatically improved our understanding of the health risks posed by
      manganese by determining exposure conditions that lead to increased
      concentrations of this metal within the CNS and other target organs. Most
      individuals are exposed to manganese by the oral and inhalation routes of
      exposure; however, parenteral injection and other routes of exposure are
      important. Interactions between manganese and iron and other divalent elements
      occur and impact the toxicokinetics of manganese, especially following oral
      exposure. The oxidation state and solubility of manganese also influence the
      absorption, distribution, metabolism, and elimination of manganese. Manganese
      disposition is influenced by the route of exposure. Rodent inhalation studies
      have shown that manganese deposited within the nose can undergo direct transport
      to the brain along the olfactory nerve. Species differences in manganese
      toxicokinetics and response are recognized with nonhuman primates replicating CNS
      effects observed in humans while rodents do not. Potentially susceptible
      populations, such as fetuses, neonates, individuals with compromised hepatic
      function, individuals with suboptimal manganese or iron intake, and those with
      other medical states (e.g., pre-parkinsonian state, aging), may have altered
      manganese metabolism and could be at greater risk for manganese toxicity.

PMID- 15742902
TI  - Ochratoxin A: the continuing enigma.
AB  - The mycotoxin ochratoxin A (OTA) has been linked to the genesis of several
      disease states in both animals and humans. It has been described as nephrotoxic,
      carcinogenic, teratogenic, immunotoxic, and hepatotoxic in laboratory and
      domestic animals, as well as being thought to be the probable causal agent in the
      development of nephropathies (Balkan Endemic Nephropathy, BEN and Chronic
      Interstitial Nephropathy, CIN) and urothelial tumors in humans. As a result,
      several international agencies are currently attempting to define safe legal
      limits for OTA concentration in foodstuffs (e.g., grain, meat, wine, and coffee),
      in processed foods, and in animal fodder. In order to achieve this goal, an
      accurate risk assessment of OTA toxicity including mechanistic and
      epidemiological studies must be carried out. Ochratoxin has been suggested by
      various researchers to mediate its toxic effects via induction of apoptosis,
      disruption of mitochondrial respiration and/or the cytoskeleton, or, indeed, via
      the generation of DNA adducts. Thus, it is still unclear if the predominant
      mechanism is of a genotoxic or an epigenetic nature. One aspect that is clear,
      however, is that the toxicity of OTA is subject to and characterized by large
      species- and sex-specific differences, as well as an apparently strict structure
      activity relationship. These considerations could be crucial in the investigation
      of OTA-mediated toxicity. Furthermore, the use of appropriate in vivo and in
      vitro model systems appears to be vital in the generation of relevant
      experimental data. The intention of this review is to collate and discuss the
      currently available data on OTA-mediated toxicity with particular focus on their
      relevance for the in vivo situation, and also to suggest possible future
      strategies for unlocking the secrets of ochratoxin A.

PMID- 15742903
TI  - Role of oxidative stress in peroxisome proliferator-mediated carcinogenesis.
AB  - In this review, the evidence about the role of oxidative stress in the induction
      of hepatocellular carcinomas by peroxisome proliferators is examined. The
      activation of PPAR-alpha by peroxisome proliferators in rats and mice may produce
      oxidative stress, due to the induction of enzymes like fatty acyl coenzyme A
      (CoA) oxidase (AOX) and cytochrome P-450 4A1. The effect of peroxisome
      proliferators on the antioxidant defense system is reviewed, as is the effect on
      endpoints resulting from oxidative stress that may be important in
      carcinogenesis, such as lipid peroxidation, oxidative DNA damage, and
      transcription factor activation. Peroxisome proliferators clearly inhibit several
      enzymes in the antioxidant defense system, but studies examining effects on lipid
      peroxidation and oxidative DNA damage are conflicting. There is a profound
      species difference in the induction of hepatocellular carcinomas by peroxisome
      proliferators, with rats and mice being sensitive, whereas species such as
      nonhuman primates and guinea pigs are not susceptible to the effects of
      peroxisome proliferators. The possible role of oxidative stress in these species
      differences is also reviewed. Overall, peroxisome proliferators produce changes
      in oxidative stress, but whether these changes are important in the carcinogenic
      process is not clear at this time.

PMID- 15742904
TI  - Death certificates: let's get it right.

PMID- 15742905
TI  - Resources for management of cutaneous leishmaniasis.

PMID- 15742906
TI  - Patients' "wants" should not determine decision-making.

PMID- 15742907
TI  - Care of cancer survivors.
AB  - Cancer survivors are at increased risk for recurrence of their original
      malignancy; development of second primary malignancies; and medical,
      developmental, and psychologic problems resulting from cancer therapy, genetic
      predisposition to cancer, and other risk factors. Surveillance following curative
      cancer treatment generally includes interval history and physical examinations
      every six months for five years. Thereafter, histories and examinations are
      recommended annually for breast cancer; every three months for two years, then
      every six months for three to five years for colorectal cancer; and every six
      months for five years, then annually for prostate cancer. Recommended laboratory
      tests and ancillary procedures include annual mammography of preserved breast
      tissue in breast cancer survivors, carcinoembryonic antigen level monitoring in
      conjunction with annual colonoscopy in colorectal cancer patients, and prostate
      specific antigen measurements every six months for five years and then annually
      in prostate cancer survivors. In addition, family physicians should be attentive
      to concerns about altered body image or sexuality issues following curative
      surgical procedures. Continued emphasis on preventive health practices is
      encouraged. Physicians should remain alert to nonspecific symptoms or physical
      findings (e.g., mass, adenopathy) that can indicate cancer recurrence. In
      childhood cancer survivors, periodic evaluation that includes a plan for
      surveillance and prevention, incorporating risks based on previous cancer,
      therapy, genetic predispositions, personal behaviors, and comorbid health
      conditions, is recommended.

PMID- 15742908
TI  - Information from your family doctor. Health care after cancer treatment.

PMID- 15742910
TI  - Information from your family doctor. Cluster headaches.

PMID- 15742909
TI  - Management of cluster headache.
AB  - Cluster headache, an excruciating, unilateral headache usually accompanied by
      conjunctival injection and lacrimation, can occur episodically or chronically,
      and can be difficult to treat. Existing effective treatments may be underused
      because of underdiagnosis of the syndrome. Oxygen and sumatriptan have been
      demonstrated to be effective in the acute treatment of cluster headaches.
      Verapamil has been shown to be effective for prophylaxis. For cluster headache
      completely refractory to all treatments, surgical modalities and newer
      interventions such as the implantation of stereotactic electrodes may be useful.
      Patients should be encouraged to avoid possible triggers such as smoking or
      alcohol consumption, especially during the duster period. The intensity of duster
      headache pain leads to ethical concerns among researchers over the use of
      placebo, making randomized controlled trials difficult. As new technology and
      genetic studies clarify the etiology of duster headache, it is possible that more
      specific therapies will emerge.

PMID- 15742911
TI  - Treatment of panic disorder.
AB  - Panic disorder with or without agoraphobia occurs commonly in patients in primary
      care settings. This article assesses multiple evidence-based reviews of effective
      treatments for panic disorder. Antidepressant medications successfully reduce the
      severity of panic symptoms and eliminate panic attacks. Selective serotonin
      reuptake inhibitors and tricyclic antidepressants are equally effective in the
      treatment of panic disorder. The choice of medication is based on side effect
      profiles and patient preferences. Strong evidence supports the effectiveness of
      cognitive behavior therapy in treating panic disorder. Family physicians who are
      not trained in cognitive behavior therapy may refer patients with panic disorder
      to therapists with such training. Cognitive behavior therapy can be used alone or
      in combination with antidepressants to treat patients with panic disorder.
      Benzodiazepines are effective in treating panic disorder symptoms, but they are
      less effective than antidepressants and cognitive behavior therapy.

PMID- 15742912
TI  - Information from your family doctor. Panic attacks.

PMID- 15742913
TI  - Diagnostic approach to palpitations.
AB  - Palpitations-sensations of a rapid or irregular heartbeat-are most often caused
      by cardiac arrhythmias or anxiety. Most patients with arrhythmias do not complain
      of palpitations. However, any arrhythmia, including sinus tachycardia, atrial
      fibrillation, premature ventricular contractions, or ventricular tachycardia, can
      cause palpitations. Palpitations should be considered as potentially more serious
      if they are associated with dizziness, near-syncope, or syncope. Nonarrhythmic
      cardiac problems, such as mitral valve prolapse, pericarditis, and congestive
      heart failure, and noncardiac problems, such as hyperthyroidism, vasovagal
      syncope, and hypoglycemia, can cause palpitations. Palpitations also can result
      from stimulant drugs, and over-the-counter and prescription medications. No cause
      for the palpitations can be found in up to 16 percent of patients. Ambulatory
      electrocardiographic (ECG) monitoring usually is indicated if the etiology of
      palpitations cannot be determined from the patient's history, physical
      examination, and resting ECG. When palpitations occur unpredictably or do not
      occur daily, an initial two-week course of continuous closed-loop event recording
      is indicated. Holter monitoring for 24 to 48 hours may be appropriate in patients
      with daily palpitations. Trans-telephonic event monitors are more effective and
      cost-effective than Holter monitors for most patients.

PMID- 15742914
TI  - Information from your family doctor. Heart palpitations.

PMID- 15742915
TI  - Evidence-based initiation of warfarin (Coumadin).

PMID- 15742916
TI  - A painless red nodule. Kaposi's sarcoma.

PMID- 15742917
TI  - Enlarged, dark-colored pores on nose. Asymptomatic lesions do not drain any
      sebaceous substance.

PMID- 15742918
TI  - Herbal supplements in older adults. Consider interactions and adverse events that
      may result from supplement use.

PMID- 15742919
TI  - CRT plus ICD in congestive heart failure. Use of cardiac resynchronization
      therapy and an implantable cardioverter-defibrillator in heart failure patients
      with abnormal left ventricular dysfunction.
AB  - Cardiac resynchronization therapy (CRT) significantly improves functional status,
      exercise duration, left ventricular (LV) ejection fraction, death from
      progressive congestive heart failure (CHF), and hospitalization for CHF in
      patients with moderate-to-severe CHF, an abnormal LV ejection fraction, and a QRS
      duration on the electrocardiogram of 120 msec or more. In these patients, CRT
      reduces all-cause mortality, though not significantly. However, CRT plus. an
      implantable cardioverter-defibrillator (ICD) significantly reduces all-cause
      mortality. Compared with placebo, ICD therapy significantly reduced all-cause
      mortality by 33% in patients with class II or III CHF, an abnormal LV ejection
      fraction, and a QRS duration on the electrocardiogram of 120 msec or more.

PMID- 15742920
TI  - Living with heart failure.

PMID- 15742921
TI  - Once upon a time, heart failure was easy.

PMID- 15742922
TI  - Preventive services: screening. Health maintenance examinations include screening
      for diabetes, heart disease, cancer, osteoporosis, hearing and vision loss.

PMID- 15742923
TI  - [Chronic diarrhea and weight loss].

PMID- 15742924
TI  - [Therapeutic options for benign biliary lesions].

PMID- 15742925
TI  - [HIV infection: in the HAART era, CD4 makes the difference].

PMID- 15742927
TI  - [Percutaneous endoscopic gastrostomy in patients with neurological diseases.
      Results of a prospective multicenter and international study].
AB  - AIM: To determine prospectively the long-term evolution of patients with
      neurological diseases after insertion of percutaneous endoscopic gastrostomy
      (PEG). METHODS: 109 PEG were performed in 99 consecutive patients (49 females, 50
      males), mean age 75 years (range: 20-97 years) as an alternative to a nasogastric
      tube. Patients were enterally fed because of chronic neurological swallowing
      difficulties: cerebrovascular disease 38, dementia 27, disordered swallowing
      mechanisms in elderly patients 10, motor neurona disease and multiple sclerosis
      10, neuro-surgical disease 6, Parkinson's disease 3, brain tumor 3, neo-natal
      encephalopathy 1, HIV encephalopathy 1. The procedure took place in a dedicated
      endoscopy room. In all cases, prophylatic antibiotics were given and the PEG tube
      was inserted by the "pull" technique. RESULTS: PEG insertion was technically
      succesful in all cases. After PEG insertion, all patients were subsequently
      discharged to local nursing home facilities. 85/99 patients were long-term
      followed-up on an outpatient basis, 25% of them were followed for more than a
      year. The mean follow-up time was 3 months (range: 1-24 months). The most
      frequent complication were minor: local wound infection 6, ostomy leakage 8,
      silicon degradation 16, leading to the removal of the PEG and the placement of a
      new PEG tubes in 10 cases. Two major complications were observed : one gastric
      perforation and death 2 months after the PEG placement and one gastrocolic
      fistula. No aspiration pneumonia was reported. In one patient, PEG was removed
      after recuperation of a normal swallowing. All patients had a nutritional
      improvement. A total of 11 deaths occurred during the follow-up, related to the
      neurological disorder in 10/11 cases. Nursing home team, patient's physicians and
      patient's families found PEG manipulations easier than naso-gastric tube.
      CONCLUSION: Our study suggests that PEG is a method of choice for enteral feeding
      of patients with chronic neurological disorders. PEG is well-tolerated, leading
      to an improvement in nutritional status and offering good facilities for home
      nursing.

PMID- 15742928
TI  - [Cyclospora cayetanensis in patients with AIDS and chronic diarrhea].
AB  - Cyclospora spp. is a protozoan parasite responsible for significant
      gastrointestinal disease in patients infected with the human immunodeficiency
      virus. We report the clinical features of two patients with chronic diarrhea and
      intestinal cyclosporosis caused by Cyclospora cayetanensis. The average value for
      CD4 count in these patients was lower than or equal to 100 cells/mm3. The oocysts
      were detected in smears from stool samples stained with modified acid-fast or
      safranin technique. Light microscopy revealed parasites in the enterocytes and
      these parasites were associated with villous atrophy. Cyclospora cayetanensis
      infection might be an important cause of diarrhea in patients with AIDS in
      Argentina.

PMID- 15742929
TI  - [Final report of the Argentine Consensus on hepatitis B].

PMID- 15742926
TI  - [Endoscopic approach in HIV infected-patients with upper gastrointestinal
      symptoms].
AB  - Upper gastrointestinal symptoms such as nausea, vomiting, upper abdominal pain,
      heartburn, early satiety, bloating and anorexia, are frequently reported by HIV
      positive patients; however, their prevalence and diagnostic approach are unknown.
      AIMS: To evaluate the frequency of endoscopic and histologic diagnosis in HIV
      positive patients with upper gastrointestinal symptoms referred to upper
      endoscopy, and to compare them with those found in a non-HIV infected group with
      similar symptoms. PATIENTS AND METHODS: Out of 132 HIV positive patients referred
      to upper endoscopy, 102 (75%) with upper gastrointestinal symptoms, and 177 non
      HIV controls were prospectively included. All patients answered questionnaires
      assessing frequency, severity and impact of symptoms on quality of life, and
      underwent upper endoscopy with systematic mucosal biopsies from esophagus,
      stomach and distal duodenum. RESULTS: Upper abdominal pain, heartburn and
      bloating were the most common upper gastrointestinal symptom reported in both
      groups. Anorexia, nausea, vomiting and early satiety were more frequent among HIV
      positive patients (p = or < 0.01). Intensity and impact of symptoms quality of
      life were higher in this group (p = 0.0001). Opportunistic infections were
      detected in 29 (28.4%) HIV positive patients. This subgroup had a lower mean CD4
      count (p = 0.0004). In 76 (75.4%) HIV positive non-opportunistic diseases were
      diagnosed, with similar frequency to HIV negative individuals. CONCLUSIONS: Upper
      endoscopy with biopsies detected opportunistic and non-opportunistic diseases in
      HIV positive patients with upper gastrointestinal symptoms. Opportunistic
      diseases were related to lower CD4 counts. Non-opportunistic diseases had similar
      frequency in both groups, HIV positive and negative controls.

PMID- 15742931
TI  - Editorial: Public policy--House of Lords increases scope for claimants to recover
      damages for negligent failure to warn of treatment risks.

PMID- 15742932
TI  - To find the mind's reflection in the face.

PMID- 15742933
TI  - Brushes with Bolam. Where will it lead?

PMID- 15742934
TI  - The Watson boxer case: what actually happened? What is the significance of what
      actually happened?

PMID- 15742935
TI  - The English tort system for medical mishaps.

PMID- 15742936
TI  - Human Tissue Act 2004: the removal and retention of human organs and tissue.

PMID- 15742937
TI  - Gender reassignment.

PMID- 15742938
TI  - High-resolution PET detector design: modelling components of intrinsic spatial
      resolution.
AB  - The development of dedicated small animal PET (positron emission tomography)
      scanners has led to significantly higher spatial resolution and comparable
      sensitivity to clinical scanners. However, it is not clear whether we are
      approaching the fundamental limit of spatial resolution. This work aims to
      understand what is currently limiting spatial resolution during data formation
      and collection and how to apply that knowledge to obtain the best possible
      resolution for small animal PET without sacrificing sensitivity. Monte Carlo
      simulations were performed of the interactions of a 511 keV photon in a variety
      of detector materials to evaluate the modulation transfer function of the
      materials. Positron range, non-colinearity and pixel size were modelled to
      determine the contribution of additional components of data formation and
      collection on the complete modulation transfer function of a PET system. These
      simulations are shown to predict the intrinsic detector resolution of current
      high resolution systems very well. They also show that current detectors are not
      limited by inter-crystal scatter. An intrinsic resolution of 0.5 mm can be
      achieved, but would require a detector with a pixel size of around 250 microm
      that can be read out unambiguously. It is shown that a range of different
      detector materials, both scintillators and semiconductors, can be used in these
      high-resolution detectors. While this design relies on thin (approximately 3 mm)
      pieces of material, stacks of the material are shown to simultaneously provide
      spatial resolution near 0.5 mm and 60% efficiency. This work has shown that
      detectors with significantly better resolution and sensitivity can be developed
      for small animal PET applications.

PMID- 15742939
TI  - High-frequency ultrasound for monitoring changes in liver tissue during
      preservation.
AB  - Currently the only method to assess liver preservation injury is based on liver
      appearance and donor medical history. Previous work has shown that high-frequency
      ultrasound could detect ischemic cell death due to changes in cell morphology. In
      this study, we use high-frequency ultrasound integrated backscatter to assess
      liver damage in experimental models of liver ischemia. Ultimately, our goal is to
      predict organ suitability for transplantation using high-frequency imaging and
      spectral analysis techniques. To examine the effects of liver ischemia at
      different temperatures, livers from Wistar rats were surgically excised, immersed
      in phosphate buffer saline and stored at 4 and 20 degrees C for 24 h. To mimic
      organ preservation, livers were excised, flushed with University of Wisconsin
      (UW) solution and stored at 4 degrees C for 24 h. Preservation injury was
      simulated by either not flushing livers with UW solution or, before scanning,
      allowing livers to reach room temperature. Ultrasound images and corresponding
      radiofrequency data were collected over the ischemic period. No significant
      increase in integrated backscatter (approximately 2.5 dBr) was measured for the
      livers prepared using standard preservation conditions. For all other ischemia
      models, the integrated backscatter increased by 4-9 dBr demonstrating kinetics
      dependent on storage conditions. The results provide a possible framework for
      using high-frequency imaging to non-invasively assess liver preservation injury.

PMID- 15742940
TI  - Simulation of voltage-sensitive optical signals in three-dimensional slabs of
      cardiac tissue: application to transillumination and coaxial imaging methods.
AB  - Voltage-sensitive dyes are an important tool in visualizing electrical activity
      in cardiac tissue. Until today, they have mainly been applied in cardiac
      electrophysiology to subsurface imaging. In the present study, we assess
      different imaging methods used in optical tomography with respect to their
      effectiveness in visualizing 3D cardiac activity. To achieve this goal, we
      simulate optical signals produced by excitation fronts initiated at different
      depths inside the myocardial wall and compare their properties for various
      imaging modes. Specifically, we consider scanning and broad-field illumination,
      including trans- and epi-illumination. We focus on the lateral optical resolution
      and signal intensity, as a function of the source depth. Optical diffusion theory
      is applied to derive a computationally efficient approximation of the point
      spread function and to predict voltage-sensitive signals. Computations were
      performed both for fluorescent and absorptive voltage-sensitive dyes. Among all
      the above-mentioned methods, fluorescent coaxial scanning yields the best
      resolution (<2.5 mm) and gives the most information about the intramural cardiac
      activity.

PMID- 15742941
TI  - Regional surface geometry of the rat stomach based on three-dimensional curvature
      analysis.
AB  - A better understanding of gastric accommodation and gastric perception requires
      knowledge of regional gastric geometry and local gastric tension throughout the
      stomach. An analytic method based on medical imaging data was developed in this
      study to describe the three-dimensional (3D) rat stomach geometry and tension
      distribution. The surface principal radii of curvatures were simulated and the
      surface tension was calculated in the glandular and non-glandular region of the
      stomach at pressures from 0 Pa to 800 Pa. The radii of curvature and tension
      distribution in the stomach were non-homogeneous. The radii of curvature in the
      glandular stomach were larger than those in the non-glandular region at pressures
      less than 100 Pa (P < 0.001). When the pressure increased to more than 200 Pa,
      the radii of curvature in the non-glandular stomach was larger than in the
      glandular stomach (P < 0.05). The curvature and tension distribution mapping
      using medical imaging technology and 3D models can be used to characterize and
      distinguish the physical behaviour in separate regions of the stomach.

PMID- 15742942
TI  - Diffuse optical tomography using intensity measurements and the a priori acquired
      regions of interest: theory and simulations.
AB  - Light transmission data collected around an object show large variation with
      source-detector separation owing to the presence of single or multiple
      inhomogeneous regions in the object. This variation in the measured intensity is
      made use of to reconstruct regions of the inhomogeneous inclusions. In addition,
      it is possible to select a set of data from the above which is most likely least
      affected by the presence of the inhomogeneity, and estimate reasonably accurately
      the background optical properties from it. The reconstructed region is found to
      always contain the inhomogeneity and is of size approximately 140% by area of the
      inhomogeneity. With the regions to be reconstructed a priori known, a model-based
      iterative reconstruction procedure for reconstructing the optical properties of
      the region converged five times faster than without such information. It is also
      shown that whereas for the full object, a view-based propagation-backpropagation
      reconstruction procedure failed to converge, owing to large underdeterminacy of
      the problem, a smaller problem attempting to reconstruct a priori specified
      regions of interest converged and did so faster than a non-view-based approach
      for similar objects. Reconstruction results are presented from simulated
      transmitted intensity data from the following objects with regions of
      inhomogeneity in both absorption and scattering: (i) single centrally located
      inhomogeneity, (ii) two off-centred inhomogeneous regions of equal size and
      contrast (iii) two off-centred inhomogeneous regions of unequal size and equal
      contrast and (iv) two off-centred inhomogeneous regions of unequal size and
      contrast. Whereas the model-based iterative image reconstruction procedure gave
      good convergence in the first, second and third cases, in the fourth case the
      reconstructions failed to recover the exact numerical value of the optical
      properties in the higher contrast region.

PMID- 15742943
TI  - Modelling the transport of ionizing radiation using the finite element method.
AB  - Radiation therapy treatment planning is based on the calculation of the absorbed
      dose in the patient domain. For exact dose calculations, the solution of three
      coupled Boltzmann transport equations (BTEs) is needed to cover the transport of
      photons, electrons and positrons. In many situations, however, two coupled
      systems for photons and electrons are enough. The use of numerical methods in
      finding the exact solution of the unknown particle fluxes is necessary. In the
      stationary case, the BTE has six variables, three spatial, two directional and
      one energy variable. In this paper, we describe an approach in which the finite
      element method (FEM) is used to solve the six-dimensional problem. For the
      coupled photon-electron system, the variational formulation and the existence and
      uniqueness of the solution are derived. We simulate the solution of two coupled
      BTEs describing the travelling of photons and electrons in two spatial
      dimensions. The results are compared to Monte Carlo calculations with good
      agreement.

PMID- 15742944
TI  - Biological weighted effective dose in 205 MeV clinical proton beam.
AB  - The contribution of high linear energy transfer (L) charged particles to
      dosimetric and microdosimetric characteristics in a clinical proton beam was
      experimentally studied using an ionization chamber and track etched detectors.
      The particles mentioned are produced by proton nuclear interactions; at the Bragg
      peak region slowed down protons also contribute in the L region above several keV
      microm(-1). Due to these particles the biological weighted effective dose (BWED)
      of the beam changes with depth. The spectra of particles with L above 7 keV
      microm(-1) were established by means of track etched detectors, which permitted
      us to determine their contribution to dosimetric and microdosimetric
      characteristics of clinical proton beams. The studies were realized in the
      clinical proton beam of the JINR Dubna Phasotron, with a primary energy of 205
      MeV. The relative contribution to the absorbed dose of the particles with L above
      7 keV microm(-1) increases from several per cent at the beam entrance to several
      tens of per cent at the Bragg peak region. The relative biological weighted
      efficiency (RBWE) for radiotherapy has been calculated using a biological
      weighting function. It increases with depth from 1.02 at the beam entrance to
      about 1.25 at the Bragg peak region.

PMID- 15742945
TI  - Application of commercial MOSFET detectors for in vivo dosimetry in the
      therapeutic x-ray range from 80 kV to 250 kV.
AB  - The purpose of this study was to investigate the dosimetric characteristics
      (energy dependence, linearity, fading, reproducibility, etc) of MOSFET detectors
      for in vivo dosimetry in the kV x-ray range. The experience of MOSFET in vivo
      dosimetry in a pre-clinical study using the Alderson phantom and in clinical
      practice is also reported. All measurements were performed with a Gulmay D3300 kV
      unit and TN-502RDI MOSFET detectors. For the determination of correction factors
      different solid phantoms and a calibrated Farmer-type chamber were used. The
      MOSFET signal was linear with applied dose in the range from 0.2 to 2 Gy for all
      energies. Due to fading it is recommended to read the MOSFET signal during the
      first 15 min after irradiation. For long time intervals between irradiation and
      readout the fading can vary largely with the detector. The temperature dependence
      of the detector signal was small (0.3% degrees C(-1)) in the temperature range
      between 22 and 40 degrees C. The variation of the measuring signal with beam
      incidence amounts to +/-5% and should be considered in clinical applications.
      Finally, for entrance dose measurements energy-dependent calibration factors,
      correction factors for field size and irradiated cable length were applied. The
      overall accuracy, for all measurements, was dominated by reproducibility as a
      function of applied dose. During the pre-clinical in vivo study, the agreement
      between MOSFET and TLD measurements was well within 3%. The results of MOSFET
      measurements, to determine the dosimetric characteristics as well as clinical
      applications, showed that MOSFET detectors are suitable for in vivo dosimetry in
      the kV range. However, some energy-dependent dosimetry effects need to be
      considered and corrected for. Due to reproducibility effects at low dose levels
      accurate in vivo measurements are only possible if the applied dose is equal to
      or larger than 2 Gy.

PMID- 15742946
TI  - Cell detection in phase-contrast images used for alpha-particle track-etch
      dosimetry: a semi-automated approach.
AB  - A novel alpha-particle irradiator has recently been developed that provides the
      ability to characterize cell response. The irradiator is comprised of a
      collimated, planar alpha-particle source which, from below, irradiates cells
      cultured on a track-etch material. Cells are imaged using phase-contrast
      microscopy before and following irradiation to obtain geometric information and
      survival rates; these can be used with data from alpha-particle track images to
      assess cell response. A key step in this process is determining cell location
      within the pre-irradiation images. Although this can be done completely by a
      human observer, the number of images requiring analysis makes the process time
      consuming and tedious. To reduce the potential human error and decrease user
      interaction time, a semi-automated, computer-aided method of cell detection has
      been developed. The method employs a two-level adaptive thresholding technique to
      obtain size and position information about potential cell cytoplasms and nuclei.
      Proximity and geometry-based thresholds are then used to mark structures as
      cells. False-positive detections from the automated algorithm are due mostly to
      imperfections in the track-etch background, camera effects and cellular residue.
      To correct for these, a human observer reviews all detected structures,
      discarding false positives. When analysing two randomly selected cell dish image
      databases, the semi-automated method detected 92-94% of all cells and 94-97% of
      cells with a well-defined cytoplasm and nucleus while reducing human workload by
      32-83%.

PMID- 15742947
TI  - Real-time verification of HDR brachytherapy source location: implementation of
      detector redundancy.
AB  - Independent treatment verification for high dose rate (HDR) brachytherapy is
      needed to ensure that the treatment proceeds as prescribed. In this paper, we
      investigate the feasibility of a proposed real-time source position verification
      process. This process provides immediate confirmation of the source position
      during the treatment, so that the treatment can be aborted and modified if
      necessary. We show that an array of dosimeters placed on the patient's skin can
      independently verify the position in three dimensions. This verification was
      demonstrated by using a diamond detector placed in several locations on the
      surface of an anthropomorphic phantom. A mathematical algorithm was constructed
      to estimate the location of the source given a measured data set in the presence
      of tissue heterogeneity. The accuracy of the source localization was found to
      increase with the number of detectors used to compute the estimation of the
      source position. The resolution to which the 12 detectors can identify the
      location of the source was within 3 mm.

PMID- 15742948
TI  - Unified description and validation of Monte Carlo simulators in PET.
AB  - Several Monte Carlo simulators are currently available for positron emission
      tomography (PET). Because each code has been described in a different way, it is
      difficult to know which one is best suited to a specific application. To help
      clarify the capabilities and accuracy of different codes dedicated to PET
      simulations, we propose a uniform description of the code features. This
      description specifies features pertaining to the models used for simulating the
      physics of PET and for describing a PET acquisition, to the acceleration
      strategies and to the technical characteristics of the code implementation. To
      assess the code accuracy, we suggest validation procedures based on NEMA phantoms
      involving standard physical parameters and simulation of a complex activity
      distribution. A test characterizing the statistical properties of detected
      coincidences is also described. The proposed code description and validation
      procedures are illustrated by considering the SimSET and PET-EGS codes. These
      codes differ in many features, including models for randoms and dead time, and
      source description. Despite these differences, both codes yielded data with
      properties close to those of real data. Depending on the intended application,
      one code might be preferred however. Indeed, only PET-EGS allows for accurate
      modelling of count rates while SimSET is more computationally efficient. The
      proposed code description and validation procedures might help determine which
      code is most appropriate for a specific application.

PMID- 15742949
TI  - FDTD simulation of exposure of biological material to electromagnetic nanopulses.
AB  - Ultra-wideband (UWB) electromagnetic pulses of nanosecond duration, or
      nanopulses, are of considerable interest to the communications industry and are
      being explored for various applications in biotechnology and medicine. The
      propagation of a nanopulse through biological matter has been computed using the
      finite difference-time domain (FDTD) method. The approach required the
      reparametrization of existing Cole-Cole model-based descriptions of dielectric
      properties of biological matter in terms of the Debye model without loss of
      accuracy. Several tissue types have been considered. Results show that the
      electromagnetic field inside biological tissue depends on incident pulse rise
      time and width. Rise time dominates pulse behaviour inside tissue as conductivity
      increases. It has also been found that the amount of energy deposited by 20 kV m(
      1) nanopulses is insufficient to change the temperature of the exposed material
      for pulse repetition rates of 1 MHz or less, consistent with recent experimental
      results.

PMID- 15742950
TI  - Spectral characterization of local magnetic field inhomogeneities.
AB  - The purpose of this study was the characterization of local magnetic
      susceptibility deviations by spectral analysis of their induced magnetic field
      inhomogeneities. Magnetic resonance spectra and related signal decay curves of
      local susceptibility deviations were simulated for different volume fractions and
      compositions of the object within the VOI. The size or composition of the object
      was varied at constant volume fraction, constant object size, or at constant
      'magnetic strength' (defined as the product of the volume and the volume
      susceptibility of the object). Experimental spectra were acquired for individual
      metal spherical particles and a spherical air cavity. Where possible, spectra
      were used to characterize objects in terms of volume and composition. By
      simulations, a numerical relation was determined between the spectral broadening
      and the object's volume and composition. Comparison of spectra for various
      spherical objects showed the possibility of characterization with respect to size
      and composition. Experimental results confirmed the numerical results to a large
      extent, although the characterization was compromised by background signal decay,
      low volume fractions and limitations in signal-to-noise. In conclusion, spectral
      description of the field inhomogeneities related to small objects allows
      characterization of such objects with respect to size and composition. Practical
      applicability of the simulation results depends on background signal decay and
      volume fraction of the object.

PMID- 15742951
TI  - Calculation of magnetic field-induced current densities for humans from EAS
      countertop activation/deactivation devices that use ferromagnetic cores.
AB  - Compliance testing of electronic article surveillance (EAS) devices requires that
      induced current densities in central nervous system (CNS) tissues, i.e. brain and
      the spinal cord, be less than the prescribed safety limits. Even though
      ferromagnetic cores are mostly used for activation/deactivation of embedded
      magnetic tags, assumed equivalent air-core coils with guessed increased number of
      ampere turns have always been used to calculate the magnetic fields for the
      proximal region to which a customer is exposed. We show that at low frequencies
      up to several kilohertz, duality of electric and magnetic circuits may be
      exploited such that the shaped high reluctance core is modelled as though it was
      a higher conductivity electric circuit of the corresponding shape. The proposed
      procedure is tested by examples of two magnetic cores typical of countertop
      activation/deactivation devices. The equivalent exposure magnetic fields obtained
      from the dual electric fields are shown to be in excellent agreement (within +/
      5%) with those measured for these ferromagnetic EAS devices. The previously
      proposed impedance method is then used to calculate the induced current densities
      for a 1.974 x 1.974 x 2.93 mm resolution anatomic model of a human. For the two
      considered EAS systems using excitation currents of 5000 A turns at 200 Hz, the
      maximum 1 cm2 area-averaged induced current densities in the CNS tissues are
      calculated and found to be less than the ICNIRP safety limits.

PMID- 15742952
TI  - Radial and temporal variations in surface heat transfer during cryogen spray
      cooling.
AB  - Cryogen spray cooling (CSC) is a heat extraction process that protects the
      epidermis from thermal damage during dermatologic laser surgery. The objective of
      the present work is to investigate radial and temporal variations in the heat
      transferred through the surface of a skin phantom during CSC. A fast-response
      thermal sensor is used to measure surface temperatures every 1 mm across a 16 mm
      diameter of the sprayed surface of the phantom. An analytical expression based on
      Fourier's law and Duhamel's theorem is used to compute surface heat fluxes from
      temperature measurements. Results show that radial and temporal variations of the
      boundary conditions have a strong influence on the homogeneity of heat extraction
      from the skin phantom. However, there is a subregion of uniform cooling whose
      size is time dependent. It is also observed that the surface heat flux undergoes
      a marked dynamic variation, with a maximum heat flux occurring at the centre of
      the sprayed surface early in the spurt followed by a quick decrease. The study
      shows that radial and temporal variations of boundary conditions must be taken
      into account and ideally controlled to guarantee uniform protection during CSC of
      human skin.

PMID- 15742953
TI  - Reduction of Salmonella enterica serovar enteritidis colonization and invasion by
      an alfalfa diet during molt in Leghorn hens.
AB  - The standard method for molting to stimulate multiple egg-laying cycles in laying
      hens is feed deprivation. However, the physiological changes within hens caused
      by feed deprivation increase susceptibility of the hens to Salmonella enterica
      serovar Enteritidis (SE) infection. In an effort to develop an alternative method
      to induce molting without increasing susceptibility to SE, an alfalfa diet was
      compared with the standard molting method for the level of ovary regression and
      SE colonization. Hens over 50 wk of age were divided into 3 treatment groups (12
      hens/group): nonmolting by normal feeding (NM), molting by feed deprivation (M),
      and molting by alfalfa diet (A). Individual hens on all treatments were
      challenged orally with 10(5) cfu of SE on the fourth day after feed changes and
      were analyzed for ovary weight and SE colonization or invasion in crop contents,
      cecal contents, liver, spleen, and ovary on the ninth day. In 3 of the 4 trials,
      there was a significant decrease in SE colonization of the crop between the
      alfalfa diet (A) and the feed deprived molt (M). In most of the 4 trials, there
      was a significant reduction in SE infected organs in birds fed the alfalfa diet
      (A) compared with birds undergoing feed deprived molt (M). Most of the trials
      showed no significant difference in overall SE between A and NM. Therefore, the
      results of this study suggest that an alfalfa diet has the potential to be used
      as an alternative method for forced molting, without increasing the incidence of
      SE in eggs and internal organs.

PMID- 15742954
TI  - Do low-density diets improve broiler breeder welfare during rearing and laying?
AB  - Low-density diets may improve welfare of restricted fed broiler breeders by
      increasing feed intake time with less frustration of feed intake behavior as a
      result. Moreover, low-density diets may promote satiety through a more filled
      gastrointestinal tract, and thus feelings of hunger may be reduced. Broiler
      breeders were fed 4 different diets during the rearing and laying periods.
      Behavioral and physiological parameters were measured at different ages as
      indicators of hunger and frustration of the feeding motivation. A diet of 8.4
      MJ/kg as compared with a standard diet of 10.9 MJ/kg extended feeding time and
      reduced stereotypic object pecking at 6 and 10 wk of age. Furthermore,
      compensatory feed intake at 12 wk of age was reduced. During lay, differences in
      behavior were observed between the treatments that could be attributed to
      differences in feeding time. However, birds fed the diet with the lowest energy
      content (i.e., 9.2 MJ/kg) had higher heterophil to lymphocyte ratios (H/L) at 40
      wk of age compared with the other treatments, indicating that they experienced
      more stress during the laying period than the other treatments. This result could
      have been due to the very long feeding time of this treatment group during lay,
      which may be stressful. In conclusion, a low-density diet of 8.4 MJ/kg may reduce
      hunger and frustration in the first half of the rearing period. However, for
      substantial improvement of broiler breeder welfare during rearing, more extreme
      diet modifications are required.

PMID- 15742956
TI  - Insulin-like growth factor-I gene polymorphism associations with growth, body
      composition, skeleton integrity, and metabolic traits in chickens.
AB  - Molecular genetic selection on individual genes is a promising method to
      genetically improve economically important traits in chickens. A resource
      population was developed to study the genetics of growth, body composition,
      skeletal integrity, and metabolism traits. Broiler sires were crossed to dams of
      2 diverse, highly inbred lines (Leghorn and Fayoumi), and the F1 birds were
      intermated by dam line to produce broiler-Leghorn and broiler-Fayoumi F2
      offspring. Growth, body composition, skeletal integrity, and hormonal and
      metabolic factors were measured in 713 F2 individuals. Insulin-like growth factor
      I (IGF1) was selected for study as a biological and positional candidate gene. A
      single nucleotide polymorphism (SNP) was identified between the founder lines in
      the IGF1 promoter region, and a PCR-RFLP assay was developed. A mixed model was
      used to statistically analyze associations of IGF1-SNP1 with phenotypic traits.
      The IGF1-SNP1 had significant associations with most recorded traits, except
      metabolic traits. Strong interactions between the IGF1 gene and genetic
      background on growth traits in the 2 F2 populations suggest that genetic
      interaction is an important aspect for consideration before using the IGF1-SNP1
      in marker-assisted selection programs. Several beneficial effects (improved
      growth, increased breast muscle weight, decreased abdominal fat, and enhanced
      skeletal integrity) associated with 1 allele indicate the presence of 1 or more
      loci near IGF1-SNP1 controlling biologically diverse and economically important
      traits in chickens.

PMID- 15742955
TI  - Effects of drinking water treatment on susceptibility of laying hens to
      Salmonella enteritidis during forced molt.
AB  - Feed deprivation is used in the layer industry to induce molting and stimulate
      multiple egg-laying cycles in laying hens. Unfortunately, the stress involved
      increases susceptibility to Salmonella enteritidis (SE), the risk of SE-positive
      eggs, and incidence of SE in internal organs. Leghorn hens over 50 wk of age were
      divided into 4 treatment groups of 12 hens each in experiment 1 and 3 treatment
      groups of 12 hens in experiments 2 and 3; hens were placed in individual laying
      hen cages. Treatment groups were 1) nonmolted (NM) and received feed and
      distilled water for 9 d, 2) force molted by feed removal for 9 d and received
      distilled water, 3) force molted by feed removal for 9 d and received 0.5% lactic
      acid (LA) in distilled water. An additional group (4) in experiment 1 only was
      force molted by feed removal for 9 d and received 0.5% acetic acid in distilled
      water. Seven days before feed removal hens were exposed to an 8L:16D photoperiod,
      which was continued throughout the experiment. Individual hens among all
      treatments were challenged orally with 10(4) SE on d 4 of feed removal. When
      compared with the NM treatments, weight losses were significantly higher in the M
      treatments, regardless of water treatments. When compared with NM treatments,
      crop pH was significantly higher in the M treatment receiving distilled water.
      Crop pH was reduced to that of the NM controls by 0.5% acetic acid in the
      drinking water. No consistent significant changes were observed for volatile
      fatty acids. The number of hens positive for SE in crop and ceca after culture
      and the number of SE per crop and per gram of cecal contents were higher in the M
      treatments, when compared with the NM treatments, but there was no effect of
      addition of either of the acids to the drinking water. Additional research using
      different acid treatment regimens may provide a tool for reducing the incidence
      of SE in eggs and internal organs during and following molting of laying hens.

PMID- 15742957
TI  - Directional selection for specific sheep cell antibody responses affects natural
      rabbit agglutinins of chickens.
AB  - Agglutination data from generations 8 through 19 indicate that bidirectional
      selection for specific SRBC antibody responses was successful in a line cross of
      ISA x Warren medium heavy layers. After 11 generations titers of the high SRBC
      selected line (H line) were nearly 1:32,000; those of the low SRBC selected line
      (L line) were less than 1:2, but titers of the randombred control line remained
      stable at 1:32. Directional SRBC selection also affected levels of a naturally
      occurring rabbit cell agglutinating antibody (RRBC), presumably the avian form of
      alpha-galactose antibody (anti-Gal). This indirect response was biphasic and
      opposite in direction to the SRBC responses through generation 14 after which
      anti-Gal titers of all 3 lines increased. At generation 19, line H had the
      highest agglutinin titers; of both types, control line was intermediate, and line
      L was lowest. The correlation between SRBC and RRBC titers was 0.43 (P = 0.0).
      Females had higher titers than males, but the difference was only significant for
      the SRBC antibody (P = 0.028). Qualitative changes in anti-Gal accompanied SRBC
      selection. Rabbit agglutinins of 4 types were recognizable: classic, granular,
      annular, and one negative or very weak reaction. The score type means in line L
      were highest, in the control line were intermediate, and in line H were lowest,
      suggesting avidity differences now exist among these lines. The results show
      integration of natural and acquired immune systems because selection for one
      temporarily affected the other. Given the importance of anti-Gal in primates, our
      results should stimulate further study of this antibody in poultry species.

PMID- 15742958
TI  - Dietary tryptophan need of broiler males from forty-two to fifty-six days of age.
AB  - Tryptophan requirements of broiler males from 42 to 56 d of age were studied.
      Ross x Ross 308 chicks were placed in an open-sided house, and provided common
      starter and grower diets from 0 to 42 d of age. Subsequently, a corn, soybean
      meal, corn gluten meal, and gelatin combination of feedstuffs provided 0.12% Trp
      to which 0.04% increments of L-Trp were supplemented at the expense of an
      isonitrogenous amount of L-Glu to 0.24%. Birds that received diets containing
      0.12% Trp exhibited aberrant behavior based on the spillage of considerable
      amounts of feed from the trough and contamination of adjacent waterers with floor
      litter. There were reductions in body weight gain, feed conversion, and carcass
      and breast fillets weights and yields with dietary Trp at 0.12%, but these were
      not affected at Trp levels at or above 0.16%. Exponential regression analyses
      showed that body weight gain improved as Trp increased, with maximum overall
      performance being attained at 0.17%, whereas chilled carcass weight maximized at
      0.16% dietary Trp. Nitrogen retention measured using the same experimental feeds
      and sample birds at 48 to 49 d of age was unaffected by dietary Trp. Plasma uric
      acid, albumin, total protein, and aspartate-transferase measured concurrently
      with nitrogen retention were not altered; however, blood glucose was reduced in
      broilers fed 0.12% dietary Trp. Overall results suggest that broiler males need
      approximately 0.17% dietary Trp between 42 and 56 d of age, which closely agrees
      with the NRC (1994) recommendation of 0.16% Trp estimated from modeling for this
      feeding period.

PMID- 15742959
TI  - Effect of inorganic versus organic selenium on hen production and egg selenium
      concentration.
AB  - A 28-d experiment using 288 Hy-Line W-36 laying hens was conducted to compare
      sodium selenite (SS) with Se-enriched yeast (SY). The Se from SS or SY was
      supplemented into a corn-soybean meal basal diet at 0, 0.15, 0.30, 0.60, or 3.00
      ppm, and the basal diet was formulated to provide 0.82% lysine and 2,950 kcal/kg
      of ME. Each treatment was replicated 4 times with 2 cages of 4 hens per cage in
      each replicate. Hen production was assessed daily, and 2 eggs per replicate were
      collected every 4 d for whole-egg Se analysis. Albumen quality was assessed at 2
      egg storage temperatures (7.2 vs. 22.2 degrees C) with the eggs collected on d 24
      and 28, respectively. The percentage of dirty and cracked eggs was greater (P <
      0.04) in hens fed SY than in those fed SS. Percentage hen-day production was not
      affected (P > 0.05) by diet. Albumen quality of eggs stored at 22.2 degrees C was
      improved (P < 0.04) in eggs from hens fed SS, but there was no difference (P >
      0.05) in albumen quality of eggs stored at 7.2 degrees C. Egg weight was linearly
      increased (P < 0.01) by SY. Whole-egg Se levels were linearly increased (P <
      0.01) as dietary Se level increased for both sources of Se, but eggs from hens
      fed SY had higher (P < 0.01) Se concentrations than those fed SS. The results
      from this experiment indicate that percentage hen-day production is not affected
      by Se source, and that SY increases egg Se concentrations more than SS.

PMID- 15742960
TI  - Performance and nutrient retention responses of broilers to dietary oxyhalogenic
      and ionic salts.
AB  - Two experiments were conducted to determine the effects of 2 ionic and
      antimicrobial mixtures on broiler performance and nutrient retention. In
      experiment 1, male broilers were fed 6 diets in a 2 x 3 factorial experiment (5
      cages/diet, 9 chicks/cage) from 0 to 21d of age. Diets with 2 nutrient densities
      [normal industry diet (ND) and a low nutrient density diet (82% of ND)] and 3
      ionic and antimicrobial mixtures [none (control) or 1 of 2 formulations
      containing different mixtures of ionic salts and oxyhalogenic compounds (sodium
      salts of chlorite, chlorate, chloride, borate, sulfate, bromide, salicylate, and
      hydrogen peroxide) at 4.4 mL/kg of feed (mix A and B)]. Birds fed mix B (568.6 g)
      were heavier (P < 0.05) at 21d of age than birds fed the control diet (501.7 g)
      and BW of birds fed mix A (536.1 g) did not differ from mix B or controls.
      Phosphorus and nitrogen retention from 18 to 20 d in birds fed mix B (78.05% and
      82.23%, respectively) was greater (P < 0.05) than birds fed mix A (60.21 and
      71.22%, respectively) and birds fed mix A had greater (P < 0.05) retention than
      birds fed the control diet (45.94 and 69.06%, respectively). In experiment 2,
      chicks were fed either 4.4 mL of mix B/kg feed, a diet with salinomycin and
      bacitracin, or a control diet. Birds fed the control or mix B diet had greater (P
      < 0.05) BW at 18 d than birds on the antibiotic treatment, whereas diet or
      nutrient retention differences were not present at 42 d of age. In conclusion,
      the ionic and antimicrobial mixtures improved performance and nutrient retention
      in young broilers but these did not last until market age.

PMID- 15742961
TI  - Efficacy of an evolved Escherichia coli phytase in diets of broiler chicks.
AB  - An evolved Escherichia coli-derived phytase was evaluated for its efficacy in
      improving growth performance and nutrient utilization of broiler chicks. One
      hundred forty-four 7-d-old male broiler chicks were grouped by weight into 6
      blocks of 6 cages with 4 birds per cage. Six corn-soybean meal-based mash diets
      were randomly assigned to cages within each block. The 6 diets were adequate P
      (7.7 g of P/kg of diet), low P (3.9 g of P/kg of diet), low P diet plus 0.75 or
      1.5 g of inorganic P from monosodium phosphate, and low P diet plus the evolved
      Escherichia coli phytase at 500 or 1,000 units/kg of diet. The chicks were fed
      the experimental diets from 8 to 22 d of age. The evolved Escherichia coli
      phytase improved weight gain (P < 0.05), feed intake (P < 0.01), percentage tibia
      ash (P < 0.01), and retention of P (P < 0.001), Ca (P < 0.01), N (P < 0.05), and
      a number of amino acids (P < 0.05). The evolved Escherichia coli phytase was,
      therefore, efficacious in improving broiler growth performance, bone
      characteristics, and retention of P, Ca, N, and a number of amino acids.

PMID- 15742962
TI  - Evaluation of alternative nonlinear mixed effects models of duck growth.
AB  - Two nonlinear growth functions were evaluated on 6 groups of 32 ducks. Ducks were
      randomly assigned to 1 of 6 dietary treatments and weighed weekly from 1 to 43 d
      of age. The Weibull function had the form: BW(it) = A - (A - B) exp - [(C - 1)/C]
      (t/IP)**C, where BW(it) is the BW of the ith duck at age t in days and A, B, C,
      and IP are fixed parameters. The variable A represents mature BW and the variable
      IP is the age (inflection point) at which maximum average daily gain is achieved.
      The addition of a single random effect to the Weibull growth function (ip), in
      which the age to reach the BW at the overall population inflection point of each
      duck varies, provided a substantially better fit than any other alternative fixed
      or mixed models. Overall, the Weibull function under-predicted the d-1 BW (46.7
      vs. 55.1 g, P < 0.05) and over-predicted the d-8 BW (233.6 vs. 211.7 g, P <
      0.05). The predicted BW from d 15 to 43 was very close to the actual mean BW at
      each age. This model predicts that the between-duck variance in BW increases with
      age and that the CV increases from 1 to 8 d of age, reaches a plateau from 15 to
      22 d of age, and then slowly declines. This mixed effects model predicts the mean
      age and approximate variation in age that ducks require to reach a specific BW,
      and is easily adaptable to stochastic modeling.

PMID- 15742963
TI  - A comparison of two sources of phytase in liquid and dry forms in broilers.
AB  - Research with corn-soybean meal diets was conducted to compare phytase sources in
      commercial broilers. A Ca to nonphytate P (nPP) ratio of 2.5:1 was maintained in
      all diets. Experiments 1 and 2 were conducted from d 4 to 13 (experiment 1) or d
      9 to 23 post-hatching (experiment 2) in batteries. The 10 treatments used in both
      experiment were: Diets 1 to 4 = 0.20, 0.25, 0.30, or 0.35% nPP; Diets 5 to 7 =
      diet 1 plus 100, 200, or 300 phytase units/kg of diet from Natuphos (NAT); and
      Diets 8 to 10 = diet 1 plus 100, 200, or 300 phytase units/ kg of diet from
      Ronozyme (RON). As nPP levels increased, daily gain (ADG), feed intake (ADFI),
      gain:feed, and toe and tibia ash percentage were linearly increased (P < 0.06) in
      experiments 1 and 2. Incremental addition of phytase, regardless of source,
      linearly increased (P < 0.07) ADG and ADFI in experiment 1. Broilers fed NAT had
      higher (P < 0.07) toe ash percentage in experiment 1 and 2, and higher (P < 0.02)
      ADG and ADFI in experiment 2 than those fed RON. In experiment 3, 3,360 broilers
      were used to test 2 dry phytase products from 0 to 41 d posthatching in a 3-phase
      feeding program. The treatments were: Diet 1) adequate Ca and nPP; Diet 2) nPP
      reduced by 0.20%; Diets 3 to 5 = diet 2 plus 300, 500, or 750 phytase units/kg of
      diet from NAT; and Diets 6 to 8 = Diet 2 plus 300, 500, or 750 phytase units/kg
      of diet from RON. Broilers fed the adequate Ca and nPP diet had improved ADG and
      ADFI overall, and tibia ash weight and percentage in all growth phases (P < 0.03)
      compared with those fed the reduced Ca and nPP diets. Overall, ADG and ADFI were
      linearly increased (P < 0.05) by incremental phytase addition in experiment 3.
      Both NAT and RON produce similar growth and bone ash traits in commercial
      broilers.

PMID- 15742964
TI  - Growth responses to dietary energy and lysine at high and low ambient temperature
      in male turkeys.
AB  - The effects of ambient temperature (T; 18 vs. 28 degrees C), dietary energy level
      [E; 90, 100, and 110% of NRC (1994) recommendations], and dietary lysine level
      [LYS; 105 vs. 120% of NRC (1994) recommendations], and their interactions on feed
      intake, BW gain, feed:gain ratio, and carcass yields of male turkeys were studied
      from 29 to 140 d of age. The experiment was designed as a split plot, including T
      as the main plot and E and LYS as the subplot, with 60 pens containing 10 male
      turkeys each. Overall, feed intake, BW gain, and feed:gain ratio were
      significantly lower at high compared with low T. Feed intake decreased linearly
      as E increased and was more pronounced at low compared with high T. Metabolizable
      energy intake increased more at high compared with low T as E increased. Turkeys
      that were fed the highest E gained less weight until 84 d of age than those fed
      the lowest E. Dietary lysine was not the limiting amino acid because birds showed
      no response to extra lysine. Feed:gain decreased linearly as E level increased.
      Until 84 d of age, feed:gain decreased more at low compared with high T as E
      level increased. Breast meat yields were lower, and thigh, drum, and wing yields
      were higher at high than at low T. The highest E resulted in lower cold carcass
      yields, and breast meat yields, and higher thigh and drum yields than the lowest
      E. Dietary lysine level did not affect carcass yield. The results imply that when
      dietary lysine levels are adequate, dietary energy may be increased above NRC
      (1994) to improve feed efficiency, but some of the limiting amino acids after
      lysine may be increased in high-density diets to optimize breast meat yield.
      Particularly at high temperature in the period after 16 wk of age, dietary energy
      contents may be increased to at least 110% of NRC (1994) because turkeys will
      need more energy to dissipate heat.

PMID- 15742965
TI  - Impact of glutamine and Oasis hatchling supplement on growth performance, small
      intestinal morphology, and immune response of broilers vaccinated and challenged
      with Eimeria maxima.
AB  - Seven hundred and twenty hatchling broilers were allotted to 12 treatment groups.
      Groups 1 and 2 were fasted for 48 h posthatch; groups 3 and 4 were fasted for 48
      h followed by ad libitum access to a 1% glutamine (Gln) diet; groups 5 and 6 had
      ad libitum access to a common diet; groups 7 and 8 had access to a 1% Gln diet
      posthatch; groups 9 and 10 were fed regular Oasis hatchling supplement; and
      groups 11 and 12 were fed Oasis sprayed with 1% Gln for the first 48 h posthatch.
      The birds in treatment groups 2, 4, 6, 8, 10, 11, and 12 were vaccinated with
      Eimeria maxima posthatch, and all birds were orally challenged with high dose E.
      maxima on d 22. During the first 2 wk, birds in group 7 had the highest gain and
      feed efficiency among treatments (P < 0.01). Compared with birds in the nonGln
      groups, birds in the Gln group had higher gain, feed efficiency, and livability
      (P < 0.05). Among the Fast (groups 1 to 4), Feed (groups 5 to 8), and Oasis
      (groups 9 to 12) groups, birds in the Feed groups had the highest gain during d 0
      to 21 (P < 0.01). During d 22 to 28, birds in the Fast groups had the lowest BW
      and livability (P < 0.01), and the nonvaccinated birds had lower gain and feed
      efficiency relative to vaccinated birds (P < 0.01). Birds in the Feed and Oasis
      groups had higher villus height (VH) of mid small intestine than Fast groups at d
      2 and 7 (P < 0.05), and nonvaccinated birds had higher VH than vaccinated birds
      (P < 0.01) at d 7 after hatch. On d 14, there were differences in serum
      interferon-gamma (P < 0.05) levels among treatments. During d 22 to 28,
      vaccinated birds had lower lesion scores in the mid small intestine than
      nonvaccinated birds (P < 0.01), and birds in the Feed or Oasis groups had lower
      lesion scores compared with the Fast groups (P < 0.02). These results indicated
      the importance of immediate access to feed posthatch, the beneficial effects of
      feeding Oasis hatching supplement and Gln after hatch, as well as the necessity
      of the vaccination program against coccidiosis challenge.

PMID- 15742966
TI  - The influence of dietary sodium chloride, arginine:lysine ratio, and methionine
      source on apparent ileal digestibility of arginine and lysine in acutely heat
      stressed broilers.
AB  - The present study was carried out to determine the ileal digestibility of Arg and
      Lys in acutely heat-stressed broilers using diets varying in Arg:Lys ratio, NaCl
      concentration, and Met Source. Male broilers were maintained at 22 degrees C from
      21 to 33 d of age and then at 32 degrees C from 33 to 38 d of age. From 28 to 38
      d of age, birds were fed a diet with an Arg:Lys ratio of 1.05 and 3 g of
      supplemental NaCl/kg of diet with or without L-arg free base to increase the
      Arg:Lys to 1.35, and with or without 3 g/kg of additional NaCl. Methionine was
      supplied as equimolar amounts of DL-Met or 2-hydroxy-4-(methylthio)-butanoic acid
      in a 2 x 2 x 2 design. At 38 d of age, digesta were collected from the terminal
      ileum, and amino acid analyses were conducted on feed and digesta samples and
      compared with acid-insoluble ash (dietary celite) to calculate the apparent ileal
      digestibilities of Lys and Arg. Increasing the NaCl concentration and the
      presence of HMB significantly decreased the digestibility of both Arg and Lys,
      whereas increasing the Arg:Lys ratio increased the digestibility of only Arg but
      did increase BW gain (P = 0.08). An interaction between dietary NaCl and Arg:Lys
      ratio as well as the 3-way interaction suggested that dietary NaCl could affect
      the apparent ileal digestibility of Arg and Lys at certain Arg:Lys ratios and the
      response may be influenced by the Met source.

PMID- 15742967
TI  - Feed allowance-genotype interactions in broiler breeder hens.
AB  - Ad libitum feeding reduces livability and reproductive fitness in broiler breeder
      hens. Two genotypes, a standard (S) and an experimental dwarf broiler breeder
      (E), were fed ad libitum (SA and EA, respectively), restricted at 55% of ad
      libitum feed intake (intermediate restriction) from 6 to 15 wk of age (SI and EI,
      respectively), or restricted (SR and ER, respectively) to match a standard growth
      curve with a diluted mash feed (2,400 kcal/kg). The experiment was repeated at 2
      locations (experiment 1 = 672 hens in pens from 0 to 40 wk; experiment 2 = 420
      hens in pens and cages from 0 to 53 wk). Feed restriction reduced adult BW by 20%
      compared with ad libitum feeding, delayed sexual maturity by 2 to 4 wk, and
      improved livability. Hens fed the intermediate diet immediately compensated after
      15 wk of age to reach BW, sexual maturity, and livability close to those of ad
      libitum-fed hens. The E genotype exhibited better tolerance to ad libitum feeding
      than the S genotype in all measured aspects. Average laying rate during the first
      24 wk of lay was 66.4, 77.4, 69.9, 47.2, 57.9, and 72.4% for EA, EI, ER, SA, SI,
      and SR respectively in experiment 2. Egg abnormalities (double yolk, shell
      problems) decreased after the peak of lay but remained consistently higher for S
      compared with E, and for ad libitum and intermediate diets compared with the
      restricted diet. Yolk deposition rate was measured by a double dye technique.
      Duration of yolk rapid growth was 8.8 d in E and 9.3 d in S hens (P < 0.001), but
      this difference did not explain the observed variations in laying rate. The
      potential to increase feed allowances even with a diluted diet in broiler breeder
      hens requires adapted genotypes.

PMID- 15742968
TI  - Superoxide radical production in chicken skeletal muscle induced by acute heat
      stress.
AB  - Heat stress is of major concern for poultry, especially in the hot regions of the
      world because of the resulting poor growth performance, immunosuppression, and
      high mortality. To assess superoxide (O2*-) production in mitochondria isolated
      from skeletal muscle of chickens (n = 4 to 8) exposed to acute heat stress,
      electron spin resonance (ESR) spectroscopy using 5,5-dimethyl-1-pyrroline N-oxide
      (DMPO) as a spin trap agent and lucigenin-derived chemiluminescence (LDCL) method
      were applied. ESR spectra of suspensions containing mitochondria from control and
      acute heat-treated meat-type chickens showed similar hyperfine coupling constants
      (aN = 1.44 mT, aHbeta = 0.12 mT, and aHbeta = 0.11 mT) to those of DMPO-O2*-
      adducts observed in a hypoxanthine-xanthine oxidase system. Heat exposure
      resulted in enhancement of the DMPO-O2*- signal. The results using LDCL showed
      significantly enhanced superoxide production in heat stress-treated skeletal
      muscle mitochondria of meat-type chickens, whereas no such increase was observed
      in laying chickens. The enhancement of superoxide production in the former case
      was associated with heat-induced increments in rectal and muscle temperatures,
      leading to significant body weight loss. In contrast, the latter case showed no
      increase in temperatures, although there was a slight decrease in body weight
      gain. Percentage increases of superoxide production in the presence of
      carboxyatractylate, a specific inhibitor of adenine nucleotide translocator
      (ANT), were the same for skeletal muscle mitochondria from meat- and laying-type
      chickens from the control or heat stress-treated group. This finding suggests the
      irrelevance of ANT in the regulation of reactive oxygen species flux under heat
      stress conditions. The study provides the first evidence of superoxide anion
      production in the skeletal muscle mitochondria of meat-type chickens in response
      to acute heat stress.

PMID- 15742969
TI  - Effects of turning duration during incubation on embryo growth, utilization of
      albumen, and stress regulation.
AB  - Eggs from Cobb broiler breeders were incubated for 18 d. Eggs were not turned
      (T0) or were turned until 9 (T9), 12 (T12), 15 (T15), or 18 (T18) d. First, the
      effects of turning on embryo and albumen weights were studied. Samples of eggs
      were opened at d 9, 12, 15, and 18 for embryo and albumen weighing. The results
      show that embryos from unturned eggs had lower weights and higher remaining
      albumen weights than those from turned eggs. At d 18, albumen utilization was
      completed in the T12, T15, and T18 groups only. Also, further turning until d 15
      and 18 increased embryo weights. The responsiveness of the embryo after
      adrenocorticotropic hormone (ACTH) injection was studied to test stress control
      in embryos. Blood samples were collected from embryos at 60 and 150 min after
      injection at d 12, 15, and 18 and were analyzed for corticosterone
      concentrations. The results showed that basal corticosterone levels increased
      with embryo age. At 60 min after ACTH injection, corticosterone levels were lower
      at d 12 than at d 15 and 18. At 150 min after ACTH injection, corticosterone
      levels followed different trends according to incubation stage and turning
      duration. The highest basal corticosterone levels were obtained with the T15
      group at d 15 and 18. Also at d 18, corticosterone levels in the T15 group were
      the highest at 150 min after ACTH injection. We concluded that egg turning was
      required during incubation until d 12, at least, and should not be stopped until
      after d 15.

PMID- 15742970
TI  - Changes in egg production rate induced by progesterone injection in broiler
      breeder hens.
AB  - A polycystic ovarian follicle (PCOF) syndrome associated with high baseline
      concentrations of progesterone (P4) without preovulatory luteinizing hormone (LH)
      surges has been reported in turkey hens. The PCOF syndrome could be induced in
      turkey hens by injecting P4 (0.33 mg/kg per d) daily early in the reproductive
      period for 10 to 12 d and then waiting 3 wk for the syndrome to develop. It was
      hypothesized that an arrest in laying associated with the PCOF syndrome could be
      induced by daily injection of P4 in restricted-fed broiler breeder hens. Hens
      were divided into 5 treatment groups and were injected subcutaneously daily with
      P4 in canola oil at dosages of 0, 0.17, 0.33, 0.5, and 1.5 mg/kg per d for 13 d,
      at 14 wk of egg production when they were 41 wk of age. Blood samples were
      collected on d 7 and 13 immediately before P4 injection. Oviductal and ovarian
      morphologies were measured at necropsy 1 d after the last P4 injection. Egg
      production rate was reduced by injection of P4 at dosages < 0.17 mg/kg per d. At
      dosages of 0.5 and 1.5 mg/kg per d, ovarian hierarchical follicles had regressed.
      None of the broiler breeder hens had the PCOF syndrome at necropsy, but a high
      incidence of hens holding hard-shelled uterine eggs for several days was
      observed. Concentrations of LH decreased with P4 injection at > 0.17 mg/kg per d,
      and P4 concentrations were increased with P4 injection at > 0.5 mg/kg per d.
      Estradiol-17beta (E2) concentrations were decreased at all P4 dosages. It was
      concluded that egg production rate was reduced by daily injection of P4 at
      dosages > 0.17 mg/kg per d, and egg production ceased and ovarian follicles and
      the oviduct regressed at dosages > 0.50 mg/kg per d. The PCOF syndrome, however,
      was not induced in restricted-fed broiler breeder hens by P4 injection.

PMID- 15742971
TI  - Microstructure and thermal characteristics of Thai indigenous and broiler chicken
      muscles.
AB  - The microstructure and thermal characteristics of Thai indigenous (Gallus
      domesticus) and broiler chicken (commercial line CP707) biceps femoris and
      pectoralis muscles were determined. Perimysium thicknesses were 14.2 microm for
      biceps femoris muscle and 7.10 microm for pectoralis muscle of indigenous chicken
      muscles, thicker than those of broiler muscles, which were 9.93 microm for biceps
      femoris muscle and 3.87 microm for pectoralis muscle (P < 0.05). Five endothermic
      peaks with peak transition temperatures (Tp) of 54.9, 61.7, 65.4, 70.6, and 76.1
      degrees C were obtained for broiler pectoralis muscle, whereas only 3 endothermic
      peaks (Tp of 56.6, 62.6, and 74.9 degrees C) were obtained for broiler biceps
      femoris muscle. Thai indigenous biceps femoris and pectoralis muscles had
      endothermic peaks with Tp ranges of 53.5 to 54.8, 60.7 to 61.9, and 75.9 to 76.9
      degrees C. The fiber diameters of Thai indigenous chicken muscles were greater (P
      < 0.05) than those of the broiler, 31.7 vs. 20.4 microm for biceps femoris muscle
      and 28.9 vs. 26.6 microm for pectoralis muscle, respectively. After cooking at 80
      degrees C for 10 min, the fiber diameter of indigenous chicken muscles
      significantly decreased while those of the broiler significantly increased. The
      mean of sarcomere lengths of the raw muscles ranged from 1.56 to 1.64 microm and
      decreased to 0.92 to 1.32 microm (P < 0.001) for broiler muscles and 1.22 to 1.35
      microm (P < 0.001) for indigenous chicken muscles after cooking. The perimysium
      and endomysium of broiler muscles melted after cooking at 80 degrees C, however,
      only slight disintegration was observed in these tissues in the indigenous
      chicken muscles.

PMID- 15742972
TI  - Effects of dietary metabolizable energy and crude protein concentrations on
      growth performance and carcass characteristics of French guinea broilers.
AB  - This study was undertaken to assess dietary CP and ME concentrations for optimum
      growth performance and carcass characteristics of French guinea broilers. In a 3
      x 3 factorial arrangement, 396 1-d-old French guinea keets were randomly assigned
      to experimental diets with 3,050, 3,100, and 3,150 kcal of ME/kg of diet; each
      contained 21, 23, and 25% CP, respectively, from 0 to 4 wk of age (WOA). From 5
      to 8 WOA, experimental diets had 3,100, 3,150, and 3,200 kcal of ME/kg of diet,
      and each contained 19, 21, and 23% CP, respectively. Each dietary treatment was
      replicated 3 times, and feed and water were provided ad libitum. Body weight and
      feed consumption were measured weekly, whereas carcass characteristics were
      evaluated at 8 WOA. For the most part, birds on 3,100 and 3,150 kcal of ME/kg of
      diet at 0 to 4 WOA exhibited greater (P < 0.05) BW gain, greater carcass and
      breast weights (P < 0.05), and lower (P < 0.05) feed consumption and feed
      conversion ratios (FCR) than those on a diet with 3,050 kcal of ME/kg. Mean feed
      consumption of birds fed 25% CP diets was higher (P < 0.05) than those on other
      dietary CP concentrations. Mean BW gain, FCR, and carcass and breast weights of
      birds fed 25 and 23% CP diets from 0 to 4 WOA were not different (P > 0.05), but
      they were better (P < 0.05) than those of birds on 21% CP diets. Positive
      correlations (P < 0.01) were noted between live weight and weight of carcass,
      breast, thigh, drumstick, and wing of guinea broilers. Thus, diets with 3,100
      kcal of ME/kg and 23% CP or with 3,150 kcal of ME/kg and 21% CP at 0 to 4 WOA and
      5 to 8 WOA, respectively, were used more efficiently by French guinea broilers.

PMID- 15742973
TI  - Descriptive sensory analysis of broiler breast fillets marinated in phosphate,
      salt, and acid solutions.
AB  - Sensory attributes of fully aged broiler breast fillets marinated in a 6% NaCl
      solution containing 2% sodium tripolyphosphate (2P), 2% citric acid (2C), 2%
      acetic acid (2A), 1% citric acid plus 1% phosphate solution (1C), or 1% acetic
      acid solution plus 1% phosphate (1A) were studied. A 6% NaCl (6S) solution with
      no additives was used as control. Oven-cooked samples (177C degrees oven; 75
      degrees C internal temperature) were evaluated by a 9-member trained descriptive
      analysis sensory panel that rated the intensities of 26 different flavor and
      texture attributes using 15-point line scales. Data were analyzed using general
      linear model SAS procedures to determine significant differences (P < or = 0.05)
      in individual sensory attributes due to marinade treatment. All sensory
      attributes were scored in the low intensity range (1.5 to 5.0). Brothy, vinegar,
      and residual particles were the only individual attributes rated significantly
      different (P < or = 0.05) due to treatment. Multivariate analyses indicated that
      all sensory attributes formed 2 dimensions that explained 57% of variation in the
      data. The low intensity values for texture attributes indicated possible negative
      consequences due to phosphates, salt, and acids when used with fully aged
      fillets.

PMID- 15742975
TI  - Oxidation and rearrangements of flavanones by mammalian cytochrome P450.
AB  - To clarify the metabolic pathways of flavanones in mammals, the metabolism of (+/
      )-flavanone and (+/-)-4'-methoxyflavanone by rat liver microsomes and recombinant
      human P450s in which structural changes are readily identifiable were examined.
      The beta-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent formation
      of flavone plus (+/-)-2,3-trans-flavanonol and of 4'-methoxyflavone plus (+/-)
      2,3-trans-4'-methoxyflavanonol, respectively, by rat liver microsomes was
      observed. The same metabolites were generated by recombinant human P450s in
      addition to the formation of isoflavone from (+/-)-flavanone. The kinetic isotope
      effects in these reactions were examined using deuterated (+/-)-flavanone and (+/
      )-4'-methoxyflavanone. There was a strong isotope effect in the production of
      flavanonols, but the isotope effect in the production of flavones was small. The
      results indicated that the P450-mediated conversion of (+/-)-flavanone and of (+/
      )-4'-methoxyflavanone to the corresponding metabolites proceeded via abstraction
      of a hydrogen radical from the C-2- or C-3-position of the flavanone skeleton.
      The antioxidant properties of flavanone and its metabolites were examined by
      measuring superoxide-scavenging activity in a xanthine-xanthine oxidase
      cytochrome c system. (+/-)-2,3-trans-Flavanonol had higher activity than that of
      other flavonoids. Flavanones are metabolized by mammalian P450s, providing
      important information relevant to the metabolism and pharmacological action of
      dietary flavanones.

PMID- 15742974
TI  - Different mechanisms of handling ingested polycyclic aromatic hydrocarbons in
      mammalian species: organ-specific response patterns of CYP1A1-induction after
      oral intake of PAH-contaminated soils.
AB  - Potential effects of xenobiotics on humans are largely derived from studies with
      animal models. However, due to species-specific processing of xenobiotics,
      susceptibilities to xenobiotic-dependent adverse effects are known to differ
      between species. We analysed the basal expression of cytochrome P450 (CYP)
      enzymes in several organs of minipigs and rats, and their inducibility upon oral
      intake of soils containing polycyclic aromatic hydrocarbons (PAH). CYP-specific
      enzymatic activities were determined in duodenum, liver and kidney microsomes.
      Upon ingestion of PAH-contaminated soils, CYP1A1 is differentially induced in a
      tissue-specific and dose-dependent manner in duodenum, liver and kidney of
      minipigs and rats. In the duodenum, the induction response is low in rats (about
      4-fold) but it is high in minipigs (8-230-fold). By contrast, induced hepatic
      CYP1A1-dependent EROD-activity is higher in rats than in minipigs. The dose
      response profile for renal CYP1A1 parallels that in the liver of either species
      but EROD-activities are 10-20 times lower than in the liver. Liver microsomal
      CYP2E1 is only slightly modulated in its expression by ingestion of PAH
      contaminated soils in both species, whereas CYP3A-dependent testosterone 2beta-
      and 6beta-hydroxylation is increased in liver of rats but not in minipigs. The
      hepatic capacity for catechol oestrogen formation, i.e., the 2-hydroxylation of
      17beta-oestradiol, is markedly increased in rats but not in minipigs by ingested
      PAH. It is concluded that different metabolic and transport pathways are used by
      minipigs and rats to process ingested PAH. Whereas in minipigs the duodenum
      appears as the first efficient barrier, rats respond by efficient metabolism in
      the liver. What is not known is which response profile is operative in man.

PMID- 15742976
TI  - Metabolism of human cytochrome P450 marker substrates in mouse: a strain and
      gender comparison.
AB  - The aim was to characterize mouse gender and strain differences in the metabolism
      of commonly used human cytochrome (CYP) P450 probe substrates. Thirteen human CYP
      probe substrates (phenacetin, coumarin, 7-ethoxy-4-trifluoromethyl coumarin,
      amiodarone, paclitaxel, diclofenac, S-mephenytoin, bufuralol, dextromethorphan,
      chlorzoxazone, p-nitrophenol, testosterone and lauric acid) were used in activity
      measurements. The metabolism of the probe substrates was compared in liver
      microsomes from male and female NMRI, CBA, C57bl/6, 129/SvJ and CD1 strains. The
      expression of proteins identified on Western blots with commonly available
      antibodies selective for specific human and rat CYP enzymes were compared in the
      different mouse strains. Males had higher metabolism than corresponding females
      for phenacetin O-deethylation (human marker for CYP1A2 activity), and a high
      correlation was found between phenacetin activity and immunoreactivity in Western
      blots produced with rat CYP1A2 antibodies. Protein detected by antibodies cross
      reacting with human CYP2B6 and rat CYP2B1/2 antibodies was female specific except
      for the 129/SvJ strain, where it was absent in both genders. Females generally
      had a higher metabolism of bufuralol 1'-hydroxylation and dextromethorphan O
      demethylation (human markers for CYP2D activity). Bufuralol 1'-hydroxylation
      correlated with a female-dominant mouse CYP, which was detected with antibodies
      against rat CYP2D4. p-Nitrophenol 2-hydroxylation correlated better than
      chlorzoxazone 6-hydroxylation with the protein detected with antibodies against
      rat CYP2E1, indicating that p-nitrophenol is a more specific substrate for mouse
      CYP2E1.

PMID- 15742977
TI  - Identification of the novel canine CYP1A2 1117 C > T SNP causing protein
      deletion.
AB  - The pharmacokinetics of YM-64227 (4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]
      pyrimidine-2-(1H)-one), a novel and selective phosphodiesterase type 4 inhibitor,
      was characterized in beagle dogs. Based on the plasma parent drug to major
      hydroxylated metabolite ratio, 21 dogs were phenotyped as 16 extensive
      metabolizers (EM) and five poor metabolizers (PM). Nucleotide sequences of CYPs
      1A2, 2B11, 2C21, 2D15, 2E1 and 3A12 were investigated in the EM and PM dogs. A
      CYP1A2 1117 C>T single nucleotide polymorphism was found, which resulted in an
      amino acid change from an Arg codon to a stop codon at position 373. All dogs
      phenotyped as PM were T/T homozygous, whereas EMs were C/C homozygous and C/T
      heterozygous. In Western blotting of liver microsomes, CYP1A protein expression
      was detected in the C/C and C/T types, but not in the T/T type. Of 65 dogs
      genotyped using genome DNA, the frequencies of the C and T alleles were 0.61 and
      0.39, respectively, suggesting approximately 15% of the dogs would not express
      the CYP1A2 protein. The findings provide a coherent explanation for the inter
      individual variability in the pharmacokinetics of CYP1A2 substrate drugs in dogs.

PMID- 15742978
TI  - Genetic polymorphisms of cytochrome P450 2C9 causing reduced phenprocoumon (S)-7
      hydroxylation in vitro and in vivo.
AB  - The effect of cytochrome P450 (CYP) 2C9 polymorphisms on the stereoselective
      biotransformation of the oral anticoagulant phenprocoumon (PPC) to inactive,
      monohydroxylated metabolites was studied in vitro and in vivo. In human liver
      microsomes, the (S)-7-hydroxylation--being the major metabolic pathway--was
      significantly compromised in a gene-dose-dependent manner in samples expressing
      the CYP2C9*2 or CYP2C9*3 allele. The CYP2C9*3/*3 genotype corresponded to an
      almost fourfold lower (S)-7-hydroxylation rate than CYP2C9*1/*1 (wild-type). The
      intrinsic clearance of human recombinant CYP2C9*2 and CYP2C9*3 for the (S)-7
      hydroxylation was 28.9 and 50.9% lower than of CYP2C9*1, respectively. The area
      under the plasma concentration-time curve (AUC) of PPC metabolites after oral
      intake of 12 mg racemic PPC was significantly lower in volunteers expressing the
      CYP2C9*2 or CYP2C9*3 allele. Increasing plasma AUC metabolic ratios (parent
      compound/metabolite) in CYP2C9*2 and CYP2C9*3 variant allele carriers were found
      for each hydroxylation reaction and the CYP2C9*3/*3 genotype corresponded to an
      about 10-fold higher metabolic ratio of PPC (S)-7-hydroxylation relative to
      CYP2C9*1/*1. CYP2C9 polymorphisms cause a markedly compromised PPC (S)-7
      hydroxylation. However, PPC metabolism appears overall less influenced by CYP2C9
      genotype compared with other oral anticoagulants and it may thus be a valuable
      alternative for therapeutic anticoagulation of patients expressing CYP2C9 variant
      alleles.

PMID- 15742980
TI  - An evaluation of quality of life of mothers of children with cerebral palsy.
AB  - PURPOSE: To evaluate the quality of life of mothers with children suffering from
      cerebral palsy compared with those who have children with minor health problems.
      METHOD: Forty mothers with a child suffering from cerebral palsy and 44 mothers
      with a child suffering from minor health problems participated in a comparative
      study. The Turkish version of the Medical Outcomes 36-Item Short Form Health
      Survey (SF-36) was used to assess a mother's quality of life. The severity of a
      child's motor disability was assessed using the Gross Motor Function
      Classification System (GMFCS). RESULTS: With the exception of the SF-36 physical
      functioning subscale, the mean scores on the SF-36 subscales were significantly
      lower in mothers of children with CP than those of the comparison group. The
      quality of life scores of mothers were significantly correlated with the severity
      of a child's motor disability (except physical functioning subscale). Significant
      correlations were found between GMFCS and the role physical; vitality; role
      emotional; and mental health subscales of the SF-36. CONCLUSIONS: The quality of
      life profile of mothers of children with cerebral palsy is different from those
      who have a child with minor health problems. Different coping strategies and
      psychosocial programmes must be designed and implemented to decrease the burden
      of care.

PMID- 15742979
TI  - Can the aspiration detected by videofluoroscopic swallowing studies predict long
      term survival in stroke patients with dysphagia?
AB  - PURPOSE: This study aimed to evaluate whether the aspiration detected by
      videofluoroscopic swallowing study (VSS) could predict the long-term survival in
      stroke patients with dysphagia in the post-acute phase of stroke. METHODS: A
      cohort of 182 consecutive patients with stroke-related dysphagia referred for VSS
      from July 1994 to April 1999 was retrospectively constructed. VSS findings and
      clinical features in the post-acute phase of stroke were recorded. The records
      thus obtained were then linked to the National Death Register to track the
      occurrence of patient deaths until December 31, 2000. RESULTS: Of the 182
      patients, 91 (50%) showed aspiration during VSS performed for a median duration
      of 8.4 weeks after stroke, and 76 (42%) had silent aspiration. In the post-acute
      phase of stroke (14.7 +/- 8.7 weeks after stroke, mean + standard deviation), 56
      (31%) were tube-fed, and 88 (48%) were wheelchair-confined. A total of 65
      patients died in a median follow-up duration of 30.8 months after VSS. Patients
      were classified into three groups based on the findings of VSS-detected
      aspiration or penetration, but no difference was noted in their survival curves.
      In the Cox stepwise regression analysis, only advanced age, recurrent stroke
      (hazard ratio 1.74, 95% CI 1.06-2.85), the need of tube-feeding (hazard ratio
      2.07, 95% CI 1.19-3.59), and being wheelchair-confined (hazard ratio 2.83, 95% CI
      1.54-5.19) during follow-up were independent predictors of long-term survival.
      CONCLUSIONS: VSS-detected aspiration during the post-acute phase of stroke was
      not predictive for the long-term survival in stroke patients with dysphagia.

PMID- 15742981
TI  - Falling in Parkinson's disease: the impact on informal caregivers.
AB  - PURPOSE: The aim of this study was to explore the views and experiences of the
      informal caregivers of repeat fallers with Parkinson's disease. METHOD:
      Individuals were invited to participate in this study if they were the informal
      caregiver of a person with Parkinson's disease (PD) who had experienced more than
      one fall in the previous 12 months. Participants were interviewed about their
      experience of managing falls using a semi-structured interview schedule.
      Interview data were transcribed and analysed using thematic analysis. RESULTS:
      Fourteen caregivers (11 female) participated in the study. All were marital
      partners of a repeat faller with Parkinson's disease. The average age of the
      participants was 69.9 years (44-79). Their partners had had PD for an average of
      16.7 years. Six major themes emerged from the analysis of the interview data,
      four directly related to falls management (the falls; consequences of the falls
      for the person with PD; caregivers' experiences of falls; consequences of falls
      for the caregiver). The majority of caregivers were frightened about their spouse
      falling. They used a number of methods of getting their spouse up from the floor
      but often injured themselves as a consequence. Caregivers highlighted the high
      level of care they provided and the social and psychological impact of the
      condition on them. They received limited help in looking after their spouse and
      little information about falls or about the disease in general. CONCLUSION:
      Caregivers in this study felt unprepared for their role and expressed a need for
      more support and advice, especially about managing falls.

PMID- 15742982
TI  - Whiplash injuries in Finland--the possibility of some sociodemographic and
      psychosocial factors to predict the outcome after one year.
AB  - PURPOSE: The aim of our study was to evaluate if there was any relation between
      the change experienced in the condition of health or the length of the reported
      sick leaves after one year of whiplash injury and different sociodemographic and
      psychosocial factors. METHOD: Our study design is a prospective 1-year-follow-up
      study. The material was collected in the year 1998 from neck injuries that had
      been caused by traffic accidents. The insurance companies sent a notice of the
      accident with medical certificate to the research team. After this we sent
      questionnaires to the injured and after one year of the accident a new inquiry
      was done. One hundred and eighty-two persons returned the 1-year-follow-up
      questionnaire which formed the material of this study. RESULTS: The persons who
      had the lowest basic education and people over 60 years of age had more health
      problems after one year of the accident. The other sociodemographic and
      psychosocial factors had only limited prognostic value when we evaluated the
      experienced change of health one year after the whiplash injury. Only 71 persons
      reported that they had been on sick leave because of the whiplash injury and of
      them only 21 reported sick leave over 1 month. CONCLUSIONS: Several
      sociodemographic and psychosocial factors can have relation to the deterioration
      of health experienced after whiplash injury but in this prospective study they
      proved to have only limited prognostic value in the long term symptoms with the
      exception of the education.

PMID- 15742983
TI  - A qualitative study of the consequences of 'hidden dysfunctions' one year after a
      mild stroke in persons <75 years.
AB  - BACKGROUND AND PURPOSE: Increased mental fatiguability, concentration and memory
      difficulties, irritability, emotional instability, impaired stress tolerance, and
      sound and light sensitivity, in this paper operationalized through the astheno
      emotional syndrome (AE syndrome) are known consequences of stroke. The aim of
      this study was to explore how persons with AE syndrome, one year after a mild
      stroke, experienced the consequences of the syndrome in everyday life. METHOD: A
      qualitative design was used. Fifteen respondents were chosen by strategic
      sampling and interviewed. The analysis was done using a grounded theory method.
      RESULTS: Data analysis yielded harmed/threatened self as the core category with
      four main categories covering the dimensions of: hidden-apparent dysfunction,
      predictability-unpredictability, independence-dependence and active life-passive
      life. The model grounded in data shows the structural properties and the
      processes that verify the dynamics and interactions of the everyday life
      consequences of AE syndrome. CONCLUSIONS: AE syndrome with mental fatiguability
      as the most common symptom affected many dimensions of everyday life, which in
      turn affected performance of activities and independence. The symptoms were
      'hidden' in many ways, not only indetectable in the appearance of the person, but
      also on a more symbolic level not apparent to the patient and persons in their
      environment. The symptoms changed with environmental circumstances and were
      experienced as unpredictable.

PMID- 15742985
TI  - Living with a chronic deteriorating disease: the trajectory with muscular
      dystrophy over ten years.
AB  - PURPOSE: The aim of the study was to elucidate experiences of living with
      muscular dystrophy in terms of consequences for activity over 10 years. METHODS:
      The study population was identified in a prevalence study in a county of Sweden.
      Forty-six persons of this cohort with MD were interviewed. A qualitative research
      approach was chosen. The World Health Organization's International Classification
      of Functioning, Disability and Health (ICF) was used for categorization. RESULTS:
      Nearly all the subjects experienced a deterioration of physical capacity. Most
      obvious were the restrictions on mobility and increased fatigue and feebleness.
      The persons described psychosocial consequences of the muscular dystrophy as well
      as stigma when the disability had become more obvious. In spite of reported
      distress several persons experienced better psychological adaptation over time.
      The image of the future was often dark but several focus on today and avoid
      thoughts about the future. ICF showed some limitation with regard to temporal
      aspects, emotions and the subjective perspective. CONCLUSIONS: The knowledge of
      the trajectory with MD is important in order to offer the best possible treatment
      and support. Repeated assessment by ICF can serve as a valuable source of such
      knowledge, and a development of the classification would increase its usefulness
      in future analysis of functioning and disability.

PMID- 15742984
TI  - Cognitive impairment after transurethral resection of the prostate (TURP).
AB  - PURPOSE: It has been suggested that cognitive impairment may occur following
      transurethral resection of the prostate (TURP) operations due to the effects of
      anaesthesia or hyponatraemia or both. The aim of the study was to investigate
      whether TURP was associated with long-term memory complaints or cognitive
      impairment. METHOD: Patients who had received a TURP or transurethral resection
      of a bladder tumour (TURT) in the previous 10 months were sent a questionnaire on
      memory problems and mood. Seventy-six TURP patients and 38 TURT patients returned
      the completed questionnaires. A sample of each patient group (30 TURP, 29 TURT)
      was assessed on standardized tests of cognitive abilities. RESULTS: There was no
      significant difference between the TURP and TURT patients on the Everyday Memory
      Questionnaire completed by themselves or by a family member (p > 0.05). On formal
      cognitive testing there were no significant differences between the groups,
      except on the overall grading of the Kendrick Assessment Scales of Cognitive
      Ageing, in which TURP patients performed at a significantly lower level than TURT
      patients. CONCLUSIONS: The results suggest that patients are no more likely to
      complain of memory problems following a TURP than with any other operative
      procedure. There was a slight difference in cognitive abilities but this did not
      indicate significant impairment of cognitive function.

PMID- 15742986
TI  - Screening Internet websites for educational potential in undergraduate medical
      education.
AB  - This paper addresses the difficulty of finding suitable websites to support
      undergraduate medical students in learning key concepts and skills in plastic
      surgery in particular, and other areas of undergraduate medical education in
      general. Based on a model of the pedagogical elements contained in educational
      websites, the authors developed a short objective scoring system with five
      criteria. Pre-university students were used to find websites in plastic surgery.
      One hundred and fifty of those that were still in place after a year were
      evaluated using the objective scoring system. Sixty of these were then selected
      and were subjectively evaluated by final year medical students in terms of their
      perceived educational potential. There was only a moderate correlation between
      the objective and subjective scores. Our conclusion is that it does not seem
      possible to construct any objective system of medical website evaluation. The
      discussion of the results of this study focuses on the issues involved in finding
      suitable web-based material and the diversity between students. New strategies
      such as formally organized consortia involving agreements between medical schools
      may evolve.

PMID- 15742987
TI  - A system for symptom assessment in advanced palliative home healthcare using
      digital pens.
AB  - Symptom control is one of the most important components of delivering effective
      palliative care, and adequate symptom assessment is a prerequisite for good
      symptom control. Patients receiving treatment in palliative home healthcare is
      geographically separated from the caregivers making symptom control a challenge,
      a challenge that could be met by the use of information and communication
      technology. Technologies of today offer different ways for patients to assess
      their symptoms at home and send the assessments to the healthcare provider.
      Examples are the use of a PC, a touch-tone telephone, and a digital pen, which
      require different kinds of infrastructure in the patient's home, and which differ
      in strengths and weaknesses. As part of an ongoing quality assurance work within
      the hospital-based home care clinic at Linkoping University Hospital, the project
      has designed, developed and implemented an IT-support system for pain assessments
      for patients at home using digital pen and mobile Internet technology. A
      questionnaire study indicated that pain assessment using digital pens was
      accepted by patients and that problems mainly arose from the use of the visual
      analogue scale.

PMID- 15742988
TI  - Reporting on post-menopausal hormone therapy: an analysis of gynaecologists' web
      pages.
AB  - BACKGROUND: The present study was designed to analyse Web pages of German
      gynaecologists with regard to postmenopausal hormone therapy (HT). There is a
      growing body of evidence, that the overall health risks of HT exceed the
      benefits. Making one's own informed choice has become a central concern for
      menopausal women. The Internet is an important source of health information, but
      the quality is often dubious. The study focused on the analysis of basic criteria
      such as last modification date and quality of the HT information content. The
      results of the Women's Health Initiative Study (WHI) were used as a benchmark.
      METHODS: We searched for relevant Web pages by entering a combination of key
      words (9 x 13 = 117) into the search engine www.google.de. Each Web page was
      analysed using a standardized questionnaire. The basic criteria and the quality
      of content on each Web page were separately categorized by two evaluators.
      Disagreements were resolved by discussion. MAIN FINDINGS: Of the 97 websites
      identified, basic criteria were not met by the majority. For example, the
      modification date was displayed by only 23 (23.7%) Web pages. The quality of
      content of most Web pages regarding HT was inaccurate and incomplete. Whilst only
      nine (9.3%) took up a balanced position, 66 (68%) recommended HT without any
      restrictions. In 22 cases the recommendation was indistinct and none of the sites
      refused HT. With regard to basic criteria, there was no difference between HT
      recommending Web pages and sites with balanced position. CONCLUSION: Evidence
      based information resulting from the WHI trial was insufficiently represented on
      gynaecologists' Web pages. Because of the growing number of consumers looking
      online for health information, the danger of obtaining harmful information has to
      be minimized. Web pages of gynaecologists do not appear to be recommendable for
      women because they do not provide recent evidence-based findings about HT.

PMID- 15742989
TI  - Which are the best identifiers for record linkage?
AB  - As a linkage using less informative identifiers could lead to linkage errors, it
      is essential to quantify the information associated to each identifier. The aim
      of this study was to estimate the discriminating power of different identifiers
      susceptible to be used in a record linkage process. This work showed the interest
      of three identifiers when linking data concerning a same patient using an
      automatic procedure based on the method proposed by Jaro; the date of birth, the
      first and the last names seemed to be the more appropriate identifiers. Including
      a poorly discriminating identifier like gender did not improve the results.
      Moreover, adding a second christian name, often missing, increased linkage
      errors. On the contrary, it seemed that using a phonetic treatment adapted to the
      French language could improve the results of linkage in comparison to the
      Soundex. However, whatever, the method used it seems necessary to improve the
      quality of identifier collection as it could greatly influence linkage results.

PMID- 15742990
TI  - Analysis of cost and assessment of computerized patient record systems in Japan
      based on questionnaire survey.
AB  - PURPOSE: The purpose of this study was to clarify the implementation and
      maintenance costs of a computerized patient record (CPR) system by means of a
      questionnaire survey. Moreover, the benefits of CPR systems were evaluated to
      determine their contribution to enhancing the quality of medical care and
      hospital management. METHODS: Data were collected by a questionnaire survey
      mailed out to participants. RESULTS: The per-bed mean cost for implementation was
      14,308 dollars (range: 3538-38,077 dollars). The mean annual maintenance cost for
      the CPR system was 457,615 dollars (range: 39,769-2,307,692 dollars). The
      multivariate analysis (Hayashi's Quantification Type I) revealed high partial
      correlation coefficients between implementation cost and the CPR system maker. In
      addition, the multiple correlation coefficient for four factors (CPR system
      maker, number of servers, institution type and implementation date) in predicting
      implementation cost was 0.798. Over 60% of respondents replied that their
      satisfaction with the CPR system was 'very high' or 'high.' Eighty-two percent of
      the hospitals responded positively that CPR systems improve the quality of
      medical care, and 70% felt that the systems help prevent medical errors.
      CONCLUSIONS: Our findings indicate that the maker of CPR system, number of
      servers, institution type and implementation date had a strong influence on per
      bed implementation costs in that order. Finally, it was found that CPR systems
      were considered effective for hospital administration and medical examinations,
      based on the high assessments of the results of installing a CPR system.

PMID- 15742992
TI  - Oesophageal cancer incidence and mortality in patients with long-segment
      Barrett's oesophagus after a mean follow-up of 12.7 years.
AB  - BACKGROUND: Data on cancer risk in patients with long-segment Barrett's
      oesophagus (BO) from older studies are often difficult to interpret, since the
      definition of BO has evolved from an endoscopical to a histological diagnosis. In
      this work the diagnoses in the Rotterdam BO cohort on current standards was
      redefined to obtain more accurate data on cancer risk in patients who had not
      undergone standard endoscopic surveillance. In addition, it was determined which
      patient factors present at index endoscopy were associated with neoplastic
      progression in BO. METHODS: The Rotterdam BO cohort comprises all patients with >
      or =3 cm BO, diagnosed at endoscopy between 1973 and 1984. In the present study,
      only patients with intestinal metaplasia were included (n = 105). Follow-up data
      were obtained by questionnaires and/or interviews with patients or treating
      physicians. A Kaplan-Meier analysis was used to estimate 20-year risks. RESULTS:
      The mean length of the BO was 7.1 cm (range: 3-15 cm). Cancer in BO developed in
      6/105 (6%) patients, and high-grade dysplasia (HGD) in 5/105 (5%) patients during
      1329 patient-years of follow-up, which equals one cancer case per 221 patient
      years and one HGD case per 266 patient-years. After a mean follow-up of 12.7
      years, 72 (69%) patients had died; only 4 of them died of oesophageal cancer or
      its treatment. A longer length of BO was associated with an increased risk of
      progression to HGD or cancer (P < 0.02). Six of 24 patients who ever had low
      grade dysplasia progressed to HGD or cancer 2-16 years after a diagnosis of BO.
      CONCLUSIONS: The annual risk of developing HGD or adenocarcinoma in patients with
      long-segment BO is 0.83%. Death due to adenocarcinoma is, however, uncommon, even
      in a cohort of patients with long-segment BO.

PMID- 15742991
TI  - The design and evaluation of clinical decision support systems in the area of
      pharmacokinetics.
AB  - Gentamicin, an antibiotic drug, can be used in one-sided (unilateral) Meniere's
      disease to end frequent attacks of spontaneous disabling vertigo. However, with
      incorrect dose treatment it can profoundly damage patients' inner ear and kidney.
      The dosage of medication and the dosage interval will affect serum concentration
      that results therapeutic or damage. Pharmacokinetics is the study of managing the
      relationship between the dosage medication, dosing interval, and serum
      concentration. However, due to the complicated mathematical equations of
      pharmacokinetics, it is rarely used in clinics. The purpose of this study was to
      use a pharmacokinetics model to build a prototype of gentamicin CDSS embedded in
      a PDA. This system was implemented in a district teaching hospital in Chiayi
      area, Taiwan. Empirical data was collected under routine clinical setting with
      real patients and physicians to validate this CDSS. The research results showed
      that, considering the therapeutic effect, the pharmacokinetics-based CDSS
      outperforms physicians' experience. Regarding the intoxication, the
      pharmacokinetics-based CDSS also performed better than physicians' experience
      with less intoxication. The physicians using the system revealed a high degree of
      agreement with the perceived usefulness, perceived ease of use, and intention to
      use the pharmacokinetics-based CDSS.

PMID- 15742993
TI  - Clinical significance of cytotoxin-associated gene A status of Helicobacter
      pylori among non-steroidal anti-inflammatory drug users with peptic ulcer
      bleeding: a multicenter case-control study.
AB  - BACKGROUND: The role of Helicobacter pylori infection and especially of the
      cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among
      non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial.
      METHODS: A case-control study was carried out including 191 consecutive chronic
      NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer
      was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without
      signs of bleeding of similar age and gender to cases. Multivariate regression
      analysis was performed for further evaluation of the relationship between H.
      pylori, CagA status and other risk factors. RESULTS: H. pylori infection was
      present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR)
      = 1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly
      more frequent in cases than in controls (65/106 versus 41/99 P = 0.008). Current
      smoking (OR = 2.65; 95% CI, 1.14-6.15; P= 0.02), CagA status (OR = 2.28; 95% CI,
      1.24-4.19; P = 0.008), dyspepsia (OR = 6.89; 95% CI, 1.84-25.76; P = 0.004) and
      past history of peptic ulcer disease (OR=3.15; 95% CI, 1.43-6.92; P=0.004) were
      associated significantly with increased risk of bleeding peptic ulcer.
      CONCLUSIONS: The results suggest that CagA-positive H. pylori infection is
      associated with a more than 2-fold increased risk of bleeding peptic ulcer among
      chronic NSAIDs users.

PMID- 15742994
TI  - Long-term recurrence rate after treatment of Helicobacter pylori infection in
      children and adolescents in Estonia.
AB  - BACKGROUND: Helicobacter pylori infection is common in Estonia: 87% of adults and
      56% of children aged 9-15 years have been found to be H. pylori seropositive. The
      aim of this study was to evaluate the long-term recurrence rate after treatment
      in children and adolescents in a setting of high H. pylori prevalence. METHODS:
      All children (n = 27) who underwent gastroscopy at the Children's Clinic of Tartu
      University Clinics during 1993--95 and in whom H. pylori infection was verified
      by histological examination and rapid urease test and who had completed a
      treatment course against H. pylori infection were invited for a post-treatment
      follow-up endoscopy 4-6 weeks after completion of therapy (1st follow-up visit)
      and to the follow-up control by [13C]-urea breath test in 1997 (2nd follow-up
      visit) and 2002 (3rd follow-up visit). RESULTS: Recurrence of H. pylori infection
      occurred in I patient out of 16 at the 2nd follow-up visit (mean 17.8+/-7.1
      months after treatment), and in 5 patients out of 15 at the 3rd follow-up visit
      (mean 6.6+/-0.9 years after treatment). The recurrence rate calculated for the
      period between the 1st and the 2nd follow-up visits was 4.2% per patient-year,
      and between the 2nd and the 3rd follow-up visits the rate was 7.6% (95% CI 2.5%
      17.6%) per patient-year. The recurrence rate calculated for the whole follow-up
      period was 6.7% (95% CI 2.5%-14.5%) per patient-year. CONCLUSION: The post
      treatment recurrence rate of H. pylori infection in children and adolescents is
      higher in Estonia than in low prevalence settings.

PMID- 15742995
TI  - Gene expression in gastric biopsies from patients infected with Helicobacter
      pylori.
AB  - BACKGROUND: Helicobacter pylori infection has protean effects on gene expression
      in the host gastric mucosa, which have been investigated by gene chip analysis in
      vitro. In this study the effects of H. pylori infection on host gene expression
      in the gastric antral mucosa in patients were examined. METHODS: One gastric
      antral biopsy was obtained from a total of 18 untreated patients undergoing
      routine endoscopic evaluation of chronic abdominal complaints. Nine patients had
      histologic evidence of H. pylori infection and 9 age- and sex-matched patients
      had no histologic evidence of H. pylori infection. A microarray analysis was
      performed using a gene chip containing 35,000 human expressed sequence tags on
      RNA extracted from endoscopic, gastric antral biopsies, and average gene
      expression among infected and uninfected patients was compared. RESULTS:
      Underexpressed genes in infected patients' mucosa included gastric intrinsic
      factor and several metallothionein isoforms. Overexpressed genes in infected
      patients' mucosa comprised MHC Class II molecules, immunoglobulin and B-cell
      activation genes, as well as genes known to induce apoptosis. Changes in
      expression were confirmed for a subset of genes by SYBR green real-time PCR.
      CONCLUSIONS: Microarray analysis of antral biopsies from patients with and
      without H. pylori infection revealed differential expression of metal regulatory,
      immunity and inflammation-related genes.

PMID- 15742996
TI  - Validation of the translation and cross-cultural adaptation into Finnish of the
      Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale and
      the Complaint Score Questionnaire.
AB  - BACKGROUND: Epidemiological surveys require questionnaires to be validated in the
      native language of the participants. The aim of this study was to validate the
      Finnish translations of the Abdominal Symptom Questionnaire (ASQ), the Hospital
      Anxiety and Depression Scale (HAD) and the Complaint Score Questionnaire (CSQ).
      METHODS: A random sample of adults (n = 3000) in a northern Swedish bilingual
      district was surveyed using a mailed ASQ offered in both SwedIsh and Finnish, and
      2122 responded (239 in Finnish). A random subsample of the responders (n = 1001,
      123 preferring Finish) was then surveyed once more using the ASQ, the HAD and the
      CSQ. The first 50 responders of the latter survey were then given the three
      questionnaires again within two weeks. The Finnish versions had been put through
      a comprehensive translation procedure RESULTS: A factor analysis comparison
      between the responders using either language in the mailed survey gave a
      comparable factor construction, and this was also comparable with an earlier
      analysis of the Swedish version. The Finnish responses to the second survey were
      further evaluated by testing internal consistency reliability, convergent
      validity towards previously validated relevant instruments (ShortForm-36 and the
      Gastrointestinal Symptom Rating Scale) and the test/re-test accuracy of the three
      questionnaires. These were found to be reliable, as was the correlation between
      the ASQ and the CSQ, for relevant domains. CONCLUSION: The Finnish translations
      of the ASQ, HAD and CSQ questionnaires all seem to be robust and usable for
      population-based surveys among Finnish adults.

PMID- 15742997
TI  - Ghrelin enhances gastric motility through direct stimulation of intrinsic neural
      pathways and capsaicin-sensitive afferent neurones in rats.
AB  - BACKGROUND: Ghrelin may stimulate gastric motility via the vagal nerve pathway.
      However, the mechanism of ghrelin-induced changes in gastrointestinal motility
      has not yet been clearly defined. The present study was designed to investigate
      whether ghrelin accelerates gastric emptying via capsaicin-sensitive afferent
      neurones and directly affects the enteric neuromuscular function. METHODS:
      Gastric emptying of nutrient solids was assessed after intravenous administration
      of saline or ghrelin in conscious rats. The effects of ghrelin on gastric
      emptying were also examined in rats pretreated with capsaicin. Gastric emptying
      and intestinal transit of non-caloric liquids were evaluated using 51Cr solution.
      The effects of ghrelin on spontaneous contractile activities of isolated strips
      from stomach and jejunum were also investigated and the influence of ghrelin on
      motor responses to carbachol and electrical field stimulation was examined.
      RESULTS: Ghrelin significantly accelerated gastric emptying of both nutrient
      solids and non-caloric liquids in conscious rats. The intestinal transit of non
      caloric liquids was also enhanced by ghrelin. Pretreatment with capsaicin
      prevented the ghrelin-induced acceleration of gastric emptying of nutrient
      solids. Ghrelin did not modulate spontaneous and carbachol-induced contractions
      of strips of gastric body, gastric antrum and jejunum. However, electrical field
      stimulation-induced contractions were significantly enhanced by ghrelin in the
      gastric body. CONCLUSIONS: The results suggest that the stimulatory effects of
      ghrelin on gastric motility are mediated by direct stimulation of the enteric
      neural pathway and capsaicin-sensitive afferent neurones.

PMID- 15742998
TI  - Gastric clearance of radiopaque markers in the evaluation of gastric emptying
      rate.
AB  - BACKGROUND: The study of gastric emptying rate of solids using radiopaque
      indigestible solid markers has been a poorly employed technique because some
      kinds of markers do not leave the stomach at the same time as the meal but during
      the interdigestive migrating motor complex (IMMC). The aim of this study was to
      evaluate whether markers of particular shape and size can be successfully
      employed for this purpose. METHODS: Twenty-eight non-ulcer dyspeptic (NUD)
      patients and 20 healthy volunteers received a standard solid meal (790 Kcal)
      together with 20 small polyethylene radiopaque cylinders (5 mm x 2 mm in
      diameter). Gastric emptying rate was evaluated by ultrasound while the emptying
      of markers was simultaneously followed by X-rays using a brilliance intensifier.
      RESULTS: Final emptying time (FET = time when the antrum area returns to fasting
      size) of digestible solids was 355+/-35 min in NUD patients versus 265+/-20 min
      in controls (P < 0.001). The gastric emptying curve of digestible solids
      correlated with emptying of markers both in NUD patients (r= +0.96) and in
      controls (r= +0.93). CONCLUSIONS: The assessment of gastric clearance of
      radiopaque cylinders of 2 mm x 5 mm in size is a reliable tool for the study of
      gastric emptying rate of digestible solids. This is a readily available and
      easily performed test in any radiology unit.

PMID- 15742999
TI  - Intestinal tissue transglutaminase in coeliac disease of children and adults:
      ultrastructural localization and variation in expression.
AB  - BACKGROUND: Tissue transglutaminase is the main antigen for the anti-endomysial
      antibodies used for diagnosis of coeliac disease and can with some specificity in
      vitro deamidate gliadins generating potent epitopes. The intestinal levels and
      the ultrastructural localization of tissue transglutaminase in normal and
      affected persons were investigated to provide further information on its role in
      this disease. Intestinal biopsies were taken from normal and coeliac children and
      adults. METHODS: The level of transglutaminase was analysed by means of a
      quantitative enzymatic assay and its ultrastructural localization by immunogold
      electronmicroscopy using a monoclonal antibody against tissue transglutaminase.
      RESULTS: In relation to normal individuals, the enzymatic activity of tissue
      transglutaminase in adult coeliac patients was increased. The enzyme was found in
      the enterocytes and in increased amount just beneath the enterocytes, where
      cytosolic and nuclear labelling of distinct elongated cells was seen in addition
      to extracellular labelling close to collagen fibrils. In children, the enzymatic
      activity and the immunogold labelling could not be shown to be related to
      disease. In all cases the enzyme activity was EDTA-sensitive. CONCLUSIONS: The
      increased amount of tissue transglutaminase activity in coeliac adults was shown
      to be due to the appearance of the enzyme in enterocytes and increased expression
      in the lamina propria. No evidence was found to support the idea of a changed
      localization or changed amounts as primary elements in coeliac disease
      pathogenesis, nor for the involvement of non-calcium dependent microbial
      transglutaminases.

PMID- 15743000
TI  - Assessment of mucosal inflammation and blood flow in response to four weeks'
      intervention with probiotics in patients operated with a J-configurated ileal
      pouch-anal-anastomosis (IPAA).
AB  - BACKGROUND: Pouchitis is a common and troublesome condition in patients operated
      on with ileal-pouch-anal-anastomosis (IPAA). A disturbed mucosal perfusion in the
      pouch has been suggested as a possible cause. Laser Doppler flowmetry (LDF) has
      been used successfully to measure gastric and colonic mucosal perfusion in
      humans. In a previous study, we demonstrated a reduced mucosal perfusion in the
      distal part of the pouch, during probiotic intervention, examined by LDF
      measurement. The aim of the present study was to confirm our previous results in
      a much larger material, and to compare the results of LDF measurements and
      inflammatory activity in ulcerative colitis (UC) patients with those in familial
      adenomatous polyposis (FAP) patients. METHODS: Five hundred millilitres of a
      fermented milk product (Cultura), containing live lactobacilli (La-5) and
      bifidobacteria (Bb-12), was given daily for 4 weeks to 41 UC and 10 patients with
      FAP, operated on with IPAA. Mucosal perfusion was measured with LDF and the
      degree of inflammation was examined at predefined levels of the distal bowel by
      histology and faecal calprotectin measurements both before and after
      intervention. We also evaluated the applicability of a Pouchitis Disease Activity
      Index (PDAI). RESULTS: The LDF measurements were reproducible in the pelvic pouch
      at each of the predefined levels, but did not change during intervention. Mucosal
      perfusion was significantly reduced in the distal compared to the proximal part
      of the pouch in the UC group (P < 0.05). The perfusion levels were higher in the
      FAP patients compared to the UC patientsat all predefined levels (P < 0.05).
      Calprotectin levels and histological score did not change significantlyafter
      intervention in any of the groups. The calprotectin level was significantly lower
      in the FAP compared to the UC group both before and after intervention. The PDAI
      decreased in both groups from alevel considered diagnostic for pouchitis to a
      level considered as not active pouchitis. The decreasewas significant for the UC
      patients. CONCLUSIONS: The results did not demonstrate an effect of probiotics on
      histology, although a significant effect on the PDAI was achieved, which concurs
      with the previously reported effect on symptoms and endoscopic score. The
      significantly reduced blood flow in the UC group compared to the FAP group,
      operated on with the same procedure, and the significantly increased calprotectin
      levels in the UC group, are original findings. Both findings may be related to an
      increased risk for pouchitis among UC patients. The lack of effect of
      intervention on mucosal perfusion does not exclude a role for reduced circulation
      as a cause of pouchitis based on the reduced LDF measurements in the distal part
      of the pouch.

PMID- 15743001
TI  - Higher proliferative capacity of T lymphocytes from patients with Crohn disease
      than from ulcerative colitis is disclosed by use of Herpesvirus saimiri
      transformed T-cell lines.
AB  - BACKGROUND: T lymphocytes play a crucial role in the pathogenesis of inflammatory
      bowel disease. Achieving stable T-cell lines, rather than continuous bleeding of
      patients, is desirable in order to dissect their implication in the disease.
      METHODS: Long-lasting T-cell lines from patients with Crohn disease and
      ulcerative colitis and from healthy volunteers have been obtained by
      transformation of T lymphocytes using the lymphotropic Herpesvirus saimiri. Lines
      were subjected to phenotypic and functional analyses, and the results compared
      with freshly isolated peripheral blood mononuclear cells. RESULTS: Fresh cells
      revealed only minor differences between patients and controls, with regard to
      phenotype and proliferative capacity. In contrast, the use of T-cell lines showed
      that cells from Crohn disease patients, but not ulcerative colitis patients, over
      responded to several membrane or cytoplasmic stimuli when compared to control T
      cell lines. Thus, higher responses were found when stimulated with alphaCD3 and
      IL2, alphaCD3 and alphaCD28, IL2 alone, phorbol esters (PMA) and alphaCD3 and,
      finally, PMA and alphaCD2 (P < 0.05 in all instances). Further, lines from
      patients with Crohn disease responded more vigorously to alphaCD3 and alphaCD28
      or alphaCD3 and PMA when compared to ulcerative colitis (P < 0.05 in both
      instances). CONCLUSIONS: The data obtained with these lines suggest that T cells
      from patients with Crohn disease differ in vivo in their proliferative capacity,
      as compared with those from ulcerative colitis patients, a finding that may
      reflect the clear Th-1 phenotype found in the former and absent in the latter.

PMID- 15743002
TI  - CARD15 frameshift mutation in patients with CROHN disease is associated with
      immune dysregulation.
AB  - BACKGROUND: Mutations in the caspase-activating recruitment domain 15 (CARD15)
      gene are associated with Crohn disease (CD). CARD15 is an intracellular receptor
      for bacterial lipopolysaccharides (LPS). LPS-induced activation of transfectants
      containing the frameshift mutation (1007fs) of CARD15 is impaired. The aim of
      this study was to investigate whether the presence of CARD15 1007fs affects
      activation of CD patients' own cells. Patients (4 homozygotes, 6 heterozygotes,
      and 6 wild-type) were matched according to clinical picture and medication.
      METHODS: Immune inflammatory status was evaluated by measuring monocyte HLA-DR
      and CD11b densities and the proportion of CD14dimCD16+ monocytes, and was found
      to be comparable in the three groups. Blood mononuclear cells were cultured
      overnight in serum-free medium alone, or the medium supplemented with LPS (0.1
      10.0 ng/mL), a combination of IFN-gamma (100 IU/mL) and granulocyte-macrophage
      colony stimulating factor (GM-CSF) (5 ng/mL), or both. TNF and IL-10 levels in
      the culture supernatant were determined. RESULTS: LPS 0.1 or 1.0 ng/mL alone did
      not increase TNF levels. IFN-gamma/GM-CSF induced TNF release, and co-culture
      with LPS 1.0 or 10.0 ng/mL was strongly synergistic. CARD15 1007fs mutation was
      linked in a gene-dose-dependent manner to low TNF release induced by IFN-gamma/GM
      CSF (P value for linear trend = 0.001). The degree of synergism in co-culture was
      normal or high, suggesting that 1007fs did not depress responses to LPS. IL-10
      levels were not related to CARD15 1007fs. CONCLUSIONS: In CD patients, CARD15
      1007fs is associated in a gene-dose-dependent manner to low mononuclear cell TNF
      release by IFN-gamma/GM-CSF but does not impair TNF release by LPS. This type of
      immune dysregulation may influence susceptibility to and/or phenotype of CD.

PMID- 15743003
TI  - Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene
      sulphonic acid-induced colitis in rats.
AB  - BACKGROUND: It has recently been shown that Lactobacillus farciminis treatment
      exerts an anti-inflammatory effect in trinitrobenzene sulphonic acid (TNBS)
      induced colitis partly through a nitric oxide release by this strain. The aim of
      this study was to evaluate whether L. farciminis treatment shares also the
      general mechanisms of action involved in the beneficial effect of probiotics in
      the colonic inflammatory process. METHODS: Rats received L. farciminis for 15
      days before and 4 days after intracolonic administration of TNBS or vehicle. The
      following parameters were evaluated: macroscopic damage of colonic mucosa,
      myeloperoxidase activity, cytokine mucosal levels, bacterial profile in colonic
      content and mucosa, bacterial translocation and colonic paracellular
      permeability. RESULTS: In the absence of TNBS, L. farciminis treatment reduced
      colonic paracellular permeability and increased the IL-10 level in the colonic
      wall. TNBS administration induced colonic macroscopic damage, associated with an
      increase of myeloperoxidase activity, bacterial translocation, colonic
      paracellular permeability and IL-1beta mucosal level, and a decrease in IL-10
      mucosal level. Moreover, the bacterial profile of colonic content and mucosa was
      modified. All these alterations were abolished or significantly reduced by L.
      farciminis treatment. CONCLUSIONS: As previously shown, L. farciminis treatment
      improves TNBS-induced colitis. This study indicates that, in addition to the
      nitric oxide released by this bacterial strain, the anti-inflammatory action of
      L. farciminis involves also normalization of colonic microflora, prevention of
      bacterial translocation, enhancement of barrier integrity and a decrease in the
      IL-1beta mucosal level.

PMID- 15743004
TI  - Familial risk of tumors associated with hereditary non-polyposis colorectal
      cancer: a Swedish population-based study.
AB  - BACKGROUND: Familial clustering, which may be due to inherited predisposition, is
      seen in several common cancer types. The aim of this study was to assess the
      familial risk of tumors that are associated with hereditary non-polyposis
      colorectal cancer (HNPCC), a familial cancer syndrome that confers an increased
      risk of several cancer types, and is associated with a low age at onset. METHODS:
      The National Swedish Cancer Registry and population registers were utilized to
      identify all tumors among the offspring of individuals who had developed any of
      the diagnoses included in the Amsterdam II criteria for HNPCC. In all, 204,358
      offspring of 102,814 individuals with cancer of the colorectum, endometrium,
      upper urinary tract or small intestine were identified. RESULTS: Significantly
      increased risks for several tumor types were demonstrated. If the parent was
      below age 50 at diagnosis, the offspring Standard Incidence Ratios (SIRs) were
      3.6 for colon cancer, 3.8 for rectal cancer, 2.8 for gastric cancer, and 2.3 for
      ovarian cancer. Offspring who had both a parent and a sibling with HNPCC
      associated cancer showed even higher SIRs for cancer of the colorectum,
      endometrium, ovary, and urinary tract. The highest values were observed in the
      subgroup whose parent had developed multiple primary tumors; SIR 34.0 for colon
      cancer, 17.9 for rectal cancer, 21.8 for endometrial cancer, and 5.8 for ovarian
      cancer. CONCLUSIONS: The study demonstrates that there is an increased risk for
      several tumor types among individuals whose parents developed HNPCC-associated
      tumors, where a young age at diagnosis and development of multiple tumors in the
      parents lead to the highest SIRs.

PMID- 15743005
TI  - Bifidobacterium animalis strain DN-173 010 hydrolyses bile salts in the
      gastrointestinal tract of pigs.
AB  - BACKGROUND: Bile salt hydrolase (BSH) activity is widespread among ingested
      bifidobacteria and lactobacilli. It is sometimes considered to be beneficial
      because of its putative lowering effect on cholesterol absorption and sometimes
      considered to be deleterious because it may compromise normal fat absorption and
      even promote the formation of secondary cytotoxic bile acids by the resident
      intestinal flora. However, the true hydrolysis of bile salts in vivo by ingested
      living bacteria remains unexplored. The aim of the study was to examine whether
      or not Bifidobacterium animalis DN-173 010 (used in fermented milks), which
      demonstrates a BSH activity in vitro, was also active in vivo during its transit
      in the intestine of pigs. METHODS: Direct measurement of total and unconjugated
      bile acids reabsorbed into the portal vein was done, before and after the pigs
      had been treated for 2 weeks with two daily doses of approximately 3.5 x 10(11)
      colony-forming units of living (6 pigs) or inactivated B. animalis (6 pigs).
      RESULTS: None of the treatments modified the portal serum concentration of total
      bile acids over a 6-h postprandial period. Unconjugated bile acids represented up
      to 44% and 53% of total bile acids after 1 and 2 weeks of treatment with living
      bacteria, respectively, compared with only 25% (P < 0.05) before treatment or
      after 1 or 2 weeks of treatment with inactivated bacteria. CONCLUSIONS: Living B.
      animalis DN-173 010 exhibited a BSH activity in the gastrointestinal tract of
      pigs, most probably in the small bowel. There was no sign of increased formation
      of secondary bile acids beyond the hydrolysis reaction.

PMID- 15743006
TI  - Prognostic index of liver cirrhosis with ascites with and without hepatocellular
      carcinoma.
AB  - BACKGROUND: In Japan, the incidence of liver cirrhosis caused by hepatitis
      viruses is higher, and cirrhosis is more likely to be complicated by
      hepatocellular carcinoma, than in Western countries. The aim of this study was to
      predict the outcome in liver cirrhosis with ascites with and without
      hepatocellular carcinoma. METHODS: The subjects were 146 patients with liver
      cirrhosis complicated by ascites. Forty-six factors were evaluated concerning
      clinical laboratory parameters and extracted prognostic factors using the Cox
      proportional hazards model. RESULTS: The mean duration of the follow-up period
      was 634.9 days, during which 89 (61%) of the patients died, 27 (18.5%) survived,
      and 30 (20.6%) were lost to follow-up. The cumulative survival rate after the
      onset of ascites was 59.7% after 1 year, 44.5% after 2 years, and 29.5% after 5
      years. Multivariate analysis indicated 9 factors, i.e. age, total bilirubin (T
      Bil), alkaline phosphatase (ALP), blood urea nitrogen (BUN), alpha-fetoprotein
      (AFP), mean arterial pressure (MAP), gastrointestinal bleeding, infection, and
      portal vein tumor thrombosis (PVTT), as independent prognostic factors. The
      prognostic index (PI) was calculated by the following formula using these 9
      factors. PI = 0.045 x age + 0.180 x T-Bil + 0.088 x ALP + 0.020 x BUN + 0.467 x
      AFP + (-0.022 x MAP) + 0.662 x gastrointestinal bleeding + 0.521 x infections +
      0.882 x PVTT. CONCLUSION: Prediction of the outcome using PI based on the 9
      factors provides additional information for the determination of the therapeutic
      approach in cirrhotic patients with ascites with and without hepatocellular
      carcinoma.

PMID- 15743007
TI  - Valid symptom reporting at upper endoscopy in a random sample of the Swedish
      adult general population: the Kalixanda study.
AB  - BACKGROUND: Upper oesophagogastroduodenoscopy is considered to be the gold
      standard for upper gastrointestinal disease assessment, but is currently seldom
      used in epidemiological studies. One concern is that the procedure may bias
      sampling among volunteers in a general adult population. The aim of this study
      was to explore whether the procedure affects symptom reporting. METHODS: A random
      sample of 3000 adults aged 20-81 years (mean age 50.4), from two Swedish
      municipalities (n=21,610) was surveyed using a validated postal questionnaire
      (the Abdominal Symptom Questionnaire) assessing gastrointestinal symptoms. A
      subsample of the responders was invited, in random order, to undergo an upper
      endoscopy and repeated symptom reporting using the same questionnaire, as well as
      a serology test for Helicobacter pylori. RESULTS: The response rate to the
      initial questionnaire was 74.2% and the participation rate for those eligible for
      the upper endoscopy was 73.3% (n = 1001, mean age 54.0 years, 48.8% male). No
      major social or symptom sampling error was encountered from the selection
      process, with the exception of an excess of symptom reporters among the youngest
      subjects. The prevalence of reflux symptoms, dyspeptic symptoms and irritable
      bowel symptoms was 40%, 37.6% and 29.6%, respectively, which is relatively high,
      but in no way extreme. CONCLUSIONS: The upper endoscopy survey strategy was
      successful. The response rate was high and there was no major selection bias of
      clinical relevance. The cohort selected for this study appears to be
      representative of the general Swedish adult population.

PMID- 15743008
TI  - Open-access gastroscopy in primary health-care offices to prevent peptic ulcer
      related hospitalization and mortality.
AB  - BACKGROUND: Open-access gastroscopy performed by general practitioners is
      available at some primary care health centres in our Central Finland hospital
      referral area. The aim of the present study was to examine whether this practice
      influences peptic ulcer-related hospitalization and mortality. METHODS: Data on
      peptic ulcer-related hospitalization were obtained from discharge registries of
      the hospitals. Cause of death statistics were obtained from Statistics Finland
      Bureau. RESULTS: In 1996--2001, 896 inhabitants living in our hospital referral
      area were hospitalized owing to peptic ulcer. Of these, 265 (29.6%) had an ulcer
      related to the use of aspirin (ASA) or non-steroidal anti-inflammatory drugs
      (NSAIDs). Among the hospitalized patients, mortality was 11.6% (n = 104). In
      municipalities with or without an open-access gastroscopy service, the rates of
      hospitalization were 49.1 cases/100,000/year (95% CI 44.8-53.4) versus 77.5
      cases/100,000/year (95% CI 72.0-83.0), and ulcer-related mortality 5.6
      cases/100,000/year (95% CI 4.1-7.1) versus 9.4/100,000/year (95% CI 7.5-11.3). In
      municipalities without the service, inhabitants were older and their overall
      morbidity and mortality higher than in municipalities offering open-access
      gastroscopy. Of patients under 75 years of age (n = 582), 48 (8.2%) died,
      compared with 56 (17.8%, P < 0.001) of patients aged 75 years or older (n = 314).
      Age was the only independent risk factor for death (odds ratio (OR) 1.03 per year
      (95% CI 1.02-1.05)). Among patients with ASA-NSAID-related ulcer, open-access
      endoscopy was protective against ulcer-related death (OR 0.17 (95% CI 0.03
      0.85)). CONCLUSIONS: Open-access gastroscopy in primary health-care offices
      significantly reduces ASA-NSAID-related ulcer mortality and may also reduce
      overall ulcer-related hospitalizations. The present results may, however, be
      biased by demographic factors. Age is a risk factor for death during ulcer
      related hospitalization.

PMID- 15743009
TI  - Small-bowel barium follow-through is rarely required in patients with a normal
      ileoscopy and terminal ileal biopsy and a normal or unremarkable colonoscopy.
AB  - BACKGROUND: There is an increase of reliance on ileoscopy in preference to small
      bowel barium follow-through in the diagnosis of terminal ileal Crohn disease. In
      this study the role of small-bowel barium follow-through after a normal or
      unremarkable ileocolonoscopy was investigated. METHODS: A retrospective analysis
      of all patients who had a colonoscopy followed by a small-bowel barium follow
      through over a 7-year period was performed. Patients with a previously
      established diagnosis of inflammatory bowel disease and those who had
      colonoscopic evidence of inflammatory bowel disease were excluded. RESULTS: Of
      the 96 patients who had a normal ileoscopy and normal or unremarkable
      colonoscopy, 3 had abnormalities detected at small-bowel barium follow-through.
      Two patients had abnormal terminal ileal biopsies, although the terminal ileum
      appeared macroscopically normal. The small-bowel barium follow-through helped to
      establish the diagnosis of Crohn disease. The other patient presented changes
      consistent with a previously established diagnosis. Of the 47 patients who had a
      normal or unremarkable total colonoscopy without ileoscopy, I had abnormalities
      detected at small-bowel barium follow-through consistent with a previously
      established diagnosis. CONCLUSIONS: Small-bowel barium follow-through is rarely
      required in patients who have had a normal ileoscopy and terminal ileum biopsy
      and a normal or unremarkable colonoscopy. It should only be performed if there is
      a very high index of suspicion of small-bowel pathology. In patients with
      suspected Crohn disease, it is important to take terminal ileum biopsies even if
      the ileum appears macroscopically normal at ileoscopy.

PMID- 15743010
TI  - Endoluminal gastroplication: what are the predictors of outcome?
AB  - BACKGROUND: Endoluminal gastroplication (EndoCinch) has emerged as an endoscopic
      anti-reflux therapy, but predictive factors for symptom relief have not been
      established. The aim of this study was to evaluate the major determinants to
      predict outcome in patients treated with EndoCinch. METHODS: A total of 53
      consecutive patients, treated with EndoCinch at a single center were included in
      this prospective study. Inclusion criteria were symptoms of chronic heartburn,
      dependency on proton-pump inhibitors, documented pathological esophageal acid
      exposure, and a hiatal hernia smaller than 3 cm in length. All patients underwent
      endoscopy, 24-h pH monitoring, esophageal manometry, barium esophagram, and a
      detailed questionnaire regarding their symptoms before treatment. Patients were
      stratified into a responder and a non-responder group using a questionnaire at 3
      month follow-up. A multivariate analysis was performed. RESULTS: The success rate
      was 64% (34/53 patients). Three variables weresignificantly predictive for
      successful endoscopic anti-reflux treatment at the multivariate level: presence
      of typical symptoms (P=0.01), complete symptom relief with acid suppressive
      therapy (P=0.01), and normal lower esophageal sphincter pressure (P = 0.04). Not
      predictive of outcome were age, body mass index, esophagitis, other manometric
      findings, hiatal hernia size, or pathological level of pH <4/24 h. Barium
      esophagram did not add any additional predictive information. CONCLUSIONS: Since
      no single factor can predict outcome after EndoCinch, a careful patient selection
      is mandatory to maximize the success rate. The ideal candidate for EndoCinch is a
      gastroesophageal (GERD) patient with a normal lower esophageal sphincter
      pressure, whose typical symptoms completely resolved with acid suppressive
      therapy.

PMID- 15743011
TI  - Severe heart disease in coeliac sprue and inflammatory Bowel disease: a common
      pathogenesis?

PMID- 15743012
TI  - Primary AL-amyloidosis, ulcerative colitis and collagenous colitis in a 57-year
      old woman: a case study.
AB  - A 57-year-old woman with AL-amyloid deposits in the heart, gastrointestinal tract
      and the liver developed ulcerative colitis, which was treated with
      glucocorticosteroids and 5-aminosalicylic acid, with good response. The AL
      amyloidosis was successfully treated with high-dose chemotherapy and autologous
      stem-cell transplantation. The patient was in good clinical condition for 18
      months after treatment, until she developed diarrhea, which was found to be due
      to collagenous colitis. Two years after treatment of amyloidosis, the patient is
      in excellent condition, the symptoms of heart failure have stabilized and no
      adverse effects of the treatment regime have been observed. The bowel diseases
      are in clinical remission.

PMID- 15743013
TI  - Exercise-related abdominal pain as a manifestation of the median arcuate ligament
      syndrome.
AB  - Abdominal pain related to exercise, often loosely referred to as 'stitch', is not
      uncommon, particularly among participants in sports that involve running. The
      cause of this typically transient pain is poorly understood with several
      aetiologies proposed including diaphragmatic ischaemia (1, 2). Other
      gastrointestinal symptoms that are common during prolonged or high-intensity
      exercise include nausea, diarrhoea and gastrointestinal bleeding (3, 4). These
      symptoms are also usually transient and are thought to protect against critical
      organ damage by promoting cessation of exercise. Decreased gastrointestinal blood
      flow, increased motility and altered neuroendocrine modulation are postulated
      disease mechanisms (3). We report here a case of an elite runner with exercise
      related severe abdominal pain and diarrhoea related to compression of the coeliac
      axis by the median arcuate ligament. Complete symptom relief was achieved with
      surgical division of the constricting ligament. The clinical characteristics and
      pathogenesis of coeliac axis compression syndrome are discussed.

PMID- 15743014
TI  - Risk of extra-oesophageal malignancies in Barrett's oesophagus.

PMID- 15743015
TI  - Improved technologies enhance the efficacy of food iron fortification.

PMID- 15743017
TI  - Enhancers of iron absorption: ascorbic acid and other organic acids.
AB  - Ascorbic acid (AA), with its reducing and chelating properties, is the most
      efficient enhancer of non-heme iron absorption when its stability in the food
      vehicle is ensured. The number of studies investigating the effect of AA on
      ferrous sulfate absorption far outweighs that of other iron fortificants. The
      promotion of iron absorption in the presence of AA is more pronounced in meals
      containing inhibitors of iron absorption. Meals containing low to medium levels
      of inhibitors require the addition of AA at a molar ratio of 2:1 (e.g., 20 mg AA:
      3 mg iron). To promote absorption in the presence of high levels of inhibitors,
      AA needs to be added at a molar ratio in excess of 4:1, which may be impractical.
      The effectiveness of AA in promoting absorption from less soluble compounds, such
      as ferrous fumarate and elemental iron, requires further investigation. The
      instability of AA during food processing, storage, and cooking, and the
      possibility of unwanted sensory changes limits the number of suitable food
      vehicles for AA, whether used as vitamin fortificant or as an iron enhancer.
      Suitable vehicles include dry-blended foods, such as complementary, precooked
      cereal-based infant foods, powdered milk, and other dry beverage products made
      for reconstitution that are packaged, stored, and prepared in a way that
      maximizes retention of this vitamin. The consumption of natural sources of
      Vitamin C (fruits and vegetables) with iron-fortified dry blended foods is also
      recommended. Encapsulation can mitigate some of the AA losses during processing
      and storage, but these interventions will also add cost. In addition, the
      bioavailability of encapsulated iron in the presence/absence of AA will need
      careful assessment in human clinical trials. The long-term effect of high AA
      intake on iron status may be less than predicted from single meal studies. The
      hypothesis that an overall increase of dietary AA intake, or fortification of
      some foods commonly consumed with the main meal with AA alone, may be as
      effective as the fortification of the same food vehicle with AA and iron, merits
      further investigation. This must involve the consideration of practicalities of
      implementation. To date, programs based on iron and AA fortification of infant
      formulas and cow's milk provide the strongest evidence for the efficacy of AA
      fortification. Present results suggest that the effect of organic acids, as
      measured by in vitro and in vivo methods, is dependent on the source of iron, the
      type and concentration of organic acid, pH, processing methods, and the food
      matrix. The iron absorption-enhancing effect of AA is more potent than that of
      other organic acids due to its ability to reduce ferric to ferrous iron. Based on
      the limited data available, other organic acids may only be effective at ratios
      of acid to iron in excess of 100 molar. This would translate into the minimum
      presence/addition of 1 g citric acid to a meal containing 3 mg iron. Further
      characterization of the effectiveness of various organic acids in promoting iron
      absorption is required, in particular with respect to the optimal molar ratio of
      organic acid to iron, and associated feasibility for food application purposes.
      The suggested amount of any organic acid required to produce a nutritional
      benefit will result in unwanted organoleptic changes in most foods, thus limiting
      its application to a small number of food vehicles (e.g., condiments, beverages).
      However, fermented foods that already contain high levels of organic acid may be
      suitable iron fortification vehicles.

PMID- 15743016
TI  - Enhancing the absorption of fortification iron. A SUSTAIN Task Force report.
AB  - Iron deficiency remains a major global health problem affecting an estimated 2
      billion people. The World Health Organization ranked it as the seventh most
      important preventable risk for disease, disability, and death in 2002. Since an
      important factor in its causation is the poor bioavailability of iron in the
      cereal-based diets of many developing countries, SUSTAIN set up a Task Force,
      consisting of nutritional, medical, industry, and government experts to consider
      strategies for enhancing the absorption of fortification iron. This paper
      summarizes the findings of this Task Force. Detailed reviews of each strategy
      follow this overview. Highly soluble compounds of iron like ferrous sulfate are
      desirable food fortificants but cannot be used in many food vehicles because of
      sensory issues. Thus, potentially less well-absorbed forms of iron commonly are
      used in food fortification. The bioavailability of iron fortificants can,
      however, be enhanced with innovative ingredient technologies. Ascorbic acid,
      NaFeEDTA, ferrous bisglycinate, and dephytinization all enhance the absorption of
      fortification iron, but add to the overall costs of fortification. While all
      strategies cannot be recommended for all food fortification vehicles, individual
      strategies can be recommended for specific foods. For example, the addition of
      ascorbic acid is appropriate for dry blended foods such as infant foods and other
      dry products made for reconstitution that are packaged, stored, and prepared in a
      way that maximizes retention of this vitamin. NaFeEDTA can be recommended for
      fortification of fish sauce and soy sauce, whereas amino acid chelates may be
      more useful in milk products and beverages. With further development,
      dephytinization may be possible for low-cost, cereal-based complementary foods in
      developing countries. Encapsulation of iron salts in lipid coatings, while not an
      iron absorption-enhancing strategy per se, can prevent soluble forms of iron from
      interacting undesirably with some food vehicles and hence broaden the application
      of some fortificants. Research relevant to each of these strategies for enhancing
      the bioavailability or utility of iron food fortificants is reviewed. Individual
      strategies are evaluated in terms of enhancing effect and stability, organoleptic
      qualities, cost, and regulatory issues of interest to the nutrition community,
      industry, and consumers. Recommendations are made on potential usages and further
      research needs. Effective fortification depends on the selection of technically
      feasible and efficacious strategies. Once suitable strategies have been
      identified, cost becomes very important in selecting the best approach to
      implement. However it is essential to calculate cost in relation to the amount of
      bioavailable iron delivered. An approach to the calculation of cost using a
      conservative estimate of the enhancing effects of the innovative technologies
      discussed in the supplement is given in the final section.

PMID- 15743018
TI  - The potential role of NaFeEDTA as an iron fortificant.
AB  - Ethylene diamine tetraacetic acid (EDTA) is a hexadentate chelator, which can
      combine with virtually every metal in the periodic table. CaNa2EDTA and Na2EDTA
      (ADI 2.5 mg EDTA/kg body weight/day) are widely used as sequestering agents in
      canned products, while NaFeEDTA is a promising iron fortificant. Binding of EDTA
      with iron is favored in the acid milieu of the stomach, irrespective of whether
      the EDTA is administered as CaNa2EDTA, Na2EDTA, or NaFeEDTA, but in the more
      alkaline medium of the duodenum the iron is exchanged, in part, with other
      metals. The iron released from EDTA is absorbed by the normal physiological
      mechanisms. When NaFeEDTA is present in a meal, the iron moiety exchanges with
      the intrinsic food iron and the EDTA partially protects the iron in this common
      non-heme iron pool from the effects of inhibitors of iron absorption, such as
      phytates and polyphenols. When iron is added as NaFeEDTA to an inhibitory meal,
      it is two to three times better absorbed than is iron added as ferrous sulfate.
      It also has a similar effect on the intrinsic food iron in the meal.
      Fortification with NaFeEDTA is most efficacious when administered with cereal-
      and legume-based diets but offers no advantages over other fortificants when
      added to meals of high bioavailability. Its potential as a fortificant has been
      confirmed in five extended fortification trials carried out in developing
      countries. There is no evidence that NaFeEDTA in the dose range proposed for food
      fortificants (5 to 10 mg iron daily) will have any direct toxic effects. Na2EDTA
      and CaNa2EDTA have proved safe over a number of years, while the Joint FAO/WHO
      Expert Committee on Food Additives concluded in 1999 that NaFeEDTA "could be
      considered safe when used in supervised fortification programs". Animal and human
      studies, including the results of two fortification trials, suggest that NaFeEDTA
      has little or no effect on overall zinc metabolism. Indeed, if anything, it
      increases zinc and possibly copper absorption. Data on potentially toxic metals,
      such as lead mercury, aluminum, and manganese, are limited but the evidence that
      is available is uniformly negative thus far. Further studies in this field are
      desirable. The long-term potential of NaFeEDTA fortification to cause iron
      overload is conjectural but the available evidence suggests that homeostatic
      controls would prevent excess iron accumulation in the normal population.
      NaFeEDTA, which is pale yellow in color, causes fewer organoleptic changes in a
      number of stored vehicles, including cereals, than do other soluble iron salts.
      Other potential vehicles include condiments, several of which have been
      successfully used in fortification trials. What is currently lacking is a
      consolidated body of published evidence on the stability of NaFeEDTA during
      processing, storage, and household cooking in widely consumed food vehicles,
      coupled with standardized testing of consumer acceptance of each fortified
      vehicle. While NaFeEDTA seems to be an appropriate fortificant for developing
      countries, its cost is about six to eight times that of ferrous sulfate in terms
      of equivalent amounts of iron. Its better absorption (a factor of 2-3) might make
      it possible to halve the daily fortification level but, it still remains
      expensive and there is a pressing need for food grade NaFeEDTA at more affordable
      prices. Another possible option is the use of other salts of EDTA (Na2EDTA or Ca
      Na2EDTA) together with a soluble source of iron, such as ferrous sulfate. The
      combination has been shown to be as effective as NaFeEDTA when the EDTA:Fe molar
      ratio is between 1:2 and 1:1. This approach is, however, only feasible with
      vehicles that are stored for short periods because of ferrous sulfate's
      propensity to cause organoleptic changes. The search for an iron source that is
      more stable but at the same time available to combine with EDTA has been
      unsuccessful thus far. Target populations for fortification with NaFeEDTA include
      all those that subsist on cereal- and legume-based diets, with the most
      appropriate vehicles being cereal products and condiments. The fortification of
      infant milk and cereal formulas with NaFeEDTA does not seem appropriate, since
      the amounts of NaFeEDTA required for effective fortification would be close to
      the acceptable daily intake (ADI) of 2.5 mg EDTA/kg body weight/day.

PMID- 15743019
TI  - Iron amino acid chelates.
AB  - Iron amino acid chelates, such as iron glycinate chelates, have been developed to
      be used as food fortificants and therapeutic agents in the prevention and
      treatment of iron deficiency anemia. Ferrous bis-glycine chelate (FeBC), ferric
      tris-glycine chelate, ferric glycinate, and ferrous bis-glycinate hydrochloride
      are available commercially. FeBC is the most studied and used form. Iron
      absorption from FeBC is affected by enhancers and inhibitors of iron absorption,
      but to a lesser extent than ferrous sulfate. Its absorption is regulated by iron
      stores. FeBC is better absorbed from milk, wheat, whole maize flour, and
      precooked corn flour than is ferrous sulfate. Supplementation trials have
      demonstrated that FeBC is efficacious in treating iron deficiency anemia.
      Consumption of FeBC-fortified liquid milk, dairy products, wheat rolls, and multi
      nutrient beverages is associated with an improvement of iron status. The main
      limitations to the widespread use of FeBC in national fortification programs are
      the cost and the potential for promoting organoleptic changes in some food
      matrices. Additional research is required to establish the bioavailability of
      FeBC in different food matrices. Other amino acid chelates should also be
      evaluated. Finally there is an urgent need for more rigorous efficacy trials
      designed to define the relative merits of amino acid chelates when compared with
      bioavailable iron salts such as ferrous sulfate and ferrous fumarate and to
      determine appropriate fortification levels

PMID- 15743020
TI  - Phytic acid degradation as a means of improving iron absorption.
AB  - Phytic acid is a potent inhibitor of native and fortification iron absorption and
      low absorption of iron from cereal- and/or legume-based complementary foods is a
      major factor in the etiology of iron deficiency in infants. Dephytinization of
      complementary foods or soy-based infant formulas is technically possible but, as
      phytic acid is strongly inhibitory at low concentrations, complete enzymatic
      degradation is recommended. If this is not possible, the phytic acid to iron
      molar ratio should be decreased to below 1:1 and preferably below 0.4:1. Complete
      dephytinization of cereal- and legume-based complementary foods has been shown to
      increase the percentage of iron absorption by as much as 12-fold (0.99% to
      11.54%) in a single-meal study when the foods were reconstituted with water. The
      addition of milk, however, inhibits iron absorption and overcomes the enhancing
      effect of phytic acid degradation. Dephytinization can therefore be strongly
      recommended only for cereal/legume mixtures reconstituted with water, especially
      low-cost complementary foods destined for infants in developing countries. In
      countries where infant cereals are consumed with milk, ascorbic acid addition can
      more easily be used to overcome the negative effect of phytic acid on iron
      absorption. Similarly with soy-based infant formulas, especially if manufactured
      from low-phytate isolates, ascorbic acid can be used to ensure adequate iron
      absorption.

PMID- 15743021
TI  - The potential of encapsulated iron compounds in food fortification: a review.
AB  - Iron (Fe) encapsulation has the potential to help overcome several major
      challenges in Fe fortification of foods. It may decrease unwanted sensory changes
      in fortified products and reduce interactions of Fe with food components that
      lower Fe bioavailability. However, the effect of encapsulation per se on Fe
      bioavailability is a concern. Rat studies comparing encapsulated ferrous sulfate,
      ferric ammonium citrate, and ferrous fumarate to non-encapsulated compounds
      indicate that a ratio of capsule:substrate of > or = 60:40 may decrease the
      relative bioavailability (RBV) of the Fe by approximately 20%. At a ratio of
      capsule:substrate of < or = 50:50, the RBV of encapsulated ferrous sulfate
      appears to be similar to ferrous sulfate. Even minor changes in capsule
      composition may influence Fe bioavailability. Encapsulated ferrous fumarate given
      with ascorbic acid as a complementary food supplement and encapsulated ferrous
      sulfate fortified into salt have been shown to be efficacious in anemic children.
      For salt fortification, further refinements in Fe capsule design are needed to
      increase resistance to moisture and abrasion, while maintaining bioavailability.
      Studies evaluating the potential efficacy of encapsulated Fe in staple cereals
      (wheat and maize flours) are needed. A potential barrier to use of encapsulated
      forms of Fe in staple food fortification is the relatively low melting point of
      the capsules, which may cause unwanted sensory changes during food preparation.
      Research and development efforts to improve the quality of coatings and their
      resistance to high temperatures are ongoing. Process costs for encapsulation can
      be high, and unless they can be reduced, may limit applications. Further research
      is needed to determine which encapsulation technologies are most effective in
      ensuring iron bioavailability from encapsulated compounds.

PMID- 15743022
TI  - A model for calculating the cost of employing iron absorption enhancement
      strategies in fortification programs.

PMID- 15743023
TI  - Somatostatin receptor expression in vivo and response to somatostatin analog
      therapy with or without other antineoplastic treatments in advanced medullary
      thyroid carcinoma.
AB  - The long-term treatment of metastatic medullary thyroid carcinoma (MTC) with
      somatostatin (SST) analogs was evaluated in 22 patients with persistant or
      relapsed disease and with in vivo positive SST receptor (SSTR) tumors. After
      surgical intervention all patients but one, initially or at a later time, had
      persistenly (15) or after relapse (7) elevated serum calcitonin (CT, 252-69482
      pg/ml) and carcinoembryonic antigen (CEA, 8-1130 ng/ml) concentrations; also, all
      of them showed positive uptake in 111In-pentetreotide scanning. Daily doses of
      0.4-1.0 mg octreotide subcutaneously, or monthly doses of 20-30 mg long-acting
      octreotide (LAR) intramuscularly for 3-21 months were administered. Systemic
      chemotherapy (Ch) with or without external radiotherapy (eRT) was given to 13
      patients simultaneously. A beneficial effect on pre-existing diarrhea was
      observed in 8 patients (subjective partial remmission, sPR 36.4%); 10 other
      patients showed stable disease, while in 4 a worsening of pre-existing diarrhea
      was observed. CT and CEA concentrations decreased more than 25% in 4 out of 22
      patients (18%) and 11 patients showed a decrease of less than 25% (biological
      SD). No objective response in tumour growth was demonstrated. Patients (10
      survivors in group B) treated with Ch+eRT plus Octerotide showed higher sR
      (92.5%), lower mortality (23.1%), longer mean time to death (130 months) and
      longer mean total survival (mts) time (145 months) in comparison to group A
      patients who had 66.7% sR, 33.3% mortality, only 88.5 months mean time to death
      and 101 months mts-time. Long-term octreotide and octreotide-LAR treatment offers
      a subjective and biological partial remission in one third and in one fourth of
      the MTC patients respectively, but it does not improve the natural course of the
      tumor. It remains to be answered if these drugs, combined with other
      antineoplastic therapies, have a synergistic effect relating to treatment
      response and to patient survival and mortality.

PMID- 15743024
TI  - Presence of HPV in head and neck tumours: high prevalence in tonsillar
      localization.
AB  - Human papillomavirus (HPV) seems to be involved in head and neck carcinogenesis.
      To investigate this association, viral presence and expression were analysed by
      polymerase chain reaction (PCR)-based methods and correlated to tumour
      localization, clinical-pathological aspects, and alcohol and tobacco exposure in
      65 patients. HPV DNA was found in 16 cases (24.6%); the HPV types detected were:
      HPV16 (10 cases), HPV 6 (3 cases) HPV 33, 35, and 58 (one case each). The tonsil
      was the location with the highest HPV positivity (6/8, 75%). This percentage was
      significantly higher than that found in tumours from any other site (P<0.01).
      Viral transcripts of early regions were detected in all HPV16 positive tumours.
      HPV status was not related to age, gender, tumour stage or grade, and use of
      alcohol and/or tobacco. The results suggest that HPV16 is actively involved in
      the genesis of a subset of head and neck cancers and that the tonsillar
      localization may be considered a hot spot for viral transformation.

PMID- 15743025
TI  - Identification of sentinel node in breast cancer: comparison between peritumoral
      and periareolar injection of the radiopharmaceutical contrast medium.
AB  - Axillary node status is the most important prognostic factor for patients with
      primary breast carcinoma. The sentinel node biopsy (SN) technique has received
      much attention as a possible alternative to axillary lymph node dissection. The
      aim of this study is to identify the sentinel node by periareolar and subdermal
      injection of the radiopharmaceutical in four points, independent of tumor
      topography and the presence of biopsies and/or previous surgery. The peritumoral
      injection technique was carried out for comparison purposes. This study was
      performed on 115 patients, divided into 2 groups: Group A (25 patients,
      peritumoral injection) and Group B (90 patients, injection in four points). All
      the SN biopsies were studied by both imprint cytology and H&E staining. Control
      axillary lymph-node dissection was followed in all patients from Group A and in
      these positive cases from Group B. Twenty-two out of the twenty-five (88%) SNs
      were identified in Group A. There was no false negative; the sensitivity and
      specificity were 100%. Eighty-two of the ninety (91.1%) SNs were identified in
      Group B. Lymphoscintigraphy showed radiopharmaceutical migration to axilla in
      93.7% of the cases. Hotspot area was 10 to 100 times the intensity of the
      background radiation. Among the 92 cases with negative sentinel nodes at
      intraoperative examination (TP), the SN histopathology confirmed the absence of
      cancer cells in 89 patients, whereas 3 were positive for metastatic cells. This
      study shows that periareolar injection in four points seems to be a good
      lymphatic mapping method for SN identification. We suggest standardizing this
      site of injection to identify the SNs. More studies to confirm these findings are
      ongoing.

PMID- 15743026
TI  - Adjuvant therapy of melanoma patients (stage II, III): a pilot immuno
      toxicological study.
AB  - A pilot study was conducted to assess the tolerability and the effect on host
      immunity of a post-surgery adjuvant treatment of melanoma patients with an anti
      angiogenic agent, Tamoxifen (TAM, 20 mg/die p.o., daily), combined with
      immunomodulating cytokines, i.e. recombinant interleukin-2 (IL-2, 4 MUI/m2 s.c.,
      day 8,10,12) and alpha-2b-interferon (IFN, 3 MUI/m2 i.m., day 15,17,19), starting
      a new cycle on day 21, for a total of 12 cycles. Fifty patients (pts) entered
      into the study, 27 males and 23 females with a median age of 55 years (range 25
      75), performance status (ECOG) 0 with melanoma stage IIA (12 patients), stage IIB
      (28 patients), stage III (10 patients). Preliminary in vitro studies showed that
      TAM does not interfere with up-regulation of natural immunity induced by IFN, IL
      2, or IFN + IL-2 in normal peripheral blood mononuclear cells (MNC). The clinical
      study indicates that the protocol was well tolerated. Increase of NK and LAK
      activity of patient MNC was observed on day 15. The mean disease-free interval
      was 10 months and 40 pts were alive at 5 years of follow-up. Further
      investigations should be performed to test effectiveness of this protocol in a
      randomized study.

PMID- 15743027
TI  - Renal tubular dysfunction and urinary zinc excretion in breast cancer patients
      treated with anthracycline-based combination chemotherapy.
AB  - The survival of breast cancer patients has significantly improved through the
      treatment with anthracyclines. Although anthracyclines are known to produce renal
      disease in experimental animals, little is known about the toxicity of
      anthracyclines at clinically relevant doses in humans. In a previous study on
      cancer patients we have observed an increase in the urinary activity of N-acetyl
      beta-D-glucosaminidase (NAG), an indicator of renal tubular cell dysfunction that
      was accompanied by increased urinary zinc loss. Because an increase in NAG
      activity was reported after the treatment with anthracyclines, we hypothesized
      that an increase in urinary NAG activity in breast cancer patients treated with
      anthracycline-based regimens will be accompanied by hyperzincuria and
      hypozincemia. Urinary and serum zinc, urinary NAG and serum creatinine were
      examined during chemotherapy in 26 breast cancer patients treated with
      anthracycline-based chemotherapy. A trend for increased NAG activity, as compared
      to baseline, was observed throughout the first 4 cycles of treatment. NAG
      activity was significantly elevated compared to pretreatment levels one week
      after the first, third and fourth dose of chemotherapy. Serum creatinine
      concentrations decreased significantly after the second cycle of therapy. On the
      other hand, urinary and serum zinc levels did not change significantly during the
      treatment. In conclusion, our data confirm the presence of mild renal tubular
      cell dysfunction in breast cancer patients treated with doxorubicin-based
      chemotherapy. Increased urinary NAG is accompanied by a decrease in serum
      creatinine which is consistent with hyperfiltration. These changes are not
      associated with abnormalities of renal zinc handling or a decrease in serum zinc
      concentrations.

PMID- 15743028
TI  - The role of Echo Colour/Power Doppler and magnetic resonance in expansive parotid
      lesions.
AB  - The purpose of this research was to evaluate the role of Echo Colour/Power
      Doppler and Magnetic Resonance Imaging (MRI) in the diagnosis of expansive
      parotid lesions, and to establish criteria for differential diagnosis between
      benign and malignant forms. Forty nine patients (23 males and 26 females), aging
      from 30 to 85 years, with an expansive pathology of parotid gland were enrolled
      in our study from February 1999 through August 2004. Each patient was carefully
      assessed employing both ultrasonography integrated with Color/Power Doppler and
      MRI. Eventually, all patients received echo-guided needle-biopsy and surgical
      excision of the parotid lesion. Preliminary ultrasound assessed site, size,
      echoic appearance and margins of the lesion. In order to assess blood supply by
      means of Colour/Power Doppler, we divided the patients in four groups. Our MRI
      diagnostic criteria included site, size, intensity of signal, behaviour of the
      lesion after i.v. contrast, relationship with facial nerve and retromandibular
      vein, detection of margins and proximity to adjacent structures. On the basis of
      our results, the Authors concluded that both Echo Colour/Power Doppler and MRI
      play a very important role in the diagnosis and surgical planning of parotid
      gland lesions.

PMID- 15743029
TI  - High risk of gallbladder carcinoma in elderly patients with segmental
      adenomyomatosis of the gallbladder.
AB  - The clinical significance of adenomyomatosis of the gallbladder remains unclear.
      This study aimed to clarify the relationship between segmental adenomyomatosis
      and gallbladder carcinoma, and to elucidate the histogenesis of gallbladder
      carcinoma associated with segmental adenomyomatosis. A total of 4,560 consecutive
      patients underwent cholecystectomy. The specimens were examined grossly and
      histologically. Adenomyomatosis of the gallbladder was divided into segmental,
      fundal, and diffuse types. Sixty noncancerous gallbladders with segmental
      adenomyomatosis were examined for epithelial metaplasia. The incidence of
      gallbladder carcinoma was higher in patients with segmental adenomyomatosis
      (22/334, 6.6%) than in those without (181/4226, 4.3%; P=0.049). This difference
      was more marked among patients equal to or older than 60 years of age
      (15/96,15.6% versus 147/2407, 6.1%, respectively; P<0.001). The other types of
      adenomyomatosis did not show any significant increases in the incidence of
      gallbladder carcinoma. In all 22 patients with both segmental adenomyomatosis and
      carcinoma, the tumors developed only in the fundal mucosa. Epithelial metaplasia
      was more marked in the fundal mucosa of segmental adenomyomatosis than in the
      neck mucosa (P=0.003). Segmental adenomyomatosis is a high-risk condition for
      gallbladder carcinoma, especially in elderly patients. Epithelial metaplasia
      appears to be related to increased carcinogenesis in the fundal mucosa of
      segmental adenomyomatosis.

PMID- 15743030
TI  - A MEK inhibitor (U0126) markedly inhibits direct liver invasion of orthotopically
      inoculated human gallbladder cancer cells in nude mice.
AB  - Primary cancer of the gallbladder is not unusual. Most cases of gallbladder
      cancer are found at an advanced stage, accompanied by the invasion to the liver,
      metastases to the lymph nodes and distant organs, and peritoneal dissemination.
      In this study, we first examined the effect of mitogen-activated protein kinase
      kinase (MEK) inhibitors on the production of matrix metalloproteinases (MMPs),
      urokinase-type plasminogen activator (uPA), and tissue inhibitors of
      metalloproteinases (TIMPs) in a human gallbladder cancer cell line, NOZ cells in
      vitro. MEK inhibitors (PD98059 and U0126) inhibited the production of MMP-2, MMP
      9 and high MW uPA, and upregulated TIMPs (TIMP-1, TIMP-2 and TIMP-3).
      Subsequently, we examined the effect of U0126 on invasion and metastasis of
      orthotopically inoculated NOZ cells in nude mice. Direct liver invasion by cancer
      cells was detected in all of the mice in the control group, but in only one mouse
      in the U0126-treated group. Most of the primary tumors in the U0126-treated group
      expanded to the liver, but did not invade into the liver. Vessel invasion in the
      liver was evident in 4 out of 5 mice in the control group, but in only one mouse
      in the U0126-treated group. Lymph node metastases and peritoneal dissemination
      were recognized in all of the mice in both groups. All 5 mice in the U0126
      treated group, and 4 out of 5 mice in the vehicle control group, had metastases
      in the lungs. The present results suggest that a MEK inhibitor, U0126, prolonged
      the survival of the mice with NOZ tumor by inhibiting direct liver invasion and
      vessel invasion of the cancer cells via down-regulation of the matrix degrading
      ability of the cancer cells.

PMID- 15743031
TI  - Construction and selection of human anti-idiotypic antibody single chain variable
      fragments or CDR3 fragments of nasopharyngeal carcinoma.
AB  - Peripheral blood mononuclear cells (PBMCs) of patients with NPC were immunized in
      vitro by anti-NPC monoclonal antibody FC2 and transformed by Epstein-Barr virus
      (EBV). Detection showed that of 10 NPC patients, 8 patients' B cells immunized by
      FC2 and transformed by EBV produced anti-idiotypic antibodies to NPC. Five types
      of VH genes and 7 types of VL genes were obtained by RT-PCR amplification and
      then connected with (Gly4Ser)3 linker to form 14 types of scFv genes. ScFv genes
      digested with Sfi I were cloned into vector fUSE5 and transformed into E. coli MC
      1061. Phage anti-idiotypic antibody library with 1.5 x 10(8) clones was obtained.
      After four rounds of panning, 270 phage clones were selected randomly and 91 FC2
      positive clones were obtained by Sandwich ELISA, the positive ratio was 33.7%. 5
      clones (D83, E92, G22, I50, I54), which might display beta type Ab2 scFv, were
      selected by binding inhibition test. These 5 phage anti-idiotypic antibodies were
      further analyzed by DNA sequencing. The VDJ regions of G22, I50, I54 belonged to
      VH4-39-D4-11-JH3-linker-V1-19-JL2, VH4-4-D4-11-JH6 and VH4-31-D4-11-JH6,
      respectively. E92 had the same VDJ regions with G22; D83 had the same VDJ regions
      with 150. So, a strategy for preparing and selecting beta type Ab2 scFv or CDR by
      means of immunization in vitro, EBV transformation and phage display technique is
      feasible, which paves a way for preparing cancer vaccine using beta type Ab2
      scFv.

PMID- 15743032
TI  - Repeated administration of cytokines improve the ex-vivo generation of human
      dendritic cells.
AB  - The in vitro generation of dendritic cells (DCs) enables us to practice antitumor
      immune therapy. Peripheral monocytes can differentiate to DCs in the presence of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL
      4) in vitro. To generate a large number of DCs, we compared the number of DCs
      generated from leukapheresis products to those from conventional blood samplings
      in healthy volunteers. The induction rates of the DCs were equal for these two
      blood samplings, and 10(7) DCs were obtainable from one leukapheresis product. In
      contrast, the number of DCs varied significantly depending on the individual (30
      50% in good responders vs. less than 10% in poor responders). DCs appeared as
      aggregates of indented cells during culture in good responders, while large cells
      were floating sparsely in poor responders. Repeated administration of GM-CSF and
      IL-4 improved the yields of DCs and induced proliferation of autologous
      lymphocytes in poor responders. As a prototype of cell therapy, the generation of
      DCs will require a titration of differentiation processes, depending on each
      individual's responsiveness to cytokines.

PMID- 15743033
TI  - P21 and Bax expression in cutaneous malignant melanomas: correlation with
      histologic prognostic parameters.
AB  - In response to DNA damage, p53 accumulates and regulates expression of several
      genes, including cyclin-dependent kinase inhibitor p21. Cells then undergo p21
      dependent cell cycle arrest, which allows DNA damage repair and apoptosis. Bax is
      a death promoter member of the bcl-2 family which plays a central role in the
      regulation and commitment to programmed cell death. Breslow thickness is the most
      important factor in predicting prognosis for cutaneous malignant melanoma. In
      order to define the role of cyclin dependent kinase inhibitors and apoptosis
      regulators in invasion of malignant melanoma we investigated the expression of
      p21 and bax proteins. We observed that significant high p21 expression was
      associated with increasing Breslow thickness (Spearman correlation analysis,
      p=0.01). Additionally, Clark level I and II tumours expressed significantly lower
      p21 positivity than Clark level III, IV and V (p=0.006). Similarly, thick tumors
      showed a higher bax expression (p=0.012). Our results suggested that the role of
      p21 expression is more complicated in melanocytic skin cancers and abnormal
      regulation or abnormal function of cell cycle regulators occurred in the
      development and progression of malignant melanoma. In order to understand the
      role of bax expression in thick malignant melanomas and invasion biology,
      comparative analytic studies with other apoptosis regulators are needed.

PMID- 15743034
TI  - Detection of disseminated tumour cells as a potential surrogate-marker for
      monitoring palliative chemotherapy in colorectal cancer patients.
AB  - In a pilot study the effect of palliative chemotherapy on the detection rates of
      circulating tumour cells in peripheral venous blood of stage IV colorectal cancer
      patients was investigated. The results indicate a recruitment of tumour cells
      during chemotherapy and suggest a poorer survival for tumour cell positive
      patients. Circulating tumour cells have been shown to be a potential prognostic
      factor in patients who undergo curative resection for colorectal cancer. The
      effect of chemotherapy on the detection rates of disseminated tumour cells in
      blood has not yet been adequately investigated. Objective of this pilot-study was
      to analyze circulating tumour cells in peripheral venous blood of colorectal
      cancer patients undergoing chemotherapy in order to evaluate its potential value
      as a surrogate-marker for predicting clinical outcome after chemotherapy. Our
      hypothesis was that chemotherapy results in a reduction of the detection rates of
      circulating tumour cells in colorectal cancer patients. Forty-two Stage IV
      patients were examined at three different time points before and during
      palliative chemotherapy for the presence of disseminated tumour cells, using a
      previously described RT-PCR-assay for cytokeratin 20. 80.1% of the patients
      showed disseminated tumour cells at least once. Before chemotherapy, patients
      with multi-organ metastases were positive in 62.5%, patients with locally limited
      disease in only 14.3%. After the first chemotherapy, the detection rates in the
      latter group increased to 62.5%, for all patients in the same time from 46.3% to
      57.5%. Clinical therapy responders showed an increase in the detection rates from
      28.5% before to 71.4% after chemotherapy. In contrast, chemotherapy had no effect
      on tumour cell detection rates of patients with progressive disease (57% before
      vs. 60% after therapy). Patients with detected circulating tumour cells showed a
      shorter overall survival than patients without circulating tumour cells (83 vs.
      53 weeks). Clinical therapy responders on average lived only 3 weeks longer than
      non-responders. In contrast to the original hypothesis, our data suggest a
      recruiting of circulating tumour cells during chemotherapy in advanced colorectal
      cancer. Further investigations are needed to clarify the potential role of
      circulating tumour cells for monitoring chemotherapy in these patients.

PMID- 15743036
TI  - Genetic disregulation of gene coding tumor necrosis factor alpha receptors
      (TNFalpha Rs) in colorectal cancer cells.
AB  - The expression of TNF ligand by malignant cells might be a mechanism for tumour
      immune escape. Genetic disregulation of gene coding TNF receptors was observed in
      neoplastic disease by an increased number of receptors on tumour cells and ligand
      receptor activity. It might cause tumour proliferation and metastatic potential.
      Structure of TNF receptors influences TNF activity in vivo and structure of TNF
      R2 gene may suggest post-transcription modification based on alternative
      splicing. The aim of the study was to analyse the expression of gene coding TNF
      receptors R2 and R2/R7 (without exon 7) by estimation of mRNA expression of
      colorectal cancer cells in comparison with surrounding tissue free from
      neoplastic infiltration and searched for differently spliced TNFalphaR2/R7
      isoforms. The study included fifty four patients with histopathologically
      confirmed adenocarcinoma (Stage III according to the AJC TNM Classification).
      Tissue samples removed from the tumour region were obtained from colorectal
      cancer patients undergoing surgical treatment. The samples were divided into two
      parts. The first one--was routinely examined histopathologically, the second one-
      was used for RNA extraction and the number of TNF and its receptors mRNA copies
      were subsequently quantified. The TNF and TNFRII genes expression were estimated
      based on the number of mRNA copies on 1 microg total RNA. The presence of TNFR2
      and TNFR2/R7 isoforms in tumour, normal and metastatic cells was observed. The
      highest number of mRNA TNF copies and over expressed TNF genes were investigated
      and significantly noticed in metastatic cells (lymph nodes). The decreased number
      of TNFR2/R7 mRNA copies in metastatic lymph nodes secondarily influenced the
      decreased TNF soluble receptors' concentration. In conclusion, the genetic
      disregulation observed in neoplastic disease usually concerns dysfunction of
      cytokines receptor genes.

PMID- 15743035
TI  - Clinicopathological study of the expression of syndecan-1 in invasive breast
      carcinomas. correlation with extracellular matrix components.
AB  - Syndecan-1, a cell surface proteoglycan found predominantly on epithelia of
      mature tissues, binds both extracellular matrix (ECM) components and basic
      fibroblast growth factor (bFGF) and is implicated in the restriction of growth
      and invasiveness of neoplastic cells, as it induces the adhesion capacity of
      neoplastic cells with the stroma. In this study we investigated breast carcinomas
      for the immunohistochemical expression of syndecan-1 protein and these results
      were assessed in relation to clinicopathological parameters, in order to clarify
      its prognostic value. The possible relationship with hormone receptors content,
      p53, cell proliferation markers, and extracellular matrix components was also
      estimated. Tissue sections from 102 breast carcinomas were used and
      immunostainings were performed on formalin-fixed, paraffin-embedded tissue
      sections by the labelled streptavidin avidin biotin (LSAB) method. High
      expression levels were observed, as 75/102 (73.5%) cases expressed
      immunoreactivity in more than 80% of neoplastic cells, while 67/102 (65.7%)
      exhibited high staining intensity. The survival analysis showed an increased
      mortality risk associated with high syndecan-1 staining intensity with borderline
      significance (p=0.041). In addition, there was a strong negative correlation
      between syndecan-1 protein expression and ECM, specifically collagen IV (p=0.026)
      and tenascin (p=0.0067). The results of the present study show the implication of
      this protein in the remodeling of breast cancer tissue, through the interaction
      with other extracellular matrix components, probably influences the tumour
      progression.

PMID- 15743038
TI  - An association between the Trp64Arg polymorphism in the beta3-adrenergic receptor
      gene and endometrial cancer and obesity.
AB  - Beta3-adrenergic receptor (beta3AR) stimulates lipolysis in human fat cells, so
      its gene can constitute a candidate to explain a part of genetic predisposition
      to human obesity and related disorders. The Trp64Arg polymorphism in the beta3AR
      gene has been reported to be associated with insulin resistance, obesity and type
      2 diabetes; little is known about its possible association with cancer. To check
      this association we determined the distribution of its genotypes and frequency of
      alleles in endometrial cancer patients with or without overweight/obesity as
      compared to appropriate controls. The Trp64Arg polymorphism was determined by PCR
      based MspI restriction fragment length polymorphism in DNA of peripheral blood
      leukocytes. The study population consisted of 169 subjects, among them were 79
      endometrial cancer patients and 90 controls without cancer. There were 34 obese
      (BMI > or = 30 kg/m2) and 22 overweight (30 BMI > or = BMI > or = 27 kg/m2)
      individuals among endometrial cancer patients. There was a significant (p <
      0.001) difference in genotype distribution and allele frequency between
      endometrial cancer patients and controls without cancer. The odds ratios for the
      Trp/Arg and Arg/Arg genotypes as well as for the Arg allele were considerably
      higher than 1. Analysis of the polymorphism in the cancer group patients due to
      BMI revealed that the distribution of genotypes and the frequency of alleles in
      obese/overweight patients differed significantly from those in patients with
      normal weight with an odds ratio for the Trp/Arg genotype and the Arg allele of
      about 4. The prevalence of the Arg allele of the Trp64Arg polymorphism in the
      beta3-adrenergic receptor gene may contribute to the susceptibility to
      endometrial cancer among obese/overweight individuals.

PMID- 15743037
TI  - Establishment of a subcutaneous model of the human extrahepatic bile duct
      carcinoma in nude mice via transplantation of histologically intact tumor tissue.
AB  - The purpose of the study was to establish the subcutaneous model of human
      extrahepatic bile duct carcinoma in nude mice so as to provide a suitable model
      for the study of extrahepatic bile duct carcinoma. Surgical specimens of the
      patient with extrahepatic bile duct carcinoma were transplanted into the
      subcutaneous layer of nude mice. Growth curve of transplanted tumors was drawn
      and its morphological and biological characteristics, as well as choromosome were
      observed. A well differentiated mucinous adenocarcinoma model of human bile duct
      carcinoma in nude mice, designated as HBDCM1-ZSH (Human Bile Duct Carcinoma Model
      No. 1 established by Zhong Shan Hospital in April, 2001), was established via
      subcutaneous transplantation of the surgically resected tumor from a 56-year-old
      Chinese man. HBDCM1-ZSH has been maintained for 13 passages and exhibited 98.1%
      transplantability. Mean latent periods were 26 days. Transplanted tumors
      exhibited the characteristics of the original tumor in morphology and biology.
      Chromosomal analysis revealed numerical abnormalities ranging from 67 to 84.
      HBDCM1-ZSH expressed carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19
      9, cytokeratin (CK7, CK19, CK20), PCNA, AB and PAS. In conclusion, HBDCM1-ZSH is
      similar to human extrahepatic bile duct carcinoma and provides an applicable
      animal model for research on extrahepatic bile duct carcinoma.

PMID- 15743039
TI  - Effects of X-ray irradiation on the overexpression of HER-2/Erb-B2 on breast
      cancer cell lines.
AB  - Irradiation is the conventional treatment modality for cancer patients. However,
      besides its cytotoxic effects on malignant cells it might also affect the biology
      of surviving cells. Since overexpression of HER-2 receptors on malignant cells is
      a prerequisite for the therapeutic efficacy of Herceptin, it seems important to
      know whether previous irradiation changes their overexpression. The experiments
      performed in this work were aimed to determine whether X-ray irradiation of MDA
      MB-361 and MDA-MB-453 breast carcinoma cell lines, besides its cytotoxic action,
      affects the overexpression of HER-2 protein. Determination of the cytotoxic
      effect of X-ray irradiation was done using trypan blue test. The breast carcinoma
      cell responsiveness to herceptin treatment in the presence of 10% fresh human
      serum (from healthy volunteer's) in the presence or absence of 25 microg/ml of
      herceptin, in vitro before and after cell-irradiation, was evaluated by MTT test.
      The degree of HER-2 overexpression was determined by immunocytochemistry, using
      DAKO HercepTest. Preliminary results obtained in this work showed that X-ray
      irradiation, besides its cytotoxic effect on malignant cells, could lead to
      overexpression of HER-2 receptors on (initially by immunocytochemistry, HER-2
      negative) tumor cells, indicating change in biology of treated tumor cells.
      Further investigation in this direction will probably be helpful to elucidate
      this task in order to improve the selection of irradiated patients for Herceptin
      therapy.

PMID- 15743040
TI  - Modulation of tumor induced angiogenesis in Ehrlich ascites tumor.
AB  - In this study the enzyme glutaminase, purified from the ascites fluid of ovarian
      cancer patients, was analysed for its antiangiogenic activity. Intraperitoneal
      administration of this enzyme reduces the number of tumor directed capillaries in
      solid and ascites tumor bearing Swiss mice induced by transplantation of Ehrlich
      ascites cells. The enzyme has a critical role in regulating the secretion of
      vascular endothelial growth factor (VEGF) from tumor cell and in turn tumor
      growth. Glutamine analogue like 6-diazo, 5- oxo L-norleucine (DON) is also found
      to be effective in regulating vascular endothelial growth factor (VEGF) secretion
      from tumor cells in vitro. Treatment with enzyme reduced serum VEGF levels of the
      tumor induced animals. In vitro VEGF production by EAC cells was reduced in a
      concentration dependent manner in presence of glutamine analogue.

PMID- 15743041
TI  - Primary small cell neuroendocrine carcinoma of the breast.
AB  - We report and characterize immunohistochemically a case of primary small cell
      neuroendocrine carcinoma of the breast. The tumor, which arose in the left side,
      was 18 cm in maximum diameter and microscopically was composed of patternless
      sheets of undifferentiated small cells with a high nuclear-to-cytoplasmic ratio,
      hyperchromatic nuclei with indistinct cytoplasm, inconspicuous nucleoli, numerous
      mitotic figures and large areas of coagulative necrosis. Tumor cells were
      positive for bcl-2, neuron-specific enolase, synaptophysin, CAM 5.2 and
      cytokeratin AE1/3, but negative for LCA, CD30, HMB-45, chromogranin A, estrogen
      receptor, progesterone receptor, Her-2/neu and CD99. The opposite breast
      harboured an intraductal carcinoma with a focus suggesting microinfiltration, a
      finding never reported before. In this paper we have also extensively reviewed
      the literature on the subject, emphasizing the variable immunohistochemical
      profile and the aggressiveness of mammary small cell carcinoma. The rapidly fatal
      clinical course of our case, which appears to have the largest dimensions
      described in literature, underlines the importance of an early diagnosis and
      treatment for long-term survival.

PMID- 15743042
TI  - The role of alpha-interferon in chronic myelogenous leukaemia in Imatinib era.

PMID- 15743043
TI  - Alberta RN editorial content.

PMID- 15743044
TI  - Three generations of nurses and 100 years of service.

PMID- 15743045
TI  - Using high-tech to enhance RN touch.

PMID- 15743046
TI  - RNs: Taking a stand on tobacco reduction.

PMID- 15743047
TI  - Celebrating life in the midst of tragedy. Memoirs of a Congolese refugee camp.

PMID- 15743048
TI  - Primary osteosarcoma of the breast.
AB  - Primary osteosarcoma of the breast is a rare malignant tumor. We report on an 80
      year-old woman who presented with a right breast lump and a mammogram suggestive
      of carcinoma. The lesion was excised and histological features of the tumor were
      consistent with primary osteosarcoma. Due to insufficient resection margins,
      segmental mastectomy was performed to establish clear margins and failed to show
      any remaining tumor. There was no evidence of a separate primary tumor, and a
      metastatic work-up was unrevealing. We determined that primary treatment with
      segmental mastectomy was adequate and no further treatment was necessary. She
      remains disease free at 15 months.

PMID- 15743049
TI  - Educating health care providers.

PMID- 15743050
TI  - Delaware health plans encourage retinal eye exams for patients with diabetes.

PMID- 15743058
TI  - Nutrition management tools and techniques for working with students with
      diabetes.

PMID- 15743060
TI  - Continued emphasis on certification.

PMID- 15743059
TI  - Label reading 101. Can reading labels help children make healthier food choices?

PMID- 15743061
TI  - Exploring the role of the school nurse in promoting student achievement.

PMID- 15743062
TI  - The face of diversity. Challenges in school health.

PMID- 15743063
TI  - Identifying ways school nurses can support grieving children and adolescents.
AB  - This article is from the new 30-hour course book for nurses, Death, dying and
      bereavement: Providing compassion in a time of need, by Barbara Rubel BS, MA,
      CBS, BCETS, sold through www.westernschools.com. Western Schools is accredited as
      a provider of continuing education in Nursing by the American Nurses'
      Credentialing Center's Commission on Accreditation (ANCC).

PMID- 15743064
TI  - Convergent electron beam induced growth of copper nanostructures: evidence of the
      importance of a soft template.

PMID- 15743065
TI  - Interactions between two polyelectrolyte multilayers investigated by the surface
      force apparatus.

PMID- 15743067
TI  - Finger instability in Wetting-Dewetting phenomena.

PMID- 15743066
TI  - Nanostructured metal surfaces fabricated by a nonlithographic template method.

PMID- 15743068
TI  - One pot, spontaneous and simultaneous synthesis of gold nanoparticles in aqueous
      and nonpolar organic solvents using a diamine-containing oxyethylene linkage.

PMID- 15743069
TI  - Detection of organic mercaptan vapors using thin films of alkylamine-passivated
      gold nanocrystals.

PMID- 15743071
TI  - Surface ordering of amphiphilic ionic liquids.

PMID- 15743070
TI  - Solvent and temperature effects on the chiral aggregation of optically active
      poly(dialkylsilane)s confined in microcapsules.

PMID- 15743072
TI  - Temperature-responsive formation of colloidal nanoparticles from poly(N
      isopropylacrylamide) grafted with single-stranded DNA.
AB  - The thermal properties and temperature-responsive nanoparticle formation of
      poly(N-isopropylacrylamide) grafted with single-stranded DNA (PNIPAAm-g-DNA) were
      investigated. Copolymerization between nonamer single-stranded DNA with a vinyl
      group at its 5' terminus (DNA macromonomer) and NIPAAm was carried out so that
      the DNA macromonomer unit content should be less than 1 mol %. The turbidimetry
      and differential scanning calorimetry of the copolymer showed that the transition
      temperature increased and the enthalpy change of the phase transition decreased
      with increasing DNA macromonomer content in the copolymers, indicating that the
      DNA macromonomer behaves as a hydrophilic part in the copolymer and that the
      hydrophilicity is greater than that of sodium styrenesulfonate. Above the phase
      transition temperature, the copolymers formed colloidal nanoparticles with a
      dehydrated PNIPAAm core surrounded by DNA. When the formation of particles was
      conducted at higher temperatures, the dehydration of the copolymers proceeded
      such that the hydrodynamic radius (Rh) of the particles decreased. From the
      results of light scattering measurements, we calculated the surface area of
      particles occupied by one DNA (S(DNA)). The S(DNA) value decreased with
      increasing formation temperature, indicating that the DNA density on the particle
      surface increases with increasing formation temperature. The increase in the DNA
      density was also confirmed from the zeta-potential measurement of the particle.
      When MgCl2 was added to the copolymer solutions, the anionic charge of DNA was
      neutralized by Mg2+ so that Rh and the molecular weight of the particles
      increased with the increasing MgCl2 concentration. The turbidimetric detection of
      a target DNA was successfully demonstrated by utilizing the stability decrease of
      the colloidal particle upon hybridization on the particle surface.

PMID- 15743073
TI  - Thermodynamics of demicellization of mixed micelles composed of sodium oleate and
      bile salts.
AB  - Isothermal titration calorimetry (ITC) was used to determine the critical micelle
      concentration (cmc) and the thermodynamic parameters associated with the
      demicellization of sodium oleate (NaO) and mixed micelles composed of the bile
      salt (BS) sodium cholate (NaC) or sodium deoxycholate (NaDC), respectively, and
      NaO at a molar ratio of 5:2. The influence of the ionic strength (pure water and
      0.1 M NaCl at pH 7.5) as well as that of the temperature (10-70 degrees C) were
      analyzed. For NaO, two cmc's were detected, indicating a two-step aggregation
      process, whereas only one cmc was observed for the two BSs. A single aggregation
      mechanism is also evident for the demicellization of mixed micelles (BS/NaO 5:2).
      Increasing the ionic strength induces the well-known decrease of the cmc. The cmc
      shows a minimum at room temperature. The cmc(mix) of the mixed micelles was
      analyzed using models assuming an ideal or nonideal mixing behavior of both
      detergents. The thermodynamic parameters describing the enthalpy (deltaHdemic),
      entropy (deltaSdemic), and Gibbs energy change (deltaGdemic), as well as the
      change in heat capacity (deltaCp,demic) for demicellization, were obtained from
      one ITC experiment. From the temperature dependence of deltaHdemic, the change of
      the hydrophobic surface area of the detergents from the micellar into the aqueous
      phase was derived. In all cases, the deltaCp,demic values are positive. In
      addition, the temperature dependence of the size of the formed aggregates was
      studied by dynamic light scattering (DLS). DLS indicated two populations of
      aggregates in the mixed system, small primary micelles (0.5-2 nm), and larger
      aggregates with a hydrodynamic radius in the range of 50-150 nm.

PMID- 15743074
TI  - Solvation dynamics of formamide and N,N-dimethylformamide in aerosol OT reverse
      micelles.
AB  - The solvation dynamics of formamide and N,N-dimethylformamide in Aerosol OT
      reverse micelles has been investigated in this work. The solvation dynamics of
      formamide and N,N-dimethylformamide in the reverse micelles is more than 100
      times slower than that of the pure solvents. The solvation dynamics of formamide
      in the reverse micelle solution depends strongly on the molar ratio between
      formamide and Aerosol OT (w = [polar solvent]/[Aerosol OT]), but that of N,N
      dimethylformamide in the reverse micelle solution shows a tiny w dependence. We
      have estimated the interaction energies of the geometry-optimized clusters of a
      simple model of the Aerosol OT polar headgroup (CH3SO3-) and formamide or N,N
      dimethylformamide by ab initio calculations (the second-order Moller-Plesset
      perturbation theory) to find their interactions. The interaction energies of the
      mimic clusters estimated by the ab initio calculations and the features of the
      slow solvation dynamics and w dependence in formamide and N,N-dimethylformamide
      reverse micelles are discussed.

PMID- 15743075
TI  - Aqueous microemulsions of a fluorinated surfactant and oil studied by PFG-NMR:
      transformation from threadlike to spherical micelles.
AB  - The aqueous microemulsion system consisting of the fluorinated surfactant
      tetraethylammonium perfluorooctylsulfonate (TEAFOS) and the fluorinated oil 1H
      perfluorohexane (PFH) has been investigated using the pulsed field gradient NMR
      self-diffusion method on both 1H and 19F. Neat TEAFOS(aq) builds threadlike
      micelles from rather low surfactant concentrations up to ca. 80 mmol kg(-1). The
      addition of PFH to TEAFOS(aq) solutions induces a transition from threadlike
      micelles to spherical micelles solubilizing the oil. In this paper, information
      from the self-diffusion coefficients of oil (PFH), surfactant counterion (TEA+),
      surfactant ion (FOS-), and water (HDO) during the transition is presented.

PMID- 15743076
TI  - Study of the chromonic liquid-crystalline phases of bis-(N,N
      diethylaminoethyl)perylene-3,4,9,10-tetracarboxylic diimide dihydrochloride by
      polarized optical microscopy and 2H NMR spectroscopy.
AB  - The chromonic liquid-crystalline properties of bis-(N,N
      diethylaminoethyl)perylene-3,4,9,10-tetracarboxylic diimide dihydrochloride in an
      aqueous solution were investigated by polarized light microscopy and 2H NMR
      spectroscopy. Both techniques indicate a narrow I + N biphasic region and a broad
      N phase region at concentrations ranging from approximately 6.9 to approximately
      30 wt % at room temperature. Optical microscopy indicates that a hexagonal M
      phase exists at higher concentrations. The variation of the I --> N + I and N + I
      --> N transition temperatures with concentration was studied by 2H NMR
      spectroscopy. Finally, the effects of temperature and concentration on the order
      parameter of the N phase were investigated by 2H NMR using a tetra-deuterated
      derivative. A value of 0.97 was obtained for the N phase at its upper
      concentration limit.

PMID- 15743077
TI  - Evaluation of the stability of nonfouling ultrathin poly(ethylene glycol) films
      for silicon-based microdevices.
AB  - The creation of nonfouling surfaces is one of the major prerequisites for
      microdevices for biomedical and analytical applications. Poly(ethylene glycol)
      (PEG), a water soluble, nontoxic, and nonimmunogenic polymer has the unique
      ability of reducing nonspecific protein adsorption and cell adhesion and,
      therefore, is generally coupled with a wide variety of surfaces to improve their
      biocompatibility. The performance of these modified surfaces for long-term
      biomedical applications largely depends on the stability of these PEG films. To
      this end, we have investigated the stability of covalently coupled ultrathin PEG
      films on silicon in aqueous in vivo like conditions for a period of 4 weeks. The
      PEG-modified silicon substrates were incubated in PBS (37 degrees C, pH 7.4, 5%
      CO2) for different periods of time and then characterized using the techniques of
      ellipsometry, contact angle measurement, X-ray photoelectron spectroscopy, and
      atomic force microscopy. The ability of the PEG-modified surfaces to control
      protein fouling was examined by protein adsorption studies using fluorescein
      isothiocyanate labeled bovine serum albumin and ellipsometry. Furthermore, the
      ability of these films to control fibroblast adhesion was examined. Studies
      suggest that the PEG-modified surfaces retain their protein and cell repulsive
      nature even though the PEG film thickness decreases for the period of
      investigation.

PMID- 15743078
TI  - Cd2+-induced interfacial structural changes of Langmuir-Blodgett films of stearic
      acid on solid substrates: a sum frequency generation study.
AB  - The molecular structures and their stabilities at the outmost-layer of the
      Langmuir-Blodgett (LB) films of stearic acid on solid substrates have been
      investigated by a highly surface-sensitive spectroscopic technique, sum frequency
      generation (SFG), in air and in aqueous solution, using the combination of both
      normal and deuterated stearic acid. Peaks observed in the SFG spectra are mainly
      attributed to the terminal methyl group at the outmost layer of the LB films. The
      SFG spectra in air are virtually identical and are independent of the odd-even
      property and thickness (1-12) of the LB films, indicating that the even-numbered
      LB film changes its surface structure after passing through the interface between
      the water subphase and air, especially when the Cd2+ cation was included in the
      water subphase. Furthermore, we have demonstrated for the first time using in
      situ SFG measurement that the interfacial molecular structure at the LB bilayer
      of stearic acid on the hydrophilic substrates significantly change with immersion
      in the water subphase containing Cd2+ cation while such a structural change has
      not been observed in the water subphase without Cd2+. These results clearly
      indicate that a reorganization process takes place on the surface of the stearic
      acid bilayer induced by the Cd2+ cation. The electrostatic interaction between
      the carboxylate headgroup of stearic acid via the Cd2+ cation seems to play an
      important role in the surface reorganization process both in air and in solution.

PMID- 15743079
TI  - Si-C(N) sigma linkages and N --> Si dative bonding at pyridine/Si(111)-7 x 7.
AB  - We experimentally demonstrated that pyridine/Si(111)-7 x 7 can act as an electron
      donor/acceptor pair as a result of the charge transfer from the electron-rich N
      atom of pyridine to the electron-deficient adatom of the Si surface, evidenced by
      the upshift of 1.8 eV (state A) for the N(1s) core level upon the formation of a
      datively bonded complex compared to physisorbed molecules. Another state (B)
      whose N(1s) binding energy downshifts by 1.2 eV was assigned to an adduct through
      Si-C and Si-N covalent linkages, formed via a [4 + 2]-like addition mechanism on
      Si(111)-7 x 7. Binding molecules through the formation of the dative bond
      resulted from significant electron transfer opens a new approach for the creation
      of Si-based molecular architectures and modification of semiconductor interfacial
      properties with unsaturated organic molecules.

PMID- 15743080
TI  - Zeta-potential measurements as a tool to quantify the effect of charged drugs on
      the surface potential of egg phosphatidylcholine liposomes.
AB  - The binding of charged drugs to neutral phosphatidylcholine membranes was
      assessed by measuring their zeta-potential values in the presence of different
      drug concentrations. This methodology was applied to the study of the
      concentration effects of two nonsteroidal antiinflammatory drugs (NSAIDs).
      Results revealed an intense membrane charging that was proportional to the amount
      of negatively charged drug in the media. A mathematical formalism was adapted and
      an analytical expression derived to calculate directly surface potentials from
      zeta-potential data. The membrane loading state, expressed as the number of
      molecules per unit area, was calculated for the negative and for the neutral
      forms of the drugs. An approach was also developed that allows the determination
      of the maximum number of molecules per unit area by fitting a binding isotherm to
      the dependence of the number molecules per unit area with the drug concentration.
      The calculation of the maximum mol lipid/drug ratio can also be estimated and
      related to the binding stoichiometry, as well as to the maximum lipid loading
      capacity. Furthermore, the concentration profiles for both drugs can be
      established in terms of the distance to the liposome surface. The developed
      methodology allowed for the simultaneous determination of partition coefficients
      (Kp) for the NSAIDs in lipid/aqueous media because zeta-potential values can be
      related to the drug concentration at the lipid/ aqueous media interface.
      Alternative independent methodologies were used to determine Kp:
      spectrophotometric and centrifugation assays. A mathematical relation was
      developed to compare the Kp values determined from the zeta-potential data with
      those obtained from the other techniques used because in the former case they are
      calculated on the basis of the number of molecules per unit area and in the
      latter on the basis of the total drug concentrations in solution, and the values
      of the partition coefficients obtained from all the techniques were found to be
      equal, within the experimental error. This methodology constitutes a more
      straightforward method than the other techniques used because partition
      coefficients for all drug forms (charged and noncharged) can be assessed with a
      minimum number of experimental determinations and it allows for a
      characterization of the electrostatic properties of neutral membranes upon
      binding of charged drugs.

PMID- 15743081
TI  - Proximal adsorption at glass surfaces: ionic strength, pH, chain length effects.
AB  - The adsorption and desorption of pyridinium chloride surfactants on borosilicate
      glass are studied as a function of the separation between two glass-solution
      interfaces. Both the adsorption and desorption change exponentially with the
      separation; the decay is equal to the solution Debye length. Changes in
      adsorption are smaller at pH 1.8 (near the point of zero charge of glass) than at
      pH 6. These results are consistent with an electrostatic cause for the changes in
      adsorption. The magnitude of the adsorption regulation, however, depends on the
      length of the alkyl chain and the surface excess of the surfactant. Therefore,
      proximal adsorption in this system depends on the coupling between the long-range
      electrostatic forces and the short-range chain-chain interactions. The equation
      of state for the surfactant on a regulating surface is discussed with respect to
      changes in intersurface separation.

PMID- 15743082
TI  - Study of hexane adsorption in nanoporous MCM-41 silica.
AB  - We study here the adsorption of hexane on nanoporous MCM-41 silica at 303,313,
      and 323 K, for various pore diameters between 2.40 and 4.24 nm. Adsorption
      equilibria, measured thermogravimetrically, show that all the isotherms, that are
      somewhat akin to those of type V, exhibit remarkably sharp capillary adsorption
      phase transition steps and are reversible. The position of the phase transition
      step gradually shifts from low to high relative pressure with an increase in the
      temperature as well as the pore sizes. The isosteric heats of adsorption derived
      from the equilibrium information using the Clapeyron equation reveal a gradual
      decrease with increasing adsorbed amount because of the surface heterogeneity but
      approach a constant value near the phase transition. A decrease in the pore size
      results in an increase in the isosteric heat of adsorption because of the
      increased dispersion forces. A simple strategy, based on the Broekhoff and De
      Boer adsorption theory, successfully interprets the hexane adsorption isotherms
      for the different pore size MCM-41 samples. The parameters of an empirical
      expression, used to represent the potential of interaction between the adsorbate
      and adsorbent, are obtained by fitting the monolayer region prior to capillary
      condensation and the experimental phase transition simultaneously, for some pore
      sizes. Subsequently, the parameters are used to predict the adsorption isotherm
      on other pore size samples, which showed good agreement with experimental data.

PMID- 15743083
TI  - Hydrogel characteristics of electron-beam-immobilized poly(vinylpyrrolidone)
      films on poly(ethylene terephthalate) supports.
AB  - A novel strategy for the preparation of thin hydrogel coatings on top of polymer
      bulk materials was elaborated for the example of poly(ethylene terephthalate)
      (PET) surfaces layered with poly(vinylpyrrolidone) (PVP). PVP layers were
      deposited on PET foils or SiO2 surfaces (silicon wafer or glass coverslips)
      precoated with PET and subsequently cross-linked by electron beam treatment. The
      obtained films were characterized by ellipsometry, X-ray photoelectron
      spectroscopy, infrared spectroscopy in attenuated total reflection, atomic force
      microscopy (AFM), and electrokinetic measurements. Ellipsometric experiments and
      AFM force-distance measurements showed that the cross-linked layers swell in
      aqueous solutions by a factor of about 7. Electrokinetic experiments indicated a
      strong hydrodynamic shielding of the charge of the underlying PET layer by the
      hydrogel coatings and further proved that the swollen films were stable against
      shear stress and variation of pH. In conclusion, electron beam cross-linking
      ofpreadsorbed hydrophilic polymers permits a durable fixation of swellable
      polymer networks on polymer supports which can be adapted to materials in a wide
      variety of shapes.

PMID- 15743084
TI  - Pseudopartial wetting and precursor film growth in immiscible metal systems.
AB  - We explore the equilibrium wetting behavior and precursor film growth in pure and
      alloy metallic systems. The systems exhibit equilibrium "pseudopartial" wetting,
      that is, a thin film in equilibrium with a nonzero contact angle in both liquid
      and solid states. The film spreading kinetics clearly indicates a diffusive
      transport mechanism. The alloying has only a small impact on the equilibrium
      wetting properties but strongly affects the transport during the growth of the
      precursor film.

PMID- 15743085
TI  - Phase behavior and phase-transfer catalysis of tetrabutylammonium salts.
      Interface-mediated catalysis.
AB  - The phase behavior and component composition of the coexisting phases in the
      tetrabutylammonium bromide (TBABr)/benzene/water/NaBr four-component system were
      strongly influenced by the temperature, TBABr content, and NaBr concentration.
      The phase-transfer catalytic activity of TBABr for the reaction of decyl
      methanesulfonate with sodium bromide was closely related to the phase behavior.
      Under O (oil-rich phase) + L (TBABr-rich liquid phase) + W (aqueous phase)
      triphase conditions, the influences of temperature and stirring speed on the
      phase-transfer catalytic activity were small compared with those under O + W
      biphase conditions. The addition of other quaternary salts that were able to form
      w/o aggregates in the O phase enhanced the TBABr catalytic activity even under O
      + W conditions. The relationship between phase behavior and catalytic activity of
      tetrabutylammonium chloride or iodide (TBACl or TBAI) was also examined. The
      results strongly suggested that the catalysis of TBAX was attributable to the
      interfacial reactions of TBAX with the substrate. The interface includes the
      water-oil microinterface formed in the microemulsion-like L phase as well as the
      bulk water-oil interface.

PMID- 15743086
TI  - Characterization of nanoporous low-k thin films by small-angle neutron scattering
      contrast variation.
AB  - Small-angle neutron scattering contrast variation is applied to characterization
      of nanoporous low-dielectric constant (low-k) thin films. Films are exposed to
      saturated solvent vapor in air, whereby the pores fill with liquid by capillary
      condensation. The pores are filled with mixtures of hydrogen- and deuterium
      containing solvents to vary the neutron contrast with the matrix (wall). The
      composition of the solvent mixture is systematically varied to identify a
      composition that minimizes the scattered intensity (contrast match point). From
      the contrast match point composition, film characteristics including matrix
      density and homogeneity are assessed. Four spin-on low-k materials including a
      methylsilsesquioxane, an organic polymer, a xerogel, and a hydrogensilsesquioxane
      are characterized by the new technique. Calculated matrix mass densities are
      compared to independent density measurements obtained by an established specular
      X-ray reflectivity technique. We find no evidence of "closed pores", defined here
      as pores inaccessible to the probe solvent, in any of the materials studied.

PMID- 15743087
TI  - Reduction of friction at oxide interfaces upon polymer adsorption from aqueous
      solutions.
AB  - Reduction of the interfacial friction for the contact of a silicon oxide surface
      with sodium borosilicate in aqueous solutions has been accomplished through the
      adsorption of poly(L-lysine)-graft-poly(ethylene glycol) on one or both surfaces.
      Spontaneous polymer adsorption has been achieved via the electrostatic attraction
      of the cationic polylysine polymer backbone and a net negative surface charge,
      present for a specific range of solution pH values. Interfacial friction has been
      measured in aqueous solution, in the absence of wear, and on a microscopic scale
      with atomic force microscopy. The successful investigation of the polymer-coated
      interfaces has been aided by the use of sodium borosilicate microspheres (5.1
      microm diameter) as the contacting probe tip. Measurements of interfacial
      friction as a function of applied load reveal a significant reduction in friction
      upon the adsorption of the polymer, as well as sensitivity to the coated nature
      of the interface (single-sided versus two-sided) and the composition of the
      adsorbed polymer. These measurements demonstrate the fundamental opportunity for
      lubrication in aqueous environments through the selective adsorption of polymer
      coatings.

PMID- 15743088
TI  - Quantitative characterization of DNA films by X-ray photoelectron spectroscopy.
AB  - We describe the use of self-assembled films of thiolated (dT)25 single-stranded
      DNA (ssDNA) on gold as a model system for quantitative characterization of DNA
      films by X-ray photoelectron spectroscopy (XPS). We evaluate the applicability of
      a uniform and homogeneous overlayer-substrate model for data analysis, examine
      model parameters used to describe DNA films (e.g., density and electron
      attenuation length), and validate the results. The model is used to obtain
      quantitative composition and coverage information as a function of immobilization
      time. We find that when the electron attenuation effects are properly included in
      the XPS data analysis, excellent agreement is obtained with Fourier transform
      infrared (FTIR) measurements for relative values of the DNA coverage, and the
      calculated absolute coverage is consistent with a previous radiolabeling study.
      Based on the effectiveness of the analysis procedure for model (dT)25 ssDNA
      films, it should be generally valid for direct quantitative comparison of DNA
      films prepared under widely varying conditions.

PMID- 15743089
TI  - Binding the tobacco mosaic virus to inorganic surfaces.
AB  - We studied the adsorption behavior and surface chemistry of the tobacco mosaic
      virus (TMV) on well-defined metal and insulator surfaces. TMV serves as a tubular
      supramolecular model system with precisely known surface termination. We show
      that if the surface chemistry of the substrate and the pH-dependent chemistry of
      the molecular surface match, for example, by hydrogen bonding, a strong
      adsorption occurs, and lateral movement is impeded. Due to the immobilization,
      the virion can be imaged by atomic force microscopy (AFM) in contact mode. We
      also used self-assembled monolayers with an acyl chloride group to induce
      covalent bonding via ester formation. Noncontact AFM proved that TMV keeps its
      cylindrical cross section only under weak adsorption conditions, that is, on
      hydrophobic surfaces, while on hydrophilic substrates a deformation occurs to
      maximize the number of interacting chemical groups.

PMID- 15743090
TI  - Layer by layer buildup of polysaccharide films: physical chemistry and cellular
      adhesion aspects.
AB  - The formation ofpolysaccharide films based on the alternate deposition of
      chitosan (CHI) and hyaluronan (HA) was investigated by several techniques. The
      multilayer buildup takes place in two stages: during the first stage, the surface
      is covered by isolated islets that grow and coalesce as the construction goes on.
      After several deposition steps, a continuous film is formed and the second stage
      of the buildup process takes place. The whole process is characterized by an
      exponential increase of the mass and thickness of the film with the number of
      deposition steps. This exponential growth mechanism is related to the ability of
      the polycation to diffuse "in" and "out" of the whole film at each deposition
      step. Using confocal laser microscopy and fluorescently labeled CHI, we show that
      such a diffusion behavior, already observed with poly(L-lysine) as a polycation,
      is also found with CHI, a polycation presenting a large persistence length. We
      also analyze the effect of the molecular weight (MW) of the diffusing
      polyelectrolyte (CHI) on the buildup process and observe a faster growth for low
      MW chitosan. The influence of the salt concentration during buildup is also
      investigated. Whereas the CHI/HA films grow rapidly at high salt concentration
      (0.15 M NaCl) with the formation of a uniform film after only a few deposition
      steps, it is very difficult to build the film at 10(-4) M NaCl. In this latter
      case, the deposited mass increases linearly with the number of deposition steps
      and the first deposition stage, where the surface is covered by islets, lasts at
      least up to 50 bilayer deposition steps. However, even at these low salt
      concentrations and in the islet configuration, CHI chains seem to diffuse in and
      out of the CHI/HA complexes. The linear mass increase of the film with the number
      of deposition steps despite the CHI diffusion is explained by a partial
      redissolution of the CHI/HA complexes forming the film during different steps of
      the buildup process. Finally, the uniform films built at high salt concentrations
      were also found to be chondrocyte resistant and, more interestingly, bacterial
      resistant. Therefore, the (CHI/HA) films may be used as an antimicrobial coating.

PMID- 15743091
TI  - Effects of organic additives on zinc electrodeposition at iron electrodes studied
      by EQCM and in situ STM.
AB  - Effects of organic additives, such as benzoic acid (BA) and poly(ethylene
      glycol)s (PEGs), on the initial stage of the zinc electrodeposition have been
      investigated at iron electrodes using cyclic voltammetry, electrochemical quartz
      crystal microbalance measurements and in situ electrochemical scanning tunneling
      microscopy in an acidic zinc chloride solution in efforts to gain a molecular
      level understanding of their roles. BA is adsorbed strongly at the sites of more
      negative potentials on the electrode, although it is randomly adsorbed on the
      iron surface at around an open circuit potential. Its role seems to control the
      deposition rate at the dendritic sites by blocking the active surface via
      adsorption. On the contrary, PEGs are adsorbed more or less evenly with a well
      ordered structure on the iron surface and appear to desorb in the underpotential
      deposition region of zinc ions, which helps inhibit proton reduction by
      effectively blocking the electrode surface.

PMID- 15743092
TI  - Control and modeling of the dielectrophoretic assembly of on-chip nanoparticle
      wires.
AB  - Suspensions of metallic nanoparticles in water were assembled via the action of
      an alternating electric field (dielectrophoresis) into wires of micrometer
      thickness. Two modes of microwire assembly, one through the bulk of the
      suspension and one as half-cylinders on the glass surface between the electrodes,
      were identified. The operating conditions responsible for the two assembly modes
      were recognized. The control of the process parameters allows making, for
      example, straight single connectors or massively parallel arrays of microwires on
      the surface of the chip, which can be extracted in dry form. The microwire
      assembly process was modeled using finite element electrostatic calculations. The
      direction of growth can be guided by introducing conductive islands or particles
      in the suspension. The experiments, supported by electrostatic calculations, show
      that the wires grow in the direction of highest field intensity, "automatically"
      making electrical connections to the objects between the electrodes. The results
      point the way to controlled dielectrophoretic assembly of nanoparticles into on
      chip electrical connectors, switches, and networks.

PMID- 15743093
TI  - Self-assembly of a hexagonal phase of wormlike micelles containing metal
      nanoclusters.
AB  - Stable nanoclusters (approximately 2 nm in diameter) of copper, silver, gold,
      palladium, and ruthenium coated with hydrophobic coronas are easily trapped in
      self-assembled "soft crystal" hexagonal phase gels made of water and surfactants.
      The system's crystal structure and phase behavior are studied in detail. A
      partial phase diagram showing the hexagonal phase region for the
      water/SDS/toluene region is presented. High-energy X-ray scattering and cross
      polarized optical microscopy experiments show that the clusters are tightly
      confined within the tubes. The thermal gel-fluid transitions of the hexagonal
      phase are investigated, and it is shown that the hexagonal phase can melt and
      recrystallize repeatedly. The melt/gel cycles enable easy trapping of various
      metal clusters in pre-prepared hexagonal phases. In contrast to spherical
      micelles, the hexagonal phase doped with metal clusters can grow without limit,
      basically up to the container walls (Ru-doped soft crystals grew to 0.5 mm over 2
      months, forming wormlike tubes that are more than 50 microm long but only 7-10 nm
      in diameter).

PMID- 15743094
TI  - Supramolecular self-assembly of inclusion complexes of a multiarm hyperbranched
      polyether with cyclodextrins.
AB  - A new class of crystalline inclusion complexes of a multiarm hyperbranched
      polyether combined with various cyclodextrins (CDs) was successfully prepared.
      Using self-condensing ring-opening polymerization, a kind of multiarm polyether
      with a hyperbranched poly(3-ethyl-3-oxetanemethanol) core and multiple linear
      poly(ethylene glycol) (PEG) arms was obtained. It has been found that this kind
      of hyperbranched polyether can be dissolved in water. Adding alpha-CDs to the
      multiarm hyperbranched polyether solution, molecular recognition results in the
      formation of crystalline inclusion complexes based on the noncovalent
      interactions between the linear PEG arms of the polyether particles and the alpha
      CDs. These multiarm polyether inclusion complexes have been well characterized.
      Interestingly, quite different from inclusion complexes of CDs and linear
      polymeric guests, the complexes of the multiarm hyperbranched polyether with
      alpha-CDs show a novel lamellar morphology. The experimental results validate
      that the resultant lamellar crystals have a juxtaposed structure. In addition,
      the formation mechanism of these inclusion complexes of a multiarm polyether with
      alpha-CDs has also been well described. Besides the role of displacement of
      associated water molecules and the presence of hydrogen bonding between CDs in
      channel structure CD inclusion complexes, the noncovalent intermolecular forces
      between CDs and polymers also play an important role in the formation of complex
      architectures.

PMID- 15743095
TI  - Nonionic fluorinated surfactant: investigation of phase diagram and preparation
      of ordered mesoporous materials.
AB  - The behavior of fluorinated surfactant F(CF2)8C2H4(OC2H4)9OH in water solution
      was investigated, and the preparation ofmesoporous molecular sieves was achieved.
      A direct micellar phase (L1) and a hexagonal (H1) liquid crystal were found.
      Small-angle X-ray scattering measurements proved that the hydrophobic chains are
      completely extended and that the cross sectional area remains constant in H1. At
      80 degrees C, materials with a hexagonal array of their channel are prepared via
      a cooperative templating type mechanism in a wide range of surfactant
      concentrations (5-20 wt %). Decreasing the hydrothermal temperature leads to the
      formation ofwormhole-like structure. In this case the channel arrangement is no
      longer governed by the surfactant behavior but by the silica condensation and
      polymerization. An increase of the mean pore diameter with heating temperature is
      noted. This result is associated with changes of aggregation number with
      temperature. A comparison of the characteristics of the materials obtained with
      both hydrogenated and fluorinated surfactants is also made.

PMID- 15743096
TI  - Adsorption of a multicomponent mixture of gases with multisite occupancy.
AB  - In this paper, we present a study of the adsorption of multicomponent mixtures
      with multisite occupancy. The transfer-matrix technique is used to analyze the
      one-dimensional binary mixtures for interacting systems. A general expression for
      the characteristic polynomial is derived. Extension of the treatment to a higher
      dimension is also presented by using the mean-field Bragg-Williams approximation,
      transfer-matrix calculations, and Monte Carlo simulation. Partial and total
      isotherms are obtained for the dimer-trimer mixture where a different order
      appears.

PMID- 15743097
TI  - Dynamics of self-assembled chaining in magnetorheological fluids.
AB  - The aggregation dynamics of paramagnetic spherical particles embedded in a
      viscous fluid is investigated via numerical simulations using a fully coupled
      three-dimensional model. Particles experience simultaneously Brownian motion,
      dipolar magnetic attraction, and multibody hydrodynamic interactions. When the
      dipole strength characterizing the ratio of magnetic attraction to random
      diffusion exceeds a critical value, particles join together forming supraparticle
      structures. As time evolves, particle/chain and chain/ chain interactions lead to
      a continuous increase of the cluster size. The mean length of particle chains has
      a power-law dependence with respect to time, as predicted by the theory of
      diffusion-limited aggregation. Both the exponent and the characteristic time
      scale agree very well with the experimental results of Promislow et al.

PMID- 15743098
TI  - Lattice Monte Carlo simulations of phase separation and micellization in
      supercritical CO2/surfactant systems: effect of CO2 density.
AB  - Lattice Monte Carlo simulations are used to study the effect of nonionic
      surfactant concentration and CO2 density on the micellization and phase
      equilibria of supercritical CO2/surfactant systems. The interaction parameter for
      carbon dioxide is obtained by matching the critical temperature of the model
      fluid with the experimental critical temperature. Various properties such as the
      critical micelle concentration and the size, shape, and structure ofmicelles are
      calculated, and the phase diagram in the surfactant concentration-CO2 density
      space is constructed. On increasing the CO2 density, we find an increase in the
      critical micelle concentration and a decrease in the micellar size; this is
      consistent with existing experimental results. The variation of the micellar
      shape and structure with CO2 density shows that the micelles are spherical and
      that the extension of the micellar core increases with increasing micellar size,
      while the extension of the micellar corona increases with increasing CO2 density.
      The predicted phase diagram is in qualitative agreement with experimental phase
      diagrams for nonionic surfactants in carbon dioxide.

PMID- 15743099
TI  - Polyanion protection of silane bonds to silicon oxide revealed by electrokinetic
      measurements.

PMID- 15743100
TI  - Preparation of nanoparticles of poly(methyl methacrylate) Latexes at theta
      condition.

PMID- 15743101
TI  - Measurement of the adsorption of cytochrome c onto the external surface of a thin
      film mesoporous silicate by ellipsometry.

PMID- 15743102
TI  - A comparison of agents used to manage type 2 diabetes mellitus: need for
      reappraisal of traditional approaches.
AB  - In patients with type 2 diabetes mellitus, the traditional method of initiating
      therapy with a sulfonylurea and increasing the dosage until maximum levels are
      reached before adding an insulin-sensitizing agent has persisted and should be re
      evaluated. Similarly, the current practice of starting therapy with one agent and
      increasing to maximum dosage before adding a second agent, rather than starting
      with combination therapy, also needs to be addressed. There is much evidence to
      suggest that initiating therapy with lower doses of two agents that have
      complementary effects can increase the overall efficacy and decrease the
      incidence of adverse effects. Clearly, there is a need for a paradigm shift away
      from the traditional approach of therapy using insulin secretagogues to a more
      pathophysiologic approach using an insulin-sensitizing agent, such as the
      thiazolidinediones. The thiazolidinediones have been shown to reduce insulin
      resistance, improve the ability of beta-cells to produce insulin, and decrease
      cardiac risk factors. By reducing insulin resistance, improving glycemic control,
      and preserving beta-cell function with a thiazolidinedione early in the course of
      therapy, it is likely that durable glycemic control will be achieved and both
      microvascular and macrovascular complications may be reduced. Furthermore, early
      use of an insulin-sensitizing agent either alone or incombination is expected to
      improve both acute and long-term outcomes in patients with type 2 diabetes.

PMID- 15743103
TI  - Lanreotide Autogel for acromegaly: a new addition to the treatment armamentarium.
AB  - Since their introduction into clinical practice, somatostatin analogs have been
      the pharmacological therapy of choice for the treatment of acromegaly. The first
      preparations of somatostatin analogs available for clinical use were administered
      subcutaneously two or three times daily, which was not optimal with respect to
      patient compliance. The introduction of long-acting formulations of somatostatin
      analogs has overcome this inconvenience. Lanreotide Autogel, a new viscous,
      supersaturated, aqueous solution of lanreotide, is available in a prefilled
      syringe and administered by deep subcutaneous injection every 28 days. Lanreotide
      Autogel has different pharmacokinetic properties from the earlier lanreotide slow
      release (SR) formulation, which may account for its better tolerability.
      Furthermore, lanreotide Autogel is at least as efficacious as the other
      somatostatin analogs in lowering growth hormone (GH) and insulin-like growth
      factor-1 (IGF-1) levels in the majority and in restoring safe GH and age
      normalized IGF-1 levels in about 50-60% of patients with acromegaly. In
      conclusion, lanreotide Autogel is a valuable new addition to the acromegaly
      treatment armamentarium. Patients receiving intramuscular lanreotide SR
      injections every 7-14 days can be switched to an appropriate dose of deep
      subcutaneous lanreotide Autogel every 28 days, without any impact on safety or
      loss of efficacy.

PMID- 15743104
TI  - Optimizing gonadotropin-releasing hormone agonist therapy in women with
      endometriosis.
AB  - Endometriosis is a highly prevalent disease among women of reproductive age.
      While many treatments are available, one of the most widely utilized is treatment
      with gonadotropin-releasing hormone (GnRH) agonists. These agents work by
      producing a profound suppression of gonadotropin secretion by the pituitary,
      resulting in a hypoestrogenic state and subsequent diminution of endometriosis
      lesions. The GnRH agonists on the market have been shown to work quite well in
      reducing all pain symptoms associated with endometriosis, including dysmenorrhea,
      dyspareunia, and noncyclic pelvic pain. However, there is no evidence to suggest
      that this treatment is of value in endometriosis-associated infertility.
      Conflicting data exist regarding the role of GnRH agonists in the treatment of
      endometriomas, but the bulk of the evidence suggests a low degree of efficacy.
      GnRH agonists are often initiated with the onset of menses, but a more rapid
      response is observed with mid-luteal administration. A limit of 6 months per
      treatment course is required due to loss of bone mineral density during therapy,
      but this can be extended via the addition of 'add-back' therapy. Such adjunctive
      regimens demonstrated to maintain efficacy and reduce adverse effects include
      progestogen alone or a low-dose combination of estrogen and progestogen.
      Retreatment with these drugs is supported by limited data. The use of GnRH
      agonists as surgical adjuncts has been studied by several investigators. Their
      use preoperatively has not been shown to be of value. Similarly, 3 months of
      postoperative administration has failed to enhance treatment. However, 6 months
      of postoperative GnRH agonists appear to improve the duration of relief of pain
      symptoms. Future studies will need to focus on the role of these agents when used
      for repeated courses, in young women, and in conjunction with assisted
      reproduction.

PMID- 15743105
TI  - Hypoglycemia in type 1 diabetes mellitus: pathophysiology and prevention.
AB  - Spontaneous hypoglycemia is uncommon in the general (nondiabetic) population, but
      iatrogenic hypoglycemia is rife in patients with type 1 diabetes mellitus, among
      whom hypoglycemia constitutes a barrier to optimal glycemic control. The obligate
      dependence on exogenous insulin, together with the current imperfection in
      insulin therapies, generates degrees of blood glucose fluctuations that often
      exceed physiological boundaries in these patients. Downward swings in blood
      glucose levels, if sustained, result in hypoglycemia and significant morbidity
      and mortality. Hypoglycemia in type 1 diabetes indicates an imbalance between
      caloric supply and glucose use in response to insulin or exercise.
      Counterregulatory mechanisms that auto-correct iatrogenic hypoglycemia often
      become progressively impaired in these patients. This defective
      counterregulation, together with the imperfections in insulin delivery, set the
      stage for significant morbidity from iatrogenic hypoglycemia. Recurrent episodes
      of iatrogenic hypoglycemia induce a state of hypoglycemia unawareness and
      defective counterregulation, which defines the syndrome of hypoglycemia
      associated autonomic failure (HAAF). The reduced awareness of, and
      counterregulatory responses to, hypoglycemia in patients with HAAF lead to
      worsening episodes of severe hypoglycemia. Approaches to the prevention of
      hypoglycemia include glucose monitoring, patient education, meal planning, and
      medication adjustment. In patients with HAAF, scrupulous avoidance of iatrogenic
      hypoglycemia may restore the symptomatic and counterregulatory responses to
      hypoglycemia. Behavioral training focusing on recognition of the more subtle
      symptoms and signs of evolving hypoglycemia may be beneficial to some patients
      with HAAF. A methodical search for the pattern and etiology of iatrogenic
      hypoglycemia is a prerequisite for the identification of the best preventive
      approach. With proper education, patients with type 1 diabetes and their
      physicians can learn to prevent or minimize the risk of hypoglycemia while
      pursuing excellence in glycemic control.

PMID- 15743106
TI  - Hormone replacement therapy, selective estrogen receptor modulators, and tissue
      specific compounds: cardiovascular effects and clinical implications.
AB  - In industrialized countries, coronary heart disease (CHD) is not only the leading
      cause of death in women but of disability as well. Menopause, regardless of age
      at onset, is associated with a marked increase in CHD risk. Based on
      epidemiologic studies demonstrating mainly positive biologic effects of hormone
      replacement therapy (HRT) on CHD risk factors and outcomes, earlier
      recommendations decreed that most, if not all, postmenopausal women should be
      treated with long-term HRT. Recent randomized controlled trials with clinical CHD
      endpoints have shown that previously held dicta may not be accurate. Selective
      estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene are
      alternatives to HRT. SERMs represent a growing class of compounds that act as
      either estrogen receptor agonists or antagonists in a tissue-selective manner.
      This pharmacologic profile may offer the opportunity to dissociate favorable
      cardiovascular effects of estrogen from unfavorable stimulatory effects on the
      breast and endometrium. The only data available regarding the effects of
      tamoxifen on cardiovascular events in postmenopausal women are from breast cancer
      trials. They showed fewer fatal myocardial events in women randomly assigned to
      tamoxifen compared with women assigned to placebo. Raloxifene is a so-called
      second-generation SERM. It seems clear that raloxifene increases bone mineral
      density, has no effect on the endometrium, and holds high promise for the
      prevention of breast cancer. The effect of raloxifene on cardiovascular disease
      is uncertain. On the basis of the Multiple Outcomes of Raloxifene Evaluation
      (MORE) trial, raloxifene may offer some protection to women with cardiovascular
      disease or to those who are at high risk. Proof that raloxifene reduces the risk
      of CHD requires a clinical trial with hard clinical endpoints. Such a study is
      currently underway. Clinical trials have demonstrated that the synthetic 19
      nortestosterone derivative tibolone reduces climacteric complaints and prevent
      osteoporosis without causing menstrual bleeding. Tibolone lowers lipoprotein(a),
      fibrinogen, and plasminogen activator inhibitor-1 levels and improves glucose
      tolerance, insulin sensitivity, and endothelial function; however, it also lowers
      high-density lipoprotein cholesterol by >20%. The long-term impact of tibolone on
      the risk of CHD is not known and needs to be studied.

PMID- 15743107
TI  - Calcitonin therapy in osteoporosis.
AB  - Osteoporosis is the most prevalent metabolic bone disease and is characterized by
      diminished bone strength predisposing to an increased risk of fracture. Its
      incidence is particularly high in postmenopausal women but it can also affect
      other groups, such as men and patients receiving corticosteroid therapy.
      Calcitonin is a naturally occurring peptide which acts via specific receptors to
      strongly inhibit osteoclast function. It has been used in the treatment of
      osteoporosis for many years. Historically, calcitonin was administered as a
      parenteral injection, but the intranasal formulation is now the most widely used
      because of its improved tolerability. New approaches are currently being
      investigated to enhance the bioavailability and effects of calcitonin, including
      oral, pulmonary, and transdermal routes of administration, and novel allosteric
      activators of the calcitonin receptor. Several controlled trials have reported
      that calcitonin stabilizes and in some cases produces a short-term increase in
      bone density at the lumbar spine level. The most relevant clinical trial to
      evaluate the effect of calcitonin in the prevention of fractures was the Prevent
      Recurrence of Osteoporotic Fractures (PROOF) study, a 5-year double-blind,
      randomized, placebo-controlled trial showing that salmon calcitonin nasal spray
      at a dosage of 200 IU/day can reduce the risk of vertebral osteoporotic fractures
      by 33% (relative risk [RR] = 0.67; 95% CI 0.47, 0.97; p = 0.03). However, the 100
      and 400 IU/day dosages did not significantly reduce vertebral fracture risk.
      Effects on nonvertebral fractures were not significant (RR = 0.80; 95% CI 0.59,
      1.09; p = 0.16). There is mounting evidence to show that calcitonin diminishes
      bone pain in osteoporotic vertebral fractures, which may have clinical utility in
      vertebral crush fracture syndrome. A recent study suggests that nasal salmon
      calcitonin appears to be a promising therapeutic approach for the treatment of
      men with idiopathic osteoporosis, although long-term trials are necessary to
      confirm these results and evaluate fracture rate as an endpoint in men. The role
      of calcitonin in corticosteroid-induced osteoporosis remains controversial, hence
      it can only be considered a second-line agent for the treatment of patients with
      low bone mineral density who are receiving long-term corticosteroid therapy.

PMID- 15743108
TI  - Evidence-based endocrinology: how far have we come?
AB  - Evidence-based medicine is the judicious, conscientious, and explicit use of the
      best available evidence from clinical research in making clinical decisions. This
      definition recognizes a hierarchy of evidence that arranges study designs by
      their susceptibility to bias. The top of the hierarchy includes n-of-1 trials,
      systematic reviews of randomized trials, and single randomized trials reporting
      patient-important outcomes. The bottom of the hierarchy includes physiologic
      studies and unsystematic clinical observations. The definition posits that
      evidence alone is never enough to guide clinical decisions. In addition to
      evidence from clinical research, decision making requires careful and expert
      assessment of the patient's circumstances and elicitation of the patient's values
      and preferences. The latter should drive decisions, particularly when the trade
      offs (of benefit and risk) are close or unclear. The evidence-based medicine
      process involves: (i) asking an answerable question; (ii) acquiring the best
      available evidence; (iii) appraising the evidence to judge the strength of
      inference of its results; and (iv) applying the results to the individual
      patient. Evidence-based endocrinology is hindered by limited high-level evidence
      assessing patient-important outcomes, limited systematic summaries of this
      evidence, lack of time, and lack of systematic training of endocrinologists in
      evidence-based medicine. Current endocrine practice may require a redesign to
      enhance the role of endocrinologists as information brokers for colleagues and
      patients. In the last 10 years, evidence-based medicine has matured as a
      philosophy of clinical care and medical education. An appraisal of its role in
      endocrinology awaits the pervasion of its principles into all of endocrine
      practice.

PMID- 15743109
TI  - Leptin as a potential treatment for obesity: progress to date.
AB  - Despite significant reductions in the consumption of dietary fat, the prevalence
      of obesity is steadily rising in western civilization. Of particular concern is
      the recent epidemic of childhood obesity, which is expected to increase the
      incidence of obesity-related disorders. The obese gene (ob) protein product
      leptin is a hormone that is secreted from adipocytes and functions to suppress
      appetite and increase energy expenditure. Leptin is an attractive candidate for
      the treatment of obesity as it is an endogenous protein and has been demonstrated
      to have potent effects on bodyweight and adiposity in rodents. Whereas leptin has
      been successfully used in the treatment of leptin-deficient obese patients,
      trials in hyperleptinemic obese patients have yielded variable results. Long
      acting leptins have been tried but with no greater success. Other strategies
      including the use of leptin analogs and other factors that bypass normal leptin
      delivery systems are being developed. Identifying the mechanisms at the molecular
      level by which leptin functions will create new avenues for pharmaceutical
      targeting to simulate the intracellular effects of leptin.

PMID- 15743110
TI  - Estrogen therapy in systemic lupus erythematosus.
AB  - Given the female preponderance of systemic lupus erythematosus (SLE) in humans,
      the adverse effects of female gender and sex hormones in murine lupus, and
      numerous reports (retrospective, often anecdotal and uncontrolled) that describe
      a temporal association between estrogen exposure and development or exacerbation
      of SLE, it is tempting to accept that estrogens and SLE simply do not mix. While
      there are valid concerns regarding the use of exogenous estrogens in women with
      SLE, there are also potential health benefits to be considered. Oral
      contraceptives (OCs) offer effective birth control and may be bone protective in
      corticosteroid-treated patients. Recent studies, albeit retrospective, suggest
      that OCs are well tolerated in patients with SLE. Several salutary effects of
      postmenopausal estrogens assume particular importance in SLE where the risks of
      osteoporosis, exaggerated by menopause (natural or cyclophosphamide-induced) and
      corticosteroids, are substantial. However, the results of the Women's Health
      Initiative trial significantly limit the use of hormone replacement therapy in
      the general population, and raise particular concern for SLE patients. Other
      exogenous hormones (clomifene, gonadotropins, gonadotropin-releasing hormones)
      may be used to elevate levels of endogenous estrogen and to stimulate ovulation
      in patients with diminished fertility. Patients with inactive or stable/moderate
      disease and at low risk for thrombosis may benefit from OCs and other hormonal
      therapies without a change in lupus activity. Large prospective, double-blind,
      placebo-controlled studies inclusive of all ethnic groups should provide the
      basis for more definitive recommendations.

PMID- 15743111
TI  - Practical management of type 1 diabetes mellitus in adolescent patients:
      challenges and goals.
AB  - Type 1 diabetes mellitus in adolescents presents diagnostic and management
      challenges. Diagnostically, the challenge is to distinguish type 1 from type 2
      diabetes. A thin adolescent in diabetic ketoacidosis is easily recognized as
      having type 1 diabetes. However, since obesity does not negate the presence of
      type 1 diabetes, it is appropriate to measure diabetes-related antibody, C
      peptide, and insulin levels in individuals who are thought to have type 2
      diabetes to ensure that they do not have type 1 or a mixed type of diabetes. The
      goals for the management of type 1 diabetes in adolescents are to (i) prevent
      diabetic ketoacidosis; (ii) prevent severe hypoglycemia; (iii) maintain normal
      growth and development; and (iv) prevent long-term diabetic complications. To
      prevent diabetic ketoacidosis, patients must take their insulin appropriately. To
      ensure that this happens, increased parental supervision, psychological
      counseling, or placement in a different home environment may be necessary. All
      patients must be taught to appropriately manage sick days and test their urine
      for ketones when hyperglycemia is present. Prevention of severe hypoglycemia
      involves ensuring that the patient understands the symptoms of hypoglycemia and
      knows to test and treat it when the signs are present. Patients and families also
      need to know how to adjust insulin doses to prevent hypoglycemia and how to
      manage exercise appropriately. Patients with hypoglycemic unawareness need to
      meticulously avoid hypoglycemia. To maintain normal growth and development,
      adolescents with type 1 diabetes must have the appropriate tools to effectively
      match their meals to their lifestyle and to avoid the increased weight gain
      associated with improved glycemic control without intentionally manipulating
      their insulin dose to lose weight. The Diabetes Control and Complications Trial
      demonstrated that improved glycemic control decreased the risk of long-term
      diabetic complications. The goals of treatment in this study should be the goals
      for all adolescents with type 1 diabetes. To reach these goals, home glucose
      monitoring is critical. Patients need to know how to adjust insulin to maintain
      glucose levels in the range of 70-120 mg/dL (3.9-6.7 mmol/L) before meals.
      Insulin regimens need to be individually tailored to meet each patient's needs.
      Patients should be followed in a clinic using a multidisciplinary team approach
      at least every 3 months. Glycosylated hemoglobin should be measured at each
      visit. Regular eye exams, blood pressure monitoring, and urinary microalbumin
      measurements are critical. In this manner, the goals of management of type 1
      diabetes in adolescents can be met.

PMID- 15743112
TI  - The role of antioxidant micronutrients in the prevention of diabetic
      complications.
AB  - Diabetes mellitus is associated with an increased production of reactive oxygen
      species and a reduction in antioxidant defenses. This leads to oxidative stress,
      which is partly responsible for diabetic complications. Tight glycemic control is
      the most effective way of preventing or decreasing these complications.
      Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in
      patients with diabetes. Indeed, some minerals and vitamins are able to indirectly
      participate in the reduction of oxidative stress in diabetic patients by
      improving glycemic control and/or are able to exert antioxidant activity. This
      article reviews the use of minerals (vanadium, chromium, magnesium, zinc,
      selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic
      acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide,
      riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a
      particular focus on the prevention of diabetic complications. Results show that
      dietary supplementation with micronutrients may be a complement to classical
      therapies for preventing and treating diabetic complications. Supplementation is
      expected to be more effective when a deficiency in these micronutrients exists.
      Nevertheless, many clinical studies have reported beneficial effects in
      individuals without deficiencies, although several of these studies were short
      term and had small sample sizes. However, a randomized, double-blind, placebo
      controlled, multicenter trial showed that thioctic acid at an oral dosage of 800
      mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2
      diabetic patients. Above all, individuals with diabetes should be educated about
      the importance of consuming adequate amounts of vitamins and minerals from
      natural food sources, within the constraints of recommended sugar and
      carbohydrate intake.

PMID- 15743113
TI  - Long-term outcome of growth hormone therapy in children and adolescents.
AB  - Growth hormone (GH) has been available for more than 4 decades for the treatment
      of GH deficiency. Initially, GH was extracted from the pituitary glands of human
      cadavers, but its use was discontinued following the transmission of the
      Creutzfeldt-Jakob virus. After the development of recombinant GH (somatropin) in
      1985, an 'unlimited' commercial source of GH has been available, allowing for the
      treatment of a large number of short GH-deficient and -sufficient children.
      Refinements in both the dosage and the frequency of administration of GH have
      allowed GH-deficient children to reach nearly normal final heights, although
      mostly they are still below their target heights. Decreased bone mineral
      densities and increased concentrations of fasting and postprandial lipids,
      coagulation factors, and several independent cardiovascular risk factors have
      been reported in GH-deficient children and adolescents and appear to improve with
      GH administration. The short-term administration of GH to mostly non-GH-deficient
      short children with Turner syndrome, chronic renal insufficiency (CRI),
      intrauterine growth retardation (IUGR), and idiopathic short stature (ISS) has
      resulted in increased growth velocities. In addition, the final height of
      patients with Turner syndrome and CRI appears to improve with the long-term
      administration of GH. Final height data are still lacking in adolescents with
      IUGR, but height standard deviation score and final height predictions appear to
      improve with therapy. Based on the incomplete and inconclusive available data,
      one must conclude that GH treatment of children with ISS cannot be advised. The
      use of GH at replacement doses in children with GH deficiency has resulted in
      rare and generally reversible adverse effects. The long-term administration of
      pharmacologic GH doses to short, mostly non-GH-deficient children must, however,
      still be viewed with caution, as long-term complications cannot as yet be fully
      evaluated. GH therapy must be individualized and should be limited only to
      children with severe short stature or a significantly decreased growth velocity,
      to children under considerable stress due to their short stature, and to patients
      in whom low GH or low insulin-like growth factor-1 secretion might be the rate
      limiting factors for growth. The cost of the medication and the inconvenience of
      daily GH injections to otherwise mostly healthy short children must also be taken
      into account.

PMID- 15743114
TI  - To row for gold. From Ground Zero to Athens.

PMID- 15743116
TI  - Suprise 'em with sound (but don't fool yourself).

PMID- 15743115
TI  - Washington, Jefferson & EMS too. I: Charles Town, WV.

PMID- 15743117
TI  - Check your fabric.

PMID- 15743118
TI  - Moving day: how much is too much?

PMID- 15743119
TI  - Doug Wolfberg on EMS legal issues.

PMID- 15743120
TI  - A call to the hall.

PMID- 15743121
TI  - What the people say: fielding and responding to customer complaints.

PMID- 15743122
TI  - Are you prepared for the difficult airway?

PMID- 15743123
TI  - Transport ventilators: a guide for critical-care transportation, aeromedical &
      prehospital operations.

PMID- 15743124
TI  - Differentiating causes of respiratory distress.
AB  - Respiratory emergencies will continue to make up a large percentage of our EMS
      calls. Many of these conditions will be managed in the same fashion early on with
      a focus on oxygenation and adequate ventilation. Once the ABCs have been
      stabilized, use your assessment skills to create a differential diagnosis for
      respiratory distress. Once a field impression has been made, you can better
      direct a specific treatment. As always, follow your local treatment protocols
      established by your medical director. Practice your assessment skills and attend
      as much training as you can on airway and respiratory emergencies.

PMID- 15743125
TI  - Name that tune: an introduction to auscultating, differentiating and assessing
      lung sounds.

PMID- 15743126
TI  - "Is there a doctor in the house?" Addressing bystander physician involvement on
      scene.

PMID- 15743127
TI  - Driving like dorks: why are we killing ourselves?

PMID- 15743128
TI  - Spit and polish: paramedic uniform care.

PMID- 15743129
TI  - [Evidence-based medical education on the way. Not easy to find result measures,
      but good measurement techniques do exist].

PMID- 15743130
TI  - [Disaster planning--lessons learned from the fire disaster in Gothenburg].
AB  - The tragic fire disaster in Sweden 1998, killing 63 and wounding 213 teenagers
      was the result of arson fire in the basement of an overcrowded discotheque. Since
      the disaster occurred in a major city with substantial resources, all the injured
      could be hospitalised within two hours. The load on four local hospitals was
      initially severe due to the large number of injured. The patients suffered from
      inhalation injuries of different severity, whereas 25 of them also had deep skin
      burn injuries. Thirteen of the most severe burn injuries were transported to burn
      units in other parts of Sweden and to Norway. The vast psychosocial
      rehabilitation program initiated by health care staff, religious communions,
      schools and the community, has continued over the past years. This fire disaster
      emphasises the need for extensive preparation not only in the rescue and medical
      services, but also in many other areas of society.

PMID- 15743131
TI  - [Increased number of cancer cases following computer tomography in children.
      Radiation dosage--and cancer risk--can be reduced].

PMID- 15743132
TI  - [Doulas are necessary!].

PMID- 15743134
TI  - [Quality and shortages of patient safety--how reduce the costs?].
AB  - There is a sizable "poor quality and safety" problem in health care, not only in
      terms of suffering to patients but also in economic terms. Few studies have
      assigned costs to the problems. Decisions about whether to take action and which
      actions to take would be assisted by economic evidence. The article presents
      research which shows subjects and services where there is evidence both of poor
      quality and of effective interventions The article shows ways systematically to
      incorporate economic considerations into decisions about improvement and
      practical methods for estimating the costs of a quality problem and possible
      savings. A simple method is presented which would allow a purchaser or provider
      to make a comprehensive overview of a range of healthcare problems to help decide
      where to invest resources to save costs. Economic criteria and estimates,
      however, should not be the only criteria for selecting improvement subjects.
      Understanding of the costs of both the problem and the solution would encourage
      more effective quality and safety improvement and provide one way of measuring
      the progress of an action to solve the problem.

PMID- 15743133
TI  - [Selective reporting--greater problem than selective publishing?].

PMID- 15743135
TI  - [Mozart's musical physicians].

PMID- 15743136
TI  - [Four lethal injections resulted in Lex Maria].

PMID- 15743137
TI  - [Lack of Swedish well-functioning disaster planning is inexcusable].

PMID- 15743138
TI  - [SOS International's work in Thailand: all high-priority patients were selected
      for air transport home on New Year's Eve].

PMID- 15743139
TI  - [MSF and Sylt express out-of-date views about leadership in health care!].

PMID- 15743140
TI  - [Is Dutch euthanasia really on the inclined plane?].

PMID- 15743141
TI  - [I should strongly recommend ultrasound-guided biopsy].

PMID- 15743142
TI  - [Prescription for fewer sick-listings].

PMID- 15743143
TI  - [SBU's statement makes possible a sensible discussion about the role of salt for
      public health].

PMID- 15743144
TI  - The laboratory's role in assisted reproduction.

PMID- 15743145
TI  - No mercy for MRSA: treatment alternatives to vancomycin and linezolid.

PMID- 15743146
TI  - CLIA 2003's new concept: equivalent quality control.

PMID- 15743147
TI  - From lab tragedy to industry reaffirmation: a perilous journey.

PMID- 15743148
TI  - Medical-necessity determinations begin in the lab.

PMID- 15743149
TI  - Bortezomib therapy following first relapse.

PMID- 15743150
TI  - Integrating hormonal therapy with external-beam radiation and brachytherapy for
      prostate cancer.
AB  - The use of hormonal therapy with external-beam radiation (EBRT) to treat prostate
      cancer is a topic that has been well explored. The potential use of hormonal
      therapy and brachytherapy in the treatment of prostate cancer, however, continues
      to be controversial. This review is based on our current interpretation of the
      available literature assessing the outcomes of patients treated with EBRT and
      brachytherapy with or without hormonal therapy. Extrapolating from the findings
      of the Radiation Therapy Oncology Group (RTOG) 9413 trial, there appears to be a
      favorable interaction between hormonal therapy and irradiation in the lymph
      nodes. The benefits demonstrated with whole-pelvic EBRT and hormonal therapy are
      likely to extend to patients treated with brachytherapy as well. Studies suggest
      that the role of hormonal therapy in brachytherapy is limited without the
      application of whole-pelvic EBRT due to the inability of brachytherapy to address
      potential lymph nodes at risk. The potential role of hormonal therapy in
      conjunction with brachytherapy without pelvic radiotherapy, is limited by
      inconclusive data and abbreviated follow-up times.

PMID- 15743152
TI  - Clinical trials referral resource.

PMID- 15743151
TI  - Small-cell lung cancer: current therapy and novel agents.
AB  - Among patients with lung cancer, approximately 15% have small-cell lung cancer
      (SCLC). Although, without therapy, untreated SCLC is a rapidly proliferating
      tumor with a poor prognosis, response rates to chemotherapy and radiotherapy are
      high. SCLC is usually staged as either limited disease or extensive disease.
      Extensive disease is treated primarily with chemotherapy. A recent Japanese
      randomized trial compared IP (irinotecan [Camptosar]/cisplatin [Platinol]) with
      EP (etoposide/cisplatin). Patients in the IP arm had significantly better
      outcomes than patients in the EP arm. In the IP arm, the response rate was 84%,
      and the median overall survival period was 12.8 months. Limited disease is
      usually treated with concurrent chemotherapy and accelerated radiation therapy,
      and approximately 20% of patients are cured. Further investigations to improve
      local control and inhibit distant metastasis are clearly warranted. The dose-rate
      escalation in radiotherapy (administered concurrently with chemotherapy) is
      important in improving local control, and the introduction of molecular-targeting
      agents is necessary to inhibit distant metastasis.

PMID- 15743153
TI  - Early detection and treatment of spinal cord compression.
AB  - Several key areas must be considered in the diagnosis and management of spinal
      cord compression. Because the outcome can be devastating, a diagnosis must be
      made early and treatment initiated promptly. Although any malignancy can
      metastasize to the spine, clinicians should be aware that this occurs more
      commonly in certain diseases, i.e., lung cancer, breast cancer, prostate cancer,
      and myeloma. The current algorithm for early diagnosis of spinal cord compression
      involves neurologic assessment and magnetic resonance imaging of the entire
      spine. Treatment generally consists of intravenous dexamethasone followed by oral
      dosing. Depending on the extent of the metastases, symptoms may also be managed
      with nonnarcotic pain medicines, anti-inflammatory medications, and/or
      bisphosphonates, with local radiation administered as needed. Surgery has often
      led to destabilization of the spine.

PMID- 15743154
TI  - Melanoma vaccines: what we know so far.
AB  - Vaccines are a promising but still experimental treatment for melanoma. They are
      intended to stimulate immune responses against melanoma and by so doing, increase
      resistance against and slow the progression of this cancer. Key requirements for
      vaccines to be effective are that they contain antigens that can stimulate tumor
      protective immune responses and that some of these antigens are present on the
      tumor to be treated. Unfortunately, these antigens are still not known. To
      circumvent this problem, polyvalent vaccines can be constructed containing a
      broad array of melanoma-associated antigens. Several strategies are available to
      construct such polyvalent vaccines; each has advantages and disadvantages.
      Clinical trials have shown that vaccines are safe to use and have much less
      toxicity than current therapy for melanoma. Vaccines can stimulate both antibody
      and T-cell responses against melanoma, with the type of response induced, its
      frequency, and its magnitude depending on the vaccine and the adjuvant agent
      used. A growing body of evidence suggests that vaccines can be clinically
      effective. This evidence includes correlations between vaccine-induced antibody
      or T-cell responses and improved clinical outcome, clearance of melanoma markers
      from the circulation, improved survival compared to historical controls, and most
      convincingly, two randomized trials in which the recurrence-free survival of
      vaccine-treated patients was significantly longer than that of control groups.

PMID- 15743155
TI  - [Prevention and patient's compliance. Two key factors to deal with non
      communicable chronic diseases].
AB  - Over 50% of adults in Chile have a high cardiovascular risk. Thus, non
      communicable chronic diseases may surpass the capacity of the health systems.
      Therefore the prevention and treatment of their risk factors is urgent.
      Unfortunately, the low patient's compliance with prescribed treatment, reduces
      their efficacy. The best interventions to improve compliance with chronic
      treatment programs are: to simplify daily doses of medications and to do complex
      behavioral interventions. Risk factor prevention is a highly recommended action
      that has obtained promising results in Chile with the program "Mirame". To modify
      health behavior is also necessary to give people more power in their own care and
      to increase behavioral and social science contents into medical curricula.

PMID- 15743156
TI  - [Evaluation of a nutritional intervention to reduce cholesterol levels in
      patients with coronary artery disease].
AB  - BACKGROUND: The mainstay of cholesterol reduction therapy is the diet. But the
      lack of compliance and prescription problems limit its usefulness. AIM: To
      compare the effectiveness of a nutritional intervention given by a nutritionist
      with the usual recommendations given by a physician to reduce the LDL cholesterol
      levels in patients with coronary artery disease, treated at the Regional public
      hospital in Temuco. MATERIAL AND METHODS: One hundred and forty patients with
      coronary heart disease (last acute episode at least three months before), without
      nutritional interventions nor cholesterol-lowering drugs, who gave informed
      consent, were randomized to receive either instructions by their physician or to
      take part in a nutritional program. The nutritional intervention consisted in
      five educational sessions, adapted from the NCEP and from a program of the
      Nutrition Department of the Catholic University of Chile. Patients randomized to
      the medical intervention received the standard written recommendations about
      diet. Lipid profile was measured before the intervention and after a three and
      twelve months follow up. RESULTS: After one year the group on the
      nutritionalprogram reduced LDL cholesterol by 11.1% (p=0.03). There were no
      changes in the medical group. However, only 10% patients on the nutritional
      intervention group and 8% of those with medical recommendations achieved LDL
      cholesterol levels less than 100 mg/dl. There were no changes in triglycerides,
      weight or body mass index during the period. CONCLUSIONS: Although this
      nutritional intervention proved to be more effective than usual medical
      instructions, most patients on secondary prevention did not achieve acceptable
      LDL cholesterol levels.

PMID- 15743157
TI  - [Primary thrombophilia. Report of 93 cases and 12 asymptomatic relatives].
AB  - BACKGROUND: Thrombophilia is defined as an altered hemostasis that predisposes to
      thrombosis. It can be primary when there is a family clustering of the disease or
      secondary, when it is associated to an acquired risk factor. AIM: To report
      clinical features in a series of patients with primary thrombophilia. MATERIAL
      AND METHODS: Review of clinical records of patients with thrombotic episodes that
      lead to the suspicions of primary thrombophilia. Analysis of asymptomatic adult
      close relatives of these patients. RESULTS: We report 93 subjects (56 females,
      age range 14-77 years) with repeated episodes of thrombosis and a family history
      of thrombosis and 12 asymptomatic close relatives. Seventy one percent had the
      first thrombotic episode before the age of 40 years, 62% had more than one
      thrombotic episode and 37% had a family history of thrombosis. Twenty four
      percent had protein C deficiency, 24% had antithrombin III deficiency, 18% had
      resistance to activated C protein by factor V Leiden, 10% had protein S
      deficiency, and 10% had the G20210 mutation of prothrombin gene. Among acquired
      defects studied simultaneously, 30% had lupus anticoagulant and 11% had
      hyperhomocysteinemia. Twenty four percent of cases had more than one
      thrombophilic risk factor. Among asymptomatic relatives, five had factor V
      Leiden, four had protein C deficiency and three had the G20210 mutation of
      prothrombin gene. CONCLUSIONS: Thrombophilia must be suspected in young subjects
      with thrombotic episodes and a family history. The type of coagulation defect
      will determine prognosis, and the type of treatment.

PMID- 15743159
TI  - [Height of pregnant women attended in the public and private health systems in
      Chile].
AB  - BACKGROUND: Adult height has increased around the world, especially in developed
      countries, probably due to the improvement in life conditions. AIM: To assess
      differences in women's height in two population samples of different
      socioeconomic status coming from the public and the private health system in
      Chile, and the influence of the year of birth on height. MATERIAL AND METHODS:
      Data from 5,416 pregnant women attended in the public health system and 1,658
      women attended in the private system, were analyzed. Among women attended in the
      private system, the association of maternal height with anthropometric indices of
      the newborn were also studied. RESULTS: Mean height difference in the two systems
      reached 3.78 cm. The correlation coefficient of maternal height and year of birth
      was significant although weak in the two health systems, but mean height
      differences between decades of birth were significant only in the public sector:
      0.7 and 1 cm in each of the two most recent decades. Association of maternal
      height was significant although weak, with both weight and height at birth,
      controlling for newborn's sex. CONCLUSIONS: Socioeconomic factors influence
      maternal height. Maternal height has an influence on fetal growth.

PMID- 15743158
TI  - [P450Arom and estrogenic microenvironment of eutopic endometria in
      endometriosis].
AB  - BACKGROUND: Endometriosis, a common gynecologic disorder characterized by
      endometrial glands and stroma outside the uterus, is diagnosed by direct
      visualization of peritoneal and ovarian implants during laparoscopy. AIM: To
      study the estrogenic microenvironment in eutopic endometria of women with and
      without endometriosis. PATIENTS AND METHODS: Eutopic endometria, obtained during
      laparoscopy from 23 women with endometriosis and 20 fertile cyclic women
      undergoing tubal sterilization, was studied. P450Arom mRNA expression (RT-PCR)
      was measured. Also, P450Arom activity was assessed measuring testosterone
      conversion to estradiol and the concentration of this last hormone in cultured
      endometrial explants. RESULTS: Age and body mass index was similar in both groups
      studied. Seventy nine percent of endometria from women with endometriosis and in
      29.4% from control group expressed P450Arom mRNA (p <0.01). The intensity of the
      band was higher in secretory endometria from women with endometriosis when
      compared to controls (p <0.01), but it was similar during the proliferative
      phase. Estradiol secretion to the culture media by proliferative endometria
      explants from women with endometriosis was 3-fold higher than secretory
      endometria (p <0.01) and endometria from control women in both phases. P450Arom
      activity, in the presence of testosterone, was 7-fold higher in endometrial
      cultures from women with endometriosis, when compare with the basal culture (p
      <0.01). However, in endometrial explant cultures from control women, this
      activity was not statistical different. CONCLUSIONS: These results indicate that
      in women with endometriosis, the microenvironment in the endometria is estrogenic
      as a consequence of an increased expression and activity of the P450Arom.

PMID- 15743160
TI  - [Detection of bone marrow micrometastases in patients with gallbladder cancer].
AB  - BACKGROUND: There is a very strong documented correlation between the appearance
      of cancer cells in blood and occurrence of metastasis in gastrointestinal cancer.
      AIM: To determine MUC1, CK19, CK20 and CEA mRNA expression in bone marrow of
      patients with gallbladder cancer and evaluate its clinical significance. MATERIAL
      AND METHODS: Sixty eight samples were analyzed, 38 bone marrow samples of
      gallbladder cancer patients, 20 healthy donors, and 10 frozen samples of
      gallbladder cancer. Nested reverse transcriptase-polymerase chain reaction
      (nested RT-PCR) was used to analyze mRNA expression. RESULTS: All frozen tumors
      were positive for CEA, CK19, and MUC1 mRNA and 70% were positive for CK20.
      Seventeen of 20 donor samples were positive for MUC1 and only one sample from
      donors was positive for both CK20 and CK19 mRNA. Among the 38 blood and bone
      marrow samples of gallbladder cancer patients, the expression of MUC1, CK19,
      CK20, and CEA, mRNA was 60.5% (23/38), 31.6% (12/38), 7.9% (3/38), and 7.9%
      (3/38), respectively. Disregarding the MUC1 results. 37% (14/38), 13% (5/38) and
      5% (2/38) were positive for one, two and three markers respectively. Not
      significant differences were found in survival with a follow up to 12 months.
      CONCLUSION: Our results indicate that the molecular detection of tumor cells in
      bone marrow in patients with gallbladder carcinoma is technically possible, being
      CEA, CK19 and CK20 gene expression the best markers. The MUC1 gene expression
      marker was highly unspecific and it should not been considered. The detection of
      bone marrow micrometastasis might be helpful in prognosis and the selection of
      clinical treatment but a larger series with a longer follow-up should be studied.

PMID- 15743161
TI  - [Child battering and adult psychopathology: an empiric study].
AB  - BACKGROUND: Childhood trauma and battering have been associated with adult
      psychopathology. AIM: To explore the relationship between childhood trauma,
      somatization, post traumatic stress disorder (PTSD), affective disorder and
      borderline personality disorder in hospitalized patients of four Chilean
      hospitals. MATERIAL AND METHODS: Five hundred five patients were screened by a
      short seven item trauma recollection scale (70 from San Bernardo Hospital, 193
      from Salvador Hospital, 97 from El Trabajador Hospital and 147 from Curico
      Hospital). A random sample of 85 cases was studied in depth using the CIDI 2.1,
      depression, PTSD and somatization scales, Inventory of Personality Organization
      (IPO) and the OQ 45.2 scale. RESULTS: Forty five percent of patients did not
      report traumatic experiences, 38.4% recalled one or two events and 16.3% three or
      more traumatic experiences. The most remembered event was physical punishment
      (28.7%), followed by traumatic separation from parents (27.1%), alcohol and drug
      use by an adult at home (22%) and presence of family violence (22%). Thirty two
      percent of the 85 selected cases met CIDI criteria for affective disorder, 20%
      for post traumatic stress disorder and 11.8% for somatization disorder. There
      were statistically significant correlations between the frequence of trauma and
      post traumatic stress disorder (p <0.001), as well as somatization and depressive
      disorder (p <0.007 and 0.008). CONCLUSIONS: This study supports the concept that
      traumatic psychosocial environments during childhood are a risk factor for
      diverse psychiatric syndromes during adulthood.

PMID- 15743162
TI  - [Acute abdomen in the elderly].
AB  - BACKGROUND: Nearly 10% of emergency consultations are due to acute abdominal
      pain. In people over 65 years old, it can have atypical presentations, that
      retard the correct diagnosis and worsens prognosis. AIM: To study the causes,
      evolution and prognosis of acute abdomen in the elderly. MATERIAL AND METHODS:
      Prospective study of 45 patients aged more than 65 years old (mean age+/-SD,
      75.7+/-7.7, 51% men) and 221 patients of less than 65 years old (mean age+/-SD,
      36.7+/-14.0, 48% men), consulting for acute abdomen in the emergency room.
      RESULTS: Sixty six percent of elderly patients had concomitant diseases, that
      were multiple in 63%. In this age group, the causes accounting for 71% of acute
      abdominal pain were bilio-pancreatic diseases (31.1%), intestinal adhesive
      obstruction (17.7%), complicated abdominal wall hernia (13.7%), and complications
      of peptic ulcer disease (8.9%). Sixty four percent required surgical treatment
      and, in almost 50% the surgical risk was classified in ASA III or IV, according
      to the American Society of Anesthesiology. Thirty one percent had postoperative
      complications. Compared with their younger counterparts, elderly patients
      required significantly (p<0.05) more admissions to intensive care units (2.7 and
      24.2% respectively), more connections to mechanical ventilation (1.4 and 8.9%
      respectively) and longer hospital stays (5.4+/-7.4 and 12.4+/-10.9 days,
      respectively). In this series overall mortality was 6.7%, being 0.6% for young
      patients and 11.1% for the surgical group over 65 years old. CONCLUSIONS: Acute
      abdomen in the elderly has a high rate of complications and mortality. According
      to the causes of acute abdomen in this group, evaluation in the emergency setting
      with an ultrasonography may be very useful. In the elderly, elective correction
      of potential causes of acute abdomen should be done.

PMID- 15743163
TI  - Lack of mutation in exon 10 of p53 gene in thyroid tumors.

PMID- 15743164
TI  - [Hepatocellular carcinoma with cardiovascular invasion. Report of five cases].
AB  - The diagnosis of hepatocellular carcinoma in cirrhotic patients has increased,
      mainly due to early detection using newer imaging techniques. The therapeutic
      approach depends on the tumor staging and the liver function. Cardiac involvement
      has a very bad prognosis. We report three males aged 59, 75 and 76 years and two
      females, aged 64 and 79 years. All had cirrhosis of diverse aetiologies with
      hepatocellular carcinoma and tumoral invasion of the inferior vena cava and right
      atrium. Three patients died during hospital stay and two were discharged for
      conservative management at home. This rare complication has to be considered in
      cirrhosis.

PMID- 15743165
TI  - [Temporal crescent syndrome. Report of a case and review of the literature].
AB  - The temporal crescent syndrome or half-moon syndrome is a rare mono ocular
      retrochiasmatic visual field defect that can be correlated to a lesion along the
      contralateral parieto-occipital sulcus. This field defect may be missed in
      automated perimetry. We report a 45 year old man, consulting for sudden loss of
      the peripheral temporal field in his right eye. The magnetic resonance imaging
      and the spectroscopy studies confirmed an ischemic lesion on the left anterior
      occipital cortex. Control imaging studies six months later did not show changes
      in the lesion.

PMID- 15743167
TI  - [Indices of public health services and resource allocation from the Health
      Ministry of Chile].
AB  - BACKGROUND: Chile has a National Health Services System, formed by 29 Health
      Services. An efficient resource distribution among this services is crucial for
      an efficient health care delivery. AIM: To obtain indices from the Chilean Public
      Health Services, that could improve allocation of resources. MATERIAL AND
      METHODS: Information from the Chilean Public Health Services, corresponding to
      activities during 2001 budgetary period, was collected. This is the latest
      complete and official information for the totality of Health Services in the
      country. Seventeen variables generated or monitored by the Instituto Nacional de
      Estadisticas (INE), the Ministerio de Salud (MINSAL), the Ministerio de Hacienda,
      the Ministerio de Planificacion y Cooperacion (MIDEPLAN) and the Fondo Nacional
      de Salud (FONASA) were studied. The Main Components Analysis (ACP) was used,
      obtained from the R correlation matrix. RESULTS: The first two main components
      were selected, with an accumulated percentage of explained variability of 63.05%.
      The first component is related to the population assigned to each Health Service.
      This corresponds to the number of people needed to treat in the hospitals of
      these Services and their answer to this demand, justified by the expenses in
      which each Health Service incurs. There is an inverse relation of the first
      component with health indicators, measured by burden of disease and death. The
      second main component would represent the social and economic characteristics of
      the population, poor and very poor populations and public health insurance
      beneficiaries, to take care of in each Health Service. CONCLUSIONS: Health
      indicators in each Health Service are not considered a priority for resource
      distribution among Health Services in the country. The transference is done
      considering the indices contained in the two main components defined.

PMID- 15743168
TI  - [The evolution of Chilean universities from 1981 to 2004].
AB  - In 1981, a supreme decree allowed the creation of private universities in Chile.
      As a consequence, 50 new universities were created in one decade, under the
      surveillance of the Council for Superior Education. This paper analyzes the
      evolution of this expansion process, that resulted in an admission of 370,000
      students to 60 universities along the country, during 2004. At the moment, 42% of
      the universities, designed as traditional, receive state financing and 58% are
      private. Twenty six percent are owned by the state, 52% are secular and 22% are
      confessional. The 25 traditional universities are complex organizations of a high
      academic level. New private universities are only devoted to teaching and some
      have obtained their autonomy. Some have improved the quality of their academic
      staff, perform research and impart doctorate degrees. However, most are small and
      with a limited academic staff. Traditional universities are stratified in a
      superior level. Eight private universities and some regional institutions, that
      are becoming complex and performing research activities, are stratified in a
      middle level. Two thirds of the private universities are in the lower level. The
      expansion of superior education is a sign of the social and cultural progress
      that Chile has experienced.

PMID- 15743166
TI  - [Pseudohypoparathyroidism or vitamin D deficiency? Report of one case].
AB  - Pseudohypoparathyroidism is characterized by a resistance to parathormone, with
      variable phenotypical and biochemical manifestations. Its diagnosis is difficult.
      We report a 28 year old male presenting with a hypokalemic periodic paralysis.
      His serum PTH was elevated to 1,343 and 1,101 pg/ml with concomitant hypocalcemia
      of 7.9 and 6.7 mg/dl. Twenty four hour urinary calcium and serum 25 hydroxy
      vitamin D were normal. Bone mineral density was normal. The patient was managed
      with calcitriol in doses of 1 to 2 microg/d, associated to calcium 2 g/day. Serum
      calcium levels and PTH normalized after two months and six months of treatment
      respectively.

PMID- 15743169
TI  - [Bioethics on the couch: can Freud help us to deal with the uncertainties of
      medical ethics?].
AB  - Only recently, bioethics has crystallized into a full-fledged discipline. The aim
      of this article is to analyze whether Freud is competent to deal with bioethics.
      Freudian psychoanalysis is reviewed as a global theory that touches culture as a
      totality. And it is by way of a global theory of culture that Freud takes up the
      phenomenon of morality. Freud gives not an alternative answer to unchanged
      questions in bioethics, but delivers a new manner of asking moral questions. The
      ground rule establishes the conditions for treatment. And secondly, it is a
      radical elimination of any position of moral existence. Ethics is simply
      bracketed (put in parenthesis) in the sense that in its regard no position is
      taken either for or against. What is at stake is self-recognition and Freudian
      itinerary runs from misunderstanding to recognition. If Freud offers a technique,
      it is not included in the cycle of techniques of domination; it is a technique of
      veracity.

PMID- 15743170
TI  - [Intention to treat and follow up are important in assessing validity of a
      randomized clinical trial].

PMID- 15743171
TI  - [Morphine in acute pancreatitis?].

PMID- 15743172
TI  - New approaches toward anti-HIV chemotherapy.

PMID- 15743173
TI  - Development and preliminary optimization of indole-N-acetamide inhibitors of
      hepatitis C virus NS5B polymerase.
AB  - Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA
      polymerase enzyme has recently emerged as a viable strategy toward blocking
      replication of viral RNA in cell-based systems. We report here a novel class of
      allosteric inhibitor of NS5B that shows potent affinity for the NS5B enzyme and
      effective inhibition of subgenomic HCV RNA replication in HUH-7 cells. Inhibitors
      from this class have promising characteristics for further development as anti
      HCV agents.

PMID- 15743174
TI  - Identification of 2-(4-benzyloxyphenyl)-N- [1-(2-pyrrolidin-1-yl-ethyl)-1H
      indazol-6-yl]acetamide, an orally efficacious melanin-concentrating hormone
      receptor 1 antagonist for the treatment of obesity.
AB  - Optimization of a high-throughput screening hit against melanin-concentrating
      hormone receptor 1 (MCHr1) led to the discovery of 2-(4-benzyloxy-phenyl)-N-[1-(2
      pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide (7a). This compound was found to
      be a high-affinity ligand for MCHr1 and a potent inhibitor of MCH-mediated Ca(2+)
      release, showed good plasma and CNS exposure upon oral dosing in diet-induced
      obese mice, and is the first reported MCHr1 antagonist that is efficacious upon
      oral dosing in a chronic model of weight loss.

PMID- 15743175
TI  - Synthesis of NO-donor bisphosphonates and their in-vitro action on bone
      resorption.
AB  - A new class of bisphosphonates containing nitrooxy NO-donor functions has been
      developed. The products proved to display affinity for hydroxyapatite. Injection
      of (99m)Tc-labeled derivatives 11 and 18 into male rats showed a preferential
      accumulation of the compounds in bone as compared to blood and muscles. The
      products were found to inhibit the differentiation of pre-osteoclasts to
      functional osteoclasts induced by receptor activator of NF-kappaB ligand (RANKL),
      through a prevalent NO-dependent mechanism.

PMID- 15743176
TI  - Solid-phase total synthesis of kahalalide A and related analogues.
AB  - The marine natural product kahalalide A, a cyclic depsipeptide, was prepared by
      total synthesis on solid-phase. A backbone cyclization strategy was followed,
      using the Kenner sulfonamide safety-catch linker. By NMR comparison of synthetic
      and naturally isolated material, the stereochemistry of the methylbutyrate side
      chain was established as (S). Several analogues were synthesized and tested for
      antimycobacterial activity. The results indicate that the alcohol functional
      group in the serine and threonine residues is important, while the methylbutyrate
      side chain can be replaced by an achiral hexanoate with an increase in activity.

PMID- 15743177
TI  - Synthesis and biological evaluation of meperidine analogues at monoamine
      transporters.
AB  - A series of aryl-substituted meperidine analogues was synthesized, and the
      binding affinities were determined at the DAT, SERT, and NET as well as at mu
      opioid receptors. Generally the analogues exhibited increased affinity for the
      DAT and SERT relative to meperidine but exhibited low binding affinity for the
      NET. The 2-naphthyl derivative 7f was the most potent ligand at the SERT (K(i) =
      0.0072 muM) and was the most selective ligand for the SERT over the DAT (DAT/SERT
      = 158) and mu-opioid receptors (mu/SERT = 281). The 3,4-dichlorophenyl derivative
      7e was the most potent ligand at the DAT (K(i) = 0.125 muM) and was the most
      selective ligand for the DAT over mu-opioid receptors (mu/DAT = 16.3) but
      remained slightly more selective for the SERT over the DAT(DAT/SERT = 6.68).
      Three compounds, the 3,4-dichlorophenyl derivative 7e and the 2-naphthyl
      analogues 6f and 7f, were identified that were more potent at the DAT than
      meperidine and that exhibited well-defined biphasic dopamine uptake inhibition
      similar to meperidine. However, none of the analogues tested produced locomotor
      effects or substituted for cocaine in drug discrimination studies, suggesting
      that the mu-opioid effects of these analogues may contribute to the poor efficacy
      observed in vivo.

PMID- 15743178
TI  - Design, synthesis, and in vitro evaluation of dipeptide-based antibody minor
      groove binder conjugates.
AB  - Antibody-drug conjugates (ADCs) were prepared consisting of DNA minor groove
      binder drugs (MGBs) attached to monoclonal antibodies (mAbs) through peptide
      linkers designed to release drugs inside the lysosomes of target cells. The site
      of linker attachment on the MGB was at the 5-position on the B-ring, since model
      studies showed that attachment of an electron-withdrawing group (i.e., acyl,
      carbamoyl) at this position increased the stability of the molecule. Because of
      the hydrophobic nature of the MGBs, several measures were required to overcome
      their tendencies to induce mAb aggregation upon conjugation. This is exemplified
      in the series of ADCs containing the amino-CBI drug 1. Initial adducts were
      prepared using the peptide sequence valine-citrulline, attached to a self
      immolative para-aminobenzyl carbamate spacer. The resulting ADCs were completely
      aggregated. Removal of the self-immolative spacer, introduction of a more
      hydrophilic valine-lysine sequence, and incorporation of a tetraethyleneglycol
      unit between the mAb and the peptide resulted in conjugates that were
      nonaggregated, even with as many as eight drugs per mAb. These results were
      extended to include the hydroxy aza-CBI drug 2, which was linked to the valine
      lysine sequence through a para-aminobenzyl ether self-immolative spacer. The
      resulting mAb conjugates were monomeric and released the hydroxy aza-CBI drug
      upon treatment with human cathepsin B. In vitro cytotoxicity assays established
      that the mAb-MGB drug conjugates were highly cytotoxic and effected
      immunologically specific cell kill at subsaturating doses. The results provide a
      general strategy for MGB prodrug design and illustrate the importance of linker
      hydrophilicity in making nonaggregated, active mAb-MGB conjugates.

PMID- 15743179
TI  - Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors:
      synthesis, structure-activity relationships, and antitumor activities of N-phenyl
      N'-{4-(4-quinolyloxy)phenyl}ureas.
AB  - N-Phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas were found to be a novel class of
      potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2)
      tyrosine kinase through synthetic modifications of a lead compound and structure
      activity relationship studies. A representative compound 6ab, termed Ki8751,
      inhibited VEGFR-2 phosphorylation at an IC(50) value of 0.90 nM, and also
      inhibited the PDGFR family members such as PDGFRalpha and c-Kit at 67 nM and 40
      nM, respectively. However, 6ab did not have any inhibitory activity against other
      kinases such as EGFR, HGFR, InsulinR and others even at 10000 nM. 6ab suppressed
      the growth of the VEGF-stimulated human umbilical vein endothelial cell (HUVEC)
      on a nanomolar level. 6ab showed significant antitumor activity against five
      human tumor xenografts such as GL07 (glioma), St-4 (stomach carcinoma), LC6 (lung
      carcinoma), DLD-1 (colon carcinoma) and A375 (melanoma) in nude mice and also
      showed complete tumor growth inhibition with the LC-6 xenograft in nude rats
      following oral administration once a day for 14 days at 5 mg/kg without any body
      weight loss.

PMID- 15743180
TI  - Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4
      triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit.
AB  - We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4
      triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the alpha(3)
      receptor subtype with 5-fold selectivity in binding affinity over alpha(1). This
      paper describes a detailed investigation of the substituents on this core
      structure at both the 3- and 6-positions. Despite evaluating a wide range of
      groups, the maximum selectivity that could be achieved in terms of affinity for
      the alpha(3) subtype over the alpha(1) subtype was 12-fold (for 57). Although
      most analogues showed no selectivity in terms of efficacy, some did show partial
      agonism at alpha(1) and antagonism at alpha(3) (e.g., 25 and 75). However, two
      analogues tested (93 and 96), both with triazole substituents in the 6-position,
      showed significantly higher efficacy for the alpha(3) subtype over the alpha(1)
      subtype. This was the first indication that selectivity in efficacy in the
      required direction could be achieved in this series.

PMID- 15743181
TI  - Design and synthesis of melanocortin peptides with candidacidal and anti-TNF
      alpha properties.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) is an endogenous
      antiinflammatory peptide with antimicrobial properties. We recently found that a
      synthetic analogue, [dNal(2')-7, Phe-12]-alpha-MSH (6-13), was considerably more
      potent in killing Candida albicans, but the anti-cytokine potential of the
      molecule was not investigated. Because molecules that combine candidacidal and
      antiinflammatory properties could be very useful in clinical practice, we
      measured the anti-TNF-alpha potential of [dNal(2')-7, Phe-12]-alpha-MSH (6-13)
      and explored effects of amino acid deletions and substitutions on both anti
      Candida and anti-TNF-alpha activities. The results show that anti-TNF-alpha
      properties of this candidacidal peptide are only marginally increased relative to
      the native sequence. Conversely, we found that a closely related candidacidal
      analogue, [dNal(2')-7, Pro-12]-alpha-MSH (6-13), had enhanced anti-TNF-alpha
      effects in vitro and in vivo. This peptide, and other melanocortins with a
      similar dual effect, could be very useful to eradicate infections and,
      concurrently, reduce inflammatory reactions.

PMID- 15743182
TI  - Synthesis of phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides: novel inhibitors
      of reverse transcriptase.
AB  - Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good
      yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse
      transcriptase inhibitory activity of the obtained compounds have been
      investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing
      low levels of cytotoxicity, exert a specific inhibitor activity on two different
      reverse transcriptases, which is comparable with that of AZT, opening new
      perspectives on their possible use as therapeutic agents, in anti-retroviral and
      anti-HBV chemotherapy.

PMID- 15743183
TI  - Beta-lactam screening by specific residues of the OmpF eyelet.
AB  - Beta-lactams use aqueous channels of porins to penetrate Gram-negative bacteria.
      The L3 loop of Escherichia coli OmpF porin is a key feature that actively
      contributes to both channel size and electrostatic properties. Acid residues
      D113, E117, and D121 are responsible for the negative part of the local
      electrostatic field on this loop. Two substitutions, D113A and D121A, located in
      the negatively charged cluster of the OmpF eyelet, increase the likelihood of
      producing bacteria susceptible to several beta-lactams. D113A substitution
      results in an increase in the ampicillin, cefoxitin, and ceftazidime
      susceptibility. Molecular modeling suggests that the charges harbored by the beta
      lactam molecules interact with the charged residues located inside the porin
      eyelet.

PMID- 15743184
TI  - Synthesis and biological evaluation of novel naphthocarbazoles as potential
      anticancer agents.
AB  - We report the efficient synthesis involving palladium-catalyzed reactions and
      biological evaluation of new naphthocarbazoles designed as potential anticancer
      agents. The use of 5- and 6-benzyloxyindoles generated three substitution sites
      which were successively exploited to introduce several hydrophilic side chains.
      The cytotoxicity of the newly designed compounds was evaluated on three cell
      lines. Several compounds showed a marked cytotoxicity with IC(50) values in the
      sub-micromolar range. This is the case for the 3-hydroxy
      naphthopyrrolocarbazoledione 37, bearing a dimethylaminoethyl side chain, which
      is extremely cytotoxic to L1210 and DU145 cells (IC(50): 36 nM, 108 nM) and
      induces an accumulation of L1210 cells in the G2+M phases of the cell cycle. Some
      of the most cytotoxic compounds were tested for inhibition of CDK-5, GSK-3 and
      topoisomerase I, and their interaction with DNA was also evaluated. Interaction
      with DNA was detected, suggesting that nucleic acids represent a privileged
      target for these molecules.

PMID- 15743185
TI  - Cationic polysaccharides as antiprion agents.
AB  - Cationic polysaccharides were synthesized by conjugation of various oligoamines
      to oxidized polysaccharides by reductive amination and tested for antiprion
      activity. Polycations of dextran, pullulan and arabinogalactan grafted with
      oligoamines of 2 to 4 amino groups were investigated for their ability to
      eliminate PrP(Sc), the protease-resistant isoform of the prion protein, from
      chronically infected neuroblastoma cells, ScN2a-M. The proteinase K (PK)
      resistant PrP elimination depends on both the concentration of the reagent and
      the duration of exposure. The most potent compound was found to be dextran
      spermine that caused depletion of PrP(Sc) to undetectable levels at concentration
      of 31 ng/mL after 4 days of exposure. Activity analysis revealed that grafted
      oligoamine indentity of the polycation plays a significant role in elimination of
      PK-resistant PrP from chronically infected N2a-M cells, regardless of the
      polysaccharide used. Dextran-spermine conjugates were modified with oleic acid
      and with methoxypoly(ethylene glycol) (MPEG) at various degrees of substitution
      for further studies and their antiprion activity was examined. Substitution of
      dextran-spermine with MPEG or oleic acid slightly decreases its activity as a
      function of MPEG/oleic acid content. These findings confirm previous reports that
      polycations are effective in eliminating PrP(Sc) in vitro.

PMID- 15743186
TI  - N- and C-terminal modifications of nociceptin/orphanin FQ generate highly potent
      NOP receptor ligands.
AB  - Previous structure-activity studies on nociceptin/orphanin FQ (N/OFQ) identified
      [Phe(1)Psi(CH(2)NH)Gly(2)]N/OFQ(1-13)-NH(2) and [Nphe(1)]N/OFQ(1-13)-NH(2) as a
      N/OFQ peptide receptor (NOP) partial agonist and pure antagonist, respectively.
      The addition of fluorine to the Phe(4) or the insertion of a further pair of
      basic amino acids Arg(14)-Lys(15) generate potent agonists. On the basis of these
      findings, we combined in the N/OFQ-NH(2) template the chemical modifications
      Arg(14)-Lys(15) and (pF)Phe(4) that increase the agonist potency with those
      conferring partial agonist (Phe(1)Psi(CH(2)NH)Gly(2)) or pure antagonist
      (Nphe(1)) properties. Twelve peptides were synthesized and pharmacologically
      evaluated in Chinese hamster ovary cells expressing the human recombinant NOP and
      in electrically stimulated mouse vas deferens and guinea pig ileum assays. All
      peptides behaved as NOP ligands; the chemical modifications Arg(14)-Lys(15) and
      (pF)Phe(4) increased ligand affinity/potency. Peptides with the normal Phe(1)
      Gly(2) peptide bond behaved as full agonists, and those with the
      Phe(1)Psi(CH(2)NH)Gly(2) modification behaved as partial agonists, while those
      with the Nphe(1) modification behaved as partial agonists or pure antagonists
      depending on the presence or absence of the (pF)Phe(4) modification,
      respectively. The full agonist [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2), the
      partial agonist [Phe(1)Psi(CH(2)NH)Gly(2),(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2),
      and the pure antagonist [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) represent the most
      potent peptide ligands for NOP.

PMID- 15743187
TI  - Nonpolar and short side chain groups at C-11beta of estradiol result in
      antiestrogens.
AB  - We have previously found that esters of 11beta-estradiol carboxylates are
      transformed from an estrogen into an antiestrogen when the 11beta-side chain is
      increased in length from four to five non-hydrogen atoms (n > or = 5). To
      understand the structural requirements for this transformation and obtain
      metabolically stable analogues that are not susceptible to esterase cleavage, we
      have synthesized other compounds having an 11beta-side chain composed of other
      functional groups: ketones, amides, ethers, and thiono esters. With the exception
      of amides, which bind poorly to the estrogen receptor (ER), all of these
      compounds exhibit antiestrogenic action when the side chain length is n > or = 5.
      Ethers (n > or = 5), studied in more detail, inhibit the action of estradiol with
      either ERalpha or ERbeta. In rat uteri they are estrogen antagonists/weak
      agonists and decrease the concentration of cholesterol in blood (an hepatic
      estrogenic action). Thus, these short chain and nonpolar 11beta-analogues of
      estradiol have tissue specific antiestrogenic/estrogenic actions, characteristics
      of selective estrogen receptor modulators.

PMID- 15743188
TI  - CoMFA and CoMSIA analyses of Pneumocystis carinii dihydrofolate reductase,
      Toxoplasma gondii dihydrofolate reductase, and rat liver dihydrofolate reductase.
AB  - In a continuing effort to develop potent and selective dihydrofolate reductase
      (DHFR) inhibitors against opportunistic pathogens, we developed three-dimensional
      quantitative structure-activity relationship (3D QSAR) models for the inhibitory
      activity against Pneumocystis carinii (pc) DHFR, Toxoplasma gondii (tg) DHFR, and
      rat liver DHFR, using a data set of 179 structurally diverse compounds. To ensure
      a balanced distribution of more potent and less potent drugs in the training set,
      three different 90-compound training sets taken from the main data set were used,
      one for each enzyme, while the remaining 89 compounds in the main data set in
      each case were used as the test set. Three methods, namely, conventional CoMFA,
      all orientation search (AOS) CoMFA, and CoMSIA were applied to the training sets.
      While the AOS CoMFA models gave the best internal predictions (cross-validated
      r(2) values from the training sets), which are satisfactory, CoMSIA models gave
      the best external predictions (predictive r(2) values from the test sets). Both
      AOS CoMFA and CoMSIA analyses were used to construct stdev*coefficient contour
      maps which can be used to design new compounds in an interactive fashion.

PMID- 15743189
TI  - Design and synthesis of a novel potent myelin basic protein epitope 87-99 cyclic
      analogue: enhanced stability and biological properties of mimics render them a
      potentially new class of immunomodulators.
AB  - A cyclic analogue, [cyclo(87-99)MBP(87)(-)(99)], of the human immunodominant
      MBP(87)(-)(99) epitope, was designed based on ROESY/NMR distance information and
      modeling data for linear epitope 87-99, taking into account T-cell (Phe(89),
      Lys(91), Pro(96)) and HLA (His(88), Phe(90), Ile(93)) contact side-chain
      information. The cyclic analogue was found to induce experimental allergic
      encephalomyelitis (EAE), to bind HLA-DR4, and to increase CD4 T-cell line
      proliferation, like that of the conformationally related linear MBP(87)(-)(99)
      epitope peptide. The mutant cyclic peptides, the cyclo(91-99)[Ala(96)]MBP(87)(
      )(99) and the cyclo(87-99)[Arg(91)Ala(96)]MBP(87)(-)(99), reported previously for
      suppressing, to a varying degree, autoimmune encephalomyelitis in a rat animal
      model, were found in this study to possess the following immunomodulatory
      properties: (i) they suppressed the proliferation of a CD4 T-cell line raised
      from a multiple sclerosis patient, (ii) they scored the best in vitro TH2/TH1
      cytokine ratio in peripheral blood mononuclear cell cultures derived from 13
      multiple sclerosis patients, inducing IL-10 selectively, and (iii) they bound to
      HLA-DR4, first to be reported for cyclic MBP peptides. In addition, cyclic
      peptides were found to be more stable to lysosomal enzymes and Cathepsin B, D,
      and H, compared to their linear counterparts. Taken together, these data render
      cyclic mimics as putative drugs for treating multiple sclerosis and potentially
      other Th1-mediated autoimmune diseases.

PMID- 15743190
TI  - CHMIS-C: a comprehensive herbal medicine information system for cancer.
AB  - A comprehensive herbal medicine information system for cancer (CHMIS-C) has been
      developed. The current version of the database integrates information on more
      than 200 anticancer herbal recipes that have been used for the treatment of
      different types of cancer in clinic, 900 individual ingredients, and 8500 small
      organic molecules isolated from herbal medicines. Furthermore, subsidiary
      databases of literature references and molecular targets have been constructed. A
      number of web-based searching tools have been developed and integrated into the
      information system for efficient data mining. The compounds in the database have
      been linked to the corresponding entries in the National Cancer Institute's
      database, and to a database of drugs approved by the U.S. Food and Drug
      Administration. This paper provides a description of the individual subsidiary
      databases, integration of the entire database, and data mining tools. We
      demonstrate that this comprehensive information system may be used as an
      effective informatics tool for anticancer drug discovery.

PMID- 15743191
TI  - A shape-based 3-D scaffold hopping method and its application to a bacterial
      protein-protein interaction.
AB  - In this paper, we describe the first prospective application of the shape
      comparison program ROCS (Rapid Overlay of Chemical Structures) to find new
      scaffolds for small molecule inhibitors of the ZipA-FtsZ protein-protein
      interaction, a proposed antibacterial target. The shape comparisons are made
      relative to the crystallographically determined, bioactive conformation of a high
      throughput screening (HTS) hit. The use of ROCS led to the identification of a
      set of novel, weakly binding inhibitors with scaffolds presenting synthetic
      opportunities to further optimize biological affinity and lacking development
      issues associated with the HTS lead. These ROCS-identified scaffolds would have
      been missed using other structural similarity approaches such as ISIS 2D
      fingerprints. X-ray crystallographic analysis of one of the new inhibitors bound
      to ZipA reveals that the shape comparison approach very accurately predicted the
      binding mode. These experimental results validate this use of ROCS for chemotype
      switching or "lead hopping" and suggest that it is of general interest for lead
      identification in drug discovery endeavors.

PMID- 15743192
TI  - Dynamic receptor-based pharmacophore model development and its application in
      designing novel HIV-1 integrase inhibitors.
AB  - We present here a dynamic receptor-based pharmacophore model representing the
      complementary features of the active site region of HIV-1 integrase (IN), which
      was developed from a series of representative conformations of IN. Conformations
      of IN were sampled through a molecular dynamics study of the catalytic domain of
      an IN monomer, and an ensemble of representative IN structures were collected via
      a probability-based representative conformer sampling method that considers both
      the potential energy and the structural similarity of the protein conformations.
      The dynamic pharmacophore model was validated by a set of 128 known inhibitors,
      and the results showed that over 72% of the active inhibitors (IC(50) lower than
      20 microM) could be successfully identified by the dynamic model. Therefore, we
      screened our in-house database of commercially available compounds against this
      model and successfully identified a set of structurally novel IN inhibitors.
      Compounds 7 and 18 with IC(50)s of 8 microM and 15 microM, respectively, against
      the strand transfer reaction were the most potent. Moreover, 7, 8 and 20 showed a
      5-fold selectivity for the strand transfer reaction over 3'-processing.

PMID- 15743193
TI  - NMR studies reveal structural differences between the gallium and yttrium
      complexes of DOTA-D-Phe1-Tyr3-octreotide.
AB  - The somatostatin analogue DOTATOC, DOTA-[Tyr(3)]octreotide, is used for in vivo
      diagnosis and targeted therapy of somatostatin-receptor-positive tumors. DOTATOC
      consists of a disulfide-bridged octapeptide, d-Phe(1)-Cys(2)-Tyr(3)-d-Trp(4)
      Lys(5)-Thr(6)-Cys(7)-Thr(8)-ol, connected to the metal chelator DOTA (1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid). Two metal complexes, Ga(III)-
      and Y(III)-DOTATOC, were reported to differ significantly in somatostatin
      receptor affinity and tumor uptake. Our (1)H and (13)C solution NMR data and
      modeling studies of both compounds are in agreement with a fast conformational
      equilibrium of the peptide part, as previously reported for octreotide itself.
      However, the different coordination geometry of Ga(3+) and Y(3+) (6-fold and 8
      fold, respectively, as known from model compounds) causes pronounced differences
      for the d-Phe(1) residue. For Y(III)-DOTATOC this leads to two conformers
      exchanging slowly on the NMR time scale. From various NMR measurements, they
      could be identified as cis-trans isomers at the amide bond between DOTA chelator
      and first residue (d-Phe(1)H(N)) of the peptide.

PMID- 15743194
TI  - Novel ligands for the chemokine receptor-3 (CCR3): a receptor-modeling study
      based on 5D-QSAR.
AB  - We recently reported the development of a receptor-modeling concept based on 5D
      QSAR (quantitative structure-activity relationships) and which explicitly allows
      for the simulation of induced fit. In this account, we report its utilization
      toward the design of novel compounds able to inhibit the chemokine receptor-3
      (CCR3). The study was based on a total of 141 compounds, representing four
      different substance classes. Using the Quasar software, we built two receptor
      surrogates that yielded a cross-validated r(2) value of 0.950/0.861 and a
      predictive r(2) of 0.879/0.798, respectively. The model was then employed to
      predict the activity of 58 hypothetical compounds featuring two variation
      patterns: lipophilic substitutions and amphiphilic H-bond acceptors. Eleven of
      the proposed ligands show a calculated binding affinity lower than any compound
      within the training set; the most potent candidate molecule is expected to bind
      at an IC(50) of 0.3 nM.

PMID- 15743195
TI  - Design and biological evaluation of linear and cyclic phosphopeptide ligands of
      the N-terminal SH2 domain of protein tyrosine phosphatase SHP-1.
AB  - In an effort to gain further insight into the conformational and topographical
      requirements for recognition by the N-terminal SH2 domain of protein tyrosine
      phosphatase SHP-1, we synthesized a series of linear and cyclic peptides derived
      from the sequence surrounding phosphotyrosine 2267 in the receptor tyrosine
      kinase Ros (EGLNpYMVL). A molecular modeling approach was used to suggest peptide
      modifications sterically compatible with the N-SH2-peptide binding groove and
      possibly enhanced binding affinities compared to the parent peptide. The
      potencies of the synthesized compounds were evaluated by assaying their ability
      to stimulate phosphatase activity as well as by their binding affinities to the
      GST-fused N-SH2 domain of SHP-1. In the series of linear peptides, structural
      modifications of Ros pY2267 in positions pY + 1 to pY + 3 by amino acid residues
      structurally related to Phe, for example l-erythro/threo-Abu(betaPh) (5a, 5b),
      yielded ligands with increased binding affinity. The incorporation of d-amino
      acid residues at pY + 1 and pY + 3 led to inactive peptides. The replacement of
      Phe in both pY + 1 and pY + 3 by Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic
      acid) was also not tolerated due to steric hindrance. Cyclic peptides (13, 14)
      that were linked via residues in positions pY - 1 (Lys) and pY + 2 (Asp/Glu) and
      contained a Gly residue in the bridging unit displayed much lower potencies for
      the stimulation of SHP-1 activity but increased binding affinities compared to
      Ros pY2267. They partially competed with Ros pY2267 in the activation assay. Such
      cyclic structures may serve as scaffolds for competitive SHP-1 inhibitor design
      targeting N-SH2 domain-protein interactions that block SHP-1 activation.

PMID- 15743196
TI  - Rational design, synthesis, and structure-activity relationships of aryltriazoles
      as novel corticotropin-releasing factor-1 receptor antagonists.
AB  - Following the discovery of the very high binding affinity of 4-anilinopyrimidines
      against corticotropin-releasing factor receptor-1 (CRF(1)) (e.g., 1, K(i) = 2
      nM), a new series of triazoles bearing different groups has been synthesized and
      evaluated. The compounds were prepared by cyclizations of N-acyl-S
      methylisothioureas with alkylhydrazines or by cyclizations with hydrazine
      followed by alkylation. While members of this series showed potent binding
      affinity against CRF(1) receptor, there were important differences between the
      different regio- (7 and 12) and stereoisomeric aryltriazoles where the R(1) or
      R(2) side chain in 7 has an asymmetric center. In terms of overall potency,
      aryltriazole analogues such as 7r bearing an N-(alpha-branched benzyl)-N
      propylamino side chain were the most potent, followed by analogues such as 7a,
      with an N-bis(cyclopropyl)methyl-N-propylamino side chain, and analogues such as
      7m, with an N-(alpha-branched aliphatic)-N-propylamino side chain. While the N
      propyl group was crucial for high potency, we hypothesized that the terminal
      methyl mimicked the 5-methyl of pyrazolo[1,5-a]pyrimidines 3 and 4. Correlation
      of the low-energy conformers of compounds of type 3 and 7 generated by
      computational analyses was very good. The size and shape of the N-alkyl group
      dramatically changed the potency of the triazoles, which is in contrast to the
      SAR seen for bicyclic CRF(1) antagonists. In general, the S-enantiomer was much
      more potent than the corresponding R-isomer. Furthermore, to a limited extent in
      the aryltriazole series the substituent on the 5-phenyl ring changed the potency
      up to 9-fold. (S)-1-Methyl-3-[N-(4-fluorophenylpentyl)-N-propyl]amino-5-(2
      methoxy-4-dichlorophenyl)-1H-[1,2,4]triazole [(S)-7r] showed very potent binding
      affinity (K(i) = 2.7 nM) to CRF(1) receptors with an IC(50) of 49 nM in a cAMP
      inhibition assay.

PMID- 15743197
TI  - Synthesis, biological evaluation, and molecular modeling of ribose-modified
      adenosine analogues as adenosine receptor agonists.
AB  - A number of 3'-C-methyl analogues of selective adenosine receptor agonists such
      as CPA, CHA, CCPA, 2'-Me-CCPA, NECA, and IB-MECA was synthesized to further
      investigate the subdomain of the receptor that binds the ribose moiety of the
      ligands. Affinity data at A(1), A(2A), and A(3) receptors in bovine brain
      membranes showed that the 3'-C-modification in adenosine resulted in a decrease
      of the affinity at all three receptor subtypes. When this modification was
      combined with N(6)-substitution with groups that induce high potency and
      selectivity at A(1) receptor, the affinity and selectivity were increased.
      However, all 3'-C-methyl derivatives proved to be very less active than the
      corresponding 2'-C-methyl analogues. The most active compound was found to be 3'
      Me-CPA which displayed a K(i) value of 0.35 microM at A(1) receptor and a
      selectivity for A(1) vs A(2A) and A(3) receptors higher than 28-fold. 2'-Me-CCPA
      was confirmed to be the most selective, high affinity agonist so far known also
      at human A(1) receptor with a K(i) value of 3.3 nM and 2903- and 341-fold
      selective vs human A(2A) and A(3) receptors, respectively. In functional assay,
      3'-Me-CPA, 3'-Me-CCPA, and 2-Cl-3'-Me-IB-MECA inhibited forskolin-stimulated
      adenylyl cyclase activity with IC(50) values ranging from 0.3 to 4.9 microM,
      acting as full agonists. A rhodopsin-based model of the bovine A(1)AR was built
      to rationalize the higher affinity and selectivity of 2'-C-methyl derivatives of
      N(6)-substituted-adenosine compared to that of 3'-C-methyl analogues. In the
      docking exploration, it was found that 2'-Me-CCPA was able to form a number of
      interactions with several polar residues in the transmembrane helices TM-3, TM-6,
      and TM-7 of bA(1)AR which were not preserved in the molecular dynamics simulation
      of 3'-Me-CCPA/bA(1)AR complex.

PMID- 15743198
TI  - Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and
      structurally modified derivatives: potent and selective inhibitors of aldosterone
      synthase.
AB  - Elevated aldosterone levels are key effectors for the development and progression
      of congestive heart failure and myocardial fibrosis. Recently, we proposed
      inhibition of aldosterone synthase (CYP11B2) as an innovative strategy for the
      treatment of these diseases. In this study, the synthesis and biological
      evaluation of E- and Z-(pyridylmethylene)tetrahydronaphthalenes and -indanes
      (1a,b-38a) is described. The activity of the compounds was determined using human
      CYP11B2, and the selectivity was evaluated toward the human steroidogenic enzymes
      CYP11B1, CYP19, and CYP17. The biological results revealed a few rather selective
      inhibitors of CYP11B1, some compounds inhibiting both CYP11B1 and CYP11B2, and a
      large number of highly selective inhibitors of CYP11B2. The most active inhibitor
      was the 3-pyridyl compound 5a (IC(50) = 7 nM). The pyrimidyl-substituted
      derivative 28a was found to be the most selective CYP11B2 inhibitor (IC(50) = 27
      nM) in this series, showing a 120-fold selectivity for CYP11B1 (IC(50) = 3179
      nM). Molecular modeling, i.e., examination of the electronic and steric features
      of selected compounds and homology modeling and docking, was used to understand
      the structure-activity/-selectivity relationships.

PMID- 15743199
TI  - Bisaryloxime ethers as potent inhibitors of transthyretin amyloid fibril
      formation.
AB  - Amyloid fibril formation by the plasma protein transthyretin (TTR), requiring
      rate-limiting tetramer dissociation and monomer misfolding, is implicated in
      several human diseases. Amyloidogenesis can be inhibited through native state
      stabilization, mediated by small molecule binding to TTR's primarily unoccupied
      thyroid hormone binding sites. New native state stabilizers have been discovered
      herein by the facile condensation of arylaldehydes with aryloxyamines affording a
      bisarylaldoxime ether library. Of the library's 95 compounds, 31 were active
      inhibitors of TTR amyloid formation in vitro. The bisaryloxime ethers selectively
      stabilize the native tetrameric state of TTR over the dissociative transition
      state under amyloidogenic conditions, leading to an increase in the dissociation
      activation barrier. Several bisaryloxime ethers bind selectively to TTR in human
      blood plasma over the plethora of other plasma proteins, a necessary attribute
      for efficacy in vivo. While bisarylaldoxime ethers are susceptible to degradation
      by N-O bond cleavage, this process is slowed by their binding to TTR.
      Furthermore, the degradation rate of many of the bisarylaldoxime ethers is slow
      relative to the half-life of plasma TTR. The bisaryloxime ether library provides
      valuable structure-activity relationship insight for the development of
      structurally analogous inhibitors with superior stability profiles, should that
      prove necessary.

PMID- 15743200
TI  - Synthesis, characterization, and comparative in vitro cytotoxicity studies of
      platinum(II), palladium(II), and gold(III) methylsarcosinedithiocarbamate
      complexes.
AB  - This work reports on the synthesis, characterization, and in vitro cytotoxic
      activity of some new platinum(II), palladium(II), and gold(III) derivatives of
      methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as
      potential antitumor agents. The biological activity of these compounds, as
      determined by growth inhibition and apoptosis induction, has been investigated in
      both human leukemic promyelocites HL60 and human squamous cervical adenocarcinoma
      HeLa cell lines, and their activity has been compared to the well-known platinum
      based anticancer agent cisplatin. On the basis of these experimental results,
      [Pd(MSDT)X]n (MSDT = methylsarcosinedithiocarbamate; X = Cl, Br) complexes show a
      strong dose-dependent growth inhibition of both HL60 and HeLa cells, with IC(50)
      values slightly higher than those recorded for cisplatin; moreover,
      [Au(MSDT)X(2)] activity appears significantly higher or, at least, comparable to
      that of the reference drug. Exposure of both cell lines to [Pd(MSDT)X]n and
      [Au(MSDT)X(2)] complexes induces apoptosis, as determined by an Apo2.7 assay.

PMID- 15743201
TI  - Structure-based design, synthesis, and study of potent inhibitors of beta
      ketoacyl-acyl carrier protein synthase III as potential antimicrobial agents.
AB  - Fatty acid biosynthesis is essential for bacterial survival. Components of this
      biosynthetic pathway have been identified as attractive targets for the
      development of new antibacterial agents. FabH, beta-ketoacyl-ACP synthase III, is
      a particularly attractive target, since it is central to the initiation of fatty
      acid biosynthesis and is highly conserved among Gram-positive and -negative
      bacteria. Small molecules that inhibit FabH enzymatic activity have the potential
      to be candidates within a novel class of selective, nontoxic, broad-spectrum
      antibacterials. Using crystallographic structural information on these highly
      conserved active sites and structure based drug design principles, a
      benzoylaminobenzoic acid series of compounds was developed as potent inhibitors
      of FabH. This inhibitor class demonstrates strong antibacterial activity against
      Gram-positive and selected Gram-negative organisms.

PMID- 15743203
TI  - 3D-QSAR comparative molecular field analysis on opioid receptor antagonists:
      pooling data from different studies.
AB  - Three-dimensional quantitative structure-activity relationship (3D-QSAR) models
      were constructed using comparative molecular field analysis (CoMFA) on a series
      of opioid receptor antagonists. To obtain statistically significant and robust
      CoMFA models, a sizable data set of naltrindole and naltrexone analogues was
      assembled by pooling biological and structural data from independent studies. A
      process of "leave one data set out", similar to the traditional "leave one out"
      cross-validation procedure employed in partial least squares (PLS) analysis, was
      utilized to study the feasibility of pooling data in the present case. These
      studies indicate that our approach yields statistically significant and highly
      predictive CoMFA models from the pooled data set of delta, mu, and kappa opioid
      receptor antagonists. All models showed excellent internal predictability and
      self-consistency: q(2) = 0.69/r(2) = 0.91 (delta), q(2) = 0.67/r(2) = 0.92 (mu),
      and q(2) = 0.60/r(2) = 0.96 (kappa). The CoMFA models were further validated
      using two separate test sets: one test set was selected randomly from the pooled
      data set, while the other test set was retrieved from other published sources.
      The overall excellent agreement between CoMFA-predicted and experimental binding
      affinities for a structurally diverse array of ligands across all three opioid
      receptor subtypes gives testimony to the superb predictive power of these models.
      CoMFA field analysis demonstrated that the variations in binding affinity of
      opioid antagonists are dominated by steric rather than electrostatic interactions
      with the three opioid receptor binding sites. The CoMFA steric-electrostatic
      contour maps corresponding to the delta, mu, and kappa opioid receptor subtypes
      reflected the characteristic similarities and differences in the familiar
      "message-address" concept of opioid receptor ligands. Structural modifications to
      increase selectivity for the delta over mu and kappa opioid receptors have been
      predicted on the basis of the CoMFA contour maps. The structure-activity
      relationships (SARs) together with the CoMFA models should find utility for the
      rational design of subtype-selective opioid receptor antagonists.

PMID- 15743202
TI  - Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2
      kinase inhibitors.
AB  - A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as
      inhibitors of VEGFR2 kinase. Herein we describe the structure-activity
      relationship (SAR) of this novel template. Optimization of both aryl rings led to
      very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had
      excellent solubility and good oral PK when dosed as the bis-mesylate salt and
      demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts.
      X-ray crystallography confirmed the proposed binding mode, and comparison of
      oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl
      and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl
      ring.

PMID- 15743204
TI  - Force field design and molecular dynamics simulations of the carbapenem- and
      cephamycin-resistant dinuclear zinc metallo-beta-lactamase from Bacteroides
      fragilis and its complex with a biphenyl tetrazole inhibitor.
AB  - On the basis of molecular dynamics simulations, we investigate the dynamic
      properties of the carbapenem- and cephamycin-resistant dinuclear zinc metallo
      beta-lactamase from Bacteroides fragilis and its complex with a biphenyl
      tetrazole inhibitor, 2-butyl-6-hydroxy-3-[2'-(1H-tetrazol-5-yl)biphenyl-4
      ylmethyl]-3H-quinazolin-4-one 1 (L-159061). The results obtained with the newly
      developed force field parameters for the coordination environment of the
      catalytic zinc ions show that the active site gorge comprising major and minor
      loops gets deeper and narrower upon binding of the inhibitor, which supports the
      previous experimental implication that the structural flexibility of the loop
      structures plays a significant role in enzymatic action. In the presence of the
      inhibitor, the Trp32 side chain at the apex of the major loop covers the entrance
      of active site channel, thereby contributing to the stabilization of the enzyme
      inhibitor complex. In addition to a direct coordination of the inhibitor
      tetrazole ring to the second zinc ion in the active site, the hydrogen bonding of
      Lys167 to the inhibitor carbonyl group and hydrophobic interactions between the
      inhibitor and side chains of loop residues prove to be significant binding forces
      of the enzyme-inhibitor complex.

PMID- 15743205
TI  - A general method for exploiting QSAR models in lead optimization.
AB  - Computer-aided drug design tools can generate many useful and powerful models
      that explain structure-activity relationship (SAR) observations in a quantitative
      manner. These models can use many different descriptors, functional forms, and
      methods from simple linear equations through to multilayer neural nets. Using a
      model, a medicinal chemist can compute an activity, given a structure, but it is
      much harder to work out what changes are needed to make a structure more active.
      The impact of a model on the design process would be greatly enhanced if the
      model were more interpretable to the bench chemist. This paper describes a new
      protocol for performing automated iterative quantitative structure-activity
      relationship (QSAR) studies and presents the results of experiments on two QSAR
      sets from the literature. The fundamental goal of this work is to try to assist
      the chemist in his search for what to make next.

PMID- 15743206
TI  - Discovery of a novel class of reversible non-peptide caspase inhibitors via a
      structure-based approach.
AB  - In this paper, we report a simple structure-based iterative optimizations
      (SUBITO) strategy to identify and optimize new protein ligands and inhibitors.
      The approach is based on a combination of NMR-based screening and computational
      docking methods and enabled the identification of novel chemical leads among
      hundreds of thousands of commercially available compounds by screening only a few
      hundred compounds from a scaffold library followed by iterative screening steps
      where only few dozen compounds are tested. As an application, we report on the
      discovery of a novel class of non-peptide reversible caspase inhibitors, with
      IC(50) values in the low micromolar range.

PMID- 15743207
TI  - Searching for a reliable orientation of ligands in their binding site: comparison
      between a structure-based (Glide) and a ligand-based (FIGO) approach in the case
      study of PDE4 inhibitors.
AB  - Two 3D QSAR Grid/Golpe models, differing in the alignment criterion of the
      studied phosphodiesterase 4 (PDE4) inhibitors, were compared. The docking-guided
      alignment, obtained by exploiting the known 3D structure of the PDE4, was used to
      test and validate the field-fit alignment solution proposed by FIGO procedure.
      The analysis of the direct (docking) and indirect (FIGO) superposition
      methodologies occurs through the comparison of the respective PLS coefficient
      maps. The inclusion in the FIGO algorithm of factors related to the
      hydrophobicity and shape of the molecules leads to promising results, making the
      new FIGO algorithm a valid alternative in the molecule overlay, particularly when
      the 3D structure of the target is unknown.

PMID- 15743208
TI  - Structure of a synthetic fragment of the LALF protein when bound to
      lipopolysaccharide.
AB  - Peptidic lipopolysaccharide (LPS) antagonists are the subject of intensive
      research. We report an NMR and modeling study of LALF-14 (GCKPTFRRLKWKYKCG), a
      synthetic cyclized fragment of the limulus anti-LPS factor (LALF) comprising
      residues 36-47. In a mixture with LPS we observed the transferred NOE effect and
      derived the LPS-bound structure of LALF-14. Neither the free nor the LPS-bound
      peptide displays NOEs indicative of a beta-sheet-like structure that is adopted
      by the fragment in the full-size protein. However, docking calculations show that
      the former structure is not a prerequisite for binding of LALF-14 to LPS.

PMID- 15743209
TI  - Copper(II) and cobalt(III) pyridoxal thiosemicarbazone complexes with
      nitroprusside as counterion: syntheses, electronic properties, and antileukemic
      activity.
AB  - In this paper the syntheses of new pyridoxal thiosemicarbazone copper(II) and
      cobalt(III) complexes with nitroprusside as a counterion and tests on the
      antileukemic activity of three of these complexes toward human cell lines U937
      and CEM are reported. Nitroprusside was chosen in order to test if its ability to
      release NO can increase the biological activity already shown by these complexes.
      The compounds were characterized by spectroscopic and magnetic methods and by
      single-crystal X-ray diffraction.

PMID- 15743211
TI  - Identification of small molecule chemical inhibitors of the collagen-specific
      chaperone Hsp47.
AB  - Hsp47 is a collagen-specific molecular chaperone whose activity has been
      implicated in the pathogenesis of fibrotic diseases. Here, we describe the
      development of an assay for screening libraries of chemical compounds for
      inhibitors of Hsp47. A preliminary screen of 2080 compounds identified four that
      demonstrated inhibitory activity against Hsp47 in vitro, with IC(50) values
      ranging from 3 to 27 muM. Compounds identified through this method may provide
      the basis for development of novel antifibrotic therapeutics.

PMID- 15743210
TI  - Major effect of pyrrolic N-benzylation in norbinaltorphimine, the selective kappa
      opioid receptor antagonist.
AB  - Indolic N-benzylation of naltrindole reportedly extends the duration of delta
      opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid
      receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low
      potency mu-opioid receptor (MOR) partial agonist, was found to affect
      predominantly their MOR activity. When administered systemically in mouse
      antinociceptive assays, N-benzyl-norBNI (1b) had only MOR agonist activity of
      relatively short duration whereas on central administration it had only a KOR
      antagonist action of extremely long duration.

PMID- 15743212
TI  - Photoelectron spectroscopy of chromium-doped silicon cluster anions.
AB  - The photoelectron spectra of chromium-doped silicon cluster anions, CrSi-(n),
      were measured over the size range, n=8-12. Their vertical detachment energies
      were measured to be 2.71, 2.88, 2.87, 2.95, and 3.18 eV, respectively. Our
      results support theoretical calculations by Khanna, Rao, and Jena [Phys. Rev.
      Lett. 89, 016803 (2002)] which found CrSi12 to be an enhanced stability (magic)
      cluster with its chromium atom encapsulated inside a silicon cage and with its
      magnetic moment completely quenched by the effects of the surrounding cage.

PMID- 15743213
TI  - Time resolved resonance Raman observation of the extreme protonation forms of a
      radical zwitterion in water.
AB  - The reactions of the aqueous proton with the zwitterionic p-aminophenoxyl radical
      in strongly basic to extremely acidic aqueous solutions have been investigated
      using time-resolved resonance Raman spectroscopy. The dynamic stability of the
      different protonation forms of the radical, observed on the microsecond time
      scale in this work, has been achieved by controlling the proton exchange rate in
      water. In strongly acidic solutions we observe a rare ring-H+ bonded dication
      species, a key intermediate in the amine hydrolysis. The neutral p-aminophenoxyl
      radical undergoes NH2-deprotonation in strongly basic aqueous solutions, which
      has no analogues in closed-shell amines.

PMID- 15743214
TI  - Laser excitation of NaNe collision pairs probing the A2Pi potential.
AB  - Experimental differential cross sections for the collision process
      Na(3s)2S+Ne+hnu-->Na(3p)2P+Ne are reported. By comparison with calculated cross
      sections, we are able to discriminate between different spectroscopic and quantum
      chemical A2Pi potentials with cm(-1) sensitivity.

PMID- 15743215
TI  - Dynamical and statistical effects of the intrinsic curvature of internal space of
      molecules.
AB  - The Hamilton dynamics of a molecule in a translationally and/or rotationally
      symmetric field is kept rigorously constrained in its phase space. The relevant
      dynamical laws should therefore be extracted from these constrained motions. An
      internal space that is induced by a projection of such a limited phase space onto
      configuration space is an intrinsically curved space even for a system of zero
      total angular momentum. In this paper we discuss the general effects of this
      curvedness on dynamics and structures of molecules in such a manner that is
      invariant with respect to the selection of coordinates. It is shown that the
      regular coordinate originally defined by Riemann is particularly useful to expose
      the curvature correction to the dynamics and statistical properties of molecules.
      These effects are significant both qualitatively and quantitatively and are
      studied in two aspects. One is the direct effect on dynamics: A trajectory
      receives a Lorentz-like force from the curved space as though it was placed in a
      magnetic field. The well-known problem of the trapping phenomenon at the
      transition state is analyzed from this point of view. By showing that the
      trapping force is explicitly described in terms of the curvature of the internal
      space, we clarify that the physical origin of the trapped motion is indeed
      originated from the curvature of the internal space and hence is not dependent of
      the selection of coordinate system. The other aspect is the effect of phase space
      volume arising from the curvedness: We formulate a general expression of the
      curvature correction of the classical density of states and extract its physical
      significance in the molecular geometry along with reaction rate in terms of the
      scalar curvature and volume loss (gain) due to the curvature. The transition
      state theory is reformulated from this point of view and it is applied to the
      structural transition of linear chain molecules in the so-called dihedral angle
      model. It is shown that the curvature effect becomes large roughly linearly with
      the size of molecule.

PMID- 15743216
TI  - Energy decompositions according to physical space partitioning schemes.
AB  - This work describes simple decompositions of the energy of molecular systems
      according to schemes that partition the three-dimensional space. The components
      of those decompositions depend on one and two atomic domains thus providing a
      meaningful chemical information about the nature of different bondings among the
      atoms which compose the system. Our algorithms can be applied at any level of
      theory (correlated or uncorrelated wave functions). The results reported here,
      obtained at the Hartree-Fock level in selected molecules, show a good agreement
      with the chemical picture of molecules and require a low computational cost in
      comparison with other previously reported decompositions.

PMID- 15743217
TI  - Adaptive importance sampling Monte Carlo simulation of rare transition events.
AB  - We develop a general theoretical framework for the recently proposed importance
      sampling method for enhancing the efficiency of rare-event simulations [W. Cai,
      M. H. Kalos, M. de Koning, and V. V. Bulatov, Phys. Rev. E 66, 046703 (2002)],
      and discuss practical aspects of its application. We define the success/fail
      ensemble of all possible successful and failed transition paths of any duration
      and demonstrate that in this formulation the rare-event problem can be
      interpreted as a "hit-or-miss" Monte Carlo quadrature calculation of a path
      integral. The fact that the integrand contributes significantly only for a very
      tiny fraction of all possible paths then naturally leads to a "standard"
      importance sampling approach to Monte Carlo (MC) quadrature and the existence of
      an optimal importance function. In addition to showing that the approach is
      general and expected to be applicable beyond the realm of Markovian path
      simulations, for which the method was originally proposed, the formulation
      reveals a conceptual analogy with the variational MC (VMC) method. The search for
      the optimal importance function in the former is analogous to finding the ground
      state wave function in the latter. In two model problems we discuss practical
      aspects of finding a suitable approximation for the optimal importance function.
      For this purpose we follow the strategy that is typically adopted in VMC
      calculations: the selection of a trial functional form for the optimal importance
      function, followed by the optimization of its adjustable parameters. The latter
      is accomplished by means of an adaptive optimization procedure based on a
      combination of steepest-descent and genetic algorithms.

PMID- 15743218
TI  - Compact and efficient basis sets of s- and p-block elements for model core
      potential method.
AB  - We propose compact and efficient valence-function sets for s- and p-block
      elements from Li to Rn to appropriately describe valence correlation in model
      core potential (MCP) calculations. The basis sets are generated by a combination
      of split MCP valence orbitals and correlating contracted Gaussian-type functions
      in a segmented form. We provide three types of basis sets. They are referred to
      as MCP-dzp, MCP-tzp, and MCP-qzp, since they have the quality comparable with all
      electron correlation consistent basis sets, cc-pVDZ, cc-pVTZ, and cc-pVQZ,
      respectively, for lighter atoms. MCP calculations with the present basis sets
      give atomic correlation energies in good agreement with all-electron
      calculations. The present MCP basis sets systematically improve physical
      properties in atomic and molecular systems in a series of MCP-dzp, MCP-tzp, and
      MCP-qzp. Ionization potentials and electron affinities of halogen atoms as well
      as molecular spectroscopic constants calculated by the best MCP set are in good
      agreement with experimental values.

PMID- 15743219
TI  - Calculation of Verdet constants with time-dependent density functional theory:
      implementation and results for small molecules.
AB  - We report the implementation of a method by which to calculate Verdet constants
      for molecules. The method is based on gauge-including atomic orbitals (GIAOs) and
      density functional theory. Calculations based on this method afford magneto
      optical rotations of the right magnitude for the molecules H2, N2, CO, HF, CH4,
      C2H2, H2O, and CS2. The results are in satisfactory agreement with experiment. We
      investigate the dependency of the results on the gauge origin if GIAOs are not
      chosen, the convergence of the results with the size of the basis set for AOs and
      GIAOs, and for H2O and CS2 a comparison of gas-phase and liquid phase values. For
      the small molecules studied here, large polarized basis sets with diffuse
      functions are required to obtain well converged results. The use of an
      asymptotically correct Kohn-Sham potential is advantageous.

PMID- 15743220
TI  - Dissipative quantum phase space dynamics on dynamically adapting grids.
AB  - A moving grid approach to a dynamical study of dissipative systems is described.
      The dynamics are studied in phase space for the Caldeira-Leggett master equation.
      The grid movement is based on the principle of equidistribution and, by using a
      grid smoothing technique, the grid points trace a path that continuously adapts
      to reflect the dynamics of a phase-space distribution function. The technique is
      robust and allows accurate computations to be obtained for long propagation
      times. The effects of dissipation on the dynamics are studied and results are
      presented for systems subject to both periodic and nonperiodic multiminimum
      potential functions.

PMID- 15743221
TI  - Extensive generalization of renormalized coupled-cluster methods.
AB  - The recently developed completely renormalized (CR) coupled-cluster (CC) methods
      with singles, doubles, and noniterative triples or triples and quadruples [CR
      CCSD(T) or CR-CCSD(TQ), respectively], which are based on the method of moments
      of CC equations (MMCC) [K. Kowalski and P. Piecuch, J. Chem. Phys. 113, 18
      (2000)], eliminate the failures of the standard CCSD(T) and CCSD(TQ) methods at
      larger internuclear separations, but they are not rigorously size extensive.
      Although the departure from strict size extensivity of the CR-CCSD(T) and CR
      CCSD(TQ) methods is small, it is important to examine the possibility of
      formulating the improved CR-CC methods, which are as effective in breaking
      chemical bonds as the existing CR-CCSD(T) and CR-CCSD(TQ) approaches, which are
      as easy to use as the CR-CCSD(T) and CR-CCSD(TQ) methods, and which can be made
      rigorously size extensive. This may be particularly useful for the applications
      of CR-CC methods and other MMCC approaches in calculations of potential energy
      surfaces of large many-electron systems and van der Waals molecules, where the
      additive separability of energies in the noninteracting limit is very important.
      In this paper, we propose different types of CR-CC approximations, termed the
      locally renormalized (LR) CCSD(T) and CCSD(TQ) methods, which become rigorously
      size extensive if the orbitals are localized on nointeracting fragments. The LR
      CCSD(T) and LR-CCSD(TQ) methods rely on the form of the energy expression in
      terms of the generalized moments of CC equations, derived in this work, termed
      the numerator-denominator-connected MMCC expansion. The size extensivity and
      excellent performance of the LR-CCSD(T) and LR-CCSD(TQ) methods are illustrated
      numerically by showing the results for the dimers of stretched HF and LiH
      molecules and bond breaking in HF and H2O.

PMID- 15743222
TI  - Fast and accurate Coulomb calculation with Gaussian functions.
AB  - Coulomb interaction is one of the major time-consuming components in a density
      functional theory (DFT) calculation. In the last decade, dramatic progresses have
      been made to improve the efficiency of Coulomb calculation, including continuous
      fast multipole method (CFMM) and J-engine method, all developed first inside Q
      Chem. The most recent development is the advent of Fourier transform Coulomb
      method developed by Fusti-Molnar and Pulay, and an improved version of the method
      has been recently implemented in Q-Chem. It replaces the least efficient part of
      the previous Coulomb methods with an accurate numerical integration scheme that
      scales in O(N2) instead of O(N4) with the basis size. The result is a much
      smaller slope in the linear scaling with respect to the molecular size and we
      will demonstrate through a series of benchmark calculations that it speeds up the
      calculation of Coulomb energy by several folds over the efficient existing code,
      i.e., the combination of CFMM and J-engine, without loss of accuracy.
      Furthermore, we will show that it is complementary to the latter and together the
      three methods offer the best performance for Coulomb part of DFT calculations,
      making the DFT calculations affordable for very large systems involving thousands
      of basis functions.

PMID- 15743223
TI  - The performance of time-dependent density functional theory based on a
      noncollinear exchange-correlation potential in the calculations of excitation
      energies.
AB  - In the present work we have studied the accuracy of excitation energies
      calculated from spin-flip transitions with a formulation of time-dependent
      density functional theory based on a noncollinear exchange-correlation potential
      proposed in a previous study. We compared the doublet-doublet excitation energies
      from spin-flip transitions and ordinary transitions, calculated the multiplets
      splitting of some atoms, the singlet-triplet gaps of some diradicals, the
      energies of excited quartet states with a doublet ground state. In addition, we
      attempted to calculate transition energies with excited states as reference. We
      compared the triplet excitation energies and singlet-triplet separations of the
      excited state from spin-flip and ordinary transitions. As an application, we show
      that using excited quartet state as reference can help us fully resolve excited
      states spin multiplets. In total the obtained excitation energies calculated from
      spin-flip transitions agree quite well with other theoretical results or
      experimental data.

PMID- 15743224
TI  - Continuity in symmetry and in distinguishability of states: the symmetry numbers
      of nonrigid molecules.
AB  - We establish a connection between the concept of distinguishability of quantum
      states and the concept of continuity in geometric symmetry. For this purpose, we
      employ the continuous symmetry measure and the nuclear wave functions of a
      molecule, and evaluate the physical effects of deviation from geometric symmetry.
      We apply this tool in presenting a unified approach to assigning symmetry numbers
      to rigid and nonrigid molecules, and readdress, as a specific example, the
      evaluation of the temperature dependence of the entropy of cyclobutane and
      cyclohexane. We believe we show that the concept of continuity in geometric
      symmetry provides a more natural and practical approach to the inherent link
      between symmetry and entropy, compared with the classical approach.

PMID- 15743225
TI  - Contracted basis sets for density functional calculations: segmented versus
      general contraction.
AB  - The differences between segmented and general contracted basis sets of double and
      triple zeta quality are analyzed for first and second row elements. Based on
      coverage of the exponent space and the performance for molecular properties, it
      is shown that a segmented contraction requires duplication of one primitive
      function compared to a general contraction for double zeta type basis sets. For
      triple zeta basis sets, segmentation necessitates either addition of one
      primitive function and expanding to a quadruple valence space, or addition of two
      primitive functions. For molecular properties depending on the valence orbitals,
      such as atomization energies, equilibrium distances, and vibrational frequencies,
      some of the inner functions describing the core orbitals can be removed without
      significantly affecting the accuracy. Several of the popular basis sets in common
      use correspond to such core-pruned basis sets.

PMID- 15743226
TI  - Virtual state scattering with cold electrons: para-xylene and para
      difluorobenzene.
AB  - The scattering of electrons with kinetic energies down to a few meV by para
      xylene and para-difluorobenzene has been observed experimentally with an electron
      beam energy resolution of 0.95 to 1.5 meV (full width half maximum). At low
      electron energies the collisions can be considered as cold scattering events
      because the de Broglie wavelength of the electron is considerably larger than the
      target dimensions. The scattering cross sections measured rise rapidly at low
      energy due to virtual state scattering. The nature of this scattering process is
      discussed using s- and p-wave phase shifts derived from the experimental data.
      Scattering lengths are derived of, respectively, -9.5+/-0.5 and -8.0+/-0.5 a.u.
      for para-xylene and para-difluorobenzene. The virtual state effect is interpreted
      in terms of nuclear diabatic and partially adiabatic models, involving the
      electronic and vibronic symmetries of the unoccupied orbitals in the target
      species. The concept of direct and indirect virtual state scattering is
      introduced, through which the present species, in common with carbon dioxide and
      benzene, scatter through an indirect virtual state process, whereas other
      species, such as perfluorobenzene, scatter through a direct process.

PMID- 15743227
TI  - Experimental study of the 39K2 2 3Pi(g) state by perturbation facilitated
      infrared-infrared double resonance and two-photon excitation spectroscopy.
AB  - The 39K2 2 3Pi(g) state has been observed by perturbation facilitated infrared
      infrared double resonance and two-photon excitations. The vibrational numbering
      of the 2 3Pi(g) levels was determined by resolved fluorescence into the bound
      levels as well as to the continuum of the a 3Sigma(u)+ state. The rotational
      assignment of the 2 3Pi(g) levels excited by two-photon transitions was
      determined from excitation frequencies and resolved fluorescence into the bound
      levels of the a 3Sigma(u) + and b 3Pi(u) states. Molecular constants obtained
      from these observed levels agree with theoretical constants.

PMID- 15743228
TI  - Study of vibrational energy localization and redistribution in hydrogen peroxide
      H2O2 at low energy.
AB  - Vibrational energy localization and/or redistribution in hydrogen peroxide H2O2
      is studied at about 4000 cm(-1) above the quantum mechanical ground state using
      the ab initio potential energy surface of Koput, Carter, and Handy [J. Phys.
      Chem. A 102, 6325 (1998)]. In this work, the recently derived canonical
      perturbation procedure for floppy molecules serves two purposes. First, from the
      quantum mechanical point of view, it is shown that the energies of the lowest 130
      states are reproduced with an average error smaller than 1.5 cm(-1) by a two
      dimensional Hamiltonian, which is a function of the torsion and OO-stretch
      coordinates and momenta, while the other four degrees of freedom contribute only
      through powers of good quantum numbers. Moreover, the canonical perturbation
      procedure is also used in classical mechanics calculations, in order to define
      meaningful local modes, for which the ingoing and outgoing energy flows are
      monitored. Almost all the individual trajectories launched on the ab initio
      surface display the same behavior, that is, the superposition of (a) rapid (few
      hundreds of femtoseconds) and quasiperiodic energy exchanges between the two OH
      stretches and between the torsion and OO-stretch, and (b) slower (few to several
      picoseconds) but erratic-looking energy flows between all degrees of freedom.
      When averaging over large numbers of trajectories with the same local mode
      energies at time t=0, one observes instead a smooth and irreversible energy flow
      between all degrees of freedom, which usually thermalize in the range of several
      tens of picoseconds, that is, on time scales larger than the 5 ps period
      associated with the quantum density of states.

PMID- 15743229
TI  - Quantum statistical and wave packet studies of insertion reactions of S(1D) with
      H2, HD, and D2.
AB  - A thorough theoretical investigation of the reactions between S(1D) and various
      hydrogen isotopomers (H2, D2, and HD) has been carried out using a recent ab
      initio potential energy surface. State-resolved integral and differential cross
      sections, thermal rate constants, and their dependence on energy or temperature
      were obtained from quantum mechanical capture probabilities within a statistical
      model. For comparison, the J=0 reaction probabilities were also computed using an
      exact wave packet method. The statistical results are in excellent agreement with
      available exact differential and integral cross sections. The comparison with
      experimental results shows that the agreement is reasonably good in general, but
      some significant differences exist, particularly for the SD/SH branching ratio in
      the S(1D)+HD reaction.

PMID- 15743230
TI  - Finite length nanotubes: ground state degeneracy and single-electron spectrum.
AB  - By means of the Rutherford method it is found that in zigzag carbon nanotubes
      with an even number n=2j of hexagons in a tube ring the gap between occupied and
      empty single-electron levels disappears. The frontier level is shown to be at
      least doubly degenerate. The reason for the loss of the zero level (for n=2j)
      upon reaching the infinite length limit is discussed. The existence of a lot of
      states, specific for finite nanotubes, with the energy very close to the Fermi
      level is shown, and the number of these states is estimated. The existence of a
      narrow (of order 10(-4) eV) conduction band, formed by edge states, is
      demonstrated in tight binding approximation. If the Coulomb interaction is taken
      into account, the half-filled degenerate pi-electronic level continues to exist.
      The open shell Hartree-Fock theory demonstrates the degenerate configuration
      splitting onto three equidistant terms: two singlets with the seniority numbers 0
      and 1, and the lowest triplet in accordance with the Hund rule. The behavior of
      the single-electron gap is alike for all three terms: the gap is of the order 0.2
      0.01 eV. The Rutherford method gives analytical results for armchair nanotubes as
      well, which explains the gap oscillations as a function of the tube length with a
      period of three rings. Application of the degenerate open shell Hartree-Fock
      theory supports this explanation.

PMID- 15743231
TI  - The NaK 1(b) 3Pi(Omega=0) state hyperfine structure and the 1(b) 3Pi(Omega=0)
      approximately 2(A) 1Sigma+ spin-orbit interaction.
AB  - We have measured the hyperfine structure of mutually perturbing rovibrational
      levels of the 1(b) 3Pi0 and 2(A) 1Sigma+ states of the NaK molecule, using the
      perturbation-facilitated optical-optical double resonance method with
      copropagating lasers. The unperturbed 1(b) 3Pi0 levels are split into four
      hyperfine components by the Fermi contact interaction bFIS. Mixing between the
      1(b) 3Pi0 and 2(A) 1Sigma+ levels imparts hyperfine structure to the nominally
      singlet component of the perturbed levels and reduces the hyperfine splitting of
      the nominally triplet component. Theoretical analysis relates these observations
      to the hyperfine splitting that each 1(b) 3Pi0 level would have if it were not
      perturbed by a 2(A) 1Sigma+ level. Using this analysis, we demonstrate that
      significant hyperfine splitting arises because the 1(b) 3Pi0 state cannot be
      described as pure Hund's case (a). We determine bF for the 1(b) 3Pi0 levels and
      also a more accurate value for the magnitude of the singlet-triplet spin-orbit
      coupling HSO=[1(b) 3Pi0(vb,J)(H(SO))2(A) 1Sigma+(vA,J). Using the known
      spectroscopic constants of the 1(b) 3Pi state, we obtain bF=0.009 89+/-0.000 27
      cm(-1). The values of (H(SO)) are found to be between 2 and 3 cm(-1), depending
      on vb, vA, and J. Dividing (H(SO)) by calculated vibrational overlap integrals,
      and taking account of the 1(b) 3Pi(Omega) rotational mixing, we can determine the
      magnitude of the electronic part H(el) of H(SO). Our results yield
      (H(el))=(16.33+/-0.15) cm(-1), consistent with our previous determinations using
      different techniques.

PMID- 15743232
TI  - A 3000 K laboratory emission spectrum of water.
AB  - An emission spectrum of hot water with a temperature of about 3000 K is obtained
      using an oxy-acetylene torch. This spectrum contains a very large number of
      transitions. The spectrum, along with previous cooler laboratory emission spectra
      and an absorption spectrum recorded from a sunspot, is analyzed in the 500-2000
      cm(-1) region. Use of a calculated variational linelist for water allows
      significant progress to be made on assigning transitions involving highly excited
      vibrational and rotational states. In particular emission from rotationally
      excited states up to J=42 and vibrational levels with up to eight quanta of
      bending motion are assigned.

PMID- 15743233
TI  - The He-LiH potential energy surface revisited. II. Rovibrational energy transfer
      on a three-dimensional surface.
AB  - We use our rigid rotor He-LiH potential energy surface [B. K. Taylor and R. J.
      Hinde, J. Phys. Chem. 111, 973 (1999)] as a starting point to develop a three
      dimensional potential surface that describes the interaction between He and a
      rotating and vibrating LiH molecule. We use a fully quantum treatment of the
      collision dynamics on the current potential surface to compute rovibrational
      state-to-state cross sections. We compute excitation and relaxation vibrational
      rate constants as a function of temperature by integrating these cross sections
      over a Maxwell-Boltzmann translational energy distribution and summing over
      Boltzmann-weighted initial rotational levels. The rate constants for vibrational
      excitation of LiH are very small for temperatures below 300 K. Rate constants for
      vibrational relaxation of excited LiH molecules, however, are several orders of
      magnitude larger and show very little temperature dependence, suggesting that the
      collisions that result in vibrational relaxation are governed by long-range
      attractive interactions.

PMID- 15743234
TI  - Theoretical mechanistic study on the ion-molecule reaction of SiCN+/SiNC+ with
      H2O.
AB  - The gas-phase ion-molecule reactions play very important roles in interstellar
      and in plasma chemistry. Motivated by recent astrophysical detection of the
      SiCN/SiNC radicals and laboratory characterization of some SiCN-containing
      species, we carried out a detailed potential energy survey on the SiCN+/SiNC(+) +
      H2O reaction at the Becke's three-parameter Lee-Yang-Parr-B3LYP/6-311G(d,p) and
      coupled cluster with single, double, and triple excitations-CCSD(T)/6-311 +
      G(2df,p) (single-point) levels as an attempt towards understanding the
      SiCN+/SiNC+ reaction mechanisms. In contrast to the carbene-featured analogous
      CCN+/CNC(+) + H2X (X=O,S) reactions, the title reaction SiCN+/SiNC(+) + H2O are
      not associated with any competitive silylene-insertion characters. Moreover, the 
      CN <--> -NC interconversion has a low barrier and plays an important role in
      determining the final product distributions. This is also in marked difference
      from the CCN+/CNC+ reaction. It is shown that the isomeric sila-cations SiCN+ and
      SiNC+ can both react with H2O to barrierlessly generate the major product P1
      HOSi(+) + HCN and the minor one P3 HOSi(+) + HNC, whereas other low-lying
      products such as P2 SiNCO(+) + H2, and P(0) H2NSi(+) + CO are kinetically
      unfeasible. The high efficiency of the SiCN+/SiNC+ reaction towards H2O and the
      potential importance of SiCN+/SiNC+ ion chemistry in interstellar and SiCN-based
      microelectric and photoelectric processes strongly appeals for future laboratory
      investigations on the SiCN+/SiNC+ chemical reactivity.

PMID- 15743235
TI  - Photodissociation spectroscopy of trapped protonated tryptophan.
AB  - We have coupled a quadrupole ion trap with a frequency doubled optical parametric
      oscillator laser. The photodissociation spectrum of the protonated tryptophan ion
      from 215 to 320 nm is reported. The yields of fragmentation on each mass channel
      as a function of the laser wavelength were obtained. We also report experiments
      involving multiple stages of laser induced dissociation and discuss possible
      structures for the fragmentation products.

PMID- 15743236
TI  - Rotational distributions following van der Waals molecule dissociation:
      comparison between experiment and theory for benzene-Ar.
AB  - The translational energy release distribution for dissociation of benzene-Ar has
      been measured and, in combination with the 6(1)(0) rotational contour of the
      benzene product observed in emission, used to determine the rotational J,K
      distribution of 0(0) benzene products formed during dissociation from 6(1).
      Significant angular momentum is transferred to benzene on dissociation. The 0(0)
      rotational distribution peaks at J=31 and is skewed to low K:Javerage=27,
      (K)average=10.3. The average angle between the total angular momentum vector and
      the unique rotational axis is determined to be 68 degrees. This indicates that
      benzene is formed tumbling about in-plane axes rather than in a frisbeelike
      motion, consistent with Ar "pushing off" benzene from an off-center position
      above or below the plane. The J distribution is very well reproduced by angular
      momentum model calculations based on an equivalent rotor approach [A. J.
      McCaffery, M. A. Osborne, R. J. Marsh, W. D. Lawrance, and E. R. Waclawik, J.
      Chem. Phys. 121, 1694 (2004)], indicating that angular momentum constraints
      control the partitioning of energy between translation and rotation. Calculations
      for p-difluorobenzene-Ar suggest that the equivalent rotor model can provide a
      reasonable prediction of both J and K distributions in prolate (or near prolate)
      tops when dissociation leads to excitation about the unique, in-plane axis.
      Calculations for s-tetrazine-Ar require a small maximum impact parameter to
      reproduce the comparatively low J values seen for the s-tetrazine product. The
      three sets of calculations show that the maximum impact parameter is not
      necessarily equal to the bond length of the equivalent rotor and must be treated
      as a variable parameter. The success of the equivalent rotor calculations argues
      that angular momentum constraints control the partitioning between rotation and
      translation of the products.

PMID- 15743237
TI  - Electronic spectroscopy of small toluene clusters.
AB  - Small clusters of toluene(n) (n = 1-8) were created in a supersonic expansion of
      toluene with argon as a carrier gas. Mass-selected resonance enhanced multiphoton
      ionization spectra of these clusters were recorded for each n. For the dimer, the
      appearance of the spectrum under warm and very cold conditions was studied. We
      discuss previous results in the light of the present spectra. For n>2, the
      spectra resemble very closely that of the dimer.

PMID- 15743238
TI  - Clusters of glycolic acid with three to six water molecules.
AB  - Semiempirical, ab initio, and density functional theory calculations are used to
      locate many low-energy minima on the potential energy surfaces of the CH2OHCOOH
      (H2O)n complexes with n = 3,4,5,6. In the clusters with three, four, and five
      water molecules, the lowest-energy structure consists of a (H2O)n complex, not
      necessarily of lowest energy, hydrogen bonded to the carboxylic group of the
      glycolic acid. The lowest-energy structure for n = 6 is similar except that the
      water hexamer is hydrogen bonded to both the carboxylic and alpha-hydroxyl groups
      of the acid. In all the lowest-energy clusters, the intramolecular hydrogen bond
      remains intact in the glycolic acid.

PMID- 15743239
TI  - Theoretical study of the photoinduced transfer among the ground state and two
      metastable states in [Fe(CN)5NO]2-.
AB  - Ab initio calculations were performed to investigate photoinduced transfers among
      the ground state (GS) and two metastable states (MS1 and MS2) of [Fe(CN)5NO]2-.
      We obtained the global potential energy surface of the electronic ground state by
      a scheme of multireference singly and doubly excited configuration interaction
      followed by a Davidson-type quadruple correction (MRSDCI+Q). The ground state
      surface has three local minima corresponding to GS, MS1, and MS2. The character
      of bond between Fe and the nitrosyl group are discussed. We carried out
      calculations of the lower five electronic excited states by MRSDCI+Q. The main
      configurations of these lower five excited states were represented by the dFe-
      >pi*NO transition accompanied by considerable back-donation. The potential energy
      surfaces of the six states, including the ground state, were obtained by state
      averaged complete active space self-consistent field calculations. The surfaces
      have several conical intersections and avoided crossings in the reaction pathway.
      The photoinduced transfers among GS, MS1, and MS2 are caused by the nonadiabatic
      effect near these crossings.

PMID- 15743240
TI  - Protonated clathrate cages enclosing neutral water molecules: (H+)(H2O)21 and
      (H+)(H2O)28.
AB  - This paper describes a systematic study on the clathrate structure of (H+)(H2O)21
      using tandem mass spectrometry, vibrational predissociation spectroscopy, Monte
      Carlo simulations, and density functional theory calculations. We produced
      (H+)(H2O)n from a continuous corona-discharged supersonic expansion and observed
      three anomalies simultaneously at the cluster temperature near 150 K, including
      (1) the peak at n=21 is more intense than its neighboring ions in the mass
      spectrum, (2) the size-dependent dissociation fractions show a distinct drop for
      the 21-mer, and (3) the infrared spectrum of (H+)(H2O)21 exhibits only a single
      feature at 3699 cm(-1), corresponding to the free-OH stretching of three
      coordinated water molecules. Interestingly, the anomalies appear or disappear
      together with cluster temperature, indicating close correlation of these three
      observations. The observations, together with Monte Carlo simulations and density
      functional theory calculations, corroborate the notion for the formation of a
      distorted pentagonal dodecahedral (5(12)) cage with a H2O molecule in the cage
      and a H3O+ ion on the surface for this "magic number" water cluster ion. The
      dodecahedral cage melts at higher temperatures, as evidenced by the emergence of
      a free-OH stretching feature at 3717 cm(-1) for the two-coordinated water in
      (H+)(H2O)21 produced in a warmer molecular beam. Extension of this study to
      larger clusters strongly suggests that the experimentally observed isomer of
      (H+)(H2O)28 is most likely to consist of a distorted protonated
      pentakaidecahedral (5(12)6(3)) cage enclosing two neutral water molecules.

PMID- 15743241
TI  - Excited states dynamics of DNA and RNA bases: characterization of a stepwise
      deactivation pathway in the gas phase.
AB  - Radiationless deactivation pathways of excited gas phase nucleobases were
      investigated using mass-selected femtosecond resolved pump-probe resonant
      ionization. By comparison between nucleobases and methylated species, in which
      tautomerism cannot occur, we can access intrinsic mechanisms at a time resolution
      never reported so far (80 fs). At this time resolution, and using appropriate
      substitution, real nuclear motion corresponding to active vibrational modes along
      deactivation coordinates can actually be probed. We provide evidence for the
      existence of a two-step decay mechanism, following a 267 nm excitation of the
      nucleobases. The time resolution achieved together with a careful zero time-delay
      calibration between lasers allow us to show that the first step does correspond
      to intrinsic dynamics rather than to a laser cross correlation. For adenine and 9
      methyladenine a first decay component of about 100 fs has been measured. This
      first step is radically increased to 200 fs when the amino group hydrogen atoms
      of adenine are substituted by methyl groups. Our results could be rationalized
      according to the effect of the highly localized nature of the excitation combined
      to the presence of efficient deactivation pathway along both pyrimidine ring and
      amino group out-of-plane vibrational modes. These nuclear motions play a key role
      in the vibronic coupling between the initially excited pipi* and the dark npi*
      states. This seems to be the common mechanism that opens up the earlier phase of
      the internal conversion pathway which then, in consideration of the rather fast
      relaxation times observed, would probably proceed via conical intersection
      between the npi* relay state and high vibrational levels of the ground state.

PMID- 15743242
TI  - Gallium oxide and dioxide: investigation of the ground and low-lying electronic
      states via anion photoelectron spectroscopy.
AB  - The GaO and GaO2 molecules were investigated using negative ion photoelectron
      spectroscopy. All the photoelectron spectra showed vibrationally resolved
      progressions. With the aid of electronic structure calculations and Franck-Condon
      spectral simulations, different molecular parameters and energetics of GaO-/GaO
      and GaO2-/GaO2 were determined, including the electron affinity of GaO, the
      vibrational frequency of GaO-, and the term energy, spin-orbit splitting, and
      vibrational frequency for the first excited A 2PiOmega state of GaO. The GaO2-
      photoelectron spectra comprised three bands assigned as transitions from the
      linear X 1Sigma(g)+ ground state of GaO2- to three linear neutral states: the A
      2Pi(g), B 2Pi(u), and C 2Sigma(u) + states. The symmetric stretch frequencies of
      the anion and three neutral states as well as the spin-orbit splitting of the
      neutral 2Pi states were determined. Electronic structure calculations found the
      neutral lowest energy linear structure to be only 63 meV higher than the neutral
      bent geometry.

PMID- 15743243
TI  - Nonlinear response of the benzene molecule to strong magnetic fields.
AB  - The fourth-rank hypermagnetizability tensor of the benzene molecule has been
      evaluated at the coupled Hartree-Fock level of accuracy within the conventional
      common-origin approach, adopting gaugeless basis sets of increasing size and
      flexibility. The degree of convergence of theoretical tensor components has been
      estimated allowing for two different coordinate systems. It is shown that a
      strong magnetic field perpendicular to the plane of the molecule causes a
      distortion of the electron charge density, which tends to concentrate in the
      region of the C-C bonds. This charge contraction has a dynamical origin, and can
      be interpreted as a feedback effect in terms of the classical Lorentz force
      acting on the electron current density.

PMID- 15743244
TI  - Inelastic state-to-state scattering of OH (2Pi3/2, J=3/2,f) by HCl.
AB  - Parity resolved state-to-state cross sections for inelastic scattering of OH
      (X2Pi) by HCl were measured in a crossed molecular beam experiment at the
      collision energy of 920 cm(-1). The OH (X2Pi) radicals were prepared in a single
      quantum state, Omega=3/2, J=3/2, MJ=3/2, f, by means of electrostatic state
      selection in a hexapole field. The rotational distribution of the scattered OH
      radicals by HCl was probed by saturated LIF spectroscopy of the 0-0 band of the A
      2Sigma+ - X 2Pi transition. Relative state-to-state cross sections were measured
      for rotational excitations up to J=9/2 within the Omega=3/2 spin-orbit manifold
      and up to J=7/2 within the Omega=1/2 spin-orbit manifold. A propensity for spin
      orbit conserving transitions was found, but no propensity for excitation into a
      particular Lambda-doublet component of the same rotational state was evident. The
      data are presented and discussed in comparison with results previously obtained
      for collisions of OH with CO (Ecoll=450 cm(-1)) and N2 (Ecoll=410 cm(-1)) and
      with new data we have measured for the OH+CO system at a comparable collision
      energy (Ecoll=985 cm(-1)). This comparison suggests that the potential energy
      surface (PES) governing the interaction between OH and HCl is more anisotropic
      than the PES's governing the intermolecular interaction of OH with CO and N2.

PMID- 15743245
TI  - A theoretical study for the reaction of vinyl cyanide C2H3CN(X1A') with the
      ground state carbon atom C(3P) in cold molecular clouds.
AB  - The reaction of the ground state atomic carbon, C(3P), with simple unsaturated
      nitrile, C2H3CN(X1A' (vinyl cyanide), is investigated theoretically to explore
      the probable routes for the formation of carbon-nitrogen-bearing species in
      extraterrestrial environments particularly of ultralow temperature. Five
      collision complexes without entrance barrier as a result of the carbon atom
      addition to the pi systems of C2H3CN are characterized. The B3YLP/6-311G(d,p)
      level of theory is utilized in obtaining the optimized geometries, harmonic
      frequencies, and energies of the intermediates, transition states, and products
      along the isomerization and dissociation pathways of each collision complex.
      Subsequently, with the facilitation of computed RRKM rate constants at collision
      energy of 0-10 kcal/mol, the most probable paths for each collision complexes are
      determined, of which the CCSD(T)/6-311G(d,p) energies are calculated. The major
      products predicted are exclusively due to the hydrogen atom dissociations, while
      the products of H2, CN, and CH2 decompositions are found negligible. Among many
      possible H-elimination products, cyano propargyl (p4) and 3-cyano propargyl (p5)
      are the most probable, in which p5 can be formed via two intermediates, cyano
      allene (i8) and cyano vinylmethylene (i6), while p4 is yielded from i8. The study
      suggests this class of reaction is an important route to the synthesis of
      unsaturated nitriles at the temperature as low as 10 K, and the results are
      valuable for future chemical models of interstellar clouds.

PMID- 15743246
TI  - Four-component Hartree-Fock calculations of magnetic-field induced circular
      birefringence--Faraday effect--in noble gases and dihalogens.
AB  - The effects of relativity on the magnetic-field induced circular birefringence,
      or Faraday effect, in He, Ne, Ar, Xe, Rn, F2, Cl2, Br2, and I2 have been
      determined at the four-component Hartree-Fock level of theory. A measure of the
      birefringence is given by the Verdet constant, which is a third-order molecular
      property and thus relates to quadratic response functions. A fully analytical
      nonlinear polarization propagator approach is employed. The results are gauge
      invariant as a consequence of the spatial symmetries in the molecular systems.
      The calculations include electronic as well as vibrational contributions to the
      property. Comparison with experiment is made for He, Ne, Ar, Xe, and Cl2, and,
      apart from neon, the theoretical values of the Verdet constant are within 10% of
      the experimental ones. The inclusion of nonrelativistically spin-forbidden
      excitations in the propagator parametrization has significant effects on the
      dispersion in general, but such effects are in the general case largely explained
      by the use of a resonant-divergent propagator theory. In the present work we do,
      however, observe noticeable relativistic corrections to the Verdet constant in
      the off-resonant regions for systems with light elements (F2 and Cl2), and
      nonrelativistic results for the Verdet constant of Br2 are in error by 25% in the
      low-frequency region.

PMID- 15743248
TI  - Quasi-unary homogeneous nucleation of H2SO4-H2O.
AB  - We show that the binary homogeneous nucleation (BHN) of H2SO4-H2O can be treated
      as quasi-unary nucleation of H2SO4 in equilibrium with H2O vapor. A scheme to
      calculate the evaporation coefficient of H2SO4 molecules from H2SO4-H2O clusters
      is presented and a kinetic model to simulate the quasi-unary nucleation of H2SO4
      H2O is developed. In the kinetic model, the growth and evaporation of sulfuric
      acid clusters of various sizes are explicitly simulated. The kinetic quasi-unary
      nucleation model does not have two well-recognized problems associated with the
      classical BHN theory (violation of the mass action law and mismatch of the
      cluster distribution for monomers) and is appropriate for the situations where
      the assumption of equilibrium cluster distribution is invalid. The nucleation
      rates predicted with our quasi-unary kinetic model are consistent with recent
      experimental nucleation experiments in all the cases studied, while the most
      recent version of the classical BHN model systematically overpredicts the
      nucleation rates. The hydration of sulfuric acid clusters, which is not
      considered in the classical model but is accounted for implicitly in our kinetic
      quasi-unary model, is likely to be one of physical mechanisms that lead to lower
      nucleation rates. Further investigation is needed to understand exactly what
      cause the difference between the kinetic quasi-unary model and the classical BHN
      model.

PMID- 15743247
TI  - The complete T-->V,R energy conversion in three-body collisions within the hard
      sphere model.
AB  - It is shown that in hard sphere (impulsive) collisions of atoms with diatomic
      molecules, complete conversion of the collision energy into the internal energy
      of the diatomic partner is possible for any number of impacts between the elastic
      balls representing the particles. The corresponding collision geometries and
      relations between the masses of the particles are described in detail.

PMID- 15743249
TI  - Anomalous Kerr effect relaxation in an alternating field.
AB  - Perturbation theory is used to derive the complex harmonic components (stationary
      regime) arising in Kerr effect relaxation for an assembly of nonelectrically
      interacting, polar, and polarizable symmetric-top molecules acted on by a strong
      dc bias electric field superimposed on a weak ac electric field. The approach
      starts from a fractional kinetic equation written in configuration space and
      represents an extension of the Smoluchowski equation to fractional dynamics. This
      equation is solved in the context of a subdiffusive process characterized by an
      anomalous exponent alpha ranging from 0 to 1, the Brownian limit. By using a
      perturbation procedure restricted to the second order in the ac field strength,
      analytic expressions for the electric birefringence spectra representing the
      frequency dependence of the first (in omega) and the second (in 2omega) harmonic
      components are obtained. Various Cole-Cole-like diagrams are presented in order
      to illustrate the results so obtained and to emphasize the role played by the
      fractal parameter alpha in the anomalous diffusion collision process. A
      comparison of our theoretical model with experimental measurements of the ac Kerr
      effect response of a dilute polymer solution [poly(3-hexylthiophene)] appears to
      be quite satisfactory.

PMID- 15743250
TI  - On the thermodynamic stability and structural transition of clathrate hydrates.
AB  - Gas mixtures of methane and ethane form structure II clathrate hydrates despite
      the fact that each of pure methane and pure ethane gases forms the structure I
      hydrate. Optimization of the interaction potential parameters for methane and
      ethane is attempted so as to reproduce the dissociation pressures of each simple
      hydrate containing either methane or ethane alone. An account for the structural
      transitions between type I and type II hydrates upon changing the mole fraction
      of the gas mixture is given on the basis of the van der Waals and Platteeuw
      theory with these optimized potentials. Cage occupancies of the two kinds of
      hydrates are also calculated as functions of the mole fraction at the
      dissociation pressure and at a fixed pressure well above the dissociation
      pressure.

PMID- 15743251
TI  - Polarization response of water and methanol investigated by a polarizable force
      field and density functional theory calculations: implications for charge
      transfer.
AB  - Electronic polarization response in hydrogen-bond clusters and liquid
      configurations of water and methanol has been studied by density functional
      theory (DFT) and by a polarizable force field based on the chemical potential
      equalization (CPE) principle. It has been shown that an accurate CPE
      parametrization based on isolated molecular properties is not completely
      transferable to strongly interacting hydrogen-bond clusters with discrepancies
      between CPE and DFT overall dipole moments as large as 15%. This is due to the
      lack of intermolecular charge transfer in the standard CPE implementation. A CPE
      scheme for evaluating the amount of transferred charge has been developed. The
      charge transfer parameters are determined with the aid of accurate DFT
      calculations using only hydrogen-bond dimer configurations. The amount of
      transferred charge is found to be of the order of few hundredths of electrons, as
      already found in recent studies on hydrogen-bond systems. The parameters of the
      model are then used, without further adjustment, to different hydrogen-bond
      clustered forms of water and methanol (oligomer and liquid configurations). In
      agreement with different approaches proposed in literature for studying charge
      transfer effects, the transferred charge in hydrogen-bond dimers is found to
      decrease exponentially with the hydrogen-bond distance. When allowance is made
      for charge transfer according to the proposed scheme, the CPE dipole moments are
      found to reproduce satisfactorily the DFT data.

PMID- 15743252
TI  - Phase separation of the Widom-Rowlinson mixture in confined geometry.
AB  - The behavior of binary Widom-Rowlinson [J. Chem. Phys. 52, 1670 (1970)] mixture
      in confined geometry is investigated. The influence of confinement on phase
      separation is examined. Coexistence curves for the mixture in slitlike pores and
      pores of complex geometry are calculated in Monte Carlo simulations. Finite size
      scaling analysis is used to determine precisely the location of critical point
      for the bulk mixture.

PMID- 15743253
TI  - A comparison of relaxation processes in structurally related van der Waals glass
      formers: the role of internal degrees of freedom.
AB  - Depolarized dynamic light scattering (DLS), dielectric relaxation (DS), and
      deuterium NMR studies of fragile van der Waals glass forming liquids
      phenylphthalein-dimethylether (PDE) and cresolphthalein-dimethylether (KDE) are
      presented. In PDE a new dielectric loss process was found, which can be
      attributed to the 180 degrees flip of the phenyl rings. The previous finding that
      the distribution of the structural relaxation times measured for PDE and KDE by
      DS is substantially narrower than that measured by DLS is explained by partial
      decoupling of the dynamics of the dipole moment from the structural relaxation of
      the sample. The dynamics of PDE and KDE is compared with the previous studies of
      two other structurally similar liquids: 1,1'-di(4-methoxy-5
      methylphenyl)cyclohexane (BMMPC) and 1,1'-bis(p-methoxyphenyl)cyclohexane (BMPC)
      in order to relate dynamical features with the chemical structure of the
      material. The evidence for the intramolecular character of the secondary
      relaxations observed in BMPC and PDE is presented.

PMID- 15743254
TI  - Isotropic proton-detected local-field nuclear magnetic resonance in solids.
AB  - A nuclear magnetic resonance method is presented which produces linear, isotropic
      proton-detected local-field spectra for INS spin systems in powdered samples. The
      method, heteronuclear isotropic evolution (HETIE), refocuses the anisotropic
      portion of the heteronuclear dipolar coupling frequencies by evolving the system
      under a series of specially designed Hamiltonians and evolution pathways. The
      theory behind HETIE is presented along with experimental studies conducted on a
      powdered sample of ferrocene, demonstrating the methodology outlined in this
      paper. Applications of HETIE for use in structure determination in the solid
      state are discussed.

PMID- 15743255
TI  - The structure of hyperspherical fluids in various dimensions.
AB  - The structure of hard, hyperspherical fluids in dimension one, two, three, four,
      and five has been examined by calculating the pair correlation function using a
      Monte Carlo simulation. The pair correlation functions match known results in
      one, two, and three dimensions. The contact value of the pair correlation
      functions in all the different dimensions agrees well with the theory of Song,
      Mason, and Stratt [J. Phys. Chem. 93, 6916 (1989)]. The decrease in ordering as
      the dimension is increased is readily apparent in the structure of the pair
      correlation function.

PMID- 15743256
TI  - Hydrothermal reactions of formaldehyde and formic acid: free-energy analysis of
      equilibrium.
AB  - The chemical equilibria concerning formaldehyde and formic acid are
      computationally investigated in water over a wide range of thermodynamic
      conditions. The free energy is evaluated in the method of energy representation
      for the solvent effect on the decomposition processes of these two compounds. The
      solvation is found to suppress the production of nonpolar species from a polar.
      In the two competitive decomposition reactions of formic acid, the solvent
      strongly inhibits the decarboxylation (HCOOH-->CO2+H2) and its effect is
      relatively weak for the decarbonylation (HCOOH-->CO+H2O). The equilibrium weights
      for the two decomposition pathways of formic acid are determined by the
      equilibrium constant of the water-gas-shift reaction (CO+H2O-->CO2+H2), which is
      an essential and useful process in fuel technology. The reaction control by the
      solvent is then examined for the water-gas-shift reaction. Through the comparison
      of the equilibrium constants in the absence and presence of solvent, even the
      favorable side of the reaction is shown to be tuned by the solvent density and
      temperature. The reaction equilibrium is further treated for aldehyde
      disproportionation reactions involving formaldehyde and formic acid. The
      disproportionation reactions are found to be subject to relatively weak solvent
      effects and to be dominated by the electronic contribution.

PMID- 15743257
TI  - Topological derivation of shape exponents for stretched exponential relaxation.
AB  - In homogeneous (ideal) glasses, the important dimensionless stretched-exponential
      shape parameter beta is described by magic (not adjusted) simple fractions
      derived from fractal configuration spaces of effective dimension d* determined by
      different topological axioms (rules) in the presence (absence) of a forcing
      electric field. The rules are based on a new central principle for defining
      glassy states: equal a priori distributions of fractal residual configurational
      entropy. Our approach and its beta estimates are fully supported by the results
      of relaxation measurements involving many different glassy materials and probe
      methods. The present unique topological predictions for beta typically agree with
      observed values to approximately 1% and indicate that for field-forced conditions
      beta should be constant for appreciable ranges of such exogenous variables as
      temperature and ionic concentration, as indeed observed using appropriate
      frequency-domain data analysis. The present approach can also be inverted and
      used to test sample homogeneity and quality.

PMID- 15743258
TI  - Pressure dependence of viscosity.
AB  - We reanalyze the pressure dependence of viscosity of liquids of constant
      composition under isothermal conditions. Based exclusively on very general
      considerations concerning the relationship between viscosity and "free volume,"
      we show that, at moderate values of pressure, viscosity increases, as a rule,
      with increasing pressure, provided the liquid is in stable or metastable
      (undercooled) equilibrium states. However, even if the behavior of the viscosity
      is governed by free volume effects, deviations from a positive pressure
      dependence are possible, when the liquid's thermal expansion coefficient is
      negative. We derive an equation that allows one to quantitatively determine the
      pressure dependence of viscosity, which requires, in the simplest case, only the
      knowledge of the temperature dependence of viscosity at constant pressure, the
      thermal expansion coefficient, and the isothermal compressibility of the liquid.
      As an example, the negative pressure dependence of water in the range of
      temperatures 0-4 degrees C and of several silicate liquids, such as albite,
      jadeite, dacite, basalts, etc., could be explained in such a way. Other glass
      forming liquids initially (for moderate pressures) show a positive pressure
      dependence of viscosity that changes to a negative one when subjected to high
      (approximately GPa) isostatic pressure. A detailed analysis of water and already
      mentioned silicate melts at GPa pressures shows that, in addition to free volume
      effects, other pressure induced structural transformations may have to be
      accounted for in a variety of cases. By this reason, the theoretical analysis is
      extended (i) in order to describe the pressure dependence of viscosity for
      systems that are in frozen-in thermodynamic nonequilibrium states (glasses, i.e.,
      undercooled liquids below the glass transition temperature Tg) and (ii) to
      systems which undergo, in addition to variations of the free volume, pressure
      induced changes of other structural parameters. In such cases a decrease of
      viscosity with increasing pressure may occur, in principle, even if the thermal
      expansion coefficient is positive. In this way, the present analysis grants a
      general tool to estimate the pressure dependence of viscosity and supposedly
      settles the controversy in the current literature.

PMID- 15743259
TI  - High temperature structures and orientational disorder in compressed solid
      nitrogen.
AB  - An experimental study of the phase transitions at high temperature in compressed
      solid nitrogen has been performed using Raman spectroscopy. Knowledge of the
      equilibrium phase diagram in the region of the ordered epsilon phase and the two
      disordered delta and deltaloc phases, at pressures between 10 and 20 GPa, has
      been extended up to 500 K. The Raman scattering line shape and line width of the
      active vibrons has been measured accurately, along isobaric scans, across the
      phase transitions. Analysis of the width and of its different behavior with
      increasing temperature in the three phases led to more precise conclusions about
      the nature of the disorder in the different phases. Observation of an evident
      shoulder in the nu2 band of the deltaloc phase suggests the possibility that
      sites of two different symmetries may be occupied by the disk molecules in this
      structure.

PMID- 15743260
TI  - Mechanisms of electron transport through bellows-shaped fullerene tubes.
AB  - A bellows-shaped fullerene tube is featured by diameter modulation along the
      tube, where C60 molecules polymerize with tubular linkages between the molecules.
      The electronic structures of two types of bellows-shaped fullerene tube are
      theoretically found to exhibit band gaps indicating semiconducting
      characteristics. Although the effective masses of the conduction states of the
      two tubes are similar, these states have different spatial distributions. One of
      the two tubes is expected to exhibit thermally assisted electron transport.

PMID- 15743261
TI  - The structure of fluids confined in crystalline slitlike nanoscopic pores.
AB  - Grand canonical and canonical ensemble Monte Carlo simulation methods are used to
      study the structure and phase behavior of Lennard-Jones fluids confined between
      the parallel (100) planes of the face centered cubic crystal. Thin slit pores
      with a width allowing for the formation of only up to five atomic layers are
      considered. The phase diagrams of the systems characterized by different pore
      width as well as by different strength of the fluid-pore walls potential are
      determined. It is shown that an enormously large number of different phase
      diagram topologies can occur, depending on the parameters of the problem (pore
      width, strength of the fluid-pore walls potential, etc).

PMID- 15743262
TI  - Contact atomic structure and electron transport through molecules.
AB  - Using benzene sandwiched between two Au leads as a model system, we investigate
      from first principles the change in molecular conductance caused by different
      atomic structures around the metal-molecule contact. Our motivation is the
      variable situations that may arise in break junction experiments; our approach is
      a combined density functional theory and Green function technique. We focus on
      effects caused by (1) the presence of an additional Au atom at the contact and
      (2) possible changes in the molecule-lead separation. The effects of contact
      atomic relaxation and two different lead orientations are fully considered. We
      find that the presence of an additional Au atom at each of the two contacts will
      increase the equilibrium conductance by up to two orders of magnitude regardless
      of either the lead orientation or different group-VI anchoring atoms. This is due
      to a resonance peak near the Fermi energy from the lowest energy unoccupied
      molecular orbital. In the nonequilibrium properties, the resonance peak manifests
      itself in a negative differential conductance. We find that the dependence of the
      equilibrium conductance on the molecule-lead separation can be quite subtle:
      either very weak or very strong depending on the separation regime.

PMID- 15743263
TI  - Quasiclassical study of Eley-Rideal and hot atom reactions of H atoms with Cl
      adsorbed on a Au(111) surface.
AB  - Using quasiclassical methods and a potential energy surface based on total energy
      calculations, we have found that H atoms react with Cl atoms adsorbed onto a
      Au(111) surface to produce HCl via Eley-Rideal (ER), hot atom (HA), and Langmuir
      Hinschelwood (LH) pathways. We observe two ER mechanisms. At small normal
      incidence energies reaction results from a more or less direct collision with Cl,
      leading to a large amount of product vibration (nu=8), and relatively cold
      rotation and translation. In the second mechanism, more dominant at near-normal
      incidence and/or large incident energies, the H atom passes near Cl, recoils from
      the metal, and is pulled into orbit about Cl. This leads to broader product state
      distributions, and a more even distribution of the 3.0 eV of available energy
      among the product degrees of freedom, similar to products formed via the HA
      pathway. Overall, ER processes tend to contribute less than 10% to the
      reactivity, and most of the HCl is formed via HA processes. There is an increase
      in HCl formation with surface temperature for both the ER and HA mechanisms, but
      this increase is relatively weak. We observe typically about 12% H atom sticking,
      which would lead to HCl formation via a LH process in the experiments, above 140
      K. We observe a weak forward scattering due to the direct ER component, as in the
      experiments. However, unlike the experiments, we observe a dip in our product
      angular distributions about thetaf=0 degrees, which we ascribe to our
      quasiclassical approximation. While we tend to see more energy in the hot
      products than in the experiments, our product translational, rotational, and
      vibrational distributions are in relatively reasonable agreement with those
      measured. One major disagreement with experiment is that there is apparently a
      significant sticking of the H atom at low temperatures, leading to a large LH
      component. In addition, the ER and HA components increase much more strongly with
      temperature than in the calculations. It is possible that electon-hole pair
      excitations in the metal strongly relax both the H atom and the excited HCl
      molecules formed.

PMID- 15743264
TI  - Ethylene-styrene copolymerization with constrained geometry catalysts: a density
      functional study.
AB  - A density functional theory (DFT) study of the ethylene-styrene copolymerization
      process with titanium-based constrained geometry catalyst (CGC) is presented. To
      establish the difference between simplified CGC or real CGC models, i.e.,
      considering all ligands of the catalyst, we have performed calculations for
      ethylene and styrene insertions in both models. Thus, we have used two different
      DFT functional, BP86 and B3L YP along with two basis set, LANL 2DZ (without
      polarization functions) and DZVP (including polarization functions). We have
      noted certain differences between theoretical results published by other authors
      and our theoretical and experimental data.

PMID- 15743265
TI  - Monte Carlo simulations of liquid crystals near rough walls.
AB  - The effect of surface roughness on the structure of liquid crystalline fluids
      near solid substrates is studied by Monte Carlo simulations. The liquid crystal
      is modeled as a fluid of soft ellipsoidal molecules and the substrate is modeled
      as a hard wall that excludes the centers of mass of the fluid molecules. Surface
      roughness is introduced by embedding a number of molecules with random positions
      and orientations within the wall. It is found that the density and order near the
      wall are reduced as the wall becomes rougher, i.e., the number of embedded
      molecules is increased). Anchoring coefficients are determined from fluctuations
      in the reciprocal space order tensor. It is found that the anchoring strength
      decreases with increasing surface roughness.

PMID- 15743266
TI  - Ionic microgels as model systems for colloids with an ultrasoft electrosteric
      repulsion: structure and thermodynamics.
AB  - We present a theoretical analysis of the structural properties and phase behavior
      of spherical, loosely cross-linked ionic microgels that possess a low monomer
      concentration. The analysis is based on the recently derived effective
      interaction potential between such particles [A. R. Denton, Phys. Rev. E 67,
      011804 (2003)]. By employing standard tools from the theory of the liquid state,
      we quantitatively analyze the pair correlations in the fluid and find anomalous
      behavior above the overlap concentration, similar to the cases of star-branched
      neutral and charged polymers. We also employ an evolutionary algorithm in order
      to predict the crystalline phases of the system without any a priori assumptions
      regarding their symmetry class. A very rich phase diagram is obtained, featuring
      two reentrant melting transitions and a number of unusual crystal structures. At
      high densities, both the Hansen-Verlet freezing criterion [J.-P. Hansen and L.
      Verlet, Phys. Rev. 184, 151 (1969)] and the Lindemann melting criterion [F. A.
      Lindemann, Phys. Z. 11, 609 (1910)] lose their validity. The topology of the
      phase diagram is altered when the steric interactions between the polymer
      segments become strong enough, in which case the lower-density reentrant melting
      disappears and the region of stability of the fluid is split into two
      disconnected domains, separated by intervening fcc and bcc regions.

PMID- 15743267
TI  - Effects of colloid polydispersity on the phase behavior of colloid-polymer
      mixtures.
AB  - We study theoretically the equilibrium phase behavior of a mixture of
      polydisperse hard-sphere colloids and monodisperse polymers, modeled using the
      Asakura-Oosawa model [S. Asakura and F. Oosawa, J. Chem. Phys. 22, 1255 (1954)]
      within the free volume approximation of H. N. W. Lekkerkerker, W. C. K. Poon, P.
      N. Pusey, A. Stroobants, and P. B. Warren [Europhys. Lett. 20, 559 (1992)]. We
      compute full phase diagrams in the plane of colloid and polymer volume fractions,
      using the moment free energy method. The intricate features of phase separation
      in pure polydisperse colloids combine with the appearance of polymer-induced gas
      liquid coexistence to give a rich variety of phase diagram topologies as the
      polymer-colloid size ratio xi and the colloid polydispersity delta are varied.
      Quantitatively, we find that polydispersity disfavors fluid-solid against gas
      liquid separation, causing a substantial lowering of the threshold value xi(c)
      above which stable two-phase gas-liquid coexistence appears. Phase splits
      involving two or more solids can occur already at low colloid concentration,
      where they may be kinetically accessible. We also analyze the strength of
      colloidal size fractionation. When a solid phase separates from a fluid, its
      polydispersity is reduced most strongly if the phase separation takes place at
      low colloid concentration and high polymer concentration, in agreement with
      experimental observations. For fractionation in gas-liquid coexistence we
      likewise find good agreement with experiment, as well as with perturbative
      theories for near-monodisperse systems.

PMID- 15743268
TI  - Composition dependence of bilayer elasticity.
AB  - A previously developed molecular level model for homogeneous lipid bilayers
      [Brannigan and Brown, J. Chem. Phys 120, 1059 (2004)] is extended to allow for
      multiple lipid species. Monte Carlo simulations (including species exchange moves
      for efficient sampling) reveal a variety of mixing behaviors in binary systems.
      Two species are identified that maintain stable, randomly mixed fluid membranes
      at vanishing tension over all possible binary compositions. The thermal and
      elastic properties of membranes formed by these lipids are characterized over the
      full composition range. Equilibrium area at constant tension is nonmonotonic with
      respect to composition, but consistent with that of a quadratic mixture. In the
      constant tension ensemble, the bending rigidity of the bilayer is minimized at an
      intermediate composition. The observed functional form of bending rigidity vs
      composition is fit to a simple expression motivated by linear elasticity theory;
      this expression accounts for membrane heterogeneity through a single parameter.

PMID- 15743271
TI  - Prognostic potential of brain natriuretic peptide (BNP) in predialysis chronic
      kidney disease patients.
AB  - In the present study, we investigated the potential of N-BNP (N-terminal B-type
      natriuretic peptide) as a prognostic marker for risk of CV (cardiovascular)
      events, overall mortality and progression to ESRD (end-stage renal disease) in a
      cohort of 83 pre-dialysis CKD (chronic kidney disease) patients without clinical
      evidence of heart failure. During the study, ten patients reached the combined
      end point of overall mortality and/or CV event. Univariate factors associated
      with the combined end point were plasma N-BNP (P < 0.0005), creatinine (P <
      0.002), systolic blood pressure (P < 0.009) and age (P < 0.015). N-BNP levels
      were higher in patients with CV events (P < 0.0005). Cox model regression
      analysis yielded log10 N-BNP (hazard ratio, 9.608; P < 0.007) and pre-existing CV
      disease (hazard ratio, 4.571; P < 0.029) as independent predictors of overall
      mortality or CV events. Kaplan-Meier analysis curves for the subgroup with
      supramedian creatinine levels (225 micromol/l) showed significant separation of
      the curves stratified for plasma N-BNP levels above and below the group median
      (291 pmol/l) for all end points. Receiver-operator-characteristic curves for N
      BNP (355 pmol/l cut-off) demonstrated a specificity of 65.8% at a sensitivity of
      100% for predicting CV events/overall mortality. The measurement of plasma N-BNP
      may aid in the risk stratification of pre-dialysis CKD patients. The high
      sensitivity and negative predictive value (100%) may enable the selection of
      patients who could safely be excluded from further investigations, resulting in
      better focusing of resources.

PMID- 15743272
TI  - Modification degrees at specific sites on heparan sulphate: an approach to
      measure chemical modifications on biological molecules with stable isotope
      labelling.
AB  - Chemical modification of biological molecules is a general mechanism for cellular
      regulation. A quantitative approach has been developed to measure the extent of
      modification on HS (heparan sulphates). Sulphation on HS by sulphotransferases
      leads to variable sulphation levels, which allows cells to tune their affinities
      to various extracellular proteins, including growth factors. With stable isotope
      labelling and HPLC-coupled MS, modification degrees at various O-sulphation sites
      could be determined. A bovine kidney HS sample was first saturated in vitro with
      34S by an OST (O-sulphotransferase), then digested with nitrous acid and analysed
      with HPLC-coupled MS. The 34S-labelled oligosaccharides were identified based on
      their unique isotope clusters. The modification degrees at the sulphotransferase
      recognition sites were obtained by calculating the intensities of isotopic peaks
      in the isotope clusters. The modification degrees at 3-OST-1 and 6-OST-1 sites
      were examined in detail. This approach can also be used to study other types of
      chemical modifications on biological molecules.

PMID- 15743273
TI  - Molecular cloning and characterization of a novel beta-1,3-xylanase possessing
      two putative carbohydrate-binding modules from a marine bacterium Vibrio sp.
      strain AX-4.
AB  - We cloned a novel beta-1,3-xylanase gene, consisting of a 1728-bp open reading
      frame encoding 576 amino acid residues, from a marine bacterium, Vibrio sp.
      strain AX-4. Sequence analysis revealed that the beta-1,3-xylanase is a modular
      enzyme composed of a putative catalytic module belonging to glycoside hydrolase
      family 26 and two putative carbohydrate-binding modules belonging to family 31.
      The recombinant enzyme hydrolysed beta-1,3-xylan to yield xylo-oligosaccharides
      with different numbers of xylose units, mainly xylobiose, xylotriose and
      xylotetraose. However, the enzyme did not hydrolyse beta-1,4-xylan, beta-1,4
      mannan, beta-1,4-glucan, beta-1,3-xylobiose or p-nitrophenyl-beta-xyloside. When
      beta-1,3-xylo-oligosaccharides were used as the substrate, the kcat value of the
      enzyme for xylopentaose was found to be 40 times higher than that for
      xylotetraose, and xylotriose was extremely resistant to hydrolysis by the enzyme.
      A PSI-BLAST search revealed two possible catalytic Glu residues (Glu-138 as an
      acid/base catalyst and Glu-234 as a nucleophile), both of which are generally
      conserved in glycoside hydrolase superfamily A. Replacement of these two
      conserved Glu residues with Asp and Gln resulted in a significant decrease and
      complete loss of enzyme activity respectively, without a change in their CD
      spectra, suggesting that these Glu residues are the catalytic residues of beta
      1,3-xylanase. The present study also clearly shows that the non-catalytic
      putative carbohydrate-binding modules play an important role in the hydrolysis of
      insoluble beta-1,3-xylan, but not that of soluble glycol-beta-1,3-xylan.
      Furthermore, repeating a putative carbohydrate-binding module strongly enhanced
      the hydrolysis of the insoluble substrate.

PMID- 15743274
TI  - Thiol-disulphide interchange in tubulin: kinetics and the effect on
      polymerization.
AB  - All 20 cysteine residues are accessible to disulphide reagents in the tubulin
      dimer, whereas only four are accessible in taxol-stabilized microtubules.
      Reaction rates with disulphide reagents are a function of the reagent, are
      decreased by G nucleotides, and increased with increase in pH and urea. With
      transient (stop-flow) kinetics, DTNB [5,5'-dithiobis-(2-nitrobenzoic acid)] and
      2,2'-dithiodipyridine progress curves cannot be fitted by the sum of exponential
      terms based only on classes of cysteines. The mixed disulphide products react
      further to form both intra- and intermonomer disulphide bonds that can be
      reversed by reducing agents. With MMTS (methyl methanethiosulphonate) or ODNB (n
      octyl-dithio-2-nitrobenzoate), virtually no protein-protein disulphide bonds are
      formed and the ODNB reaction can be given as the sum of three exponential terms
      with pseudo-first-order rate constants of 0.206, 0.069 and 0.010 s(-1) at pH 6.5,
      suggesting three classes of thiol reactivities. Limited cysteine substitution
      leads to only small changes in tryptophan or CD spectra, whereas complete
      substitution leads to loss of the helix content. MMTS-induced loss of SH groups
      leads to progressive increases in the critical concentration and loss of
      polymerization competence that can be reversed by assembly promoters such as
      higher protein concentration, taxol or high ionic strength. Under such
      conditions, the substituted tubulin forms protofilament-based structures such as
      microtubules, open tubules, sheets and/or bundles.

PMID- 15743276
TI  - Treatment of depression improves physical functioning in older adults.
AB  - OBJECTIVES: To determine the effect of collaborative care management for
      depression on physical functioning in older adults. DESIGN: Multisite randomized
      clinical trial. SETTING: Eighteen primary care clinics from eight healthcare
      organizations. PARTICIPANTS: One thousand eight hundred one patients aged 60 and
      older with major depressive disorder. INTERVENTION: Patients were randomized to
      the Improving Mood: Promoting Access to Collaborative Treatment (IMPACT)
      intervention (n=906) or to a control group receiving usual care (n=895). Control
      patients had access to all health services available as part of usual care.
      Intervention patients had access for 12 months to a depression clinical
      specialist who coordinated depression care with their primary care physician.
      MEASUREMENTS: The 12-item short form Physical Component Summary (PCS) score
      (range 0-100) and instrumental activities of daily living (IADLs) (range 0-7).
      RESULTS: The mean patient age was 71.2, 65% were women, and 77% were white. At
      baseline, the mean PCS was 40.2, and the mean number of IADL dependencies was
      0.7; 45% of participants rated their health as fair or poor. Intervention
      patients experienced significantly better physical functioning at 1 year than
      usual-care patients as measured using between-group differences on the PCS of
      1.71 (95% confidence interval (CI)=0.96-2.46) and IADLs of -0.15 (95% CI=-0.29 to
      -0.01). Intervention patients were also less likely to rate their health as fair
      or poor (37.3% vs 52.4%, P<.001). Combining both study groups, patients whose
      depression improved were more likely to experience improvement in physical
      functioning. CONCLUSION: The IMPACT collaborative care model for late-life
      depression improves physical function more than usual care.

PMID- 15743275
TI  - Interaction of the endothelial nitric oxide synthase with the CAT-1 arginine
      transporter enhances NO release by a mechanism not involving arginine transport.
AB  - eNOS (endothelial nitric oxide synthase) catalyses the conversion of L-arginine
      into L-citrulline and NO. Evidence has been presented previously that eNOS is
      associated with the CAT (cationic amino acid transporter)-1 arginine transporter
      in endothelial caveolae, and it has been proposed that eNOS-CAT-1 association
      facilitates the delivery of extracellular L-arginine to eNOS. Definitive proof of
      a protein-protein interaction between eNOS and CAT-1 is lacking, however, and it
      is also unknown whether the two proteins interact directly or via an adaptor
      protein. In the present study, we raised a polyclonal antibody against CAT-1, and
      show using reciprocal co-immunoprecipitation protocols that eNOS and CAT-1 do
      indeed form a complex in BAECs (bovine aortic endothelial cells). In vitro
      binding assays with GST (glutathione S-transferase)-CAT-1 fusion proteins and
      eNOS show that the two proteins interact directly and that no single CAT-1
      intracellular domain is sufficient to mediate the interaction. Overexpression of
      CAT-1 in BAECs by adenoviral-mediated gene transfer results in significant
      increases in both L-arginine uptake and NO production by the cells. However,
      whereas increased L-arginine transport is reversed completely by the CAT-1
      inhibitor, L-lysine, increased NO release is unaltered, suggesting that NO
      production in this in vitro model is independent of CAT-1-mediated transport.
      Furthermore, eNOS enzymic activity is increased in lysates of CAT-1
      overexpressing cells accompanied by increased phosphorylation of eNOS at Ser-1179
      and Ser-635, and decreased association of eNOS with caveolin-1. Taken together,
      these data suggest that direct interaction of eNOS with CAT-1 enhances NO release
      by a mechanism not involving arginine transport.

PMID- 15743277
TI  - Change in sensory functioning predicts change in cognitive functioning: results
      from a 6-year follow-up in the maastricht aging study.
AB  - OBJECTIVES: To examine the longitudinal relationship between sensory functioning
      and a broad range of cognitive functions after 6 years follow-up and whether
      cataract surgery or first-time hearing aid use affected cognition. DESIGN:
      Hierarchical regression procedures were employed to determine whether sensory
      functioning was predictive of cognitive performance. SETTING: Maastricht
      University and the University Hospital Maastricht, the Netherlands. PARTICIPANTS:
      Older Dutch adults (>/=55) enrolled in the Maastricht Aging Study (N=418).
      MEASUREMENTS: Visual and auditory acuity, the Visual Verbal Learning Test (VVLT),
      the Stroop Color Word Test (SCWT), the Concept Shifting Task (CST), the Verbal
      Fluency Test, and the Letter-Digit Substitution Test (LDST). RESULTS: A change in
      visual acuity was associated with change in most cognitive measures, including
      the total and recall scores of the VVLT, the mean score of the first two SCWT
      cards, the mean score of the first two CST cards and the LDST. In addition, a
      change in auditory acuity predicted change in memory performance (VVLT total and
      recall scores), and auditory acuity measured at baseline predicted change in the
      mean score of the first two SCWT cards and the LDST. CONCLUSION: The findings
      support the notion of a strong connection between sensory acuity in auditory and
      visual domains and cognitive performance measures, both from a cross-sectional
      and a longitudinal perspective. They also suggest that it is essential to screen
      older individuals in a clinical context for sensory functioning so that changes
      in visual or auditory acuity are not interpreted as changes in cognitive
      performance.

PMID- 15743278
TI  - Homocysteine and cognitive function in a population-based study of older adults.
AB  - OBJECTIVES: To assess the relations between homocysteine levels and
      neurobehavioral test scores representing a broad range of cognitive domains in a
      population-based study of older adults. DESIGN: Cross-sectional analysis of first
      visit data of subjects in the Baltimore Memory Study, a longitudinal study.
      SETTING: Specific neighborhoods in Baltimore. PARTICIPANTS: Participants were
      1,140 randomly selected residents aged 50 to 70 with a mean age+/-standard
      deviation of 59.3+/-5.9; 65.9% were female, and 54.2% were white and 41.1%
      African-American. MEASUREMENTS: Twenty neurobehavioral test scores in eight
      cognitive domains. RESULTS: Linear regression models revealed that homocysteine
      was consistently and strongly associated with worse neurobehavioral test
      performance, in crude analysis and after control for a large set of important
      covariates. Associations were observed in all eight cognitive domains assessed
      but were strongest and most consistent in the domains of simple motor and
      psychomotor speed, eye-hand coordination/manual dexterity, and verbal memory and
      learning. On average, an increase in homocysteine levels from the 25th to the
      75th percentile, all in the generally accepted normal range, was equivalent in
      its association with neurobehavioral test scores to an increase of 4.2 years of
      age. Logistic regression models revealed that, on average, for the
      neurobehavioral tests associated with homocysteine, subjects in the highest
      quartile of homocysteine levels were more than two times as likely to be in the
      lowest quartile of neurobehavioral test scores as those in the lowest quartile.
      CONCLUSION: Higher homocysteine levels were associated with worse function across
      a broad range of cognitive domains, and the magnitude of the associations was
      large. The data suggest that homocysteine may be a potentially important
      modifiable cause of cognitive dysfunction.

PMID- 15743279
TI  - Accuracy of self-reported depression in persons with dementia.
AB  - OBJECTIVES: To investigate the reliability and validity of self-reported
      depression in demented elderly patients. DESIGN: This is the first study to
      combine the use of multiple depression criteria with dementia and depression
      control groups. SETTING: Houston Veterans Affairs nursing home and
      geropsychiatric inpatient unit and outpatient clinic, Baylor College of
      Medicine's Alzheimer's Disease Research Center. PARTICIPANTS: The total sample
      included 121 volunteer participants, their informants, and their clinicians,
      forming four diagnostic groups (27 controls, 37 dementia only, 28 depression
      only, 29 dementia and depression). MEASUREMENTS: Scales assessing depression,
      deficit awareness, physical illness, functional disability, caregiver burden, and
      severity of cognitive impairment were used. RESULTS: Analyses of variance using
      informant- and clinician-rated depression categories found main effects on
      patient-reported depression scores for deficit awareness and depression diagnosis
      but not for dementia diagnosis. Chi-square analyses revealed that demented and
      depressed patients underreported depression at similarly high rates compared with
      clinician and informant reports. Regression analyses revealed that deficit
      awareness accounted for significant variance in self-reported depression
      accuracy, whereas clinician- or informant-rated depression, severity of cognitive
      impairment, physical disability, functional status, and caregiver burden were not
      significant. CONCLUSION: The results of this investigation suggest that the
      presence of dementia per se does not predict inaccurate depression self-reports.
      Deficit awareness, which covaries with dementia, appears to account for the
      majority of the variance in self-report accuracy. These findings were stable
      across informant- and clinician-rated depression criteria and multiple analyses.

PMID- 15743280
TI  - African-American and white caregivers of older adults with dementia: differences
      in depressive symptomatology and psychotropic drug use.
AB  - OBJECTIVES: To examine relationships between race and psychotropic drug use
      (antidepressant, antianxiety, sedative/hypnotic agents) in informal caregivers
      with symptoms of depression who provide care for elderly relatives with
      progressive dementia. Whether racial differences in medication use relate to
      racial differences on predisposing, enabling, and need factors associated with
      use of these agents was also examined. DESIGN: National survey. SETTING:
      Community-based population of informal caregivers of elderly male U.S. veterans
      with dementia living throughout the 48 contiguous states and Puerto Rico.
      PARTICIPANTS: Two thousand thirty-two African-American and white female
      caregivers of elderly male veterans diagnosed with probable Alzheimer's disease
      or vascular dementia. MEASUREMENTS: Depressive symptoms were measured using a
      modified version of the Center for Epidemiological Studies Depression Scale.
      Antidepressant, antianxiety, and sedative/hypnotic agents were indexed using the
      Veterans Affairs medication classification system. RESULTS: Of caregivers with
      depressive symptoms, 19% used antidepressants, 23% antianxiety agents, and 2%
      sedative/hypnotics. African-American caregivers with depressive symptoms were
      significantly less likely than whites with depressive symptoms to be using
      antidepressants and antianxiety medications. Caregivers who reported higher
      levels of social support and more physician visits during the previous 6 months
      were significantly more likely than others to be taking antidepressants.
      CONCLUSION: This study found that 81% of caregivers with depressive symptoms were
      not taking antidepressant medication and that African-American caregivers were
      less likely than whites to be taking antidepressants. Results suggest that
      routine screening for depression in dementia caregivers may identify unmet needs
      for antidepressant therapy. Particular care should be taken to ensure that
      African-American caregivers are made aware of the potential benefits of such
      therapy.

PMID- 15743281
TI  - Consequences of preventing delirium in hospitalized older adults on nursing home
      costs.
AB  - OBJECTIVES: To determine whether costs of long-term nursing home (NH) care for
      patients who received a multicomponent targeted intervention (MTI) to prevent
      delirium while hospitalized were less than for those who did not receive the
      intervention. DESIGN: Longitudinal follow-up from a randomized trial. SETTING:
      Posthospital discharge settings: community-based care and NHs. PARTICIPANTS:
      Eight hundred one hospitalized patients aged 70 and older. MEASUREMENTS: Patients
      were followed for 1 year after discharge, and measures of NH service use and
      costs were constructed. Total long-term NH costs were estimated using a two-part
      regression model and compared across intervention and control groups. RESULTS: Of
      the 400 patients in the intervention group and 401 patients in the matched
      control group, 153 (38%) and 148 (37%), respectively, were admitted to a NH
      during the year, and 54 (13%) and 51 (13%), respectively, were long-term NH
      patients. The MTI had no effect on the likelihood of receiving long-term NH care,
      but of patients receiving long-term NH care, those in the MTI group had
      significantly lower total costs, shorter length of stay and lower cost per
      survival day. Adjusted total costs were $50,881 per long-term NH patient in the
      MTI group and $60,327 in the control group, a savings of 15.7% (P=.01).
      CONCLUSION: Active methods to prevent delirium are associated with a 15.7%
      decrease in long-term NH costs. Shorter length of stay of patients receiving long
      term NH services was the primary source of these savings.

PMID- 15743282
TI  - Executive function correlates with walking speed in older persons: the InCHIANTI
      study.
AB  - OBJECTIVES: To study the association between performance on psychological tests
      of executive function and performance on lower extremity tasks with different
      attentional demands in a large sample of nondemented, older adults. DESIGN: Cross
      sectional study. SETTING: Community-based. PARTICIPANTS: Nine hundred twenty-six
      persons aged 65 and older, without dementia, stroke, parkinsonism, visual
      impairment, or current treatment with neuroleptics, enrolled in a large
      epidemiological study. MEASUREMENTS: Trail Making Test (TMT) parts A and B and
      two performance-based measures of lower extremity function that require different
      executive/attentional-demanding skills: walking speed on a 4-m course at usual
      pace and walking speed on a 7-m obstacle course at fast pace. A difference score
      (Delta TMT), obtained by subtracting time to perform part A from time to perform
      part B of the TMT, was used as an indicator of executive function. Based on Delta
      TMT, subjects were divided into poor performance, intermediate performance, and
      good performance. RESULTS: After adjustment, no association between Delta TMT and
      4-m course usual-pace walking speed was found. Participants with poor Delta TMT
      and with intermediate Delta TMT performance were more likely to be in the lowest
      tertile for 7-m obstacle course walking speed. CONCLUSION: In nondemented older
      persons, executive function is independently associated with tasks of lower
      extremity function that require high attentional demand.

PMID- 15743284
TI  - Surgical outcomes for patients aged 80 and older: morbidity and mortality from
      major noncardiac surgery.
AB  - OBJECTIVES: To gather information about surgical outcomes for patients in their
      80s and 90s. DESIGN: Prospective cohort study. SETTING: Veterans Affairs Medical
      Centers. PARTICIPANTS: Patients (26,648 aged >/=80; 568,263 aged <80) enrolled in
      the Veterans Affairs National Surgical Quality Improvement Project (NSQIP) who
      had noncardiac surgery between 1991 and 1999. METHODS: Data were collected
      prospectively from medical records and healthcare providers. Detailed information
      was collected about patients' preoperative status, intraoperative experience, and
      postoperative outcomes. Postoperative outcomes were survival status at 30 days
      (deaths from any cause occurring during hospitalization and after hospital
      discharge were captured) and the occurrence of 21 selected surgical complications
      within 30 days postoperatively: wound complications (3 types), respiratory
      complications (4), urinary tract complications (3), nervous system complications
      (3), cardiac complications (3), and other complications (5). MEASUREMENTS:
      Mortality and the occurrence of 21 surgical complications within 30 days of
      surgery. RESULTS: Thirty-day all-cause mortality rates varied widely across
      operations and were higher for patients aged 80 and older than for younger
      patients (8% vs 3%, P<.001). Mortality rates for those aged 80 and older were
      less than 2% for many commonly performed operations (e.g., transurethral
      prostatectomy, hernia repair, knee replacement, carotid endarterectomy). Of
      patients aged 80 and older, 20% had one or more postoperative complications, and
      patients who suffered complications had higher 30-day mortality than those who
      did not (26% vs 4%, P<.001). For 11 of the 21 complications, mortality for
      patients aged 80 and older was greater than 33%. The risk factors for poor
      outcomes were the same for older and younger patients, and the NSQIP Mortality
      Risk model performed well on patients aged 80 and older (C statistic=0.83).
      CONCLUSION: A substantial minority of patients aged 80 and older died or suffered
      a complication within 30 days of surgery, but for many operations mortality rates
      were extremely low. Postoperative complications were associated with high 30-day
      mortality in patients aged 80 and older.

PMID- 15743283
TI  - Exercise leads to faster postural reflexes, improved balance and mobility, and
      fewer falls in older persons with chronic stroke.
AB  - OBJECTIVES: To determine the effect of two different community-based group
      exercise programs on functional balance, mobility, postural reflexes, and falls
      in older adults with chronic stroke. DESIGN: A randomized, clinical trial.
      SETTING: Community center. PARTICIPANTS: Sixty-one community-dwelling older
      adults with chronic stroke. INTERVENTION: Participants were randomly assigned to
      an agility (n=30) or stretching/weight-shifting (n=31) exercise group. Both
      groups exercised three times a week for 10 weeks. MEASUREMENTS: Participants were
      assessed before, immediately after, and 1 month after the intervention for Berg
      Balance, Timed Up and Go, step reaction time, Activities-specific Balance
      Confidence, and Nottingham Health Profile. Testing of standing postural reflexes
      and induced falls evoked by a translating platform was also performed. In
      addition, falls in the community were tracked for 1 year from the start of the
      interventions. RESULTS: Although exercise led to improvements in all clinical
      outcome measures for both groups, the agility group demonstrated greater
      improvement in step reaction time and paretic rectus femoris postural reflex
      onset latency than the stretching/weight-shifting group. In addition, the agility
      group experienced fewer induced falls on the platform. CONCLUSION: Group exercise
      programs that include agility or stretching/weight shifting exercises improve
      postural reflexes, functional balance, and mobility and may lead to a reduction
      of falls in older adults with stroke.

PMID- 15743285
TI  - Dental caries, periodontal disease, and cardiac arrhythmias in community-dwelling
      older persons aged 80 and older: is there a link?
AB  - OBJECTIVES: To examine whether caries or periodontitis is associated with cardiac
      arrhythmias in community-dwelling people aged 80 and older. SETTING: Urban,
      community-based population in Stockholm, Sweden. DESIGN: Cross-sectional.
      PARTICIPANTS: Eligible persons were identified through the Kungsholmen Project,
      which is an ongoing, longitudinal, population-based study of the oldest old. The
      present study included 125 dentate individuals. MEASUREMENTS: Data from
      interviews, a medical examination, and an oral examination. The assessment of
      cardiac arrhythmia was based on a clinical examination by a physician or the
      Stockholm Inpatient Register. Active root caries, active coronal caries, and
      periodontitis were assessed using previously defined National Institute of Dental
      and Craniofacial Research diagnostic criteria. RESULTS: The primary finding of
      the multivariate logistic regression analysis was that persons with three or more
      active root caries lesions had more than twice the odds of cardiac arrhythmias
      than persons without active root caries. The results did not notably change after
      adjusting for age, medications that reduce saliva, and number of teeth. Persons
      with one to two active coronal caries lesions had 2.8 times higher odds (95%
      confidence interval=1.1-7.0) of arrhythmia than persons without active coronal
      caries, but there was no greater risk for persons with three or more coronal
      caries lesions. There was no association between periodontal disease and
      arrhythmia. CONCLUSION: The findings indicate that there may be a link between
      active root caries and cardiac arrhythmias in the oldest old. Nevertheless,
      although a biological pathway is not obvious, it is plausible that both are
      simply markers of declining general health. The results suggest the need for
      further study of these relationships.

PMID- 15743286
TI  - National estimates of medication use in nursing homes: findings from the 1997
      medicare current beneficiary survey and the 1996 medical expenditure survey.
AB  - OBJECTIVES: To provide the first nationwide estimates of medication use in
      nursing homes (NHs) and to introduce a new data set for examining drug use in
      long-term care facilities. DESIGN: Cross-sectional comparison. SETTING: NH
      medication files from two nationally representative data sets, the 1997 Medicare
      Current Beneficiary Survey (MCBS) and the 1996 Medical Expenditure Panel Survey
      Nursing Home Component (MEPS-NHC). PARTICIPANTS: NH residents in the MCBS (n=929,
      weighted n=2.0 million) and MEPS-NHC (n=5,899, weighted n=3.1 million).
      MEASUREMENTS: Estimates include characteristics of facilities and residents,
      average number of drugs used per person per month, and the prevalence and
      duration of use by select therapeutic drug classes. RESULTS: NH residents
      received, on average, seven to eight medications each month (7.6 MCBS, 7.2 MEPS
      NHC). About one-third of residents had monthly drug regimens of nine or more
      medications (31.8% MCBS, 32.4% MEPS-NHC). The most commonly used medications in
      NHs, in descending order, were analgesics and antipyretics, gastrointestinal
      agents, electrolytic and caloric preparations, central nervous system agents,
      anti-infective agents, and cardiovascular agents. CONCLUSION: These estimates
      serve as examples of the first national benchmarks of prescribing patterns in
      NHs. This study highlights the usefulness of the MCBS as an important new
      resource for examining medication use in NHs.

PMID- 15743287
TI  - Economic evaluation of oseltamivir phosphate for postexposure prophylaxis of
      influenza in long-term care facilities.
AB  - OBJECTIVES: To compare the cost-effectiveness of oseltamivir postexposure
      prophylaxis during influenza A outbreaks with that of amantadine postexposure
      prophylaxis or no postexposure prophylaxis in long-term care facilities (LTCFs).
      DESIGN: Cost-effectiveness analysis based on decision analytic model from a
      government-payer perspective. SETTING: A Canadian LTCF, with high staff
      vaccination, at the beginning of influenza season. PARTICIPANTS: Elderly,
      influenza-vaccinated patients living in a Canadian LTCF. MEASUREMENTS:
      Incremental costs (or savings) per influenza-like illness case avoided compared
      with usual care. RESULTS: From a government-payer perspective, this analysis
      showed that oseltamivir was a dominant strategy because it was associated with
      the fewest influenza-like illness cases, with cost savings of $1,249 per 100
      patients in 2001 Canadian dollars compared with amantadine and $3,357 per 100
      patients compared with no prophylaxis. Costs for amantadine dose calculation and
      hospitalization for adverse events contributed to amantadine being a more
      expensive prophylaxis strategy than oseltamivir. Both prophylaxis strategies were
      more cost-effective than no prophylaxis. CONCLUSION: Despite high influenza
      vaccination rates, influenza outbreaks continue to emerge in LTCFs, necessitating
      cost-effective measures to further limit the spread of influenza and related
      complications. Although amantadine has a lower acquisition cost than oseltamivir,
      it is associated with more adverse events, lower efficacy, and individualized
      dosing requirements, leading to higher overall costs and more influenza-like
      illness cases than oseltamivir. Therefore the use of oseltamivir postexposure
      prophylaxis is more cost-effective than the current standard of care with
      amantadine prophylaxis or no prophylaxis.

PMID- 15743288
TI  - Cognitive deficits 3 to 6 years before dementia onset in a population sample: the
      Honolulu-Asia aging study.
AB  - OBJECTIVE: To determine the type of cognitive deficits occurring 3 to 6 years
      before onset of dementia in a population sample. DESIGN: A prospective study in
      which cognitive deficits in participants who had incident dementia at the 6-year
      follow-up were examined at baseline and 3 years. SETTING: Honolulu, Hawaii.
      PARTICIPANTS: Three thousand seven hundred thirty-four Japanese-American men aged
      71 to 93 at baseline. At the 6-year follow-up, there were 52 incident cases of
      dementia, and 1,559 controls. MEASUREMENTS: The Cognitive Abilities Screening
      Instrument (CASI) and a questionnaire on subjective memory problems were
      administered at baseline. Dementia was assessed at baseline and at 3-year and 6
      year follow-ups. RESULTS: Subjects who had incident dementia at 6-year follow-up,
      had showed deficits 3 to 6 years earlier in the CASI domain of episodic memory
      and in the questionnaire covering subjective memory problems. Up to 3 years
      before onset, there was worsening of the episodic memory deficit from baseline
      and new deficits in language, verbal fluency, and orientation. CONCLUSION:
      Cognitive deficits and awareness of memory problems are frequently present
      several years before dementia onset. The predictive value of these deficits is
      not large enough to allow earlier diagnosis of dementia, but information about
      such deficits may be useful as criteria for mild cognitive impairment.

PMID- 15743289
TI  - Disparities in antidepressant treatment in Medicaid elderly diagnosed with
      depression.
AB  - OBJECTIVES: To determine whether there were racial or ethnic disparities in the
      use of antidepressants in low-income elderly patients insured by Medicaid.
      DESIGN: Examination of 1998 Medicaid claims data. SETTING: Centers for Medicare
      and Medicaid Services Medicaid claims data for five U.S. states. PARTICIPANTS:
      All Medicaid recipients aged 65 to 84 with a diagnosis of depression.
      MEASUREMENTS: Treatment versus no treatment; in those treated, treatment with
      drugs was classified as old- or new-generation antidepressants. RESULTS: In 1998,
      7,339 unique individuals aged 65 to 84 had at least one outpatient encounter with
      depression as the primary diagnosis. Nearly one in four (24.2%) received no
      antidepressant drug therapy, and 22% received neither psychotherapy nor an
      antidepressant. African-American individuals were substantially more likely to be
      untreated (37.1%) than Hispanic (23.6%), white (22.4%), or Asian (13.8%)
      individuals. In logistic regression models adjusting for sex, state, long-term
      care status, and age group, African Americans with a primary diagnosis of
      depression were almost twice as likely as whites not to receive an antidepressant
      within the study period (odds ratio=1.91, 95% confidence interval=1.62-2.24).
      Patients in long-term care facilities and those aged 65 to 74 were less likely to
      receive treatment. CONCLUSION: Substantial numbers of elderly Medicaid enrollees
      with a primary diagnosis of depression did not receive antidepressants or
      behavioral therapy. This gap in care disproportionately affected African-American
      patients.

PMID- 15743290
TI  - Atherosclerosis is associated with delirium after coronary artery bypass graft
      surgery.
AB  - OBJECTIVES: To investigate whether atherosclerosis of the ascending aorta,
      internal carotid arteries, and coronary arteries is predictive of postoperative
      delirium in subjects undergoing coronary artery bypass graft (CABG) surgery.
      DESIGN: Prospective cohort study. SETTING: Boston Veterans Affairs Healthcare
      System. PARTICIPANTS: Thirty-six male veterans undergoing primary CABG surgery.
      MEASUREMENTS: Subjects underwent Duplex ultrasound to assess stenosis in the
      internal carotid arteries. Information on the ascending aortic plaque, as
      assessed by transesophageal echocardiogram, and the number of coronary vessels
      bypassed was collected. To create an atherosclerosis score, the number of
      atherosclerotic areas was added. A validated delirium battery was administered to
      the subjects preoperatively and on postoperative Days 2 and 5. RESULTS: Fifteen
      subjects (41.7%) developed delirium postoperatively. In bivariate analysis,
      carotid stenosis of 50% or more (relative risk (RR)=3.5, 95% confidence interval
      (CI)=1.5-8.1) and moderate-severe ascending aortic plaque (RR=2.9, 95% CI=1.0
      8.5) were significantly associated with the development of delirium. There was a
      trend toward a significant association for three or more vessels bypassed
      (RR=9.6, 95% CI=0.6-145.3). After controlling for age, baseline cognition, and
      medical comorbidity, the atherosclerosis score was significantly associated with
      postoperative delirium (adjusted RR=2.7, 95% CI=1.1-6.8). CONCLUSION: In this
      preliminary report, atherosclerosis in the carotid arteries, aorta, and coronary
      circulation is associated with the development of delirium after CABG surgery.
      Further investigation into atherosclerosis as a risk factor for delirium is
      warranted.

PMID- 15743291
TI  - Effect of leg muscle contraction velocity on functional performance in older men
      and women.
AB  - OBJECTIVES: To explore the relationship between impairment (skeletal muscle
      strength and contraction velocity) and function in community-dwelling older
      adults. DESIGN: Cross-sectional. SETTING: University-based human physiology
      laboratory. PARTICIPANTS: One hundred one men and women (aged 75-90).
      MEASUREMENTS: Muscle strength and contraction velocity during bilateral leg press
      (LP) were calculated during one-repetition maximum (1RM) and 40% 1RM. A short
      physical performance battery (SPPB) and gait speed (GS) from a 400-m self-paced
      walk assessed function. Sex differences in LP strength and contraction velocity
      (at 40% 1RM) were assessed. The relationship between these variables and function
      was also examined. RESULTS: Lower extremity strength and contraction velocity
      were significantly associated with GS (P=.02 and P=.005, respectively) and SPPB
      (P<.001 and P=.009, respectively) in men only. Contraction velocity, but not
      muscle strength, was significantly associated with GS (P<.001) and SPPB (P=.02)
      in women. CONCLUSION: Sex differences exist in the relationship between
      impairment (muscle strength and contraction velocity) and function. Older men and
      women may employ different strategies to achieve success on different functional
      tasks. These findings may have important implications for clinicians practicing
      geriatric rehabilitation.

PMID- 15743292
TI  - Pneumonia in nursing home residents: factors associated with in-home care of
      EverCare enrollees.
AB  - OBJECTIVES: To identify determinants of whether nursing home (NH) residents
      enrolled in EverCare were admitted to in-home intensive service days (ISDs)
      rather than a hospital when they were thought to have pneumonia. DESIGN:
      Retrospective cross-sectional. SETTING: EverCare operations in five metropolitan
      areas. PARTICIPANTS: EverCare enrollees admitted to ISDs or a hospital for
      suspected pneumonia in 2002. MEASUREMENTS: Member, nurse practitioner, physician,
      and NH characteristics extracted from EverCare's administrative data and Online
      Survey Certification and Reporting NH data. RESULTS: Multivariable logistic
      regression indicated that admission to ISDs (65% of cases) was positively
      associated with age (odds ratio (OR)=1.04. 95% confidence interval (CI) 1.03
      1.04), advance directives not to hospitalize (OR=2.88, 95% CI=1.76-4.72), or
      perform cardiopulmonary resuscitation, 3.09 (2.44-3.91), and hours worked by the
      NH's registered nurses (OR=4.34, 95% CI=1.74-10.8). Admission to ISD was less
      likely on weekends (OR=0.30, 95% CI=0.21-0.43), when residents had renal
      insufficiency (OR=0.61, 95% CI=0.49-0.76), and when the resident was covered by
      Medicaid (OR 0.87, 95% CI=0.82-0.93). CONCLUSION: Exploration of ways to extend
      services to weekends, increased availability of registered nurse staff, attention
      to advance directives, and a better understanding of the role of Medicaid might
      increase the likelihood of caring for EverCare enrollees with suspected pneumonia
      in their NH.

PMID- 15743293
TI  - Energy requirements are not greater in elderly patients suffering from pressure
      ulcers.
AB  - OBJECTIVES: To estimate energy requirements in diseased elderly patients with
      pressure ulcers (PUs). DESIGN: Open, case-control study. SETTING: University
      Hospital of Angers (France). PARTICIPANTS: Twenty-nine patients with PUs (Norton
      index risk=14.3+/-3.3) and 27 controls hospitalized for various diseases
      (Norton=13.9+/-3.3). MEASUREMENTS: Energy requirements were estimated using
      measured resting metabolic rate (RMR) and multiplied by 1.26 and 1.5 to range
      between minimal World Health Organization (WHO) requirements and those of adults
      undergoing light physical activity. Energy intakes were estimated using 3-day
      food weight records. Measured RMR was compared with the prediction equations of
      Harris-Benedict, WHO, and Schofield. RESULTS: Measured RMR did not differ between
      the two groups (P=.48), and was not related to grade or size of the PUs. The WHO
      equation (82 kcal/d, P=.006) and the Schofield formula (57 kcal/d, P=.05)
      slightly underestimated calculated RMR, but the Harris-Benedict equation (40
      kcal/d, P=.13) accurately estimated it. Energy requirements therefore ranged
      between 1,536+/-340 kcal/d and 1,828+/-405 kcal/d, (25-30 kcal/kg body weight per
      day). Energy intake was lower than energy requirements by 176 to 479 kcal/d.
      CONCLUSION: Diseased elderly patients with PUs do not have greater energy
      expenditure, with their requirements suggested to range between 25 and 30 kcal/kg
      body weight per day. Malnutrition within this population is most likely the
      result of low energy intake.

PMID- 15743294
TI  - Relationship between subjective social status and measures of health in older
      Taiwanese persons.
AB  - OBJECTIVES: To compare the association between subjective ladder ranking and
      health measures with the association between objective indices and health
      measures in older Taiwanese men and women. DESIGN: Cross-sectional study.
      SETTING: A population-representative sample of elderly and nearly elderly men and
      women in Taiwan. PARTICIPANTS: The study included 991 participants from the
      Social Environment and Biomarkers of Aging Study in Taiwan. MEASUREMENTS: The
      information collected included demographic characteristics; subjective ladder
      score of SES; objective measures of SES, including education, income, and
      occupation; health behaviors; health-related variables such as self-rated health,
      basic activity of daily living difficulties, instrumental activity of daily
      living (IADL) difficulties, and physical activity difficulties; and depression
      score. RESULTS: Low ladder score was associated with poorer self-rated health and
      more reported IADL and physical activity difficulties, even after adjustment for
      objective measures of SES and other covariates. The multiply adjusted odds ratio
      for a one-quartile difference in ladder score and worse self-rated health was
      1.19 (95% confidence interval=1.06-1.33). The associations between subjective
      ladder ranking and health status were generally stronger in those who had 6 years
      or less of education than in those who received more education. CONCLUSION: A
      simple subjective assessment of one's ranking on the social hierarchy was
      associated with self-rated health and physical functional status in an older
      ethnic Chinese population. The associations were independent of the effects of
      traditional objective measures of SES, such as education, income, and occupation.

PMID- 15743295
TI  - Multidimensional attitudes of medical residents and geriatrics fellows toward
      older people.
AB  - OBJECTIVES: To examine dimensions of a validated instrument measuring geriatric
      attitudes of primary care residents and performances on these dimensions between
      residents and fellows. DESIGN: Cross-sectional and longitudinal studies. SETTING:
      An academic medical center. PARTICIPANTS: Two hundred thirty-eight primary care
      residents (n=177) and geriatrics fellows (n=61) participated in the study from
      1995 to 2000. MEASUREMENTS: A 14-item, 5-point Likert scale previously validated
      for measuring primary care residents' attitudes toward older people and geriatric
      patient care was used. RESULTS: Factor analysis showed four dimensions of the
      scale, labeled Social Value, Medical Care (MC), Compassion (CP), and Resource
      Distribution, which demonstrated acceptable reliability. Both groups of subjects
      showed significantly (P<.001) positive (mean>3) attitudes across the dimensions
      and times, except for residents, who had near-neutral (mean=3) attitudes on MC.
      Residents' mean attitude scores on the overall scale and the MC and CP subscales
      were significantly (P<.001) lower than those of fellows over time. Residents and
      fellows showed different change patterns in attitudes over time. Residents'
      attitudes generally improved during the first 2 years of training, whereas
      fellows' attitudes declined slightly. Personal experience was a strong predictor
      of residents' attitudes toward older patients. Ethnicity, academic specialty,
      professional experience, and career interest in geriatrics were also associated
      with residents' attitude scores. CONCLUSION: The multidimensional analysis of the
      scale contributes to better understanding of medical trainees' attitudes and
      sheds light on educational interventions.

PMID- 15743296
TI  - Detection of delirium in the intensive care unit: comparison of confusion
      assessment method for the intensive care unit with confusion assessment method
      ratings.
AB  - OBJECTIVES: To compare the Confusion Assessment Method (CAM) and CAM for the
      Intensive Care Unit (CAM-ICU) methods for detecting delirium in alert,
      nonintubated older ICU patients. DESIGN: Comparison study. SETTING: Fourteen-bed
      medical ICU of an 800-bed university teaching hospital. PARTICIPANTS: Twenty-two
      patients aged 65 and older admitted to the ICU. MEASUREMENTS: Two blinded,
      trained clinician-researchers who had undergone interrater reliability testing
      interviewed patients separately, usually within 10 minutes of each other (up to
      120 minutes). Each researcher examined patients for the four key CAM criteria:
      acuteness, inattention, disorganized thinking, and altered level of
      consciousness. One researcher used the CAM method with the Mini-Mental State
      Examination and Digit Span; the other researcher used the CAM-ICU method with
      nonverbal cognitive and attention tasks. RESULTS: Rates of delirium were 68%
      according to CAM and 50% according CAM-ICU. Comparing the two methods, agreement
      was 82%, with a kappa of 0.64. Using the CAM as the reference standard, the CAM
      ICU had a sensitivity of 73% (95% confidence interval (CI)=60-86) and specificity
      of 100% (95% CI=56-100). There were four false-negative ratings using the CAM
      ICU. Reasons for disparate results were that the CAM used more-detailed cognitive
      testing that detected more deficits (3 patients) and the time elapsed (90
      minutes) between ratings in one patient with markedly fluctuating symptoms.
      CONCLUSION: CAM and CAM-ICU agreement was moderately high. Although the CAM-ICU
      is recommended for ICU patients because of its brevity and ease of use, the
      standard CAM method may detect more subtle cases of delirium in nonintubated,
      verbal ICU patients.

PMID- 15743297
TI  - Measuring the psychological outcomes of falling: a systematic review.
AB  - The objectives were to identify fall-related psychological outcome measures and
      to undertake a systematic quality assessment of their key measurement properties.
      A Cochrane review of fall-prevention interventions in older adults was used to
      identify fall-related psychological measurements. PubMed, CINAHL, and PsycINFO
      were systematically searched to identify instruments not used in trials and
      papers reporting the methodological quality of relevant measures. Reference lists
      of articles were searched for additional literature, and researchers were
      contacted. Two reviewers undertook quality extraction relating to content,
      population, reliability, validity, responsiveness, practicality, and feasibility.
      Twenty-five relevant papers were identified. Twenty-three measures met the
      inclusion criteria: six single-item questions, Falls Efficacy Scale (FES),
      revised FES, modified FES, FES-UK, Activities-specific Balance and Confidence
      Scale (ABC), ABC-UK, Confidence in maintaining Balance Scale, Mobility Efficacy
      Scale, adapted FES, amended FES, Survey of Activities and Fear of Falling in the
      Elderly (SAFFE), University of Illinois at Chicago Fear of Falling Measure,
      Concern about Falling Scale, Falls Handicap Inventory, modified SAFFE,
      Consequences of Falling Scale, and Concern about the Consequences of Falling
      Scale. There is limited evidence about the measurement properties of single-item
      measures. Several multiitem measures obtained acceptable reliability and
      validity, but there is less evidence regarding responsiveness, practicality, and
      feasibility. Researchers should select measures based on the constructs they
      intend to study. Further research is needed to establish and compare the
      instruments' measurement properties.

PMID- 15743298
TI  - Geriatrics for residents in the surgical and medical specialties: implementation
      of curricula and training experiences.
AB  - In 1994, under the leadership of the late Dennis Jahnigen, the American
      Geriatrics Society, with support of the John A. Hartford Foundation, began a
      project to improve the amount and quality of geriatrics education that surgical
      and related medical specialty residents receive. The targeted disciplines
      initially were general surgery, emergency medicine, gynecology, orthopedic
      surgery, and urology and, later, anesthesiology, ophthalmology, otolaryngology,
      physical medicine and rehabilitation, and thoracic surgery. A key element of this
      project was to develop model programs within surgical and related specialty
      residency education. The Geriatrics Education for Specialty Residents (GESR)
      program has supported 29 residencies to pilot methods for integration of
      geriatrics within residency programs, encouraged and inspired development of
      curricular content, and helped to develop faculty leaders to support these
      efforts in the long term and at a national level. This paper describes the GESR
      program, the status of curriculum development, steps for other programs to use in
      developing a geriatrics education program, and some of the common barriers likely
      to be encountered during implementation along with solutions to those barriers.

PMID- 15743299
TI  - Faculty development in geriatrics for clinician educators: a unique model for
      skills acquisition and academic achievement.
AB  - As the size of the aged American population increases, so too does the shortage
      of trained providers in geriatrics. Educational strategies to train physicians at
      all levels of experience within adult medical and surgical disciplines are needed
      to complement fellowship training, given the small size of most academic
      faculties in geriatrics. This article describes a unique faculty development
      program that creates geriatrically oriented faculty in multiple disciplines. The
      Boston University Center of Excellence in Geriatrics (COE), funded by the John A.
      Hartford Foundation, has trained 25 faculty members. Four to six scholars enter
      the program each year and participate in the COE 1 day per week. Nine months are
      spent in four content modules-Geriatrics Content, Clinical Teaching, Evidence
      based Medicine, and Health Care Systems; 3 months are spent in supervised
      scholarly activities and clinical settings. A self-report questionnaire and a
      structured interview were used to evaluate the outcomes of participation in the
      COE. The results from the first 4 years of the program are reported. The response
      rate was 83% for the self-report questionnaire and 75% for the structured
      interview. The results indicate that the COE is effective in improving scholars'
      assessment and management of older patients. The structured interview revealed
      that the COE program promotes the integration of geriatrics into clinical
      teaching at the medical student and resident level. Participants also completed
      scholarly projects in geriatrics. This program effectively trains faculty
      scholars to better care for older adults and to teach others to do likewise.

PMID- 15743300
TI  - Care-needs certification in the long-term care insurance system of Japan.
AB  - The introduction of Japan's long-term care insurance (LTCI) system in April 2000
      has made long-term care an explicit and universal entitlement for every Japanese
      person aged 65 and older based strictly on physical and mental status. At the
      start of the program, more than two million seniors were expected to apply for
      services to approximately 3,000 municipal governments, which are the LTCI
      insurers. The LTCI implementation required a nationally standardized needs
      certification system to determine service eligibility objectively, fairly, and
      efficiently. The current computer-aided initial needs-assessment instrument was
      developed based on data collected in a large-scale time study of professional
      caregivers in long-term care institutions. The instrument was subsequently tested
      and validated by assessing data of 175,129 seniors involved in the national model
      programs before the start of LTCI. The computer-aided initial assessment (an 85
      item questionnaire) is used to assign each applicant to one of seven need levels.
      The Care Needs Certification Board, a committee of medical and other
      professionals, reviews the results. Three years after implementation, the LTCI
      system and its needs-assessment/certification system have been well accepted in
      Japan. Despite the overall successes, there remain challenges, including area
      variations, growing demands for services, and the difficulty of keeping the needs
      certification free of politics. The LTCI computer network that links
      municipalities and the central government is instrumental in continuously
      improving the needs-certification system. Future challenges include promoting
      evidence-based system improvements and building incentives into the system for
      various constituencies to promote seniors' functional independence.

PMID- 15743301
TI  - A new paradigm for clinical investigation of infectious syndromes in older
      adults: assessing functional status as a risk factor and outcome measure.
AB  - Adults aged 65 and over comprise the fastest growing segment of the U.S.
      population, and older adults experience greater morbidity and mortality due to
      infection than young adults. While this factor is well established, most clinical
      investigation of infectious diseases in the aged focuses on microbiology, and
      crude endpoints of clinical success such as cure rates or mortality, but often
      fails to assess functional status, a critical variable in geriatric care.
      Functional status can be evaluated as a risk factor for infectious disease or an
      outcome of interest following specific interventions utilizing well-validated
      instruments. This paper outlines the currently available data suggesting a link
      between infection, immunity and impaired functional status in the elderly,
      summarizes commonly employed instruments used to determine specific aspects of
      functional status, and provides recommendations for a new paradigm in which
      clinical trials of older adults include functional assessment.

PMID- 15743302
TI  - Assisted living facilities: American Geriatrics Society position paper.

PMID- 15743303
TI  - Assisted living facilities: optimizing outcomes.

PMID- 15743304
TI  - Optimism and aging.

PMID- 15743305
TI  - The association between successful treatment of depression and physical
      functioning in older people seeking primary care.

PMID- 15743306
TI  - Feasibility of ambulatory overnight oximetry in consecutive patients in a
      dementia clinic.

PMID- 15743307
TI  - An unexpected cause of delirium in an old patient.

PMID- 15743308
TI  - Age-related decline in maximal oxygen capacity: consequences for performance of
      everyday activities.

PMID- 15743309
TI  - More on anticoagulation in older people.

PMID- 15743310
TI  - Spontaneous retroperitoneal hematomas in elderly patients treated with low
      molecular-weight heparins.

PMID- 15743311
TI  - Acupuncture treatment of geriatric patients with ischemic stroke: a randomized,
      double-controlled, single-blind study.

PMID- 15743312
TI  - Beta-blocker use, bone mineral density, and fracture risk in older women: results
      from the Epidemiologie de l'Osteoporose prospective study.

PMID- 15743313
TI  - Insulinoma revealed by recurrent falls in old age.

PMID- 15743314
TI  - An adverse event associated with hip protectors.

PMID- 15743315
TI  - Homicides of disabled older persons by their caregivers in Japan.

PMID- 15743316
TI  - Teaching the older adult.

PMID- 15743317
TI  - Cell cycle regulation and its aberrations in human lung carcinoma.
AB  - Cell cycle is strictly regulated by complex and redundant mechanisms. Basically,
      cell cycle transition is promoted by accelerator molecules termed 'cyclin' and
      'cyclin-dependent kinase' (cdk), and inhibited by brake molecules termed 'cdk
      inhibitor' (CKI). Although based on the results of early experimental studies and
      of clinicopathological analyses, there was much speculation that gene aberration
      of those molecules would be common; this has not turned out to be the case. One
      reason may be that activation or inactivation of a single molecule by itself
      usually does not lead to cell transformation, but rather to apoptosis. Successful
      transformation and unchecked cell proliferation appears to require the
      coordinated up-regulation of cyclin/cdk and/or suppression of CKI. In this
      article, I focus on the precise regulation of the cell cycle and describe
      abnormalities found in these proteins in lung carcinoma. Notable findings in lung
      carcinoma include: (i) cyclin A/cdk2 plays a key role in cell proliferation,
      while protein amount of cyclin E does not necessarily reflect cellular
      proliferative activity, depending on the tumor type; (ii) CKI function not only
      as suppressors, but also as activators of cdk, depending on expression levels;
      and (iii) aberrant expression of cyclin/cdk can lead to apoptosis in vivo in
      humans. Another key point is that as lung carcinoma is composed of a mixture of
      heterogeneous histological subtypes, the growth control of carcinoma cells is
      diversely regulated, depending on each histological subtype. This diversity is
      also described with our experimental results.

PMID- 15743318
TI  - PKC theta, a novel immunohistochemical marker for gastrointestinal stromal tumors
      (GIST), especially useful for identifying KIT-negative tumors.
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the
      digestive tract and the majority of GIST has characteristic gain-of-function
      mutations of the c-kit gene, which encodes the KIT receptor for stem cell factor.
      The present study aimed to establish the usefulness of protein kinase C theta
      (PKC theta) as an immunohistochemical marker for GIST in comparison with KIT
      immunohistochemistry. PKC theta immunohistochemistry was carried out not only on
      48 cases of GIST and another 40 cases of gastrointestinal mesenchymal tumors, but
      also on 24 cases of various tumors known to be immunohistochemically positive for
      KIT. Immunohistochemically, 41 out of 48 cases (85%) of GIST were positive for
      PKC theta, and its expression was confirmed by Western blot analysis using six
      cases of surgically resected GIST. In the present study there were six GIST
      immunohistochemically negative for KIT, which histologically revealed a myxoid
      epithelioid appearance characteristic to that of GIST with platelet-derived
      growth factor receptor alpha mutation. All six GIST were immunohistochemically
      positive for PKC theta. No PKC theta immunoreactivity was observed in other
      gastrointestinal mesenchymal tumors and various KIT-positive tumors except for
      three cases (14%) of gastrointestinal schwannomas. The present study revealed
      that PKC theta is an immunohistochemically novel and useful marker for GIST,
      especially for GIST negative for KIT.

PMID- 15743319
TI  - Significant correlation of morphological remodeling in ulcerative colitis with
      disease duration and between elevated p53 and p21 expression in rectal mucosa and
      neoplastic development.
AB  - Although a chronic inflammation-carcinoma sequence has been proposed in cases of
      longstanding ulcerative colitis (UC), the relationship of morphological
      alteration or remodeling of regenerated mucosa to carcinoma development is yet to
      be clarified. Therefore, mucosae of 49 resected rectae from individuals with UC
      were histologically and quantitatively analyzed, with regard to thickness and
      morphological parameters of crypts, in relation to the disease duration, clinical
      disease activity and neoplastic development. An immunohistochemical examination
      of Ki-67, p53, p21(WAF1) and ssDNA labeling was also included. Significant
      correlations of number, height, angle, fusion and Paneth cell metaplasia of
      crypts, as well as thickness of the muscularis mucosae, were revealed with
      disease duration, as confirmed by three-dimensional reconstructed image analysis.
      p53 and p21(WAF1)-positive cells increased with disease duration and were
      significantly more frequent in cases with neoplasia, suggesting more DNA damage.
      However, this was not the case for ssDNA labeling, assessed as an indicator of
      apoptosis. In general, histological changes and p53, p21(WAF1) and Ki-67 labeling
      were correlated. In conclusion, histological parameters for mucosal remodeling
      correlate well with UC duration, indicating accumulation of structural
      alterations. Accumulated damage to DNA, reflected by increased p53 and p21(WAF1)
      labeling indices, might be involved in cancer development, as well as
      longstanding inflammation.

PMID- 15743321
TI  - Increased norepinephrine-associated adrenomedullary inclusions in Parkinson's
      disease.
AB  - The association with Parkinson's disease (PD) of adrenomedullary inclusions,
      known as 'hyaline globules' or 'adrenal bodies', has been reported for over 35
      years. However, the common perception has been that adrenomedullary chromaffin
      cells cannot be recognized as pathological cells in PD. In the present study, we
      discovered that the number of adrenomedullary inclusions per unit area of the
      adrenal medulla was larger in PD and other Lewy body disorders (LBD) than in
      other neurological diseases and controls without any autonomic dysfunctions, and
      correlated with the duration of LBD. We also showed that the cells with
      adrenomedullary inclusions are all norepinephrine-secreting chromaffin cells.
      This was detected by PAS reaction following peroxidase immunohistochemistry of
      four proteins: chromogranin A, phenylethanolamine N-methyltransferase, S-100
      protein and neurofilament protein. We also proved that the components of
      adrenomedullary inclusions are immunocytochemically different from those of Lewy
      bodies and Lewy-related neurites, as adrenomedullary inclusions were
      immunonegative to ubiquitin and alpha-synuclein as well as to the above four
      proteins. Therefore, contrary to current opinion, the norepinephrine-secreting
      adrenomedullary chromaffin cell is indeed another type of pathological cell in PD
      and other LBD.

PMID- 15743320
TI  - Immunohistochemical analysis of cleaved caspase-3 detects high level of apoptosis
      frequently in diffuse large B-cell lymphomas of the central nervous system.
AB  - The purpose of the present paper was to examine the level of apoptosis and the
      relationships among apoptosis, apoptosis-associated proteins, and proliferating
      potential in lymphoma tissues to clarify the characteristics of apoptosis in
      diffuse large B-cell lymphomas (DLBCL) of the central nervous system (CNS). The
      formalin-fixed, paraffin-embedded tissues of CNS and non-CNS DLBCL (20 cases
      each) were studied by terminal deoxynucleotidyl transferase-mediated dUTP-nick
      end labeling (TUNEL) and immunohistochemistry, using antibodies against single
      stranded DNA (ssDNA), cleaved caspase-3, bcl-2, bax, p53, Fas and Ki-67. The
      cleaved caspase-3 immunohistochemistry detected apoptosis of the lymphoma cells
      most sensitively compared to TUNEL and ssDNA immunohistochemistry. High
      expression (grade + + or + + +) of cleaved caspase-3 was found more frequently in
      CNS DLBCL (11 cases, 55%) than non-CNS DLBCL (three cases, 15%; P = 0.009). Bax
      positivity of lymphoma cells was increased in six cases of CNS DLBCL, which also
      showed high positivity of cleaved caspase-3. There was no significant correlation
      between the cleaved caspase-3-positivity and the Ki-67 positivity. The present
      study indicates that the number of apoptotic cells and expression level of
      cleaved caspase-3 were significantly higher in CNS DLBCL than non-CNS DLBCL, and
      that the correlation of bax and cleaved caspase-3 expression was often present in
      CNS DLBCL.

PMID- 15743322
TI  - Lung pathology of pale ear mouse (model of Hermansky-Pudlak syndrome 1) and beige
      mouse (model of Chediak-Higashi syndrome): severity of giant lamellar body
      degeneration of type II pneumocytes correlates with interstitial inflammation.
AB  - The authors have recently reported the presence of characteristic foamy
      swelling/degeneration (giant lamellar body degeneration, GLBD) of type II
      pneumocytes in the lungs affected by Hermansky-Pudlak syndrome (HPS)-associated
      interstitial pneumonia (HPSIP), and proposed the hypothesis that GLBD may be the
      triggering factor in the development of HPSIP (Virchows Arch 2000; 437: 304-13).
      The purpose of the present paper was to investigate the lung pathology of pale
      ear (ep) mouse, a mouse model of HPS1, and of beige (bg) mouse, a mouse model of
      Chediak-Higashi syndrome (CHS) with a reference to GLBD and associated pathologic
      changes. GLBD was found in both ep and bg mice soon after birth, and increased in
      severity as the mice grew older. Younger mice had only GLBD with no evidence of
      interstitial change. Aged bg mice showed the most prominent GLBD and patchy areas
      of alveolar collapse accompanied by lymphocytic infiltration and slight fibrosis.
      Aged ep mice with less severe GLBD than bg mice of comparable ages also had a
      slight tendency to develop interstitial inflammation but no fibrosis. The
      pneumocytes with GLBD were immunoreactive for surfactant protein B and composed
      of giant lamellar bodies ultrastructurally, findings which were almost identical
      to those of human GLBD. The results of the present study support the hypothesis
      that GLBD may play an important role in the development of HPSIP. Ep and bg mice,
      especially the latter, may be useful mouse models of HPSIP.

PMID- 15743323
TI  - Catastrophic antiphospholipid syndrome: a rare cause of disseminated
      microvascular thrombotic injury - a case report with pathological and molecular
      correlative studies.
AB  - Catastrophic antiphospholipid syndrome (CAPS) is a severe and rare variant of
      antiphospholipid syndrome (APS) characterized by acute multiorgan failure due to
      small vessel thrombi in patients with positive antiphospholipid antibodies. We
      report a fatal case of catastrophic antiphospholipid syndrome in a young woman
      with a history of polymyositis and Hodgkin lymphoma. The patient was admitted to
      hospital because of severe foot pain following several weeks of skin ulcerations.
      Doppler ultrasonography showed evidence of arterial ischemia of the both lower
      extremities. Despite anticoagulation, immunosuppression, plasmapheresis and
      antibiotic therapy, she developed cutaneous gangrene, retroperitoneal hematoma,
      ileus, and acute respiratory and renal failure that resulted in death. Autopsy
      showed multifocal vascular injury and microthrombi with associated hemorrhages
      and infarcts in multiple organs. The patient had normal levels of functional
      protein C and protein S and a normal level of plasma homocysteine. Tests for
      common thromophilic gene mutations including prothrombin 20210, factor V Leiden
      1691, and methylene tetrahydrofolate reductase 677 were negative. To our
      knowledge, this is the first CAPS patient with molecular studies for genetic
      prothrombotic mutations. Our report showed that there was no association between
      the development of CAPS and inherited thromophilia.

PMID- 15743324
TI  - Clear cell type of renal cell carcinoma with numerous hyaline globules: a
      diagnostic pitfall.
AB  - A unique and never-before-published example of clear cell renal cell carcinoma
      (CRCC) found among 9000 primary renal cell tumors is presented. The tumor
      contained such a dense concentration of glassy hyaline globules (GHG) in the
      cytoplasm of the neoplastic cells that it overshadowed the morphology of the
      neoplasm. The resulting appearance of the tumor was quite misleading and
      different from the conventional CRCC. The GHG were 7-30 microm in diameter. They
      were glassy and pale to slightly eosinophilic in color in hematoxylin-eosin. The
      GHG stained positively with periodic acid-Schiff and negatively with silver and
      Hale's colloidal iron. Immunohistochemically, they were also negative for anti
      Mycobacterium bovis antigen. At the ultrastructural level, the GHG were formed by
      an amorphous mass of stellate shape. The GHG were localized within rough
      endoplasmic reticulum. Molecular genetically, mutation of the distal part of exon
      3 of the VHL gene causing elongation of the VHL protein was found in the tumor,
      thus confirming the diagnosis of CRCC.

PMID- 15743325
TI  - Soft-tissue angiomatosis in adulthood: a case in the forearm showing a prominent
      myxoid adipose tissue component mimicking liposarcoma.
AB  - Soft-tissue angiomatosis is a rare condition characterized by diffuse
      proliferation of benign vascular structures, accompanied by mature adipose
      tissue, which affect a large segment of the body in a contiguous fashion. Most
      patients present in childhood or adolescence. We report a case of large soft
      tissue angiomatosis, located in the left forearm of a 65-year-old man, which
      showed extensive intramuscular and intermuscular infiltration, and embracement of
      the radius and the main vascular and neural bundles of the forearm. Due to the
      deep location, large size, ill-defined limits and non-homogeneous composition
      with areas suggestive of an adipose component in the radiological examination,
      the lesion raised the possibility clinically of a liposarcoma. The myxoid adipose
      tissue component of the lesion, a feature previously undescribed, and the
      predominance of small, capillary-sized vessels were considered concordant with
      the clinical diagnosis. This presentation is rare. The features of the lesion
      made complete surgical excision impossible and amputation of the extremity was
      considered the best treatment. The main differential diagnoses include
      infiltrating lipoma, myxolipoma, angiomyxolipoma, angiolipoma, intramuscular
      angioma, liposarcoma and low-grade myxofibrosarcoma. In conclusion, angiomatosis
      might simulate liposarcoma, particularly if the mass is large, heterogeneous,
      myxoid and appears later in life.

PMID- 15743326
TI  - Colonic lipoma with florid vascular proliferation and nodule-aggregating
      appearance related to repeated intussusception.
AB  - A unique case of repeatedly intussuscepted colonic lipoma mimicking an epithelial
      tumor in a 50-year-old man is reported. The tumor was located in the ascending
      colon and was approximately 5 cm in diameter. Colonoscopic and barium-enema
      examinations suggested a huge epithelial tumor because of its nodule-aggregating
      appearance. In contrast, computed tomography examination showed a fatty element
      in the core of the lesion. The biopsy specimens suggested a primary angiomatous
      lesion because of its pronounced vascular proliferation. Because the presumed
      diagnoses based on the examinations were different, the preoperative diagnosis
      was not confirmed. The tumor was composed of intramural lipoma with a multiple
      polypoid mucosa overlay. This lesion was unique in that the lipoma appeared to be
      within the muscularis propria and the multiple polypoid appearance of its
      covering mucosa. The mucosal changes including florid vascular proliferation,
      fibromuscular obliteration and epithelial regeneration suggested a reparative
      process, with ischemic damage due to the effects of intussusception being the
      most likely event. It should be kept in mind that even a simple lipoma can have a
      unique appearance reminiscent of epithelial tumor when it repeatedly experiences
      intussusception.

PMID- 15743327
TI  - Less effective executive functioning after one night's sleep deprivation.
AB  - The prefrontal cortex (PFC) is affected negatively by sleep deprivation (SD) and
      executive functioning is largely dependent on activity in the PFC. Earlier
      studies have focused on subsystems of executive functioning, and tests of
      executive functioning have shown both low reliability and low validity. In the
      present study, 11 healthy volunteers were sleep deprived and compared with 11
      healthy controls in a study on effects of one night's SD on integrative executive
      functioning. Following SD, the performance of subjects on an ecologically valid
      test, the modified Six Elements Test, was significantly impaired. There were no
      group differences on psychomotor vigilance, verbal or visuo-spatial working
      memory. This extends previous knowledge of performance effects of SD, and may be
      of special importance for individuals with cognitive work tasks.

PMID- 15743329
TI  - Impaired alertness and performance driving home from the night shift: a driving
      simulator study.
AB  - Driving in the early morning is associated with increased accident risk affecting
      not only professional drivers but also those who commute to work. The present
      study used a driving simulator to investigate the effects of driving home from a
      night shift. Ten shift workers participated after a normal night shift and after
      a normal night sleep. The results showed that driving home from the night shift
      was associated with an increased number of incidents (two wheels outside the lane
      marking, from 2.4 to 7.6 times), decreased time to first accident, increased
      lateral deviation (from 18 to 43 cm), increased eye closure duration (0.102 to
      0.143 s), and increased subjective sleepiness. The results indicate severe
      postnight shift effects on sleepiness and driving performance.

PMID- 15743328
TI  - Effect of the diurnal rhythm and 24 h of sleep deprivation on dichotic temporal
      order judgment.
AB  - The present study examined the impact of mild (24 h) sleep deprivation and of the
      circadian rhythm on auditory temporal resolution, measured by dichotic temporal
      order judgment (TOJ). The rationale for the present study was based on several
      areas of research. First, the 'sleep-based neuropsychological perspective'
      hypothesis posits that sleep reduction initially impacts the functions associated
      with intact prefrontal cortical activity, e.g. language tasks. Secondly, recent
      studies indicate the importance of the role of auditory temporal resolution in
      speech comprehension. Thirdly, there is accumulating evidence of the involvement
      of prefrontal cortical structures in auditory temporal resolution. We
      hypothesized that mild to moderate sleep deprivation would affect dichotic TOJ
      negatively. The results showed that: (1) 24 h of sleep deprivation significantly
      reduced the overall level of accuracy in dichotic TOJ and increased dichotic TOJ
      threshold from 57.61 ms to 73.93 ms, a reduction in temporal resolution of 28.3%;
      (2) dichotic TOJ was subject to a small, but significant diurnal rhythm having a
      nadir in early to mid afternoon. As auditory temporal resolution of speech and
      non-speech sounds seems to be dependent on intact functioning of the left
      inferior and left dorso-lateral prefrontal cortex (PFC), these data strengthen
      the argument that even mild to moderate sleep deprivation can impact negatively
      on PFC-dependent functions. Furthermore, based on these findings, we suggest that
      the deficit in auditory temporal resolution in individuals suffering from sleep
      loss may also affect language comprehension.

PMID- 15743330
TI  - Fatigue-related impairment in the speed, accuracy and variability of psychomotor
      performance: comparison with blood alcohol levels.
AB  - Cognitive performance is impaired by fatigue arising from sustained wakefulness
      and alcohol. Three recent papers directly compared the effects of increasing
      fatigue and blood alcohol concentration (%BAC) to provide a framework for
      understanding fatigue-related cognitive impairment. While the expression of
      fatigue-related cognitive impairments in terms of %BAC equivalents is sound, the
      methodology in each study was flawed in that the statistics used to compare the
      effects of %BAC and fatigue on cognition did not account for variation between or
      within each condition. The point estimates of the difference between a baseline
      and any level of fatigue or %BAC provided no indication of the size of difference
      that could reasonably be expected by chance. Importantly, all studies showed that
      variation increased as cognitive performance declined because of both increasing
      fatigue and %BAC. The current study compared the effect of increasing levels of
      %BAC and fatigue on the simple reaction task from the CogState test battery on 40
      healthy adults using statistical methods that account for intra-individual and
      within-group variability in performance. After 24 h of sustained wakefulness and
      with 0.08%BAC, individuals showed maximal cognitive impairment; however, the
      magnitude of impairment found for fatigue was equivalent only to that observed
      for 0.05%BAC. Re-analysis of the data using percentage change scores indicated
      that the magnitude of fatigue-related cognitive impairment was much greater than
      that detected for 0.08%BAC. This suggests that previous studies that have not
      accounted for variability in the performance data have overestimated the effect
      of fatigue on cognitive performance.

PMID- 15743331
TI  - Comparison of postnatal development of heart rate responses to trigeminal
      stimulation in sleeping preterm and term infants.
AB  - Autonomic dysfunction has been regarded as a possible cause of the sudden infant
      death syndrome (SIDS) and it has been suggested that preterm infants, who are at
      a greater risk of SIDS than term infants, may have immature autonomic control.
      Our aim was to compare the maturation of cardiac autonomic control during sleep
      in preterm and term infants by examining heart rate responses to arousing and non
      arousing trigeminal stimuli. Preterm infants (n = 15) and term infants (n = 24)
      were studied longitudinally with daytime polysomnography. Air-jet stimulation of
      the nares was delivered in both active sleep (AS) and quiet sleep (QS), and heart
      rate (HR) changes recorded for both arousal and non-arousal responses. Changes in
      HR (DeltaHR%) were calculated as the relative differences between baseline HR
      (BHR) and either MaxHR (arousal) or MinHR (non-arousal). Comparisons of HR
      changes between sleep states and postnatal ages were made with two-way anova for
      repeated measures and between groups with two-way anova. The increase in HR
      (DeltaHR%) was greater in term than preterm infants (P < 0.05), but only at 2-3
      weeks corrected postnatal age (CPA). In preterm infants, there were no
      differences in BHR between sleep states, whereas in term infants, BHR was higher
      in AS than in QS at 2-3 weeks and 2-3 months of age. The smaller DeltaHR% to
      arousing stimuli in preterm infants compared with term infants at 2-3 weeks
      suggests that cardiac sympathetic activity in preterm infants may be lower than
      in term infants. This mechanism may account for the increased risk for SIDS of
      preterm infants.

PMID- 15743332
TI  - The scoring of arousals in healthy term infants (between the ages of 1 and 6
      months).
AB  - Various definitions of arousals have been used in infants. An international group
      of experts has worked on a consensus for the scoring of arousals in healthy
      infants, aged between 1 and 6 months. This opinion paper summarizes the consensus
      statement on the scoring of arousal. The paper reviews recommended techniques for
      the recording of arousal in infants. Scoring includes the differentiation between
      subcortical activation, with no visible change n the electroencephalograph (EEG)
      recording, and cortical arousals associated with EEG changes. The arousals are
      further scored as spontaneous or induced, according to environmental conditions.
      Potential limitations to the method are discussed, with the hope that this
      document could contribute to promote further progresses in the scoring of infants
      arousals from sleep.

PMID- 15743333
TI  - CSF iron, ferritin and transferrin levels in restless legs syndrome.
AB  - The aim of this study is evaluating iron, ferritin, and transferrin in both serum
      and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that
      iron deficiency in the central nervous system (CNS) causes the symptoms as a
      result of the dysfunction of dopaminergic systems. These parameters,
      polysomnographic sleep measures, and subjective evaluation of the sleep quality
      were compared in 10 patients of idiopathic RLS (RLS group) and 10 age-matched
      patients of psychophysiological insomnia without RLS symptoms (non-RLS group).
      With sleep patterns, sleep latency was longer and sleep efficiency was lower in
      the RLS group than those in the non-RLS group. Periodic leg movement index in the
      RLS group was higher than that of the non-RLS group. With serum examination,
      there were no significant differences for the iron, ferritin, and transferrin
      values between the both groups. With CSF examination, the iron and ferritin
      values were lower and the transferrin values were higher in the RLS group than
      those in the non-RLS group. There was positive correlation between the serum and
      CSF ferritin levels in the both groups, but the slope of the regression lines for
      the RLS group was lower than that for the non-RLS group. These results indicate
      low brain iron concentration caused by the dysfunction of iron transportation
      from serum to CNS in patients with idiopathic RLS.

PMID- 15743334
TI  - Chronic insomnia and performance in a 24-h constant routine study.
AB  - Insomniacs report daytime functioning problems, but studies of neurobehavioral
      functioning in insomniacs have shown little objective evidence of impairment. In
      addition, very little is known about the influence of the circadian clock on
      performance in chronic insomniacs. In the present study, we investigated whether
      chronic insomnia is associated with an overall performance deficit, and what the
      effect is of circadian rhythmicity, under strictly controlled laboratory
      conditions. A 24-h experiment was carried out under constant routine conditions.
      Psychomotor performance, body temperature, and subjective functioning of 11
      insomniacs and 13 healthy subjects were assessed. The insomniacs showed
      significant overall performance impairments in vigilance, working memory, and
      motor control. In addition, body temperature, performance and subjective
      functioning showed a circadian pattern similar to healthy subjects, with trough
      values in the late night/early morning and peak values in the early evening. Self
      reported functioning among the insomniacs indicated mood disturbances,
      concentration problems, elevated fatigue and elevated sleepiness. The results
      indicated that chronic insomnia is associated with a substantial lowering of the
      24-h level of performance and subjective functioning, irrespective of the type of
      task and/or the particular parameter, and without differential effects of
      circadian rhythmicity. Apparently, chronic insomnia has a negative impact upon
      performance as measured under strictly controlled, unmasked conditions.

PMID- 15743335
TI  - Circadian activity rhythm in demented and non-demented nursing-home residents
      measured by telemetric actigraphy.
AB  - There is a need to develop unobtrusive methods for long-term monitoring of
      sleep/wake and circadian activity patterns in the elderly both in nursing homes
      and at home settings as sleep is important for health and well-being. The IST
      Vivago WristCare is an active social alarm system, which provides continuous
      telemetric monitoring of the user's activity. We examined how the activity signal
      measured by IST Vivago differed between demented and non-demented subjects living
      in a nursing home, and how it correlated with the subjective assessment of sleep
      quality and daytime alertness. The activity signal data together with subjective
      assessments of sleep quality and daytime vigilance were collected from 42
      volunteers (aged 56-97 years; 23 demented and 19 non-demented) for at least 10
      days. The demented subjects had lower daytime activity and higher nocturnal
      activity than the non-demented subjects. Correlations between the activity
      parameters and self-assessments were weak but statistically significant. We also
      found correlation between functional ability and diurnal activity. The results
      are in line with previous studies with demented and non-demented elderly subjects
      and suggest that the IST Vivago system provides a valid instrument for
      unobtrusive continuous long-term monitoring of the circadian rhythm and
      sleep/wake patterns in the elderly.

PMID- 15743336
TI  - Sleep apnea-related cognitive deficits and intelligence: an implication of
      cognitive reserve theory.
AB  - Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are
      well demonstrated, but the pathophysiology of these deficits is still
      controversial, as the relationship between OSA severity and cognitive deficits is
      usually weak. Our study considers the possible relationship between OSA-related
      cognitive deficits and the overall intellectual function of OSA patients. Forty
      seven OSA patients and 36 normal individuals underwent a neuropsychological
      battery test assessing attention and alertness. According to the resulting IQ
      score, patients and controls were divided into a high-intelligence group (IQ > or
      = 90th percentile) and a normal-intelligence group (50 < or = IQ < 90%ile).
      Between the two patient groups there were no significant differences noticed,
      regarding OSA severity or sleepiness. High-intelligence patients showed the same
      attention/alertness performance compared with the high-intelligence controls. On
      the contrary, patients with normal-intelligence showed attention/alertness
      decline compared with the normal-intelligence control group. The two patient
      groups were re-examined with the same battery test after at least 1 year of CPAP
      treatment. At re-examination neither patient group showed any differences
      regarding attention and alertness compared with the control groups. We assume
      that high-intelligence may have a protective effect against OSA-related cognitive
      decline, perhaps due to increased cognitive reserve.

PMID- 15743337
TI  - Sleep disturbance and daytime symptoms in wheezing school-aged children.
AB  - The aim of the study was to investigate whether wheezing is associated with
      disturbed sleep and increased daytime symptoms in school-aged children. A random
      sample of 1234 children, aged 6-14 years, participated in a respiratory health
      study in the region of Antwerp. The International Study of Asthma and Allergies
      in Childhood questionnaire and a separate sleep questionnaire were completed. In
      the children who wheezed in the last 12 months, sleep quality was more frequently
      disturbed due to nocturnal awakenings and restless sleep compared with children
      who did not wheeze. Daytime sleepiness and tiredness were more common in wheezing
      than in non-wheezing children. After adjusting for possible confounders a
      positive association was found between wheeze and: difficulties falling asleep
      [odds ratio (OR) = 2.0], restless sleep (OR = 5.0), daytime sleepiness (OR = 3.8)
      and daytime tiredness (OR = 5.1). Chronic cough (OR = 2.4), snoring (OR = 2.0),
      chronic rhinitis (OR = 2.6) and eczema (OR = 3.3) were associated with disturbed
      sleep. Chronic cough (OR = 2.5) and rhinitis (OR = 4.1) were related to daytime
      tiredness. Chronic rhinitis was an important risk factor for snoring (OR = 1.9).
      In wheezing school-aged children, decreased quality of sleep and increased
      daytime tiredness and sleepiness were more often reported. Upper airway symptoms
      were related to the sleep disturbances.

PMID- 15743338
TI  - Endocrinological and catecholaminergic alterations during sleep deprivation and
      recovery in male rats.
AB  - Since previous data of our group showed increased concentrations in HPA axis
      hormones in sleep deprived rats, we hypothesized that this augmentation could
      produce effects in other hormonal systems, particularly in the sexual system.
      Considering that little is known about how the hormonal system changes during the
      recovery period after sleep deprivation (SD), our objective was to examine from
      what point SD alters sexual and stress-related hormones along with plasma
      catecholamine concentrations during 4 days. We also sought to verify the time
      course of their recovery after an equivalent period of recovery sleep. Rats were
      deprived of sleep by the platform technique for 1-4 days and were allowed to
      recover for the same period. Plasma catecholamines [dopamine (DA) and
      noradrenaline (NOR)], testosterone, estrone, progesterone, prolactin,
      corticosterone and adrenocorticotropic hormone (ACTH) concentrations were
      measured. Comparisons between groups showed that the SD procedure used in the
      present study produced marked alterations in almost all studied hormones from 24
      h of SD, except for estrone and prolactin (which required 96 h of SD to become
      altered). Testosterone and estrone decreased, whereas progesterone, prolactin,
      corticosterone, ACTH, DA and NOR increased. During recovery period, progesterone,
      prolactin and corticosterone concentrations returned to control levels, whereas
      testosterone, estrone, NOR and DA did not. In addition, after 48 h of recovery
      ACTH and NOR decreased below control concentrations, remaining low until 96 h of
      sleep recovery. Thus, SD showed long lasting, differential effects upon these
      neurochemicals suggesting that each has its own pattern of responses to SD as
      well as variable periods of recovery.

PMID- 15743340
TI  - Unresolved issues in sleep ontogeny: a response to Blumberg et al.

PMID- 15743339
TI  - The ontogeny of mammalian sleep: a response to Frank and Heller (2003).
AB  - In a recent review, Frank and Heller (2003) provided support for their 'presleep
      theory' of sleep development. According to this theory, rapid eye movement (REM)
      and non-rapid eye movement (Non-REM) sleep in rats emerge from a common
      'dissociated' state only when the neocortical EEG differentiates at 12 days of
      age (P12). Among the assumptions and inferences associated with this theory is
      that sleep before EEG differentiation is only 'sleep-like' and can only be
      characterized using behavioral measures; that the neural mechanisms governing
      presleep are distinct from those governing REM and Non-REM sleep; and that the
      presleep theory is the only theory that can account for developmental periods
      when REM and Non-REM sleep components appear to overlap. Evidence from our
      laboratory and others, however, refutes or casts doubt on these and other
      assertions. For example, infant sleep in rats is not 'sleep-like' in that it
      satisfies nearly every criterion used to characterize sleep across species. In
      addition, beginning as early as P2 in rats, myoclonic twitching occurs only
      against a background of muscle atonia, indicating that infant sleep is not
      dissociated and that electrographic measures are available for sleep
      characterization. Finally, improved techniques are leading to new insights
      concerning the neural substrates of sleep during early infancy. Thus, while many
      important developmental questions remain, the presleep theory, at least in its
      present form, does not accurately reflect the phenomenology of infant sleep.

PMID- 15743343
TI  - Three challenges: propofol, colonoscopy by undertrained physicians, and CT
      colonography.

PMID- 15743345
TI  - Colorectal cancer in African Americans.
AB  - Colorectal cancer in African Americans has an increased incidence and mortality
      relative to Whites. The mean age of CRC development in African Americans is
      younger than that of Whites. There is also evidence for a more proximal colonic
      distribution of cancers and adenomas in African Americans. African Americans are
      less likely to have undergone diagnostic testing and screening for colorectal
      cancer. Special efforts are needed to improve colorectal cancer screening
      participation rates in African Americans. Clinical gastroenterologists should
      play an active role in educating the public and primary care physicians about
      special issues surrounding colorectal cancer in African Americans. Community
      healthcare groups and gastrointestinal specialists should develop culturally
      sensitive health education programs for African Americans regarding colorectal
      cancer. The high incidence and younger age at presentation of colorectal cancer
      in African Americans warrant initiation of colorectal cancer screening at the age
      45 yr rather than 50 yr.

PMID- 15743346
TI  - Patient-derived health state utilities for gastroesophageal reflux disease.
AB  - BACKGROUND AND AIMS: Gastroesophageal reflux disease is a chronic disease that
      adversely affects health-related quality of life. The purpose of this study was
      to derive health state utilities for patients with chronic heartburn symptoms.
      METHODS: We used a custom-designed computer program in order to elicit utilities
      with the time-tradeoff and standard-gamble techniques. Patients with chronic
      (more than 6 months) symptoms of gastroesophageal reflux disease entered the
      study. Two interviews were performed in random sequence either initially on
      medications for heartburn that adequately controlled symptoms, or off of
      medications for 1 wk while the patient was symptomatic. We also collected data
      using visual-analog scales, quality of life in reflux and dyspepsia (QOLRAD), and
      Gastrointestinal Symptom Rating Scale (GSRS) scores. RESULTS: We invited 222
      patients to participate; 158 (71%) patients (129 men, 29 women) completed the
      study. Barrett's esophagus was present in 40 (25%), erosive disease in 17 (11%),
      and 118 (74%) had comorbid conditions. The mean (+/-SD) utility ratings were 0.94
      +/- 0.09 on medical therapy and 0.90 +/- 0.12 off medications for patients with
      reflux alone using time tradeoff (p= 0.004), and 0.94 +/- 8.0 both on and off of
      antireflux medications with standard-gamble assessment (p= 0.96). Mean time
      tradeoff scores were also significantly lower off of medications for patients
      with other comorbid conditions (p= 0.002). There was no significant difference
      between mean utility scores for patients with or without Barrett's esophagus or
      erosive disease. CONCLUSION: Gastroesophageal reflux disease adversely affects
      health-related quality of life. Time-tradeoff utility for patients with reflux
      disease is substantially higher when patients are on medication than off
      medications.

PMID- 15743347
TI  - Gambling with gastroesophageal reflux disease: should we worry about the QALY?
AB  - Gastroenterologists mainly deal with chronic organic and functional illnesses
      that are not life threatening but can be expensive to treat. How this compares
      with the management of other diseases that cause significant mortality is an
      important question to answer if health-care resources are to be allocated
      appropriately. Comparing health care in terms of cost per quality adjusted life
      year (QALY) gained is one approach to this problem although there are concerns
      about whose values should be elicited and how QALYs are measured.

PMID- 15743348
TI  - Reversibility of GERD ultrastructural alterations and relief of symptoms after
      omeprazole treatment.
AB  - BACKGROUND: Dilation of intercellular spaces (DIS) of human esophageal
      epithelium, evident at transmission electron microscopy (TEM), is an early marker
      of damage caused by gastroesophageal reflux, but its reversibility after therapy
      has not been investigated. AIM: To evaluate whether omeprazole can induce the
      healing of DIS. METHODS: Thirty-eight symptomatic patients, 22 with nonerosive
      reflux disease (NERD) and 16 with erosive esophagitis (EE), classified on the
      basis of 24-h pH monitoring, were enrolled. During upper gastrointestinal
      endoscopy, six biopsies from apparently normal mucosa were taken within the lower
      5 cm of the esophagus for histological and TEM analysis. One hundred computer
      measurements were taken on TEM photomicrographs of the specimens in each patient.
      After 3 months of omeprazole 40 mg/die a further endoscopy with biopsies was
      performed. In patients with persistent heartburn and/or incomplete
      ultrastructural recovery of esophageal epithelium, a new endoscopy was performed
      after 3 more months of treatment. RESULTS: After 3 months of therapy, 35 patients
      (92.1%) showed a complete recovery of DIS and resolution of heartburn. Three
      patients required 3 more months of therapy because of an incomplete recovery of
      the epithelium correlated with sporadic heartburn. Healing of the mucosa was
      achieved in two patients, whereas one had an incomplete recovery of DIS with
      persistent heartburn. CONCLUSIONS: Three and six months of omeprazole therapy led
      to a complete recovery of DIS in 92.1% and 97.4% of cases, respectively. No
      significant differences of DIS between NERD and EE were noted. Complete recovery
      of DIS was accompanied by regression of heartburn in all cases.

PMID- 15743349
TI  - Dilated intercellular spaces of esophageal epithelium in nonerosive reflux
      disease patients with physiological esophageal acid exposure.
AB  - OBJECTIVES: It has been demonstrated that dilation of intercellular spaces of
      esophageal epithelium is a marker of tissue injury in GERD patients with a
      pathological esophageal acid exposure time. To evaluate the relationship among
      ultrastructural changes, acid esophageal exposure, and GERD symptoms,
      intercellular space diameters have been assessed in nonerosive reflux disease
      (NERD) patients with/without abnormal acid exposure time. METHODS: Following a
      pharmacological wash-out, 20 NERD patients underwent upper endoscopy, esophageal
      manometry, and 24-h pH monitoring. Biopsies were taken at 5 cm above the lower
      esophageal sphincter and intercellular space diameters were measured on
      transmission electron microscopy photomicrographs. Seven asymptomatic controls
      underwent the same protocol. RESULTS: Acid exposure time was in the normal range
      in all controls and in 11 patients (NERD pH-negative); it was abnormal in 9
      patients (NERD pH-positive). Mean intercellular space diameter in NERD pH
      negative and in NERD pH-positive patients was three times greater than in
      controls (1.45 and 1.49 microm vs 0.45, p < 0.001). Mean values of maximum
      intercellular spaces in all NERD patients were greater, two-fold or more, than
      those in controls (p < 0.001). No difference in mean and maximal space diameters
      was observed between NERD pH-positive and pH-negative patients. CONCLUSIONS:
      Dilation of intercellular spaces is a feature of NERD patients, irrespective of
      esophageal acid exposure, and can be considered an objective, structural marker
      of GERD symptoms. Impaired esophageal mucosal resistance, even to small amounts
      of acid refluxate, plays a key role in the pathophysiology of NERD.

PMID- 15743350
TI  - Dilated intercellular spaces: extending the reach of the endoscope.
AB  - Two manuscripts in this issue utilize quantitative methods to analyze the
      association between gastroesophageal reflux disease (GERD) and dilated
      intercellular spaces (DIS) evident on transmission electron microscopy of the
      esophageal epithelium. One study of 20 patients found that, irrespective of
      whether or not a pH study was positive, all GERD patients who had responded to
      proton pump inhibitors therapy had intercellular space measurements that were at
      least twice normal. The other study demonstrated that DIS resolved with effective
      GERD therapy in essentially every instance. Both studies suggest that DIS are an
      objective structural marker of endoscopy-negative reflux disease.

PMID- 15743352
TI  - Barrett's esophagus in females: a comparative analysis of risk factors in females
      and males.
AB  - OBJECTIVES: Gastroesophageal reflux symptoms occur with similar frequency in
      males and females, yet Barrett's esophagus is less common in females. The reason
      for this disparity is unknown. The aim of this study was to determine the factors
      related to Barrett's in females. METHODS: The records of 796 patients (462 male,
      334 female) evaluated from 1990 to 2000 for symptoms of reflux were
      retrospectively reviewed. Physiologic abnormalities based on results of
      endoscopic, motility, pH, and Bilitec testing were identified, and factors
      related to the presence of Barrett's were determined using univariate and
      multivariate analysis. RESULTS: Females with reflux symptoms were significantly
      less likely to have a positive 24-h pH test, a defective lower esophageal
      sphincter, or a hiatal hernia than males with reflux symptoms. Further, females
      with reflux on the basis of an abnormal 24-h pH test had significantly less
      esophageal acid exposure than males with reflux. In contrast, esophageal exposure
      to refluxed acid and bilirubin was similar in females (n = 50) and males (n =
      136) with Barrett's. On multivariable analysis increased esophageal bilirubin
      exposure was the only significant factor associated with the presence of
      Barrett's in male and female patients with reflux disease. CONCLUSIONS: Females
      with reflux symptoms have less esophageal acid exposure on average than males.
      However, females and males with Barrett's have a similar severity of reflux, and
      the female gender does not protect against the development of Barrett's in the
      setting of advanced reflux disease. Esophageal bilirubin exposure is the major
      risk factor for the presence of Barrett's in patients with reflux disease.

PMID- 15743351
TI  - Differences in ERK activation in squamous mucosa in patients who have
      gastroesophageal reflux disease with and without Barrett's esophagus.
AB  - OBJECTIVES: In some patients with gastroesophageal reflux disease (GERD), the
      reflux-damaged esophageal squamous epithelium heals through the process of
      intestinal metaplasia (resulting in Barrett's esophagus) rather than through the
      regeneration of more squamous cells. We hypothesized that squamous epithelium in
      Barrett's esophagus might have abnormalities in activation of the extracellular
      regulated kinases 1 and 2 (ERK1/2) signaling pathway that may facilitate
      esophageal repair through metaplasia in response to acid-induced injury. METHODS:
      Endoscopic biopsies were taken from distal esophageal squamous mucosa in patients
      who had GERD with and without Barrett's esophagus and in controls, before and
      after esophageal perfusion with 0.1 N HCl acid. Basal ERK1/2 phosphorylation,
      acid-induced ERK1/2 activity and phosphorylation, and localization of
      phosphorylated ERK1/2 were determined using immunoblotting, Western blotting, and
      immunohistochemistry. RESULTS: Compared to patients with Barrett's esophagus,
      patients with GERD exhibited significantly lower baseline levels of
      phosphorylated ERK1/2 expression (35 +/- 4%vs 90 +/- 21% control, p= 0.01) Acid
      exposure significantly increased ERK1/2 activity (346.6 +/- 51.90 to 446.8 +/-
      62.44 RIU, p= 0.02) and phosphorylation (3.55 +/- 1.26 to 4.49 +/- 1.25 [ratio
      phospho/total ERK], p= 0.01) in the squamous mucosa of GERD patients, but not in
      those with Barrett's esophagus or in controls. CONCLUSIONS: Between patients with
      Barrett's esophagus and patients with uncomplicated GERD, there are significant
      differences in baseline levels and in acid-induced activation of ERK1/2 in
      esophageal squamous epithelium. To our knowledge, this is the first description
      of a molecular, phenotypic feature that distinguishes the esophageal squamous
      mucosa of GERD patients with and without Barrett's esophagus.

PMID- 15743353
TI  - Age and sex distribution of the prevalence of Barrett's esophagus found in a
      primary referral endoscopy center.
AB  - BACKGROUND: Both the demographics underlying the sex ratio in the prevalence of
      Barrett's esophagus (BE) and the status of BE without intestinal metaplasia (IM)
      are unclear. AIMS: To establish the demographics of histologically proven BE, IM+
      and IM-, over a 15-yr period from a primary referral, endoscopy unit. PATIENTS
      AND METHODS: For all BE patients aged 20-89 yr, identified between 1982 and 1996,
      IM+ or IM-, prevalences were calculated per 100 first endoscopies. RESULTS: A
      total of 492 cases of BE, 320 (248 IM+) in males, 175 (127 IM+) in females were
      identified in 21,899 first endoscopies (10,939 males, 10,960 females). Between
      ages 20 and 59 yr in males and 20-79 in females, IM+, IM- and all BE prevalences
      rose by +/-7.36% for each additional year of age (p= 0.92) with, however, a 20-yr
      age shift between the sexes, resulting in a male:female OR 4.15 95% CI 2.99-5.77.
      A declining rate of increase in over 59 males resulted in an overall male:female
      OR 2.14, 95% CI 1.77-2.58. Over the age of 79 yr, BE prevalences/100 first
      endoscopies fell from a maximum of 5.1 in males and 3.65 in females to 3.38 and
      2.53, respectively. CONCLUSION: The 4:1 sex ratio and 20-yr age shift between
      males and females in the prevalence of BE, both IM+ and IM-, found in younger age
      groups, was the main cause of the overall BE 2:1 sex ratio. The very similar
      demographics of IM- and IM+ BE suggest they may be two consecutive stages in the
      same metaplastic process.

PMID- 15743354
TI  - Effect of a new diagnosis of Barrett's esophagus on insurance status.
AB  - BACKGROUND: Barrett's esophagus (BE) is associated with an increased risk of
      adenocarcinoma of the esophagus. Despite this increased risk, most cohort studies
      demonstrate that the mean life expectancy of subjects with BE is no different
      than age-matched controls. The indirect costs associated with a diagnosis of BE
      are unclear. AIM: To assess the effect of a diagnosis of BE on insurance
      premiums. METHODS: We assessed twenty national life insurance companies (10 in
      southern California, 10 in North Carolina) to determine the effect of a diagnosis
      of BE on life insurance premiums. Our base case in Los Angeles was a 36-yr-old
      female nonsmoker, and in North Carolina, a 43-yr-old Caucasian male nonsmoker,
      both in excellent health except for a diagnosis of prevalent BE with no
      dysplasia. The policy requested was a 20-yr guaranteed term life insurance in the
      amount of $1,000,000. Companies were asked for their best price exclusive of the
      BE, and also their best price when considering BE as a preexisting condition. For
      those companies not offering the "preferred" rates, the insurance representative
      was subsequently sent a physician's letter explaining BE and providing data
      substantiating a normal life expectancy in the condition. Companies were also
      asked for health insurance quotes, including premiums and deductibles, inclusive
      and exclusive of the diagnosis of BE. RESULTS: Twenty national insurance
      companies were contacted. For the 43-yr-old man with no BE, the yearly
      "preferred" premium for life insurance averaged $1,255. The mean cost of the
      policies offered to the same individual with BE as a preexisting condition was
      $2,731 (p < 0.001). For the 36-yr-old female the base rate exclusive of BE was
      $517, with a range of $472-$551. After inclusion of the diagnosis of BE, the mean
      rate rose by 177%, to $1,434, with a range of $1,144-$1,896. Companies either
      refused to provide health insurance to the individual with BE or would not
      provide a quote without review of the medical record. None of the insurance
      companies changed their quoted rates after receiving the letter written by the
      physician on behalf of the individual. CONCLUSIONS: Despite the preponderance of
      data demonstrating a normal life expectancy associated with the condition, a
      diagnosis of BE more than doubles life insurance premiums, and impacts the
      availability of health insurance. Further steps to educate insurance companies
      about the risks associated with BE are warranted, and patients should understand
      this additional "risk" of endoscopic screening for BE. There are significant
      indirect costs associated with a diagnosis of BE.

PMID- 15743355
TI  - Evidence that loss of sonic hedgehog is an indicator of Helicobater pylori
      induced atrophic gastritis progressing to gastric cancer.
AB  - BACKGROUND: The absence of sonic hedgehog (Shh) correlates with the development
      of intestinal metaplasia (IM) suggesting the possibility of an association
      between Shh expression and neoplastic transformation. AIM: To examine Shh
      expression in the noncancerous mucosa of patients with gastric cancer and compare
      it to Shh expression in Helicobater pylori-infected and uninfected controls. We
      also assessed the relationship between the type of IM and Shh expression.
      METHODS: Fifty-three patients with endoscopic mucosal resection (EMR) for early
      gastric cancer and 48 sex- and age-matched controls were studied. Two specimens
      each were obtained from the greater and lesser curves of the corpus and from the
      greater curve of the antrum. The histopathological grading used was the updated
      Sydney System. IM was categorized by staining with Alcian blue/high iron diamine.
      Expression of Shh was evaluated by immunostaining. RESULTS: The Shh
      immunostaining in the corpus lesser curve significantly correlated with the
      scores of atrophy and IM. Shh staining in the antrum was significantly higher in
      H. pylori-negative controls than those in H. pylori-positive controls as well as
      in patients without IM compared to those with IM (p < 0.001). The Shh staining in
      the corpus lesser curve decreased in H. pylori-negative controls, -positive
      controls and the cancer group respectively (p= 0.003), and was significantly
      higher (p= 0.006) in the complete IM group compared to those in the incomplete IM
      group. CONCLUSIONS: Loss of Shh is an early change that occurs in the mucosa
      prior to neoplastic transformation. Its loss correlates with the type of IM and
      may play a role in carcinogenesis.

PMID- 15743356
TI  - Helicobacter pylori infection: a protective factor for esophageal squamous cell
      carcinoma in a Taiwanese population.
AB  - AIM: Many researchers have reported the inverse relationship between Helicobacter
      pylori (H. pylori) infection and esophageal adenocarcinoma risk, but very few
      studies have examined the association between H. pylori infection and the
      development of esophageal squamous-cell carcinoma (ESCC). Therefore, the aim of
      this study is to evaluate the relationship between H. pylori infection and ESCC
      risk. METHOD: Subjects were cancer cases, pathologically proven to have ESCC, in
      two large medical centers in Kaohsiung metropolitan of southern Taiwan between
      August 2000 and May 2003. Controls were from the healthy subjects who lived in
      Kaohsiung metropolitan and voluntarily participated in one large multiyear of
      gene-environmental study. In total, 127 cases (116 males and 11 females) and 171
      controls (161 males and 10 females) were recruited in the same period of time for
      interviews. H. pylori seropositivity was determined by an enzyme-linked
      immunosorbant assay measuring IgG. RESULTS: A total of 28 (22.1%) and 74 (43.3%)
      out of 127 cases and 171 controls, respectively, had positive H. pylori
      infection. After adjusting for other covariates, subjects with positive H. pylori
      infections had a significantly reduced risk (adjusted odds ratio (AOR) = 0.51;
      95% CI = 0.27-0.96; p= 0.037) of developing ESCC than those without. This result
      was even more pronounced in the groups of younger subjects, nonsmokers, or
      nondrinkers. In addition, among the 117 cancer patients who provided information
      about site of cancer lesion, the present study found that subjects with cancer
      lesions in the lower third of the esophagus had significantly fewer positive H.
      pylori infections (AOR = 0.34; 95% CI = 0.14-0.80; p= 0.013) than controls.
      CONCLUSION: Our findings suggest that H. pylori infection may protect against the
      development of ESCC. Additional studies are needed to confirm these findings.

PMID- 15743357
TI  - Endosonographic and histopathological staging of extrahepatic bile duct cancer:
      time to leave the present TNM-classification?
AB  - OBJECTIVES: The discrepancy between high rates of sensitivity, specificity, and
      accuracy for intraductal ultrasonography (IDUS) in extrahepatic bile duct
      carcinoma and the failure to depict different wall layers as defined by the TNM
      classification have not yet been elucidated sufficiently. METHODS: In a
      prospective study, endosonographic images were correlated with histomorphology
      including immunohistochemistry. Using IDUS, we examined fresh resection specimens
      of patients who had undergone pancreato-duodenectomy. For histological analysis,
      the formalin-fixed and paraffin-embedded specimens were stained by hematoxylin
      eosin, elastica-van-Gieson, and immunohistochemically by smooth muscle-actin. To
      confirm our hypothesis, further cases from the archives were analyzed
      histopathologically and immunohistochemically. RESULTS: The various wall layers
      of the extrahepatic bile duct as described by the International Union Against
      Cancer are neither histomorphologically nor immunohistochemically consistently
      demonstrable. Especially, a clear differentiation between tumor invasion beyond
      the wall of the bile duct (T2) and invasion of the pancreas (T3) by
      histopathological means is often not possible. Endosonographic images using high
      resolution miniprobes similarly confirm the difficulty in imaging various layers
      in the bile duct wall. CONCLUSIONS: Most adaptations made by the sixth edition of
      the TNM classification accommodate to the endosonographic and most of the
      histopathological findings as demonstrated in our study. In contrast to the new
      edition, however, our findings suggest to combine T2- and T3-staged tumors into
      one single class leading to clarification, and improved reproducibility of
      histopathological staging.

PMID- 15743358
TI  - Endoscopic ultrasound errors in esophageal cancer.
AB  - BACKGROUND: Previous assessments of endoscopic ultrasound (EUS) classification of
      esophageal cancer are dominated by symptomatic patients with advanced stage
      disease. Fewer data exist on EUS errors in a cohort balanced between early and
      advanced disease. PURPOSE: Assess EUS errors in classification of esophageal
      cancer in a more balanced cohort, and identify clinical and tumor characteristics
      associated with EUS errors. METHODS: A total of 266 patients underwent EUS and
      esophagectomy without preoperative chemoradiotherapy. Pathologic classification
      of disease extent: 108 (41%) tumors were confined to the esophageal wall (pTis
      pT2, pN0, pM0); 158 (59%) were advanced beyond (pT3-pT4, pN1, or pM1). Logistic
      regression analysis was performed to identify correlates of error in T
      classification and disease extent using 10 clinical and tumor characteristics
      (gender, age, dysphagia, weight loss, tumor length, location, traversability,
      morphology, histopathologic type, and histologic grade). RESULTS: EUS erroneously
      predicted pathologic T (pT) in 119 patients (45%). When T classification was
      dichotomized into tumors whose depth of invasion was not beyond the muscularis
      propria (pTis-pT2) and those beyond (pT3-pT4), errors occurred in 42 patients
      (16%). EUS erroneously predicted N classification in 67 patients (25%), and was
      insensitive to the presence of distant metastases. EUS misclassified disease
      extent in 40 patients (15%). Logistic regression analysis indicated that weight
      loss and tumor length were the only clinical and tumor characteristics correlated
      with EUS errors; more weight loss was associated with decreased odds of
      misclassification, while the odds of misclassification were four to six times
      greater for intermediate length tumors than for shorter tumors. CONCLUSIONS: EUS
      errors, particularly in predicting pT, are more frequent than previously
      reported. Weight loss and tumor length are the only clinical and tumor
      characteristics correlated with EUS errors.

PMID- 15743359
TI  - Cost effectiveness of testing strategies for chronic hepatitis C.
AB  - OBJECTIVE: This paper compares nine strategies for determining hepatitis C
      antibody and viral status. They combine two tests for antibodies (enzyme
      immunoassays (EIA), recombinant immunoblot assays (RIBA)) and one for viremia
      (reverse transcription polymerase chain reaction (PCR)). Using optical density to
      divide EIA results into three categories (high positive, low positive, negative)
      was also considered. METHODS: Decision analysis compared strategies on cost as
      well as sensitivity and specificity with regard to antibody and viral status.
      Parameters in the decision tree included antibody prevalence, proportion viremic,
      sensitivity, specificity, and cost of individual tests. RESULTS: The two best
      strategies are EIA followed by PCR (EIA-->PCR); and EIA with three levels of
      optical density (EIA-OD), followed by RIBA for EIA-OD low positives, and then PCR
      for all positives (EIA-OD-->RIBA-->PCR). EIA-->PCR has equal viral sensitivity,
      slightly lower cost, slightly higher antibody sensitivity, but lower antibody
      specificity compared to EIA-OD-->RIBA-->PCR. The cost per false antibody positive
      avoided using EIA-OD-->RIBA-->PCR rather than EIA-->PCR is $36 when prevalence is
      5%, and $193 when prevalence is 50%. Using EIA-OD-->RIBA-->PCR rather than EIA-
      >PCR results in 112 false antibody positives avoided for every true antibody
      positive missed when prevalence is 5%; this ratio is 18:1 when prevalence is 25%;
      and 6:1 when prevalence is 50%. CONCLUSIONS: EIA-OD-->RIBA-->PCR is the best
      choice when prevalence in the tested group is below 20%. As prevalence increases,
      the choice of EIA-OD-->RIBA-->PCR versus EIA-->PCR will depend on the relative
      importance of avoiding false antibody positives versus missing true antibody
      positives. Our analysis makes explicit the magnitude of this trade-off.

PMID- 15743360
TI  - Identification of chronic hepatitis B patients without significant liver fibrosis
      by a simple noninvasive predictive model.
AB  - OBJECTIVE: Histological assessment of liver fibrosis is important in the
      management of chronic hepatitis B (CHB) infection but poorly accepted by patients
      because of its invasiveness. The aim of this study was to develop a noninvasive
      model to assess liver fibrosis in CHB patients using clinical and routine
      laboratory data. PATIENTS AND METHODS: This was a retrospective study on 235
      treatment-naive viremic CHB patients. Univariate analysis of data from the
      training cohort (n = 150) followed by multivariate logistic regression were
      performed to identify independent predictors of significant fibrosis and generate
      predictive models. The models were validated with the remaining patients or
      validation cohort (n = 85) and by receiver operating characteristics (ROC)
      analysis. RESULTS: Body mass index (BMI), platelet count, serum albumin, and
      total bilirubin levels were identified as independent predictors of bridging
      fibrosis or cirrhosis (Ishak stage 3-6). ROC analysis was performed using the
      predictive probabilities derived from the regression models. The area under the
      ROC curve of the best model was 0.803 (95% CI: 0.729-0.878) for the training
      cohort, 0.765 (95% CI: 0.644-0.885) for the validation cohort, and 0.791 (95% CI:
      0.728-0.854) for the entire cohort. Using the low cut-off probability of 0.15,
      significant fibrosis could be excluded in 83 patients of the total patient
      population (negative predictive value 0.92). CONCLUSIONS: Our noninvasive model
      comprising BMI and three routine laboratory tests was accurate in predicting
      absence of significant fibrosis. Application of this model could provide useful
      additional information on the stage of disease, guide future management
      decisions, and potentially decrease the need for liver biopsy in some CHB
      patients.

PMID- 15743361
TI  - Hemodynamic effects of terlipressin and high somatostatin dose during acute
      variceal bleeding in nonresponders to the usual somatostatin dose.
AB  - OBJECTIVES: High dose of somatostatin infusion achieves a greater reduction of
      hepatic venous pressure gradient (HVPG) than the usual dose, and terlipressin
      decreases HVPG through mechanisms other than somatostatin. Our aim was to assess
      the hemodynamic effects of terlipressin and high somatostatin dose during acute
      variceal bleeding in nonresponders to the usual somatostatin dose. METHODS:
      Hemodynamic studies were performed in 80 patients with cirrhosis and variceal
      bleeding during the first 3 days of admission. After baseline measurements,
      somatostatin was administered (250 microg/h with an initial bolus of 250 microg).
      Patients were considered responders when the HVPG decreased by >10% from baseline
      (n = 31). Nonresponders were randomized under double-blind conditions to a
      control group (n = 7), or to receive terlipressin (2 mg IV bolus, n = 22), or
      high dose of somatostatin (500 microg/h, n = 20). Final measurements were
      obtained 30 min later. RESULTS: Terlipressin caused a decrease in HVPG (from 22.2
      +/- 5 to 19.1 +/- 5.2, p < 0.01) and heart rate (p < 0.01), while mean arterial
      pressure increased (p < 0.01). High somatostatin dose also reduced HVPG (from
      21.8 +/- 3.4 to 19.6 +/- 3.1, p < 0.01), although this decrease was more
      pronounced with terlipressin (15%+/- 9%vs 10%+/- 6% from baseline, p= 0.05). Both
      terlipressin and high somatostatin dose achieved a significantly higher rate of
      response than that in the control group. A decrease in HVPG >20% was observed in
      36% of cases with terlipressin versus 5% with high somatostatin dose (p= 0.02).
      CONCLUSIONS: In nonresponders to usual somatostatin dose, both terlipressin and
      high-dose of somatostatin infusion significantly decreased HVPG and increased the
      rate of hemodynamic responders. Such effects were greater with terlipressin. Both
      treatments may be an alternative when standard somatostatin fails.

PMID- 15743362
TI  - Acute hemodynamic effects of octreotide and terlipressin in patients with
      cirrhosis: a randomized comparison.
AB  - BACKGROUND: Octreotide and terlipressin are widely used in acute variceal
      hemorrhage to reduce the bleeding rate. They purportedly act by mesenteric
      arterial vasoconstriction, thus reducing portal venous flow (PVF) and portal
      pressure. Little is known about the immediate-early hemodynamic effects of these
      drugs. AIM: To compare the acute hemodynamic effects of octreotide and
      terlipressin in patients with cirrhosis. PATIENTS: Forty-two cirrhotic patients
      with a history of variceal bleeding were randomized to receive either octreotide
      100 microg intravenous bolus followed by a continuous infusion at 250 microg/h (n
      = 21), or terlipressin 2 mg intravenous bolus (n = 21). METHODS: Mean arterial
      pressure (MAP), heart rate (HR), hepatic venous pressure gradient (HVPG), and
      PVF, assessed by duplex Doppler ultrasonography, were measured before and at 1,
      5, 10, 15, 20, and 25 min after the start of drug administration. RESULTS:
      Octreotide markedly decreased HVPG (-44.5 +/- 17.8%) and PVF (-30.6 +/- 13.6%)
      compared to the baseline at 1 min (p < 0.05). Thereafter, both variables rapidly
      returned toward the baseline, and by 5 min, no significant differences in HVPG (
      7.1 +/- 28.9%) and PVF (10.2 +/- 26.2%) were noted. A similar transient effect on
      MAP and HR was observed. Terlipressin significantly decreased HVPG (-18.3 +/-
      11.9%) and PVF (-32.6 +/- 10.5%) at 1 min (p < 0.05) and sustained these effects
      at all time points. The effects on arterial pressure and HR were also sustained.
      CONCLUSIONS: Octreotide only transiently reduced portal pressure and flow,
      whereas the effects of terlipressin were sustained. These results suggest that
      terlipressin may have more sustained hemodynamic effects in patients with
      bleeding varices.

PMID- 15743363
TI  - A1166C angiotensin II type 1 receptor gene polymorphism may predict hemodynamic
      response to losartan in patients with cirrhosis and portal hypertension.
AB  - OBJECTIVE: Losartan, a dose of 25 mg/day, has been found to be effective in 50%
      of patients with portal hypertension without adverse effects. We evaluated the
      relationship between genetic polymorphisms of the renin-angiotensin system
      (A1166C angiotensin II type 1 receptor (AT1R), angiotensinogen T174M and M235T,
      and angiotensin-converting enzyme I/D) and the effects of losartan on portal and
      systemic hemodynamic in patients with cirrhosis and portal hypertension. METHODS:
      We performed a longitudinal study that included 23 consecutive patients with
      cirrhosis and esophageal varices who received 25 mg/day of losartan during 12 wk.
      Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured at
      baseline and after treatment. Genomic DNA was extracted from peripheral blood
      leukocytes; genetic polymorphisms of the renin-angiotensin system were
      investigated by polymerase chain reaction and restriction fragment length
      polymorphisms. RESULTS: The homozygous patients for AT1R A allele showed higher
      pulmonary-wedged and free hepatic venous pressure on baseline. After treatment,
      they showed a higher decrease of HVPG (32.5%+/- 19.2) in comparison with patients
      with AC/CC genotype (2.4%+/-18.9), p < 0.01. Ten of 15 patients with AA genotype
      were responders, while only one of eight with AC/CC genotype (p < 0.002);
      genotype AA showed a positive predictive value of 66.6% and negative predictive
      value of 87.5%. CONCLUSIONS: These results suggest that there is a relationship
      between the AT1R A1166C polymorphisms and the therapeutic response to losartan.
      The genetic testing may be used as a predictive factor of this response.

PMID- 15743364
TI  - Estimation of utilities for chronic hepatitis C from SF-36 scores.
AB  - OBJECTIVES: Utilities are the recommended health-related quality of life (HRQOL)
      measure for cost-effectiveness studies. The aim of this study was to estimate
      utilities for chronic hepatitis C health states from published studies reporting
      Short Form-36 (SF-36) quality-of-life scores. METHODS: A systematic review of
      published studies was undertaken. Articles were eligible for review if direct
      HRQOL assessment using the SF-36 in a chronic hepatitis C population was
      reported. SF-36 data were grouped according to hepatitis C virus (HCV) treatment
      status at baseline, stage of liver disease, association with comorbidity, and HCV
      treatment response. The SF-36 scores were then transformed into utilities using
      three different methods. RESULTS: Using Nichol's method, the estimated SF-36 mean
      utilities were 0.87 for sustained virological response (SVR) to interferon-based
      treatment, 0.82 for untreated chronic hepatitis C, 0.81 for precirrhosis, 0.76
      for compensated cirrhosis, 0.69 for decompensated cirrhosis, 0.67 for
      hepatocellular carcinoma (HCC), and 0.77 for liver transplant. Other methods
      showed differences across comparison groups (e.g., treated vs untreated) but
      absolute scores differed substantially by translation method. SF-36 utilities for
      different stages of liver disease varied considerably from expert estimates but
      comparable to direct patient-elicited utilities. CONCLUSIONS: Application of SF
      36 translation methods facilitate use of large existing datasets to generate
      community-weighted utilities for cost-effectiveness analyses, an important
      consideration in the absence of large studies of direct patient-elicited
      utilities in chronic hepatitis C.

PMID- 15743365
TI  - Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable
      bowel syndrome: a pharmacodynamic and pharmacogenomic study.
AB  - BACKGROUND: Cholecystokinin (CCK) is involved in gastrointestinal motor response
      to meals. The potential role of CCK receptor antagonists in functional
      gastrointestinal disorders is unclear. AIMS: To evaluate the effects of
      dexloxiglumide, a CCK-1 receptor antagonist, on gastrointestinal transit (GIT)
      and symptoms in patients with constipation-predominant IBS (C-IBS); and to
      explore the influence of CCK-1 receptor polymorphisms on gut transit and the
      pharmacodynamic response to therapy. METHODS: A total of 36 patients with C-IBS
      and normal to slow baseline colonic transit (CT) were randomized (double-blind,
      parallel design) to 7 days of dexloxiglumide 200 mg or placebo t.i.d. Daily bowel
      habits diaries and weekly relief of IBS symptoms were recorded. At the end of
      treatment, GIT and CT were measured. Peripheral blood DNA was examined for
      polymorphisms in genes controlling CCK: four related to CCK-1, one to the CCK
      gene promoter, and one related to CCK-2. The distributions of allelic variants
      and association with gastric emptying in response to dexloxiglumide and placebo
      were assessed. RESULTS: Dexloxiglumide was associated with accelerated gastric
      emptying t(1/2) (p= 0.004), and slower ascending colon emptying t(1/2) (p <
      0.01), with no significant effect on overall CT or satisfactory relief of IBS.
      There was an association between CCK 779T > C polymorphism and slower rate of
      gastric emptying (p= 0.04). CONCLUSIONS: Dexloxiglumide accelerates gastric
      emptying and delays proximal but not overall CT in patients with C-IBS.
      Dexloxiglumide does not accelerate transit in C-IBS. The role of CCK-1 gene
      polymorphisms in delaying gastric emptying and in determining response to therapy
      deserves further study.

PMID- 15743366
TI  - Clinical response to tricyclic antidepressants in functional bowel disorders is
      not related to dosage.
AB  - BACKGROUND: As shown in the per protocol analysis of a recent randomized,
      controlled trial, when tolerated, Desipramine (DES) is effective over placebo
      (PLA) in treating moderate-to-severe functional bowel disorders (FBD). Clinical
      experience suggests that the benefit from tricyclic antidepressants (TCA) in FBD
      can be achieved at doses lower than those used to treat major depression. Within
      psychiatry, when using higher dosage of TCAs, plasma levels can be used to adjust
      daily dosage to optimize a treatment response. However, in FBD, it is not known
      whether plasma levels at the lower dosage are similarly related to a clinical
      response. AIM: To determine in treating FBD, whether DES blood levels or dose
      taken can predict a clinical response. METHODS: As part of a study of 12 wk of
      antidepressant and psychological treatment in 431 patients with FBD at UNC and U
      of Toronto, we studied those participants who completed treatment (per protocol
      analysis) taking DES (N = 97, dose 50-150 mg/day) or pill placebo (PLA) (N = 55 1
      3 pills/day). The primary outcome measure was defined as a composite score
      (Satisfaction with Treatment, McGill Pain Questionnaire, Global Well-being, and
      IBS-QOL). The composite score was correlated with: (i) DES plasma levels at week
      6, and (ii) number of pills taken over the duration of the 12-wk treatment
      period. In addition, we also compared DES dose with DES plasma levels. RESULTS:
      There was a modest correlation between mean DES dose at weeks 5 and 6 and DES
      blood level at week 6 (R = 0.2 p < 0.07). However, there were no significant
      correlations between the composite score either with DES dose or with DES blood
      levels. CONCLUSIONS: Detectable blood levels of DES are associated with a
      clinical response in FBD. However, with dosages up to 150 mg, there is no
      relationship between total dose or plasma level and the clinical response.

PMID- 15743367
TI  - Temporal trends in new diagnoses of colorectal cancer with obstruction,
      perforation, or emergency admission in Ontario: 1993-2001.
AB  - OBJECTIVES: Previous studies have shown that patients newly diagnosed with
      colorectal cancer requiring emergency admission to hospital or presenting with
      obstruction or perforation (defined here as OPE) have advanced disease. None of
      these studies, however, has evaluated temporal trends in these adverse outcomes,
      which may reflect screening failures. We evaluated temporal trends in the
      proportion of Ontario patients with a new diagnosis of colorectal cancer and OPE.
      METHODS: Data were obtained from four sources: the Ontario Cancer Registry (OCR);
      the Canadian Institute for Health Information (CIHI) database, which contains
      diagnostic information on all patients discharged from hospitals; the Ontario
      Health Insurance Plan (OHIP) database, which records all physician claims in
      Ontario; and the Registered Persons Database, which contains demographic
      information on all Ontario residents covered under OHIP. We calculated the
      proportion of patients (>/=20 yr) with a new diagnosis of colorectal cancer
      recorded in CIHI who presented with OPE between 1993 and 2001. These patients
      were assigned to one of three cohort years: 1993-1995, 1996-1998, or 1999-2001.
      Those who received chemotherapy, radiotherapy, or palliative care before their
      first admission to hospital were excluded. We repeated the analysis using the
      number of OPE patients identified from CIHI in the numerator, and the number of
      patients (>/=20 yr) with a new diagnosis of colorectal cancer recorded in the OCR
      in the denominator. Adjusted risk of OPE was calculated using a logistic
      regression model. RESULTS: Between 1993 and 2001, 59,670 patients with a new
      diagnosis of colorectal cancer were recorded in the CIHI database and 54,103 in
      the OCR. The proportion of these patients with OPE recorded in the CIHI decreased
      significantly over time: 23.8% (95% CI = 23.2-24.4%) during 1993-1995, 19.4% (95%
      CI = 18.8-20.0%) during 1996-1998, and 18.1% (95% CI 17.6-18.6%) during 1999-2001
      (a 24% relative decrease over time). The relative decrease calculated from OCR
      data was similar. The adjusted relative decrease in the proportion of patients
      with OPE during 1993-2001 was 31%. CONCLUSIONS: Much greater emphasis on
      screening is needed since approximately 20% of patients with a new diagnosis of
      colorectal cancer in 1999-2001 presented with OPE.

PMID- 15743368
TI  - A novel educational strategy to enhance internal medicine residents' familial
      colorectal cancer knowledge and risk assessment skills.
AB  - BACKGROUND: Internal medicine residents are deficient in their knowledge about
      familial colorectal cancer (CRC) and thus unable to comply with appropriate
      screening guidelines. The objective of this study was to evaluate the
      effectiveness of a mixed educational program that incorporates both a didactic
      lecture (DL) and interactive, case-based seminar (ICBS), plus distribution of a
      personal digital assistant (PDA)-based risk assessment tool. METHODS: Internal
      medicine resident continuity care teams were randomly assigned to an intervention
      (9 teams; 43 residents) or control (11 teams; 39 residents) arm. Both groups
      participated in a DL addressing the current status of CRC screening for average,
      moderate, and high-risk groups. Intervention teams also participated in a 1-h pre
      clinic ICBS that included vignettes about patients at moderate or high risk of
      CRC because of family history, following which they received the risk assessment
      tool by e-mail. Knowledge and clinical risk assessment skills were evaluated
      using pre/posttests, patient exit interviews, and chart audits. RESULTS: Baseline
      test scores were similar for both groups (intervention, 51%vs control, 54%; p=
      0.35). Immediate post-ICBS scores (intervention group only) significantly
      increased to 82% (p < 0.001). Six-month post-ICBS scores declined for the
      intervention group but remained significantly higher than 6-month control group
      scores (63%vs 56%, p= 0.002), which were unchanged from baseline. No significant
      differences were observed with respect to family history-taking or documentation
      skills. CONCLUSION: A mixed educational program that incorporates both a DL and
      ICBS is more effective that the DL alone for increasing knowledge about familial
      CRC risk but may have limited influence on clinical risk assessment skills.

PMID- 15743369
TI  - Given capsule endoscopy in celiac disease: evaluation of diagnostic accuracy and
      interobserver agreement.
AB  - BACKGROUND AND AIMS: Capsule endoscopy (CE) has been increasingly used for
      diagnosing diseases of the small bowel. It is an attractive technique for
      assessing celiac disease (CD) because it is noninvasive and provides a close and
      magnified view of the mucosa of the entire small bowel. In this study, we
      evaluated the accuracy of CE and interobserver agreement in recognizing villous
      atrophy (VA) using histopathology as the reference. We also explored the extent
      of small bowel involvement with CD and the relationship between the length of the
      affected bowel and the clinical presentation. METHODS: Ten CD patients with
      histologically proven VA and the same number of controls were subjected to CE.
      Four, blinded to histology findings, investigators (two with and two without
      prestudy CE experience) were asked to diagnose VA on CE images. RESULTS: Based on
      assessment of all four investigators, the overall sensitivity, specificity, PPV,
      and NPV of CE in diagnosing VA were 70%, 100%, 100%, and 77%, respectively. The
      sensitivity and the specificity of the test was 100% when the reports of
      experienced capsule endoscopists only were analyzed. The interobserver agreement
      was perfect (kappa= 1.0) between investigators with prestudy CE experience and
      poor (kappa= 0.2) between the investigators who had limited prestudy exposure to
      CE. Celiac patients with extensive small bowel involvement had typical symptoms
      of malabsorption (diarrhea, weight loss) as opposed to mild and nonspecific
      symptoms in patients whose disease was limited to the proximal small bowel. CE
      was tolerated well by all study participants with 95% reporting absence of any
      discomfort. CONCLUSIONS: Although based on a small sample size, the study
      suggests that CE may be useful in assessing patients with CD. Familiarity with CE
      technology appears to be a critical factor affecting the accuracy of the test.
      Larger studies are warranted to more precisely define the advantages and
      limitations of CE in CD.

PMID- 15743370
TI  - Evolution of gastric electrical features and gastric emptying in children with
      Duchenne and Becker muscular dystrophy.
AB  - OBJECTIVES: Although muscular dystrophy (MD) affects primarily striated muscles,
      smooth muscle cells of the gastrointestinal tract may also be involved. We
      recorded gastric electrical activity and gastric emptying time (GET) in children
      with MD at initial presentation and at 3-yr follow-up in order to detect gastric
      motor abnormalities and study their evolution along the clinical course. METHODS:
      Twenty children with MD (median age: 4.6 yr; range age: 3-7 yr) were investigated
      by means of ultrasonography, for measuring GET, and by electrogastrography (EGG);
      70 children served as controls. RESULTS: Ten patients had Duchenne muscular
      dystrophy (DMD) and 10 Becker muscular dystrophy (BMD). GET was significantly
      more delayed in MD patients (DMD, median: 195 min; range 150-260 min; BMD,
      median: 197 min; range: 150-250 min) than in controls (median: 150 min; 110-180
      min; p < 0.05); it markedly worsened at the follow-up in DMD (median: 270 min;
      range 170-310 min; p < 0.001 vs controls) but not in BMD patients (median: 205
      min; 155-275 min; p < 0.05 vs DMD). Baseline EGG showed a significantly lower
      prevalence of normal rhythm and significantly higher prevalence of dysrhythmias
      in both groups of patients as compared to controls (% of normal rhythm: DMD 66.7
      +/- 8.2, BMB 67.2 +/- 11.5, controls 85.3 +/- 7.2, p < 0.001; % of tachygastria:
      DMD 28.4 +/- 8.0, BMB 29.8 +/- 12.3, controls 10.6 +/- 5.1, p < 0.001; % of
      dominant frequency instability coefficient: DMD 36.1 +/- 6.0, BMB 33.2 +/- 2.9,
      controls 17.9 +/- 7.1, p < 0.001); furthermore, no difference in fed-to-fasting
      ratio of the dominant EGG power was found between the two groups and controls
      (DMD 2.84 +/- 1.27, BMB 2.82 +/- 0.98, controls 3.04 +/- 0.85, ns). However, at
      the follow-up no significant change in the prevalence of normal rhythm and
      dysrhythmias occurred in both groups (ns vs baseline values), whereas only DMD
      patients showed a marked reduction in fed-to-fasting power ratio (0.78 +/- 0.59;
      p < 0.001 vs controls and BMD; p < 0.05 vs baseline), which correlated with the
      progressive neuromuscular weakness occurring in DMD subjects (r, 0.75; p <
      0.001). CONCLUSIONS: In children with MD, there is an early abnormality in
      gastric motility that is due to deranged regulatory mechanisms, whereas
      contractile activity of smooth muscle cells seems to be preserved. At the follow
      up, DMD patients exhibited a progressive failure in neuromuscular function, which
      was accompanied by a gastric motility derangement with worsening in GET and in
      EGG features suggesting an altered function of gastric smooth muscle cells.

PMID- 15743371
TI  - Pathogenesis and risk factors of small bowel adenocarcinoma: a colorectal cancer
      sibling?
AB  - Small bowel adenocarcinoma (SBA) is a very rare entity accounting for one-fourth
      of the small intestine neoplasms. Usually accompanied by nonspecific symptoms
      occurring late in the course of the disease, they are associated with a dismal
      prognosis. It appears that SBA shares several genetic characteristics with large
      bowel tumors, but also has unique features. The purpose of this article is to
      review pathogenesis and risks factors of SBA to better understand its molecular
      features as well as its resemblances and dissimilarities with colorectal cancer
      (CRC). Better understanding of sporadic and hereditary genetic pathways
      potentially involved will undoubtedly lead to better prevention and therapeutic
      management of this rare but aggressive disease.

PMID- 15743372
TI  - Hepatitis C virus-induced hepatocellular steatosis.
AB  - Two distinct forms of hepatocellular steatosis can be seen in patients with
      chronic hepatitis C virus (HCV) infection. Classical metabolic risk factors for
      hepatocellular steatosis account for the vast majority of cases of steatosis in
      patients infected by non-genotype 3 HCV strains. In contrast, in patients
      infected by HCV genotype 3, steatosis is generally induced by the virus itself
      through a direct cytopathic effect, the mechanisms of which remain debated. Mixed
      forms of steatosis can also be seen in HCV genotype 3-infected patients with
      metabolic risk factors. Hepatocellular steatosis appears to be associated with
      more rapid progression of hepatic fibrosis. However, it is unclear whether this
      association is due to steatosis itself, or rather to metabolic and host factors
      that promote steatosis and fibrosis concomitantly. This review discusses current
      knowledge of HCV-induced steatosis and its relation to chronic HCV-associated
      liver disease.

PMID- 15743373
TI  - Chronic hepatitis C treatment patterns in African American patients: an update.
AB  - There are large racial disparities in the incidence of chronic hepatitis C virus
      (HCV) infection in the United States. The prevalence of HCV, and the prevalence
      of infection with HCV genotype 1, is higher among African Americans than among
      other ethnic groups. African Americans also have a higher incidence of
      complications of HCV infection, including a higher incidence of antibodies to HCV
      RNA and higher incidences of occurrence of and mortality from hepatocellular
      carcinoma. Combination therapy with pegylated interferons and ribavirin has
      increased the sustained virologic response (SVR) rates, and decreased the rates
      and severity of adverse events, over those observed with standard interferons,
      with or without ribavirin, although SVR rates with peginterferons plus ribavirin
      are lower in African Americans than in other ethnic groups. A recent clinical
      trial of peginterferon alpha-2a plus ribavirin in African American patients
      resulted in a higher SVR rate, 26%, than observed previously, and 90% of patients
      showed stabilization or improvement in fibrosis. No host or viral genetic
      differences have yet been identified to explain the racial disparities in
      incidence of HCV or response to treatment, but clinical trials are currently
      ongoing to identify these factors. Because treatment with pegylated interferons
      plus ribavirin yields improved SVR rates with good tolerability, while the basis
      for lower response rates in African Americans is not yet known, it is recommended
      that all patients with chronic HCV infection, regardless of ethnic or racial
      background, receive combination therapy.

PMID- 15743374
TI  - Pneumomediastinum following Enteryx injection for the treatment of
      gastroesophageal reflux disease.
AB  - We describe the case of a 68-year-old female who developed pneumomediastinum
      following the "Enteryx" procedure for the treatment of gastroesophageal reflux
      disease (GERD). The patient required hospitalization and parenteral antibiotics
      and responded favorably to a conservative approach. Similar complications have
      been observed with other endoscopic treatment modalities for GERD such as Stretta
      and suturing techniques. Our patient represents the third reported case of a
      serious complication after Enteryx implantation.

PMID- 15743375
TI  - Endoscopic sedation.

PMID- 15743377
TI  - Interferon alpha-2b and ribavirin for patients with chronic hepatitis C and
      normal ALT.

PMID- 15743380
TI  - Postinfectious IBS.

PMID- 15743383
TI  - Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and
      central circulation in man.
AB  - AIM: Despite numerous in vitro and animal studies, circulatory effects and
      mechanisms responsible for the vasoconstriction seen during hyperoxaemia are yet
      to be ascertained. The present study set out to: (i) set up a non-invasive human
      model for the study of hyperoxia-induced cardiovascular effects, (ii) describe
      the dynamics of this effect and (iii) determine whether hyperoxaemia also, by
      vasoconstriction alters oxygen consumption (O(2)). METHODS: The study comprised
      four experiments (A, B, C and D) on healthy volunteers examined before, during
      and after 100% oxygen breathing. A: Blood flow (mL min(-1).100 mL(-1) tissue),
      venous occlusion plethysmography was assessed (n = 12). B: Blood flow was
      recorded with increasing transcutaneous oxygen tension (P(tc)O(2)) levels (dose
      response) (n = 8). C: Heart rate (HR), stroke volume, cardiac output (CO) and
      systemic vascular resistance (SVR) was assessed using echocardiography (n = 8).
      D: O(2) was measured using an open circuit technique when breathing an air-O(2)
      mix (fraction of inhaled oxygen: F(i)O(2) = 0.58) (n = 8). RESULTS: Calf blood
      flow decreased 30% during O(2) breathing. The decrease in calf blood flow was
      found to be oxygen dose dependent. A similar magnitude, as for the peripheral
      circulation, of the effect on central parameters (HR/CO and SVR) and in the time
      relationship was noted. Hyperoxia did not change O(2). An average of 207 (93) mL
      O(2) per subject was washed in during the experiments. CONCLUSION: This model
      appears suitable for the investigation of O(2)-related effects on the central and
      peripheral circulation in man. Our findings, based on a more comprehensive
      (central/peripheral circulation examination) evaluation than earlier made,
      suggest significant circulatory effects of hyperoxia. Further studies are
      warranted to elucidate the underlying mechanisms.

PMID- 15743384
TI  - The effects of different air velocities on heat storage and body temperature in
      humans cycling in a hot, humid environment.
AB  - AIM: The purposes of this study were to determine (i) the effects of different
      facing air velocities on body temperature and heat storage during exercise in hot
      environmental conditions and (ii) the effects of ingesting fluids at two
      different rates on thermoregulation during exercise in hot conditions with higher
      air velocities. METHODS: On five occasions nine subjects cycled for 2 h at 33.0
      +/- 0.4 degrees C with a relative humidity of 59 +/- 3%. Air velocity was
      maintained at 0.2 km h(-1) (0 WS), 9.9 +/- 0.3 km h(-1) (10 WS), 33.3 +/-2.2 km
      h(-1) (100 WS) and 50.1 +/- 3.2 km h(-1) (150 WS) while subjects replaced 58.8 +/
      6.8% of sweat losses. In the fifth condition, air velocity was maintained at
      33.7 +/- 2.2 km h(-1) and subjects replaced 80.0 +/- 6.8% of sweat losses (100.80
      WS). RESULTS: Heat storage, body temperature and rating of perceived exertion
      were higher in 0 and 10 WS compared with all other conditions. There were no
      differences in any measured variable between 100 and 150 WS, or between 100 and
      100.80 WS. Thus, the evaporative capacity of the environment is increased with
      higher air velocities, reducing heat storage and body temperature. At higher air
      velocities, a higher rate of fluid ingestion did not influence heat storage, body
      temperature or sweat rate. CONCLUSION: The finding of previous laboratory studies
      showing a beneficial effect of high rates of fluid ingestion on thermoregulation
      during exercise in hot, humid, windstill conditions cannot be extrapolated to out
      of-doors exercise in which facing air velocities are seldom lower than the
      athlete's rate of forward progression.

PMID- 15743385
TI  - Neuronal nitric oxide synthase and splanchnic blood flow in anaesthetized rats.
AB  - AIMS: To evaluate to what extent the neuronal form of constitutive nitric oxide
      synthase (nNOS) contributes to the blood perfusion of splanchnic organs,
      including the islets of Langerhans. METHODS: The nNOS inhibitor 7-nitroindazole
      (300 mg kg(-1) i.p.) was administered to anaesthetized Sprague-Dawley rats, some
      of which were pre-treated with the ganglionic blocker hexamethonium (20 mg kg(-1)
      i.v.) The blood perfusion of the splanchnic organs, including the pancreatic
      islets was then measured with a microsphere technique. RESULTS: Nitroindazole
      decreased total pancreatic, duodenal and renal blood flow, whereas pancreatic
      islet, colonic and adrenal blood flows were unchanged. A slight increase in mean
      arterial blood pressure was seen after nitroindazole treatment. Nitroindazole did
      not affect blood glucose or serum insulin concentrations. In separate
      experiments, hexamethonium affected none of the studied blood flow values,
      suggesting that the effects of nNOS-inhibition were not mediated from the nervous
      system. CONCLUSION: Nitric oxide derived from the activity of nNOS contributes to
      the blood perfusion in the upper portions of the gastrointestinal tract, viz. the
      parts supplied by the cranial mesenteric artery, and the kidneys, whilst no
      effects are seen on colonic or adrenal blood flow. Pancreatic islet blood flow
      was unaffected by nNOS inhibition, thereby suggesting that NO derived from the
      other isoforms of NOS maintains the high basal islet blood perfusion.

PMID- 15743387
TI  - Effect of 2 weeks of endurance training on uncoupling protein 3 content in
      untrained human subjects.
AB  - AIM: The mitochondrial uncoupling protein-3 (UCP3) is able to lower the proton
      gradient across the inner mitochondrial membrane, thereby uncoupling substrate
      oxidation from ATP production and dissipating energy as heat. What the effect of
      endurance training on UCP3 is, is still controversial. Endurance-trained athletes
      are characterized by lower levels of UCP3, but longitudinal studies in rodents
      reported no effect of endurance training on muscular UCP3 levels. Here, we
      examined the effect of a 2-week training programme on skeletal muscle UCP3
      protein content in untrained human subjects, and hypothesized that UCP3 will be
      reduced after the training programme. METHODS: Nine untrained men [age: 23.3 +/-
      3.2 years; BMI: 22.6 +/- 2.6 kg m(-2); maximal power output (W(max)): 3.8 +/- 0.6
      W kg(-1) body weight] trained for 2 weeks. Before and at least 72 h after the
      training period, muscle biopsies were taken for determination of UCP3 protein
      content. RESULTS: UCP3 protein content tended to be lower after the training
      programme [95 +/- 10 vs. 109 +/- 12 arbitrary units (AU), P = 0.08]. Cytochrome c
      content tended to increase with 33% in response to endurance training (52 +/- 6
      vs. 39 +/- 6 AU, P = 0.08). The ratio UCP3 relative to cytochrome c tended to
      decrease significantly upon endurance training (2.0 +/- 0.4 vs. 3.2 +/- 0.6 AU, P
      = 0.01). CONCLUSION: A short-term (2-week) endurance training programme decreased
      UCP3 protein levels and significantly reduced the ratio of UCP3 to cytochrome c.

PMID- 15743386
TI  - Role of Na,K pumps in restoring contractility following loss of cell membrane
      integrity in rat skeletal muscle.
AB  - BACKGROUND AND AIM: In skeletal muscles, electrical shocks may elicit acute loss
      of force, possibly related to increased plasma membrane permeability, induced by
      electroporation (EP). We explore the role of the Na(+),K(+) pumps in force
      recovery after EP. METHODS: Isolated rat soleus or extensor digitorum longus
      (EDL) muscles were exposed to EP paradigms in the range 100-800 V cm(-1), and
      changes in tetanic force, Na(+),K(+) contents, membrane potential, (14)C-sucrose
      space and the release of the intracellular enzyme lactic acid dehydrogenase (LDH)
      were characterized. The effects of Na(+),K(+) pump stimulation or inhibition were
      followed. RESULTS: Electroporation caused voltage-dependent loss of force,
      followed by varying rates and degrees of recovery. EP induced a reversible loss
      of K(+) and gain of Na(+), which was not suppressed by tetrodotoxin, but
      associated with increased (14)C-sucrose space and release of LDH. In soleus, EP
      at 500 V cm(-1) induced complete loss of force, followed by a spontaneous,
      partial recovery. Stimulation of active Na(+),K(+) transport by adrenaline, the
      beta(2)-agonist salbutamol, calcitonin gene-related peptide (CGRP) and dibutyryl
      cyclic AMP increased initial rate of force recovery by 183-433% and steady-state
      force level by 104-143%. These effects were blocked by ouabain (10(-3) m), which
      also completely suppressed spontaneous force recovery. EP caused rapid and marked
      depolarization, followed by a repolarization, which was accelerated by
      salbutamol. Also in EDL, EP caused complete loss of force, followed by a
      spontaneous partial recovery, which was markedly stimulated by salbutamol.
      CONCLUSION: Electroporation induces reversible depolarization, partial rundown of
      Na(+),K(+) gradients, cell membrane leakage and loss of force. This may explain
      the paralysis elicited by electrical shocks. Na(+),K(+) pump stimulation promotes
      restoration of contractility, possibly via its electrogenic action. The major new
      information is that the Na(+),K(+) pumps are sufficient to compensate a simple
      mechanical leakage. This may be important for force recovery in leaky muscle
      fibres.

PMID- 15743389
TI  - Changes in triceps surae muscle architecture with sarcopenia.
AB  - AIM: To investigate whether sarcopenia was evenly distributed among the three
      components of the triceps surae (TS) muscle group. METHODS: Muscle volume (VOL),
      fibre fascicle length (Lf), pennation angle (theta) and physiological cross
      sectional area (PCSA = VOL/Lf) were measured in vivo for the lateral (GL) and
      medial (GM) heads of the gastrocnemius muscles and for the soleus muscle (SOL),
      in 15 young males (YM, aged 25.3 +/- 4.5 years) and 12 elderly males (EM aged
      73.8 +/- 4.4 years). RESULTS: In the EM, VOL of all three muscles was
      significantly smaller than in the YM; differences were: 27% for the GL (P <
      0.01), 29% for the GM (P < 0.01) and 17% for the SOL (P < 0.05). In total, TS VOL
      was 22% smaller in EM than in YM (P < 0.01). In the EM, values of theta were
      significantly smaller than in the YM; by 15-18% for the GL, GM and SOL (P <
      0.05). In the EM, Lf of the GM was 16% smaller than in the YM (P < 0.01); no
      significant differences were found in the other muscles. PCSA of the GL and GM
      were both found to be smaller in EM by 19% (P < 0.01) and 14.5% (P < 0.05),
      respectively. No difference was observed in the SOL PCSA between YM and EM.
      Interestingly, probably because of the prevalent contribution of the SOL to PCSA
      distribution of each muscle to the TS PCSA, the relative TS PCSA was not
      different between YM and EM. Furthermore, the Lf/muscle length ratio did not
      differ between YM and EM. CONCLUSION: The present study shows that the relative
      PCSA composition of the TS is maintained with ageing and that the PCSA is scaled
      down harmonically with the decrease in muscle volume and fascicle length. Such
      observation suggests that the relative contribution of the components of the TS
      muscle to the total force developed by this muscle group is maintained with
      ageing.

PMID- 15743388
TI  - Relationship between protein O-linked glycosylation and insulin-stimulated
      glucose transport in rat skeletal muscle following calorie restriction or
      exposure to O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate.
AB  - AIMS AND BACKGROUND: Protein O-linked glycosylation is regulated in vivo by the
      concentration of hexosamine substrates. Calorie restriction (60% of ad libitum
      intake) for 20 days causes decreased UDP-N-acetylhexosamine levels and increased
      insulin-mediated glucose transport in rat skeletal muscle. Conversely, prolonged
      incubation (19 h) of muscle with O-(2-acetamido-2-deoxy-D
      glucopyranosylidene)amino-N-phenyl-carbamate (PUGNAc; an inhibitor of N-acetyl
      beta-D-glucosaminidase) is characterized by increased O-linked glycosylation and
      insulin resistance. We aimed to determine the calorie restriction effect on O
      linked glycosylation and characterize the temporal relationship between PUGNAc
      induced O-linked glycosylation and insulin resistance. HYPOTHESIS: A calorie
      restriction protocol characterized by decreased muscle hexosamine levels will
      result in a global reduction in O-linked glycosylated proteins in muscle, and
      PUGNAc-induced insulin resistance will coincide with increased O-linked
      glycosylation. METHODS: Plantaris muscle and liver from rats (ad libitum or
      calorie restricted) were analysed for O-linked glycosylation using two antibodies
      against different O-linked N-acetylglucosamine epitopes. Also, rat epitrochlearis
      muscles were incubated for 8.5 h +/- 100 mum PUGNAc prior to measurement of
      [(3)H]-3-O-methylglucose transport and O-linked glycosylation. RESULTS: Calorie
      restriction did not alter protein O-linked glycosylated levels in muscle or
      liver. Incubation with PUGNAc for 8.5 h resulted in increased in O-linked
      glycosylation but unaltered basal or insulin-stimulated glucose transport.
      CONCLUSIONS: The delay between O-linked glycosylation and insulin resistance in
      muscle incubated with PUGNAc suggests an indirect, relatively slow mechanism for
      insulin resistance. The effect of calorie restriction on insulin action in muscle
      is unlikely to be the direct result of a global change in protein O-linked
      glycosylation.

PMID- 15743391
TI  - Importance of the renin-angiotensin system in the regulation of arterial blood
      pressure in conscious mice and rats.
AB  - AIM: The present experiments were designed to determine the mechanism(s) for
      increased sensitivity to blockade of the renin-angiotensin system in mice in
      comparison with rats. METHODS: Mice and rats, with indwelling femoral arterial
      and venous catheters, were chronically administered angiotensin II or
      pharmacological inhibitors of the renin-angiotensin system as sodium intake was
      altered. RESULTS: Increasing sodium intake led to suppression of circulating
      renin, angiotensin II, and aldosterone in rats and mice in the absence of
      alterations in arterial blood pressure. Additional experiments demonstrated that
      continuous intravenous infusion of angiotensin II (20 ng kg(-1) min(-1))
      significantly increased arterial blood pressure by approximately 35 mmHg in
      conscious rats at all levels of sodium intake (n = 6). In contrast, arterial
      pressure was unaffected by angiotensin II infusion in conscious mice under
      conditions of low sodium intake, although arterial pressure was increased by 16
      mmHg when mice were administered a high sodium intake while infused with
      angiotensin II (n = 6). In comparison, blockade of the endogenous renin
      angiotensin system led to significantly greater effects on arterial pressure in
      mice than rats. Continuous infusion of captopril (30 microg kg(-1) min(-1)) or
      losartan (100 microg kg(-1) min(-1)) resulted in a 55-90% greater fall in blood
      pressure in conscious mice in comparison with conscious rats. CONCLUSION: The
      present studies indicate that arterial pressure in mice is more dependent upon
      the endogenous renin-angiotensin system than it is in rats, but mice are more
      resistant to the hypertensive effects of exogenous angiotensin II.

PMID- 15743390
TI  - Short-term endurance training results in a muscle-specific decrease of myostatin
      mRNA content in the rat.
AB  - AIM: Myostatin has been characterized as a negative regulator of skeletal muscle
      growth. To examine a probable function of myostatin during the adaptation of
      skeletal muscle in response to training, we analysed the effect of short-term
      endurance training on myostatin and insulin-like growth factor-I (IGF-I) mRNA
      contents in rat skeletal muscles. To assess the impact of the training stimulus,
      mRNA levels of metabolic genes were analysed simultaneously. METHODS: Male Wistar
      rats were trained for 5 days by swimming, while another group remained untrained.
      Myostatin, IGF-I, glucose transporter 4 (GLUT4), hexokinase II (HK II) and
      hydroxyacyl-CoA dehydrogenase (HAD) mRNA levels were determined by real-time
      reverse transcriptase-polymerase chain reaction (RT-PCR) in gastrocnemius, vastus
      lateralis and soleus muscles. A time course experiment was conducted, in order to
      examine transient changes of myostatin mRNA contents in gastrocnemius 7 and 24 h
      after one-swimming session as well as 24 h after a 3-day swimming training.
      RESULTS: No significant changes in IGF-I and GLUT4 mRNA levels were found in any
      of the muscles analysed. mRNA contents of myostatin were significantly reduced in
      gastrocnemius and vastus lateralis but not in soleus. In agreement to this
      pattern, we found significantly higher mRNA levels of HK II and HAD in the
      trained group. The time course experiment revealed significantly reduced
      myostatin mRNA contents in gastrocnemius 7 but not 24 h post-exercise. The 3-day
      swimming training resulted also in significantly lower myostatin mRNA levels in
      the trained group. CONCLUSION: This study demonstrated that short-term endurance
      training may modulate myostatin mRNA levels, implying a probable role of
      myostatin in remodelling of skeletal muscle in response to training.

PMID- 15743392
TI  - Short-term distribution of Cs in relation to Cr-EDTA after intravenous dose in
      goats.
AB  - AIM: The aim of this study was to gather information about the short-term rate of
      caesium uptake (incorporation) in different animal tissues and explain them with
      known physiological mechanisms affecting ion distribution. METHODS: Six goats
      were given an intravenous bolus containing (134)Cs as a tracer and (51)Cr-EDTA as
      an extracellular marker. After 30 min, the animals were killed and the activity
      concentration of radioactive isotopes in different tissues and fluid compartments
      were measured. RESULTS: The highest relative activity concentration of (134)Cs
      was found in kidney cortex, with a tissue/plasma-ratio around 50. In urine, the
      ratio varied between 5 and 28. In the salivary gland, cardiac muscle and small
      intestine the ratio was around 11, 7 and 6, respectively. The contents of small
      intestine had an average activity concentration five times that of plasma. In
      skeletal muscle the terminal activity concentration was surprisingly low, with a
      tissue/plasma ratio mostly far less than unity. Even in connective tissue and
      cartilage the terminal activity concentration was generally higher than in
      skeletal muscle. CONCLUSION: The rate of uptake of caesium varies widely from
      tissue to tissue. Many of these differences can be explained with differences in
      Na,K-ATPase activity. Also, perfusion and accessibility play a role in some
      tissues, like brain and possibly part of the skeletal muscles. The short-term
      distribution of caesium differs distinctly from the long-term distribution
      reported in literature.

PMID- 15743393
TI  - The fallacy of plasma noradrenaline spillover measurements.

PMID- 15743395
TI  - Exploring the potential of xenobiotic-metabolising enzymes as biocatalysts:
      evolving designer catalysts from polyfunctional cytochrome P450 enzymes.
AB  - 1. Biological catalysts have the advantage of being able to catalyse chemical
      reactions with an often exquisite degree of regio- and stereospecificity in
      contrast with traditional methods of organic synthesis. 2. The cytochrome P450
      enzymes involved in human drug metabolism are ideal starting materials for the
      development of designer biocatalysts by virtue of their catalytic versatility and
      extreme substrate diversity. Applications can be envisaged in fine chemical
      synthesis, such as in the pharmaceutical industry and bioremediation. 3. A
      variety of techniques of enzyme engineering are currently being applied to P450
      enzymes to explore their catalytic potential. Although most studies to date have
      been performed with bacterial P450s, reports are now emerging of work with
      mammalian forms of the enzymes. 4. The present minireview will explore the
      rationale and general techniques for redesigning P450s, review the results
      obtained to date with xenobiotic-metabolising forms and discuss strategies to
      overcome some of the logistic problems limiting the full exploitation of these
      enzymes as industrial-scale biocatalysts.

PMID- 15743396
TI  - Sphingosine kinase signalling in immune cells.
AB  - 1. Sphingolipids are potent second messengers modulating biochemical
      intracellular events and acting as ligands to mediate extracellular systems.
      Sphingosine kinase (SPHK) is the enzyme that phosphorylates sphingosine into
      sphingosine-1-phosphate (S1P), a potent bioactive sphingolipid. 2. The fact that
      SPHK is highly conserved from protozoa to mammals and is ubiquitous in living
      tissues reveals important roles of the SPHK pathway for the maintenance of health
      maintenance. This is also supported by comprehensive reviews on features of its
      main product, S1P, as having intracellular as well as extracellular roles,
      inducing a wide range of physiological responses from triggering Ca2+ release
      from internal stores to promoting growth and cell motility. 3. Immune cell
      activities have been shown to be modulated by the dynamic balance between
      ceramide, sphingosine and S1P, conceptualized as a rheostat. Cell proliferation,
      differentiation, motility and survival have been attributed to the regulatory
      actions of S1P. The properties of SPHK activity in immune cells are linked to the
      functions of triggered growth and survival factors, phorbol esters, hormones,
      cytokines and chemokines, as well as antigen receptors, such as FcgammaRI and
      FcepsilonRI. 4. Mechanisms of the SPHK signalling pathway are explored as new
      targets for drug development to suppress inflammation and other pathological
      conditions.

PMID- 15743397
TI  - Acute effects of hydrocortisone on plasma nitrate/nitrite activity and forearm
      vasodilator responsiveness in normal human subjects.
AB  - 1. The aim of the present study was to examine the acute effects of cortisol
      infusion on plasma nitrate/nitrite (NO) activity and forearm vascular
      responsiveness to acetylcholine. 2. We performed two randomized, placebo
      controlled, cross-over studies. Study A examined the effects of intravenous
      hydrocortisone (200 mg over a 3 h period) on blood pressure (BP) and plasma NO
      activity in six healthy male volunteers. Study B examined the effects of intra
      arterial hydrocortisone on cholinergic vasodilator responsiveness in six healthy
      male volunteers. Vasodilator responsiveness was measured by bilateral strain
      gauge plethysmography. 3. In study A, there was no significant change in BP
      during the hydrocortisone infusion. Comparing values obtained following 180 min
      infusion of hydrocortisone and control, there were significant increases in
      plasma cortisol (3441 +/- 342 vs 209 +/- 29 nmol/L, respectively; P < 0.001) and
      glucose (5.7 +/- 0.2 vs 4.6 +/- 0.2 mmol/L, respectively; P < 0.05) and a
      reduction in plasma renin concentration (PRC) (8.1 +/- 1.2 vs 11.0 +/- 1.8 pg/mL,
      respectively; P < 0.05) following hydrocortisone infusion. However, there were no
      significant changes in either plasma NO or in the endogenous NO synthase
      inhibitors asymmetrical and symmetrical dimethylarginine. 4. In study B, there
      was no significant change in BP or in cholinergic vasodilator responsiveness
      during the hydrocortisone infusion. 5. Short-term cortisol infusions do not alter
      biochemical or physiological markers of NO activity. If cortisol-induced
      hypertension is mediated by suppression of NO activity in humans, it seems likely
      that these changes take more than 3 h to become detectable.

PMID- 15743398
TI  - Protective effect of taurine against cyclophosphamide-induced urinary bladder
      toxicity in rats.
AB  - 1. In the present study, the effect of taurine, on cyclophosphamide (CP)-induced
      urinary bladder toxicity was investigated. 2. Administration of a single dose of
      CP (150 mg/kg, i.p.) induced cystitis, as manifested by marked congestion, oedema
      and extravasation in rat urinary bladder, as well as a marked desquamative damage
      to the urothium, severe inflammation in the lamina propria, focal erosions and
      polymorphonuclear leucocytes associated with occasional lymphocyte infiltration
      as determined by macroscopic and histopathological examination. 3. A significant
      decrease in the endogenous anti-oxidant compound glutathione and elevation of
      lipid peroxidation also resulted in rat urinary bladder tissue. 4.
      Cyclophosphamide-induced cystitis markedly affected the contractile function of
      the urinary bladder, as revealed by a significant inhibition of tissue
      responsiveness to acetylcholine (ACh) at different molar concentrations in vitro.
      5. Conversely, pretreatment with taurine (1% in drinking water to reach a dose of
      1 g/kg per day) for 7 days before and 1 day after CP injection produced a
      significant decrease in urinary bladder weight (oedema) and a marked decrease in
      vascular congestion and haemorrhage, as well as a profound improvement in
      histological structure. Moreover, taurine pretreatment resulted in a significant
      decrease in lipid peroxide in urinary bladder tissue and glutathione content was
      greatly restored. 6. Urinary bladder rings isolated from rats treated
      concurrently with taurine and CP showed a significant increase in their
      responsiveness to ACh compared with the CP group. 7. These results suggest that
      taurine offers a protective effect against CP-induced urinary bladder toxicity
      and may, therefore, decrease the limitation on its clinical application. These
      results merit extension and further investigation of the impact of taurine on CP
      antitumour activity.

PMID- 15743399
TI  - Effects of uninephrectomy on renal structural properties in spontaneously
      hypertensive rats.
AB  - 1. To investigate effects of a reduction in nephron numbers on renal structural
      properties in hypertension, either unilateral nephrectomy (UNX) or sham operation
      (SO) was performed at 5 weeks of age in spontaneously hypertensive rats (SHR) and
      Wistar-Kyoto (WKY) rats (n = 9 for each operation for each strain). 2. At 10-12
      weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR)
      relationships were determined for maximally vasodilated, perfused kidneys.
      Kidneys were then perfusion fixed for histological analysis. 3. In the SO groups,
      the slope of F-P (minimal renal vascular resistance, reflecting overall luminal
      dimensions of pre- and post-glomerular vasculature) was greater in SHR than in
      WKY rats. The threshold pressure for beginning filtration at P-GFR (preglomerular
      to post-glomerular vascular resistance ratio) was higher in SHR than in WKY rats,
      but the slope of P-GFR (glomerular filtration capacity) did not differ between
      the two strains. These results suggest that vascular narrowing occurred,
      especially in the preglomerular resistance vessels in the kidneys of SHR,
      although glomerular filtration capacity was normal. 4. In UNX animals, the
      following results were obtained: (i) the slope of F-P was not affected in either
      strain; (ii) the pressure for beginning filtration at P-GFR was unchanged in WKY
      rats, but was decreased in SHR; (iii) the slope of P-GFR increased in WKY rats,
      but a compensatory adaptive increase was missing in SHR; and (iv) histologically,
      small increases in the luminal cross-sectional area of interlobular arteries and
      glomerular tuft area were observed in both strains. However, the increase in
      vascular lumen was more pronounced in SHR, whereas glomerular enlargement was
      greater in WKY rats. 5. These results suggested that UNX attenuates vascular
      narrowing of the preglomerular resistance vessels and glomerular structural
      adaptations to UNX (i.e. increased filtering capacity and glomerular enlargement)
      are impaired in SHR.

PMID- 15743400
TI  - Protecting murine hearts from ischaemia-reperfusion using selective inhibitors of
      adenosine metabolism.
AB  - 1. By selectively modifying adenosine metabolism via adenosine deaminase or
      adenosine kinase inhibitors, it may be possible to enhance the receptor-mediated
      protective actions of adenosine in a site- and event-specific fashion. 2. We
      characterized cardioprotective actions of the adenosine deaminase inhibitor
      erythro-2-(2-hydroxy-3-non-yl)adenine (EHNA) and the adenosine kinase inhibitor
      iodotubercidin in C57/Bl6 mouse hearts subjected to 20 min global normothermic
      ischaemia and 40 min reperfusion. 3. Ventricular pressure development only
      recovered to 45 +/- 2% of baseline levels (67 +/- 5 mmHg) in untreated hearts,
      with sustained and pronounced diastolic contracture (25 +/- 2 mmHg). Treatment
      with 20 micromol/L EHNA increased recovery of ventricular pressure (107 +/- 9
      mmHg), reduced postischaemic diastolic pressure (13 +/- 1 mmHg) and reduced loss
      of lactate dehydrogenase (LDH; an indicator of necrotic damage) by 50% (9 +/- 2
      vs 19 +/- 2 IU/g). Adenosine kinase inhibition with 10 micromol/L iodotubercidin
      also improved pressure development (to 100 +/- 8 mmHg) and reduced LDH efflux (5
      +/- 2 IU/g). 4. Protective actions were mimicked by adenosine and inhibited by
      adenosine receptor antagonism (50 micromol/L 8-rho-sulfophenyltheophylline) and
      mitochondrial K(ATP) channel inhibition (50 micromol/L 5-hydroxydecanoate). 5.
      Coinfusion of the inhibitors, 'trapping' formed adenosine, failed to exert
      protection and, in some instances, was detrimental. Although substantial benefit
      was gained by these agents in hearts from young animals, neither inhibitor was
      effective in 'aged' hearts (18 months). 6. Our data demonstrate that adenosine
      deaminase or kinase inhibition substantially limits injury during ischaemia
      reperfusion. Protection involves adenosine receptor activation. However,
      cardioprotection via either enzyme inhibitor requires an alternative purine
      salvage pathway to be functional and was reduced in aged hearts known to be
      increasingly susceptible to ischaemic damage.

PMID- 15743401
TI  - Effect of dietary docosahexaenoic acid on the endothelium-dependent
      vasorelaxation in diabetic rats.
AB  - 1. The aim of the present study was to investigate the responses to acetylcholine
      (ACh; 3 nmol/L-30 micromol/L) and sodium nitroprusside (SNP; 3 nmol/L-30
      micromol/L) of precontracted aortic rings from diabetic rats supplemented with
      docosahexaenoic acid (DHA). 2. Diabetes was induced by streptozotocin (STZ; 55
      mg/kg). Diabetic and sham rats were fed, over a period of 8 weeks, either control
      diet or a DHA-supplemented diet. Aortic endothelial fatty acid composition was
      analysed by gas chromatography. The involvement of endothelial-derived nitric
      oxide (NO) and cyclo-oxygenase (COX) metabolites in response to ACh was assessed
      using the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (100
      micromol/L) and the COX inhibitor indomethacin (1 micromol/L), respectively. 3.
      The DHA-supplemented diet induced a small increase in n-3 polyunsaturated fatty
      acids (PUFA; P < 0.001) owing to the incorporation of DHA in the endothelial
      cells of sham animals (1.6 +/- 0.2% in the DHA group compared with traces in the
      control group; P < 0.001) and diabetic animals (1.3 +/- 0.2% in the DHA group
      compared with traces in control group; P < 0.001), without a decrease in n-6
      PUFA, despite a small decrease in arachidonic acid content (P < 0.05). Diabetes
      did not modify the incorporation of DHA in endothelial cells, but did
      significantly increase the arachidonic acid content (0.6 +/- 0.0 vs 0.4 +/- 0.1%
      in control group in the STZ and sham groups, respectively; P < 0.001).
      Acetylcholine-induced relaxation was significantly reduced in STZ groups compared
      with the sham groups (P < 0.001) and the DHA-supplemented diet did not modify
      these effects. In contrast, neither the DHA-supplemented diet nor diabetes
      affected the aortic relaxation induced by SNP. N(G)-Nitro-L-arginine methyl ester
      strongly inhibited the relaxant effects of ACh in the sham groups (P < 0.001) and
      abolished ACh-induced relaxation in the STZ groups (P < 0.001). The diet did not
      modify these effects. In the presence of indomethacin, the relaxation induced by
      ACh was decreased in the sham groups (P < 0.01), but not in the STZ groups. The
      DHA-supplemented diet did not have any effect on these responses. 4. In
      conclusion, these results suggest that, in the present study, the endothelial
      dysfunction occurring in the rat model of STZ-induced diabetes is associated with
      modifications of both the synthesis of COX derivatives and NO metabolism and is
      not affected by dietary supplementation with DHA.

PMID- 15743402
TI  - Inhibitory effect of sildenafil on rat duodenal contractility in vitro: putative
      cGMP involvement.
AB  - 1. Sildenafil citrate (Viagratrade mark; Pfizer, Sandwich, Kent, UK), a
      phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It
      relaxes both vascular and visceral smooth muscle. In order to assess the
      intestinal effects of sildenafil, we decided to investigate its actions on rat
      duodenal motor activity in vitro. 2. In isolated duodenal segments maintained in
      Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic
      effect on acetylcholine (ACh)-induced phasic contractions, with an IC50 value of
      26.7 micromol/L (95% confidence interval (CI) 2.0-55.3 micromol/L). 3. Sildenafil
      also relaxed the carbamylcholine (CCh)-induced sustained contraction with an
      IC(50) of 16.2 micromol/L (95% CI 9.5-27.6 micromol/L). Sildenafil produced
      significant additional relaxation of 25.2 +/- 8.1% of the CCh-induced
      contraction, beyond basal tone. 4. Sildenafil reduced the amplitude of
      spontaneous duodenal contractions with an EC50 of 9.6 micromol/L (95% CI 5.7-16.2
      micromol/L). This effect was significantly more potent than the effects of
      zaprinast and papaverine, which also reduced duodenal contractions with EC50
      values of 91.6 micromol/L (95% CI 46.0-182.2 micromol/L) and 78.5 micromol/L (95%
      CI 37.1-166.3 micromol/L), respectively. 5. In preparations treated previously
      with methylene blue (10 micromol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1
      one (ODQ; 10 micromol/L), the EC50 values for the sildenafil effect were
      significantly increased to 39.0 micromol/L (95% CI 23.9-63.4 micromol/L) and 43.8
      micromol/L (95% CI 24.5-78.3 micromol/L), respectively. These values were
      significantly greater than those obtained with sildenafil alone. 6. In
      conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal
      segments in vitro. The contractile inhibitory effect of sildenafil on rat
      isolated duodenum is probably due to intracellular cGMP accumulation as a result
      of its decreased degradation.

PMID- 15743403
TI  - Role of heme oxygenase/carbon monoxide pathway on the vascular response to
      noradrenaline in portal hypertensive rats.
AB  - 1. Portal hypertension (PH), a major syndrome in cirrhosis, producing
      hyperdynamic splanchnic circulation and hyperaemia. In order to elucidate the
      contribution of heme oxygenase to the vascular hyporeactivity, we assessed the
      activity of heme oxygenase-1 (HO-1), measured the in vivo pressure response to
      noradrenaline (NA) and investigated the effects of blocking the carbon monoxide
      (CO) and nitric oxide (NO) pathways in a prehepatic model of PH in rats. 2.
      Portal hypertension was induced by partial portal vein ligation (PPVL).
      Noradrenaline was injected intravenously. Liver, spleen and mesentery homogenates
      were prepared for measurement of HO-1 activity and expression. Four groups of
      rats were used: (i) a sham group; (ii) a PPVL group; (iii) a sham group
      pretreated with Zn-protoporphyrin IX (ZnPPIX); and (iv) a PPVL group pretreated
      with ZnPPIX. Each group was studied before and after treatment with the NO
      synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). 3. For basal
      pressures and the pressure response to NA, inhibition of CO and NO pathways by
      ZnPPIX and L-NAME, respectively, produced an increase in mean arterial pressure
      (MAP) in sham-operated and in PH rats. Similarly, when both inhibitors were used
      together in either sham or PPVL rats, a greater increase in MAP was observed. 4.
      These results, together with the increased HO-1 activity and expression only in
      the PH group, have led us to suggest that the heme oxygenase/CO pathway is
      involved in the vascular response to NA in PH rats.

PMID- 15743404
TI  - Effect of pregnancy on the roles of nitric oxide and prostaglandins in 5
      hydroxytryptamine-induced contractions in rat isolated thoracic and abdominal
      aorta.
AB  - 1. Vascular resistance and sensitivity to circulating pressor and vasoconstrictor
      substances are blunted during pregnancy. This has been attributed mainly to an
      increased production of endothelium-derived mediators. The aim of the present
      study was to determine whether pregnancy changes the relative participation of
      nitric oxide (NO) and prostaglandins (PG) in the modulation of the contractile
      response to 5-hydroxytryptamine (5-HT) in two anatomically distint segments of
      the rat aorta. 2. Full concentration-response curves to 5-HT were obtained in
      isolated rings from the thoracic and abdominal portion of the aorta from pregnant
      and non-pregnant rats in the presence and absence of the NO synthase (NOS)
      inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 10 micromol/L) or the PG
      synthesis inhibitor indomethacin (10 micromol/L). Cyclo-oxygenase (COX)-1, COX-2
      and endothelial (e) NOS protein expression were determined in the same tissues by
      immunoblot. 3. The effects of pregnancy were accentuated in the abdominal
      compared with the thoracic aorta. In addition, the relative participation of the
      NO and PG pathways seems to be changed during pregnancy. Although NO seems to be
      the mediator mainly responsible for the effect of pregnancy in the thoracic
      aorta, our results suggest a complex interaction between NO and PG in the
      abdominal aorta. Indomethacin significantly reduced the contractile response of
      both segments of the aorta, whereas expression of COX-1, COX-2 and eNOS were
      increased only in the abdominal segment of pregnant animals. 4. These results
      show that the effect of pregnancy is not homogeneous along the aorta. There seems
      to be a mutual interaction between PG and NO in the abdominal, but not in the
      thoracic, aorta from pregnant rats: the role of NO becomes evident in the absence
      of vasodilatory PG, whereas the participation of the latter increases in the
      absence of NO working as a compensatory mechanism.

PMID- 15743405
TI  - Experimental and clinical study of the combined effect of arterial stiffness and
      heart rate on pulse pressure: differences between central and peripheral
      arteries.
AB  - 1. Pulse pressure (PP) constitutes an independent predictor of cardiovascular
      events and mortality in various populations. Heart rate (HR) and arterial
      stiffness, in addition to their independent predictive value for cardiovascular
      complications, seem to interact with regard to the modification of PP. The aim of
      the present study was to investigate the association of PP with HR under
      different levels of arterial compliance (AC), revealing their synergistic
      effects. 2. Seventy-one normotensive and untreated hypertensive subjects were
      examined. Arterial compliance was measured by the 'area' method, whereas central
      blood pressures and wave reflections were evaluated using the Sphygmocor system
      (AtCor Medical, Sydney, NSW, Australia). A hydraulic Windkessel model was also
      used to evaluate the independent effect of HR and AC on PP. Peripheral PP was
      associated only with mean pressure and AC. In contrast, central PP was further
      related to HR (20 b.p.m. decrease in HR resulted in central PP augmentation by
      5.6 mmHg) regardless of mean pressure, stroke volume, age and gender. However,
      this association was statistically significant only for subjects with lower AC (<
      1.1 mL/mmHg) and not for those with more compliant arteries. These findings are
      also in accordance with the experimental data. 3. Aortic PP is affected to a
      greater degree by HR changes compared with peripheral PP. This response was
      observed only at high levels of arterial stiffness. 4. The present study provides
      the first evidence regarding the combined effect of AC and HR on aortic PP, which
      may lead to larger clinical or epidemiological studies aiming to optimization of
      drug treatment and to a possible reduction of cardiovascular risk.

PMID- 15743406
TI  - Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein
      and glycolytic enzyme activities in rat soleus muscle.
AB  - 1. The present study was designed to examine the role of calcineurin in muscle
      metabolic components by the administration of the specific calcineurin inhibitor
      cyclosporine A (CsA) to rats. 2. Male Wistar rats were divided into either a CsA
      treated group (CT) or a vehicle-treated group (VT). Cyclosporine A was
      administered subcutaneously to rats at a rate of 25 mg/kg bodyweight per day for
      10 successive days. Thereafter, changes in muscle enzyme activities and glucose
      transporter (GLUT)-4 and monocarboxylate transporter (MCT)-1 and MCT-4 proteins
      in the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles
      were examined. 3. There was a significant increase in MCT-1 and MCT-4 proteins in
      the soleus muscle in the CT group, but not in the EDL muscle. The activities of
      hexokinase, pyruvate kinase and lactate dehydrogenase in the soleus muscle also
      increased significantly in the CT group, but a similar increase in enzyme
      activity was not seen in EDL muscle. The activities of citrate synthase or malate
      dehydrogenase and the GLUT-4 protein content were not altered by CsA treatment in
      either the soleus or EDL muscles. 4. These results seem to imply that calcineurin
      negatively regulates the components of glucose/lactate metabolism, except for
      GLUT-4, especially in slow-twitch muscle.

PMID- 15743407
TI  - Oxidized low-density lipoprotein-induced apoptosis is attenuated by insulin
      activated phosphatidylinositol 3-kinase/Akt through p38 mitogen-activated protein
      kinase.
AB  - 1. The aim of the present study was to investigate whether p38 mitogen-activated
      protein kinase (p38 MAPK) is involved in oxidized low-density lipoprotein (oxLDL)
      induced apoptosis of human umbilical vein endothelial cells (HUVECs). We also
      sought to determine whether this apoptosis is regulated by the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway. 2. Low-density lipoprotein was
      oxidized with CuSO4 and used as oxLDL. Using HUVEC, we determined whether
      LDL/oxLDL induces apoptosis by DNA fragmentation and the cell cycle distribution
      (SubG1 method). The mechanism and activation of p38 MAPK and Akt were determined
      by western blot analysis. 3. The results showed that oxLDL induced DNA
      fragmentation, whereas cell cycle distribution showed that it also significantly
      increased the rate of cell death compared with the LDL group. SB203580
      significantly inhibited cell death induced by oxLDL, as did the administration of
      insulin. Western blot analysis showed the activation of p38 MAPK by oxLDL, but
      not with LDL. It was found that Akt was activated in the presence of insulin. In
      the presence of either SB203580 or insulin, activation of p38 MAPK was
      significantly inhibited compared with stimulation by oxLDL alone. However,
      application of both insulin and wortmannin resulted in no significant difference
      compared with HUVEC stimulated by oxLDL only. 4. The results showed that
      apoptosis in HUVEC can be induced by oxLDL and involves p38 MAPK. It was also
      demonstrated that insulin inhibited oxLDL-induced apoptosis and may inhibit the
      activation of p38 MAPK through the PI3K/Akt pathway.

PMID- 15743408
TI  - Effects of 15-deoxy-Delta12,14-prostaglandin J2 on the expression of Toll-like
      receptor 4 and 2 in the murine lung in the presence of lipopolysaccharide.
AB  - 1. Previously, we have demonstrated that 15-deoxy-Delta12,14-prostaglandin J2
      (15d-PGJ2) enhances acute lung injury induced by lipopolysaccharide (LPS) in
      mice. The enhancement in acute lung injury by 15d-PGJ2 was concomitant with the
      enhanced expression of several pro-inflammatory cytokines in the lung. However,
      other underlying mechanisms of this enhancement remain to be elucidated. The
      present study investigated the effects of 15d-PGJ2 on the expression of Toll-like
      receptor (TLR) 4 and 2 in the lung in the absence or presence of LPS. 2. In the
      present study, ICR mice were divided into four experimental groups that received
      (intratracheally) vehicle, LPS (125 microg/kg), 15d-PGJ2 (1 mg/kg) or 15d-PGJ2 +
      LPS. The mRNA expression of both TLR4 and 2 in the lung was evaluated 4 h after
      intratracheal administration. 3. 15-Deoxy-Delta12,14-prostaglandin J2 enhanced
      the mRNA expression of both TLR4 and 2 in the presence of LPS. 4. These results
      suggest that the enhancing effects of 15d-PGJ2 on LPS-induced acute lung injury
      may be explained, at least in part, by its effect on the lung expression of TLR4
      and 2.

PMID- 15743409
TI  - Functional overlap between RecA and MgsA (RarA) in the rescue of stalled
      replication forks in Escherichia coli.
AB  - Escherichia coli RecA protein plays a role in DNA homologous recombination,
      recombination repair, and the rescue of stalled or collapsed replication forks.
      The mgsA (rarA) gene encodes a highly conserved DNA-dependent ATPase, whose yeast
      orthologue, MGS1, plays a role in maintaining genomic stability. In this study,
      we show a functional relationship between mgsA and recA during DNA replication.
      The mgsA recA double mutant grows more slowly and has lower viability than a recA
      single mutant, but they are equally sensitive to UV-induced DNA damage. Mutations
      in mgsA and recA cause lethality in DNA polymerase I deficient cells, and
      suppress the temperature-dependent growth defect of dnaE486 (Pol III alpha
      catalytic subunit). Moreover, recAS25P, a novel recA allele identified in this
      work, does not complement the slow growth of DeltamgsA DeltarecA cells or the
      lethality of polA12 DeltarecA, but is proficient in DNA repair, homologous
      recombination, SOS mutagenesis and SOS induction. These results suggest that RecA
      and MgsA are functionally redundant in rescuing stalled replication forks, and
      that the DNA repair and homologous recombination functions of RecA are separated
      from its function to maintain progression of replication fork.

PMID- 15743410
TI  - Glucose-dependent cell size is regulated by a G protein-coupled receptor system
      in yeast Saccharomyces cerevisiae.
AB  - In the yeast, Saccharomyces cerevisiae, cell size is affected by the kind of
      carbon source in the medium. Here, we present evidence that the Gpr1 receptor and
      Gpa2 Galpha subunit are required for both maintenance and modulation of cell size
      in response to glucose. In the presence of glucose, mutants lacking GPR1 or GPA2
      gene showed smaller cells than the wild-type strain. Physiological studies
      revealed that protein synthesis rate was reduced in the mutant strains indicating
      that reduced growth rate, while the level of mRNAs for CLN1, 2 and 3 was not
      affected in all strains. Gene chip analysis also revealed a down-regulation in
      the expression of genes related to biosynthesis of not only protein but also
      other cellular component in the mutant strains. We also show that GPR1 and GPA2
      are required for a rapid increase in cell size in response to glucose. Wild-type
      cells grown in ethanol quickly increased in size by addition of glucose, while
      little change was observed in the mutant strains, in which glucose-dependent cell
      cycle arrest caused by CLN1 repression was somewhat alleviated. Our study
      indicates that the yeast G-protein coupled receptor system consisting of Gpr1 and
      Gpa2 regulates cell size by affecting both growth rate and cell division.

PMID- 15743411
TI  - Studies of Schizosaccharomyces pombe TFIIE indicate conformational and functional
      changes in RNA polymerase II at transcription initiation.
AB  - The general transcription factor TFIIE plays essential roles in transcription by
      RNA polymerase II (PolII). Despite recent progress, the elucidation of its
      precise mechanisms including biological functions awaits further
      characterization. We report the isolation and characterization of
      Schizosaccharomyces pombe TFIIE (spTFIIE). Like human and other eukaryotic TFIIE
      proteins, spTFIIE consists of alpha and beta subunits and the genes encoding both
      subunits are essential for viability. Chromatin immunoprecipitation assays
      demonstrated that spTFIIE localizes to promoters in vivo. Mutational analysis of
      the C-terminal basic helix-loop region of TFIIEbeta, which is involved in the
      transition from transcription initiation to elongation, revealed that
      transcription-defective mutants affected in this region are also cold sensitive.
      The spTFIIEbeta subunit binds both spTFIIEbeta and spTFIIEalpha but spTFIIEalpha
      binds only spTFIIEbeta. These results indicate that TFIIE forms an alpha2beta2
      heterotetramer in which two alphabeta heterodimers are connected via beta
      subunits. Further analysis of binding specificities showed that spTFIIEbeta binds
      the Rpb2 and Rpb12 subunits of PolII, whereas spTFIIEalpha predominantly binds
      Rpb5, which is located at the clamp region and changes conformation upon
      transcription initiation.

PMID- 15743412
TI  - Phosphorylation of PKC activation loop plays an important role in receptor
      mediated translocation of PKC.
AB  - Protein kinase C (PKC) is translocated to various cellular regions in a subtype
      and stimulation-dependent manner. Thereafter, the activated PKC phosphorylates
      its substrate and causes subsequent cellular responses (PKC targeting). The 3
      phosphoinositide-dependent protein kinase-1 (PDK1) has an essential role in the
      maturation of PKC by phosphorylating a threonine residue in the PKC activation
      loop. To elucidate the role of PDK1 in PKC targeting, we expressed mutant gamma-
      or delta-PKC fused with GFP (gamma- or delta-PKC-ALM (activation loop mutant)
      GFP), whose threonine residue in the activation loop was replaced with alanine,
      and compared their P2Y receptor-mediated translocation with wild-type PKC-GFP in
      CHO cells. ATP (1 mm) induced the transient translocation of wild-type gamma- or
      delta-PKC-GFP from cytoplasm to plasma membrane and following retranslocation
      from membrane to the cytoplasm. gamma- or delta-PKC-ALM-GFP was also translocated
      to plasma membrane, which was, however, retained at the membrane for a longer
      period than wild type. Similar results were observed in kinase-negative PKC
      mutants, indicating that the phosphorylation by PDK1 affects the retranslocation
      step of PKC by regulating the kinase activity. The simultaneous monitoring of
      [Ca2+]i and diacylglycerol (DG) levels with the translocation of PKC demonstrated
      that PKC-ALM induced the prolonged accumulation of DG, resulting in the prolonged
      retention of PKC-ALM at the plasma membrane. It is possible that PKC-ALM with
      decreased kinase activity could delay the conversion of DG at the plasma
      membrane. Our present study suggests that the activation loop phosphorylation
      plays an important role in receptor-mediated PKC targeting.

PMID- 15743413
TI  - The FWD1/beta-TrCP-mediated degradation pathway establishes a 'turning off
      switch' of a Cdc42 guanine nucleotide exchange factor, FGD1.
AB  - FWD1/beta-TrCP is the F-box protein that functions as the receptor subunit of the
      SCF(FWD1/beta-TrCP) ubiquitin ligase and has been shown to be responsible for the
      degradation of important signaling molecules such as IkappaBs and beta-catenin.
      Protein substrates of FWD1/beta-TrCP contain a consensus DSGPsiXS motif (where
      Psi represents a hydrophobic residue and X represents any amino acid).
      Recognition by FWD1/beta-TrCP requires phosphorylation of the conserved serines
      in that motif. Here we show that FGD1, a Cdc42 guanine nucleotide exchange factor
      (GEF), is a novel target of the SCF(FWD1/beta-TrCP) ubiquitin ligase. A mutant
      FGD1 protein, FGD1(SA), in which both of the critical serine residues in the
      DSGPsiXS motif have been replaced by alanines, does not interact with FWD1/beta
      TrCP and exhibits increased stability. Morphological changes induced by wild-type
      FGD1 (FGD1(WT)) are reduced by the co-expression of SCF(FWD1/beta-TrCP) whereas
      those induced by FGD1(SA) are not affected. FGD1(SA)-expressing cells show a
      higher level of cell motility than FGD1(WT)-expressing cells. We present a novel
      'turning off' mechanism for the inactivation of FGD1, an upstream regulator for
      Cdc42.

PMID- 15743414
TI  - 53BP2 induces apoptosis through the mitochondrial death pathway.
AB  - The p53 binding protein 2 (53BP2) has been identified as the interacting protein
      to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). The TP53BP2
      gene encodes two splicing variants, 53BP2S and 53BP2L, previously known as
      apoptosis stimulating protein 2 of p53 (ASPP2). We found that these 53BP2
      proteins are located predominantly in the cytoplasm and induce apoptosis as
      demonstrated by cleavage of poly ADP ribose polymerase (PARP) and annexin V
      staining. Furthermore, we demonstrate that 53BP2 is located in the mitochondria
      and induces apoptosis associated with depression of the mitochondrial trans
      membrane potential (DeltaPsim) and activation of caspase-9. From these findings
      we conclude that 53BP2 induces apoptosis through the mitochondrial death pathway.

PMID- 15743415
TI  - Tissue expression of four troponin I genes and their molecular interactions with
      two troponin C isoforms in Caenorhabditis elegans.
AB  - Gene duplication is a major genetic event that can produce multiple protein
      isoforms. Comparative sequence and functional analysis of related gene products
      can provide insights into protein family evolution. To characterize the
      Caenorhabditis elegans troponin I family, we analyzed gene structures, tissue
      expression patterns and RNAi phenotypes of four troponin I isoforms. Tissue
      expression patterns were determined using lacZ/gfp/rfp reporter gene assays. The
      tni-1, tni-2/unc-27 and tni-3 genes, each encoding a troponin I isoform, are
      uniquely expressed in body wall, vulval and anal muscles but at different levels;
      tni-4 was expressed solely in the pharynx. Expressing tni-1 and -2 gene RNAi
      caused motility defects similar to unc-27 (e155) mutant, a tni-2 null allele. The
      tni-3 RNAi expression produced egg laying defects while the tni-4 RNAi caused
      arrest at gastrulation. Overlay analyses were used to assay interactions between
      the troponin I and two troponin C isoforms. The three body wall troponin I
      isoforms interacted with body wall and pharyngeal troponin C isoforms; TNI-4
      interacted only with pharyngeal troponin C. Our results suggest the body wall
      genes have evolved following duplication of the pharynx gene and provide
      important data about gene duplication and functional differentiation of nematode
      troponin I isoforms.

PMID- 15743416
TI  - Effects of genetic ablation of bach1 upon smooth muscle cell proliferation and
      atherosclerosis after cuff injury.
AB  - Bach1 is a transcriptional repressor of the cytoprotective enzyme heme oxygenase
      1 (HO-1). Although HO-1 protects against atherosclerosis, the function of Bach1
      in this process is poorly understood. We isolated peritoneal macrophages and
      aortic smooth muscle cells (SMC) from wild-type and bach1-deficient mice. bach1
      Deficient macrophages expressed increased levels of HO-1 and showed elevated
      phagocytic activity when incubated with 0.75 microm microspheres. In SMC, bach1
      ablation resulted in increased expression of HO-1 and decreased proliferation in
      bromodeoxyuridine incorporation assay as compared with wild-type cells. The up
      regulated phagocytic activity and reduced SMC proliferation of bach1-deficient
      cells were not restored by Zinc (II) protoporphyrin IX, an inhibitor of HO,
      suggesting that HO-independent mechanisms are also involved in the regulation of
      phagocytosis of macrophages and proliferation of SMC by Bach1. In wild-type mice,
      cuff placement around femoral artery caused pronounced intimal proliferation
      without affecting the media, thus resulting in intimal to medial (I/M) volume
      ratio of 65.6%. bach1-deficient mice had less degree of intimal growth (I/M ratio
      of 45.6%). These results indicate that Bach1 plays a critical role in the
      regulation of HO-1 expression, macrophage function, SMC proliferation and
      neointimal formation. Bach1 may regulate gene expression in these cells during
      inflammation and atherogenesis.

PMID- 15743417
TI  - Difference in root canal length between Asians and Caucasians.
AB  - AIM: To investigate whether there is a racial difference in canal length between
      the Asians and Caucasians. METHODOLOGY: Five hundred and fifteen Asian patients
      who had received root canal treatment at the Yonsei University Hospital, Korea
      between 1995 and May 2001 and 324 Caucasoid patients who had received root canal
      treatment at the Graduate Endodontic Clinic at the University of Pennsylvania, US
      were selected. The clinical endodontic procedures at both clinics were similar.
      An electronic apex locator (Root-ZX; J. Morita Co., Kyoto, Japan) was used to
      measure the initial working lengths and this was verified by conventional
      radiography. The measurements from both Asian and Caucasian teeth were compared
      using a Student's t-test and a Mann-Whitney test. RESULTS: The mean difference in
      canal length of pooled teeth between the Asian and Caucasian teeth was 1.2 mm,
      with a range from 0 to 2.5 mm. The greatest difference was in the distobuccal
      canal (2.5 mm) of maxillary first molar teeth followed by the mesiolingual canal
      (2.3 mm) of mandibular second molar, the buccal canal (2.1 mm) of the maxillary
      second premolar, the maxillary first molar and the mandibular second molar.
      CONCLUSION: Tooth lengths in Asians were shorter than Caucasians.

PMID- 15743418
TI  - Influence of the pulpal components on human dentine permeability in vitro.
AB  - AIM: To examine the influence of the retained pulpal components on permeability
      of human dentine by monitoring drug diffusion. METHODOLOGY: Twelve intact dentine
      discs were prepared from freshly extracted human third molars. The dentine
      surface on the enamel side was etched with 10% polyacrylic acid for 30 s. The
      drug diffusion test was carried out before and after removal of the retained
      pulpal components. Each dentine disc was inserted between two plastic chambers;
      enamel- and pulpal-side chambers, which were filled with 0.05 mol L(-1) naproxen
      sodium (NA) and phosphate-buffered saline (PBS), respectively. After 10 min, the
      solution on the pulpal-side chamber was collected to determine the concentration
      of NA using a spectrophotometer. To remove the retained pulpal components and
      residual NA, the pulp chamber of each disc was washed out with PBS and placed in
      an ultrasonic cleaner. After removal of these components and the residual NA, the
      drug diffusion test was repeated. The inner surface of the pulp chamber was
      observed using scanning electron microscopy (SEM) before and after the removal of
      the retained pulpal components. RESULTS: The amount of NA that diffused through
      dentine into the pulp was significantly higher after the pulp chamber was washed
      out with PBS (paired t-test, P < 0.05). SEM observation demonstrated the presence
      of the retained pulpal components, odontoblastic layer and some parts of
      subodontoblastic zone, covering the surface of predentine. These components were
      removed after the pulp chamber was washed out with PBS followed by cleaning in an
      ultrasonic cleaner. CONCLUSIONS: The presence of retained pulpal components had a
      significant influence on drug diffusion through dentine discs.

PMID- 15743419
TI  - Frequency and type of canal isthmuses in first molars detected by endoscopic
      inspection during periradicular surgery.
AB  - AIM: To analyse the occurrence of canal isthmuses in molars following root-end
      resection. METHODOLOGY: The material consisted of 56 mandibular and 32 maxillary
      first molars subjected to periradicular surgery. Based on radiographic, clinical,
      as well as intraoperative status, only roots with associated pathological lesions
      were treated. In total, 124 roots were resected (80 mandibular and 44 maxillary
      molar roots). The cut root faces were inspected with a rigid endoscope following
      apical root-end resection. The number of canals as well as the presence and type
      of canal isthmuses were recorded. RESULTS: In maxillary first molars, 76% of
      resected mesio-buccal roots had two canals and an isthmus, 10% had two canals but
      no isthmus, and 14% had a single canal. All disto-buccal and palatal roots had
      one canal. In mandibular first molars, 83% of mesial roots had two canals with an
      isthmus. In 11%, two canals but no isthmus were present, and 6% demonstrated a
      single canal. Sixty-four per cent of distal roots had a single canal and 36% had
      two canals with an isthmus. CONCLUSIONS: This clinical study during periradicular
      surgery and intraoperative endoscopic examination of first permanent molars found
      a high frequency of canal isthmuses at the resection level. Endoscopic inspection
      also demonstrated that none of the isthmuses were filled, emphasizing the
      difficulty of orthograde instrumentation and root filling of canal isthmuses.

PMID- 15743420
TI  - Prevalence of persistent pain after endodontic treatment and factors affecting
      its occurrence in cases with complete radiographic healing.
AB  - AIMS: To (i) determine the prevalence of persistent dento-alveolar pain following
      nonsurgical and/or surgical endodontic treatment conducted in a teaching dental
      hospital and (ii) identify the risk factors associated with persistent pain after
      apparently successful root canal treatment. STUDY DESIGN: A total of 175
      patients/teeth were reviewed 12-59 months following treatment. The patients were
      examined clinically and radiographically and a detailed pain history obtained.
      Multiple logistic regression analysis was used to investigate the association
      between potential risk factors and persistent pain after successful endodontic
      treatment. RESULTS: The prevalence of persistent pain after successful root canal
      treatment was 12% (21/175). Treatment success was determined by the absence of
      clinical and radiographic signs of dental disease. The factors that were
      significantly (P < 0.05) associated with persistent pain following endodontic
      treatment were: 'duration of preoperative pain' [odds ratio (OR) = 8.6],
      'preoperative pain from the tooth' (OR = 7.8), 'preoperative tenderness to
      percussion' (OR = 7.8), 'previous chronic pain problems' (OR = 4.5), 'gender' (OR
      = 4.5) and 'history of painful treatment in the orofacial region' (OR = 3.8).
      'Type of treatment received (surgical or nonsurgical treatment)' showed
      borderline significance at the 10% level. CONCLUSIONS: The presence and duration
      of preoperative pain from the tooth site, lasting at least 3 months, a positive
      history of previous chronic pain experience or painful treatment in the orofacial
      region, and female gender were important risk factors associated with persistent
      pain after successful endodontic treatment.

PMID- 15743421
TI  - Outcome of root canal treatment using Thermafil and cold lateral condensation
      filling techniques.
AB  - AIM: To evaluate the outcome of root canal treatment (RCT) using either Thermafil
      (TF) or lateral condensation (LC) as filling technique, and to compare the time
      required for the treatment when either filling technique was used. METHODOLOGY:
      This study involved all patients attending the dental clinic of a university in
      Hong Kong who required primary, nonsurgical RCT. It was a prospective clinical
      trial involving 85 teeth in 79 patients aged 15-69 years (mean 48 +/- 12 years),
      which required root treatment and finally filling with either TF or LC by one of
      four dentists following a standard treatment protocol. The time used for the
      entire course of treatment was recorded. The treated teeth were examined both
      clinically and radiographically 3 years after the treatment by a single examiner
      who did not know their group assignment. RESULTS: A total of 85 teeth from 79
      patients were included in this study and 71 teeth from 64 patients were examined
      after 3 years. Thirty-four teeth were root filled with LC and 37 with TF. The
      overall attrition rate was 16% (14/85). There were 22 incisors and canines, 21
      premolars and 28 molars for evaluation. Post-treatment disease with clinical
      symptoms and/or radiographic radiolucency was observed in seven teeth (21%) of
      the LC group and in seven teeth (19%) in the TF group. There was no statistically
      significant difference (P > 0.05) for the presence of disease between the two
      groups. It was found that irrespective of the filling method used, teeth later
      restored with extracoronal restorations had a lower association with disease than
      those receiving intracoronal restorations (7% vs. 30%; P = 0.037). RCT took, on
      average, 20 min less when TF was used for filling compared with LC (98 min vs. 78
      min, P = 0.003). CONCLUSIONS: Using TF or LC in the filling of root canals did
      not result in significant difference in the clinical treatment outcome. TF
      consumed significantly less time than LC. The type of postendodontic restoration
      had a significant association with the presence of post-treatment disease.

PMID- 15743422
TI  - Dental pulp capping: effect of Emdogain Gel on experimentally exposed human
      pulps.
AB  - AIM: To investigate the effect of Emdogain Gel (Biora AB, Malmo, Sweden),
      consisting of a enamel matrix derivative (EMD) in a propylene glycol alginate
      (PGA) vehicle, on experimentally exposed human pulps and to register
      postoperative symptoms. METHODOLOGY: Nine pairs of contralateral premolars
      scheduled for extraction on orthodontic indications were included. Following a
      superficial pulp amputation performed with a small (016) diamond bur, either
      EMDgel or a mix of calcium hydroxide and sterile saline was placed at random in
      contact with the pulp wound. The subjects made records of symptoms and were also
      interviewed about pain/discomfort by a blinded examiner. After 12 weeks the teeth
      were extracted, prepared and subjected to light microscopic examination in which
      the inflammation and newly formed hard tissue in the pulp were analysed.
      Immunohistochemistry was performed using affinity-purified rabbit anti-EMD
      polyclonal antibodies. RESULTS: Postoperative symptoms were less frequent in the
      EMDgel-treated than in the calcium hydroxide-treated teeth, especially during the
      first six weeks. In the EMDgel-treated teeth, new tissue partly filled the space
      initially occupied by the gel and hard tissue was formed alongside the exposed
      dentine surfaces and in patches in the adjacent pulp tissue. EMD was detected in
      the areas where new hard tissue had been formed. The wound area of the EMDgel
      treated teeth exhibited inflammation in the majority of the teeth whereas less
      inflammation was seen in the calcium hydroxide-treated teeth where the hard
      tissue was formed as a bridge. CONCLUSIONS: In the EMDgel-treated teeth,
      postoperative symptoms were less frequent and the amount and pattern of hard
      tissue formation were markedly different than in the teeth treated with calcium
      hydroxide. However, the operative procedure and the formulation with EMD in a PGA
      vehicle do not seem to be effective for the formation of a hard tissue barrier.

PMID- 15743423
TI  - Copper-zinc superoxide dismutase activity in healthy and inflamed human dental
      pulp.
AB  - AIM: To examine copper-zinc superoxide dismutase (Cu, Zn-SOD) activity in
      clinically healthy and symptomatic human dental pulps. METHODOLOGY: Twenty-five
      systemically healthy patients, 14 females and 11 males (age: 13.1-34.6 years;
      mean: 21.7 +/- 6.3), were the source of the pulp tissue. The condition of the
      pulps was assessed using clinical and radiographic evaluation. The pulp tissue
      was collected by longitudinally grooving and splitting the teeth (if extracted)
      or during endodontic treatment, and were age- and sex-matched between the healthy
      and the irreversible symptomatic pulpitis tissue groups. Cu, Zn-SOD activity was
      determined through spectrophotometric methods and a Mann-Whitney test assessed
      the significance of differences between the groups. RESULTS: The enzyme
      activities were 144.8 +/- 42.2 and 68.1 +/- 25.0 U mg(-1) in the healthy and
      irreversible symptomatic pulp tissue, respectively. The difference between the
      groups was statistically significant (P < 0.001). CONCLUSIONS: These results
      demonstrate a potential role for Cu, Zn-SOD during dental pulp inflammation in
      humans.

PMID- 15743425
TI  - An overview of the antifungal properties of allicin and its breakdown products-
      the possibility of a safe and effective antifungal prophylactic.
AB  - Reports about the safe and successful intravenous (i.v.) use of garlic
      derivatives in China against invasive fungal infections have been made, but
      little has been done to seriously investigate the in vivo use of these
      derivatives in the West. Laboratories have demonstrated impressive in vitro MICs
      using allitridium, one of these derivatives, against a range of medically
      important fungi. In addition, it has been demonstrated that allitridium shows in
      vitro synergy with amphotericin B, one of the main i.v. antifungal agents. Some
      of the breakdown products of allicin, the main parent antifungal compound in
      garlic, have been investigated for their general antimicrobial, anticancer and
      anticholesterol properties, and it appears that there is a common mode of action
      that underlies these activities. It appears that these small molecules have the
      ability to cross cell membranes and combine with sulfur-containing molecular
      groups in amino acids and proteins, thus interfering with cell metabolism. It has
      been suggested that the reason human cells are not poisoned by allicin
      derivatives is that they contain glutathione, a sulfur-containing amino acid that
      combines with the allicin derivative, thus preventing cell damage. In addition to
      their biochemical mechanism, these derivatives appear to stimulate cellular
      immunity, an important ability lacking in conventional antifungal chemotherapy.
      These derivatives appear to be safe, cheap, wide-spectrum and immunostimulatory,
      as well as possibly synergistic with conventional antifungal therapy, making them
      ideal candidates for investigation into their use as prophylactic antifungal
      agents.

PMID- 15743424
TI  - New insights into the effect of amorolfine nail lacquer.
AB  - Despite improvements in antifungal strategies, the outcome of treating
      onychomycoses often remains uncertain. Several factors account for treatment
      failure, of which the pharmacokinetics and pharmacodynamics of the antifungal are
      of importance. The taxonomic nature and ungual location of the fungus cannot be
      neglected, besides the type of nail and its growth rate. In addition, the
      biological cycle of the fungus and the metabolic activity of the pathogen likely
      play a marked influence in drug response. The presence of natural antimicrobial
      peptides in the nail is also probably a key feature controlling the cure rates.
      There are many outstanding publications that cover the full spectrum of the
      field. The purpose of this review is to put in perspective some facets of
      activity of the topical treatment using amorolfine nail laquer. The antifungal
      activity of the drug is likely less pronounced in onychomycosis than that
      expected from conventional in vitro studies. However, the nail laquer formulation
      should reduce the propensity to form antifungal-resistant spores and limit the
      risk of reinfection.

PMID- 15743426
TI  - Antifungal effect of 5-aminolevulinic acid PDT in Trichophyton rubrum.
AB  - In the present investigation, we have shown for the first time that the
      onychomycosis-inducing dermatophyte Trichophyton rubrum was able to metabolize 5
      aminolevulinic acid (ALA) to protoporphyrin IX (PpIX) in liquid culture medium.
      We have established and optimized the culture conditions and could show the
      typical PpIX-induced red fluorescence which was evaluated qualitatively by Wood's
      light examination and fluorescent microscopic analysis. The optimum concentration
      of ALA was in the range of 1-10 mmol l(-1). If used in higher concentrations, ALA
      leads to a significantly reduced growth rate and absence of PpIX formation due to
      highly acidic conditions. The first observation of red fluorescence was detected
      between 10 and 14 days poststimulation with ALA, increasing thereafter.
      Fluorescent microscopic examinations demonstrated that formation of PpIX was
      restricted to selected parts of the fungal mycelium. Repeated application of ALA
      in order to achieve the highest formation of PpIX in T. rubrum failed, probably
      due to the sustained low pH values. ALA treatment and irradiation of T. rubrum
      clearly demonstrated the growth-inhibiting effect of ALA PDT, either leading to
      reduced numbers of colonies or reduced diameters of single fungal colonies.
      Summarizing our results, ALA PDT might be a promising approach in the reduction
      of T. rubrum colonization in onychomycosis.

PMID- 15743427
TI  - A novel mycological analysis valuable for evaluating therapeutic efficacy of
      antimycotics against experimental dermatophytosis in guinea pigs.
AB  - Although antimycotic effects are mainly evaluated with regard to whether or not
      the fungi grow from a specimen obtained from the drug-treated skin, the potential
      for discrepancies in skin specimens in which the fungi are grown has not been
      evaluated, in the experimental tinea model. In this study, to evaluate the
      therapeutic effectiveness of antimycotic agents against fungal skin infection, a
      novel form of mycological assessment, which focuses on the size of colonies grown
      from skin specimens was examined and developed. When microconidia of Trichophyton
      mentagrophytes were inoculated onto a Sabouraud dextrose agar (SDA) plate and
      incubated at 27 degrees C for 5 days, a linear relationship was observed between
      the growth area of mycelia and the logarithm of the quantity of microconidia.
      This relationship between the growth area and the logarithm of the number of T.
      mentagrophytes microconidia did not change with the addition of skin homogenate
      and/or keratin powder. Next, the number of fungi in skin blocks attendant upon
      experimental, cutaneous infection in guinea pigs was evaluated and analyzed via a
      calibration curve, determined based on a microconidium suspension of T.
      mentagrophytes. Estimates of severity of dermatophytic infection in experimental
      animals were parallel to, but more reliable than, results obtained via the
      conventional mycological method (fungus-positive skin ratio of treated skin) in
      culture studies of infected dermal tissues. This new analytical method may also
      be applicable to the in vivo assessment of the therapeutic effect against
      dermatophytosis experimentally produced in guinea pigs.

PMID- 15743429
TI  - Varied clinical manifestations of Penicillium marneffei in patients with human
      immunodeficiency virus: a report from south India.
AB  - Penicillium marneffei is a dimorphic fungus endemic to northeast India. This is
      the first report of penicilliosis from a hospital in south India. Three patients
      with diverse clinical manifestations who presented to a tertiary care hospital
      are described. High index of clinical suspicion and knowledge of 'local'
      microbiology is paramount in early diagnosis and timely treatment.

PMID- 15743428
TI  - Mycological examinations on the fungal flora of the chicken comb.
AB  - A total of 500 combs of adult chickens from two different locations in Germany
      (Hessen and Schleswig-Holstein) were clinically and mycologically examined. The
      chickens came from three battery cages (n = 79), one voliere system (n=32), six
      flocks maintained on deep litter (n = 69) and 12 flocks kept on free outdoor
      range (n=320). Twenty-two of the 500 chicken combs (4.4%) were found to have
      clinical signs: only non-specific lesions neither typical of mycosis nor of avian
      pox such as desquamation with crust formation, yellow to brown or black
      dyschromic changes, alopecia in the surrounding area and moist inflammation. Only
      seven of the 22 clinically altered combs showed a positive mycological result;
      the non-pathogenic and geophilic Trichophyton terrestre in one case and non
      pathogenic yeast in six cases. The following fungi were seen in the different
      housing systems: 13 dermatophytes (2.6% of 500 samples): 12 x T. terrestre, 1 x
      Trichophyton mentagrophytes, 11 isolates of Chrysosporium georgiae (2.2% of 500
      samples) and 149 isolates of yeasts (29.8%): Malassezia sympodialis: n = 52,
      Kloeckera apiculata: n = 33, Trichosporon capitatum (syn. Geotrichum capitatum):
      n = 23, Trichosporon cutaneum/Trichosporon mucoides: n = 12, Trichosporon inkin
      (syn. Sarcinosporon inkin): n = 8 and Candida spp.: n = 21, including pathogenic
      or possibly pathogenic species: Candida albicans: n = 3, Candida famata: n = 4,
      Candida guilliermondii: n = 3, Candida lipolytica: n = 3, Candida dattila: n = 2
      and one isolate each of Candida glabrata, Candida parapsilosis, Candida aaseri,
      Candida catenulata sive brumpti, Candida fructus and Candida kefyr sive
      pseudotropicalis. There is no stringent correlation between the clinical symptoms
      diagnosed on the chicken combs and the species of yeasts isolated. The causative
      agent of favus in chickens, Trichophyton gallinae, and the saprophytic yeast in
      pigeons, Cr. neoformans were not isolated. The most frequently isolated yeasts M.
      sympodialis and Kloeckera apiculata are suggested to be classified as members of
      the resident flora of the chicken comb.

PMID- 15743430
TI  - Cryptococcosis: the 1981-2000 epidemic.
AB  - The annual incidence of cryptococcosis during 1981-2000 was determined in
      subscribers of a large integrated health care program in Northern California and
      in those among them who were HIV positive. The incidence of cryptococcosis had
      been measured in this setting in the previous decade. The 20-year incidence per
      million person-years was 19.0 in males and 2.6 in females. In males, annual
      incidence rose sharply but irregularly from 1981 to 1992, then decreased
      irregularly. In females, trends were less marked, with maximum incidence in 1997.
      In HIV-positive patients cryptococcosis incidence was highest in 1981-85 and
      decreased thereafter in men. In women, maximum incidence occurred in 1986-90 and
      was followed by a decrease. Cryptococcosis was rare in the non-predisposed. Thus,
      cryptococcosis incidence increased markedly in men early in the AIDS epidemic,
      and began to decrease in both male and female HIV-positive patients well before
      highly active antiretroviral therapy became available.

PMID- 15743431
TI  - Molecular epidemiology of Candida species isolated from urine at an intensive
      care unit.
AB  - Candida spp. has been the leading microorganism isolated from the urine specimens
      of patients hospitalized at the Anesthesiology and Reanimation intensive care
      unit (ICU) of Dokuz Eylul University Hospital, Izmir, since 1998. This study was
      undertaken to investigate the clonal relationship of Candida urine isolates in
      order to find the mode of spread among the patients. Epidemiological surveillance
      of 38 Candida albicans, 15 Candida tropicalis and 12 Candida glabrata recovered
      from the urine specimens of patients who were hospitalized in the ICU between
      June 11, 2000 and October 15, 2001 was carried out by antifungal susceptibility
      testing and randomly amplified polymorphic DNA (RAPD) analysis. Two short primers
      [Cnd3 (5'-CCAGATGCAC-3') and Cnd4 (5'-ACGGTACACT-3')] were used for RAPD. None of
      the isolates had high minimal inhibitory concentration (MIC) values (>1 microg
      ml(-1)) against amphotericin B with MIC50 values of 0.5 microg ml(-1), 0.5 microg
      ml(-1) and 0.125 microg ml(-1) for C. albicans, C. tropicalis and C. glabrata
      isolates, respectively. However, three C. glabrata isolates were resistant and
      one C. albicans and five C. glabrata isolates were dose-dependent susceptible (D
      DS) to fluconazole. Among C. albicans isolates 19 and 20 patterns were detected
      with primers Cnd3 and Cnd4, respectively. When primers Cnd3 and Cnd4 were
      evaluated together, three and four genotypes were identified for C. tropicalis
      and C. glabrata isolates, respectively. Our results suggest that the source of C.
      albicans isolates was mostly endogenous. It is difficult to interpret the mode of
      spread of C. tropicalis and C. glabrata urine isolates as we obtained
      insufficient banding patterns for these species.

PMID- 15743432
TI  - Oral Candida species and betel quid-associated oral lesions in Padaung women of
      Northern Thailand.
AB  - Purpose of the present investigation was to study the association between the
      betel quid chewing (BQC) habits, the oral yeast flora and oral lesions in female
      Padaung of northern Thailand. Oral swabs were taken from the tongue and palate of
      50 Padaung women with and 50 control individuals without BQC habit. The spectrum
      of oral Candida species in both groups was determined microbiologically. In
      addition, oral mucosal lesions were registered in both groups. Mean age of BQ
      chewers was 35.4 years, of non-chewers was 19.2 years. Candida parapsilosis was
      the most common Candida spp. isolated both in BQ chewers (46%) and non-chewers
      (44%). Candida albicans was revealed in 24% of BQ chewers and 18% of non-chewers.
      There was no significant difference in carriage of Candida spp. isolated between
      both groups. Forty-four per cent of BQ chewers revealed betel chewers mucosa, 10%
      showed leukoedema. Isolated populations such as the Padaung may reveal different
      patterns of candidal flora, in this case a predominance of Candida parapsilosis.

PMID- 15743433
TI  - Prevalence of tinea capitis in Ethiopian schoolchildren.
AB  - The prevalence of dermatophytosis and the spectrum of dermatophyte species were
      determined in children attending two schools in Addis Ababa, Ethiopia.
      Demographic and clinico-dermatological data were collected. Specimens were taken
      for microscopy and culture from all suspected lesions. Dermatophyte species were
      identified by morphology and biochemical tests, supplemented by sequencing of the
      rDNA ITS 2 region in selected isolates. From the Biruh Tesfa Elementary School
      (BTES) 824 students, and from Mount Olive Academy (MOA) all 124 students, were
      included. In BTES 513 (62.3%) students were clinically diagnosed with
      dermatophytosis, 463 (90.3 %) of them with tinea capitis. In 200 consecutive
      samples from BTES, and in 66 from MOA, 75 and 62%, respectively, contained fungal
      elements at microscopy. From BTES, 163/496 (33%) samples were culture-positive,
      of which 149 (91.4%) grew with dark purple colonies identified as Trichophyton
      violaceum, while 244 (49.4%) samples were contaminated. A few strains grew slowly
      developing white to cream colonies, two were identified as T. verrucosum, and 12
      as white T. violaceum. From MOA 44 (66.7%) of samples were culture-positive, 38
      (87%) were identified as T. violaceum, and one (2.3%) as T. verrucosum, while 33%
      showed no growth. Four white isolates of T.violaceum were confirmed by DNA
      sequencing. Dermatophytosis was thus diagnosed in 55-62% of children screened at
      two schools of different socioeconomic standards in the Ethiopian capital.
      Trichophyton violaceum constituted 87-90% of all isolates. White variants of T.
      violaceum were diagnosed in 16 cases.

PMID- 15743434
TI  - Intestinal prevalence of the neurotropic black yeast Exophiala (Wangiella)
      dermatitidis in healthy and impaired individuals.
AB  - A screening of 2300 samples of faeces from humans with and without underlying
      disease revealed that the black yeast Exophiala dermatitidis is present at a
      frequency of 5.2 per thousand (n=12). Eight individuals positive for the fungus
      had diarrhoea at the moment of its isolation, out of 11 where relevant
      information was available. Judging from repeated isolation over several weeks in
      one patient, the organism is able to persist in the human intestinal tract.

PMID- 15743436
TI  - Staffing, ratios and skill mix--is there an Australian story?

PMID- 15743435
TI  - Efficacy of caspofungin in prophylaxis and treatment of an adult leukemic patient
      with invasive pulmonary aspergillosis in allogeneic stem cell transplantation.
AB  - Summary Invasive aspergillosis is a major problem in the management of
      immunocompromised patients, its prevalence is rising and it is still a major
      cause of death in this group. The clinical success rate with classical drugs is
      far away from expectations. New drugs are needed in the treatment of this
      complication. Belonging to the new class of echinocandins, caspofungin is a newly
      introduced and promising drug in this fatal situation. We report a patient with
      acute myeloid leukemia who had invasive pulmonary aspergillosis during induction
      therapy being treated with amphotericin B in first step and afterwards with
      caspofungin. The patient received consolidation therapy and allogeneic stem cell
      transplantation while using caspofungin, and did not experience any adverse
      effect related to drug. Many side effects, e.g. derangements in liver and kidney
      functions, hypokalemia, infusion-related side effects and especially
      thrombocytopenia, which are common with amphotericin B treatment are no longer
      problem with caspofungin. The efficacy of caspofungin in terms of regression of
      pulmonary lesions and control of fever is quite successful. The optimal therapies
      for opportunistic fungal infections are still debated, and further evaluation is
      needed.

PMID- 15743437
TI  - Rethinking theatre in modern operating rooms.
AB  - Metaphor is a means through which a widely accepted meaning of a word is used in
      a different context to add understanding that would otherwise be difficult to
      conceive. Through etymological and metaphorical associations, we contend that
      aspects of "theatre" are still relevant in the modern operating rooms and that
      the use of dramaturgical metaphors can add another layer of understanding about
      the social reality in this setting. We begin by exploring the historical roots
      and derivation of the word theatre as it applied to anatomical dissection and
      surgery. Briefly, we touch on the work of Erving Goffman and examine how his work
      has been used by others to explore aspects of operating room nursing. Then,
      drawing on data from a postmodern ethnographic study that has been used to
      examine communication in operating room nursing, four dramaturgical metaphors are
      used to illustrate the argument. They are drama, the script and learning the
      lines, the show must go on, and changing between back stage and front stage. To
      conclude, the small amount of previously published literature on this topic is
      compared and contrasted, and the relevance of using dramaturgical metaphors to
      understand modern operating rooms is discussed. Being able to distinguish between
      the inherent drama in operating room work and the dramatic realisation of
      individuals who work within, can help operating room nurses to think differently
      about, and perhaps re-evaluate their social situation and how they function
      within it.

PMID- 15743438
TI  - The anatomy of a forbidden desire: men, penetration and semen exchange.
AB  - The rising popularity of unprotected anal sex (bareback sex) among men who have
      sex with men (MSM) is perplexing healthcare providers working in sexual health
      clinics. Epidemiological research on the topic overlooks several socio-cultural
      and psychological dimensions. Our research attempts to construct an appropriate
      theoretical edifice by which we can understand this sexual practice. In order to
      achieve this objective, a qualitative design was selected and 18 semiconductive
      in-depth interviews were carried out with barebackers from five European and
      North American cities. We then analyzed the data using two theoretical approaches
      that were sensitive to the issues of desire, transgression and pleasure. These
      theories are those of the late French psychoanalyst, Jacques Lacan, and those of
      poststructural thinkers, Gilles Deleuze and Felix Guattari. These theoretical
      frameworks helped shed light on the significance of bareback sex, and can
      potentially influence healthcare providers in gaining a better understanding not
      only of their clients, but also of their own role in the circuitry of desire at
      work within bareback. We found that while the exchange of semen constitutes a
      dangerous and irrational practice to healthcare professionals, it is nevertheless
      a significant variable in the sexual lives of barebackers that needs to be taken
      into consideration in the provision of healthcare services.

PMID- 15743439
TI  - Regulating hospital use: length of stay, beds and whiteboards.
AB  - This paper presents part of a larger study of contemporary nursing practice and
      the rationalisation of hospital length of stay. Informed by Michel Foucault's
      work on governmentality, length of hospital stay and the re-engineering of
      surgical services are examined, not in terms of numerical representations of
      hospital use, but as part of social and political processes through which certain
      concepts are made susceptible to measurement and practices are organised. Using
      data generated through fieldwork in a hospital surgical division this analysis
      offers understandings of how social practices around length of hospital stay are
      translated and how they pattern contemporary hospital nursing practice. Nursing
      practice is explored through the reconstitution of hospital beds and the demands
      of local administration of hospital length of stay.

PMID- 15743440
TI  - Nursing scholars appropriating new methods: the use of discourse analysis in
      scholarly nursing journals 1996-2003.
AB  - Nursing scholars appropriate the analysis of discourse. "Discourse analysis"
      covers a wide spectrum of approaches to analysing meaning and language and there
      is no widely accepted definition of either a concept or an analysis of discourse.
      A sample of the discourse analyses indexed in the CINAHL database was analysed in
      order to identify what notions of discourse and discourse analysis are preferred
      by nursing scholars. The results showed that nursing scholars prefer approaches
      to discourse that resemble mainstream qualitative research avoiding social life
      and interaction. Explanations for these findings are briefly outlined.

PMID- 15743441
TI  - Dwelling with stories that haunt us: building a meaningful nursing practice.
AB  - The purpose of this article is to reflect on pediatric critical care nurses'
      experience of grief by focusing on the meaning of the stories that haunt them. It
      is suggested that these stories are the nurses' attempt to find ways to journey
      through their grief and to live with the mystery of life and death. It is also
      the task of these stories to throw light on their experiences, a task that is
      never entirely finished. Dwelling with the stories that haunt them helps to
      provide nurses with a moral structure of critical care nursing practice. Their
      reflections upon the meaning of their experiences of grief can lead to a view of
      death that is not always perceived as an evil to flee, but is upheld as a source
      of value and revelation as critical care nurses strive to build who they are and
      how they practice the art of nursing.

PMID- 15743442
TI  - Recovery from depression: a discourse analysis of interpersonal psychotherapy.
AB  - This paper describes a discourse analysis of the process of interpersonal
      psychotherapy (IPT) in the recovery from depression. It demonstrates how IPT is
      an effective treatment strategy for mental health nurses to utilise in the
      treatment of depression. The discourse analysis highlights how the development of
      more meaningful subject positions enables one woman to recover from her
      depression. The process of recovery is underpinned by an understanding of women's
      depression as promoted by contemporary social and cultural expectations for
      detachment and reflexivity. This paper shows how IPT provides an opportunity for
      recovery from depression for one woman by facilitating a reconstruction of her
      subject positions in relation to others. The discourse analysis revealed that the
      therapist facilitated this through the use of a range of techniques: seeking
      information, exploring beliefs/values/assumptions, exploring communication
      patterns, exploring affective responses and exploring alternative subject
      positions.

PMID- 15743443
TI  - Sustaining self: moving beyond the unexpected realities of teaching in practice.
AB  - Nurse educators who teach undergraduate students in clinical practice frequently
      encounter, or are thrown into situations that interrupt smooth activity, pausing
      to make sense of what is going on in order to respond in a manner that is
      consistent with their professional beliefs and values. In moving towards, within
      and beyond this interruption in smooth activity, identified within this research
      as an Unready-to-Hand immersion, these educators create a matrix of situational
      knowing and wisdom that surrounds propositional knowing. In striving to clarify
      the knowing that informs the clinical nurse educator's response to unexpected
      situations, I referred to philosophical literature on tacit knowledge, practice
      wisdom, smooth activity and the Unready-to-Hand mode of engagement. I carried out
      an interpretive research project involving reflections on personal experiences
      followed by two layers of interviewing with nurse educators teaching students in
      practice. The first layer of individual interviews was with eight nurse educators
      who in their role experienced Unready-to-Hand immersions. The second layer
      involved of three of these eight participants who chose to continue with more in
      depth, unstructured interviews. One participant not involved in the original set
      of interviews approached me individually and asked to participate in the in-depth
      interviews, which they did. An interpretive analysis of these nurse educators'
      stories illuminated Unready-to-Hand as Adventure, highlighting the elements of
      attuning to difference, the domains of practice within Unready-to-Hand and three
      modes of unknowing. This paper focuses on one of the domains of practice:
      sustaining self.

PMID- 15743445
TI  - The stability of the Arabidopsis transcriptome in transgenic plants expressing
      the marker genes nptII and uidA.
AB  - The ATH1 Arabidopsis GeneChip from Affymetrix was used to search for
      transcriptome changes in Arabidopsis associated with the strong expression of
      transgenes regulated by constitutive promoters. The insertion and expression of
      the commonly used marker genes, uidA and nptII, did not induce changes to the
      expression patterns of the approximately 24 000 genes that were screened under
      optimal growth conditions and under physiological stress imposed by low
      temperatures. Approximately 8000 genes (35% of the Arabidopsis genome) underwent
      changes in gene expression in both wild-type and transgenic plants under abiotic
      stresses such as salt, dehydration, cold, and heat. This study provides detailed
      information on the extent of non-targeted or pleiotropic effects of transgenes on
      plants and shows that the transgenic and non-transgenic plants were equivalent in
      their global patterns of transcription. This information may help to extend our
      understanding and interpretation of the principle of substantial equivalence
      which is used as a first step in the biosafety evaluation of transgenic crops.

PMID- 15743446
TI  - The conserved Xanthomonas campestris pv. vesicatoria effector protein XopX is a
      virulence factor and suppresses host defense in Nicotiana benthamiana.
AB  - Nicotiana benthamiana leaves display a visible plant cell death response when
      infiltrated with a high titer inoculum of the non-host pathogen, Xanthomonas
      campestris pv. vesicatoria (Xcv). This visual phenotype was used to identify
      overlapping cosmid clones from a genomic cosmid library constructed from the Xcv
      strain, GM98-38. Individual cosmid clones from the Xcv library were conjugated
      into X. campestris pv. campestris (Xcc) and exconjugants were scored for an
      altered visual high titer inoculation response in N. benthamiana. The molecular
      characterization of the cosmid clones revealed that they contained a novel gene,
      xopX, that encodes a 74-kDa type III secretion system (TTSS) effector protein.
      Agrobacterium-mediated transient expression of XopX in N. benthamiana did not
      elicit the plant cell death response although detectable XopX protein was
      produced. Interestingly, the plant cell death response occurred when the xopX
      Agrobacterium-mediated transient expression construct was co-inoculated with
      strains of either XcvDeltaxopX or Xcc, both lacking xopX. The co-inoculation
      complementation of the plant cell death response also depends on whether the
      Xanthomonas strains contain an active TTSS. Transgenic 35S-xopX-expressing N.
      benthamiana plants also have the visible plant cell death response when
      inoculated with the non-xopX-expressing strains XcvDeltaxopX and Xcc.
      Unexpectedly, transgenic 35S-xopX N. benthamiana plants displayed enhanced
      susceptibility to bacterial growth of Xcc as well as other non-xopX-expressing
      Xanthomonas and Pseudomonas strains. This result is also consistent with the
      increase in bacterial growth on wild type N. benthamiana plants observed for Xcc
      when XopX is expressed in trans. Furthermore, XopX contributes to the virulence
      of Xcv on host pepper (Capsicum annuum) and tomato (Lycopersicum esculentum)
      plants. We propose that the XopX bacterial effector protein targets basic innate
      immunity in plants, resulting in enhanced plant disease susceptibility.

PMID- 15743447
TI  - Arabidopsis mutants Atisa1 and Atisa2 have identical phenotypes and lack the same
      multimeric isoamylase, which influences the branch point distribution of
      amylopectin during starch synthesis.
AB  - The aim of this work was to evaluate the function of isoamylase in starch granule
      biosynthesis in Arabidopsis leaves. A reverse-genetic approach was used to
      knockout AtISA1, one of three genes in Arabidopsis encoding isoamylase-type
      debranching enzymes. The mutant (Atisa1-1) lacks functional AtISA1 transcript and
      the major isoamylase activity (detected by native gels) in crude extracts of
      leaves. The same activity is abolished by mutation at the DBE1 locus, which
      encodes a second isoamylase-type protein, AtISA2. This is consistent with the
      idea that ISA1 and ISA2 proteins are subunits of the same enzyme in vivo. Atisa1
      1, Atisa2-1 (dbe1), and the Atisa1-1/Atisa2-1 double mutant all have identical
      phenotypes. Starch content is reduced compared with the wild type but substantial
      quantities of the soluble glucan phytoglycogen are produced. The amylopectin of
      the remaining starch and the phytoglycogen in the mutants are structurally
      related to each other and differ from wild-type amylopectin. Electron micrographs
      reveal that the phytoglycogen-accumulating phenotype is highly tissue-specific.
      Phytoglycogen accumulates primarily in the plastids of the palisade and spongy
      mesophyll cells. Remarkably, other cell types appear to accumulate only starch,
      which is normal in appearance but is altered in structure. As phytoglycogen
      accumulates during the day, its rate of accumulation decreases, its structure
      changes and intermediates of glucan breakdown accumulate, suggesting that
      degradation occurs simultaneously with synthesis. We conclude that the
      AtISA1/AtISA2 isoamylase influences glucan branching pattern, but that this may
      not be the primary determinant of partitioning between crystalline starch and
      soluble phytoglycogen.

PMID- 15743448
TI  - Senescence-associated vacuoles with intense proteolytic activity develop in
      leaves of Arabidopsis and soybean.
AB  - Vacuolar compartments associated with leaf senescence and the subcellular
      localization of the senescence-specific cysteine-protease SAG12 (senescence
      associated gene 12) were studied using specific fluorescent markers, the
      expression of reporter genes, and the analysis of high-pressure frozen/freeze
      substituted samples. Senescence-associated vacuoles (SAVs) with intense
      proteolytic activity develop in the peripheral cytoplasm of mesophyll and guard
      cells in Arabidopsis and soybean. The vacuolar identity of these compartments was
      confirmed by immunolabeling with specific antibody markers. SAVs and the central
      vacuole differ in their acidity and tonoplast composition: SAVs are more acidic
      than the central vacuole and, whereas the tonoplast of central vacuoles is highly
      enriched in gamma-TIP (tonoplast intrinsic protein), the tonoplast of SAVs lacks
      this aquaporin. The expression of a SAG12-GFP fusion protein in transgenic
      Arabidopsis plants shows that SAG12 localizes to SAVs. The analysis of
      Pro(SAG12):GUS transgenic plants indicates that SAG12 expression in senescing
      leaves is restricted to SAV-containing cells, for example, mesophyll and guard
      cells. A homozygous sag12 Arabidopsis mutant develops SAVs and does not show any
      visually detectable phenotypical alteration during senescence, indicating that
      SAG12 is not required either for SAV formation or for progression of visual
      symptoms of senescence. The presence of two types of vacuoles in senescing leaves
      could provide different lytic compartments for the dismantling of specific
      cellular components. The possible origin and functions of SAVs during leaf
      senescence are discussed.

PMID- 15743449
TI  - Silencing the nuclear actin-related protein AtARP4 in Arabidopsis has multiple
      effects on plant development, including early flowering and delayed floral
      senescence.
AB  - Actin-related proteins (ARPs) share moderate sequence homology and basal
      structure with conventional actins and are found in all eukaryotes. While the
      functions of most of the divergent ARPs are not clear, several of them are
      localized to the nucleus and have been identified as components of various
      chromatin-modifying complexes. Using an antibody to Arabidopsis AtARP4, we found
      this conserved homolog of human BAF53 and yeast Arp4 is concentrated in the
      nucleoplasm of Arabidopsis, Brassica, and tobacco cells. To gain further insight
      into the role of ARP4, we have examined Arabidopsis plants that are defective in
      AtARP4 expression. Phenotypic analysis of the arp4-1 mutant allele, which has a T
      DNA insertion in the promoter region and a moderate reduction in the level of
      AtARP4 protein expression, revealed partial sterility due to defects in anther
      development. Targeting the distinct, 3' UTR of AtARP4 transcripts with RNA
      interference caused a drastic reduction in the level of AtARP4 protein expression
      in several independent transgenic lines, and resulted in strong pleiotropic
      phenotypes such as altered organization of plant organs, early flowering, delayed
      flower senescence and high levels of sterility. Western blot analysis and
      immunolabeling demonstrated a clear correlation between reductions in the level
      of AtARP4 expression and severity of the phenotypes. Based on our results and
      data on the orthologs of AtARP4 in yeast and other organisms, we suggest that
      AtARP4 is likely to exert its effects on plant development through the modulation
      of chromatin structure and subsequent changes in gene regulation.

PMID- 15743450
TI  - Mutations in Arabidopsis acyl-CoA oxidase genes reveal distinct and overlapping
      roles in beta-oxidation.
AB  - Indole-3-butyric acid (IBA) is an endogenous auxin used to enhance rooting during
      propagation. To better understand the role of IBA, we isolated Arabidopsis IBA
      response (ibr) mutants that display enhanced root elongation on inhibitory IBA
      concentrations but maintain wild-type responses to indole-3-acetic acid, the
      principle active auxin. A subset of ibr mutants remains sensitive to the
      stimulatory effects of IBA on lateral root initiation. These mutants are not
      sucrose dependent during early seedling development, indicating that peroxisomal
      beta-oxidation of seed storage fatty acids is occurring. We used positional
      cloning to determine that one mutant is defective in ACX1 and two are defective
      in ACX3, two of the six Arabidopsis fatty acyl-CoA oxidase (ACX) genes.
      Characterization of T-DNA insertion mutants defective in the other ACX genes
      revealed reduced IBA responses in a third gene, ACX4. Activity assays
      demonstrated that mutants defective in ACX1, ACX3, or ACX4 have reduced fatty
      acyl-CoA oxidase activity on specific substrates. Moreover, acx1 acx2 double
      mutants display enhanced IBA resistance and are sucrose dependent during seedling
      development, whereas acx1 acx3 and acx1 acx5 double mutants display enhanced IBA
      resistance but remain sucrose independent. The inability of ACX1, ACX3, and ACX4
      to fully compensate for one another in IBA-mediated root elongation inhibition
      and the ability of ACX2 and ACX5 to contribute to IBA response suggests that IBA
      response defects in acx mutants may reflect indirect blocks in peroxisomal
      metabolism and IBA beta-oxidation, rather than direct enzymatic activity of ACX
      isozymes on IBA-CoA.

PMID- 15743451
TI  - Genomics-based selection and functional characterization of triterpene
      glycosyltransferases from the model legume Medicago truncatula.
AB  - The biosynthesis of triterpene saponins is poorly characterized in spite of the
      importance of these glycosylated secondary metabolites for plant defense and
      animal health. The model legume Medicago truncatula synthesizes more than 30
      different saponins based on at least five triterpene aglycones; soyasapogenols B
      and E, medicagenic acid, hederagenin and bayogenin. We have employed an inducible
      cell culture system, DNA array-based and in silico transcript profiling, and
      targeted metabolite profiling, to identify triterpene glycosyltransferases (GTs)
      from among the more than 300 GTs expressed in M. truncatula. Two uridine
      diphosphate glucosyltransferases were functionally characterized; UGT73K1 with
      specificity for hederagenin and soyasapogenols B and E, and UGT71G1 with
      specificity for medicagenic acid. The latter enzyme also glycosylated certain
      isoflavones and the flavonol quercetin with higher efficiency than triterpenes;
      however, integrated transcript and metabolite profiling supported a function for
      UGT71G1 in terpenoid but not (iso)flavonoid biosynthesis in the elicited cell
      cultures.

PMID- 15743452
TI  - Endosomal proteases facilitate the fusion of endosomes with vacuoles at the final
      step of the endocytotic pathway.
AB  - The mechanism by which plasma membrane proteins are transported to vacuoles for
      degradation has not been well characterized in plants. To clarify how plasma
      membrane proteins are degraded, we monitored the endocytotic pathway in tobacco
      suspension-cultured BY-2 cells with a fluorescent endocytosis marker, FM4-64.
      Because of the efficient and rapid delivery of endosomes to the vacuoles,
      endosomes were scarcely detectable. Interestingly, we found that E-64d, an
      inhibitor of papain family proteases, caused the accumulation of a large number
      of endosomes in the cells under the sucrose-starved condition. This result
      indicates that E-64d attenuates the fusion of endosomes with vacuoles. We
      identified two papain homologues, which are localized in the endosomes, with a
      biotinylated inhibitor. We designated them as endosome-localized papains (ENPs).
      Immunofluorescent analysis revealed that vacuolar sorting receptor, a marker of
      prevacuolar compartment (PVC), was localized in the endosomes. This result and
      their acidic nature show that the endosomes correspond to PVC. These results
      suggest that ENPs facilitate the final step in the vacuolar trafficking pathway
      under the sucrose-starved condition. We further examined the effects of E-64d on
      two transgenic Arabidopsis plants that constitutively express a fusion protein
      composed of green fluorescent protein (GFP) and a plasma membrane protein (GFP
      PIP2a or GFP-LTI6b). GFP fluorescence was observed on the plasma membrane of root
      cells in these transgenic plants. Treatment with E-64d induced the accumulation
      of GFP-fluorescent endosomes and inhibited the degradation of these fusion
      proteins. No GFP fluorescence was observed in vacuoles in E-64d-treated
      transgenic plants. Taken together, these results suggest that endosomal proteases
      are required for the fusion of endosomes with vacuoles at the final step in the
      endocytotic pathway for degradation of plasma membrane proteins in plants.

PMID- 15743454
TI  - pOp6/LhGR: a stringently regulated and highly responsive dexamethasone-inducible
      gene expression system for tobacco.
AB  - We describe pOp/LhGR, a dexamethasone-inducible derivative of the pOp/LhG4
      transcription activation system, and its use in tobacco to regulate expression of
      uidA (encoding beta-glucuronidase; GUS) and the cytokinin-biosnythetic gene ipt.
      The pOp/LhGR system exhibited stringent regulation and strong induced phenotypes
      in soil and tissue culture. In conjunction with an improved target promoter,
      pOp6, that carries six copies of an optimized lac operator sequence the pOp6/LhGR
      system directed induced GUS activities that exceeded those obtained with pOp/LhG4
      or the CaMV 35S promoter but without increased uninduced activity. A single dose
      of dexamethasone was sufficient to direct cytotoxic levels of ipt expression in
      soil-grown plants although uninduced plants grew normally throughout a complete
      life cycle. In vitro, induced transcripts were detectable within an hour of
      dexamethasone application and 1 nM dexamethasone was sufficient for half maximal
      induction of GUS activity. Various methods of dexamethasone application were
      successfully applied under tissue culture and greenhouse conditions. We observed
      no inhibitory effects of dexamethasone or LhGR on plant development even with the
      highest concentrations of inducer, although tobacco seedlings were adversely
      affected by ethanol used as a solvent for dexamethasone stock solutions. The
      pOp/LhGR system provides a highly sensitive, efficient, and tightly regulated
      chemically inducible transgene expression system for tobacco plants.

PMID- 15743453
TI  - New pOp/LhG4 vectors for stringent glucocorticoid-dependent transgene expression
      in Arabidopsis.
AB  - To facilitate glucocorticoid-inducible transgene expression from the pOp promoter
      in Arabidopsis the ligand-binding domain of a rat glucocorticoid receptor (GR
      LBD) was fused to the amino terminus of the synthetic transcription factor LhG4
      to generate LhGR-N. Fusions bearing the GR LBD at other positions in LhG4
      exhibited incomplete repression or inefficient induction. LhGR-N was stringently
      repressed in the absence of exogenous glucocorticoid but was fully activated by
      addition of 2 microm dexamethasone which resulted in 1000-fold increase in GUS
      reporter activity. Half maximal induction was achieved with 0.2 microm
      dexamethasone. Reporter transcripts were detectable within 2 h of dexamethasone
      application and peaked 4-10 h later. Neither LhGR-N nor dexamethasone affected
      seedling development although ethanol retarded development when used as a solvent
      for dexamethasone. The efficiency of the pOp target promoter was improved 10- to
      20-fold by incorporating six copies of the ideal lac operator with sufficient
      inter-operator spacing to allow simultaneous occupancy. Introduction of the TMV
      Omega sequence into the 5'UTR resulted in a further 10-fold increase in
      dexamethasone-inducible reporter activity and an increase in the induction factor
      to 10(4). Although promoters containing the TMV Omega sequence exhibited slightly
      increased basal expression levels in the absence of dexamethasone, stringent
      regulation of the cytokinin biosynthetic gene ipt was achieved with all
      promoters. Despite the severity of the induced ipt phenotypes, transcripts for
      the KNOX homoeodomain transcription factors BREVIPEDICELLUS and SHOOTMERISTEMLESS
      were not significantly increased within 48 h of dexamethasone application to
      seedlings.

PMID- 15743456
TI  - Stable two-element control of dTph1 transposition in mutator strains of Petunia
      by an inactive ACT1 introgression from a wild species.
AB  - The high copy dTph1 transposon system of Petunia (Solanaceae) is one of the most
      powerful insertion mutagens in plants, but its activity cannot be controlled in
      the commonly used mutator strains. We analysed the regulation of dTph1 activity
      by QTL analysis in recombinant inbred lines of the mutator strain W138 and a wild
      species (P. integrifolia spp. inflata). Two genetic factors were identified that
      control dTph1 transposition. One corresponded to the ACT1 locus on chromosome I.
      A second, previously undescribed locus ACT2 mapped on chromosome V. As a 6-cM
      introgression in W138, the P. i. inflata act1(S6) allele behaved as a single
      recessive locus that fully eliminated transposition of all dTph1 elements in all
      stages of plant development and in a heritable fashion. Weak dTph1 activity was
      restored in act1S6/ACT2S6 double introgression lines, indicating that the P. i.
      inflata allele at ACT2 conferred a low level of transposition. Thus, the act1S6
      allele is useful for simple and predictable control of transposition of the
      entire dTph1 family when introgressed into an ultra-high copy W138 mutator
      strain. We demonstrate the use of the ACT1W138/act1S6 allele pair in a two
      element dTph1 transposition system by producing 10,000 unique and fixed dTph1
      insertions in a population of 1250 co-isogenic lines. This Petunia system
      produces the highest per plant insertion number of any known two-element system,
      providing a powerful and logistically simple tool for transposon mutagenesis of
      qualitative as well as quantitative traits.

PMID- 15743455
TI  - Large-scale screening of Arabidopsis enhancer-trap lines for seed germination
      associated genes.
AB  - Enhancer trap is a powerful approach for identifying tissue- and stage-specific
      gene expression in plants and animals. For Arabidopsis research, beta
      glucuronidase (GUS) enhancer-trap lines have been created and successfully used
      to identify tissue-specific gene expression in many plant organs. However,
      limited applications of these lines for seed germination research have been
      reported. This is probably due to the impermeability of the testa to the GUS
      substrate. By focusing on the stages between testa and endosperm rupture, we were
      able to circumvent the testa barrier to the GUS substrate and observe diverse
      tissue-specific gene expression during germination sensu stricto. One hundred and
      twenty-one positive subpools of 10 lines out of 1130 were isolated. Approximately
      4500 plants from these subpools were grown in a greenhouse and one to seven
      individual plants exhibiting GUS expression in seeds were isolated for each
      subpool. This library of the Arabidopsis seed enhancer-trap lines is an efficient
      tool for identifying seed germination-associated genes. The individual lines from
      this library will be provided to the international seed biology research
      community. International collaboration to identify the trapped genes using genome
      walking PCR and to characterize the gene functions using knockout plants will
      significantly enhance our understanding of the molecular mechanisms of seed
      germination.

PMID- 15743457
TI  - 21st European Workshop for Rheumatology Research, Vienna, Austria, 1-4 March
      2001. Abstracts.

PMID- 15743458
TI  - 24th Congress of the International Association for Breast Cancer Research.
      Advances in human breast cancer research: preclinical models. Sacramento, USA. 1
      5 November 2003. Abstracts.

PMID- 15743459
TI  - Autumn Scientific Meeting of the Association of Cardiothoracic Anaesthetists,
      Windermere, United Kingdom, 3 November 2000. Abstracts.

PMID- 15743460
TI  - 18th Spring Meeting of the Association of Cardiothoracic Anaesthetists,
      Cambridge, United Kingdom, 22 June 2001. Abstracts.

PMID- 15743461
TI  - 19th Spring Meeting of the Association of Cardiothoracic Anaesthetists.
      Cambridge, United Kingdom, 21 June 2002. Abstracts.

PMID- 15743462
TI  - Abstracts of the 4th International Symposium on the Pathophysiology of
      Cardiopulmonary Bypass: Endothelial damage. Munich, Germany, 29 November 2002.

PMID- 15743463
TI  - Abstracts of the 2nd International Symposium on Intensive Care and Emergency
      Medicine for Latin America. Sao Paulo, Brazil, 25-28 June 2003.

PMID- 15743464
TI  - Neural control of breathing. Rotorua, New Zealand, 1-4 September 2001. Abstracts
      of a meeting.

PMID- 15743465
TI  - A2B adenosine receptor activity is reduced in neutrophils from patients with
      systemic sclerosis.
AB  - We conducted the present study to investigate protein expression and functioning
      of A2A and A2B adenosine receptors (ARs) in neutrophils of patients affected by
      systemic sclerosis (SSc). The presence of A2A and A2B ARs was assessed by
      immunoblotting using specific antibodies. Equilibrium A2A and A2B ARs binding
      parameters were evaluated by radioligand binding assay. Functional studies were
      conducted to investigate coupling of the A2B AR to the adenylyl cyclase pathway.
      This is the first report of the use of Western blot analysis to confirm the
      presence of A2A and A2B ARs in human neutrophils. No significant changes in A2A
      AR binding parameters or expression levels were detected between SSc patients and
      healthy control individuals. A significant decrease (65%) in the maximum density
      of A2B AR binding sites occurred in SSc neutrophils, whereas no changes in the
      affinity constant values were found. Moreover, a decrease in A2B AR mediated
      adenylyl cyclase activity was observed in patients with SSc. Our findings
      demonstrate the occurrence of selective alterations in A2B AR density and
      signalling in SSc.

PMID- 15743466
TI  - Gene expression profiling in murine autoimmune arthritis during the initiation
      and progression of joint inflammation.
AB  - We present here an extensive study of differential gene expression in the
      initiation, acute and chronic phases of murine autoimmune arthritis with the use
      of high-density oligonucleotide arrays interrogating the entire mouse genome.
      Arthritis was induced in severe combined immunodeficient mice by using adoptive
      transfer of lymphocytes from proteoglycan-immunized arthritic BALB/c mice. In
      this unique system only proteoglycan-specific lymphocytes are transferred from
      arthritic mice into syngeneic immunodeficient recipients that lack adaptive
      immunity but have intact innate immunity on an identical (BALB/c) genetic
      background.Differential gene expression in response to donor lymphocytes that
      migrated into the joint can therefore be monitored in a precisely timed manner,
      even before the onset of inflammation. The initiation phase of adoptively
      transferred disease (several days before the onset of joint swelling) was
      characterized by differential expression of 37 genes, mostly related to
      chemokines, interferon-gamma and tumor necrosis factor-alpha signaling, and T
      cell functions. These were designated early arthritis 'signature' genes because
      they could distinguish between the naive and the pre-arthritic state. Acute joint
      inflammation was characterized by at least twofold overexpression of 256 genes
      and the downregulation of 21 genes, whereas in chronic arthritis a total of 418
      genes with an equal proportion of upregulated and downregulated transcripts were
      expressed differentially. Hierarchical clustering and functional classification
      of inflammation-related and arthritis-related genes indicated that the most
      common biological activities were represented by genes encoding interleukins,
      chemokine receptors and ligands, and by those involved in antigen recognition and
      processing.

PMID- 15743467
TI  - Microcirculation abnormalities in patients with fibromyalgia - measured by
      capillary microscopy and laser fluxmetry.
AB  - This unblinded preliminary case-control study was done to demonstrate functional
      and structural changes in the microcirculation of patients with primary
      fibromyalgia (FM). We studied 10 women (54.0 +/- 3.7 years of age) with FM
      diagnosed in accordance with the classification criteria of the American College
      of Rheumatology, and controls in three groups (n = 10 in each group) - age
      matched women who were healthy or who had rheumatoid arthritis or systemic
      scleroderma (SSc). All 40 subjects were tested within a 5-week period by the same
      investigators, using two noninvasive methods, laser fluxmetry and capillary
      microscopy. The FM patients were compared with the healthy controls (negative
      controls) and with rheumatoid arthritis patients and SSc patients (positive
      controls). FM patients had fewer capillaries in the nail fold (P < 0.001) and
      significantly more capillary dilatations (P < 0.05) and irregular formations (P <
      0.01) than the healthy controls. Interestingly, the peripheral blood flow in FM
      patients was much less (P < 0.001) than in healthy controls but did not differ
      from that of SSc patients (P = 0.73). The data suggest that functional
      disturbances of microcirculation are present in FM patients and that
      morphological abnormalities may also influence their microcirculation.

PMID- 15743468
TI  - Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5.
AB  - In patients with rheumatoid arthritis (RA), chemokine and chemokine receptor
      interactions play a central role in the recruitment of leukocytes into inflamed
      joints. This study was undertaken to characterize the expression of chemokine
      receptors in the synovial tissue of RA and non-RA patients. RA synovia (n = 8)
      were obtained from knee joint replacement operations and control non-RA synovia
      (n = 9) were obtained from arthroscopic knee biopsies sampled from patients with
      recent meniscal or articular cartilage damage or degeneration. The mRNA
      expression of chemokine receptors and their ligands was determined using gene
      microarrays and PCR. The protein expression of these genes was demonstrated by
      single-label and double-label immunohistochemistry. Microarray analysis showed
      the mRNA for CXCR5 to be more abundant in RA than non-RA synovial tissue, and of
      the chemokine receptors studied CXCR5 showed the greatest upregulation. PCR
      experiments confirmed the differential expression of CXCR5. By
      immunohistochemistry we were able to detect CXCR5 in all RA and non-RA samples.
      In the RA samples the presence of CXCR5 was observed on B cells and T cells in
      the infiltrates but also on macrophages and endothelial cells. In the non-RA
      samples the presence of CXCR5 was limited to macrophages and endothelial cells.
      CXCR5 expression in synovial fluid macrophages and peripheral blood monocytes
      from RA patients was confirmed by PCR. The present study shows that CXCR5 is
      upregulated in RA synovial tissue and is expressed in a variety of cell types.
      This receptor may be involved in the recruitment and positioning of B cells, T
      cells and monocytes/macrophages in the RA synovium. More importantly, the
      increased level of CXCR5, a homeostatic chemokine receptor, in the RA synovium
      suggests that non-inflammatory receptor-ligand pairs might play an important role
      in the pathogenesis of RA.

PMID- 15743469
TI  - Rheumatoid arthritis synovium contains plasmacytoid dendritic cells.
AB  - We have previously described enrichment of antigen-presenting HLA-DR+ nuclear
      RelB+ dendritic cells (DCs) in rheumatoid arthritis (RA) synovium. CD123+HLA-DR+
      plasmacytoid DCs (pDCs) and their precursors have been identified in human
      peripheral blood (PB), lymphoid tissue, and some inflamed tissues. We
      hypothesized recruitment of pDCs into the inflamed RA synovial environment and
      their contribution as antigen-presenting cells (APCs) and inflammatory cells in
      RA. CD11c+ myeloid DCs and CD123+ pDCs were compared in normal and RA PB,
      synovial fluid (SF), and synovial tissue by flow cytometry, immunohistochemistry,
      and electron microscopy and were sorted for functional studies. Nuclear RelB
      CD123+ DCs were located in perivascular regions of RA, in a similar frequency to
      nuclear RelB+CD123- DCs, but not normal synovial tissue sublining. Apart from
      higher expression of HLA-DR, the numbers and phenotypes of SF pDCs were similar
      to those of normal PB pDCs. While the APC function of PB pDCs was less efficient
      than that of PB myeloid DCs, RA SF pDCs efficiently activated resting allogeneic
      PB T cells, and high levels of IFN-gamma, IL-10, and tumor necrosis factor alpha
      were produced in response to incubation of allogeneic T cells with either type of
      SF DCs. Thus, pDCs are recruited to RA synovial tissue and comprise an APC
      population distinct from the previously described nuclear RelB+ synovial DCs.
      pDCs may contribute significantly to the local inflammatory environment.

PMID- 15743470
TI  - CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic
      arthritis.
AB  - The accumulation of T cells in the synovial membrane is the crucial step in the
      pathophysiology of the inflammatory processes characterizing juvenile idiopathic
      arthritis (JIA). In this study, we evaluated the expression and the pathogenetic
      role in oligoarticular JIA of a CXC chemokine involved in the directional
      migration of activated T cells, i.e. IFNgamma-inducible protein 10 (CXCL10) and
      its receptor, CXCR3. Immunochemistry with an antihuman CXCL10 showed that
      synovial macrophages, epithelial cells, and endothelial cells bear the chemokine.
      By flow cytometry and immunochemistry, it has been shown that CXCR3 is expressed
      at high density by virtually all T lymphocytes isolated from synovial fluid (SF)
      and infiltrating the synovial membrane. Particularly strongly stained CXCR3+ T
      cells can be observed close to the luminal space and in the perivascular area.
      Furthermore, densitometric analysis has revealed that the mRNA levels for CXCR3
      are significantly higher in JIA patients than in controls. T cells purified from
      SF exhibit a definite migratory capability in response to CXCL10. Furthermore, SF
      exerts significant chemotactic activity on the CXCR3+ T-cell line, and this
      activity is inhibited by the addition of an anti-CXCL10 neutralizing antibody.
      Taken together, these data suggest that CXCR3/CXCL10 interactions are involved in
      the pathophysiology of JIA-associated inflammatory processes, regulating both the
      activation of T cells and their recruitment into the inflamed synovium.

PMID- 15743471
TI  - Effect of adalimumab on neutrophil function in patients with rheumatoid
      arthritis.
AB  - Neutrophils are known to be targets for the biological activity of tumour
      necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA).
      Therefore, these cells may be among the targets of anti-TNF-alpha therapy. In
      this study we evaluated the effect of therapy with adalimumab (a fully human anti
      TNF-alpha mAb; dosage: 40 mg subcutaneously every other week) on certain
      phenotypic and functional aspects of neutrophils obtained from 10 selected
      patients with RA and 20 healthy control individuals. Peripheral blood neutrophils
      were obtained at baseline and during anti-TNF-alpha therapy (2, 6 and 12 weeks
      after the first administration of adalimumab). All patients had been receiving a
      stable regimen of hydroxychloroquine, methotrexate and prednisone for at least 3
      months before and during the study. Baseline neutrophil chemotaxis was
      significantly decreased in RA patients when compared with control individuals (P
      < 0.001). Two weeks after the first administration of adalimumab, chemotactic
      activity was completely restored, with no differences noted between patients and
      control individuals; these normal values were confirmed 6 and 12 weeks after the
      start of anti-TNF-alpha therapy. Phagocytic activity and CD11b membrane
      expression on neutrophils were similar between RA patients and control
      individuals; no modifications were observed during TNF-alpha neutralization. The
      production of reactive oxygen species, both in resting and PMA (phorbol 12
      myristate 13-acetate)-stimulated cells, was significantly higher in RA patients
      at baseline (P < 0.05) and was unmodified by anti-TNF-alpha mAb. Finally, we
      showed that the activation antigen CD69, which was absent on control neutrophils,
      was significantly expressed on neutrophils from RA patients at baseline (P <
      0.001, versus control individuals); however, the molecule was barely detectable
      on cells obtained from RA patients during adalimumab therapy. Because CD69
      potentially plays a role in the pathogenesis of arthritis, our findings suggest
      that neutrophils are among the targets of anti-TNF-alpha activity in RA and may
      provide an insight into a new and interesting mechanism of action of anti-TNF
      alpha mAbs in the control of inflammatory arthritis.

PMID- 15743472
TI  - Phenotypic and functional characterisation of CCR7+ and CCR7- CD4+ memory T cells
      homing to the joints in juvenile idiopathic arthritis.
AB  - The aim of the study was to characterise CCR7+ and CCR7- memory T cells
      infiltrating the inflamed joints of patients with juvenile idiopathic arthritis
      (JIA) and to investigate the functional and anatomical heterogeneity of these
      cell subsets in relation to the expression of the inflammatory chemokine
      receptors CXCR3 and CCR5. Memory T cells freshly isolated from the peripheral
      blood and synovial fluid (SF) of 25 patients with JIA were tested for the
      expression of CCR7, CCR5, CXCR3 and interferon-gamma by flow cytometry. The
      chemotactic activity of CD4 SF memory T cells from eight patients with JIA to
      inflammatory (CXCL11 and CCL3) and homeostatic (CCL19, CCL21) chemokines was also
      evaluated. Paired serum and SF samples from 28 patients with JIA were tested for
      CCL21 concentrations. CCR7, CXCR3, CCR5 and CCL21 expression in synovial tissue
      from six patients with JIA was investigated by immunohistochemistry. Enrichment
      of CD4+, CCR7- memory T cells was demonstrated in SF in comparison with paired
      blood from patients with JIA. SF CD4+CCR7- memory T cells were enriched for CCR5+
      and interferon-gamma+ cells, whereas CD4+CCR7+ memory T cells showed higher
      coexpression of CXCR3. Expression of CCL21 was detected in both SF and synovial
      membranes. SF CD4+ memory T cells displayed significant migration to both
      inflammatory and homeostatic chemokines. CCR7+ T cells were detected in the
      synovial tissue in either diffuse perivascular lymphocytic infiltrates or
      organised lymphoid aggregates. In synovial tissue, a large fraction of CCR7+
      cells co-localised with CXCR3, especially inside lymphoid aggregates, whereas
      CCR5+ cells were enriched in the sublining of the superficial subintima. In
      conclusion, CCR7 may have a role in the synovial recruitment of memory T cells in
      JIA, irrespective of the pattern of lymphoid organisation. Moreover, discrete
      patterns of chemokine receptor expression are detected in the synovial tissue.

PMID- 15743473
TI  - Inhibition of antithrombin by hyaluronic acid may be involved in the pathogenesis
      of rheumatoid arthritis.
AB  - Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis,
      proinflammatory processes, and proliferation of fibroblast-like cells.
      Abnormalities in these processes are primary features of rheumatoid arthritis
      (RA) in synovial tissues. Tissue destruction in joints causes the accumulation of
      large quantities of free hyaluronic acid (HA) in RA synovial fluid. The present
      study was conducted to investigate the effects of HA and several other
      glycosaminoglycans on antithrombin, a plasma inhibitor of thrombin. Various
      glycosaminoglycans, including HA, chondroitin sulfate, keratan sulfate, heparin,
      and heparan, were incubated with human antithrombin III in vitro. The residual
      activity of antithrombin was determined using a thrombin-specific chromogenic
      assay. HA concentrations ranging from 250 to 1000 mug/ml significantly blocked
      the ability of antithrombin to inhibit thrombin in the presence of Ca2+ or Fe3+,
      and chondroitin A, B and C also reduced this ability under the same conditions
      but to a lesser extent. Our study suggests that the high concentration of free HA
      in RA synovium may block antithrombin locally, thereby deregulating thrombin
      activity to drive the pathogenic process of RA under physiological conditions.
      The study also helps to explain why RA occurs and develops in joint tissue,
      because the inflamed RA synovium is uniquely rich in free HA along with
      extracellular matrix degeneration. Our findings are consistent with those of
      others regarding increased coagulation activity in RA synovium.

PMID- 15743474
TI  - Repression of anti-proliferative factor Tob1 in osteoarthritic cartilage.
AB  - Osteoarthritis is the most common degenerative disorder of the modern world.
      However, many basic cellular features and molecular processes of the disease are
      poorly understood. In the present study we used oligonucleotide-based microarray
      analysis of genes of known or assumed relevance to the cellular phenotype to
      screen for relevant differences in gene expression between normal and
      osteoarthritic chondrocytes. Custom made oligonucleotide DNA arrays were used to
      screen for differentially expressed genes in normal (n = 9) and osteoarthritic (n
      = 10) cartilage samples. Real-time polymerase chain reaction (PCR) with gene
      specific primers was used for quantification. Primary human adult articular
      chondrocytes and chondrosarcoma cell line HCS-2/8 were used to study changes in
      gene expression levels after stimulation with interleukin-1beta and bone
      morphogenetic protein, as well as the dependence on cell differentiation. In situ
      hybridization with a gene-specific probe was applied to detect mRNA expression
      levels in fetal growth plate cartilage. Overall, more than 200 significantly
      regulated genes were detected between normal and osteoarthritic cartilage (P <
      0.01). One of the significantly repressed genes, Tob1, encodes a protein
      belonging to a family involved in silencing cells in terms of proliferation and
      functional activity. The repression of Tob1 was confirmed by quantitative PCR and
      correlated to markers of chondrocyte activity and proliferation in vivo. Tob1
      expression was also detected at a decreased level in isolated chondrocytes and in
      the chondrosarcoma cell line HCS-2/8. Again, in these cells it was negatively
      correlated with proliferative activity and positively with cellular
      differentiation. Altogether, the downregulation of the expression of Tob1 in
      osteoarthritic chondrocytes might be an important aspect of the cellular
      processes taking place during osteoarthritic cartilage degeneration. Activation,
      the reinitiation of proliferative activity and the loss of a stable phenotype are
      three major changes in osteoarthritic chondrocytes that are highly significantly
      correlated with the repression of Tob1 expression.

PMID- 15743476
TI  - The role of regulatory T cells in antigen-induced arthritis: aggravation of
      arthritis after depletion and amelioration after transfer of CD4+CD25+ T cells.
AB  - It is now generally accepted that CD4+CD25+ Treg cells play a major role in the
      prevention of autoimmunity and pathological immune responses. Their involvement
      in the pathogenesis of chronic arthritis is controversial, however, and so we
      examined their role in experimental antigen-induced arthritis in mice. Depletion
      of CD25-expressing cells in immunized animals before arthritis induction led to
      increased cellular and humoral immune responses to the inducing antigen
      (methylated bovine serum albumin; mBSA) and autoantigens, and to an exacerbation
      of arthritis, as indicated by clinical (knee joint swelling) and histological
      scores. Transfer of CD4+CD25+ cells into immunized mice at the time of induction
      of antigen-induced arthritis decreased the severity of disease but was not able
      to cure established arthritis. No significant changes in mBSA-specific immune
      responses were detected. In vivo migration studies showed a preferential
      accumulation of CD4+CD25+ cells in the inflamed joint as compared with CD4+CD25-
      cells. These data imply a significant role for CD4+CD25+ Treg cells in the
      control of chronic arthritis. However, transferred Treg cells appear to be unable
      to counteract established acute or chronic inflammation. This is of considerable
      importance for the timing of Treg cell transfer in potential therapeutic
      applications.

PMID- 15743475
TI  - Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a
      family-based case-control study.
AB  - Juvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic
      inflammatory disorders that primarily affect joints and can cause long-term
      disability. JRA is likely to be a complex genetic trait, or a series of such
      traits, with both genetic and environmental factors contributing to the risk for
      developing the disease and to its progression. The HLA region on the short arm of
      chromosome 6 has been intensively evaluated for genetic contributors to JRA, and
      multiple associations, and more recently linkage, has been detected. Other genes
      involved in innate and acquired immunity also map to near the HLA cluster on 6p,
      and it is possible that variation within these genes also confers risk for
      developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic
      reticulum chaperone that is involved in antigen processing, to elucidate its
      involvement, if any, in JRA. We employed both a case-control approach and the
      transmission disequilibrium test, and found linkage and association between the
      TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA
      cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati
      Children's Hospital Medical Center (82 simplex families) and one collected by the
      British Paediatric Rheumatology Group in London, England (74 simplex families).
      The transmission disequilibrium test for these cohorts combined was statistically
      significant (chi2 = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium
      testing between the HLA alleles that are known to be associated with systemic
      onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in
      the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals.
      These results suggest that there is a weak association between systemic onset JRA
      and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet
      unknown susceptibility allele in the centromeric part of chromosome 6.

PMID- 15743477
TI  - Autoantibodies specific for apoptotic U1-70K are superior serological markers for
      mixed connective tissue disease.
AB  - Modifications occurring on autoantigens during cell death have been proposed to
      have a role in the initiation of autoimmune diseases. Patients suffering from
      mixed connective tissue disease (MCTD) produce autoantibodies directed to U1
      small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein
      component, the U1-70K (70K) protein, are the most prominent. During apoptosis,
      70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with
      the complex. Autoantibodies preferentially recognizing the apoptotic form of 70K
      have been described previously, and an apoptosis-specific epitope on 70K has been
      identified. This study shows that 29 of 53 (54%) MCTD sera preferentially
      recognize the apoptotic form of 70K over intact 70K. Moreover, we show that
      antibodies directed to an apoptosis-specific epitope on 70K are more specifically
      associated with MCTD than other anti-70K antibodies, suggesting that apoptotic
      70K is a better antigen for the detection of these antibodies in MCTD patients.
      Longitudinal analysis of 12 MCTD patients showed in several patients that early
      sera are relatively enriched with antibodies recognizing an apoptosis-specific
      epitope, and that the levels of these apoptosis-specific antibodies decrease in
      time. These findings indicate that the early detection of apoptotic 70K is of
      considerable interest for anti-U1 snRNP-positive patients.

PMID- 15743478
TI  - Arthritis imaging using a near-infrared fluorescence folate-targeted probe.
AB  - A recently developed near-infrared fluorescence-labeled folate probe (NIR2
      folate) was tested for in vivo imaging of arthritis using a lipopolysaccharide
      intra-articular injection model and a KRN transgenic mice serum induction mouse
      model. In the lipopolysaccharide injection model, the fluorescence signal
      intensity of NIR2-folate (n = 12) and of free NIR2 (n = 5) was compared between
      lipopolysaccharide-treated and control joints. The fluorescence signal intensity
      of the NIR2-folate probe at the inflammatory joints was found to be significantly
      higher than the control normal joints (up to 2.3-fold, P < 0.001). The NIR2-free
      dye injection group showed a persistent lower enhancement ratio than the NIR2
      folate probe injection group. Excessive folic acid was also given to demonstrate
      a competitive effect with the NIR2-folate. In the KRN serum transfer model (n =
      4), NIR2-folate was applied at different time points after serum transfer, and
      the inflamed joints could be detected as early as 30 hours after arthritogenic
      antibody transfer (1.8-fold increase in signal intensity). Fluorescence
      microscopy, histology, and immunohistochemistry validated the optical imaging
      results. We conclude that in vivo arthritis detection was feasible using a folate
      targeted near-infrared fluorescence probe. This receptor-targeted imaging method
      may facilitate improved arthritis diagnosis and early assessment of the disease
      progress by providing an in vivo characterization of active macrophage status in
      inflammatory joint diseases.

PMID- 15743479
TI  - High-resolution optical coherence tomographic imaging of osteoarthritic cartilage
      during open knee surgery.
AB  - This study demonstrates the first real-time imaging in vivo of human cartilage in
      normal and osteoarthritic knee joints at a resolution of micrometers, using
      optical coherence tomography (OCT). This recently developed high-resolution
      imaging technology is analogous to B-mode ultrasound except that it uses infrared
      light rather than sound. Real-time imaging with 11-microm resolution at four
      frames per second was performed on six patients using a portable OCT system with
      a handheld imaging probe during open knee surgery. Tissue registration was
      achieved by marking sites before imaging, and then histologic processing was
      performed. Structural changes including cartilage thinning, fissures, and
      fibrillations were observed at a resolution substantially higher than is achieved
      with any current clinical imaging technology. The structural features detected
      with OCT were evident in the corresponding histology. In addition to changes in
      architectural morphology, changes in the birefringent or the polarization
      properties of the articular cartilage were observed with OCT, suggesting collagen
      disorganization, an early indicator of osteoarthritis. Furthermore, this study
      supports the hypothesis that polarization-sensitive OCT may allow osteoarthritis
      to be diagnosed before cartilage thinning. This study illustrates that OCT, which
      can eventually be developed for use in offices or through an arthroscope, has
      considerable potential for assessing early osteoarthritic cartilage and
      monitoring therapeutic effects for cartilage repair with resolution in real time
      on a scale of micrometers.

PMID- 15743480
TI  - Endothelin-1 in osteoarthritic chondrocytes triggers nitric oxide production and
      upregulates collagenase production.
AB  - The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1
      production and MMP-13 production was investigated in human osteoarthritis
      chondrocytes. The cells were isolated from human articular cartilage obtained at
      surgery and were cultured in the absence or presence of ET-1 with or without
      inhibitors of protein kinase or LY83583 (an inhibitor of soluble guanylate
      cyclase and of cGMP). MMP-1, MMP-13 and NO levels were then measured by ELISA and
      Griess reaction, respectively. Additionally, inducible nitric oxide synthase
      (iNOS) and phosphorylated forms of p38 mitogen-activated protein kinase, p44/42,
      stress-activated protein kinase/Jun-N-terminal kinase and serine-threonine Akt
      kinase were determined by western blot. Results show that ET-1 greatly increased
      MMP-1 and MMP-13 production, iNOS expression and NO release. LY83583 decreased
      the production of both metalloproteases below basal levels, whereas the inhibitor
      of p38 kinase, SB202190, suppressed ET-1-stimulated production only. Similarly,
      the ET-1-induced NO production was partially suppressed by the p38 kinase
      inhibitor and was completely suppressed by the protein kinase A kinase inhibitor
      KT5720 and by LY83583, suggesting the involvement of these enzymes in relevant ET
      1 signalling pathways. In human osteoarthritis chondrocytes, ET-1 controls the
      production of MMP-1 and MMP-13. ET-1 also induces NO release via iNOS induction.
      ET-1 and NO should thus become important target molecules for future therapies
      aimed at stopping cartilage destruction.

PMID- 15743482
TI  - Multilevel examination of minor salivary gland biopsy for Sjogren's syndrome
      significantly improves diagnostic performance of AECG classification criteria.
AB  - The recently observed low reproducibility of focus score (FS) assessment at
      different section depths in a series of single minor salivary gland biopsies
      highlighted the need for a standardized protocol of extensive histopathological
      examination of such biopsies in Sjogren's syndrome. For this purpose, a
      cumulative focus score (cFS) was evaluated on three slides cut at 200-mum
      intervals from each of a series of 120 salivary biopsies. The cFS was substituted
      for the baseline FS in the American-European Consensus Group (AECG) criteria set
      for Sjogren's syndrome classification, and then test specificity and sensitivity
      were assessed against clinical patient re-evaluation. Test performances of the
      AECG classification with the original FS and the score obtained after multilevel
      examination were statistically compared using receiver operating characteristic
      (ROC) curve analysis. The diagnostic performance of AECG classification
      significantly improved when the cFS was entered in the AECG classification; the
      improvement was mostly due to increased specificity in biopsies with a baseline
      FS >or= 1 but <2. The assessment of a cFS obtained at three different section
      levels on minor salivary gland biopsies can be useful especially in biopsies with
      baseline FSs between 1 and 2.

PMID- 15743481
TI  - Prescription channeling of COX-2 inhibitors and traditional nonselective
      nonsteroidal anti-inflammatory drugs: a population-based case-control study.
AB  - This pharmacoepidemiologic study was conducted to determine whether risk factors
      for upper gastrointestinal bleeding influenced the prescription of cyclo
      oxygenase (COX)-2 inhibitors and traditional nonselective nonsteroidal anti
      inflammatory drugs (NSAIDs) at the time when COX-2 inhibitors were first included
      in the formulary of reimbursed medications. A population-based case-control study
      was conducted in which the prevalence of risk factors and the medical histories
      of patients prescribed COX-2 inhibitors and traditional nonselective NSAIDs were
      compared. The study population consisted of a random sample of members of the
      Quebec drug plan (age 18 years or older) who received at least one dispensation
      of celecoxib (n = 42,422; cases), rofecoxib (n = 25,674; cases), or traditional
      nonselective NSAIDs (n = 12,418; controls) during the year 2000. All study data
      were obtained from the Quebec health care databases. Adjusting for income level,
      Chronic Disease Score, prior use of low-dose acetylsalicylic acid, acetaminophen,
      antidepressants, benzodiazepines, prescriber specialty, and time period, the
      following factors were significantly associated with the prescription of COX-2
      inhibitors: age 75 years or older (odds ratio [OR] 4.22, 95% confidence interval
      [CI] 3.95-4.51), age 55-74 years (OR 3.23, 95% CI 3.06-3.40), female sex (OR
      1.52, 95% CI 1.45-1.58), prior diagnosis of gastropathy (OR 1.21, 95% CI 1.08
      1.36) and prior dispensation of gastroprotective agents (OR 1.57, 95% CI 1.47
      1.67). Patients who received a traditional nonselective NSAID recently were more
      likely to switch to a coxib, especially first-time users (OR 2.17, 95% CI 1.93
      2.43). Associations were significantly greater for celecoxib than rofecoxib for
      age, chronic NSAID use, and last NSAID use between 1 and 3 months before the
      index date. At the time of introduction of COX-2 inhibitors into the formulary,
      prescription channeling could confound risk comparisons across products.

PMID- 15743483
TI  - Balance between survivin, a key member of the apoptosis inhibitor family, and its
      specific antibodies determines erosivity in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a highly heterogeneous disease with respect to its
      joint destructivity. The reasons underlying this heterogeneity are unknown.
      Deficient apoptosis in rheumatoid synovial tissue has been recently demonstrated.
      We have therefore decided to study the synovial expression of survivin, a key
      member of the apoptosis inhibitor family. The levels of survivin and antibodies
      against survivin were assessed by an ELISA in matched blood and synovial fluid
      samples collected from 131 RA patients. Results were related to joint erosivity
      at the time of sampling. Monocytes were transfected with survivin anti-sense
      oligonucleotides and were assessed for their ability to produce inflammatory
      cytokines. Survivin levels were significantly higher in patients with destructive
      disease as compared with in RA patients displaying a non-erosive disease. High
      survivin levels were an independent prognostic parameter for erosive RA. In
      contrast, high levels of antibodies against survivin were found in patients with
      non-erosive RA, and were negatively related to erosivity. Survivin levels in RA
      patients were influenced by treatment, being significantly lower among patients
      treated with disease-modifying anti-rheumatic drugs. Specific suppression of
      survivin mRNA resulted in downregulation of IL-6 production. We conclude that
      survivin determines the erosive course of RA, whereas survivin antibodies lead to
      a less aggressive course of the disease. These findings together with decreased
      survivin levels upon disease-modifying anti-rheumatic drug treatment, and the
      downregulation of inflammatory response using survivin anti-sense
      oligonucleotides, suggest that extracellular survivin expression mediates the
      erosive course of joint disease whereas autoimmune responses to the same
      molecule, manifested as survivin targeting antibodies, mediate protection.

PMID- 15743484
TI  - Infiltration of the synovial membrane with macrophage subsets and
      polymorphonuclear cells reflects global disease activity in spondyloarthropathy.
AB  - Considering the relation between synovial inflammation and global disease
      activity in rheumatoid arthritis (RA) and the distinct but heterogeneous
      histology of spondyloarthropathy (SpA) synovitis, the present study analyzed
      whether histopathological features of synovium reflect specific phenotypes and/or
      global disease activity in SpA. Synovial biopsies obtained from 99 SpA and 86 RA
      patients with active knee synovitis were analyzed for 15 histological and
      immunohistochemical markers. Correlations with swollen joint count, serum C
      reactive protein concentrations, and erythrocyte sedimentation rate were analyzed
      using classical and multiparameter statistics. SpA synovitis was characterized by
      higher vascularity and infiltration with CD163+ macrophages and polymorphonuclear
      leukocytes (PMNs) and by lower values for lining-layer hyperplasia, lymphoid
      aggregates, CD1a+ cells, intracellular citrullinated proteins, and MHC-HC gp39
      complexes than RA synovitis. Unsupervised clustering of the SpA samples based on
      synovial features identified two separate clusters that both contained different
      SpA subtypes but were significantly differentiated by concentration of C-reactive
      protein and erythrocyte sedimentation rate. Global disease activity in SpA
      correlated significantly with lining-layer hyperplasia as well as with
      inflammatory infiltration with macrophages, especially the CD163+ subset, and
      with PMNs. Accordingly, supervised clustering using these synovial parameters
      identified a cluster of 20 SpA patients with significantly higher disease
      activity, and this finding was confirmed in an independent SpA cohort. However,
      multiparameter models based on synovial histopathology were relatively poor
      predictors of disease activity in individual patients. In conclusion, these data
      indicate that inflammatory infiltration of the synovium with CD163+ macrophages
      and PMNs as well as lining-layer hyperplasia reflect global disease activity in
      SpA, independently of the SpA subtype. These data support a prominent role for
      innate immune cells in SpA synovitis and warrant further evaluation of synovial
      histopathology as a surrogate marker in early-phase therapeutic trials in SpA.

PMID- 15743485
TI  - TLR2 modulates inflammation in zymosan-induced arthritis in mice.
AB  - The interplay between the innate and acquired immune systems in chronic
      inflammation is not well documented. We have investigated the mechanisms of
      inflammation in murine zymosan-induced arthritis (ZIA) in the light of recent
      data on the roles of Toll-like receptor 2 (TLR2) and Dectin-1 in the activation
      of monocyte/macrophages by zymosan. The severity of inflammation, joint
      histology, lymphocyte proliferation and antibody production in response to
      zymosan were analyzed in mice deficient in TLR2 and complement C3, and the
      effects of Dectin-1 inhibition by laminarin were studied. In comparison with wild
      type animals, TLR2-deficient mice showed a significant decrease in the early (day
      1) and late phases (day 24) of joint inflammation. C3-deficient mice showed no
      differences in technetium uptake or histological scoring. TLR2-deficient mice
      also showed a significant decrease in lymph node cell proliferation in response
      to zymosan and a lower IgG antibody response to zymosan at day 25 in comparison
      with wild-type controls, indicating that TLR2 signalling has a role in the
      development of acquired immune responses to zymosan. Although laminarin, a
      soluble beta-glucan, was able to significantly inhibit zymosan uptake by
      macrophages in vitro, it had no effect on ZIA in vivo. These results show that
      ZIA is more prolonged than was originally described and involves both the innate
      and acquired immune pathways. C3 does not seem to have a major role in this model
      of joint inflammation.

PMID- 15743486
TI  - Potential involvement of oxidative stress in cartilage senescence and development
      of osteoarthritis: oxidative stress induces chondrocyte telomere instability and
      downregulation of chondrocyte function.
AB  - Oxidative stress leads to increased risk for osteoarthritis (OA) but the precise
      mechanism remains unclear. We undertook this study to clarify the impact of
      oxidative stress on the progression of OA from the viewpoint of oxygen free
      radical induced genomic instability, including telomere instability and resulting
      replicative senescence and dysfunction in human chondrocytes. Human chondrocytes
      and articular cartilage explants were isolated from knee joints of patients
      undergoing arthroplastic knee surgery for OA. Oxidative damage and antioxidative
      capacity in OA cartilage were investigated in donor-matched pairs of intact and
      degenerated regions of tissue isolated from the same cartilage explants. The
      results were histologically confirmed by immunohistochemistry for nitrotyrosine,
      which is considered to be a maker of oxidative damage. Under treatment with
      reactive oxygen species (ROS; 0.1 micromol/l H2O2) or an antioxidative agent
      (ascorbic acid: 100.0 micromol/l), cellular replicative potential, telomere
      instability and production of glycosaminoglycan (GAG) were assessed in cultured
      chondrocytes. In tissue cultures of articular cartilage explants, the presence of
      oxidative damage, chondrocyte telomere length and loss of GAG to the medium were
      analyzed in the presence or absence of ROS or ascorbic acid. Lower antioxidative
      capacity and stronger staining of nitrotyrosine were observed in the degenerating
      regions of OA cartilages as compared with the intact regions from same explants.
      Immunostaining for nitrotyrosine correlated with the severity of histological
      changes to OA cartilage, suggesting a correlation between oxidative damage and
      articular cartilage degeneration. During continuous culture of chondrocytes,
      telomere length, replicative capacity and GAG production were decreased by
      treatment with ROS. In contrast, treatment with an antioxidative agent resulted
      in a tendency to elongate telomere length and replicative lifespan in cultured
      chondrocytes. In tissue cultures of cartilage explants, nitrotyrosine staining,
      chondrocyte telomere length and GAG remaining in the cartilage tissue were lower
      in ROS-treated cartilages than in control groups, whereas the antioxidative agent
      treated group exhibited a tendency to maintain the chondrocyte telomere length
      and proteoglycan remaining in the cartilage explants, suggesting that oxidative
      stress induces chondrocyte telomere instability and catabolic changes in
      cartilage matrix structure and composition. Our findings clearly show that the
      presence of oxidative stress induces telomere genomic instability, replicative
      senescence and dysfunction of chondrocytes in OA cartilage, suggesting that
      oxidative stress, leading to chondrocyte senescence and cartilage ageing, might
      be responsible for the development of OA. New efforts to prevent the development
      and progression of OA may include strategies and interventions aimed at reducing
      oxidative damage in articular cartilage.

PMID- 15743487
TI  - Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte
      death and matrix-metalloproteinase-mediated cartilage matrix degradation despite
      enhanced joint inflammation.
AB  - During immune-complex-mediated arthritis (ICA), severe cartilage destruction is
      mediated by Fcgamma receptors (FcgammaRs) (mainly FcgammaRI), cytokines (e.g. IL
      1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2)
      cytokine abundantly found in synovial fluid of patients with rheumatoid
      arthritis, has been shown to reduce joint inflammation and bone destruction
      during experimental arthritis. However, the effect on severe cartilage
      destruction has not been studied in detail. We have now investigated the role of
      IL-13 in chondrocyte death and MMP-mediated cartilage damage during ICA. IL-13
      was locally overexpressed in knee joints after injection of an adenovirus
      encoding IL-13 (AxCAhIL-13), 1 day before the onset of arthritis; injection of
      AxCANI (an empty adenoviral construct) was used as a control. IL-13 significantly
      increased the amount of inflammatory cells in the synovial lining and the joint
      cavity, by 30% to 60% at day 3 after the onset of ICA. Despite the enhanced
      inflammatory response, chondrocyte death was diminished by two-thirds at days 3
      and 7. The mRNA level of FcgammaRI, a receptor shown to be crucial in the
      induction of chondrocyte death, was significantly down-regulated in synovium.
      Furthermore, MMP-mediated cartilage damage, measured as neoepitope (VDIPEN)
      expression using immunolocalization, was halved. In contrast, mRNA levels of MMP
      3, -9, -12, and -13 were significantly higher and IL-1 protein, which induces
      production of latent MMPs, was increased fivefold by IL-13. This study
      demonstrates that IL-13 overexpression during ICA diminished both chondrocyte
      death and MMP-mediated VDIPEN expression, even though joint inflammation was
      enhanced.

PMID- 15743488
TI  - Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis:
      an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma.
AB  - Mice with a deficiency in IFN-gamma or IFN-gamma receptor (IFN-gammaR) are more
      susceptible to collagen-induced arthritis (CIA), an experimental autoimmune
      disease that relies on the use of complete Freund's adjuvant (CFA). Here we
      report that the heightened susceptibility of IFN-gammaR knock-out (KO) mice is
      associated with a functional impairment of CD4+CD25+ Treg cells. Treatment of
      wild-type mice with depleting anti-CD25 antibody after CFA-assisted immunisation
      with collagen type II (CII) significantly accelerated the onset of arthritis and
      increased the severity of CIA. This is an indication of a role of Treg cells in
      the effector phase of CIA. IFN-gammaR deficiency did not affect the number of
      CD4+CD25+ T cells in the central and peripheral lymphoid tissues. In addition,
      CD4+CD25+ T cells isolated from naive IFN-gammaR KO mice had a normal potential
      to suppress T cell proliferation in vitro. However, after immunisation with CII
      in CFA, the suppressive activity of CD4+CD25+ T cells became significantly more
      impaired in IFN-gammaR-deficient mice. Moreover, expression of the mRNA for
      Foxp3, a highly specific marker for Treg cells, was lower. We further
      demonstrated that the effect of endogenous IFN-gamma, which accounts for more
      suppressive activity in wild-type mice, concerns both Treg cells and accessory
      cells. Our results demonstrate that the decrease in Treg cell activity in CIA is
      counter-regulated by endogenous IFN-gamma.

PMID- 15743489
TI  - Building the synovium: cadherin-11 mediates fibroblast-like synoviocyte cell-to
      cell adhesion.
AB  - Specific adhesion among like cells is a key determinant of the architecture of
      tissues. Homophilic (like binds like) adhesive interactions between cells are
      mediated by cadherins. These integral membrane glycoproteins have a crucial role
      in tissue morphogenesis during development and the maintenance of tissue
      integrity in adults. There is also an increasing recognition of a regulatory role
      for cadherins in a variety of cell functions, including cell migration. The
      recent identification of cadherin-11 expression in fibroblast-like synoviocytes
      (FLSs) has shed light on the mechanisms of synovial tissue organization and
      differentiation. Moreover, cadherin-11 expression in FLSs might also provide
      insight into pathways that determine the mesenchymal tissue response of the
      synovium to inflammation.

PMID- 15743490
TI  - Do the pleiotropic effects of statins in the vasculature predict a role in
      inflammatory diseases?
AB  - Pleiotropic effects are now described for the 3-hydroxy-3-methylglutaryl-coenzyme
      A reductase inhibitors (or statins) that might have utility in the context of
      chronic inflammatory autoimmune disease. Here we discuss the pharmacology and
      established uses of statins and in this context describe potential anti
      inflammatory and immune-modulatory effects. An extensive in vitro data set
      defines roles for statins in modifying endothelial function, particularly with
      respect to adhesion molecule expression and apoptosis. Broader effects on
      leukocyte function have now emerged including altered adhesion molecule
      expression, cytokine and chemokine release and modulation of development of
      adaptive immune responses via altered MHC class II upregulation. In vivo data in
      several inflammatory models, including collagen-induced inflammatory arthritis
      and experimental autoimmune encephalomyelitis, suggest that such effects might
      have immune-modulatory potential. Finally, a recent clinical trial has
      demonstrated immunomodulatory effects for statins in patients with rheumatoid
      arthritis. Together with their known vasculoprotective effects, this growing body
      of evidence provides compelling support for longer-term trials of statin therapy
      in human disease such as rheumatoid arthritis.

PMID- 15743491
TI  - Transforming growth factor-beta-induced regulatory T cells referee inflammatory
      and autoimmune diseases.
AB  - Naturally occurring CD4+CD25+ regulatory T cells mediate immune suppression to
      limit immunopathogenesis associated with chronic inflammation, persistent
      infections and autoimmune diseases. Their mode of suppression is contact
      dependent, antigen-nonspecific and involves a nonredundant contribution from the
      cytokine transforming growth factor (TGF)-beta. Not only can TGF-beta mediate
      cell-cell suppression between the regulatory T cells and CD4+CD25- or CD8+ T
      cells, but new evidence also reveals its role in the conversion of CD4+CD25- T
      cells, together with TCR antigen stimulation, into the regulatory phenotype.
      Elemental to this conversion process is induction of expression of the forkhead
      transcription factor, Foxp3. This context-dependent coercion of naive CD4+ T
      cells into a powerful subset of regulatory cells provides a window into potential
      manipulation of these cells to orchestrate therapeutic intervention in diseases
      characterized by inadequate suppression, as well as a promising means of
      controlling pathologic situations in which excessive suppression dominates.

PMID- 15743492
TI  - Anti-SSA/Ro antibodies and the heart: more than complete congenital heart block?
      A review of electrocardiographic and myocardial abnormalities and of treatment
      options.
AB  - Apart from complete and incomplete congenital heart block (CHB), new cardiac
      manifestations related to anti-SSA/Ro antibodies have been reported in children
      born to mothers bearing these antibodies. These manifestations include transient
      fetal first-degree heart block, prolongation of corrected QT (QTc) interval,
      sinus bradycardia, late-onset cardiomyopathy, endocardial fibroelastosis and
      cardiac malformations. Anti-SSA/Ro antibodies are not considered pathogenic to
      the adult heart, but a prolongation of the QTc interval has recently been
      reported in adult patients and is still a matter of debate. Treatment of CHB is
      not well established and needs to be assessed carefully. The risks and benefits
      of prenatal fluorinated steroids are discussed.

PMID- 15743495
TI  - Natural killer T cells and rheumatoid arthritis: friend or foe?

PMID- 15743494
TI  - Is closer linkage between systemic lupus erythematosus and anti-double-stranded
      DNA antibodies a desirable and attainable goal?
AB  - The anti-double-stranded DNA (anti-dsDNA) antibody test incorporated in the 1982
      revised American College of Rheumatology criteria for the classification of
      systemic lupus erythematosus needs updating to reflect current insights and
      technical achievements, including allowance for the presence of nonpathogenic
      anti-dsDNA antibodies. As we need to develop at least some measure of
      pathogenicity of anti-dsDNA antibodies, we propose that initial anti-dsDNA
      antibody screening is done by sensitive ELISA and supplemented by more stringent
      assays. Simultaneously the relevance of anti-dsDNA antibody presence needs to be
      restricted to clinical manifestations, thought to be caused by anti-dsDNA
      antibody and within an appropriate time frame.

PMID- 15743496
TI  - Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic
      breast cancer.
AB  - INTRODUCTION: Truncation mutations in the BRCA1 gene cause a substantial increase
      in risk of breast cancer. However, these mutations are rare in the general
      population and account for little of the overall incidence of sporadic breast
      cancer. METHOD: We used whole-gene resequencing data to select haplotype tagging
      single nucleotide polymorphisms, and examined the association between common
      haplotypes of BRCA1 and breast cancer in a nested case-control study in the
      Nurses' Health Study (1323 cases and 1910 controls). RESULTS: One haplotype was
      associated with a slight increase in risk (odds ratio 1.18, 95% confidence
      interval 1.02-1.37). A significant interaction (P = 0.05) was seen between this
      haplotype, positive family history of breast cancer, and breast cancer risk.
      Although not statistically significant, similar interactions were observed with
      age at diagnosis and with menopausal status at diagnosis; risk tended to be
      higher among younger, pre-menopausal women. CONCLUSIONS: We have described a
      haplotype in the BRCA1 gene that was associated with an approximately 20%
      increase in risk of sporadic breast cancer in the general population. However,
      the functional variant(s) responsible for the association are unclear.

PMID- 15743493
TI  - Amplification of autoimmune disease by infection.
AB  - Reports of infection with certain chronic persistent microbes (herpesviruses or
      Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that
      these microbes are reactivated in the setting of immunodeficiency and often
      target the site of autoimmune inflammation. New experimental animal models
      demonstrate the principle. A herpesvirus or Chlamydia species can be used to
      infect mice with induced transient autoimmune diseases. This results in increased
      disease severity and even relapse. The evidence suggests that the organisms are
      specifically imported to the inflammatory sites and cause further tissue
      destruction, especially when the host is immunosuppressed. We review the evidence
      for the amplification of autoimmune inflammatory disease by microbial infection,
      which may be a general mechanism applicable to many human diseases. We suggest
      that patients with autoimmune disorders receiving immunosuppressing drugs should
      benefit from preventive antiviral therapy.

PMID- 15743497
TI  - The androgen receptor CAG repeat polymorphism and modification of breast cancer
      risk in BRCA1 and BRCA2 mutation carriers.
AB  - INTRODUCTION: The androgen receptor (AR) gene exon 1 CAG repeat polymorphism
      encodes a string of 9-32 glutamines. Women with germline BRCA1 mutations who
      carry at least one AR allele with 28 or more repeats have been reported to have
      an earlier age at onset of breast cancer. METHODS: A total of 604 living female
      Australian and British BRCA1 and/or BRCA2 mutation carriers from 376 families
      were genotyped for the AR CAG repeat polymorphism. The association between AR
      genotype and disease risk was assessed using Cox regression. AR genotype was
      analyzed as a dichotomous covariate using cut-points previously reported to be
      associated with increased risk among BRCA1 mutation carriers, and as a continuous
      variable considering smaller allele, larger allele and average allele size.
      RESULTS: There was no evidence that the AR CAG repeat polymorphism modified
      disease risk in the 376 BRCA1 or 219 BRCA2 mutation carriers screened
      successfully. The rate ratio associated with possession of at least one allele
      with 28 or more CAG repeats was 0.74 (95% confidence interval 0.42-1.29; P = 0.3)
      for BRCA1 carriers, and 1.12 (95% confidence interval 0.55-2.25; P = 0.8) for
      BRCA2 carriers. CONCLUSION: The AR exon 1 CAG repeat polymorphism does not appear
      to have an effect on breast cancer risk in BRCA1 or BRCA2 mutation carriers.

PMID- 15743498
TI  - Breast implants following mastectomy in women with early-stage breast cancer:
      prevalence and impact on survival.
AB  - BACKGROUND: Few studies have examined the effect of breast implants after
      mastectomy on long-term survival in breast cancer patients, despite growing
      public health concern over potential long-term adverse health effects. METHODS:
      We analyzed data from the Surveillance, Epidemiology and End Results Breast
      Implant Surveillance Study conducted in San Francisco-Oakland, in Seattle-Puget
      Sound, and in Iowa. This population-based, retrospective cohort included women
      younger than 65 years when diagnosed with early or unstaged first primary breast
      cancer between 1983 and 1989, treated with mastectomy. The women were followed
      for a median of 12.4 years (n = 4968). Breast implant usage was validated by
      medical record review. Cox proportional hazards models were used to estimate
      hazard rate ratios for survival time until death due to breast cancer or other
      causes for women with and without breast implants, adjusted for relevant patient
      and tumor characteristics. RESULTS: Twenty percent of cases received
      postmastectomy breast implants, with silicone gel-filled implants comprising the
      most common type. Patients with implants were younger and more likely to have in
      situ disease than patients not receiving implants. Risks of breast cancer
      mortality (hazard ratio, 0.54; 95% confidence interval, 0.43-0.67) and nonbreast
      cancer mortality (hazard ratio, 0.59; 95% confidence interval, 0.41-0.85) were
      lower in patients with implants than in those patients without implants,
      following adjustment for age and year of diagnosis, race/ethnicity, stage, tumor
      grade, histology, and radiation therapy. Implant type did not appear to influence
      long-term survival. CONCLUSIONS: In a large, population-representative sample,
      breast implants following mastectomy do not appear to confer any survival
      disadvantage following early-stage breast cancer in women younger than 65 years
      old.

PMID- 15743499
TI  - Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in
      vitro and in vivo.
AB  - INTRODUCTION: Breast cancer is the leading cause of cancer death in women
      worldwide. Elevated expression of c-Myc is a frequent genetic abnormality seen in
      this malignancy. For a better understanding of its role in maintaining the
      malignant phenotype, we used RNA interference (RNAi) directed against c-Myc in
      our study. RNAi provides a new, reliable method to investigate gene function and
      has the potential for gene therapy. The aim of the study was to examine the anti
      tumor effects elicited by a decrease in the protein level of c-Myc by RNAi and
      its possible mechanism of effects in MCF-7 cells. METHOD: A plasmid-based
      polymerase III promoter system was used to deliver and express short interfering
      RNA (siRNA) targeting c-myc to reduce its expression in MCF-7 cells. Western blot
      analysis was used to measure the protein level of c-Myc. We assessed the effects
      of c-Myc silencing on tumor growth by a growth curve, by soft agar assay and by
      nude mice experiments in vivo. Standard fluorescence-activated cell sorter
      analysis and TdT-mediated dUTP nick end labelling assay were used to determine
      apoptosis of the cells. RESULTS: Our data showed that plasmids expressing siRNA
      against c-myc markedly and durably reduced its expression in MCF-7 cells by up to
      80%, decreased the growth rate of MCF-7 cells, inhibited colony formation in soft
      agar and significantly reduced tumor growth in nude mice. We also found that
      depletion of c-Myc in this manner promoted apoptosis of MCF-7 cells upon serum
      withdrawal. CONCLUSION: c-Myc has a pivotal function in the development of breast
      cancer. Our data show that decreasing the c-Myc protein level in MCF-7 cells by
      RNAi could significantly inhibit tumor growth both in vitro and in vivo, and
      imply the therapeutic potential of RNAi on the treatment of breast cancer by
      targeting overexpression oncogenes such as c-myc, and c-myc might be a potential
      therapeutic target for human breast cancer.

PMID- 15743500
TI  - High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer
      is related to overexpression of HER-2/neu and activated Akt kinase but does not
      predict outcome.
AB  - INTRODUCTION: Focal adhesion kinase (FAK) regulates multiple cellular processes
      including growth, differentiation, adhesion, motility and apoptosis. In breast
      carcinoma, FAK overexpression has been linked to cancer progression but the
      prognostic relevance remains unknown. In particular, with regard to lymph node
      negative breast cancer it is important to identify high-risk patients who would
      benefit from further adjuvant therapy. METHODS: We analyzed 162 node-negative
      breast cancer cases to determine the prognostic relevance of FAK expression, and
      we investigated the relationship of FAK with major associated signaling pathways
      (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and
      western blot analysis. RESULTS: Elevated FAK expression did not predict patient
      outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383)
      and estrogen receptor status (P = 0.0033). Significant positive correlations were
      observed between elevated FAK expression and HER2 overexpression (P = 0.001), as
      well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with
      phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant
      correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01).
      CONCLUSIONS: Immunohistochemical detection of FAK expression is of no prognostic
      significance in node-negative breast cancer but provides evidence that HER2 is
      involved in tumor malignancy and metastatic ability of breast cancer through a
      novel signaling pathway participating FAK and Src.

PMID- 15743501
TI  - Common ERBB2 polymorphisms and risk of breast cancer in a white British
      population: a case-control study.
AB  - INTRODUCTION: About two-thirds of the excess familial risk associated with breast
      cancer is still unaccounted for and may be explained by multiple weakly
      predisposing alleles. A gene thought to be involved in low-level predisposition
      to the disease is ERBB2 (HER2). This gene is involved in cell division,
      differentiation, and apoptosis and is frequently amplified in breast tumours. Its
      amplification correlates with poor prognosis. Moreover, the coding polymorphism
      I655V has previously been associated with an increased risk of breast cancer.
      METHODS: We aimed to determine if common polymorphisms (frequency >or= 5%) in
      ERBB2 were associated with breast cancer risk in a white British population. Five
      single-nucleotide polymorphisms (SNPs) were selected for study: SNP 1 near the
      promoter, SNP 2 in intron 1, SNP 3 in intron 4, SNP 4 in exon 17 (I655V), and SNP
      5 in exon 27 (A1170P). We tested their association with breast cancer in a large
      case-control study (n = 2192 cases and 2257 controls). RESULTS: There were no
      differences in genotype frequencies between cases and controls for any of the
      SNPs examined. To investigate the possibility that a common polymorphism not
      included in our study might be involved in breast cancer predisposition, we also
      constructed multilocus haplotypes. Our set of SNPs generated all existing (n = 6)
      common haplotypes and no differences were seen in haplotype frequencies between
      cases and controls (P = 0.44). CONCLUSIONS: In our population, common ERBB2
      polymorphisms are not involved in predisposition to breast cancer.

PMID- 15743503
TI  - SULT1A1 genotype, active and passive smoking, and breast cancer risk by age 50
      years in a German case-control study.
AB  - INTRODUCTION: Sulfotransferase 1A1 (encoded by SULT1A1) is involved in the
      metabolism of procarcinogens such as heterocyclic amines and polycyclic aromatic
      hydrocarbons, both of which are present in tobacco smoke. We recently reported a
      differential effect of N-acetyltransferase (NAT) 2 genotype on the association
      between active and passive smoking and breast cancer. Additional investigation of
      a common SULT1A1 genetic polymorphism associated with reduced enzyme activity and
      stability might therefore provide deeper insight into the modification of breast
      cancer susceptibility. METHODS: We conducted a population-based case-control
      study in Germany. A total of 419 patients who had developed breast cancer by age
      50 years and 884 age-matched control individuals, for whom risk factor
      information and detailed smoking history were available, were included in the
      analysis. Genotyping was performed using a fluorescence-based melting curve
      analysis method. Multivariate logistic regression analysis was used to estimate
      breast cancer risk associated with the SULT1A1 Arg213His polymorphism alone and
      in combination with NAT2 genotype in relation to smoking. RESULTS: The overall
      risk for breast cancer in women who were carriers of at least one SULT1A1*2
      allele was not significantly different from that for women with the SULT1A1*1/*1
      genotype (adjusted odds ratio 0.83, 95% confidence interval 0.66-1.06). Risk for
      breast cancer with respect to several smoking variables did not differ
      substantially between carriers of the *2 allele and noncarriers. However, among
      NAT2 fast acetylators, the odds ratio associated with passive smoking only (3.23,
      95% confidence interval 1.05-9.92) was elevated in homozygous carriers of the
      SULT1A1*1 allele but not in carriers of the SULT1A1*2 allele (odds ratio 1.28,
      95% confidence interval 0.50-3.31). CONCLUSION: We found no evidence that the
      SULT1A1 genotype in itself modifies breast cancer risk associated with smoking in
      women up to age 50 years. In combination with NAT2 fast acetylator status,
      however, the SULT1A1*1/*1 genotype might increase breast cancer risk in women
      exposed to tobacco smoke.

PMID- 15743502
TI  - Relative microvessel area of the primary tumour, and not lymph node status,
      predicts the presence of bone marrow micrometastases detected by reverse
      transcriptase polymerase chain reaction in patients with clinically non
      metastatic breast cancer.
AB  - About 50% of patients with breast cancer have no involvement of axillary lymph
      nodes at diagnosis and can be considered cured after primary locoregional
      treatment. However, about 20-30% will experience distant relapse. The group of
      patients at risk is not well characterised: recurrence is probably due to the
      establishment of micrometastases before treatment. Given the early steps of
      metastasis in which tumour cells interact with endothelial cells of blood
      vessels, and, given the independent prognostic value in breast cancer of both the
      quantification of tumour vascularisation and the detection of micrometastases in
      the bone marrow, the aim of this study was to determine the relationship between
      vascularisation, measured by Chalkley morphometry, and the bone marrow content of
      cytokeratin-19 (CK-19) mRNA, quantified by real-time reverse transcriptase
      polymerase chain reaction, in a series of 68 patients with localised untreated
      breast cancer. The blood concentration of factors involved in angiogenesis
      (interleukin-6 and vascular endothelial growth factor) and of factors involved in
      coagulation (D-dimer, fibrinogen, platelets) was also measured. When bone marrow
      CK-19 relative gene expression (RGE) was categorised according to the cut-off
      value of 0.77 (95th centile of control patients), 53% of the patients had an
      elevated CK-19 RGE. Patients with bone marrow micrometastases, on the basis of an
      elevated CK-19 RGE, had a mean Chalkley count of 7.5 +/- 1.7 (median 7, standard
      error [SE] 0.30) compared with a mean Chalkley count of 6.5 +/- 1.7 in other
      patients (median 6, SE 0.3) (Mann-Whitney U-test; P = 0.04). Multiple regression
      analysis revealed that Chalkley count, not lymph node status, independently
      predicted CK-19 RGE status (P = 0.04; odds ratio 1.38; 95% confidence interval
      1.009-1.882). Blood parameters reflecting angiogenesis and coagulation were
      positively correlated with Chalkley count and/or CK-19 RGE. Our data are in
      support of an association between elevated relative microvessel area of the
      primary tumour and the presence of bone marrow micrometastases in breast cancer
      patients with operable disease, and corroborate the paracrine and endocrine role
      of interleukin-6 and the involvement of coagulation in breast cancer growth and
      metastasis.

PMID- 15743504
TI  - Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal
      carcinomas of the breast and its clinicopathologic relationships.
AB  - INTRODUCTION: The anaphase-promoting complex (APC) is a multiprotein complex with
      E3 ubiquitin ligase activity, which is required for the ubiquitination of securin
      and cyclin-B. Moreover, the mitotic spindle checkpoint is activated if APC
      activation is prevented. In addition, several APC-targeting molecules such as
      securin, polo-like kinase, aurora kinase, and SnoN have been reported to be
      oncogenes. Therefore, dysregulation of APC may be associated with tumorigenesis.
      However, the clinical significance and the involvement of APC in tumorigenesis
      have not been investigated. METHODS: The expression of APC7 was
      immunohistochemically investigated in 108 invasive ductal carcinomas of the
      breast and its relationship with clinicopathologic parameters was examined. The
      expression of APC7 was defined as positive when the summed scores of staining
      intensities (0 to 3+) and stained proportions (0 to 3+) exceeded 3+. RESULTS:
      Positive APC7 expression was less frequent than its negative expression when
      histologic (P = 0.009) or nuclear grade (P = 0.009), or mitotic number (P =
      0.0016) was elevated. The frequency of APC7 negative expression was higher in
      high Ki-67 or aneuploid groups than in low Ki-67 or diploid groups. CONCLUSION:
      These data show that loss of APC7 expression is more common in breast carcinoma
      cases with poor prognostic parameters or malignant characteristics. They
      therefore suggest that dysregulation of APC activity, possibly through
      downregulation of APC7, may be associated with tumorigenesis in breast cancer.

PMID- 15743505
TI  - Claudin 7 expression and localization in the normal murine mammary gland and
      murine mammary tumors.
AB  - INTRODUCTION: Claudins, membrane-associated tetraspanin proteins, are normally
      associated with the tight junctions of epithelial cells where they confer a
      variety of permeability properties to the transepithelial barrier. One member of
      this family, claudin 7, has been shown to be expressed in the human mammary
      epithelium and some breast tumors. To set the stage for functional experiments on
      this molecule, we examined the developmental expression and localization of
      claudin 7 in the murine mammary epithelium and in a selection of murine mammary
      tumors. METHOD: We used real-time polymerase chain reaction, in situ mRNA
      localization, and immunohistochemistry (IHC) to examine the expression and
      localization of claudin 7. Frozen sections were examined by digital confocal
      microscopy for colocalization with the tight-junction protein ZO1. RESULTS:
      Claudin 7 was expressed constitutively in the mammary epithelium at all
      developmental stages, and the ratio of its mRNA to that of keratin 19 was nearly
      constant through development. By IHC, claudin 7 was located in the basolateral
      part of the cell where it seemed to be localized to discrete vesicles. Scant
      colocalization with the tight-junction scaffolding protein ZO1 was observed.
      Similar results were obtained from IHC of the airway epithelium and some renal
      tubules; however, claudin 7 did partly colocalize with ZO1 in EPH4 cells, a
      normal murine mammary cell line, and in the epididymis. The molecule was
      localized in the cytoplasm of MMTV-neu and the transplantable murine tumor cell
      lines TM4, TM10, and TM40A, in which its ratio to cytokeratin was higher than in
      the normal mammary epithelium. CONCLUSION: Claudin 7 is expressed constitutively
      in the mammary epithelium at approximately equal levels throughout development as
      well as in the murine tumors examined. Although it is capable of localizing to
      tight junctions, in the epithelia of mammary gland, airway, and kidney it is
      mostly or entirely confined to punctate cytoplasmic structures, often near the
      basolateral surfaces of the cells and possibly associated with basolateral
      membranes. These observations suggest that claudin 7 might be involved in vesicle
      trafficking to the basolateral membrane, possibly stabilizing cytoplasmic
      vesicles or participating in cell-matrix interactions.

PMID- 15743506
TI  - Long-term prognostic significance of HER-2/neu in untreated node-negative breast
      cancer depends on the method of testing.
AB  - INTRODUCTION: The prognostic significance of HER-2/neu in breast cancer is a
      matter of controversy. We have performed a study in 101 node-negative breast
      cancer patients with long-term follow-up not treated in the adjuvant setting, and
      analysed the prognostic significance of immunohistochemistry (IHC) and
      fluorescence in situ hybridisation (FISH), both separately and in combination, in
      comparison with traditional prognostic factors. METHODS: Overexpression was
      classified semiquantitatively according to a score (0 to 3+) (HER-2_SCO). FISH
      was used to analyse HER2/neu amplification (HER-2_AMP). Patients classified 2+ by
      IHC were examined with FISH for amplification (HER-2_ALG). Patients with 3+
      overexpression as well as amplification of HER-2/neu were positive for the
      combined variable HER2_COM. These variables were compared with tumour size,
      histological grade and hormone receptor status. RESULTS: HER-2_SCO was 3+ in 20%
      of all tumours. HER-2_ALG was positive in 22% and amplification (HER-2_AMP) was
      found in 17% of all tumours. Eleven percent of the tumours showed simultaneous 3+
      overexpression and amplification. Only histological grade (relative risk [RR]
      3.22, 95% confidence interval [CI] 1.73-5.99, P = 0.0002) and HER-2_AMP (RR 2.47,
      95% CI 1.12-5.48, P = 0.026) were significant for disease-free survival in
      multivariate analysis. For overall survival, both histological grade (RR 3.89,
      95% CI 1.77-8.55, P = 0.0007) and HER-2_AMP (RR 3.08, 95% CI 1.24-7.66, P =
      0.016) retained their independent significance. CONCLUSION: The prognostic
      significance of HER-2/neu in node-negative breast cancer depends on the method of
      testing: only the amplification of HER-2/neu is an independent prognostic factor
      for the long-term prognosis of untreated node-negative breast cancer.

PMID- 15743509
TI  - The challenge of measuring circulating estradiol at low concentrations.
AB  - Demand for measuring estradiol at low concentrations is increasing, and the
      widely used 'direct' radioimmunoassays that do not require a preliminary organic
      purification step may be inadequate in patient care because of their limited
      accuracy. In observational epidemiology, however, the main concern is to obtain a
      correct ranking of individuals' hormone concentration relative to the true level
      (as determined through a 'gold standard'). Despite differences in the absolute
      scale of measured and true concentrations, correct ranking will permit
      calculation of unbiased estimates of hormone-disease associations. In prospective
      studies, the major concerns are the limited volume of often irreplaceable
      specimens and the need to perform a large number of assays within a reasonable
      period of time. Organic purification is often not feasible because of sample
      volume requirements and logistic difficulties, and so the development of
      accurate, rapid and inexpensive methods to measure sex steroids at low
      concentrations would represent a valuable new research tool for both clinicians
      and epidemiologists.

PMID- 15743507
TI  - Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of
      ERBB2: a study of 175 cases using fluorescence in situ hybridization and
      immunohistochemistry.
AB  - INTRODUCTION: One of the most common genetic aberrations associated with breast
      cancer is the amplification and overexpression of the ERBB2 proto-oncogene
      located at chromosome 17, bands q12-21. The amplification/overexpression occurs
      in 25 to 30% of all breast cancers. In breast cancer, aneusomy of chromosome 17,
      either monosomy or polysomy, is frequently observed by conventional cytogenetics
      and fluorescence in situ hybridization (FISH). The aim of this study was to
      discover whether or not numerical aberrations on chromosome 17 have a correlation
      to the amplification or overexpression of the ERBB2 gene and to analyze their
      clinical implications in subgroups showing 2+ or 3+ positive scores by
      immunohistochemistry (IHC). METHODS: We used FISH on a series of 175 formalin
      fixed paraffin-embedded breast carcinomas to detect ERBB2 amplification, using a
      dual-probe system for the simultaneous enumeration of the ERBB2 gene and the
      centromeric region of chromosome 17, as well as using IHC to detect
      overexpression. We analyzed clinical and pathological variables in a subgroup of
      patients with 2+ and 3+ IHC scores (147 patients), to describe any differences in
      clinicopathological characteristics between polysomic and non-polysomic cases
      with the use of the chi2 test. RESULTS: We found 13% of cases presenting
      polysomy, and three cases presented monosomy 17 (2%). According to the status of
      the ERBB2 gene, instances of polysomy 17 were more frequently observed in non
      amplified cases than in FISH-amplified cases, suggesting that the mechanism for
      ERBB2 amplification is independent of polysomy 17. Polysomy 17 was detected in
      patients with 2+ and 3+ IHC scores. We found that nodal involvement was more
      frequent in polysomic than in non-polysomic cases (P = 0.046). CONCLUSIONS: The
      determination of the copy number of chromosome 17 should be incorporated into the
      assesment of ERBB2 status. It might also be helpful to differentiate a subgroup
      of breast cancer patients with polysomy of chromosome 17 and overexpression of
      ERBB2 protein that probably have genetic and clinical differences.

PMID- 15743508
TI  - Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast
      lesions: a research study.
AB  - INTRODUCTION: We compared levels of protein and mRNA expression of three members
      of the claudin (CLDN) family in malignant breast tumours and benign lesions.
      METHODS: Altogether, 56 sections from 52 surgically resected breast specimens
      were analyzed for CLDN1, CLDN3 and CLDN4 expression by immunohistochemistry. mRNA
      was also analyzed using real-time PCR in 17 of the 52 cases. RESULTS: CLDNs were
      rarely observed exclusively at tight junction structures. CLDN1 was present in
      the membrane of normal duct cells and in some of the cell membranes from ductal
      carcinoma in situ, and was frequently observed in eight out of nine areas of
      apocrine metaplasia, whereas invasive tumours were negative for CLDN1 or it was
      present in a scattered distribution among such tumour cells (in 36/39 malignant
      tumours). CLDN3 was present in 49 of the 56 sections and CLDN4 was present in all
      56 tissue sections. However, CLDN4 was highly positive in normal epithelial cells
      and was decreased or absent in 17 out of 21 ductal carcinoma grade 1, in special
      types of breast carcinoma (mucinous, papillary, tubular) and in areas of apocrine
      metaplasia. CLDN1 mRNA was downregulated by 12-fold in the sample (tumour) group
      as compared with the control group using GAPDH as the reference gene. CLDN3 and
      CLDN4 mRNA exhibited no difference in expression between invasive tumours and
      surrounding tissue. CONCLUSIONS: The significant loss of CLDN1 protein in breast
      cancer cells suggests that CLDN1 may play a role in invasion and metastasis. The
      loss of CLDN4 expression in areas of apocrine metaplasia and in the majority of
      grade 1 invasive carcinomas also suggests a particular role for this protein in
      mammary glandular cell differentiation and carcinogenesis.

PMID- 15743510
TI  - Clinical trial update: National Cancer Institute of Canada.
AB  - The Breast Cancer Site Group (BCSG) of the National Cancer Institute of Canada
      (NCIC) Clinical Trials Group (CTG) has conducted a wide variety of clinical
      trials focussing on large phase III trials of adjuvant chemotherapy, adjuvant
      hormonal therapy, and optimal delivery of adjuvant radiation therapy. The Group
      has also fostered, together with the NCIC CTG Investigational New Drug (IND)
      Program, a series of phase II and phase I/II studies which will be carried
      through if possible, into the phase III setting.

PMID- 15743511
TI  - Update on inflammatory breast cancer.
AB  - Inflammatory breast cancer (IBC) is both the least frequent and the most severe
      form of epithelial breast cancer. The diagnosis is based on clinical inflammatory
      signs and is reinforced by pathological findings. Significant progress has been
      made in the management of IBC in the past 20 years. Yet survival among IBC
      patients is still only one-half that among patients with non-IBC. Identification
      of the molecular determinants of IBC would probably lead to more specific
      treatments and to improved survival. In the present article we review recent
      advances in the molecular pathogenesis of IBC. A more comprehensive view will
      probably be obtained by pan-genomic analysis of human IBC samples, and by
      functional in vitro and in vivo assays. These approaches may offer better patient
      outcome in the near future.

PMID- 15743512
TI  - Do breast implants after a mastectomy affect subsequent prognosis and survival?
AB  - In a large study, published in this issue of Breast Cancer Research, Le and
      colleagues report that women receiving implants after mastectomies for early
      stage breast cancer experience lower breast cancer mortality than women not
      receiving implants. Assessment of survival patterns among women receiving
      reconstructive implants is complex given unique patient characteristics, disease
      attributes, and treatment patterns. The interpretation of reduced mortality from
      breast cancer must be assessed in light of significantly reduced risks of death
      from most other causes. In contrast, patients receiving post-mastectomy implants
      had elevated rates of suicide, consistent with findings among women with cosmetic
      implants. Additional well-designed investigations are needed to clarify survival
      patterns among women receiving reconstructive implants.

PMID- 15743513
TI  - Dose-dense adjuvant chemotherapy for primary breast cancer.
AB  - Adjuvant chemotherapy has been proven to reduce significantly the risk for
      relapse and death in women with operable breast cancer. Nevertheless, the
      prognosis for patients presenting with extensive axillary lymph node involvement
      remains suboptimal. In an attempt to improve on the efficacy of existing
      chemotherapy, a phase III intergroup trial led by the Cancer and Leukemia Group B
      (CALGB 97-41) was designed, which tested a mathematical model of tumor growth
      based on the Norton-Simon hypothesis. This hypothesis, developed about 3 decades
      ago, and the kinetic model derived from it, created the basis of the concepts of
      dose density and sequential therapy, both of which were tested in CALGB 97-41.
      This large prospective randomized trial demonstrated that shortening the time
      interval between each chemotherapy cycle while maintaining the same dose size
      resulted in significant improvements in disease-free and overall survival in
      patients with node-positive breast carcinoma. This finding is highly relevant and
      has immediate implications for clinical practice.

PMID- 15743515
TI  - Show me the genes - I will tell you who/how to treat!

PMID- 15743514
TI  - Endocrinology and hormone therapy in breast cancer: endocrine therapy in
      premenopausal women.
AB  - Endocrine therapy remains important in premenopausal women with hormone receptor
      positive breast cancer. Ovarian ablation, used alone, is effective in delaying
      recurrence and increasing survival in such women. When added to chemotherapy, it
      is less clear that it is effective perhaps because of the endocrine ablative
      effect of chemotherapy. Trials comparing ovarian ablation with or without
      tamoxifen to CMF-type chemotherapy suggest that the endocrine therapy is
      equivalent to or better than this chemotherapy in women whose tumors have
      estrogen and/or progesterone receptor. Tamoxifen is also effective in preventing
      recurrence and prolonging survival in the adjuvant setting in premenopausal
      women. While most of the available data deals with tamoxifen given alone, it
      appears to have a similar beneficial effect when added to chemotherapy in the
      premenopausal adjuvant setting. Adjuvant aromatase inhibitors should not be used
      in premenopausal women.

PMID- 15743516
TI  - Prevalence, types and demographic features of child labour among school children
      in Nigeria.
AB  - BACKGROUND: To determine the prevalence, types and demographic features of child
      labour among school children in Nigeria. METHODS: A cross-sectional interview
      study of 1675 randomly selected public primary and secondary school pupils aged 5
      to less than 18 years was conducted in the Sagamu Local Government Area of Ogun
      State, Nigeria from October 1998 to September 1999. RESULTS: The overall
      prevalence of child labour was 64.5%: 68.6% among primary and 50.3% among
      secondary school pupils. Major economic activities included street trading
      (43.6%), selling in kiosks and shops (25.4%) and farming (23.6%). No child was
      involved in bonded labour or prostitution. Girls were more often involved in
      labour activities than boys (66.8% versus 62.1%, p = 0.048): this difference was
      most obvious with street trading (p = 0.0004). Most of the children (82.2%)
      involved in labour activities did so on the instruction of one or both parents in
      order to contribute to family income. Children of parents with low socio-economic
      status or of poorly educated parents were significantly involved in labour
      activities (p = 0.01 and p = 0.001 respectively). Child labour was also
      significantly associated with increasing number of children in the family size (p
      = 0.002). A higher prevalence rate of child labour was observed among children
      living with parents and relations than among those living with unrelated
      guardians. CONCLUSION: It is concluded that smaller family size, parental
      education and family economic enhancement would reduce the pressure on parents to
      engage their children in labour activities.

PMID- 15743518
TI  - Using equilibrium frequencies in models of sequence evolution.
AB  - BACKGROUND: The f factor is a new parameter for accommodating the influence of
      both the starting and ending states in the rate matrices of "generalized weighted
      frequencies" (+gwF) models for sequence evolution. In this study, we derive an
      expected value for f, starting from a nearly neutral model of weak selection, and
      then assess the biological interpretation of this factor with evolutionary
      simulations. RESULTS: An expected value of f = 0.5 (i.e., equal dependency on the
      starting and ending states) is derived for sequences that are evolving under the
      nearly neutral model of this study. However, this expectation is sensitive to
      violations of its underlying assumptions as illustrated with the evolutionary
      simulations. CONCLUSION: This study illustrates how selection, drift, and
      mutation at the population level can be linked to the rate matrices of models for
      sequence evolution to derive an expected value of f. However, as f is affected by
      a number of factors that limit its biological interpretation, this factor should
      normally be estimated as a free parameter rather than fixed a priori in a +gwF
      analysis.

PMID- 15743517
TI  - Developmental changes in abundance of the VSPbeta protein following nuclear
      transformation of maize with the soybean vspbeta cDNA.
AB  - BACKGROUND: Developing monocots that accumulate more vegetative tissue protein is
      one strategy for improving nitrogen-sequestration and nutritive value of forage
      and silage crops. In soybeans (a dicotyledonous legume), the vspA and B genes
      encode subunits of a dimeric vegetative storage protein that plays an important
      role in nitrogen storage in vegetative tissues. Similar genes are found in
      monocots; however, they do not accumulate in leaves as storage proteins, and the
      ability of monocot leaves to support accumulation of an ectopically expressed
      soybean VSP is in question. To test this, transgenic maize (Zea Mays L. Hi-II
      hybrid) lines were created expressing soybean vspB from a maize ubiquitin Ubi-1
      promoter. RESULTS: From 81 bombardments, 101 plants were regenerated, and plants
      from five independent lines produced vspB transcripts and VSPbeta polypeptides.
      In leaves from seven-week-old plants (prior to flowering), VSPbeta accumulated to
      0.5% of the soluble leaf protein in primary transgenic plants (R0), but to only
      0.03% in R1 plants. During seed-filling (silage-stage) in R1 plants, the VSPbeta
      protein was no longer detected in leaves and stems despite continued presence of
      the vspB RNA. The RNA transcripts for this peptide either became less efficiently
      translated, or the VSPbeta protein became unstable during seed-fill. CONCLUSION:
      Developmental differences in the accumulation of soybean VSPbeta when
      transgenically expressed in maize show that despite no changes in the vspB
      transcript level, VSPbeta protein that is readily detected in leaves of
      preflowering plants, becomes undetectable as seeds begin to develop.

PMID- 15743519
TI  - Orientation determination by wavelets matching for 3D reconstruction of very
      noisy electron microscopic virus images.
AB  - BACKGROUND: In order to perform a 3D reconstruction of electron microscopic
      images of viruses, it is necessary to determine the orientation (Euler angels) of
      the 2D projections of the virus. The projections containing high resolution
      information are usually very noisy. This paper proposes a new method, based on
      weighted-projection matching in wavelet space for virus orientation
      determination. In order to speed the retrieval of the best match between
      projections from a model and real virus particle, a hierarchical correlation
      matching method is also proposed. RESULTS: A data set of 600 HSV-1 capsid
      particle images in different orientations was used to test the proposed method.
      An initial model of about 40 A resolutions was used to generate projections of an
      HSV-1 capsid. Results show that a significant improvement, in terms of accuracy
      and speed, is obtained for the initial orientation estimates of noisy herpes
      virus images. For the bacteriophage (P22), the proposed method gave the correct
      reconstruction compared to the model, while the classical method failed to
      resolve the correct orientations of the smooth spherical P22 viruses. CONCLUSION:
      This paper introduces a new method for orientation determination of low contrast
      images and highly noisy virus particles. This method is based on weighted
      projection matching in wavelet space, which increases the accuracy of the
      orientations. A hierarchical implementation of this method increases the speed of
      orientation determination. The estimated number of particles needed for a higher
      resolution reconstruction increased exponentially. For a 6 A resolution
      reconstruction of the HSV virus, 50,000 particles are necessary. The results show
      that the proposed method reduces the amount of data needed in a reconstruction by
      at least 50 %. This may result in savings 2 to 3 man-years invested in acquiring
      images from the microscope and data processing. Furthermore, the proposed method
      is able to determine orientations for some difficult particles like P22 with
      accuracy and consistency. Recently a low PH sindbis capsid was determined with
      the proposed method, where other methods based on the common line fail.

PMID- 15743521
TI  - Nanopores: maltoporin channel as a sensor for maltodextrin and lambda-phage.
AB  - BACKGROUND: To harvest nutrition from the outside bacteria e.g. E. coli developed
      in the outer cell wall a number of sophisticated channels called porins. One of
      them, maltoporin, is a passive specific channel for the maltodextrin uptake. This
      channel was also named LamB as the bacterial virus phage Lambda mis-uses this
      channel to recognise the bacteria. The first step is a reversible binding
      followed after a lag phase by DNA injection. To date little is known about the
      binding capacity and less on the DNA injection mechanism. To elucidate the
      mechanism and to show the sensitivity of our method we reconstituted maltoporin
      in planar lipid membranes. Application of an external transmembrane electric
      field causes an ion current across the channel. Maltoporin channel diameter is
      around a few Angstroem. At this size the ion current is extremely sensitive to
      any modification of the channels surface. Protein conformational changes,
      substrate binding etc will cause fluctuations reflecting the molecular
      interactions with the channel wall. The recent improvement in ion current
      fluctuation analysis allows now studying the interaction of solutes with the
      channel on a single molecular level. RESULTS: We could demonstrate the asymmetry
      of the bacterial phage Lambda binding to its natural receptor maltoporin.
      CONCLUSION: We suggest that this type of measurement can be used as a new type of
      biosensors.

PMID- 15743520
TI  - Angiogenesis in male breast cancer.
AB  - BACKGROUND: Male breast cancer is a rare but aggressive and devastating disease.
      This disease presents at a later stage and in a more advanced fashion than its
      female counterpart. The immunophenotype also appears to be distinct when compared
      to female breast cancer. Angiogenesis plays a permissive role in the development
      of a solid tumor and provides an avenue for nutrient exchange and waste removal.
      Recent scrutiny of angiogenesis in female breast cancer has shown it to be of
      significant prognostic value. It was hypothesized that this holds true in
      invasive ductal carcinoma of the male breast. In the context of male breast
      cancer, we investigated the relationship of survival and other clinico
      pathological variables to the microvascular density of the tumor tissue. METHODS:
      Seventy-five cases of primary male breast cancer were identified using the
      records of the Saskatchewan Cancer Agency over a period of 26 years. Forty-seven
      cases of invasive ductal carcinoma of the male breast had formalin-fixed paraffin
      embedded tissue blocks that were suitable for this study. All cases were
      reviewed. Immunohistochemical staining was performed for the angiogenic markers
      (cluster designations 31 (CD31), 34 (CD34) and 105 (CD105), von Willebrand factor
      (VWF), and vascular endothelial growth factor (VEGF)). Microvascular density
      (MVD) was determined using average, centre, and highest microvessel counts (AMC,
      CMC, and HMC, respectively). Statistical analyses compared differences in the
      distribution of survival times and times to relapse between levels of MVD, tumor
      size, node status and age at diagnosis. In addition, MVD values were compared
      within each marker, between each marker, and were also compared to clinico
      pathological data. RESULTS: Advanced age and tumor size were related to shorter
      survival times. There were no statistically significant differences in
      distributions of survival times and times to relapse between levels of MVD
      variables. There was no significant difference in MVD between levels of the
      different clinico-pathological variables. MVD was strongly and significantly
      correlated between AMC, CMC and HMC for CD31, CD34, and CD105 (p < 0.01) and
      remained moderate to weak for VWF and VEGF. CONCLUSION: Microvascular density
      does not appear to be an independent prognostic factor in male breast cancer.
      However, the likelihood of death for men with breast cancer is increased in the
      presence of increased age at diagnosis and advanced tumor size. This is perhaps
      linked to inherent tumor vasculature, which is strongly related throughout a
      tumor section.

PMID- 15743522
TI  - Reliability and validity of the AGREE instrument used by physical therapists in
      assessment of clinical practice guidelines.
AB  - BACKGROUND: The AGREE instrument has been validated for evaluating Clinical
      Practice Guidelines (CPG) pertaining to medical care. This study evaluated the
      reliability and validity of physical therapists using the AGREE to assess quality
      of CPGs relevant to physical therapy practice. METHODS: A total of 69 physical
      therapists participated and were classified as generalists, specialist or
      researchers. Pairs of appraisers within each category evaluated independently, a
      set of 6 CPG selected at random from a pool of 55 CPGs. RESULTS: Reliability
      between pairs of appraisers indicated low to high reliability depending on the
      domain and number of appraisers (0.17-0.81 for single appraiser; 0.30-0.96 when
      score averaged across a pair of appraisers). The highest reliability was achieved
      for Rigour of Development, which exceeded ICC> 0.79, if scores from pairs of
      appraisers were pooled. Adding more than 3 appraisers did not consistently
      improve reliability. Appraiser type did not determine reliability scores. End
      users, including study participants and a separate sample of 102 physical therapy
      students, found the AGREE useful to guide critical appraisal. The construct
      validity of the AGREE was supported in that expected differences on Rigour of
      Development domains were observed between expert panels versus those with
      no/uncertain expertise (differences of 10-21% p = 0.09-0.001). Factor analysis
      with varimax rotation, produced a 4-factor solution that was similar, although
      not in exact agreement with the AGREE Domains. Validity was also supported by the
      correlation observed (Kendall-tao = 0.69) between Overall Assessment and the
      Rigour of Development domain. CONCLUSION: These findings suggest that the AGREE
      instrument is reliable and valid when used by physiotherapists to assess the
      quality of CPG pertaining to physical therapy health services.

PMID- 15743523
TI  - Methodological bias in cluster randomised trials.
AB  - BACKGROUND: Cluster randomised trials can be susceptible to a range of
      methodological problems. These problems are not commonly recognised by many
      researchers. In this paper we discuss the issues that can lead to bias in cluster
      trials. METHODS: We used a sample of cluster randomised trials from a recent
      review and from a systematic review of hip protectors. We compared the mean age
      of participants between intervention groups in a sample of 'good' cluster trials
      with a sample of potentially biased trials. We also compared the effect sizes, in
      a funnel plot, between hip protector trials that used individual randomisation
      compared with those that used cluster randomisation. RESULTS: There is a tendency
      for cluster trials, with evidence methodological biases, to also show an age
      imbalance between treatment groups. In a funnel plot we show that all cluster
      trials show a large positive effect of hip protectors whilst individually
      randomised trials show a range of positive and negative effects, suggesting that
      cluster trials may be producing a biased estimate of effect. CONCLUSION:
      Methodological biases in the design and execution of cluster randomised trials is
      frequent. Some of these biases associated with the use of cluster designs can be
      avoided through careful attention to the design of cluster trials. Firstly, if
      possible, individual allocation should be used. Secondly, if cluster allocation
      is required, then ideally participants should be identified before random
      allocation of the clusters. Third, if prior identification is not possible, then
      an independent recruiter should be used to recruit participants.

PMID- 15743525
TI  - Retrovirology highlights a quarter century of HTLV-I research.
AB  - In 1977, Takatsuki and co-workers described in Japan a human malignant disease
      termed adult T-cell leukemia (ATL). Three years later, in 1980, Gallo and
      colleagues reported the identification of the first human retrovirus, human T
      cell leukemia virus type I (HTLV-I), in a patient with cutaneous T-cell lymphoma.
      This month, Retrovirology commemorates these two land mark findings by publishing
      separate personal recollections by Takatsuki and Gallo respectively on the
      discovery of ATL and HTLV.

PMID- 15743524
TI  - Effects of ICI 182780 on estrogen receptor expression, fluid absorption and sperm
      motility in the epididymis of the bonnet monkey.
AB  - BACKGROUND: The importance of estrogen in regulation of fluid absorption and
      sperm maturation in the rodent epididymis has been established from studies on
      estrogen receptor-alpha knockout mice. However, functional studies on the role of
      estrogen in primate epididymis have been few. The main objective of this study
      was therefore to extend these observations and systematically analyze the
      presence and function of estrogen receptors in modulating the function of the
      primate epididymis, using the bonnet monkey (Macaca radiata) as a model system.
      METHODS: A steroidal estrogen receptor (ER) antagonist, ICI 182780 (ICI), was
      administered to adult male bonnet monkeys via mini-osmotic pumps for a duration
      of 30 to 180 days. The expression of key estrogen-regulated genes (ER-alpha, Na-K
      ATPase alpha-1 and Aquaporin-1) was examined at specific time points. Further,
      the effect of ICI in modulating fluid reabsorption in efferent ductules was
      monitored, and critical sperm-maturation parameters were also analyzed. RESULTS:
      Our studies in the bonnet monkey revealed that both ER-alpha and ER-beta were
      expressed in all the three regions of the epididymis. We observed an increase in
      ER-alpha mRNA and protein in the caput of ICI-treated monkeys. Steady state mRNA
      levels of the water-channel protein, Aquaporin-1, was significantly lower in the
      caput of ICI-treated monkeys compared to controls, whereas the mRNA levels of Na
      K ATPase alpha-1 remained unchanged. In vitro incubation of efferent ductules
      with ICI resulted in two-fold increase in tubular diameter, indicating affected
      fluid reabsorption capacity. Furthermore, sperm from ICI-treated monkeys were
      immotile. CONCLUSION: Taken together, our results point to an integral role for
      estrogen in modulating the functions of the bonnet monkey epididymis. This study
      also demonstrates possible differences in the epididymal physiology of rodents
      and non-human primates, and thus underscores the significance of reports such as
      these, that examine the physiology of non-human primates (as opposed to rodents),
      in an attempt to understand similar events in the human.

PMID- 15743526
TI  - The discovery of the first human retrovirus: HTLV-1 and HTLV-2.
AB  - I describe here the history leading up to and including my laboratory's discovery
      of the first human retrovirus, HTLV-I, and its close relative, HTLV-II. My
      efforts were inspired by early work showing a retroviral etiology for leukemias
      in various animals, including non-human primates. My two main approaches were to
      develop criteria for and methods for detection of viral reverse transcriptase and
      to identify growth factors that could support the growth of hematopoietic cells.
      These efforts finally yielded success following the discovery of IL-2 and its use
      to culture adult T cell lymphoma/leukemia cells.

PMID- 15743528
TI  - Discovery of adult T-cell leukemia.
AB  - Adult T-cell leukemia (ATL) was first reported as a distinct clinical entity in
      1977 in Japan. The predominant physical findings are skin lesions,
      lymphadenopathy and hepatosplenomegaly. The ATL cells are of mature T-helper
      phenotype and have a characteristic appearance with indented nuclei. There is
      striking frequent hypercalcemia with increased numbers of osteoclasts. Central to
      the identification of the disease is a striking geographic clustering in
      southwestern Japan and the isolation of human T-cell lymphotropic virus type-1
      (HTLV-1) from the cell lines of patients. Worldwide epidemiological studies have
      been made through international collaborations. Several diseases were found to be
      related to HTLV-1 infection. Moreover, it was noted that an immunodeficiency
      state may be induced by HTLV-1 infection. In Japan, HTLV-1 carriers have been
      estimated to be 1.2 million, and more than 700 cases of ATL have been diagnosed
      each year.

PMID- 15743529
TI  - Survivin 2alpha: a novel Survivin splice variant expressed in human malignancies.
AB  - BACKGROUND: Survivin and its alternative splice forms are involved in critical
      cellular processes, including cell division and programmed cell death. Survivin
      is expressed in the majority of human cancers, but minimally in differentiated
      normal tissues. Expression levels correlate with tumor aggressiveness and
      resistance to therapy. RESULTS: In the present study, we identify and
      characterize a novel survivin isoform that we designate survivin 2alpha.
      Structurally, the transcript consists of 2 exons: exon 1 and exon 2, as well as a
      3' 197 bp region of intron 2. Acquisition of a new in-frame stop codon within
      intron 2 results in an open reading frame of 225 nucleotides, predicting a
      truncated 74 amino acid protein. Survivin 2alpha is expressed at high levels in
      several malignant cell lines and primary tumors. Functional assays show that
      survivin 2alpha attenuates the anti-apoptotic activity of survivin. Subcellular
      localization and immunoprecipitation of survivin 2alpha suggests a physical
      interaction with survivin. CONCLUSION: We characterized a novel survivin splice
      variant that we designated survivin 2alpha. We hypothesize that survivin 2alpha
      can alter the anti-apoptotic functions of survivin in malignant cells. Thus
      survivin 2alpha may be useful as a therapeutic tool in sensitizing chemoresistant
      tumor cells to chemotherapy.

PMID- 15743527
TI  - The role of the MAPK pathway alterations in GM-CSF modulated human neutrophil
      apoptosis with aging.
AB  - BACKGROUND: Neutrophils represent the first line of defence against aggressions.
      The programmed death of neutrophils is delayed by pro-inflammatory stimuli to
      ensure a proper resolution of the inflammation in time and place. The pro
      inflammatory stimuli include granulocyte-macrophage colony-stimulating factor (GM
      CSF). Recently, we have demonstrated that although neutrophils have an identical
      spontaneous apoptosis in elderly subjects compared to that in young subjects, the
      GM-CSF-induced delayed apoptosis is markedly diminished. The present study
      investigates whether an alteration of the GM-CSF stimulation of MAPKs play a role
      in the diminished rescue from apoptosis of PMN of elderly subjects. METHODS:
      Neutrophils were separated from healthy young and elderly donors satisfying the
      SENIEUR protocol. Neutrophils were stimulated with GM-CSF and inhibitors of the
      MAPKinase pathway. Apoptosis commitment, phosphorylation of signaling molecules,
      caspase-3 activities as well as expression of pro- and anti-apoptotic molecules
      were performed in this study. Data were analyzed using Student's two-tailed t
      test for independent means. Significance was set for p </= 0.05 unless stated
      otherwise. RESULTS: In this paper we present evidence that an alteration in the
      p42/p44 MAPK activation occurs in PMN of elderly subjects under GM-CSF
      stimulation and this plays a role in the decreased delay of apoptosis of PMN in
      elderly. We also show that p38 MAPK does not play a role in GM-CSF delayed
      apoptosis in PMN of any age-groups, while it participates to the spontaneous
      apoptosis. Our results also show that the alteration of the p42/p44 MAPK
      activation contributes to the inability of GM-CSF to decrease the caspase-3
      activation in PMN of elderly subjects. Moreover, GM-CSF converts the pro
      apoptotic phenotype to an anti-apoptotic phenotype by modulating the bcl-2 family
      members Bax and Bcl-xL in PMN of young subjects, while this does not occur in PMN
      of elderly. However, this modulation seems MAPK independent. CONCLUSION: Our
      results show that the alteration of p42/p44 MAPK activation contributes to the GM
      CSF induced decreased PMN rescue from apoptosis in elderly subjects. The
      modulation of MAPK activation in PMN of elderly subjects might help to restore
      the functionality of PMN with aging.

PMID- 15743530
TI  - Wearable kinesthetic system for capturing and classifying upper limb gesture in
      post-stroke rehabilitation.
AB  - BACKGROUND: Monitoring body kinematics has fundamental relevance in several
      biological and technical disciplines. In particular the possibility to exactly
      know the posture may furnish a main aid in rehabilitation topics. In the present
      work an innovative and unobtrusive garment able to detect the posture and the
      movement of the upper limb has been introduced, with particular care to its
      application in post stroke rehabilitation field by describing the integration of
      the prototype in a healthcare service. METHODS: This paper deals with the design,
      the development and implementation of a sensing garment, from the
      characterization of innovative comfortable and diffuse sensors we used to the
      methodologies employed to gather information on the posture and movement which
      derive from the entire garments. Several new algorithms devoted to the signal
      acquisition, the treatment and posture and gesture reconstruction are introduced
      and tested. RESULTS: Data obtained by means of the sensing garment are analyzed
      and compared with the ones recorded using a traditional movement tracking system.
      CONCLUSION: The main results treated in this work are summarized and remarked.
      The system was compared with a commercial movement tracking system (a set of
      electrogoniometers) and it performed the same accuracy in detecting upper limb
      postures and movements.

PMID- 15743531
TI  - PHACCS, an online tool for estimating the structure and diversity of uncultured
      viral communities using metagenomic information.
AB  - BACKGROUND: Phages, viruses that infect prokaryotes, are the most abundant
      microbes in the world. A major limitation to studying these viruses is the
      difficulty of cultivating the appropriate prokaryotic hosts. One way around this
      limitation is to directly clone and sequence shotgun libraries of uncultured
      viral communities (i.e., metagenomic analyses). PHACCS
      http://phage.sdsu.edu/phaccs, Phage Communities from Contig Spectrum, is an
      online bioinformatic tool to assess the biodiversity of uncultured viral
      communities. PHACCS uses the contig spectrum from shotgun DNA sequence assemblies
      to mathematically model the structure of viral communities and make predictions
      about diversity. RESULTS: PHACCS builds models of possible community structure
      using a modified Lander-Waterman algorithm to predict the underlying contig
      spectrum. PHACCS finds the most appropriate structure model by optimizing the
      model parameters until the predicted contig spectrum is as close as possible to
      the experimental one. This model is the basis for making estimates of uncultured
      viral community richness, evenness, diversity index and abundance of the most
      abundant genotype. CONCLUSION: PHACCS analysis of four different environmental
      phage communities suggests that the power law is an important rank-abundance form
      to describe uncultured viral community structure. The estimates support the fact
      that the four phage communities were extremely diverse and that phage community
      biodiversity and structure may be correlated with that of their hosts.

PMID- 15743532
TI  - Dengue fever: new paradigms for a changing epidemiology.
AB  - Dengue is the most important arthropod-borne viral disease of public health
      significance. Compared with nine reporting countries in the 1950s, today the
      geographic distribution includes more than 100 countries worldwide. Many of these
      had not reported dengue for 20 or more years and several have no known history of
      the disease. The World Health Organization estimates that more than 2.5 billion
      people are at risk of dengue infection. First recognised in the 1950s, it has
      become a leading cause of child mortality in several Asian and South American
      countries.This paper reviews the changing epidemiology of the disease, focusing
      on host and societal factors and drawing on national and regional journals as
      well as international publications. It does not include vaccine and vector
      issues. We have selected areas where the literature raises challenges to
      prevailing views and those that are key for improved service delivery in poor
      countries.Shifts in modal age, rural spread, and social and biological
      determinants of race- and sex-related susceptibility have major implications for
      health services. Behavioural risk factors, individual determinants of outcome and
      leading indicators of severe illness are poorly understood, compromising
      effectiveness of control programmes. Early detection and case management
      practices were noted as a critical factor for survival. Inadequacy of sound
      statistical methods compromised conclusions on case fatality or disease-specific
      mortality rates, especially since the data were often based on hospitalised
      patients who actively sought care in tertiary centres.Well-targeted operational
      research, such as population-based epidemiological studies with clear operational
      objectives, is urgently needed to make progress in control and prevention.

PMID- 15743533
TI  - BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic
      brain injury.
AB  - BACKGROUND: Mechanisms that affect recovery from fetal and neonatal hypoxic
      ischemic (H-I) brain injury have not been fully elucidated. The incidence of
      intrapartum asphyxia is approximately 2.5%, but the occurrence of adverse
      clinical outcome is much lower. One of the factors which may account for this
      relatively good outcome is the process of neurogenesis, which has been described
      in adult animals. We used a neonatal mouse model to assess new cells in the
      hippocampus after H-I injury. RESULTS: Neonatal mice underwent permanent
      unilateral carotid ligation on the seventh postnatal day followed by exposure to
      8% hypoxia for 75 minutes. The presence of new cells was determined by
      bromodeoxyuridine (BrdU) incorporation into cells with sacrifice of the animals
      at intervals. Brain sections were stained for BrdU in combination with neuronal,
      glial, endothelial and microglial stains. We found a significant increase in BrdU
      positive cells in the neonatal mouse hippocampus in the injured area compared to
      the non-injured area, most prominent in the dentate gyrus (DG) (154.5 +/- 59.6 v.
      92.9 +/- 32.7 at 3 days after injury; 68.9 +/- 23.4 v. 52.4 +/- 17.1 at 35 days
      after injury, p < 0.0011). Among the cells which showed differentiation, those
      which were stained as either microglial or endothelial cells showed a peak
      increase at three days after the injury in the DG, injured versus non-injured
      side (30.5 +/- 17.8 v. 2.7 +/- 2.6, p < 0.0002). As in the adult animal,
      neurogenesis was significantly increased in the DG with injury (15.0 +/- 4.6 v.
      5.2 +/- 1.6 at 35 days after injury, p < 0.0002), and this increase was
      subsequent to the appearance of the other dividing cells. Numbers of new
      oligodendrocytes were significantly higher in the DG on the non-injured side (7.0
      +/- 24.2 v. 0.1 +/- 0.3, p < 0.0002), suggesting that oligodendrocyte synthesis
      was reduced in the injured hippocampus. CONCLUSION: These findings demonstrate
      that the neonatal animal responds to brain injury with neurogenesis, much like
      the adult animal. In addition, H-I insult leads to more neurogenesis than hypoxia
      alone. This process may play a role in the recovery of the neonatal animal from H
      I insult, and if so, enhancement of the process may improve recovery.

PMID- 15743534
TI  - New York City HIV superbug: fear or fear not?
AB  - On February 11, 2005, the New York City Department of Health and Mental Hygiene
      announced that a city resident had recently been infected with a multi-drug
      resistant form of HIV and rapidly progressed to AIDS. The Health Commissioner,
      Thomas R. Frieden, called for increased vigilance against this new strain. Is
      this situation an emerging crisis or simply an unusual case report of rapid HIV
      progression?

PMID- 15743535
TI  - Modeling emergency department visit patterns for infectious disease complaints:
      results and application to disease surveillance.
AB  - BACKGROUND: Concern over bio-terrorism has led to recognition that traditional
      public health surveillance for specific conditions is unlikely to provide timely
      indication of some disease outbreaks, either naturally occurring or induced by a
      bioweapon. In non-traditional surveillance, the use of health care resources are
      monitored in "near real" time for the first signs of an outbreak, such as
      increases in emergency department (ED) visits for respiratory, gastrointestinal
      or neurological chief complaints (CC). METHODS: We collected ED CCs from 2/1/94 -
      5/31/02 as a training set. A first-order model was developed for each of seven CC
      categories by accounting for long-term, day-of-week, and seasonal effects. We
      assessed predictive performance on subsequent data from 6/1/02 - 5/31/03,
      compared CC counts to predictions and confidence limits, and identified anomalies
      (simulated and real). RESULTS: Each CC category exhibited significant day-of-week
      differences. For most categories, counts peaked on Monday. There were seasonal
      cycles in both respiratory and undifferentiated infection complaints and the
      season-to-season variability in peak date was summarized using a hierarchical
      model. For example, the average peak date for respiratory complaints was January
      22, with a season-to-season standard deviation of 12 days. This season-to-season
      variation makes it challenging to predict respiratory CCs so we focused our
      effort and discussion on prediction performance for this difficult category.
      Total ED visits increased over the study period by 4%, but respiratory complaints
      decreased by roughly 20%, illustrating that long-term averages in the data set
      need not reflect future behavior in data subsets. CONCLUSION: We found that ED
      CCs provided timely indicators for outbreaks. Our approach led to successful
      identification of a respiratory outbreak one-to-two weeks in advance of reports
      from the state-wide sentinel flu surveillance and of a reported increase in
      positive laboratory test results.

PMID- 15743536
TI  - On evolutionary origin of cancer.
AB  - BACKGROUND: The necessary and sufficient capabilities of cancer cell have been
      identified. Strikingly, this list does not include one that would seem to be a
      key property, namely the ability of cancer cells to kill their "host". This is
      believed to be a self-evident consequence of the other capabilities (e.g.,
      metastasis), although the available evidence suggests a distinct killer function.
      Taking into account this unlisted property can significantly affect the current
      paradigm of carcinogenesis. PRESENTATION OF THE HYPOTHESIS: On the assumption
      that killer function is a key capability of the cancer cell, it is suggested that
      cancer has evolved as a mechanism of negative selection of mutant alleles of
      vitally important genes present in population. Similarly to apoptosis, which is
      an altruistic suicidal act of a damaged cell, cancer is an altruistic suicidal
      act of an individual who carries dangerous alleles and presents a hazard for
      genetic stability of the population. From this point of view, apoptosis is not a
      protection means against cancer as generally believed, but rather they are the
      first and second lines of defense against genome instability, respectively.
      TESTING THE HYPOTHESIS: The modern DNA array technology is capable of revealing
      gene expression profiles responsible for killer function of cancer cell as well
      as those specific targets in the body that are most strongly affected by the
      tumor growth. IMPLICATIONS OF THE HYPOTHESIS: This hypothesis suggests new
      avenues of cancer research as well as principally new therapeutic strategies.

PMID- 15743538
TI  - Quality of sleep in patients with schizophrenia is associated with quality of
      life and coping.
AB  - BACKGROUND: While sleep disturbance is widespread in schizophrenia it is less
      clear whether sleep disturbance is uniquely related to impaired coping and
      perceived quality of life. METHODS: We simultaneously assessed sleep quality,
      symptoms, and coping in 29 persons with schizophrenia or schizoaffective disorder
      in a post acute phase of illness. Assessment instruments included the Pittsburgh
      Sleep Quality Index; the Positive and Negative Symptom Scale; the Heinrichs
      Quality of Life Scale; and the Ways of Coping Scale. Multiple regressions were
      performed predicting quality of life and coping from sleep quality controlling
      for age and symptom severity. On a subset of seven subjects non-dominant wrist
      actigraphy was used as an objective check of their self-reported poor sleep.
      RESULTS: Analyses revealed that poor sleep quality predicted low quality of life
      (r = -0.493; p = .022) and reduced preference for employing positive reappraisal
      when facing a stressor (r = -0.0594; p = 0.0012). Actigraphy confirmed poor sleep
      quality in a subset of subjects. They had shorter sleep duration (p < .0005),
      shorter average sleep episodes (p < .005) and more episodes of long awakening (p
      < 0.05) than community norms. CONCLUSION: The results are consistent with the
      hypotheses that poor sleep may play a unique role in sustaining poor quality of
      life and impaired coping in patients with schizophrenia. These associations may
      hold for community controls as well.

PMID- 15743537
TI  - Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy
      beverage compared with soy extract capsules in postmenopausal Thai women.
AB  - BACKGROUND: Isoflavones from soybeans may provide some beneficial impacts on
      postmenopausal health. The purpose of this study was to compare the
      pharmacokinetics and bioavailability of plasma isoflavones (daidzein and
      genistein) after a single dose of orally administered soy beverage and soy
      extract capsules in postmenopausal Thai women. METHODS: We conducted a randomized
      two-phase crossover pharmacokinetic study in 12 postmenopausal Thai women. In the
      first phase, each subject randomly received either 2 soy extract capsules
      (containing daidzin : genistin = 7.79 : 22.57 mg), or soy beverage prepared from
      15 g of soy flour (containing daidzin : genistin = 9.27 : 10.51 mg). In the
      second phase, the subjects received an alternative preparation in the same manner
      after a washout period of at least 1 week. Blood samples were collected
      immediately before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 32 h after
      administration of the soy preparation in each phase. Plasma daidzein and
      genistein concentrations were determined by using high performance liquid
      chromatography (HPLC). The pharmacokinetic parameters of daidzein and genistein,
      i.e. maximal plasma concentration (Cmax), time to maximal plasma concentration
      (Tmax), area under the plasma concentration-time curve (AUC) and half-life
      (t1/2), were estimated using the TopFit version 2.0 software with
      noncompartmental model analysis. RESULTS: There were no significant differences
      in the mean values of Cmax/dose, AUC0-32/dose, AUC0- proportional, variant/dose,
      Tmax, and t1/2 of genistein between both preparations. For pharmacokinetic
      parameters of daidzein, the mean values of Cmax/dose, Tmax, and t1/2 did not
      significantly differ between both preparations. Nonetheless, the mean AUC0
      32/dose and AUC0- proportional, variant/dose after administration of soy extract
      capsules were slightly (but significantly, p < 0.05) higher than those of soy
      beverage. CONCLUSION: The bioavailability of daidzein, which was adjusted for the
      administered dose (AUC/dose), following a single oral administration of soy
      beverage was slightly (but significantly) less than that of soy extract capsules,
      whereas, the bioavailability adjusted for administered dose of genistein from
      both soy preparations were comparable. The other pharmacokinetic parameters of
      daidzein and genistein, including Cmax adjusted for the dose, Tmax and t1/2, were
      not different between both soy preparations.

PMID- 15743539
TI  - Automated migration analysis based on cell texture: method & reliability.
AB  - BACKGROUND: In this paper, we present and validate a way to measure automatically
      the extent of cell migration based on automated examination of a series of
      digital photographs. It was designed specifically to identify the impact of
      Second Hand Smoke (SHS) on endothelial cell migration but has broader
      applications. The analysis has two stages: (1) preprocessing of image texture,
      and (2) migration analysis. RESULTS: The output is a graphic overlay that
      indicates the front lines of cell migration superimposed on each original image,
      with automated reporting of the distance traversed vs. time. Expert preference
      compares to manual placement of leading edge shows complete equivalence of
      automated vs. manual leading edge definition for cell migration measurement.
      CONCLUSION: Our method is indistinguishable from careful manual determinations of
      cell front lines, with the advantages of full automation, objectivity, and speed.

PMID- 15743541
TI  - JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of
      colorectal cancer in rats.
AB  - BACKGROUND: Epidemiological studies have shown that individuals who regularly
      consume NSAIDs have lower rates of mortality associated with colorectal cancer.
      Because COX-2 inhibitors prevent tumor growth through some mechanisms, we
      assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary
      metastases of colon cancer in a rat model. METHODS: A suspension of 5 x 10(6) RCN
      9 (rat colon cancer cells) was injected into the tail vein of 24 anesthetized
      male F344/DuCrj rats. Oral JTE-522 (0, 3, 10, or 30 mg/kg/day) was administered
      from the day before RCN-9 injection until the end of the study. Twenty-four days
      later, the lungs were removed from sacrificed rats and weighed. Pulmonary
      metastatic tumors were microscopically evaluated in the largest cross sections.
      We also performed immunohistochemical staining for both COX-2 and VEGF. RESULTS:
      JTE-522 dose-dependently decreased lung weight (p = 0.001) and the size of
      pulmonary metastatic tumors (p = 0.0002). However, the differences in the number
      of metastatic tumors among 4 groups were insignificant. Significant adverse
      effects of JTE-522 were undetectable. Immunohistochemical staining showed high
      levels of both COX-2 and VEGF in pulmonary metastatic tumors. CONCLUSION: JTE-522
      dose-dependently decreased the size, but not the number of pulmonary metastases.
      COX-2 inhibitors might block metastatic tumor growth, but not actual metastasis.
      Selective COX-2 inhibitors might be useful as therapeutic agents that inhibit the
      growth of metastatic tumors, as well as the tumorigenesis of colorectal cancer.

PMID- 15743540
TI  - Angiogenesis in cancer of unknown primary: clinicopathological study of CD34,
      VEGF and TSP-1.
AB  - BACKGROUND: Cancer of unknown primary remains a mallignancy of elusive biology
      and grim prognosis that lacks effective therapeutic options. We investigated
      angiogenesis in cancer of unknown primary to expand our knowledge on the biology
      of these tumors and identify potential therapeutic targets. METHODS: Paraffin
      embedded archival material from 81 patients diagnosed with CUP was used. Tumor
      histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous
      cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed
      immunohistochemically by use of specific monoclonal antibodies and was analyzed
      against clinicopathological data. RESULTS: VEGF expression was detected in all
      cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases
      and was strong in 20%. The expression of both proteins was not associated with
      any clinical or pathological parameters. Tumor MVD was higher in tumors
      classified as unfavorable compared to more favorable and was positively
      associated with VEGF and negatively with TSP-1. CONCLUSION: Angiogenesis is very
      active and expression of VEGF is almost universal in cancers of unknown primary.
      These findings support the clinical investigation of VEGF targeted therapy in
      this clinical setting.

PMID- 15743542
TI  - Topiramate for migraine prevention.

PMID- 15743543
TI  - Trigeminal neuralgia: diagnosis and treatment.
AB  - Trigeminal neuralgia is considered to be one of the most severe forms of pain in
      the human experience. In this discussion, classical neurology, current advances
      in medical science, and the relief of human suffering converge in a single nerve.
      Improvements in the resolution of neuroimaging have elucidated neurovascular
      relationships in striking detail. The availability of new antiepileptic
      medications has expanded the range of therapeutic options for patients whose pain
      cannot be controlled by first-line agents. Further developments in neurosurgical
      and radiosurgical techniques have provided effective treatments with increasingly
      wider margins of safety. Significant advances in cortical stimulation technology
      are also making headway into pain relief and delineating the central mechanisms
      of chronic neuropathic pain.

PMID- 15743546
TI  - Cluster headache: diagnosis and treatment.
AB  - Cluster headache is a primary headache syndrome that is under-diagnosed and in
      many instances under-treated. The pain produced during a cluster headache is more
      severe than that generated by any other primary headache. Cluster headache is
      very stereotyped in its presentation and fairly easy to diagnose with an in-depth
      headache history. Cluster headache is easy to treat in most individuals if the
      correct medications are used and the correct dosages are given. The following
      manuscript presents information on the clinical presentation of cluster headache
      and both medicinal and surgical interventions.

PMID- 15743544
TI  - Migraine headache: options for acute treatment.
AB  - The optimal acute treatment of migraine requires recognition of the multitude of
      migraine presentations, the frequency of total attacks, and number of days of
      headache disability. These initial diagnostic steps are initiated in the waiting
      room, but phase-specific and stratified treatment selection requires having
      mutual understanding, trust, and belief through extensive discussion. The
      imperative acute treatment goal must be to treat early, but not too often, a fact
      represented by a 75% or better occurrence of pain freedom at 2 hours with two or
      fewer drug doses averaging 2 or fewer days a week. Migraine-specific therapy best
      wins the race against time and allodynia. Employing this formulary, multiple
      triptan formulations and phase and stratified patient-centered therapy creates
      success.

PMID- 15743545
TI  - Menstrual migraine.
AB  - Migraine is a common disorder that is disproportionately prevalent in women,
      especially during the reproductive years. Hormonal changes may play a role in the
      etiology of migraine, as many women note that their migraine attacks occur in
      temporal relationship with their menses. The Headache Classification Subcommittee
      of the International Headache Society has recently defined menstrual and
      menstrually related migraine. We review the most relevant and recent literature
      on menstrual migraine, with a special focus on pathophysiology and therapy.
      Although the pathogenesis of menstrual and menstrually related migraine is not
      well understood, estrogen withdrawal seems to play an important role as a trigger
      for menstrual migraine attacks. The therapeutic approach also may differ from the
      treatment of nonmenstrual migraine. Some patients do not require prophylaxis when
      they can abort their attacks effectively, whereas others may benefit from
      perimenstrual prophylaxis or standard migraine prophylaxis.

PMID- 15743547
TI  - New insights into childhood ependymomas.
AB  - Childhood ependymomas, which comprise approximately 10% to 15% of all brain
      tumors arising in patients less than 18 years of age, remain a highly problematic
      group of tumors to treat. Relapse-free survival rates vary significantly in
      contemporary series, and therapeutic approaches remain unsettled.

PMID- 15743549
TI  - Advances in the assessment of childhood brain tumors and treatment-related
      sequelae.
AB  - The assessment of children with brain tumors represents a unique challenge due to
      the difficulty in obtaining repeat tissue samples for evaluation. Over the past
      decade, magnetic resonance imaging has been the standard imaging modality
      utilized to follow tumor status and treatment effects in these children because
      of its sensitivity and ability to delineate tumor tissue. The information
      obtained from standard magnetic resonance imaging is primarily limited to
      structural changes. Newer techniques that noninvasively assess metabolic and
      physiologic characteristics of brain and tumor tissue are being developed and
      incorporated into clinical trials, particularly for the newer molecularly
      targeted agents, where physiologic changes rather than tumor size reduction may
      be an early determinant of activity. This article reviews some of these
      techniques and their role in the assessment of children with brain tumors.

PMID- 15743548
TI  - Tools for diagnosis of leukodystrophies and other disorders presenting with white
      matter disease.
AB  - Advances in biochemical techniques, molecular genetics, and neuroimaging,
      particularly magnetic resonance imaging, have made possible the diagnosis of a
      significant proportion of leukodystrophies. A specific diagnosis allows the
      physician to give prognostic information, monitor for known complications, and
      ultimately may allow disease specific therapeutics. The purpose of this review is
      to familiarize the reader with pertinent tools in the diagnosis of
      leukodystrophies and other white matter disorders that may present with white
      matter disease. The first section discusses conditions that may mimic
      leukodystrophy and how to exclude them. Although not meant to be an exhaustive
      summary, several key disorders and their clinical, biochemical, and neuroimaging
      features are presented. The second section focuses on classically described
      leukodystrophies and their diagnosis. Finally, a third section provides a
      diagnostic algorithm to help the clinician in the diagnosis of the patient with
      leukodystrophy.

PMID- 15743550
TI  - Seizures and metabolic disease.
AB  - Seizures represent an important clinical manifestation of inborn errors of
      metabolism. The presence of myoclonic seizures and very early onset are clues to
      a metabolic disorder. Specific correlations between age of seizure onset and
      electroencephalogram patterns with inborn errors of metabolism are discussed. The
      explosion of information in neurogenetics and metabolism mandates increasing
      awareness of appropriate metabolic diagnostic and therapeutic strategies in the
      setting of certain epilepsies. Specific laboratory, imaging, and treatment
      considerations are included to present updated material in a field that continues
      to expand rapidly.

PMID- 15743551
TI  - Ropinirole in the treatment of restless legs syndrome.

PMID- 15743552
TI  - Fatigue in multiple sclerosis: a rational approach to evaluation and treatment.
AB  - With the publication of the Multiple Sclerosis Council Guideline on the
      management of multiple sclerosis (MS) fatigue, there has been increased
      appreciation for the role fatigue can play in MS. Secondary fatigue is fatigue
      caused by other etiologies than those directly related to MS. Once these causes
      are ruled out, fatigue is related to MS. Secondary MS-related fatigue comes as
      result of the symptoms of MS that drain energy. Once secondary MS causes are
      ruled out, then the patient is deemed as having primary MS fatigue. Fatigue
      management is both nonpharmacologic and pharmacologic. Occupational therapists
      are the major allied health providers that address the role fatigue plays in MS
      patients. Over the past two decades, numerous clinical trials have been conducted
      on drugs for treating MS-related fatigue. Of these agents, amantadine has been
      studied for the longest period, and has shown efficacy in about one third of
      patients with MS-related fatigue on several commonly used scales. Two randomized 
      trials of the central nervous system stimulant pemoline have yielded unimpressive
      results; efficacy was seen at higher doses but coupled with an unacceptable risk
      of adverse events. The wake-promoting agent modafinil is the only agent to show
      efficacy compared with placebo on the Fatigue Severity Scale, a measure that is
      highly resistant to "impulse answering" and is thus viewed as one of the most
      difficult scales on which to show -benefit. This article reviews fatigue in MS
      and proposes a rational strategy for evaluation and management of this most
      common MS symptom.

PMID- 15743553
TI  - Neuromuscular disorders and sleep.
AB  - Neuromuscular disorders are caused by the primary involvement of the motor unit.
      In these patients, sleep-disordered breathing (SDB) due to respiratory muscle
      weakness is often encountered during sleep. Because there is a tendency to
      overlook this disorder, all patients with neuromuscular disorders should be
      questioned about SDB. Overnight polysomnography is the best investigation for SDB
      and nocturnal desaturations. In the management of these patients, noninvasive
      intermittent positive pressure ventilation results in improvement of SDB and
      breathing.

PMID- 15743554
TI  - Sleep-related violence.
AB  - Most violent behaviors arise from wakefulness. It is important to realize that
      violent behaviors that may have forensic science implications can arise from the
      sleep period. By virtue of the fact that these behaviors arise from sleep, they
      are executed without conscious awareness, and, therefore, without culpability.
      The most common underlying conditions arising from sleep are disorders of arousal
      (sleepwalking and sleep terrors), the rapid eye movement sleep behavior disorder,
      and nocturnal seizures. In addition, there are a number of psychiatric conditions
      (dissociative disorders, malingering, and Munchausen syndrome by proxy) that
      actually arise from periods of wakefulness occurring during the sleep period. The
      clinical and medico-legal evaluation of such cases is outlined, and should be
      performed by a multidisciplinary team of experienced sleep medicine
      practitioners.

PMID- 15743555
TI  - [Facilitated angioplasty: neither black nor white].

PMID- 15743556
TI  - [Adenosine in ventricular arrhythmias: moving towards new pathophysiologic
      frontiers].

PMID- 15743557
TI  - [Biomechanical factors: influence on cardiovascular function].

PMID- 15743559
TI  - [Study of post-infarction coronary perfusion using quantitative analysis of
      myocardial echocardiography with intravenous injection of contrast].
AB  - INTRODUCTION AND OBJECTIVES: After a myocardial infarction, damage to the
      microcirculation indicates a worse prognosis. We compared the usefulness of the
      quantitative analysis of myocardial contrast echocardiography with intravenous
      injection of contrast (MCE-iv) with intracoronary injection (MCE-ic) for
      analyzing coronary perfusion. PATIENTS AND METHOD: We studied 42 patients with a
      first ST-elevation myocardial infarction, single-vessel disease and a patent
      artery (TIMI 3, stenosis < 50%). Myocardial perfusion in segments in the infarct
      related area was quantified (normalized scale 0-1) with MCE-ic (bolus of
      Levovist, real-time imaging, perfusion considered normal if > 0.75) and MCE-iv
      (perfusion of SonoVue, single-image capture in 1 out of each 6 cycles with
      trigger set at end-systole, perfusion considered normal if > 0.9). Perfusion was
      considered abnormal if 2 or more segments showed altered perfusion. RESULTS:
      Quantification with MCE-iv took 5 +/- 1 minutes. No side effects were observed.
      MCE-ic was normal in 141 segments (80%) out of 176 segments included in the
      infarcted area, whereas 35 segments (20%) showed abnormal perfusion. MCE-ic was
      normal in 31 patients (74%) and was altered in 11 cases (26%). Normal perfusion
      with MCE-iv had a sensitivity of 91%, a specificity of 84% and a kappa index of
      0.67 for predicting normal perfusion with MCE-ic (r = 0.86; P < .0001 between the
      two techniques). CONCLUSIONS: In comparison with MCE-ic, quantitative analysis of
      single images captured during intravenous perfusion of contrast is an easy, rapid
      and valid method for analyzing postinfarction coronary perfusion.

PMID- 15743558
TI  - [Analysis with the propensity score of the association between likelihood of
      treatment and event of interest in observational studies. An example with
      myocardial reperfusion].
AB  - INTRODUCTION AND OBJECTIVES: Analysis of the effect of treatment in observational
      studies is complex due to differences between treated and nontreated patients.
      Calculating the probability of receiving treatment conditioned on relevant
      covariates (propensity score [PS]) has been proposed as a method to control for
      these differences. We report an application of PS to assess the association
      between reperfusion treatment and 28-day case fatality in patients with acute
      myocardial infarction (AMI). METHOD: We describe the procedure used to calculate
      PS for receiving reperfusion treatment, and different strategies to analyze the
      association between PS and case fatality with regression modeling and matching.
      Data were from a population-based registry of 6307 patients with AMI in Spain
      during 1997-98. RESULTS: The PS for reperfusion was calculated in 5622 patients.
      In the multivariate analysis, reperfusion was associated with lower case fatality
      (OR = 0.59; 95% confidence interval [95% CI]: 0.46-0.77). When PS was included as
      a covariate, this association became non- significant (OR = 0.76; 95% CI: 0.57
      1.01). In the subgroup of matched patients with a similar PS (n = 3138),
      treatment was not associated with case fatality (OR = 0.95; 95% CI: 0.72-1.26).
      When the influence of cases with missing data on PS was controlled for,
      reperfusion treatment was associated with lower fatality (OR = 0.66; 95% CI: 0.55
      0.80). CONCLUSIONS: Calculating propensity score is a method that controls for
      differences between treated and nontreated patients. This score has limitations
      when matching is incomplete and when data are missing. Results of the present
      example suggest that reperfusion treatment reduces AMI case fatality.

PMID- 15743560
TI  - [Drug-eluting stents in patients with left main coronary lesions who are not
      candidates for surgical revascularization].
AB  - INTRODUCTION AND OBJECTIVES: Surgical revascularization is the treatment of
      choice in patients with left main coronary artery stenosis. Conventional stents
      are not a valid alternative because of the rate of restenosis and sudden cardiac
      death. Drug-eluting stents, which reduce the rate of restenosis, may represent an
      alternative to cardiac surgery. The objective of this study was to describe the
      results with drug-eluting stents in patients with left main coronary artery
      stenosis who were poor candidates for surgical revascularization. PATIENTS AND
      METHOD: We prospectively followed a consecutive series of patients who were poor
      candidates for surgical revascularization and were treated with implantation of a
      drug-eluting stent in the left main coronary artery between May 2002 and April
      2004. In-hospital and long-term results were analyzed. Follow-up included
      angiographic and intravascular ultrasound (IVUS) studies. RESULTS: Forty-two
      patients (25 men, 59.5%) with a mean age of 70.1 (10.5) years were studied.
      Fourteen (33%) had diabetes, and 7 (16.7%) had a protected left main coronary
      artery. The reasons for ruling out surgery were poor distal vessels in 19
      (45.2%), previous surgery in 9 (21.4%), age in 6 (14.3%), primary angioplasty in
      5 (11.4%), and other reasons in 3 (7.2%). Four patients (9.5%) died before
      discharge, three of them after primary angioplasty. No in-hospital
      revascularization procedures were needed. Median follow-up time was 288 days;
      mean follow-up time was 315 (241) days. Another four patients died after
      discharge (9.5%) on days 5, 24, 34 and 115. Angioplasty was repeated in one
      patient, and another was referred for heart transplantation. CONCLUSIONS: Drug
      eluting stents represent a valid alternative in patients with left main coronary
      artery stenosis who are poor candidates for surgical revascularization.
      Randomized studies with a longer follow-up should be performed to evaluate their
      benefits in patients eligible for surgery.

PMID- 15743561
TI  - [Clinical, echocardiographic and prognostic profile of Streptococcus viridans
      left-sided endocarditis].
AB  - INTRODUCTION AND OBJECTIVES: Published case series on Streptococcus viridans
      endocarditis are scarce and outdated. The aims of our study were multiple: to
      analyze the profile of the Streptococcus viridans endocarditis, to compare it
      with other types of left-sided endocarditis and with cases caused by
      Staphylococcus aureus, and to determine predictors of poor outcome in
      Streptococcus viridans endocarditis. PATIENTS AND METHOD: We analyzed 441
      episodes of endocarditis: 330 left-sided and 54 caused by Streptococcus viridans
      (16%). We compared the 54 cases due to Streptococcus viridans with the remaining
      cases of left-sided endocarditis in our series, and also with cases caused by
      Staphylococcus aureus. We also analyzed the predictors of death and urgent
      surgery in Streptococcus viridans endocarditis. RESULTS: Left-sided endocarditis
      due to Streptococcus viridans led to a similar degree of valvular destruction,
      showed acute onset less frequently, and led to less renal failure, septic shock
      and mortality than the remaining cases of left-sided endocarditis in our series.
      The same differences were found in comparison to Streptococcus viridans
      endocarditis. Prognostic factors for Streptococcus viridans left-sided
      endocarditis were heart failure and periannular complications. CONCLUSIONS:
      Although Streptococcus viridans is a nonaggressive microorganism, valvular
      destruction is similar to that caused by other pathogens when it causes left
      sided endocarditis. Nonetheless its prognosis is better, a feature which may be
      related to the fact that the systemic infectious syndrome can be treated more
      effectively. Prognostic factors in left-sided endocarditis due to Streptococcus
      viridans are heart failure and periannular complications.

PMID- 15743562
TI  - [Early and late effects of adenosine in experimental ventricular tachycardia].
AB  - INTRODUCTION AND OBJECTIVE: To study the action of adenosine in experimental
      ventricular tachycardia. MATERIAL AND METHOD: We studied 173 mongrel dogs
      weighing 13-17 kg anesthetized with 30 mg/kg sodium pentobarbital given
      intravenously. Myocardial lesions were provoked with the injection of 1-1.5 mL
      phenol in the free wall of the left ventricle. Ventricular arrhythmia was induced
      30 min later with aconitine crystals inserted into the periphery of the damaged
      area. The potential early and delayed antiarrhythmic action of adenosine was
      systematically investigated in 85 animals. Leads DII, aVR and aVL, unipolar right
      and left intraventricular leads, and one unipolar lead on the wall of the
      superior vena cava were used to record control tracings and tracings in the
      presence of myocardial damage during ventricular tachycardia and after injection
      of the drug. RESULTS: Sinus rhythm did not reappear in 72 control animals that
      did not receive adenosine. In the 63 animals with aconitine-induced ventricular
      tachycardia associated to myocardial damage, the optimal response to 6 mg
      adenosine-early and fleeting sinus rhythm-was seen in 45% of the dogs; delayed
      sinus rhythm was seen in 5%. In 67% of the 18 animals with ventricular
      tachycardia due only to myocardial damage, early and late sinus rhythm appeared
      with doses of 6 and 12 mg, and late sinus rhythm was seen with a dose of 12 mg.
      CONCLUSIONS: The antiarrhythmic action of adenosine was seen not only in
      ventricular tachycardia due to aconitine (triggered activity), but also in
      tachycardia induced by the myocardial damage (microreentries).

PMID- 15743563
TI  - [Regional differences in viscosity, elasticity and wall buffering function in
      systemic arteries: pulse wave analysis of the arterial pressure-diameter
      relationship].
AB  - INTRODUCTION AND OBJECTIVES: Regional variations in the incidence of vascular
      diseases have been related to regional differences in arterial viscoelasticity.
      The aim of this study was to characterize the differences in the elastic and
      viscous modulus and in wall buffering function between central and peripheral
      systemic arteries, through a time-series analysis of the pressure-diameter
      relationship. MATERIAL AND METHOD: Pressure and diameter were measured in seven
      arterial segments (carotid, brachiocephalic trunk, ascending aorta, proximal,
      middle and distal descending thoracic aorta, and femoral artery) from six sheep.
      Each segment was mounted on an in vitro mock circulatory system and perfused with
      Tyrode solution, with a pulse frequency of 1.8 Hz and systemic pressure levels.
      We used the Kelvin-Voigt model to calculate the pressure-diameter elastic (Epd,
      mmHg/mm) and viscous (Vpd, mmHg.s/mm) modulus, and to quantify the local wall
      buffering function (Vpd/Epd). We also calculated the incremental Young's and
      pressure-strain elastic modulus and pulse wave velocity for each segment.
      RESULTS: The elastic and viscous modulus increased from proximal to distal
      segments. The wall buffering function did not differ significantly between
      arteries. The lower rigidity of the central arteries compared to the distal ones
      may indicate that the systolic arterial compliance function is concentrated in
      the central arterial segments. On the other hand, the greater viscosity in the
      distal segments may indicate that viscous energy loss is concentrated in these
      segments. CONCLUSIONS: Arterial elasticity and viscosity can be interpreted as
      properties that are dependent on the region of the vessel, whereas wall buffering
      function can be considered region-independent.

PMID- 15743564
TI  - [Guidelines on management (diagnosis and treatment) of syncope. Update 2004.
      Executive summary].

PMID- 15743565
TI  - [Coronary revascularization. State of the art].

PMID- 15743566
TI  - [Coronary revascularization: clinical features and indications].
AB  - Coronary artery revascularization is an established therapeutic intervention and
      is therefore included in all treatment guidelines for patients with coronary
      artery disease. Although the procedure has been available for more than 40 years,
      constant technical progress in surgical and percutaneous revascularization
      continues to bring the benefits of revascularization therapy to new groups of
      patients. Therefore the indications and limitations of this approach need to be
      reviewed and updated periodically. The aim of revascularization therapy is to
      improve the prognosis or symptoms and quality of life in patients with ischemic
      heart disease. The revascularization process comprises two aspects: 1) indication
      and selection of the revascularization procedure, and 2) performance of the
      procedure. Involvement of the clinical cardiologist in the first step is
      fundamental. Basing their decisions on clinical, functional and anatomical
      features, these professionals detect and select patients who would benefit, and
      also help to select the revascularization technique. In this Update article on
      revascularization we review, for stable ischemic heart disease and non-ST segment
      elevation acute coronary syndromes, the following: 1) the most relevant aspects
      to consider when evaluating the need for and the type of revascularization (age,
      sex, diabetes, renal function, electrocardiographic changes, ventricular function
      and quantification of functional relevance of coronary artery disease and
      viability of the acinetic areas); 2) indications for surgical or percutaneous
      intervention, and the choice of therapeutic strategy according to the latest
      clinical evidence and guidelines of scientific societies, and 3) currently
      available data on the controversy regarding choice of the revascularization
      procedure in patients with multivessel disease.

PMID- 15743567
TI  - [An adult with a double-chamber right ventricle].

PMID- 15743568
TI  - [Systolic ventricular dysfunction, a new marker of coronary artery disease in
      patients with aortic stenosis without previous myocardial infarction].
AB  - Identification of clinical factors associated with coronary artery disease could
      obviate the need for coronary angiography in selected patients with severe aortic
      stenosis. We studied 315 patients (68 [8] years) with severe aortic stenosis
      without previous infarction who underwent coronary angiography. In the univariate
      analysis, age (P = .001), dyslipidemia (P = .003), angina (P = .018), aortic
      gradient (P = .001) and reduced ejection fraction (P = .006) were predictors of
      coronary artery disease. After multivariate analysis, age (OR = 1.079, P = .01),
      ejection fraction < 40% (OR = 2.685, P = .02), angina (OR = 2.518, P = .04) and
      dyslipidemia (OR = 2.34, P = .008) were the factors independently associated with
      coronary artery disease. Left ventricular dysfunction correlated independently
      with the presence of coronary artery disease.

PMID- 15743569
TI  - [Percutaneous treatment of atrial septal aneurysm].
AB  - Among a total number of 203 patients with atrial septal defects (ASD) or patent
      foramen ovale (PFO) who were treated by percutaneous closure, we selected 29 (19
      with ASD and 10 with PFO) who fulfilled the criteria for atrial septal aneurysm.
      Eight patients had functional class II or III dyspnea, and 12 had a history of
      previous cerebrovascular accident (38%). Seven of the patients with ASD, had a
      single defect and 12 had multiple defects; 14 received a single occluder and 5
      patients needed 2 or 3 devices. Follow-up transthoracic ultrasound study at 6
      months showed the defect to be successfully closed in all 29 patients. After a
      mean follow-up time of 31 +/- 19 months, all patients were alive and symptom
      free. Patients with atrial septal aneurysm and associated ASD or PFO can be
      successfully treated with Amplatzer septal occluders.

PMID- 15743571
TI  - [Complete atrioventricular block secondary to pulmonary embolism].
AB  - We describe a 73-year-old woman with a history of breast cancer and metastatic
      disease diagnosed in January 2002 (stable when we saw her) who was admitted for
      sudden dyspnea and presyncope. Complete atrioventricular block was documented,
      and a temporary pacemaker was implanted. Eight hours after admission she
      recovered sinus rhythm with left bundle branch block as seen in previous
      recordings. Computed tomography showed bilateral pulmonary thromboembolism. An
      electrophysiological study showed normal atrioventricular conduction. We suggest
      that in this patient, who had previous left bundle branch block, pulmonary
      thromboembolism may have induced transient right bundle branch block, which in
      turn caused atrioventricular block.

PMID- 15743570
TI  - [Spontaneous pneumopericardium in a patient with community-acquired pneumonia].
AB  - Pneumopericardium is an uncommon but potentially serious condition. It appears in
      association with invasive diagnostic and therapeutic procedures, although cases
      have also been reported in association with bronchospasm, esophageal disorders,
      and other problems. We describe a case of spontaneous pneumopericardium with
      chest pain in a patient with community-acquired pneumonia.

PMID- 15743572
TI  - [Hepatitis C and HIV in Spanish prisons].

PMID- 15743573
TI  - [Predictive markers of HIV and HCV infection and co-infection among inmates in a
      Spanish prison].
AB  - OBJECTIVE: To study the prevalence and factors associated with HIV and HCV
      infection among inmates of a Spanish prison. METHOD: A cross-sectional study was
      carried out in July 2001. We determined HCV (ELISA and RIBA-3) and HIV (ELISA and
      Western-blot) serology in the prison population. Study variables included age,
      sex, nationality and previous intravenous drug use (IDU). In IDU inmates we
      analyzed the age when intravenous drug use was initiated, years of consumption,
      age at first admission in prison and syringe sharing with other inmates. The
      subpopulations of Arab and Romani (gypsy) inmates were studied differentially.
      RESULTS: A total of 800 inmates (mean age 34.2 6 6.2 years) were evaluated; 74.3%
      were Spanish and 33.6% IDU. HCV serology was obtained in 730 inmates and HIV
      serology in 773 with the following seroprevalence results: HCV 38.2%, HIV 19.1%
      and HCV-HIV co-infection 18.8%. The variables associated with HCV or HIV
      infection in the univariate analysis were Spanish nationality, previous IDU and
      coinfection by the other virus. In the multivariate analysis, only coinfection
      and, particularly, previous IDU (HCV infection: adjusted ORp 104.8 [95% CI: 49.4
      222.2]) (HIV infection adjusted ORp 45.1 [95% CI: 14.0-144.9]) maintained an
      association with the two infections. CONCLUSIONS: The prevalence of HIV and HCV
      infection and coinfection is high in Spanish prisons. Infection by either of
      these viruses and previous IDU were independently associated with both
      infections. The percentage of non-Spanish inmates with these infections is low.

PMID- 15743574
TI  - [Evaluation of the Robobact system for processing stool cultures: another step
      towards automation in the microbiology laboratory].
AB  - OBJECTIVE: The objective of this study was to evaluate the Robobact system
      (DIESSE Diagnostica Senese S.p.A., Italy) for processing stool specimens and to
      compare it with conventional methodology. METHOD: A total of 240 stool specimens
      from outpatients in Madrid (Spain) were studied. The samples were processed
      simultaneously with both the Robobact system and a conventional method. RESULTS:
      Overall, 13 isolates of Campylobacter spp., 12 of Salmonella spp., 4 of Yersinia
      enterocolitica and 1 of Shigella spp. were obtained. The Robobact method failed
      to identify 1 of the 13 Campylobacter spp. isolates and 2 of the 12 Salmonella
      spp. isolates. The single Shigella spp. isolate was detected only by the Robobact
      system. All the Robobact results were available at 24 hours. CONCLUSIONS:
      Robobact is a fast, useful tool for microbiological processing of stool
      specimens.

PMID- 15743575
TI  - [Nocardiosis and bronchiectasis. An uncommon association?].
AB  - OBJECTIVE: Nocardiosis is difficult to diagnose and infrequently associated with
      bronchiectasis or cystic fibrosis. This study analyzes the clinical and
      microbiological characteristics of 40 patients in whom microorganisms belonging
      to the Nocardia asteroides complex were isolated. METHODS: We studied 27 males
      and 13 females, with a mean age of 45 years (8-82). Nocardia spp. were isolated
      in 129 samples. Cultures were performed with conventional methods; additionally,
      when branching Gram-positive bacilli were visualized on microscopic examination,
      modified BCYE-alpha (m) medium was used. RESULTS: In 77.5% of the cases,
      investigation for Nocardia spp. was based on microscopy findings, in six patients
      it was a fortuitous finding in BCYE-alpha (m) medium, and in only three patients
      nocardiosis was clinically suspected. Twenty-five patients had nocardiosis (5
      disseminated infection and 20 lung infection) and the remaining 15 were
      colonized. The most frequent risk factor in the infections, whether disseminated
      or not, was systemic glucocorticoid use (P 5 .001). The most frequent underlying
      pathology was bronchiectasis (80%), associated or not with cystic fibrosis. There
      were seven deaths and two patients had neurological sequelae. CONCLUSIONS:
      Bronchiectasis was an important risk factor for colonization by Nocardia spp. (P
      5 0.01) in all the patients studied, and for infection (P 5 0.05) in patients
      without cystic fibrosis. The use of BCYE-alpha (m) medium in processing
      respiratory secretions highly facilitated the isolation of Nocardia spp.

PMID- 15743576
TI  - [Activity of ertapenem and 19 other antimicrobial agents against beta-lactam
      resistant Streptococcus pneumoniae and Haemophilus influenzae respiratory tract
      isolates].
AB  - INTRODUCTION: Ertapenem is a new carbapenem with a long half-life that has a
      broad spectrum of action against Gram-positive and Gram-negative bacteria.
      Although, clinically indicated for the treatment of the polymicrobial abdominal
      infection, other uses are possible, due to the broad spectrum of action of this
      antimicrobial agent. OBJECTIVE: The purpose of this study was to examine the
      susceptibility to ertapenem of Streptococcus pneumoniae and Haemophilus
      influenzae strains with resistance to beta-lactam antibiotics. METHODS: The study
      comprised 105 S. pneumoniae strains with a reduced susceptibility to penicillin
      G, 86 S. pneumoniae strains resistant to penicillin, and 100 H. influenzae
      strains resistant to ampicillin isolated fron clinical respiratory samples
      collected in the 21 participating microbiology laboratories. Susceptibility to
      antimicrobials was tested using an agar dilution method. RESULTS: The S.
      pneumoniae strains with intermediate resistance to penicillin were highly
      susceptible to carbapenems, with MIC90 of 0,25 and 0,5 mg/l for imipenem and
      ertapenem, respectively. Among the penicillin-resistant strains the MIC90 values
      for imipenem and ertapenem were 1 and 2 mg/l respectively. Carbapenems were very
      active against the whole group of H. influenzae strains, particullary ertapenem,
      which inhibited 90% of the series at a concentration of 0,12 mg/l. CONCLUSIONS:
      Ertapenem is a powerful agent against the most common respiratory bacterial
      pathogens, including those with resistance mechanisms effective against other
      compouunds. Few strains can currently be considered resistant to this carbapenem,
      which is at least comparable to imipenem, cefotaxime or the modern
      fluorquinolones. Such performance, and its favorable pharmacokinetic
      characteristics, make ertapenem an interesting option for the treatment of
      respiratory tract infections.

PMID- 15743577
TI  - [Spondylodiscitis and sacroiliitis due to Streptococcus agalactiae in adults:
      clinical case and literature review].
AB  - INTRODUCTION: Streptococcus agalactiae is a well-known pathogen related with
      infection in newborns, and in women during pregnancy and the puerperium. In
      recent years it has been described as a causal agent in invasive disease in
      immunodepressed adults and those with other severe underlying pathologies.
      METHODS: We describe a case of S. agalactiae spondylodiscitis and concomitant
      bilateral sacroiliitis in an adult with no known underlying diseases. A
      systematic review of the related literature was performed (MEDLINE and EMBASE, up
      to December 2003). RESULTS: The literature search retrieved only 33 cases of
      spondylodiscitis (predominance in men, 55-70 years old) and 13 cases of
      sacroiliitis (higher frequency in women, 30-40 years old) due to S. agalactiae.
      Simultaneous involvement of both locations of the axial skeleton is unusual.
      CONCLUSION: Spondylodiscitis and sacroiliitis due to S. agalactiae is uncommon.
      S. agalactiae is an emerging pathogen in adults outside of the gestational and
      perinatal period. This micro-organism produces spondylodiscitis in the adult
      population over 50 years old. In contrast, sacroiliac involvement is described
      mainly in women in the reproductive age.

PMID- 15743578
TI  - [Expanded-spectrum beta-lactamase-producing strains of E. coli: origin,
      characteristics and incidence in Southern Alicante (Spain) in the period 1999
      2003].
AB  - INTRODUCTION: In the last years, we have verified the increasing emergence of
      bacteria, specially Escherichia coli, that produce expanded spectrum beta
      lactamases (ESBL), enzymes which confer resistance to all cephalosporins (except
      cephamycins) and aztreonam. These bacteria are frequently resistant also to non
      beta-lactam antibiotics, a fact which poses an important clinical problem.
      METHODS: Descriptive study of ESBL-producing strains of E. coli isolated in all
      kind of specimens in two hospitals of Southern Alicante (Spain), throughout a
      period of 57 months (January 1999 to September 2003), paying a close attention to
      their origin (outpatients or admitted patients), co-resistance to non beta-lactam
      antibiotics and evolution of their incidence. RESULTS: Respectively, 3% and 2.25%
      of E. coli strains isolated in each hospital produce ESBL (3.83% and 2.85% of
      strains from admitted and 2.74% and 2.1% from outpatients). 30.73% and 24.58% of
      strains ESBL were isolated in admitted patients. We found in both hospitals much
      higher percentages of co-resistance to ciprofloxacin, gentamicin and trimetoprim
      sulfamethoxazole in ESBL-producing strains. CONCLUSION: The percentage of ESBL
      producing E. coli is high in our environment, but it is even more noteworthy its
      clear trend to increase. It is very remarkable the high percentage of ESBL
      producing strains isolated from outpatients. Finally, we emphasize the high
      percentages of co-resistance to non-beta-lactam antibiotics.

PMID- 15743580
TI  - [Antimicrobial resistance and bacterial virulence].
AB  - Hospitals are places with high selective pressure by antimicrobial agents. For
      this reason, bacteria producing nosocomial infections need to be not only
      virulent, but also resistant to antimicrobial agents. In the present review we
      analyse the effect of the acquisition of an antibiotic resistance phenotype in
      bacterial fitness and virulence. Besides that, we review as well the existence of
      common mechanisms for resistance to antimicrobial agents and bacterial virulence.
      In this line, we highlight the role of multidrug efflux pumps on bacterial
      virulence. Since opportunistic pathogens frequently have an environmental origin,
      we also discuss the role of natural ecosystems, as well as their potential
      contamination, on the selection of bacteria resistant to antimicrobial agents.

PMID- 15743579
TI  - [Significance of hepatitis B core antibody as the only marker of hepatitis B
      infection].
AB  - INTRODUCTION: Little is known about the clinical significance of the "anti-HBc
      alone" serological profile (absence of HBsAg and anti-HBs) in HBV infections. The
      objective of the present study was to estimate the prevalence of the anti-HBc
      alone immunological profile and the clinical-epidemiological characteristics of
      patients with this profile. METHODS: Prospective, cross-sectional, descriptive
      study performed in 2002 and including patients with anti-HBc alone (HBsAg
      negative, anti-HBs-negative and anti-HBc-positive). All the cases identified
      underwent the following microbiological tests: IgM anti-HBc, HBeAg, anti-HBe,
      anti-HDV, anti-HCV, anti-HIV, as well as HBV-DNA testing by qualitative nested
      PCR. Furthermore, studies of serum biochemical parameters, blood counts and
      coagulation, as well as a clinical-epidemiological interview were performed in
      all patients. RESULTS: Among 3900 patients studied, 195 (5%) presented the anti
      HBc alone profile (48% were > 65 years old). Residual anti-HBs (< 10 mUI/mL) was
      found in 44% of cases and 33% were anti-HBe positive. HCV or HIV coinfection were
      seen in 38% and 8%, respectively. HBV-DNA was detected in 4.2% (5/120) of cases.
      Epidemiologically, detection of anti-HBc alone was casual in 60% of patients,
      whereas the remaining cases had a history of chronic liver disease (82% of these
      were anti-HCV positive). In a high percentage (63%) the transmission mechanism of
      HBV infection was unknown (11% intravenous drug abuser, 10% surgery, 6%
      transfusions). CONCLUSION: The anti-HBc alone pattern is a frequent finding,
      particularly in patients > 65 years old and in HCV or HIV coinfected patients.
      Although HBV-DNA was detected in a small percentage of cases, this test could be
      indicated in certain clinical situations (liver disease, coinfection, donors).
      Furthermore, this profile seems to be related with HCV infection; hence, we
      consider anti-HCV detection necessary in all patients with anti-HBc alone.

PMID- 15743581
TI  - [Ticks (Acarina: Ixodidae) as vectors and reservoirs of pathogen microorganisms
      in Spain].
AB  - Hard and soft-ticks are obligate haematophagous arachnids of medical and
      veterinary significance mainly because of the animal disease agents transmitted
      by them, which include an array of different pathogens (virus, bacteria, protozoa
      and nematodes). Ticks transmit microbes by several routes including salivary
      secretions, coxal fluids, regurgitation and faeces. Among the biological factors
      that contribute to the high vector potential of ticks are their living habits and
      characteristic properties of their saliva secretions and blood digestion. In the
      Iberian Peninsula, the prostriata tick Ixodes ricinus, and the metastriata
      Dermacentor marginatus, Rhipicephalus sanguineus and Hyalomma marginatum are the
      main species that could bite man, and are involved in the transmission of
      Borrelia burgdorferi sensu lato, several genoespecies of Rickettsia (R. conorii,
      R. slovaca, R. aeschlimannii) and Anaplasma phagocytophila.

PMID- 15743582
TI  - [A 42-year-old man with fever and lumbar pain].

PMID- 15743583
TI  - [Soft tissue tumor and fever in a patient with myelodysplastic syndrome].

PMID- 15743584
TI  - [Retroperitoneal parasitation by a vermiform organism in a patient from Africa].

PMID- 15743585
TI  - [Treatment of extrahospital pneumonia and home hospitalization].

PMID- 15743586
TI  - [Primary Streptococcus suis meningitis: first case in humans described in Latin
      America].

PMID- 15743587
TI  - [Ochrobactrum anthropi infectious endocarditis in an immunocompetent patient].

PMID- 15743588
TI  - [Biochemical bone markers and bone mass study in recently postmenopausal women
      without osteoporosis].
AB  - BACKGROUND AND OBJECTIVE: To date, there have not been performed enough studies
      in Spain to analyze the usefulness of biochemical bone markers in postmenopausal
      and non-osteoporotic women. POPULATION AND METHOD: We studied several groups of
      women, ages between 17 and 30 years, 30-45 years, premenopausal and recently
      postmenopausal in order to know the reference values of some biochemical bone
      markers along 2 years in premenopausal and postmenopausal women (postmenopausal
      divided in 2 groups: those under treatment with ordinary hormonal replacement
      therapy [HRT], and those without it). RESULTS: Values of biochemical bone markers
      were higher in postmenopausal and in 17-30 years group than in premenopausal and
      30-45 years group (p < 0.05). Absolute values and the change in bone markers (%)
      were higher in postmenopausal and non-osteoporotic women under HRT than in those
      without HRT (% change: OC, 35,72 vs 4.45 [p < 0.01]; ALPo, 13,13 vs 27.06 [p <
      0.01]; NTx, 42.74 vs 10.93 [p < 0.01]; fDPD, 21.07 vs 28.49 [p < 0.05];
      betaCrossLaps, 50,17 vs 23.04 [p < 0.01]). CONCLUSIONS: We have defined reference
      values in our region and have proved that biochemical bone markers (absolute
      values and their change from the basal value) represent a useful tool in
      monitoring hormonal replacement therapy in recently postmenopausal and non
      osteoporotic women.

PMID- 15743589
TI  - [Health related problems as cause of visits to hospital emergency departments].
AB  - BACKGROUND AND OBJECTIVE: Medication-related problems (MRPs) are health problems
      resulting from patient pharmacotherapy failure that interfere with the expected
      outcome in the patient's health status. The aim of this study was to discover the
      health problems associated with the appearance of MRPs. PATIENTS AND METHOD:
      Patient interviews, together with the assessment of medical records were the
      sources of information used in the assessment and identification of MRPs. A
      validated questionnaire was used for the interviews; in order to classify the
      health problems found, the ICD-9 was used. RESULTS: 2,556 patients were
      interviewed over a period of one year at a hospital emergency department. 2,261
      of these cases were valid. Osteoarticular diseases, poorly defined signs and
      symptoms of illness, injuries and intoxications were the disorders most commonly
      associated with the appearance of MRPs. MRPs of necessity and effectiveness had a
      similar profile. MRPs of safety were more commonly associated with poorly defined
      signs and symptoms of illness, injuries and intoxications, as well as nervous,
      digestive and blood problems. CONCLUSIONS: Most frequent medication related
      health problems causing visits to hospital emergency departments were
      osteoarticular disorders, followed by poorly defined signs and symptoms of
      illness. Differences were observed in the diagnoses between the different
      dimensions and types of MRP.

PMID- 15743590
TI  - [Lung rounded atelectasis. A benign lesion due to asbestos].
AB  - BACKGROUND AND OBJECTIVE: Rounded atelectasis (RA) is an unusual form of
      pulmonary lesion often confounded with pulmonary neoplasia. We studied the main
      diagnostic and evolutive characteristics of a series of patients diagnosed with
      RA. PATIENTS AND METHOD: Twenty patients diagnosed of RA in a tertiary hospital
      in Catalonia were included in the study. The diagnostic criterion of RA was
      strictly based on thoracic CT. Clinical data and pulmonary function tests were
      also evaluated. Four teen patients underwent a long term follow-up. RESULTS:
      Asbestos was the cause of RA in 13 cases (65%); 7 had previously had homolateral
      pleural effusion; 5 pulmonary tuberculosis and in 1 case RA appeared at the lung
      biopsy site. The most frequent localization was inferior lobes and left side
      (70%). Eighteen patients had a ventilatory disorder: 10 restrictive, 6 mixed and
      2 obstructive. In no case, RA evolved to malignancy. CONCLUSIONS: RA is a benign
      lesion mainly due to asbestos showing well-defined morphological characteristics.

PMID- 15743592
TI  - [Drug related problems].

PMID- 15743591
TI  - [Osteoporosis: the problem of its definition].

PMID- 15743593
TI  - [The unique judgement in multicenter clinical trials: the new Spanish normative
      in the European frame].

PMID- 15743594
TI  - [Endoscopic ultrasonography and pancreatic cystic lesions].

PMID- 15743595
TI  - [Radiation therapy with synchrotron radiation and cisplatin-based chemotherapy as
      a treatment of gliomas].
AB  - The application of synchrotron radiation in medicine dates back to more than one
      decade. In particular, a team of researchers led by Dr. F. Esteve has been
      working for several years in the Grenoble Synchrotron (ESRF) on radiotherapy
      treatments to heal brain tumors. The team has recently obtained a very promising
      new result. Gliomas the commonest brain tumor in the adult and the mean survival
      in advanced disease patients is lower than one year. Conventional radiation
      therapy is used palliatively since it is one of the most radiotherapy-resistant
      tumors. Moreover, chemotherapy and surgery have no utility in most cases.
      Experiments at the Grenoble Synchrotron have been carried out in mice with
      gliomas and they consist of injecting cysplatine into the tumors so that an
      intense monochromatic radiation is applied afterwards. Half-life of sick
      untreated mice is 28 days. With the use of cysplatine alone, it expands to 48
      days. However, the association of two treatments supposes a half-life of 206 days
      (six times greater than in untreated mice). After one year of treatment, 34% of
      animals remain alive, which constitutes a result never seen before in this type
      of radio-resistant tumors.

PMID- 15743596
TI  - [Analysis of TCR-gamma gene rearragement in patients with mycosis fungoides].

PMID- 15743597
TI  - [Physicians have the most influence on patient satisfaction. Study of 471 cases].

PMID- 15743599
TI  - [Impact factor of Spanish biomedical journals].

PMID- 15743600
TI  - [Early mortality in patients with community-acquired bacteremia].

PMID- 15743602
TI  - [Significance of functional status in mortality of hospitalized elderly people].

PMID- 15743604
TI  - [Comments on noncompaction cardiomyopathy].

PMID- 15743605
TI  - Visual processing of targets can reduce saccadic latencies.
AB  - Normal human saccadic reaction times (SRTs) have been thought to be approximately
      200 ms. The present study, using an experimental method that takes advantage of
      what the saccade system has evolved to do (by instructing subjects to rapidly
      acquire detailed visual information from the environment), shows that human SRTs
      are actually on the order of 150 ms. Moreover, when combined with the sensory
      based "gap" effect (removal of gaze fixation object prior to target
      presentation), this method yielded extremely low SRTs. These findings imply that
      previous approximations of human SRTs may have been too conservative, and that
      the group of saccades often classified as "express" may instead represent the
      norm.

PMID- 15743606
TI  - Aftereffect of adaptation to Glass patterns.
AB  - Our visual systems constantly adapt their representation of the environment to
      match the prevailing input. Adaptation phenomena provide striking examples of
      perceptual plasticity and offer valuable insight into the mechanisms of sensory
      coding. Here, we describe an aftereffect of adaptation to a spatially structured
      image whereby an unstructured test stimulus takes on illusory structure locally
      perpendicular to that of the adaptor. Objective measurement of the strength of
      the aftereffect for different patterns suggests a neural locus of adaptation
      prior to the extraction of complex form in the visual processing hierarchy,
      probably at the level of primary visual cortex. This view is supported by further
      experiments showing that the aftereffect exhibits partial interocular transfer
      but complete transfer across opposite contrast polarities. However, the
      aftereffect does show weak position invariance, suggesting that adaptation at
      higher levels of the visual system may also contribute to the effect.

PMID- 15743607
TI  - Greater depth seen with phantom stereopsis is coded at the early stages of visual
      processing.
AB  - A visual search task was used to investigate the spatially parallel coding of
      depth from binocular disparity and from binocularly unmatched features.
      Experiment 1, using disparity noise, showed that detectability is higher for
      illusory phantom targets defined by unmatched features than for disparity-defined
      targets, although the two targets were equated as to theoretically minimum depth.
      Experiment 2, using binocularly unmatched noise whose width was equal to the
      disparity of the noise used in Experiment 1, showed that noise severely
      interferes with the detection of both the disparity and the phantom targets.
      These results are consistent with the idea that the greater depth seen with
      phantom stereopsis is coded at the early stages of visual processing.

PMID- 15743608
TI  - Contributions of local orientation and position features to shape integration.
AB  - Contour integration plays an important role in linking local elements into global
      shape and the binding strength among local elements depends on both orientation
      and position features. The very high sensitivity reported for detecting the
      sinusoidal deformation of circular contours may result from the presence and
      concordance of both orientation and position cues to shape difference. In this
      study, position and orientation-defined micropatch-sampled radial frequency
      (MSRF) patterns were employed, which permit the independent assessment of the
      contributions of local orientation and position features to shape integration. It
      was demonstrated that, while both local orientation and position features can
      encode shape deformation, the human visual system is more sensitive to
      orientation-defined shape difference than to position-defined shape difference.
      Furthermore, integration of the local orientation feature into shape is more than
      two times stronger than that of local position, and may involve a global pooling
      mechanism. Nevertheless, optimal shape discrimination performance requires the
      analysis of both local orientation and position features.

PMID- 15743609
TI  - Spatial interference among moving targets.
AB  - Peripheral vision for static form is limited both by reduced spatial acuity and
      by interference among adjacent features ('crowding'). However, the visibility of
      acuity-corrected image motion is relatively constant across the visual field. We
      measured whether spatial interference among nearby moving elements is similarly
      invariant of retinal eccentricity and assessed if motion integration could
      account for any observed sensitivity loss. We report that sensitivity to the
      direction of motion of a central target-highly visible in isolation-was strongly
      impaired by four drifting flanking elements. The extent of spatial interference
      increased with eccentricity. Random-direction flanks and flanks whose directions
      formed global patterns of rotation or expansion were more disruptive than flanks
      forming global patterns of translation, regardless of the relative direction of
      the target element. Spatial interference was low-pass tuned for spatial frequency
      and broadly tuned for temporal frequency. We show that these results challenge
      the generality of models of spatial interference that are based on retinal image
      quality, masking, confusions between target and flanks, attentional resolution
      limits or (simple) "averaging" of element parameters. Instead, the results
      suggest that spatial interference is a consequence of the integration of
      meaningful image structure within large receptive fields. The underlying
      connectivity of this integration favours low spatial frequency structure but is
      broadly tuned for speed.

PMID- 15743610
TI  - Learning letter identification in peripheral vision.
AB  - Performance for a variety of visual tasks improves with practice. The purpose of
      this study was to determine the nature of the processes underlying perceptual
      learning of identifying letters in peripheral vision. To do so, we tracked
      changes in contrast thresholds for identifying single letters presented at 10
      degrees in the inferior visual field, over a period of six consecutive days. The
      letters (26 lowercase Times-Roman letters, subtending 1.7 degrees) were embedded
      within static two-dimensional Gaussian luminance noise, with rms contrast ranging
      from 0% (no noise) to 20%. We also measured the observers' response consistency
      using a double-pass method on days 1, 3 and 6, by testing two additional blocks
      on each of these days at luminance noise of 3% and 20%. These additional blocks
      were the exact replicates of the corresponding block at the same noise contrast
      that was tested on the same day. We analyzed our results using both the linear
      amplifier model (LAM) and the perceptual template model (PTM). Our results showed
      that following six days of training, the overall reduction (improvement across
      all noise levels) in contrast threshold for our seven observers averaged 21.6%
      (range: 17.2-31%). Despite fundamental differences between LAM and PTM, both
      models show that learning leads to an improvement of the perceptual template
      (filter) such that the template is more capable of extracting the crucial
      information from the signal. Results from both the PTM analysis and the double
      pass experiment imply that the stimulus-dependent component of the internal noise
      does not change with learning.

PMID- 15743611
TI  - The watercolor effect: quantitative evidence for luminance-dependent mechanisms
      of long-range color assimilation.
AB  - When a dark chromatic contour delineating a figure is flanked on the inside by a
      brighter chromatic contour, the brighter color will spread into the entire
      enclosed area. This is known as the watercolor effect (WCE). Here we quantified
      the effect of color spreading using both color-matching and hue-cancellation
      tasks. Over a wide range of stimulus chromaticities, there was a reliable shift
      in color appearance that closely followed the direction of the inducing contour.
      When the contours were equated in luminance, the WCE was still present, but weak.
      The magnitude of the color spreading increased with increases in luminance
      contrast between the two contours. Additionally, as the luminance contrast
      between the contours increased, the chromaticity of the induced color more
      closely resembled that of the inside contour. The results support the hypothesis
      that the WCE is mediated by luminance-dependent mechanisms of long-range color
      assimilation.

PMID- 15743612
TI  - Chromatic properties of the colour-shading effect.
AB  - The 'colour-shading effect' describes the phenomenon whereby chromatic variations
      affect the magnitude of perceived shape-from-shading in luminance patterns. A
      previous study showed that in mixed colour-plus-luminance sine-wave plaids,
      impressions of depth in the luminance component were enhanced by non-aligned
      chromatic components, and suppressed by aligned chromatic components [Nature
      Neuroscience 6 (2003) 641-644]. Here we examine the chromatic determinants of
      these effects. Colour contrast was defined along the cardinal axes of colour
      space in order to isolate the L-M and S-(L+M) post-receptoral chromatic
      mechanisms. We found no difference in the potency of L-M-only and S-(L+M)-only
      gratings, either for enhancing or suppressing perceived depth. Moreover, the
      magnitude of depth-suppression was no different for any combination of depth
      enhancing and depth-suppressing cardinal directions. Finally we tested whether
      the visual system carried the assumption that natural shading is tinged with
      blue, by measuring perceived depth in a colour-plus-luminance grating that was
      made to appear either bright-yellow/dark-blue or bright-blue/dark-yellow. However
      there was no difference in the magnitude of depth-suppression between conditions,
      suggesting that the visual system does not make any assumption about the colour
      of natural shading. Taken together, the results suggest that while the colour
      shading effect is highly sensitive to colour contrast, it is agnostic with
      respect to colour direction.

PMID- 15743613
TI  - The optomotor response: a robust first-line visual screening method for mice.
AB  - In both scotopic and photopic conditions, the rotation of a grating was found to
      elicit head movements in mice. The highest spatial frequency eliciting this
      optomotor response provided an estimate of visual acuity. In male C57BL/6J mice,
      visual acuity increased from 0.26cpd in scotopic conditions to 0.52cpd in
      photopic conditions whereas it was 0.52 cpd in both sets of conditions in
      129/SvPas mice. No optomotor response was detected in albino CD1 mice and rd1
      retinal degeneration mice although light sensitivity in CD1 mice was attested by
      photophobia and normal electroretinograms. This rapid and cheap method could
      provide a powerful test of visual performance in genetically modified and
      pharmacologically treated mice.

PMID- 15743614
TI  - Changes in visual motion perception before saccadic eye movements.
AB  - Execution of a saccadic eye movement influences subsequent motion perception
      [Park, J., Lee, J., & Lee, C. (2001). Non-veridical visual motion perception
      immediately after saccades. Vision Research, 41, 3751-3761]. In the current
      study, we determined the pattern of perceptual changes for visual motion
      presented before saccades. The accuracy of judging the direction of a moving
      target was variable depending on the direction of target motion. Based on the
      pattern of judgment errors, the direction associated with no error, or DNE, could
      be defined. When a moving target was seen by stationary eyes, the DNE was roughly
      vertical, and the perceptual judgment for adjacent directions was biased away
      from the vertical direction. When the same visual motion was seen before
      horizontal saccades, the DNE shifted in the direction of the impending saccade,
      and the perceptual judgment of adjacent directions was shifted away from the new
      DNE, thus, shifting the perceived direction of the vertical in the direction
      opposite to the saccade. These changes improved the accuracy of direction
      judgment for visual motion in the visual field ipsiversive to impending saccades.
      In addition to shift of the DNE, perceptual judgment for oblique directions
      became near veridical before saccades, which we call the anti-oblique effect.
      These results suggest that motion perception is dynamically and anisotropically
      modulated at the time of saccades, and the DNE shift may be a part of processes
      dynamically reallocating computational resources, improving perceptual
      performance in advance for sensory events to be acquired by impending saccades.

PMID- 15743615
TI  - The time course of visual processing: backward masking and natural scene
      categorisation.
AB  - Human observers are very good at deciding whether briefly flashed novel images
      contain an animal and previous work has shown that the underlying visual
      processing can be performed in under 150 ms. Here we used a masking paradigm to
      determine how information accumulates over time during such high-level
      categorisation tasks. As the delay between test image and mask is increased, both
      behavioural accuracy and differential ERP amplitude rapidly increase to reach
      asymptotic levels around 40-60 ms. Such results imply that processing at each
      stage in the visual system is remarkably rapid, with information accumulating
      almost continuously following the onset of activation.

PMID- 15743616
TI  - Spatial interactions in amblyopia: effects of stimulus parameters and amblyopia
      type.
AB  - Adults with amblyopia were recently shown to perform abnormally in tasks
      requiring integration of local features into global percepts. Moreover, spatial
      interactions in amblyopic patients, though often found to be abnormal, showed
      marked variability. Here we measured collinear lateral interactions using Gabor
      patches in a large number of amblyopic (N=75) and normal subjects (N=25), testing
      four spatial frequencies (1.5, 3, 6, 9 cpd). We used the lateral masking
      paradigm, in which the contrast-detection threshold is measured in the presence
      of high-contrast flankers at different distances from a central target. Whereas
      in normal subjects spatial interaction patterns were evident across all spatial
      frequencies, amblyopic subjects showed abnormal spatial interactions and
      increasing deficiencies with increasing spatial frequencies. These abnormalities
      depended on the axis of astigmatism (in meridional amblyopia) and were more
      pronounced in strabismic than in anisometropic amblyopia. Spatial interactions
      were independent on the contrast-detection thresholds. Thus, adults with
      amblyopia might perform as well as normal observers for some stimulus parameters
      and abnormally for others. Our results indicate a close relationship between
      abnormal visual input to the visual cortex during development and abnormal
      functionality of the collinear spatial interactions in adults with amblyopia.

PMID- 15743617
TI  - Differential aging of chromatic and achromatic visual pathways: behavior and
      electrophysiology.
AB  - Aging of visual pathways was measured psychophysically and physiologically in
      subjects aged 20-89 years. Contrast thresholds for the chromatic pathways
      increased with age, but there were no significant changes for thresholds of the
      achromatic pathway at low spatial frequencies. For visual evoked potential (VEP)
      responses, again only the chromatic pathways were significantly affected by age.
      Age-related changes in chromatic responses were not apparent when stimuli were
      adjusted by age-related contrast thresholds. This suggests that the chromatic and
      achromatic visual pathways age differently and that the VEP accurately and
      objectively reflects behavioral changes with age.

PMID- 15743618
TI  - Comparative study of laboratory-scale thermophilic and mesophilic activated
      sludge processes.
AB  - Laboratory-scale mesophilic (20-35 degrees C) and thermophilic (55 degrees C)
      activated sludge processes (ASPs) treating diluted molasses wastewater were
      compared in effluent quality, removal of different COD fractions, sludge yield,
      floc size, and sludge settleability. The effect of polyaluminium chloride (PAC)
      with high cationic charge on sludge settleability and effluent quality was also
      studied. In the ASPs, the hydraulic retention time was 12h in both processes,
      corresponding to a volumetric loading rate of 3.2+/-1.0 kg COD(filt) m(-3)d(-1).
      The mesophilic ASP gave 79+/-18% and 90+/-2% and the thermophilic ASP gave 50+/
      6% and 67+/-11% total COD (COD(tot)) and GF/A-filtered COD (COD(filt)) removals,
      respectively. The higher COD values in the thermophilic effluent were due to
      dispersed particles, such as free bacteria, measured as colloidal COD
      (COD(col)=difference between soluble COD (COD(sol)) and COD(filt)). Both ASPs
      gave high (90%) COD(sol) removals. Aeration (24-h) of the thermophilic ASP
      effluent at 35 degrees C reduced the density of the free bacteria by half, which
      was also measured as 90% COD(col) removal. Post-aeration of thermophilic effluent
      at 55 degrees C had no influence either on the density of free bacteria or on the
      COD(col) values. The use of PAC did not increase COD(tot) or COD(filt) removals
      in either process, but reduced the mesophilic and increased the thermophilic
      sludge volume index values.

PMID- 15743619
TI  - Phosphorus-discharge hysteresis during storm events along a river catchment: the
      River Swale, UK.
AB  - Variations in the concentration of determinands in rivers during storms often
      result in a hysteresis effect with different concentration during the rising and
      falling limb of the hydrograph. This is investigated here by measuring total
      phosphorus, particulate phosphorus and soluble reactive phosphorus at 3-h
      intervals at three points along the River Swale. Phosphorus concentration
      discharge hysteresis from 10 storm events were quantified using an empirical
      model. The size and direction of the hysteresis loops were described by a
      response factor, and the slope of the loop quantified by a gradient constant. The
      modelled loops produced acceptable agreement with the field measurements.
      Hysteresis patterns for all phosphorus fractions changed markedly downstream,
      with predominantly anticlockwise trajectories in the upland moors (indicating a
      slow diffuse phosphorus delivery to the river) and clockwise in the intensively
      farmed lowland (indicating mobilisation of within-channel and riverbank
      phosphorus, and rapid inputs from field drains). The size of the hysteresis loops
      increased downstream, indicating an increased capacity for phosphorus storage and
      mobilisation within the lower catchment. During a succession of storms, lowland
      hysteresis loops decreased in magnitude, tending towards anticlockwise behaviour,
      indicating a depletion of mobile phosphorus from the river channel and margins.
      The modelling of hysteresis trajectories offers a convenient method of
      determining the relative contributions of diffuse and within-channel phosphorus
      sources.

PMID- 15743620
TI  - Chemical reactions between arsenic and zero-valent iron in water.
AB  - Batch experiments and X-ray photoelectron spectroscopic (XPS) analyses were
      performed to study the reactions between arsenate [As(V)], arsenite [As(III)] and
      zero-valent iron [Fe(0)]. The As(III) removal rate was higher than that for As(V)
      when iron filings (80-120 mesh) were mixed with arsenic solutions purged with
      nitrogen gas in the pH range of 4-7. XPS spectra of the reacted iron coupons
      showed the reduction of As(III) to As(0). Soluble As(III) was formed when As(V)
      reacted with Fe(0) under anoxic conditions. However, no As(0) was detected on the
      iron coupons after 5 days of reaction in the As(V)-Fe(0) system. The removal of
      the arsenic species by Fe(0) was attributed to electrochemical reduction of
      As(III) to sparsely soluble As(0) and adsorption of As(III) and As(V) to iron
      hydroxides formed on the Fe(0) surface under anoxic conditions. When the
      solutions were open to atmospheric air, the removal rates of As(V) and As(III)
      were much higher than under the anoxic conditions, and As(V) removal was faster
      than As(III). The rapid removal of As(III) and As(V) was caused by adsorption on
      ferric hydroxides formed readily through oxidation of Fe(0) by dissolved oxygen.

PMID- 15743621
TI  - Anaerobic treatment of azo dye Acid Orange 7 under fed-batch and continuous
      conditions.
AB  - Acid Orange 7 (AO7) was treated anaerobically under fed-batch and continuous
      conditions. Fed-batch assays carried out with and without cosubstrate showed that
      the removal rate of this dye is highly favourable when glucose is added as
      cosubstrate. In addition, some intermediates generated after the reductive
      breakdown of AO7, such as 1-amino-2-naphthol (1A2N), seem to play a significant
      role as redox mediators, thus increasing the degradation rate of the dye. This
      effect is evidenced by the fact that, during the first feeding, the maximum AO7
      removal rate was achieved after a lag phase, whereas for further AO7 feedings
      this phase was not observed. This can be explained by the presence of 1-amino-2
      naphthol in the medium. During the continuous treatment with UASB reactors, AO7
      loading rates of 1.7 mM d(-1) (590 mg l(-1)d(-1)) were achieved, with 92% AO7
      removal efficiencies, operating with an influent comprised of AO7 (0.58 mM) and
      glucose (2 gl(-1)). In addition, when the cosubstrate was limiting (AO7 0.3 mM
      and glucose 0.25 gl(-1)), AO7 removal was significantly lower (78%).

PMID- 15743622
TI  - Effect of pH on MnOx/GAC catalyzed ozonation for degradation of nitrobenzene.
AB  - The effect of pH on MnO(x)/GAC heterogeneous catalytic ozonation was
      investigated. Nitrobenzene was used as a model refractory organic pollutant. It
      was found that in MnO(x)/GAC catalytic ozonation, the degradation efficiency of
      nitrobenzene was higher under low pH conditions (pH 2.74-3.52) than that under
      high pH conditions (pH 6.72-9.61). This result was different from the case of
      ozonation alone, in which higher pH had positive effect on the degradation of
      nitrobenzene due to the formation of hydroxyl radical. In the presence of
      MnO(x)/GAC catalyst, ozone decomposition was accelerated, and higher pH condition
      favored ozone decomposition. It was assumed that hydroxyl radicals might not be
      the dominating active species in the catalytic oxidation, for the presence of t
      butanol did not have any influence on MnO(x)/GAC heterogeneous catalytic
      ozonation. Adsorption of organic micropollutants on MnO(x)/GAC catalyst was an
      important step and would have direct influence on the effectiveness of catalytic
      oxidation. It was assumed that the organic pollutants might be further decomposed
      on the surface of catalyst.

PMID- 15743623
TI  - Fog drip and its relation to groundwater in the tropical seasonal rain forest of
      Xishuangbanna, Southwest China: a preliminary study.
AB  - Rain, fog drip, shallow soil water and groundwater were collected for two years
      (2002-2003) for stable isotopic analysis, at a tropical seasonal rain forest site
      in Xshuangbanna, Southwest China. The fog drip water ranged from -30 to +27 per
      thousand in deltaD and -6.2 to +1.9 per thousand in delta(18)O, conforms to the
      equation deltaD=7.64delta(18)O+14.32, and was thought to contain water that has
      been evaporated and recycled terrestrial meteoric water. The rain was
      isotopically more depleted, and ranged from -94 to -45 per thousand in deltaD,
      and -13.2 to -6.8 per thousand in delta(18)O. The shallow soil water had a
      composition usually between those of the rain and fog drip, and was assumed to be
      a mixture of the two waters. However, the soil water collected in dry season
      appeared to contain more fog drip water than that collected in rainy season. The
      groundwater in both seasons had an isotopic composition similar to rainwater,
      suggesting that fog drip water does not play a significant role as a source of
      recharge for the groundwater. This groundwater was thought to be recharged solely
      by rainwater.

PMID- 15743624
TI  - Wet peroxide oxidation of chlorophenols.
AB  - This study evaluates the application of Wet Peroxide Oxidation (WPO) for the
      treatment of solutions containing 4-chlorophenol (4-CP) and 2,4-dichlorophenol
      (2,4-DCP). These compounds are of special interest due to their high toxicity and
      low biodegradability. WPO is included in the Advanced Oxidation Processes, which
      are technologies based on an initial formation of hydroxyl radicals that further
      oxidize the organic matter. The influence of some operating conditions such as
      temperature, dosage of hydrogen peroxide and initial concentration of the
      chlorophenols was studied in absence of a catalyst. The results of this study
      prove that 4-CP and 2,4-DCP can be completely removed from wastewaters by means
      of WPO. Total Organic Carbon (TOC) and 4-CP removals of 72.3% and 100%,
      respectively, were achieved working at 100 degrees C with 2.5 mL of H(2)O(2) and
      an initial concentration of 500 ppm of 4-CP after 90 min of reaction. Under the
      same conditions but with an initial concentration of 500 ppm of 2,4-DCP a TOC
      removal of 59% and a complete removal of the target compound were achieved.

PMID- 15743625
TI  - Influence of operational conditions on the performance of a mesh filter activated
      sludge process.
AB  - Recently, a new type of wastewater treatment system became the focus of
      scientific research, the mesh filter activated sludge system. It is a
      modification of the membrane bioreactor where a membrane filtration process
      serves to separate the sludge from the purified effluent. The difference is that
      a mesh filter is used instead of the membrane. Due to the much larger pore size
      of the mesh, the effluent is not of the same excellent quality as with membrane
      bioreactors. Nevertheless, it still resembles the quality of the now most widely
      used standard treatment system, where settling tanks are used to retain the
      activated sludge. At the same time, the new system features all the other
      advantages of membrane bioreactors including elevated sludge concentrations
      resulting in decreased volumina of basins and complete substitution of the
      settling tank. Therefore, this process presents a potential future alternative
      where a small footprint of the plant is required. However, so far only a few
      preliminary studies on this innovative process type have been done. In this
      paper, the effects of suspended solids concentration, flux rate as well as
      aeration rate on the effluent quality are discussed. Furthermore, the
      characteristic of the sludge floc was identified as a factor of vital importance.
      Therefore, another influencing parameter, the food to microorganism (F/M) ratio,
      which is known to have a significant effect on floc characteristics, was studied.
      The main result demonstrated that the process was very effective under most of
      the operation conditions. The suspended solids concentration in the effluent was
      below 12 mg l(-1), the average COD in the effluent was between 24 and 45 mg l(-1)
      and the BOD(5) was lower than 5 mg l(-1). High flux rates of up to 150 l m(-2)h(
      1) were also achieved.

PMID- 15743626
TI  - Influence of natural organic matter on the morphology of corroding lead surfaces
      and behavior of lead-containing particles.
AB  - Influence of natural organic matter (NOM) on the morphology of lead surfaces
      exposed to drinking water and on the properties of lead-containing colloidal
      particles was explored based on the data of scanning electron microscopy,
      sequential filtrations, measurements of particle size distributions and
      electrophoretic potential. It was demonstrated that NOM prevented the formation
      of cerussite and hindered the growth of hydrocerussite crystals. Measurements of
      zeta-potential showed that the surface activity was highest for unaltered NOM,
      while ozonation and chlorination decreased it. The concentrations of soluble lead
      and tin increased several fold in the presence of NOM, while large colloidal
      particles of lead and solder corrosion products tended to break down to form
      smaller fragments. It is suggested that these phenomena are important for
      understanding of lead release mechanisms in drinking water.

PMID- 15743627
TI  - Heavy metal removal by clinoptilolite. An equilibrium study in multi-component
      systems.
AB  - Ternary and quaternary ion-exchange equilibria have been studied between heavy
      metal solution (Pb(2+), Cd(2+), Cu(2+)) and Na-form of clinoptilolite. The value
      of the ion-exchange equilibrium constant was estimated using the Langmuir,
      Competitive Langmuir, and thermodynamic sorption models. For each isotherm,
      calculations were done taking into account the concentration of ions in both
      phases. Additionally, for the thermodynamic isotherm, two other cases were
      considered: activity of ions in the liquid phase and concentration in the solid
      phase; activity of ions in both phases. The activity coefficients of ions in the
      liquid phase were determined using Pitzer's model; activity coefficients in the
      solid phase were estimated by Wilson's model. It was found that the exchange
      capacity for a given M(2+) is not constant and differs in one- or multi-component
      systems. The results show that the equilibrium model based on the law of mass
      action, which considers nonideal behavior of both phases, allows one to achieve
      the best approach to the real multi-component equilibrium data in all studied
      systems.

PMID- 15743628
TI  - Steady-state humic-acid-containing blanket in upflow suspended bed.
AB  - We investigated the effects of turbidity and concentration of humic acid on the
      steady-state behavior of the blanket, which was coagulated using polyaluminum
      chloride (PACl) as coagulant. The three-dimensional solid-flux plot was
      constructed. Based on fixed PACl dosage, the iso-humic-acid solid-flux surfaces
      stacked that enveloped the feasible regime for the blanket bed. The steady-state
      point moved toward low solid flux and low solid fraction regime with decreasing
      initial raw water turbidity and/or increasing humic-acid concentration. Low water
      turbidity and high humic-acid concentration yielded a bulky blanket, with the
      former producing clean, and the latter turbid effluent. The presence of humic
      acid was thereby harmful to blanket strength, except for the case of low raw
      water turbidity. An optimal range of humic acid for blanket strength and
      clarification efficiency existed at 1 mg l(-1). Low level of humic acid is
      beneficial to blanket development with low-turbidity raw water.

PMID- 15743629
TI  - Kinetic modeling of the radiolytic degradation of Acid Orange 7 in aqueous
      solutions.
AB  - The degradation of Acid Orange 7 (AO7) in aqueous solutions induced by gamma-ray
      irradiation was investigated in terms of both the disappearance of parent
      molecule (decoloration) and the degree of mineralization. The disappearance of
      AO7 followed pseudo first-order kinetics, whereas its mineralization could be
      described by zero-order kinetics. The pseudo first-order degradation rate
      constants were found to be proportional to irradiation dose rates and the
      reciprocals of initial AO7 concentrations. Based on the experimental results and
      a reaction analysis on the steady-state radiolysis of aerated aqueous solutions,
      a kinetic model was developed for describing the radiolytic degradation of AO7.
      Moreover, with this kinetic model, the reaction rate constants of e(aq)(-) and H.
      with AO7 were estimated as 3.0 x 10(9) and 8.4 x 10(9) x L mol(-1) s(-1),
      respectively. Taking the relative contributions of oxidative and reductive
      species to AO7 degradation into account, oxidative radiolysis proved to be a
      better approach for the degradation of AO7.

PMID- 15743630
TI  - Cross-flow microfiltration with periodical back-washing for photocatalytic
      degradation of pharmaceutical and diagnostic residues-evaluation of the long-term
      stability of the photocatalytic activity of TiO2.
AB  - The combination of semiconductor photocatalysis with cross-flow microfiltration
      accompanied by periodical back-washing was investigated in a pilot plant. The
      investigation included the testing of membrane materials because the membrane
      must resist the abrasion and the periodical back-washing. Another objective of
      this investigation was to assess the potential of two different TiO(2) materials
      (Hombikat UV100 and P25) for continuous photocatalytic degradation of persistent
      organic pollutants. The study focused on the long-term stability of the
      photocatalytic activity of TiO(2) during its continuous application. The
      combination of photocatalysis and cross-flow microfiltration allowed the
      separation and reuse of TiO(2) after the photocatalytic degradation of clofibric
      acid, carbamazepine and iomeprol. The investigations showed that the
      photocatalytic activity of P25 and Hombikat UV100 was constant during continuous
      usage over several days. This study indicates the high potential of the
      combination of heterogeneous photocatalytic oxidation processes with cross-flow
      microfiltration accompanied by periodical back-washing of the membrane. Thus
      environmentally relevant pharmaceuticals and X-ray contrast media can be
      transformed and mineralized in a continuous water treatment process.

PMID- 15743631
TI  - The effect of boiling water on disinfection by-product exposure.
AB  - Chloraminated and chlorinated waters containing bromide were used to determine
      the impact of boiling on disinfection by-product (DBP) concentrations. No
      significant changes were detected in the concentrations of the dihalogenated
      haloacetic acids (DXAAs) (i.e., dichloro-, bromochloro-, dibromoacetic acid) upon
      boiling of chloraminated water, whereas the levels of the trihalogenated
      haloacetic acids (TXAAs) (i.e., trichloro- (TCAA), bromodichloro- (BDCAA),
      dibromochloroacetic acid (DBCAA)) decreased over time (e.g., 9-37% for TCAA).
      Increased DXAA concentrations (58-68%) were detected in the boiled chlorinated
      sample, which likely resulted from residual chlorine reacting with DXAA
      precursors. TCAA concentration was unchanged after boiling chlorinated water for
      1 min, but a 30% reduction was observed after 5 min of boiling. BDCAA
      concentrations decreased 57% upon boiling for 1 min and were completely removed
      after 2 min of boiling, whereas DBCAA was removed after boiling chlorinated water
      for 1 min. Trihalomethane concentrations were reduced in both chloraminated (74
      98%) and chlorinated (64-98%) water upon boiling. Boiling chloraminated water for
      1 min reduced chloroform concentration by 75%. Chloroform was reduced by only 34%
      in chlorinated water after a 1 min boil, which indicates that simultaneous
      formation and volatilization of chloroform was occurring. Most of the remaining
      DBPs (e.g. haloketones, chloral hydrate, haloacetonitriles) were removed by at
      least 90% after 1 min of boiling in both samples. These data suggest that other
      mechanisms (e.g., hydrolysis) may have been responsible for removal of the non
      volatile DBPs and further highlight the importance of examining individual
      species when estimating thermal effects on DBP concentrations.

PMID- 15743632
TI  - Hydroxyl free radical reactivity toward aqueous chlorinated phenols.
AB  - Second-order kinetic constants (k(OH,S)) for the hydroxyl free radical attack on
      a series of nine chlorophenols (2-chlorophenol, 2,4-dichlorophenol, 2,5
      dichlorophenol, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, 2,3,5,6
      tetrachlorophenol, 2,3,4,5-tetrachlorophenol, 2,3,4,6-tetrachlorophenol, and
      pentachlorophenol) in aqueous solution were determined by means of the
      competitive kinetics method. Experimental values ranged from 3.5 x 10(09)M(-1)s(
      1) for pentachlorophenol to 8.2 x 10(09)M(-1)s(-1) for 2-chlorophenol. A general
      trend of lower kinetic constant values with higher degree of chlorination was
      observed and tested with four different correlations using Hammett's sigma
      values, the number of chlorine substituents on the aromatic ring, and estimated
      diffusion coefficients. These correlations were statistically significant
      (alpha=0.01), although the regression coefficients were moderate (R(2)<0.6).
      Statistical analysis indicated that all correlations were equally valid. This
      report includes second-order kinetic constants not previously reported for six
      chlorophenols, and also provides the means to estimate constants for other
      chlorophenols for which no experimental data are available.

PMID- 15743633
TI  - Degradation of nonylphenolic surfactants in activated sludge batch tests.
AB  - The fate of nonylphenol polyethoxylate surfactants in the activated sludge
      wastewater treatment process is a concern due to the formation of estrogenic
      nonlyphenols on degradation and due to the large amounts discharged to the
      aquatic environment through sewage treatment works. Batch tests using activated
      sludge from a Husmann apparatus were used to determine the effects of these
      compounds physico-chemical properties and biological sludge characteristics on
      biodegradation. Degradation of nonylphenol polyethoxylates with up to 12 ethoxy
      groups was observed in unacclimated sludge with a concomitant production of
      nonylphenol and short chain nonylphenol polyethoxylate compounds. Degradation was
      determined to be a biotic process involving intracellular enzyme activity, which
      resulted in sludge age being an influential parameter. With increasing sludge age
      there is an increase in mixed liquor solids concentration in activated sludge
      which results in greater bacterial numbers and the potential for greater species
      diversity which therefore increases compound degradation. However, increased
      degradation of long chain compounds resulted in an accumulation of shorter chain
      compounds and nonylphenol, which are more resistant to degradation.

PMID- 15743634
TI  - Solar and photocatalytic disinfection of protozoan, fungal and bacterial microbes
      in drinking water.
AB  - The ability of solar disinfection (SODIS) and solar photocatalytic (TiO(2))
      disinfection (SPC-DIS) batch-process reactors to inactivate waterborne protozoan,
      fungal and bacterial microbes was evaluated. After 8 h simulated solar exposure
      (870 W/m(2) in the 300 nm-10 microm range, 200 W/m(2) in the 300-400 nm UV
      range), both SPC-DIS and SODIS achieved at least a 4 log unit reduction in
      viability against protozoa (the trophozoite stage of Acanthamoeba polyphaga),
      fungi (Candida albicans, Fusarium solani) and bacteria (Pseudomonas aeruginosa,
      Escherichia coli). A reduction of only 1.7 log units was recorded for spores of
      Bacillus subtilis. Both SODIS and SPC-DIS were ineffective against the cyst stage
      of A. polyphaga.

PMID- 15743635
TI  - Chemical reduction of nitrate by nanosized iron: kinetics and pathways.
AB  - This study was conducted to investigate chemical reduction of nitrate by
      nanoscale zero-valent iron (ZVI) in aqueous solution and related kinetics and
      pathways. In the last decade, employment of micro-scale ZVI has gained its
      popularity in nitrate reduction. To further study chemical reduction of nitrate,
      nanosized iron was synthesized and tested in this work. It has a size in the
      range of 50-80 nm and a BET surface area of 37.83 m(2)g(-1). Chemical reduction
      of nitrate by nanosized iron under various pHs was carried out in batch
      experiments. Experimental results suggest that nitrate reduction by nanosized ZVI
      primarily is an acid-driven surface-mediated process. A stronger acidic condition
      is more favorable for nitrate reduction. Results of the kinetics study have
      indicated that a higher initial concentration of nitrate would yield a greater
      reaction rate constant. Additional test results also showed that the reduction
      rate of nitrate increased as the dose of nanosized ZVI increased. In all tests,
      reaction rate equations developed do not obey the first- or pseudo-first-order
      reaction kinetics with respect to the nitrate concentration. Based on the
      research findings obtained, two possible reaction pathways for nitrate reduction
      by nanoscale iron particles have been proposed in this work.

PMID- 15743636
TI  - Removal of fluoride from semiconductor wastewater by electrocoagulation
      flotation.
AB  - This work employs an anodic surfactant, sodium dodecyl sulfate (SDS), to improve
      the flotation performance of the electrocoagulation-flotation (ECF) process to
      treated fluoride containing semiconductor wastewater following calcium
      precipitation. The dissolved fluoride ions and CaF(2) particles in the wastewater
      after calcium precipitation were effectively removed in the ECF process
      simultaneously. The dosage of SDS required for ECF was much less than those for
      dispersed air flotation (DiAF) or dissolved air flotation (DAF) processes because
      the CaF(2) particles can be collected by hydro-fluoro-aluminum flocs in ECF.
      Thus, SDS only served as a frother to make the bubbles tiny and stable in the ECF
      defluoridation process. The interference of co-existing anions can be overcome by
      increasing the dosage of calcium ions and SDS. The optimum initial acidity for
      ECF is close to the initial fluoride concentration after calcium precipitation;
      the amount of SS removed dropped rapidly if the initial acidity exceeded the
      optimal value because the surface charge of the hydro-fluoro-aluminum particles
      increased. The initial acidity of the wastewater after calcium precipitation can
      be modified by changing the [Ca(OH)(2)]/[Ca(2+)](T) ratio and the appropriate
      ratio is approximately given by the acid dissociation constant of hydrofluoric
      acid and the initial pH of the wastewater before calcium precipitation.

PMID- 15743637
TI  - Advanced sewage treatment process with excess sludge reduction and phosphorus
      recovery.
AB  - An advanced sewage treatment process has been developed, in which excess sludge
      reduction by ozonation and phosphorus recovery by crystallization process are
      incorporated to a conventional anaerobic/oxic (A/O) phosphorus removal process.
      The mathematical model was developed to describe the mass balance principal at a
      steady state of this process. Sludge ozonation experiments were carried out to
      investigate solubilization characteristics of sludge and change in microbial
      activity by using sludge cultured with feed of synthetic sewage under A/O
      process. Phosphorus was solubilized by ozonation as well as organics, and acid
      hydrolyzable phosphorus (AHP) was the most part of solubilized phosphorus for
      phosphorus accumulating organisms (PAOs) containing sludge. At solubilization of
      30%, around 70% of sludge was inactivated by ozonation. The results based on
      these studies indicated that the proposed process configuration has potential to
      reduce the excess sludge production as well as to recover phosphorus in usable
      forms. The system performance results show that this system is practical, in
      which 30% of solubilization degree was achieved by ozonation. In this study, 30%
      of solubilization was achieved at 30 mgO(3)/gSS of ozone consumption.

PMID- 15743638
TI  - Quantitative and qualitative evaluation of phytoplankton communities by
      trichromatic chlorophyll fluorescence excitation with special focus on
      cyanobacteria.
AB  - We present results that were obtained with a newly developed fluorometer, the
      'PhytoSensor'. They are based on multi-wavelength excitation of chlorophyll
      fluorescence to detect the phytoplankton biomass and to identify main taxons
      (among cyanobacteria, green and brown microalgae). A method to evaluate the
      photosynthetic potential of the phytoplankton was established. Attention was
      focused on the measurement of the cyanobacterial biomass. A modelling to
      distinguish between the two spectral groups (blue and red) of cyanobacteria as a
      function of their pigments and physiological status is proposed. The main
      innovation of the device results in the recording of the fluorescence induction
      kinetics of the phytoplankton to confirm and refine the evaluation of the
      taxonomic composition. The PhytoSensor abilities were compared with pigment
      analysis, commercial fluorometers, particle and microscopic counting and
      identification. The PhytoSensor has been used with success to monitor the
      dynamics of phytoplankton in drinking-water supply reservoirs in Southeast Asia.

PMID- 15743639
TI  - Effect of OH and silanol groups in the removal of dyes from aqueous solution
      using diatomite.
AB  - The removal of methylene blue, reactive black (C-NN), and reactive yellow (MI
      2RN) from aqueous solution by calcined and raw diatomite at 980 degrees C was
      studied. These studies demonstrated the importance of the various functional
      groups on the mechanism of adsorption. The role of pore size distribution in the
      dye adsorption studies was also investigated. The adsorption isotherms were pH
      dependent. Henry and Freundlich adsorption isotherms were used to model the
      adsorption behavior and experimental results for all dyes used exhibited
      heterogeneous surface binding. The removal of the ionisable functional groups
      increased the pH(ZPC) value from 5.4 to 7.7, while FTIR, SEM and XRD analysis
      showed a remarkable decrease of the characteristic Si-OH peaks after calcinations
      at 980 degrees C. The removal of hydroxyl groups from the surface of diatomite
      lead to a decrease in the adsorption. It was evident from pH and infrared spectra
      results that mechanisms of methylene blue and reactive yellow adsorption differed
      from that of reactive black. Accordingly, adsorption on the external surface by n
      pi interaction between the pi system of the RB and the electron lone pairs of the
      oxygen atoms of siloxane group and columbic attraction between the dye and the
      surface of calcined diatomite was proposed as a possible adsorption mechanism.

PMID- 15743640
TI  - Sorption of phenols onto sandy aquifer material: the effect of dissolved organic
      matter (DOM).
AB  - The influence of dissolved organic matter (DOM) on the sorption of four phenols,
      2,4,6-trichlorophenol (2,4,6-TCP), pentachlorophenol (PCP), 2,4-dinitrophenol
      (2,4-DNP) and 2-methyl-4,6-dinitrophenol (2-M-4,6-DNP), onto sandy aquifer
      material at different pH values was investigated using flow through column
      experiments. The pH-dependent sorption of the chlorinated phenols 2,4,6-TCP and
      PCP was not significantly affected by DOM (measured as dissolved organic carbon,
      DOC), whereas in the case of nitrophenols a significant lower retardation was
      found, depending on the DOC concentration and pH value of the aqueous solution.
      Sorption decreases with increasing DOC concentration, which indicates a binding
      of these compounds by DOM. The degree of sorption reduction depends on the pH
      value and increases with increasing fraction of neutral species. The different
      behaviour of nitrophenols in comparison to the chlorophenols is assumed to be a
      result of specific charge-transfer interactions. A combined sorption and complex
      formation model was used to describe the effect of pH and DOC concentration on
      the sorption of nitrophenols onto aquifer material and to estimate binding
      coefficients of neutral nitrophenols on DOM.

PMID- 15743641
TI  - Electricity generation from cysteine in a microbial fuel cell.
AB  - In a microbial fuel cell (MFC), power can be generated from the oxidation of
      organic matter by bacteria at the anode, with reduction of oxygen at the cathode.
      Proton exchange membranes used in MFCs are permeable to oxygen, resulting in the
      diffusion of oxygen into the anode chamber. This could either lower power
      generation by obligate anaerobes or result in the loss in electron donor from
      aerobic respiration by facultative or other aerobic bacteria. In order to
      maintain anaerobic conditions in conventional anaerobic laboratory cultures,
      chemical oxygen scavengers such as cysteine are commonly used. It is shown here
      that cysteine can serve as a substrate for electricity generation by bacteria in
      a MFC. A two-chamber MFC containing a proton exchange membrane was inoculated
      with an anaerobic marine sediment. Over a period of a few weeks, electricity
      generation gradually increased to a maximum power density of 19 mW/m(2) (700 or
      1000 Omega resistor; 385 mg/L of cysteine). Power output increased to 39 mW/m(2)
      when cysteine concentrations were increased up to 770 mg/L (493 Omega resistor).
      The use of a more active cathode with Pt- or Pt-Ru, increased the maximum power
      from 19 to 33 mW/m(2) demonstrating that cathode efficiency limited power
      generation. Power was always immediately generated upon addition of fresh medium,
      but initial power levels consistently increased by ca. 30% during the first 24 h.
      Electron recovery as electricity was 14% based on complete cysteine oxidation,
      with an additional 14% (28% total) potentially lost to oxygen diffusion through
      the proton exchange membrane. 16S rRNA-based analysis of the biofilm on the anode
      of the MFC indicated that the predominant organisms were Shewanella spp. closely
      related to Shewanella affinis (37% of 16S rRNA gene sequences recovered in clone
      libraries).

PMID- 15743642
TI  - Does 'welfare-to-work' work? A systematic review of the effectiveness of the UK's
      welfare-to-work programmes for people with a disability or chronic illness.
AB  - Welfare-to-work programmes promoting employment of people with a disability or
      chronic illness are an expanding aspect of welfare reform in the UK. What
      evidence is there of impact on employment outcomes? This paper presents a
      systematic review of the evidence on UK policy initiatives. Both quantitative and
      qualitative studies were identified: 5399 abstracts were located, from which 16
      studies were critically appraised. Overall, each of the five main welfare-to-work
      strategies operating in the 1990s helped people with disabilities into work, who
      were previously on benefits. The proportion of participants gaining employment
      after involvement ranged from 11% to 50%, dependent on characteristics of
      participants, such as 'job-readiness', as well as wider labour market context. As
      most studies were uncontrolled, it was difficult to determine if the improved
      employment chances were due to the effectiveness of the welfare-to-work
      interventions themselves or to external factors. Wider impact, such as uptake of
      schemes as a proportion of the total target population, was weak. The qualitative
      components identified barriers and facilitators concerned with effective
      implementation, to aid design of future initiatives.

PMID- 15743643
TI  - The impact of media coverage of the suicide of a well-known Quebec reporter: the
      case of Gaetan Girouard.
AB  - Evidence of a media impact on suicide is mixed and needs further research. The
      main objective of this article is to document the effects of the media coverage
      following the suicide of a well-known and popular television reporter in Quebec,
      Canada. A content analysis of the printed media and an analysis of suicide rates
      during the following year, of coroners' records and of calls to Suicide
      Prevention Centres during the following 3 months was conducted. Most guidelines
      for responsible reporting of a suicide were not applied. The results showed a
      rise in the suicides rates immediately after the reporter's suicide, especially
      by hanging as in the original case. A cluster of six suicides by hanging also
      took place in the small municipality where the reporter's suicide occurred. There
      was also an indication of direct influence in the coroners' records and a rise in
      calls to Suicide Prevention Centres. This research indicates that the reporting
      of the suicide of a popular figure preceded an important rise in the number of
      suicides. A possible theoretical explanation is that a positive role model
      appeared to suddenly fail to cope with life, thus creating high distress and
      cognitive dissonance in the audience. The news media should apply more caution
      and follow recommended guidelines in reporting this type of news.

PMID- 15743644
TI  - Beyond blame: cultural barriers to medical incident reporting.
AB  - The paper explores the attitudes of medical physicians towards adverse incident
      reporting in health care, with particular focus on the inhibiting factors or
      barriers to participation. It is recognised that there are major barriers to
      medical reporting, such as the 'culture of blame'. There are, however, few
      detailed qualitative accounts of medical culture as it relates to incident
      reporting. Drawing on a 2-year qualitative case study in the UK, this paper
      presents data gathered from 28 semi-structured interviews with specialist
      physicians. The findings suggest that blame certainly inhibits medical reporting,
      but other cultural issues were also significant. It was commonly accepted by
      doctors that errors are an 'inevitable' and potentially unmanageable feature of
      medical work and incident reporting was therefore 'pointless'. It was also found
      that reporting was discouraged by an anti-bureaucratic sentiment and rejection of
      excessive administrative duties. Doctors were also apprehensive about the
      increased potential for managers and non-physicians to engage in the regulation
      of medical quality through the use of incident data. The paper argues that the
      promotion of incident reporting must engage with more than the ubiquitous
      'culture of blame' and instead address the 'culture of medicine', especially as
      it relates to the collegial and professional control of quality.

PMID- 15743645
TI  - How acceptable are innovative health-care technologies? A survey of public
      beliefs and attitudes in England and Wales.
AB  - There has been a continuing debate about the extent to which the public finds
      health-care technological innovation acceptable. The public's ambivalence about
      scientific medicine may have been exacerbated, more recently, by developments
      such as the introduction of the 'new genetics' with their associated ethical and
      social implications and the claims that public trust in health care and
      practitioners and, more widely, in society has been eroded. The aim of this paper
      is to examine public attitudes to a range of innovative health-care technologies
      to see whether (i) certain technologies are perceived as particularly
      problematic, and (ii) attitudes to new health-care technologies are associated
      more broadly with beliefs about science, trust in health care and social trust,
      and perceptions of the benefits and risks of complementary and alternative
      medicine versus orthodox (technological) medicine. These questions are examined
      through a statistical analysis of data collected in a national, postal survey of
      the adult population (n = 1187) in England and Wales. The results showed public
      ambivalence about new health-care technologies, although genetic technologies, as
      a whole, were not seen to be problematic and their acceptability depended on
      their ability to control serious diseases. However, there was a level of
      consistency in attitude across the different technologies. Those consistently
      against new health-care technologies were also more likely to be suspicious of
      science, and doubtful about the benefits of other established, orthodox
      technologies (screening; medications) and to have less trust in health and health
      care practitioners.

PMID- 15743646
TI  - Doing criticism in 'symbiotic niceness': a study of palliative care nurses' talk.
AB  - This paper examines how palliative care nurses do criticism of other
      professionals in talk within settings for care of the dying (two hospices and one
      general hospital). Strategies for the production of moral identities include the
      use of direct criticism, indirect criticism and quoted speech, hence 'inverted
      comma criticism'. Criticism is done through the construction and reconstruction
      of 'atrocity stories'. Atrocity stories are used as a medium by nurses to express
      their opinions and feelings about doctors who might have behaved insensitively.
      At the same time, it allows doctors to redeem themselves. The analysis of talk
      reveals that the voices of absent patients are reactivated and co-opted into the
      nurses' talk. The stories serve to produce an image of nurses as caring, morally
      responsible patient advocates and loyal characters to their medical colleagues.
      Through the analysis of talk, the communication skills and strategies for the
      maintenance of interactional order are made visible and displayed. Skills for the
      production of the palliative care team work are also made visible. Emotional
      labour is analysed as a project for the production of particular kinds of
      niceness which in turn require particular types of emotional labour. This paper
      argues that educators should aim to identify and make conscious use of nurses'
      own available interactional skills, and focus on valuable cultural (rules of
      decorum) and material resources (the disease process) which are readily available
      and accessible for nurses, as a starting point in communication training. The
      theory of an account of co-production of niceness which benefits each other,
      hence, symbiotic niceness, reveals that being nice to each other can be rewarding
      and therapeutic in that it helps to smooth, distance and ameliorate problems
      occurring in the reality of palliative care nurses' and their patients' life
      worlds.

PMID- 15743647
TI  - Physicians' attitudes towards end-of-life decisions: a comparison between seven
      countries.
AB  - In the context of an European collaborative research project (EURELD), a study on
      attitudes towards medical end-of-life decisions was conducted among physicians in
      Belgium, Denmark, Italy, the Netherlands, Sweden and Switzerland. Australia also
      joined the consortium. A written questionnaire with structured questions was sent
      to practising physicians from specialties frequently involved in the care of
      dying patients. 10,139 questionnaires were studied. Response rate was equal to or
      larger than 50% in all countries except Italy (39%). Apart from general agreement
      with respect to the alleviation of pain and symptoms with possible life
      shortening effect, there was large variation in support--between and within
      countries--for medical decision that may result in the hastening of death. A
      principal component factor analysis found that 58% of the variance of the
      responses is explained by four factors. 'Country' explained the largest part of
      the variation of the standardized factor scores.

PMID- 15743648
TI  - Diversity in clinical guidelines: the role of repertoires of evaluation.
AB  - Clinical practice guidelines are one of the main tools by which clinicians,
      policy makers and patients hope to make health care less variable, more reliable
      and efficient, but there is little understanding of the processes by which
      clinical guidance is put together by guideline groups. This paper describes the
      social organisation of knowledge within clinical practice guideline development
      processes by drawing on the sociology of situated judgement. Two guideline
      development processes were observed, and the development group meetings (N = 21)
      recorded and analysed qualitatively. Data analysis suggested that clinical
      guidance comes to existence through the combination of repertoires of evaluation,
      organised around four different epistemic criteria: robustness, usability,
      acceptability and adequacy. This research provides a detailed and layered
      understanding of the knowledge dynamics involved in developing recommendations
      for appropriate health care for specific clinical circumstance.

PMID- 15743649
TI  - Socioeconomic status and weight change in adults: a review.
AB  - In developed countries, obesity is inversely associated with socioeconomic status
      (SES) among women, and less consistently among men; whereas, in developing
      countries, the association is direct. However, the relationship of SES to weight
      change over time is unknown. This relationship was the focus of the present
      literature review. It was hypothesized that, compared with persons of higher SES,
      persons of low SES would show greater weight gain or risk of weight gain over
      time. A search of electronic databases identified 34 relevant articles from
      developed countries reporting on studies that assessed the relationship of
      various measures of SES with weight change over time in adults (there were too
      few papers from developing countries (n = 1) to include). Results of the
      methodologically strongest studies (those which obtained objectively measured
      adiposity data and used a follow-up period of 4 years or more) showed that, among
      non-black samples, there were relatively consistent inverse associations between
      occupation and weight gain for men and women. When SES was assessed using
      education, evidence was slightly less consistent, but still provided some support
      for the hypothesized relationship. However, when income was used as the indicator
      of SES, findings were inconsistent, although there were fewer studies available.
      There was little support for a relationship between SES and weight gain for black
      samples. In the context of the worldwide epidemic of obesity, these findings
      suggest that in developed countries, weight gain prevention efforts might best be
      focused on those who are most socioeconomically disadvantaged, particularly those
      in lower status occupations.

PMID- 15743650
TI  - Low levels of maternal education and the proximate determinants of childhood
      mortality: a little learning is not a dangerous thing.
AB  - This paper examines the impact of 'low' levels of maternal education on the
      proximate determinants of child mortality using data from the 1992/93 Indian
      National Family Health Survey. Twenty-two outcomes are investigated, representing
      child mortality and morbidity, illness management, service utilization and health
      behaviours. Maternal education is a significant correlate of each of the
      outcomes, and even low levels of education increase child survival prospects and
      health-related behaviours, except for neonatal mortality and the effective
      management of diarrhoea. We speculate on some of the possible mechanisms behind
      such impressive findings and suggest that rather than female autonomy, it may be
      the 'hidden curriculum' values of discipline and obedience of authority that
      account for them.

PMID- 15743651
TI  - Prehospital delay and independent/interdependent construal of self among Japanese
      patients with acute myocardial infarction.
AB  - Reducing the time from symptom onset to reperfusion therapy is an important
      approach to minimizing myocardial damage and to preventing death from acute
      myocardial infarction (AMI). Previous studies suggest that certain ethnic or
      national groups, such as the Japanese, are more likely to delay in accessing care
      than other groups. The aims of this paper were the following; (1) to examine
      whether culture (defined as independent and interdependent construal of self) is
      associated with delay in accessing medical care in Japanese patients experiencing
      symptoms of AMI; (2) to determine if the relationship between independent and
      interdependent construal of self and prehospital delay time is mediated by
      cognitive responses and/or emotional responses; and (3) to determine if
      independent and interdependent construal of self independently predicts choice of
      treatment site (clinic vs. hospital). A cross-sectional study was conducted at
      hospitals in urban areas in Japan. One hundred and forty-five consecutive
      patients who were admitted with AMI within 72 h of the onset of symptoms were
      interviewed using the modified response to symptoms questionnaire and the
      independent and interdependent construal of self scale. The interdependent
      construal of self scores were significantly associated with prehospital delay
      time, controlling for demographics, medical history, and symptoms (p<.001).
      However, the relationship between independent and interdependent self and
      prehospital delay times was not mediated by cognitive or emotional responses. In
      multiple logistic regression analysis, patients with high independent construal
      of self were more likely to seek care at a hospital rather than a clinic compared
      to those with lower independent construal of self. In conclusion, cultural
      variation within this Japanese group was observed and was associated with
      prehospital delay time.

PMID- 15743652
TI  - Breast-feeding, day-care attendance and the frequency of antibiotic treatments
      from 1.5 to 5 years: a population-based longitudinal study in Canada.
AB  - This paper aims to study, at the population level, the protective role of breast
      feeding on child health and its relation to day-care attendance during the first
      5 years of life. The analysis, done on a national sample of children, uses
      antibiotic treatments as a general measure of health. It takes into account
      mother's education level, family poverty level, mother's smoking status during
      pregnancy and after birth, mother's age, sex, gestation duration, and birth rank.
      The analyses were performed using data from the Longitudinal Study of Child
      Development in Quebec (LSCDQ), conducted by Sante Quebec, a division of the
      Institut de la Statistique du Quebec (ISQ). The study was based on face-to-face
      interviews and included a set of questionnaires addressed to the children's
      mothers and fathers. A total of 1841 were included in the sample analyzed.
      Detailed information on breast-feeding and complementary feeding was collected at
      5 and 17 months through face-to-face interviews with the most knowledgeable
      person, generally the mother. From this information, it has been possible to
      estimate breast-feeding duration and exclusivity. Our results indicate that the
      positive effects of breast-feeding on health persist up to the second year of
      life, even in the presence of day-care attendance. The analyses indicate that
      breast-feeding reduced the number of antibiotic treatments given to children
      entering day care before 2.5 years of age. The study also indicates that the more
      at-risk children could be protected by breast-feeding and by being taken care of
      in a familial setting, especially before 2.5 years of age. Mother's education,
      family poverty level, and other social inequality indicators did not play a role
      in the frequency of antibiotic treatments. Over the long term, it will be
      important to continue to monitor the health of children and to implement public
      health interventions aimed at reducing health problems among children of
      preschool age.

PMID- 15743653
TI  - The impact of socio-economic factors on functional status decline among community
      dwelling older adults in China.
AB  - The purpose of this paper is to examine the impact of baseline socio-economic
      factors on functional status decline over a period of 3 years among a sample of
      Chinese older men and women, using the China Health and Nutrition Surveys of 1997
      and 2000. In addition, the study tries to determine whether risk differentials by
      these socio-economic factors can be explained by other demographic, health
      related and nutritional risk factors. The eligible study population was defined
      as women and men aged 55 years and over who at baseline were free from any form
      of disablement in activities of daily living (ADLs) or instrumental activities of
      daily living (IADL) tasks. Among subjects with complete data at followed-up (N =
      976), the overall incidence proportions of any functional status decline, IADL
      only and ADL declines were 25.8%, 18.9% and 6.9%, respectively. Our study found
      that education is strongly and inversely associated with incidence of combined
      functional status decline and IADL only but not with the onset of ADL disability.
      Similarly, household income per capita was inversely associated with functional
      status decline and IADL disability incidence, with a clear dose-response
      relationship, even after adjustment for age and gender. However, multivariate
      analysis demonstrated that the latter association was highly confounded by other
      demographic factors, especially urban-rural area of residence. Using a combined
      measure of socio-economic status that includes years of education and household
      income per capita, the age and gender-adjusted odds ratio for functional status
      decline and belonging to lower SES class as compared to middle, upper middle and
      upper classes was 3.82 (95% CI: 2.15, 6.77) and 2.77 (95% CI: 1.52, 5.03) after
      further adjustment for urban-rural area of residence and living arrangements.
      Hence, there are wide socio-economic disparities in the functional health of
      older adults in China, although such disparities are more seen for IADL decline
      and are almost exclusively attributed to differentials in educational attainment.
      Finally, nutritional and health-related risk factors do not seem to act as
      intermediate factors in this association and hence further research should try to
      uncover other mechanisms by which SES affects changes in functional health among
      older adults in China.

PMID- 15743654
TI  - Location, location, location: contextual and compositional health effects of
      social capital in British Columbia, Canada.
AB  - After decades of epidemiological exploration into individual-level risk factors
      for ill health, a recent surge of interest in the health effects of socially
      patterned attributes of geographically defined 'places' has given the structural
      side of the agency-structure debate new prominence in population health research.
      Utilizing two original data sets, one pertaining to features of communities in
      British Columbia, Canada and the other to characteristics of individuals living
      in them, this article distinguishes the health effects of socially patterned
      attributes of communities, including the social capital of communities, from the
      health effects of characteristics of residents that contribute to social capital,
      e.g., trust and participation in voluntary associations. Results from multilevel
      analysis demonstrated that, of three different individual-level measures of
      health and well-being (and including measures of long-term limiting illness and
      self-rated health), only a measure of depressive symptoms had variability that
      could be reasonably attributed to the level of the community. The social capital
      of communities in the form of the availability of public spaces explained some of
      this variability, but in the direction contrary to expectations. Overall,
      location (community of residence) did little to explicate health inequalities in
      this context. The strongest predictors of health in multivariate and multilevel
      models were characteristics of individual survey respondents, namely, income,
      trust in politicians and governments, and trust in other members of the
      community. Breadth of participation in networks of voluntary association was not
      significantly related to health in multivariate models.

PMID- 15743655
TI  - A multilevel analysis of ethnic variation in depressive symptoms among
      adolescents in the United States.
AB  - This study examines linkages between ethnicity and symptoms of depression among
      adolescents, with a specific focus on the intersection of individual- and
      contextual-level risk factors. Data are from the National Longitudinal Study of
      Adolescent Health (Add Health), a panel survey of a nationally representative
      United States sample (analytic N = 18,473) of students in the 7th through 12th
      grades. Depressive symptoms are measured with a 16-item subscale of the Center
      for Epidemiologic Studies-Depression Scale. Hierarchical linear modeling is used
      to estimate the simultaneous effects of individual-level ethnicity, sex, age,
      family structure, and socioeconomic status (SES), and community-level ethnic
      composition and SES, operationalized by collapsing United States Census tract
      data to the school sampling area. There is significant variation in depressive
      symptoms among sampling areas and both individual- and contextual-level
      characteristics exert effects on depressive symptomatology. The impact of
      individual-level ethnicity on depressive symptoms depends upon characteristics of
      the sampling area, in that African American teens living within predominantly Non
      Hispanic White areas are at especially high risk for frequent depressive
      symptoms. The findings demonstrate that the emotional consequences of membership
      in an ethnic group are in some instances contingent upon social context.

PMID- 15743656
TI  - Framing the fetus in medical work: rituals and practices.
AB  - What does it mean to investigate the fetus, and what might be the potential
      consequences? Although a number of feminists have engaged with the debate around
      the status of the fetus in terms of the possible implications for women,
      discussion of fetuses has been avoided by many feminists, in response to the
      politics around the abortion debate. However, there has recently been a move to
      explore the ways in which the meanings and significance of the fetus can be
      socially constructed. Set within a United Kingdom context, this paper focuses on
      two areas which are arguably changing perceptions of the fetus: the recent
      'discovery' of fetal 'pain'; and the growing recognition of the fetus as a
      patient. One of the key concerns of those who support the autonomy of women is
      that any increasing discourse around the concept of fetal patienthood may promote
      the notion of fetal personhood, which in turn may affect the status of pregnant
      women. In exploring perceptions of the fetus, this article firstly cites some of
      the key policy documents and medical articles which were published during the
      1990s, looking at apparent shifts in the ways in which the fetus is discussed in
      terms of pain and patienthood. It then explores how practitioners from different
      disciplines talked about fetal pain and patienthood in relation to the clinical
      setting. Although this paper does not provide conclusive evidence of a wholesale
      shift in terms of how the fetus is perceived by practitioners, it does point to
      subtle shifts occurring, which may or may not be significant. It is important to
      track such shifts closely, primarily because of the potential impact on women,
      but also for others involved, including practitioners. Such tracking needs to be
      set within specific cultural and policy contexts.

PMID- 15743657
TI  - Translators and mediators: bilingual young people's accounts of their
      interpreting work in health care.
AB  - The interpreting work bilingual young people do in health care settings has
      largely been seen as a social problem, indicating deficiencies either in parents'
      language skills or in the provision of professional interpreting services. Little
      research has addressed this contribution young people make to health care work
      from their perspectives. This study explored the accounts of bilingual young
      people from four linguistic groups in London, including those from established
      minority groups and those more recently arrived. Young people reported extensive
      experience of interpreting in a number of settings, and identified a range of
      benefits to themselves and their families arising from their contributions, as
      well as some problems faced in achieving successful encounters. Focusing on young
      people's own accounts enabled their work to be conceptualised not as merely
      'inappropriate and inadequate interpreting' but as a varied contribution to the
      informal economy of health care that ranged from simple translation to complex
      mediation between families, the wider community and the health care system.

PMID- 15743658
TI  - Antibiomedicine belief and integrative health seeking in Taiwan.
AB  - The newly emerged concept of integrative medicine may provoke a closer
      investigation into the pattern of biomedicine use in the context of medical
      pluralism. In this study, I propose two concepts to examine the complicated
      cognitive and behavioural responses to biomedicine (Western medicine, xi-yi) in
      relation to the use of non-biomedical therapies in Taiwan, a society with
      renowned medical pluralism. Data came from a nation-wide telephone survey
      conducted during September 2002 among community-resident population aged 20 and
      older. The sample includes 1517 respondents. The first concept--antibiomedicine-
      includes three indicators to measure an individual's negative stance on xi-yi:
      overall competence, capability to cure from within, and side effects. Combined,
      these three indicators were further constructed into a single composite index:
      antibiomedicine beliefs. Integrative health seeking tackled two aspects of health
      seeking: selective use and adaptive use. The former concerns particularly the use
      of specific ingredients of biomedicine. In this study, emphasis was placed on the
      diagnosis versus treatment of xi-yi. The latter was focussed on the strategic
      uses of xi-yi in the face of its limitation and incompetence. Three types of
      adaptive health use were identified: alternative type, complementary type, and
      exclusive type. Results of the analyses indicate that antibiomedicine belief held
      explanatory potential to selective use and adaptive use of xi-yi. The study sheds
      light on further exploring the blending of health-seeking practices and "hybrid"
      medicine. It is suggested that novel explanatory constructs and more
      sophisticated study designs should be developed to articulate the sequential of
      pluralistic health-seeking process.

PMID- 15743659
TI  - "Sneaky disease": the body and health knowledge for people at risk for coronary
      heart disease in Ontario, Canada.
AB  - The contribution of modifiable risk factors to the prevalence of coronary heart
      disease (CHD) has been well documented in the literature. A focus group component
      of a cardiovascular risk reduction project, The Community Outreach in Heart
      Health and Risk Reduction Trial was designed to explore issues that facilitate or
      constrain individual efforts to implement changes to health behaviours. Eight
      focus groups were conducted in urban, northern and rural sites in Ontario,
      Canada. In this article, we elaborate on the difficulties all group members
      experienced as they attempted to interpret their personal candidacy for CHD. For
      many participants, CHD was an undetectable or "sneaky disease" in its earlier
      stages, thus coronary risk was to them an abstract concept that could not
      ordinarily be detected through sensory perception. Participants drew on three
      possible strategies to determine their candidacy for CHD: they cognitively
      engaged in weighing risks, they relied on the interpretive powers of medical
      hermeneutics, or they waited for "the big event". The findings suggest that lay
      understandings of the body and health differ from those of health professionals
      and educators, and that lay understandings differ according to SES and gender.
      This has implications for health literacy and must be considered in devising
      strategies for health education.

PMID- 15743660
TI  - Role of socialization in explaining social inequalities in health.
AB  - This paper argues that social selection, materialist/structural and
      cultural/behavioural explanations for social inequalities in health are related
      to each other through the mechanism of socialization, seen here as a process
      through which societies shape patterns of behaviour and being that then affect
      health. Socialization involves the inter- and intragenerational transfer of
      attitudes, beliefs and behaviours. Parallels between socialization theory and
      Bourdieu's concept of habitus are also drawn, and the implications for social
      epidemiology are discussed. Four key areas that would benefit from research
      within the socialization framework are identified: health behaviours,
      psychological vulnerability, social skills and future time perspective.

PMID- 15743661
TI  - Guiding the design and selection of interventions to influence the implementation
      of evidence-based practice: an experimental simulation of a complex intervention
      trial.
AB  - A consistent finding in health services research is the report of uneven uptake
      of research findings. Implementation trials have a variable record of success in
      effectively influencing clinicians' behaviour. A more systematic approach may be
      to conduct Intervention Modelling Experiments before service-level trials,
      examining intervention effects on 'interim endpoints' representing clinical
      behaviour, derived from empirically supported psychological theories. The
      objectives were to: (1) Design Intervention Modelling Experiments by backward
      engineering a 'real-world' randomised controlled trial (NEXUS); (2) examine the
      applicability of psychological theories to clinical decision-making; (3) explore
      whether psychological theories can illuminate how interventions achieve their
      effects. A 2 x 2 factorial randomised controlled trial was designed with pre- and
      post-intervention data collection by postal questionnaire surveys. The first
      survey was used to generate feedback data and the interventions were delivered in
      the second survey. General medical practitioners (GPs) in England and Scotland
      participated. First survey respondents were randomised twice to receive or not
      audit and feedback and educational reminder messages. The main outcome measures
      included behavioural intention (general plan to refer for lumbar X-rays) and
      simulated behaviour (specific, scenario-based, decisions to refer for lumbar X
      ray). Predictors were attitude, subjective norm, perceived behavioural control
      (theory of planned behaviour), self-efficacy (social cognitive theory) and
      decision difficulty. Both interventions significantly influenced simulated
      behaviour, but neither influenced behavioural intention. There were no
      interaction effects. All theoretically derived cognitions significantly predicted
      simulated behaviour. Only subjective norm was not predictive of behavioural
      intention. The effect of audit and feedback on simulated behaviour was mediated
      through perceived behavioural control. The results of this study suggest that
      Intervention Modelling Experiments, using psychological models to help isolate
      mediators of clinical decision-making, may be a means of developing more potent
      interventions, and selecting implementation interventions with a greater
      likelihood of success in a service-level randomised controlled trial.

PMID- 15743662
TI  - Health care and illegality: a survey of undocumented pregnant immigrants in
      Geneva.
AB  - Little is known about the conditions of life and the specific health problems of
      pregnant, undocumented immigrants. This study describes the socio-demographic
      characteristics and health problems encountered during pregnancy among uninsured,
      undocumented immigrants in Geneva, Switzerland. A socio-demographic questionnaire
      was completed by 134 pregnant and undocumented women (mean age 27.8 years) who
      attended a free antenatal facility between October 2002 and October 2003. The
      first control of pregnancy was at a median of 10.5 weeks (range 5-33) of
      amenorrhoea. They were mostly Latino-American (78%), had a median 12 years of
      education but almost exclusively performed domestic work (91%) after an average
      residence in Geneva of 18 months. Half of the 62 mothers had left at least one
      child in their home country. One out of three had never had a cervical smear test
      and 13% were not immune to rubella. Unintended pregnancies (83%), mostly resulted
      from lack of contraception (70%). All but one delivery were simple, with a median
      maternity inpatient stay of 5 days (range 2-10). This population of undocumented,
      pregnant immigrants comprised mostly highly educated, young, Latino-American
      women living in poor housing conditions and wages below the legal minimum. The
      study identified the high proportion of unintended pregnancies as a major health
      issue. Future research should target these issues and programs addressing lack of
      access to preventive measures. As well as this, the specific needs of this hard
      to-reach population, such as contraception advice, rubella vaccination and
      cervical cancer screening, should be supported.

PMID- 15743664
TI  - Cancer and aging at the crossroads.

PMID- 15743665
TI  - DeltaNp53 or p44: priming the p53 pump.
AB  - The human protein DeltaNp53 and its murine counterpart p44 are isoforms of the
      tumor suppressor p53 lacking the transactivation domain present in the first 39
      (40 in mouse) amino acids of the full-length protein. This makes them similar in
      structure to the DeltaN isoforms of the other members of the p53 superfamily of
      transcription factors, p63 and p73. The principle way both the human and the
      murine proteins are generated is by alternative translation of the p53 mRNA
      utilizing a start site in exon 4. Choice of start site depends on an interaction
      between p53 and its cognate RNA. When the balance between DeltaNp53 (p44) and
      full-length p53 is altered, the function of p53 as a transcription factor is
      disturbed. One consequence of over-expressing p44 in mice is an acceleration of
      the aging process and altered expression of genes in the IGF-1 signaling cascade
      [Maier, B., Gluba, W., Bernier, B., Turner, T., Mohammad, K., Guise, T., et al.
      (2004). Modulation of mammalian lifespan by the short isoform of p53. Genes &
      Development, 18, 306-319]. This links p53 to the single most important growth
      factor pathway known to regulate lifespan in lower organisms.

PMID- 15743666
TI  - Poly(ADP-ribose) polymerases: managing genome stability.
AB  - The importance of poly(ADP-ribose) metabolism in the maintenance of genomic
      integrity following genotoxic stress has long been firmly established. Poly(ADP
      ribose) polymerase-1 (PARP-1) and its catabolic counterpart, poly(ADP-ribose)
      glycohydrolase (PARG) play major roles in the modulation of cell responses to
      genotoxic stress. Recent discoveries of a number of other enzymes with poly(ADP
      ribose) polymerase activity have established poly(ADP-ribosyl)ation as a general
      biological mechanism in higher eukaryotic cells that not only promotes cellular
      recovery from genotoxic stress and eliminates severely damaged cells from the
      organism, but also ensures accurate transmission of genetic information during
      cell division. Additionally, emerging data suggest the involvement of poly(ADP
      ribosyl)ation in the regulation of intracellular trafficking, memory formation
      and other cellular functions. In this brief review on PARP and PARG enzymes,
      emphasis is placed on PARP-1, the best understood member of the PARP family and
      on the relationship of poly(ADP-ribosyl)ation to cancer and other diseases of
      aging.

PMID- 15743667
TI  - The human mitochondrial proteome: oxidative stress, protein modifications and
      oxidative phosphorylation.
AB  - Mitochondria are one of the most complex of subcellular organelles and play key
      roles in many cellular functions including energy production, fatty acid
      metabolism, pyrimidine biosynthesis, calcium homeostasis, and cell signaling. In
      recent years, we and other groups have attempted to identify the complete set of
      proteins that are localized to human mitochondria as a way to better understand
      its cellular functions and how it communicates with other cell compartment in
      complex signaling pathways such as oxidative stress and apoptosis. Indeed, there
      is an increasing interest in understanding the molecular details of oxidative
      stress and the mitochondrial role in this process, as well as assessing how
      mitochondrial proteins become damaged or posttranslationally modified as a
      consequence of a major change in a cell's redox status. In this review, we report
      on the current status of the human mitochondrial proteome with an emphasis
      towards understanding how mitochondrial proteins, especially the proteins that
      make up the respiratory chain or oxidative phosphorylation (OXPHOS) enzymes, are
      modified in various models of age-related diseases such as cancer and Parkinson's
      disease (PD).

PMID- 15743668
TI  - Stem cell: balancing aging and cancer.
AB  - Stem cells are defined by their self-renewing capacity and the ability to
      differentiate into one or more cell types. Stem cells can be divided, depending
      on their origin, into embryonic or adult. Embryonic stem cells derive from early
      stage embryos and can give rise to cells from all three germ layers. Adult stem
      cells, first identified in hematopoietic tissue, reside in a variety of adult
      tissues. Under normal physiologic conditions, adult stem cells are capable of
      differentiating into the limited cell types that comprise the particular tissue
      or organ. Adult stem cells are responsible for tissue renewal and exhaustion of
      their replicative capacity may contribute to tissue aging. Loss of unlimited
      proliferative capacity in some of the adult stem cells and/or their progenitors
      may have involved the evolutionary trade-off: senescence prevents cancer but may
      promote aging. Embryonic stem cells exhibit unlimited self-renewal capacity due
      to the expression of telomerase. Although they possess some cancer cell
      characteristics, embryonic stem cells exhibit a remarkable resistance to genomic
      instability and malignant transformation. Understanding the tumor suppressive
      mechanisms employed by embryonic stem cells may contribute to the development of
      novel cancer treatments and safe cell-based therapies for age-related diseases.

PMID- 15743669
TI  - Dopaminergic neurons.
AB  - Dopaminergic neurons of the midbrain are the main source of dopamine (DA) in the
      mammalian central nervous system. Their loss is associated with one of the most
      prominent human neurological disorders, Parkinson's disease (PD). Dopaminergic
      neurons are found in a 'harsh' region of the brain, the substantia nigra pars
      compacta, which is DA-rich and contains both redox available neuromelanin and a
      high iron content. Although their numbers are few, these dopaminergic neurons
      play an important role in the control of multiple brain functions including
      voluntary movement and a broad array of behavioral processes such as mood,
      reward, addiction, and stress. Studies into the developmental pathways which are
      involved in the generation of dopaminergic neurons in the brain have led to the
      identification of several specific transcription factors including Nurr1, Lmx1b
      and Pitx3, all shown to be important in the development of the mesencephalic
      dopaminergic system. The selective degeneration of these dopaminergic neurons in
      the substantia nigra pars compacta leads to PD but the exact cause for this
      nigral cell loss is still unknown.

PMID- 15743670
TI  - Genetic alterations in accelerated ageing syndromes. Do they play a role in
      natural ageing?
AB  - The molecular mechanisms leading to human senescence are still not known mostly
      because of the complexity of the process. Different research approaches are used
      to study ageing including studies of monogenic segmental progeroid syndromes.
      None of the known progerias represents true precocious ageing. Some of them,
      including Werner (WS), Bloom (BS), and Rothmund-Thomson syndromes (RTS) as well
      as combined xeroderma pigmentosa-Cockayne syndrome (XP-CS) are characterised by
      features resembling precocious ageing and the increased risk of malignant
      disease. Such phenotypes result from the mutations of the genes encoding proteins
      involved in the maintenance of genomic integrity, in most cases DNA helicases.
      Defective functioning of these proteins affects DNA repair, recombination,
      replication and transcription. Other segmental progeroid syndromes, such as
      Hutchinson-Gilford progeria (HGPS) and Cockayne syndrome are not associated with
      an increased risk of cancer. In this paper we present the clinical and molecular
      features of selected progeroid syndromes and describe the potential implications
      of these data for studies of ageing and cancer development.

PMID- 15743671
TI  - The signals and pathways activating cellular senescence.
AB  - Cellular senescence is a program activated by normal cells in response to various
      types of stress. These include telomere uncapping, DNA damage, oxidative stress,
      oncogene activity and others. Senescence can occur following a period of cellular
      proliferation or in a rapid manner in response to acute stress. Once cells have
      entered senescence, they cease to divide and undergo a series of dramatic
      morphologic and metabolic changes. Cellular senescence is thought to play an
      important role in tumor suppression and to contribute to organismal aging, but a
      detailed description of its physiologic occurrence in vivo is lacking. Recent
      studies have provided important insights regarding the manner by which different
      stresses and stimuli activate the signaling pathways leading to senescence. These
      studies reveal that a population of growing cells may suffer from a combination
      of different physiologic stresses acting simultaneously. The signaling pathways
      activated by these stresses are funneled to the p53 and Rb proteins, whose
      combined levels of activity determine whether cells enter senescence. Here we
      review recent advances in our understanding of the stimuli that trigger
      senescence, the molecular pathways activated by these stimuli, and the manner by
      which these signals determine the entry of a population of cells into senescence.

PMID- 15743672
TI  - Cancer and aging: the importance of telomeres in genome maintenance.
AB  - Telomeres are the specialized DNA-protein structures that cap the ends of linear
      chromosomes, thereby protecting them from degradation and fusion by cellular DNA
      repair processes. In vertebrate cells, telomeres consist of several kilobase
      pairs of DNA having the sequence TTAGGG, a few hundred base pairs of single
      stranded DNA at the 3' end of the telomeric DNA tract, and a host of proteins
      that organize the telomeric double and single-stranded DNA into a protective
      structure. Functional telomeres are essential for maintaining the integrity and
      stability of genomes. When combined with loss of cell cycle checkpoint controls,
      telomere dysfunction can lead to genomic instability, a common cause and hallmark
      of cancer. Consequently, normal mammalian cells respond to dysfunctional
      telomeres by undergoing apoptosis (programmed cell death) or cellular senescence
      (permanent cell cycle arrest), two cellular tumor suppressor mechanisms. These
      tumor suppressor mechanisms are potent suppressors of cancer, but recent evidence
      suggests that they can antagonistically also contribute to aging phenotypes.
      Here, we review what is known about the structure and function of telomeres in
      mammalian cells, particularly human cells, and how telomere dysfunction may arise
      and contribute to cancer and aging phenotypes.

PMID- 15743674
TI  - Telomere dysfunction in aging and cancer.
AB  - Telomeres are unique DNA-protein structures that contain noncoding TTAGGG repeats
      and telomere-associated proteins. These specialized structures are essential for
      maintaining genomic integrity. Alterations that lead to the disruption of
      telomere maintenance result in chromosome end-to-end fusions and/or ends being
      recognized as double-strand breaks. A large body of evidence suggests that the
      cell responds to dysfunctional telomeres by undergoing senescence, apoptosis, or
      genomic instability. In conjunction with other predisposing mechanisms, the
      genomic instability encountered in preimmortal cells due to dysfunctional or
      uncapped telomeres might lead to cancer. Furthermore, telomere dysfunction has
      been proposed to play critical roles in aging as well as cancer progression.
      Conversely, recent evidence has shown that targeting telomere maintenance
      mechanisms and inducing telomere dysfunction in cancer cells by inhibiting
      telomerase can lead to catastrophic events including rapid cell death and
      increased sensitivity to other cancer therapeutics. Thus, given the major role
      telomeres play during development, it is important to continue our understanding
      telomere structure, function and maintenance. Herein, we provide an overview of
      the emerging knowledge of telomere dysfunction and how it relates to possible
      links between aging and cancer.

PMID- 15743675
TI  - Chromosome instability in neoplasia: chaotic roots to continuous growth.
AB  - Multiple rearrangements of chromosome number and structure are common
      manifestations of genomic instability encountered in mammalian tumors. In
      neoplasia, in continuous immortalized growth in vitro, and in animal models, the
      accumulation of various defects on DNA repair and telomere maintenance
      machineries, mitotic spindle abnormalities, and breakage-fusion-bridge cycles,
      deteriorate the precise mitotic distribution of the genomic content, thus
      producing various types of chromosomal anomalies. These lesions generate
      tremendous genomic imbalances, which are evolutionary selected, since they force
      the function of the whole genome towards continuous growth. For more than a
      century chromosomal rearrangements and aneuploidy in neoplasia have been
      discussed and a vast number of genes and pathways, directly or indirectly
      implicated, have been described. In this review, we focus on the biological
      mechanisms that generate numerical or structural deviations of the normal diploid
      chromosomal constitution in epithelial neoplasia. There is growing evidence that
      chromosomal instability is both an epiphenomenon and a leading cause of cancer.
      We will discuss the roles of genes, chromosome structure, and telomere
      dysfunction in the initiation of chromosomal instability. We will explore
      research strategies that can be applied to identify rates of chromosomal
      instability in a specimen, and the putative biological consequences of karyotypic
      heterogeneity. Finally, we will re-examine the longstanding hypothesis of the
      generation of aneuploidy in the context of telomere dysfunction and restoration.

PMID- 15743673
TI  - A mouse model of Werner Syndrome: what can it tell us about aging and cancer?
AB  - The molecular mechanisms involved in mammalian aging and the consequent organ
      dysfunction/degeneration pathologies are not well understood. Studies of
      progeroid syndromes such as Werner Syndrome have advanced our understanding of
      how certain genetic pathways can influence the aging process on both cellular and
      molecular levels. In addition, improper maintenance of telomere length and the
      consequent cellular responses to dysfunctional telomeres have been proposed to
      promote replicative senescence that impact upon the onset of premature aging and
      cancer. Recent studies of the telomerase-Werner double null mouse link telomere
      dysfunction to accelerated aging and tumorigenesis in the setting of Werner
      deficiency. This mouse model thus provides a unique genetic platform to explore
      molecular mechanisms by which telomere dysfunction and loss of WRN gene function
      leads to the onset of premature aging and cancer.

PMID- 15743676
TI  - Molecular mechanisms of TNF-alpha-induced apoptosis in aging human T cell
      subsets.
AB  - TNF-alpha, a pro-inflammatory cytokine, exerts its biological activity by
      signaling via its two receptors, TNFR-1 and TNFR-2 and by activating NF-kappaB.
      NF-kappaB is essential for survival of many cell types; however, TNF-alpha also
      induces cell death. During human aging TNF-alpha production and TNF-alpha-induced
      apoptosis are increased. In this brief review, we will discuss the TNF-alpha
      mediated signaling and various molecular mechanisms underlying increased
      apoptosis in T cell subsets in aged humans with a special reference to
      alterations in transcription factor NF-kappaB and Fas-associated death domain
      (FADD).

PMID- 15743677
TI  - The emerging role of poly(ADP-ribose) polymerase-1 in longevity.
AB  - In the present paper, the involvement of the family of poly(ADP-ribose)
      polymerases (PARPs), and especially of PARP-1, in mammalian longevity is
      reviewed. PARPs catalyse poly(ADP-ribosyl)ation, a covalent post-translational
      protein modification in eukaryotic cells. PARP-1 and PARP-2 are activated by DNA
      strand breaks, play a role in DNA base-excision repair (BER) and are survival
      factors for cells exposed to low doses of ionising radiation or alkylating
      agents. PARP-1 is the main catalyst of poly(ADP-ribosyl)ation in living cells
      under conditions of DNA breakage, accounting for about 90% of cellular poly(ADP
      ribose). DNA-damage-induced poly(ADP-ribosyl)ation also functions as a negative
      regulator of DNA damage-induced genomic instability. Cellular poly(ADP
      ribosyl)ation capacity in permeabilised mononuclear blood cells (MNC) is
      positively correlated with life span of mammalian species. Furthermore PARP-1
      physically interacts with WRN, the protein deficient in Werner syndrome, a human
      progeroid disorder, and PARP-1 and WRN functionally cooperate in preventing
      carcinogenesis in vivo. Some of the other members of the PARP family have also
      been revealed as important regulators of cellular functions relating to
      ageing/longevity. In particular, tankyrase-1, tankyrase-2, PARP-2 as well as PARP
      1 have been found in association with telomeric DNA and are able to poly(ADP
      ribosyl)ate the telomere-binding proteins TRF-1 and TRF-2, thus blocking their
      DNA-binding activity and controlling telomere extension by telomerase.

PMID- 15743678
TI  - Function of the ING family of PHD proteins in cancer.
AB  - The ING genes encode a family of at least seven proteins with conserved plant
      homeodomain (PHD)-type zinc fingers in their C-termini. The founding member,
      ING1, is capable of binding to and affecting the activity of histone
      acetyltransferase (HAT), histone deacetylase (HDAC), and factor acetyltransferase
      (FAT) protein complexes. Some ING proteins are involved in transcriptional
      regulation of genes, such as the p53-inducible genes p21 and Bax. Others have
      been found to affect post-translational modifications, exemplified by the ING2
      induced acetylation of p53 on the same site deacetylated by the Sir2 HDAC. Upon
      UV irradiation, ING1 causes cell cycle arrest and interacts with proliferating
      cell nuclear antigen to promote DNA repair or induce apoptosis in cells to
      prevent tumorigenesis depending upon the severity of DNA damage. It is very
      likely that, by linking DNA repair, apoptosis and chromatin remodeling to the
      transcriptional regulation of critical genes, ING1 exerts it tumor suppressor
      functions by helping maintain genomic stability. Therefore, ING proteins, which
      are down-regulated in a broad variety of cancer types, are able to restrict cell
      growth and proliferation, induce apoptosis, and modulate cell cycle progression,
      which strongly supports the notion that ING family proteins act as class II tumor
      suppressors.

PMID- 15743679
TI  - Potential oncogenic action of tenascin-C in tumorigenesis.
AB  - The prominent expression of tenascin-C in the stroma of most solid tumors, first
      observed in the mid 1980s, implicates tenascin-C in tumorigenesis. This is also
      supported by in vitro experiments that demonstrate the capacity of tenascin-C to
      stimulate tumor growth by various mechanisms including promotion of
      proliferation, escaping immuno-surveillance and positively influencing
      angiogenesis. However, tumorigenesis in tenascin-C knock-out mice is not
      significantly different from that observed in control animals. Perhaps this is
      not unexpected if one considers that tenascin-C may act as an oncogene. The
      potential role of tenascin-C in tumorigenesis through its oncogenic action on
      cellular signaling will be discussed in this review, including how tenascin-C
      mediated tumor cell detachment might affect genome stability.

PMID- 15743680
TI  - Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia
      versus sarcopenia.
AB  - The aim of the present review is to summarize and evaluate the different
      mechanisms and catabolic mediators involved in cancer cachexia and ageing
      sarcopenia since they may represent targets for future promising clinical
      investigations. Cancer cachexia is a syndrome characterized by a marked weight
      loss, anorexia, asthenia and anemia. In fact, many patients who die with advanced
      cancer suffer from cachexia. The degree of cachexia is inversely correlated with
      the survival time of the patient and it always implies a poor prognosis.
      Unfortunately, at the clinical level, cachexia is not treated until the patient
      suffers from a considerable weight loss and wasting. At this point, the cachectic
      syndrome is almost irreversible. The cachectic state is often associated with the
      presence and growth of the tumour and leads to a malnutrition status due to the
      induction of anorexia. In recent years, age-related diseases and disabilities
      have become of major health interest and importance. This holds particularly for
      muscle wasting, also known as sarcopenia, that decreases the quality of life of
      the geriatric population, increasing morbidity and decreasing life expectancy.
      The cachectic factors (associated with both depletion of fat stores and muscular
      tissue) can be divided into two categories: of tumour origin and humoural
      factors. In conclusion, more research should be devoted to the understanding of
      muscle wasting mediators, both in cancer and ageing, in particular the
      identification of common mediators may prove as a good therapeutic strategies for
      both prevention and treatment of wasting both in disease and during healthy
      ageing.

PMID- 15743681
TI  - Molecular cloning and functional characterization of zebrafish ATM.
AB  - Ataxia-telangiectasia mutated (ATM) is the gene product mutated in ataxia
      telangiectasia (A-T), which is an autosomal recessive disorder with symptoms
      including neurodegeneration, cancer predisposition and premature aging. ATM is
      thought to play a pivotal role in signal transduction in response to genotoxic
      DNA damage. To study the physiological and developmental functions of ATM using
      the zebrafish model system, we cloned the zebrafish homolog cDNA of human ATM
      (hATM), zebrafish ATM (zATM), analyzed the expression pattern of zATM during
      early development, and further developed the system to study loss of zATM
      function in zebrafish embryos. Employing information available from the zebrafish
      genomic database, we utilized a PCR-based approach to isolate zATM cDNA clones.
      Sequence analysis of zATM showed a high level homology in the functional domains
      of hATM. The putative FAT, phosphoinositide 3-kinase-like, and FATC domains of
      zATM, which regulate ATM kinase activity and functions, were the most highly
      conserved regions, exhibiting 64-94% amino acid identity to the corresponding
      domains in hATM, while exhibiting approximately 50% amino acid identity outside
      these domains. The zATM gene is expected to consist of 62 coding exons, and we
      have identified at least 55 exons encompassing more than 100kb of nucleotide
      sequence, which encodes about 9 kb of cDNA. By in situ hybridization, zATM mRNA
      was detected ubiquitously with a dramatic increase at the 18-somite stage, then
      more specifically in the eye, brain, trunk, and tail at later stages. To inhibit
      zATM expression and function, we designed and synthesized splice-blocking
      antisense-morpholino oligonucleotides targeting the phosphoinositide 3-kinase
      like domain. We demonstrated that this knockdown of zATM caused abnormal
      development upon ionizing radiation-induced DNA damage. Our data suggest that the
      ATM gene is structurally and functionally conserved in vertebrates from zebrafish
      to human.

PMID- 15743682
TI  - Insulin in aging and cancer: antidiabetic drug Diabenol as geroprotector and
      anticarcinogen.
AB  - The effects of new antidiabetic drug Diabenol (9-beta-diethylaminoethyl-2,3
      dihydroimidazo-(1,2-alpha)benzimidazol dihydrochloride) on life span and
      spontaneous tumor incidence in NMRI and transgenic HER-2/neu mice as well as on
      colon carcinogenesis induced by 1,2-dimethylhydrazine in rats are studied. It is
      shown that treatment with the drug failed influence body weight gain dynamics,
      food and water consumption and the body temperature, slowed down age-related
      disturbances in estrous function and increased life span of all and 10% most long
      living NMRI mice. The treatment with Diabenol inhibited spontaneous tumor
      incidence and increased the mammary tumor latency in these mice. Diabenol
      treatment slowed down age-related changes in estrous function in HER-2/neu mice,
      failed influence survival of these mice and slightly inhibited the incidence and
      decreased the size of mammary adenocarcinoma metastases into the lung. In rats
      exposed to 1,2-dimethylhydrazine, treatment with Diabenol significantly inhibited
      multiplicity of all colon tumors, decreased by 2.2 times the incidence of
      carcinomas in ascending colon and by 3.1 times their multiplicity. Treatment with
      Diabenol was followed by higher incidence of exophytic and well-differentiated
      colon tumors as compared with the control rats exposed to the carcinogen alone
      (76.3% and 50%, and 47.4% and 14.7%, respectively). Thus, the drug increases
      survival and inhibits spontaneous carcinogenesis in mice and inhibits colon
      carcinogenesis in rats.

PMID- 15743683
TI  - Activation of nuclear factor-kappaB (NFkappaB) identifies a high-risk subset of
      hormone-dependent breast cancers.
AB  - Activation of nuclear factor-kappaB (NFkappaB) has been linked to the development
      of hormone-independent, estrogen receptor (ER)-negative human breast cancers. To
      explore the possibility that activated NFkappaB marks a subset of clinically more
      aggressive ER-positive breast cancers, NFkappaB DNA-binding was measured in ER
      positive breast cancer cell lines and primary breast cancer extracts by
      electrophoretic mobility shift assay and ELISA-based quantification of specific
      NFkappaB p50 and p65 DNA-binding subunits. Oxidant (menadione 100 microMx30 min)
      activation of NFkappaB was prevented by pretreatment with various NFkappaB
      inhibitors, including the specific IkappaB kinase (IKK) inhibitor, parthenolide
      (PA), which was found to sensitize MCF-7/HER2 and BT474 but not MCF-7 cells to
      the antiestrogen tamoxifen. Early stage primary breast cancers selected a priori
      for lower ER content (21-87 fmol/mg; n=59) and known clinical outcome showed two-
      to four-fold increased p50 and p65 NFkappaB DNA-binding over a second set of
      primary breast cancers with higher ER content (>100 fmol/mg; n=22). Breast
      cancers destined to relapse (13/59) showed significantly higher NFkappaB p50 (but
      not p65) DNA-binding over those not destined to relapse (46/59; p=0.04). NFkappaB
      p50 DNA-binding correlated positively with several prognostic biomarkers;
      however, only NFkappaB p50 DNA-binding (p=0.04), Activator Protein-1 DNA-binding
      (AP-1; p<or=0.01) and urokinase-type plasminogen activator expression (uPA;
      p=0.0014) showed significant associations with metastatic relapse and disease
      free patient survival. These clinical findings indicate that high-risk ER
      positive breast cancers may be prognostically identified by increased NFkappaB
      p50 DNA-binding, and support preclinical models suggesting that therapeutic
      inhibition of NFkappaB activation may improve the endocrine responsiveness of
      high-risk ER-positive breast cancers.

PMID- 15743685
TI  - Increased nitric oxide levels and iNOS over-expression in oral squamous cell
      carcinoma.

PMID- 15743686
TI  - A review on re-irradiation for recurrent and second primary head and neck cancer.
AB  - The purpose of this paper is to review the results of studies regarding radiation
      as primary or adjuvant treatment modality for head and neck recurrences or second
      primary tumours (SPT) in previously irradiated areas, with emphasis on acute and
      late radiation induced morbidity, locoregional control and survival. The criteria
      for the studies to be included in this review were: (1) re-irradiation for
      locoregional recurrent disease or SPT in the head and neck region, (2) squamous
      cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx, and (3) a
      minimum of 10 patients included in the study. Studies were divided in four
      categories, including (1) external beam re-irradiation, (2) re-irradiation with
      brachytherapy, (3) re-irradiation in combination with chemotherapy and (4)
      postoperative re-irradiation. Most studies were retrospective using heterogeneous
      treatment regimens and including heterogeneous groups of patients. A total number
      of 27 studies were included. Overall survival, locoregional control and acute and
      late radiation-induced morbidity are reported. High dose reirradiation as salvage
      treatment in case of recurrent or second primary head and neck cancer should be
      considered, particularly when salvage surgery is not feasible. Although long term
      survivors are reported is some studies, the relatively high incidence of
      treatment-related morbidity emphasize the need for further optimisation in order
      to improve locoregional control and reduce the risk on late morbidity.

PMID- 15743687
TI  - Tobacco, oral cancer, and treatment of dependence.
AB  - Tobacco dependence is recognised as a life-threatening disorder with serious oral
      health consequences which responds to treatment in the form of behavioural
      support and medication. While cigarette smoking is the most hazardous and
      prevalent form of tobacco use in the west, consideration also needs to be given
      to other forms such as bidi smoking in India, reverse smoking by several rural
      populations and use of snuff and chewing tobacco. The evidence that the use of
      tobacco is the major risk factor for oral cancer and potentially malignant
      lesions of the mouth is clear. Counseling to quit smoking is not applied in a
      systematic or frequent manner to people presenting with potentially malignant
      lesions of the oral cavity. This review makes recommendations for interventions
      by health professionals to encourage and aid cessation of tobacco use as a part
      of prevention of oral cancer.

PMID- 15743688
TI  - Increased nitric oxide levels and iNOS over-expression in oral squamous cell
      carcinoma.
AB  - Inducible nitric oxide synthase (iNOS) is responsible for generating high levels
      of nitric oxide (NO) in tissues. Increased iNOS expression has been demonstrated
      in a number of carcinomas including head and neck squamous cell carcinoma (SCC).
      However, iNOS levels have not been evaluated specifically in oral cavity SCC, or
      in the precancerous lesions that progress to oral SCC. Also, NO levels have not
      been measured in oral precancerous or cancerous tissues. We therefore measured
      iNOS mRNA, iNOS protein and NO in oral SCC, oral dysplasias and normal oral
      epithelium. We used RT-PCR to quantify and compare iNOS mRNA levels in these oral
      tissue specimens. We found that iNOS mRNA was overexpressed in 41% of oral SCC
      but in only 8% of dysplasia specimens (P = 0.003). Immunohistochemistry was used
      to evaluate iNOS protein levels in oral SCC, oral dysplasias and normal oral
      epithelium. A significantly higher percentage of oral SCC specimens showed the
      highest level of iNOS staining relative to the oral dysplasias and normal oral
      epithelial samples (95% of oral SCC, 50% of dysplasias, and only 0% of normal
      epithelial controls, P < 0.0001). The positive staining for iNOS was limited to
      the SCC cells. Production of NO from iNOS was quantified using HPLC and found to
      be significantly higher in oral SCC (1.45 +/- 0.56 microg/ml) than normal
      epithelial controls (0.43 +/- 0.26 microg/ml) (P = 0.0013). We conclude that iNOS
      mRNA levels and NO production are significantly increased, in oral SCC compared
      to oral dysplasias and normal epithelial controls. These findings suggest that
      increased iNOS expression and the generation of high NO levels might have a role
      in oral SCC development.

PMID- 15743689
TI  - Overexpression of cyclin D1 and interaction between p27Kip1 and tumour thickness
      predict lymph node metastases occurrence in lower lip squamous cell carcinoma.
AB  - We have attempted to identify those subgroups of patients most likely to develop
      lymph node metastases from squamous cell carcinoma of the lower lip (LLSSC). A
      total of 97 subjects, who did not undergo elective neck dissection, were
      recruited into the 60-month disease-free survival study. After univariate
      analysis, tumour size, histological grading, maximal thickness, perineural
      invasion and immunoreactivity to cyclin D1 and p27Kip1 proteins proved to be
      significant factors. Tests of the effect of interaction between p27Kip1 LI and
      tumour thickness yielded that the impact of tumour thickness on the risk of lymph
      node metastases was modified by the percentage of p27Kip1 positive cells.
      Subsequent to models of multivariate analysis, tumour size, positive cyclin D1
      protein expression, maximal thickness (> 5 mm), p27Kip1 LI (%) and the
      interaction term between p27Kip1 LI and tumour thickness retained strong
      independent predictive values for lymph node metastases. We suggest that
      immunohistochemistry for cyclin D1 and p27Kip1 may prove to be valuable ancillary
      tests for identifying LLSSC with metastatic potential.

PMID- 15743690
TI  - Evaluation of TS-1 based treatment and expression of thymidylate synthase and
      dihydropyrimidine dehydrogenase on oral squamous cell carcinoma.
AB  - Seventeen oral squamous cell carcinoma (SCC) patients underwent chemotherapy with
      TS-1 (8 males and 9 females, mean age; 75.1 years, range; 47-102 years). TS-1
      permitted five cases of oral chemotherapy on an outpatient basis and 8 cases in
      elder patients over 80-years of age. Excepting five patients who underwent TS-1
      therapy as post-operative adjuvant chemotherapy, the therapeutic efficacy of TS-1
      in 12 patients with or without irradiation, surgery or chemotherapy resulted in 3
      cases of complete response (CR), 6 cases of partial response (PR), 3 cases of
      stable disease (SD), with no progressive disease (PD) cases (overall response
      rate; 75%). SCC samples obtained from biopsy were immunohistochemically stained
      with anti-TS and DPD polyclonal antibody. Although the statistical significance
      was not clear, the expression of TS and DPD for CR cases was lower than that for
      SD cases. TS-1 therapy improved quality of life (QOL) especially in elder
      patients with oral SCC, and our immunohistochemical results suggested the
      predictive possibilities of TS and DPD expression in response to TS-1.

PMID- 15743691
TI  - Expression and clinical significance of matrix metalloproteinase-2 and matrix
      metalloproteinase-9 in oral squamous cell carcinoma.
AB  - To successfully establish a metastasis from an invasive carcinoma, the first step
      involves the degradation of the underlying basement membrane, which is mainly
      made up of type IV collagen. Matrix metalloproteinases (MMPs)-2 and -9 are
      thought to play an important role in its degradation because of their ability to
      destroy this type of collagen. In order to evaluate the prognostic significance
      of these proteases, we studied the expression of MMP-2 and -9 in series of 68
      OSCC by immunohistochemistry. Of the oral carcinomas, 28% (n = 19) expressed MMP
      2, and 17.6% (n = 12) expressed MMP-9. MMP-2 immunoreactivity was significantly
      higher in patients with alcohol consumption (p = 0.028) (OR = 4), and in those
      younger than 60 years (p = 0.041). MMP-9 immunostaining showed statistically
      significant association with the tumor grade of differentiation (p = 0.019), the
      T-stage (p = 0.05), and also with the alcohol intake (p = 0.04) (OR = 7.67). In
      the present study, although not statistically significant, we observed that
      immunoexpression of MMP-2 and MMP-9 was stronger in patients with lymph node
      metastasis (OR = 1.65 and 2.29, respectively). In patients without regional lymph
      node metastasis, positive MMP-9 immunostaining was related to poor survival rates
      (p = 0.02; OR = 5.8). MMP-2 and -9 are involved in the invasion process of oral
      cancer, and MMP-9 is related to poor prognosis in the subset of patients without
      neck node metastasis. Ethanol could enhance the carcinogenetic process in oral
      cavity through its influence in the expression of MMP-2 and -9.

PMID- 15743692
TI  - Multivariate analysis of risk factors for wound infection in head and neck
      squamous cell carcinoma surgery with opening of mucosa. Study of 260 surgical
      procedures.
AB  - The goal of this prospective study was to determine risk factors for wound
      infections (WI) for patients with head and neck cancer who had undergone surgical
      procedures with opening of upper aerodigestive tract mucosa in multimodal
      therapeutic approaches. Two hundred and sixty consecutive surgical procedures
      were studied at Oscar Lambret Cancer Center over a 36-month period. Twenty-five
      variables were recorded for each patient. Statistical evaluation used chi2 test
      analysis (categorical data) and Mann-Whitney test (continuous variables).
      Multivariate analysis was performed with logistic regression model. The overall
      rate of WI was 45% (117/260). Univariate analysis indicated that five variables
      were significantly related to the likelihood of WI: male sex (p = 0.03), previous
      chemotherapy (p = 0.009), duration of previous hospital stay (p = 0.013),
      hypopharyngeal location (p = 0.003), post-laryngectomy tracheostoma (p < 0.001).
      Multivariate analysis identified only one major risk factor for WI: post
      laryngectomy tracheostoma (Odd Ratio 1.9 [95% CI 1.3-3]; 33% versus 64%; p =
      0.001). Despite antibiotic prophylaxis, WI occurrence is high. This study
      identified one major risk factor, post-laryngectomy tracheostomy. Long-term
      curative antibiotherapy must be evaluated in cancer head and neck surgery
      requiring post-laryngectomy tracheostoma.

PMID- 15743693
TI  - Cyclo-oxygenase-1 and -2 expression in human oral mucosa, dysplasias and squamous
      cell carcinomas and their pathological significance.
AB  - Cyclo-oxygenase (COX) is a key enzyme in the conversion of arachidonic acid to
      prostanoids. The expression of its isoforms, COX-1 and -2 is found in many human
      malignancies. This study analyzed the correlation between COX expression and the
      pathobiological nature of human oral mucosa, dysplasias and squamous cell
      carcinomas (SCCs). We examined 9 specimens of normal oral epithelia, 65 lesions
      with dysplasias and 50 SCCs. Labeling indices (LIs) for COX-1, COX-2, Ki-67 and
      P53, microvessel density (MVD) and apoptotic index (AI) were evaluated using
      immunohistochemistry and TUNEL methods. Western blot analysis of COX-1 and -2 was
      performed on four human oral SCC cell lines, all of which showed expression. The
      LIs for COX-1 and -2 were higher for the dysplasias than the SCCs. LIs of COX-2
      but not COX-1 correlated with the histological grade of dysplasia, being highest
      for the severe dysplasias (p < 0.05). In contrast, the COX-2 LIs as well as COX-1
      were significantly (p < 0.05) inversely correlated with the histological
      differentiation of the SCCs. COX-2 expression was significantly correlated with
      LIs of COX-1 for dysplasia (p < 0.05), but not for the SCCs. In addition no
      significant relationship was noted between COX-2 expression and the Lis of Ki-67,
      P53, AI as well as MVD for the dysplasias and SCCs. The expression of COX-1 and 
      2 is correlated with early stage tumorigenesis and cellular differentiation of
      SCCs in the oral dysplasia-carcinoma sequence.

PMID- 15743694
TI  - Patient and tumour factors associated with advanced carcinomas of the head and
      neck.
AB  - This study identifies patient and tumour related factors associated with advanced
      carcinoma of the head and neck. Special attention was paid to the role of patient
      and professional diagnostic delays. Three-hundred and six patients newly
      diagnosed with carcinoma of the pharynx, larynx and oral cavity were included in
      the study. Logistic regression analyses were used to identify the risk factors
      for presenting with an advanced tumour. Multivariate analysis found that having a
      pharyngeal carcinoma (OR 22.68; p = .000), an oral carcinoma (OR 6.51; p = .000),
      or a supraglottic carcinoma (OR 8.12; p = .000), patient delay > 3 months (OR
      3.47; p = .001) and having a doctors' contact for another reason than the head
      and neck symptom (OR 0.20; p = .022) were predictive of presenting with an
      advanced tumour. These results suggest that beyond tumour-related factors, the
      patients' care seeking behaviour contributes to an increased risk of being
      diagnosed with an advanced tumour of the head and neck.

PMID- 15743695
TI  - Prognostic impact of the epidermal growth factor receptor levels for patients
      with larynx and hypopharynx cancer.
AB  - The aim of this study was to analyse prognostic factors for disease free interval
      (DFI) and overall survival (OS) among patients with larynx and hypopharynx cancer
      requiring a total laryngectomy. Three groups of patients were studied according
      to the type of treatment they received. Fifty-eight patients had total
      laryngectomy, 71 patients had organ preservation treatment including induction
      chemotherapy followed by exclusive radiotherapy, 26 patients received induction
      chemotherapy followed by salvage total laryngectomy. The studied potential
      prognostic factors were age, gender, performans status, primary tumor
      localization, T status, N status, tumor volume and tumoral EGFR level (fmol/mg
      protein). The multivariate analysis showed that both N status and tumor volume
      were significant for DFI and OS. EGFR level was significant only for patients
      treated by induction chemotherapy and exclusive radiotherapy (p = 0.05 and 0.05
      for DFI and OS length, respectively). Among this group, patients with tumor EGFR
      levels lower and higher than 100 fmol/mg protein had 53% versus 22% and 51%
      versus 18% 5-year of DFI and OS rates, respectively (Log rank test: p = 0.001 and
      0.0001). EGFR determination appears to be a powerful prognostic parameter for
      patients treated by induction chemotherapy followed by exclusive radiotherapy.
      Laryngectomy seems to erase the prognostic impact of EGFR expression. These
      results profile the use of EGFR targeting therapy for this category of patients.

PMID- 15743696
TI  - Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23
      patients and review of the literature.
AB  - Adenoid cystic carcinoma (ACC) is a rare epithelial tumor with a distinct natural
      history characterized by an indolent but persistent growth, late onset of distant
      metastases and eventual death of patients. Between 1991 and 2003, 23 patients
      with ACC were treated in our Department. Surgery with a curative intent followed
      by radiotherapy (RT) was applied in 22 patients. Complete resection was achieved
      in 72.73% of patients. Local recurrence occurred in 26% of patients. Positive
      margins emerged as the only statistically significant parameter (p < 0.0001)
      influencing the development of local recurrence. Distant metastasis (DM) occurred
      in 47.8% of patients. In 54.5% of the patients developing DM, this occurred
      between 5 and 10 years after the initial treatment. DM was influenced by
      perineural invasion (p = 0.04) and was disassociated from local control of the
      tumor. The mean overall survival of our patients was 70.58 months and the mean
      disease free survival 61.85 months. Perineural invasion (p = 0.048) and DM (p =
      0.001) had a statistically significant impact on final patients' outcome. The
      most important factor influencing survival was DM. Its late onset, irrespectively
      of local control, supports the hypothesis that ACC has a potential to develop DM
      in the very early phases of tumor growth.

PMID- 15743697
TI  - Lakes in crisis.

PMID- 15743698
TI  - Pesticide spraying and health effects.

PMID- 15743699
TI  - "Epidemiology of health effects of radiofrequency exposure".

PMID- 15743700
TI  - Potential selection biases.

PMID- 15743702
TI  - Listing occupational carcinogens.

PMID- 15743701
TI  - David Rall and the national toxicology program.

PMID- 15743703
TI  - Streamside solution.

PMID- 15743706
TI  - The Great Lakes: awash in policies.

PMID- 15743704
TI  - Great lakes: resource at risk.

PMID- 15743707
TI  - An ounce of prevention from a ton of tomatoes.

PMID- 15743709
TI  - Can lessons from public health disease surveillance be applied to environmental
      public health tracking?
AB  - Disease surveillance has a century-long tradition in public health, and
      environmental data have been collected at a national level by the U.S.
      Environmental Protection Agency for several decades. Recently, the Centers for
      Disease Control and Prevention announced an initiative to develop a national
      environmental public health tracking (EPHT) network with "linkage" of existing
      environmental and chronic disease data as a central goal. On the basis of
      experience with long-established disease surveillance systems, in this article we
      suggest how a system capable of linking routinely collected disease and exposure
      data should be developed, but caution that formal linkage of data is not the only
      approach required for an effective EPHT program. The primary operational goal of
      EPHT has to be the "treatment" of the environment to prevent and/or reduce
      exposures and minimize population risk for developing chronic diseases. Chronic,
      multifactorial diseases do not lend themselves to data-driven evaluations of
      intervention strategies, time trends, exposure patterns, or identification of at
      risk populations based only on routinely collected surveillance data. Thus, EPHT
      should be synonymous with a dynamic process requiring regular system updates to
      a) incorporate new technologies to improve population-level exposure and disease
      assessment, b) allow public dissemination of new data that become available, c)
      allow the policy community to address new and emerging exposures and disease
      "threads," and d) evaluate the effectiveness of EPHT over some appropriate time
      interval. It will be necessary to weigh the benefits of surveillance against its
      costs, but the major challenge will be to maintain support for this important new
      system. Key words: environmental health, evaluation, intervention, registries,
      surveillance.

PMID- 15743710
TI  - Urinary trivalent methylated arsenic species in a population chronically exposed
      to inorganic arsenic.
AB  - Chronic exposure to inorganic arsenic (iAs) has been associated with increased
      risk of various forms of cancer and of noncancerous diseases. Metabolic
      conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII)
      and dimethylarsinite (DMAsIII) may play a significant role in determining the
      extent and character of toxic and cancer-promoting effects of iAs exposure. In
      this study we examined the relationship between urinary profiles of MAsIII and
      DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in
      drinking water. The study subjects were recruited among the residents of an
      endemic region of central Mexico. Drinking-water reservoirs in this region are
      heavily contaminated with iAs. Previous studies carried out in the local
      populations have found an increased incidence of pathologies, primarily skin
      lesions, that are characteristic of arseniasis. The goal of this study was to
      investigate the urinary profiles for the trivalent and pentavalent As metabolites
      in both high- and low-iAs-exposed subjects. Notably, methylated trivalent
      arsenicals were detected in 98% of analyzed urine samples. On average, the major
      metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV
      (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More
      important, the average MAsIII concentration was significantly higher in the urine
      of exposed individuals with skin lesions compared with those who drank iAs
      contaminated water but had no skin lesions. These data suggest that urinary
      levels of MAsIII, the most toxic species among identified metabolites of iAs, may
      serve as an indicator to identify individuals with increased susceptibility to
      toxic and cancer-promoting effects of arseniasis.

PMID- 15743711
TI  - Occupational exposure to crystalline silica dust in the United States, 1988-2003.
AB  - The purposes of this study were a) to summarize measurements of airborne
      (respirable) crystalline silica dust exposure levels among U.S. workers, b) to
      provide an update of the 1990 Stewart and Rice report on airborne silica exposure
      levels in high-risk industries and occupations with data for the time period 1988
      2003, c) to estimate the number of workers potentially exposed to silica in
      industries that the Occupational Safety and Health Administration (OSHA)
      inspected for high exposure levels, and d) to conduct time trend analyses on
      airborne silica dust exposure levels for time-weighted average (TWA)
      measurements. Compliance inspection data that were taken from the OSHA Integrated
      Management Information System (IMIS) for 1988-2003 (n = 7,209) were used to
      measure the airborne crystalline silica dust exposure levels among U.S. workers.
      A second-order autoregressive model was applied to assess the change in the mean
      silica exposure measurements over time. The overall geometric mean of silica
      exposure levels for 8-hr personal TWA samples collected during programmed
      inspections was 0.077 mg/m3, well above the applicable American Conference of
      Governmental Industrial Hygienists threshold limit value of 0.05 mg/m3. Surgical
      appliances supplies industry [Standard Industrial Classification (SIC) 3842] had
      the lowest geometric mean silica exposure level of 0.017 mg/m3, compared with the
      highest level, 0.166 mg/m3, for the metal valves and pipe fitting industry (SIC
      3494), for an 8-hr TWA measurement. Although a downward trend in the airborne
      silica exposure levels was observed during 1988-2003, the results showed that
      3.6% of the sampled workers were exposed above the OSHA-calculated permissible
      exposure limit.

PMID- 15743712
TI  - Intersexuality and the cricket frog decline: historic and geographic trends.
AB  - Exposure to anthropogenic endocrine disruptors has been listed as one of several
      potential causes of amphibian declines in recent years. We examined gonads of 814
      cricket frogs (Acris crepitans) collected in Illinois and deposited in museum
      collections to elucidate relationships between the decline of this species in
      Illinois and the spatial and temporal distribution of individuals with intersex
      gonads. Compared with the preorganochlorine era studied (1852-1929), the
      percentage of intersex cricket frogs increased during the period of industrial
      growth and initial uses of polychlorinated biphenyls (PCBs) (1930-1945), was
      highest during the greatest manufacture and use of p,p
      dichlorodiphenyltrichloroethane (DDT) and PCBs (1946-1959), began declining with
      the increase in public concern and environmental regulations that reduced and
      then prevented sales of DDT in the United States (1960-1979), and continued to
      decline through the period of gradual reductions in environmental residues of
      organochlorine pesticides and PCBs in the midwestern United States (1980-2001).
      The proportion of intersex individuals among those frogs was highest in the
      heavily industrialized and urbanized northeastern portion of Illinois,
      intermediate in the intensively farmed central and northwestern areas, and lowest
      in the less intensively managed and ecologically more diverse southern part of
      the state. Records of deposits of cricket frog specimens into museum collections
      indicate a marked reduction in numbers from northeastern Illinois in recent
      decades. These findings are consistent with the hypothesis that endocrine
      disruption contributed to the decline of cricket frogs in Illinois.

PMID- 15743713
TI  - Mercury in commercial fish: optimizing individual choices to reduce risk.
AB  - Most attention to the risks from fish consumption has focused on recreational
      anglers and on fish caught by individuals, but the majority of fish that people
      eat are purchased from commercial sources. We examined mercury levels in three
      types of fish (tuna, flounder, bluefish) commonly available in New Jersey stores,
      sampling different regions of the state, in communities with high and low per
      capita incomes, and in both supermarkets and specialty fish markets. We were
      interested in species-specific levels of mercury in New Jersey fish and whether
      these levels were similar to data generated nationally by the Food and Drug
      Administration (FDA; mainly from 1990 to 1992) on the same types of fish. Such
      information is critical for providing public health advice. We were also
      interested in whether mercury levels in three common species of fish differed by
      region of the state, economic neighborhood, or type of store. We found
      significant species differences, with tuna having the highest levels and flounder
      the lowest levels. There were no significant differences in mercury levels as a
      function of type of store or economic neighborhood. There was only one regional
      difference: flounder from fish markets along the Jersey shore had higher mercury
      levels than flounder bought in other markets. We also examined mercury levels in
      six other commonly available fish and two shellfish from central New Jersey
      markets. There were significant differences in availability and in mercury levels
      among fish and shellfish. Both shrimp and scallops had total mercury levels <
      0.02 ppm (wet weight). Large shrimp had significantly lower levels of mercury
      than small shrimp. For tuna, sea bass, croaker, whiting, scallops, and shrimp,
      the levels of mercury were higher in New Jersey samples than those reported by
      the FDA. Consumers selecting fish for ease of availability (present in > 50% of
      markets) would select flounder, snapper, bluefish, and tuna (tuna had the highest
      mercury value), and those selecting only for price would select whiting, porgy,
      croaker, and bluefish (all with average mercury levels < 0.3 ppm wet weight).
      Flounder was the fish with the best relationship among availability, cost, and
      low mercury levels. We suggest that state agencies responsible for protecting the
      health of their citizens should obtain information on fish availability in
      markets and fish preferences of diverse groups of citizens and use this
      information to select fish for analysis of contaminant levels, providing data on
      the most commonly eaten fish that will help people make informed decisions about
      risks from fish consumption.

PMID- 15743714
TI  - PCB exposure and in vivo CYP1A2 activity among Native Americans.
AB  - Cytochrome P-450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation
      of some carcinogens and is believed to be induced by xenobiotics. Very few
      studies, however, have investigated the association between environmental
      exposures and in vivo CYP1A2 activity in humans. To address this issue, a study
      was conducted of CYP1A2 activity among Native Americans exposed to
      polychlorinated biphenyls (PCBs) from the consumption of fish from the St.
      Lawrence River. At the Mohawk Nation at Akwesasne (in New York and in Ontario and
      Quebec, Canada), 103 adults were interviewed, and they donated blood for serum
      PCB analysis and underwent the caffeine breath test (CBT), a safe and noninvasive
      procedure that uses caffeine as a probe for CYP1A2 activity in vivo. The results
      supported the findings of other studies that CBT values are higher among smokers
      and men and lower among women who use oral contraceptives. Despite a relatively
      low average total PCB body burden in this population, the sum of serum levels for
      nine mono- or di-ortho-substituted PCB congeners showed positive associations
      with CBT values (p = 0.052 wet weight and p = 0.029 lipid adjusted), as did toxic
      equivalent quantities (TEQs; p = 0.091 for wet weight and 0.048 for lipid
      adjusted). Regarding individual congeners, serum levels of PCB-153, PCB-170, and
      PCB-180 were significantly correlated with CBT values. The results support the
      notion that CYP1A2 activity may be a marker of an early biological effect of
      exposure to PCBs in humans and that the CBT may be a useful tool to monitor such
      effects.

PMID- 15743715
TI  - Binding of estrogenic compounds to recombinant estrogen receptor-alpha:
      application to environmental analysis.
AB  - Estrogenic activity in environmental samples could be mediated through a wide
      variety of compounds and by various mechanisms. High-affinity compounds for
      estrogen receptors (ERs), such as natural or synthetic estrogens, as well as low
      affinity compounds such as alkylphenols, phthalates, and polychlorinated
      biphenyls are present in water and sediment samples. Furthermore, compounds such
      as polycyclic aromatic hydrocarbons, which do not bind ERs, modulate estrogen
      activity by means of the aryl hydrocarbon receptor (AhR). In order to
      characterize compounds that mediate estrogenic activity in river water and
      sediment samples, we developed a tool based on the ER-alphaligand-binding domain,
      which permitted us to estimate contaminating estrogenic compound affinities. We
      designed a simple transactivation assay in which compounds of high affinity were
      captured by limited amounts of recombinant ER-alpha and whose capture led to a
      selective inhibition of transactivation. This approach allowed us to bring to
      light that water samples contain estrogenic compounds that display a high
      affinity for ERs but are present at low concentrations. In sediment samples, on
      the contrary, we showed that estrogenic compounds possess a low affinity and are
      present at high concentration. Finally, we used immobilized recombinant ER-alpha
      to separate ligands for ER and AhR that are present in river sediments.
      Immobilized ER-alpha, which does not retain dioxin-like compounds, enabled us to
      isolate and concentrate ER ligands to facilitate their further analysis.

PMID- 15743716
TI  - Occupational exposure to carbofuran and the incidence of cancer in the
      Agricultural Health Study.
AB  - Carbofuran is a carbamate insecticide registered for use on a variety of food
      crops including corn, alfalfa, rice, and tobacco. An estimated 5 million pounds
      of carbofuran is used annually in the United States, and 45% of urban African
      American women have detectable levels of carbofuran in their plasma. Nitrosated
      carbofuran has demonstrated mutagenic properties. We examined exposure to
      carbofuran and several tumor sites among 49,877 licensed pesticide applicators
      from Iowa and North Carolina enrolled in the Agricultural Health Study. We
      obtained information regarding years of use, frequency of use in an average year,
      and when use began for 22 pesticides using self-administered questionnaires.
      Poisson regression was used to calculate rate ratios (RR) and 95% confidence
      intervals (CIs) adjusting for potential confounders. Lung cancer risk was 3-fold
      higher for those with > 109 days of lifetime exposure to carbofuran (RR = 3.05;
      95% CI, 0.94-9.87) compared with those with < 9 lifetime exposure days, with a
      significant dose-response trend for both days of use per year and total years of
      use. However, carbofuran use was not associated with lung cancer risk when
      nonexposed persons were used as the referent. In addition, carbofuran exposure
      was not associated with any other cancer site examined. Although carbamate
      pesticides are suspected human carcinogens, these results should be interpreted
      cautiously because there was no a priori hypothesis specifically linking
      carbofuran to lung cancer.

PMID- 15743717
TI  - Association of ambient air pollution with respiratory hospitalization in a
      government-designated "area of concern": the case of Windsor, Ontario.
AB  - This study is part of a larger research program to examine the relationship
      between ambient air quality and health in Windsor, Ontario, Canada. We assessed
      the association between air pollution and daily respiratory hospitalization for
      different age and sex groups from 1995 to 2000. The pollutants included were
      nitrogen dioxide, sulfur dioxide, carbon monoxide, ozone, particulate matter 10
      microm in diameter (PM10), coefficient of haze (COH), and total reduced sulfur
      (TRS). We calculated relative risk (RR) estimates using both time-series and case
      crossover methods after controlling for appropriate confounders (temperature,
      humidity, and change in barometric pressure). The results of both analyses were
      consistent. We found associations between NO2, SO2, CO, COH, or PM10 and daily
      hospital admission of respiratory diseases especially among females. For females
      0-14 years of age, there was 1-day delayed effect of NO2 (RR = 1.19, case
      crossover method), a current-day SO2 (RR = 1.11, time series), and current-day
      and 1- and 2-day delayed effects for CO by case crossover (RR = 1.15, 1.19, 1.22,
      respectively). Time-series analysis showed that 1-day delayed effect of PM10 on
      respiratory admissions of adult males (15-64 years of age), with an RR of 1.18.
      COH had significant effects on female respiratory hospitalization, especially for
      2-day delayed effects on adult females, with RRs of 1.15 and 1.29 using time
      series and case-crossover analysis, respectively. There were no significant
      associations between O3 and TRS with respiratory admissions. These findings
      provide policy makers with current risks estimates of respiratory hospitalization
      as a result of poor ambient air quality in a government designated "area of
      concern."

PMID- 15743718
TI  - Necessity to measure PCBs and organochlorine pesticide concentrations in human
      umbilical cords for fetal exposure assessment.
AB  - Three types of tissue samples--umbilical cord (UC), umbilical cord serum (CS),
      and maternal serum (MS)--have often been used to assess fetal exposure to
      chemicals. In order to know the relationship of contamination between mothers and
      fetuses, we measured persistent chemicals in comparable sets of the three tissue
      samples. Also, we analyzed the association between the chemicals in maternal and
      fetal tissues to know which tissue is the best sample for fetal exposure
      assessment. On a wet basis, the chemical concentrations were of the order MS > CS
      > UC, except for some chemicals such as cis-chlordane and endosulfan. On a lipid
      basis, the concentrations in UC were nearly equal or often higher than in MS, but
      the concentrations in CS were usually lower than in others.
      Hexachlorocyclohexanes and penta-, hexa-, and heptachlorinated biphenyls showed
      an association between the concentrations in UC versus MS, and UC versus CS.
      These chemicals also showed high correlation coefficients between the chemical
      concentrations in UC of first babies and maternal age. These chemicals were
      closely related to each other when grouped on the basis of their concentrations
      using cluster analysis. In conclusion, we insist that UC is the best sample to
      assess fetal contamination status of persistent chemicals. There is a possibility
      that the assessment based on the contamination levels in CS result in an
      underestimation.

PMID- 15743719
TI  - Effects of air pollution on heart rate variability: the VA normative aging study.
AB  - Reduced heart rate variability (HRV), a marker of poor cardiac autonomic
      function, has been associated with air pollution, especially fine particulate
      matter [< 2.5 microm in aerodynamic diameter (PM2.5)]. We examined the
      relationship between HRV [standard deviation of normal-to-normal intervals
      (SDNN), power in high frequency (HF) and low frequency (LF), and LF:HF ratio] and
      ambient air pollutants in 497 men from the Normative Aging Study in greater
      Boston, Massachusetts, seen between November 2000 and October 2003. We examined 4
      hr, 24-hr, and 48-hr moving averages of air pollution (PM2.5, particle number
      concentration, black carbon, ozone, nitrogen dioxide, sulfur dioxide, carbon
      monoxide). Controlling for potential confounders, HF decreased 20.8% [95%
      confidence interval (CI), 4.6-34.2%] and LF:HF ratio increased 18.6% (95% CI, 4.1
      35.2%) per SD (8 microg/m3) increase in 48-hr PM2.5. LF was reduced by 11.5% (95%
      CI, 0.4-21.3%) per SD (13 ppb) increment in 4-hr O3. The associations between HRV
      and PM2.5 and O3 were stronger in people with ischemic heart disease (IHD) and
      hypertension. The associations observed between SDNN and LF and PM2.5 were
      stronger in people with diabetes. People using calcium-channel blockers and beta
      blockers had lower associations between O3 and PM2.5 with LF. No effect
      modification by other cardiac medications was found. Exposures to PM2.5 and O3
      are associated with decreased HRV, and history of IHD, hypertension, and diabetes
      may confer susceptibility to autonomic dysfunction by air pollution.

PMID- 15743720
TI  - The role of syntrophic associations in sustaining anaerobic mineralization of
      chlorinated organic compounds.
AB  - Stable associations of syntrophic fermentative organisms and populations that
      consume fermentation products play key roles in the anaerobic biodegradation of
      chlorinated organic contaminants. The involvement of these syntrophic populations
      is essential for mineralization of chlorinated aromatic compounds under
      methanogenic conditions. The fermentative production of low levels of hydrogen
      (H2) can also be used to selectively deliver a limiting electron donor to
      dehalogenating organisms and achieve complete dehalogenation of chlorinated
      aliphatic contaminants such as tetrachloroethene. Thus, tracking the abundance of
      syntrophically coupled populations should aid in the development and monitoring
      of sustainable bioremediation strategies. In this study, two complementary
      nucleic acid-based methods were used to identify and assess relative changes or
      differences in the abundance of potentially important populations in complex
      anaerobic microbial communities that mineralized chlorinated aromatic compounds.
      Population dynamics were related to the consumption and production of key
      metabolic substrates, intermediates, and products. Syntrophus-like populations
      were detected in 3-chlorobenzoate-degrading communities derived from sediment or
      sludge digesters. In the presence of H2-consuming populations, characterized
      Syntrophus species ferment benzoate, a central intermediate in the anaerobic
      metabolism of 3-chlorobenzoate and 2-chlorophenol. A DNA probe that targeted
      characterized Syntrophus species was developed and used to quantify rRNA
      extracted from the 3-chlorobenzoate- and 2-chlorophenol-degrading communities.
      The level of rRNA targeted by the Syntrophus-specific probe tracked with the
      formation of benzoate during metabolism of the parent compounds. Hybridizations
      with an Archaea-specific probe and/or measurement of methane production
      demonstrated that methanogens directly benefited from the influx of benzoate
      derived electron donors, and the activities of Syntrophus-like and methanogenic
      populations in the contaminant-degrading communities were closely linked.

PMID- 15743721
TI  - Comparison of biostimulation versus bioaugmentation with bacterial strain PM1 for
      treatment of groundwater contaminated with methyl tertiary butyl ether (MTBE).
AB  - Widespread contamination of groundwater by methyl tertiary butyl ether (MTBE) has
      triggered the exploration of different technologies for in situ removal of the
      pollutant, including biostimulation of naturally occurring microbial communities
      or bioaugmentation with specific microbial strains known to biodegrade the
      oxygenate. After laboratory studies revealed that bacterial strain PM1 rapidly
      and completely biodegraded MTBE in groundwater sediments, the organism was tested
      in an in situ field study at Port Hueneme Naval Construction Battalion Center in
      Oxnard, California. Two pilot test plots (A and B) in groundwater located down
      gradient from an MTBE source were intermittently sparged with pure oxygen. Plot B
      was also inoculated with strain PM1. MTBE concentrations up-gradient from plots A
      and B initially varied temporally from 1.5 to 6 mg MTBE/L. Six months after
      treatment began, MTBE concentrations in monitoring wells down-gradient from the
      injection bed decreased substantially in the shallow zone of the groundwater in
      plots A and B, thus even in the absence of the inoculated strain PM1. In the
      deeper zone, downstream MTBE concentrations also decreased in plot A and to a
      lesser extent in plot B. Difficulties in delivery of oxygen to the deeper zone of
      plot B, evidenced by low dissolved oxygen concentrations, were likely responsible
      for low rates of MTBE removal at that location. We measured the survival and
      movement of strain PM1 in groundwater samples using two methods for detection of
      DNA sequences specific to strain PM1: TaqMan quantitative polymerase chain
      reaction, and internal transcribed spacer region analysis. A naturally occurring
      bacterial strain with > 99% 16S rDNA sequence similarity to strain PM1 was
      detected in groundwater collected at various locations at Port Hueneme, including
      outside the plots where the organism was inoculated. Addition of oxygen to
      naturally occurring microbial populations was sufficient to stimulate MTBE
      removal at this site. In some cases, however, inoculation with an MTBE-degrading
      culture may be warranted.

PMID- 15743722
TI  - Acceleration of autoimmunity by organochlorine pesticides in (NZB x NZW)F1 mice.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects women
      more frequently than men. In the (NZB times NZW)F1 mouse, a murine SLE model, the
      presence or absence of estrogen markedly influences the rate of progression of
      disease. Three organochlorine pesticides with estrogenic effects were
      administered chronically to ovariectomized female (NZB times NZW)F1 mice, and we
      measured the time to development of renal disease, the principal clinical
      manifestation of lupus in this model. Treatment with chlordecone, methoxychlor,
      or o,p -dichlorodiphenyltrichloroethane (o,p -DDT) significantly decreased the
      time to onset of renal impairment, as did treatment with 17ss-estradiol used as a
      positive control. In an expanded study of chlordecone, we found a dose-related
      early appearance of elevated anti-double-strand DNA autoantibody titers that
      corresponded with subsequent development of glomerulonephritis.
      Immunohistofluorescence confirmed early deposition of immune complexes in kidneys
      of mice treated with chlordecone. These observations are consistent with an
      effect of these organochlorine pesticides to accelerate the natural course of SLE
      in the (NZB times NZW)F1 mouse. Although we originally hypothesized that the
      effect on progression of autoimmunity was due to estrogenic properties of the
      pesticides, autoimmune effects and estrogenicity, assessed through measurement of
      uterine hypertrophy, were not well correlated. This may indicate that uterine
      hypertrophy is a poor indicator of comparative estrogenic effects of
      organochlorine pesticides on the immune system, or that the pesticides are
      influencing autoimmunity through a mode of action unrelated to their
      estrogenicity.

PMID- 15743724
TI  - Summary of a workshop on the development of health models and scenarios:
      strategies for the future.
AB  - A workshop was convened in July 2003 by the Global Change Research Program,
      Office of Research and Development at the U.S. Environmental Protection Agency,
      to review current strategies for developing human health models and scenarios in
      the context of global environmental change, particularly global climate change,
      and to outline a research agenda that effectively characterizes the interplay of
      global change with the health of human populations. The research agenda developed
      at the workshop focused on three issues: a) the development of health models, b)
      the development of health scenarios, and c) the use of health models and health
      scenarios to inform policy. The agenda identified research gaps as well as
      barriers to the development and use of models and scenarios. This report
      summarizes the workshop findings.

PMID- 15743723
TI  - Assessment of estrogenic endocrine-disrupting chemical actions in the brain using
      in vivo somatic gene transfer.
AB  - Estrogenic endocrine-disrupting chemicals abnormally stimulate vitellogenin gene
      expression and production in the liver of many male aquatic vertebrates. However,
      very few studies demonstrate the effects of estrogenic pollutants on brain
      function. We have used polyethylenimine-mediated in vivo somatic gene transfer to
      introduce an estrogen response element-thymidine kinase-luciferase (ERE-TK-LUC)
      construct into the brain. To determine if waterborne estrogenic chemicals
      modulate gene transcription in the brain, we injected the estrogen-sensitive
      construct into the brains of Nieuwkoop-Faber stage 54 Xenopus laevis tadpoles.
      Both ethinylestradiol (EE2; p < 0.002) and bisphenol A (BPA; p < 0.03) increased
      luciferase activity by 1.9- and 1.5-fold, respectively. In contrast, low
      physiologic levels of 17ss-estradiol had no effect (p > 0.05). The mixed
      antagonist/agonist tamoxifen was estrogenic in vivo and increased (p < 0.003)
      luciferase activity in the tadpole brain by 2.3-fold. There have been no previous
      reports of somatic gene transfer to the fish brain; therefore, it was necessary
      to optimize injection and transfection conditions for the adult goldfish
      (Carassius auratus). Following third brain ventricle injection of cytomegalovirus
      (CMV)-green fluorescent protein or CMV-LUC gene constructs, we established that
      cells in the telencephalon and optic tectum are transfected. Optimal
      transfections were achieved with 1 microg DNA complexed with 18 nmol 22 kDa
      polyethylenimine 4 days after brain injections. Exposure to EE2 increased brain
      luciferase activity by 2-fold in males (p < 0.05) but not in females. Activation
      of an ERE-dependent luciferase reporter gene in both tadpole and fish indicates
      that waterborne estrogens can directly modulate transcription of estrogen
      responsive genes in the brain. We provide a method adaptable to aquatic organisms
      to study the direct regulation of estrogen-responsive genes in vivo.

PMID- 15743725
TI  - Vascular dysfunction in patients with chronic arsenosis can be reversed by
      reduction of arsenic exposure.
AB  - Chronic arsenic exposure causes vascular diseases associated with systematic
      dysfunction of endogenous nitric oxide. Replacement of heavily arsenic
      contaminated drinking water with low-arsenic water is a potential intervention
      strategy for arsenosis, although the reversibility of arsenic intoxication has
      not established. In the present study, we examined urinary excretion of cyclic
      guanosine 3 ,5 -monophosphate (cGMP), a second messenger of the vasoactive
      effects of nitric oxide, and signs and symptoms for peripheral vascular function
      in 54 arsenosis patients before and after they were supplied with low-arsenic
      drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia,
      China. The arsenosis patients showed a marked decrease in urinary excretion of
      cGMP (mean +/- SEM: male, 37.0 +/- 6.1; female, 37.2 +/- 5.4 nmol/mmol
      creatinine), and a 13-month period of consuming low-arsenic drinking water
      reversed this trend (male, 68.0 +/- 5.6; female, 70.6 +/- 3.0 nmol/mmol
      creatinine) and improved peripheral vascular response to cold stress. Our
      intervention study indicates that peripheral vascular disease in arsenosis
      patients can be reversed by exposure cessation and has important implications for
      the public health approach to arsenic exposure.

PMID- 15743726
TI  - Children's exposure to volatile organic compounds as determined by longitudinal
      measurements in blood.
AB  - Blood concentrations of 11 volatile organic compounds (VOCs) were measured up to
      four times over 2 years in a probability sample of more than 150 children from
      two poor, minority neighborhoods in Minneapolis, Minnesota. Blood levels of
      benzene, carbon tetrachloride, trichloroethene, and m-/p-xylene were comparable
      with those measured in selected adults from the Third National Health and
      Nutrition Examination Survey (NHANES III), whereas concentrations of
      ethylbenzene, tetrachloroethylene, toluene, 1,1,1-trichloroethane, and o-xylene
      were two or more times lower in the children. Blood levels of styrene were more
      than twice as high, and for about 10% of the children 1,4-dichlorobenzene levels
      were greater than or equal to 10 times higher compared with NHANES III subjects.
      We observed strong statistical associations between numerous pairwise
      combinations of individual VOCs in blood (e.g., benzene and m-/p-xylene, m-/p
      xylene and o-xylene, 1,1,1-trichloroethane and m-/p-xylene, and 1,1,1
      trichloroethane and trichloroethene). Between-child variability was higher than
      within-child variability for 1,4-dichlorobenzene and tetrachloroethylene. Between
      and within-child variability were approximately the same for ethylbenzene and
      1,1,1-trichloroethane, and between-child was lower than within-child variability
      for the other seven compounds. Two-day, integrated personal air measurements
      explained almost 79% of the variance in blood levels for 1,4-dichlorobenzene and
      approximately 20% for tetrachloroethylene, toluene, m-/p-xylene, and o-xylene.
      Personal air measurements explained much less of the variance (between 0.5 and
      8%) for trichloroethene, styrene, benzene, and ethylbenzene. We observed no
      significant statistical associations between total urinary cotinine (a biomarker
      for exposure to environmental tobacco smoke) and blood VOC concentrations. For
      siblings living in the same household, we found strong statistical associations
      between measured blood VOC concentrations.

PMID- 15743727
TI  - Asthma and farm exposures in a cohort of rural Iowa children.
AB  - Epidemiologic studies of farm children are of international interest because farm
      children are less often atopic, have less allergic disease, and often have less
      asthma than do nonfarm children--findings consistent with the hygiene hypothesis.
      We studied a cohort of rural Iowa children to determine the association between
      farm and other environmental risk factors with four asthma outcomes: doctor
      diagnosed asthma, doctor-diagnosed asthma/medication for wheeze, current wheeze,
      and cough with exercise. Doctor-diagnosed asthma prevalence was 12%, but at least
      one of these four health outcomes was found in more than a third of the cohort.
      Multivariable models of the four health outcomes found independent associations
      between male sex (three asthma outcomes), age (three asthma outcomes), a personal
      history of allergies (four asthma outcomes), family history of allergic disease
      (two asthma outcomes), premature birth (one asthma outcome), early respiratory
      infection (three asthma outcomes), high-risk birth (two asthma outcomes), and
      farm exposure to raising swine and adding antibiotics to feed (two asthma
      outcomes). The high prevalence of rural childhood asthma and asthma symptoms
      underscores the need for asthma screening programs and improved asthma diagnosis
      and treatment. The high prevalence of asthma health outcomes among farm children
      living on farms that raise swine (44.1%, p = 0.01) and raise swine and add
      antibiotics to feed (55.8%, p = 0.013), despite lower rates of atopy and personal
      histories of allergy, suggests the need for awareness and prevention measures and
      more population-based studies to further assess environmental and genetic
      determinants of asthma among farm children.

PMID- 15743728
TI  - Home dampness and molds, parental atopy, and asthma in childhood: a six-year
      population-based cohort study.
AB  - Previous studies of how parental atopy and exposure to dampness and molds
      contribute to the risk of asthma have been mainly cross-sectional or prevalent
      case-control studies, where selection and information bias and temporality
      constitute problems. We assessed longitudinally the independent and joint effects
      of parental atopy and exposure to molds in dwellings on the development of asthma
      in childhood. We conducted a population-based, 6-year prospective cohort study of
      1,984 children 1-7 years of age at the baseline in 1991 (follow-up rate, 77%).
      The study population included 1,916 children without asthma at baseline and
      complete outcome information. The data collection included a baseline and follow
      up survey. The outcome of interest was development of asthma during the study
      period. The studied determinants were parental allergic diseases and four
      indicators of exposure at baseline: histories of water damage, presence of
      moisture and visible molds, and perceived mold odor in the home. A total of 138
      (7.2%) children developed asthma during the study period, resulting in an
      incidence rate of 125 cases per 10,000 person-years [95% confidence interval
      (CI), 104-146]. In Poisson regression adjusting for confounding, parental atopy
      [adjusted incidence rate ratio (IRR) 1.52; 95% CI, 1.08-2.13] and the presence of
      mold odor in the home reported at baseline (adjusted IRR 2.44; 95% CI, 1.07-5.60)
      were independent determinants of asthma incidence, but no apparent interaction
      was observed. The results of this cohort study with assessment of exposure before
      the onset of asthma strengthen the evidence on the independent effects of
      parental atopy and exposure to molds on the development of asthma.

PMID- 15743730
TI  - Cardiovascular reactivity in a simulated job interview: the role of gender role
      self-concept.
AB  - This study investigated the relation of gender role self-concept (G-SC) to
      cardiovascular and emotional reactions to an ecologically relevant stressor in a
      sample of graduating male and female university students. Thirty-seven men and 37
      women completed the Personal Attribute Questionnaire and worked on four tasks
      designed to reflect common features of a job interview. Blood pressure and heart
      rate were measured at baseline, during, and after each task; subjective stress
      was measured at baseline and after each task. Subjective and objective stress
      scores were averaged across tasks and analyzed by sex and G-SC (i.e.,
      instrumentality, expressiveness). Results indicated that women as a group
      demonstrated greater emotional reactivity, but did not differ in their
      physiological reactions when compared to men. Regardless of sex, participants'
      instrumentality scores contributed significantly to the variation in subjective
      stress response: those scoring high on instrumentality reported less stress, but
      evidenced greater blood pressure reactivity than those scoring low on
      instrumentality. These results suggest that gender roles, particularly an
      instrumental self-concept, may play an important role in both subjective and
      objective reactions to an ecologically relevant stressor.

PMID- 15743729
TI  - Racial differences in exposure to environmental tobacco smoke among children.
AB  - Exposure to environmental tobacco smoke (ETS) is a major cause of morbidity and
      mortality among U.S. children. Despite African-American children's having a lower
      reported exposure to tobacco compared to whites, they suffer disproportionately
      from tobacco-related illnesses and have higher levels of serum cotinine than
      white children. The goal of this study was to test whether African-American
      children have higher levels of serum and hair cotinine, after accounting for ETS
      exposure and various housing characteristics. We investigated the level of
      cotinine in both hair and serum in a sample of 222 children with asthma. Using a
      previously validated survey for adult smokers, we assessed each child's exposure
      to ETS. We collected detailed information on the primary residence, including
      home volume, ventilation, and overall home configuration. Despite a lower
      reported ETS exposure, African-American children had higher mean levels of serum
      cotinine (1.41 ng/mL vs. 0.97 ng/mL; p = 0.03) and hair cotinine (0.25 ng/mg vs.
      0.07 ng/mg; p < 0.001) compared with white children. After adjusting for ETS
      exposure, housing size, and other demographic characteristics, serum and hair
      cotinine levels remained significantly higher in African-American children (ss =
      0.34, p = 0.03) than in white children (ss = 1.06, p < 0.001). Housing volume was
      significantly associated with both serum and hair cotinine but did not fully
      explain the race difference. Our results demonstrate that, despite a lower
      reported exposure to ETS, African-American children with asthma had significantly
      higher levels of both serum and hair cotinine than did white children.
      Identifying causes and consequences of increased cotinine may help explain the
      striking differences in tobacco-related illnesses.

PMID- 15743731
TI  - Fatigue and job stress as predictors for sickness absence during common
      infections.
AB  - The objective of this study was to investigate the effect of health and work
      related factors as predictors of subsequent sickness absence when experiencing
      common infections (common cold, flu-like illness, and gastroenteritis). Self
      administered questionnaire data were used (baseline n = 12,140). To perform the
      analysis, employees reporting common infections in the final questionnaire were
      selected. Employees reporting sickness absence due to common infections were
      compared with a group who stayed at work during an infection. Multivariate
      survival analysis revealed no significant effects of job demands, decision
      latitude, or job strain on absence in workers experiencing common infections. Low
      levels of commitment (risk [RR] 1.22; confidence interval [CI] 1.03-1.44) and low
      job satisfaction (RR 1.36; CI 1.13-1.164) increased the chance of being absent
      during a common cold. Also, having a long-standing disease (RR 1.22; CI 1.05
      1.41) and fatigue (RR 1.20; CI 1.05-1.37) increased the chance of being absent
      during a common infection. Having an executive function decreased the chance of
      being absent. We conclude that absence during a common cold is partly influenced
      by motivational factors in work, in contrast to more severe common infections
      which are more health related. Insight in factors related to absenteeism are
      important as a start for preventive measures to reduce sickness absence.

PMID- 15743732
TI  - Heart disease attributions: introduction to the miniseries.

PMID- 15743733
TI  - Effects of anxiety and depression on heart disease attributions.
AB  - Cardiac patients' beliefs about the causes of their illness may influence their
      receptivity to psychosocial interventions. The purpose of this study was to
      determine whether depression or anxiety influence patients' attributions about
      the causes of their heart disease. The primary hypothesis was that depressed or
      anxious patients are more likely to endorse negative emotions as among the causes
      of their heart disease than are patients who are not depressed or anxious. Sixty
      nine patients with documented ischemic heart disease recruited from an exercise
      stress testing laboratory completed the Beck Depression and Anxiety Inventories
      and a heart disease attribution checklist. Univariate analyses confirmed that
      patients who are depressed or anxious are more likely than other patients to
      endorse negative emotions as causes of their heart disease. Anxiety but not
      depression was retained as an independent predictor of negative emotion
      attributions in a logistic regression analysis. We conclude that mood state
      influences cardiac patients' beliefs about the causes of their heart disease.

PMID- 15743734
TI  - Symptom experiences, symptom attributions, and causal attributions in patients
      following first-time myocardial infarction.
AB  - We examined symptom experiences, symptom attributions, and causal attributions
      reported by patients hospitalized for a first-time myocardial infarction (MI). We
      also explored the roles of symptoms, negative affect, and risk factors in
      promoting stress and other causal attributions. Patients (N = 65) completed
      measures of symptom experiences and attributions, perceived causes of their MI,
      state and trait negative affect, and risk factors. Patients attributed most of
      their symptoms to the heart condition, although rates varied from 48% (headaches)
      to 97% (nausea). The most common causal attribution was stress, followed by high
      cholesterol, heredity, fat consumption, and hypertension. Stress attributions
      were positively associated with state anxiety and specific, stress-related
      symptoms (e.g., fatigue and breathlessness). Anxious mood and stress-related
      symptoms appear to enhance the plausibility of stress as a cause of MI. Risk
      factors were moderately correlated with associated causal attributions. For many
      patients, however, attributions to hypertension, cholesterol, and family history
      of heart disease were discordant with their clinical data. Causal attributions
      remained stable over the subsequent 6 months.

PMID- 15743735
TI  - Gender differences in patients' attributions for myocardial infarction:
      implications for adaptive health behaviors.
AB  - Attributions for myocardial infarction were studied in a patient sample (N =
      157). Men and women were comparable at intake on age, health status, and
      lifestyle factors. Attributions to diet, chi2 (1, N = 157) = 8.83, p = .003, and
      exercise, chi2 (1, N = 157) = 6.60, p = .01, were less common among women than
      men. After 3 months (n = 136), women were less likely than men to report
      improving their diets or increasing exercise. Initial attributions predicted
      subsequent reports of behavior change in relevant domains. These findings suggest
      that gender differences in causal attributions for myocardial infarction may
      contribute to subsequent differences between men and women in health-related
      behavior change.

PMID- 15743736
TI  - Reflex high-risk human papillomavirus testing for women with atypical squamous
      cells of undetermined significance in cytologic smears: effects since
      implementation in a large clinical practice.
AB  - Reflex high-risk human papillomavirus (HPV) testing often is used in the
      management of women with atypical squamous cells of undetermined significance
      identified in cervicovaginal screening. Following implementation of reflex
      testing, our laboratory processed 8,022 specimens during a 20-month period;
      sufficient material was available for testing in 7,334 specimens. High-risk HPV
      was detected in 34.10% of these specimens. Detection rates varied with age, with
      positive rates as high as 58.46% in women 20 years old or younger, decreasing to
      14.58% in women older than 35 years. The detection rate, categorized in 5-year
      age increments, showed a significant decrease until after 35 years, when the rate
      remained fairly constant (P < .0001). The detection rate decreased over the time
      of the study. These results demonstrate that high-risk HPV detection might vary
      according to the age mix of the population tested and the interval after
      implementation of testing.

PMID- 15743737
TI  - Correlation of HER-2 status with estrogen and progesterone receptors and
      histologic features in 3,655 invasive breast carcinomas.
AB  - We studied the inverse relationship between HER-2 and estrogen (ER) and
      progesterone (PR) receptors using HER-2 testing and correlated HER-2 status with
      histologic features in 3,655 unselected invasive breast carcinomas.
      Immunohistochemical analysis for ER, PR, and HER-2 and fluorescence in situ
      hybridization for HER-2 were performed. ER and PR expression were decreased
      significantly in HER-2+ tumors compared with HER-2- tumors (ER, 49.1% vs 78.17%;
      PR, 24.3% vs 53.13%). Even among HER-2+ tumors, the rate of ER or PR expression
      in high-grade tumors was significantly decreased compared with intermediate-grade
      tumors. HER-2 was positive in 10.87% of grade 2 and 27.84% of grade 3 ductal
      carcinomas and negative in all grade 1 ductal carcinomas. HER-2 overexpression or
      amplification essentially was limited to grades 2 and 3 ductal carcinomas and
      correlated inversely with ER or PR expression. Although ER or PR expression is
      decreased in HER-2+ tumors, a substantial proportion of them still express ER or
      PR.

PMID- 15743738
TI  - Primary Sezary syndrome commonly shows low-grade cytologic atypia and an absence
      of epidermotropism.
AB  - The dermatopathologic findings in cases of Sezary syndrome (SS) that arise in
      patients without a previous diagnosis of mycosis fungoides have not been well
      characterized. We evaluated the histologic findings in skin biopsy specimens from
      31 patients with such primary SS and correlated them with clinical and
      hematologic parameters at the time of biopsy. The most characteristic histologic
      finding was the presence of a dermal perivascular lymphoid infiltrate, usually
      with mild to moderate cytologic atypia and variable numbers of eosinophils;
      epidermotropism was absent or minimal in 19 cases (61%). Reactive epidermal
      changes such as spongiosis, parakeratosis, and acanthosis also were present
      frequently (27 [87%], 17 [55%], 19 [61%] cases, respectively). The number of
      eosinophils present in skin biopsy specimens correlated with the level of
      peripheral blood lymphocytosis. In erythrodermic patients or patients with
      persistent xerosis and pruritus, it is important to carefully evaluate the degree
      of lymphocyte atypia in the dermal perivascular infiltrate and correlate with
      blood flow cytometric findings to diagnose primary SS. Many cases will lack the
      epidermotropism usually seen in mycosis fungoides.

PMID- 15743739
TI  - First reported cases of intravascular large cell lymphoma of the NK cell type:
      clinical, histologic, immunophenotypic, and molecular features.
AB  - Most cases of intravascular large cell lymphoma are of B-cell phenotype, with a
      few cases of T-cell lineage and rare cases with histiocytic features described. A
      definitive natural killer (NK) cell variant has not been recognized. This report
      is the first to describe the clinical, histologic, immunophenotypic, and
      molecular features of 2 cases of intravascular lymphoma with an NK cell phenotype
      (CD3epsilon+, CD2+, CD7+, CD56+, T-cell intracytoplasmic antigen-1+, perforin+,
      granzyme B+, CD20-, CD4-, CD5-, CD8-, T-cell receptor [TCR]betaF1-). Molecular
      studies for TCR gene rearrangements revealed a germline configuration. A 41-year
      old man had erythematous plaque-like subcutaneous lesions of the lower
      extremities in which biopsy revealed Epstein-Barr virus-positive intravascular
      lymphoma. Following chemotherapy and stem cell transplantation, he was alive with
      no evidence of disease at 1 year. A 47-year-old woman had myalgias, arthralgias,
      weakness, fever, altered mental status, and pancytopenia. Bone marrow biopsy
      demonstrated intravascular lymphoma. Therapy was initiated; however, her
      condition deteriorated rapidly, and she died. Autopsy revealed involvement of
      multiple organs, including brain, kidneys, ovaries, and bone marrow. These cases
      represent the first documented examples of an NK cell variant of intravascular
      lymphoma.

PMID- 15743740
TI  - Phyllodes tumors of the breast: the role of pathologic parameters.
AB  - We aimed to establish whether morphologic parameters were prognostically
      important in a large series of breast phyllodes tumors in Asian women. Of 335
      phyllodes tumors diagnosed at the Department of Pathology, Singapore General
      Hospital, Singapore, between January 1992 and December 2002, 250 (74.6%) were
      benign, 54 (16.1%) borderline, and 31 (9.3%) malignant, based on histologic
      review of archival slides. Of the women, 43 (12.8%) experienced recurrences
      during the follow-up period. Recurrent disease was correlated with grade or
      classification (P = .028), stromal atypia (P = .016), stromal hypercellularity (P
      = .046), and permeative microscopic borders (P = .021). Multivariate analysis
      revealed that independent predictors of recurrence were pseudoangiomatous stromal
      hyperplasia (PASH) and margin status, whereby the presence of PASH and complete
      or negative margins reduced recurrence hazards by 51.3% and 51.7% respectively.
      The 7 women who died of disease during follow-up had malignant phyllodes tumor at
      the outset and experienced recurrences, and death was preceded by distant
      metastases.

PMID- 15743741
TI  - Immunohistochemical analysis in steatohepatitis: does it have a role in diagnosis
      and management?

PMID- 15743742
TI  - Reporting endometrial cells in women 40 years and older: assessing the clinical
      usefulness of Bethesda 2001.
AB  - We assessed the usefulness of revised Bethesda System reporting of exfoliated
      benign endometrial cells (EMs) in postmenopausal women. Cervicovaginal cytology
      specimens with benign EMs in postmenopausal women and "out-of-phase EMs" in
      premenopausal women 40 years and older were identified. Cases with histologic
      follow-up within 12 months were selected. There was tissue follow-up for 130
      postmenopausal women: 10 (7.7%) had significant findings (endometrial
      adenocarcinoma, 6 [2 (33%) in asymptomatic women]; complex atypical endometrial
      hyperplasia [CAH], 3; leiomyosarcoma, 1); 20 were receiving hormone replacement
      therapy (HRT; n = 15) or tamoxifen (n = 5); 2 (10%) had significant pathology
      (endometrial adenocarcinoma, 1; CAH, 1). Eight not taking hormones (7.3%) had
      significant pathology (adenocarcinoma, 5; CAH, 2; leiomyosarcoma, 1). There were
      follow-up data for 96 premenopausal women; only 1 (who had vaginal bleeding) had
      significant pathology (CAH). The difference in incidence of preneoplastic and
      neoplastic conditions after a cytologic interpretation of "benign EM" between
      postmenopausal and premenopausal women was significant (P pound .025); There was
      no difference between postmenopausal women receiving or not receiving HRT (P >
      .05). Reporting benign EMs for premenopausal women 40 years and older has no
      clinical significance but does for postmenopausal women, regardless of HRT and
      symptoms.

PMID- 15743743
TI  - Comparison of sample preservation methods for clinical trace element analysis by
      inductively coupled plasma mass spectrometry.
AB  - The effects of chemical additives and storage temperatures on measurement of 16
      trace elements in urine by inductively coupled plasma mass spectrometry (ICP-MS)
      were evaluated. A 24-hour urine specimen was supplemented with concentrations of
      the elements. Aliquots containing 1 of 4 chemical additives were stored at 3
      different temperatures in sealed polypropylene containers. Elemental
      concentrations were determined by ICP-MS for the resulting samples after 1, 2, 8,
      and 65 days of storage. Initial element concentrations measured within 8 hours of
      specimen preparation were consistent with expected concentrations (except for
      aluminum). For most elements, preservation and storage conditions yielded
      consistent measured concentrations throughout the experiment. Notable exceptions
      were for aluminum (general rise over time) and mercury (general decrease over
      time). Adding boric acid and potassium pyrosulfate resulted in sample
      contamination; elemental contamination was concentration-dependent for both.
      Although little microbial contamination was observed during the experiment,
      refrigeration of samples is recommended to curtail bacterial growth in nonsterile
      specimens. In light of these results, refrigerated urine storage without the use
      of chemical additives is an effective preservation method for ICP-MS analysis of
      many trace elements.

PMID- 15743744
TI  - Role of bax mutations in apoptosis in colorectal cancers with microsatellite
      instability.
AB  - Half of colorectal tumors with microsatellite instability contain frameshift
      mutations in the (G)8 tract of bax, a major apoptosis effector, but their
      functional significance remains unclear. We studied the role of bax mutations on
      bax expression and apoptosis in 59 primary colorectal cancers of which 41 were
      microsatellite unstable. Tumors were screened for bax(G)8 mutations and evaluated
      immunohistochemically for bax, bcl-2, and p53 protein expression and apoptotic
      (M30 cytoDEATH) and proliferative (Ki-67) indexes. We identified bax(G)8
      mutations in 20 (49%) of 41 unstable tumors; the mutations were associated
      significantly with proximal, poorly differentiated, or mucinous adenocarcinomas.
      Most bax-mutated cases displayed a bax-immunonegative zone in all or part of the
      tumor that was proved to correspond to biallelic bax(G)8 mutations by
      microdissection and to confer growth advantage to the tumor by decreasing
      apoptosis compared with adjacent bax-immunopositive tumor. Biallelic bax(G)8
      mutations are subject to positive selection pressure and might disable apoptosis
      in colorectal cancer.

PMID- 15743745
TI  - Postsplenectomy cytomegaloviral mononucleosis: marked lymphocytosis, TCRgamma
      gene rearrangements, and impaired IgM response.
AB  - People who have undergone splenectomy mount a poor IgM response to bacterial
      polysaccharide vaccines. Whether this defect is true during natural bacterial and
      viral infections is unknown. We present 2 cases of postsplenectomy
      cytomegalovirus (CMV)-induced mononucleosis with impaired IgM but normal to
      augmented IgG response. The cases presented initial diagnostic challenges owing
      to a prolonged course of infection, marked lymphocytosis (peak lymphocyte count,
      27,900/microL [27.9 10(9)/L]), clonal T-cell proliferation with T-cell receptor g
      gene rearrangements, and remote history of splenectomy. However, the acute nature
      of the infections, serial determinations of the anti-CMV IgM and IgG, exclusion
      of other causes, and detection of CMV in the blood established the diagnosis and
      revealed the deranged antibody response. The infections resolved without specific
      treatment. These cases suggest that the spleen might be a primary site for
      specific anti-CMV IgM response.

PMID- 15743746
TI  - Altered expression of alpha-methylacyl-coenzyme A racemase in prostatic
      adenocarcinoma following hormone therapy.
AB  - alpha-Methylacyl-coenzyme A racemase (AMACR) is a sensitive and specific tissue
      marker for the diagnosis of prostatic carcinoma. However, limited data are
      available on AMACR expression in residual prostatic carcinoma following hormone
      therapy. We analyzed 64 residual or recurrent prostatic adenocarcinomas following
      hormonal therapy for the expression of AMACR using a monoclonal antibody (P504S)
      to AMACR. In 20 localized cases, AMACR staining was absent in 11 (55%), 1+ in 6
      (30%), and 2+ or 3+ in 3 (15%). However, in 15 metastatic cases, AMACR was absent
      in 1 (7%), 1+ in 3 (20%), and 2+ or 3+ in 11 (73%). None of the 29
      postradiotherapy cases showed complete absence of AMACR staining: 2 (7%) were 1+,
      and 27 (93%) were 2+ or 3+. AMACR expression was reduced significantly in the
      majority of posthormonal residual carcinomas, whereas in postradiotherapy and in
      hormone-refractory metastatic prostatic adenocarcinoma, AMACR expression was
      retained. Therefore, the diagnosis of residual prostatic carcinoma after hormonal
      therapy using AMACR immunostaining must be interpreted with caution. Furthermore,
      AMACR might have a role in the recurrence of prostatic adenocarcinoma after
      medical therapy.

PMID- 15743747
TI  - Chronic lymphocytic leukemia/small lymphocytic lymphoma associated with IgM
      paraprotein.
AB  - We studied the clinicopathologic, immunophenotypic, and cytogenetic features of
      26 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma
      (CLL/SLL) associated with serum IgM paraprotein. The study group (16 men; 10
      women; median age, 64 years; range, 40-82 years) represents approximately 2.5% of
      CLL/SLL cases at our institution. The paraprotein level ranged from 1 to 14 g/L
      (median, 4 g/L). Neoplasms in bone marrow were composed of small round
      lymphocytes arranged in nodular (n = 6), diffuse (n = 5), interstitial (n = 5),
      or mixed (n = 10) patterns. All cases were positive for monotypic surface
      immunoglobulin light chain, IgM/IgD, CD5, CD19, CD20, and CD23. CD11c (14/20
      [70%]), CD79b (11/19 [58%]), FMC-7 (11/26 [42%]), CD22 (8/20 [40%]), and ZAP-70
      (6/19 [32%]) were expressed in subsets of cases. Of 17 bone marrow specimens
      assessed by conventional cytogenetics, 6 were abnormal and 11 were diploid. The
      overall survival of this group (median follow-up, 24 months) was not
      significantly different from that for an age-, sex-and stage-matched group of 52
      CLL/SLL patients without IgM paraprotein (P = .60). We conclude that CLL/SLL
      cases with serum IgM paraprotein are similar to other CLL/SLL cases in their
      clinicopathologic and immunophenotypic features.

PMID- 15743748
TI  - Analytical relationships among Biosite, Bayer, and Roche methods for BNP and NT
      proBNP.
AB  - This study determined whether, for patient monitoring, it is feasible to convert
      B-type natriuretic peptide (BNP) results obtained using Triage (BNP, Biosite, San
      Diego, CA), Centaur (BNP, Bayer Diagnostics, Tarrytown, NY), and Elecsys 2010 (N
      terminal proBNP; Roche, Indianapolis, IN) assays. Concordance between assays and
      effects of renal impairment also were assessed. Samples were primarily from
      emergency center patients. Biosite testing was performed immediately; Bayer and
      Roche testing was performed later on plasma stored frozen (-30 degrees C).
      Logistic regression relationships were as follows: Bayer = 0.57 Biosite + 23.1, n
      = 121, R2 = 0.85; Roche = 6.09 Biosite -220.4 + 1,131.6 (if female), n = 131, R2
      = 0.57; and Roche = 15.34 Bayer + 2,400.8, n = 150, R2 = 0.23. An increased serum
      creatinine level (>/=2 mg/dL [>/=177 micromol/L]) influenced the Roche results.
      We conclude the following from this preliminary study: (1) Results from one
      method cannot be converted reliably to another using regression relationships.
      (2) When using manufacturers'cutoff values, concordance between assays was
      acceptable. (3) Renal impairment affected Roche results.

PMID- 15743749
TI  - Multitarget FISH analysis in the diagnosis of lung cancer.
AB  - The aim of the present study was to explore the diagnostic usefulness of the
      multitarget fluorescence in situ hybridization (FISH) test, LAVysion (Vysis,
      Downers Grove, IL), for the detection of lung cancer cells in cytologic
      specimens. Specimens from bronchial washings, bronchial brushings, and
      transbronchial fine-needle aspirates (TBNAs) from 100 patients with suspected
      lung cancer and from a control group of 71 patients with nonneoplastic lung
      disorders were analyzed. FISH positivity was defined as more than 5 cells with
      gains of at least 2 chromosomes or gene loci. FISH significantly improved the
      sensitivity of bronchial brushings from 49% to 73%. The specificities of FISH and
      cytologic examination were 87% and 100%, respectively. In contrast, FISH provided
      no additional diagnostic information in TBNAs and bronchial washings. There was
      no increased prevalence of genetic changes in contralateral bronchial washings
      from patients with lung cancer compared with the control group. The quantity of
      previous smoking had no effect on the prevalence of chromosomal changes.

PMID- 15743751
TI  - Primary lung adenocarcinoma with massive lymphocyte infiltration.
AB  - We report 6 cases of adenocarcinoma with massive lymphocyte infiltration. This
      adenocarcinoma is found in 0.7% of surgically resected primary lung
      adenocarcinomas. The tumor was located in the peripheral portion in all cases.
      Lymph node metastasis was detected in 4 cases. The mean follow-up period was 49.8
      months; all patients were alive without recurrence despite advanced pathologic
      stage. Histologically, the tumors revealed an acinar and glandular structure, and
      the cancer epithelium was destroyed by infiltrating lymphocytes. The lung
      parenchyma was destroyed by the severe inflammatory cell infiltration without
      dense fibrosis. Immunohistochemical staining revealed that most infiltrating
      lymphocytes were positive for CD3 or CD20. None of the tumors were positive for
      latent membrane protein-1, bcl-2, or Epstein-Barr virus-encoded small RNA-1. This
      type of adenocarcinoma occurs in old age, and good outcome and distinctive
      histologic features were observed. We refer to it as primary lung adenocarcinoma
      with massive lymphocyte infiltration.

PMID- 15743752
TI  - Performance of an automated immature granulocyte count as a predictor of neonatal
      sepsis.
AB  - Neonatologists use immature granulocytes (IG) in manual differential counts as an
      indicator of sepsis. This study was designed to compare the predictive ability of
      automated vs manual IG counts for neonatal sepsis. Infants undergoing sepsis
      evaluation were identified prospectively for study if a CBC count was obtained in
      temporal proximity to the blood culture. Automated IG counts were obtained from
      the research software of the Sysmex XE-2100 (Sysmex, Kobe, Japan). Manual average
      IG counts were obtained from two 100-cell manual differential counts
      independently performed by a technologist and a hematopathology resident. A
      comparative analysis of manual and automated IG counts showed considerable
      overlap of ranges. The highest positive blood culture rate occurred in the
      nonneutropenic preterm subset of infant older than 7 days (21/55 [38%]). For
      these infants, elevated IG counts by manual and automated methods were associated
      significantly with positive blood culture results (odds ratio, manual, 3.74; odds
      ratio, automated, 3.63), albeit with low sensitivity.

PMID- 15743753
TI  - The use of protein tyrosine phosphatase 1B and insulin receptor immunostains to
      differentiate nonalcoholic from alcoholic steatohepatitis in liver biopsy
      specimens.
AB  - Nonalcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) and
      typically are indistinguishable, histologically. The diagnosis relies on
      reporting of alcohol consumption. The metabolic syndrome involving insulin
      resistance is associated with nonalcoholic fatty liver disease (NAFLD). Protein
      tyrosine phosphatase 1B (PTP1B) negatively regulates the insulin receptor (IR).
      Increased PTP1B expression is seen in obesity and possibly is responsible for the
      insulin resistance seen in the metabolic syndrome. The study objective was to
      determine whether biopsy specimens with steatohepatitis could be classified
      accurately as alcoholic or nonalcoholic by immunohistochemical stains. We
      selected 241 cases of steatohepatitis, comprising 53 and 188 cases of alcoholic
      and NAFLD, respectively. Specimens were stained with PTP1B and IR (b subunit) and
      classified as NASH or ASH. The staining pattern predicted 60 cases of ASH and 181
      cases of NASH. Results correlated with clinical diagnoses in 70% and 88% of ASH
      and NASH cases, respectively (odds ratio, 16.6; 95% confidence interval, 8.2
      35.4).

PMID- 15743754
TI  - Epstein-Barr virus.

PMID- 15743755
TI  - A prospective study of the long-term efficacy of local methyl prednisolone
      acetate injection in the management of mild carpal tunnel syndrome.
AB  - OBJECTIVE: Local glucocorticoid injections are used to treat carpal tunnel
      syndrome (CTS). However, this treatment is associated with frequent relapses. An
      important limitation of studies with higher relapse rates is that no attempt has
      been made to identify patients with mild or severe disease. We evaluated the
      efficacy of local glucocorticoid injection in patients with mild CTS. METHOD:
      Mild CTS was defined as intermittent symptoms without absence of sensations,
      muscle atrophy or weakness of the thenar muscles. Forty-eight patients with
      idiopathic mild CTS were evaluated before and 3 and 12 months after a single
      local injection of 40 mg methyl prednisolone acetate. Outcome was assessed by
      overall satisfaction on a 100 mm visual analogue scale, the Boston self
      administered questionnaire for symptom severity and functional scores and
      improvement in the electrophysiological parameters. RESULTS: At 3 months, 93.7%
      of the patients reported marked improvement in their symptoms, with significant
      improvement in the mean values of the nerve conduction parameters distal motor
      latency at the wrist (DML) (P = 0.00001), distal sensory latency at mid-palm (DSL
      MP) (P = 0.014) and distal sensory latency at the wrist (DSL W) (P = 0.0003), and
      symptom severity (P = 4.96 x 10(-8)) and the functional scores (P = 3.56 x 10(
      5)). Significant improvement was still present for DML (P = 1.39 x 10(-5)) at 12
      months. Almost 50% of the patients achieved normalization in the
      electrophysiological study. At a median follow-up of 16 months, 79% patients
      continued to have improvement in their symptoms. Eight patients (16.6%) relapsed
      following the initial response. CONCLUSIONS: Local glucocorticoid injection
      results in long-term improvement in nerve conduction parameters, symptom severity
      and functional scores in patients with mild CTS.

PMID- 15743756
TI  - Manganese superoxide dismutase protects the proliferative capacity of confluent
      normal human fibroblasts.
AB  - We tested the hypothesis that manganese superoxide dismutase (MnSOD), an
      antioxidant enzyme, regulates the proliferative potential of confluent human
      fibroblasts. Normal human skin (AG01522) and lung (WI38, CCL-75) fibroblasts kept
      in confluence (>95% G(0)/G(1)) showed a significant decrease in their capacity to
      re-enter the proliferation cycle after 40-60 days. The inhibition of re-entry was
      accompanied with the age-dependent increase of p16 protein levels in the
      confluent culture. Adenoviral mediated overexpression of MnSOD during confluent
      growth suppressed p16, enhanced p21 protein accumulation, and protected
      fibroblasts against the loss of proliferation potential. Increases in p21 protein
      levels in MnSOD overexpressing confluent fibroblasts were independent of p53
      protein levels. p53 protein levels did not change in control, replication
      defective adenovirus containing an insertless vector (AdBgl II), or AdMnSOD
      infected confluent cells cultured for 20 and 60 days. In addition, MnSOD-induced
      protection of the proliferation capacity of confluent fibroblasts was independent
      of their telomerase activity. However, telomerase-transformed fibroblasts showed
      increased MnSOD expression in confluent growth, maintaining their capacity to re
      enter the proliferation cycle. Although inactivation of the retinoblastoma
      protein in cells subcultured from the 60-day confluent control, AdBgl II-, and
      AdMnSOD-infected fibroblasts was identical, only MnSOD-overexpressing cells
      showed a higher percentage of S-phase. These results support the hypothesis that
      a redox-sensitive checkpoint regulated the progression of fibroblasts from
      G(0)/G(1) to S-phase.

PMID- 15743757
TI  - Developmental regulation of gonadotropin-releasing hormone gene expression by the
      MSX and DLX homeodomain protein families.
AB  - Gonadotropin-releasing hormone (GnRH) is the central regulator of the
      hypothalamic-pituitary-gonadal axis, controlling sexual maturation and fertility
      in diverse species from fish to humans. GnRH gene expression is limited to a
      discrete population of neurons that migrate through the nasal region into the
      hypothalamus during embryonic development. The GnRH regulatory region contains
      four conserved homeodomain binding sites (ATTA) that are essential for basal
      promoter activity and cell-specific expression of the GnRH gene. MSX and DLX are
      members of the Antennapedia class of non-Hox homeodomain transcription factors
      that regulate gene expression and influence development of the craniofacial
      structures and anterior forebrain. Here, we report that expression patterns of
      the Msx and Dlx families of homeodomain transcription factors largely coincide
      with the migratory route of GnRH neurons and co-express with GnRH in neurons
      during embryonic development. In addition, MSX and DLX family members bind
      directly to the ATTA consensus sequences and regulate transcriptional activity of
      the GnRH promoter. Finally, mice lacking MSX1 or DLX1 and 2 show altered numbers
      of GnRH-expressing cells in regions where these factors likely function. These
      findings strongly support a role for MSX and DLX in contributing to
      spatiotemporal regulation of GnRH transcription during development.

PMID- 15743759
TI  - Ceramide 1-phosphate acts as a positive allosteric activator of group IVA
      cytosolic phospholipase A2 alpha and enhances the interaction of the enzyme with
      phosphatidylcholine.
AB  - Previous findings from our laboratory have demonstrated that cPLA(2)alpha is
      directly activated by the emerging bioactive sphingolipid, ceramide 1-phosphate
      (C-1-P) (1). In this study, a Triton X-100/phosphatidylcholine (PC) mixed micelle
      assay was utilized to determine the kinetics and specificity of this lipid-enzyme
      interaction. Using this assay, the addition of C-1-P induced a dramatic increase
      in the activity of cPLA(2)alpha (>15-fold) with a K(a) of 2.4 mol % C-1-P/Triton
      X-100 micelle. This activation was highly specific as the addition of other
      lipids had insignificant effects on cPLA(2)alpha activity. Studies using surface
      dilution kinetics revealed that C-1-P had no effect on the Michaelis-Menten
      constant, K(m)(B), but decreased the dissociation constant (K (A)(s)) value by
      87%. Thus, C-1-P not only increases the membrane affinity of cPLA(2)alpha but
      also may act as an allosteric activator of the enzyme. Surface plasmon resonance
      analysis of the C-1-P/cPLA(2)alpha interaction verified a decrease in the
      dissociation constant, demonstrating that cPLA(2)alpha bound PC vesicles
      containing C-1-P with increased affinity (5-fold) compared with PC vesicles
      alone. The effect on the dissociation rate of cPLA(2)alpha was also found to be
      lipid-specific with the exception of phosphatidylinositol 4,5-bisphosphate, which
      caused a modest increase in vesicle affinity (2-fold). Lastly, the binding site
      for C-1-P was determined to be within the C2-domain of cPLA(2)alpha, unlike
      phosphatidylinositol 4,5-bisphosphate. These data demonstrate a novel interaction
      site for C-1-P and suggest that C-1-P may function to recruit cPLA(2)alpha to
      intracellular membranes as well as allosterically activate the membrane
      associated enzyme.

PMID- 15743758
TI  - Transforming growth factor (TGF)-beta-activated kinase 1 mimics and mediates TGF
      beta-induced stimulation of type II collagen synthesis in chondrocytes
      independent of Col2a1 transcription and Smad3 signaling.
AB  - Transforming growth factor (TGF)-beta, bone morphogenetic protein (BMP), and
      interleukin-1beta activate TGF-beta-activated kinase 1 (TAK1), which lies
      upstream of the p38 MAPK, JNK, and NF-kappaB pathways. Our knowledge remains
      incomplete of TAK1 target genes, requirement for cooperative signaling, and
      capacity for shared or segregated ligand-dependent responses. We show that
      adenoviral overexpression of TAK1a in articular chondrocytes stimulated type II
      collagen protein synthesis 3-6-fold and mimicked the response to TGF-beta1 and
      BMP2. Both factors activated endogenous TAK1 and its activating protein, TAB1,
      and the collagen response was inhibited by dominant-negative TAK1a. Isoform
      specific antibodies to TGF-beta blocked the response to endogenous and exogenous
      TGF-beta but not the response to TAK1a. Expression of Smad3 did not stimulate
      type II collagen synthesis or enhance that caused by TGF-beta1 or TAK1a, in
      contrast to its effects on its endogenous targets, CTGF and plasminogen-activated
      inhibitor-1. TAK1a, overexpressed alone and immunoprecipitated, phosphorylated
      MKK6 and stimulated the plasminogen-activated inhibitor-1 promoter following
      transient transfection; both effects were enhanced by TAB1 coexpression, but type
      II collagen synthesis was not. Stimulation by TAK1a or TGF-beta did not require
      increased Col2a1 mRNA, and TAK1 actually reduced Col2a1 mRNA in parallel with the
      cartilage markers, SRY-type HMG box 9 (Sox9) and aggrecan. Thus, TAK1 increased
      target gene expression (Col2a1) by translational or posttranslational mechanisms
      as a Smad3-independent response shared by TGF-beta1 and BMP2.

PMID- 15743760
TI  - Acid sphingomyelinase is indispensable for UV light-induced Bax conformational
      change at the mitochondrial membrane.
AB  - Ultraviolet light-induced apoptosis can be caused by DNA damage but also involves
      immediate-early cell death cascades characteristic of death receptor signaling.
      Here we show that the UV light-induced apoptotic signaling pathway is unique,
      targeting Bax activation at the mitochondrial membrane independent of caspase-8
      or cathepsin D activity. Cells deficient in acid sphingomyelinase (ASMase) do not
      show UV light-induced Bax activation, cytochrome c release, or apoptosis. In
      ASMase-deficient cells, the apoptotic UV light response is restored by stable or
      transient expression of human ASMase. Bax conformational change in ASMase(-/-)
      cells is also caused by synthetic C(16)-ceramide acting on intact cells or
      isolated mitochondria. The results suggest that UV light-triggered ASMase
      activation is essentially required for Bax conformational change leading to
      mitochondrial release of pro-apoptotic factors like cytochrome c and Smac.

PMID- 15743761
TI  - G alpha 12/13- and reactive oxygen species-dependent activation of c-Jun NH2
      terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor
      stimulation in rat neonatal cardiomyocytes.
AB  - In the present study, we examined signal transduction mechanism of reactive
      oxygen species (ROS) production and the role of ROS in angiotensin II-induced
      activation of mitogen-activated protein kinases (MAPKs) in rat neonatal
      cardiomyocytes. Among three MAPKs, c-Jun NH(2)-terminal kinase (JNK) and p38 MAPK
      required ROS production for activation, as an NADPH oxidase inhibitor,
      diphenyleneiodonium, inhibited the activation. The angiotensin II-induced
      activation of JNK and p38 MAPK was also inhibited by the expression of the
      Galpha(12/13)-specific regulator of G protein signaling (RGS) domain, a specific
      inhibitor of Galpha(12/13), but not by an RGS domain specific for Galpha(q).
      Constitutively active Galpha(12)- or Galpha(13)-induced activation of JNK and p38
      MAPK, but not extracellular signal-regulated kinase (ERK), was inhibited by
      diphenyleneiodonium. Angiotensin II receptor stimulation rapidly activated
      Galpha(13), which was completely inhibited by the Galpha(12/13)-specific RGS
      domain. Furthermore, the Galpha(12/13)-specific but not the Galpha(q)-specific
      RGS domain inhibited angiotensin II-induced ROS production. Dominant negative Rac
      inhibited angiotensin II-stimulated ROS production, JNK activation, and p38 MAPK
      activation but did not affect ERK activation. Rac activation was mediated by Rho
      and Rho kinase, because Rac activation was inhibited by C3 toxin and a Rho kinase
      inhibitor, Y27632. Furthermore, angiotensin II-induced Rho activation was
      inhibited by Galpha(12/13)-specific RGS domain but not dominant negative Rac. An
      inhibitor of epidermal growth factor receptor kinase AG1478 did not affect
      angiotensin II-induced JNK activation cascade. These results suggest that
      Galpha(12/13)-mediated ROS production through Rho and Rac is essential for JNK
      and p38 MAPK activation.

PMID- 15743762
TI  - c-Jun N-terminal kinase (JNK) positively regulates NFATc2 transactivation through
      phosphorylation within the N-terminal regulatory domain.
AB  - The nuclear factor of activated T cells (NFAT) family of transcription factors
      regulates the transcription of cytokine genes and other genes involved in the
      regulation and function of the immune system. NFAT activity is regulated by the
      phosphatase calcineurin, which binds and dephosphorylates the NFAT N-terminal
      regulatory domain, a critical step required for nuclear translocation and
      transcriptional activity. Here we show that the mitogen-activated protein kinase
      (MAPK) JNK activates NFATc2-dependent transcription. Mass spectrometry revealed
      that JNK phosphorylates at least six residues within the NFATc2 regulatory domain
      in vitro. Transfection of cells with a chimeric construct encoding the GAL-4 DNA
      binding domain linked to wild-type NFATc2 showed that JNK stimulates the NFATc2
      transactivation domain in activated Jurkat T lymphocytes, an effect that is
      inhibited by dominant-negative versions of JNK. Likewise, the mutation of the
      phosphorylation sites identified revealed that Thr(116) and Ser(170) are critical
      for the transactivation of NFATc2 by JNK. In addition, clustered mutation of the
      SP-conserved motifs of NFATc2 showed that SP1 and SP2, but not SP3, are also
      important for the inducible transactivation of NFATc2. Furthermore, mass
      spectrometry analysis of NFATc2-transfected cells indicated that the activation
      of the JNK pathway results in the in vivo phosphorylation of Thr(116). Our
      results indicate that, unlike other NFAT members, the transcriptional activity of
      NFATc2 is up-regulated by JNK. JNK-mediated phosphorylation of NFATs thus appears
      to play a differential physiological role among NFAT family members.

PMID- 15743763
TI  - A novel eukaryotic selenoprotein in the haptophyte alga Emiliania huxleyi.
AB  - The diversity of selenoproteins raises the question of why many life forms
      require selenium. Especially in photosynthetic organisms, the biochemical basis
      for the requirement for selenium is unclear because there is little information
      on selenoproteins. We found six selenium-containing proteins in a haptophyte
      alga, Emiliania huxleyi, which requires selenium for growth. The 27-kDa protein
      EhSEP2 was isolated, and its cDNA was cloned. The deduced amino acid sequence
      revealed that EhSEP2 is homologous to protein disulfide isomerase (PDI) and
      contains a highly conserved thioredoxin domain. The nucleotide sequence contains
      an in-frame TGA codon encoding selenocysteine at the position corresponding to
      the cysteine residue in the reaction center of known PDIs. However, no typical
      selenocysteine insertion sequence was found in the EhSEP2 cDNA. The EhSEP2 mRNA
      level was related to the abundance of selenium. E. huxleyi possesses a novel PDI
      like selenoprotein and may have a novel type of selenocysteine insertion
      machinery.

PMID- 15743764
TI  - Specific kinetic alterations of human CaV2.1 calcium channels produced by
      mutation S218L causing familial hemiplegic migraine and delayed cerebral edema
      and coma after minor head trauma.
AB  - Mutation S218L in the Ca(V)2.1 alpha(1) subunit of P/Q-type Ca(2+) channels
      produces a severe clinical phenotype in which typical attacks of familial
      hemiplegic migraine (FHM) triggered by minor head trauma are followed, after a
      lucid interval, by deep (even fatal) coma and long lasting severe cerebral edema.
      We investigated the functional consequences of this mutation on human Ca(V)2.1
      channels expressed in human embryonic kidney 293 cells and in neurons from
      Ca(V)2.1 alpha(1)(-/-) mice by combining single channel and whole cell patch
      clamp recordings. Mutation S218L produced a shift to lower voltages of the single
      channel activation curve and a consequent increase of both single channel and
      whole cell Ba(2+) influx in both neurons and human embryonic kidney 293 cells.
      Compared with the other FHM-1 mutants, the S218L shows one of the largest gains
      of function, especially for small depolarizations, which are insufficient to open
      the wild-type channel. S218L channels open at voltages close to the resting
      potential of many neurons. Moreover, the S218L mutation has unique effects on the
      kinetics of inactivation of the channel because it introduces a large component
      of current that inactivates very slowly, and it increases the rate of recovery
      from inactivation. During long depolarizations at voltages that are attained
      during cortical spreading depression, the extent of inactivation of the S218L
      channel is considerably smaller than that of the wild-type channel. We discuss
      how the unique combination of a particularly slow inactivation during cortical
      spreading depression and a particularly low threshold of channel activation might
      lead to delayed severe cerebral edema and coma after minor head trauma.

PMID- 15743765
TI  - Decreased stability and translation of T cell receptor zeta mRNA with an
      alternatively spliced 3'-untranslated region contribute to zeta chain down
      regulation in patients with systemic lupus erythematosus.
AB  - The molecular mechanisms involved in the aberrant expression of T cell receptor
      (TCR) zeta chain of patients with systemic lupus erythematosus are not known.
      Previously we demonstrated that although normal T cells express high levels of
      TCR zeta mRNA with wild-type (WT) 3' untranslated region (3' UTR), systemic lupus
      erythematosus T cells display significantly high levels of TCR zeta mRNA with the
      alternatively spliced (AS) 3' UTR form, which is derived by splice deletion of
      nucleotides 672-1233 of the TCR zeta transcript. Here we report that the
      stability of TCR zeta mRNA with an AS 3' UTR is low compared with TCR zeta mRNA
      with WT 3' UTR. AS 3' UTR, but not WT 3' UTR, conferred similar instability to
      the luciferase gene. Immunoblotting of cell lysates derived from transfected COS
      7 cells demonstrated that TCR zeta with AS 3' UTR produced low amounts of 16-kDa
      protein. In vitro transcription and translation also produced low amounts of
      protein from TCR zeta with AS 3' UTR. Taken together our findings suggest that
      nucleotides 672-1233 bp of TCR zeta 3' UTR play a critical role in its stability
      and also have elements required for the translational regulation of TCR zeta
      chain expression in human T cells.

PMID- 15743766
TI  - Disulfide linkage controls the affinity and stoichiometry of IgE Fcepsilon3-4
      binding to FcepsilonRI.
AB  - IgE antibodies cause long-term sensitization of tissue mast cells and blood
      basophils toward allergen-induced cross-linking and triggering of allergic
      inflammation. This persistence of IgE binding is due to its uniquely high
      affinity for the receptor FcepsilonRI and in particular its slow rate of
      dissociation once bound. The binding interface consists of two subsites, one
      contributed by each Cepsilon3 domain of IgE Fc in a 1:1 complex. We have
      investigated the contributions of Cepsilon3 disulfide linkage and glycosylation
      to the kinetics and affinity of binding of an Fc subfragment (Fcepsilon3-4) to a
      soluble receptor fragment (sFcepsilonRIalpha). In contrast to IgG Fc where
      deglycosylation abrogates receptor binding activity, the removal of the N-linked
      carbohydrate at Asn-394 in Fcepsilon3-4 only reduces binding affinity by a factor
      of 4, principally because of a faster off-rate. Removal of the inter-heavy chain
      disulfide bond unexpectedly resulted in a fragment with a much faster off-rate
      and the potential to form a complex with a 2:1 stoichiometry
      (sFcepsilonRIalpha:Fcepsilon3-4). This permitted the determination of the
      affinity of a single, natively folded Cepsilon3 domain for the first time. The
      low affinity Ka approximately 10(5)-10(6) m-1, similar to that determined
      previously for an isolated and partially folded Cepsilon3 domain, demonstrates
      that substantial reduction in affinity can be achieved by preventing the
      engagement of one of the two Cepsilon3 domains. Recent structural data indicate
      that conformational change in IgE is required to allow both Cepsilon3 domains to
      bind, and thus an allosteric inhibitor that prevents access to the second
      Cepsilon3 has the potential to reduce the ability of IgE to sensitize allergic
      effector cells.

PMID- 15743767
TI  - Growth hormone receptor is a target for presenilin-dependent gamma-secretase
      cleavage.
AB  - Growth hormone receptor (GHR) is a cytokine receptor superfamily member that
      binds growth hormone (GH) via its extracellular domain and signals via
      interaction of its cytoplasmic domain with JAK2 and other signaling molecules.
      GHR is a target for inducible metalloprotease-mediated cleavage in its
      perimembranous extracellular domain, a process that liberates the extracellular
      domain as the soluble GH-binding protein and leaves behind a cell-associated GHR
      remnant protein containing the transmembrane and cytoplasmic domains. GHR
      metalloproteolysis can be catalyzed by tumor necrosis factor-alpha-converting
      enzyme (ADAM-17) and is associated with down-modulation of GH signaling. We now
      study the fate of the GHR remnant protein. By anti-GHR cytoplasmic domain
      immunoblotting, we observed that the remnant induced in response to phorbol ester
      or platelet-derived growth factor has a reliable pattern of appearance and
      disappearance in both mouse preadipocytes endogenously expressing GHR and
      transfected fibroblasts expressing rabbit GHR. Lactacystin, a specific proteasome
      inhibitor, did not appreciably change the time course of remnant appearance or
      clearance but allowed detection of the GHR stub, a receptor fragment slightly
      smaller than the remnant but containing the C terminus of the remnant (receptor
      cytoplasmic domain). In contrast, MG132, another (less specific) proteasome
      inhibitor, strongly inhibited remnant clearance and prevented stub appearance.
      Inhibitors of gamma-secretase, an aspartyl protease, also prevented the
      appearance of the stub, even in the presence of lactacystin, and concomitantly
      inhibited remnant clearance in the same fashion as MG132. In addition, mouse
      embryonic fibroblasts derived from presenilin 1 and 2 (PS1/2) knockouts
      recapitulated the gamma-secretase inhibitor studies, as compared with their
      littermate controls (PS1/2 wild type). Confocal microscopy indicated that the GHR
      cytoplasmic domain became localized to the nucleus in a fashion dependent on
      PS1/2 activity. These data indicate that the GHR is subject to sequential
      proteolysis by metalloprotease and gamma-secretase activities and may suggest GH
      independent roles for the GHR.

PMID- 15743768
TI  - Covalent cross-links between the gamma subunit (FXYD2) and alpha and beta
      subunits of Na,K-ATPase: modeling the alpha-gamma interaction.
AB  - This study describes specific intramolecular covalent cross-linking of the gamma
      to alpha and gamma to beta subunits of pig kidney Na,K-ATPase and rat gamma to
      alpha co-expressed in HeLa cells. For this purpose pig gammaa and gammab
      sequences were determined by cloning and mass spectrometry. Three bifunctional
      reagents were used: N-hydroxysuccinimidyl-4-azidosalicylic acid (NHS-ASA),
      disuccinimidyl tartrate (DST), and 1-ethyl-3-[3dimethylaminopropyl]carbodiimide
      (EDC). NHS-ASA induced alpha-gamma, DST induced alpha-gamma and beta-gamma, and
      EDC induced primarily beta-gamma cross-links. Specific proteolytic and Fe(2+)
      catalyzed cleavages located NHS-ASA- and DST-induced alpha-gamma cross-links on
      the cytoplasmic surface of the alpha subunit, downstream of His(283) and upstream
      of Val(440). Additional considerations indicated that the DST-induced and NHS-ASA
      induced cross-links involve either Lys(347) or Lys(352) in the S4 stalk segment.
      Mutational analysis of the rat gamma subunit expressed in HeLa cells showed that
      the DST-induced cross-link involves Lys(55) and Lys(56) in the cytoplasmic
      segment. DST and EDC induced two beta-gamma cross-links, a major one at the
      extracellular surface within the segment Gly(143)-Ser(302) of the beta subunit
      and another within Ala(1)-Arg(142). Based on the cross-linking and other data on
      alpha-gamma proximities, we modeled interactions of the transmembrane alpha-helix
      and an unstructured cytoplasmic segment SKRLRCGGKKHR of gamma with a homology
      model of the pig alpha1 subunit. According to the model, the transmembrane
      segment fits in a groove between M2, M6, and M9, and the cytoplasmic segment
      interacts with loops L6/7 and L8/9 and stalk S5.

PMID- 15743769
TI  - Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx
      1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess
      formation of functional transcriptional complexes.
AB  - The homeodomain factor Pdx-1 regulates an array of genes in the developing and
      mature pancreas, but whether regulation of each specific gene occurs by a direct
      mechanism (binding to promoter elements and activating basal transcriptional
      machinery) or an indirect mechanism (via regulation of other genes) is unknown.
      To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we
      performed a kinetic analysis of insulin transcription following adenovirus
      mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma
      cells and pancreatic islets to diminish endogenous Pdx-1 protein. insulin
      transcription was assessed by measuring both a long half-life insulin mRNA
      (mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse
      transcriptase-PCR. Following progressive knock-down of Pdx-1 levels, we observed
      coordinate decreases in pre-mRNA levels (to about 40% of normal levels at 72 h).
      In contrast, mature mRNA levels showed strikingly smaller and delayed declines,
      suggesting that the longer half-life of this species underestimates the
      contribution of Pdx-1 to insulin transcription. Chromatin immunoprecipitation
      assays revealed that the decrease in insulin transcription was associated with
      decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter.
      Although there was no corresponding change in the recruitment of RNA polymerase
      II to the proximal promoter, its recruitment to the insulin coding region was
      significantly reduced. Our results suggest that Pdx-1 directly regulates insulin
      transcription through formation of a complex with transcriptional coactivators on
      the proximal insulin promoter. This complex leads to enhancement of elongation by
      the basal transcriptional machinery.

PMID- 15743770
TI  - Novel binding epitope for Helicobacter pylori found in neolacto carbohydrate
      chains: structure and cross-binding properties.
AB  - Helicobacter pylori is a bacterium that colonizes the stomach of a majority of
      the global human population causing common gastric diseases like ulcers and
      cancer. It has an unusually complex pattern of binding to various host
      glycoconjugates including interaction with sialylated, sulfated, and fucosylated
      sequences. The present study describes an additional binding epitope comprising
      the neolacto internal sequence of GlcNAcbeta3-Galbeta4GlcNAcbeta. The binding was
      detected on TLC plates as an interaction with a seven-sugar ganglioside of rabbit
      thymus. The glycolipid was purified and characterized as
      Neu5Gcalpha3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta3-Galbeta4Glcbeta1Cer with less
      than 10% of the fraction carrying a repeated lacto (type-1) core chain,
      Galbeta3Glc-NAcbeta3Galbeta3GlcNAcbeta. After stepwise chemical and enzymatic
      degradation and structural analysis of products the strongest binder was found to
      be the pentaglycosylceramide GlcNAcbeta3Galbeta4GlcNAcbeta3Galbeta4Glcbeta1-Cer,
      whereas the hexa- and tetraglycosylceramides were less active, and the
      trihexosylceramide was inactive. Further studies revealed that the terminal
      GlcNAcbeta of the pentaglycosylceramide may be exchanged for either GalNAcbeta3,
      GalNAcalpha3, or Galalpha3 without loss of the activity. Calculated minimum
      energy conformers of these four isoreceptors show a substantial topographical
      similarity suggesting that this binding is a result of a molecular mimicry.
      Although the glycoconjugate composition of human gastric epithelial cells is not
      known in detail it is proposed that repeating N-acetyllactosamine units of
      glycoconjugates may serve as bacterial attachment sites in the stomach.

PMID- 15743771
TI  - Roles of phosphorylation-dependent and -independent mechanisms in the regulation
      of M1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2
      in hippocampal neurons.
AB  - When co-expressed with the inositol 1,4,5-trisphosphate biosensor eGFP-PH(PLC
      delta), G protein-coupled receptor kinase 2 (GRK2) can suppress M1 muscarinic
      acetylcholine (mACh) receptor-mediated phospholipase C signaling in hippocampal
      neurons through a phosphorylation-independent mechanism, most likely involving
      the direct binding of the RGS homology domain of GRK2 to G alpha(q/11). To define
      the importance of this mechanism in comparison with classical, phosphorylation
      dependent receptor regulation by GRKs, we have examined M1 mACh receptor
      signaling in hippocampal neurons following depletion of GRK2 and also in the
      presence of non-G alpha(q/11)-binding GRK2 mutants. Depletion of neuronal GRK2
      using an antisense strategy almost completely inhibited M1 mACh receptor
      desensitization without enhancing acute agonist-stimulated phospholipase C
      activity. By stimulating neurons with a submaximal agonist concentration before
      (R1) and after (R2) a period of exposure to a maximal agonist concentration, an
      index (R2/R1) of agonist-induced desensitization of signaling could be obtained.
      Co-transfection of neurons with either a non-G alpha(q/11)-binding (D110A) GRK2
      mutant or the catalytically inactive (D110A,K220R)GRK2 did not suppress acute M1
      mACh receptor-stimulated inositol 1,4,5-trisphosphate production. However, using
      the desensitization (R2/R1) protocol, it could be shown that expression of
      (D110A)GRK2 enhanced, whereas (D110A,K220R)GRK2 inhibited, agonist-induced M1
      mACh receptor desensitization. In Chinese hamster ovary cells, the loss of G
      alpha(q/11) binding did not affect the ability of the (D110A)GRK2 mutant to
      phosphorylate M1 mACh receptors, whereas expression of (D110A,K220R)GRK2 had no
      effect on receptor phosphorylation. These data indicate that in hippocampal
      neurons endogenous GRK2 is a key regulator of M1 mACh receptor signaling and that
      the regulatory process involves both phosphorylation-dependent and -independent
      mechanisms.

PMID- 15743773
TI  - Transient homodimer interactions studied using the electron self-exchange
      reaction.
AB  - Transient homodimer protein interactions have been investigated by analyzing the
      influence of ionic strength (NaCl) on the electron self-exchange (the bimolecular
      reaction whereby the two oxidation states of a redox protein interconvert) rate
      constant (k(ese)) of four plastocyanins. The k(ese) values for the plastocyanins
      from spinach, Dryopteris crassirhizoma (a fern), and the green alga Ulva pertusa,
      which possess acidic patches of varying size and locations, increase 190-, 29-,
      and 21-fold, respectively, at elevated ionic strength (I = 2.03 M). In contrast,
      the k(ese) for the almost neutral cyanobacterial plastocyanin from Anabaena
      variabilis exhibits very little dependence on ionic strength. The temperature
      dependence of the k(ese) for spinach plastocyanin (I = 0.28 M) provides evidence
      for poor packing at the homodimer interface. Representative structures of the
      transient homodimers involved in electron self-exchange, which are consistent
      with fits of the ionic strength dependence of k(ese) to van Leeuwen theory, have
      been obtained from protein modeling and docking simulations. The Coulombic energy
      of the docked homodimers follows the order spinach > D. crassirhizoma > U.
      pertusa > A. variabilis, which matches that of the overall influence of ionic
      strength on k(ese). Analysis of the homodimer structures indicates that poor
      packing and high planarity are features of the interface that favor transient
      interactions. The physiologically relevant Mg2+ ion has a much more pronounced
      influence on the k(ese) of spinach plastocyanin, which along with the known
      properties of the thylakoid lumen suggests a biological role for electron self
      exchange.

PMID- 15743772
TI  - Regulatory serine residues mediate phosphorylation-dependent and phosphorylation
      independent activation of interferon regulatory factor 7.
AB  - Interferon regulatory factor (IRF)7 is a key transcription factor required for
      establishment of antiviral resistance. In response to infection, IRF7 is
      activated by phosphorylation through the action of the non-canonical IkappaB
      kinases, IkappaB kinase-epsilon and TANK-binding kinase 1. Activation leads to
      nuclear retention, DNA binding, and derepression of transactivation ability.
      Clusters of serine residues located in the carboxyl-terminal regulatory domain of
      IRF7 are putative targets of virus-activated kinases. However, the exact sites of
      phosphorylation have not yet been established. Here, we report a comprehensive
      structure-activity examination of potential IRF7 phosphorylation sites through
      analysis of mutant proteins in which specific serine residues were altered to
      alanine or aspartate. Phosphorylation patterns of these mutants were analyzed by
      two-dimensional gel electrophoresis, and their transcriptional activity was
      monitored by reporter assays. Essential phosphorylation events were mapped to
      amino acids 437-438 and a redundant set of sites at either amino acids 429-431 or
      441. IRF7 recovered from infected cells was heterogeneously phosphorylated at
      these sites, and greater phosphorylation correlated with increased
      transactivation. Interestingly, a distinct serine cluster conserved in the
      related protein IRF3 was also essential for IRF7 activation and distal
      phosphorylation. However, the essential role of this motif did not appear to be
      fulfilled by phosphorylation. Rather, these serine residues and an adjacent
      leucine were required for phosphorylation at distal sites and may determine a
      conformational element required for function.

PMID- 15743774
TI  - Artificial zinc finger fusions targeting Sp1-binding sites and the trans
      activator-responsive element potently repress transcription and replication of
      HIV-1.
AB  - Tat activates transcription by interacting with Sp1, NF-kappaB, positive
      transcription elongation factor b, and trans-activator-responsive element (TAR).
      Tat and Sp1 play major roles in transcription by protein-protein interactions at
      human immunodeficiency virus, type 1 (HIV-1) long terminal repeat. Sp1 activates
      transcription by interacting with cyclin T1 in the absence of Tat. To disrupt the
      transcription activation by Tat and Sp1, we fused Sp1-inhibiting polypeptides,
      zinc finger polypeptide, and the TAR-binding mutant Tat (TatdMt) together. A
      designed or natural zinc finger and Tat mutant fusion was used to target the
      fusion to the key regulatory sites (GC box and TAR) on the long terminal repeat
      and nascent short transcripts to disrupt the molecular interaction that normally
      result in robust transcription. The designed zinc finger and TatdMt fusions were
      targeted to the TAR, and they potently repressed both transcription and
      replication of HIV-1. The Sp1-inhibiting POZ domain, TatdMt, and zinc fingers are
      key functional domains important in repression of transcription and replication.
      The designed artificial zinc fingers were targeted to the high affinity Sp1
      binding site, and by being fused with TatdMt and POZ domain, they strongly block
      both Sp1-cyclin T1-dependent transcription and Tat-dependent transcription, even
      in the presence of excess expressed Tat.

PMID- 15743775
TI  - Protein kinase C activates human lipocalin-type prostaglandin D synthase gene
      expression through de-repression of notch-HES signaling and enhancement of AP-2
      beta function in brain-derived TE671 cells.
AB  - Here we investigated the regulatory mechanism of lipocalin-type prostaglandin D
      synthase (L-PGDS) gene expression in human TE671 (medulloblastoma of cerebellum)
      cells. Reporter analysis of the promoter region from -730 to +75 of the human L
      PGDS gene demonstrated that deletion or mutation of the N-box at -337 increased
      the promoter activity 220-300%. The N-box was bound by Hes-1, a mammalian
      homologue of Drosophila Hairy and enhancer of split, as examined by
      electrophoretic mobility shift assay and chromatin immunoprecipitation assay.
      Functional expression of the Notch intracellular domain significantly increased
      Hes-1 expression and decreased L-PGDS expression level in TE671 cells. Moreover,
      knock-down of Hes-1 mRNA by RNA interference significantly enhanced the L-PGDS
      mRNA level, indicating that the L-PGDS gene expression is repressed by the Notch
      Hes signaling. When the AP-2 element at -98 of the promoter region was deleted or
      mutated, the promoter activity was drastically decreased to approximately 10% of
      normal. The AP-2 element was bound by AP-2beta dominantly expressed in TE671
      cells, according to the results of electrophoretic mobility shift assay and
      chromatin immunoprecipitation assay. L-PGDS expression was induced by 12-O
      tetradecanoylphorbol-13-acetate in TE671 cells, and this induction was inhibited
      by a protein kinase C inhibitor. Stimulation of TE671 cells with 12-O
      tetradecanoylphorbol-13-acetate or transfection with protein kinase Calpha
      expression vector induced phosphorylation of Hes-1, inhibition of DNA binding of
      Hes-1 to the N-box, and activation of the AP-2beta function to up-regulate L-PGDS
      gene expression. These results reveal a novel transcriptional regulatory
      mechanism responsible for the high level expression of the human L-PGDS gene in
      TE671 cells.

PMID- 15743776
TI  - Plasminogen activation/plasmin in rheumatoid arthritis: matrix degradation and
      more.
AB  - Rheumatoid arthritis (RA) is one of the most common and most debilitating joint
      diseases, producing high personal, social, and economic costs.(1,2) Patients with
      RA suffer pain and functional losses, often followed by disability and premature
      death. Although the etiology of RA is unknown, substantial efforts have been
      directed toward studying the transition of the joint from normal to diseased. The
      maintenance of normal joint architecture and function requires equilibrium
      between the synthesis and degradation of the specialized extracellular matrices
      that make up bone, cartilage, and tendons. In RA, the balance of tissue
      remodeling is disturbed,(3) and excessive proteolytic degradation of the joint
      matrices leads to joint destruction.(4,5) The early phase of RA is characterized
      by the infiltration of immune and inflammatory cells into the synovium and by
      hyperplasia of the fibroblasts in the synovial lining. This leads to pannus
      formation, cartilage breakdown, and eventual bone destruction.(1,2) Through the
      use of an experimental mouse model of RA, Li and colleagues(6) have implicated
      plasmin as an essential component of the early phase of RA, as reported in this
      issue of The American Journal of Pathology.

PMID- 15743777
TI  - SOD inactivation in asthma: bad or no news?

PMID- 15743778
TI  - Elevated endothelial nitric oxide bioactivity and resistance to angiotensin
      dependent hypertension in 12/15-lipoxygenase knockout mice.
AB  - 12/15-Lipoxygenase (12/15-LOX) plays a pathogenic role in atherosclerosis. To
      characterize whether 12/15-LOX also contributes to endothelial dysfunction and
      hypertension, regulation of vessel tone and angiotensin II (ang II) responses
      were characterized in mice deficient in 12/15-LOX. There was a twofold increase
      in the magnitude of l-nitroarginine-methyl ester-inhibitable, acetylcholine
      dependent relaxation or phenylephrine-dependent constriction in aortic rings
      isolated from 12/15-LOX(-/-) mice. Plasma NO metabolites and aortic endothelial
      NO synthase (eNOS) expression were also elevated twofold. Angiotensin II failed
      to vasoconstrict 12/15-LOX(-/-) aortic rings in the absence of L-nitroarginine
      methyl ester, and ang II impaired acetylcholine-induced relaxation in wild-type,
      but not 12/15-LOX(-/-) rings. In vivo, 12/15-LOX(-/-) mice had similar basal
      systolic blood pressure measurements to wild type, however, blood pressure
      elevations in response to ang II infusion (1.1 mg/kg/day) were significantly
      attenuated (maximal pressure, 143.4 +/- 4 mmHg versus 122.1 +/- 5.3 mmHg for wild
      type and 12/15-LOX(-/-), respectively). In contrast, vascular hypertrophic
      responses to ang II, and ang II type 1 receptor (AT1-R) expression were similar
      in both strains. This study shows that 12/15-LOX(-/-) mice have increased NO
      biosynthesis and impaired ang II-dependent vascular responses in vitro and in
      vivo, suggesting that 12/15-LOX signaling contributes to impaired NO bioactivity
      in vascular disease in vivo.

PMID- 15743779
TI  - Superoxide dismutase inactivation in pathophysiology of asthmatic airway
      remodeling and reactivity.
AB  - Airway hyperresponsiveness and remodeling are defining features of asthma. We
      hypothesized that impaired superoxide dismutase (SOD) antioxidant defense is a
      primary event in the pathophysiology of hyperresponsiveness and remodeling that
      induces apoptosis and shedding of airway epithelial cells. Mechanisms leading to
      apoptosis were studied in vivo and in vitro. Asthmatic lungs had increased
      apoptotic epithelial cells compared to controls as determined by terminal dUTP
      nick-end labeling-positive cells. Apoptosis was confirmed by the finding that
      caspase-9 and -3 and poly (ADP-ribose) polymerase were cleaved. On the basis that
      SOD inactivation triggers cell death and low SOD levels occur in asthma, we
      tested whether SOD inactivation plays a role in airway epithelial cell death. SOD
      inhibition increased cell death and cleavage/activation of caspases in bronchial
      epithelial cells in vitro. Furthermore, oxidation and nitration of MnSOD were
      identified in the asthmatic airway, correlating with physiological parameters of
      asthma severity. These findings link oxidative and nitrative stress to loss of
      SOD activity and downstream events that typify asthma, including apoptosis and
      shedding of the airway epithelium and hyperresponsiveness.

PMID- 15743780
TI  - CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic
      injury.
AB  - Bone marrow-derived cells are known to play important roles in
      repair/regeneration of injured tissues, but their roles in pathological fibrosis
      are less clear. Here, we report a critical role for the chemokine receptor CCR2
      in the recruitment and activation of lung fibrocytes (CD45(+), CD13(+), collagen
      1(+), CD34(-)). Lung fibrocytes were isolated in significantly greater numbers
      from airspaces of fluorescein isothiocyanate-injured CCR2(+/+) mice than from
      CCR2(-/-) mice. Transplant of CCR2(+/+) bone marrow into CCR2(-/-) recipients
      restored recruitment of lung fibrocytes and susceptibility to fibrosis. Ex vivo
      PKH-26-labeled CCR2(+/+) lung fibrocytes also migrated to injured airspaces of
      CCR2(-/-) recipients in vivo. Isolated lung fibrocytes expressed CCR2 and
      migrated to CCL2, and CCL2 stimulated collagen secretion by lung fibrocytes.
      Fibrocytes could transition into fibroblasts in vitro, and this transition was
      associated with loss of CCR2 expression and enhanced production of collagen 1.
      This is the first report describing expression of CCR2 on lung fibrocytes and
      demonstrating that CCR2 regulates both recruitment and activation of these cells
      after respiratory injury.

PMID- 15743781
TI  - Relationship of acute lung inflammatory injury to Fas/FasL system.
AB  - There is mounting evidence that apoptosis plays a significant role in tissue
      damage during acute lung injury. To evaluate the role of the apoptosis mediators
      Fas and FasL in acute lung injury, Fas (lpr)- or FasL (gld)-deficient and wild
      type mice were challenged with intrapulmonary deposition of IgG immune complexes.
      Lung injury parameters ((125)I-albumin leak, accumulation of myeloperoxidase, and
      wet lung weights) were measured and found to be consistently reduced in both lpr
      and gld mice. In wild-type mice, lung injury was associated with a marked
      increase in Fas protein in lung. Inflamed lungs of wild-type mice showed striking
      evidence of activated caspase-3, which was much diminished in inflamed lungs from
      lpr mice. Intratracheal administration of a monoclonal Fas-activating antibody
      (Jo2) in wild-type mice induced MIP-2 and KC production in bronchoalveolar lavage
      fluids, and a murine alveolar macrophage cell line (MH-S) showed significantly
      increased MIP-2 production after incubation with this antibody. Bronchoalveolar
      lavage fluid content of MIP-2 and KC was substantially reduced in lpr mice after
      lung injury when compared to levels in wild-type mice. These data suggest that
      the Fas/FasL system regulates the acute lung inflammatory response by positively
      affecting CXC-chemokine production, ultimately leading to enhanced neutrophil
      influx and tissue damage.

PMID- 15743782
TI  - Nuclear factor-kappaB1 (p50) limits the inflammatory and fibrogenic responses to
      chronic injury.
AB  - In this study we addressed the role of the nuclear factor (NF)-kappaB1/p50
      subunit in chronic injury of the liver by determining the inflammatory and
      fibrotic responses of nfkappab1-null mice in an experimental model that mimics
      chronic liver disease. Mice received repeated hepatic injuries throughout 12
      weeks by intraperitoneal injection of the hepatotoxin carbon tetrachloride. In
      response nfkappab1(-/-) mice developed more severe neutrophilic inflammation and
      fibrosis compared to nfkappab1(+/+) mice. This phenotype was associated with
      elevated hepatic expression of tumor necrosis factor (TNF)-alpha, which was
      localized to regions of the liver associated with inflammation and fibrosis.
      Hepatic stellate cells are important regulators of hepatic inflammatory and
      fibrogenic events but normally do not express TNF-alpha. Hepatic stellate cells
      derived from nfkappab1(-/-) mice expressed TNF-alpha promoter activity, mRNA, and
      protein. By contrast the expression of other NF-kappaB-responsive genes (ICAM1
      and interleukin-6) was similar between nfkappab1(-/-) and nfkappab1(+/+) cells.
      We provide experimental evidence that the inappropriate expression of TNF-alpha
      by nfkappab1(-/-) cells is because of lack of a p50-dependent histone deacetylase
      1 (HDAC1)-mediated repression of TNF-alpha gene transcription. Taken together
      these data indicate that the p50 NF-kappaB subunit plays a critical protective
      role in the injured liver by limiting the expression of TNF-alpha and its
      recruitment of inflammatory cells.

PMID- 15743783
TI  - Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing
      differentiation into hepatocytes.
AB  - Oval cells of the liver participate in liver regeneration when hepatocytes are
      prevented from proliferating in response to liver damage. To clarify the role of
      oncostatin M (OSM) in the liver regeneration involving oval cells, we examined
      the expression of OSM and OSM-specific receptor (OSM-R) in the liver undergoing
      regeneration in the 2-acetylaminofluorene/partial hepatectomy model. Expression
      levels of OSM-R changed in correlation to the number of oval cells, and its
      expression was exclusively observed in oval cells. On the other hand, OSM was
      expressed in both oval cells and Kupffer cells. To examine the effect of OSM on
      the growth and differentiation of oval cells, rat oval cells (OC15-5) were
      incubated in conditioned medium of 293T cells expressing rat OSM cDNA. This
      resulted in suppression of growth, changes in morphology (microvilli and large
      cytoplasm with developed organelles), and expression of hepatocyte markers
      (albumin, tyrosine amino transferase, and tryptophan oxygenase). The effects of
      the conditioned medium with rat OSM were abrogated by introducing a small
      interfering RNA specifically targeting rat OSM-R into OC15-5 cells. These results
      indicate that OSM is a key mediator for inducing differentiation of OC15-5 cells
      into hepatocytes and suggest that the OSM/OSM-R system is pivotal in the
      differentiation of oval cells into hepatocytes, thereby promoting liver
      regeneration.

PMID- 15743784
TI  - Therapeutic effects of troglitazone in experimental chronic pancreatitis in mice.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma controls growth,
      differentiation, and inflammation. PPAR-gamma agonists exert anti-inflammatory
      effects in vitro and inhibit the activation of pancreas stellate cells,
      implicated in the formation and progression of fibrosis. We determined the
      influence of troglitazone, a ligand for PPAR-gamma, on pancreatic damage and
      fibrosis in experimental chronic pancreatitis. Mice received six hourly
      intraperitoneal injections with 50 microg/kg of cerulein or saline, three times a
      week for 6 weeks. One week after the last injection all mice were sacrificed.
      Untreated mice were compared with mice treated with troglitazone either during
      weeks 1 to 6 or weeks 4 to 6. All mice that received cerulein injections
      displayed histopathological signs of chronic pancreatitis at week 7. Troglitazone
      treatment improved all markers for severity of pancreatitis. Moreover, early and
      postponed troglitazone treatments were equally effective in diminishing
      intrapancreatic fibrosis as quantified by Sirius red staining, hydroxyproline
      content, and laminin staining as well as the increased number of pancreatic
      stellate cells and pancreas levels of transforming growth factor-beta. Thus,
      troglitazone attenuated pancreatic damage and inflammation in experimental
      chronic pancreatitis and remained beneficial in a therapeutic setting when given
      after initial damage had been established.

PMID- 15743785
TI  - An experimental model of autoimmune pancreatitis in the rat.
AB  - Autoimmune pancreatitis (AIP), a recently defined disease of unknown etiology, is
      characterized by inflammatory infiltrates in the pancreas with conspicuous
      involvement of the ducts. The disease clinically manifests in humans as
      epigastric pain, weight loss, and jaundice. This report describes the development
      of a novel animal model of this disease in the rat, which we have termed
      experimental autoimmune pancreatitis. Adoptive transfer of amylase-specific
      CD4(+) T cells was able to confer pancreatitis to naive syngeneic recipient
      animals. No treatments before the adoptive transfer of T cells were necessary for
      disease to ensue, and the severity of disease was proportional to the number of T
      cells administered. The pancreatic lesions of rats with experimental autoimmune
      pancreatitis were characterized histologically as overwhelmingly lymphocytic with
      occasional plasma cells, neutrophils, and mast cells. Acinar tissue destruction
      and ductular inflammation were common features, with less frequent involvement of
      larger ducts. Immunohistochemical analysis revealed the presence of CD4(+) T
      cells in large numbers as well as CD8(+) T cells, macrophages, and dendritic
      cells. Expression of MHC I and MHC II also increased at the site of the lesion.
      Clinically, the disease manifested as either failure to gain weight at a rate
      concomitant with control animals or as outright weight loss. Thus, administration
      of activated CD4(+) T cells specific for the pancreatic enzyme amylase can induce
      pancreatitis in the rat in a manner that is reminiscent of human AIP.

PMID- 15743786
TI  - Complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid
      cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and
      localization.
AB  - Functional inactivation of the tumor suppressor p27(kip1) in human cancer occurs
      either through loss of expression or through phosphorylation-dependent
      cytoplasmic sequestration. Here we demonstrate that dysregulation of the PI3K/AKT
      pathway is important in thyroid carcinogenesis and that p27(kip1) is a key target
      of the growth-regulatory activity exerted by this pathway in thyroid cancer
      cells. Using specific PI3K inhibitors (LY294002, wortmannin, and PTEN) and a
      dominant active AKT construct (myrAKT), we demonstrated that the PI3K/AKT pathway
      controlled thyroid cell proliferation by regulating the expression and
      subcellular localization of p27. Results obtained with phospho-specific
      antibodies and with transfection of nonphosphorylable p27(kip1) mutant constructs
      demonstrated that PI3K/AKT-dependent regulation of p27(kip1) mislocalization in
      thyroid cancer cells occurred via phosphorylation of p27(kip1) at T157 and T198
      (but not at S10 or T187). Finally, we evaluated whether these results were
      applicable to human tumors. Analysis of 100 thyroid carcinomas indicated that
      p27(kip1) phosphorylation at T157/T198 and cytoplasmic mislocalization were
      preferentially associated with activation of the PI3K/AKT pathway. Thus the
      PI3/AKT pathway and its effector p27(kip1) play major roles in thyroid
      carcinogenesis.

PMID- 15743787
TI  - Colon cancer cell-derived high mobility group 1/amphoterin induces growth
      inhibition and apoptosis in macrophages.
AB  - High mobility group (HMGB)1/amphoterin is a multifunctional cytokine involved in
      invasion and metastasis of cancer and in inflammation. To investigate
      HMGB1/amphoterin effects on macrophages, U937 human monocytic leukemia cells and
      rat peritoneal and human alveolar macrophages were examined. U937 cells expressed
      low levels of an HMGB1/amphoterin receptor, receptor for advanced glycation end
      products (RAGE), whereas RAGE production was induced in differentiated phorbol 12
      myristate 13-acetate (PMA)-U937 cells. Treatment with cultured medium of
      HMGB1/amphoterin-secreting WiDr human colon cancer cells showed growth inhibition
      of both U937 and PMA-U937 cells and apoptosis in PMA-U937 cells. The number of
      PMA-U937 cells was markedly decreased by co-culture with WiDr cells exposed to
      HMGB1/amphoterin sense S-oligodeoxynucleotide (ODN) in spheroids or monolayers.
      In contrast, PMA-U937 cells co-cultured with WiDr cells exposed to
      HMGB1/amphoterin anti-sense S-ODN were preserved in number. PMA-U937 cells
      exposed to RAGE anti-sense S-ODN were insensitive to WiDr-cultured medium.
      Recombinant human HMGB1/amphoterin induced growth inhibition in thioglycollate
      induced rat peritoneal macrophages, PMA-U937 cells, and human alveolar
      macrophages, an effect that was abrogated by absorption with anti-HMGB1 antibody.
      Phosphorylation of JNK and Rac1 was induced in PMA-U937 cells treated with
      HMGB1/amphoterin. These results suggest that HMGB1/amphoterin induces growth
      inhibition and apoptosis in macrophages through RAGE intracellular signaling
      pathway.

PMID- 15743788
TI  - Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks
      transforming growth factor-beta signaling and fibrosis in rat remnant kidney.
AB  - Transforming growth factor (TGF)-beta1 has been shown to play a critical role in
      hypertensive nephropathy. We hypothesized that blocking TGF-beta1 signaling could
      attenuate renal fibrosis in a rat model of remnant kidney disease. Groups of six
      rats were subjected to 5/6 nephrectomy and received renal arterial injection of a
      doxycycline-regulated Smad7 gene or control empty vector using an ultrasound
      microbubble-mediated system. Smad7 transgene expression within the kidney was
      tightly controlled by the addition of doxycycline in the daily drinking water.
      All animals were euthanized at week 4 for renal functional and histological
      examination. Hypertension of equivalent magnitude (190 to 200 mmHg) developed in
      both Smad7- and empty vector-treated rats. However, treatment with Smad7
      substantially inhibited Smad2/3 activation and prevented progressive renal injury
      by inhibiting the rise of 24-hour proteinuria (P < 0.001) and serum creatinine (P
      < 0.001), preserving creatinine clearance (P < 0.05), and attenuating renal
      fibrosis and vascular sclerosis such as collagen I and III expression (P < 0.01)
      and myofibroblast accumulation (P < 0.001). In conclusion, TGF-beta/Smad
      signaling plays a critical role in renal fibrosis in a rat remnant kidney model.
      The ability of Smad7 to block Smad2/3 activation and attenuate renal and vascular
      sclerosis demonstrates that ultrasound-mediated Smad7 gene therapy may be a
      useful therapeutic strategy for the prevention of renal fibrosis in association
      with hypertension.

PMID- 15743789
TI  - Sphingosine-1-phosphate inhibits nuclear factor kappaB activation and germ cell
      apoptosis in the human testis independently of its receptors.
AB  - Early apoptosis-inducing events are potentially important targets for preventing
      germ cell loss caused by external stress. The sphingolipid sphingosine-1
      phosphate (S1P) is an important regulator of stress-induced apoptosis. It affects
      the cell as an intracellular signaling molecule or as a ligand to its cell
      membrane-bound S1P(1-5) receptors. We previously demonstrated that S1P inhibits
      stress-induced male germ cell death in vitro and in vivo. Here, we further define
      the mechanisms of S1P-mediated inhibition of male germ cell death. Using
      immunohistochemistry, we detected expression of the S1P(1) and S1P(2) receptors
      in the somatic Sertoli cells of the human testis. In a culture of human
      seminiferous tubules, S1P inhibited germ cell apoptosis, suppressed both nuclear
      factor kappaB (NF-kappaB) DNA-binding activity and expression of phosphorylated
      Akt, but did not affect activator protein-1 (AP-1) DNA-binding activity. Dihydro
      S1P, which binds to and activates S1P receptors but has no direct intracellular
      effect, suppressed neither apoptosis nor NF-kappaB activity. These results
      suggest that S1P inhibits male germ cell apoptosis independently of its
      receptors, possibly by inhibiting the transcription factor NF-kappaB and Akt
      phosphorylation.

PMID- 15743790
TI  - The plasminogen activator/plasmin system is essential for development of the
      joint inflammatory phase of collagen type II-induced arthritis.
AB  - The plasminogen activator (PA) system has been proposed to have important roles
      in rheumatoid arthritis. Here we have used the autoimmune collagen type II (CII)
      induced arthritis (CIA) model and mice deficient for urokinase-type PA (uPA) or
      plasminogen to investigate the role of the PA system for development of
      arthritis. Our data revealed that uPA-deficient mice have a lower severity and
      incidence of CIA than wild-type mice. Furthermore, although >80% of wild-type
      control mice developed CIA, we found that none of the 50 plasminogen-deficient
      littermates that were tested developed CIA within a 40-day period. Antibody
      generation after CII immunization as well as the binding of labeled anti-CII
      antibodies to the surface of cartilage were similar in wild-type and plasminogen
      deficient mice. No sign of inflammation was seen when plasminogen-deficient mice
      were injected with a mixture of monoclonal antibodies against CII. However, after
      daily injections of human plasminogen, these mice developed arthritis within 5
      days. Our finding that infiltration of inflammatory cells into the synovial
      joints was impaired in plasminogen-deficient mice suggests that uPA and
      plasminogen are important mediators of joint inflammation. Active plasmin is
      therefore essential for the induction of pathological inflammatory joint
      destruction in CIA.

PMID- 15743791
TI  - Vascular adhesion protein-1 is involved in both acute and chronic inflammation in
      the mouse.
AB  - Vascular adhesion protein-1 (VAP-1) is an endothelial molecule that possesses
      both adhesive and enzymatic properties in vitro. So far, however, elucidation of
      its in vivo function has suffered from the lack of function-blocking reagents
      that are suitable for use in animal models. In this work we produced monoclonal
      antibodies against murine VAP-1 and characterized them using in vitro binding
      assays. We then examined whether the antibodies could prevent leukocyte migration
      in in vivo inflammation models, including two acute models (peritonitis induced
      with proteose peptone and interleukin-1 and air pouch inflammation enhanced by
      CCL21) and one chronic model (autoimmune diabetes in nonobese diabetic mice).
      Antibodies 7-88 and 7-106 inhibited migration of granulocytes and monocytes in
      both acute models of inflammation. Strikingly, antibody 7-88 significantly
      prevented diabetes in a subset of nonobese diabetic mice. The results show for
      the first time that in mouse models of inflammation, VAP-1 mediates leukocyte
      trafficking to sites of inflammation and thus is a potential target for anti
      inflammatory therapies.

PMID- 15743792
TI  - Virus-specific antibody, in the absence of T cells, mediates demyelination in
      mice infected with a neurotropic coronavirus.
AB  - Mice infected with mouse hepatitis virus strain JHM develop an inflammatory
      demyelinating disease in the central nervous system with many similarities to
      human multiple sclerosis. The mouse disease is primarily immune-mediated because
      demyelination is not detected in JHM-infected mice lacking T or B cells but does
      occur after transfer of JHM-specific T cells. Although less is known about the
      ability of antibodies to mediate demyelination, the presence of oligoclonally
      expanded B cells and high concentrations of antibodies (against self or
      infectious agents) in the central nervous system of many multiple sclerosis
      patients suggests that antibodies may also contribute to myelin destruction.
      Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused
      demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to
      areas of demyelination, consistent with a direct interaction between antibody and
      infected cells. Demyelination was reduced by 85 to 90% in infected RAG1(-/-) mice
      lacking normal expression of activating Fc receptors (FcRgamma(-/-)) and by
      approximately 76% when complement was depleted by treatment with cobra venom
      factor. These data demonstrate that JHM-specific antibodies are sufficient to
      cause demyelination and that myelin destruction in the presence of anti-virus
      antibodies results from a combination of complement- and Fc receptor-dependent
      mechanisms.

PMID- 15743793
TI  - Abnormal T-cell reactivity against paternal antigens in spontaneous abortion:
      adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents
      fetal rejection in a murine abortion model.
AB  - Mammalian pregnancy is thought to be a state of immunological tolerance. The
      mechanisms underlying this phenomenon are still poorly understood. Here, we
      determined whether an inappropriate function of T regulatory (Treg) cells is
      involved in the pathogenesis of spontaneous abortion. We evaluated spleen and
      decidual lymphocytes from CBA/J mice undergoing immunological abortion (DBA/2J
      mated) or having normal pregnancy (BALB/c-mated) on day 14 of gestation for ex
      vivo cytokine production after PMA or paternal antigen (alloantigen) stimulation.
      Treg activity was characterized by quantifying CD4(+)CD25(+) cells, foxp3
      expression, and interleukin-10 secretion. Decidual lymphocytes from abortion
      CBA/J mice contained a significantly higher frequency of interferon-gamma
      producing T cells specific for paternal antigens compared to those from normal
      pregnancy (7.8% versus 2.7%, P < 0.05). Compared to virgin CBA/J females, normal
      pregnant mice showed strongly elevated numbers of CD4(+)CD25(+) and interleukin
      10(+) Treg cells in the thymus whereas significantly lower frequencies of Treg
      cells were observed in abortion mice. Very interestingly, CD4(+)CD25(+) Treg
      cells from normal pregnant and nonpregnant CBA/J mice could inhibit both
      proliferation and interferon-gamma secretion of lymphocytes from abortion mice in
      vitro whereas in vivo prevention of fetal rejection could only be achieved after
      adoptive transfer of Treg cells from normal pregnant mice. Our data suggest that
      pregnancy-induced Treg cells play a vital role in maternal tolerance to the
      allogeneic fetus.

PMID- 15743794
TI  - Functional erythropoietin autocrine loop in melanoma.
AB  - Although erythropoietin (Epo) is a known stimulator of erythropoiesis, recent
      evidence suggests that its biological functions are not confined to hematopoietic
      cells. To elucidate the role of Epo and erythropoietin receptor (EpoR) in
      melanoma, we examined the expression and function of these proteins in
      melanocytes and melanoma cells. We found increased expression of Epo in melanoma
      cells compared to melanocyte in vitro. EpoR was also strongly expressed in all of
      the melanoma cell lines and two of the three melanocyte cell lines examined. Epo
      expression was significantly higher in melanoma than in benign nevi as determined
      by immunohistochemistry. Although melanoma cells secreted Epo in normoxic
      condition in vitro, hypoxia and CoCl(2) treatment increased Epo secretion. EpoR
      in melanoma cells was functional, because exogenous Epo increased melanoma
      resistance to hypoxic stress, pretreatment of melanoma cells with Epo
      significantly increased resistance to dacarbazine treatment, and Epo increased
      the phosphorylation of EpoR, RAF, and MEK. In conclusion, we demonstrated
      constitutive expression of Epo and EpoR as well as autonomous secretion of Epo by
      melanoma cells, indicating a novel autocrine loop of Epo in melanoma. The results
      suggest that the autocrine and paracrine functions of Epo might play a role in
      malignant transformation of melanocytes and in the survival of melanoma cells in
      hypoxia and other adverse conditions.

PMID- 15743795
TI  - Interleukin-6 gene ablation in a transgenic mouse model of malignant skin
      melanoma.
AB  - Interleukin (IL)-6 is a pleiotropic cytokine that has been shown to inhibit the
      growth of early stage and to promote the proliferation of advanced stage melanoma
      cells in vitro. In patients with metastasizing melanomas, highly increased IL-6
      blood levels correlate with a poor response to chemotherapy and a worse overall
      prognosis, suggesting that IL-6 promotes melanoma progression in vivo. Here, we
      analyzed the role of IL-6 in melanoma development and progression in a transgenic
      mouse model. We bred IL-6-deficient mice with MT-ret transgenic animals
      predisposed for melanomas. While MT-ret transgenic animals develop severe
      melanosis of the skin and subcutis and subsequent melanomas at an incidence of
      80% during their first year of life, MT-ret mice devoid of IL-6 developed
      preneoplastic melanosis and consecutive melanomas significantly less frequently
      (47%; P < 0.05). Moreover, the tumors were significantly smaller in the groups of
      MT-ret mice lacking one (P < 0.05) or both (P < 0.01) copies of the IL-6 gene.
      Immunoblot analysis revealed that ret transgene expression was not reduced in the
      skin of mice lacking IL-6, indicating that the observed decrease of melanoma
      incidence and of tumor sizes was not because of a down-regulation of transgene
      expression. Taken together, these results indicate that IL-6 enhances both the
      development of melanoma precursor lesions and the subsequent growth of the
      resulting tumors in the MT-ret model of melanoma development.

PMID- 15743796
TI  - A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice.
AB  - Psoriasis is a common, persistent skin disorder characterized by recurrent
      erythematous lesions thought to arise as a result of inflammatory cell
      infiltration and activation of keratinocyte proliferation. Unscheduled angiogenic
      growth has also been proposed to mediate the pathogenesis of psoriasis although
      the cellular and molecular basis for this response remains unclear. Recently, a
      role for the angiopoietin signaling system in psoriasis has been suggested by
      studies that demonstrate an up-regulation of the tyrosine kinase receptor Tie2
      (also known as Tek) as well as angiopoietin-1 and angiopoietin-2 in human
      psoriatic lesions. To examine temporal expression of Tie2, we have developed a
      binary transgenic approach whereby expression of Tie2 can be conditionally
      regulated by the presence of tetracycline analogs in double-transgenic mice. A
      psoriasis-like phenotype developed in double-transgenic animals within 5 days of
      birth and persisted throughout adulthood. The skin of affected mice exhibited
      many cardinal features of human psoriasis including epidermal hyperplasia,
      inflammatory cell accumulation, and altered dermal angiogenesis. These skin
      abnormalities resolved completely with tetracycline-mediated suppression of
      transgene expression, thereby illustrating a complete dependence on Tie2
      signaling for disease maintenance and progression. Furthermore, the skin lesions
      in double-transgenic mice markedly improved after administration of the
      immunosuppressive anti-psoriatic agent cyclosporine, thus demonstrating the
      clinical significance of this new model.

PMID- 15743797
TI  - The role of protease-activated receptor-1 in bone healing.
AB  - Protease-activated receptor (PAR)-1, a G-protein-coupled receptor activated by
      thrombin, mediates thrombin-induced proliferation of osteoblasts. The current
      study was undertaken to define the role of PAR-1 in bone repair. Holes were
      drilled transversely through the diaphysis of both tibiae of PAR-1-null and wild
      type mice. Three days later, fewer cells had invaded the drill site from adjacent
      bone marrow in PAR-1-null mice than in wild-type mice, and a lower percentage of
      cells were labeled with [(3)H]thymidine in PAR-1-null drill sites. More
      osteoclasts were also observed in the drill site of PAR-1-null mice than in wild
      type mice 7 days after drilling. New mineralized bone area was less in the drill
      site and on the adjacent periosteal surface in PAR-1-null mice than in wild-type
      mice at day 9. From day 14, no obvious differences could be seen between PAR-1
      null and wild-type tibiae. In vitro thrombin caused a dose-dependent increase in
      proliferation of bone marrow stromal cells isolated from wild-type mice but not
      PAR-1-null mice. Thrombin stimulated survival of bone marrow stromal cells from
      both wild-type and PAR-1-null mice, but it did not affect bone marrow stromal
      cell migration in either wild-type or PAR-1-null cells. The results indicate that
      PAR-1 plays an early role in bone repair.

PMID- 15743798
TI  - Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein
      overexpression replicates the characteristic neuropathology of multiple system
      atrophy.
AB  - Multiple system atrophy (MSA) is a progressive neurodegenerative disorder
      characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar
      ataxia, and dysautonomia. Neuropathology shows a characteristic neuronal
      multisystem degeneration that is associated with widespread oligodendroglial
      alpha-synuclein (alpha-SYN) inclusions. Presently no animal model completely
      replicates the specific neuropathology of MSA. Here we investigated the
      behavioral and pathological features resulting from oligodendroglial alpha-SYN
      overexpression in transgenic mice exposed to mitochondrial inhibition by 3
      nitropropionic acid. In transgenic mice 3-nitropropionic acid induced or
      augmented motor deficits that were associated with MSA-like pathology including
      striatonigral degeneration and olivopontocerebellar atrophy. Widespread
      astrogliosis and microglial activation were also observed in the presence of
      alpha-SYN in oligodendrocytes. Our results indicate that combined mitochondrial
      inhibition and overexpression of oligodendroglial alpha-SYN generates a novel
      model of MSA that may be useful for evaluating both pathogenesis and treatment
      strategies.

PMID- 15743799
TI  - Up-regulation of angiopoietin-2, matrix metalloprotease-2, membrane type 1
      metalloprotease, and laminin 5 gamma 2 correlates with the invasiveness of human
      glioma.
AB  - Diffuse infiltration of malignant human glioma cells into surrounding brain
      structures occurs through the activation of multigenic programs. We recently
      showed that angiopoietin-2 (Ang2) induces glioma invasion through the activation
      of matrix metalloprotease-2 (MMP-2). Here, we report that up-regulation of Ang2,
      MMP-2, membrane type 1-MMP (MT1-MMP), and laminin 5 gamma 2 (LN 5 gamma 2) in
      tumor cells correlates with glioma invasion. Analyses of 57 clinical human glioma
      biopsies of World Health Organization grade I to IV tumors displaying a distinct
      invasive edge and 39 glioma specimens that only contain the central region of the
      tumor showed that Ang2, MMP-2, MT1-MMP, and LN 5 gamma 2 were co-overexpressed in
      invasive areas but not in the central regions of the glioma tissues. Statistical
      analyses revealed a significant link between the preferential expression of these
      molecules and invasiveness. Protein analyses of microdissected primary glioma
      tissue showed up-regulation and activation of MT1-MMP and LN 5 gamma 2 at the
      invasive edge of the tumors, supporting this observation. Concordantly, in human
      U87MG glioma xenografts engineered to express Ang2, increased expression of MT1
      MMP and LN 5 gamma 2, along with MMP-2 up-regulation, in actively invading glioma
      cells was also evident. In cell culture, stimulation of glioma cells by
      overexpressing Ang2 or exposure to exogenous Ang2 promoted the expression and
      activation of MMP-2, MT1-MMP, and LN 5 gamma 2. These results suggest that up
      regulation of Ang2, MMP-2, MT1-MMP, and LN 5 gamma 2 is associated with the
      invasiveness displayed by human gliomas and that induction of these molecules by
      Ang2 may be essential for glioma invasion.

PMID- 15743800
TI  - Cross-talk between Schwann cells and neuroblasts influences the biology of
      neuroblastoma xenografts.
AB  - Neuroblastoma (NB) tumors with abundant schwannian stroma have a differentiated
      phenotype, low vascularity, and are associated with a favorable prognosis. These
      observations suggest that cross-talk between Schwann cells and neuroblasts may
      influence tumor biology. To test this hypothesis, we developed a novel NB
      xenograft model with infiltrating mouse Schwann cells. Human SMS-KCNR NB cells
      were injected intrafascicularly (sciatic nerve-engrafted NB, n = 19) or outside
      the sciatic nerve (control, n = 12). Xenografts were harvested 4 to 12 weeks
      after tumor cell inoculation for histological studies. Schwann cells were
      immunostained with S-100 and species-specific p75(NGFR), major histocompatibility
      complex, and human leukocyte antigen antibodies. The number of proliferating
      cells, infiltrating Schwann cells, apoptotic cells, differentiated neuroblasts,
      and blood vessels in the sciatic nerve-engrafted NB tumors were compared to
      controls. Significantly more Schwann cells were detected in the sciatic nerve
      engrafted NB xenografts than controls (P < 0.001). The infiltrating Schwann cells
      were S-100-positive and reacted with anti-mouse major histocompatibility complex
      class Ib and p75(NGFR) but not anti-human p75(NGFR) and human leukocyte antigen
      class I antibodies. The sciatic nerve-engrafted tumors also had lower numbers of
      proliferating neuroblasts, higher numbers of differentiated neuroblasts and
      apoptotic cells, and decreased vascular density compared to controls. Our results
      indicate that infiltrating Schwann cells of mouse origin are capable of promoting
      human neuroblast differentiation, inducing apoptosis, and inhibiting
      proliferation and angiogenesis in vivo.

PMID- 15743801
TI  - Recombinant alpha2(IV)NC1 domain inhibits tumor cell-extracellular matrix
      interactions, induces cellular senescence, and inhibits tumor growth in vivo.
AB  - Cellular interaction with the extracellular matrix is thought to be a critical
      event in controlling angiogenesis and tumor growth. In our previous studies,
      genetically distinct noncollagenous (NC) domains of type-IV collagen were shown
      to interact with integrin receptors expressed on the surface of endothelial
      cells. Moreover, these NC1 domains were shown to inhibit angiogenesis in vivo.
      Here, we provide evidence that a recombinant form of the alpha2(IV)NC1 domain of
      type-IV collagen could bind integrins alpha1beta1 and alphavbeta3 expressed on
      melanoma cells and inhibit tumor cell adhesion in a ligand-specific manner.
      Systemic administration of recombinant alpha2(IV)NC1 domain potently inhibited
      M21 melanoma tumor growth within full thickness human skin and exhibited a dose
      dependent inhibition of tumor growth in nude mice. Interestingly, alpha2(IV)NC1
      domain enhanced cellular senescence in tumor cells in vitro and in vivo. Taken
      together, these results suggest that recombinant alpha2(IV)NC1 domain is not only
      a potent anti-angiogenic reagent, but it also directly impacts tumor cell
      behavior. Thus, alpha2(IV)NC1 domain represents a potent inhibitor of tumor
      growth by impacting both endothelial and tumor cell compartments.

PMID- 15743802
TI  - Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane
      glycoprotein, in human squamous cell carcinomas and germ cell tumors.
AB  - The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but
      not blood vascular endothelial cells in culture and in tumor-associated
      lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and
      impaired lymphatic vascular patterning. However, research into the biological
      importance of podoplanin has been hampered by the lack of a generally available
      antibody against the human protein, and its expression in normal tissues and in
      human malignancies has remained unclear. We generated a human podoplanin-Fc
      fusion protein and found that the commercially available mouse monoclonal
      antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme
      linked immunosorbent assay and Western blot analyses. We found that, in addition
      to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial
      cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal
      reticular cells and follicular dendritic cells of lymphoid organs. These findings
      were confirmed in normal mouse tissues with anti-podoplanin antibody 8.1.1.
      Podoplanin was also strongly expressed by granulosa cells in normal ovarian
      follicles, and by ovarian dysgerminomas and granulosa cell tumors. Although
      podoplanin was primarily absent from normal human epidermis, its expression was
      strongly induced in 22 of 28 squamous cell carcinomas studied. These findings
      suggest a potential role of podoplanin in tumor progression, and they also
      identify the first commercially available antibody for the specific staining of a
      defined lymphatic marker in archival human tissue sections, thereby enabling more
      widespread studies of tumor lymphangiogenesis in human cancers.

PMID- 15743803
TI  - Matricellular homologs in the foreign body response: hevin suppresses
      inflammation, but hevin and SPARC together diminish angiogenesis.
AB  - Implanted foreign materials, used to restore or assist tissue function, elicit an
      initial acute inflammatory response followed by chronic fibrosis that leads to
      the entrapment of the biomaterial in a thick, poorly vascularized collagenous
      capsule. Matricellular proteins, secreted macromolecules that interact with
      extracellular matrix proteins but do not in themselves serve structural roles,
      have been identified as important mediators of the foreign body response that
      includes inflammation, angiogenesis, and collagen synthesis and assembly. In this
      report we delineate functions of hevin and SPARC, two homologs of the SPARC
      family of matricellular proteins, in the foreign body response. Despite their
      sequence similarity, hevin and SPARC mediate different aspects of this fibrotic
      response. Using mice with targeted gene deletions, we show that hevin is central
      to the progression of biomaterial-induced inflammation whereas SPARC regulates
      the formation of the collagenous capsule. Although vascular density within the
      capsule is unaltered in the absence of either protein, SPARC-hevin double-null
      capsules show substantially increased numbers of vessels, indicating compensatory
      functions for these two proteins in the inhibition of angiogenesis. These results
      provide important information for further development of implant technology.

PMID- 15743804
TI  - Therapeutic targeting of endothelial ligands for L-selectin (PNAd) in a sheep
      model of asthma.
AB  - The homing of lymphocytes to peripheral lymph nodes is initiated by an adhesive
      interaction between L-selectin on lymphocytes and PNAd, a set of sialomucins that
      are constitutively displayed on high endothelial venules of lymph nodes. PNAd is
      defined by monoclonal antibody MECA-79 that recognizes a sulfated oligosaccharide
      carried by the sialomucins. This epitope overlaps with 6-sulfo sialyl Lewis x, a
      recognition determinant for L-selectin. Previous work has shown that
      administration of a L-selectin monoclonal antibody blocks both late-phase airway
      responses and airway hyperresponsiveness in a sheep model of asthma. We show here
      that airway-associated lymphoid collections from lungs of allergic sheep
      exhibited PNAd(+) venules as detected by immunostaining with MECA-79. The same
      vessels also expressed a GlcNAc-6-O-sulfotransferase known as HEC-GlcNAc6ST,
      which is known to contribute to the formation of the MECA-79 epitope in high
      endothelial venules of mouse lymph nodes. Intravenous administration of MECA-79
      to allergic sheep significantly blunted both the late-phase airway response and
      airway hyperresponsiveness induced by airway allergen challenge. Furthermore,
      MECA-79 inhibited the accumulation of all classes of leukocytes in
      bronchoalveolar lavage fluid. These findings represent the first demonstration
      that targeting of PNAd has therapeutic efficacy in an inflammatory disease.

PMID- 15743805
TI  - L- and P-selectins collaborate to support leukocyte rolling in vivo when high
      affinity P-selectin-P-selectin glycoprotein ligand-1 interaction is inhibited.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin controls early
      leukocyte rolling during inflammation. Interestingly, antibodies and
      pharmacological inhibitors (eg, rPSGL-Ig) that target the N-terminus of PSGL-1
      reduce but do not abolish P-selectin-dependent leukocyte rolling in vivo whereas
      PSGL-1-deficient mice have almost no P-selectin-dependent rolling. We have
      investigated mechanisms of P-selectin-dependent, PSGL-1-independent rolling using
      intravital microscopy. Initially we used fluorescent microspheres to study the
      potential of L-selectin and the minimal selectin ligand sialyl Lewis(x) (sLe(x))
      to interact with postcapillary venules in the absence of PSGL-1. Microspheres
      coated with combinations of L-selectin and sLe(x) interacted with surgically
      stimulated cremaster venules in a P-selectin-dependent manner. Microspheres
      coated with either L-selectin or sLe(x) alone showed less evidence of
      interaction. We also investigated leukocyte rolling in the presence of PSGL-1
      antibody or inhibitor (rPSGL-Ig), both of which partially inhibited P-selectin
      dependent leukocyte rolling. Residual rolling was substantially inhibited by L
      selectin-blocking antibody or a previously described sLe(x) mimetic (CGP69669A).
      Together these data suggest that leukocytes can continue to roll in the absence
      of optimal P-selectin/PSGL-1 interaction using an alternative mechanism that
      involves P-selectin-, L-selectin-, and sLe(x)-bearing ligands.

PMID- 15743806
TI  - Bruton's tyrosine kinase regulates immunoglobulin promoter activation in
      association with the transcription factor Bright.
AB  - Bright (B-cell regulator of immunoglobulin heavy chain transcription) binding to
      immunoglobulin heavy chain loci after B-cell activation is associated with
      increased heavy chain transcription. Our earlier reports demonstrated that Bright
      coimmunoprecipitates with Bruton's tyrosine kinase (Btk) and that these proteins
      associate in a DNA-binding complex in primary B cells. B cells from
      immunodeficient mice with a mutation in Btk failed to produce stable Bright DNA
      binding complexes. In order to determine if Btk is important for Bright function,
      a transcription activation assay was established and analyzed using real-time PCR
      technology. Cells lacking both Bright and Btk were transfected with Bright and/or
      Btk along with an immunoglobulin heavy chain reporter construct. Immunoglobulin
      gene transcription was enhanced when Bright and Btk were coexpressed. In
      contrast, neither Bright nor Btk alone led to activation of heavy chain
      transcription. Furthermore, Bright function required both Btk kinase activity and
      sequences within the pleckstrin homology domain of Btk. Bright was not
      appreciably phosphorylated by Btk; however, a third tyrosine-phosphorylated
      protein coprecipitated with Bright. Thus, the ability of Bright to enhance
      immunoglobulin transcription critically requires functional Btk.

PMID- 15743807
TI  - High-resolution genome-wide mapping of transposon integration in mammals.
AB  - The Sleeping Beauty (SB) transposon is an emerging tool for transgenesis, gene
      discovery, and therapeutic gene delivery in mammals. Here we studied 1,336 SB
      insertions in primary and cultured mammalian cells in order to better understand
      its target site preferences. We report that, although widely distributed, SB
      integration recurrently targets certain genomic regions and shows a small but
      significant bias toward genes and their upstream regulatory sequences. Compared
      to those of most integrating viruses, however, the regional preferences
      associated with SB-mediated integration were much less pronounced and were not
      significantly influenced by transcriptional activity. Insertions were also
      distinctly nonrandom with respect to intergenic sequences, including a strong
      bias toward microsatellite repeats, which are predominantly enriched in noncoding
      DNA. Although we detected a consensus sequence consistent with a twofold dyad
      symmetry at the target site, the most widely used sites did not match this
      consensus. In conjunction with an observed SB integration preference for bent
      DNA, these results suggest that physical properties may be the major determining
      factor in SB target site selection. These findings provide basic insights into
      the transposition process and reveal important distinctions between transposon-
      and virus-based integrating vectors.

PMID- 15743808
TI  - Inhibition of protein synthesis by Y box-binding protein 1 blocks oncogenic cell
      transformation.
AB  - The multifunctional Y box-binding protein 1 (YB-1) is transcriptionally repressed
      by the oncogenic phosphoinositide 3-kinase (PI3K) pathway (with P3K as an
      oncogenic homolog of the catalytic subunit) and, when reexpressed with the
      retroviral vector RCAS, interferes with P3K- and Akt-induced transformation of
      chicken embryo fibroblasts. Retrovirally expressed YB-1 binds to the cap of mRNAs
      and inhibits cap-dependent and cap-independent translation. To determine the
      requirements for the inhibitory role of YB-1 in P3K-induced transformation, we
      conducted a mutational analysis, measuring YB-1-induced interference with
      transformation, subcellular localization, cap binding, mRNA binding,
      homodimerization, and inhibition of translation. The results show that (i)
      interference with transformation requires RNA binding and a C-terminal domain
      that is distinct from the cytoplasmic retention domain, (ii) interference with
      transformation is tightly correlated with inhibition of translation, and (iii)
      masking of mRNAs by YB-1 is not sufficient to block transformation or to inhibit
      translation. We identified a noncanonical nuclear localization signal (NLS) in
      the C-terminal half of YB-1. A mutant lacking the NLS retains its ability to
      interfere with transformation, indicating that a nuclear function is not
      required. These results suggest that YB-1 interferes with P3K-induced
      transformation by a specific inhibition of translation through its RNA-binding
      domain and a region in the C-terminal domain. Potential functions of the C
      terminal region are discussed.

PMID- 15743809
TI  - Genetic and functional interaction of evolutionarily conserved regions of the
      Prp18 protein and the U5 snRNA.
AB  - Both the Prp18 protein and the U5 snRNA function in the second step of pre-mRNA
      splicing. We identified suppressors of mutant prp18 alleles in the gene for the
      U5 snRNA (SNR7). The suppressors' U5 snRNAs have either a U4-to-A or an A8-to-C
      mutation in the evolutionarily invariant loop 1 of U5. Suppression is specific
      for prp18 alleles that encode proteins with mutations in a highly conserved
      region of Prp18 which forms an unstructured loop in crystals of Prp18. The snr7
      suppressors partly restored the pre-mRNA splicing activity that was lost in the
      prp18 mutants. The close functional relationship of Prp18 and U5 is emphasized by
      the finding that two snr7 alleles, U5A and U6A, are dominant synthetic lethal
      with prp18 alleles. Our results support the idea that Prp18 and the U5 snRNA act
      in concert during the second step of pre-mRNA splicing and suggest a model in
      which the conserved loop of Prp18 acts to stabilize the interaction of loop 1 of
      the U5 snRNA with the splicing intermediates.

PMID- 15743810
TI  - Structural and functional characterization of PC2 and RNA polymerase II
      associated subpopulations of metazoan Mediator.
AB  - The coactivator complexes TRAP/SMCC and PC2 represent two forms of Mediator. To
      further understand the implications of the heterogeneity of the cellular Mediator
      populations for regulation of RNA polymerase II (Pol II) transcription, we used a
      combination of affinity and conventional chromatographic methods. Our analysis
      revealed a spectrum of complexes, including some containing significant
      proportions of Pol II. Interestingly, the subunit composition of the Pol II
      associated Mediator population resembled that of PC2 more closely than that of
      the larger TRAP/SMCC complex. In in vitro transcription assays reconstituted from
      homogeneous preparations of general transcription factors, Mediator-associated
      Pol II displayed a greater specific activity (relative to that of standard Pol
      II) in activator-independent (basal) transcription in addition to the previously
      described effects of Mediator on activator-dependent transcription. Purified PC2
      complex also stimulated basal activity under these conditions. Immobilized
      template assays in which activator-recruited preinitiation complexes were allowed
      to undergo one cycle of transcription revealed partial disruption of Mediator
      that resulted in a PC2-like complex being retained in the scaffold. This result
      implies that PC2 could originate as a result of a normal cellular process. Our
      results are thus consistent with a dynamic nature of the Mediator complex and
      further extend the functional similarities between Saccharomyces cerevisiae and
      metazoan Mediator complexes.

PMID- 15743811
TI  - TRAF2 plays a key, nonredundant role in LIGHT-lymphotoxin beta receptor
      signaling.
AB  - LIGHT is a member of the tumor necrosis factor (TNF) superfamily, and its
      function is mediated by at least two receptors, including lymphotoxin beta
      receptor (LTbetaR) and herpes simplex virus entry mediator. However, the
      molecular mechanism of LIGHT signaling mediated by LTbetaR has not been clearly
      defined. In this report, we demonstrate that TRAF2 is critical for LIGHT- and
      LTbetaR-mediated activation of both the transcription factor NF-kappaB and the
      mitogen-activated protein kinase JNK. In HeLa cells, LIGHT induces NF-kappaB and
      JNK activation, which can be blocked by the dominant negative mutant of TRAF2. In
      these cells, LIGHT causes the recruitment of TRAF2, TRAF3, and IkappaB kinase
      into the LTbetaR complex. Importantly, while both NF-kappaB and JNK are activated
      by LIGHT in wild-type mouse embryonic fibroblasts, no activation of either of
      these two pathways is observed in TRAF2 null fibroblasts. However, LIGHT-induced
      NF-kappaB and JNK activation can be restored by ectopic expression of TRAF2 in
      TRAF2-/- cells. Interestingly, in contrast to TNF signaling, the activation of
      both NF-kappaB and JNK by LIGHT was normal in RIP-/- and TRAF5-/- cells. Taken
      together, our data demonstrate that TRAF2, an important effector molecule of TNF
      signaling, plays a critical, nonredundant role in LIGHT-LTbetaR signaling.

PMID- 15743812
TI  - Combined global localization analysis and transcriptome data identify genes that
      are directly coregulated by Adr1 and Cat8.
AB  - In Saccharomyces cerevisiae, glucose depletion causes a profound alteration in
      metabolism, mediated in part by global transcriptional changes. Many of the
      transcription factors that regulate these changes act combinatorially. We have
      analyzed combinatorial regulation by Adr1 and Cat8, two transcription factors
      that act during glucose depletion, by combining genome-wide expression and genome
      wide binding data. We identified 32 genes that are directly activated by Adr1, 28
      genes that are directly activated by Cat8, and 14 genes that are directly
      regulated by both. Our analysis also uncovered promoters that Adr1 binds but does
      not regulate and promoters that are indirectly regulated by Cat8, stressing the
      advantage of combining global expression and global localization analysis to find
      directly regulated targets. At most of the coregulated promoters, the in vivo
      binding of one factor is independent of the other, but Adr1 is required for
      optimal Cat8 binding at two promoters with a poor match to the Cat8 binding
      consensus. In addition, Cat8 is required for Adr1 binding at promoters where Adr1
      is not required for transcription. These data provide a comprehensive analysis of
      the direct, indirect, and combinatorial requirements for these two global
      transcription factors.

PMID- 15743813
TI  - Transcription factor interactions and chromatin modifications associated with p53
      mediated, developmental repression of the alpha-fetoprotein gene.
AB  - We performed chromatin immunoprecipitation (ChIP) analyses of developmentally
      staged solid tissues isolated from wild-type and p53-null mice to determine
      specific histone N-terminal modifications, histone-modifying proteins, and
      transcription factor interactions at the developmental repressor region (-850)
      and core promoter of the hepatic tumor marker alpha-fetoprotein (AFP) gene. Both
      repression of AFP during liver development and silencing in the brain, where AFP
      is never expressed, are associated with dimethylation of histone H3 lysine 9
      (DiMetH3K9) and the presence of heterochromatin protein 1 (HP1). These
      heterochromatic markers remain localized to AFP during developmental repression
      but spread to the upstream albumin gene during silencing. Developmentally
      regulated decreases in levels of acetylated H3 (AcH3K9) and H4 (AcH4) and of di-
      and trimethylated H3K4 (DiMetH3K4 and TriMetH3K4) occur at both the core promoter
      and distal repressor regions of AFP. Hepatic expression of AFP correlates with
      FoxA interaction at the repressor region and the binding of RNA polymerase II and
      TATA-binding protein to the core promoter. p53 acts as a developmental repressor
      of AFP in the liver by binding to chromatin, excluding FoxA interaction and
      targeting mSin3A/HDAC1 to the distal repressor region. p53-null mice exhibit
      developmentally delayed AFP repression, concomitant with acetylation of H3K9,
      methylation of H3K4, and loss of DiMetH3K9, mSin3A/HDAC1, and HP1 interactions.

PMID- 15743814
TI  - Human telomeres maintain their overhang length at senescence.
AB  - Normal human cells in culture enter replicative senescence after a finite number
      of population doublings. The exact molecular mechanisms triggering the growth
      arrest are poorly understood. A recent report on the disappearance of the G-rich
      3' telomeric overhang in senescent cells led to the hypothesis that loss of the
      3' G-rich overhang is the molecular signal that triggers senescence. Here, we
      describe a quantitative assay to measure the length of the G-rich 3' telomeric
      overhangs from cultured cells. Using both this assay and the conventional
      nondenaturing hybridization assay for measuring G-rich overhangs, we show that
      normal human fibroblasts can maintain their overhangs at senescence. Furthermore,
      cells do not lose their overhangs when they bypass senescence after the
      inactivation of p53 and Rb. We thus conclude that a global reduction in overhang
      length is not the molecular signal that triggers replicative senescence.

PMID- 15743815
TI  - Mechanism of efficient and accurate nucleotide incorporation opposite 7,8-dihydro
      8-oxoguanine by Saccharomyces cerevisiae DNA polymerase eta.
AB  - Most DNA polymerases incorporate nucleotides opposite template 7,8-dihydro-8
      oxoguanine (8-oxoG) lesions with reduced efficiency and accuracy. DNA polymerase
      (Pol) eta, which catalyzes the error-free replication of template thymine-thymine
      (TT) dimers, has the unique ability to accurately and efficiently incorporate
      nucleotides opposite 8-oxoG templates. Here we have used pre-steady-state
      kinetics to examine the mechanisms of correct and incorrect nucleotide
      incorporation opposite G and 8-oxoG by Saccharomyces cerevisiae Pol eta. We found
      that Pol eta binds the incoming correct dCTP opposite both G and 8-oxoG with
      similar affinities, and it incorporates the correct nucleotide bound opposite
      both G and 8-oxoG with similar rates. While Pol eta incorporates an incorrect A
      opposite 8-oxoG with lower efficiency than it incorporates a correct C, it does
      incorporate A more efficiently opposite 8-oxoG than opposite G. This is mainly
      due to greater binding affinity for the incorrect incoming dATP opposite 8-oxoG.
      Overall, these results show that Pol eta replicates through 8-oxoG without any
      barriers introduced by the presence of the lesion.

PMID- 15743816
TI  - Interaction with the SH3 domain protein Bem1 regulates signaling by the
      Saccharomyces cerevisiae p21-activated kinase Ste20.
AB  - The Saccharomyces cerevisiae PAK (p21-activated kinase) family kinase Ste20
      functions in several signal transduction pathways, including pheromone response,
      filamentous growth, and hyperosmotic resistance. The GTPase Cdc42 localizes and
      activates Ste20 by binding to an autoinhibitory motif within Ste20 called the
      CRIB domain. Another factor that functions with Ste20 and Cdc42 is the protein
      Bem1. Bem1 has two SH3 domains, but target ligands for these domains have not
      been described. Here we identify an evolutionarily conserved binding site for
      Bem1 between the CRIB and kinase domains of Ste20. Mutation of tandem proline
      rich (PxxP) motifs in this region disrupts Bem1 binding, suggesting that it
      serves as a ligand for a Bem1 SH3 domain. These PxxP motif mutations affect
      signaling additively with CRIB domain mutations, indicating that Bem1 and Cdc42
      make separable contributions to Ste20 function, which cooperate to promote
      optimal signaling. This PxxP region also binds another SH3 domain protein, Nbp2,
      but analysis of bem1Delta versus nbp2Delta strains shows that the signaling
      defects of PxxP mutants result from impaired binding to Bem1 rather than from
      impaired binding to Nbp2. Finally, the PxxP mutations also reduce signaling by
      constitutively active Ste20, suggesting that postactivation functions of PAKs can
      be promoted by SH3 domain proteins, possibly by colocalizing PAKs with their
      substrates. The overall results also illustrate how the final signaling function
      of a protein can be governed by combinatorial addition of multiple, independent
      protein-protein interaction modules.

PMID- 15743817
TI  - Congenital semilunar valvulogenesis defect in mice deficient in phospholipase C
      epsilon.
AB  - Phospholipase Cepsilon is a novel class of phosphoinositide-specific
      phospholipase C, identified as a downstream effector of Ras and Rap small
      GTPases. We report here the first genetic analysis of its physiological function
      with mice whose phospholipase Cepsilon is catalytically inactivated by gene
      targeting. The hearts of mice homozygous for the targeted allele develop
      congenital malformations of both the aortic and pulmonary valves, which cause a
      moderate to severe degree of regurgitation with mild stenosis and result in
      ventricular dilation. The malformation involves marked thickening of the valve
      leaflets, which seems to be caused by a defect in valve remodeling at the late
      stages of semilunar valvulogenesis. This phenotype has a remarkable resemblance
      to that of mice carrying an attenuated epidermal growth factor receptor or
      deficient in heparin-binding epidermal growth factor-like growth factor.
      Smad1/5/8, which is implicated in proliferation of the valve cells downstream of
      bone morphogenetic protein, shows aberrant activation at the margin of the
      developing semilunar valve tissues in embryos deficient in phospholipase
      Cepsilon. These results suggest a crucial role of phospholipase Cepsilon
      downstream of the epidermal growth factor receptor in controlling semilunar
      valvulogenesis through inhibition of bone morphogenetic protein signaling.

PMID- 15743818
TI  - BAF57 governs androgen receptor action and androgen-dependent proliferation
      through SWI/SNF.
AB  - Androgen receptor (AR) activity is required for prostate cancer development and
      progression. Thus, there is a major impetus to understand the regulation of AR
      action. We and others have previously shown that AR transactivation potential is
      dependent on the presence of an active SWI/SNF chromatin remodeling complex.
      However, the mechanisms underlying SWI/SNF regulation of the AR remained
      unsolved. We show here that the BAF57 subunit, an accessory component of the
      remodeling complex, is a critical regulator of AR function. We show that BAF57 is
      expressed in the luminal epithelia of the prostate and is required for AR
      dependent transactivation in prostatic adenocarcinoma cells. Our data reveal that
      BAF57 can directly bind to the AR and is recruited to endogenous AR targets upon
      ligand activation. Loss of BAF57 or inhibition of BAF57 function severely
      compromised AR activity, as observed with both exogenous and endogenous AR
      targets. Rescue of BAF57 function restored AR activity, thus demonstrating a
      specific requirement of BAF57 for AR activity. This action of BAF57 proved to be
      dependent on SWI/SNF ATPase function. BAF57 has previously been implicated in
      nuclear receptor coactivator function, and we show that, although BAF57
      facilitated coactivator activity, only a selected subset required BAF57 for
      coactivator function. Lastly, we demonstrate that both BAF57 and BRM are required
      for the proliferation of AR-dependent prostatic adenocarcinoma cells. In summary,
      these findings identify BAF57 as a critical modulator of the AR that is capable
      of altering AR activity, coactivator function, and AR-dependent proliferation.

PMID- 15743819
TI  - Novel and essential subunits in the 300-kilodalton nuclear cap binding complex of
      Trypanosoma brucei.
AB  - One of the unique aspects of RNA processing in trypanosomatid protozoa is the
      presence of a cap 4 structure (m7Gpppm2(6)AmpAmpCmpm3Um) at the 5' end of all
      mRNAs. The cap 4 becomes part of the mRNA through trans-splicing of a 39
      nucleotide-long sequence donated by the spliced leader RNA. Although the cap 4
      modifications are required for trans-splicing to occur, the underlying mechanism
      remains to be determined. We now describe an unconventional nuclear cap binding
      complex (CBC) in Trypanosoma brucei with an apparent molecular mass of 300 kDa
      and consisting of five protein components: the known CBC subunits CBP20 and
      importin-alpha and three novel proteins that are only present in organisms
      featuring a cap 4 structure and trans-splicing. Competitive binding studies are
      consistent with a specific interaction between the CBC and the cap 4 structure.
      Downregulation of several individual components of the T. brucei CBC by RNA
      interference demonstrated an essential function at an early step in trans
      splicing. Thus, our studies are consistent with the CBC providing a mechanistic
      link between cap 4 modifications and trans-splicing.

PMID- 15743820
TI  - Removal of C-terminal SRC kinase from the immune synapse by a new binding
      protein.
AB  - The Csk tyrosine kinase negatively regulates the Src family kinases Lck and Fyn
      in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk
      from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk
      becomes associated with an approximately 72-kDa tyrosine-phosphorylated protein,
      which we identify here as G3BP, a phosphoprotein reported to bind the SH3 domain
      of Ras GTPase-activating protein. G3BP reduced the ability of Csk to
      phosphorylate Lck at Y505 by decreasing the amount of Csk in lipid rafts. As a
      consequence, G3BP augmented T-cell activation as measured by interleukin-2 gene
      activation. Conversely, elimination of endogenous G3BP by RNA interference
      increased Lck Y505 phosphorylation and reduced TCR signaling. In antigen-specific
      T cells, endogenous G3BP moved into a intracellular location adjacent to the
      immune synapse, but deeper inside the cell, upon antigen recognition. Csk
      colocalization with G3BP occurred in this "parasynaptic" location. We conclude
      that G3BP is a new player in T-cell-antigen receptor signaling and acts to reduce
      the amount of Csk in the immune synapse.

PMID- 15743822
TI  - Performance of genomic bordering elements at predefined genomic loci.
AB  - Eukaryotic DNA is organized into chromatin domains that regulate gene expression
      and chromosome behavior. Insulators and/or scaffold-matrix attachment regions
      (S/MARs) mark the boundaries of these chromatin domains where they delimit
      enhancing and silencing effects from the outside. By recombinase-mediated
      cassette exchange (RMCE), we were able to compare these two types of bordering
      elements at a number of predefined genomic loci. Flanking an expression vector
      with either S/MARs or two copies of the non-S/MAR chicken hypersensitive site 4
      insulator demonstrates that while these borders confer related expression
      characteristics at most loci, their effect on chromatin organization is clearly
      distinct. Our results suggest that the activity of bordering elements is most
      pronounced for the abundant class of loci with a low but negligible expression
      potential in the case of highly expressed sites. By the RMCE procedure, we
      demonstrate that expression parameters are not due to a potential targeting
      action of bordering elements, in the sense that a linked transgene is directed
      into a special class of loci. Instead, we can relate the observed transcriptional
      augmentation phenomena to their function as genomic insulators.

PMID- 15743821
TI  - PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition
      of myocyte enhancer factor 2C.
AB  - Histone deacetylase 4 (HDAC4) negatively regulates skeletal myogenesis by
      associating with the myocyte enhancer factor 2 (MEF2) transcription factors. Our
      data indicate that the gene PC4 (interferon-related developmental regulator 1
      [IFRD1], Tis7), which we have previously shown to be required for myoblast
      differentiation, is both induced by MyoD and potentiates the transcriptional
      activity of MyoD, thus revealing a positive regulatory loop between these
      molecules. Enhancement by PC4 of MyoD-dependent activation of muscle gene
      promoters occurs selectively through MEF2 binding sites. Furthermore, PC4
      localizes in the nucleus of differentiating myoblasts, associates with MEF2C, and
      is able to counteract the HDAC4-mediated inhibition of MEF2C. This latter action
      can be explained by the observed ability of PC4 to dose dependently displace
      HDAC4 from MEF2C. Consistently, we have observed that (i) the region of PC4 that
      binds MEF2C is sufficient to counteract the inhibition by HDAC4; (ii) PC4,
      although able to bind HDAC4, does not inhibit the enzymatic activity of HDAC4;
      and (iii) PC4 overcomes the inhibition mediated by the amino-terminal domain of
      HDAC4, which associates with MEF2C but not with PC4. Together, our findings
      strongly suggest that PC4 acts as a coactivator of MyoD and MEF2C by removing the
      inhibitory effect of HDAC4, thus exerting a pivotal function during myogenesis.

PMID- 15743823
TI  - Association with class IIa histone deacetylases upregulates the sumoylation of
      MEF2 transcription factors.
AB  - The myocyte enhancer factor-2 (MEF2) family of transcription factors plays an
      important role in regulating cellular programs like muscle differentiation,
      neuronal survival, and T-cell apoptosis. Multisite phosphorylation is known to
      control the transcriptional activity of MEF2 proteins, but it is unclear whether
      other modifications are involved. Here, we report that human MEF2D, as well as
      MEF2C, is modified by SUMO2 and SUMO3 at a motif highly conserved among MEF2
      proteins from diverse organisms. This motif is located within the C-terminal
      transcriptional activation domain, and its sumoylation inhibits transcription. As
      a transcriptional corepressor of MEF2, histone deacetylase 4 (HDAC4) potentiates
      sumoylation. This potentiation is dependent on the N-terminal region but not the
      C-terminal deacetylase domain of HDAC4 and is inhibited by the sumoylation of
      HDAC4 itself. Moreover, HDAC5, HDAC7, and an HDAC9 isoform also stimulate
      sumoylation of MEF2. Opposing the action of class IIa deacetylases, the SUMO
      protease SENP3 reverses the sumoylation to augment the transcriptional and
      myogenic activities of MEF2. Similarly, the calcium/calmodulin-dependent kinases
      [corrected] and extracellular signal-regulated kinase 5 signaling pathways
      negatively regulate the sumoylation. These results thus identify sumoylation as a
      novel regulatory mechanism for MEF2 and suggest that this modification interplays
      with phosphorylation to promote intramolecular signaling for coordinated
      regulation in vivo.

PMID- 15743824
TI  - Inactivation of the pre-mRNA cleavage and polyadenylation factor Pfs2 in fission
      yeast causes lethal cell cycle defects.
AB  - Faithful chromosome segregation is fundamentally important for the maintenance of
      genome integrity and ploidy. By isolating conditional mutants defective in
      chromosome segregation in the fission yeast Schizosaccharomyces pombe, we
      identified a role for the essential gene pfs2 in chromosome dynamics. In the
      absence of functional Pfs2, chromosomal attachment to the mitotic spindle was
      defective, with consequent chromosome missegregation. Under these circumstances,
      multiple intracellular foci of spindle checkpoint proteins Bub1 and Mad2 were
      seen, and deletion of bub1 exacerbated the mitotic defects and the loss of cell
      viability that resulted from the loss of pfs2 function. Progression from G1 into
      S phase following release from nitrogen starvation also required pfs2+ function.
      The product of the orthologous Saccharomyces cerevisiae gene PFS2 is a component
      of a multiprotein complex required for 3'-end cleavage and polyadenylation of pre
      mRNAs and, in keeping with the conservation of this essential function, an S.
      pombe pfs2 mutant was defective in mRNA 3'-end processing. Mutations in pfs2 were
      suppressed by overexpression of the putative mRNA 3'-end cleavage factor Cft1.
      These data suggest unexpected links between mRNA 3'-end processing and chromosome
      replication and segregation.

PMID- 15743825
TI  - DNA interstrand cross-link repair in the Saccharomyces cerevisiae cell cycle:
      overlapping roles for PSO2 (SNM1) with MutS factors and EXO1 during S phase.
AB  - Pso2/Snm1 is a member of the beta-CASP metallo-beta-lactamase family of proteins
      that include the V(D)J recombination factor Artemis. Saccharomyces cerevisiae
      pso2 mutants are specifically sensitive to agents that induce DNA interstrand
      cross-links (ICLs). Here we establish a novel overlapping function for PSO2 with
      MutS mismatch repair factors and the 5'-3' exonuclease Exo1 in the repair of DNA
      ICLs, which is confined to S phase. Our data demonstrate a requirement for NER
      and Pso2, or Exo1 and MutS factors, in the processing of ICLs, and this is
      required prior to the repair of ICL-induced DNA double-strand breaks (DSBs) that
      form during replication. Using a chromosomally integrated inverted-repeat
      substrate, we also show that loss of both pso2 and exo1/msh2 reduces spontaneous
      homologous recombination rates. Therefore, PSO2, EXO1, and MSH2 also appear to
      have overlapping roles in the processing of some forms of endogenous DNA damage
      that occur at an irreversibly collapsed replication fork. Significantly, our
      analysis of ICL repair in cells synchronized for each cell cycle phase has
      revealed that homologous recombination does not play a major role in the direct
      repair of ICLs, even in G2, when a suitable template is readily available.
      Rather, we propose that recombination is primarily involved in the repair of DSBs
      that arise from the collapse of replication forks at ICLs. These findings have
      led to considerable clarification of the complex genetic relationship between
      various ICL repair pathways.

PMID- 15743826
TI  - Inactivation of the Sema5a gene results in embryonic lethality and defective
      remodeling of the cranial vascular system.
AB  - The semaphorins are a large family of proteins involved in the patterning of both
      the vascular and the nervous systems. In order to analyze the function of the
      membrane-bound semaphorin 5A (Sema5A), we generated mice homozygous for a null
      mutation in the Sema5a gene. Homozygous null mutants die between embryonic
      development days 11.5 (E11.5) and E12.5, indicating an essential role of Sema5A
      during embryonic development. Mutant embryos did not show any morphological
      defects that could account for the lethality of the mutation. A detailed analysis
      of the vascular system uncovered a role of Sema5A in the remodeling of the
      cranial blood vessels. In Sema5A null mutants, the complexity of the
      hierarchically organized branches of the cranial cardinal veins was decreased.
      Our results represent the first genetic analysis of the function of a class 5
      semaphorin during embryonic development and identify a role of Sema5A in the
      regional patterning of the vasculature.

PMID- 15743827
TI  - Acute tumor necrosis factor alpha signaling via NADPH oxidase in microvascular
      endothelial cells: role of p47phox phosphorylation and binding to TRAF4.
AB  - Tumor necrosis factor alpha (TNF-alpha) receptor-associated factors (TRAFs) play
      important roles in TNF-alpha signaling by interacting with downstream signaling
      molecules, e.g., mitogen-activated protein kinases (MAPKs). However, TNF-alpha
      also signals through reactive oxygen species (ROS)-dependent pathways. The
      interrelationship between these pathways is unclear; however, a recent study
      suggested that TRAF4 could bind to the NADPH oxidase subunit p47phox. Here, we
      investigated the potential interaction between p47phox phosphorylation and TRAF4
      binding and their relative roles in acute TNF-alpha signaling. Exposure of human
      microvascular endothelial cells (HMEC-1) to TNF-alpha (100 U/ml; 1 to 60 min)
      induced rapid (within 5 min) p47phox phosphorylation. This was paralleled by a
      2.7- +/- 0.5-fold increase in p47phox-TRAF4 association, membrane translocation
      of p47phox-TRAF4, a 2.3- +/- 0.4-fold increase in p47phox-p22phox complex
      formation, and a 3.2- +/- 0.2-fold increase in NADPH-dependent O2- production
      (all P < 0.05). TRAF4-p47phox binding was accompanied by a progressive increase
      in extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38(MAPK)
      activation, which was inhibited by an O2- scavenger, tiron. TRAF4 predominantly
      bound the phosphorylated form of p47phox, in a protein kinase C-dependent
      process. Knockdown of TRAF4 expression using siRNA had no effect on p47phox
      phosphorylation or binding to p22phox but inhibited TNF-alpha-induced ERK1/2
      activation. In coronary microvascular EC from p47phox-/- mice, TNF-alpha-induced
      NADPH oxidase activation, ERK1/2 activation, and cell surface intercellular
      adhesion molecule 1 (ICAM-1) expression were all inhibited. Thus, both p47phox
      phosphorylation and TRAF4 are required for acute TNF-alpha signaling. The
      increased binding between p47phox and TRAF4 that occurs after p47phox
      phosphorylation could serve to spatially confine ROS generation from NADPH
      oxidase and subsequent MAPK activation and cell surface ICAM-1 expression in EC.

PMID- 15743828
TI  - RNA interference (RNAi)-dependent and RNAi-independent association of the Chp1
      chromodomain protein with distinct heterochromatic loci in fission yeast.
AB  - The establishment of centromeric heterochromatin in the fission yeast
      Schizosaccharomyces pombe is dependent on the RNA interference (RNAi) pathway.
      Dicer cleaves centromeric transcripts to produce short interfering RNAs (siRNAs)
      that actively recruit components of heterochromatin to centromeres. Both
      centromeric siRNAs and the heterochromatin component Chp1 are components of the
      RITS (RNA-induced initiation of transcriptional gene silencing) complex, and the
      association of RITS with centromeres is linked to Dicer activity. In turn,
      centromeric binding of RITS promotes Clr4-mediated methylation of histone H3
      lysine 9 (K9), recruitment of Swi6, and formation of heterochromatin. Similar to
      centromeres, the mating type locus (Mat) is coated in K9-methylated histone H3
      and is bound by Swi6. Here we report that Chp1 associates with the mating type
      locus and telomeres and that Chp1 localization to heterochromatin depends on its
      chromodomain and the C-terminal domain of the protein. Another protein component
      of the RITS complex, Tas3, also binds to Mat and telomeres. Tas3 interacts with
      Chp1 through the C-terminal domain of Chp1, and this interaction is necessary for
      Tas3 stability. Interestingly, in cells lacking the Argonaute (Ago1) protein
      component of the RITS complex, or lacking Dicer (and hence siRNAs), Chp1 and Tas3
      can still bind to noncentromeric loci, although their association with
      centromeres is lost. Thus, Chp1 and Tas3 exist as an Ago1-independent subcomplex
      that associates with noncentromeric heterochromatin independently of the RNAi
      pathway.

PMID- 15743829
TI  - Phosphoinositide-dependent phosphorylation of PDK1 regulates nuclear
      translocation.
AB  - 3-phosphoinositide-dependent kinase 1 (PDK1) phosphorylates the activation loop
      of a number of protein serine/threonine kinases of the AGC kinase superfamily,
      including protein kinase B (PKB; also called Akt), serum and glucocorticoid
      induced kinase, protein kinase C isoforms, and the p70 ribosomal S6 kinase. PDK1
      contains a carboxyl-terminal pleckstrin homology domain, which targets
      phosphoinositide lipids at the plasma membrane and is central to the activation
      of PKB. However, PDK1 subcellular trafficking to other compartments is not well
      understood. We monitored the posttranslational modifications of PDK1 following
      insulin-like growth factor 1 stimulation. PDK1 underwent rapid and transient
      phosphorylation on S396, which was dependent upon plasma membrane localization.
      Phosphorylation of S396 was necessary for nuclear shuttling of PDK1, possibly
      through its influence on an adjacent nuclear export sequence. Thus, mitogen
      stimulated phosphorylation of PDK1 provides a means for directed PDK1 subcellular
      trafficking, with potential implications for PDK1 signaling.

PMID- 15743830
TI  - Activation of hematopoietic progenitor kinase 1 involves relocation,
      autophosphorylation, and transphosphorylation by protein kinase D1.
AB  - Adaptive immune signaling can be coupled to stress-activated protein kinase
      (SAPK)/c-Jun N-terminal kinase (JNK) and NF-kappaB activation by the
      hematopoietic progenitor kinase 1 (HPK1), a mammalian hematopoiesis-specific
      Ste20 kinase. To gain insight into the regulation of leukocyte signal
      transduction, we investigated the molecular details of HPK1 activation. Here we
      demonstrate the capacity of the Src family kinase Lck and the SLP-76 family
      adaptor protein Clnk (cytokine-dependent hematopoietic cell linker) to induce
      HPK1 tyrosine phosphorylation and relocation to the plasma membrane, which in
      lymphocytes results in recruitment of HPK1 to the contact site of antigen
      presenting cell (APC)-T-cell conjugates. Relocation and clustering of HPK1 cause
      its enzymatic activation, which is accompanied by phosphorylation of regulatory
      sites in the HPK1 kinase activation loop. We show that full activation of HPK1 is
      dependent on autophosphorylation of threonine 165 and phosphorylation of serine
      171, which is a target site for protein kinase D (PKD) in vitro. Upon T-cell
      receptor stimulation, PKD robustly augments HPK1 kinase activity in Jurkat T
      cells and enhances HPK1-driven SAPK/JNK and NF-kappaB activation; conversely,
      antisense down-regulation of PKD results in reduced HPK1 activity. Thus,
      activation of major lymphocyte signaling pathways via HPK1 involves (i)
      relocation, (ii) autophosphorylation, and (iii) transphosphorylation of HPK1 by
      PKD.

PMID- 15743831
TI  - The NF2 tumor suppressor gene product, merlin, inhibits cell proliferation and
      cell cycle progression by repressing cyclin D1 expression.
AB  - Inactivation of the NF2 tumor suppressor gene has been observed in certain benign
      and malignant tumors. Recent studies have demonstrated that merlin, the product
      of the NF2 gene, is regulated by Rac/PAK signaling. However, the mechanism by
      which merlin acts as a tumor suppressor has remained obscure. In this report, we
      show that adenovirus-mediated expression of merlin in NF2-deficient tumor cells
      inhibits cell proliferation and arrests cells at G1 phase, concomitant with
      decreased expression of cyclin D1, inhibition of CDK4 activity, and
      dephosphorylation of pRB. The effect of merlin on cell cycle progression was
      partially overridden by ectopic expression of cyclin D1. RNA interference
      experiments showed that silencing of the endogenous NF2 gene results in
      upregulation of cyclin D1 and S-phase entry. Furthermore, PAK1-stimulated cyclin
      D1 promoter activity was repressed by cotransfection of NF2, and PAK activity was
      inhibited by expression of merlin. Interestingly, the S518A mutant form of
      merlin, which is refractory to phosphorylation by PAK, was more efficient than
      the wild-type protein in inhibiting cell cycle progression and in repressing
      cyclin D1 promoter activity. Collectively, our data indicate that merlin exerts
      its antiproliferative effect, at least in part, via repression of PAK-induced
      cyclin D1 expression, suggesting a unifying mechanism by which merlin
      inactivation might contribute to the overgrowth seen in both noninvasive and
      malignant tumors.

PMID- 15743832
TI  - The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis.
AB  - The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent
      target of chromosome translocations in human leukemia and specific solid tumors.
      Here we report that TEL2 augments the proliferation and survival of normal mouse
      B cells and dramatically accelerates lymphoma development in Emu-Myc transgenic
      mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu
      Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass
      this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human
      sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic
      leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or
      MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to
      cooperate in provoking a cadre of human B-cell malignancies.

PMID- 15743833
TI  - Ligand-specific dynamics of the progesterone receptor in living cells and during
      chromatin remodeling in vitro.
AB  - Progesterone receptor (PR), a member of the nuclear receptor superfamily, is a
      key regulator of several processes in reproductive function. We have studied the
      dynamics of the interaction of PR with a natural target promoter in living cells
      through the use of fluorescence recovery after photobleaching (FRAP) analysis and
      also have characterized the dynamics of the interaction of PR with the mouse
      mammary tumor virus (MMTV) promoter reconstituted into chromatin in vitro. In
      photobleaching experiments, PR in the presence of the agonist R5020 exhibits
      rapid exchange with the MMTV promoter in living cells. Two PR antagonists, RU486
      and ZK98299, have opposite effects on receptor dynamics in vivo. In the presence
      of RU486, PR binds to the promoter and is exchanged more slowly than the agonist
      activated receptor. In contrast, PR bound to ZK98299 is not localized to the
      promoter and exhibits higher mobility in the nucleoplasm than the agonist-bound
      receptor. Significantly, PR bound to R5020 or RU486 can recruit the SWI/SNF
      chromatin remodeling complex to the promoter, but PR activated with ZK98299
      cannot. Furthermore, we found ligand-specific active displacement of PR from the
      MMTV promoter during chromatin remodeling in vitro and conclude that the
      interaction of PR with chromatin is highly dynamic both in vivo and in vitro. We
      propose that factor displacement during chromatin remodeling is an important
      component of receptor mobility and that ligand-specific interactions with
      remodeling complexes can strongly influence receptor nuclear dynamics and rates
      of exchange with chromatin in living cells.

PMID- 15743834
TI  - p21WAF1/CIP1 selectively controls the transcriptional activity of estrogen
      receptor alpha.
AB  - Estrogen receptors (ER) are ligand-dependent transcription factors that regulate
      growth, differentiation, and maintenance of cellular functions in a wide variety
      of tissues. We report here that p21WAF1/CIP1, a cyclin-dependent kinase (Cdk)
      inhibitor, cooperates with CBP to regulate the ERalpha-mediated transcription of
      endogenous target genes in a promoter-specific manner. The estrogen-induced
      expression of the progesterone receptor and WISP-2 mRNA transcripts in MCF-7
      cells was enhanced by p21WAF1/CIP1, whereas that of the cyclin D1 mRNA was
      reduced and the pS2 mRNA was not affected. Chromatin immunoprecipitation assays
      revealed that p21WAF1/CIP1 was recruited simultaneously with ERalpha and CBP to
      the endogenous progesterone receptor gene promoter in an estrogen-dependent
      manner. Experiments in which the p21WAF1/CIP1 protein was knocked down by RNA
      interference showed that the induction of the expression of the gene encoding the
      progesterone receptor required p21WAF1/CIP1, in contrast with that of the cyclin
      D1 and pS2 genes. p21WAF1/CIP1 induced not only cell cycle arrest in breast
      cancer cells but also milk fat globule protein and lipid droplets, indicators of
      the differentiated phenotype, as well as cell flattening and increase of the
      volume of the cytoplasm. These results indicate that p21WAF1/CIP1, in addition to
      its Cdk-regulatory role, behaves as a transcriptional coactivator in a gene
      specific manner implicated in cell differentiation.

PMID- 15743835
TI  - The exon 8-containing prosaposin gene splice variant is dispensable for mouse
      development, lysosomal function, and secretion.
AB  - Prosaposin is a multifunctional protein with diverse functions. Intracellularly,
      prosaposin is a precursor of four sphingolipid activator proteins, saposins A to
      D, which are required for hydrolysis of sphingolipids by several lysosomal
      exohydrolases. Secreted prosaposin has been implicated as a neurotrophic,
      myelinotrophic, and myotrophic factor as well as a spermatogenic factor. It has
      also been implicated in fertilization. The human and the mouse prosaposin gene
      has a 9-bp exon (exon 8) that is alternatively spliced, resulting in an isoform
      with three extra amino acids, Gln-Asp-Gln, within the saposin B domain.
      Alternative splicing in the prosaposin gene is conserved from fish to humans,
      tissue specific, and regulated in the brain during development and nerve
      regeneration-degeneration processes. To elucidate the physiological role of
      alternative splicing, we have generated a mouse lacking exon 8 by homologous
      recombination. The exon 8 prosaposin mutant mice are healthy and fertile with no
      obvious phenotype. No changes were detected in prosaposin secretion or in
      accumulation and metabolism of gangliosides, sulfatides, neutral
      glycosphingolipids, neutral phospholipids, other neutral lipids, and ceramide.
      These data strongly indicate that the prosaposin variant containing the exon 8
      encoded three amino acids is dispensable for normal mouse development and
      fertility as well as for prosaposin secretion and its lysosomal function, at
      least in the presence of the prosaposin variant missing the exon 8-encoded three
      amino acids.

PMID- 15743836
TI  - Vascular endothelial growth factor D is dispensable for development of the
      lymphatic system.
AB  - Vascular endothelial growth factor receptor 3 (Vegfr-3) is a tyrosine kinase that
      is expressed on the lymphatic endothelium and that signals for the growth of the
      lymphatic vessels (lymphangiogenesis). Vegf-d, a secreted glycoprotein, is one of
      two known activating ligands for Vegfr-3, the other being Vegf-c. Vegf-d
      stimulates lymphangiogenesis in tissues and tumors; however, its role in
      embryonic development was previously unknown. Here we report the generation and
      analysis of mutant mice deficient for Vegf-d. Vegf-d-deficient mice were healthy
      and fertile, had normal body mass, and displayed no pathologic changes consistent
      with a defect in lymphatic function. The lungs, sites of strong Vegf-d gene
      expression during embryogenesis in wild-type mice, were normal in Vegf-d
      deficient mice with respect to tissue mass and morphology, except that the
      abundance of the lymphatics adjacent to bronchioles was slightly reduced. Dye
      uptake experiments indicated that large lymphatics under the skin were present in
      normal locations and were functional. Smaller dermal lymphatics were similar in
      number, location, and function to those in wild-type controls. The lack of a
      profound lymphatic phenotype in Vegf-d-deficient mice suggests that Vegf-d does
      not play a major role in lymphatic development or that Vegf-c or another, as-yet
      unknown activating Vegfr-3 ligand can compensate for Vegf-d during development.

PMID- 15743837
TI  - Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor
      signaling under stress conditions.
AB  - The cellular stress response (SR) is a phylogenetically conserved protection
      mechanism that involves inhibition of protein synthesis through recruitment of
      translation factors such as eIF4G into insoluble stress granules (SGs) and
      blockade of proinflammatory responses by interruption of the signaling pathway
      from tumor necrosis factor alpha (TNF-alpha) to nuclear factor-kappaB (NF-kappaB)
      activation. However, the link between these two physiological phenomena has not
      been clearly elucidated. Here we report that eIF4GI, which is a scaffold protein
      interacting with many translation factors, interacts with TRAF2, a signaling
      molecule that plays a key role in activation of NF-kappaB through TNF-alpha.
      These two proteins colocalize in SGs during cellular exposure to stress
      conditions. Moreover, TRAF2 is absent from TNFR1 complexes under stress
      conditions even after TNF-alpha treatment. This suggests that stressed cells
      lower their biological activities by sequestration of translation factors and
      TRAF2 into SGs through a protein-protein interaction.

PMID- 15743838
TI  - Novel checkpoint response to genotoxic stress mediated by nucleolin-replication
      protein a complex formation.
AB  - Human replication protein A (RPA), the primary single-stranded DNA-binding
      protein, was previously found to be inhibited after heat shock by complex
      formation with nucleolin. Here we show that nucleolin-RPA complex formation is
      stimulated after genotoxic stresses such as treatment with camptothecin or
      exposure to ionizing radiation. Complex formation in vitro and in vivo requires a
      63-residue glycine-arginine-rich (GAR) domain located at the extreme C terminus
      of nucleolin, with this domain sufficient to inhibit DNA replication in vitro.
      Fluorescence resonance energy transfer studies demonstrate that the nucleolin-RPA
      interaction after stress occurs both in the nucleoplasm and in the nucleolus.
      Expression of the GAR domain or a nucleolin mutant (TM) with a constitutive
      interaction with RPA is sufficient to inhibit entry into S phase. Increasing
      cellular RPA levels by overexpression of the RPA2 subunit minimizes the
      inhibitory effects of nucleolin GAR or TM expression on chromosomal DNA
      replication. The arrest is independent of p53 activation by ATM or ATR and does
      not involve heightened expression of p21. Our data reveal a novel cellular
      mechanism that represses genomic replication in response to genotoxic stress by
      inhibition of an essential DNA replication factor.

PMID- 15743839
TI  - Octamer and Sox elements are required for transcriptional cis regulation of Nanog
      gene expression.
AB  - The pluripotential cell-specific gene Nanog encodes a homeodomain-bearing
      transcription factor required for maintaining the undifferentiated state of stem
      cells. However, the molecular mechanisms that regulate Nanog gene expression are
      largely unknown. To address this important issue, we used luciferase assays to
      monitor the relative activities of deletion fragments from the 5'-flanking region
      of the gene. An adjacent pair of highly conserved Octamer- and Sox-binding sites
      was found to be essential for activating pluripotential state-specific gene
      expression. Furthermore, the 5'-end fragment encompassing the Octamer/Sox element
      was sufficient for inducing the proper expression of a green fluorescent protein
      reporter gene even in human embryonic stem (ES) cells. The potential of OCT4 and
      SOX2 to bind to this element was verified by electrophoretic mobility shift
      assays with extracts from F9 embryonal carcinoma cells and embryonic germ cells
      derived from embryonic day 12.5 embryos. However, in ES cell extracts, a complex
      of OCT4 with an undefined factor preferentially bound to the Octamer/Sox element.
      Thus, Nanog transcription may be regulated through an interaction between Oct4
      and Sox2 or a novel pluripotential cell-specific Sox element-binding factor which
      is prominent in ES cells.

PMID- 15743840
TI  - Overlapping roles of pocket proteins in the myocardium are unmasked by germ line
      deletion of p130 plus heart-specific deletion of Rb.
AB  - The pocket protein family of tumor suppressors, and Rb specifically, have been
      implicated as controlling terminal differentiation in many tissues, including the
      heart. To establish the biological functions of Rb in the heart and overcome the
      early lethality caused by germ line deletion of Rb, we used a Cre/loxP system to
      create conditional, heart-specific Rb-deficient mice. Mice that are deficient in
      Rb exclusively in cardiac myocytes (CRbL/L) are born with the expected Mendelian
      distribution, and the adult mice displayed no change in heart size, myocyte cell
      cycle distribution, myocyte apoptosis, or mechanical function. Since both Rb and
      p130 are expressed in the adult myocardium, we created double-knockout mice
      (CRbL/L p130-/-) to determine it these proteins have a shared role in regulating
      cardiac myocyte cell cycle progression. Adult CRbL/L p130-/- mice demonstrated a
      threefold increase in the heart weight-to-body weight ratio and showed increased
      numbers of bromodeoxyuridine- and phosphorylated histone H3-positive nuclei,
      consistent with persistent myocyte cycling. Likewise, the combined deletion of Rb
      plus p130 up-regulated myocardial expression of Myc, E2F-1, and G1 cyclin
      dependent kinase activities, synergistically. Thus, Rb and p130 have overlapping
      functional roles in vivo to suppress cell cycle activators, including Myc, and
      maintain quiescence in postnatal cardiac muscle.

PMID- 15743843
TI  - Surgical management of knee dislocations. Surgical technique.
AB  - BACKGROUND: The evaluation and management of knee dislocations remain variable
      and controversial. The purpose of this study was to describe our method of
      surgical treatment of knee dislocations with use of a standardized protocol and
      to report the clinical results. METHODS: Forty-seven consecutive patients
      presented with an occult (reduced) or grossly dislocated knee. Fourteen of these
      patients were not included in this series because of confounding variables: four
      had an open knee dislocation, five had vascular injury requiring repair, three
      were treated with external fixation, and two had associated injury. The remaining
      thirty-three patients underwent surgical treatment for the knee dislocation with
      our standard approach. Anatomical repair and/or replacement was performed with
      fresh-frozen allograft tissue. Thirty-one of the thirty-three patients returned
      for subjective and objective evaluation with use of four different knee-rating
      scales at a minimum of twenty-four months after the operation. RESULTS: Nineteen
      of the thirty-one patients were treated acutely (less than three weeks after the
      injury) and twelve, chronically. The mean Lysholm score was 91 points for the
      acutely reconstructed knees and 80 points for the chronically reconstructed
      knees. The Knee Outcome Survey Activities of Daily Living scores averaged 91
      points for the acutely reconstructed knees and 84 points for the chronically
      reconstructed knees. The Knee Outcome Survey Sports Activity scores averaged 89
      points for the acutely reconstructed knees and 69 points for the chronically
      reconstructed knees. According to the Meyers ratings, twenty-three patients had
      an excellent or good score and eight had a fair or poor score. Sixteen of the
      nineteen acutely reconstructed knees and seven of the twelve chronically
      reconstructed knees were given an excellent or good Meyers score. The average
      loss of extension was 1 degrees , and the average loss of flexion was 12 degrees
      . There was no difference in the range of motion between the acutely and
      chronically treated patients. Four acutely reconstructed knees required
      manipulation because of loss of flexion. Laxity tests demonstrated consistently
      improved stability in all patients, with more predictable results in the acutely
      treated patients. CONCLUSIONS: Surgical treatment of the knee dislocations in our
      series provided satisfactory subjective and objective outcomes at two to six
      years postoperatively. The patients who were treated acutely had higher
      subjective scores and better objective restoration of knee stability than did
      patients treated three weeks or more after the injury. Nearly all patients were
      able to perform daily activities with few problems. However, the ability of
      patients to return to high-demand sports and strenuous manual labor was less
      predictable.

PMID- 15743841
TI  - Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in
      mice lacking PTEN in adipose tissue.
AB  - In adipose tissue, insulin controls glucose and lipid metabolism through the
      intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase
      AKT. Phosphatase and a tensin homolog deleted from chromosome 10 (PTEN), a
      negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, is
      hypothesized to inhibit the metabolic effects of insulin. Here we report the
      generation of mice lacking PTEN in adipose tissue. Loss of Pten results in
      improved systemic glucose tolerance and insulin sensitivity, associated with
      decreased fasting insulin levels, increased recruitment of the glucose
      transporter isoform 4 to the cell surface in adipose tissue, and decreased serum
      resistin levels. Mutant animals also exhibit increased insulin signaling and AMP
      kinase activity in the liver. Pten mutant mice are resistant to developing
      streptozotocin-induced diabetes. Adipose-specific Pten deletion, however, does
      not alter adiposity or plasma fatty acids. Our results demonstrate that in vivo
      PTEN is a potent negative regulator of insulin signaling and insulin sensitivity
      in adipose tissue. Furthermore, PTEN may be a promising target for nutritional
      and/or pharmacological interventions aimed at reversing insulin resistance.

PMID- 15743842
TI  - Human Fas-associated factor 1, interacting with ubiquitinated proteins and
      valosin-containing protein, is involved in the ubiquitin-proteasome pathway.
AB  - Human Fas-associated factor 1 (hFAF1) is a novel protein having multiubiquitin
      related domains. We investigated the cellular functions of hFAF1 and found that
      valosin-containing protein (VCP), the multiubiquitin chain-targeting factor in
      the degradation of the ubiquitin-proteasome pathway, is a binding partner of
      hFAF1. hFAF1 is associated with the ubiquitinated proteins via the newly
      identified N-terminal UBA domain and with VCP via the C-terminal UBX domain. The
      overexpression of hFAF1 and a truncated UBA domain inhibited the degradation of
      ubiquitinated proteins and increased cell death. These results suggest that hFAF1
      binding to ubiquitinated protein and VCP is involved in the ubiquitin-proteasome
      pathway. We hypothesize that hFAF1 may serve as a scaffolding protein that
      regulates protein degradation in the ubiquitin-proteasome pathway.

PMID- 15743844
TI  - Standard surgical protocol to treat elbow dislocations with radial head and
      coronoid fractures. Surgical technique.
AB  - BACKGROUND: The results of elbow dislocations with associated radial head and
      coronoid fractures are often poor because of recurrent instability and stiffness
      from prolonged immobilization. We managed these injuries with a standard surgical
      protocol, postulating that early intervention, stable fixation, and repair would
      provide sufficient stability to allow motion at seven to ten days postoperatively
      and enhance functional outcome. METHODS: We retrospectively reviewed the results
      of this treatment performed, at two university-affiliated teaching hospitals, in
      thirty-six consecutive patients (thirty-six elbows) with an elbow dislocation and
      an associated fracture of both the radial head and the coronoid process. Our
      surgical protocol included fixation or replacement of the radial head, fixation
      of the coronoid fracture if possible, repair of associated capsular and lateral
      ligamentous injuries, and in selected cases repair of the medial collateral
      ligament and/or adjuvant-hinged external fixation. Patients were evaluated both
      radiographically and with a clinical examination at the time of the latest follow
      up. RESULTS: At a mean of thirty-four months postoperatively, the flexion
      extension arc of the elbow averaged 112 degrees +/- 11 degrees and forearm
      rotation averaged 136 degrees +/- 16 degrees . The mean Mayo Elbow Performance
      Score was 88 points (range, 45 to 100 points), which corresponded to fifteen
      excellent results, thirteen good results, seven fair results, and one poor
      result. Concentric stability was restored to thirty-four elbows. Eight patients
      had complications requiring a reoperation: two had a synostosis; one, recurrent
      instability; four, hardware removal and elbow release; and one, a wound
      infection. CONCLUSIONS: Use of our surgical protocol for elbow dislocations with
      associated radial head and coronoid fractures restored sufficient elbow stability
      to allow early motion postoperatively, enhancing the functional outcome. We
      recommend early operative repair with a standard protocol for these injuries.

PMID- 15743845
TI  - Use of an intramedullary rod for the treatment of congenital pseudarthrosis of
      the tibia. Surgical technique.
AB  - BACKGROUND: The treatment of congenital pseudarthrosis of the tibia remains
      difficult and controversial. The purpose of this study was to evaluate the long
      term results of a technique consisting of excision of the pseudarthrosis,
      autologous bone-grafting, and insertion of a Williams intramedullary rod into the
      tibia. METHODS: Twenty-one consecutive patients with congenital pseudarthrosis of
      the tibia were managed with this technique between 1978 and 1999, and the results
      were retrospectively reviewed. The mean age of the patients at the time of the
      latest follow-up was 17.2 years (range, seven to twenty-five years), and the mean
      duration of postoperative follow-up was 14.2 years (range, three to twenty
      years). RESULTS: Initial consolidation occurred in eighteen of the twenty-one
      patients. Refracture occurred in twelve patients; five fractures healed with
      closed treatment, five healed after an additional surgical procedure, and two
      ultimately required amputation. Ten patients had an ankle valgus deformity after
      tibial union. Eleven patients had a residual limb-length discrepancy of >2 cm;
      six required a contralateral distal femoral and/or proximal tibial
      epiphyseodesis, two had a tibial lengthening, and one used a shoe-lift. Five
      patients had an amputation: two, because of a recalcitrant fracture; two, because
      of a limb-length discrepancy (6 and 9 cm); and one, because of a chronic lower
      extremity deformity. CONCLUSIONS: This technique produced a satisfactory long
      term functional outcome in sixteen of twenty-one patients and should be
      considered for the management of congenital pseudarthrosis of the tibia.

PMID- 15743846
TI  - Distal humeral fractures treated with noncustom total elbow replacement. Surgical
      technique.
AB  - BACKGROUND: The purpose of this study was to review the cases of patients with a
      distal humeral fracture that was treated with a noncustom total elbow
      arthroplasty. We hypothesized that, on the basis of the functional and clinical
      outcome, total elbow replacement is a reliable option for the treatment of
      elderly patients with a severe, comminuted fracture of the distal part of the
      humerus. METHODS: We retrospectively reviewed forty-nine acute distal humeral
      fractures in forty-eight patients who were treated with total elbow arthroplasty
      as the primary option. The average age of the patients was sixty-seven years.
      Forty-three fractures were followed for at least two years. According to the AO
      classification, five fractures were type A, five were type B, and thirty-three
      were type C. The average age of the forty-three patients was sixty-nine years and
      the average duration of follow-up was seven years. Fourteen patients died during
      the review period. Postoperative clinical function was assessed with use of the
      Mayo elbow performance score, and anteroposterior and lateral radiographs made at
      follow-up examinations were reviewed. RESULTS: At the latest follow-up
      examination, the average flexion arc was 24 degrees (range, 0 degrees to 75
      degrees ) to 131 degrees (range, 100 degrees to 150 degrees ) and the Mayo elbow
      performance score averaged 93 of a possible 100 points. Heterotopic ossification
      was present to some extent in seven elbows, with radiographic abutment noted in
      two. Thirty-two (65%) of the forty-nine elbows had neither a complication nor any
      further surgery from the time of the index arthroplasty to the most recent follow
      up evaluation. Fourteen elbows (29%) had a single complication, and most of them
      did not require further surgery. Ten additional procedures, including five
      revision arthroplasties, were required in nine elbows; five were related to soft
      tissue and five were related to the implant or bone. CONCLUSIONS: Complex distal
      humeral fractures should be assessed primarily for the reliability with which
      they can be reconstructed with osteosynthesis. When osteosynthesis is not
      considered to be feasible, especially in patients who are physiologically older
      and place lower demands on the joint, total elbow arthroplasty can be considered.
      This retrospective review supports a recommendation for total elbow arthroplasty
      for the treatment of an acute distal humeral fracture when strict inclusion
      criteria are observed.

PMID- 15743847
TI  - Anterior cruciate ligament reconstruction with a four-strand hamstring tendon
      autograft. Surgical technique.
AB  - BACKGROUND: In this study, we analyzed the clinical outcomes at a minimum of two
      years following reconstruction of the anterior cruciate ligament with use of a
      four-strand hamstring tendon autograft in patients who had presented with a
      symptomatic torn anterior cruciate ligament. METHODS: One hundred and twenty-two
      consecutive patients who had an isolated, symptomatic anterior tibial subluxation
      associated with rupture of the anterior cruciate ligament were treated with
      reconstruction of the anterior cruciate ligament with a four-strand autologous
      semitendinosus-gracilis tendon graft. One surgeon performed all of the
      operations. Prior to surgery and at the follow-up examination, physical findings
      and functional scores were recorded and knee radiographs were analyzed. Following
      surgery, a six-month rehabilitation regimen was implemented. RESULTS: Eighty-five
      patients (70%) were available for follow-up, which included physical examination,
      scoring of function, KT-1000 arthrometric testing, and radiographs, at a mean of
      twenty-eight months. Seventy-six (89%) of the patients had negative Lachman and
      pivot shift tests. The mean Lysholm score improved from 55 points preoperatively
      to 91 points at the time of follow-up (p < 0.01). The mean Tegner score improved
      from 5 to 6 points (p < 0.01). Sixty-five patients had <3 mm of knee translation
      on arthrometric testing, but six patients with marked laxity were not tested.
      Three patients (4%) had a positive pivot shift test but had no history of
      additional trauma to the knee. Six patients (7%) had a traumatic rupture of the
      graft, occurring at a mean of 10.7 months postoperatively. Assessment of the
      follow-up radiographs demonstrated no evidence of progressive degenerative change
      compared with the appearance on the preoperative radiographs. However, tunnel
      expansion was noted in all patients. The tibial tunnel expanded a mean of 17%
      (range, 0% to 32%), and the femoral tunnel expanded a mean of 29% (range, 0% to
      40%). CONCLUSIONS: Reconstruction of the anterior cruciate ligament with use of a
      four-strand hamstring tendon autograft eliminated anterior tibial subluxation in
      89% of patients who were examined at a minimum of two years postoperatively. The
      overall rate of failure was 11%. The functional knee scores were significantly
      increased at the time of follow-up, but these results did not correlate with the
      results of knee arthrometric testing.

PMID- 15743848
TI  - Primary Souter-Strathclyde total elbow prosthesis in rheumatoid arthritis.
      Surgical technique.
AB  - BACKGROUND: Total elbow arthroplasty is a well-established treatment for the
      painful elbow joint in patients with rheumatoid arthritis. We present the results
      of what we believe to be the first prospective study of the Souter-Strathclyde
      total elbow prosthesis. METHODS: Between June 1982 and December 2000, 204 primary
      total elbow prostheses were inserted in 166 patients who had rheumatoid
      arthritis. No patient was lost to follow-up. The mean duration of follow-up was
      6.4 years. All patients were examined preoperatively, at one and two years
      postoperatively, and at regular intervals thereafter. RESULTS: Six of the 204
      elbows had pain at rest at the time of the latest follow-up. Ten patients (ten
      elbows) without previous neurological symptoms had development of paresthesias in
      the distribution of the ulnar nerve postoperatively. Patients who had pain at
      rest or at night and those who had ulnar nerve symptoms preoperatively were found
      to have a significant chance of having the same complaints postoperatively. Pain
      at rest or at night and a decrease in function during the follow-up period were
      associated with humeral loosening. Twenty-four elbows had revision of the total
      elbow prosthesis because of loosening of the humeral component (ten), loosening
      after fracture (six), dislocation (four), infection (two), restricted range of
      motion (one), or fracture of the middle part of the humeral shaft, proximal to
      the prosthesis (one). One prosthesis was removed because of humeral loosening,
      and eight were removed because of deep infection. Another five prostheses were
      radiographically loose at the time of the latest follow-up. The rate of implant
      survival, according to the method of Kaplan-Meier, was 77.4% after ten years and
      65.2% after eighteen years. CONCLUSIONS: Total elbow replacement is associated
      with a high complication rate and therefore may be warranted only for seriously
      disabled patients. Currently, the results associated with the Souter-Strathclyde
      total elbow prosthesis are comparable with the results associated with other
      prostheses, but loosening of the humeral component remains a concern.

PMID- 15743849
TI  - Ligament reconstruction with or without tendon interposition to treat primary
      thumb carpometacarpal osteoarthritis. Surgical technique.
AB  - BACKGROUND: Trapezial excision with ligament reconstruction and trapezial
      excision with ligament reconstruction combined with tendon interposition have
      proven to be highly effective techniques for treating primary osteoarthritis of
      the thumb carpometacarpal joint. To determine whether tendon interposition and
      proximal migration of the thumb metacarpal affect the objective and subjective
      outcomes, we compared the long-term outcomes of these two procedures performed in
      similar patient groups. METHODS: Forty-three patients (fifty-two thumbs) were
      randomized to undergo either trapezial excision with ligament reconstruction or
      the same procedure combined with tendon interposition. Fifteen patients treated
      with ligament reconstruction (group I) and sixteen patients treated with the same
      procedure with concomitant tendon interposition (group II) were evaluated after a
      mean follow-up period of 48.2 months. The outcomes were assessed with the Buck
      Gramcko score, with the total score calculated on the basis of the objective and
      subjective results. The ability to perform activities requiring use of the thumb
      and to return to work was analyzed as well. Radiographs were evaluated to
      determine the amount of proximal metacarpal migration at rest and under stress.
      RESULTS: Postoperatively, the mean total Buck-Gramcko score was rated as
      excellent in group I and as good in group II (p = 0.036). Group I had
      significantly better mean scores for palmar and radial abduction, cosmetic
      appearance, and willingness to undergo the surgery again under similar
      circumstances (p < 0.05). The mean scores for tip-pinch strength and the mean
      subjective scores for pain, strength, daily function, dexterity, and overall
      satisfaction did not differ significantly between the groups. Both groups had
      satisfactory results with regard to their performance of activities of daily
      living and their ability to return to work. With the numbers available, the
      amount of proximal metacarpal migration, at rest and under stress, did not differ
      significantly between the groups. CONCLUSIONS: Tendon interposition does not
      affect the outcome after the ligament reconstruction for the treatment of
      osteoarthritis of the thumb carpometacarpal joint. Furthermore, proximal
      migration of the thumb metacarpal does not appear to influence the functional
      outcome.

PMID- 15743850
TI  - Salvage of the failed Keller resection arthroplasty. Surgical technique.
AB  - BACKGROUND: A number of typical complications have been associated with Keller
      resection arthroplasty. Recurrent valgus deformity, cock-up deformity, and a
      flail toe may be difficult problems for the treating surgeon because options for
      salvage are limited. In this study, we evaluated arthrodesis of the first
      metatarsophalangeal joint as a salvage technique following a failed Keller
      procedure. In addition, the outcomes of motion-preserving procedures were
      reviewed in a separate series. METHODS: Arthrodesis of the first
      metatarsophalangeal joint was performed in twenty-eight patients (twenty-nine
      feet, group A), and either a repeat Keller procedure or an isolated soft-tissue
      release was performed in eighteen patients (twenty-one feet, group B). The
      patients were evaluated at least twenty-four months postoperatively, with a
      personal interview and a clinical examination with use of a modification of the
      hallux metatarsal-interphalangeal scale. Radiographs were also made for the group
      treated with the arthrodesis. RESULTS: In group A, the average duration of follow
      up was thirty-six months and fusion was achieved in twenty-six of the twenty-nine
      feet. Satisfaction was excellent or good in twenty-three cases, and the
      postoperative score according to the modified hallux metatarsal-interphalangeal
      scale averaged 76 points (maximum, 90 points). A repeat arthrodesis was necessary
      in five feet because of malposition or pseudarthrosis. In group B, the average
      duration of follow-up was seventy-four months. Satisfaction was excellent or good
      in only six cases, and the patient was dissatisfied in eleven cases. The score
      according to the modified hallux metatarsal-interphalangeal scale averaged 48
      points. Valgus deviation and cock-up deformity had recurred in the majority of
      the feet at the time of follow-up. CONCLUSIONS: Although it is more technically
      demanding, we recommend arthrodesis for salvage following a failed Keller
      procedure since it may be associated with a higher rate of patient satisfaction
      and better clinical results.

PMID- 15743851
TI  - Debridement arthroplasty for primary osteoarthritis of the elbow. Surgical
      technique.
AB  - BACKGROUND: Formal and more aggressive debridement procedures have been described
      for the treatment of advanced primary osteoarthritis of the elbow. However, the
      literature contains little information on the results of long-term follow-up. The
      purpose of this study was to evaluate outcomes at an average of ten years after
      debridement arthroplasties performed through a posteromedial approach. METHODS:
      Thirty-three elbows with primary osteoarthritis in thirty-two patients treated
      with debridement arthroplasty were available for clinical follow-up evaluation.
      Through a posteromedial approach, the flexor-pronator muscle origin was reflected
      from the medial epicondyle and the joint was opened, preserving the anterior
      oblique bundle of the medial collateral ligament. The ulnar nerve was
      decompressed in all patients. Osteophytes were removed from the anterior, medial,
      and posterior sides of the elbow joint. In nine elbows, osteophytes from the
      lateral compartment were removed through an additional lateral approach. The mean
      age at the time of the operation was fifty years. The mean duration of follow-up
      was 121 months, and nineteen elbows were followed for more than ten years.
      RESULTS: The mean preoperative limitation of extension of 31 degrees was reduced
      to 24 degrees , and the mean preoperative flexion of 101 degrees improved to 118
      degrees (p < 0.001). The mean arc of movement improved by 24 degrees . The mean
      Japanese Orthopaedic Association elbow score was 83 points at the latest follow
      up evaluation compared with 60 points preoperatively (p < 0.001). Of twenty-five
      patients who had performed heavy manual work, nineteen (76%) returned to their
      previous job or an equivalent job. At the latest examination of the nineteen
      elbows followed for more than ten years, the limitation of extension was found to
      have increased by 7 degrees compared with the limitation noted at one year (p <
      0.009); the mean arc of flexion had remained the same. Three elbows required a
      reoperation. Overall, 85% of the elbows were satisfactory to the patients.
      CONCLUSIONS: Debridement arthroplasty through a posteromedial approach can
      provide stable and reliable long-term results with regard to relief of pain,
      gains in range of motion, and the patient's ability to return to his or her
      previous occupation. In our series, a modest loss of extension was observed at
      ten years, whereas the arc of flexion remained consistent.

PMID- 15743852
TI  - Treatment of osteonecrosis of the femoral head with implantation of autologous
      bone-marrow cells. Surgical technique.
AB  - BACKGROUND: Aseptic nontraumatic osteonecrosis of the femoral head is a disorder
      that can lead to femoral head collapse and the need for total hip replacement.
      Since osteonecrosis may be a disease of mesenchymal cells or bone cells, the
      possibility has been raised that bone marrow containing osteogenic precursors
      implanted into a necrotic lesion of the femoral head may be of benefit in the
      treatment of this condition. For this reason, we studied the implantation of
      autologous bone-marrow mononuclear cells in a necrotic lesion of the femoral head
      to determine the effect on the clinical symptoms and the stage and volume of
      osteonecrosis. METHODS: We studied thirteen patients (eighteen hips) with stage-I
      or II osteonecrosis of the femoral head, according to the system of the
      Association Research Circulation Osseous. The hips were allocated to a program of
      either core decompression (the control group) or core decompression and
      implantation of autologous bone-marrow mononuclear cells (the bone-marrow-graft
      group). Both patients and assessors were blind with respect to treatment-group
      assignment. The primary outcomes studied were safety, clinical symptoms, and
      disease progression. RESULTS: After twenty-four months, there was a significant
      reduction in pain (p = 0.021) and in joint symptoms measured with the Lequesne
      index (p = 0.001) and the WOMAC index (p = 0.013) within the bone-marrow-graft
      group. At twenty-four months, five of the eight hips in the control group had
      deteriorated to stage III, whereas only one of the ten hips in the bone-marrow
      graft group had progressed to this stage. Survival analysis showed a significant
      difference in the time to collapse between the two groups (p = 0.016).
      Implantation of bone-marrow mononuclear cells was associated with only minor side
      effects. CONCLUSIONS: Implantation of autologous bone-marrow mononuclear cells
      appears to be a safe and effective treatment for early stages of osteonecrosis of
      the femoral head. Although the findings of this study are promising, their
      interpretation is limited because of the small number of patients and the short
      duration of follow-up. Further study is needed to confirm the results.

PMID- 15743853
TI  - Inferior patellar pole avulsion fractures: osteosynthesis compared with pole
      resection. Surgical technique.
AB  - BACKGROUND: The ideal treatment for avulsion fractures of the inferior pole of
      the patella has not yet been identified. The options include (1) internal
      fixation of the pole fragment and (2) resection of the avulsed fragment and
      repair of the patellar ligament to the patella. We are not aware of any previous
      study in which the results of internal fixation have been compared with those of
      pole resection. The purpose of the present study was to compare the long-term
      results of internal fixation (with use of a basket plate) with those of pole
      resection. METHODS: We retrospectively studied two groups of patients who had had
      operative treatment of an avulsion fracture of the inferior patellar pole between
      1990 and 1997. Fourteen patients had had internal fixation with a basket plate,
      and fourteen had had pole resection with patellar ligament repair. Eleven
      patients who had had internal fixation (Group A) and thirteen patients who had
      had pole resection (Group B) were followed for an average of 4.6 years. The final
      evaluation was based on the patellofemoral score, and the patellar height was
      measured radiographically. RESULTS: The average patellofemoral score (maximum,
      100 points) was 94.1 points in Group A and 81.2 points in Group B. Significant
      differences between the groups were noted with regard to knee pain, level of
      activity, and range of motion. Normal patellar height was found in ten of eleven
      patients in Group A and in three of thirteen patients in Group B. Patella baja
      was significantly associated with a poor functional outcome. CONCLUSIONS: In
      patients who have sustained an avulsion fracture of the inferior patellar pole,
      the normal height of the patella can be maintained by preserving the patellar
      pole. In contrast with pole resection, which requires postoperative
      immobilization, internal fixation with a basket plate allows for immediate
      mobilization and early weight-bearing. The present study indicates that internal
      fixation with use of a basket plate can provide better clinical results.

PMID- 15743854
TI  - Selective neurotization of the median nerve in the arm to treat brachial plexus
      palsy. Surgical technique.
AB  - BACKGROUND: The current method for treatment of median nerve palsy after a
      brachial plexus injury is unpredictable. On the basis of an anatomic study of the
      median nerve in the arm, we present a new method of selective neurotization of
      the median nerve. METHODS: Internal topographic features of the fascicular groups
      of the median nerve were observed in seventeen cadavera. On the basis of the
      anatomical results, selective neurotization of the posterior fascicular group of
      the median nerve in the arm was performed in one patient with a complete brachial
      plexus palsy. RESULTS: In the distal half of the arm, the branches of the median
      nerve consistently collect into three fascicular groups, which are located at the
      anterior, middle, and posterior parts of the median nerve trunk. The anterior
      fascicular group is composed of the branches to the pronator teres and the flexor
      carpi radialis, the posterior fascicular group is composed mainly of the anterior
      interosseous nerve and the branches to the palmaris longus, and the middle
      fascicular group is made up mostly of the branches to the hand and the flexor
      digitorum superficialis. A transfer of the full length of the phrenic nerve was
      used to selectively reinnervate the posterior fascicular group of the median
      nerve in a patient with a complete brachial plexus palsy. The muscles supplied by
      the posterior fascicular group regained Grade-4 power, according to the system of
      the Medical Research Council, sixteen months after surgery. CONCLUSIONS: The
      typical arrangement of the fascicular groups of the median nerve in the arm
      favors the technique of selective neurotization, which has been used effectively
      in one patient to date.

PMID- 15743855
TI  - Management of Mason type-III radial head fractures with a titanium prosthesis,
      ligament repair, and early mobilization. Surgical technique.
AB  - BACKGROUND: Radial head fractures often occur in association with other elbow
      fractures and soft-tissue injuries. Radial head replacement is indicated for
      irreparable radial head fractures associated with elbow instability. The purpose
      of this study was to analyze the results after treatment of such injuries with a
      titanium radial head prosthesis, repair of torn collateral ligaments, and early
      mobilization of the elbow. MATERIALS: Sixteen patients with sixteen Mason type
      III radial head fractures and collateral ligament injury were treated with use of
      a titanium radial head prosthesis over a five-year period at the Royal Adelaide
      Hospital and Modbury Public Hospital in South Australia. The surgery was
      performed acutely in ten patients and was delayed an average of thirty-seven days
      (range, fifteen to seventy-nine days) in six. All patients were followed
      clinically and radiographically for a mean of 2.8 years (range, 1.2 to 4.3
      years). RESULTS: Eight patients had an excellent result; five, a good result; and
      three, a fair result, according to the Mayo Elbow Performance Score. The three
      fair results occurred in patients with delayed surgery. The mean flexion
      contracture was 15 degrees (range, 0 degrees to 42 degrees ), with an average
      loss of 10 degrees (range, 0 degrees to 25 degrees ) of full flexion compared
      with that of the contralateral elbow. Both pronation and supination decreased an
      average of 12 degrees (range, 0 degrees to 45 degrees ) compared with that of the
      contralateral forearm. CONCLUSIONS: The results of treatment of Mason type-III
      radial head fractures with a monoblock titanium radial head prosthesis and soft
      tissue reconstruction are satisfactory. Early mobilization of the elbow is
      important for the restoration of elbow range of motion and function.

PMID- 15743856
TI  - Risk factors for pre-eclampsia at antenatal booking: systematic review of
      controlled studies.
AB  - OBJECTIVE: To determine the risk of pre-eclampsia associated with factors that
      may be present at antenatal booking. DESIGN: Systematic review of controlled
      studies published 1966-2002. DATA SYNTHESIS: Unadjusted relative risks were
      calculated from published data. RESULTS: Controlled cohort studies showed that
      the risk of pre-eclampsia is increased in women with a previous history of pre
      eclampsia (relative risk 7.19, 95% confidence interval 5.85 to 8.83) and in those
      with antiphospholipids antibodies (9.72, 4.34 to 21.75), pre-existing diabetes
      (3.56, 2.54 to 4.99), multiple (twin) pregnancy (2.93, 2.04 to 4.21), nulliparity
      (2.91, 1.28 to 6.61), family history (2.90, 1.70 to 4.93), raised blood pressure
      (diastolic > or = 80 mm Hg) at booking (1.38, 1.01 to 1.87), raised body mass
      index before pregnancy (2.47, 1.66 to 3.67) or at booking (1.55, 1.28 to 1.88),
      or maternal age > or = 40 (1.96, 1.34 to 2.87, for multiparous women). Individual
      studies show that risk is also increased with an interval of 10 years or more
      since a previous pregnancy, autoimmune disease, renal disease, and chronic
      hypertension. CONCLUSIONS: These factors and the underlying evidence base can be
      used to assess risk at booking so that a suitable surveillance routine to detect
      pre-eclampsia can be planned for the rest of the pregnancy.

PMID- 15743857
TI  - Soluble cytokine receptor treatment in experimental orthodontic tooth movement in
      the rat.
AB  - Pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis
      factor-alpha (TNF-alpha), are believed to play a role in the biological processes
      involved in the course of orthodontic tooth movement and especially in root
      resorption. The inhibition of cytokine activity, e.g. by soluble receptors, could
      be beneficial in reducing this unwanted side-effect. The aim of this study was to
      investigate the role of cytokines IL-1 and TNF-alpha in the course of
      experimentally induced tooth movement. The upper left first molar was moved
      orthodontically in 80 male Wistar rats using a coil spring with a force of 0.5 N.
      Starting at day -1, three groups of 20 animals each received daily
      intraperitoneal injections (ip) of 2 ml of 1 mug/ml soluble receptors (a) to IL
      1(sIL-RII), (b) to TNF-alpha (sTNF-alpha-RI) and (c) a combination of (a) and
      (b). Twenty animals served as the control. After 3, 6, 9 and 12 days, the animals
      were killed in groups of five. The amount of tooth movement was registered and
      the maxillae were prepared for histological and histomorphometric analysis.
      Osteoclasts and odontoclasts were identified using tartrate-resistant acid
      phosphatase (TRAP) histochemistry. The amount of tooth movement was reduced in
      all receptor-treated groups by approximately 50 per cent. At the same time, the
      number of TRAP-positive cells on the desmodontal bone surface and on the surface
      of the roots was reduced. Thus, systemic application of soluble receptors to IL-1
      and TNF-alpha following experimental induction of tooth movement in the rat
      reduced the number of osteoclasts as well as odontoclasts.

PMID- 15743858
TI  - Three-dimensional numerical simulation of dental implants as orthodontic
      anchorage.
AB  - Endosseous oral implants have been used as orthodontic anchorage in subjects with
      multiple tooth agenesis, and their application under orthodontic loading has been
      demonstrated clinically and experimentally. The aim of this investigation was to
      examine three-dimensional (3D) bone and implant finite element (FE) models. The
      first model assumed that there was no osseointegration and the second that full
      osseointegration had occurred. These models were used to determine the pattern
      and distribution of stresses within the ITI-Bonefit endosseous implant and its
      supporting tissues when used as an orthodontic anchorage unit. The study examined
      a threaded implant placed in an edentulous segment of a human mandible with
      cortical and cancellous bone. The results, using both models, indicated that the
      maximum stresses were always located around the neck of the implant, in the
      marginal bone. Thus, this area should be preserved clinically in order to
      maintain the bone-implant interface structurally and functionally.

PMID- 15743859
TI  - Growth regulation of the rat mandibular condyle and femoral head by transforming
      growth factor-{beta}1, fibroblast growth factor-2 and insulin-like growth factor
      I.
AB  - The mandibular condyle is a major growth site and is known to adapt to functional
      factors. Numerous studies have been performed on the effects of growth factors on
      the metabolism of primary cartilages, but only a few investigations have examined
      their action on primary and secondary cartilages. Therefore, the purpose of this
      study was to compare the effects of insulin-like growth factor-I (IGF-I),
      transforming growth factor-beta(1) (TGF-beta(1)), and fibroblast growth factor-2
      (FGF-2) on the growth of secondary cartilage from the mandibular condyle and
      primary cartilage from the femoral head of new-born rats. In addition, synergy
      between these growth factors was investigated. The level of glycosaminoglycan
      (GAG) and DNA synthesis was analysed after 5 days in culture with the growth
      factors. The effects of TGF-beta(1) and FGF-2 on growth, tissue organization, and
      the GAG and collagen content were also evaluated. The stimulation of cell
      proliferation by the growth factors was higher in the mandibular condyles than in
      the femoral heads. The content of the matrix components was reduced more by FGF-2
      in the mandibular condyles than in the femoral heads. Both TGF-beta(1) and FGF-2
      antagonized the stimulatory effects of IGF-I on GAG synthesis in the two types of
      cartilage. In contrast, the total growth of mandibular condyles was not affected
      by TGF-beta(1) and FGF-2 while that of femoral heads was strongly reduced. This
      was mainly due to the inhibition of chondrocyte hypertrophy. These results show
      that in spite of the extensive effects of growth factors on the metabolism of
      mandibular condyles, their dimensional growth was not affected.

PMID- 15743860
TI  - The effect of oral ipriflavone on the rat mandible during growth.
AB  - Different types of ipriflavone (IF) have been reported to be effective when used
      as a remedy for bone loss due to osteoporosis. However, no information is
      available regarding the relationship between IF and jaw bone structure. The aim
      of this study was to examine the effect of IF on rat mandibles during the growth
      stage. Thirty-two 5-week-old Wistar male rats were divided into four groups. The
      control group was fed a standard diet, group A received a low calcium diet
      (calcium content 30 per cent of the standard diet) for 6 weeks, and the other two
      groups were fed a low calcium diet for 3 weeks and then a standard diet without
      IF (group B) or with IF (group C) for 3 weeks. In addition, distilled water was
      provided for all groups. The effects of IF on mandibular size and bone mineral
      content were investigated, using lateral cephalometric analysis and peripheral
      quantitative computed tomography (pQCT). For mandibular length, the control group
      showed a significantly higher value than groups A and B (P < 0.01, P < 0.05,
      respectively), while group C demonstrated a significantly higher value than group
      A (P < 0.01). In addition, the control group and group C showed significantly
      higher values for mandibular ramus height than group A (P < 0.01). However, bone
      mineral density in trabecular bone was significantly higher in the control group
      than in the other groups (P < 0.01) and bone mineral density in cortical bone was
      significantly higher in the control group than groups A, B and C (P < 0.01, P <
      0.01, P < 0.05, respectively). Bone mineral density in both trabecular and
      cortical bone was significantly higher in group C than in groups A and B (P <
      0.01, P < 0.05, respectively). These results indicate that complete recovery from
      calcium deficiency to the level of the control group may not be attainable, even
      though IF enhances calcium absorption to act on bone cells and promote bone
      construction. The importance of calcium intake in the early stages of development
      was confirmed. These findings also suggest an effect of IF on jaw bone structure.

PMID- 15743861
TI  - Neurocranial morphology and growth in Williams syndrome.
AB  - Williams syndrome (WS) is a rare congenital neurodevelopmental disorder with
      distinctive facial features, cardiovascular abnormalities, short stature, mental
      retardation, and behaviour and cognitive characteristics. The aim of this study
      was to describe the neurocranial morphology and growth in a group of 62
      individuals with WS. The neurocranium was analysed on lateral cephalograms and
      comparisons were made with neurocranial standards from longitudinal data derived
      from the Oslo University Craniofacial Growth Archive. The size and morphology of
      the neurocranium in WS subjects differed from controls. Females as a group showed
      greater differences than males. The posterior cranial base length was shorter in
      both WS males and females, and the anterior cranial base length was shorter in WS
      females whereas it was close to normal in the WS male group. The cranial base
      angle was, however, not different from the control groups. A flattening was seen
      in the superior aspect of the parietal bone in both WS males and females. In the
      posterior part of the neurocranium, the prominence of the occipital bone was
      larger than in the control groups, which was also reflected in a larger total
      length of the neurocranium. The thickness of the frontal and occipital bones was
      considerably greater than in the control group. The deviant size and morphology
      of the neurocranium in WS subjects was already established in the youngest age
      group and maintained throughout the observation period. The growth pattern of the
      neurocranium in WS subjects seemed to be similar to that of the control groups,
      except in a few individuals.

PMID- 15743862
TI  - The relationship of distinct craniofacial features between Turner syndrome
      females and their parents.
AB  - The present study aimed to assess the relationship of craniofacial features
      between females with Turner syndrome (TS) and their parents. Lateral cephalograms
      of 63 TS females and 80 family members with normal karyotype were analysed using
      13 linear and eight angular cephalometric measurements. The statistical
      differences of the measurements between adult TS females and their mothers (n =
      41) and between adult TS females and their adult sisters (n = 27) were calculated
      to define the distinct craniofacial features of subjects with TS. Regression
      models were computed to assess the association of distinct craniofacial features
      between TS females and their parents (n = 41 for mothers and n = 12 for fathers).
      Distinct craniofacial features of the subjects with TS were an increased cranial
      base flexion, shortened posterior cranial base length (S-Ba), retrognathic
      maxilla and mandible (<SNB), shortened distance of the palate, glenoid fossa (S
      Art) and gonion (S-Go) from sella, shortened body and total length (Art-Pog) of
      the mandible and increased vertical angles of the facial skeleton. The mothers' S
      Ba (P = 0.001), <SNB (P < 0.001), S-Go (P < 0.01) and S-Art (P < 0.05)
      measurements predicted well the corresponding measurements of their daughters
      with TS. Fathers had a significant association with their TS daughters in Art-Pog
      (P < 0.01) measurement. The results suggest that maternal influences contribute
      to the growth of a distinct cranial base and to the magnitude of mandibular
      retrognathism of subjects with TS.

PMID- 15743863
TI  - A determination of bite force in northern Japanese children.
AB  - The bite force of 2594 school children (1248 males and 1346 females) living in
      northern Japan was investigated during oral health examinations in May and June
      2001, using a new type of occlusal force gauge. The subjects were recruited from
      a variety of educational institutes and comprised: 73 nursery (3-5 years old),
      1019 primary (6-11 years old), 902 junior high (12-14 years old) and 600 high (15
      17 years old) school children. The measuring apparatus consisted of a hydraulic
      pressure gauge, with a bite element encased in a plastic tube. The bite force was
      measured at the first molar or second primary molar in the children presenting in
      the permanent and primary dentitions, respectively. The findings revealed
      significant variations in bite force between children of different ages. The
      average bite force was 186.2 N in males and 203.4 N in females of nursery school
      children; 374.4 N in males and 330.5 N in females of primary school children;
      514.9 N in males and 448.7 N in females of junior high school children; and 545.3
      N in males and 395.2 N in females of high school children. The prevalence of
      malocclusion in the nursery school children was found to be less than 30 per
      cent, which contrasted with almost 70 per cent in the high school children.

PMID- 15743864
TI  - Molar bite force in relation to occlusion, craniofacial dimensions, and head
      posture in pre-orthodontic children.
AB  - The present study examined bite force in relation to occlusion, craniofacial
      dimensions, and head posture. The sample comprised 88 children (48 girls, 40
      boys) aged 7-13 years, sequentially admitted for orthodontic treatment of
      malocclusions entiling health risks. Bite force was measured in the molar region
      by means of a pressure transducer. Angle classification, number of teeth and
      contact in the intercuspal position (ICP) were recorded and dental arch widths
      were measured on plaster casts. Craniofacial dimensions and head posture were
      recorded from lateral cephalometric radiographs taken with the subject standing
      with their head in a standardized posture (mirror position). Associations were
      assessed by Spearman correlations and multiple stepwise regression analyses.The
      maximum bite force increased significantly with age in girls, with teeth in
      occlusal contact in boys, and with increasing number of erupted teeth in both
      genders. Bite force did not vary significantly between the Angle malocclusion
      types. Only in boys was there a clear correlation between bite force and
      craniofacial morphology: cranial base length (n-ba, n-ar), posterior face height
      (s-tgo, ar-tgo), vertical jaw relationship (NL-ML), mandibular inclination (NSL
      ML), form (ML-RL) and length (pg-tgo), and inclination of the lower incisors (Ili
      ML). Multiple regression analysis showed that the vertical jaw relationship (P <
      0.001) and the number of teeth present (P < 0.01) were the most important factors
      for the magnitude of bite force in boys. In girls, the most important factor was
      the number of teeth present (P < 0.001). No correlations between bite force and
      head posture were found.

PMID- 15743865
TI  - Factors influencing the wearing of protective gloves in orthodontic practice.
AB  - The purpose of this study was to explore how wearing, or not wearing, protective
      gloves affects the efficiency of orthodontists in performing certain orthodontic
      procedures. Thirty-six volunteers were randomly selected from members of the
      Taiwan Association of Orthodontists. A visual analogue scale (VAS) was used to
      determine the degree of convenience subjects felt in performing 11 specified
      orthodontic procedures, with and without gloves. In addition, the time required
      to bend round and rectangular archwires and to tie and untie ligature wires was
      recorded.The results showed that for 10 of the 11 orthodontic tasks there was
      perceived to be no difference when wearing, or not wearing, gloves. Only when
      bending a round archwire was there perceived to be a difference. When the four
      orthodontic procedures were undertaken on a typodont and timed, no significant
      difference was found between the use of gloves/no gloves.

PMID- 15743866
TI  - Influence of autoclave sterilization on the surface parameters and mechanical
      properties of six orthodontic wires.
AB  - Orthodontic wires are frequently packaged in individual sealed bags in order to
      avoid cross-contamination. The instructions on the wrapper generally advise
      autoclave sterilization of the package and its contents if additional protection
      is desired. However, sterilization can modify the surface parameters and the
      mechanical properties of many types of material. The aim of this research was to
      determine the influence of one of the most widely used sterilization processes,
      autoclaving (18 minutes at 134 degrees C, as recommended by the French Ministry
      of Health), on the surface parameters and mechanical properties of six wires
      currently used in orthodontics (one stainless steel alloy: Tru-Chrome RMO; two
      nickel-titanium shape memory alloys: Neo Sentalloy and Neo Sentalloy with
      Ionguard GAC; and three titanium-molybdenum alloys: TMA(R) and Low Friction TMA
      Ormco and Resolve GAC). The alloys were analysed on receipt and after
      sterilization, using surface structure observation techniques, including optical,
      scanning electron and atomic force microscopy and profilometry. The mechanical
      properties were assessed by three-point bending tests. The results showed that
      autoclave sterilization had no adverse effects on the surface parameters or on
      the selected mechanical properties. This supports the possibility for
      practitioners to systematically sterilize wires before placing them in the oral
      environment.

PMID- 15743867
TI  - A comparison of the Twin Block and Herbst mandibular advancement splints in the
      treatment of patients with obstructive sleep apnoea: a prospective study.
AB  - This prospective, randomized, crossover study of 16 patients with obstructive
      sleep apnoea (OSA) [12 males, four females; median body mass index (BMI) 29.2
      kg/m(2) (range 23.8-51.1); median age 44.8 years (range 24.0-68.4)] analysed the
      efficacy of the Twin Block (TB) in relation to the Herbst appliance as a
      mandibular advancement splint (MAS). Each subject was fitted with a TB and Herbst
      MAS in a random order with a washout period of 2 weeks between appliances. Once
      each patient was subjectively happy with the performance of each appliance,
      questionnaires and a visual analogue scale (VAS) were used to determine
      differences in snoring, daytime sleepiness, quality of life, side-effects of the
      appliances and patient preference. All patients underwent overnight domiciliary
      sleep recordings prior to and after fitting each appliance in order to
      objectively assess sleep quality in terms of the apnoea-hypopnoea index (AHI),
      snoring frequency and arterial oxygen saturation. The results suggested that
      there was no difference in the treatment performance of the TB and Herbst MAS for
      AHI (P = 0.71), snoring frequency (P = 0.49), arterial blood oxygen saturation (P
      = 0.97), quality of life and side-effects. The Herbst MAS proved to be the more
      effective appliance for reducing daytime sleepiness (P = 0.04) and was the more
      popular appliance among the patients. Side-effects with both appliances were
      minor and improved in the longer term. The TB MAS represents a viable alternative
      to the Herbst MAS in the treatment of patients with OSA.

PMID- 15743868
TI  - Craniofacial morphology, head posture, and nasal respiratory resistance in
      obstructive sleep apnoea: an inter-ethnic comparison.
AB  - The aim of this study was to measure craniofacial morphology and nasal
      respiratory resistance (NRR) in Malay, Indian and Chinese subjects with
      obstructive sleep apnoea (OSA). The sample consisted of 34 male subjects, 27-52
      years of age (Malay n = 11, which included five mild and six moderate-severe OSA;
      Indian n = 11, which included six mild and five moderate-severe OSA; and Chinese
      n = 12, which included six mild and six moderate-severe OSA) diagnosed using
      overnight polysomnography. After use of a decongestant, NRR was recorded using
      anterior and posterior rhinomanometry. Standardized lateral cephalometric
      radiographs were used to record linear and angular dimensions. Malay subjects
      with moderate-severe OSA had a shorter maxillary (sp-pm) and mandibular (gn-go)
      length when compared with a mild OSA reference sample (P < 0.05). The hyoid bone
      was located more caudally in the Chinese moderate-severe subjects (hy-NL, hy
      ML)(P < 0.05), and may be a useful diagnostic indicator for severity in this
      racial group. No pattern of differences for NRR was seen between the moderate
      severe and mild OSA subjects. The consistently lower values for nasopharyngeal
      resistance in all the moderate-severe subjects when compared with the mild group
      may indicate that some compensation at this level of the airway had taken place.
      Strong positive correlations between craniocervical angulation (NL/OPT) and total
      airway resistance and the turbulent component of flow (k(2)) suggest that head
      posture is sensitive to fluctuations in airway resistance (P < 0.01).

PMID- 15743869
TI  - The effect of heritability on Bolton tooth-size discrepancy.
AB  - The purpose of this study was to determine the possible effect of genetic factors
      on Bolton tooth-size discrepancy. Subjects who applied for orthodontic treatment
      and their siblings (106 females and 78 males) were included in the study. The
      ages of the subjects ranged from 13 to 21 years. The siblings were grouped
      according to gender: male-male (24 pairs), female-female (38 pairs) and male
      female (30 pairs). Mesio-distal tooth size was measured using a pair of dividers
      with fine tips, and Bolton anterior and overall ratios were calculated. The
      effect of heritability on Bolton ratios was studied by means of Harvey's mixed
      model least-squared and maximum likelihood computer program (LSMLMW) model type
      II. Statistical analysis showed that heritability was effective on Bolton tooth
      size discrepancy in all groups except the male-female group. Siblings of the same
      gender showed high heritability for anterior and overall ratios, but no
      statistically significant difference was observed in the siblings of different
      gender.

PMID- 15743870
TI  - Right hemisphere language functions and schizophrenia: the forgotten hemisphere?
AB  - This review highlights the importance of right hemisphere language functions for
      successful social communication and advances the hypothesis that the core deficit
      in psychosis is a failure of segregation of right from left hemisphere functions.
      Lesion studies of stroke patients and dichotic listening and functional imaging
      studies of healthy people have shown that some language functions are mediated by
      the right hemisphere rather than the left. These functions include discourse
      planning/comprehension, understanding humour, sarcasm, metaphors and indirect
      requests, and the generation/comprehension of emotional prosody. Behavioural
      evidence indicates that patients with typical schizophrenic illnesses perform
      poorly on tests of these functions, and aspects of these functions are disturbed
      in schizo-affective and affective psychoses. The higher order language functions
      mediated by the right hemisphere are essential to an accurate understanding of
      someone's communicative intent, and the deficits displayed by patients with
      schizophrenia may make a significant contribution to their social interaction
      deficits. We outline a bi-hemispheric theory of the neural basis of language that
      emphasizes the role of the sapiens-specific cerebral torque in determining the
      four-chambered nature of the human brain in relation to the origins of language
      and the symptoms of schizophrenia. Future studies of abnormal lateralization of
      left hemisphere language functions need to take account of the consequences of a
      failure of lateralization of language functions to the right as well as the left
      hemisphere.

PMID- 15743871
TI  - Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex
      partial status epilepticus.
AB  - Diffusion-weighted MRI (DWI) and perfusion MRI (PI) have been mainly applied in
      acute stroke, but may provide information in the peri-ictal phase in epilepsy
      patients. Both transient reductions of brain water diffusion, namely a low
      apparent diffusion coefficient (ADC), and signs of hyperperfusion have been
      reported in experimental and human epilepsy case studies. We studied 10 patients
      with complex partial status epilepticus (CPSE) with serial MRI including DWI and
      PI. All patients showed regional hyperintensity on DWI, and a reduction of the
      ADC in (i) the hippocampal formation and the pulvinar region of the thalamus (six
      out of 10 patients), (ii) the pulvinar and cortical regions (two out of 10),
      (iii) the hippocampal formation only (one out of 10), and (iv) the hippocampal
      formation, the pulvinar and the cortex (one out of 10). In all patients a close
      spatial correlation of focal hyperperfusion with areas of ADC/DWI change was
      present. In two patients hyperperfusion was confirmed in additional SPECT (single
      photon emission computed tomography) studies. All patients received follow-up MRI
      examinations showing partial or complete resolution of diffusion and perfusion
      abnormalities depending on the length of the follow-up interval. The clinical
      course, EEG and SPECT results all indicate that MRI detected changes related to
      prolonged epileptic activity. Combined PI and DWI can visualize haemodynamic and
      tissue changes after CPSE in the hippocampus, thalamus and affected cortical
      regions.

PMID- 15743872
TI  - Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis.
AB  - There are two distinct subtypes of multiple sclerosis in Asians, opticospinal (OS
      multiple sclerosis) and conventional (C-multiple sclerosis). In OS-multiple
      sclerosis, selective and severe involvement of the optic nerves and spinal cord
      is characteristic, though its mechanisms are unknown. The present study aimed to
      find out possible differences in the cytokine/chemokine profiles in CSF between
      OS-multiple sclerosis and C-multiple sclerosis and to delineate the relationships
      between these profiles and neuroimaging and pathological features. Sixteen
      cytokines/chemokines, namely interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL
      7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-gamma, tumour
      necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF),
      monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein
      1beta (MIP-1beta), were measured simultaneously in CSF supernatants from 40
      patients with relapsing-remitting multiple sclerosis (20 OS-multiple sclerosis
      and 20 C-multiple sclerosis) at relapse and 19 control patients with
      spinocerebellar degeneration (SCD), together with intracellular production of IFN
      gamma and IL-4 in CSF CD4+ T cells. In CSF supernatants relative to controls, IL
      17, MIP-1beta, IL-1beta and IL-13 were only significantly increased in OS
      multiple sclerosis patients, while TNF-alpha was only significantly increased in
      C-multiple sclerosis patients, using a cut-off level of 1 pg/ml. IL-8 was
      significantly elevated in both OS-multiple sclerosis and C-multiple sclerosis
      patients. MCP-1 was significantly decreased in both OS-multiple sclerosis and C
      multiple sclerosis patients, while IL-7 was only significantly decreased in C
      multiple sclerosis patients. IL-17, IL-8 and IL-5 were significantly higher in OS
      multiple sclerosis patients than in C-multiple sclerosis patients. The increases
      in IL-17 and IL-8 in OS-multiple sclerosis were still significant even after
      exclusion of the patients undergoing various immunomodulatory therapies. Assays
      of intracellular cytokine production revealed that both the IFN-gamma+IL-4- T
      cell percentage and intracellular IFN-gamma/IL-4 ratio in CSF cells were
      significantly greater in C-multiple sclerosis patients than in controls.
      Contrarily, OS-multiple sclerosis patients showed not only a significantly
      greater percentage of IFN-gamma+IL-4- T cells than controls but also a
      significantly higher percentage of IFN-gamma-IL-4+ T cells than C-multiple
      sclerosis patients. Among the cytokines elevated in multiple sclerosis, only IL-8
      showed a significant positive correlation with the Expanded Disability Status
      Scale of Kurtzke score. Both the length of the spinal cord lesions on MRI and the
      CSF/serum albumin ratio had a significant positive correlation with IL-8 and IL
      17 in multiple sclerosis, in which the spinal cord lesions were significantly
      longer in OS-multiple sclerosis than in C-multiple sclerosis. Three of six spinal
      cord specimens from autopsied OS-multiple sclerosis cases demonstrated numerous
      myeloperoxidase-positive neutrophils infiltrating necrotic lesions. These
      findings strongly suggest that in OS-multiple sclerosis, in addition to the Th1
      cell upregulation seen in C-multiple sclerosis, intrathecal activation of the IL
      17/IL-8 axis inducing heavy neutrophil infiltration contributes to extensive
      spinal cord lesion formation.

PMID- 15743873
TI  - Kinetic and kinematic workspaces of the index finger following stroke.
AB  - The objective of this study was to explore motor impairment of the index finger
      following stroke. More specifically, the kinetics and kinematics of the index
      finger were analysed throughout its workspace. Twenty-four stroke survivors with
      chronic hemiparesis of the hand participated in the trials, along with six age
      matched controls. Hand impairment was classified according to the clinical
      Chedoke-McMaster Stage of Hand scale. Subjects were instructed to generate
      fingertip force in six orthogonal directions at five different positions within
      the workspace. Split-plot analysis of variance revealed that clinical impairment
      level had a significant effect on measured force (P < 0.001), with the weakness
      in stroke survivors being directionally dependent (P < 0.01). Electromyographic
      recordings revealed altered muscle activation patterns in the more impaired
      subjects. Unlike the control subjects, these subjects exhibited peak muscle
      excitation of flexor digitorum superficialis, extensor digitorum communis and
      first dorsal interosseous during the generation of fingertip flexion forces.
      Subjects also attempted to reach locations scattered throughout the theoretical
      workspace of the index finger. Quantification of the active kinematic workspace
      demonstrated a relationship between impairment level and the percentage of the
      theoretical workspace that could be attained (P < 0.001). The stroke survivors
      exhibited a high correlation between mean force production and active workspace
      (R = 0.90). Thus, our data suggest that altered muscle activation patterns
      contribute to directionally dependent weakness following stroke. Both the
      modulation of muscle excitation with force direction and the independence of
      muscle activation seem to be reduced. These alterations translate into a
      significantly reduced active range of motion for the fingers.

PMID- 15743875
TI  - Black tea and cardiovascular disease.

PMID- 15743876
TI  - Clonal analysis of the relationships between mechanosensory cells and the neurons
      that innervate them in the chicken ear.
AB  - In vertebrates, hair-cell-bearing mechanosensory organs and the neurons that
      innervate them share a common placodal origin. In the inner ear, the peripheral
      neurons for both auditory and vestibular systems emigrate from the otic placode
      as neuroblasts, and divide, differentiate and innervate only one of six to eight
      distinct sensory organs. How these neurons find their correct target is unknown,
      although one suggestion is that they synapse with clonally related cells. To test
      this idea for both the middle and inner ears of chicken embryos, lineage analysis
      was initiated at the time of neuroblast delamination by labeling progenitors with
      replication-defective retroviruses. The vast majority (89%) of clones were
      restricted to a single anatomical subdivision of the sensory periphery or its
      associated ganglia, indicating limited clonal dispersion. Among the remaining
      clones, we found evidence of a shared neurosensory lineage in the middle ear.
      Likewise, in the inner ear, neurons could be related to cells of the otic
      epithelium, although the latter cells were not widely distributed. Rather, they
      were restricted to a region in or near the utricular macula. None of the other
      seven sensory organs was related to the ganglion neurons, suggesting that a
      common lineage between neurons and their targets is not a general mechanism of
      establishing synaptic connections in the inner ear. This conclusion is further
      strengthened by finding a shared lineage between the vestibular and acoustic
      ganglia, revealing the presence of a common progenitor for the two functional
      classes of neurons.

PMID- 15743877
TI  - Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a
      link between the PAR/aPKC complex and phosphoinositide signaling.
AB  - Cell polarity in Drosophila epithelia, oocytes and neuroblasts is controlled by
      the evolutionarily conserved PAR/aPKC complex, which consists of the serine
      threonine protein kinase aPKC and the PDZ-domain proteins Bazooka (Baz) and PAR
      6. The PAR/aPKC complex is required for the separation of apical and basolateral
      plasma membrane domains, for the asymmetric localization of cell fate
      determinants and for the proper orientation of the mitotic spindle. How the
      complex exerts these different functions is not known. We show that the lipid
      phosphatase PTEN directly binds to Baz in vitro and in vivo, and colocalizes with
      Baz in the apical cortex of epithelia and neuroblasts. PTEN is an important
      regulator of phosphoinositide turnover that antagonizes the activity of PI3
      kinase. We show that Pten mutant ovaries and embryos lacking maternal and zygotic
      Pten function display phenotypes consistent with a function for PTEN in the
      organization of the actin cytoskeleton. In freshly laid eggs, the germ plasm
      determinants oskar mRNA and Vasa are not localized properly to the posterior
      cytocortex and pole cells do not form. In addition, the actin-dependent posterior
      movement of nuclei during early cleavage divisions does not occur and the
      synchrony of nuclear divisions at syncytial blastoderm stages is lost. Pten
      mutant embryos also show severe defects during cellularization. Our data provide
      evidence for a link between the PAR/aPKC complex, the actin cytoskeleton and PI3
      kinase signaling mediated by PTEN.

PMID- 15743878
TI  - VAN3 ARF-GAP-mediated vesicle transport is involved in leaf vascular network
      formation.
AB  - Within the leaf of an angiosperm, the vascular system is constructed in a complex
      network pattern called venation. The formation of this vein pattern has been
      widely studied as a paradigm of tissue pattern formation in plants. To elucidate
      the molecular mechanism controlling the vein patterning process, we previously
      isolated Arabidopsis mutants van1 to van7, which show a discontinuous vein
      pattern. Here we report the phenotypic analysis of the van3 mutant in relation to
      auxin signaling and polar transport, and the molecular characterization of the
      VAN3 gene and protein. Double mutant analyses with pin1, emb30-7/gn and mp, and
      physiological analyses using the auxin-inducible marker DR5::GUS and an auxin
      transport inhibitor indicated that VAN3 may be involved in auxin signal
      transduction, but not in polar auxin transport. Positional cloning identified
      VAN3 as a gene that encodes an adenosine diphosphate (ADP)-ribosylation factor
      guanosine triphosphatase (GTPase) activating protein (ARF-GAP). It resembles
      animal ACAPs and contains four domains: a BAR (BIN/amphiphysin/RVS) domain, a
      pleckstrin homology (PH) domain, an ARF-GAP domain and an ankyrin (ANK)-repeat
      domain. Recombinant VAN3 protein showed GTPase-activating activity and a specific
      affinity for phosphatidylinositols. This protein can self-associate through the N
      terminal BAR domain in the yeast two-hybrid system. Subcellular localization
      analysis by double staining for Venus-tagged VAN3 and several green-fluorescent
      protein-tagged intracellular markers indicated that VAN3 is located in a
      subpopulation of the trans-Golgi network (TGN). Our results indicate that the
      expression of this gene is induced by auxin and positively regulated by VAN3
      itself, and that a specific ACAP type of ARF-GAP functions in vein pattern
      formation by regulating auxin signaling via a TGN-mediated vesicle transport
      system.

PMID- 15743879
TI  - Diversification of gene function: homologs of the floral regulator FLO/LFY
      control the first zygotic cell division in the moss Physcomitrella patens.
AB  - After fertilization, the zygote undergoes dynamic changes in chromosomal and
      cytoplasmic organization, and begins the cell cycles that eventually lead to
      formation of the multicellular embryo. Specific transcription factors that
      initiate this cascade of events in land plants have not been identified. We have
      identified two FLO/LFY genes, PpLFY1 and PpLFY2, that regulate the first cell
      division after formation of the zygote in the moss Physcomitrella patens. The
      deduced amino acid sequences of the two PpLFY genes are 94.8% identical to each
      other and show similar expression patterns. While fertilization occurred in the
      PpLFY disruptants, the development of double disruptant zygotes was arrested at
      the single-cell stage. When the double disruptants, as the female parent, were
      crossed with the wild type, as the male parent, normal sporophytes were formed,
      supporting the notion that the PpLFY genes function after fertilization to
      regulate the first mitotic cell division in zygotes. The rare sporophytes that
      formed on the PpLFY double disruptants showed mostly normal organogenesis, but
      had abnormalities in the pattern of cell division, supporting a role of PpLFY
      genes in regulating cell division. The FLO/LFY genes in angiosperms are conserved
      master regulators of floral identity without any obvious effects on cell
      division. By contrast, our study suggests that FLO/LFY genes have functions
      throughout sporophyte development in the basal land plant lineages.

PMID- 15743880
TI  - Making very similar embryos with divergent genomes: conservation of regulatory
      mechanisms of Otx between the ascidians Halocynthia roretzi and Ciona
      intestinalis.
AB  - Ascidian embryos develop with a fixed cell lineage into simple tadpoles. Their
      lineage is almost perfectly conserved, even between the evolutionarily distant
      species Halocynthia roretzi and Ciona intestinalis, which show no detectable
      sequence conservation in the non-coding regions of studied orthologous genes. To
      address how a common developmental program can be maintained without detectable
      cis-regulatory sequence conservation, we compared in both species the regulation
      of Otx, a gene with a shared complex expression pattern. We found that in
      Halocynthia, the regulatory logic is based on the use of very simple cell line
      specific regulatory modules, the activities of which are conserved, in most
      cases, in the Ciona embryo. The activity of each of these enhancer modules relies
      on the conservation of a few repeated crucial binding sites for transcriptional
      activators, without obvious constraints on their precise number, order or
      orientation, or on the surrounding sequences. We propose that a combination of
      simplicity and degeneracy allows the conservation of the regulatory logic,
      despite drastic sequence divergence. The regulation of Otx in the anterior
      endoderm by Lhx and Fox factors may even be conserved with vertebrates.

PMID- 15743881
TI  - NF-kappaB signalling regulates the growth of neural processes in the developing
      PNS and CNS.
AB  - The proper growth and elaboration of neural processes is essential for the
      establishment of a functional nervous system during development and is an
      integral feature of neural plasticity throughout life. Nuclear factor-kappa B (NF
      kappaB) is classically known for its ubiquitous roles in inflammation, immune and
      stress-related responses and regulation of cell survival in all tissues,
      including the nervous system. NF-kappaB participation in other cellular processes
      remains poorly understood. Here we report a mechanism for controlling the growth
      of neural processes in developing peripheral and central neurons involving the
      transcription factor NF-kappaB. Inhibiting NF-kappaB activation with super
      repressor IkappaB-alpha, BAY 11 7082 (IkappaB-alpha phosphorylation inhibitor) or
      N-acetyl-Leu-Leu-norleucinal (proteosomal degradation inhibitor), or inhibiting
      NF-kappaB transcriptional activity with kappaB decoy DNA substantially reduced
      the size and complexity of the neurite arbors of sensory neurons cultured with
      brain-derived neurotrophic factor while having no effect on their survival. NF
      kappaB exerted this effect during a restricted period of development following
      the phase of naturally occurring neuronal death when the processes and
      connections of the remaining neurons are extensively modified and refined.
      Inhibiting NF-kappaB activation or NF-kappaB transcriptional activity in layer 2
      pyramidal neurons in postnatal somatosensory cortical slices reduced dendritic
      arbor size and complexity. This function of NF-kappaB has important implications
      for neural development and may provide an explanation for reported involvement of
      NF-kappaB in learning and memory.

PMID- 15743882
TI  - The use of clinical guidelines for asthma, diabetes, and hypertension in primary
      health care.
AB  - OBJECTIVE: To investigate which clinical guidelines primary health care staff
      refer to regarding asthma, diabetes, and hypertension, the number of existing
      guidelines, and the organizational level at which they were drawn up, and whether
      there are different guidelines for the same disease, either in different primary
      health care centres or within individual centres. DESIGN: The study is
      descriptive. Data were obtained by telephone interviews and by procuring clinical
      guidelines regarding asthma, diabetes, and hypertension from primary health care
      centres. SETTING: Forty-one primary health care centres in one county in
      southeastern Sweden. STUDY PARTICIPANTS: General practitioners and registered
      nurses in primary health care. RESULTS: The telephone interviews showed that the
      staff referred to several guidelines covering each of the three diseases and
      these guidelines had been drawn up at five different organizational levels. The
      length of the clinical guidelines varied from 1 to 257 pages, and the number of
      guidelines for each disease ranged between 1 and 5. CONCLUSION: It was found that
      there were several documents covering the same disease that primary care staff
      referred to as 'guidelines', and that the length of the guidelines varied and
      they had been drawn up at different levels. A finding with possible serious
      consequences was that an old version of an asthma guideline was used in all
      primary health care centres in the study.

PMID- 15743883
TI  - A systematic review of appraisal tools for clinical practice guidelines: multiple
      similarities and one common deficit.
AB  - OBJECTIVE: To identify a critical appraisal tool for clinical practice guidelines
      that could serve as a basis for the development of an appraisal tool for clinical
      pathways. DESIGN: Systematic review of the literature and personal contacts.
      Databases searched were: Medline, Embase, and Cinahl. Search terms were: practice
      guidelines, appraisal, and evaluation. The items of the identified appraisal
      tools were examined and thematically grouped into 10 guideline dimensions.
      Content analysis and scoring of these domains by the appraisal tools was
      evaluated. RESULTS: Twenty-four different appraisal tools of practice guidelines
      were identified. None scored the evidence base of the clinical content of
      guidelines. Four tools scored all the guideline dimensions. The Cluzeau
      instrument is the only one of these four that has been validated. Of the three
      instruments based on the Cluzeau instrument, the AGREE instrument is the only
      validated instrument that uses a numerical scale. CONCLUSIONS: Being a simplified
      version of the Cluzeau instrument, the AGREE instrument has the most potential to
      serve as a basis for the development of an appraisal tool for clinical pathways.
      However, important limitations will have to be dealt with when developing such a
      tool.

PMID- 15743884
TI  - Local coordination verses systemic disregulation: complexities in leukocyte
      recruitment revealed by local and systemic activation of TLR4 in vivo.
AB  - The recruitment of leukocytes to a tissue is a critical step in the inflammatory
      response. Toll-like receptor 4 (TLR4) is an important receptor involved in the
      initiation of inflammatory responses. Administration of the ligand for TLR4,
      lipopolysaccharide, is often used to model inflammation--local responses to
      stimuli within a specific tissue and systemic responses such as those observed
      during endotoxic or septic shock. Here, we review work, which demonstrates that
      in response to local activation of TLR4, highly coordinated and multistep
      processes are initiated, ultimately resulting in the leukocyte's arrival at the
      inflamed tissue. In contrast, systemic activation of TLR4 results in nonspecific
      accumulation of leukocytes within the lung capillaries and liver sinusoids
      through mechanisms profoundly different than those involved in local tissue
      recruitment. Contrary to current dogma, leukocyte accumulation in the lung is
      dependent on endothelial rather than leukocyte activation. Finally, we discuss
      recent evidence suggesting that activation of leukocytes through TLR4, although
      still in the circulation, effectively paralyzes inflammatory cells, rendering
      them incapable of appropriate trafficking to inflamed tissues.

PMID- 15743885
TI  - Myosin lever disposition during length oscillations when power stroke tilting is
      reduced.
AB  - M3 reflection intensity (I(M3)) from tetanized, intact skeletal muscle fiber
      bundles was measured during sinusoidal length oscillations at 2.8 kHz, a
      frequency at which the myosin motor's power stroke is greatly reduced. I(M3)
      signals were approximately sinusoidal, but showed a "double peak" distortion
      previously observed only at lower oscillation frequencies. A tilting lever arm
      model simulated this distortion, where I(M3) was calculated from the molecular
      structure of myosin subfragment 1 (S1). Simulations showed an isometric lever arm
      disposition close to normal to the filament axis at isometric tension, similar to
      that found using lower oscillation frequencies, where the power stroke
      contributes more toward total S1 movement. Inclusion of a second detached S1 in
      each actin-bound myosin dimer increased simulated I(M3) signal amplitude and
      improved agreement with the experimental data. The best agreement was obtained
      when detached heads have a fixed orientation, insensitive to length changes, and
      similar to that of attached heads at tetanus plateau. This configuration also
      accounts for the variations in relative intensity of the two main peaks of the M3
      reflection substructure after a length change. This evidence of an I(M3) signal
      distortion when power stroke tilting is suppressed, provided that a large enough
      amplitude of length oscillation is used, is consistent with the tilting lever arm
      model of the power stroke.

PMID- 15743886
TI  - Effects of lactic acid and catecholamines on contractility in fast-twitch muscles
      exposed to hyperkalemia.
AB  - Intensive exercise is associated with a pronounced increase in extracellular K+
      ([K+]o). Because of the ensuing depolarization and loss of excitability, this
      contributes to muscle fatigue. Intensive exercise also increases the level of
      circulating catecholamines and lactic acid, which both have been shown to
      alleviate the depressing effect of hyperkalemia in slow-twitch muscles. Because
      of their larger exercise-induced loss of K+, fast-twitch muscles are more prone
      to fatigue caused by increased [K+]o than slow-twitch muscles. Fast-twitch
      muscles also produce more lactic acid. We therefore compared the effects of
      catecholamines and lactic acid on the maintenance of contractility in rat fast
      twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) muscles. Intact
      muscles were mounted on force transducers and stimulated electrically to evoke
      short isometric tetani. Elevated [K+]o (11 and 13 mM) was used to reduce force to
      approximately 20% of control force at 4 mM K+. In EDL, the beta2-agonist
      salbutamol (10(-5) M) restored tetanic force to 83 +/- 2% of control force,
      whereas in soleus salbutamol restored tetanic force to 93 +/- 1%. In both
      muscles, salbutamol induced hyperpolarization (5-8 mV), reduced intracellular Na+
      content and increased Na+-K+ pump activity, leading to an increased K+ tolerance.
      Lactic acid (24 mM) restored force from 22 +/- 4% to 58 +/- 2% of control force
      in EDL, an effect that was significantly lower than in soleus muscle. These
      results amplify and generalize the concept that the exercise-induced
      acidification and increase in plasma catecholamines counterbalance fatigue
      arising from rundown of Na+ and K+ gradients.

PMID- 15743887
TI  - Functional consequences of progressive cone dystrophy-associated mutations in the
      human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit.
AB  - Progressive cone dystrophies are a genetically heterogeneous group of disorders
      characterized by early deterioration of visual acuity and color vision, together
      with psychophysical and electrophysiological evidence of abnormal cone function
      and cone degeneration. Recently, three mutations in the gene encoding the CNGA3
      subunit of cone photoreceptor cyclic nucleotide-gated (CNG) channels have been
      linked to progressive cone dystrophy in humans. To investigate the functional
      consequences of these mutations, we expressed mutant human CNGA3 subunits in
      Xenopus oocytes, alone or together with human CNGB3, and studied these channels
      using patch-clamp recording. Compared with wild-type channels, homomeric and
      heteromeric channels containing CNGA3-N471S or CNGA3-R563H subunits exhibited an
      increase in apparent affinity for cGMP and an increase in the relative agonist
      efficacy of cAMP compared with cGMP. In contrast, R277C subunits did not form
      functional homomeric or heteromeric channels. Cell surface expression levels,
      determined using confocal microscopy of green fluorescent protein-tagged subunits
      and patch-clamp recording, were significantly reduced for both R563H and R277C
      but unchanged for N471S. Overall, these results suggest that the plasma membrane
      localization and gating properties of cone CNG channels are altered by
      progressive cone dystrophy-associated mutations, providing evidence that supports
      the pathogenicity of these mutations.

PMID- 15743888
TI  - Involvement of poly(ADP-ribose) polymerase 1 in ERBB2 expression in rheumatoid
      synovial cells.
AB  - Hyperplasia of synovial lining cells is one of the main features of rheumatoid
      arthritis (RA). We previously reported that ERBB2 is highly expressed in RA
      synovial cells and that it plays an important role in their hyperproliferative
      growth. Recent findings have suggested that poly(ADP-ribose) polymerase-1 (PARP
      1) is involved in the transactivation of NF-kappaB-dependent genes such as ERBB2.
      In the present study, we investigated the role of PARP-1 in ERBB2 transcription
      in RA synovial cells. The expression level of PARP-1 was significantly high in
      synovial cells derived from three patients with RA, compared with three patients
      with osteoarthritis (OA). Luciferase assays revealed that PARP-1 augments the
      transcription of the ERBB2 gene and that a region between -404 and -368 is
      responsible for this activation. A protein with an apparent molecular mass of 115
      kDa was isolated mainly from nuclear extracts of RA synovial cells with an
      affinity matrix harboring a DNA fragment identical to the above region. Mass
      spectrometric analysis demonstrated this protein to be PARP-1. Southwestern blot
      analysis showed that PARP-1 binds to this region, but not to adjacent regions.
      PARP-1 associates directly with NF-kappaB, and a chromatin immunoprecipitation
      assay indicated that these proteins interact with this enhancer region in the
      ERBB2 gene. Treatment of RA synovial cells with PARP-1 small interfering RNA
      attenuated their ERBB2 expression, while an inhibitor of the polymerase activity
      of PARP-1 had no effect. PARP-1 DNA binding is not required for transcriptional
      activation. These findings suggest that PARP-1 is involved in the expression of
      ERBB2 in concert with NF-kappaB, which might be associated with the proliferation
      of RA synovial cells.

PMID- 15743889
TI  - Mechanism of amyloid peptide induced CCR5 expression in monocytes and its
      inhibition by siRNA for Egr-1.
AB  - In Alzheimer's disease (AD), one finds increased presence of
      monocytes/macrophages and activated microglial cells in the brain.
      Immunohistochemical studies show increased expression of chemokine receptor 5
      (CCR5) on reactive microglia associated with amyloid deposits in AD, suggesting
      that CCR5 may play a role in the regulation of the immune response in AD. In this
      study, we used peripheral blood monocytes and human monocytic THP-1 cell line as
      a model of microglia to delineate the cellular signaling mechanism of Abeta
      induced CCR5 expression and the latter's role in the chemotaxis of monocytes. We
      observed that Abeta peptides at pathophysiological concentrations (125 nM)
      increased CCR5 mRNA and cell surface protein expression. The cellular signaling
      involved activation of c-Raf, ERK-1/ERK-2, and c-Jun NH(2)-terminal kinase.
      Analysis of some transcription factors associated with CCR5 promoter revealed
      that Abeta increased DNA binding activity of Egr-1 and AP-1. In addition, we show
      that CCR5 promoter contains an Egr-1 like consensus sequence GCGGGGGTG as
      demonstrated by 1) electrophoretic mobility shift assay, 2) transfection studies
      with truncated CCR5 gene promoter construct, and 3) chromatin immunoprecipitation
      analysis. Moreover, transfection of Egr-1 siRNA, but not of scrambled Egr-1
      siRNA, in THP-1 cells resulted in >75% reduction in both Abeta-mediated CCR5
      expression and concomitant chemotaxis to its ligands. We suggest that inhibition
      of Egr-1 by either Egr-1 siRNA or pharmacological agents may reduce activation of
      monocytes/microglia and possibly ameliorate the inflammation and progression of
      AD.

PMID- 15743890
TI  - A role for Rho and Rac in secretagogue-induced amylase release by pancreatic
      acini.
AB  - The actin cytoskeleton has long been implicated in protein secretion. We
      investigated whether Rho and Rac, known regulators of the cytoskeleton, are
      involved in amylase secretion by mouse pancreatic acini. Secretagogues, including
      cholecystokinin (CCK) and the acetylcholine analog carbachol, increased the
      amount of GTP-bound RhoA and Rac1 and induced translocation from cytosol to a
      membrane fraction. Immunocytochemistry revealed the translocation of Rho and Rac
      within the apical region of the cell. Expression by means of adenoviral vectors
      of dominant-negative Rho (RhoN19), dominant-negative Rac (RacN17), and
      Clostridium Botulinum C3 exotoxin, which ADP ribosylates and inactivates Rho,
      significantly inhibited amylase secretion by CCK and carbachol; inhibiting both
      Rho and Rac resulted in a greater reduction. This inhibitory effect of RhoN19 on
      CCK-induced amylase secretion was apparent in both the early and late phases of
      secretion, whereas RacN17 was more potent on the late phase of secretion. None of
      these three affected the basal Ca2+ or the peak intracellular Ca2+ concentration
      stimulated by CCK. Latrunculin, a marine toxin that sequesters actin monomers,
      time-dependently decreased the total amount of filamentous actin (F-actin) and
      dose-dependently decreased secretion by secretagogues without affecting Ca2+
      signaling. These data suggest that Rho and Rac are both involved in CCK-induced
      amylase release in pancreatic acinar cell possibly through an effect on the actin
      cytoskeleton.

PMID- 15743891
TI  - Intermediate-conductance Ca2+-activated K+ channel is expressed in C2C12
      myoblasts and is downregulated during myogenesis.
AB  - We report here the expression in C2C12 myoblasts of the intermediate-conductance
      Ca2+-activated K+ (IK(Ca)) channel. The IK(Ca) current, recorded under perforated
      patch configuration, had a transient time course when activated by ionomycin (0.5
      microM; peak current density 26.2 +/- 3.7 pA/pF; n = 10), but ionomycin (0.5
      microM) + 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (100 microM)
      evoked a stable outward current (28.4 +/- 8.2 pA/pF; n = 11). The current was
      fully inhibited by charybdotoxin (200 nM), clotrimazole (2 microM), and 5-nitro-2
      (3-phenylpropylamino)benzoic acid (300 microM), but not by tetraethylammonium (1
      mM) or D-tubocurarine (300 microM). Congruent with the IK(Ca) channel, elevation
      of intracellular Ca2+ in inside-out patches resulted in the activation of a
      voltage-insensitive K+ channel with weak inward rectification, a unitary
      conductance of 38 +/- 6 pS (at negative voltages), and an IC50 for Ca2+ of 530
      nM. The IK(Ca) channel was activated metabotropically by external application of
      ATP (100 microM), an intracellular Ca2+ mobilizer. Under current-clamp
      conditions, ATP application resulted in a membrane hyperpolarization of
      approximately 35 mV. The IK(Ca) current downregulated during myogenesis, ceasing
      to be detectable 4 days after the myoblasts were placed in differentiating
      medium. Downregulation was prevented by the myogenic suppressor agent basic FGF
      (bFGF). We also found that block of the IK(Ca) channel by charybdotoxin did not
      inhibit bFGF-sustained myoblast proliferation. These observations show that in
      C2C12 myoblasts the IK(Ca) channel expression correlates inversely with
      differentiation, yet it does not appear to have a role in myoblast proliferation.

PMID- 15743892
TI  - Lower force and impaired performance during high-intensity electrical stimulation
      in skeletal muscle of GAMT-deficient knockout mice.
AB  - Force characteristics of skeletal muscle of knockout mice lacking creatine (Cr)
      due to a deletion of guanidinoacetate methyltransferase (GAMT) were studied in
      situ. Medial gastrocnemius muscles of anesthetized GAMT-deficient (GAMT-/-) and
      control (Con) littermates were stimulated at optimum length via the sciatic nerve
      at different stimulation frequencies (60-250 Hz). GAMT-/- mice showed reduced
      maximal tetanic and twitch force, reduced relative force at 60 Hz, and increased
      relaxation times. High-intensity fatigue protocols consisting of 30 successive
      isometric or dynamic contractions showed a strong reduction in force at the
      beginning of the series in GAMT-/- mice, followed by a smaller reduction compared
      with Con littermates toward the end of the series. Cr supplementation for 2 days
      in GAMT-/- animals (GAMT(Cr)-/-) resulted in normalization to Con values for
      relaxation times, relative force at lower stimulation frequencies, and relative
      force during 30 isometric contractions. Force per muscle mass, however, remained
      decreased. Furthermore,GAMT(Cr)-/- mice showed differences compared with both Con
      and unsupplemented animals in maximal rates of force rise and relaxation times
      during the isometric protocol as well as in force during the dynamic protocol.
      Our results show that the absence of Cr plays a direct role in relaxation times,
      maximal rate of force rise, and force production during high-intensity fatigue
      protocols. The lower force per muscle mass, however, is probably caused by other
      factors; i.e., high intracellular guanidinoacetate concentrations.

PMID- 15743894
TI  - Severe myopathy and possible hepatotoxicity related to daptomycin.

PMID- 15743893
TI  - Successful treatment with linezolid of septic shock secondary to methicillin
      resistant Staphylococcus aureus arthritis.

PMID- 15743895
TI  - Prospects for adenovirus antivirals.
AB  - Adenoviruses cause a number of self-limiting but often highly infectious diseases
      that affect multiple organs, most commonly those associated with respiratory,
      genitourinary and gastrointestinal tracts and the ocular surface. Many factors
      have driven a search for effective topical and systemic antivirals to
      adenoviruses. These include patient morbidity, economic losses and chronic visual
      disturbances associated with epidemic keratoconjunctivitis; and the startling
      recent trend of high morbidity and rising mortality associated with systemic
      adenoviral infections in the immunosuppressed, particularly paediatric bone
      marrow transplant recipients. The development of effective antivirals has proven
      to be a complex task, owing to the fact that multiple and often genetically
      divergent adenovirus serotypes can cause similar diseases. Currently, there
      remains no licensed systemic or topical treatment in the USA or Europe. However,
      many compounds have been explored for activity against adenoviruses, and some
      have been evaluated clinically in either a topical setting for ocular disease or
      in the setting of systemic treatment in the face of life-threatening adenovirus
      infections. This article outlines such compounds, discusses the potential for
      their clinical development, and highlights some problems that may be faced in
      evaluating their efficacy clinically.

PMID- 15743896
TI  - Topical microbicides for the prevention of genital herpes infection.
AB  - Genital herpes is one of the most prevalent sexually transmitted infections
      worldwide and is the most common cause of genital ulcers. Despite increased
      public awareness and the initiation of efforts to prevent transmission, the
      prevalence of herpes simplex virus (HSV) type 2 continues to increase. What makes
      HSV so difficult to control is that most sexual and perinatal transmission occurs
      during unrecognized or asymptomatic shedding. The impact of genital herpes as a
      public health threat is amplified because of its epidemiological synergy with
      HIV/AIDS. Thus, there is an urgent need for novel prophylactic methods, such as
      topical microbicides designed for genital application, to prevent both HSV and
      HIV transmission. Several candidate microbicides are being advanced to clinical
      trials based on in vitro activity and animal studies. These include compounds
      that inactivate virus directly, those that enhance innate immunity, and drugs
      that block viral binding and entry. A more vigorous evaluation of the safety of
      these and other candidate topical microbicides in development should include
      assessment of the impact of repeated application on innate host defences in the
      genital tract.

PMID- 15743897
TI  - Novel [(biphenyloxy)propyl]isoxazole derivatives for inhibition of human
      rhinovirus 2 and coxsackievirus B3 replication.
AB  - OBJECTIVES: During this study, novel biphenyl derivatives were synthesized and
      tested for antiviral activity. METHODS: A new method based on the Suzuki coupling
      reaction has been established for the synthesis of these polysubstituted chain
      systems. In parallel with cytotoxicity, the antiviral activity of biphenyl
      derivatives has been determined in cytopathic effect (CPE)-inhibitory assays with
      the pleconaril-resistant coxsackievirus B3 (CVB3) strain Nancy, human rhinovirus
      2 (HRV-2) and 14 (HRV-14) and in plaque reduction assays with the pleconaril
      sensitive human isolate CVB3 97-927 in HeLa cells. Based on the results from
      these investigations the selectivity index (SI) was determined as the ratio of
      the 50% cytotoxic concentration to the 50% inhibitory concentration. RESULTS: The
      new method based on the Suzuki coupling reaction includes the condensation of 2,6
      dimethyl-4-bromophenol with pentyne chloride by means of potassium carbonate and
      potassium iodide in N-methylpyrrolidone-2 and yields 5-bromo-1,3-dimethyl-2-(4
      pentynyloxy)benzene. Its condensation with methylacetaldoxime results in 3
      methylisoxazole derivatives. The following reaction with different benzeneboronic
      acids by means of tetrakis(triphenylphosphine)-palladium(0) finally yields the
      corresponding derivatives. Several of the novel synthesized derivatives
      demonstrated a good antiviral activity on CVB3 (SI > 2 to > 37.5) and a strong
      anti-HRV-2 activity (SI > 50 to > 200). In contrast, none of the compounds
      inhibited the HRV-14-induced CPE. CONCLUSIONS: These results indicate that
      [(biphenyloxy)propyl]isoxazole derivatives are potential inhibitors of HRV-2 and
      CVB3 replication, and make them promising agents for the specific treatment of
      these virus infections.

PMID- 15743898
TI  - Monitoring in vivo fitness of rifampicin-resistant Staphylococcus aureus mutants
      in a mouse biofilm infection model.
AB  - OBJECTIVES: To investigate in vivo fitness of rifampicin-resistant Staphylococcus
      aureus mutants in a mouse biofilm model using bioluminescence imaging. MATERIALS
      AND METHODS: S. aureus was engineered with a luciferase operon to emit
      bioluminescence that can be detected in vivo using an IVIS imaging system. Two
      rifampicin-resistant strains of S. aureus that were previously isolated from
      animals undergoing rifampicin treatment, S464P (resistant to low concentrations
      of rifampicin) and H481Y (resistant to high concentrations of rifampicin), were
      characterized and then compared with their parental strain for in vivo fitness to
      form biofilm infections in the absence of rifampicin. RESULTS: The mutant S464P
      showed better adaptation to in vivo growth than either the parental strain or
      H481Y without selective pressure. Six days after implanting pre-colonized
      catheters, bioluminescent signals were seen from 100% of the catheters coated by
      the mutant S464P. In comparison, only 83% and 61% of the catheters coated by the
      parental strain and H481Y, respectively, maintained a signal in vivo. Rifampicin
      treatment of S464P biofilms in vivo resulted in a slight decline, but earlier
      rebound in bioluminescence from these catheters compared with the parental
      signal, whereas rifampicin had no affect on bioluminescence in mice infected with
      mutant H481Y. CONCLUSIONS: The mutant with low-level rifampicin resistance
      appears to be better adapted to in vivo growth than the mutant that has high
      level rifampicin resistance. Moreover, the former mutant may actually have a
      slight competitive advantage over the rifampicin-susceptible strain (parental),
      raising awareness for the occurrence of such strains in clinical environments.

PMID- 15743899
TI  - Cefoxitin resistance as a surrogate marker for the detection of methicillin
      resistant Staphylococcus aureus.
AB  - OBJECTIVES: To evaluate the usefulness of cefoxitin when used as a surrogate
      marker for the detection of methicillin resistance. PATIENTS AND METHODS: Eight
      hundred and seventy-one strains of Staphylococcus aureus, collected from eight
      tertiary referral centres serving diverse socio-economic populations, were
      included in the study using NCCLS disc diffusion and the agar dilution methods.
      RESULTS: Using cefoxitin and NCCLS criteria for disc diffusion, the sensitivity
      and specificity for recognizing methicillin resistance were both 100%. Similar
      results were obtained when the strains were tested by the agar dilution method.
      The cefoxitin MICs for methicillin-susceptible strains were < or = 4 mg/L.
      CONCLUSIONS: Testing with cefoxitin as a surrogate marker for the detection of
      methicillin resistance was very accurate with both disc diffusion and agar
      dilution methods. Such testing clearly distinguished methicillin-resistant
      strains of S. aureus from methicillin-susceptible strains.

PMID- 15743900
TI  - Tetracycline resistance of Australian Campylobacter jejuni and Campylobacter coli
      isolates.
AB  - OBJECTIVES: Tetracycline resistance in Campylobacter is encoded by the tet(O)
      gene and is usually associated with conjugative plasmids. Little was known about
      tetracycline resistance in Australian Campylobacter species, therefore we
      investigated this resistance in 41 Campylobacter jejuni and five Campylobacter
      coli strains from humans and healthy chickens. METHODS: Tetracycline MICs were
      determined for each isolate using an agar dilution method. The distribution and
      localization of tet(O) on plasmid and chromosomal DNA was determined by Southern
      blot experiments. The ability to transfer resistance to recipient strains was
      examined through conjugation studies. Identity of transconjugants was confirmed
      by PCR and flaA-restriction fragment length polymorphism analysis. RESULTS: High
      level tetracycline resistance was observed, ranging from 32 to >256 mg/L.
      Plasmids were detected in 74% of isolates with plasmids between 30 and 40 kb in
      size most frequently isolated. tet(O) was present in all tetracycline-resistant
      isolates. In the majority of strains under study the tet(O) gene was
      chromosomally encoded. Tetracycline resistance of six C. jejuni strains in which
      tet(O) was plasmid mediated was transferred by conjugation to a C. jejuni
      recipient strain. Transfer did not occur between tetracycline-resistant C. jejuni
      strains and a C. coli recipient. No difference in MICs, plasmid carriage and
      tet(O) localization was detected between human and chicken isolates. CONCLUSIONS:
      These data indicate that the tet(O) gene, previously reported in Campylobacter
      strains throughout the world, is present in Australian Campylobacter. This study
      will lead to a greater understanding of antibiotic resistance distribution in
      Campylobacter spp. in Australia.

PMID- 15743901
TI  - Description of In116, the first blaCTX-M-2-containing complex class 1 integron
      found in Morganella morganii isolates from Buenos Aires, Argentina.
AB  - OBJECTIVES: We analysed the architecture and probable origin of a class 1
      integron from cefotaxime-resistant Morganella morganii isolates. METHODS: bla
      genes and class 1 integron elements were detected by PCR and DNA-DNA
      hybridization in a M. morganii strain isolated in 1996. PCR-mapping and
      sequencing of different fragments were carried out to determine the integron's
      architecture. RESULTS AND CONCLUSIONS: A class 1 integron (In116), strongly
      related to the In6/In7 family, was detected in a plasmid from an oxyimino
      cephalosporin-resistant M. morganii strain, producing CTX-M-2 beta-lactamase. The
      variable region of In116 contains aacA4, bla(OXA-2) and orfD cassettes.
      Downstream of the 3'-conserved-segment (3'-CS), an orf513-containing common
      region is followed by bla(CTX-M-2) and flanking regions, having 96-99% nucleotide
      identity with Kluyvera ascorbata's kluA-1 and neighbouring sequences. Some of the
      evidence supporting the incorporation of foreign DNA is as follows: a partial
      deletion in a second 3'-CS (3'-CS2), and the absence of 59-base element or IS
      like structures upstream of bla(CTX-M-2).

PMID- 15743902
TI  - Assessing genetic diversity in clonal organisms: low diversity or low resolution?
      Combining power and cost efficiency in selecting markers.
AB  - The increasing use of molecular tools to study populations of clonal organisms
      leads us to question whether the low polymorphism found in many studies reflects
      limited genetic diversity in populations or the limitations of the markers used.
      Here we used microsatellite datasets for two sea grass species to provide a
      combinatory statistic, combined with a likelihood approach to estimate the
      probability of identical multilocus genotypes (MLGs) to be shared by distinct
      individuals, in order to ascertain the efficiency of the markers used and to
      optimize cost-efficiently the choice of markers to use for deriving unbiased
      estimates of genetic diversity. These results strongly indicate that conclusions
      from studies on clonal organisms derived using markers showing low polymorphism,
      including microsatellites, should be reassessed using appropriate polymorphic
      markers.

PMID- 15743903
TI  - Strong reproductive skew among males in the multiply mated swordtail Xiphophorus
      multilineatus (Teleostei).
AB  - Male swordtails in the genus Xiphophorus display a conspicuous ventral elongation
      of the caudal fin, the sword, which arose through sexual selection due to female
      preference. Females mate regularly and are able to store sperm for at least 6
      months. If multiple mating is frequent, this would raise the intriguing question
      about the role of female choice and male-male competition in shaping the mating
      system of these fishes. Size-dependent alternate mating strategies occur in
      Xiphophorus; one such strategy is courtship with a sigmoid display by large
      dominant males, while the other is gonopodial thrusting, in which small
      subordinate males sneak copulations. Using microsatellite markers, we observed a
      frequency of multiple paternity in wild-caught Xiphophorus multilineatus in 28%
      of families analyzed, but the actual frequency of multiple mating suggested by
      the correction factor PrDM was 33%. The number of fathers contributing
      genetically to the brood ranged from one to three. Compared to other species in
      the family Poeciliidae, both frequency and degree of multiple paternity were low.
      Paternity was found to be highly skewed, with one male on average contributing
      more than 70% to the offspring. Hence in this Xiphophorus mating system,
      typically one male dominates and sneaker males do not appear to be particularly
      effective. Postcopulatory mechanisms, however, such as sperm competition, are
      also indicated by our data, using sex-linked phenotypes among the offspring.

PMID- 15743904
TI  - Paternal effects on the defensive behavior of honeybees.
AB  - The defensive behavior of 52 hybrid honeybee (Apis mellifera L.) colonies from
      four sets of crosses was studied and compared with that of European and
      Africanized bee colonies. Colonies containing F(1) hybrid workers were obtained
      through reciprocal crosses between European and Africanized bees. The total
      number of stings deposited by workers in a moving leather patch in 1 min was
      recorded. In each of the four sets of crosses, bees from hybrid colonies of
      Africanized paternity left more stings in leather patches than bees from hybrid
      colonies of European paternity. Results strongly suggest paternal effects of
      African origin increasing the defensive behavior of hybrid colonies. Although
      some degree of dominance was observed for high-defensive behavior in one of the
      four sets of crosses involving European paternity, most of the dominance effects
      reported in the literature appear to be the result of paternal effects. Several
      hypotheses to explain this phenomenon, as well as the implications of these
      effects on the fitness and breeding of honeybees are discussed.

PMID- 15743905
TI  - Genetic screening for prey in the gut contents from a giant squid (Architeuthis
      sp.).
AB  - Giant squids (Architeuthis sp.) remain mysterious; they have evaded observation
      and are rarely taken from their deep sea habitat. Information on the diet of
      Architeuthis is scarce due to the limited number of specimens with
      morphologically recognizable remains in their digestive tracts. We explored the
      use of polymerase chain reaction (PCR)-based methods for detection of DNA in the
      prey remains and amorphous slurry from an Architeuthis gut sample. The DNA region
      amplified varied in size, allowing separation of fish and squid components.
      Sequence comparisons identified fish prey as Macruronus novaezelandiae. Isolation
      of Architeuthis DNA from an ingested tentacle and the presence of chitin
      fragments indicate cannibalism occurs in giant squid. Denaturing gradient gel
      electrophoresis was used to screen for less common DNA types, revealing a high
      frequency of PCR-generated false alleles, but no additional prey species.

PMID- 15743906
TI  - Neurabin/protein phosphatase-1 complex regulates dendritic spine morphogenesis
      and maturation.
AB  - The majority of excitatory synapses in the mammalian brain form on filopodia and
      spines, actin-rich membrane protrusions present on neuronal dendrites. The
      biochemical events that induce filopodia and remodel these structures into
      dendritic spines remain poorly understood. Here, we show that the neuronal actin-
      and protein phosphatase-1-binding protein, neurabin-I, promotes filopodia in
      neurons and nonneuronal cells. Neurabin-I actin-binding domain bundled F-actin,
      promoted filopodia, and delayed the maturation of dendritic spines in cultured
      hippocampal neurons. In contrast, dimerization of neurabin-I via C-terminal
      coiled-coil domains and association of protein phosphatase-1 (PP1) with neurabin
      I through a canonical KIXF motif inhibited filopodia. Furthermore, the expression
      of a neurabin-I polypeptide unable to bind PP1 delayed the maturation of neuronal
      filopodia into spines, reduced the synaptic targeting of AMPA-type glutamate
      (GluR1) receptors, and decreased AMPA receptor-mediated synaptic transmission.
      Reduction of endogenous neurabin levels by interference RNA (RNAi)-mediated
      knockdown also inhibited the surface expression of GluR1 receptors. Together, our
      studies suggested that disrupting the functions of a cytoskeletal neurabin/PP1
      complex enhanced filopodia and impaired surface GluR1 expression in hippocampal
      neurons, thereby hindering the morphological and functional maturation of
      dendritic spines.

PMID- 15743907
TI  - ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP
      localization but is dispensable for Chk1 phosphorylation.
AB  - ATR associates with the regulatory protein ATRIP that has been proposed to
      localize ATR to sites of DNA damage through an interaction with single-stranded
      DNA (ssDNA) coated with replication protein A (RPA). We tested this hypothesis
      and found that ATRIP is required for ATR accumulation at intranuclear foci
      induced by DNA damage. A domain at the N terminus of ATRIP is necessary and
      sufficient for interaction with RPA-ssDNA. Deletion of the ssDNA-RPA interaction
      domain of ATRIP greatly diminished accumulation of ATRIP into foci. However, the
      ATRIP-RPA-ssDNA interaction is not sufficient for ATRIP recognition of DNA
      damage. A splice variant of ATRIP that cannot bind to ATR revealed that ATR
      association is also essential for proper ATRIP localization. Furthermore, the
      ATRIP-RPA-ssDNA interaction is not absolutely essential for ATR activation
      because ATR phosphorylates Chk1 in cells expressing only a mutant of ATRIP that
      does not bind to RPA-ssDNA. These data suggest that binding to RPA-ssDNA is not
      the essential function of ATRIP in ATR-dependent checkpoint signaling and ATR has
      an important function in properly localizing the ATR-ATRIP complex.

PMID- 15743908
TI  - FXYD3 (Mat-8), a new regulator of Na,K-ATPase.
AB  - Four of the seven members of the FXYD protein family have been identified as
      specific regulators of Na,K-ATPase. In this study, we show that FXYD3, also known
      as Mat-8, is able to associate with and to modify the transport properties of
      Na,K-ATPase. In addition to this shared function, FXYD3 displays some uncommon
      characteristics. First, in contrast to other FXYD proteins, which were shown to
      be type I membrane proteins, FXYD3 may have a second transmembrane-like domain
      because of the presence of a noncleavable signal peptide. Second, FXYD3 can
      associate with Na,K- as well as H,K-ATPases when expressed in Xenopus oocytes.
      However, in situ (stomach), FXYD3 is associated only with Na,K-ATPase because its
      expression is restricted to mucous cells in which H,K-ATPase is absent.
      Coexpressed in Xenopus oocytes, FXYD3 modulates the glycosylation processing of
      the beta subunit of X,K-ATPase dependent on the presence of the signal peptide.
      Finally, FXYD3 decreases both the apparent affinity for Na+ and K+ of Na,K
      ATPase.

PMID- 15743911
TI  - "New approach" as Health Canada seeks conditional licences for drugs, new
      pediatric office.

PMID- 15743909
TI  - Profilin-mediated competition between capping protein and formin Cdc12p during
      cytokinesis in fission yeast.
AB  - Fission yeast capping protein SpCP is a heterodimer of two subunits (Acp1p and
      Acp2p) that binds actin filament barbed ends. Neither acp1 nor acp2 is required
      for viability, but cells lacking either or both subunits have cytokinesis defects
      under stressful conditions, including elevated temperature, osmotic stress, or in
      combination with numerous mild mutations in genes important for cytokinesis.
      Defects arise as the contractile ring constricts and disassembles, resulting in
      delays in cell separation. Genetic and biochemical interactions show that the
      cytokinesis formin Cdc12p competes with capping protein for actin filament barbed
      ends in cells. Deletion of acp2 partly suppresses cytokinesis defects in
      temperature-sensitive cdc12-112 cells and mild overexpression of capping protein
      kills cdc12-112 cells. Biochemically, profilin has opposite effects on filaments
      capped with Cdc12p and capping protein. Profilin depolymerizes actin filaments
      capped by capping protein but allows filaments capped by Cdc12p to grow at their
      barbed ends. Once associated with a barbed end, either Cdc12p or capping protein
      prevents the other from influencing polymerization at that end. Given that
      capping protein arrives at the division site 20 min later than Cdc12p, capping
      protein may slowly replace Cdc12p on filament barbed ends in preparation for
      filament disassembly during ring constriction.

PMID- 15743910
TI  - Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy.
AB  - In eukaryotic cells, nutrient starvation induces the bulk degradation of cellular
      materials; this process is called autophagy. In the yeast Saccharomyces
      cerevisiae, most of the ATG (autophagy) genes are involved in not only the
      process of degradative autophagy, but also a biosynthetic process, the cytoplasm
      to vacuole (Cvt) pathway. In contrast, the ATG17 gene is required specifically in
      autophagy. To better understand the function of Atg17, we have performed a
      biochemical characterization of the Atg17 protein. We found that the atg17delta
      mutant under starvation condition was largely impaired in autophagosome formation
      and only rarely contained small autophagosomes, whose size was less than one-half
      of normal autophagosomes in diameter. Two-hybrid analyses and
      coimmunoprecipitation experiments demonstrated that Atg17 physically associates
      with Atg1-Atg13 complex, and this binding was enhanced under starvation
      conditions. Atg17-Atg1 binding was not detected in atg13delta mutant cells,
      suggesting that Atg17 interacts with Atg1 through Atg13. A point mutant of Atg17,
      Atg17(C24R), showed reduced affinity for Atg13, resulting in impaired Atg1 kinase
      activity and significant defects in autophagy. Taken together, these results
      indicate that Atg17-Atg13 complex formation plays an important role in normal
      autophagosome formation via binding to and activating the Atg1 kinase.

PMID- 15743912
TI  - Dosanjh to act on Canada Health Act violations.

PMID- 15743913
TI  - Medroxyprogesterone acetate (Depo-Provera) and bone mineral density loss.

PMID- 15743914
TI  - Robust in vitro activity of RebF and RebH, a two-component reductase/halogenase,
      generating 7-chlorotryptophan during rebeccamycin biosynthesis.
AB  - The indolocarbazole antitumor agent rebeccamycin is modified by chlorine atoms on
      each of two indole moieties of the aglycone scaffold. These halogens are
      incorporated during the initial step of its biosynthesis from conversion of L-Trp
      to 7-chlorotryptophan. Two genes in the biosynthetic cluster, rebF and rebH, are
      predicted to encode the flavin reductase and halogenase components of an FADH2
      dependent halogenase, a class of enzymes involved in the biosynthesis of numerous
      halogenated natural products. Here, we report that, in the presence of O2,
      chloride ion, and L-Trp as cosubstrates, purified RebH displays robust
      regiospecific halogenating activity to generate 7-chlorotryptophan over at least
      50 catalytic cycles. Halogenation by RebH required the addition of RebF, which
      catalyzes the NADH-dependent reduction of FAD to provide FADH2 for the
      halogenase. Maximal rates were achieved at a RebF/RebH ratio of 3:1. In air
      saturated solutions, a k(cat) of 1.4 min(-1) was observed for the RebF/RebH
      system but increased at least 10-fold in low-pO2 conditions. RebH was also able
      to use bromide ions to generate monobrominated Trp. The demonstration of robust
      chlorinating activity by RebF/RebH sets up this system for the probing of
      mechanistic questions regarding this intriguing class of enzymes.

PMID- 15743915
TI  - High levels of catalytic antibodies correlate with favorable outcome in sepsis.
AB  - Sepsis is the leading cause of death in intensive care units and results from a
      deleterious systemic host response to infection. Although initially perceived as
      potentially deleterious, catalytic antibodies have been proposed to participate
      in removal of metabolic wastes and protection against infection. Here we show
      that the presence in plasma of IgG endowed with serine protease-like hydrolytic
      activity strongly correlates with survival from sepsis. Variances of catalytic
      rates of IgG were greater in the case of patients with severe sepsis than healthy
      donors (P < 0.001), indicating that sepsis is associated with alterations in
      plasma levels of hydrolytic IgG. The catalytic rates of IgG from patients who
      survived were significantly greater than those of IgG from deceased patients (P <
      0.05). The cumulative rate of survival was higher among patients exhibiting high
      rates of IgG-mediated hydrolysis as compared with patients with low hydrolytic
      rates (P < 0.05). An inverse correlation was also observed between the markers of
      severity of disseminated intravascular coagulation and rates of hydrolysis of
      patients' IgG. Furthermore, IgG from three surviving patients hydrolyzed factor
      VIII, one of which also hydrolyzed factor IX, suggesting that, in some patients,
      catalytic IgG may participate in the control of disseminated microvascular
      thrombosis. Our observations provide the first evidence that hydrolytic
      antibodies might play a role in recovery from a disease.

PMID- 15743916
TI  - Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15
      imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor.
AB  - We have analyzed several cases of Beckwith-Wiedemann syndrome (BWS) with Wilms'
      tumor in a familial setting, which give insight into the complex controls of
      imprinting and gene expression in the chromosome 11p15 region. We describe a 2.2
      kbp microdeletion in the H19/insulin-like growth factor 2 (IGF2)-imprinting
      center eliminating three target sites of the chromatin insulator protein CTCF
      that we believe here is necessary, but not sufficient, to cause BWS and Wilms'
      tumor. Maternal inheritance of the deletion is associated with IGF2 loss of
      imprinting and up-regulation of IGF2 mRNA. However, in at least one affected
      family member a second genetic lesion (a duplication of maternal 11p15) was
      identified and accompanied by a further increase in IGF2 mRNA levels 35-fold
      higher than control values. Our results suggest that the combined effects of the
      H19/IGF2-imprinting center microdeletion and 11p15 chromosome duplication were
      necessary for manifestation of BWS.

PMID- 15743917
TI  - HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions
      caused by allopurinol.
AB  - Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a
      frequent cause of severe cutaneous adverse reactions (SCAR), which include the
      drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal
      necrolysis. The adverse events are unpredictable and carry significant morbidity
      and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a
      case-control association study. We enrolled 51 patients with allopurinol-SCAR and
      228 control individuals (135 allopurinol-tolerant subjects and 93 healthy
      subjects from the general population), and genotyped for 823 SNPs in genes
      related to drug metabolism and immune response. The initial screen revealed
      strong association between allopurinol-SCAR and SNPs in the MHC region, including
      BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB
      (MHC class I polypeptide-related sequence B) (P < 10(-7)). We then determined the
      alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all
      (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant
      patients [odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P
      value = 4.7 x 10(-24)] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23
      6665.26); corrected P value = 8.1 x 10(-18)]. HLA alleles A*3303, Cw*0302, and
      DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with
      HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated
      with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is
      an important genetic risk factor for this life-threatening condition.

PMID- 15743918
TI  - Borrelia burgdorferi sigma54 is required for mammalian infection and vector
      transmission but not for tick colonization.
AB  - Previous studies have shown that a sigma54-sigma(S) cascade regulates the
      expression of a few key lipoproteins in Borrelia burgdorferi, the agent of Lyme
      disease. Here, we demonstrate that these sigma factors, both together and
      independently, regulate a much more extensive number of genes and cellular
      processes. Microarray analyses of sigma54 and sigma(S) mutant strains identified
      305 genes regulated by sigma54 and 145 regulated by sigma(S), whereas the sigma54
      sigma(S) regulatory cascade appears to control 48 genes in B. burgdorferi. In
      silico analyses revealed that nearly 80% of genes with altered expression in the
      sigma54 mutant were linked to potential sigma54-dependent promoters. Many sigma54
      regulated genes are expressed in vivo, and through genetic complementation of the
      mutant, we demonstrated that sigma54 was required by B. burgdorferi to infect
      mammals. Surprisingly, sigma54 mutants were able to infect Ixodes scapularis
      ticks and be maintained for at least 24 wk after infection, suggesting the
      sigma54-sigma(S) regulatory network was not involved in long-term survival in
      ticks. However, sigma54 mutants did not enter the salivary glands during tick
      feeding, indicating that sigma54-regulated genes were involved in the
      transmission process.

PMID- 15743919
TI  - Endocrinological properties of two novel nonsteroidal progesterone receptor
      modulators, CP8816 and CP8863.
AB  - We have isolated PF1092A, B, and C, novel nonsteroidal progesterone ligands with
      preferential affinity for the progesterone receptor, from fermentation broth of a
      fungus [Tabata Y, Miike N, Hatsu M, Kurata Y, Yaguchi T, Someya A, Miyadoh S,
      Hoshiko S, Tsuruoka T, and Omoto S (1997) J Antibiot 50:304-308; Tabata Y, Hatsu
      M, Kurata Y, Miyajima K, Tani M, Sasaki T, Kodama Y, Tsuruoka T, and Omoto S
      (1997) J Antibiot 50:309-313]. The original skeleton of PF1092,
      tetrahydronaphthofuranone, was modified synthetically to produce a new skeleton,
      tetrahydrobenzindrone, and in the present study, biological activities of two
      derivatives, CP8816 [(4aR,5R,6R,7R)-6-(N,N-dimethylaminocarbonyl)oxy-7-methoxy
      4a,5,6,7-tetrahydro-1,3,4a,5-tetramethylbenz[f]indol-2(4H)-one] and CP8863
      [(4aR,5R,6R,7R)-7-hydroxy-6-(N-methylcarbamoyl)oxy-4a,5,6,7-tetrahydro-1,3,4a,5
      tetramethylbenz[f]indol-2(4H)-one], were investigated. Both CP8816 and CP8863
      demonstrated selective binding to progesterone receptor and partial agonistic
      activity in a progesterone-dependent endogenous alkaline phosphatase expression
      assay. In the Clauberg-McPhail test, progestational activity of CP8816 (0.1 mg/kg
      s.c. or 10 mg/kg p.o.) was comparable to that of progesterone (0.15 mg/kg s.c.),
      and oral administration of CP8863 at more than 1.0 mg/kg also exerted similar
      effects. Anti-estrogenic (antiuterotropic) activity was confirmed on daily oral
      application of more than 0.1 mg/kg CP8863 for 3 days by inhibition of estrogen
      dependent uterine wet weight gain in ovariectomized rats. CP8816 also exerted
      antiuterotropic activity at doses of 10 mg/kg (s.c.) and 100 mg/kg (p.o.). These
      results indicate that our nonsteroidal progesterone ligands have affinity for the
      progesterone receptor with partial progestational activity in vitro and clear
      progestational effects in vivo. Thus, these progesterone receptor modulator
      profiles suggest that CP8863 and CP8816 are good candidate compounds for
      treatment of hormone-dependent gynecological disorders.

PMID- 15743920
TI  - Characterization of the T-cell response in a patient with phenindione
      hypersensitivity.
AB  - The oral anticoagulant phenindione [2-phenyl-1H-indene-1,3(2H)-dione] is
      associated with hypersensitivity reactions in 1.5 to 3% of patients, the
      pathogenesis of which is unclear. We describe a patient who developed a severe
      hypersensitivity reaction that involved both the skin and lungs. A lymphocyte
      transformation test showed proliferation of T-cells from the hypersensitive
      patient, but not from four controls on exposure to phenindione in vitro. Drug
      specific T-cell clones were generated and characterized in terms of their
      phenotype, functionality, and mechanism of antigen presentation. Forty-three
      human leukocyte antigen class II restricted CD4(+) alphabeta T-cell clones were
      identified. T-cell activation resulted in the secretion of interferon-gamma and
      interleukin-5. Five of seven clones proliferated with phenindione alone, whereas
      two clones also proliferated with 2-phenylindene. Certain T-cell clones were also
      stimulated by R- and S-warfarin; computer modeling revealed that warfarin can
      adopt a phenindione-like structure. Phenindione was presented to T-cells via two
      pathways: first, bound directly to major histocompatibility complex and second,
      bound to a processed peptide. Our data show that CD4(+) T-cells are involved in
      the pathophysiology of phenindione hypersensitivity. There may be cross
      sensitivity with warfarin in some phenindione hypersensitive patients.

PMID- 15743921
TI  - Functional selectivity of melanocortin 4 receptor peptide and nonpeptide
      agonists: evidence for ligand-specific conformational states.
AB  - Agonists of the melanocortin 4 (MC4) receptor have potential pharmaceutical
      benefit in the treatment of obesity and sexual dysfunction. In this study, we
      have compared the ability of a number of peptide and nonpeptide agonists to
      activate a FLAG-tagged human MC4 (FMC4) receptor, as measured by both cAMP
      accumulation and calcium mobilization using a fluorometric imaging plate reader
      (FLIPR). In addition, we have analyzed the ability of these agonists to cause
      receptor internalization, as measured by fluorescence-activated cell sorting
      analysis. The endogenous agonist alpha-melanocortin-stimulating hormone (alpha
      MSH) increased cAMP accumulation, calcium mobilization, and receptor
      internalization in a dose-dependent manner in human embryonic kidney 293 cells
      expressing the FMC4 receptor. The activity of the other agonists varied
      considerably in these assays, and overall, the potency and intrinsic activity of
      the agonists in the cAMP accumulation assays did not correlate with their potency
      or intrinsic activity in either the FLIPR or receptor internalization assays.
      Agonists could be clearly separated into two functional classes based on their
      structure. Peptide agonists beta-MSH, des-acetyl-alpha-MSH, and [Nle(4), D
      Phe(7)]-alpha-melanocortin-stimulating hormone exhibited 80 to 112% of the
      maximal alpha-MSH response in cAMP accumulation and 62 to 96% in FLIPR assays and
      were able to cause 75 to 118% of receptor internalization induced by alpha-MSH.
      Conversely, although the nonpeptide agonists exhibited 73 to 149% of the alpha
      MSH response in the cAMP accumulation assays, they were significantly impaired in
      the FLIPR (7-40%) and receptor internalization (-5-38%) assays. These findings
      demonstrate an important difference in activation and internalization of the MC4
      receptor by nonpeptide versus peptide agonists and provides evidence of agonist
      specific conformational states.

PMID- 15743922
TI  - Acetazolamide, a carbonic anhydrase inhibitor, reverses inflammation-induced
      thermal hyperalgesia in rats.
AB  - Inflammatory pain is linked to reduction in tissue pH. Tissue proton generation
      is mainly mediated by carbonic anhydrases (CAs). We therefore hypothesized that
      inhibition of CAs with acetazolamide (ACTZ) increases the tissue pH and reverses
      inflammation-induced pain. CAs are also present in the central nervous system and
      control anion concentrations. Furthermore, ACTZ has direct effects on ion
      channels involved in nociception. In the current study, responses to heat and
      mechanical stimuli (von Frey filaments) of the paw were assessed before and after
      carrageenan-induced muscle inflammation and after treatment with ACTZ in rats.
      ACTZ was administered systemically, locally, or intrathecally 24 h after the
      induction of inflammation. In separate studies, pH was measured in the inflamed
      and noninflamed muscles and after administration of ACTZ. Carrageenan injection
      to the gastrocnemius muscle produced heat hyperalgesia and mechanical allodynia
      of the paw. Systemic ACTZ reversed the heat hyperalgesia but not mechanical
      allodynia. Similarly, injections of ACTZ into the inflamed muscle or
      intrathecally reversed the heat hyperalgesia but not mechanical allodynia.
      Surprisingly, the pH in the inflamed muscle was not reduced compared with
      noninflamed muscle. Thus, the current data do not support our hypothesis that
      ACTZ reduces inflammatory hyperalgesia by raising the reduced pH in muscle.
      Although the possibility of pH changes and the role of CAs in the
      microenvironment cannot be ruled out, the mechanism of ACTZ-induced
      antihyperalgesia is not clear from this study. It is possible that the inhibition
      of ion channels and/or the inhibition of spinally located CAs contribute to the
      observed antihyperalgesia.

PMID- 15743923
TI  - Dose-related distribution of codeine, cocaine, and metabolites into human hair
      following controlled oral codeine and subcutaneous cocaine administration.
AB  - Hair testing for the determination of drug exposure has many useful applications.
      Drug incorporated into hair can be found for extended periods following drug
      exposure. There are few controlled drug administration studies investigating drug
      distribution into human hair. Ten volunteers participated in a 10-week controlled
      cocaine and codeine administration study while residing in the secure research
      ward. Weekly hair samples were collected by electric razor. During the low-dose
      week (week 4), volunteers received 75 mg/70 kg cocaine subcutaneously and 60
      mg/70 kg codeine orally on alternating days, a total of three doses for each
      drug. Similarly, during week 7, volunteers received three doses 150 mg/70 kg
      cocaine and 120 mg/70 kg codeine. Maximum hair concentrations (C(max)) were found
      1 to 3 weeks after low and high doses. Dose-related C(max) values of cocaine,
      benzoylecgonine, ecgonine methyl ester, norcocaine, cocaethylene, and codeine
      were found following low and high doses. Hair analysis was performed using liquid
      chromatography tandem mass spectrometry. A positive linear relationship was found
      between total melanin content of hair and C(max) of codeine, cocaine, and
      metabolites following high dosing. This study demonstrated dose-related
      concentrations of cocaine and metabolites in human hair following controlled
      cocaine administration. These data are the first demonstrating melanin-related
      incorporation of cocaine and metabolites into human hair following controlled
      cocaine administration.

PMID- 15743925
TI  - Infection-induced kinin B1 receptors in human pulmonary fibroblasts: role of
      intact pathogens and p38 mitogen-activated protein kinase-dependent signaling.
AB  - Kinin B(1) receptors (B(1)R) are involved in many pathophysiological processes,
      and its expression is up-regulated in inflammatory pulmonary disease. Although
      bacteria can generate kinin peptides, the molecular signaling mechanisms
      regulating B(1)R during infection by intact pathogens is unknown. The serious
      opportunistic clinical isolate Burkholderia cenocepacia (B. cen.) belongs to the
      important B. cepacia complex (Bcc) of gram-negative pathogens that rapidly causes
      fatal pulmonary disease in hospitalized and immunocompromised patients and those
      with cystic fibrosis. We demonstrate here that B. cen. infection induced a rapid
      increase in B(1)R mRNA (1 h) proceeded by an increase in B(1)R protein expression
      (2 h), without affecting B(2) receptor expression in human pulmonary fibroblasts.
      The B(1)R response was dose-dependent and maximal by 6 to 8 h (3- to 4-fold
      increase), however, brief B. cen. infection could sustain B(1)R up-regulation. In
      contrast, nonclinical Bcc phytopathogens were much less B(1)R inducive. The
      protein synthesis inhibitor cycloheximide and transcriptional inhibitor
      actinomycin D abrogated the B(1) response to B. cen. indicating de novo B(1)R
      synthesis. B. cen. activated p38 mitogen-activated protein kinase (MAPK), and
      blocking p38 MAPK with the specific inhibitor 4-(4-fluorophenyl)-2-(4
      methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB 203580) dramatically reduced
      B. cen.-induced B(1)R. Furthermore, B. cen. regulation of B(1)R was diminished by
      the anti-inflammatory glucocorticoid dexamethasone. In conclusion, this study is
      the first demonstration that infection with intact pulmonary pathogens like B.
      cen. positively modulates the selective expression of B(1)R. Thus, providing
      evidence that B(1)R regulation may be an important and novel mechanism in the
      inflammatory cascade in response to chronic pulmonary infection and disease.

PMID- 15743924
TI  - Quantitative measurement of changes in amyloid-beta(40) in the rat brain and
      cerebrospinal fluid following treatment with the gamma-secretase inhibitor LY
      411575 [N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6
      oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide].
AB  - The efficacy of gamma-secretase inhibitors in vivo has, to date, been generally
      assessed in transgenic mouse models expressing increased levels of amyloid-beta
      (Abeta) peptide thereby allowing the detection of changes in Abeta production.
      However, it is not clear whether the in vivo potency of gamma-secretase
      inhibitors is independent of the level of amyloid precursor protein expression.
      In other words, does a gamma-secretase inhibitor have the same effect in
      nontransgenic physiological animals versus transgenic overexpressing animals? In
      the present study, an immunoassay has been developed which can detect Abeta(40)
      in the rat brain, where concentrations are much lower than those seen in
      transgenic mice such as Tg2576 (c. 0.7 and 25 nM, respectively) and in
      cerebrospinal fluid (CSF, c. 0.3 nM). Using this immunoassay, the effects of the
      gamma-secretase inhibitor LY-411575 [N(2)-[(2S)-2-(3,5-difluorophenyl)-2
      hydroxyethanoyl]-N(1)-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7
      yl]-L-alaninamide] were assessed and robust dose-dependent reductions in rat
      brain and CSF Abeta(40) levels were observed with ID(50) values of 1.3 mg/kg for
      both brain and CSF. These values were comparable with those calculated for LY
      411575 in transgenic mice. Time course experiments using LY-411575 demonstrated
      comparable temporal reductions in rat brain and CSF Abeta(40), further suggesting
      these two pools of Abeta are related. Accordingly, when all the data for the dose
      response curve and time course were correlated, a strong association was observed
      between the brain and CSF Abeta(40) levels. These data demonstrate the utility of
      the rat as a novel approach for assessing the effects of gamma-secretase
      inhibitors on central nervous system Abeta(40) levels in vivo.

PMID- 15743926
TI  - Transcriptional and translational regulation of glial activation by morphine in a
      rodent model of neuropathic pain.
AB  - Glial cells function in maintenance of homeostasis as well as in pathophysiology.
      In this study, we determined the time course of spinal glial cell activation
      during the development of morphine analgesic tolerance in an L5 spinal nerve
      transection rodent model of neuropathic pain. We also sought to assess whether
      the method of morphine administration affected neuroimmune activation at the
      levels of transcription and translation. Rats received L5 spinal nerve
      transection or no surgery on day 0. On day 6 post-transection, osmotic minipumps
      were implanted to deliver saline or morphine s.c. (1 or 10 mg/kg) or i.t. (5 or
      20 nmol/h). Mechanical allodynia developed immediately after spinal nerve
      transection; this hypersensitivity was reversed with both low- and high-dose
      morphine by either route. Tolerance to antiallodynia developed after 3 days of
      i.t. morphine and after 6 days of s.c. morphine, indicating hastened tolerance
      following i.t. delivery. Analysis of mRNA revealed that s.c. morphine treatment
      did not lead to increases in glial activation markers. In contrast, i.t. morphine
      caused a biphasic alteration in glial fibrillary acidic protein (GFAP) and
      integrin alpha M mRNA. Protein levels for GFAP were elevated after s.c. and i.t.
      administration of morphine; however, induction was further enhanced in the latter
      group. Here, we show for the first time that there is differential recruitment of
      transcriptional and translational mechanisms of glial activation by systemic and
      i.t. morphine. Furthermore, we suggest that enhanced neuroimmune activation after
      i.t. dosing contributes to the hastened development of analgesic tolerance seen
      in these animals.

PMID- 15743928
TI  - Use of a physiologically based pharmacokinetic model to study the time to reach
      brain equilibrium: an experimental analysis of the role of blood-brain barrier
      permeability, plasma protein binding, and brain tissue binding.
AB  - This study was designed 1) to examine the effects of blood-brain barrier (BBB)
      permeability [quantified as permeability-surface area product (PS)], unbound
      fraction in plasma (f(u,plasma)), and brain tissue (f(u,brain)) on the time to
      reach equilibrium between brain and plasma and 2) to investigate the drug
      discovery strategies to design and select compounds that can rapidly penetrate
      the BBB and distribute to the site of action. The pharmacokinetics of seven model
      compounds: caffeine, CP-141938 [methoxy-3-[(2-phenyl-piperadinyl-3-amino)-methyl]
      phenyl-N-methyl-methane-sulfonamide], fluoxetine, NFPS [N[3-(4'-fluorophenyl)-3
      (4'-phenylphenoxy)propyl]sarcosine], propranolol, theobromine, and theophylline
      in rat brain and plasma after subcutaneous administration were studied. The in
      vivo log PS and log f(u,brain) calculated using a physiologically based
      pharmacokinetic model correlates with in situ log PS (R(2) = 0.83) and in vitro
      log f(u,brain) (R(2) = 0.69), where the in situ PS and in vitro f(u,brain) was
      determined using in situ brain perfusion and equilibrium dialysis using brain
      homogenate, respectively. The time to achieve brain equilibrium can be
      quantitated with a proposed parameter, intrinsic brain equilibrium half-life
      [t(1/2eq,in) = V(b)ln2/(PS . f(u,brain))], where V(b) is the physiological volume
      of brain. The in vivo log t(1/2eq,in) does not correlate with in situ log PS
      (R(2) < 0.01) but correlates inversely with log(PS . f(u,brain)) (R(2) = 0.85).
      The present study demonstrates that rapid brain equilibration requires a
      combination of high BBB permeability and low brain tissue binding. A high BBB
      permeability alone cannot guarantee a rapid equilibration. The strategy to select
      compounds with rapid brain equilibration in drug discovery should identify
      compounds with high BBB permeability and low nonspecific binding in brain tissue.

PMID- 15743927
TI  - 5-Hydroxytryptamine 1A receptors in the paraventricular nucleus of the
      hypothalamus mediate oxytocin and adrenocorticotropin hormone release and some
      behavioral components of the serotonin syndrome.
AB  - Neuroendocrine responses to administration of serotonin releasing agents or 5
      hydroxytryptamine (5-HT) 1A receptor agonists have been used as an index of
      serotonin receptor function in patients with depression and other mood disorders.
      However, the receptor population that mediates these responses has not been
      clearly identified. We tested the hypothesis that 5-HT1A receptors in the
      paraventricular nucleus of the hypothalamus (PVN) mediate the release of
      adrenocorticotropin hormone (ACTH) and oxytocin after administration of a
      selective 5-HT1A agonist in conscious rats. Low-dose infusion (1 nmol/100
      nl/side) of the selective 5-HT1A antagonist, WAY100635 (WAY; [O-methyl-3H]-N-(2
      (4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-N-(2
      pyridinyl)cyclohexanecarboxamidetrihydrochloride), into the PVN blocked the rise
      in ACTH and oxytocin stimulated by low-dose (30 nmol/kg) i.v. administration of
      the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 274 +/- 53
      versus 70 +/- 20 pg/ml, P < 0.01 for ACTH and 10.7 +/- 3.4 versus 4.6 +/- 0.7
      pg/ml, P < 0.05 for oxytocin after saline or WAY pretreatment, respectively). WAY
      did not influence the bradycardic effect of 8-OH-DPAT (-56 +/- 7 versus -54 +/- 6
      beats per minute after saline or WAY). 8-OH-DPAT treatment also elicited
      locomotor activation followed by hind limb abduction and flat body posture.
      Surprisingly, WAY attenuated some aspects of locomotor activation and reduced the
      duration of hind limb abduction elicited by the agonist (5.1 +/- 0.9 versus 0.3
      +/- 0.3 min for saline- or WAY-treated rats). These data indicate that 5-HT1A
      receptor stimulation in the PVN mediates the characteristic neuroendocrine
      response to serotonin agonist challenge. Moreover, they provide the first
      evidence that aspects of the behavioral serotonin syndrome are mediated by
      forebrain hypothalamic receptors.

PMID- 15743929
TI  - Place conditioning and locomotor effects of N-substituted, 4',4''
      difluorobenztropine analogs in rats.
AB  - Previous studies demonstrated that analogs of benztropine [3alpha-(diphenyl
      methoxy)tropane (BZT)] bind to the dopamine (DA) transporter with high affinity,
      inhibit DA uptake, but do not maintain rates of responding in self-administration
      procedures comparable with those maintained by cocaine. Some BZT analogs have an
      onset of action that is slower than that for cocaine that may contribute to this
      decreased effectiveness. In addition, some BZT analogs have affinity for
      muscarinic-M1 receptors that may interfere with reinforcing effects. The present
      study assessed effects of BZT analogs in place-conditioning procedures designed
      to accommodate variations in onset of effect. BZT analogs with variations in
      relative affinities for the DA transporter over M1 receptors from equal [AHN 1
      055 (3alpha-[bis(4'-fluorophenyl)methoxy]-tropane)] to 16-fold [JHW 007 (N-(n
      butyl)-3alpha-[bis(4'-fluorophenyl)methoxy]-tropane)] were compared with cocaine
      and the muscarinic antagonist, atropine. Cocaine (10-20 mg/kg) but not atropine
      (1.0-5.6 mg/kg) produced dose-related place conditioning. The N-methyl
      substituted BZT analog, AHN 1-055, was without significant effects at doses that
      ranged from 0.3 to 3.0 mg/kg and when administered up to 90 min before
      conditioning trials. In contrast, effects of AHN 2-005 (N-allyl-3alpha-[bis(4'
      fluorophenyl)methoxy]-tropane; 0.1-10.0 mg/kg) were significant, and those of JHW
      007 approached significance when administered 45 min but not immediately or 90
      min before trials. Atropine blocked the effect of AHN 2-005 and approached
      significant antagonism of cocaine. The present study further supports and extends
      previous results showing minimal preclinical indications of abuse liability of
      BZT analogs and suggests that these differences from cocaine are not entirely
      accounted for by a slower onset of action or muscarinic M1 receptor affinity.

PMID- 15743930
TI  - Identification of subunit- and antagonist-specific amino acid residues in the N
      Methyl-D-aspartate receptor glutamate-binding pocket.
AB  - The resolved X-ray crystal structures of the glutamate-binding domain (S1/S2
      domains) of the GluR2 and NR1 glutamate receptor subunits were used to model the
      homologous regions of the N-methyl-D-aspartate (NMDA) receptor's NR2 subunits. To
      test the predictive value of these models, all four stereoisomers of the
      antagonist 1-(phenanthren-2-carbonyl) piperazine-2,3-dicarboxylic acid (PPDA)
      were docked into the NR2B glutamate-binding site model. This analysis suggested
      an affinity order for the PPDA isomers of d-cis > L-cis > L-trans = D-trans and
      predicted that the 2-position carboxylate group of the cis-PPDA isomers, but not
      of the trans-PPDA isomers, may be interacting with histidine 486 in NR2B.
      Consistent with these predictions, cis-PPDA displays a 35-fold higher affinity
      for NR2B-containing NMDA receptors than trans-PPDA. In addition, mutating NR2B's
      H486 to phenylalanine decreased cis-PPDA affinity 8-fold but had no effect on
      trans-PPDA affinity. In contrast, the NR2B H486F mutation increased the affinity
      of the typical antagonists CGS-19755 [(2R*,4S*)-4-phosphonomethyl-2-piperidine
      carboxylic acid] and 4-(3-phosphonopropyl) piperidine-2-carboxylic acid. In the
      NR1-based NR2 models, there were only four subunit-specific amino acid residues
      exposed to the ligand-binding pocket (and six in the GluR2-based models). These
      residues are located at the edge of the binding pocket, suggesting that large
      antagonists may be necessary for subtype specificity. Of these residues,
      mutational analysis and modeling suggest that A414, R712, and G713 (NR2B
      numbering) may be especially useful for developing NR2C- and NR2D-selective NMDA
      receptor antagonists and that residues A414 and T428 may determine subunit
      variations in agonist affinity.

PMID- 15743931
TI  - Opposing roles of endothelial and smooth muscle phosphatidylinositol 3-kinase in
      vasoconstriction: effects of rho-kinase and hypertension.
AB  - Phosphatidylinositol 3-kinase (PI3K) can activate endothelial nitric oxide
      synthase (eNOS), leading to production of the vasodilator NO. In contrast,
      vascular smooth muscle (VSM) PI3K may partially mediate vascular contraction,
      particularly during hypertension. We tested whether endothelial and VSM PI3K may
      have opposing functional roles in regulating vascular contraction. Secondly, we
      tested whether the procontractile protein rho-kinase can suppress endothelial
      PI3K/eNOS activity in intact arteries, thus contributing to vasoconstriction by G
      protein-coupled receptor (GPCR) agonists. We studied contractile responses to the
      GPCR agonist phenylephrine, and the receptor-independent vasoconstrictor KCl, in
      aortic rings from Sprague-Dawley rats. In endothelium-intact rings, the PI3K
      inhibitor wortmannin (0.1 microM) markedly augmented responses to phenylephrine
      (P < 0.05) by approximately 50% but not to KCl. However, in endothelium-denuded
      or N(G)-nitro-L-arginine methyl ester (L-NAME) (100 microM)-treated rings,
      wortmannin reduced responses to phenylephrine and KCl (P < 0.05). Furthermore,
      the rhokinase inhibitor Y-27632 (R-[+]-trans-N-[4-pyridyl]-4-[1-aminoethyl]
      cycloheaxanecarboxamide; 1 microM) abolished responses to phenylephrine, and this
      effect was partially reversed by wortmannin or L-NAME. The ability of wortmannin
      to oppose the effect of rho-kinase inhibition on contractions to phenylephrine
      was L-NAME-sensitive. In aortas from angiotensin II-induced hypertensive rats,
      relaxation to acetylcholine (10 microM) was impaired (P < 0.05), and
      vasoconstriction by phenylephrine was markedly enhanced and not further augmented
      by wortmannin. These data suggest that endothelial PI3K-induced NO production can
      modulate GPCR agonist-induced vascular contraction and that this effect is
      impaired in hypertension in association with endothelial dysfunction. In
      addition, endothelial rho-kinase may act to suppress PI3K activity and, hence,
      attenuate NO-mediated relaxation and augment GPCR-dependent contraction.

PMID- 15743932
TI  - Pharmacokinetic analysis of the blood-brain barrier transport of 125I-amyloid
      beta protein 40 in wild-type and Alzheimer's disease transgenic mice (APP,PS1)
      and its implications for amyloid plaque formation.
AB  - Amyloid plaques are formed in the extracellular space of Alzheimer's disease (AD)
      brain due to the accumulation of amyloid beta (Abeta) proteins such as Abeta40.
      The relationship between Abeta40 pharmacokinetics and its accumulation within and
      clearance from the brain in both wild-type (WT) and AD transgenic mice (APP,PS1)
      was studied to understand the mechanism of amyloid plaque formation and the
      potential use of Abeta40 as a probe to target and detect amyloid plaques. In both
      WT and APP,PS1 mice, the (125)I-Abeta40 tracer exhibited biexponential
      disposition in plasma with very short first and second phase half-lives. The
      (125)I-Abeta40 was significantly metabolized in the liver kidney > spleen.
      Coadministration of exogenous Abeta40 inhibited the plasma clearance and the
      uptake of (125)I-Abeta40 at the blood-brain barrier (BBB) in WT animals but did
      not affect its elimination from the brain. The (125)I-Abeta40 was shown to be
      metabolized within and effluxed from the brain parenchyma. The rate of efflux
      from APP,PS1 brain slices was substantially lower compared with WT brain slices.
      Since the Abeta40 receptor at the BBB can be easily saturated, the blood-to-brain
      transport of Abeta40 is less likely to be a primary contributor to the amyloid
      plaque formation in APP,PS1 mice. The decreased elimination of Abeta40 from the
      brain is most likely responsible for the amyloid plaque formation in the brain of
      APP,PS1 mice. Furthermore, inadequate targeting of Abeta40 to amyloid plaques,
      despite its high BBB permeability, is due to the saturability of Abeta40
      transporter at the BBB and its metabolism and efflux from the brain.

PMID- 15743933
TI  - Vacuuming the periplasm.

PMID- 15743934
TI  - Effects of tryptophan starvation on levels of the trp RNA-binding attenuation
      protein (TRAP) and anti-TRAP regulatory protein and their influence on trp operon
      expression in Bacillus subtilis.
AB  - The anti-TRAP protein (AT), encoded by the rtpA gene of Bacillus subtilis, can
      bind to and inhibit the tryptophan-activated trp RNA-binding attenuation protein
      (TRAP). AT binding can prevent TRAP from promoting transcription termination in
      the leader region of the trp operon, thereby increasing trp operon expression. We
      show here that AT levels continue to increase as tryptophan starvation becomes
      more severe, whereas the TRAP level remains relatively constant and independent
      of tryptophan starvation. Assuming that the functional form of AT is a trimer, we
      estimate that the ratios of AT trimers per TRAP molecule are 0.39 when the cells
      are grown under mild tryptophan starvation conditions, 0.83 under more severe
      starvation conditions, and approximately 2.0 when AT is expressed maximally. As
      the AT level is increased, a corresponding increase is observed in the
      anthranilate synthase level. When AT is expressed maximally, the anthranilate
      synthase level is about 70% of the level observed in a strain lacking TRAP. In a
      nutritional shift experiment where excess phenylalanine and tyrosine could
      potentially starve cells of tryptophan, both the AT level and anthranilate
      synthase activity were observed to increase. Expression of the trp operon is
      clearly influenced by the level of AT.

PMID- 15743935
TI  - Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis
      mutants hypersusceptible to beta-lactam antibiotics.
AB  - Our laboratory previously constructed mutants of Mycobacterium tuberculosis and
      Mycobacterium smegmatis with deletions in the genes for their major beta
      lactamases, BlaC and BlaS, respectively, and showed that the mutants have
      increased susceptibilities to most beta-lactam antibiotics, particularly the
      penicillins. However, there is still a basal level of resistance in the mutants
      to certain penicillins, and the susceptibilities of the mutants to some
      cephalosporin-based beta-lactams are essentially the same as those of the wild
      types. We hypothesized that characterizing additional mutants (derived from beta
      lactamase deletion mutants) that are hypersusceptible to beta-lactam antibiotics
      might reveal novel genes involved with other mechanisms of beta-lactam
      resistance, peptidoglycan assembly, and cell envelope physiology. We report here
      the isolation and characterization of nine beta-lactam antibiotic
      hypersusceptible transposon mutants, two of which have insertions in genes known
      to be involved with peptidoglycan biosynthesis (ponA2 and dapB); the other seven
      mutants have insertions which affect novel genes. These genes can be classified
      into three groups: those involved with peptidoglycan biosynthesis, cell division,
      and other cell envelope processes. Two of the peptidoglycan-biosynthetic genes
      (ponA2 and pbpX) may encode beta-lactam antibiotic-resistant enzymes proposed to
      be involved with the synthesis of the unusual diaminopimelyl linkages within the
      mycobacterial peptidoglycan.

PMID- 15743936
TI  - Percolation of the phd repressor-operator interface.
AB  - Transcription of the P1 plasmid addiction operon, a prototypical toxin-antitoxin
      system, is negatively autoregulated by the products of the operon. The Phd
      repressor-antitoxin protein binds to 8-bp palindromic Phd-binding sites in the
      promoter region and thereby represses transcription. The toxin, Doc, mediates
      cooperative interactions between adjacent Phd-binding sites and thereby enhances
      repression. Here, we describe a homologous operon from Salmonella enterica
      serovar Typhimurium which has the same pattern of regulation but an altered
      repressor-operator specificity. This difference in specificity maps to the
      seventh amino acid of the repressor and to the symmetric first and eighth
      positions of the corresponding palindromic repressor-binding sites. Thus, the
      repressor-operator interface has coevolved so as to retain the interaction while
      altering the specificity. Within an alignment of homologous repressors, the
      seventh amino acid of the repressor is highly variable, indicating that
      evolutionary changes in repressor specificity may be common in this protein
      family. We suggest that the robust properties of the negative feedback loop, the
      fuzzy recognition in the operator-repressor interface, and the duplication and
      divergence of the repressor-binding sites have facilitated the speciation of this
      repressor-operator interface. These three features may allow the repressor
      operator system to percolate within a nearly neutral network of single-step
      mutations without the necessity of invoking simultaneous mutations, low-fitness
      intermediates, or other improbable or rate-limiting mechanisms.

PMID- 15743937
TI  - Helical disposition of proteins and lipopolysaccharide in the outer membrane of
      Escherichia coli.
AB  - In bacteria, several physiological processes once thought to be the products of
      uniformly dispersed reactions are now known to be highly asymmetric, with some
      exhibiting interesting geometric localizations. In particular, the cell envelope
      of Escherichia coli displays a form of subcellular differentiation in which
      peptidoglycan and outer membrane proteins at the cell poles remain stable for
      generations while material in the lateral walls is diluted by growth and
      turnover. To determine if material in the side walls was organized in any way, we
      labeled outer membrane proteins with succinimidyl ester-linked fluorescent dyes
      and then grew the stained cells in the absence of dye. Labeled proteins were not
      evenly dispersed in the envelope but instead appeared as helical ribbons that
      wrapped around the outside of the cell. By staining the O8 surface antigen of E.
      coli 2443 with a fluorescent derivative of concanavalin A, we observed a similar
      helical organization for the lipopolysaccharide (LPS) component of the outer
      membrane. Fluorescence recovery after photobleaching indicated that some of the
      outer membrane proteins remained freely diffusible in the side walls and could
      also diffuse into polar domains. On the other hand, the LPS O antigen was
      virtually immobile. Thus, the outer membrane of E. coli has a defined in vivo
      organization in which a subfraction of proteins and LPS are embedded in stable
      domains at the poles and along one or more helical ribbons that span the length
      of this gram-negative rod.

PMID- 15743938
TI  - Aminoglycosides are captured from both periplasm and cytoplasm by the AcrD
      multidrug efflux transporter of Escherichia coli.
AB  - To understand better the mechanisms of resistance-nodulation-division (RND)-type
      multidrug efflux pumps, we examined the Escherichia coli AcrD pump, whose typical
      substrates, aminoglycosides, are not expected to diffuse spontaneously across the
      lipid bilayer. The hexahistidine-tagged AcrD protein was purified and
      reconstituted into unilamellar proteoliposomes. Its activity was measured by the
      proton flux accompanying substrate transport. When the interior of the
      proteoliposomes was acidified, the addition of aminoglycosides to the external
      medium stimulated proton efflux and the intravesicular accumulation of
      radiolabeled gentamicin, suggesting that aminoglycosides can be captured and
      transported from the external medium in this system (corresponding to cytosol).
      This activity required the presence of AcrA within the proteoliposomes.
      Interestingly, the increase in proton efflux also occurred when aminoglycosides
      were present only in the intravesicular space. This result suggested that AcrD
      can also capture aminoglycosides from the periplasm to extrude them into the
      medium in intact cells, acting as a "periplasmic vacuum cleaner."

PMID- 15743939
TI  - SpoIIE regulates sporulation but does not directly affect solventogenesis in
      Clostridium acetobutylicum ATCC 824.
AB  - Using gene expression reporter vectors, we examined the activity of the spoIIE
      promoter in wild-type and spo0A-deleted strains of Clostridium acetobutylicum
      ATCC 824. In wild-type cells, the spoIIE promoter is active in a transient manner
      during late solventogenesis, but in strain SKO1, where the sporulation initiator
      spo0A is disrupted, no spoIIE promoter activity is detectable at any stage of
      growth. Strains 824(pMSpo) and 824(pASspo) were created to overexpress spoIIE and
      to decrease spoIIE expression via antisense RNA targeted against spoIIE,
      respectively. Some cultures of strains 824(pMSpo) degenerated during
      fermentations by losing the pSOL1 megaplasmid and hence did not produce the
      solvents ethanol, acetone, and butanol. The frequent degeneration event was shown
      to require an intact copy of spoIIE. Nondegenerate cultures of 824(pMSpo)
      exhibited normal growth and solvent production. Strain 824(pASspo) exhibited
      prolonged solventogenesis characterized by increased production of ethanol
      (225%), acetone (43%), and butanol (110%). Sporulation in strains harboring
      pASspo was significantly delayed, with sporulating cells exhibiting altered
      morphology. These results suggest that SpoIIE has no direct effect on the control
      of solventogenesis and that the changes in solvent production in spoIIE
      downregulated cells are mediated by effects on the cell during sporulation.

PMID- 15743940
TI  - Menaquinone-specific prenyl reductase from the hyperthermophilic archaeon
      Archaeoglobus fulgidus.
AB  - Four genes that encode the homologues of plant geranylgeranyl reductase were
      isolated from a hyperthermophilic archaeon Archaeoglobus fulgidus, which produces
      menaquinone with a fully saturated heptaprenyl side chain, menaquinone-7(14H).
      The recombinant expression of one of the homologues in Escherichia coli led to a
      distinct change in the quinone profile of the host cells, although the homologue
      is the most distantly related to the geranylgeranyl reductase. The new compounds
      found in the profile had successively longer elution times than those of ordinary
      quinones from E. coli, i.e., menaquinone-8 and ubiquinone-8, in high-performance
      liquid chromatography on a reversed-phase column. Structural analyses of the new
      compounds by electron impact-mass spectrometry indicated that their molecular
      masses progressively increase relative to the ordinary quinones at a rate of 2 U
      but that they still contain quinone head structures, strongly suggesting that the
      compounds are quinones with partially saturated prenyl side chains. In vitro
      assays with dithionite as the reducing agent showed that the prenyl reductase is
      highly specific for menaquinone-7, rather than ubiquinone-8 and prenyl
      diphosphates. This novel enzyme noncovalently binds flavin adenine dinucleotide,
      similar to geranylgeranyl reductase, but was not able to utilize NAD(P)H as the
      electron donor, unlike the plant homologue.

PMID- 15743941
TI  - Bactericidal activity of colicin V is mediated by an inner membrane protein,
      SdaC, of Escherichia coli.
AB  - Colicin V (ColV) is a peptide antibiotic that kills sensitive cells by disrupting
      their membrane potential once it gains access to the inner membrane from the
      periplasmic face. Recently, we constructed a translocation suicide probe, RR
      ColV, that is translocated into the periplasm via the TAT pathway and thus kills
      the host cells. In this study, we obtained an RR-ColV-resistant mutant by using
      random Tn10 transposition mutagenesis. Sequencing analysis revealed that the
      mutant carried a Tn10 insertion in the sdaC (also called dcrA) gene, which is
      involved in serine uptake and is required for C1 phage adsorption. ColV activity
      was detected both in the cytoplasm and in the periplasm of this mutant,
      indicating that RR-ColV was translocated into the periplasm but failed to
      interact with the inner membrane. The sdaC::Tn10 mutant was resistant only to
      ColV and remained sensitive to colicins Ia, E3, and A. Most importantly, the
      sdaC::Tn10 mutant was killed when ColV was anchored to the periplasmic face of
      the inner membrane by fusion to EtpM, a type II integral membrane protein. Taken
      together, these results suggest that the SdaC/DcrA protein serves as a specific
      inner membrane receptor for ColV.

PMID- 15743942
TI  - Modulation of mRNA stability participates in stationary-phase-specific expression
      of ribosome modulation factor.
AB  - The expression of ribosome modulation factor (RMF) is induced during stationary
      phase in Escherichia coli. RMF participates in the dimerization of 70S ribosomes
      to form the 100S ribosome, which is the translationally inactive form of the
      ribosome. To elucidate the involvement of the control of mRNA stability in growth
      phase-specific rmf expression, we investigated rmf mRNA stability in stationary
      phase cells and cells inoculated into fresh medium. The rmf mRNA was found to
      have an extremely long half-life during stationary phase, whereas destabilization
      of this mRNA took place after the culture was inoculated into fresh medium. RMF
      and 100S ribosomes disappeared from cells 1 min after inoculation. In addition to
      control by ppGpp-dependent transcription, these results indicate that the
      modulation of rmf mRNA stability is also involved in the regulation of growth
      phase-specific rmf expression. Unexpectedly, the postinoculation degradation of
      rmf mRNA was suppressed by the addition of rifampin, suggesting that de novo RNA
      synthesis is necessary for degradation. This degradation was also suppressed in
      both a poly(A) polymerase-deficient and an rne-131 mutant strain. We cloned and
      sequenced the 3'-proximal regions of rmf mRNAs and found that most of these 3'
      ends terminated at the rho-independent terminator with the addition of a one- to
      five-A oligo(A) tail in either stationary-phase or inoculated cells. No
      difference was observed in the length of the poly(A) tail between stationary
      phase and inoculated cells. These results suggest that a certain postinoculation
      specific regulatory factor participates in the destabilization of rmf mRNA and is
      dependent on polyadenylation.

PMID- 15743944
TI  - GIL16, a new gram-positive tectiviral phage related to the Bacillus thuringiensis
      GIL01 and the Bacillus cereus pBClin15 elements.
AB  - One of the most notable characteristics of Tectiviridae resides in their double
      layer coats: the double-stranded DNA is located within a flexible lipoprotein
      vesicle covered by a rigid protein capsid. Despite their apparent rarity,
      tectiviruses have an extremely wide distribution compared to other phage groups.
      Members of this family have been found to infect gram-negative (PRD1 and
      relatives) as well as gram-positive (Bam35, GIL01, AP50, and phiNS11) hosts.
      Several reports have shown that tectiviruses infecting gram-negative bacteria are
      closely related, whereas no information is currently available on the genetic
      relationship among those infecting gram-positive bacteria. The present study
      reports the sequence of GIL16, a new isolate originating from Bacillus
      thuringiensis, and a genetic comparison of this isolate with the tectiviral
      bacteriophages Bam35 and GIL01, which originated from B. thuringiensis serovars
      Alesti and Israelensis, respectively. In contrast to PRD1 and its relatives,
      these are temperate bacteriophages existing as autonomous linear prophages within
      the host cell. Mutations in a particular motif in both the GIL01 and GIL16 phages
      are also shown to correlate with a switch to the lytic cycle. Interestingly, both
      bacterial viruses displayed narrow, yet slightly different, host spectrums. We
      also explore the hypothesis that pBClin15, a linear plasmid hosted by the
      Bacillus cereus reference strain ATCC 14579, is also a prophage. Sequencing of
      its inverted repeats at both extremities and a comparison with GIL01 and GIL16
      emphasize its relationship to the Tectiviridae.

PMID- 15743943
TI  - Function and expression of an N-acetylneuraminic acid-inducible outer membrane
      channel in Escherichia coli.
AB  - The Escherichia coli yjhA (renamed nanC) gene encodes a protein of the KdgM
      family of outer membrane-specific channels. It is transcribed divergently from
      fimB, a gene involved in the site-specific inversion of the region controlling
      transcription of the fimbrial structural genes but is separated from it by one of
      the largest intergenic regions in E. coli. We show that nanC expression is
      induced by N-acetylneuraminic acid and modulated by N-acetylglucosamine. This
      regulation occurs via the NanR and NagC regulators, which also control fimB
      expression. nanC expression is also activated by the regulators cyclic AMP
      catabolite activator protein, OmpR, and CpxR. When the NanC protein was
      reconstituted into liposomes, it formed channels with a conductance of 450 pS at
      positive potential and 300 to 400 pS at negative potential in 800 mM KCl. The
      channels had a weak anionic selectivity. In an ompR background, where the general
      porins OmpF and OmpC are absent, NanC is required for growth of E. coli on N
      acetylneuraminic acid as the sole carbon source. All these results suggest that
      NanC is an N-acetylneuraminic acid outer membrane channel protein.

PMID- 15743945
TI  - In vivo evidence for a recA-independent recombination process in Escherichia coli
      that permits completion of replication of DNA containing UV damage in both
      strands.
AB  - We have investigated recombination mechanisms promoting the completion of
      replication in the face of unrepaired DNA damage by transforming an isogenic set
      of uvrA6 excision-defective Escherichia coli strains with pUC-based plasmids in
      which each strand carried, at staggered positions, a single thymine-thymine
      pyrimidine (6-4) pyrimidinone lesion. The distance between the lesions was 28 or
      8 bp in one orientation relative to the unidirectional ColE1 origin of
      replication or, in the other orientation, 30 or 10 bp. C-C mismatches placed
      opposite each of the T-T photoproducts permit unambiguous detection of the three
      events that can lead to the completion of replication: sister-strand
      recombination, translesion replication (TR) on the leading strand, and TR on the
      lagging strand. We find that E. coli possesses a largely constitutive, recA
      independent sister-strand recombination mechanism that allows 9% or more of these
      severely compromised plasmids to be fully replicated. In one orientation, such
      recombination depends partly on recG and priA but not on ruvA, ruvB, ruvC, or
      mutS and is largely independent of recF. In the other orientation, recombination
      is dependent on none of the genes. The strains used did not contain the cryptic
      phage encoding recET, which encodes enzymes that promote interplasmid
      recombination. The nature of the recA-independent recombination mechanism is not
      known but could perhaps result from a template-strand-switching, or copy choice,
      process.

PMID- 15743946
TI  - HetR-dependent and -independent expression of heterocyst-related genes in an
      Anabaena strain overproducing the NtcA transcription factor.
AB  - Heterocyst development in the cyanobacterium Anabaena sp. strain PCC 7120 depends
      on both the global nitrogen control transcription factor NtcA and the cell
      differentiation regulatory protein HetR, with expression of ntcA and hetR being
      dependent on each other. In this study we constructed strains that constitutively
      express the ntcA gene leading to high levels of NtcA protein irrespective of the
      nitrogen source, and we analyzed the effects of such NtcA levels on heterocyst
      differentiation. In the NtcA-overproducing strain, heterocyst differentiation,
      induction of NtcA-dependent heterocyst development genes or operons such as
      devBCA or the cox2 operon, and NtcA-dependent excision of the 11-kb nifD
      intervening element only took place under nitrogen deficiency. Although
      functional heterocysts were produced in response to nitrogen step-down, the NtcA
      overproducing strain could not grow diazotrophically. Overexpression of ntcA in a
      hetR background promoted expression of devBCA in response to ammonium withdrawal
      and excision of the 11-kb element even in the presence of combined nitrogen. Our
      results show that some NtcA-dependent heterocyst-related genes can be expressed
      independently of HetR.

PMID- 15743947
TI  - Functional domains of NosR, a novel transmembrane iron-sulfur flavoprotein
      necessary for nitrous oxide respiration.
AB  - Bacterial nitrous oxide (N2O) respiration depends on the polytopic membrane
      protein NosR for the expression of N2O reductase from the nosZ gene. We
      constructed His-tagged NosR and purified it from detergent-solubilized membranes
      of Pseudomonas stutzeri ATCC 14405. NosR is an iron-sulfur flavoprotein with
      redox centers positioned at opposite sides of the cytoplasmic membrane. The
      flavin cofactor is presumably bound covalently to an invariant threonine residue
      of the periplasmic domain. NosR also features conserved CX3CP motifs, located C
      terminally of the transmembrane helices TM4 and TM6. We genetically manipulated
      nosR with respect to these different domains and putative functional centers and
      expressed recombinant derivatives in a nosR null mutant, MK418nosR::Tn5. NosR's
      function was studied by its effects on N2O respiration, NosZ synthesis, and the
      properties of purified NosZ proteins. Although all recombinant NosR proteins
      allowed the synthesis of NosZ, a loss of N2O respiration was observed upon
      deletion of most of the periplasmic domain or of the C-terminal parts beyond TM2
      or upon modification of the cysteine residues in a highly conserved motif,
      CGWLCP, following TM4. Nonetheless, NosZ purified from the recombinant NosR
      background exhibited in vitro catalytic activity. Certain NosR derivatives caused
      an increase in NosZ of the spectral contribution from a modified catalytic Cu
      site. In addition to its role in nosZ expression, NosR supports in vivo N2O
      respiration. We also discuss its putative functions in electron donation and
      redox activation.

PMID- 15743948
TI  - Substrate specificities and expression patterns reflect the evolutionary
      divergence of maltose ABC transporters in Thermotoga maritima.
AB  - Duplication of transporter genes is apparent in the genome sequence of the
      hyperthermophilic bacterium Thermotoga maritima. The physiological impacts of
      these duplications are not well understood, so we used the bacterium's two
      putative maltose transporters to begin a study of the evolutionary relationship
      between a transporter's function and the control of expression of its genes. We
      show that the substrate binding proteins encoded by these operons, MalE1 and
      MalE2, have different substrate specificities and affinities and that they are
      expressed under different growth conditions. MalE1 binds maltose (dissociation
      constant [KD], 24 +/- 1 microM), maltotriose (KD, 8 +/- 0.5 nM), and beta-(1-->4)
      mannotetraose (KD, 38 +/- 1 microM). In contrast, MalE2 binds maltose (KD, 8.4 +/
      1 microM), maltotriose (KD, 11.5 +/- 1.5 microM), and trehalose (KD, 9.5 +/- 1.0
      microM) confirming the findings of Wassenberg et al. (J. Mol. Biol. 295:279-288,
      2000). Neither protein binds lactose. We examined the expression of these operons
      at both the transcriptional and translational levels and found that MalE1 is
      expressed in cells grown on lactose or guar gum and that MalE2 is highly
      expressed in starch- and trehalose-grown cells. Evidence is provided that malE1,
      malF1, and perhaps malG1 are cotranscribed and so constitute an operon. An open
      reading frame encoding a putative transcriptional regulatory protein adjacent to
      this operon (TM1200) is also up-regulated in response to growth on lactose. These
      evolutionarily related transporter operons have diverged both in function and
      expression to assume apparently different physiological roles.

PMID- 15743949
TI  - The Rok protein of Bacillus subtilis represses genes for cell surface and
      extracellular functions.
AB  - Rok is a repressor of the transcriptional activator ComK and is therefore an
      important regulator of competence in Bacillus subtilis (T. T. Hoa, P. Tortosa, M.
      Albano, and D. Dubnau, Mol. Microbiol. 43:15-26, 2002). To address the wider role
      of Rok in the physiology of B. subtilis, we have used a combination of
      transcriptional profiling, gel shift experiments, and the analysis of lacZ
      fusions. We demonstrate that Rok is a repressor of a family of genes that specify
      membrane-localized and secreted proteins, including a number of genes that encode
      products with antibiotic activity. We present evidence for the recent
      introduction of rok into the B. subtilis-Bacillus licheniformis-Bacilllus
      amyloliquefaciens group by horizontal transmission.

PMID- 15743950
TI  - Cytochrome bd oxidase, oxidative stress, and dioxygen tolerance of the strictly
      anaerobic bacterium Moorella thermoacetica.
AB  - The gram-positive, thermophilic, acetogenic bacterium Moorella thermoacetica can
      reduce CO2 to acetate via the Wood-Ljungdahl (acetyl coenzyme A synthesis)
      pathway. This report demonstrates that, despite its classification as a strict
      anaerobe, M. thermoacetica contains a membrane-bound cytochrome bd oxidase that
      can catalyze reduction of low levels of dioxygen. Whole-cell suspensions of M.
      thermoacetica had significant endogenous O2 uptake activity, and this activity
      was increased in the presence of methanol or CO, which are substrates in the Wood
      Ljungdahl pathway. Cyanide and azide strongly (approximately 70%) inhibited both
      the endogenous and CO/methanol-dependent O2 uptake. UV-visible light absorption
      and electron paramagnetic resonance spectra of n-dodecyl-beta-maltoside extracts
      of M. thermoacetica membranes showed the presence of a cytochrome bd oxidase
      complex containing cytochrome b561, cytochrome b595, and cytochrome d (chlorin).
      Subunits I and II of the bd oxidase were identified by N-terminal amino acid
      sequencing. The M. thermoacetica cytochrome bd oxidase exhibited cyanide
      sensitive quinol oxidase activity. The M. thermoacetica cytochrome bd (cyd)
      operon consists of four genes, encoding subunits I and II along with two ABC-type
      transporter proteins, homologs of which in other bacteria are required for
      assembly of the bd complex. The level of this cyd operon transcript was
      significantly increased when M. thermoacetica was grown in the absence of added
      reducing agent (cysteine + H2S). Expression of a 35-kDa cytosolic protein,
      identified as a cysteine synthase (CysK), was also induced by the nonreducing
      growth conditions. The combined evidence indicates that cytochrome bd oxidase and
      cysteine synthase protect against oxidative stress and contribute to the limited
      dioxygen tolerance of M. thermoacetica.

PMID- 15743951
TI  - A tetrahydrofolate-dependent O-demethylase, LigM, is crucial for catabolism of
      vanillate and syringate in Sphingomonas paucimobilis SYK-6.
AB  - Vanillate and syringate are converted into protocatechuate (PCA) and 3-O
      methylgallate (3MGA), respectively, by O-demethylases in Sphingomonas
      paucimobilis SYK-6. PCA is further degraded via the PCA 4,5-cleavage pathway,
      while 3MGA is degraded through multiple pathways in which PCA 4,5-dioxygenase
      (LigAB), 3MGA 3,4-dioxygenase (DesZ), and an unidentified 3MGA O-demethylase and
      gallate dioxygenase are participants. For this study, we isolated a 4.7-kb SmaI
      fragment that conferred on Escherichia coli the activity required for the
      conversion of vanillate to PCA. The nucleotide sequence of this fragment revealed
      an open reading frame of 1,413 bp (ligM), the deduced amino acid sequence of
      which showed 49% identity with that of the tetrahydrofolate (H4folate)-dependent
      syringate O-demethylase gene (desA). The metF and ligH genes, which are thought
      to be involved in H4folate-mediated C1 metabolism, were located just downstream
      of ligM. The crude LigM enzyme expressed in E. coli converted vanillate and 3MGA
      to PCA and gallate, respectively, with similar specific activities, and only in
      the presence of H4folate; however, syringate was not a substrate for LigM. The
      disruption of ligM led to significant growth retardation on both vanillate and
      syringate, indicating that ligM is involved in the catabolism of these
      substrates. The ability of the ligM mutant to transform vanillate was markedly
      decreased, and this mutant completely lost the 3MGA O-demethylase activity. A
      ligM desA double mutant completely lost the ability to transform vanillate, thus
      indicating that desA also contributes to vanillate degradation. All of these
      results indicate that ligM encodes vanillate/3MGA O-demethylase and plays an
      important role in the O demethylation of vanillate and 3MGA, respectively.

PMID- 15743952
TI  - CpxR/OmpR interplay regulates curli gene expression in response to osmolarity in
      Escherichia coli.
AB  - Curli fibers could be described as a virulence factor able to confer adherence
      properties to both abiotic and eukaryotic surfaces. The ability to adapt rapidly
      to changing environmental conditions through signal transduction pathways is
      crucial for the growth and pathogenicity of bacteria. OmpR was shown to activate
      csgD expression, resulting in curli production. The CpxR regulator was shown to
      negatively affect curli gene expression when binding to its recognition site that
      overlaps the csgD OmpR-binding site. This study was undertaken to clarify how the
      interplay between the two regulatory proteins, OmpR and CpxR, can affect the
      transcription of the curli gene in response to variation of the medium
      osmolarity. Band-shift assays with purified CpxR proteins indicate that CpxR
      binds to the csgD promoter region at multiple sites that are ideally positioned
      to explain the csg repression activity of CpxR. To understand the physiological
      meaning of this in vitro molecular phenomenon, we analyzed the effects of an
      osmolarity shift on the two-component pathway CpxA/CpxR. We establish here that
      the Cpx pathway is activated at both transcriptional and posttranscriptional
      levels in response to a high osmolarity medium and that CpxR represses csgD
      expression in high-salt-content medium, resulting in low curli production.
      However, csgD repression in response to high sucrose content is not mediated by
      CpxR but by the global regulatory protein H-NS. Therefore, multiple systems
      (EnvZ/OmpR, Cpx, Rcs, and H-NS) appear to be involved in sensing environmental
      osmolarity, leading to sophisticated regulation of the curli genes.

PMID- 15743953
TI  - Nucleotide sequence of the head assembly gene cluster of bacteriophage L and
      decoration protein characterization.
AB  - The temperate Salmonella enterica bacteriophage L is a close relative of the very
      well studied bacteriophage P22. In this study we show that the L procapsid
      assembly and DNA packaging genes, which encode terminase, portal, scaffold, and
      coat proteins, are extremely close relatives of the homologous P22 genes (96.3 to
      99.1% identity in encoded amino acid sequence). However, we also identify an L
      gene, dec, which is not present in the P22 genome and which encodes a protein
      (Dec) that is present on the surface of L virions in about 150 to 180
      molecules/virion. We also show that the Dec protein is a trimer in solution and
      that it binds to P22 virions in numbers similar to those for L virions. Its
      binding dramatically stabilizes P22 virions against disruption by a magnesium ion
      chelating agent. Dec protein binds to P22 coat protein shells that have expanded
      naturally in vivo or by sodium dodecyl sulfate treatment in vitro but does not
      bind to unexpanded procapsid shells. Finally, analysis of phage L restriction
      site locations and a number of patches of nucleotide sequence suggest that phages
      ST64T and L are extremely close relatives, perhaps the two closest relatives that
      have been independently isolated to date among the lambdoid phages.

PMID- 15743954
TI  - Magnesium promotes flagellation of Vibrio fischeri.
AB  - The bacterium Vibrio fischeri requires bacterial motility to initiate
      colonization of the Hawaiian squid Euprymna scolopes. Once colonized, however,
      the bacterial population becomes largely unflagellated. To understand
      environmental influences on V. fischeri motility, we investigated migration of
      this organism in tryptone-based soft agar media supplemented with different
      salts. We found that optimal migration required divalent cations and, in
      particular, Mg2+. At concentrations naturally present in seawater, Mg2+ improved
      migration without altering the growth rate of the cells. Transmission electron
      microscopy and Western blot experiments suggested that Mg2+ addition enhanced
      flagellation, at least in part through an effect on the steady-state levels of
      flagellin protein.

PMID- 15743955
TI  - Cyclic AMP (cAMP) and cAMP receptor protein influence both synthesis and uptake
      of extracellular autoinducer 2 in Escherichia coli.
AB  - Bacterial autoinducer 2 (AI-2) is proposed to be an interspecies mediator of cell
      cell communication that enables cells to operate at the multicellular level. Many
      environmental stimuli have been shown to affect the extracellular AI-2 levels,
      carbon sources being among the most important. In this report, we show that both
      AI-2 synthesis and uptake in Escherichia coli are subject to catabolite
      repression through the cyclic AMP (cAMP)-CRP complex, which directly stimulates
      transcription of the lsr (for "luxS regulated") operon and indirectly represses
      luxS expression. Specifically, cAMP-CRP is shown to bind to a CRP binding site
      located in the upstream region of the lsr promoter and works with the LsrR
      repressor to regulate AI-2 uptake. The functions of the lsr operon and its
      regulators, LsrR and LsrK, previously reported in Salmonella enterica serovar
      Typhimurium, are confirmed here for E. coli. The elucidation of cAMP-CRP
      involvement in E. coli autoinduction impacts many areas, including the growth of
      E. coli in fermentation processes.

PMID- 15743956
TI  - Characterization of a novel zinc-containing, lysine-specific aminopeptidase from
      the hyperthermophilic archaeon Pyrococcus furiosus.
AB  - Cell extracts of the proteolytic, hyperthermophilic archaeon Pyrococcus furiosus
      contain high specific activity (11 U/mg) of lysine aminopeptidase (KAP), as
      measured by the hydrolysis of L-lysyl-p-nitroanilide (Lys-pNA). The enzyme was
      purified by multistep chromatography. KAP is a homotetramer (38.2 kDa per
      subunit) and, as purified, contains 2.0 +/- 0.48 zinc atoms per subunit.
      Surprisingly, its activity was stimulated fourfold by the addition of Co2+ ions
      (0.2 mM). Optimal KAP activity with Lys-pNA as the substrate occurred at pH 8.0
      and a temperature of 100 degrees C. The enzyme had a narrow substrate specificity
      with di-, tri-, and tetrapeptides, and it hydrolyzed only basic N-terminal
      residues at high rates. Mass spectroscopy analysis of the purified enzyme was
      used to identify, in the P. furiosus genome database, a gene (PF1861) that
      encodes a product corresponding to 346 amino acids. The recombinant protein
      containing a polyhistidine tag at the N terminus was produced in Escherichia coli
      and purified using affinity chromatography. Its properties, including molecular
      mass, metal ion dependence, and pH and temperature optima for catalysis, were
      indistinguishable from those of the native form, although the thermostability of
      the recombinant form was dramatically lower than that of the native enzyme (half
      life of approximately 6 h at 100 degrees C). Based on its amino acid sequence,
      KAP is part of the M18 family of peptidases and represents the first prokaryotic
      member of this family. KAP is also the first lysine-specific aminopeptidase to be
      purified from an archaeon.

PMID- 15743957
TI  - Molecular analysis of the rebeccamycin L-amino acid oxidase from Lechevalieria
      aerocolonigenes ATCC 39243.
AB  - Rebeccamycin, a member of the tryptophan-derived indolocarbazole family, is
      produced by Lechevalieria aerocolonigenes ATCC 39243. The biosynthetic pathway
      that specifies biosynthesis of this important metabolite is comprised of 11 genes
      spanning 18 kb of DNA. A presumed early enzyme involved in elaboration of the
      rebeccamycin aglycone is encoded by rebO, located at the left-hand region of the
      reb gene cluster. The deduced protein product, RebO (51.9 kDa), is an L-amino
      acid oxidase (L-AAO) that has 27% identity to an L-AAO from Scomber japonicus
      (animal, mackerel) and is a member of the family of FAD-dependent oxidase
      enzymes. In order to study the biochemical properties of this key enzyme, the
      rebO gene was overexpressed and purified from Escherichia coli. Biochemical
      characterization showed that RebO is dimeric, with a molecular mass of
      approximately 101 kDa. Further analysis revealed that the enzyme contains a
      noncovalently bound FAD cofactor and is reoxidized at the expense of molecular
      oxygen by producing one molecule of hydrogen peroxide. Based on kinetic studies,
      RebO shows significant preference for 7-chloro-L-tryptophan, suggesting its
      likely role as the natural early pathway substrate. Furthermore, the native RebO
      enzyme has evident, albeit limited, flexibility as shown by bioconversion studies
      with unnatural substrates. This work provides the first analysis of a structural
      enzyme involved in construction of this important class of indolocarbazole
      natural products.

PMID- 15743958
TI  - Repression of the pyr operon in Lactobacillus plantarum prevents its ability to
      grow at low carbon dioxide levels.
AB  - Carbamoyl phosphate is a precursor for both arginine and pyrimidine biosynthesis.
      In Lactobacillus plantarum, carbamoyl phosphate is synthesized from glutamine,
      ATP, and carbon dioxide by two sets of identified genes encoding carbamoyl
      phosphate synthase (CPS). The expression of the carAB operon (encoding CPS-A)
      responds to arginine availability, whereas pyrAaAb (encoding CPS-P) is part of
      the pyrR1BCAaAbDFE operon coding for the de novo pyrimidine pathway repressed by
      exogenous uracil. The pyr operon is regulated by transcription attenuation
      mediated by a trans-acting repressor that binds to the pyr mRNA attenuation site
      in response to intracellular UMP/phosphoribosyl pyrophosphate pools.
      Intracellular pyrimidine triphosphate nucleoside pools were lower in mutant FB335
      (carAB deletion) harboring only CPS-P than in the wild-type strain harboring both
      CPS-A and CPS-P. Thus, CPS-P activity is the limiting step in pyrimidine
      synthesis. FB335 is unable to grow in the presence of uracil due to a lack of
      sufficient carbamoyl phosphate required for arginine biosynthesis. Forty
      independent spontaneous FB335-derived mutants that have lost regulation of the
      pyr operon were readily obtained by their ability to grow in the presence of
      uracil and absence of arginine; 26 harbored mutations in the pyrR1-pyrB loci. One
      was a prototroph with a deletion of both pyrR1 and the transcription attenuation
      site that resulted in large amounts of excreted pyrimidine nucleotides and
      increased intracellular UTP and CTP pools compared to wild-type levels. Low
      pyrimidine-independent expression of the pyr operon was obtained by
      antiterminator site-directed mutagenesis. The resulting AE1023 strain had reduced
      UTP and CTP pools and had the phenotype of a high-CO2-requiring auxotroph, since
      it was able to synthesize sufficient arginine and pyrimidines only in CO2
      enriched air. Therefore, growth inhibition without CO2 enrichment may be due to
      low carbamoyl phosphate pools from lack of CPS activity.

PMID- 15743959
TI  - Regulating pilin expression reveals a threshold for S motility in Myxococcus
      xanthus.
AB  - An isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible promoter was
      constructed in Myxococcus xanthus. The single-copy pilA gene encodes pilin, the
      monomer unit of M. xanthus type IV pili. To vary the level of pilA expression, we
      cloned its promoter in front of the lac operator, and a plasmid containing the
      construct was inserted into the chromosome of a DeltapilA strain. Induction of
      pilin expression increased smoothly as the dose of IPTG added to the culture was
      increased. IPTG-induced pilin rescued S motility of the DeltapilA strain to wild
      type levels. The rate of S-motile swarming was found to be proportional to the
      number of pili (shear-sensitive pilin) produced rather than to the level of total
      pilin. In fact, S motility was not rescued until the total level of pilin was
      more than 50% of the wild-type level. This observation implies that a threshold
      concentration of pilin must be exceeded before the shear-sensitive material
      (pili) is polymerized in M. xanthus.

PMID- 15743960
TI  - Comparative genomic analysis of the pPT23A plasmid family of Pseudomonas
      syringae.
AB  - Members of the pPT23A plasmid family of Pseudomonas syringae play an important
      role in the interaction of this bacterial pathogen with host plants. Complete
      sequence analysis of several pPT23A family plasmids (PFPs) has provided a glimpse
      of the gene content and virulence function of these plasmids. We constructed a
      macroarray containing 161 genes to estimate and compare the gene contents of 23
      newly analyzed and eight known PFPs from 12 pathovars of P. syringae, which
      belong to four genomospecies. Hybridization results revealed that PFPs could be
      distinguished by the type IV secretion system (T4SS) encoded and separated into
      four groups. Twelve PFPs along with pPSR1 from P. syringae pv. syringae, pPh1448B
      from P. syringae pv. phaseolicola, and pPMA4326A from P. syringae pv. maculicola
      encoded a type IVA T4SS (VirB-VirD4 conjugative system), whereas 10 PFPs along
      with pDC3000A and pDC3000B from P. syringae pv. tomato encoded a type IVB T4SS
      (tra system). Two plasmids encoded both T4SSs, whereas six other plasmids carried
      none or only a few genes of either the type IVA or type IVB secretion system.
      Most PFPs hybridized to more than one putative type III secretion system effector
      gene and to a variety of additional genes encoding known P. syringae virulence
      factors. The overall gene contents of individual PFPs were more similar among
      plasmids within each of the four groups based on T4SS genes; however, a number of
      genes, encoding plasmid-specific functions or hypothetical proteins, were shared
      among plasmids from different T4SS groups. The only gene shared by all PFPs in
      this study was the repA gene, which encoded sequences with 87 to 99% amino acid
      identityamong 25 sequences examined. We proposed a model to illustrate the
      evolution and gene acquisition of the pPT23A plasmid family. To our knowledge,
      this is the first such attempt to conduct a global genetic analysis of this
      important plasmid family.

PMID- 15743961
TI  - Simultaneous force and fluorescence measurements of a protein that forms a bond
      between a living bacterium and a solid surface.
AB  - All microbial biofilms are initiated through direct physical contact between a
      bacterium and a solid surface, a step that is controlled by inter- and
      intramolecular forces. Atomic force microscopy and confocal laser scanning
      microscopy were used simultaneously to observe the formation of a bond between a
      fluorescent chimeric protein on the surface of a living Escherichia coli
      bacterium and a solid substrate in situ. The chimera was composed of a portion of
      outer membrane protein A (OmpA) fused to the cyan-fluorescent protein AmCyan.
      Sucrose gradient centrifugation and fluorescent confocal slices through bacteria
      demonstrated that the chimeric protein was targeted and anchored to the external
      cell surface. The wormlike chain theory predicted that this protein should
      exhibit a nonlinear force-extension "signature" consistent with the sequential
      unraveling of the AmCyan and OmpA domains. Experimentally measured force
      extension curves revealed a unique pair of "sawtooth" features that were present
      when a bond formed between a silicon nitride surface (atomic force microscopy
      tip) and E. coli cells expressing the OmpA-AmCyan protein. The observed sawtooth
      pair closely matched the wormlike chain model prediction for the mechanical
      unfolding of the AmCyan and OmpA substructures in series. These sawteeth
      disappeared from the measured force-extension curves when cells were treated with
      proteinase K. Furthermore, these unique sawteeth were absent for a mutant stain
      of E. coli incapable of expressing the AmCyan protein on its outer surface.
      Together, these data show that specific proteins exhibit unique force signatures
      characteristic of the bond that is formed between a living bacterium and another
      surface.

PMID- 15743962
TI  - Evidence for diversifying selection at the pyoverdine locus of Pseudomonas
      aeruginosa.
AB  - Pyoverdine is the primary siderophore of the gram-negative bacterium Pseudomonas
      aeruginosa. The pyoverdine region was recently identified as the most divergent
      locus alignable between strains in the P. aeruginosa genome. Here we report the
      nucleotide sequence and analysis of more than 50 kb in the pyoverdine region from
      nine strains of P. aeruginosa. There are three divergent sequence types in the
      pyoverdine region, which correspond to the three structural types of pyoverdine.
      The pyoverdine outer membrane receptor fpvA may be driving diversity at the
      locus: it is the most divergent alignable gene in the region, is the only gene
      that showed substantial intratype variation that did not appear to be generated
      by recombination, and shows evidence of positive selection. The hypothetical
      membrane protein PA2403 also shows evidence of positive selection; residues on
      one side of the membrane after protein folding are under positive selection. R',
      previously identified as a type IV strain, is clearly derived from a type III
      strain via a 3.4-kb deletion which removes one amino acid from the pyoverdine
      side chain peptide. This deletion represents a natural modification of the
      product of a nonribosomal peptide synthetase enzyme, whose consequences are
      predictive from the DNA sequence. There is also linkage disequilibrium between
      the pyoverdine region and pvdY, a pyoverdine gene separated by 30 kb from the
      pyoverdine region. The pyoverdine region shows evidence of horizontal transfer;
      we propose that some alleles in the region were introduced from other soil
      bacteria and have been subsequently maintained by diversifying selection.

PMID- 15743963
TI  - Transcriptome analysis of the Rhodobacter sphaeroides PpsR regulon: PpsR as a
      master regulator of photosystem development.
AB  - PpsR from the anoxygenic phototrophic bacterium Rhodobacter sphaeroides has been
      known as an oxygen- and light-dependent repressor of bacteriochlorophyll and
      carotenoid biosynthesis genes and puc operons involved in photosystem
      development. However, the putative PpsR-binding sites, TGTN12ACA, are also
      located upstream of numerous nonphotosystem genes, thus raising the possibility
      that the role of PpsR is broader. To characterize the PpsR regulon, transcriptome
      profiling was performed on the wild-type strain grown at high and low oxygen
      tensions, on the strain overproducing PpsR, and on the ppsR mutant. Transcriptome
      analysis showed that PpsR primarily regulates photosystem genes; the consensus
      PpsR binding sequence is TGTcN10gACA (lowercase letters indicate lesser
      conservation); the presence of two binding sites is required for repression in
      vivo. These findings explain why numerous single TGTN12ACA sequences are
      nonfunctional. In addition to photosystem genes, the hemC and hemE genes involved
      in the early steps of tetrapyrrole biosynthesis were identified as new direct
      targets of PpsR repression. Unexpectedly, PpsR was found to indirectly repress
      the puf and puhA operons encoding photosystem core proteins. The upstream regions
      of these operons contain no PpsR binding sites. Involvement in regulation of
      these operons suggests that PpsR functions as a master regulator of photosystem
      development. Upregulation of the puf and puhA operons that resulted from ppsR
      inactivation was sufficient to restore the ability to grow phototrophically to
      the prrA mutant. PrrA, the global redox-dependent activator, was previously
      considered indispensable for phototrophic growth. It is revealed that the PrrBA
      and AppA-PpsR systems, believed to work independently, in fact interact and
      coordinately regulate photosystem development.

PMID- 15743964
TI  - Role of the PhoP-PhoQ system in the virulence of Erwinia chrysanthemi strain
      3937: involvement in sensitivity to plant antimicrobial peptides, survival at
      acid Hh, and regulation of pectolytic enzymes.
AB  - Erwinia chrysanthemi is a phytopathogenic bacterium that causes soft-rot diseases
      in a broad number of crops. The PhoP-PhoQ system is a key factor in pathogenicity
      of several bacteria and is involved in the bacterial resistance to different
      factors, including acid stress. Since E. chrysanthemi is confronted by acid pH
      during pathogenesis, we have studied the role of this system in the virulence of
      this bacterium. In this work, we have isolated and characterized the phoP and
      phoQ mutants of E. chrysanthemi strain 3937. It was found that: (i) they were not
      altered in their growth at acid pH; (ii) the phoQ mutant showed diminished
      ability to survive at acid pH; (iii) susceptibility to the antimicrobial peptide
      thionin was increased; (iv) the virulence of the phoQ mutant was diminished at
      low and high magnesium concentrations, whereas the virulence of the phoP was
      diminished only at low magnesium concentrations; (v) in planta Pel activity of
      both mutant strains was drastically reduced; and (vi) both mutants lagged behind
      the wild type in their capacity to change the apoplastic pH. These results
      suggest that the PhoP-PhoQ system plays a role in the virulence of this bacterium
      in plant tissues, although it does not contribute to bacterial growth at acid pH.

PMID- 15743965
TI  - Phosphatidylethanolamine domains and localization of phospholipid synthases in
      Bacillus subtilis membranes.
AB  - Application of the cardiolipin (CL)-specific fluorescent dye 10-N-nonyl-acridine
      orange has recently revealed CL-rich domains in the septal regions and at the
      poles of the Bacillus subtilis membrane (F. Kawai, M. Shoda, R. Harashima, Y.
      Sadaie, H. Hara, and K. Matsumoto, J. Bacteriol. 186:1475-1483, 2004). This
      finding prompted us to examine the localization of another phospholipid,
      phosphatidylethanolamine (PE), with the cyclic peptide probe, Ro09-0198 (Ro),
      that binds specifically to PE. Treatment with biotinylated Ro followed by
      tetramethyl rhodamine-conjugated streptavidin revealed that PE is localized in
      the septal membranes of vegetative cells and in the membranes of the polar septum
      and the engulfment membranes of sporulating cells. When the mutant cells of the
      strains SDB01 (psd1::neo) and SDB02 (pssA10::spc), which both lack PE, were
      examined under the same conditions, no fluorescence was observed. The
      localization of the fluorescence thus evidently reflected the localization of PE
      rich domains in the septal membranes. Similar PE-rich domains were observed in
      the septal regions of the cells of many Bacillus species. In Escherichia coli
      cells, however, no PE-rich domains were found. Green fluorescent protein fusions
      to the enzymes that catalyze the committed steps in PE synthesis,
      phosphatidylserine synthase, and in CL synthesis, CL synthase and
      phosphatidylglycerophosphate synthase, were localized mainly in the septal
      membranes in B. subtilis cells. The majority of the lipid synthases were also
      localized in the septal membranes; this includes 1-acyl-glycerol-3-phosphate
      acyltransferase, CDP-diacylglycerol synthase, phosphatidylserine decarboxylase,
      diacylglycerol kinase, glucolipid synthase, and lysylphosphatidylglycerol
      synthase. These results suggest that phospholipids are produced mostly in the
      septal membranes and that CL and PE are kept from diffusing out to lateral ones.

PMID- 15743966
TI  - Crystal structure of low-molecular-weight protein tyrosine phosphatase from
      Mycobacterium tuberculosis at 1.9-A resolution.
AB  - The low-molecular-weight protein tyrosine phosphatase (LMWPTPase) belongs to a
      distinctive class of phosphotyrosine phosphatases widely distributed among
      prokaryotes and eukaryotes. We report here the crystal structure of LMWPTPase of
      microbial origin, the first of its kind from Mycobacterium tuberculosis. The
      structure was determined to be two crystal forms at 1.9- and 2.5-A resolutions.
      These structural forms are compared with those of the LMWPTPases of eukaryotes.
      Though the overall structure resembles that of the eukaryotic LMWPTPases, there
      are significant changes around the active site and the protein tyrosine
      phosphatase (PTP) loop. The variable loop forming the wall of the crevice leading
      to the active site is conformationally unchanged from that of mammalian
      LMWPTPase; however, differences are observed in the residues involved, suggesting
      that they have a role in influencing different substrate specificities. The
      single amino acid substitution (Leu12Thr [underlined below]) in the consensus
      sequence of the PTP loop, CTGNICRS, has a major role in the stabilization of the
      PTP loop, unlike what occurs in mammalian LMWPTPases. A chloride ion and a
      glycerol molecule were modeled in the active site where the chloride ion
      interacts in a manner similar to that of phosphate with the main chain nitrogens
      of the PTP loop. This structural study, in addition to identifying specific
      mycobacterial features, may also form the basis for exploring the mechanism of
      the substrate specificities of bacterial LMWPTPases.

PMID- 15743967
TI  - Environmental pH sensing: resolving the VirA/VirG two-component system inputs for
      Agrobacterium pathogenesis.
AB  - Agrobacterium tumefaciens stands as one of biotechnology's greatest successes,
      with all plant genetic engineering building on the strategies of this pathogen.
      By integrating responses to external pHs, phenols, and monosaccharides, this
      organism mobilizes oncogenic elements to efficiently transform most
      dicotyledonous plants. We now show that the complex signaling network used to
      regulate lateral gene transfer can be resolved as individual signaling modules.
      While pH and sugar perception are coupled through a common pathway, requiring
      both low pH and sugar for maximal virulence gene expression, various VirA and
      ChvE alleles can decouple pH and monosaccharide perception. This VirA and ChvE
      system may represent a common mechanism that underpins external pH perception in
      prokaryotes, and the use of these simple genetic elements may now be extended to
      research on specific responses to changes in environmental pH.

PMID- 15743969
TI  - A mutation in the decoding center of Thermus thermophilus 16S rRNA suggests a
      novel mechanism of streptomycin resistance.
AB  - A spontaneous kanamycin resistance and capreomycin resistance mutation, A1408G,
      in the decoding center of 16S rRNA, was identified in the extreme thermophile
      Thermus thermophilus. Unexpectedly, this mutation also confers resistance to
      streptomycin. We propose a novel mechanism of streptomycin resistance by which
      A1408G influences conformational changes in 16S rRNA during tRNA selection.

PMID- 15743968
TI  - Global analysis of circadian expression in the cyanobacterium Synechocystis sp.
      strain PCC 6803.
AB  - Cyanobacteria are the only bacterial species found to have a circadian clock. We
      used DNA microarrays to examine circadian expression patterns in the
      cyanobacterium Synechocystis sp. strain PCC 6803. Our analysis identified 54 (2%)
      and 237 (9%) genes that exhibited circadian rhythms under stringent and relaxed
      filtering conditions, respectively. The expression of most cycling genes peaked
      around the time of transition from subjective day to night, suggesting that the
      main role of the circadian clock in Synechocystis is to adjust the physiological
      state of the cell to the upcoming night environment. There were several
      chromosomal regions where neighboring genes were expressed with similar circadian
      patterns. The physiological functions of the cycling genes were diverse and
      included a wide variety of metabolic pathways, membrane transport, and signal
      transduction. Genes involved in respiration and poly(3-hydroxyalkanoate)
      synthesis showed coordinated circadian expression, suggesting that the regulation
      is important for the supply of energy and carbon source in the night. Genes
      involved in transcription and translation also followed circadian cycling
      patterns. These genes may be important for output of the rhythmic information
      generated by the circadian clock. Our findings provided critical insights into
      the importance of the circadian clock on cellular physiology and the mechanism of
      clock-controlled gene regulation.

PMID- 15743970
TI  - Lateral gene transfer of dissimilatory (bi)sulfite reductase revisited.
AB  - In contrast to previous findings, we demonstrate that the dissimilatory
      (bi)sulfite reductase genes (dsrAB) of Desulfobacula toluolica were vertically
      inherited. Furthermore, Desulfobacterium anilini and strain mXyS1 were
      identified, by dsrAB sequencing of 17 reference strains, as members of the donor
      lineage for those gram-positive Desulfotomaculum species which laterally acquired
      dsrAB.

PMID- 15743971
TI  - Plasmid- and chromosome-encoded redundant and specific functions are involved in
      biosynthesis of the siderophore anguibactin in Vibrio anguillarum 775: a case of
      chance and necessity?
AB  - We report the identification of a novel chromosome cluster of genes in Vibrio
      anguillarum 775 that includes redundant functional homologues of the pJM1 plasmid
      harbored genes angE and angC that are involved in anguibactin biosynthesis. We
      also identified in this cluster a chromosomal angA gene that is essential in
      anguibactin biosynthesis.

PMID- 15743972
TI  - Kinetic characterization of the glycosyltransferase module of Staphylococcus
      aureus PBP2.
AB  - We report the heterologous overexpression and purification of Staphylococcus
      aureus PBP2 and demonstrate efficient glycan polymerization from lipid II in
      vitro. S. aureus PBP2 is the first purified gram-positive class A penicillin
      binding protein to show good transglycosylase activity. This enables further
      studies on this important class of enzymes.

PMID- 15743973
TI  - Influence of amino acid substitutions in the leader peptide on maturation and
      secretion of mesentericin Y105 by Leuconostoc mesenteroides.
AB  - By site-specific mutagenesis, the hydrophobic conserved amino acids and the C
      terminal GG doublet of the leader peptide of pre-mesentericin Y105 were
      demonstrated to be critical for optimal secretion of mesentericin Y105, as well
      as for the maturation of the pre-bacteriocin by the protease portion of the ABC
      transporter MesD.

PMID- 15743975
TI  - In vitro metabolism study of buprenorphine: evidence for new metabolic pathways.
AB  - Buprenorphine (BUP) is a synthetic derivative of the morphine alkaloid thebaine.
      BUP is metabolized by N-dealkylation to form the active metabolite nor
      buprenorphine (Nor-BUP), and both undergo subsequent glucuronidation. Although
      BUP has been used clinically for years, its metabolism has still not been fully
      elucidated. The aim of this study was to clarify the identity of the human
      hepatic cytochromes P450 (P450s) involved in BUP metabolism and to investigate
      other potential metabolites. The metabolism of BUP was examined using human liver
      microsomes (HLM) and Ad293 P450-transfected cell lines, as well as CYP 3A4 and
      2C8 recombinant isoforms. The kinetic parameters of metabolite formation were
      calculated for HLM and competent isoforms. Individual contribution of P450
      isoforms in BUP metabolism as well as Nor-BUP production was evaluated using
      chemical inhibition experiments, as well as the relative activity factor
      approach. The analytical method used was based on liquid chromatography-mass
      spectrometry. Among the 13 P450 isoforms tested, CYP 3A4, 2C8, 3A5, and 3A7
      produced Nor-BUP. Based on the results of chemical inhibition, CYP 3A4 accounts
      for about 65% of Nor-BUP production and CYP 2C8 for about 30%. BUP utilization by
      either HLM or P450-transfected cells revealed that another oxidative metabolic
      pathway exists, which was found to involve CYP 2C9, 2C18, 2C19, and mainly CYP
      3A. Incubation of BUP or Nor-BUP with HLM led to the formation of new
      metabolites, identified by tandem mass spectrometry as being hydroxy-BUP and
      hydroxy-Nor-BUP. Hydroxy-BUP was produced by the CYP 3A, but not the 2C isoforms.

PMID- 15743974
TI  - RGG-boxes of the EWS oncoprotein repress a range of transcriptional activation
      domains.
AB  - The Ewings Sarcoma Oncoprotein (EWS) interacts with several components of the
      mammalian transcriptional and pre-mRNA splicing machinery and is also found in
      the cytoplasm and even on the cell surface. The apparently diverse cellular
      functions of EWS are, however, not well characterized. EWS harbours a potent N
      terminal transcriptional activation domain (the EAD) that is revealed in the
      context of oncogenic EWS-fusion proteins (EFPs) and a C-terminal RNA-binding
      domain (RBD) that recruits pre-mRNA splicing factors and may couple transcription
      and splicing. In contrast to EFPs, the presumed transcriptional role of normal
      EWS remains enigmatic. Here, we report that multiple RGG-boxes within the RBD are
      necessary and sufficient for cis-repression of the EAD and that RGG-boxes can
      also repress in-trans, within dimeric partners. Lys can functionally substitute
      for Arg, indicating that the basic nature of the Arg side chain is the critical
      determinant of RGG-box-mediated repression. In addition to the EAD, RGG-boxes can
      repress a broad range of activation domains (including those of VP16, E1a and
      CREB), but repression can be alleviated by the simultaneous presence of more than
      one activation domain. We therefore propose that a key function of RGG boxes
      within native EWS is to restrict promiscuous activation by the EAD while still
      allowing EWS to enter functional transcription complexes and participate in other
      transactions involving pre-mRNAs.

PMID- 15743976
TI  - Functional analysis of the human variants of breast cancer resistance protein:
      I206L, N590Y, and D620N.
AB  - Previous studies have shown that the V12M and Q141K variants of breast cancer
      resistance protein (BCRP) can affect expression and function of the transporter.
      In this study, the effects of the I206L, N590Y, and D620N variants on protein
      expression, plasma membrane localization, and transport activity of BCRP were
      investigated. Wild-type BCRP and the three variants were stably expressed in
      human embryonic kidney (HEK) cells. Confocal microscopy analysis showed that the
      three variants were predominantly routed to the plasma membrane of HEK cells. The
      expression level of I206L in the plasma membrane was approximately 45% of that of
      wild-type protein, whereas the N590Y and D620N levels were increased
      approximately 3.6-fold and 2.4-fold, respectively, as determined by
      immunoblotting. All three variants transported mitoxantrone, pheophorbide a, and
      BODIPY FL-prazosin. After normalization for differences in BCRP expression,
      I206L, N590Y, and D620N exhibited approximately 2-fold, 0.3-fold, and 0.5-fold
      wild-type efflux activities, respectively. The variants also conferred resistance
      to mitoxantrone and topotecan. Mitoxantrone and topotecan resistance by I206L and
      N590Y was approximately 2-fold and 0.3-fold of the wild-type BCRP resistance
      levels, respectively. Although D620N conferred a topotecan resistance similar to
      that of the wild-type protein, its level of mitoxantrone resistance was decreased
      by 50%. After normalization to BCRP expression levels, ATPase activities of I206L
      were not significantly different from those of wild-type protein, whereas N590Y
      and D620N exhibited approximately 30% and 50% of wild-type ATPase activities,
      respectively. These results suggest that I206L has the lowest protein expression
      and the highest activity, whereas N590Y and D620N display higher expression and
      lower activity, relative to wild-type BCRP.

PMID- 15743977
TI  - Evaluation of time-dependent inactivation of CYP3A in cryopreserved human
      hepatocytes.
AB  - Irreversible CYP3A inhibition by drugs constitutes one of the major causes of
      inhibition-based drug interactions. We evaluated time-dependent inactivation of
      CYP3A in cryopreserved human hepatocytes for six structurally diverse compounds
      known to exhibit this property. Inactivation kinetic parameters were also
      determined using human liver microsomes. Except for diclofenac, which did not
      cause CYP3A inactivation either in microsomes or in hepatocytes at concentrations
      up to 100 microM, time-dependent inactivation was observed in hepatocytes for
      amprenavir, diltiazem, erythromycin, raloxifene, and troleandomycin. The observed
      inactivation potency in hepatocytes (observed IC50) was compared with the potency
      predicted using microsomal parameters (predicted IC50). Despite satisfactory
      prediction for troleandomycin (1.35 and 2.14 microM for the predicted and
      observed IC50, respectively), over-prediction of inactivation was observed for
      raloxifene, amprenavir, and erythromycin (observed IC50 values 6.2-, 55-, and 7.8
      fold higher, respectively, than the predicted IC50). By contrast, the observed
      IC50 for diltiazem in hepatocytes was approximately 4-fold lower than the IC50
      predicted from microsomal data (under-prediction). After correcting for factors
      including nonspecific binding and inactivator consumption, prediction was
      significantly improved for raloxifene (the observed IC50 then became 2-fold
      higher than the predicted IC50) and for amprenavir to a lesser extent. A specific
      P-glycoprotein inhibitor, 4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-[2
      (3.4-dimethoxyphenyl)ethyl]-6,7-dimethoxyquinazolin-2-amine (CP-100356),
      modulated the observed CYP3A inactivation potency by erythromycin and
      troleandomycin. In summary, these studies reveal three important factors that
      must be considered when microsomal inactivation parameters are used to predict
      inhibition-based drug interactions in intact cell systems.

PMID- 15743978
TI  - The distribution, metabolism, and elimination of clofarabine in rats.
AB  - The distribution, metabolism, and elimination of intravenous [14C]clofarabine was
      studied in Fischer 344 male rats under a once daily for 5 days dosing schedule of
      25 or 50 mg/kg/day. Also, the in vitro metabolism in rat, dog, and human
      hepatocytes was studied. Plasma radioactivity (of which clofarabine accounted for
      63% to 93%) exhibited three phases of exponential elimination, with half-lives of
      0.3, 1.3, and 12.8 h after administration of the 25 mg/kg/day regimen.
      Unscheduled deaths occurred after one to three doses with the 50 mg/kg regimen,
      possibly due to nonlinear pharmacokinetics; therefore, mass balance and
      radiokinetic profiles could not be obtained. A total of 77.1% (of which 87.2% was
      clofarabine) and 10.8% (of which 6.9% was clofarabine) of the dose was recovered
      in urine and feces, respectively. 6-ketoclofarabine, believed to be formed via
      adenosine deaminase, was the metabolite of greatest concentration found in urine
      and feces, but in each matrix, it accounted for only 7% of the daily recovery of
      radioactivity. 6-ketoclofarabine was also found in myocardium and liver but
      accounted for less than 2% of the total radioactivity in those tissues.
      Clofarabine was the major analyte found in myocardium (>97% region of
      integration) and liver (>94% region of integration). Whole body autoradiography
      demonstrated that the highest postdistributive concentrations of radioactivity
      were in the excretory organs, kidney, bladder, and gastrointestinal tract, with
      no remarkable suborgan distribution. In rat, dog, and human hepatocytes, 95, 96,
      and 99.8% [14C]clofarabine remained, respectively, after 6 h of incubation.
      Eleven metabolites were observed, with the largest constituting 2.5% of the
      radioactivity.

PMID- 15743979
TI  - Nonlinear pharmacokinetics of propafenone in rats and humans: application of a
      substrate depletion assay using hepatocytes for assessment of nonlinearity.
AB  - Linear pharmacokinetic profiles of propafenone in female Wistar rats were found
      after oral administration of up to 20 mg/kg. These profiles differed from
      nonlinear pharmacokinetics in a dose-dependent manner with increasing plasma
      concentrations in humans (Hollmann M, Brode E, Hotz D, Kaumeier S, and Kehrhahn
      OH (1983) Arzneim-Forsch 33:763-770). We investigated the species differences in
      pharmacokinetics of propafenone between rats and humans. In rats, after
      intravenous administration, clearance was constant at all doses examined (0.2-10
      mg/kg), whereas the distribution volume at a steady state increased and the
      resultant elimination half-life was prolonged with increasing doses. In a
      substrate depletion assay without plasma, rat and human hepatocytes showed a
      concentration-dependent elimination of propafenone with low Km values (<0.4
      microM). However, in the depletion assay with plasma incubation, the profiles
      were altered to a concentration-independent profile in rat but not human
      hepatocytes. The differing effect of adding plasma in rat and human hepatocytes
      can be explained by species differences in plasma binding (unbound fraction,
      0.0071 versus 0.0754 for rats and humans, respectively, at 0.1 microg/ml). In rat
      plasma, the unbound fraction increased with concentrations of 0.1 to 1.0
      microg/ml, whereas it was constant in human plasma. Accordingly, the in vivo
      nonlinear disposition in humans can be ascribed to the saturation of hepatic
      metabolism due to the low Km values. In contrast, the influence of saturable
      metabolism is canceled out with nonlinear plasma binding in rats leading to the
      apparent linear pharmacokinetic behavior. The newly developed depletion assay
      with plasma incubation gave insights into the nonlinear pharmacokinetics of
      propafenone.

PMID- 15743980
TI  - Identity and emergency intervention: how social group membership and
      inclusiveness of group boundaries shape helping behavior.
AB  - Two experiments exploring the effects of social category membership on real-life
      helping behavior are reported. In Study 1, intergroup rivalries between soccer
      fans are used to examine the role of identity in emergency helping. An injured
      stranger wearing an in-group team shirt is more likely to be helped than when
      wearing a rival team shirt or an unbranded sports shirt. In Study 2, a more
      inclusive social categorization is made salient for potential helpers. Helping is
      extended to those who were previously identified as out-group members but not to
      those who do not display signs of group membership. Taken together, the studies
      show the importance of both shared identity between bystander and victim and the
      inclusiveness of salient identity for increasing the likelihood of emergency
      intervention.

PMID- 15743981
TI  - Forecasting one's future based on fleeting subjective experiences.
AB  - When we forecast our futures, to what extent do we rely on explicit and concrete
      facts versus implicit and fleeting subjective experiences? Results from two
      studies reveal that forecasting judgments hinge on at least two fleeting
      experiences: the specific incidental emotions one happens to feel at the time of
      forming a judgment and the subjective ease-of-thought-generation. Results also
      reveal that imposing accountability for the accuracy of one's forecast provides
      no simple remedy. Incidental emotions, the ease-of-thought-generation, and
      accountability combine multiplicatively in a three-way interaction. Although
      accountability attenuates the respective effects of incidental fear and
      incidental anger, doing so has the undesirable effect of amplifying the ease-of
      thought-generation effects that fear otherwise suppresses. In no instance does
      accountability completely eliminate the unintended effects of these fleeting
      subjective experiences. Discussion addresses implications for theories of affect
      and social cognition as well as for applications to risk perception.

PMID- 15743982
TI  - Comparisons and perceived deprivation in ethnic minority settings.
AB  - Two studies investigated comparison choices among ethnic minorities and
      majorities. The perceived status of the self vis-a-vis different comparison
      targets also was assessed. Antecedents and consequences of comparisons and
      relative deprivation were examined. Predictions were derived from social
      comparison, stigma, social identity, and relative deprivation research. Two
      surveys were conducted, one in London with mainly Asian participants (N = 235)
      and one in Germany with Turkish and Aussiedler participants (N = 166) and German
      majority members (N = 351). Participants preferred intragroup and temporal
      comparisons (with other ingroup members and with the self in the past) to various
      types of cross-group comparisons (with outgroup members). Perceived similarity
      and contact with a target positively predicted interest in comparing with this
      target, and perceived higher status of the target was a negative predictor. Some
      evidence was found that feelings of deprivation depend on comparison choices.
      Deprivation negatively predicted self-esteem and life satisfaction. Deprivation
      and group identification were negatively correlated.

PMID- 15743983
TI  - Stereotypes and the confirmability of trait concepts.
AB  - Two studies tested the hypothesis that rules of trait inference may differ
      depending on trait stereotypicality and the social group membership of the target
      being judged. Specifically, traits that are stereotypic of a group were expected
      to instantiate lower evidentiary standards (require fewer behaviors to confirm),
      but only in members of that group. Study 1 focused on race and found that across
      180 traits, trait stereotypicality was associated with fewer behaviors required
      to confirm and more to disconfirm in outgroup targets (in Black actors for White
      judges and in White actors for Black judges). Study 2 focused on gender and again
      found that stereotypic traits were tied to low evidentiary standards only when
      judging outgroup targets. The findings are discussed with reference to the
      literatures on trait inference, stereotyping, and shifting judgment standards.

PMID- 15743984
TI  - Stigmatized targets and evaluation: prejudice as a determinant of attribute
      scrutiny and polarization.
AB  - The authors provide evidence for a new mechanism for the more polarized
      evaluations of stigmatized than nonstigmatized target individuals that often
      follow positive versus negative target descriptions. The current research
      suggests that polarization can occur because low-prejudiced perceivers think more
      about information describing stigmatized than nonstigmatized targets (i.e., have
      polarized thoughts). Mediational path analyses revealed that polarized thoughts
      fully accounted for the impact of prejudice on evaluative polarization. These
      findings are most consistent with the watchdog hypothesis that people scrutinize
      information describing stigmatized targets in order to guard against possibly
      unfair reactions by themselves or others.

PMID- 15743985
TI  - Inequality as ingroup privilege or outgroup disadvantage: the impact of group
      focus on collective guilt and interracial attitudes.
AB  - Among members of privileged groups, social inequality is often thought of in
      terms of the disadvantages associated with outgroup membership. Yet inequality
      also can be validly framed in terms of ingroup privilege. These different
      framings have important psychological and social implications. In Experiment 1 (N
      = 110), White American participants assessed 24 statements about racial
      inequality framed as either White privileges or Black disadvantages. In
      Experiment 2 (N = 122), White participants generated examples of White privileges
      or Black disadvantages. In both experiments, a White privilege framing resulted
      in greater collective guilt and lower racism compared to a Black disadvantage
      framing. Collective guilt mediated the manipulation's effect on racism. In
      addition, in Experiment 2, a White privilege framing decreased White racial
      identification compared to a Black disadvantage framing. These findings suggest
      that representing inequality in terms of outgroup disadvantage allows privileged
      group members to avoid the negative psychological implications of inequality and
      supports prejudicial attitudes.

PMID- 15743986
TI  - The link between religion and spirituality and psychological adjustment: the
      mediating role of optimism and social support.
AB  - Although optimism, social support, religiousness, and spirituality are important
      predictors of adjustment, rarely have studies examined these variables
      simultaneously. This study investigated whether optimism and social support
      mediated the relationship between religiousness and adjustment (distress and life
      satisfaction) and between spirituality and adjustment. Findings indicate that the
      relationship between intrinsic religiousness and life satisfaction and between
      prayer fulfillment and life satisfaction was mediated by optimism and social
      support. Furthermore, the relationship between religiousness and adjustment
      varied depending on how religiousness was operationalized and whether positive
      versus negative adjustment indicators were used. That is, intrinsic religiousness
      and prayer fulfillment were associated with greater life satisfaction, but
      extrinsic religiousness was not associated with life satisfaction. These findings
      were significant even after accounting for covariates (age, gender, ethnicity,
      social desirability). Results suggest religiousness and spirituality are related
      but distinct constructs and are associated with adjustment through factors such
      as social support and optimism.

PMID- 15743987
TI  - "A picture's worth a thousand words": language use in the autophotographic essay.
AB  - The authors applied Pennebaker's Linguistic Inquiry and Word Count (LIWC) program
      to autophotographic essays addressing the question, "Who are you?" to test
      hypotheses about individuality and social connectedness. Specifically, the
      authors tested whether insight-oriented words would correlate with individuality
      ratings, defining essays that portray unique persons who creatively explore the
      self. Second, the authors tested whether connectedness, operationalized by photos
      of people-touching and self with others, would correlate with social process
      words. In 164 student photo essays, greater linguistic cognitive complexity
      characterized individuality, even when controlling for needs for cognition and
      uniqueness, and verbal intelligence. Connectedness predicted social words. These
      findings show that autophotography essays do capture complex self-reflective
      thought and suggest LIWC may be a valuable tool for understanding the expression
      of individuality and relatedness.

PMID- 15743988
TI  - Applying the interpersonal circumplex to children's behavior: parent-child
      interactions and risk behaviors.
AB  - This article examined the applicability of the interpersonal circumplex (IC) to
      the observable social behaviors of children during parent-child interactions. In
      Study 1, the observational ratings of behaviors of 117 children (mean age = 9.88
      years) were examined. Randomization tests of hypothesized order relations found
      that these behaviors tended to occur in the circular pattern predicted by the IC.
      To illustrate the applicability of the IC to children's behavior, Study 2 (n =
      94) used the circular structure of children's behavior to longitudinally examine
      children's participation in two risk behaviors, smoking cigarettes and consuming
      alcohol. Results indicated that children who behaved in an arrogant-calculating
      manner were at risk for smoking cigarettes and children who behaved in an assured
      dominate manner were at risk for drinking alcohol 1 year later. Implications of
      these results are discussed in terms of their relevance for helping researchers
      better understand and categorize children's interpersonal behaviors.

PMID- 15743989
TI  - Religiousness and the trajectory of self-rated health across adulthood.
AB  - This study evaluates the association of religiousness with the growth parameters
      characterizing changes in self-rated health during adulthood (ages 20-94 years).
      Even after controlling for health behaviors, social support/social activity, and
      four of the Big Five, women who were highly religious in 1940 had higher mean
      self-rated health throughout their lifespan, slower rates of linear decline, and
      less pronounced cascades than did less religious women. For men, the associations
      of religiousness with the growth parameters underlying self-rated health were
      negligible. Results indicate that the association of religiousness with women's
      self-rated health may persist after controlling for mundane mediators and that
      the association of religiousness and self-rated health is not an artifact of the
      association between religiousness and the Big Five.

PMID- 15743990
TI  - Positive affectivity and lifestyle in adulthood: do you do what you feel?
AB  - There is much evidence for the adaptive value of positive affect. Empirical work
      examining different facets of positive affect and their consequences for
      psychological adaptation remains sparse, however. This study (young, middle-aged,
      and older adults; N = 293) investigated the links between two dimensions of
      positive affect (positive involvement and pleasant affect) and two lifestyles
      (hedonic and growth related), each indicated by general value orientations, self
      reported everyday activities, and activity aspirations. Structural equation
      models showed that pleasant affect and positive involvement constitute distinct
      dimensions evincing different age trends and relating differentially to hedonic
      and growth-related lifestyles. Specifically, pleasant affect, but not positive
      involvement, was related to a hedonic lifestyle, whereas positive involvement,
      and not pleasant affect, was associated with a growth-related lifestyle. These
      findings underline the importance of considering two dimensions of positive
      affect--pleasant feelings and positive involvement--separately when studying the
      link between affect and lifestyle.

PMID- 15743992
TI  - Uniform clinical trial registration policy for journals of kidney diseases,
      dialysis, and transplantation.

PMID- 15743993
TI  - Mineralocorticoid versus glucocorticoid receptor occupancy mediating aldosterone
      stimulated sodium transport in a novel renal cell line.
AB  - Aldosterone controls sodium balance by regulating an epithelial sodium channel
      (ENaC)-mediated sodium transport along the aldosterone-sensitive distal nephron,
      which expresses both mineralocorticoid (MR) and glucocorticoid receptors (GR).
      Mineralocorticoid specificity is ensured by 11beta-hydroxysteroid dehydrogenase
      type 2, which metabolizes cortisol or corticosterone into inactive metabolites
      that are unable to bind MR and/or GR. The fractional occupancy of MR and GR by
      aldosterone mediating the sodium transport response in the aldosterone-sensitive
      distal nephron cannot be studied in vivo. For answering this question, a novel
      mouse cortical collecting duct cell line (mCCD(cl1)), which expresses significant
      levels of MR and GR and a robust aldosterone sodium transport response, was used.
      Aldosterone elicited a biphasic response: Low doses (K(1/2) = approximately 0.5
      nM) induced a transient and early increase of sodium transport (peaking at 3 h),
      whereas high doses (K(1/2) = approximately 90 nM) entailed an approximately
      threefold larger, long-lasting response. At 3 h, the corticosterone dose-response
      curve was shifted to the right compared with that of aldosterone by more than two
      log concentrations, an effect that was fully reverted in the presence of the
      11beta-hydroxysteroid dehydrogenase type 2 inhibitor carbenoxolone. Low doses of
      dexamethasone (0.1 to 1 nM) failed to induce an early response, but high doses
      elicited a long-lasting response (K(1/2) = approximately 8 nM), similar to that
      observed for high aldosterone concentrations. Equilibrium binding assays showed
      that both aldosterone and corticosterone bind to a high-affinity, low-capacity
      site, whereas dexamethasone binds to one site. Within the physiologic range of
      aldosterone concentrations, sodium transport is predicted to be controlled by MR
      occupancy during circadian cycles and by MR and GR occupancy during salt
      restriction or acute stress.

PMID- 15743994
TI  - Low turnover osteodystrophy and vascular calcification are amenable to skeletal
      anabolism in an animal model of chronic kidney disease and the metabolic
      syndrome.
AB  - LDL receptor (LDLR)-null mice fed high-fat/cholesterol diets, a model of the
      metabolic syndrome, have vascular calcification (VC) worsened by chronic kidney
      disease (CKD) and ameliorated by bone morphogenetic protein-7 (BMP-7), an
      efficacious agent in treating animal models of renal osteodystrophy. Here, LDLR-/
      high-fat-fed mice without CKD were shown to have significant reductions in bone
      formation rates, associated with increased VC and hyperphosphatemia.
      Superimposing CKD resulted in a low turnover osteodystrophy, whereas VC worsened
      and hyperphosphatemia persisted. BMP-7 treatment corrected the hyperphosphatemia,
      corrected the osteodystrophy, and prevented VC, compatible with skeletal
      phosphate deposition leading to reduced plasma phosphate and removal of a major
      stimulus to VC. A pathologic link between abnormal bone mineralization and VC
      through the serum phosphorus was supported by the partial effectiveness of
      directly reducing the serum phosphate by a phosphate binder that had no skeletal
      action. Thus, in this model of the metabolic syndrome with CKD, a reduction in
      bone-forming potential of osteogenic cells leads to low bone turnover rates,
      producing hyperphosphatemia and VC, processes ameliorated by the skeletal
      anabolic agent BMP-7, in part through deposition of phosphate and increased bone
      formation.

PMID- 15743995
TI  - T-786C polymorphism of the endothelial nitric oxide synthase gene is associated
      with albuminuria in the diabetes heart study.
AB  - Albuminuria demonstrates significant heritability in multiply affected
      hypertensive and diabetic families. The role of endothelial nitric oxide synthase
      (eNOS) gene variants as risk factors for albuminuria was investigated in 590
      European American siblings from 230 families in the Diabetes Heart Study. Two
      polymorphisms in the eNOS gene (T-786C in the promoter region and Glu298Asp in
      exon 7) were genotyped. Albuminuria was defined as an albumin:creatinine ratio
      (ACR) >/=17 mg/g in men and >/=25 mg/g in women. Tests of association were based
      on generalized estimating equations, and tests of linkage disequilibrium were
      based on the quantitative pedigree disequilibrium test. A total of 83% of
      participants had type 2 diabetes. The median ACR was 10.7 mg/g (interquartile
      range, 5.1 to 32.8), and 34% (202 of 590) of participants had an elevated ACR.
      The eNOS -786C allele but not the Glu298Asp was associated with increased ACR
      (31% increase in absolute level of ACR for each additional copy of the -786C
      allele; P < 0.0001) and a higher risk for albuminuria (odds ratio, 1.55 for each
      additional copy of the -786C allele; P = 0.0005). Adjustment for the nongenetic
      determinants of ACR had no significant effect on the results; neither did
      stratification by gender, presence of diabetes, and the Glu298Asp genotype.
      Results were confirmed by quantitative pedigree disequilibrium test analysis and
      were consistent with haplotype analysis. The -786C eNOS variant was positively
      correlated with a higher prevalence and a greater degree of albuminuria in
      European American families in both diabetic and nondiabetic family members.

PMID- 15743996
TI  - Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes.
AB  - Development of microalbuminuria increases the risk for cardiovascular disease
      (CVD) in type 2 diabetes. The nature of this relationship is unclear but may
      involve arterial stiffness, an independent risk marker for CVD mortality. Aortic
      pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in
      134 consecutive patients with type 2 diabetes without overt renal impairment
      (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients
      with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and
      higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with
      normal ACR. The closest univariate associations of Ao-PWV were positively with
      age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively
      with GFR and weight (all P < 0.01). In a multiple linear step-down regression
      analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of
      diabetes, gender, number of antihypertensive medications, and use of angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers, which together
      explained 55% of the variance of Ao-PWV. When ACR was offered in place of
      arterial pressure to a separate model, ACR emerged as a significant predictor of
      Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao
      PWV than those with GFR above the median (P = 0.043). In patients with type 2
      diabetes without overt renal impairment, raised ACR is associated with higher Ao
      PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV
      with reduced GFR suggests that even modest renal dysfunction may affect the
      viscoelastic properties of large arteries.

PMID- 15743997
TI  - High prevalence of occult coronary artery stenosis in patients with chronic
      kidney disease at the initiation of renal replacement therapy: an angiographic
      examination.
AB  - The prevalence of coronary artery stenosis (CAS) at the initiation of renal
      replacement therapy (RRT) in patients with chronic kidney disease (CKD) and no
      previous history of angina and/or myocardial infarction (MI) has not been fully
      elucidated. The prevalence of significant CAS was evaluated in 30 asymptomatic
      stage 5 CKD patients without a history of angina and/or MI by coronary
      angiography at the initiation of RRT. The correlations of various parameters with
      the prevalence of CAS were also examined. Atherosclerotic surrogate markers,
      including intima-media thickness of carotid artery and ankle-brachial BP index
      (ABI), were also evaluated. Significant CAS (>50% stenosis) was seen in 16
      (53.3%) of 30 asymptomatic CKD patients on coronary angiography at the start of
      RRT. Stress cardiac scintigraphy was not effective for detecting hidden cardiac
      ischemia among the CKD patients. Univariate analysis showed that diabetes (P =
      0.01), left ventricular mass index (P = 0.04), hyperlipidemia (P = 0.04), total
      cholesterol (P = 0.02), LDL cholesterol (P < 0.01), intima-media thickness (P =
      0.04), and fibrinogen (P = 0.01) were positively correlated with the presence of
      CAS, whereas ABI (P < 0.01) showed a negative correlation with CAS. Stepwise
      logistic regression analysis revealed that diabetes and fibrinogen were
      significant and independent risk factors for CAS in asymptomatic CKD patients who
      started RRT. The results clearly demonstrated that despite the absence of cardiac
      events, stage 5 CKD patients are already in a very high risk group for CAS at the
      initiation of RRT, which was also closely associated with a significant decrease
      in ABI.

PMID- 15743998
TI  - Renal insulin resistance syndrome, adiponectin and cardiovascular events in
      patients with kidney disease: the mild and moderate kidney disease study.
AB  - The relationship among insulin resistance, adiponectin, and cardiovascular (CV)
      morbidity in patients with mild and moderate kidney disease was investigated.
      Insulin sensitivity (Homeostasis Model Assessment of Insulin Resistance [HOMA
      IR]) and adiponectin plasma levels were assessed in 227 nondiabetic renal
      patients at different degrees of renal dysfunction and in 76 healthy subjects of
      similar age and gender distribution and body mass index. In renal patients,
      association with prevalent CV events was evaluated, and incident CV events were
      evaluated in a prospective study. HOMA-IR was markedly higher in patients than in
      healthy subjects (3.59 +/- 3.55 versus 1.39 +/- 0.51; P < 0.01). In renal
      patients, HOMA-IR was significantly correlated with body mass index (r = 0.477; P
      < 0.01), triglycerides (r = 0.384; P < 0.01), adiponectin plasma levels (r = 
      0.253; P < 0.01), and age (r = 0.164; P < 0.05), but not with renal function (GFR
      by iod-thalamate clearance). Patients with previous CV events were significantly
      older, had higher HOMA-IR and serum triglycerides, and had lower adiponectin
      plasma levels (all P < 0.05). Logistic regression analysis revealed age (P <
      0.001) and adiponectin (P < 0.002) as independent variables related to prevalent
      CV events. In the prospective study, median follow-up was 54 mo. Patients who
      experienced CV events had significantly higher serum glucose and lower
      adiponectin plasma levels (both P < 0.05). In patients with chronic kidney
      diseases, a syndrome of insulin resistance is present even in the earliest stage
      of renal dysfunction, and several components of this syndrome are associated with
      CV events. Moreover, hypoadiponectinemia is a novel putative CV risk factor in
      patients with mild and moderate renal failure.

PMID- 15743999
TI  - Vasodilator-stimulated phosphoprotein-deficient mice demonstrate increased
      platelet activation but improved renal endothelial preservation and regeneration
      in passive nephrotoxic nephritis.
AB  - Vasodilator-stimulated phosphoprotein (VASP), an actin cytoskeletal protein, is
      expressed in various cell types including renal cells. In vitro studies provide
      evidence for a role of VASP regarding platelet activation, cell adhesion,
      migration, and capillary formation. The in vivo role of VASP was investigated in
      experimental inflammatory renal disease. Kidneys of healthy VASP deficient (-/-)
      and wild-type (wt) mice were compared regarding morphology and functional
      parameters. Passive nephrotoxic nephritis was induced in 28 VASP -/- and 28 wt
      mice; kidneys were harvested; and tissues were analyzed by morphometric,
      immunohistochemical, and electron microscopic techniques on days 3, 7, 14, and
      28. The time course of disease in VASP -/- mice differed substantially and
      biphasically from that in wt controls. Early on, VASP -/- mice demonstrated
      increased platelet influx associated with augmented glomerular and
      tubulointerstitial inflammation and sclerosis. Whereas renal disease continuously
      worsened up to day 28 in wt controls, renal disease in VASP -/- mice hardly
      progressed after day 3 as assessed by various injury indices. This long-term
      improvement of renal histology in VASP -/- compared with wt mice was associated
      with remarkable capillary preservation/regeneration up to day 28 mediated via an
      increased proliferative and a reduced apoptotic activity of VASP-negative
      peritubular endothelial cells. Despite an enhanced injury response early on, VASP
      -/- mice are protected from long-term progression of nephrotoxic nephritis, which
      is associated with improved renal endothelial cell preservation and regeneration.

PMID- 15744001
TI  - Intrarenal injection of bone marrow-derived angiogenic cells reduces endothelial
      injury and mesangial cell activation in experimental glomerulonephritis.
AB  - Loss of glomerular endothelial cells has been suggested to contribute to the
      progression of glomerular injury. Although therapeutic angiogenesis induced by
      administration of bone marrow-derived endothelial progenitor cells has been
      observed in disease models of endothelial injury, the effects on renal disease
      have not been clarified. Whether administration of culture-modified bone marrow
      mononuclear cells would mitigate the glomerular endothelial injury in anti-Thy1.1
      nephritis was investigated. After cultivation under conditions that promote
      endothelial progenitor cell growth, bone marrow mononuclear cells were labeled
      with CM-DiI, a fluorescence marker, and injected into the left renal artery of
      Lewis rats with anti-Thy1.1 glomerulonephritis. The decrease in glomerular
      endothelial cells was significantly attenuated in the left kidney, as compared
      with the right, in nephritic rats that received the cell infusion. Glomerular
      injury score, the area positive for mesangial alpha-smooth muscle actin, and
      infiltration of macrophages were significantly decreased in the left kidney. CM
      DiI-positive cells were distributed in glomeruli of the left kidney but not in
      those of the right kidney. Among CM-DiI-labeled cells incorporated into
      glomeruli, 16.5 +/- 1.2% of cells were stained with an endothelial marker, rat
      endothelial cell antigen-1. Culture-modified mononuclear cells secreted 281.2 +/-
      85.0 pg of vascular endothelial growth factor per 10(5) cells per day. In
      conclusion, intra-arterial administration of culture-modified bone marrow
      mononuclear cells reduced endothelial injury and mesangial activation in anti
      Thy1.1 glomerulonephritis. Incorporation into the glomerular endothelial lining
      and production of angiogenic factor(s) are likely to contribute to the protective
      effects of culture-modified mononuclear cells against glomerular injury.

PMID- 15744000
TI  - Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell
      carcinoma.
AB  - Human kidney injury molecule-1 (hKIM-1) is a type 1 transmembrane protein that is
      not detectable in normal kidney tissue but is expressed at high levels in human
      and rodent kidneys with dedifferentiated proximal tubule epithelial cells after
      ischemic or toxic injury. Therefore, it was hypothesized that renal tumors
      express hKIM-1 and release this protein into the urine. Forty renal cell
      carcinoma (RCC) and 484 nonrenal tumors were analyzed by immunohistochemistry for
      expression of hKIM-1 (group 1). Urine samples before nephrectomy and nephrectomy
      tissue samples were collected from an additional 42 patients with renal tumors,
      from 30 normal control subjects, and also from 10 patients with prostate
      carcinoma (group 2). In five additional patients with RCC, urine was collected
      before and after nephrectomy (group 3). Tissue was examined for expression of
      hKIM-1, and cell-free urine supernatants were analyzed for hKIM-1 by ELISA.
      Urinary hKIM-1 was normalized to the urinary creatinine concentration (U(Cr)).
      Expression of hKIM-1 was present in 32 tissue sections (91%) of 35 clear cell RCC
      (group 1). In group 2, the normalized urinary hKIM-1 levels were significantly
      higher in patients with clear cell RCC (0.39 +/- 0.08 ng/mg U(Cr); n = 21),
      compared with levels in patients with prostate carcinoma (0.12 +/- 0.03 ng/mg
      U(Cr); P < 0.02; n = 10), or normal control subjects (0.05 +/- 0.01 ng/mg U(Cr);
      P < 0.005; n = 30). Tissue sections from 28 (82%) of 34 primary RCC stained
      positively for the expression of hKIM-1. In all patients with a detectable
      prenephrectomy urinary hKIM-1 level, there was either complete disappearance or
      marked reduction after nephrectomy (group 3). In conclusion, the cleaved
      ectodomain of hKIM-1 can be detected in the urine of patients with RCC and may
      serve as a new biomarker for early detection of RCC.

PMID- 15744002
TI  - Effect of chymase inhibition on the arteriovenous fistula stenosis in dogs.
AB  - It was hypothesized that chymase may participate in hemodialysis vascular access
      dysfunction, as chymase has been known to be an effective enzyme in the
      conversion of angiotensin I (Ang I) to Ang II and in the latent TGF-beta1 to the
      active form. An arteriovenous (AV) fistula was created between the brachial
      artery and vein in dogs. In the AV anastomosis, when the walls of the venous and
      arterial sides were compared, the eccentric neointimal formation was most evident
      in the venous wall. Compared with the venous side downstream of the AV
      anastomosis, a severe neointimal hyperplasia was found in the venous side
      upstream of the AV anastomosis (intima/media, 153 +/- 25%). The chymase- and TGF
      beta-positive mast cells were markedly accumulated in the proliferous neointima
      and media. In association with the reduction of chymase expression, a marked
      decrease in Ang II-, AT(1) receptor-, and TGF-beta-positive areas was achieved by
      NK3201 (a chymase inhibitor) treatment, and the neointima formation
      (intima/media: region A, 53 +/- 9%, P < 0.001; region B, 54 +/- 14%, P < 0.001)
      was also significantly suppressed in this group. Although lisinopril treatment
      also provided some beneficial effects with regard to the prevention of neointimal
      formation, the degree was less than that seen with chymase inhibition. These
      findings indicate that mast cell-derived chymase plays an essential role in the
      pathogenesis of the AV fistula access failure and that chymase inhibition may be
      a therapeutic target for the treatment of hemodialysis vascular access
      dysfunction in clinic settings.

PMID- 15744003
TI  - Rat nucleus accumbens neurons predominantly respond to the outcome-related
      properties of conditioned stimuli rather than their behavioral-switching
      properties.
AB  - It has been proposed that nucleus accumbens neurons respond to outcome (reward
      and punishment) and outcome-predictive information. Alternatively, it has been
      suggested that these neurons respond to salient stimuli, regardless of their
      outcome-predictive properties, to facilitate a switch in ongoing behavior. We
      recorded the activity of 82 single-nucleus accumbens neurons in thirsty rats
      responding within a modified go/no-go task. The task design allowed us to analyze
      whether neurons responded to conditioned stimuli that predicted rewarding
      (saccharin) or aversive (quinine) outcomes, and whether the neural responses
      correlated with behavioral switching. Approximately one third (28/82) of nucleus
      accumbens neurons exhibited 35 responses to conditioned stimuli. Over 2/3 of
      these responses encoded the nature of the upcoming rewarding (19/35) or aversive
      (5/35) outcome. No response was selective solely for the switching of the rat's
      behavior, although the activity of approximately one third of responses (11/35)
      predicted the upcoming outcome and was correlated with the presence or absence of
      a subsequent behavioral switch. Our data suggest a primary functional role for
      the nucleus accumbens in encoding outcome-predicting information and a more
      limited role in behavioral switching.

PMID- 15744004
TI  - Synchronization of motor units in human soleus muscle during standing postural
      tasks.
AB  - During standing posture, the soleus muscles acts to control sway in the
      anteroposterior (AP) direction. The soleus muscles bilaterally share a common
      function during standing tasks. We sought to determine whether common descending
      inputs, as evidenced by the synchronization of bilateral motor unit pairs, were
      employed as a strategy to control this common function. Single motor units were
      recorded from the soleus muscles in subjects who stood on adjacent force
      platforms for 5 min with their eyes open or closed. While standing with the eyes
      open, only 4/39 bilateral motor unit pairs showed significant synchronization.
      Similarly, only 3/36 motor unit pairs were significantly synchronized during the
      eyes closed task. The low incidence of synchronization was observed despite a
      high correlation in the amount of sway in the AP direction between legs in both
      the eyes open and eyes closed tasks (rho = 0.80 and rho = 0.83, respectively).
      When the extent of synchronization was assessed between pairs of motor units
      within the same leg with the eyes open, 10/12 pairs were synchronized.
      Furthermore, when pairs of soleus motor units were recorded both bilaterally and
      unilaterally during voluntary isometric ankle plantarflexion, only 4/30 bilateral
      pairs showed significant synchronization, whereas 19/24 unilateral pairs had
      significant synchronization. In this study, there was little evidence of the
      existence of synchronization between bilateral soleus motor unit pairs in either
      postural tasks or voluntary isometric contractions. In cases in which bilateral
      synchronization was observed, it was considerably weaker than the synchronization
      of motor units within a single soleus muscle. The results of this study reveal
      that it is rather uncommon for bilateral soleus motoneurons to receive common
      descending synaptic inputs, whereas two motoneurons within a single soleus muscle
      do.

PMID- 15744005
TI  - Coherence at 16-32 Hz can be caused by short-term synchrony of motor units.
AB  - Time- and frequency-domain measures of discharge times for pairs of motor units
      are used to infer the proportion of common synaptic input received by motor
      neurons. The physiological mechanisms that can produce the experimentally
      observed peaks in the cross-correlation histogram and the coherence spectrum are
      uncertain. The present study used a computational model to impose synchronization
      on the discharge times of motor units. Randomly selected discharge times of a
      unit that was being synchronized to a reference unit were aligned with some of
      the discharge times of the reference unit, provided the original discharge time
      was within 30 ms of the discharge by the reference unit. All time-domain measures
      (indexes CIS, E, and k') were sensitive to changes in the level of imposed motor
      unit synchronization (P < 0.01). In addition, synchronization caused a peak
      between 16 and 32 Hz in the coherence spectrum. The shape of the cross
      correlogram determined the frequency at which the peak occurred in the coherence
      spectrum. Further, the magnitude of the coherence peak was highly correlated with
      the time-domain measures of motor-unit synchronization (r2 > 0.80), with the
      highest correlation occurring for index E (r2 = 0.98). Thus the peak in the 16-
      to 32-Hz band of the coherence spectrum can be caused by the time that individual
      discharges are advanced or delayed to produce synchrony. Although the in vivo
      processes that adjust the timing of motor-unit discharges are not fully
      understood, these results suggest that they may not depend entirely on an
      oscillatory drive by the CNS.

PMID- 15744006
TI  - Periodic modulation of motor-unit activity in extrinsic hand muscles during
      multidigit grasping.
AB  - We recently examined the extent to which motor units of digit flexor muscles
      receive common input during multidigit grasping. This task elicited moderate to
      strong motor-unit synchrony (common input strength, CIS) across muscles (flexor
      digitorum profundus, FDP, and flexor pollicis longus, FPL) and across FDP muscle
      compartments, although the strength of this common input was not uniform across
      digit pairs. To further characterize the neural mechanisms underlying the control
      of multidigit grasping, we analyzed the relationship between firing of single
      motor units from these hand muscles in the frequency domain by computing
      coherence. We report three primary findings. First, in contrast to what has been
      reported in intrinsic hand muscles, motor units belonging to different muscles
      and muscle compartments of extrinsic digit flexors exhibited significant
      coherence in the 0- to 5- and 5- to 10-Hz frequency ranges and much weaker
      coherence in the higher 10-20 Hz range (maximum 0.0025 and 0.0008, respectively,
      pooled across all FDP compartment pairs). Second, the strength and incidence of
      coherence differed considerably across digit pairs. Third, contrary to what has
      been reported in the literature, across-muscle coherence can be stronger and more
      prevalent than within-muscle coherence, as FPL-FDP2 (thumb-index digit pair)
      exhibited the strongest and most prevalent coherence in our data (0.010 and 43%
      at 3 Hz, respectively). The heterogeneous organization of common input to these
      muscles and muscle compartments is discussed in relation to the functional role
      of individual digit pairs in the coordination of multiple digit forces in
      grasping.

PMID- 15744007
TI  - Effects of inhibitory feedback in a network model of avian brain stem.
AB  - The avian auditory brain stem consists of a network of specialized nuclei,
      including nucleus laminaris (NL) and superior olivary nucleus (SON). NL cells
      show sensitivity to interaural time difference (ITD), a critical cue that
      underlies spatial hearing. SON cells provide inhibitory feedback to the rest of
      the network. Empirical data suggest that feedback inhibition from SON could
      increase the ITD sensitivity of NL across sound level. Using a bilateral network
      model, we assess the effects of SON feedback inhibition. Individual cells are
      specified as modified leaky-integrate-and-fire neurons with time constants and
      thresholds that vary with inhibitory input. Acoustic sound level is reflected in
      the discharge rates of the model auditory-nerve fibers, which innervate the
      network. Simulations show that with SON inhibitory feedback, ITD sensitivity is
      maintained in model NL cells over a threefold range in auditory-nerve discharge
      rate. In contrast, without SON feedback inhibition, ITD sensitivity is
      significantly reduced as input rates are increased. Feedback inhibition is most
      beneficial in maintaining ITD sensitivity at high-input rates (simulating high
      sound levels). With SON inhibition, ITD sensitivity is maintained for both
      interaurally balanced inputs (simulating an on-center sound source) and
      interaurally imbalanced inputs (simulating a lateralized source). Further, the
      empirically observed temporal build-up of SON inhibition and the presence of
      reciprocal inhibitory connections between the ipsi- and contralateral SON both
      improve ITD sensitivity. In sum, our network model shows that inhibitory feedback
      can substantially increase the sensitivity and dynamic range of ITD coding in the
      avian auditory brain stem.

PMID- 15744008
TI  - Frontoparietal control of spatial attention and motor intention in human EEG.
AB  - Relations between spatial attention and motor intention were investigated by
      means of an EEG potential elicited by shifting attention to a location in space
      as well as by the selection of a hand for responding. High-density recordings
      traced this potential to a common frontoparietal network activated by attentional
      orienting and by response selection. Within this network, parietal and frontal
      cortex were activated sequentially, followed by an anterior-to-posterior
      migration of activity culminating in the lateral occipital cortex. Based on
      temporal and polarity information provided by EEG, we hypothesize that the
      frontoparietal activation, evoked by directional information, updates a task
      defined preparatory state by deselecting or inhibiting the behavioral option
      competing with the cued response side or the cued direction of attention. These
      results from human EEG demonstrate a direct EEG manifestation of the
      frontoparietal attention network previously identified in functional imaging. EEG
      reveals the time-course of activation within this network and elucidates the
      generation and function of associated directing-attention EEG potentials. The
      results emphasize transient activation and a decision-related function of the
      frontoparietal attention network, contrasting with the sustained preparatory
      activation that is commonly inferred from neuroimaging.

PMID- 15744009
TI  - Optically recorded response of the superficial dorsal horn: dissociation from
      neuronal activity, sensitivity to formalin-evoked skin nociceptor activation.
AB  - In rat spinal cord, slice repetitive electrical stimulation of the dorsal root at
      an intensity that activates C-fibers evokes a slow-to-develop and prolonged (30
      50 s) change in light transmittance (OIS(DR)) in the superficial part of the
      ipsilateral dorsal horn (DH(s)). Inhibition of astrocyte metabolism [by bath
      applied 400 microM fluoroacetate and 200 microM glutamine (FAc + Gln)] or
      interference with glial and neuronal K+ transport [by 100 microM 4-aminopyridine
      (4-AP)] leads to dissociation of the OIS(DR) and the postsynaptic DH(s) response
      to a single-pulse, constant-current dorsal root stimulus (P-PSP(DR)). The OIS(DR)
      decreases under FAc+Gln, whereas the P-PSP(DR) remains unaltered; under 4-AP, the
      P-PSP(DR) increases, but the OIS(DR) decreases. In contrast, both the OIS(DR) and
      P-PSP(DR) increase when K(+)o is elevated to 8 mM. These observations from slices
      from normal subjects are interpreted to indicate that the OIS(DR) mainly reflects
      cell volume and light scattering changes associated with DH(s) astrocyte uptake
      of K+ and glutamate (GLU). In slices from subjects that received an
      intracutaneous injection of formalin 3-5 days earlier, both the OIS(DR) and the
      response of the DH(s) ipsilateral to the injection site to 100-ms local
      application (via puffer pipette) of 15 mM K+ or 100 microM GLU were profoundly
      reduced, and the normally exquisite sensitivity of the DH(s) to elevated K(+)o is
      decreased. Considered collectively, the observations raise the possibility that
      impaired regulation of DH(s) K(+)o and GLU(o) may contribute to initiation and
      maintenance of the CNS pain circuit and sensorimotor abnormalities that develop
      following intracutaneous formalin injection.

PMID- 15744010
TI  - Glycine binding site of the synaptic NMDA receptor in subpostremal NTS neurons.
AB  - The nucleus of the tractus solitarius (NTS) plays an important role in the
      control of several autonomic reflex functions and has glutamate and GABA as main
      neurotransmitters. In this work, we used patch-clamp recordings in transverse
      slice preparations from rats to study whether the glycine binding site of the N
      methyl-D-aspartate (NMDA) receptor is saturated or not in neurons of the
      subpostremal NTS. Except at hyperpolarized voltages and close to the reversal
      potential, glycine potentiated the NMDA responses in a concentration-dependent
      manner. The total charge transferred by glutamatergic currents was enhanced by
      glycine (500 microM; from 28 +/- 13 to 42 +/- 18 pC at +50 mV, n = 7, P < 0.05).
      Glycine increased the conductance of the postsynaptic membrane, without altering
      its reversal potential, both in the presence (from 2.4 +/- 0.06 to 3.4 +/- 0.09
      nS; n = 7) and absence (from 3.1 +/- 0.06 to 4.4 +/- 0.10 nS; n = 8) of Mg2+ in
      the bathing solution. d-serine, in the presence of strychnine, also increased the
      amplitude of the NMDA component (by 68 +/- 19%, P < 0.05, n = 5). The membrane
      potential was hyperpolarized (16 +/- 6 mV, n = 8) by glycine, suggesting the
      presence of inhibitory glycinergic receptors. Our results indicate that the
      glycine site of the NMDA receptor in neurons of the subpostremal NTS is not
      saturated and that glycine may act as a modulator of the NMDA transmission in
      this nucleus.

PMID- 15744011
TI  - Temporal properties of inputs to direction-selective neurons in monkey V1.
AB  - Motion in the visual scene is processed by direction-selective neurons in primary
      visual cortex. These cells receive inputs that differ in space and time. What are
      these inputs? A previous single-unit recording study in anesthetized monkey V1
      proposed that the two major streams arising in the primate retina, the M and P
      pathways, differed in space and time as required to create direction selectivity.
      We confirmed that cortical cells driven by P inputs tend to have sustained
      responses. The M pathway, however, as assessed by recordings in layer 4Calpha and
      from cells with high contrast sensitivity, is not purely transient. The diversity
      of timing in the M stream suggests that combinations of M inputs, as well as of M
      and P inputs, create direction selectivity.

PMID- 15744012
TI  - Application of nucleus pulposus to L5 dorsal root ganglion in rats enhances
      nociceptive dorsal horn neuronal windup.
AB  - Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly
      results in radiculopathic pain possibly through a neuroinflammatory response. NP
      sensitizes dorsal horn neuronal responses, but it is unknown whether this
      reflects a central or peripheral sensitization. To study central sensitization,
      we tested if NP enhances windup--the progressive increase in the response of a
      nociceptive spinal neuron to repeated electrical C-fiber stimulation--a
      phenomenon that may partly account for temporal summation of pain. Single-unit
      recordings were made from wide dynamic range (WDR; n = 36) or nociceptive
      specific (NS; n = 8) L5 dorsal horn neurons in 44 isoflurane-anesthetized rats.
      Subcutaneous electrodes delivered electrical stimuli (20 pulses, 3 times the C
      fiber threshold, 0.5 ms) to the receptive field on the hindpaw. Autologous NP was
      harvested from a tail disc and placed onto the L5 dorsal root ganglion after
      recording of baseline responses (n = 22). Controls had saline applied similarly
      (n = 22). Electrical stimulus trains (0.1, 0.3, and 1 Hz; 5-min interstimulus
      interval) were repeated every 30 min for 3-6 h after each treatment. The total
      number of evoked spikes (summed across all 20 stimuli) to 0.1 Hz was enhanced 3 h
      after NP, mainly in the after-discharge (AD) period (latency > 400 ms). Total
      responses to 0.3 and 1.0 Hz were also enhanced at > or = 60 min after NP in both
      the C-fiber (100- to 400-ms latency) and AD periods, whereas the absolute windup
      (C-fiber + AD - 20 times the initial response) increased at > or = 90 min after
      treatment. In saline controls, windup was not enhanced at any time after
      treatment for any stimulus frequency, although there was a trend toward
      enhancement at 0.3 Hz. These results are consistent with NP-induced central
      sensitization. Mechanical responses were not significantly enhanced after saline
      or NP treatment. We speculate that inflammatory agents released from (or
      recruited by) NP affect the dorsal root ganglion (and/or are transported to cord)
      to enhance primary afferent excitation of nociceptive dorsal horn neurons.

PMID- 15744014
TI  - Contextual masking of oriented lines: interactions between surface segmentation
      cues.
AB  - The ability of human observers to detect and discriminate a single feature of a
      visual image deteriorates markedly when the targeted feature is surrounded by
      others of a similar kind. This perceptual masking is mirrored by the suppressive
      effects of surround stimulation on the responses of neurons in primary visual
      cortex (area V1). Both perceptual and neuronal masking effects are partially
      relieved, however, if the targeted image feature is distinguished from
      surrounding features along some dimension, such as contour orientation. Masking
      relief is likely to play an important role in perceptual segmentation of complex
      images. Because dissimilar surfaces usually differ along multiple feature
      dimensions, we tested the possibility that those differences may influence
      segmentation in an invariant manner. As expected, we found that the presence of
      surrounding features resulted in perceptual masking and neuronal response
      suppression in area V1, but that either orientation or contrast polarity
      differences between the target and surrounding features was sufficient to
      partially relieve these effects. Simultaneous differences along both dimensions,
      however, yielded no greater relief from masking than did either difference alone.
      Although the averaged neuronal effects of orientation polarity cues were thus
      invariant, the time course over which these effects emerged after each stimulus
      appearance was different for the two cues. These findings refine our
      understanding of the functions of nonclassical receptive fields, and they support
      a key role for V1 neurons in surface segmentation.

PMID- 15744013
TI  - Membrane potential oscillations in reticulospinal and spinobulbar neurons during
      locomotor activity.
AB  - Feedback from the spinal locomotor networks provides rhythmic modulation of the
      membrane potential of reticulospinal (RS) neurons during locomotor activity. To
      further understand the origins of this rhythmic activity, the timings of the
      oscillations in spinobulbar (SB) neurons of the spinal cord and in RS neurons of
      the posterior and middle rhombencephalic reticular nuclei were measured using
      intracellular microelectrode recordings in the isolated brain stem-spinal cord
      preparation of the lamprey. A diffusion barrier constructed just caudal to the
      obex allowed induction of locomotor activity in the spinal cord by bath
      application of an excitatory amino acid to the spinal bath. All of the
      ipsilaterally projecting SB neurons recorded had oscillatory membrane potentials
      with peak depolarizations in phase with the ipsilateral ventral root bursts,
      whereas the contralaterally projecting SB neurons were about evenly divided
      between those in phase with the ipsilateral ventral root bursts and those in
      phase with the contralateral bursts. In the brain stem under these conditions,
      75% of RS neurons had peak depolarizations in phase with the ipsilateral ventral
      root bursts while the remainder had peak depolarizations during the contralateral
      bursts. Addition of a high-Ca2+, Mg2+ solution to the brain stem bath to reduce
      polysynaptic activity had little or no effect on oscillation timing in RS
      neurons, suggesting that direct inputs from SB neurons make a major contribution
      to RS neuron oscillations under these conditions. Under normal conditions when
      the brain is participating in the generation of locomotor activity, these spinal
      inputs will be integrated with other inputs to RS neurons.

PMID- 15744015
TI  - Selenoprotein P is required for mouse sperm development.
AB  - Selenoprotein P (SEPP1), an extracellular glycoprotein of unknown function, is a
      unique member of the selenoprotein family that, depending on species, contains 10
      17 selenocysteines in its primary structure; in contrast, all other family
      members contain a single selenocysteine residue. The SEPP1-null (Sepp1(-/-)) male
      but not the female mice are infertile, but the cellular basis of this male
      phenotype has not been defined. In this study, we demonstrate that mature
      spermatozoa of Sepp1(-/-) males display a specific set of flagellar structural
      defects that develop temporally during spermiogenesis and after testicular
      maturation in the epididymis. The flagellar defects include a development of a
      truncated mitochondrial sheath, an extrusion of a specific set of axonemal
      microtubules and outer dense fibers from the principal piece, and ultimately a
      hairpin-like bend formation at the midpiece-principal piece junction. The sperm
      defects found in Sepp1(-/-) males appear to be the same as those observed in wild
      type (Sepp1(+/+)) males fed a low selenium diet. Supplementation of dietary
      selenium levels for Sepp1(-/-) males neither reverses the development of sperm
      defects nor restores fertility. These data demonstrate that SEPP1 is required for
      development of functional spermatozoa and indicate that it is an essential
      component of the selenium delivery pathway for developing germ cells.

PMID- 15744016
TI  - Neuroendocrine consequences of prenatal androgen exposure in the female rat:
      absence of luteinizing hormone surges, suppression of progesterone receptor gene
      expression, and acceleration of the gonadotropin-releasing hormone pulse
      generator.
AB  - Preovulatory GnRH and LH surges depend on activation of estrogen (E2)-inducible
      progesterone receptors (PGRs) in the preoptic area (POA). Surges do not occur in
      males, or in perinatally androgenized females. We sought to determine whether
      prenatal androgen exposure suppresses basal or E2-induced Pgr mRNA expression or
      E2-induced LH surges (or both) in adulthood, and whether any such effects may be
      mediated by androgen receptor activation. We also assessed whether prenatal
      androgens alter subsequent GnRH pulsatility. Pregnant rats received testosterone
      or vehicle daily on Embryonic Days 16-19. POA-hypothalamic tissues were obtained
      in adulthood for PgrA and PgrB (PgrA+B) mRNA analysis. Females that had prenatal
      exposure to testosterone (pT) displayed reduced PgrA+B mRNA levels (P < 0.01)
      compared with those that had prenatal exposure to vehicle (pV). Additional
      pregnant animals were treated with vehicle or testosterone, or with 5alpha
      dihydrotestosterone (DHT). In adult ovariectomized offspring, estradiol benzoate
      produced a 2-fold increase (P < 0.05) in PgrA+B expression in the POA of pV
      females, but not in pT females or those that had prenatal exposure to DHT (pDHT).
      Prenatal testosterone and DHT exposure also prevented estradiol benzoate-induced
      LH surges observed in pV rats. Blood sampling of ovariectomized rats revealed
      increased LH pulse frequency in pDHT versus pV females (P < 0.05). Our findings
      support the hypothesis that prenatal androgen receptor activation can contribute
      to the permanent defeminization of the GnRH neurosecretory system, rendering it
      incapable of initiating GnRH surges, while accelerating basal GnRH pulse
      generator activity in adulthood. We propose that the effects of prenatal androgen
      receptor activation on GnRH neurosecretion are mediated in part via permanent
      impairment of E2-induced PgrA+B gene expression in the POA.

PMID- 15744017
TI  - Bovine model for the study of reproductive aging in women: follicular, luteal,
      and endocrine characteristics.
AB  - At present, there is no well-characterized animal model to study the effects of
      aging on fertility in women. The objectives of the study were to characterize age
      related changes in ovarian and endocrine functions in old cows and to investigate
      the validity of a bovine model for the study of human reproductive aging. We
      tested the hypotheses that aging in cattle is associated with 1) elevated
      concentrations of gonadotropins and reduced concentrations of steroid hormones in
      systemic circulation and 2) increased recruitment of ovarian follicles during
      wave emergence. Daily ultrasonography was performed in 13- to 14-yr-old cows (n =
      10) and their 1- to 4-yr-old daughters (n = 9) for one interovulatory interval to
      study ovarian function. Plasma samples were obtained every 12 h for determination
      of FSH, LH, progesterone, and estradiol concentrations. Circulating FSH
      concentrations were higher (P = 0.009) during follicular waves in old cows than
      in their daughters, but the number of 4- to 5-mm follicles recruited into a wave
      was lower (P = 0.04) in old cows. Plasma LH concentrations did not differ between
      groups (P = 0.4), but the ovulatory follicle in two-wave cycles was smaller in
      old cows (P = 0.04). Plasma estradiol concentrations were higher (P = 0.01) in
      old cows, and luteal phase progesterone tended to be lower (P = 0.1). We conclude
      that these changes are consistent with those reported for women approaching
      menopause transition. Therefore, our results validate the use of the bovine model
      to study reproductive aging in women.

PMID- 15744018
TI  - The effect of the manipulation of follicle-stimulating hormone (FSH)-peak
      characteristics on follicular wave dynamics in sheep: does an ovarian-independent
      endogenous rhythm in FSH secretion exist?
AB  - We designed three experiments to investigate the relationship between FSH peaks
      and ovarian follicular waves and to examine whether an endogenous rhythm of FSH
      peaks exists in sheep. In experiment 1, anestrous ewes were treated with ovine
      FSH (oFSH) or vehicle (6 ewes per group) at the expected time of an endogenous
      FSH peak, to double the FSH-peak amplitude in treated ewes. In experiment 2,
      anestrous ewes were treated with either oFSH or vehicle (6 ewes per group) at the
      expected time of two consecutive interpeak nadirs, such that the treated ewes had
      5 FSH peaks in the time frame of 3 FSH peaks in control ewes. In experiment 3, to
      measure FSH concentrations, daily blood samples were collected from 5 cyclic ewes
      for a control period during the estrous cycle and then for three 17-day periods
      after ovariectomy. Daily blood samples were collected from another group of 8
      ovariectomized ewes that were treated with estradiol-releasing implants and
      intravaginal progestogen sponges. Doubling the FSH-peak amplitude did not alter
      the characteristics of the following follicular wave. Increasing the frequency of
      FSH peaks stimulated the emergence of additional follicular waves, but did not
      alter the rhythmic occurrence of FSH peaks and follicular wave emergence.
      Endogenous follicular waves in oFSH-treated ewes emerged and grew in the presence
      of the growing largest follicle of the induced follicular waves. Finally, based
      on the observation of serum FSH concentrations in ovariectomized ewes, it appears
      that there exists an endogenous rhythm for peaks in daily serum FSH
      concentrations, which is, at least in part, independent of regulation by ovarian
      follicular growth patterns.

PMID- 15744019
TI  - Expression of the reproductive female-specific vitellogenin gene in
      endocrinologically induced male and intersex Cherax quadricarinatus crayfish.
AB  - In oviparous females, the synthesis of the yolk precursor vitellogenin is an
      important step in ovarian maturation and oocyte development. In decapod
      Crustacea, including the red-claw crayfish (Cherax quadricarinatus), this
      reproductive process is regulated by inhibitory neurohormones secreted by the
      endocrine X-organ-sinus gland (XO-SG) complex. In males, the C. quadricarinatus
      vitellogenin gene (CqVg), although present, is not expressed under normal
      conditions. We show here that endocrine manipulation by removal of the XO-SG
      complex from male animals induced CqVg transcription. The CqVg gene was expressed
      differentially during the molt cycle in these induced males: no expression was
      seen in the intermolt stages, but expression was occasionally detected in the
      premolt stages and always detected in the early postmolt stages. Relative
      quantitation with a real-time reverse transcriptase-polymerase chain reaction
      showed that expression of CqVg in induced early postmolt males was an order of
      magnitude lower than that in reproductive females, a finding that was consistent
      with RNA in situ hybridization results. The SDS-PAGE of high-density lipoproteins
      from the hemolymph of endocrinologically induced early postmolt males did not
      show the typical vitellogenin-related polypeptide profile found in reproductive
      females. On the other hand, removal of the XO-SG complex from intersex
      individuals, which are chromosomally female but functionally male and possess an
      arrested female reproductive system, induced the expression, translation, and
      release of CqVg products into the hemolymph, as was the case for vitellogenic
      females. The expression of CqVg in endocrinologically manipulated molting males
      and intersex animals provides an inducible model for the investigation and
      understanding of the endocrine regulation of CqVg expression and translation in
      Crustacea as well as the relationship between the endocrine axes regulating molt
      and reproduction.

PMID- 15744020
TI  - Fertilization and inositol 1,4,5-trisphosphate (IP3)-induced calcium release in
      type-1 inositol 1,4,5-trisphosphate receptor down-regulated bovine eggs.
AB  - It is widely believed that stimulation of the phosphoinositide pathway and
      production of 1,4,5-inositol trisphosphate (IP(3)) underlies the oscillatory
      changes in the concentration of intracellular free calcium ions ([Ca(2+)](i))
      seen during mammalian fertilization. IP(3) promotes Ca(2+) release in eggs by
      binding to its receptor, the type-1 IP(3) receptor (IP(3)R-1, also known as
      ITPR1), a ligand-gated Ca(2+) channel located in the membrane of the endoplasmic
      reticulum, the main Ca(2+) store of the cell. While IP(3)R-1 has been shown to
      mediate all Ca(2+) release during mouse fertilization, whether or not it plays
      such an essential role in fertilization-induced Ca(2+) release in large domestic
      species such as bovine and porcine is presently not known. Accordingly, we have
      generated metaphase II bovine eggs with a approximately 70%-80% reduction in the
      number of intact IP(3)R-1 by inducing receptor down-regulation during oocyte
      maturation. We did so by injecting the nonhydrolyzable IP(3) analogue,
      adenophostin A. Functional Ca(2+) release analysis revealed that IP(3)R-1 is the
      predominant Ca(2+) release channel in bovine eggs, requiring as little as 20% of
      total intact receptor to mount persistent [Ca(2+)](i) oscillations in response to
      fertilization, expression of PLCzeta (also known as PLCZ1), and adenophostin A.
      However, lower concentrations of IP(3) and near-physiological concentrations of
      porcine sperm extract were unable to trigger [Ca(2+)](i) oscillations in this
      reduced IP(3)R-1 model. Furthermore, we present evidence that the sensitivity of
      bovine IP(3)R-1 is impaired at the first embryonic interphase. Together, these
      results demonstrate the essential role of IP(3)R-1-mediated Ca(2+) release during
      fertilization in bovine eggs, and identify cell cycle regulatory mechanisms of
      [Ca(2+)](i) oscillations at the level of IP(3)R-1.

PMID- 15744022
TI  - Ubiquitin C-terminal hydrolase L-1 is essential for the early apoptotic wave of
      germinal cells and for sperm quality control during spermatogenesis.
AB  - Ubiquitination is required throughout all developmental stages of mammalian
      spermatogenesis. Ubiquitin C-terminal hydrolase (UCH) L1 is thought to associate
      with monoubiquitin to control ubiquitin levels. Previously, we found that UCHL1
      deficient testes of gad mice have reduced ubiquitin levels and are resistant to
      cryptorchid stress-related injury. Here, we analyzed the function of UCHL1 during
      the first round of spermatogenesis and during sperm maturation, both of which are
      known to require ubiquitin-mediated proteolysis. Testicular germ cells in the
      immature testes of gad mice were resistant to the early apoptotic wave that
      occurs during the first round of spermatogenesis. TUNEL staining and cell
      quantitation demonstrated decreased germ cell apoptosis and increased numbers of
      premeiotic germ cells in gad mice between Postnatal Days 7 and 14. Expression of
      the apoptotic proteins TRP53, Bax, and caspase-3 was also significantly lower in
      the immature testes of gad mice. In adult gad mice, cauda epididymidis weight,
      sperm number in the epididymis, and sperm motility were reduced. Moreover, the
      number of defective spermatozoa was significantly increased; however, complete
      infertility was not detected. These data indicate that UCHL1 is required for
      normal spermatogenesis and sperm quality control and demonstrate the importance
      of UCHL1-dependent apoptosis in spermatogonial cell and sperm maturation.

PMID- 15744021
TI  - Generation and characterization of pluripotent stem cells from cloned bovine
      embryos.
AB  - Bovine embryonic stem (ES) cell lines reported to date vary in morphology and
      marker expression (e.g., alkaline phosphatase [ALPL], stage-specific embryonic
      antigen 4 [SSEA4], and OCT4) that normally are associated with the
      undifferentiated, pluripotent state. These observations suggest that the proper
      experimental conditions for consistently producing bovine ES cells have not been
      identified. Here, we report three bovine ES cell lines, one from in vitro
      fertilized and two from nuclear transfer embryos. These bovine ES cells grew in
      large, multicellular colonies resembling the mouse ES and embryonic germ (EG)
      cells and human EG cells. Throughout the culture period, most of the cells within
      the colonies stained positive for ALPL and the cell surface markers SSEA4 and
      OCT4. The staining patterns of nuclear transfer ES cells were identical to those
      of the blastocysts generated in vitro yet different from most previously reported
      bovine ES cell lines, which were either negative or not detected. After
      undifferentiated culture for more than 1 yr, these cells maintained the ability
      to differentiate into embryoid bodies and derivatives of all three EG layers,
      thus demonstrating their pluripotency. However, unlike the mouse and human ES
      cells, following treatment with trypsin, type IV collagenase, or protease E, our
      bovine ES cells failed to self-renew and became spontaneously differentiated.
      Presumably, this resulted from an interruption of the self-renewal pathway. In
      summary, we generated pluripotent bovine ES cells with morphology similar to
      those of established ES cells in humans and mice as well as marker-staining
      patterns identical to those of the bovine blastocysts.

PMID- 15744023
TI  - Identification of novel and known oocyte-specific genes using complementary DNA
      subtraction and microarray analysis in three different species.
AB  - The main objective of the present study was to identify novel oocyte-specific
      genes in three different species: bovine, mouse, and Xenopus laevis. To achieve
      this goal, two powerful technologies were combined: a polymerase chain reaction
      (PCR)-based cDNA subtraction, and cDNA microarrays. Three subtractive libraries
      consisting of 3456 clones were established and enriched for oocyte-specific
      transcripts. Sequencing analysis of the positive insert-containing clones
      resulted in the following classification: 53% of the clones corresponded to known
      cDNAs, 26% were classified as uncharacterized cDNAs, and a final 9% were
      classified as novel sequences. All these clones were used for cDNA microarray
      preparation. Results from these microarray analyses revealed that in addition to
      already known oocyte-specific genes, such as GDF9, BMP15, and ZP, known genes
      with unknown function in the oocyte were identified, such as a MLF1-interacting
      protein (MLF1IP), B-cell translocation gene 4 (BTG4), and phosphotyrosine-binding
      protein (xPTB). Furthermore, 15 novel oocyte-specific genes were validated by
      reverse transcription-PCR to confirm their preferential expression in the oocyte
      compared to somatic tissues. The results obtained in the present study confirmed
      that microarray analysis is a robust technique to identify true positives from
      the suppressive subtractive hybridization experiment. Furthermore, obtaining
      oocyte-specific genes from three species simultaneously allowed us to look at
      important genes that are conserved across species. Further characterization of
      these novel oocyte-specific genes will lead to a better understanding of the
      molecular mechanisms related to the unique functions found in the oocyte.

PMID- 15744024
TI  - Expression and contribution of three different isoforms of prostaglandin E
      synthase in the bovine endometrium.
AB  - Prostaglandins are involved in the regulation of several reproductive processes
      such as ovulation, luteolysis, and establishment of pregnancy. Prostaglandin E(2)
      (PGE(2)) appears to favor establishment of pregnancy in most mammals studied so
      far. The primary enzymes involved in the production of PGE(2) from arachidonic
      acid are cyclooxygenases and prostaglandin E synthases (PGES). Three PGES have
      been identified in humans, but in the bovine, microsomal PGES2 and cytosolic PGES
      genes have neither been cloned nor associated to any physiological processes. The
      present study was undertaken to clone bovine MPGES2 and CPGES and to report on
      their regulation in the endometrium during the estrous cycle. CPGES mRNA
      expression declines progressively during the cycle; its protein is not modulated
      according to a precise pattern. MPGES2 mRNA and protein expression decrease from
      the beginning of the cycle until Days 13-15 and then increase until ovulation.
      Immunohistochemical analysis reveals that both enzymes are located in luminal
      epithelial and glandular epithelial cells and at a lower level in stromal cells.
      In addition, using the bovine endometrial cell line BEND, where higher
      accumulation of PGE(2) is observed following treatment with phorbol 12-myristate
      13-actetate (PMA) and tumor necrosis factor-alpha (TNF-alpha), we have found an
      associated increase of MPGES1 and COX2 but not CPGES or MPGES2 protein
      expression. Together, our results suggest that MPGES1 is not the only PGES
      present in the bovine endometrium but is the main enzyme associated with
      increased PGE(2) production in vitro.

PMID- 15744025
TI  - Trophoblast migration under flow is regulated by endothelial cells.
AB  - During pregnancy, trophoblasts enter the uterine vasculature and are found in
      spiral arteries far upstream of uterine capillaries. It is unknown whether
      trophoblasts reach the spiral arteries by migration within blood vessels against
      blood flow or by intravasation directly into spiral arteries after interstitial
      migration. We have developed an in vitro system consisting of early gestation
      macaque monkey trophoblasts cocultured with uterine endothelial cells and have
      exposed the cells in a parallel plate flow chamber to physiological levels of
      shear stress. Videomicroscopy followed by quantitative image analysis revealed
      that the migratory activity (expressed as average displacement and average
      migration velocity) of trophoblasts cultured on top of endothelial cells remained
      unchanged between shear stresses of 1-30 dyne/cm(2) whereas activity of
      trophoblasts alone increased with increasing shear stress. When the direction of
      migration was assessed at 1 and 7.5 dyne/cm(2), the extent of migration against
      and with flow was roughly equal for both trophoblasts alone and cocultured
      trophoblasts. At shear stress levels of 15 and 30 dyne/cm(2), trophoblasts
      incubated alone showed a significant decrease in migration against flow and
      corresponding increased migration in the direction of flow. In contrast,
      trophoblasts cocultured with uterine endothelial cells maintained the same extent
      of migration against flow at all shear stress levels. Migration against flow was
      also maintained when trophoblasts were cultured with endothelial cell-conditioned
      medium or fixed endothelial cells. The results indicate that factors expressed on
      the surface of uterine endothelial cells and factors released by endothelial
      regulate trophoblast migration under flow.

PMID- 15744026
TI  - Numbers of antral follicles during follicular waves in cattle: evidence for high
      variation among animals, very high repeatability in individuals, and an inverse
      association with serum follicle-stimulating hormone concentrations.
AB  - The extent, causes, and physiological significance of the variation in number of
      follicles growing during ovarian follicular waves in human beings and cattle are
      unknown. Therefore, the present study examined the variability and repeatability
      in numbers of follicles 3 mm or greater in diameter during the follicular waves
      in bovine estrous cycles, and we determined if the variation in number of
      follicles during waves was associated with alterations in secretion of FSH,
      estradiol, inhibin, and insulin-like growth factor I (IGF-I). Dairy cattle were
      subjected to twice-daily ultrasound analysis to count total number of antral
      follicles 3 mm or greater in diameter throughout 138 different follicular waves.
      In another study, blood samples were taken at frequent intervals from cows that
      consistently had low or very high numbers of follicles during waves and were
      subjected to immunoassays. Results indicate the following: First, despite an
      approximately sevenfold variation in number of follicles during waves among
      animals and marked differences in age, stage of lactation, and season of the
      year, a very highly repeatable (0.95) number of follicles 3 mm or greater in
      diameter is maintained during the ovulatory and nonovulatory follicular waves of
      individuals. Second, variation in number of follicles 3 mm or greater in diameter
      during waves and the inverse association of number of follicles during waves with
      FSH are not directly explained by alterations in the patterns of secretion of
      estradiol, inhibin, or IGF-I. Third, ovarian ultrasound analysis can be used
      reliably by investigators to identify cattle that consistently have low or high
      numbers of follicles during waves, thus providing a novel experimental model to
      determine the causes and physiological significance of the high variation in
      antral follicle number during follicular waves among single-ovulating species,
      such as cattle or humans.

PMID- 15744027
TI  - Green fluorescent protein labeling of primordial germ cells using a nontransgenic
      method and its application for germ cell transplantation in salmonidae.
AB  - Transplanting primordial germ cells (PGCs) has a number of potential applications
      in fish bioengineering. Previously, we established a system to visualize live
      PGCs in the rainbow trout by introducing the green fluorescent protein (Gfp) gene
      driven by rainbow trout vasa gene regulatory regions. However, for PGC
      transplantation to be practically useful in aquaculture, visualization of PGCs
      using a nontransgenic technique is required. In this study, we demonstrate a
      method for labeling PGCs from various fish species by introducing chimeric RNAs
      composed of the Gfp coding region and vasa gene 3'-untranslated regions (UTRs);
      these sequences play a critical role in stabilizing mRNA in zebrafish PGCs. The
      GFP chimeric RNAs, including vasa 3'-UTR RNAs from rainbow trout, Nibe croaker,
      and zebrafish, were microinjected into the cytoplasm of fertilized eggs of
      several Salmonidae species. All the resulting embryos showed specific labeling in
      PGCs after the somatogenesis stage, which continued to be visible for at least 50
      days. To apply this technique to PGC transplantation, PGCs labeled with chimeric
      RNA were microinjected into the peritoneal cavity of newly hatched salmonid
      embryos. The GFP labeling was sufficiently long-lived for the initial stage of
      donor PGC behavior to be followed in the recipient embryos. Importantly, donor
      PGCs from brown trout and masu salmon were incorporated into xenogeneic genital
      ridges in recipient rainbow trout. This nontransgenic method for labeling fish
      PGCs should be extremely useful for applications of PGC transplantation where the
      resulting progeny are to be released into the environment, such as PGC
      cryopreservation for fish stocks and surrogate brood stock technology.

PMID- 15744028
TI  - Homozygosity for a frequent and weakly penetrant predisposing allele at the RET
      locus in sporadic Hirschsprung disease.

PMID- 15744029
TI  - A missense mutation in the type II hair keratin hHb3 is associated with
      monilethrix.

PMID- 15744030
TI  - Phenotypic expression of double heterozygosity for BRCA1 and BRCA2 germline
      mutations.

PMID- 15744032
TI  - Reappraisal of the historical selective pressures for the CCR5-Delta32 mutation.
AB  - HIV strains are unable to enter macrophages that carry the CCR5-Delta32 deletion;
      the average frequency of this allele is 10% in European populations. A
      mathematical model based on the changing demography of Europe from 1000 to 1800
      AD demonstrates how plague epidemics, 1347 to 1670, could have provided the
      selection pressure that raised the frequency of the mutation to the level seen
      today. It is suggested that the original single mutation appeared over 2500 years
      ago and that persistent epidemics of a haemorrhagic fever that struck at the
      early classical civilisations served to force up the frequency to about 5x10(-5)
      at the time of the Black Death in 1347.

PMID- 15744031
TI  - The genetics of schizophrenia and bipolar disorder: dissecting psychosis.
AB  - Much work has been done to identify susceptibility genes in schizophrenia and
      bipolar disorder. Several well established linkages have emerged in
      schizophrenia. Strongly supported regions are 6p24-22, 1q21-22, and 13q32-34,
      while other promising regions include 8p21-22, 6q16-25, 22q11-12, 5q21-q33, 10p15
      p11, and 1q42. Genomic regions of interest in bipolar disorder include 6q16-q22,
      12q23-q24, and regions of 9p22-p21, 10q21-q22, 14q24-q32, 13q32-q34, 22q11-q22,
      and chromosome 18. Recently, specific genes or loci have been implicated in both
      disorders and, crucially, replicated. Current evidence supports NRG1, DTNBP1,
      DISC1, DAOA(G72), DAO, and RGS4 as schizophrenia susceptibility loci. For bipolar
      disorder the strongest evidence supports DAOA(G72) and BDNF. Increasing evidence
      suggests an overlap in genetic susceptibility across the traditional
      classification systems that dichotomised psychotic disorders into schizophrenia
      or bipolar disorder, most notably with association findings at DAOA(G72), DISC1,
      and NRG1. Future identification of psychosis susceptibility genes will have a
      major impact on our understanding of disease pathophysiology and will lead to
      changes in classification and the clinical practice of psychiatry.

PMID- 15744033
TI  - Association of partial AZFc region deletions with spermatogenic impairment and
      male infertility.
AB  - BACKGROUND: Complete deletions of the AZFc region in distal Yq are the most
      frequent molecular genetic cause of severe male infertility. They are caused by
      intrachromosomal homologous recombination between amplicons--large, nearly
      identical repeats--and are found in 5-10% of cases of azoospermia and severe
      oligozoospermia. Homologous recombination may also generate different partial
      deletions of AZFc, but their contribution to spermatogenic impairment has not
      been confirmed. METHODS: In this study we analysed the prevalence and
      characteristics of different partial AZFc deletions and their association with
      spermatogenic failure. We studied 337 infertile men with different spermatogenic
      impairment and 263 normozoospermic fertile men using AZFc specific sequence
      tagged site markers and DAZ specific single nucleotide variants. RESULTS: We
      identified 18 cases of partial AZFc deletions in the infertile group (5.3%) and
      one case in the control group (0.4%). Seventeen deletions had the "gr/gr"
      pattern, one the "b2/b3" pattern, and one represented a novel deletion with
      breakpoints in b3 and b4 amplicons. Partial AZFc deletions were associated with
      different spermatogenic phenotypes ranging from complete azoospermia to only
      moderate oligozoospermia. CONCLUSIONS: Together with published data, our analysis
      of DAZ gene copy suggested that the contribution of the different deletions to
      male infertility varies: only partial AZFc deletions removing DAZ1/DAZ2 seem to
      be associated with spermatogenic impairment, whereas those removing DAZ3/DAZ4 may
      have no or little effect on fertility. These data show that, beside complete AZFc
      deletions, specific partial deletions represent a risk factor for male
      infertility, even if with different effect on spermatogenesis.

PMID- 15744035
TI  - A survey of haplotype variants at several disease candidate genes: the importance
      of rare variants for complex diseases.
AB  - BACKGROUND: The haplotype based association method offers a powerful approach to
      complex disease gene mapping. In this method, a few common haplotypes that
      account for the vast majority of chromosomes in the populations are usually
      examined for association with disease phenotypes. This brings us to a critical
      question of whether rare haplotypes play an important role in influencing disease
      susceptibility and thus should not be ignored in the design and execution of
      association studies. METHODS: To address this question we surveyed, in a large
      sample of 1873 white subjects, six candidate genes for osteoporosis (a common
      late onset bone disorder), which had 29 SNPs, an average marker density of 13 kb,
      and covered a total of 377 kb of the DNA sequence. RESULTS: Our empirical data
      demonstrated that two rare haplotypes of the parathyroid hormone (PTH)/PTH
      related peptide receptor type 1 and vitamin D receptor genes (PTHR1 and VDR) with
      frequencies of 1.1% and 2.9%, respectively, had significant effects on
      osteoporosis phenotypes (p = 4.2 x 10(-6) and p = 1.6 x 10(-4), respectively).
      Large phenotypic differences (4.0 approximately 5.0%) were observed between
      carriers of these rare haplotypes and non-carriers. Carriers of the two rare
      haplotypes showed quantitatively continuous variation in the population and were
      derived from a wide spectrum rather than from one extreme tail of the population
      phenotype distribution. CONCLUSIONS: These findings indicate that rare
      haplotypes/variants are important for disease susceptibility and cannot be
      ignored in genetics studies of complex diseases. The study has profound
      implications for association studies and applications of the HapMap project.

PMID- 15744034
TI  - Lamin A N-terminal phosphorylation is associated with myoblast activation:
      impairment in Emery-Dreifuss muscular dystrophy.
AB  - BACKGROUND: Skeletal muscle disorders associated with mutations of lamin A/C gene
      include autosomal Emery-Dreifuss muscular dystrophy and limb girdle muscular
      dystrophy 1B. The pathogenic mechanism underlying these diseases is unknown.
      Recent data suggest an impairment of signalling mechanisms as a possible cause of
      muscle malfunction. A molecular complex in muscle cells formed by lamin A/C,
      emerin, and nuclear actin has been identified. The stability of this protein
      complex appears to be related to phosphorylation mechanisms. OBJECTIVE: To
      analyse lamin A/C phosphorylation in control and laminopathic muscle cells.
      METHODS: Lamin A/C N-terminal phosphorylation was determined in cultured mouse
      myoblasts using a specific antibody. Insulin treatment of serum starved myoblast
      cultures was carried out to evaluate involvement of insulin signalling in the
      phosphorylation pathway. Screening of four Emery-Dreifuss and one limb girdle
      muscular dystrophy 1B cases was undertaken to investigate lamin A/C
      phosphorylation in both cultured myoblasts and mature muscle fibres. RESULTS:
      Phosphorylation of lamin A was observed during myoblast differentiation or
      proliferation, along with reduced lamin A/C phosphorylation in quiescent
      myoblasts. Lamin A N-terminus phosphorylation was induced by an insulin stimulus,
      which conversely did not affect lamin C phosphorylation. Lamin A/C was also
      hyperphosphorylated in mature muscle, mostly in regenerating fibres. Lamin A/C
      phosphorylation was strikingly reduced in laminopathic myoblasts and muscle
      fibres, while it was preserved in interstitial fibroblasts. CONCLUSIONS: Altered
      lamin A/C interplay with a muscle specific phosphorylation partner might be
      involved in the pathogenic mechanism of Emery-Dreifuss muscular dystrophy and
      limb girdle muscular dystrophy 1B.

PMID- 15744036
TI  - Vitamin D receptor gene polymorphisms are linked to and associated with adult
      height.
AB  - BACKGROUND: The vitamin D receptor (VDR) gene is important to human stature, as
      it mediates metabolic pathways, calcium homeostasis, and phosphate homeostasis,
      which influence growth. METHODS: We examined the relationship between VDR and
      adult height in 1873 white subjects from 406 nuclear families. Four SNPs, namely 
      4817A/G at intron 1, FokI C/T at exon 2 start codon, BsmI A/G at intron 8, and
      TaqI T/C at exon 9 in VDR were tested for linkage and association with adult
      height variation by the program QTDT (quantitative transmission disequilibrium
      test). The bT haplotype of the BsmI and TaqI loci was further tested for its
      association with height in unrelated samples randomly chosen from the 406 nuclear
      families by traditional population association methods. RESULTS: All four tested
      SNPs were linked to adult height. Within family associations with height were
      detected at BsmI and TaqI loci (p = 0.048 and 0.039, respectively). Analyses
      based on BsmI/TaqI haplotypes also revealed evidence for linkage (p = 0.05) and
      association (p = 0.001) with height. The bT haplotype was significantly
      associated with higher adult height (p = 0.033, within family association test).
      Such an association might be female specific and influenced by menstrual status.
      CONCLUSIONS: Our results strongly suggest that VDR may be linked to and
      associated with adult height variation in white populations.

PMID- 15744037
TI  - Linkage to the FOXC2 region of chromosome 16 for varicose veins in otherwise
      healthy, unselected sibling pairs.
AB  - BACKGROUND: The FOXC2 gene on 16q24 is mutated in lymphoedema distichiasis (LD),
      in which varicose veins (VV) are a common feature. We hypothesised that this gene
      might be implicated in the development of VV in the normal population, therefore,
      after performing a classical twin study, we tested for linkage and association in
      white women. We also tested for linkage with haemorrhoids (H), as a separate
      venous anomaly at the same locus. METHODS: A total of 2060 complete female twin
      pairs aged 18-80 years from the St Thomas' Adult UK Twin registry replied to
      questions on VV and H as part of a broader postal survey of 6600 twins (62%
      response rate). Dizygotic female twin pairs were tested for linkage and
      association to the candidate marker D16S520 (1903 individuals genotyped), which
      is located about 80 kb from FOXC2. RESULTS: Casewise concordance rates were
      significantly higher for monozygotic than dizygotic twins for both phenotypes (VV
      67% v 45%; p = 2.2x10(-6); H 68% v 59%; p = 0.01; H including during pregnancy
      73% v 64%; p = 2.1x10(-4)), corresponding to additive genetic heritabilities in
      liability of 86% (95% confidence interval (CI) 73% to 99%) for VV and 56-61% for
      H (95% CI 43% to 73%). The presence of VV and H were significantly correlated. We
      found significant evidence of linkage to the marker for VV (MLS(ASP) = 1.37, p =
      0.01; GLM(ASP/DSP) Z = 3.17 p = 0.002), but no association. Both linkage and
      association tests were negative for H. The combined phenotype of having VV and H
      did not show any evidence of linkage or association. CONCLUSION: These results
      demonstrate VV and H to be heritable, related conditions, and the data strongly
      suggest FOXC2 to be implicated in the development of VV in the general
      population.

PMID- 15744038
TI  - Association of oestrogen receptor alpha gene polymorphisms with postmenopausal
      bone loss, bone mass, and quantitative ultrasound properties of bone.
AB  - BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate
      bone mineral density (BMD) and other determinants of osteoporotic fracture risk.
      OBJECTIVE: To investigate the relation between common polymorphisms and
      haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population
      based cohort of 3054 Scottish women. RESULTS: There was a significant association
      between a common haplotype "px", defined by the PvuII and XbaI restriction
      fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck
      bone loss in postmenopausal women who had not received hormone replacement
      therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were
      approximately 14% higher in subjects who carried one copy of px and 22% higher in
      those who carried two copies, compared with those who did not carry the px
      haplotype. The px haplotype was associated with lower femoral neck BMD in the
      postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound
      attenuation (BUA) values in the whole study population (p = 0.005). There was no
      association between a TA repeat polymorphism in the ESR1 promoter and any
      phenotype studied, though on long range haplotype analysis subjects with a
      smaller number of TA repeats who also carried the px haplotype had reduced BUA
      values. CONCLUSIONS: The ESR1px haplotype is associated with reduced hip BMD
      values and increased rates of femoral neck bone loss in postmenopausal women. An
      association with BUA may explain the fact that ESR1 intron 1 alleles predict
      osteoporotic fractures by a mechanism partly independent of differences in BMD.

PMID- 15744039
TI  - Effects of enzyme replacement therapy on pain and health related quality of life
      in patients with Fabry disease: data from FOS (Fabry Outcome Survey).
AB  - BACKGROUND: Fabry disease is an X linked lysosomal storage disease caused by
      deficiency of the lysosomal enzyme alpha-galactosidase A. This leads to
      accumulation of globotriaosylceramide in nearly all tissues, including the blood
      vessels, kidney, myocardium, and nervous system. Symptoms often begin in
      childhood and include acroparaesthesia, with burning or tingling pain that
      spreads from the extremities to more proximal sites. AIMS: This study set out to
      evaluate pain and its influence on quality of life in patients with Fabry disease
      receiving enzyme replacement therapy (ERT) with agalsidase alfa. METHODS: Data
      were obtained from the Fabry Outcome Survey. Pain was measured using the Brief
      Pain Inventory (BPI), and health-related quality of life (HRQoL) was documented
      with the European Quality of Life Questionnaire (EQ-5D). RESULTS: The mean (SD)
      score for "pain at its worst" on the BPI prior to ERT was 5.1 (2.7). One year
      after commencement of ERT, this had improved by 0.5, and improved by a further
      0.6 after 2 years (p<0.05). Similar statistically significant improvements were
      seen for "pain on average" and "pain now" after 2 years of ERT. The mean HRQoL
      utility score prior to ERT was 0.66 (0.32). After 12 months of treatment with
      agalsidase alfa, this had improved to 0.74 (0.26; p<0.05); this improvement was
      maintained after 2 years. CONCLUSIONS: ERT with agalsidase alfa significantly
      reduces pain and improves quality of life in patients with Fabry disease.

PMID- 15744040
TI  - Assignment of a new congenital fibrosis of extraocular muscles type 3 (CFEOM3)
      locus, FEOM4, based on a balanced translocation t(2;13) (q37.3;q12.11) and
      identification of candidate genes.

PMID- 15744041
TI  - Homozygosity mapping of autosomal recessive demyelinating Charcot-Marie-Tooth
      neuropathy (CMT4H) to a novel locus on chromosome 12p11.21-q13.11.

PMID- 15744042
TI  - Confirmation of the association of the R620W polymorphism in the protein tyrosine
      phosphatase PTPN22 with type 1 diabetes in a family based study.

PMID- 15744043
TI  - MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis
      imperfecta.

PMID- 15744044
TI  - Complete allelic analysis of BRCA1 and BRCA2 variants in young Nigerian breast
      cancer patients.

PMID- 15744045
TI  - Prevalence and phenotype of subjects carrying rare variants in the Italian
      registry for alpha1-antitrypsin deficiency.

PMID- 15744046
TI  - Will humans join the club?

PMID- 15744047
TI  - Oxidative mutagenesis, mismatch repair, and aging.
AB  - A PubMed search for the term "oxidative stress" yields over 29,000 articles
      published on the subject over the past 10 years; more than 2000 of these articles
      also include the term "aging" in their title or abstract. Many theories of aging
      predict causal roles for oxidative stress in the myriad of pathological changes
      that occur as a function of age, including an increasing propensity to develop
      cancer. A possible link between aging and cancer is the induction and
      accumulation of somatic mutations caused by oxidative stress. This Review focuses
      on small mutational events that are induced by oxidative stress and the role of
      mismatch repair (MMR) in preventing their formation. It also discusses a possible
      inhibitory effect of oxidative stress on MMR. We speculate that a synergistic
      interaction between oxidative damage to DNA and reduced MMR levels will, in part,
      account for an accumulation of small mutational events, and hence cancer, with
      aging.

PMID- 15744048
TI  - A genetic screen in Drosophila for identifying novel components of the hedgehog
      signaling pathway.
AB  - The Hedgehog signaling pathway plays an essential role in the pattern formation
      and development of metazoan animals. Misregulation of Hedgehog signaling has also
      been associated with the formation of multiple types of cancer. For these
      reasons, the Hedgehog pathway has attracted considerable interest. Many proteins
      required in the Hedgehog pathway have been identified, and while much has been
      learned about their function in signal transduction, it is clear that this
      complement of proteins does not comprise the full set necessary for Hedgehog
      signal transduction. Because significant gaps remain in our knowledge of the
      molecules required for Hedgehog signaling, we performed an enhancer/suppressor
      screen in Drosophila melanogaster to identify novel components of the pathway. In
      addition to the isolation of new alleles of the known pathway components patched
      and smoothened, this screen identified 14 novel complementation groups and a
      larger number of loci represented by single alleles. These groups include
      mutations in the genes encoding the translation factors eRF1 and eIF1A and the
      kinesin-like protein Pavarotti. It also identified mutations in a gene whose
      product is necessary for the movement of Hedgehog protein through tissues.

PMID- 15744049
TI  - Maternal transmission ratio distortion at the mouse Om locus results from meiotic
      drive at the second meiotic division.
AB  - We have observed maternal transmission ratio distortion (TRD) in favor of DDK
      alleles at the Ovum mutant (Om) locus on mouse chromosome 11 among the offspring
      of (C57BL/6 x DDK) F(1) females and C57BL/6 males. Although significant lethality
      occurs in this backcross ( approximately 50%), differences in the level of TRD
      found in recombinant vs. nonrecombinant chromosomes among offspring argue that
      TRD is due to nonrandom segregation of chromatids at the second meiotic division,
      i.e., true meiotic drive. We tested this hypothesis directly, by determining the
      centromere and Om genotypes of individual chromatids in zygote stage embryos. We
      found similar levels of TRD in favor of DDK alleles at Om in the female
      pronucleus and TRD in favor of C57BL/6 alleles at Om in the second polar body. In
      those embryos for which complete dyads have been reconstructed, TRD was present
      only in those inheriting heteromorphic dyads. These results demonstrate that
      meiotic drive occurs at MII and that preferential death of one genotypic class of
      embryo does not play a large role in the TRD.

PMID- 15744050
TI  - Revisiting purine-histidine cross-pathway regulation in Saccharomyces cerevisiae:
      a central role for a small molecule.
AB  - Because some metabolic intermediates are involved in more than one pathway,
      crosstalk between pathways is crucial to maintaining homeostasis. AMP and
      histidine biosynthesis pathways are coregulated at the transcriptional level in
      response to adenine availability. 5'-Phosphoribosyl-4-carboxamide-5
      aminoimidazole (AICAR), a metabolic intermediate at the crossroads between these
      two pathways, is shown here to be critical for activation of the transcriptional
      response in the absence of adenine. In this study, we show that both AMP and
      histidine pathways significantly contribute to AICAR synthesis. Furthermore, we
      show that upregulation of the histidine pathway clearly interferes with
      regulation of the AMP pathway, thus providing an explanation for the regulatory
      crosstalk between these pathways. Finally, we revisit the histidine auxotrophy of
      ade3 or ade16 ade17 mutants. Interestingly, overexpression of PMU1, encoding a
      potential phosphomutase, partially suppresses the histidine requirement of an
      ade3 ade16 ade17 triple mutant, most probably by reducing the level of AICAR in
      this mutant. Together our data clearly establish that AICAR is not just a
      metabolic intermediate but also acts as a true regulatory molecule.

PMID- 15744051
TI  - Evidence that Spt10 and Spt21 of Saccharomyces cerevisiae play distinct roles in
      vivo and functionally interact with MCB-binding factor, SCB-binding factor and
      Snf1.
AB  - Mutations in SPT10 and SPT21 of Saccharomyces cerevisiae have been previously
      shown to cause two prominent mutant phenotypes: (1) defects in transcription of
      particular histone genes and (2) suppression of Ty and delta-insertion mutations
      (Spt(-) phenotype). The requirement for Spt10 and Spt21 for transcription of
      particular histone genes suggested that they may interact with two factors
      previously shown to be present at histone loci, SBF (Swi4 and Swi6) and MBF (Mbp1
      and Swi6). Therefore, we have studied swi4Delta, mbp1Delta, and swi6Delta mutants
      with respect to histone gene transcription and for interactions with spt10Delta
      and spt21Delta. Our results suggest that MBF and SBF play only modest roles in
      activation of histone gene transcription. In addition, we were surprised to find
      that swi4Delta, mbp1Delta, and swi6Delta mutations suppress the spt21Delta Spt(-)
      phenotype, but not the spt21Delta defect in histone gene transcription. In
      contrast, both swi4Delta and mbp1Delta cause lethality when combined with
      spt10Delta. To learn more about mutations that can suppress the spt21Delta Spt(-)
      phenotype, we performed a genetic screen and identified spt21Delta suppressors in
      seven additional genes. Three of these spt21Delta suppressors also cause
      lethality when combined with spt10Delta. Analysis of one spt21Delta suppressor,
      reg1, led to the finding that hyperactivation of Snf1 kinase, as caused by
      reg1Delta, suppresses the Spt(-) phenotype of spt21Delta. Taken together, these
      genetic interactions suggest distinct roles for Spt21 and Spt10 in vivo that are
      sensitive to multiple perturbations in transcription networks.

PMID- 15744052
TI  - Comparative genomics and diversifying selection of the clustered vertebrate
      protocadherin genes.
AB  - To explain the mechanism for specifying diverse neuronal connections in the
      brain, Sperry proposed that individual cells carry chemoaffinity tags on their
      surfaces. The enormous complexity of these connections requires a tremendous
      diversity of cell-surface proteins. A large number of neural transmembrane
      protocadherin (Pcdh) proteins is encoded by three closely linked human and mouse
      gene clusters (alpha, beta, and gamma). To gain insight into Pcdh evolution, I
      performed comprehensive comparative cDNA and genomic DNA analyses for the three
      clusters in the chimpanzee, rat, and zebrafish genomes. I found that there are
      species-specific duplications in vertebrate Pcdh genes and that additional
      diversity is generated through alternative splicing within the zebrafish
      "variable" and "constant" regions. Moreover, different codons (sites) in the
      mammalian Pcdh ectodomains (ECs) are under diversifying selection, with some
      under diversity-enhancing positive Darwinian selection and others, including
      calcium-binding sites, under strong purifying selection. Interestingly, almost
      all positively selected codon positions are located on the surface of ECs 2 and
      3. These diversified residues likely play an important role in combinatorial
      interactions of Pcdh proteins, which could provide the staggering diversity
      required for neuronal connections in the brain. These results also suggest that
      adaptive selection is an additional evolutionary factor for increasing Pcdh
      diversity.

PMID- 15744054
TI  - Synthetic lethality of retinoblastoma mutant cells in the Drosophila eye by
      mutation of a novel peptidyl prolyl isomerase gene.
AB  - Mutations that inactivate the retinoblastoma (Rb) pathway are common in human
      tumors. Such mutations promote tumor growth by deregulating the G1 cell cycle
      checkpoint. However, uncontrolled cell cycle progression can also produce new
      liabilities for cell survival. To uncover such liabilities in Rb mutant cells, we
      performed a clonal screen in the Drosophila eye to identify second-site mutations
      that eliminate Rbf(-) cells, but allow Rbf(+) cells to survive. Here we report
      the identification of a mutation in a novel highly conserved peptidyl prolyl
      isomerase (PPIase) that selectively eliminates Rbf(-) cells from the Drosophila
      eye.

PMID- 15744055
TI  - Differential activation of M26-containing meiotic recombination hot spots in
      Schizosaccharomyces pombe.
AB  - Certain genomic loci, termed hot spots, are predisposed to undergo genetic
      recombination during meiosis at higher levels relative to the rest of the genome.
      The factors that specify hot-spot potential are not well understood. The M26 hot
      spot of Schizosaccharomyces pombe is dependent on certain trans activators and a
      specific nucleotide sequence, which can function as a hot spot in a position- and
      orientation-independent fashion within ade6. In this report we demonstrate that a
      linear element (LE) component, Rec10, has a function that is required for
      activation of some, but not all, M26-containing hot spots and from this we
      propose that, with respect to hot-spot activity, there are three classes of M26
      containing sequences. We demonstrate that the localized sequence context in which
      the M26 heptamer is embedded is a major factor governing whether or not this
      Rec10 function is required for full hot-spot activation. Furthermore, we show
      that the rec10-144 mutant, which is defective in full activation of ade6-M26, but
      proficient for activation of other M26-containing hot spots, is also defective in
      the formation of LEs, suggesting an intimate link between higher-order chromatin
      structure and local influences on hot-spot activation.

PMID- 15744053
TI  - Lineage-specific loss of function of bitter taste receptor genes in humans and
      nonhuman primates.
AB  - Since the process of becoming dead genes or pseudogenes (pseudogenization) is
      irreversible and can occur rather rapidly under certain environmental
      circumstances, it is one plausible determinant for characterizing species
      specificity. To test this evolutionary hypothesis, we analyzed the tempo and mode
      of duplication and pseudogenization of bitter taste receptor (T2R) genes in
      humans as well as in 12 nonhuman primates. The results show that primates have
      accumulated more pseudogenes than mice after their separation from the common
      ancestor and that lineage-specific pseudogenization becomes more conspicuous in
      humans than in nonhuman primates. Although positive selection has operated on
      some amino acids in extracellular domains, functional constraints against T2R
      genes are more relaxed in primates than in mice and this trend has culminated in
      the rapid deterioration of the bitter-tasting capability in humans. Since T2R
      molecules play an important role in avoiding generally bitter toxic and harmful
      substances, substantial modification of the T2R gene repertoire is likely to
      reflect different responses to changes in the environment and to result from
      species-specific food preference during primate evolution.

PMID- 15744057
TI  - Evolution of human immunodeficiency virus under selection and weak recombination.
AB  - To predict emergence of drug resistance in patients undergoing antiretroviral
      therapy, we study accumulation of preexisting beneficial alleles in a haploid
      population of N genomes. The factors included in the model are selection with the
      coefficient s and recombination with the small rate per genome r (r << s sqrt of
      k, where k is the average number of less-fit loci per genome). Mutation events
      are neglected. To describe evolution at a large number of linked loci, we
      generalize the analytic method we developed recently for an asexual population.
      We show that the distribution of genomes over the deleterious allele number moves
      in time as a "solitary wave" that is quasi-deterministic in the middle (on the
      average) but has stochastic edges. We arrive at a single-locus expression for the
      average accumulation rate, in which the effects of linkage, recombination, and
      random drift are all accounted for by the effective selection coefficient s
      lnNr/lnNs(2)k/r. At large N, the effective selection coefficient approaches the
      single-locus value s. Below the critical size N(c) approximately 1/r, a
      population eventually becomes a clone, recombination cannot produce new
      sequences, and virus evolution stops. Taking into account finite mutation rate
      predicts a small, finite rate of evolution at N < N(c). We verify the accuracy of
      the results analytically and by Monte Carlo simulation. On the basis of our
      findings, we predict that partial depletion of the HIV population by combined
      anti-retroviral therapy can suppress emergence of drug-resistant strains.

PMID- 15744056
TI  - Alpha-synuclein targets the plasma membrane via the secretory pathway and induces
      toxicity in yeast.
AB  - A pathological feature of Parkinson's disease is the presence of Lewy bodies
      within selectively vulnerable neurons. These are ubiquitinated cytoplasmic
      inclusions containing alpha-synuclein, an abundant protein normally associated
      with presynaptic terminals. Point mutations in the alpha-synuclein gene (A30P and
      A53T), as well as triplication of the wild-type (WT) locus, have been linked to
      autosomal dominant Parkinson's. How these alterations might contribute to disease
      progression is unclear. Using the genetically tractable yeast Saccharomyces
      cerevisiae as a model system, we find that both the WT and the A53T isoforms of
      alpha-synuclein initially localize to the plasma membrane, to which they are
      delivered via the classical secretory pathway. In contrast, the A30P mutant
      protein disperses within the cytoplasm and does not associate with the plasma
      membrane, and its intracellular distribution is unaffected by mutations in the
      secretory pathway. When their expression is elevated, WT and A53T, but not A30P,
      are toxic to cells. At moderate levels of expression, WT and A53T induce the
      cellular stress (heat-shock) response and are toxic to cells bearing mutations in
      the 20S proteasome. Our results reveal a link between plasma membrane targeting
      of alpha-synuclein and its toxicity in yeast and suggest a role for the quality
      control (QC) system in the cell's effort to deal with this natively unfolded
      protein.

PMID- 15744058
TI  - The number of mutations selected during adaptation in a laboratory population of
      Saccharomyces cerevisiae.
AB  - There is currently limited empirical and theoretical support for the prevailing
      view that adaptation typically results from the fixation of many mutations, each
      with small phenotypic effects. Recent theoretical work suggests that, on the
      contrary, most of the phenotypic change during an episode of adaptation can
      result from the selection of a few mutations with relatively large effects. I
      studied the genetics of adaptation by populations of budding yeast to a culture
      regime of daily hundredfold dilution and transfer in a glucose-limited minimal
      liquid medium. A single haploid genotype isolated after 2000 generations showed a
      76% fitness increase over its ancestor. This evolved haploid was crossed with its
      ancestor, and tetrad dissections were used to isolate a complete series of six
      meiotic tetrads. The Castle-Wright estimator of the number of loci at which
      adaptive mutations had been selected, modified to account for linkage and
      variation among mutations in the size of their effect, is 4.4. The estimate for a
      second haploid genotype, isolated from a separate population and with a fitness
      gain of 60%, was 2.7 loci. Backcrosses to the ancestor with the first evolved
      genotype support the inference that adaptation resulted primarily from two to
      five mutations. These backcrosses also indicated that deleterious mutations had
      hitchhiked with adaptive mutations in this evolved genotype.

PMID- 15744059
TI  - Sialobiology of influenza: molecular mechanism of host range variation of
      influenza viruses.
AB  - The gene pool of influenza A viruses in aquatic birds provides all of the genetic
      diversity required for human and lower animals. Host range selection of the
      receptor binding specificity of the influenza virus hemagglutinin occurs during
      maintenance of the virus in different host cells that express different receptor
      sialo-sugar chains. In this paper, functional roles of the hemagglutinin and
      neuraminidase spikes of influenza viruses are described in the relation to 1)
      host range of influenza viruses, 2) receptor binding specificity of human and
      other animal influenza viruses, 3) recognition of sialyl sugar chains by Spanish
      influenza virus hemagglutinin, 4) highly pathogenic and potentially pandemic
      H5N1, H9N2, and H7N7 avian influenza viruses and molecular mechanism of host
      range variation of influenza viruses, 5) role of the neuraminidase spike for the
      host range of influenza viruses, and 6) Development of anti-influenza drugs.

PMID- 15744060
TI  - Involvement of Ca2+/calmodulin-dependent protein kinase II in heparin-stimulated
      release of hepatic lipase activity from rat hepatocytes.
AB  - The release of hepatic lipase (HTGL), which is responsible for the hydrolysis of
      lipoprotein triacylglyceride, produced by heparin from the isolated rat
      hepatocytes in primary culture has been examined. Tyrosine kinase (TK) inhibitors
      (ST-638 and biochanin A) inhibited the heparin-stimulated release of HTGL
      activity. The activity of partially purified TK preparation from the hepatocytes
      was found to be increased following incubation with heparin in a manner which was
      both time- and dose-dependent. An intracellular Ca(2+)-chelator (Quin2/AM), a
      calmodulin inhibitor (W-7) and a Ca(2+)/calmodulin-dependent protein kinase II
      (CaMK-II) inhibitor (KN-93) suppressed the release of HTGL activity by heparin.
      In addition, CaMK-II activity in the hepatocytes incubated with heparin was
      recognized to elevate in a time- and dose-dependent manner. The increase in CaMK
      II activity by heparin was markedly reduced in the presence of the inhibitors of
      TK. These results suggest that the release of HTGL activity from the hepatocytes
      by heparin is, in part, caused through a pathway involving an activation of CaMK
      II associated with an increase in membrane TK activity.

PMID- 15744061
TI  - Molecular cloning and characterization of rat semicarbazide-sensitive amine
      oxidase.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) (EC 1.4.3.6) is widely distributed
      in nature and catalyzes the oxidative deamination of primary amines. Although
      SSAO full-length cDNA sequences have been reported for some mammalian species,
      only a partial 5'-terminal sequence has been confirmed in the rat. In this study
      we isolated full-length SSAO cDNA from rat aorta and examined its mRNA expression
      in various rat tissues by real-time PCR, as well as the subcellular and tissue
      distributions of SSAO activity. The deduced amino acid sequence showed 91% and
      80% identity with mouse and human SSAO, respectively. The mRNA was expressed in
      many rat tissues. Those findings were supported by the broad distribution of SSAO
      in the body. Thus, a high level of SSAO was shown in adipocytes by both mRNA
      expression and enzyme activity measurement. The results suggest that SSAO may
      play an important role in the degradation of biologically active amines in
      adipocytes.

PMID- 15744062
TI  - Radical species in DNA strand-cleavage caused by dihydropyrazines.
AB  - Dihydropyrazines (DHPs), which generate hydroxyl and carbon-centered radicals,
      cleaved DNA single-strand. It is new knowledge that DHPs were recently determined
      to produce 8-hydroxydeoxyguanosine. The remarkable increase in the DNA strand
      cleavage activity upon the addition of Cu2+ suggests that the primary reactive
      species is carbon-centered radicals rather than the hydroxyl radical generated
      the initiation reaction. This proposal was in fair agreement with of the observed
      carbon-centered radical signal intensity, but an effect was not observed with the
      increase in the hydroxyl radical signal intensity.

PMID- 15744063
TI  - Expression of annexin A3 in primary cultured parenchymal rat hepatocytes and
      inhibition of DNA synthesis by suppression of annexin A3 expression using RNA
      interference.
AB  - Annexin A3 is a member of the lipocortin/annexin family, which binds to
      phospholipids and membranes in a Ca(2+)-dependent manner. Although annexin A3 has
      various functions in vitro, its cellular significance is completely unknown.
      Annexin A3 is not found in rat liver in vivo. In the present study, we
      investigated the expression of annexin A3 in primary cultured parenchymal rat
      hepatocytes. Annexin A3 protein was detected in 48-h, but not 2.5-h, cultured
      hepatocytes using Western blot analysis. The annexin A3 level further increased
      after an additional 24 h of culture. Annexin A3 mRNA was not detected in 2.5-h
      cultured hepatocytes but was detected 22 h after the start of culture by RT-PCR
      analysis, reaching a maximum value after 48 h of culture. To define the role of
      Annexin A3 in DNA synthesis, RNA interference was used to reduce annexin III gene
      expression in hepatocytes. The transfection of small interfering RNAs targeting
      annexin A3 in the hepatocytes reduced the corresponding mRNA and protein
      expression by approximately 80% and more than 90%, respectively, at 24 h after
      transfection. In the annexin A3 small interfering RNAs-transfected cells, DNA
      synthesis, as assessed by [3H]thymidine incorporation, decreased by approximately
      70% not only in the control cultures, but also in the hepatocyte growth factor-
      or epidermal growth factor-treated cells. These findings show that annexin A3 is
      expressed in primary cultured parenchymal rat hepatocytes and that the
      suppression of annexin A3 expression using RNA interference inhibits DNA
      synthesis.

PMID- 15744064
TI  - Cloning and expression of a brain-specific putative UDP-GalNAc: polypeptide N
      acetylgalactosaminyltransferase gene.
AB  - We isolated a rat cDNA clone and its human orthologue, which are most homologous
      to UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase 9, by homology-based
      PCR from brain. Nucleotide sequence analysis of these putative GalNAc
      transferases (designated pt-GalNAc-T) showed that they contained structural
      features characteristic of the GalNAc-transferase family. It was also found that
      human pt-GalNAc-T was identical to the gene WBSCR17, which is reported to be in
      the critical region of patients with Williams-Beuren Syndrome, a
      neurodevelopmental disorder, and to be predominantly expressed in brain and
      heart. In order to investigate the expression of pt-GalNAc-T in brain in more
      detail, we first examined that of human pt-GalNAc-T by Northern blot analysis and
      found the expression of the 5.0-kb mRNA to be most abundant in cerebral cortex
      with somewhat less abundant in cellebellum. The expression of rat pt-GalNAc-T was
      investigated more extensively. The brain-specific expression of 2.0-kb and 5.0-kb
      transcripts was demonstrated by Northern blot analysis. In situ hybridization in
      the adult brain revealed high levels of expression in cerebellum, hippocampus,
      thalamus, and cerebral cortex. Moreover, observation at high magnification
      revealed the expression to be associated with neurons, but not with glial cells.
      Analysis of the rat embryos also demonstrated that rat pt-GalNAc-T was expressed
      in the nervous system, including in the diencephalons, cerebellar primordium, and
      dorsal root ganglion. However, recombinant human pt-GalNAc-T, which was expressed
      in insect cells, did not glycosylate several peptides derived from mammalian
      mucins, suggesting that it may have a strict substrate specificity. The brain
      specific expression of pt-GalNAc-T suggested its involvement in brain
      development, through O-glycosylation of proteins in the neurons.

PMID- 15744065
TI  - Catfish egg lectin causes rapid activation of multidrug resistance 1 P
      glycoprotein as a lipid translocase.
AB  - Rhamnose-binding lectin from catfish (Silurus asotus) eggs (SAL) has the ability
      to induce externalization of phosphatidylserine (PS), followed by cell shrinkage
      in globotriaosylceramide (Gb3)-expressing Burkitt's lymphoma Raji cells. Because
      phospholipid scramblase and aminophospholipid translocase did not participate in
      SAL-induced PS externalization, we examined the relationship of ATP-binding
      cassette (ABC) transporters, such as multidrug resistance (MDR) 1 P-glycoprotein
      (MDR1 P-gp) and MDR-associated protein 1 (MRP1), for translocation of PS. Since
      cyclosporin A (MDR1 P-gp inhibitor) but not MK571 (MRP1 inhibitor) inhibited SAL
      induced PS externalization, it was suggested that MDR1 P-gp is involved in this
      phenomenon. On the other hand, SAL activated both of the ABC transporters for
      efflux of rhodamine123 (MDR1 P-gp substrate, Rho123) and 5-carboxyfluorescein
      diacetate (MRP1 substrate, 5-CFDA) in Raji cells. In contrast, SAL did not
      activate these two transporters in Gb3-negative cell lines, such as K562 and
      doxorubicin-resistant K562 cells, involving not only PS externalization but also
      efflux of Rho123 or 5-CFDA. Since Gb3 and both transporters in Raji cells are
      located in the glycosphingolipid-enriched microdomain (GEM), it is suggested that
      the binding of SAL to Gb3 localized in the GEM specifically induces MDR1 P-gp
      activation in Raji cells.

PMID- 15744066
TI  - The hepatoprotective effect of Bupleurum kaoi, an endemic plant to Taiwan,
      against dimethylnitrosamine-induced hepatic fibrosis in rats.
AB  - In the present study, three materials extracted or isolated from the roots of B.
      kaoi, an endemic plant to Taiwan, were used to be examined the hepatoprotective
      effect against dimethylnitrosamine (DMN)-induced hepatic fibrosis in rats, they
      were water extract (BKW), polysaccharide-enriched fractions (BKP) and saponin
      enriched fractions (BKS). After treated with DMN for 4 weeks, the levels of
      aminotrasferases (GOT, GPT) were significantly elevated in serum, and the levels
      of total protein (TP) and albumin were significantly decreased in serum and liver
      homogenates. Furthermore, the collagen contents were significantly elevated in
      liver homogenates and corresponded to the hepatofibrotic pathological
      examination. As the results showed, treated with groups of BKW, BKP, BKS markedly
      reduced GOT, GPT levels in rats serum. In addition, treated with groups of BKW,
      BKP, BKS markedly raised TP levels in rats serum and liver homogenates.
      Furthermore, treated with groups of BKW, BKP markedly raised albumin levels in
      rats serum and liver homogenates. Treated with groups of BKW, BKP, BKS markedly
      raised interferon-gamma (IFN-gamma) levels in rats serum, where only BKS and
      silymarin markedly raised interkeukin-10 (IL-10) levels in rats serum compared to
      that of DMN treated rats. None of test materials of B. kaoi except silymarin
      reduced the malondialdehyde (MDA) levels, but BKW, BKP markedly raised hepatic
      glutathione (GSH) levels to reveal the activity of anti-lipid peroxidation.
      Otherwise, treated with groups of BKW, BKP, BKS significantly reduced collagen
      contents in rats liver homogenates. In conclusion, B. kaoi demonstrated the anti
      inflammatory and anti-fibrotic activities followed by anti-oxidant activity of
      enhanced GSH production, enhanced the liver cell regeneration and concerned with
      regulations of INF-gamma and IL-10. The ability of hepatoprotective and anti
      fibrotic activities of B. kaoi are higher than B. chinense, a Bupleuri Radix
      imported from China to Taiwan.

PMID- 15744067
TI  - Armeniacae semen extract suppresses lipopolysaccharide-induced expressions of
      cyclooxygenase [correction of cycloosygenase]-2 and inducible nitric oxide
      synthase in mouse BV2 microglial cells.
AB  - Armeniacae semen is the seed of Prunus armeniaca L. var. ansu MAXIM which is
      classified into Rosaceae. In traditional oriental medicine, Armeniacae semen has
      been used for the treatment of pain and inflammatory diseases. In this study, the
      effect of Armeniacae semen extract on lipopolysaccharide-induced inflammation was
      investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), Western
      blot, prostaglandin E2 immunoassay, and nitric oxide detection on mouse BV2
      microglial cells. In the present results, Armeniacae semen extract suppressed
      prostaglandin E2 synthesis and nitric oxide production by inhibiting the
      lipopolysaccharide-stimulated enhancement of cyclooxygenase-2 and inducible
      nitric oxide synthase mRNA expression in BV2 cells. These results show that
      Armeniacae semen exerts anti-inflammatory and analgesic effects probably by
      suppression of cyclooxygenase-2 and inducible nitric oxide synthase expressions.

PMID- 15744068
TI  - Neuroprotective and antioxidant effects of the ethyl acetate fraction prepared
      from Tussilago farfara L.
AB  - The flower buds of Tussilago farfara L. (Compositae) have been traditionally used
      in Oriental medicine for the treatment of bronchitis and asthma. The extract of
      T. farfara was reported to exhibit antiinflammatory actions by inhibiting
      arachidonic acid metabolism and nitric oxide (NO) production in
      lipopolysaccharide-activated macrophages. In the present study, we investigated
      the effects of the ethyl acetate (EA) fraction on various types of neuronal cell
      damage induced in primary cultured rat cortical cells. Its antioxidant activities
      were also evaluated by cell-free bioassays. We found that the EA fraction
      potently inhibited the neuronal damage induced by arachidonic acid. We also found
      that it significantly attenuated the neuronal damage induced by spermine NONOate,
      a stable NO generator. In addition, it inhibited the A(beta(25-35))-induced
      neurotoxicity and glutamate- or N-methyl-D-aspartic acid-induced excitotoxicity.
      It was found that the oxidative neuronal damage induced by H2O2,
      xanthine/xanthine oxidase, or Fe(2+)/ascorbic acid was also inhibited by the EA
      fraction. Furthermore, it was shown to inhibit lipid peroxidation initiated by
      Fe(2+)/ascorbic acid in rat brain homogenates, and scavenge DPPH radicals. This
      is the first demonstration of neuroprotective and antioxidant effects of T.
      farfara. Although complex mechanisms may be involved in the neuroprotective
      actions, T. farfara may be useful for the management of neurodegenerative
      disorders associated with inflammation, A(beta), excitotoxicity, and/or oxidative
      stress.

PMID- 15744069
TI  - Oridonin enhances phagocytosis of UV-irradiated apoptotic U937 cells.
AB  - We previously reported that oridonin, a major component isolated from the plant
      Rabdosia rubescens HEMSL, induced apoptosis in human melanoma A375-S2 and
      cervical cancer HeLa cells. In the present study, oridonin was first evaluated
      for its effect on phagocytosis of apoptotic cells by macrophages. Preincubation
      of human histocytic lymphoma U937 cell-derived macrophages with 2.7 microM
      oridonin significantly augmented phagocytosis of UV-irradiated (2.4 J/cm2, 4 min)
      U937 cells undergoing apoptosis in a dose- and time-dependent manner. However,
      less effect on synthetic fluoresbrite microspheres indicated that enhancement of
      apoptotic U937 cell uptake by oridonin was a selective effect. The oridonin
      augmented phagocytosis was attenuated by anti-human TNFalpha and IL-1beta
      antisera, suggesting that TNFalpha and IL-1beta participate in the phagocytosis
      by oridonin-treated U937 cell-derived macrophages. In addition, the similar
      effect of phagocytosis was observed in oridonin-treated human monocyte-derived
      macrophages at 4 d maturation. Taken together, oridonin facilitates the
      phagocytic activity against apoptotic cells through TNFalpha and IL-1beta
      release, which may be contribute to its antitumor activities.

PMID- 15744070
TI  - Antiallergic, antipyretic, hypoglycemic and hepatoprotective effects of aqueous
      extract of Coronopus didymus Linn.
AB  - The aqueous extract of whole plant of Coronopus didymus LINN (CD) [Family:
      Bracicacea] was screened for antiallergic, antipyretic and hepatoprotective
      effects in rats and hypoglycemic activity in mice. The extract showed significant
      antiallergic, antipyretic, hypoglycemic and hepatoprotective activity at 200 and
      400 mg/kg doses on oral administration. Mechanistically, CD acts as an
      antioxidant as evidenced by its ability to scavenge DPPH and superoxide radicals.
      All the observed activities may be due to the presence of flavonoids, saponins
      and tannins as they are reported to possess a variety of biological activities.

PMID- 15744071
TI  - Increasing effect by simultaneous use of levocabastine and pemirolast on
      experimental allergic conjunctivitis in rats.
AB  - The effect of the simultaneous use of 0.025% levocabastine hydrochloride eye
      drops (levocabastine) and 0.1% pemirolast potassium ophthalmic solution
      (pemirolast) on experimental allergic conjunctivitis in rats was investigated.
      Levocabastine and pemirolast significantly inhibited allergic conjunctivitis
      compared with the control group when separately administered. In addition, the
      simultaneous use of both drugs inhibited allergic conjunctivitis more potently
      than the original activity of levocabastine or pemirolast. Furthermore, the
      simultaneous use of levocabastine and pemirolast also significantly inhibited
      increased vascular permeability induced by antigen compared with levocabastine or
      pemirolast alone, respectively. Levocabastine and pemirolast inhibited histamine
      release from the rat conjunctiva in correlation with a decrease in histamine
      content in tears. When levocabastine and pemirolast were simultaneously applied
      to the eyes, histamine release from the conjunctiva was greater than for the
      original activities of both drugs. Similar to histamine release from the
      conjunctiva, the histamine content in tears induced by the simultaneous use of
      both drugs was significantly decreased compared with levocabastine and pemirolast
      alone, respectively. A potentiating effect induced by the simultaneous use of
      levocabastine and pemirolast may be attributable to the antihistaminic activity
      of levocabastine and histamine release inhibition by levocabastine and
      pemirolast.

PMID- 15744072
TI  - Analysis of the blood level of micafungin involving patients with hematological
      diseases: new findings regarding combination therapy with tacrolimus.
AB  - In 29 patients (40 samples) with hematological diseases who had been treated with
      a candin antifungal agent, micafungin (MCFG), we measured the blood level of MCFG
      by high-performance liquid chromatography (HPLC). There was a correlation between
      the dose and the blood level of MCFG (r = 0.729, p < 0.001). In addition, there
      was a correlation between the total bilirubin level and the C/D value (r = 0.458,
      p < 0.01), which was calculated by dividing the blood level of MCFG by the dose,
      although there was no correlation between creatinine clearance and the C/D value.
      These findings suggest that the dose of MCFG must be regulated in patients with
      biliary stasis-type liver hypofunction. In addition, there was no significant
      difference in the blood level of MCFG between the group in which tacrolimus
      (FK506) was combined with MCFG and the group in which MCFG alone was
      administered. These results suggest that there are no changes in the blood level
      of MCFG even when MCFG is combined with FK506.

PMID- 15744073
TI  - Antioxidant effects of aqueous extracts from dried calyx of Hibiscus sabdariffa
      Linn. (Roselle) in vitro using rat low-density lipoprotein (LDL).
AB  - The present study quantitatively investigated the antioxidant effects of the
      aqueous extracts from dried calyx of Hibiscus sabdariffa LINN. (roselle) in vitro
      using rat low-density lipoprotein (LDL). Formations of the conjugated dienes and
      thiobarbituric acid reactive substances (TBARs) were monitored as markers of the
      early and later stages of the oxidation of LDL, respectively. Thus, we
      demonstrated that the dried calyx extracts of roselle exhibits strong antioxidant
      activity in Cu(2+)-mediated oxidation of LDL (p<0.05) in vitro. The inhibitory
      effect of the extracts on LDL oxidation was dose-dependent at concentrations
      ranging from 0.1 to 5 mg/ml. Moreover, 5 mg/ml of roselle inhibited TBARs
      formation with greater potency than 100 microM of vitamin E. In conclusion, this
      study provides a quantitative insight into the potent antioxidant effect of
      roselle in vitro.

PMID- 15744074
TI  - A short peptide GPIGS promotes proliferation of hair bulb keratinocytes and
      accelerates hair regrowth in mice.
AB  - The aim of this study was to discover a novel agent that promotes hair growth. We
      carried out a screening test in 298 types of conditioned medium (CM) from
      cultures of bacteria by using a hair bulb keratinocyte (HBK) growth assay. As a
      result, we found a HBK growth factor in the CM of Bacillus sp. M18. This HBK
      growth factor was purified by collecting biologically active fractions in three
      steps, including HP-20 batch processing, LH-20 chromatography and C18 reverse
      phase high-pressure liquid chromatography, and identified as a short peptide
      GPIGS. GPIGS increased Akt phosphorylation in HBKs. Moreover, the GPIGS
      stimulated HBK growth was inhibited by the treatment with LY294002, an inhibitor
      of phosphatidylinositol 3-kinase (PI-3K). These results suggest that GPIGS
      promotes HBK growth via the PI-3K/Akt pathway. In addition to in vitro tests,
      GPIGS was found to accelerate hair regrowth in telogen mice. Our results indicate
      that GPIGS is a potential agent to promote hair growth.

PMID- 15744075
TI  - Protective effects of Hippophae rhamnoides L. juice on lead-induced neurotoxicity
      in mice.
AB  - We examined the effect of Hippophae rhamnoides L. (HRL) juice on lead-induced
      memory impairment and neuronal damage in the brains of adult mice. Kunming mice
      were exposed to lead acetate 10 mg/kg body weight for 20 d. Twenty percent and
      40% HRL prevented the lead-induced decrease in step-through latency. In the water
      maze test, the swimming time was lengthened in mice treated with lead acetate,
      but this time was decreased in mice that received 20% and 40% HRL. The
      malondialdehyde (MDA) levels were increased in lead-treated mice, which were
      reduced by 20% and 40% HRL in dose-dependent manner. The activities of
      acetylcholinesterase (AchE) and monoamine oxidase-A and -B were significantly
      increased in the lead-treated group, which were decreased by 40% HRL but not by
      20% HRL. The levels of norepinephrine, serotonin, and 5-hydroxyindole acetic acid
      were decreased significantly in the lead-treated mice, and the decreases were
      antagonized by 40% HRL, except for than in dopamine, but 20% HRL had no effect on
      this change. These data suggest that the different doses of the HRL juice protect
      against the lead acetate-induced deficits in learning and memory and changes in
      neurobiochemical parameters.

PMID- 15744076
TI  - Mechanism-based inhibition of CYP3A4 by constituents of Zingiber aromaticum.
AB  - Sixteen compounds isolated from Zingiber aromaticum and showing concentration
      dependent inhibition with IC50 values less than 100 microM, were analyzed for
      their possibility of time-, concentration-, and NADPH-dependent inhibition of
      CYP3A4 and four were analyzed for CYP2D6. All seven kaempferol glycosides and two
      kaempferol derivatives (4, 5, 8-14) appear to be the mechanism-based inhibitors
      of CYP3A4 enzyme in which the inhibition is irreversible and driven by the
      catalytic process. The other compounds showed no NADPH-dependent inhibition or
      reversible inhibition, and thus do not appear to be mechanism-based inhibitors.
      K(I) values for compounds 4, 5, 8-14 were in the range of 2.21-27.01 microM,
      whereas the k(inact) values were 0.23-0.65 min(-1). Kaempferol-3-O-(2,3,4-tri-O
      acetyl-alpha-L-rhamnopyranoside) (5) was found to be the most potent CYP3A4
      inactivator with K(I) and k(inact) values of 2.21 microM and 0.45 min(-1),
      respectively.

PMID- 15744077
TI  - Enhancing effects of galactosylated dendrimer/alpha-cyclodextrin conjugates on
      gene transfer efficiency.
AB  - To improve in vitro gene transfer efficiency and/or achieve cell-specific gene
      delivery of polyamidoamine (PAMAM) starburst dendrimer (generation 2, G2)
      conjugate with alpha-cyclodextrin (alpha-CDE conjugate (G2)), we prepared alpha
      CDE conjugate bearing galactose (Gal-alpha-CDE conjugates) with the various
      degrees of substitution of the galactose moiety (DSG) as a novel non-viral
      vector. The agarose gel electrophoretic studies revealed that Gal-alpha-CDE
      conjugates formed complexes with plasmid DNA (pDNA) and protected the degradation
      of pDNA by DNase I, but these effects impaired as the DSG value increased.
      Dendrimer and alpha-CDE conjugate exerted pDNA condensation through the
      complexation, but Gal-alpha-CDE conjugates did not. Gal-alpha-CDE conjugate (DSG
      4) was found to have much higher gene transfer activity than dendrimer, alpha-CDE
      conjugate and Gal-alpha-CDE conjugates (DSG 8, 15) in HepG2, NIH3T3 and A549
      cells, which are independent of the expression of the asialoglycoprotein
      receptor. Transfection activity of Gal-alpha-CDE conjugate (DSG 4) was
      insensitive to the existence of competitors (asialofetuin and galactose) and
      serum. In addition, no cytotoxicity after transfection of the complex of pDNA
      with Gal-alpha-CDE conjugate (DSG 4) was observed. These results suggest the
      potential use of Gal-alpha-CDE conjugate (DSG 4) as a non-viral vector in various
      cells.

PMID- 15744078
TI  - Characterization of graphislactone A as the antioxidant and free radical
      scavenging substance from the culture of Cephalosporium sp. IFB-E001, an
      endophytic fungus in Trachelospermum jasminoides.
AB  - The extracts derived from cultures of 1626 endophytic strains harbored in
      Trachelospermum jasminoides were assayed for more potent antioxidant and/or free
      radical-scavenging agents. The free radical-scavenging assessment was carried out
      using l,l-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical assays, and the
      antioxidant actions on linoleic acid and human low-density lipoprotein (LDL)
      models. After extensive spectroscopic analyses, graphislactone A was
      characterized as the most bioactive secondary metabolite of endophytic
      Cephalosporium sp. IFB-E001 with its free radical-scavenging (in a dose-dependent
      manner) and antioxidant activities ascertained in vitro to be stronger than those
      of butylated hydroxytoluene (BHT) and ascorbic acid, the two positive references
      coassayed in the study. From the demonstrated efficacy of graphislactone A in
      preventing and protecting against oxidative injury, it can be predicted that this
      metabolite could be a potential agent in the management of oxidative damage
      initiated diseases.

PMID- 15744079
TI  - Effect of aminated gelatin on the nasal absorption of insulin in rats.
AB  - Absorption enhancers, which increase the permeability of drugs through epithelial
      membranes without damaging them, are especially useful for intranasal
      administration of peptide drugs. In this study, aminated gelatins, candidate
      enhancers, having different numbers of amino groups were prepared from gelatin (H
      gelatin, isoelectric point = 9.0, MW 100 kDa) and a partial gelatin hydrolysate
      (L-gelatin, isoelectric point = 8.0, MW 5 kDa), and the enhancing effects on the
      nasal absorption of insulin, used as a model peptide drug, and 5(6)
      carboxyfluorescein (CF), a paracellular marker, were examined in rats. The
      enhancing effect on insulin and CF depends on the MW and number of amino groups.
      A high correlation between the enhancing effects on insulin and CF was observed
      and this suggests that an increase in the paracellular permeability is the
      mechanism governing the nasal absorption-enhancement of aminated gelatins, at
      least as far as insulin and CF are concerned. The enhancing mechanism might be
      shared with other cationic polymers having absorption-enhancing effects.

PMID- 15744080
TI  - Inhibition of eosinophil survival by a selective inhibitor of phosphodiesterase 4
      via the induction of apoptosis.
AB  - Selective inhibitors of phosphodiesterases (PDEs) have been suggested to have
      anti-inflammatory effects on bronchial asthma through the inhibition of
      chemotaxis, adhesion, degranulation, the respiratory burst, and survival
      prolongation of eosinophils. However, the mechanisms by which these agents
      inhibit eosinophil survival remain unclear. We therefore investigated the
      possible mechanisms of inhibitory effects of selective inhibitors of PDE 3
      (cilostazol) and PDE 4 (rolipram) on granulocyte-macrophage colony-stimulating
      factor (GM-CSF)-mediated eosinophil survival. Purified blood eosinophils were
      cultured with medium alone or GM-CSF (0.01 ng/ml) in the presence or absence of
      the agents for up to 6 d. DNA was extracted from freshly isolated eosinophils and
      eosinophils cultured for 2 d with medium alone, GM-CSF, or GM-CSF in the presence
      of the agents, and analyzed using agarose gel electrophoresis. The presence of
      rolipram (10(-4), 10(-5), 10(-6) M), but not cilostazol, significantly inhibited
      eosinophil survival at days 2, 4, and 6. A laddering pattern was observed in the
      DNA of eosinophils cultured with medium alone and with GM-CSF in the presence of
      rolipram. The results reveal that selective PDE 4 inhibitors inhibit GM-CSF
      mediated eosinophil survival through the induction of apoptosis.

PMID- 15744081
TI  - In vivo mutagenicities of damaged nucleotides produced by nitric oxide and
      ionizing radiation.
AB  - To evaluate the in vivo mutagenicities of damaged DNA precursors
      (deoxyribonucleoside 5'-triphosphates) produced by exposure to nitric oxide (NO)
      and ionizing radiation, five damaged deoxyribonucleotides (deoxyxanthosine
      triphosphate, deoxyoxanosine triphosphate, dITP, dUTP, and 8-hydroxy-dATP) were
      introduced into competent Escherichia coli cells. Their mutagenic potentials were
      assayed using the chromosomal rpoB gene as a mutagenesis target. In contrast to 8
      hydroxy-dGTP and 2-hydroxy-dATP, which were examined in an earlier study, none of
      these damaged deoxyribonucleotides significantly increased the rpoB mutant
      frequency. These results suggest that these five damaged deoxyribonucleotides are
      weakly mutagenic in vivo if at all. Thus their contributions to mutations induced
      by NO and ionizing radiation may be small.

PMID- 15744082
TI  - Araloside A, an antiulcer constituent from the root bark of Aralia elata.
AB  - Araloside A, a potent inhibitor of gastric lesion and ulcer formation in rats,
      was isolated from the root bark of Aralia elata through a bioassay-guided
      separation procedure. The compound exhibited significant reduction of HCl.ethanol
      induced gastric lesions and aspirin-induced gastric ulcers at oral doses of 50
      and 100 mg/kg, respectively. These activities are comparable to those of
      cimetidine.

PMID- 15744083
TI  - Inhibitory effects of naringenin on tumor growth in human cancer cell lines and
      sarcoma S-180-implanted mice.
AB  - We have investigated the effect of naringenin (NGEN) on tumor growth in various
      human cancer cell lines and sarcoma S-180-implanted mice. NGEN showed
      cytotoxicity in cell lines derived from cancer of the breast (MCF-7, MDA-MB-231),
      stomach (KATOIII, MKN-7), liver (HepG2, Hep3B, Huh7), cervix (Hela, Hela-TG),
      pancreas (PK-1), and colon (Caco-2) as well as leukemia (HL-60, NALM-6, Jurkat,
      U937). NGEN-induced cytotoxicity was low in Caco-2 and high in leukemia cells
      compared to other cell lines. NGEN dose-dependently induced apoptosis, with
      hypodiploid cells detected in both Caco-2 and HL-60 by flow cytometric analysis.
      In vivo, NGEN inhibited tumor growth in sarcoma S-180-implanted mice, following
      intraperitoneal or peroral injection once a day for 5 d. Naringin (NG) also
      inhibited tumor growth by peroral injection but not intraperitoneal injection.
      NGEN, one of the most abundant flavonoids in citrus fruits, may have a
      potentially useful inhibitory effect on tumor growth.

PMID- 15744084
TI  - Hepatoprotective effects of irisolidone on tert-butyl hyperoxide-induced liver
      injury.
AB  - To clarify the hepatoprotective effects of kakkalide and its metabolite
      irisolidone by human fecal microflora, their effects on tert-butyl hydroperoxide
      (t-BHP)-injured HepG2 cells and mice were investigated. Irisolidone protected
      HepG2 cells against cytotoxicity induced by t-BHP. However, kakkalide did not
      protect cytotoxicity. When kakkalide 100 mg/kg was orally administered to mice
      injured by t-BHP, it significantly inhibited the increase in plasma alanine
      aminotransferase and aspartate aminotransferase activities by 84% and 85% of t
      BHP-treated control group, respectively. The inhibitory effect of kakkalide is
      much more potent than that of silybin, a hepatoprotective agent. However,
      intraperitoneally administered kakkalide did not exhibit hepatoprotective
      activity. When irisolidone was intraperitoneally administered to mice, it
      exhibited potent hepatoprotective activity. Based on these findings, irisolidone
      can be hepatoprotective and kakkalide may be a prodrug transformed to
      irisolidone.

PMID- 15744086
TI  - Evaluation of the estrogenic activity of Leguminosae plants.
AB  - The plant extracts of the Leguminosae family were screened for their estrogenic
      activity with the Ishikawa cell system. Of the tested plants, Desmodium
      oxyphyllum, Dunbaria villosa, Kummerowia striata, Lespedeza bicolor, Maackia
      amurensis, Maackia fauriei, Pueraria thunbergiana, and Sophora flavescens were
      highly estrogenic with EC50 values of less than 10 microg/ml.

PMID- 15744085
TI  - Hepatoprotective activity of the constituents in Swertia pseudochinensis.
AB  - A new xanthone derivative was isolated together with other 13 known constituents
      from a Chinese natural medicine, Swertia pseudochinensis HARA. Their structures
      were determined based on the spectral and chemical evidences. Furthermore,
      respective hexane, ethyl acetate, 1-BuOH, MeOH and water extracts of S.
      pseudochinensis, and purified compounds were respectively evaluated for their
      hepatoprotective activities against hepatocyte injury induced by CCl4. All the
      extracts and isolated compounds exhibited significant hepatoprotective activities
      at a dose showing no hepatoxicity.

PMID- 15744087
TI  - Berberine synergy with amphotericin B against disseminated candidiasis in mice.
AB  - In present study, we investigated the synergic effect of berberine against
      disseminated candidiasis caused by the pathogenic fungus, Candida albicans.
      Berberine inhibited the growth of C. albicans under in-vitro condition. The broth
      susceptibility revealed the synergic effect of berberine with amphotericin B (Amp
      B). To confirm these results under the in-vivo condition, the effect was examined
      in mice against disseminated candidiasis. Results showed mice that were given
      diluent (negative control), Amp B (0.5 mg/kg of body weight), or berberine (1
      mg/kg of body weight) had mean survival times (MST) of approximately 12, 14, and
      17 d, respectively. On the contrary, mice that were treated using a combination
      of the two agents at the same concentrations resulted in a MST value of 36 d,
      surviving at an average of 22 d longer than the mice group treated only with the
      Amp B. This MST value was almost same as MST value from the mice that were given
      four times the Amp B dose. These data indicate that the combination of Amp B and
      berberine could reduce approximately 75% of the Amp B dose, implying that
      berberine indeed has synergy with Amp B against the disseminated disease.

PMID- 15744088
TI  - Pharmacokinetics of chitobiose and chitotriose administered intravenously or
      orally to rats.
AB  - Chitooligosaccharides have attracted much attention as new biomedical materials.
      The biologic availability of each of these chitooligosaccharides, however, has
      not yet been studied. In the present study, we found that chitobiose and
      chitotriose appeared in the blood of rats with maximum plasma concentrations at
      around 1 h after administration when given orally at a dose of 30 mg/kg. However,
      chitotetraose and chitopentaose did not appear in the blood when given at a dose
      of 300 mg/kg. Pharmacokinetic analysis of chitobiose and chitotriose after
      intravenous administration at 100 mg/kg revealed that both sugars were eliminated
      from the body following a one-compartment model and that the former relative to
      the latter was higher for both the total body clearance (224+/-43 vs. 155+/-26
      ml/h/kg) and the distribution volume (107+/-15 vs. 65+/-9 ml/kg). The absolute
      oral bioavailability of chitobiose was higher than that of chitotriose at all
      doses (30, 100, and 300 mg/kg) examined. The first-order absorption rate
      constants for chitobiose and chitotriose at all doses were less than 1.0 h(-1)
      and smaller than the elimination rate constants (2.2+/-0.3, 2.7+/-0.1 h(-1),
      respectively). The absorption was slow, resulting in flip-flop kinetics. This
      study indicates that among various chitooligosaccharides, only chitobiose and
      chitotriose can be appreciably absorbed from the gastrointestinal tract.

PMID- 15744089
TI  - Inhibitory effects of amino-acid fluids on drug binding to site II of human serum
      albumin in vitro.
AB  - The effects of amino-acid fluids on ligand binding to human serum albumin (HSA)
      were investigated by fluorescence and ultrafiltration techniques. Warfarin and
      dansylsarcosine were used as the site marker fluorescence probes for site I and
      site II of HSA, respectively. Amino-acid fluids specifically decreased the
      fluorescence intensity induced by dansylsarcosine-HSA binding without any effects
      on that induced by warfarin-HSA binding. The ultrafiltration technique clarified
      that the free fraction of the site II drug, diazepam, in human serum was
      increased in the presence of amino-acid fluids, while no effect was observed in
      the free fraction of the site I drug, warfarin. The potencies of the effect on
      binding to site II, observed by fluorescence and ultrafiltration techniques,
      correlated well with the L-tryptophan contents in amino-acid fluids or with those
      in L-tryptophan solutions. Based on the comparison between the effects of amino
      acid fluids and L-tryptophan solutions, we confirmed that L-tryptophan in amino
      acid fluids specifically inhibits drug binding to site II of HSA.

PMID- 15744090
TI  - Glycerol absorption by Na+-dependent carrier-mediated transport in the closed
      loop of the rat small intestine.
AB  - The absorption of glycerol was examined using the closed loop of the rat small
      intestine in situ to clarify the transport mechanism. The absorption of glycerol,
      evaluated by its disappearance from the intestinal lumen, was saturable and
      reduced under the Na(+)-free conditions, suggesting the involvement of an Na(+)
      dependent carrier-mediated transport system. Furthermore, glycerol absorption was
      selectively inhibited by several alcohols, among which 1,3-propanediol caused the
      greatest inhibition, and also by glycerol-3-phosphate and voglibose, which are
      alcohol-related compounds analogous to glycerol. Several other compounds that did
      not inhibit glycerol absorption included D-glucose and L-ascorbate, which are
      known to be transported by specific carriers. Therefore, the carriers for these
      two compounds do not seem to be involved in glycerol absorption. It is likely
      that the carrier-mediated transport system involved in glycerol absorption is
      specific to glycerol and, possibly, some analogous compounds with hydroxyl
      groups. Thus, the present study has provided in situ evidence for the presence of
      an Na(+)-dependent carrier-mediated transport system for glycerol in the rat
      small intestine. It would be interesting to examine the possibility that the
      carrier-mediated glycerol transport system could be involved in drug absorption
      and also that it could be used for oral drug delivery.

PMID- 15744091
TI  - Pharmacokinetic behavior of micafungin in rats with carbon tetrachloride-induced
      acute hepatic failure.
AB  - We examined the pharmacokinetic behavior of micafungin, a novel antifungal agent,
      in rats receiving carbon tetrachloride (CCl4) at a single dose of 2.5 ml/kg.
      There was no significant change in the total clearance (CL(tot)) in CCl4-treated
      rats, while the steady-state volume of distribution (Vd(ss)) was significantly
      increased by CCl4 treatment. Alteration in the serum unbound fraction of
      micafungin after CCl4 treatment was unlikely in light of the serum albumin,
      bilirubin, creatinine, and urea nitrogen. The increased Vd(ss) was attributable
      to augmentation in the accessibility of micafungin to peripheral tissue without
      impairment of the intrinsic clearance, because slight enhancement of the tissue
      distribution of micafungin was confirmed following CCl4 treatment.

PMID- 15744092
TI  - Uptake of pullulan in cultured rat liver parenchymal cells.
AB  - Uptake of pullulan, including a binding process followed by internalization, was
      examined in cultured rat liver parenchymal cells. A tyramine derivative of
      pullulan was labeled with [125I]iodine and used as a ligand. Pullulan bound to
      the cell surface was released by EDTA treatment, indicating that pullulan binding
      requires Ca2+ and a contribution from the asialoglycoprotein receptor. Binding of
      pullulan reached a steady state and internalization represented a biphasic mode,
      which included first- and zero-order processes in the initial stage and after 20
      min incubation, respectively. The uptake of pullulan could be estimated by a
      similar model for intracellular disposition of asialofetuin. Kinetic parameters
      of pullulan constituting both binding and internalization were below those found
      for asialofetuin. These results suggest that pullulan is taken up by liver
      parenchymal cells via the asialoglycoprotein receptor; however, uptake
      availability is lower than that of asialofetuin.

PMID- 15744093
TI  - Enhancement of all-trans retinoic acid-induced HL-60 cell differentiation by
      thalidomide and its metabolites.
AB  - Thalidomide (Thal: 1) and its two metabolites, 5-hydroxythalidomide (5-HT: 2) and
      N-hydroxythalidomide (N-HT: 3), showed an enhancing effect on all-trans retinoic
      acid (ATRA)-induced HL-60 cell differentiation. 5-HT and N-HT showed tubulin
      polymerization-inhibiting activity, but thalidomide did not.

PMID- 15744094
TI  - Lipoxygenase inhibiting constituents from Indigofera hetrantha.
AB  - A lignan and two acylphloroglucinols have been isolated from the ethyl acetate
      soluble fraction of the whole plant of Indigofera hetrantha. Their structures
      have been assigned on the basis of spectral analysis including 1D and 2D NMR
      techniques. Compounds 1-3 displayed promising inhibitory potential against enzyme
      lipoxygenase in concentration-dependent manner.

PMID- 15744095
TI  - mCPBA oxidation of acetyllycoctonine and its new products.
AB  - Treatment of a lycoctonine-type alkaloid acetyllycoctonine (4) with mCPBA at room
      temperature led to acetyllycoctonine N-oxide (5) as the major product together
      with other interesting compounds 6-12 as the minor products, which were derived
      from oxidation involving the nitrogen atom and Cope elimination as well as
      Polonovski-like fragmentation. All of those new compounds (5-12) were fully
      characterized.

PMID- 15744096
TI  - Decrease in skin permeation and antibacterial effect of parabens by a polymeric
      additive, poly(2-methacryloyloxyethyl phosphorylcholine-co-butylmetacrylate).
AB  - The inhibitory effect of poly(2-methacryloyloxyethyl phosphorylcholine-co
      butylmetacrylate) (PMB) on the in vitro skin permeation of p-hydroxybenzoic acid
      and its esters (parabens; methylparaben, ethylparaben, n-propylparaben and n
      butylparaben) as model compounds was evaluated. Solubility of the parabens in
      distilled water was increased by addition of PMB, and the increasing ratio was
      dependent on the concentration of PMB. The increment of the ratio was more marked
      in lipophilic parabens than hydrophilic ones. Skin permeability of parabens from
      their aqueous suspensions was decreased by addition of PMB, and the decreasing
      ratio was dependent on the PMB concentration. Then, antibacterial effect of
      parabens of their aqueous solutions was determined with and without PMB by
      measuring minimum inhibitory concentration (MIC) against E. coli and S. aureus.
      As results, MIC and antibacterial effect were increased and decreased,
      respectively, by addition of PMB. The contribution of PMB was more marked in
      butylparaben than methylparaben. These decreases in skin permeation and
      antibacterial effect of parabens by PMB are probably due to a higher solubility
      in water and a lower partition to the skin and bacterial membranes of parabens by
      addition of PMB.

PMID- 15744097
TI  - Influence of medium and temperature on the hydrolysis kinetics of propacetamol
      hydrochloride: determination using derivative spectrophotometry.
AB  - Propacetamol hydrochloride (PRO) is a water-soluble prodrug of paracetamol (PA)
      which can be parenterally administered as analgesic for the treatment of
      postoperative pain, acute trauma, and gastric and/or intestinal disorders where
      oral administration is not possible. In these circumstances, PRO can be
      administered in physiologic or glucose solutions since it is rapidly and
      quantitatively hydrolyzed into PA by plasma estearases. We have studied the
      degradation kinetics of PRO in 5% glucose and 0.9% saline solutions at 4 degrees
      C and 25 degrees C (storage and room temperatures, respectively). The analytic
      technique used to determine PRO and PA quantitatively was first-derivative
      spectrophotometry. The degradation process of PRO can be best fitted to a second
      order kinetics with independence of the medium used (saline or glucose solution).
      The hydrolysis kinetics of PRO conversion into PA depends on the temperature but
      not on the assay medium (saline or glucose solution). The degradation rate
      constants obtained for PRO were approximately 4.5 times higher at 25 degrees C
      than at 4 degrees C. The values of t(90%) for PRO were 3.17 h and 3.61 h at 25
      degrees C, and 13.42 h and 12.36 h at 4 degrees C when the tests were performed
      in 5% glucose and 0.9% saline solutions, respectively.

PMID- 15744098
TI  - Determination of in vitro antioxidant and radical scavenging activities of
      propofol.
AB  - Propofol (2,6-diisopropylphenol) is a hypnotic intravenous agent with in vivo
      antioxidant properties. This study was undertaken to examine the in vitro
      antioxidant activity of propofol using different antioxidant tests including by
      1,1-diphenyl-2-picryl-hydrazil (DPPH.) radical scavenging, metal chelating,
      hydrogen peroxide scavenging, superoxide anion radical scavenging, reducing power
      and total antioxidant activities. At the concentrations of 25, 50, and 75
      microg/ml, propofol exhibited 97.7, 98.6 and 100% inhibition on peroxidation of
      linoleic acid emulsion, respectively. On the other hand, at the 75 microg/ml
      concentration of standard antioxidants such as butylated hydroxyanisole (BHA),
      butylated hydroxytoluene (BHT) and alpha-tocopherol exhibited 88.7, 94.5, and
      70.4% inhibition on peroxidation of linoleic acid emulsion, respectively. In
      addition, at same concentrations, propofol was shown that it had effective
      reducing power, DPPH. free radical scavenging, superoxide anion radical
      scavenging, hydrogen peroxide scavenging and metal chelating activities. These
      various antioxidant activities were compared to standard antioxidants such as
      BHA, BHT and alpha-tocopherol. These results indicate that propofol prevents
      lipid peroxidation and radicalic chain reactions. At the same time, propofol
      revealed more effective antioxidant capacity than BHA, BHT and alpha-tocopherol.

PMID- 15744099
TI  - Five new diterpenoids from the bark of Taiwania cryptomerioides.
AB  - Five new diterpenoids, 11-hydroxyabieta-8,11,13-trien-7-one (1), 11,12,14
      trihydroxyabieta-8,11,13-trien-7-one (2), 6beta,7alpha-diacetoxyroyleanone (3),
      7beta-hydroxymanoyl oxide (4), and 9alpha-hydroxyisopimara-8(14),15-dien-7-one
      (5) were obtained from the bark of Taiwania cryptomerioides. The structures of
      the new compounds 1-5 were elucidated on the basis of spectral analysis and
      chemical evidence.

PMID- 15744100
TI  - Modeling the entrainer effects on solubility of solutes in supercritical carbon
      dioxide.
AB  - Applicability of a previously published equation for calculating the solubility
      of solutes in supercritical carbon dioxide was extended to calculate the
      solubility in entrained supercritical carbon dioxide employing 42 experimental
      data sets collected from the literature. The accuracy of the proposed model was
      evaluated by calculating both the average absolute relative deviation and the
      individual absolute relative deviation. The proposed model showed superiority to
      a previously published similar model, from both correlation and prediction points
      of view.

PMID- 15744101
TI  - Cytotoxic diterpenoids from Vietnamese medicinal plant Croton tonkinensis GAGNEP.
AB  - Six new ent-kaurane-type diterpenoids were isolated from the leaves of the
      endemic Vietnamese medicinal plant Croton tonkinensis GAGNEP. (Euphorbiaceae)
      together with three known ent-11alpha-acetoxy-7beta,14alpha-dihydroxykaur-16-en
      15-one (1), ent-kaur-16-en-15-one 18-oic acid (5) and ent-18-hydroxykaur-16-ene
      (7). Their structures were determined by spectroscopic analyses to be ent-7beta
      acetoxy-11alpha-hydroxykaur-16-en-15-one (2), ent-18-acetoxy-11alpha-hydroxykaur
      16-en-15-one (3), ent-11alpha-acetoxykaur-16-en-18-oic acid (4), ent-15alpha,18
      dihydroxykaur-16-ene (6), ent-11alpha,18-diacetoxy-7beta-hydroxykaur-16-en-15-one
      (8), and ent-(16S)-1alpha,14alpha-diacetoxy-7beta-hydroxy-17-methoxykauran-15-one
      (14). ent-Kaurane-type diterpenoids from Croton tonkinensis 2-4, 6, and 9-13,
      were tested for toxicity in the brine shrimp lethality assay. Compounds 9, 10,
      and 12 demonstrated significant activity, compounds 2, 3, 6, and 11 showed weak
      activity, and compounds 4 and 13 were inactive.

PMID- 15744102
TI  - Effect of freezing rate on physical stability of lyophilized cationic liposomes.
AB  - Factors affecting the storage stability of lyophilized cationic liposomes were
      investigated using liposomes prepared with various excipients and by different
      freezing rates, either quick freezing (freezing by immersion into liquid
      nitrogen) or slow freezing (cooling to -50 degrees C at a rate of -10 degrees
      C/h). Increases in the particle size of cationic liposomes observed during freeze
      drying were inhibited by the addition of sucrose, trehalose and sucrose-dextran
      mixtures (1 : 1 and 2 : 1 by weight). The storage instability of the
      formulations, as indicated by changes in particle size, was affected by their
      glass transition temperature (T(g)). Addition of high-T(g) excipients resulted in
      smaller increases in the particle size, indicating improvement of storage
      stability. The storage stability of cationic liposome formulations was also
      affected by freezing rate. Formulations prepared by slow freezing exhibited
      better stability. Longer shear relaxation times were observed for formulations
      prepared by slow freezing compared with those prepared by quick freezing. This
      indicates that formulations prepared by slow freezing have a lower matrix
      mobility, which may result in better storage stability. T(g) or (1)H-NMR
      relaxation measurements could not detect differences in matrix mobility between
      formulations prepared by different freezing rates. Shear relaxation measurements
      seem to be a useful method for evaluating the storage stability of cationic
      liposome formulations.

PMID- 15744103
TI  - Flavonoids that mimic human ligands from the whole plants of Euphorbia lunulata.
AB  - In our investigation of a cell proliferation-based screening assay using human
      ligand-dependent cell lines for medicinal herbal extracts, the acetone extract of
      the whole plants of Euphorbia lunulata (EL) was observed for its proliferation
      activity for insulin- and interleukin-10 (IL-10)-dependent cell lines.
      Fractionation of the active extract led to the isolation of one new flavonoid
      galactoside, quercetin 3-O-(2'',3''-digalloyl)-beta-D-galactopyranoside (1), and
      four known ones, quercetin 3-O-(2''-galloyl)-beta-D-galactopyranoside (2),
      hyperin (3), quercetin (4), and gallic acid (5). Compounds 1 and 2 showed insulin
      like activity. Compounds 4 and 5 showed IL-10-like activity. This is the first
      report of these activities of EL, and 1 and 2 will become the seed compounds for
      the development of a nonpeptidyl insulin substitutional medicine. Compounds 4 and
      5 support the pharmacological use of EL, which has been employed as an herbal
      medicine for the treatment of bronchial asthma.

PMID- 15744104
TI  - Pregnane-type steroids from the inedible mushroom Thelephora terrestris.
AB  - Chromatographic fractionation of the methanol extract of fruiting bodies of the
      inedible Japanese mushroom Thelephora terrestris (Thelephoraceae) has led to the
      isolation and characterization of two unusual new pregnane-type steroids,
      2beta,3alpha-dihydroxypregna-4,7,16-trien-12,20-dione (2) and 1alpha,2beta,3alpha
      trihydroxypregna-4,7,16-trien-12,20-dione (3) named terresterones A and B (2, 3),
      as well as the previously known compound stizophyllin, now assigned as
      2beta,3alpha,12beta-trihydroxypregna-4,7,16-trien-20-one (1). Elucidation of
      their structures and the revision of the stereochemical assignment of
      stizophyllin were achieved by means of extensive 1D and 2D NMR, UV, CD, IR, MS
      and molecular modeling experiments. This paper presents the first report on the
      isolation of true pregnane-type steroids from the Fungi kingdom.

PMID- 15744105
TI  - Synthesis of N3-substituted uridine and related pyrimidine nucleosides and their
      antinociceptive effects in mice.
AB  - Seventy eight N(3)-substituted derivatives of uridine (1), thymidine (2), 2'
      deoxyuridine (3), 6-azauridine (4), 2',3'-O-isopropylideneuridine (5), and
      arabinofuranosyluracil (6) were synthesized and their antinociceptive effects
      were evaluated. N(3)-(2',4'-Dimethoxyphenacyl)uridine (1l), N(3)-(2',4'
      dimethoxyphenacyl)2'-deoxyuridine (3l), and N(3)-(2',5'
      dimethoxyphenacyl)arabinofuranosyluracil (6m) possessed 93, 86, and 82% of the
      antinociceptive effects tested by hot plate, respectively. The antinociceptive
      effects of three derivatives were 5.8, 5.4, and 5.1-folds of the effect of N(3)
      phenacyluridine (1h) (16%), respectively. The structure-activity relationship of
      N(3)-substituted pyrimidine nucleosides was also discussed.

PMID- 15744106
TI  - Determination of honokiol and magnolol by micro HPLC with electrochemical
      detection and its application to the distribution analysis in branches and leaves
      of Magnolia obovata.
AB  - A simple and sensitive method has been developed for determining honokiol and
      magnolol in fresh Magnolia obovata (M. obovata) by micro high-performance liquid
      chromatography with electrochemical detection (microHPLC-ECD). Chromatography was
      performed using a Capcell Pak C-18 UG 120 microbore octadecylsilica (ODS) column,
      methanol-water-phosphoric acid (65 : 35 : 0.5, v/v/v), as a mobile phase and
      applied potential at +0.8 V vs. Ag/AgCl. Peak heights were found linearly related
      to the amounts of honokiol and magnolol injected from 0.67 pg to 2.0 ng
      (r>0.999). The detection limits (S/N=3) were 0.13 pg, respectively. Honokiol and
      magnolol of 0.27 ng were detected with relative standard deviation (RSD) of 0.73
      and 1.17% (n=5), respectively. Honokiol and magnolol in Magnolia Bark of the
      Japanese Pharmacopoeia were extracted with 70% methanol, diluted with a mobile
      phase, and injected into the microHPLC-ECD for determination. Recoveries of
      honokiol and magnolol in Magnolia Bark exceeded 98.7% with RSD, less than 0.93%
      (n=5). Determination of the distributions of honokiol and magnolol in bark,
      phloem, wood, leaf blades, and petioles of fresh M. obovata were made using
      weight samples of 40-238 mg. This method is useful to determine honokiol and
      magnolol in M. obovata, which is a candidate for crude magnolia bark for
      traditional Japanese herbal medicines.

PMID- 15744107
TI  - Effect of initial concentration on stability of panipenem in aqueous solution.
AB  - The effect of initial panipenem (CAS No. 87726-17-8) concentration on its
      degradation in an aqueous solution was investigated. The degradation of panipenem
      followed pseudo-first-order kinetics at all the pH values tested. However, in an
      acidic solution, the degradation rate increased with the initial panipenem
      concentration. On the other hand, in an alkaline solution, the degradation rate
      was not affected by its initial concentration. In an acidic solution, the plots
      of the first-order rate constants versus initial panipenem concentrations showed
      a linear relationship. Theoretically, the first-order rate constant is
      independent of the initial concentration, and therefore, the results suggested
      unusualness. We investigated the results obtained under acidic conditions in
      detail to find a very complex reaction mechanism: panipenem and its degradation
      products are factors causing the unusual increase in the degradation rate.
      Moreover, it was shown that the dissociation of the carboxyl group played an
      important role in the degradation of panipenem.

PMID- 15744108
TI  - New cis-clerodane diterpenoids from Croton schiedeanus.
AB  - The acid fraction of extracts from the aerial part of Croton schiedeanus afforded
      six cis-clerodane type diterpenoids. Two of them (1 and 4) are new natural
      compounds. Structural elucidation was achieved on the basis of their spectral
      data.

PMID- 15744109
TI  - A new unsaturated glycoglycerolipid from a cultured marine dinoflagellate
      Amphidinium carterae.
AB  - From the cultured marine dinoflagellate Amphidinium carterae, a new unsaturated
      glycoglycerolipid (2S)-1,2-O-6,9,12,15-dioctadecatetraenoyl-3-O-[alpha-D
      galactopyranosyl-(1''''-->6''')-O-beta-D-galactopyranosyl]-glycerol (1), has been
      isolated together with two known saturated ones, (2S)-1,2-distearoyl-3-O-(6
      sulpho-alpha-D-quinovopyranosyl)-glycerol (2) and (2S)-1-stearoyl-3-O-(6-sulpho
      alpha-D-quinovopyranosyl)-glycerol (3). Their structures were elucidated on the
      basis of chemical and spectral data.

PMID- 15744111
TI  - Longicalycinin A, a new cytotoxic cyclic peptide from Dianthus superbus var.
      longicalycinus (MAXIM.) WILL.
AB  - A new cyclic peptide, longicalycinin A (1), and six known compounds, vaccaroside
      A, dianoside A, dianoside G, 3-(4-hydroxy-3-methoxy-phenyl)propionic acid methyl
      ester, p-hydroxybenzoic acid, and p-hydroxybenzaldehyde were isolated from the
      MeOH extract of Dianthus superbus var. longicalycinus. The amino acid sequences
      of 1 was elucidated as cyclo(Gly(1)-Phe(2)-Tyr(3)-Pro(4)-Phe(5)-) on the basis of
      ESI tandem mass fragmentation analysis, chemical evidence, and extensive 2D NMR
      methods. Furthermore, compound 1 showed cytotoxicity to Hep G2 cancer cell line.

PMID- 15744110
TI  - Constituents of Zingiber aromaticum and their CYP3A4 and CYP2D6 inhibitory
      activity.
AB  - A new sesquiterpene 2,9-humuladien-6-ol-8-one (1) was isolated from methanol
      extract of Zingiber aromaticum, along with 15 known compounds. The structures of
      the isolated compounds were elucidated on the basis of spectroscopic analyses.
      The isolated compounds were tested for their inhibitory activity on the
      metabolism mediated by cytochrome P450 3A4 (CYP3A4) and CYP2D6.

PMID- 15744112
TI  - Ellagitannins and lignan glycosides from Balanophora japonica (Balanophoraceae).
AB  - Three new ellagitannins named balanophotannins A-C having a 1,1'-(3,3',4,4'
      tetrahydroxy)dibenzofurandicarboxyl group in their molecules and four known
      lignan glycosides were isolated from the extracts of fresh aboveground and
      underground parts of a medicinal parasitic plant Balanophora japonica
      (Balanophoraceae). Their structures were elucidated on the basis of spectral and
      chemical evidence. Chemotaxonomic significance of the known lignan glycosides in
      Balanophora japonica was discussed.

PMID- 15744113
TI  - An antibacterial biphenyl derivative from Garcinia bancana MIQ.
AB  - From the methanol extract of the twigs and leaves of Garcinia bancana MIQ., one
      new biphenyl derivative (1), was isolated and characterized along with nine known
      compounds; garcinol, isogarcinol, (-)-mellein, 8-hydroxy-6-methoxy-3-n
      pentylisocoumarin, blumenol C O-beta-D-glucoside, quercetin 3-O-alpha-L
      rhamnoside, kaemferol 3-O-alpha-L-rhamnoside, lupeol and stigmasterol. Their
      structures were determined by analysis of 1D and 2D NMR data and comparison of
      spectral data and physical data with those previously reported. The antibacterial
      activity against methicillin-resistant Staphylococcus aureus was evaluated.
      Garcinol showed the lowest minimum inhibition concentration (MIC) at 16 microg/ml
      while compound 1 exhibited weaker activity with MIC value of 64 microg/ml.

PMID- 15744114
TI  - Antioxidant activity of propofol and related monomeric and dimeric compounds.
AB  - This study was carried out to investigate the antioxidant activity of propofol
      (2,6-diisopropylphenol) and its related compounds, butylated hydroxyanisole
      (BHA), 2,6-dimethylphenol, 2,6-di-t-butylphenol, and their dimeric compounds. The
      degree of antioxidant activity was evaluated based on the degree of peroxidation
      induced with Fe-ascorbic acid in egg phosphatidylcholine through the
      determination of thiobarbituric acid-reactive substances (TBARS) formed during
      peroxidation. Their antioxidant activities were in the order of dipropofol>di(2,6
      di-t-butylphenol)>diBHA>di(2,6-dimethylphenol). Dipropofol, a dimeric compound of
      propofol, showed the highest antioxidant activities. Dimeric compounds had higher
      activities than monomeric compounds, and the 1,1-diphenyl-p-picryhydrazyl
      trapping ability of dimeric compounds was also greater than those of monomeric
      compounds (4-10-fold). These results suggest that dimeric phenols may increase
      their antioxidant activities along with increments in the conjugation system and
      play a inhibitory role in the propagation of free radical chain reactions.

PMID- 15744115
TI  - Quantitative analysis of camptothecin derivatives in Nothapodytes foetida using
      1H-NMR method.
AB  - A quantitative analysis using (1)H-NMR has been developed for the determination
      of camptothecin derivatives and trigonelline in Nothapodytes foetida root, stems
      and leaves. In the region of delta 9.5-5.5, the signals of H-7 of camptothecin
      (1), H-10 of 9-methoxycamptothecin (2), H-19 of pumiloside (3) and H-2 of
      trigonelline (4), were well separated from each other in DMSO-d(6). The quantity
      of the compounds was calculated by the ratio of the intensity of each compound to
      the known amount of internal standard 3,4,5-trimethoxybenzaldehyde. These results
      were compared with the conventional HPLC method. The advantages of the method are
      that no reference compounds are required for calibration curves, the
      quantification could be directly realized on a crude extract, an overall profile
      of the preparation could be directly obtained, and a very significant time-gain
      could be achieved, in comparison to conventional HPLC methods, for instance.

PMID- 15744116
TI  - [Neonatal lupus syndrome].
AB  - Neonatal lupus syndrome is a passively acquired autoimmune syndrome in which
      pathogenic autoantibodies (anti-SSA/Ro, anti-SSB/La, and both, or rarely anti
      U(1)RNP antibodies) are transmitted from a mother to her fetus through the
      placenta. The major clinical manifestations in the infants are cardiac
      (congenital heart block), dermatologic (skin lesion), hepatic (elevated hepatic
      enzymes), and hematologic (cytopenia). Congenital complete heart block (CCHB) is
      irreversible, while noncardiac manifestations are transient, resolving by one
      year-old of age without specific treatments. Two prospective studies show that
      the prevalence of CCHB in children from a woman previously known to have anti
      SSA/Ro antibodies is approximately 2%. However, when the previous pregnancy is
      complicated by CCHB and skin lesion, the recurrence rates of these symptoms go
      much higher to 10.5% and 26%, respectively, in the subsequent pregnancy.

PMID- 15744117
TI  - [Molecular mechanisms of salivary gland destruction in patients with Sjogren's
      syndrome. ].
AB  - IFNgamma plays an important role to induce several functional molecules on
      salivary epithelial cells, including class II MHC, Fas and CD40 in salivary
      glands from patients with Sjogren's syndrome (SS). IFNgamma also contributes to
      the development of lymphocytic infiltrates by inducing T cell attracting
      chemokines in SS salivary epithelial cells, such as IP-10 (CXCL10), Mig (CXCL9),
      and I-TAC (CXCL11). IFNgamma dysregulation in SS salivary gland may attribute to
      the decreased production of TGFbeta from salivary epithelial cells in some
      patients. Expression of Fas and CD40 was significantly higher in SS salivary
      epithelial cells than in normal cells after IFNgamma stimulation. Although
      neither anti-Fas (CH11) nor anti-CD40 mAb alone could induce typical apoptosis,
      the two together and preincubation with IFNgamma efficiently induced apoptosis in
      SS salivary epithelial cells. This apoptosis was almost completely blocked by
      neutralizing anti-Fas mAb (ZB4). c-FLIP, an important inhibitory molecule in the
      Fas death pathway, was strongly expressed in SS salivary epithelial cells, but
      its expression was downregulated, at the protein level, by anti-CD40 mAb. CD40
      signals promote Fas-dependent death of SS salivary epithelial cells by
      downregulating c-FLIP expression. The presence of c-FLIP in these cells may
      explain their resistance to undergo apoptosis in response to either anti-Fas or
      anti-CD40 mAb, despite their surface expression of both proteins. These findings
      suggest that SS salivary epithelial cell death requires the cooperation of Fas
      and CD40.

PMID- 15744118
TI  - [Regulation of immune response by T cell co-signaling. ].
AB  - The activation of naive T cells requires two signals from the antigen presenting
      cells (APC). Firstly, an antigen specific signal which is triggered by the
      binding of the T cell receptor (TCR) to the peptide-MHC complex, and secondly,
      antigen nonspecific signals initiated through a set of co-signalling receptors.
      Co-signalling molecules are cell-surface glycoproteins that play essential roles
      for the communication of a T cell with virtually all other host cells by
      modulating and fine-tuning TCR signals. On the basis of their functional outcome,
      co-signalling molecules can be divided into co-stimulators and co-inhibitors,
      which promote or suppress T-cell activation, respectively. By expression at the
      appropriate time and location, co-signalling molecules positively and negatively
      control the priming, growth, differentiation and functional maturation of a T
      cell response. In this article, I overview property of co-signaling molecules in
      the CD28- and TNFR family and discuss their potential functional relationships
      with each other. In addition, role of these co-signalling molecules in various
      diseases, such as autoimmune diseases, graft rejection, allergy, inflammatory
      bowel disease, and cancer, and the therapeutic potential of targeting these
      molecules to enhance or curtail an ongoing immune response in these diseases are
      discussed.

PMID- 15744119
TI  - [Anti-phosphatidylserine-prothrombin antibody in patients with recurrent abortion
      and preeclampsia].
AB  - AIM: The aim of the study was to describe the frequency of anti
      phosphatidylserine-prothrombin antibody(aPS/PTAb) in patients with recurrent
      abortion and preeclampsia, and to study the relationship between the presence of
      aPS/PTAb and clinical finding. Eighty six cases of recurrent abortion and 82
      cases of preeclampsia were studied. A aPS/PTAb was measured by an enzyme linked
      immunosorbent assay (ELISA). RESULTS: In patients with recurrent abortion, 3 out
      of 86 cases(3.4%) were positive in IgG antibody measurements and 5 out of
      86(5.8%) were positive in IgM antibody measurements. In patients with
      preeclampsia, 2 out of 82 cases(2.5%) were positive in IgG antibody measurements
      and 13 out of 82(16%) were positive in IgM antibody measurements. The positive
      rates of aPS/PTAb in severe hypertension-positive cases is greater than in
      hypertension-negative cases(p=0.045). The positive rates of aPS/PTAb is higher
      tendency with in severe type than in mild type(p=0.117). The positive rates of
      aPS/PTAb is higher tendency with proteinuria and/or hypertension than without
      proteinuria(p=0.098) or hypertension(p=0.096). CONCLUSION: We found that aPS/PTAb
      appears in some cases of patients with recurrent abortion and preeclampsia. Our
      data suggest that aPS/PTAb might be a risk factor in patients with recurrent
      abortion, and may relate to clinical finding in preeclampsia.

PMID- 15744120
TI  - [Quality of life in patients with systemic lupus erythematosus--preliminary
      survey using a short questionnaire. ].
AB  - Because the prognosis of systemic lupus erythematosus (SLE) has been much
      improved by recent progress in the treatment of this disease, improvement of
      quality of life (QOL) will be required more and more. However, QOL in SLE has not
      been well studied in comparison to that in rheumatoid arthritis. Fifty-four
      patients with systemic lupus erythematosus were asked about healthy feeling,
      acceptance of disease and the extent of satisfaction with their life. The
      percentage of patients who gave affirmative answers to healthy feeling,
      acceptance, and satisfaction was 64, 87, and 50, respectively. These three
      parameters were correlated with the following factors; 1. physical activity,
      especially that for daily living, 2. understanding in the family and workplace,
      and 3. depression and anxiety, whereas acceptance was not correlated with disease
      activity. Due to having a chronic disease, there are depression and anxiety
      derived from loss of existence in the family or workplace in their minds. In
      order to resolve these issues, education and explanation about the disease is
      needed for the family and society as well as for the patients. Although
      compliance of the patients in answering the questionnaire was easily obtained,
      the reliability and reproducibility, and the relationship between the items and
      the low-ranking factors should be investigated using a larger number of patients.

PMID- 15744121
TI  - [An autopsy case of intestinal Behcet's disease with sacroiliitis accompanied by
      myelodysplastic syndrome with trisomy 8. ].
AB  - Here we described an autopsy case of intestinal Behcet's disease with
      sacroiliitis associated with myelodysplastic syndrome (RAEB-t, 8+). Over twenty
      cases of Behcet's disease associated with myelodysplastic syndrome have been
      reported in preliterature so far. The majority of them are incomplete type of
      Behcet's disease having intestinal ulceration. Of those, trisomy 8 is the most
      common chromosomal abnormality. We reviewed similar cases reported and
      investigated the association of intestinal Behcet's disease with trisomy 8. The
      association of sacroiliitis with Behcet's disease is also studied.

PMID- 15744122
TI  - [A case of scleroderma-polymyositis overlap syndrome in which octreotide
      exacerbated abdominal symptoms].

PMID- 15744123
TI  - The air we breathe.

PMID- 15744124
TI  - Oh Lord! I've got those clinical research blues.

PMID- 15744125
TI  - Two third-year medical student-level laboratory shock exercises without large
      animals.
AB  - BACKGROUND: Historically, medical schools have taught principles of hemodynamic
      shock using large animal models. Such exercises are infrequent today due to the
      increasing aversion of students and the wider community to the use of large
      animals in teaching. Herein, we describe two alternative exercises that
      communicated basic science and clinical principles of shock effectively. METHODS:
      We developed two complementary, distinct single-afternoon laboratory exercises
      for third-year medical students. The first exercise (lab) demonstrated three
      principles: (1) in vitro cytokine-induced apoptosis (illustrating mechanisms and
      consequences of sepsis), (2) the hemodynamic manifestations of hypovolemia and
      septic shock in rats, and (3) the effects of fluid resuscitation or vasopressor
      administration in these same rat models. In the second exercise, students managed
      the diagnosis, initial resuscitation, surgical treatment, and ICU care of a
      "patient" with abdominal sepsis, using a manikin-based patient simulator and
      actual patient test data. Current basic science and clinical literature were
      incorporated. RESULTS: Efficacy was evaluated by polling students in one of four
      rotations (n = 25). Educational value of the lab exercise was rated 3.70 (1,
      worst rating; 5, best rating), whereas its applicability to clinical care was
      rated 4.35. Educational value and clinical applicability of the patient simulator
      were rated 4.52 and 4.76, respectively. CONCLUSIONS: These exercises combining
      laboratory demonstrations of the pathophysiologic mechanisms and manifestations
      of shock with simulation were judged effective and clinically relevant while
      fulfilling the National Institutes of Health (NIH) mandate to reduce use of
      experimental animals.

PMID- 15744126
TI  - Predictors of outcome for children with perforated appendicitis initially treated
      with non-operative management.
AB  - BACKGROUND: Initial non-operative therapy for children with perforated
      appendicitis has become increasingly popular with the advent of powerful broad
      spectrum antibiotics. However, there is no consensus regarding which patients may
      be managed effectively with this strategy. We reviewed all children with
      perforated appendicitis who were treated initially with non-operative therapy to
      determine those characteristics that may predict a successful outcome. METHODS:
      We reviewed the medical records of children admitted to our hospital between
      January 1, 2000 and May 1, 2003 with the diagnosis of perforated appendicitis.
      Only those who were treated initially with a single broad-spectrum antibiotic
      (piperacillin-tazobactam), with the intention of performing an interval
      appendectomy, were included in this study. Patients were divided into two groups
      based on whether they were managed successfully with non-operative therapy:
      Responders and non-responders. Non-responders were defined as patients who either
      did not improve with antibiotic therapy or who required appendectomy prior to
      their electively scheduled time (six weeks). Demographic data, duration and type
      of presenting symptoms, initial white blood cell count (WBC), percent bands,
      percent neutrophils (PMNs), computed tomography (CT) interpretation, and
      interventions/operations were abstracted. Categorical data were compared using
      Chi-square analysis or the Fisher exact test; continuous variables were compared
      using the Student t-test and the Mann-Whitney U-test. RESULTS: Overall, 26%
      (19/73) of patients treated initially non-operatively required appendectomy prior
      to the electively scheduled date. There was no difference between responders (n =
      54) and non-responders (n = 19) with respect to age, gender, initial WBC, percent
      bands, percent PMNs, or duration and type of presenting symptoms. However,
      responders were more likely to have a phlegmon on CT scan compared to non
      responders (11/54 vs. 0/19, p = 0.03). Non-responders were twice as likely to
      undergo drainage of an abscess by interventional radiology (10/19 vs. 13/54, p =
      0.02) compared to responders. Among all patients who required percutaneous
      drainage, the failure rate of non-operative management was 43% (10/23).
      CONCLUSIONS: Children with perforated appendicitis can be managed effectively
      with nonoperative therapy, even in the presence of intra-abdominal abscesses.
      However, the need for abscess drainage increases the failure rate, perhaps due to
      inadequate source control. Those patients with a phlegmon on CT scan as opposed
      to an abscess, are most likely to respond to non-operative management. Initial
      non-operative therapy of perforated appendicitis in children is appropriate under
      certain clinical circumstances, especially when the body itself or interventional
      radiology can achieve adequate source control.

PMID- 15744127
TI  - Influence of enteral and parenteral nutrition on splanchnic hemodynamics in
      septic patients.
AB  - BACKGROUND: Enteral nutrition is believed to augment splanchnic perfusion,
      thereby preserving splanchnic integrity, whereas parenteral nutrition does not
      offer this benefit. In an effort to study this, we compared splanchnic oxygen
      exchange and blood flow in critically ill, septic patients to normal controls
      during enteral or total parenteral nutrition. METHODS: Splanchnic oxygen exchange
      and hepatic blood flow characteristics in 14 critically ill, septic patients were
      compared to 19 normal controls while fasting and during nutrient administration.
      Nutrients were delivered as intraduodenal feedings or parenteral nutrition.
      Splanchnic hemodynamics were measured at baseline, 90 min, and 210 min during
      nutrient administration. Hepatic blood flow index (HBFI) by indocyanine green dye
      (ICG) clearance, splanchnic oxygen consumption index (SplVO(2)I), and hepatic
      venous oxygen saturation (ShvO(2)) were measured using hepatic venous
      catheterization. Plasma volume (PV) was measured from the volume of ICG
      distribution. Results were analyzed using population means (+/-SD) and one-way
      analysis of variance. RESULTS: There was no statistical change in HBFI,
      SplVO(2)I, PV or ShvO(2) over the study time interval within any group (p <
      0.05), irrespective of whether enteral or parenteral nutrition was the nutrient
      source. Septic patients, whether fasting or receiving nutrition, demonstrated
      higher HBFI and SplVO(2)I levels, whereas ShvO(2) levels were uniformly lower
      throughout the study compared to normal controls. CONCLUSIONS: Critically ill
      patients exhibited a hyperdynamic splanchnic state as indicated by the marked
      increase in HBFI and SplVO(2)I. However, neither nutrient regimen at clinically
      relevant rates altered splanchnic hemodynamics over the course of study. Thus,
      enteral nutrients do not appear to offer hemodynamic protection to the splanchnic
      system in critically ill patients.

PMID- 15744128
TI  - Longitudinal outcomes of intra-abdominal infection complicated by critical
      illness.
AB  - BACKGROUND: Critically ill surgical patients remain at high risk of adverse
      outcomes as a result of intra-abdominal infections, including prolonged length of
      stay, organ dysfunction, and death despite advances in critical care and
      innovations in management of the peritoneal cavity. We evaluated the causes and
      consequences of intra-abdominal infections among critically ill surgical patients
      in a single tertiary-care intensive care unit (ICU) over a decade. METHODS:
      Prospective study of 465 critically ill surgical patients with hollow viscus
      perforation and peritonitis or abscess from 1991-2002. Data collected were age,
      gender, admission APACHE III score, multiple organ dysfunction score, ICU and
      hospital length of stay, abscess (yes/no), site and type of perforation (colon
      vs. other), de novo vs. nosocomial origin, and mortality. Statistical analysis
      was by univariate ANOVA for coordinate data, Fisher exact test for continuous
      data, and logistic regression analysis. RESULTS: The incidence of intra-abdominal
      infection was 5.75%, 73.7% of the patients developed organ dysfunction, and
      mortality was 22.6%. Females comprised 46.8% of the patients. De novo infection
      represented 71.8% of cases, whereas nosocomial infection comprised 28.2% of
      cases. Perforations were of the colon (including the appendix) 49.9% of the time.
      An abscess formed in 22.3% of patients; the remainder had peritonitis but no
      abscess. Patients in the cohort with peritonitis were older (p = 0.0157), sicker
      on admission (p = 0.0411) and developed more organ dysfunction (p = 0.0072), but
      had the same rate of mortality. Despite steadily increasing acuity since 1991
      (r(2) = .71, p < 0.0001), the magnitude of organ dysfunction (r(2) = 0.11) and
      the mortality rate remained constant (r(2) = .01). By logistic regression,
      abscess correlated with less severe organ dysfunction (score > or = 5 [odds ratio
      0.54, 95% CI 0.33-0.90] and > or =9 points [odds ratio 0.38, 95% CI 0.20-0.74]),
      and increasing magnitude of organ dysfunction was associated with mortality (each
      point [odds ratio 1.46, 95% CI 1.32-1.61]). CONCLUSIONS: Although outcomes are
      improving, generalized peritonitis still causes high organ dysfunction-related
      mortality among critically ill surgical patients. Further improvements in
      resuscitation, surgical technique, and pharmacotherapy of severe intra-abdominal
      infections are needed.

PMID- 15744130
TI  - Adrenergic modulation of erythropoiesis following severe injury is mediated
      through bone marrow stroma.
AB  - BACKGROUND: Severe trauma leads to hematopoietic failure and bone marrow (BM)
      dysfunction that manifests clinically as a persistent anemia and leukopenia. The
      impact of severe trauma and its associated hyperadrenergic state on
      erythropoiesis has not been described. The aim of this study was to demonstrate
      the effects of adrenergic agonists and antagonists on erythropoiesis, both in
      normal bone marrow mononuclear cells (BMNC) and stroma-depleted BM. METHODS:
      Urine epinephrine (EPI) and norepinephrine (NE) excretion from severely injured
      patients was assessed via enzyme-linked immunoadsorbent assay (ELISA).
      Erythropoiesis was assessed by the growth of erythroid progenitors-erythroid
      burst forming units and colony forming units (BFU-E and CFU-E)-in normal human BM
      in the presence of adrenergic agonists and antagonists at varying concentrations.
      Parallel cultures, depleted of BM stroma by passage through nylon wool columns,
      were compared. RESULTS: Urine NE excretion was elevated in all samples from days
      1 to 10 following injury (average 139 +/- 59 mcg/day vs. control 35 +/- 9
      mcg/day). In vitro doses of NE, EPI, and isoproterenol (ISO) exerted a
      stimulatory effect on BFU-E colony growth in BMNCs (expressed as percentage of
      control: 324 +/- 30, 272 +/- 16, 212 +/- 95, vs. 100%), but had no effect on
      stroma-depleted BM. CONCLUSIONS: There is a substantial and persistent
      hyperadrenergic state seen after severe injury that may last for up to a week.
      Adrenergic agonists have a clear stimulatory effect on the growth of primitive
      erythroid precursors in normal BM. The adrenergic stimulus appears to be mediated
      via BM stroma.

PMID- 15744129
TI  - Sepsis-induced changes in macrophage co-stimulatory molecule expression: CD86 as
      a regulator of anti-inflammatory IL-10 response.
AB  - BACKGROUND: Sepsis remains a substantial risk after surgery or other trauma.
      Macrophage dysfunction, as a component of immune suppression seen during trauma
      and sepsis, appears to be one of the contributing factors to morbidity and
      mortality. However, whereas it is known that the ability of macrophages to
      present antigen and express major histocompatibility complex MHC class II
      molecules is decreased during sepsis, it is not known to what extent this is
      associated with the loss of co-stimulatory receptor expression. Our objectives in
      this study were, therefore, to determine if the expression of co-stimulatory
      molecules, such as CD40, CD80, or CD86, on peritoneal/splenic/liver macrophages
      were altered by sepsis (cecal ligation [CL] and puncture [CLP] or necrotic tissue
      injury (CL) alone; and to establish the contribution of such changes to the
      response to septic challenge using mice that are deficient in these receptors.
      METHODS: To address our first objective, male C3H/HeN mice were subjected to CLP,
      CL, or sham (n = four to six mice/group), and the adherent macrophages were
      isolated from the peritoneum, spleen, or liver at 24 h post-insult. The
      macrophages were then analyzed by flow cytometry for their ex vivo expression of
      CD40, CD80, CD86, and/or MHC II. RESULTS: The expression of CD86 and MHC II, but
      not CD40 or CD80, were significantly decreased on peritoneal macrophages after
      the onset of sepsis or CL alone. In addition, CD40 expression was significantly
      increased in Kupffer cells after sepsis. Alternatively, splenic macrophages from
      septic or CL mice did not show changes in the expression of CD80, CD86, or CD40.
      To the degree that the loss of CD86 expression might contribute to the changes
      reported in macrophage function in septic mice, we subsequently examined the
      effects of CLP on CD86 -/- mice. Interestingly, we found that, unlike the
      background controls, neither the serum IL-10 concentrations nor the IL-10 release
      capacity of peritoneal macrophages from septic CD86 -/- mice were increased.
      CONCLUSION: Together, these data suggest a potential role for the co-stimulatory
      receptor CD86/B7-2 beyond that of simply promoting competent antigen presentation
      to T-cells, but also as a regulator of the anti-inflammatory IL-10 response. Such
      a role may implicate the latter response in the development of sepsis-induced
      immune dysfunction.

PMID- 15744131
TI  - Allogenic blood transfusion in the first 24 hours after trauma is associated with
      increased systemic inflammatory response syndrome (SIRS) and death.
AB  - BACKGROUND: Previous studies have documented that blood transfusion incites a
      substantial inflammatory response with the systemic release of cytokines.
      Furthermore, blood transfusion is a significant independent predictor of multiple
      organ failure in trauma. The objective of this study was to assess the risk of
      systemic inflammatory response syndrome (SIRS) and intensive care unit (ICU)
      admission, length of stay (LOS), and mortality in trauma patients who require
      blood transfusion. METHODS: Prospective data were collected on 9,539 trauma
      patients admitted to the R. Adams Cowley Shock Trauma Center over a 30-month
      period from January, 1997 to July, 1999. Complete SIRS data were available on
      7,602 patients. Patients were stratified by age, gender, race, Glasgow coma scale
      (GCS), and injury severity score (ISS). A systemic inflammatory response to a
      wide variety of severe clinical insults (SIRS) was defined as a SIRS score of >
      or =2, as calculated on admission. Blood transfusion was assessed as an
      independent predictor of SIRS, ICU admission and length of stay, and mortality.
      RESULTS: The mean age of the study cohort was 37 +/- 17 years; the mean ISS was 9
      +/- 9 points. Seventy-one percent of the patients were male, and 85% sustained
      blunt trauma. Blood transfusion within the first 24 h was administered to 954
      patients, comprising 10% of the study cohort. Transfused patients were
      significantly older (43 +/- 20 vs. 36 +/- 16 years, p < 0.00001), had higher ISS
      (22 +/- 12 vs. 8 +/- 7 points, p < 0.00001), and lower GCS (12 +/- 4 vs. 14 +/- 2
      points, p < 0.00001) than non-transfused patients. Blood transfusion and
      increased total volume of blood transfusion was associated with SIRS. Blood
      transfusion was also a significant independent predictor of SIRS, ICU admission,
      and mortality in trauma patients by multinomial logistic regression analysis.
      Trauma patients who received blood transfusion had a two- to nearly sixfold
      increase in SIRS (p < 0.0001) and more than a fourfold increase in ICU admission
      (OR 4.62, 95% CI 3.84-5.55, p < 0.0001) and mortality (OR 4.23, 95% CI 3.07-5.84,
      p < 0.0001) compared to those that were not transfused. Linear regression
      analysis revealed that transfusion was an independent predictor of ICU LOS (Coef.
      5.20, SE 0.43, p < 0.0001). Transfused patients had significantly longer ICU LOS
      (16.8 +/- 14.9 vs. 9.9 +/- 10.6 days, p < 0.00001) and hospital LOS (14.5 +/-
      15.5 vs. 2.5 +/- 5.3 days, p < 0.00001) compared to non-transfused patients.
      CONCLUSIONS: Blood transfusion within the first 24 h was an independent predictor
      of mortality, SIRS, ICU admission, and ICU LOS in trauma patients. The use of
      blood substitutes and alternative agents to increase serum hemoglobin
      concentration in the post-injury period warrants further investigation.

PMID- 15744137
TI  - Clinical implications of peripapillary atrophy in glaucoma.
AB  - PURPOSE OF REVIEW: To elucidate peripapillary atrophy in glaucomatous optic
      neuropathy; its ranking in the morphologic diagnosis of the glaucoma, and its
      value for the differentiation of various types of chronic open-angle glaucoma,
      for the separation of glaucomatous eyes from nonglaucomatous eyes, and for the
      detection of progression of glaucoma. RECENT FINDINGS: Recent studies showed an
      association of peripapillary atrophy with glaucoma and the eventual development
      of glaucomatous disc hemorrhages independent of a small neuroretinal rim area,
      and an association between increasing peripapillary atrophy and progressive
      glaucoma. A ranking of optic disc parameters to detect glaucomatous damage
      revealed that the alpha and beta zones of peripapillary atrophy, compared with
      neuroretinal rim parameters, are less useful. Pseudoexfoliation syndrome without
      glaucoma is not a risk factor for peripapillary atrophy. In arteritic anterior
      ischemic optic neuropathy, peripapillary atrophy does not enlarge. Peripapillary
      atrophy does not differ markedly between Europeans and South Indians. In contrast
      to the position of the central retinal vessel trunk, the presence and position of
      cilioretinal arteries do not markedly influence the progression of peripapillary
      atrophy in glaucoma. SUMMARY: Peripapillary chorioretinal atrophy is one among
      several morphologic variables to detect glaucomatous abnormalities. Ranking optic
      disc variables for the detection of glaucomatous optic nerve damage,
      peripapillary atrophy is a variable of second order. It is useful for the
      differentiation of various types of chronic open-angle glaucomas. In contrast to
      glaucomatous eyes, eyes with nonglaucomatous optic nerve atrophy, including eyes
      after arteritic anterior ischemic optic neuropathy, do not show an enlarged
      peripapillary atrophy.

PMID- 15744136
TI  - Blood flow in glaucoma.
AB  - PURPOSE OF REVIEW: Glaucoma, one of the leading causes of blindness in the world,
      is characterized by progressive visual field loss and distinctive excavation of
      the optic nerve head. Although elevated intraocular pressure is the major risk
      factor, there is increasing evidence that the pathogenesis of glaucoma is also
      linked to altered ocular blood flow. This review summarizes the recent
      publications relevant to blood flow in glaucoma. RECENT FINDINGS: Several studies
      indicate that a perfusion instability, rather than a steady reduction of ocular
      blood flow, might contribute to glaucomatous optic neuropathy. The main cause of
      the instability is a disturbed autoregulation in the context of a general
      vascular dysregulation. The underlying mechanism of such a vascular dysregulation
      is not known. A dysfunction of both the autonomic nervous system and vascular
      endothelial cells is discussed. SUMMARY: The mechanical and vascular theories are
      not mutually exclusive; on the contrary, a vascular dysregulation increases the
      susceptibility to intraocular pressure. Therapeutically, therefore, both an
      intraocular pressure reduction and an improvement of the ocular blood flow might
      be considered.

PMID- 15744138
TI  - Glaucoma lasers: a review of the newer techniques.
AB  - PURPOSE OF REVIEW: This paper serves to review the safety and efficacy of new
      laser techniques for the treatment of glaucoma with emphasis on those studies
      published within the past year. RECENT FINDINGS: Recently published studies have
      reinforced the strong safety profile, and efficacy of selective laser
      trabeculoplasty (SLT). Endoscopic photocoagulation, while more technically
      challenging and more invasive, offers several advantages over transcleral
      cyclophotocoagulation including direct observation of treatment and therefore,
      fewer complications. Laser goniopuncture is a fledgling technology with, thus
      far, a good safety profile, and benefits that include conjunctival sparing and
      good treatment response. Many unanswered questions remain including long-term
      success rates and ideal treatment parameters. SUMMARY: The benefits of laser in
      the treatment of glaucoma have been well established, and while some techniques
      will add to the ophthalmologists' armamentarium, others will fall into disuse as
      the efficacy and safety profiles of these procedures become recognized. Novel
      laser modalities, as well as the more traditional ones, require continued
      evaluation to further refine treatment parameters and to determine their long
      term benefits.

PMID- 15744139
TI  - Glaucoma medication and aqueous humor dynamics.
AB  - PURPOSE OF REVIEW: This review evaluates current concepts regarding the effects
      of glaucoma medication on aqueous humor dynamics and the impact of this on
      intraocular pressure control and drug selection in clinical practice. RECENT
      FINDINGS: Calculations based on the Friedenwald and Goldmann equations have
      predicted that glaucoma medications that increase pressure-sensitive aqueous
      outflow will dampen intraocular pressure spikes and therefore may be advantageous
      over drugs that do not increase outflow facility. SUMMARY: Further experimental
      research is required to verify the influence of increased outflow facility on
      intraocular pressure fluctuation and the effect of this on glaucoma progression.

PMID- 15744140
TI  - Ethnic differences in glaucoma: prevalence, management, and outcome.
AB  - PURPOSE OF REVIEW: Glaucoma has a disproportionate prevalence among specific
      ethnic groups. Therefore, the issue of 'race' and glaucoma has been the focus of
      much discussion. The purpose of this article is to provide a review of the
      literature regarding the prevalence, management, and outcome of glaucoma among
      different ethnic populations. RECENT FINDINGS: This review highlights not only
      recent reports but also notes key studies from the past regarding glaucoma and
      ethnicity. Given the variation in presentation and the response to therapy, it is
      important to individualize one's therapeutic approach in any given patient.
      SUMMARY: Our knowledge regarding glaucoma and ethnicity helps us to customize a
      patient's therapeutic regimen more effectively. Therefore, understanding an
      individual's heredity and culture is essential to properly identify, treat, and
      manage individuals at risk and existing patients with glaucoma.

PMID- 15744141
TI  - Recent advances in trabeculectomy technique.
AB  - PURPOSE OF REVIEW: Trabeculectomy is an effective operation for lowering
      intraocular pressure. However, success is limited by complications such as
      infection, hypotony, and scarring. RECENT FINDINGS: These complications, which
      are increased by antifibrotic use, can be reduced with attention to surgical
      technique. We highlight the benefit of sub-Tenon anaesthesia, careful choice of
      the surgical site, fashioning of the scleral flap to produce diffuse aqueous
      flow, and better intraocular pressure control, maintenance of intraocular
      pressure, a formed anterior chamber, with outflow control during surgery using an
      infusion, optimal method of antimetabolites application, new adjustable sutures,
      and corneal-conjunctival closure techniques. SUMMARY: These techniques reduce
      hypotony, producing a diffuse noncystic bleb with long-term pressure control.

PMID- 15744142
TI  - Compliance and persistency in glaucoma follow-up treatment.
AB  - PURPOSE OF REVIEW: To summarize research published between 1980 and October 2004
      regarding compliance (the extent to which patients' behaviors correspond with
      providers' recommendations) and persistency (total time on therapy) in patients
      diagnosed with open-angle glaucoma or ocular hypertension; to suggest approaches
      ophthalmologists might consider to improve compliance and persistency; and to
      identify areas warranting future research. RECENT FINDINGS: Medication
      compliance, the focus of most compliance-related research, has been measured
      using a variety of methods including patient self-reports, the medication
      possession ratio, and electronic monitoring. Noncompliance rates of at least 25%
      commonly have been reported. The primary obstacles to medication compliance
      appear to be situational/environmental (e.g., being away from home or a change in
      routine) or related to the medication regimen (e.g., side effects or complexity).
      Persistency with ocular hypotensive therapies has been found to be poor.
      Retrospective cohort studies using survival analyses have reported that fewer
      than 25% of patients are persistent over 12 months. SUMMARY: Accurately assessing
      patient compliance and persistency is important to optimizing patient care.
      Physicians may mistake either medication noncompliance or lack of persistency
      with poor efficacy. Such errors would likely increase health care costs if they
      result in unnecessary changes to a patient's therapeutic regimen or in surgery.

PMID- 15744143
TI  - Bibliography. Bibliography current world literature. Glaucoma.

PMID- 15744146
TI  - Safety of magnetic resonance imaging of stapes prostheses.
AB  - OBJECTIVE: Assess the safety of performing magnetic resonance imaging (MRI) on
      patients with stapes prostheses. STUDY DESIGN: Survey and animal model. METHODS:
      A survey regarding implant usage, MRI procedures, and adverse outcomes after MRI
      in patients previously undergoing stapes procedures. Guinea pigs implanted with
      ferromagnetic 17 to 4 stainless steel, 316L nonferromagnetic stainless steel,
      titanium, and fluoroplastic stapes prostheses underwent a MRI in a 4.7 Tesla MR
      system. RESULTS: : Three adverse outcomes were reported on the clinical survey.
      One adverse event occurred during an MRI performed on a recalled ferromagnetic
      prosthesis. The other two adverse events were probably not secondary to MRI
      exposure. No damage or inflammation was observed in the region of the oval window
      or vestibule of implanted guinea pigs exposed to a 4.7 Tesla MR system.
      CONCLUSIONS: The combination of prior studies, the clinical survey, and the
      absence of histopathologic evidence of damage in the guinea pigs is compelling
      evidence that MRI for patients with stapes prostheses is safe. Implanting
      physicians should feel comfortable clearing a patient for a MRI in a 1.5 Tesla or
      3.0 Tesla MRI. It is imperative for the physician to qualify the field strength
      when clearing a patient to undergo a MRI.

PMID- 15744147
TI  - Combination nonviral interleukin-2 gene immunotherapy for head and neck cancer:
      from bench top to bedside.
AB  - OBJECTIVE/HYPOTHESIS: Intralesional delivery of cytokine genes has emerged as a
      promising therapeutic strategy for the treatment of cancer. In addition to the
      therapeutic effect of the delivered cytokine gene, the components of the gene
      delivery system also have been shown to induce beneficial immune responses. On
      the basis of these principles, we hypothesized that a molecular therapy could be
      developed that would provide synergistic antitumor activity by way of
      intralesional expression of interleukin (IL)-2 from a recombinant plasmid
      combined with induction of endogenous interferon (IFN)-gamma and IL-12 cytokines
      by immunostimulatory DNA. Our objective in these studies was to create and
      optimize a novel formulation of cationic lipid and DNA that generates local
      production of IL-2 protein within a targeted tumor environment with concomitant
      induction of the antitumor cytokines IFN-gamma and IL-12. STUDY DESIGN:
      Prospective laboratory drug development plan that would produce human clinical
      trials. MATERIALS AND METHODS: Engineered bacterial plasmids containing a
      cytomegalovirus promoter (CMV)-IL-2 expression cassette were specifically
      formulated with cationic lipids and optimized for antitumor effect in a floor of
      mouth murine tumor model. The treated tumors were assayed for local expression of
      IL-2 and concurrent expression of secondary cytokines IFN-gamma and IL-12.
      Established tumors in C3H/HeJ mice were treated with various IL-2 gene
      formulations, and clinical and immunologic responses were evaluated. Immunologic
      studies were performed and included cytolytic T-cell assays and cytokine
      expression profiles. For human clinical trials, a phase I 10 patient formulated
      IL-2 gene therapy study was completed. Subsequently, two large scale, phase II
      multi-institutional and multi-international studies were initiated comparing non
      viral IL-2 gene therapy to palliative methotrexate chemotherapy or in combination
      with cisplatin. RESULTS: In the preclinical stage, maximum tumor inhibition in
      animal models was obtained using IL-2 plasmid formulated with 1,2
      dioleyloxypropyl-3-trimethyl ammonium chloride (DOTMA):cholesterol (1:1 mol:mol)
      at a plasmid:lipid charge ratio of 1:0.5 (-/+). Cationic lipid formulated IL-2
      plasmid significantly inhibited tumor growth compared with formulated control
      plasmid (P < .01) or vehicle (lactose; P < .01). Consistent with previously
      reported studies of the immunostimulatory activity of DNA of bacterial origin,
      treatment of tumors with control plasmid in cationic lipid formulation induced
      production of endogenous IFN-gamma and IL-12 but not IL-2. Treatment of tumors
      with formulated IL-2 plasmid produced IL-2 protein levels that were 5-fold over
      background and increased IFN-gamma by 32-fold (P < .001) and IL-12 by 5.5-fold (P
      < .001) compared with control plasmid formulations. The phase I human trial
      demonstrated dose escalation safety, which was its primary objective, and there
      was one anecdotal reduction in tumor size. The phase II studies have been
      initiated and focus on either comparing the novel nonviral IL-2 gene
      immunotherapy formulation alone to methotrexate or comparing IL-2 gene therapy in
      combination with cisplatin in recurrent or unresectable patients with head and
      neck squamous cell carcinoma. CONCLUSIONS: The preclinical data provided proof of
      principle for matching a delivered IL-2 transgene with an immunostimulatory
      nonviral formulation to enhance intralesional production of therapeutic cytokines
      for the maximization of antitumor response. Human clinical trials have
      demonstrated this novel therapy to be safe in the human clinical setting. Phase
      II trials have been initiated to assess efficacy and feasibility as a single or
      combination therapy for head and neck cancer.

PMID- 15744148
TI  - Effects of age and diet on rat skin histology.
AB  - OBJECTIVE/HYPOTHESIS: To document age-related histologic morphometric changes of
      rat skin and the effects of calorie restriction on such changes. STUDY DESIGN:
      Fischer 344 rats of three age groups (young, 4 mo; adult, 1 year; old, 24+
      months) were procured from ad libitum (AL) diet and calorie-restricted (CR)
      colonies of the National Institute of Aging and were used for histologic study.
      Each study group consisted of six animals. METHODS: Skin samples from the dorsum
      (DS) and footpad (FP) of these animals were excised and processed for histology
      with staining techniques for general morphology (hematoxylin-eosin-phloxine) and
      for differentiation of collagen bundles and elastic fibers (Verhoeff-van Gieson
      technique). Light microscopic morphometric and stereologic point counting
      procedures were applied manually to tissue sections to obtain quantitative data
      on the depth of the epidermis, dermis, and stratum corneum, epidermal nuclear
      number, and percentage fraction of collagen, elastic fibers, capillaries, and
      pilosebaceous units. Data were analyzed with two-way of analysis of variance
      (ANOVA) to determine significant effects of age, diet, and age-diet interaction
      on these parameters in AL rats and their age-matched cohorts. RESULTS:
      Significant effects of age, diet, or age-diet interaction were observed in
      respect of the thickness of epidermis, dermis, stratum corneum of FP, epidermal
      nuclear number, collagen percentage fraction, and area fraction of capillaries.
      DS epidermis showed increasing thickness in AL group, but this was reduced in CR
      rats. A similar trend in DS dermal depth was observed. Fewer capillaries were
      present in aging CR rats. The DS epidermal nuclear profiles and collagen area
      fraction also showed effects of diet and age-diet interaction. Aging changes,
      especially the effect of CR, was more evident in the measured parameters of
      dorsal skin. No alterations were observed in the distribution of pilosebaceous
      units and elastic fiber profiles of the skin. CONCLUSIONS: The Fischer 344 rat
      shows many age-related changes in the skin, some of which are different from data
      reported in literature. The pattern of aging changes in skin parameters was
      different in the two groups, suggesting an in influence of CR. CR appears to
      modify the aging rate of some skin components, and this may be caused by
      metabolic changes imposed by diet.

PMID- 15744149
TI  - Improving surgical wound healing with basic fibroblast growth factor after
      radiation.
AB  - OBJECTIVES/HYPOTHESIS: Delayed wound healing in surgical patients who have
      received previous irradiation continues to be a significant problem. We
      investigated whether radiation decreases basic fibroblast growth factor (bFGF)
      production in skin and whether supplemental bFGF can improve irradiated
      postsurgical soft tissue healing. STUDY DESIGN: Experimental study in the porcine
      skin flap model. METHODS: Pigs were subjected to orthovoltage radiation (1,300
      cGy). To test whether radiation alters bFGF production in skin, semiquantitation
      of bFGF message was compared in irradiated and nonirradiated skin by reverse
      transcription-polymerase chain reaction (RT-PCR). To determine whether
      supplemental bFGF can improve postsurgical soft tissue healing after radiation,
      bFGF was given intravenously or intracuticularly preoperatively. To investigate
      whether additional oxygen tissue levels would modify the effects of supplemental
      bFGF, one test group received hyperbaric oxygen. Six weeks later, 108 skin flaps
      (random and arterial) were created in 27 pigs and monitored over 2 weeks. Tissues
      were analyzed for flap viability, vascularity, endothelial cell apoptosis by
      caspase-3 activation, and histologic analysis. RESULTS: Radiation statistically
      increased endothelial cell apoptosis in porcine skin by 650%. Radiation also
      significantly reduced bFGF message by 75% in porcine skin by RT-PCR analysis.
      Supplemental intravenous bFGF in irradiated tissue significantly increased skin
      flap viability by 25% compared with controls (P < .001). Intravenous bFGF also
      significantly reduced gastrointestinal side effects from irradiation by 50%
      compared with controls. BFGF treatment induced a trend to decrease endothelial
      cell apoptosis in irradiated skin, but this was not statistically significant.
      Histologically, the intravenous bFGF-treated flaps had similar cellularity,
      fibroblasts, and extracellular acid mucopolysaccharides as controls. When bFGF
      was administered by intracuticular injection with and without hyperbaric oxygen,
      skin flap survival and flap vascularity were similar to controls. CONCLUSIONS:
      Decreased local levels of bFGF in skin may play an important role in the delayed
      healing of irradiated wounds. Radiation appears to decrease bFGF production by
      significantly reducing bFGF message in irradiated tissue. Supplemental
      intravenous bFGF reduced irradiated soft tissue injury and improved random skin
      flap viability in this porcine model. More studies are needed to investigate the
      effects of bFGF in the surgical healing of irradiated wounds.

PMID- 15744150
TI  - Stroboscopy as a research instrument: development of a perceptual evaluation
      tool.
AB  - Laryngeal stroboscopy is arguably the most important clinical tool for the
      evaluation and treatment of patients with voice disorders. Unfortunately, at
      present, laryngeal stroboscopy is strictly a clinical tool and has no definitive
      use in the area of voice research. The limitation with laryngeal stroboscopy is
      the subjective nature of the interpretation of the video examination. A video
      stroboscopy research tool was developed using 10 stroboscopic parameters selected
      from the literature and clinical practice. The stroboscopy research tool was
      validated with the results of 18 reviewers using the instrument to rate 21 unique
      "cases" and 6 repeated "cases." The results of this video perceptual analysis
      study identified which parameters were the most robust and reliable across a wide
      range of reviewers and validated power analysis curves for future similar
      research. Furthermore, findings from this study revealed that a greater than 80%
      intra-rater reliability is the preferred method for the selection of a valid and
      reliable reviewer. Future research using this instrument will most likely
      increase the reliability and utility of the instrument with the use of prestudy
      reviewer training and/or the use of video examples to serve as anchors or
      external references.

PMID- 15744151
TI  - Analysis of recurrence and survival after hypopharyngeal ablative surgery with
      radial forearm free flap reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: To address the controversial acceptable distal resection
      margin for the surgical management of patients with hypopharyngeal cancer. STUDY
      DESIGN: Retrospective review of the records of 28 consecutive patients who
      underwent pharyngoesophagectomy and reconstruction with radial forearm free flaps
      between 1996 to 2001. METHODS: The Kaplan-Meier method was used to estimate
      survival and recurrence-free time. RESULTS: The minimum follow-up time was 2
      years, and there were 14 (50%) patients who had recurrences. Analysis revealed
      that only one (3%) patient experienced a recurrence at the inferior resection
      margin, the junction of the free flap reconstruction, and the cervical esophagus.
      Estimated 4 year survival was 48.5%. CONCLUSIONS: Total laryngopharyngectomy and
      partial esophagectomy with radial forearm free flap reconstructions in
      appropriately selected patients with hypopharyngeal cancer does not compromise
      local recurrence rates at the distal esophageal margin.

PMID- 15744152
TI  - Fine-needle aspiration biopsy findings suspicious for papillary thyroid
      carcinoma: a review of cytopathological criteria.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to evaluate the usefulness of standard
      suspect cytological features on fine-needle aspiration biopsy (FNAB) in
      predicting papillary thyroid carcinoma. STUDY DESIGN: Retrospective chart review
      of consecutive fine-needle biopsies of the thyroid. METHODS: The study was a
      retrospective review of consecutive patients presenting with a diagnosis of
      suspected (group 1) or positive papillary thyroid carcinoma (group 2). The
      frequency of standard cytological features (i.e., papillary architecture,
      multinucleated giant cell, nuclear pseudo-inclusions, nuclear grooves,
      micronucleoli, powdery chromatin, and psammoma bodies) were recorded for each
      group. These were compared using chi test. Sensitivity and specificity for both
      individual and a combination of features were calculated for patients in group 1.
      RESULTS: One hundred eight patients were eligible for the study (group 1, n = 57;
      group 2, n = 51). Fifty-one patients (89%) in group 1 and all patients in group 2
      had a histopathological diagnosis of papillary thyroid carcinoma. Respectively,
      the most frequent features present on fine-needle aspiration biopsy in group 1
      versus group 2 were nuclear grooves (79% vs. 88%), micronucleoli (74% vs. 86%),
      pseudo-inclusions (58% vs. 88%), and powdery chromatin (47% vs. 59%); P values
      for these features were P > .05, P > .05, P < .05, and P > .05, respectively. In
      group 1, the sensitivities of nuclear grooves and micronucleoli were 80% and 71%,
      respectively. The presence of psammoma bodies was associated with a specificity
      of 100%. A combination of nuclear grooves, micronucleoli, pseudo-inclusions,
      powdery chromatin, and multinucleated giant cells was 100% specific in detecting
      papillary thyroid carcinoma. CONCLUSION: In choosing the most appropriate
      management of a finding suspect for papillary thyroid carcinoma on fine-needle
      aspiration biopsy, the surgeon must be aware of the diagnostic importance of
      certain cytopathological features. The presence of a combination of these factors
      may allow a more confident surgical approach.

PMID- 15744153
TI  - Nasal valve surgery improves disease-specific quality of life.
AB  - OBJECTIVES/HYPOTHESIS: Disease-specific quality-of-life (QOL) assessment of
      patients with nasal valve compromise and symptomatic nasal obstruction has not
      been studied previously. The objectives of the study were to determine whether
      surgical treatment of the nasal valve improves disease-specific QOL and to
      identify clinical or demographic variables predictive of patients' baseline QOL
      or change in QOL. STUDY DESIGN: Prospective, multi-institutional outcomes study
      of 20 patients with nasal obstruction and a surgically treatable diagnosis of
      nasal valve compromise. METHODS: Disease-specific QOL assessment was performed
      using the Nasal Obstruction Symptom Evaluation (NOSE) scale preoperatively (n =
      20) and at 3 (n = 14) and 6 months (n = 20) after surgery. Clinical and
      demographic data were collected, along with physician-reported assessments of
      degree of nasal obstruction. RESULTS: Mean NOSE scores significantly improved
      from baseline to 3 months after surgery (68.9 vs. 20.7 [P < .0001]), from
      baseline to 6 months after surgery (68.9 vs. 15.8 [P < .0001]), and from 3 to 6
      months after surgery (20.7 vs. 15.8 [P = .0077]). Physician assessment of degree
      of nasal obstruction using a visual analogue scale was significantly correlated
      with baseline NOSE scores (P = .013) and change in NOSE scores at 6 months (P =
      .0015). No other clinical or demographic factors were found to be predictive.
      CONCLUSION: In patients with symptomatic nasal obstruction and nasal valve
      compromise, surgical repair of the nasal valve improves disease-specific QOL.
      Physician rating of degree of nasal obstruction was found to be significantly
      correlated with patient-reported QOL.

PMID- 15744154
TI  - Protecting medical record information: start your research registries today.
AB  - OBJECTIVE: The Health Insurance Portability and Accountability Act (HIPAA) of
      1996 was enacted with the long-term goal of improving the efficiency and
      effectiveness of health care. It has created sweeping changes for clinical
      medicine and research. Generally, the standards for privacy of individual,
      identifiable health information (the privacy rule) require patient consent before
      their protected health information (PHI) can be employed in clinical research.
      This rule requires that all patients sign an IRB approved informed consent before
      their identifiable clinical information can be aggregated with the information
      from other patients. This rule has been applied to ensure the privacy of health
      care data accrued previously. Accordingly, investigators have been blocked from
      using the aggregate data from prior clinical records and registries until consent
      is obtained from living, former patients. At the University of Pittsburgh
      Department of Otolaryngology, a clinical tumor registry was established in 1982.
      These data have served as the basis for over 200 publications reflecting practice
      based learning. The present study quantifies the cost of HIPAA compliance to
      maintain access to our faculty's career-long clinical activities and to stress to
      all physicians the importance of research registries as a means of protecting
      their own career's work. RESULTS/CONCLUSIONS: Compliance with the privacy rule
      required that written, informed consents be mailed to 14,330 former patients.
      This resulted in direct costs of more than $30,888. The practical and financial
      impact of HIPAA on clinical research and our departmental solutions to these
      challenges are discussed.

PMID- 15744155
TI  - Cochlear implantation at under 12 months: report on 10 patients.
AB  - OBJECTIVES: There is growing evidence that early application of a cochlear
      implant in children affected by profound congenital hearing loss is of paramount
      importance for the development of an adequate auditory performance and language
      skills. For these reasons and as a result of advances in audiologic diagnosis and
      an enhanced awareness of the safety of cochlear implants, the age of implantation
      has substantially decreased over recent years. Children aged as little as 12
      months are now being implanted in some centers. On the basis of our experience
      with very young children, we believe that the date of implantation may be further
      reduced to only 4 to 6 months of age. STUDY DESIGN: Over the period from November
      1998 to April 2004, 103 children have been fitted with cochlear implants and 11
      with auditory brainstem implants in our department, including 65 children aged
      below 3 years. The present study focuses on 10 children aged less than 12 months
      fitted with cochlear implants from November 1998 to December 2003. METHODS: The
      children's ages ranged from 4 to 11 (mean 9.5) months. Five were males and five
      females. All received a Nucleus CI 24 M. Postoperative auditory performance, as
      evaluated at the latest follow-up, was based on the category of auditory
      performance (CAP). The results obtained in these 10 children were compared with
      those obtained with cochlear implants in children belonging to older age
      brackets. The criteria used to assess speech performance were onset of babbling
      onset and babbling spurt, and the results observed were compared with those of a
      control group of 10 normally hearing children. RESULTS: Surgery was uneventful,
      and no immediate or delayed complications were encountered. Auditory performance
      was seen to increase as function of early age of implantation and length of
      implant use. All 10 children had a CAP score of 3 within 6 months of cochlear
      implant activation. The onset of babbling occurred very early (i.e., within 1 to
      3 months of activation of the implant in all 10 patients), regardless of age at
      implantation, whereas the babbling spurt was recorded at times ranging from 3 to
      5 months after implant activation. The positive impact of early implantation on
      babbling was clearly shown by the fact that the earlier the activation of the
      cochlear implant, the closer the results were to the outcomes of normally hearing
      children. CONCLUSIONS: We encourage very early implantation to facilitate a
      series of developmental processes occurring in the critical period of initial
      language acquisition. The indices we used in the present study (i.e., CAP and
      babbling) suggest that early cochlear implantation tends to yield normalization
      of audio-phonologic parameters, which enables us to consider the performance of
      children implanted very early as being similar to that of their normally hearing
      peers.

PMID- 15744156
TI  - Conservative management of acoustic neuroma: a meta-analysis and proposed
      treatment algorithm.
AB  - OBJECTIVES/HYPOTHESES: Conservative management is a viable treatment alternative
      for acoustic neuroma. Using previous studies to provide evidence-based support,
      we have attempted to more clearly define the role of conservative management.
      STUDY DESIGN: Retrospective review of literature and patient charts. METHODS:
      Published studies on conservative management of acoustic neuroma were found using
      a key word search through PubMed in addition to the bibliographies of these
      selected studies. A spreadsheet was made to tabulate the selection criteria for
      conservative management, duration and frequency of follow-up, patient
      demographics, initial tumor size and rate of growth, change in hearing status,
      and the need for definitive treatment. RESULTS: A total of 21 studies comprising
      1,345 patients were included in our meta-analysis. The average length of follow
      up these studies was 3.2 years. The average initial tumor size was 11.8 mm (n =
      900); 43% of 1,244 acoustic neuromas showed growth, whereas 57% showed either no
      growth or tumor regression. The average growth rate was 1.9 mm/year in 793
      individuals. Hearing loss occurred in 51% of 347 individuals. In 15 studies,
      20.0% of 1,001 individuals eventually failed conservative management.
      CONCLUSIONS: Our meta-analysis supports the role of conservative management of
      acoustic neuromas in properly selected patients on the basis of a slow overall
      rate of growth and a substantial incidence of no growth. However, the lack of
      predictive factors, the relatively short duration of follow-up, and the
      variability of inclusion criteria underscore the need for continued collection of
      long-term data. An algorithm for acoustic neuroma management is proposed based on
      initial tumor size, patient age, and hearing status.

PMID- 15744157
TI  - Classification of the external auditory canal cholesteatoma.
AB  - OBJECTIVES/HYPOTHESIS: The external auditory canal cholesteatoma (EACC) is a rare
      disease in the field of otolaryngology. Only 1 in 1,000 new otologic patients
      present with this entity, which was first described by Toynbee. The aim of this
      article is to classify EACC by different histopathologic and clinical findings of
      patients presenting to the Department of Otolaryngology at the University of
      Mannheim, Germany. METHODS: From 2000 to 2004, 17 patients presented to our
      clinic with EACC. The cholesteatoma were treated surgically, and the specimens
      were investigated histologically. Clinical findings were also recorded. We
      classified four stages: stage I with hyperplasia of the canal epithelium, stage
      II including periosteitis, Stage III including a defective bony canal, and stage
      IV showing an erosion of adjacent anatomic structure. RESULTS: Eight patients
      presented with stage II, five patients with stage III, three with stage I, and
      only one patient presented with erosion of the mastoid cells, which was
      determined as stage IV. CONCLUSION: In summary, our classification serves to
      describe the different histopathologic and clinical stages of EACC.

PMID- 15744158
TI  - GJB2 mutations in hearing impairment: identification of a broad clinical spectrum
      for improved genetic counseling.
AB  - OBJECTIVES/HYPOTHESIS: Hearing impairment has a high prevalence affecting
      approximately 1 in 1000 newborn children. Alterations in the gap junction protein
      beta 2 (GJB2) and gap junction protein beta 6 (GJB6) are associated with
      nonsyndromic hearing impairment and should have a significant impact on genetic
      counseling. STUDY DESIGN: Various cases of nonsyndromic hearing impairment were
      screened for alterations in GJB2 and GJB6 in this clinical study. METHODS: The
      prevalence of mutations in GJB2 encoding for connexin 26 in a patient group with
      nonsyndromic hearing impairment comprising 45 families and 57 sporadic cases was
      initially determined by sequencing. The role of GJB2 was then assessed in
      individuals with hearing impairment (3 families and 20 sporadic cases) who are
      usually excluded from analysis because of the presence of additional symptoms or
      in cases in which a role for nongenetic factors cannot be eliminated. In hearing
      impaired individuals with heterozygous GJB2 mutations the recently identified 342
      kb deletion truncating GJB6 called del(GJB6-D13S1830) as a digenetic component in
      hearing impairment was excluded by polymerase chain reaction. RESULTS: Autosomal
      recessively inherited GJB2 mutations induced hearing impairment in 25.5% of
      individuals in the nonsyndromic hearing impairment group. GJB2 alterations were
      also seen in 17.4% of individuals in whom additional symptoms or a role for
      nongenetic involvement could not be excluded. In all, 15 different alterations in
      GJB2 were detected, including the previously unknown 154G>C, 557C>T, and 682C>T
      mutations, and these were correlated to clinical parameters. CONCLUSION: Improved
      genetic counseling can be performed by screening for GJB2 alterations in patients
      with nonsyndromic hearing impairment including patients within groups for which a
      role for exogenetic factors cannot be excluded. Specific genetic counseling for
      GJB2-linked hearing impairment in heterozygotes will depend on future research.

PMID- 15744159
TI  - Correlation between computed tomography scores and symptomatic improvement after
      endoscopic sinus surgery.
AB  - OBJECTIVES/HYPOTHESIS: The aim of the study was to determine the correlation
      between preoperative computed tomography scores and the improvement of symptom
      scores in patients treated with functional endoscopic sinus surgery. STUDY
      DESIGN: Retrospective analysis of prospectively collected data. METHODS:
      Retrospective analysis of prospectively collected data of patients undergoing
      functional endoscopic sinus surgery at a tertiary care medical center over a 2
      year period for rhinosinusitis refractory to medical therapy was performed.
      Computed tomography scans were graded according to the Lund-Mackay system.
      Patient symptom scores were recorded from the 20-item sinonasal outcome test
      (SNOT-20) inventory preoperatively and at 3, 6, and 12 months postoperatively.
      Correlation was assessed by the Pearson correlation coefficient (r). RESULTS: One
      hundred thirteen patients were identified with 1-year follow-up. The mean
      preoperative computed tomography grade was 13.2 with a mean SNOT-20 symptom score
      of 30.6. Preoperative CT scores did not correlate with preoperative symptom
      scores (r = 0.314). The SNOT-20 symptom scores improved 72%, 75%, and 77% at 3-,
      6-, and 12-month follow-up, respectively, from preoperative values. In addition,
      there was no correlation between preoperative computed tomography scores and
      percentage of improvement at 3-, 6-, and 12-month follow-up (r = -0.003, r = 
      0.015, and r = -0.059, respectively). CONCLUSION: The severity of rhinosinusitis
      on preoperative computed tomography scan does not predict the severity of
      symptoms as assessed by the SNOT-20 inventory in patients undergoing functional
      endoscopic sinus surgery. Further, computed tomography scores fail to predict the
      amount of symptomatic improvement after functional endoscopic sinus surgery.
      Patients receive a mean reduction in symptom scores of 77% after treatment with
      functional endoscopic sinus surgery.

PMID- 15744160
TI  - Incidence and significance of clinically unsuspected thyroid tissue in lymph
      nodes found during neck dissection in head and neck carcinoma patients.
AB  - OBJECTIVES/HYPOTHESIS: The objectives were to quantify the incidence of
      clinically unsuspected thyroid tissue in cervical lymph nodes encountered during
      neck dissection in patients with head and neck carcinoma, to describe the
      location and histological aspect of these inclusions, and to assess their
      clinical significance. STUDY DESIGN: Retrospective study. METHODS: The
      histological records of 1123 neck dissections in 752 patients with head and neck
      carcinoma were reviewed. In cases with thyroid inclusions, the pathological
      diagnosis was reviewed and an immunohistochemical study against thyroglobulin and
      calcitonin was carried out. RESULTS: Clinically unsuspected thyroid tissue was
      found in lymph nodes in 11 of the 752 patients with head and neck carcinoma
      treated with neck dissection. In five cases, the thyroid inclusion was compatible
      with a metastases of an occult papillary thyroid carcinoma. In the other six
      cases, a collection of thyroid follicles without malignant characteristics was
      found beneath the lymph node capsule. These latter cases were considered benign
      thyroid inclusions. A thyroidectomy was performed in three of the patients with
      lymph node metastases of the papillary carcinoma. An occult papillary carcinoma
      was found in only one case. The other two patients had been treated previously
      with radiotherapy for an early-stage glottic carcinoma. Immunohistochemical study
      did not find calcitonin-positive cells within the benign thyroid inclusions.
      After a follow-up period ranging from 1.2 to 8.2 years, no patient had any kind
      of local, regional, or distant relapse related to the thyroid disease.
      CONCLUSION: The incidence of unsuspected thyroid tissue in lymph nodes of
      patients with head and neck carcinoma treated with neck dissection was 1.5%. Both
      lymph node metastases of a papillary carcinoma and benign thyroid inclusions were
      found. The study results suggest that the incidental finding of thyroid tissue in
      the lymph nodes during a neck dissection in patients with head and neck carcinoma
      does not necessarily indicate the need for aggressive therapy.

PMID- 15744161
TI  - Morphological changes of the posterior airway space after tongue base suspension.
AB  - OBJECTIVES/HYPOTHESIS: The objectives were 1) to demonstrate the efficacy of
      tongue base suspension with the Repose System in modifying the posterior airway
      space on the basis of morphological changes in the retrolingual space and 2) to
      determine the implications of this procedure for the treatment of obstructive
      sleep apnea syndrome on polysomnographic and psychometric data. STUDY DESIGN: A
      prospective, nonrandomized study. METHODS: Polysomnography was performed before
      as well as 3 and 12 months after surgery in patients undergoing tongue base
      suspension using the Repose System. To identify morphological changes in the
      posterior airway space, lateral cephalometric radiography and videoendoscopy of
      the pharynx were performed preoperatively and postoperatively. Twenty-eight male
      patients with obstructive sleep apnea syndrome were included in the study. A
      suspension suture anchored intraorally at the mandible was passed submucosally in
      the body of the tongue, with suture tightness adjusted individually. RESULTS: The
      posterior airway space was widened by at least 2 mm in 60% of cases. Daytime
      sleepiness improved subjectively in 67% of patients, and the respiratory
      disturbance index improved postoperatively in 55%. The correlation between
      posterior airway space widening and the improvements in daytime sleepiness and
      respiratory disturbance index was not significant. CONCLUSION: Surgical
      intervention in obstructive sleep apnea syndrome with the Repose System does not
      result in permanent anatomical change in the posterior airway space.

PMID- 15744162
TI  - A new experimental model of acquired cholesteatoma.
AB  - OBJECTIVE: Cholesteatoma is a recurrent disease that is difficult control by
      otologists. This study aims to develop an experimental model of cholesteatoma
      that is easy to reproduce, using latex to induce the inflammatory reaction and
      propylene glycol as the foreign body in the middle ear. STUDY DESIGN: We used a
      new experimental model in which an intentional perforation was performed on the
      tympanic membrane of rats, followed by the introduction of a latex biomembrane.
      METHODS: A control group was submitted only to perforation of the tympanic
      membrane. Propylene glycol with latex was used in experimental group 1 and latex
      alone in experimental group 2. The rats were killed during the eighth week and
      their tympanic bullae were stained with hematoxylin and eosin. RESULTS: Eighty
      percent of the animals in group 1 and 90% in group 2 developed a cholesteatoma.
      No formation of cholesteatomas or inflammatory tissue occurred in the control
      group. CONCLUSION: The presence of inflammatory cells may provoke the production
      of cytokines (IL-1, IL-2, IL-6, IL-8) and growth factors, which, together with
      the latex biomembrane, which is known to contain a protein that favors vascular
      growth, may cause chemotactic migration of the squamous epithelium from the
      external auditory meatus to the middle year of the rat, causing a cholesteatoma.
      The induction of an experimental cholesteatoma in rats with latex and latex plus
      50% propylene glycol was effective, representing an excellent experimental model.
      The theory of epithelial migration in the genesis of cholesteatomas was confirmed
      by our observations in rats. The latex induced an acute and chronic inflammatory
      reaction when in contact with the mucosa of the middle ear.

PMID- 15744163
TI  - Is GERD a risk factor for laryngeal cancer?
AB  - OBJECTIVE/HYPOTHESIS: The significance of gastroesophageal reflux disease (GERD)
      in laryngeal cancer is controversial due to disparate studies. To evaluate the
      overall strength of the association of GERD with laryngeal cancer, we performed
      meta-analysis of the original studies in literature. STUDY DESIGN: Meta-analysis.
      METHODS: All studies cited on Ovid Medline (1966-June 2004), EMBASE (1980-June
      2004), and Cochrane database describing GERD and laryngeal cancer were eligible
      for inclusion. The inclusion criteria for the study included original controlled
      study design and a clear documentation of the reflux prevalence in cases and
      controls. Statistical analysis was performed by NCSS software. RESULTS: Fifteen
      original studies were identified. Eight studies did not have control groups, two
      studies did not clearly document GERD prevalence in controls, and two studies
      were published using the same data, one of which was included in this meta
      analysis. Thus, four studies qualified for inclusion for the meta-analysis. The
      methodologic quality in the studies was heterogeneous, not only in the evaluation
      of confounding risk factors such as smoking and alcohol but also in the mode of
      GERD diagnosis. There was also significant heterogeneity of effect of reflux
      among the studies (P = .001). The pooled odds ratio on the basis of fixed-effects
      model was 2.86 (95% CI, 2.73-2.99), and on the basis of random-effects model was
      2.37 (95% CI 1.38-4.08). CONCLUSION: Our meta-analysis suggests that GERD may be
      a significant risk factor for laryngeal cancer. However, given the heterogeneity
      of the published data, future prospective controlled studies are needed.

PMID- 15744164
TI  - Informed consent in endoscopic sinus surgery: the patient perspective.
AB  - OBJECTIVES: To understand patient expectations during the informed consent
      process for functional endoscopic sinus surgery (FESS). STUDY DESIGN: Multi
      institutional, cross-sectional survey design. METHODS: Anonymous surveys were
      administered to patients in two tertiary academic centers with a chief complaint
      relating to "allergy and sinus" problems. Patients completed an eight-item
      questionnaire that assessed both the nature and the level of risks that they
      wished to be informed of prior to FESS. RESULTS: Three hundred eighty-nine
      surveys were returned. Sixty-nine percent of patients wished to be informed of
      complications that occur as infrequently as 1 in 100 cases, regardless of
      severity. Ninety percent of patients wanted to know of a risk that occurred as
      frequently as 1 in 10 cases. Patients also reported whether or not they wished to
      be told in detail about specific complications during the informed consent
      process, regardless of their infrequency. Affirmative responses were as follows:
      83% for cerebrospinal fluid leak and orbital injury, 81% for infection, 76% for
      revision surgery, 74% for impairment of smell, 73% for bleeding and myocardial
      infarction, 72% for cerebrovascular accident, and 58% for scarring. CONCLUSIONS:
      Patients wanted to be informed about severe FESS complications at a higher rate
      than physicians previously surveyed, even if the incidence is low. This study,
      combined with our previous examination of the physicians' perspective, highlights
      that there may be a discrepancy between what the physician and the patient
      believe are priority topics during the informed consent process.

PMID- 15744165
TI  - Teaching emergency airway management using medical simulation: a pilot program.
AB  - OBJECTIVE: Simulation is a tool that has been used successfully in many high
      performance fields to permit training in rare and hazardous events. Our goal was
      to develop and evaluate a program to teach airway crisis management to
      otolaryngology trainees using medical simulation. METHODS: A full-day curriculum
      in the management of airway emergencies was developed. The program consists of
      three airway emergency scenarios, developed in collaboration between attending
      otolaryngologists and faculty from the Center for Medical Simulation. Following
      each scenario, the participants are led in a structured, video-assisted
      debriefing by a trained debriefer. Didactic material on team leadership and
      crisis management is built into the debriefings. Pediatric otolaryngology
      fellows, residents, and medical students have participated in the four courses
      that have been held to date. Participants evaluated the program on a five-point
      Likert scale. RESULTS: A total of 17 trainees participated in four pilot training
      courses. The survey data are as follows: overall program, 5.0 (SD, 0.00); course
      goals, 4.79 (SD, 0.43); realism, 4.36 (SD, 0.63); value of lecture, 4.71 (SD,
      0.47); and quality of debriefings, 4.92 (SD, 0.28). Sample comments include:
      "This is a valuable tool for students and residents since true emergencies in ORL
      are often life-threatening and infrequent," and "This is a great course-really
      all physicians should experience it." Overall evaluation was extremely positive
      and both residents and fellows described the course as filling an important void
      in their education. CONCLUSION: Medical simulation can be an extremely effective
      method for teaching airway crisis management and teamwork skills to
      otolaryngology trainees at all levels.

PMID- 15744166
TI  - Operative management of superior semicircular canal dehiscence.
AB  - OBJECTIVE: To assess the outcomes of patients undergoing surgical management of
      superior semicircular canal dehiscence (SSCD). STUDY DESIGN: Retrospective
      review. METHODS: The medical records of all patients undergoing surgical
      treatment for SSCD at our institution between 2000 and 2004 were reviewed.
      RESULTS: Eleven patients underwent unilateral operative management via a middle
      fossa approach. Ten patients were treated successfully by canal plugging and one
      unsuccessfully by canal re-roofing. Plugging of SSCD provided resolution of sound
      and pressure-induced nystagmus, autophony, and conductive hearing loss (HL). One
      patient experienced a mild high-frequency sensorineural HL and two patients
      experienced both a mild high-frequency sensorineural HL and a reduction in
      vestibular function. Two additional patients underwent exploration for SSCD but
      were found to have a thin layer of bone overlying the canal. CONCLUSIONS:
      Plugging of the SSCD, while efficacious in alleviating the symptoms of the
      disease, may cause loss of labyrinthine function beyond the superior canal.

PMID- 15744167
TI  - Detection of HCV-RNA in cerumen of chronically HCV-infected patients.
AB  - OBJECTIVES/HYPOTHESIS: Viral hepatitis C is a worldwide public health problem.
      Hepatitis C virus is mainly transmitted by parenteral or percutaneous route.
      Nonparenteral transmission, such as through sexual activity, household contact,
      and vertical or perinatal exposure to body fluids or secretions, can occur, which
      has been studied before. Cerumen, however, has not been investigated for its
      ability to transmit hepatitis C virus. The aim of this study is to evaluate the
      importance of cerumen in transmission of hepatitis C virus infection. STUDY
      DESIGN: This study was performed on 35 patients with confirmed chronic hepatitis
      C virus infection. METHODS: Thirty-five cerumen specimens collected from the
      patients with hepatitis C virus RNA in their sera were prospectively analyzed for
      the presence of hepatitis C virus RNA by polymerase chain reaction. RESULTS: None
      of the 35 cerumen specimens were positive for hepatitis C virus RNA. CONCLUSION:
      This study showed that cerumen has no risk for transmission of hepatitis C virus
      infection, even in patients with high hepatitis C virus RNA serum levels;
      however, standard infection control precautions should be applied carefully in
      all examinations and surgical operations of the ears.

PMID- 15744168
TI  - Nasal provocation testing as an international standard for evaluation of allergic
      and nonallergic rhinitis.
AB  - Standardized nasal provocation testing (NPT) has been shown to be a safe and very
      useful tool in the diagnosis of allergic and nonallergic rhinitis. However, in
      the United States, its use has been mostly limited to scientific investigations,
      and it has not yet been widely accepted as a standard diagnostic procedure in
      clinical practice. NPT aims to identify and quantify the clinical relevance of
      inhalant allergens or occupational irritants. During NPT, nasal respiratory
      mucosa is exposed to an airborne substance suspected to cause symptoms in the
      respective individual. Clinical reactions are monitored in a controlled and
      standardized fashion. Nasal secretions, symptoms such as itching, sneezing and,
      most importantly, nasal obstruction are assessed as well as ocular, bronchial,
      cutaneous, and systemic reactions. To achieve objective data on changes in nasal
      airflow and patency after the challenge, anterior rhinomanometry and acoustic
      rhinometry have been included in the standard protocol of NPT. By monitoring
      changes of nasal airflow on one hand and of nasal geometry on the other hand,
      these methods display nasal function in a graphic way just as speech and pure
      tone audiometry do for auditory function. Also, by their objective nature, these
      methods offer a clear and internationally comparable standard. This review
      outlines a protocol for NPT and discusses practical applications and clinical
      indications. The use of rhinomanometry and acoustic rhinometry as objective
      diagnostic tools is emphasized. For the diagnosis of allergic and occupational
      rhinitis, standardized NPT should be regarded as an international diagnostic
      standard.

PMID- 15744169
TI  - Effect of salivary fistulas on free flap failure: a laboratory and clinical
      investigation.
AB  - OBJECTIVES: Infection is associated with free flap failure in patients undergoing
      microvascular flap reconstruction. This study investigates the association
      between infection arising from salivary fistulas, microvascular thrombosis, and
      free flap failure. STUDY DESIGN: Prospective laboratory investigation and
      retrospective clinical investigation. METHODS: The effect of saliva-induced
      infection on the patency of microvascular thrombosis was studied in an
      experimental animal model and in a clinical series of patients undergoing free
      flap reconstruction of the head and neck. In the laboratory phase of this study,
      rat femoral artery anastomoses were inoculated with freshly collected rat saliva
      to simulate a postoperative salivary fistula. The incidence of femoral artery
      thrombosis was determined. In the clinical arm of this study, the incidence of
      salivary fistulas and resulting clinical outcome in 588 head and neck free flap
      reconstructions were examined. RESULTS: In the animal experiment, arterial
      patency was 95% after 10 days for both the control group and the salivary
      contamination group. In the clinical series, 24 patients developed salivary
      fistulas during the postoperative period. No cases of microvascular thrombosis
      were attributed to salivary fistula formation. CONCLUSIONS: Postoperative
      salivary fistulas do not appear to be strongly associated as a contributory
      factor toward free flap failure in head and neck reconstruction. On the basis of
      our current understanding of this condition, we describe a rational approach for
      management of patients who develop salivary fistulas after microvascular head and
      neck reconstruction.

PMID- 15744170
TI  - Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma
      of the head and neck patients.
AB  - OBJECTIVE: Our objective was to characterize cytokine profiles in the systemic
      circulation of patients with active squamous cell carcinoma of the head and neck
      (SCCHN) compared with long-term tobacco smokers as controls. Furthermore, we
      hypothesized that persistent immune dysregulation in patients cured of their
      disease may be reflected in altered cytokine profiles in the systemic
      circulation. STUDY DESIGN: Retrospective, case-control study. METHODS: Using
      three well-defined clinical cohorts of SCCHN patients and smoker controls, we
      analyzed 100 microL of serum for a panel of 10 cytokines to determine whether
      serum cytokine profiles could distinguish clinically defined groups of SCCHN
      patients. Statistical analysis of multiplexed cytokine profiles was applied to
      classify three clinically defined groups: active SCCHN patients, treated SCCHN
      patients with no evidence of disease for over 3 years, and matched disease-free
      controls. Discrimination of outcome status was accomplished using classification
      trees, and 10-fold cross-validation was implemented to assess classification
      accuracy using independent data. RESULTS: We show that multiplexed cytokine and
      chemokine profiling may be performed to reflect the immune status of SCCHN
      patients. Selected cytokine profiles indicate that immunologic responses to
      carcinogenesis may not normalize even in the absence of tumor for over 3 years.
      CONCLUSION: Multiplexed serum cytokine profiles may be applicable to early
      detection, for screening those at high risk for SCCHN, and as clinically
      predictive biomarkers of disease status in successfully treated patients.

PMID- 15744171
TI  - Bipedicled strap muscle transposition for vocal fold deficit after laser
      cordectomy in early glottic cancer patients.
AB  - OBJECTIVE: In treating early glottic carcinomas, the outcomes of endoscopic laser
      cordectomy have been proven to be valuable in local control, survival, and vocal
      function preservation. In some extended cases, however, laser cordectomy may
      leave patients with poor vocal function because of vocal fold deficit. This work
      assesses the vocal outcome of medialization laryngoplasty with bipedicled strap
      muscle transposition for vocal fold deficit resulting from laser cordectomy in
      early glottic cancer patients. STUDY DESIGN: A prospective clinical series.
      METHODS: Thirteen early glottic cancer patients who had vocal fold deficit caused
      by previous laser cordectomy underwent medialization laryngoplasty with
      bipedicled strap muscle transposition. The thyroid lamina on the cordectomy side
      was paramedially separated. The inner perichondrium was circumspectly raised from
      the overlying thyroid cartilage. After separating the thyrohyoid and cricothyroid
      membranes, the lamina was retracted laterally. A bipedicled strap muscle flap was
      then transposed into the area between the lamina and the paraglottic soft tissue.
      The thyroid cartilages were carefully sutured back in position. All patients
      received pre- and postoperative voice assessments comprising laryngostroboscopy
      and vocal function studies. RESULTS: Vocal enhancement was present in 92% (12/13)
      of patients after medialization laryngoplasty with strap muscle transposition.
      The glottal closure and maximal phonation time were noticeably improved by
      surgery. No dyspnea or other significant complications were observed in any
      patients. CONCLUSION: The outcomes show that bipedicled strap muscle
      transposition is a prosthesis-free, safe, and valuable laryngoplastic technique
      for correcting glottal incompetence caused by endoscopic laser cordectomy in
      early glottic cancer patients.

PMID- 15744172
TI  - Tracheal climate in laryngectomees after use of a heat and moisture exchanger.
AB  - OBJECTIVE/HYPOTHESIS: Heat and moisture exchangers (HME) are frequently used in
      the treatment and prevention of tracheobronchial dryness and infections. In this
      study, the short-term influence of the HME Prim-Air System (Heimomed, Kerpen,
      Germany) in laryngectomized patients was tested. STUDY DESIGN: Prospective study.
      METHODS: After adaptation to the laboratory environment, tracheal humidity and
      temperature were measured before HME application, 1 minute after HME application,
      10 minutes after HME application, 1 minute after removal of the HME, and 10
      minutes after removal of the HME. RESULTS: When the HME was placed on the
      tracheal stoma, the end-inspiratory humidity and temperature increased
      significantly. Ten minutes after commencement of use of the HME, tracheal
      humidity further increased significantly. Ten minutes after removal of the HME,
      tracheal humidity and temperature decreased to values as before start of use of
      HME. CONCLUSIONS: The results indicate that short-term use of the HME Prim-Air
      system rapidly changes the tracheal climate. The significant increase in tracheal
      temperature and humidity may have beneficial effects on tracheal dryness in
      laryngectomized patients.

PMID- 15744173
TI  - Validity of sleep nasendoscopy in the investigation of sleep related breathing
      disorders.
AB  - OBJECTIVE: To validate the technique of sleep nasendoscopy using target
      controlled infusion in symptomatic patients and a control group of asymptomatic
      individuals. DESIGN: Prospective cohort study. SETTING: Department of
      otolaryngology-head and neck surgery and anesthesia in a teaching hospital.
      PARTICIPANTS: Two groups of patients were compared and matched for their body
      mass index. The first group consisted of 53 patients with a history suggestive of
      obstructive sleep apnea. The second group consisted of 54 patients with partner
      confirmed history of no snoring. These patients were undergoing anesthesia for
      other reasons. Both groups of patients were free of associated
      otorhinolaryngologic symptoms. MAIN OUTCOME MEASURE: Assessment of production of
      snoring or obstruction in patients with no documented history of snoring when
      sedation was administered as part of general anesthesia using target controlled
      infusion with propofol. RESULTS AND CONCLUSIONS: None of the patients in the
      asymptomatic group snored or obstructed at any level of propofol, and this was
      clearly significant on comparison with the symptomatic group (P < .001). All of
      the symptomatic patients were induced to become symptomatic
      (snoring/obstruction).

PMID- 15744175
TI  - Acoustic and aerodynamic measurement of speech production after supracricoid
      partial laryngectomy.
AB  - BACKGROUND: Supracricoid partial laryngectomy (SCPL) results in laryngeal
      preservation in more than 95% of patients with T2 glottic carcinoma. After
      surgery, glottis function is characterized by an absence of vocal cords and poor
      glottis closure. Voice is an important postSCPL quality of life factor.
      OBJECTIVE: Enhance postSCPL vocal function. Obtain postsurgical acoustic and
      aerodynamic measurements and correlate multiple objective parameters with
      perceptual results. METHOD: Continuous speech voice samples from 61 patients who
      had undergone SCPL more than 1 year before were scored according to the global,
      roughness, breathiness, asthenia, and strain (GRBAS) scale by a jury of
      listeners. Acoustic and aerodynamic parameters were recorded: fundamental
      frequency (F0), intensity, jitter, shimmer, signal-to-noise ratio (SNR), signal
      to-noise ratio greater than 1 kHz (SNR>1), oral airflow (OAF), maximum phonation
      time (MPT), and estimated subglottic pressure (ESGP). Nonparametric tests and
      logistic regression analysis were used to compare objective measurements and
      perceptual evaluations. RESULTS: All patients had various degrees of dysphonia:
      grade 1, 4.9%; grade 2, 55.7%; and grade 3, 39.4%. Correlations between
      perceptual grades and objective parameters were obtained for jitter, shimmer,
      SNR, SNR>1, ESGP, and OAF. No correlations were obtained between the different
      parameters and age, number of arytenoids, and time elapsed since surgery (TESS).
      Logistic regression analysis of jitter, SNR, ESGP, and OAF parameters revealed
      92.6% agreement with the perceptual evaluation results.

PMID- 15744174
TI  - Sialoendoscopic and irrigation findings in chronic obstructive parotitis.
AB  - OBJECTIVES/HYPOTHESIS: To study the sialographic changes related to
      sialoendoscopic and irrigation fluid findings in chronic obstructive parotitis.
      STUDY DESIGN: The sialographic changes were classified according to previous
      studies and related to sialoendoscopic and irrigation fluid findings. METHODS:
      This study included 26 patients with a long history of parotid swelling. All
      patients were examined by radiography and sialography and were diagnosed as
      having chronic obstructive parotitis without sialolithiasis. Sialoendoscopy was
      used to observe the ductal system and perform an irrigation treatment. The
      irrigated liquid was centrifuged, and the fluid deposits were stained and
      observed using light microscopy. RESULTS: In all cases, sialoendoscopic
      examination showed the ductal system was filled with fiber-like substances and
      hyperemia of the ductal wall. Although a few of the thin and short fiber-like
      substances were found in the chronic obstructive parotitis patients with
      sialographic type I and type II changes, many thick and long wadding or lumpy
      fiber-like substances were revealed in chronic obstructive parotitis patients
      with sialographic type III and IV changes. Microstones were found in two chronic
      obstructive parotitis patients with sialographic type III changes, which were
      stained and identified using light microscopy. Irrigation fluid examination
      showed that the fiber-like substance was composed of desquamative duct epithelial
      cells, neutrophils, lymphocytes, and acidophils. Also, some epithelial cells were
      found in two microliths. CONCLUSIONS: Sialoendoscopy can provide direct and more
      detailed observation of the ductal system compared with sialography. Fiber-like
      substances in the lumen of the ductal system are considered one of the
      obstructive factors associated with chronic obstructive parotitis.

PMID- 15744177
TI  - External auditory canal translocation for cochlear implantation.

PMID- 15744176
TI  - Delivery of cidofovir to respiratory papillomas of the distal trachea.

PMID- 15744178
TI  - The acetabular reamer: a unique tool for anterior iliac crest bone graft
      harvesting.
AB  - Bone grafting is often required in craniofacial reconstruction. Morselized
      corticocancellous bone grafts are particularly useful in applications such as
      filling and contouring irregular bony defects. Obtaining grafts of this
      consistency by traditional methods is difficult. An efficient harvesting method
      that can produce such grafting material in clinically useful quantities is
      needed. We report the use of a mechanical acetabular reamer for the purpose of
      harvesting a bone graft from the iliac crest.

PMID- 15744180
TI  - Is your case report really an invasive fungal rhinosinusitis?

PMID- 15744181
TI  - Is your case report really an invasive fungal rhinosinusitis?

PMID- 15744185
TI  - Menopause: hormone therapy & other options.

PMID- 15744183
TI  - Preventing and treating: heart disease in women.
AB  - More women than men die of heart disease, yet a woman's heart disease symptoms
      are more likely to be overlooked. Learn how to recognize heart disease in women
      and help them get the treatment they need.

PMID- 15744186
TI  - Abnormal vs. dysfunctional uterine bleeding: what's the difference?
AB  - Sort out the differences between uterine bleeding that's abnormal and that which
      is dysfunctional. Then teach your patient about new treatments that are available
      for these sometimes-dangerous conditions.

PMID- 15744187
TI  - Putting the squeeze on venous ulcers.
AB  - Compression is still the cornerstone of treatment for these common wounds. Learn
      how to choose the right product for your patient.

PMID- 15744188
TI  - What to see and do in San Diego.

PMID- 15744189
TI  - Off the beaten track...Online.

PMID- 15744191
TI  - Electrocardiogram interpretation and management in a pediatric emergency
      department.
AB  - OBJECTIVES: To determine the accuracy of electrocardiogram (ECG) interpretation
      by pediatric emergency physicians through comparison with a pediatric
      cardiologist and to determine the intrarater and interrater reliability for
      pediatric emergency physicians and cardiologists. METHODS: This was a prospective
      cohort study in which pediatric emergency physicians ordering an ECG completed a
      standardized questionnaire. The same emergency physician, a second emergency
      physician, and a pediatric cardiologist also completed the questionnaire for all
      ECGs at a later time. A randomly selected subset of ECGs was also interpreted by
      the same cardiologist and a second pediatric cardiologist. Major outcome
      variables were (1) whether the ECG was normal or abnormal, and if abnormal, (2)
      whether the abnormality represented a minor or major concern, and (3) whether the
      ECG warranted referral to a pediatric cardiologist. RESULTS: For pediatric
      emergency physicians, the intrarater and interrater kappa values were 0.56 and
      0.24 for the presence of an abnormality, 0.49 and 0.36 for level of concern, and
      0.63 and 0.25 for need of cardiology follow-up. For pediatric cardiologists, the
      intrarater and interrater kappa values were 0.82 and 0.92 for the presence of an
      abnormality, 0.71 and 1.00 for level of concern, and 0.82 and 0.91 for need of
      cardiology follow-up. A comparison of the initial emergency physician and
      cardiologist interpretations yielded kappa values of 0.42 for the presence of an
      abnormality, 0.16 for level of concern, and 0.31 for need of cardiology follow
      up. CONCLUSIONS: When compared with interpretation by a pediatric cardiologist,
      ECG interpretation by pediatric emergency physicians was relatively inaccurate;
      intrarater and interrater agreement among emergency physicians was good and poor,
      respectively, and the intrarater and interrater agreement among pediatric
      cardiologists was excellent.

PMID- 15744192
TI  - Acute brain perfusion disorders in children assessed by quantitative perfusion
      computed tomography in the emergency setting.
AB  - OBJECTIVE: Perfusion computed tomography (CT) is a simple imaging technique that
      allows accurate quantitative assessment of brain perfusion. Perfusion CT is an
      ideal imaging technique to be used in the emergency setting and has thus gained
      recognition in the early management of adult acute stroke patients. Perfusion CT
      can be applied to children successfully by using adequate imaging protocols. The
      goal of this article is to provide a pictorial essay of the perfusion CT features
      of diseases that affect brain perfusion as depicted in a population of children
      who were evaluated in the emergency CT unit of our institution. METHODS: During
      the period of September 2001 to October 2002, all the children, who were
      evaluated in the emergency CT unit of our institution and who were prescribed
      with a cerebral CT and an intravenous administration of iodinated contrast
      material, underwent a perfusion-CT examination. Perfusion-CT maps were reviewed
      in the patients diagnosed as abnormal on the basis of follow-up
      clinical/radiological examinations and correlated with the results of these
      tests. RESULTS: Brain perfusion-CT examinations have been performed in 77
      children. Fifty-three patients were considered as normal, based on normal
      conventional cerebral CT and normal clinical/radiological follow-up. Perfusion-CT
      results showed major abnormalities in 14 cases among the 24 remaining patients,
      related to brain ischemia in 2, head trauma in 9, brain infection in 2, and
      sickle cell disease in 1. These abnormalities consisted in low regional cerebral
      blood flow and volume values, and in high mean transit time values. They
      demonstrated typical anatomical distribution, depending on the considered
      pathological condition. CONCLUSIONS: Perfusion CT provides quantitative
      assessment of child brain perfusion disorders. Its ability to be easily performed
      upon admission makes it an ideal emergency tool that advantageously competes with
      other imaging techniques such as perfusion-weighted magnetic resonance imaging,
      despite its limited spatial coverage. Its usefulness with respect to the impact
      on treatment and outcome, however, remains to be established in further studies.

PMID- 15744193
TI  - Factors predicting early diagnosis of foreign body aspiration in children.
AB  - OBJECTIVES: To analyze the clinical spectrum of tracheobronchial foreign bodies
      in children and explore the clinical features which could facilitate early
      diagnosis. METHODS: We retrospectively studied pediatric patients who had
      aspirated foreign bodies over the past 5 years from July 1998 to July 2003 in a
      tertiary children hospital in northern Taiwan. Patients were divided into 2
      groups according to the elapsed time from aspiration to definite diagnosis as
      early (< or =24 hours after aspiration) and late diagnosis (>24 hours after
      aspiration). The 2 groups were compared for clinical features, radiological
      findings, and the influence of morbidity and mortality of early- and late
      diagnosed foreign body aspiration (FBA). RESULTS: A total of 53 patients (27
      boys, 26 girls) were recruited with a median age of 25.4 +/- 21.3 months. FBA was
      suspected by the parents in 59% of patients. Sudden onset of cough (72%), dyspnea
      (64%), and wheeze (60%) were the predominant symptoms and signs. Nuts and peanut
      (59%) were the most common foreign bodies aspirated. Obstructive emphysema (53%)
      and normal chest radiograph (34%) were the most frequent radiological findings.
      Parenchymal consolidation with pneumonia was predominant in the group of late
      diagnosis (P < 0.05). Bronchial asthma (n = 9), pneumonia (n = 8), and common
      cold (n = 5) were the most common mistaken diagnoses. Witnessing of choking
      episode was the most important historical event to pinpoint an early diagnosis of
      FBA in children (P = 0.002). CONCLUSIONS: In children with an unequivocal choking
      event while eating even with normal physical and radiographic findings, FBA
      requires to be excluded by thorough investigations in such instances. Similarly,
      in toddlers with unexplained persistent cough with refractory parenchymal
      infiltrates, unrecognized FBA should also be considered. A witnessed choking
      event is the most important historical information to make an early diagnosis of
      FBA.

PMID- 15744194
TI  - Epidemiology and etiology of malpractice lawsuits involving children in US
      emergency departments and urgent care centers.
AB  - OBJECTIVE: To obtain epidemiologic outcome information about pediatric lawsuits
      that originate in the emergency department and urgent care center. METHODS: This
      was an anonymous retrospective review of all closed pediatric claims in the
      Physician Insurers Association of America database during a 16-year period (1985
      2000). This database, containing data from 20 major malpractice insurance firms,
      insuring 25% US physicians, was queried for epidemiologic outcome information
      about pediatric lawsuits originating in US emergency departments and urgent care
      centers. RESULTS: There were 2283 closed claims reviewed. Of these, 96%
      originated in the emergency department, and 4% originated in an urgent care
      center. Nonteaching hospitals were the sites for 79% of claims. Suits involved
      emergency department physicians in 29%, pediatricians in 19%, board-certified
      physicians in 46%, US graduates in 70%, and full-time physicians in 96% of cases.
      In 66% of cases, doctors had a previous claim. In 65% of cases, more than 1
      defendant was involved. Patients were boys in 59% and were younger than 2 years
      in 47%. The most common diagnoses involved in the lawsuits were meningitis,
      appendicitis, arm fracture, and testicular torsion. Cases in which the child died
      were most often from meningitis or pneumonia. The most common misadventures were
      diagnostic error (39%), and no medical error identified in 18%. OUTCOME: Cases
      were settled in 93% (indemnity paid in 30%). There was a judgment for the doctor
      in 5.5% and for the patient in 1.4%. The average indemnity/claim was US66,000
      dollars in 1985 versus US218,000 dollars (+330%) in 1997. The average indemnity
      ranged from US7000 dollars for emotional injury, US149,000 dollars for death of
      the patient, US300,000 dollars for major permanent injury, and US540,000 dollars
      for quadriplegic from injury. There was no significant difference between
      teaching versus nonteaching hospitals, between urgent care center versus
      emergency department, US graduate physician versus non-US graduate, or physician
      age. Indemnity paid/claim for full-time physicians was US161,000 dollars versus
      US91,000 dollars for part-time physicians. Total paid to plaintiffs was US116
      million dollars. Legal cost of defending the cases was US36 million dollars
      (including defense attorney fees, US24 million dollars, and expert witness fees,
      US3.4 million dollars). CONCLUSIONS: Malpractice suits most often involved
      fractures, meningitis, and appendicitis. Most suits are settled; many are
      apparently frivolous. Paid indemnities have dramatically increased in recent
      years. Verdicts decided by juries favored the doctor in 80% of suits.

PMID- 15744195
TI  - Reaction toward a new treatment paradigm for acute otitis media.
AB  - OBJECTIVE: Recent evidence suggests that oral antibiotics may not be required in
      all children with acute otitis media (AOM). We determined whether parents and
      pediatricians were aware of and comfortable with a policy of selective use of
      antibiotics for AOM. METHODS:  DESIGN: Descriptive survey. SETTINGS: Suburban
      academic emergency department, urgent care center, and private pediatric
      practices. PARTICIPANTS: Parents of children presenting to an emergency
      department and urgent care center and pediatricians in faculty and private
      practice. INTERVENTIONS AND OUTCOMES: Parents were asked whether they were aware
      of any side effects associated with antibiotic use or of research that supports
      selective use of antibiotics for AOM. Physicians were queried regarding the
      methods used to diagnose AOM and their patterns of prescribing antibiotics for
      AOM. Parents and physicians were questioned regarding their comfort with
      withholding antibiotics for AOM using a 6-point Likert scale ranging from very
      uncomfortable to very comfortable. RESULTS: Six hundred fifty-four parents and 84
      physicians were surveyed. Sixty-one percent of parents were unaware of the
      potential side effects of antibiotics, and 72% were unaware of research
      supporting selective use of antibiotics. Fifty-three percent of parents and 73%
      of physicians were somewhat comfortable to very comfortable with an observation
      option for AOM. Half of all pediatricians stated that they always prescribe
      antibiotic for AOM. CONCLUSIONS: Although most parents are unaware of selective
      use of antibiotics and half of all surveyed pediatricians stated that they always
      prescribed antibiotics for AOM, many parents and pediatricians felt comfortable
      with selective use of antibiotics.

PMID- 15744196
TI  - Rattlesnake envenomation to the face of an infant.
AB  - BACKGROUND: Mortality from rattlesnake envenomation in the United States is rare.
      Despite approximately 8000 crotaline (pit vipers) bites annually, it is estimated
      that only 10 to 15 deaths occur. Besides direct intravascular envenomation and
      anaphylaxis, bites to the head and neck may account for some of these rare
      fatalities. We report a pediatric case of severe facial envenomation requiring
      emergent intubation and antivenom administration. CASE REPORT: A 14-month-old
      female toddler was envenomated by a Southern Pacific rattlesnake (Crotalus
      viridis helleri) above the right upper lip while playing in her backyard. Rapid
      swelling and ecchymosis developed, and the patient was airlifted to a pediatric
      tertiary care hospital. Within 3 hours, stridorous respirations complicated by
      significant facial and oropharyngeal edema necessitated emergent orotracheal
      intubation. A total of 16 vials of FabAV [Crotalidae Polyvalent Immune Fab
      (ovine) antivenom] were administered over the next 24 hours. The child gradually
      improved and was successfully extubated 5 days later. A 3-month follow-up
      demonstrated no significant cosmetic facial abnormalities. CONCLUSION: Crotaline
      bites to the head and neck have the potential for significant swelling and airway
      compromise. Facial bites, anaphylaxis, and rare intravascular envenomation may
      account for many of the fatalities from rattlesnake envenomation. Early
      intubation may be required to maintain airway patency.

PMID- 15744197
TI  - Severe systemic reaction to Loxosceles reclusa spider bites in a pediatric
      population.
AB  - OBJECTIVE: To report 6 children who had severe systemic reaction after spider
      bites requiring pediatric intensive care unit admission and to describe their
      clinical presentation, hospital course, and outcome. METHODS: A retrospective
      analysis was done to identify patients presenting with brown recluse spider
      bites. Charts of children admitted to the intensive care unit were reviewed.
      RESULTS: Six previously healthy African-American children, aged 3 to 15 years,
      with brown recluse spider bites were admitted to the pediatric intensive care
      unit. All had fever, jaundice, and evidence of hemolytic anemia. Four of 6
      children had hypotension. One child developed mental status changes, acute renal
      failure secondary to rhabdomyolysis, and hyperkalemia and required emergent
      hemodialysis. All children fully recovered. CONCLUSION: Although most cases of
      brown recluse spider bites are benign requiring no intervention, severe systemic
      reactions may occur in the pediatric population resulting in admission to the
      pediatric intensive care unit. These systemic reactions may include hemolytic
      anemia, hypotension, and renal failure.

PMID- 15744198
TI  - Tibial fractures possibly linked to use of a baby stationary activity center.

PMID- 15744199
TI  - Evaluation and management of illness in a child after international travel.
AB  - International travel by children is becoming increasingly common over the last
      few decades. As a result, clinicians may be asked to assist in the evaluation and
      treatment of an ill child after international travel. Along with recording the
      typical thorough history of present illness and medical history, the physician
      who cares for a child in this situation will have to take a thorough travel
      history and consider not only local conditions, but also possible pathogens that
      the child may have encountered during the journey. A detailed travel history
      should be routinely performed to investigate specific exposures. Reference
      materials are available that can guide the clinician in determining which
      infectious agents are endemic to various areas of the world. With the exception
      of obtaining a basic laboratory screen, further evaluation of the young patient
      should be dictated by the most likely cause of the illness. Repeated testing and
      examinations and close follow-up may be necessary to arrive at the proper
      diagnosis and initiate appropriate treatment in a timely manner.

PMID- 15744200
TI  - Observation medicine: the expanded role of the nurse practitioner in a pediatric
      emergency department extended care unit.
AB  - BACKGROUND: The use of observational units (OUs) in pediatric emergency
      departments (EDs) has become an important adjunct to emergency care. An extended
      observation period (4 to 23 hours) in the ED has decreased both the number of
      admissions and prolonged use of acute ED beds. This serves to increase patient
      satisfaction as well as optimizing care. The use of OUs allows for the most
      appropriate allocation of resources. These units are typically located within the
      ED or immediately adjacent to it. The ED physicians are the gatekeepers of the
      unit and serve as the medical supervision for these patients. The Children's
      Hospital of Philadelphia developed an OU known in the hospital as the Emergency
      Department Extended Care Unit (EDECU) approximately 5 years ago. In order for the
      EDECU to function at its fullest potential, the ED at The Children's Hospital of
      Philadelphia has opted to use the ED nurse practitioners (NPs) to enhance the
      care for these patients. OBJECTIVE: The NP has been an integral member of the ED
      for the past 10 years with primary roles in urgent care and in the follow-up
      program. As the ED expanded to include the EDECU, the role of the NP also
      developed to meet the needs of these patients. A review of the role development
      of the ED NP in observation medicine and the impact on patient and staff
      satisfaction as well as contributing to fiscally responsible care will be
      addressed. METHODS: A retrospective review of the NP's role development in the
      evolution of the EDEDU. RESULTS: Incorporation of the NP in the treatment team
      has provided efficient use of professional staff, comprehensive patient care, and
      increased patient satisfaction. CONCLUSIONS: The use of the EDECU has become an
      important part of the services offered in the ED at The Children's Hospital of
      Philadelphia. The integration of the NP in a pivotal role allows for optimal use
      of human resources, and provides efficient, cost-effective patient care in the
      ED.

PMID- 15744201
TI  - Roller-skating: fell on wrist and now pain.

PMID- 15744202
TI  - Case Records of Wright State University. Febrile, stiff neck.

PMID- 15744203
TI  - A toddler with obtundation and miosis.

PMID- 15744204
TI  - Pediatric emergency medicine: legal briefs.

PMID- 15744205
TI  - ECGs in the ED.

PMID- 15744206
TI  - Response to shortcut dosing of acetaminophen and Ibuprofen.

PMID- 15744207
TI  - Timing and the rhythm of the mind.

PMID- 15744209
TI  - The rage to know, the rage to teach, and the rage to heal: what is the proper
      balance?

PMID- 15744208
TI  - Towards a neurology of aesthetics.

PMID- 15744210
TI  - Medical chronobiology in psychiatry and neurology.

PMID- 15744211
TI  - Circadian rhythms in medicine.
AB  - Circadian (24-hour) rhythms are important to the practice of medicine. The
      phasing and amplitude of key physiologic and biochemical circadian rhythms
      contribute to predictable-in-time patterns in the manifestation and exacerbation
      of most medical conditions. Moreover, body rhythms can significantly affect
      responses of patients to diagnostic tests and medications. Rhythmicity in the
      pathophysiology of medical conditions is the rationale for chronotherapeutics-
      the purposeful variance of the concentration of medicines in synchrony with
      biological rhythm--determinants of disease activity--to optimize treatment
      outcomes. This article discusses the concept of biological time structure and its
      relevance to the practice of medicine, with a focus on neurologic issues.

PMID- 15744212
TI  - Is seasonal affective disorder a disorder of circadian rhythms?
AB  - Seasonal affective disorder (SAD) is a form of depression that starts in the fall
      and ends in the spring. This article reviews existing theories about the
      relationship between circadian rhythms and the disorder. Recent research
      indicates that as with pharmacologic antidepressants, at least 2-4 weeks are
      needed to demonstrate the effectiveness of bright-light therapy compared to
      placebo. The response to such treatment is strongest with precisely timed light
      exposure: treatment is optimal during the morning hours when the circadian system
      is susceptible to phase advance. Such clinical improvement is correlated with the
      magnitude of the phase shift induced. These observations suggest a model of
      circadian function in SAD and provide important guidelines for its treatment.

PMID- 15744213
TI  - Melatonin rhythm abnormalities and sleep disorders in the elderly.
AB  - Biological aging is often associated with sleep problems and daytime napping.
      Complaints of difficulty in initiating and maintaining sleep, as well as daytime
      drowsiness, are more common in the elderly than in any other age group. This
      report reviews evidence that impaired melatonin secretion is associated with
      sleep disorders in old age. Circulating melatonin levels have been found to be
      significantly lower and onset and peak times have been delayed in elderly
      insomniacs as compared to age-matched control subjects. In view of these
      findings, we investigated the effects of melatonin treatment on melatonin
      deficient insomnia in the elderly. From the results of our study, it seems likely
      that melatonin replacement therapy may be beneficial in the initiation and
      maintenance of sleep in this population.

PMID- 15744214
TI  - The effect of smoking on brainstem auditory evoked potentials in positive- and
      negative-symptom schizophrenia.
AB  - Studying brainstem auditory evoked potentials (BAEPs) and comparing the specific
      waves in smokers vs nonsmokers in both positive- and negative-symptom
      schizophrenia may elucidate the role of smoking in information processing. BAEPs
      were recorded in 40 patients with schizophrenia; 20 had predominantly positive
      symptoms (10 smokers and 10 nonsmokers) and 20 had predominantly negative
      symptoms (10 smokers and 10 nonsmokers). The severity of positive and negative
      symptoms was assessed by scale of assessment of positive symptoms and scale of
      assessment of negative symptoms (SANS). The BAEP results were compared with 15
      healthy control individuals matched with the patients by age, sex, and cultural
      background. The smokers with negative symptoms showed a significant increase in
      the alogia, summary, and composite scores of SANS as compared to the nonsmokers.
      Although, most of the BAEP abnormalities were among patients with positive
      symptoms. The effect of smoking on the BAEPs was only in patients with negative
      symptoms. We also studied the interaction between smoking factor (smokers vs
      nonsmokers) and group type (group with mostly positive symptoms vs group with
      mostly negative symptoms) on the BAEPs and found a significant difference only
      for the first-wave latency mainly on the right side (P=0.012). The absence of a
      significant effect of smoking on most of the parameters of the BAEPs on
      interaction with the group factor suggests that the effect of smoking on the
      BAEPs is more apparent when negative symptoms prevail. However, studies are
      warranted to substantiate this finding.

PMID- 15744215
TI  - Circadian rhythm sleep disorders as a possible side effect of fluvoxamine.
AB  - Sleep problems, day somnolence, and fatigue as a result of psychotropic drugs are
      very common. Psychiatrists usually consider these effects a result of insomnia
      and treat them by prescribing sleeping pills or other benzodiazepine agents. We
      describe here 10 cases of circadian rhythm sleep disorders (CRSD)--and not merely
      insomnia--as a possible side effect of fluvoxamine (FVA). Two other serotonin
      reuptake inhibitors, fluoxetine and clomipramine, did not induce CRSD in any of
      these 10 patients. We speculate that FVA-induced CRSD is caused by the effect of
      FVA on serotonin and melatonin levels in the central nervous system. CRSD as a
      side effect of FVA can be treated by replacing the suspected FVA or adding
      melatonin to a beneficial FVA treatment. Thus, it is important to be aware of
      possible iatrogenic CRSD in order to treat appropriately. Prospective studies are
      needed to confirm our observation and to study the influence of other
      psychotropic drugs on sleep-wake schedule.

PMID- 15744217
TI  - Interactive case conference. Double depression.

PMID- 15744218
TI  - Ziprasidone as an augmenting agent in the treatment of anxiety-spectrum
      disorders.
AB  - Anxiety disorders are currently one of the most common health concerns in the
      United States. Overall, they are the single largest cost to the healthcare
      system. They are also underdiagnosed and undertreated. Selective serotonin
      reuptake inhibitors and benzodiazepines appear to be the most common
      pharmacologic treatment approaches. Unfortunately, not all patients respond to
      these treatments. Many augmentation strategies have been tried in the past with
      varying levels of success or safety. This article describes a safe and highly
      effective augmentation technique in patients suffering from some of the most
      serious and debilitating forms of anxiety disorders, namely obsessive-compulsive
      disorder and panic disorder.

PMID- 15744219
TI  - Understanding through animal models.

PMID- 15744220
TI  - Social stress in tree shrews as an animal model of depression: an example of a
      behavioral model of a CNS disorder.
AB  - Animal models are invaluable in preclinical research on human psychopathology.
      Valid animal models to study the pathophysiology of depression and specific
      biological and behavioral responses to antidepressant drug treatments are of
      prime interest. In order to improve our knowledge of the causal mechanisms of
      stress-related disorders such as depression, we need animal models that mirror
      the situation seen in patients. One promising model is the chronic psychosocial
      stress paradigm in male tree shrews. Coexistence of two males in visual and
      olfactory contact leads to a stable dominant/subordinate relationship, with the
      subordinates showing obvious changes in behavioral, neuroendocrine, and central
      nervous activity that are similar to the signs and symptoms observed during
      episodes of depression in patients. To discover whether this model, besides its
      "face validity" for depression, also has "predictive validity," we treated
      subordinate animals with the tricyclic antidepressant clomipramine and found a
      time-dependent recovery of both endocrine function and normal behavior. In
      contrast, the anxiolytic diazepam was ineffective. Chronic psychosocial stress in
      male tree shrews significantly decreased hippocampal volume and the proliferation
      rate of the granule precursor cells in the dentate gyrus. These stress-induced
      changes can be prevented by treating the animals with clomipramine, tianeptine,
      or the selective neurokinin receptor antagonist L-760,735. In addition to its
      apparent face and predictive validity, the tree shrew model also has a "molecular
      validity" due to the degradation routes of psychotropic compounds and gene
      sequences of receptors are very similar to those in humans. Although further
      research is required to validate this model fully, it provides an adequate and
      interesting non-rodent experimental paradigm for preclinical research on
      depression.

PMID- 15744221
TI  - Psychostimulant-induced behavior as an animal model of obsessive-compulsive
      disorder: an ethological approach to the form of compulsive rituals.
AB  - Rats treated chronically with the D2/D3 dopamine receptor agonist quinpirole show
      a pattern of behavior that meets a set of ethologically derived criteria of
      compulsive behavior in obsessive-compulsive disorder (OCD). Moreover, in both
      quinpirole-treated rats and OCD patients, the structure of compulsive rituals
      appear similar in being composed of relatively few motor acts that are organized
      in a flexible yet recurrent manner. In addition, the development of compulsive
      behavior in quinpirole-treated rats is attenuated by the OCD pharmacotherapeutic
      drug clomipramine. These similarities support the validity of quinpirole-treated
      rats as a psychostimulant-induced animal model of OCD. Considering that the
      induction of compulsive behavior in the rat model involves chronic
      hyperstimulation of dopamine receptors, this raises the possibility that
      dopaminergic mechanisms may play a role in OCD, at least in some subtypes of this
      disorder.

PMID- 15744222
TI  - APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach
      to modeling a CNS disorder.
AB  - Animal models are considered essential in research ensuing elucidation of human
      disease processes and subsequently, testing of potential therapeutic strategies.
      This is especially true for neurodegenerative disorders, in which the first steps
      in pathogenesis are often not accessible in human patients. Alzheimer's disease
      is vastly becoming a major medical and socioeconomic problem in our aging
      society. Valid animal models for this uniquely human condition should exhibit
      histopathological, biochemical, cognitive, and behavioral alterations observed in
      Alzheimer's disease patients. Major progress has been made since the
      understanding of the genetic basis of Alzheimer's disease and the development and
      improvement of transgenic mouse models. All present Alzheimer's disease models
      developed are partial but nevertheless essential in further unraveling the nature
      and spatial and temporal development of the complex molecular pathology
      underlying this condition. One of the more recent transgenic attempts to model
      Alzheimer's disease is the APP23 transgenic mouse. This article describes the
      development and assessment of this human amyloid precursor protein overexpression
      model. We summarize histopathological and biochemical, cognitive and behavioral
      observations made in heterozygous APP23 mice, thereby emphasizing the model's
      contribution to clarification of neurodegenerative disease mechanisms. In
      addition, the first therapeutic interventions in the APP23 model are included.

PMID- 15744223
TI  - Lamotrigine in psychiatry: pharmacology and therapeutics.
AB  - Following the introduction of lamotrigine in 1994 as a treatment for epilepsy in
      the United States, the drug has seen progressively greater application in
      psychiatry, particularly as a treatment for bipolar disorder. This review
      critically evaluates the support for lamotrigine use across a broad range of
      psychiatric disorders as well as discuss its pharmacology, side-effect profile,
      and interactions with other medications.

PMID- 15744224
TI  - Viral vector mediated overexpression of human alpha-synuclein in the
      nigrostriatal dopaminergic neurons: a new model for Parkinson's disease.
AB  - Parkinson's disease is predominantly a dopamine deficiency syndrome, which is
      produced in the brain by the loss of cells located in a small area in the ventral
      midbrain called the substantia nigra. Complete unilateral dopamine lesions, based
      on the administration of toxic substances (ie, 6-hydroxy-dopamine in rats and 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice and primates) have been
      extremely useful in testing strategies of replacement. For example, the
      functional and biochemical impact of the transplanted ventral mesencephalic
      dopaminergic progenitors has been characterized to a large extent, using the
      complete lesion model in rats. Over the last decade, however, studies addressing
      the ability of neurotrophic factors to protect injured dopamine cells prompted
      researchers to make available partial and progressive lesion models to allow a
      window of opportunity to interfere the disease progression. Recent findings
      relating alpha-synuclein with Parkinson's disease pathology have opened new
      possibilities to develop alternative models based on the overexpression of this
      protein using recombinant adeno-associated viral vectors, which is valuable not
      only for helping to better understand its involvement in the disease process, but
      also to more closely resemble the neurodegeneration found in Parkinson's disease.

PMID- 15744226
TI  - Update: influenza activity United States, 2004-05 season.
AB  - Influenza activity has increased steadily in the United States since late
      December and, as of February 19, might not have peaked. Laboratory-confirmed
      influenza infections have been reported from all 50 states. This report
      summarizes influenza activity during October 3, 2004-February 19, 2005.

PMID- 15744227
TI  - Interventions to increase influenza vaccination of health-care workers-
      California and Minnesota.
AB  - Vaccination of health-care workers (HCWs) has been shown to reduce influenza
      infection and absenteeism among HCWs, prevent mortality in their patients, and
      result in financial savings to sponsoring health institutions. However, influenza
      vaccination coverage among HCWs in the United States remains low; in 2003,
      coverage among HCWs was 40.1%. This report describes strategies implemented in
      three clinical settings that increased the proportion of HCWs who received
      influenza vaccination. The results demonstrate the value of making influenza
      vaccination convenient and available at no cost to HCWs.

PMID- 15744228
TI  - Vaccination coverage among callers to a state influenza hotline--Connecticut,
      2004-05 influenza season.
AB  - In response to the influenza vaccine shortage in the United States, the
      Connecticut Department of Public Health (DPH) operated a telephone hotline during
      October 22, 2004-January 15, 2005. The purpose of the hotline was to address
      questions from the public regarding the availability of influenza vaccine, reduce
      the number of telephone inquiries to physicians and local health departments
      (LHDs), and advise callers regarding which groups were most at risk and in need
      of influenza vaccination. Caller information was collected and shared daily with
      LHDs, which were encouraged to follow up with callers as their resources allowed.
      This report summarizes results of a retrospective survey of callers to the DPH
      influenza vaccine hotline during November 2004. The results indicated that
      vaccination coverage varied by age group and that persons receiving follow-up
      calls from LHDs were more likely to receive vaccination. State health departments
      might consider a hotline as a method for educating the public regarding influenza
      vaccination and a follow-up system as a means to improve vaccination coverage,
      especially among those at greatest risk.

PMID- 15744229
TI  - Progress in reducing measles mortality--worldwide, 1999-2003.
AB  - Measles remains an important cause of childhood mortality, especially in
      developing countries. In the joint Strategic Plan for Measles Mortality
      Reduction, 2001-2005, the World Health Organization (WHO) and the United Nations
      Children's Fund (UNICEF) targeted 45 priority countries with high measles burden
      for implementation of a comprehensive strategy for accelerated and sustained
      measles mortality reduction. Components of this strategy include achieving high
      routine vaccination coverage (>/=90%) in every district and ensuring that all
      children receive a second opportunity for measles immunization. In May 2003, the
      World Health Assembly endorsed a resolution urging member countries to reduce
      deaths attributed to measles by half (compared with 1999 estimates) by the end of
      2005. This report updates progress toward this goal and summarizes recent
      recommendations on methods to estimate global measles mortality.

PMID- 15744234
TI  - gammadelta T cells: a new frontier for immunotherapy?
AB  - The use of cytolytic effector cells as therapy for malignant disease has been a
      central focus of basic and clinical research for nearly 2 decades. Since the
      original descriptions of in vitro lymphocyte-mediated cytotoxicity against human
      tumor cells, there have been numerous attempts to exploit such observations for
      therapeutic use, with decidedly mixed results. Most studies have focused on the
      role of either natural killer cells or cytotoxic CD8 + alphabeta T cells as the
      primary mediators of antitumor cytotoxicity, and until recently little attention
      has been paid to the role of gammadelta T cells in this capacity. This is
      partially due to a lack of understanding of the mechanisms of gammadelta T-cell
      immune responses to tumors, as well as the practical problem of obtaining a
      sufficient number of gammadelta T cells for clinical-scale administration. In
      this article, we discuss the biological and clinical rationale for developing
      gammadelta T cell-based immunotherapies for the treatment of a variety of
      malignant conditions. It is our view that infusing supraphysiological numbers of
      tumor-reactive gammadelta T cells-either in the autologous or allogeneic setting
      might be used to restore or augment innate immune responses against malignancies.
      Accordingly, we will also discuss how we and others are working to overcome some
      of the practical limitations that have so far limited the direct clinical
      delivery of highly purified human gammadelta T cells for the treatment of both
      hematologic and solid tumors.

PMID- 15744235
TI  - Amotosalen-treated donor T cells have polyclonal antigen-specific long-term
      function without graft-versus-host disease after allogeneic bone marrow
      transplantation.
AB  - We have previously shown that amotosalen HCl (S-59 psoralen)-treated donor
      splenocytes, which have limited proliferative capacity in vitro, can protect
      major histocompatibility complex-mismatched bone marrow transplant (BMT)
      recipients from lethal murine cytomegalovirus infection without causing graft
      versus-host disease. In this study, we further investigated the effects of
      amotosalen-treated donor T cells on immune reconstitution after allogeneic BMT.
      We were surprised to find that amotosalen-treated donor T cells persisted long
      term in vivo, comprising 6% to 10% on average of the T-cell compartment of
      transplant recipients at 4 months after transplantation. Donor T cells derived
      from amotosalen-treated splenocytes were predominantly polyclonal CD44 hi/int CD8
      + memory T cells and were functionally active, synthesizing interferon gamma in
      response to stimulation with murine cytomegalovirus antigen. Amotosalen-treated
      donor T cells, reisolated from BMT recipients' spleens >/=4 months after
      transplantation, proliferated in vitro, thus indicating repair of amotosalen
      mediated DNA cross-links. Compared with infusion of untreated donor splenocytes,
      amotosalen-treated cells enhanced thymopoiesis by bone marrow-derived stem cells
      in BMT recipients. However, amotosalen treatment abrogated the thymopoietic
      activity of lymphoid progenitor cells among the donor splenocytes. Thus, infusion
      of amotosalen-treated donor T cells produced rapid immune reconstitution after
      major histocompatibility complex-mismatched BMT by transferring long-lived
      polyclonal memory T cells with antiviral activity and also by enhancing bone
      marrow-derived thymopoiesis. This is a novel approach to adoptive immunotherapy
      in allogeneic BMT.

PMID- 15744236
TI  - A phase I trial of autologous cytokine-induced killer cells for the treatment of
      relapsed Hodgkin disease and non-Hodgkin lymphoma.
AB  - We have previously reported on the ex vivo generation of cytotoxic effector
      cells, termed cytokine-induced killer (CIK) cells, that have both in vitro and in
      vivo antitumor activity in murine models. We now report on our efforts for the
      large-scale expansion of CIK cells and also present preliminary results from a
      phase I clinical trial. Nine patients with advanced Hodgkin disease (n = 7) and
      non-Hodgkin lymphoma (n = 2), all of whom had relapsed after an autologous
      transplantation, were treated with escalating doses of CIK cells (3 patients at
      each dose level of 1 x 10(9) , 5 x 10(9) , or 1 x 10(10) cells). The CIK cells
      were produced by culturing unselected cells from steady-state apheresis products
      with interferon gamma, OKT3, and interleukin 2. After 21 days in culture, with
      the addition of fresh media and interleukin 2 every 3 to 4 days, the median
      culture was 97% viable (range, 61%-100%), 98% CD3 + (range, 66%-99%), 76% CD8 +
      (range, 27%-96%), 23% CD4 + (range, 6%-78%), 20% CD3 + CD56 + (range, 8%-58%),
      and <1% CD16 + 56 + (range, 0.2%-7.7%). The CD3 + CD56 + cells have previously
      been shown to exhibit the most cytotoxic activity. The absolute number of CD3 +
      CD56 + cells typically expanded 290-fold (range, 3- to 4000-fold) under these
      culture conditions. In vitro cytotoxic activity was measured against a human B
      cell tumor line (OCI-Ly8). At a 40:1 effector-target cell ratio, CIK cells killed
      32% (range, 2%-69%) of the target cells. A total of 21 infusions were
      administered to 9 patients. The number of CIK cells infused ranged from 1.0 x
      10(9) to 1.0 x 10(10) per treatment. Toxicity was minimal, and there were no
      immediate adverse reactions to the infusions. Two patients had partial responses,
      and 2 patients had stabilization of disease: 1 for more than 18 months.
      Considering that these were heavily pretreated patients with advanced hematologic
      malignancies, we believe that CIK cells expanded in this fashion may have utility
      for the treatment of high-risk patients with evidence of minimal residual disease
      after autologous transplantation.

PMID- 15744237
TI  - Denileukin diftitox for the treatment of steroid-resistant acute graft-versus
      host disease.
AB  - Acute graft-versus-host disease (aGVHD) is partly mediated through activated T
      cells, and these cells are known to express the high-affinity receptor for
      interleukin 2 (IL-2R). Denileukin diftitox is composed of human IL-2 and
      diphtheria toxin that is cytotoxic to activated lymphocytes expressing the high
      affinity IL-2R. We describe the results of a phase II study of denileukin
      diftitox in 22 patients with steroid-resistant aGVHD. Twenty patients were
      treated at dose level 1 (4.5 microg/kg daily on days 1-5 and then weekly on study
      days 8, 15, 22, and 29), and 2 patients were treated at dose level 2 (9.0
      microg/kg delivered on the same schedule). Dose level 2 was associated with grade
      3/4 renal and hepatic toxicity and vascular leak syndrome, and no further
      patients were treated at this level. Dose level 1 was generally well tolerated.
      The response of aGVHD was assessed at study days 36 and 100. Nine patients (41%)
      responded, all with a complete response at study day 36, and 6 patients (27%)
      responded at study day 100 (4 complete responses and 2 partial responses).
      Denileukin diftitox has promising activity in steroid-resistant aGVHD, and
      further study is warranted.

PMID- 15744238
TI  - Onset of thymic recovery and plateau of thymic output are differentially
      regulated after stem cell transplantation in children.
AB  - Thymus-dependent T-cell regeneration is a major pathway for immune reconstitution
      after stem cell transplantation in children. Therefore, we prospectively assessed
      T-cell dynamics and thymic function in 164 pediatric patients between 1 and 124
      months after transplantation by measuring T-cell receptor recombination excision
      circles and spontaneous expression of Ki67 in peripheral T-cell subsets. We
      analyzed the effect of recipient age, conditioning regimen, type of donor and
      graft, stem cell dose, and graft-versus-host disease on the onset and the plateau
      of thymic output. A high rate of spontaneous proliferation in early
      reconstituting naive and memory T cells inversely correlated with total T-cell
      numbers. Accordingly, T-cell receptor recombination excision circle content was
      diminished in early-appearing naive T cells. A multivariate analysis revealed
      that the onset of thymic recovery was inversely correlated only with recipient
      age ( P < .0002), whereas the plateau of thymic output was higher in patients
      receiving increased stem cell numbers ( P < .0022). Donor type, stem cell source,
      and conditioning regimen influenced none of the analyzed parameters. In
      conclusion, lymphopenia-driven proliferation is important for T-cell homeostasis
      in children early after stem cell transplantation, but it might result in
      underestimation of thymic function. Onset and plateau of thymic activity are
      independently regulated by different transplant-related factors.

PMID- 15744239
TI  - The FcgammaRIIa-polymorphic site as a potential target for acute graft-versus
      host disease in allogeneic stem cell transplantation.
AB  - Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem
      cell transplantation for hematologic diseases. Antigen mismatches due to
      polymorphic differences between the patient and donor are central in the
      mechanisms of GVHD. Polymorphisms are known for FcgammaRIIa, and this molecule is
      present on endothelial, dendritic, and Langerhans cells. Donor cells reacting
      against the patient as GVHD can also react against the malignancy of the patient,
      and this is known as the graft-versus-leukemia (GVL) effect. Because the
      FcgammaRIIa molecule is also present on acute myeloid leukemia (AML) cells, an
      FcgammaRIIa mismatch could be a target for both GVHD and GVL. We retrospectively
      studied 73 AML patients and analyzed the differences in GVHD and relapse
      incidence between patients with and without a pro-GVHD/GVL FcgammaRIIa allotype
      mismatch. We observed a difference in FcgammaRIIa receptors with a pro-GVHD/GVL
      mismatch in 18 patient/donor pairs (25%). Univariate and multivariate analyses
      demonstrated the pro-GVHD mismatch to be a significant risk factor for the
      development of acute GVHD. There was no effect on the occurrence of chronic GVHD.
      The relapse incidence was not significantly different for patients with or
      without the pro-GVL mismatch, although there was a trend for fewer relapses in
      standard-risk AML patients with the pro-GVL mismatch. We conclude that the
      polymorphism of the FcgammaRIIa receptor may be a candidate target for acute
      GVHD.

PMID- 15744240
TI  - Protective antibody responses to pneumococcal conjugate vaccine after autologous
      hematopoietic stem cell transplantation.
AB  - Patients undergoing autologous hematopoietic stem cell transplantation (autoHCT)
      are at increased risk for infection with Streptococcus pneumoniae and have
      impaired antibody responses to pneumococcal polysaccharide vaccines. We performed
      this study to examine the ability of autoHCT patients to respond to a heptavalent
      pneumococcal conjugate vaccine (PCV7) given after transplantation and to
      determine whether there was a potential benefit of immunizing these patients
      before stem cell collection. Sixty-one patients scheduled for autoHCT were
      randomized to receive either PCV7 or no vaccine before stem cell collection.
      After stem cell reinfusion, all study patients were immunized with PCV7 at 3, 6,
      and 12 months. Pneumococcal immunoglobulin G antibody concentrations were
      measured at the time of each immunization and 1 month after the 12-month dose.
      Serotype-specific pneumococcal antibody concentrations were significantly higher
      in patients immunized with PCV7 before stem cell collection compared with
      patients not immunized before their stem cells were collected for 6 of 7
      serotypes at 3 months, 6 of 7 serotypes at 6 months, 4 of 7 serotypes at 12
      months, and 3 of 7 serotypes at 13 months. After the 3-dose series of PCV7 after
      autoHCT, >60% of study patients had protective concentrations of antibody to all
      7 vaccine serotypes regardless of immunization before stem cell collection.
      Pneumococcal conjugate vaccine is immunogenic in autoHCT patients and may be an
      effective strategy to prevent invasive disease after transplantation.

PMID- 15744241
TI  - Prediction and prevention of transplant-related mortality from pulmonary causes
      after total body irradiation and allogeneic stem cell transplantation.
AB  - Between July 1997 and August 2004, 146 consecutive patients with hematologic
      malignancies received a T cell-depleted peripheral blood stem cell transplant
      from an HLA-identical sibling by using total body irradiation (TBI) and
      cyclophosphamide conditioning regimens. Eighty-five patients received 13.6 Gy of
      TBI with no lung shielding, and 61 received lung shielding (total lung dose, 6-12
      Gy). Ninety-four patients (65.5%) had standard-risk disease; the remainder had
      more advanced disease or unfavorable diagnoses. Of the 21 transplant-related
      deaths, 14 were from pulmonary causes (10 idiopathic pulmonary syndromes and 4
      from infection) that occurred at a median of 90 days (range, 23-238 days) after
      transplantation. Independent risk factors for pulmonary transplant-related
      mortality (PTRM) were pretransplantation diffusion capacity for carbon monoxide
      (relative risk, 5.7 for diffusion capacity for carbon monoxide <85%), smoking
      (relative risk, 5.0), and CD34 cell dose (relative risk, 9.4 for a CD34 dose of
      <5 x 10(6) cells per kilogram). Patients receiving lung shielding had
      significantly lower PTRM (3.3% versus 14.1%; P = .02) and better overall survival
      (70% +/- 6% versus 52% +/- 5%; P = .04), but lung shielding was not a significant
      independent factor for determining PTRM. These results suggest that pulmonary
      mortality after TBI-based preparative regimens is predictable and that higher
      CD34 cell doses can reduce the risk.

PMID- 15744242
TI  - Effects of race on survival after stem cell transplantation.
AB  - Effects of race or ethnicity on survival after high-dose chemoradiation followed
      by stem cell transplantation (SCT) have not been thoroughly evaluated. We
      analyzed survival according to racial/ethnic categories for 3587 consecutive
      patients who had SCT at a single US institution between July 1992 and December
      2000. Among 1366 patients who received autologous SCT, race or ethnicity was not
      significantly associated with survival. In contrast, among 2221 patients who
      received allogeneic SCT from HLA-matched unrelated or sibling donors, blacks had
      a significantly greater mortality than whites (unadjusted hazard ratio, 1.65; 95%
      confidence interval, 1.21-2.25). Mortality among other racial or ethnic groups
      was not significantly different from that among whites. The greater mortality
      hazard among blacks persisted after controlling for donor type,
      pretransplantation risk category, patient age, donor/patient sex, and
      cytomegalovirus exposure (hazard ratio, 1.71; 95% confidence interval, 1.25
      2.34). SCT from both HLA-matched unrelated and HLA-identical sibling donors was
      associated with more severe acute graft-versus-host disease and higher nonrelapse
      mortality among blacks compared with whites. Furthermore, blacks who received SCT
      for chronic myeloid leukemia had longer diagnosis-to-transplantation intervals
      than whites. A matched-cohort analysis showed that the higher mortality among
      blacks could not be explained by obvious socioeconomic differences. The higher
      incidence of severe graft-versus-host disease among blacks compared with whites,
      both with HLA-identical sibling donors, might be related to yet-unidentified
      "immune-enhancing" genetic polymorphisms. We cannot exclude the possibility that
      the increased mortality risk among blacks after discharge from the transplant
      center might in part be related to unidentified sociocultural differences that
      influence medical care.

PMID- 15744244
TI  - Simultaneous detection of blood volume, oxygenation, and intracellular calcium
      changes during cerebral ischemia and reperfusion in vivo using diffuse
      reflectance and fluorescence.
AB  - We describe an approach to measure changes in intracellular calcium along with
      changes in blood volume and oxygenation directly from the exposed rat cortex in
      vivo during cerebral ischemia and reperfusion. Measurements were made using a
      catheter-based optical system. The endface of a Y-shaped bifurcated fiber optic
      bundle was mounted on the cortical surface. It delivered the light at three
      wavelengths of 548, 555, and 572 nm to the brain through a fast monochromator
      coupled to a xenon lamp, and collected the calcium-dependent fluorescence
      emission from Rhod2 at 589 nm (excited at 548 nm) along with the diffuse
      reflections at the wavelengths of 555 and 572 nm to determine the changes in
      blood volume and hemoglobin oxygenation. The feasibility of this approach was
      experimentally examined by inducing transient cerebral ischemia and reperfusion
      in the rat. The ischemia induced an 8.5%+/-1.7% fluorescence increase compared
      with the preischemic control values. Blood volume and tissue hemoglobin
      oxygenation decreased by 57.4%+/-12.6% and 47.3%+/-12.5%, respectively. All
      signals normalized on reperfusion. The ischemia-induced change in Rhod2-Ca2+
      fluorescence was blocked using a calcium channel blocker, nimodipine, confirming
      that intracellular changes in calcium were responsible for the fluorescence
      changes. Thus, changes in cerebral hemodynamics and intracellular calcium
      concentration changes were measured simultaneously, facilitating future studies
      of the interrelationship between neuronal activation and metabolic and vascular
      processes in normal and diseased brain.

PMID- 15744245
TI  - Mild to moderate hyperthermia does not worsen outcome after severe intracerebral
      hemorrhage in rats.
AB  - Hyperthermia worsens outcome in clinical and experimental studies of ischemic
      stroke. Thus, we tested whether hyperthermia aggravates intracerebral hemorrhage
      (ICH) in rats. A striatal hemorrhage was produced via an infusion of bacterial
      collagenase. In a preliminary experiment, we compared brain and core temperatures
      (via telemetry) during heating (infrared lamp). The brain temperature rise
      exceeded that produced by enforced core hyperthermia, which was used
      subsequently. In these experiments up to three hyperthermia conditions (versus
      normothermia) were tested including: hyperthermia (>38.5 degrees C) over the
      first (HYP-1) or second 24 h period (HYP-2) after ICH and 3 h of 40 degrees C
      hyperthermia starting 12 h after ICH (HYP-3). The HYP-1, HYP-2, and HYP-3
      treatments did not affect functional deficits (e.g., spontaneous forelimb use,
      skilled reaching) or the volume of injury at 30 days. Furthermore, the HYP-1
      treatment did not aggravate injury or deficits at 7 days. Bleeding and
      inflammation, which contribute to pathology, were not significantly altered by
      HYP-1 and HYP-3 treatments. Bleeding was assessed at 1 day, and macrophages and
      neutrophils were counted at 2 and 4 days. Accordingly, hyperthermia, under the
      present conditions, did not worsen outcome after striatal ICH.

PMID- 15744246
TI  - Role of arginine vasopressin V1 and V2 receptors for brain damage after transient
      focal cerebral ischemia.
AB  - Brain edema formation is one of the most important mechanisms responsible for
      brain damage after ischemic stroke. Despite considerable efforts, no specific
      therapy is available yet. Arginine vasopressin (AVP) regulates cerebral water
      homeostasis and has been involved in brain edema formation. In the current study,
      we investigated the role of AVP V1 and V2 receptors on brain damage, brain edema
      formation, and functional outcome after transient focal cerebral ischemia, a
      condition comparable with that of stroke patients undergoing thrombolysis.
      C57/BL6 mice were subjected to 60-min middle cerebral artery occlusion (MCAO)
      followed by 23 h of reperfusion. Five minutes after MCAO, 100 or 500 ng of
      [deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-vasopressin (AVP V1 receptor antagonist) or
      [adamantaneacetyl(1), O-Et-D-Tyr(2), Val(4), Abu(6), Arg(8,9)]-vasopressin (AVP
      V2 receptor antagonist) were injected into the left ventricle. Inhibition of AVP
      V1 receptors reduced infarct volume in a dose-dependent manner by 54% and 70% (to
      29+/-13 and 19+/-10 mm3 versus 63+/-17 mm3 in controls; P<0.001), brain edema
      formation by 67% (to 80.4%+/-1.0% versus 82.7%+/-1.2% in controls; P<0.001),
      blood-brain barrier disruption by 75% (P<0.001), and functional deficits 24 h
      after ischemia, while V2 receptor inhibition had no effect. The current findings
      indicate that AVP V1 but not V2 receptors are involved in the pathophysiology of
      secondary brain damage after focal cerebral ischemia. Although further studies
      are needed to clarify the mechanisms of neuroprotection, AVP V1 receptors seem to
      be promising targets for the treatment of ischemic stroke.

PMID- 15744247
TI  - Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat
      permanent occlusion model.
AB  - Dimethyl sulfoxide (DMSO) has a variety of biological actions that suggest
      efficacy as a neuroprotectant. We (1) tested the neuroprotective potential of
      DMSO at different time windows on infarct size using 2,3,5-triphenyltetrazolium
      staining and (2) investigated the effects of DMSO on ischemia evolution using
      quantitative diffusion and perfusion imaging in a permanent middle cerebral
      artery occlusion (MCAO) model in rats. In experiment 1, DMSO treatment (1.5 g/kg
      intravenously over 3 h) reduced infarct volume 24 h after MCAO by 65% (P<0.00001)
      when initiated 20 h before MCAO, by 44% (P=0.0006) when initiated 1 h after MCAO,
      and by 17% (P=0.11) when started 2 h after MCAO. Significant infarct reduction
      was also observed after a 3-day survival in animals treated 1 h after MCAO
      (P=0.005). In experiment 2, treatment was initiated 1 h after MCAO and maps for
      cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were acquired
      before treatment and then every 30 mins up to 4 h. Cerebral blood flow
      characteristics and CBF-derived lesion volumes did not differ between treated and
      untreated animals, whereas the ADC-derived lesion volume essentially stopped
      progressing during DMSO treatment, resulting in a persistent diffusion/perfusion
      mismatch. This effect was mainly observed in the cortex. Our data suggest that
      DMSO represents an interesting candidate for acute stroke treatment.

PMID- 15744248
TI  - Development of a tracer kinetic plasma input model for (R)-[11C]PK11195 brain
      studies.
AB  - (R)-[(11)C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl]-3
      isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor,
      which, in the brain, is mainly expressed on activated microglia. Using both
      clinical studies and Monte Carlo simulations, the aim of this study was to
      determine which tracer kinetic plasma input model best describes (R)
      [(11)C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were
      performed on 13 subjects while radioactivity in arterial blood was monitored
      online. Discrete blood samples were taken to generate a metabolite corrected
      plasma input function. One-tissue, two-tissue irreversible, and two-tissue
      reversible compartment models, with and without fixing K(1)/k(2) ratio, k(4) or
      blood volume to whole cortex values, were fitted to the data. The effects of
      fixing parameters to incorrect values were investigated by varying them over a
      physiologic range and determining accuracy and reproducibility of binding
      potential and volume of distribution using Monte Carlo simulations. Clinical data
      showed that a two-tissue reversible compartment model was optimal for analyzing
      (R)-[(11)C]PK11195 PET brain studies. Simulations showed that fixing the
      K(1)/k(2) ratio of this model provided the optimal trade-off between accuracy and
      reproducibility. It was concluded that a two-tissue reversible compartment model
      with K(1)/k(2) fixed to whole cortex value is optimal for analyzing (R)
      [(11)C]PK11195 PET brain studies.

PMID- 15744249
TI  - Spatiotemporal evolution of functional hemodynamic changes and their relationship
      to neuronal activity.
AB  - Brain imaging techniques such as functional magnetic resonance imaging (fMRI)
      have provided a wealth of information about brain organization, but their ability
      to investigate fine-scale functional architecture is limited by the spatial
      specificity of the hemodynamic responses upon which they are based. We
      investigated the spatiotemporal evolution of hemodynamic responses in rat
      somatosensory cortex to electrical hindpaw stimulation. We combined the
      advantages of optical intrinsic signal imaging and spectroscopy to produce high
      resolution two-dimensional maps of functional changes in tissue oxygenation and
      blood volume. Cerebral blood flow changes were measured with laser-Doppler
      flowmetry, and simultaneously recorded field potentials allowed comparison
      between hemodynamic changes and underlying neuronal activity. For the first 2 to
      3 secs of activation, hemodynamic responses overlapped in a central parenchymal
      focus. Over the next several seconds, cerebral blood volume changes propagated
      retrograde into feeding arterioles, and oxygenation changes anterograde into
      draining veins. By 5 to 6 secs, responses localized primarily in vascular
      structures distant from the central focus. The peak spatial extent of the
      hemodynamic response increased linearly with synaptic activity. This spatial
      spread might be because of lateral subthreshold activation or passive vascular
      overspill. These results imply early microvascular changes in volume and
      oxygenation localize to activated neural columns, and that spatial specificity
      will be optimal within a 2- to 3-sec window after neuronal activation.

PMID- 15744250
TI  - Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from
      infants with inflicted brain injury from child abuse.
AB  - Previous studies suggest that delayed neuronal death occurs in patients with
      inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether
      the mode of this delayed neuronal death represents apoptosis or necrosis, a
      distinction that carries therapeutic ramifications. Cytochrome c, an electron
      transport chain component, can be released from mitochondria under conditions of
      cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis.
      To resolve this issue, cytochrome c concentration was determined in 167
      ventricular cerebrospinal fluid (CSF) samples from 67 infants and children with
      TBI (including 15 patients diagnosed with child abuse) by ELISA. Controls
      included lumbar CSF from 19 infants and children without trauma or meningitis. A
      multivariate model adjusted for multiple within-subject observations was used to
      identify clinical variables associated with CSF cytochrome c. Other apoptosis
      related proteins were also examined in a subset of TBI patients. Increased CSF
      cytochrome c was independently associated with inflicted TBI (P=0.0001) and
      female gender (P=0.04), but not age, Glasgow coma scale score, or survival. Other
      apoptosis-related proteins including Fas and caspase-1 were increased in CSF
      after TBI, but did not independently discriminate between accidental and
      inflicted TBI. These data suggest that apoptosis, as detected by the presence of
      cytochrome c in CSF, is uniquely prominent among the subset of TBI patients
      diagnosed with child abuse. The degree of apoptosis after TBI also appears to be
      gender-dependent. Development of strategies targeting apoptosis after TBI,
      particularly in victims of child abuse and in girls, appears justified.

PMID- 15744251
TI  - Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain
      injury.
AB  - Apoptosis is implicated in neonatal hypoxic/ischemic (H/I) brain injury among
      various forms of cell death. Here we investigate whether overexpression of heat
      shock protein (Hsp) 70, an antiapoptotic protein, protects the neonatal brain
      from H/I injury and the pathways involved in the protection. Postnatal day 7 (P7)
      transgenic mice overexpressing rat Hsp70 (Tg) and their wild-type littermates
      (Wt) underwent unilateral common carotid artery ligation followed by 30 mins
      exposure to 8% O(2). Significant neuroprotection was observed in Tg versus Wt
      mice on both P12 and P21, correlating with a high level of constitutive but not
      inducible Hsp70 in the Tg. More prominent injury was observed in Wt and Tg mice
      on P21, suggesting its continuous evolution after P12. Western blot analysis
      showed that translocation of cytochrome c, but not the second mitochondria
      derived activator of caspase (Smac)/DIABLO and apoptosis-inducing factor (AIF),
      from mitochondria into cytosol was significantly reduced in Tg 24 h after H/I
      compared with Wt mice. Coimmunoprecipitation detected more Hsp70 bound to AIF in
      Tg than Wt mice 24 h after H/I, inversely correlating with the amount of nuclear,
      but not cytosolic, AIF translocation. Our results suggest that interaction
      between Hsp70 and AIF might have reduced downstream events leading to cell death,
      including the reduction of nuclear AIF translocation in the neonatal brains of
      Hsp70 Tg mice after H/I.

PMID- 15744252
TI  - Preferred stereoselective transport of the D-isomer of cis-4-[18F]fluoro-proline
      at the blood-brain barrier.
AB  - Generally, L-amino acids are preferably transported into mammalian cells compared
      with their D-isomers, and only L-amino acids are incorporated into proteins.
      Former studies, however, indicated that D-[H]proline is accumulated in the brain
      of mice after injection, while L-[3H]proline is not. We investigated the
      differential cerebral uptake of the D- and L-isomers of the PET tracer cis-4
      [18F]fluoroproline (D-/L-cis-FPro) and of D-/L-[3H]proline (D-/L-Pro) in rats by
      dual tracer autoradiography and the uptake of D-cis-FPro in two human subjects by
      PET. The standardized uptake value (SUV) of D-cis-FPro in the cerebral cortex of
      rats 2 h p.i. was 3.05+/-1.18 (n=9) versus 0.06+/-0.01 (n=4) for L-cis-FPro
      (P<0.001) and 1.29+/-0.27 (n=4) for D-Pro versus 0.30+/-0.14 (n=9) for L-Pro
      (P<0.001). Analysis of the rat brain tissue after injection of D-cis-FPro (n=3)
      revealed no radioactivity in the proteins but a relevant part in the form of L
      trans-FPro. The PET studies yielded a four- to five-fold higher SUV and influx
      rate constant in the human cortex for D-cis-FPro than for L-cis-FPro. We conclude
      that D-cis-FPro and D-Pro are preferably transported at the blood-brain barrier
      compared with their L-isomers and isomerized to the L-form within the brain.
      Thus, D-Pro in the plasma might be a source of intracerebral L-proline, which has
      been shown to act as a modulator of excitatory neurotransmission.

PMID- 15744254
TI  - In pursuit of balance.

PMID- 15744253
TI  - Cerebral fractional oxygen extraction is inversely correlated with oxygen
      delivery in the sick, newborn, preterm infant.
AB  - Cerebral blood flow (CBF) is known to be low in newborn infants, but this has not
      been shown to be damaging. The purpose of this study was to investigate the
      relationships between cerebral haemoglobin flow, blood flow, oxygen delivery,
      oxygen consumption, venous saturation, and fractional oxygen extraction (OEF) in
      newborn, preterm infants. Measurements were made by near-infrared spectroscopy in
      13 very preterm, extremely low birth weight infants (median gestation 25 weeks)
      during the first 3 days after birth. There was a negative correlation between
      cerebral oxygen delivery and OEF (n=13, r=-0.5, P=0.03), which implies that when
      there is a reduction in cerebral oxygen delivery in sick preterm infants,
      increased cerebral oxygen extraction may be responsible for maintaining oxygen
      availability to the brain. During the first 3 days after birth CBF (n=13, r=0.7,
      P=0.01), oxygen delivery (n=13, r=0.5, P=0.03), and oxygen consumption (n=13,
      r=0.7, P=0.004) all increased. This increase in oxygen consumption indicates
      increased cerebral metabolic activity after birth, which is likely to be a normal
      adaptation to extrauterine life. The increases in blood flow and oxygen delivery
      may also be normal adaptations that facilitate this increase in metabolic
      activity. There was a decrease (P=0.04) in mean (+/-s.d.) cerebral OEF between
      day 1 (0.37+/-0.10) and day 2 (0.29+/-0.09), with no change between day 2 and day
      3. Taking into account the negative correlation between OEF and oxygen delivery,
      this decrease in OEF may be because of increased oxygen delivery during this
      time.

PMID- 15744255
TI  - Why Harvard needs Summers.

PMID- 15744256
TI  - NIH workers see red over revised rules for conflicts of interest.

PMID- 15744257
TI  - Physicists miss out on critical points as magazines vanish.

PMID- 15744258
TI  - France lays plans for premier cancer centre in Toulouse.

PMID- 15744259
TI  - Fossil finders in tug of war over analysis of hobbit bones.

PMID- 15744260
TI  - Agency to bring fast-breeder reactor out of mothballs.

PMID- 15744261
TI  - Japanese call for more bite in animal rules.

PMID- 15744262
TI  - Pasteur researchers win fight to stay in city centre.

PMID- 15744263
TI  - Protest letter accuses health agency of biodefence bias.

PMID- 15744265
TI  - US science policy: upstart states.

PMID- 15744266
TI  - Antiquities fraud: reality check.

PMID- 15744267
TI  - India must cooperate on tsunami warning system.

PMID- 15744268
TI  - Solid evidence for bubble fusion?

PMID- 15744269
TI  - Coping with unsuspected findings in volunteers.

PMID- 15744270
TI  - How volunteering for an MRI scan changed my life.

PMID- 15744271
TI  - Making sure corrections don't vanish online.

PMID- 15744273
TI  - Ethics and ethnoflora.

PMID- 15744272
TI  - Biologists do not pose a threat to deep-sea vents.

PMID- 15744274
TI  - Watching over the world's oceans.

PMID- 15744280
TI  - Coupling and cross-presentation.

PMID- 15744281
TI  - Astronomy: blasts from the radio heavens.

PMID- 15744282
TI  - Evolutionary biology: the hydrogenosome's murky past.

PMID- 15744283
TI  - Atmospheric chemistry: the decay of organic aerosols.

PMID- 15744284
TI  - Biodiversity: an index of intactness.

PMID- 15744286
TI  - Sonoluminescence: cavitation hots up.

PMID- 15744287
TI  - Cell cycle: cyclin guides the way.

PMID- 15744290
TI  - Physiology: postprandial cardiac hypertrophy in pythons.
AB  - Oxygen consumption by carnivorous reptiles increases enormously after they have
      eaten a large meal in order to meet metabolic demands, and this places an extra
      load on the cardiovascular system. Here we show that there is an extraordinarily
      rapid 40% increase in ventricular muscle mass in Burmese pythons (Python molurus)
      a mere 48 hours after feeding, which results from increased gene expression of
      muscle-contractile proteins. As this fully reversible hypertrophy occurs
      naturally, it could provide a useful model for investigating the mechanisms that
      lead to cardiac growth in other animals.

PMID- 15744291
TI  - Synaesthesia: when coloured sounds taste sweet.
AB  - Synaesthesia is the involuntary physical experience of a cross-modal linkage--for
      example, hearing a tone (the inducing stimulus) evokes an additional sensation of
      seeing a colour (concurrent perception). Of the different types of synaesthesia,
      most have colour as the concurrent perception, with concurrent perceptions of
      smell or taste being rare. Here we describe the case of a musician who
      experiences different tastes in response to hearing different musical tone
      intervals, and who makes use of her synaesthetic sensations in the complex task
      of tone-interval identification. To our knowledge, this combination of inducing
      stimulus and concurrent perception has not been described before.

PMID- 15744292
TI  - Quantum computing with realistically noisy devices.
AB  - In theory, quantum computers offer a means of solving problems that would be
      intractable on conventional computers. Assuming that a quantum computer could be
      constructed, it would in practice be required to function with noisy devices
      called 'gates'. These gates cause decoherence of the fragile quantum states that
      are central to the computer's operation. The goal of so-called 'fault-tolerant
      quantum computing' is therefore to compute accurately even when the error
      probability per gate (EPG) is high. Here we report a simple architecture for
      fault-tolerant quantum computing, providing evidence that accurate quantum
      computing is possible for EPGs as high as three per cent. Such EPGs have been
      experimentally demonstrated, but to avoid excessive resource overheads required
      by the necessary architecture, lower EPGs are needed. Assuming the availability
      of quantum resources comparable to the digital resources available in today's
      computers, we show that non-trivial quantum computations at EPGs of as high as
      one per cent could be implemented.

PMID- 15744293
TI  - A biodiversity intactness index.
AB  - The nations of the world have set themselves a target of reducing the rate of
      biodiversity loss by 2010. Here, we propose a biodiversity intactness index (BII)
      for assessing progress towards this target that is simple and practical--but
      sensitive to important factors that influence biodiversity status--and which
      satisfies the criteria for policy relevance set by the Convention on Biological
      Diversity. Application of the BII is demonstrated on a large region (4 x 10(6)
      km2) of southern Africa. The BII score in the year 2000 is about 84%: in other
      words, averaged across all plant and vertebrate species in the region,
      populations have declined to 84% of their presumed pre-modern levels. The
      taxonomic group with the greatest loss is mammals, at 71% of pre-modern levels,
      and the ecosystem type with the greatest loss is grassland, with 74% of its
      former populations remaining. During the 1990s, a population decline of 0.8% is
      estimated to have occurred.

PMID- 15744294
TI  - A powerful bursting radio source towards the Galactic Centre.
AB  - Transient astronomical sources are typically powered by compact objects and
      usually signify highly explosive or dynamic events. Although high-time-resolution
      observations are often possible in radio astronomy, they are usually limited to
      quite narrow fields of view. The dynamic radio sky is therefore poorly sampled,
      in contrast to the situation in the X-ray and gamma-ray bands in which wide-field
      instruments routinely detect transient sources. Here we report a transient radio
      source, GCRT J1745-3009, which was detected during a moderately wide-field
      monitoring programme of the Galactic Centre region at 0.33 GHz. The
      characteristics of its bursts are unlike those known for any other class of radio
      transient. If located in or near the Galactic Centre, its brightness temperature
      (approximately 10(16) K) and the implied energy density within GCRT J1745-3009
      vastly exceed those observed in most other classes of radio astronomical sources,
      and are consistent with coherent emission processes that are rarely observed. We
      conclude that it represents a hitherto unknown class of transient radio sources,
      the first of possibly many new classes that may be discovered by emerging wide
      field radio telescopes.

PMID- 15744295
TI  - Plasma formation and temperature measurement during single-bubble cavitation.
AB  - Single-bubble sonoluminescence (SBSL) results from the extreme temperatures and
      pressures achieved during bubble compression; calculations have predicted the
      existence of a hot, optically opaque plasma core with consequent bremsstrahlung
      radiation. Recent controversial reports claim the observation of neutrons from
      deuterium-deuterium fusion during acoustic cavitation. However, there has been
      previously no strong experimental evidence for the existence of a plasma during
      single- or multi-bubble sonoluminescence. SBSL typically produces featureless
      emission spectra that reveal little about the intra-cavity physical conditions or
      chemical processes. Here we report observations of atomic (Ar) emission and
      extensive molecular (SO) and ionic (O2+) progressions in SBSL spectra from
      concentrated aqueous H2SO4 solutions. Both the Ar and SO emission permit
      spectroscopic temperature determinations, as accomplished for multi-bubble
      sonoluminescence with other emitters. The emissive excited states observed from
      both Ar and O2+ are inconsistent with any thermal process. The Ar excited states
      involved are extremely high in energy (>13 eV) and cannot be thermally populated
      at the measured Ar emission temperatures (4,000-15,000 K); the ionization energy
      of O2 is more than twice its bond dissociation energy, so O2+ likewise cannot be
      thermally produced. We therefore conclude that these emitting species must
      originate from collisions with high-energy electrons, ions or particles from a
      hot plasma core.

PMID- 15744296
TI  - Self-directed self-assembly of nanoparticle/copolymer mixtures.
AB  - The organization of inorganic nanostructures within self-assembled organic or
      biological templates is receiving the attention of scientists interested in
      developing functional hybrid materials. Previous efforts have concentrated on
      using such scaffolds to spatially arrange nanoscopic elements as a strategy for
      tailoring the electrical, magnetic or photonic properties of the material. Recent
      theoretical arguments have suggested that synergistic interactions between self
      organizing particles and a self-assembling matrix material can lead to
      hierarchically ordered structures. Here we show that mixtures of diblock
      copolymers and either cadmium selenide- or ferritin-based nanoparticles exhibit
      cooperative, coupled self-assembly on the nanoscale. In thin films, the
      copolymers assemble into cylindrical domains, which dictate the spatial
      distribution of the nanoparticles; segregation of the particles to the interfaces
      mediates interfacial interactions and orients the copolymer domains normal to the
      surface, even when one of the blocks is strongly attracted to the substrate.
      Organization of both the polymeric and particulate entities is thus achieved
      without the use of external fields, opening a simple and general route for
      fabrication of nanostructured materials with hierarchical order.

PMID- 15744297
TI  - Mesozoic Alpine facies deposition as a result of past latitudinal plate motion.
AB  - The fragmentation of Pangaea as a consequence of the opening of the Atlantic
      Ocean is documented in the Alpine-Mediterranean region by the onset of widespread
      pelagic sedimentation. Shallow-water sediments were replaced by mainly pelagic
      limestones in the Early Jurassic period, radiolarian cherts in the Middle-Late
      Jurassic period, and again pelagic limestones in the Late Jurassic-Cretaceous
      period. During initial extension, basin subsidence below the carbonate
      compensation depth (CCD) is thought to have triggered the transition from Early
      Jurassic limestones to Middle-Late Jurassic radiolarites. It has been proposed
      that the transition from radiolarites to limestones in the Late Jurassic period
      was due to an increase in calcareous nannoplankton abundance when the CCD was
      depressed below the ocean floor. But in modern oceans, sediments below the CCD
      are not necessarily radiolaritic. Here we present palaeomagnetic samples from the
      Jurassic-Cretaceous pelagic succession exposed in the Lombardian basin, Italy. On
      the basis of an analysis of our palaeolatitudinal data in a broader
      palaeogeographic context, we propose an alternative explanation for the above
      facies tripartition. We suggest that the Lombardian basin drifted initially
      towards, and subsequently away from, a near-equatorial upwelling zone of high
      biosiliceous productivity. Our tectonic model for the genesis of radiolarites
      adds an essential horizontal plate motion component to explanations involving
      only vertical variations of CCD relative to the ocean floor. It may explain the
      deposition of radiolarites throughout the Mediterranean and Middle Eastern region
      during the Jurassic period.

PMID- 15744298
TI  - Insolation-driven changes in atmospheric circulation over the past 116,000 years
      in subtropical Brazil.
AB  - During the last glacial period, large millennial-scale temperature oscillations-
      the 'Dansgaard/Oeschger' cycles--were the primary climate signal in Northern
      Hemisphere climate archives from the high latitudes to the tropics. But whether
      the influence of these abrupt climate changes extended to the tropical and
      subtropical Southern Hemisphere, where changes in insolation are thought to be
      the main direct forcing of climate, has remained unclear. Here we present a high
      resolution oxygen isotope record of a U/Th-dated stalagmite from subtropical
      southern Brazil, covering the past 116,200 years. The oxygen isotope signature
      varies with shifts in the source region and amount of rainfall in the area, and
      hence records changes in atmospheric circulation and convective intensity over
      South America. We find that these variations in rainfall source and amount are
      primarily driven by summer solar radiation, which is controlled by the Earth's
      precessional cycle. The Dansgaard/Oeschger cycles can be detected in our record
      and therefore we confirm that they also affect the tropical hydrological cycle,
      but that in southern subtropical Brazil, millennial-scale climate changes are not
      as dominant as they are in the Northern Hemisphere.

PMID- 15744299
TI  - Water-rich basalts at mid-ocean-ridge cold spots.
AB  - Although water is only present in trace amounts in the suboceanic upper mantle,
      it is thought to play a significant role in affecting mantle viscosity, melting
      and the generation of crust at mid-ocean ridges. The concentration of water in
      oceanic basalts has been observed to stay below 0.2 wt%, except for water-rich
      basalts sampled near hotspots and generated by 'wet' mantle plumes. Here,
      however, we report unusually high water content in basaltic glasses from a cold
      region of the mid-ocean-ridge system in the equatorial Atlantic Ocean. These
      basalts are sodium-rich, having been generated by low degrees of melting of the
      mantle, and contain unusually high ratios of light versus heavy rare-earth
      elements, implying the presence of garnet in the melting region. We infer that
      water-rich basalts from such regions of thermal minima derive from low degrees of
      'wet' melting greater than 60 km deep in the mantle, with minor dilution by melts
      produced by shallower 'dry' melting--a view supported by numerical modelling. We
      therefore conclude that oceanic basalts are water-rich not only near hotspots,
      but also at 'cold spots'.

PMID- 15744300
TI  - Kin selection and cooperative courtship in wild turkeys.
AB  - In the few species of birds in which males form display partnerships to attract
      females, one male secures most or all of the copulations. This leads to the
      question of why subordinate males help in the absence of observable reproductive
      benefits. Hamilton's concept of kin selection, whereby individuals can benefit
      indirectly by helping a relative, was a crucial breakthrough for understanding
      apparently altruistic systems. However in the only direct test of kin selection
      in coordinated display partnerships, partners were unrelated, discounting kin
      selection as an explanation for the evolution of cooperation. Here I show, using
      genetic measures of relatedness and reproductive success, that kin selection can
      explain the evolution of cooperative courtship in wild turkeys. Subordinate
      (helper) males do not themselves reproduce, but their indirect fitness as
      calculated by Hamilton's rule more than offsets the cost of helping. This result
      confirms a textbook example of kin selection that until now has been
      controversial and also extends recent findings of male relatedness on avian leks
      by quantifying the kin-selected benefits gained by non-reproducing males.

PMID- 15744301
TI  - Disruptive coloration and background pattern matching.
AB  - Effective camouflage renders a target indistinguishable from irrelevant
      background objects. Two interrelated but logically distinct mechanisms for this
      are background pattern matching (crypsis) and disruptive coloration: in the
      former, the animal's colours are a random sample of the background; in the
      latter, bold contrasting colours on the animal's periphery break up its outline.
      The latter has long been proposed as an explanation for some apparently
      conspicuous coloration in animals, and is standard textbook material.
      Surprisingly, only one quantitative test of the theory exists, and one
      experimental test of its effectiveness against non-human predators. Here we test
      two key predictions: that patterns on the body's outline should be particularly
      effective in promoting concealment and that highly contrasting colours should
      enhance this disruptive effect. Artificial moth-like targets were exposed to bird
      predation in the field, with the experimental colour patterns on the 'wings' and
      a dead mealworm as the edible 'body'. Survival analysis supported the
      predictions, indicating that disruptive coloration is an effective means of
      camouflage, above and beyond background pattern matching.

PMID- 15744303
TI  - Image segmentation and lightness perception.
AB  - The perception of surface albedo (lightness) is one of the most basic aspects of
      visual awareness. It is well known that the apparent lightness of a target
      depends on the context in which it is embedded, but there is extensive debate
      about the computations and representations underlying perceived lightness. One
      view asserts that the visual system explicitly separates surface reflectance from
      the prevailing illumination and atmospheric conditions in which it is embedded,
      generating layered image representations. Some recent theory has challenged this
      view and asserted that the human visual system derives surface lightness without
      explicitly segmenting images into multiple layers. Here we present new lightness
      illusions--the largest reported to date--that unequivocally demonstrate the
      effect that layered image representations can have in lightness perception. We
      show that the computations that underlie the decomposition of luminance into
      multiple layers under conditions of transparency can induce dramatic lightness
      illusions, causing identical texture patches to appear either black or white.
      These results indicate that mechanisms involved in decomposing images into
      layered representations can play a decisive role in the perception of surface
      lightness.

PMID- 15744302
TI  - An anaerobic mitochondrion that produces hydrogen.
AB  - Hydrogenosomes are organelles that produce ATP and hydrogen, and are found in
      various unrelated eukaryotes, such as anaerobic flagellates, chytridiomycete
      fungi and ciliates. Although all of these organelles generate hydrogen, the
      hydrogenosomes from these organisms are structurally and metabolically quite
      different, just like mitochondria where large differences also exist. These
      differences have led to a continuing debate about the evolutionary origin of
      hydrogenosomes. Here we show that the hydrogenosomes of the anaerobic ciliate
      Nyctotherus ovalis, which thrives in the hindgut of cockroaches, have retained a
      rudimentary genome encoding components of a mitochondrial electron transport
      chain. Phylogenetic analyses reveal that those proteins cluster with their
      homologues from aerobic ciliates. In addition, several nucleus-encoded components
      of the mitochondrial proteome, such as pyruvate dehydrogenase and complex II,
      were identified. The N. ovalis hydrogenosome is sensitive to inhibitors of
      mitochondrial complex I and produces succinate as a major metabolic end product-
      biochemical traits typical of anaerobic mitochondria. The production of hydrogen,
      together with the presence of a genome encoding respiratory chain components, and
      biochemical features characteristic of anaerobic mitochondria, identify the N.
      ovalis organelle as a missing link between mitochondria and hydrogenosomes.

PMID- 15744304
TI  - Cross-presentation by intercellular peptide transfer through gap junctions.
AB  - Major histocompatibility complex (MHC) class I molecules present peptides that
      are derived from endogenous proteins. These antigens can also be transferred to
      professional antigen-presenting cells in a process called cross-presentation,
      which precedes initiation of a proper T-cell response; but exactly how they do
      this is unclear. We tested whether peptides can be transferred directly from the
      cytoplasm of one cell into the cytoplasm of its neighbour through gap junctions.
      Here we show that peptides with a relative molecular mass of up to approximately
      1,800 diffuse intercellularly through gap junctions unless a three-dimensional
      structure is imposed. This intercellular peptide transfer causes cytotoxic T-cell
      recognition of adjacent, innocent bystander cells as well as activated monocytes.
      Gap-junction-mediated peptide transfer is restricted to a few coupling cells
      owing to the high cytosolic peptidase activity. We present a mechanism of antigen
      acquisition for cross-presentation that couples the antigen presentation system
      of two adjacent cells and is lost in most tumours: gap-junction-mediated
      intercellular peptide coupling for presentation by bystander MHC class I
      molecules and transfer to professional antigen presenting cells for cross
      priming.

PMID- 15744305
TI  - CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation
      induced cell death.
AB  - The 'help' provided by CD4+ T lymphocytes during the priming of CD8+ T
      lymphocytes confers a key feature of immune memory: the capacity for autonomous
      secondary expansion following re-encounter with antigen. Once primed in the
      presence of CD4+ T cells, 'helped' CD8+ T cells acquire the ability to undergo a
      second round of clonal expansion upon restimulation in the absence of T-cell
      help. 'Helpless' CD8+ T cells that are primed in the absence of CD4+ T cells, in
      contrast, can mediate effector functions such as cytotoxicity and cytokine
      secretion upon restimulation, but do not undergo a second round of clonal
      expansion. These disparate responses have features of being 'programmed', that
      is, guided by signals that are transmitted to naive CD8+ T cells during priming,
      which encode specific fates for their clonal progeny. Here we explore the
      instructional programme that governs the secondary response of CD8+ T cells and
      find that helpless cells undergo death by activation-induced cell death upon
      secondary stimulation. This death is mediated by tumour-necrosis factor (TNF)
      related apoptosis-inducing ligand (TRAIL). Regulation of Trail expression can
      therefore account for the role of CD4+ T cells in the generation of CD8+ T cell
      memory and represents a novel mechanism for controlling adaptive immune
      responses.

PMID- 15744306
TI  - Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal
      in C. elegans.
AB  - The removal of apoptotic cells is essential for the physiological well being of
      the organism. In Caenorhabditis elegans, two conserved, partially redundant
      genetic pathways regulate this process. In the first pathway, the proteins CED-2,
      CED-5 and CED-12 (mammalian homologues CrkII, Dock180 and ELMO, respectively)
      function to activate CED-10 (Rac1). In the second group, the candidate receptor
      CED-1 (CD91/LRP/SREC) probably recognizes an unknown ligand on the apoptotic cell
      and signals via its cytoplasmic tail to the adaptor protein CED-6 (hCED-6/GULP),
      whereas CED-7 (ABCA1) is thought to play a role in membrane dynamics. Molecular
      understanding of how the second pathway promotes engulfment of the apoptotic cell
      is lacking. Here, we show that CED-1, CED-6 and CED-7 are required for actin
      reorganization around the apoptotic cell corpse, and that CED-1 and CED-6
      colocalize with each other and with actin around the dead cell. Furthermore, we
      find that the CED-10(Rac) GTPase acts genetically downstream of these proteins to
      mediate corpse removal, functionally linking the two engulfment pathways and
      identifying the CED-1, -6 and -7 signalling module as upstream regulators of Rac
      activation.

PMID- 15744307
TI  - Phospholipase Cgamma1 controls surface expression of TRPC3 through an
      intermolecular PH domain.
AB  - Many ion channels are regulated by lipids, but prominent motifs for lipid binding
      have not been identified in most ion channels. Recently, we reported that
      phospholipase Cgamma1 (PLC-gamma1) binds to and regulates TRPC3 channels,
      components of agonist-induced Ca2+ entry into cells. This interaction requires a
      domain in PLC-gamma1 that includes a partial pleckstrin homology (PH) domain-a
      consensus lipid-binding and protein-binding sequence. We have developed a gestalt
      algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report
      that the partial PH domain of PLC-gamma1 interacts with a complementary partial
      PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of
      TRPC3. Our findings imply a far greater abundance of PH domains than previously
      appreciated, and suggest that intermolecular PH-like domains represent a
      widespread signalling mode.

PMID- 15744308
TI  - Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates.
AB  - Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose
      periodic activation is driven by cyclins. Different cyclins promote distinct cell
      cycle events, but the molecular basis for these differences remains unclear. Here
      we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5
      and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28)
      substrates. About 24% of these proteins were phosphorylated more efficiently by
      Clb5-Cdk1 than Clb2-Cdk1. The Clb5-specific targets include several proteins
      (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events. Clb5
      specificity depended on an interaction between a hydrophobic patch in Clb5 and a
      short sequence in the substrate (the RXL or Cy motif). Phosphorylation of Clb5
      specific targets during S phase was reduced by replacing Clb5 with Clb2 or by
      mutating the substrate RXL motif, confirming the importance of Clb5 specificity
      in vivo. Although we did not identify any highly Clb2-specific substrates, we
      found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1,
      enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets.
      Thus, Clb5 and Clb2 use distinct mechanisms to enhance the phosphorylation of S
      phase and M-phase substrates.

PMID- 15744309
TI  - Defective DNA single-strand break repair in spinocerebellar ataxia with axonal
      neuropathy-1.
AB  - Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is a neurodegenerative
      disease that results from mutation of tyrosyl phosphodiesterase 1 (TDP1). In
      lower eukaryotes, Tdp1 removes topoisomerase 1 (top1) peptide from DNA termini
      during the repair of double-strand breaks created by collision of replication
      forks with top1 cleavage complexes in proliferating cells. Although TDP1 most
      probably fulfils a similar function in human cells, this role is unlikely to
      account for the clinical phenotype of SCAN1, which is associated with progressive
      degeneration of post-mitotic neurons. In addition, this role is redundant in
      lower eukaryotes, and Tdp1 mutations alone confer little phenotype. Moreover,
      defects in processing or preventing double-strand breaks during DNA replication
      are most probably associated with increased genetic instability and cancer,
      phenotypes not observed in SCAN1 (ref. 8). Here we show that in human cells TDP1
      is required for repair of chromosomal single-strand breaks arising independently
      of DNA replication from abortive top1 activity or oxidative stress. We report
      that TDP1 is sequestered into multi-protein single-strand break repair (SSBR)
      complexes by direct interaction with DNA ligase IIIalpha and that these complexes
      are catalytically inactive in SCAN1 cells. These data identify a defect in SSBR
      in a neurodegenerative disease, and implicate this process in the maintenance of
      genetic integrity in post-mitotic neurons.

PMID- 15744310
TI  - Nutrient control of glucose homeostasis through a complex of PGC-1alpha and
      SIRT1.
AB  - Homeostatic mechanisms in mammals respond to hormones and nutrients to maintain
      blood glucose levels within a narrow range. Caloric restriction causes many
      changes in glucose metabolism and extends lifespan; however, how this metabolism
      is connected to the ageing process is largely unknown. We show here that the Sir2
      homologue, SIRT1--which modulates ageing in several species--controls the
      gluconeogenic/glycolytic pathways in liver in response to fasting signals through
      the transcriptional coactivator PGC-1alpha. A nutrient signalling response that
      is mediated by pyruvate induces SIRT1 protein in liver during fasting. We find
      that once SIRT1 is induced, it interacts with and deacetylates PGC-1alpha at
      specific lysine residues in an NAD(+)-dependent manner. SIRT1 induces
      gluconeogenic genes and hepatic glucose output through PGC-1alpha, but does not
      regulate the effects of PGC-1alpha on mitochondrial genes. In addition, SIRT1
      modulates the effects of PGC-1alpha repression of glycolytic genes in response to
      fasting and pyruvate. Thus, we have identified a molecular mechanism whereby
      SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These
      findings have strong implications for the basic pathways of energy homeostasis,
      diabetes and lifespan.

PMID- 15744314
TI  - Nuts and bolts. Networking for introverts.

PMID- 15744317
TI  - Painful lessons.

PMID- 15744318
TI  - How RNA closes a Diel.

PMID- 15744319
TI  - Some assembly required.

PMID- 15744320
TI  - Rings around kinetochore microtubules in yeast.

PMID- 15744321
TI  - Mediating repair.

PMID- 15744322
TI  - RecA kicks Pol V into gear.

PMID- 15744326
TI  - Multisite protein modification and intramolecular signaling.
AB  - Post-translational modification is a major mechanism by which protein function is
      regulated in eukaryotes. Instead of single-site action, many proteins such as
      histones, p53, RNA polymerase II, tubulin, Cdc25C and tyrosine kinases are
      modified at multiple sites by modifications like phosphorylation, acetylation,
      methylation, ubiquitination, sumoylation and citrullination. Multisite
      modification on a protein constitutes a complex regulatory program that resembles
      a dynamic 'molecular barcode' and transduces molecular information to and from
      signaling pathways. This program imparts effects through 'loss-of-function' and
      'gain-of-function' mechanisms. Among the latter, covalent modifications
      specifically recruit a diverse array of modules, including the SH2 domain, 14-3
      3, WW domain, Polo box, BRCT repeat, bromodomain, chromodomain, Tudor domain and
      motifs binding to ubiquitin and other protein modifiers. Such recruitments are
      often modulated by modifications occurred at neighboring and distant sites.
      Multisite modification thus coordinates intermolecular and intramolecular
      signaling for the qualitative and quantitative control of protein function in
      vivo.

PMID- 15744328
TI  - Malnutrition and associated factors among aged residents in all nursing homes in
      Helsinki.
AB  - OBJECTIVE: To acquire information about nutritional problems and factors
      associated with them in all nursing homes in Helsinki, Finland. DESIGN:
      Descriptive, cross-sectional study. The residents were assessed by the Mini
      Nutritional Assessment test (MNA) and information was gathered about residents'
      backgrounds, functional status, diseases and about daily routines in institutions
      providing nutritional care. SETTING: All nursing homes in Helsinki community, the
      capital of Finland. SUBJECTS: Of 2424 eligible subjects, 2114 (87%) aged
      residents, mean age 82 y, were examined. RESULTS: One-third (29%) of the studied
      residents suffered from malnutrition (MNA < 17), and 60% were at risk (MNA 17
      23.5). Malnutrition was associated with the female gender, a longer stay in the
      nursing home, functional impairment, dementia, stroke, constipation and
      difficulties in swallowing. In addition, eating less than half of the offered
      food portion, not eating snacks and resident's weight control at long intervals
      were associated with malnutrition. In logistic regression analysis mainly patient
      related factors predicted malnutrition: impaired functioning (OR 3.71, 95% CI
      2.76-4.99), swallowing difficulties (OR 3.03, 95% CI 2.10-4.37), dementia (OR
      2.06, 95% CI 1.45-2.93), constipation (OR 1.84, 95% CI 1.38-2.47), but also
      eating less than half of the offered food portion (OR 3.03, 95% CI 2.21-4.15).
      CONCLUSIONS: Although internal factors explain most about the poor nutritional
      status of aged residents in nursing homes, the factors related to nutritional
      care need further investigation to clarify their role in maintaining the
      nutritional status of aged residents.

PMID- 15744329
TI  - Determination of gene organization in the human IGHV region on single
      chromosomes.
AB  - Organization of the IGHV genes (n=108) on single human chromosomes has been
      determined by detecting these sequences in single sperm using multiplex PCR
      amplification followed by microarray detection. A total of 374 single sperm
      samples from five Caucasian males were studied. Three deletion/insertion
      polymorphisms (Del I-Del III) with deletion allele frequencies ranging from 0.1
      to 0.3 were identified. Del I is a previously reported polymorphism affecting
      three IGHV genes (IGHV1-8, IGHV3-9, and IGHV2-10). Del II affects a region 2-18
      kb containing two pseudogenes IGHV(II)-28.1 and IGHV3-29, and Del III spans
      approximately 21-53 kb involving genes IGHV4-39, IGHV7-40, IGHV(II)-40-1, and
      IGHV3-41. Deletion alleles of both Dels II and III were found in a heterozygous
      state, and therefore, could not be easily detected if haploid samples were not
      used in the study. Results of the present study indicate that
      deletions/insertions together with other possible chromosomal rearrangements may
      play an important role in forming the genetic structure of the IGHV region, and
      may significantly contribute to antibody diversity. Since these three
      polymorphisms are located within or next to the 3' half of the IGHV region, they
      may have an important role in the expressed IGHV gene repertoire during immune
      response.

PMID- 15744330
TI  - Incidence of extragenital vascular disease in patients with erectile dysfunction
      of arterial origin.
AB  - This research was carried out to evaluate the prevalence of carotid and/or lower
      limb artery abnormalities in patients with arterial erectile dysfunction (ED). To
      this end, patients with ED (Andrology Unit) or suspected peripheral
      atherosclerosis (Angiology Unit) underwent an independent and parallel echo
      Duplex examination. The Andrology Unit examined 167 patients with ED of different
      etiologies: 52 of them had penile artery insufficiency and consequently their
      carotids and lower limb arteries had to be evaluated by means of echo-Doppler. In
      all, 36 out of the 46 patients with nonarterial organic ED and 22 out of the 69
      patients with nonorganic ED underwent the same evaluation and served as controls.
      The Angiology Unit enrolled 457 ED patients who initially underwent echo-Doppler
      for suspected carotid and/or arterial leg atherosclerosis and subsequently
      dynamic echo-Doppler. Isolated penile artery insufficiency was found in 23.1 and
      25% of the patients evaluated in the Angiology and Andrology Units, respectively.
      The remaining patients were shown to have ED associated with an atheroma or
      marked intima-media thickness of the carotid vessels and/or of leg arteries. The
      frequency of penile arterial insufficiency and of carotid and/or lower limb
      artery abnormalities was significantly higher (P < 0.01) compared to that found
      in patients with ED of nonarterial organic or psychogenic origin. Both Units
      found that the frequency of penile artery insufficiency and carotid or lower limb
      artery abnormalities was significantly higher than that of penile artery
      insufficiency alone or plus both carotid and lower limb artery abnormalities.
      This study showed that penile artery insufficiency is associated with carotid
      and/or lower limb artery ultrasound abnormalities in about 75% of the cases.
      Therefore, arterial ED may be regarded as a sign of a more generalized
      atherosclerosis.

PMID- 15744331
TI  - Isolated ambulatory hypertension and changes in target organ damage in treated
      hypertensive patients.
AB  - Isolated ambulatory hypertension is a condition characterized by elevated
      ambulatory but normal clinic blood pressure (BP), and has been reported to be
      associated with increased cardiovascular risk in untreated subjects. However,
      little is known about the relationship between this condition and intermediate
      end points such as target organ damage (TOD) in treated hypertensives. We
      investigated the impact of isolated ambulatory hypertension on left ventricular
      hypertrophy (LVH) and microalbuminuria (MA) in a selected sample of treated
      nondiabetic hypertensives with effective and prolonged clinic BP control
      (BP<140/90 mmHg). Clinic BP measurements, routine diagnostic procedures,
      echocardiography and 24-h urine collection for MA, were undertaken in 80 patients
      (mean age 53+/-8 years) with essential hypertension attending our hospital
      outpatient centre at baseline and after an average follow-up of 30 months. At
      follow-up evaluation BP status was assessed by self-measurement of BP and
      ambulatory BP monitoring (ABPM). At the follow-up visit, 51 out of 80 patients
      (63.7%) reached a BP control according to ABP (average daytime BP<132/85 mmHg)
      criteria (group I) whereas the remaining 29 did not (group II); home BP was
      controlled (BP<135/85 mmHg) in all members of group I and in 86% of group II. In
      the overall study population, mean Sokolow voltage, LV mass index (LVMI) and
      urinary albumin excretion (UAE) decreased compared to baseline from 24.1+/-5.0 to
      18.9+/-5.1 mm (P<0.05), 115.6+/-24.1 to 97.7+/-21.6 g/m(2) (P<0.01), 11.8+/-23.7
      to 5.8+/-14.9 mg/24 h (P<0.05), respectively. The prevalence of ECG LVH, altered
      LV patterns and MA fell from 7.5 to 2.5% (P=NS), from 45 to 25 (P<0.01) and from
      13.7 to 5.1% (P<0.05), respectively. However, when data were analysed separately
      for the two groups a significant decrease of echo LVH and MA was found only in
      patients with controlled ABP. LVMI and MA decreased from 117.1+/-23.1 to 95.9+/
      22.1 g/m(2) (P<0.01) and 12.8+/-24.7 to 4.1+/-5.7 mg/24 h (P<0.05) in group I,
      and from 114.1+/-24.8 to 102.3+/-20.3 (P=NS) and 11.9+/-22.1 to 6.3+/-18.1 mg/24
      h (P=NS) in group II. In conclusion, in the present study isolated ambulatory
      hypertension in treated patients is associated with a lack of regression in
      cardiac and extracardiac TOD, suggesting that a tight BP control throughout the
      24 h plays a key role in lowering hypertension-induced structural and functional
      alterations at cardiac and renal level.

PMID- 15744332
TI  - Ambulatory blood pressure, left ventricular mass and vascular phenotypes in
      relation to the endothelial nitric oxide synthase gene Glu298Asp and intron 4
      polymorphisms in a population-based family study.
AB  - Reduced nitric oxide production is associated with pathological changes in the
      cardiovascular system. In a study of randomly chosen families, we analysed the
      relationship between two polymorphisms (Glu298Asp and intron 4) of the
      endothelial nitric oxide synthase (eNOS) and ambulatory blood pressure (ABP),
      left ventricular mass index (LVMI) and vascular phenotypes. The study population
      consisted of 127 parents and 167 offspring. All subjects underwent 24 h ABP
      monitoring using a SpaceLabs 90207 device. 2D and M-mode echocardiograms were
      obtained. Pulse wave velocity between the common carotid and femoral artery was
      measured with the Complior device, and the carotid intima-media thickness (IMT)
      was assessed by ultrasound. For statistical analysis, covariables and
      correlations between relatives were taken into account. The frequency of
      genotypes was as follows: for Glu298Asp: 55.1%-Glu/Glu, 40.1%-Glu/Asp and 4.8%
      Asp/Asp; for intron 4: 65.0%-4 b/b, 33.3%-4 b/a and 1.7%-4 a/a, being in Hardy
      Weinberg equilibrium (P > or = 0.29). There was no relationship between the eNOS
      gene polymorphisms and ABP or LVMI either in parents or their offspring. Among
      parents, carriers of the 298Asp allele had higher IMT values as compared with
      Glu/Glu homozygotes (0.94 vs 0.70 mm; P = 0.007). Among offspring, there was a
      similar tendency (0.60 vs 0.53 mm; P = 0.10), which was confirmed by transmission
      disequilibrium tests for quantitative variables (P > or = 0.07). Our findings
      indicate that the Glu298Asp polymorphism of eNOS identifies patients with larger
      carotid IMT, also in younger subjects.

PMID- 15744333
TI  - Angiotensin-II receptor blockers: benefits beyond blood pressure reduction?
AB  - Effective treatment of hypertension is essential to reduce the risk of renal and
      cardiovascular (CV) morbidity. The risks associated with hypertension are
      modulated by the presence of other factors. This has prompted the quest for
      agents that have benefits beyond blood pressure (BP) lowering. The angiotensin II
      receptor blocker (ARB) class of antihypertensive agents represents an important
      addition to the therapeutic options for elevated BP. Their ability to control BP
      is equivalent to existing therapies and there is a considerable and mounting
      evidence-base for their ability to reduce hypertension-associated target organ
      damage and comorbidities. Studies show that ARBs have clinical benefits across
      the spectrum of disease severity. In particular, recent large studies have
      demonstrated that these benefits extend to patients with conditions predisposing
      to CV events, such as diabetes, left ventricular hypertrophy and
      microalbuminuria, and where risk factors coexist. Data from these studies suggest
      that the CV protective effects of ARBs are at least, in part, independent from
      the BP lowering action. In addition, ARBs are extremely well tolerated, and
      strong evidence suggests that compliance with therapy--a key factor in achieving
      adequate BP control--with ARBs is higher than with other antihypertensive agents.
      Furthermore, flexible dosing and good tolerability profile mean that, where
      necessary, ARBs can be combined with other classes of antihypertensive agents to
      achieve adequate BP control and reduce the risk of hypertension-associated
      morbidity.

PMID- 15744334
TI  - Transiently elevated diastolic blood pressure is associated with a gender
      dependent effect on cardiovascular risk.
AB  - We assessed the morbidity and mortality of subjects with transiently elevated
      diastolic pressure in the General Practice Hypertension Study Group (GPHSG)
      population. A total of 23 578 patients (aged 18-65 years) from seven UK general
      practices were screened in 1974 for a diastolic blood pressure (DBP4) of > or =
      90 mmHg. Two further readings of DBP4 determined hypertensive (either DBP4 > or =
      90 mmHg) or transient hypertensive (both DBP4 < 90 mmHg) status. Transients (n =
      850) were matched with normotensive controls (n = 824) and risk ratios calculated
      over a mean follow-up of 18.7 years. Rescreening was conducted in six of the
      practices (n = 20 942) after 7.7 years. Male transients had a higher relative
      hazard for cardiovascular mortality than controls (11.8%, 8.6%, adjusted relative
      hazard 1.59, P = 0.056). Female transients had a lower relative hazard for
      cardiovascular mortality than controls (3.6%, 5.4%, adjusted relative hazard
      0.39, P = 0.018). In all, 422 patients with transient hypertension were
      rescreened along with 367 matched controls. Significantly more transients were on
      antihypertensive treatment compared with their controls (odds ratio (OR) [95%
      CI]) for both male (4.2 [1.6-11.1]) and female patients (2.4 [1.0-5.56]) and more
      untreated female transients developed hypertension. Male transients had a higher
      rates of diabetes mellitus (adj OR = 5.1, P = 0.04) and stroke (adj OR 15.9, P =
      0.03). This study has shown that transiently elevated DBP in GPHSG is associated
      with a significantly higher risk of later hypertension in men and women and of
      diabetes, stroke and cardiovascular mortality in men. Women with this condition
      have a significantly lower cardiovascular mortality.

PMID- 15744335
TI  - Gadd45a acts as a modifier locus for lymphoblastic lymphoma.
AB  - GADD:45a-/- and p53-/- mice and cells derived from them share similar phenotypes,
      most notably genomic instability. However, p53-/- mice rapidly develop a variety
      of neoplasms, while Gadd45a-/- mice do not. The two proteins are involved in a
      regulatory feedback loop, whereby each can increase the expression or activity of
      the other, suggesting that common phenotypes might result from similar molecular
      mechanisms. Mice lacking both genes were generated to address this issue. Gadd45a
      /-p53-/- mice developed tumors with a latency similar to that of tumor-prone p53
      /- mice. However, while p53-/- mice developed a variety of tumor types, nearly
      all Gadd45a-/-p53-/- mice developed lymphoblastic lymphoma (LBL), often
      accompanied by mediastinal masses as is common in human patients with this tumor
      type. Deletion of Gadd45a in leukemia/lymphoma-prone AKR mice decreased the
      latency for LBL. These results indicate that Gadd45a may act as modifier locus
      for T-cell LBL, whereby deletion of Gadd45a enhances development of this tumor
      type in susceptible mice. Gadd45a is localized to 1p31.1, and 1p abnormalities
      have been described in T-cell lymphomas. Related human tumor samples did not show
      Gadd45a deletion or mutation, although changes in expression could not be ruled
      out.

PMID- 15744336
TI  - Pathology and clinical features of angioimmunoblastic T-cell lymphoma after
      successful treatment with thalidomide.

PMID- 15744337
TI  - High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related
      solid immunoblastic/plasmablastic diffuse large B-cell lymphoma.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) is known to be associated with two
      distinct lymphoproliferative disorders: primary effusion lymphoma (PEL) and
      multicentric Castleman disease (MCD)/MCD-associated plasmablastic lymphoma. We
      here report a high incidence of KSHV infection in solid HIV-associated
      immunoblastic/plasmablastic non-Hodgkin's lymphomas (NHLs), in patients lacking
      effusions and without evidence of (prior) MCD. Within a cohort of 99 HIV-related
      NHLs, 10 cases were found to be KSHV positive on the basis of immunostaining for
      KSHV LNA-1 as well as KSHV-specific polymerase chain reaction. All but one of the
      tumors coexpressed Epstein-Barr virus. Interestingly, all KSHV-positive cases
      belonged to a distinctive subgroup of 26 diffuse large B-cell lymphomas
      characterized by the expression of CD138 (syndecan-1) and
      plasmablastic/immunoblastic morphology. These KSHV-positive lymphomas were
      preceded by Kaposi sarcoma in 60% of the patients and involved the
      gastrointestinal tract in 80%. Our results indicate that KSHV infection is not
      restricted to PEL and MCD; it is also common (38%) in HIV-related solid
      immunoblastic/plasmablastic lymphomas.

PMID- 15744338
TI  - Acute myeloid leukemias with recurrent genetic abnormalities: frequent assessment
      of minimal residual disease and treatment of molecular relapse with chemotherapy.

PMID- 15744339
TI  - The CD107 mobilization assay: viable isolation and immunotherapeutic potential of
      tumor-cytolytic NK cells.

PMID- 15744340
TI  - CD56dimCD16neg cells are responsible for natural cytotoxicity against tumor
      targets.
AB  - The activation of natural killer (NK) cells leads to degranulation and secretion
      of cytotoxic granula. During this process, the lytic granule membrane protein
      CD107a becomes detectable at the cell surface. Based on this phenomenon, we have
      analyzed by a novel flow cytometry-based assay, the number and phenotype of NK
      cells responding to tumor targets. Using human leukemia and lymphoma cell lines,
      we observed a close correlation between CD107a surface expression and target cell
      lysis, indicating that NK cell cytotoxicity can be assessed by this method. The
      number of degranulating NK cells was closely related to the ratio of effector and
      target cells and showed a maximum at a ratio of 1:1. Moreover, we were able to
      show that the population of CD56(dim)/CD16(neg) NK cells is primarily responsible
      for the cytotoxic activity against tumor targets whereas neither
      CD56(dim)/CD16(pos) nor CD56(bright) NK cells degranulated in response to the
      cell lines. Our results indicate that the CD107a assay represents a promising new
      method for the quantification and characterization of cells exhibiting natural
      cytotoxicity.

PMID- 15744342
TI  - PRV-1 and its correlation with treatments and disease status in 210 patients with
      polycythemia vera and essential thrombocythemia.

PMID- 15744341
TI  - Expression pattern of intracellular leukocyte-associated proteins in primary
      mediastinal B cell lymphoma.
AB  - Two microarray studies of mediastinal B cell lymphoma have shown that this
      disease has a distinct gene expression profile, and also that this is closest to
      the pattern seen in classical Hodgkin's disease. We reported previously an
      immunohistologic study in which the loss of intracellular B cell-associated
      signaling molecules in Reed-Sternberg cells was demonstrated, and in this study
      we have investigated the expression of the same components in more than 60
      mediastinal B cell lymphomas. We report that these signaling molecules are
      frequently present, and in particular that Syk, BLNK and PLC-gamma2 (absent from
      Reed-Sternberg cells) are present in the majority of mediastinal B cell
      lymphomas. The overall pattern of B cell signaling molecules in this disease is
      therefore closer to that of diffuse large B cell lymphoma than to Hodgkin's
      disease, and is consistent with a common cell of origin as an explanation of the
      similar gene expression profiles.

PMID- 15744343
TI  - ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in
      acute promyelocytic leukemia cells.
AB  - Acute promyelocytic leukemia (APL) is uniquely sensitive to treatment with all
      trans retinoic acid (ATRA), which results in the expression of genes that induce
      the terminal granulocytic differentiation of the leukemic blasts. Here we report
      the identification of two ATRA responsive genes in APL cells, ID1 and ID2. These
      proteins act as antagonists of basic helix-loop-helix (bHLH) transcription
      factors. ATRA induced a rapid increase in ID1 and ID2, both in the APL cell line
      NB4 as well as in primary patient cells. In addition, a strong downregulation of
      E2A was observed. E2A acts as a general heterodimerization partner for many bHLH
      proteins that are involved in differentiation control in various tissues. The
      simultaneous upregulation of ID1 and ID2, and the downregulation of E2A suggest a
      role for bHLH proteins in the induction of differentiation of APL cells following
      ATRA treatment. To test the relevance of this upregulation, ID1 and ID2 were
      overexpressed in NB4 cells. Overexpression inhibited proliferation and induced a
      G0/G1 accumulation. These results indicate that ID1 and ID2 are important
      retinoic acid responsive genes in APL, and suggest that the inhibition of
      specific bHLH transcription factor complexes may play a role in the therapeutic
      effect of ATRA in APL.

PMID- 15744344
TI  - Transplantable cell lines generated with NUP98-Hox fusion genes undergo leukemic
      progression by Meis1 independent of its binding to DNA.
AB  - Hox genes have been identified in chromosomal translocations involving the
      nucleoporin gene NUP98. Though the resulting chimeric proteins directly
      participate in the development of leukemia, the long latency and monoclonal
      nature of the disease support the requirement for secondary mutation(s), such as
      those leading to overexpression of Meis1. Models to identify such events and to
      study leukemic progression are rare and labor intensive. Herein, we took
      advantage of the strong transforming potential of NUP98-HOXD13 or NUP98-HOXA10 to
      establish preleukemic myeloid lines from bone marrow cells that faithfully
      replicate the first step of Hox-induced leukemogenesis. These lines contain early
      granulomonocytic progenitors with extensive in vitro self-renewal capacity, short
      term myeloid repopulating activity and low propensity for spontaneous leukemic
      conversion. We exploit such lines to show that Meis1 efficiently induces their
      leukemic progression and demonstrate a high frequency of preleukemic cells in the
      cultures. Furthermore, we document that the leukemogenic potential of Meis1 is
      independent of its direct binding to DNA and likely reflects its ability to
      increase the repopulating capacity of the preleukemic cells by increasing their
      self-renewal/proliferative capacity. The availability of lines with repopulating
      potential and capacity for leukemic conversion should open new avenues for
      understanding progression of Hox-mediated acute myeloid leukemia.

PMID- 15744345
TI  - No prognostic effect of additional chromosomal abnormalities in children with
      acute lymphoblastic leukemia and 11q23 abnormalities.
AB  - This study characterized the additional chromosomal abnormalities (ACA)
      associated with 11q23 rearrangements in 450 infants and children with acute
      lymphoblastic leukemia (ALL) and examined the impact of these ACA on survival.
      Overall, 213 (47%) cases had ACA but the incidence varied according to patient
      age and 11q23 subgroup. Infants and patients with t(4;11)(q21;q23) had the lowest
      incidence of ACA (50/182 (27%) and 57/216 (26%) respectively), whereas patients
      with del(11)(q23) had the highest incidence (66/93 (71%)). Del(11)(q23)
      abnormalities were heterogeneous and occasionally secondary to
      t(9;22)(q34;q11.2). Thus, patients with del(11)(q23) comprised a separate
      biological entity, which was clearly distinct from those with an 11q23
      translocation. The most frequent specific ACA were trisomy X (n = 38), abnormal
      12p (n = 32), abnormal 9p (n = 28) and del(6q) (n = 19). The presence of ACA did
      not change the 5 year event-free survival estimates among children (56% (95% Cl
      46-65%) vs 62% (54-69%)) or infants (22% (15-29%) vs 18% (9-29%)), nor when the
      different 11q23 subgroups were analyzed separately. This study has conclusively
      demonstrated that there is no prognostic effect of secondary chromosomal changes
      in association with 11q23 abnormalities in childhood ALL. However,
      characterization of these ACA is important to determine their potential role in
      initiation of MLL driven leukemogenesis.

PMID- 15744346
TI  - Effector gammadelta T cells and tumor cells as immune targets of zoledronic acid
      in multiple myeloma.
AB  - The aim of this study was to investigate the in vitro immunomodulatory effects of
      zoledronic acid (Zol) on peripheral blood Vgamma9/Vdelta2 (gammadelta) T cells of
      normal donors and multiple myeloma (MM) patients. gammadelta T cells were
      stimulated with Zol and low doses of interleukin-2 (IL-2), and then analyzed for
      proliferation, cytokine production, and generation of effector activity against
      myeloma cell lines and primary myeloma cells. Proliferation of gammadelta T cells
      was observed in 100% of normal donors and 50% of MM patients. gammadelta T cells
      produced IFN-gamma, surface mobilized the CD107a and CD107b antigens, and exerted
      direct cell-to-cell antimyeloma activity irrespective of the ability to
      proliferate to Zol and IL-2. The memory phenotype was predominant in the MM
      gammadelta T cells that proliferated in response to Zol (responders), whereas
      effector cells were predominant in those that did not (nonresponders). Zol
      induced antimyeloma activity through the monocyte-dependent activation of
      gammadelta T cells and by enhancing the immunosensitivity of myeloma cells to
      gammadelta T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl
      CoA reductase, completely abrogated this antimyeloma activity.

PMID- 15744347
TI  - Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia
      cells.
AB  - Farnesyltransferase inhibitors (FTIs) are currently under investigation for
      leukemia treatment. We evaluated the FTI manumycin A (manumycin) in two myeloid
      leukemia cell lines (U937 and HL-60). Manumycin induced nitric oxide production
      and apoptosis of the leukemia cells. Nitric oxide or other reactive oxygen
      species may induce oxidative DNA damage, and the number of apurinic sites
      increased after manumycin treatment, which was reversed by concurrent treatment
      with N-acetyl-L-cysteine. Since repair of DNA damage is important to cell
      survival, we hypothesized that methoxyamine, an inhibitor of base-excision
      repair, would enhance the antineoplastic effect of manumycin. The combination of
      manumycin and methoxyamine resulted in enhanced apoptosis by six criteria
      increased annexin V binding, release of mitochondrial cytochrome c into the
      cytosol, activation of caspase-9, activation of caspase-3, specific cleavage of
      poly-adenosyl ribose polymerase, and increase in the sub-G1 cell cycle fraction.
      The drug combination enhanced inhibition on the soft agar clonogenic assay and on
      the formazan dye cell viability assay. The effects of manumycin or manumycin plus
      methoxyamine on apoptosis were blocked by N-acetyl-L-cysteine, and partially by
      nitric oxide synthase inhibitors or scavenger of peroxide. We conclude that
      methoxyamine enhances manumycin-induced apoptosis in myeloid leukemia cells.

PMID- 15744348
TI  - Value of intravenous 6-mercaptopurine during continuation treatment in childhood
      acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a
      randomized phase III trial (58881) of the EORTC CLG.
AB  - Between November 1990 and November 1996, EORTC Children Leukemia Group conducted
      a randomized trial in de novo acute lymphoblastic leukemia and lymphoblastic non
      Hodgkin's lymphoma patients using a Berlin-Frankfurt-Munster protocol to evaluate
      the monthly addition of intravenous 6-mercaptopurine (i.v. 6-MP) (1 g/m(2)) to
      conventional continuation therapy comprising per oral MTX weekly and 6-MP daily.
      Only during the first 18 months of the randomization period, 6-MP p.o. was
      interrupted for 1 week after each i.v. 6-MP. A total of 877 patients was
      randomized to either no i.v. 6-MP (Arm A) or additional i.v. 6-MP (Arm B). A
      total of 217 relapses (91 in Group A vs 128 in Group B) and 13 deaths in CR (5 vs
      8) were reported; a total of 134 patients (55 vs 79) died. The median follow-up
      was 7.6 years. At 8 years, the disease-free survival rate was lower (P=0.005) in
      Arm B (69.1% (s.e.=2.2%)) than in Arm A (77.9% (s.e.=2.0%)), and the hazard ratio
      was 1.45 (95% CI 1.12-1.89). In conclusion, as delivered in this study, i.v. 6-MP
      was detrimental to event-free survival.

PMID- 15744349
TI  - Purity for clarity: the need for purification of tumor cells in DNA microarray
      studies.
AB  - It is now well established that gene expression profiling using DNA microarrays
      can provide novel information about various types of hematological malignancies,
      which may lead to identification of novel diagnostic markers. However, to
      successfully use microarrays for this purpose, the quality and reproducibility of
      the procedure need to be guaranteed. The quality of microarray analyses may be
      severely reduced, if variable frequencies of nontarget cells are present in the
      starting material. To systematically investigate the influence of different types
      of impurity, we determined gene expression profiles of leukemic samples
      containing different percentages of nonleukemic leukocytes. Furthermore, we used
      computer simulations to study the effect of different kinds of impurity as an
      alternative to conducting hundreds of microarray experiments on samples with
      various levels of purity. As expected, the percentage of erroneously identified
      genes rose with the increase of contaminating nontarget cells in the samples. The
      simulations demonstrated that a tumor load of less than 75% can lead to up to 25%
      erroneously identified genes. A tumor load of at least 90% leads to
      identification of at most 5% false-positive genes. We therefore propose that in
      order to draw well-founded conclusions, the percentage of target cells in
      microarray experiment samples should be at least 90%.

PMID- 15744350
TI  - Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion
      proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia.
AB  - We analyzed the TS-2 acute lymphoblastic leukemia (ALL) cell line that contains a
      t(1;19)(q23;p13.3) but lacks E2A-PBX1 fusion typically present in leukemias with
      this translocation. We found that the t(1;19) in TS-2 fuses the 19p13 gene DAZAP1
      (Deleted in Azoospermia-Associated Protein 1) to the 1q23 gene MEF2D (Myocyte
      Enhancer Factor 2D), leading to expression of reciprocal in-frame DAZAP1/MEF2D
      and MEF2D/DAZAP1 transcripts. MEF2D is a member of the MEF2 family of DNA binding
      proteins that activate transcription of genes involved in control of muscle cell
      differentiation, and signaling pathways that mediate response to mitogenic
      signals and survival of neurons and T-lymphocytes. DAZAP1 is a novel RNA binding
      protein expressed most abundantly in the testis. We demonstrate that MEF2D/DAZAP1
      binds avidly and specifically to DNA in a manner indistinguishable from that of
      native MEF2D and is a substantially more potent transcriptional activator than
      MEF2D. We also show that DAZAP1/MEF2D is a sequence-specific RNA-binding protein.
      MEF2D has been identified as a candidate oncogene in murine retroviral
      insertional mutagenesis studies. Our data implicate MEF2D in human cancer and
      suggest that MEF2D/DAZAP1 and/or DAZAP1/MEF2D contribute to leukemogenesis by
      altering signaling pathways normally regulated by wild-type MEF2D and DAZAP1.

PMID- 15744351
TI  - Significant reduction of the hybrid BCR/ABL transcripts after induction and
      consolidation therapy is a powerful predictor of treatment response in adult
      Philadelphia-positive acute lymphoblastic leukemia.
AB  - Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has a
      dismal prognosis. We prospectively evaluated minimal residual disease (MRD) by
      measuring BCR/ ABL levels with a quantitative real-time PCR procedure after
      induction and after consolidation in 45 adults with Ph+ ALL who obtained complete
      hematological remission after a high-dose daunorubicin induction schedule. At
      diagnosis, the mean BCR-ABL/GUS ratio was 1.55 +/- 1.78. A total of 42 patients
      evaluable for outcome analysis were operationally divided into two MRD groups:
      good molecular responders (GMRs; n = 28) with > 2 log reduction of residual
      disease after induction and > 3 log reduction after consolidation therapy, and
      poor molecular responders (PMRs; n = 14) who, despite complete hematological
      remission, had a higher MRD at both time points. In GMR, the actuarial
      probability of relapse-free, disease-free and overall survival at two years was
      38, 27 and 48%, respectively, as compared to 0, 0 and 0% in PMR (P = 0.0035,
      0.0076 and 0.0026, respectively). Salvage therapy induced a second sustained
      complete hematological remission in three GMR patients, but in no PMR patient.
      Our data indicate that, as already shown in children, adult Ph+ ALL patients have
      a heterogeneous sensitivity to treatment, and that early quantification of
      residual disease is a prognostic parameter in this disease.

PMID- 15744352
TI  - Allogeneic hematopoietic stem cell transplantation provides sustained long-term
      survival for patients with adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a distinct peripheral T-cell neoplasm
      that is highly resistant to chemotherapy. Several groups, including ours, have
      reported encouraging results of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) for patients with ATLL. To confirm our previous
      report and to establish the basis for a phase II clinical study, we analyzed 40
      allo-HSCT for acute and lymphoma types of ATLL in seven institutions in Japan
      between 1997 and 2002. All evaluable cases entered complete remission (CR) after
      allo-HSCT and the median survival time was 9.6 months for all patients. The
      estimated 3-year overall and relapse-free survival, and disease relapse were
      45.3, 33.8 and 39.3%, respectively. Among 10 cases with ATLL relapse, five cases
      achieved CR again: three by the reduction or cessation of immunosuppressive
      agents, which suggested a graft-versus-ATLL (GvATLL) effect. However, univariate
      or multivariate analysis did not show any benefit of graft-versus-host disease
      (GVHD) on the prevention of relapse. These results suggested that allo-HSCT was
      effective for some patients with aggressive ATLL, and that the GvATLL effect
      could be achieved even without GVHD. A new phase II trial to test the efficacy of
      allo-HSCT for ATLL is warranted.

PMID- 15744353
TI  - AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B
      chronic lymphocytic leukemia cells: interference with the Akt/NF-kappaB survival
      pathway.
AB  - Clinical treatment of B-cell chronic lymphocytic leukemia (B-CLL) is limited by
      the progressive drug resistance and nonselectivity of most drugs towards
      malignant cells. Depsipeptides are present in certain bacteria and display potent
      antitumor activity. We have studied the effect of the novel cyclodepsipeptide
      AT514 (serratamolide) from Serratia marcescens on B-CLL cell viability. AT514
      induced apoptosis of B-CLL cells from the 21 patients studied, as confirmed by
      Annexin-V binding and nuclei condensation, with an average IC50 of 13 microM.
      AT514 was effective in those B-CLL cases resistant to fludarabine, but had no
      effect on normal PBL. AT514 preferentially activated the intrinsic apoptotic
      pathway, as evidenced by loss of mitochondrial membrane potential, release of
      cytochrome c and activation of caspase-9 and -3, but not of caspase-8.
      Importantly, AT514 interfered with phosphatidylinositol-3 kinase and protein
      kinase C survival signals since it increased the apoptotic effect of LY294002 and
      Bisl inhibitors, and induced Akt dephosphorylation at Ser 473. AT514 also
      decreased NF-kappaB activity by dramatically reducing the levels of p65 in B-CLL.
      This was confirmed on functional assays using NF-kappaB-luc-transfected Raji
      cells and transgenic mice. Our results establish that AT514 induces apoptosis of
      primary B-CLL cells and could be useful for clinical treatment of this
      malignancy.

PMID- 15744354
TI  - Absence of ATM hypermethylation in mantle cell and follicular lymphoma.

PMID- 15744355
TI  - Levels of soluble CD137 are enhanced in sera of leukemia and lymphoma patients
      and are strongly associated with chronic lymphocytic leukemia.

PMID- 15744356
TI  - CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor
      prognosis.
AB  - Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood.
      Although therapeutical advances have been achieved, some ALL subgroups still fare
      poorly. CD1d is a monomorphic molecule that provides a suitable target for
      immunotherapy in view of the characterization of a glycolipid, alpha
      galactosylceramide (alpha-GalCer), capable of being presented to CD1d-restricted
      T cells with cytotoxic potential. We investigated CD1d expression in 80 pediatric
      B-cell precursor (BCP) ALL cases defined according to immunophenotype,
      cytogenetic features and age at onset. CD1d was detected on ALL cells in 15% of
      the patients. CD1d+ ALLs were significantly associated with infant leukemia, pro
      B phenotype and mixed-lineage leukemia (MLL)/AF4 gene rearrangement. Accordingly,
      overall survival of patients with CD1d+ ALL was significantly shorter. CD1d+
      leukemic blasts were able to present alpha-GalCer via CD1d to cytotoxic CD1d
      restricted T cells, which induced apoptosis of ALL cells that was inhibited by
      mAb to CD1d. CD1d+ blasts loaded with alpha-GalCer elicited cytokine secretion by
      CD1d-restricted T cells. Analysis of bone marrow (BM) cells derived from normal
      donors revealed that CD19+/CD1d+ cells were mostly mature B lymphocytes. However,
      a minority of BCPs expressed CD1d. Thus, expression of CD1d in ALL cases heralds
      an adverse prognosis but may provide a therapeutic tool.

PMID- 15744357
TI  - Heart failure and first dose hypotension after angiotensin converting enzyme
      inhibitors.
AB  - The first-dose induced decrease in blood pressure in some patients following the
      administration of ACE inhibitors is a fact causing some concern among clinicians
      prescribing these drugs. However, an overview of clinical trials and the authors'
      own experience clearly point to the possibility of reducing the incidence and/or
      severity of first-dose hypotension. Apart from appropriate clinical measures to
      be taken, the choice of the ACE inhibitor seems to be of crucial importance as
      some (fosinopril, perindopril) produce less hypotension than others. Thus, with
      due circumspection, ACE inhibitors can safely retain their position as the
      cornerstone of the treatment of chronic heart failure.

PMID- 15744358
TI  - Can we identify patients with carotid occlusion who would benefit from EC/IC
      bypass? Review.
AB  - Occlusion of the internal carotid artery (CAO) is associated with a high
      mortality rate and frequent disability in survivors. Even in patients with good
      clinical recovery there is a high risk of recurrent stroke, mainly in those with
      impaired cerebral vasomotor reactivity (CVR). Current evidence based therapeutic
      options for patients with symptomatic CAO include antithrombotic medication and
      control of vascular risk factors. For stenosis of the contralateral internal or
      ipsilateral external carotid artery, endarterectomy or percutaneous transluminal
      angioplasty may be considered. Ongoing symptoms may cease after tapering
      antihypertensive medications. Extracranial to intracranial (EC/IC) arterial
      bypass surgery has been used since 1967 in patients with CAO. However, the
      international randomized EC/IC Bypass Study (1985) failed to confirm the
      effectiveness of EC/IC bypass for preventing cerebral ischemia in patients with
      symptomatic CAO when compared to those assigned to the best medical care.
      Nevertheless, the conclusion of the EC/IC Bypass Study has several objections and
      downfalls. Since then, there has been a revival of interest in cerebral
      revascularization procedures owing to the substantial progression of surgical
      techniques and the use of more advanced diagnostic methods. Thus, it has recently
      been reported that EC/IC bypass surgery can be useful in preventing stroke in
      patients with hemodynamic compromise. The main problem is to identify the small
      subgroup of surgical candidates. Presently, single photon emission computed
      tomography (SPECT), positron emission tomography (PET), transcranial Doppler
      sonography (TCD), computed tomography (CT) with administration of (133)Xe,
      perfusion CT, near infrared spectroscopy (NIRS), and functional magnetic
      resonance imaging (fMRI) are being used for this purpose.

PMID- 15744360
TI  - The antioxidant acetylcysteine reduces oxidative stress by decreasing level of
      AOPPs.
AB  - Oxidative stress and especially its connection with many diseases has been
      discussed much recently. Among markers of oxidative stress there appear new and
      quite specific ones called advanced oxidation protein products (AOPPs). We tried
      to influence the level of AOPPs by an antioxidant therapy with N-acetylcysteine.
      Fourteen individuals with many cardiovascular risk factors were examined. All
      these patients were administered acetylcysteine (NAC) 600 mg/day orally during 20
      days. Before starting the therapy we determined AOPP, albumin cobalt binding
      (ACB), glucose, creatinine, urea, ALT, AST, cholesterol, LDL, HDL and
      triglycerides values in peripheral venous blood in all individuals. After
      finishing our intervention we determined AOPP, ACB and glucose level again. Our
      results show a statistically significant decrease in AOPP levels after 20-day N
      acetylcysteine therapy (medians, initially 82.2, at study end 74.3 umol/l, p =
      0.039). We demonstrate a significant decrease in AOPP levels after 20-day N
      acetylcysteine therapy in dose 600 mg/day.

PMID- 15744359
TI  - Molecular diagnosis of prosthetic joint infection. A review of evidence.
AB  - Prosthetic joint infection (PJI) diagnosis includes several classes of
      verification. Among them, only a few have a stronger independent value, namely
      intraarticular purulence and communicating fistulas. Other diagnostic methods
      require careful test combinations, analysis, and interpretation. Molecular based
      techniques using the polymerase chain reaction (PCR) seem to be a promising PJI
      diagnostic modality due to its excellent sensitivity, specificity, positive
      predictive value, and speed. Most of the recent reviewers are in agreement that
      molecular diagnosis has enough potential for future application in orthopaedics
      even if there are only a few heterogeneous studies fully supporting this concept.
      Conversely, at least one study has been published with significantly worse
      results (sensitivity and specificity less than 0.75). The lack of supporting
      evidence in the published studies may be closely related to varying PCR
      laboratory procedures, inappropriate reference standards, and other
      methodological shortcomings among research centers. It is not yet justifiable to
      firmly include molecular methods into the present PJI diagnostic schemes. The
      orthopaedic community must await the results of well-organized ongoing studies
      before considering inclusion of molecular diagnostics as a PJI diagnostic method.
      The aim of this paper was to make a survey of current PJI molecular diagnostic
      techniques in orthopaedics.

PMID- 15744361
TI  - Microtubule disarray in primary cultures of human hepatocytes inhibits
      transcriptional activity of the glucocorticoid receptor via activation of c-jun N
      terminal kinase.
AB  - The human glucocorticoid receptor (hGR) plays a pivotal role in cellular
      processes such as development, differentiation, homeostasis, immune response and
      in regulation of xenobiotic metabolism. It has been demonstrated recently that
      colchicine inhibits hGR transcriptional activity in primary cultures of human
      hepatocytes by a mechanism involving impairment of hGR nucleo-cytoplasmic
      shuttling. In the present work, we investigated the role of the nuclear factor
      kappa B (NFkappaB) and c-jun-N-terminal kinase (JNK), the functional hGR
      antagonists, in this process. We found that microtubule disarray caused by
      colchicine, vincristine or nocodazole does not activate NFkappaB in human
      hepatocytes as revealed by p50 and p65 subunits nuclear translocation. On the
      other hand, we demonstrate that JNK mediates hGR transcriptional inhibition by
      microtubules disarray, because a specific inhibitor of JNK, 1,9-pyrazoloanthrone
      (SP600125), partially blocked tyrosine aminotransferase mRNA suppression due to
      colchicine treatment. In conclusion, JNK is at least partly involved in hGR
      transcriptional inhibition by colchicine in human hepatocytes, while NFkappaB
      involvement is doubtful.

PMID- 15744362
TI  - N-formyl-Met-Leu-Phe-induced oxidative burst in DMSO-differentiated HL-60 cells
      requires active Hsp90, but not intact microtubules.
AB  - In this study we examined whether microtubules and heat shock protein 90 (Hsp90)
      are involved in phorbol myristate acetate (PMA) and N-formyl-Met-Leu-Phe (fMLP)
      induced oxidative burst in DMSO-differentiated HL-60 cells. Our results showed
      that microtubule interfering agents, paclitaxel (1-5 microM), colchicine (1-100
      microM), nocodazole (1-20 microM), and vincristine (1-50 microM), did not affect
      either PMA or fMLP-induced oxidative burst. In contrast, radicicol, an inhibitor
      of Hsp90, inhibited fMLP-induced oxidative burst in time and concentration
      dependent manner where IC50 value for 30 min pre-incubation was 16.5 +/- 3.5
      microM radicicol. We conclude that both PMA and fMLP-induced oxidative burst in
      DMSO-differentiated HL-60 cells is microtubule-independent while the latter
      requires Hsp90 activity.

PMID- 15744363
TI  - ERPs to words--effect of gender and site of recording electrode.
AB  - Event-related potentials (ERPs) to word stimuli were registered in 20 twenty-one
      year-old students (7 males and 13 females) of the Faculty of Medicine of Palacky
      University. In an ideal case in the first 800 ms after the onset of stimulus ERP
      consists of three clear positive and four negative waves. The amplitude of some
      waves of ERPs shows a high degree of inter-individual variability. It was also
      revealed that the latency and amplitude of some ERPs waves to word stimuli
      depends on the gender and on the site of the registration electrode on the scalp
      of the subject. Latencies of components LP2 and LN4 in all electrodes are shorter
      in females than in males, component LN2 behaves reversely--its latency is shorter
      in males. On the other hand, the amplitude of dependent variables BP2, BN2 and
      PV1 is in most electrodes higher in females than in males--except for the
      amplitude of components BP4 and BN1.

PMID- 15744364
TI  - ERPs to nouns and verbs--congruences and differences.
AB  - The results of the multivariate analysis of variance confirmed statistically
      significant differences in latency and amplitude of some ERPs waves to nouns and
      ERPs to verbs. ERPs to nouns differ from ERPs to verbs by a significantly longer
      latency and greater amplitude of some waves. A comparison of the characteristics
      of ERPs to nouns and ERPs to verbs separately in males and females produced
      basically identical results; in females, however, there are much fewer
      significant differences than in males. Interaction between the site of the
      recording electrode and features of ERPs to words of different word classes
      however could not be demonstrated.

PMID- 15744365
TI  - ERPs to subclasses of nouns and verbs.
AB  - The present findings show the existence of significant differences in latency and
      amplitude of some waves of ERPs to three subclasses of nouns or verbs. Latency
      LP3 of ERPs to action verbs was shorter than latency of the same wave to abstract
      verbs. In nouns the relation was a similar (manipulable objects versus abstract
      ones). The amplitude of early positive components (P1, P2) and BN3 wave also
      depended on semantic attributes of nouns and verbs. Some waves of ERPs to motion
      verbs in our experiment had significantly higher amplitude than the same waves of
      ERPs to nonmanipulable objects. Also revealed was interaction between some ERP
      features and the subject's gender. It was primarily the amplitude of BP2, the
      size of which depended on gender in all cases--BP2 amplitude was significantly
      higher in females then in males. In the other components (BP1, BP4, BN2 and BN4)
      there were fewer significant differences and if they do occurred, then their
      amplitude was higher in males than in females. In some cases, gender also
      affected latency of waves LP2, LN1 and LN4 of ERPs to the same noun or verb
      subclass--latencies of these waves were shorter in females.

PMID- 15744366
TI  - Pharmacokinetics and biodistribution studies of Doxorubicin loaded poly(butyl
      cyanoacrylate) nanoparticles synthesized by two different techniques.
AB  - The aim of the study is to determine and compare the pharmacokinetics and tissue
      distribution of Doxorubicin (Dox) delivered as solution or through nanoparticles
      after intravenous (i.v.) and intraperitoneal (i.p.) injection. Doxorubicin loaded
      poly(butyl cyanoacrylate) nanoparticles were synthesized by dispersion
      polymerization (DP) and emulsion polymerization (EP) techniques. The drug loaded
      DP and EP nanoparticles were administered by i.v. or i.p. routes and the
      respective pharmacokinetics and tissue distribution were determined. Both types
      of nanoparticles significantly enhanced the elimination half-life (T(1/2)), mean
      residence time (MRT) AUC(0-8), AUC(0-infinity) and AUMC(0-8) of Dox in blood
      after i.v. injection. Dox delivered through DP nanoparticles rapidly disappeared
      from blood and distributed to the organs of reticuloendothelial system (RES).
      But, the clearance of Dox delivered through EP nanoparticles from blood was
      slower than this of the DP nanoparticles and Dox solution. After i.p. injection,
      the Dox loaded into DP nanoparticles quickly appeared in blood and undergone
      rapid distribution to the organs of RES, while the Dox loaded into EP
      nanoparticles absorbed slowly into blood and remained in the circulation for
      longer time. The absorption into blood of Dox delivered through DP and EP
      nanoparticles after i.p. injection was relatively rapid and higher than Dox
      solution. The T(1/2), MRT, AUC(0-8), AUC(0-infinity) and AUMC(0-8) of Dox in
      blood were significantly higher and the clearance (Cl) was lower than for the Dox
      solution after i.p. injection. The tissue concentrations of Dox delivered through
      nanoparticles after i.p. injection were significantly lower than after i.v.
      injection. The bioavailability (F) of Dox was greatly enhanced by DP
      (approximately 1.9 fold) and EP nanoparticles (approximately 2.12 fold) compared
      to Dox solution after i.p. injection. EP nanoparticles significantly enhanced the
      bioavailability, MRT, T(1/2), AUC(0-8), AUC(0-infinity) and AUMC(0-8) of Dox than
      DP nanoparticles. This signifies the advantage of EP nanoparticles in increasing
      the elimination half-life of Dox both after i.v. and i.p. injection and enhanced
      bioavailability after i.p. injection, which is expected to improve the
      therapeutic efficacy of Dox and reduce the Dox-associated systemic toxicity.
      Importantly, both DP and EP nanoparticles greatly reduced the distribution of Dox
      to heart both after i.v. and i.p. injection, suggesting their potential in
      reducing Dox-associated cardiotoxicity.

PMID- 15744367
TI  - Molecular-biological analysis of vancomycin-resistant enterococci isolated from a
      community in the Czech Republic.
AB  - OBJECTIVE: To determine the occurrence of vancomycin-resistant enterococci (VRE)
      in a community of the Czech Republic and a molecular-biological analysis of the
      VRE isolated. METHODS: Enterococci were isolated from the rectal swabs of healthy
      people in the Olomouc region (population 300,000), Czech Republic in the period
      of January-December 2003. The molecular-biological analysis of VRE was performed
      by analysis of isolated DNA, which was cleaved by restriction enzyme SmaI and
      separated by pulse field gel electrophoresis (PFGE). RESULTS: A total number of
      5,283 swabs were evaluated and 558 Enterococcus sp. strains were isolated during
      the follow-up period. 9 strains (1.6%) were identified as VRE. Two strains were
      E. faecium phenotype VanA, one strain was E. faecalis phenotype VanB, two strains
      were E. gallinarum phenotype VanC and four strains were E. casseliflavus
      phenotype VanC. PFGE was used to obtain 9 different restriction profiles of VRE
      strains. The analysis showed closer a similarity of E. casseliflavus strains (80
      95%) than between E. faecium strains (41%). CONCLUSIONS: The presence of VRE in a
      sample community of the Czech population was confirmed. It is clear that it is
      necessary to take into account the possibility of VRE spreading from the
      community into health care facilities.

PMID- 15744368
TI  - Use of EQUORAL in de novo renal transplant recipients.
AB  - This paper presents our experience to date with using a cyclosporine formulation
      Equoral (IVAX Pharmaceuticals) together with mycophenolate mofetil plus a steroid
      immunosuppressive regimen in the treatment of de novo renal transplant
      recipients. Ten cadaveric donor renal transplant recipients of mean age 51.6
      years (range 37-66) were followed up over 6 months for the development of
      rejection attacks and side effects. All patients received prednisolone,
      mycophenolate mofetil (1 g/day during the first 5 days posttransplant and then 20
      mg/kg/day) plus cyclosporine (3 mg/kg/day). Biopsy proven acute rejection
      episodes were observed in 2 out of 10 patients (20%). Six months patient as well
      as renal graft survival rate was 100%. The development of graft function was
      immediate after transplantation. The mean serum creatinine levels were gradually
      decreased. Over the 6-month posttransplant period, the function of the graft was
      satisfactory and stable. The majority of observed adverse events were those
      commonly reported with the use of cyclosporine and they resolved with a reduction
      in cyclosporine dose. Equoral treatment demonstrated an acceptable safety profile
      with maintenance of adequate renal function without incidence of
      malignancy/lymphoproliferative disease or serious infections. In conclusion,
      Equoral plus mycophenolate mofetil immunosuppression seems effective and safe on
      terms acute rejection rates, patient and renal graft survival rates and side
      profiles.

PMID- 15744369
TI  - Banding in aortic stent-graft fixation in EVAR.
AB  - The authors describe the method of surgical aortic banding for better stent-graft
      fixation in cases of problematic aortic neck in the endovascular infrarenal
      aneurysms repair.

PMID- 15744370
TI  - Iliac-renal bypass in EVAR of AAA with renal arteries arising from aneurysmal
      sac.
AB  - The authors describe treatment possibility for AAA with renal arteries arising
      from aneurysmal sac in high operating risk patients. They combined endovascular
      stent-grafting for aneurysmal sac exclusion and classical vascular surgical
      iliacrenal bypass for revascularisation of excluded renal arteries.

PMID- 15744371
TI  - AAA elective treatment indication tactics in EVAR era.
AB  - The authors describe their indication tactics for AAA elective treatment. Based
      on one-month morbidity and mortality they evaluate the results obtained in the
      past six years and compare the methods of open surgery, endovascular repair and
      combined strategy in AAAs elective repair.

PMID- 15744372
TI  - Eating disorders risk groups in the Czech Republic--cross-sectional epidemiologic
      pilot study.
AB  - OBJECTIVE: determination of risk groups for eating disorders in the population of
      young girls, primarily affiliated to certain sports or professional categories.
      METHOD: standardized Eating Attitude Test (EAT) questionnaire (40 questions) and
      general attitude questionnaire (43 other questions specific to eating disorders)
      were used. RESULTS: out of the total 403 persons questioned 11.7% had a score
      from EAT questionnaire > 29 points. These persons represent a potential risk
      population for the eventual development of eating disorder. Out of the total 403
      persons 10.9% had the Body Mass Index (BMI) lower or equal to 17.5. Out of these,
      only 5 individuals had the score > 29 because, especially at potential or initial
      stages, these two parameters do not have to necessarily correspond. Top gymnasts
      and figure skaters, followed by the models, dancers, ballet dancers and the
      cosmetic school students can be classified as having the highest degree of risk.
      DISCUSSION: assessment of the frequency of the condition which already shows
      signs of the beginning of a food intake disorder is important prerequisite for
      primary and secondary prevention of this disorder.

PMID- 15744373
TI  - Case report: restoration of edentulous mandible with 4 BOI implants in an
      immediate load procedure.
AB  - Dental implants for insertion from the lateral aspects of the jaw bone have been
      described repeatedly, since 1972. Long term results have been reported. Due to
      their design, BOI-Implants (basal osseointegration) can be installed even in
      those cases, where the vertical bone supply is reduced. This applies to the
      distal areas of the maxilla and the mandible. Furthermore, BOI-implants allow
      immediate loading as long as a balanced masticatory function can be achieved and
      maintained. This paper reports on the steps taken to install a full lower bridge
      in 4 BOI-implants and restoration in a patient with a circular bridge. The bridge
      was made from CoCr-Alloy and covered with acrylic resin. This treatment technique
      reduces costs and treatment time by about 50% compared to conventional
      techniques.

PMID- 15744374
TI  - Differentiation of CA1 cell elements in rat hippocampus ontogenesis.
AB  - Development of cell elements of CA1, their interaction in the process of cell
      differentiation during hippocampal band formation, developed CA1, and changes in
      the ageing process are discussed.

PMID- 15744375
TI  - An attempt to describe the ultrastructure and ultrahistochemistry of ciliary
      processes in mammals.
AB  - The aim of the present paper was to reexamine fine structural characteristics and
      glycogen topochemistry of ciliary processes in small laboratory mammals
      (hamsters, guinea-pigs and mice). A two-layered epithelium continuously covered
      all ciliary processes. The epithelium consisted of inner nonpigmented and outer
      pigmented cells whose apices faced each other. They were linked by desmosomes and
      tight junctions. Basal cell aspects showed extensively interdigitating processes
      adjacent to the inner (rarely also outer) basal lamina. The ciliary process core
      was made up of reticular fibers, few fibrocytes, and capillaries with or without
      fenestrations. No glycogen particles were found in the ciliary epithelium using
      the PA-TSC-SP procedure.

PMID- 15744376
TI  - Expression of p53, p63 and p73 in the orofacial region of human embryos.
AB  - We studied p53, p63, p73 protein expression in the orofacial region of five human
      embryos aged 7-18 weeks of intrauterine development using a three-step
      immunohistochemical method. Expression of proteins in various locations was
      evaluated semiquantitatively. A decrease in p53, p63 and p73 proteins occurred in
      the 13-week-old material with the exception of the tooth germ where a drop in p73
      appeared in the ninth week.

PMID- 15744377
TI  - The detection of myc proteins in the developing human kidney.
AB  - The aim of our work was the detection of c- and N- myc proteins in the developing
      kidney of human fetuses especially in the neogenous zone. These proteins being
      localized in nucleus and encoded by the cellular oncogene myc function as
      transcriptional factors. Myc gene represents the key control gene in the course
      of cellular proliferation and differentiation. It also participates in the
      regulation of apoptosis and the origin of some cancers. Both proteins have been
      proved to be inevitable for proper nephrogenesis in mice. Considering the dearth
      of studies dealing with human embryonic tissues, we attempted to map the
      localization and spatiotemporal relations of the expression of these proteins
      during human nephrogenesis. In addition, issuing from our previous observations,
      we tried to compare their ways of expression with those of Bcl-2 (antiapoptotic
      effect) and Bax (proapoptotic function) proteins. Histologically normal kidneys
      were collected from eight human fetuses ranging from the 10th-30th week of IUD.
      Tissue samples were fixed in methacarn and processed by routine paraffin
      technique. Standard indirect three-step immunohistochemical method was applied
      for the detection of N- and c-myc proteins. In the neogenous zone both proteins
      are markedly present in metanephrogenic blastema with declining intensity with
      the increasing age of fetus. Branches of ureteral bud are almost negative. Such
      localization is also typical for Bcl-2 protein whereas Bax positive cells are
      present mostly in branches of the ureteral bud. It is not clear if all these
      proteins collaborate in the course of regulation of apoptosis in human
      metanephros.

PMID- 15744378
TI  - Comparison of changes in AChE activity in the brain of the laboratory rat after
      soman and tabun intoxication.
AB  - The aim of this study was to compare changes in activity of acetylcholinesterase
      (AChE) in the brain and motor endplates of rat after administration of soman and
      tabun. We took brain and diaphragm from laboratory rats administered a median
      lethal dose (LD(50)) of soman or tabun. Enzyme activity of AChE was studied in
      selected structures of brain and in motor endplates in the diaphragm.
      Histochemical detection of AChE by Karnovski and Roots with simultaneous
      histochemical detection of alkaline phosphatase in case of brain sections was
      used. The highest activity of AChE in the control group was found in the
      striatum, amygdaloid nuclei, substantia nigra, superior colliculi, and motor
      nuclei of cranial nerves V, X a XII. LD(50) of both nerve agents dramatically
      decreased the activity of AChE in the structures studied--both brain and
      diaphragm. After intoxication by either agent, activity in above mentioned nuclei
      was characterized as low or focally moderate. Very low activity was seen in some
      structures (CA3 field of hippocampus, some nuclei of the tegmentum and cerebellar
      cortex). We found minimal differences in the histochemical picture of soman or
      tabun intoxication, apart from the striatum and the superior colliculi which
      showed stronger inhibition by tabun.

PMID- 15744379
TI  - Altered spermatogenesis in the hypodactylous rats.
AB  - Germinal epithelium of seminiferous tubules in adult, infertile hypodactylous
      males displays significant reduction in the number of germ-line cells. Detection
      of apoptosis in the germ-line cells during postnatal differentiation was
      performed to elucidate the mechanism of the decreased number of germ cells in the
      testes of adult rats. Evaluation of DNA fragmentation and expression of activated
      caspase-3 in germ cells did not confirm marked germ cell death during the onset
      of spermatogenesis as a main cause of significant reduction of germ cells in
      Hd/Hd testes of adult males. The primary cause of spermatogenesis defect seems to
      be rather associated with a disorder in the cell cycle regulation and
      interrelation of germ-line cells with Sertoli cells.

PMID- 15744380
TI  - Neural stem cells transplanted into intact brains as neurospheres form solid
      grafts composed of neurons, astrocytes and oligodendrocyte precursors.
AB  - Neural stem cells (NSCs) are tissue-specific stem cells with self-renewal
      potential that can give rise to neurons and glia in vivo and in vitro. The aim of
      this study was to transplant NSCs as whole neurospheres into intact brain and
      assess the fate and phenotype of their progeny generated in vivo. We isolated
      NSCs from E14 foetal rat forebrains and cultured them in basic fibroblast and
      epidermal growth factor-supplemented serum-free medium in the form of
      neurospheres in vitro. Neurospheres were transplanted into the intact brains of 2
      Wistar rats and after a period of 3 weeks, grafted brains were examined
      immunohistochemically. Neurospheres formed solid grafts that were found in the
      lateral ventricle and in the velum interpositum under the hippocampus. The
      majority of cells in the transplanted tissue were identified as beta-III
      tubulin(+), NeuN(+), PanNF(+) and synaptophysin(+) neurons and were accumulated
      throughout the graft centre. GFAP(+) astrocytes were scattered throughout the
      entire graft and astrocyte processes delimited the outer and perivascular
      surfaces. A great number of NG2(+) oligodendrocyte precursors was detected.
      Nestin(+) endothelial cells were found to line capillaries growing in the
      transplant. These data indicate that nestin(+) NSCs prevailing in neurospheres
      differentiate following transplantation into nestin(-) neuronal and glial cells
      which confirms the multipotency of NSCs. Three weeks posttransplantation neuronal
      and astrocyte cells reached terminal differentiation (formation of synaptic
      vesicles and superficial and perivascular limiting membranes) while elements of
      oligodendroglial cell lineage remained immature. Grafting stem cells as non
      dissociated neurospheres provide cells with favourable conditions which
      facilitate cell survival, proliferation and differentiation. However, in the
      intact brain, grafted neurosphere cells were not found to integrate with the
      brain parenchyma and formed a compact structure demarcated from its surroundings.

PMID- 15744381
TI  - Influence of amphotericin B deoxycholate or amphotericin B colloidal dispersion
      on renal tubule epithelium in rat.
AB  - Amphotericin B deoxycholate (AmB) or Amphotericin B colloidal dispersion (ABCD)
      are used in clinics for the treatment of systemic fungal infections. The goal of
      our study was to compare the nephrotoxicity of these drugs in rat kidney. The
      effects of AmB and ABCD on the ultrastructure of the epithelium of renal tubules
      were studied and evaluated using morphometric and statistical methods. Two groups
      of 3 animals were established: group 1 was treated with AmB desoxycholate and
      group 2, to which ABCD was applied. AmB caused more than ABCD ultrastructural
      changes in the cytoplasm of the epithelial cells: damage to mitochondria,
      vacuolation of cytoplasm, and increased values of volume density of peroxisomes.
      However, we failed to observe significant differences in morphology and density
      of the other cell organelles. The proximal tubules seemed to be more sensitive to
      the nephrotoxic influence of both formulas than the distal tubules of rat kidney.
      Although, AmB causes more severe damage than ABCD, both drugs cause damage to
      renal tubuli.

PMID- 15744382
TI  - Apoptosis and cell proliferation in chronic tonsillitis and oropharyngeal
      carcinoma: role of nitric oxide and cytokines.

PMID- 15744383
TI  - The occurrence of c-myc, p53 and Bcl-2 family proteins in the early phase of
      development of duodenal epithelium.
AB  - In last few years, numerous groups of proteins participating in the regulation of
      cell proliferation, differentiation and death during ontogenesis have been
      described. In this study we compared the occurrence of Bcl-2, p53 and myc protein
      families with the level of proliferative activity and apoptosis during
      development of duodenal epithelium. Paraffin embedded tissues of eight human
      embryos and foetuses aged from the 6th-18th week of IUD were used. For the
      detection of apoptotic cells the TUNEL method was performed, the proliferative
      marker PCNA and all the proteins studied were detected by means of indirect three
      step immunohistochemical method. In the 6th and 8th week of intrauterine
      development we observed isolated TUNEL positive epithelial cells only and this
      was accompanied by the disperse presence of PCNA as well as by all the studied
      proteins: Bcl-2, Bax, Bcl-XL, c-myc, N-myc, p53, p63 and p73. In the early foetal
      period of duodenal development we registered changes in PCNA and TUNEL positivity
      in accordance with the constitution of the stem cell pool on base of villi, where
      more numerous Bcl-2 positive cells were also found. The separation of primitive
      crypts and villi was not accompanied by any differences in distribution of Bax,
      Bcl-XL, c-myc, N-myc, p63 and p73 proteins between those compartments: all the
      studied proteins showed dispersed character. P53 rapidly decreased in this
      period. In the 18th week of intrauterine development the balance between
      proliferation in crypts and apoptosis of villi epithelium was well established
      and no p53 positive cells were found. In the presence of Bcl-2, Bax, Bcl-XL, p63
      and p73 we did not find any dramatic changes. The myc proteins were restricted
      within the epithelium of the Lieberkuhn crypts only.

PMID- 15744384
TI  - Possible regulatory mechanisms in the ovarian disorders.

PMID- 15744385
TI  - Plastination with silicone method S 10--monitoring and analysis causes of
      failure.
AB  - Plastination is in some cases unsuccessful. The goal of this work was to monitor,
      to describe and to analyse the reasons of S10 plastination method failure. We
      prepared the silicone-impregnated specimens using the standard silicone method S
      10. The causes of bad preparation are numerous. Usual defects produced during
      plastination process are the changes in the bulk, the changes in the colour and
      other visible defects (e.g. deformations, spots on the organs surface). The
      frequent reasons for these defects are: unsuitable temperature, using of old bad
      fixed formaldehyde specimens and too long gas-curing procedure. The knowledge of
      reasons of unsuccessful plastination is important condition for achievement the
      good results.

PMID- 15744386
TI  - Detection of beta-defensins and NOS in healthy and pathological nasal mucosa.

PMID- 15744387
TI  - Costal cartilages--a clue for determination of sex.
AB  - Mineralization and ossification in the human costal cartilages were studied
      radiologically. The aim of our study was to evaluate differences between males
      and females with respect to patterns of costal cartilage calcification and also
      with respect to ageing. Material for this study consists of 1044 chest and
      abdominal radiograms of the Czech population from the Department of Radiology
      (537 males and 507 females). Further radiograms of 18 chest plates were obtained
      at routine necropsy of cadavers. The radiograms were examined for pattern of
      ossification of the costal cartilage. The first rib cartilages were not
      considered because there are no sex differences. The lower ribs exhibit sexual
      dimorphism. Mineralization and ossification changes appear at the end of puberty
      and their occurrence increases with age. The sexual difference in pattern of
      human costal cartilages is statistically significant and thus highly predictive
      of sex determination.

PMID- 15744388
TI  - Production of H2O2 in human embryos after long-lasting cryopreservation and
      subsequent culture.
AB  - The production of hydrogen peroxide (H(2)O(2)) was investigated by means of
      cytochemical reaction with cerium chloride in human embryos cryostoraged for a
      long time period. The sites of H(2)O(2) generation were demonstrated at
      submicroscopic level in both freshly thawed embryos and in embryos and
      blastocysts formed after subsequent culture. The intact blastomeres as well as
      cells of well developed blastocysts did not produce any H(2)O(2). Two main
      intracellular sites of H(2)O(2) production were identified: mitochondria and
      plasma membranes. Some alterations and often destruction of plasma membrane
      integrity accompanied by massive H(2)O(2) generation are believed to be caused by
      the freezing and thawing.

PMID- 15744389
TI  - Surface morphology of kidney, ureters and urinary bladder models based on data
      from the visible human male.
AB  - The aim of the present work was to create a simplified high-resolution three
      dimensional model of kidneys, ureters and urinary bladder in a data form suitable
      for finite element/volume based numerical simulations. The exterior morphology of
      the organs was based on images from the Visible Human Male data set. In both the
      right and left kidney, there were defined their topographic relations to the
      neighbouring anatomical structures. This model of kidneys, ureters and urinary
      bladder will be incorporated into the model of The Visible Human Male abdomen and
      pelvis and it is ready to be used for numerical simulations in urinary system
      biomechanics.

PMID- 15744390
TI  - Rebuilding of rat intestinal mucous epithelium in prenatal ontogenesis.
AB  - Morphological differentiation of the intestinal epithelium in the laboratory rat
      occurs between the 16th and 21st day of prenatal development. The
      pseudostratified epithelium is rebuilt into simple epithelium of the future
      lining. A characteristic sign of this rebuilding is formation of primitive folds,
      villi and intraepithelial vacuoles corresponding in submicroscopic picture with a
      secondary luminization. On the tips of folds and villi groups of cells released
      from the epithelium are observed. In these cells expression of activated caspase
      3 confirms the presence of apoptosis in the process of cell death during
      epithelium rebuilding.

PMID- 15744391
TI  - Degradation phase of apoptosis during the early stages of human metanephros
      development.
AB  - Apoptosis as a vital process is necessary for human intrauterine development. Not
      only the induction and course of apoptosis, but engulfment of the apoptotic cells
      (bodies) were the centre of our interest. Macrophages were detected in the early
      stages of human intrauterine development and the role of macrophages in the
      clearance of apoptotic cells in the early stages of human metanephros development
      was confirmed.

PMID- 15744393
TI  - Delusional parasitosis: treatment with atypical antipsychotics.

PMID- 15744394
TI  - Asian tsunami: death-toll addiction and its downside.

PMID- 15744395
TI  - The challenge of private insurance for public good.

PMID- 15744396
TI  - Efforts under way to stem "brain drain" of doctors and nurses.

PMID- 15744397
TI  - How can health research help to save 500 000 mothers?

PMID- 15744398
TI  - Tsunami body count is not a ghoulish numbers game.

PMID- 15744400
TI  - Emergency doctor says WHO has key role in health crises.

PMID- 15744401
TI  - Socioeconomic differences in the burden of disease in Sweden.
AB  - OBJECTIVE: We sought to analyse how much of the total burden of disease in
      Sweden, measured in disability-adjusted life years (DALYs), is a result of
      inequalities in health between socioeconomic groups. We also sought to determine
      how this unequal burden is distributed across different disease groups and
      socioeconomic groups. METHODS: Our analysis used data from the Swedish Burden of
      Disease Study. We studied all Swedish men and women in three age groups (15-44,
      45-64, 65-84) and five major socioeconomic groups. The 18 disease and injury
      groups that contributed to 65% of the total burden of disease were analysed using
      attributable fractions and the slope index of inequality and the relative index
      of inequality. FINDINGS: About 30% of the burden of disease among women and 37%
      of the burden among men is a differential burden resulting from socioeconomic
      inequalities in health. A large part of this unequally distributed burden falls
      on unskilled manual workers. The largest contributors to inequalities in health
      for women are ischaemic heart disease, depression and neurosis, and stroke. For
      men, the largest contributors are ischaemic heart disease, alcohol addiction and
      self-inflicted injuries. CONCLUSION: This is the first study to use socioeconomic
      differences, measured by socioeconomic position, to assess the burden of disease
      using DALYs. We found that in Sweden one-third of the burden of the diseases we
      studied is unequally distributed. Studies of socioeconomic inequalities in the
      burden of disease that take both mortality and morbidity into account can help
      policy-makers understand the magnitude of inequalities in health for different
      disease groups.

PMID- 15744402
TI  - The global burden of disease attributable to low consumption of fruit and
      vegetables: implications for the global strategy on diet.
AB  - OBJECTIVE: We estimated the global burden of disease attributable to low
      consumption of fruit and vegetables, an increasingly recognized risk factor for
      cardiovascular disease and cancer, and compared its impact with that of other
      major risk factors for disease. METHODS: The burden of disease attributable to
      suboptimal intake of fruit and vegetables was estimated using information on
      fruit and vegetable consumption in the population, and on its association with
      six health outcomes (ischaemic heart disease, stroke, stomach, oesophageal,
      colorectal and lung cancer). Data from both sources were stratified by sex, age
      and by 14 geographical regions. FINDINGS: The total worldwide mortality currently
      attributable to inadequate consumption of fruit and vegetables is estimated to be
      up to 2.635 million deaths per year. Increasing individual fruit and vegetable
      consumption to up to 600 g per day (the baseline of choice) could reduce the
      total worldwide burden of disease by 1.8%, and reduce the burden of ischaemic
      heart disease and ischaemic stroke by 31% and 19% respectively. For stomach,
      oesophageal, lung and colorectal cancer, the potential reductions were 19%, 20%,
      12% and 2%, respectively. CONCLUSION: This study shows the potentially large
      impact that increasing fruit and vegetable intake could have in reducing many
      noncommunicable diseases. It highlights the need for much greater emphasis on
      dietary risk factors in public health policy in order to tackle the rise in
      noncommunicable diseases worldwide, and suggests that the proposed intersectoral
      WHO/FAO fruit and vegetable promotion initiative is a crucial component in any
      global diet strategy.

PMID- 15744403
TI  - Socioeconomic status overrides age and gender in determining health-seeking
      behaviour in rural Bangladesh.
AB  - OBJECTIVE: To study the health-seeking behaviour of elderly members (aged > 60
      years) of households in rural Bangladesh, to ascertain how their behaviour
      differs from that of younger people (aged 20-59 years) living in the same
      household and to explore the determinants of health-seeking behaviour. METHODS:
      Structured interviews were conducted to elicit information on the health-seeking
      behaviour of household members aged > 20 years. Respondents were asked about
      major illnesses occurring within 15 days prior to the interview. The sample
      consisted of 966 households that had at least one resident who was aged > 60 (32%
      of 3031 households). FINDINGS: We found no major differences in health-seeking
      behaviour between elderly people and younger adults. On average about 35%
      (405/1169) of those who reported having been ill during the previous 15 days in
      both age groups chose self-care/self-treatment; for both age groups the most
      commonly consulted type of provider was a paraprofessional such as a village
      doctor, a medical assistant or a community health worker. A household's poverty
      status emerged as a major determinant of health-seeking behaviour. The odds ratio
      (OR) that individuals from poor households would seek treatment from unqualified
      allopathic practitioners was 0.6 (95% confidence interval (CI) = 0.40-0.78); the
      odds ratio that individuals from poor households would seek treatment from
      qualified allopathic practitioners was 0.7 (95% CI = 0.60-0.95). For self-care or
      self-treatment it was 1.8 (95% CI = 1.43-2.36). Patients' level of education
      affected whether they avoided self-care/self-treatment and drugstore salespeople
      (who are usually unlicensed and untrained but who diagnose illnesses and sell
      medicine) and instead chose a formal allopathic practitioner (OR = 1.5; 95% CI =
      1.15-1.96). When a household's poverty status was controlled for, there were no
      differences in age or gender in terms of health-care expenditure. CONCLUSION: We
      found that socioeconomic indicators were the single most pervasive determinant of
      health-seeking behaviour among the study population, overriding age and sex, and
      in case of health-care expenditure, types of illness as well.

PMID- 15744404
TI  - The global distribution of risk factors by poverty level.
AB  - OBJECTIVE: To estimate the individual-level association of income poverty with
      being underweight, using tobacco, drinking alcohol, having access only to unsafe
      water and sanitation, being exposed to indoor air pollution and being obese.
      METHODS: Using survey data for as many countries as possible, we estimated the
      relative risk association between income or assets and risk factors at the
      individual level within 11 medium- and low-income subregions of WHO. WHO and The
      World Bank data on the prevalence of risk factors and income poverty (defined as
      living on < US$ 1.00 per day, US$ 1-2.00 per day and > US$ 2.00 per day) were
      analysed to impute the association between poverty and risk factors for each
      subregion. The possible effect of poverty reduction on the prevalence of risk
      factors was estimated using population-attributable risk percentages. FINDINGS:
      There were strong associations between poverty and malnutrition among children,
      having access only to unsafe water and sanitation, and being exposed to indoor
      air pollution within each subregion (relative risks were twofold to threefold
      greater for those living on < US$ 1.00 per day compared with those living on >
      US$ 2.00 per day). Associations between poverty and obesity, tobacco use and
      alcohol use varied across subregions. If everyone living on < US$ 2.00 per day
      had the risk factor profile of those living on > US$ 2.00 per day, 51% of
      exposures to unimproved water and sanitation could be avoided as could 37% of
      malnutrition among children and 38% of exposure to indoor air pollution. The more
      realistic, but still challenging, Millennium Development Goal of halving the
      number of people living on < US$ 1.00 per day would achieve much smaller
      reductions. CONCLUSION: To achieve large gains in global health requires both
      poverty eradication and public health action. The methods used in this study may
      be useful for monitoring pro-equity progress towards Millennium Development
      Goals.

PMID- 15744405
TI  - Private health insurance: implications for developing countries.
AB  - Private health insurance is playing an increasing role in both high- and low
      income countries, yet is poorly understood by researchers and policy-makers. This
      paper shows that the distinction between private and public health insurance is
      often exaggerated since well regulated private insurance markets share many
      features with public insurance systems. It notes that private health insurance
      preceded many modern social insurance systems in western Europe, allowing these
      countries to develop the mechanisms, institutions and capacities that
      subsequently made it possible to provide universal access to health care. We also
      review international experiences with private insurance, demonstrating that its
      role is not restricted to any particular region or level of national income. The
      seven countries that finance more than 20% of their health care via private
      health insurance are Brazil, Chile, Namibia, South Africa, the United States,
      Uruguay and Zimbabwe. In each case, private health insurance provides primary
      financial protection for workers and their families while public health-care
      funds are targeted to programmes covering poor and vulnerable populations. We
      make recommendations for policy in developing countries, arguing that private
      health insurance cannot be ignored. Instead, it can be harnessed to serve the
      public interest if governments implement effective regulations and focus public
      funds on programmes for those who are poor and vulnerable. It can also be used as
      a transitional form of health insurance to develop experience with insurance
      institutions while the public sector increases its own capacity to manage and
      finance health-care coverage.

PMID- 15744406
TI  - Prevention and treatment of human immunodeficiency virus/acquired
      immunodeficiency syndrome in resource-limited settings.
AB  - Strategies for confronting the epidemic of human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) have included a range of different
      approaches that focus on prevention and treatment. However, debate persists over
      what levels of emphasis are appropriate for the different components of the
      global response. This paper presents an overview of this debate and briefly
      summarizes the evidence on a range of interventions designed to prevent the
      spread of HIV infection, paying particular attention to voluntary counselling and
      testing, treatment for sexually transmitted infections and prevention of mother
      to-child transmission. We also review the experience with antiretroviral therapy
      to date in terms of response rates and survival rates, adherence, drug
      resistance, behavioural change and epidemiological impact. Although various
      studies have identified strategies with proven effectiveness in reducing the
      risks of HIV infection and AIDS mortality, considerable uncertainties remain.
      Successful integration of treatment and prevention of HIV/AIDS will require a
      balanced approach and rigorous monitoring of the impact of programmes in terms of
      both individual and population outcomes.

PMID- 15744407
TI  - When truth is unwelcome: the first reports on smoking and lung cancer.

PMID- 15744409
TI  - Improving the world's health through national public health institutes.

PMID- 15744408
TI  - Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma.

PMID- 15744410
TI  - Missing deaths from pesticide self-poisoning at the IFCS Forum IV.

PMID- 15744411
TI  - Polio eradication: end-stage challenges.

PMID- 15744413
TI  - A new occurrence of Limnoperna fortunei (Dunker 1856) (Bivalvia, Mytilidae) in
      the State of Sao Paulo, Brazil.
AB  - The freshwater mussel Limnoperna fortunei (Dunker 1856) (Bivalvia, Mytilidae) has
      been found in the Parana river, near Rosana, Sao Paulo. This is the first record
      of this specie in Sao Paulo State. This population of Limnoperna fortunei seems
      to be young and in a colonization process.

PMID- 15744414
TI  - Diversity assessment of benthic macroinvertebrates, yeasts, and microbiological
      indicators along a longitudinal gradient in Serra do Cipo, Brazil.
AB  - The main goals of this study were: 1) to evaluate the structure, diversity, and
      functional trophic group composition of benthic macroinvertebrate communities; 2)
      to characterize water quality in the headwaters of the Doce river watershed,
      based on physical, chemical, and biological parameters (benthic
      macroinvertebrates, fecal coliforms, heterotrophic bacteria, and yeasts); and 3)
      to contribute to the knowledge of the structure and function of longitudinal
      gradients in lotic ecosystems in Brazil. A total of 60 benthic macroinvertebrate
      taxa were identified, the dominant group being the aquatic insects, with 50
      families distributed in 8 orders. The dry period presented higher values of
      taxonomic richness and total density of benthic macroinvertebrates. A decreasing
      gradient was observed in these variable values from the 3rd order stretch down to
      the 6th order stretch. The highest Shannon-Wiener diversity values were found in
      the rainy period in the 3rd order stretches, which presented well-developed
      riparian forest. Besides the 3rd order stretches, the Pielou evenness index
      values were also high in the 6th order stretch. The collectors, together with the
      scrapers, predominated in the benthic macroinvertebrate communities in all river
      stretches, except in the 2nd, 4th, and 5th order stretches in the rainy period,
      where communities were dominated by filterers. The shredders and predators
      presented low densities for all river stretches. All microbiological variables
      presented low levels. Due to the high counts of heterotrophic bacteria and
      coliforms, the studied river stretches presented inadequate potability but
      adequate balneability levels. The results suggest that the structure, diversity,
      and composition of the benthic macroinvertebrate communities are influenced by
      the trophic resource availability, seasonality, and sediment heterogeneity. The
      microbiological results of this study allow inferring that the waters from Serra
      do Cipo have excellent potential for recreational use and as future sources of
      water for human consumption.

PMID- 15744416
TI  - Two new species of Fannia Robineau-Desvoidy (Diptera, Fanniidae).
AB  - Fannia Robineau-Desvoidy is known from 63 neotropical species, 24 of them with
      occurence in Rio de Janeiro State. Two new species from Rio de Janeiro State are
      added to the genus: F. tibialis, sp. n and F. unica, sp. n. Male specimens of
      both are described. Morphological characters and terminalia are illustrated. Each
      species is briefly discussed.

PMID- 15744415
TI  - Ichthyofauna of two streams (silted and reference) in the Upper Parana river
      basin, Southeastern Brazil.
AB  - In this study the fish assemblages of the silted Aguas Claras stream (AC) was
      compared with that of a reference, the Sao Carlos stream (SC), so as to identify
      potential fish indicators of integrity or degradation. Both streams, located
      about 5 km from one another, are part of the Upper Parana river basin, Brazil,
      and present similar physiographical features. Twenty-one species were collected
      in AC (1,271 specimens) and 18 in SC (940 specimens). In AC, dominant species
      e.g., Corydoras aeneus (sandy pools), Serrapinnus notomelas, and Pyrrhulina
      australis (warm marginal shallow pools) were those favored by new microhabitats
      linked to siltation and removal of the riparian vegetation. Changes in the
      composition of the marginal vegetation resulted in dominance of species such as
      Hisonotus francirochai (marginal grasses). In SC the dominant species was
      Phalloceros caudimacultus, abundant in marginal shallow pools, and Trichomycterus
      diabolus. and Hypostomus nigromaculatus, exclusively riffle-dwelling species,
      which were absent in AC. Fish assemblage monitoring is recommended for use in
      riparian management programs in order to evaluate negative instream sedimentation
      effects.

PMID- 15744417
TI  - A new Notoschoenomyza Malloch and a key to the species (Diptera, Muscidae,
      Coenosiinae).
AB  - A new species of Notoschoenomyza Malloch, N. diminuta sp. nov. from Chile, is
      described and the male and female terminalia are illustrated. A key to the
      identification of all Notoschoenomyza species is presented.

PMID- 15744418
TI  - Sintopy of two Tropidurus lizard species (Squamata: Tropiduridae) in a rocky
      Cerrado habitat in central Brazil.
AB  - We studied the ecology of Tropidurus itambere and T. oreadicus that occur
      syntopically in rocky habitats of Cerrado vegetation in central Brazil during the
      dry season (April to September 2000). The two species are ecologically similar,
      but somewhat differentiated in vertical microhabitat use. The two species
      preferred rocky surface microhabitat. Both species demonstrated a unimodal
      activity pattern, with a peak between 10 and 15 h. Their diets were similar in
      composition and prey size. The most frequent item used by both species was ants,
      whereas the most important preys volumetrically were termites and ants. Small
      morphological differences observed between the two Tropidurus species could
      explain minor microhabitat divergence: T. itambere is slightly smaller, heavier,
      and more robust, and uses lower perches. T. oreadicus is larger, lankier, with
      longer extremities (tail, fore- and hindlegs), and uses a larger vertical
      microhabitat range. These ecological differences are slight, when compared with
      those observed between sympatric species of Tropidurus in spatially more
      heterogeneous landscapes. Considering the slight ecomorphological divergence
      between the two Tropidurus species and their high abundance in outcrops, we
      suggest that interspecific territoriality is the mechanism of coexistence.

PMID- 15744419
TI  - Feeding of introduced species of Cichla (Perciformes, Cichlidae) in Volta Grande
      reservoir, River Grande (MG/SP).
AB  - Both species studied, Cichla cf. ocellaris and Cichla monoculus, fed mainly on
      fish, the first on Cichla spp., Plagioscion squamosissimus, and Tilapia rendalli,
      and the second, Cichla monoculus, on Cichla spp. Both diets indicated a strong
      correlation among the food items. Remarkable ontogenetic change was noted in both
      species diet: the young fed on crustaceans and insects while the adults fed
      mainly on fishes. The species studied, which are highly adapted to a brief life
      span, cause serious damage to the fish communities by predation, competition, and
      cascade effects throughout the whole trophic chain.

PMID- 15744420
TI  - Acute morphological and physiological effects of lead in the neotropical fish
      Prochilodus lineatus.
AB  - The present study investigated lead effects on gill morphology, hematocrit, blood
      sodium, glucose, lipids, protein, and cholesterol of Prochilodus lineatus exposed
      to two sublethal lead concentrations for 96 h. Preliminary series of short-term
      static toxicity tests were run to determine LC50 (96 h) of lead in P. lineatus,
      which was 95 mg Pb.L-1. Therefore, lead concentrations tested in the sublethal
      experiments were 24 and 71 mg Pb.L-1, which correspond to 25% and 75% of the LC50
      (96 h), respectively. Gills of P. lineatus exposed to both lead concentrations
      during 96 h presented a higher occurrence of histopathological lesions such as
      epithelial lifting, hyperplasia, and lamellar aneurism. P. lineatus did not show
      significant alterations in hematocrit during exposure to both lead
      concentrations. Fish exposed to the highest lead concentration showed a
      significant decrease in Na+ plasma concentration after 48 h, possibly reflecting
      a sodium influx rate decrease. P. lineatus exposed to both lead concentrations
      presented a "classical general adaptation syndrome to stress", as hyperglycemia
      associated with lowered lipids and proteins was reported. Stress-response
      magnitude was dose-dependent. While the response to the lowest lead concentration
      might represent adaptation, the highest concentration seems to characterize
      exhaustion.

PMID- 15744421
TI  - Diet and trophic groups of an aquatic insect community in a tropical stream.
AB  - The diet and trophic groups of an assemblage of aquatic insects were studied in a
      tropical stream. Genera of the orders Ephemeroptera, Odonata, Plecoptera,
      Lepidoptera, and Hemiptera showed feeding specialization. Others, such as
      Trichoptera, Coleoptera, and Diptera, showed great diet variation with genera of
      different trophic groups. Seasonal variation of insect diet, evident only for
      some genera of the orders Trichoptera, Lepidoptera, Coleoptera, and Diptera, was
      due to the differences observed in community composition and to generalist habits
      of these genera. However, the seasonal comparison of trophic groups showed no
      significant statistical differences. The great importance of organic matter, a
      non-limited resource, in the diet of Ribeirao do Atalho aquatic insects may be
      the explanation for the trophic stability in this community organization.

PMID- 15744422
TI  - Effects of algicide (copper sulfate) application on short-term fluctuations of
      phytoplankton in Lake Paranoa, central Brazil.
AB  - Short-term fluctuations and structure of phytoplankton were examined for two
      months in the dry season (August-September/1997) in a eutrophic reservoir of
      central Brazil. Algicide treatment for the control of Microcystis aeruginosa
      bloom influenced the short-term variation pattern of the phytoplankton community.
      Algicide treatment was effective in controlling M. aeruginosa bloom, but it also
      influenced the Cylindrospermopsis raciborskii population. These species retained
      low densities, showing small colonies and trichomes, respectively. Drops in
      Cyanobacteria populations following algicide treatment were succeeded by
      progressive increase in Chlorophyta. The shifts in environmental conditions may
      have allowed the development of this group. In this study correspondence analysis
      of abundance data for phytoplankton assemblage in lake Paranoa revealed that
      available light, rather than chlorophyll-a, total suspended material, and water
      temperature, accounted for most of the short-term fluctuation in phytoplankton
      structure during algicide application. Canonical correspondence analysis (CCA)
      showed the primary importance of water transparency changes in abundance of taxa
      in the community. Algicide treatment for the control of nuisance blooms is
      discussed as a contribution to improved efficiency in reservoir management.

PMID- 15744423
TI  - Electroantennography in the study of two stingless bee species (Hymenoptera:
      Meliponini).
AB  - The first recorded electroantennographic preliminary studies on stingless bees
      have been performed using two species of Frieseomelitta from Brazil. Experiments
      with F. silvestrii and F. varia showed that antennae respond to hexane extracts
      of heads and abdomens of both species and posterior tibia of F. silvestrii (which
      carry plant resin), as well as to the pure compounds 2-heptanol and 2-nonanol,
      which occur in the mandibular glands of both species, and to the terpenes alpha
      cubebene, humulene, and beta-caryophyllene found on their tibia and in the
      cerumen of their nests.

PMID- 15744424
TI  - Age and growth of the porthole shovelnose catfish (Hemisorubim platyrhynchos) in
      the Pantanal.
AB  - The porthole shovelnose catfish, Hemisorubim platyrhynchos, is the sixth largest
      pimelodidae of the Pantanal. Its age and growth were studied using pectoral fin
      spines from fish collected in the Cuiaba river basin, Pantanal. The fish, which
      came from commercial and experimental fisheries, were all caught with hook and
      line. Growth-ring formation time could not be defined through the Kruskal-Wallis
      test on marginal increment (H = 4.142; p = 0.247). Nevertheless, decrease in the
      marginal increment index occurring as waters recede suggests this as the probable
      time when growth rings form. Estimation of the parameters of von Bertalanffy
      growth curve, adjusted through nonlinear regression to observed fork lengths,
      with L(infinity) fixed at 64 cm, were: k = 0.222 year(-1); t(o) = -2.149 years.
      Individual life span was estimated at 11.4 years. The results suggest that fork
      length is a good predictor of age for individuals of this species.

PMID- 15744425
TI  - Empirical diversity indices applied to forest communities in different
      successional stages.
AB  - In this paper we examine the precision of six diversity indices, four of them
      empirical when including in their formulae climax adaptation numbers. These
      numbers define the succession position of the plant species in five forest areas
      in Sao Paulo State. We simulated hypothetical forests and compared the results
      with a list of species in the five areas. Low agreement was found among the
      indices in succession stages. Including the climax adaptation numbers increased
      precision for only some indices.

PMID- 15744426
TI  - Localization of acid phosphatase activity in the testis of two teleostean species
      (Oreochromis niloticus and Odonthestes perugiae).
AB  - Acid phosphatase (AcP) activity was investigated in the testes of two species of
      teleosts in two seasons: summer and winter. AcP activity was detected in Sertoli
      cells from tilapia (Oreochromis niloticus) only during the nonreproductive period
      of its annual cycle, corresponding to the winter months. In kingfish (Odonthestes
      perugiae), the enzymatic reaction was identified during the non-reproductive
      period (summer) in epithelial cells of the efferent ducts but not in Sertoli
      cells. These data suggest that the enzyme is involved in the absorption of
      residual spermatid cytoplasm and as well as in the removal of spermatozoa
      remaining after the reproductive period. In kingfish, this heterophagous function
      is carried out by the efferent duct cells and not by Sertoli cells.

PMID- 15744427
TI  - Flooded native pastures of the northern region of the Pantanal of Mato Grosso:
      biomass and primary productivity variations.
AB  - The Pantanal comprises a number of landscape units, submitted to a flood pulse
      with variable intensity or regularity. One of these units, the flooded plains, is
      important in cattle raising. This study was carried out in the northern portion
      of the Pantanal and presents data related to the productive dynamics of the
      flooded native pastures both protected from and exposed to cattle. The greatest
      total biomass values were for the protected pasture due to accumulated dead
      biomass. Net primary production presented smaller values at the flood-season
      start and increasing gradually beginning in the subsequent rainy season. However,
      consumption by cattle was also more intense during the months of greater
      precipitation. The effect of cattle in pastures is of fundamental importance to
      management since it prevents the dead biomass excess that increases fire risks.

PMID- 15744428
TI  - Flowers, fruits, and the abundance of the yellow-chevroned parakeet (Brotogeris
      chiriri) at a gallery forest in the South Pantanal (Brazil).
AB  - Parakeets usually forage for massive and ephemeral plant resources at forest
      canopies. Fruit pulp is widely cited as a major food resource for these birds,
      which often eat seeds and nectar. In this study, I assessed flower and fruit
      production at a gallery forest in the Pantanal flood plain (Brazil) in order to
      evaluate the relationship between food resource production and abundance of a
      common parakeet, Brotogeris chiriri. Also, I evaluated the relationship between
      food resource production and foraging activity. Parakeet abundance varied
      markedly along the year, coinciding with massive episodes of flower and fleshy
      fruit availability. Inga vera nectar, intensely used during the latter part of
      dry season, was by far the most exploited food item by parakeets when they were
      very abundant. The nectar comprised 34% of the parakeets' diet (N = 131 feeding
      records) at the gallery forest, while fleshy fruits made up the rest. Parakeets
      principally exploited fruits of Cecropia pachystachya and Ficus luschnathiana,
      besides palm fruits and Inga vera arils. The consistent relationship between
      foraging activity and parakeet abundance, as well as the coincidence between
      fluctuations of these parameters and availability of major food resources,
      suggests that food availability mostly influenced B. chiriri occurrence in the
      gallery forest. Furthermore, I found no evidence for gallery forest use for
      roosting and/or breeding, in spite of the fact that such factors usually
      influence local parakeet abundance.

PMID- 15744429
TI  - Relative efficiency of anuran sampling methods in a restinga habitat (Jurubatiba,
      Rio de Janeiro, Brazil).
AB  - Studies on anurans in restinga habitats are few and, as a result, there is little
      information on which methods are more efficient for sampling them in this
      environment. Ten methods are usually used for sampling anuran communities in
      tropical and sub-tropical areas. In this study we evaluate which methods are more
      appropriate for this purpose in the restinga environment of Parque Nacional da
      Restinga de Jurubatiba. We analyzed six methods among those usually used for
      anuran samplings. For each method, we recorded the total amount of time spent (in
      min.), the number of researchers involved, and the number of species captured. We
      calculated a capture efficiency index (time necessary for a researcher to capture
      an individual frog) in order to make comparable the data obtained. Of the methods
      analyzed, the species inventory (9.7 min/searcher /ind.- MSI; richness = 6;
      abundance = 23) and the breeding site survey (9.5 MSI; richness = 4; abundance =
      22) were the most efficient. The visual encounter inventory (45.0 MSI) and patch
      sampling (65.0 MSI) methods were of comparatively lower efficiency restinga,
      whereas the plot sampling and the pit-fall traps with drift-fence methods
      resulted in no frog capture. We conclude that there is a considerable difference
      in efficiency of methods used in the restinga environment and that the complete
      species inventory method is highly efficient for sampling frogs in the restinga
      studied and may be so in other restinga environments. Methods that are usually
      efficient in forested areas seem to be of little value in open restinga habitats.

PMID- 15744430
TI  - Loss of heterozygosity by mitotic recombination in diploid strain of Aspergillus
      nidulans in response to castor oil plant detergent.
AB  - Somatic recombination in heterozygous diploid cells may be a promotional agent of
      neoplasms by inducing homozygosity of defective genes. Tumor suppressor genes may
      in this way be completely suppressed in recombinant cells. In this work, the
      genotoxic effects of detergent derived from the castor oil plant (Ricinus
      communis) in heterozygous diploid cells of Aspergillus nidulans are evaluated.
      Previous studies have evaluated the application of this substance in endodontic
      treatments as an irrigating solution. The recombinogenic potential of the
      compound has been studied through the production of homozygous cells for
      nutritional markers riboA1, pabaA124, biA1, methA17, and pyroA4. Detergent was
      diluted to 1:10, 1:20, and 1:40, and morphologic alterations, delay in
      conidiophore development, and mitotic recombination occurrence were reported for
      the three dilutions. Although past studies have demonstrated the antimicrobial
      action of the detergent under analysis, our results revealed its cytotoxic
      effects and recombinogenic potential.

PMID- 15744431
TI  - Embryonic development time of Penilia avirostris Dana, 1852 in a tropical bay in
      Brazil.
AB  - Development time of embryos in the brood pouch of the cladoceran Penilia
      avirostris Dana, 1852, was estimated by collecting zooplankton daily for 15 days
      in surface water of Guanabara Bay, Brazil. Each day the maturity stage of embryos
      of 90 parthenogenic females was noted. Total development time (egg to birth)
      varied from 2 to 3 days, the immature phase (stages I to IV) being generally
      longer (2 days) than intermediate and mature phases (1 day, stages V to XII).
      Similar results were obtained from Bottrell's equation, which takes water
      temperature into account.

PMID- 15744432
TI  - Differential trappability of small mammals in three habitats of Southeastern
      Brazil.
AB  - We compared the trappability of marked and unmarked individuals in species of
      marsupials and rodents of three tropical assemblages of small mammals in Brazil.
      Two studies used trapping grids, one in cerrado and the other in an Atlantic
      forest reserve, whereas the study in a rural area used transects. In the two
      studies using trapping grids, marked animals were frequently more trappable than
      unmarked ones, but in some species this difference was not significant. In the
      rural area, marked and unmarked animals did not differ significantly. The number
      of recaptures per resident animal was higher in the two studies using trapping
      grids than in the rural area where transects were used. Differences in
      trappability between the three studies might have been caused by differences not
      only in trapping design (grids vs. transects), but also in the type of trap used,
      bait, and habitat. Although differential trappability tends to be considered the
      rule in small mammals, these results suggest that trappability of marked and
      unmarked animals may be specific for the particular combination of sampling
      design, field methods, and habitat under study.

PMID- 15744434
TI  - A method for preparing remains of Cladocera (Crustacea) and Chironomid (Diptera:
      Insecta) for scanning electron microscopy.

PMID- 15744435
TI  - Changes in growth seasonality throughout Netuma barba (Lacepede, 1803)
      (Siluriformes, Ariidae) Ontogeny.

PMID- 15744433
TI  - Birds of a habitat spectrum in the Itirapina Savanna, Sao Paulo, Brazil (1982
      2003).
AB  - Some 231 birds were recorded on a sandy plateau in central Sao Paulo, in an area
      forming a natural "habitat spectrum", from dry or wet grasslands to bushy ones
      (campo-cerrado) plus gallery scrub, marshes, and low woods. Subtracting 12
      species that mostly flew over, and 56 species that seemed to be vagrants or
      accidental visitors, 163 species were regular (including 14 that center in nearby
      anthropogenically-modified zones). The 69 in gallery areas are mostly regionally
      common woodland species, but one southeastern species has disappeared over the
      years and three northwestern dry-forest species have entered. The 81 grassland
      species include several rare birds, and hence are important despite exhibiting
      lower biodiversity than in regional forest areas. Seven rare species disappeared
      over the years, some due to lack of fires, others because of either recent
      "greenhouse" dry years or protected vegetation growing to taller campo-cerrado.
      Several other species are becoming rare. Low vegetation forms a spectrum of
      temporally unstable habitats that change rapidly; one needs actively managed
      large areas and corridors even though many open-area birds can fly long distances
      to varying habitat patches.

PMID- 15744436
TI  - Scale-bearing chrysophytes from the State of Sao Paulo, Brazil, 2: additions to
      the flora.

PMID- 15744437
TI  - Characterization of the lipid composition at the proximal root regions of human
      hair.
AB  - The hair lipid composition collected from 44 Japanese females between 1 and 81
      years of age was examined for eight lipids including hydrocarbons (HCs), squalene
      (SQ), wax esters (WEs), triglycerides (TGs), fatty acids (FAs), cholesterol (CH),
      ceramides (CERs), and 18-methyl eicosanoic acid (MEA). In this study, the 5-cm
      length from the proximal root end of hair fibers, which had never been exposed to
      any chemical treatment, was used after 5-min incubation with hexane following
      shampooing. Hair lipids were extracted with solvent and subsequent alkali-solvent
      and were then analyzed by a combination of chromatography. Although the average
      contents of the lipids showed great fluctuations among individuals, there were
      significant correlations between the levels of each lipid, which allowed for the
      classification of the hair lipids into four groups: group A: SQ, WEs, TGs, and
      FAs (designated as endogenous lipids based upon their sebum origin); group B: CH
      and CERs (designated as endogenous lipids); group C: HC (unknown origin); and
      group D: MEA (the other endogenous lipid). A principal component analysis for
      eight lipids revealed that the hair lipid composition was characterized by a
      predominant negative correlation between each lipid for groups A and B. This
      negative correlation suggests that the endogenous lipids in group B serve as a
      barrier against the penetration of predominantly sebum-derived exogenous lipids
      (group A). Endogenous lipids consisting of CH and CERs (group B) and MEA (group
      D) should be designated as intrinsic internal lipids of human hair.

PMID- 15744439
TI  - A novel "permanent" acid-type hair color made possible with dye-metal ion complex
      technology.
AB  - The advantages and disadvantages of oxidative permanent and acid-type semi
      permanent hair colors are evident. The former provides a longlasting "permanent"
      color, while the latter imparts less damage to the hair. We developed a novel
      acid-type hair color technology that can allow an acid dye and a metal ion to
      form a complex inside the hair similar to the oxidative hair color. It is well
      known that acid dye diffuses into the hair and creates an ionic bond with the
      positively charged amino acid residues of hair protein. However, the dye can be
      extracted easily from the hair by daily shampooing due to the weakness of the
      bond. In order to strengthen this bond and to prevent the extraction of the dye
      by shampooing, an aluminum chloride ion was chosen as the metal ion component to
      form the dye-metal complex. A proper composition of penetration enhancers, benzyl
      alcohol and ethyl alcohol, was required to allow acid dyes to interact with the
      aluminum chloride ion after each component penetrates deeply into the hair to
      form a complex inside the hair. To provide color brightness and a color longevity
      effect to hair color, glycolic acid was also selected due to the observation that
      a weak acid with a small molecular weight would enhance those effects.

PMID- 15744438
TI  - L-Ergothioneine scavenges superoxide and singlet oxygen and suppresses TNF-alpha
      and MMP-1 expression in UV-irradiated human dermal fibroblasts.
AB  - Ergothioneine (EGT) is a sulfur-containing amino acid, and is presumed to
      function as a natural antioxidant. The purpose of this study was to identify the
      nature of the antioxidant activity and investigate the effects of EGT on UV
      induced cellular response. In chemical studies, EGT scavenged the superoxide
      anion radical (*O(2)(-)) and singlet oxygen ((1)O(2)). In cultured fibroblasts,
      EGT suppressed TNF-alpha up-regulation by UVB irradiation. In addition, in
      fibroblasts exposed to UV-A, EGT suppressed the expression of matrix
      metalloproteinase 1 (MMP-1) protein by nearly 50% and reduced MMP-1 mRNA
      expression. From these results, we conclude that EGT scavenges reactive oxygen
      species generated by both Type I and Type II photosensitization and suppresses
      both TNF-alpha expression and MMP-1 at their transcriptional level. EGT may
      reduce skin anti-aging effects after UV irradiation by the scavenging of *O(2)(-)
      and (1)O(2), and reducing signals for protease and inflammatory activity.

PMID- 15744440
TI  - A study of the photolightening mechanism of red hair with visible and ultraviolet
      light: comparison with blond hair.
AB  - The photolightening behavior of red hair was investigated. Red hair was found to
      lighten to a similar extent by irradiation from both ultraviolet (UV) and visible
      (VIS) light. Under the same irradiating conditions, blond hair was lightened by
      VIS light but did not lighten by UV light until it was washed after irradiation
      (1). These different photolightening behaviors of red and blond hair are supposed
      to be due to differences in their melanin compositions. The dominant type of
      melanin in red hair is pheomelanin; while blond hair investigated in the previous
      work contained both eumelanin and pheomelanin, with mainly eumelanin (2).
      Consequently, in this investigation, the photolightening behaviors of red and
      blond hair were compared to clarify the differences in photosensitivity between
      the two types of melanin.

PMID- 15744444
TI  - Electron spectroscopy and microscopy applied to chemical and structural analysis
      of hair.
AB  - The application of surface specific x-ray photoelectron spectroscopy (XPS) and
      scanning electron microscopy (SEM) will be shown to be an effective means for the
      elucidation of hair fiber surface chemistry and structure. Example studies of
      bleaching and fiber conditioning treatments are discussed. The bleached fiber
      surface is found to become more hydrophilic due to the loss of the naturally
      occurring hydrocarbon overlayer and oxidation of surface functional groups as a
      result of bleaching. Comparison between generic bleaching regimens illustrates
      the importance of increased pH and the presence of surfactant for effective
      treatment. Adsorption of conditioning diester quat and dimethicone molecules
      reintroduces a hydrophobic like surface layer on the hair fiber. Spectroscopic
      data indicated a segregated adsorption structure of the chemically different
      conditioning molecules. Electron microscope images of the conditioned hair shows
      a smooth uniform surface.

PMID- 15744446
TI  - [Forearm fractures in children].
AB  - Fractures of the forearm in children are quite frequent injuries, treated in
      emergency rooms. Most of them occur during leisure or sport activities. Most
      cases are monotraumatic. The diagnosis can be made by a conventional x-ray
      examination of the forearm in two planes. It is possible to differentiate between
      stable fractures (greenstick fractures) and unstable (dislocated) fractures. The
      first-line therapy for stable fractures or fractures which can be reduced
      anatomically correctly, is the conservative procedure using a long arm cast.
      Axial dislocation up to 20 degrees (age <5 years) or up to 10 degrees (age >5
      years) can be accepted. Special cases, such as Monteggia or Galeazzi fractures,
      must be considered. Unstable fractures have to be reduced during surgical stand
      by. The state of the art in surgical therapy is intramedullary nailing with
      titanium elastic nails. Open fractures and fractures with severe soft tissue
      injuries can be treated with external fixation. Osteosynthesis with plates should
      only be used for special indications. By following therapeutic principles, a
      successful outcome can be achieved and later complications are rare.

PMID- 15744445
TI  - [Strategies for perioperative sympatho-modulation].
AB  - Despite the growing evidence for the efficacy of different sympatho-modulatory
      therapies to lower perioperative cardiac morbidity and mortality, such
      therapeutic strategies are rather infrequently used in daily clinical practice.
      Most physicians involved in perioperative medicine are aware of the increasing
      literature related to this topic, but only few comply with current clinical
      practice guidelines even in the absence of contraindications. This review
      discusses possible explanations for this reluctance and again summarizes the
      basic and clinical principles of current sympatho-modulatory therapies including
      alpha(2)-agonism, beta-adrenergic antagonism, and regional anesthetic techniques
      in modern anesthetic practice. In addition, the emerging perioperative concept of
      a patient-tailored individualized pharmacotherapy based on "gene profiling",
      particularly the adrenergic polymorphisms, is discussed.

PMID- 15744447
TI  - Piriform and trochanteric fossae. A drawing mismatch or a terminology error? A
      review.
AB  - The current literature indicates that the standard starting point for
      intramedullary nailing is the piriform fossa. The accuracy of the entry point for
      anterograde femoral intramedullary nailing between published texts and relevant
      illustrations was recorded. The piriform fossa is the site of insertion of the
      piriform tendon and represents a small, shallow depression located on the tip of
      the greater trochanter. The trochanteric fossa is a deep depression on the inner
      surface of the greater trochanter, and in the vast majority of the published data
      is indicated incorrectly as "piriform fossa". As a result of either a recurrent
      drawing mismatch or a terminology error, the correct entry point for anterograde
      femoral intramedullary nailing is confusing and should be indicated in the
      current literature. The trochanteric fossa appears to be the standard entry point
      that most surgeons recommend.

PMID- 15744448
TI  - Neurovascular relationships of the approaches for arthroscopic total
      trapeziectomy with ligamentous stabilization.
AB  - The aim of this study was to define the neurovascular relationships of the
      approaches used during arthroscopic total trapeziectomy with the Thompson
      "suspension-plasty." Fifteen fresh cadavers in which trapezio-metacarpal
      arthritis had been confirmed by preoperative radiographs were chosen. There were
      12 women and 3 men (average age: 87 years), and small joint arthroscopy equipment
      was used. Two approaches for the trapezio-metacarpal joint were used: an ulnar
      approach situated at the ulnar border of the extensor pollicis brevis tendon and
      a radial approach placed at the middle of a line joining the tendons of the
      flexor carpi radialis and the abductor pollicis longus. A new transosseous
      approach at the base of the first metacarpal ("trans-M1" approach) is suggested
      and was used to do the ligamento-plasty. After the operation, a large skin flap
      was elevated in order to measure the distance between each surgical approach and
      the different neurovascular structures (radial artery, dividing branches of the
      superficial branch of the radial nerve and the end of the lateral cutaneous nerve
      of the forearm) and to verify the absence of neurovascular lesions. The different
      neurovascular structures at risk during this arthroscopic maneuver were the
      radial artery for the ulnar approach, the branches of the superficial branch of
      the radial nerve for all of the approaches and the ending of the lateral
      cutaneous nerve of the forearm for the radial and "trans-M1" approaches. The use
      of the approaches described allows arthroscopic trapeziectomy with the Thompson
      suspension-plasty without us having noted neurovascular lesion.

PMID- 15744449
TI  - Association between 25-hydroxy vitamin D levels, physical activity, muscle
      strength and fractures in the prospective population-based OPRA Study of Elderly
      Women.
AB  - Vitamin D supplements have been used to prevent fractures. The effect may be
      mediated through increased bone mass, but also through reduced falling
      propensity. The aim of this study was to evaluate the association between 25
      hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of
      functional performance), and fracture in ambulatory women. At baseline 25OHD was
      measured in 986 women. Fall-associated variables were investigated at baseline.
      Fractures were recorded during a 3-year follow-up. Four percent of the women had
      25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml
      (75 nmol/l). 25OHD correlated with gait speed (r =0.17, P <0.001), the Romberg
      balance test (r =0.14, P <0.001), self-estimated activity level (r =0.15, P
      <0.001), and thigh muscle strength (r =0.08, P =0.02). During the 3-year follow
      up, 119 out of the 986 women sustained at least one fracture. The Cox
      proportional hazard ratio (HR) (95% confidence interval) for sustaining a
      fracture during the follow-up was 2.04 (1.04-4.04) for the group of women with
      25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two
      of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the
      follow-up, with a non-significant HR of 1.07 (1.07-1.61). This cohort of elderly,
      ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior
      physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was
      not associated with an increased risk of fractures in this study. However, a
      subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased
      risk of fractures, which may be associated with an inferior physical activity and
      postural stability.

PMID- 15744450
TI  - Consumption of a high calcium mineral water lowers biochemical indices of bone
      remodeling in postmenopausal women with low calcium intake.
AB  - Many postmenopausal women have a calcium intake far below the recommended amount
      and, in addition to attempting to improve their diet, need a calcium supplement.
      The aim of the study was to assess the effects of the consumption of a high
      calcium mineral water (HCaMW) on biochemical indices of bone remodeling in
      postmenopausal women with low Ca intake. A 6-month randomized double-blind
      placebo-controlled trial was designed to assess the effects of a daily
      consumption of 1 liter of a HCaMW (596 mg Ca/l) on serum parathyroid hormone
      (PTH) and biochemical markers of bone remodeling in postmenopausal women with a
      dietary Ca intake lower than 700 mg/day. The placebo group drank 1 liter of a
      mineral water with a low calcium content (10 mg/l). One hundred eighty healthy
      women were recruited (mean age: 70.1+/-4.0 years); 152 completed the 6-month
      trial. The changes from baseline of biochemical indices after 6 months consisted
      of a significant 14.1% decrease of serum PTH, osteocalcin (-8.6%), bone alkaline
      phosphatase (-11.5%), serum (-16.3%) and urine (-13.0%) type-1 collagen C
      telopeptide in the HCaMW group compared to the placebo group, where all
      biochemical indices increased after 6 months. The additive effect of a small
      vitamin D supplement (400 iu/day) was also evaluated. In women receiving vitamin
      D in addition to HCaMW, the decrease in bone indices was not found to be greater
      than in women drinking only the HCaMW. A daily supplement of 596 mg of Ca through
      the consumption of 1 l of HCaMW was able to lower serum PTH and the indices of
      bone turnover in postmenopausal women with a low Ca intake. This could contribute
      to the repair of calcium deficiency and to the reduction of age-related bone loss
      in this population.

PMID- 15744451
TI  - Gender differences in trabecular bone architecture of the distal radius assessed
      with magnetic resonance imaging and implications for mechanical competence.
AB  - High-resolution magnetic resonance imaging (hrMRI) has recently made it possible
      to evaluate trabecular bone structure in vivo. Despite obvious gender differences
      in fracture incidence at the distal radius, little is known about gender
      differences in trabecular bone microarchitecture and its relationship to the
      structural strength of the forearm. The aim of this study was to determine
      trabecular bone structure in the distal radius of elderly women and men and its
      correlation with failure loads of the distal radius as determined in a fall
      configuration. Specifically, we tested the hypotheses that structural indices
      differ between women and men and that they offer information that is independent
      from BMD for predicting structural strength. Intact right arms were obtained from
      73 formalin-fixed cadavers (age 80+/-11 years, 43 women, 30 men). Trabecular
      structural indices (apparent bone volume fraction [app. BV/TV], trabecular number
      [app. Tb.N], trabecular separation [app. Tb.Sp], trabecular thickness [app.
      Tb.Th] and fractal dimension [Frac.Dim]) were assessed in the distal metaphysis,
      using hrMRI with 156 microm in-plane resolution and proprietary digital image
      analysis, while BMD was measured with dual X-ray absorptiometry (DXA). Women
      displayed significantly lower BMD (-29.8%, p <0.001), app. BV/TV (-8.2%, p <0.05)
      and app. Tb.Th (-10.2%, p <0.001) than men, whereas app. Tb.N, app. Tb.Sp. and
      fractal dimension did not differ significantly. Structural parameters differed
      between normal and osteopenic women (BV/TV: -11%, p <0.01; Tb.Th: -8%, p <0.001)
      and between normal and osteoporotic women BV/TV: -21%, p <0.001; Tb.Th: -16%, p
      <0.001). App. BV/TV, app. Tb.Th and fractal dimension provided information
      independent from BMD in the prediction of radial failure loads in multiple
      regression models. These findings imply that it should be of clinical interest to
      monitor both bone mass and trabecular microstructure for predicting osteoporotic
      fracture risk.

PMID- 15744452
TI  - Correlation between patient recall of bone densitometry results and subsequent
      treatment adherence.
AB  - Treatment of osteoporosis is often inadequate. One reason can be insufficient
      patient education following diagnostic bone densitometry (DXA). Therefore, we
      studied how patients are informed and treated following their first DXA.
      Individuals who had DXA at a rural hospital in Wisconsin were surveyed with a
      questionnaire regarding their post-test education and prescribed treatment. Their
      DXA results and the specialty of their clinician were also recorded. Eighty
      percent of the 1,014 participants were informed of their results. Of the 341
      participants who had normal bone mineral density (BMD), 63% reported correct
      results, while only 31% of the 309 who had osteopenia and 50% of the 364 who had
      osteoporosis reported correct results. Accuracy in reporting was not affected by
      the patients' age or the specialty of their clinicians. Following DXA, 339
      patients (33%) were started on medications; 86% of those remained on some
      prescribed therapy for osteoporosis, but 140 (41%) did not continue the initial
      medication. Reasons for discontinuation included side effects (48%) and cost
      (26%). Patients with low BMD who correctly reported their results were more
      likely to have received a medication and to continue to take it ( p <0.0001).
      Calcium supplements were recommended to 65% of those not taking calcium prior to
      DXA. Internists were more likely than family practitioners to recommend calcium,
      and their patients reported better medication adherence, as did those with
      osteoporosis compared with osteopenia. We conclude that, while most participants
      are informed of the results of their DXAs, the retained information may not be
      accurate. Correct understanding of DXA results may lead to higher treatment rates
      and better adherence to treatment among patients with low BMD.

PMID- 15744454
TI  - Genetic diversity of microbial eukaryotes in anoxic sediment around fumaroles on
      a submarine caldera floor based on the small-subunit rDNA phylogeny.
AB  - Recent culture-independent molecular analyses have shown the diversity and
      ecological importance of microbial eukaryotes (protists) in various marine
      environments. In the present study we directly extracted DNA from anoxic sediment
      near active fumaroles on a submarine caldera floor at a depth of 200 m and
      constructed genetic libraries of PCR-amplified eukaryotic small-subunit (SSU)
      rDNA. By sequencing cloned SSU rDNA of the libraries and their phylogenetic
      analyses, it was shown that most sequences have affiliations with known major
      lineages of eukaryotes (Cercozoa, Alveolata, stramenopiles and Opisthokonta). In
      particular, some sequences were closely related to those of representatives of
      eukaryotic parasites, such as Phagomyxa and Cryothecomonas of Cercozoa, Pirsonia
      of stramenopiles and Ichthyosporea of Opisthokonta, although it is not clear
      whether the organisms occur in free-living or parasitic forms. In addition, other
      sequences did not seem to be related to any described eukaryotic lineages
      suggesting the existence of novel eukaryotes at a high-taxonomic level in the
      sediment. The community composition of microbial eukaryotes in the sediment we
      surveyed was different overall from those of other anoxic marine environments
      previously investigated.

PMID- 15744453
TI  - Hydroxymethylglutaryl-coenzyme A reductase inhibitors and osteoporosis: a meta
      analysis.
AB  - Studies determining the association between hydroxymethylglutaryl-coenzyme A (HMG
      CoA) reductase inhibitors (statins) and bone metabolism are mixed. We conducted a
      systematic review to assess the potential impact of statins on fractures, bone
      mineral density and bone markers. We searched Medline, Embase, the Cochrane
      Library, and Federal Research in Progress (FEDRIP). Inclusion criteria consisted
      of human studies with measurable outcomes, which were rated as good or fair
      according to the United States Preventive Services Task Force (USPSTF) criteria.
      The effects of statins on bone mineral density (BMD), bone markers and fracture
      risk were independently extracted by two reviewers and were combined by use of a
      random-effects model. The 31 analyzed studies included 24 observational studies
      and seven randomized controlled trials. Overall, statin use was associated with
      fewer hip fractures (OR 0.60, 95% CI 0.45-0.78) and improved hip BMD (Z score
      0.12, 95% CI 0.05-0.19), with a non-significant reduction in vertebral fractures
      and no effect on vertebral BMD. In subgroup analysis of studies that involved
      only women there was a reduction in hip fractures (OR 0.75, 95% CI 0.60-0.95) and
      improvement in hip BMD (Z score 0.11, 95% CI 0.04-0.18). Vertebral BMD was
      unchanged, and only one study reported on vertebral fractures, finding
      improvement. Statins had only small effects on bone markers, with a decrease in
      alkaline phosphatase [standardized mean difference (SMD) -0.18, 95% CI -0.34 to 
      0.01], an increase in NTX (SMD 0.39, 95% CI 0.07-0.71), with no effect on
      osteocalcin or CTX. The statistically significant improvement in hip fracture
      risk was seen only in case-control trials, not in either the eight prospective
      trials or the two randomized controlled trials (RCTs). Statins may have a
      beneficial impact on bone metabolism and fracture risk; randomized controlled
      trials are needed to explore this association.

PMID- 15744456
TI  - Narrowed abrogation of the Angelman syndrome critical interval on human
      chromosome 15 does not interfere with epigenotype maintenance in somatic cells.
AB  - Human chromosome 15q11-q13 involves a striking imprinted gene cluster of more
      than 2 Mb that is concomitant with multiple neurological disorders manifested by
      Prader-Willi syndrome (PWS) and Angelman syndrome (AS). PWS and AS patients with
      imprinting mutation have microdeletions, which share a 4.3 kb short region of
      overlap (SRO) at the 5' end of the paternal SNURF-SNRPN gene in PWS, or on the
      maternal allele, which shares a 880 bp SRO located at the 35 kb upstream of the
      SNURF-SNRPN promoter in AS. Recent studies have revealed an essential role of PWS
      SRO in the postzygotic maintenance of the appropriate epigenotype on the paternal
      chromosome. For AS-SRO, however, there is insufficient experimental evidence
      exists to determine the direct functions. Here we show that the complete deletion
      of AS-SRO does not cause any anomalies of imprinted gene expression or DNA
      methylation on the mutated human chromosome 15, further supporting the idea that
      AS-SRO is dispensable for post implantation imprint maintenance. This implies
      that AS-SRO is not essential for the robust epigenotype preservation in somatic
      cells.

PMID- 15744455
TI  - Association analysis of signal transducer and activator of transcription 4
      (STAT4) polymorphisms with asthma.
AB  - The signal transducer and activator of transcription 4 (STAT4) on chromosome
      2q32.2-q32.3 is known to be essential for mediating responses to interleukin 12
      in lymphocytes and regulating the differentiation of T helper cells. In an effort
      to discover additional polymorphism(s) in genes in which variant(s) have been
      implicated in asthma, we investigated the genetic polymorphisms in STAT4 to
      evaluate it as a potential candidate gene for a host genetic study of asthma. By
      direct DNA sequencing in 24 individuals, we identified 12 sequence variants
      within introns and their flanking regions, including the 1.5 kb promoter region
      of STAT4. Among them, seven common polymorphic sites were selected for genotyping
      in our asthma cohort (502 asthmatic patients, 164 normal controls). Using
      logistic regression analysis for association with the risk of asthma, while
      controlling for age, gender, and smoking status as covariates, no significant
      associations with the risk of asthma were detected. However, one single
      nucleotide polymorphism (SNP) in intron 11 (+90089T--> C) and two haplotypes
      showed positive association (P= 0.03, 0.03 and 0.03, respectively) with
      production of specific IgE to Dermatophagoides farinae (D.f.) or Dermatophagoides
      pteronyssinus (D.p.) among asthmatic patients. The minor allele frequencies of
      +90089T--> C and BLOCK2-ht1 were higher (0.54 and 0.47, respectively) among
      individuals who produced specific IgE to D.f. or D.p. than frequencies (0.47 and
      0.39, respectively) among individuals who did not produce specific IgE (OR=1.38
      and 1.40, respectively). Our findings suggest that polymorphisms in STAT4 might
      be one of the genetic factors for the risk of production of specific IgE to mite
      allergens.

PMID- 15744457
TI  - Association of eotaxin-2 gene polymorphisms with plasma eotaxin-2 concentration.
AB  - Chemokine (C-C motif) ligand 24 (CCL24, eotaxin-2) is a CC chemokine that
      recruits and activates cells bearing the CC chemokine receptor 3, which play a
      major role in asthma. Previously, we observed a significant association between a
      single nucleotide polymorphism (SNP) in eotaxin-2 (CCL24+1272A--> G) and a lower
      risk of asthma. Consequently, this study has followed up on those genetic effects
      by evaluating the association between the SNP and plasma eotaxin-2 concentration
      in 172 asthmatics and 135 normal controls. Asthmatics had significantly higher
      plasma eotaxin-2 levels than did normal controls (P=0.02). The SNP (CCL24+1272A-
      > G) and two haplotypes (ht2 and ht6) were strongly associated with plasma
      eotaxin-2 levels in asthmatics (CCL24+1272A--> G: P=0.006, ht2: P=0.006, and ht6:
      P=0.002). The CCL24+1272A--> G allele and the ht2 and ht6 haplotypes showed a
      gene-dose effect on the plasma eotaxin-2 levels in asthmatics (P=0.005-0.032). In
      conclusion, the susceptibility of patients with asthma to high eotaxin-2
      production may be due to genetic effects of the CCL24+1272A--> G polymorphism,
      ht2 and ht6 haplotypes.

PMID- 15744458
TI  - Characterisation of novel mutations in Cockayne syndrome type A and xeroderma
      pigmentosum group C subjects.
AB  - We report that a subject with Cockayne syndrome type A (CS3BE) was a compound
      heterozygote for mutations in CKN1, the gene encoding the CSA protein (MIM
      216400). CS3BE displayed a novel missense mutation (A160V) and a previously
      described nonsense mutation (E13X). Although residing between the second and
      third WD-40 repeats characteristic of the CSA protein, A160 is completely
      conserved in all species that possess a CKN1 homologue. We also describe a
      mutation in a previously uncharacterised xeroderma pigmentosum group C subject
      (XP8CA) in the XPC gene (MIM 278720). XP8CA was homozygous for a 2 bp TG deletion
      in codon 547 resulting in premature termination at codon 572. Immunoblotting of
      XP8CA extracts confirmed the absence of full-length XPC protein that was present
      in unaffected cell lines.

PMID- 15744459
TI  - Volume exclusion effects in the ground-state dominance approximation for
      polyelectrolyte adsorption on charged interfaces.
AB  - We consider the problem of polyelectrolyte molecules adsorbing on oppositely
      charged interfaces. For sufficiently long chains, the ground-state dominance
      approximation can be used which results in a (semi-)analytical solution of the
      self-consistent field equations (aSCF). Whereas existing aSCF theory assumes a
      low polyelectrolyte density, here the required electrostatic corrections for a
      high polymer density are implemented. Adsorbed polymer excludes volume for the
      solvent and small ions, a volume effect that also leads to a reduced dielectric
      permittivity and a resulting polarization term in the exchange potential.
      Calculations show the influence of volume exclusion on the polymer density
      profile.

PMID- 15744460
TI  - Symmetry-breaking transitions and dissociation of two-dimensional Plateau
      borders.
AB  - We have experimentally studied the dissociation/coalescence of internal Plateau
      borders (PBs) in simple monolayer bubble clusters, as a result of changing the
      liquid fraction. At large liquid content, the clusters consist of n bubbles of
      the same size, symmetrically placed around an internal n-sided PB (n-PB). On
      decreasing the liquid fraction we observed symmetry-breaking transitions in the 4
      and 5-bubble clusters (but not in the 3-bubble cluster), followed by
      dissociation of the PBs. We used the Surface Evolver to determine the various
      equilibrium configurations of the corresponding two-dimensional wet clusters and
      their surface energies. The sequence of 4-bubble cluster configurations observed
      on varying the liquid fraction correlates qualitatively with that predicted on
      the basis of Surface Evolver calculations. The same is not true of the 5-bubble
      cluster.

PMID- 15744461
TI  - Haem conformation of amphibian nytrosylhaemoglobins detected by XANES
      spectroscopy.
AB  - We investigated for the first time the haem stereochemistry in the nitrosylated
      derivative of two amphibian haemoglobins, Xenopus laevis and Ambystoma mexicanum,
      by means of X-ray absorption spectroscopy technique with the aim to explain the
      relationships between the active site structure and physiological function of
      these proteins, compared to that from humans. Our results show that while the Fe
      site local structure of human HbNO is modulated by an allosteric effector such as
      IHP shifting the T-R equilibrium towards the T-state, the Fe site local structure
      of amphibians HbNO is stabilized in a particularly tensed T-state also without
      IHP.

PMID- 15744462
TI  - Ventricular reverse remodeling and 6-month outcomes in patients receiving cardiac
      resynchronization therapy: analysis of the MIRACLE study.
AB  - OBJECTIVE: The objective of this analysis was to determine if there were
      differences in ventricular reverse remodeling and 6-month outcome with cardiac
      resynchronization therapy (CRT) among specific subgroups enrolled in the
      Multicenter InSync Randomized Clinical Evaluation (MIRACLE) Study. BACKGROUND:
      Analysis of major subgroups receiving CRT is important in determining who may be
      most likely to benefit, since all patients who receive CRT do not demonstrate
      improvement. METHODS: Differences in response to CRT between subgroups based on
      baseline echocardiographic parameters, New York Heart Association (NYHA) class,
      age, gender, beta blocker use, and etiology of heart failure (HF) were analyzed
      for the clinical end points of the study as well as 6-month HF re-hospitalization
      or death. RESULTS: The benefit of CRT over control was similar in all subgroups
      with respect to all clinical endpoints. However, non-ischemic HF patients had
      greater improvements with CRT compared to ischemic HF patients in left
      ventricular end diastolic volume (P < 0.001) and ejection fraction (EF) (6.7%
      increase vs. 3.2% [P < 0.001]). Greater improvements in EF were also seen in
      those patients with less severe baseline mitral regurgitation (MR) (P < 0.001).
      Women but not men receiving CRT were more likely to be event-free from first HF
      hospitalization or death compared to the control group (Hazard Ratio = 0.157).
      CONCLUSIONS: The benefits of CRT with respect to EF and reverse remodeling were
      greater in patients with non-ischemic HF and less severe MR. Women may also
      derive more benefit than men with respect to the occurrence of HF hospitalization
      or death.

PMID- 15744463
TI  - Late occurrence of adenosine-sensitive focal junctional tachycardia in complex
      congenital heart disease.
AB  - BACKGROUND: Although supraventricular tachycardia in complex congenital heart
      disease (CHD) has been reported after surgical repair, its exact
      electrophysiologic identification has been limited to intraatrial reentrant
      tachycardia (IART). Moreover, junctional tachycardia (JT) has not previously been
      described as a cause of late postoperative arrhythmia. METHODS AND RESULTS: Since
      1993, a total of 12 patients with congenital heart disease presented with
      paroxysmal focal JT. The patients with only typical immediate postoperative
      junctional ectopic tachycardia were excluded. Medical records, standard
      electrocardiography and Holter monitoring were reviewed. An intracardiac
      electrophysiologic (EP) study was performed in 11 patients. Ten patients were in
      post-Fontan status (5.7% of total Fontan survivors). Focal JT occurred more
      frequently in heterotaxy syndrome among the Fontan survivors (7/52 vs. 3/124; P <
      0.05). The commonest anatomy of the atrioventricular (AV) junction was complete
      AV canal in 8 patients. EP characteristics of focal JT were as follows: (1)
      various tachycardia mechanisms were identified (increased automaticity or a
      triggered mechanism in 6/11, and focal reentry in 5/11, including one concealed
      nodofascicular pathway) (2) ventriculoatrial conduction during tachycardia was
      either dissociation (7/12) or variable (5/12) (3) All JTs were terminated by
      adenosine. Class III antiarrhythmic agent was effective in 5/6. His bundle
      ablation was performed in one Fontan patient, who already had pacemaker because
      of accompanying intractable IART and sinus node dysfunction. CONCLUSION: Focal JT
      may be a source of late term supraventricular tachycardia in patients with
      complex CHD. The tachycardia mechanism was either automatic/triggered or
      reentrant. In all patients, JT was effectively terminated by adenosine.

PMID- 15744464
TI  - Inability to cannulate the coronary sinus in patients with supraventricular
      arrhythmias: congenital and acquired coronary sinus atresia.
AB  - We report 4 cases of congenital and acquired coronary sinus ostial atresia
      incidentally found during electrophysiologic assessment for supraventricular
      arrhythmias. Congenital variants consisted of coronary sinus drainage
      predominantly via persistent left superior vena cavae and partial coronary sinus
      unroofing into the left atrium. The acquired variant was inadvertently produced
      during surgery for cor triatriatum. A variety of electrophysiologic substrates
      including right and left-sided accessory pathways and both typical and atypical
      AV nodal reciprocating tachycardia were identified. Approaches to imaging and
      accessing the coronary sinus when the os cannot be cannulated are discussed,
      including a search for right atrial accessory venous collaterals, venography to
      rule-out a persistent left superior vena cava, and coronary angiography.

PMID- 15744465
TI  - Upper rate response of biventricular pacing devices.

PMID- 15744466
TI  - Impact of changing activation sequence on bipolar electrogram amplitude for
      voltage mapping of left ventricular infarcts causing ventricular tachycardia.
AB  - INTRODUCTION: Wavefront direction is a determinant of bipolar electrogram
      amplitude that could influence identification of low amplitude regions indicating
      infarction or scar. METHODS: To assess the importance of activation sequence on
      electrogram amplitude 11 patients with prior infarction and ventricular
      tachycardia were studied. At 819 left ventricular sites bipolar electrograms were
      recorded during atrial pacing and ventricular pacing, followed by unipolar pacing
      with a stimulus of 10 mA at 2 ms. Sites with a pacing threshold > 10 mA were
      designated electrically unexcitable scar. RESULTS: Areas of low voltage (< or
      =1.5 mV) were present in all patients. Atrial paced and ventricular paced
      electrogram amplitudes were strongly correlated (r = 0.77; P < 0.0001). Changing
      the activation sequence (from atrial pacing to ventricular pacing) produced a >
      50% change in electrogram amplitude at 28% of sites and a > 100% change at 10% of
      sites, but only 8% of sites had an electrogram amplitude classified as abnormal
      (< or =1.5 mV) with one activation sequence and normal (> 1.5 mV) with the other
      activation sequence. Electrically unexcitable scar (6% of sites) was associated
      with lower electrogram amplitude but could not be reliably identified based on
      electrogram amplitude alone for either activation sequence. CONCLUSION: Voltage
      maps created with bipolar recordings using these methods should be relatively
      robust depictions of abnormal ventricular regions despite variable catheter
      orientation and activation sequences that might be produced by different rhythms.

PMID- 15744467
TI  - A streamlined, anchored, anatomical approach to ablation of atrioventricular
      nodal reentry tachycardia: preliminary report of the first 25 cases.
AB  - A pseudo r' in V1 during supraventricular tachycardia (SVT), but not during sinus
      rhythm is pathognomonic for AV nodal re-entry tachycardia (AVNRT). During
      radiofrequency (RF) energy delivery, stability of the catheter tip is crucial.
      Intra-procedural catheter and patient movement as well as abrupt rhythm changes
      can lower efficacy, prolong procedural time, and contribute to the risk of AV
      block. OBJECTIVES: A novel streamlined approach using a single sheath and two
      catheters was evaluated that leverages the patient's own anatomy to help
      stabilize catheter position during RF application and localize RF targets.
      METHODS: Twenty-five consecutive patients presenting with documented SVT were
      ablated using a single sheath technique with only two catheters. A 12F 75 cm
      sheath was inserted via the right femoral vein and its tip is placed at base of
      the right atrium (RA). Through this sheath a 6F coronary sinus (CS) catheter and
      6F ablation catheter are placed. After confirming the diagnosis of AVNRT, the
      ablation catheter tip is positioned anterior to the CS os in the slow pathway
      region. During RF application, the mobility constraints of the "sheath-catheter
      catheter" complex provide excellent electrogram and catheter stability by taking
      advantage of the "collaring" effect of the sheath which is in turn "anchored" to
      the diagnostic CS catheter. RESULTS: Acute procedural success was 100% with no
      apparent complications. Flouroscopy time was modest (8.5 min (range 3.1-22)) as
      were the case times (mean 120 min (range 52-206)). Cost savings compared to "3
      cath-3 sheath" approach was 113 U.S. dollars and would be much larger if compared
      to newer non-flouroscopic navigational systems or using alternative ablation
      energy sources. CONCLUSIONS: This new approach minimizes ablation catheter tip
      movement on the slow pathway region providing a safe, successful, speedy, and
      economical alternative to a traditional 3 or 4 catheter approach in appropriately
      selected SVT patients.

PMID- 15744468
TI  - Implantable dual-chamber defibrillator for the selective treatment of spontaneous
      atrial and ventricular arrhythmias: arrhythmia incidence and device performance.
AB  - INTRODUCTION: Atrial tachyarrhythmias are a common co-morbidity in patients with
      an ICD indication. Recently introduced ICD's are equipped to independently detect
      and treat atrial and ventricular tachyarrhythmias. The purpose of this
      prospective study was to evaluate the incidence and termination of spontaneous
      atrial and ventricular tachyarrythmias in patients with a history of atrial
      tachyarrhythmias. METHODS AND RESULTS: Ninety patients, 70% male with an ICD
      indication and history of atrial tachyarrhythmia (LVEF 45 +/- 6%, [AT/AF
      indication 55 +/- 10, AT/VT 45 +/- 16], 46% CAD) were enrolled and 89 were
      implanted with a VENTAK PRIZM AVT (Guidant). Spontaneous atrial and ventricular
      tachyarrhythmias were printed and evaluated during an average follow-up period of
      272 +/- 72 days utilizing the stored intracardial electrogram function of the
      device. Nineteen patients (21%) presented had only atrial tachyarrhythmias, 32
      patients (36%) had both atrial and ventricular tachyarrhythmias and 18 patients
      (20%) had only ventricular tachyarrhythmias. Patients with only atrial
      tachyarrhythmias had a total of 3274 atrial episodes; 2002 terminated
      spontaneously, 1264 were treated with ATP and 8 with shock therapy. ATP was
      successful in 735 (58%) of 1264 episodes. Patients with both atrial and
      ventricular tachyarrhythmias had 7277 documented atrial tachyarrhythmias, 5231
      terminated spontaneously, 1153 of 2009 were terminated by ATP (57.4%) and 37 by
      shock therapy (20 patient controlled). Atrial tachyarrhythmias identified as
      atrial flutter (AT) by the atrial rhythm classification (ARC) algorithm had a
      higher ATP conversion success rate than episodes identified as atrial
      fibrillation (AF); 66.7% for AT and 26.4% for AF. Patients with only ventricular
      tachyarrhythmias had 690 documented episodes, 401 terminated spontaneously, 248
      (85.8%) were terminated by ATP and 41 by shock. CONCLUSION: Seventy-seven percent
      of patients with an ICD indication had spontaneous atrial and/or ventricular
      tachyharrhythmias within the first 6 months after ICD implantation. ATP therapy
      terminated 58% of all atrial tachyarrhytmias and 66.7% of the atrial flutters.
      The dual chamber ICD detected, classified and terminated all ventricular
      tacharrhythmias appropriately.

PMID- 15744469
TI  - Coronary sinus lead placement via the internal jugular vein in patients with
      advanced heart failure: a simplified percutaneous approach.
AB  - BACKGROUND: Placement of coronary sinus (CS) leads is usually achieved via the
      left cephalic-axillary-subclavian (CAS) venous system. In some cases, however,
      such as lack of venous access a right side approach is required. Cannulation of
      the CS via the right CAS vein is often technically difficult, leaving the right
      IJ vein as a suitable alternative. OBJECTIVE: The feasibility of IJ vein as a
      conduit for transvenous left ventricular (LV) pacing in patients with heart
      failure (HF) has not been reported. METHODS AND RESULTS: Between July 2002 and
      April 2004, we implanted 339 biventricular devices in patients with moderate-to
      severe HF. In 15 patients with similar clinical characteristics, in whom the left
      CAS vein could not be used, the CS leads were placed via the right CAS venous
      system (n = 5) or the IJ vein (n = 10). The ten patients (6 men and 4 women; age
      66 +/- 15 years; LV ejection fraction .19 +/- .07; QRS duration 183 +/- 35 ms)
      who required IJ CS lead placement had no procedure related complications and all
      retained appropriate LV pacing and showed significant improvement in HF symptoms
      after a median follow-up of 12 months (6 to 22 months). CONCLUSIONS: Thus, in
      patients with HF for whom the traditional CAS venous approach cannot be used
      (left side) or is technically difficult (right side), CS leads can be deployed
      safely via the right IJ vein. In these situations, it seems appropriate to
      consider this approach prior to the more invasive epicardial approaches.

PMID- 15744470
TI  - History. George Ralph Mines (1886-1914).

PMID- 15744472
TI  - Acculturation, parent-child acculturation differential, and chronic disease risk
      factors in a Mexican-American population.
AB  - Acculturation is typically defined in terms of individual responses to a dominant
      culture. In the present study, we examined the effects of different levels of
      acculturation among family members. Specifically, we looked at the health and
      risk behavior in Mexican-American children as related to a variety of
      psychosocial predictors, especially the differences in orientation toward Mexican
      and Anglo-American cultures between them and their parents. Mother and child
      pairs (n = 106) noted their orientation toward both Anglo and Mexican cultures.
      Children's dietary and sedentary behaviors, tobacco and alcohol use (and
      susceptibility to use), and depressive symptoms were also measured. Males were
      more likely to be sedentary and consume higher levels of total fat and saturated
      fat, whereas girls reported higher levels of depression. Anglo-oriented youth
      consumed lower levels of calories from fat but also more alcohol than did their
      Mexican-oriented counterparts. The latter was particularly the case among those
      children who were relatively more Anglo oriented than were their parents. Parent
      child acculturation differential in terms of the differences in Mexican
      orientation, in comparison, predicted susceptibility to tobacco use. However, the
      sum of the absolute values of these two differences predicted only lifetime
      alcohol use, and in a counter-intuitive direction. This familial measure of
      acculturation shows some promise, but additional formative research is needed to
      operationalize this construct.

PMID- 15744473
TI  - International migration and infant health in Mexico.
AB  - This paper examines the flip side of the epidemiological paradox, namely the
      relationship between international migration experience and positive infant
      health outcomes in Mexico. Building upon past research that has explored the role
      of economic remittances in contributing to the positive relationship between
      international migration and birth outcomes in sending country communities, the
      present analysis focuses on the noneconomic effects of paternal migration
      experience on infant health. The data come from a hospital-based postpartum
      survey (HPS 2001) recently completed in two high-migrant sending states of
      Western Mexico. The findings demonstrate that the positive effect of
      international migration on infant health occurs in the context of considerable
      loss of social support and high stress levels. Socioeconomic improvements
      facilitated by the receipt of remittances, coupled with positive health
      behaviors, are two factors that contribute to this protective effect.

PMID- 15744474
TI  - Use of alternative folk medicine by Mexican American women.
AB  - Nontraditional health care resources available to Mexican Americans are many. The
      Mexican culture is rich with alternative health and illness beliefs and remedies
      which have their origins in ancient Mestizo/Indian folklore which viewed the
      causes of illness to include social, spiritual, and physical forces. This
      perception calls for culturally relevant folk practitioners who can treat all
      aspects of the perceived illness. This study of 70-Mexican American women
      explored their knowledge of and use of alternative Mexican folk medical
      practitioners in their own health maintenance. Results provided some evidence
      that, even among highly assimilated Mexican American women, there persist
      traditional, indigenous beliefs, and practices.

PMID- 15744475
TI  - An audiotaped mental health evaluation tool for Hispanic immigrants with a range
      of literacy levels.
AB  - Debilitating mental illness is treatable if found. There is no validated self
      administered mental illness evaluation tool for immigrant Hispanic farm workers
      with variable literacy levels. This study tested sensitivity and specificity of
      an audiotaped survey developed for low literacy levels compared with standard
      interview instruments. Subjects from 11 migrant camps completed a self
      administered audiotaped survey in Spanish to diagnose major depression, substance
      abuse, panic and generalized anxiety, and domestic violence. Primary care clinics
      assisted in finding camps and provided follow-up treatment. For 154 men and 156
      women, the audio tool was most sensitive for major depression and specific for
      anxiety disorder, alcohol abuse, and domestic violence. Seventy percent of those
      diagnosed with major depression received appropriate treatment. This study
      validated an inexpensive, self-administered audio tool to evaluate the mental
      health of immigrant Hispanic farm workers with a wide range of literacy levels.

PMID- 15744476
TI  - Welfare and immigration reform and use of prenatal care among women of Mexican
      ethnicity in San Diego, California.
AB  - Foreign-born women and, in particular, Hispanic foreign-born women, are less
      likely to have insurance, are less likely to have insurance that covers prenatal
      care, and are less likely to utilize prenatal care compared with US-born Hispanic
      women. Significant concern has been raised regarding the ability of immigrant
      women to access prenatal care services because of severe restrictions imposed on
      immigrants' eligibility for Medicaid-funded services following the passage in
      1996 of the federal Personal Responsibility and Work Opportunity Reform Act
      (PRWORA) and the Illegal Immigration Reform and Immigrant Responsibility Act
      (IIRAIRA). We conducted an interview-based study of prenatal care utilization
      with women of Mexican ethnicity and diverse immigration statuses in San Diego
      County, California. Our findings indicate that, despite increased levels of fear
      associated with recent immigration and with undocumented status, there were no
      statistically significant differences across immigration statuses in length of
      time to receipt of medical care for gynecological events and for prenatal care.

PMID- 15744477
TI  - Uninsured working immigrants: a view from a California county.
AB  - We inform a county's efforts to provide health insurance to uninsured working
      immigrants-a group left out of national and state strategies that aim to expand
      coverage. We analyzed a population-based survey data administered in English,
      Spanish, Cantonese, Mandarin, Korean, Vietnamese, and Dari on 5,540 nonelderly
      adult workers in Alameda County, California. The study models the likelihood of
      employment-based coverage, estimates the eligibility for public programs, and
      evaluates the affordability of average employee share of premiums by citizenship
      status and years lived in the United States (tenure). Immigrant workers in
      Alameda County are disproportionately uninsured. They constitute 29% of the
      employee labor force but 54% of uninsured employees. Employment-based coverage
      increased with citizenship and length of stay (tenure) in the United States.
      Noncitizens with less than 5 years residency in the United States faced the
      greatest disadvantage in securing employment-based coverage, an effect that is
      greater than disadvantages associated with race/ethnicity. A citizenship-tenure
      divide existed in obtaining employment-based coverage, suggesting that policies
      focusing on noncitizen and new immigrant workers would greatly relieve the
      disparate uninsured rates among workers. The expansion of nonemployment-based
      coverage programs would cover more than 30% of Alameda County's uninsured
      immigrant workers; but subsidies will also be needed for the lowest-income
      workers who are not eligible for these programs.

PMID- 15744478
TI  - Simit epidemiological multicentric study on hospitalized immigrants in Italy
      during 2002.
AB  - The aim of this article is to retrospectively evaluate the patient
      characteristics and the most common infectious diseases in immigrant patients
      hospitalized in 46 Italian infectious disease clinics during 2002. The main
      Italian infectious disease clinics were invited to fill in a questionnaire that
      regarded the number and type of hospital admissions, the country of origin, and
      demographic features (age, sex, and resident state) of immigrants. A total of 46
      clinics including 2255 patients participated in the study. Most patients were men
      (63%) with an age between 16 and 40 years (63.4%) covered by the National Health
      Service (71%) and coming from Africa (44.3%). The main infectious diseases
      observed were: 378 (16.76%) cases of HIV infection, 303 (13.43%) cases of
      tuberculosis diseases, 282 (12.5%) cases of various forms of viral hepatitis, 177
      (7.84%) cases of respiratory diseases, and 196 (8.69%) gastrointestinal diseases.
      Tropical diseases found were 134 (5.94%) including 95 cases of malaria (70.9%).
      In conclusion, a broad range of diseases was noted in immigrants which were
      directly correlated with conditions of poverty. Only a few tropical diseases were
      diagnosed and therefore the immigrant should not be considered as an infectious
      disease carrier.

PMID- 15744479
TI  - Redox options in two-dimensional electrophoresis.
AB  - Two-dimensional electrophoresis is usually run on fully reduced samples. Under
      these conditions even covalently bound oligomers are dissociated and individual
      polypeptide chains may be fully unfolded by both, urea and SDS, which maximizes
      the number of resolved components and allows their pI and M(r) to be most
      accurately evaluated. However, various electrophoretic protocols for protein
      structure investigation require a combination of steps under varying redox
      conditions. We review here some of the applications of these procedures. We also
      present some original data about a few related samples -- serum from four
      species: Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus -- which we
      run under fully unreduced and fully reduced conditions as well as with reduction
      between first and second dimension. We demonstrate that in many cases the
      unreduced proteins migrate with a better resolution than reduced proteins, mostly
      in the crowded 'alpha-globulin' area of pI 4.5-6 and M(r) 50-70 kDa.

PMID- 15744481
TI  - [O-twist marker for post-interventional marking in imaging of suspected breast
      lesions].
AB  - AIM: The aim of this study was to develop a marker clip for use in minimally
      invasive diagnostics of breast cancer that can be placed and visualized during
      ultrasonography, mammography, and magnetic resonance imaging. METHODS: The newly
      developed O-twist marker consists of three 0.15-mm biocompatible nitinol wires
      twisted together to form rings with a diameter of 2.5 mm. These are inserted
      elongated into a 20G cannula. The marker is ejected into the tissue through a
      mandrin and reverts to its predetermined ring form. RESULTS: The multiple curves
      of the surface render the marker highly visible. Its geometry permits secure
      anchorage even in larger biopsy cavities and additionally prevents migration
      within the tissue. CONCLUSION: The O-twist marker is applicable for all
      examination modalities and biopsy needles or biopsy systems and represents an
      important development for breast cancer diagnostics.

PMID- 15744480
TI  - [Effects of distress and coping on quality of life in HIV-positive patients:
      results of a longitudinal study].
AB  - Preserving health-related quality of life (QOL) is an important approach with HIV
      positive patients. In a longitudinal study over 3 years, with three measurements
      each 18 months, we examined 56 of these patients for the influence of distress
      and coping (assessed by interviews) on physical, cognitive-emotional, and social
      QOL (using the SEL questionnaire). The patients were 32.9 years old on average,
      with 28.3 months since diagnosis. Seventy percent were male, 82% asymptomatic,
      14% with ARC, and 4% with AIDS. Forty-five percent had been infected by
      homosexual intercourse, 14% by heterosexual intercourse, and 41% by iv drug
      abuse. The patients reported significantly worse physical and cognitive-emotional
      QOL than healthy subjects. Those HIV-positive persons with great distress showed
      significantly lower QOL scores. Multiple analyses of regression showed evasive
      regressive coping at the T1, T2, and T3 levels as negative predictors, vs active,
      problem-focused coping as a positive predictor for nearly all QOL parameters at
      T3. HIV-positive patients with ARC or AIDS reported more physical complaints and
      lower physical QOL than asymptomatic persons. Physicians should suggest
      psychosocial support to patients with poor QOL scores.

PMID- 15744482
TI  - [Sonographically guided, minimally invasive biopsy of uncertain mammary lesions.
      Clinical experience with a new biopsy system].
AB  - METHODS: We performed Vacora biopsy on 53 patients for minimally invasive breast
      diagnostics. Each histologically malignant lesion underwent surgery. The
      histopathology of the Vacora biopsy was then compared to the surgical report.
      When there was a discrepancy between Vacora histopathology and the report, the
      patient underwent open biopsy. In all patients with benign histopathology
      results, sonography was performed 5-7 days after biopsy and after 3 months.
      RESULTS: We performed biopsies on two lesions in eight patients, and on three
      lesions in one patient. Mean age of the patients was 52.1+/-12.8 years. A total
      of 62 lesions were examined. Mean size of the lesions was 13.3+/-9.6 mm. Fourteen
      (26.4%) were malignant (n=2 DCIS, n=12 invasive carcinoma). Histological grading
      was identical for Vacora biopsy and the surgical specimens. One case showed ADH
      by Vacora biopsy, which was confirmed by open biopsy. Vacora biopsy generated one
      false negative. There were a total of 36 benign lesions. CONCLUSION: Vacora
      biopsy under sonographic guidance is a method which is easy to handle,
      diagnostically accurate and without severe complications. Due to higher costs in
      comparison to high speed core biopsy, Vacora biopsy should be performed only in
      cases in which high speed core biopsy is not expected to result in a valid
      result.

PMID- 15744483
TI  - [Clinical results of digital mammography].
AB  - Digital mammography is the technology of the future in breast diagnosis. This
      article provides an overview of all digital mammography units admitted by the
      Food and Drug Administration (FDA), results of clinical studies, soft copy
      reading, CAD (computer aided detection), and presents an overview on possible
      further developments. It is obvious that clinical results are equivalent to
      conventional screen film mammography and digital mammography.

PMID- 15744484
TI  - Light-dependent expression of superoxide dismutase from cyanobacterium
      Synechocystis sp. strain PCC 6803.
AB  - The oxygenic phototrophic cyanobacterium Synechocystis sp. strain PCC 6803
      inevitably evolves superoxide during photosynthesis. Synechocystis 6803 contains
      only one type of superoxide dismutase, designated as SodB; therefore, this
      protein plays an important role in preventing oxidative damages caused by light.
      Because there was no direct evidence that SodB in Synechocystis 6803 could be
      regulated by light, the relationship between SodB and light was investigated in
      the present study. The activity of SodB from the cells grown in continuous light
      culture was about 3.5-fold higher than that from the cells cultivated in
      continuous dark. Illumination maximally activated SodB within 12 h. The level of
      sodB mRNA increased 12-fold by light, and that of SodB protein proportionally.
      Therefore, the expression and activity of SodB from Synechocystis 6803 were
      dependent on the light.

PMID- 15744485
TI  - Biotransformation of dichloro-, trichloro-, and tetrachlorodibenzo-p-dioxin by
      the white-rot fungus Phlebia lindtneri.
AB  - The model polychlorinated dibenzo-p-dioxins (PCDDs) 2,7-dichloro-, 2,3,7
      trichloro, 1,2,6,7-, 1,2,8,9-, and 1,3,6,8-tetrachlorodibenzo-p-dioxin were used
      as substrates for a degradation experiment with the white-rot fungus Phlebia
      lindtneri. 2,7-Dichlorodibenzo-p-dioxin (2,7-diCDD) was biotransformed to
      hydroxylated diCDD and methoxylated diCDD. With the exception of 1,3,6,8
      tetrachlorodibenzo-p-dioxin, the tri- and tetrachlorodibenzo-p-dioxins were
      biotransformed to hydroxyl and methoxyl compounds by P. lindtneri. The
      degradation rate of 1,2,6,7-tetrachlorodibenzo-p-dioxin was higher than that of
      2,3,7-trichlorodibenzo-p-dioxin and no degradation of 1,3,6,8-tetrachlorodibenzo
      p-dioxin was observed. These results indicate that the degradation of these PCDDs
      depends on the chlorination patterns of the substrates. This is the first report
      of the hydroxylation and methoxylation of tri- to tetra-CDDs by a fungal strain.

PMID- 15744486
TI  - Biotechnological production and applications of coenzyme Q10.
AB  - Coenzyme Q10 is widely used as an essential component of ATP generation in the
      oxidative phosphorylation process and as an antioxidant preventing lipid
      peroxidation and scavenging superoxide. It is also recommended as a supplement to
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Research efforts on
      the production of coenzyme Q10 by microorganisms focus on the development of
      potent strains by conventional mutagenesis and metabolic engineering, analysis
      and modification of the key metabolic pathways and optimization of fermentation
      strategies. Especially, random mutants with drugs resistance show a high coenzyme
      Q10 concentration. Metabolic engineering techniques have been applied to improve
      coenzyme Q10 production. The key enzymes involved in the coenzyme Q10
      biosynthesis pathway have been cloned and expressed in Escherichia coli. The
      rational design of metabolic pathways in combination with engineering
      optimization of fermentation processes could facilitate the development of viable
      bioconversion processes.

PMID- 15744487
TI  - Analysis of mating-dependent transcription of Blakeslea trispora carotenoid
      biosynthesis genes carB and carRA by quantitative real-time PCR.
AB  - The zygomycete fungus Blakeslea trispora is used commercially as natural source
      of beta-carotene. beta-Carotene production is strongly induced during mating of
      two strains of the opposite sex and results in the production of the pheromone
      trisporic acid, which in turn stimulates enhanced beta-carotene biosynthesis.
      beta-Carotene production is due to the enzymatic activity of phytoene synthase,
      lycopene cyclase and phytoene dehydrogenase. The corresponding genes, carRA and
      carB, were isolated from a cosmid library generated from B. trispora strain
      ATCC14272. The steady state level of carB and carRA mRNA transcripts under
      different mating conditions was monitored by both northern blot analysis and
      quantitative real-time PCR. The steady state levels of carRA and carB mRNA of non
      mated and mated B. trispora were quantified relative to transcript levels of the
      translation elongation factor 1alpha-encoding tef1 gene, since tef1 is
      transcribed independently of mating. Transcription levels of both carB and carRA
      were strongly induced only under mating conditions. These data suggest that beta
      carotene production in B. trispora is due to increased transcription of the
      biosynthesis genes carB and carRA.

PMID- 15744488
TI  - Decreased incidence of disease caused by Sclerotinia sclerotiorum and improved
      plant vigor of oilseed rape with Bacillus subtilis Tu-100.
AB  - Sclerotinia sclerotiorum causes serious yield losses in oilseed crops worldwide.
      Bacillus subtilis Tu-100 significantly reduced (P< or =0.05) the incidence of
      disease caused by S. sclerotiorum on oilseed rape at harvest in two trials
      conducted in fields artificially infested with this pathogen. Mean plant dry
      weight was significantly greater (P< or =0.05) and mean plant length was
      significantly greater (P< or =0.07) at the seven-true-leaf stage with the Tu-100
      treatment than with the control. Mean seed yield per 120 plants at harvest was
      significantly greater (P< or =0.05) in the second field trial with treatments
      containing isolate Tu-100. B. subtilis Tu-100 also promoted the growth of
      hydroponically grown oilseed rape. Plants were approximately 15% greater in dry
      weight (P< or =0.0001) and 6% greater in length (P< or =0.0025) when grown in the
      presence of isolate Tu-100 in Hoagland's solution, compared with the
      noninoculated control. In gnotobiotic studies, the lacZ-tagged strain B. subtilis
      Tu-100(pUC18) was detected within all roots of oilseed rape. Isolate Tu-100 did
      not persist in the ectorhizosphere of oilseed rape. Populations of this isolate
      decreased from 8.5x10(8) colony-forming units (CFU) per seed to approximately
      10(2) CFU in the plant ectorhizosphere within 30 days of sowing in autoclaved
      soil.

PMID- 15744489
TI  - [Intraocular inflammations. A diagnostic and therapeutic challenge].

PMID- 15744490
TI  - [Transpupillary thermotherapy for occult choroidal neovascularizations].
AB  - PURPOSE: This contribution describes the results of transpupillary thermotherapy
      (TTT) for age-related exudative macular degeneration (AMD) with regression.
      PATIENTS AND METHODS: In exudative AMD with occult choroidal neovascularization
      (CNV), transpupillary thermotherapy (TTT) was performed using a diode laser
      (Iridex) in unselected patients. Before therapy and 1, 3, and 6 months after the
      initial treatment the patients were examined clinically. Additionally threshold
      testing in the 10 degrees field (Humphrey) and fluorescein angiographies were
      documented at all check-ups. RESULTS: With respect to vision, differences in the
      slope of the regression lines between small, medium, and large CNV were
      significant (p<0.001). The slope of the regressions lines was significant except
      for small CNV. Regarding the 10 degrees field (Humphrey), there were no
      statistical differences in the slope of the regression lines (p=0.867).
      CONCLUSIONS: Transpupillary thermotherapy with small CNV did not show a
      statistically significant decrease of VA. Thus, in clinical terms early treatment
      of occult CNV with TTT seems to be able to prevent a further loss of visual
      acuity.

PMID- 15744491
TI  - Professor von Mikulicz-Radecki, Breslau: 100 years since his death.

PMID- 15744492
TI  - Assessment of ploidy stability of the somatic embryogenesis process in Quercus
      suber L. using flow cytometry.
AB  - Flow cytometry analyses were used to verify the ploidy stability of Quercus suber
      L. somatic embryogenesis process. Leaf explants of two adult cork oak trees (QsG0
      and QsG5) of the North of Portugal were inoculated on MS medium with 2,4-D and
      zeatin. After 3 months, calluses with embryogenic structures were isolated and
      transferred to fresh MS medium without growth regulators and somatic embryo
      evolution was followed. Morphologically normal somatic embryos (with two
      cotyledons) and abnormal somatic embryos (with one or three cotyledons) were used
      in this assay. Flow cytometry combined with propidium iodide staining was
      employed to estimate DNA ploidy levels and nuclear DNA content of somatic embryos
      and leaves from mother plants. No significant differences (P< or =0.05) were
      detected among embryos, and between the embryos and the mother plants. Also,
      after conversion of these embryos, no significant morphological differences were
      observed among the somatic embryo-derived plants. These results and further
      studies using converted plantlet leaves and embryogenic callus tissue indicate
      that embryo cultures and converted plantlets were stable with regard to ploidy
      level. As no major somaclonal variation was detected our primary goal of "true-to
      type" propagation of cork oak using somatic embryogenesis was assured at this
      level. The estimation of the 2C nuclear DNA content for this species is similar
      to the previously obtained value.

PMID- 15744493
TI  - Late type of daughter cell wall synthesis in one of the Chlorellaceae,
      Parachlorella kessleri (Chlorophyta, Trebouxiophyceae).
AB  - Autosporulation is a common mode of propagation for unicellular algae. Autospore
      forming species of Chlorellaceae, Chlorella vulgaris Beijerinck, C. sorokiniana
      Shihira et Krauss, C. lobophora Andreyeva, and Parachlorella kessleri (Fott et
      Novakova) Krienitz et al. have glucosamine as the main constituent of their rigid
      cell wall. Recent phylogenetic analyses have showed that the Chlorellaceae
      divided into two sister groups: the Chlorella-clade and the Parachlorella-clade.
      We compared the cell wall structure and synthesis of the daughter cell wall in
      the four species by electron microscopy using rapid freezing and freeze
      substitution methods. The cell wall of C. vulgaris, C. sorokiniana, and C.
      lobophora consisted of an electron-dense thin layer with an average thickness of
      17-20, 22, and 19 nm, respectively. In these three species, daughter cell wall
      synthesis occurred on the outer surface of the plasma membrane in the early cell
      growth phase. The cell wall of P. kessleri, however, was electron-transparent and
      54-59 nm in thickness. Ruthenium red staining of P. kessleri indicated that
      ruthenium-red-specific polysaccharides accumulated over the outer surface of the
      plasma membrane. Immunoelectron microscopic observation with an anti-beta-1, 3
      glucan antibody and staining with wheat germ agglutinin (WGA) indicated that the
      cell wall contained beta-1, 3-glucan and WGA specific N-acetyl-beta-D
      glucosamine. In P. kessleri, daughter cell wall synthesis began after successive
      protoplast division. The daughter cell wall synthesis during autosporulation in
      the four species of Chlorellaceae can be classified into two types-the early and
      the late types.

PMID- 15744494
TI  - Antisense reduction of thylakoidal ascorbate peroxidase in Arabidopsis enhances
      paraquat-induced photooxidative stress and nitric oxide-induced cell death.
AB  - The production and characterization of Arabidopsis plants containing a transgene
      in which the Arabidopsis tAPX is inserted in antisense orientation, is described.
      tAPX activity in these transgenic tAPX plants is around 50% of control level. The
      tAPX antisense plants are phenotypically indistinguishable from control plants
      under normal growth conditions; they show, however, enhanced sensitivity to the
      O2- -generating herbicide, Paraquat. Interestingly, the tAPX antisense plants
      show enhanced symptoms of damage when cell death is triggered through treatment
      with the nitric oxide-donor, SNP. These results are in accordance with the ones
      recently obtained with transgenic plants overexpressing tAPX; altogether, they
      suggest that tAPX, besides the known ROS scavenging role, is also involved in the
      fine changes of H2O2 concentration during signaling events.

PMID- 15744495
TI  - Elevated tyrosine decarboxylase and tyramine hydroxycinnamoyltransferase levels
      increase wound-induced tyramine-derived hydroxycinnamic acid amide accumulation
      in transgenic tobacco leaves.
AB  - Feruloyltyramine (FT) and 4-coumaroyltyramine (4CT) participate in the defense of
      plants against pathogens through their extracellular peroxidative polymerization,
      which is thought to reduce cell wall digestibility. Hydroxycinnamoyl-CoA:tyramine
      N-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110) and tyrosine decarboxylase
      (TYDC; EC 4.1.1.25) are purported to play key roles in the stress-induced
      regulation of tyramine-derived hydroxycinnamic acid amide (HCAAT) metabolism.
      Transgenic tobacco (Nicotiana tabacum cv. Xanthi) was engineered to
      constitutively express tobacco THT. A T1 plant over-expressing THT was crossbred
      with T1 tobacco expressing opium poppy TYDC2, to produce a T2 line with elevated
      THT and TYDC activities compared with wild type plants. The effects of an
      independent increase in TYDC or THT activity, or a dual increase in both TYDC and
      THT on the cellular pools of HCAAT pathway intermediates and the accumulation of
      soluble and cell wall-bound FT and 4CT were examined. Increased TYDC activity
      resulted in a larger cellular pool of tyramine and lower levels of L
      phenylalanine in transgenic leaves. In contrast, elevated THT activity reduced
      tyramine levels. HCAAT levels were low in healthy leaves, but were induced in
      response to wounding and accumulated around wound sites. Similarly, endogenous
      THT and TYDC activities were wound-induced. The rate of wound-induced HCAAT
      accumulation was highest in transgenic plants with elevated THT and TYDC
      activities showing that both enzymes exert control over the flux of intermediates
      involved in HCAAT biosynthesis under some conditions.

PMID- 15744497
TI  - Molecular cloning of a new cDNA and expression of 3-hydroxy-3-methylglutaryl-CoA
      synthase gene from Hevea brasiliensis.
AB  - 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS), EC 4.1.3.5, is an essential
      enzyme in rubber biosynthesis in Hevea brasiliensis. We have isolated a new cDNA
      encoding HMGS in H. brasiliensis. The full-length hmgs2 consists of 1,916-bp and
      encodes a protein of 464 amino acids with a predicted molecular mass of 51.27 kDa
      and an isoelectric point of 6.02. In comparison, HMGS1 and HMGS2 show 92% and 94%
      nucleotide and amino acid sequence identities, respectively. Semiquantitative RT
      PCR analysis indicates that the hmgs2 is more highly expressed in laticifer and
      petiole than in leaves. Sequence searching and alignment revealed that HMGS is a
      distant relative of the condensing enzyme; beta-ketoacyl acyl carrier protein
      synthase III (ACP synthase III), EC 2.3.1.41, identified three completely
      conserved residues; Cys(117), His(247), and Asn(326). The relationship was
      greatly strengthened by making a proper alignment of numerous sequences of both
      HMGS and ACP synthase III. The same Cys(117), His(247), and Asn(326) absolutely
      conserved in both groups play a catalytic role in ACP synthase III, while such a
      role of Cys and His has only been reported for HMGS. According to site-directed
      mutagenesis, the expressed wild-type enzyme shows comparable level with mutant
      proteins. The mutation of Cys(117) and Asn(326) affects the HMGS activity,
      indicating that Cys(117) and Asn(326) are important amino acids for the catalytic
      activity of HMGS. A phylogenetic tree constructed on the basis of proper multiple
      alignment indicates that HMGS1 and HMGS2 result from recent gene duplication.
      This is also the case for HMGS and ACP synthase III, which appear to have arisen
      from an ancient gene duplication event of an ancestral condensing enzyme.
      Therefore, a possible secondary structure of HMGS could be predicted based on the
      Protein Data Bank information of ACP synthase III.

PMID- 15744496
TI  - Profiling of diurnal patterns of metabolite and transcript abundance in potato
      (Solanum tuberosum) leaves.
AB  - Diurnal changes in carbohydrates and a broad range of primary metabolites were
      analysed through a diurnal period in potato leaves (Solanum tuberosum cv.
      Desiree) using an established gas chromatography-mass spectrometry based
      metabolic profiling protocol alongside conventional spectrophotometric
      technologies. In tandem, we profiled transcript levels using both a custom array
      containing approximately 2,500 cDNA clones predominantly representing transcripts
      involved in primary metabolism and commercially available arrays containing
      approximately 12,000 cDNA clones that gave coverage of transcript levels over a
      broader functional range. The levels of many metabolites and transcripts varied
      during the diurnal period with 56 significant differences observed in the
      metabolite contents and 832 significant differences recorded in transcript
      levels. Whilst a large number of the differences would be expected from what has
      been known previously, several novel changes were observed in these experiments.
      Notably, qualitative comparison of the combined data sets obtained from the
      parallel analysis of transcripts and metabolites suggests relatively few changes
      in gene expression strongly correlate with changes in metabolite levels during a
      diurnal cycle. Furthermore, these changes appear to be confined to the central
      metabolic pathways. However, principal component analysis of the metabolic
      profiles obtained here revealed that metabolite patterns change progressively
      through a diurnal period suggesting the operation of mechanisms for tight
      temporal regulation of metabolite composition.

PMID- 15744498
TI  - An unusual presentation of Helicobacter pylori infection: so-called "Russell body
      gastritis".
AB  - Helicobacter pylori (H. pylori) is a "slow" bacterial pathogen, which induces
      several gastroduodenal diseases. Varying degrees of inflammation can be present
      in the gastric mucosa of patients infected with H. pylori. The case presented
      here is a male patient suffering from dyspepsia and nausea. His upper
      gastrointestinal endoscopy revealed pan gastritis. Histological examination of
      multiple gastric biopsies taken from the body and antrum showed a rare
      morphological expression of H. pylori gastritis characterized by diffuse plasma
      cell infiltration with extensive Russell body formation. Diffuse infiltration of
      plasma cells with Russell bodies in gastric mucosa can cause difficulties in
      differentiation from neoplastic processes. However, immunohistochemically, the
      infiltrating cells in the gastric mucosa stained negatively with cytokeratins
      while they expressed both kappa and lambda light chains showing their polyclonal
      nature. The presence of diffuse plasma cells with Russell bodies in the gastric
      mucosa may represent a different presentation of H. pylori gastritis. There are
      only two case reports of similar presentation and both have been called "Russell
      body gastritis".

PMID- 15744499
TI  - The use of Bcl-2 and PTHLH immunohistochemistry in the diagnosis of peripheral
      chondrosarcoma in a clinicopathological setting.
AB  - Distinguishing osteochondroma from low-grade secondary peripheral chondrosarcoma
      can be difficult. In osteochondroma, growth-signalling pathways are thought to be
      downregulated through exostosin (EXT) inactivation. A previous pilot study
      focusing on expression of putative EXT downstream effectors indicated that
      progression of osteochondroma towards grade I chondrosarcoma was characterised by
      upregulation of Bcl-2 and parathyroid hormone-like hormone (PTHLH). We
      investigated their use as diagnostic markers in a large nationwide series of 71
      osteochondromas and 34 chondrosarcomas. Bcl-2 immunohistochemistry proved to be a
      valuable diagnostic tool: scoring negative in 95% (specificity) of the
      osteochondromas and positive in 57% (sensitivity) of the chondrosarcomas,
      reaching a positive predictive value of 84% and negative predictive value of 82%.
      Positivity was not related to age, hereditary status, gender or thickness of the
      cartilage cap. Presence of internal controls and verification using mRNA in situ
      hybridisation strengthened the reliability of the immunohistochemical staining.
      PTHLH showed more variable staining, being positive in osteochondromas from
      females or adolescent males, suggesting age- and gender-dependent expression.
      Thus, in cases where the distinction between osteochondroma and chondrosarcoma is
      difficult, Bcl-2 is a valuable diagnostic marker for malignancy, regardless of
      tumour size, patient gender or age, and this can be extended with PTHLH for non
      adolescent male patients.

PMID- 15744500
TI  - Chloroplast DNA base substitutions: an experimental assessment.
AB  - An experimental assessment was carried out to determine directly the frequency
      and types of spontaneous base substitutions that occur in chloroplast DNA. A
      target site within the chloroplast 16S rRNA gene of the green alga Chlamydomonas
      reinhardtii was chosen for the assay. Mutations at this site were known to confer
      spectinomycin resistance and simultaneously result in the loss of an AatII
      cleavage site. In the experiments reported here, base substitutions at any
      individual base occurred at a frequency in the range of 0.9-11 per 10(9) viable
      cells plated. Four new mutations that confer resistance to spectinomycin were
      identified at the target site in the Chlamydomonas chloroplast 16S rRNA gene.
      When the relative rates of transition and transversion mutations were quantified,
      a bias toward transversions was observed. The prominence of A/T --> C/G
      transversions in the observed mutation spectrum suggests that oxidative damage
      may be the major cause of base substitution mutations within the chloroplast.

PMID- 15744501
TI  - Rearrangements of large-insert T-DNAs in transgenic rice.
AB  - Introduction of large-DNA fragments into cereals by Agrobacterium-mediated
      transformation is a useful technique for map-based cloning and molecular
      breeding. However, little is known about the organization and stability of large
      fragments of foreign DNA introduced into plant genomes. In this study, we
      produced transgenic rice plants by Agrobacterium-mediated transformation with a
      large-insert T-DNA containing a 92-kb region of the wheat genome. The structures
      of the T-DNA in four independent transgenic lines were visualized by fluorescence
      in situ hybridization on extended DNA fibers (fiber FISH). By using this
      cytogenetic technique, we showed that rearrangements of the large-insert T-DNA,
      involving duplication, deletion and insertion, had occurred in all four lines.
      Deletion of long stretches of the large-insert DNA was also observed in
      Agrobacterium.

PMID- 15744503
TI  - Energy-efficient recovery of butanol from model solutions and fermentation broth
      by adsorption.
AB  - This article discusses the separation of butanol from aqueous solutions and/or
      fermentation broth by adsorption. Butanol fermentation is also known as acetone
      butanol ethanol (ABE) or solvent fermentation. Adsorbents such as silicalite,
      resins (XAD-2, XAD-4, XAD-7, XAD-8, XAD-16), bone charcoal, activated charcoal,
      bonopore, and polyvinylpyridine have been studied. Use of silicalite appears to
      be the more attractive as it can be used to concentrate butanol from dilute
      solutions (5 to 790-810 g L(-1)) and results in complete desorption of butanol
      (or ABE). In addition, silicalite can be regenerated by heat treatment. The
      energy requirement for butanol recovery by adsorption-desorption processes has
      been calculated to be 1,948 kcal kg(-1) butanol as compared to 5,789 kcal kg(-1)
      butanol by steam stripping distillation. Other techniques such as gas stripping
      and pervaporation require 5,220 and 3,295 kcal kg(-1) butanol, respectively.

PMID- 15744502
TI  - Characterization of a mitochondrially targeted single-stranded DNA-binding
      protein in Arabidopsis thaliana.
AB  - A gene encoding a predicted mitochondrially targeted single-stranded DNA binding
      protein (mtSSB) was identified in the Arabidopsis thaliana genome sequence. This
      gene (At4g11060) codes for a protein of 201 amino acids, including a 28-residue
      putative mitochondrial targeting transit peptide. Protein sequence alignment
      shows high similarity between the mtSSB protein and single-stranded DNA binding
      proteins (SSB) from bacteria, including residues conserved for SSB function.
      Phylogenetic analysis indicates a close relationship between this protein and
      other mitochondrially targeted SSB proteins. The predicted targeting sequence was
      fused with the GFP coding region, and the organellar localization of the
      expressed fusion protein was determined. Specific targeting to mitochondria was
      observed in in-vitro import experiments and by transient expression of a GFP
      fusion construct in Arabidopsis leaves after microprojectile bombardment. The
      mature mtSSB coding region was overexpressed in Escherichia coli and the protein
      was purified for biochemical characterization. The purified protein binds single
      stranded, but not double-stranded, DNA. MtSSB stimulates the homologous strand
      exchange activity of E. coli RecA. These results indicate that mtSSB is a
      functional homologue of the E. coli SSB, and that it may play a role in
      mitochondrial DNA recombination.

PMID- 15744504
TI  - Rheology and hydrodynamic properties of Tolypocladium inflatum fermentation broth
      and its simulation.
AB  - A physico-chemical, two phase simulated pseudoplastic fermentation (SPF) broth
      was investigated in which Solka Floc cellulose fibre was used to simulate the
      filamentous biomass, and a mixture of 0.1% (w/v) carboxymethyl cellulose (CMC)
      and 0.15 M aqueous sodium chloride was used to simulate the liquid fraction of
      the fermentation broth. An investigation of the rheological behaviour and
      hydrodynamic properties of the SPF broth was carried out, and compared to both a
      fungal Tolypocladium inflatum fermentation broth and a CMC solution in a 50 L
      stirred tank bioreactor equipped with conventional Rushton turbines. The
      experimental data confirmed the ability of the two phase SPF broth to mimic both
      the T. inflatum broth bulk rheology as well as the mixing and mass transfer
      behaviour. In contrast, using a homogeneous CMC solution with a similar bulk
      rheology to simulate the fermentation resulted in a significant underestimation
      of the mass transfer and mixing times. The presence of the solid phase and its
      microstructure in the SPF broth appear to play a significant role in gas holdup
      and bubble size, thus leading to the different behaviours. The SPF broth seems to
      be a more accurate simulation fluid that can be used to predict the bioreactor
      mixing and mass transfer performance in filamentous fermentations, in comparison
      with CMC solutions used in some previous studies.

PMID- 15744505
TI  - Morphological and molecular diversity and abundance of tomentelloid
      ectomycorrhizae in broad-leaved forests of the Hungarian Plain.
AB  - The most common representatives of tomentelloid ectomycorrhizae (EM) collected in
      broad-leaved forests (Populus and Quercus) of the Hungarian Plain during a 4-year
      project are demonstrated. Eighteen specimens of nine tomentelloid EM morphotypes
      were investigated. Five of these, introduced here for the first time, were
      characterized by microscopical-morphological and anatomical methods. Molecular
      identification was carried out using sequence analysis of the nrDNA ITS region.
      Altogether, 54 ITS sequences (6 previously published and 12 new sequences from
      our mycorrhizae and 36 from GenBank derived from fruitbodies) were compared by
      phylogenetic analyses using neighbor-joining, maximum parsimony and maximum
      likelihood methods. Identification to species level was successful in the case of
      six EM morphotypes (Tomentella galzinii, T. subtestacea, T. sublilacina, T.
      pilosa, T. ferruginea and T. stuposa), and the possible taxonomic position of the
      remaining three was approached. These results are supported by morphology, as
      compared with literature data. Relative abundance of the EM morphotypes within
      the soil samples was estimated. Our results confirm that tomentelloid EM are
      constant, diverse and abundant members of the EM communities in temperate
      continental broad-leaved forests.

PMID- 15744506
TI  - Prototropic tautomerism of imidazolone in aqueous solution: a density functional
      approach using the combined discrete/self-consistent reaction field (SCRF)
      models.
AB  - A systematic investigation of the proton transfer in the keto-amino/enol
      tautomerization of imidazolone was undertaken. Calculations in aqueous solution
      were performed using both combined discrete/self-consistent reaction field (SCRF)
      and SCRF methods. Complexes containing one to three water molecules around the
      hydrophilic site of imidazolone were used for the combined discrete/SCRF
      calculations. The DFT results predict that the barrier height for non-water
      assisted intramolecular proton transfer is very high (214.8 kJmol(-1)). Hydrogen
      bonding between imidazolone and the water molecule(s) will dramatically lower the
      barrier by a concerted multiple proton transfer mechanism. The proton transfer
      process through a eight-member ring formed by imidazolone and two water molecules
      is found to be more efficient and the calculated barrier height is ca. 61 kJmol(
      1).

PMID- 15744507
TI  - Post-choice information processing by pigeons.
AB  - In a conditional discrimination (matching-to-sample), a sample is followed by two
      comparison stimuli, one of which is correct, depending on the sample. Evidence
      from previous research suggests that if the stimulus display is maintained
      following an incorrect response (the so-called penalty-time procedure),
      acquisition by pigeons is facilitated. The present research tested the hypothesis
      that the penalty-time procedure allows the pigeons to review and learn from the
      maintained stimulus display following an incorrect choice. It did so by including
      a penalty-time group for which, following an incorrect choice, the sample changed
      to match the incorrect comparison, thus providing the pigeons with post-choice
      'misinformation.' This misinformation group acquired the matching task
      significantly slower than the standard penalty-time group (that had no change in
      the sample following an error). Furthermore, acquisition of matching by a control
      group that received no penalty time fell midway between the other two groups,
      suggesting that the pigeons did not merely take more care in making choices
      because of the aversiveness of penalty-time. Thus, it appears that in the
      acquisition of matching-to-sample, when the stimulus display is maintained
      following an incorrect choice, the pigeons can review or acquire information from
      the display. This is the first time that such an effect has been reported for a
      nonhuman species.

PMID- 15744509
TI  - Transtympanic corticoid therapy for acute profound hearing loss.
AB  - The prognosis of idiopathic sudden hearing loss depends on its severity; acute
      complete deafness, for example, has a particularly bad prognosis. The treatment
      of acute deafness is based on a systemic application of corticosteroids.
      Corticoid concentrations in the cochlea are higher after transtympanic
      application in comparison to systemic application. We therefore investigated
      whether an additional transtympanic corticoid therapy gives an advantage over
      systemic standard therapy. We report on 27 patients with sudden idiopathic
      profound hearing loss or deafness who were treated in the Department of
      Otorhinolaryngology, University of Essen, Germany. Fourteen patients were treated
      with a rheologic infusion therapy with systemic prednisolone. Thirteen patients
      were treated additionally with methylprednisolone (Urbason) transtympanically
      through a ventilation tube. In the first group of patients who were treated with
      infusion therapy and corticoids systemically, three patients had good recovery of
      hearing. Another five patients had a partial recovery of hearing. The average
      hearing gain from 0.5-4 kHz was 15 dB. In the group of patients who were treated
      additionally with local corticoids, two patients reported a good recovery of
      hearing and another two patients only had a partial recovery of hearing. The
      average hearing gain in the above-mentioned frequency range was 11 dB. In our
      patients the additional transtympanic application of corticoids did not result in
      a significantly improved recovery of hearing in comparison to the patients
      treated with the standard therapy alone.

PMID- 15744508
TI  - Evaluation of serum dioxin congeners among residents near continuously burning
      municipal solid waste incinerators in Korea.
AB  - The objective of this study was to evaluate the congeners of polychlorinated
      dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in Korean
      serum samples as biological markers. Serum samples from 103 participants were
      analyzed. Participants consisted of 28 workers in municipal solid waste
      incinerators (MSWIs), and 21 men and 54 women who had lived for at least 3 years
      prior to 2002 in areas within 300 m of incinerators in large Korean cities. Serum
      samples were analyzed for 17 PCDD/PCDFs congeners by high resolution gas
      chromatography-high resolution mass spectrometry. Geometric mean (GM) PCDD/PCDF
      levels in the serum samples were 3.14, 8.04, 6.12 and 6.60 pg TEQ/g lipid for
      workers, male residents, female residents and the sum of male and female
      residents, respectively. The GM PCDD/PCDF level in the serum of workers was not
      significantly different from the values for residents near MSWIs. In the 75
      participants who resided near MSWIs, the congeners that most contributed to the
      total TEQ were 1,2,3,6,7,8-hexachlorodibenzofuran (1,6-HxCDF), 2,3,4,7,8
      pentachlorodibenzofuran (4-PeCDF), 1,2,3,4,6,7,8-heptachlorodibenzofuran (1,4,6
      HpCDF), 1,2,3,7,8,9-hexachlorodibenzofuran (1,9-HxCDF), 1,2,3,4,7,8
      hexachlorodibenzo-p-dioxin (1,4-HxCDD), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin
      (1,6-HxCDD). In the workers, the congeners that made the greatest contribution
      were 1,6-HxCDD, 4-PeCDF, 1,2,3,4,6,7,8-heptachlorodibenzop-dioxin (HpCDD), and
      1,6-HxCDF. In conclusion, the serum TEQ levels for PCDD/PCDFs in the incinerator
      workers and residents near the MSWIs in Korea were lower than those reported for
      other countries. Comparison of the PCDD/PCDF levels of workers at MSWIs and
      nearby residents revealed no significant enhancement of PCDD/PCDF exposure in
      workers. PCDD/PCDF intake from animal origin was assumed to be lower than that of
      Europeans. Further studies of Korean foods are needed to clarify the exposure
      route for PCDD/PCDFs in the Korean population.

PMID- 15744510
TI  - Pharyngeal morphology in children with submucous cleft palate with and without
      surgery.
AB  - Seventy-three children with submucous cleft palate (34 girls and 39 boys) with a
      mean age of 6.2 years (range 5.5-7.5) were compared retrospectively from lateral
      cephalograms. Thirty of the patients were not operated on, while 43 had had
      either palatal closure (n = 13, mean age at operation: 1.7 years, range 0.8-3.9)
      or velopharyngeal flap (VPP) surgery (n = 30, mean age at operation 3.7 years,
      range 1-6.8). There were no significant differences in the pharyngeal dimensions
      between girls and boys or patients without surgery and with palatal repair.
      Patients who had had VPP had the largest sagittal depths of the nasopharyngeal
      airway and smallest sagittal depths of the oropharyngeal airway. VPP in childhood
      was associated with narrowing of the lower pharyngeal airway.

PMID- 15744511
TI  - Microscopic thyroidectomy: a prospective controlled trial.
AB  - The purpose of this prospective study was to evaluate microsurgical thyroidectomy
      by comparing it with traditional thyroidectomy. Before surgery, patients were
      assigned either to the microscopic thyroidectomy group (MT group), with the use
      of the surgical microscope, or the traditional thyroidectomy group (TT group),
      without the use of visual magnification. Outcome measures were operative time,
      intraoperative bleeding and complication rates including injury to the recurrent
      laryngeal nerve (RLN), the external branch of the superior laryngeal nerve
      (EBSLN) or the parathyroid glands. Ninety-eight patients underwent thyroid
      surgery (58 patients in the MT group, 40 patients in the TT group). The two
      groups were similar in age, sex, surgical procedures and histological findings.
      There was no difference between the two techniques regarding the operative time
      and the amount of blood loss. Neither permanent nerve palsy nor persistent
      hypocalcemia occurred in either group. Transient nerve palsies (RLN and EBSLN)
      were lower in the MT group (1.7%) compared to the TT group (7.5%), but the
      difference did not reach statistical significance (P>0.05). Overall transient
      hypocalcemia was significantly lower in the MT group (1.7%) compared with the TT
      group (12.5%, P=0.032). If the population was restricted to total thyroidectomy,
      the rate of transient hypocalcemia was 4.1% in the MT group and 33.3% in the TT
      group, respectively (P=0.022). In conclusion, microsurgical thyroidectomy is a
      feasible and efficacious surgical procedure. It significantly reduces the
      complications without increasing the operating time in thyroid surgery
      procedures. A major advantage of this technique is the possibility of attaching a
      camera to the microscope, thereby greatly facilitating teaching.

PMID- 15744512
TI  - [Early diagnosis of liver diseases].
AB  - In Germany, liver diseases are the leading cause of death through illness among
      30 to 45 year olds. Most are chronic diseases and timely preventative or
      therapeutic measures could avert their manifestation or at least the following
      complications. Currently, screening for liver diseases is focused on specific
      groups at risk such as patients with alcohol abuse, relatives of patients with a
      genetic disease or individuals at risk of an infection with a viral hepatitis.
      For some diseases, studies have been started to test the practicability of
      population screening, which has already been successfully implemented for
      Hepatitis B and C in blood donors. Screening is also recommended for advanced
      liver disease. It helps to detect the development of cirrhosis and its
      complications namely varices and hepatocellular carcinoma.

PMID- 15744513
TI  - Combination of gravitational SPLITT fractionation and field-flow fractionation
      for size-sorting and characterization of sea sediment.
AB  - A combination of gravitational split-flow thin (SPLITT) fractionation and
      sedimentation/steric field-flow fractionation (Sd/StFFF) has been used for
      continuous size-sorting of a sediment sample and for size analysis of the
      collected fractions. An IAEA (International Atomic Energy Agency) sediment
      material was separated into four size fractions (with theoretical size ranges
      <1.0, 1.0-3.0, 3.0-5.0, and >5.0 microm in diameter) by means of a three-step
      gravitational SPLITT fractionation (GSF) for which the same GSF channel was used
      throughout. The GSF fractions were collected and examined by optical microscopy
      (OM) and by Sd/St FFF. The mean diameters of the GSF fractions measured by OM
      were within the size interval predicted by GSF theory, despite the theory
      assuming that all particles are spherical, which is not true for the sediment
      particles. The Sd/St FFF results showed that retention shifted toward shorter
      elution time (or larger size) than expected, probably because of the shape
      effect. The results from GSF, OM, and Sd/StFFF are discussed in detail.

PMID- 15744514
TI  - Development of an analytical procedure for determination of selected estrogens
      and progestagens in water samples.
AB  - An analytical procedure has been developed for determination of eight selected
      natural and synthetic hormonal steroids in surface water and in effluent samples.
      Several methodological points have been investigated and are discussed; they
      include the choice of the solid-phase extraction sorbent, the influence of flow
      rate on recovery, the breakthrough volume for a given sorbent (Env+ and Oasis
      HLB), sample clean up, and sample storage. As regards the latter point, it was
      found that when no preservative was added to effluent from a sewage-treatment
      plant, severe loss of steroids occurred-85% of progesterone and about 30% of both
      estrone and estradiol were found to be degraded in 24 h. The procedure developed
      was applied to samples from the Seine river estuary. Sex steroids were not
      detected in surface water; estrone was the most commonly detected steroid in
      sewage-treatment plant effluent, with levels ranging from 1.8 to 8.3 ng L(-1).
      Synthetic estrogens (ethynylestradiol and mestranol) and progestagens
      (levonorgestrel and norethindrone) were never detected, whatever the sampling
      season. Overall, for 162 out of 168 measurements levels were below the detection
      limits of the developed procedure.

PMID- 15744515
TI  - Fluorescence analysis of humic and fulvic acids from two Brazilian oxisols as
      affected by biosolid amendment.
AB  - Conventional monodimensional fluorescence spectroscopy in the emission,
      excitation, and synchronous-scan modes and total luminescence spectroscopy have
      proven to be sensitive techniques for characterization and differentiation of
      humic acid (HA) and fulvic acid (FA) fractions isolated from an aerobically and
      anaerobically digested and limed biosolid, two layers of a sandy and a clayey
      Brazilian oxisol, and the corresponding biosolid-amended soils. The spectral
      patterns and the relative fluorescence intensities suggest greater molecular
      heterogeneity, less aromatic polycondensation, and less humification of biosolid
      HA and FA compared with soil HA and FA. However, the differences are smaller for
      the FA fractions than for the HA fractions. Fluorescence properties of soil HA
      and FA differ slightly as a function of soil type and soil layer. Biosolid
      application causes a shift to shorter wavelengths of the main fluorescence peaks
      and marked variation of the relative fluorescence intensities of HA and FA
      isolated from amended soils. These results suggest that molecular components of
      relatively small molecular size, with a low level of aromatic polycondensation,
      and low degree of humification present in biosolid HA and FA are partially and
      variously incorporated into amended soil HA and FA. In general, these
      modifications seem to be smaller in HA and FA from the clayey soil layers than in
      those from the sandy soil layers, possibly because of protective effects exerted
      by clay minerals of native soil HA and FA against disturbances caused by biosolid
      application.

PMID- 15744516
TI  - Ultrasonic extraction followed by sulfuric acid silica gel cleanup for the
      determination of alpha-hexachlorocyclohexane enantiomers in biota samples.
AB  - Interest in the analysis of alpha-hexachlorocyclohexane (alpha-HCH) enantiomers
      as an alternative or complementary approach to elucidating isomer ratios of
      alpha/gamma-HCH has grown in recent years because it can provide useful
      information to evaluate the influence of different degradation and transformation
      processes. In this paper, a simple and rapid method for the determination of
      alpha-HCH enantiomers in biota samples is described. The method developed
      consists of ultrasonic extraction, sulfuric acid silica gel cleanup, solid-phase
      extraction (SPE) column fractionation, and final determination with chiral high
      resolution gas chromatography. Ultrasonic extraction greatly shortens the
      extraction process time, and the sulfuric acid silica gel and SPE cleanup
      perfectly remove lipids and other interference compounds in the lipid-rich
      samples. The method is found to be simple, less time-consuming, and easy to
      operate, thus providing a useful alternative method to assess the
      enantioselective breakdown of alpha-HCH in biota system.

PMID- 15744517
TI  - Optical detection and discrimination of cystic fibrosis-related genetic mutations
      using oligonucleotide-nanoparticle conjugates.
AB  - Novel methods for application of oligonucleotide-gold nanoparticle conjugates to
      selective colorimetric detection and discrimination of cystic fibrosis (CF)
      related genetic mutations in model oligonucleotide systems are presented. Three
      strand oligonucleotide complexes are employed, wherein two probe oligonucleotide
      gold nanoparticle conjugates are linked together by a third target
      oligonucleotide strand bearing the CF-related mutation(s). By monitoring the
      temperature dependence of the optical properties of the complexes, either in
      solution or on silica gel plates, melting behaviors may be accurately and
      reproducibly compared. Using this approach, fully complementary sequences are
      successfully distinguished from mismatched sequences, with single base mismatch
      resolution, for Delta F 508, M470V, R74W and R75Q mutations.

PMID- 15744518
TI  - Application of an SPR-based receptor assay for the determination of biologically
      active recombinant bone morphogenetic protein-2.
AB  - Human bone morphogenetic protein-2 (hBMP-2) is a member of the human transforming
      growth factor-beta superfamily. Biologically active bone morphogenetic protein-2
      (BMP-2) is a dimeric protein that binds in the first step of the signal
      transduction cascade to specific receptors on the cell-surface. This specific
      interaction of the dimeric protein with the extracellular ligand-binding domain
      (ECD) of the receptor was used to develop a receptor-based assay based on an
      optical biosensor system (Biacore 2000, Biacore AB, Uppsala, Sweden). The ECD of
      the BMP-receptor type IA, tagged with the Fc part of IgG (BMPR-IA-Fc), was
      immobilised on the surface of a dextran-protein A-coated sensor chip. Calibration
      curves were obtained with purified and biologically active recombinant hBMP-2
      (rhBMP-2) that showed a linear range from approximately 5 to 250 nM rhBMP-2.
      Moreover, this assay was used to quantitatively follow the generation of
      biologically active protein during the renaturation from unfolded and reduced
      monomers to biologically active dimers. A refolding mixture containing renatured
      dimeric rhBMP-2 and not correctly folded monomers, was used as the sample
      solution without any further pre-treatment. It was proven that only the
      biologically active dimers were recognised by the immobilised receptor, so the
      generation of biologically active rhBMP-2 during the renaturation process could
      be monitored directly and rapidly. Furthermore, the results from the optical
      sensor obtained during the renaturation process showed a good correlation with
      the data obtained by non-reducing SDS-PAGE analysis carried out at the end of the
      renaturation process. These data show that the disulphide-bonded dimer
      corresponds to the biologically active protein capable of binding the BMP
      receptor type IA.

PMID- 15744519
TI  - Determination of thiol by high-performance liquid chromatography and fluorescence
      detection with 5-methyl-(2-(m-iodoacetylaminophenyl)benzoxazole.
AB  - A new high-performance liquid chromatographic (HPLC) method for measuring low
      molecular weight (LMW) thiol-containing compounds, including cysteine (CysH),
      glutathione (GSH), N-acetylcysteine (Nac), penicillamine (PA), and 2
      mercaptoethanol (2-ME), has been developed by using 5-methyl-(2-(m
      iodoacetylaminophenyl)benzoxazole (MIPBO) as fluorescence-labeling reagent. The
      derivatization and separation conditions have been investigated in detail.
      Detection limits ranging from 3.5 to 15.0 fmol were achieved for the thiols
      investigated in a 16 min separation with detection wavelengths 310 and 375 nm for
      the excitation and emission, respectively. The utility of the proposed method has
      been validated by measuring CysH in human urine samples.

PMID- 15744520
TI  - Rapid genotyping for most common TGFBI mutations with real-time polymerase chain
      reaction.
AB  - Recent studies of the corneal dystrophies (CDs) have shown that most cases of
      granular CD, Avellino CD, and lattice CD type I are caused by mutations in the
      human transforming growth factor beta-induced (TGFBI) gene. The aim of this study
      was to develop a rapid diagnostic assay to detect mutations in the TGFBI gene.
      Sixty-six patients from 64 families with TGFBI-associated CD were studied. A
      primer probe set was designed to examine the genome from exons 4 and 12 of the
      TGFBI gene in order to identify mutant and wild-type alleles. A region spanning
      the mutations was amplified by the polymerase chain reaction (PCR) in a
      commercial cycler. Mutations were then identified by melting curve analysis of
      the hybrid formed between the PCR product and a specific fluorescent probe. Using
      this system, we clearly distinguished each CD genotype (homozygous and
      heterozygous 418G-->A, heterozygous 417C-->T, heterozygous 1710C-->T, and wild
      type) of all the patients by means of the clearly distinct melting peaks at
      different temperatures. One thermal cycling took approximately 54 min, and all
      results were completely in concordance with the genotypes determined by
      conventional DNA sequencing. Thus, the technique is accurate and can be used for
      routine clinical diagnosis. We expect that our new method will help in making
      precise diagnoses of patients with atypical CDs and aid the revision of the
      clinical classification of inherited corneal diseases based on the genetic
      pathogenesis.

PMID- 15744521
TI  - FISH analysis of hematological neoplasias with 1p36 rearrangements allows the
      definition of a cluster of 2.5 Mb included in the minimal region deleted in 1p36
      deletion syndrome.
AB  - Rearrangements in the distal region of the short arm of chromosome 1 are
      recurrent aberrations in a broad spectrum of human neoplasias. However, neither
      the location of the breakpoints (BP) on 1p36 nor the candidate genes have been
      fully determined. We have characterized, by fluorescence in situ hybridization
      (FISH), the BP in 26 patients with hematological neoplasias and 1p36
      rearrangements in the G-banding karyotype. FISH allowed a better characterization
      of all samples analyzed. Nine cases (35%) showed reciprocal translocations, 15
      (58%) unbalanced rearrangements, and two (7%) deletions. We describe two new
      recurrent aberrations. In 18 of the 26 cases analyzed the BP were located in band
      1p36, which is 25.5 Mb long. In 14 of these 18 cases (78%) and without
      distinction between myeloid and lymphoid neoplasias, the BP clustered in a 2.5 Mb
      region located between 1p36.32 and the telomere. Interestingly, this region is
      contained in the 10.5 Mb cluster on 1p36.22-1pter defined in cases with 1p36
      deletion syndrome. The 2.5 Mb region, located on 1p36.32-1pter, has a higher
      frequency of occurrence of tandem repeats and segmental duplications larger than
      1 kb, when compared with the 25.5 Mb of the complete 1p36 band. This could
      explain its proneness for involvement in chromosomal rearrangements in
      hematological neoplasias.

PMID- 15744522
TI  - Matrix Gla protein and osteopontin genetic associations with coronary artery
      calcification and bone density: the CARDIA study.
AB  - A role for matrix proteins has previously been proposed in the pathogenesis of
      arterial calcification in the setting of atherosclerosis, and a link has been
      suggested between osteoporosis and arterial calcification. Our aim has been to
      investigate whether matrix Gla protein (MGP) T-138C, osteopontin (SPP1) T-443C,
      and Asp94Asp single nucleotide polymorphisms are associated with the development
      of arterial calcification and bone density. The individual effects of the MGP and
      SPP1 polymorphisms with coronary calcification are weak and not statistically
      significant. Bone mineral density differences at both the hip and spine do not
      vary statistically by genotype for any of the polymorphisms studied. Given the
      significant role of both MGP and SPP1 in arteriosclerosis, further research in
      higher risk, older populations are needed to determine fully the way in which MGP
      and SPP1 polymorphisms are associated with disease.

PMID- 15744523
TI  - A neutral variant involved in a complex CFTR allele contributes to a severe
      cystic fibrosis phenotype.
AB  - In order to further elucidate the contribution of complex alleles to the wide
      phenotypic variability of cystic fibrosis (CF), we investigated the structure
      function relationships of a severe CF-associated complex allele
      [p.S912L;p.G1244V]. To evaluate the contribution of each mutation to the
      phenotype, cystic fibrosis transmembrane conductance regulator (CFTR) mutants
      were expressed in HeLa cells and analysed for protein processing and Cl- channel
      activity. Both p.G1244V and [p.S912L;p.G1244V] mutants had normal protein
      processing but markedly decreased Cl- channel activity compared with wild-type.
      Notably, the double mutant displayed a dramatic decrease in Cl- channel activity
      compared with p.G1244V (P<0.001). p.S912L had normal protein processing and no
      detectable impact on CFTR function. In other respects, the p.S912L variation was
      identified in compound heterozygosity with p.R709X in a healthy fertile man.
      Together, these data strongly support the view that p.S912L in isolation should
      be considered as a neutral variant but one that might significantly impair CFTR
      function when inherited in cis with another CFTR mutation. Our data also further
      document the contribution of complex alleles to the wide phenotypic variability
      of CF. The results of functional studies of such complex alleles in other genetic
      diseases are discussed.

PMID- 15744524
TI  - Thalidomide in combination with dexamethasone for pretreated patients with
      multiple myeloma: serum level of soluble interleukin-2 receptor as a predictive
      factor for response rate and for survival.
AB  - The aim of this study was to assess the side effects and the efficacy of
      thalidomide alone or in combination with dexamethasone in relapsed multiple
      myeloma (MM) and to evaluate possible predictive factors for response rate and
      survival. Twenty-nine pretreated patients were enrolled, including 13 patients
      with a relapse after high-dose chemotherapy. The median number of relapses was 3
      (range: 1-7). Twenty-two patients received thalidomide in combination with
      dexamethasone and seven patients thalidomide alone. The dosage of thalidomide was
      400 mg/day and the dosage of dexamethasone 20 mg/m2 daily for 4 consecutive days
      every 3 weeks. Cycles of dexamethasone were given until maximal decline of
      myeloma protein was achieved, whereas therapy with thalidomide was maintained
      until disease progression. Responses occurred in 62% of patients, including 5
      (17%) complete remissions and 13 (45%) partial remissions. The median event-free
      survival (EFS) was 7.2 months and the median overall survival (OS) 26.1 months.
      In multivariate analysis, pretreatment serum levels of soluble interleukin-2
      receptor (sIL-2R) were a significant prognostic factor for EFS, and those of
      beta2-microglobulin (beta2M) and sIL-2R for OS. Serum levels of sIL-2R
      significantly increased after 3 weeks of treatment in 89% of patients, possibly
      representing lymphocyte activation induced by thalidomide. Two patients died of
      septic complications within 3 months after starting treatment with thalidomide
      and dexamethasone and one patient of herpes encephalitis after 26 months of
      treatment with thalidomide alone. Also, one case of pneumonia and one case of
      deep venous thrombosis of the lower limb occurred. Other side effects were
      somnolence, peripheral neuropathy, and bradycardia occurring in 35, 55, 38 and
      55% of patients, respectively. The combination of thalidomide and dexamethasone
      is an effective therapy in heavily pretreated myeloma patients with a high
      response rate and acceptable toxicities. A powerful predictive factor both for
      EFS and OS was the pretreatment serum level of sIL-2R.

PMID- 15744525
TI  - Bilateral retinal venous occlusion in pigmentary glaucoma.
AB  - BACKGROUND: The association of central retinal vein occlusion with primary open
      angle glaucoma is well known. This communication reports the occurrence of branch
      retinal vein occlusion and central retinal vein occlusion in a case of pigmentary
      glaucoma. METHODS: A 32-year-old man presented with old branch retinal vein
      occlusion in one eye and resolving central retinal vein occlusion in the other
      eye. Examination revealed bilateral Krukenberg's spindle and hyperpigmented
      trabecular meshwork. Intraocular pressure was 30 mmHg OU. Topical antiglaucoma
      medication was prescribed. RESULTS: Intraocular pressure was controlled with
      topical antiglaucoma medication. CONCLUSION: The present report suggests that
      intraocular pressure monitoring is important in eyes even with branch retinal
      vein occlusion. Pigment dispersion may be the underlying cause for bilateral
      retinal vein occlusion, especially in young patients.

PMID- 15744526
TI  - Does intravitreal triamcinolone acetonide-assisted peeling of the internal
      limiting membrane effect the outcome of macular hole surgery?
AB  - PURPOSE: To evaluate functional and anatomical outcome of triamcinolone acetonide
      assisted internal limiting membrane (ILM) peeling in patients with macular hole.
      METHODS: Fifteen eyes of 15 consecutive patients were identified with stage 3 and
      4 idiopathic macular holes, these undergoing triamcinolone acetonide assisted ILM
      peeling for macular holes. These were matched retrospectively with 15 eyes of 15
      patients with stage 3 and 4 idiopathic macular holes of less than six months
      duration, who underwent macular hole surgery with ILM peel augmented with
      indocyanine green (ICG). Functional and anatomical outcomes were compared between
      two groups. RESULTS: There were no significant differences between the two groups
      with reference to demographic features of age, sex, staging of the macular holes
      and the proportion subsequently undergoing cataract surgery. The mean follow-up
      period was 6.4 months in the triamcinolone acetonide group and 7.2 months in the
      ICG group. The hole closure rate was 100% in both group at primary operation. The
      mean Snellen line change was +1.24 in the intravitreal triamcinolone group and
      +1.1 in the ICG group. There was a significant improvement in Snellen and Logmar
      visual acuity in both groups. These differences in visual outcome between the
      groups were not statistically significant. CONCLUSIONS: Our data showed similar
      outcomes for patients with macular hole where ICG has been used when compared to
      patients where triamcinolone acetonide has been used for ILM peeling. Further
      study with longer follow-up and large series is warranted to assess the safety of
      the triamcinolone acetonide assisted ILM peeling in macular hole surgery.

PMID- 15744528
TI  - In vivo confocal microstructural analysis of corneal endothelial changes in a
      patient on long-term chlorpromazine therapy.
AB  - BACKGROUND: Deposits in the cornea and lens are a known complication of long-term
      chlorpromazine therapy. METHOD: A 59-year-old woman had previously taken
      chlorpromazine for 20 years with doses up to 1,200 mg/day, with a mean dose of
      400 mg/day. She presented with gradual onset of blurred vision in her left eye.
      Slit-lamp biomicroscopy revealed multiple fine creamy-white deposits on her
      corneal endothelium and anterior crystalline lens capsule bilaterally. RESULTS:
      In vivo confocal microscopy of the cornea identified irregular hyper-reflective
      deposits on the posterior surface of the endothelium. The deposits varied from 1
      microm to 70 microm in diameter and had well-defined edges. Endothelial
      morphology was otherwise normal bilaterally. CONCLUSIONS: This is the first
      report of in vivo confocal imaging of deposits resulting from long-term
      chlorpromazine use. Microstructural analysis of the corneal endothelium reveals
      that there were no abnormalities in cellular morphology resulting from these
      deposits.

PMID- 15744527
TI  - Angiographic findings in arteriovenous dissection (sheathotomy) for decompression
      of branch retinal vein occlusion.
AB  - BACKGROUND: Arteriovenous dissection (sheathotomy) is a new therapeutic option in
      patients with branch retinal vein occlusion (BRVO) and macular involvement. We
      present an angiographic follow-up of 22 patients who underwent arteriovenous
      dissection (AVD). METHODS: Twenty-two patients (15 women; mean age 68.7+/-8.0
      years) were examined preoperatively and 6 weeks, 3 months, 6 months, and 1 year
      after AVD. For assessment of retinal hemodynamics, arteriovenous passage time
      (AVP) of the affected and unaffected branches at first (AVPe) and at maximal
      (AVPmax) venous filling were measured. Changes in the foveal avascular zone (FAZ)
      were calculated to determine foveal structural changes. Visual acuity was
      assessed as functional parameter. RESULTS: The early AVP (AVPe) of the affected
      branch increased from 4.4+/-0.8 s preoperatively to 4.9+/-0.6 s 6 weeks after
      surgery and decreased to 2.7+/-0.4 s 1 year after surgery (p=0.05). When compared
      to the unaffected control branch, AVPe was significantly increased in the
      affected branch preoperatively (4.5+/-0.8 s versus 1.5+/-0.2 s, p<0.01), 6 weeks
      (4.9+/-0.6 s versus 2.1+/-0.3 s, p<0.01), 3 months (2.7+/-0.4 s versus 1.5+/-0.2
      s, p<0.01), and 6 months (3.1+/-0.4 s versus 2.2+/-0.3 s, p=0.02) after AVD.
      After 1 year, AVPe no longer differed between the affected and the control branch
      (2.7+/-0.4 s versus 2.6+/- 0.3 s). AVPmax was significantly increased in the
      affected branch preoperatively (11.8+/-0.8 s versus 7.7+/-1.0 s, p<0.05). The
      AVPmax in the affected branch with the exception of 3 months after surgery
      (10.2+/-1.1 s, p<0.01) was no longer elevated when compared to preoperative
      values. The area of the FAZ did not change significantly but showed a trend for
      enlargement. CONCLUSION: AVD for decompression of BRVO leads to a significant
      decrease of AVP and may ameliorate retinal perfusion in the affected branch.

PMID- 15744529
TI  - A prospective, open-label, dose-escalating study of low molecular weight heparin
      during repeat vitrectomy for PVR and severe diabetic retinopathy.
AB  - BACKGROUND: To determine the maximum tolerated dose (MTD) of enoxaparin, a low
      molecular weight heparin (LMWH) was used during repeat vitrectomy for
      rhegmatogenous retinal detachment with proliferative vitreoretinopathy (PVR) and
      severe diabetic retinopathy. METHODS: From 25 patients, 29 eyes undergoing repeat
      vitrectomy for PVR (CP3 or greater) or severe diabetic retinopathy were included
      in the study. Patients had previously undergone an average of 2.1 previous
      vitrectomies (range 1-5). Enoxaparin was added to the infusion fluid in an
      escalating dose from 0.1 IU/ml to 6.0 IU/ml as tolerated. Intraoperative
      bleeding, postoperative fibrin, hyphema and vitreous hemorrhage were graded in an
      unmasked fashion using previously described grading scales. RESULTS: All patients
      completed the study, and the study was able to achieve the 6.0 IU/ml maximum dose
      on the dose escalation schedule. No patient experienced dose-limiting toxicity.
      Analysis showed no increase in intraoperative bleeding complications between low
      dose (<or=1.0 IU/ml) and high dose (>1.0 IU/ml) enoxaparin (Mann-Whitney Test,
      P=0.029). CONCLUSIONS: Enoxaparin dose escalation did not result in a dose
      dependent increase in acute side effects. The establishment of a well-tolerated
      dose of enoxaparin during repeat vitrectomy for PVR and severe diabetic
      retinopathy (6.0 IU/ml) provides a foundation for future studies.

PMID- 15744530
TI  - Prevalence and progression of impaired glucose homeostasis assessed by the
      different criteria for IFG in Japanese adults.

PMID- 15744531
TI  - A novel functional polymorphism (-336A/G) in the promoter of the partitioning
      defective protein-6alpha gene is associated with increased glucose tolerance and
      lower concentrations of serum non-esterified fatty acids.
AB  - AIMS/HYPOTHESIS: Partitioning-defective protein-6alpha (Par6alpha) has recently
      been demonstrated to negatively regulate insulin signalling in murine myoblasts.
      To address whether Par6alpha plays a role in human physiology, the present study
      investigated whether mutations exist in the Par6alpha gene and whether these
      mutations, if present, are associated with pre-diabetic phenotypes in non
      diabetic subjects. METHODS: The complete gene (part of the promoter [2.1 kb], all
      exons/introns and the 3' untranslated region) encoding Par6alpha was analysed in
      664 non-diabetic subjects. We investigated possible associations between single
      nucleotide polymorphisms and percentage of body fat, glucose tolerance (as
      determined by OGTT), serum NEFA concentrations and whole-body insulin sensitivity
      (estimated during the OGTT, and for a subgroup of 242 subjects determined by the
      euglycaemic-hyperinsulinaemic clamp). RESULTS: A rare A/G polymorphism was found
      336-bp upstream of the translational start codon (allele frequency 0.03). The
      data for subjects homozygous and heterozygous for -336G (R/G, n=43) were combined
      and compared with those for subjects homozygous for -336A (A/A, n=621). Subjects
      with the R/G genotype had lower fasting (4.84+/-0.09 mmol/l, means+/-SEM,
      p=0.049) and 2-h (5.50+/-0.02 mmol/l, p=0.050) plasma glucose concentrations than
      subjects with the A/A genotype (5.02+/-0.02 and 5.94+/-0.06 mmol/l,
      respectively). Subjects with the R/G genotype also had lower fasting (448+/-31
      micromol/l, p=0.018) and 2-h serum NEFA concentrations (61+/-7 micromol/l,
      p=0.015) than subjects with the A/A genotype (529+/-9 and 75+/-2 micromol/l,
      respectively), adjusted for age, sex and percentage of body fat. There were no
      differences in adiposity or whole-body insulin sensitivity between the two
      genotype groups (all p>0.36). A luciferase reporter gene assay revealed that the 
      336G promoter variant had a significantly lower (-22.8%, p=0.006) transcriptional
      activity in transfected C2C12 murine myoblasts than the -336A promoter variant.
      CONCLUSIONS/INTERPRETATION: A novel functional variant in the promoter of the
      Par6alpha gene is associated with reduced fasting glycaemia, increased glucose
      tolerance and reduced serum NEFA concentrations.

PMID- 15744532
TI  - Comparative evaluation of simple insulin sensitivity methods based on the oral
      glucose tolerance test.
AB  - AIMS/HYPOTHESIS: We compared five surrogate insulin sensitivity (IS) methods
      against the euglycaemic-hyperinsulinaemic clamp. These methods were the
      homeostasis model assessment (HOMA) and four methods based on the OGTT (OGIS,
      MCRest, ISIcomp, SIORAL). METHODS: We compared these IS methods against the clamp
      (0.28 nmol.min(-1).m(-2) insulin infusion) M value in 147 women (58-61 years; BMI
      19-38 kg/m2; 116 NGT, 25 IFG/IGT, six type 2 diabetic), by evaluating the
      correlation coefficient with M. We also tested the ability to reproduce the
      relationships between IS and typical IS correlates (BMI, fasting insulin, insulin
      to glucose OGTT area ratio and fasting, 2 h and mean glucose) by means of the
      "discrepancy index" D, in which (1) D=0 if the correlation between IS and the
      variable of interest is as with the clamp, (2) D is smaller than 0 if the
      correlation is overestimated, and (3) D is greater than 0 if underestimated.
      RESULTS: All IS methods correlated with M (r=0.57-0.83, p<0.0001); for MCRest the
      relationship was markedly curvilinear. All IS measures correlated with the
      considered variables (r=0.29-0.94, p<0.0005); however, no method had D
      approximately 0 for all variables. The best surrogates of M were OGIS (one D not
      =0) and MCRest (two D not =0); the other methods either under- or overestimated
      the degree of correlation (three or more D not =0), in particular with fasting
      insulin (HOMA: D=-57%; ISIcomp: D=-36%) and BMI (HOMA: D=-14%; ISIcomp: D=-14%;
      SiORAL: D=-11%). CONCLUSIONS/INTERPRETATION: All IS methods were correlated with
      M. OGIS and MCRest were preferable to the other methods and in particular to HOMA
      for reproducing relationships with the independent variables.

PMID- 15744533
TI  - Fat distribution is strongly associated with plasma glucose levels and diabetes
      in Thai adults-the InterASIA study.
AB  - AIMS/HYPOTHESIS: Asian populations have high risks of disease at low levels of
      BMI and weight, possibly because of high rates of abdominal obesity. In such
      populations, waist circumference and WHR (measures of fat distribution) may
      better capture the effects of adiposity. METHODS: The strengths of the
      associations between different measures of adiposity and glucose levels and
      diabetes were investigated in the Thai component of the International
      Collaborative Study of Cardiovascular Disease in Asia (InterASIA), a multi-stage
      cross-sectional survey of risk factors in Thai adults aged 35 years or over. The
      analyses included 5,302 men and women. RESULTS: All four measures of adiposity
      were positively associated with plasma glucose and the odds of having diabetes
      (all p<0.001), but the associations were stronger for measures of fat
      distribution. The age- and sex-adjusted fasting plasma glucose level increased
      linearly across each fifth of weight, BMI, waist and WHR by 0.12 mmol/l (SE
      0.02), 0.12 (0.02), 0.17 (0.02) and 0.16 (0.02), respectively. The corresponding
      odds ratios for diabetes were 1.41 (95% CI 1.27-1.56), 1.43 (1.28-1.59), 1.64
      (1.47-1.83) and 1.70 (1.52-1.90), respectively. Multivariate analyses
      incorporating different combinations of adiposity measures, as well as analyses
      of receiver operating characteristics, confirmed the greater predictive value of
      measures of fat distribution. CONCLUSIONS/INTERPRETATION: Waist circumference and
      WHR were more strongly associated with fasting plasma glucose and diabetes than
      were weight and BMI. These measures of abdominal adiposity are likely to be more
      useful for assessing the obesity-related risk of cardiovascular diseases in Asian
      populations.

PMID- 15744535
TI  - The role of the proteasome in generating cytotoxic T-cell epitopes: insights
      obtained from improved predictions of proteasomal cleavage.
AB  - Cytotoxic T cells (CTLs) perceive the world through small peptides that are eight
      to ten amino acids long. These peptides (epitopes) are initially generated by the
      proteasome, a multi-subunit protease that is responsible for the majority of
      intra-cellular protein degradation. The proteasome generates the exact C-terminal
      of CTL epitopes, and the N-terminal with a possible extension. CTL responses may
      diminish if the epitopes are destroyed by the proteasomes. Therefore, the
      prediction of the proteasome cleavage sites is important to identify potential
      immunogenic regions in the proteomes of pathogenic microorganisms (or humans). We
      have recently shown that NetChop, a neural network-based prediction method, is
      the best method available at the moment to do such predictions; however, its
      performance is still lower than desired. Here, we use novel sequence encoding
      methods and show that the new version of NetChop predicts approximately 10% more
      of the cleavage sites correctly while lowering the number of false positives with
      close to 15%. With this more reliable prediction tool, we study two important
      questions concerning the function of the proteasome. First, we estimate the N
      terminal extension of epitopes after proteasomal cleavage and find that the
      average extension is relatively short. However, more than 30% of the peptides
      have N-terminal extensions of three amino acids or more, and thus, N-terminal
      trimming might play an important role in the presentation of a substantial
      fraction of the epitopes. Second, we show that good TAP ligands have an increased
      chance of being cleaved by the proteasome, i.e., the specificity of TAP has
      evolved to fit the specificity of the proteasome. This evolutionary relationship
      allows for a more efficient antigen presentation.

PMID- 15744536
TI  - Association between asthma-related phenotypes and the CC16 A38G polymorphism in
      an unselected population of young adult Danes.
AB  - The gene for Clara cell 16-kDa (CC16) protein is a promising candidate for asthma
      susceptibility. The CC16 38A allele has been associated with decreased CC16
      plasma levels and increased incidence of asthma in Australian children. To date
      these results have not been replicated in adults. Therefore, potential links
      between CC16 A38G, asthma and atopy were investigated in an unselected population
      of young adult Danes. Four hundred sixty-four Danes, aged 19-29 years, from
      Copenhagen participated in an asthma and allergy phenotype-genotype study.
      Genotyping was done by Sau96I restriction digestion of PCR products spanning the
      A38G polymorphism. Potential A38G genotype and asthma-related phenotype
      associations were investigated using regression analysis, adjusting for potential
      confounders where appropriate. Adults with the 38AA genotype had higher odds of
      current asthma (OR 3.2, P=0.013) and ever asthma (OR 2.2, P=0.045) compared with
      those with the 38GG genotype. Adjusting for atopy had minimal effect on this
      relationship. A positive linear trend was evident between the 38A allele and
      atopic dermatitis (OR 1.67, P=0.02). No associations were found between the A38G
      polymorphism and rhinitis, atopy, forced expiratory volume in 1 s (FEV(1)),
      forced vital capacity (FVC), airway responsiveness (AR) to histamine or
      peripheral blood eosinophil level (PBEL). An atopy-independent association
      between CC16 38AA and asthma prevalence was identified, suggesting the CC16 38A
      allele predisposes to adult asthma independent of Th1/Th2 processes. This finding
      is consistent with previous studies in children, but is the first reported
      association between CC16 A38G and asthma in adults. CC16 38A also displayed a
      positive linear trend with atopic dermatitis.

PMID- 15744537
TI  - The synthetic form of a novel chicken beta-defensin identified in silico is
      predominantly active against intestinal pathogens.
AB  - Antimicrobial peptides are essential components of innate immunity and are
      generally thought to act by disrupting the membrane integrity of microbes. Here
      we report the discovery of two novel chicken beta-defensins, gallinacin (Gal)-11
      and Gal-12, found by hidden Markov model profile searching of the chicken genome.
      We have sequenced the genes and elucidated the 3'UTR of Gal-11. Differential mRNA
      expression of these novel genes has been shown across a panel of chicken tissues.
      Gal-11 mRNA was highly expressed in the small intestine, the liver, the gall
      bladder and the spleen and also showed moderate expression in several other areas
      of the chicken anatomy, whilst Gal-12 mRNA was found only in the liver and the
      gall bladder. Antimicrobial activity of synthetic Gal-11 has been demonstrated
      against a range of bacteria and is predominantly active against the intestinal
      pathogens Salmonella typhimurium and Listeria monocytogenes.

PMID- 15744538
TI  - Characterisation of a cluster of TRIM-B30.2 genes in the chicken MHC B locus.
AB  - We have identified and characterised a cluster of six TRIM-B30.2 genes flanking
      the chicken BF/BL region of the B complex. The TRIM-B30.2 proteins are a subgroup
      of the TRIM protein family containing the tripartite motif (TRIM), consisting of
      a RING domain, a B-box and a coiled coil region, and a B30.2-like domain. In
      humans, a cluster of seven TRIM-B30.2 genes has been characterised within the MHC
      on Chromosome 6p21.33. Among the six chicken TRIM-B30.2 genes two are orthologous
      to those of the human MHC, and two (TRIM41 and TRIM7) are orthologous to human
      genes located on Chromosome 5. In humans, these last two genes are adjacent to
      GNB2L1, a guanine nucleotide-binding protein gene, the ortholog of the chicken
      c12.3 gene situated in the vicinity of the TRIM-B30.2 genes. This suggests that
      breakpoints specific to mammals have occurred and led to the remodelling of their
      MHC structure. In terms of structure, like their mammalian counterparts, each
      chicken gene consists of five coding exons; exon 1 encodes the RING domain and
      the B-box, exons 2, 3 and 4 form the coiled-coil region, and the last exon
      represents the B30.2-like domain. Phylogenetic analysis led us to assume that
      this extended BF/BL region may be similar to the human extended class I region,
      because it contains a cluster of BG genes sharing an Ig-V like domain with the
      BTN genes (Henry et al. 1997a) and six TRIM-B30.2 genes containing the B30.2-like
      domain, shared with the TRIM-B30.2 members and the BTN genes.

PMID- 15744540
TI  - Survival, complications and outcome in 282 patients operated for neurological
      deficit due to thoracic or lumbar spinal metastases.
AB  - We present survival, neurological function, and complications in a consecutive
      series of 282 patients operated for spinal metastases from January 1990 to
      December 2001. Our main surgical indication throughout this time period was
      neurological deficit rather than pain. Metastases from cancer of the prostate
      accounted for 40%, breast 15%, kidney 8%, and lung 7%. In 78% the level of
      decompression was thoracic and lumbar in 22%. Thirteen percent had a single
      metastases only, 64% had multiple skeletal metastases, and 23% had non-skeletal
      metastases also. Preoperatively 64% were non-walkers (Frankel A-C), 30% could
      walk with aids (Frankel D) and 8% had normal motor function (Frankel E).
      Posterior decompression and stabilization was applied in 212 patients, 47 had
      laminectomy only, and 23 had anterior decompressions and reconstruction.
      Complications were recorded at a level of 20%, and systemic complications were
      often associated with early death. The survival rate was 0.63 at 3 months, 0.47
      at 6 months, 0.30 at 1 year, and 0.16 at 2 years. Twelve of 255 (5%) patients
      with motor deficits were worsened postoperatively, whereas 179 (70%) improved at
      least one Frankel grade. The ability to walk postoperatively was retained during
      follow-up in more than 80% of the patients. This study shows that important
      improvement of function can be gained by surgical treatment, but the complication
      rate was high and many patients died of their disease within the first months of
      surgery.

PMID- 15744541
TI  - Percutaneous radiofrequency coagulation of osteoid osteoma of the "Neural Spinal
      Ring".
AB  - STUDY DESIGN: Three cases of osteoid osteomas of the spine, adjacent to neural
      elements, were treated with CT-guided thermal coagulation. OBJECTIVE: To present
      an alternative method to conventional treatment of spinal osteoid osteoma.
      SUMMARY OF BACKGROUND DATA: Percutaneous CT-guided radiofrequency coagulation has
      been successfully used for osteoid osteoma of the extremities. The conventional
      management of spinal osteoid osteoma is by surgical resection. METHOD: Three
      patients with osteoid osteoma of the spine, adjacent to neural structures, were
      treated by percutaneous radiofrequency ablation. The procedure was performed in
      the CT room under general anesthesia and CT guidance. The thermocoagulation
      electrode was heated at 90 degrees C for 4 min. RESULTS: Two patients left the
      hospital the same day; the third one was kept 24 h for observation. All of them
      had total pain relief within 48 h following the procedure. No complications were
      recorded. There was no evidence of recurrence after a mean follow-up period of 17
      months. CONCLUSION: Osteoid osteoma of the spine, adjacent to neural structures,
      can effectively and safely be treated by minimally invasive percutaneous CT
      guided radiofrequency coagulation.

PMID- 15744539
TI  - Agrobacterium T-DNA integration in Arabidopsis is correlated with DNA sequence
      compositions that occur frequently in gene promoter regions.
AB  - Mobile insertion elements such as transposons and T-DNA generate useful genetic
      variation and are important tools for functional genomics studies in plants and
      animals. The spectrum of mutations obtained in different systems can be highly
      influenced by target site preferences inherent in the mechanism of DNA
      integration. We investigated the target site preferences of Agrobacterium T-DNA
      insertions in the chromosomes of the model plant Arabidopsis thaliana. The
      relative frequencies of insertions in genic and intergenic regions of the genome
      were calculated and DNA composition features associated with the insertion site
      flanking sequences were identified. Insertion frequencies across the genome
      indicate that T-strand integration is suppressed near centromeres and rDNA loci,
      progressively increases towards telomeres, and is highly correlated with gene
      density. At the gene level, T-DNA integration events show a statistically
      significant preference for insertion in the 5' and 3' flanking regions of protein
      coding sequences as well as the promoter region of RNA polymerase I transcribed
      rRNA gene repeats. The increased insertion frequencies in 5' upstream regions
      compared to coding sequences are positively correlated with gene expression
      activity and DNA sequence composition. Analysis of the relationship between DNA
      sequence composition and gene activity further demonstrates that DNA sequences
      with high CG-skew ratios are consistently correlated with T-DNA insertion site
      preference and high gene expression. The results demonstrate genomic and gene
      specific preferences for T-strand integration and suggest that DNA sequences with
      a pronounced transition in CG- and AT-skew ratios are preferred targets for T-DNA
      integration.

PMID- 15744542
TI  - The vertebral interbody grafting site's low concentration in osteogenic
      progenitors can greatly benefit from addition of iliac crest bone marrow.
AB  - The ability of bone substitutes to promote bone fusion is contingent upon the
      presence of osteoinductive factors in the bone environment at the fusion site.
      Osteoblast progenitor cells are among these environmental osteoinductive factors,
      and one of the most abundant and available sources of osteoblastic cells is the
      bone marrow. As far as biological conditions are concerned, the vertebral
      interbody space appears as a favorable site for fusion, as it is surrounded by
      spongy bone, theoretically rich in osteogenic cells. This site may, however, not
      be as rich in osteogenic precursor cells especially at the time of grafting,
      because decortication of the vertebral end plates during the grafting process may
      modify cell content of the surrounding spongy bone. We tested this hypothesis by
      comparing the abundance of human osteogenic precursor cells in bone marrow
      derived from the iliac crest, the vertebral body, and the decorticated
      intervertebral body space. The number of potential osteoblast progenitors in each
      site was estimated by counting the alkaline phosphatase-expressing colony-forming
      units (CFU-AP). The results, however, demonstrate that the vertebral interbody
      space is actually poorer in osteoprogenitor cells than the iliac crest (P<0.001)
      and vertebral body (P<0.01), especially at the time of graft implantation. In
      light of our results, we advocate addition of iliac crest bone marrow aspirate to
      increase the success rate of vertebral interbody fusion.

PMID- 15744544
TI  - Commotio cordis--a report of three cases.
AB  - Commotio cordis is a recognised cause of sudden death in which an apparently
      minor blow to the chest causes ventricular fibrillation and cardiac arrest. It is
      best known for causing death during games of youth baseball in the United States,
      but individual cases have been recorded as a result of a wide range of
      activities, principally sporting. The underlying biochemical and mechano-electric
      causes have been well documented. However, there are few reported cases where
      commotio cordis is implicated as the cause of death in homicide cases. We present
      three cases from the north-east of England where an assault caused death by this
      mechanism.

PMID- 15744543
TI  - NMDA or AMPA/kainate receptor blockade prevents acquisition of conditioned place
      preference induced by D(2/3) dopamine receptor stimulation in rats.
AB  - RATIONALE: Recent experiments from this laboratory demonstrated synergistic
      effects of AMPA/kainate receptor blockade and D(2/3) dopamine (DA) receptor
      stimulation on brain stimulation reward and locomotor activity. OBJECTIVES: Using
      place conditioning, this study explored further the interaction between DA and
      glutamate (Glu) using the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801,
      the AMPA/kainate receptor antagonist NBQX, and the D(2/3) DA receptor agonist 7
      OH-DPAT. METHODS: Effects of these compounds, alone and combined, were measured
      in male Sprague--Dawley rats using an unbiased two-compartment place conditioning
      procedure. RESULTS: 7-OH-DPAT (0.03--5.0 mg kg(-1), s.c.) administered
      immediately prior to conditioning was ineffective; when administered 15 min prior
      to conditioning, only the highest dose (5.0 mg kg(-1), s.c.) induced conditioned
      place preference (CPP). Acquisition of 7-OH-DPAT-induced CPP was blocked by MK
      801 (0.06 or 0.13 mg kg(-1), i.p.) or NBQX (0.5 microg) microinjected into the
      nucleus accumbens (NAS) shell subregion. Intra-NAS shell administration of 7-OH
      DPAT (5.0 microg) or NBQX (0.5 microg), alone or combined, failed to induce place
      conditioning, and this lack of effect was not due to state dependency.
      Administration of MK-801 or 7-OH-DPAT (5.0 mg kg(-1)) during the conditioning
      phase acutely increased horizontal activity, but neither compound, alone or
      combined, induced conditioned locomotor effects. CONCLUSIONS: Acquisition of
      place conditioning induced by systemic administration of 7-OH-DPAT is blocked by
      systemic NMDA receptor antagonism by MK-801 or by the AMPA/kainate receptor
      antagonist NBQX microinjected into the NAS shell subregion.

PMID- 15744545
TI  - Heat stroke in an incubator: an immunohistochemical study in a fatal case.
AB  - The authors report the unique case of an 8-day-old infant succumbing to heat
      stroke caused by an abnormal increase of the environmental temperature in an
      incubator. At postmortem examination, second-degree burns were detected, and
      macroscopic and microscopic findings were typical for a heat-related death. An
      immunohistochemical study was performed. At the same time, a detailed examination
      of the incubator was conducted, revealing a malfunctioning of the temperature and
      relative humidity control system. We suggest that the diagnosis of heat stroke
      has to be confirmed on the basis of a detailed postmortem examination and a
      complete immunohistochemical investigation of heat shock proteins, molecules
      produced acutely in response to heat stress.

PMID- 15744546
TI  - HELLP syndrome as a cause of unexpected rapid maternal death--a case report and
      review of the literature.
AB  - Unexpected rapid death after delivery due to HELLP syndrome (HS) may become the
      subject of a forensic expertise. Since this syndrome is rarely encountered in
      forensic pathology, our objective was to point to some specific findings which
      might present forensic aspects of HS. These include unexpectedness, suddenness
      and fulminant course of this syndrome, which may confuse physicians, and on the
      other hand these characteristics cast doubt on violent injury, diagnostic
      oversights or iatrogenic injuries. Absence of classical signs of preeclampsia and
      non-specific clinical symptoms cause considerable differential diagnostic
      problems leading to a diagnostic delay or initial wrong non-obstetric diagnosis.
      A definitive postmortem diagnosis of HS in questionable cases of maternal death
      and consecutive forensic expertise of suspected medical malpractice should be
      based on accepted laboratory criteria and characteristic histopathological
      alterations.

PMID- 15744547
TI  - Drotrecogin alfa (activated, Xigris) in combination with heparin or melagatran:
      an in vitro investigation.
AB  - BACKGROUND: The present in vitro study of human plasma investigated the
      anticoagulant effects of recombinant human activated protein C (rhAPC;
      drotrecogin alfa [activated, Xigris]), combined with either unfractionated
      heparin (UH) or the direct thrombin inhibitor melagatran. METHODS: Prolongation
      of clotting time and generation of prothrombin fragments 1 and 2 (F1 + 2) and of
      thrombin-antithrombin (TAT) complex were measured in vitro. Clot formation was
      induced by adding low levels (final concentration, 20 pmol/L) of lipidated tissue
      factor (TF) to citrated venous plasma samples from healthy human volunteers (n =
      16). It has been suggested that experimental activation of plasma with low levels
      of TF more closely simulates conditions in vivo. RESULTS: rhAPC, melagatran, or
      UH alone concentration-dependently prolonged the clotting time and suppressed F1
      + 2 and TAT generation. rhAPC-mediated prolongation of clotting time
      concentration-dependently increased with the addition of either UH or melagatran,
      the effect being more pronounced with the addition of melagatran. Similarly,
      rhAPC-mediated generation of F1 + 2 and TAT also increased concentration
      dependently with the addition of either UH or melagatran; the effect being, in
      this case, more pronounced with the addition of UH. CONCLUSIONS: This study
      demonstrated the effects of rhAPC, alone and combined with either UH or
      melagatran, on clotting time and markers of thrombin generation in human plasma.
      These results may guide facilitate estimation of appropriate doses of rhAPC and
      melagatran in future clinical trials.

PMID- 15744548
TI  - GPIIb/IIIa inhibitor-induced dethrombosis.
AB  - GPIIb/IIIa inhibitors have demonstrated clinical benefit in patients with acute
      coronary syndromes and in those undergoing percutaneous coronary intervention. As
      opposed to the well documented prevention of platelet aggregation by GPIIb/IIIa
      inhibitors, we here discuss the less well appreciated reversal of platelet
      aggregation by, and dethrombotic effects of, GPIIb/IIIa inhibitors. In vivo
      evidence for GPIIb/IIIa inhibitor-induced dethrombosis includes animal models of
      arterial thrombosis and human studies (both observational and randomized clinical
      trials) in the setting of acute myocardial infarction. These human studies
      demonstrated increased coronary perfusion prior to percutaneous coronary
      intervention in patients receiving GPIIb/IIIa inhibitors as compared to those
      patients receiving placebo. Mechanisms of GPIIb/IIIa inhibitor-induced
      dethrombosis include alterations in thrombus size and structure, reduced capacity
      for subsequent thrombus growth, inhibition of soluble CD40L release from
      platelets, and a direct platelet disaggregatory effect that parallels
      fibrinogen's interactions with GPIIb/IIIa. In summary, mechanistic studies,
      animal models, human observational studies and randomized clinical trials all
      strongly suggest that GPIIb/IIIa inhibitors have a direct dethrombotic effect in
      addition to their well-described preventative effects on platelet aggregation.

PMID- 15744549
TI  - The effect of temperature variation in vitro on platelet-leukocyte interactions
      and individual prothrombotic potential.
AB  - BACKGROUND: Temperature variation within human atheromatous plaques, a finding
      which supports inflammatory cell-mediated thermogenesis, predicts clinical events
      among patients with coronary artery disease. PURPOSE: Our study was designed to
      investigate the effect of ambient temperature in vitro on platelet-leukocyte
      interactions, monocyte tissue factor expression and platelet-dependent thrombin
      generation. METHODS/RESULTS: Whole blood samples obtained from healthy volunteers
      were incubated at 37 degrees, 38 degrees and 39 degrees C for three hours.
      Platelet-leukocyte aggregates, determined by flow cytometry before and after
      stimulation with lipopolysaccharide (10 ng/ml), increased from 15.0 +/- 2.3% at
      37 degrees C to 19.4% at 38 degrees C (22.6% increase; p < 0.01), decreasing to
      12.2 +/- 0.9% at 39 degrees C. The responses for individual subpopulations of
      platelet-lymphocyte, platelet-neutrophil and platelet-monocyte heterotypic
      aggregates were similar. Monocyte tissue factor expression, quantitated by flow
      cytometry with CD14 and FITC-labeled anti-human tissue factor antibody stains,
      increased from 45.2 +/- 3.8% (37 degrees C) to 62.0 +/- 4.3 (38 degrees C),
      representing a 27.1% rise (p < 0.005). Changes in temperature did not influence
      the initiation or propagation phases of platelet-dependent thrombin generation.
      CONCLUSION: A modest increase in ambient temperature increases platelet-leukocyte
      and monocyte tissue factor expression, providing an additional mechanistic link
      between atherosclerosis, inflammation and thrombosis. Whether therapies designed
      to lower vessel wall temperature will provide an antithrombotic effect requires
      further evaluation.

PMID- 15744550
TI  - Does clopidogrel increase the degree of platelet inhibition when a platelet
      glycoprotein IIb/IIIa inhibitor has been given? Insights from an optical platelet
      aggregometry study.
AB  - INTRODUCTION: While the CURE trial demonstrated the benefits of clopidogrel in
      acute coronary syndromes, patients receiving glycoprotein IIb/IIIa antagonists
      were excluded. Given the frequent coadministration of these two medications, we
      sought to examine their interaction and their combined effect on platelet
      inhibition. METHODS: Ten patients admitted to the hospital with stable or
      unstable angina underwent phlebotomy prior to, three hours and six hours after
      administration of a standard oral loading dose of clopidogrel. The samples were
      then treated in vitro with incremental concentrations of tirofiban (0, 10, 20,
      40, 60, and 80 ng/mL), and optical platelet aggregometry was performed utilizing
      ADP and TRAP as agonists. We analyzed the combined effects of these agents using
      a mixed effects model with time and tirofiban concentration as fixed effects, and
      subject and timing of phlebotomy as random effects. RESULTS: There was no
      evidence of additional inhibition of platelet aggregation due to clopidogrel
      regardless of the concentration of tirofiban or the study agonist (ADP 20 muM or
      iso-TRAP). Specifically, there was no difference in the tirofiban dose-response
      curves with either platelet agonist for any of the three time points (before, and
      three and six hours after, clopidogrel administration). DISCUSSION: There is no
      evidence that the combination of clopidogrel and tirofiban achieves greater
      inhibition of platelet aggregation than tirofiban alone.

PMID- 15744551
TI  - Argatroban anticoagulation in conjunction with glycoprotein IIb/IIIa inhibition
      in patients undergoing percutaneous coronary intervention: an open-label,
      nonrandomized pilot study.
AB  - BACKGROUND: Argatroban, a direct thrombin inhibitor, blocks clot-bound thrombin
      more effectively than does heparin. This multicenter, prospective pilot study
      evaluated the efficacy and safety of argatroban in combination with glycoprotein
      IIb/IIIa inhibition in patients undergoing percutaneous coronary intervention.
      METHODS: Patients (N = 152) received argatroban as a 250- or 300-mug/kg bolus,
      followed by a 15-mug/kg/min infusion during percutaneous coronary intervention.
      An additional 150-mug/kg bolus was administered if activated clotting times 5-15
      min after initiating argatroban were <275 s. Abciximab (N = 150) or double-bolus
      eptifibatide (N = 2) was administered simultaneously. RESULTS: Median activated
      clotting times at the beginning and end of the procedure were approximately 300
      s. The primary efficacy endpoint-a composite of death, myocardial infarction, or
      urgent revascularization at 30 days-occurred in 4 (2.6%) patients (no death, 4
      myocardial infarctions, and 2 revascularizations). Two (1.3%) patients had major
      bleeding by the Thrombolysis in Myocardial Infarction criteria (1
      retroperitoneal, 1 groin hematoma). CONCLUSIONS: Argatroban in combination with
      glycoprotein IIb/IIIa inhibition appears to provide adequate anticoagulation and
      be well tolerated with an acceptable bleeding risk for patients undergoing
      percutaneous coronary intervention. Additional studies are warranted.

PMID- 15744552
TI  - Statin reduces the platelet P-selectin expression in atherosclerotic ischemic
      stroke.
AB  - Recently, it has been demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG Co-A) reductase inhibitor or statin can regulate the thrombogenesis beyond
      its lipid lowering effect. In this study, we investigated the beneficial effect
      of statin to reduce the platelet P-selectin expression in atherosclerotic
      ischemic stroke. Thirty-two (28 men, 4 women; mean age 59.8 +/- 9.6 years)
      patients with atherosclerotic ischemic stroke were assigned to receive
      simvastatin 20 mg per day for 12 weeks and discontinued for another 12 weeks.
      Then, administration of simvastatin was discontinued for the following 12 weeks.
      Using whole blood flow cytometry, we evaluated the change of platelet P-selectin
      expression of all the patients after the 12-weeks use and the 12-weeks
      discontinuance of simvastatin. The platelet P-selectin expression was significant
      reduced after treatment of simvastatin 20 mg for 12 weeks (p < 0.001). However,
      the effect of statin to reduce platelet P-selectin expression disappeared after
      12 weeks of cessation of statin. In addition, the P-selectin changes induced by
      statin were independent of the changes of the LDL cholesterol (r = -0.311, p =
      0.386). This study demonstrated that the use of statin might be a helpful add-on
      therapy to regulate the platelet related thrombogenesis in atherosclerotic
      ischemic stroke.

PMID- 15744554
TI  - Tenecteplase for the treatment of massive and submassive pulmonary embolism.
AB  - BACKGROUND: Data on thrombolytic therapy disclose benefits from thrombolytic
      therapy in patients with massive and submassive pulmonary embolism (PE).
      Previously published case reports have described the successful use of
      tenecteplase under these conditions. METHODS: Four patients with massive and
      submassive PE received a weight-optimized dosing regimen of tenecteplase,
      administered as an intravenous bolus. RESULTS: All patients experienced
      clinically relevant improvement of dyspnea following thrombus regression.
      Regression of right ventricular enlargement was documented in three cases.
      Tenecteplase was well tolerated and did not cause bleeding complications. Thirty
      day mortality was zero. CONCLUSIONS: These data support the use of this new
      thrombolytic agent in patients with massive and submassive PE; however,
      sufficiently powered, randomized trials have not yet taken place for these
      indications.

PMID- 15744553
TI  - Fibrinolysis of acute peripheral arterial occlusion with tenecteplase--a new
      weight-optimized treatment regimen.
AB  - Peripheral arterial occlusions are associated with high morbidity. Thrombolysis
      has become established as effective treatment in clinical practice. Tenecteplase
      is a new thrombolytic agent that offers advantages over existing drugs with
      respect to mechanism of action and adverse effects. This case report describes
      successful thrombolysis of an acute thromboembolic brachial artery subtotal
      occlusion in a 76-year-old woman. In contrast to previously published data,
      tenecteplase was administered in a weight-adapted dose regimen over six hours,
      with application of one-fourth of the dose usually given in patients with
      myocardial infarction. Tenecteplase was immediately effective, and proved safe
      and well tolerated.

PMID- 15744555
TI  - Some considerations about the composition, in vivo detection and therapeutic
      approaches to the coronary atherosclerotic plaques in diabetes mellitus.

PMID- 15744556
TI  - Optimizing heparin compounds: a working construct for future antithrombotic drug
      development.

PMID- 15744557
TI  - CD14-dependent modulation of transcriptional activities of endogenous
      retroviruses in the lung after injury.
AB  - Lipopolysaccharide (LPS) plays a central role in the pathogenesis of distant
      organs after burn. Recent studies demonstrated the regulation of mouse endogenous
      retroviruses (MuERVs) in several organs after burn. In this study, the role of
      CD14, a LPS receptor, in burn-mediated regulation of MuERV expression in the lung
      was investigated. CD14 knockout (KO) and wild type (WT) mice were subjected to
      burn followed by RT-PCR analysis of alterations in the MuERV expression in the
      lung 1 day after injury. Even without injury, CD14 KO mice had a unique profile
      of MuERV expression compared to WT. Three bands (Lung-1, Lung-2, and Lung-3) in
      CD14 KO were downregulated after injury. Lung-2 and Lung-3 transcripts were
      almost identical to 2 previously described defective env transcripts of MuERVs,
      respectively. The Lung-1-1 transcript was a double spliced message generated by
      the env and a set of novel splicing signals, whereas the Lung-1-2 transcript was
      a defective env transcript. Only the Lung-1-1 transcript had a significant ORF
      capable of encoding a gag-pol fusion polypeptide. Putative proviral sequences of
      Lung-1-1 and Lung-1-2 transcripts were mapped to chromosomes 4 and 11,
      respectively. The results from this study suggest that the absence of CD14
      expression in CD14 KO mice contributes to the transcriptional regulation of
      MuERVs in the lung after injury.

PMID- 15744558
TI  - Complete genome sequence and biological characterizations of a novel goose
      paramyxovirus-SF02 isolated in China.
AB  - A paramyxovirus designated as APMV-1 (NDV) isolate SF02 (abbre. as SF02) was
      recently isolated from goose in China. SF02 was identified as a member of
      Newcastle disease virus (NDV) genotype VII. NDV strains are generally pathogenic
      only for fowls, including chicken and pigeon, and not for waterfowls such as
      goose and duck, whereas SF02 is highly pathogenic for both fowls and waterfowls.
      In the present study the complete genome consisting of 15, 192 nucleotides of
      SF02 was sequenced. Genomes of SF02 and all known APMV-1, Strains contain 6 ORFs
      in the order of NP-P-M-F-HN-L, and that of SF02 had an extra 6 nts between NP and
      P genes. Moreover, an anti-sense ORF consisting of 549 nt at the 1960 to 1412 and
      deduced 182 amino acids was found in SF02. The SF02 genome shared 83% identity
      and its 6 ORFs 81.9-86.1% identities with the reference APMV-1 strains. The
      possible mechanism determining different host range and pathogenicity is
      discussed based on genetic analyses.

PMID- 15744559
TI  - Functional variability of Rev response element in HIV-1 primary isolates.
AB  - We have previously studied sequence heterogeneity of HIV-1 Rev response element
      (RRE), and showed uneven variations in different stem-loops of both primary
      sequence and secondary structure. Here we studied the functional variation of RRE
      clones from a set of 10 primary isolates, and demonstrated a variation in the
      function of these RRE clones on the expression of Gag proteins from a truncated
      HIV-1 genome. The difference in Gag level was, in part, if not exclusively,
      resulted from the differential efficiency of RNA transport and enhancing of
      translation. These data suggested that variation of HIV-1 RRE may play a role in
      regulation of viral replication rate in HIV-1 primary isolates.

PMID- 15744560
TI  - Cervical cancer-causing human papillomaviruses have an alternative initiation
      site for the L1 protein.
AB  - All known sequences of the DNA encoding the major cervical cancer-causing human
      papillomavirus type 16 (HPV16) L1 capsid protein contain initiation codons which
      would allow translation to begin at either nucleotide 5559 or 5637. However the
      formation of virus-like particles (VLPs) only occurs efficiently when the
      initiation codon at nucleotide 5637 is used for in vitro expression studies. This
      knowledge, in concert with the fact that virions have not been observed in HPV16
      infected epithelium, raises the notion that the major L1 translation product in
      this HPV type may be largely confined to initiation at nucleotide 5559. Sequence
      analysis of various HPV types associated with particular clinical outcomes has
      revealed that L1 sequences of the major cervical cancer-associated viruses
      generally possess the ability to encode a longer translation product whilst the
      non-cancer-causing viruses do not. Equally intriguing, the upstream initiation
      codon is always separated by 78 nucleotides from the initiation codon that
      produces L1 protein which efficiently assembles into VLPs. We speculate that the
      longer L1 protein could play a role in the development of cervical carcinoma and
      that HPVs with the potential to cause cervical cancer may be identified by the
      presence of an in-frame ATG situated 78 nucleotides upstream.

PMID- 15744561
TI  - Nucleocapsid protein of cell culture-adapted Seoul virus strain 80-39: analysis
      of its encoding sequence, expression in yeast and immuno-reactivity.
AB  - Seoul virus (SEOV) is a hantavirus causing a mild to moderate form of hemorrhagic
      fever with renal syndrome that is distributed mainly in Asia. The nucleocapsid
      (N) protein-encoding sequence of SEOV (strain 80-39) was RT-PCR-amplified and
      cloned into a yeast expression vector containing a galactose-inducible promoter.
      A survey of the pattern of synonymous codon preferences for a total of 22 N
      protein-encoding hantavirus genes including 13 of SEOV strains revealed that
      there is minor variation in codon usage by the same gene in different viral
      genomes. Introduction of the expression plasmid into yeast Saccharomyces
      cerevisiae resulted in the high-level expression of a hexahistidine-tagged N
      protein derivative. The nickel-chelation chromatography purified, yeast-expressed
      SEOV N protein reacted in the immunoblot with a SEOV-specific monoclonal antibody
      and certain HTNV- and PUUV-cross-reactive monoclonal antibodies. The immunization
      of a rabbit with the recombinant N protein resulted in the induction of a high
      titered antibody response. In ELISA studies, the N protein was able to detect
      antibodies in sera of experimentally infected laboratory rats and in human anti
      hantavirus-positive sera or serum pools of patients from different geographical
      origin. The yeast-expressed SEOV N protein represents a promising antigen for
      development of diagnostic tools in serology, sero prevalence studies and vaccine
      development.

PMID- 15744562
TI  - Viral sequence insertions and a novel cellular insertion in the NS2 gene of
      cytopathic isolates of bovine viral diarrhea virus as potential cytopathogenicity
      markers.
AB  - Cytopathogenicity of bovine viral diarrhea virus (BVDV) has been shown to
      correlate with the presence of insertions of cellular sequences, duplication of
      viral sequences with or without insertions, deletions, and point mutations in the
      genomes of cytopathogenic (cp) strains. In the present study we have investigated
      cytopathogenicity markers in the genomes of six cp BVDV isolates. The viruses
      were selected as representatives of various forms of BVDV infection, in some
      cases presumably induced by vaccination with a live attenuated vaccine. The
      complete NS2-3 coding region of the six isolates and of the vaccine virus were
      amplified by reverse transcription-polymerase chain reaction (RT-PCR) and
      sequenced. In the genomes of four isolates (H6379, H6712, H8427 and H-BVD MD) and
      of the vaccine virus, a 45-nucleotide viral insertion was found at nucleotide
      position 4355, encompassing nucleotides 8402-8446, that encode 15 amino acids of
      the NS4B/NS5A junction region in a normal BVDV genome. Isolate H3887 had a 21
      nucleotide insertion of non-viral origin, also located at nucleotide position
      4355. This insertion has a high homology with a gene coding for murine interferon
      induced guanylate-binding protein 1, and represents the first non-viral insertion
      identified at this position of the NS2 coding region. Isolate H3142 carries a 42
      nucleotide insertion at position 4361, identical to a part of the NS5B gene
      mapping to position 11078-11119. Additionally, this isolate also has a deletion
      of three nucleotides (positions 4448-4450). The role of the 45-nucleotide
      insertion in expression of NS3 was investigated using the vaccine virus. The NS2
      3 gene of this virus, and that of a generated insertion-negative variant were
      cloned in the mammalian expression vector pCI, and expressed in bovine turbinate
      cells. Western blot analysis revealed that the insertion contributed to a partial
      cleavage of NS2-3 generating NS3, the marker protein for cytopathogenicity in
      BVDV. The genome rearrangements found in these isolates occurred preferentially
      at position 4355, suggesting that this part of the genome could represent a
      potential hot spot for recombination events in ncp BVDV. The molecular mechanism
      underlying this phenomenon, however, remains to be elucidated.

PMID- 15744563
TI  - Variable regions 1 and 2 (VR1 and VR2) in JSRV gag are not responsible for the
      endogenous JSRV particle release defect.
AB  - Jaagsiekte sheep retrovirus (JSRV) is a betaretrovirus causing ovine pulmonary
      adenocarcinoma, a transmissible lung tumor of sheep. A very closely related
      endogenous retrovirus (enJSRV) occurs as 15 to 20 copies in the genome of all
      sheep, and is not known to be linked to pathogenesis. We previously localized a
      particle release defect of the full-length endogenous-derived expression
      construct pCMV2enJS56A1 to the amino-terminal region of gag that incorporates the
      two variable regions VR1 and VR2, which harbor the main sequence differences
      between endogenous and exogenous JSRV in this part of gag. Here, we tested the
      hypothesis that either or both of these variable regions are responsible for the
      observed particle release defect in enJS56A1. We found that the PPPPPPPS motif of
      the exogenous VR1 is neither necessary nor sufficient for particle release.
      Furthermore, the precise substitution of VR1 and VR2 in the exogenous JSRV
      expression plasmid pCMV2JS21, using their enJS56A1-derived counterparts, did not
      abrogate the ability of the resulting constructs to release particles. The
      particle release defect of enJS56A1 is therefore not determined exclusively by
      either VR1 or VR2. These results point to a small number of amino acids lying
      outside of VR1 and VR2 that may be responsible for the particle defect of
      enJS56A1 Gag.

PMID- 15744564
TI  - Cloning and sequence analysis of the M gene of porcine epidemic diarrhea virus
      LJB/03.
AB  - Porcine epidemic diarrhea virus (PEDV) LJB/03 was isolated from the fece of
      piglets infected with PEDV on a pig farm, Heilongjiang province, China. The M
      gene of LJB/03 was amplified from the RNA extracted directly from the fece
      samples by RT-PCR and cloned into pMD18-T vector. The M gene cDNA was sequenced
      and encompasses an open reading frame of 681 nucleotides, encoding a 226-amino
      acid protein. The LJB/03 M gene has a base composition of 152 adenines (22%), 153
      cytosines (23%), 161 guanines (24%), and 214 thymines (31%). Sequence comparison
      with other PEDV strains selected from GenBank revealed that the LJB/03 M gene has
      a high sequence homology to those of other PEDV isolates, 97.80% with JMe2,
      96.92% with KPEDV-9 (Korean field isolate), 97.36% with KPEDV-9 (Korean), 97.80%
      with Br1/87, and 97.94% with CV777. The encoded protein shared 97.79% amino acid
      identities compared with CV777, 97.35% with Br1/87, 97.79% with JMe2, 96.90% with
      KPEDV-9 (Korean field isolate), 96.46% with KPEDV-9 (Korean). Sequence analysis
      of the M gene, including genetic distance measurement, phylogenetic tree
      analysis, and residue substitution analysis, showed that all other PED viruses
      analyzed fell into three groups, and the LJB/03 itself branched in an independent
      group. These data revealed that the M gene nucleotide sequence of LJB/03 has some
      mutations in comparison with the other PED viruses.

PMID- 15744565
TI  - Identification of a naturally occurring recombinant isolate of Sugarcane mosaic
      virus causing maize dwarf mosaic disease.
AB  - The complete nucleotide sequence of a potyvirus causing severe maize dwarf mosaic
      disease in Shaanxi province, northwestern China was determined (GenBank accession
      No. AY569692). The full genome is 9596 nucleotides in length excluding the 3 '
      terminal poly (A) sequence. It contains a large open reading frame (ORF) flanked
      by a 149 nt 5'-untranslated region (UTR) and a 255 nt 3'-UTR. The putative
      polyprotein encoded by this large ORF comprises of 3063 amino acid residues.
      Sequence comparisons and phylogenetic analyses showed that this potyvirus is an
      isolate of Sugarcane mosaic virus (SCMV). The entire sequences shared identities
      of 89.6-97.6 % and 79.3-93.3% with 9 sequenced SCMV isolates at the nucleotide
      and deduced amino acid levels, respectively. But it showed much lower identities
      with Maize dwarf mosaic virus (MDMV), Sorghum mosaic virus (SrMV) and
      Johnsongrass mosaic virus (JGMV) isolates. The putative coat protein sequence is
      identical to that of a Chinese maize isolate SCMV-HZ. However, partition
      comparisons and phylogenetic profile analyses of the viral nucleotide sequences
      indicated that it is a recombinant isolate of SCMV. The recombination sites are
      located within the 6K1 and CI coding regions.

PMID- 15744566
TI  - Molecular cloning of coat protein gene of an Indian cotton leaf curl virus (CLCuV
      HS2) isolate and its phylogenetic relationship with others members of
      Geminiviridae.
AB  - Cotton leaf curl geminivirus is a whitefly (Bemisia tabaci Genn.) transmitted
      Begomovirus (Family Geminiviridae) causing a serious disease of cotton in
      northern India. The very typical symptoms of present isolate (CLCuV-HS2) showed
      thickened veins, dark green discoloration of the leaves with upward curling and
      leaf like structure known as enation (one in number), which develops into cup
      shaped on the reverse side of leaves. The polymerase chain reaction (PCR) based
      technique can detect the viral DNA in samples stored upto 3 days after the
      collection and have wide application for the field diagnosis. The complete
      nucleotide sequence of the Indian isolate of cotton leaf curl geminivirus (CLCuV
      HS2) coat protein (CP) gene component was determined using CP specific primers
      through PCR amplification from field infected cotton plants growing in Haryana,
      India. Comparison of the amino acid sequence of the putative CP with some other
      mono and bipartite geminiviruses revealed a maximum of 97.3% identity with
      Pakistan cotton leaf curl virus (CLCuV-62). A nuclear localization signal located
      close to the N-terminal of CP gene was determined.

PMID- 15744567
TI  - Isolation of virus from a SARS patient and genome-wide analysis of genetic
      mutations related to pathogenesis and epidemiology from 47 SARS-CoV isolates.
AB  - Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus
      (SARS-CoV) is a fatal disease. Prevention of future outbreaks is essential and
      requires understanding pathogenesis and evolution of the virus. We have isolated
      a SARS-CoV in China and analyzed 47 SARS-CoV genomes with the aims to reveal the
      evolution trends of the virus and provide insights into understanding
      pathogenesis and SARS epidemic. Specimen from a SARS patient was inoculated into
      cell culture. The presence of SARS-CoV was determined by RT-PCR and confirmed by
      electron microscopy. Virus was isolated followed by the determination of its
      genome sequences, which were then analyzed by comparing with other 46 SARS-CoV
      genomes. Genetic mutations with potential implications to pathogenesis and the
      epidemic were characterized. This viral genome consists of 29,728 nucleotides
      with overall organization in agreement with that of published isolates. A total
      of 348 positions were mutated on 47 viral genomes. Among them 22 had mutations in
      more than three genomes. Hot spots of nucleotide variations and unique trends of
      mutations were identified on the viral genomes. Mutation rates were different
      from gene to gene and were correlated well with periodical or geographic
      characteristics of the epidemic.

PMID- 15744568
TI  - Cumulative mutations in the genome of Echovirus 6 during establishment of a
      chronic infection in precursors of glial cells.
AB  - Although Enteroviruses are mainly described as responsible for acute diseases,
      their role in severe chronic pathology has been also established. Echovirus 6
      like sequences have been detected by PCR analysis in central nervous system
      specimens from patients presenting with Amyotrophic Lateral Sclerosis. These
      findings suggested a persistent infection with viruses that underwent, genetic
      changes precluding viral particle release. To support this hypothesis, we
      developed a model system of Echovirus 6 chronic infection in precursors of glial
      cells. The nucleotide sequences of the 5'non-translated region (5'NTR), 2A and 3C
      regions of the virus developing persistent genome were analysed during
      establishment of the chronic phenotype. This study revealed that at day 160 of
      chronic infection, several mutations were observed: one mutation at nucleotide
      108 upstream the domain II of the internal ribosome entry site (IRES) structure,
      one mutation at nucleotide 30 in the cloverleaf, and two mutations in the 2A
      region (translated in His48 to Tyr, and Ile 123 to Met). No mutations were
      detected in the 3C region. The impact of these mutations on viral replication
      have been analysed in a rabbit reticulocyte lysate (RRL) translation assay
      supplemented with HeLa cell lysate, and by plaque assay. Viruses with these
      mutations displayed a phenotype with a significant reduction of replication,
      while in vitro translation was not affected by the nucleotide 108 mutation. This
      model allowed the description of molecular changes observed in the genome of
      Echovirus 6 during the establishment of a chronic infection phenotype, and may be
      helpful for the understanding of the mechanisms leading Enteroviruses to develop
      chronic infections in man.

PMID- 15744569
TI  - Completion of the sequence of a cetacean morbillivirus and comparative analysis
      of the complete genome sequences of four morbilliviruses.
AB  - The gene encoding the large (L) protein and the genome termini of the dolphin
      strain of cetacean morbillivirus (CeMV) were sequenced. The CeMV genome is 15702
      nucleotides long and has been compared with other available morbillivirus genome
      sequences in regards to the "rule of six" and the "phase" of any particular
      nucleotide, defined as its position within a given hexamer, which here is defined
      as a group of six nucleotides starting from the 3' end of the genomic RNA. With
      exception of the position of the start of the F gene, the phase of the
      transcription start sites of each gene is strictly conserved between the
      morbilliviruses, but each gene is in a different phase. The lengths of gene
      transcripts differ between viruses by multiples of six nucleotides with exception
      of the M and F transcripts. The differences between the various morbilliviruses
      result from deletions or insertions of multiples of six nucleotides in the 3' and
      5' UTRs of the different viral genes. The four bases were distributed non
      randomly over the six positions in the hexamer boxes. However, the distribution
      patterns of each of the four bases indicated that multiples of three were more
      prevalent than those of six nucleotides. This reflected the positions of
      nucleotides in codons and codon usage in the reading frames. The L protein of
      CeMV was found to be 2183 amino acids in length and similar to that of MV and
      RPV. The CeMV L protein sequence was found to be equidistant between those of the
      CDV/PDV and MV/RPV subgroups of the morbilliviruses. This concurs with the
      analyses carried out on the other structural proteins.

PMID- 15744570
TI  - Binding of cellular proteins to the leader RNA of equine arteritis virus.
AB  - The genome of equine arteritis virus (EAV) produces a 3' coterminal-nested set of
      six subgenomic (sg) viral RNAs during virus replication cycle, and each set
      possesses a common leader sequence of 206 nucleotides (nt) in length derived from
      the 5' end of the viral genome. Given the presence of the leader region within
      both genomic and sg mRNAs, it is likely to contain cis-acting signals that may
      interact with cellular or viral proteins for RNA synthesis. Gel mobility shift
      assays indicated that proteins in Vero cell cytoplasmic extracts formed complexes
      with the positive (+) and negative (-) strands of the EAV leader RNA. Several
      cell proteins with molecular masses ranging from 74 to 31 kDa and 58 to 32 kDa
      were detected in UV-induced cross-linking assays with the EAV leader RNA (+) and
      (-) strands, respectively. In both cases, intense bands were observed at the 58
      52 kDa molecular weight markers. Results from competition gel mobility shift
      assays using overlapping cold RNA probes spanning the leader RNA (+) strand
      indicated that nt 140-206 are not necessary for binding to cell proteins.

PMID- 15744571
TI  - A point of view: HIV-1/AIDS is an allergy but CpG ODN treatments may inhibit
      virus replication and reactivate the adaptive immunity--hypothesis and
      implications.
AB  - Reevaluation of the increase in the levels of IgE and IL-4 in sera of HIV-1
      infected and AIDS patients led to the suggestion that AIDS resembles allergy.
      Studies on the properties of the viral shed gp120 revealed that it resemble
      environmental allergens in their ability to induce hematopoietic cells to release
      large amounts of Th2 cytokines, inhibitors of the patients adaptive immune
      response. Yet, induction of TLR9+ plasmacytoid DCs by CpG ODNs cause the release
      of type I interferons, inhibitors of HIV-1 replication and IL-4 release from
      hematopoietic cells. CpG ODN binding to TLR+ B cells inhibits IgE synthesis and
      reactivates the failing adaptive immunity. The possible use of CpG ODNs as
      treatment to patients is discussed.

PMID- 15744572
TI  - The function of envelope protein P74 from Autographa californica multiple
      nucleopolyhedrovirus in primary infection to host.
AB  - This research investigated the function of envelope protein P74 of Autographa
      californica multiple nuclear polyhedrosis virus (AcMNPV) in primary infection to
      host. A p74-inactivation recombinant baculovirus, rAc-gfp(Delta) p74, was
      constructed by inserting gfp driven by AcMNPV polyhedrin promoter into the p74
      locus of AcMNPV genome. Bioassays showed that the P74-null occlusion bodies (OBs)
      failed to infect its natural host larvae, Spodoptera exigua, per os, while the
      p74-null budded virus (BVs) could infect host larvae by injection. However, its
      inability for oral infectivity was rescued by a mixed infection with wild-type
      OBs or with the purified P74 protein expressed in Spodoptera frugiperda Sf-9
      cells, and the P74 protein rescue was in a dosage-dependent manner. The 50%
      lethal dosage (LD50) value of a P74 overexpression recombinant virus, rAc-p74(++)
      polh+, which contained two copies of p74 gene, was not significantly different
      from that of wild-type virus. One-step growth curve assays of viruses suggested
      that BV production from cells infected with p74-null virus was similar to that
      from cells infected with wild-type virus or the P74 overexpression virus. ELISA
      analysis indicated that P74 protein could bind its host brush border membrane
      vesicles (BBMV) efficiently with saturation, but it could only bind its sensitive
      midgut BBMV specifically. In vitro pull-down assay showed that a protein of
      approximately 35 kDa in the BBMV was involved in the specific binding. These
      results demonstrated that the P74 protein is essential for oral infectivity of
      occlusion-derived virus (ODV) and plays a role in midgut attachment and fusion.

PMID- 15744573
TI  - Analysis of the virus population present in equine faeces indicates the presence
      of hundreds of uncharacterized virus genomes.
AB  - Virus DNA was isolated from horse faeces and cloned in a sequence-independent
      fashion. 268 clones were sequenced and 178140 nucleotides of sequence obtained.
      Statistical analysis suggests the library contains 17560 distinct clones derived
      from up to 233 different virus genomes. TBLASTX analysis showed that 32% of the
      clones had significant identity to GenBank entries. Of these 63% were viral; 20%
      bacterial; 7% archaeal; 6% eukarya; and 5% were related to mobile genetic
      elements. Fifty-two percent of the virus identities were with Siphoviridae; 26%
      unclassified phages; 17% Myoviridae; 4% Podoviridae; and one clone (2%) was a
      vertebrate Orthopoxvirus. Genes coding for predicted virus structural proteins,
      proteases, glycosidases and nucleic acid-binding proteins were common.

PMID- 15744575
TI  - The conserved, 5' termini of RNAs 1 and 2 of Tomato aspermy virus are dispensable
      for infection but affect virulence.
AB  - The 5' terminus of each of the three genomic RNAs (RNAs 1, 2 and 3) of Tomato
      aspermy virus (TAV) begins with the sequence 5'-GUUU, which is also shared by a
      number of other viruses. Mutagenic analyses showed that the 5'-GUUU sequence of
      RNAs 1 and 2 of TAV was dispensable for viral infection and did not prevent
      symptom induction. On the other hand, substitution of U at position 5 for G in
      RNA 1, but not RNA 2, induced veinal necrosis symptoms in Nicotiana glutinosa.
      The mutants constructed included insertion of UUU into the 5'-GUUU sequence of
      TAV RNAs 1 and/or 2. All RNA 2 mutants induced more severe symptoms than viral
      RNAs containing either mutated RNA 1 or most combinations of mutated RNAs 1 and
      2. Some combinations of mutated RNAs 1 and 2 also induced veinal necrosis in N.
      glutinosa. Virulence was unrelated to the levels of viral RNA accumulation.
      Sequence analysis of progeny viral RNAs showed that only the mutant viral RNAs
      with a G to U substitution in RNA 1 and the deletion of the 5'-GUUU in both RNAs
      1 and 2 were able to maintain the same sequence as the inoculum. The other
      mutants either reverted to the wildtype sequence or underwent further deletion or
      insertion. None of the constructed mutants were able to compete for accumulation
      with the wildtype virus after co-inoculation to the plant species tested.

PMID- 15744576
TI  - Comparative analysis of the prion protein open reading frame nucleotide sequences
      in peacock and parakeet.
AB  - The open reading frame of peacock and parakeet prion protein (PrP) genes was
      cloned and sequenced. The peacock and parakeet PrP genes consisted of 833 and 866
      nucleotides encoding 266 and 277 amino acids, respectively (GenBank Accession
      numbers AY365065 and AY365066). Sequence analysis showed that the peacock and
      parakeet PrP genes had 93.67% homology to each other, 94.04% and 99.64% homology
      to the chicken PrP gene and 46.0% and 42.1% similarity to the mammalian PrP
      genes, respectively. The structural features of all known mammalian and avian
      PrPs, including N-terminal signal peptides, tandem repeats, conserved hydrophobic
      region, disulfide bridges and glycoinositol phospholipid anchor, were also found
      in peacock and parakeet PrPs. The parakeet and peacock PrPs, however, differed in
      the hexarepeat region, with the peacock having six and the parakeet having seven
      hexarepeats. The phylogenetic analysis showed that the PrP genes in 52 species
      were clustered into 2 distinct lineages, the avian and the mammalian. The peacock
      and parakeet PrP genes belonged to the same lineage but the peacock PrP was sub
      classed with the pigeon PrP and the parakeet PrP was sub-classed with the duck
      and chicken PrPs. The present work added two more species data to the collection
      of the PrP genes and supported the previous findings that the PrP genes are
      highly conserved across species.

PMID- 15744577
TI  - Temperature sensitive mutation in the 38 kDa minor structural protein gene of
      phage MB78 interferes with phage morphogenesis.
AB  - Temperature sensitive mutation in the gene for the 38 kDa minor structural
      protein of the phage MB78, a virulent phage of Salmonella enterica serovar
      typhimurium, interferes with phage development at restrictive temperature.
      Electron microscopy of particles produced at non-permissive temperature indicated
      that the particles formed are tailless. Two types of particles are seen: (i)
      empty capsids, which are not perfect icosahedral (ii) icosahedral particles
      filled with DNA. The gene for the 38 kDa protein is located in the SalIG fragment
      of the phage genome. Nucleotide sequence of the SalIG fragment of MB78 as well as
      its temperature sensitive mutant has been determined and analysed. Such analysis
      indicated that in the mutant the codon GCA has been changed to GTA resulting in
      substitution of alanine at position 75 of the protein by valine (A75V). This
      makes the protein thermolabile. Our results suggest that normal functioning of
      this 38 kDa protein is necessary for attachment of tail fibre to the capsid. Or
      in other words, this 38 kDa protein is involved in phage morphogenesis.

PMID- 15744574
TI  - New ecological aspects of hantavirus infection: a change of a paradigm and a
      challenge of prevention--a review.
AB  - In the last decades a significant number of so far unknown or underestimated
      pathogens have emerged as fundamental health hazards of the human population
      despite intensive research and exceptional efforts of modern medicine to embank
      and eradicate infectious diseases. Almost all incidents caused by such emerging
      pathogens could be ascribed to agents that are zoonotic or expanded their host
      range and crossed species barriers. Many different factors influence the status
      of a pathogen to remain unnoticed or evolves into a worldwide threat. The ability
      of an infectious agent to adapt to changing environmental conditions and
      variations in human behavior, population development, nutrition, education,
      social, and health status are relevant factors affecting the correlation between
      pathogen and host. Hantaviruses belong to the emerging pathogens having gained
      more and more attention in the last decades. These viruses are members of the
      family Bunyaviridae and are grouped into a separate genus known as Hantavirus.
      The serotypes Hantaan (HTN), Seoul (SEO), Puumala (PUU), and Dobrava (DOB) virus
      predominantly cause hemorrhagic fever with renal syndrome (HFRS), a disease
      characterized by renal failure, hemorrhages, and shock. In the recent past, many
      hantavirus isolates have been identified and classified in hitherto unaffected
      geographic regions in the New World (North, Middle, and South America) with
      characteristic features affecting the lungs of infected individuals and causing
      an acute pulmonary syndrome. Hantavirus outbreaks in the United States of America
      at the beginning of the 10th decade of the last century fundamentally changed our
      knowledge about the appearance of the hantavirus specific clinical picture,
      mortality, origin, and transmission route in human beings. The hantavirus
      pulmonary syndrome (HPS) was first recognized in 1993 in the Four Corners Region
      of the United States and had a lethality of more than 50%. Although the causative
      virus was first termed in connection with the geographic name of its outbreak
      region the analysis of the individual viruses indicate that the causing virus of
      HPS was a genetically distinct hantavirus and consequently termed as Sin Nombre
      virus. Hantaviruses are distributed worldwide and are assumed to share a long
      time period of co-evolution with specific rodent species as their natural
      reservoir. The degree of relatedness between virus serotypes normally coincides
      with the relatedness between their respective hosts. There are no known diseases
      that are associated with hantavirus infections in rodents underlining the
      amicable relationship between virus and host developed by mutual interaction in
      hundreds of thousands of years. Although rodents are the major reservoir,
      antibodies against hantaviruses are also present in domestic and wild animals
      like cats, dogs, pigs, cattle, and deer. Domestic animals and rodents live
      jointly in a similar habitat. Therefore the transmission of hantaviruses from
      rodents to domestic animals seems to be possible, if the target organs, tissues,
      and cell parenchyma of the co-habitat domestic animals possess adequate virus
      receptors and are suitable for hantavirus entry and replication. The most likely
      incidental infection of species other than rodents as for example humans turns
      hantaviruses from harmless to life-threatening pathogenic agents focusing the
      attention on this virus group, their ecology and evolution in order to prevent
      the human population from a serious health risk. Much more studies on the
      influence of non-natural hosts on the ecology of hantaviruses are needed to
      understand the directions that the hantavirus evolution could pursue. At least,
      domestic animals that share their environmental habitat with rodents and humans
      particularly in areas known as high endemic hantavirus regions have to be
      copiously screened. Each transfer of hantaviruses from their original natural
      hosts to other often incidental hosts is accompanied by a change of ecology, a
      change of environment, a modulation of numerous factors probably influencing the
      pathogenicity and virulence of the virus. The new environment exerts a modified
      evolutionary pressure on the virus forcing it to adapt and probably to adopt a
      form that is much more dangerous for other host species compared to the original
      one.

PMID- 15744578
TI  - Molecular cloning, DNA sequence analysis, and expression of cDNA sequence of RNA
      genomic segment 6 (S6) that encodes a viral outer capsid protein of threadfin
      aquareovirus (TFV).
AB  - The genome segment 6 (S6) of threadfin reovirus (TFV) was cloned and sequenced.
      The entire S6 nucleotide sequence is 2056 bp long with an open reading frame that
      encodes a protein of 653 amino acids. Sequence analysis of the TFV S6 genome
      revealed that the 5'-terminal sequence, GTTTTA and the 3'-terminal sequence,
      ATTCATC of the plus strand is common to other genome segments of TFV. The
      pentanucleotide, TCATC, at the 3'-terminal of the plus strand was also conserved
      in other reported isolates of Aquareovirus such as chum salmon reovirus (CSV),
      striped bass reovirus (SBR), grass carp reovirus (GCRV) and golden shiner
      reovirus (GSV) as well as to the 10 genome segments of mammalian reovirus (MRV).
      Blast results indicated that the TFV S6 gene segment sequence had high identity
      towards the CSV S6 gene sequence, which codes for the CSV outer coat protein.
      This implied that the TFV S6 gene segment codes for an outer capsid protein (OCP)
      of the virus. Amino acid sequence analysis of this TFV OCP sequence revealed the
      presence of a putative conserved asparagine-proline (Asn-Pro) protease cleavage
      site, which was found in all reported isolates of Aquareovirus as well as in the
      MRV mu1 protein. N-terminal sequencing of the corresponding S6 native protein
      obtained from purified TFV particles verified the presence of this cleavage site.
      Phylogenetic analysis of the TFV S6 protein revealed that TFV was closely related
      to CSV, from Aquareovirus species, ARV-A. Cloning of the TFV S6 gene sequence
      into an Escherichia coli expression host produced a recombinant protein that
      corresponded to the predicated size of the OCP of TFV. Immunization of mice using
      this recombinant outer capsid protein (rOCP) revealed that the protein was able
      to elicit an antibody response, thus indicating that the rOCP of TFV was
      immunogenic.

PMID- 15744579
TI  - Nucleotide sequences and functions of the Epstein-Barr virus latent membrane
      protein 1 genes isolated from salivary gland lymphoepithelial carcinomas.
AB  - Epstein-Barr virus (EBV) infection is associated with salivary gland
      lymphoepithelial carcinoma (SLEC) and nasopharyngeal carcinoma (NPC). EBV is a
      ubiquitous herpes virus world wide, but EBV-associated SLEC and NPC are prevalent
      in restricted regions such as south areas of China, Southeastern Asia and
      Greenland (Eskimos). To examine whether particular EBV variants play roles in the
      development of SLEC and NPC, we isolated the complete EBV LMP1 genes from 12
      paraffin-embedded biopsy samples of SLECs isolated from China, Taiwan and Russia,
      and compared these LMP1 genes with those of NPC (CAO) and the prototype B95-8
      EBV. Nucleotide sequence analysis showed that SLECs LMP1 is more similar to that
      of CAO than that of prototype B95-8. The analysis also identified several
      conserved (67-100%) variations in SLEC-LMP1 and CAO-LMP1 distinct from B95-8
      LMP1. These included 10-amino acid deletion, 5-amino acid deletion and 12-single
      amino acid variations. A SLEC-LMP1 gene with the aforementioned conserved
      variations inhibited the growth of an embryonic kidney cell line (293T), highly
      activated the NF-kappaB pathway, and these activities were equivalent to those of
      B95-8 and CAO. These findings suggest that the biological functions of SLEC-LMP 1
      are similar to those of B95-8-LMP1 and CAO-LMP1, and that these amino acid
      variations including the well-known 10-aa deletion did not affect these two
      prominent activities. While the present results could not uncover functional
      differences between SLEC-LMP1 and B95-8-LMP1, the nucleotide sequences and the
      molecular clone of LMP1 directly isolated from SLEC patients will be a useful
      tool to identify the high-pathogenic EBV strain(s), associated with SLEC and NPC.

PMID- 15744580
TI  - Complete sequence of the RNA genome of pneumonia virus of mice (PVM).
AB  - Pneumonia virus of mice (PVM) is an enveloped RNA-containing virus of Family
      Paramyxoviridae. Sequences had been determined previously for a number of PVM
      genes, although these represented cloned cDNAs rather than consensus sequences.
      Sequences were not available for the 3' -leader and 5' -trailer regions that
      constitute the genome termini or for the large polymerase L gene that accounts
      for 43% of the genome. Also, the available sequences were from an attenuated
      variant of strain 15, whereas the present study analyzed the version of strain 15
      that is available from the American Type Culture Collection (ATCC) and is highly
      virulent in mice. Analysis of unclosed RT-PCR products yielded a complete
      consensus sequence of 14,886 nt (GenBank accession number AY729016). Of the
      regions for which sequences had been previously reported for the non-pathogenic
      strain, there were 13 nucleotide differences and 10 amino acid differences
      compared to the present consensus sequence for the virulent isolate. The various
      genes of PVM shared 29-62% nucleotide sequence identity and 10-60% amino acid
      sequence identity with human or bovine respiratory syncytial virus (HRSV and
      BRSV), its closest relatives.

PMID- 15744581
TI  - CpG ODNs treatments of HIV-1 infected patients may cause the decline of
      transmission in high risk populations - a review, hypothesis and implications.
AB  - The Joint United Nations Program on HIV-1/AIDS (UNAIDS) announced its goal to
      stop HIV-1 transmission by antiviral (HAART) treatment of patients since at the
      end of 2003 the number of people living with HIV-1 was 38 million, 25 million in
      the sub-Saharan region of Africa. The present review deals with a new approach to
      simultaneously treat HIV-1/AIDS patients in HIV-1 endemic regions with CpG
      oligodeoxynucleotides (ODNs) and people at high risk of infection with a vaccine
      containing CpG ODNs combined with synthetic HIV-1 peptides by intranasal and
      intradermal applications. During HIV-1 infection a gradual increase in the levels
      of IL-4 and IgE in the patients' serum, was reported. It was suggested that such
      an increase of the cytokine IL-4 and the IgE immunoglobulin are interconnected
      and may serve as indicators for the coming stage of AIDS. It was also suggested
      that the IL-4 and IgE increase in the serum of HIV-1 infected people resemble the
      increase of IL-4 and IgE levels in allergic patients that were exposed to
      endogenous or environmental allergens [Becker, Virus Genes 28, 5--18, 2004].
      Indeed, it was reported that the HIV-1 virions' shed gp120 molecules, which
      contain a superantigen (superallergen) domain that enables the viral glycoprotein
      to bind the V(H)3 domain of IgE molecules that are bound to FcepsilonRI+
      hematopoietic cells [basophils, mast cells, dendritic cells (DCs) and
      plasmacytoid DCs (pDCs)]. Such interaction was reported to induce the
      hematopoietic cells to release large amounts of Th2 cytokines IL-4, IL-5, IL-10
      and IL-13. These findings led to the hypothesis [Op. cit.] that the cure of HIV
      1/AIDS patients requires the induction of endogenous synthesis of type I
      interferons (INF alpha and beta) with a bacterial CpG rich DNA that will induce
      the patients' pDCs to release large amounts of type I IFNs. Under these
      conditions HIV-1 replication in polarized to Th2 cells is inhibited. Type I IFNs
      reactivate the patients' inhibited Th1 cells to synthesize IL-2 and IL-12
      cytokines that activate the maturation of CTL precursors. The unmethylated
      bacterial DNA activates B synthesis to switch to IgG and IgA synthesis. The novel
      drug CpG ODNs is being tested for the prevention and the treatment of allergic
      humans and in the experimental system of allergic mice. It was also reported that
      treatment of mice with CpG ODN prior to or after retrovirus infections protected
      and cured, respectively, the retrovirus infection. It was also reported that CpG
      ODNs treatments of mice exposed to allergen protected them against the
      development of the allergic response. Phase I treatment of healthy people with
      CpG ODNs provided information on the safety of these compounds. The CpG ODNs A
      and B bind to Toll like receptors that are present in pDCs and B cells,
      respectively, CpG ODN - A is the ligand for TLR9+ pDCs and induce the release of
      large amounts of IFN-alpha, beta. CpG ODN-B is the ligand for TLR9+ in B cells
      and induce the synthesis of IgG and IgA. CpG ODN-C contains motifs from CpG ODNs
      A and B and is more active. The present review is based on findings from studies
      that reported that CpG ODNs treatment of retrovirus infected mice, monkeys and
      allergic mice prevented the virus and allergens caused diseases, respectively.
      Based on these studies, a hypothesis is presented that treatment of HIV-1
      infected and AIDS patients with CpG ODN-A and B or CpG ODN-C have the potential
      to inhibit IL-4 synthesis and release from FcrepsilonRI+ hematopoietic cells by
      inducing TLR9+ pDCs to release large amounts of type I IFNs. TLR9+ B cells are
      induced by CpG ODN-B to switch from IgE to IgG, IgA synthesis. In addition, type
      I IFNs (alpha, beta) have the capacity to inhibit HIV-1 replication in polarized
      Th2 cells. Type I IFNs reactivate the patients' Th1 cells to synthesize IL-2 and
      IL-12 cytokines, activators of the precursor cytotoxic T cells (CTLs), leading to
      the reactivation of the inhibited adaptive immune response. Antiviral CTLs have
      the ability to clear the virus infection. The present novel approach to the
      treatment and of HIV-1/AIDS patients with CpG ODNs may prevent HIV-1 transmission
      and the AIDS pandemic if controlled studies on the treatments with CpG ODNs of
      HIV-1 infected people will be done by international and private agencies and
      companies to define the effective treatment regime and the efficacy of the
      treatments to HIV-1 infected people at different times post-infection. It is also
      hypothesized that in order to stop HIV-1 transmission in HIV-1 endemic regions
      the people at high risk of HIV-1 infection should be treated at the same time as
      HIV-1 infected people with a vaccine containing synthetic CpG-ODNs combined with
      synthetic HIV-1 peptides, compatible with the major HLA haplotypes of the
      regional population. The vaccine may be self-applied by people at high risk of
      infection by the intra-nasal route and by intra-dermal application as a
      "peplotion vaccine". The stimulation of the antiviral CTL response by HIV-1
      infected people and the active antiviral immune response in the vaccinated
      population may lead to a decline in HIV-1 transmission and may be a model for
      control of the HIV-1/AIDS pandemic.

PMID- 15744582
TI  - Amino acid variation within the fusion protein of respiratory syncytial virus
      subtype A and B strains during annual epidemics in South Africa.
AB  - Recent evidence of positive selection within the cytotoxic T-cell (CTL) epitopes
      of the highly conserved nucleoprotein of influenza virus raised the question of
      whether the CTL epitopes of Respiratory syncytial virus (RSV) are also affected
      by immune driven change over annual epidemics. The fusion protein (F-protein) of
      RSV is highly conserved within the two subtypes (A and B) and the most important
      target for the protective response. The position of various neutralizing epitopes
      has been mapped and characterized between RSV subtypes. CTL epitopes have also
      recently been mapped for the F-protein of subtype A, however variation within
      these epitopes between and within the subtypes has not been determined. To
      address this question, the F-proteins of 18 strains representative of all
      subgroup A and B genotypes identified in South Africa over a period of 5 years
      were sequenced. F-protein sequences were highly conserved within and between
      South African genotypes, with most variability occurring at the nucleotide level.
      Most of the amino acid differences identified within neutralizing and CTL
      epitopes were conserved within the subtypes, and therefore does not indicate
      immune selection. However, out of three CTL epitopes previously identified in
      subtype A, two (restricted to HLA B*57 and HLA A *01) were conserved only within
      subtype A, while the third (restricted to Cw*12) contained both subtype- and
      genotype-specific changes. These results suggest that most of the identified CTL
      epitopes are subtype A-specific and may not be recognized in subtype B viruses,
      while the HLA Cw*12 restricted epitope may also not be recognized efficiently in
      GA5 strains.

PMID- 15744583
TI  - Testing the possibility to protect bovine PrPC transgenic Swiss mice against
      bovine PrPSc infection by DNA vaccination using recombinant plasmid vectors
      harboring and expressing the complete or partial cDNA sequences of bovine PrPC.
AB  - The objective of this study was to investigate the molecular mechanisms of
      neurobiological processes involved in the degeneration of the central nervous
      system. The bovine spongiform encephalopathy (BSE) was used as experimental model
      system for investigation of transmissible spongiform encephalopathy (TSE). The
      experimental strategy was to evaluate the possibility for protection of bovine
      PrP(C) transgenic mice against a bovine PrP(Sc) infection by DNA vaccination
      using the complete or partial cDNA sequences of the bovine prion protein. Three
      recombinant plasmids pCR3.1-EX-PrP-BSE-C20 (C20), pCR3.1-EX-PrP-BSE-90-235-C4
      (C4), and pCR3.1-EX-PrP-BSE-106-131-C14 (C14) were constructed. These mammalian
      expression vectors harbor complete (C20) or partial (C4 and C14) cDNA sequences
      of the Bos taurus PrP(C) (BTPrP(C)) encoding for amino acid residues 1-264 (C20),
      90-235 (C4), and 106-131 (C14) of the BTPrP(C). Transgenic mice harboring and
      expressing BTPrP(C) were generated using the donor strain C57/CBA, receptor
      strain Swiss mouse, and recombinant plasmid MoPrPXho-boPrP. Crossing of positive
      transgenic mice to bovine PrP and negative to murine PrP with 129/OLA (murine PrP
      /-) and C57BL6x129/OLA (murine PrP+/-) mice was carried out to amplify the colony
      of transgenic mice termed bovine PrP(C) transgenic Swiss mice (BTPrP-TgM). The
      capabilities of C20, C4, and C14 to express the corresponding cDNA sequence of
      BTPrP(C) in vitro and in vivo were confirmed prior to DNA vaccination of the
      BTPrP-TgM using NIH 3T3 cells and BALB/c mice, respectively. In order to prove
      the capability of the constructed expression vectors to protect BTPrP-TgM in vivo
      against a BSE infection 80 female BTPrP-TgM were vaccinated intramuscularly and
      subcutaneously with DNA of the plasmids C20, C4, C14, and parental vector pCR3.1
      (100 microg DNA corresponding to about 26-30 pmol DNA/animal and application) in
      four groups (each consists of 20 animals). DNA vaccination was followed by three
      additional boosters. The vaccinated animals (15 animals of each group) were
      challenged twice per oral with homogenates of brain material obtained from BSE
      cattle containing the infectious PrP(Sc) (100 microl/animal which corresponds to
      15 mg of a 15% brain homogenate). The first and second challenge experiments were
      performed 76-83 and 181 days post DNA vaccination, respectively. A part of the
      vaccinated animals (3-5 animals of each group) that served as internal negative
      control were mock infected using the brain homogenate of healthy cattle or
      Phosphate saline buffer (PBS). A variety of symptoms and clinical pictures were
      observed during the monitoring of DNA vaccinated animals. However, the observed
      diseases seem to be similar in all experimental animal groups. After an
      observation period of 14 months post the second challenge experiment the
      remaining animals (some animals died or were sacrificed when moribund during the
      study) were sacrificed after expiration of the experimental schedule. The right
      hemisphere of the brain and a half of the spleen tissue of the individual animals
      were used for detection of PrP(Sc) by Western blot analysis. The misfolded bovine
      PrP(Sc) was not detected in the brain or spleen tissues of those animals that
      were vaccinated with DNA of C20, which was able to express the complete bovine
      PrP(C) protein in vitro and in vivo. In contrast, the bovine PrP(Sc) was detected
      in the brain or spleen tissues of animals that were DNA vaccinated with DNA of
      the parental vector pCR3.1, with DNA of C4, or with DNA of C14. The results of
      these studies underline that the constructed expression vector C20 possesses the
      protective capacity to inhibit the formation of misfolded bovine PrP(Sc) in BTPrP
      TgM under the conditions used. A delay of occurrence of TSE-specific symptoms in
      the majority of the vaccinated animals seems to be due to the prolonged
      incubation time of BSE infection.

PMID- 15744587
TI  - Pomegranate (Punica granatum) pure chemicals show possible synergistic inhibition
      of human PC-3 prostate cancer cell invasion across Matrigel.
AB  - Four pure chemicals, ellagic acid (E), caffeic acid (C), luteolin (L) and punicic
      acid (P), all important components of the aqueous compartments or oily
      compartment of pomegranate fruit (Punica granatum), and each belonging to
      different representative chemical classes and showing known anticancer
      activities, were tested as potential inhibitors of in vitro invasion of human PC
      3 prostate cancer cells in an assay employing Matrigel artificial membranes. All
      compounds significantly inhibited invasion when employed individually. When C, P,
      and L were equally combined at the same gross dosage (4 microg/ml) as when the
      compounds were tested individually, a supradditive inhibition of invasion was
      observed, measured by the Kruskal-Wallis non-parametric test.

PMID- 15744586
TI  - Resveratrol regulates cellular PKC alpha and delta to inhibit growth and induce
      apoptosis in gastric cancer cells.
AB  - Resveratrol, a dietary phytoalexin, has emerged as a promising chemopreventive
      agent due to its antiproliferative and pro-apoptotic action toward cancer cells
      and its ability to inhibit tumor growth in animals. Gastric adenocarcinoma cells
      respond to resveratrol treatment with suppression of DNA synthesis, activation of
      nitric oxide synthase, induction of apoptosis and inhibition of total PKC and PKC
      alpha activity. Here we demonstrate that treatment of gastric adenocarcinoma SNU
      1 cells with resveratrol results in time and concentration dependent accumulation
      of tumor suppressors p21(cip1/WAF-1) and p53 and is preceded by loss of membrane
      associated PKC delta protein and a concomitant increase in cytosolic PKC alpha.
      Arrest of the cell cycle at transition of S to G(2)/M phases correlates with the
      profile of (3)H-thymidine incorporation and accumulation of p21(cip1/WAF-1) and
      was temporally dependent on increase of p53. SNU-1 cells respond to resveratrol
      treatment with up-regulation of both Fas and Fas-L proteins, whereas in KATO-III
      cells, with deleted p53, only Fas-L is increased after resveratrol treatment.
      Although Fas and Fas-L proteins in SNU-1 cells and Fas-L in KATO-III cells were
      elevated within 24 h of cell treatment with low concentrations of resveratrol,
      significant apoptotic response at these concentrations was observed only after 48
      h. Altogether, our findings indicate that resveratrol engages PKC alpha and delta
      signals in gastric adenocarcinoma SNU-1 cells prior to up-regulation of
      antiproliferative and pro-apoptotic signals. The specific cell death signals
      engaged by resveratrol appear to be cell type dependent and suggest that
      resveratrol has chemopreventive potential even after mutational changes have
      occurred.

PMID- 15744585
TI  - Histone deacetylase inhibitors interact synergistically with tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in carcinoma
      cell lines.
AB  - Both tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and histone
      deacetylase inhibitors (HDIs) show promise for the treatment of cancer. However,
      in a number of reports they have been proven ineffective to induce cell death
      when applied as single agents. In this study, we show that A549 lung carcinoma
      cells and PC-3 prostate carcinoma cells underwent substantial apoptosis when
      coexposed to TRAIL and either suberoylanilide hydroxamic acid, sodium butyrate or
      trichostatin A. HDIs and TRAIL synergized in activation of capase-3, induction of
      internucleosomal DNA fragmentation and promoting mitochondrial damage.
      Significantly, cotreatment with minimally toxic doses of HDIs and TRAIL resulted
      in a marked apoptotic response in both cell lines. These data provide a rationale
      for a more in-depth exploration into the potential of combining TRAIL and HDIs as
      a valuable anticancer strategy.

PMID- 15744589
TI  - Transient respiratory failure possibly associated to imatinib.

PMID- 15744588
TI  - A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in
      patients with advanced or metastatic cancer.
AB  - PURPOSE: VNP40101M is a new alkylating agent that demonstrated broad anti-tumor
      activity in murine tumor models. A phase I trial was initiated to determine the
      toxicities, maximum tolerated dose, and pharmacokinetics of VNP40101M by short IV
      infusion. STUDY DESIGN: The starting dose was 3 mg/m(2) every four weeks, and was
      escalated in successive cohorts as follows: 6, 12, 24, 40, 60, 80, and 100
      mg/m(2). Beyond 100 mg/m(2), dose increments were 25%. Initially, 1-2 patients
      were assigned to a dose level. Intra-patient dose escalation was permitted. With
      the first instance of a drug-related > or = grade 2 adverse event, all dose
      levels required assessment of 3-6 patients. Pharmacokinetic parameters were
      assessed in the first cycle and any cycle with a change in dose. RESULTS: Twenty
      six patients in 13 dose levels ranging from 3-305 mg/m(2) were evaluated. Dose
      related thrombocytopenia was the major toxicity, with the nadir occurring at a
      median of day 27. At 305 mg/m(2), six of eight patients developed grade 3
      thrombocytopenia, including one event that met the definition for DLT. Other dose
      related toxicities included moderate granulocytopenia, anemia, and a mild
      infusion-related syndrome consisting of acute headache and facial flushing. The
      granulocyte nadir occurred at a median of day 34, and recovery of both
      thrombocytopenia and neutropenia to < grade 2 occurred at a median of day 43.
      VNP40101M peak plasma concentrations and AUC were linear with dose. The
      elimination half-life was short and estimated to be approximately 15 minutes.
      CONCLUSIONS: The MTD and recommended dose for phase II trials is 305 mg/m(2)
      every six weeks. Phase II trials in less heavily pre-treated patient populations
      are warranted.

PMID- 15744590
TI  - Prolonged infusion of gemcitabine in advanced solid tumors: a phase-I-study.
AB  - BACKGROUND: Gemcitabine is a pro-drug that has to be phosphorylated to
      gemcitabine-triphosphate in order to exhibit its antineoplastic activity. This
      reaction involves the enzyme deoxycytidine kinase which is saturated at plasma
      concentrations following standard 30-min infusions. Pharmacological studies
      indicate that prolonged administration of gemcitabine might result in higher
      intracellular concentrations of active metabolites. This phase I trial was
      therefore initiated to determine the optimal dose of gemcitabine administered
      over 4 h in patients with advanced solid tumors. PATIENTS AND METHODS: Patients
      were treated with gemcitabine as 4 h-infusion on day 1, 8 and 15 in 4 week
      intervals. The starting dose was 350 mg/m(2). Doses were escalated in 50 mg/m(2)
      increments. RESULTS: Twenty-one patients were treated at doses ranging from 350
      to 450 mg/m(2). The maximum tolerated dose was 400 mg/m(2) with neutropenia,
      thrombocytopenia, stomatitis and elevation of liver enzymes being dose limiting
      toxicities (DLTs). Hematologic and nonhematological toxicities were generally
      mild to moderate. Most common side effects were myelosuppression, nausea,
      elevation of liver enzymes and asthenia. Objective responses were noted in
      patients with hepatocellular carcinoma and cholangio-carcinoma. CONCLUSION: In
      this phase I study of gemcitabine as 4h-infusion, DLTs were neutropenia,
      thrombocytopenia, stomatitis and elevation of liver enzymes. The recommended dose
      for phase II studies is 400 mg/m(2).

PMID- 15744591
TI  - A phase I study of oral ZD 1839 given daily in patients with solid tumors:
      IND.122, a study of the Investigational New Drug Program of the National Cancer
      Institute of Canada Clinical Trials Group.
AB  - PURPOSE: To define the maximum tolerated dose (MTD), the dose limiting toxicity
      (DLT), the biological active (BA) dose and the pharmacokinetics (PK) of the
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa)
      when administered continuously as a once daily dose in patients with advanced,
      incurable solid tumours. PATIENTS AND METHODS: Twenty-eight patients were
      enrolled in cohorts of three from three National Cancer Institute of Canada
      Clinical Trials Group (NCIC CTG) centers. ZD1839 was given at doses from 150 to
      800 mg daily orally and patients underwent a pretreatment and a 28 day post
      treatment tumor biopsy, while PK sampling was performed on days 8, 15, 22, 29,
      and a toxicity assessment every 28 days. RESULTS: All twenty-eight patients were
      evaluable for non-hematological and hematological toxicity. Twenty-seven were
      evaluable for response. The MTD was not reached but DLT included reversible rash
      and diarrhea. One patient with urachal cancer had a transient 55% decrease in
      tumor size and two other patients (breast and non-small cell lung cancer) had
      minor responses; three additional patients had pharmacodynamic evidence of target
      effect. PK demonstrated steady state within the first 2 weeks of dosing and dose
      dependent exposure. CONCLUSION: It appears that ZD 1839 at a dose of 800 m/day
      was tolerable, although some patients required dose modification for diarrhea.
      Doses above 250 m/day demonstrate biologic activity and could be consider for
      future study in a variety of EGFR positive tumor types.

PMID- 15744592
TI  - Impact of taurolidin and octreotide on liver metastasis and lipid peroxidation
      after laparoscopy in chemical induced ductal pancreatic cancer.
AB  - BACKGROUND: There is controversial discussion whether metastasis initiated by
      laparoscopy with carbon dioxide might be prevented by instillation of taurolidin
      or radical scavengers like the somatostatin analogue Octreotide. Therefore we
      evaluated the effects of laparoscopic lavage with taurolidin and Octreotide on
      liver metastasis after staging laparoscopy in ductal pancreatic cancer. METHODS:
      In 60 Syrian hamsters pancreatic adenocarcinoma was induced by weekly subcutanous
      injection of 10 mg N-nitrosobis-2-oxopropylamin/kg body weight for 10 weeks. In
      the 16th week laparoscopic staging biopsy by use of carbon dioxide was performed.
      Finally animals underwent abdominal irrigation with saline (gr.1, n = 20),
      taurolidin (0.5%) (gr.2, n = 20) or Octreotide (gr.3, n = 20). In week 25 animals
      were sacrificed, pancreas and liver were analysed. RESULTS: Size of pancreatic
      carcinomas was decreased in the taurolidin gr. compared to the other two groups.
      Furthermore the number of liver metastasis per animal was reduced after lavage
      with taurolidin (2 +/- 2) and Octreotide (2.5 +/- 2) compared to saline
      irrigation (4 +/- 4) (p < 0.05). Additionally the incidence of port site
      metastases was significantly reduced in the taurolidin group. Activity of
      antioxidative enzyme superoxide dismutase (SOD) was increased while concentration
      of products of lipidperoxidation was decreased in non-metastatic liver after
      taurolidin irrigation compared to saline or Octreotide irrigation. CONCLUSIONS:
      Taurolidin irrigation during laparoscopy might be a new concept to reduce the
      number of liver metastasis and port site metastases in pancreatic cancer.

PMID- 15744593
TI  - A phase II trial of ZD1839 (Iressa) 750 mg per day, an oral epidermal growth
      factor receptor-tyrosine kinase inhibitor, in patients with metastatic colorectal
      cancer.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) appears relevant in the
      pathogenesis and progression of colorectal cancer. After completing a phase I
      pharmacodynamic trial of ZD1839, we undertook a dose expansion trial to examine
      the antitumour efficacy and adverse effect profile of this agent in a homogeneous
      group of patients with metastatic colorectal cancer (CRC). EXPERIMENTAL DESIGN:
      Eligible patients with metastatic or recurrent CRC received ZD1839 750 mg daily
      by mouth. This dose was selected based on a phase I trial conducted by the
      National Cancer Institute of Canada Clinical Trials Group (NCIC CTG). Treatment
      was continued until unacceptable toxicity or disease progression. RESULTS: Twenty
      eight patients were enrolled at three NCIC CTG centers. Twenty-three patients had
      received prior chemotherapy; 12 patients had received three or more regimens. No
      objective responses were observed in 24 evaluable patients, although 8 patients
      had stable disease (median duration of 2.2 months). The most frequent drug
      related adverse events were diarrhea, rash and nausea. Eleven patients required
      dosing modification (hold or reduction), while 3 patients discontinued therapy
      because of toxicity. There were no treatment related deaths. CONCLUSIONS: ZD1839,
      when given at 750 mg/day to patients with pre-treated metastatic colorectal
      cancer, does not result in significant tumor regression.

PMID- 15744594
TI  - Paclitaxel in a novel formulation containing less Cremophor EL as first-line
      therapy for advanced breast cancer: a phase II trial.
AB  - Paclitaxel (Taxol) is formulated in 50% Cremophor EL (CrEL)/absolute ethanol for
      clinical use. In order to reduce vehicle-related side effects, Genetaxyl was
      developed to have paclitaxel formulated in a solution containing lesser amounts
      of CrEL and ethanol plus 2 other solvents. The purpose of the study was to
      evaluate the efficacy and safety of Genetaxyl as first-line therapy to treat
      breast cancer patients. Patients with newly diagnosed stage III (N = 8) or IV (N
      = 10), or recurrent (N = 11) breast cancer received single-agent Genetaxyl at 175
      mg/m(2) administered in a 3-h infusion every 3 weeks for 3-6 cycles. A total of
      148 cycles were delivered to 29 patients. The overall response rate was 41.4%
      (95% confidence interval, 23.4 to 59.2%), and that of patients with metastatic
      disease (N = 20) was 30%. Median survival for all patients was 32.4 months and
      24.3 months for patients having metastatic disease. The toxicity profile seems
      favorable, especially regarding myelosuppression and myalgia/arthralgia. No
      severe hypersensitivity reaction occurred. These phase II trial results
      demonstrate that a 60% reduction of CrEL by Genetaxyl's formulation does not
      affect the activity of paclitaxel and could allow for better control of several
      CrEL-related toxicities.

PMID- 15744595
TI  - Phase II trial of fenretinide in advanced renal carcinoma.
AB  - PURPOSE: Fenretinide, a synthetic form of retinoid, induced apoptosis even in
      chemotherapy resistant cell lines. A phase II study was hence conducted to
      evaluate toxicity and efficacy of fenretinide in metastatic renal cancer.
      METHODS: Eligibility included unresectable or metastatic renal cell carcinoma
      (RCC), adequate organ function and Zubrod performance status < or =2. Prior
      immunotherapy and a maximum of one prior chemotherapy regimen were allowed.
      Fenretinide was administered at a dose of 900 mg/m(2) twice daily orally for 7
      days in a 21-day cycle. Toxicity was assessed at the start of each cycle, and
      response every 2 cycles. RESULTS: Nineteen eligible patients enrolled of which
      fifteen had visceral/bone metastases. Seventeen patients had prior nephrectomy
      and 11 had prior immunotherapy. 76 cycles of therapy were delivered. Therapy was
      very well tolerated with few severe toxicities consisting of thrombosis in 1
      individual and grade 3 fatigue, nausea and diarrhea in 1 patient. 5 patients had
      grade 2 nyctalopia and 3 patients had transient grade 2 visual toxicity. No
      objective responses were noted. Stable disease was seen in seven of nineteen
      cases (37%, 90% C.I. 0.21-0.59). Median time to progression was 1.5 months and
      median duration of stable disease was 5.8 months (90% C.I. 3.0-8.4). Median
      survival was 10 months. Tumor fenretinide levels were obtained in three patients
      and were in the lower end of the therapeutic range. CONCLUSION: Fenretinide was
      well tolerated but demonstrated minimal activity that was consistent with results
      of intratumoral drug measurements. Strategies are needed that will increase
      systemic and tumor levels of fenretinide.

PMID- 15744597
TI  - Hydroxyapatite-coated metals: interfacial reactions during sintering.
AB  - Electrophoretic deposition (EPD) is a low cost flexible process for producing HA
      coatings on metal implants. Its main limitation is that it requires heating the
      coated implant in order to densify the HA. HA typically sinters at a temperature
      below 1150 degrees C, but metal implants are degraded above 1000 degrees C.
      Further, the metal induces the decomposition of the HA coating upon sintering.
      Recent developments have enabled EPD of metathesis-synthesised uncalcined HA
      which sinters at approximately 1000 degrees C. The effects of temperature on HA
      coated Ti, Ti6Al4V, and 316L stainless steel were investigated for dual coatings
      of metathesis HA sintered at 1000 degrees C. The use of dual HA coatings (coat,
      sinter, coat, sinter) enabled decomposition to be confined to the "undercoat" (HA
      layer 1), with the surface coating decomposition free. The tensile strength of
      the three metals was not significantly affected by the high sintering
      temperatures (925 degrees C < T < 1000 degrees C). XRD/SEM/EDS analyses of the
      interfacial zones revealed that 316L had a negligible HA:metal interfacial zone
      (approximately 1 microm) while HA:Ti and HA:Ti6Al4V had large interfacial zones
      (>10 microm) comprising a TiO2 oxidation zone and a CaTiO2 reaction zone.

PMID- 15744596
TI  - Poly(2-hydroxyethyl methacrylate) wound dressing containing ciprofloxacin and its
      drug release studies.
AB  - An improved wound dressing with a long-term drug diffusion-efficacy has been
      developed by UV-radiation technique. It involves incorporation of ciprofloxacin
      (CIP), at the concentration of 0.5-2.0% (w/v), into a water mixture of 2
      hydroxymethacrylate (HEMA) monomer, benzoin isobutyl ether (BIE) initiator and
      different content of ethylene glycol dimethacrylate (EGDMA) cross-linker.
      Increasing the concentration of EGDMA would reduce the releasing ratio of CIP
      from pHEMA. T1/2 is increased from 2.64 to 45.67 h when the EGDMA is added from 1
      to 8%. In the ranges of 0< or = F < or = 0.6, the n value of 1%CIP-pHEMA
      membranes is increased from 0.48 to 0.81. It indicates that the mechanism of drug
      release falls between the Fickian and Case II diffusion model. The antibacterial
      activity of the drug impregnated into the membrane was evaluated by in vitro drug
      kinetic agar plate method. Higher concentration of EGDMA, up to 8% of the cross
      linker, extends the drug release. Comparison with the drug-soaked membranes, the
      newly synthesized 1% CIP-pHEMA membrane (cross-linked with 4% EGDMA) sustains the
      release of the entrapped drug and maintains the antibacterial activity up to 12
      days.

PMID- 15744598
TI  - The influence of passivation and electropolishing on the performance of medical
      grade stainless steels in static and fatigue loading.
AB  - The effects of surface passivation and electropolishing on the mechanical
      performance of a group of biomedical grade stainless steels have been
      investigated. Surface roughness measurements showed that the treatments had a
      significant effect on the final surface finish. However, static mechanical
      testing demonstrated no difference in static mechanical properties, regardless of
      surface treatment. High cycle fatigue testing was carried out at a frequency of
      120 Hz with a load ratio of R=0.1, in both air and a simulated in vivo wet
      corrosive environment. 316LVM (cold worked) proved superior to 316L (annealed) in
      fatigue performance, in both dry and wet environments. The fatigue performance of
      both materials did depend on the surface treatment, with electropolishing
      resulting in better performance than passivation. The fatigue performance of both
      materials was significantly better in the dry environment in comparison to the
      wet environment. The dry-to-wet deterioration in fatigue performance was somewhat
      dependent on the surface treatment for the 316L material but almost independent
      of surface treatment for the 316LVM material. Significant surface pitting and
      damage was evident for 316L during fatigue in the wet environment, whereas almost
      no pitting and damage was observed for 316LVM.

PMID- 15744599
TI  - Comparison between the in vitro surface transformations of AP40 and RKKP
      bioactive glasses.
AB  - Two bioactive silica-phosphate glasses, AP40 and RKKP, were compared in their
      behaviour in simulated biological environment. Their chemical composition is
      practically identical, except that RKKP contains small amounts of amphoteric
      network-former oxides Ta2O5 and La2O3 (composition in wt% for AP40: beta
      Ca3(PO4)2 24.50, SiO2 44.30, CaO 18.60, Na2O 4.60, K2O 0.19, MgO 2.82, CaF2 4.99;
      RKKP: beta-Ca3(PO4)2 24.23, SiO2 43.82, CaO 18.40, Na2O 4.55, K2O 0.19, MgO 2.79,
      CaF2 4.94, Ta2O5 0.99, La2O3 0.09). Previous investigations showed a better
      performance in osteopenic bone for RKKP. To gain more insight into these
      differences in biological behaviour, the in vitro bioactivity of the glasses was
      studied by treatment with a continuously replenished Hanks' Balanced Salt
      Solution (HBSS). The glasses were examined before and after HBSS treatment for 20
      and 40 days by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), X-ray
      Energy Dispersion (EDX), Raman and IR vibrational spectroscopies. Some slight but
      notable differences between the two glasses were observed after HBSS treatment.
      IR and EDX analyses showed that deposits formed on both glasses were composed of
      a calcium deficient carbonate-apatite; however, the layer formed on RKKP glass
      was found to be slightly more calcium deficient and thinner. EDX analysis
      evidenced the presence of a small percentage of F- ions only in the layers formed
      on the RKKP samples. The differences disclosed, although slight, can contribute
      to the understanding of the different biological behaviour previously observed.

PMID- 15744600
TI  - Synthesis and characterization of fluorine-containing hydroxyapatite by a pH
      cycling method.
AB  - Different fluorine-containing hydroxyapatite (FHA) powders were synthesized
      through a pH-cycling method by varying sodium fluoride (NaF) concentration in
      hydroxyapatite (HA) suspensions. The powders were then calcined at 1200 (
      composite function)C for 1 h. Both uncalcined and calcined powders were
      characterized using X-ray diffraction (XRD), Fourier transform infra-red (FTIR),
      and F-electrode. It was discovered that fluorine incorporation increased with the
      fluorine content in the initial solution and the number of pH cycles employed. A
      relatively low fluorine incorporation efficiency, approximately 60%, was attained
      for most of the FHA samples, and it did not vary significantly after calcination.
      It was also revealed that the FHA particles produced by the pH-cycling method
      were inhomogeneous. They were a mixture of hydroxyapatite and F-rich apatite (or
      FA) particles. After calcination, however, these FHA particles were homogenized
      and became single phased FHA.

PMID- 15744601
TI  - Characterization of trypsin immobilized on the functionable alkylthiolate self
      assembled monolayers: a preliminary application for trypsin digestion chip on
      protein identification using matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry.
AB  - Self-assembled monolayers (SAMs) on coinage metal provide versatile modeling
      systems for studies of interfacial electron transfer, biological interactions,
      molecular recognition and other interfacial phenomena. Recently the bonding of
      enzyme to SAMs of alkanethiols onto Au electrode surfaces was exploited to
      produce a bio-sensing system. In this work, the attachment of trypsin to a SAMs
      surface of 11-mercaptoundecanoic acid was achieved using water soluble N-ethyl-N
      '-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide as
      coupling agent. The thickness of SAMs was determined by optical ellipsometer;
      contact angles of the modified Au surfaces were measured in air using a
      goniometer. The Second Harmony Generation data displays the last few percents of
      the alkylthiol molecules adsorbed and produced the complete monolayer by inducing
      the transition from a high number of gauche defects to an all-trans conformation.
      Using X-ray Photoelectron Spectroscopy (XPS) and Fourier-Transformed Infrared
      Reflection-Absorption and Attenuated Total Reflection Spectroscopes (FTIR-RAS and
      ATR), we examined the chemical structures of samples with different treatments.
      By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS), we demonstrated the digestion of bovine serum albumin (BSA) on
      the trypsin-immobilized SAMs surface. Experimental results have revealed that the
      XPS C1s core levels at 286.3 and 286.5 eV (Amine bond), 288.1 eV (Amide bond) and
      289.3 eV (Carboxylic acid) illustrate the immobilization of trypsin. These data
      were also in good agreement with FTIR-ATR spectra for the peaks valued at 1659.4
      cm(-1) (Amide I) and 1546.6 cm(-1) (Amide II). Using MALDI-TOF MS observations,
      analytical results have demonstrated the BSA digestion of the immobilized trypsin
      on the functionalized SAMs surface. For such surfaces, BSA was digested on the
      trypsin-immobilized SAMs surface, which shows the enzyme digestion ability of the
      immobilized trypsin. The terminal groups of the SAMs structure can be further
      functionalized with biomolecules or antibodies to develop surface-base
      diagnostics, biosensors, or biomaterials.

PMID- 15744602
TI  - Biological properties of the intervertebral cages made of titanium containing a
      carbon-carbon composite covered with different polymers.
AB  - Intervertebral cages are used in orthopaedics for stabilization of injured lumbar
      parts of vertebral columns. Our study provides preliminary results of tests of
      the biological properties of titanium cages with a variously modified
      carbon/carbon composite (C/C) core. This core was produced from a C/C composite
      modified by hydrogel materials based on poly(2-hydroxyethyl methacrylate) (HEMA)
      enriched with 1% collagen or 35% methylmethacrylate or 30% terc
      butylmethacrylamide. We evaluated the adhesion of the cells to the tested
      material coating using an in vitro study of the metabolic activity and cytokine
      production of the cells (TNF-alpha, IL-8). We studied the biocompatibility of
      intervertebral cages coated with different copolymers under in vivo condition and
      in an implantation experiment in the porcine femurs. Both in vitro and in vivo
      results revealed favourable biotolerance of the use system. Modification of the
      composite HEMA with the use of collagen seems to have a more positive effect on
      the new bone tissue formed around the implanted devices than HEMA copolymerized
      with methylmethacrylate or terc-butylmethacrylamide.

PMID- 15744603
TI  - DBM induced ectopic bone formation in the rat: the importance of surface area.
AB  - Demineralized bone matrix (DBM) has been shown to induce ectopic endochondral
      bone formation, when intramuscularly implanted in rats. In earlier studies we
      have found a variation in bone formation capacity of this DBM. This might be due
      to the properties of the DBM itself, but the use of DBM blocks could be of
      influence as well. Therefore, this study was designed to investigate whether
      increasing the surface area of the DBM by morsellizing, influences the bone
      formation capacity. In view of this, DBM implants and morsellized DBM (MDBM)
      implants were placed intramuscularly in a rat model. At six weeks the implants
      were retrieved and evaluated by histology and histomorphometry. The results
      demonstrated that significant amounts of newly formed bone were present in some
      DBM as well as some MDBM implants while in others no, or very little new bone was
      found. Histomorphometric analysis showed an average bone formation of 2.6% in DBM
      implants and an average of 1.9% in MDBM implants. Still, the amount of bone
      formation was limited compared with previous studies. It is concluded that
      enlargement of the surface area by morsellizing DBM implants is not an important
      factor in bone forming capacity.

PMID- 15744604
TI  - Dynamic creep and mechanical characteristics of SmartSet GHV bone cement.
AB  - The restrained dynamic creep behaviour and mechanical properties of SmartSet GHV
      bone cement have been investigated at both room temperature and body temperature.
      It was found that the bone cement behaves significant differently at room
      temperature from that at body temperature. The test temperature had a strong
      effect on the creep performance of the bone cements with a higher creep rate
      observed at body temperature at each loading cycle. For both temperatures, two
      stages of creep were identified with a higher creep rate during early cycling
      followed by a steady state creep rate. The relationship between creep deformation
      and loading cycle can be expressed by a Hyperb 1 model. As a visco-elastic
      material, the sensitivity of bone cement to the temperature change was evident
      during mechanical testing. Compared to the mechanical strength at room
      temperature, a decreased value was demonstrated at body temperature. The bending
      modulus was very sensitive to the change in testing temperature, where a
      reduction of 52% was recorded. A significant reduction in compressive and bending
      strength, 31 and 23% were recorded respectively. The effect of temperature on
      bending strength was less apparent, where only 13% reduction was exhibited at
      body temperature compared to room temperature.

PMID- 15744605
TI  - Fabrication of hydroxyapatite ceramics with controlled pore characteristics by
      slip casting.
AB  - Porous hydroxyapatite (HAp) ceramics with controlled pore characteristics were
      fabricated using slip casting method by mixing PMMA with HAp powder. The optimum
      conditions of HAp slip for slip casting was achieved by employing various
      experimental techniques, zeta potential and sedimentation, as a function of pH of
      the slips in the pH range of 4-12. HAp suspensions displayed an absolute maximum
      in zeta potential values and a minimum in sedimentation height at pH 11.5. The
      optimal amount of dispersant for the HAp suspensions was found at 1.0 wt%
      according to the viscosity of 25 vol% HAp slurry. The rheological behaviour of
      HAp slurry displays a shear-thinning behavior without thixotropy, which is needed
      in slip casting processing. The pore characteristics of sintered porous
      hydroxyapatite bioceramics can be controlled by added PMMA particle size and
      volume. The obtained ceramics exhibit higher strength than those obtained by dry
      pressing.

PMID- 15744606
TI  - Formation of apatitic calcium phosphates in a Na-K-phosphate solution of pH 7.4.
AB  - Poorly crystalline, apatitic calcium phosphate powders have been synthesized by
      slowly adding a Na- and K-containing reference phosphate solution with a pH value
      of 7.4 to an aqueous calcium nitrate solution at 37 degrees C. Nano-particulated
      apatitic powders obtained were shown to contain small amounts of Na and K, which
      render them more similar in chemical composition to that of the bone mineral.
      Precipitated and dried powders were found to exhibit self-hardening cement
      properties when kneaded in a mortar with a sodium citrate- and sodium phosphate
      containing starter solution. The same phosphate solution used in powder synthesis
      was found to be able to partially convert natural, white and translucent marble
      pieces of calcite (CaCO3) into calcium-deficient hydroxyapatite upon aging the
      samples in that solution for 3 days at 60 degrees C. Sample characterization was
      performed by using scanning electron microscopy, X-ray diffraction, Fourier
      transform infrared spectroscopy, inductively-coupled plasma atomic emission
      spectroscopy, and simultaneous thermogravimetry and differential thermal
      analysis.

PMID- 15744607
TI  - Electron beam irradiation of denture base materials.
AB  - Electron beam irradiation can be used to influence the properties of polymers. It
      was the aim of this study to investigate whether PMMA denture base materials can
      benefit from irradiation in order to have increased fracture toughness, work of
      fracture or hardness. Rectangular specimens of heat-and auto-curing denture base
      materials were electron beam irradiated (post-cured) with 25, 100 and 200 kGy
      using an electron acceleration of 10 MeV or 4.5 MeV respectively. Fracture
      toughness, work of fracture, Vickers hardness and colour changes were measured
      and compared with not-irradiated specimens. The toughness, work of fracture and
      hardness increased using 10 MeV with a dose of 25 kGy and with 100 kGy using 4.5
      MeV. However, the clinical use may not benefit from the observed small changes.
      Higher dosage (200 kGy) decreased the values significantly. The colour changes
      reached a level which was found to be not clinically acceptable. CONCLUSION: PMMA
      denture base materials do not benefit from post-curing with electron beam
      irradiation.

PMID- 15744608
TI  - Measurement of mechanical properties of rectal wall.
AB  - In this paper, a pig's rectum was studied as a model biomaterial and its
      mechanical behaviors under tensile, compressive, and shear stresses were measured
      accurately using a multipurpose microtesting system. Based on the stress-strain
      relations of samples of different orientations, the tangential moduli were
      calculated through a reverse method combined with self-correlation analysis. The
      experimental data exhibited pronounced nonlinear and anisotropic characteristics.
      It was found that the effective compliance in tension along the longitudinal
      direction was larger than that along the circumferential direction, but smaller
      than that along the out-of-plane direction.

PMID- 15744609
TI  - Hydroxyapatite porous scaffold engineered with biological polymer hybrid coating
      for antibiotic Vancomycin release.
AB  - The purpose of this study is to improve hydroxyapatite (HA) porous scaffolds via
      coating with biological polymer-HA hybrids for use as wound healing and tissue
      regeneration. Highly porous HA scaffolds, fabricated by a polyurethane foam
      reticulate method, were coated with hybrid coating solution, consisting of
      poly(epsilon-caprolactone) (PCL), HA powders, and the antibiotic Vancomycin. The
      PCL to HA ratio was fixed at 1.5 and the drug amounts were varied [drug/(PCL +
      HA) = 0.02 and 0.04]. For the purpose of comparison, bare HA scaffold without the
      hybrid coating layer was also loaded with Vancomycin via an immersion-adsorption
      method. The hybrid coating structure and morphology were observed with Fourier
      transformed infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM).
      The effects of the hybrid coating on the compressive mechanical properties and
      the in vitro drug release of the scaffolds were investigated in comparison with
      bare HA scaffold. The PCL-HA hybrid coating altered the scaffold pore structure
      slightly, resulting in thicker stems and reduced porosity. With the hybrid
      coating, the HA scaffold responded to an applied compressive stress more
      effectively without showing a brittle failure. This was attributed to the
      shielding and covering of the framework surface by the coating layer. The
      encapsulated drugs within the coated scaffold was released in a highly sustained
      manner as compared to the rapid release of drugs directly adsorbed on the pure HA
      scaffold. These findings suggest that the coated HA scaffolds expand their
      applicability in hard tissue regeneration and wound healing substitutes
      delivering bioactive molecules.

PMID- 15744610
TI  - Corrosion testing of sintered samples made of the Co-Cr-Mo alloy for surgical
      applications.
AB  - Corrosion resistance of high quality sintered compacts made of the Co-Cr-Mo alloy
      powder in manufacturing bone implants has been investigated. The samples met the
      characteristic mechanical requirements for this kind of implants, but the
      increased density of the porous material turned out to be crucial in the
      improvement of their corrosion resistance. It seems that the rotary cold
      repressing (RCR) of sintered compacts could be a very advantageous alternative to
      the single or multiple matrix pressing. The influence of cold repressing and the
      subsequent heat treatment of sintered compacts made of the Co-Cr-Mo powder on the
      changes of their density, microstructure, and corrosion resistance was
      investigated in this work.

PMID- 15744611
TI  - New chemical treatment for bioactive titanium alloy with high corrosion
      resistance.
AB  - It was recently claimed that titanium metal and its alloys can bond to the living
      bone, without being coated by apatite (VPS coatings), but by being chemically and
      heat-treated. The bioactivity of treated titanium is of interest because of the
      opportunity to obtain orthopaedic or dental implants presenting, at the same
      time, high toughness, strength and fatigue resistance as well as bone-bonding
      ability. The bioactive behaviour of the treated implants is due to the presence
      of a modified surface, which, during soaking in body fluid, promotes the
      precipitation of apatite. The apatite formed is strongly bonded to the substrate
      and promotes living bone bonding. In this work were characterised samples of Ti
      6Al-7Nb alloy with surfaces presenting a different chemical and mechanical state.
      The aim of the research was twofold. The first objective was to characterise
      chemically and heat-treated samples with different surface topography, in order
      to define the best conditions for osteogenic integration. The second aim was to
      assess the corrosion behaviour of the bioactive implants, because they expose a
      microporous and quite thin modified surface layer. No-treated and passivated
      samples, with a surface state closed to that nowadays used on implants, were used
      as reference. The surface structure, morphology, electrochemical behaviour and
      bioactivity of the different samples were assessed by means of XRD, SEM-EDS,
      anodic polarizations, open circuit measurements and in-vitro tests. Results
      evidence that it is possible to modify the surface of the Ti-6Al-7Nb alloy in
      order to obtain the formation of a bioactive layer and that the substrate
      roughness influences the characteristics of the surface layer formed. It was also
      evidenced that the as treated surfaces present inadequate corrosion behaviour, so
      a new two-step chemical treatment has been developed in order to obtain a
      bioactive material with good corrosion resistance.

PMID- 15744612
TI  - Preparation and in vitro investigation of chitosan/nano-hydroxyapatite composite
      used as bone substitute materials.
AB  - Chitosan/nano-hydroxyapatite composites with different weight ratios were
      prepared through a co-precipitation method using Ca(OH)(2), H(3)PO(4) and
      chitosan as starting materials. The properties of these composites were
      characterized by means of TEM, IR, XRD, burn-out test and universal matertial
      test machine. Additionally, in vitro tests were also conducted to investigate the
      biodegradability and bioactivity of the composite. The results showed that the HA
      synthesized here was poorly crystalline carbonated nanometer crystals and
      dispersed uniformly in chitosan phase and there is no phase-separation between
      the two phases. Because of the interactions between chitosan and n-HA, the
      mechanical properties of these composites were improved, and the maximum value of
      the compressive strength was measured about 120 MPa corresponding to the
      chitosan/n-HA composite with a weight ratio of 30/70. The specimens made of 30/70
      chitosan/n-HA composite exhibit high biodegradability and bioactivity when being
      immersed in SBF solutions. The composite is appropriate to being used as scaffold
      materials for bone tissue engineering. (c) Springer Science + Business Media,
      Inc.

PMID- 15744614
TI  - Laser bonded microjoints between titanium and polyimide for applications in
      medical implants.
AB  - Bioencapsulation of medical implant devices, and neural implant devices in
      particular, requires development of reliable hermetic joints between packaging
      materials that are often dissimilar. Titanium-polyimide is one of the
      biocompatible material systems, which are of interest to our research groups at
      Wayne State University and Fraunhofer USA. We have found processing conditions
      for successful joining of titanium with polyimide using near-infrared diode
      lasers or fiber lasers along transmission bonding lines with widths ranging from
      200 to 300 microm. Laser powers of 2.2 and 3.8 W were used to create these
      joints. Laser-joined samples were tested in a microtester under tensile loading
      to determine joint strengths. In addition, finite element analysis (FEA) was
      conducted to understand the stress distribution within the bond area under
      tensile loading. The FEA model provides a full-field stress distribution in and
      around the joint that cause eventual failure. Results from the investigation
      provide an initial approach to characterize laser-fabricated microjoints between
      dissimilar materials that can be potentially used in optimization of bio
      encapsulation design.

PMID- 15744613
TI  - Short-term in vitro and in vivo biocompatibility of a biodegradable polyurethane
      foam based on 1,4-butanediisocyanate.
AB  - In this study short-term in vitro and in vivo biocompatibility apects of a
      biodegradable polyurethane (PU) foam were evaluated. The PU consists of hard
      urethane segments and amorphous soft segments based on a copolyester of dl
      lactide and epsilon-caprolactone. The urethane segments are of uniform length and
      synthesized with 1,4-butanediisocyanate. The foam has good mechanical properties
      and will be used for tissue regeneration applications. Degradation tests were
      carried out in a buffer solution for twelve weeks. Cytotoxicity was determined
      using extract and direct contact test methods with incubation periods varying
      form 24 to 72 h. The foam was implanted subcutaneously for one, four and twelve
      weeks and the tissue response to the material was histologically evaluated. In
      vitro, the mass loss was 3.4% after twelve weeks. In the cytotoxicity tests the
      PU caused no abnormal growth behaviour, nor morphological changes or inhibition
      in metabolic activity. The in vivo studies showed no toxic tissue response to the
      PU. Connective tissue ingrowth, accompanied by vascular ingrowth was complete at
      twelve weeks. In vivo degradation had started within four to twelve weeks. In
      conclusion, the PU shows a good in vitro and in vivo biocompatibility in these
      short-term experiments.

PMID- 15744615
TI  - Determination of diffusion coefficients of glycerol and glucose from starch based
      thermoplastic compounds on simulated physiological solution.
AB  - Blends of corn starch with poly(ethylene-vinylalcohol) copolymer (SEVA-C) have
      been studied and reported as biodegradable. These materials are known to be
      sensitive to enzymatic action, evidencing a degradation of the starch phase in
      alpha-amylase assays. However, from the physical-chemical point of view the
      degradation of the blend is mainly associated with the leaching of glycerol,
      since other compounds are not released and no carbohydrates were found in the
      degradation solution. Based on these results, the present work attempts to
      determinate the respective diffusion coefficients. Four different experiments
      were performed, using samples with different thicknesses that were immersed in a
      simulated physiological solution. High performance liquid chromatography (HPLC)
      was used to separate the sugar derivatives and glycerol from the degradation
      solutions. The obtained data were fitted to an empirical model to allow the
      estimation of the diffusion coefficient for glycerol and glucose, based on the
      analytical solution for Fick's law of diffusion, and a good agreement was found
      (R(2) equals approximately 1). The glycerol leaches quickly out during the first
      few days of immersion, stabilizing thereafter, presenting greater diffusion
      coefficients for thicker samples. As the quantity of saccharides in the solution
      remains almost invariable along the experiments, this work also confirms that the
      degradation process is difficult without the action of enzymes.

PMID- 15744616
TI  - Cytocompatibility of novel tin oxide thin films.
AB  - The capacity of tin oxide films to support cell growth was investigated. Three
      substrates were used for the test: glass coverslips, glass coverslips spin coated
      with tin oxide and commercially available 316 stainless steel. The wettabilities
      and surface roughness of the three surfaces were measured before seeding 3T3
      fibroblasts onto the samples. The behaviour of the cells grown on the tin oxide
      was compared to the uncoated glass and the steel and results showed that the cell
      growth on tin oxide compared favourably with the other substrates. The surface
      wettability appeared to have the strongest effect on cell adhesion to tin oxide.

PMID- 15744618
TI  - Sol-gel processing of drug delivery materials and release kinetics.
AB  - Silica, calcium (5 mol%) silicate and silica/polycaprolactone hybrid
      inorganic/organic amorphous materials, all mixed with sodium ampicillin, a broad
      spectrum antibiotic, have been synthesized by sol-gel method. The amorphous
      nature of the gels was ascertained by X-ray diffraction analysis. Release
      kinetics in a simulate body fluid (SBF) have been subsequently investigated. The
      amount of sodium ampicillin released has been detected by UV-Vis spectroscopy and
      SEM. The release kinetics seems to occur in more than one stage. Finally FTIR
      measurements and SEM micrograph showed the formation of a hydroxyapatite layer on
      the surface of the samples soaked in SBF. All data showed that these materials
      could be used as drug delivery bioactive systems.

PMID- 15744617
TI  - Bonelike/PLGA hybrid materials for bone regeneration: preparation route and
      physicochemical characterisation.
AB  - Bonelike/PLGA hybrid materials have been developed using gamma-MPS as silane
      coupling agent between the inorganic and organic phases for controlled drug
      delivery applications. Silanization showed to be more effective when cyclohexane
      was used as a non-polar solvent (nP method) due to a chemical interaction between
      Bonelike, and the silane film, while by using a 95/5 (V/V) methanol/water as a
      polar solvent (P method), a much thinner film was achieved. Functional groups of
      PLGA, such as the carbonyl group (C=O), were identified using Raman and FTIR-ATR
      analysis and therefore these groups may be used to link therapeutic molecules.
      These novel hybrid materials prepared by combining silanization and post
      hybridisation processes are expected to find use in medical applications of bone
      regeneration and as drug delivery carrier for therapeutic molecules.

PMID- 15744619
TI  - Biological response to pre-mineralized starch based scaffolds for bone tissue
      engineering.
AB  - It is known that calcium-phosphate (Ca-P) coatings are able not only to improve
      the bone bonding behaviour of polymeric materials, but at the same time play a
      positive role on enhancing cell adhesion and inducing the differentiation of
      osteoprogenitor cells. Recently an innovative biomimetic methodology, in which a
      sodium silicate gel was used as a nucleative agent, was proposed as an
      alternative to the currently available biomimetic coating methodologies. This
      methodology is especially adequate for coating biodegradable porous scaffolds. In
      the present work we evaluated the influence of the referred to treatment on the
      mechanical properties of 50/50 (wt%) blend of corn starch/ethylene-vinyl alcohol
      (SEVA-C) based scaffolds. These Ca-P coated scaffolds presented a compressive
      modulus of 224.6 +/- 20.6 and a compressive strength of 24.2 +/- 2.20.
      Cytotoxicity evaluation was performed according ISO/EN 10993 part 5 guidelines
      and showed that the biomimetic treatment did not have any deleterious effect on
      L929 cells and did not inhibit cell growth. Direct contact assays were done by
      using a cell line of human osteoblast like cells (SaOS-2). 3 x 10(5) cells were
      seeded per scaffold and allowed to grow for two weeks at 37( composite function)C
      in a humidified atmosphere containing 5% CO(2). Total protein quantification and
      scanning electron microscopy (SEM) observation showed that cells were able to
      grow in the pre-mineralized scaffolds. Furthermore cell viability assays (MTS
      test) also show that cells remain viable after two weeks in culture. Finally,
      protein expression studies showed that after two weeks osteopontin and collagen
      type I were being expressed by SaOS-2 cells seeded on the pre-mineralized
      scaffolds. Moreover, alkaline phosphatase (ALP) activity was higher in the
      supernatants collected from the pre-mineralized samples, when compared to the
      control samples (non Ca-P coated). This may indicate that a faster mineralization
      of the ECM produced on the pre-mineralized samples was occurring. Consequently,
      biomimetic pre-mineralization of starch based scaffolds can be a useful route for
      applying these materials on bone tissue engineering.

PMID- 15744620
TI  - The effect of formation of the liquid crystalline phase on the blood
      compatibility of a cholesterol modified silicone.
AB  - Cholesterol modified silicones were synthesized by grafting copolymerization of
      10-Cholesteryloxydecanol onto polymethylhydrosiloxane (PMHS). Fourier transform
      infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance ((1)H-NMR)
      spectroscopy and gel permeation chromatography (GPC) confirmed the chemical
      structures of polymers. Differential scanning calorimetry (DSC) and polarized
      optical microscopy (POM) results indicated the mesogenic properties of those
      polymers. The modified silicone with 45% 10-Cholesteryloxydecanyl (SC45)
      indicated obvious thermotropic liquid crystalline transform at about 122-124.9
      degrees C. The thermotropic liquid crystalline phase could be retained at room
      temperature via a special annealing/quenching process. The anneal-quenched film
      (SC45C) formed continuous liquid crystalline phase, whereas the unannealed films
      presented amorphous structure. The blood compatibility of the coatings was
      assessed from SEM observation of the platelet's adhesion to coating surface and
      plasma recalcification time (PRT). The results revealed that the formation of the
      liquid crystalline phase could greatly improve the in vitro blood compatibility
      of the materials. The positive results of liquid crystalline onto
      haemocompatibility allow broad potential in biomaterials.

PMID- 15744621
TI  - Technique and image quality of intraoperative indocyanine green angiography
      during aneurysm surgery using surgical microscope integrated near-infrared video
      technology.
AB  - OBJECTIVE: To describe the technical integration of indocyanine green (ICG) near
      infrared technology into the optical path of the surgical microscope and to
      report on the image quality achieved by this method. We hypothesized that ICG
      angiography permits a simple and quick intraoperative assessment of vessel
      patency and aneurysm occlusion after clip placement. METHODS: A special
      arrangement of filters was designed to allow the passage of near-infrared light
      required for the excitation of ICG fluorescence (700-850 nm) from a modified
      microscope light source into the surgical field and the passage of ICG
      fluorescence (780-950 nm) from the surgical field back into the optical path of
      the surgical microscope (Carl Zeiss, Oberkochen, Germany). Thus, ICG angiography
      could be completely performed with a surgical microscope. 20 patients with
      intracranial aneurysms were included in the technical evaluation of the new
      method. RESULTS: Image quality and spatial resolution were excellent and
      permitted a real-time assessment of vessel patency and aneurysm occlusion if the
      structures of interest were visible to the surgeon's eye under the microscope,
      including perforating arteries with a diameter of less than 1 millimeter. In 1
      patient, vessel occlusion by the clip was found and in 1 case residual filling of
      the aneurysm was diagnosed. Both cases could be treated by clip correction within
      2 minutes after primary placement of the clip. In all cases, the intraoperative
      findings correlated with the postoperative digital subtraction angiography.
      CONCLUSIONS: ICG angiography using a surgical microscope is valuable for the
      intraoperative imaging of arterial and venous flow in all visible vessels
      including small perforating arteries. The simplicity of the method and the speed
      with which the investigation can be performed indicate that this technique may
      help to improve the quality and outcome of surgical procedures and reduce the
      need for intra- or postoperative angiography in selected cases.

PMID- 15744623
TI  - Endovascularly or surgically treated vertebral artery and posterior inferior
      cerebellar artery aneurysms: clinical analysis and results.
AB  - OBJECTIVE: To describe the clinical results in patients with aneurysms of the
      vertebral artery and posterior inferior cerebellar artery complex (VA-PICA)
      treated by endovascular embolization or surgically in cases considered
      untreatable by endovascular methods. PATIENTS AND METHODS: During a 5-year-period
      a total of 28 patients with a VA-PICA complex aneurysm out of 600 patients
      received definitive treatment, 19 patients by endovascular embolization and 9
      patients surgically. Mean age was 54 years (range 9-75 years). Clinical data,
      intraoperative observations and procedural complications were evaluated. The mean
      follow-up was 9 months. RESULTS: Hunt-Hess (HH) grades were HH 0-II in 10
      patients (35.7 %), HH III in 6 patients (21.4 %) and HH IV + V in 12 patients
      (42.9 %). Aneurysm size ranged from 2 to 40 mm (mean size 5.5 mm). Aneurysm
      configuration was saccular 18, fusiform 7 and multilobed 3. Complete occlusion
      was achieved in all cases. Overall 67.9 % (n = 19) showed a favorable outcome
      (Glasgow Outcome Score IV + V). Overall procedure-related rate for permanent
      morbidity and mortality was 3.6 % (n = 1) and 3.6 % (n = 1), respectively.
      Predictive factors of clinical outcome were the initial clinical HH grade and the
      Fisher grade. CONCLUSION: Endovascular embolization is an effective method for
      the treatment of VA-PICA aneurysms. Surgical clipping is still an alternative and
      should be considered for "uncoilable" lesions. Outcomes showed a close
      correlation to the initial clinical state and were not dependent on the treatment
      modality.

PMID- 15744624
TI  - Volumetric analysis of the growth rate of incompletely resected intracranial
      meningiomas.
AB  - OBJECTIVE: Intracranial meningiomas are mostly considered to be slow growing
      tumors. However, only a few previous reports provide information on the growth
      rate of these tumors. The aim of this study was to determine the growth rates of
      intracranial meningiomas after subtotal resection, analysing their relation to
      radiological appearance and histological features. Results are compared with our
      previous analysis of growth rates in incidental meningiomas . METHODS: The
      hospital charts, follow up records and imaging studies were reviewed in 36
      patients with subtotally resected intracranial meningiomas. The tumor growth
      rates were determined by calculating the absolute and relative growth rates and
      the tumor volume doubling times. RESULTS: In the group of 33 patients with
      histologically verified grade 1 meningiomas, the mean absolute growth rate was
      1.51 cm (3)/year, the median relative growth rate and tumor doubling time was
      14.18 %/year and 5.228 years. In young patients annual relative growth rates were
      significantly higher. The median annual relative growth rate of meningiomas with
      calcification was significantly lower than in tumors without calcification. Also
      tumors with hypo- or isointense T (2)-signals on MRI revealed a lower growth
      rate. There was no significant difference between males and females. Histological
      studies revealed 22 meningiomas of a meningotheliomatous subtype, 8 fibrous and 3
      psammomatous meningiomas. The comparison of growth rates between these subtypes
      did not show any significant differences. In atypical meningiomas (WHO grade 2),
      absolute and relative growth rates were significantly higher and tumor doubling
      times shorter. CONCLUSION: The majority of intracranial meningiomas are slow
      growing tumors, although the growth rates may vary widely even among benign grade
      1 meningiomas. In meningiomas after subtotal surgical resection, the age of the
      patients seems to present a predictive factor for tumor growth in analogy to our
      previous observation in incidental meningiomas. Significantly higher relative
      growth rates were detected in younger patients. Gender does not seem to play a
      major role as a predictive factor. Radiological features such as calcification or
      T (2)-signal intensity may provide additional information to predict the growth
      potential of meningiomas. Close clinical and radiological observation should be
      performed in young patients harboring tumors with absence of calcification or
      high T (2)-signal intensities due to the higher growth potential in this patient
      group.

PMID- 15744625
TI  - Experience with five different intervertebral disc spacers for cervical
      spondylodesis.
AB  - The ventral spondylodesis with autologeous bone graft for degenerative disease of
      the cervical spine bears the disadvantage of complications and heavy pain at the
      superior pelvic straight. To reduce these problems the intervertebral disc spacer
      was developed. Between September 1997 and January 2002 we operated on 207
      patients suffering from degenerative disease -- osteochondrosis and/or disc
      prolapse -- of the cervical spine. Without any patient selection, e. g. according
      to a randomized sample, we implanted the different disc spacer by a ventral
      approach after microsurgical discectomy and removal of the dorsal osteophytes by
      a high-speed drill. The Titanium disc spacer by Aesculap, Weber, Intromed, and
      Medinorm were used in 66, 54, 52 and 18 cases and the Carbonium disc spacer of
      AcroMed in 17 cases. We evaluated the handling, X-ray contrast, costs of
      implantation and the clinical results after 3 months and 1 year. All the five
      disc spacers are suitable for the ventral spondylodesis of the cervical spine.
      The titanium spacer from Weber is characterized by its comfortable handling and a
      price in the mean range. A good cost effectiveness and an easy handling is given
      by the Intromed-cage. The X-ray contrast of the Carbonium spacer by AcroMed is
      insufficient in the lower cervical spine. The handling is good, but the price is
      too high. The AcroMed, Medinorm and Intromed spacer have the tendency to migrate
      into the vertebral endplates. A final statement can only be given after the
      achievement of long-term results.

PMID- 15744627
TI  - Metastatic meningioma WHO grade II of the cervical spine: case report and review
      of the literature.
AB  - The authors report a rare case of metastatic atypical meningioma WHO grade II
      involving the dorso-lateral region of the cervical spine and causing spinal cord
      compression in a 76-year-old man. The patient was treated surgically in June 1998
      for an atypical parasagittal meningioma in the right frontal lobe. Local
      recurrence with extension to the left hemisphere required surgical treatment in
      January 2000, and in December 2000 recurrence caused paraplegia of the lower
      extremities and paresis of the left arm. A 3 (rd) operation was carried out in
      January 2001, followed by radiotherapy with a total dose of 45 Gy. The patient
      presented again in March 2003 because of pain in the neck and a progredient new
      paresis and paresthesia of the right arm. Computed tomogram of the cervical spine
      showed a large tumor with compression of the spinal cord. MRI was not possible
      due to a pacemaker which had been implanted in the meantime. Surgical subtotal
      removal of the tumor via hemilaminectomy of the 3 (rd) and 4 (th) cervical
      vertebrae was performed. After decompression of the cervical spine the paresis of
      the right arm improved, the paraplegia of the legs and the left arm, existing
      since December 2000, remained unchanged. Histological findings of the cranial
      lesions and the metastatic lesion had a similar appearance and were compatible
      with atypical meningioma (WHO grade II).

PMID- 15744628
TI  - High-dose radiation-induced meningioma in children - case report and critical
      review of the literature.
AB  - OBJECT: High-dose radiation-induced meningiomas in children are a rare
      occurrence. We discuss the clinical data and the differences of these rare tumors
      from those of spontaneous counterpart and radiation-induced meningiomas of the
      adult population. CASE REPORT: We report a case of meningothelial meningioma,
      which occurred in a 9-year-old boy who underwent radiotherapy for a parieto
      occipital cutaneous angioma. In addition, we collected 18 cases of high-dose
      radiation-induced meningiomas in children from a literature review with Medline.
      RESULTS: Radiation-induced meningiomas in children show a female predominance, a
      short latency period that seems to be related to the age at irradiation, and an
      aggressive behaviour. CONCLUSION: Exposure to the potentially carcinogenic
      effects of radiotherapy should be reserved only for tumors that demonstrate
      subsequent progression. A meticulous follow-up of patients treated with radiation
      therapy is mandatory.

PMID- 15744629
TI  - Spinal extradural arachnoid cyst causing cord compression in a 15-year-old girl:
      a case report.
AB  - The authors describe the case of a fifteen-year-old girl with progressive
      paraparesis of the lower limbs that was caused by an intraspinal extradural
      dorsal arachnoid cyst at the level of Th 3-6. Diagnosis was established with MRI
      and MRI myelography. The latter revealed the CSF-like content of the cyst. The
      patient underwent laminotomy and en bloc resection of the cyst. Ligation of the
      pedicle of the cyst was done with laminoplasty. Quick and complete recovery was
      observed after surgery.

PMID- 15744630
TI  - Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and
      newer antidepressants: a meta-analysis of clinical trial data.
AB  - BACKGROUND: In the last ten years, SSRIs have increasingly replaced TCAs as
      comparators of newer antidepressants (ADs), because of their better tolerability
      profile. In particular, fluoxetine has become a reference drug for the treatment
      of depression, but the occurrence of individual side effects in depressed
      subjects treated with fluoxetine and each comparator AD have not been
      systematically investigated. METHODS: This meta-analysis investigated the
      frequency of side effects induced by fluoxetine or alternative ADs and compared
      the occurrence of individual side effects in depressed subjects. All randomised
      clinical trials (RCTs) comparing fluoxetine with any other AD drug in patients
      with major depression were located by searching the Cochrane Collaboration
      Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane
      Controlled Trials Register. Two reviewers independently extracted information.
      RESULTS: Significantly less percentage of patients treated with fluoxetine
      experienced any side effects in comparison with TCAs (50.9 % vs 60.3 %, 29 RCTs;
      RR = 0.84, p = 0.003), but not in comparison with other SSRIs (59.4 % vs 59.3 %,
      15 RCTs; RR = 1.00, p = 0.902). In addition, fluoxetine was better tolerated in
      comparison with TCAs and related ADs (RR 0.61, 95 % CI 0.52, 0.71), but not in
      comparison with other SSRIs. Regard to individual side effects, activating
      (insomnia, agitation, tremor and anxiety) and gastrointestinal adverse events
      (nausea, vomiting, diarrhoea, weight loss and anorexia) were significantly more
      frequent in fluoxetine-treated patients, whereas cholinergic side effects were
      significantly less frequent. CONCLUSIONS: Fluoxetine compared to other ADs had
      more activating and gastrointestinal adverse effects, which often require
      additional pharmacotherapy or other managements strategies, leading to
      discontinuation and non-compliance and increasing the costs. This information is
      relevant to base on evidence the prescription of ADs in everyday clinical
      practice.

PMID- 15744631
TI  - Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a
      once-daily dosage in comparison with sertraline.
AB  - OBJECTIVE: The objective of this double-blind, multi-center clinical study was to
      demonstrate the non-inferiority of hypericum extract versus sertraline in the
      treatment of moderate depression. METHODS: A total of 241 patients with a
      diagnosis of moderate depressive disorder (according to ICD-10 criteria) were
      randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum
      group n = 123; sertraline group n = 118). According to the study protocol, 200
      patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98
      sertraline); 81 patients in the hypericum group and 80 in the sertraline group
      were treated after week 12 for an additional 12 weeks. Thus, most patients were
      treated for a period of 6 months. The primary efficacy variable was the 17-item
      HAMD total score at the end of the first 12-week double-blind treatment period.
      RESULTS: After the first 12-week treatment period, the HAMD score decreased from
      almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1
      points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points
      (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population.
      The statistical test for non-inferiority (boundary delta = 3) revealed that
      hypericum extract is not inferior to sertraline ( P < 0.0001). The mean
      difference between the treatments was 0.1995 points, with a corresponding one
      sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued
      treatment in the follow-up phase, the HAMD score at the end of the study was 5.7
      +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group).
      Comparable improvement was also found for the von Zerssen's Adjective Mood Scale
      (BfS) and CGI during the first and second 12-week treatment period in both
      treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in
      the sertraline group, the percentage of patients rated as responders did not
      differ significantly between treatment groups (12 weeks). The adverse events of
      12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline
      group (13.6 %) were possibly related to study medication. No basic differences in
      the treatment groups were observed and no interaction with concomitant medication
      was documented. In most cases , the investigators assessed the tolerability of
      hypericum extract and sertraline as "good" or "very good." CONCLUSIONS: The
      results indicate that hypericum extract STW 3 is not inferior to sertraline and
      that it is a well-tolerated drug for the treatment of moderate depression. These
      favorable effects were achieved with a once-daily dose of 612 mg of hypericum
      extract given for up to 24 weeks.

PMID- 15744633
TI  - Increased serum nitrite/nitrate (NOx) and malondialdehyde (MDA) levels during
      alcohol withdrawal in alcoholic patients.
AB  - Serum nitrite/nitrate (NOx) and malondialdehyde (MDA) levels of 40 male alcoholic
      patients and 14 healthy male controls were investigated. Severity of alcohol
      withdrawal in alcoholic patients was evaluated by using the Clinical Institute
      Withdrawal Assessment for Alcohol (CIWA-Ar) scale just before taking the blood
      samples. NOx levels in serum samples were determined based on the reduction of
      nitrate to nitrite by vanadium chloride. MDA levels were also determined
      spectrophotometrically at 540 nm. The total CIWA-Ar score of alcohol-withdrawn
      patients was found to be 17.7. NOx and MDA levels were significantly increased in
      alcoholics during alcohol withdrawal as compared to control subjects. In
      conclusion, we observed increased serum NOx levels and lipid peroxidation during
      alcohol withdrawal in alcoholic patients.

PMID- 15744632
TI  - Impact of experimentally induced serotonin deficiency by tryptophan depletion on
      saliva cortisol concentrations.
AB  - BACKGROUND: Tryptophan depletion (TD) has been shown to induce a transient mood
      lowering effect in psychiatric patients and susceptible healthy subjects. We
      investigated the effects of TD on cortisol secretion in psychiatric patients and
      healthy subjects based on the hypothesis that the potential mood-lowering effects
      may be associated with increased activity of the hypothalamic-pituitary-adrenal
      axis, thus leading to a rise of cortisol secretion. METHODS: After TD at 18.00 h,
      salivary cortisol was sampled in the evening and on the following morning. The
      first study was a randomized, placebo-controlled, crossover study in healthy
      subjects. Two further open trials in patients with obsessive-compulsive disorder
      (OCD) and primary insomnia compared the effects of TD on cortisol with baseline
      conditions. RESULTS: In healthy subjects, TD significantly diminished cortisol
      the next morning compared with placebo. In OCD patients and primary insomniacs,
      cortisol the morning after TD was lowered compared with baseline. Evening
      cortisol was not affected by TD in any of the groups. CONCLUSIONS: Contrary to
      expectation, TD led to a comparable decrease of morning cortisol in all groups
      investigated. However, these findings are consistent with former studies
      analyzing the impact of antiserotonergic drugs on cortisol secretion. The results
      underline that the antiserotonergic effects caused by TD may influence cortisol
      secretion.

PMID- 15744634
TI  - Treatment of alcohol withdrawal syndrome with combined carbamazepine and tiapride
      in a patient with probable sleep apnoe syndrome.
AB  - The most frequently used agents for treatment of alcohol withdrawal syndrome are
      benzodiazepines and clomethiazole. Both have the main disadvantage of potential
      misuse and respiratory depression. Therefore their use in patients with
      respiratory diseases is limited. In recent years a treatment strategy with
      combined carbamazepine and tiapride was reported to be an effective alternative
      in alcohol withdrawal without the risk of respiratory depression. We report the
      successful treatment with carbamazepine and tiapride of a patient with probable
      sleep apnoe syndrome and history of withdrawal-related epileptic seizures.

PMID- 15744635
TI  - Little effects of low dosage of levomepromazine on plasma risperidone levels.
AB  - In the present study, we investigated the effects of levomepromazine on plasma
      risperidone concentrations in a steady state. Twenty patients taking risperidone
      at a stable dose for more than 2 weeks who were considered to require
      levomepromazine coadministration were selected. The scores of excitement in BPRS
      significantly decreased 2 weeks after the coadministration of levomepromazine.
      Plasma risperidone concentrations and the ratio of risperidone and 9
      hydroxyrisperidone (risperidone/9-hydroxyrisperidone) did not change between
      before and 2 weeks after the coadministration of levomepromazine. The
      extrapyramidal symptoms were not worsened by the coadministration of
      levomepromazine. These results suggest that a low dosage of levomepromazine, use
      as a sedative adjuvant to risperidone treatment, have no statistically
      significant effect on the trough plasma concentrations of risperidone.

PMID- 15744636
TI  - Naltrexone treatment of combined alcohol and opioid dependence: deterioration of
      co-morbid major depression.
AB  - Naltrexone is frequently used for the treatment of opioid or alcohol dependence.
      However, the reports on its potential to worsen affective disorders are
      contradicting. Here we report on a patient with combined alcohol and opioid
      dependence whose co-morbid major depression deteriorated reversibly and
      repeatedly under naltrexone. By exchanging buprenorphine for naltrexone, his
      depression and craving for alcohol and opioids disappeared. This underlines the
      close interaction between depression, substance dependence and the opioid system.

PMID- 15744637
TI  - Depression during therapy with interferon alpha--how long should an
      antidepressant treatment last?
AB  - Although depressive symptoms are well-known side effects of interferon alpha
      (IFNalpha), it is uncertain if these symptoms decline with the cessation of
      IFNalpha therapy. We report on a 47-year-old man who, apart from former drug
      abuse, never had suffered from a psychiatric disorder. However, he had a family
      history burdened with the suicide of his mother and his twin sister. After a
      depressive symptomatology during the IFNalpha therapy, which had been tolerably
      treated by mirtazapine, he committed a suicide attempt six months after the
      parallel termination of IFNalpha and antidepressant treatment. Two aspects of
      this case report should be emphasised. First, patients with an increased risk for
      psychiatric complications of interferon therapy must be followed closely for a
      depressive symptomatology and treated aggressively if symptoms arise. Second,
      this case report shows the relapse of depressive symptoms far beyond the end of
      the interferon treatment. If an antidepressant treatment is necessary during
      IFNalpha therapy this should not be stopped prematurely with the termination of
      the interferon medication.

PMID- 15744638
TI  - Obsessive-compulsive disorder (OCD) with psychotic symptoms and response to
      treatment with SSRI.
AB  - The co-occurrence of obsessive-compulsive and psychotic symptoms in one patient
      often represents a diagnostic problem. Distinguishing among a schizophrenic
      disorder with comorbid obsessional symptoms, an OCD with comorbid psychotic
      symptoms, or an OCD and schizophrenia or any other psychotic disorder is of
      clinical importance, since the different diagnoses have different therapeutic as
      well as prognostic implications. In the following case report we describe a
      patient who suffered from a typical OCD for more than 18 years and then developed
      clear psychotic symptoms that completely remitted after treatment with
      citalopram.

PMID- 15744639
TI  - Risperidone-associated transient diabetic ketoacidosis and diabetes mellitus type
      1 in a patient treated with valproate and lithium.
AB  - A 37-year-old man treated with valproate and lithium for bipolar affective
      disorder since 1999 and with risperidone since March 2003 was admitted to our
      clinic due to metabolic acidosis. Serum glucose was 647 mg/dL and urine ketones
      were positive. The patient was accepted as diabetic ketoacidosis (DKA).
      Risperidone, valproate, and lithium were immediately stopped, and the patient was
      treated with insulin and i.v. fluid replacement. Serum insulin and C-peptide
      levels were too low, and islet cell antibody and anti-GAD antibody were positive.
      We accepted him as type 1 diabetes mellitus (DM type 1). After the intensive
      treatment of diabetes, insulin requirements decreased gradually and diabetes
      mellitus disappeared completely within three months. CONCLUSION: Risperidone may
      lead to transient DM type 1 and DKA.

PMID- 15744640
TI  - [Patient safety].

PMID- 15744641
TI  - [Patient safety in view of specialization, minimum quantity and regionalization].
AB  - BACKGROUND: The introduction of a set of volume standards in Germany 2003 has
      lead to a discussion whether statutory volume thresholds as well as the
      enhancement of further regionalization would do more harm than good. The
      objective of this study is to evaluate the influence of specialization, volume
      standards and regionalization on patient safety. METHODOLOGY: According to study
      objectives patient safety was defined as "hospital mortality", "hospital
      morbidity", "long-term outcome" and "readmission rate". A MEDLINE analysis was
      performed using the following terms: "hospital", "volume", "outcome",
      "specialization", "regionalization", "readmission", "patient safety" and
      "review". In order to lower the high number of studies only journals published
      between 1999 and 2004 with high impact factors were used for evaluation. RESULTS:
      A vast majority of studies have been published in recent years finding
      significant higher probabilities for good outcome in high volume hospitals
      compared with low volume hospitals. However, the magnitude of the volume -
      outcome relation varies greatly among procedures and conditions, showing a strong
      and persistent relation for severe ill patients and high-risk procedures. Patient
      safety can also be influenced by surgeon volume and specialization. CONCLUSIONS:
      Specialization, volume standards and regionalization have shown to be effective
      in improving patient safety. Further studies are needed to estimate the potential
      benefits of this strategy to foster patient safety in German hospitals.

PMID- 15744642
TI  - [Quality of surgical continuing education in Germany].
AB  - BACKGROUND: One of the reasons for young doctors to leave the clinical work to go
      abroad or into non-clinical fields is insufficient quality of training under bad
      circumstances. Aim of the study was to evaluate the surgical training in Germany
      from the viewpoint of the residents. METHODS: A questionnaire was prepared by
      residents and consultants and approved by the German surgical societies (Deutsche
      Gesellschaft fur Chirurgie und Berufsverband der Deutschen Chirurgen). It was
      sent to surgical residents between June 2003 and June 2004, published in "Der
      Chirurg BDC" and distributed among residents taking part in courses conducted by
      the BDC. It could be answered anonymously by email, mail or online. RESULTS: The
      questionnaire was sent back by 584 surgical residents (about 30 % of all). 58 %
      of the residents declared that they finished the training in the intended time (6
      years). Rotation-systems as part of a structured residency program existed for 43
      %. Standard surgical procedures were discussed or explained before the procedure
      in only 46 %. 61 % of the residents were not satisfied with the teaching
      assistance by their clinical teachers in the OR. Only 33 % had regular talks with
      the Chief about their progress in surgical training. 18 % of residents felt, that
      the hospital is interested in their progress in training. Indication-conferences
      took place in 52 % and mortality-conferences in only 20 % of programs. Regular
      seminars on recent issues took place in 62 %, and 61 % of residents did not get
      financial support to attend congresses. 36 % of residents had to use their
      holidays to attend congresses. CONCLUSIONS: Surgical training structures are not
      well established in about 50 % of the training hospitals from where we got
      answers to our survey. The training potential of daily surgical work is not used
      appropriately. It is therefore imperative to develop guidelines for surgical
      training, the use of log-books and rotation-programs.

PMID- 15744643
TI  - [Minimal-invasive operative treatment of organic hyperinsulinism].
AB  - BACKGROUND: Insulinomas are small, solitary and benign endocrine pancreatic
      tumours, causing organic hyperinsulinism by autonomous insulin-secretion.
      Episodes of severe hypoglycemia and progressive obesity are the most frequent
      clinical signs. Surgical resection of the tumours is always indicated for cure.
      Because the tumours are small and surgical trauma for adequate exposure of the
      pancreas is considerable, laparoscopic techniques to approach these tumours are
      attractive. On the occasion of two cases, this report describes the laparoscopic
      treatment of these rare tumors. ANAMNESIS: Two male patients (15 years of age and
      50 years of age) were admitted for seizures and symptoms of hypoglycaemia.
      FINDINGS: During fasting tests, both were diagnosed organic hyperinsulinism, with
      a blood glucose level of 28 mg/dl, insulin of 15.9 mU/ml and a c-peptide of 1.7
      microg/l for an insulinogenic index of 0.57 determined in the young man. Similar
      values were obtained in the older man. Conventional imaging procedures were non
      diagnostic whereas endoscopic ultrasound of the pancreas revealed a 8 x 13 and 10
      x 9 mm lesion in the pancreas. THERAPY AND COURSE: Laparoscopic resection of the
      tumor was attempted and accomplished in both patients. The young man underwent
      laparoscopic enucleation of the tumor, while the 50 year old man underwent left
      sided laparoscopic resection of the pancreas because the tumor was adjacent to
      the pancreatic duct. Postoperative course was uneventful in both cases.
      CONCLUSION: It is to be expected, that this approach will receive increasing
      attention in the near future.

PMID- 15744644
TI  - [Parapneumonic effusion and pleural empyema--diagnosis and conservative therapy].

PMID- 15744645
TI  - [Pleural empyema: surgical treatment].
AB  - Pleural empyema runs in three stages, if untreated. Because it produces
      uncharacteristic signs, specific diagnosis and adequate treatment is often
      delayed. The treatment should be early, according to the stage and adapted to the
      given situation. Expenditure and morbidity of treatment are the higher the longer
      it is delayed. In the exudative stage 1, drainage--if necessary combined with
      antibiotic administration--is likely to be successful. In the fibrinous-purulent
      stage 3, often not clearly demarked from the other stages, video-assisted
      thoracoscopy (VATS) in its various forms provides the best therapeutic
      prerequisite. It makes it possible to open all cavities and free pleural layers
      from the, usually fibrinous or fibrosing, contents. Furthermore, VATS allows
      targeted drainage placement as essential precondition of effective irrigation.
      The definitive stage 3 of organization requires the technically demanding empyema
      excision or decortication.

PMID- 15744646
TI  - [Minimally-invasive surgery for inguinal hernia--pro].

PMID- 15744647
TI  - [Minimally-invasive surgery for inguinal hernia--contra].

PMID- 15744648
TI  - [What is "Fast-track"-surgery?].
AB  - "Fast-track"-surgery -- also called "fast-track"-rehabilitation -- is an
      interdisciplinary, multimodal concept to accelerate postoperative reconvalescence
      and reduce general morbidity. "Fast-track"-rehabilitation focuses on preoperative
      patient education, atraumatic and minimal-invasive access to the operative field,
      optimized anesthesia under normovolemia and prevention of intraoperative hypoxia
      and hypothermia, effective analgetic therapy without high systemic doses of
      opioids, enforced postoperative patient mobilisation, early postoperative oral
      feeding, and avoidance of tubes and drains. "Fast-track"-rehabilitation plans
      have been published for numerous operative procedures in general-, visceral-,
      vascular- and thoracic surgery, as well for orthopaedic, urological and
      gynaecological operations. Until today, "fast-track"-rehabilitation was evaluated
      most thoroughly in elective colonic surgery. Here, the multimodal regime
      decreased general morbidity from 20 - 30 % to below 10 %, while postoperative
      hospital stay was reduced from 10 - 15 to 2 - 5 days. "Fast-track"-rehabilitation
      for major surgery should be evaluated in randomised, controlled trials.

PMID- 15744649
TI  - [Endoprosthetic joint replacement].

PMID- 15744650
TI  - [Long-term results of resection arthroplasty of the metacarpophalangeal joint in
      rheumatoid arthritis].
AB  - The metacarpophalangeal arthroplasty in rheumatoid arthritis reported is a
      modification of the Vainio-Arthroplasty. The main difference of the technique is
      the fixation of the proximal extensor tendon to the palmar plate, better to the
      ligamentum metacarpeum transversum profundum. The more flexion of the
      metacarpophalangeal joint the more reposition of the joint is achieved. The long
      term results of 30 arthroplasties of the metacarpophalangeal joint are presented
      in a prospective study. The cases were followed for 10.5 to 14.5 years (average
      11.6 years). Marked release of pain was found in all patients. 75 per cent of the
      patients reported functional improvement of their hand at a score of "good" or
      "very good". The postoperative movement was 70 degrees on an average. In summary,
      the resection arthroplasty of the metacarpophalangeal joints produces very good
      function and correction of the ulnar deviation and palmar luxation of the MCP
      joints. The arthroplasty is a real alternative to the total endoprosthetic
      replacement of metacarpophalangeal joints in rheumatoid arthritis.

PMID- 15744651
TI  - [The WEKO finger joint prosthesis].
AB  - The WEKO prosthesis was developed between 1989 and 1993 in order to restore
      stability and function of destroyed metacarpophalangeal joints in rheumatoid
      arthritis. The prosthesis is a hinged one and is fixed to the bone cementlessly
      by special osseointegrated sleeves in which the stem of the implant is fastened
      by a cone. Forty-eight patients with 74 prosthesis have been operated on in 1993.
      In a follow-up study in 2003, 43 of them (89.5 %) with 65 prostheses (87.8 %)
      could be re-examined clinically and radiographically. In seven patients (16.2 %)
      implant arthroplasty failed comprising loosening of the prosthesis within their
      sleeves, loosening of the sleeves in the bone and implant breakage. Twelve
      implants (16.2 %) had to be removed. The range of motion at follow-up was 0/10/70
      degrees in comparison to 0/0/90 degrees postoperatively. Patients satisfaction
      over the first three to four years was higher than later due to deterioration of
      the rheumatoid disease. Thus, classical handscores to assess the outcome could
      not be applied. A second generation of the WEKO prosthesis was developed to
      improve rotational stability and osseointegration paying attention to reports
      concerning failures which were seen also by other authors. The stem of the
      implant was changed to a cylindrical one with star shaped cross-section which
      allows some pistoning in order to reduce the stressload of the sleeves.

PMID- 15744653
TI  - [Results after arthroplasty of the metacarpophalangeal joints with uncemented,
      unconstrained HM prosthesis in rheumatoid patients].
AB  - PURPOSE: In 80 % of patients with rheumatoid arthritis, the metacarpophalangeal
      (MP) joints are involved with increasing destruction and loss of function.
      Silicone arthroplasty of the MP joints leads to a limited range of motion, an
      increase in osteolysis and fractures of the implants. The cementless,
      unconstrained design of the HM prosthesis is a new concept for replacing the MP
      joints of rheumatoid patients. Short-term and midterm results are shown. METHOD
      AND MATERIAL: In a prospective study, 38 HM prostheses were implanted, 28 in
      patients with rheumatoid arthritis, four with osteoarthrosis, five with
      polyarthrosis and one after revision of a silicone implant. The patients were
      reexamined clinically and radiologically after an average follow-up of 16 months
      (6 - 37 months). RESULTS: The average active range of motion for extension,
      flexion increased from 0/15/65 degrees before surgery to 0/9/65 degrees after
      surgery. The remaining ulnar drift was 12 degrees (preoperative 18 degrees ). The
      average grip strength after surgery was 80 % of the opposite side. Pain in the
      verbal analog scale improved from 2.3 to 1.7 postoperatively. One palmar
      subluxation of an implant of the little finger was recognized. No infection
      occurred. The X-rays showed complete osteointegration in all metacarpal
      components. Radiolucent zones were found in progress only at the basis on the
      phalangeal components without radiological signs of loosening or sinking.
      CONCLUSION: The short- and midterm results after implantation of the cementless,
      unconstrained HM prosthesis show an improved hand function and pain relief. The
      design of the implant may solve the accepted postoperative problem of instability
      of the MP joints. Until now, no prosthesis had to be exchanged.

PMID- 15744652
TI  - [Early results of NeuFlex silastic implant in MCP arthroplasty].
AB  - For the reconstruction of destroyed metacarpophalangeal (MP) joints in rheumatoid
      arthritis, the Swanson silicon spacer is still the golden standard. However, long
      term follow-up reveals an increasing number of complications, particularly
      mechanical failure. In order to deal with these problems a number of new,
      biomechanically different silicone implants have been designed. Among these, the
      NeuFlex prosthesis has a preflexed hinge of 30 degrees in relation to the shaft
      axis, a more palmar lying center of rotation and a rectangular hinge with a
      collarlike platform against the bony surfaces. In a prospective study, the early
      results of the first thirteen patients operated with the NeuFlex arthroplasty are
      reported. All patients suffered from rheumatoid arthritis with destruction of the
      MP joints. The mean follow-up was 12.3 months. A total of 37 joints were
      replaced. All patients were female with an average age of 56 years. Postoperative
      reduction of pain, measured on a visual analog scale with the maximum of 10
      (VAS), decreased from 6.6 to 0.7 (p < 0.001). Jamar grip strength improved from
      4.2 kg preoperatively to 9.9 kg postoperatively (p < 0.005). Range of motion
      improved from 37 degrees to 57 degrees (p < 0.0001) as a result of a reduction in
      active extension deficit which reduced from 35 degrees to 15 degrees
      postoperatively. Ulnar drift was reduced from 20.2 degrees to 3.4 degrees at
      follow-up (p < 0.005). Radiological evaluation showed no implant failure, no
      subsidence, and no signs of inflammatory reaction. Overall the NeuFlex silicone
      implants show encouraging early results which must be confirmed in the long term.

PMID- 15744654
TI  - [Early results of proximal interphalangeal joint replacement with pyrolytic
      carbon prosthesis (Ascension) in idiopathic and post-traumatic arthritis].
AB  - Surgical treatment of painful idiopathic and post-traumatic arthritis with joint
      replacement of the proximal interphalangeal joint has become increasingly
      important. Due to shortcomings of former constrained and partially constrained
      prostheses with regard to abrasion and durability we have been using an
      unconstrained prosthesis since April 2002. This model is an almost abrasion free,
      biocompatible 2-component prosthesis. The surface is shaped like the condyles and
      the position is secured in a press-fit technique. During October 2004 we reviewed
      the results of 20 out of 29 patients with idiopathic or post-traumatic arthritis
      who had been treated with a pyrolytic carbon proximal interphalangeal joint
      prosthesis from April 2002 to April 2004 retrospectively. Clinical, subjective
      and radiological parameters were studied. On follow-up after 0.5 to 2.5 years the
      patients were satisfied with the pain relief. The range of motion varied.
      However, with an average ROM of 50 degree it was equivalent to the results in
      literature. Signs of periprosthetic cysts, osteophytes and loosening of the
      proximal as well as of the distal component could be seen in the radiograms of
      some patients. There was no correlation between these radiological observations
      and range of motion, pain or grip strength. In three cases the joint prosthesis
      had to be converted to an arthrodesis of the proximal interphalangeal joint.
      Bearing in mind the correct indications (intact collateral ligaments, stable bone
      stock and sufficient extensor and flexor tendons), pyrocarbon prosthesis are a
      treatment option for idiopathic and posttraumatic arthritis preserving motion and
      reducing pain. Radiological results seem to indicate an absence of
      osteointegration and tension forces at the prosthesis/bone interface. Further
      investigation will be necessary to improve surface and design to increase
      radiological results in long-term follow-up. Additional surveys are required to
      improve indications, surgical approach and intraoperative control of correct
      component positioning.

PMID- 15744656
TI  - [Hand surgery in musicians with rheumatoid arthritis].
AB  - Hand surgery in musicians and hand surgery of the rheumatoid hand are main
      subjects, beside others, of the Hand Surgical Department of the DRK-Clinic in
      Baden-Baden/Germany, clinically as scientifically, too. There are some special
      aspects of surgery of the hand in musicians with rheumatoid arthritis. Between
      1980 and 2001, seven musicians with this inflammatory disease (3.8 % of all 185
      musicians, gathered up to April 2001 in our musician's data bank) did seek help.
      Among these patients, we performed surgery in five musicians (four professionals,
      one semi-professional), but altogether 18 operations have been performed in these
      five musicians. Three of these five musicians were able to continue their
      original musical activity for many years despite their rheumatoid arthritis, one
      of them switched from soloist to teaching activity, one we lost to follow up. In
      musicians, individual considerations about the indication, the type of surgery
      and its details must be made pre-operatively. These may depend upon the
      instrument played and which hand or finger is affected. If possible, the expected
      results of surgery should be assessed during a preoperative recitation, using
      static or dynamic test-splints or plasters and having the musician play with
      these external devices.

PMID- 15744655
TI  - [Synovialectomy of the metacarpophalangeal joints with reconstruction of the
      radial collateral ligaments -- long-term results in patients suffering from
      rheumatoid arthritis].
AB  - Rheumatoid arthritis may lead to destruction of MP joints and severe alteration
      of grip and other hand functions. Due to the improvement in medical treatment,
      synovialectomy of the MP joints is necessary only in late stages. Most centres
      prefer alloarthroplasties in late stages, as erosion of the cartilage and
      loosening of the ligaments have already led to destruction of the MP joints and
      destabilization of grip functions. We do not use alloarthroplasties as our first
      choice, but pay special attention to the reconstruction of the radial collateral
      ligaments. Therefore, the elongated radial ligaments are detached near their
      origin after synovialectomy of the dorsal aspects of the MP joint. After
      detachment of the radial ligament, the palmar aspects can be cleaned easily. The
      radial collateral ligaments are shortened and reinserted dorsally to gain slight
      supination. This study shows the long-term results of our patients. In a period
      of ten years, 74 patients (87 hands, 347 MP joints) were reexamined after an
      average of 55 months postoperatively. The loss of active motion was 18 degrees
      and ulnar deviation could be reduced from 25 degrees to 7 degrees. 71 % of the
      joints showed stable ligaments, 14 % loose, 15 % unstable ligaments. We saw
      recurrence of synovialitis in 18 % (10 % mild, 7 % significant, 1 % severe).
      Radiographs showed amelioration in 14 % of cases and deterioration in 39 %. There
      was no correlation between active range of motion, synovialitis and X-rays.
      Results were constant when compared with exams before and five years after
      surgery. Our investigation shows good and stable results, which can be easily
      compared with the outcome of other studies after alloarthroplasty. The main
      advantage in our procedure is the easy access to all parts of the MP joint, which
      allows complete synovialectomy. By shortening and reinserting the elongated
      radial collateral ligament, we achieve a mild supination and amelioration of grip
      strength. The results are constant in long terms. In case of recurrent
      synovialitis or loosening of the ligaments any other type of auto- and
      alloarthroplasties can still be performed.

PMID- 15744657
TI  - [Aims of hand therapy in treatment of rheumatoid hand].
AB  - When dealing with rheumatoid arthritis, the main issues of hand therapy are the
      treatment of hand and finger joints. We emphasize mobilisation of joints, muscle
      strengthening, correcting deformities by low temperature splints and joint
      protection. Further tasks of occupational therapy are: Informing patients about
      adaptive devices and training their use as well as educational programs for
      patients with reduced mobility of the upper limb. The most common surgery on the
      rheumatoid hand, that need postoperative treatment by a hand therapist are
      complete and limited arthrodesis of the wrist, surgical reconstruction of
      tendons, arthroplasty and arthrodeses of and for finger joints, and so on. At the
      Nordwestdeutsches Rheumazentrum St. Josef-Stift Sendenhorst we have designed a
      standard postoperative management for treating arthroplasty with a
      "Silikonspacer" in the metacarpophalangeal joints.

PMID- 15744658
TI  - [Occupational therapy after rheumatoid hand surgery].
AB  - Occupational therapists face a number of challenges in the after-treatment of
      rheumatoid hand surgery. They have to take into account the specialties of the
      surgery and the remaining deformities of the rheumatoid hand. Edema prophylaxis
      and scar treatment are similar for all patients, while splinting and functional
      training depend greatly on the different kinds of surgery. Both splinting and
      mobilization have to be adjusted to patient and process of the therapy. The
      protracted treatment requires a high compliance of the patient. Instruction and
      information about operation and postoperative therapy support comprehension and
      cooperation of the patient.

PMID- 15744659
TI  - [Commentary on the article of C. Smola: about the problem of radial tunnel
      syndrome or "where does the tennis elbow end and where does the radial tunnel
      syndrome begin?"].

PMID- 15744661
TI  - From eggs to fossils: epigenesis and transformation of species in Pander's
      biology.
AB  - Christian Heinrich Pander (1794-1865), a Russian scientist of German culture, is
      known for his epoch-making work in embryology, as well as for his important
      contributions to palaeontology. Indeed he viewed embryonic development and the
      history of the earth as two aspects of one and the same essential phenomenon,
      namely, a perpetual metamorphosis affecting the living world on different scales.
      He viewed embryology as a gradual, epigenetic transformation (as opposed to
      preformation) with an intermediary stage, the formation of simple germ-layers. As
      early as 1821, he argued more generally that species themselves transform under
      the influence of certain environmental factors. Pander thus embodies the very
      close link that existed between the triumph of epigenesis and the expansion of
      transformist theories in the early 19th century.

PMID- 15744662
TI  - Putting evo-devo into focus. An interview with Scott F. Gilbert. Interview by
      Alexander T. Mikhailov.
AB  - This article announces Dr. Scott F. Gilbert as the winner of the Alexander
      Kowavelsky international prize (2004) and briefly reviews his achievements in
      developmental biology and evo-devo. Dr. Gilbert replies to the interviewer's
      questions concerning his personal interest in evo-devo and current controversies
      within the field. His thoughts and comments represent a unique blend of research
      talents and skills, curiosity and creativity.

PMID- 15744664
TI  - Transforming growth factor beta 2 promotes the formation of the mouse
      cochleovestibular ganglion in organ culture.
AB  - The inner ear structures are derived from the otic vesicle (OV) which is formed
      by thickening and invagination of the otic placode of the surface ectoderm. A
      number of neuroblasts, which arise from epithelial cells of the otic vesicle,
      delaminate and differentiate into neurons of the cochleovestibular ganglion
      (CVG). We have found that transforming growth factor-BEta2 (Tgfbeta2 ) was
      expressed in the otic epithelium at the OV stages between Embryonic days (E) 9.5
      and 11.5 and that anteroventrolateral localization of its expression in the OV
      overlapped with that of NeuroD, which is a marker of delaminating CVG precursors.
      The expression of TGFbeta type I and type II receptors in the otic epithelium and
      the nuclear localization of phosphorylated-Smad2 in both the otic epithelium and
      CVG suggested that TGFbeta2 signaling plays some roles in CVG formation. In order
      to examine the roles of TGFbeta2 in differentiation of the inner ear, otic
      vesicle explants of E10.5 mouse embryos were treated in vitro with TGFbeta2 or
      the TGFbeta type I receptor kinase inhibitor, SB431542. Addition of TGFbeta2
      peptide to the culture led to Enlargement of the CVG, while the inhibitor reduced
      its size. These findings strongly imply that TGFbeta2 contributes to the
      development of the CVG in mouse embryos.

PMID- 15744663
TI  - Delivery of germinal granules and localized RNAs via the messenger transport
      organizer pathway to the vegetal cortex of Xenopus oocytes occurs through
      directional expansion of the mitochondrial cloud.
AB  - During Xenopus oogenesis, the message transport organizer (METRO) pathway
      delivers germinal granules and localized RNAs to the vegetal cortex of the oocyte
      via the mitochondrial cloud (Balbiani body). According to the traditional model,
      the mitochondrial cloud is thought to break up at the onset of vitellogenesis and
      the germinal granules and METRO-localized RNAs are transported within the
      mitochondrial cloud fragments to the vegetal cortex of the oocyte. We used light
      and electron microscopy in situ hybridization and three-dimensional
      reconstruction to show that germinal granules and METRO-localized RNAs are
      delivered to the oocyte cortex before the onset of mitochondrial cloud
      fragmentation and that the delivery involves accumulation of localized RNAs and
      aggregation of germinal granules at the vegetal tip of the mitochondrial cloud
      and subsequent internal expansion of the mitochondrial cloud between its animal
      (nuclear) and vegetal tips, which drives the germinal granules and METRO
      localized RNAs toward the vegetal cortex. Thus the fragmentation of the cloud
      that occurs later in oogenesis is irrelevant to the movement of METRO-localized
      RNAs and germinal granules. On the basis of these findings, we propose here a
      revised model of germinal granule and localized RNAs delivery to the oocyte
      vegetal cortex via the METRO pathway.

PMID- 15744665
TI  - Loss of beta 1 integrin function results in upregulation of connexin expression
      in embryonic stem cell-derived cardiomyocytes.
AB  - We show that loss of beta1 integrin function affects connexin (Cx) expression in
      embryonic stem (ES) cell-derived cardiomyocytes. Both loss of beta1 integrin
      function and inhibition of integrin clustering by RGD peptides in wild type ES
      cells correlated with upregulated expression of gap junctional proteins in ES
      derived cardiomyocytes. The upregulation of connexin transcript levels in beta1
      integrin-deficient cells is paralleled by a higher fraction of cells co
      expressing Cx40 and Cx43. These observations demonstrate that the expression of
      connexins in developing cardiomyocytes is correlated to integrin-dependent
      mechanisms. Further, we found that upregulated cardiac connexin expression in
      beta1 integrin-deficient cells is related to Rho- and Wnt-dependent pathways.
      beta1 integrin-deficient cardiac cells displayed high levels of cytoplasmic gamma
      and beta-catenins throughout the differentiation period. The administration of
      lithium, an activator of beta-catenin-dependent pathways, resulted in up
      regulated connexin mRNA levels in wild type cardiomyocytes at intermediate, but
      not at early stages, indicating that the effects are restricted to advanced
      stages of cardiac differentiation. On the other hand, inhibition of Rho-dependent
      integrin signaling by treatment of cardiac cells with exoenzyme C3 resulted in
      immediate up-regulation of cardiac connexin transcript levels at early
      differentiation stages. Our data indicate that integrin function affects connexin
      expression in cardiomyocytes via direct effects on RhoA-dependent signaling
      mechanisms at early differentiation stages and of beta-catenin/Wnt-dependent
      pathways at advanced stages.

PMID- 15744666
TI  - Developmental expression of the high mobility group B gene in the amphioxus,
      Branchiostoma belcheri tsingtauense.
AB  - High-Mobility Group (HMG) B proteins are abundant and highly conserved non
      histone proteins, which play an important architectural role in the assembly of
      nucleoprotein complexes and in the Regulation of transcription. These proteins
      have also been shown to play key roles during embryonic development and cell
      differentiation. Here we report a full-length cDNA sequence of the HMG protein,
      AmphiHMGB from Amphioxus. Sequence analysis indicates that this putative
      AmphiHMGB protein contains four domains: HMG-box A, HMG-box B, basic region,
      acidic carboxyl-terminal tail and a linker. Phylogenetic analysis suggests that
      AmphiHMGB falls outside the vertebrate clade. HMGB gene duplication occurred near
      the base of the vertebrate gene Clade. The dynamic expression of AmphiHMGB during
      embryonic development reveals for the first time that it may involve
      differentiation of neural ectoderm, mesoderm and endoderm in this animal.

PMID- 15744667
TI  - A generalized caspase inhibitor disrupts early mammalian development.
AB  - The role and mechanism of cell death in early mammalian embryos is not well
      understood. In mouse embryos collected after fertilization and maintained in
      vitro until blastula formation, two instances of cell death are observed: the
      polar bodies and one or two cells near the equator, at the junction of the inner
      cell mass to the prototrophoblast. Inhibitors of caspases do not block the death
      of the polar bodies. Inhibitors of caspases 3, 7 and 8 do not affect post
      cavitation death, but the pan-caspase inhibitor zVAD-FMK, when applied at the 1-2
      cell stage, causes an expansion of post-cavitation death and ultimately
      malformation or death of the embryo. Our results indicate that the early deaths
      are not caspase-dependent and that there is a role for caspase activity in early
      embryos, which is not related to cell death.

PMID- 15744668
TI  - The Fox gene family in Xenopus laevis:FoxI2, FoxM1 and FoxP1 in early
      development.
AB  - We here describe the sequences and expression patterns of three new Fox (fork
      head box) transcription factors in Xenopus laevis embryos. xlFoxI2, another
      member of subclass I, is maternally transcribed. Zygotic transcripts are first
      detected during neurulation and become localised to the dorsal part of
      epibranchial placodes. xlFoxM1 like xlFoxP1 are the first members of subclasses M
      and P described in Xenopus. Both genes are maternally expressed and transcripts
      are found during early cleavage stages in the animal blastomeres. xlFoxM1 is
      strongly upregulated during neurula stages and transcripts are localised in the
      neuroectoderm. Later, expression is found in the spinal cord, the
      rhombencephalon, the retina and in the branchial arches. xlFoxP1 is activated
      during organogenesis and is mainly expressed in the brain, head mesenchyme and in
      the splanchnic layer of the lateral plate mesoderm.

PMID- 15744669
TI  - Developmental expression of Pod 1 in Xenopus laevis.
AB  - The basic helix-loop-helix transcription factor, Pod 1, has been shown to be
      expressed in the mesenchyme of many developing mouse organs, including the heart,
      lungs and gut. In the kidneys of developing mice, Pod 1 is highly expressed in
      the condensing metanephric mesenchyme, differentiating and late stromal cells and
      in developing podocytes. We have obtained an EST (CF270487) which contains the
      Xenopus laevis Pod 1 sequence. Conceptual translation of the Xenopus laevis Pod 1
      sequence shows approximately 85% similarity to other vertebrate homologues. RT
      PCR indicates that expression is initiated at stage 13 and increases
      differentially in the developing pronephros compared to the whole embryo. RT-PCR
      of a kidney dissection at stage 42 shows higher expression in the glomus than in
      the tubule or duct. In situ hybridisation analysis at tail bud stages shows the
      anterior-most branchial arch and pronephric glomus are intensely stained. At
      stage 40, staining persists in the glomus and in the epicardium region of the
      heart. Adult organ analysis shows expression is highest in the rectum and the
      spleen, with significant expression in the duodenum, heart, kidney, lungs,
      pancreas, skin, liver and muscle.

PMID- 15744670
TI  - Entactin and laminin gamma 1-chain gene expression in the early chick embryo.
AB  - The expression patterns of entactin and laminin gamma1 chain genes were examined
      by in situ hybridization of their mRNAs in the early chick embryo from stage X
      (morula) to stage HH10-11 (10-somites). The entactin and laminin gamma1
      transcripts were found in abundance in the embryo at stage X. Entactin
      polypeptides were detected in embryos at stage X by immunoprecipitation. The
      expression of the laminin transcripts was intense and of entactin milder in the
      epiblast and in the hypoblast of embryos at stage XIII (blastula). During
      gastrulation (stage HH3-4), the laminin gamma1 and entactin cRNAs gave strong
      signals in the cells ingressing through the primitive streak, in the migrating
      mesenchymal cells and the cells of the lower layer. At the neurula stage (stage
      HH5-6), punctate groups of cells expressed laminin gamma1 strongly in the neural
      ectoderm, while the signal of expression was milder and more uniform in
      chordamesoderm. The entactin cRNAs gave a strong punctate pattern of mRNA
      expression in the neural ectoderm, in mesoderm and in endoderm in embryos at the
      late gastrula stage (HH4), but mRNA expression was mild in the neural plate and
      in mesoderm and gave no signal in endoderm and lateral ectoderm in embryos at
      stage HH6 (neurula). At the 10-somite stage, the laminin gamma1 cRNAs gave strong
      signals in the neural tube and in neural crest cells migrating along the neural
      tube ventrally and low signals in ectoderm, intense signals in the myotome and
      milder signals in the dermatome and sclerotome of somites and intense signals in
      the mesonephric tubules. The punctate pattern of entactin expression was notable
      in cells at all stages studied. Ubiquitous expression of laminin gamma1 and
      entactin genes during the morula and blastula stages becomes restricted to
      specific cell populations as the first cell commitments start.

PMID- 15744671
TI  - Selective predation and productivity jointly drive complex behavior in host
      parasite systems.
AB  - Successful invasion of a parasite into a host population and resulting host
      parasite dynamics can depend crucially on other members of a host's community
      such as predators. We do not fully understand how predation intensity and
      selectivity shape host-parasite dynamics because the interplay between predator
      density, predator foraging behavior, and ecosystem productivity remains
      incompletely explored. By modifying a standard susceptible-infected model, we
      show how productivity can modulate complex behavior induced by saturating and
      selective foraging behavior of predators in an otherwise stable host-parasite
      system. When predators strongly prefer parasitized hosts, the host-parasite
      system can oscillate, but predators can also create alternative stable states,
      Allee effects, and catastrophic extinction of parasites. In the latter three
      cases, parasites have difficulty invading and/or persisting in ecosystems. When
      predators are intermediately selective, these more complex behaviors become less
      important, but the host-parasite system can switch from stable to oscillating and
      then back to stable states along a gradient of predator control. Surprisingly, at
      higher productivity, predators that neutrally select or avoid parasitized hosts
      can catalyze extinction of both hosts and parasites. Thus, synergy between two
      enemies can end disastrously for the host. Such diverse outcomes underscore the
      crucial importance of the community and ecosystem context in which host-parasite
      interactions occur.

PMID- 15744672
TI  - Training competent minimal access surgeons: review of tools, metrics, and
      techniques across the spectrum of technology.
AB  - Technology has transformed the face of surgical technique among the disciplines
      of surgery. This revolution has created a strong demand from the public for the
      availability of minimally invasive surgical (MIS) interventions. Significant
      pressure has been placed on both industry and medicine to develop, test, and
      implement devices and procedures at a rapid pace. Unfortunately, this pace has at
      times surpassed the system's ability to train and prepare a corps of surgeons
      competent in both the technical and cognitive aspects of minimal access surgery.
      The economic constraints of surgical practice, coupled with recently introduced
      work-hour restrictions, have made the delivery of minimally invasive surgical
      education a challenging endeavor. Much work has been done in academic and private
      institutions to address this need. Solutions traversing the spectrum of
      technology have been developed, tested, and implemented in training. The purpose
      of this review is to highlight these solutions on the basis of their validity,
      utility, and overall contribution toward achieving the goal of producing
      competent minimally invasive surgeons. The body of literature suggests multiple
      valid training and assessment constructs exist. However, the overall utility of
      many validated "high-end" training technologies is limited by cost and access.
      Efforts should be aimed at creating valid training and assessment paradigms that
      can be applied by the broadest group of trainees, from medical students to
      surgeons, in active practice.

PMID- 15744673
TI  - Vaccine therapy for cancer: fact or fiction?
AB  - Great strides in the understanding of regulation of the immune system have led to
      development of strategies to harness the potential of cellular immune responses
      for improving the outcome for cancer patients. To generate a cytotoxic T
      lymphocyte (CTL) response to cancer cells requires tumor-specific antigens
      processed appropriately and displayed by major histocompatibility complex (MHC)
      molecules, T-lymphocytes with receptors of appropriate specificity, and co
      stimulation delivered by antigen-presenting cells through members of the B7
      family. In this review, the fundamental advances that have been made in tumor
      antigen discovery, and the novel vaccine approaches arising from these advances
      are discussed.

PMID- 15744674
TI  - Preoperative risk factors for postoperative Staphylococcus aureus nosocomial
      infections.
AB  - Of the 40 million patients who undergo surgery each year in the United States,
      20% may develop a postoperative nosocomial infection. Staphylococcus aureus (S.
      aureus) is the most common organism involved, and carriage of S. aureus in the
      anterior nares has been identified as a risk factor for these infections. Topical
      mupirocin applied to the anterior nares has been successful in eliminating S.
      aureus and decreasing nosocomial infections due to S. aureus. Concurrent use of
      preoperative chlorhexidine showers may further reduce the incidence of S. aureus
      surgical site infections (SSIs). In addition to treating the patient, active
      surveillance programs to eliminate nasal colonization in hospital surgical
      personnel have controlled outbreaks of S. aureus SSIs. Recently, a large study
      identified risk factors linked to S. aureus nasal colonization, which included
      obesity, male gender, and a history of a cerebrovascular accident. Protective
      factors included older age, current smoking, and alcohol use. Thus, by modulating
      these variables, investigators may create interventions aimed at reducing S.
      aureus nasal carriage and ultimately, postoperative nosocomial infections.

PMID- 15744675
TI  - Method for creating ideal tissue fusion in soft-tissue structures using radio
      frequency (RF) energy.
AB  - Bipolar radiofrequency (RF) energy can successfully seal vascular structures up
      to 7 mm by fusing collagen and elastin in the lumen. Valleylab has created a
      system to expand this technology beyond vessel sealing with the development of a
      closed-loop, feedback-control RF generator that closely monitors tissue fusion.
      This generator, operating with a loop time of approximately 250 micros,
      continuously adjusts energy output, creating optimized soft-tissue fusion through
      structural protein amalgamation. In the first study, RF energy was applied to
      canine lung using the new-generation generator and lung-prototype device. A
      lobectomy was completed, sealing the lobar bronchus, parenchyma, and pulmonary
      vasculature. Chronic performance of the seals was evaluated at necropsy on
      postoperative days 7 and 14. In a second study, RF energy was applied to porcine
      small intestine using the same closed-loop generator and anastomosis prototype
      device. Acute tissue fusion was assessed qualitatively for hemostasis and seal
      quality. Terminal tissue evaluation was completed on postoperative day 7 and
      analyzed histopathologically. Histopathology confirmed acute and chronic tissue
      fusion in both the lung and intestine. Normal pathological healing was
      substantiated by angiogenesis, granulation, and proliferation of fibroblasts.
      Preliminary studies using canine lung and porcine small intestine demonstrate the
      potential of this closed-loop generator for soft-tissue amalgamation. Advanced
      monitoring capabilities make this fusion system applicable in many soft-tissue
      structures with adequate collagen and elastin. Further investigation of potential
      surgical applications needs to be completed.

PMID- 15744676
TI  - Staple-line reinforcement techniques with different buttressing materials used
      for laparoscopic gastrointestinal surgery: a new strategy to diminish
      perioperative complications.
AB  - Many techniques have been analysed to reduce the risk of perioperative
      anastomotic leakage and bleeding. No specific resection technique with either
      linear or circular stapling devices has been shown to be superior in preventing
      these complications. Reinforcement of staple lines with various buttressing
      materials is a new strategy used to diminish or eliminate anastomotic leaks and
      haemorrhage. In this chapter, varying reinforcement techniques with different
      materials are compared. The available literature has been reviewed thoroughly for
      relevant data regarding stapled reinforcement techniques and minimizing
      anastomotic leaks and haemorrhage. Reported data show non-absorbable, semi
      absorbable, and bioabsorbablematerials available for gastrointestinal (GI)
      resections. Semi-absorbable xenomaterials (Bovine Pericardial Strips and Bovine
      Collagen Strips; Shellhigh No-Reaction Vascupatch, Milburn, NJ, USA), non
      absorbable expanded polytetrafluoroethylene (ePTFE; W.L. Gore, Elkton, MD, USA)
      and absorbable poly (L-lactic acid-co-epsilon-caprolactomne) film are compared.
      Non-absorbable and semi-absorbable materials show many differences. Absorbable
      polymer membranes demonstrate marked benefits. Staple-line reinforcement used for
      laparoscopic GI surgery is a relatively new strategy, most probably improving
      perioperative outcome only if proper buttressing material is used. To decrease
      anastomotic complications, using an absorbable polymer membrane as staple-line
      reinforcement material is reliable and efficacious.

PMID- 15744677
TI  - New hemostatic agents in general open and laparoscopic surgery.
AB  - F ollowing tissue disruption, whether operative or traumatic, the priorities of
      any organism are cessation of hemorrhage, prevention of infection, and
      restoration of tissue integrity and function. Several hemostatic techniques
      achieve the goal of hemorrhage cessation. One evolving technique is the use of
      fibrin sealants (FSs) as a surgical tissue adhesive. The different and most
      common applications of fibrin glue in open and laparoscopic surgery are reviewed.

PMID- 15744678
TI  - Recent advances in techniques of liver resection.
AB  - The role of liver resection for benign and malignant hepatobiliary diseases is
      expanding because of the markedly reduced operative mortality in recent years, as
      the result of better patient selection, improved surgical techniques, and better
      perioperative management. The major technical challenge of liver resection is
      control of bleeding during transection of liver parenchyma. Ultrasonic dissector
      and clamp crushing are the two techniques used most frequently in liver
      transection. In recent years, new instruments have been developed for liver
      transection with an aim to reduce bleeding. Other important advances in liver
      surgery that have contributed to improved perioperative outcomes include
      intraoperative ultrasound (IOUS), use of vascular staplers, and reduced bleeding
      by the development of low central venous pressure anesthesia. Laparoscopy is
      useful for staging purposes, and laparoscopic liver resection is gaining
      popularity due to the availability of new laparoscopic instruments for liver
      transection. Development of local ablative therapies for liver tumors, such as
      radiofrequency (RF) ablation, is posing a competition to liver resection.
      However, such techniques also have allowed expansion of indication for hepatic
      resection to patients with bilobar tumors, and thermal ablative technologies have
      been used for liver transection. This chapter reviews the current techniques of
      liver resection.

PMID- 15744679
TI  - New advances in laparoscopic treatment of morbid obesity.
AB  - The prevalence of obesity in the United States (U.S.) is increasing to epidemic
      proportions. Currently, more than 60% of Americans and 51% of Germans are
      overweight. Whereas a variety of medications are available for treatment of
      obesity, none results in the long-term loss of more than 10% of body weight. The
      current standard for treatment of severe obesity, defined as a body mass index
      (BMI) of greater than 35 kg/m2 with comorbidities and generally greater than 40
      kg/m2, is surgical. Several surgical procedures are currently available,
      including gastric bypass, biliopancreatic diversion (BPD) with duodenal switch,
      and the adjustable gastric band. These operations may be performed using
      laparoscopic surgical techniques to minimize perioperative morbidity and
      postoperative recovery time. To optimize the outcome of this type of procedure,
      bariatric surgery should be performed on carefully selected patients, in
      bariatric centers specially equipped to care for the obese, within a broadly
      based, multidisciplinary setting that provides lifelong postoperative care.

PMID- 15744680
TI  - Laparoscopic surgery for colon and rectal cancer.
AB  - Use of laparoscopic resection for colorectal malignancy has raised concerns
      regarding local cancer control and the lack of long-term results. Most reported
      data are preliminary and medium-term results, at best. The aim of this study is
      to analyse all patients who underwent a laparoscopic resection for colorectal
      cancer at our department between November 1992 and July 2003. The cohort
      comprised a total of 394 patients (194 rectal cancer and 200 colon carcinoma).
      The most common procedures were high and low anterior resection with total
      mesorectum excision (TME) (176), followed by sigmoidectomy (89), right
      hemicolectomy (57), and left hemicolectomy (42). Mean operating time was 176
      minutes. Conversion was necessary in 4 of the patients. Mean number of lymph
      nodes removed was 27. The postoperative complication rate was 20.1% (rectum) and
      12.5% (colon). One patient died of myocardial infarction. Mean follow up was 45
      (0.3-135) months. Port site metastasis occurred in 2 patients. The local
      recurrence rate was 4.1% after curative rectum resection and 0.5% in the colon
      group. After curative resection, the overall 5-year survival rate was 76.9%
      (rectum), and 81.4% (colon). Cancer-related survival rate after 5 years was 87.7%
      (rectum), and 91.3% (colon). Our results demonstrate that laparoscopic resection
      for colorectal cancer is not associated with higher morbidity and mortality
      rates. Established oncological principles are respected and long-term results are
      at least as good as those after open surgery.

PMID- 15744681
TI  - The SECCA procedure: a new therapy for treatment of fecal incontinence.
AB  - The SECCA (Curon Medical, Freemont, CA USA) device delivers temperature
      controlled radiofrequency (RF) energy to the anorectal junction to treat fecal
      incontinence. The procedure is performed as an outpatient either in the endoscopy
      suite or ambulatory surgery center. After appropriate local block, the SECCA
      device is then inserted into the anal canal and submucosal RF energy is delivered
      circumferentially to the anorectal junction. A pilot trial in Mexico on 10
      patients demonstrated a significant improvement in Cleveland Clinic Florida Fecal
      Incontinence Scores (CCF-FIS) from a pre-treatment score of 13.5 to 12-month post
      treatment score of 3.8. These patients continued to have significantly improved
      continence with an average CCF-FIS of 7.3 at 24-month follow up. A multi-center,
      institutional review board-approved, open label, prospective trial that evaluates
      the efficacy and safety of the SECCA procedure has been completed in the United
      States (U.S.). Five centers prospectively enrolled 50 patients with greater than
      or equal to 3 months of weekly fecal incontinence who also had failed either
      medical or surgical interventions. Patients underwent anoscopy, anorectal
      manometry (ARM), endoanal ultrasound (EAUS), and pudendal nerve terminal motor
      latency (PNTML) at 0 and 6 months. The CCF-FIS scale, fecal incontinence-related
      quality of life score (FIQL), and SF-36 were administered at 0, 3, and 6 months.
      After conscious sedation and local perianal block, RF energy was delivered by way
      of the SECCA device. At 6 months, the mean CCF-FI score improved significantly
      (14.5 to 11.1, p<0.0001). All FIQL parameters improved: lifestyle (2.5 to 3.1,
      p=0.0001), coping (1.9 to 2.3, p=0.005), depression (2.8 to 3.1, p=0.0008),
      embarrassment (1.9 to 2.5, p<0.0001). Sixty-percent (n=30) of the patients
      improved after therapy, with 70% resolution of their symptoms. The SF-36 mental
      composite score (45.3 to 48.3, p=0.06) and social function sub-score (64.0 to
      77.3, p=0.003) improved. No changes occurred in ARM, EAUS, or PNTML. Two major
      complications included two mucosal ulcerations. From these data, the authors
      concluded that RF energy delivered for treatment of FI safely improves CCF-FIS,
      FIQL, and quality of life.

PMID- 15744682
TI  - Permanent sterilization for the 21st century using the hysteroscopic approach.
AB  - Transcervical hysteroscopic permanent sterilization is currently Federal Drug
      Administration (FDA) approved. The hysteroscopic approach obviates the need for
      general anesthesia and surgical incision. The device is a dynamically expanding
      micro-insert that, when placed in the proximal portion of the fallopian tube,
      generates a benign tissue response that results in anchoring of the device and
      subsequent occlusion of the tube. The current trial of 745 women seeking birth
      control from Australia, Europe, and the United States were evaluated for
      successful micro-insert placement at three months. Comfort, safety, and return to
      normal activity were evaluated. All patients were followed for five years and
      returned for annual gynecologic status. Procedure time was 18 minutes, 92%
      returned to work in one day. There were no reported pregnancies among these
      patients in 27,526 months. The transcervical approach for sterilization
      represents ease of application, low morbidity, and convenience to the patient.

PMID- 15744683
TI  - Laparoscopic hysterectomy for advanced endometriosis including rectosigmoid
      disease.
AB  - Endometriosis is best treated by surgical excision. This can be accomplished
      either by excision of the endometriosis with reproductive tract preservation or
      by excision of endometriosis with hysterectomy. This latter approach eliminates
      endometriosis in the muscle of the uterus (where it is called adenomyosis) and is
      especially effective for pelvic pain. Ovarian preservation can be considered
      using hysterectomy if the surgeon excises most of the endometriosis. Techniques
      to excise endometriosis, including rectosigmoid disease, and perform hysterectomy
      are detailed in this chapter.

PMID- 15744684
TI  - Pelosi minimally invasive technique of cesarean section.
AB  - In the mid-1990s, the authors introduced a minimally invasive system of cesarean
      delivery. This article illustrates the improvements made since the technique's
      initial publication. The Pelosi Minimalist Cesarean procedure is the simplest and
      least traumatic approach of cesarean delivery. The procedure described herein
      features a short operating time, minimal instrumentation, reduced surgical
      dissection, decreased postoperative pain, and reduced risk of blood loss,
      infection, and wound complications. It is easily learned and cost-effective, with
      a brief postoperative recovery period.

PMID- 15744685
TI  - Lift-laparoscopic total hysterectomy as a routine procedure.
AB  - In this study, laparoscopic hysterectomy was done with a special lift system that
      elevates the abdominal wall without carbon dioxide (CO2) insufflation. During
      this procedure, bipolar diathermy scissors also were used, which disconnected the
      uterus from its vessels and ligaments. The uterus was then removed through the
      vagina. In 403 cases, variables including operation time, complication rate,
      blood loss, postoperative pain, hospital stay, vaginal discharge, and
      convalescence time were examined. Compared with other laparoscopic methods
      [laparoscopic-assisted vaginal hysterectomy (LAVH), supracervical hysterectomy,
      and total laparoscopic hysterectomy], all those examined showed better results.
      Further advantages of the gasless Lift-laparoscopic total hysterectomy are lower
      costs and an effective "learning curve." Use of this method routinely could
      decrease the number of conventional-surgical hysterectomies that result in
      additional complications.

PMID- 15744686
TI  - Pelosi minilaparotomy hysterectomy: a non-endoscopic minimally invasive
      alternative to laparoscopy and laparotomy.
AB  - T he authors' technique of minilaparotomy hysterotomy is a new modality that
      combines the technical benefits of conventional laparotomy with the minimally
      invasive convalescent and cosmetic advantages of laparoscopic surgery. For
      patients in whom vaginal hysterectomy is considered contraindicated, this
      procedure offers an effective and safe minimal access alternative. This
      redesigned minilaparotomy approach relies on traditional open techniques and
      experience instrumentation that avoid the cost of expensive equipment, long
      learning curve, and prolonged operating time associated with laparoscopic
      surgery, as well as the convalescent disadvantages of a standard laparotomy.

PMID- 15744688
TI  - The transobturator sling: newest tension-free suburethral sling for treatment of
      stress urinary incontinence.
AB  - T his innovative sling system places the sling between the obturator foramens
      using a perineal approach while preserving an intact retropubic space. Potential
      complications associated with tension-free sling systems that use needle-carrier
      placement through the retropubic space, such as the tension-free vaginal tape
      (TVT, Gynecare, Ethicon, Somerville, NJ, USA), are eliminated and routine
      cystoscopy is not required. The procedure is effective and safe for the primary
      treatment of stress urinary incontinence in patients with urethral hypermobility,
      intrinsic sphincter deficiency, or both. It is equally efficient in treatment of
      recurrent and mixed urinary incontinence. Short-term results are similar to those
      of the retropubic tension-free slings.

PMID- 15744687
TI  - Laparoscopic-assisted extracorporeal ovarian cystectomy: a new technique.
AB  - An increasing number of adnexal masses are currently managed laparoscopically,
      which has hampered progress regarding the different techniques of laparoscopic
      surgery. In this chapter, a modified application of surgical instrument was
      described in laparoscopic ovarian cystectomy-we named this device, Lap-Disc Mini.
      This new instrument has three rings, an inner flexible ring fixed to a middle
      ring by a rubber corset, and an additional dynamic outer ring that has a rubbery
      like iris opening, which allows the application of different-sized trocars and
      extracorporeal ovarian cystectomy. This technique has proved to be effective and
      safe, especially in removing large ovarian cyst.

PMID- 15744689
TI  - Latest development in split liver transplantation.
AB  - Currently, orthotopic liver transplantation (LT) represents the treatment of
      choice for most end-stage liver diseases. Advances in surgical techniques and
      immunosuppressive therapy have markedly increased its success. However, the main
      obstacle in LT remains the lack of donor organs with a current mortality rate for
      patients on the waiting list of up to 20%. This chapter focuses on developments
      in SLT techniques and living-donor LT to alleviate this problem. SLT yields a net
      gain of organs, in that it uses one organ to save either an adult and a child, or
      two adults. The initially used technique of ex-situ splitting is being replaced
      progressively by the in-situ splitting technique, which yields better preserved
      grafts. The latest step has been the introduction of living-donor segmental LT.
      The systematic combination of both techniques may lead to a further reduction of
      mortality for patients on the waiting list for LT.

PMID- 15744690
TI  - Surgical impact of computerized 3D CT-based visualizations in living donor liver
      transplantation.
AB  - For living donor liver transplantation (LDLT), accurate diagnostic evaluation is
      essential. Problems arise in assessment of the vascular, bile duct anatomy, liver
      graft volume, and vascular territories involved. Requirements for the realization
      of decision-support and enhanced precision in the planning of surgery in LDLT
      engineering fields are a three-dimensional (3D) visualization system that
      improves anatomic assessment, allows for interactive surgery planning, and acts
      as an intraoperative guide. Thirteen LDLT candidates and three LDLT recipients
      were assessed by "multislice" computer-tomographic examinations. Image processing
      for 3D visualization included segmentation and calculation of centre lines. A
      hierarchical mathematical model representing the vascular and biliary tree was
      created, which allowed calculation of individual vascular territories. Precision
      of 3D computed tomography (CT)-based visualizations was superior to diagnostic
      modalities used currently. In addition to detection of decisive anatomic
      variants, computerized interactive insertion of splitting lines allowed for
      better planning of the surgical approach and image-guided surgery. 3D CT-based
      visualization in LDLT facilitates diagnostic evaluation with high accuracy.
      Multiple examinations, especially with regard to invasive diagnostics, may be
      avoided. Surgical strategy was directly influenced by the detection of vascular
      and biliary variants.

PMID- 15744691
TI  - Benefits and complications of total sternotomy and ministernotomy in cardiac
      surgery.
AB  - Ministernotomy (MS) is a well-known procedure developed in the past ten years
      along with the rise of minimally invasive cardiac surgery. Upper, mid, or
      inferior partial sternotomies allow coronary surgery, as well as aortic and
      mitral valve approaches. Contrary to anterior thoracotomy, access to the great
      vessels is sometimes easy, which renders central cannulation possible. In
      opposition to total sternotomy (TS), MS could procure better postoperative
      stability that would aide in reduction of wound infections. Nevertheless, upper
      MS can be responsible for the lesion of the internal thoracic arteries (ITAs).
      Moreover, little evidence exists regarding blood sparing in MS approaches. MS
      presents the problem of hiding a part of the cardiac structures. For example, in
      the case of aortic surgery by way of upper sternotomy for example, left venting
      is risky or even impossible. However, partial inferior sternotomy can be
      interesting for aortic valve surgery in patients with in situ right ITA passing
      in front of the aorta, protecting the grafts during dissection. In coronary
      surgery, inferior T sternotomy and C sternotomy allow perfect access to the
      coronary network. Some authors also have described inferior "T" sternotomy for
      various congenital lesions. If mini-invasive cardiac surgery can offer reduced
      postoperative morbidity and faster rehabilitation, the advantages of MS upon TS-
      except for cosmetic aspects--remain to be defined. Thus, this approach should be
      reserved for selected patients and lesions.

PMID- 15744692
TI  - New trends in non-invasive coronary angiography with multislice CT.
AB  - Recent trends in computed tomography (CT) scanner technology has opened new
      frontiers in the field of non-invasive coronary angiography. Given the relatively
      important number of negative invasive angiographies performed each year,
      eliminating the risks inherent to this procedure by non-invasive methods greatly
      contribute to diminishing the risk. After injection of contrast, the procedure is
      performed under short apnea and triggered by electrocardiographic (ECG) recording
      that provides a multitude of possible image reconstructions; ie, volume
      rendering, virtual angioscopy, and three-dimensional (3D) reconstruction of the
      heart and coronary vessels. In 100 patients, adequate visualisation of the
      coronary arteries was achieved in 98%, with the advantage of visualizing the
      coronary wall as well as the lumen. The main reasons for failure were arrhythmia
      and excessive motion. Besides evaluating coronary artery atherosclerosis,
      computed tomography angiography (CTA) allowed the diagnosis of coronary aneurysm
      and exact localization of postoperative false aneurysm. The main disadvantages of
      the technique are the absence of dynamic films and exposure to radiation. The
      increased accuracy and sensitivity of noninvasive coronary angiography make it an
      excellent diagnostic tool and a probable replacement to invasive procedures. It
      should reduce the morbidity and mortality as well as the cost of conventional
      coronary arteriography. Furthermore, it has the added benefit of offering spacial
      resolution of the examined vessels.

PMID- 15744693
TI  - Role of race and sex in diagnosis and one-year follow up of deep venous
      thrombosis.
AB  - This study examines the role of sex and race in the diagnosis and outcome of deep
      vein thrombosis (DVT). A retrospective study was performed of 632 patients who
      underwent venous duplex ultrasound from August 1998 to July 1999. Comparisons
      were made by Chi-square analysis. Seventy-four percent of the patients were women
      and 79% of the total group was African American. Twenty-two percent (140) of the
      examinations were positive for DVT. Of all studies performed in men, 37% were
      positive for DVT, and of all studies performed in women, 18% were positive for
      DVT (P<0.05). Additionally, African-American women were more likely to be
      positive for DVT than Caucasian women. One-year follow up showed that 42% had
      residual thrombus and, regardless of sex, African-Americans were more likely to
      have persistent thrombus than Caucasians (60% vs. 19%). Findings in this study
      suggest, in our cohort, African American women were diagnosed with DVT twice as
      often as Caucasian women and African Americans were more likely to have a
      persistent DVT as compared to Caucasians.

PMID- 15744694
TI  - Endovascular therapy for aortic disease.
AB  - Minimally invasive repair of thoracic and abdominal aortic aneurysms (AAAs) is
      rapidly becoming a vital tool in the arsenal of the vascular specialist.
      Historically, surgical replacement of the aorta has been the "gold standard" for
      treatment of aortic aneurysms. However, transfemoral placement of an endovascular
      stent graft, first described by Dr. Parodi and colleagues in 1991, marked the
      beginning of a new era in treatment of aortic aneurysms. This approach has
      evolved, allowing success with significantly less morbidity. Over time, if the
      long-term results continue to prove favorable, endovascular stent graft repair of
      aortic aneurysms may become the most effective means to treat this life
      threatening disease.

PMID- 15744695
TI  - Minimally invasive total knee replacement using a mini-mid vastus incision
      technique and results.
AB  - This study was performed to determine whether differences existed between primary
      knee replacement performed through a standard medial parapatellar approach, and
      those performed through a minimally invasive mini-mid vastus approach. It was a
      prospective study compared with a retrospective evaluation of a matched cohort.
      In this study, the Genesis(tm) II and its MIS instrumentation were used. Patients
      with the mini-mid vastus MIS incision (MMV MIS) required less pain medication
      post-operatively, regained their flexion more rapidly, and attained their
      functional milestones at an earlier point than those with the traditional median
      parapatellar long incision. Despite the smaller incision, component placement was
      radiographically excellent in all cases. Optimal performance of the surgery
      required the use of special instrumentation, modified so as to be used in smaller
      incisions.

PMID- 15744696
TI  - Rapid recovery protocol for peri-operative care of total hip and total knee
      arthroplasty patients.
AB  - Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are among the most
      successful procedures performed in terms of quality-of-life years gained. The
      long-term goals of arthroplasty, to relieve pain, increase function, provide
      stability, and obtain durability, are accomplished in the vast majority of cases.
      The short-term goals, however, have become the target of aggressive peri
      operative programs that aim to speed recovery, reduce morbidity and
      complications, and create a program of efficiency while maintaining the highest
      level of patient care. The concept of rapid recovery is built upon the burgeoning
      interest in less-invasive and small-incision surgeries for (THA and TKA).
      However, the incision size does not appear to be the most critical aspect of the
      program. This article outlines the specific elements of the rapid-recovery
      program for lower-extremity arthroplasty patients, including pre-operative
      patient education, peri-operative nutrition, vitamin and herbal medication
      supplementation, preemptive analgesia, and post-operative rehabilitation. A
      holistic peri-operative, rapid-recovery program has lead to a significantly
      decreased hospital length of stay and significantly lower hospital readmission
      rates in patients who undergo primary THAs and TKAs. Combining these results with
      minimally invasive techniques and instrumentation should make recovery even
      faster.

PMID- 15744698
TI  - Pop-top tibial component: elimination of back-side wear with potential
      modularity.
AB  - Survivorship analysis has demonstrated the excellent long-term clinical success
      of total knee arthroplasty (TKA). Despite multiple attempts to enhance fixation
      with cementless technology, cemented TKA continues to be the "gold standard." The
      rate of loosening has diminished as the accuracy of implantation has been
      improved through sophisticated instrumentation and enhanced experience. Current
      technology with respect to computer-assisted surgery serves only to improve the
      accuracy of implantation, leaving materials as the weakest link in the long-term
      survivorship of TKA. Failure secondary to polyethylene wear has ranked as one of
      the most frequent causes for revision. Many issues have been identified as
      contributory to polyethylene wear and include the quality of the polyethylene,
      manufacturing process, nature of the tibial-femoral or patellofemoral
      articulation, area of contact, sterilization process, and issues pertaining to
      modularity and so-called backside wear. Long-term clinical studies have
      documented the success of direct compression-molded monoblock tibial components.
      However, the benefits of modularity are widely recognized and include the ability
      to fine tune soft-tissue balance after implantation of metallic devices. In an
      effort to combine the long-term success of direct compression molded monoblock
      tibial components with the occasional need for modularity, a convertible tibial
      component has been introduced. This device is manufactured as a direct
      compression-molded monoblock tibial component. The surgeon has the ability at the
      time of the surgical intervention, or any subsequent intervention, to convert the
      tibial component into a modular device. Therefore, this device addresses, in the
      majority of cases, the concerns that arise from backside wear.

PMID- 15744697
TI  - Osteogenic protein-1 in treatment of tibial nonunions: current status.
AB  - Between 5% to 10% of tibial fractures progress to nonunion, causing substantial
      disability. Bone autografts, along with internal fixation, are the usual
      treatment for these failures, but the morbidity associated with autogenous
      tissues remains problematic. Bone morphogenetic proteins are currently available
      for clinical use and preclinical models, as well as an increasing number of
      patients treated with these molecules demonstrate their safety and efficacy.
      Osteogenic Protein-1, OP-1, has been evaluated in a randomized, prospective,
      multi-institution study of tibial nonunions. Sixty-one patients with 63 nonunions
      received OP-1 and intramedullary rod fixation, and were compared with 61 patients
      with 61 nonunions treated with fresh autogenous bone graft and the same fixation.
      Clinical outcomes (success in 81% of OP-1 and 85% of autograft-treated patients)
      and radiographic evaluation (healing in 75% of OP-1 and 84% of autograft-treated
      patients) were statistically indistinguishable at 9 months following treatment.
      No OP-1 or graft-related adverse events occurred. More than 20% of the autograft
      group had significant donor-site pain 6 months following surgery. OP-1 is a safe
      and effective alternative to autogenous bone in treatment of tibial nonunions.

PMID- 15744699
TI  - Venous thromboembolism prophylaxis: role of factor xa inhibition by fondaparinux.
AB  - Fondaparinux (Arixtra, GlaxoSmithKline, Philadelphia, PA.) is the first synthetic
      selective factor Xa inhibitor. A worldwide phase III program, that consists of
      four randomized, double-blind trials, in patients who underwent surgery for hip
      fracture, and elective hip replacement and elective major knee surgery was
      conducted to compare the benefit-to-risk ratio of a subcutaneous 2.5 mg once
      daily regimen of fondaparinux starting postoperatively versus enoxaparin in
      preventing venous thromboembolism. The overall incidence of venous
      thromboembolism up to day 11 was reduced from 13.7% in the enoxaparin group, to
      6.8% in the fondaparinux group, with a relative risk reduction of 50.6% in favor
      of fondaparinux (95% confidence interval: 40.9% to 59.1%, p<0.001). The overall
      incidence of clinically relevant bleeding was low and did not differ between the
      two groups. The benefit of fondaparinux was consistent across all types of
      surgery and all subgroups. The further randomized, double-blind PENTHIFRA-PLUS
      trial showed that extending fondaparinux prophylaxis from one to four weeks after
      hip fracture surgery was well tolerated and, compared to one-week fondaparinux,
      dramatically reduced delayed venous thromboembolism events from 35.0% to 1.4%
      (p<0.001). Four-week fondaparinux could become the standard thromboprophylaxis
      after hip fracture surgery. Fondaparinux is the first selective factor Xa
      inhibitor approved for use in thromboprophylaxis after orthopedic surgery.

PMID- 15744700
TI  - Reconstructive surgery for permanent palsy of the median nerve.
AB  - Permanent palsies of the median nerve cause severe impairment of hand functions.
      This chapter reviews both the various surgical methods able to restore functions
      and complex mechanisms necessary for brain adaptation to the new functions of the
      cortical areas. Different methods of reconstructive surgery, according to both
      the severity of palsy and patients' needs, are presented. The contemporary
      restoration of sensory function of the paralysed digits is recommended, as
      sensation is a prerequisite for good motor function. The various mechanisms and
      methods useful to obtain good gliding and strength of the transferred tendons are
      stressed. Reconstructive surgery for permanent palsy of the median nerve can
      supply improved function, provided that all the recommendations for a meticulous
      balance of the number of functions to be restored and available motors to be
      transferred, as well as of their strength and course, are addressed.

PMID- 15744702
TI  - Designing the "search pathway" in the development of a new class of highly
      efficient stereoselective hydrosilylation catalysts.
AB  - The direct coupling of oxazolines and N-heterocyclic carbenes leads to chelating
      C,N ancillary ligands for asymmetric catalysis that combine both an "anchor" unit
      and a stereodirecting element. Reacting various N-substituted imidazoles with 2
      bromo-4(S)-tert-butyl- and 2-bromo-4(S)-isopropyloxazoline gave the imidazolium
      precursors of the stereodirecting ancillary ligands. A library of ten different
      ligand precursors was obtained by using this simple procedure (65-97 % yield).
      These protioligands were metalated in a subsequent step by reaction with [{Rh(mu
      OtBu)(nbd)}2] (nbd=norbornadiene), generated in situ from KOtBu and
      [{RhCl(nbd)}2] giving the corresponding N-heterocyclic carbene complexes
      [RhBr(nbd)(oxazolinyl-carbene)] 4 a-j in good yields. X-ray diffraction studies
      of two of the rhodium complexes, 4 d and 4 j, established a distorted square
      pyramidal coordination geometry with the bromo ligand occupying the apical
      position. The rhodium-carbene bond length was found to be 2.070(4) A (4 d) and
      2.012(3) A (4 j). Complexes 4 a-j were treated with AgBF4 in dichloromethane,
      giving the active cationic square-planar catalysts for the hydrosilylation of
      ketones. As a reference reaction for the catalyst optimisation, the
      hydrosilylation of acetophenone with diphenylsilane was studied and the system
      optimised with respect to the counterion (BF(4) (-)), solvent (THF) and the
      silane reducing agent (diphenylsilane). The reaction product (1-phenylethanol)
      was obtained with the highest enantiomeric excess (ee) by carrying out the
      reaction at -60 degrees C, whilst the enantioselectivity drops upon going both to
      lower and higher temperatures. The observation that the temperature dependence of
      the ee values goes through a maximum indicated a change in the rate-determining
      step as the temperature is varied. The determination of the initial reaction rate
      in the hydrosilylation of acetophenone upon varying the catalyst (4 d) and
      substrate concentrations at -55 degrees C established a rate law for the initial
      conversion which is first-order in both substrates as well as the catalyst (Vi =
      k[4][PhCOMe][Ph2SiH2]). The catalytic system derived from complex 4 d was found
      to afford high yields and good enantioselectivities in the reduction of various
      aryl alkyl ketones (acetophenone: 92 % isolated yield and 90 % ee, 2-naphtyl
      methyl ketone: 99 % yield, 91 % ee). The selectivity for the reduction of
      prochiral dialkyl ketones is comparable or even superior to the best previously
      reported for prochiral nonaromatic ketones; whereas cyclopropyl methyl ketone is
      hydrosilylated with an enantioselectivity of 81 % ee, the increase of the steric
      demand of one of the alkyl groups leads to improved ee's, reaching 95 % ee in the
      case of tert-butyl methyl ketone. Linear chain n-alkyl methyl ketones, which are
      particularly challenging substrates, are reduced in good asymmetric induction,
      such as 2-octanone (79 % ee) and even 2-butanone (65 % ee).

PMID- 15744701
TI  - Evolving transforaminal endoscopic microdecompression for herniated lumbar discs
      and spinal stenosis.
AB  - The objective of this chapter was to demonstrate evolving transforaminal
      endoscopic microdecompression for herniated lumbar discs and spinal stenosis, and
      to become accomplished with endoscopic micro spinal instruments and laser
      application. Since 1993, 2000 patients with 3421 herniated lumbar discs were
      diagnosed with symptomatic lumbar single and multiple herniated intervertebral
      discs. Progressive series of different diameters endoscopic-assisted tubular
      retractors, with appropriate-sized dilators and more aggressive saw-toothed
      trephines, and laser were used to perform transforaminal endoscopic micro
      decompression, in addition to the posterior-lateral foraminoscope and endoscopic
      assisted spinal operating systems. No postoperative mortalities occurred, and the
      morbidity rate was less than 1%, in the 2000 patients. For a single level, 94% of
      the patients had good or excellent results; 6% had some residual symptoms
      although improved overall. Transforaminal endoscopic laser microdecompression can
      effectively decompress herniated lumbar discs and spinal stenosis, when
      foraminoplasty is performed, which provides a safe and effective modality to
      achieve results in effective spinal decompression, preserves spinal motion, and
      creates a channel for spinal arthroplasty.

PMID- 15744704
TI  - Preparative manipulation of gold nanoparticles by reversible binding to a
      polymeric solid support.
AB  - A preparative scheme is presented for controlled modification of gold
      nanoparticles (NPs) by using reversible binding to a polymeric solid support
      through boronic acid chemistry. Octanethiol-capped Au NPs were bound to a boronic
      acid functionalized resin by custom-synthesized bifunctional linker molecules.
      The NPs were chemically released from the resin to the solution, with one (or a
      few) linker molecules embedded in their capping layer. This was confirmed by
      rebinding the linker-derivatized NPs to a boronic resin, exploiting the
      reversibility of the boronic acid/diol chemistry. The same scheme was employed to
      demonstrate a new method for affinity separation of NPs by means of a solid-phase
      reaction. The use of boronic acid provides versatility and chemical
      reversibility, while the polymeric solid support affords the separation and
      preparative aspects. The method presented here may be useful in various facets of
      NP handling, manipulation, and separation.

PMID- 15744703
TI  - Penetrating missile injuries during asymmetric warfare in the 2003 Gulf conflict.
AB  - BACKGROUND: War wounds produce a significant burden on medical facilities in
      wartime. Workload from the recent conflict was documented in order to guide
      future medical needs. METHODS: All data on war injuries were collected
      prospectively. This information was supplemented with a review of all patients
      admitted during the study period. RESULTS: During the first 2 weeks of the
      conflict, the sole British field hospital in the region received 482 casualties.
      One hundred and four were battle injuries of which nine were burns. Seventy-nine
      casualties had their initial surgery performed by British military surgeons and
      form the study group. Twenty-nine casualties (37 per cent) sustained gunshot
      wounds, 49 (62 per cent) suffered wounds from fragmentation weapons and one
      casualty detonated an antipersonnel mine. These 79 patients had a total of 123
      wounds that were scored prospectively using the Red Cross Wound Classification.
      Twenty-seven (34 per cent) of the wounded were non-combatants; eight of these
      were children. Four patients (5 per cent) died. CONCLUSION: War is changing;
      modern conflicts appear likely to be fought in urban or remote environments,
      producing different wounding patterns and placing non-combatants in the line of
      fire. Military medical skills training and available resources must reflect these
      fundamental changes in preparation for future conflicts.

PMID- 15744705
TI  - Sequestered plutonium: [Pu(IV){5LIO(Me-3,2-HOPO)}2]--the first structurally
      characterized plutonium hydroxypyridonate complex.
AB  - The first single-crystal X-ray diffraction analysis of a hydroxypyridonate
      plutonium(IV) complex is presented, that of the tetradentate ligand 5LIO(Me-3,2
      HOPO) with Pu(IV). The [Pu(IV){5LIO(Me-3,2-HOPO)}(2)] complex crystallizes in the
      space group Pna2(1) with the asymmetric unit cell containing two unique eight
      coordinate plutonium complexes and one perchlorate anion. According to shape
      measure analysis, the geometry of both Pu centers is closest to a bicapped
      trigonal prism (C(2v) symmetry, for Pu 1: S(C(2v))=13.48 degrees , S(D(4d))=15.43
      degrees , S(D(4d))=16.10 degrees ). The average bond length for the Pu-
      O(phenolic) is 2.31(4) A, whereas the Pu--O(amide) distances are slightly longer,
      averaging 2.40(2) A. The preparative chemistry of this compound and the
      implications of the structure are discussed.

PMID- 15744706
TI  - Stereoselective synthesis of highly enantioenriched (E)-allylsilanes by palladium
      catalyzed intramolecular bis-silylation: 1,3-chirality transfer and
      enantioenrichment via dimer formation.
AB  - Highly enantioenriched (E)-allylsilanes have been synthesized from optically
      active allylic alcohols on the basis of Pd-catalyzed intramolecular bis
      silylation followed by highly stereospecific Si-O elimination reactions. The
      method involves three steps: 1) O-disilanylation of the allylic alcohols with
      chlorodisilanes, 2) intramolecular bis-silylation in the presence of a 1,1,3,3
      tetramethylbutyl isocyanide/[Pd(acac)2] (acac = acetylacetonate) catalyst at 110
      degrees C, and 3) treatment of the reaction mixture with organolithium reagents.
      The overall transformation proceeds with nearly complete conservation of the
      enantiopurity of the starting allyl alcohols by transposition of the C=C bond.
      For instance, (R)-(E)-3-decen-2-ol (99.6-99.7 % ee) produced (S)-(E)-4
      (organosilyl)-2-decene of 98.8-99.4 % ee for a variety of silyl groups, including
      Me3Si, Me2PhSi, tBuMe2Si, Et3Si, and iPr3Si. In the bis-silylation step, the
      initially formed trans-1,2-oxasiletanes immediately dimerize to stereoselectively
      give 1,5-dioxa-2,6-disilacyclooctanes, which are isolated in high yield by
      carrying out the reaction at 70 degrees C. The eight-membered ring compounds
      undergo thermal extrusion of (E)-allylsilanes in high yield at 110 degrees C,
      along with formation of 1,3-dioxa-2,5-disilacyclohexane derivatives. These in
      turn undergo a Peterson-type elimination by treatment with nucleophiles such as
      BuLi and PhLi to give the (E)-allylsilanes. All of the steps involved in the
      sequence proceed with extremely high stereoselectivity and stereospecificity,
      leading to almost complete 1,3-chirality transfer through the overall
      transformation. The dimerization step, which forms diastereomeric intermediates,
      allows the synthesis of a highly enantioenriched allylsilane (99.4 % ee) from an
      optically active allylic alcohol with lower enantiopurity (79.2 % ee) by
      enrichment of enantiopurity. A general method for the determination of the
      enantiomeric excesses of (E)-allylsilanes is also described in detail.

PMID- 15744707
TI  - Loss of amine from platinum(II) complexes: implications for cisplatin
      inactivation, storage, and resistance.
AB  - Potential consequences of the binding of the anticancer drug cisplatin to various
      biomolecules in the cell have been investigated by using a combined density
      functional theory and continuum dielectric model approach. Since the amine
      ligands remain coordinated at the metal upon formation of the most frequent DNA
      adducts, whereas they were found to be displaced from the metal upon formation of
      drug metabolites, we have analyzed the factors governing amine loss from
      platinum(II) complexes as a possible pathway of cisplatin inactivation. The
      calculations systematically show the effect of 1) the trans ligand, 2) the charge
      of complex, 3) the nucleophile, and 4) the environment on the thermodynamic
      instability and kinetic lability of the platinum-amine bonds. After initial
      binding of cisplatin hydrolysis products to thioethers or thiols, loss of the
      amine trans to this sulfur ligand rather than replacement of the sulfur ligand
      itself by other nucleophiles like guanine-N7 is predicted to be the predominant
      reaction. The results of this study contribute to an understanding of the modes
      of cisplatin inactivation prior to DNA binding, for example, by elevated
      glutathione levels in cisplatin-resistant cancer cells.

PMID- 15744708
TI  - The magnetic behaviour of [NnBu4]4[Ni16Pd16(CO)40]: an even-electron homoleptic
      carbonyl-metal cluster anion displaying a J = 2 ground state.
AB  - The magnetic behaviour of the even-electron [Ni16Pd16(CO)40]4- cluster, in its
      [NnBu4]+ salt, has been investigated by magnetometry and muon spin
      rotation/relaxation (muSR) spectroscopy. The susceptibility measurements show an
      exceptionally high magnetic moment corresponding to a total spin value J=2. This
      suggests a Hund filling of a quadruplet ground state, quite unique in carbonyl
      metal clusters. SQUID magnetometry shows a departure from the Curie-Weiss law,
      for T>150 K, and strong deviation from a Brillouin behaviour of the magnetisation
      curves. muSR spectroscopy in zero applied field shows a temperature independent
      decay of the muon spin polarisation, similar to that of a purely paramagnetic
      system. The observed muon spin repolarisation in a moderate external longitudinal
      field, however, invalidates this simple picture and suggests the presence of a
      local anisotropy field acting on the cluster's magnetic moment. A consistent
      interpretation of magnetometry and muSR results implies the occurrence of an
      additional interaction of the cluster spin with an effective crystalline field.
      The inclusion of this interaction in a model Hamiltonian allows us to
      successfully reproduce both the susceptibility and magnetisation data.

PMID- 15744709
TI  - Purification and determination of inhibitory activity of recombinant soyacystatin
      for surimi application.
AB  - A recombinant soyacystatin (r-soyacystatin) was tested for its inhibitory
      activity against cysteine proteinase of Pacific whiting and its activity was
      compared to that of egg white cystatin. A recombinant soyacystatin expressed in
      Escherichia coli was purified to electrophoretic homogeneity using phenyl
      Sepharose and DEAE-Sepharose. Native egg white cystatin was purified by using
      affinity chromatography on CM-papain-Sepharose generated in our lab. Egg white
      cystatin and soyacystatin were tested for proteinase inhibitory activity against
      commercial papain and also cathepsin L purified from Pacific whiting muscle. The
      r-soyacystatin exhibited papain-like protease inhibition activity comparable to
      that of the egg white cystatin, which could inhibit papain and Pacific whiting
      cathepsin L. The r-soyacystatin subsequently inhibited the autolytic activity of
      Pacific whiting surimi.

PMID- 15744710
TI  - Functional foods: planning and development.
AB  - The discussion on functional foods among scientific communities and EC
      commissions is mainly focused on definitions and on legislative issues related to
      the presence on the market of this kind of products. Although many new products
      continuously appear, the functional food market is characterized by a high rate
      of failure. To realize a successful functional food, experts having different
      background should work together following a detailed workplan. In this paper, the
      problems related to planning and development of functional foods are considered
      using a step-by-step approach. The strategies for invention and development,
      formulation and validation of nutritional claims are regarded also illustrating
      practical examples of functional food development. The concept of food for
      special medical purposes, intended for individuals who are being treated under
      medical supervision, is also introduced.

PMID- 15744711
TI  - The DFG-Senate Commission on Food Safety (SKLM): a profile.

PMID- 15744714
TI  - Structural elucidation and analysis of thermal degradation products of the
      Fusarium mycotoxin nivalenol.
AB  - The major class of mycotoxins produced by Fusarium moulds are trichothecenes, a
      large group of sesquiterpenes sharing the same basic chemical structure, a 12,13
      epoxytrichothec-9-ene ring system. Their toxic effects range from causing
      diarrhoea, vomiting and gastro-intestinal inflammation to noncompetitive
      inhibition of the biosynthesis of proteins in eukaryotic cells. Trichothecenes in
      general are relatively stable compounds, their degradation is observed only at
      high temperatures and prolonged heating time. In order to investigate the
      stability of the trichothecene nivalenol (NIV) under food processing conditions
      such as cooking or baking, we performed model heating experiments and screened
      the residue for degradation products using gas chromatography-mass spectrometry
      (GC-MS). Heating of nivalenol, especially under mild alkaline conditions, gave a
      mixture of four compounds (norNIV A, norNIV B, norNIV C, and NIV lactone), which
      where isolated and identified by nuclear magnetic resonance (NMR) and MS
      experiments. Although their formation was also demonstrated in heating
      experiments with spiked flour samples, only norNIV B was detectable in a
      screening of several commercially available samples, possibly due to the very low
      contamination with nivalenol. Furthermore, cell culture experiments using
      immortalized human kidney epithelial (IHKE) cells showed that the four compounds
      are less cytotoxic (formazan dye cytotoxicity assay) compared to nivalenol.
      Whereas nivalenol revealed an EC50 at 0.9 micromol, all other compounds did not
      show any significant effect up to 100 micromol.

PMID- 15744715
TI  - The health risk of nitrosamines with Gerhard Eisenbrand.

PMID- 15744716
TI  - Quercetin alleviates activities of intestinal and renal disaccharidases in
      streptozotocin-induced diabetic rats.
AB  - Specific activities of both intestinal and renal dissacharidases, such as
      sucrase, maltase, and lactase, were altered in diabetic rats. Our study was
      focused to evaluate the effect of feeding quercetin - a bioflavanoid on
      intestinal and renal dissacharidases in streptozotocin-induced diabetic rats. The
      rats were fed with 0.1% quercetin in diet. A reduction in intestinal maltase and
      sucrase, activities in quercetin-fed diabetic rats was observed in contrast to
      the increased activities in the starch-fed diabetic rats. A significant
      amelioration in renal dissacharidase activities in quercetin-fed diabetic rats
      was observed when compared to decreased activity in starch-fed diabetic rats.

PMID- 15744717
TI  - Patulin reduces glutathione level and enzyme activities in rat liver slices.
AB  - In the present study, an attempt was made to identify glutathione (GSH) adducts
      of patulin in precision-cut rat liver slices, which were used as a model system
      to study the metabolism and biological effects of this mycotoxin. Patulin
      disappeared in the slices but none of the GSH adducts, previously demonstrated in
      the chemical reaction of patulin with GSH, could be detected by HPLC. After
      incubation with various concentrations of patulin, a concentration-dependent
      decline of the GSH level was observed in the slices. For example, only 25% of the
      GSH of controls was found with 200 microM patulin. The activities of glutathione
      S-transferase (GST) and of drug metabolizing phase I and phase II enzymes,
      assayed by the hydroxylation and conjugation of testosterone, were also reduced.
      On the other hand, incubation with patulin markedly increased lipid peroxidation
      in the slices. The effects of patulin on enzyme activities and lipid peroxidation
      may be a consequence of the GSH decline, which cannot be accounted for by a
      direct reaction of patulin with GSH due to the high concentration of GSH in
      hepatocytes. The decrease of GSH level and GST activity may be related to the
      putative mutagenic and carcinogenic potential of patulin.

PMID- 15744718
TI  - Hepatic and intestinal first-pass effects of oltipraz in rats.
AB  - It was reported that the mean value of the extent of absolute oral
      bioavailability (F) of oltipraz at a dose of 20 mg/kg was 41.2% and only 2.68% of
      the oral dose was unabsorbed from the gastrointestinal tract in rats. Hence, the
      low F in rats could be due to considerable first-pass (gastric, intestinal and
      hepatic) effects. Hence, the first-pass effects of oltipraz were measured after
      intravenous, intraportal, intragastric and intraduodenal administration of the
      drug at a dose of 20 mg/kg to rats. The total area under the plasma concentration
      time curve from time zero to time infinity (AUC) values between intragastric and
      intraduodenal administration (213 and 212 microg min/ml) in rats were almost
      similar, but the values were significantly smaller than that after intraportal
      administration (316 microg min/ml) in rats, indicating that gastric first-pass
      effect was almost negligible (due to negligible absorption of oltipraz from rat
      stomach), but the intestinal first-pass effect of oltipraz was considerable,
      approximately 32% of the oral dose. The hepatic first-pass effect of oltipraz was
      approximately 40% based on AUC values between intravenous and intraportal
      administration (319 versus 536 microg min/ml). Since approximately 65% of the
      oral oltipraz was absorbed into the portal vein, the value of 40% was equivalent
      to 25% of the oral dose. The low F of oltipraz in rats was mainly due to
      considerable hepatic and intestinal first-pass effects.

PMID- 15744719
TI  - Corrosion behavior of cast Ti-6Al-4V alloyed with Cu.
AB  - It has recently been found that alloying with copper improved the inherently poor
      grindability and wear resistance of titanium. This study characterized the
      corrosion behavior of cast Ti-6Al-4V alloyed with copper. Alloys (0.9 or 3.5 mass
      % Cu) were cast with the use of a magnesia-based investment in a centrifugal
      casting machine. Three specimen surfaces were tested: ground, sandblasted, and as
      cast. Commercially pure titanium and Ti-6Al-4V served as controls. Open-circuit
      potential measurement, linear polarization, and potentiodynamic cathodic
      polarization were performed in aerated (air + 10% CO(2)) modified Tani-Zucchi
      synthetic saliva at 37 degrees C. Potentiodynamic anodic polarization was
      conducted in the same medium deaerated by N(2) + 10% CO(2). Polarization
      resistance (R(p)), Tafel slopes, and corrosion current density (I(corr)) were
      determined. A passive region occurred for the alloy specimens with ground and
      sandblasted surfaces, as for CP Ti. However, no passivation was observed on the
      as-cast alloys or on CP Ti. There were significant differences among all metals
      tested for R(p) and I(corr) and significantly higher R(p) and lower I(corr)
      values for CP Ti compared to Ti-6Al-4V or the alloys with Cu. Alloying up to 3.5
      mass % Cu to Ti-6Al-4V did not change the corrosion behavior. Specimens with
      ground or sandblasted surfaces were superior to specimens with as-cast surfaces.

PMID- 15744721
TI  - Gracilis muscle flap for aesthetic reconstruction in the head and neck region.
AB  - Microsurgical tissue transfer has constantly improved the therapeutic options for
      reconstruction in the head and neck region, but the ideal flap has yet to be
      found. The purpose of this study is to discuss the aesthetic potential of the
      free gracilis muscle flap in difficult head and neck reconstruction. We report
      our experience with the free gracilis muscle flap in seven patients who underwent
      reconstruction in the head and neck region for a variety of indications. In all
      seven patients, the transplanted muscle flaps healed well, with no flap loss.
      Postoperative complications consisted of skin-graft loss in one patient requiring
      a second split-thickness skin graft. Donor-site morbidity was minimal in all
      patients. For difficult reconstruction in the head and neck region, the free
      gracilis muscle flap offers a number of advantages, including reliable vascular
      anatomy, relatively great plasticity, and a concealed donor area. Thus this type
      of flap offers a valuable option whenever an aesthetically pleasing result is
      sought.

PMID- 15744720
TI  - Angiographic views used for percutaneous coronary interventions: a three
      dimensional analysis of physician-determined vs. computer-generated views.
AB  - The goal of this study was to determine the severity of vessel foreshortening in
      standard angiographic views used during percutaneous coronary intervention (PCI).
      Coronary angiography is limited by its two-dimensional (2D) representation of
      three-dimensional (3D) structures. Vessel foreshortening in angiographic images
      may cause errors in the assessment of lesions or the selection and placement of
      stents. To date, no technique has existed to quantify these 2D limitations or the
      performance of physicians in selecting angiographic views. Stent deployment was
      performed in 156 vessel segments in 149 patients. Using 3D reconstruction models
      of each patient's coronary tree, vessel foreshortening was measured in the actual
      working view used for stent deployment. A computer-generated optimal view was
      then identified for each vessel segment and compared to the working view. Vessel
      foreshortening ranged from 0 to 50% in the 156 working views used for stent
      deployment and varied by coronary artery and by vessel segment within each
      artery. In general, views of the mid circumflex artery were the most
      foreshortened and views of the right coronary artery were the least
      foreshortened. Expert-recommended views frequently resulted in more
      foreshortening than computer-generated optimal views, which had only 0.5% +/-
      1.2% foreshortening with < 2% overlap for the same 156 segments. Optimal views
      differed from the operator-selected working views by > or = 10 degrees in over
      90% of vessels and frequently occurred in entirely different imaging quadrants.
      Vessel foreshortening occurs frequently in standard angiographic projections
      during stent deployment. If unrecognized by the operator, vessel foreshortening
      may result in suboptimal clinical results. Modifications to expert-recommended
      views using 3D reconstruction may improve visualization and the accuracy of stent
      deployment. These results highlight the limitations of 2D angiography and support
      the development of real-time 3D techniques to improve visualization during PCI.

PMID- 15744722
TI  - Salvage operations of free tissue transfer following internal jugular venous
      thrombosis: a review of 4 cases.
AB  - The internal jugular vein (IJV) is used as the optimal recipient for free-tissue
      transfer in reconstruction following modified radical neck dissection. Some
      reports documented rare cases of flap compromise following IJV thrombosis, but
      large sample studies are few. We present cases of emergent exploration and an
      analysis of factors to improve salvage rates of compromise due to IJV thrombosis.
      From a survey of 756 patients, four developed congestion due to IJV thrombosis
      and returned to the operating room. A restrospective analysis was made from the
      case records. This represents a rate of 0.5% for the entire series. Three flaps
      survived,and one failed. Detection of compromise ranged from 7-25 h
      postoperatively. All four IJVs recovered to provide adequate drainage after
      thrombectomy. While flap compromise following IJV thrombosis is rare, careful
      observation and early exploration are crucial for salvage, as in other
      microvascular venous crises.

PMID- 15744723
TI  - Use of varioscope in free microvascular tissue transplants.
AB  - Since July 2002, the author has performed 12 consecutive free flaps using a new
      device, the Varioscope AF3, in order to evaluate its efficacy. The Varioscope is
      a world-patent novelty by Life Optics (Vienna, Austria) that combines the
      philosophy of microscopes and loupes. Specific advantages such as reduced cost,
      freedom of movement, portability, and a magnification range between 3.6-7,2x are
      some of the reasons that convinced the author to use the Varioscope initially.
      The overall success rate is similar to that obtained with a microscope or high
      power loupes. The results show that the Varioscope AF3 could be safely employed
      in the majority of free-tissue transfers as sole means of magnification. However,
      for digital replantations or vessels with a diameter of less than 1 mm, a
      microscope might be necessary.

PMID- 15744724
TI  - Heterotopic cardiac xenotransplantation in rodents: report of a refined technique
      in a hamster-to-rat model.
AB  - Hamster-to-rat heterotopic cardiac xenotransplantation is widely used as an
      experimental model to study xenograft rejection, accommodation, and tolerance, as
      well as in studies aimed at developing immunosuppressive strategies in
      xenotransplantation. Despite its widespread application, no detailed description
      of a surgical technique for this model has been provided in the literature.
      Indeed, all publications so far on the use of this species combination refer to
      the rat allotransplantation technique. Hence the present paper provides a
      detailed, up-to-date description of the surgical method adopted at our center for
      the hamster-to-rat heterotopic cardiac xenotransplantation model. Considerable
      effort went into developing a reliable, reproducible experimental model in
      rodents, and the description given here is enriched with "tips" that we learned
      in the process. The discussion of the technique also addresses several
      significant related issues, e.g., the anesthesia and organ preservation solution
      used (aspects that, in our experience, are crucial to a good surgical outcome).

PMID- 15744725
TI  - Neovascularization in prefabricated flaps using a tissue expander and an
      implanted arteriovenous pedicle.
AB  - Creating prefabricated flaps using tissue expanders in combination with the
      implantation of maximal blood flow vascular pedicles into suitable tissue areas
      represents a new tendency in the reconstruction of large skin defects. In 42
      Chinchilla Bastard female rabbits weighing 3,700-4,600 g, skeletonized
      arteriovenous pedicles with maximal blood flow, dissected from the femoral and
      saphena magna bundles, were implanted underneath abdominal fasciocutaneous flaps.
      Oval tissue expanders of 250 ml were placed and fixed on the abdominal wall to
      expand these prefabricated flaps. The evaluation parameters were macroscopic
      observation, blood analysis, selective microangiography, histology, and
      scintigraphy. The study results showed that neovascularization in expanded
      prefabricated flaps was established from newly formed vessels generated from the
      implanted pedicles and their vascular connections with the originally available
      vasculature in the flap. After 20 days of prefabrication, the entirety of the
      expanded prefabricated flaps was perfused by blood flow supplied from newly
      implanted arteriovenous pedicles. The study indicated that an expanded
      prefabricated flap can be successfully created by the simultaneous implantation
      of a maximal blood flow pedicle in combination with flap expansion.

PMID- 15744726
TI  - Proposed new method for angiographically quantifying neovascularization in
      prefabricated flaps.
AB  - Prefabricated flaps have many potential applications in plastic and
      reconstructive surgery. Despite numerous experimental investigations and clinical
      applications, a standard quantification procedure for analyzing
      neovascularization in prefabricated flaps has not yet been established in the
      literature. In this study, we developed a new method for quantifying
      neovascularization, using a standard integral line plate including 25 evenly
      spaced lines corresponding to a 15-cm flap length, which was subsequently
      analyzed under a 2x magnification loupe. Vessel quantity was determined by
      counting the total number of times that vessels perfused by Micropaque
      intersected the integral lines over the entire surface of the flap. This new
      method was used for quantifying neovascularization in 156 prefabricated flaps,
      and we concluded that this technique is very simple and useful, allowing precise
      determination of the amount of neovascularization in prefabricated flaps on
      angiograms. Based on this principle, the quantification of neovascularization in
      any size of prefabricated flap can be easily performed using suitably modified
      integral line plates corresponding to the various flap dimensions.

PMID- 15744727
TI  - Growth of the pectoral girdle of the Leopard frog, Rana pipiens (Anura: Ranidae).
AB  - This article describes the growth of the anuran pectoral girdle of Rana pipiens
      and compares skeletal development of the shoulder to that of long bones. The
      pectoral girdle chondrifies as two halves, each adjacent to a developing humerus.
      In each, the scapula and coracoid form as single foci of condensed chondrocytes
      that fuse, creating a cartilaginous glenoid bridge articulating with the humerus.
      Based on histological sections, both the dermal clavicle and cleithrum begin to
      ossify at approximately the same time as the periosteum forms around the
      endochondral bones. The dermal and endochondral bones of the girdle form immobile
      joints with neighboring girdle elements; however, the cellular organization and
      growth pattern of the scapula and coracoid closely resemble those of a long bone.
      Similar to a long bone epiphysis, distal margins of both endochondral elements
      have zones of hyaline, stratified, and hypertrophic cartilages. As a result,
      fused elements of the girdle can grow without altering the glenoid articulation
      with the humerus. Comparisons of anuran long bone and pectoral girdle growth
      suggest that different bones can have similar histology and development
      regardless of adult morphology.

PMID- 15744728
TI  - Model of murine interpositional vein grafting.
AB  - A new murine model is presented for interpositional vein grafting into an artery.
      In ICR (outbred) mice, the femoral vein or a branch of the jugular vein was
      harvested and placed into a femoral artery defect, using standard microvascular
      techniques to achieve end-to-end anastomoses with 11-0 nylon suture. The
      technique requires a high level of microsurgical experience and competence.
      Success rates (vessel patency) were higher with moderate systemic heparinization
      (200 units/kg body weight, single i.v. bolus). Vein grafts were successfully
      transplanted between syngenic C57Bl/6J mice, with patency demonstrated from 1 day
      to 3 months postoperatively. The model is applicable to studies of vein graft
      stenosis using murine transgenic/knockout models.

PMID- 15744729
TI  - Gestational exposure to cigarette smoke imperils the long-term physical and
      mental health of offspring.
AB  - BACKGROUND: In this study, we sought to understand whether prenatal exposure to
      cigarette smoke would be associated with increased offspring hospitalization
      through age 22 years for various physical and mental health diagnoses. METHODS:
      We used multivariate logistic regression to investigate the relationship between
      gestational exposure to cigarette smoke and offspring hospitalization for
      physical and mental health conditions based on International Classification of
      Diseases (ICD; World Health Organization) diagnoses. RESULTS: When controlling
      for parental psychiatric status, maternal somatic health, socioeconomic status,
      parity, and maternal age, youth born to mothers who smoked six or more cigarettes
      per day were more likely to have experienced hospitalization for neuroses (OR,
      1.97), diseases of the nervous system (i.e., neurological disorders) (OR, 1.47),
      respiratory infections (OR, 1.28), accidents (OR, 1.44), infections (OR, 1.54),
      undiagnosed symptoms (OR, 1.65), and total admissions (OR, 1.48). Female
      offspring prenatally exposed were more likely to have experienced hospitalization
      for obstetric complications (OR, 2.94). No association was found for the
      remaining categories analyzed: blood disorders, skin diseases, psychoses,
      metabolic/endocrine disease, circulatory disease, digestive disease, disease of
      the skeletal/muscular system, physical anomalies, neoplasms, and genital/urinary
      disease. CONCLUSIONS: This is the first study to investigate the impact of
      gestational exposure to cigarette smoke on global measures of somatic and
      physical health in offspring. This study adds to the literature by demonstrating
      that smoking during pregnancy increases offspring risk for additional health
      outcomes not previously recognized in the literature, and that the effect of
      smoking during pregnancy persists throughout the developmental period. The
      possibility that these findings are related to lifestyle markers or smoke
      exposure during childhood should also be considered.

PMID- 15744730
TI  - Phenytoin teratogenicity: hypoxia marker and effects on embryonic heart rhythm
      suggest an hERG-related mechanism.
AB  - BACKGROUND: The antiepileptic drug phenytoin (PHT) is a human and animal
      teratogen. The teratogenicity has been linked to PHT-induced embryonic cardiac
      arrhythmia and hypoxic damage during a period when regulation of embryonic heart
      rhythm is highly dependent on a specific K(+) ion current (I(Kr)). PHT has been
      shown to inhibit I(Kr). The aims of this study were to investigate whether
      teratogenic doses cause embryonic hypoxia during and after the I(Kr) susceptible
      period and to further characterize PHT effects on embryonic heart rhythm.
      METHODS: Pregnant C57BL mice were administered the hypoxia marker pimonidazole
      followed by PHT or saline (controls) on GD 10 or GD 15. The embryos were fixed
      and sectioned, and the immunostained sections were analyzed with a computer
      assisted image analysis. Effects of PHT (0-250 microM) on heart rhythm in GD 10
      embryos cultured in vitro were videotaped and then analyzed by using a
      digitalization technique. RESULTS: PHT dose-dependently increased the hypoxia
      staining (6- and 11-fold after maternal dosing of 100 and 150 mg/kg,
      respectively) during the period I(Kr) is expressed and functional (GD 10). In
      contrast, there were no differences between the PHT doses in hypoxia staining,
      and much less pronounced hypoxia after this period (GD 15). With increasing PHT
      concentrations, increased length of the interval (bradycardia) and large
      variations in length between individual heartbeats (arrhythmia) were recorded.
      CONCLUSIONS: PHT induced bradycardia/arrhythmia and severe embryonic hypoxia
      during the I(Kr) susceptible period, supporting the idea of an I(Kr)-arrhythmia
      hypoxia-related teratogenic mechanism.

PMID- 15744731
TI  - Behavioral effects of prenatal folate deficiency in mice.
AB  - BACKGROUND: Folate supplementation decreases the incidence of birth defects such
      as neural tube defects (NTDs). We and others have shown that gestational dietary
      folate deficiency that does not produce overt NTDs can alter fetal neural
      histology. Accordingly, murine offspring were examined for the possible
      functional consequences of prenatal folate deficiency. METHODS: CD-1 mice were
      fed a diet of chow containing 400, 600, or 1200 nmol of folic acid/kg of chow for
      eight weeks prior to breeding and until GD18, at which time all dams were placed
      on folate-replete chow. Behavioral tests of male and female offspring included
      righting reflex, negative geotaxis, forelimb hanging, motor coordination, open
      field activity, and elevated plus maze activity. RESULTS: Of greatest
      significance, the adult offspring that were prenatally folate-deficient exhibited
      more anxiety-related behavior in the elevated plus maze. Offspring of the 400
      nmol of folic acid/kg of chow diet group exhibited significantly shorter
      durations in the open arms and longer durations in the closed arms. Further,
      these two behaviors were dose-related. There was also a trend for the prenatally
      folate-deficient adult mice to exhibit more thigmotaxis (wall-hugging) behavior
      in the open field, entering the central area less frequently than controls. There
      were few other differences in tested behaviors between folate-deficient and
      folate-replete mice. CONCLUSIONS: Prenatal folate deficiency that is repleted at
      birth can manifest later with increased anxiety 9-12 weeks after birth.

PMID- 15744732
TI  - Epidemiology of gastroschisis in metropolitan Atlanta, 1968 through 2000.
AB  - BACKGROUND: An increase in the rate of gastroschisis has been documented by birth
      defects surveillance systems in the United States and in other countries. This
      study sought to evaluate historical trends in the rate of gastroschisis in
      Atlanta, Georgia, and to describe the epidemiology of gastroschisis over 33
      years. METHODS: Gastroschisis cases were identified through the Metropolitan
      Atlanta Congenital Defects Program (MACDP) from 1968 through 2000. Poisson
      regression techniques were used to evaluate trends over time. Data on covariates
      were compared for three maternal age groups (< or =19, 20-24, and > or =25
      years). RESULTS: From 1968 through 1975, the rate of gastroschisis was stable at
      0.8 per 10,000 births. After 1975, the rate of gastroschisis was 2.3 per 10,000
      births with no significant increase observed from 1976 through 2000. The rate of
      gastroschisis was six times higher among teenage mothers compared with mothers >
      or =25 years of age. Affected infants born to teenage mothers were less likely to
      be born to Black mothers compared to White mothers (rate ratio [RR], 0.4; 95%
      confidence interval [CI], 0.2-0.6). This was also true for mothers 20-24 years of
      age (RR, 0.5; 95% CI, 0.3-0.8) but not for mothers 25 years of age or older (RR,
      1.6; 95% CI, 0.9-2.7). CONCLUSIONS: An increase in the rate of gastroschisis was
      observed in the mid-1970s, but no temporal trend has been observed since that
      time. In light of recent reports of an increasing prevalence of gastroschisis in
      the United States, continued monitoring of this birth defect is warranted.

PMID- 15744733
TI  - Mouse models of impaired fear memory exhibit deficits in amygdalar LTP.
AB  - Inbred mouse strains have different genetic backgrounds that can result in
      impairments of synaptic plasticity and memory. They are valuable models for
      probing the mechanisms of memory impairments. We examined fear memory in several
      inbred strains, along with synaptic plasticity that may underlie fear memory.
      Long-term potentiation (LTP) is a form of activity-dependent synaptic plasticity
      that is a candidate cellular mechanism for some forms of learning and memory.
      Strains with impaired contextual or cued fear memory may have selective LTP
      deficits in different hippocampal subregions, or in the amygdala. We measured
      fear memory and its extinction in five inbred strains: C57BL/6NCrlBR (B6), A/J,
      BALB/cByJ (BALB), C57BL/10J (B10), and SM/J (SM). We also measured LTP in the
      basolateral amygdala and in the hippocampal Schaeffer collateral-commissural (SC)
      and medial perforant pathways (MPP). All strains exhibited intact contextual fear
      memory 24 h post-training, but cued fear memory was impaired in strains A/J,
      BALB, and SM. At 1 h post-training, both contextual and cued fear memory deficits
      were more widespread: all strains except for B6 and B10 showed impairments of
      both types of memory. Contextual fear extinction was impaired in BALB and SM. We
      found that amygdalar LTP was reduced in strains A/J and BALB, but SC LTP was
      intact in all strains (except for a selective multi-train LTP impairment in
      BALB). MPPLTP was similar in all five strains. Thus, reduced amygdalar LTP is
      correlated with impaired cued fear memory in strains A/J and BALB. Also,
      hippocampal SC LTP is more strongly correlated with 24-h (long-term) than with 1
      h (short-term) contextual fear memory. In this first conjoint study of amygdala
      dependent memory and amygdalar LTP in inbred mice, we identified specific
      hippocampal and amygdalar LTP deficits that correlate with fear memory
      impairments. These deficits should be considered when selecting inbred strains
      for genetic modification.

PMID- 15744734
TI  - Periconceptional dietary intake of myo-inositol and neural tube defects in
      offspring.
AB  - BACKGROUND: Periconceptional intake of nutrients in addition to folic acid may
      contribute to neural tube defect (NTD) etiologies; a likely candidate is myo
      inositol. We investigated whether maternal periconceptional dietary intake of myo
      inositol influenced NTD risk. METHODS: Data were derived from a case-control
      study of fetuses and infants with NTDs among 1989-1991 California births.
      Interviews were conducted with mothers of 454 NTD cases and with mothers of 462
      nonmalformed controls. A standard 100-item food frequency questionnaire was used
      to assess nutrient intake. RESULTS: We observed small increases in risk, with
      increases slightly more evident for anencephaly, associated with intakes of myo
      inositol less than the highest intake quartile, e.g., risk of anencephaly was 1.3
      (0.7-2.4) among fetuses whose mothers consumed lowest versus highest intakes of
      myo-inositol. These small increases, however, were imprecise, and also did not
      indicate increasing risk with decreasing level of myo-inositol intake. Adjusted
      risk estimates did not differ considerably from their unadjusted counterparts.
      CONCLUSIONS: Our results do not indicate that myo-inositol intake, as measured in
      this study, is strongly associated with risk of human NTDs.

PMID- 15744735
TI  - Tetrodotoxin infusions into the dorsal hippocampus block non-locomotor place
      recognition.
AB  - The hippocampus is critical for navigation in an open field. One component of
      this navigation requires the subject to recognize the target place using distal
      cues. The experiments presented in this report tested whether blocking
      hippocampal function would impair open field place recognition. Hungry rats were
      trained to press a lever on a feeder for food. In Experiment 1, they were
      passively transported with the feeder along a circular trajectory. Lever pressing
      was reinforced only if the feeder was passing through a 60 degrees -wide sector.
      Thus, rats preferentially lever pressed in the vicinity of the reward sector
      indicating that they recognized its location. Tetrodotoxin (TTX) infusions aimed
      at the dorsal hippocampi caused rats to substantially increase lever pressing
      with no preference for any region. The aim of Experiment 2 was to determine
      whether the TTX injections caused a loss of place recognition or a general
      increase of lever pressing. A separate group of rats was conditioned in a
      stationary apparatus to press the lever in response to a light. The TTX
      injections did not abolish preferential lever pressing in response to light.
      Lever pressing increased less than half as much as the TTX-induced increase in
      Experiment 1. When these animals with functional hippocampi could not determine
      the rewarded period because the light was always off, lever pressing increased
      much more and was similar to the TTX-induced increase in Experiment 1. We
      conclude that the TTX inactivation of the hippocampi impaired the ability to
      recognize the reward place.

PMID- 15744737
TI  - Is the hippocampal theta rhythm related to cognition in a non-locomotor place
      recognition task?
AB  - The possible correlation of 4-12 Hz hippocampal field oscillations (theta rhythm)
      with motor and cognitive behavior was studied by recording the hippocampal
      electroencephalogram in non-locomoting rats as they solved a hippocampus
      dependent place recognition task. The electroencephalogram (EEG) during the place
      recognition task was compared with the EEG during a control task, which had the
      same motor demands but did not require place recognition. In the place
      recognition task, the rat was passively transported on the periphery of a
      circular rotating arena, operant responses (lever pressing in Experiment 1 and
      licking in Experiment 2) emitted in a 60 degrees reward sector of the arena
      trajectory were reinforced. As expected the theta rhythm was observed during
      "voluntary" movements such as walking and lever pressing. During walking and
      lever pressing, when prominent theta was observed, the frequency increased within
      the first 10 min of a session. When the rats were not moving, during licking or
      staying motionless, both the theta amplitude and frequency were lower compared
      with the EEG during walking. There were no correlations between any theta
      characteristics and cognitive demand of the tasks.

PMID- 15744736
TI  - Impaired remote spatial memory after hippocampal lesions despite extensive
      training beginning early in life.
AB  - Damage to the hippocampus typically produces temporally graded retrograde
      amnesia, whereby memories acquired recently are impaired more than memories
      acquired remotely. This phenomenon has been demonstrated repeatedly in a variety
      of species and tasks, and it has figured prominently in theoretical treatments of
      memory and hippocampal function. A striking exception to the finding of
      temporally graded retrograde amnesia comes from studies with rodents using
      spatial tasks like the water maze. In these studies, recent and remote memory
      were similarly impaired following hippocampal lesions. In contrast to work with
      rodents, studies of patients with medial temporal lobe lesions, including
      complete hippocampal lesions, indicate that remote spatial memory can be intact.
      One difference between studies in humans and studies in rodents is that spatial
      memory in animal studies is acquired during a limited period of time when the
      animals are adults. In contrast, the spatial memory studied in humans was
      acquired beginning at an early age and learning continued for a considerable
      period of time. We initiated training in a standard water maze immediately after
      rats had been weaned at 21 days of age and continued training until the rats were
      young adults (90 days old). Large hippocampal lesions were made 100 days after
      the completion of training. After recovery from surgery, control rats exhibited
      good retention on the first retention probe trial, but rats with hippocampal
      lesions performed at chance. Thus, even after extended training beginning early
      in life, and with a prolonged training-surgery interval, hippocampal lesions
      impair performance in the water maze task. Possible reasons for these findings
      are discussed in the context of the specific performance requirements of the
      water maze task.

PMID- 15744739
TI  - The economic value of informal care: a study of informal caregivers' and
      patients' willingness to pay and willingness to accept for informal care.
AB  - We provide a new test of the feasibility of using contingent valuation to value
      informal care. We start with a theoretical model of informal caregiving and
      derive that willingness to pay depends positively on wealth and negatively on own
      health, whereas the effect of other's health is sign-ambiguous. These predictions
      are tested in two new data sets on patients' and caregivers' willingness to pay
      (WTP) and willingness to accept (WTA) for informal care. The data are generally
      consistent with the theoretical predictions: wealth generally has a positive
      impact and own health a negative impact. Other's health has a mixed effect. We
      find only small differences between WTP and WTA. Our findings suggest that
      contingent valuation may be a useful technique to value informal care in economic
      evaluations of health care.

PMID- 15744738
TI  - Hippocampal neurogenesis is not enhanced by lifelong reduction of glucocorticoid
      levels.
AB  - Neurogenesis of dentate gyrus granule cells is generally considered to be
      negatively regulated by glucocorticoids. We tested the hypothesis that exposure
      to low plasma corticosteroid levels starting in the early postnatal period
      enhances granule cell proliferation rate during adulthood. Rat pups were
      adrenalectomized (ADX) on postnatal day 10 and were then "clamped" throughout
      life at low corticosterone levels via oral supplementation. Neurogenesis was
      determined using BrdU immunochemistry at 3 and 12 months in clamped rats as
      compared with age-matched, sham-operated controls. Rate of neurogenesis did not
      differ between the groups at either 3 or 12 months. It was significantly lower in
      12-month-old compared with 3-month-old rats, despite the presence of an age
      dependent increase of plasma corticosterone only in the sham-ADX rats. Granule
      cell layer volume, granule cell density, and granule cell degeneration
      (determined using apoptotic markers) were indistinguishable in the two groups,
      further supporting the comparable rate of neurogenesis under differing chronic
      glucocorticoid levels. In addition, whereas acute deprivation of plasma
      glucocorticoids (adrenalectomy) in adult rats evoked a burst of granule cell
      neurogenesis, complete elimination of these hormones (by stopping hormone
      supplementation) in adult, early-life ADX/clamped rats did not. These data do not
      support a simple inverse relationship between chronic plasma glucocorticoid
      levels and granule cell neurogenesis. Specifically, chronic modulation of
      glucocorticoid levels commencing early in life evokes additional, adaptive, and
      compensatory mechanisms that contribute to the regulation of granule cell
      proliferation.

PMID- 15744740
TI  - Smart materials as scaffolds for tissue engineering.
AB  - In this review, we focused our attention on the more important natural
      extracellular matrix (ECM) molecules (collagen and fibrin), employed as cellular
      scaffolds for tissue engineering and on a class of semi-synthetic materials made
      from the fusion of specific oligopeptide sequences, showing biological
      activities, with synthetic materials. In particular, these new "intelligent"
      scaffolds may contain oligopeptide cleaving sequences specific for matrix
      metalloproteinases (MMPs), integrin binding domains, growth factors, anti
      thrombin sequences, plasmin degradation sites, and morphogenetic proteins. The
      aim was to confer to these new "intelligent" semi-synthetic biomaterials, the
      advantages offered by both the synthetic materials (processability, mechanical
      strength) and by the natural materials (specific cell recognition, cellular
      invasion, and the ability to supply differentiation/proliferation signals). Due
      to their characteristics, these semi-synthetic biomaterials represent a new and
      versatile class of biomimetic hybrid materials that hold clinical promise in
      serving as implants to promote wound healing and tissue regeneration.

PMID- 15744741
TI  - HPRT mutations, TCR gene rearrangements, and HTLV-1 integration sites define in
      vivo T-cell clonal lineages.
AB  - HPRT mutations in vivo in human T-lymphocytes are useful probes for mechanistic
      investigations. Molecular analyses of isolated mutants reveal their underlying
      mutational changes as well as the T-cell receptor (TCR) gene rearrangements
      present in the cells in question. The latter provide temporal reference points
      for other perturbations in the in vivo clones as well as evidence of clonal
      relationships among mutant isolates. Immunological studies and investigations of
      genomic instability have benefited from such analyses. A method is presented
      describing a T-cell lineage analysis in a patient with HTLV-1 infection. Lineage
      reconstruction of an in vivo proliferating HPRT mutant clone allows timing of the
      integration event to a postthymic differentiated cell prior to the occurrence of
      HPRT mutations.

PMID- 15744742
TI  - Role of infectious diseases in human carcinogenesis.
AB  - The burden of human infectious diseases remains a public health problem
      worldwide. At least 2 billion people are affected by viral infections, and a
      similar number by bacteria or helminths. The long-term effects of these maladies
      have raised particular concern since some infectious agents have been associated
      with chronic human diseases, especially cancer. It is estimated that 13-20% of
      the world cancer cases are associated with some virus, bacteria, or helminth,
      e.g., human papillomavirus, Helicobacter pylori, and Schistosoma haematobium that
      cause cervical, stomach, and urinary bladder cancer, respectively. Certain
      associations between infection and malignancy are strong and irrefutable; others
      are still speculative. This article reviews the infectious agents that have been
      associated with cancer and current knowledge about the mechanisms underlying
      these associations.

PMID- 15744744
TI  - Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a prevalent cause of blindness caused by a large
      number of different mutations in many different genes. The mutations result in
      rod photoreceptor cell death, but it is unknown why cones die. In this study, we
      tested the hypothesis that cones die from oxidative damage by performing
      immunohistochemical staining for biomarkers of oxidative damage in a transgenic
      pig model of RP. The presence of acrolein- and 4-hydroxynonenal-adducts on
      proteins is a specific indicator that lipid peroxidation has occurred, and there
      was strong immunofluorescent staining for both in cone inner segments (IS) of two
      10-month-old transgenic pigs in which almost all rods had died, compared to faint
      staining in two 10-month-old control pig retinas. In 22- and 24-month-old
      transgenic pigs in which all rods and many cones had died, staining was strong in
      cone axons and some cell bodies as well as IS indicating progression in oxidative
      damage between 10 and 22 months. Biomarkers for oxidative damage to proteins and
      DNA also showed progressive oxidative damage to those macromolecules in cones
      during the course of RP. These data support the hypothesis that the death of rods
      results in decreased oxygen consumption and hyperoxia in the outer retina
      resulting in gradual cone cell death from oxidative damage. This hypothesis has
      important therapeutic implications and deserves rapid evaluation.

PMID- 15744745
TI  - Three-dimensional culture of melanoma cells profoundly affects gene expression
      profile: a high density oligonucleotide array study.
AB  - Growth in three-dimensional (3D) architectures has been suggested to play an
      important role in tumor expansion and in the resistance of cancers to treatment
      with drugs or cytokines or irradiation. To obtain an insight into underlying
      molecular mechanisms, we addressed gene expression profiles of NA8 melanoma cells
      cultured in bidimensional monolayers (2D) or in 3D multicellular tumor spheroids
      (MCTS). MCTS containing 10-30,000 cells were generated upon overnight culture in
      poly-Hydroxyethylmethacrylate (polyHEMA) coated plates. Kinetics of cell
      proliferation in MCTS was significantly slower than in monolayer cultures.
      Following long-term culture (>10 days), however, MCTS showed highly compact and
      organised cell growth in outer layers, with necrotic cores. Oligonucleotide
      microarray analysis of the expression of over 20,000 genes was performed on cells
      cultured in standard 2D, in the presence of collagen as model of extracellular
      matrix (ECM), or in MCTS. Gene expression profiles of cells cultured in 2D in the
      presence or absence of ECM were highly similar, with >/=threefold differences
      limited to five genes. In contrast, culture in MCTS resulted in the significant,
      >/=threefold, upregulation of the expression of >100 transcripts while 73 were
      >/=threefold downregulated. In particular, genes encoding CXCL1, 2, and 3 (GRO
      alpha, -beta, and gamma), IL-8, CCL20 (MIP-3alpha), and Angiopoietin-like 4 were
      significantly upregulated, whereas basic FGF and CD49d encoding genes were
      significantly downregulated. Oligonucleotide chip data were validated at the gene
      and protein level by quantitative real-time PCR, ELISA, and cell surface staining
      assays. Taken together, our data indicate that structural modifications of the
      architecture of tumor cell cultures result in a significant upregulation of the
      expression of a number of genes previously shown to play a role in melanoma
      progression and metastatic process.

PMID- 15744743
TI  - N-methyl-D-aspartate and TrkB receptors protect neurons against glutamate
      excitotoxicity through an extracellular signal-regulated kinase pathway.
AB  - N-Methyl-D-aspartate (NMDA) at a subtoxic concentration (100 microM) promotes
      neuronal survival against glutamate-mediated excitotoxicity via a brain-derived
      neurotrophic factor (BDNF) autocrine loop in cultured cerebellar granule cells.
      The signal transduction mechanism(s) underlying NMDA neuroprotection, however,
      remains elusive. The mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol-3 kinase (PI3-K) pathways alter gene expression and are
      involved in synaptic plasticity and neuronal survival. This study tested whether
      neuroprotective activation of NMDA receptors, together with TrkB receptors,
      coactivated the MAPK or PI3-K pathways to protect rat cerebellar neurons. NMDA
      receptor activation caused a concentration- and time-dependent activation of MAPK
      lasting 24 hr. This activation was blocked by the NMDA receptor antagonist MK-801
      but was attenuated only partially by the tyrosine kinase inhibitor k252a,
      suggesting that activation of both NMDA and TrkB receptors are required for
      maximal neuroprotection. The MAPK kinase (MEK) inhibitor U0126 (10 microM)
      partially blocked NMDA neuroprotection, whereas LY294002, a selective inhibitor
      of the PI3-K pathway, did not affect the neuroprotective activity of NMDA.
      Glutamate excitotoxicity decreased bcl-2, bcl-X(L), and bax mRNA levels,. NMDA
      increases Bcl-2 and Bcl-X(L) protein levels and decreases Bax protein levels.
      NMDA and TrkB receptor activation thus converge on the extracellular signal
      regulated kinase (ERK) 1/2 signaling pathway to protect neurons against glutamate
      mediated excitotoxicity. By increasing antiapoptotic proteins of the Bcl-2
      family, NMDA receptor activation may also promote neuronal survival by preventing
      apoptosis.

PMID- 15744747
TI  - Effects of development and iron status on ceruloplasmin expression in rat brain.
AB  - The increased iron content in the brain of subjects with aceruloplasminemia has
      implicated ceruloplasmin (CP) as a major factor in the regulation of regional
      brain iron content. In this study, we investigated the effects of age and iron on
      CP expression in rat brain. In all four regions, the iron concentrations
      increased with developmental age. There is a similar trend in age-induced changes
      in CP mRNA and protein. The CP mRNA and protein levels were both lowest at
      postnatal day (PND) 7. The expression increased gradually with age, reaching the
      highest at PND196 in the striatum and substantia nigra, and at PND21 and PND63 in
      the cortex and hippocampus, respectively. This suggests the existence of an age
      dependent pre-transcriptional regulation and a regionally specific effect of age
      on CP expression in the brain. Although total iron in all four regions was
      significantly lower in the rats fed with a low-iron diet for 6 weeks and higher
      in the rats with a high-iron diet than those in the control animals, no
      significant between-group differences in CP mRNA and protein were found in these
      animals, except in the substantia nigra where a significant increase in CP
      protein in high-iron rats was observed, and the reverse in low-iron rats. These
      findings suggested that the effects of iron on CP expression in the brain may be
      region-specific, and that regulation of CP expression by iron in the substantia
      nigra was at the post-transcriptional level.

PMID- 15744746
TI  - Use of tamoxifen in advanced-stage hepatocellular carcinoma. A systematic review.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of
      cancer mortality worldwide. Survival is poor for patients with advanced-stage
      HCC, and small trials of tamoxifen for patients with this disease have shown
      conflicting results. The authors conducted a systematic review of randomized
      clinical trials to compare the effect of a tamoxifen-containing arm with a
      nontamoxifen-containing arm in advanced HCC. METHODS: Eligible trials were
      identified from the Cochrane Hepato-Biliary Group register and other databases.
      Studies were selected for inclusion and their methodologic quality assessed by
      three independent reviewers. Hazard ratios (HR) were derived for overall survival
      where possible. Metaanalysis was performed using a fixed-effect model. RESULTS:
      The authors identified 10 randomized trials with a total of 1709 patients. Use of
      tamoxifen had no effect on median survival (HR, 1.05; 95% confidence interval,
      0.94-1.16; P = 0.4) or tumor response rate. The findings were stable in
      sensitivity analyses and were not affected by publication bias or inclusion of
      low-quality studies or studies reported in abstract form only. Few adverse events
      or withdrawals were noted. CONCLUSIONS: There was no support for the therapeutic
      use of tamoxifen in advanced HCC, nor for its use as a control arm in future
      clinical trials.

PMID- 15744748
TI  - The impact of HMO penetration on the relationship between nurse staffing and
      quality.
AB  - While there are a number of studies examining the relationship between nurse
      staffing and quality, none has examined structural differences in the
      relationship between nurse staffing and quality contingent upon the level of
      managed care penetration. We used administrative data, and a dynamic panel data
      model to examine this relationship in a panel of 422 acute care hospitals from
      1990 to 1995. We found that there were significant differences in the
      relationship between nurse staffing and both mortality and length of stay
      depending upon the level of HMO penetration in the hospital's market.

PMID- 15744749
TI  - Activation of MAP kinase by muscarinic cholinergic receptors induces cell
      proliferation and protein synthesis in human breast cancer cells.
AB  - Carbachol (Cch), a muscarinic acetylcholine receptor (mAChR) agonist, increases
      intracellular-free Ca(2+) mobilization and induces mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation in MCF-7
      human breast cancer cells. Pretreatment of cells with the selective phospholipase
      C (PLC) inhibitor U73122, or incubation of cells in a Ca(2+)-free medium did not
      alter Cch-stimulated MAPK/ERK phosphorylation. Phosphorylation of MAPK/ERK was
      mimicked by phorbol 12-myristate acetate (PMA), an activator of protein kinase C
      (PKC), but Cch-evoked MAPK/ERK activation was unaffected by down-regulation of
      PKC or by pretreatment of cells with GF109203X, a PKC inhibitor. However, Cch
      stimulated MAPK/ERK phosphorylation was completely blocked by myristoylated PKC
      zeta pseudosubstrate, a specific inhibitor of PKC-zeta, and high doses of
      staurosporine. Pretreatment of human breast cancer cells with wortmannin or
      LY294002, selective inhibitors of phosphoinositide 3-kinase (PI3K), diminished
      Cch-mediated MAPK/ERK phosphorylation. Similar results were observed when MCF-7
      cells were pretreated with genistein, a non-selective inhibitor of tyrosine
      kinases, or with the specific Src tyrosine kinase inhibitor PP2. Moreover, in MCF
      7 human breast cancer cells mAChR stimulation induced an increase of protein
      synthesis and cell proliferation, and these effects were prevented by PD098059, a
      specific inhibitor of the mitogen activated kinase kinase. In conclusion,
      analyses of mAChR downstream effectors reveal that PKC-zeta, PI3K, and Src family
      of tyrosine kinases, but not intracellular-free Ca(2+) mobilization or
      conventional and novel PKC activation, are key molecules in the signal cascade
      leading to MAPK/ERK activation. In addition, MAPK/ERK are involved in the
      regulation of growth and proliferation of MCF-7 human breast cancer cells.

PMID- 15744750
TI  - The gap effect: discontinuities of preferences around dead.
AB  - BACKGROUND: The assessment of health states considered to be worse than dead is a
      controversial issue. OBJECTIVE: To investigate how health states are valued when
      they are close to dead. Differences between adjacent states are compared with the
      differences between the first positive/first negative state with death. METHODS:
      A secondary analysis of the EuroQol EQ-5D data of the measurement of valuation
      and health (MVH) study was made. Visual analog scale (VAS) and time trade-off
      (TTO) preferences for 43 health states were obtained. Various subsets of 13
      states were valued by 3395 respondents. States were rank ordered by their VAS and
      TTO values. Differences between adjacent states were calculated for the VAS and
      the positive and negative TTO values. RESULTS: Complete data were obtained in
      2997 respondents. The differences between the ordered VAS values were equally
      large. In contrast, significant gaps around dead were found for the positive as
      well as the negative TTO values. DISCUSSION: These results are interpreted in
      light of a descriptive QALY model. This model was expanded to include utilities
      worse than dead. The VAS task does not pick up that bad states become
      intolerable, i.e. worse than dead, when they last too long, but the TTO task
      does. The current QALY model seems to lack descriptive validity for states valued
      worse than dead and for states with a maimal endurable time.

PMID- 15744751
TI  - Stem cells and pulmonary metamorphosis: new concepts in repair and regeneration.
AB  - Adult stem cells are likely to have much more versatile differentiation
      capabilities than once believed. Numerous studies have appeared over the past
      decade demonstrating the ability of adult stem cells to differentiate into a
      variety of cells from non-hematopoietic organs, including the lung. The goal of
      this review is to provide an overview of the growth factors which are thought to
      be involved in lung development and disease, describe the cells within the lung
      that are believed to replace cells that have been injured, review the studies
      that have demonstrated the transformation of bone marrow-derived stem cells into
      lung cells, and describe potential clinical applications with respect to human
      pulmonary disease.

PMID- 15744752
TI  - Bone and cartilage formation by skeletal muscle derived cells.
AB  - In adult individuals when most tissues have progressively lost the ability to
      regenerate, bone maintains the potential for a continuous self remodeling. The
      bone marrow has been so far the main recognized source of osteoprogenitor cells
      that contribute to the turnover of the skeletal scaffold. The possibility though
      exists that a pool of osteoprogenitor cells resides within other adult tissues
      and in particular, as reported previously, in other connective tissues such as
      fat and skeletal muscle. In an attempt to identify an alternative source of
      osteoprogenitor cells other than bone marrow we looked into the skeletal muscle.
      A plastic adhering cell population, from now on referred to as skeletal muscle
      derived cells (SMDCs), was obtained from biopsies of human skeletal muscle. SMDCs
      were clonogenic and displayed a fibroblast-like morphology. The isolated cell
      population had a mesenchymal origin as indicated by abundant expression of type I
      collagen, fibronectin, and vimentin and appeared heterogeneous. SMDCs were
      positive for alpha smooth actin, and to a lesser extent for desmin and alpha
      sarcomeric myosin, two specific markers of the myogenic phenotype. Surprisingly
      though SMDCs expressed early markers of an osteogenic commitment as indicated by
      positive staining for alkaline phosphatase, osteopontin, and osteonectin. Under
      the appropriate stimuli, these cells deposited in vitro a mineralized bone matrix
      and a proteoglycan rich matrix. In addition, SMDCs cultured in the presence of
      low serum and insulin differentiated towards adipocytes developing abundant lipid
      droplets in the cytoplasm. Furthermore SMDCs formed three-dimensional bone tissue
      in vivo when implanted in an immunodeficient mouse, and a mature cartilage
      rudiment when maintained as a pellet culture. In summary, we report the isolation
      and characterization of a cell population from the human skeletal muscle not only
      able to express in vitro specific markers of distinct mesenchymal lineages
      (adipogenic, chondrogenic, and osteogenic), but most importantly, able to
      complete the differentiation pathway leading to the formation of bone and
      cartilage. In this respect SMDCs resemble bone marrow stromal cells (BMSCs).

PMID- 15744753
TI  - Identification of in vivo P-glycoprotein mRNA decay intermediates in normal liver
      but not in liver tumors.
AB  - Post-transcriptional regulation at the level of mRNA stability is one important
      mechanism for over-expression of P-glycoprotein (Pgp) genes observed in cultured
      cells and in animals. A previous study has shown that mRNA half-lives for Pgp
      genes in normal liver were less than 2 h, in contrast to greater than 12 h
      measured in a transplantable liver tumor line. This lower turnover rate of Pgp
      mRNA may, in large part, contribute to the abundance of Pgp mRNA in liver tumors.
      The current study sought to investigate the underlying mechanism for the lower
      turnover rate of Pgp2 mRNA previously determined in liver tumors. As a first
      approach, we set out to understand the Pgp2 mRNA decay in both normal liver and
      liver tumors by first identifying and characterizing Pgp2 mRNA degradation
      intermediates. In this study, we showed that the sensitive ligation-mediated
      polymerase chain reaction (LM-PCR) method can be used to detect a homogenous pool
      of in vitro transcribed RNA down to 0.4 ng. By employing gene-specific primers in
      the LM-PCR method, we successfully identified four Pgp2 mRNA decay intermediates
      in normal liver. All four decay intermediates detected correspond to the 5'
      coding region of Pgp2 mRNA, and surprisingly no decay intermediates which
      correspond to 3' untranslated region, 3' coding region or middle coding region
      were found using LM-PCR. The identified decay intermediates are unique to the
      normal liver as they were absent or present at very low level in all three liver
      tumor samples analyzed. This observation supports our previous findings that the
      Pgp mRNA turnover rate is lower in liver tumors than in normal liver. These
      findings have implications for our understanding of the regulation of Pgp mRNA
      turnover in normal and malignant tissues.

PMID- 15744754
TI  - Amelogenin sequence and enamel biomineralization in Rana pipiens.
AB  - The amelogenin gene contributes the majority of tooth enamel proteins and plays a
      significant role in enamel biomineralization. While several mammalian and
      reptilian amelogenins have been cloned and sequenced, basal vertebrate amelogenin
      evolution remains to be understood. In order to start elucidating the structure
      and function of amelogenins in the evolution of enamel, the leopard frog (Rana
      pipiens) was used as a model. Tissues from Rana pipiens teeth were analyzed for
      enamel structure and RNA extracts were processed for sequence analysis. Electron
      microscopy revealed that Rana pipiens enamel contains long and parallel crystals
      similar to mammalian enamel, while immunoreactions confirmed the site-specific
      localization of cross-reactive amelogenins in Rana pipiens enamel. Sequencing of
      amelogenin PCR products revealed a 782bp cDNA with a 546-nucleotide coding
      sequence encoding 181 amino acids. The homology of the newly discovered Rana
      pipiens amelogenin nucleotide and amino acid sequence with the published mouse
      amelogenin was 38.6% and 45%, respectively. These findings report the first
      complete amelogenin cDNA sequence in amphibians and indicate a close homology
      between mammalian enamel formation and Rana pipiens enamel biomineralization.

PMID- 15744755
TI  - Pro-inflammatory effects of Dunkerque city air pollution particulate matter 2.5
      in human epithelial lung cells (L132) in culture.
AB  - Exposure to urban airborne particulate matter (PM) has been associated with
      adverse health effects. The majority of research articles published on air
      pollution PM relate to PM10. However, increasing emphasis and stringent
      regulations have been placed on PM2.5. The mechanisms for PM-induced adverse
      health effects are not well understood, but inflammation seems to be of
      importance. We focused our attention also on the capacity of air pollution PM2.5
      to induce cytotoxic and inflammatory responses in human epithelial lung cells
      (L132) in culture. Particulate matter was collected in Dunkerque, a French
      seaside city characterized by the proximity of industrial activity and heavy
      motor vehicle traffic. Size distribution results showed that the cumulative
      frequency of PM2.5 was 92.15% and their specific surface area was 1 m2 g(-1).
      Inorganic and organic chemicals usually associated with the natural environment
      but also so-called anthropogenic elements were found in PM, suggesting that much
      of the PM was derived from wind-borne dust from the industrial complex and the
      heavy diesel motor vehicle. We observed PM concentration-dependent cytotoxic
      effects in L132 cells (LC10 = 18.84 microg PM ml(-1); LC50 = 75.36 microg PM ml(
      1)). We showed that exposure to Dunkerque City's PM2.5 induced significant
      increases (in a concentration- and time-dependent manner) in protein secretion
      and/or gene expression of inflammatory cytokines (i.e. TNF-alpha, IL-1beta, IL-8,
      GM-CSF, IL-6, TGF-beta1). We hypothesized also that the occurrence of the acute
      inflammatory response might rely on the capacity of such air pollutants to
      generate oxidative species, which have been implicated in the stringent
      regulation of the cytokine network. Hence, we suggest that the development of
      inflammatory effects that worsen over time stems from the cytotoxicity in
      Dunkerque City's PM2.5-exposed L132 cells in culture.

PMID- 15744756
TI  - D-aspartate modulates transcriptional activity in Harderian gland of frog, Rana
      esculenta: Morphological and molecular evidence.
AB  - In the green frog, Rana esculenta, a substantial amount of D-aspartate (D-Asp) is
      found endogenously within the Harderian gland (HG) following its synthesis from L
      aspartate (L-Asp) by an aspartate racemase. The frog HG is an orbital seromucoid
      gland that displays seasonal changes in secretory activity. Our in vivo
      experiments, consisting of i.p. injection of 2.0 mumol/g b.w. D-Asp in frogs
      collected during two periods of differing glandular activity (high or medium-low
      secretory activity), revealed that HG can to take up and accumulate D-Asp and
      that this amino acid may modulate the exocrine secretion through a kinase
      pathway. At a time when the gland shows relatively low secretory activity, i.p.
      administration of D-Asp rapidly induced activation of ERK1 and an increase in
      cells active in RNA synthesis. This increase in transcriptional activity was
      followed by a significant increase in mucous secretion. By contrast,
      administration of exogenous D-Asp when HG was showing high activity rapidly
      induced inhibition of both ERK1 and transcriptional activity. Since D-Asp is
      known to be recognized by receptors for N-methyl-D-aspartic acid (NMDA), it is
      possible that in the HG, D-Asp mediated NMDA activation may enhance the kinase
      pathway. The above activation of opposing stimulatory and inhibitory processes
      could reflect different levels of NMDA-receptor activity, which could vary as a
      function of the level of gland activity. This study provides the first evidence
      of a role for this excitatory amino acid in exocrine secretion. The effects of D
      Asp in HG appear to be specific since they were not seen in frogs treated with
      other D- or L-amino acids with known excitatory effects on neurosecretion.

PMID- 15744757
TI  - Legal issues of addiction assessment: the experience with hair testing in Greece.
AB  - The purpose of this paper is to present Greek law and legislation for crimes and
      felonies regarding drugs of abuse and the interpretation of hair testing results
      with respect to Greek law. Details (such as the process, the decision and the
      competence of the Court, the police record, the indictment, the expert reports,
      the defendant's individuality, the crimes and the penal confrontal and many
      others) from legal cases related to toxicomany and its judicial verification were
      collected and analysed. Laboratory data of cases concerning the laboratory
      evaluation of toxicomany in addicts and also occasionally the legal course of
      cases with addict defendants are presented. In four representative cases
      segmental hair analysis proved that, for as long as the individuals were
      imprisoned, findings with drug substances corresponding to that period were
      lesser or practically absent compared with samples corresponding to the time out
      of prison, which showed increased drug abuse. Hair analysis provides information
      on chronic exposure rather than acute poisoning. Its detection window varies from
      some days to months or even years. The procedure that the law lays down in many
      cases is insufficient and in most cases impossible to abide by. When the medical
      examiner is not able to decide if the claim of toxicomany is real, segmental hair
      analysis may be the only way to prove it. In other cases where the medical
      examiner is able to diagnose the addiction, a segmental hair analysis is
      necessary because it can show long-term drug abuse.

PMID- 15744758
TI  - Effect of beta-naphthoflavone and phenobarbital on the nephrotoxicity of
      chlorotrifluoroethylene and 1,1-dichloro-2,2-difluoroethylene in the rat.
AB  - The role of cytochrome P450 activity in the nephrotoxicity of
      chlorotrifluoroethylene (CTFE) and 1,1-dichloro-2,2-difluoroethylene (DCDFE) was
      investigated in the male rat. Hepatic cytochrome P450 1A1 and principally P450
      2B1/2 were induced by beta-naphthoflavone and phenobarbital, respectively.
      Nephrotoxicity was evaluated by investigating urine biochemical parameters,
      kidney histochemistry and histopathological modifications. Both CTFE and DCDFE
      induce severe nephrotoxicity in rats after 4 h of exposure to 200 and 100 ppm,
      respectively. Compared with controls, activity levels of gamma
      glutamyltranspeptidase (gamma GT), aspartate aminotransferase (AST), alkaline
      phosphatase (ALP) and N-acetyl-beta-D-glucosaminidase (NAG) in 24-h urine were
      increased similarly, but urinary excretion of glucose, proteins and beta2
      microglobulin (beta2-m) and serum urea and creatinine levels were increased.
      Histopathological and histochemical examinations of kidney sections of CTFE- and
      DCDFE-exposed rats revealed cellular necrosis and tubular lesions 24 h after
      exposure. Beta-naphthoflavone-pretreated rats were afforded some protection
      against the nephrotoxicity of CTFE and DCDFE. Phenobarbital did not modify DCDFE
      nephrotoxicity but afforded some protection against CTFE nephrotoxicity. In
      conclusion, CTFE and DCDFE are strong nephrotoxins. Cytochrome P450 1A1 is
      implicated in CTFE and DCDFE metabolism and one or several cytochromes induced by
      phenobarbital are implicated in CTFE metabolism. The P450 cytochromes involved in
      CTFE and DCDFE metabolism probably constitute detoxication metabolic pathways.
      The nephrotoxicity of CTFE and DCDFE is therefore subordinated to the cytochrome
      P450 activity involved in their metabolism.

PMID- 15744759
TI  - Novel approach for classifying chemicals according to skin sensitizing potency by
      non-radioisotopic modification of the local lymph node assay.
AB  - The murine local lymph node assay (LLNA) is currently recognized as a stand-alone
      sensitization test for determining the sensitizing potential of chemicals, and it
      has the advantage of yielding a quantitative endpoint that can be used to predict
      the sensitization potency of chemicals. The EC3 has been proposed as a parameter
      for classifying chemicals according to the sensitization potency. We previously
      developed a non-radioisotopic endpoint for the LLNA based on 5-bromo-2'
      deoxyuridine (BrdU) incorporation (non-RI LLNA), and we are proposing a new
      procedure to predict the sensitization potency of chemicals based on comparisons
      with known human contact allergens. Nine chemicals (i.e. diphencyclopropenone, p
      phenylenediamine, glutaraldehyde, cinnamicaldehyde, citral, eugenol, isopropyl
      myristate, propyleneglycol and hexane) categorized as human contact allergen
      classes 1-5 were tested by the non-RI LLNA with the following reference
      allergens: 2,4-dinitrochlorobenzene (DNCB) as a class 1 human contact allergen,
      isoeugenol as a class 2 human contact allergen and alpha-hexylcinnamic aldehyde
      (HCA) as a class 3 human contact allergen. Consequently, nine test chemicals were
      almost assigned to their correct allergen class. The results suggested that the
      new procedure for non-RI LLNA can provide correct sensitization potency data.
      Sensitization potency data are useful for evaluating the sensitization risk to
      humans of exposure to new chemical products. Accordingly, this approach would be
      an effective modification of LLNA with regard to its experimental design.
      Moreover, this procedure can be applied also to the standard LLNA with
      radioisotopes and to other modifications of the LLNA.

PMID- 15744760
TI  - Lead-induced changes in human erythrocytes and lymphocytes.
AB  - In the present work we studied, by chemiluminescence measurements, the influence
      of lead on the production of reactive oxygen species (ROS) in haemolysates
      obtained from human erythrocytes incubated in the presence of different
      concentrations of lead acetate. Moreover, we evaluated the modification of
      proteins and lipids in human erythrocyte and lymphocyte membranes by using the
      fluorescence probes N-(1-pyrene)maleimide (PM), laurdan and pyrene. No
      significant changes in chemiluminescence were detected for erythrocytes incubated
      with 1-10 microM lead acetate for 3 h at 37 degrees C. By increasing the lead
      acetate concentration in cell suspensions up to 50 microM for the same incubation
      time, the percentage of chemiluminescence inhibition was ca. 20%. It was shown
      that, after incorporating fluorescence probes in the membrane lipid bilayer of
      erythrocytes and lymphocytes treated with 10 and/or 50 microM lead acetate, the
      total fluorescence intensity and the excimer to monomer intensity ratio of PM
      decreased and the generalized fluorescence polarization of laurdan decreased by
      10-15%. The pyrene excimerization coefficient (kappa(ex)) increased by 20% (in
      comparison with a magnitude of kappa(ex) for white membranes isolated from intact
      erythrocytes) with 6-10 microM lead acetate for 3 h at 37 degrees C. The data
      obtained suggest that the effect of low concentrations of lead acetate does not
      cause production of ROS in erythrocytes in vitro, but can change the
      physicochemical state of proteins and lipids in erythrocyte and lymphocyte
      membranes. This effect is important because it influences the enzymatic activity
      and the functionality of receptors and channels present at the plasma membrane
      level, thus modulating the molecular composition of the intracellular space and
      cell functions.

PMID- 15744761
TI  - 'A little bitty spot and I'm a big man': patients' perspectives on refusing
      diagnosis or treatment for lung cancer.
AB  - Patient refusal of physicians' recommendations may partially account for
      variations in lung cancer treatment affecting survival. Reasons for refusal have
      not been well researched, and patients who refuse are often labeled derogatorily
      as irrational or enigmatically non-compliant. This study explored why patients
      refused recommendations for further diagnosis or treatment of lung cancer. We
      conducted in-depth interviews with nine patients, identified and recruited over a
      2-year period, with documented refusal of doctors' recommendations. Recruiting
      was hampered by deaths, logistics, and refusal to participate. Questions focused
      on participants' understanding of disease, medical recommendations, and
      perceptions of decision-making. Transcripts were analyzed using a grounded theory
      approach. Participants emphasized self-efficacy, minimizing threat, fatalism or
      faith, and distrust of medical authority; explanations were often multi
      dimensional. Comments included complaints about communication with physicians,
      health system discontinuities, and impact of social support. Explanations of
      participants' decisions reflected several ways of coping with an undesirable
      situation, including strategies for reducing, sustaining, and increasing
      uncertainty. Problematic Integration Theory helps to explain patients'
      difficulties in managing uncertainty when assessments of disease outcomes and
      treatment recommendations diverge. Implications for clinical communication
      include increasing trust while delivering bad news, understanding the source of
      resistance to recommendations, and discussing palliative care.

PMID- 15744762
TI  - Benefits of combining the sexes when evaluating data from toxicological studies.
AB  - In the assessment of the safety of a new drug, a large battery of toxicological
      studies is performed. In toxicological studies it is common practice to analyse
      the data from the sexes separately. We argue that this is not best practice and
      that much is to be gained from combining data from both sexes when evaluating
      studies. The main benefits and arguments in favour of combining the data are: (i)
      Improved efficiency, allowing fewer test animals and/or better precision. (ii)
      Other phases of drug development, clinical trials in particular, combine sexes.
      (iii) Most substances act similarly on both sexes and most drugs are prescribed
      without sex differentiation. (iv) If sex differences are of interest, combined
      data facilitates the quantification of the difference. (v) Reduced number of
      false positive and false negative findings. Although there might be some grounds
      to analysing the sexes separately, we argue that these are comparatively minor.
      We do not promote simply pooling the data and neglecting the existence of two
      sexes when comparing treatment groups. Rather, the analysis of combined data
      should allow for sex differences, for instance by using stratified procedures or
      by including a sex factor in a statistical model. We illustrate from real study
      data where the approach we propose has substantial benefits over traditional
      methods. A theoretical illustration is provided to quantify mathematically the
      potential gains and the corresponding sample size reduction, i.e. a reduction of
      animal use of ca. 50%, that would be possible without impairing the precision of
      studies.

PMID- 15744763
TI  - Stress ratio contributes to fatigue crack growth in dentin.
AB  - An experimental study of fatigue crack growth in dentin was conducted, and the
      influence of stress ratio (R) on the crack growth rate and mechanisms of cyclic
      extension were examined. Double Cantilever Beam (DCB) fatigue specimens were
      sectioned from bovine molars and then subjected to high cycle fatigue loading
      (10(5) < N < 10(6)) under hydrated conditions. The evaluation consisted of Mode I
      loads with stress ratios that ranged from -0.5 to 0.5. The fatigue crack growth
      rates were measured and used to estimate the crack growth exponent (m) and
      coefficient (C) according to the Paris Law model. The fatigue crack growth rates
      for steady-state extension (Region II) ranged from 1E-7 to 1E-4 mm/cycle. It was
      found that the rate of cyclic extension increased significantly with increasing
      R, and that the highest average crack growth rate occurred at a stress ratio of
      0.5. However, the crack growth exponent decreased with increasing R from an
      average of 4.6 (R = 0.10) to 2.7 (R = 0.50). The stress intensity threshold for
      crack growth decreased with increasing R as well. Results from this study suggest
      that an increase in the cyclic stress ratio facilitates fatigue crack growth in
      dentin and increases the rate of cyclic extension, both of which are critical
      concerns in minimizing tooth fractures and maintaining lifelong oral health.

PMID- 15744764
TI  - Differences in quality of life between non-Hodgkin's lymphoma survivors meeting
      and not meeting public health exercise guidelines.
AB  - The primary purpose of this study was to examine differences in quality of life
      (QoL) between non-Hodgkin's lymphoma (NHL) survivors meeting and not meeting
      public health exercise guidelines. A secondary purpose was to examine exercise
      behavior changes across three distinct cancer-related time periods (i.e.
      prediagnosis, on treatment and off treatment). Using a retrospective survey
      design, 438 NHL survivors residing in Alberta, Canada completed a mailed
      questionnaire that assessed self-reported exercise prediagnosis, on treatment and
      off treatment, and current QoL. Descriptive analyses indicated that 33.8, 6.5 and
      23.7% of NHL survivors met public health exercise guidelines during prediagnosis,
      on treatment, and off treatment time periods, respectively. Multivariate analyses
      of variance indicated that NHL survivors meeting public health exercise
      guidelines during postdiagnosis time periods had higher current QoL scores than
      NHL survivors not meeting guidelines. QoL difference scores between the two
      groups met proposed standards for clinically important differences. Multivariate
      analyses also indicated significant differences in exercise behavior across the
      three cancer-related time periods (all p's<0.01). These analyses were unchanged
      after statistically controlling for important medical and demographic variables.
      The results of this study provide evidence that NHL survivors meeting public
      health exercise guidelines on and off treatment reported higher current QoL than
      those survivors not meeting guidelines. These findings corroborate research
      examining exercise behavior in other cancer survivor groups and provide
      preliminary data to support a randomized controlled trial on exercise and QoL in
      this population.

PMID- 15744765
TI  - New allosteric modulators of metabotropic glutamate receptor 5 (mGluR5) found by
      ligand-based virtual screening.

PMID- 15744767
TI  - Fluorous base-pairing effects in a DNA polymerase active site.
AB  - We describe selective "fluorous" effects in the active site of a DNA polymerase,
      by using nucleotide analogues whose pairing edges are perfluorinated. The 5'
      triphosphate deoxynucleotide derivatives of DNA base analogues 2,3,4,5
      tetrafluorobenzene ((F)B) and 4,5,6,7-tetrafluoroindole ((F)I), as well as
      hydrocarbon controls benzene (B) and indole (I), were synthesized and studied as
      substrates for the DNA Polymerase I Klenow fragment (KF exo-). Modified
      nucleotides were present in the DNA template or were supplied as nucleoside
      triphosphates in studies of the steady-state kinetics of single nucleotide
      insertion. When supplied opposite the non-natural bases in the template strand,
      the hydrophobic nucleoside triphosphates were incorporated by up to two orders of
      magnitude more efficiently than the natural deoxynucleoside triphosphates. The
      purine-like fluorinated indole nucleotide ((F)I) was the most efficiently
      inserted of the four hydrophobic analogues, with the most effective incorporation
      occurring opposite the pyrimidine-like tetrafluorobenzene ((F)B). In all cases,
      the polyfluorinated base pairs were more efficiently processed than the analogous
      hydrocarbon pairs. A preliminary test of polymerase extension beyond these pairs
      showed that only the (F)B base is appreciably extended; the inefficient extension
      is consistent with recently published data regarding other nonpolar base pairs.
      These results suggest the importance of hydrophobicity, stacking, and steric
      interactions in the polymerase-mediated replication of DNA base pairs that lack
      hydrogen bonds. These findings further suggest that the enhanced hydrophobicity
      of polyfluoroaromatic bases could be employed in the design of new, selective
      base pairs that are orthogonal to the natural Watson-Crick pairs used in
      replication.

PMID- 15744766
TI  - The effects of ligand exchange and mobility on the peroxidase activity of a
      bacterial cytochrome c upon unfolding.
AB  - The effect on the heme environment upon unfolding Paracoccus versutus
      ferricytochrome c-550 and two site-directed variants, K99E and H118Q, has been
      assessed through a combination of peroxidase activity increase and one
      dimensional NMR spectroscopy. At pH 4.5, the data are consistent with a low- to
      high-spin heme transition, with the K99E mutation resulting in a protein with
      increased peroxidase activity in the absence of or at low concentrations of
      denaturant. Furthermore, the mobility of the polypeptide chain at pH 4.5 for the
      wild-type protein has been monitored in the absence and presence of denaturant
      through heteronuclear NMR experiments. The results are discussed in terms of
      local stability differences between bacterial and mitochondrial cytochromes c
      that are inferred from peroxidase activity assays. At pH 7.0, a mixture of
      misligated heme states arising from protein-based ligands assigned to lysine and
      histidine is detected. At low denaturant concentrations, these partially unfolded
      misligated heme forms inhibit the peroxidase activity. Data from the K99E
      mutation at pH 7.0 indicate that K99 is not involved in heme misligation, whereas
      histidine coordination is proven by the data from the H118Q variant.

PMID- 15744768
TI  - Understanding the conformational dependence of spin-spin coupling constants:
      through-bond and through-space J(31P,31P) coupling in tetraphosphane-1,4-diides
      [M(L)x]2[P4R4].
AB  - The characteristic dependence of J(31P,31P) spin-spin coupling constants of
      alkali metal tetraphosphane-1,4-diides on structure and composition has been
      analyzed by density functional methods. The computations confirm that the
      structure of the contact ion pairs is conserved in solution. Calculations on
      model systems M2P4H4, on naked P4H4(2-) anions, and on models including point
      charges, show that the role of the cations is mainly structural and to a smaller
      extent electrostatic. Three of the four J(P,P) coupling constants depend
      characteristically on the conformation of the anion, which in turn is determined
      by the substituents R and by cation-anion interactions. Several couplings exhibit
      a large through-space component and are thus strongly dependent on the relative
      orientation of nonbonding electron pairs on the phosphorus atoms involved. This
      is shown by visualization of coupling pathways using the recently introduced
      coupling energy density (CED), in combination with the electron localization
      function (ELF).

PMID- 15744769
TI  - Heme alkylation by artesunic acid and trioxaquine DU1301, two antimalarial
      trioxanes.
AB  - The sesquiterpene Artemisinin, an antimalarial drug that is effective against
      multidrug-resistant Plasmodium falciparum strains, contains a 1,2,4-trioxane, and
      the endoperoxide function plays a key role in its biological activity. However,
      its poor solubility means that hemisynthetic derivatives, such as artesunic acid,
      are preferred for drugs. The reductive activation of the peroxide function of
      artemisinin by iron(II)-heme produces heme derivatives that are alkylated at meso
      positions by a C-centered radical derived from artemisinin. We checked if the
      alkylating ability of trioxane-based drugs toward heme, which might be related to
      its parasiticidal activity, is a general feature by comparing the chemical
      reactivity toward heme of the clinically relevant derivative artesunic acid and
      DU1301, a drug of the trioxaquine family, that is active against P. falciparum.
      Both artesunic acid and trioxaquine DU1301 efficiently alkylated the heme
      macrocycle after activation of their peroxide function by the iron(II) of heme
      itself and thus gave rise to covalently coupled heme-drug products. This heme
      drug adduct formation might be related to the high antimalarial activity of
      DU1301.

PMID- 15744770
TI  - Nanoscale imaging and quantification of local proteolytic activity.
AB  - Proteolytic cleavage of extracellular matrix (ECM) is a critical feature of tumor
      cell invasion, and affects cancer cell growth, differentiation, apoptosis, and
      migration. Malignant cells secrete most proteases as inactive proenzymes that
      undergo proteolytic cleavage for activation, and proteolytic activity is elevated
      in close proximity to these cells. Therefore, local activity rather than protease
      concentration determines ECM proteolysis. Precise quantification of local
      proteolytic activity, functional investigation, and high resolution imaging of
      morphological ECM alterations have proven difficult. In this study, we present a
      novel approach for measuring proteolytic activity in the microenvironment of
      cells by using atomic force microscopy (AFM). Amelanotic melanoma cells (A7
      clone) were seeded on fluorescent gelatin or collagen-IV coatings. Proteolysis
      reduced fluorescence of these coatings. Fluorescence microscopy (FM) in
      combination with AFM was used to maneuver the AFM-tip to tumor cell induced
      proteolytic spots. AFM enabled nanoscale volume measurement, three-dimensional
      reconstruction of single proteins and demonstrated that ECM cleavage is
      restricted to the proteolytic microenvironment of cancer cells. This method
      detected significant decreases in molecular weight of protein clusters (-76.6%),
      matrix volume (-46.6%), and height (-38.1%) between intact and proteolyzed
      gelatin. Similar parameter changes were demonstrated without FM, by AFM-scanning
      gelatin in close proximity to invasive cells. Furthermore, AFM depicted
      significantly stronger local degradation of gelatin than collagen-IV by A7-cells.
      Taken together, AFM allows specific quantification and imaging of local
      proteolytic processes at a nanometer level, thus providing a unique method for
      the functional evaluation of invasiveness and metastatic potential of tumor cells
      in small scale samples.

PMID- 15744771
TI  - Multistate reactivity in styrene epoxidation by compound I of cytochrome p450:
      mechanisms of products and side products formation.
AB  - Density functional theoretical calculations are used to elucidate the epoxidation
      mechanism of styrene with a cytochrome P450 model Compound I, and the formation
      of side products. The reaction features multistate reactivity (MSR) with
      different spin states (doublet and quartet) and different electromeric situations
      having carbon radicals and cations, as well as iron(III) and iron(IV) oxidation
      states. The mechanisms involve state-specific product formation, as follows: a)
      The low-spin pathways lead to epoxide formation in effectively concerted
      mechanisms. b) The high-spin pathways have finite barriers for ring-closure and
      may have a sufficiently long lifetime to undergo rearrangement and lead to side
      products. c) The high-spin radical intermediate, (4)2(rad)-IV, has a ring closure
      barrier as small as the C--C rotation barrier. This intermediate will therefore
      lose stereochemistry and lead to a mixture of cis and trans epoxides. The
      barriers for the production of aldehyde and suicidal complexes are too high for
      this intermediate. d) The high-spin radical intermediate, (4)2(rad)-III, has a
      substantial ring closure barrier and may survive long enough time to lead to
      suicidal, phenacetaldehyde and 2-hydroxostyrene side products. e) The
      phenacetaldehyde and 2-hydroxostyrene products both originate from crossover from
      the (4)2(rad)-III radical intermediate to the cationic state, (4)2(cat,z(2) ).
      The process involves an N-protonated porphyrin intermediate that re-shuttles the
      proton back to the substrate to form either phenacetaldehyde or 2-hydroxostyrene
      products. This resembles the internally mediated NIH-shift observed during
      benzene hydroxylation.

PMID- 15744772
TI  - Regulatory networks for the control of body iron homeostasis and their
      dysregulation in HFE mediated hemochromatosis.
AB  - Although the recent identification of several genes has extended our knowledge on
      the maintenance of body iron homeostasis, their tissue specific expression
      patterns and the underlying regulatory networks are poorly understood. We studied
      C57black/Sv129 mice and HFE knockout (HFE -/-) variants thereof as a model for
      hemochromatosis, and investigated the expression of iron metabolism genes in the
      duodenum, liver, and kidney as a function of dietary iron challenge. In HFE +/+
      mice dietary iron supplementation increased hepatic expression of hepcidin which
      was paralleled by decreased iron regulatory protein (IRP) activity, and reduced
      expression of divalent metal transporter-1 (DMT-1) and duodenal cytochrome b
      (Dcytb) in the enterocyte. In HFE -/- mice hepcidin formation was diminished upon
      iron challenge which was associated with decreased hepatic transferrin receptor
      (TfR)-2 levels. Accordingly, HFE -/- mice presented with high duodenal Dcytb and
      DMT-1 levels, and increased IRP and TfR expression, suggesting iron deficiency in
      the enterocyte and increased iron absorption. In parallel, HFE -/- resulted in
      reduced renal expression of Dcytb and DMT-1. Our data suggest that the feed back
      regulation of duodenal iron absorption by hepcidin is impaired in HFE -/- mice, a
      model for genetic hemochromatosis. This change may be linked to inappropriate
      iron sensing by the liver based on decreased TfR-2 expression, resulting in
      reduced circulating hepcidin levels and an inappropriate up-regulation of Dcytb
      and DMT-1 driven iron absorption. In addition, iron excretion/reabsorption by the
      kidneys may be altered, which may aggravate progressive iron overload.

PMID- 15744774
TI  - Comparison of different test models for the assessment of cytotoxicity of
      composite resins.
AB  - This study compared the use of different test models to assess the cytotoxicity
      of a dental composite. The cytotoxicity of a composite polymerized using two
      halogen-based light-curing units (LCUs) (Max LC and Astralis) and two light
      emitting diode LCUs (E-light and Freelight) served as the basis of comparison.
      Disk-shaped specimens (7 mm diameter, 2 mm high) were fabricated using the four
      different light sources. The specimens were used in several cytotoxicity test
      models: direct and indirect contact tests as well as an extract test with an
      established cell line L-929. The cells were stained with neutral red after cell
      material contact for 48 h. Neutral red-stained areas (in mm2, for direct and
      indirect tests) and absorbance readings (for extract tests) were analysed
      statistically using ANOVA and the Tukey post hoc test, with P < 0.05 considered
      to be significantly different. Good correlation between direct and indirect
      contact tests (r = 0.903) was found. The extract test was the least correlated
      among the three tests. It was found that the E-light + Freelight-cured composite
      elicited cytotoxicity from the correlated studies. Uncured specimens were most
      detrimental to the cells in all tests. Our data demonstrated that composite cured
      with light-emitting diode LCUs were cytotoxic to L-929 cells. Different test
      models were found to give rise to different findings. Thus, a good cell-material
      contact method would replicate more closely the physiological situation in vivo.
      This in turn would give more clinically relevant results.

PMID- 15744773
TI  - Characterization of five evolutionary conserved regions of the human tyrosine
      hydroxylase (TH) promoter: implications for the engineering of a human TH minimal
      promoter assembled in a self-inactivating lentiviral vector system.
AB  - A DNA fragment of about 13 kb containing the human tyrosine hydroxylase (TH)
      promoter was previously isolated from a genomic DNA library and sequenced. The 11
      kb from the transcription start of the human TH promoter was successively joined
      to the green fluorescent protein (GFP) to generate a transgenic mouse model. High
      levels of GFP expression could be observed in TH-positive cells of the Substantia
      nigra of embryonic and adult mice. Intriguingly, the sequence of the human TH
      promoter showed a low degree of homology with the mouse and rat TH promoters. In
      fact, comparative analysis of the sequences of human, rat, and mouse TH promoters
      revealed only five small regions of high homology. These five evolutionarily
      conserved regions were numbered in numeric progression from the 5' end of human
      TH promoter. In the present study, a panel of minimal human TH promoters was
      generated to analyze the transcriptional activity and specificity of gene
      expression conferred by the five conserved regions (CRs). The series of
      constructs was termed 250 bp and contained the first -194 bp of the human TH
      promoter immediately upstream of the transcription start, the first 35 bp the
      human TH messenger RNA leader, plus one or more of the five CRs. All the
      constructs were assembled in a self-inactivating form of the latest series of
      lentiviral vector system based on the human immunodeficiency virus type 1 (HIV
      1). Lentiviral-mediated gene transfer was highly efficient for the in vitro
      transduction of human neuronal progenitor cells (hNPCs). Since a subset of hNPCs
      express TH following in vitro treatment with a mixture of differentiating agents,
      it was possible to assess specificity of expression for all the minimal human TH
      promoters. Overall, the successive addition of the five conserved regions
      produced a greater degree of specificity in induced TH-positive hNPCs, in
      particular after the addition of CRI (-8,917, -8,876). However, the human TH
      minimal promoters did not show any specificity for TH-positive differentiated
      mouse primary striatal and S. nigra cells, indicating a difference of TH gene
      regulation between the human and mouse systems. The human TH minimal promoters
      may provide the opportunity for the selection of TH-positive human embryonic and
      adult stem cells for brain transplantation experiments in animal models for
      Parkinson's disease.

PMID- 15744775
TI  - Regulatory and necrotic volume increase in boar spermatozoa.
AB  - Spermatozoa of many species initially respond to hypotonicity as perfect
      osmometers. Thereafter they undergo a regulatory process resulting in a decrease
      in cell volume, similar to that reported for somatic cells. Regulatory volume
      increase (RVI), a complementary process which is assumed to occur following
      initial shrinkage of sperm volume after exposure to a hypertonic medium, has not
      yet been described in detail for spermatozoa. In this study, we investigated
      whether spermatozoa are able to regulate their volume after hypertonic stress and
      whether this ability is maintained in preserved sperm. Cell volume changes were
      recorded using electronic cell sizing. Sperm response to the ion channels
      blockers quinidine, tamoxifen, and dydeoxyforskolin, and to protein
      kinase/phosphatase inhibitors lavendustin, staurosporine, and vanadate was
      studied to investigate possible mechanisms of RVI. Annexin V staining was used in
      combination with propidium iodide to determine whether hypertonic stress may
      induce apoptosis. Overall protein tyrosine phosphorylation under hypertonic
      conditions was measured via flow cytometry using antiphosphotyrosine antibody.
      Spermatozoa exposed to hypertonic stress initially responded with an abundant
      subpopulation according to the perfect osmometer model and recovered their volume
      from this shrinkage after 20 min. RVI was inhibited by quinidine and tamoxifen,
      which indicates the involvement of the important cellular ions sodium and
      chloride in this process. Volume regulatory ability was essentially maintained
      during storage of liquid semen. However, the response of the sperm population was
      heterogeneous. A second population raised, containing spermatozoa with larger
      volumes, which demonstrated irregularities in the volume response with respect to
      osmotic challenge, ion channel blockers, and storage. Under hypertonic
      conditions, both protein kinase inhibitors (PKI) led to increased isotonic
      volumes and to elevated initial relative volumes and subsequent volume decrease.
      RVI was inhibited by the vanadate. Hypertonic stress did not result in an
      increase in early apoptotic cells, but produced a shift toward late necrotic
      cells. Substitution of sodium and chloride by choline and sulfate resulted in
      decreased isotonic volume of sperm treated with lavendustin. Tyrosine
      phosphorylation levels were reduced after 20 min under hypertonic conditions. It
      was concluded that RVI is regulated via a protein tyrosine kinase-dependent
      pathway, and that dephosphorylation occurs when volume regulation is required.
      The necrotic volume increase (NVI) is associated with the accumulation of sodium
      and chloride following uncontrolled opening of the channels. The ability to
      regulate volume after exposure to hypertonic conditions is important for sperm
      functionality and can have practical applications in spermatological diagnostics
      and cryopreservation.

PMID- 15744776
TI  - Solid tissues can be manipulated ex vivo and used as vehicles for gene therapy.
AB  - BACKGROUND: Organ fragments can be cultured for weeks in vitro if they are
      prepared of microscopic thickness and if the basic organ structure is preserved.
      Such organ fragments, which we termed micro-organs (MOs), express in culture
      endogenous tissue-specific gene products. We have exploited this methodology to
      engineer MOs ex vivo by gene transfer. METHODS: MOs prepared from spleen, lung,
      colon and skin were infected using: herpes simplex type-1, adeno virus, vaccinia
      virus and murine leukemia virus (MuLV), carrying the reporter gene beta
      galactosidase. RESULTS: All four viral vectors infected MOs in culture, with
      adeno infection giving significantly higher values. After optimization, high
      levels of expression (> 15% positive cells), comparable to those obtained with
      the adeno construct, were also obtained using the MuLV construct both in vitro
      and after implantation into syngeneic hosts. After implantation, the engineered
      tissue was found to remain localized, become vascularized, and to express the
      transduced gene for several months. CONCLUSIONS: The system can be used to study
      interactions between viruses and tissues both ex vivo and in vivo. Furthermore,
      the approach proposes a novel platform for ex vivo gene therapy. Such engineered
      structures could be used as autologous biological pumps for continuous secretion
      in vivo of gene products of clinical importance.

PMID- 15744778
TI  - Perceived growth and decline following breast cancer: a comparison to age-matched
      controls 5-years later.
AB  - Research indicates that individuals who experience stressful life events, such as
      a diagnosis of cancer, often experience both positive and negative changes as a
      result of their experiences, but little research has compared these changes with
      those of a control group who have experienced other stressful life events. We
      compared 184 5-year breast cancer survivors (Stages: I, II, and III; 95%
      Caucasian) with 184 age-matched controls in terms of perceived growth and decline
      that stem from stressful events. Survivors reported on their experience with
      cancer, whereas controls identified the most stressful event that happened to
      them 5 years ago. Survivors reported more growth (e.g. appreciation of life) and
      more decline (e.g. physical side effects) compared with controls. However, there
      were no group differences in reports of psychological stress. When survivors were
      compared with controls whose stressor was a personal health problem, many of the
      differences in growth between the two groups remained, but the differences in
      decline disappeared. These findings suggest that some growth is unique to breast
      cancer, but much of the decline associated with breast cancer is similar to the
      decline associated with other types of health problems.

PMID- 15744777
TI  - The psychological impact of mammographic screening on women with a family history
      of breast cancer--a systematic review.
AB  - This systematic review aims to assess the psychological impact of mammographic
      screening on women with a family history of breast cancer. Women with a family
      history, and hence increased risk, of breast cancer are known to experience
      higher levels of anxiety about cancer. They are also often offered screening from
      an earlier age. The psychological consequences of screening are therefore of
      particular importance for this group of women. A comprehensive search of 4
      electronic databases was conducted from 1982 to 2003, combining sets of terms
      relating to (1) breast screening or mammography (breast screen*; mammogra*), (2)
      psychological impact (adverse effects; anxi*; distress; nervous; psych*,
      psychological consequences; stress; worry) and (3) family history. Reference
      lists from relevant papers were examined for additional papers. The review
      identified seven papers from four countries. Overall, the findings indicate that,
      similar to women in the general population, most women with a family history do
      not appear to experience high levels of anxiety associated with mammographic
      screening. Although women who are recalled for further tests do experience
      increased anxiety the levels appear to be no greater than for women without a
      family history. We conclude that further research on this topic is required--this
      should include studies designed specifically to consider both the negative and
      positive impact of mammographic screening on women with a family history, using
      validated measures of anxiety and worry in combination with qualitative research.

PMID- 15744780
TI  - A qualitative study of work and work return in cancer survivors.
AB  - Few studies have examined the impact of cancer on the survivor's quality of work
      life. The purpose of this qualitative study is to describe the work experiences
      among a diverse group of cancer survivors and to explore factors influencing
      decisions about work after cancer diagnosis and treatment. We interviewed 28
      participants with a broad range of socioeconomic backgrounds and primary cancer
      sites. Qualitative results indicate that after learning about their cancer
      diagnosis, participants had diverse and complex patterns of work return and work
      change, and experienced a variety of factors that influenced post-cancer
      decisions. Experiences at work after cancer also varied in relation to how others
      responded, changes in productivity, effects of cancer and treatment on work, and
      feelings about work. Most respondents received little guidance from their
      physicians about work, and many participants described their cancer as impacting
      their priority of work relative to other aspects of their lives. Our findings
      reinforce the complexity of measuring employment outcomes and the range of
      adaptations made to improve the quality of work life. Additional research is
      needed to identify prognostic factors that can guide clinical or workplace
      efforts to restore cancer survivors to their desired level of work function and
      economic productivity.

PMID- 15744779
TI  - Is perceived social support a predictor of survival for patients undergoing
      autologous peripheral blood stem cell transplantation?
AB  - PURPOSE: Previous research discussed the predictive value of psychosocial
      variables along with biomedical predictors for survival; such as affective
      functioning and quality of life. The present study addresses the following
      research question: does perceived social support prior to PSBCT have an impact on
      post-transplant survival? SUBJECTS AND METHODS: Ninety-nine patients suffering
      from Multiple Myeloma (n=55), Non-Hodgkin Lymphoma (n=33), and other malignancies
      (n=11) completed the Illness Specific Scales of Social Support (ISSS) before
      undergoing PBSCT. ISSS is comprised of the subscales 'positive social support'
      and 'problematic social support', e.g. criticising, victimising, or avoiding
      interactions. RESULTS: The mean score in the subscale 'positive social support'
      was 3.2 (S.D. 0.54; range 0 until 4), in the subscale 'negative social support'
      0.94 (S.D. 0.53). There was no association between positive interactions and
      survival following PBSCT. Conversely, those patients perceiving problematic
      social support, showed a correspondence with poor survival following PBSCT
      (RR=3.649; p=0.015; Cox-regression analysis). The following variables were
      controlled: Karnofsky Performance Status, interferon treatment, depression and
      participation in psychotherapy. CONCLUSION: Differentiating between positive and
      problematic interactions prior to PBSCT helps to recognise detrimental forms of
      social support. Future research should investigate the clinical implications and
      help tailor psychotherapeutic intervention.

PMID- 15744781
TI  - Brief report: etiological attributions for breast cancer among healthy African
      American and European American women.
AB  - Anecdotal evidence suggests that African American women's attributions about
      breast cancer may differ from European American women, but empirical studies are
      lacking. The present study examined attributions about breast cancer made by a
      sample of healthy African American and European American women. The sample
      included 197 women (75 African American, 122 European American), with a mean age
      of 39.2. Overall, women were most likely to attribute the development of breast
      cancer to genetics, "no one", environmental poisons, diet, personal behavior and
      stress. European American women were more likely to attribute breast cancer to
      broadly external causes such as the environment, heredity and chance, while
      African American women were more likely to list immediate, interpersonal-level
      causes such as a blow to the breast, and personal behavior. Results highlight the
      need for attention to cultural processes in cancer prevention and control.

PMID- 15744782
TI  - Diverse isoforms of colony-stimulating factor-1 have different effects on the
      development of stroma-dependent hematopoietic cells.
AB  - Maintenance and differentiation of hematopoietic stem and progenitor cells are
      controlled by complex interactions with the stroma microenvironment. Stroma-cell
      interactions can be supported by locally expressed membrane-spanning cell-surface
      (cs) growth factors. CSF-1 is expressed by stroma as a soluble glycoprotein, as
      proteoglycan, or as a membrane-spanning cs glycoprotein. CSF-1 regulates the
      survival, proliferation, and differentiation of mononuclear phagocytes. Whereas
      the biological role of soluble CSF-1 is well characterized, the function of the
      membrane-spanning cell-surface CSF-1 (csCSF-1) remains unclear. To analyze the
      biological significance of csCSF-1 in vitro, we used an epithelial cell line to
      ectopically express the different CSF-1 isoforms. In co-cultures of CSF-1
      transduced epithelial cells with primary, early hematopoietic progenitor cells we
      examined whether interaction between csCSF-1 and its receptor mediates cell
      proliferation, self-renewal, or differentiation. csCSF-1 induces long-lasting
      proliferation of stimulated cells and furthermore supports self-renewal. Ectopic
      secretion of soluble CSF-1 does not permit long-term growth of progenitor cells
      but induces differentiation of monocytes into macrophages. Previously, we showed
      that the soluble and cs isoforms of stroma-encoded SCF differently affect the
      development of hematopoietic cells. Cell-surface SCF (csSCF) promotes self
      renewal of stimulated cells whereas soluble SCF causes clonal extinction. These
      results and those presented here for CSF-1 provide evidence for diverse functions
      of the isoforms of the ligands SCF and CSF-1 for two tyrosine kinase receptors of
      the subclass III both regulating hematopoiesis on stroma.

PMID- 15744783
TI  - Discoloration of dental resin composites after immersion in a series of organic
      and chemical solutions.
AB  - The objective of this study was to evaluate the color change of dental resin
      composites following a series of immersion treatments, especially in organic
      substances. The color of four resin composites was measured according to the
      CIELAB color scale relative to the standard illuminant D65. Color was measured at
      baseline, and after sequential immersion in the following substances: Step 1,
      porcine-liver esterase (a substitute for a salivary esterase); Step 2, organic
      substances (mucin and serum) and phosphate-buffered saline (PBS) as a control;
      Step 3, chemical alteration agents [chlorhexidine (CH) and carbamide peroxide
      (CP)]; and Step 4, 2% methylene blue. Porcine-liver esterase caused color changes
      (DeltaE(ab) (*)) of 0.7-1.1 from the baseline. Organic substances caused color
      changes of 0.4-1.8 from the baseline, and color changes in organic substances
      were not significantly higher than those in PBS (p > 0.05), except for one
      composite. Combined treatment with mucin (or serum) with CH (or CP) did not
      produce significantly higher color changes compared to controls (p > 0.05). Mucin
      treated composites showed generally lower methylene blue staining compared to
      serum and PBS groups. Although combined treatment of organic substances and
      chemical agents resulted in various discolorations of resin composites, chemical
      alteration of organic substances did not produce higher color change compared to
      PBS controls.

PMID- 15744784
TI  - Regulation of manganese accumulation in perinatally exposed rat pups.
AB  - The risk of manganese (Mn)-related ill effects in the neonate has been the topic
      of several investigations because in formula-fed infants Mn intake is much higher
      than in breast-fed infants. In the young, when Mn homeostasis is not yet
      developed, increased Mn intake might pose a neurotoxic risk. Our work aimed at
      collecting new data on Mn accumulation during the perinatal period by using an
      experimental rat model in pups whose mothers were exposed orally to Mn in drink
      (as manganese chloride; dose of 2000 ppm Mn) throughout pregnancy and 11 days of
      lactation. Pups were cross-fostered at birth and placental and mammary transfer
      of Mn at birth and at the age of 11 days was evaluated. The total pup body burden
      of Mn was analysed by atomic absorption spectrometry. Concentrations of iron
      (Fe), zinc (Zn) and calcium (Ca) also were analysed at the end of the experiment.
      The concentration of Mn in perinatally exposed pups was 6-8 times higher than in
      controls, irrespective of the period and duration of exposure. After cessation of
      exposure, the Mn concentration decreased almost to control levels. Concentrations
      of other essential elements (Fe, Zn, Ca) were not affected by Mn exposure. Our
      results indicate the existence of an accurate regulation of Mn accumulation in
      pups exposed to Mn during the perinatal period.

PMID- 15744785
TI  - Etoposide-induced cytogenotoxicity in mouse spermatogonia and its potential
      transmission.
AB  - As cancer chemotherapeutic agents are cytogenotoxic but not target-specific
      during systemic treatment, they affect all the encountered cells including the
      non-cancerous ones and consequently lead to the recurrence of second malignancy
      in post-chemotherapeutic cancer survivors. The effects would be persistent if the
      stem cells were affected. These drugs also may affect germline cells during
      therapeutic treatments. There is every chance that the effects are transmitted
      through the germline cells to the gametes and to the next generation if the
      gonadal mother cells are affected. Such transmission of effects from the post
      chemotherapeutic childhood cancer survivors is of serious concern but very little
      attention has been given so far to such studies. Etoposide (VP-16)--a semi
      synthetic epipodophyllotoxin derivative, a DNA non-intercalating agent and a
      topoisomerase II inhibitor--is prescribed frequently for the treatment of various
      types of cancers. It is a potent clastogen inducing chromosomal damage both in
      vitro and in vivo. Its clastogenic effect is indirect through inhibition of the
      catalytic activity of topoisomerase II enzymes, which maintain the topology of
      DNA during replication, recombination, transcription, etc. by forming a
      'cleavable complex' and facilitate the cleaving and re-ligation of the cleaved
      DNA to relieve the torsional stress during such events. Transient stabilization
      of the cleavable complex by etoposide leads to illegitimate ligation of the
      cleaved DNA. Consequently, single- and double-strand breaks occur. In the present
      study, the clastogenic potential of three different doses of etoposide (10, 15
      and 20 mg kg(-1)) in the male germline of mice was assessed from the dividing
      spermatogonia after a single exposure for one cell cycle duration at 24 h post
      treatment. Transmission of such effects was assessed from the frequency of
      aberrant primary spermatocytes at week 4 post-treatment and of abnormal sperm at
      week 8 post-treatment. All three doses of etoposide were found to be clastogenic
      to the dividing spermatogonia of mice, and mostly chromatid breaks were induced.
      The effects also were transmitted through the male germline of mice, which was
      evident from the prevalence of statistically significant increased percentages of
      aberrant primary spermatocytes at week 4 posttreatment and the higher percentages
      of abnormal sperm at week 8 post-treatment. Thus, there is every chance that the
      cytogenotoxic effects of etoposide are transmitted to the next generation through
      the male germline of post-chemotherapeutic cancer survivors, therefore it is
      essential to make etoposide target-specific or modulate its effects.

PMID- 15744786
TI  - Hereditary melanoma and predictive genetic testing: why not?
AB  - BACKGROUND: Since p16-Leiden presymptomatic testing for hereditary melanoma has
      become available in the Netherlands, the benefits and risks of offering such
      testing are evaluated. The current paper investigated why the non-participants
      were reluctant to participate in genetic testing. METHODS: Sixty six eligible
      individuals, who were knowledgeable about the test but had not participated in
      genetic testing by January 2003, completed a self-report questionnaire assessing
      motivation, anxiety, family dynamics, risk knowledge and causal attributions.
      RESULTS: Non-participants reported anxiety levels below clinical significance. A
      principal components analysis on reasons for non-participation distinguished two
      underlying motives: emotional and rational motivation. Rational motivation for
      non-participation was associated with more accurate risk knowledge, the
      inclination to preselect mutation carriers within the family and lower scores on
      anxiety. Emotional motivation for non-participation was associated with disease
      misperceptions, hesitation to communicate unfavourable test results within the
      family and higher scores on anxiety. CONCLUSION: Rational and emotional
      motivation for non-participation in the genetic test for hereditary melanoma was
      found. Emotionally motivated individuals may be reluctant to disseminate genetic
      risk information. Rationally motivated individuals were better informed than
      emotionally motivated individuals. It is suggested that a leaflet is added to the
      invitation letter to enhance informed decision-making about genetic testing.

PMID- 15744787
TI  - Emotional and behavioural functioning of children of a parent diagnosed with
      cancer: a cross-informant perspective.
AB  - This study investigates emotional and behavioural problems in children of parents
      diagnosed with cancer and examines the relationship with demographic and illness
      related variables. Furthermore, agreement and differences between informants
      regarding child's functioning were examined. Members of 186 families in which a
      parent had been diagnosed with cancer participated. More emotional problems were
      reported for latency-aged sons (ill parents) and adolescent daughters (ill
      parents; self-reports), whereas also better functioning was reported in
      adolescent children (spouses), compared to the norm group. Age and gender-effects
      were found: latency-aged sons were perceived as having more emotional problems
      than adolescent sons (ill parents); adolescent daughters as having more emotional
      and behavioural problems than adolescent sons (ill parents; self-reports).
      Results indicated a higher prevalence of problems when the father was ill than
      when the mother was (spouses and self-reports). The treatment intensity affected
      adolescent daughter's functioning (spouses), whereas adolescent son's functioning
      was affected by relapsed disease (self-reports). Adolescents and mothers
      perceived comparable levels of problems, but fathers perceived problems in
      children to be less prevalent. Findings suggest that adolescent daughters and
      latency-aged sons are at risk for emotional problems following the diagnosis of
      cancer in a parent. The perception of child's functioning and potential
      influencing variables varied according to informant.

PMID- 15744788
TI  - Conclusive determination of the absolute configuration of chiral C60-fullerene
      cis-3 bisadducts by X-ray crystallography and circular dichroism.

PMID- 15744789
TI  - A concept for rapid protein-structure determination by solid-state NMR
      spectroscopy.

PMID- 15744790
TI  - [Pb5{Mo(CO)3}2]4-: a complex containing a planar Pb5 unit.

PMID- 15744791
TI  - [(Eta6-B6X)2M] (X=C, N; M=Mn, Fe, Co, Ni): a new class of transition-metal
      sandwich-type complexes.

PMID- 15744792
TI  - Crystal-to-crystal transformation from a chain polymer to a two-dimensional
      network at low temperatures.

PMID- 15744793
TI  - Periodic mesoporous organosilicas: self-assembly from bridged cyclic
      silsesquioxane precursors.

PMID- 15744794
TI  - The preparation of mesoscopic rings in colloidal crystal templates.

PMID- 15744795
TI  - Day care versus in-patient surgery for age-related cataract.
AB  - BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness
      in the world with the majority of people who are blind from cataract found in the
      developing world. With the increased number of people with cataract there is an
      urgent need for cataract surgery to be made available as a day care procedure.
      OBJECTIVES: To provide reliable evidence regarding the safety, feasibility,
      effectiveness and cost-effectiveness of cataract extraction performed as day care
      versus in-patient procedure. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and
      Vision Group Trials Register) on The Cochrane Library (Issue 3 2004), MEDLINE
      (1966 to July 2004), EMBASE (1980 to August 2004) and LILACS (July 2004).
      SELECTION CRITERIA: This review includes randomised controlled trials comparing
      day care and in-patient surgery for age-related cataract. The primary outcome was
      the achievement of a satisfactory visual acuity six weeks after the operation.
      DATA COLLECTION AND ANALYSIS: Although two trials are included in the review,
      adequate data were available for only one trial and therefore pooling of data
      from studies was not attempted. A descriptive summary is presented. MAIN RESULTS:
      Two trials, involving a total of 1284 people, are included in this review. One
      trial reported statistically significant differences in early postoperative
      complication rates in the day care group, with an increased risk of increased
      intraocular pressure, which had no clinical relevance to visual outcomes four
      months postoperatively. The mean change in visual acuity (Snellen lines) of the
      operated eye four months postoperatively was 4.1 (standard deviation (SD) 2.3)
      for the day care group and 4.1 (SD 2.2) for the in-patient group and not
      statistically significant. The four-month postoperative mean change in quality of
      life score measured using the VF14 showed minimal differences between the two
      groups. Costs were 20% more for the in-patient group and this was attributed to
      higher costs for overnight stay. One study only reported hotel costs for the non
      hospitalised participants making aggregation of data on costs impossible.
      AUTHORS' CONCLUSIONS: This review provides some evidence that there is a cost
      saving but no significant difference in outcome or risk of postoperative
      complications between day care and in-patient cataract surgery. This is based on
      one detailed and methodologically sound trial conducted in the developed world.
      The success, safety and cost-effectiveness of cataract surgery as a day care
      procedure appear to be acceptable but additional well-designed trials are
      required to confirm these perceptions.

PMID- 15744797
TI  - Attaining exponential convergence for the flux error with second- and fourth
      order accurate finite-difference equations. I. Presentation of the basic concept
      and application to a pure diffusion system.
AB  - It is a well-known phenomenon called superconvergence in the mathematical
      literature that the error level of an integral quantity can be much smaller than
      the magnitude of the local errors involved in the computation of this quantity.
      When discretizing an integrated form of Fick's second law of diffusion the local
      errors reflect the accuracy of individual concentration points while the integral
      quantity has the physical meaning of the flux. This article demonstrates how an
      extraordinary fast exponential convergence towards zero can be achieved for the
      simulated flux error on the basis of finite-difference approximations that are
      only second-order (Box 2 method) or fourth-order (Box 4 method) accurate as far
      as the level of local errors is concerned.

PMID- 15744796
TI  - Psychosocial treatment for opiate abuse and dependence.
AB  - BACKGROUND: Substance dependence is a major social and public health problem;
      therefore it is a priority to develop effective treatments. The treatment of
      opioid dependence is complex. Previous Cochrane reviews have explored the
      efficacy of pharmacotherapy for opiate dependence. This current review focuses on
      the role of psychosocial interventions alone for the treatment of opiate
      dependence. There are many different psychosocial interventions offered to opiate
      addicts, which are widely spread. There is some evidence for the effectiveness of
      psychosocial interventions, but no systematic review has even been carried out.
      OBJECTIVES: To assess the efficacy and acceptability of psychosocial
      interventions alone for treating opiate use disorders. SEARCH STRATEGY:
      Electronic searches of Cochrane Library, EMBASE, MEDLINE, and LILACS; reference
      searching; personal communication; conference abstracts; unpublished trials; book
      chapters on treatment of opioid abuse/ dependence. SELECTION CRITERIA: The
      inclusion criteria for all randomised-controlled trials were that they should
      focus on psychosocial interventions alone for treating opioid use disorders. DATA
      COLLECTION AND ANALYSIS: Reviewers extracted the data independently using
      relative risks, weighted mean difference and number needed to treat estimated,
      when possible. The reviewers assumed that people who died or dropped out had no
      improvement (intention to treat analysis) and tested the sensitivity of the final
      results to this assumption. MAIN RESULTS: Five studies fit the study criteria.
      These analysed Contingency Management, Brief Reinforcement Based Intensive
      Outpatient Therapy coupled with Contingency Management, Cue Exposure therapy,
      Alternative Program for Methadone Maintenance Treatment Program Drop-outs (MMTP)
      and Enhanced Outreach-Counselling Program. All the treatments were studied
      against the control (standard) treatment; therefore it was not possible to
      identify which type of psychosocial therapy was most effective. The main findings
      were that both Enhanced Outreach Counselling and Brief Reinforcement Based
      Intensive Outpatient Therapy coupled with Contingency Management had
      significantly better outcomes than standard therapy within treatment. This was
      regarding relapse to opioid use, re-enrollment in treatment and retention in
      treatment. At 1-month and 3- month follow up the effects of Reinforcement Based
      Intensive Outpatient Therapy were not sustained. There was no further follow up
      of the Enhanced Outreach Counselling group. The Alternative Program for MMTP Drop
      outs and the behavioural therapies of Cue Exposure and Contingency Management
      alone were no better than the control (standard) therapy. As the studies were
      heterogeneous, it was not possible to pool the results and perform a meta
      analysis. AUTHORS' CONCLUSIONS: The available evidence has low numbers and is
      heterogeneous. At present psychosocial treatments alone are not adequately proved
      treatment modalities or superior to any other type of treatment. It is important
      to develop a better evidence base for psychosocial interventions to assist in
      future rationale planning of opioid use drug treatment services. Large-scale
      randomised trials are required with longer follow up stating methods of
      randomisation, allocation concealment and blinding. Where possible this should
      include intention to treat analysis, with power calculations performed prior to
      the trial. These studies can be designed and delivered to provide usable data for
      better understanding of this important component of intervention in the field of
      dependence.

PMID- 15744798
TI  - Attaining exponential convergence for the flux error with second- and fourth
      order accurate finite-difference equations. II. Application to systems comprising
      first-order chemical reactions.
AB  - This article demonstrates that exponential convergence of the flux error can be
      achieved for any kinetic-diffusion system comprising an arbitrary number of
      (pseudo) first-order chemical reactions if the underlying PDEs are discretized as
      outlined for the box 2 or box 4 method in the preceding part of this article. By
      investigating the eigenvalues and eigenvectors of the first-order kinetic
      coupling matrix in general form the present article demonstrates that the
      simulation of any multispecies first-order kinetic diffusion system can be as
      accurately done as the simulation of a single representative one-species system.
      The Fourier coefficients governing the error level of the flux are much smaller
      in the limiting case of kinetic control as those reported in the preceding
      article for the limiting case of diffusion control. The higher rate of
      exponential convergence predicted on the basis of the mathematical model has been
      fully verified by the numerical results.

PMID- 15744799
TI  - Unilateral breast edema: spectrum of etiologies and imaging appearances.
AB  - Breast edema is defined as a mammographic pattern of skin thickening, increased
      parenchymal density, and interstitial marking. It can be caused by benign or
      malignant diseases, as a result of a tumor in the dermal lymphatics of the
      breast, lymphatic congestion caused by breast, lymphatic drainage obstruction, or
      by congestive heart failure. Here we describe several conditions, that cause
      unilateral breast edema with the aim of familiarizing radiologists with these
      disease entities.

PMID- 15744800
TI  - Development of a clinical protocol for home hospice care for Koreans.
AB  - As the Korean government's recognition of the importance of hospice service
      grows, the government has initiated a variety of hospice services in Korea. Each
      hospice organization has shown a significant difference in its health care
      delivery methods, constitution and care content. Developing a clinical protocol
      is essential for establishing standardized hospice services. A preliminary
      protocol was drawn up by examining the records of terminal patients (n=541) in a
      home hospice organization while elucidating the health problems as well as
      classifying them through the Home Health Care Classification (HHCC), and by
      reviewing the relevant nursing interventions and medical treatments in the
      literature concerning the clinical protocols. Korea's leading hospice specialty
      groups participated in four rounds of content validity verification processes in
      order to establish a protocol. A guideline was developed through a team approach,
      integrating the opinions of doctors, nurses, ministers, volunteers, patients'
      families, nutritionists and pharmacists. Eighteen health problems and a total of
      223 interventions (173 major treatments and nursing interventions, and 50
      optional interventions) were included in the final clinical protocol. This study
      is expected to contribute to the overall qualitative improvement of home hospice
      care and the subsequent shortening of documentation time. Evaluation tools and a
      regulatory feedback system need to be developed in order to maintain consistent
      evaluation procedures based on the continuous promotion and use of the protocol.

PMID- 15744801
TI  - Prealbumin is not sensitive indicator of nutrition and prognosis in critical ill
      patients.
AB  - It was reported that 30-50% of inpatients are in a malnutrition status. Measuring
      the prealbumin level is a sensitive and cost-effective method for assessing the
      severity of illness in critically or chronically ill patients. However it is
      uncertain whether or not the prealbumin level correlates with the level of
      nutrition support and outcomes in critically ill patients. The aim of this study
      was to evaluate serum prealbumin level as an indicator of the effectiveness of
      nutrition support and the prognosis in critically ill patients. Forty-four
      patients who received total parenteral nutrition for more than 7 days at an
      intensive care unit (ICU) were studied. The serum prealbumin was measured at the
      initial time of nutrition support and at the almost seventh day since the first
      measurement. The patients were allocated into two groups. In Group 1 (n=31) and 2
      (n=13), the prealbumin level increased and decreased, respectively. Age, APACHE
      II score, nutrition status, nutritional requirement and amount of supply,
      mortality, hospital day and ICU day in the two groups were compared. The serum
      prealbumin level increased in 31 out of the 44 patients. The average calorie
      intake was 1334 Kcal/day (83% of energy requirement) in Group 1 and 1170 kcal/day
      (76% of energy requirement) in Group 2 (p=0.131). The mortality was 42% in Group
      1 and 54% in Group 2 (p=0.673). The average hospital day/ ICU day in Groups 1 and
      2 were 80 days/38 days and 60 days/31 days respectively. In conclusion, in
      critically ill patients, the serum prealbumin level did not respond sensitively
      to nutritional support. In addition an increase in the prealbumin level dose not
      indicate a better prognosis for critically ill patients.

PMID- 15744802
TI  - Prognostic factors of status epilepticus in children.
AB  - We retrospectively reviewed the medical records of 189 children who were admitted
      to the Pediatric Neurology Department at Yonsei University College of Medicine
      with status epilepticus (SE) between April, 1994 and April, 2003. The children
      were followed up for a mean duration of 17 months. We analyzed the clinical
      findings and the relationships between neurologic sequelae, recurrence, age of
      onset, presumptive causes, types of seizure, seizure duration and the presence of
      fever. Mean age at SE onset was 37 months. Incidences by seizure type
      classification were generalized convulsive SE in 73.5%, and non-convulsive SE in
      26.5%. The incidences of presumptive causes of SE were idiopathic 40.7%, epilepsy
      29.1%, remote 16.4% and acute symptomatic in 13.3%. Among all the patients,
      febrile episodes occurred in 35.4%, especially in patients under 3 year old, and
      38.4% of these were associated with febrile illness regardless of presumptive
      cause. Neurologic sequelae occurred in 33% and the mortality rate was 3%.
      Neurologic sequelae were lower in patients that presented with an idiopathic
      etiology and higher in generalized convulsive SE patients. The recurrence of SE
      was higher in patients with a remote symptomatic epileptic etiology, and
      generalized convulsive SE showed higher rates of recurrence. Based on this
      retrospective study, the neurologic outcomes and recurrence of SE were found to
      be strongly associated with etiology and seizure type. Age, seizure duration and
      the presence of febrile illness were found to have no effect on outcome.

PMID- 15744803
TI  - Effects of methylphenidate on quantitative EEG of boys with attention-deficit
      hyperactivity disorder in continuous performance test.
AB  - The purpose of this study was to investigate the effects of methylphenidate, a
      psychostimulant, on quantitative electroencephalography (QEEG) during the
      continuous performance test (CPT) in boys with attention-deficit hyperactivity
      disorder (ADHD). The QEEG was obtained from 20 boys with ADHD. The amplitudes of
      4 bands (alpha, beta, delta, and theta) in the QEEG, as well as the theta /beta
      ratio, before and after the administration of methylphenidate were compared
      during both the resting and CPT states. Methylphenidate induced a significant
      increase of alpha activities in both the right and left frontal and occipital
      areas, an increase of beta activities in almost all areas except for the temporal
      region, a decrease of theta activities in both the occipital and right temporo
      parietal areas, a mild decrease of delta activities in the occipito-parietal
      areas, and an increase of the theta/beta ratio in the right frontal and parieto
      occipital, and left temporal areas during the CPT state. No significant QEEG
      changes were induced by the administration of methylphenidate in the resting
      state. These data suggest that methylphenidate has greater electrophysiological
      influences on the cerebral topographical activities during the performance of
      attentional tasks, as compared to the resting state, in boys with ADHD.

PMID- 15744804
TI  - Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus.
AB  - Insulin resistance, which implies impairment of insulin signaling in the target
      tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important
      role in insulin resistance through the dysregulated production and secretion of
      adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen
      activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin.
      Adiponectin was estimated to be a protective adipocytokine against
      atherosclerosis, and also to have an anti-inflammatory effect. In this study, the
      relationship between fasting plasma adiponectin concentration and adiposity, body
      composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting
      insulin concentration were examined in Korean type 2 diabetes. The difference in
      the adiponectin concentrations was also examined in diabetic and non-diabetic
      subjects, with adjustment for gender, age and body mass index. 102 type 2
      diabetics and 50 controls were examined. After a 12-h overnight fast, all
      subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples
      were drawn for the determinations of fasting plasma glucose, insulin,
      adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL
      cholesterol. The body composition was estimated using a bioelectric impedance
      analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin
      tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the
      fasting adiponectin concentrations were significantly lower in men than in women.
      They were negatively correlated with BMI (r=-0.453), hip circumference (r=
      0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In
      addition, they were positively correlated with systolic blood pressure (r=0.321)
      and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol
      were found to be independent variables, from a multiple logistic regression
      analysis, which influenced the adiponectin concentration. Compared with the non
      diabetic group, the adiponectin concentrations were significantly lower in the
      diabetic group, with the exception of obese males. In conclusion, the plasma
      adiponectin concentrations were closely related to the insulin resistance
      parameters in Korean type 2 diabetic patients.

PMID- 15744805
TI  - Therapeutic effects of Holmium-166 chitosan complex in rat brain tumor model.
AB  - This study examined the effectiveness of Holmium-166 (Ho-166) chitosan complex
      therapy for a malignant glioma. Cultured C6 glioma cells (100,000 in 5 microl)
      were injected into the caudate/putamen of 200-250 gram Wistar rats. Five days
      later, a Ho-166 chitosan complex was injected into the same site of the glioma
      injection. Four injection doses were administered: the control group received PBS
      10 microl, group 1 received an injection of 100 microCi (10 microl), group 2
      received an injection of 50 microCi (5 microl), and group 3 received an injection
      of 10 microCi (1 microl). The average tumor volume for each group was 1.385 mm3
      for the control group, 0.036 mm3 for group 1, 0.104 mm3 for group 2, and 0.111
      mm3 for group 3. Compared with the control group, the size of the tumors in
      groups 1, 2 and 3 was reduced by an average of 97.4%, 92.5% and 91.9%,
      respectively. The Kaplan-Meier survival curve of group 2 was the longest,
      followed by groups 3, group 1 and the control. The mean survival was 22.8, 59,
      60, and 44.6 days for the control group and groups 3, 2 and 1, respectively. H-E
      staining revealed that group 2 yielded the best results in the destruction of the
      malignant glioma. TUNEL staining and immunohistochemical studies indicated
      apoptotic features. The Ho-166 chitosan complex proved to be effective in
      destroying the malignant glioma.

PMID- 15744806
TI  - The diagnostic value of endoprobe for small esophageal leiomyomas derived from
      the muscularis mucosae.
AB  - Esophageal leiomyoma derived from the muscularis mucosae (MM) is a rare
      condition, and the optimal modality for diagnosis and treatment is controversial.
      Endoscopic ultrasonography can provide an accurate image of esophageal layer
      structure, providing information on lesion suitability for potential endoscopic
      therapy. We attempted to investigate the diagnostic value of a transendoscopic
      balloon-tipped miniature ultrasonic endoprobe for small esophageal leiomyomas
      derived from MM. We resected 7 small esophageal leiomyomas derived from MM by
      endoscopic mucosal resection (EMR), all of which were diagnosed by a balloon
      tipped endoprobe. The endosonographic and pathologic features of 7 cases of small
      esophageal leiomyomas derived from MM were compared. The balloon-tipped endoprobe
      clearly showed all 7 small esophageal leiomyomas derived from MM, even those
      under 5 mm in size (smallest lesion, 3.0 mm). The endosonographic characteristics
      of small esophageal leiomyomas derived from MM were a hypoechoic mass with
      smooth, regular, and a well-defined outer margin and homogenous inner echogram
      arising from the second hypoechoic layer. Complete resections were possible in
      all 7 cases by EMR without any complications. Tumor size was 3.0-13.5 mm (mean
      7.8 mm) in maximum diameter. In all cases, endosonographic findings by endoprobe
      were exactly concordant with pathologic finding in determining the tumors depth
      in the esophageal wall, tissue origin and characteristics, growth pattern, and
      size. We detail the balloon-tipped endoprobe is a simple, convenient, and very
      useful in making accurate diagnosis of small esophageal leiomyomas derived from
      the MM and the appropriate applications of EMR.

PMID- 15744807
TI  - Perioperative anticoagulation in patients with mechanical heart valves undergoing
      elective surgery: results of a survey conducted among Korean physicians.
AB  - The optimal perioperative anticoagulation management in patients on warfarin
      therapy is poorly defined due to the lack of randomized trials. Because
      guidelines are heterogeneous, it was hypothesized that "treatment strategies are
      not uniform in clinical practice". Between February 2003 and May 2003, a
      questionnaire with 4 different clinical scenarios was distributed to physicians
      by e-mail, or direct contact was made by a survey monitor. Two scenarios
      described the cases of patients with a mechanical heart valve (MHV) in the mitral
      position, with additional risk factors for a systemic embolism; one undergoing
      major (scenario 1) and the other minor surgery (scenario 3). Two scenarios
      described patients with an aortic MHV; one undergoing major (scenario 2) and the
      other minor (scenario 4) surgery. Different preoperative and postoperative
      management options were offered. The treatment options for all scenarios were the
      same. Of the 90 questionnaires distributed, 52 (57.8%) were returned.
      Hospitalization for full-dose intravenous unfractionated heparin (IV UH) was the
      most commonly selected strategy in the preoperative phase for scenarios 1 (59%),
      2 (42%) and 3 (44%). In scenario 4, 34% chose IV UH. Outpatient, full- dose,
      subcutaneous UH or low-molecular-weight heparin (LMWH) was the most selected
      option in the postoperative phase for all scenarios, with the exception of number
      4 (52.9% in scenario 1, 34% in scenario 2, 32%, in scenario 3 and 28% in scenario
      4). Even among expert clinicians, the management of perioperative anticoagulation
      is heterogeneous. In particular, the definition of risk categories and the
      optimal intensity of antithrombotic drugs need to be defined by well-designed
      prospective studies.

PMID- 15744808
TI  - Serial assessment of myocardial properties using cyclic variation of integrated
      backscatter in an adriamycin-induced cardiomyopathy rat model.
AB  - Although adriamycin (Doxorubicin) is one of the most effective and useful
      antineoplastic agents for the treatment of a variety of malignancies, its
      repeated administration can induce irreversible myocardial damage and resultant
      heart failure. Currently, no marker to detect early cardiac damage is available.
      The purpose of this study was to investigate whether an assessment of the
      acoustic properties of the myocardium could enable the earlier detection of
      myocardial damage after adriamycin chemotherapy. Forty Wistar rats were treated
      with adriamycin (2 mg/kg, i.v.) once a week for 2, 4, 6 or 8 weeks consecutively.
      Left ventricular ejection fraction (LVEF) was calculated using M-mode
      echocardiography data. The magnitude of cardiac cycle dependent variation of
      integrated backscatter (CVIB) of the myocardium was measured in the mid segment
      of the septum and in the posterior wall of the left ventricle, using a real time
      two dimensional integrated backscatter imaging system. LVEF was significantly
      lower in the adriamycin-treated 8-week group than in the controls (75+/-9 vs 57+/
      8%, p<0.05). Myocyte damage was only seen in the 8-week adriamycin-treated group.
      However, no significant changes of CVIB were observed between baseline or during
      follow-up in the ADR or control group. In conclusion, serial assessment of the
      acoustic properties of the myocardium may not be an optimal tool for the early
      detection of myocardial damage after doxorubicin chemotherapy in a rat model.

PMID- 15744809
TI  - Serum levels of advanced glycation end products are associated with in-stent
      restenosis in diabetic patients.
AB  - The formation of advanced glycation end products (AGEs), in various tissues has
      been known to enhance immunoinflammatory reactions and local oxidant stresses in
      long standing diabetes. Recently, AGEs have been reported to play a role in
      neointimal formation in animal models of arterial injury. We attempted to
      determine whether the serum levels of AGEs are associated with coronary
      restenosis in diabetic patients. Blood samples were collected from diabetic
      patients with coronary artery disease undergoing stent implantation and the serum
      levels of AGEs were analyzed by the fluorescent intensity method. The development
      of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary
      angiography. A total of 263 target lesions were evaluated, in 203 patients. The
      ISR rate in the high-AGE (>170 U/ml) group (40.1%) was significantly higher than
      in the low-AGE group (<or=170 U/ml) (19.6%) (p<0.001). Furthermore, multivariate
      analysis revealed that a high level of serum AGEs is an independent risk factor
      for the development of ISR (odds ratio, 2.659; 95% CI, 1.431-4.940; p=0.002). The
      serum levels of AGEs constitute an excellent predictive factor for ISR, and
      should be one of the guidelines for medical therapy and interventional strategy
      to prevent ISR in diabetic patients.

PMID- 15744810
TI  - The utility of multi-detector row spiral CT for detection of coronary artery
      stenoses.
AB  - Contrast-enhanced multi-detector row spiral computed tomography (MDCT) was
      introduced as a promising noninvasive method for vascular imaging. This study
      examined the accuracy of this technique for detecting significant coronary artery
      stenoses. Both MDCT(Sensation 16, Siemens, Germany, 12x0.75 mm collimation and
      0.42 sec rotation speed, 120 kV, 500 effective mA, and 2.7 mm/rotation table
      feed) and invasive coronary angiography (CAG) were performed on 61 patients (mean
      age 59.2+/-10, 44 men) who were suspected of having coronary artery disease. All
      patients were treated with atenolol (25-50 mg) prior to imaging and the heart
      rate was maintained below 65 beats per minutes during image acquisition. The
      images were reconstructed in the diastole around TI-400 ms with a 0.5 mm
      increment and a 1.0 mm thickness. All coronary arteries with a diameter of 2.0 mm
      or more were assessed for the presence of a stenosis (>50% luminal narrowing).
      Two independent radiologists who were unaware of the results of the invasive CAG
      evaluated the MDCT data, and the results were compared with those from the
      invasive CAG (interval 1-27, mean 11 days). An evaluation of the CT coronary
      angiogram (CTCA) was possible in 58 of the 61 patients (95%). Image acquisition
      of the major coronary arteries including the left main trunk was available in 229
      out of 244 arteries. Invasive CAG showed that 35 out of 58 patients had
      significant coronary artery stenoses by. patient analysis of those who could be
      evaluated showed that CT coronary angiography correctly classified 30 out of 35
      patients as having at least 1 coronary stenosis (sensitivity 85.7%, specificity
      91.3%, positive predictive value 93.8%, negative predictive value 80.8%). By
      analyzing each coronary artery, CAG found 62 stenotic coronary arteries in the
      229 coronary arteries that could be evaluated. MDCT correctly detected 50 out of
      62 stenotic coronary arteries and an absence of stenosis was correctly identified
      in 156 out of 167 normal coronary arteries (sensitivity 80.6%, specificity 93.4%,
      positive predictive value 81.9%, negative predictive value 92.8%). The non
      invasive technique of MDCT for examining the coronary artery appears to be a
      useful method for detecting coronary artery stenoses with a high accuracy
      particularly with the proximal portion and large arteries.

PMID- 15744811
TI  - Comparison of unmonochromatized synchrotron radiation and conventional X-rays in
      the imaging of mammographic phantom and human breast specimens: a preliminary
      result.
AB  - A simple imaging setup based on the principle of coherence-based contrast X-ray
      imaging with unmonochromatized synchrotron radiation was used for studying
      mammographic phantom and human breast specimens. The use of unmonochromatized
      synchrotron radiation simplifies the instrumentation, decreases the cost and
      makes the procedure simpler and potentially more suitable for clinical
      applications. The imaging systems consisted of changeable silicon wafer
      attenuators, a tungsten slit system, a CdWO4 scintillator screen, a CCD (Charge
      Coupled Device) camera coupled to optical magnification lenses, and a personal
      computer. In preliminary studies, a spatial resolution test pattern and glass
      capillary filled with air bubbles were imaged to evaluate the resOolution
      characteristics and coherence-based contrast enhancement. Both the spatial
      resolution and image quality of the proposed system were compared with those of a
      conventional mammography system in order to establish the characteristic
      advantages of this approach. The images obtained with the proposed system showed
      a resolution of at least 25 microm on the test pattern with much better contrast,
      while the images of the capillary filled with air bubbles revealed coherence
      based edge enhancement. This result shows that the coherence-based contrast
      imaging system, which emphasizes the refraction effect from the edge of materials
      of different refractive indexes, is applicable to imaging studies in fundamental
      medicine and biology, although further research works will be required before it
      can be used for clinical applications.

PMID- 15744813
TI  - A comparison of different pelvic reconstruction surgeries using mesh for pelvic
      organ prolapse patients.
AB  - This study was carried out in order to compare the effects in different surgeries
      using mesh in pelvic organ prolapse patients whose leading points were C. Thirty
      nine patients were categorized into 3 groups: group A pelvic reconstruction with
      hysterectomy; group B hysterectomy prior to pelvic reconstruction; and group C
      pelvic reconstruction with uterus preserved. At first visit, POP-Q stage was
      determined, and age, BMI, admission days, operation time, post-operative stage
      and complications were observed and results were analyzed and compared. All
      patients who were operated upon converted to stage one month following the
      operation, and no further change was observed except in one patient. Group
      admission days were not significantly different, but tended to be lower in group
      C. Group average operation times between 'group A and B' and 'group A and C' were
      statistically different. No significant difference was observed in post-operative
      complications between the groups, but 3 members of group A developed erosion,
      whereas no erosion occurred in groups B and C. Pelvic reconstruction using mesh
      is a highly efficient method of treating pelvic organ prolapse. Improvements in
      stage and post-operative complications were not significantly different in the
      groups. However, uteropexy showed a shorter operation time, fewer admission days,
      and less erosion due to mesh than conventional pelvic reconstruction with
      hysterectomy.

PMID- 15744812
TI  - Clinical characteristics of dialysis related sclerosing encapsulating
      peritonitis: multi-center experience in Korea.
AB  - Sclerosing encapsulating peritonitis (SEP) is a rare but serious complication in
      patients with continuous ambulatory peritoneal dialysis (CAPD), and is
      characterized by a progressive, intra-abdominal, inflammatory process resulting
      in the formation of sheets of new fibrous tissue, which cover, bind, and
      constrict the viscera, thereby compromising the motility of the bowel. No
      satisfactory estimate is available on the comparative incidence of dialysis
      related SEP and the pathogenesis of SEP still remains uncertain. Although recent
      therapeutic approaches have reported varying degrees of success, an efficient
      measure to detect, at an early stage, patients at risk for SEP would be
      beneficial and a standardized treatment regimen to prevent the illness is
      urgently needed. This study aimed to evaluate the clinical features of SEP and to
      identify the possible risk factors for the development of SEP in CAPD patients.
      We retrospectively reviewed by questionnaire SEP cases among CAPD patients from 7
      university hospital dialysis centers in Korea, including Yonsei University, Ajou
      University, Catholic University, Inha University, Kyungpook University, Seoul
      National University and Soonchunhyang University, from January 1981 to December
      2002. Out of a total of 4,290 CAPD patients in these centers, 34 cases developed
      SEP with an overall prevalence of 0.79%. The male to female ratio was 17:17. The
      median age of these patients was 44.5 years (range 19-66). The median duration of
      CAPD before SEP was 64 months (9-144) and 68% of patients (23/34) had been on
      CAPD for more than 4 years. Peritonitis (including two fungal cases) was the main
      cause of catheter removal in SEP (27 cases, 79%). Seventy-five percent of the
      cases (15/20) were administered beta-blocker for a mean duration of 85 months (26
      130). Among 10 cases with available peritoneal equilibration test (PET) data, 8
      showed high transporter characteristics, and the remaining 2 were high average.
      Eighteen cases were diagnosed by clinical and radiologic methods, and 16 were
      surgically diagnosed. Eleven cases were surgically treated and the others were
      treated conservatively with intermittent total parenteral nutrition (TPN). The
      overall mortality rate was 24%. SEP is a serious, life threatening complication
      of CAPD. Most cases had a PD duration of more than 4 years, a history of severe
      peritonitis, and high transporter characteristics in PET. Therefore, to reduce
      the incidence of SEP, careful monitoring and treatment, including early catheter
      removal in patients with severe peritonitis, should be considered for long-term
      CAPD patients with the above characteristics.

PMID- 15744814
TI  - Tumor volume change after chemotheraphy as a predictive factor of disease free
      survival for osteosarcoma.
AB  - Change in tumor volume after chemotherapy appears to have a prognostic
      significance for the outcome of osteosarcoma. A newly developed volume
      measurement method based on three-dimensional summation with a proved
      reproducibility was utilized to measure osteosarcoma tumor volume. This
      retrospective analysis included 38 patients with biopsy- proven, nonsurface,
      skeletal high-grade osteosarcoma. The treatment was started by using three cycles
      of preoperative chemotherapy with cisplastin (100 mg/m2) and adriamycin (30
      mg/m2). The tumor volume was measured before and after preoperative chemotherapy
      using three-dimensional magnetic resonance image measurement. The percentage of
      tumor necrosis was assessed by pathologic exam. After three cycle of
      postoperative chemotherapy, the patients were followed up at regular interval.
      For the 23 good responder patients, the mean survival time was 73.2 months (95%
      confidence interval 61.9-84.5 months), and for the 15 poor responder patients,
      the mean survival time was 50.8 months (95% confidence interval 38.6-63.1 months)
      (p<0.05). For the 14 patients with increased tumor volume after chemotherapy, the
      mean survival time was 47.5 months (range: 36.3-58.6 months) and for the 24
      patients with stable or decreased tumor volume, the mean survival time was 74.3
      months (range: 63.79-84.88 months) (p<0.05). Among the various factors,
      histopathologic response and tumor volume change after chemotherapy predicted
      disease free survival (p<0.05). Change in the tumor volume that was measured with
      a reproducible method and the histopathologic response after chemotherapy were
      the important predictors of disease free survival for osteosarcoma patients.

PMID- 15744815
TI  - Surgical treatments for lumbar disc disease in adolescent patients;
      chemonucleolysis / microsurgical discectomy/ PLIF with cages.
AB  - The herniated lumbar disc (HLD) in adolescent patients is characterized by
      typical discogenic pain that originates from a soft herniated disc. It is
      frequently related to back trauma, and sometimes it is also combined with a
      degenerative process and a bony spur such as posterior Schmorl's node.
      Chemonucleolysis is an excellent minimally invasive treatment having these
      criteria: leg pain rather than back pain, severe limitation on the straight leg
      raising test (SLRT), and soft disc protrusion on computed tomography (CT).
      Microsurgical discectomy is useful in the cases of extruded or sequestered HLD
      and lateral recess stenosis due to bony spur because the nerve root is not
      decompressed with chymopapain. Spinal fusion, like as PLIF, should be considered
      in the cases of severe disc degeneration, instability, and stenosis due to
      posterior central bony spur. In our study, 185 adolescent patients, whose follow
      up period was more than 1 year (the range was 1-4 years), underwent spinal
      surgery due to HLD from March, 1998 to December, 2002 at our institute. Among
      these cases, we performed chemonucleolysis in 65 cases, microsurgical discectomy
      in 94 cases, and posterior lumbar interbody fusion (PLIF) with cages in 33 cases
      including 7 reoperation cases. The clinical success rate was 91% for
      chemonucleolysis, 95% for microsurgical disectomy, and 89% for PLIF with cages,
      and there were no non- union cases for the PLIF patients with cages. In
      adolescent HLD, chemonucleolysis was the 1st choice of treatment because the soft
      adolescent HLD was effectively treated with chemonucleolysis, especially when the
      patient satisfied the chemonucleolysis indications.

PMID- 15744816
TI  - Cyclooxygenase-2 and p53 expression as prognostic indicators in conventional
      renal cell carcinoma.
AB  - The aim of this study was to investigate the relationship of cyclooxygenase (COX)
      2 and p53 expression with prognosis in patients with conventional renal cell
      carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of
      conventional RCC from 92 patients, who had undergone radical nephrectomy, were
      examined for COX-2 and p53 expression by immunohistochemistry and compared with
      clinicopathological variables. The COX-2 expression significantly correlated only
      with tumor size (p=0.049), whereas the p53 expression profoundly correlated with
      the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or
      metachronous; p=0.004). The COX-2 overexpression did not significantly associate
      with p53 positivity (p=0.821). The survival rate of patients correlated with the
      p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506).
      Multivariate analyses indicated that tumor size, M stage, and p53 expression were
      independent prognostic factors for cancer-specific survival. The COX-2 expression
      was not an independent factor. These results show that the increased expression
      of p53 was associated with metastasis and a worse prognosis in conventional RCC,
      which suggests that p53 might have played an important role in the progression of
      conventional RCC. The increased expression of COX-2 was associated only with
      tumor size, but may not be an important prognostic factor in conventional RCC. No
      association was observed between COX-2 overexpression and p53 positivity in
      conventional RCC.

PMID- 15744817
TI  - Impact of cyclosporin on podocyte ZO-1 expression in puromycin aminonucleoside
      nephrosis rats.
AB  - Puromycin aminonucleoside (PAN)-induced nephrosis is a well-described model of
      human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not
      completely understood. To investigate whether proteinuria in the PAN model is
      associated with an alteration of zonula occludens-1 (ZO-1) expression within the
      glomeruli, and whether cyclosporin A (CsA) has an effect on proteinuria and ZO-1
      expression in this model, eighteen Sprague Dawley (SD) rats were assigned into
      three groups. Twelve rats received a single intraperitoneal injection of PAN (15
      mg/100 g). The other six rats received an equal volume of saline (normal control
      group; control). CsA solution was administered intraperitoneally once a day for
      20 days after the PAN injection (n=6, PAN+CsA). The remaining six rats received
      PAN, but they didn't receive CsA (n=6, PAN). Compared to control rats (35.1+/-5.4
      mg/day), the 24-hour urinary protein excretion on day 18 was significantly higher
      in the PAN rats (1021.9+/-128.9 mg/day, p<0.01), and the CsA treatment partly
      reversed the increase in proteinuria in the PAN rats (556.4+/-102.3 mg/day,
      p<0.05). Glomerular ZO-1 protein expressions were significantly increased in the
      PAN rats as compared to the control group on day 20 (176%, p<0.01). CsA treatment
      for 20 days in the PAN rats inhibited the increase in ZO-1 protein expression by
      71.1% (p<0.05). CsA treatment significantly diminished the glomerular ZO-1
      expression in the PAN rats as assessed by immunohistochemistry. CsA treatment
      significantly reduced proteinuria and the diminished glomerular ZO-1 expression
      in a PAN nephrosis rat model. These findings suggest the potential role of the
      slit diaphragm associated proteins in the development of the nephrotic syndrome,
      and CsA decreased the proteinuria probably by a direct action on the expression
      of these proteins in podocytes. Further investigations are needed to clarify the
      role of slit diaphragm associated proteins in the development of PAN nephrosis.

PMID- 15744818
TI  - Rolipram, a phosphodiesterase 4 inhibitor, stimulates inducible cAMP early
      repressor expression in osteoblasts.
AB  - Phosphodiesterase (PDE) 4 inhibitors have been shown to induce the cAMP-mediated
      signaling pathway by inhibiting cAMP hydrolysis. This study investigated the
      effect of a PDE4 inhibitor on the expression of the inducible cAMP early
      repressor (ICER), which is an endogenous inhibitor of CRE- mediated
      transcription, in osteoblastic cells. RT-PCR analysis revealed that rolipram, a
      PDE4 inhibitor, stimulates the ICER mRNA in a dose dependent manner. The
      induction of ICER mRNA expression by rolipram was suppressed by the inhibitors of
      protein kinase A (PKA) and p38 MAPK, suggesting the involvement of PKA and p38
      MAPK activation in ICER expression by rolipram. It was previously shown that
      rolipram induced the expression of TNF-related activation-induced cytokine
      (TRANCE, also known as RANKL, ODF, or OPGL) in osteoblasts. This paper provides
      evidences that a transcriptional repressor like ICER might modulate TRANCE mRNA
      expression by rolipram in osteoblasts.

PMID- 15744819
TI  - Warty squamous cell carcinoma of the vulva in older women: association with human
      papillomavirus.
AB  - Warty squamous cell carcinoma (WSCC), a rare variant of squamous cell carcinoma
      occurring in younger women, is primarily associated with human papillomavirus
      (HPV) infection. Although WSCC appears to exhibit less aggressive behavior than
      typical well-differentiated squamous cell carcinoma, it bears the risk of
      regional metastasis. Accordingly, WSCC should be differentiated from other
      verruciform neoplasms. We describe a rare case of WSCC with a short disease
      duration occurring in a woman of old age. We found the presence of HPV DNA
      different from other well-known types of high risk and low risk HPV by DNA chip
      microarray. These results suggest that various types of HPV can be associated
      with the pathogenesis of WSCC.

PMID- 15744820
TI  - Meningitis due to bacillus anthracis.
AB  - The first case of haemorrhagic meningitis due to Bacillus anthracis in the
      European part of Turkey is reported here. B. anthracis, sensitive to penicillin,
      was isolated from the cerebrospinal fluid and blood cultures. Although
      appropriate therapy was administered, the patient died two days after
      hospitalization.

PMID- 15744821
TI  - A case of tympanogenic labyrinthitis complicated by acute otitis media.
AB  - Widespread use of antimicrobial drugs in the management of otitis media has
      significantly reduced the incidence of labyrinthitis nowadays. Cases of
      tympanogenic labyrinthitis following acute otitis media have rarely been reported
      in recent literature on otolaryngology. We report an unusual case of tympanogenic
      labyrinthitis that presented with sudden sensorineural hearing loss (SNHL)
      following acute otitis media in an adult who had no previous otological
      complaints. An audiogram revealed SNHL with pure tone threshold of 43.7 dB in the
      left ear. MRI was helpful to identify the inflammatory change of the membranous
      labyrinth. The patient's hearing returned to normal after treatment. The definite
      diagnosis of serous labyrinthitis was established retrospectively.

PMID- 15744822
TI  - Broken guidewire fragment in the radio-brachial artery during transradial sheath
      placement: percutaneous retrieval via femoral approach.
AB  - A case in which a 0.014" wire was broken during the sheath placement in the
      radial artery for transradial coronary procedure is described here, and a
      successful retrieval of it using conventional methods is also described. Through
      the left femoral artery, the 6 Fr guiding catheter was advanced down to the tip
      of the broken wire at the brachial artery, and the distal part of the broken
      guidewire was captivated into the guiding catheter. By inflating the balloon
      catheter inside of the guiding catheter, seized broken guidewire between the
      inflated balloon and the guiding catheter was removed successfully by withdrawing
      the whole system en bloc.

PMID- 15744823
TI  - Symmetric lipofibromatous hamartoma affecting digital nerves.
AB  - Lipofibromatous hamartoma of the nerve is a benign tumor, which affects the major
      nerves and their branches in the human body. It is often found in the median
      nerve of the hand and is commonly associated with macrodactyly, but it is rarely
      found in the digital nerves at the peripheral level. This tumor is often found in
      young adults and may go through a self- limiting course. However, operation is
      indicated when the tumor size is large or when the associated nerve compressive
      symptoms are present. We have experienced a rare case of lipofibromatous
      hamartoma that symmetrically involved the volar digital nerves of both index
      fingers on the ulnar side. With the aid of a microscope, we dissected and removed
      the tumor as much as possible without sacrificing the nerve. No sensory change
      occurred in both fingers and no sign of recurrence was observed upon follow-up.

PMID- 15744824
TI  - A case of pulmonary cryptococcosis with non-small cell lung cancer in idiopathic
      CD4+ T-lymphocytopenia.
AB  - Cryptococcus neoformans commonly causes opportunistic infections in
      immunocompromised patients, especially in patients with AIDS. CD4+ T
      lymphocytopenia in AIDS indicates an increased risk of opportunistic infection
      and a decline in immunological function. Idiopathic CD4 T-lymphocytopenia (ICL)
      is characterized by depletions in the CD4+ T-cell subsets, without evidence of
      HIV infection. Immunodeficiency can exist in the absence of laboratory evidence
      of HIV infection, and T-cell subsets should be evaluated in patients who present
      with unusual opportunistic infections. We report a case of pulmonary
      cryptococcosis and lung cancer in a patient with persistently low CD4+ cell
      counts, without evidence of HIV infection.

PMID- 15744825
TI  - Malignant fibrous histiocytoma of chest wall.
AB  - Primary malignant fibrous histiocytoma (MFH) of the chest wall is rare. We report
      a case of primary MFH arising from the chest wall, which was thought to be a
      metastasis or myeloma. The imaging study revealed a single mass of the chest wall
      involving a rib. Resection and chest wall reconstruction was done. The histologic
      diagnosis was storiform-pleomorphic primary MFH. Although MFH of the chest wall
      is an uncommon pathology, it should be considered in the differentiation of a
      single bony destructive lesion involving the rib with a soft tissue component.

PMID- 15744826
TI  - Metastasis of transitional cell carcinoma to the lower abdominal wall 20 years
      after cystectomy.
AB  - Iatrogenic implantation has been the main cause in the majority of cases of
      transitional call carcinoma (TCC) with metastasis to the abdominal wall. A 66
      year-old woman had undergone radical cystectomy 20 years prior to presenting.
      Radiological investigations revealed one mass in the left lower abdominal wall
      and one mass in the right inguinal area. She underwent wide excision of the
      lesions that revealed metastasis of TCC. This report describes this case of a
      woman with bladder carcinoma who developed a metastasis in the anterior abdominal
      wall following an apparent disease-free interval of 20 years.

PMID- 15744828
TI  - Asymptomatic tubular duplication of the transverse colon in an adult.
AB  - Colonic duplication is a rare congenital anomaly of the alimentary tract. In most
      cases, symptomatic duplications of the colon are recognized and treated by
      childhood. It is uncommon for these lesions to be detected in the adulthood since
      they present with vague symptoms if at all. We experienced a case of asymptomatic
      tubular duplication of the transverse colon in a 40-year-old female. Barium enema
      revealed a tubular duplication of the transverse colon. The duplicated segment
      arose from the mid ascending colon and incorporated just proximal to the splenic
      flexure, running parallel to the transverse colon and communicating with it at
      both ends. Colonoscopy demonstrated a normal colonic mucosa in the duplicated
      segment. The diameter of its lumen gradually narrowed proximally and the
      colonoscope could not be passed through the proximal opening of the segment. The
      patient did not need any treatment. Duplications of the alimentary tract can be
      found at any age. The possibility of congenital lesions in the adult population
      should not be overlooked.

PMID- 15744827
TI  - Littoral cell angioma (LCA) associated with liver cirrhosis.
AB  - A littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. A 60
      year-old man, with multiple nodules in imaging study and liver cirrhosis graded
      as Child-Pugh classification class A, was transferred for splenomegaly. A
      thrombocytopenia was found on hematological evaluation. Because there was no
      evidence of hematological and visceral malignancy, a splenectomy was performed
      for a definitive diagnosis. The histological and immunohistochemical features of
      the splenic specimens were consistent with a LCA. After the splenectomy, the
      thrombocytopenia recovered to the normal platelet count. There has been no
      previous report of a LCA combined with liver cirrhosis. Herein, the first case of
      a LCA in Korea, diagnosed and treated by a splenectomy, is reported.

PMID- 15744829
TI  - Novel contributions to the Asian CFTR mutation spectrum: Genotype and phenotype
      in Thai patients with cystic fibrosis.

PMID- 15744830
TI  - A novel mutation in the DIA1 gene in a patient with methemoglobinemia type II.

PMID- 15744831
TI  - New type of twin spot.

PMID- 15744832
TI  - [Radiological quiz of the month: a maxillary mass in an infant].

PMID- 15744833
TI  - 18O-labeling quantitative proteomics using an ion trap mass spectrometer.
AB  - We describe a method for simultaneous identification and quantitation of proteins
      within complex mixtures. The method consists of 18O-labeling, a simple stable
      isotope-coding that requires merely enzymatic digestion in 18O-water, in
      combination with a capillary-liquid chromatography electrospray ion-trap mass
      spectrometer. In a separate experiment using the same sample and a spike test, we
      demonstrate that the difference ration was calculated accurately using the 18O
      labeling method even if the protein was part of a complex mixture. Our data also
      suggest that the accuracy of the quantitation can be improved by averaging the
      difference ratios of several peptides. In comparing our method with the isotope
      coded affinity tag (ICAT) method, we show that the 18O-labeling method has the
      advantages of better recovery and fewer isotope effects. Therefore, the 18O
      labeling method is a powerful tool for large-scale proteomics applications.

PMID- 15744834
TI  - Phosphoproteomic analysis using immobilized metal ion affinity chromatography on
      the basis of cellulose powder.
AB  - Detailed characterization of phosphoproteins as well as other post
      translationally modified proteins such as glycoproteins, is required to fully
      understand protein function and regulatory events in cells and organisms.
      Therefore, an experimental strategy for the isolation of phosphoproteins using a
      new immobilized metal ion affinity chromatograph (IMAC) material on the basis of
      cellulose has been developed and characterized. Different approaches have been
      used to test the material. Recovery rates were determined by 32P labelling of a
      myelin basic protein fragment and by reversed-phase high-performance liquid
      chromatography-electrospray ionization mass spectrometry using a tryptic digest
      of the model protein bovine beta-casein. Selectivity was demonstrated by
      enrichment and separation of phosphopeptides from different samples, such as from
      a digest of horse myoglobin as well as from a digest of in vitro phosphorylated
      extracellular signal regulates kinase 2 (ERK2) mixed with synthetic
      phosphopeptides, phosphorylated on different amino acid residues. Furthermore,
      simplification and optimization of sample pretreatment was achieved by combining
      the separating (IMAC) and desalting (C18) step during preparative high
      performance liquid chromatography. The comparison between our material and a
      commercially available IMAC system (POROS 20 MC; Perspective BioSystems)
      emphasizes the competitiveness of the cellulose. Confirmed by the obtained data,
      the cellulose material performed as well as the commercially available sorbent,
      however with the advantage, that it can be produced rather easily and at very low
      cost.

PMID- 15744835
TI  - PRIME: a graphical interface for integrating genomic/proteomic databases.
AB  - Data mining, finding and integration of information about proteins of interest,
      is an essential component in modern biological and biomedical research. Even when
      focusing on a single organism and only on a small number of proteins, there are
      often dozens fo data sources containing relevant information. We are developing
      PRIME, a protein information environment, to serve as a virtual central database
      which integrates distributed heterogeneous information about proteins (linked by
      common identifier). PRIME has powerful capabilities to visualize all kinds of
      protein annotation in specialized views. These views can be displayed side by
      side at the same time and can be synchronized in order to show simultaneously
      different aspects of identical proteins. These features allow a quick and
      comprehensive overview of properties of single proteins or protein sets.

PMID- 15744836
TI  - Application of partial least squares discriminant analysis to two-dimensional
      difference gel studies in expression proteomics.
AB  - Two-dimensional difference gel electrophoresis (DIGE) is a tool for measuring
      changes in protein expression between samples involving pre-electrophoretic
      labeling ith cyanine dyes. In multi-gel experiments, univariate statistical tests
      have been used to identify differential expression between sample types by
      looking for significant changes in spot volume. Multivariate statistical tests,
      which look for correlated changes between sample types, provide an alternate
      approach for identifying spots with differential expression. Partial least
      squares-discriminant analysis (PLS-DA), a multivariate statistical approach, was
      combined with an iterative threshold process to identify which protein spots had
      the greatest contribution to the model, and compared to univariate test for three
      datasets. This included one dataset where no biological difference was expected.
      The novel multivariate approach, detailed here, represents a method to complement
      the univariate approach in identification of differentially expressed protein
      spots. This new approach has the advantages of reduced risk of false-positives
      and the identification of spots that are significantly altered in terms of
      correlated expression rather than absolute expression values.

PMID- 15744837
TI  - Synthesis of Ag/BSA composite nanospheres from water-in-oil microemulsion using
      compressed CO2 as antisolvent.
AB  - In this work, a novel route to synthesize biomolecule/metal composite nanospheres
      is proposed. This method combines the advantages that the silver nanoparticles
      and bovine serum albumin (BSA) can be precipitated simultaneously from water-in
      oil microemulsion by the easy control of CO2 pressure, which was revealed by our
      high-pressure UV-VIS spectra. The Ag/BSA nanocomposites were successfully
      prepared using this method. The transmission electronic microscopy (TEM) if the
      obtained nanocomposites shows that the small-sized Ag nanaoparticles are
      immobilized by the BSA nanospheres, and the phase structure was characterized by
      X-ray diffraction (XRD). The Ag/BSA nanocomposites show absorption properties at
      a wavelength around 435 nm.

PMID- 15744838
TI  - Eye lens proteomics: from global approach to detailed information about phakinin
      and gamma E and F crystallin genes.
AB  - Exploration of the lenticular proteome poses a challenging and worthwhile
      undertaking as cataracts, the products of a disease phenotype elicited by this
      proteome, remains the leading cause of vision impairment worldwide. The complete
      ten day old lens proteome of Mus musculus C57BL/6J was resolved into 900 distinct
      spots by large gel carrier ampholyte based 2-DE. The predicted amino acid
      sequences of all 16 crystallins ubiquitous in mammals were corroborated by mass
      spectrometry (MS). In detailed individual spot analyses, the primary structure of
      the full murine C57BL/6J beaded filament component phakinin CP49 was sequenced by
      liquid chromatography/electrospray ionization-tandem MS and amended at two
      positions. This definitive polypeptide sequence was aligned to the mouse genome,
      thus identifying the entire C57BL/6J genomic coding region. Also, two murine
      C57/6J polypeptides, both previously classified as gamma F crystallin, were
      clearly distinguished by MS and electrophoretic mobility. Both were assigned to
      their respective genes, one of the polypeptides was reclassified as C57BL/6J
      gamma E crystallin. Building on these data and previous investigations an updated
      crystallin reference map was put forth and several non crystallin lenticular
      components were examined. These results represent the first part of a
      comprehensive investigation of the mouse lens proteome (http://www.mpiib
      berlin.mpg.de/2D-PAGE) with emphasis on understanding genetic effects on proteins
      and disease development.

PMID- 15744839
TI  - In situ extraction strategy affects benzophenanthridine alkaloid production
      fluxes in suspension cultures of Eschscholtzia californica.
AB  - The effect of contact between cells and extractive phase on secondary metabolite
      production was investigated in two-phase suspension cultures of Eschscholtzia
      californica. A system was designed to extract benzophenanthridine alkaloids from
      the cell culture, without contact between XAD-7 resins and the cells: only medium
      was recirculated through a column packed with the extractive phase. This strategy
      was compared to the classic method of addition of resins directly into the cell
      suspension. Removal of the product directly from the medium enabled important
      increases in production of alkaloids, namely a 20-fold increase in sanguinarine
      production and a 10-fold increase in chelerythrine, with high recovery in the
      resin. The recirculation strategy greatly simplified the production process since
      the resins are easily recovered from the cell culture and enable harvest of
      product without termination of culture. However, due to limited flow rate, the
      recirculation strategy was slightly less effective than direct addition of resins
      into the cell suspension. In addition to enabling increased production, removal
      of secondary metabolites from the medium changed metabolic flux distribution,
      testifying to a complex control mechanism of production.

PMID- 15744840
TI  - Engineering hepatocellular morphogenesis and function via ligand-presenting
      hydrogels with graded mechanical compliance.
AB  - In order to evaluate the sensitivity of hepatocellular cultures to variations in
      both substrate stiffness and bioactive ligand presentation, hepatocytes were
      cultured on differentially compliant polyacrylamide gel discs functionalized with
      varying amounts of the ECM ligand, fibronectin (FN). Subconfluent cell cultures
      were established in a multiwell plate format enabling the systematic evaluation
      of cellular response to both underlying substrate rigidity and substrate ligand
      concentration. Hepatocellular morphogenesis, regulated by a combination of both
      ligand density and substrate compliance, resulted in a broad spectrum of patterns
      of cellular reorganization and assembly ranging from highly two-dimensionally
      spread cells to highly compact, three-dimensional spheroids. Cell compaction was
      promoted by increasing levels of substrate mechanical compliance and generally
      inhibited by increasing concentrations of substrate-bound FN. We identified
      regimes of substrate compliance in which cells are highly responsive or
      relatively insensitive to the level of substrate-based ligands. For example,
      while FN presentation did not have a large impact on cell morphogenesis for
      cultures on highly compliant gels (G' = 1.9 kPa), hepatocytes on "firm"
      substrates of intermediate compliance (G' = 5.6 kPa) exhibited approximately a 2
      fold increase in cell area between the highest and lowest FN concentrations used
      in this study. Further, we show that increasing substrate compliance at constant
      ligand concentration results in increased levels of liver-specific albumin
      secretion while increasing levels of FN at constant substrate rigidity yield
      reduced liver-specific functional activity. These substrate-elicited differences
      in cell function also coincided with analogous changes in the transcript levels
      of metabolic, growth-related, and liver-specific gene markers. Notably, these
      results also demonstrated that "firm" gel substrates elicit the most hepatocyte
      functional sensitivity to substrate-based FN presentation. Overall, our findings
      indicate that hepatocellular responsiveness to ligand concentration can be
      acutely regulated by gradation of substrate compliance, suggesting that concerted
      biochemical and biophysical design strategies may be critical toward the
      fabrication of hepatospecific biomaterials that effectively support desired
      levels of liver-specific function.

PMID- 15744841
TI  - Quantification of oxygen release by bulrush (Scirpus validus) roots in a
      constructed treatment wetland.
AB  - Amount of oxygen released by bulrush (Scirpus validus) roots has been quantified
      based on the radial oxygen loss (ROL) exhibited by the roots, the number and the
      length of active lateral roots, and the field plant density. It was found that
      wetland bulrush contains two types of active lateral roots (showing ROL), viz.,
      laterals of brown and white main roots. The two laterals have distinct oxygen
      release characteristics. Based on the dissolved oxygen (DO) microprofiles of
      brown and white laterals, the ROLs were found to be approximately 61 ng O2 cm(-2)
      root surface min(-1) and approximately 68 ng O2 cm(-2) root surface min(-1),
      respectively, at bulk 5-day biochemical oxygen demand (BOD5) of 76 mg L(-1). The
      respective average active root lengths of the brown and the white laterals were
      approximately 40 and approximately 1676 microm. Based on field and laboratory
      measurements, the average amount of oxygen released by bulrush was found to be
      2.30 mg O2 m(-2) wetland surface d(-1); of this approximately 71% is from the
      white roots. The results of this study indicate that plants do not release enough
      oxygen to meet the total oxygen demand of bulk wastewater, and therefore,
      constructed wetlands should be designed as an anaerobic or an aerobic-anaerobic
      hybrid system rather than as an aerobic system. However, the results of this
      study should be viewed in the background of possible errors (including a reactor
      design flaw), which might have made the measured oxygen release significantly
      lower than what plant roots actually release. Further studies are needed to
      quantify wetland plant oxygen release based on micro-scale measurements.

PMID- 15744842
TI  - Effect of nitric oxide on catharanthine production and growth of Catharanthus
      roseus suspension cells.
AB  - Sodium nitroprusside (SNP) was used as the donor of nitric oxide (NO) to
      investigate its effect on catharanthine synthesis and the growth of Catharanthus
      roseus suspension cells. The results showed that SNP at high concentrations (10.0
      and 20.0 mmol/L) stimulated catharanthine formation of C. roseus cells, but
      inhibited growth of the cells. Low concentrations of SNP (0.1 and 0.5 mmol/L)
      enhanced the growth of C. roseus cells, but had no effect on catharanthine
      synthesis. The maximum total catharanthine production was achieved by the
      addition of 0.5 and 10.0 mmol/L SNP to the cultures at day 0 and day 10,
      respectively, being about threefold of the control. NO-induced catharanthine
      production of C. roseus cells was strongly suppressed by jasmonic acid (JA)
      biosynthesis inhibitor ibuprofen (IBU) and nordihydroguaiaretic (NDGA). The
      result suggests that the stimulatory role of NO on catharanthine production is
      partially JA-dependent.

PMID- 15744843
TI  - Central nervous system AIDS--related diseases.
AB  - The neurological complications of HIV contribute importantly to patient morbidity
      and mortality. Major common AIDS-related CNS diseases are ADC, metabolic
      encephalopaties, CMV encephalitis, TE, PCNSL, PML, criptococcal meningitis, and
      aseptic meningitis. After HAART, declines in incidence and improved outcome of
      several HIV-1 related opportunistic infections, including CNS-ADIs have been
      reported. The differential diagnosis of CNS complications of AIDS is routinely
      established according to temporal evolution, clinical data, and neuroradiological
      imaging. Combining neuroradiological imaging with the new CSF PCR tests may
      improve the diagnostic accuracy of some CNS-ADIs without the need of stereotactic
      brain biopsy, that may become limited to the situations where data remain
      conflicting.

PMID- 15744844
TI  - Mild head injury: revisited.
AB  - OBJECTIVE: 1. To define the incidence of positive CT scans in patients with
      different grades of mild head injury (MHI), 2. To identify clinical predictors of
      positive CT scans, 3. To evaluate the usefulness of plain radiographs in the
      triage of patients with MHI, 4. To evaluate frequency and nature of surgical
      intervention in MHI, 5. To evaluate the risk of deterioration in MHI, and 6. To
      find out whether patients with normal neurological examination and normal CT can
      be safely discharged. METHODS: In a prospective study conducted over a period of
      four months in our center, all patients with mild head injury (defined as Glasgow
      Coma Scores (GCS) 13-15) were admitted to the head injury unit. Patients
      underwent standard clinical examination, skull radiography and cranial CT. No
      clinical criteria were used to select patients for CT scanning and all the
      patients were subjected to CT. Patients with negative findings on CT and a normal
      neurological examination were discharged after 24 hours of observation. Patients
      with positive findings on cranial CT were treated either medically or surgically
      as deemed necessary. Outcome measures included safe discharge, clinical
      deterioration, need for surgical intervention or death. The following factors
      were analyzed statistically to find out whether they can be used as predictive
      factors for positive cranial CT. They were: age, sex, mode of injury, loss of
      consciousness, post-traumatic seizures, ear/ nose/throat bleeding, vomiting,
      admission GCS score, scalp injury, polytrauma, focal neurological deficit,
      fractures visualized on skull radiography. RESULTS: Three hundred and eighty one
      patients were included in the study. Of these males constituted 63%, females 17%
      and children 20%. RTA was the most common mode of injury. Seventy five percent of
      the patients had GCS of 15, 15% had GCS of 14 and 10% had GCS of 13. Thirty eight
      percent of the patients had positive findings on the CT. Age, mode of injury,
      loss of consciousness, post-traumatic seizures, ENT bleeding, vomiting, scalp
      injury and polytrauma were not found to be predictors of positive CT. Admission
      GCS score, focal neurological deficits, and fractures detected by skull
      radiography were found to be statistically significant predictors of positive
      findings on CT. Seven percent of patients required surgical intervention. Six
      percent of patients showed neurological deterioration and there was one death in
      this series of MHI patients. Patients with multiple lesions on CT had a higher
      chance of deterioration than those with a single lesion. No patient who had a GCS
      of 15 and normal CT developed any complication during the hospital stay or after
      discharge. CONCLUSIONS: The incidence of positive CT scans in this prospective,
      consecutive, unselected cohort of MHI patients was 38%. Lower admission GCS
      scores, focal neurological deficits, and fractures detected by skull x-rays were
      found to be significant predictors of positive CT. Other clinical parameters were
      not found to be predictors of positive CT. CT was found to be superior to plain x
      rays in detecting skull fractures. Seven percent of this cohort required
      neurosurgical intervention. Six percent showed neurological deterioration and
      there was one death in this series. Patients with multiple lesions on CT had a
      higher chance of deterioration than those with single lesions. The duration of
      hospital stay was prolonged in patients with positive CT. As no patient with a
      normal neurological examination and a normal CT deteriorated, we believe these
      patients can be safely discharged without need for admission and observation.

PMID- 15744845
TI  - Co-existence of unruptured cerebral aneurysms in patients with hypertensive
      intracerebral hemorrhage.
AB  - OBJECTIVE: Primary hypertensive intracerebral hemorrhage (PICH) is caused by a
      rupture of a small endartery, and diagnosis is made either by computed tomography
      (CT) or magnetic resonance imaging (MRI). Vascular abnormalities are not always
      evaluated in detail. In this study, we aimed to clarify the incidence of co
      existing vascular abnormalities, especially unruptured cerebral aneurysms by
      reviewing selective intraarterial digital subtraction angiography (DSA) images in
      PICH patients. METHODS: The cases of 169 hypertensive PICH patients who underwent
      selective intra-arterial DSA were reviewed. In all cases, CT or MRI showed no
      abnormality other than PICH, such as subarachnoid hemorrhage, component of
      arterio-venous malformation or cerebral tumor. The main reason for performing DSA
      was to exclude other causes of intracerebral hemorrhage such as ruptured cerebral
      aneurysm or small arterio-venous malformation prior to surgical removal of the
      hematoma. RESULTS: There were 33 patients with vascular abnormalities: unruptured
      cerebral aneurysm (n = 24, 14.2%), major vessels occlusion or stenosis (n= 8,
      4.7%), and dural arterio-venous fistula (n = 1). Unruptured cerebral aneurysms
      were found in 9.4% of men and 20.5% of women. CONCLUSION: Vascular abnormalities
      co-existing with PICH are not rare, suggesting the necessity for angiographic
      evaluation. Special attention should be given to female PICH patients who have a
      high incidence of having an unruptured cerebral aneurysm.

PMID- 15744846
TI  - Brain stem venous congestion due to dural arteriovenous fistulas of the cavernous
      sinus.
AB  - BACKGROUND: Venous congestion of the brain stem due to dural arteriovenous
      fistulas (DAVFs) in the cavernous sinus is rare and presents therapeutic
      challenges. To assess the prognosis of patients with symptomatic DAVFs and brain
      stem dysfunction, we evaluated the degree of venous ischemia by examining pre-
      and post-treatment magnetic resonance images (MRI) in 2 patients presenting with
      venous congestion of the brain stem. METHODS: A 56-year-old woman with left
      hemiparesis and a 70-year-old woman with gait disturbance attributable to right
      cavernous sinus DAVFs were referred to our hospital. In both cases, T2-weighted
      magnetic resonance imaging (MRI) disclosed a hyperintensity lesion in the
      brainstem due to venous congestion. FINDINGS: Both patients underwent open
      surgery for direct embolization of the cavernous sinus because there were no
      approach routes for transvenous embolization. The patient whose pretreatment MRI
      demonstrated Gd enhancement continued to manifest neurological deficits and
      persistence of the abnormal hyperintensity on post-treatment T2-weighted MRI. In
      the other patient whose pretreatment MRI showed no Gd enhancement, treatment
      produced a complete response of her neurological deficit and disappearance of the
      abnormal hyperintensity area. CONCLUSIONS: We tentatively conclude that lesions
      corresponding to hyperintensity areas on non-Gd-enhanced, T2-weighted MRI may
      reflect a reversible condition whereas lesions identified as hyperintense areas
      on GD-enhanced T2-weighted MRI may be indicative of irreversibility.

PMID- 15744847
TI  - Use of the prone oblique position in surgery for posterior fossa lesions.
AB  - BACKGROUND: The lateral suboccipital approach has been conventionally performed
      with the lateral, park-bench, or sitting position and the midline suboccipital
      approach has been performed in the prone position. We attempt to show the
      advantages of the prone oblique position in the surgery for posterior fossa
      lesions. METHODS: Twenty-two patients with posterior fossa lesions underwent
      surgery in the prone oblique position. The patients were fixed in the prone
      position while the operating table was rotated to raise the patient's shoulder.
      The surgeon sat beside the downward-shifted contralateral shoulder of the
      patient. With the lateral suboccipital approach, the neck of the patient was
      rotated to the side of the lesion. With the midline suboccipital approach, the
      neck was not rotated. FINDINGS: With the lateral suboccipital approach, this
      position spread the transverse axis of the suboccipital triangle and eliminated
      the interference of the patient's shoulder, providing an operative field that is
      wider than the lateral position or park bench position in all cases. With the
      midline suboccipital approach, this position enabled the surgeon to operate on
      lesions located in the upper half of the posterior fossa, such as fourth
      ventricular lesions or infratentorial lesions, without the need for a looking up
      posture with overhanging of the operative microscope. CONCLUSION: The prone
      oblique position offers the operator a panoramic view of the posterior fossa.

PMID- 15744848
TI  - Neurodegenerative effects of monopolar electrocauterization on spinal ganglia in
      lumbar disc surgery.
AB  - BACKGROUND: Monopolar electrocauterization (MEC) is widely used in spine surgery
      however electrical currents are hazardous for neural tissues, such as the spinal
      ganglia sited in the intervertebral foramina. We aimed to investigate the effects
      of MEC on spinal ganglia. METHOD: Fifteen male hybrid rabbits were included in
      the study. Three of the animals were used to analyze the findings regarding
      spinal ganglia without operation. The remaining animals underwent L4-5 disc
      surgery. For intra-operative facet denervation MEC was used for half of the
      animals. After one month, all animals were sacrificed and L5 spinal ganglia were
      removed for histopathological examination. The number and morphological changes
      of neurons in spinal ganglia were examined. FINDINGS: The mean number of live
      neurons was 22610 in non-operated rabbits; 21617 in the non-MEC group and 16692
      in the MEC group. Neuronal degeneration was more prominent in the MEC group than
      in the non-MEC group. CONCLUSIONS: MEC used during spine surgery may be injurious
      to spinal ganglia and should be used with caution.

PMID- 15744849
TI  - Delayed visual deterioration after pituitary surgery--a review introducing the
      concept of vascular compression of the optic pathways.
AB  - BACKGROUND: Delayed visual deterioration after pituitary surgery has been
      attributed to secondary empty sella syndrome and downward herniation of the optic
      nerves and chiasm, but the pathophysiological basis of this condition is still a
      matter of debate. REVIEW: According to the literature, prior radiation therapy,
      previous visual impairment and transcranial surgery constitute risk factors for
      delayed visual deterioration. Radiation-induced vascular changes and/or
      strangulation of the optic nerves or chiasm are thought to compromise local blood
      flow. Downward herniation of the optic pathways was present in the majority of
      cases, but did not correlate with visual symptoms and signs, while dense scarring
      of the chiasm was a reproducable finding in all surgically explored cases.
      Indentations in the upper margin of the optic nerves or chiasm caused by the A1
      segments of the anterior cerebral arteries have been reported repeatedly. As
      perichiasmal scarring constitutes the most consistent finding, the intimate
      relationship between artery and nerve with consecutive pulsatile pressure may
      constitute a causative factor in delayed visual dysfunction after pituitary
      surgery. The authors therefore introduce the concept of vascular compression,
      which is illustrated with a personal case of a successful decompression procedure
      with teflon interposition between the A1 segment and the non-herniated optic
      nerve to treat visual loss eight months following removal of a hemorrhagic
      pituitary adenoma. CONCLUSIONS: Clinicians should be aware that surgical
      exploration via a transcranial approach is indicated in cases of progressive
      visual loss late after pituitary surgery, no matter whether downward displacement
      of the optic pathways is present on imaging studies or not. Special attention
      should be paid intra-operatively to the dissection of the intimate relationship
      between the anterior cerebral arteries and the optic nerves and chiasm.

PMID- 15744850
TI  - Syringomyelia with Chiari malformation; 3 unusual cases with implications for
      pathogenesis.
AB  - Syringomyelia is an important cause of neurological deficit. Most cases of non
      traumatic syringomyelia occur in association with a Chiari malformation. We
      present three unusual examples of syringomyelia with such an association. The
      first case is that of syringomyelia in a young woman with Marfan's syndrome, a
      spontaneous CSF leak and intractable intracranial hypotension. The second is a
      woman with long-standing lumbo-peritoneal shunt for pseudotumour cerebri who
      developed an acquired Chiari malformation. A young woman with a Dandy-Walker cyst
      that herniated into the upper cervical canal is the third case. These cases
      provide a basis for discussion of the pathogenesis and management of
      syringomyelia and the Chiari malformation in such cases.

PMID- 15744851
TI  - Multilocated mature teratoma: a case report and review of the literature.
AB  - Mature teratomas are rare inclusion tumors, which have benign behaviors.
      Different locations of the tumor were reported in the literature. However,
      multiple tumor locations are extremely rare. An eight year old patient presented
      with an intraventricularly mature teratoma. During the six year follow up-period,
      two separately located masses were observed in the chest area and in the right
      iliac region, and both tumors were histologically diagnosed as mature teratomas.
      In this study, this unique case of mature teratoma presented with multiple
      locations in three separate body compartments. Furthermore, intraventricular
      dissemination with sellar and parasellar extension was observed in the third
      ventricle.

PMID- 15744852
TI  - Solitary intraventricular tuberculoma in adults.
AB  - Intracranial tuberculoma is typically located in the parenchyma. Lesions limited
      to the ventricular system are uncommon. It is difficult to make a differential
      diagnosis from other lesions if no systemic tuberculosis is present. This study
      investigates a case of solitary intraventricular tuberculoma in a 19-year-old
      female patient with an initial clinical symptom of progressive headache. Cranial
      computed tomography revealed a strongly enhanced lesion in the lateral ventricle.
      Histopathology of the tumor demonstrated chronic inflammation, caseous necrosis,
      epithelioid cells and Langhans' giant cell. The culture study grew M.
      Tuberculosis. Solitary intraventricular tuberculoma in adults is extremely rare.
      Medical treatment is the preferred management method of this disease, and
      surgical intervention should be considered in certain situations.

PMID- 15744853
TI  - Skull metastasis of follicular thyroid carcinoma.
AB  - Metastasis of a follicular thyroid carcinoma (FTC) to the skull is very rare. We
      present a case of solitary lytic skull metastasis of a FTC in a 30-year-old
      woman. The patient presented with bulging on the left side of the head. Neuro
      imaging techniques showed a lesion with an osteolytic component in the left
      frontal region. After a left frontal craniectomy the tumour was removed totally.
      The histopathological examination revealed a well-differentiated FTC metastasis
      and a complete total thyroidectomy was subsequently performed. The patient was
      given thyroid-stimulating hormone (TSH) suppression therapy followed by whole
      body iodine-131 (I131) internal radiation.

PMID- 15744854
TI  - 11 unanswered questions point to the future. In the year ahead, solving even one
      of the top unanswered questions in cardiology would be a boon to many.

PMID- 15744855
TI  - Chest pain centers getting stamp of approval. A new accreditation process could
      mean better care and fewer misdiagnosed heart attacks.

PMID- 15744856
TI  - Damaged heart? Grow around it! Researchers are racing to heal injured hearts by
      using stem cells from outside the heart, and maybe even ones inside it.

PMID- 15744857
TI  - Watching heart disease from a distance. New technology makes it easier to keep
      tabs on your heart, and heart disease.

PMID- 15744858
TI  - Wider coverage for home blood thinner checks.

PMID- 15744859
TI  - Ask the doctor. Almost 10 years ago, I had a stent implanted to prop open my
      blocked left anterior descending artery. At the time, my doctor told me, "This
      should hold you for five years or so." Are stents like cars, requiring periodic
      trade-ins? I haven't had any problems so far.

PMID- 15744860
TI  - Ask the doctor. Like President Clinton, I have four very clogged coronary
      arteries (70% to 90% closed). My cardiologist pushed for bypass surgery but I
      resisted. A year later, the blockages have decreased somewhat. I haven't had much
      luck finding out about complications from and survival after bypass surgery. Can
      you help?

PMID- 15744861
TI  - Boycott. Activists' campaign includes ATM draws.

PMID- 15744862
TI  - Pandemic. G7 finance ministers encouraged to drop debt in poor countries.

PMID- 15744863
TI  - Charity. Celebrities join AIDS Project Los Angeles to benefit AIDS.

PMID- 15744864
TI  - New world royalty serve as AIDS ambassadors.

PMID- 15744865
TI  - Employment. New York not liable for sickness that attacks HIV, diabetes.

PMID- 15744866
TI  - Prisons. Life sentence affirmed for HIV-positive inmate who spit on CO.

PMID- 15744867
TI  - African patients with HIV seek out herbal remedies.

PMID- 15744868
TI  - Buddy system gives hope in HIV/AIDS fight.

PMID- 15744869
TI  - State roundup. States take drastic measures to help those living with HIV.

PMID- 15744870
TI  - Bias. Court denies reconsideration on HIV-discrimination claim.

PMID- 15744871
TI  - 30-year sentence upheld for HIV-positive offender.

PMID- 15744873
TI  - Wrongful adoption. Parents' claims against adoption agency are time-barred.

PMID- 15744872
TI  - Threat of exposure. Menacing conviction of HIV-positive offender affirmed.

PMID- 15744874
TI  - Court-ordered HIV testing upheld for juvenile sex offender.

PMID- 15744875
TI  - Prison dentist not indifferent to HIV-positive inmates' needs.

PMID- 15744876
TI  - Ideology. amFAR reaffirms statement opposing research interference.

PMID- 15744877
TI  - HIV/AIDS vaccine group outlines strategic plan.

PMID- 15744878
TI  - Treatment. CDC urges wide use of AIDS drugs.

PMID- 15744879
TI  - Bush to boost PEPFAR funding; critics say more is needed.

PMID- 15744880
TI  - Court: bus driver must disclose HIV test results.

PMID- 15744881
TI  - Reduced sentence denied for inmate with AIDS.

PMID- 15744883
TI  - RAND study finds conspiracy beliefs deter condom use.

PMID- 15744882
TI  - Prevention. Report: HIV transmission to U.S. newborns nears extinction.

PMID- 15744884
TI  - HIV drugs. Court: influence of AIDS drugs no defense for murder.

PMID- 15744885
TI  - Fear of exposure. Petition for damages due to HIV fear fails on appeal.

PMID- 15744886
TI  - Criminal exposure. Mouth of HIV-positive inmate deemed a deadly weapon.

PMID- 15744887
TI  - Negligent transmission. HIV transmission lawsuit names restaurant and owner.

PMID- 15744889
TI  - Exposure. Charges reduced for HIV-positive man who bit guard.

PMID- 15744888
TI  - Criminal exposure. Man with HIV gets prison for having unprotected sex.

PMID- 15744890
TI  - Massive HIV/AIDS media campaign debuts third season.

PMID- 15744891
TI  - New fixed dose once-a-day combinations. Interview by John S. James.

PMID- 15744892
TI  - Taking the pulse of HIV medicine in Europe. IAPAC sessions 2004--Europe.
      September 23-24, 2004, London.

PMID- 15744893
TI  - HCV coinfection hastens HIV disease progression.

PMID- 15744894
TI  - Private practice physicians find dual role challenging.

PMID- 15744895
TI  - Safeguarding human genetic privacy.

PMID- 15744896
TI  - Understanding prohibitions against genetic discrimination in insurance.
AB  - The justification for laws prohibiting genetic discrimination in health insurance
      is not at all clear. Neither privacy protection, the distinctive features of
      health insurance, nor the distinction between presymptomatic genetic tendencies
      and actually manifested disease provide a justification, although certain
      practical considerations may justify these laws.

PMID- 15744897
TI  - Separating predictive genetic testing from snake oil: regulation, liabilities,
      and lost opportunities.
AB  - This article explores the extent to which completion of maps of the human genome,
      coupled with the introduction of technology that will accelerate the
      identification of gene and protein function, have introduced immeasurable
      potential to advance life science and health care through genetic profiling. In
      light of definitional uncertainty, the regulatory and legal environment
      surrounding predictive genetic testing threatens to impede clinical utilization
      of genetic profiling technologies that could significantly improve human health.
      Especially given that genetic testing technologies have been stigmatized in the
      public and medical community, they must enter the marketplace with a regulatory
      framework that assures safety, efficacy, and market responsibility.

PMID- 15744899
TI  - Who owns my body.

PMID- 15744898
TI  - Patients' bill of rights: legislative cure-all or prescription for disaster?

PMID- 15744900
TI  - Cloning consensus: creating a convention to ban human reproductive cloning.

PMID- 15744901
TI  - Commercialization of genetic testing services: the FDA, market forces, and
      biological tarot cards.
AB  - Many women fear being diagnosed with breast cancer, and rightfully so. Despite
      the capabilities of modern medicine, the cumulative lifetime risk of getting the
      disease has risen to one in eight and, despite decades of research, no cures
      exist. In this Article, the authors explore the commercialization of so-called
      breast cancer gene tests, based upon genetic alterations linked to the disease.
      Although the authors fully address this specific technology, they use what
      constitutes the seminal case of predictive genetic testing to analyze the
      adequacy of the existing regulatory framework. The authors conclude that the
      present regulatory system is inadequate and places a dangerous amount of reliance
      on primary care physicians. Their conclusion is grounded in the observation that
      most primary care physicians lack sufficient knowledge about this evolving
      investigative technology--which is highly subject to misinterpretation, and,
      though potentially helpful to some "high risk" patients, offers questionable
      clinical value for the general public. The authors set forth numerous proposals
      to promote both the quality and clinical value of predictive genetic testing so
      that it conforms to public health standards and can be properly integrated as a
      reliable component of medical care in specific situations.

PMID- 15744902
TI  - Panax notoginseng supplementation enhances physical performance during endurance
      exercise.
AB  - The purpose of this study was to investigate whether a single 1,350-mg dose of
      Panax notoginseng (PNG) could enhance aerobic capacity, endurance, and mean blood
      pressure (MAP) in young adults. We randomly assigned 29 untrained adults, aged 20
      35 years, to an experimental (EXP, n = 13) or a control (CON, n = 16) group. For
      30 days, the EXP took 1,350 mg per day of PNG capsule and the CON consumed 1,350
      mg per day of starch capsule. Measurement variables were taken before and after
      30 days of either PNG supplement or placebo. Results show that the EXP improved
      (p < 0.05) their endurance time by >7 minutes, and lowered (p < 0.05) maximal MAP
      (from 113 +/- 12 to 109 +/- 14 mm Hg) and Vo2 at the 24th minute (from 32.5 +/- 8
      to 27.6 +/- 8 ml.kg-1.min-1) during endurance cycle exercise. Based on this
      study, we conclude that 1,350 mg per day PNG supplement for 30 days improved
      endurance time to exhaustion, and lowered MAP and Vo2 during endurance exercise.

PMID- 15744903
TI  - How earnings and financial risk affect private accounts in Social Security reform
      proposals.

PMID- 15744904
TI  - Medical surrogacy mediation: expanding patient, family, and physician rights and
      reformulating the Virginia Health Care Decisions Act.

PMID- 15744905
TI  - Abstracts from the Society for Cardiovascular Magnetic Resonance 8th Annual
      Meeting. San Francisco, California, USA, January 21-23, 2005.

PMID- 15744906
TI  - Carnitine. The science behind a conditionally essential nutrient. Proceedings of
      a conference. March 25-26, 2004. Bethesda, Maryland, USA.

PMID- 15744907
TI  - Spate of suspensions of academic research spurs questions about federal strategy:
      a U.S. agency, its own future uncertain, unsettles college officials with its
      crackdown.

PMID- 15744908
TI  - U.S. regulators suspend medical studies at 2 universities.

PMID- 15744910
TI  - [Abstracts of the 98th French Congress of Urology. Paris, France, 17-20 November
      2004].

PMID- 15744909
TI  - Bioethics from the margins: Haitian immigrants and American health care.

PMID- 15744911
TI  - Conspiracy of silence: medical research and moral obligation.

PMID- 15744912
TI  - Clinical trials for children: in whose best interest?

PMID- 15744913
TI  - Where the innocent bear the consequences: lessons from an institution's IRB
      crisis.

PMID- 15744914
TI  - Abstracts of the 34th Annual Meeting of the German Society for Thoracic and
      Cardiovascular Surgery. February 13-16, 2005, Hamburg, Germany.

PMID- 15744915
TI  - In defense of dignity: the religious implications of human experimentation.

PMID- 15744916
TI  - Abstracts of the 54th Annual Scientific Session of the American College of
      Cardiology. March 6-9, 2005, Orlando, Florida, USA.

PMID- 15744917
TI  - Abstracts of the International Society for Heart and Lung Transplantation 25th
      Anniversary Meeting and Scientific Sessions. April 6-9, 2005, Philadelphia,
      Pennsylvania, USA.

PMID- 15744919
TI  - Recent advances in otitis media. Report of the Eighth Research Conference. June 3
      7, 2003. Fort Lauderdale, Florida, USA.

PMID- 15744918
TI  - Institutions, incentives and the future of fisheries.
AB  - Fisheries around the world are managed with a broad range of institutional
      structures. Some of these have been quite disastrous, whereas others have proven
      both biologically and economically successful. Unsuccessful systems have
      generally involved either open access, attempts at top-down control with poor
      ability to monitor and implement regulations, or reliance on consensus.
      Successful systems range from local cooperatives to strong governmental control,
      to various forms of property rights, but usually involve institutional systems
      that provide incentives to individual operators that lead to behaviour consistent
      with conservation.

PMID- 15744920
TI  - On payment by results and A&E.

PMID- 15744921
TI  - Finding doctors in Chicago: a project to improve online physician directories.
      Summary of findings and recommendations.
AB  - When consumers select new doctors, they often have limited information beyond
      their own prior experience and the recommendations of family and friends.
      Physicians, when making referrals to specialists, can also find themselves armed
      with inadequate data. With more people turning to the Internet as a source of
      health care information, online physician directories are becoming important
      resources. Unfortunately, these sites are frequently difficult to use, not
      objective, or contain information that is old, inaccurate, or incomplete. The
      Midwest Business Group on Health worked with stakeholders to find out what
      consumers and physicians like and dislike about online directories. According to
      the study's findings, online physician directories should maximize ease of use
      and navigation, for example, by incorporating sophisticated search functions and
      interactive features; provide a wide range of content, including information on
      physicians' practice style; and ensure the credibility of data by regularly
      updating and monitoring for accuracy.

PMID- 15744922
TI  - Antifibrinolytic agents in traumatic hemorrhage: a large scale randomized
      controlled trial is needed.

PMID- 15744923
TI  - Vaccination: fascination and poetry.

PMID- 15744925
TI  - Dietary management of chronic kidney disease patients: protein-restricted diets
      supplemented with keto/amino acids. Abstracts from the International Advisory
      Board Meetings 2003/2004.

PMID- 15744924
TI  - Triggering of sudden cardiac events by coffee and alcohol consumption: what do we
      know?

PMID- 15744926
TI  - Nurse managers. Moving with the times.

PMID- 15744927
TI  - Bloodborne infections in emergency medicine.

PMID- 15744928
TI  - Abstracts from TransplantAsia 2004. 1-4 December, Singapore.

PMID- 15744929
TI  - On battles for 2005.

PMID- 15744930
TI  - Mental illness and addiction issue brief: mental health courts: year end report
      2004.

PMID- 15744931
TI  - New health economies. Premium bond.

PMID- 15744932
TI  - Barometer. Acute trusts December 2004.

PMID- 15744933
TI  - Abstracts of the 24th Annual Convention of Indian Association for Cancer Research
      and International Symposium on Human Papillomavirus and Cervical Cancer. February
      9-12, 2005, Noida, India.

PMID- 15744934
TI  - On engaging communities.

PMID- 15744935
TI  - Regional focus: North East. Not so grim up north.

PMID- 15744936
TI  - Proceedings of the Seventh International Symposium on the Neurobiology and
      Neuroendocrinology of Aging. July 18023, 2004. Bregenz, Austria.

PMID- 15744937
TI  - A Festschrift in honor of the 60th birthday of Professor Fred Lewis.

PMID- 15744938
TI  - Antibiotics for neurological ailments?

PMID- 15744939
TI  - Gene mutation detected in Parkinson's disease.

PMID- 15744941
TI  - Canine epilepsy gene mutation identified.

PMID- 15744940
TI  - Christian Andreas Doppler--the man and his legacy.
AB  - AIMS: Reminding the life and legacy of the Austrian Scientist who discovered the
      famous 'Doppler Effect'. METHODS AND RESULTS: C.A. Doppler was born the 29th of
      November 1803 in Salzburg. After studies in Linz and Vienna, he graduated in
      mathematics, became assistant at the University and later worked as a professor
      in Prague. Back to Vienna, he was appointed as professor at the Polytechnic
      School and --in 1850--as first director of the new Institute of Physics. C.A.
      Doppler did publish on magnetism, electricity, optics, and astronomy. He remains
      in the history of science due to the discovery presented (May 25, 1842) at the
      Royal Bohemian Society of Science entitled "On the colored light of the double
      stars and certain other stars of the heavens"; the paper described (applied to
      light) the shift of frequency which bears nowadays his name. The theory was later
      experimentally proven and--extended for any electromagnetic and acoustic waves-
      got myriads if applications in astronomy, physics, aviation, meteorology, and
      health science. Satomura in Japan (1955) published it's first ultrasound vascular
      application--with successive achievements in the next decades. CONCLUSION:
      Doppler ultrasonagraphy became the main noninvasive instrument for functional
      assesment of heart and vessels.

PMID- 15744942
TI  - Iconic memory loss linked to onset of Alzheimer's disease.

PMID- 15744943
TI  - New era of transcranial magnetic stimulation.

PMID- 15744944
TI  - Uncovering the molecular side of alcohol addiction.

PMID- 15744945
TI  - A Festschrift in honour of Professor Rudy Juliano, winner of the 2004 Life-time
      Achievement Award from the Journal of Drug Targeting.

PMID- 15744946
TI  - A Festschrift in Honor of Warren A. Weinberg.

PMID- 15744947
TI  - Historical note. Neuralgic amyotrophy.

PMID- 15744948
TI  - How secure is the safety net? The future of the nation's community health care
      centers and public hospitals is grave.

PMID- 15744949
TI  - The Medicaid spending morass: Medicaid continues to grow at alarming rates
      causing states to seek solutions.

PMID- 15744950
TI  - Mental illness and addiction issue brief: psychotropic medication and children:
      year end report-2004.

PMID- 15744951
TI  - Mental illness and addiction issue brief: state suicide prevention efforts for
      children and adolescents: year end report-2004.

PMID- 15744953
TI  - Long-term care issue brief: assisted living: year end report-2004.

PMID- 15744952
TI  - An amperometric urea biosensor based on covalent immobilization of urease onto an
      electrochemically prepared copolymer poly (N-3-aminopropyl pyrrole-co-pyrrole)
      film.
AB  - An amperometric biosensor has been developed for the quantitative determination
      of urea in aqueous solution. The principle is based on the use of pH-sensitive
      redox active dissolved hematein molecule. The enzyme, urease (Urs), was
      covalently immobilized on a conducting copolymer poly (N-3-aminopropyl pyrrole-co
      pyrrole) film, electrochemically prepared onto an indium-tin-oxide (ITO)-coated
      glass plate. The covalent linkage of enzyme and porous morphology of the polymer
      film lead to high enzyme loading and an increased lifetime stability of the
      enzyme electrode. Amperometric response was measured as a function of
      concentration of urea, at fixed bias voltage of 0.0 V vs. Ag/AgCl in a phosphate
      buffer (pH 7.0). The electrode gives a linear response range of 0.16-5.02 mM for
      urea in aqueous medium. The response time is 40 s reaching to a 95% steady-state
      current value, and 80% of the enzyme activity is retained for about 2 months.

PMID- 15744954
TI  - Abstracts of the 6th International Congress of Pediatric Otorhinolaryngology.
      Athens, Greece, 16-19 May 2004.

PMID- 15744956
TI  - Intrascleral nerve loops.

PMID- 15744957
TI  - Changes of refraction after cataract surgery.

PMID- 15744958
TI  - Some observation on visual function in 204 sellar lesions.

PMID- 15744959
TI  - Uncommon sinus lesions as a cause of proptosis (a clinical study).

PMID- 15744960
TI  - Local anesthesia in cataract surgery.

PMID- 15744961
TI  - Myxosarcoma of the orbit (a case report).

PMID- 15744962
TI  - Orbital rhabdomyosarcoma.

PMID- 15744963
TI  - Malignant melanoma of conjunctiva.

PMID- 15744965
TI  - Abnormal regeneration of oculomotor nerve (case report).

PMID- 15744966
TI  - Congenital iridodialysis.

PMID- 15744964
TI  - Oculomotor nerve paralysis of unknown aetiology (a clinical study).

PMID- 15744967
TI  - Amblyopia development due to lack of functional, stimulation of visual pathways.

PMID- 15744968
TI  - Acquired cataract in homocystinuria.

PMID- 15744969
TI  - Failure of filtering bleb after threphination and its management.

PMID- 15744970
TI  - Lack of retinal correspondence.

PMID- 15744971
TI  - Primary reticulo-endothelial tumours of orbit.

PMID- 15744972
TI  - Ocular injuries in childhood.

PMID- 15744973
TI  - Congenital Fuchs dystrophy.

PMID- 15744974
TI  - Xanthomatosis as a cause of unilateral proptosis.

PMID- 15744975
TI  - 'neonatal uvieitis'.

PMID- 15744976
TI  - Role of Hyaluronidase (Hyalase) in management of pterygium.

PMID- 15744977
TI  - Average distribution of intraocular pressure in Indians by applanation tonometer.

PMID- 15744978
TI  - Macular function tests with special reference to photostress test.

PMID- 15744979
TI  - Macular illumination tests in various refractive states of the eye.

PMID- 15744980
TI  - Macular illumination tests in macular solar burns.

PMID- 15744981
TI  - Macular illumination tests in amblyopia.

PMID- 15744982
TI  - A study of effects of premedication with Pethidine, Largactil and Siquil used
      individually and in different combinations in cataract surgery.

PMID- 15744983
TI  - Bacterial and fungal flora of the normal eye.

PMID- 15744984
TI  - Methandienone (Dianabol) in corneal ulcers.

PMID- 15744985
TI  - Juvenile amaurotic family idiocy with cherry-red spot and cataract.

PMID- 15744986
TI  - Bilateral proptosis with acute myeloid leukaemia.

PMID- 15744987
TI  - Synthesis of highly luminescent glasses incorporating cdte nanocrystals through
      sol-gel processing.
AB  - Highly photoluminescent glass was prepared by embedding water-soluble
      nanocrystals in a glass matrix using a novel sol-gel process. Thiol-stabilized
      CdTe nanocrystals and aminopropyltrimethoxysilane were found to be the best
      combination in the preparation. The synthesis process had to be optimized to
      avoid nanocrystal agglomeration. The nanocrystals thus embedded in the glass
      matrix did not show any deterioration of the surface condition. The obtained
      glass combines excellent optical properties of nanocrystals with the high
      stability of glass; it emits light of various colors with narrow emission spectra
      and high photoluminescent efficiency (41%).

PMID- 15744988
TI  - Immobilization of the nanoparticle monolayer onto self-assembled monolayers by
      combined sterically enhanced hydrophobic and electrophoretic forces.
AB  - The immobilization of surface-derivatized gold nanoparticles onto methyl
      terminated self-assembled monolayers (SAMs) on gold surface was achieved by the
      cooperation of hydrophobic and electrophoretic forces. Electrochemical and
      scanning probe microscopy techniques were utilized to explore the influence of
      the SAM's structure and properties of the nanoparticle/SAM/gold system. SAMs
      prepared from 1-decanethiol (DT) and 2-mercapto-3-n-octylthiophene (MOT) were
      used as hydrophobic substrates. The DT SAM is a closely packed and organized
      monolayer, which can effectively block the underlying gold and inhibit a variety
      of solution species including organic and inorganic molecules from penetrating,
      whereas the MOT monolayer is poorly packed or disorganized (because of a large
      difference in dimension between the thiophene head and the alkylchain tail) and
      permeable to many organic probes in aqueous solution but not to inorganic probes.
      Thus, the MOT monolayer provides a more energetically favorable hydrophobic
      surface for the penetration and adsorption of organic species than the DT
      monolayer. This hypothesis is supported by experiments in which the density of
      hydrophobically immobilized nanoparticles on the MOT SAM is much larger than that
      on the DT SAM. The results also suggest new approaches for modification of
      macroscopic surfaces with nanoscopic particles.

PMID- 15744989
TI  - Freeze fracture direct imaging of a viscous surfactant mesophase.
AB  - Freeze fracture direct imaging (FFDI) has been used to image microstructures
      present in a highly viscous four-component mesophase containing water, isooctane,
      AOT [bis(2-ethylhexyl) sodium sulfosuccinate], and lecithin. As water is added to
      a fixed amount of a ternary solution of isooctane and the two surfactants, the
      microstructure evolves from a water-in-oil microemulsion, to a highly viscous
      columnar hexagonal, and then to multilamellar vesicles. Each of these
      microstructures is imaged directly. Previous small-angle neutron scattering
      measurements have identified the lamellar phase, but the FFDI technique
      demonstrates that these are onionlike curved multilamellar structures rather than
      planar bilayers. Freeze fracture direct imaging expands the range of cryo
      transmission microscopy to highly viscous, high-organic-content systems that
      typically have been difficult to visualize.

PMID- 15744990
TI  - Microelectrochemical approach to induce local cell adhesion and growth on
      substrates.
AB  - The nature of an albumin-coated substrate that blocks protein adsorption and cell
      adhesion was rapidly switched to cell-adhesive by exposure to an oxidizing agent
      such as HBrO. This finding has enabled cellular pattern drawing even on a single
      cell level by closely scanning a microelectrode above the substrate and
      electrochemically producing the agent at the tip of the electrode. The present
      microelectrochemical cell patterning is applicable even for a previously cell
      patterned substrate and for a grooved substrate. These unique technical features
      will have impacts on a variety of cell-based studies that require the analysis of
      heterotypic cell-cell interactions and cellular arrangement on an uneven surface
      such as semiconductor devices.

PMID- 15744991
TI  - Facile tailoring of film morphology and release properties using layer-by-layer
      assembly of thermoresponsive materials.
AB  - Layer-by-layer self-assembly was used to prepare thermoresponsive thin films of
      poly(N-isopropylacrylamide) (PNIPAAm) and poly(acrylic acid) (PAA) based on
      hydrogen bonding. The temperature of PNIPAAm adsorption was shown to
      significantly affect both the mass proportion of PNIPAAm in the film and the film
      surface morphology. When the adsorption was conducted at temperatures close to
      the lower critical solubility temperature of PNIPAAm, the amount of PNIPAAm in
      the film increased significantly (from 51 to 59%), and the total film mass
      increased by 30-40%. The films prepared at 30 degrees C also exhibited a lower
      surface roughness (1-2 nm) compared with 5-8 nm when prepared at 10 or 21 degrees
      C. The resulting multilayer films ([PAA/PNIPAAm]10) were capable of being
      reversibly loaded and unloaded with dye (Rhodamine B) by exposure to solutions at
      elevated temperatures. The rate of loading and release was shown to depend on
      both the solution temperature and film preparation temperature, leading to
      tunable loading/release properties.

PMID- 15744992
TI  - Photoluminescence resulting from semiconductor-metal solid solution observed in
      one-dimensional semiconductor nanostructures.
AB  - A narrow band photoluminescence (PL) emission peak resulting from CdS-Au solid
      solution was observed when growing one-dimensional nanostructures of CdS via the
      vapor-liquid-solid mechanism by using Au as the catalyst. This emission peak was
      located at 680 nm, a wavelength longer than the near band edge emission of CdS at
      520 nm, and was shown not to be caused by the usual trap states of CdS which lead
      to a broad band emission. Here, the one-dimensional nanostructures of CdS were
      grown in a simple, low-temperature (360 degrees C) metal-organic chemical vapor
      deposition process with a single source precursor of CdS. Straight nanowires of
      diameter 50-70 nm and wormlike nanorods of diameter 100-200 nm were obtained.
      Both the upper and lower portions of the nanorods/nanowires possessed single
      crystallinity as judged from the corresponding high-resolution transmission
      electron microscopy images and selected area electron diffraction data. This work
      demonstrates the feasibility of adjusting PL emission peaks of optoelectronic
      semiconductors through alloying with metals.

PMID- 15744993
TI  - Synthesis and characterization of single-crystalline In2O3 nanocrystals via
      solution dispersion.
AB  - In this paper, In2O3 nanocrystals were prepared by solution dispersion from bulk
      indium. In2O3 nanocrystals with an average diameter of 30 nm have a single
      crystalline phase and appear as a square or rhombohedral shape, and little
      spherical particles are also present. In addition, these nanocrystals show strong
      ultraviolet-blue emission.

PMID- 15744994
TI  - Ion exchange at a surface monolayer.
AB  - Total reflection total conversion electron yield X-ray absorption fine structure
      is applied to the evaluation of ion exchange occurring at the surface monolayer
      of two-tailed ammonium ions. X-ray absorption measurements at a Br K-edge allow
      us to detect ion-exchange equilibria between Br- and Cl- added in a subphase. The
      ion-exchange selectivity of Br- over Cl- basically increases as the monolayer is
      compressed, indicating that Cl- is selectively squeezed out by compression
      because of its larger hydrated ionic radius.

PMID- 15744995
TI  - Surfactant aggregation within room-temperature ionic liquid 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide.
AB  - On the basis of the response of solvatochromic probes [Reichardt's betaine dye,
      pyrene, and 1,3-bis(1-pyrenyl)propane], we have investigated the aggregation
      behavior of common anionic, cationic, and nonionic surfactants when solubilized
      within a low-viscosity room-temperature ionic liquid 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide (emimTf2N). We observed possible aggregate
      formation by all nonionic surfactants included in the study (Brij-35, Brij-700,
      Tween-20, and Triton X-100), while no aggregation was observed for the cationic
      surfactant cetyltrimethylammonium bromide. The anionic surfactant sodium dodecyl
      sulfate does not appear to solubilize within emimTf2N at ambient conditions.

PMID- 15744996
TI  - Determination of molecular ordering at a buried interface and the effect of
      interfacial ordering on thin film crystallization by second harmonic generation.
AB  - It is demonstrated that by using optical second harmonic generation the
      orientation and alignment of molecules in the interfacial layer between two
      solids, a thin solid molecular film and a metal substrate, can be determined. The
      pyridine molecules in the interfacial layer underneath the film are found to
      align along the [110] direction of the Ag(110) surface with a small tilt angle
      (approximately 11 degrees) from the surface normal. This interfacial ordering is
      found to have a notable effect in inducing crystallization at the heterogeneous
      boundary of the amorphous molecular film.

PMID- 15744997
TI  - Homogeneous nucleation of water in mesoporous zeolite cavities.
AB  - In this paper, we show that water inside mesoporous cavities in zeolites can be
      supercooled to ca. -40 degrees C at which point homogeneous nucleation of the
      water takes place. The fundamental phenomena observed here are similar to those
      reported earlier in for example emulsion droplets or droplets in the vapor phase.
      However, as these zeolite materials are widely available, they may provide an
      easily accessible source for studies of supercooled liquids in confinements. Next
      to this, it is now possible to discriminate with thermoporometry between
      mesoporous cavities inside the zeolite crystals, in which homogeneous nucleation
      takes place, and mesopores that are connected to the external surface in which
      heterogeneous nucleation takes place.

PMID- 15744999
TI  - Effect of the nature of the spacer on the aggregation properties of gemini
      surfactants in an aqueous solution.
AB  - The aggregation properties of three dicationic quaternary ammonium gemini
      surfactants with the same structure, except the spacer group, diethyl ether, six
      methylene, and p-xylyl, have been studied using electrical conductivity and
      fluorescence. The critical micelle concentration (cmc) and the micelle
      aggregation number (N) were determined, and the micropolarity and the
      microviscosity of the micelle were characterized. The micelle ionization degree
      (alpha) was obtained by a combination of the electrical conductivity data and the
      micelle aggregation number. Furthermore, the Gibbs free energy of micellization
      (deltaGmic) was studied. These results have shown that the nature of the spacer
      has an important effect on the aggregation properties of gemini surfactants in an
      aqueous solution. A hydrophilic, flexible spacer prompts micelle formation, which
      leads to a smaller cmc, smaller alpha, larger N, and more negative deltaGmic.
      Meanwhile, the microviscosity study indicates that the gemini surfactant with a
      hydrophilic, flexible spacer forms a more closely packed micelle structure than
      the one with a hydrophobic, rigid spacer.

PMID- 15744998
TI  - Coarsening of alkane-in-water emulsions stabilized by nonionic poly(oxyethylene)
      surfactants: the role of molecular permeation and coalescence.
AB  - We produce different alkane-in-water concentrated emulsions stabilized by the
      same nonionic surfactant, and we follow their kinetic evolution by granulometry.
      The size distribution becomes remarkably narrow during the first stages of
      coarsening and progressively turns to a wide function as time passes. We get
      evidence that the size evolution occurs under the effect of molecular permeation
      and coalescence. A second hydrophobic species of large molecular size is
      dissolved in the dispersed phase. This latter is expected to inhibit the
      permeation mechanism, and coalescence should act alone. Surprisingly, coalescence
      is also suppressed, even at a very low concentration of the second component
      (approximately 1% w/w). We vary the chemical nature and concentration of the
      second species, and we propose a simple mechanism to explain the stabilizing
      effect with respect to coalescence.

PMID- 15745000
TI  - Adsorption of oppositely charged polyelectrolyte/surfactant complexes at the
      air/water interface: formation of interfacial gels.
AB  - The adsorption and complexation of polystyrene sulfonate (a highly charged
      anionic polyelectrolyte) and dodecyltrimethylammonium bromide (a cationic
      surfactant) at the air-water interface can lead to interfacial gels that strongly
      influence foam-film drainage and stability. The formation and characteristics of
      these gels have been studied by combining surface tension, ellipsometry, and foam
      film drainage experiments. Simultaneously, the solution electromotive force is
      measured and used to track the polymer-surfactant interactions in the bulk
      solution. We find that surface gelation occurs above the critical aggregation
      concentration in solution but before bulk precipitation of the polymer-surfactant
      complexes. Furthermore, we reveal that strong readsorption of polymer-surfactant
      complexes occurs during the resolubilization of the precipitated complexes at
      high surfactant concentrations (i.e., >>critical micelle concentration).
      Seemingly overlooked in the past, this readsorption significantly influences the
      surface rheological properties and foam-film drainage of these systems.

PMID- 15745001
TI  - Fluorescence delineation of the surfactant microstructures in the CTAB-sOS-H2O
      catanionic system.
AB  - A key feature of amphiphilic molecules is their ability to undergo self-assembly,
      a process in which a complex hierarchical structure is established without
      external intervention. Ternary systems consisting of aqueous mixtures of cationic
      and anionic surfactants exhibit a rich array of self-assembled microstructures
      such as spherical and rodlike micelles, unilamellar and multilamellar vesicles,
      planar bilayers, and bicontinuous structures. In general, multiple complementary
      techniques are required to explore the phase behavior and morphology of aqueous
      systems of oppositely charged surfactants. As a novel and effective alternative
      approach, we use fluorescence spectroscopic measurements to examine the
      microstructures of aqueous cationic/anionic surfactant systems in the dilute
      surfactant region. In particular, we demonstrate that the polarity-sensitive
      fluorophore prodan can be used to demarcate the surfactant microstructures of the
      ternary system of cetyltrimethylammonium bromide, sodium octyl sulfate, and
      water. As the fluorescence signature of this probe is dependent on the nature of
      the surfactant aggregates present, our method is a promising new approach to
      effectively map complex surfactant phase diagrams.

PMID- 15745003
TI  - New protocol for oxidation in water: micellar oxidation systems composed of novel
      amphiphilic hydroperoxides.
AB  - A series of novel amphiphilic hydroperoxides, alpha-alkoxyalkyl hydroperoxides
      (alpha-AHPs) and their related hydroperoxides, were designed and prepared with
      the intention of developing new oxidizing agents bearing a micelle-forming
      character in water. After their fundamental physical and interfacial properties
      were elucidated, both oxidation of benzyl sulfide and epoxidation of geraniol
      promoted by these hydroperoxides were investigated in detail under various
      conditions. Effective oxidation ofbenzyl sulfide to the corresponding sulfoxide
      was achieved in aqueous micellar systems composed of alpha-AHPs la-d and a
      catalytic amount of MoO2(acac)2 at 30 degrees C. Up to 100% conversion was
      observed under the optimum conditions. In the case of epoxidation of geraniol in
      water, the corresponding 2,3-epoxide was selectively formed in good yields.
      Because the conversion of each substrate in the micellar systems was higher than
      that in nonmicellar media, the solubilization of substrates into micelles was
      certainly effective in promoting oxidations of insoluble substrates in aqueous
      media. Micellar oxidation systems composed of novel amphiphilic hydroperoxides
      afford a new protocol in order to derive safer conditions under which these
      reactions may be carried out.

PMID- 15745002
TI  - Structure and photophysical properties of porphyrin-modified metal nanoclusters
      with different chain lengths.
AB  - Three-dimensional porphyrin-monolayer-protected gold clusters with different
      chain lengths (MPCs) have been prepared to examine the structure and
      photophysical properties, in comparison with self-assembled monolayers (SAMs) of
      the porphyrins on a flat gold surface. The three-dimensional porphyrin MPCs
      exhibit electrochemical and photophysical properties that are much closer to
      those of a porphyrin reference compound in solution than those of two-dimensional
      porphyrin SAMs on the flat gold surface. The three-dimensional architectures of
      porphyrin MPCs with large surface area have improved the light-harvesting
      efficiency relative to the corresponding porphyrin SAM on the two-dimensional
      flat gold surface. Time-resolved single photon counting fluorescence and
      transient absorption spectroscopic studies have demonstrated that undesirable
      quenching of the porphyrin excited singlet state via energy transfer to the gold
      surface of the three-dimensional MPCs is much suppressed, as compared to the
      quenching of the porphyrin SAMs on the two-dimensional flat gold surface. Both
      the quenching rate constants of the porphyrin excited singlet state by the
      surfaces of bulk gold and gold nanoclusters reveal weak chain length dependence
      of the energy transfer quenching.

PMID- 15745004
TI  - Coalescence of particle-laden fluid interfaces.
AB  - Colloidal particles are capable of stabilizing emulsions and, thus, slowing or
      preventing their complete breakdown into phase-separated systems. Direct
      observations of the dynamics of such particles on both water and oil droplets are
      reported as two colloid-laden interfaces are brought into contact with each
      other. As coalescence proceeds, the complementary systems, representing oil-in
      water and water-in-oil emulsions, exhibit contrasting mechanisms for the
      formation of ring and disk structures by the particles as they serve to
      temporarily stabilize the approaching surfaces. An explanation of such behavior
      leads to a better understanding of the stabilization and breaking mechanisms of
      so-called Pickering emulsions.

PMID- 15745005
TI  - Optical and surface morphological properties of polarizing films fabricated from
      a chromonic dye by the photoalignment technique.
AB  - The inherent chromonic lyotropic liquid crystalline properties of a dye have been
      manipulated to fabricate multi-axial micropolarizing thin films by means of the
      photoalignment technique. The dye aqueous solution is deposited on a
      photopatterned polymer film to result in the macroscopic alignment of the dye
      molecules, followed by drying at ambient temperature. The solid polarizing dye
      layers thus produced exhibit very a high contrast ratio and degree of
      polarization in the region of visible light. Addition of a small amount of
      surfactant to the dye solution is a prerequisite for the generation of a nematic
      chromonic phase and for the formation of homogeneous thin dye layers on the
      polymer film. The correlation between the optical and surface morphological
      properties of the dye layers is discussed.

PMID- 15745006
TI  - Monitoring solute interactions with poly(ethylene oxide)-modified colloidal
      silica nanoparticles via fluorescence anisotropy decay.
AB  - The fluorescence-based nanosize metrology approach, proposed recently by Geddes
      and Birch (Geddes, C. D.; Birch, D. J. S. J. Non-Cryst. Solids 2000, 270, 191),
      was used to characterize the extent of binding of a fluorescent cationic solute,
      rhodamine 6G (R6G), to the surface of silica particles after modification of the
      surface with the hydrophilic polymer poly(ethylene oxide) (PEO) of various
      molecular weights. The measurement of the rotational dynamics of R6G in PEO
      solutions showed the absence of strong interactions between R6G and PEO chains in
      water and the ability of the dye to sense the presence of polymer clusters in 30
      wt % solutions. Time-resolved anisotropy decays of polymer-modified Ludox
      provided direct evidence for distribution of the dye between bound and free
      states, with the bound dye showing two decay components: a nanosecond decay
      component that is consistent with local motions of bound probes and a residual
      anisotropy component due to slow rotation of large silica particles. The data
      showed that the dye was strongly adsorbed to unmodified silica nanoparticles, to
      the extent that less than 1% of the dye was present in the surrounding aqueous
      solution. Addition of PEO blocked the adsorption of the dye to a significant
      degree, with up to 50% of the probe being present in the aqueous solution for
      Ludox samples containing 30 wt % of low molecular weight PEO. The addition of
      such agents also decreased the value and increased the fractional contribution of
      the nanosecond rotational correlation time, suggesting that polymer adsorption
      altered the degree of local motion of the bound probe. Atomic force microscopy
      imaging studies provided no evidence for a change in the particle size upon
      surface modification but did suggest interparticle aggregation after polymer
      adsorption. Thus, this redistribution of the probe is interpreted as being due to
      coverage of particles with the polymer, resulting in lower adsorption of R6G to
      the silica. The data clearly show the power of time-resolved fluorescence
      anisotropy decay measurements for probing the modification of silica surfaces and
      suggest that this method should prove useful in characterization of new
      chromatographic stationary phases and nanocomposite materials.

PMID- 15745007
TI  - Polyhedral oligomeric silsesquioxane amphiphiles: isotherm and brewster angle
      microscopy studies of trisilanolisobutyl-POSS at the air/water interface.
AB  - A trisilanol derivative of polyhedral oligomeric silsesquioxanes (POSS),
      trisilanolisobutyl-POSS, has recently been reported to form stable monolayers at
      the air/water interface. Moreover, the trisilanolisobutyl-POSS monolayer
      undergoes a nonequilibrium structural transition (collapse) around a surface
      pressure of Rho approximately 18 mN.m(-1). This paper explores the mono- and
      multilayer properties of POSS molecules at the air/water interface by the
      Wilhelmy plate technique and Brewster angle microscopy. Surface concentrations
      are controlled by four mechanisms: (1) compression at a constant rate, (2)
      stepwise compression followed by surface pressure relaxation to an "equilibrium"
      value, (3) successive additions of spreading solution followed by relaxation to a
      stable surface pressure value, and (4) hysteresis loops to test the reversibility
      of the structural transitions. Results show that both an increasing compression
      rate and a decreasing temperature lead to an increase in the surface pressure of
      the structural transition, which is consistent with the formation of solidlike
      multilayer domains during the collapse process. For the case of compression at a
      constant rate, small domains initially form and later aggregate to form large
      solid masses. Cessation of compression allows these large solid masses to relax
      into equilibrium ringlike structures with a lower surface pressure, Rho
      approximately 13 mN.m(-1). In contrast, if the film is expanded rapidly, these
      large solidlike domains relax into "spaghetti" like networks with a residual
      surface pressure that depends on the initial amount of the solidlike collapsed
      phase. Finally, successive addition and stepwise compression isotherm experiments
      lead to different and time-dependent morphologies. Understanding these surface
      properties of POSS molecules affords an excellent opportunity to design and study
      POSS/polymer blends for coating applications where POSS molecules with rigid
      inorganic cores, soft organic coronae, and dimensions comparable to polymeric
      monolayers can serve as perfectly monodisperse nanofillers.

PMID- 15745008
TI  - Atomic force microscopy of emulsion droplets: probing droplet-droplet
      interactions.
AB  - A method has been developed for attaching oil (tetradecane) droplets to the end
      of an atomic force microscopy (AFM) cantilever and for immobilizing droplets on a
      glass substrate. This approach has permitted the monitoring of droplet-droplet
      interactions in aqueous solution as a function of interdroplet separation.
      Coating the droplet surfaces with added proteins or surfactants has allowed the
      production of model emulsions. We demonstrate that AFM measurements of droplet
      deformability are sensitive to interfacial rheology by modifying the interfacial
      film on a pair of droplets in situ. For droplets coated with the anionic
      surfactant sodium dodecyl sulfate, screening of the double layer has been found
      to facilitate coalescence. Direct imaging of the droplets has revealed the
      presence of regularly spaced concentric rings on the droplet surfaces. Careful
      experimental studies suggest that these structures may be imaging artifacts and
      are not perturbations of the droplet surface determined by the composition of the
      interface.

PMID- 15745009
TI  - Oil coating on hydrophilic surfaces from emulsions and under shear flow.
AB  - We study the formation of silicone oil coating on negatively charged hydrophilic
      surfaces via emulsion deposition. Cationic surfactants usually adsorb and form
      bilayers onto negative surfaces. As a result, direct emulsions stabilized with
      cationic surfactants are paradoxically poorly efficient at coating negative
      substrates. We show in this work an alternative and new method, still based on
      electrostatic attractions, to coat negative substrates. Our method consists of
      using emulsions stabilized with nonionic surfactants and of adding to the oil
      cationic additives that are non-water-soluble and of high molecular weight to
      minimize their solubilization in the micelles formed by the neutral surfactant.
      The positively charged droplets stick efficiently onto the substrates. They form
      monolayer and uniform coatings. We study the kinetics and the density of the
      resulting coating using a flow cell experiment. This technique allows us to
      finely analyze the influence of several physicochemical parameters.

PMID- 15745010
TI  - Photoinduced adsorption of hydrogen and methane on gamma-alumina. the
      photoinduced chesorluminescence (PhICL) effect.
AB  - Adsorption of hydrogen and methane on a preirradiated surface of gamma-Al2O3
      produces an afterglow, which has been described as a photoinduced
      chesorluminescence (PhICL), whose spectral features identify with the intrinsic
      photoluminescence of alumina. The emission spectrum consists of at least four
      overlapping single emission bands. For methane adsorption, the PhICL phenomenon
      is seen only if the solid is preirradiated in the presence of oxygen. Emission
      decay kinetics of the PhICL effect for gamma-Al2O3 reveal two wavelength regimes:
      a short wavelength regime at lambda = 300-370 nm (decay time tau = 1.1 +/- 0.2 s;
      signal width = 2.8 s), and a longer wavelength regime at lambda = 380-700 nm
      (decay time tau = 2.1 +/- 0.1 s; signal width = 4.3 s). A model is proposed in
      which there exist two different emission centers and, thus, two different
      pathways for emission decay. In the first, emission originates with electron
      trapping by such deep energy traps as anion vacancies {e- + Va --> F+ + hv1} to
      yield electron F-type color centers, whereas in the second, emission originates
      from electron/trapped hole recombination {e- + Os*- --> Os2- + hv2}. The first
      common step of the pathways is homolytic dissociative chemisorption of hydrogen
      and methane upon interaction with surface-active hole centers Os*-, produced upon
      preirradiation of alumina, to give atomic hydrogen H* and methyl radicals CH3*.
      Thermoprogrammed desorption spectra of photoadsorbed or postsorbed oxygen show
      that adsorbed oxygen interacts with atomic hydrogen and methyl radicals. The
      products of thermodesorption were H2O for hydrogen and H2O, CO2, and CH3CH3 for
      methane. The Solonitsyn memory effect coefficient was also evaluated for oxygen
      photoadsorption.

PMID- 15745011
TI  - Application of electrochemical impedance spectroscopy to the study of dioleoyl
      phosphatidylcholine monolayers on mercury.
AB  - Electrochemical impedance spectroscopy has been applied to the analysis of the
      behavior of monolayers of dioleoyl phosphatidylcholine (DOPC) on a mercury
      electrode. Experiments were carried out in electrolytes KCl and NaCl (0.1 mol dm(
      3)) and Mg(NO3)2 (0.05 mol dm(-3)), and the frequency dependence of the complex
      impedance was estimated between 65 000 and 0.1 Hz at potentials -0.4 to -1.5 V
      versus Ag/AgCl 3.5 mol dm(-3) KCl at uncoated and coated electrode surfaces.
      Experiments were also carried out in the presence of gramicidin A (gA). Between
      the potentials of -0.4 and -0.7 V, the DOPC monolayer behaves as an almost ideal
      capacitor with little frequency dispersion. At more negative potentials, the
      impedance data show the formation of defects (-0.7 to -0.85 V), ingression of
      electrolyte into the layer (capacitance peak approximately -0.935 V),
      reorientation of phospholipid-water structures (capacitance peak approximately 
      1.0 V), and initiation of phospholipid desorption (approximately -1.3 V). gA
      interaction with the phospholipid monolayer at -0.4 V is shown as an additional
      low-frequency element. A general "one capacitor model" in a RC series equivalent
      circuit is developed incorporating the frequency dispersion of the capacitance,
      distribution of the time constants of the dispersion, and a coefficient related
      to the interface between the solution and the coated electrode. This latter
      coefficient is the most robust and decreases at potentials approaching those
      coincident with the DOPC phase transitions.

PMID- 15745012
TI  - Quantification of fluorine density in the outermost atomic layer.
AB  - The outermost atomic layer of perfluorinated thiol monolayers on gold and
      poly(tetrafluoroethylene) (PTFE) is analyzed by low-energy ion scattering.
      Absolute quantification of fluorine density in this layer was achieved after
      calibrating the fluorine signal with a freshly cleaved LiF(100) single crystal.
      The fluorine density of monolayers of a C8F17-thiol on gold was 1.48 x 10(15) F
      atoms/cm2, whereas for PTFE a value of 1.24 x 1015 F atoms/cm2 was observed. This
      difference was explained by the different tilt angles of the thiol on gold and
      PTFE chains with respect to the surface normal. Both a configurational and a
      molecular interpretation on the perfluorinated thiol monolayer on gold are given.

PMID- 15745013
TI  - Adsorption of liquid-phase alkane mixtures in silicalite: simulations and
      experiment.
AB  - A combination of experimental and computational studies of adsorption from liquid
      phase mixtures of linear alkanes in the zeolite silicalite is presented here.
      Configurational biased grand canonical Monte Carlo simulations combined with
      identity-swap moves are used to equilibrate the simulations in reasonable times.
      Interesting trends observed in experiments have been captured quantitatively by
      simulations. A siting analysis of the simulation data reveals that, during
      adsorption from a liquid mixture, shorter alkanes prefer the zigzag channels and
      longer alkanes concentrate in the straight channels of silicalite.

PMID- 15745014
TI  - Polyetheretherketone (PEEK) surface functionalization by low-energy ion-beam
      irradiation under a reactive O2 environment and its effect on the PEEK/copper
      adhesives.
AB  - A low-energy Ar+ ion beam was used to modify the surface of a
      polyetheretherketone (PEEK) film. The modification reaction proceeded with or
      without oxygen gas injected during the irradiation. The surface functional groups
      of the modified PEEK were confirmed with X-ray photoelectron spectroscopy as
      increasing various oxygen-containing functional groups. The concentration of the
      functional groups varied rapidly with the irradiation time, reached a maximum
      value, and then slowly decreased. The surface morphology of PEEK was
      substantially changed by ion-beam irradiation. Surface smoothening occurred so
      that the surface roughness reached almost constant value after some irradiation
      time. The incorporation of functional groups on the PEEK surface and the surface
      topology change had opposite effects on the adhesion strength between PEEK and
      copper. Dominance of the former was evident because the lap-shear strength
      initially increased with the irradiation. The special surface features
      significantly enhanced the adhesion strength between the evaporated copper layer
      and the modified PEEK surface. However, the decrease in the surface roughness
      with a long time irradiation implies a decrease in adhesion strength due to a
      smaller contact area, and the shear strength due to topology change also slowly
      decreased after a long time irradiation.

PMID- 15745015
TI  - Rupture of wetting films caused by nanobubbles.
AB  - It is now widely accepted that nanometer sized bubbles, attached at a hydrophobic
      silica surface, can cause rupture of aqueous wetting films due to the so-called
      nucleation mechanism. But the knowledge of the existence of such nanobubbles does
      not give an answer to how the subprocesses of this rupture mechanism operate. The
      aim of this paper is to describe the steps of the rupture process in detail: (1)
      During drainage of the wetting film, the apex of the largest nanobubble comes to
      a distance from the wetting film surface, where surface forces are acting. (2) An
      aqueous "foam film" in nanoscale size is formed between the bubble and the
      wetting film surface; in this foam film different Derjaguin-Landau-Verwey
      Overbeek (DLVO) forces are acting than in the surrounding wetting film. In the
      investigated system, hydrophobized silica/water/air, all DLVO forces in the
      wetting film are repulsive, whereas in the foam film the van der Waals force
      becomes attractive. (3) The surface forces over and around the apex of the
      nanobubble lead to a deformation of the film surfaces, which causes an additional
      capillary pressure in the foam film. An analysis of the pressure balance in the
      system shows that this additional capillary pressure can destabilize the foam
      film and leads to rupture of the foam film. (4) If the newly formed hole in the
      wetting film has a sufficient diameter, the whole wetting film is destabilized
      and the solid becomes dewetted. Experimental data of rupture thickness and
      lifetime of wetting films of pure electrolyte and surfactant solutions show that
      the stabilization of the foam film by surfactants has a crucial effect on the
      stability of the wetting film.

PMID- 15745016
TI  - Binding of amino acids to "smart" sorbents: where does hydrophobicity come into
      play?
AB  - Poly(N-isopropylacrylamide) (PNIPA)-based sorbents have been successfully used as
      sorbents in temperature-sensitive chromatography. Yet, the mechanisms controlling
      the binding of biochemicals to these sorbents and, therefore, the separation
      process are not fully understood. In the current work, the role of hydrophobic
      interactions in the binding of amino acids of different hydrophobicities to PNIPA
      microgels was studied. Binding experiments were conducted both below (25 degrees
      C) and above (37 degrees C) the volume-phase transition temperature of the gel.
      At 25 degrees C, no straightforward correlation between the partition coefficient
      and the hydrophobicity could be suggested for low hydrophobicity values.
      Contrary, at higher hydrophobicities the partition coefficient increases with
      increasing hydrophobicity. This correlation holds for the whole hydrophobicity
      range at 37 degrees C; however, the binding data suggests two different binding
      mechanisms of the hydrophilic amino acids and the hydrophobic ones. Isothermal
      titration calorimetry measurements confirmed this suggestion: The binding of
      hydrophobic amino acids seems to be driven by hydrophobic interactions, as
      evident from the positive binding enthalpy and the clear correlation between the
      amino acid's hydrophobicity and the binding entropy. Contrary, the binding of the
      hydrophilic amino acids was exothermic, implying a binding mechanism based on
      specific interactions, most probably hydrogen bonding.

PMID- 15745018
TI  - Physical and electrochemical characterizations of microwave-assisted polyol
      preparation of carbon-supported PtRu nanoparticles.
AB  - PtRu nanoparticles supported on Vulcan XC-72 carbon and carbon nanotubes were
      prepared by a microwave-assisted polyol process. The catalysts were characterized
      by transmission electron microscopy, X-ray diffraction, and X-ray photoelectron
      spectroscopy (XPS). The PtRu nanoparticles, which were uniformly dispersed on
      carbon, were 2-6 nm in diameter. All PtRu/C catalysts prepared as such displayed
      the characteristic diffraction peaks of a Pt face-centered cubic structure,
      excepting that the 2theta values were shifted to slightly higher values. XPS
      analysis revealed that the catalysts contained mostly Pt(0) and Ru(0), with
      traces of Pt(II), Pt(IV), and Ru(IV). The electro-oxidation of methanol was
      studied by cyclic voltammetry, linear sweep voltammetry, and chronoamperometry.
      It was found that both PtRu/C catalysts had high and more durable
      electrocatalytic activities for methanol oxidation than a comparative Pt/C
      catalyst. Preliminary data from a direct methanol fuel cell single stack test
      cell using the Vulcan-carbon-supported PtRu alloy as the anode catalyst showed
      high power density.

PMID- 15745017
TI  - Phase dependent electrochemical properties of polar self-assembled monolayers
      (SAMs) modified via the fusion of mixed phospholipid vesicles.
AB  - Unilamellar vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and
      varying quantities of either 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1
      glycerol) (sodium salt) (DMPG) or 1,2-dimyristoyl-3-trimethylammonium-propane
      (chloride salt) (DMTAP) were used to deposit lipid bilayer assemblies on self
      assembled monolayers (SAMs) on gold. The supporting SAMs in turn were composed of
      ferrocene-functionalized hexadecanethiol chains (FcC16SH) diluted to low coverage
      in 1-hydroxylhexadecanethiol (HOC16SH) or a single-component monolayer phase of
      the latter. The mass coverages of the DMPC/DMPG layers deposited in this way were
      measured using surface plasmon resonance (SPR) and found to decrease with an
      increasing content of DMPG in the vesicles. The SPR data show that the lipid
      assembly, while stable with respect to gentle rinsing in aqueous buffer, is
      reversible and the lipid adlayer is removable by immersion in a solvent such as
      ethanol. The effects of the adsorbed lipid layer on the electrochemical
      interactions of the hybrid lipid/SAM with several redox probes [e.g., K4Fe(CN)6,
      Ru(NH3)6Cl3, and CsHsFe-[(C5H4CH2N+H(CH3)2] were characterized using cyclic
      voltammetry (CV). At a composition of 5% DMPG in DMPC, the permeabilities of the
      probes through the lipid layer were affected significantly relative to that
      observed with a pure DMPC layer. These effects include a striking observation of
      an enhanced, ionic-charge-specific molecular discrimination of the
      electrochemical probes. At higher concentrations of the DMPG, significant
      permeation of the lipid adlayer was seen for all the probes. These latter changes
      are also attended by a significant increase in the capacitive currents measured
      in CV experiments as compared to those observed for either a pure SAM or one
      modified by only DMPC. This effect likely results from the influence of the
      charged lipid on the diffuse Gouy-Chapman electrolyte layer at the SAM interface.
      In contrast to the behaviors seen with DMPG, the incorporation of DMTAP into the
      adsorbed DMPC had no impact on the permeation of the adlayer by soluble redox
      probes as judged by the observed electrochemistry, a result that appears to
      correlate with a less ideal mixing of lipids in the DMPC/DMTAP system relative to
      that of a DMPC/DMPG mixture.

PMID- 15745019
TI  - Viscoelasticity of gelatin surfaces probed by AFM noise analysis.
AB  - The viscoelastic properties of surfaces of swollen gelatin were investigated by
      analyzing the Brownian motion of an atomic force microscopy (AFM) cantilever in
      contact with the gel surface. A micron-sized glass sphere attached to the AFM
      cantilever is used as the dynamic probe. When the sphere approaches the gelatin
      surface, there is a static repulsive force without a jump into contact. The
      cantilever's Brownian movement is monitored in parallel, providing access to the
      dynamic sphere-surface interaction as quantified by the dynamic spring constant,
      kappa, and the drag coefficient, xi. Gelatin is used as a model substance for a
      variety of other soft surfaces, where the stiffness of the gel can be varied via
      the solvent quality, the bloom number, and the pH. The modulus derived from the
      static force-distance curve is in the kPa range, consistent with the literature.
      However, the dynamic spring constant as derived from the Brownian motion is much
      larger than the static differential spring constant dF/dz. On retraction, one
      observes a rather strong adhesion hysteresis. The strength of the bridge (as
      given by the dynamic spring constant and the drag coefficient) is very small.

PMID- 15745020
TI  - Preparation of nanosized ZnS-passivated CdS particle films via the MOCVD process
      with co-fed single source precursors.
AB  - A novel approach was developed to prepare thin films of nanosized ZnS-passivated
      CdS particles via a metal-organic chemical vapor deposition (MOCVD) process with
      co-fed single source precursors of CdS and ZnS. Single source precursors of CdS
      and ZnS with sufficiently different reactivity, as judged from thermogravimetry
      analysis, were prepared and paired up to form ZnS-passivated CdS, (CdS)ZnS, and
      CdS-modified ZnS, (ZnS)CdS, particle films in a one-step process. For comparison
      purposes, sequential layer growth of CdS/ZnS and ZnS/CdS particle films was also
      conducted, and single compound particle films were prepared. These films were
      characterized with absorption spectrometry, photoluminescence spectroscopy,
      scanning electron microscopy, and powder X-ray diffraction spectra. The
      photoluminescence efficiency of the resulting composite particle film of ZnS
      passivated CdS was significantly enhanced as compared to that of the plain CdS
      film, due to the effective passivation of surface electronic states of CdS by
      ZnS, a material with a higher conduction band than that of CdS. As for particle
      films of CdS-modified ZnS, a decay in photoluminescence efficiency was observed.
      The enhancement or decay in photoluminescence efficiency was much more pronounced
      for the passivated and modified system than for the sequential layer system,
      proportional to the interfacial area between the CdS and ZnS phases.

PMID- 15745021
TI  - Enhanced electrorheology of conducting polyaniline confined in MCM-41 channels.
AB  - A composite material of a silica-based mesoporous molecular sieve, MCM-41, with
      conducting polyaniline (PANI) inside the uniformly aligned one-dimensional
      channels (PANI/MCM-41) was prepared and its nanocomposite formation was confirmed
      through an electrical conductivity measurement. This nanocomposite particle was
      adopted for a dispersed phase in electrorheological (ER) fluids, and the ER
      property was measured using a Couette-type rotational rheometer equipped with a
      high voltage generator. Suspension of PANI/MCM-41 showed ER properties more
      enhanced than those of MCM-41 or PANI alone as a result of the anisotropic
      polarization of the PANI/MCM-41 nanocomposite.

PMID- 15745022
TI  - Study of support effects on the reduction of Ni2+ ions in aqueous hydrazine.
AB  - We have studied the effect of silica of quartz-type on the reducibility of nickel
      acetate in aqueous hydrazine (80 degrees C, pH = 10-12) and metal particle
      formation. The obtained materials were characterized by X-ray diffraction,
      transmission electron microscopy, and thermodesorption experiments. With nickel
      acetate alone, the reduction was partial (45%) and a metal film at the liquid-gas
      interface or a powdered metal precipitate with an average particle size of 120 nm
      was obtained. In the presence of silica as the surfactant, the reduction of
      nickel acetate was total and the nickel phase deposited as a film on the support
      with an average particle size of 25 nm. Supported nickel acetate was also totally
      reduced. Crystallites of a mean particle size of about 3 nm were obtained.
      Decreasing the nickel content or increasing the hydrazine/nickel ratio decreased
      the metal particle size. Whiskers were formed for low nickel loadings. Hydrogen
      thermal treatment of the reduced phase showed that the organic acetate fragment,
      belonging to the precursor salt, still remained strongly attached to the nickel
      phase. The amount of the retained organic matrix depended on the metal particle
      size. Surface defects are suggested as active sites, which enhanced nickel ion
      reduction in the presence of silica as the surfactant or support. Metal-support
      interactions and the nucleation/ growth rate were the main factors determining
      the size and morphology of the supported metal particles formed. The organic
      matrix covered the reduced nickel phase.

PMID- 15745023
TI  - Size-controlled synthesis and growth mechanism of monodisperse tellurium nanorods
      by a surfactant-assisted method.
AB  - This article describes a surfactant-assisted approach to the size-controlled
      synthesis of uniform nanorods of trigonal tellurium (t-Te). These nanorods were
      grown from a colloidal dispersion of amorphous Te (a-Te) and t-Te nanoparticles
      at room temperature, which was first formed through the reduction of (NH4)2TeS4
      by Na2SO3 in aqueous solution at 80 degrees C. Nuclei formed in the reduction
      process had a strong tendency to grow along the [001] direction due to the
      inherently anisotropic structure of t-Te. The formation of Te nanorods could be
      ascribed to the confined growth through the surfactant adsorbing on the surfaces
      of the growing Te particles. By employing various surfactants in the synthesis
      system, Te nanorods with well-controlled diameters and lengths could be
      reproducibly produced by this method. Both the diameters and lengths of nanorods
      decreased with the increase of the alkyl length and the polarity of the
      surfactants. Te nanorods could also be obtained in mixed surfactants, where the
      different surfactants were used to selectively control the growth rates of
      different crystal planes. We also observed that the as-synthesized nanorods with
      uniform size could be self-assembled into large-area smecticlike arrays.

PMID- 15745024
TI  - Electrochemical polymerization of aniline monomers infiltrated into well-ordered
      truncated eggshell structures of polyelectrolyte multilayers.
AB  - The use of nanosphere lithography to construct two-dimensional arrays of
      polystyrene (PS) particles coated with multilayered polyelectrolyte (PE) shells
      and truncated eggshell structures composed of PE thin layers is reported. The
      truncated eggshell PE structures were produced by extraction of the PS particle
      cores with toluene. The core-extraction process ruptures the apex of the PE
      coating and causes a slight expansion of the PE thin layers. Aniline
      hydrochloride was infiltrated into the PE shells and subsequently
      electropolymerized to yield an array of a composite containing polyaniline (PAni)
      and PE thin shells. Voltammetric, quartz crystal microbalance, and reflectance
      Fourier transform infrared spectroscopic measurements indicate that aniline
      monomers were confined within the thin PE shells and the electropolymerization
      occurred in the interior of the PE shell. The PE thickness governs the amount of
      infiltrated monomer and the ultimate loading of the PAni in the truncated
      eggshell structure. Surface-structure imaging by atomic force microscopy and
      scanning electron microscopy, carried out after each step of the fabrication
      process, shows the influence of the PE thickness on the organization and
      dimensions of the arrays. Thus, the PE thin shells composed of different layers
      can function as nanometer-sized vessels for the entrapment of charged species for
      further construction of composite materials and surface modifications. This
      approach affords a new avenue for the synthesis of new materials that combine the
      unique properties of conductive polymers and the controllability of template
      directed surface reactions.

PMID- 15745025
TI  - Planarizing surface topography by polymer adhesion to water-soluble templates
      with replicated null pattern.
AB  - Water-soluble polymer templates are replicated from flat master surface patterns
      by spin-casting a poly(vinyl alcohol) film-forming solution that solidifies at
      standard ambient conditions in less than 1 min. The fabricated water-soluble
      templates are coupled to substrates with surface topography by polymer adhesion
      with an intervening reactive or photocurable liquid layer. After curing, the
      resulting two-layer solid structure is subjected to water thereby dissolving the
      soluble template to expose the underlying polymer adhesive layer with flat
      surface topography. The results demonstrate a reduction of surface topography
      from several micrometers to less than 100 nm. The chemical interactions involved
      in bonding the soluble template to the polymer adhesive and then dissolving are
      measured by Raman spectroscopy to demonstrate that the constituents comprising
      the water-soluble template are absent from the surface of the planarization
      material.

PMID- 15745026
TI  - Photocatalytic activity of SrTiO3 codoped with nitrogen and lanthanum under
      visible light illumination.
AB  - Yellow SrTiO3 powders codoped with nitrogen and lanthanum (STO:N,La) were studied
      as visible light photocatalysts. The crystal phase of STO:N,La exhibited a pure
      perovskite phase, and O and Sr sites atoms were substitutionally doped with N and
      La atoms, respectively. The first principle calculation of STO:N,La indicated
      that the edge of the N(2p) band is situated above the valence band, which
      consisted of O(2p) orbitals, and the La orbitals did not exist in the band gap of
      SrTiO3. STO:N,La exhibited a higher oxidation activity of gaseous 2-propanol
      under vis illumination than SrTiO3 doped only with nitrogen (STO:N). The high
      activity of STO:N,La was due to the decrease in the oxygen vacancies, which acted
      as electron-hole recombination centers, because codoping with La3+ and N3- ions
      maintained the charge balance. The optimum doping density of N and La for visible
      light activity was 0.5%, and STO:N,La(0.5%) had an activity under UV illumination
      similar to pure SrTiO3.

PMID- 15745027
TI  - Preparation of PAMAM- and PPI-metal (silver, platinum, and palladium)
      nanocomposites and their catalytic activities for reduction of 4-nitrophenol.
AB  - Dendrimer-metal (silver, platinum, and palladium) nanocomposites are prepared in
      aqueous solutions containing poly(amidoamine) (PAMAM) dendrimers with surface
      amino groups (generations 3, 4, and 5) or poly(propyleneimine) (PPI) dendrimers
      with surface amino groups (generations 2, 3, and 4). The particle sizes of the
      metal nanoparticles obtained are almost independent of the generation as well as
      the concentration of the dendrimer for both the PAMAM and the PPI dendrimers; the
      average sizes of silver, platinum, and palladium nanoparticles are 5.6-7.5, 1.2
      1.6, and 1.6-2.0 nm, respectively. It is suggested that the dendrimer-metal
      nanocomposites are formed by adsorbing the dendrimers on the metal nanoparticles.
      Studies of the reduction reaction of 4-nitrophenol by these nanocomposites show
      that the rate constants are very similar between PAMAM and PPI dendrimer-silver
      nanocomposites, whereas the rate constants for the PPI dendrimer-platinum and 
      palladium nanocomposites are greater than those for the corresponding PAMAM
      dendrimer nanocomposites. In addition, it is found that the rate constants for
      the reduction of 4-nitrophenol involving all the dendrimer-metal nanocomposites
      decrease with an increase in the dendrimer concentrations, and the catalytic
      activity of dendrimer-palladium nanocomposites is highest.

PMID- 15745028
TI  - Instability, dynamics, and morphology of thin slipping films.
AB  - Based on the linear stability and nonlinear simulations, we show that the surface
      instability, dynamics, and morphology of supported thin liquid films are
      profoundly altered by the presence of slippage on the substrate. A general
      dispersion equation for flow in slipping thin films is derived and simplified to
      identify three different regimes of slippage (weak, moderate, and strong) and
      obtain the length and time scales of instability in them. For illustration, the
      ubiquitous van der Waals interactions have been employed. Different regimes of
      slip-flow can be predicted based on a nondimensional parameter, xi, which is a
      function of slip length, film thickness, intermolecular potential, and
      interfacial tension. Two distinct transitions from weak to moderate slip and from
      moderate to strong slip occur at xiT1 approximately 0.01 and xiT2 approximately
      500, respectively. More specifically, a decrease in film thickness causes
      transitions from weak to moderate to strong slip regime. Even a weak slippage
      causes faster breakup of a thin film, whereas slippage beyond a transition value
      (slip length, bT1) increases the length scale of instability and reduces the
      number density of holes compared to the nonslipping case. Strong slippage
      produces holes faster, and the holes are fewer in number and have less developed
      rims. The exponents for the length scale (lambdam infinity h0n; h0 is film
      thickness) and time scale of instability (tr infinity h0m) change
      nonmonotonically with slippage (for nonretarded van der Waals instability, n E
      (1.25, 2), m E (3, 6)). Retardation in van der Waals potential increases the
      exponents (n E (1.5, 2.5), m E (5, 8)). The initial stage of evolution of a
      slipping film, simulated based on nonlinear equations, follows the length scale
      and time scale of instability, close to the prediction of linear analysis. It is
      hoped that the present analysis will help in better interpretation of thin film
      experiments, in estimation of slippage, and in the determination of
      intermolecular forces from the length and time scales of the instability.

PMID- 15745029
TI  - Investigation of the microstructure of micelles formed by hard-sphere chains
      interacting via size nonadditivity by discontinuous molecular dynamics
      simulation.
AB  - Micelle formation by short nonadditive hard surfactant chains was investigated at
      different size ratios, reduced densities, and nonadditivity parameters using
      molecular dynamics simulation. It was found that spherical, cylindrical,
      lamellar, and reverse micelles can form in systems with different head, tail, and
      solvent characteristics. Hard-core surfactant chains composed of a head segment
      and three tail segments were simulated in a solvent of hard spheres. The
      formation of micelles was found to be a strong function of the packing fraction
      and nonadditivity parameter. Micelles were more stable at higher densities and
      larger nonadditivity parameters. At lower densities, micelles tended to break
      into small, dynamic globules.

PMID- 15745030
TI  - Surface oxidation states in Si/SiO2 nanostructures prepared from Si/SiO2
      mixtures.
AB  - Silica nanospheres have been produced by a novel technique where surface Si
      oxidation states can be adjusted using the ratio of metalloid ions/metalloid
      atoms in the starting mixture. When the proportions of Si4+/Si0 are equal in the
      synthesis, the resulting solid is considerably more reactive than Cab-O-Sil
      toward the phenol hydroxylation reaction and the surface shows an average Si
      oxidation state of +3. On the other hand, those silica nanospheres, produced from
      a mixture of Si4+/Si0 = 0.25, showed a lower reactivity comparable to that of Cab
      O-Sil which XPS demonstrates has a surprisingly low average Si oxidation state
      close to +1. We speculate that the silicon surface oxidation state and the number
      of surface silanol groups play important roles in determining the activity of the
      solid toward the phenol hydroxylation reaction. In expanding our earlier report4
      on the copper-silica system, we establish that the surface chemistry of the
      silica nanospheres is apparently different from that of fumed, amorphous silica.
      These results suggest that we are developing a technique that can be generalized
      to create supported, mixed metal oxides having tunable average surface oxidation
      states.

PMID- 15745031
TI  - Synthesis of novel metal sulfide-polymer composite microspheres exhibiting
      patterned surface structures.

PMID- 15745032
TI  - Colloidal crystals of silica-homopolypeptide composite particles.

PMID- 15745033
TI  - Immobilization strategy and characterization of hydrogel-based thin films for
      interrogation of ligand binding with staphylococcal enterotoxin B (SEB) in a
      protein microarray format.

PMID- 15745034
TI  - KHCO3 mineralization self-assembled on aminopropyl organosilica.

PMID- 15745035
TI  - Evidence-based experience management in health care.

PMID- 15745036
TI  - Hospitals need better pricing strategies.

PMID- 15745037
TI  - Identity theft case creates new HIPPA concerns for hospitals.

PMID- 15745038
TI  - United Surgical Partners grows with hospital, physician partners.

PMID- 15745039
TI  - Symbion grows into chain of 51 surgery centers in 20 states.

PMID- 15745041
TI  - Cleveland clinic, McDonald's dispute creates questions for hospitals.

PMID- 15745040
TI  - Most hospitals stick with policies on post c-section c-sections.

PMID- 15745042
TI  - Hospitals face new generation of medical staff challenges.

PMID- 15745043
TI  - Past and present vaccine development strategies for the control of foot-and-mouth
      disease.
AB  - Foot-and-mouth disease (FMD) virus (FMDV) was the first animal virus to be
      identified. Since then, it has become a model system in animal virology and more
      information has been obtained about FMDV. The disease causes heavy economic
      crises in enzootic countries both due to loss of animal health and productivity.
      The only way of its control in an enzootic area is strict vaccination and
      restricted animal movement. The first experimental vaccine against FMD was made
      in 1925 using formaldehyde inactivation of cattle tongue infected with the virus
      and this approach remained the basic one until late 1940s. Antigenic plurality
      and continuous co-circulation of different serotypes in a given geographical
      region and persistence of virus in infected or vaccinated animals make the
      disease very difficult to control. The latter is solely based upon the
      application of isolation, slaughter or aphtisation, and vaccination. With the
      advent of recombinant DNA technology, recombinant protein and/or DNA-based
      vaccines are being tested in various heterologous systems for development of FMD
      vaccines. The subunit vaccines, synthetic peptide vaccines, DNA vaccines,
      cytokine-enhanced DNA vaccines, recombinant empty capsid vaccines, chimeric viral
      vaccines, genetically engineered attenuated vaccines, recombinant viral vector
      vaccines, self-replicating genetic vaccines and transgenic plants with expressed
      FMDV proteins represent the present vaccine development strategies for control of
      FMD.

PMID- 15745044
TI  - Prospects for hepatitis C vaccine.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and
      hepatocellular carcinoma worldwide. Unfortunately, neither a vaccine nor any
      effective therapy is available. Efforts are now directed towards the development
      of an effective vaccine besides chemotherapy. This review briefly summarizes the
      properties of an effective vaccine for the control of HCV infection. The
      mechanisms of protective immune response induced by HCV are not well understood.
      It is presumed that humoral and cellular immune responses play an important role.
      Even though there are various obstacles in the development of HCV vaccine, we
      describe a few promising approaches such as DNA vaccine, recombinant virus
      vaccine, HCV-like particles (HCV-LPs), peptide-based vaccine and plant-derived
      recombinant subunit vaccine.

PMID- 15745045
TI  - Isolation of bovine viral diarrhea virus 1, a pestivirus from autopsied lamb
      specimen from Tamil Nadu, India.
AB  - An epizootic of febrile illness among the Madras red breed of sheep had occurred
      in 1994 in Verrapuram, Chennai, India. The epizootic was suspected as Rift Valley
      fever (RVF)-like sickness based on clinical features. However, its etiological
      agent could neither be isolated nor implicated conclusively. During the post
      epizootic period a male lamb died of similar clinical features and the spleen was
      immediately collected. Inoculation of spleen suspension in infant mouse brain
      yielded a virus that was serially passaged in infant mice and rhabdomyosarcoma
      (RD) cells. Electron microscopic observations revealed virus particles resembling
      flaviviruses. RT-PCR performed on extracted total RNA from infected cells and
      mouse brains with flavivirus-specific or RVF-specific primers gave negative
      results. However, an amplicon of 280 bp was obtained with pestivirus-specific
      primers from the 5'-UTR. Further, a nested PCR yielded a product of 157 bp.
      Nucleotide sequencing of the 157 bp product showed 100% homology to BVDV-1.
      Western blot analysis with a flavivirus envelope protein-specific MAb revealed
      three proteins of 33 K, 45 K and 55 K. Further studies suggested that the 33 K
      and 55 K proteins were glycosylated. This is the first report of isolation of
      BVDV-1 from a lamb in India.

PMID- 15745046
TI  - Molecular characterization of a strain of cucumber mosaic virus based on coat
      protein and movement protein genes.
AB  - Cucumber mosaic virus (CMV) A strain (CMV-A) isolated from Amaranthus tricolor
      was partially characterized at molecular level. Complete coat protein (CP) and
      movement protein (MP) ORFs were cloned and sequenced. The 657 bp region of CP
      gene and the 840 bp region of MP gene encode 218 and 276 amino acids,
      respectively. CP, at nucleotide level, showed 90-98% sequence identity with the
      CMV subgroup I and less than 80% with the CMV subgroup II, it showed at amino
      acid level 92-96% identity with the subgroup I and 74-87% with the subgroup II.
      The nucleotide and amino acid sequence identities of MP ranged in 91-94% and 92
      96%, respectively with the subgroup I but in 81-83% with the subgroup II.
      Phylogenetic trees generated from nucleotide and amino acid sequences of both CP
      and MP genes identified the virus strain as a member of the subgroup IB. CMV-A CP
      also displayed a remarkably higher homology with Indian strains of CMV than with
      other CMV strains and formed a separate cluster within the subgroup IB.

PMID- 15745047
TI  - Antitumor activity of bacteriophages in murine experimental cancer models caused
      possibly by inhibition of beta3 integrin signaling pathway.
AB  - Bacteriophages (phages) as bacterial viruses are generally believed to have no
      intrinsic tropism for mammalian cells. In this study the interactions between
      phages and various eukaryotic cells were investigated. Binding of phages to the
      membranes of cancer and normal blood cells was observed. Moreover, it was shown
      that the wild-type phage T4 (wtT4) and its substrain HAP1 with enhanced affinity
      for melanoma cells inhibit markedly and significantly experimental lung
      metastasis of murine B16 melanoma cells by 47% and 80%, respectively. A possible
      molecular mechanism of these effects, namely a specific interaction between the
      Lys-Gly-Asp motif of the phage protein 24 and beta3-integrin receptors on target
      cells is proposed. It was also shown that anti-beta3 antibodies and synthetic
      peptides mimicking natural beta3 ligands inhibit the phage binding to cancer
      cells. This is in line with the well-described beta3 integrin-dependent mechanism
      of tumor metastasis. It is concluded that the blocking of beta3 integrins by
      phage preparations results in a significant decrease in tumor invasiveness.

PMID- 15745048
TI  - Development of a N gene-based PCR-ELISA for detection of Peste-des-petits
      ruminants virus in clinical samples.
AB  - A highly sensitive N gene-based PCR-ELISA for the detection of Peste-des-petits
      ruminants virus (PPRV) was developed. The RT-PCR yielded a digoxigenin (DIG)
      labeled product of 336 bp comprising a sequence from PPRV N gene, which was then
      detected by ELISA. The assay could detect the viral RNA in PPRV-infected tissue
      culture fluids with a titer as low as 0.1 TCID(50)/ml. The assay is 10,000 times
      more sensitive than a classical RT-PCR combined with agarose gel electrophoresis.
      The assay could detect the virus in the clinical samples, which were negative by
      conventional sandwich ELISA (S-ELISA). The percentage positivity of the assay in
      detecting the virus in clinical samples was 66.2% compared to 48.6% for S-ELISA.
      The assay was more sensitive than S-ELISA also in detecting the virus in early as
      well as late phases of the disease. In addition, the assay could also be used for
      differential diagnosis of PPRV and Rinderpest virus (RPV).

PMID- 15745049
TI  - Properties of a virus isolated from Vernonia amygdalina Del. in Lagos, Nigeria.
AB  - A previously uncharacterized virus tentatively named Vernonia green vein-banding
      virus (VGVBV) was isolated from Vernonia amygdalina Del. ("bitterleaf") from
      Lagos, Nigeria. The virus was mechanically transmissible but had a narrow host
      range restricted to Nicotiana benthamiana, Chenopodium quinoa and C.
      amaranticolor. It was also transmissible in a non-persistent manner by Myzus
      persicae. The virus was purified from N. benthamiana and about 750 nm long
      flexuous rod-shaped particles were observed in purified preparations as well as
      in leaf-dips of Vernonia sp. Inclusion bodies in the form of pinwheels and
      scrolls were observed in ultrathin sections of Vernonia leaves by electron
      microscopy. M(r), of the viral coat protein was estimated to be about 34 K. In
      indirect ELISA, all 20 samples from naturally infected Vernonia sp. reacted
      positively with a potyvirus-specific monoclonal antibody (MAb) as well as with an
      antiserum raised against VGVBV. Apart from the homologous antigen, the VGVBV
      antiserum reacted only with Plum poxvirus (PPV). The VGVBV reacted strongly with
      the antisera to Bean yellow mosaic virus (BYMV), Bean common mosaic virus (BCMV)
      and Amaranthus leaf mottle virus (AmLMV) but weakly with antisera to PPV and
      Cowpea aphid-borne mosaic virus (CABMV) (all members of the family Potyviridae,
      the genus Potyvirus) in at least one of the assays used (indirect ELISA, dot-blot
      immunoassay and Western blot analysis). The results of our host range,
      cytopathological and serological studies and the available literature indicate
      that a hitherto difficult to transmit VGVBV has only been reported from Nigeria.
      We consider VGVBV a candidate for a new potyvirus. This virus should be further
      investigated to collect sufficient data for a qualified proposal of VGVBV as a
      new potyvirus.

PMID- 15745050
TI  - High Th1-type cytokine serum levels in patients with infectious mononucleosis.
AB  - Most adults are asymptomatically infected with Epstein-Barr virus (EBV). Primary
      EBV infection is commonly associated with acute infectious mononucleosis (IM). T
      cell immune activation plays an important role in EBV-associated diseases. IM
      shows a mainly Th1-type profile, so Th1-type cytokines such as interleukin-2 (IL
      2), interferon-gamma (IFN-gamma), and lymphotoxin (LT) are moderately enhanced.
      We measured IL-2 and IFN-gamma in serum during acute phase of the disease and
      during convalescence. Sera were collected from 23 IM patients, 13 patients with
      similar clinical manifestations but without IM, and 10 healthy donors. The levels
      of IL-2, IFN-gamma and IL-12 were significantly higher in patients with acute IM
      than in healthy individuals. IL-2, IFN-gamma and IL-12 decreased during
      convalescence. These three cytokines may be useful as sensitive markers of IM
      during severe illness and its later phases.

PMID- 15745051
TI  - Cloning and sequencing of coat protein gene of an Indian Odontoglossum ringspot
      virus isolate.

PMID- 15745052
TI  - [Tooth abrasion in the historic populations of Broumov].
AB  - Aging is accompanied by a natural decrease of the hard dental tissues. Occlusal
      and incisal tooth abrasion occurs during the normal mastication. In the study,
      the collection of 717 adult and child skulls without mandibles, and 518 isolated
      adult and child mandibles from the "Broumov Ossuary" (13th-18th century)--the
      Czech Republic was examined for the study of tooth abrasion. In the skulls and
      mandibles of the adult individuals high prevalence of both tooth abrasion and its
      high degree was ascertained. The established pattern of dental abrasion suggests
      an abrasive composition of diet at the historical Broumov populations and
      concurrently indicates that tooth age-abrasion can be used for the age-at-death
      determination solely in the context with the given particular historic epoch.

PMID- 15745053
TI  - [Francisella tularensis infection, or how to outsmart the certain death].
AB  - Francisella tularensis is an intracellular bacterial pathogen and is the
      causative agent of tularemia. Human become infected when manipulating with
      infected animals (usually rodents) or via arthropod vectors. In spite of the high
      virulence of the microbe still very little is known about its overall interaction
      with host cells and virulence factors identified to date show properties
      different from other bacterial species.

PMID- 15745054
TI  - [Genotoxic risk of Goeckerman's therapy of psoriasis. Pilot study--children].
AB  - Goeckerman's therapy of psoriasis includes combined exposure to therapeutic tar
      and UV-B radiation. In a pilot study of (12 children) a level of genotoxic risk
      of the therapy was evaluated by chromosomal aberration of peripheral lymphocytes.
      Results of the pilot study suggest possible genotoxic risk of the therapy.

PMID- 15745055
TI  - [Use of sucrose permeability test (SaLM) for detection of lesions of upper
      gastrointestinal tract mucosa in upper dyspepsia patients--a pilot study].
AB  - INTRODUCTION: Endoscopy, a golden standard with its high diagnostic value, is an
      invasive and unpleasant method as far as patients are concerned. So far there has
      been no available non-invasive test in the Czech Republic capable of
      distinguishing between heavy (i.e. peptic ulcer) and light (i.e. portal
      gastropathy) lesions of upper gastrointestinal mucosa. AIMS: In this pilot study
      we decided to test our modification of sucrose permeability test (SaLM test) on
      upper dyspepsia patients in our conditions. We first needed to compare the
      results of intestinal permeability obtained from the studied test (containing
      sucrose, a so called SaLM test) with a formerly established intestinal
      permeability test (containing glucose, a so called LaMa test) to know, if the new
      test could replace the old one. Then we wanted to find normal values of sucrose
      permeability, find a relationship between sucrose permeability and endoscopically
      verified damage to upper gastrointestinal mucosa and calculate sensitivity and
      specificity of SaLM test using results of gastroduodenoscopy. After that we tried
      to suggest possible future benefits of the test for clinical praxis. MATERIALS
      AND METHODS: A group of 10 young healthy volunteers underwent both SaLM and LaMa
      tests, which were made methodically indentical to compare the tests as to the
      results of intestinal permeability. The probands ingested SaLM solution with the
      following composition: sucrose (25.0 g), lactulose (10.0 g), mannitol (2.0 g),
      xylose (2.0 g) and water (up to 100 ml). Urine was collected for five hours and
      the samples were analysed using gas chromatography. From the results normal value
      of sucrose permeability was calculated, too. After that, 28 patients with upper
      dyspepsia were included in the study. They were divided into two groups (a group
      of light lesions with 9 patients and a group of heavy lesions counting 19
      patients) according to gastroscopical findings. We compared the results among the
      three groups. RESULTS: In our volunteers, the intestinal permeability values
      using LaMa and SaLM tests showed normal distributions. No statistically
      significant difference (p < 0.05) was found between the tests in regard to the
      intestinal permeability. The normal value of sucrose permeability was found to be
      up to 0.10% of the amount taken orally. The permeability for sucrose was
      significantly higher (p < 0.01) in patients with heavy lesions (0.527 +/- 0.414)
      versus those with light ones (0.178 +/- 0.090). Moreover, the latter had their
      sucrose permeability values significantly higher than healthy volunteers (0.088
      +/- 0.067), (p < 0.05). Sensitivity and specificity of the test for heavy upper
      gastrointestinal mucosal damage was 0.95 and 0.33, respectively. CONCLUSION: SaLM
      test could replace LaMa test without having a significant effect on the
      intestinal permeability results. It is feasible to study SaLM test on bigger sets
      of patients and specify it in more detail, since the results of our pilot study
      (in accordance with many other studies) make it promising for various clinical
      applications (i.e. in upper dyspepsia patients it might help in deciding about
      urgency and reasonability of gastroduodenoscopy).

PMID- 15745056
TI  - [Congenital dyserythropoietic anemia--type II (CDA-II) in 3 siblings with long
      term follow up and iron overload].
AB  - The diagnosis of congenital dyserythropioetic anemia-type II (CDA-II) was
      established in 1974 in three siblings aged 20, 18 and 5 years, respectively.
      Liver biopsy performed in two elder siblings on admission revealed liver
      siderosis. Anemia showing haemolytic component with destruction of erythrocytes
      in the spleen was corrected after splenectomy. Increased number of erythrocytes
      showing "the double membrane phenomenon" was found in the peripheral blood after
      splenectomy. All three siblings developed cholecystolithiasis with
      choledocholithiasis and obstructive jaundice in two of them. Two patients at the
      age of 49 and 34 years (the third died in an accident at the age of 40 years)
      developed 29 years after the diagnosis of CDA-II had been established signs of
      iron overload with transferin saturation 99%, serum ferritin 1450.4 microg/l and
      1131.7 microg/l respectively, and hepatic iron concentration (dry weight) 14,843
      microg/g and 15,415 microg/g (norm 70-1400 microg/g) respectively. No mutations
      of HFE gene (C282Y and H63D) were found. Liver biopsy showed heavy accumulation
      of hemosiderin in hepatocytes and reticuloendothelial cells. The structure of the
      liver tissue was not changed, only mild fibrosis in portal area was present in
      the older patient. Because of iron overload therapy with phlebotomy once monthly
      (400 ml) has been started in both patients. In peripheral blood films excess of
      Pappenheimer bodies was found.

PMID- 15745057
TI  - [Diisocyanate exposure as a cause of occupational asthma].
AB  - The authors present a summary of current knowledge on asthma caused by
      diisocyanates in workers under occupational exposure and introduce basic
      characteristics of these chemicals widely used in industry. Although they
      represent one of the main causes of occupational bronchial asthma (AB) in
      developed industrial countries, the number of reported asthma caused by
      diisocyanates is still relatively low in the Czech Republic--it represents less
      than ten percent of all reported occupational asthma. One of the possible reasons
      is demanding diagnostics and assessment of occupational impact of chemical noxae
      with combined effect mechanism characteristic of low-molecular diisocyanates.
      Studies concerned with presented topics support the concept that AB caused by
      diisocyanates shows clinical features of both atopic and nonatopic asthma. AB
      caused by DI is presented by mixed type of the TH1/TH2 response, influx and
      regulatory role of CD4+ and CD8+ T lymphocytes. Mixed immunopathological
      mechanism and toxic effect are combined. For the present, evaluation of
      elimination and reexposure tests appear as the most valuable of available
      diagnostic methods, respectively simulated reexposure test in a health care
      facility and assesment of serum IgG or IgE antibodies against diisocyanates can
      be used. Data on occurrence of the disease in the Czech Republic and detailed
      information on the sample of patients with respiratory allergic disease caused by
      diisocyanates reported by the Clinic of Occupational Diseases of the Faculty
      Hospital in Hradec Kralove in 1994-2003 are presented. The disease was caused by
      evaporation of diisocyanates released during the production of polyurethanes and
      evaporation of adhesives containing toluendiisocyanate (TDI). In most cases,
      there were milder forms of asthma with significant improvement or elimination of
      difficulties occuring after occupational exposure was interrupted. Knowledge of
      the pathogenesis of AB caused by diisocyanates should accelerate the development
      of diagnostic tests and consequent treatment intervention, as early determination
      of diagnosis and interruption of occupational exposure are essential for
      following prognosis of disease.

PMID- 15745058
TI  - [Age-related macular degeneration--contemporary possibilities of treatment].
AB  - Age-related macular degeneration (AMD) is a complex multifactorial disease, that
      affects the central region of the retina. AMD is a leading cause of blindness
      among people over 50 years of age in the industrialized world. Two types of
      macular degeneration exist, the "dry" form and the "wet-neovascular" form.
      Neovascular AMD is responsible for 80-90% of cases of severe, irreversible
      central vision loss in patients over 65 years of age with AMD. The authors
      present contemporary possibilities of treatment of the patients with this
      disease.

PMID- 15745059
TI  - [Surgical treatment of pneumothorax].
AB  - Complex therapy of pneumothorax is a multidisciplinary task. The point is: the
      etiology of pneumothorax is different but the resulting risk for the patient is
      always the same. Therefore, there is necessity of cooperation of several medical
      branches in causal therapy. The authors present experience with pneumothorax
      therapy in Cardiosurgical Department in 5-year interval in 101 patients, where
      they carried out surgical as well as conservative therapy approaches.

PMID- 15745060
TI  - [Sir William Osler's legacy].
AB  - William Osler (1849-1919) is generally regarded as one of the greatest and most
      respected physicians in the history of medicine. As an outstanding clinician and
      a professor of medicine at four universities in three countries he exerted a
      profound influence on medical education. His textbook "The Principles and
      Practice of Medicine" became the most popular treatise on medicine in the world.
      He emphasized the value of hard work. His compassion and concern for patients,
      students and colleagues reflected his personality. Osler's humanism, his
      philosophy and views did not lose their validity even today.

PMID- 15745061
TI  - [Current advances in leprosy research activities].
AB  - Due to the advent of multi-drug therapy (MDT) recommended by the WHO, for the
      treatment of leprosy, presently, leprosy is regarded as a "curable disease". The
      number of new cases in Japan is relatively very low, due to which the disease is
      likely to be neglected, but on scientific grounds, there is a necessity to
      perform in depth studies. Leprosy caused by M. leprae is still unclear on various
      aspects including transmission, immunology, nerve damage etc. Here we introduce
      the recent advances in the field of basic leprosy research.

PMID- 15745062
TI  - [History of Hansen's disease control policy in the United States].
AB  - Federal government set up the institutions for the study and treatment of
      Hansen's disease patients in Hawaii in 1905. Then in 1917, a legislation was made
      to build a national leprosarium (leper home), authorize the Surgeon General (SG)
      to receive into that institution any person afflicted with leprosy who presents
      himself or herself for care, detention, and treatment, or any person afflicted
      with leprosy duly consigned to said home by the proper health authorities. The
      National Leprosarium (later renamed as National Hansen's Disease Center) opened
      in Carville in 1922. Although promin treatment had started in the early 1940s,
      the Public Health Service Act of 1944 retained the SG's authority for detention
      and apprehension. Discharge codes were gradually loosened since then, but the
      efforts to revise the Act were never successful for a long time. It was in 1985
      when the Act was abolished. Provision of long-term care for new patients at the
      Center was terminated finally in 1997.

PMID- 15745063
TI  - [In vitro and in vivo activities of newly synthesized fluoroquinolones WQ-3345
      and WQ-3402 against Mycobacterium leprae].
AB  - Activities of newly synthesized fluoroquinolnes WQ-3345 and WQ-3402 against M.
      leprae were measured by using the Buddemeyer method. The % inhibition of the
      examined drugs for M. leprae was in the order of RFP > WQ-3402 > SPFX > GFLX > WQ
      3345 > LVFX. The anti-M. leprae activity of WQ-3402 was found to be strongest in
      these five fluoroquinolones when examined by this method, and the activity of WQ
      3345 was weaker than that of GFLX. The anti-M. leprae activities of WQ-3345 and
      WQ-3402 were measured by a mouse footpad method using nude mice. The inhibitory
      effects on the growth of M. leprae inoculated into the footpads were found to be
      incomplete after orally administered with WQ-3345 or WQ-3402 respectively at
      dosages of 10 and 20 mg/kg, and the incomplete inhibition was again was again
      found even at a dosage of 30, 40, or 50 mg/kg im the latter.

PMID- 15745064
TI  - [Sexual orientation and self-esteem maintenance: a sense of social inclusion].
AB  - Self-esteem of sexual orientation minority members is not necessarily low,
      contrary to what might be theoretically expected. An explanation has been offered
      that self-protective strategies were in use. Instead, it is argued in this paper
      that sense of social inclusion plays an important role, and two questionnaire
      studies examined the possibility. In Study I, 214 members of sexual orientation
      minority completed a set of questionnaires. Results showed that sense of
      acceptance by others had a positive relationship with self-esteem, but use of
      self-protective strategies did not. In Study 2,218 who were not minority members
      completed the same set of questionnaires. It was shown in the comparison that the
      relationship between self-esteem and sense of social inclusion was stronger for
      minority members than non-members. Sense of social inclusion thus appeared to
      help members of sexual orientation minority keep self-esteem high.

PMID- 15745065
TI  - [Relationship between two aspects of self-oriented perfectionism and self
      evaluative depression: using coping styles of uncontrollable events as
      mediators].
AB  - Self-oriented perfectionism has two aspects: pursuing perfection simply as a goal
      (Personal Standard: PS) and not accepting imperfection (Concern for Mistake: CM,
      Doubting of Action: D). The former is said to enhance mental health, while the
      latter deteriorates it. The latter aspect may also have vulnerability to
      uncontrollable events. The present study used causal modeling to investigate the
      relation of these two aspects, self-evaluative depression (composed of Self
      Esteem and Depression: SED), and styles of coping with uncontrollable events. A
      questionnaire measuring these concepts was completed by 169 college students, and
      the following results were yielded: Of the two aspects of self-oriented
      perfectionism, PS lowered SED, while CM and D heightened SED. PS increased such
      coping styles that attempt to control uncontrollable events as "Face and Act",
      "Positive expectation" and "Rumination", whereas CM increased "Avoidance",
      "Negative expectation" and "Self-blame" copings, which represent vulnerability to
      uncontrollable events. Moreover, Self-blame coping increased SED. These results
      suggested that CM was related, via Self-blame, to negative evaluation of
      imperfect self.

PMID- 15745066
TI  - [Are the visually marked items encoded as a context?].
AB  - We examined the attentional constraints of the contextual cueing effect known to
      occur only for attended items. We focused on whether the items not only attended
      to but also inhibited afterwards yield the effect or not. We adopted a hybrid
      paradigm of visual marking and contextual cueing procedures. In the experiment,
      half the distractors preceded the others and a target for one second. The results
      showed the contextual cueing effect even with visually marked items. These
      results suggest that spatial configurations previously attended to and inhibited
      afterwards can be encoded as visual context.

PMID- 15745067
TI  - [Sample size determination given data of preliminary experiment for student's t
      test, ANOVA and Tukey's multiple comparison].
AB  - The purpose of this article is to calculate the probability that a null
      hypothesis is rejected using data of preliminary experiment, and to determine an
      appropriate sample size based on that probability. The procedure to calculate
      that probability is as follows: (a)generate parameters from the posterior
      distribution of parameters given data of preliminary experiment; (b) generate
      test statistics from the conditional distribution given those parameters; (c)
      count how many of the generated test statistics exceed a critical value. Once the
      probability of rejecting null hypothesis is estimated, researchers can decide
      sample size corresponding to the desirable probability. Examples of the procedure
      are provided and compared with the traditional methods in the case of Student's t
      test.

PMID- 15745068
TI  - [Text comprehension and individual differences in working memory: the different
      contributions of the storage and the retrieval processing].
AB  - The present study addressed the relationship between an individual difference in
      the reading span test (RST) and the performance in text comprehension with
      respect to storage and retrieval systems. In Experiment 1, an effect of the
      serial recall task on performance in text comprehension was compared between high
      and low RST score groups. In Experiment 2, an effect of the word fluency task on
      performance in text comprehension of two groups was investigated. The results of
      both experiments showed that the performance in text comprehension of the low RST
      score group was impaired when the serial recall task was the secondary task; in
      contrast, the performance of the high RST score group was influenced when the
      word fluency task was used. The results suggested that the high RST score group
      comprehended text not only by using a temporary storage system but also by using
      a retrieval system efficiently.

PMID- 15745069
TI  - [Temporal characteristics of signal enhancement by visual attention].
AB  - The effects of spatial attention by precuing the location of the target stimulus
      are attributed to two mechanisms: noise reduction and stimulus signal
      enhancement. The signal enhancement hypothesis proposes that attention directly
      improves the quality of the stimulus representation. In this study, we examined
      the temporal characteristics of signal enhancement by combining an orientation
      discrimination sensitivity measurement and the Speed-Accuracy Trade-off
      procedure. To minimize the spatial uncertainty, target position was indicated in
      advance. We found that the valid precue improved the orientation discrimination
      sensitivity by speeding up the rate of information processing, while not
      affecting the asymptotic level of sensitivity. We conclude that the signal
      enhancement by the attention is observed only at the early stage of information
      processing, and it has different temporal characteristics from that of noise
      reduction.

PMID- 15745070
TI  - [Psychological factors and effects of reaching settlements in civil actions].
AB  - The purpose of this research was to examine disputant's cognitive processes in a
      civil suit empirically. We analyzed the data which was gathered by The Judicial
      Reform Council. We assumed that a disputant who wishes to reduce costs for suit
      often chooses settlement procedure in the judicial process and who thinks highly
      of the judge is more likely to accept judge's proposition. Although we could not
      confirm the effect of cost anxiety, the results suggested that a good impression
      forward the judge promotes reaching settlement. It was also suggested that
      corporations are apt to compound more than natural persons. In addition, analysis
      of effect of settlement indicated that reaching settlement promotes acceptance,
      agreement and satisfaction about unfavorable outcomes.

PMID- 15745071
TI  - [Comparison with friends, closeness of friendship, and academic achievement and
      perceived academic competence of junior high school students].
AB  - The purpose of this study was to examine the influence friends had on academic
      competence of children. Junior high school students, 322 in total, participated
      in the study. Results essentially replicated previous studies on the relationship
      between academic achievement and perceived academic competence, and it was
      positive. The present study also found that when the friendship was close and
      reciprocal, the achievement-competence relationship was strong if the friend's
      achievement was low, and weak if it was high. In contrast, children's perception
      of academic competence was not influenced if the comparison of academic
      achievement was made with a friend who was not very close.

PMID- 15745072
TI  - [Development of a proactive and reactive aggression questionnaire for elementary
      school children].
AB  - The purpose of the present study was to develop a standardized questionnaire to
      measure proactive and reactive aggression in children. In Study 1, the
      questionnaire was administered to fourth- through sixth-grade children (n = 700)
      to investigate its factor structure and internal consistency. Moreover, in order
      to examine reproducibility, it was administered twice, at the interval of about
      three weeks, to 132 of these children. Statistical analyses of the data have
      yielded three factors: proactive-relational aggression, reactive-expressive
      aggression, and reactive-inexpressive aggression; and have confirmed that the
      questionnaire was reliable and internally consistent. In Study 2, 14 homeroom
      teachers of fourth- through sixth-grade nominated children who were most
      characteristic (n = 106) and least characteristic (n = 99) in each of the three
      factors. In addition, fifth- and sixth-grade children (n = 86) assessed their
      same-sex classmates according to the sentences that characterized each of the
      three factors. These children selected were also participants in Study 1. The
      results showed that the scale scores were consistent with the nominations and
      assessments, indicating the high construct validity of the questionnaire.

PMID- 15745073
TI  - [Effects of test format on learning strategy and perceived utility].
AB  - This study investigated effects of test format on use of different learning
      strategies and their perceived utility. It was conducted in a classroom setting.
      Sixty seven (67) eighth grade students participated in the study, and were
      randomly assigned to one of two experimental conditions: fill-in test or essay
      test conditions. They took a history class for five days, and at the end of each
      session, took a test about the lecture with the format of their conditions.
      Results showed that in comparison with fill-in format, essay format facilitated
      use of deep-processing learning strategy, and decreased use of such strategies as
      rote memory. No significant effect was found for perceived utility of learning
      strategies, suggesting that it did not mediate the format effect. Underlying
      mechanism of the format effect and practical value of the current research were
      discussed.

PMID- 15745074
TI  - [Basic study on wartime reminiscences of older adults in Okinawa].
AB  - This study investigated retrospectively the thoughts people had of World War II,
      especially the Battle of Okinawa at that time, and their current evaluation of
      their own wartime experience. A questionnaire survey was conducted, and 217 older
      adults, 114 women and 103 men between 65 and 88 years old, participated. Results
      indicated that men generally had more negative feelings than women at the end of
      the war. And psychological damages caused by traumatic war memories seemed to
      have persisted in not a few individuals in spite of over half a century since the
      end of the war. However, others had been more positive and accepting toward their
      wartime experiences. This difference appeared to be related to qualitative
      differences of various experiences, as well as the person's age. It is argued
      that a vigorous approach will be necessary for this sort of study of Japanese war
      victims from a number of viewpoints.

PMID- 15745076
TI  - Evaluation of mucosal eosinophils in the pediatric colon.
AB  - To evaluate the clinical significance of colonic eosinophilia, we conducted a
      retrospective study of all children older than 1 year evaluated at Children's
      Hospital of Pittsburgh from January 1999 to June 2001 with a description of
      colonic eosinophilia in the pathology report. Medical records were reviewed.
      Diagnoses were confirmed by contacting the patients. Histological slides (H&E)
      were reviewed by an investigator blind to the patients' data. Biopsies were
      grouped according to the site they were taken from and then screened at low power
      for areas of maximal eosinophilia for further quantitative analysis. Results of
      manual counts were validated by image analysis using Metaphor Image Analysis
      Software. Sixty-nine children with colonic eosinophilia were identified (36 male;
      mean age, 135.2 +/- 55.4 months). Their final diagnoses were inflammatory bowel
      disease in 32% (group A), irritable bowel syndrome in 33% (group B), food
      allergies in 10% (group C), and other diagnoses in 25% (group D). The maximal
      eosinophil count per crypt area was significantly (P < 0.05) higher in group A vs
      groups B, C, and D (34.8 +/- 17.1 vs 21.3 +/- 8.8, 25.4 +/- 16.7, and 24.2 +/-
      9.7, respectively). The total cellularity of the lamina propria was considered
      high only in group A (P < 0.05 vs groups B and C). A mostly equal vertical
      distribution of eosinophils throughout the lamina propria was found significantly
      more frequently in group A vs groups C (P = 0.04) and D (P = 0.007). We conclude
      that children with inflammatory bowel disease have an equal distribution of
      eosinophils throughout the lamina propria, with intraepithelial and intracryptal
      eosinophils and with a higher overall total cellularity. In irritable bowel
      syndrome and patients with a variety of other diagnoses, including allergies, the
      distribution is mostly superficial, with a lower total cellularity.

PMID- 15745075
TI  - Neutropenic enterocolitis in adults: case series and review of the literature.
AB  - Necrotizing enterocolitis in adults is a rare disease and, in the past, has been
      associated with nearly uniform mortality. In recent years, necrotizing
      enterocolitis, now termed neutropenic enterocolitis, in adults has become more
      prevalent as a complication of aggressive systemic chemotherapy. In this report,
      we discuss two cases of neutropenic enterocolitis secondary to the administration
      of systemic chemotherapy in adult cancer patients: one with lung carcinoma, the
      other with leukemia. Both patients were successfully treated with early surgical
      intervention for resection of all necrotizing enteric lesions, and subsequent
      aggressive critical care support. Our experience suggests that early surgical
      intervention in adult patients with intestinal necrosis due to chemotherapy is
      essential to avoid mortality from this condition. Given the widespread,
      aggressive use of systemic chemotherapy in the neoadjuvant setting, patients at
      risk for this potentially lethal complication of neutropenic enterocolitis are
      increasingly common.

PMID- 15745077
TI  - Occurrence of gastrointestinal opportunistic disorders in AIDS despite the use of
      highly active antiretroviral therapy.
AB  - Since the introduction of highly active antiretroviral therapy (HAART), the
      frequency of opportunistic disorders (ODs) of the gastrointestinal (GI) tract in
      human immunodeficiency virus (HIV)-infected patients has fallen dramatically. We
      have found, however, that despite the use of HAART, HIV-infected patients can
      still present with GI ODs. To evaluate the prevalence of GI ODs in HIV-infected
      patients on HAART who were undergoing endoscopic evaluation for GI-related
      symptoms. From January 1996 through February 2002, all HIV-infected patients
      undergoing GI endoscopy were prospectively identified; mucosal biopsies were
      obtained in a standardized fashion and histologic specimens were examined by a
      single GI pathologist. All the patients on HAART presenting with a GI OD are
      described. Results showed that 294 patients (88% men; mean age, 36.5 +/- 10
      years; median CD4 lymphocyte count, 64 cells/microl; range, 1-884; median viral
      RNA level, 40,357 copies/ml; range, 0-7,721,715) underwent 401 upper and/or lower
      endoscopies during the study period. The use of HAART increased from 10% in early
      1996 to 85% in 2002. Nevertheless we found that 27 patients (9%) presented with a
      GI OD despite HAART. Forty percent of the patients with a GI OD were noncompliant
      with HAART. We conclude that GI ODs can occur despite HAART and normal CD4
      counts. The prevalence of GI ODs in HIV-infected patients taking HAART is 9%. The
      reasons for this are multifactorial and likely include noncompliance with
      medications, viral resistance to the drugs, and decreased drug bioavailability.
      Although the use of HAART has led to a decreased incidence of GI ODs in AIDS, the
      gastroenterologist evaluating these patients should not discard the possibility
      that the GI symptoms in HIV-infected patients taking HAART may be secondary to an
      OD, even when the CD4 count is normal and the viral load is low.

PMID- 15745078
TI  - Risk factors for thromboembolic complications in inflammatory bowel disease: the
      role of hyperhomocysteinaemia.
AB  - Inflammatory bowel disease (IBD) is associated with an increased risk for
      thromboembolic events. Aim of this study was to examine the relationship of
      hyperhomocysteinemia and thrombosis in IBD patients and to assess the role of
      this factor in addition to other known prothrombotic abnormalities. IBD patients
      with a history of thrombosis (n = 22) and sex-, age-, and diagnosis-matched IBD
      controls (n = 23) were studied. Homocysteine (tHcy) was assessed before and after
      methionine loading. Plasma levels of protein C, protein S, antithrombin III, and
      fibrinogen and the presence of anticardiolipin and antiphospholipid antibodies
      were determined and genetic testing for factor V Leiden and the prothrombin gene
      mutation was performed. Results showed that fasting homocysteine levels in IBD
      patients with a history of arterial or venous thrombosis tended to be higher than
      in IBD controls, although not significantly. The increase in homocysteine levels
      after methionine loading was significantly higher in IBD patients in the arterial
      thrombosis group than in IBD controls (40.9 +/- 17.7 vs. 27.2 +/- 9.9 microM; P <
      0.05). Among the other prothrombotic factors, only factor V Leiden was
      significantly associated with a history of venous thrombosis (20 vs. 0%). At
      least one risk factor was found in 64% of the IBD patients with previous
      thromboembolic complications. We conclude that there is an association between
      hyperhomocysteinemia and a history of arterial thrombosis in IBD patients. We
      confirm the high prevalence of factor V Leiden in IBD patients with a history of
      venous thrombosis. In the majority of IBD patients with previous thromboembolic
      complications, at least one prothrombotic risk factor is detected.

PMID- 15745079
TI  - Effect of reducing sodium or glucose concentration in a hypo-osmolar ORS (oral
      rehydration salts) on absorption efficiency: marker perfusion study in rat
      jejunum.
AB  - We evaluated the relative absorption efficiency of reducing the sodium or glucose
      concentration to make an ORS hypo-osmolar in a perfusion model. In nine adult
      albino rats 30 cm of jejunum was perfused at 0.4 ml/min with three glucose salt
      solutions for 45 min each, one with 60 mM sodium, 111 mM glucose, and osmolarity
      247, one with 90 mM sodium, 60 mM glucose, and osmolarity 250, and one with 90 mM
      sodium, (111 mM) glucose, and osmolarity 301 (control solution). Each contained 2
      g/L polyethylene glycol 4000 as a marker. The net water and sodium absorption
      were 2.8 (P < 0.001) and 2.6 (P < 0.001) times higher from low-sodium and 1.7 (P
      < 0.001)- and 1.5 (P < 0.001)-fold higher from low-glucose solutions compared to
      the control. Net glucose absorption was 2.2 (P < 0.001)-fold higher from low
      sodium solutions compared to the control. The net water, sodium, potassium, and
      glucose absorptions were 1.6 (P < 0.001)-, 1.7 (P < 0.001)-, 1.36 (P < 0.05)-,
      and 4.15 (P < 0.001)-fold higher from low-sodium compared to low-glucose
      solutions. The hypo-osmolar ORS with reduced sodium was substantially more
      absorption efficient compared to the one with reduced glucose.

PMID- 15745080
TI  - Proposal of a new clinical index predictive of endoscopic severity in ulcerative
      colitis.
AB  - Assessment of disease activity by clinical parameters in ulcerative colitis is
      still controversial. Different clinical indexes have been proposed. Colonoscopy
      provides detailed information on mucosal damage. The aim of this study was to
      identify, among 21 clinical and laboratory parameters, which were predictive of
      endoscopic activity. We included 137 consecutive patients with ulcerative colitis
      who underwent colonoscopy, clinical examination, and blood tests within 4 weeks.
      Endoscopic severity was recorded using a simple score (range, 0-30). The multiple
      stepwise regression coefficient of each significant variable predictive of
      mucosal damage was used to develop a new activity index predictive of endoscopic
      appearance (Endoscopic-Clinical Correlation Index; ECCI). We tested the ability
      of our score to discriminate patients with severe endoscopic disease, calculating
      the area under the receiver operator characteristic curve, and we compared it to
      activity indexes proposed by other authors. Endoscopic severity was significantly
      influenced by four parameters: bloody stool, nocturnal bowel movements, body
      temperature >37.5 degrees C, and serum albumin. The new scoring system was
      calculated as ECCI = {[serum albumin x (-26)] + (bloody stool x 17) + (nocturnal
      bowel movements x 16) + [fever (0 or 1) x 39]} + 107. The ECCI accurately
      identified patients with severe endoscopic disease in our sample (sensitivity =
      81%, specificity = 95%). In conclusion, the ECCI should be useful in clinical
      practice because it is simple and strongly related to endoscopic activity.

PMID- 15745081
TI  - Validation of the treatment satisfaction questionnaire for Crohn's disease (TSQ
      C).
AB  - Treatment satisfaction is used to capture the full impact of disease on patients'
      lives. Currently, no instruments exist to evaluate satisfaction with
      pharmacologic therapy in patients with Crohn's disease (CD). The purpose of this
      study was to evaluate the psychometric properties of a treatment satisfaction
      questionnaire for CD (TSQ-C). The 36-item questionnaire was completed by CD
      patients who reported taking 5-aminosalicylic acid derivatives to treat their CD.
      Measures used in the validation study were the Inflammatory Bowel Disease
      Questionnaire (IBDQ), Crohn's Work Activity Impairment Index (CWAII), and patient
      reports of clinical indicators (e.g., number of active flares and medications
      taken). Exploratory factor analysis was used to evaluate the items and subscale
      structure. Internal consistency reliability and concurrent and discriminant
      validity were assessed using Cronbach's alpha, Pearson correlation coefficients,
      and analysis of variance. A total of 813 CD patients participated, with the
      majority being Caucasian (95.9%), female (67.0%), and >34 years old (86.1%).
      Patient-rated severity of CD was mild (49.3%), moderate (41.7%), and severe
      (7.5%). The final TSQ-C consisted of 32 items, with six subscales (Symptoms,
      Satisfaction, Expectations, Physician Relationships, Bother, and Cost), with each
      subscale score ranging from 1 to 6. Cronbach's alpha values ranged from 0.63
      (Cost) to 0.94 (Symptoms). Strong correlations were observed among the IBDQ,
      CWAII, and the Satisfaction and Symptoms subscales of the TSQ-C. TSQ-C subscales,
      particularly Symptoms and Satisfaction, significantly discriminated among levels
      of number of flares per year, patient-rated disease severity, and number of
      medication classes. The TSQ-C demonstrated excellent validity and reliability and
      appears to be a useful tool for evaluating satisfaction with pharmacologic
      therapy among patients with CD.

PMID- 15745082
TI  - Lactose hydrogen breath test in Giardia lamblia-positive patients.
AB  - The study was conducted in 54 adult patients with Giardia lamblia infection and
      54 adult controls to detect lactose maldigestion employing the noninvasive
      lactose hydrogen breath test. Forty of 54 (74%) patients with Giardia lamblia and
      24 of 54 (44.4%) controls showed lactose maldigestion (P < 0.01). In conclusion,
      this study shows that the frequency of lactose maldigestion is significantly
      higher in adult Indians suffering from Giardia lamblia infection compared to
      healthy individuals.

PMID- 15745083
TI  - Regression of inflammatory myofibroblastic tumor of the gastrointestinal tract
      under infliximab treatment.

PMID- 15745084
TI  - Gut permeability and intestinal mucins, invertase, and peroxidase in control and
      diabetes-prone BB rats fed either a protective or a diabetogenic diet.
AB  - This study deals with the enteropathy recently identified in diabetes-prone BB
      rats (BBdp). Diabetes-resistant BB rats (BBc) and BBdp rats were fed from days 32
      39 onward either a protective diabetes-retardant hydrolyzed casein diet (HC) or a
      plant-based diabetogenic (NTP) diet. The NTP diet decreased body weight and
      plasma insulin in BBc and BBdp rats. The BBdp rats displayed low intestinal
      invertase and increased intestinal peroxidase activity. In the BBdp rats fed the
      HC diet, the mucin content 30-35 cm below the pylorus was higher and the gut
      permeability lower than in the other three rat groups. There was a significant
      inverse correlation between gut permeability and the insulinogenic index in the
      BBdp rats fed the HC or NTP diet. Thus, in BBdp rats, the HC diet somehow
      prevents the increase in gut permeability and the decrease in the insulinogenic
      index otherwise found in some of these diabetes-prone animals.

PMID- 15745085
TI  - Do elevated plasma vasoactive intestinal polypeptide (VIP) levels cause small
      intestinal motor disturbances in humans?
AB  - Increased VIP plasma levels cause severe secretory diarrhea. Moreover, VIP is a
      major regulator of human intestinal motility. We hypothesized that VIP-mediated
      intestinal motility disturbances contribute to symptoms in elevated plasma VIP.
      Ten healthy volunteers were intubated twice with an orojejunal multilumen tube
      for duodenal manometry, jejunal perfusion of electrolyte and marker solution, and
      aspiration 10 and 40 cm more distally. All subjects randomly received intravenous
      infusion of saline and 300 pmol/kg x hr VIP for 5 hr. Results showed that VIP but
      not saline infusion induced netjejunal sodium secretion, watery diarrhea, and
      cardiovascular effects (P < 0.04). VIP did not alter intestinal motor activity or
      the mean duration of the interdigestive motility cycle or of phases I and II but
      nearly halved the duration of phase III (P = 0.0002). We conclude that increased
      plasma VIP markedly shortens human phase III activity without influencing other
      motility parameters. Hence, it is unlikely that VIP-mediated small intestinal
      motor disturbances cause symptoms in VIPOMA. Yet VIP may contribute to terminate
      phase III motility.

PMID- 15745086
TI  - Factors affecting the quantitative liver-spleen scan in normal individuals.
AB  - The quantitative liver-spleen scan (QLSS) can estimate the functional hepatic
      mass and the organ volumes by precise measurement of sulfur colloid (SC)
      distribution. The normal range determined in prior studies was estimated from
      patients with absence of chronic liver disease in which intense fasting appeared
      to produce slightly abnormal values. This study was to determine the effect of
      fasting or fed status and colloid particle size on quantitative measurements from
      the QLSS in a small cohort of normal individuals. Twelve persons without any
      medical problems had QLSS taken twice, 2 weeks apart, one fasting and one
      postprandial. Patients were scanned after injection of 5-6 mCi of SC; six
      patients were given solution A (5- to 12-microm particle size) and six patients
      solution B (2- to 12-microm particle size). SPECT and planar analysis were
      performed. SC distribution of total counts between the liver and the spleen
      {[L/(L + S)]t ratio}, liver-spleen index (LSI), and liver-bone marrow index (LBI)
      were calculated. The perfused hepatic mass (PHM) is the average of the LSI and
      LBI. Spleen and liver volumes are expressed as milliliters per pound ideal body
      weight (IBW). Results showed that the liver and spleen volumes (solution B
      postprandial, 9.27 +/- 2.48 and 1.47 +/- 0.57 ml/lb IBW, respectively) and LBI
      were not affected by the type of SC solution or by ingestion status. L/(L + S)
      total and pixel count ratios were significantly higher for solution B and
      postprandial studies. [L/(L + S)]t, LSI, and PHM increased significantly (P <
      0.05) from fasting to postprandial for solution A (0.71 +/- 0.13 vs 0.79 +/-
      0.08, 80 +/- 14 vs 91 +/- 8, and 102 +/- 10 vs 106 +/- 8, respectively) and for
      solution B (0.81 +/- 0.05 vs 0.90 +/- 0.02, 86 +/- 4 vs 95 +/- 3, and 101 +/- 5
      vs 110 +/- 3). Neither fasting nor postprandial LSI and PHM were significantly
      different between solution A and solution B. We conclude the following. (1) The
      QLSS functional indices in "true" normal patients fall within the previously
      reported normal range. (2) Calculated liver and spleen volumes are not altered by
      fasting or sulfur colloid particle size. (3) Fasting significantly decreased the
      [L/(L + S)]t, LSI, and PHM. (4) A postprandial scan may be preferable since the
      normal values for [L/(L + S)]t, LSI, and PHM are greater, with a narrower range,
      than fasting values.

PMID- 15745087
TI  - Development of hypoxemia in alcoholic liver disease.
AB  - The aim of this study was to investigate the arterial hypoxemia in Japanese
      patients with alcoholic liver disease (ALD) with regard to alcohol consumption
      and/or disease severity. Hypoxemia was observed in 78% patients with ALD and in
      all 46 patients with alcoholic liver cirrhosis (ALC) and 33 (56%) of 59 patients
      with noncirrhotic alcoholic liver disease (NCALD) (P < 0.0001). The partial
      pressure of oxygen (PaO2) was 71.1 +/- 5.2 mm Hg in ALC and 78.7 +/- 6.3 mm Hg in
      NCALD (P < 0.0001). The oxygen consumption in ALD was significantly higher than
      that in control subjects (P < 0.0001), and a high oxygen consumption was seen in
      88% of the patients with ALD, in all 46 ALC patients, and in 46 (78%) of 59 NCALD
      patients (P < 0.01). Following abstinence from alcohol, the PaO2 and oxygen
      consumption significantly recovered after day 2 (P < 0.0001), whereas the
      prothrombin index did not change in either NCALD or ALC patients. Multivariate
      analysis showed that alcohol consumption and oxygen consumption were significant
      independent predictors of PaO2. In conclusion, the present findings suggest that
      increased oxygen consumption due to alcohol ingestion is principally responsible
      for the hypoxemia in ALD patients.

PMID- 15745088
TI  - The hepatoprotective effect of hepatic stimulator substance (HSS) against liver
      regeneration arrest induced by acute ethanol intoxication.
AB  - Male Wistar rats were randomized to receive ethanol (2.5 ml/kg by gastric
      intubation every 8 hr; group I), equal volumes of isocaloric to ethanol sucrose
      solution (group II), or ethanol and HSS (100 mg/kg intraperitoneally 10 and 16 hr
      after partial hepatectomy; groups III and IV, respectively) for up to 96 hr after
      partial hepatectomy, with ethanol administration starting 1 hr prior to partial
      hepatectomy. Animals were killed at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48,
      60, and 96 hr after partial hepatectomy. The rate of liver regeneration was
      evaluated by the mitotic index in H&E-stained sections, immunochemical detection
      of Ki67 nuclear antigen, rate of [3H]thymidine incorporation into hepatic DNA,
      and liver thymidine kinase enzymatic activity. The biological activity of HSS in
      groups I and II rats was evaluated using a bioassay. Ethanol administration
      arrested liver regeneration during the first 32 hr after partial hepatectomy and
      suppressed HSS activity throughout the period examined. Liver regeneration
      progressed after 32 hr despite the low levels of HSS activity. HSS administration
      at 10 and 16 hr reversed liver regeneration arrest induced by ethanol. Acute
      ethanol administration induces cell cycle arrest during the first 32 hr after
      partial hepatectomy and suppression of HSS biological activity seems to
      contribute to this effect. HSS administration reversed the inhibitory effect of
      ethanol on liver regeneration and caused synchronized entrance of hepatocytes in
      the S phase of the cell cycle. HSS seems to participate in the network of growth
      factors controlling the G1/S cell cycle checkpoint.

PMID- 15745089
TI  - Asymptomatic advanced hepatocellular carcinoma presenting with spinal cord
      compression.
AB  - HCC is the most frequent primary malignancy of the liver and one of the most
      common cancers in the world. HCC is substantially a complication of liver
      cirrhosis, and because HBV and HCV are the predominant causes of chronic liver
      disease and cirrhosis worldwide, they have a propensity to lead to HCC. Common
      sites of HCC metastases include the lung, lymph nodes, and portal vein. Bony
      metastases are rare, and when they do occur the disease is usually far advanced
      and is associated with clinical manifestations of abdominal pain, weight loss,
      jaundice, hepato-splenomegaly, ascities, deranged LFTs, and elevated AFP. We
      report here a patient with asymptomatic advanced HCC, normal LFTs, and normal AFP
      values presenting with spinal cord compression.

PMID- 15745090
TI  - Fenofibrate-induced cirrhosis.

PMID- 15745091
TI  - Nodular regenerative hyperplasia of the liver and Castleman's disease: potential
      role of interleukin-6.

PMID- 15745092
TI  - Nonparasitic simple liver cyst: always a benign entity? Unusual presentation of a
      cystadenoma.

PMID- 15745093
TI  - Effects of orthotopic liver transplantation on the corrected QT interval in
      patients with end-stage liver disease.
AB  - Autonomic dysfunction is a recognized complication of end-stage liver disease
      (ESLD) associated with a poor prognosis. The corrected QT interval (QTc) on
      electrocardiogram is a marker of autonomic function. A few small studies have
      suggested that QTc may normalize with the return of liver function after
      orthotopic liver transplantation. We sought to determine how transplantation
      affects the QTc in patients with ESLD. The QTc from the pretransplantation
      evaluation of 46 patients with ESLD was compared with the QTc at 4-month
      posttransplantation follow-up. Other factors that can influence autonomic
      function also were evaluated. Most patients with ESLD (54%) showed a prolonged
      QTc (> or = 440 msec) at the pretransplantation evaluation (451 +/- 45 msec) that
      improved to within the normal range at posttransplantation follow-up (418 +/- 18
      msec; P < 0.001). There was no relationship between QTc prolongation and Child
      Turcotte-Pugh score, Model for End-Stage Liver Disease score, diabetes mellitus,
      age, or etiology of liver disease. Most patients with ESLD and a prolonged QTc
      will have a significant improvement in QTc after transplantation; however, 6.5%
      of patients in our study had a worsening of QTc after transplantation.

PMID- 15745094
TI  - Small-duct primary sclerosing cholangitis. A single-center seven-year experience.
AB  - Patients with cholestatic liver function tests and histological features of
      primary sclerosing cholangitis (PSC) but without the typical cholangiographic
      changes are considered to have small-duct PSC. The incidence of small-duct PSC
      and the natural history still is not known. We performed a retrospective search
      for patients diagnosed with small-duct PSC between January 1997 and December
      2003. The diagnosis of small-duct PSC was based on biochemical features of
      chronic cholestasis, liver biopsy findings consistent with PSC, and a normal
      cholangiogram on endoscopic retrograde cholangiography. Six patients fulfilled
      the diagnostic criteria for small-duct PSC. All patients received medical
      therapy. After a mean follow-up time of 26.0 +/- 29.8 months (range, 7-84
      months), all patients are alive. Repeated liver biopsy was performed in one
      patient, 58 months after the initial one, and disclosed amelioration of
      histological findings (reduction in the Ludwig fibrosis score from 4 to 2).
      During follow-up symptoms disappeared in all patients who were symptomatic at
      diagnosis; none of those who were asymptomatic at diagnosis developed symptoms.
      At the time of last follow-up all patients showed significant improvement of
      their biochemical variables compared to baseline. Administration of
      aminosalicylates seemed to be of benefit irrespective of the presence of
      inflammatory bowel disease. No patients underwent liver transplantation or
      developed cholangiocarcinoma. Even though our study included a low number of
      patients and the follow-up time was relatively short, we can suggest that small
      duct PSC rarely progresses to large-duct PSC and does not seem to be associated
      with development of cholangiocarcinoma. It thus seems to represent a separate
      entity with a favorable prognosis.

PMID- 15745095
TI  - Microsatellite analysis of sporadic flat and depressed lesions of the colon.
AB  - Prior studies of molecular and genetic derangements in flat and depressed lesions
      of the colon have revealed lower frequencies in a number of markers commonly
      present in exophytic lesions. These and other differences suggest that flat
      lesions are driven by alternative pathways. We reviewed a database of patients
      who had undergone endoscopic mucosal resection (EMR) for flat and depressed
      lesions at the University of Chicago from January 2001 to April 2003. Formalin
      fixed and paraffin-embedded colonic samples were retrieved from the tissue bank,
      and five standardized mononucleotide and dinucleotide microsatellite regions were
      analyzed for instability (MSI) using fluorescently labeled forward primers in
      nonmultiplex reactions. Sixteen patients were identified with flat or depressed
      lesions who had adequate tissue specimens available for MSI analysis. Of these
      specimens, eight were tubular adenomas, three were tubulovillous adenomas, and
      five were carcinomas in situ. Four of the lesions were microsatellite unstable,
      each at a single locus, and one lesion showed probable instability at a second
      locus. Eleven lesions were microsatellite stable. Aberrations in DNA repair
      mechanisms do not appear to significantly contribute to the molecular
      derangements underlying sporadic flat or depressed colonic lesions. The molecular
      bases that underlie the aggressive behavior of sporadic flat and depressed
      lesions remain to be determined, and further investigation is warranted.

PMID- 15745096
TI  - The effects of hepatic artery chemotherapy on viral hepatitis in patients with
      hepatocellular carcinoma.
AB  - Transcatheter arterial chemoembolization (TACE) or arterial Yttrium-90 (90Y)
      microspheres are used to treat unresectable hepatocellular carcinoma (HCC), but
      little is known about their effects on viral hepatitis. The aim of this study was
      to determine their effect on viral hepatitis in patients with HCC. We carried out
      a retrospective review of patients treated for HCC. Worsening of viral hepatitis
      was determined by serum chemistry and viral loads where available. Fifty-two
      patients treated with TACE were followed for a mean of 22.0 months. Thirty-nine
      patients (75%) had decreased/stable tumor. Two of the 39 (5%) patients with
      decreased/stable tumor burden had a sustained increase in bilirubin. None had a
      sustained ALT elevation or significant increase in viral load after TACE. Twenty
      four patients treated with 90Y microspheres were followed for a mean of 12.0
      months. Twenty-two of these had a decreased/stable tumor burden and no patient
      had a significant elevation of ALT. However, 7 of the 22 had a sustained
      bilirubin elevation. We conclude that neither TACE nor 90Y treatment was
      associated with worsening viral hepatitis in this group of HCC patients. The
      presence of chronic viral hepatitis with normal bilirubin should not exclude the
      use of these therapies in patients with unresectable HCC.

PMID- 15745097
TI  - Hereditary nonpolyposis colorectal cancer (Lynch syndrome): criteria for
      identification and management.
AB  - Hereditary nonpolyposis colorectal carcinoma (HNPCC), or Lynch syndrome, is an
      autosomal dominant syndrome accounting for 5 to 10% of the total colorectal
      cancer population. Patients with this syndrome develop colorectal carcinoma at an
      early age, but disease onset can happen in all age groups. Usually the carcinomas
      are synchronous or metachronous, and most of them arise proximal to the splenic
      flexure. The prognosis is better than for the sporadic form of cancer, and there
      is increased risk for cancer development in certain extracolonic sites, such as
      the endometrium, ovary, stomach, small bowel, hepatobiliary tract, ureter, and
      renal pelvis. Most patients with HNPCC have a mutation in one of two DNA mismatch
      repair genes, hMSH2 or hMLH 1. More than 90% of colorectal carcinoma patients
      with hMSH2 or hMLH1 demonstrate high-frequency microsatellite instability (MSI
      H). If a patient is suspected to belong to an HNPCC family, the first screening
      test should be immunohistochemistry for the detection of hMLH1 and hMSH2
      proteins, and if it is indicative, it should be followed by genomic sequencing
      for the identification of mutations in the mismatch repair genes. Genetic
      counseling and surveillance for high risk HNPCC family members should begin at
      age 25. Surveillance includes annual colonoscopy of the entire large bowel, with
      fecal occult blood testing performed twice a year. Systematic surveillance and
      individually designed treatment of affected patients may help to detect cancers
      at an earlier stage and subsequently improve the prognosis of the disease
      further.

PMID- 15745099
TI  - Computed tomographic presentation of mesenteric fibromatosis.

PMID- 15745098
TI  - Late-occurring liver metastases in colorectal cancer.

PMID- 15745100
TI  - A one-year follow-up study of endoluminal gastroplication (Endocinch) in GERD
      patients refractory to proton pump inhibitor therapy.
AB  - In a subset of patients with gastroesophageal reflux disease (GERD), symptoms
      persist in spite of proton pump inhibitor (PPI) therapy. Endoscopic
      gastroplication (EG) was reported to provide a novel therapeutic option in GERD.
      To evaluate symptomatic and objective outcome of EG in PPI refractory GERD,
      consecutive GERD patients with persisting reflux symptoms during at least 2
      months double dose PPI were recruited for EG (Endocinch). Exclusion criteria were
      high-grade esophagitis, Barrett's esophagus, and hiatal hernia > 3 cm. Symptoms
      and PPI use were evaluated before and 1, 3, and 12 months after the EG; 24-hr pH
      monitoring off PPI was performed before and after 3 and 12 months. All data are
      given as mean +/- SD and were analyzed by Student's t test. Twenty patients (10
      females; mean age, 45 +/- 11 years) were recruited. Under conscious sedation with
      midazolam (6 +/- 2 mg) and pethidine (53 +/- 5 mg), a mean of 2.0 +/- 0.2 sutures
      was applied during a procedure time of 33 +/- 6 min. Throat ache and mild
      epigastric pain for up to 3 days after the procedure were the only adverse
      events. At 3 and 12 months symptom score (11.6 +/- 6 vs. 6.4 +/- 3.7 [P < 0.01]
      and 7.1 +/- 4.5 [P < 0.05]) as well as pH monitoring (% time pH < 4: 17.0 +/-
      11.1 vs. 8.1 +/- 5.7% [P < 0.01] and 9.8 +/- 4.1% [P < 0.01]) significantly
      improved. Ph monitoring was normalized (< 4% of time) in seven patients after 3
      months. PPIs could be stopped in 13 patients, with 2 patients still using H2
      blockers and 1 using cisapride after 3 months. After 12 months only six patients
      were free of PPI use and pH monitoring was normalized in six patients. We
      conclude that EG provides short- and medium-term symptomatic and objective relief
      to a subset of GERD patients refractory to high-dose PPI.

PMID- 15745101
TI  - Restorative impact of rabeprazole on gastric mucus and mucin production
      impairment during naproxen administration: its potential clinical significance.
AB  - Rabeprazole augments gastric mucus and mucin production in humans. However, its
      potential restorative impact on gastric mucus and mucin production impairment,
      resulting from administration of naproxen, remained to be explored. Therefore, we
      measured the content of mucus and mucin in gastric juice (GJ) before and after
      administration of naproxen with rabeprazole or placebo. The study was approved by
      HSC at KUMC and conducted in 21 asymptomatic, H. pylori-negative volunteers in a
      double-blind, placebo-controlled, crossover design. The content of gastric mucus
      in GJ, after exhaustive dialysis and complete lyophilization, was assessed
      gravimetrically, whereas the content of mucin was measured after its purification
      with equilibrium density-gradient ultracentrifugation in CsC1. Gastric mucus
      secretion during administration of naproxen with placebo declined significantly
      both in basal (by 44%; P < 0.001) and in pentagastrin-stimulated (by 35%; P <
      0.001) conditions. Coadministration of rabeprazole significantly restored the
      naproxen-induced impairment in mucus production in basal conditions (by 47%; P <
      0.01) and by 22% during stimulation with pentagastrin. Gastric mucin secretion
      during naproxen/placebo administration also declined significantly in both basal
      (by 39%; P < 0.01) and stimulated (by 49%; P = 0.003) conditions. Rabeprazole
      also significantly restored the naproxen-induced decline of gastric mucin output
      during pentagastrin-stimulated conditions (by 67%; P = 0.003) and by 40% in basal
      conditions (P = 0.05). The restorative capacity of rabeprazole on the
      quantitative impairment of gastric mucus and mucin during administration of
      naproxen may translate into a clinical benefit of protection of the upper
      alimentary tract from NSAID-related mucosal injury.

PMID- 15745102
TI  - Effect of moxibustion at acupoints Ren-12 (Zhongwan), St-25 (Tianshu), and St-36
      (Zuzanli) in the prevention of gastric lesions induced by indomethacin in Wistar
      rats.
AB  - This study was aimed at assessing the physical characteristics underlying the
      action of moxibustion at acupoints Ren-12 (Zhongwan), St-25 (Tianshu), and St-36
      (Zuzanli) in preventing acute injuries of the gastric mucous membrane induced by
      indomethacin in Wistar rats. Induction of gastric lesions, by means of
      intragastric administration of indomethacin (100 mg/kg), in adult male Wistar
      rats was followed by treatment with moxibustion using Artemisia vulgaris dried
      leaves at 60 or 45 degrees C, heating with Artemisia vulgaris charcoal at 50
      degrees C, heating with a regular tobacco cigar at 50 degrees C, and heating with
      a regular water pad at 50 degrees C, The effects of the different heating
      protocols over the gastric lesions were then compared. In addition, another group
      of animals was pretreated with capsaicin (100 mg/kg, s.c.), in order to lesion C
      fibers and, 15 days later, subjected to indomethacin administration and
      moxibustion treatment. Moxibustion was significantly more efficient at 60 degrees
      C than at 45 degrees C in preventing gastric lesions triggered by indomethacin.
      Moxibustion applied in acupoints provided a significant reduction of the lesion
      area, which was two times less than that of animals stimulated in a nonacupoint
      (sham group). Comparing the therapeutic effects provided by different forms of
      heating over the gastric lesions, the burning of dry leaves of Artemisia vulgaris
      was significantly more efficient in preventing gastric lesions than moxibustion
      made with Artemisia charcoal or tobacco (cigar) or by heating the animal with a
      water pad. Desensitization of the afferent sensory C fibers by capsaicin
      significantly diminished the ability of moxibustion to block the lesions in the
      gastric mucous membrane. Moxibustion can efficiently prevent indomethacin-induced
      gastric lesions in rats and this effect is dependent on the temperature, the
      material used for moxibustion, the use of acupuncture points, and the integrity
      of C fibers.

PMID- 15745104
TI  - Regression of Helicobacter pylori-negative duodenal ulcers complicated by
      Schonlein-Henoch purpura with H. pylori eradication therapy: the first report.

PMID- 15745103
TI  - Genotypic and phenotypic stability of Helicobacter pylori markers in a nine-year
      follow-up study of patients with noneradicated infection.
AB  - The cagA gene, alleles of the vacA gene,random amplified polymorphic DNA (RAPD),
      and neutrophil activating capacity (HpNAC) were used to examine paired H. pylori
      isolates from 10 noneradicated individuals 9 years apart. Paired isolates from
      each patient were indistinguishable with regard to vacA alleles, RAPD, and HpNAC.
      Isolates from nine patients showed concordance for the cagA gene, which was not
      detected in the recent isolate of the tenth patient. Antibodies to CagA were,
      however, demonstrated in the serum specimens 9 years apart and were also present
      in two other patients whose paired isolates were cagA-, indicating the existence
      of both cagA+ and cagA-organisms, with the latter predominating in some patients.
      The present study suggests a greater stability of phenotypic and genotypic
      markers of H. pylori than previously regarded. This might be true for a community
      with low infection and transmission rates. Complementary techniques like
      microarrays might, however, disclose evolutionary changes not identified here.

PMID- 15745105
TI  - Is there anything to the reported association between Helicobacter pylori
      infection and autoimmune thyroiditis?
AB  - Higher serological prevalence rates of Helicobacter pylori (Hp) infection have
      been reported in patients with autoimmune thyroiditis (AT), and it has been
      suggested that monoclonal antibodies against Cag-A positive Hp strains can cross
      react with follicular cells of the thyroid gland. We studied the prevalence of AT
      and thyroid functional status in patients who underwent gastroscopy for dyspeptic
      symptoms. Patients were tested for TSH, free thyroid hormones, and
      antithyroglobulin and antithyroperoxidase antibodies (ATPO). Hp positivity was
      determined using urea breath test (UBT). Serum samples from 302 patients (59.9%
      women) were evaluated. One hundred ninety-one subjects (63.2%) were Hp-negative,
      and 111 of 302 (36.8%) were Hp-positive. Forty-three of 191 Hp-negative patients
      (22.5%; 95% CI, 17.1-29.0%) had an increase of either antibody, compared to 30 of
      111 (27.0%; 95% CI, 19.6-36.0%) Hp-positive patients (P = 0.40). Similar results
      were obtained using positivity for both antibodies (7.3 vs. 7.2%; P = 1) or for
      ATPO (18.8 vs. 21.6%; P = 0.54). The prevalences of hypothyroidism (4.7 vs. 5.5%)
      or hyperthyroidism (5.8 vs. 5.5%) were also similar (P = 0.95). Hormonal levels
      were not different in the two groups (P > 0.22 in all cases). The previously
      reported association between AT and Hp infection was not observed in our study.
      Infection by Hp does not appear to increase the risk of AT in individuals with
      dyspeptic symptoms, and screening for this condition in patients with a positive
      UBT is not indicated.

PMID- 15745106
TI  - Use of methylene blue for detection of specialized intestinal metaplasia in GERD
      patients presenting for screening upper endoscopy.
AB  - The ability of randomly obtained biopsy specimens to identify intestinal
      metaplasia in the distal esophagus is low. Use of vital staining has been
      suggested, as stains are taken up by areas histologically identified as
      specialized intestinal metaplasia (SIM). This study evaluated the role of
      methylene blue (MB) staining for identification of SIM in GERD patients
      undergoing a screening endoscopy. Chromoendoscopy of the distal esophagus using
      1% MB was performed on 52 GERD patients presenting for their first endoscopy.
      Biopsies were obtained from areas that were stained darkly, stained lightly,
      unstained, or macroscopically abnormal. In patients with no MB staining, four
      quadrant biopsy of the distal esophagus was performed. Twenty-seven patients
      (52%) showed staining with MB, while 25 patients did not. Two hundred sixty-six
      biopsies were obtained. SIM was detected in 11 (21%) subjects (SIM+) but not in
      the remaining 41 (SIM-). One hundred sixty-five biopsies were unstained (25 SIM+,
      140 SIM-) and 101 were stained (12 SIM+, 89 SIM-). The per-biopsy sensitivity and
      specificity of MB for detection of SIM were 32.4 and 85%, while the per-patient
      sensitivity and specificity were 63.3 and 51.2%. MB staining for detection of SIM
      in GERD patients without a macroscopic appearance suggestive of a columnar-lined
      esophagus is a poor screening tool for SIM.

PMID- 15745107
TI  - Use of the six-shooter ligation device in the management of bleeding esophageal
      varices: a developing-country experience.
AB  - Endoscopic variceal ligation has emerged as a superior alternative to endoscopic
      injection sclerotherapy, however, the "single-shot" mechanism of the generally
      used Stiegman-Goff ligator made the procedure tedious and time-consuming and
      required overtube placement, associated with discomfort and potentially life
      threatening complications. In this study we describe our experience with the
      Saeed Six-Shooter (multiple-ligation device). Fifty consecutive patients with
      variceal bleeding were prospectively studied. After initial endoscopic ligation,
      subsequent sessions were every 2 weeks. Study outcomes were: the ability to
      control active bleeding, the frequencies of rebleeding, the number of treatment
      sessions and time required for irradication, the percentage eradication of
      varices, complications, and mortality. Active bleeding was controlled in all
      eight (100%) patients. Four (8%) patients rebled, three from esophageal varices,
      and one from portal hypertensive gastropathy. Esophageal varices were eradicated
      in 47 (94%) patients (3.1 +/- 1.3 sessions). Time needed till eradication was 6.2
      +/- 1.9 weeks. Chest pain was reported in two (4%), low, grade pyrexia in two
      (4%), and pneumonia in one (2%) patient. There were three deaths, none due to
      exsanguination. The Six-Shooter is a safe and efficient device for the endoscopic
      ligation of esophageal varices which has overcome the limitations of the single
      shot ligator: (1) Visualization is better (the endoscopic "tunnel vision" and
      internal light reflection from the stainless-steel banding cylinder of the single
      shot device are avoided); and (2) the use of an overtube is no longer necessary
      and serious complications can be avoided.

PMID- 15745108
TI  - Combination endoscopic band ligation and sclerotherapy compared with endoscopic
      band ligation alone for the secondary prophylaxis of esophageal variceal
      hemorrhage: a meta-analysis.
AB  - Endoscopic band ligation (EBL) is the community-accepted standard therapy for the
      secondary prophylaxis of esophageal variceal hemorrhage. Recent data indicate
      that combination EBL and sclerotherapy may be a more effective therapy than EBL
      alone. Yet existing data are conflicting. We therefore performed a meta-analysis
      to compare the efficacy and safety of EBL and sclerotherapy versus EBL alone for
      the secondary prophylaxis of esophageal variceal hemorrhage. We performed a
      systematic review of two computerized databases (MEDLINE and EMBASE) along with
      manual-searching of published abstracts to identify relevant citations without
      language restrictions from 1990 to 2002. Eight studies met explicit inclusion
      criteria. We performed meta-analysis of these studies to pool the relative risk
      for the following outcomes: esophageal variceal rebleeding, death, number of
      endoscopic sessions to achieve variceal obliteration, and therapeutic
      complications. There were no significant differences between EBL and
      sclerotherapy versus EBL alone in the risk of esophageal variceal rebleeding (RR
      = 1.05; 95% CI = 0.67-1.64; P = 0.83), death (RR = 0.99; 95% CI = 0.68-1.44; P =
      0.96), or number of endoscopic sessions to variceal obliteration (RR = 0.23; 95%
      CI = 0.055-0.51; P = 0.11). However, the incidence of esophageal stricture
      formation was significantly higher in the EBL group than in the sclerotherapy
      group. There is no evidence that the addition of sclerotherapy to endoscopic band
      ligation changes clinically relevant outcomes (variceal rebleeding, death, time
      to variceal obliteration) in the secondary prophylaxis of esophageal variceal
      hemorrhage. Moreover, combination EBL and sclerotherapy had more esophageal
      stricture formation than EBL alone.

PMID- 15745109
TI  - A randomized controlled trial of beta-blockers versus endoscopic band ligation
      for primary prophylaxis: a large sample size is required to show a difference in
      bleeding rates.
AB  - Primary prophylaxis with nonselective beta-blockers in high-risk subjects has
      been shown to be effective in reducing both esophageal variceal bleeding and
      mortality. Recently it has been suggested that band ligation may be a better
      option for primary prophylaxis. We compared nonselective beta-blockers with band
      ligation in patients with large varices (F2, F3) and elevated hepatic venous
      wedge pressure gradient (HVWPG, > or = 12 mm Hg). All patients were prospectively
      followed for variceal bleeding, mortality, and treatment-related complications.
      Based on previous published studies, we estimated that 90 patients in each arm
      would be required to show a difference in bleeding rate. The study was
      prematurely terminated when we realized that our estimated sample size was
      inadequate to show a difference based on the observed bleeding rate. At the time
      of termination, 31 patients (Child A, 11; B, 14; C, 6), with a mean HVWPG of 19
      +/- 9.1 mm Hg, were randomized to either band ligation (group A; n = 16) or beta
      blockers (group B; n = 15). Baseline demographics of both groups were similar and
      the mean follow-up period was 27.4 +/- 12.9 months. During the follow-up, two
      patients in group A and one patient in group B had bleeding. Nine patients (29%;
      group A, six; group B, three; P = ns) died due to non-bleeding-related causes and
      five (16%) patients (group A, three; group B, two) underwent liver
      transplantation. Treatment-related complication were minimal in both groups.
      Despite the selection of high-risk patients, the observed bleeding rate was much
      lower than anticipated. Based on our observed bleeding rates, 424 patients would
      be required in each arm to show a difference between band ligation and beta
      blocker therapy.

PMID- 15745110
TI  - Hepatic portal and mesenteric vein gas as a late complication of percutaneous
      endoscopic gastrostomy tube placement in an elderly patient.

PMID- 15745111
TI  - Anti-cancer and antibacterial trioxacarcins with high anti-malaria activity from
      a marine Streptomycete and their absolute stereochemistry.
AB  - The ethyl acetate extract from the Streptomyces sp. isolate B8652 delivered the
      trioxacarcins A to approximately C (2a to approximately 2c) and additionally
      three new derivatives designated as trioxacarcins D to approximately F (2d to
      approximately 2f). All trioxacarcins showed high anti-bacterial and some of them
      high anti-tumor and anti-malaria activity. The structures of the new antibiotics
      were derived from mass, 1D and 2D NMR spectra and confirmed by comparison of the
      NMR data with those of known derivatives. The absolute configuration of the
      trioxacarcins is deduced from the X-ray analysis of gutingimycin (2g) and from
      the known stereochemistry of the L-trioxacarcinoses A and B.

PMID- 15745112
TI  - FR227244, a novel antifungal antibiotic from Myrothecium cinctum No. 002
      Taxonomy, fermentation, isolation and physico-chemical properties.
AB  - A novel antifungal antibiotic, FR227244, was isolated from the culture broth of a
      fungal strain No. 002. The strain was identified as Myrothecium cinctum from
      morphological and physiological characteristics. This compound was isolated from
      the culture broth by solvent extraction, HP-20 and YMC ODS gel column
      chromatographies, and n-hexane precipitation. FR227244 is a white powder which
      melts at 210 to approximately 211 degrees C and possesses the molecular formula
      C38H58O11. FR227244 is a novel triterpene glycoside with antifungal activity
      against Aspergillus fumigatus. The effects of FR227244 on the morphology of A.
      fumigatus were shown to be similar to those of FR901379 which is a known 1,3-beta
      glucan synthase inhibitor.

PMID- 15745113
TI  - FR227244, a novel antifungal antibiotic from Myrothecium cinctum No. 002. II.
      Biological properties and mode of action.
AB  - FR227244 is a novel triterpene glycoside that exhibits in vitro antifungal
      activity against filamentous fungi such as Aspergillus sp. and Trichophyton sp.
      and yeast such as Candida utilis and Candida parapsilosis but shows low activity
      against Candida albicans, Candida krusei and Candida tropicalis. Specifically,
      FR227244 exhibits in vitro and in vivo antifungal activity against Aspergillus
      fumigatus. The minimum effective concentration (MEC) of FR227244 against A.
      fumigatus FP1305 in a micro-broth dilution test was 0.031 microg/ml. FR227244
      showed good efficacy by subcutaneous injection and oral administration against A.
      fumigatus in a murine systemic infection model, with ED(50)s of 1.9 and 18 mg/kg,
      respectively. FR227244 inhibited glucan synthesis in a 1,3-beta-glucan synthase
      assay weakly and in whole cells strongly, but did not effect other macromolecule
      synthesis, including protein, nucleic acids, mannan and chitin. These results and
      the effect on hyphal morphology of A. fumigatus suggested that FR227244 showed
      antifungal activity based on inhibition of glucan synthesis.

PMID- 15745114
TI  - Transvalencin A, a thiazolidine zinc complex antibiotic produced by a clinical
      isolate of Nocardia transvalensis. I. Taxonomy, fermentation, isolation and
      biological activities.
AB  - A new thiazolidine-type antibiotic with zinc in its structure, designated
      transvalencin A, was isolated from Nocardia sp. IFM 10065, a clinical isolate
      from a patient with actinomycotic mycetoma. The strain was identified as Nocardia
      transvalensis based on its morphological, phenotypic and phylogenetic
      characteristics. Transvalencin A showed antimicrobial activity against fungi such
      as Trichophyton mentagrophytes and Cryptococcus neoformans. The antibiotic is
      also active against Gram-positive bacteria such as Micrococcus luteus. We
      observed higher activity for fungi in an acidic medium than in a neutral medium.

PMID- 15745115
TI  - Transvalencin A, a thiazolidine zinc complex antibiotic produced by a clinical
      isolate of Nocardia transvalensis. II. Structure elucidation.
AB  - A novel antifungal antibiotic, transvalencin A, is produced by Nocardia
      transvalensis IFM 10065 isolated from a patient with actinomycotic mycetoma in
      Japan. The antibiotic structure was elucidated using NMR, mass spectrometric
      investigations, and X-ray crystallographic analysis. Transvalencin A is a 1:1
      complex of a zinc and an organic acid with a phenolic substituent. Transvalencin
      A is comprised of o-substituted p-chlorophenol, tetrasubstituted oxazoline,
      disubstituted thiazolyl-N-methylthiazolidine and monosubstituted N
      methylthiazolidine.

PMID- 15745116
TI  - CRM-51006, a new phospholipase C (PLC) inhibitor, produced by unidentified fungal
      strain MT51005.

PMID- 15745117
TI  - YM-92447 (spinosulfate A), a neuraminidase inhibitor produced by an unidentified
      pycnidial fungus.

PMID- 15745118
TI  - A new screening method for pathway-specific antifungal compounds.

PMID- 15745119
TI  - Hybrid biosynthesis by targeted inactivation of polyketide synthases in the
      mycinamicin producer, Micromonospora griseorubida.

PMID- 15745120
TI  - Fredericamycin B and C from Streptomyces griseus: structure elucidation after 23
      years.

PMID- 15745121
TI  - The stereochemistry of micrococcin P1 reinvestigated.

PMID- 15745122
TI  - The many faces of bipolar disorder. How to tell them apart.
AB  - Bipolar disorder is a chronic disease characterized by depressive, manic or
      hypomanic, and mixed episodes. Bipolar disorder may be confused with unipolar
      depression, because patients with bipolar disorder are usually symptomatic with
      depression rather than mania. Bipolar disorder may also be misdiagnosed as
      schizophrenia, since both disorders can present with psychotic symptoms. For
      children, the principal differential diagnostic consideration is ADHD. Making the
      correct diagnosis has important prognostic and treatment implications.
      Comorbidities with personality disorders, substance and alcohol abuse or
      dependence, and anxiety disorders complicate assessment, treatment, and recovery.
      Effective pharmacotherapy and maintenance monitoring are critical in order to
      minimize the risk of relapse and associated disability, morbidity, and mortality.

PMID- 15745123
TI  - Latest therapies for bipolar disorder. Looking beyond lithium.
AB  - Effective treatments of bipolar disorder now extend to a panoply of choices that
      include various anticonvulsants and antipsychotics. Although lithium still has an
      important role, particularly in "classic" mania and suicide prevention, the other
      FDA-approved agents are better tolerated and more efficacious for mixed states
      and rapid cycling. It is not uncommon to use combination therapy for this
      challenging disorder. The FDA has approved olanzapine, risperidone, and
      quetiapine in combination with either lithium or divalproex for acute mania and
      the combination medication of olanzapine and fluoxetine for acute bipolar
      depression. Maintenance treatments that have received FDA approval include
      olanzapine and lamotrigine. Off-label use of adjunctive medications may be
      required to target residual symptoms.

PMID- 15745124
TI  - Ear, nose, and throat manifestations of gastroesophageal reflux disease.
      Complaints can be telltale signs.
AB  - GERD is one of the most common gastrointestinal conditions in the general US
      population. ENT become more commonly recognized or suspected by physicians,
      although the direct association between symptoms and acid reflux has been
      difficult to establish. Most patients with suspected supraesophageal GERD do not
      have the typical symptoms of heartburn and acid regurgitation. Possible
      mechanisms of GERD-mediated damage to extraesophageal structures include direct
      contact damage of mucosal surfaces by acid-pepsin exposure and a vagal reflex arc
      between the esophagus and the upper aerodigestive tract, triggered by acid
      reflux. Dual-channel ambulatory pH monitoring is the most sensitive and specific
      diagnostic test for determining transient reflux episodes, although demonstrating
      the presence of acid reflux alone does not prove that it is the cause of
      suspected GERD-related signs or symptoms. Therefore, physicians must sometimes
      resort to an empirical treatment strategy for both diagnosis and treatment. High
      dose PPI therapy for 9 to 12 weeks is the recognized first-line therapy;
      operative therapy is reserved for patients who have severe complications or whose
      condition incompletely responds to treatment. Complete lack of response should
      prompt reconsideration of alternative diagnoses. Controlled, well-designed
      clinical trials to assess treatment and more sophisticated techniques to quantify
      acid reflux are needed to help determine which patients with suspected
      extraesophageal complications actually have GERD as the primary cause.

PMID- 15745125
TI  - Patient notes: Understanding body mass index.

PMID- 15745126
TI  - Extracorporeal Life Support Registry Report 2004.
AB  - In this article, data from the annual international Extracorporeal Life Support
      Organization (ELSO) Registry Reports through July 2004 are presented. Nearly
      29,000 patients have received extracorporeal life support (ECLS). Of the
      patients, 66% (more than 19,000) were neonatal respiratory failure, with a 77%
      overall survival to discharge or transfer. The number of neonatal respiratory
      cases reported to the Registry has decreased from a peak of 1,500 patients in
      1992 and has leveled off at approximately 800 cases per year. The number of
      pediatric respiratory cases has remained at approximately 200 cases per year
      since 1993, with a 56% survival to discharge or transfer. Adult respiratory
      failure continues to be the smallest age group treated with extracorporeal
      membrane oxygenation (ECMO), with less than 100 cases per year. Survival to
      discharge, however, is comparable with pediatric respiratory failure (53%).
      Support continues to increase for cardiac failure across all age groups, with
      survival to discharge rates of 38%, 43%, and 33% for neonatal, pediatric, and
      adults, respectively. Survival in pediatric and adult respiratory failure cases
      supported with ECLS has remained fairly consistent over the past 5 years.

PMID- 15745127
TI  - Statistical correlation between transient pressure drop and cavitation at closure
      of a mechanical heart valve.
AB  - Cavitation on a mechanical heart valve (MHV) is attributable to transient
      regional pressure drop at the instant of valve closure. As a cavitation bubble
      collapses, it emits shock waves, which have the characteristics of high frequency
      oscillations (HFO) on a pressure time trace. The potential for such HFO bursts to
      cause material damage on an MHV can be measured by the cavitation impulse I,
      which is defined as the area under the trace of the HFO bursts. In the present
      study, experiments were conducted on a bileaflet MHV in a durability tester,
      operated at pulse rates from 300-1,000 bpm. In each case, the transient pressure
      near an occluder was monitored for 60,000 beats via a transducer. The peak
      pressure drop Pm and the corresponding cavitation impulse I obtained for the
      60,000 beat sequence are found to resemble sample records of two stationary
      stochastic processes, each of which follows a log normal distribution. Their
      first order probability density functions are estimated from the records. The
      correlation is investigated between I and Pm associated with each beat, which is
      found to be of statistical significance.

PMID- 15745128
TI  - Optimal mitral annular and subvalvular shape change created by the Coapsys device
      to treat functional mitral regurgitation.
AB  - We have reported that the Myocor Coapsys (Myocor, Inc, Maple Grove, MN) device
      treated functional mitral regurgitation (MR) by reducing mitral annular dimension
      and repositioning papillary muscles. This study was conducted to evaluate the
      optimal Coapsys device sizing level. The Coapsys device was implanted in seven
      dogs after induction of MR by rapid ventricular pacing. The device consists of
      anterior and posterior pads connected by a subvalvular cord. The device was
      tightened in 5% increments of the left ventricular epicardial to epicardial
      dimension up to 40%. Hemodynamic and echocardiographic measurements were repeated
      at each tightening level. The Coapsys significantly reduced or eliminated
      functional MR, and the reduction was maximized at the 30% tightening level or
      lower in all cases. Although the left ventricular end diastolic volume decreased
      significantly, forward stroke volume was maintained until the 35% tightening
      level. The forward ejection fraction significantly increased from 33 +/- 24% at
      baseline to 62 +/- 42% at 40% tightening level. Mean aortic pressure decreased
      slightly but significantly. The Coapsys device can be applied over a broad range
      of tightening levels with significant reduction in MR without negative
      physiologic impact. This feature makes the device usable [corrected] in a variety
      of clinical settings.

PMID- 15745129
TI  - Validation of mean arterial pressure as an indicator of acute changes in cardiac
      output.
AB  - Changes in mean arterial pressure (MAP) are often assumed to reflect changes in
      cardiac output (CO). A linear relationship is postulated to exist between these
      two quantities based upon the circuit model for systemic circulation. Previous
      studies have correlated changes in CO and MAP. However, to our knowledge, no
      studies have tested the relationship between CO and MAP in vivo without changes
      in systemic vascular resistance. Research on baroreceptor stimulation and
      vasomotor response has shown that vasomotor tone changes 15 to 60 seconds after
      an acute change in CO. Maximal activation of vasomotor response occurs after
      approximately 30 seconds. Thus MAP should correlate directly with CO during acute
      changes (< 15 seconds). To test this, we examined the relationship between CO and
      MAP during 10 second occlusions of the inferior vena cava in anesthetized pigs. A
      linear relationship existed between CO and MAP in seven pigs (%MAP = 0.60[%CO] -
      0.41, p = 0.0001). This study validates the use of MAP as an indicator of acute
      changes in CO. Fluctuations in MAP correlate well with acute changes in CO in the
      absence of changes in vascular tone.

PMID- 15745130
TI  - Comparison of pulsatile with nonpulsatile mechanical support in a porcine model
      of profound cardiogenic shock.
AB  - The aim of this study was to examine whether pulsatility by intraaortic balloon
      counterpulsation (IABP) is an important adjunct to the treatment of profound
      cardiogenic shock (CS) with a widely used, nonpulsatile centrifugal pump (CP). In
      each of 18 anesthetized, open chest pigs, the outflow cannula of the CP was
      inserted in the aortic arch through the right external carotid artery, and the
      inflow cannula of the CP was placed in the left atrium. A 40 cc IABP was
      subsequently placed in the descending aorta through the left external carotid
      artery. CS was induced by occlusion of coronary arteries and the infusion of
      propranolol and crystalloid fluid. Mean aortic pressure, pulse pressure, aortic
      end diastolic pressure, left ventricular end diastolic pressure, right atrial
      pressure, and heart rate were monitored. Cardiac output and left anterior
      descending artery flow were measured with a transit time ultrasound flowmeter.
      During profound CS, life sustaining hemodynamics were maintained only with the
      support of the assist devices. Hemodynamic support with the CP was associated
      with a nearly nonpulsatile flow and a pulse pressure of 7 +/- 4 mm Hg, which
      increased to 33 +/- 10 mm Hg (p = 0.000) after combining the CP with the IABP.
      Compared with the hemodynamic support offered by the CP alone, addition of the
      IABP increased mean aortic pressure from 40 +/- 15 to 50 +/- 16 mm Hg (p =
      0.000), cardiac output from 810 +/- 194 to 1,200 +/- 234 ml/min (p = 0.003), and
      left anterior descending artery flow from 26 +/- 10 to 39 +/- 14 ml/min (p =
      0.001). In profound CS, mechanical support provided by a continuous flow CP is
      enhanced by the added pulsatility of the IABP.

PMID- 15745131
TI  - The effects of pulsatile flow upon renal tissue perfusion during cardiopulmonary
      bypass: a comparative study of pulsatile and nonpulsatile flow.
AB  - This study was conducted to directly compare the effects of pulsatile and
      nonpulsatile blood flow in the extracorporeal circulation upon renal tissue
      perfusion by using a tissue perfusion measurement system. A total cardiopulmonary
      bypass circuit was constructed to accommodate twelve Yorkshire swine, weighing 20
      approximately 30 kg. Animals were randomly assigned to group 1 (n = 6,
      nonpulsatile centrifugal pump) or group 2 (n = 6, pulsatile T-PLS pump). A tissue
      perfusion measurement probe (Q-Flow 500) was inserted into the renal parenchymal
      tissue, and the extracorporeal circulation was maintained for an hour at a pump
      flow rate of 2 L/min after aortic cross-clamping. Tissue perfusion flow in the
      kidney was measured before bypass and every 10 minutes after bypass. Renal tissue
      perfusion flow was substantially higher in the pulsatile group throughout bypass
      (ranging 48.5-64.1 ml/min/100 g in group 1 vs. 51.0-88.1 ml/min/100 g in group
      2). The intergroup difference was significant at 30 minutes (47.5 +/- 18.3
      ml/min/100 g in group 1 vs. 83.4 +/- 28.5 ml/min/100 g in group 2; p = 0.026).
      Pulsatile flow achieves higher levels of tissue perfusion of the kidney during
      short-term extracorporeal circulation. A further study is required to observe the
      effects of pulsatile flow upon other vital organs and its long-term significance.

PMID- 15745132
TI  - Validation study of PulseCO system for continuous cardiac output measurement.
AB  - Ultrasonic flow probes have been used to optimize biventricular pacing
      immediately after cardiopulmonary bypass, improving cardiac output (CO) by 10%;
      however, flow probes must be removed with chest closure. The PulseCO system
      (LiDCO Limited, Cambridge, UK) may extend optimization into the postoperative
      period, but controlled validations have not been reported. Six anesthetized pigs
      were instrumented for right heart bypass. Flow was varied from 3 to 1 L/min and
      then back to 3 in 0.5 L/min increments for 60 second intervals. CO was measured
      by ultrasonic flow probe on the aorta and by PulseCO using a femoral arterial
      line. PulseCO and flow probe accurately measured CO (PulseCO R2: 0.79-0.95; flow
      probe R2: 0.96-0.99). At flow of 2 L/min, when the heart was paced 30 bpm over
      the sinus rate, PulseCO falsely indicated an increase in CO (2.13 vs. 2.30 L/min,
      p = 0.014). When mean arterial pressure was increased by 20% using a
      phenylephrine infusion, PulseCO falsely indicated an increase in CO (2.13 vs.
      2.47 L/min, p = 0.014). When mean arterial pressure was decreased by 20% using a
      nitroprusside infusion, PulseCO falsely indicated a decrease in CO (2.13 vs. 1.79
      L/min, p = 0.003). PulseCO appears to be useful for assessing acute changes in CO
      if its limitations are recognized.

PMID- 15745133
TI  - Effect of pump flow mode of novel left ventricular assist device upon end organ
      perfusion in dogs with doxorubicin induced heart failure.
AB  - End organ effects of nonpulsatile (NP) and pulsatile (P) left ventricular assist
      device (LVAD) flow were compared in a canine model of doxorubicin-induced heart
      failure. After heart failure induction, a prototype bimodal LVAD was implanted.
      Hemodynamics, cardiac dimensions, and myocardial metabolism were monitored with
      the LVAD off (baseline) and on (in NP and P modes at 70% or 100% power). End
      organ perfusion was assessed by colored microsphere analysis. Seven dogs were
      used: two died before pump implantation and were excluded from analysis, and the
      remaining five survived to study termination. At 70% NP, ascending aortic flow
      and myocardial oxygen consumption (MVO2) decreased significantly. At 100% NP, LV
      dimensions decreased, aortic systolic, pulse, and LV pressures decreased but not
      significantly, and ascending aorta flow reversed. At 100% NP, coronary blood
      flow, MVO2, and LV free wall subepicardial and subendocardial blood flows
      decreased significantly. However, as NP support increased, the
      subepicardial/subendocardial blood flow ratio remained near baseline. At 100% NP,
      right ventricular perfusion decreased but not significantly, cerebral perfusion
      decreased significantly, and renal perfusion stayed constant. P mode results were
      similar, except that ascending aorta flow decreased significantly at 100% P
      instead of reversing as at 100% NP. These results suggest that end organ
      perfusion is not differentially affected by LVAD flow mode during chronic heart
      failure.

PMID- 15745134
TI  - Novel maglev pump with a combined magnetic bearing.
AB  - The newly developed pump is a magnetically levitated centrifugal blood pump in
      which active and passive magnetic bearings are integrated to construct a durable
      ventricular assist device. The developed maglev centrifugal pump consists of an
      active magnetic bearing, a passive magnetic bearing, a levitated impeller, and a
      motor stator. The impeller is set between the active magnetic bearing and the
      motor stator. The active magnetic bearing uses four electromagnets to control the
      tilt and the axial position of the impeller. The radial movement of the levitated
      impeller is restricted with the passive stability dependent upon the top stator
      and the passive permanent magnetic bearing to reduce the energy consumption and
      the control system complexity. The top stator was designed based upon a magnetic
      field analysis to develop the maglev pump with sufficient passive stability in
      the radial direction. By implementing this analysis design, the oscillating
      amplitude of the impeller in the radial direction was cut in half when compared
      with the simple shape stator. This study concluded that the newly developed
      maglev centrifugal pump displayed excellent levitation performance and sufficient
      pump performance as a ventricular assist device.

PMID- 15745135
TI  - Precise quantification of pressure flow waveforms of a pulsatile ventricular
      assist device.
AB  - Unreliable quantification of flow pulsatility has hampered many efforts to assess
      the importance of pulsatile perfusion. Generation of pulsatile flow depends upon
      an energy gradient. It is necessary to quantify pressure flow waveforms in terms
      of hemodynamic energy levels to make a valid comparison between perfusion modes
      during chronic support. The objective of this study was to quantify pressure flow
      waveforms in terms of energy equivalent pressure (EEP) and surplus hemodynamic
      energy (SHE) levels in an adult mock loop using a pulsatile ventricle assist
      system (VAD). A 70 cc Pierce-Donachy pneumatic pulsatile VAD was used with a Penn
      State adult mock loop. The pump flow rate was kept constant at 5 L/min with pump
      rates of 70 and 80 bpm and mean aortic pressures (MAP) of 80, 90, and 100 mm Hg,
      respectively. Pump flows were adjusted by varying the systolic pressure, systolic
      duration, and the diastolic vacuum of the pneumatic drive unit. The aortic
      pressure was adjusted by varying the systemic resistance of the mock loop EEP (mm
      Hg) = (integral of fpdf)/(integral of fdt) SHE (ergs/cm3) = 1,332 [((integral of
      fpdt)/(integral of fdt))--MAP] were calculated at each experimental stage. The
      difference between the EEP and the MAP is the extra energy generated by this
      device. This difference is approximately 10% in a normal human heart. The EEP
      levels were 88.3 +/- 0.9 mm Hg, 98.1 +/- 1.3 mm Hg, and 107.4 +/- 1.0 mm Hg with
      a pump rate of 70 bpm and an aortic pressure of 80 mm Hg, 90 mm Hg, and 100 mm
      Hg, respectively. Surplus hemodynamic energy in terms of ergs/cm3 was 11,039 +/-
      1,236 ergs/cm3, 10,839 +/- 1,659 ergs/cm3, and 9,857 +/- 1,289 ergs/cm3,
      respectively. The percentage change from the mean aortic pressure to EEP was 10.4
      +/- 1.2%, 9.0 +/- 1.4%, and 7.4 +/- 1.0% at the same experimental stages. Similar
      results were obtained when the pump rate was changed from 70 bpm to 80 bpm. The
      EEP and SHE formulas are adequate to quantify different levels of pulsatility for
      direct and meaningful comparisons. This particular pulsatile VAD system produces
      near physiologic hemodynamic energy levels at each experimental stage.

PMID- 15745136
TI  - Magnetically suspended centrifugal blood pump with a radial magnetic driver.
AB  - A new magnetic bearing has been designed to achieve a low electronic power
      requirement and high stiffness. The magnetic bearing consists of 1) radial
      passive forces between the permanent magnet ring mounted inside the impeller
      rotor and the electromagnet core materials in the pump casing and 2) radial
      active forces generated by the electromagnets using the two gap sensor signals.
      The magnetic bearing was assembled into a centrifugal rotary blood pump (CRBP)
      driven with a radial, magnetic coupled driver. The impeller vane shape was
      designed based upon the computational fluid dynamic simulation. The diameter and
      height of the CRBP were 75 mm and 50 mm, respectively. The magnetic bearing
      system required the power of 1.0-1.4 W. The radial impeller movement was
      controlled to within +/- 10 microm. High stiffness in the noncontrolled axes, Z,
      phi, and theta, was obtained by the passive magnetic forces. The pump flow of 5
      L/min against 100 mm Hg head pressure was obtained at 1,800 rpm with the
      electrical to hydraulic efficiency being greater than 15%. The Normalized Index
      of Hemolysis (NIH) of the magnetic bearing CRBP was one fifth of the BioPump BP
      80 and one half of the NIKKISO HPM-15 after 4 hours. The newly designed magnetic
      bearing with two degrees of freedom control in combination with optimized
      impeller vane was successful in achieving an excellent hemolytic performance in
      comparison with the clinical centrifugal blood pumps.

PMID- 15745137
TI  - Tandem dialyzers with two monitors to meet target KT/V.
AB  - This preliminary trial was conducted to verify the impact upon delivered KT/V,
      the percentage change in the urea reduction ratio (%URR), and the frequency of
      meeting prescribed targets of these parameters of a novel method of combining two
      dialyzers in series with two monitors in patients with a large body mass or
      suboptimal vascular access performance. Double dialyzers in parallel are in
      regular use at our center. Tandem use of dialyzers in series with a single
      hemodialysis monitor was frustrated by frequent technical difficulties
      (transmembrane pressure reversal and excessive ultra filtration). We developed a
      technique of using double dialyzers in series to overcome these technical
      difficulties with two monitors and limiting all of the ultrafiltration to the
      second dialyzer. Three patients with A-V grafts and two with catheters had five
      treatments each with single dialyzers, double dialyzers in parallel, and double
      dialyzers in series with two monitors after a washout period encompassing the
      first two sessions in each configuration. Treatment times were set to process
      exactly 85 L of blood in patients with A-V grafts and 60 L in patients with
      catheters. The dosages of heparin and ultrafiltration goals were unchanged during
      the study. In patients with A-V grafts, mean KT/V increased from 1.15 with single
      dialyzers to 1.35 with double parallel (p < 0.02) and 1.48 with tandem (p <
      0.001) dialyzers. %URR (mean) increased from 61.82 for single to 68.32 for double
      parallel (p < 0.05) and 71.38 (p < 0.001) for tandem dialyzers. Tandem dialyzers
      with two monitors achieved insignificantly greater %URR and KT/V compared with
      double parallel dialyzers. The frequency of meeting targets for KT/V improved
      with double parallel and tandem configurations (p < 0.001). Tandem dialyzers were
      more frequently successful in delivering target KT/V (p < 0.05) and target %URR
      (p < 0.001) than double parallel dialyzers. In patients with catheters, neither
      configuration of double dialyzers succeeded in improving %URR, KT/V, or the
      frequency with which targets for these parameters were met. Our method of using
      tandem dialyzers with two monitors is more frequently successful than double
      parallel dialyzers in enhancing delivered KT/V and %URR in patients with A-V
      grafts but not catheters as dialysis access.

PMID- 15745138
TI  - Online conductivity monitoring: validation and usefulness in a clinical trial of
      reduced dialysate conductivity.
AB  - Relatively low dialysate conductivity (Cndi) may improve outcomes by reducing the
      overall sodium burden in dialysis patients. Excess sodium removal, however, could
      lead to hemodynamic instability. We performed a randomized controlled trial of
      reduction of Cndi. For the study, 28 patients were randomized to maintenance of
      Cndi at 13.6 mS/cm (equivalent to 135 mmol/L of Na+) or serial reduction of Cndi
      in steps of 0.2 mS/cm, guided by symptoms and blood pressure. Sodium removal
      estimated from pre- and postplasma concentrations correlated well with removal
      measured by conductivity monitoring as ionic mass balance (R2 0.66, p < 0.0001).
      Of the 16 patients randomized to reduction of Cndi, 6 achieved Cndi 13.4 mS/cm, 6
      achieved 13.2 mS/cm, and 4 achieved 13.0 mS/cm. No episodes of disequilibrium
      occurred. Interdialytic weight gain was reduced from 2.34 +/- 0.10 kg to 1.57 +/-
      0.11 kg (p < 0.0001). Predialysis systolic blood pressure fell from 144 +/- 3 mm
      Hg to 137 +/- 4 mm Hg (p < 0.05). The reduction in convective sodium removal was
      balanced by an increase in diffusive sodium removal (95 +/- 9 mmol cf. 175 +/- 14
      mmol, p < 0.0001). Reduction in Cndi monitored by IMB is safe and practical and
      leads to improved interdialytic weight gains and blood pressure control, while
      avoiding excessive sodium removal.

PMID- 15745139
TI  - Central vein stenosis: a common problem in patients on hemodialysis.
AB  - Central vein stenosis (CVS) has been associated with subclavian (SCV) catheter
      insertions. The prevalence of CVS in the current era with minimal use of SCV
      catheters is unknown. Furthermore, the prevalence of CVS in patients with access
      problems has not been previously described to our knowledge. We evaluated 235
      prevalent patients on hemodialysis (HD), and, of these, 133 underwent venography
      for access related concerns over a 14 month period. Of these 133 patients, 55
      (41%) had evidence of significant CVS on venogram. Patients with CVS had a longer
      duration on HD (43 +/- 12 months vs. 34 +/- 15 months, p = 0.018) and a history
      of a previous HD catheter insertion (52/55 patients vs. 59/78 patients, p =
      0.0039). There were only 18 patients with a subclavian catheter insertion. In
      those with any history of previous HD catheter insertion, multivariate analysis
      demonstrated that number of catheters remains a significant factor (OR 2.69, p =
      0.0004) even after excluding those subclavian insertions. This study demonstrates
      that CVS occurs in almost half of the patients with access problems undergoing
      venography. We confirm the important contribution of central vein cannulation to
      CVS and show that, despite minimizing subclavian catheter insertion, CVS remains
      a relatively common occurrence. Thus further studies should attempt to determine
      the true incidence of this problem and ultimately address the optimal treatment
      strategies.

PMID- 15745140
TI  - Reduction of mitral regurgitation using the Coapsys device: a novel ex vivo
      method using excised recipients' hearts.
AB  - The purpose of this study was to evaluate the ex vivo effects of the Coapsys
      device upon functional mitral regurgitation (MR) in human hearts. We used seven
      excised hearts from patients who underwent cardiac transplantation. All patients
      had functional MR of grade 2 or greater associated with dilated (n = 3) or
      ischemic (n = 4) cardiomyopathy. After the aortic valve was removed, the left
      ventricle was pressurized from the aorta with saline at a constant pressure. The
      degree of MR was then subjectively graded from the opened left atrium (from 0 to
      4). The last three studies included volumetric measurements of MR. By tightening
      the device, the mean MR grade was reduced from 3.3 +/- 0.8 to 1.1 +/- 0.4 (p =
      0.0002). In the quantitative analysis, mean regurgitation volume was reduced from
      1,108 +/- 1,134 ml/min to 236 +/- 89 ml/min (p = not significant). The mitral
      annular septal-lateral dimension decreased from 2.0 +/- 0.3 cm to 1.6 +/- 0.5 (p
      = 0.043). The Coapsys device reduced functional MR in the ex vivo study using
      excised dilated hearts.

PMID- 15745141
TI  - Comparison of different inhalational perfluorocarbons in a rabbit model of acute
      lung injury.
AB  - The purpose of this study was to investigate the influence of different inhaled
      perfluorocarbons (PFC) upon pulmonary mechanics and gas exchange in a saline
      lavage model of acute lung injury. A randomized, controlled animal trial was
      conducted at the university hospital laboratory. Pulmonary gas exchange (pGE),
      static compliance (Cst), and basic hemodynamics (heart rate [HR], arterial [AP]
      and central venous pressures [CVP]) were compared. After induction of lung injury
      by repeated pulmonary lavage with saline solution, 35 New Zealand rabbits (3 +/-
      0.2 kg) were randomized into five groups with seven animals each: 1) conventional
      ventilated control, 2) perfluorooctane (octane), 3) Perflubron
      (perfluorooctylbromide [PFOB]), 4) Perfluoro-1,3,5-trimethylcyclohexane (PP 4),
      and 5) perfluorohexane (hexane). Consecutively, PFC groups were subjected to a
      120 minute study period applying mechanical ventilation (tidal volume of 7 ml/kg)
      in conjunction with PFC performed by a modified halothane vaporizer. Amount of
      vaporization was controlled by weighing the vaporizer at approximately 25 ml/h/kg
      body-weight PFC. Controls remained gas ventilated. After injury, PaO2 was control
      = 53 +/- 13 mbar, octane = 55 +/- 24 mbar, perflubron = 57 +/- 18 mbar, PP4 = 68
      +/- 25 mbar, and hexane = 51 +/- 16 mbar. Within the 120 minute period, PaO2 was
      control = 51 +/- 19 mbar, octane = 42 +/- 6 mbar, perflubron = 40 +/- 11 mbar,
      PP4 = 47 +/- 10 mbar, and hexane = 60 +/- 8 mbar, respectively. At baseline,
      after injury, and throughout the study period, pGE and Cst, as well as HR, AP,
      and CVP, did not significantly differ when compared with octane, PP4, PFOB, and
      controls (p > 0.05), whereas hexane significantly improved pGE and Cst (p <
      0.05). From four different inhaled perfluorocarbons, only perfluorohexane has
      measureable impact upon gas exchange and lung mechanics when compared with a
      conventional lung protective ventilation mode.

PMID- 15745142
TI  - Design and development of an artificial implantable lung using multiobjective
      genetic algorithm: evaluation of gas exchange performance.
AB  - In this study, we constructed an automatic optimization system applying the
      multiobjective genetic algorithm (MOGA) and developed an artificial implantable
      lung possessing antithrombogenicity and high gas exchange performance based upon
      fluid dynamics. This system consists of a three dimenstional CAD system,
      computational fluid dynamics software, and the multiobjective optimization tool
      modeFRONTIER (ESTECO CO., Trieste, Italy). The objectives were to minimize the
      volume of the region having a flow rate of less than 0.5 mm/s by assuming that
      thrombus formation occurs at this limit (ObjTF) and to minimize the standard
      deviation of the flow rate in the hollow fiber to obtain high gas exchange
      performance (ObjGEP). In optimization 1, the arc heights (six variables) and the
      distance between cross-sections (two variables) were used as design variables in
      the inflow and outflow portions. In optimization 2, the edges (two variables) of
      the inflow and outflow portions were optimized in the resulting designs from
      optimization 1. The optimum designs were manufactured using the rapid prototyping
      system and were examined by evaluating gas exchange performance (ObjGEP) in
      vitro. Gas exchange performance increased as the improvement ratio of ObjGEP
      became higher. For the optimum design (improvement ratio of 74.8% for ObjGEP), O2
      transfer increased by an average of 18.4%, and CO2 transfer increased by an
      average of 40.5% when compared with the original design. The results suggest that
      this system was not only effective for reducing the time, cost, and labor of
      developing artificial organs but was also useful as a design and development
      support system for high performance artificial organs for transplantation.

PMID- 15745143
TI  - The impact of heparin coated circuits upon metabolism in vital organs: effect
      upon cerebral and renal function during and after cardiopulmonary bypass.
AB  - During cardiopulmonary bypass (CPB), the brain and the kidneys may be damaged
      because of microemboli, ischemia, and inflammation. The latter has been reduced
      by the use of heparin coated circuits. We questioned whether heparin coated
      circuits could also reduce cerebral and renal damage and whether inflammatory
      markers correlate with damage to the brain and the kidneys. Fifty-one patients
      scheduled for coronary artery bypass grafting were perfused with either a heparin
      coated or an uncoated circuit. To compare the effect of a heparin coated circuit
      with an uncoated circuit upon cerebral and renal function in relation to
      inflammation, we assessed markers of cerebral (S100beta) and renal (N-acetyl-beta
      D-glucosaminidase [NAG], creatinine, and urea) function, inflammation, and oxygen
      metabolism. S100beta levels and NAG levels increased during CPB in both groups as
      compared with baseline levels (p < 0.01), without differences between the groups.
      After 15 minutes on CPB, C4b/c levels were significantly higher in the coated
      group compared with the uncoated group (p < 0.02). C4b/c correlated with S100beta
      (p < 0.01). Total body oxygen delivery (DO2) and consumption (VO2) decreased
      significantly in both groups during CPB (p < 0.01), but recovery was better in
      the coated group. After protamine infusion, total body oxygen delivery and
      consumption correlated negatively with S100beta levels (both p < 0.05) and with
      NAG levels (both p < 0.01). This study suggests that, if adequate tissue
      perfusion is not maintained, the use of a heparin coated circuit gives no
      additional benefit beyond that of the uncoated circuit. The inverse relationship
      of both cerebral and renal markers with DO2 and VO2 suggests that increased
      levels of S100beta and NAG during CPB may primarily be caused by an oxygen
      deficit and secondary to the inflammatory response.

PMID- 15745144
TI  - New method for the detection of thrombus formation in cardiovascular devices:
      optical sensor evaluation in a flow chamber model.
AB  - We proposed a new method of detecting the onset of thrombus formation based upon
      the backscattered light intensity changes caused by the alteration of blood flow
      behavior in the cardiopulmonary devices. In an optical senor based upon the First
      Order Scattering theory, the relationship between the backscattered light
      intensity and hematocrit exhibited a monotonically decaying curve for the
      hematocrit level greater than 45%. To distinguish the effect either by thrombus
      formation or erythrocyte aggregation on the back-scattered light intensity with a
      flow chamber connected to a rabbit arterial-venous bypass model, we generated an
      oscillatory flow using a roller pump and analyzed the results using a Fast
      Fourier Transform (FFT) method. Our hypothesis was that the nonclotting blood
      flow would yield an unchanged fundamental spectral power density of the
      oscillation frequency generated by a roller pump, whereas the thrombus formation
      would attenuate its power. We measured the back-scattered light intensity in the
      flow chamber of high shear region and low shear region (n = 5). The blood flow
      rate was 40 ml/min with the roller pump. The activated clotting time and the
      hematocrit level were adjusted to 170 +/- 10 s with heparin and 35 +/- 5% with a
      phosphate buffered sulfate solution, respectively. As a result, the backscattered
      light intensity from the low shear rate region gradually diminished with time (p
      < 0.05; 0-5 minutes vs. more than 10-15 minutes), whereas that from the high
      shear rate region remained fairly constant. The experimental finding supported
      the hypothesis that the decrease of the backscattered light intensity and
      diminished spectral power density were caused by the aggregation or clotting
      erythrocytes. In conclusion, we found that the measurement of the average
      backscattered light intensity level together with FFT analysis of the
      backscattered light from the flowing blood is a valuable approach in detecting
      the onset of thrombus formation.

PMID- 15745145
TI  - Heterotopic transplantation of the failing rat heart as a model of left
      ventricular mechanical unloading toward recovery.
AB  - The left ventricular assist device (LVAD) is usually used in patients with end
      stage heart failure as a bridge to transplantation. Recently, some studies have
      reported functional recovery with the use of an LVAD, although the mechanisms
      responsible for recovery are not fully understood. We investigated the functional
      recovery of the infarcted, failing rat heart in response to mechanical unloading
      after heterotopic transplantation. Heart failure was induced in Lewis rats by
      ligating the left anterior descending artery. After 4 weeks, the infarcted hearts
      were harvested and heterotopically transplanted. The transplanted infarcted heart
      was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis,
      as well as for mRNA levels encoding for brain natriuretic peptide,
      sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2
      adrenergic receptors. Normal and infarcted rats without transplantation served as
      control animals. The infarcted heart was hypertrophied as evidenced by an
      increase in heart weight and myocyte diameter. After unloading the infarcted
      heart for 2 weeks, there was a decrease in heart weight and myocyte diameter.
      However, the percentage of myocardial fibrosis increased after unloading. The
      mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor
      significantly improved after mechanical unloading. The levels of SERCA2a mRNA
      tended to increase after unloading. In conclusion, unloading the failing,
      infarcted heart can help normalize left ventricular hypertrophy and cardiac gene
      expression. This unloading model appears to partially mimic the conditions of
      hemodynamic support with an LVAD in heart failure patients and potentially offers
      insights into the mechanisms of functional recovery.

PMID- 15745146
TI  - Re: Gregoric ID, Frazier OH, Tamez D, et al: Thrombogenicity of mechanical aortic
      valves in an animal model: site specific testing is crucial. ASAIO J 50: 376-380,
      2004.

PMID- 15745147
TI  - Re: El-Banayosy A, Kizner, L, Shcueler V, Bergmeier S, Dobaugh D, Koerfer R:
      First use of molecular adsorbent recirculation system technique in patients with
      hypoxic liver failure after cardiogenic shock. ASAIO J 50; 332-337, 2004.

PMID- 15745148
TI  - Re: Giridharan GA, Evert DL, Pantalos G.M., et al: Left ventricular and
      myocardial responses to volume unloading and afterload reduction in a computer
      simulation. ASAIO J 50: 512-518, 2004.

PMID- 15745149
TI  - Biapical cannulation for biventricular support with the pneumatically driven
      Excor system.
AB  - We report on a 41-year old patient who underwent implantation of an Excor
      biventricular assist system. Both ventricles were cannulated on the apical aspect
      with left ventricular apex cannulas. The cannulation technique is described.

PMID- 15745150
TI  - An introduction to Project Bionics' "guide to collections relating to the history
      of artificial organs".

PMID- 15745151
TI  - [TLR family and viral infection].
AB  - The immune system has been divided into innate and adaptive component, each of
      which has different roles and functions in defending the organism against foreign
      agents, such as bacteria and viruses. An important advance in our understanding
      of early events in microbial recognition and subsequent development of immune
      responses was the identification of Toll-like receptors (TLRs) as key molecules
      of the innate immune systems. The family of TLRs in vertebrates detects conserved
      structures found in a broad range of pathogens and triggers innate immune
      responses. At present, 11 members of the TLR family have been identified. A
      subset of TLRs recognize viral components and induce antiviral responses by
      producing type I interferons. Recent accumulating evidence has clarified
      signaling pathways triggered by TLRs in viral infection.

PMID- 15745152
TI  - [Recognition of virus infected cells by NK cells].
AB  - NK cells show cytotoxicity against virus-infected cells and tumor cells and play
      an important role in host defense. Although mecheanism of target cell recognition
      by NK cells have been unclear for a long time, it has recently been elucidated
      that certain NK cell receptors specifically recognize virus products.
      Furthermore, expression pattern of NK cell receptors, which consist of activating
      and inhibitory receptors, determines susceptibility to virus-infection. Here, we
      review recent progress of mechanism of recognition of virus-infected by NK cells.

PMID- 15745153
TI  - [Virus-induced expression of type I interferon genes].
AB  - Intracellular double-stranded (ds) RNA is a major sign of replication for many
      viruses. Host mechanisms detect the dsRNA and provoke antiviral responses.
      Recently, we identified retinoic acid inducible gene-I (RIG-I), which encodes a
      DExD/H box RNA helicase containing the caspase recruitment domain (CARD) as a
      critical regulator for dsRNA-induced signaling. The helicase domain with intact
      ATPase activity is responsible for recognition of dsRNA, and the CARD transmits
      downstream signals, resulting in the activation of genes including type I
      interferons. In this review, we discuss the function of RIG-I in antiviral innate
      immunity.

PMID- 15745155
TI  - [Sendai virus proteins counteracting the host innate immunity].
AB  - The nucleotide sequence of Sendai virus (SeV) genome was determined in the
      1980's. During the analysis of its cDNA, two mRNAs were found to be transcribed
      from the P gene; one encoding P protein, the other encoding V protein. In
      addition, C protein was found to be translated from both/ mRNAs. Though the
      function of V and C proteins was being unknown for a while, the reverse-genetic
      technique of paramyxoviruses developed at the latter half of the 1990's gave the
      light on studying them. The V or C protein-knockout-SeV can be made successfully,
      indicating that the V and C proteins are nonessential for virus growth, However,
      V knockout-SeV was cleared from the mouse lungs at the one day post inoculation,
      and C knockout-SeV was cleared immediately after the inoculation. Both V and C
      proteins were thus appeared to be important for counteracting host innate
      immunity generated in the early phase of viral infection.

PMID- 15745154
TI  - [Molecular mechanisms for suppression of interferon signal transduction pathways
      caused by viral infections].
AB  - In order to establish infection to host cells, viruses suppress or escape from
      the host immune response against microorganisms by various strategies. Interferon
      (IFN) system is an important contributor of innate immunity. IFN is induced by
      viral infection, and it promotes antiviral state through induction and/or
      activation of the effector molecules. Many viruses possess the suppression or
      inhibition mechanisms for the anti-viral effector molecules, whereas they also
      perform inhibition of IFN signaling pathway, JAK/STAT pathway. We consider that
      latter is a most effective strategy counteracting IFN function, because the
      signaling pathway is an entrance of the system. The strategies counteracting
      JAK/STAT pathway are varied among virus species. Viruses perform (i) production
      of IFN-binding protein, (ii) degradation of JAK/STAT components, (iii)
      suppression of activation (phosphorylation) of the components, (iv) inhibition of
      nuclear translocation of activated transcription factor, and (v) induction of
      host JAK/STAT negative regulator. Here, we present these strategies, especially
      our recent resulta of HSV1, mumps virus, and measles virus. For example, HSV1
      induces a host JAK/STAT negative regulator SOCS3 (suppressor of cytokine
      signaling-3). Mumps virus V protein promotes degradation of both STAT-1 and STAT
      3. Measles virus freezes the flexibility of IFN-alpha receptor complex by the
      action of viral proteins, C and V.

PMID- 15745156
TI  - [Expression of host genes in influenza virus infected cells].
AB  - The NS1 protein of influenza virus shuts off host gene expression by inhibiting
      the polyadenylation-site cleavage of host pre-mRNAs, resulting in a general
      decline in cellular protein synthesis. On the other hand, an activation of
      several host genes related to host antiviral defense such as interferon-
      alpha/beta, MxA, 2',5'-oligoadenylate synthetase, and Fas occures upon infection.
      Therefore, balance of the shut-off and the activation of cellular genes during
      virus growth may be crucial in determining the outcome of infection. To obtain a
      comprehensive view of the global effects of influenza virus infection on human
      respiratory epithelial cells at the cytoplasmic mRNA level, we performed oligo
      DNA microarray analysis using GeneChip arrays (Affymetrix). In NCl-H292 cells
      infected with A/Udorn/72 virus, more than 4-fold increase of expression level was
      observed for 164 genes at 12 h pi. Approximately 60% of the virus-stimulated
      genes (VSGs) were also stimulated with interferon-beta treatment and contained
      the genes known to possess antiviral activity. Interestingly, majority of the
      VSGs were stimulated before induction of interferons, suggesting that the
      stimulation of the VSGs during early phase of infection is not mediated by
      interferons, but it is triggered from within by the virus infection.

PMID- 15745157
TI  - [Mechanism of persistence in HCV infection].
AB  - One of the prominent features of hepatitis C virus (HCV) is persistent infection,
      which is assumed to be a crucial event as a result of evading host defense
      system. Type I interferon beta (IFN- beta) system is induced rapidly after viral
      infection and plays a central role in innate immunity. Upon immediate induction
      of type I IFN as host first defense line, interferon regulatory factor-3 (IRF-3)
      is phosphorylated, formed of homodimer and translocates to nucleus. IFN-beta
      induction due to new castle disease virus (NDV) was significantly decreasd after
      the expression of full HCV genome (HCR6-Rz). Similar modification was observed in
      cell line expressing core to the NS2 protein region (HCR6-Fse). However, this
      decreasing was not observed in cell line expressing NS2 to the NS5B region (HCR6
      Age). IRF-3 dimer formation induced by NDV infection was also suppressed after
      the expression of HCR6-Rz and HCR6-Fse, but not HCR6-Age. We further analyzed
      using transiently expressed HCV core, E1 or E2 in HepG2 cells. The suppression of
      IRF-3 dimer formation was caused by HCV core protein alone. These results
      indicated that a new crucial biological function of HCV core protein that may be
      related to persistence and pathogenesis of HCV.

PMID- 15745158
TI  - [Molecular mechanism of tissue-specific infection of poliovirus].
AB  - Poliovirus is the causative agent of an acute disease of the central nervous
      system, poliomyelitis. Poliovirus will be eradicated in the near future by a
      world-wide vaccination program. Poliovirus is a neurotropic virus that produces
      severe lesions selectively in the CNS. However, a basic question why poliovirus
      exhibits neurotropic property has not been elucidated. Poliovirus receptor and
      host factors involved in the translation initiation of viral protein, which are
      required for virus replication, play important roles in determining tissue
      tropism. We found that type I interferon response is also an important
      determinant of poliovirus tissue tropism. Type I interferon inhibits viral
      replication in the non-target tissues. The tissue tropism of poliovirus may be
      determined based on the balance of these mechanisms.

PMID- 15745159
TI  - [Rabies and other lyssaviruses].
AB  - Since rabies has not been reported in Japan for nearly the past 50 years, it has
      been relegated to the status of a forgotten infectious disease in this country.
      However,in the neighboring Asian countries, Africa, America, the number fo rabies
      cases had not decrease but on the contrary, seen an increasing trend. In Russia
      and the former Soviet Union countries (CIS countries), the number of information.
      Between 30,000 approximately 20,000 fatal cases of rabies in both humans and
      animals had been reported yearly butit was thought that the number might run up
      to hundred of thousands.japan, Taiwan, UK, Australia and New Zealand are rabies
      free countries and should be considered the exception rather than the norm. Due
      to the long Lull in which rabies has not occurred in Japan,people tend to forget
      that the disease can infect all mammals including humans, with a mortality rate
      of 100% after manifestation of debilitating nervous symptoms and that is one of
      the most dangerous zoonotic viral diseases on earth.

PMID- 15745160
TI  - [Crimean-Congo hemorrhagic fever].
AB  - Crimean-Congo hemorrhagic fever (CCHF) is an acute infectious disease caused by
      CCHF virus (CCHFV), a member of the family Bunyaviridae, genus Nairovirus. The
      case fatality rate of CCHF ranges from 10-40%. Because CCHF is not present in
      Japan, many Japanese virologists and clinicians are not very familiar with this
      disease. However, there remains the possibility of an introduction of CCHFV or
      other hemorrhagic fever viruses into Japan from surrounding endemic areas.
      Development of diagnostic laboratory capacity for viral hemorrhagic fevers is
      necessary even in countries without these diseases. At the National Institute of
      Infectious Diseases, Tokyo, Japan, laboratory-based systems such as recombinant
      protein-based antibody detection, antigen-capture and pathological examination
      have been developed. In this review article, epidemiologic and clinical data on
      CCHF in the Xinjiang Uygur Autonomous Region, compiled through field
      investigations and diagnostic testing utilizing the aforementioned laboratory
      systems, are presented. CCHFV infections are closely associated with the
      environmental conditions, life styles, religion, occupation, and human economic
      activities. Based on these data, preventive measures for CCHFV infections are
      also discussed.

PMID- 15745161
TI  - [Rift Valley fever virus].
AB  - Rift Valley fever virus (RVFV) causes massive mosquito-borne epidemics among
      humans and decimates ruminants in which the mortality rate is about 1% and 10
      30%, respectively. Morbidity in RVFV-infected humans is high largely due to the
      effects of hemorrhagic fever and encephalitis. This virus is native to sub
      Saharan Africa; yet if this virus is introduced into the environment, virus
      transmission appears to occur whenever sheep and cattle are present with abundant
      mosquito populations. RVFV is a negative-strand RNA virus which belongs to the
      family Bunyaviridae, genus Phlebovirus, and contains tripartite-segmented genomes
      (S, M, and L). S-segment is the ambisense genome, where N and NSs genes are coded
      in an antiviral-sense and viral sense S-segment, respectively. The inhibition of
      host mRNA synthesis, which is induced by the binding of NSs protein to RNA
      polymerase II transcription factor TFIIH, is the primary reason for the host
      protein shut-off in RVFV-infected cells. Development of a RVFV reverse genetics
      system, which has not been accomplished yet, is important for the study of viral
      replication mechanisms, host virus interaction, viral pathogenicity as well as
      vaccine evaluation and development.

PMID- 15745162
TI  - [Nipah virus infection].
AB  - Nipah virus (NiV), emerged in Peninsular Malaysia, caused an outbreak of severe
      febrile encephalitis in humans and respiratory diseases in pigs between 1998 and
      1999. By May of 1999, the death of 105 humans and the culling of about 1.1
      million pigs were reported. Fruitbats of Pteropid species were identified as the
      natural reservoir hosts. The epidemiological studies suggested that NiV was
      introduced into pig farms by fruitbats, and was than transmitted to humans
      (mainly pig farmers) and other animals such as dogs, cats and horses. In 2004,
      NiV reappeared in Bangladesh with greater lethality. In contrast to the Malaysia
      case, epidemiologic characteristics of this outbreak suggested the possibility of
      fruitbats-to-person, or person-to-person transmission. In this article, the
      epidemiological comparison between two outbreaks in Malaysia and Bangladesh, and
      the new-trends of virological studies of NiV will be discussed.

PMID- 15745164
TI  - [Amendment to the infectious disease control law].
AB  - The Law Concerning the Prevention of Infectious Diseases and Medical Care for
      Patients of Infections (the Infectious Diseases Control Law) enacted on April 1,
      1999, accompanies an additional rule for reconsideration in five years after
      putting the law in operation and for taking necessary steps when needed. The
      responses against bioterrorism involving anthrax and smallpox after the terrorist
      attacks on September 11, 2001, in the United States of America (a notice on
      October 11, 2001 by the Tuberculosis and Infectious Diseases Control Division,
      MHLW) and the response to severe acute respiratory syndrome (SARS), an emerging
      infectious disease upon which a Global Alert was issued on March 12, 2003, by
      WHO, were discussed. On November 5, 2003, partial amendment of the Infectious
      Diseases Control Law and the Quarantine Law was approved and put into operation
      on. In the present amendment, the following three points were principally
      reconsidered: 1. strengthening infectious disease control in an emergency,
      particularly the role of national government, 2. reviewing control strategy of
      infectious diseases of animal origin, and 3. reviewing target diseases of the
      Infectious Diseases Control Law and categories of infectious diseases.

PMID- 15745163
TI  - [Recent topics on hepatitis E virus: emerging, zoonotic, and animal-to-human
      transmission in Japan].
AB  - Hepatitis E is undoubtedly a zoonosis. Recent observations suggest that the
      zoonotic food-borne mode of transmission has played an important role in the
      spread of hepatitis E virus (HEV) among Japanese people (who in general likes
      eating everything uncooked or undercooked: Sushi, Sashimi, Tataki, Namagimo,
      Shabu-shabu, etc). Moreover, the situation seems to be worsening. Wild boar (and
      deer also) has recently been increasing in its number, becoming a more potent HEV
      reservoir to humans than before. Pork, replacing beef in people's recent fear of
      BSE, is being consumed increasingly, particularly in Hokkaido. It may be Japanese
      people that an effective HEV vaccine is most longed for by.

PMID- 15745165
TI  - [BAC system: A novel method for manipulation of herpesvirus genomes based on
      bacterial genetics].
AB  - Although methods for reverse genetics of herpesviruses have been established in
      early 1980s, the steps are laborious and time-consuming. In 1997, Dr.
      Koszinwski's group reported a novel approach for the construction of herpesvirus
      mutants, based on cloning the viral genome as a bacterial artificial chromosome
      (BAC) in E. coli. This technique allows the maintenance of viral genomes as
      plasmid in E. coli and the reconstitution of viral progeny by transfection of the
      BAC plasmid into eukaryotic cells. Any genetics modification of the viral genome
      in E. coli using bacterial genetics is possible, thereby facilitating the
      introduction of mutagenesis into herpesvirus genome. This 'BAC system' has opened
      new avenues for reverse and forward genetics of herpesviruses in basic research
      and in vector development for human therapy. Here we describe the principle of
      the 'BAC system' in herpesvirus researches.

PMID- 15745166
TI  - [Should patients after radical surgery for colorectal cancer be followed up?].

PMID- 15745167
TI  - [Type 2 diabetes in children and adolescents].

PMID- 15745168
TI  - [Back pain and the workplace].

PMID- 15745169
TI  - [H. pylori eradication therapy compared with antisecretory non-eradication
      therapy for the prevention of recurrent bleeding stomach ulcer].

PMID- 15745170
TI  - [Eradication therapy for peptic ulcer disease in Helicobacter pylori positive
      patients].

PMID- 15745171
TI  - [Follow-up of patients after radical surgery for colorectal cancer].

PMID- 15745172
TI  - [Laparoscopic operation for paraesophageal hernia].

PMID- 15745173
TI  - [Psychiatric patients' perception of shielded units].

PMID- 15745174
TI  - [Need of and searching for information by patients with acute myeloid leukemia
      undergoing intensive therapy].

PMID- 15745175
TI  - [Natural bleeding patterns in pre- and perimenopausal women--secondary
      publication].

PMID- 15745176
TI  - [Frequency of postmenopausal bleedings--secondary publication].

PMID- 15745177
TI  - [Childhood asthma in clinical practice].

PMID- 15745178
TI  - [Mucocele of the appendix].

PMID- 15745179
TI  - [Development of tuberculosis after treatment with the TNF-alpha inhibitor
      infliximab].

PMID- 15745180
TI  - [Simultaneous presence of Takayasu's arteritis and factor V Leiden
      thrombophilia].

PMID- 15745181
TI  - [Better endoscopic treatment of bleeding ulcer].

PMID- 15745182
TI  - [Historical introduction of pole-walking as a therapeutic and a preventive
      measure].

PMID- 15745183
TI  - [Abuse of psychiatry].

PMID- 15745184
TI  - [History of psychiatry 2005].

PMID- 15745185
TI  - [Agger doesn't see the progress].

PMID- 15745186
TI  - [The National Board of Health and Welfare's dimensioning is not based on health
      services needs].

PMID- 15745187
TI  - [Geriatrics battling against odds--new specialist education and structure
      reform].

PMID- 15745188
TI  - Chasing ideas: clinical research in the NHS.

PMID- 15745189
TI  - Audit, assessment or performance management?

PMID- 15745190
TI  - Anticipating, preventing and investigating medication errors.

PMID- 15745191
TI  - Adjusting therapeutic dosage regimens to optimise the balance of benefit to harm.

PMID- 15745192
TI  - Adverse drug interactions.

PMID- 15745193
TI  - Anticipating, investigating and managing the adverse effects of drugs.

PMID- 15745194
TI  - Rational prescribing: the principles of drug selection and assessment of
      efficacy.

PMID- 15745195
TI  - Over-regulation of clinical research: a threat to public health.
AB  - Clinical research is subject to increasing regulation by research ethics
      committees and research and development offices which are responding to social
      and political pressures, as well as to new legislation, both European and
      national, some of which is still being worked out. The resulting bureaucracy,
      expense and confusion are putting insuperable hurdles in the way of clinical
      research and clinical care is compromised. What research is still possible will
      only be done in large organisations and may even be seriously biased. The
      solutions are to inform and seek the help of the public and to forge alliances
      with patient groups. Patients have far more to lose than clinical researchers
      who, if clinically qualified, can more easily pursue a fulfilling career as
      clinicians rather than researchers.

PMID- 15745196
TI  - Academic clinical research in the new regulatory environment.
AB  - As a result of European legislation passed in 2001 (Directive 2001/20/EC), all
      clinical trials, whether sponsored by industry, a major national body or charity,
      or done by a single academic investigator, must get approval from the Medicines
      and Healthcare products Regulatory Agency (MHRA) as well as obtaining ethical
      approval. This requires all studies to be carried out to the standards of 'Good
      Clinical Practice' and places burdens on investigators in terms of reporting
      adverse events and archiving. A new directive has been published in draft form
      that will finally define what is meant by Good Clinical Practice in Europe.

PMID- 15745198
TI  - The RCP Information Laboratory (iLab): breaking the cycle of poor data quality.
AB  - A review of data quality in the NHS by the Audit Commission cited a lack of
      clinician involvement in the validation and use of centrally held activity data
      as one of the key issues to resolve. The perception that hospital episode
      statistics cannot support the needs of the individual clinician results in
      mistrust and disinterest. This in turn leads to under-development of such data
      from a clinical perspective, and the cycle continues. The RCP Information
      Laboratory (iLab) aims to address this problem by accessing, analysing and
      presenting information from these central repositories concerning the activity of
      visiting individual consultant physicians. With support from iLab staff--an
      information analyst and a clinician--local data quality issues are highlighted
      and local solutions sought. The information obtained can be used as an objective
      measure of activity to support the processes of appraisal and revalidation.

PMID- 15745197
TI  - Research networks for stroke rehabilitation: opportunities and barriers.
AB  - The previous negative attitude to stroke care is gradually giving way to a more
      positive approach, stimulated by a growing evidence base and policy initiatives
      such as the requirement that stroke units be established in all district general
      hospitals. There is now a new opportunity to link groups of stroke units into
      research networks to support the implementation of multi-centre trials. Such
      trials have the potential to increase patient recruitment rates, and will enhance
      the generalisability of the findings. Recent experience in establishing a stroke
      rehabilitation research network is reported in this paper.

PMID- 15745199
TI  - Implications of the new GP contract.
AB  - A new contract for general practitioners (GPs) was introduced in the UK on 1
      April 2004 which has implications for secondary care. In particular, the contract
      means that GPs can opt out of out-of-hours care, and accident & emergency
      services have voiced their concern that their workload may increase as a result.
      The new contract provides the potential for a rise in GPs' salaries by two means:
      through the provision of the Quality and Outcomes Framework which includes the
      management of 10 common chronic diseases; and through 'Enhanced Services', which
      are a series of optional 'extra' more specialised services with national
      specified standards that can be commissioned by primary care organisations
      (PCOs).

PMID- 15745200
TI  - Prevalence of primary hyperaldosteronism assessed by aldosterone/renin ratio and
      spironolactone testing.
AB  - Recent studies have suggested that primary hyperaldosteronism may be present in
      more than 10% of patients with hypertension. We aimed to estimate the prevalence
      in unselected patients in primary care, and investigate the influence of current
      drug treatment upon the aldosterone/renin ratio (ARR) and its prediction of blood
      pressure response to spironolactone. We measured blood pressure, plasma
      electrolytes, renin activity and aldosterone in 846 patients with hypertension.
      Spironolactone 50 mg was prescribed for one month to patients with blood pressure
      > or = 130/85 mmHg and ARR > or = 400. The primary outcome measure was to
      discover the proportion of patients with plasma aldosterone > or = 400 pmol/l and
      ARR > or = 800 and either an adrenal adenoma on computed tomography scan or a
      systolic blood pressure response to spironolactone > or = 20 mmHg. Only one
      patient had an adenoma, and only 16 (1.8%) had both a plasma aldosterone > or =
      400 pmol/l and ARR > or = 800. By contrast, 119 patients (14.1%) had an elevated
      ARR but normal plasma aldosterone. In 69 patients out of the 119 who received
      spironolactone, blood pressure fell by 26/11 mmHg. These patients were
      normokalaemic but had uncontrolled hypertension despite multiple drugs. The
      response to spironolactone was best predicted by a low plasma renin, < or = 0.5
      pmol/ml/h (<10 mU/l), despite treatment with an ACE inhibitor. We concluded that
      adrenal adenomas are an uncommon cause of hypertension. In the absence of
      hypokalaemia, a low plasma renin is a sufficient and simple way of detecting
      spironolactone-responders among patients with resistant hypertension. Only
      patients with both hypokalaemia and low plasma renin, measured while the patient
      is off beta blockade, require measurement of aldosterone. A plasma aldosterone
      >400 pmol/l together with renin activity < or = 0.5 pmol/ml/h should trigger
      further investigations for an adrenal adenoma.

PMID- 15745201
TI  - Three oncologists by Ken Currie.
AB  - This commissioned work was painted by the contemporary artist, Ken Currie. Like
      much modern art, it is more challenging to the viewer than classical
      representational depictions of doctors. Such art can also reflect more of the
      artist's own philosophy and beliefs.

PMID- 15745202
TI  - Sex is dangerous.
AB  - Infectious diseases with high mortality, disability and creating public anxiety
      are not new, but despite this our initial responses to HIV/AIDS have been
      primitive and slow. Since the start of the epidemic over 60 million people
      throughout the world have been infected, with the main focus of the epidemic
      currently in Sub-Saharan Africa. However, there is every indication that the
      epidemic will move more towards South-East Asia, with increasing numbers in India
      and China. Infection with HIV has a profound effect on individuals and their
      families, and can also lead to destabilisation of societies through its effects
      on the economy, institutions and security. Considerable emphasis has been placed
      recently on the widespread use of anti-retroviral therapy. This is a worthwhile
      initiative but is only part of a balanced array of approaches, which requires
      building a political consensus, social economic interventions and modifying the
      biology. Strong political leadership is still required, with an approach that
      recognises that the socioeconomic drivers of this epidemic.

PMID- 15745203
TI  - Drug misuse: a review of treatments.
AB  - Treating drug users is something that every health professional should be able to
      do, whether providing brief interventions or harm minimisation advice or
      providing an assessment and directing the user for further care. Unfortunately,
      despite a growing problem, few health professionals outside specialist addiction
      services have the skills, experience and knowledge to provide patients with
      effective pharmacological interventions. Many of the pharmacological treatment
      options, such as methadone maintenance, have had extensive research and have been
      shown to be effective in a number of outcome areas. Newer treatments, such as
      buprenorphine- and naltrexone-assisted detoxification have a growing research
      base. This article provides a brief overview of treatments options and the impact
      of drug use on social and medical care services.

PMID- 15745204
TI  - Nutrition--who cares?

PMID- 15745205
TI  - Assisted Dying for the Terminally Ill Bill, 2004.

PMID- 15745206
TI  - Assisted Dying for the Terminally Ill Bill, 2004.

PMID- 15745207
TI  - Assisted Dying for the Terminally Ill Bill, 2004.

PMID- 15745208
TI  - Assisted Dying for the Terminally Ill Bill, 2004.

PMID- 15745209
TI  - The management of rare diseases.

PMID- 15745210
TI  - Influence of guidelines on CPR decisions.

PMID- 15745211
TI  - Influence of guidelines on CPR decisions.

PMID- 15745212
TI  - Symptoms and perceptions of disease.

PMID- 15745213
TI  - Team working.

PMID- 15745214
TI  - Fluid, electrolytes and nutrition.

PMID- 15745215
TI  - Cannabis--the right decision but the wrong way to go about it?

PMID- 15745216
TI  - Effects of sub-minimum inhibitory concentration antibiotic levels and temperature
      on growth kinetics and outer membrane protein expression in Mannheimia
      haemolytica and Haemophilus somnus.
AB  - The objective of this study was to determine the effects of sub-minimum
      inhibitory concentrations (sub-MICs) of 2 veterinary antibiotic preparations,
      chlortetracycline (CTC) and chlortetracycline-sulfamethazine (CTC + SMZ), on
      growth kinetics and outer membrane protein expression in Mannheimia haemolytica
      and Haemophilus somnus at normal and febrile body temperatures. Sub-minimum
      inhibitory concentrations of both antibiotics reduced the growth rates of M.
      haemolytica and H. somnus. Growth of both species was not inhibited when grown at
      41 degrees C compared to 37 degrees C. There was no detectable consistent effect
      of antibiotic or temperature on outer membrane protein expression for either
      species. Our study indicates that sub-MIC levels of CTC and CTC + SMZ markedly
      impair growth of clinical M. haemolytica and H. somnus isolates, potentially
      allowing more effective host clearance during infection.

PMID- 15745217
TI  - Effect of a trivalent vaccine against Staphylococcus aureus mastitis lymphocyte
      subpopulations, antibody production, and neutrophil phagocytosis.
AB  - The effect of a novel bovine mastitis trivalent vaccine, containing
      Staphylococcus aureus capsular polysaccharide type 5 (T5), 8 (T8), and 336
      (T336), on lymphocyte subpopulations, antibody production, and neutrophil
      phagocytosis was evaluated. Twenty pregnant heifers were immunized with either
      the trivalent alone, trivalent emulsified in Freund's incomplete adjuvant (FICA),
      trivalent in aluminum hydroxide, or adjuvant only (FICA). Immunization was done
      30 d before the expected calving date followed by 2 boosts in a 2-week interval.
      Compared to FICA, serum antigen-specific immunoglobulin (Ig)G1 and IgG2 were
      significantly increased in all the vaccinated groups before parturition and
      sustained until 3 wk postpartum. In comparison with the trivalent alone,
      formulation with either adjuvant enhanced production of IgG2, but not IgG1.
      Immune sera, which contained the highest amount of antibodies, slightly increased
      neutrophil phagocytosis to the 3 serotypes of killed S. aureus, but most of the
      differences were not significant due to large variation between the cows. The
      percentage of CD4+ lymphocyte was significantly higher in vaccinated groups than
      that of FICA 4 wk after the primary immunization. In comparison with FICA, cows
      inoculated with trivalent vaccine and adjuvants had an increased percentage of
      CD8+ lymphocytes at 2 time points, 2 wk before and after calving. Our results
      indicated that the whole cell trivalent vaccine, with or without adjuvants, is
      able to elicit antibody responses specific to the 3 capsular polysaccharide
      antigens. The increase of T8-specific IgG2 was more noticeable when the vaccine
      was emulsified with adjuvants.

PMID- 15745218
TI  - A temporal-spatial analysis of bovine spongiform encephalopathy in Irish cattle
      herds, from 1996 to 2000.
AB  - This study investigated the distribution of bovine spongiform encephalopathy
      (BSE) in herds of cattle in Ireland over the years 1996 through 2000, prior to
      the introduction of widespread active surveillance. Mappings of index herds, herd
      density, and standardized morbidity ratios, by county, were employed to help
      visualize areas of potential clustering of BSE. The hypothesis of spatial
      clustering was tested using a spatial scan statistic applied to the location of
      the herd where exposure likely occurred. Both Bernoulli and Poisson spatial
      models indicated marked clustering of BSE herds centred on Monaghan county, with
      secondary clusters detected by Bernoulli approaches and some Poisson models in
      Wexford and Cork. The number of cases increased with time, but clear temporal
      spatial clusters were rarely detected, except in the case of a cluster in
      Wexford. The focussed spatial scan analyses using the location of large-scale
      feed suppliers provided support for the hypothesis that clustering of BSE may be
      associated with feed source. The results of our analyses provided strong evidence
      in support of the hypothesis that herds, in which animals were most likely to
      have been exposed to the BSE agent, cluster geographically.

PMID- 15745219
TI  - Mixed models applied to the study of variation of grower-finisher mortality and
      culling rates of a large swine production system.
AB  - Large scale production systems for swine are frequently organized in a
      hierarchical structure. Consequently, important production parameters, such as
      mortality and culling, can be analyzed at different levels. The major aims of
      this study were to assess variance components (VC) of mortality and culling rates
      attributed to sites and to barns within a site, and subsequently to investigate
      the impact of average entry weight, days on feed (length of the production turn),
      and season on the magnitude of the VC. Then, data from a large farm with 3 sites
      were collected during 5 y. In total, 1720040 pigs distributed in 1502 all-in/all
      out grower-finisher groups were included. Linear mixed models were fitted for
      mortality and culling rates. The barn was modeled as the residual component (barn
      to-barn variations) with production turn and site nested within production turn
      as random intercept variance components. Barn-to-barn pig group variation was the
      largest VC for mortality (63.08%), when no predictors were included in the
      models. Predictors, such as pigs placed on quarters 2 and 3, low average entry
      weight, and shorter production turn length, were associated together with higher
      mortality. The explained proportion of variance due to these predictors was about
      12.05% and the VC for barn, site, and production turn were 67.6%, 17.6%, and
      14.8%, respectively. Barn-to-barn variation was also the largest VC for culling
      rate (46.2%), but the same predictor mentioned above explained only about 1.4% of
      the variation. The VC for barn, site, and production turn were 46.8%, 21.3%, and
      31.8%, respectively. Since the variability among barns far exceeded the
      variability among sites, the barn should be used as experimental unit in studies
      with grower-finisher mortality, culling rate, or both, as outcome variables.

PMID- 15745220
TI  - Mycobacterium avium subsp. paratuberculosis from free-ranging deer and rabbits
      surrounding Minnesota dairy herds.
AB  - The objectives of this study were to estimate the prevalence of Mycobacterium
      avium subsp. paratuberculosis (MAP) among deer and rabbits surrounding infected
      and noninfected Minnesota dairy farms using fecal culture, and to describe the
      frequency that farm management practices were used that could potentially lead to
      transmission of infection between these species. Fecal samples from cows and the
      cow environment were collected from 108 Minnesota dairy herds, and fecal pellets
      from free-ranging white-tailed deer and eastern cottontail rabbits were collected
      from locations surrounding 114 farms; all samples were tested using bacterial
      culture. In addition, a questionnaire was administered to 114 herd owners. Sixty
      two percent of the dairy herds had at least 1 positive fecal pool or
      environmental sample. A total of 218 rabbit samples were collected from 90% of
      the herds, and 309 deer samples were collected from 47% of the herds. On 2 (4%)
      of the farms sampled, 1 deer fecal sample was MAP positive. Both farms had
      samples from the cow fecal pool and cow environment that were positive by
      culture. On 2 (2%) other farms, 1 rabbit fecal sample was positive by culture to
      MAP, with one of these farms having positive cow fecal pools and cow
      environmental samples. Pasture was used on 79% of the study farms as a grazing
      area for cattle, mainly for dry cows (75%) and bred or prebred heifers (87%). Of
      the 114 farms, 88 (77%) provided access to drylot for their cattle, mainly for
      milking cows (77/88; 88%) and bred heifers (87%). Of all study farms, 90 (79%)
      used some solid manure broadcasting on their crop fields. Of all 114 farms, the
      estimated probability of daily physical contact between cattle manure and deer or
      rabbits was 20% and 25%, respectively. Possible contact between cattle manure and
      deer or rabbits was estimated to occur primarily from March through December. The
      frequency of pasture or drylot use and manure spreading on crop fields may be
      important risk factors for transmission of MAP among dairy cattle, deer, and
      rabbits. Although the MAP prevalence among rabbits and deer is low, their role as
      MAP reservoirs should be considered.

PMID- 15745221
TI  - Comparison of morphology, viability, and function between blood and milk
      neutrophils from peak lactating goats.
AB  - The morphological features of blood and milk neutrophils from peak lactating
      goats were compared using light microscopy, scanning electron microscopy and flow
      cytometry in order to investigate the cytological changes of neutrophils after
      migration into the mammary gland. The kinetics of reactive oxygen intermediates
      (ROI) generation and gelatinase release of blood and milk neutrophils, with or
      without stimulation of phorbol 12-myristate, 13-acetate ester (PMA), were used to
      characterize their responses to inflammatory stimuli. Neutrophils isolated from
      goat milk were highly segmented and contained multi-lobed nuclei.
      Ultrastructurally, milk neutrophils were more ruffled on the surface compared to
      blood neutrophils. Approximately 30% of milk neutrophils were undergoing cell
      death, either necrosis or apoptosis, in contrast to 8% of blood neutrophils. The
      ROI production of activated milk neutrophils peaked earlier than blood
      neutrophils, but the duration and the intensity were much less. Neutrophils from
      both sources augmented the release of gelatinase in response to PMA (1 ng/mL).
      However, the amount of gelatinase released from milk neutrophils was lower (P <
      0.05) than that of blood neutrophils. In summary, more neutrophils become
      apoptotic and necrotic in the mammary gland, presumably due to spontaneous aging,
      the process of diapedesis, and the interaction with milk components. Milk
      neutrophils have impaired functionalities in comparison with blood neutrophils.
      The information is relevant when studying mammary gland immunity and related
      diseases, such as mastitis.

PMID- 15745222
TI  - Neuronal nitric oxide synthase is heterogeneously distributed in equine myofibers
      and highly expressed in endurance trained horses.
AB  - Mammalian skeletal muscle expresses splice variants of neuronal nitric oxide
      synthase (nNOS). Skeletal muscles have a metabolically heterogeneous population
      of myofibers, and fiber composition in equine skeletal muscle is correlated with
      athletic ability in endurance events. In this study, we investigated whether nNOS
      expression in equine skeletal muscle is related to fiber type and endurance
      training. Biopsy samples obtained from the gluteus medius of sedentary- (SH) and
      endurance-trained (TH) horses were examined for the electrophoretic mobility of
      myosin heavy chain (MHC) and NOS activity. Serial tissue cross-sections were
      stained for myosin ATPase and nicotinamide adenine dinucleotide (NADH) reductase,
      and also immunostained for nNOS. The gluteus medius of TH had higher levels of
      nNOS expression and activity when compared to muscle from SH. In SH, nNOS was
      restricted to the subsarcolemmal area while in TH nNOS was also present at
      cytoplasmic sites. A splice variant of nNOS was heterogeneously distributed among
      the different myofibers, its expression being higher in fast-oxidative-glycolytic
      type IIA fibers than in fast-glycolytic type IIX fibers and absent in slow-twitch
      type I fibers. Trained horses had a significantly higher relative content of type
      IIA fibers, a greater oxidative capacity, and a lower percentage of type IIX
      fibers when compared with SH. The differences in muscle fiber typing between the
      2 groups of horses reflected alterations that probably resulted from the
      endurance-training program. Overall, these results show that nNOS is
      differentially expressed and localized in the gluteus medius according to the
      fiber type and the athletic conditioning of the horses.

PMID- 15745224
TI  - An evaluation of thermo-assisted drying and decontamination for the elimination
      of porcine reproductive and respiratory syndrome virus from contaminated
      livestock transport vehicles.
AB  - The purpose of this report is to validate a new protocol, the thermo-assisted
      drying and decontamination (TADD) system, for eliminating porcine reproductive
      and respiratory syndrome virus (PRRSV) from contaminated transport vehicles.
      Scale models of weaned pig trailers were used. The principle of TADD is to raise
      the interior temperature of trailers to 71 degrees C for 30 min to promote drying
      and degradation of PRRSV. Trailer interiors were artificially contaminated with 5
      x 10(5) TCID50 of PRRSV strain MN 30-100, then treated with 1 of 4 treatments: 1)
      TADD; 2) air only (no supplemental heat); 3) overnight (8 h) drying; and 4)
      washing only. Following treatment, swabs were collected from the trailer
      interiors at 0, 10, 20, and 30 min post-treatment and from the overnight group
      after 8 h. Swabs were tested for PRRSV-RNA by polymerase chain reaction (PCR). As
      a measure of the presence of infectious PRRSV, sentinel pigs were housed in
      treated trailers for 2 h post-treatment and supernatants from swabs were injected
      IM into naive pigs (bioassay), the recipient pigs were then tested for PRRSV
      infection. All trailers were PRRSV positive by PCR immediately after washing,
      prior to treatment (pt). At 10 min pt, 7/10 swabs were positive from the TADD
      trailers; however, all swabs collected at 20 and 30 min pt were PRRSV negative by
      PCR, and trailer interiors were visibly dry. In contrast, 9/19, 6/10, and 6/10
      swabs collected at 10, 20, and 30 min, respectively, from trailers treated with
      air only were positive and visibly wet. All swabs (10/10) collected from trailers
      treated with washing only were PRRSV positive by PCR and all swabs collected at 8
      h of drying were PRRSV negative by PCR. All tests for the presence of infectious
      PRRSV were negative for trailers treated with TADD and overnight drying, while
      infectious PRRSV was detected in sentinel pigs and bioassay pigs in the other
      groups. Under the conditions of this study, the efficacy of the TADD system was
      equal to that of the overnight drying treatment, and it required a shorter period
      of time to complete its objective.

PMID- 15745223
TI  - Subcellular fractions of Brucella ovis distinctively induce the production of
      interleukin-2, interleukin-4, and interferon-gamma in mice.
AB  - The aim of this study was to evaluate the effect of 3 Brucella ovis subcellular
      protein fractions: Outer membrane (OMP), inner membrane (IMP), and cytoplasm
      (CP), on cellular immune response by in vitro production of interleukin (IL)-2,
      IL-4, and interferon (IFN)-gamma. Each fraction was inoculated 3 times into
      Balb/c mice, primary cultures of mice spleen cells were done, and these were then
      stimulated with the fractions. Culture supernatants were collected at 24, 48, 72,
      96, and 120 h postinoculation. Cytokine concentration was measured by Duoset
      enzyme-linked immunosorbent assay (ELISA). The OMP fraction induced highest
      cellular immune response of 1000 pg/mL of IL-2 at 24 h, which decreased to < 100
      pg/mL by 96 h. The IL-2 response for the IMP fraction was low at 24 h, but
      exceeded that of the OMP fraction at 72, 96, and 120 h. The CP showed a poor IL
      response. Regarding the IFN-gamma production, OMP and IMP induced a high response
      at 120 h. These results open the possibility for the use of B. ovis outer and
      inner membrane proteins as a subcellular vaccine.

PMID- 15745225
TI  - An evaluation of disinfectants for the sanitation of porcine reproductive and
      respiratory syndrome virus-contaminated transport vehicles at cold temperatures.
AB  - The objective of this study was to evaluate the efficacy of commercially
      available disinfectants to sanitize porcine reproductive and respiratory syndrome
      virus (PRRSV) contaminated trailer models in cold climates (-20 degrees C and 4
      degrees C). Disinfectants evaluated included Synergize, Aseptol 2000, Biophene,
      Sentramax, Virkon, Tek Trol, and DC&R. All products were applied to trailers via
      fumigation at 4 degrees C. Following experimental contamination of model trailers
      with PRRSV MN 30-100 (5 x 10(5) TCID50), models were tested for the presence or
      absence of PRRSV-RNA by polymerase chain reaction (PCR) on swabs collected 0, 30,
      and 60 min after treatment. Treatments included washing only, washing plus
      disinfectant fumigation, washing plus fumigation, and washing plus overnight
      drying. The PRRSV-RNA detected across trailers ranged from 0/12 replicates in
      trailers treated with Synergize or allowed to dry for 8 h. These trailers were
      also negative for the presence of infectious PRRSV, based on the lack of sentinel
      pig infection (0/4 replicates). In contrast, the detection of PRRSV-positive
      swabs by PCR ranged from 3/12 (Aseptol) to 10/12 (Biophene). Based on these
      results, the efficacy of Synergize was evaluated at -20 degrees C. In an attempt
      to reduce the impact of freezing on disinfectant activity, 30 mL of disinfectant
      was added to a 3840 mL of a 40% methanol solution, a 10% propylene glycol (PG)
      solution, or water alone. The PRRSV-contaminated trailers were treated with 1 of
      3 disinfectant mixtures via fumigation, stored for 8 h at -20 degrees C, allowed
      to thaw, and sampled as described. Trailers treated with 40% methanol or 10% PG
      did not freeze and were negative for PRRSV-RNA and infectious virus following
      thawing. In contrast, trailers treated with disinfectant and water were frozen
      within 60 min at -20 degrees C, and decontamination was not successful.

PMID- 15745226
TI  - Eradication of porcine reproductive and respiratory syndrome virus by serum
      inoculation of naive gilts.
AB  - The acclimatization program included exposure to serum and recovery. A continuous
      flow unit (nursery to finishing) from the same farm was selected as a potential
      source of porcine reproductive and respiratory syndrome virus (PRRSV). Negative
      gilts were inoculated 5 d after arrival by intramuscular injection of serum from
      selected animals. There was a significant reduction in seroprevalence in the sow
      herd 1 y after implementation of the gilt inoculation program (P < 0.05). At that
      time, all of the tested nursery pigs were negative for PRRSV. The fully
      segregated finisher population had a significant reduction in the frequency of
      PRRSV positive animals (P < 0.05) by enzyme-linked immunosorbent assay (ELISA),
      with all animals testing negative by the end of the study. However a persistent
      seroconversion was observed in the partially segregated finisher pigs (P > 0.05).
      In conclusion, the gilt serum inoculation program achieved sow herd
      stabilization, as defined by the production of negative weaned pigs and this
      resulted in the eradication of PRRSV in the fully segregated flow.

PMID- 15745227
TI  - Biocompatibility of microparticles into soft tissue fillers.
AB  - The increasing need for long-lasting injectable soft tissue fillers for the
      treatment of wrinkles and folds requires a critical discussion of the
      biocompatibility on a scientific background. Since biological fillers made of
      collagen and hyaluronic acid will be resorbed over time, copolymer biomaterials
      with microparticles have been developed in recent years. The microparticles
      followed special and essential demands because of the interaction with the
      tissue. In search of an ideal soft tissue filler substance, a variety of
      biomaterials with microparticles suspended have been created for injecting into
      dermal defects, into the urethra of patients with urinary incontinence, and in
      patients with vocal cord insufficiency. The particles differ in chemical
      composition, surface structure, surface charge, and particle size and evoke
      different host reactions, accordingly.

PMID- 15745228
TI  - Hyaluronic acid and its use as a "rejuvenation" agent in cosmetic dermatology.
AB  - Since 1996, hyaluronic acid (HA) has been launched onto the market in Europe.
      Since then, different companies proposed their HAs. Biomatrix (NJ, USA) proposes
      an animal-derived HA (from rooster comb). Q-Med AB (Uppsala, Sweden) and LEA-DERM
      (Paris, France) are the main companies to have a nonanimal HA. HA is produced by
      bacterial fermentation from a specific strain of streptococci. HA has no species
      specificity and theoretically has no risk of allergy. No skin testing is
      necessary before injecting because HA is a biodegradable agent. To be utilized as
      a filler agent for improving wrinkles, scars, or increasing volumes, HA must be
      stabilized to obtain a sufficient half-life. Process of stabilization varies,
      according to each manufacturer. This explains the differences in longevity and in
      viscosity of the different products. Several HAs are suitable to fine lines, to
      deep wrinkles/folds, or to increase volume. A new indication for "rejuvenation"
      is injection into the superficial dermis and epidermis. The HA (stabilized or
      not) is not used to fill in but rather to hydrate and finally to rejuvenate the
      skin. This procedure must be repeated at intervals of a few weeks or months. If
      HA is the safest filler agent in cosmetic indications today, some rare side
      effects may appear and must be known to inform patients. Most of these
      complications are not severe and will disappear when the product is degraded.

PMID- 15745229
TI  - The use of poly-L-lactic acid in the management of soft-tissue augmentation: a
      five-year experience.
AB  - Poly-L-lactic acid (PLA) New-Fill* is one of the latest implants commercialized
      among bioresorbable fillers. This synthetic polymer is biocompatible,
      biodegradable, immunologically inert, and free from toxicity. All these necessary
      properties provide theoretical safety. New-Fill* has to be injected deeply into
      the dermis or into the subcutaneous tissue, so the main indications of New-Fill*
      are the correction of important wrinkles and furrows from face (Nasolabial folds,
      "Marionette" lines), and especially spread tissue augmentation for "face
      modeling" as for cheeks lipoatrophies in HIV patients receiving an antiprotease
      treatment. After two or three sessions, results are appreciable and equivalent to
      other resorbable fillers, but seem to last longer. On the other hand, the cost of
      this material is widely cheaper than others. However, we do not lose sight that
      the practitioner fee related to a series of two to three sessions of injections
      compensates for this material economy. Superficial injections should be avoided.
      They may increase the risk of persistent granulomas, which will be difficult to
      manage. Even if severe complications are rare, they must be revealed to the
      patient to obtain his informed consent before injecting.

PMID- 15745230
TI  - Polymethyl methacrylate microspheres in collagen.
AB  - Artecoll was developed about 20 years ago and underwent a number of production
      changes until it recently became FDA approved under the new name of Artefill.
      This product contains 20% polymethyl methacrylate (PMMA) microspheres with a
      diameter of 30 to 40 microm, which are suspended in a 3.5% atelo-collagen
      solution. The PMMA microspheres are now purified and no longer have an
      electrostatic charge, which in part was the cause for the early granulomatous
      reactions. Further, PMMA has long been known as bone cement and has been used in
      cosmetic surgery with a very good safety record. PMMA microspheres are
      biologically inert and nondegradable. The treatment results are therefore
      permanent and technical errors as well as incorrect injections will last. Due to
      the early record of granuloma formation, there is still a debate as to whether
      this product-as well as all other permanent fillers-should be injected for
      cosmetic reasons or not. With proper indications, excellent injection techniques,
      and realistic expectations as to what can be expected, this product has now
      proved to be one of the superior permanent filler substances.

PMID- 15745231
TI  - Polyacrylamide gel in cosmetic procedures: experience with Aquamid.
AB  - Polyacrylamides have been used in tissue augmentation since 1980. AQUAMID
      injections amounting to 40,000 have been done for facial and body corrections in
      cosmetic and reconstructive medicine and surgery. Possible neurotoxic and
      carcinologic effects of acrylamide and their stability are reported. The most
      important complications are infection, granuloma, and migration. All actual
      studies and results are reported. Main indications are lips, nasolabial fold, and
      malar area.

PMID- 15745232
TI  - The polyalkylimide gel: experience with Bio-Alcamid.
AB  - Bio-Alcamid is a new nonbiodegradable substance which is easy to use and which
      allows one to create volume on both the body and the face. This substance is
      extractable even after several years. This allows more patients to use a
      nonbiodegradable substance for esthetic problems of lipoatrophy treatment or for
      posttraumatic or therapeutic atrophy of subcutaneous tissue.

PMID- 15745233
TI  - The histological aspects of fillers complications.
AB  - The histological aspects of resorbable heterologous fillers (bovine collagen,
      acid hyaluronique), autologous fillers (lipofilling, dermis-fat graft),
      biodegradable fillers (New-Fill), and permanent fillers (silicone, Artecoll,
      Evolution, Aquamid, DermaLive, DermaDeep, Bioplastique, Paraffin) are described.
      This article relates the morphological aspect of these materials, the normal
      tissue reaction after injection, and its chronological evolution as the
      morphological aspects from the different side effects, more frequently observed
      for the permanent fillers. They mainly consist of granulomatous reactions which
      may appear long after injection.

PMID- 15745234
TI  - Is your early warning system working?

PMID- 15745235
TI  - Profile. Robert H. Howland, MD.

PMID- 15745236
TI  - Therapeutic brain stimulation for mental disorders.

PMID- 15745237
TI  - Community drug abuse prevention in a Hmong village in Thailand.
AB  - The goal of this project was to implement a model of drug abuse prevention,
      drawing on health care, psychosocial and legal principles, in a selected village
      community in Thailand. Primary, secondary, and tertiary prevention strategies
      were used within a nursing conceptual framework that included the interactions
      among the person, drugs, and environment. An initial community survey revealed
      112 addicted individuals and identified many atrisk groups, such as children of
      addicted parents, adolescents, and women. Primary health care and dental health
      services were provided in the community, as well as drug abuse education and
      activities for school children and at-risk groups. Treatment camps were also
      established in the community on two occasions to provide detoxification and
      rehabilitation services for addicted individuals. At the end of the 3-year
      program, there were no new addicted individuals, and the number of addicted
      individuals decreased from 112 to 50 (after first treatment) and 26 (after second
      treatment). In addition, the villagers were more aware of problems related to
      using opium and heroin and of modern, approved drugs to treat illnesses. The
      prevention strategies were beneficial for the community members, as well as the
      addicted individuals and theirfamilies.

PMID- 15745238
TI  - Seclusion & restraint: a historical perspective.
AB  - (1) The use of restraints in the care of psychiatric patients has been a topic of
      ethical controversy since the beginning of psychiatric medicine. (2)
      Enlightenment physicians regarded psychiatric illness as the loss of reason, and
      many advocated the use of restraints to help violent patients regain the use of
      reason. (3) John Conolly, a British alienist (a term used for psychiatrists) of
      the mid 1800s, claimed it was possible to treat psychiatric patients without the
      use of mechanical restraints, but he made liberal use of seclusion and physical
      restraint by attendants to manage violent behavior. (4) American alienists
      expressed misgivings about the use of mechanical and chemical restraint but most
      were reluctant to relinquish any usable intervention.

PMID- 15745239
TI  - Social support among homeless and housed mothers: an integrative review.
AB  - Homelessness has been associated with levels of stress beyond the normal strain
      of living in poverty. For mothers who are homeless, support from their social
      networks may provide a buffer from some of the stresses associated with being
      homeless. To better understand the relationship between social support and female
      headed homeless families, an integrative review was conducted of 12 research
      articles that compare social support among low-income housed mothers and homeless
      mothers, using guidelines set forth by Ganong. The included studies revealed four
      significant attributes of social support among housed and homeless mothers: size
      of the social support network; composition of the social support network;
      contacts with members of the social support network; and perceived support from
      members of the social support network. Nurses who work with homeless families are
      in a position to help develop ways for these families to cultivate and maintain
      their social support networks while homeless. Nurses can be available to offer
      support, including the necessary mental health services or referrals.

PMID- 15745240
TI  - The first ring of eternity.

PMID- 15745241
TI  - Potential oxidative stress in the bodies of electric arc welding operators:
      effect of photochemical smog.
AB  - OBJECTIVE: To investigate whether photochemical smog emitted during the process
      of electric arc welding might cause oxidative stress and potential oxidative
      damage in the bodies of welding operators. METHODS: Seventy electric arc welding
      operators (WOs) and 70 healthy volunteers (HVs) were enrolled in a randomized
      controlled study design, in which the levels of vitamin C (VC) and vitamin E (VE)
      in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT)
      and glutathione peroxidase (GPX), and the level of lipoperoxide (LPO) in
      erythrocytes were determined by spectrophotometry. RESULTS: Compared with the
      average values of the above experimental parameters in the HVs group, the average
      values of VC and VE in plasma as well as those of SOD, CAT and GPX in
      erythrocytes in the WOs group were significantly decreased (P < 0.005-0.0001),
      while the average value of LPO in erythrocytes in the WOs group was significantly
      increased (P < 0.0001). The findings from the partial correlation analysis on the
      controlling of age suggested that with a prolonged duration of exposure to
      photochemical smog the values of VC, VE, SOD, and GPX, except for CAT, in the WOs
      were decreased gradually (P < 0.05-0.005), the value of LPO in the WOs was
      increased gradually (P < 0.001), and that with the ozone dose increased in the
      air in each worksite VC, VE, SOD, CAT and GPX decreased (P < 0.005-0.001), but
      LPO increased (P < 0.001). The findings from the reliability analysis for the VC,
      VE, SOD, CAT, GPX, and LPO values which were used to reflect oxidative stress and
      potential oxidative damage in the WOs showed that the reliability coefficients'
      alpha (6 items) was 0.8021, P < 0.0001, and that the standardized item alpha was
      0.9577, P < 0.0001. CONCLUSION: Findings in the present study suggest that there
      exists an oxidative stress induced by long-term exposure to photochemical smog in
      the bodies of WOs, thereby causing potential oxidative and lipoperoxidative
      damages in their bodies.

PMID- 15745242
TI  - Enhancement of urinary elimination of 3-bromobenzanthrone metabolites by oral
      supplementation of ascorbic acid in guinea pigs.
AB  - OBJECTIVE: 3-Bromobenzanthrone (3-BBA), an anthraquinone intermediate dye, is
      extensively used in textile industry. Since, our prior studies have shown that 3
      BBA caused significant depletion of ascorbic acid (AsA) levels, the effect of
      exogenous supplementation of AsA on the urinary elimination of 3-BBA metabolites
      was investigated. METHOD: Guinea pigs were treated with single oral dose of 3-BBA
      (50 mg/kg b. wt.) in groundnut oil while another group was treated with single
      oral dose of 3-BBA (50 mg/kg b. wt.) along with 3 day prior and post oral
      supplementation of AsA. Control groups were either treated with groundnut oil or
      AsA alone. Urine from individual animals was collected, extracted and analysed on
      HPTLC. RESULTS: The highest elimination of 3-BBA (75 microg) was found to be in 0
      24 h urine fraction which decreased to 18 microg and 5 microg in the two
      subsequent 24 hourly fractions of urine. Exogenous supplementation of AsA
      increased the total urinary elimination of 3-BBA by almost 77%. A total of 10
      fluorescent metabolites excluding the parent compound were eliminated in the
      urine of guinea pigs treated with 3-BBA. Densitometric scanning of chromatogram
      showed different peaks at Rf 0.18, 0.22, 0.27, 0.34, 0.40, 0.48, 0.56, 0.66,
      0.72, 0.80, and 0.95 which were eliminated and marked as urinary metabolite 1, 2,
      3, 4, 5, 6, 7, 8, 9, 10, and 11 respectively. AsA not only significantly enhanced
      the elimination of 3-BBA metabolites but also modified the pattern of metabolites
      drastically in 0-6 h, 6-24 h and 24-48 h urine fractions. CONCLUSION: These
      results indicate that AsA may be useful in protecting the toxicity of 3-BBA by
      fascilitating the urinary metabolite(s) excretion of 3-BBA.

PMID- 15745243
TI  - Comparative study on schizontocidal activity of recrystallized or crude daphnetin
      against malaria parasites.
AB  - OBJECTIVE: To compare the schizontocidal activity of recrystallized or crude
      daphnetin against malaria parasites in vivo. METHODS: Schizontocidal activity of
      recrystallized or crude daphnetin at various dosages was assessed in mice
      infected with Plasmodium berghei ANKA using a "4-day suppress assay". RESULTS:
      The comparison of the reduction rate of parasitemia caused by either
      recrystallized or crude dephnetin showed that ED(50) of crude daphnetin was 18.36
      mg/kg, with 95% confidence limit of 5.96-56.54 mg/kg while ED50 of recrystallized
      daphnetin was 11.46 mg/kg, with 95% confidence limit of 8.63-15.22 mg/kg.
      CONCLUSION: The results indicate that the efficacy of recrystallized daphnetin is
      37.6% higher than that of crude daphnetin.

PMID- 15745244
TI  - Scavenging action of zinc and green tea polyphenol on cisplatin and nickel
      induced nitric oxide generation and lipid peroxidation in rats.
AB  - OBJECTIVE: Toxic metal ions have been implicated in the generation of reactive
      oxygen species (ROS) and nitric oxide (NO). Metallothionines (MT) and plant
      flavonoids have been reported in the intervention against oxidative damage. We
      investigated the effect of zinc induced MT and green tea polyphenol (GTP) in
      reducing the oxidative responses induced by nickel and platinum. METHODS: Zinc
      (10 mg/kg b. wt, sc) was administered to rats twice at a gap of 24 hrs and GTP
      (10 mg/100 mL in drinking water) was fed ad libitum for 8 days. Nickel chloride
      (150 umol/kgb.wt, ip) and cisplatin (50 mumol/kg b.wt, sc) was administered to
      rats 24 h after Zn or GTP pre-treatment. Animals of all the groups were
      sacrificed 16 hrs after treatment and biochemical markers for toxicity were
      monitored. RESULTS: Zinc or GTP pre-treatment caused significant protection
      against nickel or cisplatin enhanced mortality in rats, and reduction in lipid
      peroxidation and NO. CONCLUSION: It is proposed that inhibition of ROS and NO by
      GTP and zinc may prove useful as a selective pharmacological agent in the
      amelioration of metal toxicity.

PMID- 15745245
TI  - HIV/AIDS-related discrimination in Shanxi rural areas of China.
AB  - OBJECTIVE: In order to explore the features of discrimination against people with
      HIV/AIDS in rural areas, a community-based intervention was carried out in two
      pilot communities of X County of Shanxi Province from September 2002 to October
      2003. METHODS: Data were collected using qualitative methods (in-depth interview
      and focus group discussion) and anonymously structured questionnaires. RESULTS:
      (1) Severe discrimination against people infected with HIV/AIDS was revealed in
      the target communities. However, the response to HIV/AIDS was different in each
      community. (2) People were reluctant to disclose their HIV status or get tested
      for HIV, which endangered their sexual partners to contract HIV through
      unprotected sexual intercourses. (3) Attitudes towards people infected with
      HIV/AIDS varied. (4) Public education promoted a better understanding of HIV/AIDS
      which in turn improved community attitudes and behaviors towards people with
      HIV/AIDS. CONCLUSION: HIV/AIDS-related discrimination undermines both
      individuals' and communities' responses to HIV/AIDS and may be a serious obstacle
      towards effective HIV/AIDS prevention and control.

PMID- 15745246
TI  - Polymorphisms of exon 17 of insulin-receptor gene in pathogenesis of human
      disorders with insulin resistance.
AB  - OBJECTIVE: To investigate the relationship between polymorphisms of insulin
      receptor (INSR) gene and insulin resistance in a population-based study in China.
      METHODS: Polymerase Chain Reaction (PCR) was used to the amplify Exon 17 of INSR
      gene and all amplified products were analyzed by direct sequencing. RESULTS: Six
      single-nucleotide polymorphisms (SNPs) were found at the following loci: T to TC
      at the locus of 10699 (Tyr(984)), G to GC at the locus of 10731 (Glu(994)),
      Deletion G at the locus of 10798 (Asp(1017)), C to T/TC at the locus of 10923
      (His(1058)), C to CA at the locus of 10954 (Leu(1069)), and T to TA at the locus
      of 10961 (Phe(1071)), which might not change the amino acid sequence. The data
      were in agreement with the test of Hardy-Weinberg balance (P > 0.05). Among the
      345 cases, all clinical indices were higher in males than in females except for
      HDL cholesterol (P < 0.05). The proportion of insulin resistance in males (64.4%)
      was higher than that in females (35.6%, OR = 1.83). It implied that the relative
      risk of developing insulin resistance in males was 1.83 times as high as that in
      females. The biochemical indices in different loci on Exon 17 showed that the
      individuals with deletion G on the locus of 10798 had lower TG (P = 0.052) and
      higher HDL (P = 0.027) than those without deletion G on the same site. Homa-Index
      was lower in those with deletion G than in those without deletion G (P > 0.05).
      After sex stratification in analysis, all allele frequencies on the six loci of
      SNPs of Exon 17 had different distributions between the insulin resistant group
      and the control group, but P > 0.05. CONCLUSION: SNPs of Exon 17 of INSR gene are
      unlikely to play a direct role in the pathogenesis of human disorders with
      insulin resistance.

PMID- 15745247
TI  - Cu, Mn, Fe, and Zn levels in soils of Shika area, Nigeria.
AB  - OBJECTIVE: Heavy metals presented in toxic amounts can become injurious to human
      health. In areas where there is a high level of human activities on soils (such
      as agriculture and grazing) studies are therefore required from time to time to
      monitor levels of such metals in the soils in order to identify the point in time
      when toxicity problems become real. The objective of this paper is to determine
      the concentrations of some trace metals (Cu, Mn, Fe, and Zn) in soils under
      cultivation and grazing practices in Shika, a rural area of Kaduna state of
      Nigeria. METHOD: In this study, soil samples collected from three different
      categories of locations (cultivated, grazed, and uncultivated/non-grazed serving
      as a control) across Shika area, Nigeria, were analysed for some trace metal
      levels (Cu, Mn, Fe, and Zn) using atomic absorption spectrophotometry. For each
      category, multiple sites were chosen to accommodate all possible intra-category
      variations, especially in terms of land use and management history and
      topographic characteristics. Topsoil (0-15 cm) and subsoil (20-30 cm) samples
      were collected from every site and analysed for the above metals. Averaged values
      of the metals for the three categories revealed that Zn is the most abundant
      metal, followed by Fe, then Mn and Cu the least. RESULTS: The results obtained
      indicate that the cultivation practices, and to a lesser extent grazing, in the
      area result in higher levels of all the metals than in the control, suggesting
      that crop immobilization of the metals from soils of the area is low, and that
      their systematic accumulation is taking place in cultivated soils of the area.
      Prospects of having elevated soil levels of the metals due to cultivation
      practices in the area therefore seem quite high. CONCLUSION: On the basis of the
      results obtained, it was concluded that grazing and cultivation practices have in
      general caused some significant elevations in the bioavailable (i.e the plant
      available forms) levels of Zn, Fe, Mn, and Cu in soils of the area.

PMID- 15745248
TI  - Genes differentially expressed in human lung fibroblast cells transformed by
      glycidyl methacrylate.
AB  - OBJECTIVE: To define the differences in gene expression patterns between glycidyl
      methacrylate (GMA)-transformed human lung fibroblast cells (2BS cells) and
      controls. METHODS: The mRNA differential display polymerase chain reaction (DD
      PCR) technique was used. cDNAs were synthesized by reverse transcription and
      amplified by PCR using 30 primer combinations. After being screened by dot blot
      analysis, differentially expressed cDNAs were cloned, sequenced and confirmed by
      Northern blot analysis. RESULTS: Eighteen differentially expressed cDNAs were
      cloned and sequenced, of which 17 were highly homologous to known genes (homology
      = 89%-100%) and one was an unknown gene. Northern blot analysis confirmed that
      eight genes encoding human zinc finger protein 217 (ZNF217), mixed-lineage kinase
      3 (MLK-3), ribosomal protein (RP) L15, RPL41, RPS 16, TBX3, stanniocalcin 2
      (STC2) and mouse ubiquitin conjugating enzyme (UBC), respectively, were up
      regulated, and three genes including human transforming growth factor beta
      inducible gene (Betaig-h3), alpha-1,2-mannosidase 1A2 (MAN 1A2) gene and an
      unknown gene were down-regulated in the GMA-transformed cells. CONCLUSION:
      Analysis of the potential function of these genes suggest that they may be
      possibly linked to a variety of cellular processes such as transcription, signal
      transduction, protein synthesis and growth, and that their differential
      expression could contribute to the GMA-induced neoplastic transformation.

PMID- 15745249
TI  - Changes of expressions of VEGF, bFGF, and angiogenesis, and effect of benazepril,
      bFGF on angiogenesis in acute myocardial infarction model of the rabbits.
AB  - OBJECTIVE: To explore the changes of vascular endothelial growth factor (VEGF),
      basic fibroblast growth factor (bFGF) and angiogenesis, and the effects of bFGF,
      angiotensin converting enzyme inhibiter(ACEI) benazepril on the angiogenesis in
      acute myocardial infarction (AMI) model of rabbits, and to provide a probable
      evidence for the treatment of AMI. METHODS: AMI model was established by ligating
      anterior descending branch of coronary artery of Japan-Sino hybridization white
      rabbits. The postoperative rabbits were randomly divided into 6 groups and each
      group was treated with different drugs. Groups 1 and 2 were treated with normal
      saline (NS) for 28 and 14 days (d), group 3 and 4 with bFGF for 28 and 14 d,
      groups 5 with benazepril for 14 d, and group 6 with benazepril and bFGF for 14 d
      respectively. The rabbits were killed on the 14th or 28th d and their hearts were
      excised, sectioned and stained with HE, Masson trichrome to observe VEGF, bFGF
      and CD(34) under a microscope, which were quantified with a computer-assisted
      morphometry. RESULTS: Compared with group 1, the granulation tissue of infarction
      zone (IZ) in group 2 freshened up, and the capillary density (CD) in IZ was
      increased (P = 0.002). The CD in the IZ as well as VEGF and bFGF in groups 3 and
      4 were increased respectively (P = 0.011-0.037). In group 5 the changes of VEGF
      and bFGF were not found in the IZ and the border zone (BZ) while CD was
      significantly increased (35.4% and 25.6%, P = 0.036 and 0.037). Compared with
      group 2, the CD in the IZ and BZ of group 6 was significantly increased (63.4%
      and 44.3% P = 0.007 and 0.007), meanwhile VEGF and bFGF were increased. Compared
      with group 5, only VEGF was increased. CONCLUSION: Intravenous bFGF may increase
      VEGF and bFGF significantly, thus promoting the angiogenesis in the IZ and BZ in
      cardiac infarction as VEGF and bFGF are the potent angiogenic growth factors.
      Benazepril may promote angiogenesis in the IZ and BZ in cardiac infarction, but
      its mechanism is irrelative to the expression of VEGF and bFGF. The combination
      of benazepril and bFGF may promote, to some extent, the expression of VEGF and
      bFGF, but their effect on angiogenesis has not been found.

PMID- 15745250
TI  - Monitoring of pollution of air fine particles (PM2.5) and study on their genetic
      toxicity.
AB  - OBJECTIVE: To compare PM2.5 pollation level between the city of coal-fuel
      pollution (Taiyuan) and the city of pollution mixed with coal fuels and vehicle
      exhausts (Beijing), to analyze the concentration of B[a]p and Pb in the
      pollutants, and to study the DNA damage by PM2.5. METHODS: Air fine particles
      (PM2.5) were collected in Beijing and Taiyuan by means of the filter membrane
      method, the concentration of B[a]p and Pb were analyzed by high performance
      liquid chromatography and atomic absorption spectroscopy respectveily, and the
      damage of DNA by PM2.5 was detected by single cell gel-electrophoresis (SCGE)
      using the human lung epithelial cells (A549) as target cells. RESULTS: The
      concentration of PM2.5 in the winter of Beijing was 0.028-0.436 mg/m(3), and that
      in Taiyuan was 0.132-0.681 mg/m(3). The concentration of B[a]p was 0.104 and
      0.156 microg/mg on PM2.5 of Beijing and Taiyuan, respectively, whereas the
      concentration of Pb was 1.094 and 1.137 microg/mg on PM2.5 of Beijing and
      Taiyuan, respectively. Exposure to PM2.5 at the concentrations of 5, 50, and 200
      microg/mL for 12 h and 24 h caused DNA damage of the human alveolar epithelium,
      and the ratios of the tailing and length of the tail were all significantly
      different from those of the negative control group (P < 0.05), and indicated a
      dose-response relationship. CONCLUSION: PM2.5 has certain genetic toxicity.

PMID- 15745251
TI  - Cohort studies on cancer mortality among workers exposed only to chrysotile
      asbestos: a meta-analysis.
AB  - OBJECTIVE: To determine whether there was excessive risk of cancer among workers
      exposed to chrysotile fiber alone by applying a meta-analysis technique. METHODS:
      All data meeting the criteria of cohort studies on cancer mortality among workers
      exposed only to chrysotile were incorporated into meta-analysis. Pooled
      standardized mortality ratios (SMRs) and their corresponding 95% confidence
      intervals (CIs) for main cancer sites were calculated using two approaches of
      unweighted ratio and random effect model. The heterogeneity and its sources of
      the results were examined with a Q-statistic and Z-score test. The dose-response
      effect as reflected in the percentage of all deaths due to mesothelioma served as
      a proxy measure of chrysotile exposure. RESULTS: A cohort of twenty six workers
      exposed to chrysotile alone was summarized. The significantly elevated meta-SMRs
      for all deaths (1.27), all cancers (1.28), cancers of respiratory organs (2.51),
      cancers of lung (2.35) and cancers of stomach (1.24) were observed. The
      significantly elevated meta-SMRs for lung cancer within occupational strata were
      observed among textile workers (3.55), asbestos product manufacturers (3.30),
      miners and millers (2.24), cement product workers (1.22), and for stomach cancer
      among asbestos product manufacturers (1.49). Meta-SMRs for cancers at other sites
      were not significant. Meta-SMR for lung cancer showed an increasing trend with an
      elevated percentage of all deaths from mesothelioma, but no such trend for
      stomach cancer. CONCLUSION: There are excessive risks of lung cancer and
      mesothelioma among workers exposed to chrysotile fiber alone, and likely no
      convincing indication of an etiological association between chrysotile exposure
      and cancers at other sites.

PMID- 15745252
TI  - Antimutagenicity of propolis against some mutagens in vivo and in vitro.
AB  - OBJECTIVE: To evaluate the antimutagenicity of propolis in vivo and in vitro.
      METHODS: Salmonella typhimurium strains TA98 and TA100 were used as a test model
      in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without
      S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice
      testicle cell were applied as a test model in vivo against two mutagens CP and
      MMC. RESULTS: The present study clearly demonstrated that propolis could inhibit
      mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and
      significant antimutagenic effects (P < 0.05) were obtained in TA98 strain at 2000
      and 3000 microg/plate. It also could inhibit mutagenicity of both DMC and 2AF to
      TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P
      < 0.05) appeared at 1000, 2000, and 3000 microg/plate. The results of
      antimutagenicity test in vivo revealed that propolis could inhibit MN formation
      significantly (P < 0.05) at the doses of 45.0 and 135.0 mg/kg b. w., and decrease
      the frequency of chromosome aberrants and chromosome aberrant cells significantly
      (P < 0.05) only at the dose of 135.0 mg/kg b. w. CONCLUSION: The propolis is a
      good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC
      in vivo.

PMID- 15745253
TI  - Intrauterine infections and birth defects.
AB  - Intrauterine infection is an important cause of some birth defects worldwide. The
      most common pathogens include rubella virus, cytomegaloviurs, ureaplasma
      urealyticum, toxoplasma, etc. General information about these pathogens in
      epidemiology, consequence of birth defects, and the possible mechanisms in the
      progress of birth defects, and the interventions to prevent or treat these
      pathogens' infections are described. The infections caused by rubella virus,
      cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. are common, yet they
      are proved to be fatal during the pregnant period, especially during the first
      trimester. These infections may cause sterility, abortion, stillbirth, low birth
      weight, and affect multiple organs that may induce loss of hearing and vision,
      even fetal deformity and the long-term effects. These pathogens' infections may
      influence the microenvironment of placenta, including levels of enzymes and
      cytokines, and affect chondriosome that may induce the progress of birth defect.
      Early diagnosis of infections during pregnancy should be strengthened. There are
      still many things to be settled, such as the molecular mechanisms of birth
      defects, the effective vaccines to certain pathogens. Birth defect researches in
      terms of etiology and the development of applicable and sensitive pathogen
      detection technology and methods are imperative.

PMID- 15745255
TI  - Boxing is a dangerous and brutal sport.

PMID- 15745254
TI  - Study and application of herbal disinfectants in China.
AB  - Disinfection means killing or removing pathogenic microorganisms in media to
      realize a harmless process. A disinfectant, which is also referred to as a
      disinfection medicine in relevant regulations, is the medicine used to kill
      microorganisms for the purpose of disinfection. The disinfectants prepared from
      plants (including traditional Chinese herbal medicines) and the extracts thereof
      are called herbal disinfectants. China has a long history of using herbal
      disinfectants. As early as in 533 A.D., the use of Cornel to sterilize well water
      was recorded in Necessary Techniques for Qi People by Jia Enxie of the Beiwei
      Dynasty. During the Dragon Boat Festival, people often use fumigants made of
      traditional Chinese herbal medicines like Chinese Atractylodes, Argy Wormwood
      Leaf and Red Arsenic Sulfide to smoke their houses, so as to ward off plagues and
      drive away evils. In fact this is now a kind of disinfection practice.

PMID- 15745256
TI  - Regional Rehabilitation Unit (RRU) Portsmouth.

PMID- 15745257
TI  - Improving the selection of candidates for Royal Marine recruit training by the
      use of a combination of performance tests.
AB  - Candidates who wish to undertake Royal Marine recruit training, a physically
      strenuous course which now extends 32 weeks, must first of all successfully
      complete a Personal Qualities Assessment (PQA) and four psychomotor tests (Naval
      Recruiting Tests or RTs) before attending a three-day selection course at the
      Commando Training Centre, Lympstone, where their physical capabilities are tested
      to the full. The effectiveness of these procedures was untested until the
      Institute of Naval Medicine conducted a retrospective study during 1999-2000 from
      which the present study is taken. Data from 1232 recruits were examined to
      explore the relationship between the outcome of Commando training (pass or fail)
      with these various selection measures. Estimated aerobic power, time to complete
      the assault course and age were associated with outcome, as were PQA, RTs 1, 3, 4
      and total RT score. A regression equation comprising aerobic fitness, assault
      course time, RT4 and age gave the best overall prediction of outcome (64%). It is
      suggested that this mathematical approach provides a scientifically valid and
      objective assessment tool for future selection strategies.

PMID- 15745258
TI  - Association between anatomical features and anterior knee pain in a "fit" service
      population.
AB  - Anterior knee pain and overuse sports type injuries have been associated with
      anatomical factors. Specific diagnosis in knee pain is difficult, most service
      patients are grouped together as "Patello-Femoral Stress Syndrome". Knee pain
      incidence within the service population is unknown, but thought to be greater
      than those presenting to General Practitioners. 293 active duty service men (100
      Army and 193 Royal Navy) were interviewed and examined in relation to their
      knees. 138 measurements were made on each subject. 118 admitted to knee problems.
      Six had specific diagnoses, ranging from patellar tendonitis to ACL deficiency
      (with marked anterior instability). The remaining 112 individuals formed the
      study group and examination findings were compared with the 175 without Patello
      Femoral Stress Syndrome. The results have been analysed to determine normal
      ranges and predictors of knee pain. Age, years in the military and results of
      patello-femoral compression tests were consistently significantly different
      between the groups. This survey provides useful information on normal values at
      examination. Q angle measurement was a poor predictor of knee pain. There was no
      clinically detectable anatomical variant that correlated with the Patello-Femoral
      Stress Syndrome. There was poor correlation between Tegner activity score and the
      perceived limitation on sport or work, as assessed on a visual analogue scale.

PMID- 15745259
TI  - The pathophysiology of exertional heatstroke.
AB  - Exertional heat illness remains a major cause of morbidity and occasional
      mortality within the Armed Forces. This review explores the normal responses to
      heat, known causes of exertional heatstroke, and suggests possible answers to the
      question of why one member of a military unit collapses with heat stroke, while
      matched controls at his side remain unaffected.

PMID- 15745260
TI  - Displaced distal fractures of the radius and ulna in children: the incidence of
      re-displacement in plaster.

PMID- 15745261
TI  - Graduated compression stockings reduce the venous velocity augmentation of foot
      pumps.
AB  - The use of the A-V Impulse System of foot pumps and graduated compression
      stockings to reduce the incidence of thrombo-embolic disease after total hip
      arthroplasty is well recognised. It is not known if they have a synergistic
      effect as all clinical trials have used them in combination. We examined the
      effect compression stockings had on the ability of the A-V Impulse System to
      accelerate peak venous velocities in the common femoral vein in ten healthy
      volunteers using a duplex scanner. The use of foot pumps without stockings
      produced the greatest increase in peak venous velocity and this was 34% greater
      than using a foot pump with stockings. It is not known if this difference could
      account for a reduction in thrombo-embolic episodes and so we propose a
      randomised clinical trial.

PMID- 15745262
TI  - Helping to care for burn cases in WW2.

PMID- 15745264
TI  - Exercise Bersama Lima 2004--a combined joint approach.

PMID- 15745263
TI  - The changing world of military health care.

PMID- 15745265
TI  - Remembrance Sunday in Tangier.

PMID- 15745266
TI  - I'm a Medic get me out of here!!

PMID- 15745267
TI  - Fingerprint evidence in England and Wales--the revised standard.
AB  - Evidence of personal identity, often based solely on the comparison of a single
      finger impression, or fragment of an impression, has been accepted by courts of
      law at all levels in England and Wales since 1901, when the fingerprint system of
      identification was first adopted by police forces. Fingerprint identification is
      used by police forces world-wide, not only for the identification of latent
      fingermarks left at crime scenes, but also as the basis for ensuring accuracy in
      the criminal record system. For more than a century fingerprint evidence has been
      shown without doubt to be the best form of personal identification yet devised
      and millions of comparisons and subsequent identifications have been effected
      world-wide without any flaw in the system having been detected. From 1953-2001 it
      was the usual practice in England and Wales for the police to proffer fingerprint
      evidence showing 16 common matching characteristics, or features in agreement,
      between the two impressions being compared. In 1996 the Association of Chief
      Police Officers (ACPO) commissioned a review of the existing methods of
      presenting fingerprint evidence before the courts and on 11 June 2001 a new
      standard of fingerprint evidence was adopted by the police forces of England and
      Wales. This paper describes how the new standard was developed and implemented
      and why it was considered necessary to move away from the existing 16-point
      standard.

PMID- 15745268
TI  - An analysis of aftercare under section 117 of the Mental Health Act 1983.

PMID- 15745269
TI  - Cloning controversies: an overview of the science, ethics and politics.
AB  - Man's quest for knowledge is boundless. It is because of this quest and his
      untiring efforts to acquire it, that we have made such tremendous breakthroughs
      in the fields of science and medicine. Vaccines for hitherto incurable diseases,
      genetic engineering, and the correction of congenital and hereditary diseases are
      a few of these. With the successful cloning of 'Dolly', 'Molly' and 'Polly' we
      are now standing at the threshold of another major breakthrough--human cloning.
      However, are we ethically, morally and politically mature enough to 'go all the
      way' in a purely scientific manner, for the benefit of the human kind? A review
      of the scientific, ethical and political events in this field may be pertinent in
      trying to answer this important question.

PMID- 15745270
TI  - Self-inflicted burns fatalities in Manipal, India.
AB  - Death due to burns is an important public health problem. Suicide by burning is
      uncommon in the Western world compared with Asian countries. This study presents
      retrospective research carried out in the tertiary care teaching hospital of
      Kasturba Medical College, Manipal, Southern India, between January 1993 to
      December 2003 (11 years). Out of a total of 343 burns deaths during the above
      mentioned period, 39 were victims of suicide. The majority of deaths (46.1%)
      occurred in the 21-30 years age group, with a preponderance of the female sex
      (79.5%). Most of the victims belonged to the Hindu religion and the incident
      occurred mostly during the daytime. In the overwhelming majority of cases, the
      incident occurred at home (97.4%). In all cases kerosene was the accelerant and
      flame was the causative agent. In more than fifty per cent of cases, the total
      body surface area (TBSA) involved was more than 80%. Dowry demands and harassment
      were the reasons for committng suicide in 12 cases. More stringent laws and
      empowering female independence, both mentally and economically, will reduce
      suicidal burns in young women.

PMID- 15745271
TI  - Factors associated with the recent decline in suicide rates in the elderly in
      England and Wales, 1985-1998.
AB  - Elderly suicide rates have declined in recent years in several countries
      including England and Wales. This study examined the association between a trend
      of decline in age-specific suicide rates in the elderly in England and Wales and
      changes in various health and social factors for the period 1985 to 1998. Data on
      age-specific suicide rates was ascertained from the annual mortality statistics
      for the years 1985 to 1998. Data on the various health and social variables was
      ascertained from both the Statistics Division at the Department of Health and the
      Health and Personal Social Services Statistics, the yearly publications of the
      Department of Health from 1985 to 1998. The main findings of this study were (i)
      a significant negative correlation between the number of general practitioners
      and all categories of whole-time-equivalent (WTE) hospital medical staff and
      suicide rates for each of the four five-year age bands for males and females
      after the age of 65; (ii) a significant negative correlation between the number
      of new outpatient appointments for mental illness and suicide rates in males and
      females for each of the four five-year age bands between the ages 65-85 years;
      (iii) a significant positive correlation between the average daily number of
      available beds for mental illness and elderly suicide rates, for all five-year
      age bands between the ages 65-85 years; (iv) a significant negative correlation
      between the number of field social work staff and day centre staff and elderly
      suicide rates for each of the four five-year age bands after the age of 65 for
      males and females; and, (v) a significant positive correlation between the total
      number of elderly in all residential homes and the number of elderly in local
      authority residential homes and elderly suicide rates for each of the four five
      year age bands between the ages 65-85 years for males and females. A trend of
      decline in age-specific suicide rates in the elderly in England and Wales from
      1985 to 1998 was significantly associated with changes in various health and
      social variables. These included the number of general practitioners and hospital
      medical staff, the hospital psychiatric services, the number of local authority
      staff and the number of elderly residents in accommodation supported by a local
      authority. The results of this study suggest that changes in these variables may
      be important factors contributing to the recent decline in suicide rates but this
      effect should be viewed in the context of other health and social factors.

PMID- 15745272
TI  - Trends in suicide mortality in the deprived region of Epirus (north-west Greece)
      during the period 1998-2002.
AB  - This study determines the risk factors associated with suicide rates and the
      investigation of time trends in the deprived region of Epirus, north-west Greece,
      which is considered to be one of the least developed prefectures of the EU. Data
      selected demonstrated: (1) a mean age-standardized suicide rate per year of
      4.00/100,000 for males, 1.29/100,000 for females and 2.65/100,000 for the total
      population; (2) a significant rising trend of male suicides in the 35-44 and 65
      74 age groups; (3) a low female suicide rate in < 35 years age group and a
      relatively stable rate in the other age groups; (4) a significantly higher
      suicide rate in men than in women from both urban and rural areas and in older
      men from rural areas; (5) higher rates of suicide among widowed men and unmarried
      women; (6) the use of predominantly violent suicide methods, especially self
      shooting, hanging and drowning; (7) a significant peak in the total suicide rate
      in the spring and summer months and a decreased rate in September; and (8) three
      out of four of the suicide victims had consumed alcohol and/or other drugs before
      the act. Data reported here shows some remarkable trends compared to previous
      reports on suicide in Greece and other countries, probably due to cultural and
      life style characteristics of the study population.

PMID- 15745273
TI  - Accidental ligature strangulation deaths in East Delhi (India).
AB  - Ligature strangulations are usually homicidal. Accidental cases are quite
      uncommon, especially among adults. A retrospective ten-year study conducted in
      East Delhi revealed that in a total of 98 cases of death due to strangulation,
      five cases (approximately 5%) among all medico-legal deaths were of fatal
      ligature strangulation, involving adults who were neither intoxicated nor
      indulging in paraphiliac activity. The causative agent in three cases was a cycle
      rickshaw, in one case it was a rotatory part of a machine, and the fifth case
      occurred due to entanglement while tying up a cow. The cases and their autopsy
      findings have been described in this paper, together with the review and
      preventive aspects of such cases.

PMID- 15745274
TI  - Birth order and fratricide: an evaluation of Sulloway's hypothesis.
AB  - Sulloway (1996) suggested that older siblings were more likely to be fratricidal
      than younger ones. Our data, based on 113 case studies found in the psychiatric,
      psychological and criminological literature since 1959, confirms his hypothesis.
      In 72 out of the 92 cases (78%) where age could be determined, the aggressor was
      older than the victim. The same held true even when the age of aggressor, sex of
      aggressor and victim, presence or not of a blood tie, and presence of one or more
      victims are taken into account. Surprisingly, most of the aggressors in our
      sample were under the age of 18 years. Also, first-borns were more often the
      aggressor than the victim. This result seems to confirm the Adlerian theory of
      dethronement. Some suggestions and hypotheses are advanced for future research to
      improve our understanding of this phenomenon.

PMID- 15745275
TI  - Criminal abortion and concealment of birth in Transkei region, South Africa.
AB  - The objective was to estimate the incidence of criminal abortions and concealment
      of births in Transkei. This paper presents a review of the records of the medico
      legal register at Umtata General Hospital from 1993-2003. There were 37 cases of
      premature concealed births and conceptus material brought to the attention of
      medico-legal investigators between 1993 and 2003. Of these, 26 (70.3%) were
      concealed births, and 11 (29.7%) were abortion products. There is great
      variability in the incidence of abortion and concealment of births during this
      period. There were nine cases in 1993 and three in 2003. No case was reported in
      1994. There was only a single case reported in each of the years 1995, 1997 and
      2001, and four cases in each of the years 1996, 1998 and 2002. In 1998 there were
      eight cases, the highest for any year after promulgation of the Abortion Act.
      There is no significant difference in the number of cases reported for medico
      legal investigation of criminal abortion and concealment of births before and
      after the Abortion Act which came into effect in 1997.

PMID- 15745276
TI  - Laboratory evaluation of a new evidential breath-alcohol analyser designed for
      mobile testing--the Evidenzer.
AB  - The Evidenzer is a new kind of forensic breath-alcohol analyser, designed for use
      both at a police station (stationary) and also in a police vehicle (mobile) at
      the roadside. In this paper we report the accuracy and precision of the
      Evidenzer, determined under controlled laboratory conditions. The results were
      compared with a well-established breath-alcohol instrument (Intoxilyzer 5000S)
      and also with the concentration of alcohol in venous blood. Twenty healthy
      volunteers (10 men and 10 women) consumed ethanol (0.4 g/kg) in 15 minutes
      starting two to three hours after their last meal. Venous blood and breath were
      obtained for determination of ethanol at 15-30 minute intervals for up to four
      hours post-dosing. There was a good overall agreement between the two breath
      alcohol instruments and the mean bias was only 0.003 mg/L (95% limits of
      agreement of -0.016 to 0.023 mg/L). The standard deviation (SD) of measuring
      ethanol in breath was about the same for both instruments, being 0.006 mg/L, and
      this corresponds to a relative precision or coefficient of variation (CV) of
      4.7%. When the Evidenzer was used to analyse ethanol vapour (0.50 mg/L) generated
      from a wet-bath simulator, i.e. in-vitro conditions, the coefficient of variation
      was 0.7% indicating high analytical precision. The concentration of ethanol in
      venous blood and breath were highly correlated (r = 0.95) although systematic
      differences existed depending on time after drinking when comparisons were made.
      Both breath-alcohol instruments gave results higher than venous blood alcohol in
      tests made at 15 minutes after the end of drinking whereas at all later times the
      venous blood-alcohol concentration was higher

PMID- 15745277
TI  - Elderly suicide: an analysis of coroner's inquests into two hundred cases in
      Cheshire 1989 - 2001.
AB  - Elderly suicide is an index of more widespread disorder and discontent among the
      elderly, and furthermore is a potentially preventable cause of death. This study
      used coroner's inquest records of 200 elderly in Cheshire who killed themselves,
      and in which their unexpected deaths attracted a verdict of suicide.
      Sociodemographic characteristics, clinical aspects of the suicidal process and
      health care contact before death are reviewed. Unlike most available studies,
      cases of unexpected death in which an open verdict was given were not included in
      this study, which covered a 13 year period. The findings are interpreted and
      compared to the currently available literature on suicide in the elderly. Late
      life suicide is characterised by less warning, higher lethality and greater
      prevalence of depression and physical illness. However, suicide risk often
      remains undetected. All suicidal behaviour in the elderly should be taken
      seriously by psychiatric and primary care services, in order to reduce suicide
      rates in the elderly.

PMID- 15745278
TI  - An unusual case of suicide by broken glass pierced through the buttocks: a case
      report.
AB  - Suicidal stabbing to the back and buttocks is very unusual due to the limited
      accessibility of that region to the victim's hand. The following case report
      describes a 38-year-old man, known for depression and suicidal ideation, who was
      found deceased in his home after tearing his right internal iliac artery by
      stabbing himself through the buttock with a piece of glass from a broken beer
      bottle. The literature on suicidal stabbing, particularly focusing on the type of
      weapon and localisation of wounds, is reviewed.

PMID- 15745279
TI  - Usefulness of post-mortem ophthalmological endoscopy during forensic autopsy: a
      case report.
AB  - Post-mortem intraocular findings in two autopsy cases with traumatic intracranial
      haemorrhage were obtained using an ophthalmological endoscope. The endoscopy
      results clearly revealed the presence of intraocular haemorrhages and papilledema
      caused by intracranial haemorrhage. Post-mortem ophthalmological endoscopy offers
      several benefits. First, post-mortem intraocular findings can be directly
      observed in corpses with post-mortem clouding of the cornea. Secondly, the
      endoscopy only requires a 0.9 mm incision in the sclera and does not require the
      removal of the eye from the corpse, a procedure that should be avoided for
      ethical and cosmetic reasons. Thus, post-mortem opthalmological endoscopy is a
      useful method for obtaining intraocular findings in autopsies.

PMID- 15745280
TI  - Potential contamination of forensic entomology samples collected in the mortuary:
      a case report.
AB  - Carrion insects originating from infested bodies may establish small mortuary
      populations. Two Victorian Institute of Forensic Medicine cases are presented to
      illustrate how these insects can potentially contaminate forensic entomology
      samples collected in the mortuary. The first case proves that bodies can be
      colonised in the mortuary: when a decomposed body in freezer storage was thawed
      for a procedure in the main mortuary, it was colonised within five minutes of
      exposure by the beetle Necrobia rufipes De Geer (Cleridae, Coleoptera). The
      second case illustrates that immobile juvenile insects can be transferred between
      bodies, and describes the transfer of an Eristalis sp. (Syrphidae, Diptera) pupa
      from a decomposed to a fresh body. While the contamination risk is slight, it can
      be further minimised by checking mortuary-collected samples against those taken
      from the body discovery site, by mortuary pest control, and by checking previous
      mortuary admittance records for possible contamination sources.

PMID- 15745281
TI  - The IOM medical errors report: 5 years later, the journey continues.
AB  - In 1999, the Institute of Medicine released a report, To Err Is Human: Building a
      Safer Health System, which shed a new light for providers and patients across the
      nation looking at patient safety and medical errors. Since then, new ways of
      addressing patient safety have emerged. But how far does the healthcare system
      still have to go?

PMID- 15745282
TI  - IHI proposes six patient safety goals to prevent 100,000 annual deaths.
AB  - In an attempt to avoid 100,000 deaths a year in American hospitals, the Institute
      for Healthcare Improvement (IHI) proposed six new "changes of care" last month
      that have been "proven in both scientific literature and in experiences of at
      least some hospitals or hospital systems in the United States and abroad" to be
      effective in reducing mortality, according to IHI President Don Berwick.

PMID- 15745283
TI  - Drawbacks and limitations of computed tomography: views from a medical educator.

PMID- 15745285
TI  - Autotransplantation for central non-small-cell lung cancer in a patient with poor
      pulmonary function.
AB  - Lung resection is the standard therapy for non-small-cell lung cancer confined to
      the lung. The extent of pulmonary resection is dictated by the location and
      extent of the tumor and the patient's physiologic ability to tolerate resection.
      We present the case of a patient who had a large non-small-cell tumor of the lung
      that involved the right main stem bronchus and the adjacent pulmonary artery;
      poor pulmonary function precluded a pneumonectomy. Right upper and middle sleeve
      bilobectomy resection was performed, but reconstruction was not possible due to
      tethering by the intact lower lobe vein. Therefore, the remaining lower lobe was
      removed, and the lower lobe vein was divided and reimplanted into the upper lobe
      pulmonary venous stump. Cephalad advancement and autotransplantation of the lower
      lobe were then accomplished. These procedures allowed enough mobilization for
      direct bronchial and arterial reconstruction.

PMID- 15745284
TI  - Vasilii I Kolesov: a surgeon to remember.
AB  - Vasilii I. Kolesov (1904-1992) was one of the pioneers of cardiovascular surgery.
      He is often referred to as the surgeon who performed the first successful
      coronary artery bypass operation. Kolesov was the first to successfully apply the
      suture technique to clinical coronary artery bypass surgery. He was also the
      first--and remains the only--surgeon to use coronary stapling clinically. Recent
      rapid development in robotic and video-assisted coronary surgery has revived
      interest in Kolesov's original work on coronary stapling and off-pump coronary
      surgery. However, little is known about the personality of Dr. Kolesov, his early
      work that led to his pioneering effort, and the circumstances under which his
      work was done.

PMID- 15745286
TI  - The mechanical or electrical induction of medullary angiogenesis: will it improve
      sternal wound healing?
AB  - We induced angiogenesis in the tibial medulla and cortex of rabbits by electrical
      and mechanical stimulation, with the aim of future application to ischemic
      disease. Sixteen New Zealand rabbits were divided into 4 groups: in Group 1, a K
      wire was inserted into the medullary channel; in Group 2 a hole was drilled into
      the tibia; in Group 3, electrical stimulation was applied to the medullary
      channel; and in Group 4 (the control group), nothing was done. The interventions
      were applied during a 21-day period, after which all animals were evaluated
      scintigraphically and histopathologically. All 3 interventional groups were
      significantly superior to the control group in regard to medullary and cortical
      vascularity: the P values were 0.021 in all comparisons to control. However, the
      most fibrotic changes in the medulla occurred in the group that had been treated
      with electricity (P = 0.008). Slight fibrotic changes occurred in the hole group
      (P = 0.040), and none occurred in the K-wire group. In sum, all 3 interventions
      are capable of inducing medullary angiogenesis, but electricity is inferior in
      regard to fibrotic change. We believe that this present study can establish a
      baseline for further work that explores clinical applications to problematic
      ischemic conditions, including delayed sternal wound healing after cardiac
      surgery.

PMID- 15745287
TI  - Computer-assisted detection of systolic murmurs associated with hypertrophic
      cardiomyopathy: a pilot study.
AB  - A pilot study was conducted to ascertain the level of agreement between
      auscultatory findings derived from heart sound recordings by a cardiologist and
      the results of a computer-based heart sound analysis algorithm. Heart sound
      recordings were obtained from volunteer subjects previously diagnosed with
      hypertrophic cardiomyopathy. Twenty-second recordings were obtained at each of 4
      standard auscultatory locations on the precordium in 2 postures: standing and
      reclining. Detailed auscultatory findings were derived by a cardiologist, who
      listened to the heart sound recordings and was blinded to the study design. The
      recordings were analyzed by an algorithm that detects heart sounds and murmurs,
      and derives associated timing and energy parameters. The algorithm results were
      compared with the auscultatory findings provided by the cardiologist and
      correlated with the medical histories provided by the volunteer subjects. A high
      degree of concordance between the medical histories, auscultatory findings, and
      computer analyses was obtained. The 1st and 2nd heart sounds were detected with
      high sensitivity (90.7%) and positive predictivity (93.0%). Systolic murmurs were
      detected with a sensitivity that increased from 50% for grade 1 to 100% for
      grades 2-3 and 3. The signal energy in the mid-frequency range correlated well
      with murmur grade judgments, and also agreed well with the cardiologist's
      judgments of the relative loudness of murmurs in standing versus reclining
      postures. The computer analysis algorithm thus instantiates the objective
      detection and identification of apical systolic murmurs that are louder in
      standing than in reclining postures; such murmurs are a cardinal sign of
      hypertrophic obstructive cardiomyopathy.

PMID- 15745289
TI  - Surgical treatment of aortic abscess and fistula.
AB  - The formation of annular abscess and fistulous communication, the most
      devastating complication of destructive aortic valve endocarditis, requires
      extensive surgical debridement. Five men experienced destructive native aortic
      valve endocarditis in association with congestive heart failure (New York Heart
      Association functional class IV) and hemodynamic deterioration that developed
      from severe aortic regurgitation. To eradicate the aortic valve endocarditis, we
      performed (from July 1998 through November 2002) aortic annular skeletonization
      by dissecting all infectious and necrotic tissue within the abscess cavity and
      the fistula between the ventriculoarterial junction and the sinotubular junction.
      The completely resected annular area was covered with a glutaraldehyde-treated
      autologous pericardial patch that was sutured firmly to fibrous tissue, for a
      secure proximal anastomosis. Reconstruction of the aortic root was followed by
      implantation of a Freestyle stentless bioprosthesis, using the aortic root
      replacement technique. There were no deaths after surgery, nor is there record of
      a permanent complication due to a loss of conduction tissue. All 5 patients were
      in New York Heart Association functional class I or II during follow-up (range, 8
      56 months). Echocardiography showed no signs of valve dysfunction, recurrent
      endocarditis, or fistulation. Annular skeletonization and reconstruction of the
      aortic annulus with glutaraldehyde-treated autologous pericardium permits radical
      removal of infected tissue and effective treatment of aortic annular abscess,
      with less risk of valve dehiscence from the fragile aortic annulus.

PMID- 15745288
TI  - Evaluation of flow characteristics of the left internal thoracic artery graft:
      perioperative color Doppler ultrasonography versus intraoperative free-bleeding
      technique.
AB  - From October 2000 through April 2001, we prospectively evaluated the flow
      characteristics of the left internal thoracic artery (LITA) graft in a homogenous
      group of 44 men with isolated severe proximal left anterior descending coronary
      artery stenosis who underwent elective coronary artery bypass grafting with
      cardiopulmonary bypass. We performed transthoracic color Doppler ultrasonography
      preoperatively and repeated this examination in each patient between the 5th and
      7th postoperative days, obtaining cross-sectional area, total flow volume,
      diastolic velocity, systolic velocity, mean velocity, pulsatility index, and
      resistance index. These results were compared with those of the intraoperative
      free-bleeding technique. Good-quality Doppler images of the LITA were easily
      obtained with a combined supraclavicular-parasternal approach. After surgery,
      systolic flow velocity, pulsatility index, and resistance index decreased
      significantly, but diastolic flow velocity and mean flow velocity increased
      significantly. The intraoperative flow volume obtained by the free-bleeding
      technique (32.42 +/- 12.33 mL/min) was significantly less than both pre- and
      postoperative ultrasonographic values (42.22 +/- 10.77 mL/min and 45.36 +/- 19.52
      mL/min, respectively). No significant difference was found when changes in LITA
      values were compared between patients with (n=19) and without (n=25) normal
      anterior wall motion. We conclude that color Doppler ultrasonography is a
      reliable noninvasive technique for preoperative evaluation of the LITA as a graft
      and for postoperative long-term follow-up of graft function. However the
      intraoperative free-bleeding technique is not reliable for flow-volume
      measurement due to anesthesia-related hemodynamic changes and vasospasm. Color
      Doppler can prevent useless LITA harvesting and decrease the need for
      postoperative LITA angiography.

PMID- 15745290
TI  - Bentall procedure using cryopreserved valved aortic homografts: mid- to long-term
      results.
AB  - The Bentall procedure is the standard operation for patients who have lesions of
      the ascending aorta associated with aortic valve disease. In many cases, however,
      mechanical prosthetic conduits are not suitable. There are few reports in the
      English-language medical literature concerning the mid- to long-term outcome of
      Bentall operations with cryopreserved homografts. Therefore, we reviewed our
      experience with this procedure and valved homografts. From January 1997 through
      December 2002, 21 patients underwent a Bentall operation with cryopreserved
      homografts at our institution. There were 14 males and 7 females; the mean age
      was 36 +/- 21 years (range, 15-74 years). Eleven patients had undergone previous
      aortic valve surgery. All patients had aortic dilatation or aneurysms involving
      the ascending aorta. Indications for surgery included aortic valve stenosis or
      insufficiency, and aortic valve endocarditis (native valve or prosthetic). One
      patient had Takayasu's arteritis and 3 had Marfan syndrome. There was 1 hospital
      death (due to sepsis), but no other major postoperative complications. The mean
      hospital stay was 14 +/- 7 days. Follow-up echocardiographic and computed
      tomographic scans were performed yearly. The mean follow-up was 34 months (6-72
      months). Follow-up imaging revealed no calcifications or degenerative processes
      related to the homograft. Four patients had minimal valve regurgitation. Two
      patients died during follow-up. The 3-year actuarial survival rate was 85.7%. Our
      data suggest that the Bentall procedure with a valved homograft conduit is a safe
      procedure with excellent mid- to long-term results, comparable to results
      reported with aortic valve replacement with a homograft.

PMID- 15745291
TI  - Passive infusion: a simple delivery method for retrograde cardioplegia.
AB  - Some damage to the capillaries and increase in myocardial edema have been shown
      when retrograde cardioplegia perfusion pressure exceeds 40-50 mmHg, or possibly
      when it falls within this pressure interval. To avoid these complications, we
      designed a very simple delivery method for retrograde cardioplegia: passive
      continuous infusion by gravitational force alone. From August 2002 through April
      2003, 147 patients undergoing elective coronary artery bypass surgery were
      randomly allocated into 2 groups. In both groups, isothermic blood cardioplegic
      solution was infused continuously in a retrograde fashion, after antegrade
      cardioplegic arrest. Group 1 (n=76) received retrograde infusion passively by
      gravitational force, while Group 2 (n=71) received retrograde infusion from a
      manually controlled pressure bag, with the pressure maintained at about 40 mmHg.
      Myocardial biopsy specimens were taken just before the aorta was declamped, and
      myocardial edema was scored upon histopathologic examination. Postoperative
      myocardial damage was evaluated with periodic measurements of CK-MB isoenzyme and
      cardiac troponin T levels. We recorded cardioplegic infusion pressures and rates,
      and the total amount of potassium administered. The mean cardioplegic infusion
      pressures and rates, total potassium levels, and cardioplegic solution amounts
      were significantly lower in Group 1 than Group 2. Histologic observations
      revealed significantly less myocardial edema in Group 1. There were no
      differences between groups in CK-MB isoenzyme or cardiac troponin T levels,
      mortality, or morbidity. Retrograde continuous infusion of isothermic blood
      cardioplegic solution by gravitational force alone appears to provide
      satisfactory myocardial protection and to eliminate the harmful effects of higher
      pressures upon the myocardium.

PMID- 15745293
TI  - End-stage heart failure with multiple intracardiac thrombi: a rescue strategy.
AB  - The use of ventricular assist devices as a bridge to transplantation has become a
      widely used option for patients with end-stage heart failure. In contrast to
      total artificial hearts, ventricular assist devices support the failing heart by
      bypassing one or both ventricles. In certain cases (myocardial tumors, graft
      failure, transplant rejection, endocarditis, intracardiac thrombus formation),
      however, it may be advantageous to excise the heart and replace it with an
      artificial device. Total artificial hearts are intracorporeal devices designed
      for this purpose. Unfortunately, some patients are too small or are, for other
      reasons, ineligible for a total artificial heart. We describe the case of a 55
      year-old woman who had ischemic cardiomyopathy and thrombus formation in all 4
      cardiac chambers. To reduce the risk of thromboembolic events, we elected to
      replace her heart completely with 2 extracorporeal ventricular assist devices.
      The heart was excised via a median stemotomy approach, and the outflow cannulae
      (from device to patient) were connected to both atrial remnants. The 2 inflow
      cannulae (from patient to device) were anastomosed end-to-end to the aorta and
      the pulmonary artery, respectively. After attaining a flow of more than 5 L, the
      2 extracorporeal assist devices effectively and efficiently performed the work of
      the native heart. Thus re-established, organ perfusion was improved by this
      mechanically driven circulation, as signified by an initial decrease in
      creatinine and blood urea nitrogen levels. The patient, however, did not recover
      from postoperative neurological dysfunction and died of respiratory insufficiency
      and multiple-organ failure on the 26th postoperative day.

PMID- 15745292
TI  - Pericardial tamponade and large pericardial effusions: causal factors and
      efficacy of percutaneous catheter drainage in 50 patients.
AB  - In 50 patients treated from January 1998 through March 2002 for pericardial
      effusion and tamponade, we retrospectively investigated the efficacy of
      percutaneous placement of an indwelling pericardial catheter guided by 2
      dimensional echocardiography and fluoroscopy. We also investigated causation. In
      80% of the patients, we were able to determine specific causes through clinical,
      serologic, and cytologic investigation: cancer in 15 patients, chronic renal
      failure in 11, systemic lupus erythematosus in 2 rheumatoid arthritis in 2,
      Dressler syndrome in 2, tuberculosis in 1, blunt chest trauma in 1, purulent
      pericarditis in 1, and probably viral pericarditis in 5. No specific cause could
      be determined in 10 patients (20%). We did not observe any complication due to
      the procedure. Two patients died during hospitalization. After hospitalization, 9
      patients with metastatic cancer died within 3 months. A 2nd percutaneous drainage
      procedure was required in 2 cancer patients. Recurrence of pericardial effusion
      and tamponade and the requirement of pericardiectomy occurred in 2 patients with
      perfusion of unknown cause and in 1 patient with perfusion due to rheumatoid
      arthritis. Histologic examination of pericardial tissue in patients with
      idiopathic disease showed fibrinous pericarditis but no causal factor. In the
      group with idiopathic pericardial effusion, 2 patients with multiple mediastinal
      lymphadenopathy underwent mediastinal exploration; biopsy revealed nonspecific
      lymphadenitis and fibrinous pericarditis. In patients with large pericardial
      effusions and tamponade, the specific cause was in most cases already known or
      obtained by initial clinical and laboratory investigation. Sufficient cardiac
      decompression was achieved by percutaneous pigtail catheter drainage.

PMID- 15745294
TI  - Coronary artery surgery in women. 1974.

PMID- 15745295
TI  - Combined tricuspid valvuloplasty and superior cavopulmonary anastomosis for
      repair of traumatictricuspid valve injury.
AB  - Chronic tricuspid valve insufficiency secondary to blunt chest trauma is rare in
      the pediatric population, with fewer than 10 cases reported. Surgical repair has
      focused on the tricuspid valve. We present 2 cases of traumatic tricuspid valve
      insufficiency in pediatric patients after blunt chest trauma in whom tricuspid
      valve repair was performed along with superior cavopulmonary anastomosis. To our
      knowledge, this is the 1st report of the use of this combination of surgical
      procedures for repair of traumatic tricuspid regurgitation in either adults or
      children.

PMID- 15745297
TI  - Use of a handheld epicardial ultrasonic Doppler flow detector to locate an
      intramyocardial coronary artery encased in inflamed neoplastic pericardium.
AB  - A 44-year-old man had severe stenosis of the left main coronary artery. The
      middle portion of the left anterior descending coronary artery was in an
      intramyocardial location. The pericardium, ascending aorta, epicardium, and
      coronary arteries were encased by a metastatic, poorly differentiated papillary
      adenocarcinoma. The left anterior descending artery was located with the aid of a
      handheld epicardial ultrasonic Doppler flow detector, and grafted with the left
      internal thoracic artery on a beating heart. Subsequently, the patient underwent
      10 cycles of chemotherapy More than 22 months later, he was asymptomatic and in
      remission from neoplastic disease.

PMID- 15745296
TI  - Vasoplegic syndrome after off-pump coronary artery bypass surgery: an unusual
      complication.
AB  - We report the case of a 65-year-old man who developed norepinephrine-resistant
      vasoplegic syndrome after elective off-pump coronary artery bypass surgery
      (OPCAB). The failure of norepinephrine to improve the patient's hemodynamics
      prompted us to start treatment with vasopressin; within 30 minutes, the
      hemodynamics began to improve. After 12 hours, the patient was stable enough to
      be weaned from the vasopressin. He was discharged from the hospital on the 10th
      postoperative day. To our knowledge, ours is the 1st report of vasopressin use
      for vasodilatory shock after OPCAB in the English-language medical literature.
      Herein, we discuss the pathophysiology and management of vasoplegic syndrome-
      which is controversial--with special emphasis on the use of vasopressin in this
      situation.

PMID- 15745298
TI  - Asymptomatic severe aortic coarctation in an 80-year-old man.
AB  - Survival to advanced age is exceptional in patients with unrepaired aortic
      coarctation. We report the case of a hypertensive 80-year-old man with
      coarctation of the aorta who was otherwise asymptomatic. Coarctation was
      suspected when a femoral-radial pulse delay was noted during his routine physical
      examination. A 25-mmHg systolic blood pressure gradient between the upper and
      lower extremities was detected. Subsequent magnetic resonance angiography,
      aortography, and coronary angiography revealed severe coarctation of the aorta,
      well-developed collateral vessels, and severe coronary artery disease that
      included the left main artery. Coronary artery bypass grafting was performed, and
      the coarctation was managed conservatively with antihypertensive medication. At
      the 1-year follow-up visit, the patient was still asymptomatic and maintained a
      normal blood pressure with medication.

PMID- 15745299
TI  - Floating thrombus in the proximal aortic arch.
AB  - Floating thrombus in the aortic arch is an unusual source of systemic embolism.
      Surgical removal of the thrombus is a therapeutic option, because thrombolytic
      therapy carries the risk of partial lysis and repeat embolization. We report a
      case involving a large floating thrombus that originated in the proximal aortic
      arch and extended into the left subclavian artery and the descending aorta, and
      we discuss the surgical management.

PMID- 15745300
TI  - Aorta-left renal vein fistula in a woman.
AB  - Spontaneous rupture of an abdominal aortic aneurysm into a retroaortic left renal
      vein is an uncommon occurrence. A 55-year-old woman presented with shortness of
      breath, vomiting, and diffuse abdominal pain that had radiated to her back and
      legs for the preceding 10 days. A pulsatile abdominal mass, hematuria, renal
      insufficiency, and heart failure were present at the initial evaluation. Computed
      tomography showed an infrarenal abdominal aortic aneurysm that communicated with
      a retroaortic left renal vein. After urgent surgical repair, cardiac and renal
      function were dramatically improved. To the best of our knowledge, this is the
      1st reported case of a woman with such a fistula. We review treatments reported
      in the literature.

PMID- 15745301
TI  - Cardiac Aspergillosis with pedunculated mass in the left ventricle.
AB  - Immunosuppression can allow organisms that are not usually pathogenetic to cause
      disease; under such circumstances, Aspergillus species frequently form large
      masses of fungal elements. We describe the case of a 12-year-old girl with
      hematologic remission of leukemia. She had a left ventricular pedunculated mass
      that was detected by echocardiographic study; at surgery, the presence of
      Aspergillus terreus was confirmed.

PMID- 15745302
TI  - Dual coronary emboli in peripartum cardiomyopathy.
AB  - Coronary emboli are rare but devastating events. We present the case of a 31-year
      old woman with peripartum cardiomyopathy and mural thrombus. She was admitted
      with an acute, non-ST elevation myocardial infarction. Two emboli were seen on
      the coronary angiogram: one in the left anterior descending coronary artery and a
      second in the left circumflex artery. Each embolus resolved after local infusion
      of eptifibatide at the time of angiography. There has been 1 report in the
      English-language medical literature of a similar coronary embolic event in the
      setting of peripartum cardiomyopathy; however, in that case, only 1 embolus was
      found. Our case further documents embolic coronary occlusion as a consequence of
      peripartum cardiomyopathy.

PMID- 15745303
TI  - Cardiac ochronosis: valvular heart disease with dark green discoloration of the
      leaflets.
AB  - We report the case of 67-year-old woman who underwent aortic valve replacement
      and mitral valve repair due to ochronotic valvular disease (alkaptonuria), which
      was diagnosed incidentally during cardiac surgery.

PMID- 15745304
TI  - Double papillary fibroelastoma of the aortic valve.
AB  - A case of asymptomatic aortic valve fibroelastoma was diagnosed by transthoracic
      and transesophageal echocardiography in a 77-year-old man. A 2nd tumor was found
      at surgery. Both fibroelastomas were removed surgically without aortic valve
      replacement. During surgical excision of a cardiac fibroelastoma, the entire area
      surrounding the lesion should be inspected carefully for additional lesions. Such
      lesions can be missed on echocardiographic evaluation.

PMID- 15745305
TI  - Quadricuspid aortic valve.

PMID- 15745306
TI  - Right atrial hydatid cyst prolapsing into the tricuspid valve.

PMID- 15745307
TI  - Cardiac, aortic, and esophageal involvement of a large lymphoma.

PMID- 15745308
TI  - Perforation of the right ventricular wall by temporary pacemaker wire.

PMID- 15745309
TI  - Large ascending thoracic aortic aneurysm with protruding pseudoaneurysm.

PMID- 15745310
TI  - Anabasis of PTCA.

PMID- 15745311
TI  - Procoagulant potential of platelet alpha granules.
AB  - In this brief review of the literature it is pointed out that during platelet
      activation and degranulation platelet alpha granules leave the platelet interior
      through blebs in platelet plasma membrane and through the tips of the pseudopods,
      and then accumulate in the external milieu. There they undergo disintegration and
      secondary adhesion to the platelet plasma membranes. During their disintegration
      they expose their tightly packed GPIIb-IIIa complexes, annexin V stainable
      aminophospholipids, factor V, and the membrane markers CD62 and CD63. There is
      also demasking of lysosomal acid phosphatase activity and microvesicle formation.
      Lysosomal nature of platelet alpha granules is mentioned. It is suggested that
      platelet alpha granules are the sole source of platelet procoagulant activity and
      platelet microparticles (MP) or microvesicles (MV). The implications of this
      concept for antiplatelet therapy are discussed. A relationship of this process to
      tissue factor exposure and apoptosis is suggested.

PMID- 15745312
TI  - Pharmacodynamic enhancement of the anti-platelet antibody fab abciximab by site
      specific pegylation.
AB  - Monoclonal antibodies have been firmly established as human therapeutics. Their
      high affinity and specificity for target antigens minimize adverse reactions and
      their molecular size results in extended circulation times relative to small
      molecule pharmaceuticals. The ability to customize the pharmacokinetics in a
      rational manner can enhance the potential for these and other classes of
      biologicals. We have systematically studied the effect of site-specific
      pegylation of the Fab' fragment of the anti-GPIIb/IIIa, alphavbeta3 antibody
      c7E3. Regardless of the molecular weight of the PEG molecules, the intrinsic
      affinity of the resulting constructs remained unchanged. However, in functional
      assays measuring inhibition of platelet aggregation, the calculated IC50 values
      of the conjugates decreased with increasing molecular weight of the conjugated
      PEG. It was determined that the molecular size of the conjugates affects antigen
      accessibility and whereas high levels of binding to antigen molecules on cells
      with high antigen density can be demonstrated with the Fab fragment, comparable
      levels are not achievable with large molecular weight conjugates. In spite of the
      inability of the larger PEG constructs to achieve saturation binding, functional
      inhibition of platelet aggregation consistent with saturation binding was
      demonstrated and the increased molecular size of the conjugates led to
      predictably prolonged inhibition of platelet aggregation.

PMID- 15745313
TI  - Von Willebrand factor can support platelet aggregation via interaction with
      activated GPIIb-IIIa and GPIb.
AB  - In this study we investigated mechanisms of platelet interaction with von
      Willebrand factor (vWF) induced by activating anti-glycoprotein (GP)IIb-IIIa
      antibody CRC54 directed against LIBS (ligand-induced binding site epitope) in
      GPIIIa. It was demonstrated that aggregation of washed platelets (measured in
      Born aggregometer) could be stimulated by CRC54 not only in the presence of
      fibrinogen but vWF as well. The level of aggregation induced in the presence of
      saturating concentrations of vWF (approximately 80 microg/ml) was even higher
      than that in the presence of 1 mg/ml of fibrinogen. Aggregation supported by vWF
      unlike fibrinogen supported aggregation was almost completely inhibited not only
      by GPIIb-IIIa antagonists (F(ab')2 fragment of blocking anti-GPIIb-IIIa antibody
      CRC64 and peptidomimetic aggrastat) but also by anti-GPIb blocking antibody AK2.
      Aggregation response induced by CRC54 in the presence of vWF was much lower when
      normal platelets were substituted with GPIb-deficient platelets and this residual
      aggregation was not affected by anti-GPIb antibody AK2 but still inhibited by
      anti-GPIIb-IIIa blocking antibody fragment. CRC54-induced aggregation supported
      by vWF (as well as by fibrinogen) was only partially inhibited by prostaglandin
      E1, indicating that at least its initiation does not require activation of
      platelets. CRC54, both in the presence of vWF and fibrinogen, failed to stimulate
      serotonin secretion at physiological Ca2+ concentration of 1 mM, although
      substantial release reaction was detected when Ca2+ concentration was decreased
      to 0.1 mM. CRC54 could also stimulate platelet interaction with immobilized vWF
      and fibrinogen. However, unlike platelet aggregation in suspension mediated by
      flow phase vWF, platelet adhesion to adsorbed vWF (in a same way as to
      fibrinogen) was inhibited only by GPIIb-IIIa but not GPIb antagonists. The data
      obtained indicated that vWF support platelet aggregation induced by activating
      anti-GPIIb-IIIa via interaction with two receptors - activated GPIIb-IIIa and
      GPIb.

PMID- 15745314
TI  - Distinct roles of ligand affinity and cytoskeletal anchorage in alphaIIbbeta3 (GP
      IIb/IIIa)-mediated cell aggregation and adhesion.
AB  - Platelet integrin alphaIIbbeta3 (GP IIb/IIla) is functionally modulated by
      changes in ligand affinity or in cytoskeletal anchorage. CHO cells transfected
      with wild-type/mutated alphaIIbbeta3 allow the dissection of the relative
      contributions of the two regulatory mechanisms in alphaIIbbeta3-mediated adhesion
      and aggregation. Mutations included a truncation of the cytoplasmic domain of the
      beta-subunit, resulting in a loss of cytoskeletal anchorage of alphaIIbbeta3, and
      a VGFFK-deletion of the alpha-subunit, resulting in a permanent high affinity
      state. alphaIIbbeta3-mediated cell aggregation is dependent on the high affinity
      state but only partially on the cytoskeletal anchorage of alphaIIbbeta3. In
      contrast, alphaIIbbeta3-mediated cell adhesion is dependent on the cytoskeletal
      anchorage but only partially on the high affinity state of alphaIIbbeta3. Thus,
      the functional evaluation of mutated alphaIIbbeta3 implies a differential role of
      affinity state and cytoskeletal anchorage for alphaIIbbeta3-mediated cell
      adhesion and aggregation.

PMID- 15745315
TI  - The PFA-100 detects sub-optimal antiplatelet responses in patients on aspirin.
AB  - Although it is suspected that some patients with acute coronary syndromes (ACS)
      could have a sub-optimal response to aspirin (SASAR), currently a fixed dose of
      ASA is long-term used in all individuals. This study was designed to determine
      SASAR and whether a SASAR is a predictor for recurrence of ischemic events in
      patients on low-dose ASA with a previous ACS. One hundred patients taking ASA 100
      mg/day were assessed at 1 and 6 months after a first ACS. SASAR was initially
      defined as a failure of the ASA treatment to significantly prolong the closure
      time in the Platelet Function Analyzer (PFA-100). SASAR in these samples was
      reconfirmed by conventional aggregometry. TXB2 levels were determined in plasma.
      At one month 49 patients showed SASAR in the PFA-100; only 25 of them showed
      SASAR by conventional aggregometry. At six months, 39 of 81 patients showed SASAR
      by PFA-100, but conventional aggregometry detected SASAR in only 12 of the 39
      patients. TXB2 levels were significantly higher in patients with SASAR. Five
      patients with SASAR, by both tests, died during follow-up (p = 0.013). The PFA
      100 detected a high rate of SASAR in patients with ACS. This instrument could be
      used to screen for suboptimal response to the antiplatelet action of ASA. Whether
      persistence of SASAR could relate to a higher risk of recurrence and how
      adjusting the dose of ASA could reduce the rate of SASAR are issues that deserve
      further investigations.

PMID- 15745316
TI  - Abnormal vascular, platelet and coagulation markers in primary thrombocythaemia
      are not reversed by treatments that reduce the platelet count.
AB  - Although the primary aim of the treatment of primary thrombocythaemia is to
      reduce platelet counts, its effect on platelet activation, vascular dysfunction
      and coagulopathy, which are also abnormal, is unknown. We therefore hypothesised
      that successful treatment of primary thrombocythaemia is accompanied by an
      improvement in markers of these processes. To test this hypothesis, we compared
      38 patients with 15 healthy age and sex-matched controls. Seven untreated
      patients had platelet counts higher than those 31 on treatment, that were in turn
      higher than the 15 controls (all p < 0.01). Plasma fibrinogen, P-selectin, von
      Willebrand factor and sVCAM were higher in both patient groups compared to
      controls (all p < 0.05), but not between patient groups. sE-selectin and sICAM
      were unaltered between the three groups. D-dimers were higher in treated patients
      than in controls. We conclude that successful thrombocytosis treatment does not
      normalise markers of coagulation, platelet, or endothelial pathophysiology. This
      may account for continuing risk of pathology in those whose platelet counts have
      been normalised.

PMID- 15745317
TI  - Corticosteroid administration depresses circulating dendritic cells in ITP
      patients.
AB  - Idiopathic or immune thrombocytopenic purpura (ITP) is an autoimmune disorder
      characterized by low platelet count resulting from antibody-mediated destruction
      of platelets. The production of these IgG anti-platelet autoantibodies is
      critically governed by T-lymphocytes which can be activated by antigen-presenting
      cells (APC) such as dendritic cells. We hypothesized that one of the mechanisms
      by which corticosteroid administration can suppress the immune system is to
      depress the number of circulating dendritic cells production in ITP patients.
      Dendritic cell population was measured in peripheral blood of three ITP patients
      before and after the administration of prednisone. Both counts of myeloid and
      lymphoid dendritic cells in the blood of ITP patients were greatly reduced after
      the administration of prednisone. The decrease in circulating dendritic cells is
      associated with the increase of platelets in circulation with the treatment of
      prednisone. These results suggest that corticosteroid therapy may decrease the
      effects of the autoantibody on platelets in ITP patients by reduce the number of
      circulating dendritic cells.

PMID- 15745318
TI  - Platelet aggregation induced by the C-terminal peptide of thrombospondin-1 (4N1
      1) is inhibited by epigallocatechin gallate but not by prostaglandin E1.
AB  - The C-terminal peptide of thrombospondin (4N1-1) stimulates distinct signalling
      pathways but induces an activation-independent platelet aggregation. This study
      demonstrates inhibitory effects of epigallocatechin gallate (EGCG), a major
      flavonoid component of green tea, on 4N1-1-induced aggregation of washed human
      platelets. Thrombin (0.1 U/ml)-induced platelet aggregation was completely
      inhibited by prostaglandin E1 (PGE1, 300 nM). In contrast, platelet aggregation
      induced by 4N1-1 (100 microM) was not affected by PGE1. However, epigallocatechin
      gallate (EGCG), but not other catechins from green tea, concentration-dependently
      inhibited 4N1-1-induced platelet aggregation. Thus, dietary components, such as
      EGCG, may inhibit platelet function even under conditions, when 'classical'
      platelet inhibitors, such as cAMP-elevating agents, are not effective.

PMID- 15745319
TI  - Antigen density of P-selectin (CD 62P) on the platelets of healthy term newborns.
AB  - Measurements have been made of the antigen density of P-selectin (CD 62P) on the
      surface of platelets of healthy term newborns in relation to sex and in different
      umbilical vessels. The effect of thrombin or ADP on the density of CD 62P has
      been determined. The study was performed in 18 healthy term newborns, 10 girls
      and eight boys. Dako QIFIKIT was applied to calculate the number of these
      antigens. No differences were observed in the number of antigens of CD 62P on
      newborn platelets between the umbilical vein and artery in both sexes. On the
      other hand, boys demonstrated 31,245 antigens/plt, girls 26,397/plt (P = 0.045).
      A statistically significant increase in the expression of CD 62P was also
      observed following activation of thrombin in both sexes and in the umbilical vein
      and artery. ADP as a weaker agonist demonstrated less changes. A high number of
      the CD 62P antigens on the platelets of newborns may be interpreted as an effect
      of increased thrombinogenesis during birth. It can be suggested that this process
      is more pronounced in boys than girls.

PMID- 15745320
TI  - Elective stenting, platelet serotonin and thrombotic events.

PMID- 15745321
TI  - The National Action Plan for the Prevention and Control of Non-communicable
      Diseases and Health Promotion in Pakistan--Prelude and finale.
AB  - In Pakistan a public-private partnership--led by the NGO Heartfile and
      constituted additionally by the Ministry of Health, Government of Pakistan and
      the WHO Pakistan office--was launched in April 2003. Mandated with the task of
      developing and implementing a national strategy for achieving national goals for
      the prevention and control of non-communicable diseases (NCDs). This was the
      first opportunity to mount a truly 'National Plan of Action' in Pakistan
      enlisting a broader range of inputs and with the Governments commitment to NCD as
      a priority. The partnership recently released a strategic framework for action-
      the National Action Plan for the Prevention and Control of Non-communicable
      Diseases and Health Promotion in Pakistan (NAP-NCD)--an integrated and concerted
      approach addressing the multidisciplinary range of issues within a prevention and
      control framework across a broad range of NCDs. Incorporating both policies and
      actions and set within a long-term and life course perspective, NAP-NCD calls for
      an institutional, community and public policy level change factoring integration
      at four levels: grouping NCDs so that they can be targeted through a set of
      actions, harmonizing actions, integrating actions with existing public health
      systems and incorporating contemporary evidence-based concepts with this
      approach. The NAP-NCD delivers an Integrated Framework for Action, which has been
      modelled to impact a set of indicators through the combination of range of
      actions in tandem with rigorous formative research. Drawing on the strengths of
      various public and private sector partners, this programme outlines a scope of
      interventions that are built on shared responsibility, allowing agencies to
      participate according to their own missions and mandates. The partnership is in
      harmony with national health priorities, complements state initiatives and is
      optimally integrated with the national health system. The partnership has brought
      value to all the three partners. The government has harnessed the technical
      strength of a private sector partner, which in turn is contributing to the
      country's National Plan within the framework of priorities set by broad-based
      national consensus; WHO, on the other hand, is gaining experience in working in a
      country model in which the private sector can be supported through WHO country
      resources, which are typically earmarked for public sector initiatives. Work is
      currently underway to implement the first phase of NAP-NCD.

PMID- 15745322
TI  - The National Action Plan for the Prevention and Control of Non-communicable
      Diseases and Health Promotion in Pakistan--Common action area.

PMID- 15745323
TI  - The National Action Plan for the Prevention and Control of Non-communicable
      Diseases and Health Promotion in Pakistan--Cardiovascular diseases.
AB  - The National Action Plan for Non-Communicable Disease Prevention, Control and
      Health Promotion in Pakistan (NAP-NCD) incorporates prevention and control of
      cardiovascular diseases (CVD) as part of a comprehensive and integrated non
      communicable Disease (NCD) prevention effort. In this programme, surveillance of
      cardiovascular risk factors is part of an integrated population-based NCD
      surveillance system. The population approach to CVD prevention is a priority area
      in this programme with a focus on broad policy measures and behavioural change
      communication. The former include revision of the current policy on diet and
      nutrition to expand its focus on under-nutrition; the development of a physical
      activity policy; strategies to limit the production of, and access to, ghee as a
      medium for cooking and agricultural and fiscal policies that increase the demand
      for, and make healthy food more accessible. The programme focuses attention on
      improving the quality of prevention programmes within primary and basic health
      sites and integrates concerted primary and secondary prevention programmes into
      health services as part of a comprehensive and sustainable, scientifically valid,
      and resource-sensitive programme for all categories of healthcare providers. It
      promotes screening for raised blood pressure at the population level and
      screening for dyslipidaemia and diabetes in high-risk groups only. It highlights
      the need to ensure the availability of aspirin, beta blockers, thiazides, ACE
      inhibitors, statins and penicillin at all levels of healthcare. The programme
      points out the need to conduct clinical end-point trials in the native Pakistani
      setting to define cost-effective therapeutic strategies for primary and secondary
      prevention of CVDs. Emphasis is laid on building capacity of health systems in
      support of CVD prevention and control and building a coalition or network of
      organizations to add momentum to CVD prevention and control efforts.

PMID- 15745324
TI  - Diabetes prevention and control: National Action Plan for NCD Prevention, Control
      and Health Promotion in Pakistan.
AB  - More than 10% of the adult population in Pakistan suffers from diabetes. The
      National Action Plan for Non-communicable Disease Prevention, Control and Health
      Promotion in Pakistan (NAP-NCD) incorporates prevention and control of diabetes
      as part of a comprehensive and integrated national non-communicable disease (NCD)
      prevention effort. Building on existing data, the diabetes surveillance process
      has been integrated with a comprehensive population-based NCD surveillance system
      using waist circumference as a proxy indicator for the risk of diabetes in the
      short term; however, the surveillance strategy makes a case for future efforts to
      upgrade surveillance to allow a more comprehensive assessment incorporating
      biochemical assessments. The programme focuses on diabetes prevention by
      maximizing risk factor control as a common theme across the range of NCDs and
      lays emphasis on integrating prevention of'diabetes and intensified case finding
      in high-risk groups into health services as part of a comprehensive and
      sustainable, scientifically valid, culturally appropriate and resource-sensitive
      Continued Medical Education (CME) programme for all categories of healthcare
      providers. The programme also focuses on ensuring availability of anti-diabetics
      (insulin, sulphonylureas, metformin) at all levels of healthcare. Building
      capacity in the health system and coalitions in support of diabetes prevention
      has also been regarded as being critical.

PMID- 15745325
TI  - Tobacco control: National Action Plan for NCD Prevention, Control and Health
      Promotion in Pakistan.
AB  - Reliance on revenue generated from tobacco is one of the fundamental barriers to
      effective tobacco control in Pakistan. The tobacco control component of the
      National Action Plan for Non-Communicable Diseases Prevention, Control and Health
      Promotion in Pakistan (NAP-NCD) deems it critical to address this issue. A range
      of policy and environmental strategies are part of this comprehensive effort;
      these involve regulating access and limiting demand through restrictions on
      advertising, marketing, promotion and through price and taxation. The NAP-NCD
      also encompasses community and school interventions, enforcement of tobacco
      control policies, cessation programmes, mass media counter-marketing campaigns
      for both prevention and cessation, and surveillance and evaluation of efforts. As
      part of NAP-NCD, surveillance of tobacco use has been integrated with a
      population-based NCD surveillance system. Featuring tobacco prominently as part
      of an NCD behavioural change strategy and providing wide-ranging information
      relevant to all aspects of tobacco prevention and control and smoking cessation
      have been identified as priority area in NAP-NCD. Other priority areas include
      the gradual phasing out of all types of advertising and eventually a complete ban
      on advertising; allocation of resources for policy and operational research
      around tobacco and building capacity in the health system in support of tobacco
      control. NAP-NCD also stresses on the need to develop and enforce legislation on
      smuggling contrabands and counterfeiting and legislation to subject tobacco to
      stringent regulations governing pharmaceutical products. The adoption of measures
      to discourage tobacco cultivation and assist with crop diversification;
      integration of guidance on tobacco use cessation into health services and
      insuring the availability and access to nicotine replacement therapy are also
      part of NAP-NCD.

PMID- 15745326
TI  - Prevention and control of chronic chest diseases: National Action Plan for NCD
      Prevention, Control and Health Promotion in Pakistan.
AB  - The National Action Plan for Non-Communicable Disease Prevention, Control and
      Health Promotion in Pakistan (NAP-NCD) does not include surveillance of Chronic
      Respiratory Diseases (CRDs) into the integrated NCD surveillance model due to
      issues with assessing the magnitude of the burden of CRD in general and chronic
      obstructive pulmonary disease (COPD) in particular, within populations. Tobacco
      has been used as a proxy for the magnitude of COPD in the population. However, it
      stresses on the need to develop acceptable criteria for the diagnosis of CRDs and
      methodologies to monitor CRDs. The CRD component of the NAP-NCD integrates
      prevention of CRDs with a comprehensive NCD prevention and control framework with
      specific emphasis on tobacco as a cross-cutting theme. It prioritizes the
      examination of trends in outdoor air pollution levels and their determinants in
      order to develop appropriate public health interventions. Other priority areas
      include research to quantify the magnitude and determinants of chronic lung
      diseases attributable to indoor air pollution both in the rural and urban areas;
      the development of appropriate public health strategies to reduce risks in such
      settings and the integration of guidance on CRD prevention with an NCD behaviour
      change communication strategy. The cross-cutting theme of environmental pollution
      and occupational exposure to toxins develops common action areas for CRD and
      cancer prevention.

PMID- 15745327
TI  - Prevention and control of cancers: National Action Plan for NCD Prevention,
      Control and Health Promotion in Pakistan.
AB  - The National Action Plan for Non-communicable Diseases Prevention, Control and
      Health Promotion in Pakistan (NAP-NCD) integrates prevention and control of
      cancers with a comprehensive NCD prevention framework with a specific emphasis on
      tobacco, diet and physical activity as cross-cutting risks. The programme
      prioritizes on sustainable institutional support for mature cancer registries in
      order to facilitate cancer surveillance; prevention of cancers and early
      detection as part of an integrated NCD behavioural change communication strategy
      and building capacity in the health system for cancer prevention and control. The
      programme's research agenda also includes appropriate studies to bridge critical
      gaps in evidence relating to appropriate and cost-effective strategies for
      preventing common cancers in Pakistan. To contain exposure to carcinogenic agents
      in the environment and in worksites, NAP-NCD stresses on the transparent
      enforcement of National Environmental Quality Standards; the institution to take
      proactive measures to contain potential risks to cancers in industrial settings;
      stricter enforcement of labour laws, stringent regulations governing chemical
      handling and the active incorporation of preventive health in the mandate of
      organizations providing health coverage for the labour workforce. It has also
      been deemed essential to study cancer trends in defined industrial settings at
      high-risk and to identify causal associations in order to delineate precise
      targets for preventive interventions in the native setting. NAP-NCD stresses on
      the development of institutional mechanisms with a regulatory function for cancer
      control; these include a National Cancer Control Council, with the mandate to
      uphold ethics and principles and guidelines on technical matters and a National
      Occupational Safety and Health Association. The Plan also prioritizes on pain
      relief and palliative care alongside prevention and control efforts and stresses
      on the need to integrate prevention efforts into health services as a sustainable
      and evidence-based activity.

PMID- 15745328
TI  - Injury prevention and control: National Action Plan for NCD Prevention, Control
      and Health Promotion in Pakistan.
AB  - The National Action Plan for Non-communicable Disease Prevention, Control and
      Health Promotion in Pakistan (NAP-NCD) incorporates prevention of injuries into a
      comprehensive NCD prevention effort. This encompasses the prevention of road
      traffic crashes (RTC)s, occupational injuries, falls, burns and other injuries.
      In this programme, surveillance of injuries--as part of comprehensive population
      based NCD surveillance system, supplemented by multiple data sources--has been
      stipulated as an entry point, to injury prevention and control efforts. Actions
      areas for preventing RTCs include interventions to improve road safety education,
      identification and implementation of safety measures for traffic black-spots,
      enforcement of seatbelt and helmet laws and the development and implementation of
      highway ordinances. Recommendations have also been made to establish a road
      safety committee and to facilitate inter-sectoral action. It has also been deemed
      essential to enact and enforce legislation on locally manufactured vehicles,
      regulate drivers' training and licensing and evaluation of Highway Police Force
      from a performance and fiscal perspective. To prevent worksite injuries, a
      national consensus has been achieved to develop a comprehensive policy and to
      enact and enforce legislation for occupational health and safety; to include
      preventive health in the mandate of organizations dealing with worksite safety
      and to study patterns of occupational injuries and their determinants with a view
      to defining precise targets for preventive interventions. In addition NAP-NCD
      makes a strong case for the establishment of a National Safety Commission, the
      development of product safety standards for household usage, enforcement of
      legislation on building safety, and efforts to improve trauma care to the extent
      that a credible, cost-effective analysis suggests. It also calls for the need to
      formally evaluate interventions to reduce all forms of violence in Pakistan.
      Building capacity in the health system for injury prevention and building
      partnerships for sustainable outcomes in injury prevention have also been defined
      as priority areas.

PMID- 15745329
TI  - Prevention and control of mental illnesses and mental health: National Action
      Plan for NCD Prevention, Control and Health Promotion in Pakistan.
AB  - As part of the National Action Plan for Non-communicable Disease Prevention,
      Control and Health Promotion in Pakistan (NAP-NCD), mental illnesses have been
      grouped alongside non-communicable diseases (NCD) within a combined strategic
      framework in order to synchronize public health actions. The systematic approach
      for mental illnesses is centred on safeguarding the rights of the mentally ill,
      reducing stigma and discrimination, and de-institutionalisation and
      rehabilitation of the mentally ill in the community outlining roles of healthcare
      providers, the community, legislators and policy makers. The approach has
      implications for support functions in a number of areas including policy
      building, manpower and material development and research. Priority action areas
      for mental health as part of NAP-NCD include the integration of surveillance of
      mental illnesses in a comprehensive population-based NCD surveillance system;
      creating awareness about mental health as part of an integrated NCD behavioural
      change communication strategy; integration of mental health with primary
      healthcare; the development of sustainable public health infrastructure to
      support community mental health initiatives; building capacity of the health
      system in support of prevention and control activities; effective implementation
      of existing legislation and harmonizing working relationships with law enforcing
      agencies. NAP-NCD also stresses on the need to integrate mental health into
      health services as part of a sustainable and integrated medical education
      programme for all categories of healthcare providers and the availability of
      essential psychotropic drugs at all healthcare levels. It lays emphasis on
      protecting the interests of special groups such as prisoners, refugees and
      displaced persons, women, children and individuals with disabilities.
      Furthermore, it promotes need-based research for contemporary mental health
      issues.

PMID- 15745330
TI  - Integrated framework for action. National Action Plan for Prevention and Control
      of Non-communicable Diseases and Health Promotion in Pakistan.

PMID- 15745331
TI  - [Pianist's cramp and other musicians' diseases. Suddenly the body does not play
      its part].

PMID- 15745332
TI  - [Prof. E. Altmuller, Hannover, on frequent complaints of instrumentalists. Pain
      as permanent companion].

PMID- 15745333
TI  - [Effects on cognition and brain structure. Can musicians think better?].

PMID- 15745334
TI  - [Macroscopically inconspicuous finding in endoscopy. When nevertheless biopsy
      must be done?].

PMID- 15745335
TI  - [Coronary disease in women. More dangerous than breast cancer!].

PMID- 15745336
TI  - [A much promising trial with vaccine against HP viruses. Can a vaccination
      protect from cervix carcinoma?].

PMID- 15745337
TI  - [The era of the classical bacterial epidemics is over. Today the challenge is
      from the "Domestic Germs"].

PMID- 15745338
TI  - [Bacterial infections following injections and infusion caused by errors of
      hygiene--how to avoid them].
AB  - Even minor medical interventions, such as injections, are associated with the
      risk of life-threatening infections--both in the doctor's office and hospital
      settings. Medical personnel in particular must always assume that they may be
      contaminated by facultative pathogenic, but potentially highly virulent, germs,
      although they themselves remain asymptomatic. Against this background, hygienic
      hand disinfection and proper skin disinfection are important hygiene measures for
      the prevention of infections, in particular in the case of invasive
      interventions. Strict attention must be paid to asepsis when preparing for
      injections and infusions. Sterile items must be protected against contamination.
      With regard to compliance with and application of hygiene standards, every
      physician must be an exemplary role model. Furthermore, all medical professional
      groups must receive appropriate training in hygiene management.

PMID- 15745339
TI  - [Are we being threatened by multiresistant strains of Staphylococcus aureus?].
AB  - Multiresistant strains of Staphylococcus aureus (MRSA) are characterized by their
      virulence and clinical resistance to all known beta-lactam antibiotics.
      Furthermore, the representatives of most other classes of antibiotics are also
      proving to be no longer effective. While infections with the usual S. aureus
      strains can mostly be readily managed with penicillinase-resistant penicillins,
      the rescue antibiotic vancomycin, as also teicoplanin, in combination with, for
      example fosfomycin, are required in the treatment of MRSA and S. epidermidis
      infections. Since infections with S. aureus/MRSA are usually of endogenous
      origin, decolonization with mupirocin-containing nasal ointment applied as a
      prophylactic measure in patients with high colonization rates and/or
      immunosuppression, is of major importance. The best protection against further
      spread of highly resistant germs, such as MRSA is, in particular, profession
      hygiene management.

PMID- 15745340
TI  - [Bacterial infections of the lungs in mucoviscidosis patients].
AB  - The pathogenesis of lung infections in patients with mucoviscidosis (cystic
      fibrosis, CF) is multifactorial. Both host- and pathogen-related factors are
      involved. The most important germ in terms of progression and pulmonary damage is
      Pseudomonas aeruginosa. However, the clinical relevance of other CF-typical
      pathogens has not yet been determined with certainty, and must be assessed on the
      basis of the clinical presentation of the individual case. To ensure optimal
      patient management, a CF-specific microbiological diagnostic work-up is
      mandatory. Since ever more patients now survive into adulthood, the problems
      associated with chronic infection are gaining in importance. In light of
      increasing multiresistance, the use of inhalation antibiotics, as well as
      combined antibiotic treatment, is becoming more and more determinative for the
      therapeutic outcome.

PMID- 15745341
TI  - [Secretory activity of the adipocytes and comorbidities of obesity].
AB  - Fatty tissue synthesizes and secretes a wide range of products that may be
      directly involved in the pathogenesis of the complications associated with
      obesity. These so-called adipokines may trigger or sustain a chronic inflammatory
      process. By manipulating the secretory function of fat cells, it might in future
      be possible to prevent the development of the metabolic and cardiovascular
      complications of obesity. Current data already suggest that weight reduction and
      certain substances with an anti-inflammatory action reduce the risk for the
      metabolic and cardiovascular complications of obesity. To date, however, the
      evidence available is only indirect, and is insufficient to definitively
      establish causal relationships between certain secretory products of adipocytes
      and the comorbidities of adiposity. Further clinical studies are needed.

PMID- 15745342
TI  - [Gainfully employed despite a chronic illness. What occupations can still be
      carried out by a diabetic?].

PMID- 15745343
TI  - [Family physician model of MEDI physicians. Before hospitalization ask first the
      specialty physician].

PMID- 15745344
TI  - [More and more care models. How to deal with the new bureaucracy?].

PMID- 15745345
TI  - [Help fund created for those harmed by Ulla Schmidt. Family physicians collect
      donations for reform victims].

PMID- 15745346
TI  - [The 10-minute consultation. Accidental finding: hyperkalemia. Caution with
      analgesics and bananas].

PMID- 15745347
TI  - [Look diagnosis. Economy class syndrome after tractor driving].

PMID- 15745348
TI  - [Genes, environment and intelligence].

PMID- 15745349
TI  - [How to keep septic the patient alive?].

PMID- 15745350
TI  - [Dental caries is not gone].

PMID- 15745351
TI  - [Cancer is a souvenir from the RNA world].

PMID- 15745352
TI  - [Attention deficit hyperactivity disorder in adults].

PMID- 15745353
TI  - [Bile duct injuries during laparoscopic surgery--diagnosis and treatment].

PMID- 15745354
TI  - [Charles Bonnet's syndrome--visual hallucination of the visually impaired].

PMID- 15745355
TI  - [Genetic mutation as a risk factor for a patient treated with warfarin].

PMID- 15745356
TI  - [Acute myocardial infarction after snow removal].

PMID- 15745357
TI  - [Symptoms like watching old home movies].

PMID- 15745358
TI  - [Targeted cancer drugs and their development].

PMID- 15745359
TI  - [Comment on sociosomatics and other theories of medical care].

PMID- 15745360
TI  - [Is tissue typing is unnecessary for kidney transplantation?].

PMID- 15745361
TI  - [Response to a previous letter on tissue typing for kidney patients].

PMID- 15745362
TI  - [Outi Heiskanen: Doomed].

PMID- 15745363
TI  - [Palliative medicine].

PMID- 15745364
TI  - [Palliative care in local hospital].

PMID- 15745365
TI  - [Is there a need for end-of-life care in geriatrics?].

PMID- 15745366
TI  - [Is oral medication effective for treatment of pain?].

PMID- 15745367
TI  - [Palliative care tailored according to the symptoms of the ALS patient is an art
      form].

PMID- 15745368
TI  - [Burnout physicians working in palliative care].

PMID- 15745369
TI  - [Palliative care is on behalf of a good life].

PMID- 15745370
TI  - Eosinophils, specific hyperreactivity and occurrence of late phase reaction in
      allergic rhinitis.
AB  - BACKGROUND: Eosinophil infiltration may be considered characteristic of nasal
      allergic inflammation. However, a mild inflammatory infiltrate may be present in
      asymptomatic subjects exposed to specific allergen. OBJECTIVE: We investigated
      the relationship between inflammation, specific hyperreactivity and clinical late
      phase reactions in allergic subjects using the ASNC model. METHODS: Sixty
      allergic subjects (aged from 18 to 47 years) were enrolled among those sensitized
      to pollens (n=20) and those to house dust mite with (n=20) or without (n=20)
      known clinical nasal LPR. All subjects were asymptomatic. TNSS and eosinophil
      number were assessed at baseline, 30 min (early phase) and 6 hours (late phase)
      after ASNC. RESULTS: Eosinophil number was higher in LPR+ rhinitics than in other
      groups, at baseline and during the early and late phase (p<0.001). ATD was lower
      in LPR+ rhinitics than in other groups (p<0.001). In LPR+ rhinitics, at baseline
      there was a significant correlation between eosinophils and ATD (r=0.56,
      p=0.009). After allergen challenge, TNSS was significantly higher in LPR+
      rhinitics than in other groups, both during early and late phase (p<0.001 for all
      comparisons). CONCLUSIONS: In house dust mite sensitised subjects, LPR occurrence
      after allergen challenge is associated with higher inflammation and lower ATD at
      baseline. Therefore, in house dust mite allergy minimal persistent inflammation
      without symptoms can drive different clinical responses to allergen challenge.

PMID- 15745372
TI  - Solar urticaria and porphyrias.
AB  - The importance of disturbances of porphyrin metabolism in solar urticaria is
      discussed. 15 cases of porphyrias with sun sensitivity are presented comprising 5
      cases of erythropoietic protoporhyria, 8 cases of coproporphyria hereditaria and
      2 cases of porphyria variegata, 9 out of these 10 patients presented
      neuroabdominal symptoms and in 4 cases contraceptive pills have triggered the
      disease. Due to the risk of severe forms of disease sometimes drugs induced
      porphyrias must be considered in all cases of solar urticaria and a correct
      laboratory study done in the suspected cases.

PMID- 15745371
TI  - Air pollution and atopy.
AB  - Relationships between air pollutants and atopy can be studied within 3 different
      settings. In vitro, exposure of pollen to air pollutants induce morphological
      changes and seems to facilitate extrusion on allergenic material out of the
      pollen grain. In animal as well as in human experiments, air pollutants,
      especially diesel exhaust particulates, are able to trigger an IgE-response.
      Epidemiological surveys also show that air pollutants trigger symptoms in
      patients. In contrast, whether or not air pollutants can induce de novo allergic
      diseases is still a matter of debate. Some surveys suggest that, in humans also,
      air pollutants, especially diesel-exhaust particulates, could trigger allergic
      sensitization and development of atopic diseases. At home, other pollutants can
      be involved: volatile organic compounds have pro-inflammatory properties and
      favour T-cell sensitization. Relationship between exposure to secondhand tobacco
      smoke or occupational hazards and atopic sensitization have led to discordant
      results.

PMID- 15745373
TI  - Long-term follow-up of allergic conjunctivitis in children: the out-patients'
      department experience (allergic conjunctivitis in children: management and care).

PMID- 15745374
TI  - Levocetirizine improves nasal symptoms and airflow in patients with persistent
      allergic rhinitis: a pilot study.
AB  - BACKGROUND: Nasal obstruction is the main symptom in patients with persistent
      allergic rhinitis. Some antihistamines have been demonstrated to be capable of
      improving this symptom. The aim of this pilot study was to evaluate nasal
      symptoms, nasal airflow, and decongestent activity in patients with persistent
      allergic rhinitis, before and after treatment with levocetirizine or placebo.
      METHODS: Forty patients with persistent allergic rhinitis were evaluated, 35
      males and 5 females (mean age 23.3 +/- 5.9 years). All of them received
      levocetirizine (5 mg/daily) or placebo for 4 weeks. The study was double-blind,
      parallel-group, placebo-controlled, and randomized. Total symptom score
      (including: nasal itching, sneezing, rhinorrhea, and nasal obstruction) was
      assessed before and after treatment. Rhinomanometry and decongestion test were
      performed in all subjects before and after treatment. RESULTS: Levocetirizine
      treatment induced: significant symptom relief (p<0.001), improved nasal airflow
      (p<0.001), reduction of reversibility percentage (p<0.05), and increase of total
      airflow after decongestion test (p<0.03). Placebo did not improve nasal symptoms
      and airflow. CONCLUSIONS: This pilot study demonstrates the effectiveness of
      levocetirizine in: i) relieving nasal symptoms, including obstruction, ii)
      improving nasal airflow, and iii) exerting decongestant activity. Thus, these
      findings are the first evidence of the impact on airflow and the decongestant
      activity exerted by levocetirizine in persistent allergic rhinitis.

PMID- 15745375
TI  - Increased CD34+ cell peripheral traffic appears to be an unique feature of the
      allergic inflammation.
AB  - Evidence has been cumulated during the last years concerning the immaturity of
      the cells involved in the local and systemic aspects of allergic inflammation.
      Hematopoietic precursors (HPC) are mobilized from the bone matrix as multipotent
      cells or, more often, as progenitors that, after the initial white-lineage
      commitment reach through the peripheral blood (PB) their final destinations
      constituted by the target organs of allergy. Although several studies have
      investigated the CD34+ cells traffic and location at the level of the inflamed
      peripheral mucosae in allergic populations, limited information is available on
      their behaviour on the time-course of infectious diseases. The current study thus
      was designed to asses the peripheral traffic of CD34+ HPC during the infectious
      inflammation. To this end CD34+ HPCs have been enumerated, by flow-cytometric
      techniques, in PB of 24 adult healthy beings (Group A), 24 adult subjects with
      symptomatic extrinsic allergy (Group B) and in PB of 24 adult patients
      hospitalised for febrile infectious pathology (Group C). CD34+ cell values ranged
      0.01-0.08% with a median of 0.03 in Group A. In Group B values ranged 0.17-0.75%
      with a median of 0.28 and in Group C values ranged 0.00-0.12% with a median of
      0.07. Variance analysis test among the three groups was statistically significant
      (p<0.001) supporting the conclusion that CD34+ HPC mobilizing and increased
      peripheral traffic is an unique feature of the allergic inflammation.

PMID- 15745376
TI  - Anaphylaxis to sesame paste.
AB  - Anaphylaxis reaction to sesame paste could be a possible complication of
      vegetarian diet. This paper presents a case of a 6-year-old child who developed
      anaphylactic reaction after eating bread and sesame paste (obtained by grinding
      sesame seeds). The child suffered atopic dermatitis and had no incidence of
      anaphylaxis before. Because the sesame, as seeds, oil or paste is mostly used in
      bakery and in different foods, by non diagnosing this allergy in children with
      atopic dermatites could be life-threatening.

PMID- 15745377
TI  - [CME radiology 5. Productive cough].

PMID- 15745378
TI  - [The patient with slightly increased liver function tests].
AB  - The availability of serum blood chemistries for screening both symptomatic and
      asymptomatic patients has resulted in a marked increase in the number of abnormal
      liver chemistry tests that must be interpreted by physicians. Usually the first
      step in the evaluation of a patient with elevated liver enzymes is to repeat the
      test to confirm the result. If the result is still abnormal, it seems wise to
      differentiate between a predominant "necrotic pattern" of liver chemistry, as
      indicated by an elevation of ALT- or AST-activity or a predominant "cholestatic
      pattern", as indicated by elevated activities of g-GT and alkaline phosphatase.
      In patients with elevated serum amino transferases hepatic diseases should be
      excluded primarily with non-invasive serologic tests. The most common causes of
      elevated amino transferase levels are chronic hepatitis B and C,
      autoimmunhepatitis, non-alcoholic steatohepatitis, hemochromatosis, Wilson
      disease and (only recently recognized) celiac sprue. In the case of a dominant
      "cholestatic pattern", primary biliary cirrhosis, primary sclerosing cholangitis,
      but also drugs and granulomatose hepatitis must be excluded. If non-invasive
      serologic studies remain inconclusive, ultrasound, mini-laparoscopy and liver
      biopsy will help to establish the final diagnoses.

PMID- 15745379
TI  - [Inflammatory bowel disease--diagnosis and therapy].
AB  - The first intention in the management of patients with inflammatory bowel disease
      (IBD) is the improvement of quality of life. It is important to avoid unnecessary
      investigations and to protect the patients from therapeutic approaches, which
      efficacy is not proven. The following remarks are based on the guidelines of The
      German Society of Gastroenterology for diagnosis and therapy of ulcerative
      colitis and Crohn's disease, which include an accurate diagnosis, the treatment
      of the acute phase, the maintaining of remission and the management of
      complications. The therapy depends on the severity of the acute phase and on the
      localisation of the disease. Immunosuppressive therapy with azathioprine or
      mercaptopurine is indicated in patients with steroid-dependent or steroid
      resistant disease.

PMID- 15745380
TI  - [Arthrosis pain: a frequent problem. Paracetamol is the first choice according to
      EULAR recommendation].

PMID- 15745381
TI  - [Treatment, follow up and prevention of colorectal carcinoma: strategies and
      controversies in the year 2005].
AB  - Colorectal carcinomas are common, so efficient strategies in their prevention and
      treatment will significantly lower mortality. Life style changes are an efficient
      primary prevention, but mass screening of the population can reduce morbidity and
      mortality even further. Complete resection is the clue to cure in colorectal
      carcinomas. Total mesorectal excision and laparoscopic operations have been
      established as effective interventions that may also improve patients' quality of
      life. Adjuvant therapy reduces recurrence rates and is recommended in stage II
      and III rectal carcinoma and stage III colon carcinoma. The optimal strategies
      for adjuvant therapy are currently being redefined. The availability of new drugs
      has extended the therapeutic options in metastatic disease, improving response
      rates and overall survival in the palliative situation. Sequential therapies with
      different drug combinations seem to be the most effective strategy. The operative
      resection of localized metastases to the liver or lung can cure some patients
      with metastatic disease.

PMID- 15745382
TI  - [A 23-year old patient with chronic diarrhea. Celiac disease and lactose
      intolerance].

PMID- 15745383
TI  - [CME-ECG solution. Tibial fracture. WPW with posteroseptal accessory pathway].

PMID- 15745384
TI  - Therapeutic options for chronic obstructive pulmonary disease: present and
      future.
AB  - By 2020, chronic obstructive pulmonary disease (COPD) will become the third
      leading cause of mortality and fifth leading cause of disability worldwide.
      Although traditionally therapeutic nihilism has dominated the approach to the
      management of COPD patients, it is becoming increasingly clear that COPD is a
      highly preventable and treatable condition. Smoking cessation is the most
      important therapy because it is the only intervention that has been shown to
      modify the accelerated decline in lung function that is characteristic of COPD.
      Domiciliary oxygen therapy for those who are hypoxemic at rest results in
      improved survival. Vaccinations and immunizations against influenza and
      pneumococcus should be encouraged. Bronchodilators are used for symptomatic
      relief. Recent introduction of long-acting bronchodilators facilitates good
      control of dyspnea with once or twice daily dosing. In conjunction with inhaled
      corticosteroids, they appear to produce added clinical benefits. Pulmonary
      rehabilitation and lung transplantation are other therapeutic options for select
      groups of patients. Many promising compounds are in various stages of development
      as future therapies in COPD. Drugs such as phosphodiesterase 4 inhibitors,
      tyrosine kinase blockers and peroxisome proliferator-activated gamma receptor
      agonists show great promise as disease-modifying agents in COPD.

PMID- 15745385
TI  - Early protective effects of tiotropium bromide in patients with airways
      hyperresponsiveness.
AB  - Tiotropium is an anticholinergic drug for Chronic Obstructive Pulmonary Disease
      (COPD) patients, with a peak bronchodilator effect observed after 1.5 to 2 hours
      and a long duration of action. The aim of our study was to quantify the early
      protection of a single dose of inhaled tiotropium against methacholine-induced
      bronchoconstriction in asthmatic patients with airway hyperresponsiveness. Ten
      subjects (7M, 3F), with history of asthma and a baseline FEV(1) (Forced
      Expiratory Volume 1 sec) > 80% of predicted, were enrolled in the study. Each
      subject performed three methacholine challenge tests, with a time of 72 hours
      between each challenge: Test A (methacholine challenge test), and successively,
      at random, Test B (methacholine 30 minutes after inhaled Tiotropium) and Test C
      (methacholine 30 minutes after inhaled Placebo). PD20 (Provocative Dose causing a
      20% decrease in basal FEV(1) value) was reached to assess airways responsiveness.
      All the subjects showed in Test A and Test C a mild-moderate airway
      hyperresponsiveness. In Test B no PD20 was reached at the inhaled maximum dose of
      methacholine (1600 microg), FEV(1) before tiotropium was 88.6% +/- 4.4, beginning
      test FEV(1) 92.6% +/- 4.3, end test FEV(1) 85.7% +/- 4.6. Inhaled tiotropium
      bromide 18 microg has shown a protective effect against methacholine-induced
      bronchoconstriction in asthmatic patients, with mild-moderate airways
      hyperresponsiveness, already 30 minutes after its administration.

PMID- 15745386
TI  - Spinal metastases: treatment evaluation algorithm.
AB  - Spinal metastases are only apparently similar lesions, considering the large
      varieties of istotypes and the spread of the primary tumor. These metastases
      develop early and are not terminal events, they have to be considered as severe
      complications because, when possible, surgical treatment can improve the history
      of the patient in terms of life expectancy and quality of life. The approach to
      these lesions should be multidisciplinary in collaboration with oncologists and
      radiotherapists, in fact the average of survival of these patients has increased
      in recent years. The evolution of anesthaesiological techniques that permit
      surgical treatments that were once considered prohibitive. The application of new
      adjuvant therapy increases the effectiveness for surgical treatment. Controversy
      exist over the most appropriate treatment for patients with metastatic disease of
      the vertebral column. The purpose of this article was to determine the best
      sequential process to arrive at the most appropriate treatment considering the
      individual general conditions and the parameters of the metastases. We review 269
      cases in 182 patients suffering from spinal metastases from a solid tumour
      treated between 1996 and 2002. As the number of treatment options for metastatic
      spinal disease has grown, it has become clear that effective implementation of
      these treatments can only be achieved by multidisciplinary approach.

PMID- 15745387
TI  - Fabry disease with special reference to neurological manifestations.
AB  - Fabry's disease is an X-linked recessive Lysosomal Storage disease. The
      underlying metabolic defect is deficiency of lysosomal enzyme
      ceramidetrihexosidase. The disease has multisystem involvement. Neurological
      manifestations include small-fiber polyneuropathy manifested as painful distal
      extremities and anhidrosis. Fabry's disease also presents with both small-vessel
      and cortical multiple cerebral infarcts. Enzyme-replacement therapy has been
      found effective but expensive. Gene therapy could evolve as the ultimate
      therapeutic strategy.

PMID- 15745388
TI  - Does rifaximin prevent complications of diverticular disease? A retrospective
      study.
AB  - While the treatment of complicated diverticular disease (DD) is standardized, the
      approach to the symptomatic DD and prevention of relapsing complicated DD is
      still debated. An open question is whether nonabsorbable antibiotics may reduce
      the incidence of major complications of DD. We wanted to retrospectively analyze
      the prevalence of this disease in a large population of patients undergoing
      colonoscopy in our center in the last 10 years. Patients with symptomatic or
      complicated DD were treated with rifaximin 1,200 mg/die for 10-12 days during the
      acute phase in addition to the appropriate systemic antibiotics, followed by a
      prophylactic regimen with 800 mg/die for 7 days every month. The patients were
      followed up to December 2003, and the incidence of new complications and the
      relapses of symptomatology were determined. A total of 11,344 patients were
      screened. Of them, 2,287 showed an anatomical diverticulosis, and 408 had a
      diagnosis of complicated DD. The results indicate that the prevalence of DD-
      either in the uncomplicated or complicated form--in our area (Abruzzo, Italy) is
      identical to that of European countries, whose diet is characterized by a low
      amount of fiber and a high content of calories and refined sugars. Along a period
      of 10 years, a relapsing symptomatology of DD was observed in 112 patients
      treated with rifaximin (4.89%), while new complications of the DD were observed
      in 27 patients (1.18%). The comparison of these data with those of larger
      published series suggests a possible role of rifaximin in the prevention of DD
      main complications.

PMID- 15745389
TI  - Epidemiology of alternaria alternata allergy: a prospective study in 6840 Italian
      asthmatic children.
AB  - BACKGROUND: The prevalence of Alternaria Alternata (AA), a mold causing in
      children severe asthma is scarcely known, also due to the underdiagnosis of AA
      allergy, frequently due to multiple sensitizations to molds. OBJECTIVE: To
      analyze this issue we prospectively studied all children attending our Division
      between January 4, 1990 and December 31, 1997. METHODS: A total of 6840 children
      with asthma or allergic rhinitis were evaluated. Diagnosis was established by
      family and personal history, physical examination, skin prick tests (SPTs) and
      RAST (Radio Allergo-Sorbent Test) for inhalants including AA. We further
      evaluated: (1) sensitization only to AA allergens without positivity for
      additional inhalants; (2) prevalence of AA positivity among children with asthma
      or allergic rhinitis; (3) concordance between SPTs and RAST for allergy to molds,
      (4) proportion of children treated with specific immunotherapy (SIT). RESULTS:
      Among the 6840 children 213 were positive to AA (3.3%), only 89/6840 children
      (1.3%) had AA monosensitization (p = 0.0001), a concordance between SPTs and RAST
      was present in 21/89 (23.6%) children (p = 0.0009), and only 9 children out of 89
      were SIT treated. Concerning the clinical manifestations, 83 had asthma or
      allergic rhinitis, and 6 had asthma associated with atopic dermatitis. Family
      history was positive in 82.9% of children. The mean onset of AA sensitivity was
      at age 4 for males, and at age 5 for females. CONCLUSIONS: In childhood, AA
      allergy is a genetic affection. The SPT concordance with history and clinical
      examination appears to be operative. Due to life-threatening reactions in
      children with AA allergy, we suggest that those with suspected inhalant allergy
      be tested with AA allergens, and treated with SIT if positive.

PMID- 15745390
TI  - Gastric emptying time in cyclic vomiting syndrome in children.
AB  - Pathogenesis of cyclic vomiting syndrome (CVS) is still uncertain. Aim of our
      study has been to verify the role of gastric emptying time in children affected
      by CVS. We studied 9 children with CVS who underwent measurement of gastric
      emptying time by real-time ultrasonography after administration of a mixed, solid
      liquid meal. In all the children gastric emptying time resulted in normal range.
      Our data suggest that mobility abnormalities of the stomach don't play a key role
      in the pathogenesis of CVS.

PMID- 15745391
TI  - Invasive pneumococcal disease in Australia, 2003.
AB  - There were 2,174 cases of invasive pneumococcal disease (IPD) notified to the
      National Notifiable Diseases Surveillance System (NNDSS) in Australia in 2003; a
      rate of 10.9 per 100,000 population. The notification rate varied between states
      and territories and by geographical region with the highest rates in the north of
      the country. Invasive pneumococcal disease was reported most frequently in
      children aged less than two years (98.8 cases per 100,000 population). Enhanced
      surveillance for IPD in 2003 was carried out in all states and territories,
      providing additional data on 1,842 (85%) of all notified cases. Rates of IPD in
      Indigenous Australians were three times the rate in non-Indigenous Australians.
      There were 125 deaths attributed to IPD resulting in an overall case fatality
      rate of 6.8 per cent. Seventy-one percent of all pneumococcal isolates serotyped
      were serotypes in the seven-valent conjugate vaccine and 91 per cent were
      serotypes in the 23-valent polysaccharide pneumococcal vaccine. The clinical
      presentation and risk factors for IPD varied between Indigenous and non
      Indigenous cases and non-vaccine serotypes occurred more frequently among
      Indigenous children and adults. Data from three years of surveillance indicate an
      early impact of the 7-valent vaccine in the target population.

PMID- 15745392
TI  - Laboratory surveillance of invasive pneumococcal disease in Australia, 2003
      predicting the future impact of the universal childhood conjugate vaccine
      program.
AB  - A comprehensive invasive pneumococcal disease (IPD) laboratory surveillance
      program was carried out in Australia in 2003. This program provided data on the
      prevalence of pneumococcal serotypes and antimicrobial resistance. There were
      1,995 isolates tested with 34 per cent (683) from children aged less than five
      years and 27 per cent (535) from the elderly aged more than 65 years. One
      thousand eight hundred and sixty were isolates from blood, 79 from CSF and 56
      from other sterile sites. In young children, 84 per cent of isolates were a
      serotype and 92 per cent a serogroup in the 7-valent pneumococcal conjugate
      vaccine (7vPCV). Of penicillin resistant isolates in children less than five
      years of age 85 per cent and 98 per cent were a serotype and serogroup in the
      7vPCV respectively. When the universal 7vPCV vaccine program in young children is
      introduced in 2005, a proportion of cases of IPD should also be prevented in
      young adults (estimated reduction of 54 cases annually) and elderly Australians
      (an estimated reduction of 110 cases annually) as a result of improved herd
      immunity. Pneumococcal serotypes with higher rates of penicillin resistance (19F,
      14 and 6B) were more prevalent in the elderly than in young children. In
      contrast, erythromycin resistance was more common in children less than five
      years of age (24%) compared to the elderly (15%). The predominant serotype with
      erythromycin resistance in Australia was serotype 14 and thus there is likely to
      be a major reduction in erythromycin resistance as a result of 7vPCV vaccination.
      Continued surveillance of pneumococcal serotype distribution and antibiotic
      susceptibility will be essential in order to identify serotype replacement by non
      vaccine serotypes and to monitor the overall impact of current and future vaccine
      programs on invasive pneumococcal disease in Australia, not only in young
      children but also in other age groups.

PMID- 15745393
TI  - Tuberculosis notifications in Australia, 2003.
AB  - The National Notifiable Disease Surveillance System (NNDSS) received 982
      tuberculosis (TB) notifications in 2003, of which 947 were new cases, 33 were
      relapses and two were cases with unknown history. The incidence of TB in
      Australia has remained at a stable rate since 1985 and was 4.9 cases per 100,000
      population in 2003. The high-incidence groups remain people born overseas and
      Indigenous Australians at 19.9 and 8.7 cases per 100,000 population,
      respectively. By contrast the incidence in non-Indigenous Australians was 0.9 per
      100,000. Comparison of the 2003 TB notification data against the performance
      indicators set by National Tuberculosis Advisory Committee highlights that
      enhanced TB control measures should be considered among these high-risk groups.

PMID- 15745394
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      2003. A report of the Australian Mycobacterium Reference Laboratory Network.
AB  - The Australian Mycobacterium Reference Laboratory Network collected and analysed
      laboratory data on new cases of disease caused by Mycobacterium tuberculosis
      complex in the year 2003. A total of 784 cases were identified by bacteriology,
      representing an annual reporting rate of 3.9 cases of laboratory confirmed
      tuberculosis per 100,000 population. The most commonly encountered culture
      positive specimens were sputum (n = 351), lymph node (n = 176) and from
      bronchoscopy (n = 97). Smears containing acid fast bacilli were present in sputum
      (53.0%), bronchoscopy (32.0%) and lymph node (23.3%). Five children (female n =
      3, male n = 2) under 10 years of age had bacteriologically confirmed
      tuberculosis. Eighty isolates of M. tuberculosis and one of Mycobacterium
      africanum (10.3%) were resistant to at least one of the standard anti
      tuberculosis agents. Mono-resistance to isoniazid, ethambutol, rifampicin, and
      pyrazinamide was detected in 45, three, two, and one isolates respectively.
      Multidrug-resistance (MDRTB) defined as resistance to both isoniazid and
      rifampcin was observed in seven (0.9%) isolates. Of the seven MDRTB isolates, six
      were from the respiratory tract and four were from smear positive specimens. Of
      the 81 patients with drug resistant isolates, 78 (96.3%) were classified as
      having initial resistance; two had acquired resistance and no information was
      available for one isolate; five were Australian-born; and 76 (93.8%) had migrated
      from a total of 30 countries.

PMID- 15745395
TI  - Report of the Australian Rotavirus Surveillance Program 2003-2004.
AB  - The National Rotavirus Reference Centre together with collaborating laboratories
      Australia-wide has conducted rotavirus surveillance since June 1999. This report
      describes the serotypes of rotavirus strains responsible for the hospitalisation
      of children with acute gastroenteritis during the period 1 July 2003 to 30 June
      2004. We examined 688 faecal samples using monoclonal antibody immunoassays,
      reverse transcription-polymerase chain reaction and polyacrylamide gel analysis.
      This revealed that serotype G1 has re-emerged as the major serotype nationally,
      representing 40 per cent of all strains, followed by serotype G3 (25.7%) serotype
      G2 (17.1%) and serotype G9 (11.7%). However, there is substantial geographic
      variation in the prevalence of rotavirus serotypes. These findings have
      implications for vaccine development strategies which have targeted prevention of
      disease due to serotypes G1-G4.

PMID- 15745396
TI  - A report from the Communicable Diseases Network Australia, July to September
      2004.
AB  - The Communicable Diseases Network Australia (CDNA) consists of communicable
      disease authorities from various Australian Government agencies and state and
      territory health authorities, in addition to expert bodies and individuals in the
      specific areas of communicable disease epidemiology, clinical management, disease
      control and laboratory diagnosis. The CDNA provides national public health
      leadership and co-ordination on communicable disease surveillance, prevention and
      control, and offers strategic advice to governments and other key bodies on
      public health actions to minimise the impact of communicable diseases in
      Australia and the region.

PMID- 15745397
TI  - The acceptance of three simultaneous vaccine injections recommended at 12 months
      of age.
AB  - Since January 2003, vaccination with Meningococcal C conjugate vaccine (MenCCV)
      is recommended at 12 months of age, at the same time as the measles-mumps-rubella
      (MMR) and Haemophilus influenzae type b (Hib) vaccines. Most (83%) of a cohort of
      751 children in north Queensland born in January 2003 received the three
      injectable vaccines simultaneously. Of the 122 children who had not received
      MenCCV with the other two vaccines, 88 (72%) had received it by 18 months of age.
      The median age of receipt of MenCCV in the children who had received the three
      vaccines simultaneously was 12.3 months, whereas the median age in the children
      who had not received it at the same time as the other two vaccines was 14.0
      months. This study suggests that non-simultaneous vaccination puts children at
      risk of receiving MenCCV late, or not at all, and has implications for the
      introduction of universal infant pneumococcal vaccination program, starting in
      January 2005.

PMID- 15745398
TI  - A family cluster of serogroup C meningococcal disease.

PMID- 15745399
TI  - Top end rural and remote Indigenous women: an Australian population group
      vulnerable to rubella.
AB  - Australian efforts to prevent cases of congenital rubella syndrome have been
      largely successful, although concerns that eradication has not yet been achieved
      are ongoing. This paper describes an Australian population group with a
      vulnerability to rubella which has not previously been reported. Fewer than 75
      per cent of Indigenous women from rural and remote communities who gave birth at
      Royal Darwin Hospital in 1999 and were tested for rubella antenatally had
      adequate levels of immunity. By comparison Indigenous and non-Indigenous women
      living in the Darwin urban area had a prevalence of adequate immunity to rubella
      on antenatal testing of > 90 per cent, similar to estimates for other Australian
      born population groups. Action is required to reduce the risk of cases of
      congenital rubella syndrome occurring in rural and remote Indigenous communities
      in the Top End, and may be needed in rural and remote settings elsewhere in
      Australia. Ensuring each child, adolescent and young adult has received two doses
      of Measles Mumps Rubella vaccine as part of their primary immunization course
      will provide increased protection. In addition, more women lacking adequate
      rubella immunity need to be vaccinated postnatally than was found in this study.
      Providers of women's care would be assisted in this task if laboratories adopted
      a standardized approach to reporting the results of antenatal rubella serology
      tests.

PMID- 15745401
TI  - The cost of seasonal respiratory illnesses in Australian children: the dominance
      of patient and family costs and implications for vaccine use.
AB  - Respiratory viral infections are one of the next group of diseases likely to be
      targeted for prevention in childhood by the use of vaccines. To begin collecting
      necessary epidemiology and cost information about the illnesses caused by these
      viruses, we conducted a prospective cohort study in 118 Melbourne children
      between 12 and 71 months of age during winter and spring 2001. We were interested
      in calculating an average cost per episode of community-managed acute respiratory
      disease, in identifying the key cost drivers of such illness, and to identify the
      proportion of costs borne by the patient and family. There were 202 community
      managed influenza-like illnesses identified between July and December 2001,
      generating 89 general practitioner visits, and 42 antibiotic prescriptions. The
      average cost of community-managed episodes (without hospitalisation) was dollar
      241 (95% CI dollar 191 to dollar 291), with the key cost drivers being carer time
      away from usual activities caring for the ill child (70% of costs), use of non
      prescription medications (5.4%), and general practice visits (5.0%). The patient
      and family met 87 per cent of total costs. The lowest average cost occurred in
      households from the highest income bracket. Acute respiratory illness managed in
      the community is common, with the responsibility for meeting the cost of episodes
      predominantly borne by the patient and family in the form of lost productivity.
      These findings have implications for preventive strategies in children, such as
      the individual use of, or implementation of public programs using, currently
      available vaccines against influenza and vaccines under development against other
      viral respiratory pathogens.

PMID- 15745400
TI  - Influenza A associated morbidity and mortality in a Paediatric Intensive Care
      Unit.
AB  - This paper reports the clinical features and outcome of all children with a
      laboratory proven diagnosis of influenza A virus infection admitted to a major
      Paediatric Intensive Care Unit (PICU) in 2003. Eight of the 22 patients with
      influenza A virus infection (A/Fujian/411/2002-like type) presented with
      encephalopathy and three of the 22 patients died. This can be compared with 44
      admissions and seven (16%) deaths of patients with influenza virus admitted in
      the same PICU in the preceding 15 years. In the present cohort, four (18%) of the
      22 patients, including one child who died, should have received influenza vaccine
      according to the current Australian immunisation recommendations. We have no
      documented evidence that any of the 22 children received influenza vaccination.
      During the 2003 influenza season there was an increased number of children
      admitted to our PICU with influenza A infection and an increased number of deaths
      compared with previous years. Influenza infection causes significant morbidity
      and mortality in young children, most of whom are not currently recommended for
      annual influenza vaccination.

PMID- 15745402
TI  - Hepatitis C prevalence--a nationwide serosurvey.
AB  - Hepatitis C is the most commonly notified disease in Australia. In 1998 the
      Hepatitis C Virus Projections Working Group (HCPWG) estimated that there were
      approximately 210,000 people who had been infected by hepatitis C virus (HCV) in
      Australia by 2001. Population-based serosurveys are required to validate this
      estimate. Here we estimate HCV prevalence on the basis of HCV antibody
      seroprevalence in the Australian national serosurvey. Between 1996 and 1998,
      2,800 sera opportunistically collected from pathology laboratories throughout
      Australia were tested for HCV antibody. National HCV notifications reported from
      1991 through 1998 were also assessed. Eighty-one sera were HCV antibody positive,
      giving an age standardised prevalence of 2.3 per cent (95% CI 1.8%-2.9%). The 20
      24 year age group had the highest HCV prevalence, 5.3 per cent (95% CI 3.3%-8.1%)
      and the male to female ratio was 1.8:1.0. Approximately 111,000 HCV notifications
      were received from 1991 through 1998. HCV prevalence estimated by the serosurvey
      is approximately three times higher than cumulative HCV notifications. Age and
      sex distributions of seroprevalence are broadly consistent with cumulative
      notification data. These distributions are consistent with the majority of HCV
      infections in Australia being transmitted by injecting drug use. Very low age
      specific seroprevalence estimates in the over 50 years age group indicate that
      there is not a large pool of undiagnosed infection in this age group. The
      serosurvey provides an estimate of Australian HCV prevalence and baseline data to
      determine incidence trends, both of which are required for health-care planning.

PMID- 15745403
TI  - A multi-jurisdictional outbreak of hepatitis A related to a youth camp-
      implications for catering operations and mass gatherings.
AB  - In June 2003, Australian state and territory health departments were notified of
      an outbreak of Hepatitis A in people who had attended a five-day youth camp.
      Approximately 350 people attended the event in Central Australia between 24 and
      28 April 2003. The public health investigation comprised of case identification,
      food handler interviews, an environmental health investigation of the campground
      and associated food premises, laboratory analysis of blood specimens and
      food/water samples, and an epidemiological study. Twenty-one cases fitted the
      case definition for the outbreak. A retrospective cohort study involving four
      states was conducted, with 213 people interviewed. Coleslaw and cordial were
      significantly associated with illness, however when the two exposures were
      adjusted for each other to account for confounding, only coleslaw remained
      significantly associated with illness (adjusted RR 2.5, 95% CI 1.09 - 5.77). The
      investigation highlighted a number of food hygiene and safety issues relating to
      the catering of mass gatherings. Implementation of food safety programs in these
      settings are likely to reduce the occurrence of such outbreaks. The recent
      proposal by Food Standards Australia New Zealand to mandate food safety programs
      for catering operations is supported.

PMID- 15745404
TI  - Outbreak of Salmonella Singapore associated with eating sushi.

PMID- 15745405
TI  - Reporting of communicable disease conditions under surveillance by the APSU, 1
      January to 30 June 2004.

PMID- 15745406
TI  - [Congenital cataract--the growth of the eyeball after the PC IOL implantation].
AB  - The authors followed the influence of PC IOL (posterior chamber intraocular lens)
      implantation in congenital cataract to the growth of the eyeball (six bilateral
      cataracts and 6 monolateral cataracts). The development of the eye growth was
      compared to the 6 healthy eyes of patients of this group. The intraocular lens
      implantation was performed at the age of 1 to 5.5 year, in average at the age of
      3 years. The follow up period was 4 to 7 years, mean 6 years. In operated, as
      well as in non-operated eyes, an equal average growth of the eyeball 0.2 mm per
      year was detected. All operated eyes were slightly hypermetropized according to
      the physiological values of growth of healthy eyes. The absolute mean deviation
      from emmetropia was 1.8 diopters. The author established the suitability of
      intraocular lens implantation in small children because of positive influence to
      the growth as well as to the final visual acuity, which ranged from 0.05 to 1.0,
      mean 0.4.

PMID- 15745407
TI  - [Visual functions in optic neuritis].
AB  - The authors present results of retrospective study of 25 patients with the first
      attack of acute optic neuritis followed at the Department of Ophthalmology,
      University Hospital Hradec Kralove. Visual functions were deteriorated in all
      patients. Visual acuity was in range between 0.8 to hand movement. Central
      scotoma was present in 12 patients, other visual field patterns were seen in 13
      patients. Complete recovery of visual functions was observed in 24 patients
      during the six months. Patients were examined for signs of multiple sclerosis
      (MS). In the group without MS (15 patients) were three treated with steroids (2
      received intravenous methylprednisolone and 1 oral prednisone before referral to
      us), vitamins were administered to the others. The patients with proved MS were
      managed at the Department of Neurology, University Hospital, Hradec Kralove.

PMID- 15745408
TI  - [Structural analysis of the optic nerve head in healthy eyes and in eyes with
      glaucoma].
AB  - PURPOSE: Assess the possibilities of structural analysis of the optic nerve head
      by Heidelberg Retina Tomograph (HRT) and its use in detection of glaucomatous
      changes of the optic nerve in particular. Indicate the topographical parameters
      that are most influenced by glaucoma and are therefore vital in early diagnosis
      of glaucomatous changes of the optic nerve. PATIENTS AND METHODS: Laser scanning
      tomography (HRT II) was used to examine 68 healthy eyes (control group) and 42
      eyes with open angle glaucoma (study group). All the examined subjects were older
      than 35 years of age. The analysis concerned the following topographical
      parameters of the optic nerve head: disc area, cup area and rim area, cup volume,
      rim volume, cup/disc area ratio, mean cup depth, maximum cup depth, mean retinal
      nerve fiber layer thickness (RNFL), RNFL cross sectional area, height variation
      contour and cup shape measure and discriminant functions used for classification
      of the optic nerve head finding according to F. S. Mikelberg and R. Burk.
      Statistical analysis was employed to ascertain the significant difference in
      these topographical parameters for the healthy eyes and the eyes with glaucoma.
      This method was used for both the whole optic disc and the 6 sectors of the optic
      nerve head. Another aim of the analysis was also to find out the correlation
      between the topographical parameters and age. RESULTS: Significant difference in
      the topographical parameters for the whole optic disc was spotted in the
      following parameters: rim volume, mean RNFL thickness, RNFL cross sectional area
      and discriminant function FSM. Significant differences were also found in between
      individual sectors of the optic nerve head, except for the upper temporal and
      upper nasal sector. The parameter, which varied most frequently between the
      groups, was rim volume. Significant correlations between age and topographical
      parameters were found for the following parameters: rim area, cup shape measure
      and mean RNFL thickness. CONCLUSION: Results of our study showed, that HRT is
      able to distinguish between normal and the pathological findings of optic nerve
      head according to topographical parameters significantly different between the
      two examined groups. These parameters are important in the diagnosis of glaucoma
      and also in the follow-up of patients with open angle glaucoma.

PMID- 15745409
TI  - [TNM classification of malignant ocular tumors].
AB  - The article presents contemporary TNM classification of malignant ocular tumors.
      This classification allows to establish the prognosis of the disease correctly
      and to choose proper treatment strategy. According to this classification, it is
      possible to compare results of the treatment and to communicate with the doctors
      and hospitals at the national and international level as well. It is necessary to
      acquaint the doctors especially in postgraduate courses with this classification,
      although the malignant ocular tumors represent only 0.2-0.5% of all tumors.

PMID- 15745410
TI  - [Posterior scleritis--a case report].
AB  - Authors present clinical manifestation and therapeutic possibilities in posterior
      scleritis, a disease, which may cause diagnostic dilemma. They also give an
      account of new examination methods which amend the diagnostic schema and safely
      confirm this diagnosis. In the article, a disease of a seventeen years old man is
      presented, in which posterior scleritis of unknown etiology was diagnosed.
      Following the systemic corticosteroid treatment the visual acuity of the affected
      eye improved, subjective signs disappeared, and the clinical manifestation
      returned to normal.

PMID- 15745411
TI  - [Siccaprotect eye drop--results of treatment in clinical practice].
AB  - The authors introduce Siccaprotect drops, a product of Ursapharm Ltd., and
      evaluate its efficiency on group of 91 patients suffering from the "Dry Eye"
      syndrome, in the period from 1. 9. 2003 to 30. 4. 2004. They report high
      effectiveness of Siccaprotect eye drops, particularly in those cases of dry eye
      syndrome, where support of epithelization is needed, irrespective of origin of
      the epithelial microdefects, together with dissolvance of non-infectious
      inflammation.

PMID- 15745412
TI  - Aspirin inhibits oculo-tensin and prevents rise of eye tension.

PMID- 15745413
TI  - Ocular changes following cataract extraction.

PMID- 15745414
TI  - Ciliary synechia.

PMID- 15745415
TI  - Optic atrophy (review of 100 cases).

PMID- 15745416
TI  - Bilateral orbital involvement in multiple myelomatosis.

PMID- 15745417
TI  - Pedunculated haemangioma from the conjunctiva.

PMID- 15745418
TI  - Developmental glaucoma and branch vein occlusion in thee retina.

PMID- 15745419
TI  - Antigens recognized by autologous antibodies of patients with soft tissue
      sarcoma.
AB  - Serological analysis of recombinant cDNA libraries (SEREX) uses high titer IgGs
      to identify antigens expressed by autologous cancers. In order to identify tumor
      antigens in soft tissue sarcoma (STS), sera from four patients with malignant
      fibrous histiocytoma (MFH), gastrointestinal stromal tumor (GIST), pleomorphic
      liposarcoma, and dedifferentiated liposarcoma were screened against cDNA
      libraries derived from autologous tumor. We identified 18 antigens encoded by 15
      different genes, including DLG7, which is located on chromosome 14q22, a locus
      previously found to be altered in STS, and the proto-oncogene JUN. Ten of
      fourteen antigens (71%) do not react with sera from healthy donors, suggesting
      that antibody recognition takes place during cancer progression. Using
      oligonucleotide microarray technology, most genes were variably expressed across
      a panel of 16 benign specimens and 41 STSs of different histologies. DLG7,
      however, showed restricted expression in testes and cancer, similarly to known
      germ cell cancer-testis antigens (or germ cell antigens, GCAs). Thus, the current
      study identified several antigens, including molecules implicated in
      tumorigenesis that were recognized by high titer IgGs in STS patients. Further
      studies of these selected novel STS antigens are warranted to identify and
      characterize potential antigen targets expressed by STS.

PMID- 15745420
TI  - Effects of short- and long-term ultraviolet B irradiation on the immune system of
      the common carp (Cyprinus carpio).
AB  - Carp (Cyprinus carpio) were repeatedly exposed to 0, 60, 120 and 240 mJ/cm2
      ultraviolet B (UVB) radiation three times in 1 week (short-term exposure) or 12
      times in 4 weeks (long-term exposure). The effect of UVB on the functioning of
      the carp immune system was studied on day 2 after the final irradiation. After
      short-term UVB exposure, the whole-blood respiratory burst and cytotoxic activity
      were markedly enhanced, with parallel responses in both the number of circulating
      granulocytes and in the plasma cortisol concentration of the fish. These changes
      were not detectable after long-term exposure. The respiratory burst by head
      kidney granulocytes was suppressed dose dependently after both exposures, but
      cytotoxic activity was not affected. Exposure to UVB also modulated lymphocyte
      functions: nonstimulated and PHA-stimulated proliferation of head kidney
      lymphocytes in vitro was enhanced by both short-term and long-term exposure. LPS
      stimulated proliferation was not affected by exposure nor was the number of
      immunoglobulin-secreting cells in the head kidney. In long-term exposure, the
      highest dose reduced the level of plasma IgM. This study indicates that UVB
      irradiation induces immunomodulation in the blood and head kidney of the carp and
      that the effects of short- and long-term exposure differ from each other. The
      results emphasize the potentially harmful impact of increased solar UVB radiation
      on fish immune functions.

PMID- 15745421
TI  - Topical application of a novel, water-soluble gamma-tocopherol derivative
      prevents UV-induced skin damage in mice.
AB  - We investigated whether the topical application of a novel, water-soluble gamma
      tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N-dimethylglycinate
      hydrochloride (gamma-TDMG), could protect against UV-induced skin damage in
      hairless mice. Topical pre- or post-application of a 5% (93 mM) gamma-TDMG
      solution in water/propylene glycol/ethanol (2:1:2) significantly prevented
      sunburn cell formation, lipid peroxidation and edema/inflammation that were
      induced by exposure to a single dose of UV irradiation of 5 kJ/m2 (290-380 nm,
      maximum 312 nm). This effect was greater than that seen with two alpha-Toc
      derivatives, alpha-tocopherol acetate (alpha-TA) and alpha-tocopherol-N,N
      dimethylglycinate (alpha-TDMG). When a 5% solution of gamma-TDMG was applied to
      mouse skin for 1 h, cutaneous gamma-Toc increased by 25-fold after 24 h; levels
      of cutaneous alpha-Toc increased by only two- and eight-fold in alpha-TDMG and
      alpha-TA treated skins, respectively. These findings indicated that gamma-TDMG
      immediately converted to gamma-Toc in the skin and suggest that ability of gamma
      TDMG to protect the skin from the damaging effects of irradiation was due to its
      conversion to gamma-Toc. When a 5% solution of gamma-Toc was applied to mouse
      skin for 1 h, cutaneous gamma-Toc rapidly increased by 25-fold, but fell to
      baseline levels by 24 h. In contrast, the concentration of gamma-Toc in skin that
      was treated with gamma-TDMG similarly increased, but these high levels were
      maintained after 24 h. These results suggest that gamma-TDMG may be a more
      effective source of gamma-Toc in skin. Thus, the topical application of gamma
      TDMG may be efficacious for the prevention of UV-B-induced skin damage.

PMID- 15745422
TI  - Determination of stereochemistry of bacteriochlorophyll gF and 8(1)-hydroxy
      chlorophyll aF from Heliobacterium modesticaldum.
AB  - The reaction center complex of heliobacteria contains three kinds of chlorophyll
      pigments, bacteriochlorophyll gF (BChl gF), its 13(2)-epimer BChl gF' and 8(1)
      hydroxy-chlorophyll aF (8(1)-OH-Chl aF). Because the full stereochemistry of
      these naturally occurring chlorophyllous pigments has remained unknown, we
      determined the stereochemistry of both BChl gF and 8(1)-OH-Chl aF extracted from
      Heliobacterium modesticaldum. The configurations of the specific functional
      groups at ring-B as well as those at ring-D and -E were investigated by use of
      nuclear Overhauser effect correlations in their 1H-NMR spectra and circular
      dichroism spectra, as well as by modified Mosher's method in their chemical
      modification: (1) E-configuration was confirmed for the 8-ethylidene group at
      ring-B in BChl gF, (2) R-configuration was identified for the 1-hydroxyethyl
      group at ring-B in 8(1)-OH-Chl aF and (3) 13(2)-(R)-, 17-(S)- and 18-(S)
      configurations at ring-D and -E in both BChl gF and 8(1)-OH-Chl aF were
      confirmed. These stereochemistries enabled us to discuss their biosynthesis and
      to propose possible routes for preparation of ethylidene and 1-hydroxyethyl
      groups at the 8-position.

PMID- 15745424
TI  - High UV-B exposures in the continental USA: towards realistic short-term exposure
      regimes for plant-effects research.
AB  - Understanding the biological effects of acute ultraviolet-B (UV-B) exposure
      requires understanding the typical intensity and duration of such exposures. The
      occurrence of high hourly biologically effective UV-B (UV-B(BE)) exposures was
      evaluated using two response functions (1971 and 2003) for the 1997-2002 summer
      growing seasons (May-August) at five locations across the continental United
      States. The frequency of occurrence of the upper 5% of all seasonal UV-B(BE)
      hourly exposures of 1 h to 4 h duration in 1 day and repeating the same exposure
      over consecutive days was evaluated. High hourly UV-B(BE) exposures occurred most
      frequently during June and July. There was a 30% frequency of occurrence of a day
      during the growing season with 2 h of hourly exposure in the upper 5% of UV-B(BE)
      (1971) values across any of the five locations studied. The frequency of
      occurrence of 2 h of UV-B(BE) (2003) exposure in the uppermost 5% of all observed
      hourly values was 14%. An approach and specific experimental square-wave
      enhancement exposure regimes that are consistent with the range of actual
      exposures and total ozone column (TOC) during the May through August period are
      provided. A 2 day high UV-B event with 2 h of high UV-B(BE) occurred at least 10%
      of all days in the growing season, representing a reasonable short-term high
      exposure regime. Different exposure statistics and resulting enhancement regimes
      would likely result if only June and July were included in the analysis.

PMID- 15745425
TI  - Light quality influences indigo precursors production and seed germination in
      Isatis tinctoria L. and Isatis indigotica Fort.
AB  - Isatis tinctoria L. and Isatis indigotica Fort. are biennial herbaceous plants
      belonging to the family of Cruciferae that are used as a source of natural indigo
      and show several morphological and genetic differences. Production of indigo
      (indigotin) precursors, indican (indoxyl beta-D glucoside) and isatan B (indoxyl
      ketogluconate), together with seed germination ability were compared in Isatis
      tinctoria and Isatis indigotica grown under six different light conditions
      (darkness, white, red, far red, blue, yellow light) at 25 degrees C. Light
      quality influenced both germination and production of indigo precursors in the
      two Isatis species. Different responsiveness to far red and blue light was
      observed. Indeed, a detrimental effect on germination by blue and far red light
      was found in I. tinctoria only. Different amounts of isatan B were produced under
      red and far red light in the two Isatis species. In I. tinctoria, the level of
      main indigo precursor isatan B was maximal under red light and minimal under far
      red light. Whereas in I. indigotica far red light promoted a large accumulation
      of isatan B. The photon fluence rate dependency for white and yellow light
      responses showed that the accumulation of indigo precursors was differently
      influenced in the two Isatis species. In particular, both white and yellow light
      enhanced above 40 micromol m(-2) s(-1) the production of isatan B in I.
      indigotica while only white light showed a photon fluence dependency in I.
      tinctoria. These results suggest a different role played by the labile and stable
      phytochrome species (phyA and phyB) in the isatan B production in I. tinctoria
      and I. indigotica. I. indigotica, whose germination percentage was not influenced
      by light quality, demonstrated higher germination capability compared with I.
      tinctoria. In fact, I. tinctoria showed high frequency of germination in darkness
      and under light sources that establish high phytochrome photoequilibrium (red,
      white and yellow light). Germination in I. tinctoria was negatively affected by
      far red and blue light. I. indigotica seeds appear to be indifferent to canopy
      like light (far red). Our results provide further insights on the distinct
      behaviour of I. tinctoria and I. indigotica that belong to two different genetic
      clusters and different original environments.

PMID- 15745423
TI  - Studies on the subcellular localization of the porphycene CPO.
AB  - This study was designed to provide more detailed information on the subcellular
      sites of binding of the porphycene, termed 9-capronyloxytetrakis (methoxyethyl)
      porphycene (CPO), with a fluorescence resonance energy transfer (FRET) technique.
      The proximity of CPO to two fluorescent probes was determined: nonyl acridine
      orange (NAO), a dye with specific affinity for the mitochondrial lipid
      cardiolipin, and dihexa-oxacarbocyanine iodide (DiOC6), an agent that labels the
      endoplasmic reticulum (ER). FRET spectra indicated energy transfer between DiOC6
      and CPO but no significant transfer between NAO and CPO. These results confirm
      data obtained by fluorescence microscopy, suggesting a similar pattern of
      subcellular localization by CPO and DiOC6 but not by CPO and NAO. However, when
      cells containing CPO were irradiated and then loaded with NAO, FRET between the
      two fluorophores was observed. Hence, a relocalization of CPO can occur during
      irradiation. These data provide an explanation for recent studies on CPO
      catalyzed photodamage to both ER and mitochondrial Bcl-2.

PMID- 15745427
TI  - Chloroform infrared multiphoton dissociation in the presence of O2 and NO2.
AB  - The infrared multiphoton dissociation (IRMPD) of CDCl3 in the presence of O2 and
      NO2 as acceptor gases has been studied. We have worked with both pure CDCl3 and
      mixtures with CHCl3. The reaction mechanism following IRMPD of CDCl3 is discussed
      in detail. CCl2O, CCl4 and DCl were found to be the main products. With added O2,
      the observed CDCl3 dissociation was larger than with nonoxygenated acceptor
      gases. The reaction mechanism probably involves a catalytic cycle initiated by
      the oxidation of CCl3. With the aim of discriminating the different CDCl3
      dissociation mechanisms, the IRMPD of CDCl3 in the presence of NO2 was first
      studied. In order to make evident the CDCl3 dissociation produced by the
      catalytic cycle, we then studied the IRMPD of CDCl3 in mixtures with CHCl3 with
      O2 as the acceptor gas. In this case, the dissociation mechanism subsequent to
      IRMPD is evidenced in the competence between the two isotopic species.

PMID- 15745426
TI  - Proteome analysis of UV-B-induced anti-apoptotic regulatory factors.
AB  - Ultraviolet (UV) irradiation is well known to induce apoptosis, a hallmark event
      of which is the occurrence of sunburn cells in the epidermis. Keratinocytes in
      which DNA damaged by UV irradiation is not repaired undergo apoptosis as sunburn
      cells. However, we have previously reported that low-dose UV-B irradiation
      (approximately 0.1 J/cm2) suppressed the apoptosis induced by cell detachment and
      serum depletion. Dysregulation of apoptosis is important in tumor progression and
      malignancy and in promoting resistance to cancer therapy. To develop a better
      understanding of the antiapoptotic effect of UV irradiation, and to design the
      effective induction of apoptosis, we tried the proteome analysis of the molecules
      regulating apoptosis in low-dose UV-B-irradiated NIH3T3 cells, using two
      dimensional difference gel electrophoresis (DIGE). Of a total of 3811 protein
      spots detected, 42 were found to be different between the cells undergoing
      apoptosis and cells after the irradiation. Of the spots selected, 25 were
      identified using MALDI-TOF/TOF-MS, some as structural proteins. Although typical
      apoptosis-related molecules were not detected, possibly because proteins with low
      molecular weights were difficult to identify in the gel conditions used in this
      study, some of the proteins were considered to be involved in apoptosis. The DIGE
      system used in this experiment has advantages (including a high level of
      statistical confidence) for discovering new functional proteins related to the
      regulation of apoptosis.

PMID- 15745428
TI  - Photooxidative treatment of sulfurous water for its potabilization.
AB  - The feasibility of potabilization of sulfurous water was investigated by
      photochemical oxidation processes using a batch photoreactor and a continuous
      flow photoreactor, equipped with UV lamps of 1000 W and 1500 W, respectively.
      Additionally, two advanced processes of oxidation were applied i.e. with a use of
      a UV light/H2O2/air and UV light/H2O2/O3/air. These two processes were compared
      for their efficiency to the direct oxidation process where ozone is used in the
      absence of UV light. Results obtained for both advanced processes showed better
      oxidation than takes place by ozone in the absence of UV light. After the
      photooxidation processes, different processes for the absorption or precipitation
      of sulfates were investigated to comply with the World Health Organization (WHO)
      norm that demands a limit of < or =250 mg L(-1) of SO4(2-) in drinking water.
      Additionally, reverse osmosis was simulated using Osmonics Inc. software to
      predict the feasibility of lowering the salt concentration below WHO limits.

PMID- 15745432
TI  - Hope against the cold: individual differences in trait hope and acute pain
      tolerance on the cold pressor task.
AB  - Hope theory (see Snyder, 1994) is presented as a useful framework for
      understanding reactions to pain. In Study 1, persons scoring higher on the trait
      Hope Scale (Snyder, Harris et al., 1991) kept their hands in the freezing water
      (of a cold pressor task) for significantly longer. In Study 2, the higher-hope
      males, and not females, as measured by both trait and state hope (Snyder, Sympson
      et al., 1996), recognized the onset of the pain threshold significantly later.
      Moreover, in Study 2, results showed that individual differences measures of
      optimism, self-efficacy, depression, and positive and negative affects did not
      relate to the pain onset and tolerance variables. The implications of hope as
      related to the pain process and related research are discussed.

PMID- 15745433
TI  - Dispositional forgiveness of self, others, and situations.
AB  - Six studies regarding forgiveness are presented. The Heartland Forgiveness Scale
      (HFS), a self-report measure of dispositional forgiveness (with subscales to
      assess forgiveness of self, others, and situations) was developed and
      demonstrated good psychometric properties. Forgiveness correlated positively with
      cognitive flexibility, positive affect, and distraction; it correlated negatively
      with rumination, vengeance, and hostility. Forgiveness predicted four components
      of psychological well-being (anger, anxiety, depression, and satisfaction with
      life); forgiveness of situations accounted for unique variance in these
      components of psychological well-being. Forgiveness and hostility demonstrated
      equivalent, inverse associations with relationship duration, and forgiveness
      accounted for unique variance in relationship satisfaction, even when controlling
      for trust. Forgiveness level correlated positively with decreased negativity in
      statements written about transgressions in the present versus the past tense.

PMID- 15745434
TI  - The relative contribution of trait and social influences to the links among
      perceived social support, affect, and self-esteem.
AB  - Although perceived support is influenced by both the personality traits of
      support recipients as well as various social factors, it is unknown to what
      extent these two types of influences account for perceived support's link to
      mental health. We investigated these relations using multivariate
      generalizability analyses. In three samples, both the trait and social influence
      components of perceived support were related to favorable affect and to self
      esteem. The magnitude of the correlations between perceived support and mental
      health was similar for both the trait and social influence components. Similar
      findings were obtained for social conflict, although the links between conflict
      and mental health varied somewhat depending upon the level of analysis. These
      findings suggest that social support theories and interventions should include
      both trait and social mechanisms to explain and modify perceived support and
      mental health.

PMID- 15745429
TI  - Anthocyanins protect against A2E photooxidation and membrane permeabilization in
      retinal pigment epithelial cells.
AB  - The pyridinium bisretinoid A2E, an autofluorescent pigment that accumulates in
      retinal pigment epithelial cells with age and in some retinal disorders, can
      mediate a detergent-like perturbation of cell membranes and light-induced damage
      to the cell. The photodynamic events initiated by the sensitization of A2E
      include the generation of singlet oxygen and the oxidation of A2E at carbon
      carbon double bonds. To assess the ability of plant-derived anthocyanins to
      modulate adverse effects of A2E accumulation on retinal pigment epithelium (RPE)
      cells, these flavylium salts were isolated from extracts of bilberry. Nine
      anthocyanin fractions reflecting monoglycosides of delphinidin, cyanidin,
      petunidin and malvidin were obtained and all were shown to suppress the
      photooxidation of A2E at least in part by quenching singlet oxygen. The
      anthocyanins tested exhibited antioxidant activity of variable efficiency. The
      structural characteristics relevant to this variability likely included the
      ability to form a stable quinonoidal anhydro base at neutral pH, a conjugated
      diene structure in the C (pyrane) ring, the presence of hydroxyl groups on the B
      (benzene) ring and the relative hydrophobicity conferred by the arrangement of
      substituents on the B ring. Cells that had taken up anthocyanins also exhibited a
      resistance to the membrane permeabilization that occurs as a result of the
      detergent-like action of A2E.

PMID- 15745435
TI  - A chimpanzee (Pan troglodytes) analogue of cross-national generalization of
      personality structure: zoological parks and an African sanctuary.
AB  - Six personality factors, including five resembling the human Big Five, had
      previously been identified in a separate group of zoo-housed chimpanzees.
      Comparability of chimpanzee personality factor structure was examined in two
      highly contrasting habitats: zoos and a large African sanctuary. Questionnaires
      for the zoo chimpanzees were in English, while most for the chimpanzees in the
      sanctuary were in French. Differences between the two settings were sufficiently
      extensive to make them analogous to cross-national human personality studies.
      Internal consistencies for five of the six factors did not differ between the two
      samples. The patterns of correlations between the unit-weighted factors were also
      similar for the two samples. Data from these two samples were pooled and factor
      analyzed. The resulting factor structure was then rotated to the factor structure
      described in the original study of chimpanzee personality. Dominance,
      Extraversion, Dependability, and Agreeableness had high congruences. Emotionality
      and Openness did not, but the items that had the highest loadings were consistent
      with the factors' definitions. Finally, sex and age effects for all factors
      generalized across habitats.

PMID- 15745436
TI  - Costs of self-handicapping.
AB  - Four studies examined the relation of trait self-handicapping with health-related
      measures. Study 1 showed that, over time, self-handicapping and maladjustment
      reinforce each other. Study 2 showed that self-handicappers reported a loss in
      competence satisfaction which, in turn, mediated the relation of self
      handicapping with negative mood. Study 3 found that, over time, self-handicappers
      report an increase in substance use. Study 4 showed that self-handicappers
      reported a loss in intrinsic motivation for their jobs. It was suggested that
      people with unstable (or contingent) self-esteem use self-handicapping to bolster
      a fragile self-concept.

PMID- 15745437
TI  - How to resist temptation: the effects of external control versus autonomy support
      on self-regulatory dynamics.
AB  - The purpose of the present study (N=80 undergraduate students) was to examine two
      issues: first, does external control lead to an increase in resistance to
      temptation more than the use of autonomy support? Second, what are the long-term
      effects of these types of educational style? Based on the Personality Systems
      Interaction (PSI) theory, external control was expected to increase resistance to
      temptation for those participants who lack initiative and self-motivation (i.e.,
      state-oriented participants). Consistent with expectations, resistance to
      temptation was greater for state-oriented participants with externally controlled
      instructions than for individuals who received autonomy-supportive instructions.
      This was reflected by their performance on a visual discrimination task during
      distracter, compared to baseline, episodes. However, external control had
      negative long-term effects on state-oriented participants as indexed by
      alienation from their own preferences in free-choice behavior. Action-oriented
      participants were less influenced by experimental conditions.

PMID- 15745438
TI  - Genetic and environmental influences on religiousness: findings for retrospective
      and current religiousness ratings.
AB  - Estimates of the degree of genetic and environmental influences on religiousness
      have varied widely. This variation may, in part, be due to age differences in the
      samples under study. To investigate the heritability of religiousness and
      possible age changes in this estimate, both current and retrospective
      religiousness were assessed by self-report in a sample of adult male twins (169
      MZ pairs and 104 DZ pairs, mean age of 33 years). Retrospective reports of
      religiousness showed little correlation difference between MZ (r=.69) and DZ
      (r=.59) twins. Reports of current religiousness, however, did show larger MZ
      (r=.62) than DZ (r=.42) similarity. Biometric analysis of the two religiousness
      ratings revealed that genetic factors were significantly weaker (12% vs. 44%) and
      shared environmental factors were significantly stronger (56% vs. 18%) in
      adolescence compared to adulthood. Analysis of internal and external
      religiousness subscales of the total score revealed similar results. These
      findings support the hypothesis that the heritability of religiousness increases
      from adolescence to adulthood.

PMID- 15745439
TI  - Do people know how their personality has changed? Correlates of perceived and
      actual personality change in young adulthood.
AB  - How much do we think our personality changes over time? How well do our
      perceptions of change correspond with actual personality change? Two hundred and
      ninety students completed measures of the Big Five personality traits when they
      first entered college. Four years later, they completed the same measures and
      rated the degree to which they believed they had changed on each dimension.
      Participants tended to view themselves as having changed substantially, and
      perceptions of change showed some correspondence with actual personality change.
      Perceived and actual change showed theoretically meaningful correlations with a
      host of variables related to different aspects of college achievement and
      adjustment.

PMID- 15745440
TI  - Personality stability in late adulthood: a behavioral genetic analysis.
AB  - A sample of 833 twins from the Minnesota Twin Study of Adult Development and
      Aging completed the Multidimensional Personality Questionnaire (MPQ; Tellegen,
      1982) twice, averaging 59.4 (sd=9.7) years of age at first and 64.4 (sd=10.2)
      years of age at second testing (average retest interval 5.0 years, sd=2.36, range
      1.0-10.4 years). Both means and standard deviations of scale scores were
      extremely stable from first to second testing. In addition, sample participants
      tended to retain their rank order on the scales (average r=.76 across scales).
      Bivariate biometric analyses showed that the genetic influences on most of the
      scale scores were almost perfectly correlated across the two waves (range .95 to
      1.00). The nonshared environmental influences were also highly correlated across
      the two waves (range .53 to .73). Models specifying identical variance components
      at the two time points and fixing the genetic correlation to 1.00 provided
      improved fit. The results suggest that the high stability of personality in later
      adulthood has a strong genetic foundation, supplemented by stability of
      environmental effects.

PMID- 15745442
TI  - Influence of antioxidant (L- ascorbic acid) on tolbutamide induced
      hypoglycaemia/antihyperglycaemia in normal and diabetic rats.
AB  - BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by
      hyperglycaemia. Increased oxidative stress and decreased antioxidant levels are
      the leading cause of diabetes and diabetic complications. So it is felt that
      supplementation of antioxidants may be useful in controlling the glucose levels
      and to postpone the occurrence of diabetic complications. The objective of our
      study is to find the influence of antioxidant supplementation (L-ascorbic acid)
      on tolbutamide activity in normal and diabetic rats. METHODS: L- ascorbic
      acid/tolbutamide/L-ascorbic acid + tolbutamide were administered orally to 3
      different groups of albino rats of either sex in normal and diabetic condition.
      Blood samples were collected from retro-orbital puncture at different time
      intervals and were analyzed for blood glucose by GOD-POD method. Diabetes was
      induced by alloxan 100 mg/kg body weight administered by I.P route. RESULTS: L
      ascorbic acid/ tolbutamide produced hypoglycaemic activity in a dose dependant
      manner in normal and diabetic condition. In the presence of L-ascorbic acid,
      tolbuatmide produced early onset of action and maintained for longer period
      compared to tolbutamide matching control. CONCLUSION: Supplementation of
      antioxidants like L-ascorbic acid was found to improve tolbutamide response in
      normal and diabetic rats.

PMID- 15745441
TI  - Use of biological based therapy in patients with cardiovascular diseases in a
      university-hospital in New York City.
AB  - BACKGROUND: The use of complementary and alternative products including
      Biological Based Therapy (BBT) has increased among patients with various medical
      illnesses and conditions. The studies assessing the prevalence of BBT use among
      patients with cardiovascular diseases are limited. Therefore, an evaluation of
      BBT in this patient population would be beneficial. This was a survey designed to
      determine the effects of demographics on the use of Biological Based Therapy
      (BBT) in patients with cardiovascular diseases. The objective of this study was
      to determine the effect of the education level on the use of BBT in
      cardiovascular patients. This survey also assessed the perceptions of users
      regarding the safety/efficacy of BBT, types of BBT used and potential BBT-drug
      interactions. METHOD: The survey instrument was designed to assess the findings.
      Patients were interviewed from February 2001 to December 2002. 198 inpatients
      with cardiovascular diseases (94 BBT users and 104 non-users) in a university
      hospital were included in the study. RESULTS: Users had a significantly higher
      level of education than non-users (college graduate: 28 [30%] versus 12 [12%], p
      = 0.003). Top 10 BBT products used were vitamin E [41(43.6%)], vitamin C
      [30(31.9%)], multivitamins [24(25.5%)], calcium [19(20.2%)], vitamin B complex
      [17(18.1%)], fish oil [12(12.8%)], coenzyme Q10 [11(11.7%)], glucosamine
      [10(10.6%)], magnesium [8(8.5%)] and vitamin D [6(6.4%)]. Sixty percent of users'
      physicians knew of the BBT use. Compared to non-users, users believed BBT to be
      safer (p < 0.001) and more effective (p < 0.001) than prescription drugs. Forty
      two potential drug-BBT interactions were identified. CONCLUSION: Incidence of use
      of BBT in cardiovascular patients is high (47.5%), as is the risk of potential
      drug interaction. Health care providers need to monitor BBT use in patients with
      cardiovascular diseases.

PMID- 15745443
TI  - Socioeconomic factors and low birth weight in Mexico.
AB  - BACKGROUND: Low birth weight (LBW) is a public health problem linked to lack of
      equity in populations. Despite efforts to decrease the proportion of newborns
      with LBW, success has been quite limited. In recent years, studies focused on
      explaining how social factors influence this problem have shown that populations
      with greater inequities have a greater proportion of newborns with LBW. METHODS:
      The objective was to describe socioeconomic factors related to LBW adjusted by
      demographic, reproductive and health services variables in Mexico City. A case
      control study was carried out in three hospitals with gynaecological and
      obstetrics services in Mexico City during the first half of 1996. During the
      recruiting period all children with LBW (cases), defined as newborns weighing
      <2500 grams, were matched with children born on the same day to control for time
      of birth. Upon arrival at the hospital for delivery, women were interviewed to
      determine if they met our inclusion criteria. Women with a history of chronic
      conditions and those with twin or multiple pregnancies were excluded. Variables
      with clinical and statistical significance were included in a multivariate model
      (logistic regression). RESULTS: We found that low socioeconomic level was the
      most important risk factor for LBW and was independent of other factors,
      including those related to reproduction and nutrition, smoking, morbidity during
      pregnancy, accessibility to health services and prenatal care (OR 2.68; 95% CI
      1.19, 6.03). CONCLUSION: We found that socioeconomic factors are relevant to LBW.
      However further research should be done in different population groups as well as
      developing precise ways of measuring socioeconomic factors and their role in
      reproductive health.

PMID- 15745445
TI  - The role of mast cells in the pathogenesis of pain in chronic pancreatitis.
AB  - BACKGROUND: The biological basis of pain in chronic pancreatitis is poorly
      understood. Mast cells have been implicated in the pathogenesis of pain in other
      conditions. We hypothesized that mast cells play a role in the pain of chronic
      pancreatitis. We examined the association of pain with mast cells in autopsy
      specimens of patients with painful chronic pancreatitis. We explored our
      hypothesis further using an experimental model of trinitrobenzene sulfonic acid
      (TNBS) -induced chronic pancreatitis in both wild type (WT) and mast cell
      deficient mice (MCDM). METHODS: Archival tissues with histological diagnoses of
      chronic pancreatitis were identified and clinical records reviewed for presence
      or absence of reported pain in humans. Mast cells were counted. The presence of
      pain was assessed using von Frey Filaments (VFF) to measure abdominal withdrawal
      responses in both WT and MCDM mice with and without chronic pancreatitis.
      RESULTS: Humans with painful chronic pancreatitis demonstrated a 3.5-fold
      increase in pancreatic mast cells as compared with those with painless chronic
      pancreatitis.WT mice with chronic pancreatitis were significantly more sensitive
      as assessed by VFF pain testing of the abdomen when compared with MCDM.
      CONCLUSION: Humans with painful chronic pancreatitis have an increased number of
      pancreatic mast cells as compared with those with painless chronic pancreatitis.
      MCDM are less sensitive to mechanical stimulation of the abdomen after induction
      of chronic pancreatitis as compared with WT. Mast cells may play an important
      role in the pathogenesis of pain in chronic pancreatitis.

PMID- 15745444
TI  - Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced
      liver cirrhosis.
AB  - BACKGROUND: The exogenous administration of Insulin-like Growth Factor-I (IGF-I)
      induces hepatoprotective and antifibrogenic actions in experimental liver
      cirrhosis. To better understand the possible pathways behind the beneficial
      effect of IGF-I, the aim of this work was to investigate severe parameters
      involved in oxidative damage in hepatic tissue from cirrhotic animals treated
      with IGF-I (2 microg x 100 g(-1) x day(-1)). Iron and copper play an important
      role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH)
      that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric
      oxide (NO) are known sources of free radicals and induce reduction of ferritin
      Fe3+ into free Fe2+, contributing to oxidative damage. METHODS: Liver cirrhosis
      was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls
      were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption
      spectrometry and iron content was also evaluated by Perls' staining. MPO was
      measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS
      expression was studied by immuno-histochemistry. RESULTS: Liver cirrhosis was
      histologically proven and ascites was observed in all cirrhotic rats. Compared to
      controls untreated cirrhotic rats showed increased hepatic levels of iron,
      ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01).
      However, IGF-treatment induced a significant reduction of all these parameters (p
      < 0.05). CONCLUSION: the hepatoprotective and antifibrogenic effects of IGF-I in
      cirrhosis are associated with a diminution of the hepatic contents of several
      factors all of them involved in oxidative damage.

PMID- 15745446
TI  - Clinical outcome of endonasal KTP laser assisted dacryocystorhinostomy.
AB  - BACKGROUND: To evaluate the clinical outcome of primary endonasal laser assisted
      dacryocystorhinostomy (ENL-DCR) using the potassium-titanyl-phosphate laser.
      METHODS: We retrospectively reviewed all primary ENL-DCRs performed within a
      period of twelve months by the same combined Ophthalmology and
      Otorhinolaringology team in Freeman Hospital, Newcastle upon Tyne, UK. The main
      outcome measure for success was resolution or significant improvement of
      epiphora. Details of surgery, intraoperative and postoperative complications, as
      well as pathology associated with failure were also studied. Patients were
      followed up for at least 12 months. RESULTS: A total of 41 consecutive ENL-DCRs
      on 29 patients (22 females, 7 males, mean age 75 years) were analysed. All
      patients had bicanalicular silicone intubation for at least 4 months. The success
      rate at 12 months postoperatively was 78.1%. Pathology associated with failure
      included: intranasal pathology (12.2%), mucocele (7.3%), and systemic sarcoidosis
      (2.4%). No significant intra-operative complications were recorded. CONCLUSION:
      The ENL-DCR with potassium-titanyl-phosphate laser can be considered as a safe
      and efficient primary procedure for the treatment of nasolacrimal duct
      obstruction.

PMID- 15745447
TI  - Distributional interaction: Interpretational problems when using incidence odds
      ratios to assess interaction.
AB  - It is well known that the incidence odds ratio approximates the risk ratio when
      the disease of interest is rare, but increasingly overestimates the risk ratio as
      the disease becomes more common. However when assessing interaction, incidence
      odds ratios may not approximate risk ratios even when the disease is rare. We use
      the term "distributional interaction" to refer to interaction that appears when
      using incidence odds ratios that does not appear, or appears to a lesser degree,
      when using risk ratios. The interpretational problems that arise from this
      discrepancy can have important implications in epidemiologic research. Therefore,
      quantification of the relationship between the interaction odds ratio and the
      interaction risk ratio is warranted. In this paper, we provide a formula to
      quantify the differences between incidence odds ratios and risk ratios when they
      are used to estimate effect modification on a multiplicative scale. Using this
      formula, we examine the conditions under which these two estimates diverge.
      Furthermore, we expand this discussion to the implications of using incidence
      odds ratios to assess effect modification on an additive scale. Finally, we
      illustrate how distributional interaction arises and the problems that it causes
      using an example from the literature. Whenever the risk of the outcome variable
      is non-negligible, distributional interaction is possible. This is true even when
      the disease is rare (e.g., disease risk is less than 5%). Therefore, when
      assessing interaction on either an additive or multiplicative scale, caution
      should be taken in interpreting interaction estimates based on incidence odds
      ratios.

PMID- 15745448
TI  - The efficacy of playing a virtual reality game in modulating pain for children
      with acute burn injuries: a randomized controlled trial [ISRCTN87413556].
AB  - BACKGROUND: The management of burn injuries is reported as painful, distressing
      and a cause of anxiety in children and their parents. Child's and parents' pain
      and anxiety, often contributes to extended time required for burns management
      procedures, in particular the process of changing dressings. The traditional
      method of pharmacologic analgesia is often insufficient to cover the burnt
      child's pain, and it can have deleterious side effects 12. Intervention with
      Virtual Reality (VR) games is based on distraction or interruption in the way
      current thoughts, including pain, are processed by the brain. Research on adults
      supports the hypothesis that virtual reality has a positive influence on burns
      pain modulation. METHODS: This study investigates whether playing a virtual
      reality game, decreases procedural pain in children aged 5-18 years with acute
      burn injuries. The paper reports on the findings of a pilot study, a randomised
      trial, in which seven children acted as their own controls though a series of 11
      trials. Outcomes were pain measured using the self-report Faces Scale and
      findings of interviews with parent/carer and nurses. RESULTS: The average pain
      scores (from the Faces Scale) for pharmacological analgesia only was, 4.1 (SD
      2.9), while VR coupled with pharmacological analgesia, the average pain score was
      1.3 (SD 1.8) CONCLUSION: The study provides strong evidence supporting VR based
      games in providing analgesia with minimal side effects and little impact on the
      physical hospital environment, as well as its reusability and versatility,
      suggesting another option in the management of children's acute pain.

PMID- 15745449
TI  - Assessment of obesity management in medical examination.
AB  - Obesity is a growing international health problem that has already reached
      epidemic proportions, particularly within the United States where a majority of
      the population is overweight or obese. Effective methods of treatment are needed,
      and should be taught to physicians by efficient means. There exists a disconnect
      between the rising obesity prevalence with its high toll on medical resources,
      and the lack of obesity education provided to practitioners in the course of
      their training. One particular shortfall is the lack of representation of obesity
      on standardized medical examinations. Physician attitudes toward obesity are
      influenced by their lack of familiarity with the management of the disease. This
      may include dietary restriction, increasing physical activity, behavior
      modification, pharmacotherapy, and surgical interventions. Thus, curricular
      changes in the medical education of obesity could help reduce morbidity and
      mortality associated with this disease.

PMID- 15745452
TI  - Preprandial ghrelin is not affected by macronutrient intake, energy intake or
      energy expenditure.
AB  - BACKGROUND: Ghrelin, a peptide secreted by endocrine cells in the
      gastrointestinal tract, is a hormone purported to have a significant effect on
      food intake and energy balance in humans. The influence of factors related to
      energy balance on ghrelin, such as daily energy expenditure, energy intake, and
      macronutrient intake, have not been reported. Secondly, the effect of ghrelin on
      food intake has not been quantified under free-living conditions over a prolonged
      period of time. To investigate these effects, 12 men were provided with an ad
      libitum cafeteria-style diet for 16 weeks. The macronutrient composition of the
      diets were covertly modified with drinks containing 2.1 MJ of predominantly
      carbohydrate (Hi-CHO), protein (Hi-PRO), or fat (Hi-FAT). Total energy
      expenditure was measured for seven days on two separate occasions (doubly labeled
      water and physical activity logs). RESULTS: Preprandial ghrelin concentrations
      were not affected by macronutrient intake, energy expenditure or energy intake
      (all P > 0.05). In turn, daily energy intake was significantly influenced by
      energy expenditure, but not ghrelin. CONCLUSION: Preprandial ghrelin does not
      appear to be influenced by macronutrient composition, energy intake, or energy
      expenditure. Similarly, ghrelin does not appear to affect acute or chronic energy
      intake under free-living conditions.

PMID- 15745454
TI  - A case of invasive aspergillosis in CGD patient successfully treated with
      Amphotericin B and INF-gamma.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is a rare disorder of phagocytes
      in which absence of superoxide and hydrogen peroxide production in phagocytes
      predisposes patients to bacterial and fungal infections. The most common fungal
      infections in these patients are caused by Aspergillus species. CASE
      PRESENTATION: Here, we describe Aspergillus osteomyelitis of the ribs and hepatic
      abscess in a 5-year-old boy. The patient was successfully treated with
      Amphotericin B and INF-gamma. CONCLUSION: With respect to the high frequency of
      aspergillosis in the CGD patient, immune deficiency should be investigated in
      patients with invasive aspergillosis. Moreover, using antifungal drugs as
      prophylaxis can improve the quality of life in these patients.

PMID- 15745453
TI  - Bacillus subtilis actin-like protein MreB influences the positioning of the
      replication machinery and requires membrane proteins MreC/D and other actin-like
      proteins for proper localization.
AB  - BACKGROUND: Bacterial actin-like proteins have been shown to perform essential
      functions in several aspects of cellular physiology. They affect cell growth,
      cell shape, chromosome segregation and polar localization of proteins, and
      localize as helical filaments underneath the cell membrane. Bacillus subtilis
      MreB and Mbl have been shown to perform dynamic motor like movements within
      cells, extending along helical tracks in a time scale of few seconds. RESULTS: In
      this work, we show that Bacillus subtilis MreB has a dual role, both in the
      formation of rod cell shape, and in chromosome segregation, however, its function
      in cell shape is distinct from that of MreC. Additionally, MreB is important for
      the localization of the replication machinery to the cell centre, which becomes
      aberrant soon after depletion of MreB. 3D image reconstructions suggest that
      frequently, MreB filaments consist of several discontinuous helical filaments
      with varying length. The localization of MreB was abnormal in cells with
      decondensed chromosomes, as well as during depletion of Mbl, MreBH and of the
      MreC/MreD proteins, which we show localize to the cell membrane. Thus, proper
      positioning of MreB filaments depends on and is affected by a variety of factors
      in the cell. CONCLUSION: Our data provide genetic and cytological links between
      MreB and the membrane, as well as with other actin like proteins, and further
      supports the connection of MreB with the chromosome. The functional dependence on
      MreB of the localization of the replication machinery suggests that the replisome
      is not anchored at the cell centre, but is positioned in a dynamic manner.

PMID- 15745455
TI  - Increased daily physical activity and fatigue symptoms in chronic fatigue
      syndrome.
AB  - Individuals with chronic fatigue syndrome (CFS) have been shown to have reduced
      activity levels associated with heightened feelings of fatigue. Previous research
      has demonstrated that exercise training has beneficial effects on fatigue-related
      symptoms in individuals with CFS. PURPOSE: The aim of this study was to sustain
      an increase in daily physical activity in CFS patients for 4 weeks and assess the
      effects on fatigue, muscle pain and overall mood. METHODS: Six CFS and seven
      sedentary controls were studied. Daily activity was assessed by a CSA
      accelerometer. Following a two week baseline period, CFS subjects were asked to
      increase their daily physical activity by 30% over baseline by walking a
      prescribed amount each day for a period of four weeks. Fatigue, muscle pain and
      overall mood were reported daily using a 0 to 100 visual analog scale and weekly
      using the Profile of Mood States (Bipolar) questionnaire. RESULTS: CFS patients
      had significantly lower daily activity counts than controls (162.5 +/- 51.7 x 103
      counts/day vs. 267.2 +/- 79.5 x 103 counts/day) during a 2-week baseline period.
      At baseline, the CFS patients reported significantly (P < 0.01) higher fatigue
      and muscle pain intensity compared to controls but the groups did not differ in
      overall mood. CFS subjects increased their daily activity by 28 +/- 19.7% over a
      4 week period. Overall mood and muscle pain worsened in the CFS patients with
      increased activity. CONCLUSION: CFS patients were able to increase their daily
      physical activity for a period of four weeks. In contrast to previous studies
      fatigue, muscle pain, and overall mood did not improve with increased activity.
      Increased activity was not presented as a treatment which may account for the
      differential findings between this and previous studies. The results suggest that
      a daily "activity limit" may exist in this population. Future studies on the
      impact of physical activity on the symptoms of CFS patients are needed.

PMID- 15745456
TI  - A murine model of ulcerative colitis: induced with sinusitis-derived superantigen
      and food allergen.
AB  - BACKGROUND: The etiology of ulcerative colitis (UC) is to be understood. The
      basic pathological feature of UC is intestinal chronic inflammation.
      Superantigen, such as Staphylococcus enterotoxin B (SEB), is reported to
      compromise intestinal barrier function by increasing epithelial permeability and
      initiate inflammation in the intestinal mucosa. Inasmuch as anatomic position of
      the sinus, chronic sinusitis-derived SEB may follow the secretion and to be
      swallowed down to the gastrointestinal tract and induce lesions to the intestinal
      mucosa. METHODS: Sinus wash fluid (SWF, containing SEB) was collected from a
      group of patients with both chronic sinusitis (CS) and UC. A group of mice were
      sensitized to ovalbumin (OVA) in the presence of SWF. The sensitized mice were
      challenged with the specific antigen OVA. The inflammatory status of the colonic
      tissue was determined with histology, serology and electron microscopy. Using
      horseradish peroxidase (HRP) as a tracer, another group of mice was stimulated
      with SWF for 2 hours. The HRP activity was detected in the colonic tissue with
      enzymatic approaches and electron microscopy. RESULTS: Epithelial
      hyperpermeability in colonic epithelium was induced by stimulating with SWF. The
      HRP activity in the colonic mucosa was almost 11 times more in the SWF treated
      group (3.2 +/- 0.6 microg/g tissue) than the control group (0.3 +/- 0.1 microg/g
      tissue). Mice were sensitized using a mixture of SWF and OVA (serum OVA-specific
      IgE was detected with a highest titer as 1:64). Challenge with OVA induced
      extensive inflammation in the colonic mucosa by showing (1) marked degranulation
      in mast cells (MC, 46.3 +/- 4.5%) and eosinophils (Eo, 55.7 +/- 4.2%); (2)
      inflammatory cell infiltration (MC = 145.2 +/- 11.4; Eo = 215.8 +/- 12.5;
      mononuclear cell = 258.4 +/- 15.3/mm2 tissue); (3) increased MPO activity (12.9
      +/- 3.2 U/g tissue) and inflammatory scores (1.8 +/- 0.3); (4) mucosal surface
      ulcers; (5) edema in the lamina propria; (6) bacterial translocation and abscess
      formation in the subepithelial region. CONCLUSION: Introducing Sinusitis-derived
      SEB-containing SWF to the gastrointestinal tract compromised colonic mucosal
      barrier function increasing epithelial permeability to luminal macromolecular
      protein in mice. The SWF facilitated colonic mucosal sensitization to luminal
      antigen. Multiple challenging the sensitized colonic mucosa with specific antigen
      OVA induced inflammation, induced a condition similar to human ulcerative
      colitis.

PMID- 15745458
TI  - Computational model of blood flow in the aorto-coronary bypass graft.
AB  - BACKGROUND: Coronary artery bypass grafting surgery is an effective treatment
      modality for patients with severe coronary artery disease. The conduits used
      during the surgery include both the arterial and venous conduits. Long- term
      graft patency rate for the internal mammary arterial graft is superior, but the
      same is not true for the saphenous vein grafts. At 10 years, more than 50% of the
      vein grafts would have occluded and many of them are diseased. Why do the
      saphenous vein grafts fail the test of time? Many causes have been proposed for
      saphenous graft failure. Some are non-modifiable and the rest are modifiable. Non
      modifiable causes include different histological structure of the vein compared
      to artery, size disparity between coronary artery and saphenous vein. However,
      researches are more interested in the modifiable causes, such as graft flow
      dynamics and wall shear stress distribution at the anastomotic sites. Formation
      of intimal hyperplasia at the anastomotic junction has been implicated as the
      root cause of long- term graft failure. Many researchers have analyzed the
      complex flow patterns in the distal sapheno-coronary anastomotic region, using
      various simulated model in an attempt to explain the site of preferential intimal
      hyperplasia based on the flow disturbances and differential wall stress
      distribution. In this paper, the geometrical bypass models (aorto-left coronary
      bypass graft model and aorto-right coronary bypass graft model) are based on real
      life situations. In our models, the dimensions of the aorta, saphenous vein and
      the coronary artery simulate the actual dimensions at surgery. Both the proximal
      and distal anastomoses are considered at the same time, and we also take into the
      consideration the cross-sectional shape change of the venous conduit from
      circular to elliptical. Contrary to previous works, we have carried out
      computational fluid dynamics (CFD) study in the entire aorta-graft-perfused
      artery domain. The results reported here focus on (i) the complex flow patterns
      both at the proximal and distal anastomotic sites, and (ii) the wall shear stress
      distribution, which is an important factor that contributes to graft patency.
      METHODS: The three-dimensional coronary bypass models of the aorto-right coronary
      bypass and the aorto-left coronary bypass systems are constructed using
      computational fluid-dynamics software (Fluent 6.0.1). To have a better
      understanding of the flow dynamics at specific time instants of the cardiac
      cycle, quasi-steady flow simulations are performed, using a finite-volume
      approach. The data input to the models are the physiological measurements of flow
      rates at (i) the aortic entrance, (ii) the ascending aorta, (iii) the left
      coronary artery, and (iv) the right coronary artery. RESULTS: The flow field and
      the wall shear stress are calculated throughout the cycle, but reported in this
      paper at two different instants of the cardiac cycle, one at the onset of
      ejection and the other during mid-diastole for both the right and left aorto
      coronary bypass graft models. Plots of velocity-vector and the wall shear stress
      distributions are displayed in the aorto-graft-coronary arterial flow-field
      domain. We have shown (i) how the blocked coronary artery is being perfused in
      systole and diastole, (ii) the flow patterns at the two anastomotic junctions,
      proximal and distal anastomotic sites, and (iii) the shear stress distributions
      and their associations with arterial disease. CONCLUSION: The computed results
      have revealed that (i) maximum perfusion of the occluded artery occurs during mid
      diastole, and (ii) the maximum wall shear-stress variation is observed around the
      distal anastomotic region. These results can enable the clinicians to have a
      better understanding of vein graft disease, and hopefully we can offer a solution
      to alleviate or delay the occurrence of vein graft disease.

PMID- 15745460
TI  - Surgical management of ureteropelvic junction obstruction in adults.
AB  - Ureteropelvic junction (UPJ) obstruction is a well-recognized entity that may
      present at any time - in fetal life, infancy, childhood, or early or late
      adulthood. As the most common site of obstruction in the upper urinary tract, the
      UPJ is an area with which urologists should be well familiar. There has been an
      improved understanding of the pathophysiology of primary congenital UPJ
      obstruction that has been reflected in the evolution of surgical options, from
      open surgical repair to minimally invasive surgery. Although the primary scope of
      this review is the surgical management of this condition, we will briefly review
      the pathogenesis, clinical presentation, and diagnosis of UPJ obstruction.

PMID- 15745457
TI  - Human macrophages limit oxidation products in low density lipoprotein.
AB  - This study tested the hypothesis that human macrophages have the ability to
      modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular
      antioxidant defence system. While many studies have focused on macrophage LDL
      oxidation in atherosclerosis development, less attention has been given to the
      cellular antioxidant capacity of these cells. Compared to cell-free controls (6.2
      +/- 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 +/- 0.4 nmol/mg LDL after
      24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were
      3.69 +/- 0.5 nmol/mg LDL in cell-free media, and 2.48 +/- 0.9 nmol/mg LDL in the
      presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7
      +/- 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to
      cell-free incubation (105.0 +/- 14.1 nmol/mg LDL) (P = 0.005). The levels of
      lipid peroxides in oxLDL were 137.9 +/- 59.9 nmol/mg LDL and in cell-free media
      242 +/- 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen
      peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL
      by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a
      high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016).
      The increased levels of glutathione in oxLDL-treated macrophages were accompanied
      by enhanced catalase and glutathione peroxidase activities. Our results suggest
      that macrophages respond to oxidative stress by endogenous antioxidant activity,
      which is sufficient to decrease reactive oxygen species both in LDL and oxLDL.
      This may suggest that the antioxidant activity is insufficient during
      atherosclerosis development. Thus, macrophages may play a dual role in
      atherogenesis, i.e. both by promoting and limiting LDL-oxidation.

PMID- 15745461
TI  - Hand-assisted laparoscopic nephrectomy in living donor.
AB  - OBJECTIVE: Report the authors' initial experience with hand-assisted laparoscopic
      nephrectomy technique in renal donors for transplantation. MATERIALS AND METHODS:
      Twenty-seven donors submitted to hand-assisted laparoscopic nephrectomy were
      retrospectively analyzed from February 2001 to June 2002. Technical aspects of
      the donor surgery, results, and complications, are discussed, as well as
      recipient's complications and outcomes. RESULTS: Among 27 hand-assisted
      laparoscopic nephrectomies, left kidney was withdrew in 18 donors (66.6%), and
      right kidney in 9 (33.3%). The operative time ranged from 55 to 210 minutes (mean
      132.7 + 37.6 min), and the time of hot ischemia ranged from 2 to 11 minutes (mean
      4.7 + 2.5 min), with an estimated mean blood loss during the intraoperative
      period of 133.3 mL. Conversion to open surgery was necessary for 1 (3.7%) patient
      due to vascular lesion. In graft evaluation, immediate diuresis was observed in
      26 (96.3%) cases, and mean serum creatinine in PO day 7 was 1.5 + 1.1 mg/dL.
      Renal vein thrombosis occurred in 1 (3.7%) patient requiring graft removal.
      Lymphocele was observed in 3 recipients (11.1%), and urinary leakage due to
      ureteral necrosis in 1 case (3.7%). CONCLUSION: Hand-assisted laparoscopic
      nephrectomy in living donors is a safe procedure and an effective alternative to
      open nephrectomy. In this series, the procedure presented low morbidity after
      surgery providing to the recipient a good morphological and functional quality of
      the graft.

PMID- 15745462
TI  - Ureteral avulsion as a complication of ureteroscopy.
AB  - PURPOSE: Report and review the literature on ureteral avulsion as a rare
      complication of ureteroscopy. MATERIALS AND METHODS: We analyzed 3 cases of
      ureteral avulsion in a series of 4,645 ureteroscopic procedures performed from
      January 1990 to December 2001. We especially report the different managements for
      this complication. RESULTS: Due to the different extent of the injury, each
      patient was treated in a particular way, including a patient managed by means of
      an endourological approach. CONCLUSIONS: When performing ureteroscopy or using
      Dormia baskets, one should always bear in mind the possibility of serious
      complications, including ureteral avulsion or perforation. The use of an
      extremely careful technique of ureteral insertion, the mandatory placement of a
      safety guidewire, and a working guidewire, all minimize the risk of untoward
      events.

PMID- 15745463
TI  - Efficiency of 6- and 12-punctures biopsies to detect prostate cancer in patients
      with PSA </= 10 ng/mL and normal digital rectal examination.
AB  - OBJECTIVE: Establish the efficiency of 6- and 12-punctures transrectal ultrasound
      guided needle biopsies in low risk patients for prostate cancer. Six-punctures
      (sextant) biopsies were compared to 12-punctures biopsies, assessing which is the
      best strategy to detect this neoplasm. MATERIALS AND METHODS: Among 240 patients
      submitted to prostate biopsy, 54 with suspected small and organ-localized tumors
      (prostatic specific antigen </= 10 ng/mL and digital exam of the prostate not
      suggesting cancer) in glands < 50 cm3 were selected, constituting a homogenous
      sample. These patients were submitted to standard 3-punctures (basal, mid, and
      apical) sextant biopsy in parasagittal midline of each prostatic lobe, with 3
      additional lateral punctures, bilaterally. Each specimen was separately submitted
      to histological study. RESULTS: Twenty-two (40.7%) patients had prostatic cancer,
      and 28 presented prostatic hyperplasia, associated or not to inflammatory
      conditions. High-grade prostatic intraepithelial neoplasia (PIN) was detected in
      4 patients. From 22 tumors detected by 12-punctures biopsies, 6-punctures
      biopsies in the parasagittal midline (sextant) diagnosed 50%of the cases, while
      isolated lateral punctures diagnosed 90.9% of the malignant neoplasms. Basal
      lateral punctures responded for 72.7% of the cancer diagnosis, while basal
      sextant punctures responded only for 9.1% of the cases. CONCLUSION: For low risk
      prostate cancer, patients' 12-punctures biopsy was more effective, for sextant
      biopsy failed to diagnose half of the cases of neoplasm. Three lateral punctures
      (basal, mid, and apical), with 2 additional punctures in the parasagittal midline
      (mid and apical) bilaterally are suggested as the best biopsy strategy.

PMID- 15745464
TI  - Diagnosis and treatment of prostatic abscess.
AB  - OBJECTIVES: Present and discuss the pathogenesis, diagnostic methods and
      treatment of the prostatic abscess. MATERIALS AND METHODS: We have
      retrospectively studied the medical records of 9 patients diagnosed and treated
      for prostatic abscess, between March 1998 and December 2000, assessing age,
      context, associated diseases, and diagnostic and therapeutic methods. We have
      compared the data found with those described in literature, based on Medline
      data. RESULTS: Mean age was 52.6 years. Three patients had previous diabetes
      mellitus diagnosis, and one was infected by HIV virus. Transrectal ultrasound of
      the prostate confirmed the diagnosis of prostatic abscess in all 7 cases in which
      it was performed. All cases received antibiotic treatment, and 77.8% needed
      concomitant surgical treatment. Two cases of microabscess were treated only with
      antibiotics. Four patients were submitted to perineal catheter drainage, 2 were
      submitted to transurethral resection of the prostate (TURP), and one patient
      required both procedures. Mean hospitalization time was 11.2 days, and most
      frequent bacterial agent was S. aureus. All patients were discharged from the
      hospital, and there was no death in this series. CONCLUSIONS: Prostatic abscess
      should be treated with broad-spectrum antibiotics and surgical drainage (perineal
      puncture or TURP). Microabscess may heal without surgery.

PMID- 15745465
TI  - Penile fracture - experience in 56 cases.
AB  - OBJECTIVE: The aim of this work is to report the diagnostic and therapeutic
      options for 55 patients with clinical diagnosis of penile fracture. MATERIAL AND
      METHODS: The patients were retrospectively assessed between 1982 and 2002. The
      primary diagnostic evaluation method for 55 patients (56 fractures) was clinical
      history and physical exam. Ten (17.8%) cases required complementary exams.
      Ultrasound (US) was performed in 2 cases, and magnetic resonance imaging (MRI) in
      1 case. Retrograde urethrocystogram was performed in suspicious urethral injury,
      which happened for 7 patients. RESULTS: Of 56 assessed cases, 49 (89.5%) were
      submitted to surgical exploration, and only 7 were conservatively conducted.
      Surgical treatment was performed in 48 patients (49 fractures), in these cases,
      47 (95.9%) presented tunica albuginea disruption and solely 2 (4.1%) evidenced
      lesion of dorsal vein. Ultrasonography confirmed disruption of tunica albuginea
      in 1 (50%) case, and in the other it was not possible to determinate the origin
      of the lesion, and the patient was submitted to surgical exploration, which
      confirmed the condition. MRI was used only in 1 case, confirming the lesion.
      Among 7 patients submitted to conservative management, until now, 3 (42.8%)
      required surgical intervention to correct penile chordee. CONCLUSIONS: Penile
      fracture is an entity of eminently clinical diagnosis, which management should be
      surgical and immediate, avoiding thus complications related to erectile
      dysfunction. When suspecting an associated urethral injury, Urethrocystogram is
      recommended. In cases where there is diagnostic uncertainty, ultrasound and/or
      MRI may be used to reveal the condition.

PMID- 15745466
TI  - Wilms' tumor in adults.
AB  - Wilms' tumor is an uncommon neoplasm in adults. We report the clinical
      manifestations, complementary explorations, treatment, and results from 3 males
      aged 16, 21, and 22 years. Computed tomography commonly suggests the diagnosis.
      Despite its aggressive treatment, such as radical surgery, chemo- and
      radiotherapy, the prognosis is worse than in children.

PMID- 15745467
TI  - Leiomyosarcoma of the renal vein.
AB  - Leiomyosarcoma of the renal vein is a rare tumor of complex diagnosis. We
      presented a case of renal vein leiomyosarcoma detected in a routine study. The
      primary treatment was complete surgical removal of the mass. In cases where
      surgical removal is not possible the prognosis is poor, with high rates of local
      recurrence and distant spread.

PMID- 15745468
TI  - Laparoscopic approach in the ovarian vein syndrome.
AB  - INTRODUCTION: The main objective of this article is to describe ureterolysis and
      ovarian vein resection laparoscopic technique. SURGICAL TECHNIQUE: With the
      patient in a 45o flank position, 3 trocars are used, 1 of 12 mm in the umbilicus
      for the optic passage, and 2 of 5 and 10 mm inserted in right hypochondrium and
      iliac fossa, respectively, for the forceps and stapler passage. The ureter and
      ovarian vein are identified after the mobilization of the colon. Both structures
      are dissected, with one ovarian vein segment is resected between metallic clips.
      COMMENTS: the ureteral approach by transperitoneal laparoscopy and colon
      mobilization facilitates its dissection, identify its relation to other
      structures, as well as making possible the concomitant treatment of gynecological
      diseases. For the ovarian syndrome treatment, ureterolysis and ovarian vein
      resection are performed, using only 3 trocars. Owing to its simplicity, low
      morbidity, and good results obtained, this procedure represents a good option for
      the surgical management of this syndrome.

PMID- 15745469
TI  - Use of cadaveric fascia lata to correct grade IV cystocele.
AB  - We describe a modification of the cadaveric prolapse repair and sling - CaPS
      technique that uses the sling surgery principles to correct grade IV cystocele.
      In this modification, the central and paravaginal defects reconstitution are
      performed using cadaveric fascia lata fixed over rectus abdominis muscle,
      eliminating the need of pubic fixation by screws, as proposed by the original
      technique. The modification described, besides presenting the benefits of CaPS,
      i.e., not using impaired tissues to reconstruct vesical support, and lower risks
      of perineal hypercorrection, also reduces the probability of complications of
      bone fixation.

PMID- 15745470
TI  - Surgical management of the neurogenic bladder and bowel.
AB  - Spina bifida and myelodysplasia are associated with neurogenic abnormalities of
      the bladder and bowel function. All children with myelodysplasia require an
      evaluation of their urinary tract with ultrasound and urodynamics to confirm
      normal bladder and kidney function. Patients with anatomical and functional
      abnormalities require treatment, the mainstay being intermittent catheterization
      and anticholinergic medication. The treatment goals for patients with a
      neurogenic bladder are the preservation of the upper urinary tract, bladder and
      bowel continence, independence, autonomy, and facilitation of self-esteem. A
      minority of children will not respond to conservative therapy and will ultimately
      require surgical intervention. This review will discuss the surgical options for
      bladder augmentation, bladder neck reconstruction and closure, as well as the
      methods for the creation of continent catheterizable stomas. The timing,
      indications, and description for each procedure will be addressed. Finally, the
      antegrade continence enema procedure will be described for the management of
      refractory fecal incontinence.

PMID- 15745471
TI  - Experimental model of bladder instability in rabbits.
AB  - OBJECTIVE: Propose a new experimental model of bladder instability in rabbits
      after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male
      rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g) were studied. The animals
      were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 -
      clinical control. In this group there was no surgical intervention; Group 2 -
      bladder outlet obstruction. In this group, after anesthetizing the animal,
      urethral cannulation with Foley catheter 10F was performed and then an adjustable
      plastic bracelet was passed around the bladder neck. It was then adjusted in
      order to not constrict the urethra. The following parameters were studied in M1 -
      pre-operative period; M2 - 4 weeks post-operatively moments: 1)- urine culture;
      2)- cystometric study; 3)- serum creatinine and BUN. RESULTS: Bladder weight was
      2.5 times larger in the group with obstruction than in the control group.
      Cystometric evaluation showed a significant increase in maximal vesical volume in
      the final moment at Group G2. However, there was no statistically significant
      difference among the groups studied. There was no statistically significant
      difference between maximal detrusor pressure and vesical compliance in the
      different moments or in the studied groups. There was an absence of uninhibited
      detrusor contractions in all the animals in group 1, and involuntary contractions
      were detected in 93% of group 2 animals. There was no significant variation in
      BUN and serum creatinine either among the groups or in the same group.
      CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5
      higher than normal bladders. We detected involuntary contractions in 93% of the
      animals in group 2, establishing this experimental model as appropriate to
      secondary bladder instability and partial bladder outlet obstruction.

PMID- 15745491
TI  - Surgical exploration of the injured kidney: current indications and techniques.
AB  - When treating renal injuries, the goals of the urologic surgeon are preservation
      of maximal renal function with a minimal risk of complications. To meet these,
      accurate staging is essential. The combined use of clinical and radiologic
      findings, with intra-operative information where available, will enhance the
      practitioner's ability to detect, classify, and treat renal injuries
      appropriately. We discuss our current approach to renal trauma and current
      indications and techniques for surgical exploration of the injured kidney.

PMID- 15745492
TI  - Assessment of stage T1 (TNM 1997) for renal cell carcinoma: is recommended the
      subdivision in T1a and T1b?
AB  - INTRODUCTION: Classification TNM 1997 defines renal cell carcinoma smaller than 7
      cm and confined to the kidney as stage T1. Our goal is to discuss if tumors
      smaller than 4 cm have the same behavior characteristics then tumors between 4
      and 7 cm, to compose the same stage of the disease. MATERIALS AND METHODS:
      Retrospective assessment of 138 patients in stage T1 (TNM - 97), divided into 2
      groups; group-1: composed of 65 patients (47%) with tumors < 4 cm, and group-2:
      composed of 73 patients (53%) with tumors between 4 and 7 cm. The following
      prognostic factors were assessed in the recurrence of the disease and survival of
      patients: nuclear degree, microvascular invasion, sarcomatous degeneration, and
      involved lymph nodes. Statistical evaluation has been accomplished through the
      log rank test, chi-square test, and Fisher's exact text. RESULTS: Average tumor
      size was 2.5 cm for group-1, and 5.3 cm for group-2. In group-2, there was the
      predominance of worse prognostic factors, with high-grade tumors (p = 0.01) and
      presence of microvascular invasion (p = 0.001). Sarcomatous tumors and
      involvement of lymph nodes did only happen in group-2. Disease-free survival for
      group-1, analyzed in the median period of 36 months, was 100%, and for group 2,
      in the median period of 31 months, was 81% (p = 0.008). CONCLUSION: The results
      obtained allow the conclusion that the present stage T1 for renal cell carcinoma
      gathers tumors of different evolution, being therefore recommendable the
      stratification in T1a for tumors smaller than 4 cm, and T1b for tumors between 4
      and 7 cm.

PMID- 15745493
TI  - Correlation between tumor extent in radical prostatectomies and preoperative PSA,
      histological grade, surgical margins, and extraprostatic extension: application
      of a new practical method for tumor extent evaluation.
AB  - PURPOSE: To evaluate a new method designed for estimating the tumor extent in
      radical prostatectomy specimens. The tumor extent was correlated to preoperative
      PSA and to several pathologic findings in the surgical specimens as well.
      MATERIALS AND METHODS: Tumor extent was estimated in 118 consecutive radical
      prostatectomies through a simple point-count method. Drawn on a sheet of paper,
      each quadrant of the whole mount sections contained 8 equidistant points. During
      the microscopic slides examination, the tumor area was drawn over the
      correspondent quadrant of the paper sheet. According to the extent, tumors were
      classified in 5 groups: 1) very limited: </= 10 positive points; 2) limited: 11
      19 positive points; 3) moderately extensive: 20-35 positive points; 4) extensive:
      36-39 positive points; 5) very extensive: 70 positive points. This classification
      was based on a previous analysis of tumor extent in 109 radical prostatectomies.
      The distribution was quite normal up to 69 positive points, but asymmetric above
      that number, including cases exceeding far above that value. We considered the
      quartiles of the normal distribution up to 69 positive points (groups 1 to 4),
      and above that value a fifth group was considered. RESULTS: There was a
      statistically significant and direct correlation between the tumor extent and all
      variables studied: preoperative PSA (p = 0.03), Gleason score (p < 0.0001),
      primary grade in high-grade tumors (p < 0.01), surgical margins (p < 0.0001),
      extraprostatic extension (pT3a) (p < 0.0001), and seminal vesicle invasion (pT3b)
      (p = 0.01). CONCLUSIONS: The method, which is simple and well correlated to other
      prognostic factors, is accessible to those pathologists working in routine
      pathology laboratories. Whether this method will be used by other urology centers
      is yet to be seen.

PMID- 15745494
TI  - Value of prostate specific antigen in predicting the existence of bone metastasis
      in scintigraphy.
AB  - OBJECTIVE: Evaluate the ability of serum concentration of prostate specific
      antigen (PSA) between 2 cutting points to predict the existence of bone
      metastasis confirmed by bone scintigraphy in man with prostate cancer. MATERIALS
      AND METHODS: Two hundred and fourteen consecutive patients with prostate cancer
      were evaluated during the present study in the period from 1998 to 2001. From all
      patients, PSA serum concentrations and bone scintigraphy were obtained. For the
      study, 2 cutting points of PSA (10 and 20 ng/mL) were adopted to predict the
      existence of bone metastasis. RESULTS: From the 214 patients, 35 (16.3 x 0025;)
      presented positive scintigraphic examinations for the presence of bone
      metastasis. No patient presented bone metastasis in scintigraphy if having PSA <
      10 ng/mL, and in only 1 patient (0.46 x 0025;) with bone metastasis PSA
      concentration was < 20 ng/mL. Therefore, when the cutting point adopted for PSA
      serum concentration was 10 ng/mL, a negative predictive value for bone metastasis
      was 100 x 0025; with sensitivity rates of 100%. Nevertheless, the positive
      predictive value and the specificity of the method were, respectively, 24.5 x
      0025; and 39.7 x 0025;. When the cutting point of PSA serum concentration was 20
      ng/mL, an increment was observed in rates of positive predictive value and
      specificity (41.5 x 0025; and 73.2 x 0025;), respectively, without substantial
      changes in negative predictive value (99.2 x 0025;) and sensitivity (97.1 x
      0025;) of the method. CONCLUSIONS: Data of present study allow for the conclusion
      that PSA serum concentration over 20 ng/mL was a more accurate cutting point than
      PSA serum concentration over 10 ng/mL to predict the presence of bone metastasis
      in scintigraphy.

PMID- 15745495
TI  - Economical impact of orchiectomy for advanced prostate cancer.
AB  - PURPOSE: To demonstrate the economical impact of surgical castration in
      comparison to the medical castration for patients with advanced prostate cancer.
      MATERIAL AND METHODS: Between January 2001 and December 2001, 32 patients with
      advanced prostate cancer underwent bilateral sub-capsular orchiectomy at our
      Hospital. The costs of this procedure were compared to the costs of medical
      castration with LH-RH analogues. RESULTS: The costs of the surgical procedure
      were extremely reduced when compared to published data on the medical treatment.
      Surgical castration did not have any stronger negative impact on the evolution of
      these patients when compared to medical castration. CONCLUSION: Surgical
      castration is an efficient and low cost treatment for advanced prostate cancer.

PMID- 15745496
TI  - Effects of the technique of cryopreservation and dilution/centrifugation after
      thawing on the motility and vitality of spermatozoa of oligoasthenozoospermic
      men.
AB  - OBJECTIVE: Comparing in human semen samples with low initial quality, the effects
      of 2 techniques of cryopreservation and dilution/centrifugation after thawing on
      the spermatic motility and vitality. MATERIALS AND METHODS: Semen samples from 15
      oligo and/or asthenozoospermic individuals assisted in the infertility sector of
      a tertiary hospital were obtained through masturbation. The samples were divided
      into 2 portions of equal volume, and diluted (1:1; v/v) with the cryoprotector
      containing glycerol (Test yolk buffer). One portion was frozen through the
      technique of liquid nitrogen vapor with static phases (group I - GI), while the
      other was frozen through a programmable biological freezer with linear speed
      (Planer, Kryo 10, series III) (group II - GII). The following parameters were
      assessed before freezing and after thawing: percentage of spermatozoa with
      progressive motility (Prog%) and percentage of live spermatozoa (Vit%). After
      defrosting, Prog% was assessed before and after removal of cryoprotector diluent,
      in different time intervals (zero, 3 h, and 24 h). The statistical analysis has
      been accomplished by using the non-parametric tests of Wilcoxon and Friedman.
      RESULTS: There was significant reduction of Prog% and Vit% from before freezing
      to after defrosting in both groups, I and II (p < 0.001). Values of Prog% and
      Vit% were not statistically different between groups, after thawing. It has been
      observed a significant reduction in Prog% among portions frozen with the
      automated technique after dilution and centrifugation for removal of
      cryoprotector (p = 0.006). After cryoprotector removal, Prog% has been kept
      unaltered, in both groups, during the first 3 hours of incubation, although being
      superior in group I (p = 0,04). There was a significant decrease in Prog% after
      24 hours of incubation, in both groups (p < 0,01). CONCLUSION: For human semen
      samples with low initial quality, freezing through vapor technique or through the
      automated technique showed to be equivalent in regarding recovery of live
      spermatozoa with progressive motility. The effects of dilution and centrifugation
      to remove the cryoprotector had a negative impact only in samples frozen through
      the automated technique. In both techniques, progressive motility is kept
      constant during the first 3 hours after thawing and removal of the cryoprotector,
      but is drastically diminished by the end of an incubation period of 24 hours.

PMID- 15745497
TI  - Percutaneous epididymal sperm aspiration (PESA) in men with obstructive
      azoospermia.
AB  - OBJECTIVES: Assessing the efficiency of repeated percutaneous epididymal sperm
      aspiration (PESA) in men with obstructive azoospermia, and also the possibility
      of cryopreservation of remaining material for future use in intracytoplasmic
      sperm injection (ICSI). METHOD: Retrospective study, in which 79 procedures of
      PESA were assessed in 58 patients (mean age = 45 years), whose partners had mean
      age of 34 years. Vasectomy was the most frequent cause of obstructive azoospermia
      (n = 46). RESULTS: Motile spermatozoa were obtained in 65 procedures (82%). PESA
      was twice repeated for 15 patients, 3 times for 5 patients, and 4 times for 1
      patient. Spermatozoa were found in 13 (87%) patients in the second attempt, in 4
      (80%) patients in the third attempt, and in the only patient that had
      accomplished 4 procedures. In 30 procedures (37%), we have obtained enough
      material for cryopreservation. In 12 among the 13 samples thawed (n = 13
      patients), motile spermatozoa were found, and ICSI was accomplished. Four
      patients that did not use their samples requested the elimination of the
      material. Total rate of pregnancy per transference was 21/55 (38%). In 14 PESA
      procedures, it was not possible to find spermatozoa; in these cases, the patients
      opted for accomplishing the procedure of testicular sperm aspiration (TESA).
      CONCLUSION: PESA is an efficient and simple method of retrieving spermatozoa,
      allowing repeated procedures. Additionally, spermatozoa collected through PESA
      can be cryopreserved.

PMID- 15745498
TI  - Thrombolytic therapy in bilateral embolism of renal arteries branches.
AB  - Bilateral renal artery embolism is rare, but it is a significant cause of
      arterial hypertension and renal failure, and most often is associated with
      cardiac arrhythmias. We report a case of bilateral renal artery embolism with a
      satisfactory outcome following use of thrombolytic therapy. A 42 year-old
      Caucasian man presented a sudden complaint of intense abdominal pain, in
      mesogastrium and left flank with dorsal irradiation, 3 days after electrical
      cardioversion due to cardiac arrhythmia. Laboratory tests revealed slight
      leukocytosis, hematuria, and creatinine of 1.8 mg/dL. Chest radiography was
      normal and computerized tomography showed an area of massive ischemia in left
      kidney, and focal ischemia in right kidney and spleen. The patient was then
      submitted to systemic venous therapy with 1.5 million units of streptokinase,
      with an excellent outcome.

PMID- 15745499
TI  - Vesical hemangioma in patient with Klippel-Trenaunay-Weber syndrome.
AB  - Klippel-Trenaunay-Weber syndrome is characterized by cutaneous hemangiomas,
      varicosity and bony hypertrophy of extremities. Urinary tract hemangiomas may
      occur in 3 to 6% of these patients. This work intends to report a case of a
      patient with a huge vesical hemangioma, who presented this syndrome. A 5 year-old
      boy with Klippel syndrome sought our services due to 3 episodes of gross
      hematuria in the past 30 days. Excretory urography and computerized tomography
      were performed, indicating the presence of a swelling in vesical dome. An
      exploratory cystotomy was conducted and the dark colored mass in vesical dome was
      excised by partial cystectomy. The histopathologic finding confirmed that it was
      a vesical hemangioma. Though rare, urinary tract hemangiomas must always be
      considered in patients with Klippel-Trenaunay syndrome.

PMID- 15745500
TI  - Percutaneous renal surgery--new model for learning and training.
AB  - INTRODUCTION: Aiming at promoting and facilitating learning and training in
      percutaneous renal surgery, we have created an easy to assemble, reproducible and
      cheap laboratory model. The model was built using pig kidney, foam layer, plastic
      catheter, linen or cotton holding sutures, and wide scotch tape. SURGICAL
      TECHNIQUE: The kidney with catheterized ureter is fixed and involved in a foam
      layer. It stays hidden, and is visible only through radioscopy. This model is
      positioned and fixed to a radiological table in such a way that it simulates the
      patient's lumbar region. After that, contrast medium is injected through the
      ureter, and the urinary system is examined through radioscopy. All percutaneous
      maneuvers can be accomplished, from the puncture, tract dilation, insertion of
      Amplatz sheath, and introduction of nephroscope, allowing lithotripsy and
      endopielotomy, as well as other types of percutaneous surgeries. COMMENTS: The
      great advantage of this model is its easy construction, by using very cheap and
      widely available material. Foam can be several times washed and reused. After
      treatment, the model can be immediately open, and a critical analysis can be
      made, being then possible to verify if the place of renal puncture was well
      chosen, if dilation was correctly accomplished, and if the collecting system has
      been preserved. Therefore, this model can represent a great advance for the
      learning and training in percutaneous surgery.

PMID- 15745501
TI  - Bulbar urethroplasty using the dorsal approach: current techniques.
AB  - INTRODUCTION: The use of flaps or grafts is mandatory in patients with longer and
      complex strictures. In 1995-96 we described a new dorsal onlay graft
      urethroplasty. Over time, our original technique was better defined and changed.
      Now this procedure (also named Barbagli technique) has been greeted with a fair
      amount of enthusiasm in Europe and in the United States. SURGICAL TECHNIQUE: The
      patient is placed in normal lithotomy position, and a midline perineo-scrotal
      incision is made. The bulbar urethra is then free from the bulbo-cavernous
      muscles, and is dissected from the corpora cavernosa. The urethra is completely
      mobilized from the corpora cavernosa, it is rotated 180 degrees, and is incised
      along its dorsal surface. The graft (preputial skin or buccal mucosa) or the flap
      is fixed and quilted to the tunica albuginea of the corporal bodies. The right
      mucosal margin of the opened urethra is sutured to the right side of the patch
      graft. The urethra is rotated back into its original position. The left urethral
      margin is sutured to the left side of the patch graft and to the corporal bodies,
      and the grafted area is entirely covered by the urethral plate. The bulbo
      cavernous muscles are approximated over the grafted area. A 16F silicone Foley
      catheter is left in place. COMMENTS: Dorsal onlay graft urethroplasty is a
      versatile procedure that may be combined with various substitute materials like
      preputial skin, buccal mucosa grafts or pedicled flaps.

PMID- 15745502
TI  - Modulation of urethral alpha-sympathetic by parasympathetic before and following
      bethanechol chloride injection.
AB  - INTRODUCTION AND OBJECTIVES: Chagas' disease causes specific parasympathetic
      denervation and in its digestive clinic form promotes also functional alterations
      in bladder. Thus, the aim was to investigate the existence of balance between
      sympathetic and parasympathetic systems in lower urinary tract, as occurs in
      other organs. We verified the urethral closing pressure before and following
      parasympathetic stimulus. PATIENTS AND METHODS: For that, the urethral closure
      pressure was studied before and after the injection of 5 mg of bethanechol
      chloride subcutaneously in 28 voluntary female patients, divided into 4 groups.
      The constitution of theses groups was: A) normal control = 6 patients; B) Chagas'
      disease with positive serology only = 5 patients; C) Chagas' disease with cardiac
      disease = 6 patients, and D) Chagas' disease with digestive disease and vesical
      hyporeflexia = 11 patients. Urethral profilometry was performed through perfusion
      urethral catheter with a 6.5 ml/minute flow and a traction rate of 5 mm/minute.
      RESULTS: Means and standard deviations for urethral closure pressure before
      bethanechol chloride were respectively: group A = 67.3 +/- 7.1; group B = 69.2 +/
      7.4; group C = 95.8 +/- 5.1; group D = 82.1 +/- 8.4. After bethanechol chloride
      they were: group A = 66.0 +/- 6.6; group B = 77.0 +/- 7.6; group C = 98.3 +/-
      8.8; group D = 45.9 +/- 6.2. The Kruskal Wallis statistical test did not show
      statistically significance difference between groups A, B, C. However, it was
      statistically significant between groups C and D with p = 0.003. Wilcoxon test
      showed p = 0.001, only for values in group D before and following bethanechol
      chloride. CONCLUSIONS: Chagas' disease in its intestinal form seems to alter
      urethral function as well. Parasympathetic stimulation decreased urethral
      pressure, indicating potential modulation by the parasympathetic system over the
      sympathetic system.

PMID- 15745503
TI  - Effect of vitamin C supplements on urinary oxalate and pH in calcium stone
      forming patients.

PMID- 15745504
TI  - Pediatric staghorn calculi: the role of extracorporeal shock wave lithotripsy
      monotherapy with special reference to ureteral stenting.

PMID- 15745505
TI  - Hand-assisted laparoscopy for large renal specimens: a multi-institutional study.

PMID- 15745506
TI  - Prospective comparison of short-term convalescence: laparoscopic radical
      prostatectomy versus open radical retropubic prostatectomy.

PMID- 15745508
TI  - pT1 Substaging in renal cell carcinoma: validation of the 2002 TNM staging
      modification of renal tumors.

PMID- 15745507
TI  - Follow up of high grade prostatic intraepithelial neoplasia and atypical small
      acinar proliferation in a highly screened patient population.

PMID- 15745509
TI  - The urethra and its supporting structures in women with stress urinary
      incontinence: MR imaging using an endovaginal coil.

PMID- 15745510
TI  - Incidence of malignancy in complex cystic renal masses (Bosniak category III):
      should imaging-guided biopsy precede surgery?

PMID- 15745511
TI  - Effect of botulinum toxin A on the autonomic nervous system of the rat lower
      urinary tract.

PMID- 15745512
TI  - Nitric oxide synthase in the external urethral sphincter of the sheep:
      immunohistochemical and functional study.

PMID- 15745513
TI  - Free neurovascular transfer of latissimus dorsi muscle for the treatment of
      bladder acontractility: II. Clinical results.

PMID- 15745514
TI  - Comparison of clinical and urodynamic outcome in orthotopic ileocaecal and ileal
      neobladder.

PMID- 15745515
TI  - The value of a second transurethral resection in evaluating patients with bladder
      tumours.

PMID- 15745516
TI  - A study of the morbidity, mortality and long-term survival following radical
      cystectomy and radical radiotherapy in the treatment of invasive bladder cancer
      in Yorkshire.

PMID- 15745517
TI  - The urologist's guide to genital piercing.

PMID- 15745518
TI  - Incontinent ileovesicostomy in the management of neurogenic bladder dysfunction.

PMID- 15745520
TI  - Natural history of neonatal reflux associated with prenatal hydronephrosis: long
      term results of a prospective study.

PMID- 15745519
TI  - A preliminary investigation into quality of life, psychological distress and
      social competence in children with cloacal exstrophy.

PMID- 15745522
TI  - Renal pelvic stones: choosing shock wave lithotripsy or percutaneous
      nephrolithotomy.
AB  - Introduction of minimally invasive techniques has revolutionized the surgical
      management of renal calculi. Extracorporeal shock wave lithotripsy and
      percutaneous nephrolithotomy are now both well-established procedures. Each
      modality has advantages and disadvantages, and the application of each should be
      based on well-defined factors. These variables include stone factors such as
      number, size, and composition; factors related to the stone's environment,
      including the stone's location, spatial anatomy of the renal collecting system,
      presence of hydronephrosis, and other anatomic variables, such as the presence of
      calyceal diverticula and renal anomalies; and clinical or patient factors like
      morbid obesity, the presence of a solitary kidney, and renal insufficiency. The
      morbidity of each procedure in relation to its efficacy should be taken in to
      account. This article will review current knowledge and suggest an algorithm for
      the rational management of renal calculi with shock wave lithotripsy and
      percutaneous nephrolithotomy.

PMID- 15745523
TI  - Radiological classification of renal angiomyolipomas based on 127 tumors.
AB  - PURPOSE: Demonstrate radiological findings of 127 angiomyolipomas (AMLs) and
      propose a classification based on the radiological evidence of fat. MATERIALS AND
      METHODS: The imaging findings of 85 consecutive patients with AMLs: isolated (n =
      73), multiple without tuberous sclerosis (TS) (n = 4) and multiple with TS (n =
      8), were retrospectively reviewed. Eighteen AMLs (14%) presented with hemorrhage.
      All patients were submitted to a dedicated helical CT or magnetic resonance
      studies. All hemorrhagic and non-hemorrhagic lesions were grouped together since
      our objective was to analyze the presence of detectable fat. Out of 85 patients,
      53 were monitored and 32 were treated surgically due to large perirenal component
      (n = 13), hemorrhage (n = 11) and impossibility of an adequate preoperative
      characterization (n = 8). There was not a case of renal cell carcinoma (RCC) with
      fat component in this group of patients. RESULTS: Based on the presence and
      amount of detectable fat within the lesion, AMLs were classified in 4 distinct
      radiological patterns: Pattern-I, predominantly fatty (usually less than 2 cm in
      diameter and intrarenal): 54%; Pattern-II, partially fatty (intrarenal or
      exophytic): 29%; Pattern-III, minimally fatty (most exophytic and perirenal):
      11%; and Pattern-IV, without fat (most exophytic and perirenal): 6%. CONCLUSIONS:
      This proposed classification might be useful to understand the imaging
      manifestations of AMLs, their differential diagnosis and determine when further
      radiological evaluation would be necessary. Small (< 1.5 cm), pattern-I AMLs tend
      to be intra-renal, homogeneous and predominantly fatty. As they grow they tend to
      be partially or completely exophytic and heterogeneous (patterns II and III). The
      rare pattern-IV AMLs, however, can be small or large, intra-renal or exophytic
      but are always homogeneous and hyperdense mass. Since no renal cell carcinoma was
      found in our series, from an evidence-based practice, all renal mass with
      detectable fat should be considered an AML.

PMID- 15745524
TI  - Metabolic investigation of patients with urolithiasis in a specific region.
AB  - OBJECTIVE: To assess the prevalence of the main metabolic alterations found in
      patients with recent diagnosis of urolithiasis in the West region of Parana
      state, Brazil. MATERIALS AND METHODS: We made a retrospective study on 425
      patients with evidence of recent formation of renal stones. Laboratory assessment
      consisted in 3 samples of 24-hour urine with dosing of calcium, uric acid,
      citrate, oxalate, sodium and creatinine. A urine culture was also made and
      qualitative cystinuria and urinary pH following 12-hour fasting and water
      restriction were evaluated. RESULTS: In 96.5% of patients a cause was detected
      for the urolithiasis. Metabolic alterations most frequently found were:
      hypercalciuria (38.3%), hypocitraturia (29.6%) and hyperexcretion of uric acid
      (21.6%). Low urinary volume (17.9%), urinary tract infection (12.9%),
      hyperparathyroidism (3.3%), renal tubular acidosis (1.2%), cystinuria (0.9%) and
      anatomical alterations (12.7%) were also observed. CONCLUSIONS: Hypercalciuria,
      hypocitraturia and hyperuricuria are the most frequent metabolic disorders in the
      population under study and these data are in accordance to the literature.

PMID- 15745525
TI  - Rupture of vesicourethral anastomosis following radical retropubic prostatectomy.
AB  - OBJECTIVE: Rupture of vesicourethral anastomosis following radical retropubic
      prostatectomy is a complication that requires immediate management. We evaluated
      the morbidity of this rare complication. MATERIALS AND METHODS: We analyzed
      retrospectively 5 cases of disruption of vesicourethral anastomosis during post
      operative period in a consecutive series of 1,600 radical retropubic
      prostatectomies, performed by a single surgeon. RESULTS: It occurred in a ratio
      of 1:320 prostatectomies (0,3%). Management was conservative in all the cases
      with an average catheter permanence time of 28 days, being its removal preceded
      by cystography. Two cases were secondary to bleeding, 1 followed the change of
      vesical catheter and 2 by unknown causes after removing the Foley catheter. Only
      one patient evolved with urethral stenosis, in the period ranging from 6 to 120
      months. CONCLUSION: Rupture of vesicourethral anastomosis is not related to the
      surgeon's experience, and conservative treatment has shown to be effective.

PMID- 15745526
TI  - Clodronate for treatment of bone metastases in hormone refractory prostate
      cancer.
AB  - INTRODUCTION: Approximately 85% of patients who die from prostate cancer have
      bone metastases. Even though the radiological aspect of such metastases is
      osteoblastic, we currently know that these lesions are mixed, with coexisting
      blastic and lytic lesions, always beginning with bone lysis by osteoclast
      proliferation. Treatment options are palliative and have poor response, and when
      there is an improvement it is usually short-lived. This work intends to study the
      effect of clodronate in the treatment of skeletal complications of prostate
      cancer. MATERIALS AND METHODS: In an open prospective study 32 patients with
      hormone refractory prostate cancer with metastases to bones were assessed, in the
      period between November 2000 and September 2002. Mean age was 69 years (51 to 83
      years). Patients were previously assessed by a pain scale and Karnofsky index.
      They underwent bone scintigraphy, X-ray, dosage of prostate specific antigen
      (PSA) and biochemical tests before and following treatment (administration of
      intravenous clodronate every 28 days). The Student's t-test was used for
      statistical analysis. RESULTS: Twenty-nine patients (90.6%) showed improvement
      after the first and the 2nd cycles, which persisted for at least 4 months.
      Average on the pain scale improved from 7.7 to 2.1 and Karnofsky index raised
      from 42 to 71. Radiological aspect of the metastases improved in 15 patients
      (46.8%) and side effects were low (only 2 patients - 6.2%). CONCLUSION:
      Bisphosphonate was effective in the treatment of skeletal complications of
      prostate cancer, presenting an objective response in 90.6% of treated patients,
      with a marked improvement in the pain scale, Karnofsky index and consequently in
      the quality of life of patients, and with low side effects.

PMID- 15745527
TI  - Estimated costs of treatment of benign prostate hyperplasia in Brazil.
AB  - INTRODUCTION: The treatment of benign prostate hyperplasia (BPH) presents 2
      options: medical or surgical, and there are doubts about what is the best
      treatment since 80% of patients who undergo surgery become asymptomatic and 10 to
      40% of those under medical regimen undergo surgery within a 5 years period. It is
      difficult to assess the actual costs of treating BPH in Brazil due to several
      factors, among them regional particularities and the scarcity of current
      statistical data. PATIENTS AND METHODS: Recently, in the Ribeirao Preto area, Sao
      Paulo, Brazil, the IPSS (International Prostatic Symptoms Score) and quality of
      life were verified in 934 volunteers. It was determined the percentage of
      individuals with ages ranging from 40 to 79 years with moderate symptoms (score 8
      19) and with severe symptoms (score 20-35), values for which are indicated
      medical and surgical treatment, respectively, according to the Brazilian Society
      of Urology consensus on BPH. Data on Brazilian population in that age range were
      obtained from the Brazilian Institute of Geography and Statistics referent to the
      year of 2000. It was determined the number of patients, according to the criteria
      above, subjected to either one of the treatments mentioned. Surgical costs of
      prostate transurethral resection were researched according to Unified Health
      System - SUS tables (173 US dollars) and of Brazilian Medical Society - AMB with
      a mean cost in 3 hospitals of 933 US dollars. Drug costs were calculated by the
      annual mean price (355 US dollars) of 4 alpha-blockers (tamsulosin, alfuzosin,
      doxazosin and terazosin). RESULTS: The estimated population for medical treatment
      was 5,397,321 individuals, with a cost corresponding to 1,916,489,055.00 US
      dollars. The estimated population for surgical treatment was 2,040,299 men, what
      would represent a cost of 353,291,204.00 US dollars based on the SUS table and of
      1,904,279,066.00 US dollars based on AMB with hospital expenses included.
      CONCLUSION: All theses facts induce us to predict that the treatment of BPH in a
      not-so-far future can become a public health problem for Brazilian society, since
      the current estimate would be, approximately, costs around 2.26 - 3.83 billion
      dollars, added by the yearly increase in the risk population (24.99%) for the
      group under medical treatment and over the non-operated amount of the surgical
      group.

PMID- 15745528
TI  - Surgical treatment of metachronous metastases in different organs following
      radical nephrectomy.
AB  - Renal clear cell carcinoma (RCCC) is a neoplasia resistant to radio and
      chemotherapy, with surgical treatment being the procedure that is recognized for
      its curative treatment. This case report demonstrates the success of an
      aggressive surgical treatment for consecutive and late metachronous metastases
      following radical nephrectomy. CASE REPORT: Asymptomatic 50-year old man. During
      a routine examination, an incidental mass was found by renal ultrasonography. He
      underwent right radical nephrectomy due to RCCC in June 1992. During the follow
      up metastases were evidenced in cerebellum on the seventh year, and in left lung
      and pancreas on the eighth year following the radical nephrectomy, with all of
      them successfully treated by surgical excision. COMMENTS: The surgical excision
      of consecutive and late metachronous metastases in different organs arising from
      RCCC is feasible, being a good therapeutic alternative in selected cases.

PMID- 15745529
TI  - Nephrobronchial fistula secondary to xantogranulomatous pyelonephritis.
AB  - INTRODUCTION: Nephrobronchial fistula is a rare complication of
      xanthogranulomatous pyelonephritis, a disease that can fistulize to lungs, skin,
      colon and other organs. CASE REPORT: A 37-year old patient presented a chronic
      history of lumbar pain and thoracic symptoms such as cough, dyspnea and oral
      elimination of pus. Patient went to several services and was submitted to 2
      thorax surgeries before definitive treatment (nephrectomy) was indicated. After
      nephrectomy, the patient presented an immediate improvement with weight gain (8
      kg / 1 month) and all his symptoms disappeared. CONCLUSION: This clinical case
      illustrates the natural history of nephrobronchial fistula, the importance of
      clinical history for diagnosis and the relevance of early treatment of renal
      lithiasis.

PMID- 15745530
TI  - Bilateral hydronephrosis caused by vaginal prolapse.
AB  - INTRODUCTION: Even though it is uncommon, uterine prolapse can cause compression
      of ureters and bilateral hydronephrosis, predisposing to arterial hypertension
      and renal failure. Hydronephrosis consequent to cystocele and to vaginal prolapse
      is even rarer. CASE REPORT: This paper reports on a 59 year-old patient,
      Caucasian, obese and hysterectomized who presented complete vaginal prolapse with
      bilateral hydronephrosis and slight alteration in serum urea and creatinine.
      Patient underwent correction of vaginal prolapse by endoscopic suspension
      technique with improvement of hydronephrosis and normalization of renal function.
      This work emphasizes the rarity of such case and the requirement of surgical
      approach.

PMID- 15745531
TI  - Intramural leiomyomas of the bladder in asymptomatic men.
AB  - Bladder leiomyomas are rare benign mesenchymal tumors, which account for less
      than 0.43% of all bladder tumors with approximately 200 cases described in the
      literature. These tumors may be classified into 3 different locations:
      endovesical, intramural and extravesical. Endovesical is the most common form,
      accounting for 63-86% of the cases, while intramural occurs in 3-7% and
      extravesical in 11-30%. The intramural form, especially small tumors, may not
      produce symptoms hardening detection. We report two cases of intramural bladder
      leiomyomas in asymptomatic men observed incidentally by transabdominal
      ultrasonography during the follow-up of benign prostatic hyperplasia. We discuss
      the diagnosis and management of these lesions.

PMID- 15745532
TI  - Magnetic resonance in diagnosis of ureterocele.
AB  - Ultrasonography is the main non-invasive technique for screening of ureterocele,
      but presents some difficulties for its diagnosis. Other supplementary diagnostic
      methods have the disadvantage of being invasive or using ionizing radiation.
      Magnetic resonance (MR) has a high sensitivity for diagnosing urinary tract
      malformations in adults and children. We report one case of ureterocele in a 1
      year old child with the purpose of presenting its diagnosis through MR.

PMID- 15745533
TI  - Transurethral microwave thermotherapy for benign prostatic hyperplasia.
AB  - Transurethral resection of the prostate (TURP) remains the gold standard for
      treatment of benign prostatic hyperplasia (BPH). In general, while this procedure
      is safe, patients require a spinal, epidural, or general anesthesia and often
      several days of hospital stay; the potential morbidity and mortality limits the
      use of TURP in high-risk patients. Pharmacotherapy has been recommended as a
      first-line therapy for all patients with mild to moderate symptoms. Patients are
      often times enthusiastic if they are offered a one-time method to treat lower
      urinary tract symptoms secondary to BPH, provided that the method offers reduced
      risk and allows an efficacy equal to that of medical therapy. One such method is
      transurethral microwave thermotherapy (TUMT). TUMT involves the insertion of a
      specially designed urinary catheter with a microwave antenna, which heats the
      prostate and destroys hyperplastic prostate tissue. TUMT allows the avoidance of
      general or regional anesthesia, and results in minimal blood loss and fluid
      absorption. In this review, the authors discussed the current indications and
      outcome of TUMT, including the history of the procedure, the mechanism of action,
      the indications for TUMT, the pre-operative considerations, the patient
      selection, the results in terms of efficacy, by comparing TUMT vs. Sham, TUMT vs.
      Alpha-blocker and TUMT vs. TURP. Finally, the complications are presented, as
      well as other uses and future directions of the procedure. The authors concluded
      that TUMT is a safe and effective minimally invasive alternative to treatment of
      symptomatic BPH.

PMID- 15745551
TI  - Case selection and outcome of radical perineal prostatectomy in localized
      prostate cancer.
AB  - Radical prostatectomy continues to play a central role in the management of
      localized prostate cancer. The majority of patients diagnosed with prostate
      cancer will undergo radical prostatectomy. A decrease in the morbidity of this
      surgical procedure has been accomplished through an improved understanding of
      pelvic anatomy and a greater understanding of the natural history of prostate
      cancer. Recently, minimally invasive techniques have been applied to radical
      prostatectomy (laparoscopic prostatectomy) in order to further decrease the
      morbidity of this operation. What remains to be determined is whether this
      approach confers the same long term surgical outcomes as the open approach. One
      method which offers known long term outcomes coupled with decreased morbidity is
      the radical perineal prostatectomy. The purpose of this paper is to review the
      criteria for patient selection as well as outcomes of the radical perineal
      prostatectomy.

PMID- 15745552
TI  - Racial influence on the prevalence of prostate carcinoma in Brazilian volunteers.
AB  - PURPOSE: To investigate the prevalence of prostate carcinoma in a sample of
      volunteers known to have a large proportion of Bantu African ancestors, and the
      performance of total PSA (tPSA), PSA density (PSAD) and free-to-total PSA ratio
      (f/tPSA) on the diagnosis. MATERIALS AND METHODS: A total of 473 volunteers
      (range: 40 - 79 years) were screened for prostate carcinoma. Those with tPSA >2
      ng/ml and/or abnormal digital rectal examination were submitted to a transrectal
      ultrasound-directed biopsy (10 cores). The volunteers were classified as White,
      Mulatto or Black according to physical characteristics and to ancestors race
      reference. The following variable number of tandem repeats (VNTR) were analyzed
      in the blood of 120 volunteers without cancer and in 27 patients with prostate
      cancer: D4S43, PAH, F13A1, APOB and vW-1. RESULTS: The biopsies performed in 121
      volunteers revealed cancer in 27 (5.7% of 473). The proportions of cancer in
      White, Mulatto and Black were respectively: 0.6% (1/148), 6.7% (6/90) and 8.5%
      (20/235) (p = 0.006). The VNTRs analysis revealed heterogeneity in White, Mulatto
      and Black anthropologic phenotypes with the following admixture of Caucasian,
      African and Amerindian gene lineages: 67.5 +/- 8%, 20.8 +/- 8%, 11.7 +/- 7%; 54.8
      +/- 9%, 36.3 +/- 5%, 8.9 +/- 7%; and, 45.3 +/- 3%, 45.9 +/- 4%, 8.8 +/-7%. Such a
      mixture was 50.5 +/- 9%, 49 +/- 8% and 0.5 +/- 4% in volunteers bearing cancer,
      and 59.1 +/- 7%, 31.7 +/- 8% and 9.2 +/- 5% in those without cancer. The
      sensitivity and specificity of tPSA at cut-off levels of 2, 2.5 and 4 ng/ml for
      volunteers with tPSA </= 10 ng/ml were respectively: 100% and 6,6%, 100% and
      36,6%, 69,2% and 62,2%. PSAD at a cut-off level of 0.08 or 0.10, and f/tPSA at a
      cut-off level of 20% were able to increase significantly tPSA specificity without
      loss on sensitivity. CONCLUSIONS: The tumor prevalence was higher in Non-White
      than in White phenotype. The association of tPSA at a cut-off level of 2.5 ng/ml
      with a PSAD of 0.08 or a f/tPSA of 20% for biopsy indication deserves further
      investigations as an alternative to tPSA cut-off level of 4 ng/ml.

PMID- 15745553
TI  - Prevalence of prostate adenocarcinoma according to race in an university
      hospital.
AB  - OBJECTIVES: To determine the prevalence of prostate cancer and to assess
      potential associations between race and prostate adenocarcinoma according to age
      in patients followed in an outpatient service of general urology in an university
      hospital. MATERIALS AND METHODS: Retrospective study of men aged from 40 to 79
      years, followed during the period from 1999 to 2001. Patients were classified
      according to race in White, Mulatto and Black. Those with abnormal digital rectal
      examination and/or serum level of prostate specific antigen (PSA) > 4.0 ng/ml,
      underwent a transrectal prostate biopsy. RESULTS: 580 patients with mean age of
      60.7 +/- 10.0 years were studied, with 116 Whites (20.0%), 276 Mulattos (47.6%)
      and 188 Blacks (32.4%). There was no significant difference regarding the mean
      age (p = 0.62), serum level of PSA (p = 0.65) and prevalence of prostate
      adenocarcinoma between Whites, Mulattos and Blacks (p = 0.36). While studying the
      association between race classified in 2 groups (Whites versus Mulattos and
      Blacks) and prostate adenocarcinoma according to age, no association was found
      when the total group was assessed, neither among those with age above 60 years
      old. In the group between 40 and 60 years, even though without statistical
      significance, the estimate of prevalence ratio was 2.2 (CI 95%: 0.52 to 9.0; p =
      0.38). CONCLUSION: Prostate adenocarcinoma was found in 16.6% of the patients
      aged between 40 and 79 years. We did not find a racial influence in our
      population.

PMID- 15745554
TI  - Antibiotic prophylaxis in prostate biopsy. A comparative randomized clinical
      assay between ciprofloxacin, norfloxacin and chloramphenicol.
AB  - OBJECTIVE: To compare, prospectively, 4 different schemes of antibiotic
      prophylaxis previously to transrectal prostate biopsy. MATERIALS AND METHODS: 257
      patients were randomized in 4 groups: Group I: single dose of ciprofloxacin 2
      hours before the procedure; Group II: ciprofloxacin 3 days; Group III:
      chloramphenicol 3 days; and Group IV: norfloxacin 3 days. The complication rate
      was assessed in a blind way on the third and on the thirtieth days through a
      questionnaire. Groups were compared by the qui-square method and, in small
      samples, by the Fisher method, with statistical significance of 95%. RESULTS:
      Complications index throughout the sample differed between the 4 groups of
      patients under study, being 3.1% for group I, 2.1%for group II, 18.3% for group
      III and 10.5% for group IV. Schemes employing ciprofloxacin were statistically
      superior to those that used norfloxacin or chloramphenicol (p < 0.05). There was
      no difference between a single dose and 3 days of ciprofloxacin (p > 0.05).
      CONCLUSION: Schemes using ciprofloxacin presented better results in prophylaxis
      previously to prostate biopsy. We recommend using a single dose of ciprofloxacin
      due to its posologic ease and low cost, associated with a therapeutic response
      equivalent to 3-day regimens.

PMID- 15745555
TI  - Effect of sildenafil in cavernous arteries of patients with erectile dysfunction.
AB  - INTRODUCTION: Sildenafil citrate is a type 5 phosphodiesterase inhibitor, which
      has demonstrated excellent results in the treatment of erectile dysfunction. The
      effect of sildenafil citrate in the cavernous arteries of patients with erectile
      dysfunction has not been established yet. The objective of this study was to
      assess the effect of sildenafil citrate in the cavernous arteries of patients
      with erectile dysfunction, following an intracavernous injection of alprostadil.
      MATERIALS AND METHODS: 29 male patients, with mean age of 53.8 years (32 to 75
      years), were prospectively evaluated. The mean time with complaint of erectile
      dysfunction was 50.5 months (6 to 168 months). Each patient was his own control.
      Patients underwent a measurement of peak systolic velocity before and after use
      of sildenafil citrate associated with 5 micrograms of alprostadil, through
      ultrasonic velocitometry Knoll/MIDUS system. In the interval between
      measurements, approximately 15 days, patients used 3 tablets of sildenafil at
      home with their partners. RESULTS: Using only 5 mcg of alprostadil, average peak
      systolic velocity was 23.9 cm/s, and when associated to 50 mg of sildenafil it
      was 24.8 cm/s. Despite the increase in the flow rate caused by sildenafil, the
      difference was not statistically significant, Z calculated = - 0.695 NS (Wilcoxon
      test). Twenty one of the 29 patients (72.4%) showed global improvement in sexual
      performance with the use of sildenafil citrate at home. There was not a
      statistically significant correlation between the global response to sildenafil
      citrate and the increase in the peak systolic velocity. CONCLUSION: We concluded
      that, even though the use of 50 mg of sildenafil citrate associated with 5 mcg of
      alprostadil provides an increase in the peak systolic velocity of the cavernous
      arteries, there was no statistic difference in relation to alprostadil alone.
      There was no correlation between the global response to sildenafil and the
      increase in the peak systolic velocity.

PMID- 15745556
TI  - Chronic penile strangulation.
AB  - Chronic penile strangulation is exceedingly rare with only 5 cases previously
      reported. We report an additional case of progressive penile lymphedema due to
      chronic intermittent strangulation caused by a rubber band applied to the penile
      base for 6 years. A 49-year-old man presented incapacity to exteriorize the glans
      penis. For erotic purposes, he had been using a rubber-enlarging band placed in
      the penile base for 6 years. With chronic use, he noticed that his penis swelled.
      Physical examination revealed lymphedema of the penis, phimosis and a stricture
      in the penile base. The patient was submitted to circumcision and the lymphedema
      remained stable 10 months postoperatively. Chronic penile incarceration usually
      causes penile lymphedema and urinary disturbance. Treatment consists of removal
      of foreign devices and surgical treatment of lymphedema.

PMID- 15745557
TI  - Bilateral and synchronic seminomatous testicular neoplasia.
AB  - Testicular neoplasia is rare, especially when it is bilateral, and even more when
      it is synchronic, with its incidence being only 0.17% of germinative tumors of
      testicles. We present here the case of a male, 32-year old patient, without
      children. Patient underwent a bilateral radical orchiectomy, following previous
      sperm harvest, in a sperm bank. Surgery was performed in 2 stages, with a 12-day
      interval, with implantation of a silicone testicular prosthesis. The result of
      anatomicopathological examination revealed bilateral classical seminoma, pT2 on
      the right side and T1 on the left. He was submitted to bilateral complementary
      radiotherapy, with 2,500 cGy on each side. Patient had a good outcome from a
      medical and oncologic perspective, but a follow-up with psychotherapy was needed.

PMID- 15745558
TI  - Slightly modified technique of the original Essed plication procedure for
      congenital penile deviation.
AB  - PURPOSE: The Schroeder-Essed plication procedure is a standard technique for the
      correction of penile curvature. In a retrospective analysis we compared
      functional results and quality of life (LQ) of the original technique with
      inverted sutures as described by Schroeder-Essed and our slight modification
      consisting of horizontal incisions into the tunica albuginea. MATERIALS AND
      METHODS: Twenty-six patients with congenital penis deviation were treated for
      penile deviation by the original Schroeder-Essed plication with inverted sutures
      (11 patients) and by the described modification (15 patients). In case of
      modified technique, horizontal and parallel incisions 4 mm to 6 mm apart and
      about 8 mm - 10 mm long were made through the tunica albuginea. The outer edges
      of the incisions were then approximated with permanent inverted sutures (Gore-Tex
      3-0). Mean age was 21.6 years in the first group and 23.2 years in the second
      group. Average follow-up was 28 months and 13 months, respectively. The
      preoperative penile deviation angle was > 25 degrees in all patients without
      difference between the 2 groups. RESULTS: All patients in both groups reported an
      improvement in their quality of life and full ability to engage in sexual
      intercourse. Nine patients (88%) in the first group and 14 patients (93%) in the
      second group were satisfied with the cosmetic result. In contrast, 10 patients
      (91%) of the first and 13 patients (87%) of the second group complained of penile
      shorting. Recurrence of deviation was only noticed in 2 males in the first group
      (18%). CONCLUSIONS: Our results indicate that this simple modification of the
      Schroeder-Essed plication offers good functional and cosmetic results. Most
      patients were satisfied with the penile angle correction results.

PMID- 15745559
TI  - Radical cystectomy with preservation of sexual function and urinary continence:
      description of a new technique.
AB  - OBJECTIVE: To describe the original cystoprostatectomy technique which allows the
      preservation of sexual and urinary function in the majority of treated patients.
      SURGICAL TECHNIQUE: The described technique presents some details that
      distinguish it from classic cystectomy: 1) a more efficient control of prostate
      venous and arterial tributaries; 2) preservation of prostatic capsule and
      enucleation of prostatic parenchyma, which is removed in block together with the
      bladder, without violating the vesical neck; 3) no manipulation of the distal
      urethral sphincteric complex; 4) preservation of seminal vesicles and maintenance
      of cavernous neurovascular bundles; 5) wide anastomosis between the ileal
      neobladder and the prostatic capsule. COMMENTS: The proposed maneuvers allow the
      performance of radical cystectomy with integral preservation of distal urethral
      sphincter and of cavernous neurovascular bundles, without jeopardizing the
      oncological principles.

PMID- 15745560
TI  - The role of videolaparoscopy in the diagnostic and therapeutic approach of
      nonpalpable testis.
AB  - OBJECTIVE: Evaluate the results from the first 5 years of experience with
      laparoscopy for diagnosis and treatment of nonpalpable testes. MATERIALS AND
      METHODS: Medical records of 51 patients submitted to laparoscopic testicular
      exploration, during a 5-year period, were retrospectively analyzed. Patients'
      mean age was 65.7 months (median = 48) on the first procedure. The youngest
      patient was 10 months and the oldest was 14 years old on the first surgery.
      Twenty-four (47%) patients presented nonpalpable testes bilaterally, 7 (14%) only
      at the right side and 20 (39%) at the left, totaling 75 testicular units
      assessed. Patients who had their testes palpated after anesthetic induction were
      excluded from the study, and in all other cases, surgical management was based on
      the testicular position and viability. During the post-operative follow-up,
      surgical success was classified as palpable testis in scrotal sac, with adequate
      consistency and volume. RESULTS: Nine (12%) testes were not localized, but their
      vessels and deferent duct were atrophic. Two (3%) testes were intra-abdominal and
      atrophic, and 2 (3%) gonads, in the same patient, had a dysmorphic aspect.
      Nineteen (25%) testicular units were located close to the internal inguinal ring
      (peeping testes) and, in 22 (29%) units, the spermatic vessels and deferent duct
      penetrated the internal inguinal ring. Eight (10%) testes were located at a
      distance of less than 2 cm from the internal inguinal ring and 13 (17%) at a
      distance greater than 2 cm. The 2 intra-abdominal atrophic testes were removed.
      Inguinotomy was performed in a total of 41 (54%) cases, reaching a surgical
      success of 89%. Laparoscopic orchiopexy in one stage, without vascular ligation,
      was performed in 9 (12%) testes, which presented a distance of less than 2 cm
      from the internal inguinal ring, also with a surgical success index of 89%.
      Orchiopexy in 2 stages, with ligation of the spermatic vessels, was performed in
      13 (17%) testicular units located at a distance greater than 2 cm from the
      internal inguinal ring, reaching 77% of good results. CONCLUSION:
      Videolaparoscopy is a safe and effective method for diagnosis and treatment of
      nonpalpable testis.

PMID- 15745561
TI  - Safyre: a readjustable minimally invasive sling for female urinary stress
      incontinence.
AB  - INTRODUCTION: SAFYRE is a readjustable and minimally invasive sling for the
      treatment of stress urinary incontinence (SUI). It is as a pubovaginal sling
      placed in the medial third of the urethra. The initial experience is described.
      MATERIALS AND METHODS: Forty-five patients (mean age = 59 years) underwent a
      SAFYRE implant to treat SUI. Physical examination and urodynamic study were
      performed before surgery. All patients presented symptoms of SUI and 20% also
      reported mild urgency. Approximately 60% of this group had a previously failed
      anti-incontinence procedure. Urethral hypermobility was diagnosed in 40% of the
      patients and intrinsic sphincter deficiency (ISD) in 60% of the cases. RESULTS:
      The average follow up period was 10 months. The mean operative time was 20
      minutes. Dystopia repair was performed whenever necessary, during the same
      procedure. The average hospital stay was 24 hours. In 11% of the implants,
      bladder perforation occurred. During the postoperative period, 9 patients (20%)
      developed transient urgency symptoms. During the initial follow up period, 90%
      were found to be continent, 3% reported an improvement and 7% were unchanged.
      CONCLUSION: SAFYRE is a safe and quick procedure that allows postoperative
      readjustment. This technique may be an attractive alternative in the management
      of SUI, should the good result obtained so far prove to be long lasting.

PMID- 15745583
TI  - Priapism - etiology, pathophysiology and management.
AB  - The understanding of erectile physiology has improved the prompt diagnosis and
      treatment of priapism. Priapism is defined as prolonged and persistent erection
      of the penis without sexual stimulation and failure to subside despite orgasm.
      Numerous etiologies of this condition are considered. Among others a disturbed
      detumescence mechanism, which may due to excess release of contractile
      neurotransmitters, obstruction of draining venules, malfunction of the intrinsic
      detumescence mechanism or prolonged relaxation of intracavernosal smooth muscle
      are postulated. Treatment of priapism varies from a conservative medical to a
      drastic surgical approach. Two main types of priapism; veno-occlusive low flow
      (ischemic) and arterial high flow (non-ischemic), must be distinguished to choose
      the correct treatment option for each type. Patient history, physical
      examination, penile hemodynamics and corporeal metabolic blood quality provides
      distinction between a static or dynamic pathology. Priapism can be treated
      effectively with intracavernous vasoconstrictive agents or surgical shunting.
      Alternative options, such as intracavernous injection of methylene blue (MB) or
      selective penile arterial embolization (SPEA), for the management of high and low
      flow priapism are described and a survey on current treatment modalities is
      given.

PMID- 15745584
TI  - Molecular aspects of prostate cancer: implications for future directions.
AB  - Many studies have been developed trying to understand the complex molecular
      mechanisms involved in oncogenesis and progression of prostate cancer (PCa).
      Current biotechnological methodologies, especially genomic studies, are adding
      important aspects to this area. The construction of extensive DNA sequence data
      and gene expression profiles have been intensively explored to search for
      candidate biomarkers to evaluate PCa. The use of DNA micro-array robotic systems
      constitutes a powerful approach to simultaneously monitor the expression of a
      great number of genes. The resulting gene expressing profiles can be used to
      specifically describe tumor staging and response to cancer therapies. Also, it is
      possible to follow PCa pathological properties and to identify genes that
      anticipate the behavior of clinical disease. The molecular pathogenesis of PCa
      involves many contributing factors, such as alterations in signal transduction
      pathways, angiogenesis, adhesion molecules expression and cell cycle control.
      Also, molecular studies are making clear that many genes, scattered through
      several different chromosomal regions probably cause predisposition to PCa. The
      discovery of new molecular markers for PCa is another relevant advance resulting
      from molecular biology studies of prostate tumors. Interesting tissue and serum
      markers have been reported, resulting in many cases in useful novelties to
      diagnostic and prognostic approaches to follow-up PCa. Finally, gene therapy
      comes as an important approach for therapeutic intervention in PCa. Clinical
      trials for PCa have been demonstrating that gene therapy is relatively safe and
      well tolerated, although some improvements are yet to be developed.

PMID- 15745585
TI  - Can selective retroperitoneal lymphadenectomy be better than unilateral
      retroperitoneal lymphadenectomy?
AB  - OBJECTIVE: To propose a new modality of retroperitoneal lymphadenectomy as a
      complementary treatment for patients with high risk, stage I nonseminomatous
      testicular tumor. MATERIALS AND METHODS: We studied 76 patients with stage I
      nonseminomatous testis tumor (T1-T4, NX, M0) treated by orchiectomy and
      retroperitoneal lymphadenectomy. Among them, 33 patients underwent unilateral
      retroperitoneal lymphadenectomy (URL) and 43 selective retroperitoneal
      lymphadenectomy (SRL). URL consisted in removing the lymph nodes located around
      the great vessel homolateral to the tumor (aorta or vena cava and iliac vessels),
      and anterior and posterior to the contralateral great vessel (aorta or vena
      cava). SRL was performed removing the lymph nodes located anterior and between
      the great vessels (aorta or vena cava) and laterally to the homolateral great
      vessel, extending the distal dissection until the level of inferior mesenteric
      artery. In these groups of patients, the incidence of disease recurrence, disease
      free survival index, and frequency of post-operative aspermia were assessed. Mean
      post-operative follow-up time was 96 months. RESULTS: In the SRL group there was
      only 5% of aspermia versus 79% in the URL group (p < 0.0001). Tumor recurrence
      was observed in only 5 of the 76 patients and was not related to the surgical
      technique. The disease-free survival rate after the mean follow-up of 96 months
      was similar in both groups, being 94% in the SRL group and 93% in the URL group.
      CONCLUSION: The selective retroperitoneal lymphadenectomy constitutes an
      effective technique with a lower morbidity than unilateral lymphadenectomy,
      representing an excellent option for the management of patients with high-risk,
      stage I nonseminomatous testis tumor.

PMID- 15745586
TI  - Urodynamic studies in the surgical treatment of benign prostatic hyperplasia.
AB  - OBJECTIVE: We compared the clinical and urodynamic outcome of men with lower
      urinary tract symptoms with and without previous urodynamic evaluation submitted
      to transurethral resection of the prostate. MATERIALS AND METHODS: A prospective
      and randomized study was performed in 315 patients who underwent transurethral
      resection of the prostate. In 151 patients (group A) with a mean age of 63 years,
      transurethral resection of the prostate was performed without a prior urodynamic
      study, and group B, 164 patients with a mean age of 61 years, underwent a
      urodynamic study prior to surgical procedure. In group B, only obstructed
      patients were selected for surgery. All patients had I-PSS higher than 15 and
      underwent at least 2 uroflowmetry and flow was lower than 10 ml/sec. At 6-month
      follow up, patients in both groups underwent the I-PSS questionnaire and pressure
      / flow study. RESULTS: The symptomatology and uroflowmetry did not display
      different behavior between the groups. The mean postoperative score for group A
      was 8.87 + 3.27 and for group B was 9.32 + 3.14 (p = 0.22). The mean
      postoperative uroflow for group A was 17.0 + 2.1 mL/s and for group B was 16.6 +
      2.2 mL/s (p = 0.15).Postoperative, in group A, 27 patients (17.8%) were
      obstructed and in group B, 16 patients (9.75%) were obstructed (p = 0.03).
      CONCLUSION: The study suggests that the previous urodynamic study is not the only
      factor related to the success of surgical outcome; and therefore, the
      symptomatology and uroflowmetry associated would be enough during the
      preoperative routine studies for BPH patients.

PMID- 15745587
TI  - Digital rectal examination (DRE) does not influence total serum levels of
      prostate specific antigen (tPSA), in individuals without prostate pathology.
AB  - OBJECTIVE: To evaluate if the digital rectal examination (DRE) performed before
      determination of total serum prostate specific antigen (tPSA) influences the
      levels of this protein. MATERIALS AND METHODS: Forty-eight men without a
      diagnosis of prostate pathology were assessed for tPSA levels, before and 30
      minutes after DRE examination. Values of tPSA in the individuals' serum were
      measured by the electrochemoluminescence (ECLIA), in Roche's Elecys 1010
      analyzer. RESULTS: DRE examination induced a modest elevation in tPSA values in
      34 of the 48 men, with a variation in mean elevation from 2.19% in the age range
      >/= 70 years to 11.96% in the age range of 60-69 years. Additionally, moderate
      decreases in values were detected in 11 individuals and 3 did not present any
      alteration following the procedure. Differences in mean values of tPSA, pre- and
      post-DRE were not statistically significant, neither in the total sample of
      individuals or in the age range groups. CONCLUSION: DRE examination does not
      significantly influence the tPSA values in individuals under study.

PMID- 15745588
TI  - Hemorrhagic shock due to spontaneous rupture of adrenal pheochromocytoma.
AB  - The spontaneous rupture of an adrenal pheochromocytoma is an extremely rare
      event; however, it is potentially fatal. We report a case of spontaneous rupture
      of pheochromocytoma followed by an extensive retroperitoneal hematoma and
      hypovolemic shock. The correct diagnostic assessment determined the adequate
      surgical approach and a favorable outcome for the patient.

PMID- 15745589
TI  - Urethral metastasis of lung carcinoma with germinative cell features.
AB  - INTRODUCTION: We present the case of a patient with urethral metastasis of a lung
      carcinoma with germinative cell features. CASE REPORT: A White, 57-year old man
      underwent urologic assessment due to gross hematuria. Patient was being treated
      with chemotherapy and radiotherapy during the past 3 months due to primary
      carcinoma of the lung with brain metastasis. Urethrocistoscopy and nuclear
      magnetic resonance imaging revealed a stenosing mass invading the bulbomembranous
      urethra. No other tumor was found. Biopsy specimens, obtained from the lung,
      brain and urethra tumors, revealed the same neoplasia, with definitive diagnosis
      being undifferentiated giant cell carcinoma of the lung with germinative
      features. Considering his clinical condition and poor prognosis, a decision was
      made to treat the patient only clinically. Clinical conditions deteriorated and
      the patient evolved to death within 3 months. COMMENTS: As far as we were able to
      access, urethral metastasis from lung carcinoma had never been described in the
      indexed literature. Due to the extremely limited experience with these tumors,
      there is not a defined treatment and the prognosis remains quite poor.

PMID- 15745590
TI  - Cystadenoma of the seminal vesicle.
AB  - Primary tumors of the seminal vesicle are extremely rare. Among them, there is a
      spectrum of tumors derived from both epithelium and stroma and so classified as
      epithelial-stromal tumors. Herein, we report a case of a cystadenoma in a 49-year
      old asymptomatic man, detected in a routine ultrasonography for liver disease
      follow-up. The digital rectal examination detected a large mass anterior to
      rectum and posterior to bladder. Computed tomography scan and magnetic resonance
      imaging showed a normal prostate and a 9.0 cm cystic tumor, replacing the left
      seminal vesicle. The gross appearance and microscopic aspect was compatible with
      cystadenoma of seminal vesicle. Patient's postoperative recovery was uneventful.
      He is currently alive, 3 years after the diagnosis, with no signs of recurrence.

PMID- 15745591
TI  - Glandectomy with preservation of corpora cavernosa in the treatment of penile
      carcinoma.
AB  - INTRODUCTION: The objective of this work is to describe a conservative surgical
      technique as an alternative to classic penile amputations, aiming the local
      control of the disease, in addition to trying to preserve the patient's sexual
      function. SURGICAL TECHNIQUE: After a circular incision of the skin around the
      penis, the subfascial plane is developed until the base of the organ. The dorsal
      neurovascular bundle and the urethra are isolated in their distal extremities.
      The neurovascular bundle is sectioned distally. A retrocoronal dissection plane
      is developed between the glans and the corpora cavernosa. When this stage is
      complete, the glans is fixed only to the urethra, which is distally sectioned as
      well. The neurovascular bundle is fixed to the dorsal albuginea. Following the
      spatulation of the urethra, a neomeatus is created using the overlay skin of the
      penis. Between January 2001 and July 2002, we employed this technique in 6
      patients who had epidermoid carcinoma of the penis, which were limited to the
      glans, superficial, well or moderately differentiated and measuring up to 3 cm.
      COMMENTS: Several conservative surgical methods for treatment of carcinoma of the
      penis aim the organ's preservation, in an attempt of improving the quality of
      life of patients, however the indexes of local recurrence and failure in disease
      control are significant. The described technique showed to be safe and effective
      for disease control, in addition to preserving sexual function in all patients
      who were treated, representing, thus, a quite appealing conservative surgical
      alternative in selected cases.

PMID- 15745592
TI  - Videoendoscopic surgery by extraperitoneal access: technical aspects and
      indication.
AB  - Laparoscopic surgery in urology is definitely incorporated to the techniques of
      minimally invasive treatment for urogenital diseases. Though the classic access
      to organs in the urinary tract is extraperitoneal, this access has not been
      prioritized when the videoendoscopic technique is used. In Brazil, few groups use
      this approach and little has been discussed about its true practical
      applicability. The authors intended to discuss the main technical aspects and
      criteria for indication, reported though the improvement achieved in a 5-year
      period with 150 operated cases. A review of the literature shows that the worldly
      acceptance of the extraperitoneal endoscopic approach is increasing.
      Nevertheless, there are no evidences that the extraperitoneal access is superior
      to the transperitoneal route. Thus, the choice depends basically on the surgeon's
      preference. Major advantages are the immediate access to the renal hilum and
      isolation of peritoneal structures. Employing this access is useful when one
      suspects that significant peritoneal adherences could prevent the surgical act or
      when one wishes to preserve the integrity of the peritoneal cavity.

PMID- 15745593
TI  - Etiology of urinary tract infection in scholar children.
AB  - OBJECTIVE: To prospectively assess the prevalence of vesicourethral dysfunction
      in children over 3 years old, comparing it with the occurrence rate for other
      potential factors that cause urinary infection in this age range. MATERIALS AND
      METHODS: 36 girls and 9 boys were assessed, with mean age of 6.4 years, ranging
      from 3 to 13.9 years. These children were prospectively assessed regarding the
      presence of symptoms of lower urinary tract dysfunction. These data were compared
      with the retrospective assessment of other potential risk factors for urinary
      infection. Ultrasonography was performed in 28 children and voiding
      cystourethrogram was performed in 26 patients. RESULTS: Vesicourethral
      dysfunction was diagnosed in 39 (87%) of the 45 children with urinary infection.
      Among these 39 patients, all had voiding urgency, 30 (77%) had urinary
      incontinence, 12 (31%) pollakiuria and 3 (8%) presented infrequent voiding.
      Vaginal discharge was evidenced in 8 (22%) girls and phimosis in 2 (22%) boys.
      Obstipation was diagnosed in 10 (22%) cases. Significant post-voiding residue was
      detected in 4 (13%) of the 28 cases assessed. Vesicoureteral reflux was evidenced
      in 5 (19%) of the 26 patients who underwent voiding cystourethrogram. In only 2
      (4%) cases there was not an apparent cause for the infection. CONCLUSION:
      Vesicourethral dysfunction is a major cause of urinary infection in children with
      ages above 3 years old. In cases where voiding dysfunction in not present, other
      predisposing factors must be assessed. However, only 4% of the patients did not
      present an apparent urologic cause for the infection.

PMID- 15745594
TI  - Development of bladder control in mentally handicapped children.
AB  - PURPOSE: To analyze the role of mental handicap as a possible source of lack of
      development of bladder control and to find out the chance of continence to advise
      future patients. MATERIALS AND METHODS: The parents and relatives of 100
      consecutive mentally handicapped patients were inquired by a personal interview.
      Questions included the age when they stopped using diapers, enuretic events,
      frequency, urgency and leakage episodes, urinary infections. Etiology of their
      mental problem was unknown in 34, perinatal anoxia in 17, Down syndrome in 15,
      phenylketonuria in 18 and others minors causes. The grade of mental deficiency
      were profound in 1, severe in 10, moderate in 39, mild in 33 and normal inferior
      value in 17. The age varied from 7 to 37 years old, with an average of 14 by the
      time of the interview, comprising 60 males and 40 females. RESULTS: All profound
      and severe patients presented leakage episodes regardless of the age. The mild
      and normal inferior value acquired progressive urinary control with aging, and
      33% still remain with urinary symptoms above 16 years old. Urinary infection was
      similar in males and females, around 29%. The most committed group presented less
      urinary infections. The etiology of the mental handicap was not correlated to the
      incidence of urinary leakage. CONCLUSIONS: The lack of bladder control was
      correlated to the grade of mental handicap. In severe and profound groups, the
      expectancy of control is disappointing. In the less compromised groups, there is
      a delay in bladder training, with achievement of control in (2/3) after 16 years
      of age. Those in the normal inferior value have a chance of postponed urinary
      control, easily misdiagnosed by normal urological interviews.

PMID- 15745615
TI  - Psychiatric comorbidity in fibromyalgia.
AB  - This review examines the current literature regarding psychiatric comorbidities
      associated with fibromyalgia. The aim of this review is to enhance understanding
      of psychiatric disorders that, alone or in combination with other physiologic
      (eg, neuroendocrine dysfunction) and psychosocial factors (eg, poor coping
      skills), may contribute to abnormal pain sensitivity and other illness behaviors
      of individuals with fibromyalgia. The review first identifies the psychiatric
      comorbidities that are associated most often with fibromyalgia and tend to
      aggregate within families of individuals with this disorder. It then examines the
      literature regarding the extent to which psychiatric illness, environmental
      stressors, or other psychosocial factors may contribute to the development of
      fibromyalgia. The review also presents recent findings concerning the extent to
      which psychosocial factors may contribute to treatment-related outcomes in pain
      and other health status variables among patients with fibromyalgia.

PMID- 15745616
TI  - Transcranial magnetic stimulation for central pain.
AB  - Transcranial magnetic stimulation recently has emerged as a therapeutic tool in
      neurology and psychiatry, with contradictory results. Central pain, a major
      chronic pain syndrome affecting millions of people worldwide, has been the focus
      of a few studies. Although transcranial magnetic stimulation has no role in the
      chronic management of such pain, it has potential as a screening procedure for
      the much more effective extradural cortical stimulation, a minimally invasive
      neurosurgical procedure that has emerged as the technique of choice in treating
      these patients.

PMID- 15745617
TI  - How does distraction work in the management of pain?
AB  - Engaging in thoughts or activities that distract attention from pain is one of
      the most commonly used and highly endorsed strategies for controlling pain. The
      process of distraction appears to involve competition for attention between a
      highly salient sensation (pain) and consciously directed focus on some other
      information processing activity. In this article, the evidence for distraction
      from pain is examined and the qualities of pain, the distractor, and some
      individual difference variables that have been shown influence the effectiveness
      of distraction are described. There has been little examination of the use of
      distraction in chronic pain, but some ancillary evidence suggests that it should
      be used with caution.

PMID- 15745618
TI  - What are the marital problems of patients with chronic pain?
AB  - Throughout the past two decades, researchers have studied the close relationships
      of patients to understand the role that these relationships play in the
      maintenance and alleviation of pain and the role that pain plays in affecting
      relationships. In this article, a brief review of the evidence is provided,
      showing a link between marital functioning and pain, and the marital problems
      reported by patients with chronic pain in our studies also are described. We
      provide information about several promising couples pain management and couples
      therapy approaches that appear to help couples manage pain together.
      Recommendations for clinical and research directions also are offered.

PMID- 15745619
TI  - The relationship between anger and pain.
AB  - Anger is defined with reference to a cognitive-motivational perspective. This
      forms the basis for identifying the variety of reasons why pain sufferers are
      angry and the many ways in which they react when angry. Statistics are provided
      for the comorbidity of anger in chronic pain and headache. Going beyond such
      statistics, five dynamic interactions between anger and pain are emphasized and
      empirical evidence is provided for each of these interactions.

PMID- 15745620
TI  - Cognitive processing in cluster headache.
AB  - Little is known about specific changes of cognitive processing in cluster
      headache. Studies on event-related potentials (ERP) suggest that stimulus
      evaluation is impaired in chronic cluster headache and in episodic cluster
      headache during the cluster period, but not in the interval between two periods.
      Patients with chronic paroxysmal hemicrania do not show this impairment. Unlike
      patients with migraine, patients with cluster headache do not present with a loss
      of cognitive habituation as measured by ERP. In neuropsychologic evaluations, a
      reversible decline of memory processing was detected during the cluster attack,
      but not between two attacks. Long-term observation revealed no progressive
      cognitive decline in cluster headache patients over the years. With regard to
      personality changes, a liability susceptibility to anxiety disorders and to
      hypochondriasis, but not to mood changes, has been described inconsistently. All
      changes in alterations of cognitive processing in cluster headache are
      demonstrated to be mild and do not relevantly contribute to the clinical picture
      of this disease.

PMID- 15745622
TI  - Cluster headache from the patient's point of view.
AB  - The medical literature provides few opportunities for physicians to read and
      reflect on detailed, first-hand narratives of individual patient experiences. The
      author invited patients with cluster headache to respond in writing to a series
      of open-ended questions about their experience with the illness. The patient
      responses provide important information for physicians and others who seek a more
      complete understanding of cluster headache.

PMID- 15745621
TI  - Behavior during cluster headache.
AB  - Cluster headache (CH), also known as "suicide headache," is characterized by a
      distinctive behavior during attacks. In 80% to 90% of cases, patients are
      restless and constantly moving in a vain attempt to relieve pain. They often
      perform complex, stereotyped actions. During attacks, CH sufferers do not want to
      be touched, stroked, or comforted and frequently moan a great deal, cry, or even
      scream. They sometimes indulge in violent, self-hurting behavior. Restlessness is
      a highly sensitive and highly specific parameter for CH and has been included
      among the signs and symptoms accompanying pain of the disorder in the Second
      Edition of the International Classification of Headache Disorders. A few
      hypotheses on pathophysiology of restlessness are addressed in this paper.

PMID- 15745623
TI  - Corticosteroid treatment in cluster headache: evidence, rationale, and practice.
AB  - The use of corticosteroids in the treatment of cluster headache (CH) is
      commonplace and has been a mainstay of clinical practice for this indication for
      50 years. The published evidence supporting this practice is weak, with no
      methodologically rigorous or large-scale controlled trials executed. Nonetheless,
      the clinical experiences of practitioners and the conclusion of investigators
      provide a clear signal of benefit from corticosteroid use in CH. The
      pathophysiologic explanation for this beneficial effect is unknown, but
      corticosteroid influences on inflammatory, hypothalamic-pituitary-adrenal,
      histaminergic, and opioid systems have been proposed. Best-practice parameters
      are unclear, but the professional consensus is that corticosteroids generally are
      effective for arresting CH attacks, only if administered in relatively high
      doses, and that safety concerns warrant courses of 4 weeks or less. Concomitant
      use of other prophylactic agents for CH in addition to corticosteroids usually is
      advisable because attacks often recur when the corticosteroid dose is tapered.

PMID- 15745624
TI  - History of cluster headache.
AB  - Possibly because of the manifestation of severe debilitating pain, cluster
      headache has been identified in early publications, described in exquisite detail
      by authors dating as far back as 1641. These early descriptions focused on the
      symptoms of the episodes rather than the periodicity of their occurrence. Similar
      to most medical conditions described without anatomic or clearly defined
      pathophysiologic basis, cluster headache often was named for its clinical
      manifestations, or less helpfully, by the names of the authors of its descriptive
      publications. It was only in 1952 that the condition was named for its peculiar
      tendency to occur in clusters over a period of weeks rather than being a chronic,
      recurrent, episodic condition similar to migraine. Despite having such an
      interesting mix of autonomic and physical features, this observation seems to be
      most instrumental in divulging the true pathogenesis of this disease and
      correctly localizing its origin anatomically in the hypothalamus.

PMID- 15745625
TI  - Cluster headache: diagnosis and treatment.
AB  - Cluster headache is a primary headache syndrome that is underdiagnosed and in
      many instances undertreated. The pain produced during a cluster headache is more
      severe than that generated by any other primary headache. Cluster headache is
      very stereotyped in its presentation and fairly easy to diagnose with an in depth
      headache history. Cluster headache is easy to treat in most individuals if the
      correct medications are used and the correct dosages are given. The following
      manuscript presents information on the clinical presentation of cluster headache
      and both medicinal and surgical interventions.

PMID- 15745626
TI  - Functional neuroimaging of primary headache disorders.
AB  - Until recently, primary headache disorders such as migraine and cluster headache
      were considered to be vascular in origin. However, advances in neuroimaging
      techniques, such as positron emission tomography, single photon emission
      computerized tomography, and functional magnetic resonance imaging, have
      augmented the growing clinical evidence that these headaches are primarily driven
      from the brain. This review covers functional imaging studies in migraine,
      cluster headache, rarer headache syndromes, and experimental head pain. Together
      with newer techniques, such as voxel-based morphometry and magnetic resonance
      spectrometry, functional imaging continues to play a role in elucidating and
      targeting the neural substrates in each of the primary headache syndromes.

PMID- 15745627
TI  - Meiosis and embryo technology: renaissance of the nucleolus.
AB  - The nucleolus is the site of rRNA and ribosome production. This organelle
      presents an active fibrillogranular ultrastructure in the oocyte during the
      growth of the gamete but, at the end of the growth phase, the nucleolus is
      transformed into an inactive remnant that is dissolved when meiosis is resumed at
      germinal vesicle breakdown. Upon meiosis, structures resembling the nucleolar
      remnant, now referred to as nucleolus precursor bodies (NPBs), are established in
      the pronuclei. These entities harbour the development of fibrillogranular
      nucleoli and re-establishment of nucleolar function in conjunction with the major
      activation of the embryonic genome. This so-called nucleologenesis occurs at a
      species-specific time of development and can be classified into two different
      models: one where nucleolus development occurs inside the NPBs (e.g. cattle) and
      one where the nucleolus is formed on the surface of the NPBs (e.g. pigs). A panel
      of nucleolar proteins with functions during rDNA transcription (topoisomerase I,
      RNA polymerase I and upstream binding factor) and early (fibrillarin) or late
      rRNA processing (nucleolin and nucleophosmin) are localised to specific
      compartments of the oocyte nucleolus and those engaged in late processing are, to
      some degree, re-used for nucleologenesis in the embryo, whereas the others
      require de novo embryonic transcription in order to be allocated to the
      developing nucleolus. In the oocyte, inactivation of the nucleolus coincides with
      the acquisition of full meiotic competence, a parameter that may be of importance
      in relation to in vitro oocyte maturation. In embryo, nucleologenesis may be
      affected by technological manipulations: in vitro embryo production apparently
      has no impact on this process in cattle, whereas in the pig this technology
      results in impaired nucleologenesis. In cattle, reconstruction of embryos by
      nuclear transfer results in profound disturbances in nucleologenesis. In
      conclusion, the nucleolus is an organelle of great importance for the
      developmental competence of oocytes and embryos and may serve as a morphological
      marker for the completion of oocyte growth and normality of activation of the
      embryonic genome.

PMID- 15745628
TI  - Role of the mitochondrial genome in preimplantation development and assisted
      reproductive technologies.
AB  - Our fascination for mitochondria relates to their origin as symbiotic, semi
      independent organisms on which we, as eukaryotic beings, rely nearly exclusively
      to produce energy for every cell function. Therefore, it is not surprising that
      these organelles play an essential role in many events during early development
      and in artificial reproductive technologies (ARTs) applied to humans and domestic
      animals. However, much needs to be learned about the interactions between the
      nucleus and the mitochondrial genome (mtDNA), particularly with respect to the
      control of transcription, replication and segregation during preimplantation.
      Nuclear-encoded factors that control transcription and replication are expressed
      during preimplantation development in mice and are followed by mtDNA
      transcription, but these result in no change in mtDNA copy number. However, in
      cattle, mtDNA copy number increases during blastocyst expansion and hatching.
      Nuclear genes influence the mtDNA segregation patterns in heteroplasmic animals.
      Because many ARTs markedly modify the mtDNA content in embryos, it is essential
      that their application is preceded by careful experimental scrutiny, using
      suitable animal models.

PMID- 15745629
TI  - Messenger RNA expression patterns in bovine embryos derived from in vitro
      procedures and their implications for development.
AB  - The preimplantation bovine embryo is initially under the control of maternal
      genomic information that is accumulated during oogenesis. The genetic programme
      of development soon becomes dependent on new transcripts derived from activation
      of the embryonic genome. The early steps in development, including the timing of
      the first cleavage, activation of the embryonic genome, compaction and blastocyst
      formation, can be affected by the culture media and conditions, as well as the
      production procedure itself. These perturbations can possibly result in a marked
      decrease in the quality of the resulting blastocysts and may even affect the
      viability of offspring born after transfer. In vitro procedures such as in vitro
      production and somatic nuclear transfer of bovine embryos have been shown to be
      correlated with significant up- or downregulation, de novo induction or silencing
      of genes critical for undisturbed fetal and neonatal development. These
      alterations are likely to be caused by epigenetic modifications, such as DNA
      methylation and histone modifications. Analysis of perturbed epigenetic
      reprogramming and of the related phenomena, such as genomic imprinting and X
      chromosome inactivation, in bovine embryos is promising for understanding the
      underlying mechanisms of developmental abnormalities, such as large offspring
      syndrome.

PMID- 15745630
TI  - Whole-genome approaches for large-scale gene identification and expression
      analysis in mammalian preimplantation embryos.
AB  - The elucidation, unravelling and understanding of the molecular basis of
      transcriptional control during preimplantation development is of utmost
      importance if we are to intervene and eliminate or reduce abnormalities
      associated with growth, disease and infertility by applying assisted
      reproduction. Importantly, these studies should enhance our knowledge of basic
      reproductive biology and its application to regenerative medicine and livestock
      production. A major obstacle impeding progress in these areas is the ability to
      successfully generate molecular portraits of preimplantation embryos from their
      minute amounts of RNA. The present review describes the various approaches
      whereby classical embryology fuses with molecular biology, high-throughput
      genomics and systems biology to address and solve questions related to early
      development in mammals.

PMID- 15745631
TI  - Potential and limitations of bovine-specific arrays for the analysis of mRNA
      levels in early development: preliminary analysis using a bovine embryonic array.
AB  - New insights into the early development of large mammals are becoming available
      through the measurement of differential mRNA levels in oocytes and
      preimplantation embryos. These advances in knowledge are rapidly picking up in
      pace, mainly owing to the advantages brought by new molecular biology approaches
      being developed. The possibility of amplifying the starting material and
      therefore making measurements in single embryo units is now feasible. With these
      tools, the evaluation of variations in gene expression patterns during the
      preimplantation period or the impact of culture on mRNA levels is now possible.
      However, it is important to keep in mind that these methods still have
      limitations associated with sample preparation or the use of the appropriate
      controls. Even proper methods of analysis are very important to achieve the full
      benefit of the application of these tools. The present paper describes some of
      the potential, as well as limitations, of mRNA level analysis in early embryos,
      especially for microarray analysis. We have generated a bovine cDNA array (>2000
      clones) that contains expressed sequence tags (ESTs) collected from various
      preimplantation development stages. Using this chip, we have initiated the
      characterisation of global mRNA level patterns of several key developmental
      stages from the immature oocyte to the blastocyst stage. As expected, the
      hybridisation results indicate very different expression profiles involving
      hundreds of genes when comparing oocyte and blastocyst samples to a reference
      mRNA sample made from a pool of ESTs from pooled somatic tissues. Although this
      array is still in its preliminary stage and the EST bank has not been processed
      to contain only unigenes, it is already a very useful tool for discovering
      candidate genes that may play important roles during early embryonic life.

PMID- 15745632
TI  - Commercial applications of nuclear transfer cloning: three examples.
AB  - Potential applications of cloning go well beyond the popularly envisioned
      replication of valuable animals. This is because targeted genetic modifications
      can be made in donor cells before nuclear transfer. Applications that are
      currently being pursued include therapeutic protein production in the milk and
      blood of transgenic cloned animals, the use of cells, tissues and organs from
      gene-modified animals for transplantation into humans and genetically modified
      livestock that produce healthier and safer products in an environmentally
      friendly manner. Commercial and social acceptance of one or more of these early
      cloning applications will lead to yet unimagined applications of nuclear transfer
      technology. The present paper summarises progress on three additional
      applications of nuclear transfer, namely the development of male livestock that
      produce single-sex sperm, the transfer of immune responses from animals to their
      clones to permit the production of unlimited supplies of unique polyclonal
      antibodies, and the generation of genetically modified animals that accurately
      mimic human diseases for the purpose of developing new therapies. However, the
      myriad applications of cloning will require appropriate safeguards to ensure
      safe, humane and responsible outcomes of the technology.

PMID- 15745633
TI  - Mitochondria and the success of somatic cell nuclear transfer cloning: from
      nuclear-mitochondrial interactions to mitochondrial complementation and
      mitochondrial DNA recombination.
AB  - The overall success of somatic cell nuclear transfer (SCNT) cloning is rather
      unsatisfactory, both in terms of efficacy and from an animal health and welfare
      point of view. Most research activities have concentrated on epigenetic
      reprogramming problems as one major cause of SCNT failure. The present review
      addresses the limited success of mammalian SCNT from yet another viewpoint, the
      mitochondrial perspective. Mitochondria have a broad range of critical functions
      in cellular energy supply, cell signalling and programmed cell death and, thus,
      affect embryonic and fetal development, suggesting that inadequate or perturbed
      mitochondrial functions may adversely affect SCNT success. A survey of perinatal
      clinical data from human subjects with deficient mitochondrial respiratory chain
      activity has revealed a plethora of phenotypes that have striking similarities
      with abnormalities commonly encountered in SCNT fetuses and offspring. We discuss
      the limited experimental data on nuclear-mitochondrial interaction effects in
      SCNT and explore the potential effects in the context of new findings about the
      biology of mitochondria. These include mitochondrial fusion/fission,
      mitochondrial complementation and mitochondrial DNA recombination, processes that
      are likely to be affected by and impact on SCNT cloning. Furthermore, we indicate
      pathways that could link epigenetic reprogramming and mitochondria effects in
      SCNT and address questions and perspectives for future research.

PMID- 15745634
TI  - Telomere length regulation during cloning, embryogenesis and ageing.
AB  - Telomeres are nucleoprotein complexes at the end of eukaryotic chromosomes with
      an essential role in chromosome capping. Owing to the end-replication problem of
      DNA polymerase, telomeres shorten during each cell division. When telomeres
      become critically short, they loose their capping function, which in turn induces
      a DNA damage-like response. This mechanism inhibits cell proliferation at the
      senescence stage and there is evidence that it limits the regenerative capacity
      of tissues and organs during chronic diseases and ageing. The holoenzyme
      telomerase synthesises telomeric DNA de novo, but, in humans, it is active only
      during embryogenesis, in immature germ cells and in a subset of stem/progenitor
      cells during postnatal life. Telomere length can be maintained or increased by
      telomerase, a process that appears to be regulated by a variety of telomere
      binding proteins that control telomerase recruitment and activity at the
      telomeres. During embryogenesis, telomerase is strongly activated at the
      morula/blastocyst transition. At this transition, telomeres are significantly
      elongated in murine and bovine embryos. Early embryonic telomere elongation is
      telomerase dependent and leads to a rejuvenation of telomeres in cloned bovine
      embryos. Understanding of the molecular mechanisms underlying this early
      embryonic telomere elongation programme is of great interest for medical research
      in the fields of regeneration, cell therapies and therapeutic cloning.

PMID- 15745635
TI  - Hand-made cloning approach: potentials and limitations.
AB  - Two major drawbacks hamper the advancement of somatic cell nuclear transfer in
      domestic animals. The first is a biological problem that has been studied
      extensively by many scientists and from many viewpoints, including the cell,
      molecular and developmental biology, morphology, biochemistry and tissue culture.
      The second is a technical problem that may be responsible for 50% or more of
      quantitative and/or qualitative failures of routine cloning experiments and is
      partially the result of the demanding and complicated procedure. However, even
      the relatively rare documented efforts focusing on technique are usually
      restricted to details and accept the principles of the micromanipulator-based
      approach, with its inherent limitations. Over the past decade, a small
      alternative group of procedures, called hand-made cloning (HMC), has emerged that
      has the common feature of removal of the zona pellucida prior to enucleation and
      fusion, resulting in a limited (or no) requirement for micromanipulators. The
      benefits of HMC are low equipment costs, a simple and rapid procedure and an in
      vitro efficiency comparable with or higher than that of traditional nuclear
      transfer. Embryos created by the zona-free techniques can be cryopreserved and,
      although data are still sparse, are capable of establishing pregnancies and
      resulting in the birth of calves. Hand-made cloning may also open the way to
      partial or full automation of somatic cell nuclear transfer. Consequently, the
      zona- and micromanipulator-free approach may become a useful alternative to
      traditional cloning, either in special situations or generally for the
      standardisation and widespread application of somatic cell nuclear transfer.

PMID- 15745636
TI  - Attempts towards derivation and establishment of bovine embryonic stem cell-like
      cultures.
AB  - Current knowledge on the biology of mammalian embryonic stem cells (ESC) is
      stunningly sparse in light of their potential value in studies of development,
      functional genomics, generation of transgenic animals and human medicine. Despite
      many efforts to derive ESC from other mammalian species, ESC that retain their
      capacity for germ line transmission have only been verified in the mouse.
      However, the criterion of germ line transmission may not need to be fulfilled for
      exploitation of other abilities of these cells. Promising results with human ESC
      like cells and adult stem cells have nourished great expectations for their
      potential use in regenerative medicine. However, such an application is far from
      reality and substantial research is required to elucidate aspects of the basic
      biology of pluripotent cells, as well as safety issues associated with the use of
      such cells in therapy. In this context, methods for the derivation, propagation
      and differentiation of ESC-like cultures from domestic animals would be highly
      desirable as biologically relevant models. Here, we review previously published
      efforts to establish bovine ESC-like cells and describe a procedure used in
      attempts to derive similar cells from bovine Day 12 embryos.

PMID- 15745637
TI  - From fibroblasts and stem cells: implications for cell therapies and somatic
      cloning.
AB  - Pluripotent embryonic stem cells (ESCs) from the inner cell mass of early murine
      and human embryos exhibit extensive self-renewal in culture and maintain their
      ability to differentiate into all cell lineages. These features make ESCs a
      suitable candidate for cell-replacement therapy. However, the use of early
      embryos has provoked considerable public debate based on ethical considerations.
      From this standpoint, stem cells derived from adult tissues are a more easily
      accepted alternative. Recent results suggest that adult stem cells have a broader
      range of potency than imagined initially. Although some claims have been called
      into question by the discovery that fusion between the stem cells and
      differentiated cells can occur spontaneously, in other cases somatic stem cells
      have been induced to commit to various lineages by the extra- or intracellular
      environment. Recent data from our laboratory suggest that changes in culture
      conditions can expand a subpopulation of cells with a pluripotent phenotype from
      primary fibroblast cultures. The present paper critically reviews recent data on
      the potency of somatic stem cells, methods to modify the potency of somatic cells
      and implications for cell-based therapies.

PMID- 15745638
TI  - Derivation characteristics and perspectives for mammalian pluripotential stem
      cells.
AB  - Pluripotential stem cells have been derived in mice and primates from
      preimplantation embryos, postimplantation embryos and bone marrow stroma.
      Embryonic stem cells established from the inner cell mass of the mouse and human
      blastocyst can be maintained in an undifferentiated state for a long time by
      continuous passage on embryonic fibroblasts or in the presence of specific
      inhibitors of differentiation. Pluripotential stem cells can be induced to
      differentiate into all the tissues of the body and are able to colonise tissues
      of interest after transplantation. In mouse models of disease, there are numerous
      examples of improved tissue function and correction of pathological phenotype.
      Embryonic stem cells can be derived by nuclear transfer to establish genome
      specific cell lines and, in mice, it has been shown that embryonic stem cells are
      more successfully reprogrammed for development by nuclear transfer than somatic
      cells. Pluripotential stem cells are a very valuable research resource for the
      analysis of differentiation pathways, functional genomics, tissue engineering and
      drug screening. Clinical applications may include both cell therapy and gene
      therapy for a wide range of tissue injury and degeneration. There is considerable
      interest in the development of pluripotential stem cell lines in many mammalian
      species for similar research interests and applications.

PMID- 15745639
TI  - Comparison of neurosphere cells with cumulus cells after fusion with embryonic
      stem cells: reprogramming potential.
AB  - Embryonic stem cells (ESCs) are the pluripotent cells that also have the capacity
      to induce the genomic reprogramming of differentiated somatic cells. The
      progressively restricted genomic potential of somatic cells observed during
      embryonic development can be reverted to a pluripotent state by the formation of
      cell hybrids with ESCs. To assess the reprogramming potential of ESCs, we
      investigated the reprogramming of one of two different somatic cell populations,
      neurosphere cells (NSCs) and cumulus cells (CCs), after fusion with ESCs.
      Specifically, hybrid cells were produced by cell fusion of E14 ESCs with either
      NSCs or CCs containing the neo/lacZ and Oct4-GFP transgenes. The first
      reprogramming event, observed by the presence of Oct4-GFP in the hybrid cells,
      could be identified on Day 2, at approximately 45 h after fusion in both ESC-NSC
      and ESC-CC hybrids. In addition, the two ESC-somatic cell hybrids exhibit a
      similar reprogramming rate and share characteristics with the E14 ESC line: (1)
      expression of pluripotent markers (Oct4, Rex-1 and nanog); (2) inactivation of
      differentiated tissue-specific gene expression; and (3) the capacity to
      differentiate into all three germ layers. Taken together, our results suggest
      that the ESC-somatic cell hybrids have fully acquired ESC characteristics and
      that somatic cells of different tissue origin have the same potential to be
      reprogrammed after fusion with ESCs.

PMID- 15745640
TI  - Assisted reproductive technologies and birth outcomes: overview of recent
      systematic reviews.
AB  - Several systematic reviews have been published recently on birth outcomes of
      infants conceived through assisted reproductive technologies (ART), compared with
      infants conceived spontaneously. These outcomes include perinatal mortality,
      preterm birth, low birthweight and birth defects. Methodological limitations of
      many of the individual studies (including small sample size, potential for bias
      in ascertainment of outcomes and considering singletons and multiples together)
      were obviated in these reviews by excluding studies where methods were considered
      inadequate, by conducting meta-analyses using data from all methodologically
      sound studies (small and large) and by examining singletons separately. Overall,
      the reviews indicate few differences between outcomes in ART twins compared with
      twins conceived spontaneously. However, in singleton ART infants, there are
      around two-fold increases in risk of perinatal mortality, low birthweight and
      preterm birth, about a 50% increase in small for gestational age and a 30-35%
      increase in birth defects, compared with singletons conceived spontaneously.
      Couples considering ART should be counselled about the increased risk of adverse
      outcomes. Epidemiologists, in conjunction with clinical and laboratory
      colleagues, should now focus on large, methodologically sound studies with long
      term follow up that seek to identify the reasons for these increased risks and
      their long-term consequences, whether they are associated with particular
      technologies and causes of infertility, and how they might be reduced.

PMID- 15745641
TI  - The role of early embryonic environment on epigenotype and phenotype.
AB  - The influence of epigenetic modifications to the genome on the phenotype of the
      adult organism is now a tractable problem in biology. This has come about through
      the development of methods that enable us to study the methylation state of the
      DNA and the packaging of the chromatin at specific gene loci. It is becoming
      clear that early embryogenesis is a critical period for the establishment of the
      epigenotype. Furthermore, it appears that this process is sensitive to
      environmental conditions. This is a concern in light of the increasing use of
      artificial reproductive technologies throughout the world.

PMID- 15745642
TI  - Diet during pregnancy, neonatal outcomes and later health.
AB  - Renewed interest in nutrition during pregnancy has been generated by the
      hypothesis that adult disease has origins in early life. Animal experiments
      clearly show that altering maternal diet before and during pregnancy can induce
      permanent changes in the offspring's birth size, adult health and lifespan. Among
      women living in Western societies, cigarette smoking is the most important factor
      known to reduce fetal growth, followed by low pre-pregnancy weight and low
      gestational weight gain. Obesity is also associated with pregnancy complications
      and adverse neonatal outcomes, so inadequate or excessive energy intake is not
      optimal for the developing fetus. Against a history of inconsistent results,
      several recent studies suggest that in Western settings the balance of
      macronutrients in a woman's diet can influence newborn size. Effects appear to be
      modest, but this relationship may not encapsulate the full significance for
      health of the child, as there is emerging evidence of associations with long-term
      metabolic functioning that are independent of birth size. Consequences of
      inadequate maternal nutrition, for the offspring, may depend on timing during
      gestation, reflecting critical windows for fetal development. Where women are not
      malnourished, changing a woman's nutritional plane during pregnancy may be
      detrimental to the unborn baby, and systematic reviews of the literature on
      dietary supplementation during pregnancy indicate few benefits and possible
      risks. In view of this, improved diet before pregnancy deserves greater
      attention.

PMID- 15745643
TI  - Early origins of polycystic ovary syndrome.
AB  - The prenatally androgenised female rhesus monkey has become a model for
      polycystic ovary syndrome (PCOS) in women, with early prenatal androgenisation
      entraining a permanent PCOS-like phenotype characterised by luteinising hormone
      (LH) hypersecretion due to reduced hypothalamic sensitivity to steroid negative
      feedback and relative insulin excess associated with increased abdominal
      adiposity. These combined reproductive and metabolic abnormalities occur in
      combination with ovarian hyperandrogenism and follicular arrest in adulthood, and
      with premature follicle differentiation and impaired embryo development during
      gonadotrophin therapy for in vitro fertilization (IVF). The ability of prenatal
      androgen excess in fetal rhesus monkeys to entrain multiple organ systems in
      utero provides evidence that the hormonal environment of intrauterine life
      programmes target tissue differentiation, raising the possibility that
      hyperandrogenism in human fetal development promotes PCOS in adulthood. This
      hypothesis developed in prenatally androgenised female rhesus monkeys, however,
      also must include data from clinical studies of PCOS to clarify the homology
      between human and non-human primates in intrafollicular steroidogenesis and its
      impact on oocyte developmental competency. By doing so, future studies promise to
      develop new clinical strategies that will lead to improved pregnancy outcome and
      reduced pregnancy loss in women with disorders of insulin action, including PCOS,
      obesity and diabetes mellitus.

PMID- 15745644
TI  - Ex vivo early embryo development and effects on gene expression and imprinting.
AB  - The environment to which the mammalian embryo is exposed during the
      preimplantation period of development has a profound effect on the physiology and
      viability of the conceptus. It has been demonstrated that conditions that alter
      gene expression, and in some instances the imprinting status of specific genes,
      have all previously been shown to adversely affect cell physiology. Thus,
      questions are raised regarding the aetiology of abnormal gene expression and
      altered imprinting patterns, and whether problems can be averted by using more
      physiological culture conditions. It is also of note that the sensitivity of the
      embryo to its surroundings decreases as development proceeds. Post compaction,
      environmental conditions have a lesser effect on gene function. This, therefore,
      has implications regarding the conditions used for IVF and the culture of the
      cleavage stage embryo. The developmental competence of the oocyte also impacts
      gene expression in the embryo, and therefore superovulation has been implicated
      in abnormal methylation and imprinting in the resultant embryo. Furthermore, the
      genetics and dietary status of the mother have a profound impact on embryo
      development and gene expression. The significance of specific animal models for
      human assisted reproductive technologies (ART) is questioned, given that most
      cattle data have been obtained from in vitro-matured oocytes and that genes
      imprinted in domestic and laboratory animals are not necessarily imprinted in the
      human. Patients treated with ART have fertility problems, which in turn may
      predispose their gametes or embryos to greater sensitivities to the process of
      ART. Whether this is from the drugs involved in the ovulation induction or from
      the IVF, intracytoplasmic sperm injection or culture procedures themselves
      remains to be determined. Alternatively, it may be that epigenetic alterations
      are associated with infertility and symptoms are subsequently revealed through
      ART. Whatever the aetiology, continued long-term monitoring of the children
      conceived through ART is warranted.

PMID- 15745645
TI  - Understanding cellular disruptions during early embryo development that perturb
      viability and fetal development.
AB  - An inability to regulate ionic and metabolic homeostasis is related to a
      reduction in the developmental capacity of the embryo. The early embryo soon
      after fertilisation and up until compaction appears to have a reduced capacity to
      regulate its homeostasis. The reduced ability to regulate homeostasis, such as
      intracellular pH and calcium levels, by the precompaction-stage embryo appears to
      impact on the ability to regulate mitochondrial function and maintain adequate
      levels of energy production. This reduction in ATP production causes a cascade of
      events leading to disrupted cellular function and, perhaps ultimately, disrupted
      epigenetic regulation and aberrant placental and fetal development. In contrast,
      after compaction the embryo takes on a more somatic cell-like physiology and is
      better able to regulate its physiology and therefore appears less vulnerable to
      stress. Therefore, for human IVF it would seem important for the establishment of
      healthy pregnancies that the embryos are maintained in systems that are designed
      to minimise homeostatic stress, particularly for the cleavage-stage embryos, as
      exposure to stress is likely to culminate in impaired embryo function.

PMID- 15745646
TI  - Fetal programming: the perspective of single and twin pregnancies.
AB  - Multiple pregnancy is associated with increased risk of adverse consequences for
      both mother and fetus(es), including increased rates of maternal hypertension and
      pre-eclampsia, spontaneous abortion, Caesarean delivery, low birthweight, birth
      prematurity, perinatal mortality, admission to neonatal intensive care and
      extended length of care, respiratory distress, cerebral palsy, developmental
      delay, contact with disability services and mortality to age 5 years. Premature
      birth, which affects 97% of triplets and 53.3% of twins in Australia, is not the
      sole factor involved. The rate of multiple pregnancy in Australia is 1.7%. This
      compares to 22.1% for pregnancies resulting from assisted reproduction technology
      (ART). As a result, 21.8% of babies born from ART are from a multiple pregnancy,
      in comparison to the USA where the majority of babies born from ART are from a
      multiple pregnancy. Additionally, the population rate of multiple births is
      rising due to the more frequent use of ART and continued multi-embryo transfers,
      which is operating against a background of rising implantation rates within ART
      clinics. Twins have been of interest from a programming perspective. However,
      analysis of associations between crude birthweight and subsequent metabolic risk
      factors or mortality in adulthood from chronic disease indicate that adaptations
      in pregnancy to support multi-fetal growth are not identical to fetal growth
      restriction in singleton pregnancies. Indeed, the process of 'maternal
      constraint' is incompletely understood and confounds such comparisons. From a
      programming perspective, it is a challenge to identify in twin pregnancies the
      transition from physiological adaptation to pathological growth restriction.
      Growth disparity between twins has been more illuminating of subtle adverse
      effects for the smaller of twin pairs in both blood pressure and insulin
      resistance in adulthood. Interestingly, these effects can be observed in both
      dizygotic and to a lesser degree in monozygotic twins, which indicates a role for
      both genetic and environmental factors in these measures. This suggests that,
      consistent with experimental studies in other species, the relationship between
      impaired growth in utero and chronic disease in later life is not simply mediated
      by a common genetic pathway.

PMID- 15745647
TI  - Rewards and risks of human embryo creation: a personal view.
AB  - Understanding how a single cell, the fertilised egg, can develop into all the
      tissues in the body has been referred to as one of the two great problems facing
      biology; the other is how the brain works. To be working on the early human
      embryo is a reward in itself. To see such knowledge applied to improve the lives
      of infertile couples provides special rewards. There are considerable technical
      challenges in these activities due to the paucity of experimental material,
      particularly in the human. A major intellectual challenge is to understand the
      mechanisms that regulate early embryo development, especially the role of signal
      molecules intrinsic to the embryo and those that are maternally derived. Central
      to this issue are notions of embryo autonomy and plasticity; the extent to which
      the same genotype can give rise to different phenotypes in response to
      environmental perturbations and the need to discover how severe such changes have
      to be to induce irreversible changes that can compromise the health of the
      offspring. Research areas that could be fruitful include stress-induced causal
      effects, cell signalling and the concept of 'quiet metabolism'. Managing assisted
      conception practices and their associated risks requires a regulatory framework
      to ensure the safety and efficacy of the new technologies. However, there is a
      danger of over-regulation, a cultural phenomenon characterised by a rise in audit
      and decline in trust. The challenge is to devise regulation in assisted
      reproduction technologies proportionate to the risks. The ultimate rewards will
      come from understanding how the human genome operates in functional terms. The
      ideal system in which to study this is the human blastocyst, an autonomous,
      functional group of mammalian cells.

PMID- 15745650
TI  - Validation of a tool to measure processes of change for fruit and vegetable
      consumption among male college students.
AB  - OBJECTIVE: To develop a valid tool to measure processes of change for fruit and
      vegetable consumption, and examine the relationship between stage and processes
      of change among several cultural groups. DESIGN: Cross-sectional, using a self
      report questionnaire. SETTING: Convenience sample of male college students living
      in apartments. PARTICIPANTS: 105 US white, 53 international Latino, and 92
      international Asian males. MAIN OUTCOME MEASURES: Fruit and vegetable intake,
      stage and processes of change characterizations. ANALYSIS: Analysis of
      covariance, with age as a covariate, was used to determine differences in
      processes of change scores among 3 cultural groups and stages of change. Two-way
      analysis of variance investigated relationships between stage of change and fruit
      and vegetable consumption. The pattern of differences across cultural groups was
      examined using chi-squared analysis. RESULTS: Self-reported fruit and vegetable
      intake was higher (P < .01) in action and maintenance than in other stages.
      Participants in precontemplation/contemplation used significantly less of any
      process of change than those in preparation or action/maintenance. There were no
      significant interactions between stage of change and culture for any of the
      processes of change, but international Asians used significantly more dramatic
      relief and environmental reevaluation than did US whites and more stimulus
      control processes than US whites or international Latinos. At all stages,
      students used significantly more cognitive/experiential processes than behavioral
      processes. CONCLUSIONS AND IMPLICATIONS: The use of processes increased within
      action-oriented stages, consistent with previous studies using the
      Transtheoretical Model in the nutritional area. The greater use of
      cognitive/experiential than behavioral processes at all stages was not consistent
      with predictions. Evidence of cultural differences in the use of processes of
      change was found.

PMID- 15745652
TI  - Overview of computerized dietary assessment programs for research and practice in
      nutrition education.
AB  - Computerized dietary assessment programs are often used for nutrition education
      research and practice. This article provides an informal overview of 29 dietary
      assessment programs mentioned in the literature covered by MEDLINE from 1996 to
      2003, along with the components and capabilities of these programs derived from
      additional sources as needed. According to the literature, the advantages of
      using computers for dietary assessment include standardization of the questioning
      sequence, fast and easy processing, immediate results, and increased flexibility.
      The disadvantages include the need for typing skills and computer literacy, as
      well as potential bias in the responses if an interviewer is required.

PMID- 15745651
TI  - Impact of diet-related cancer prevention messages written with cognitive and
      affective arguments on message characteristics, stage of change, and self
      efficacy.
AB  - OBJECTIVE: To determine if participants reading messages matched to a preferred
      style of message argument respond more favorably than participants reading
      unmatched messages. DESIGN: Randomized trial using telephone and in-person
      surveys and cognitive response interviews. SETTING: University campus.
      PARTICIPANTS: Of 125 initially interested, a convenience sample of 100 university
      employees completed the study (female: 88%, white: 94%, mean age: 43.7).
      INTERVENTION(S): Participants read 2 print messages written with cognitive (COG)
      (fact based) or affective (AFF) (story based) arguments. MAIN OUTCOME MEASURE(S):
      7-point Likert scale ratings of message appeal, understandability,
      persuasiveness, and relevance according to classification into 1 of 4 message
      groups: COG-AFF (mismatched to affective), AFF-COG (mismatched to cognitive), COG
      COG (matched cognitive), and AFF-AFF (matched affective). ANALYSIS: 1-way
      analysis of variance (P < or = .05) and systematic review of qualitative
      interviews. RESULTS: The COG-AFF group consistently gave the lowest ratings to
      the affective messages and the AFF-COG group generally gave high scores compared
      with other message groups. Participants also expressed a desire for more factual
      information. CONCLUSIONS AND IMPLICATIONS: A combination of cognitive and
      affective arguments may be appealing to subjects with an affective preference but
      disliked by individuals who prefer only a fact-based approach. Argument format
      may be an important message design consideration.

PMID- 15745653
TI  - Portrayals of food practices and exercise behavior in popular American films.
AB  - OBJECTIVE: To describe depictions of food, alcohol, and exercise and sport in
      popular films. DESIGN: Content analysis of the 10 top-grossing films each year
      from 1991 to 2000 (N = 100 films). ANALYSIS: Coding reliabilities were assessed
      with Cohen's kappa. Research questions were addressed with basic descriptive
      statistics. Associations among variables were examined through a cross-tabulation
      procedure that corrects for the clustering of exercise and food depictions within
      movies. RESULTS: Food and drink appeared regularly in the films analyzed,
      typically as a background element or prop. On average, food appeared on the
      screen once every 4.2 minutes. The foods shown were most likely to be fats, oils,
      and sweets; fruits, vegetables, and dairy products were rarely seen. More than
      20% of the food items shown were alcoholic beverages, which were nearly 2 times
      more likely to be ingested as nonalcohol food items. Planned exercise and sports
      appeared at a rate of about 2 incidents per hour. These activities rarely
      received explicit evaluation by characters. CONCLUSIONS AND IMPLICATION: Films
      frequently portray foods and exercise. These depictions have the potential to
      cultivate beliefs about normative eating and exercise behavior, suggesting a need
      for public health professionals to encourage the media to offer healthier images.

PMID- 15745654
TI  - Barriers to and motivators for healthful eating as perceived by rural and urban
      Costa Rican adolescents.
AB  - OBJECTIVE: To assess the perceptions of rural and urban Costa Rican adolescents
      about their diet and the factors they consider significant to healthful eating.
      DESIGN: Data were collected in focus group discussions. PARTICIPANTS: The study
      sample included 108 male and female adolescents aged 12 to 18 years. Adolescents
      were recruited among 7th to 11th grade students interested in taking part in the
      study. SETTING: Two urban and one rural high school in San Jose, Costa Rica.
      PHENOMENA OF INTEREST: Diet perceptions and barriers to and motivators for
      healthful eating. ANALYSIS: Data were reviewed for emerging themes, and themes
      were coded applying content analysis procedures. The conceptual model for
      understanding adolescent eating behavior, proposed by Story and colleagues,
      served as the framework for this study. RESULTS: Factors perceived as barriers to
      adopting healthful eating practices included unavailability of healthful food in
      the school environment, inadequate food choices within the family diet, and the
      peer-group notion among males and females that healthful eating by males is
      effeminate. Factors perceived as motivators included improving the nutritional
      quality of foods available at school, adoption of healthful eating practices by
      the entire family, and healthful eating becoming a peer-group social norm.
      CONCLUSIONS AND IMPLICATIONS: This study suggests that the family, peer group,
      and school environment are potential targets for nutrition interventions for
      Costa Rican adolescents, but further studies are needed to confirm this
      conclusion. Future studies should explore in depth the factors associated with
      the family's eating pattern and the influence of adolescent socialization
      patterns (particularly male) in the establishment of a healthful diet.

PMID- 15745655
TI  - Nutrition education program Nutrition Pathfinders teaches children how to make
      healthful food choices.

PMID- 15745656
TI  - Adapting a diet analysis program for an adolescent audience.

PMID- 15745657
TI  - Developing food products and enthusiastic learners.

PMID- 15745660
TI  - [Public policies and regulation of private health insurance].

PMID- 15745658
TI  - Once upon a time in America: interactive nutrition evaluation.

PMID- 15745663
TI  - Influence of pharmacists' opinions on their dispensing medicines without
      requirement of a doctor's prescription.
AB  - OBJECTIVE: To assess the influence of pharmacists' opinions on their dispensing
      medicines with a "medical prescription only" label without requiring a doctor's
      prescription. METHODS: We performed a cross-sectional study of 166 community
      pharmacies in northwest Spain. The opinions of pharmacists on the following were
      collected as independent variables through personal interview: a) physicians'
      prescribing practices; b) the pharmacist's qualifications to prescribe; c) the
      responsibility of the pharmacist regarding the dispensed drugs; d) the customer'
      qualifications for self-medication; and e) the pharmacist's perception of his or
      her own work. The dependent variable was the pharmacist's demand for a medical
      prescription for 5 drugs, which in Spain require a prescription. Multiple linear
      regression models were constructed. RESULTS: The response rate was 98.8%. A total
      of 65.9% of pharmacists reported dispensing antibiotics without a prescription.
      This percentage was 83.5% for nonsteroidal anti-inflammatory drugs, 46.3% for
      angiotensin-converting enzyme inhibitors, 13.4% for benzodiazepines, and 84.8%
      for oral contraceptives. Further results showed that pharmacists with a heavier
      workload and those who underestimated the physicians' qualifications to prescribe
      but overestimated their own qualifications to prescribe less frequently demanded
      medical prescriptions. In contrast, pharmacists who stressed the importance of
      their duty in rationalizing the consumption of drugs more frequently demanded
      medical prescriptions. CONCLUSION: Our results suggest that to increase the
      quality of dispensing: a) the importance of the pharmacist's duty in controlling
      drug consumption should be stressed; b) pharmacies' workload should be optimized;
      and c) perceptions of physicians' prescribing practices among pharmacists should
      be improved.

PMID- 15745665
TI  - [Recent history of the news coverage of violence against women in Spain, 1997
      2001].
AB  - OBJECTIVES: To explore press coverage of violence against women between 1997 and
      2001, and to analyze the temporal development of murders due to this cause in
      Spain and the social context in which these media events take place. METHODS:
      Quantitative content analyses were performed of 865 news items on violence
      against women in the Spanish newspapers El Pais, ABC and El Mundo (1997-2001).
      Absolute and relative frequencies, and relative risk (RR), 95% confidence
      intervals (95% CI), were calculated. Crude mortality rates were calculated for
      violence against women (1998-2003) based on the Register of the Federation of
      Separated and Divorced Women. RESULTS: Press coverage of violence against women
      increased, coinciding with dramatic events and political responses to the
      problem. In this context, mortality from this cause remained constant. News about
      incidents (65%) were more frequent than news about interventions (35%). In news
      items in which sex was identified (35% of the total), women (n = 151) and men (n
      = 150) shared the role of principle information source. Men from law institutions
      (RR = 1.77; 95% CI, 1.44-2.17) and women from health institutions (RR = 0.39; 95%
      CI, 0.14-1.08) and associations (RR = 0.33; 95% CI, 0.13-0.81) were more likely
      to be the main source of information than their counterparts. Men had a higher
      probability than women of being the main source of information in news about
      punishment (RR = 1.42; 95% CI, 1.12-1.81). CONCLUSIONS: In a context in which
      mortality from violence against women remains constant, news about this subject
      has increased, coinciding with dramatic events and political responses. The main
      sources of information are politicians of both sexes, men from law institutions,
      and women from health institutions and associations. Men are the main source of
      information in news about punishment.

PMID- 15745664
TI  - [Public healthcare coverage versus double healthcare coverage: what are the
      differences?].
AB  - OBJECTIVE: To identify differences in socioeconomic characteristics, health
      status, health services' utilization, and satisfaction with health services
      between the population with public healthcare coverage only and the population
      with double healthcare coverage through additional affiliation to mutual or
      private health insurance companies. METHODS: Data from the 2002 Catalan Health
      Interview Survey with interviews to 8,400 individuals were used. Individuals with
      public healthcare insurance were differentiated from those who also had private
      health insurance. Multivariate logistic regression analysis was used. RESULTS: A
      total of 99.2% of the population reported public healthcare coverage and 24.7%
      also had voluntary mutual or private insurance. Individuals with double coverage
      were younger, had a high level of education, belonged to advantaged classes, and
      reported better self-perceived health and fewer chronic diseases and
      disabilities. No significant differences in the percentage of individuals who
      reported visiting a health professional in the previous 15 days were observed.
      Significant differences in the type of professional visited were observed: 65% of
      individuals with public healthcare coverage only visited primary care settings
      but 51.1% of those with double coverage visited specialists. The proportion of
      persons reporting that they were satisfied or very satisfied with professional
      attitudes, waiting times and administrative procedures was higher in the double
      coverage group. CONCLUSIONS: Distinct sociodemographic and health profiles were
      found between persons with public coverage only and those with double coverage.
      Health services' utilization also differed between the two groups.

PMID- 15745666
TI  - [Update of the cost of needlestick injuries in hospital healthcare personnel].
AB  - OBJECTIVES: To update the mean cost of each hepatitis B, hepatitis C and HIV
      follow-up in health personnel accidentally exposed to blood and body fluids, to
      stratify the cost depending on the serological status of the source, and to
      identify the items that account for the main part of the cost. METHODS: A cost
      analysis was carried out. The postexposure program was modeled on a decision tree
      combining probabilities (percentage of each type of source depending on
      positivity for the three viruses and immunization status of the health worker
      against hepatitis B) and monetary costs (euros in 2002). Costs included salaries,
      laboratory, pharmacy (including postexposure prophylaxis), water, gas and
      electricity, cleaning, telephone, medical and office equipment, amortization and
      lost productivity. RESULTS: The mean cost was 388 euros, ranging from 1,502 euros
      (source positive for hepatitis C and HIV) to 172 euros (source negative for the
      three viruses). If the source was hepatitis B positive, the mean cost was 666
      euros when the injured worker was not immunized and was 467 euros if the worker
      was immunized. Serologic tests and postexposure prophylaxis accounted for the
      main part of the cost. CONCLUSIONS: The high cost suggests the need for
      appropriate risk evaluation to avoid unnecessary follow-ups. The model used
      allows the cost of each potentially avoidable episode to be determined and could
      be used in any hospital to perform an economic evaluation of new preventive
      devices.

PMID- 15745667
TI  - [Cognitive factors associated with smoking initiation in adolescents].
AB  - OBJECTIVE: To study the association between cognitive factors of the behavioral
      change model "Attitude Self Efficacy" (ASE) at different phases of smoking
      initiation among adolescents. METHODS: We carried out a cross-sectional survey
      among students in the second grade of Compulsory Secondary Education (13-14 years
      old) from Cornella de Llobregat (Barcelona, Spain) in 2000 to obtain information
      on cognitive factors and smoking. Logistic regression analysis was used to
      investigate the variables associated with smoking (odds ratio [OR] of
      experimenters vs. non-smokers and of smokers vs. experimenters). RESULTS: The
      prevalence of daily smoking was 22.9% (95% CI, 16.5%-29.3%) among boys and 36.2%
      (95% CI, 29.7%-42.6%) among girls. Factors associated with experimenting (vs. non
      smoking) were: attitudes to smoking (disagreement with smoke-free areas [OR =
      3.46; 95% CI, 1.65-7.24], agreement with smoking promotion [OR = 3.42; 95% CI,
      1.42-8.28]), and subjective norms (perceiving friends as smokers [OR = 2.50; 95%
      CI, 1.17-5.35]). The variables associated with regular smoking (vs experimenting)
      belong to: self-efficacy and attitudes to smoking. CONCLUSIONS: Focussing on
      subjective norms and smoking attitudes with programs targetted younger ages seems
      appropriate, since these factors are more closely associated with the
      experimenting phase. Encouraging skills to refuse cigarettes offered by friends
      is appropriate at a more advanced age, since this determinant is associated with
      the change from experimenting to regular smoking.

PMID- 15745668
TI  - [Short-term effectiveness of brief interventions in alcohol-positive traffic
      casualties].
AB  - OBJECTIVES: To investigate the effectiveness of brief interventions to reduce
      alcohol intake in traffic casualties with a positive blood alcohol concentration.
      METHODS: Nine hundred forty-eight eligible casualties (97.6% of eligible
      casualties within a universe of 1106) were screened for alcohol and 126 (13.3%)
      were identified as positive. Interventions were performed in 85, randomly
      allocated to a minimal intervention (simple advice) or a brief intervention
      (motivational intervention). Telephone follow-up was scheduled for months 3, 6
      and 12. The present study reports the results of follow-up at month 3. RESULTS:
      Fifty-seven patients (67%) were followed up at month 3. A total of 73.7% had
      reduced their alcohol intake and this percentage was greater in the group who
      underwent the brief intervention (p = 0.06; effect size 0.5) and among heavy
      drinkers (p < 0.05). CONCLUSIONS: The data indicate the effectiveness of the
      brief intervention, although the sample size does not allow definitive
      conclusions to be drawn.

PMID- 15745669
TI  - [Epidemiological aspects of dog bites].
AB  - Animal bites in humans are an important public health problem. Most of these
      bites are dog bites. The first step in preventing this kind of accident is to
      identify the associated risk factors. The present article reviews the most
      important published articles on the incidence of dog bites, their risk factors,
      and preventive measures. Concerning victim profiles, features such as age, sex,
      location, and the severity of the wounds are reviewed. Regarding dogs, the most
      frequent breeds involved and the dog's previous history of aggression are
      described. In addition, the different contexts in which bites occur are reported.
      Thus, factors such as dates, number of dogs, places, victim-dog relationship and
      interaction, and the distinct involved categories of aggression of the canine
      ethogram are reviewed. The most frequent recommendations found in the literature
      to reduce and prevent dog bites in the human population are also described.

PMID- 15745670
TI  - [Apropos of private health insurance].

PMID- 15745671
TI  - [Between consensus and scientific evidence].

PMID- 15745672
TI  - [Automatic calculation of relative survival through the web. The WAERS project of
      the Catalan Institute of Oncology].
AB  - The most commonly used measure to estimate cancer survival is relative survival,
      defined as the ratio between observed and expected survival. Expected survival is
      computed on the basis of the mortality of a reference population. Mortality
      tables for the general population are not always available and their calculation
      requires specific software. For that purpose, the Catalan Institute of Oncology
      developed WAERS (Web-Assisted Estimation of Relative Survival), a web-based
      application that estimates the relative survival for a cohort of patients. The
      user prepares data in a specific format and sends them to a remote server located
      at the Catalan Institute of Oncology. This server computes relative survival and
      returns a file with the results to the electronic address supplied by the user.
      By means of this application, hospital- and population-based Spanish cancer
      registries and registries of other diseases can estimate relative survival of
      their cohorts using their reference population (province or autonomous
      community). This application could also be useful for cohort mortality studies.

PMID- 15745674
TI  - [What can epidemiology do when faced with terrorism?].

PMID- 15745673
TI  - [A primary healthcare strategy in disaster situations].
AB  - The present article describes the experience of the Cuban Medical Team in the
      Colombian Coffee Area after the earthquake of January 25, 1999. The interventions
      were directed at the areas of primary health care, primary environmental care,
      environmental health, and epidemiological surveillance, bearing in mind the
      organization of earthquake victims sheltered in emergency settlements in the
      affected municipality. Active epidemiological surveillance showed that the main
      causes of morbidity were acute diarrheic diseases, acute respiratory infections,
      and skin diseases. Evaluation of the settlements showed a correlation between
      poor environmental health conditions and associated diseases. The results of this
      field study could serve as a guide for health professionals in the event of
      disasters and displaced populations.

PMID- 15745675
TI  - [Letter of the Executive Committee of the Network of Centers for Cooperative
      Investigation, Epidemiology and Health to mark the terrorist bombings of 11
      March].

PMID- 15745676
TI  - [On rational drug use, 50 years ago].

PMID- 15745678
TI  - [1994-2004: a key decade for Nuclear Medicine in breast cancer].

PMID- 15745679
TI  - [Early alteration of adrenergic cardiac function in parkinsonisms with Lewy
      bodies].
AB  - BACKGROUND: 123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy is
      clinically used to estimate myocardial sympathetic damage in some forms of heart
      disease, autonomic nerve disturbance in diabetic neuropathy, and disturbance of
      the autonomic nervous system in neurodegenerative disease. In the present study,
      examinations were performed to clarify the rate and characteristics of cardiac
      sympathetic disturbance in Parkinson's disease (PD) and usefulness of 123I-MIBG
      myocardial scintigraphy to differentiate PD from the Lewy Body Disease (LBD).
      MATERIAL AND METHODS: 108 subjects were studied. There were 70 patients with PD,
      21 patients with LBD, and 17 age-matched normal subjects without neurological
      disease. The clinical parameters evaluated were severity of the process (measured
      by Hoehn and Yahr Scale), vegetative manifestations, development time and use of
      medication taken. Myocardial adrenergic function was analyzed by imaging with
      123I-MIBG. Early (15 min) and delayed (4 h) images of the thorax in the anterior
      view were obtained after injection of 123I-MIBG (111 MBq). The qualitative and
      semiquantitative 123I-MIBG uptake was quantified by calculating a heart-to
      mediastinum ratio (HMR) and analyzed in a blind manner. RESULTS: The mean H/M
      ratio in patients with PD and LBD was significantly lower than in controls (p <
      0.05). This is independent of development time, process severity, use of
      medication or vegetative manifestations. The HMR obtained in LBD patients is less
      clear than in PD. CONCLUSION: 123I-MIBG myocardial scintigraphy might detect
      early disturbances of the sympathetic nervous system in PD and LBD.

PMID- 15745680
TI  - [Simultaneous location of non-palpable breast neoplasms and sentinel node (SN)
      study by radioisotopic techniques].
AB  - OBJECTIVE: To obtain correct location of non-palpable breast lesions, with high
      suspicion of malignancy and detection of SN by radiosotopic techniques. MATERIAL
      AND METHODS: Thirty-one patients whose ages ranged from 35 to 79 years, with non
      palpable breast lesions detected by mammography and/or ultrasonography were
      studied. All the patients were diagnosed of breast cancer and treated with
      primary chemotherapy. All the patients underwent total axillary dissection. At 24
      hours of the intervention, all patients received one dose of 37 MBq (1 mCi) of
      99mTc labeled macroaggregated albumin (MAA) in the center of the lesion by
      ultrasonographic guide. Scintigraphic images were performed in anterior and
      lateral projections (in prone decubitus with hanging breast) to verify the
      correct location of the radiopharmaceutical. After, a study of the SN was
      performed by subdermal administration of an 18 MBq (0.5 mCi) dose of 99mTc
      labeled nanocolloid. The SN site was labeled on the skin with indelible ink. The
      intrasurgical site of the breast lesion and SN was performed using a gamma
      detector probe. Correct placement of the intralesional radiopharmaceutical,
      existence of disease free borders and histological study of SN were performed by
      the pathologist in the surgical act. The differed pathology study was performed
      with hematoxilin-eosin and immunohistochemistry. RESULT: In 29 of the 31 lesion
      sites, there was good placement of the radiotracer (93.5 %). There was 1 case of
      contamination of the needle pathway and another that did not coincide with the
      lesion, due to poor placement. Location of the SN was 96 % in the axilla and 4 %
      in axilla and internal mammary chain. The SN was located in surgery in 28/31
      patients (90 %). CONCLUSION: Simultaneous radioguided location of the hidden
      breast lesions and sentinel node is a simple method, which is well tolerated by
      the patients and can be done in a single operation act.

PMID- 15745681
TI  - [Correlation of hematologic parameters with bone marrow and spleen uptake in FDG
      PET].
AB  - OBJECTIVE: To assess the relationship between various hematologic parameters and
      bone marrow (BM) and splenic uptake of FDG in PET imaging. MATERIAL AND METHODS:
      29 patients with Hodgkin's disease (HD) referred for baseline FDG PET imaging
      before treatment and without evidence of bone marrow (BM) involvement were
      included in the study. Splenic uptake also was analyzed in 18 patients without
      splenic involvement. BM and splenic activity were visually graded on a 3 point
      scale. Activity pattern was classified as homogeneous or heterogeneous. Semi
      quantitative analysis was also performed by drawing regions of interest (ROI)
      over the spine and spleen. ROIs also were drawn over right lung and liver. FDG
      uptake ratios for the spine and spleen in comparison with the lung and liver were
      generated. Visual scoring of marrow and splenic uptake, and the various ratios
      were correlated with hemoglobin (Hb), white blood cell (WBC), and platelet
      counts, and correlation coefficients were calculated. RESULTS: In 27/29 patients
      (93 %) BM and in 18/18 patients (100 %) spleen uptake was diffuse. There was a
      direct correlation between BM and spleen uptake of FDG with increasing WBC, which
      was stronger than the inverse correlation seen with Hb (the lower the Hb the
      greater the uptake). Correlation with platelet counts was weaker. CONCLUSION:
      There is a correlation between hematologic parameters such as Hb, WBC and
      platelet counts and the uptake of FDG in BM and spleen in PET imaging. Knowledge
      of this correlation should help to better interpret and understand PET imaging.

PMID- 15745682
TI  - [Impact of positron emission tomography with FDG-PET in treatment of patients
      with suspected recurrent ovarian cancer].
AB  - AIM: Recurrent ovarian cancer is a major problem and an accurate diagnosis can
      often change patients' management. This study aimed to assess the impact on
      management of FDG-PET in recurrent ovarian cancer. MATERIAL AND METHODS: Forty
      three patients in whom FDG-PET scan was performed due to suspected recurrent
      ovarian cancer were included. FDG-PET results were confirmed by histopathology
      and clinical follow-up of at least 12 months. To assess impact on management the
      treatment plan based on conventional imaging methods was compared with the
      treatment plan based on inclusion of PET findings, classifying FDG-PET impact on
      management as high, medium, low or no impact. Management changes, when present,
      were classified as intermodality or intramodality. RESULTS: FDG-PET had a high
      impact on therapeutic management in 28 patients (65.1 %), medium impact in 2
      patients (4.6 %), low impact in 9 patients (20.9 %), and no impact in 4 patients
      (9.3 %). FDG-PET induced an intermodality change in management in 27 patients
      (62,8 %); intramodality changes were induced in 3 patients (7 %). Finally, it
      produced no treatment changes in 13 patients (30.2 %). CONCLUSION: FDG-PET
      supplied additional information when compared to conventional diagnostic
      procedures and allowed adequate management changes in most patients.

PMID- 15745683
TI  - [18-FDG-PET in a case of recurrent malignant schwannoma].
AB  - The peripheral nerve sarcoma, also called malignant schwannoma, is originally a
      soft tissue sarcoma. It is mainly located in the peripheral sheath nerve of the
      limbs and usually infiltrates the nerve fibres. We present the case of a thirty
      year old woman with a malignant schwannoma in her left leg sciatic nerve who had
      been treated on several occasions. An 18-FDG positron emission tomography was
      performed to evaluate the management of the patient. It showed regional
      recurrence, which required leg amputation. The pathological result has confirmed
      the PET diagnosis. PET can be a useful technique to detect recurrence for this
      kind of tumor, mainly in patients who have been previously radiated when the MRI
      is insufficient to perform a differential diagnosis between postirradiation
      fibrosis and tumoral recurrence, allowing for suitable therapeutic management of
      the patient.

PMID- 15745684
TI  - [Use of intraoperative lymphoscintigraphy in doubtful cases of sentinel node
      detection].
AB  - Lymphoscintigraphy is a widely accepted method used to detect selectively the
      sentinel node in malignant melanoma. This is the case report of a patient who was
      operated on for an inguinal melanoma and who was referred to the Nuclear Medicine
      Section for preoperative lymphoscintigraphy. There were technical problems for
      sentinel node detection due to the proximity of injection points. We aimed to
      know the possibility to perform an intraoperative lymphoscintigraphy as a valid
      and useful technique in cases as this one.

PMID- 15745685
TI  - [Sigmoid colon affected by ulcerous colitis in the interior of the inguinal
      scrotal hernia. Casual finding in the scintigraphy with 99mTc HMPAO leukocytes].

PMID- 15745686
TI  - [Pleural metastasis of an osteosarcoma: scintigraphic image].

PMID- 15745687
TI  - [Present state of Positron Emission Tomography in Spain. Results of the survey].

PMID- 15745688
TI  - [Twenty years ago, a scientific, cultural and French-speaking dream!].

PMID- 15745689
TI  - [The citizen's right to scientific information and the absolute necessity of a
      major biomedical journal in French].

PMID- 15745690
TI  - [Cultured red blood cells: a new step in cell engineering].

PMID- 15745691
TI  - [Oxidative stress and angiogenesis: major role of AP-1].

PMID- 15745692
TI  - [Inhibition of endocytic recycling by Rififylin].

PMID- 15745693
TI  - [Emx2 in axons: translational functions of homeodomain transcription factors].

PMID- 15745694
TI  - [Roles of PPARdelta in skeletal muscle physiology].

PMID- 15745695
TI  - [A new role for peripheral benzodiazepine receptor?].

PMID- 15745696
TI  - [Recurrent fever in malaria: a main advantage for Plasmodium falciparum?].

PMID- 15745698
TI  - [Alternative mRNA splicing, pathology and molecular therapeutics].
AB  - Pre-mRNA splicing operates towards at least 95 % of the transcript pool. It is
      subjected to a large number of variations, collectively regrouped under the term
      of alternative mRNA splicing, which occurs, on average, 6 to 8 times per pre-mRNA
      molecule. Consequently, many more proteins may be encoded from a single gene,
      which may satisfy a physiological need, or mark a pathological adaptation. The
      identification of mutations in sequences required for splicing, both constitutive
      and alternative, or for their control, has permitted to determine the causes of
      qualitative or quantitative variations in transcript levels associated with
      inherited diseases or cancer development. A number of molecular approaches have
      been undertaken to try to compensate for the effect of deleterious splicing
      mutations and to restore, at least in part, sufficient amounts of either the
      normal or a surrogate transcript. These include overexpression of splicing
      proteins, improvement of their activity by post-translational modification,
      splice-site increased or decreased usage, and RNA-mediated trans-splicing. Using
      such approaches, phenotypic improvements have been obtained in animal models,
      carrying new hopes for the development of therapeutic strategies aimed at
      correcting both inherited and acquired diseases that involve pre-mRNA splicing
      defects.

PMID- 15745699
TI  - [Centromere elasticity].
AB  - In addition to the role in the spindle apparatus and associated motors, the
      chromosome themselves play an important role in facilitating chromosome
      segregation. Sister chromatids are joined at the centromere through a protein
      complex called cohesin. Chromatids separation requires the degradation by
      separase of specific proteins acting as a glue to form the cohesin complex. This
      evolutionally complex is required for the establishment and maintenance of sister
      chromatids in a ring like structure. It is therefore a key question whether
      cohesin is indeed a main component of active centromere. Cohesin is insufficient
      to resist the splitting force exerted by microtubules until anaphase and must be
      renforced by cohesion provided by flanking DNA. The ring model suggests that
      cohesine might possess a considerable mobility when associated with chromatin.
      Observations demonstrate that the interior region of the centromere behaves as an
      elastic element. Chromosomes display remarkable elasticity, returning to their
      initial shape after being extended by up to 10 times. For larger deformations the
      thick filament is converted in thin filament which can be stretched six times
      before breaking. This article suggests an additional and novel role for the
      protein titin on chromosome structure and dynamic. Titine was identified as a
      chromosomal component and it was hypothesised that titin may provide elasticity
      to chromosome and resistance to chromosome breakages during mitosis. The elastic
      properties of purified titin correspond well to the elastic properties of
      chromosome in living cells. The deformability and bending rigidity are consistent
      with a model developed for titin elasticity. The association of the presence of
      cohesine ring and the activity of titin could be necessary for segregation.

PMID- 15745700
TI  - [LAP proteins: new gatekeepers of epithelial homeostasis].
AB  - Cell proliferation and cell differentiation are balanced processes required for
      the correct development and maintenance of tissues, including epithelial tissues.
      Disruption of this balance by downregulation or loss of function of gatekeepers
      of epithelial homeostasis may unleash tumor suppressing activities leading
      ultimately to tumorigenesis. Among the newcoming actors involved in epithelial
      cell polarity, recent data shed light on the crucial role played by the LAP (LRR
      And PDZ) protein family. LAP proteins assemble receptors, cytoplasmic adaptors
      and enzymes in multimolecular networks important for the different steps of
      epithelial differentiation : adhesion, building of tight junctions and
      trafficking of proteins along the secretory pathway. Furthermore, genetic studies
      in invertebrates and vertebrates have installed LAP proteins not only as crucial
      determinants for epithelial integrity but also as key regulators of cell
      proliferation and embryonic development.

PMID- 15745701
TI  - [RIP140 and hormone signaling].
AB  - Nuclear hormone receptors belong to a superfamily of ligand-activated
      transcription factors which regulate fundamental physiological processes. Their
      activity is controlled by a large number of coregulatory proteins which are, in
      most cases, recruited by nuclear receptors in the presence of ligand. RIP140
      (receptor interacting protein of 140 kDa) was one of the first transcription
      cofactors to be identified almost ten years ago. This molecule is an atypical
      cofactor which interacts with agonist-liganded nuclear receptors but negatively
      regulates their transactivation potential. RIP140 exhibits nine leucine-rich
      motifs (LxxLL) which mediate the specific docking on the nuclear receptor ligand
      binding domain. Transcription repression exerted by this cofactor implicates
      different mechanisms. Not only it involves a competition with coactivators such
      as those belonging to the p160 family, but also relies on active intrinsic
      repression through at least four different domains which allow recruitement of
      downstream repressors such as histone deacetylases (HDACs) or C-terminal binding
      proteins (CtBPs). The biological role of RIP140 has been investigated by
      disrupting the gene in mice. The lack of RIP140 expression in ovaries prevents
      follicle rupture and ovulation, rising to female infertility. In addition, this
      cofactor is also required for the control of fat storage and utilization through
      the regulation of genes involved in thermogenesis. Finally, RIP140 could play a
      role in the hormonal control of cancer cell proliferation by negatively
      regulating the activity of estrogen and retinoic acid receptors which are key
      actors in cancer growth. Interestingly, both estrogens and retinoic acid regulate
      RIP140 gene expression, revealing an increased level of complexity. In
      conclusion, RIP140 is an atypical transcription inhibitor which, by repressing
      nuclear hormone receptor activity, plays fundamental physiopathological roles.

PMID- 15745702
TI  - [Structure of the calcium channel beta subunit: the place of the beta-interaction
      domain].
AB  - Voltage-gated calcium channels are key players in a number of fundamental
      physiological functions including contraction, secretion, transmitter release or
      gene activation. They allow a flux of calcium into the cell that constitutes a
      switch-on signal for most of these functions. The structures responsible for the
      shaping of these fluxes by the membrane voltage belong to the channel itself, but
      a number of associated proteins are known to more precisely tune this calcium
      entry and adapt it to the cellular demand. The calcium channel regulatory beta
      subunit is undoubtedly the most important one, being influent on the expression,
      the kinetics, the voltage-dependence of channel opening and closing and on the
      pharmacology of the channel. Heterologous expression, combined to mutagenesis and
      electrophysiological and biochemical experiments have revealed the roles of short
      sequences of the beta subunit, including the BID (beta-interaction domain), in
      the physical and functional interactions with the channel pore. The resolved
      crystal structure of the beta subunit now sheds new light on these sequences and
      their interactions with the rest of the protein. The presence of a type 3 src
      homology (SH3) domain and a guanylate kinase (GK) domain confirms that the
      subunit belongs to the MAGUK protein family. Consistently, the polyproline
      binding site and the kinase function of the SH3 and the GK domains, respectively,
      are non functional, and the BID appears to be buried in the structure, preserving
      the SH3-GK interaction but not directly available for interactions with the
      channel pore subunit. Anchoring of the beta subunit to the channel occurs via a
      hydrophobic grove in the GK domain, leaving a large surface of the subunit open
      to other protein-protein interactions. To what extent the intramolecular SH3-GK
      interaction is necessary for the stabilisation of this grove in a functional unit
      remains to be understood. The beta subunit may thus play a key role in
      scaffolding multiple proteins around the channel and organizing diverse calcium
      dependent signalling pathways directly linked to voltage-gated calcium entry.
      These findings will undoubtedly vitalize the search for new beta-specific
      partners and functions.

PMID- 15745703
TI  - [A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse].
AB  - Gamma-hydroxybutyrate (GHB) is mainly known because of its popularity as a drug
      of abuse among young individuals. However this substance increases slow-wave deep
      sleep and the secretion of growth hormone and besides its role in anaesthesia, it
      is used in several therapeutic indications including alcohol withdrawal, control
      of daytime sleep attacks and cataplexy in narcoleptic patients and is proposed
      for the treatment of fibromyalgia. GHB is also an endogenous substance present in
      several organs, including brain where it is synthesized from GABA in cells
      containing glutamic acid decarboxylase, the marker of GABAergic neurons. GHB is
      accumulated by the vesicular inhibitory aminoacid transporter (VIAAT) and
      released by depolarization via a Ca2+ dependent-mechanism. A family of GHB
      receptors exists in brain which possesses hyperpolarizing properties through Ca2+
      and K+ channels. These receptors--one of them has been recently cloned from rat
      brain hippocampus--are thought to regulate GABAergic activities via a subtle
      balance between sensitized/desensitized states. Massive absorption of GHB
      desensitize GHB receptors and this modification, together with a direct
      stimulation of GABAB receptors by GHB, induce a perturbation in GABA, dopamine
      and opiate releases in several region of the brain. This adaptation phenomenon is
      probably responsible for the therapeutic and recreative effects of exogenous GHB.

PMID- 15745704
TI  - [Expanding the known diversity and environmental distribution of cultured and
      uncultured bacteria].
AB  - Microorganisms represent the largest component of biodiversity in our biosphere.
      Traditional methods of bacterial identification depend on their culture on
      laboratory media and the comparison of their phenotypic characteristics. They
      include cellular morphology, motility, staining reactions of cell walls, ability
      to grow on different media and biochemical tests. These methods have many
      limitations and only a very small fraction of microorganisms have been
      cultivated. To date, molecular methods based on 16S rRNA sequences and their
      phylogenetic analysis are widely used for reliable identification, particularly
      for hard-to-culture microbial pathogens. These so-called << molecular methods >>
      do not require laboratory culture of isolated organisms, and many novel non
      described phyla have been detected, improving our view of bacterial diversity.
      Novel strategies for culturing the << uncultivated >> are now under development,
      which are leading to the complete characterization of these new bacteria. More
      recently, meta- or ecogenomics, based on the complete sequencing of clones
      containing cosmids or bacterial artificial chromosomes with inserts, addresses
      the genetic potential of a sample irrespective of whether the microorganisms can
      be cultured or not. This has considerably extended our view of microbial
      diversity at the genomic level and the probability of finding new genes and their
      products suitable for the biotechnological and pharmaceutical industry.

PMID- 15745705
TI  - [New advances in osteoporosis nutritional prevention].
AB  - With the human race experiencing a progressive increase in life expectancy, we
      are facing a growing prevalence of chronic age-related conditions, among which
      osteoporosis is a generalised condition of bone, whose hallmark is increased bone
      fragility. Based on the overwhelming body of evidence emphasising that gonadal
      failure at the time of menopause causes osteopenia and the administration of
      estrogens in postmenopausal women prevents this loss, hormone replacement therapy
      (HRT) has been widely recommended. However HRT should be limited due to its
      potential adverse effects. In this light, an effort should be made to integrate
      alternative therapies of proven values to provide new options for women in
      midlife. Research in nutrition over the past 30 years has led to exciting and
      significant progress. Although the primary role of diet is to provide sufficient
      nutrients to fulfill the metabolic requirements of an individual, there is an
      emerging rationale to support the hypothesis that, by modulating specific target
      functions in the body, diet can help to achieve optimal health and also play an
      important role in reducing the risk of disease. Specifically, it has been
      recognized that human diet contains, in addition to essential macro- and
      micronutrients, a complex array of naturally occurring bioactive molecules, the
      phytochemicals, that may confer significant long-term health benefits. Indeed,
      besides calcium, micronutrients such as vitamins, polyphenols, phytoestrogens,
      trace elements or minerals remain a source for putative new and innovative
      dietary health intervention in the nutritional prevention of osteoporosis.

PMID- 15745706
TI  - [On the acceptability of xenografts].
AB  - Transplantation represents a major advance in modern medicine with a major impact
      on the interactions between individuals and society. The numbers of patients
      undergoing organ transplantation increased steadily over the years and around
      250,000 individuals are living nowadays in Europe with a transplanted organ. On
      the other hand, the numbers of cadaveric (brain-dead) donors used for organ
      transplantation remains stable, at around 5,000 each year, and the numbers of
      transplantation from living donors only slowly increase in Europe. Therefore, a
      gap is growing between the numbers of patients in need of a transplant and the
      numbers of organs available for transplantation. About 45,000 patients are
      currently on renal transplant waiting lists in Europe and, depending on the
      countries considered, 15 to 30 % of candidates for liver or heart transplantation
      die before a life-saving transplant becomes available to them. There is therefore
      an urgent need to implement innovative research and to take full advantage of
      recent biotechnological advances to explore new avenues in xenotransplantation,
      and to simultaneously address the ethical, societal and public health issues
      related to organ replacement. Much progresses have been accomplished in the
      understanding of xenograft rejection processes that include hyperacute, acute
      vascular and cellular rejection mechanisms. Strategies to promote xenograft
      survival that are currently under evaluation include genetic engineering of donor
      pigs, adapted immunosuppressive treatments and tolerance induction. Also, the
      psychological acceptance has been evaluated.

PMID- 15745707
TI  - [Transduction peptides, the useful face of a new signaling mechanism].
AB  - Transduction peptides that cross the plasma membrane of live cells are commonly
      used for the in vitro and in vivo targeting of hydrophilic drugs into the cell
      interior. Although this family of peptides has recently increased and will
      probably continue to do so, the two mainly used peptides are derived from
      transcription factors. Indeed, TAT is a 12 amino acid long arginine-rich peptide
      present in the HIV transcription factor, and penetratin - or its variants -
      corresponds to 16 amino acids that define the highly conserved third helix of the
      DNA-binding domain (homeodomain) of homeoprotein transcription factors. In this
      review, we shall recall the different steps that have led to the discovery of
      transduction peptides and present the most likely hypotheses concerning the
      mechanisms involved in their internalization. At the risk of being incomplete or,
      even, biased, we shall concentrate on penetratins and TAT. The reason is that
      these peptides have been studied for over ten years leading to the edification of
      robust knowledge regarding their properties. This attitude will not preclude
      comparisons with other peptides, if necessary. Our goal is to describe the mode
      of action of these transduction peptides, their range of activity in term of cell
      types that accept them and cargoes that they can transport, and, also, some of
      the limitations that one can encounter in their use. Finally, based on the idea
      that peptide transduction is the technological face of a physiological property
      of some transcription factors, we shall discuss the putative physiological
      function of homeoprotein transduction, and, as a consequence, the possibility to
      use these factors as therapeutic proteins.

PMID- 15745708
TI  - [Mechanisms of placebo effect and of conditioning: neurobiological data in human
      and animals].
AB  - A placebo is a sham treatment such as pill, liquid, injection, devoid of
      biological activity and used in pharmacology as a control for the activity of a
      drug. In many cases, this placebo induces biological or psychological effects in
      the human. Two theories have been proposed to explain the placebo effect: the
      conditioning theory which states that the placebo effect is a conditioned
      response, and the mentalistic theory for which the patient expectation is the
      primary basis of the placebo effect. The mechanisms involved in these processes
      are beginning to be understood through new techniques of investigation in
      neuroscience. Dopamine and endorphins have been clearly involved as mediators of
      the placebo effect. Brain imaging has demonstrated that the placebo effect
      activates the brain similarly as the active drug and in the same brain area. This
      is the case for a dopamine placebo in the Parkinson'disease, for analgesic
      caffeine- or antidepressor-placebo in the healthy subject. It remains to be
      understood how conditioning and expectancy are able to activate, in the brain,
      memory loops that reproduce the expected biological response.

PMID- 15745709
TI  - [Eugenist politics in the United States of America in the first xxth half
      century].
AB  - The United-States were the first country which had devised eugenist politics. The
      applications of theories had taken place as far as the end of the 1960's. They
      were placed one's reliance on two points: on the one hand, immigration's
      limitation and on the other hand an obligatory sterilisation of criminels and
      feebleminde people.

PMID- 15745710
TI  - [All artificial procreations are in nature].

PMID- 15745711
TI  - [The new worldwar].

PMID- 15745712
TI  - [A debate about clinical ethics].

PMID- 15745713
TI  - The Vioxx debacle.

PMID- 15745714
TI  - The diabetic lung: relevance of alveolar microangiopathy for the use of inhaled
      insulin.
AB  - The alveolar-capillary network receives the entire cardiac output and constitutes
      the largest microvascular organ in the body, making it highly susceptible to
      systemic microangiopathy. Owing to its large reserves, symptoms and disability
      develop later in the lung than in smaller microvasculature such as the kidney or
      retina despite a comparable severity of anatomic involvement. Hence, pulmonary
      impairment in diabetes mellitus is under-recognized. Nonetheless, respiratory
      autonomic neuropathy and structural derangement of the thorax and lung parenchyma
      develop in many asymptomatic diabetic patients; the pathophysiology parallels
      that in other target organs. Even subclinical loss of alveolar microvascular
      reserves can be quantified noninvasively from lung diffusing capacity and its
      components (membrane diffusing capacity and alveolar-capillary blood volume)
      measured at a given cardiac output at rest or during exercise. The alveolar
      diffusion-perfusion relation tracks the recruitment of microvascular reserves in
      a manner independent of physical fitness. This article addresses the importance
      and pathophysiologic basis of diabetic pulmonary involvement, the assessment of
      diabetic alveolar microangiopathy, and the relevance of this understanding for
      the emerging use of inhaled insulin.

PMID- 15745715
TI  - Toxoplasmosis in pregnancy.
AB  - Pregnant women who acquire infection from Toxoplasma gondii usually remain
      asymptomatic, although they can still transmit the infection to their fetuses
      with severe consequences. Given the asymptomatic nature of most Toxoplasma
      infections, primary prevention in pregnant women may lower the risk of congenital
      toxoplasmosis. Both consumption of undercooked meat and unprotected contact with
      soil are independent risk factors for T. gondii seroconversion during pregnancy,
      while contact with cat litter may pose a risk in certain situations. However,
      many pregnant women lack knowledge of these risk factors. This article reviews
      toxoplasmosis infection in pregnancy, with an emphasis on risk factors and
      appropriate counseling of pregnant women.

PMID- 15745716
TI  - Ring around the collar area.

PMID- 15745717
TI  - A 57-year-old man with a 6-day headache and fatigue.

PMID- 15745718
TI  - An 18-year-old man with peculiar QRS complexes.

PMID- 15745719
TI  - Risk of endocarditis among patients with prosthetic valves and Staphylococcus
      aureus bacteremia.
AB  - PURPOSE: Staphylococcus aureus is a common cause of bacteremia and of native
      valve infective endocarditis. However, the risk of endocarditis in patients with
      a prosthetic valve who develop S. aureus bacteremia is unclear. The aim of this
      study was to define the risk of prosthetic valve endocarditis in patients with S.
      aureus bacteremia. SUBJECTS AND METHODS: All patients with a prosthetic valve or
      ring who developed S. aureus bacteremia during the 94-month study period were
      prospectively evaluated. The modified Duke criteria were used for the diagnosis
      of endocarditis. Patients were followed up for 12 weeks after the initial
      diagnosis of S. aureus bacteremia. RESULTS: The overall rate of definite
      prosthetic valve endocarditis among the study patients was 26/51 (51%). The risk
      of endocarditis was similar in patients with late (>or=12 months after valve
      implantation) vs. early S. aureus bacteremia (<12 months after prosthetic valve
      implantation) (50% vs. 52%, P=1.0), mitral vs. aortic prostheses (62% vs. 48%,
      P=0.24), and mechanical vs. bioprosthetic valves (62% vs. 44%, P=0.29). The 12
      week mortality was higher among patients with definite vs. possible endocarditis
      (62% vs. 28%, P=0.019). CONCLUSION: In this investigation, approximately half of
      all patients with prosthetic valves who developed S. aureus bacteremia had
      definite endocarditis. The risk of endocarditis was independent of the type,
      location, or age of the prosthetic valve. The mortality of prosthetic valve
      endocarditis is high. All patients with a prosthetic valve who develop S. aureus
      bacteremia should be aggressively screened and followed for endocarditis.

PMID- 15745721
TI  - Association between fish consumption and all-cause and cause-specific mortality
      in Japan: NIPPON DATA80, 1980-99.
AB  - PURPOSE: Although high consumption of fish may be one of the contributing factors
      for Japanese longevity, no epidemiological study using Japanese data has tested
      this hypothesis. SUBJECTS AND METHODS: The relationship between fish consumption
      and all-cause as well as cause-specific mortality was analyzed using the database
      of NIPPON DATA80. At baseline in 1980, history, physical, and blood biochemical
      measurement and a nutritional survey by the food-frequency method were performed
      in randomly selected community-based subjects aged 30 years and over in Japan.
      After exclusion of subjects with significant comorbidities at baseline, we
      followed 3945 men and 4934 women for 19 years. Men and women were analyzed
      comprehensively. Age- and sex-adjusted and multivariate adjusted relative risk
      for all-cause or cause-specific mortality was calculated using a Cox proportional
      hazards model with delayed entry. RESULTS: During 19 years of followup, there
      were 1745 deaths. Subjects were divided into 5 groups according to fish
      consumption frequency. The multivariate Cox analyses showed that relative risks
      for subjects who ate fish more than twice daily compared with those of subjects
      who ate 1 to 2 times weekly were 0.99 (95% confidence intervals: 0.77-1.27) for
      all-cause, 1.26 (0.70-2.29) for stroke, 0.92 (0.20-4.23) for cerebral hemorrhage,
      1.09 (0.48-2.43) for cerebral infarction, and 0.91 (0.35-2.35) for coronary heart
      disease mortality. CONCLUSION: Our results did not provide evidence in support of
      the fish hypothesis, perhaps because the majority of the Japanese subjects in the
      study ate fish more than the threshold level shown to be beneficial in the
      previous studies.

PMID- 15745720
TI  - Diagnosis of infectious endocarditis in patients undergoing valve surgery.
AB  - PURPOSE: Histologic examination of valve samples is considered as the gold
      standard for the diagnosis of infectious endocarditis. Molecular tools are also
      very promising for patients with negative-culture endocarditis. Thus, we studied
      the contribution of valvular histology, culture, and 16S rRNA PCR amplification
      plus sequencing to the diagnosis of infectious endocarditis in patients
      undergoing valve surgery. SUBJECTS AND METHODS: We performed culture,
      histological examination, and broad-range PCR amplification plus sequencing on
      valve samples taken from 127 patients with infectious endocarditis and from 118
      patients without endocarditis. The sensitivity and specificity of these tests for
      the diagnosis of endocarditis in patients undergoing valve surgery were studied.
      RESULTS: The sensitivity of PCR was of 61% (64/105) whereas that of histological
      examination was of 63% (62/98) and that of valve culture was of only 13%
      (14/105). All 68 positive PCR results considered reliable according to an
      interpretation scheme were from patients with infectious endocarditis, resulting
      in a 100% (118/118) specificity of the interpreted molecular approach. The
      specificity of histology was also of 100% (118/118) when using stringent criteria
      (ie, presence of vegetation, microorganisms, and/or valvular inflammation with
      mainly polymorphonuclear cells). PCR identified an etiological agent in 38%
      (5/13) of definite blood culture-negative infectious endocarditis. CONCLUSION: We
      show that valvular histology with stringent criteria is the gold standard for the
      diagnosis of infectious endocarditis. Broad-range amplification of 16S rRNA gene
      is indicated for infectious endocarditis of unknown etiology, whereas valve
      culture is of limited sensitivity.

PMID- 15745722
TI  - Thalidomide for the treatment of resistant cutaneous lupus: efficacy and safety
      of different therapeutic regimens.
AB  - PURPOSE: Thalidomide is effective for the treatment of severe cutaneous lupus.
      Our aim was to study the safety and efficacy of different doses of thalidomide in
      this condition. METHODS: We studied patients with severe cutaneous lupus that was
      unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and
      cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n =
      17), or 50 mg on alternate days (n = 15) were compared. The response to
      thalidomide was categorized as complete remission, partial remission, or no
      visible improvement. All patients received a baseline electromyogram (EMG)
      followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms
      developed. RESULTS: Forty-eight patients (46 female; mean [+/- SD] age, 44 +/- 12
      years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous
      lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24)
      were included. The response rate was 81%, including 29 patients (60%) in complete
      remission and 10 (21%) in partial remission. Nine patients (19%) failed to
      respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG
      proven in 11, including 4 patients in the 50-mg alternate-day group. Other side
      effects included drowsiness, constipation or abdominal pain, and amenorrhea. The
      relapse rate after stopping thalidomide was 67% (26/39). There was no association
      between a positive response to the drug and either starting doses or cumulative
      dose. Similarly, no association was found between peripheral neuropathy and the
      starting or cumulative dose. CONCLUSION: Thalidomide is effective for the
      treatment of severe cutaneous lupus. There were no clear dose-dependent effects.
      However, the high incidence of neurotoxicity, even at low doses, suggests that it
      may be most useful as a remission-inducing drug.

PMID- 15745723
TI  - The incidence of adverse drug events in two large academic long-term care
      facilities.
AB  - PURPOSE: To assess the incidence of and risk factors for adverse drug events in
      the long-term care setting. METHODS: We performed a cohort study of all long-stay
      residents of two academic long-term care facilities over a period of up to 9
      months during 2000 to 2001. We assessed the number of adverse drug events, the
      severity of events (classified as less serious, serious, life threatening, or
      fatal), and whether the events were preventable. A case-control study was nested
      within the prospective study to identify resident-level risk factors for the
      occurrence of adverse drug events. RESULTS: There were 815 adverse drug events,
      of which 42% were judged preventable. The overall rate of adverse drug events was
      9.8 per 100 resident-months, with a rate of 4.1 preventable adverse drug events
      per 100 resident-months. Errors associated with preventable events occurred most
      often at the stages of ordering and monitoring. Residents taking medications in
      several drug categories were at increased risk of a preventable adverse event. In
      multivariate analyses, the adjusted odds ratio was 3.4 (95% confidence interval
      [CI]: 2.0 to 5.9) for those taking antipsychotic agents, 2.8 (95% CI: 1.6 to 4.7)
      for those taking anticoagulants, 2.2 (95% CI: 1.2 to 4.0) for those taking
      diuretics, and 2.0 (95% CI: 1.1 to 3.7) for those taking antiepileptics.
      CONCLUSION: Our findings reinforce the need for a special focus on the ordering
      and monitoring stages of pharmaceutical care for preventing adverse drug events
      in the long-term care setting. Patients taking antipsychotic agents,
      anticoagulants, diuretics, and antiepileptics are at increased risk.

PMID- 15745724
TI  - Fluoroquinolone prescribing in the United States: 1995 to 2002.
AB  - PURPOSE: To measure changes in the rate and type of fluoroquinolones prescribed
      in the United States from 1995 to 2002. METHODS: We performed a longitudinal
      analysis of the National Ambulatory Medical Care Survey and the National Hospital
      Ambulatory Medical Care Survey of adult visits to physicians in ambulatory
      clinics and emergency departments throughout the United States from 1995 to 2002.
      The main outcomes were fluoroquinolone prescribing rates and prescribing in
      accordance with Food and Drug Administration approval as of December 2002.
      RESULTS: Between 1995 and 2002, fluoroquinolones became the most commonly
      prescribed class of antibiotics to adults in the United States. Fluoroquinolone
      prescribing rose threefold, from 7 million visits in 1995 to 22 million visits in
      2002 (P < 0.0001). Fluoroquinolone prescribing increased as a proportion of
      overall antibiotic prescribing (from 10% to 24%; P < 0.0001) and as a proportion
      of the U.S. population (from 39 to 106 prescriptions per 1000 adults; P < 0.001).
      These increases were due to the use of newer fluoroquinolones with activity
      against Streptococcus pneumoniae. Forty-two percent of fluoroquinolone
      prescriptions were for nonapproved diagnoses. Among patients receiving
      antibiotics, nonapproved fluoroquinolone prescribing increased over time (odds
      ratio = 1.18 per year; 95% confidence interval: 1.13 to 1.24). CONCLUSION:
      Fluoroquinolone prescribing increased threefold in outpatient clinics and
      emergency departments in the United States from 1995 to 2002. Fluoroquinolones
      became the most commonly prescribed class of antibiotics to adults in 2002.
      Nonapproved fluoroquinolone prescribing was common and increased over time. Such
      prescribing patterns are likely to be followed by an increasing prevalence of
      fluoroquinolone-resistant bacteria.

PMID- 15745725
TI  - Post-myocardial infarction smoking cessation counseling: associations with
      immediate and late mortality in older Medicare patients.
AB  - PURPOSE: To assess the difference in immediate (30 and 60 days after admission)
      and late (2-year) mortality between those who received inpatient post-myocardial
      infarction smoking cessation counseling and those who did not receive counseling.
      METHODS: We conducted an observational study of a national random sample of
      inpatients from 2971 U.S. acute care hospitals participating in the Cooperative
      Cardiovascular Project in 1994-95. Medicare beneficiaries who were current
      smokers over age 65, admitted with a documented acute myocardial infarction, and
      who were discharged to home were included (n=16743). Our main outcome measures
      were early (30-, 60-day) and late (1-, 2-year) mortality. RESULTS: Smoking
      cessation counseling was documented during their index hospitalization for 41% of
      patients. Compared with those not counseled, those who received inpatient
      counseling had lower 30-day (2.0% vs. 3.0%), 60-day (3.7% vs. 5.6%), and 2-year
      mortality (25.0% vs. 30%) (logrank P <0.0001). After adjustment for demographic
      characteristics, comorbid conditions, APACHE score, and receipt of treatments
      including aspirin, reperfusion, beta-blockers, and angiotensin-converting enzyme
      inhibitors, those receiving counseling were less likely to die within 1 year, but
      the effect was lost between 1 and 2 years [hazard ratio (HR) = 0.99 (0.91-1.10)].
      The greatest reduction in relative hazard (19%) was seen within 30 days [HR =
      0.81 (95% confidence interval 0.65-0.99)]. CONCLUSION: Immediate and long-term
      mortality rates were lower among those receiving inpatient smoking cessation
      counseling.

PMID- 15745726
TI  - A randomized trial of a primary care-based disease management program to improve
      cardiovascular risk factors and glycated hemoglobin levels in patients with
      diabetes.
AB  - PURPOSE: To assess the efficacy of a pharmacist-led, primary care-based, disease
      management program to improve cardiovascular risk factors and glycated hemoglobin
      (A(1C)) levels in vulnerable patients with poorly controlled diabetes. METHODS: A
      randomized controlled trial of 217 patients with type 2 diabetes and poor
      glycemic control (A(1C) level >or=8.0%) was conducted at an academic general
      medicine practice from February 2001 to April 2003. Intervention patients
      received intensive management from clinical pharmacists, as well as from a
      diabetes care coordinator who provided diabetes education, applied algorithms for
      managing glucose control and decreasing cardiovascular risk factors, and
      addressed barriers to care. Control patients received a one-time management
      session from a pharmacist followed by usual care from their primary care
      provider. Outcomes were recorded at baseline and at 6 and 12 months. Primary
      outcomes included blood pressure, A(1C) level, cholesterol level, and aspirin
      use. Secondary outcomes included diabetes knowledge, satisfaction, use of
      clinical services, and adverse events. RESULTS: For the 194 patients (89%) with
      12-month data, the intervention group had significantly greater improvement than
      did the control group for systolic blood pressure (-9 mm Hg; 95% confidence
      interval [CI]: -16 to -3 mm Hg) and A(1C) level (-0.8%; 95% CI: -1.7% to 0%).
      Change in total cholesterol level was not significant. At 12 months, aspirin use
      was 91% in the intervention group versus 58% among controls (P <0.0001).
      Intervention patients had greater improvements in diabetes knowledge and
      satisfaction than did control patients. There were no significant differences in
      use of clinical services or adverse events. CONCLUSION: Our comprehensive disease
      management program reduced cardiovascular risk factors and A(1C) levels among
      vulnerable patients with type 2 diabetes and poor glycemic control.

PMID- 15745727
TI  - Seasonality of invasive pneumococcal disease: temporal relation to documented
      influenza and respiratory syncytial viral circulation.
AB  - BACKGROUND: Seasonal fluctuation in the incidence of invasive pneumococcal
      disease has been attributed to winter virus exposure (e.g., influenza and
      respiratory syncytial virus [RSV]). Evidence of a direct correlation of invasive
      pneumococcal disease with laboratory-confirmed virus seasons, however, is
      limited. Using two prospective surveillance networks, the temporal relation
      between invasive pneumococcal disease and isolation of circulating winter viruses
      was explored. METHODS: Episodes of invasive pneumococcal disease in five
      Tennessee counties were collected prospectively from January 1995 through June
      2002. Virus seasons were defined using prospective laboratory-based surveillance.
      Correlation between weekly identification of invasive pneumococcal disease and
      laboratory isolation of RSV and influenza, as well as comparisons of the
      frequencies of invasive pneumococcal disease episodes during viral and nonviral
      seasons were determined. RESULTS: A total of 4147 invasive pneumococcal disease
      episodes were identified. Weekly frequency of invasive pneumococcal disease
      correlated directly with the weekly frequency of isolation of RSV (r = 0.56, P
      <0.001) and influenza (r= 0.40, P <0.001). The average weekly frequency of
      invasive pneumococcal disease during RSV and influenza seasons was higher than
      during the nonviral seasons (P <0.001 for each year). CONCLUSION: Weekly episodes
      of invasive pneumococcal disease correlated temporally with laboratory-confirmed
      weekly isolation of RSV and influenza, and the incidence of invasive pneumococcal
      disease was increased when these viruses were circulating in the community.

PMID- 15745728
TI  - Routine human immunodeficiency virus testing: an economic evaluation of current
      guidelines.
AB  - BACKGROUND: The Centers for Disease Control and Prevention guidelines recommend
      human immunodeficiency virus (HIV) counseling, testing, and referral for all
      patients in hospitals with an HIV prevalence of >or=1%. The 1% screening
      threshold has not been critically examined since HIV became effectively treatable
      in 1995. Our objective was to evaluate the clinical effect and cost-effectiveness
      of current guidelines and of alternate HIV prevalence thresholds. METHODS: We
      performed a cost-effectiveness analysis using a computer simulation model of HIV
      screening and disease as applied to inpatients in U.S. hospitals. RESULTS: At an
      undiagnosed inpatient HIV prevalence of 1% and an overall participation rate of
      33%, HIV screening increased mean quality-adjusted life expectancy by 6.13 years
      per 1000 inpatients, with a cost-effectiveness ratio of 35,400 dollars per
      quality-adjusted life-year (QALY) gained. Expansion of screening to settings with
      a prevalence as low as 0.1% increased the ratio to 64,500 dollars per QALY
      gained. Increasing counseling and testing costs from 53 dollars to 103 dollars
      per person still yielded a cost-effectiveness ratio below 100,000 dollars per
      QALY gained at a prevalence of undiagnosed infection of 0.1%. CONCLUSION: Routine
      inpatient HIV screening programs are not only cost-effective but would likely
      remain so at a prevalence of undiagnosed HIV infection 10 times lower than
      recommended thresholds. The current HIV counseling, testing, and referral
      guidelines should now be implemented nationwide as a way of linking infected
      patients to life-sustaining care.

PMID- 15745729
TI  - Physical symptoms as a predictor of health care use and mortality among older
      adults.
AB  - PURPOSE: To describe the patterns of physical symptoms in older adults and to
      examine the validity of symptoms in predicting hospitalization and mortality.
      SUBJECTS AND METHODS: Adults aged 60 years and older (N=3498) who completed
      screening for self-reported symptoms at routine primary care visits. Self
      reported symptoms were collected using an abbreviated PRIME-MD screening
      instrument. Clinical characteristics, hospitalization, and mortality in the year
      following screening were measured using data taken from a comprehensive
      electronic medical record. RESULTS: The mean patient age was 69 years, 69% were
      women, and 56% were African-American. A majority (51%) of respondents
      characterized their health as fair or poor. The most commonly reported symptoms
      were musculoskeletal pain (65%), fatigue (55%), back pain (45%), shortness of
      breath (41%), and difficulty sleeping (38%). A summary score of physical symptoms
      (range 0-12) was a significant independent predictor of future hospitalization
      and death even when controlling for clinical characteristics, chronic medical
      conditions, self-rated health, and affective symptoms. Disease-specific symptoms
      were more common among patients diagnosed with the specific condition but there
      was also a substantial background prevalence of these symptoms. CONCLUSION:
      Physical symptoms are highly prevalent in older primary care patients and predict
      hospitalization and mortality at one year. Future work is needed to determine how
      to target symptoms as a potential mechanism to reduce health care use and
      mortality.

PMID- 15745730
TI  - Psychoactive drugs, alcohol, and severe hypoglycemia in insulin-treated diabetes:
      analysis of 141 cases.

PMID- 15745731
TI  - Spontaneous and reflex movements in 107 patients with brain death.

PMID- 15745732
TI  - Crafting an effective strategic plan for a department of medicine.

PMID- 15745733
TI  - Underdiagnosed amyloidosis: amyloidosis of lysozyme variant.

PMID- 15745734
TI  - The general internist: pride and prejudice.

PMID- 15745735
TI  - Thyroid function, pulmonary arterial hypertension and scleroderma.

PMID- 15745736
TI  - Discrimination between closed and open forms of lipases using electrophoretic
      techniques.
AB  - The enhanced catalytic activity of lipases is often associated with structural
      changes. The three-dimensional (3D) structures showed that the covalently
      inhibited lipases exist under their open conformations, in contrast to their
      native closed forms. We studied the inhibition of various lipases--human and dog
      gastric lipases, human pancreatic lipase, and Humicola lanuginosa lipase--by the
      octyl-undecyl phosphonate inhibitor, and we measured the subsequent modifications
      of their respective electrophoretic mobility. Furthermore, the experimental
      values of the isoelectric points found for the native (closed) and inhibited
      (open) lipases are in agreement with theoretical calculations based on the
      electrostatic potential. We concluded that there is a significant difference in
      the isoelectric points between the closed (native) and open (inhibited)
      conformations of the four lipases investigated. Thus, analysis of the
      electrophoretic pattern is proposed as an easy experimental tool to differentiate
      between a closed and an open form of a given lipase.

PMID- 15745737
TI  - Determination of polyamines in human tissues by precolumn derivatization with 9
      fluorenylmethyl chloroformate and high-performance liquid chromatography.
AB  - A high-performance liquid chromatography (HPLC) assay with fluorescence detection
      was developed for the determination of the polyamines putrescine, spermidine,
      spermine in samples of human spinal cord, cerebellum, cerebrospinal fluid (CSF),
      skeletal muscle, and muscle microdialysates without an extensive sample
      preparation. The precolumn derivatization was performed with 9-fluorenylmethyl
      chloroformate (FMOC), and the derivatizated polyamines were stable for at least
      14 h at 4 degrees C. All polyamines were separated within 35 min. The method was
      checked for linearity, and mean correlation coefficient values of 0.995, 0.999,
      and 0.991 were achieved for putrescine, spermidine, and spermine, respectively.
      The within- and between-assay coefficient of variation percentages evaluated in
      standard solutions varied between 1.0 and 4.9% and between 1.3 and 6.9%,
      respectively. The corresponding values obtained in samples of human spinal cord
      were between 1.0 and 5.0% and between 0.6 and 5.8%. The values of the recovery,
      evaluated in spinal cord tissue, varied between 83.7 and 93.5%.

PMID- 15745738
TI  - Thiophilic paramagnetic particles as a batch separation medium for the
      purification of antibodies from various source materials.
AB  - A preparation of thiophilic agarose-based paramagnetic particles (T-Gel) has been
      developed with physical characteristics (particle size and particle density) that
      facilitate its use as a batch separation medium suitable for the large-scale
      purification and isolation of immunoglobulins. The medium was used to extract
      immunoglobulins from a wide range of starting materials, including sera, ascites
      fluid, tissue culture medium, and whole blood. None of these starting materials
      required pretreatment such as clarification by centrifugation or filtration prior
      to antibody extraction. The antibody purity obtained using T-Gel compared well
      with that obtained using protein A agarose column chromatography. Yields were
      approximately 30 mg of immunoglobulins per milliliter of T-Gel, and little was
      required in the way of specialist equipment. The method is uncomplicated and
      involves a roll mix extraction overnight, followed by magnetic separation to
      facilitate supernatant removal and subsequent washing of the particles. Elution
      of bound antibodies was carried out at neutral pH to yield a concentration of
      immunoglobulins that was approximately 7 mg/ml. The method was found to be
      applicable to antibody purification from the blood serum of seven different
      mammalian species and for all immunoglobulin classes.

PMID- 15745739
TI  - Use of multiplex polymerase chain reactions to indicate the accuracy of the
      annealing temperature of thermal cycling.
AB  - A condition for multiplex polymerase chain reactions (PCRs) of which outcomes
      sensitively indicate the actual annealing temperature of thermal cycling is
      reported. The multiplex reaction was designed to produce four different amplicons
      of 200, 300, 400, and 480 bp. However, the degree of amplification of each
      amplicon sensitively responds to a small change in the annealing temperature, by
      which one can predict the actual annealing temperature of thermal cycling.
      Deviations between the actual and the designated annealing temperatures as small
      as 0.5 degrees C were manifested by the banding patterns of the multiplex PCRs in
      simple agarose gel electrophoresis. For prediction of temperatures in a more
      objective manner, capillary electrophoresis was also applied to obtain numerical
      expressions of the relative intensities of the amplicons. By optimizing the
      multiplex PCR conditions, where concentrations of buffer, dNTPs, and primer pairs
      were major factors, satisfactory sensitivity and reproducibility of the band
      patterning were achieved. Blind tests demonstrated the accuracy of the prediction
      of actual annealing temperatures within +/-0.5 degrees C. The multiplex PCR
      approach will be further refined and tested for realization of an easily
      accessible alternative to a physical temperature measurement device in testing
      the performance of thermal cyclers for PCR.

PMID- 15745740
TI  - Characterization of advanced glycation end products for biochemical studies: side
      chain modifications and fluorescence characteristics.
AB  - Advanced glycation end products (AGEs) are known to be involved in the
      pathogenesis of several diseases and therefore effects of AGEs on cells are the
      objective of numerous investigations. Since AGEs used in biochemical studies are
      usually not chemically characterized, comparison of data is difficult if not
      impossible. To find a suitable characterization protocol, human serum albumin was
      reacted with different concentrations of glucose, methyl glyoxal, and glyoxylic
      acid. The obtained AGEs were characterized with respect to the extent of side
      chain modifications (lysine and arginine), the carboxymethyl lysine and carbonyl
      content, and the fibrillar state. Additionally, their fluorescence and absorbance
      characteristics were extensively studied. Although we found significant
      differences in the degree of modification and in AGE-specific fluorescence when
      using different modifiers, the results provide important information and allow
      comparing AGEs derived from different modifier concentrations. The results also
      suggest strong conformational changes within the modified proteins. In the
      present paper we propose a set of parameters that is sufficient to partially
      characterize AGEs used for biochemical studies.

PMID- 15745741
TI  - Activity assay of mammalian 2-cys peroxiredoxins using yeast thioredoxin
      reductase system.
AB  - 2-Cys peroxiredoxin (Prx) is a novel cellular peroxidase that reduces peroxides
      in the presence of thioredoxin, thioredoxin reductase, and nicotinamide adenine
      dinucleotide phosphate (NADPH) and that functions in H(2)O(2)-mediated signal
      transduction. Recent studies have shown that 2-cys Prx can be inactivated by
      cysteine overoxidation in conditions of oxidative stress. Therefore, peroxidase
      activity, rather than the protein level, of 2-cys Prx is the more important
      measure to predict its cellular function. Here, we introduce a modified activity
      assay method for mammalian 2-cys Prx based on yeast nonselenium thioredoxin
      reductase. Yeast thioredoxin reductase is expressed in Escherichia coli cells and
      purified at high yield (40 mg/L of culture broth) as an active flavoprotein by
      combined diethyl aminoethyl (DEAE) and phenyl hydrophobic chromatography. The
      optimal concentrations of yeast thioredoxin and thioredoxin reductase required to
      achieve maximum mammalian 2-cys Prx activity are 3.0 and 1.5 microM,
      respectively. This modified assay method is useful for measuring 2-cys Prx
      activity in cell lysates and can also be adapted for a 96-well plate reader for
      high-throughput screening of chemical compounds that target 2-cys Prx.

PMID- 15745742
TI  - Detection of small differences in actomyosin function using actin labeled with
      different phalloidin conjugates.
AB  - This study shows that there is only a negligible difference in actomyosin
      function in the in vitro motility assay among actin filaments labeled with
      Rhodamine phalloidin (RhPh), Alexa-488 phalloidin (APh), and biotin-XX phalloidin
      (BPh). Similar results were obtained at varying ionic strengths (0.02-0.13 M), in
      the presence of imidazole or 3-[N-morpholino]propanesulfonic acid (MOPS) buffer,
      and at varying MgATP concentrations (0.1-3 mM). If RhPh- and APh-labeled
      filaments were studied in a given flow cell, there was minimal variability in
      sliding velocity between the fluorophores (standard deviation of 3% of the
      absolute sliding velocity). The variability was considerably smaller than that
      between flow cells, allowing us to use dual labeling of different actin types and
      then apply analysis of variance to detect minor functional differences between
      them. Using this method, we could statistically verify a 4% difference (P<0.001)
      in sliding velocity (3mM Mg ATP) between cardiac and skeletal muscle actin.
      Suggested improvements of the method would readily allow the detection of even
      smaller differences. We discuss implications of the results for nanotechnological
      applications, understanding actomyosin function, and reducing experimental costs
      and the use of laboratory animals.

PMID- 15745743
TI  - Development of a mechanism-based assay for tissue transglutaminase--results of a
      high-throughput screen and discovery of inhibitors.
AB  - Tissue transglutaminase (TGase) is a Ca(2+)-dependent enzyme that catalyzes cross
      linking of intracellular proteins through a mechanism that involves isopeptide
      bond formation between Gln and Lys residues. In addition to its transamidation
      activity, TGase can bind guanosine 5'-triphosphate (GTP) and does so in a manner
      that is antagonized by calcium. Once bound, GTP undergoes hydrolysis to form
      guanosine 5'-diphosphate and inorganic phosphate. TGase is thought to play a
      pathogenic role in neurodegenerative diseases by promoting aggregation of disease
      specific proteins that accumulate in these disorders. Thus, this enzyme
      represents a viable target for drug discovery. We now report the development of a
      mechanism-based assay for TGase and the results of a screen using this assay in
      which we tested 56,500 drug-like molecules for their ability to inhibit TGase. In
      this assay, the Gln- and Lys-donating substrates are N,N-dimethylated casein
      (NMC) and N-Boc-Lys-NH-CH(2)-CH(2)-NH-dansyl (KXD), respectively. Through a
      combination of steady state kinetic experiments and reaction progress curve
      simulations, we were able to calculate values for the initial concentrations of
      NMC, KXD, and Ca(2+) that would produce a steady state situation in which all
      thermodynamically significant forms of substrate-bound TGase exist in equal
      concentration. Under these conditions, the assay is sensitive to both competitive
      and mixed active-site inhibitors and to inhibitors that bind to the GTP site. The
      assay was optimized for automated screening in 384-well format and was then used
      to test our compound library. From among these compounds, 104 authentic hits that
      represent several mechanistic classes were identified.

PMID- 15745744
TI  - Selective ligand purification using high-performance affinity beads.
AB  - Since the development of affinity chromatography, affinity purification
      technology has been applied to many aspects of biological research, becoming an
      indispensable tool. Efficient strategies for the identification of biologically
      active compounds based on biochemical specificity have not yet been established,
      despite widespread interest in identifying chemicals that directly alter
      biomolecular functions. Here, we report a novel method for purifying chemicals
      that specifically interact with a target biomolecule using reverse affinity
      beads, a receptor-immobilized high-performance solid-phase matrix. When FK506
      binding protein 12 (FKBP12) immobilized beads were used in this process, FK506
      was efficiently purified in one step either from a mixture of chemical compounds
      or from fermented broth extract. The reverse affinity beads facilitated
      identification of drug/receptor complex binding proteins by reconstitution of
      immobilized ligand/receptor complexes on the beads. When FKBP12/FK506 and
      FKBP12/rapamycin complexes were immobilized, calcineurin and FKBP/rapamycin
      associated protein were purified from a crude cell extract, respectively. These
      data indicate that reverse affinity beads are powerful tools for identification
      of both specific ligands and proteins that interact with receptor/ligand
      complexes.

PMID- 15745745
TI  - Lectin immunoassays using antibody fragments to detect glycoforms of human
      chorionic gonadotropin secreted by choriocarcinoma cells.
AB  - Immobilized antibodies are commonly used to recognize and bind proteins of
      interest from heterogeneous samples; however, subsequent probing of the glycan(s)
      of captured glycoproteins with lectins is limited by interference due to the
      competing oligosaccharides inherently present on antibodies. To prepare capture
      antibodies with significantly reduced binding of any lectin, the glycosylated
      protein domains (F(c)) of two anti-human chorionic gonadotropin antibodies were
      proteolytically removed. Depending on the individual antibody, usable fragments
      were generated either directly or effectively separated after cleavage through
      partial reduction and thiol coupling to an appropriate matrix. Importantly,
      neither method required additional purification of the antibody fragments before
      immobilization. Binding of a variety of lectins to the functional fragments was
      reduced by approximately 90% compared with intact immunoglobulin G in both an
      enzyme-linked immunosorbent assay and a biosensor format. These carbohydrate-free
      antibody fragments were used to bind the glycoprotein hormone, human chorionic
      gonadotropin, produced during normal pregnancy and that secreted by three human
      choriocarcinoma cell lines. Lectins bound to the unpurified gonadotropin
      glycoforms in distinct patterns consistent with glycan structures previously
      elucidated by others on hormone samples purified from the urine of pregnant women
      and of patients with choriocarcinoma. The methods described in this article are
      applicable for generating capture reagents universally suitable for lectin
      immunoassays of glycoproteins.

PMID- 15745746
TI  - Determination of meningococcal polysaccharides by capillary zone electrophoresis.
AB  - Meningococcal polysaccharides are medically important molecules and are the
      active components of vaccines against Neisseria meningiditis serogroups A, C,
      W135, and Y. This study demonstrates that free solution capillary zone
      electrophoresis (CZE) using simple phosphate/borate separation buffers is capable
      of separating intact, native polysaccharides from these four serogroups.
      Separation appeared to be robust with respect to variations in test conditions
      and behaved in expected ways with respect to changes in temperature, ionic
      strength, and addition of an organic modifier. Serogroups W135 and Y are composed
      of sialic acid residues alternating with either galactose or glucose,
      respectively. Separation of these serogroups could be achieved using phosphate
      buffer and was therefore not dependent on differential complexation with borate.
      Addition of sodium dodecyl sulfate to the separation buffer (i.e., MEKC) resulted
      in peak splitting for all four serogroups. Changes in polysaccharide size did not
      affect migration time for the size range examined, but serogroup C polysaccharide
      (a sialic acid homopolymer) was separable from sialic acid monosaccharide. CZE
      quantification of multiple lots of each of the four serogroups was compared to
      wet chemical determination by phosphorus or sialic acid measurement. Results from
      CZE determination showed good agreement with the wet chemical methods.

PMID- 15745747
TI  - Detection of myofibrillar proteins using a step gradient minigel with an
      ambiguous interface.
AB  - Myosin heavy chain (MHC), actin, titin, and nebulin are four major myofibrillar
      proteins that interact with each other. However, it is difficult to analyze the
      four proteins simultaneously on the same minigel due to their broad range of
      molecular weights. Numerous gradient gels are normally used to detect these
      myofibrillar proteins. The conventional step gradient gel provides better
      separation of the four major proteins, but several proteins accumulate at the
      interfaces between different gradient layers. To eliminate the obvious
      interfaces, we employed a plastic syringe filled with 12 and 4% acrylamide
      solutions simultaneously and then established an improved step gradient minigel
      with an ambiguous interface. It was determined by blue dextran in-gel
      visualization and scanning densitometry that the acrylamide concentration at the
      ambiguous interface gradually changed. Coomassie blue staining and immunoblotting
      revealed that the four proteins were successfully separated and transferred for
      analysis. This gel system is simple to prepare and easy to use, and it is a
      reliable method for analyzing myofibrillar proteins or other protein mixtures
      with broad molecular masses.

PMID- 15745748
TI  - Precise blood lead analysis using a combined internal standard and standard
      addition approach with disposable screen-printed electrodes.
AB  - We report here a highly accurate and efficient method for blood lead analysis
      (BLA) through the use of a disposable electrode. A new type of mercury-plated
      preanodized screen-printed carbon electrode, together with a thallium(III)
      internal standard, simplifies calibration and gives easily quantifiable signals
      for accurate BLA. A preanodization procedure improves the preconcentration
      ability of the working electrode through the effect of lead (Pb) complexing with
      an electrogenerated surface functional group, mainly >C=O. Under optimized
      conditions, the ratio of the anodic stripping peak currents of Pb and Tl (i.e.,
      i(Pb)/i(Tl)) is linear against [Pb] in the window of 1-300 ppb with a correlation
      coefficient and detection limit (signal-to-noise ratio=3) of 0.999 and 0.23 ppb,
      respectively. This approach was used to analyze blood samples (n=55) from workers
      at a local battery factory. The results are consistent with those obtained from
      graphite furnace atomic absorption spectroscopy and confirm the applicability of
      the proposed method.

PMID- 15745749
TI  - Folate receptor expression in carcinomas and normal tissues determined by a
      quantitative radioligand binding assay.
AB  - The folate receptor (FR) is a valuable therapeutic target that is highly
      expressed on a variety of cancers. The current development of folate-targeted
      cancer therapies has created the need for quantitating functional FRs in clinical
      specimens. In this article, we report on the creation of a highly sensitive
      radioactive binding method for quantitatively measuring FR expression in frozen
      tissue homogenates. Expression was positive in approximately 89% of human ovarian
      carcinomas but was negligible in both mucinous ovarian carcinomas and normal
      ovary. Expression was also significant in carcinomas of the kidney, endometrium,
      lung, breast, bladder, and pancreas. Normal tissues from humans and six different
      laboratory species were also analyzed; surprisingly, some interspecies
      variability in FR expression (especially in kidney, spleen, and lung tissue) was
      found. Interestingly, normal human lung tissue displayed high expression levels,
      whereas expression in normal lung of the other species was negligible. However,
      considering that folate-drug conjugates fail to accumulate in the lungs of
      patients, the consequence of this finding was not considered to be of clinical
      concern. Overall, this new methodology is reliable for determining functional FR
      expression levels in tissues, and it could possibly be a useful clinical test to
      determine patient candidacy for FR-targeted therapeutics.

PMID- 15745750
TI  - Plasma storage at -80 degrees C does not protect matrix metalloproteinase-9 from
      degradation.
AB  - Recently, matrix metalloproteinase-9 (MMP-9) has been identified as a
      cardiovascular risk marker and is increasingly being determined in clinical
      studies. Among other matrix metalloproteinases, MMP-9 is known to be self
      activable, as the cleavage of the propeptide leads to the formation of an active
      enzyme. In such a case the issue of storage of biological samples such as plasmas
      is of outstanding importance, as an enzymatic activity, although minimal, may
      remain at common storage temperature, i.e., -80 degrees C. Since 2000 our
      institute has created a plasma library from patients presenting with acute
      myocardial infarction. Recently, the evaluation of the MMP-9 led to the surprise
      of finding a dramatically low level of detectable enzyme in the oldest plasma
      samples. By using zymography, enzyme-linked immunosorbent assay and Western
      blots, we evaluated new and old samples and found that MMP-9 degrades over time.
      After 2 years, the detectable total MMP-9 dropped by 65%, and the asymptotic
      profile of the curve reached a residual 1% level after 43 months. These results
      were confirmed by zymography and western blotting. TIMP-1, the natural inhibitor
      of MMP-9 and MMP-2, remained rather stable over time. The results suggest that
      human plasma MMP-9 levels should be determined as soon as possible after
      sampling.

PMID- 15745751
TI  - Development and validation of a plate technique for screening of microorganisms
      that produce volatile sulfur compounds.
AB  - Volatile sulfur compounds (VSCs) are of major importance for flavor development
      in foodstuffs such as cheeses. Such compounds originate from the amino acid l
      methionine, which can be degraded to methanethiol (MTL), a common precursor to a
      variety of other VSCs. A plate assay based on double-layer petri dishes
      containing 5,5'-dithio-bis-2-nitrobenzoic acid (DTNB), a chemical used for the
      estimation of free thiols, in the upper layer provides an easy and reliable
      detection method for thiol-producing, cheese-ripening microorganisms. MTL
      production was quantitated by measuring the yellow-orange color intensity
      resulting from reaction with DTNB. Using this method, 18 Geotrichum candidum
      strains isolated from cheeses were compared, and the color intensity was found to
      be correlated with the production of microbial VSCs as measured by gas
      chromatographic analysis.

PMID- 15745752
TI  - A colorimetric high-throughput beta-hematin inhibition screening assay for use in
      the search for antimalarial compounds.
AB  - Antimalarial drugs such as chloroquine are believed to act by inhibiting hemozoin
      formation in the food vacuole of the malaria parasite. We have developed a new
      assay for measuring and detecting inhibition of synthetic hemozoin (beta-hematin)
      formation. Aqueous pyridine (5% v/v, pH 7.5) forms a low-spin complex with
      hematin but not with beta-hematin. Its absorbance obeys Beer's law, making it
      useful for quantitating hematin concentration in hematin/beta-hematin mixtures,
      allowing compounds to be investigated for inhibition of beta-hematin formation.
      The assay is rapid (60 min incubation) and requires no centrifugation. The beta
      hematin inhibition data show good agreement with alternative assay methods
      reported by four laboratories. The assay was adapted for high-throughput
      colorimetric screening, allowing visual identification of beta-hematin
      inhibitors. In this mode, the assay successfully detected all 18 beta-hematin
      inhibitors in a set of 47 compounds tested, with no false positive results. The
      quantitative in vitro antimalarial activities of a set of 13 aminoquinolines and
      quinoline methanols were found to correlate significantly with beta-hematin
      inhibition values determined using the assay.

PMID- 15745753
TI  - Analysis of glycoprotein hormone receptor extracellular domain interactions using
      a solid-phase capture assay.
AB  - The receptors for the glycoprotein hormones are unique in having a large
      extracellular domain that is responsible for mediating ligand binding. We
      describe the characterization, validation, and application of a solid-phase
      radioligand binding assay that can be used to assess the interaction of peptides
      and small molecules at the extracellular domain (ECD) of the follicle-stimulating
      hormone receptor (FSHR). The assay utilizes a C-terminal tag on the FSHR-ECD,
      which is used to capture the ECD and position it in a sterically favorable
      orientation on a solid-phase platform. Competition experiments with the cognate
      ligand, FSH, indicated that the interaction at the FSHR-ECD using the solid-phase
      assay was comparable to the full-length receptor assayed using a standard
      filtration assay. The utility of the assay was evaluated by competing several
      peptides and a small molecule for both the full-length FSHR and the FSHR-ECD. The
      solid-phase capture format allowed for the establishment of an assay to
      specifically evaluate compounds that interact at the ECD or require the full
      length receptor, thereby facilitating structure-activity studies. This assay
      format should be applicable to the other receptors of this family.

PMID- 15745754
TI  - Proteolytic peptide patterns as indicators for fungal infections and nonfungal
      affections of human nails measured by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry.
AB  - The discrimination of onychomycoses from endogenous diseases showing
      macroscopically similar symptoms is difficult. Long-lasting but ineffective
      antifungal therapies using systemic medicaments with often severe adverse
      reactions may be the consequence. We introduce a novel mass spectrometric method
      for the discrimination of fungal infections and nonfungal affections. Horn
      samples from patients infected by Trichophyton rubrum, from patients with
      psoriasis affecting nails, and from healthy persons were investigated.
      Onychomycoses are basically associated with proteolytic attacks of the virulent
      fungi-secreting proteases partly hydrolyzing the horn material. Endogenous
      diseases lack these proteolytic activities, conserving intact structural
      proteins. Tryptical digestion of horn material produced cleavage peptides
      detectable by matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry. Mass spectra of horn material infected by T. rubrum were
      clearly different from those originating from healthy test persons and from
      patients with psoriasis. Two methods were successfully applied to quantify the
      differences between groups of samples. One is based on the Euclidean match
      factor, and the other is based on the identification of specific peptide peaks
      occurring exclusively within one group of persons. The Euclidean match factor
      distributions and the occurrence of specific peptide peaks allowed a clear
      differentiation of T. rubrum infections from psoriasis patients and healthy test
      persons. No differences were found between healthy test persons and psoriasis
      patients. The method is rapid and does not require any cultivation.

PMID- 15745755
TI  - An amperometric hydrogen peroxide sensor based on immobilization of hemoglobin in
      poly(o-aminophenol) film at iron-cobalt hexacyanoferrate-modified gold electrode.
AB  - A series of hybrid iron-cobalt hexacyanoferrate (FeCoHCF) films were
      electrodeposited on gold electrodes from solutions containing 6mM Fe(CN)(6)(3-)
      with different concentrations of Co(2+) and Fe(3+). FeCoHCF films deposited from
      solutions with different molar ratios of iron were studied by cyclic voltammetry,
      and their solid states were characterized by Fourier transform infrared
      spectroscopy. The kind of FeCoHCF film that deposited from a solution with a
      molar ratio of iron of 0.4 showed the largest response current to H(2)O(2) and
      was characterized by energy-dispersive X-ray spectroscopy. Therefore, the
      optimized FeCoHCF film was combined with nonconducting poly(o-aminophenol) (POAP)
      film that entrapped the hemoglobin (Hb) to construct hydrogen peroxide biosensor.
      The response current of the Hb/POAP/FeCoHCF/Au electrode (29.8 nA) was nearly 40
      and was 1.5 times that of the Hb/POAP/Au (0.7 nA) and POAP/FeCoHCF/Au (20 nA)
      electrodes, respectively. The Michaelis-Menten constant of Hb in the
      Hb/POAP/FeCoHCF/Au film was 9.31 mM. These results show that the immobilized Hb
      in the Hb/POAP/FeCoHCF/Au film exhibits higher catalytic activity and larger
      response current to H(2)O(2) by the mediation of FeCoHCF. In addition, effects of
      applied potential, solution pH, and electroactive interferent on the response
      current of the Hb/POAP/FeCoHCF/Au electrode were investigated in detail.

PMID- 15745756
TI  - Advantages of sodium perchlorate solution as mobile phase for purification of
      synthetic oligonucleotides by anion exchange chromatography.

PMID- 15745758
TI  - A new method for the liquid chromatography analysis of methylated arginines in
      biological fluids and tissues by o-phthaldialdehyde postcolumn derivatization.

PMID- 15745757
TI  - Direct assessment of angiotensin-converting enzyme activity on the surface of
      human skin fibroblasts in culture.

PMID- 15745759
TI  - A method for functional mouse MDR3 P-glycoprotein reconstitution in Escherichia
      coli lipids.

PMID- 15745760
TI  - Pharmaceutical companies and ophthalmic research.

PMID- 15745761
TI  - Results of the European Glaucoma Prevention Study.
AB  - OBJECTIVE: The European Glaucoma Prevention Study (EGPS) seeks to evaluate the
      efficacy of reduction of intraocular pressure (IOP) by dorzolamide in preventing
      or delaying primary open-angle glaucoma (POAG) in patients affected by ocular
      hypertension (OHT). DESIGN: Randomized, double-masked, controlled clinical trial.
      PARTICIPANTS: One thousand eighty-one patients (age, > or =30 years) were
      enrolled by 18 European centers. The patients fulfilled a series of inclusion
      criteria, including: IOP 22 to 29 mmHg; 2 normal and reliable visual fields (on
      the basis of mean deviation and corrected pattern standard deviation or corrected
      loss variance of standard 30/II Humphrey or Octopus perimetry); normal optic disc
      as determined by the Optic Disc Reading Center. INTERVENTION: Patients were
      randomized to treatment with dorzolamide or placebo (the vehicle of dorzolamide).
      MAIN OUTCOME MEASURES: Efficacy end points were visual field, optic disc changes,
      or both. A visual field change during follow-up had to be confirmed by 2 further
      positive tests. Optic disc change was defined on the basis of the agreement of 2
      of 3 independent observers evaluating optic disc stereo slides. The safety end
      point was an IOP of more than 35 mmHg on 2 consecutive examinations. RESULTS:
      During the course of the study, the mean percent reduction in IOP in the
      dorzolamide group was 15% after 6 months and 22% after 5 years. Mean IOP declined
      by 9% after 6 months and by 19% after 5 years in the placebo group. At 60 months,
      the cumulative probability of converting to an efficacy end point was 13.4% in
      the dorzolamide group and 14.1% in the placebo group (hazard ratio, 0.86; 95%
      confidence interval [CI], 0.58-1.26; P = 0.45). The cumulative probability of
      developing an efficacy or a safety end point was 13.7% in the dorzolamide group
      and 16.4% in the placebo group (hazard ratio, 0.73; 95% CI, 0.51-1.06; P = 0.1).
      CONCLUSIONS: Dorzolamide reduced IOP by 15% to 22% throughout the 5 years of the
      trial. However, the EGPS failed to detect a statistically significant difference
      between medical therapy and placebo in reducing the incidence of POAG among a
      large population of OHT patients at moderate risk for developing POAG, because
      placebo also significantly and consistently lowered IOP.

PMID- 15745762
TI  - The Low-pressure Glaucoma Treatment Study (LoGTS) study design and baseline
      characteristics of enrolled patients.
AB  - OBJECTIVE: The Low-Pressure Glaucoma Treatment Study (LoGTS) seeks to evaluate
      visual field stability in low-pressure glaucoma patients randomized to
      intraocular pressure reduction in both eyes with topical twice daily brimonidine
      tartrate 0.2% versus twice daily timolol maleate 0.5%. This article describes the
      LoGTS design and presents baseline characteristics of the subjects. DESIGN:
      Randomized, multicenter, double-masked clinical trial. PARTICIPANTS: Low-pressure
      glaucoma patients 30 years of age or older were identified. Exclusion criteria
      included an untreated pressure of more than 21 mmHg, advanced visual field loss,
      and contraindications to study medications. INTERVENTIONS: Randomization of both
      eyes to double-masked monotherapy with brimonidine or timolol. Follow-up visits
      included Humphrey 24-2 full-threshold perimetry, tonometry every 4 months, and
      annual optic disc photography. MAIN OUTCOME MEASURE: Progression of visual field
      loss. RESULTS: One hundred ninety patients were randomized between 1998 and 2000.
      Mean age (+/-standard deviation) was 64.9+/-10.7 years. Women comprised 59.5% of
      the patients. Fifty-three patients (27.9%) had unilateral field loss. The 137
      patients with bilateral field loss were older than those with unilateral field
      loss: 65.7 versus 62.3 years of age (P<0.05). Mean untreated diurnal intraocular
      pressures were similar between the eyes of the bilateral patients (mean, 15.5
      mmHg in both eyes) and unilateral patients (mean, 16.0 mmHg in field loss vs.
      15.6 mmHg in fellow eyes). Visual field mean deviation for all eyes was -5.4+/
      4.7 decibels. Central corneal thickness in 168 phakic patients was 543 +/- 35
      microm (range, 435-655 microm); thickness was less than 500 microm in 15 eyes and
      was more than 600 microm in 11 eyes. Mean vertical cup-to-disc ratio for all eyes
      was 0.67+/-0.15. Unilateral field loss patients had a larger cup-to-disc ratio in
      the field loss eye (0.75+/-0.12) than the fellow eye with a normal field (0.60+/
      0.17, P<0.0001). Disc hemorrhage was present at baseline in 29 patients (32
      eyes). CONCLUSIONS: The LoGTS was successfully able to recruit and enroll
      patients with open-angle glaucoma and statistically normal intraocular pressure
      into a longitudinal, prospective clinical trial comparing 2 different glaucoma
      medications. Baseline characteristics of note were a preponderance of females,
      unilateral field loss in 27.9% of participants, and frequent optic disc
      hemorrhage. Central corneal thickness had a normal distribution and did not
      account for false low-pressure measurements in LoGTS patients.

PMID- 15745763
TI  - Risk of glaucoma in ocular hypertension with and without pseudoexfoliation.
AB  - PURPOSE: To compare glaucoma conversion rates in patients with ocular
      hypertension (OH) with and without pseudoexfoliation. DESIGN: Cohort study, based
      on 32,918 screening participants. PARTICIPANTS AND CONTROLS: Ninety-eight
      patients with OH and pseudoexfoliation and 98 matched controls. MAIN OUTCOME
      MEASURE: Perimetric glaucoma conversion. METHODS: A population-based glaucoma
      screening of elderly citizens of Malmo, Sweden, was conducted between 1992 and
      1997 to recruit participants for the Early Manifest Glaucoma Trial. Screening
      participants with intraocular pressure (IOP) between 24 and 32 mmHg and
      pseudoexfoliation were compared to controls among other screening participants
      without pseudoexfoliation but matched for baseline IOP, age, and gender, and the
      2 groups were invited to a reexamination. Computerized visual field tests were
      performed to identify persons with manifest glaucoma. Visual acuity, refraction,
      IOP, and central corneal thickness were also measured. RESULTS: After a mean of
      8.7 years (range: 6.3-11.4), 54 of 98 patients (55.1%) with pseudoexfoliation at
      the baseline examination and 27 of 98 patients (27.6%) without pseudoexfoliation
      had developed glaucoma. The risk ratio was 2.0 (P<0.0001). CONCLUSION: The
      glaucoma conversion rate was twice as high in patients with OH and
      pseudoexfoliation as in control patients matched for IOP, age, and gender. Thus,
      pseudoexfoliation was a strong independent risk factor for glaucoma in patients
      with OH.

PMID- 15745764
TI  - Comparison of macular and peripapillary measurements for the detection of
      glaucoma: an optical coherence tomography study.
AB  - OBJECTIVE: To evaluate macular nerve fiber layer (NFL) thickness in glaucomatous
      damage by optical coherence tomography (OCT) and to compare its discriminating
      power for glaucoma and glaucoma suspects with that of total macular thickness and
      peripapillary NFL thickness. DESIGN: Cross-sectional, case-control, comparative
      study. PARTICIPANTS: A total of 133 eyes from 133 subjects including 46 normal
      eyes, 48 glaucoma-suspect eyes, and 39 glaucoma eyes were enrolled. METHODS:
      Macular NFL thickness, total macular thickness, and peripapillary NFL thickness
      were measured by Stratus OCT in each diagnostic group. MAIN OUTCOME MEASURES: The
      patterns and measurements of macular NFL, total macular, and peripapillary NFL
      thickness in total mean, 4 quadrants, and 12 clock hours. The discriminating
      power of each parameter for detection of glaucoma suspects and glaucoma was
      evaluated by areas under the receiver operating characteristic curve (AROC).
      Correspondence with visual field function was studied by linear regression
      analysis. RESULTS: The macular NFL profile exhibited a double-hump pattern with
      peaks over superonasal and inferonasal sectors. A significant difference in
      macular NFL thickness between normal and glaucoma-suspect groups was found at the
      6-o'clock position, whereas a difference was found in all except the temporal
      clock hours between normal and glaucoma subjects. No significant difference in
      AROCs for detection of glaucoma suspects or glaucoma was found when macular NFL
      thickness and total macular thickness measurements were compared. However, mean
      macular NFL thickness demonstrated a stronger correlation with visual function
      than mean macular thickness (r = 0.39/R2 = 0.15 vs. r = 0.23/R2 = 0.05, P
      =0.042). Among all the findings, inferior peripapillary NFL thickness had the
      best performance in discriminating glaucoma (AROC, 0.91) and glaucoma suspects
      (AROC, 0.67). It also had the strongest correlation with visual function (r =
      0.60/R2 = 0.36, P<0.001). CONCLUSIONS: Macular NFL thickness was significantly
      reduced in glaucoma. It had a similar discriminating power for glaucoma detection
      but a stronger correlation with visual function than total macular thickness.
      Peripapillary NFL thickness, however, outperformed both total macular and macular
      NFL thickness in terms of glaucoma detection and visual function correlation.
      Peripapillary NFL thickness, as a total measurement of both macular and
      peripheral NFL, is still the best surrogate marker in glaucoma assessment.

PMID- 15745765
TI  - Visual field testing in glaucoma Medicare beneficiaries before surgery.
AB  - OBJECTIVE: The standard of care for progressive glaucoma that requires medical or
      surgical intervention includes visual field (VF) testing at least annually. This
      study aims to assess how commonly ophthalmologists perform VF testing before
      planned glaucoma surgery in the Medicare population, and whether variations in
      conformance occur across demographic and clinical subgroups. DESIGN:
      Retrospective, observational, population-based analysis. PARTICIPANTS: Thirteen
      thousand seven hundred fifty-three Medicare beneficiaries. METHODS: Data were
      obtained from a 5% random sample of Medicare beneficiaries undergoing glaucoma
      surgery in the United States from 1995 to 1999. The proportion of patients with
      evidence of at least 1 VF examination in the year before glaucoma surgery was
      determined. MAIN OUTCOME MEASURE: Rate of VF testing in the year before glaucoma
      surgery. RESULTS: Overall, 70% of patients had at least 1 VF test in the year
      preceding glaucoma surgery. This rate was significantly lower (P<0.001) in
      patients > or =85 years (56%), blacks (64%), patients with race other than white
      or black (66%), patients with diabetic retinopathy (60%), and patients with
      bilateral blindness (47%). CONCLUSIONS: The use of VF testing before surgery in
      glaucoma Medicare beneficiaries is suboptimal relative to the recommended
      standard of care. Underutilization is of particular concern in blacks, who are at
      increased risk of glaucomatous damage. Quality-of-care initiatives are needed to
      facilitate appropriate preoperative evaluations of glaucoma Medicare
      beneficiaries for glaucoma surgery.

PMID- 15745766
TI  - Prevalence of appositional angle closure determined by ultrasonic biomicroscopy
      in eyes with shallow anterior chambers.
AB  - PURPOSE: To determine the prevalence of appositional angle closure in eyes with a
      shallow peripheral anterior chamber but no peripheral anterior synechia (PAS) in
      Japanese patients. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty eyes of 80
      consecutive patients with a shallow peripheral anterior chamber, determined using
      the method of van Herick, and no PAS. METHODS: The anterior chamber angle was
      classified according to Shaffer's grading with noncompression gonioscopy
      superiorly, inferiorly, temporally, and nasally. The absence of PAS was confirmed
      by compression gonioscopy if necessary. The presence of appositional angle
      closure and the trabecular-iris angle (T-I angle) was determined with ultrasound
      biomicroscopy in each quadrant under light and dark conditions. Factors related
      to appositional angle closure were studied using logistic analysis, and the
      covariates included gender, age, refraction, gonioscopic grading, and the
      quadrant of the angle measured. MAIN OUTCOME MEASURES: Gonioscopic grading of the
      angle width, the T-I angle, and the prevalence of appositional closure. RESULTS:
      The gonioscopic grading (P<0.001 in light and dark) and the T-I angle (P<0.001 in
      light and dark) varied significantly among the 4 quadrants. Narrower angle
      gradings were observed more frequently superiorly. The T-I angle was narrower
      superiorly (in light) and inferiorly (in dark) (P<0.001 and P = 0.040,
      respectively). The T-I angle was significantly narrower in dark than in light
      (P<0.001). The sites with the narrower gonioscopic gradings tended to have a
      smaller T-I angle (P<0.001 and P = 0.006 in light and dark, respectively).
      Appositional angle closure was found in at least 1 quadrant in 46 (57.5%) of 80
      eyes in light and in 68 eyes (85%) in dark. Logistic analysis showed that
      gonioscopic grading and the quadrant were significantly related to the presence
      of appositional angle closure in light and dark (P<0.003 for both comparisons).
      CONCLUSIONS: Appositional angle closure was frequently observed in eyes with a
      shallow peripheral anterior chamber, especially under dark conditions in Japanese
      patients. The angle width, evaluated with conventional gonioscopic grading, and
      the quadrant of the angle were significantly related to the presence of
      appositional angle closure.

PMID- 15745767
TI  - Uveal effusion in primary angle-closure glaucoma.
AB  - PURPOSE: To determine the prevalence of uveal effusion in acute and chronic
      primary angle-closure glaucoma (PACG) or primary angle closure (PAC) and to
      compare it with the prevalence in eyes with open-angle glaucoma (OAG) or ocular
      hypertension. DESIGN: Prospective consecutive case series. PARTICIPANTS: Five
      hundred one eyes of 351 consecutive patients with PAC and 156 eyes of 116
      randomly selected primary OAG or ocular hypertension patients. The PAC group
      included 40 eyes of 35 patients with acute PACG and 30 unaffected fellow eyes, 39
      eyes and 35 fellow eyes with a history of acute PACG, and 357 eyes with chronic
      PAC. METHODS: Ultrasound biomicroscopic examination was performed to diagnose
      uveal effusion and to measure anterior chamber depth (ACD). MAIN OUTCOME
      MEASURES: Presence of uveal effusion and ACD. RESULTS: Uveal effusion was
      demonstrated in 23 eyes (58%) with acute PACG and 7 fellow eys (23%) (chi2 =
      8.17, P = 0.0043). Among eyes with chronic PAC, uveal effusion was present in 69
      [corrected](14%[corrected]), a higher prevalence than was found in open-angle
      patients (2 eyes [1.3%]) (chi2 = 19.3, P<0.001). In the chronic PAC group, the
      ACD of phakic eyes with uveal effusion (1.92+/-0.42 mm) was significantly
      shallower than that of phakic eyes without effusion (2.06+/-0.32 mm) (P = 0.019).
      CONCLUSIONS: Uveal effusion diagnosed by ultrasound biomicroscopy is a special
      feature in PAC, and is prevalent in acute PACG. Uveal effusion in phakic eyes
      with PAC is associated with shallowing of ACD.

PMID- 15745768
TI  - Visual acuity measurements using Fourier series harmonic analysis of
      videokeratography data in eyes after penetrating keratoplasty.
AB  - PURPOSE: Fourier harmonic analysis can decompose videokeratography data into
      spherical power, regular astigmatism, and irregular astigmatism (asymmetry and
      higher-order irregularity). The aim of this study was to evaluate whether
      determination of cylinder power by Fourier analysis facilitates measurements of
      visual acuity and refraction in eyes after penetrating keratoplasty. DESIGN:
      Cross-sectional study. PARTICIPANTS: Sixty-six eyes of 56 subjects who had
      undergone penetrating keratoplasty. METHODS: Spectacle-corrected visual acuity
      was measured in 2 ways: by the conventional and the Fourier methods. In the
      conventional method, the refraction was determined subjectively by reference to
      the measurement results of the autokeratometer and autorefractometer. In the
      Fourier method, the magnitude and axis of regular astigmatism were calculated by
      Fourier analysis of the videokeratography data, and spherical lenses were
      adjusted until best spectacle-corrected visual acuity was attained. MAIN OUTCOME
      MEASURES: Logarithm of the minimum angle of resolution (logMAR) visual acuity and
      refraction used for correction. RESULTS: The spectacle-corrected visual acuity
      obtained with the Fourier method (logMAR, 0.23+/-0.32; Snellen equivalent, 20/34)
      was significantly better than that attained with the conventional method (logMAR,
      0.31+/-0.29; Snellen equivalent, 20/41; P<0.001, paired t test). The cylinder
      power used for spectacle-corrected visual acuity measurements was significantly
      lower with the Fourier method (-2.41+/-1.26 diopters [D]) than with the
      conventional method (-3.53+/-1.64 D; P<0.001). The spherical equivalent at the
      final refraction was not different between groups (P = 0.207). CONCLUSIONS:
      Fourier analysis of videokeratography data significantly facilitates
      determination of refraction and measurement of best spectacle-corrected visual
      acuity in eyes with corneal irregular astigmatism, such as eyes that have
      undergone penetrating keratoplasty.

PMID- 15745769
TI  - Compressive C-shaped lamellar keratoplasty: a surgical alternative for the
      management of severe astigmatism from peripheral corneal degeneration.
AB  - OBJECTIVE: To describe a compressive lamellar surgical technique for treating
      severe astigmatism in peripheral corneal ectasia. DESIGN: Retrospective,
      noncomparative, interventional case series. PARTICIPANTS: Four eyes of 3 patients
      with either pellucid or Terrien's marginal corneal degeneration were included in
      this series. METHODS: C-shaped lamellar keratoplasty using multiple trephines of
      different sizes, with deliberate undersizing of the donor graft for a controlled
      compressive effect, was performed on these patients. MAIN OUTCOME MEASURES:
      Visual acuity outcome and refraction were measured at different intervals at up
      to 40 months of follow-up. RESULTS: All eyes achieved Snellen visual acuity of
      20/40 or better and stable astigmatism ranging from 0 to -2.75 diopter cylinder
      within 6 months, with no recurrence of corneal thinning or peripheral corneal
      vascularization. CONCLUSIONS: Compressive C-shaped lamellar keratoplasty is able
      to reduce severe corneal astigmatism in peripheral corneal ectasia and can result
      in good visual and refractive outcomes with early visual rehabilitation.

PMID- 15745770
TI  - An evaluation of image quality and accuracy of eye bank measurement of donor
      cornea endothelial cell density in the Specular Microscopy Ancillary Study.
AB  - PURPOSE: The Specular Microscopy Ancillary Study was designed to examine donor
      corneal endothelial specular image quality, compare the central endothelial cell
      density determined by eye banks with the endothelial cell density determined by a
      central specular microscopy reading center, and evaluate donor factors that may
      have an impact on specular image quality and endothelial cell density accuracy.
      DESIGN: Nonrandomized comparative trial. PARTICIPANTS: Endothelial specular
      images of donor corneas assigned in the Cornea Donor Study. METHODS: Certified
      readers assessed donor image quality (analyzable from fair to excellent vs.
      unanalyzable) and determined the central endothelial cell density. Independent
      adjudication was performed if there was a difference in the quality of grading or
      if the endothelial cell density varied by > or =5.0% between readers. Average
      reading center-determined endothelial cell density was compared with the
      endothelial cell density determined by each eye bank. MAIN OUTCOME MEASURES:
      Evaluation of image quality and accuracy of endothelial cell density. RESULTS: Of
      688 donor endothelial images submitted by 23 eye banks, 663 (96%) were analyzable
      (excellent, 40 [6%]; good, 302 [44%]; fair, 321 [47%]), and 25 (4%) were
      unanalyzable by reading center standards. In situ retrieval and greater
      epithelial exposure correlated with a higher image quality grading. The eye bank
      determined endothelial cell density of 434 of the 663 (65%) analyzable images
      were within 10% of the endothelial cell density determined by the reading center,
      whereas 185 (28%) were more than 10% higher and 44 (7%) were more than 10% lower.
      Greater variation in endothelial cell density between the eye banks and the
      reading center was observed with shorter time of death to preservation, presence
      of an epithelial defect, folds in Descemet's membrane, lower image quality, and
      the use of fixed-frame or center method endothelial cell density analysis.
      CONCLUSIONS: Overall, donor endothelial specular image quality and accuracy of
      endothelial cell density determination were good. However, the data suggest that
      factors that may affect image quality and contribute to variation in
      interpretation of the endothelial cell density should be addressed, because the
      donor endothelial cell density is an important parameter for assessing long-term
      corneal graft survival.

PMID- 15745771
TI  - Cataract surgery in patients with Fuchs' corneal dystrophy: expanding
      recommendations for cataract surgery without simultaneous keratoplasty.
AB  - OBJECTIVE: To evaluate the use of preoperative pachymetry in patients with Fuchs'
      dystrophy who are undergoing cataract extraction to predict the need for future
      penetrating keratoplasty and to compare these findings with current published
      recommendations. DESIGN: Retrospective noncomparative case series. PARTICIPANTS:
      A series of patients with Fuchs' dystrophy (136 eyes) undergoing cataract
      surgery. METHODS: We reviewed the medical records of 136 patients with Fuchs'
      dystrophy who underwent phacoemulsification and intraocular lens implantation
      between October 1990 and May 2002. MAIN OUTCOME MEASURES: Preoperative and
      postoperative visual acuity, pachymetry, and postoperative corneal decompensation
      requiring penetrating keratoplasty. RESULTS: The average preoperative corneal
      thickness was 584+/-39.5 microm (range, 482-674 microm). Fifty eyes (36.8%) had
      preoperative corneal thickness of > or =600 microm. The average postoperative
      best-corrected visual acuity (BCVA) was 20/33 (range, 20/15-20/250). Of the 50
      eyes with preoperative pachymetry measurements of > or =600 microm, 5 (10%)
      progressed to penetrating keratoplasty; 90% of the 50 eyes did not need corneal
      transplants within the first year after cataract surgery and had an average
      postoperative BCVA of 20/35 (range, 20/20-20/200). Of those with a corneal
      thickness of > or =640 microm, 83% did not need a corneal transplant within this
      same time period and had an average postoperative BCVA of 20/50 (range, 20/20
      20/200). CONCLUSIONS: To avoid unnecessary cost and delay in visual
      rehabilitation, we suggest changing the current recommendations for an initial
      triple procedure for eyes with preoperative pachymetry measurements of >600
      microm. Our data suggest that current cataract removal techniques allow for
      excellent visual rehabilitation in patients with Fuchs' dystrophy who have a
      preoperative corneal thickness of >600 microm, and we suggest that preoperative
      pachymetry measurements of >640 microm may be a better guideline. This
      recommendation can be further expanded above 640 mum if a visual acuity of less
      than 20/20 is acceptable. A prospective randomized controlled study is required
      for validation of this analysis.

PMID- 15745772
TI  - Surface calcification of a 3-piece silicone intraocular lens in a patient with
      asteroid hyalosis: a clinicopathologic case report.
AB  - OBJECTIVE: To illustrate the laboratory findings in a patient with bilateral
      asteroid hyalosis who presented with calcified deposits on a 3-piece silicone
      intraocular lens (IOL). DESIGN: Observational case report. METHODS: A 76-year-old
      diabetic woman underwent uneventful cataract surgery in 1994 with implantation of
      a silicone-optic polypropylene-haptic IOL in the left eye. A neodymium:yttrium
      aluminum-garnet (Nd:YAG) laser posterior capsulotomy was performed 2 years after
      cataract surgery, but persistent whitish deposits were observed on the posterior
      optic surface of the lens. Over the next 3 years, the opacification increased in
      the region corresponding to the capsulotomy. The IOL was explanted/exchanged. The
      right eye had cataract surgery in 1995. The acrylic lens implanted in this eye
      developed no opacities after 6 years. MAIN OUTCOME MEASURES: Gross, microscopic,
      and surface analyses of the explanted IOL. RESULTS: Gross and light microscopic
      analyses revealed the presence of confluent crustlike deposits on the central
      area of the posterior optic surface, as well as Nd:YAG pits. Individual spherules
      exhibiting a Maltese-cross pattern under polarizing light were also observed.
      Energy dispersive x-ray spectroscopic analyses demonstrated the composition of
      the confluent deposits to be similar to hydroxyapatite. CONCLUSIONS: An
      association between asteroid hyalosis and dystrophic calcification of IOLs has
      been reported only with silicone plate haptic designs. The material opacifying
      the 3-piece silicone lens probably was derived from the asteroid bodies or from
      the process that results in this vitreous condition. Clinical evaluation of other
      pseudophakic patients with asteroid hyalosis will confirm if this phenomenon is
      restricted to silicone IOLs.

PMID- 15745773
TI  - Stimulus-driven versus pilocarpine-induced biometric changes in pseudophakic
      eyes.
AB  - PURPOSE: Most trials that study the lens movement of accommodative intraocular
      lens (IOLs) use pilocarpine to stimulate ciliary muscle contraction. The aim of
      this study is to assess in vivo whether a more physiologic, stimulus-driven
      accommodation is comparable to pilocarpine-induced IOL movement. DESIGN:
      Controlled patient- and examiner-masked clinical trial. PARTICIPANTS: The study
      population included 38 eyes with accommodative IOL implants (1CU) and a control
      group of 28 eyes with conventional open-loop IOLs. METHODS: A high-precision
      biometry technique, partial coherence interferometry, was used to measure IOL
      position. Anterior chamber depth was measured during physiologic (near point) and
      pharmacological (pilocarpine 2%) stimulation. In a subgroup of 14 1CU eyes, IOL
      position was determined repeatedly within 90 minutes after pilocarpine
      administration. A different subgroup was investigated as to the effect of
      cyclopentolate on IOL position. Best-corrected distance visual acuity (VA), best
      corrected near VA, and distance-corrected near VA (DCNVA) were assessed using
      logarithm of the minimum angle of resolution charts. MAIN OUTCOME MEASURES:
      Anterior chamber depth change under pilocarpine and near-point-driven
      accommodation. RESULTS: Near-point accommodation did not induce movement of
      either the accommodating 1CU or the control IOLs. Pilocarpine induced a 201+/
      0.137-mm anterior movement of the 1CU IOL (P<0.001), compared with no movement
      within the control IOL groups (P>0.05). There was no significant (P>0.05)
      difference in DCNVA between the accommodative and open-loop IOLs. No correlation
      between near point- or pilocarpine-stimulated IOL movement and DCNVA was found.
      Concerning the time course of movement after pilocarpine administration, most of
      the 1CU IOLs showed some movement 30 minutes after application. Cyclopentolate
      induced ciliary muscle relaxation caused a posterior IOL movement, as compared
      with the relaxed state, when focusing on a distant target. CONCLUSION:
      Pilocarpine-induced ciliary muscle contraction seems to overestimate IOL movement
      relative to a monocular near-driven stimulus. Therefore, concerning IOL movement,
      pilocarpine may act as a superstimulus and may not adequately simulate daily life
      performance of accommodative IOLs. However, it may be helpful to evaluate the
      maximum potential of an accommodating IOL.

PMID- 15745774
TI  - Interim results of the United States investigational device study of the Ophtec
      capsular tension ring.
AB  - PURPOSE: To evaluate the safety and efficacy of the Ophtec capsular tension ring
      (CTR) in providing capsular support during and/or after cataract extraction in
      cases of a weak or partially broken ciliary zonule. DESIGN: Phase III
      multicenter, nonrandomized, investigational device study. PARTICIPANTS: Twelve
      investigators at 9 sites enrolled 224 subjects and placed 255 CTRs. METHODS:
      Capsular tension rings were placed in patients who were found to have a weakened
      or partially broken ciliary zonule comprising <34% of the circumference of the
      lens capsule. Two CTR models were evaluated, with noncompressed diameters of 12
      mm and 13 mm. Patients were examined preoperatively, intraoperatively, and
      postoperatively at day 1 and months 1, 3, 6, and 12. MAIN OUTCOME MEASURES: Rate
      of successful stabilization of the capsular bag and intraocular lens (IOL)
      centration, complications, and adverse events. RESULTS: Interim results from this
      ongoing study indicate that immediately after surgery 98.8% of IOLs were centered
      and 1.2% of the IOLs implanted (3/251) were not centered. Subsequently, the
      prevalence of decentered IOLs was 1.7% (4/236) 3 months after surgery, 3.8%
      (8/211) 6 months after surgery, and 2.3% (4/172) 12 months after surgery. The
      primary complication was posterior capsular opacification, which is unlikely to
      be a complication of CTR insertion. Neodymium:yttrium-aluminum-garnet laser
      capsulotomies have been performed in 12.8% of eyes by 12 months (22/172).
      CONCLUSIONS: Ophtec CTR models 275 and 276 safely provided capsular support
      during and after cataract surgery in cases where the zonule was weak or partially
      broken.

PMID- 15745775
TI  - Penetration of topically applied gatifloxacin 0.3%, moxifloxacin 0.5%, and
      ciprofloxacin 0.3% into the aqueous humor.
AB  - PURPOSE: To investigate the aqueous penetration of 3 commercially available
      ophthalmic fluoroquinolones. DESIGN: Prospective, double-masked, clinical study.
      PARTICIPANTS: Fifty-two eyes of 52 patients. INTERVENTION: Fifty-two patients
      undergoing cataract surgery were given preoperative topical gatifloxacin 0.3%
      (Zymar), moxifloxacin 0.5% (Vigamox), or ciprofloxacin 0.3% (Ciloxan). The
      patients were instructed to use their antibiotic drops 4 times a day for 3 days
      before surgery. On the day of surgery, patients were given their assigned
      antibiotic every 15 minutes for 3 doses, 1 hour before their procedure. At the
      time of surgery, 0.1 ml of aqueous fluid was aspirated from the anterior chamber
      with an air cannula needle attached to a tuberculin syringe. The aspirate was
      immediately stored at -70 degrees C. MAIN OUTCOME MEASURE: Fluoroquinolone
      concentrations were determined by reverse-phase high-pressure liquid
      chromatography assay technique with ultraviolet detection at a wavelength of 275
      nm. RESULTS: Mean aqueous concentration of gatifloxacin in 16 eyes was 0.63
      microg/ml (standard deviation [SD], 0.30), moxifloxacin in 14 eyes was 1.31
      microg/ml (SD, 0.46), and the mean concentration of ciprofloxacin in 22 eyes was
      0.15 microg/ml (SD, 0.11). CONCLUSIONS: Both moxifloxacin (P<0.001) and
      gatifloxacin (P<0.005) penetrated the aqueous humor at significantly higher
      levels than ciprofloxacin. Moxifloxacin penetrated into the aqueous humor at
      significantly higher levels than gatifloxacin (P<0.05). The anterior chamber
      levels of moxifloxacin and gatifloxacin may be due to the difference in
      antibiotic concentration.

PMID- 15745776
TI  - Outcomes and DNA analysis of ex vivo expanded stem cell allograft for ocular
      surface reconstruction.
AB  - PURPOSE: To investigate the outcome of a new technique of ex vivo expanded stem
      cell allograft for limbal stem cell deficiency (LSCD), and to characterize the
      ocular surface genotype after surgery. DESIGN: Retrospective noncomparative case
      series. PARTICIPANTS: Ten eyes of 10 patients with profound LSCD arising from
      ectodermal dysplasia (3 eyes), Stevens-Johnson syndrome (3 eyes), chemical injury
      (2 eyes), thermal injury (1 eye), and rosacea blepharoconjunctivitis (1 eye).
      INTERVENTION: Allogeneic corneal limbal stem cells were cultured on plastic and
      transplanted to the recipient eye after removal of conjunctival pannus. Amniotic
      membrane was applied in a bandage capacity. The procedure was combined with other
      reconstructive surgery in 2 cases. Nine patients received systemic cyclosporin A
      immunosuppression, and the DNA genotype was investigated with surface impression
      cytology. MAIN OUTCOME MEASURES: Parameters of LSCD, including vascularization,
      conjunctivalization, inflammation, epithelial defect, photophobia, and pain.
      RESULTS: The mean follow-up period was 28 months (range, 12-50). Seven of 10 eyes
      (70%) had improved parameters of LSCD at final follow-up and were considered
      successes. Four (40%) had improved visual acuity, including 3 having had further
      procedures for visual rehabilitation. Three patients failed to improve-1 with a
      thermal burn and lid deformity, 1 with Stevens-Johnson syndrome and severe dry
      eye, and 1 with ectodermal dysplasia who developed an epithelial defect at 26
      months. DNA analysis of the first 7 cases showed no ex vivo donor stem cell DNA
      present beyond 9 months. CONCLUSIONS: Ex vivo expanded stem cell allograft is a
      useful technique for restoring the ocular surface in profound LSCD. The absence
      of donor DNA beyond 9 months suggests that ongoing immunosuppression may be
      unnecessary and raises questions regarding the origin of the host corneal
      epithelium.

PMID- 15745777
TI  - Effects of volcanic ash on ocular symptoms: results of a 10-year survey on
      schoolchildren.
AB  - OBJECTIVE: To study the effects of volcanic ash on the ocular symptoms of
      schoolchildren ages 6 to 15 residing near Mt. Sakurajima, an active volcano.
      DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: A total of 10,380
      children ages 6 to 15, 1175 in a high-exposure area and 9205 in a low-exposure
      area, were studied. METHODS: High- and low-exposure areas for volcanic ash were
      selected. All subjects in both areas were examined annually each September in the
      decade from 1994 to 2003. MAIN OUTCOME MEASURES: The frequency of positive ocular
      symptoms in years with and without active volcanic eruptions was compared. The
      association of ocular symptoms with volcanic ash dispersal was assessed with the
      Mantel-Haenszel test or chi-square test. RESULTS: Subjects in the high-exposure
      area showed ocular symptoms more often than those in the low-exposure area
      (P<0.0001). Years of active volcanic eruptions (volcanic ash of 5000 g/m2/year or
      more) were closely related to years with a high frequency of ocular symptoms in
      subjects in the high-exposure area (P<0.05) but related conversely in subjects in
      the low-exposure area (P<0.01). Major ocular symptoms were redness, discharge,
      foreign body sensation, and itching, all treated effectively with eyedrops.
      CONCLUSIONS: Ocular symptoms in subjects were strongly influenced by volcanic
      eruptions in the Mt. Sakurajima area, but direct influence was limited to those
      living in areas very near the volcano (i.e., 4 km from the volcano's crater).

PMID- 15745778
TI  - Heterogeneity of the genetic risk in age-related macular disease: a population
      based familial risk study.
AB  - OBJECTIVE: To assess the extent of heterogeneity of the genetic risk of age
      related macular disease (AMD) among families. DESIGN: Case-controlled population
      based familial aggregation study. PARTICIPANTS: Participants comprised 190 first
      degree relatives of 65 case probands and 347 relatives of 100 control probands.
      All probands had been identified from the baseline phase of the Rotterdam Study
      in The Netherlands. METHODS: A family score was computed for each family based on
      the presence and type of macular disease, the expected risk of disease, and the
      number, extent of kinship, and age of all family members. MAIN OUTCOME MEASURES:
      Presence and stage of AMD as diagnosed on fundus photographs, family score, and
      logistic regression coefficient. RESULTS: The family score of case families
      showed a peak of approximately 0 with a skewed tail (14% of families) of higher
      than expected risks of disease toward a maximum of 2.9. The family score of
      control families centered on 0, apart from 1 outlier. The risk of AMD increased
      significantly with higher family scores (beta = 1.34; P<0.001). CONCLUSIONS: The
      heterogeneity of genetic risk among AMD families is considerable, and the
      proportion of high-risk families is relatively small. The family score method is
      relevant for genetic counseling as well as for implementation in studies of
      genetic dissection of AMD.

PMID- 15745780
TI  - Correlation of optical coherence tomography findings with visual acuity and
      macular lesions in patients with X-linked retinoschisis.
AB  - PURPOSE: To evaluate and correlate findings obtained by optical coherence
      tomography (OCT) imaging with visual acuity (VA) and macular lesions in patients
      with X-linked retinoschisis (XLRS). DESIGN: Prospective comparative case series.
      PARTICIPANTS: Thirty-one patients with confirmed XLRS. METHODS: Best-corrected VA
      was determined using Early Treatment Diabetic Retinopathy Study charts, and a
      dilated funduscopic examination was performed on all patients. For all patients,
      the macula in each eye was OCT imaged. A correlation between VA, macular
      presentation, and OCT images was determined. MAIN OUTCOME MEASURES: Analysis of
      findings on OCT images, including foveal thickness and the area of macular cystic
      appearing lesions, and their correlation with VA. RESULTS: Twenty-five patients
      with funduscopically evident cystic-appearing macular lesions demonstrated
      cysticlike spaces on OCT images. No statistically significant correlation was
      observed between the macular area of the cysticlike spaces, foveal thickness, and
      VA. Three patients with no funduscopic or OCT evidence of foveal cysts
      demonstrated thinning of the fovea on OCT images and more extensive reduction of
      their VA. Retinal papillomacular bundle nerve fiber layer thickness on OCT images
      showed no significant difference between control and patient groups. CONCLUSIONS:
      In XLRS patients with cystic-appearing macular lesions, there was a lack of
      correlation between VA, foveal thickness, and cystic area. The anatomical
      appearance of smaller perifoveal cysts on OCT imaging was most consistent with
      their location being primarily within the inner nuclear layer of the retina. In
      older patients, macular cysts were no longer apparent clinically or by OCT
      imaging, and foveal thickness was reduced. The findings on OCT images are
      consistent with the hypothesis of a primary Muller cell defect in patients with
      XLRS.

PMID- 15745779
TI  - The use of cholesterol-lowering medications and age-related macular degeneration.
AB  - PURPOSE: To evaluate the association between cholesterol-lowering medications and
      age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS:
      The Atherosclerosis Risk in Communities study is a prospective, population-based,
      cohort study conducted in 4 communities across the United States. A total of
      15792 individuals aged 45 to 65 years were enrolled between 1987 and 1989; fundus
      photographs were added to the study protocol at the 6-year follow-up (1993-1995).
      Cases were subjects who were identified as having AMD after applying a standard
      definition to their fundus photographs; controls did not have AMD. METHODS: The
      use of cholesterol-lowering medications at any time during the study was
      determined and compared between cases and controls, adjusting for the potentially
      confounding effect of demographic, behavioral, and medical characteristics. MAIN
      OUTCOME MEASURES: Presence of AMD and the use of cholesterol-lowering
      medications. RESULTS: A total of 871 AMD cases and 11,717 controls were
      identified. Of the AMD cases, 11% made use of cholesterol-lowering medications,
      as compared with 12.3% of controls (odds ratio [OR], 0.89; 95% confidence
      interval [CI], 0.71-1.11). Adjusting for the confounding influence of age,
      gender, and race revealed a statistically significant relationship between AMD
      and use of cholesterol-lowering medications (OR, 0.79; 95% CI, 0.63-0.99).
      CONCLUSIONS: The results of this study add to the growing body of evidence that
      cholesterol-lowering medications may reduce the risk of developing AMD.
      Additional research is needed to document the mechanism responsible for this
      association. A clinical trial of the impact of statins on AMD deserves
      consideration.

PMID- 15745781
TI  - Zoonotic intravitreal Onchocerca in Hungary.
AB  - OBJECTIVE: To report the case of a 65-year-old male patient from western Hungary
      who presented with rapidly progressive peripheral visual field (VF) loss and the
      sensation of an actively moving object in his central VF. DESIGN: Interventional
      case report. METHOD/INTERVENTION: A live nematode was removed from the anterior
      vitreous cavity by pars plana vitrectomy. RESULTS: The worm was successfully
      removed surgically, and the patient had an uneventful recovery. The nematode was
      identified as an immature filaria, most likely a member of the genus Onchocerca.
      CONCLUSIONS: Only 3 previous reports exist of human infection of the eye caused
      by zoonotic Onchocerca, 2 involving the subconjunctiva and 1 the cornea. Although
      rare, zoonotic onchocercal infection of the eye must be considered a differential
      diagnostic entity even in temperate climates.

PMID- 15745782
TI  - Iris and anterior chamber angle neovascularization after iodine 125 brachytherapy
      for uveal melanoma.
AB  - PURPOSE: Iris neovascularization (INV) and anterior chamber angle
      neovascularization after radiotherapy for uveal melanoma may lead to neovascular
      glaucoma and enucleation. However, neovascularization of the anterior ocular
      segment may respond favorably to treatment with panretinal photocoagulation. The
      purpose of this study was to evaluate the frequency, interval to development, and
      predisposing factors of anterior ocular segment neovascularization following
      iodine 125 (I125) brachytherapy for uveal melanoma. DESIGN: Retrospective,
      interventional, consecutive case series. PARTICIPANTS: Sixty-five patients (65
      eyes), consecutively treated with I125 brachytherapy for uveal melanoma from 1995
      through 2000 and followed up after radiation therapy for 24 months or more.
      METHODS: Clinical findings and ultrasonography characteristics as well as
      treatment parameters were analyzed. MAIN OUTCOME MEASURES: The frequency of INV
      was determined and the interval to development of INV as well as the predisposing
      factors were analyzed statistically. RESULTS: In 15 of 65 eyes (23%), INV was
      detected after I125 brachytherapy at a mean +/- standard deviation of 26.66+/
      11.63 months (median, 24 months; range, 9-48 months). Risk factors displaying the
      stronger correlation with INV were greater maximal tumor height (P<0.01), greater
      tumor vascularity (P<0.01), and disinsertion of horizontal rectus muscles (P =
      0.01). CONCLUSIONS: After I125 brachytherapy for choroidal melanoma, INV
      developed in 23% of eyes and was correlated with larger tumor size, greater tumor
      vascularity, and disinsertion of a horizontal rectus muscle.

PMID- 15745783
TI  - Short-term tolerance of pulse methylprednisolone therapy in patients with
      diabetes mellitus.
AB  - PURPOSE: To assess the short-term tolerance of pulse methylprednisolone in
      patients with diabetes. DESIGN: Retrospective study in a national eye center.
      PARTICIPANTS: Eighty patients with type 2 diabetes, half of them also treated for
      hypertension, who received 3-day pulse methylprednisolone between January 1999
      and December 2002 for eye disorders and were monitored according to a written
      protocol. MAIN OUTCOME MEASURE: Potentially serious side effects, serial blood
      glucose measurements, and hypoglycemic interventions during pulse therapy.
      RESULTS: Each pulse induced about 10 hours later a mean 2-fold peak increase of
      blood glucose. According to a 14-mmol/l (250 mg/dl) threshold glucose level for
      intervention, rapid insulin was required in 27 of 27 (100%) and 24 of 53 (45%)
      patients with glycosylated hemoglobin levels higher than 8% and up to 8%,
      respectively. In the latter group, patients older than 70 years had a 3-fold
      increased risk of requiring insulin. Significant side effects were systolic
      and/or diastolic blood pressure elevation > or = 180/110 mmHg (n = 6), ketosis
      without acidosis (n = 5), silent myocardial ischemia (n = 1), and disorientation
      (n = 1). All side effects were transient or controlled successfully by medical
      intervention. No infectious complication occurred during the treatment period.
      CONCLUSIONS: Pulse methylprednisolone is globally well tolerated in diabetic
      patients, but requires strict blood glucose and clinical monitoring.

PMID- 15745784
TI  - Repair of exposed porous polyethylene implants utilizing flaps from the implant
      capsule.
AB  - PURPOSE: To determine the feasibility of the use of flaps from the capsule
      surrounding porous polyethylene implants in repairing large or recurrent implant
      exposures. DESIGN: Retrospective, noncomparative, interventional case series.
      PARTICIPANTS: Sixteen patients with exposed porous polyethylene implants.
      METHODS: Vertical and horizontal flaps were created from the implant capsule.
      These flaps were used to create a double layer of closure to seal the exposure.
      All patients had a minimum follow-up of at least 12 months. MAIN OUTCOME
      MEASURES: Repair of the exposure without recurrence during the follow-up
      interval, and assessment of complications. RESULTS: At the last follow-up visit,
      the socket was completely healed in all but 2 patients. In 1 of them, the implant
      was subsequently exchanged. Other complications included motility loss,
      conjunctival cyst, and granuloma formation. CONCLUSIONS: The use of the implant
      capsule to salvage exposed porous polyethylene implants is an effective
      technique; it is associated with some complications that can be minimized by
      careful case selection.

PMID- 15745786
TI  - Eyelid position measurement.

PMID- 15745788
TI  - PRK for myopic anisometropia.

PMID- 15745790
TI  - Tear function in babies.

PMID- 15745791
TI  - Birdshot chorioretinopathy.

PMID- 15745792
TI  - Sheathotomy to decompress BRVO.

PMID- 15745794
TI  - Design, synthesis, and biological activity of novel PPARgamma ligands based on
      rosiglitazone and 15d-PGJ2.
AB  - To develop novel PPARgamma ligands, we synthesized thirteen 3-{4-(2
      aminoethoxy)phenyl}propanoic acid derivatives, which are designed based on the
      structures of rosiglitazone and 15d-PGJ2. Among these compounds, compound 9 was
      found to be as potent as rosiglitazone in a binding assay and a preadipocyte
      differentiation test. Molecular modeling suggested that the nonyl group of 9
      interacted with hydrophobic amino acid residues constructing the hydrophobic
      region of PPARgamma protein where the alkyl chain of 15d-PGJ2 is expected to be
      located.

PMID- 15745795
TI  - Identification of small molecule inhibitors of the hepatitis C virus RNA
      dependent RNA polymerase from a pyrrolidine combinatorial mixture.
AB  - HTS of the compound collection for inhibition of the HCV RNA dependent RNA
      polymerase identified two 168 member N-acyl pyrrolidine combinatorial mixture
      hits. Deconvolution and expansion of these mixtures by solid phase synthesis to
      establish initial SAR and identify a potent inhibitor is reported.

PMID- 15745796
TI  - 3H-Quinazolin-4-ones as a new calcilytic template for the potential treatment of
      osteoporosis.
AB  - Structure-activity relationship studies, focused on identification of the active
      pharmacophore fragments in a single high-throughput screening calcilytic hit,
      resulted in the discovery of potent calcium receptor antagonists, substituted 3H
      quinazolin-4-ones.

PMID- 15745797
TI  - Novel cyclized Pifithrin-alpha p53 inactivators: synthesis and biological
      studies.
AB  - Starting from various cyclic or bicyclic ketones, we have synthesized novel
      Pifithrin-alpha analogues bearing different methyl substituted phenyl ketone
      groups at the N3-position of the 2-iminothiazole heterocycle. From stability
      studies in a biological medium as well as under specific chemical conditions, we
      have shown by NMR techniques that through a dehydration process, some derivatives
      can generate their corresponding cyclized analogues. All of the new analogues,
      Pifithrin-like and polycyclic dehydrated derivatives were assessed for their p53
      inactivation potency by measuring survival of cortical neurons, whose death was
      induced by the DNA-damaging agent etoposide. Pifithrin-alpha like 2f as well as
      the cyclic dehydrated 6b analogue were found to be one log more potent p53
      inactivators than reference compound Pft-alpha, with EC50 values ranging around
      30 nM. These results support the finding that p53 inactivation by Pft-alpha
      analogues could be also due to the presence of the cyclic dehydrated Pft-alpha
      forms, generated in situ in the biological assay incubation medium.

PMID- 15745798
TI  - Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 3:
      Identification and biological activity of indanone containing mGlu2 receptor
      potentiators.
AB  - We have identified and synthesized a series of phenyl-tetrazolyl and 4
      thiopyridyl indanones as allosteric potentiators of the metabotropic glutamate
      receptor 2. Structure activity relationship studies directed toward improving the
      potency and level of potentiation, as well as PK properties, led to the discovery
      of 28 (EC50=186 nM), which displayed activity in a rodent model for
      schizophrenia.

PMID- 15745799
TI  - Synthesis of isonicotinic acid N'-arylidene-N-[2-oxo-2-(4-aryl-piperazin-1-yl)
      ethyl]-hydrazides as antituberculosis agents.
AB  - A new series of antituberculosis agents 6-9 was designed, synthesized and
      evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv
      and clinical isolates in an agar dilution method. Compound 9h showed comparable
      in vitro activity (MIC) to isoniazid against M. tuberculosis H37Rv and clinical
      isolates (sensitive strains) and superior activity against resistant strains of
      M. tuberculosis.

PMID- 15745800
TI  - Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships
      of N-1-heteroalkyl-4-hydroxyquinolon-3-yl-benzothiadiazines.
AB  - N-1-Alkylamino and N-1-alkyloxy-4-hydroxyquinolon-3-yl benzothiadiazines were
      synthesized and evaluated as inhibitors of genotype 1 HCV polymerase. The N-1
      alkyloxy derivatives were not potent inhibitors, however N-1-alkylamino
      derivatives displayed comparable potency to carbon analogs. Analogs with
      aliphatic substituents were significantly more potent than those with benzylic
      substituents against genotype 1a polymerase. The most potent inhibitors contained
      small alkyl or carbocyclic substituents and exhibited IC50's of 50-100 and 200
      400 nM against genotype 1b and 1a HCV polymerase, respectively.

PMID- 15745801
TI  - Synthesis and in vitro biological evaluation of a carbon glycoside analogue of
      morphine-6-glucuronide.
AB  - Attachment of a glucose moiety to 6-beta-aminomorphine afforded compound 3, where
      the glucose moiety was linked to the C-6 nitrogen atom by a two-carbon bridge.
      The synthesis of 3 was accomplished in eight steps from 3-triisopropylsilyl-6
      beta-aminomorphine and 2,3,4,6-tetra-O-benzyl-D-glucose. The C-glycoside 3 was
      prepared with the objective of examining a metabolically stable analogue of
      morphine-6-glucuronide and determining the potency and selectivity of opioid
      receptor binding. Competition binding assays showed that 3 bound to the mu opioid
      receptor with a Ki value of 3.5 nM. The C-glycoside 3 exhibited delta/mu and
      kappa/mu selectivity ratios of 76 and 165, respectively. The synthetic
      intermediate (i.e., benzyl precursor, compound 11) bound to the mu opioid
      receptor with a Ki value of 0.5 nM, was less selective for the mu opioid
      receptor. The [35S]GTPgammaS assay was used to evaluate the functional properties
      of compounds 3 and 11. Compound 3 was determined to be a full agonist at the mu
      opioid receptor, whereas compound 11 was found to be a partial agonist. Compound
      3 was determined to be very stable in the presence of human liver S9, and rat and
      monkey liver microsomes: no detectable loss of 3 was observed up to 90 min.
      Compound 3 was also very stable at pH 2 and pH 7.4, suggesting that 3 possessed
      properties for sustained duration of action.

PMID- 15745802
TI  - Aminocyanopyridine inhibitors of mitogen activated protein kinase-activated
      protein kinase 2 (MK-2).
AB  - A class of inhibitors of mitogen-activated protein kinase-activated protein
      kinase 2 (MK-2) was discovered. These compounds have demonstrated activity
      against the enzyme with IC50 values as low as 130 nM and suppress the expression
      of TNFalpha in U937 cells. These represent the first small molecule inhibitors of
      MK-2 to be reported.

PMID- 15745803
TI  - Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents:
      parallel synthesis for lead optimization of amide region.
AB  - A novel series of p21 chemoselective agents containing a pyrazolo[1,5-a]pyrimidin
      7-yl phenyl amides were identified by high throughput screening. Optimization of
      the amide region by parallel synthesis and the iterative design toward
      understanding structure-activity relationship to improve potency are described.
      The isopropyl carbamate derivative 34 was identified as a highly chemoselective
      agent displaying a potency of 51 nM in the p21 deficient cell line.

PMID- 15745804
TI  - Cyclization-activated prodrugs. Synthesis, reactivity and toxicity of dipeptide
      esters of paracetamol.
AB  - Dipeptide esters of paracetamol were prepared in high yields. These compounds are
      quantitatively hydrolyzed to paracetamol and corresponding 2,5-diketopiperazines
      at pH 7.4 and 37 degrees C. The reactivity is increased in sarcosine and proline
      peptides and decreased by bulky side chains at both the N- and C-terminal
      residues of the dipeptide carrier. Moreover, dipeptide esters of paracetamol did
      not affect the levels of hepatic glutathione. Thus, dipeptides seem promising
      candidates as carriers for cyclization-activated prodrugs.

PMID- 15745805
TI  - Novel and potent NPY5 receptor antagonists derived from virtual screening and
      iterative parallel chemistry design.
AB  - In the quest for NPY5 receptor antagonists a virtual screening approach yielded a
      novel and potent hit class from a limited compound selection. The tight and
      seamless integration between virtual screening and rapid parallel chemistry
      within the framework of the Roche Lead Generation unit led in only two rounds of
      iterative chemistry optimisation to a much broader understanding of the factors
      which influence the potency of the thiazole hit class.

PMID- 15745806
TI  - Inositol tripyrophosphate: a new membrane permeant allosteric effector of
      haemoglobin.
AB  - Nine inositol tripyrophosphate (ITPP) salts have been synthesized. Their ability
      to act as allosteric effectors of haemoglobin (Hb) has been measured in vitro
      with free Hb and whole blood. All the synthesized compounds bound to free Hb and
      were also able to cross, to a certain extent, the plasma membrane of the red
      blood cells (RBCs) in whole blood samples, lowering the affinity of Hb for
      oxygen. The oxy-haemoglobin dissociation curves were significantly shifted
      towards higher values of oxygen partial pressures, both for free Hb and for
      intracellular Hb in whole blood.

PMID- 15745807
TI  - The stability of lipidic analogues of GnRH in plasma and kidney preparations: the
      stereoselective release of the parent peptide.
AB  - The conjugation of a lipoamino acid to the N-terminus of Gonadotropin releasing
      hormone (GnRH) produces a lipophilic peptide from which the parent GnRH peptide
      is released into solution on treatment with plasma and kidney enzyme preparation.
      Our findings show that one stereoisomer of the Laa is cleaved very rapidly,
      providing a bolus dose of the peptide while the opposite stereoisomer is cleaved
      much more slowly, providing prolonged elevation of peptide concentration. The Laa
      Glu linkage appears to act as a two phase prodrug system.

PMID- 15745808
TI  - iPF2alpha-III-17,18,19,20-d4: total synthesis and metabolism.
AB  - The first total synthesis of 17,18,19,20-d4-iPF2alpha-III 32, a deuterated analog
      of iPF2alpha-III, is described. We have used this analog in some beta-oxidation
      studies with rat liver homogenates and have shown that 32 was metabolized to
      17,18,19,20-tetradeutero-2,3-dinor-iPF2alpha-III 36 and 17,18,19,20-tetradeutero
      2,3-dinor-5,6-dihydro-iPF2alpha-III 37.

PMID- 15745809
TI  - Homotryptamines as potent and selective serotonin reuptake inhibitors (SSRIs).
AB  - A series of N,N-dimethylhomotryptamines was prepared and their binding affinities
      at the serotonin transporter (SERT) were determined. Compounds possessing an
      electron withdrawing substituent at the C5-position of the indole nucleus were
      found to be potent SSRIs. Initial attempts at conformational restriction of the
      propylamine sidechain by incorporation of a quinuclidine bicyclic structure did
      not improve binding affinity at SERT.

PMID- 15745810
TI  - Melanocortin subtype-4 receptor agonists containing a piperazine core with
      substituted aryl sulfonamides.
AB  - The biological activity for a set of melanocortin-4 receptor (MC4R) agonists
      containing a piperazine core with an ortho-substituted aryl sulfonamide is
      described. Compounds from this set had binding and functional activities at MC4R
      less than 30 nM. The most selective compound in this series was >25,000-fold more
      potent at MC4R than MC3R, and 490-fold more potent at MC4R than MC5R. This
      compound also reduced food intake after oral dosing at 25, 50, and 100 mg kg(-1)
      in fasted mice.

PMID- 15745811
TI  - Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors
      of osteoclast formation.
AB  - Two series of oleanolic acid derivatives were synthesized and their inhibitory
      activity on the formation of osteoclast-like multinucleated cells (OCLs) induced
      by 1alpha,25-dihydroxy vitamin D3 was evaluated in a co-culture assay system. The
      structure-activity relationships, together with electronic structure based on the
      frontier molecular orbitals, for example, HOMO and LUMO, related to different
      amino acid substituents were studied. Derivatives with proline or phenylalanine
      showed a tendency to enhance the inhibitory activity.

PMID- 15745812
TI  - 3-Arylidene-1-(4-nitrophenylmethylene)-3,4-dihydro-1H-naphthalen-2-ones and
      related compounds displaying selective toxicity and reversal of multidrug
      resistance in neoplastic cells.
AB  - The incorporation of the 1-aryl-5-(4-nitrophenyl)-3-oxo-1,4-pentadienyl group
      into 3,4-dihydro-1H-naphthalenyl, cyclohexyl, 2,3-dihydro-1H-indenyl and
      cyclopentyl scaffolds led to the discovery of various compounds with selective
      toxicity for malignant cells and ability to reverse multidrug resistance.

PMID- 15745813
TI  - 3-(2,5-Dihydro-1H-pyrrol-2-ylmethoxy)pyridines: synthesis and analgesic activity.
AB  - We disclose an efficient procedure for the preparation of ethers of 2-substituted
      2-hydroxymethylpyrroline and of 2-aminomethyl-3-pyrrolines, involving, as a key
      step, formation and nucleophilic ring opening of a cyclic sulfamidate. Several
      new analogs of epibatidine (1) and tebanicline (ABT-594, 2) were prepared and
      tested for analgesic activity in the mouse formalin model.

PMID- 15745814
TI  - Synthesis and SAR of diazepine and thiazepine TACE and MMP inhibitors.
AB  - Potent and selective TACE and MMP inhibitors utilizing the diazepine and
      thiazepine ring systems were synthesized and evaluated for biological activity in
      in vitro and in vivo models of TNF-alpha release. Oral activity in the mouse LPS
      model of TNF-alpha release was seen. Efficacy in the mouse collagen induced
      arthritis model was achieved with diazepine 20.

PMID- 15745815
TI  - Nonpeptide alpha(v)beta3 antagonists: identification of potent, chain-shortened 7
      oxo RGD mimetics.
AB  - Potent, novel 7-oxo alpha(v)beta3 antagonists have been prepared. These
      antagonists offer decreased plasma protein binding and excellent pharmacokinetic
      profiles.

PMID- 15745816
TI  - QSAR for anti-RNA-virus activity, synthesis, and assay of anti-RSV
      carbonucleosides given a unified representation of spectral moments, quadratic,
      and topologic indices.
AB  - The unified representation of spectral moments, classic topologic indices,
      quadratic indices, and stochastic molecular descriptors show that all these
      molecular descriptors lie within the same family. Consequently, the same prior
      probability for a successful quantitative-structure-activity-relationship (QSAR)
      may be expected irrespective of which indices are selected. Herein, we used
      stochastic spectral moments as molecular descriptors to seek a QSAR using a
      database of 221 bioactive compounds previously tested against diverse RNA-viruses
      and 402 nonactive ones. The QSAR model thus obtained correctly classifies 90.9%
      of compounds in training. The model also correctly classifies a total of 87.9% of
      207 compounds on additional external predicting series, 73 of them having anti
      RNA-virus activity and 134 nonactive ones. In addition, all compounds were
      regrouped into five different subsets for leave-group-out studies: (1) anti
      influenza, (2) anti-picornavirus, (3) anti-paramyxovirus, (4) anti-RSV/anti
      influenza, and (5) broad range anti-RNA-virus activity. The model has retained
      overall accuracies of about 90% on these studies validating model robustness.
      Finally, we exemplify the practical use of the model with the discovery of
      compounds 124 and 128. These compounds presented MIC50 values=3.2 and 8 microg/mL
      against respiratory syncytial virus (RSV) respectively. Both compounds also have
      low cytotoxicity expressed by their Minimal Cytotoxic Concentrations >400
      microg/mL for HeLa cells. The present approach represents an effort toward a
      formalization and application of molecular indices in bioorganic and medicinal
      chemistry.

PMID- 15745817
TI  - Combinatorial approaches towards the discovery of new tryptase inhibitors.
AB  - The synthesis and evaluation as tryptase inhibitors of a library of 2,5
      diketopiperazine derivatives containing guanidine or amidine functional groups is
      reported. Among the compounds evaluated, derivatives 6{CG4-CG8} and 6{CG4-CG9}
      are the most active compounds and have marked selectivity towards tryptase in
      front of trypsin.

PMID- 15745818
TI  - Synthesis and characterization of a carboranyl-tetrabenzoporphyrin.
AB  - An expeditious synthetic route to a carboranyl-substituted tetrabenzoporphyrin is
      reported. The absorption and emission spectra of water-soluble
      tetrabenzoporphyrin 4 are distinct from those of a known carboranylporphyrin (5).
      Both tetrabenzoporphyrin 4 and porphyrin 5 were found to be non-toxic toward V79
      hamster lung fibroblast cells at 300 microM, using an MTT assay. The X-ray
      structure of a Cu(II)-carboranyl-tetrabenzoporphyrin is presented and discussed.

PMID- 15745819
TI  - Potent and selective [2-imidazol-1-yl-2-(6-alkoxy-naphthalen-2-yl)-1-methyl
      ethyl]-dimethyl-amines as retinoic acid metabolic blocking agents (RAMBAs).
AB  - A series of [2-imidazol-1-yl-2-(6-alkoxy-naphthalen-2-yl)-1-methyl-ethyl]
      dimethyl-amines were designed and synthesized as CYP26 inhibitors, serving as
      retinoic acid metabolic blocking agents (RAMBA's).

PMID- 15745820
TI  - Estrogen receptor ligands. Part 10: Chromanes: old scaffolds for new SERAMs.
AB  - The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective
      ligands are described. X-ray studies revealed that the origin of the ER alpha
      selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl
      chromane platform. Selected compounds from this class demonstrated very potent in
      vivo antagonism of estradiol in an immature rat uterine weight assay, effectively
      inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm,
      and lowered serum cholesterol levels in ovx'd adult rat models. The best
      antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and
      were shown to be estrogen receptor down-regulators (SERDs).

PMID- 15745821
TI  - Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with
      organic phosphates and phosphonates.
AB  - The interaction of five human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, that
      is, hCA I, II, IV, V, and IX with a small library of phosphonic acids/organic
      phosphates, including methylphosphonic acid, MPA; phenylphosphonic acid, PPA; N
      (phosphonoacetyl)-L-aspartic acid, PALA, methylene diphosphonic acid MDPA, the O
      phosphates of serine (Ser-OP) and threonine (Thr-OP) as well as the antiviral
      phosphonate foscarnet has been studied. hCA I was activated by all these
      compounds, with the best activators being MPA and PPA (K(A)s of 0.10-1.20
      microM). MPA and PPA were on the other hand nanomolar inhibitors of hCA II (K(I)s
      of 98-99 nM). PALA showed an affinity of 7.8 microM, whereas the other compounds
      were weak, millimolar inhibitors of this isozyme. The best hCA IV inhibitors were
      PALA (79 nM) and PPA (5.4 microM), whereas the other compounds showed K(I)s in
      the range of 0.31-5.34 mM. The mitochondrial isozyme was weakly inhibited by all
      these compounds (K(I)s in the range of 0.09-41.7 mM), similarly to the
      transmembrane, tumor-associated isozyme (K(I)s in the range of 0.86-2.25 mM).
      Thus, phosphonates may lead to CA inhibitors with selectivity against two
      physiologically relevant isozymes, the cytosolic hCA II or the membrane-bound hCA
      IV.

PMID- 15745822
TI  - Discovery and SAR studies of a novel series of noncovalent cathepsin S
      inhibitors.
AB  - A novel series of competitive, reversible cathepsin S (CatS) inhibitors was
      discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety
      was found to be an effective replacement for the 4-arylpiperazin-1-yl group found
      in our earlier series of CatS inhibitors. This replacement imparted improved PK
      properties as well as decreased off-target activity. Optimization of the
      ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670,
      which represents a novel class of selective, noncovalent, reversible, and orally
      bioavailable inhibitors of cathepsin S.

PMID- 15745823
TI  - Design and synthesis of a potent macrocyclic 1,6-naphthyridine anti-human
      cytomegalovirus (HCMV) inhibitors.
AB  - A novel class of macrocyclic 1,6-napthyridines designed to adopt the presumed
      bioactive conformation of anti-HCMV acyclic 1,6-napthyridines are described. Both
      14- and 15-membered macrocycles were shown to be highly potent against HCMV HSV-1
      and HSV-2.

PMID- 15745824
TI  - Identification of a 5-HT4 receptor antagonist clinical candidate through side
      chain modification.
AB  - Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with
      propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher
      affinity analogs 4-6. In vitro drug metabolism screens and cassette
      pharmacokinetic studies in the dog led to identification of the N
      methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and
      safety parameters sufficient for advancement to the clinic for the treatment of
      urinary incontinence.

PMID- 15745825
TI  - Design, synthesis and structure-activity relationship studies of
      hexahydropyrazinoquinolines as a novel class of potent and selective dopamine
      receptor 3 (D3) ligands.
AB  - A hexahydropyrazinoquinoline (compound 5c) was previously discovered as a novel
      D3 ligand with a moderate binding affinity to the D3 receptor (Ki=304 nM) but no
      selectivity over the D1-like and D2-like receptors. In this study, we wish to
      report the design, synthesis and structure-activity relationship studies of a
      series of novel hexahydropyrazinoquinolines. Our efforts resulted in new
      compounds with improved binding affinity and selectivity. Among them, compound
      12d has a Ki value of 2.6 nM for its binding affinity to the D3 receptor and has
      >2000- and 99-fold selectivity over the D1-like and D2-like receptors,
      respectively, representing a potent and selective D3 ligand.

PMID- 15745827
TI  - Novel beta-(imidazol-4-yl)-beta-amino acids: solid-phase synthesis and study of
      their inhibitory activity against geranylgeranyl protein transferase type I.
AB  - Solid-phase synthesis of imidazolyl-beta-amino acid derivatives is described.
      Several analogs demonstrated moderate inhibition of geranylgeranyl protein
      transferase type I (GGPT I).

PMID- 15745826
TI  - 1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor
      ligands.
AB  - 4-Sulfonyl analogs of 1-(1-naphthyl)piperazine bind at human 5-HT6 receptors and
      represent a novel class of human 5-HT6 receptor ligands.

PMID- 15745828
TI  - From a total synthesis of cepabactin and its 3:1 ferric complex to the isolation
      of a 1:1:1 mixed complex between iron (III), cepabactin and pyochelin.
AB  - A novel and straightforward total synthesis of cepabactin and its iron (III)
      complex is described. The latter compound was compared and identified to that
      obtained from the cultures of Burkholderia cepacia. On treatment of the growth
      medium of two different strains of B. cepacia with ferric chloride, we have
      isolated and characterized an unexpected mixed complex of iron (III), cepabactin
      and pyochelin.

PMID- 15745829
TI  - Synthesis and fluorescence studies of thiazole orange tethered onto
      oligonucleotide: development of a self-contained DNA biosensor on a fiber optic
      surface.
AB  - Thiazole orange dyes were derivatized with ethylene glycol linkers of various
      lengths, and were covalently linked to the 5' end of the oligonucleotides after
      solid-phase synthesis. The labeled oligonucleotides exhibited enhanced
      fluorescence upon hybridization to complementary DNA sequences at the surfaces of
      optical fibers, providing for a self-contained labeling strategy. It was
      determined that the melt temperatures of DNA hybrids using one mixed
      polypyrimidine base oligonucleotide sequence were dependent on the length of the
      tethers, and that the melt temperature could be shifted by more than 10 degrees C
      when tethers were introduced.

PMID- 15745831
TI  - A two-state homology model of the hERG K+ channel: application to ligand binding.
AB  - Homology models based on available K+ channel structures have been used to
      construct a multiple state representation of the hERG cardiac K+ channel. These
      states are used to capture the flexibility of the channel. We show that this
      flexibility is essential in order to correctly model the binding affinity of a
      set of diverse ligands. Using this multiple state approach, a binding affinity
      model was constructed for set of known hERG channel binders. The predicted pIC50s
      are in good agreement with experiment (RMSD: 0.56 kcal/mol). In addition, these
      calculations provide structures for the bound ligands that are consistent with
      published mutation studies. These computed ligand bound complex structures can be
      used to guide synthesis of analogs with reduced hERG liability.

PMID- 15745830
TI  - A chromism-based assay (CHROBA) technique for in situ detection of protein kinase
      activity.
AB  - A unique chromism-based assay technique (CHROBA) using photochromic spiropyran
      containing peptides has been firstly established for detection of protein kinase
      A-catalyzed phosphorylation. The alternative method has advantages that avoid
      isolation and/or immobilization of kinase substrates to remove excess reagents
      including nonreactive isotope-labeled ATP or fluorescently-labeled anti
      phosphoamino acid antibodies from the reaction mixture. Such a novel protocol
      based on thermocoloration of the spiropyran moiety in the peptide can offer not
      only an efficient screening method of potent kinase substrates but also a
      versatile analytical tool for monitoring other post-translational modification
      activities.

PMID- 15745832
TI  - Further studies on ethenyl and ethynyl-4-phenylamino-3-quinolinecarbonitriles:
      identification of a subnanomolar Src kinase inhibitor.
AB  - Several new ethynyl- and ethenyl-4-phenylamino-3-quinolinecarbonitriles were
      synthesized and tested for Src inhibition. Derivatives bearing an ethenyl or
      ethynyl substituent at C-6 showed decreased Src inhibitory activity.
      Incorporation of an ethenylpyridine N-oxide group at C-7 provided 20b, a 0.6 nM
      inhibitor of Src enzymatic activity with excellent cellular potency.

PMID- 15745834
TI  - A novel polymorphism in the 5' flanking region of the glucose transporter (GLUT1)
      gene is strongly associated with diabetic nephropathy in patients with Type 1
      diabetes mellitus.
AB  - Glucose transporter 1 (GLUT1) activity has been implicated in renal hypertrophy
      and extracellular matrix formation in mesangial cells. Recent studies have
      suggested that polymorphisms in the GLUT1 gene are associated with susceptibility
      to diabetic nephropathy (DN) in patients with diabetes mellitus. In this study, a
      novel polymorphism (A-2841T) in the 5' flanking region of GLUT1 was examined in
      288 patients with Type 1 diabetes mellitus (T1DM) and 101 normal controls. The
      polymorphisms were amplified and the fragment digested with the enzyme HpyCH4V.
      There was a highly significant increase in the frequency of the TT-2841 genotype
      in patients with nephropathy (n=131) compared with those with either no
      microvascular complications after a 20-year duration of diabetes (uncomplicated;
      n=72; 54.5% vs. 2.7%, chi=79.4, P<.000001). There was no difference between the
      uncomplicated group and those who only had retinopathy (n=50; 2.7% vs. 4.0%,
      respectively). The frequency in recently diagnosed patients was 17.1% and only
      2.0% in normal controls. In contrast, the AA genotype was found in 13.6% of the
      nephropaths, 76.3% of uncomplicated, 48.0% of retinopaths, and 65% of normal
      controls. These results confirm previous reports of an association between the
      GLUT1 gene and susceptibility to DN but not retinopathy. The localisation of this
      polymorphism suggests that it may be involved in the expression of the gene.

PMID- 15745833
TI  - Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists.
AB  - The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH
      2), also found on eosinophils and basophils, is a prostaglandin D2 receptor
      involved in the recruitment of these cell types during an inflammatory response.
      In this report, we describe the synthesis and optimization of a ramatroban
      isostere that is a selective and potent antagonist of CRTH-2 which may be useful
      in the treatment of certain diseases.

PMID- 15745835
TI  - Aldose reductase (AC)n gene polymorphism and susceptibility to diabetic
      retinopathy in Type 2 diabetes in Caucasians.
AB  - Genetic factors are implicated in the development of diabetic retinopathy, and
      the aldose reductase (AC)n gene is a candidate gene for the development of
      diabetic retinopathy in patients with Type 2 diabetes. In the association study,
      a relationship between the aldose reductase (AC)n gene polymorphism and the
      development of diabetic retinopathy in patients with Type 2 diabetes were
      studied. We tested the hypothesis whether the Z-2 allele of the aldose reductase
      gene is a risk factor for the development of diabetic retinopathy in a group of
      Caucasian participants with Type 2 diabetes. Two hundred and five participants
      with Type 2 diabetes were enrolled in the study: 124 participants with Type 2
      diabetes with diabetic retinopathy were compared with 81 diabetic participants
      without retinopathy with diabetes duration of more than 10 years. Eight alleles
      of the aldose reductase (AC)n gene polymorphism were detected: Z+6, Z+4, Z+2, Z,
      Z-2, Z-4, Z-6, and Z-8. An increased frequency of the Z-2 allele was found in the
      patients with diabetic retinopathy compared with the patients without diabetic
      retinopathy (39.1% vs. 26.5%; P value=.009, chi2=6.9). Our results suggest that
      the Z-2 allele of the aldose reductase gene is a risk factor for the development
      of diabetic retinopathy in a group of Caucasian participants with Type 2
      diabetes.

PMID- 15745836
TI  - The rationale and design of the Glycemic Effects in Diabetes Mellitus Carvedilol
      Metoprolol Comparison in Hypertensives (GEMINI) trial.
AB  - Beta-blockers utilized in the Type 2 diabetic patient result in an even greater
      decrease in cardiac events than in the nondiabetic patient. Unfortunately, first
      and second-generation beta-blockers are associated with the worsening of insulin
      resistance, deterioration of glycemic control, peripheral vasoconstriction,
      potentially worsening peripheral vascular disease, and more frequent and severe
      hypoglycemia. The third-generation beta-blockers have unique properties,
      including alpha1-blockade, and have been shown to lower insulin resistance,
      improve glycemic control, and vasodilate resistance arterioles. The Glycemic
      Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives
      (GEMINI) trial has been designed to compare a third-generation (carvedilol) with
      a second-generation beta-blocker (metoprolol) in a cohort of participants with
      hypertension and Type 2 diabetes. The primary outcome measure of the study is
      change in the HbA1c. The study is powered to detect a difference in HbA1c of 0.3
      units (%) between the groups. Secondary endpoints include changes in insulin
      resistance, fasting glucose, and the lipid profile. Differences in the side
      effect profile (cold extremities, fatigue, impotence, and hypoglycemia) will also
      be assessed. The GEMINI trial, therefore, is the first large randomized trial to
      assess whether utilizing a third-generation beta-blocker yields a favorable
      metabolic profile in the patient with Type 2 diabetes and hypertension.

PMID- 15745838
TI  - Subjective well-being before and after the onset of diabetes mellitus: results of
      the Nord-Trondelag Health Study.
AB  - Previous research has documented that people with diabetes mellitus report lower
      psychological well-being than do people with no reported disease. Very little
      empirical evidence is available to support the conclusion that the low well-being
      is a consequence of diabetes per se. In this article, we analysed changes in
      psychological well-being among people who developed diabetes between 1984-1986
      and 1995-1997. On these two occasions, the entire adult population of one county
      in Norway was invited to health screenings (the Nord-Trondelag Health Studies,
      HUNT 1 and HUNT 2). The participants were 77,224 (90.7%) in HUNT 1 and 65,599
      (71.0%) in HUNT 2. A total of 46,320 people participated in both studies and were
      included in the analyses. The participation rate at HUNT 2 was lower among people
      with diabetes at HUNT 2 than among people without diabetes. The participants
      responded to questionnaires, including questions on several diseases, as well as
      self-assessed health and psychological well-being. In this article, the question
      is raised whether people who developed diabetes in the period between HUNT 1 and
      HUNT 2 reported lower well-being than people who did not. The analyses show that
      they did, but the differences were small, except for reported subjective health
      and vigor. Moreover, we found that people who reported diabetes in HUNT 2 but not
      in HUNT 1 reported lower well-being and more comorbidity, already in HUNT 1. They
      also reported a slight decline in well-being in the period, that is, poorer
      subjectively judged health and life satisfaction, less vigor and cheerfulness,
      and more use of tranquilizers than before they received the diabetes diagnosis.

PMID- 15745837
TI  - Hyperglycemia and its effect after acute myocardial infarction on cardiovascular
      outcomes in patients with Type 2 diabetes mellitus (HEART2D) Study design.
AB  - OBJECTIVE: Cardiovascular (CV) disease is the major cause of death in patients
      with diabetes. Up to 40% of patients with Type 2 diabetes mellitus (T2DM) who
      survive an initial myocardial infarction (MI) suffer a recurrent event within 2
      years, the majority of which are fatal. One independent risk factor for
      cardiovascular disease (CVD) may be postprandial blood glucose (PPBG) excursions.
      The HEART2D study seeks to determine the effect that PPBG control has on
      cardiovascular outcomes in patients who suffered an MI within the 21 days before
      study enrollment. RESEARCH DESIGN AND METHODS: Approximately 1355 patients with
      T2DM with recent MI will be entered in this multicenter study of about 3.0-year
      duration. Using infarct severity and peri-infarct treatment as randomization
      factors, patients will be assigned to one of two insulin treatment strategies:
      (1) postprandial strategy: premeal insulin lispro with basal insulin at bedtime
      if needed (NPH insulin), targeting 2-h PPBG < or = 7.5 mmol/l or (2) basal
      strategy: insulin (NPH insulin twice daily or insulin glargine once daily; or
      premixed human insulin (70% NPH/30% regular; 30/70) twice daily), targeting
      fasting and premeal blood glucose (BG; < or = 6.7 mmol/l). Both groups will aim
      for a target hemoglobin AlC (AlC) of < 7%. ANTICIPATED RESULTS: The anticipated
      difference in PPBG (approximately 2.0 to 2.5 mM) between strategies is expected
      to demonstrate a 15% to 18.5% relative risk reduction in CV events for the
      postprandial strategy. CONCLUSION: This study may provide practical insights into
      the clinical management of patients with diabetes who have an increased risk of
      recurrent CV events and death.

PMID- 15745839
TI  - Ascorbic acid and uric acid suppress glucose-induced fibronectin and vascular
      endothelial growth factor production in human endothelial cells.
AB  - Human umbilical vein endothelial cells (HUVECs) were used to investigate the
      individual effect of ascorbic (0.01 and 0.05 mM) and uric acid (3, 5, and 7
      mg/dl), as well as the combined effect of these two agents on glucose-induced
      overexpression of fibronectin (Fn), glutathione peroxidase (GPx) activity, H2O2
      level and vascular endothelial growth factor (VEGF) protein levels. Under 30 mM
      glucose stress, GPx activity significantly decreased, and lactate dehydrogenase
      (LDH) release, H2O2 level, and Fn and VEGF production significantly increased in
      HUVECs (P<.05). The addition of ascorbic acid at 0.05 mM or uric acid at 5 and 7
      mg/dl significantly reduced LDH release, recovered GPx activity, suppressed H2O2
      production, and decreased Fn and VEGF production (P<.05). The combination of 0.05
      mM ascorbic acid and 3, 5, or 7 mg/dl provided significantly greater effect in
      enhancing GPx activity and lowering H2O2 level than ascorbic acid or uric acid
      treatment alone did (P<.05). These data suggest that ascorbic acid alone or
      combined with uric acid in these concentrations may be beneficial to ameliorate
      glucose-induced diabetic deterioration.

PMID- 15745840
TI  - Diabetes-related comorbidities in Asian Americans: results of a national health
      survey.
AB  - OBJECTIVE: The aim of this study was to compare the prevalence of diabetes
      related comorbidities in Asian Americans to the prevalence in other racial and
      ethnic groups in the United States using data from the 2001 Behavioral Risk
      Factor Surveillance System (BRFSS). METHODS: The BRFSS is a population-based
      telephone survey of the health status and health behaviors of 212,510 Americans
      aged > or = 18 years in all 50 states, Guam, Puerto Rico, and the U.S. Virgin
      Islands. In 2001, participants included 196 Asian Americans, 1138 African
      Americans, 1276 Hispanics, 294 Native Americans, 71 Pacific Islanders, and 7799
      non-Hispanic Whites with a self-reported physician diagnosis of diabetes.
      Comorbidity was determined by self-report. Odds ratios (OR) were adjusted for
      age, sex, body mass index (BMI) or height and weight, duration of diabetes,
      smoking, and health-insurance status. RESULTS: The adjusted prevalences of
      hypercholesterolemia and retinopathy were similar across groups. Relative to
      Asian Americans, only African Americans were more likely to report hypertension
      [adjusted OR=2.1, 95% confidence interval (CI)=1.0-4.2, P<.05]. Higher odds of
      current or past foot ulceration was observed for Hispanics (adjusted OR=2.8, 95%
      CI=1.2-6.9), Native Americans (adjusted OR=4.2, 95% CI=1.4-12.8), and Pacific
      Islanders (adjusted OR=7.4, 95% CI=1.3-41.2) compared with Asian Americans.
      CONCLUSIONS: Among Americans with diabetes, Asian Americans have a prevalence of
      hypertension, hypercholesterolemia, retinopathy, and foot ulceration that is
      similar to that in Whites. Asian Americans had a significantly lower prevalence
      of hypertension than African Americans did and a lower prevalence of foot
      ulceration than Hispanics, Native Americans, and Pacific Islanders did.

PMID- 15745841
TI  - Diabetic lower extremity infection: influence of physical, psychological, and
      social factors.
AB  - AIMS: Although literature is scarce, it is a common belief that patients with
      lower social background are more prone to diabetic complications. The purpose of
      this study was to identify local, systemic, and psychosocial risk factors that
      can lead to severe foot infections and subsequent amputations. METHODS: This
      study was set up as a case-control study. We enrolled 112 persons with diabetes,
      in an approximately 1:1 case to control ratio. Cases were defined as patients
      admitted to the hospital with a severe foot infection, possibly necessitating a
      lower extremity amputation; controls were patients admitted for nonemergent
      medical or surgical cause. Study participants received a physical examination and
      interview to evaluate exposure variables, including demographic data, general
      medical, surgical, diabetes, and diabetes-related complication history.
      Socioeconomic status was quantified with the Duncan socioeconomic impact and
      Siegel prestige score. The patient's knowledge of foot care was evaluated as
      well. The risks for severe foot infection of social, economical, and physical
      risk factors were compared in a stepwise logistic regression analysis. RESULTS:
      The following variables were significant factors for severe foot infection:
      history of previous amputation [odds ratio (OR)=19.9, P=.01], peripheral vascular
      disease (OR=5.5, P=.007), and peripheral neuropathy, as measured with vibratory
      perception threshold (OR 3.4, P=.044). Social and economic factors were not
      significant in this model. CONCLUSIONS: These data suggest that physical risk
      factors are important in foot infection and that the additional risk of
      socioeconomic status or knowledge of foot care is limited in this population.

PMID- 15745842
TI  - Depression in diabetic patients: the relationship between mood and glycemic
      control.
AB  - PROBLEM: Evidence from prospective and cross-sectional studies demonstrates that
      the presence of diabetes doubles the risk of comorbid depression. This commonly
      overlooked comorbidity affects more than one quarter of the diabetic population,
      making its recognition and treatment in diabetic patients clinically relevant.
      METHODS: PubMed, PsycINFO, and MEDLINE databases were searched (search words:
      diabetes, depression, metabolic control, hyperglycemia, hypoglycemia) for
      articles that evaluated outcomes, relationships, and/or management of comorbid
      depression and diabetes published between 1980 and 2002. This review represents a
      synthesis of the findings including treatment recommendations. RESULTS:
      Concurrent depression is associated with a decrease in metabolic control, poor
      adherence to medication and diet regimens, a reduction in quality of life, and an
      increase in health care expenditures. In turn, poor metabolic control may
      exacerbate depression and diminish response to antidepressant regimens.
      Psychotherapy and pharmacotherapy are effective in the presence of diabetes; both
      cognitive behavior therapy and selective serotonin reuptake inhibitors are weight
      neutral and have been associated with glycemic improvement in some studies.
      CONCLUSION: Depression is common in both type 1 and type 2 diabetes and has
      significant effects on the course and outcome of this medical illness.
      Conventional antidepressant management strategies are effective and the regimen
      should be tailored to the individual patient. Enhanced efforts toward good
      glycemic control may also contribute to improvements in mood and perceptions of
      well-being.

PMID- 15745852
TI  - NTAL/LAB and LAT: a balancing act in mast-cell activation and function.

PMID- 15745853
TI  - Different faces of regulatory DCs in homeostasis and immunity.

PMID- 15745854
TI  - Dominant tolerance: activation thresholds for peripheral generation of regulatory
      T cells.

PMID- 15745855
TI  - CD69 is an immunoregulatory molecule induced following activation.

PMID- 15745856
TI  - Tails of wonder: endocytic-sorting motifs key for exogenous antigen presentation.
AB  - Antigen-presenting molecules, including MHC I, II and CD1, have central roles in
      the induction of T cell-mediated immunity against pathogens and tumors and also
      in the maintenance of tolerance towards self-antigens. The presentation of
      exogenously derived peptide and lipid antigens to specific T cells by
      professional antigen-presenting cells (pAPCs) is an essential part of both
      processes. Exogenous antigen loading takes place mostly within specialized
      endocytic and phagocytic compartments of pAPCs and targeting of antigen
      presenting molecules to these intracellular compartments is mediated by highly
      conserved cytoplasmic sorting motifs. Recent data have revealed that the
      cytoplasmic tails of antigen-presenting molecules, by controlling the access of
      these molecules to exogenously derived antigens, have a crucially important and
      largely underappreciated role in the generation of tolerance and T-cell mediated
      immunity.

PMID- 15745858
TI  - Transmigration through venular walls: a key regulator of leukocyte phenotype and
      function.
AB  - Leukocyte transmigration is a key event in host defense. As well as delivering
      leukocytes to sites of inflammation, this response also has an important role in
      immunity by regulating the responsiveness and behavior of leukocytes in the
      extravascular tissue. Recent evidence suggests that these events are associated
      with phenotypic and functional changes in migrating leukocytes mediated by
      signaling and transcriptional events triggered by the molecular interactions
      involved in leukocyte transendothelial cell migration. Transfer of membrane
      proteins from endothelial cells to migrating leukocytes and interaction of
      leukocytes with components of the perivascular basement membrane might also
      contribute to this effect. This Review will discuss the characteristics,
      potential mechanisms and the relevance of transmigration-induced change in
      leukocyte phenotype and responsiveness both within physiological and pathological
      scenarios.

PMID- 15745859
TI  - Immunodominance of HIV-1-specific CD8(+) T-cell responses in acute HIV-1
      infection: at the crossroads of viral and host genetics.
AB  - The development of HIV-1-specific CD8(+) T-cell responses during acute HIV-1
      infection is associated with a dramatic decline in HIV-1 replication and the
      resolution of the acute retroviral syndrome. These HIV-1-specific CD8(+) T cells
      typically target a small number of viral epitopes in a distinct hierarchical
      order, and high-level viremia in chronic progressive infection leads to broadly
      diversified HIV-1-specific CD8(+) T-cell responses with a less clear
      immunodominance pattern. It is argued here that the specific hierarchical pattern
      of immune responses in acute HIV-1 infection is the result of a tightly regulated
      process that, among other factors, is critically impacted by the kinetics of
      viral protein expression, the HLA class I background of the infected individual
      and the autologous sequence of the infecting virus.

PMID- 15745857
TI  - A stromal address code defined by fibroblasts.
AB  - To navigate into and within tissues, leukocytes require guidance cues that enable
      them to recognize which tissues to enter and which to avoid. Such cues are partly
      provided at the time of extravasation from blood by an endothelial address code
      on the luminal surface of the vascular endothelium. Here, we review the evidence
      that fibroblasts help define an additional stromal address code that directs
      leukocyte behaviour within tissues. We examine how this stromal code regulates
      site-specific leukocyte accumulation, differentiation and survival in a variety
      of physiological stromal niches, and how the aberrant expression of components of
      this code in the wrong tissue at the wrong time contributes to the persistence of
      chronic inflammatory diseases.

PMID- 15745860
TI  - IL-7: maintaining T-cell memory and achieving homeostasis.
AB  - During an immune response, peripheral T-cell populations expand and then contract
      as the response subsides, thus maintaining a fairly constant number of CD4 and
      CD8 T cells throughout the life of the individual. The important factors that
      control this homeostasis are now beginning to be understood. Interleukin-7 (IL-7)
      has emerged as a central regulator of the survival and homeostasis of CD4 and CD8
      T cells. Both naive and memory T-cell populations are highly dependent on the
      presence of IL-7 for their persistence and survival. In this Review, we discuss
      the role of IL-7 in the survival and homeostasis of naive and memory T cells and
      how that role is regulated by other factors.

PMID- 15745861
TI  - Differences in helping whites and blacks: a meta-analysis.
AB  - The amount of help given to Blacks versus Whites is often assumed to reflect
      underlying levels of racism (or lack thereof). This meta-analysis assessed
      discrimination against Blacks in helping studies. The overall effect size for the
      48 hypothesis tests did not show universal discrimination against Blacks (d =
      .03, p = .103). However, consistent with the predictions of aversive racism,
      discrimination against Blacks was more likely when participants could rationalize
      decisions not to help with reasons having nothing to do with race. Specifically,
      when helping was lengthier, riskier, more difficult, more effortful, and when
      potential helpers were further away from targets, less help was given to Blacks
      than to Whites. Interestingly, discrimination against Blacks was shown when there
      were higher levels of emergency. This suggests that discrimination may occur when
      the ability to control prejudicial responding is inhibited, or when the arousal
      of the emergency is misattributed to intergroup anxiety.

PMID- 15745862
TI  - Individualism: a valid and important dimension of cultural differences between
      nations.
AB  - Oyserman, Coon, and Kemmelmeier's (2002) meta-analysis suggested problems in the
      measurement of individualism and collectivism. Studies using Hofstede's
      individualism scores show little convergent validity with more recent measures of
      individualism and collectivism. We propose that the lack of convergent validity
      is due to national differences in response styles. Whereas Hofstede statistically
      controlled for response styles, Oyserman et al.'s meta-analysis relied on
      uncorrected ratings. Data from an international student survey demonstrated
      convergent validity between Hofstede's individualism dimension and horizontal
      individualism when response styles were statistically controlled, whereas
      uncorrected scores correlated highly with the individualism scores in Oyserman et
      al.'s meta-analysis. Uncorrected horizontal individualism scores and meta
      analytic individualism scores did not correlate significantly with nations'
      development, whereas corrected horizontal individualism scores and Hofstede's
      individualism dimension were significantly correlated with development. This
      pattern of results suggests that individualism is a valid construct for cross
      cultural comparisons, but that the measurement of this construct needs
      improvement.

PMID- 15745863
TI  - Social projection to ingroups and outgroups: a review and meta-analysis.
AB  - Social projection is the tendency to expect similarities between oneself and
      others. A review of the literature and a meta-analysis reveal that projection is
      stronger when people make judgments about ingroups than when they make judgments
      about outgroups. Analysis of moderator variables further reveals that ingroup
      projection is stronger for laboratory groups than for real social categories. The
      mode of analysis (i.e., nomothetic vs. idiographic) and the order of judgments
      (i.e., self or group judged first) have no discernable effects. Outgroup
      projection is positive, but small in size. Together, these findings support the
      view that projection can serve as an egocentric heuristic for inductive
      reasoning. The greater strength of ingroup projection can contribute to ingroup
      favoritism, perceptions of ingroup homogeneity, and cooperation with ingroup
      members.

PMID- 15745864
TI  - Social versus individual motivation: implications for normative definitions of
      religious orientation.
AB  - The traditional interpretation of "intrinsic" religiousness has fostered an
      unchallenged assumption that normative and substantive religious motivation is
      inherently individual and personal. Social motives for religiousness and
      structured practices have been characterized as "extrinsic" and as lacking in
      formative significance. We argue that this view is most applicable in American
      Protestant religions, and hence existing religious motivation scales reflect a
      distinctly American Protestant view. We then show that social motives and
      structured ritual practices are, in fact, as normative as individual motivations
      in several religious traditions. In particular, we describe the social practices
      and motives normative for Judaism and certain streams of Christianity. We then
      discuss the potential relevance of this analysis to emotion, collective identity,
      and moral judgment.

PMID- 15745865
TI  - Reconsidering evolved sex differences in jealousy: comment on Harris (2003).
AB  - In a recent article, Harris (2003) concluded that the data do not support the
      existence of evolved sex differences in jealousy. Harris' review correctly
      identifies fatal flaws in three lines of evidence (spousal abuse, homicide,
      morbid jealousy), but her criticism of two other lines of evidence (self-report
      responses, psychophysiological measures) is based, in part, on a
      mischaracterization of the evolutionary psychological theory and a
      misunderstanding of the empirical implications of the theory. When interpreted
      according to the correct criterion (i.e., an interaction between sex and
      infidelity type), self-report studies (both forced-choice and non-forced choice)
      offer strong support for the existence of sex differences in jealousy.
      Psychophysiological data also offer some support, although these data are
      weakened by validity-related concerns. In addition, some refutational evidence
      cited by Harris (responses to real infidelity, responses under cognitive load)
      actually does not refute the theory. An integrative model that describes how
      jealousy might result from the interaction of sociocultural variables and evolved
      sex differences and suggestions for future research directions are discussed.

PMID- 15745868
TI  - [Malaria in Haiti today].
AB  - Haiti is the only Caribbean island where malaria, practically always due to
      Plasmodium falciparum, persists in an epidemic-endemic state. In 1995 Haitian
      strains of P. falciparum were still sensitive to chloroquine. The principal
      vector is Anopheles albimanus, but the recent introduction in the south of Haiti
      of An. Pseudopunctipennis, which is an effective vector of P. falciparum in
      Central America, requires appropriate entomological surveillance. Essentially
      rural and seasonal, malaria is increasingly observed in the suburban areas around
      Port-au-Prince. The epidemiologic indicators have regressed since the 1980s and
      1990s. The plasmodic index in 1995 was low: 3.9%. Nonetheless imported malaria
      from Haiti presents a considerable threat to the other countries in the region
      because of the migrant flow. Updating data is essential to set up rational
      control strategies and appropriate advice to travellers.

PMID- 15745869
TI  - [Limits of the efficacy of chloroquine and sulfadoxine-pyrimethamine in Northern
      Abidjan (Cote d'Ivoire): Combined in vivo and in vitro studies].
AB  - Antimalarial drug resistance in endemic malaria zones is first detected in vitro;
      when it reaches a certain threshold, it becomes perceptible and is expressed in
      therapeutic failure among subjects only slightly or not at all immune. This work
      conducted in northern Abidjan (Cote d'Ivoire) studied children with uncomplicated
      malaria, who were followed for 14 days (during the year 2000) in accordance with
      the WHO protocol for surveillance of antimalarial drug resistance. Concomitantly,
      the Plasmodium falciparum isolates were cultured in the presence of variable
      concentrations of chloroquine, pyrimethamine and quinine during in vitro
      chemosensitivity tests. The RPMI 1640 used as medium for the pyrimethamine did
      not contain PABA (para-amino benzoic acid) or folic acid. In all, 114 in vitro
      tests were completed, 33 to chloroquine, 32 to pyrimethamine, and 49 to quinine.
      Therapeutic efficacy was tested in 65 patients: 33 to chloroquine and 32 to
      sulfadoxine-pyrimethamine (SP). The results found 36% of the isolates were
      chloroquine-resistant (CQ-R) and 33% of the patients treated with chloroquine did
      not respond adequately (therapeutic failure, TF). The 12 CQ-R isolates
      corresponded to 11 TF subjects and 1 patient with adequate clinical and
      parasitological response. The concordance between the two tests was good
      (kappa=0.93). For pyrimethamine, 37.5% of the isolates were resistant (PYR-R),
      and 37.5% of patients responded adequately to SP. The 12 PYR-R isolates were from
      12 TF subjects, so that kappa=1.0, when pyrimethamine resistance is defined as
      IC50 > 2,000 nM. Because of the elevated rate of chloroquine resistance, the
      national antimalaria program has recommended since July 2003 that amodiaquine be
      used as a first-line drug, to replace chloroquine. The relatively elevated number
      of TF with SP are a source of concern, because it is used in Yopougon (Abidjan).
      Additional studies to assess the prevalence of resistance to this combination in
      other areas of Abidjan city (Cote d' Ivoire) would be useful.

PMID- 15745870
TI  - [Infectious risks associated with blood exposure for traditional barbers and
      their customers in Morocco].
AB  - The trade of traditional barber has continued to expose its practitioners and
      their customers to multiple infectious diseases. The objective of this work was
      to study the infectious risk associated with blood exposure in this population
      and to assess its knowledge of this occupational risk. A cross-sectional
      epidemiologic survey was conducted in the Casablanca region during 2001 among 150
      barbers, all men. It included a medical-social questionnaire and a serology work
      up (HIV, HCV, HBV, TPHA, VDRL). The subjects' mean age was 36.5 years +/- 14.7,
      they had worked in the trade for an average of 17.8 years +/- 8.7, and the
      socioeconomic status of most was low. Hygiene conditions were deficient. The
      concept of infectious risk associated with blood was generally not well known,
      especially for hepatitis B and C; most were not vaccinated. HIV serology was
      negative for all barbers. On the other hand, syphilis serology was positive for
      7% by TPHA and for 4% by VDRL. HBV was positive in 2% and HCV in 5%. It is
      essential and urgent to promote awareness of these risks among all, especially
      the public authorities, and to formally ban barbers from the illegal practice of
      medicine for their own protection. All means of prevention must be used to
      protect the health of these workers and of the general population.

PMID- 15745872
TI  - [Healthcare demand in general practice facilities in the Tunisian Sahel].
AB  - This study of the reasons for consultations in primary healthcare facilities was
      intended to describe the practice of general medicine and to help develop a
      socially relevant curriculum for training family physicians. This descriptive and
      longitudinal survey was conducted at 6 such centres in Sousse, in the Tunisian
      Sahel, over a randomly chosen 30-day period during the year 2000. During this
      investigation, 6,576 reasons were reported for the 4,022 consultations included
      in the survey and were coded according to the International Classification of
      Primary Care (ICPC). The sex ratio of the consultants was 1:2 male:female and the
      median age was 27 years. Overall, respiratory illnesses were the leading motive
      for consultation, accounting for 36% of the visits. The "Top 20" list covered
      64.1% of the reasons reported. Coughing, sore throat, and fever occupied the top
      three positions, representing 13.5%, 11.6% and 7% of the reasons for
      consultation. Healthcare demand in these facilities thus reflected the extent of
      acute respiratory infections. This "Top 20" should be considered as a starting
      point for planning a valid medical curriculum.

PMID- 15745871
TI  - [Healthcare access in Benin: poverty and community aid networks].
AB  - The objective of this study was to evaluate the capacity of poor and non-poor
      households to pay for health care and to show how existing community assistance
      (or solidarity) networks (CAN) may compensate for this inability. Sixteen (16)
      study sites were randomly selected after stratification of Benin into four
      groups. All 1,312 households in our sample (668 poor and 664 non-poor) were
      interviewed, and 48 focus group were held with opinion leaders, women, healthcare
      workers, social workers, and persons responsible for these networks. The survey
      showed that only 27% of the heads of households have permanent financial access
      to health care and health services. This financial access is lower for the poor
      (9%) than for others (46%). However, the capacity of heads of households to pay
      reached 84% (87% for the non-poor and 81% for the poor, with P<0.01). Capacity to
      pay differs between strata (P<0.001) and is higher in the urban strata. For 25%
      of the families, intervention of the CAN made payment possible, preferentially
      for the poor. In 90% of cases, this community support came from the family
      network. Health centre management committees contributed in only 0.8% of cases.
      In general, help covered only a small percentage of those in need. The health
      policy of African countries must ensure that health care is accessible to the
      population, especially the poor.

PMID- 15745873
TI  - [Social and cultural determinants of dental health practices in Morocco: results
      of a qualitative study].
AB  - The objective of any health education program is to inculcate healthy life habits
      to improve the health status of the target population. The evaluation of an oral
      hygiene health education program for Moroccan schoolchildren implemented a decade
      ago by oral surgeons does not reveal any improvement of their dental health. To
      understand the obstacles to the acquisition of good oral hygiene habits, we
      conducted a qualitative survey of knowledge, attitude, and practices, based on
      semi-directive interviews with focus groups of children who had participated in
      the program. The results show that social and cultural determinants play an
      important role in the lack of impact of these programs and that Bourdieu's theory
      of action should be applied to understand the processes by which living
      conditions affect individuals'practices. Thus to inculcate healthy lifestyle
      habits, an ecological approach that takes into consideration the social,
      cultural, and economic environment is most likely to induce the emergence of
      favourable social conditions.

PMID- 15745874
TI  - [Epidemiology of eye injuries in Abidjanian children].
AB  - Eye injuries, most of them preventable, are particularly severe in Africa,
      because of the risks of infection and delay in treatment. We report a 16-month
      (March 1997-June 1998) prospective observational survey of eye injuries in
      children up to the age of 15 years at Treichville-Abidjan University Hospital.
      During this period, 62 children were treated for these injuries. Ocular traumas
      represented 4% (n = 245) of new admissions in ophthalmology, and 29% of these
      injuries occurred in children. The sex ratio was 5:2 boys to girls, and their
      mean age was 8.66 +/- 3.56 years. Eye injuries occurred most often during play
      (84%, n = 52). More than 85% (n = 53) of children were alone or without adult
      supervision at the time of the injury. The causal agent was most often wood (35%)
      followed by metal (29%). The mean time from injury to hospital admission was 1.8
      +/- 0.77 day. Only 19% of patients were admitted the day of injury. Most patients
      (66%) first sought treatment in a primary care centre. More than 70% (n = 44) of
      injuries necessitated hospitalisation. Open eyeball wounds were the most common
      injury (53%) and were associated with endophthalmitis in 16%. The mean recovery
      of visual acuity was 0.1. At admission, 40 of the injured eyes (64.5%) had
      monocular blindness; six recovered, for a final blindness rate of 55%. Injuries
      associated with wooden objects had a final blindness rate of 77% and play-related
      injuries 63%. The primary posttraumatic sequelae were corneal scars. Eyeball
      phthysis (14.5%) was secondary to 8 open wounds of the eyeball and one
      postcontusion retinal detachment. Eye injuries remain a major cause of monocular
      blindness in children in Cote d'Ivoire. Most of them can be prevented by
      relatively simple measures including supervision of children and rapid
      hospitalisation when injury occurs.

PMID- 15745876
TI  - [Assessment of partogram utilisation in Benin].
AB  - A safe motherhood program was launched in Benin in 1989. One of the methods used
      to decrease maternal mortality and morbidity was the partogram. We recently
      conducted a survey in maternity facilities in urban and rural Benin to assess its
      utilisation rate and the quality of its use. In this cross-sectional survey, all
      facilities were asked to respond to a questionnaire. In addition, we
      retrospectively studied files in half the facilities, based on a stratified
      randomisation. Partograms were used in 98% of all cases; in 13.3% of files (all
      in rural areas), partogram completion stopped before delivery. Overall completion
      was less good: of the 984 partograms examined, administrative data were complete
      on only 20% and medical delivery data on 50%. Action taken before the alert line
      was crossed was incorrect in 48% of cases (particularly oxytocin use). The alert
      line was crossed in 13.5% of the cases, but correct action always followed
      (artificial rupture of membranes, oxytocin administration). The patient transfer
      rate was 13% and the cesarean rate 5.2%. This alert line was crossed only once.
      These results thus show very high coverage of partogram use, but inadequate
      quality and thus demonstrate the need for refresher training for maternity staff
      about partogram use.

PMID- 15745875
TI  - [Improving the quality of care after spontaneous abortions in rural Senegal].
AB  - OBJECTIVES: To evaluate the feasibility and impact on quality of decentralising
      care for spontaneous abortion (post-abortion care, PAC) in rural areas of
      Senegal. PATIENTS AND METHOD: This prospective study concerns all patients who
      had PAC services at 6 medical centres in the districts of Kaolack and Fatick. A
      preintervention baseline study was performed to evaluate the number of cases
      treated in these centres. We then introduced a new treatment protocol for PAC,
      which included manual vacuum aspiration (MVA) and quarterly visits for
      supervision in each centre from 1 August 2001 through 30 September 2002. An
      evaluation was performed at the end of the program and 6 months after that.
      Results were compared with the baseline data for the 14 months before the
      intervention period. We used the chi(2) test to compare proportions and set the
      threshold of significance at 5%. RESULTS: The new model for PAC made it possible
      to increase the number of patients treated for incomplete abortion by 22%. Their
      average age was 25 years, and 71% had first-trimester pregnancy losses. MVA was
      performed for 56%. Hospitalisation lasted a mean of 4 hours compared with the 48
      hours at baseline, and the proportion of patients referred to the regional
      hospital for complications fell from 35% to 7%. The mean direct average cost fell
      by 3,500 F CFA. The number of patients with contraception in place before
      discharge rose from 0 to 20%, and 94% of the patients questioned were satisfied
      with the quality of the services they received. Six month after the program
      ended, the level of utilisation of PAC services continued to increase (by 11%)
      and the proportion leaving with contraception reached 33%. CONCLUSION:
      Decentralisation of PAC treatment in rural areas is possible without major
      expense, and it improves care for women with incomplete abortions.

PMID- 15745877
TI  - [Factitious lithiasis: Case report from Western Algeria].
AB  - A 19-year-old woman with recurrent lithiasis was admitted to the urology
      department for renal colic. Although radiologic examinations and laboratory tests
      were negative, the patient regularly brought into consultations small "stones",
      resembling gravel, that she said had been spontaneously expelled. These 42
      samples were the object of a preliminary morphological analysis under a binocular
      magnifier to detect their particulate components. A non-metabolic origin was
      suspected from the organoleptic characteristics of their surfaces and sections.
      In view of the diversity of the materials of these apparently false calculi,
      methods of precise physical analysis were necessary to ascertain their exact
      origin and thereby confirm the diagnosis of factitious lithiasis. The use of two
      methods of physical analysis, infrared spectrophotometry and x-ray diffraction,
      enabled us to determine their exact chemical and mineralogical composition. The
      samples claimed to be of urinary origin actually consisted of exogenous products
      of various compositions. Some samples were made of pure calcite, others of mixed
      calcite and silicates. Moreover several samples of the patient's first morning
      urine showed no correlation between the nature of the crystalluria and the
      composition of these stones. These tests made it possible to direct the clinician
      towards useful complementary investigations. This strange case represents 0.1% of
      the urinary calculi analysed in Western Algeria.

PMID- 15745878
TI  - [Familial Mediterranean Fever (FMF): from diagnosis to treatment].
AB  - Familial Mediterranean Fever (FMF), also known as paroxysmal polyserositis, is an
      autosomal recessive disease affecting mainly Mediterranean populations (Jews,
      Armenians, Arabs, Turks). It is characterised by recurrent crises of fever and
      serosal inflammation, leading to abdominal, thoracic or articular pain. Erysipela
      like erythema affecting mainly feet and legs and effort-induced myalgia are less
      frequently encountered symptoms. The major complication of FMF is the development
      of renal amyloidosis. Standard laboratory tests of FMF patients are non
      informative, except for the high sedimentation rate and white blood cell count,
      but during and immediately after crises, diminished albumin concentrations and
      elevated fibrinogen, C-reactive protein, beta2 and alpha2 M globulins,
      haptoglobin and lipoprotein concentrations are noted. Studies have measured
      immunoglobulin (Ig) levels in the sera of FMF patients and found elevated levels
      of IgA, IgM, IgG, and IgD in 23%, 13%, 17% and 13%, respectively. FMF crises are
      characterised by a massive influx of polymorphonuclear leukocytes into the
      inflamed regions. Moreover, the peritoneal fluid of FMF patients contains
      abnormally low levels of the inhibitor of complement fragment C5a and interleukin
      8. Failure to suppress inflammatory response to C5a may explain the typical
      inflammatory FMF crises. The MEFV (for MEditerranean FeVer) gene responsible for
      the disease has been identified on 16p13.3. It is composed of 10 exons and spans
      approximately 14 Kb of genomic DNA. More than 35 mutations have so far been
      identified. The most frequent are M694V, M694I, M680I, V726A and E148Q. The M694V
      mutation is the most frequent mutation in the various ethnic groups considered,
      although its frequency varies from group to group. The V726A mutation is observed
      mainly among Ashkenazi and Iraqi Jews, Druzes and Armenians, and the M680I among
      Armenians and Turks. M694I and A744S seem specific to Arab populations, and R761H
      is frequently found in Lebanese FMF patients. The M694V mutation is often
      correlated with severe phenotypes, mainly in the homozygous state. It has been
      specifically correlated with arthritis, pleuritis and especially amyloidosis.
      Patients with other mutations in the 694 and 680 codons can also have severe
      phenotypes. The V726A mutation, although identified in FMF patients with a
      relatively mild phenotype, has also been detected in patients with renal
      amyloidosis. E148Q is often associated with a mild phenotype, and whether it is
      even a polymorphism has been questioned. The MEFV gene codes for a protein that
      was respectively called pyrin and marenostrin by the French and international
      consortia that simultaneously identified the gene. Its function is still not
      determined, but it was recently colocalised with microtubules and actin filaments
      in the cytoplasm. It contains a death domain called PYD (Pyrin Domain), usually
      associated with proteins involved in apoptosis. Some genes have been tested to
      assess their possible modifying effects on clinical features of FMF. The
      alpha/alpha genotype of the serum amyloid A or SAA1 gene is associated with an
      increased risk of amyloidosis in FMF patients, especially in patients homozygous
      for M694V, whereas the MICA (Major Histocompatibility Complex, MHC class-I-chain
      related type A) gene seems to have an effect on disease course but not its
      clinical manifestations. The most effective treatment for FMF patients is
      colchicine, which should be taken regularly on a life-long basis. It decreases
      the frequency and severity of crises and prevents renal amyloidosis.

PMID- 15745880
TI  - Policymakers, experts review evidence-based medicine.

PMID- 15745881
TI  - Pharmacy helps hospital win national quality award.

PMID- 15745879
TI  - Phosducin-like protein regulates G-protein betagamma folding by interaction with
      tailless complex polypeptide-1alpha: dephosphorylation or splicing of PhLP turns
      the switch toward regulation of Gbetagamma folding.
AB  - Phosducin-like protein (PhLP) exists in two splice variants PhLP(LONG) (PhLP(L))
      and PhLP(SHORT) (PhLP(S)). Whereas PhLP(L) directly inhibits Gbetagamma
      stimulated signaling, the G betagamma-inhibitory mechanism of PhLP(S) is not
      understood. We report here that inhibition of Gbetagamma signaling in intact HEK
      cells by PhLP(S) was independent of direct Gbetagamma binding; however, PhLP(S)
      caused down-regulation of Gbeta and Ggamma proteins. The down-regulation was
      partially suppressed by lactacystine, indicating the involvement of proteasomal
      degradation. N-terminal fusion of Gbeta or Ggamma with a dye-labeling protein
      resulted in their stabilization against down-regulation by PhLP(S) but did not
      lead to a functional rescue. Moreover, in the presence of PhLP(S), stabilized
      Ggamma subunits did not coprecipitate with stabilized Gbeta subunits, suggesting
      that PhLP(S) might interfere with Gbetagamma folding. PhLP(S) and several
      truncated mutants of PhLP(S) interacted with the subunit tailless complex
      polypeptide-1alpha (TCP-1alpha) of the CCT chaperonin complex, which is involved
      in protein folding. Knock-down of TCP-1alpha in HEK cells by small interfering
      RNA also led to down-regulation of Gbetagamma. We therefore conclude that the
      strong inhibitory action of PhLP(S) on Gbetagamma signaling is the result of a
      previously unrecognized mechanism of Gbetagamma-regulation, inhibition of
      Gbetagamma-folding by interference with TCP-1alpha.

PMID- 15745882
TI  - New drug and biological product approvals, 2004.

PMID- 15745883
TI  - Humanistic-outcomes questionnaires in diabetes research and practice.

PMID- 15745884
TI  - Folic acid in alcohol-withdrawal delirium.

PMID- 15745885
TI  - Potential and perils of implantable microchip.

PMID- 15745886
TI  - Inaccessibility of online PDR to pharmacists.

PMID- 15745888
TI  - Counseling patients with low health literacy.

PMID- 15745887
TI  - Disclosing conflicts of interest involving clinicians who prepare therapeutic
      guidelines.

PMID- 15745889
TI  - Pharmacists' role in increasing pneumococcal and influenza vaccination.
AB  - PURPOSE: The role of the pharmacist in increasing pneumococcal and influenza
      vaccination rates and the clinical efficacy of pneumococcal and influenza
      vaccines are discussed. SUMMARY: Institutional pharmacists often play key roles
      on multidisciplinary committees and have the opportunity to make preventive
      therapies, such as vaccination, a priority. Standing-order programs authorize
      health care professionals to screen for vaccine eligibility and
      contraindications, administer vaccines, and monitor for adverse effects when
      following a physician- or institution-approved protocol. Current vaccination
      levels for the influenza and pneumococcal vaccines are suboptimal and well below
      the Healthy People 2010 goal of 90% of high-risk patients. Pharmacists should be
      familiar with the composition, immunogenicity, dosage, administration, efficacy,
      adverse reactions, contraindications, precautions, and cost-effectiveness of each
      vaccine, as well as with Advisory Committee on Immunization Practices
      recommendations and the supporting literature. CONCLUSION: Health-system
      pharmacists have the opportunity and responsibility to protect those at highest
      risk of pneumococcal disease and influenza through the use of standing-order
      vaccination programs.

PMID- 15745890
TI  - ASHP national survey of pharmacy practice in hospital settings: prescribing and
      transcribing--2004.
AB  - PURPOSE: Results of the 2004 ASHP national survey of pharmacy practice in
      hospital settings that pertain to prescribing and transcribing are presented.
      METHODS: A stratified random sample of pharmacy directors at 1183 general and
      children's medical-surgical hospitals in the United States was surveyed by mail.
      SMG Marketing Group, Inc., supplied data on hospital characteristics; the survey
      sample was drawn from SMG's hospital database. RESULTS: The response rate was
      41.7%. Compared with the results of the 2001 survey, the number of times pharmacy
      and therapeutics committees met increased, suggesting an increase in efforts to
      monitor and manage medication use in hospitals. There was an increase in the use
      of quality-of-life information to make formulary decisions, indicating a shift
      away from cost-based formularies. There was a decrease in the rates of formulary
      compliance, but an increase in the use of evidence-based clinical practice
      guidelines, suggesting the emergence of more comprehensive approaches to
      improving prescribing. The use of medication-use evaluations increased in smaller
      hospitals, suggesting greater use of best practices is occurring in these
      institutions. The use of drug information services continues to decline, as the
      use of more efficient and easily accessible online sources of drug information
      increases. Reading back oral orders to improve accuracy dramatically increased
      since 2001. The adoption of computerized prescriber-order-entry systems continues
      to be slow, with fewer than 5% of hospitals reporting their use. CONCLUSION: The
      2004 ASHP survey results indicate that pharmacists are continuing to improve
      medication use at the prescribing and transcribing steps of the medication-use
      system.

PMID- 15745891
TI  - Cyclosporine-sparing effects of daclizumab in renal allograft recipients.
AB  - PURPOSE: The safety and efficacy of reduced-dose cyclosporine in renal
      transplantation were studied. METHODS: Patients receiving their first renal
      transplant received daclizumab 1 mg/kg every 14 days for a total of five doses,
      mycophenolate mofetil 1 g twice daily, corticosteroids per the institution's
      routine protocol, and half of the institution's usual cyclosporine dosage. Trough
      cyclosporine concentrations targeted were half the customary goals, or 150-200
      ng/mL for the first six months and 125-175 ng/mL for months 7-12. A retrospective
      control group included 15 matched patients who had received full-dose
      cyclosporine, mycophenolate mofetil, and corticosteroids without daclizumab
      induction therapy. RESULTS: Thirty patients were studied (15 in each group). At
      baseline, the control group had a significantly lower panel reactive antibody
      level (0.13%) than the treatment group (5.2%) (p = 0.01). Mean cyclosporine
      concentrations at 1, 6, and 12 months were significantly lower in the treatment
      group (p < 0.0001). No patient in either group had an acute rejection episode.
      All control patients had cyclosporine-associated adverse effects, compared with
      seven treatment-group patients (p = 0.0022). The treatment group had 19
      infections, versus 29 in the control group (p = 0.39). Three study-group patients
      and eight control patients required a fine-needle aspiration or biopsy (p =
      0.13). CONCLUSION: Among kidney transplant patients at low risk of acute
      rejection, those treated with daclizumab and low-dose cyclosporine had an
      identical rate of acute rejection (none) and fewer cyclosporine-associated
      adverse effects compared with patients in a retrospective control group who
      received full-dose cyclosporine without daclizumab.